PMID- 25938550
TI  - Setting up a Nuchal Translucency Clinic: What Radiologists Need to Know.
AB  - The purpose of this article was to discuss the process of setting up a nuchal
      translucency (NT) screening clinic in clinical practice, how to interpret the
      information in combination with other clinical tests, what to do if abnormal
      results are obtained, and to illustrate some of the fetal anomalies that are
      associated with an increased NT. The NT was initially implemented to predict the
      likelihood of a fetus with Down syndrome. Maternal age can be combined with fetal
      NT and maternal serum biochemistry (free beta-hCG and PAPP-A) at 11 to 14 weeks
      to identify about 90% of affected fetuses. Setting up a clinic to perform the NT
      screening requires certified physicians and certified sonographers. Certification
      can be obtained for both physicians and sonographers through Nuchal Translucency
      Quality Review and Fetal Medicine Foundation. Cell-free DNA testing is now
      altering what our patients are choosing to evaluate fetuses at risk for
      chromosomal anomalies and congenital anomalies. Common pitfalls to performing,
      interpreting, and conveying results of the NT are illustrated in this article.
      Nasal bone measurement, fetal anatomy examination and fetal echocardiography are
      tools that add sensitivity to the detection of chromosomal abnormalities.
      Examples of fetal anomalies discovered during the NT screening are also
      illustrated. Screening for obstetric complications is an additional benefit to
      the NT clinic. 

PMID- 25938552
TI  - Correction: harnessing soluble NK cell killer receptors for the generation of
      novel cancer immune therapy.

PMID- 25938551
TI  - Both MicroRNA-155 and Virus-Encoded MiR-155 Ortholog Regulate TLR3 Expression.
AB  - MicroRNA-155 (miR-155) has been as an important controller of TLR3 signalling.
      However, the interactions between miR-155 and TLR3 are poorly understood. Here,
      we focused on the regulation of the relationship between miR-155 and TLR3.
      Sequence analyses and firefly luciferase reporter assay revealed that miR-155
      target were present in the coding sequences (CDS) of TLR3. And the expression of
      the TLR3 protein could be inhibited by a miR-155 mimic or by a virally encoded
      orthologue in chick embryo fibroblast cells. Notably, endogenous miR-155
      induction emerged a negative regulation on TLR3 expression in TLR2, 4 and 7
      ligands stimulated HD11 cells, an avian macrophage cell line. Moreover, treatment
      with the miR-155 antagomir increased TLR3 levels while significantly decreased
      the abundance of TLR3 with miR-155 agomir. In addition, our data showed that miR
      155 could inhibit IFN-beta production possibly though TLR3 signal pathway. All
      these findings might reveal a new mechanism by which miR-155 can regulate the
      TLR3 immune response. 

PMID- 25938553
TI  - Dispositional optimism and terminal decline in global quality of life.
AB  - We examined whether dispositional optimism relates to change in global quality of
      life (QOL) as a function of either chronological age or years to impending death.
      We used a sample of 2,096 deceased postmenopausal women from the Women's Health
      Initiative clinical trials who were enrolled in the 2005-2010 Extension Study and
      for whom at least 1 global QOL and optimism measure were analyzed. Growth curve
      models were examined. Competing models were contrasted using model fit criteria.
      On average, levels of global QOL decreased with both higher age and closer
      proximity to death (e.g., M(score) = 7.7 eight years prior to death vs. M(score)
      = 6.1 one year prior to death). A decline in global QOL was better modeled as a
      function of distance to death (DtD) than as a function of chronological age
      (Bayesian information criterion [BIC](DtD) = 22,964.8 vs. BIC(age) = 23,322.6).
      Optimism was a significant correlate of both linear (estimate(DtD) = -0.01,
      SE(DtD) = 0.005; rho = 0.004) and quadratic (estimate(DtD) = -0.006, SE(DtD) =
      0.002; rho = 0.004) terminal decline in global QOL so that death-related decline
      in global QOL was steeper among those with a high level of optimism than those
      with a low level of optimism. We found that dispositional optimism helps to
      maintain positive psychological perspective in the face of age-related decline.
      Optimists maintain higher QOL compared with pessimists when death-related
      trajectories were considered; however, the gap between those with high optimism
      and those with low optimism progressively attenuated with closer proximity to
      death, to the point that is became nonsignificant at the time of death.

PMID- 25938554
TI  - Oral narrative skills: Explaining the language-emergent literacy link by
      race/ethnicity and SES.
AB  - Although children's early language skills have been found to predict literacy
      outcomes, little is known about the role of preschool oral narrative skills in
      the pathway between language and emergent literacy or how these associations
      differ by race/ethnicity and socioeconomic status. The current study uses the
      Early Childhood Longitudinal Study to explore how language at age 2 is associated
      with narrative skills at age 4 and emergent literacy outcomes at age 5 for a
      nationally representative sample of children. Findings demonstrate that early
      language is associated with narrative skills for most children. Oral narrative
      skills were found to mediate the pathway between early language and kindergarten
      emergent literacy for poor and nonpoor African American children. Implications
      for children's literacy development and future research are discussed.

PMID- 25938555
TI  - Positive emotional engagement and autism risk.
AB  - Positive emotional engagement develops in the context of face-to-face
      interactions during the first 6 months of life. Deficits in emotional engagement
      are characteristic of autism spectrum disorder (ASD) and may characterize the
      younger siblings of children with ASD (high-risk siblings). High-risk siblings
      are likely to exhibit a broad range of positive emotional engagement that may or
      may not be associated with ASD outcomes. We examined positive emotional
      engagement (i.e., smiling rate and contingent responsiveness to the partner's
      smile) during the infant-parent interaction episodes of the face-to-face/still
      face protocol at 6 months of age. The sample included 43 high-risk infant
      siblings, 11 of whom went on to an ASD diagnosis, and 25 low-risk siblings with
      no family history of ASD. Low-risk siblings and high-risk siblings without ASD
      showed the typical still-face effect (i.e., decreases in smiling rate after
      period of parental nonresponsiveness), but high-risk siblings with later ASD
      outcomes did not show this decrease. Although high-risk siblings without an ASD
      diagnosis were less likely to respond to their parents' smiles than were low-risk
      siblings, the children with eventual ASD did not differ from the other groups in
      contingent responsiveness. Findings suggest that subtle differences in positive
      emotional engagement are present in the early development of high-risk siblings
      but are not consistently associated with ASD outcomes.

PMID- 25938556
TI  - Anisamide-Decorated pH-Sensitive Degradable Chimaeric Polymersomes Mediate Potent
      and Targeted Protein Delivery to Lung Cancer Cells.
AB  - In spite of their high potency and specificity, few protein drugs have advanced
      to the clinical settings due to lack of safe and efficient delivery vehicles.
      Here, novel anisamide-decorated pH-sensitive degradable chimaeric polymersomes
      (Anis-CPs) were designed, prepared, and investigated for efficient and targeted
      delivery of apoptotic protein, granzyme B (GrB), to lung cancer cells. Anis-CPs
      were readily prepared with varying Anis surface densities from anisamide end
      capped poly(ethylene glycol)-b-poly(2,4,6- trimethoxybenzylidene-1,1,1
      tris(hydroxymethyl)ethane methacrylate)-b-poly(acrylic acid) (Anis-PEG-PTTMA-PAA)
      and PEG-PTTMA-PAA copolymers. Using cytochrome C (CC) as a model protein, Anis
      CPs displayed high protein loading efficiencies (40.5-100%) and loading contents
      (up to 16.8 wt %). CC-loaded Anis-CPs had narrow distribution (PDI 0.04-0.13) and
      small sizes ranging from 152 to 171 nm, which increased with increasing CC
      contents. Notably, the release of proteins from Anis-CPs was accelerated under
      mildly acidic conditions, due to the hydrolysis of acetal bonds in PTTMA. MTT
      assays showed that GrB-loaded Anis-CPs (GrB-Anis-CPs) displayed high
      targetability to sigma receptor overexpressing cancer cells such as H460 and PC-3
      cells. For example, GrB-Anis-CPs exhibited increasing antitumor efficacy to H460
      cells with increasing Anis contents from 0 to 80%. The antitumor activity of GrB
      Anis-CPs was significantly reduced upon pretreating H460 cells with haloperidol
      (a competitive antagonist). Notably, the half-maximal inhibitory concentrations
      (IC50) of GrB-Anis70-CPs were determined to be 6.25 and 5.94 nM for H460 and PC-3
      cells, respectively, which were 2-3 orders of magnitude lower than that of
      chemotherapeutic drugs, such as paclitaxel. Flow cytometry studies demonstrated
      that GrB-Anis70-CPs induced widespread apoptosis of H460 cells. The confocal
      laser scanning microscopy (CLSM) experiments using FITC-labeled CC-loaded Anis
      CPs confirmed fast internalization and intracellular protein release into H460
      cells. GrB-Anis-CPs with high potency and specificity are particularly
      interesting for targeted therapy of lung cancers.

PMID- 25938557
TI  - Confluence-Induced Squamous Differentiation Is Not Accompanied by Changes in
      H3K27me3 Repressive Epigenetic Mark.
AB  - Recent studies have reported that epigenetic mechanisms may regulate the
      initiation and progress of squamous differentiation in normal and transformed
      keratinocytes. In particular, the role of the repressive H3K27me3 mark in the
      regulation of squamous differentiation has been prominent. However, there is
      conflicting literature showing that squamous differentiation may be dependent
      upon or independent of changes in H3K27me3 status. In this study we have examined
      the binding of trimethylated H3K27 to the promoters of proliferation or
      differentiation genes in keratinocytes undergoing squamous differentiation in
      vitro and in vivo. Initially, we examined the expression levels for EZH1, EZH2,
      and H3K27me3 in differentiating keratinocytes in vitro and in vivo. We extended
      this to include H3K27me3 chromatin immunoprecipitation sequencing (ChIP-seq).
      Based on these studies, we could find no evidence for an association between
      widespread gain or loss of H3K27me3 on the promoters of proliferation-specific or
      differentiation-specific target genes, respectively, during squamous
      differentiation in adult human keratinocytes. These data suggest that squamous
      differentiation may occur independent of regulation by H3K27me3 on proliferation
      and differentiation genes of normal adult human keratinocytes. 

PMID- 25938558
TI  - Inhibition of EGFR Tyrosine Kinase by Erlotinib Prevents Sclerodermatous Graft
      Versus-Host Disease in a Mouse Model.
AB  - Chronic graft-versus-host disease (GVHD) follows allogeneic hematopoietic stem
      cell transplantation. It results from alloreactive processes induced by minor
      histocompatibility antigen incompatibilities leading to the activation of CD4 T
      cells and the development of fibrosis and inflammation of the skin and visceral
      organs and autoimmunity that resemble systemic sclerosis. EGFR is a ubiquitous
      cell receptor deeply involved in cell proliferation, differentiation, and
      motility. EGFR has recently been implicated in autoimmune and fibrotic diseases.
      Therefore, we tested whether Erlotinib, an EGFR tyrosine kinase inhibitor, can
      prevent sclerodermatous GVHD (Scl-GVHD). Scl-GVHD was induced in BALB/c mice by
      B10.D2 bone marrow and spleen cell transplantation. Transplanted mice displayed
      severe clinical symptoms including alopecia, fibrosis of the skin and visceral
      organs, vasculitis, and diarrhea. The symptoms were reversed in mice treated with
      Erlotinib. These beneficial effects were mediated by the decreased production of
      activated/memory CD4(+) T cells and the reduction in T-cell infiltration of the
      skin and visceral organs along with a decrease in IFN-gamma and IL-13 production
      and autoimmune B-cell activation. The improvement provided by Erlotinib in the
      mouse model of Scl-GVHD supplies a rationale for the evaluation of Erlotinib in
      the management of patients affected by chronic GVHD. 

PMID- 25938559
TI  - Juxtacellular Monitoring and Localization of Single Neurons within Sub-cortical
      Brain Structures of Alert, Head-restrained Rats.
AB  - There are a variety of techniques to monitor extracellular activity of single
      neuronal units. However, monitoring this activity from deep brain structures in
      behaving animals remains a technical challenge, especially if the structures must
      be targeted stereotaxically. This protocol describes convenient surgical and
      electrophysiological techniques that maintain the animal's head in the
      stereotaxic plane and unambiguously isolate the spiking activity of single
      neurons. The protocol combines head restraint of alert rodents, juxtacellular
      monitoring with micropipette electrodes, and iontophoretic dye injection to
      identify the neuron location in post-hoc histology. While each of these
      techniques is in itself well-established, the protocol focuses on the specifics
      of their combined use in a single experiment. These neurophysiological and
      neuroanatomical techniques are combined with behavioral monitoring. In the
      present example, the combined techniques are used to determine how self-generated
      vibrissa movements are encoded in the activity of neurons within the
      somatosensory thalamus. More generally, it is straightforward to adapt this
      protocol to monitor neuronal activity in conjunction with a variety of behavioral
      tasks in rats, mice, and other animals. Critically, the combination of these
      methods allows the experimenter to directly relate anatomically-identified
      neurophysiological signals to behavior. 

PMID- 25938560
TI  - Induction of Energy Expenditure by Sitagliptin Is Dependent on GLP-1 Receptor.
AB  - Sitagliptin (SG) increases serum GLP-1 (Glucagon-like peptide-1) through
      inhibition of the hormone degradation. Resistant starch (RS) induces GLP-1
      expression by stimulating L-cells in the intestine. Sitagliptin and resistant
      starch may have a synergistic interaction in the induction of GLP-1. This
      possibility was tested in current study in a mouse model of type 2 diabetes.
      Hyperglycemia was induced in the diet-induced obese mice by a signal injection of
      streptozotocin (STZ). Sitagliptin (0.4g/100g diet) was tested in the mice (n =
      55) with dietary RS (HAM-RS2) at three dosages (0, 15, or 28g/100g diet). Energy
      and glucose metabolism were monitored in the evaluation of synergistic activity,
      and GLP-1 activity was determined in the GLP-1 receptor knockout (KO) mice. In
      the wild type mice, body weight and adiposity were reduced by sitagliptin, which
      was enhanced by RS (28g). Serum GLP-1 was induced and energy expenditure was
      enhanced by sitagliptin. Fasting glucose, insulin, and leptin levels were
      decreased by sitagliptin. The sitagliptin effects were lost in the KO mice (n =
      25) although induction of serum GLP-1 by sitagliptin was even stronger in KO
      mice. The data suggests that sitagliptin is able to reduce adiposity and insulin
      resistance through induction of energy expenditure. The effect of sitagliptin is
      partially enhanced by RS. GLP-1 receptor may regulate serum GLP-1 by facilitating
      the hormone clearance. 

PMID- 25938562
TI  - Electrospun nanofiber scaffolds with gradations in fiber organization.
AB  - The goal of this protocol is to report a simple method for generating nanofiber
      scaffolds with gradations in fiber organization and test their possible
      applications in controlling cell morphology/orientation. Nanofiber organization
      is controlled with a new fabrication apparatus that enables the gradual decrease
      of fiber organization in a scaffold. Changing the alignment of fibers is achieved
      through decreasing deposition time of random electrospun fibers on a uniaxially
      aligned fiber mat. By covering the collector with a moving barrier/mask, along
      the same axis as fiber deposition, the organizational structure is easily
      controlled. For tissue engineering purposes, adipose-derived stem cells can be
      seeded to these scaffolds. Stem cells undergo morphological changes as a result
      of their position on the varied organizational structure, and can potentially
      differentiate into different cell types depending on their locations.
      Additionally, the graded organization of fibers enhances the biomimicry of
      nanofiber scaffolds so they more closely resemble the natural orientations of
      collagen nanofibers at tendon-to-bone insertion site compared to traditional
      scaffolds. Through nanoencapsulation, the gradated fibers also afford the
      possibility to construct chemical gradients in fiber scaffolds, and thereby
      further strengthen their potential applications in fast screening of cell
      materials interaction and interfacial tissue regeneration. This technique enables
      the production of continuous gradient scaffolds, but it also can potentially
      produce fibers in discrete steps by controlling the movement of the moving
      barrier/mask in a discrete fashion. 

PMID- 25938561
TI  - Interhemispheric Functional and Structural Disconnection in Alzheimer's Disease:
      A Combined Resting-State fMRI and DTI Study.
AB  - Neuroimaging studies have demonstrated that patients with Alzheimer's disease
      presented disconnection syndrome. However, little is known about the alterations
      of interhemispheric functional interactions and underlying structural
      connectivity in the AD patients. In this study, we combined resting-state
      functional MRI and diffusion tensor imaging (DTI) to investigate interhemispheric
      functional and structural connectivity in 16 AD, 16 mild cognitive impairment
      (MCI), as well as 16 cognitive normal healthy subjects (CN). The pattern of the
      resting state interhemispheric functional connectivity was measured with a voxel
      mirrored homotopic connectivity (VMHC) method. Decreased VMHC was observed in AD
      and MCI subjects in anterior brain regions including the prefrontal cortices and
      subcortical regions with a pattern of AD<MCI<CN. Increased VMHC was observed in
      MCI subjects in posterior brain regions with patterns of AD/CN < MCI
      (sensorimotor cortex) and AD < CN/MCI (occipital gyrus). DTI analysis showed the
      most significant difference among the three cohorts was the fractional anisotropy
      in the genu of corpus callosum, which was positively associated with the VMHC of
      prefrontal and subcortical regions. Across all the three cohorts, the diffusion
      parameters in the genu of corpus callosum and VMHC in the above brain regions had
      significant correlation with the cognitive performance. These results demonstrate
      that there are specific patterns of interhemispheric functional connectivity
      changes in the AD and MCI, which can be significantly correlated with the
      integrity changes in the midline white matter structures. These results suggest
      that VMHC can be used as a biomarker for the degeneration of the interhemispheric
      connectivity in AD. 

PMID- 25938563
TI  - Posterior fossa arteriovenous malformations: Significance of higher incidence of
      bleeding and hydrocephalus.
AB  - OBJECTIVE: Hydrocephalus associated with different types of intracranial
      arteriovenous malformations (AVMs) has been scarcely studied. In the present
      report we investigate this association with posterior fossa AVMs (pfAVMs). We
      hypothesized that there is an increased risk of hydrocephalus and required
      permanent cerebrospinal fluid (CSF) shunt in patients with pfAVMs that may be
      linked to the increased risk of bleeding of these lesions. We also review the
      factors associated with this increased risk of hemorrhagic presentation and we
      assess how it affects management strategies and functional outcomes in these
      patients. METHODS: Out of a prospective registry of 374 patients with brain AVMs
      diagnosed in our center from 1993 to 2013, 60 (16%) had a pfAVM. We described
      these patients' demographics, their AVM characteristics, clinical presentation,
      and hydrocephalus incidence and compared the results with those of the
      supratentorial AVM (spAVM) patients recorded during the same period. RESULTS: Out
      of the 60 patients with pfAVMs, 10 (16.7%) presented AVMs located in the
      brainstem. Hemorrhagic presentation (49/60; 82%) was significantly higher in
      pfAVMs than in spAVMs (122/314; 38.8%; p<0.05). Hydrocephalus was a common
      complication in pfAVM patients who had a statistically significant higher need
      for both temporary external ventricular drain (EVD) (6.7 vs. 20%; p<0.05) and
      permanent CSF shunts (3.5 vs. 20%; p<0.05). The initial mortality was high
      (12/60; 20.3%) and half of these patients died before any treatment option could
      be offered. However, out of those who survived, 70% (42/60) had already shown
      good clinical outcome at the 6-month follow-up. CONCLUSIONS: Hemorrhagic
      presentation and hydrocephalus have a higher incidence in pfAVM patients, which
      initially results in more neurological deficits and an elevated mortality even
      before receiving any treatment. However, a large number of survivors present good
      functional outcomes at early follow-up, justifying an aggressive management
      strategy with microsurgery as the first treatment option in most cases, and
      radiosurgery as an alternative, especially in brainstem AVMs.

PMID- 25938564
TI  - MRI diagnosis of dural sinus - Cortical venous thrombosis: Immediate post
      contrast 3D GRE T1-weighted imaging versus unenhanced MR venography and
      conventional MR sequences.
AB  - OBJECTIVE: Primary aim is to compare the diagnostic value of contrast-enhanced 3D
      GRE T1-weighted sequences with unenhanced MR venography and conventional magnetic
      resonance imaging (MRI), in detection of dural venous sinus (DVS) and cortical
      venous thrombosis; secondary aim is to determine the relationship between DVS
      thrombosis/site and gender, age, infarction or hemorrhage. METHODS: We
      retrospectively reviewed conventional MR images, unenhanced MR venography and
      immediate post-contrast 3D GRE T1-weighted MR images in 30 patients (17 male and
      13 female, 21-70 years old, mean age 40.1) with clinically suspected DVS
      thrombosis. MR examinations had been performed with 1.5T or 3T MR Scanners. DVSs
      were evaluated in 10 sub-segments, including cortical veins. Each set of MR
      images were examined separately, blinded to the final diagnosis. Associated
      findings were also noted and sensitivity, specificity and accuracy of each MRI
      technique were calculated. RESULTS: Final diagnosis of cortical venous and/or
      dural sinus thrombosis was established in 24 (80%) of 30 cases and 67 (22.3%) out
      of 300 segments. For detection of the thrombotic segment, sensitivity,
      specificity, and accuracy were 83.6%, 95.3%, and 92.7% by conventional MR
      sequences, 89.6%, 91.8%, and 91.3% by unenhanced MR venography, and 92.5%, 100%,
      and 98.3% by contrast-enhanced 3D GRE T1-weighted sequence, respectively.
      Infarction and hemorrhage were more frequent in cases with cortical venous
      thrombosis, while gender and age had no significant relation with DVS thrombosis
      or its site. Conventional MR sequences and unenhanced MR venography were helpful
      due to additional information they provided in some cases with isolated cortical
      venous thrombosis, with hyperintense thrombus material and with associated
      hemorrhage or infarction. CONCLUSION: Contrast-enhanced 3D GRE T1-weighted MRI is
      the most accurate imaging method for the detection of DVS and/or cortical venous
      thrombosis. Infarction and hemorrhage were more frequent in cases with cortical
      venous thrombosis.

PMID- 25938565
TI  - Quantitative Analysis of the Enhanced Permeation and Retention (EPR) Effect.
AB  - Tumor vasculature is characterized by a variety of abnormalities including
      irregular architecture, poor lymphatic drainage, and the upregulation of factors
      that increase the paracellular permeability. The increased permeability is
      important in mediating the uptake of an intravenously administered drug in a
      solid tumor and is known as the enhanced permeation and retention (EPR) effect.
      Studies in animal models have demonstrated a cut-off size of 500 nm - 1 um for
      molecules or nanoparticles to extravasate into a tumor, however, surprisingly
      little is known about the kinetics of the EPR effect. Here we present a
      pharmacokinetic model to quantitatively assess the influence of the EPR effect on
      the uptake of a drug into a solid tumor. We use pharmacokinetic data for Doxil
      and doxorubicin from human clinical trials to illustrate how the EPR effect
      influences tumor uptake. This model provides a quantitative framework to guide
      preclinical trials of new chemotherapies and ultimately to develop design rules
      that can increase targeting efficiency and decrease unwanted side effects in
      normal tissue. 

PMID- 25938566
TI  - The Reg3alpha (HIP/PAP) Lectin Suppresses Extracellular Oxidative Stress in a
      Murine Model of Acute Liver Failure.
AB  - BACKGROUND AND AIMS: Acute liver failure (ALF) is a rapidly progressive
      heterogeneous illness with high mortality rate and no widely accessible cure. A
      promising drug candidate according to previous preclinical studies is the
      Reg3alpha (or HIP/PAP) lectin, which alleviates ALF through its free-radical
      scavenging activity. Here we study the therapeutic targets of Reg3alpha in order
      to gain information on the nature of the oxidative stress associated with ALF.
      METHODS: Primary hepatocytes stressed with the reactive oxygen species (ROS)
      inducers TNFalpha and H2O2 were incubated with a recombinant Reg3alpha protein.
      ALF was induced in C57BL/6J mice by an anti-CD95 antibody. Livers and primary
      hepatocytes were harvested for deoxycholate separation of cellular and
      extracellular fractions, immunostaining, immunoprecipitation and malondialdehyde
      assays. Fibrin deposition was studied by immunofluorescence in frozen liver
      explants from patients with ALF. RESULTS: Fibrin deposition occurs during
      experimental and clinical acute liver injuries. Reg3alpha bound the resulting
      transient fibrin network, accumulated in the inflammatory extracellular matrix
      (ECM), greatly reduced extracellular ROS levels, and improved cell viability.
      Hepatocyte treatment with ligands of death receptors, e.g. TNFalpha and Fas,
      resulted in a twofold increase of malondialdehyde (MDA) level in the deoxycholate
      insoluble fractions. Reg3alpha treatment maintained MDA at a level similar to
      control cells and thereby increased hepatocyte survival by 35%. No antioxidant
      effect of Reg3alpha was noted in the deoxycholate-soluble fractions. Preventing
      fibrin network formation with heparin suppressed the prosurvival effect of
      Reg3alpha. CONCLUSIONS: Reg3alpha is an ECM-targeted ROS scavenger that binds the
      fibrin scaffold resulting from hepatocyte death during ALF. ECM alteration is an
      important pathogenic factor of ALF and a relevant target for pharmacotherapy.

PMID- 25938567
TI  - The CAF-1 and Hir Histone Chaperones Associate with Sites of Meiotic Double
      Strand Breaks in Budding Yeast.
AB  - In the meiotic prophase, programmed DNA double-strand breaks (DSB) are introduced
      along chromosomes to promote homolog pairing and recombination. Although meiotic
      DSBs usually occur in nucleosome-depleted, accessible regions of chromatin, their
      repair by homologous recombination takes place in a nucleosomal environment.
      Nucleosomes may represent an obstacle for the recombination machinery and their
      timely eviction and reincorporation into chromatin may influence the outcome of
      recombination, for instance by stabilizing recombination intermediates. Here we
      show in budding yeast that nucleosomes flanking a meiotic DSB are transiently
      lost during recombination, and that specific histone H3 chaperones, CAF-1 and
      Hir, are mobilized at meiotic DSBs. However, the absence of these chaperones has
      no effect on meiotic recombination, suggesting that timely histone
      reincorporation following their eviction has no influence on the recombination
      outcome, or that redundant pathways are activated. This study is the first
      example of the involvement of histone H3 chaperones at naturally occurring,
      developmentally programmed DNA double-strand breaks. 

PMID- 25938568
TI  - Genetic diversity in oxytocin ligands and receptors in New World monkeys.
AB  - Oxytocin (OXT) is an important neurohypophyseal hormone that influences wide
      spectrum of reproductive and social processes. Eutherian mammals possess a highly
      conserved sequence of OXT (Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly). However, in this
      study, we sequenced the coding region for OXT in 22 species covering all New
      World monkeys (NWM) genera and clades, and characterize five OXT variants,
      including consensus mammalian Leu(8)-OXT, major variant Pro(8)-OXT, and three
      previously unreported variants: Ala(8)-OXT, Thr(8)-OXT, and Phe(2)-OXT. Pro(8)
      OXT shows clear structural and physicochemical differences from Leu(8)-OXT. We
      report multiple predicted amino acid substitutions in the G protein-coupled OXT
      receptor (OXTR), especially in the critical N-terminus, which is crucial for OXT
      recognition and binding. Genera with same Pro(8)-OXT tend to cluster together on
      a phylogenetic tree based on OXTR sequence, and we demonstrate significant
      coevolution between OXT and OXTR. NWM species are characterized by high incidence
      of social monogamy, and we document an association between OXTR phylogeny and
      social monogamy. Our results demonstrate remarkable genetic diversity in the NWM
      OXT/OXTR system, which can provide a foundation for molecular, pharmacological,
      and behavioral studies of the role of OXT signaling in regulating complex social
      phenotypes.

PMID- 25938569
TI  - Voltage-controlled quantum light from an atomically thin semiconductor.
AB  - Although semiconductor defects can often be detrimental to device performance,
      they are also responsible for the breadth of functionality exhibited by modern
      optoelectronic devices. Artificially engineered defects (so-called quantum dots)
      or naturally occurring defects in solids are currently being investigated for
      applications ranging from quantum information science and optoelectronics to high
      resolution metrology. In parallel, the quantum confinement exhibited by
      atomically thin materials (semi-metals, semiconductors and insulators) has
      ushered in an era of flatland optoelectronics whose full potential is still being
      articulated. In this Letter we demonstrate the possibility of leveraging the
      atomically thin semiconductor tungsten diselenide (WSe2) as a host for quantum
      dot-like defects. We report that this previously unexplored solid-state quantum
      emitter in WSe2 generates single photons with emission properties that can be
      controlled via the application of external d.c. electric and magnetic fields.
      These new optically active quantum dots exhibit excited-state lifetimes on the
      order of 1 ns and remarkably large excitonic g-factors of 10. It is anticipated
      that WSe2 quantum dots will provide a novel platform for integrated solid-state
      quantum photonics and quantum information processing, as well as a rich condensed
      matter physics playground with which to explore the coupling of quantum dots and
      atomically thin semiconductors. 

PMID- 25938570
TI  - Optically active quantum dots in monolayer WSe2.
AB  - Semiconductor quantum dots have emerged as promising candidates for the
      implementation of quantum information processing, because they allow for a
      quantum interface between stationary spin qubits and propagating single photons.
      In the meantime, transition-metal dichalcogenide monolayers have moved to the
      forefront of solid-state research due to their unique band structure featuring a
      large bandgap with degenerate valleys and non-zero Berry curvature. Here, we
      report the observation of zero-dimensional anharmonic quantum emitters, which we
      refer to as quantum dots, in monolayer tungsten diselenide, with an energy that
      is 20-100 meV lower than that of two-dimensional excitons. Photon antibunching in
      second-order photon correlations unequivocally demonstrates the zero-dimensional
      anharmonic nature of these quantum emitters. The strong anisotropic magnetic
      response of the spatially localized emission peaks strongly indicates that
      radiative recombination stems from localized excitons that inherit their
      electronic properties from the host transition-metal dichalcogenide. The large ~1
      meV zero-field splitting shows that the quantum dots have singlet ground states
      and an anisotropic confinement that is most probably induced by impurities or
      defects. The possibility of achieving electrical control in van der Waals
      heterostructures and to exploit the spin-valley degree of freedom renders
      transition-metal-dichalcogenide quantum dots interesting for quantum information
      processing. 

PMID- 25938571
TI  - Single quantum emitters in monolayer semiconductors.
AB  - Single quantum emitters (SQEs) are at the heart of quantum optics and photonic
      quantum-information technologies. To date, all the demonstrated solid-state
      single-photon sources are confined to one-dimensional (1D; ref. 3) or 3D
      materials. Here, we report a new class of SQEs based on excitons that are
      spatially localized by defects in 2D tungsten-diselenide (WSe2) monolayers. The
      optical emission from these SQEs shows narrow linewidths of ~130 MUeV, about two
      orders of magnitude smaller than those of delocalized valley excitons. Second
      order correlation measurements revealed a strong photon antibunching, which
      unambiguously established the single-photon nature of the emission. The SQE
      emission shows two non-degenerate transitions, which are cross-linearly
      polarized. We assign this fine structure to two excitonic eigenmodes whose
      degeneracy is lifted by a large ~0.71 meV coupling, probably because of the
      electron-hole exchange interaction in the presence of anisotropy. Magneto-optical
      measurements also reveal an exciton g factor of ~8.7, several times larger than
      those of delocalized valley excitons. In addition to their fundamental
      importance, establishing new SQEs in 2D quantum materials could give rise to
      practical advantages in quantum-information processing, such as an efficient
      photon extraction and a high integratability and scalability. 

PMID- 25938572
TI  - Metal dichalcogenides: Two dimensions and one photon.

PMID- 25938573
TI  - Single photon emitters in exfoliated WSe2 structures.
AB  - Crystal structure imperfections in solids often act as efficient carrier trapping
      centres, which, when suitably isolated, act as sources of single photon emission.
      The best known examples of such attractive imperfections are well-width or
      composition fluctuations in semiconductor heterostructures (resulting in the
      formation of quantum dots) and coloured centres in wide-bandgap materials such as
      diamond. In the recently investigated thin films of layered compounds, the
      crystal imperfections may logically be expected to appear at the edges of
      commonly investigated few-layer flakes of these materials exfoliated on alien
      substrates. Here, we report comprehensive optical micro-spectroscopy studies of
      thin layers of tungsten diselenide (WSe2), a representative semiconducting
      dichalcogenide with a bandgap in the visible spectral range. At the edges of WSe2
      flakes (transferred onto Si/SiO2 substrates) we discover centres that, at low
      temperatures, give rise to sharp emission lines (100 MUeV linewidth). These
      narrow emission lines reveal the effect of photon antibunching, the unambiguous
      attribute of single photon emitters. The optical response of these emitters is
      inherently linked to the two-dimensional properties of the WSe2 monolayer, as
      they both give rise to luminescence in the same energy range, have nearly
      identical excitation spectra and have very similar, characteristically large
      Zeeman effects. With advances in the structural control of edge imperfections,
      thin films of WSe2 may provide added functionalities that are relevant for the
      domain of quantum optoelectronics. 

PMID- 25938574
TI  - Pollutant emissions from improved coal- and wood-fuelled cookstoves in rural
      households.
AB  - Residential solid fuel combustion is a major source of many pollutants, resulting
      in significant impacts on air quality and human health. Improved stoves,
      especially some modern gasifier biomass models, are being deployed to alleviate
      household and ambient air pollution. Pollutant emissions from coal burning in
      improved metal stoves (n = 11) and wood combustion in modern gasifier stoves (n =
      8) were measured in field in Hubei, China. The emissions of CO, TSP, OC, EC, and
      PAHs from coal burning in the improved iron stoves were generally lower than
      previously reported results for coal in traditional stoves. For pollutants from
      wood combustion in the gasifier stoves, the emissions were less than literature
      reported values for wood burned in traditional stoves, comparable to those in
      improved stoves, but appeared to be higher than those for pellets in gasifier
      stoves in laboratory tests. The limitations of scarce data and large variances
      result in statistical insignificance. Daily emissions of targeted pollutants per
      household were found to be higher for wood burners, compared with households
      relying on coal. The gasifier stove had relatively high thermal efficiencies, but
      emissions of most air pollutants per delivered energy were not significantly
      different from those from the coal burning in improved iron stoves. Moreover,
      higher emissions of OC, EC, and PAHs were observed, indicating that caution and
      additional testing will be needed while designing future clean cookstove
      intervention programs. 

PMID- 25938575
TI  - Comparison of the Relationship between Cerebral White Matter and Grey Matter in
      Normal Dogs and Dogs with Lateral Ventricular Enlargement.
AB  - Large cerebral ventricles are a frequent finding in brains of dogs with
      brachycephalic skull conformation, in comparison with mesaticephalic dogs. It
      remains unclear whether oversized ventricles represent a normal variant or a
      pathological condition in brachycephalic dogs. There is a distinct relationship
      between white matter and grey matter in the cerebrum of all eutherian mammals.
      The aim of this study was to determine if this physiological proportion between
      white matter and grey matter of the forebrain still exists in brachycephalic dogs
      with oversized ventricles. The relative cerebral grey matter, white matter and
      cerebrospinal fluid volume in dogs were determined based on magnetic-resonance
      imaging datasets using graphical software. In an analysis of covariance (ANCOVA)
      using body mass as the covariate, the adjusted means of the brain tissue volumes
      of two groups of dogs were compared. Group 1 included 37 mesaticephalic dogs of
      different sizes with no apparent changes in brain morphology, and subjectively
      normal ventricle size. Group 2 included 35 brachycephalic dogs in which
      subjectively enlarged cerebral ventricles were noted as an incidental finding in
      their magnetic-resonance-imaging examination. Whereas no significant different
      adjusted means of the grey matter could be determined, the group of
      brachycephalic dogs had significantly larger adjusted means of lateral cerebral
      ventricles and significantly less adjusted means of relative white matter volume.
      This indicates that brachycephalic dogs with subjective ventriculomegaly have
      less white matter, as expected based on their body weight and cerebral volume.
      Our study suggests that ventriculomegaly in brachycephalic dogs is not a normal
      variant of ventricular volume. Based on the changes in the relative proportion of
      WM and CSF volume, and the unchanged GM proportions in dogs with
      ventriculomegaly, we rather suggest that distension of the lateral ventricles
      might be the underlying cause of pressure related periventricular loss of white
      matter tissue, as occurs in internal hydrocephalus. 

PMID- 25938576
TI  - An optimized enrichment technique for the isolation of Arthrobacter bacteriophage
      species from soil sample isolates.
AB  - Bacteriophage isolation from environmental samples has been performed for decades
      using principles set forth by pioneers in microbiology. The isolation of phages
      infecting Arthrobacter hosts has been limited, perhaps due to the low success
      rate of many previous isolation techniques, resulting in an underrepresented
      group of Arthrobacter phages available for study. The enrichment technique
      described here, unlike many others, uses a filtered extract free of contaminating
      bacteria as the base for indicator bacteria growth, Arthrobacter sp. KY3901,
      specifically. By first removing soil bacteria the target phages are not hindered
      by competition with native soil bacteria present in initial soil samples. This
      enrichment method has resulted in dozens of unique phages from several different
      soil types and even produced different types of phages from the same enriched
      soil sample isolate. The use of this procedure can be expanded to most nutrient
      rich aerobic media for the isolation of phages in a vast diversity of interesting
      host bacteria.

PMID- 25938577
TI  - Antibody structural integrity of site-specific antibody-drug conjugates
      investigated by hydrogen/deuterium exchange mass spectrometry.
AB  - We present the results of a hydrogen/deuterium exchange mass spectrometric (HDX
      MS) investigation of an antibody-drug conjugate (ADC) comprised of drug-linkers
      conjugated to cysteine residues that have been engineered into heavy chain (HC)
      fragment crystallizable (Fc) domain at position 239. A side-by-side comparison of
      the HC Ser239 wild type (wt) monoclonal antibody (mAb) and the engineered Cys239
      mAb indicates that site directed mutagenesis of Ser239 to cysteine has no impact
      on the HDX kinetics of the mAb. According to the crystal structure of a
      homologous immunoglobulin G1 (IgG1) antibody (PDB: 1HZH ), the backbone amide of
      Ser239 is hydrogen-bonded to Val264 backbone amide in the wt-mAb studied here.
      Replacing Ser239 with a Cys residue does not alter the exchange kinetics of the
      backbone amide of Val264 suggesting that either Ser or Cys at position 239 has
      similar amide-hydrogen bonding with Val264. However, a small segment in CH2
      domain of the ADC ((264)VDVS) was found to have a slightly increased HDX rate
      compared to the wt- and C239-mAb constructs. The slightly increased HDX rate of
      the segment (264)VDVS in ADCs indicates that the further modification of Cys239
      with drug-linkers only attenuates the local backbone amide hydrogen-bonding
      network between Cys239 and Val264. All other regions which are proximal to the
      site of drug conjugation are unaffected. The results demonstrate that the site
      specific drug conjugation at the engineered Cys residue at the position 239 of HC
      does not impact the structural integrity of antibodies. The results also
      highlight the utility of applying HDX-MS to ADCs to gain a molecular level
      insight into the impact of site-specific conjugation technologies on the higher
      order structure (HOS) of mAbs. The methodology can be applied generally to site
      specific ADC modalities to understand the individual contributions of site
      mutagenesis and drug-linker conjugation on the HOS of therapeutic candidate ADCs.

PMID- 25938578
TI  - Thiamethoxam Resistance in the House Fly, Musca domestica L.: Current Status,
      Resistance Selection, Cross-Resistance Potential and Possible Biochemical
      Mechanisms.
AB  - The house fly, Musca domestica L., is an important ectoparasite with the ability
      to develop resistance to insecticides used for their control. Thiamethoxam, a
      neonicotinoid, is a relatively new insecticide and effectively used against house
      flies with a few reports of resistance around the globe. To understand the status
      of resistance to thiamethoxam, eight adult house fly strains were evaluated under
      laboratory conditions. In addition, to assess the risks of resistance
      development, cross-resistance potential and possible biochemical mechanisms, a
      field strain of house flies was selected with thiamethoxam in the laboratory. The
      results revealed that the field strains showed varying level of resistance to
      thiamethoxam with resistance ratios (RR) at LC50 ranged from 7.66-20.13 folds.
      Continuous selection of the field strain (Thia-SEL) for five generations
      increased the RR from initial 7.66 fold to 33.59 fold. However, resistance
      declined significantly when the Thia-SEL strain reared for the next five
      generations without exposure to thiamethoxam. Compared to the laboratory
      susceptible reference strain (Lab-susceptible), the Thia-SEL strain showed cross
      resistance to imidacloprid. Synergism tests revealed that S,S,S
      tributylphosphorotrithioate (DEF) and piperonyl butoxide (PBO) produced synergism
      of thiamethoxam effects in the Thia-SEL strain (2.94 and 5.00 fold,
      respectively). In addition, biochemical analyses revealed that the activities of
      carboxylesterase (CarE) and mixed function oxidase (MFO) in the Thia-SEL strain
      were significantly higher than the Lab-susceptible strain. It seems that
      metabolic detoxification by CarE and MFO was a major mechanism for thiamethoxam
      resistance in the Thia-SEL strain of house flies. The results could be helpful in
      the future to develop an improved control strategy against house flies. 

PMID- 25938579
TI  - Ultrafast 2D-IR and simulation investigations of preferential solvation and
      cosolvent exchange dynamics.
AB  - Using a derivative of the vitamin biotin labeled with a transition-metal carbonyl
      vibrational probe in a series of aqueous N,N-dimethylformamide (DMF) solutions,
      we observe a striking slowdown in spectral diffusion dynamics with decreased DMF
      concentration. Equilibrium solvation dynamics, measured with the rapidly acquired
      spectral diffusion (RASD) technique, a variant of heterodyne-detected photon-echo
      peak shift experiments, range from 1 ps in neat DMF to ~3 ps in 0.07 mole
      fraction DMF/water solution. Molecular dynamics simulations of the biotin-metal
      carbonyl solute in explicit aqueous DMF solutions show marked preferential
      solvation by DMF, which becomes more pronounced at lower DMF concentrations. The
      simulations and the experimental data are consistent with an interpretation where
      the slowdown in spectral diffusion is due to solvent exchange involving distinct
      cosolvent species. A simple two-component model reproduces the observed spectral
      dynamics as well as the DMF concentration dependence, enabling the extraction of
      the solvent exchange time scale of 8 ps. This time scale corresponds to the
      diffusive motion of a few A, consistent with a solvent-exchange mechanism. Unlike
      most previous studies of solvation dynamics in binary mixtures of polar solvents,
      our work highlights the ability of vibrational probes to sense solvent exchange
      as a new, slow component in the spectral diffusion dynamics. 

PMID- 25938580
TI  - Effects of plant diversity, functional group composition, and fertilization on
      soil microbial properties in experimental grassland.
AB  - BACKGROUND: Loss of biodiversity and increased nutrient inputs are two of the
      most crucial anthropogenic factors driving ecosystem change. Although both
      received considerable attention in previous studies, information on their
      interactive effects on ecosystem functioning is scarce. In particular, little is
      known on how soil biota and their functions are affected by combined changes in
      plant diversity and fertilization. METHODOLOGY/PRINCIPAL FINDINGS: We
      investigated the effects of plant diversity, functional community composition,
      and fertilization on the biomass and respiration of soil microbial communities in
      a long-term biodiversity experiment in semi-natural grassland (Jena Experiment).
      Plant species richness enhanced microbial basal respiration and microbial
      biomass, but did not significantly affect microbial specific respiration. In
      contrast, the presence of legumes and fertilization significantly decreased
      microbial specific respiration, without altering microbial biomass. The effect of
      legumes was superimposed by fertilization as indicated by a significant
      interaction between the presence of legumes and fertilization. Further, changes
      in microbial stoichiometry (C-to-N ratio) and specific respiration suggest the
      presence of legumes to reduce N limitation of soil microorganisms and to modify
      microbial C use efficiency. CONCLUSIONS/SIGNIFICANCE: Our study highlights the
      role of plant species and functional group diversity as well as interactions
      between plant community composition and fertilizer application for soil microbial
      functions. Our results suggest soil microbial stoichiometry to be a powerful
      indicator of microbial functioning under N limited conditions. Although our
      results support the notion that plant diversity and fertilizer application
      independently affect microbial functioning, legume effects on microbial N
      limitation were superimposed by fertilization, indicating significant
      interactions between the functional composition of plant communities and nutrient
      inputs for soil processes.

PMID- 25938581
TI  - Chemoselective Reductive Amination of Carbonyl Compounds for the Synthesis of
      Tertiary Amines Using SnCl2.2H2O/PMHS/MeOH.
AB  - Stannous chloride catalyzed chemoselective reductive amination of a variety of
      carbonyl compounds with aromatic amines has been developed for the synthesis of a
      diverse range of tertiary amines using inexpensive polymethylhydrosiloxane as
      reducing agent in methanol. The present method is also applicable for the
      synthesis of secondary amines including heterocyclic ones. 

PMID- 25938582
TI  - Ecological relationships of meso-scale distribution in 25 neotropical vertebrate
      species.
AB  - Vertebrates are a vital ecological component of Amazon forest biodiversity.
      Although vertebrates are a functionally important part of various ecosystem
      services they continue to be threatened by anthropogenic impacts throughout the
      Amazon. Here we use a standardized, regularly spaced arrangement of camera traps
      within 25km2 to provide a baseline assessment of vertebrate species diversity in
      a sustainable use protected area in the eastern Brazilian Amazon. We examined
      seasonal differences in the per species encounter rates (number of photos per
      camera trap and number of cameras with photos). Generalized linear models (GLMs)
      were then used to examine the influence of five variables (altitude, canopy
      cover, basal area, distance to nearest river and distance to nearest large river)
      on the number of photos per species and on functional groups. GLMs were also used
      to examine the relationships between large predators [Jaguar (Panthera onca) and
      Puma (Puma concolor)] and their prey. A total of 649 independent photos of 25
      species were obtained from 1,800 camera trap days (900 each during wet and dry
      seasons). Only ungulates and rodents showed significant seasonal differences in
      the number of photos per camera. The number of photos differed between seasons
      for only three species (Mazama americana, Dasyprocta leporina and Myoprocta
      acouchy) all of which were photographed more (3 to 10 fold increase) during the
      wet season. Mazama americana was the only species where a significant difference
      was found in occupancy, with more photos in more cameras during the wet season.
      For most groups and species variation in the number of photos per camera was only
      explained weakly by the GLMs (deviance explained ranging from 10.3 to 54.4%).
      Terrestrial birds (Crax alector, Psophia crepitans and Tinamus major) and rodents
      (Cuniculus paca, Dasyprocta leporina and M. acouchy) were the notable exceptions,
      with our GLMs significantly explaining variation in the distribution of all
      species (deviance explained ranging from 21.0 to 54.5%). The group and species
      GLMs showed some novel ecological information from this relatively pristine area.
      We found no association between large cats and their potential prey. We also
      found that rodent and bird species were more often recorded closer to streams. As
      hunters gain access via rivers this finding suggests that there is currently
      little anthropogenic impact on the species. Our findings provide a standardized
      baseline for comparison with other sites and with which planned management and
      extractive activities can be evaluated. 

PMID- 25938583
TI  - Human Dupuytren's Ex Vivo Culture for the Study of Myofibroblasts and
      Extracellular Matrix Interactions.
AB  - Organ fibrosis or "scarring" is known to account for a high death toll due to the
      extensive amount of disorders and organs affected (from cirrhosis to
      cardiovascular diseases). There is no effective treatment and the in vitro tools
      available do not mimic the in vivo situation rendering the progress of the out of
      control wound healing process still enigmatic. To date, 2D and 3D cultures of
      fibroblasts derived from DD patients are the main experimental models available.
      Primary cell cultures have many limitations; the fibroblasts derived from DD are
      altered by the culture conditions, lack cellular context and interactions, which
      are crucial for the development of fibrosis and weakly represent the derived
      tissue. Real-time PCR analysis of fibroblasts derived from control and DD samples
      show that little difference is detectable. 3D cultures of fibroblasts include
      addition of extracellular matrix that alters the native conditions of these
      cells. As a way to characterize the fibrotic, proliferative properties of these
      resection specimens we have developed a 3D culture system, using intact human
      resections of the nodule part of the cord. The system is based on transwell
      plates with an attached nitrocellulose membrane that allows contact of the tissue
      with the medium but not with the plastic, thus, preventing the alteration of the
      tissue. No collagen gel or other extracellular matrix protein substrate is
      required. The tissue resection specimens maintain their viability and
      proliferative properties for 7 days. This is the first "organ" culture system
      that allows human resection specimens from DD patients to be grown ex vivo and
      functionally tested, recapitulating the in vivo situation. 

PMID- 25938584
TI  - Incidence and Risk Factors of Childhood Pneumonia-Like Episodes in Biliran
      Island, Philippines--A Community-Based Study.
AB  - Pneumonia is a leading cause of deaths in infants and young children in
      developing countries, including the Philippines. However, data at the community
      level remains limited. Our study aimed to estimate incidence and mortality rates
      and to evaluate risk factors and health-seeking behavior for childhood pneumonia.
      A household level interview survey was conducted in Biliran Island, the
      Philippines. Caregivers were interviewed using a semi-structured questionnaire to
      check if children had symptoms suggesting pneumonia-like episodes from June 2011
      to May 2012. Of 3,327 households visited in total, 3,302 (99.2%) agreed to
      participate, and 5,249 children less than 5 years of age were included in the
      study. Incidence rates of pneumonia-like episodes, severe pneumonia-like
      episodes, and pneumonia-associated mortality were 105, 61, and 0.9 per 1,000
      person-years, respectively. History of asthma [hazard ratio (HR): 5.85, 95%
      confidence interval (CI): 4.83-7.08], low socioeconomic status (SES) (HR: 1.11,
      95% CI: 1.02-1.20), and long travel time to the healthcare facility estimated by
      cost distance analysis (HR: 1.32, 95% CI: 1.09-1.61) were significantly
      associated with the occurrence of pneumonia-like episodes by the Cox proportional
      hazards model. For severe pneumonia-like episodes, a history of asthma (HR: 8.39,
      95% CI: 6.54-10.77) and low SES (HR: 1.30, 95% CI: 1.17-1.45) were significant
      risk factors. Children who had a long travel time to the hospital were less
      likely to seek hospital care (Odds ratio: 0.32, 95% CI: 0.19-0.54) when they
      experienced severe pneumonia-like episodes. Incidence of pediatric pneumonia-like
      episodes was associated with a history of asthma, SES, and the travel time to
      healthcare facilities. Travel time was also identified as a strong indicator for
      health-seeking behavior. Improved access to healthcare facilities is important
      for early and effective management. Further studies are warranted to understand
      the causal relationship between asthma and pneumonia. 

PMID- 25938585
TI  - Nicotinamide impairs entry into and exit from meiosis I in mouse oocytes.
AB  - Following exit from meiosis I, mammalian oocytes immediately enter meiosis II
      without an intervening interphase, accompanied by rapid reassembly of a bipolar
      spindle that maintains condensed chromosomes in a metaphase configuration
      (metaphase II arrest). Here we study the effect of nicotinamide (NAM), a non
      competitive pan-sirtuin inhibitor, during meiotic maturation in mouse oocytes.
      Sirtuins are a family of seven NAD+-dependent deacetylases (Sirt1-7), which are
      involved in multiple cellular processes and are emerging as important regulators
      in oocytes and embryos. We found that NAM significantly delayed entry into
      meiosis I associated with delayed accumulation of the Cdk1 co-activator, cyclin
      B1. GVBD was also inhibited by the Sirt2-specific inhibitor, AGK2, and in a very
      similar pattern to NAM, supporting the notion that as in somatic cells, NAM
      inhibits sirtuins in oocytes. NAM did not affect subsequent spindle assembly,
      chromosome alignment or the timing of first polar body extrusion (PBE).
      Unexpectedly, however, in the majority of oocytes with a polar body, chromatin
      was decondensed and a nuclear structure was present. An identical phenotype was
      observed when flavopiridol was used to induce Cdk1 inactivation during late
      meiosis I prior to PBE, but not if Cdk1 was inactivated after PBE when metaphase
      II arrest was already established, altogether indicating that NAM impaired
      establishment rather than maintenance of metaphase II arrest. During meiosis I
      exit in NAM-treated medium, we found that cyclin B1 levels were lower and
      inhibitory Cdk1 phosphorylation was increased compared with controls. Although
      activation of the anaphase-promoting complex-Cdc20 (APC-Cdc20) occurred on-time
      in NAM-treated oocytes, Cdc20 levels were higher in very late meiosis I, pointing
      to exaggerated APC-Cdc20-mediated proteolysis as a reason for lower cyclin B1
      levels. Collectively, therefore, our data indicate that by disrupting Cdk1
      regulation, NAM impairs entry into meiosis I and the establishment of metaphase
      II arrest. 

PMID- 25938586
TI  - Maternal Exposure of a Beetle to Pathogens Protects Offspring against Fungal
      Disease.
AB  - Maternal exposure to an immune challenge can convey enhanced immunity to
      invertebrate offspring in the next generation. We investigated whether maternal
      exposure of the Asian longhorned beetle, Anoplophora glabripennis, to two species
      of the fungus Metarhizium or the bacterium Serratia marcescens elicited
      transgenerational immune priming (TGIP). We tested specificity of this protection
      and whether occurrence of TGIP was dependent on maternal exposure to living
      versus dead pathogens. Our results show that TGIP occurred and protected
      offspring against Metarhizium brunneum. Maternal exposure to S. marcescens
      provided non-specific protection to offspring against a fungal pathogen, but TGIP
      in response to Metarhizium only occurred when offspring were exposed to the same
      fungal species that was used to prime mothers. Moreover, TGIP in response to M.
      brunneum occurred only after maternal exposure to living rather than dead fungus.
      Our findings suggest that occurrence of TGIP could be both specific and dependent
      on whether the pathogen was alive. 

PMID- 25938587
TI  - Consensus comparative analysis of human embryonic stem cell-derived
      cardiomyocytes.
AB  - Global transcriptional analyses have been performed with human embryonic stem
      cells (hESC) derived cardiomyocytes (CMs) to identify molecules and pathways
      important for human CM differentiation, but variations in culture and profiling
      conditions have led to greatly divergent results among different studies.
      Consensus investigation to identify genes and gene sets enriched in multiple
      studies is important for revealing differential gene expression intrinsic to
      human CM differentiation independent of the above variables, but reliable methods
      of conducting such comparison are lacking. We examined differential gene
      expression between hESC and hESC-CMs from multiple microarray studies. For single
      gene analysis, we identified genes that were expressed at increased levels in
      hESC-CMs in seven datasets and which have not been previously highlighted. For
      gene set analysis, we developed a new algorithm, consensus comparative analysis
      (CSSCMP), capable of evaluating enrichment of gene sets from heterogeneous data
      sources. Based on both theoretical analysis and experimental validation, CSSCMP
      is more efficient and less susceptible to experimental variations than
      traditional methods. We applied CSSCMP to hESC-CM microarray data and revealed
      novel gene set enrichment (e.g., glucocorticoid stimulus), and also identified
      genes that might mediate this response. Our results provide important molecular
      information intrinsic to hESC-CM differentiation. Data and Matlab codes can be
      downloaded from S1 Data. 

PMID- 25938588
TI  - Systematic Literature Review and Meta-Analysis of Renal Function in Human
      Immunodeficiency Virus (HIV)-Infected Patients Treated with Atazanavir (ATV)
      Based Regimens.
AB  - Some HIV antiretroviral therapies (ART) have been associated with renal
      toxicities, which become of increasing concern as HIV-infected patients age and
      develop comorbidities. The objective of this study was to evaluate the relative
      impact of atazanavir (ATV)-based regimens on the renal function of adult patients
      with HIV. We conducted a systematic literature review by searching PubMed,
      EMBASE, Cochrane library, and the CRD from 2000 until March 2013. Major HIV
      related conferences occurring in the past two years were also searched. All
      randomized clinical trials and large cohort studies assessing renal function in
      treatment-naive and/or treatment-experienced HIV patients on ATV-based regimens
      were included. Fixed-effect mixed-treatment network analyses were carried out on
      the most frequently reported renal outcomes. 23 studies met the inclusion
      criteria, and change in estimated glomerular filtration rate (eGFR) from baseline
      to 48 weeks was identified as the main outcome. Two networks including,
      respectively, six studies (using the Cockcroft-Gault method) and four studies
      (using MDRD and CKD-EPI) were analysed. With CG network, ATV/r + TDF/FTC was
      associated with lower impact on the decline of eGFR than ATV/cobicistat + TDF/FTC
      but with higher decrease in eGFR than ATV/r + ABC/3TC (difference in mean change
      from baseline in eGFR respectively +3.67 and -3.89). The use of ATV/cobicistat +
      TDF/FTC led to a similar decline in eGFR as EVG/cobicistat/TDF/FTC. With respect
      to third agents combined with TDF/FTC, ATV/r had a lower increase in eGFR in
      comparison to EFV, and no difference was shown when compared to SQV/r and DRV/r.
      The effect of ATV-based regimens on renal function at 48 weeks appears similar to
      other ART regimens and appears to be modest regardless of boosting agent or
      backbone, although TDF containing backbones consistently leads to greater decline
      in eGFR.

PMID- 25938589
TI  - Plasma Levels of microRNA-145 Are Associated with Severity of Coronary Artery
      Disease.
AB  - BACKGROUND AND OBJECTIVE: MicroRNAs (miRNAs) have been shown to be associated
      with various physiological and pathological conditions, including inflammation
      and cardiovascular disease, but little is known about their relationship with the
      presence of coronary artery disease (CAD) and disease severity. METHODS: A total
      of 195 consecutive subjects who underwent coronary angiography for chest pain
      evaluation were enrolled in this study. In CAD patients severity of coronary
      lesions was assessed by the number of diseased vessels and the Synergy between
      PCI with Taxus and Cardiac surgery score (SYNTAX score). Plasma levels of miRNA
      145 were quantified by real-time quantitative polymerase chain reaction test, and
      logarithmic transformation of miRNA-145 levels (Ln_miRNA-145) was used for
      analyses due to its skewed distribution. RESULTS: Of the 195 total subjects 167
      patients were diagnosed as having CAD. Ln_miRNA-145 was significantly lower in
      CAD patients compared with the non-CAD group (-6.11 +/- 0.92 vs. -5.06 +/- 1.25;
      p < 0.001). In multivariable linear regression analyses CAD was significantly
      associated with lower Ln_miRNA-145 (Estimate, -0.50; standard error (SE), 0.11; p
      < 0.0001). Furthermore, among CAD patients, three-vessel disease, higher SYNTAX
      scores and STEMI were significantly associated with lower Ln_miRNA-145
      ([Estimate, -0.40; SE, 0.07; p < 0.0001]; [Estimate, -0.02, SE, 0.10; p = 0.005]
      and [Estimate, -0.35, SE, 0.10; p < 0.001] respectively). CONCLUSIONS: Lower
      plasma levels of miRNA-145 were significantly associated with the presence as
      well as severity of CAD. As a potential biomarker for CAD, plasma miRNA-145 may
      be useful in predicting CAD and its severity in patients presenting with chest
      pain.

PMID- 25938590
TI  - Sphingolipid metabolism correlates with cerebrospinal fluid Beta amyloid levels
      in Alzheimer's disease.
AB  - Sphingolipids are important in many brain functions but their role in Alzheimer's
      disease (AD) is not completely defined. A major limit is availability of fresh
      brain tissue with defined AD pathology. The discovery that cerebrospinal fluid
      (CSF) contains abundant nanoparticles that include synaptic vesicles and large
      dense core vesicles offer an accessible sample to study these organelles, while
      the supernatant fluid allows study of brain interstitial metabolism. Our
      objective was to characterize sphingolipids in nanoparticles representative of
      membrane vesicle metabolism, and in supernatant fluid representative of
      interstitial metabolism from study participants with varying levels of cognitive
      dysfunction. We recently described the recruitment, diagnosis, and CSF collection
      from cognitively normal or impaired study participants. Using liquid
      chromatography tandem mass spectrometry, we report that cognitively normal
      participants had measureable levels of sphingomyelin, ceramide, and
      dihydroceramide species, but that their distribution differed between
      nanoparticles and supernatant fluid, and further differed in those with cognitive
      impairment. In CSF from AD compared with cognitively normal participants: a)
      total sphingomyelin levels were lower in nanoparticles and supernatant fluid; b)
      levels of ceramide species were lower in nanoparticles and higher in supernatant
      fluid; c) three sphingomyelin species were reduced in the nanoparticle fraction.
      Moreover, three sphingomyelin species in the nanoparticle fraction were lower in
      mild cognitive impairment compared with cognitively normal participants. The
      activity of acid, but not neutral sphingomyelinase was significantly reduced in
      the CSF from AD participants. The reduction in acid sphingomylinase in CSF from
      AD participants was independent of depression and psychotropic medications. Acid
      sphingomyelinase activity positively correlated with amyloid beta42 concentration
      in CSF from cognitively normal but not impaired participants. In dementia,
      altered sphingolipid metabolism, decreased acid sphingomyelinase activity and its
      lost association with CSF amyloid beta42 concentration, underscores the potential
      of sphingolipids as disease biomarkers, and acid sphingomyelinase as a target for
      AD diagnosis and/or treatment. 

PMID- 25938591
TI  - Simplified Human Neutrophil Extracellular Traps (NETs) Isolation and Handling.
AB  - Neutrophil Extracellular Traps (NETs) have been recently identified as part of
      the neutrophil's antimicrobial armamentarium. Apart from their role in fighting
      infections, recent research has demonstrated that they may be involved in many
      other disease processes, including cancer progression. Isolating purified NETs is
      a crucial element to allow the study of these functions. In this video, we
      demonstrate a simplified method of cell free NET isolation from human whole blood
      using readily available reagents. Isolated NETs can then be used for
      immunofluorescence staining, blotting or various functional assays. This enables
      an assessment of their biologic properties in the absence of the potential
      confounding effects of neutrophils themselves. A density gradient separation
      technique is employed to isolate neutrophils from healthy donor whole blood.
      Isolated neutrophils are then stimulated by phorbol 12-myristate 13-acetate (PMA)
      to induce NETosis. Activated neutrophils are then discarded, and a cell-free NET
      stock is obtained. We then demonstrate how isolated NETs can be used in an
      adhesion assay with A549 human lung cancer cells. The NET stock is used to coat
      the wells of a 96 well cell culture plate O/N, and after ensuring an adequate NET
      monolayer formation on the bottom of the wells, CFSE labeled A549 cells are
      added. Adherent cells are quantified using a Nikon TE300 fluorescent microscope.
      In some wells, 1000U DNAse1 is added 10 min before counting to degrade NETs. 

PMID- 25938592
TI  - The Diagnostic Cascade of Incidental Findings: A Teachable Moment.

PMID- 25938593
TI  - Anisotropic In-Plane Conductivity and Dichroic Gold Plasmon Resonance in Plasma
      Assisted ITO Thin Films e-Beam-Evaporated at Oblique Angles.
AB  - ITO thin films have been prepared by electron beam evaporation at oblique angles
      (OA), directly and while assisting their growth with a downstream plasma. The
      films microstructure, characterized by scanning electron microscopy, atomic force
      microscopy, and glancing incidence small-angle X-ray scattering, consisted of
      tilted and separated nanostructures. In the plasma assisted films, the tilting
      angle decreased and the nanocolumns became associated in the form of bundles
      along the direction perpendicular to the flux of evaporated material. The
      annealed films presented different in-depth and sheet resistivity as confirmed by
      scanning conductivity measurements taken for the individual nanocolumns. In
      addition, for the plasma-assisted thin films, two different sheet resistance
      values were determined by measuring along the nanocolumn bundles or the
      perpendicular to it. This in-plane anisotropy induces the electrochemical
      deposition of elongated gold nanostructures. The obtained Au-ITO composite thin
      films were characterized by anisotropic plasmon resonance absorption and a
      dichroic behavior when examined with linearly polarized light. 

PMID- 25938594
TI  - Regulation of hepatocyte growth factor in mice with pneumonia by peptidases and
      trans-alveolar flux.
AB  - Hepatocyte growth factor (HGF) promotes lung epithelial repair after injury.
      Because prior studies established that human neutrophil proteases inactivate HGF
      in vitro, we predicted that HGF levels decrease in lungs infiltrated with
      neutrophils and that injury is less severe in lungs lacking HGF-inactivating
      proteases. After establishing that mouse neutrophil elastase cleaves mouse HGF in
      vitro, we tested our predictions in vivo by examining lung pathology and HGF in
      mice infected with Mycoplasma pulmonis, which causes neutrophilic
      tracheobronchitis and pneumonia. Unexpectedly, pneumonia severity was similar in
      wild type and dipeptidylpeptidase I-deficient (Dppi-/-) mice lacking neutrophil
      serine protease activity. To assess how this finding related to our prediction
      that Dppi-activated proteases regulate HGF levels, we measured HGF in serum,
      bronchoalveolar lavage fluid, and lung tissue from Dppi(+/+) and Dppi(-/-) mice.
      Contrary to prediction, HGF levels were higher in lavage fluid from infected
      mice. However, serum and tissue concentrations were not different in infected and
      uninfected mice, and HGF lung transcript levels did not change. Increased HGF
      correlated with increased albumin in lavage fluid from infected mice, and
      immunostaining failed to detect increased lung tissue expression of HGF in
      infected mice. These findings are consistent with trans-alveolar flux rather than
      local production as the source of increased HGF in lavage fluid. However, levels
      of intact HGF from infected mice, normalized for albumin concentration, were two
      fold higher in Dppi(-/-) versus Dppi(+/+) lavage fluid, suggesting regulation by
      Dppi-activated proteases. Consistent with the presence of active HGF, increased
      expression of activated receptor c-Met was observed in infected tissues. These
      data suggest that HGF entering alveoli from the bloodstream during pneumonia
      compensates for destruction by Dppi-activated inflammatory proteases to allow HGF
      to contribute to epithelial repair.

PMID- 25938595
TI  - Strategies to rescue the consequences of inducible arginase-1 deficiency in mice.
AB  - Arginase-1 catalyzes the conversion of arginine to ornithine and urea, which is
      the final step of the urea cycle used to remove excess ammonia from the body.
      Arginase-1 deficiency leads to hyperargininemia in mice and man with severe
      lethal consequences in the former and progressive neurological impairment to
      varying degrees in the latter. In a tamoxifen-induced arginase-1 deficient mouse
      model, mice succumb to the enzyme deficiency within 2 weeks after inducing the
      knockout and retain <2 % enzyme in the liver. Standard clinical care regimens for
      arginase-1 deficiency (low-protein diet, the nitrogen-scavenging drug sodium
      phenylbutyrate, ornithine supplementation) either failed to extend lifespan
      (ornithine) or only minimally prolonged lifespan (maximum 8 days with low-protein
      diet and drug). A conditional, tamoxifen-inducible arginase-1 transgenic mouse
      strain expressing the enzyme from the Rosa26 locus modestly extended lifespan of
      neonatal mice, but not that of 4-week old mice, when crossed to the inducible
      arginase-1 knockout mouse strain. Delivery of an arginase-1/enhanced green
      fluorescent fusion construct by adeno-associated viral delivery (rh10 serotype
      with a strong cytomegalovirus-chicken beta-actin hybrid promoter) rescued about
      30% of male mice with lifespan prolongation to at least 6 months, extensive
      hepatic expression and restoration of significant enzyme activity in liver. In
      contrast, a vector of the AAV8 serotype driven by the thyroxine-binding globulin
      promoter led to weaker liver expression and did not rescue arginase-1 deficient
      mice to any great extent. Since the induced arginase-1 deficient mouse model
      displays a much more severe phenotype when compared to human arginase-1
      deficiency, these studies reveal that it may be feasible with gene therapy
      strategies to correct the various manifestations of the disorder and they provide
      optimism for future clinical studies. 

PMID- 25938596
TI  - Correction: microbial community structure and diversity in an integrated system
      of anaerobic-aerobic reactors and a constructed wetland for the treatment of
      tannery wastewater in Modjo, Ethiopia.

PMID- 25938597
TI  - Seasonal variation of human semen parameters: A retrospective study in Italy.
AB  - INTRODUCTION: Human infertility is a common condition secondary to many primary
      or secondary causes. As for these latter, different seasonal and climatic
      patterns have been hypothesized to play a role. The aim of this study was to
      assess the presence of a possible seasonal pattern in the functional parameters
      of semen samples maintained in a large tertiary center database. MATERIALS AND
      METHODS: The reports of spermograms of 5188 consecutive subjects, collected at
      the Center for Reproductive Incapacity of the University Hospital of Parma during
      a 11-year period (2003-2014), were retrospectively analyzed. The reports included
      sperm motility, volume, and number, as well as pH, swelling and eosin tests. Data
      of different parameters were analyzed by season of sample collection. The ANOVA
      test was used for the evaluation of continuous variables, after Log
      transformation in case of a non-normal distribution, while chi(2) test was used
      for categorical variables. Moreover, logistic regression analysis was performed,
      to identify factors independently associated with normal sperm motility. RESULTS:
      Compared with the other seasons of the year, a higher sperm motility was found
      during the summer. Moreover, the prevalence of samples with a normal sperm pH
      (7.2-8) was higher during the spring, whilst the volume of sperm was higher in
      winter. Logistic regression analysis showed that normal sperm motility (>40%) was
      independently associated with spring (1.227; 95% CI 1.077-1.507, p = 0.005),
      summer (2.031; 95% CI 1.689-2.442, p < 0.001), swelling test (1.953; 95% CI 1.670
      2.284, p < 0.001), eosin test (2.804; 95% CI 2.477-3.174, p < 0.001), pH (0.507;
      95% CI 0.346-0.743, p < 0.001), LOG-number (2.949; 95% CI 2.470-3.522, p < 0.001)
      and LOG-volume (2.216; 95% CI 1.696-2.894, p < 0.001) of semen. CONCLUSION: This
      study suggests the existence of a positive relationship between some semen
      parameters and seasons.

PMID- 25938598
TI  - Determining Stability in Posterior Wall Acetabular Fractures.
AB  - OBJECTIVES: To determine if the radiographic parameters of femoral head coverage
      by the intact posterior wall, acetabular version, and location of the fracture or
      a history of dislocation were determinates of hip stability in patients with
      posterior wall acetabular fractures. DESIGN: Retrospective review. SETTING: Level
      I trauma hospital. PATIENTS: One hundred eighty-five consecutive patients with
      isolated unilateral posterior wall (OTA 62-A1) acetabular fractures.
      INTERVENTION: Patients underwent dynamic stress fluoroscopic examination under
      general anesthesia to determine hip stability. MAIN OUTCOME MEASUREMENTS: A
      number of radiographic measurements were performed, and an examination under
      anesthesia served as a standard to compare stable versus unstable hips. RESULTS:
      Examination under anesthesia (EUA) determined 116 hips to be stable and 22 hips
      as unstable. Moed and Keith method of wall size measurements and cranial exit
      point of fracture was statistically different between stable and unstable hips.
      Twenty-three percent of the unstable hips had wall sizes less than 20%. Average
      cranial exit point of fracture from dome was 5.0 mm in the unstable group and 9.5
      mm in the stable group, and fractures that extend into the dome demonstrate a
      statistically significant increase in hip instability. CONCLUSIONS: Determination
      of hip stability can be challenging in patients with posterior wall acetabular
      fractures. Our data suggest that the location of the exit point of the fracture
      in relation to the dome of the acetabulum is a radiographic marker that can be
      used to aid physician in determining stability, and wall sizes less than 20% is
      not a reliable indicator of stability. LEVEL OF EVIDENCE: Diagnostic Level II.
      See Instructions for Authors for a complete description of levels of evidence.

PMID- 25938599
TI  - Synthesis of Chiral alpha-Amino Tertiary Boronic Esters by Enantioselective
      Hydroboration of alpha-Arylenamides.
AB  - The rhodium-catalyzed asymmetric hydroboration of alpha-arylenamides with BI-DIME
      as the chiral ligand and (Bpin)2 as the reagent yields for the first time a
      series of alpha-amino tertiary boronic esters in good yields and excellent
      enantioselectivities (up to 99% ee). 

PMID- 25938600
TI  - [Editorial].

PMID- 25938601
TI  - [Management of clinical nutrition].
AB  - Proper management of Clinical Nutrition requires careful planning of the
      resources required to delineate the activities to be performed by each of the
      participants and consider the need for continued evaluation of the results to
      improve. Units of Nutrition and Nutritional Support Teams must have a
      multidisciplinary composition, incorporating professionals with training and
      experience in Clinical Nutrition. Whenever conditions permit and activity of each
      center indicates, the staff's dedication to nutrition must be complete. The
      organization of processes and use of clinical practice protocols facilitates the
      monitoring of the activities carried out by teams of Nutrition. Each stage of a
      process has quality criteria based on scientific knowledge, and some key
      objectives whose degree of achievement can be measured by monitoring quality
      indicators and their comparison with standards. Successive cycles of measurement
      indicators, evaluation and corrective interventions lead to continuous process
      improvement.

PMID- 25938602
TI  - [Implementation of an ERAS program in liver surgery].
AB  - The perioperative management of patients undergoing abdominal surgery has been
      based on traditional concepts and often not supported by scientific evidence.
      Recently there have been several scientific studies showing that some traditional
      procedures for the perioperative management of patients as preoperative fasting,
      bowel preparation, use of naso-gastric tubes, placement of intra-abdominal
      drainage, postoperative fasting etc. They are unnecessary and sometimes
      counterproductive. Perioperative management protocols ERAS or Fast-Track
      (Enhanced Recovery After Surgery) are based on the use in the perioperative
      period of measures that are supported by current scientific evidence. Since 2000
      appear in the scientific literature several works that reflect the application of
      protocols ERAS or Fast- Track in surgery of the digestive system where it's shown
      uniformly, not only the security of your application but also, decreased
      complications and hospital stay. Although initially these protocols were
      described in colorectal surgery, due to the good results obtained, the
      application of these protocols has rapidly expanded to other surgical specialties
      such as thoracic surgery, Urology, Gynaecology, etc. In all these specialties has
      unanimously showing improved postoperative recovery with ERAS application
      protocols. The purpose of this paper is twofold. On the one hand examine the
      scientific evidence that exists today on the most important elements of an ERAS
      program and present preliminary results of the implementation of a program ERAS
      in our hospital.

PMID- 25938603
TI  - [Continuity of nutritional care at discharge in the era of ICT].
AB  - Telemedicine represents the union of information technology and telecommunication
      services in health. This allows the improvement of health care, especially in
      underserved areas, bringing professionals working in continuing education and
      improving patient care at home. The application of telemedicine in various
      hospital complexes, clinics and health centers, has helped to provide a better
      service, within the parameters of efficiency, effectiveness, cost-benefit, with
      increasing satisfaction of medical staff and patients. The development and
      application of various types of telemedicine, the technological development of
      audio, text, video and data, and constant improvement of infrastructure in
      telecommunications, have favored the expansion and development of telemedicine in
      various medical specialties. The use of electronic health records by different
      health professionals can have a positive impact on the care provided to patients.
      This should also be supported by the development of better health policies, legal
      security and greater awareness in health professionals and patients regarding the
      potential benefits. Regarding the clinical activity in Nutrition, new
      technologies also provide an opportunity to improve in various educational,
      preventive, diagnostic and treatment aspects, including shared track between
      Nutrition Units and Primary Care Teams, for patients who need home nutritional
      care at, with shared protocols, providing teleconsultation in required cases and
      avoiding unnecessary travel to hospital.

PMID- 25938604
TI  - [Standardization of hospital feeding].
AB  - INTRODUCTION: Normalization can be understood as the establishing measures
      against repetitive situations through the development, dissemination, and
      application of technical design documents called standards. In Andalusia there
      are 45 public hospitals with 14,606 beds, and in which 11,700 full pensions / day
      are served. The Working Group on Hospital Food Standardization of the Andalusian
      Society for Clinical Nutrition and Dietetics, started in 2010, working on the
      certification of suppliers, product specifications, and meals technical card.
      AIMS: - Develop a specific tool to help improving food safety through the
      certification of their suppliers. - Develop a standardized technical
      specifications of foodstuffs necessary for the development of menus established
      codes diets Andalusian hospitals document. - Develop a catalog of data sheets
      plates of hospital meals, to homogenize menus, respecting local and unifying
      criteria for qualitative and quantitative ingredients. METHODS: - Providing
      documentation and studying of several public hospitals in Andalusia: * Product
      specifications and certification of suppliers. * International standards
      certification and distribution companies. * Legislation. * Data sheets for the
      menu items. * Specifications of different product procurement procedures. -
      Development of the draft standard HOSPIFOOD(r), and approval of the version
      "0.0". - Training course for auditors to this standard. - Development of a raw
      materials catalog as technical cards. - Meals Technical cards review and election
      of the ones which will be part of the document. RESULTS: After nearly three years
      of work, we have achieved the following products: - Standardized database of
      technical specifications for the production of food dietary codes for: fish,
      seafood, meat and meat products, meats and pates, ready meals, bread and
      pastries, preserves, milk and dairy products, oils, cereals, legumes ,
      vegetables, fruits, fresh and frozen vegetables, condiments and spices. -
      Standardized database of technical cards for meals containing the following data:
      SAS Code, Province, Hospital, name plate, ingredients (g), edible ingredients (g)
      kcal, Proteins, HC, Fat and Fiber. - HOSPIFOOD(r) standard certification for food
      providers in hospitals, school cafeterias and other institutions of social
      restoration. CONCLUSION: Patients expect food that is offered during the stay in
      the hospital, meet basic standards of quality and safety, and therefore it is
      necessary to design and develop control systems from the award and / or
      acquisition of food (raw materials and finished) products which subsequently
      become part of the menu that is offered as part of their treatment. To avoid the
      effect of fraudulent practice in public health, it's needed to ensure the quality
      and safety of the food from the origin and establish the standards for
      acquisition and subsequent use of it.

PMID- 25938605
TI  - [Applying standards of pharmaceutical practice in nutritional therapy cancer
      patient].
AB  - Malnutrition in cancer patients is associated with a poor prognosis, weight loss
      being an important predictor of mortality. The cancer and its treatment have a
      great impact on nutritional status, so by applying nutritional therapy can
      improve quality of life, prognosis and functional status. The application of
      standards of practice this therapy in cancer patients can reduce variability of
      interventions and promote efficient, safe and quality use. Being the hospital
      pharmacist as part of the nutritional support team a key in optimizing nutrition
      therapy through four strategic partner roles: clinical, technical, operational
      and manager.

PMID- 25938606
TI  - [The patient's opinion matters: experience in the nutritional care in an ALS
      multidisciplinary team].
AB  - Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease which has no
      cure, so the treatment will be symptomatic in a Multidisciplinary Unit. It is
      composed of professionals, experts in patient care, with an interdisciplinary
      vision in order to act in a coordinated manner depending on the different
      situations which may arise over the course of the disease. There are several
      studies showing improved survival in patients treated within the framework of a
      multidisciplinary team compared to treatment by isolated specialties. An ALS
      Multidisciplinary Unit was created in 2004 in the University Hospital of
      Bellvitge (HUB). It is composed of a neurologist, pulmonologist, nutritionist,
      endocrinologist, rehabilitation, physical therapist, psychologist, social worker,
      nurse manager, speech therapist and an administrative worker. To assess the
      impact of the multidisciplinary care of our program 418 patients diagnosed with
      ALS were evaluated, 84 patients who had been treated by general neurology and 334
      who had been treated under a model of multidisciplinary care. Patients who were
      treated in the unit of multidisciplinary care had a median survival of 1246 days
      (IC 1109-1382), 104 days above the median 1148 days of those followed by a
      general neurology consultation (CI 998-1297). This difference was statistically
      significant (log-rank 10,8; p= 0.008). This benefit was independent of having
      received treatment with riluzole, non-invasive mechanical ventilation or
      percutaneous gastrostomy. Nutritional assessment was performed on the first visit
      and all subsequent controls. It is important to do anthropometric measurements
      and detect unintentional weight loss and its possible precipitating causes in
      order to establish the appropriate nutritional treatment. The exploration of
      dysphagia allows a determination of the appropriate dietary advice, the
      introduction of thickeners to adjust the texture of food or nutritional
      supplementation with high-calorie formulas to prevent or correct weight loss. If
      these measures are not sufficient or there is the risk of failure of respiratory
      function, early gastrostomy placement will be indicated. The analysis of 140 ALS
      patients (92 controls and 48 with radiologic percutaneous gastrostomy) showed no
      difference in mean survival time between groups (32 vs 33.9 months, log Rank 1.86
      p=0.39). Any patient had major complications. Despite not find changes in
      survival, the use of gastrostomy should be understood as a treatment to improve
      the quality of life and well-being of the patient. Psychosocial support of the
      person and the family environment is essential to integrate all the changes and
      situations that arise in the course of the disease. This should start from
      diagnosis as early intervention contributes to improved training, preventing
      situations of deterioration and helping coping with the dependency process. It is
      also possible to use technology and social media to complement the classic care
      model. In the case of the HUB ALS Multidisciplinary Unit, affected individuals
      and their families have the resources of the Aula Paciente and ALS blog, created
      with the objective of providing opportunities for dialogue between patients,
      families and caregivers. The satisfaction degree of the patients with the care
      provided by the ALS Multidisciplinary Unit on service accessibility, information
      received and the quality of care was assessed globally as good in 52.8% or very
      good in 29, 2% of patients. CONCLUSION: Attention for the ALS affected person
      must be considered within the framework of a multidisciplinary team made up of
      all the professionals who go to intervene throughout the disease process in order
      to provide increased survival with the best care and quality of life.

PMID- 25938607
TI  - [Quality, Innovation and Technological Development in Enteral Nutrition in the
      XXI Century].
AB  - This work synthesis the quality evolution as well as innovation and technological
      advances that have been proven in healthcare area and specifically in enteral
      nutrition field. Clarifying the most relevant landmarks and the best
      representative characteristics of these advances.

PMID- 25938608
TI  - The +37 kb Cebpa Enhancer Is Critical for Cebpa Myeloid Gene Expression and
      Contains Functional Sites that Bind SCL, GATA2, C/EBPalpha, PU.1, and Additional
      Ets Factors.
AB  - The murine Cebpa gene contains an evolutionarily conserved 453 bp enhancer
      located at +37 kb that, together with its promoter, directs expression to myeloid
      progenitors and to long-term hematopoietic stem cells in transgenic mice. In
      human acute myeloid leukemia cases, the enhancer lacks point mutations but binds
      the RUNX1-ETO oncoprotein. The enhancer contains the H3K4me1 and H3K27Ac histone
      modifications, denoting an active enhancer, at progressively increasing levels as
      long-term hematopoietic stem cells transition to granulocyte-monocyte
      progenitors. We previously identified four enhancer sites that bind RUNX1 and
      demonstrated that their integrity is required for maximal enhancer activity in
      32Dcl3 myeloid cells. The +37 kb Cebpa enhancer also contains C/EBP, Ets factor,
      Myb, GATA, and E-box consensus sites conserved in the human +42 kb CEBPA
      enhancer. Mutation of the two C/EBP, seven Ets, one Myb, two GATA, or two E-box
      sites reduces activity of an enhancer-promoter reporter in 32Dcl3 cells. In 293T
      gel shift assays, exogenous C/EBPalpha binds both C/EBP sites, c-Myb binds the
      Myb site, PU.1 binds the second Ets site, PU.1, Fli-1, ERG, and Ets1 bind the
      sixth Ets site, GATA2 binds both GATA sites, and SCL binds the second E-box.
      Endogenous hematopoietic RUNX1, PU.1, Fli-1, ERG, C/EBPalpha, GATA2, and SCL were
      previously shown to bind the enhancer, and we find that endogenous PU.1 binds the
      second Ets site in 32Dcl3 cells. Using CRISPR/Cas9, we developed 32Dcl3 lines in
      which the wild-type enhancer alleles are replaced with a variant mutant in the
      seven Ets sites. These lines have 20-fold reduced Cebpa mRNA when cultured in IL
      3 or G-CSF, demonstrating a critical requirement for enhancer integrity for
      optimal Cebpa expression. In addition, these results indicate that the +37 kb
      Cebpa enhancer is the focus of multiple regulatory transcriptional pathways that
      impact its expression during normal hematopoiesis and potentially during myeloid
      transformation. 

PMID- 25938609
TI  - Ready, steady, go! A sugar hit starts the race to shoot branching.
AB  - In the classical theory of apical dominance, auxin depletion from the stem
      releases bud dormancy. Recent studies have revealed a poor correlation between
      the initial bud release and auxin depletion from the stem after decapitation.
      Sucrose mobility in plants and its accumulation in buds correlates well with the
      onset of bud release and is able to trigger bud outgrowth. The diversion of
      sugars away from axillary buds decreases bud release even where hormones are at
      levels generally considered conducive to bud release. This impact of sugars on
      bud outgrowth may be mediated by specific sugar and hormonal signalling pathways.

PMID- 25938610
TI  - Explicitly guided attentional bias modification promotes attentional
      disengagement from negative stimuli.
AB  - Previous studies have shown that attentional bias modification (ABM) is effective
      in reducing negative attentional biases. However, the mechanisms underlying how
      ABM effectively reduces negative attentional biases are still unclear. In the
      present study, we conducted an ABM procedure that included a 3-day training
      session with a sample of nonclinical participants (N = 40) to investigate the
      effect of ABM on emotional and nonemotional attentional biases. Participants
      completed a modified dot-probe task with 2 different instructions (explicit or
      standard) during the training; their attentional biases were tested before and
      after the training. Only participants trained with explicit instructions showed a
      reduction in negative attentional biases in dot-probe task and an improvement in
      attentional disengagement from negative stimuli in gap-overlap task. On the other
      hand, attention toward nonemotional stimuli was only marginally improved by
      training with both explicit and standard instructions. These results indicate
      that explicit instructions may promote ABM training.

PMID- 25938611
TI  - Emotional competence and extrinsic emotion regulation directed toward an
      ostracized person.
AB  - Positive interpersonal relationships hinge on individuals' competence in
      regulating others' emotions as well as their own. Nevertheless, little is known
      about the relationship between emotional competence and specific interpersonal
      behaviors. In particular, it is unclear which situations require emotional
      competence for extrinsic emotion regulation and whether emotionally competent
      individuals actually attempt to regulate others' emotions. To clarify these
      issues, the current investigation examined the relationship between emotional
      competence and extrinsic emotion regulation directed toward an ostracized person.
      The results of Study 1 (N = 39) indicated that interpersonal emotional competence
      (competence related to others' emotions) was positively associated with
      participants' efforts to relieve the ostracized person's sadness. In Study 2 (N =
      120), this relationship was moderated by the ostracized person's emotional
      expression. In particular, participants with high interpersonal emotional
      competence were more likely to attempt to regulate the sadness of ostracized
      individuals who expressed neutral affect. In contrast, when the ostracized person
      expressed sadness, there were no significant relationships between high or low
      interpersonal emotional competence and extrinsic emotion regulation behavior.
      These results offer novel insight into how emotionally competent individuals use
      their competence to benefit others.

PMID- 25938612
TI  - A new look at emotion perception: Concepts speed and shape facial emotion
      recognition.
AB  - Decades ago, the "New Look" movement challenged how scientists thought about
      vision by suggesting that conceptual processes shape visual perceptions.
      Currently, affective scientists are likewise debating the role of concepts in
      emotion perception. Here, we utilized a repetition-priming paradigm in
      conjunction with signal detection and individual difference analyses to examine
      how providing emotion labels-which correspond to discrete emotion concepts
      affects emotion recognition. In Study 1, pairing emotional faces with emotion
      labels (e.g., "sad") increased individuals' speed and sensitivity in recognizing
      emotions. Additionally, individuals with alexithymia-who have difficulty labeling
      their own emotions-struggled to recognize emotions based on visual cues alone,
      but not when emotion labels were provided. Study 2 replicated these findings and
      further demonstrated that emotion concepts can shape perceptions of facial
      expressions. Together, these results suggest that emotion perception involves
      conceptual processing. We discuss the implications of these findings for
      affective, social, and clinical psychology.

PMID- 25938613
TI  - Effectiveness of internet-based affect induction procedures: A systematic review
      and meta-analysis.
AB  - Procedures used to induce affect in a laboratory are effective and well
      validated. Given recent methodological and technological advances in Internet
      research, it is important to determine whether affect can be effectively induced
      using Internet methodology. We conducted a meta-analysis and systematic review of
      prior research that has used Internet-based affect induction procedures, and
      examined potential moderators of the effectiveness of affect induction
      procedures. Twenty-six studies were included in final analyses, with 89
      independent effect sizes. Affect induction procedures effectively induced general
      positive affect, general negative affect, fear, disgust, anger, sadness, and
      guilt, but did not significantly induce happiness. Contamination of other
      nontarget affect did not appear to be a major concern. Video inductions resulted
      in greater effect sizes. Overall, results indicate that affect can be effectively
      induced in Internet studies, suggesting an important venue for the acceleration
      of affective science. (PsycINFO Database Record 

PMID- 25938614
TI  - Intensive meditation training influences emotional responses to suffering.
AB  - Meditation practices purportedly help people develop focused and sustained
      attention, cultivate feelings of compassionate concern for self and others, and
      strengthen motivation to help others who are in need. We examined the impact of 3
      months of intensive meditative training on emotional responses to scenes of human
      suffering. Sixty participants were assigned randomly to either a 3-month
      intensive meditation retreat or a wait-list control group. Training consisted of
      daily practice in techniques designed to improve attention and enhance
      compassionate regard for others. Participants viewed film scenes depicting human
      suffering at pre- and posttraining laboratory assessments, during which both
      facial and subjective measures of emotion were collected. At post-assessment,
      training group participants were more likely than controls to show facial
      displays of sadness. Trainees also showed fewer facial displays of rejection
      emotions (anger, contempt, disgust). The groups did not differ on the likelihood
      or frequency of showing these emotions prior to training. Self-reported sympathy-
      but not sadness or distress--predicted sad behavior and inversely predicted
      displays of rejection emotions in trainees only. These results suggest that
      intensive meditation training encourages emotional responses to suffering
      characterized by enhanced sympathetic concern for, and reduced aversion to, the
      suffering of others.

PMID- 25938615
TI  - Finding the middle ground: Curvilinear associations between positive affect
      variability and daily cortisol profiles.
AB  - There is growing evidence that there are stable and meaningful individual
      differences in how much people vary in their experience of positive affect (PA),
      which in turn may have implications for health and well-being. Does such PA
      variability play a role in physiological processes potentially related to stress
      and health, such as daily cortisol profiles? We explored this question by
      examining whether PA variability across and within days in middle-aged adults
      (Study 1) and across weeks in older adults (Study 2) was associated with daily
      salivary cortisol profiles. In both studies, individuals who exhibited moderate
      PA variability demonstrated more favorable cortisol profiles, such as lower
      levels of cortisol and steeper slopes. Interestingly, for middle-aged adults
      (Study 1), high levels of within-day PA variability were associated with the
      least favorable cortisol profiles, whereas for older adults (Study 2), low levels
      of across-week PA variability were associated with the least favorable cortisol
      profiles. Collectively, these findings provide some of the first evidence that PA
      variability is related to daily cortisol profiles, suggesting that it may be
      better to experience a moderate degree of positive affect variability. Too much
      or too little variability, however, may be problematic, potentially carrying
      negative implications for stress-related physiological responding.

PMID- 25938616
TI  - Rapid temporal accumulation in spider fear: Evidence from hierarchical drift
      diffusion modelling.
AB  - Fear can distort sense of time--making time seem slow or even stand still. Here,
      I used hierarchical drift diffusion modeling (HDDM; Vandekerckhove, Tuerlinckx, &
      Lee, 2008, 2011; Wiecki, Sofer, & Frank, 2013) to test the idea that temporal
      accumulation speeds up during fear. Eighteen high fearful and 23 low fearful
      participants judged the duration of both feared stimuli (spiders) and nonfeared
      stimuli (birds) in a temporal bisection task. The drift diffusion modeling
      results support the main hypothesis. In high but not low fearful individuals,
      evidence accumulated more rapidly toward a long duration decision-drift rates
      were higher-for spiders compared with birds. This result and further insights
      into how fear affects time perception would not have been possible on the basis
      of analyses of choice proportion data alone. Further results were interpreted in
      the context of a recent 2-stage model of time perception (Balci & Simen, 2014).
      The results highlight the usefulness of diffusion modeling to test process-based
      explanations of disordered cognition in emotional disorders.

PMID- 25938617
TI  - Childhood Sleepwalking and Sleep Terrors: A Longitudinal Study of Prevalence and
      Familial Aggregation.
AB  - IMPORTANCE: Childhood sleepwalking and sleep terrors are 2 parasomnias with a
      risk of serious injury for which familial aggregation has been shown. OBJECTIVES:
      To assess the prevalence of sleepwalking and sleep terrors during childhood; to
      investigate the link between early sleep terrors and sleepwalking later in
      childhood; and to evaluate the degree of association between parental history of
      sleepwalking and presence of somnambulism and sleep terrors in children. DESIGN,
      SETTING, AND PARTICIPANTS: Sleep data from a large prospective longitudinal
      cohort (the Quebec Longitudinal Study of Child Development) of 1940 children born
      in 1997 and 1998 in the province were studied from March 1999 to March 2011. MAIN
      OUTCOMES AND MEASURES: Prevalence of sleep terrors and sleepwalking was assessed
      yearly from ages 1 1/2 and 2 1/2 years, respectively, to age 13 years through a
      questionnaire completed by the mother. Parental history of sleepwalking was also
      queried. RESULTS: The peak of prevalence was observed at 1 1/2 years for sleep
      terrors (34.4% of children; 95% CI, 32.3%-36.5%) and at age 10 years for
      sleepwalking (13.4%; 95% CI, 11.3%-15.5%). As many as one-third of the children
      who had early childhood sleep terrors developed sleepwalking later in childhood.
      The prevalence of childhood sleepwalking increases with the degree of parental
      history of sleepwalking: 22.5% (95% CI, 19.2%-25.8%) for children without a
      parental history of sleepwalking, 47.4% (95% CI, 38.9%-55.9%) for children who
      had 1 parent with a history of sleepwalking, and 61.5% (95% CI, 42.8%-80.2%) for
      children whose mother and father had a history of sleepwalking. Moreover,
      parental history of sleepwalking predicted the incidence of sleep terrors in
      children as well as the persistent nature of sleep terrors. CONCLUSIONS AND
      RELEVANCE: These findings substantiate the strong familial aggregation for the 2
      parasomnias and lend support to the notion that sleepwalking and sleep terrors
      represent 2 manifestations of the same underlying pathophysiological entity.

PMID- 25938618
TI  - WITHDRAWN. Antiviral treatment for Bell's palsy (idiopathic facial paralysis).
AB  - BACKGROUND: Corticosteroids are widely used in the treatment of idiopathic facial
      paralysis (Bell's palsy), but the effectiveness of additional treatment with an
      antiviral agent is uncertain. Significant morbidity can be associated with severe
      cases of Bell's palsy. OBJECTIVES: To assess the effects of antiviral treatments
      alone or in combination with any other therapy for Bell's palsy. SEARCH METHODS:
      On 7 October 2014 we searched the Cochrane Neuromuscular Disease Group
      Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, DARE, NHS EED, and HTA.
      We also reviewed the bibliographies of the identified trials and contacted trial
      authors and known experts in the field and relevant drug companies to identify
      additional published or unpublished data. We searched clinical trials registries
      for ongoing studies. SELECTION CRITERIA: We considered randomised controlled
      trials or quasi-randomised controlled trials of antivirals with and without
      corticosteroids versus control therapies for the treatment of Bell's palsy. We
      excluded trials that had a high risk of bias in several domains. DATA COLLECTION
      AND ANALYSIS: Pairs of authors independently assessed trials for relevance,
      eligibility, and risk of bias, using standard Cochrane procedures. MAIN RESULTS:
      Eleven trials, including 2883 participants, met the inclusion criteria and are
      included in the final analysis. We added four studies to the previous review for
      this update. Some of the trials were small, and a number were at high or unclear
      risk of bias. Other trials did not meet current best standards in allocation
      concealment and blinding. Incomplete recoveryWe found no significant benefit from
      adding antivirals to corticosteroids in comparison with corticosteroids alone for
      people with Bell's palsy (risk ratio (RR) 0.69, 95% confidence interval (CI) 0.47
      to 1.02, n = 1715). For people with severe Bell's palsy (House-Brackmann scores
      of 5 and 6 or the equivalent in other scales), we found a reduction in the rate
      of incomplete recovery at month six when antivirals plus corticosteroids were
      used (RR 0.64, 95% CI 0.41 to 0.99, n = 478). The outcome for the participants
      receiving corticosteroids alone was significantly better than for those receiving
      antivirals alone (RR 2.09, 95% CI 1.36 to 3.20, n = 1169). The treatment effect
      of placebo was significantly lower than that of antivirals plus corticosteroids
      (RR 0.56, 95% CI 0.41 to 0.76, n = 658). Antivirals alone had a non-significant
      detrimental effect on the outcome compared with placebo (RR 1.10, 95% CI 0.87 to
      1.40, n = 658). Motor synkinesis or crocodile tearsIn three trials comparing
      antivirals and corticosteroids with corticosteroids and placebo that assessed
      this outcome, we found a significant difference in long-term sequelae in favour
      or antivirals plus corticosteroids (RR 0.73, 95% CI 0.54 to 0.99, n = 869). Three
      trials comparing antivirals alone with corticosteroids alone investigating this
      outcome showed fewer sequelae with corticosteroids (RR 1.44, 95% CI 1.11 to 1.85,
      n = 873). We found no data on long-term sequelae for other comparisons. Adverse
      events Adverse event data were available in three studies giving comparison data
      on 1528 participants. None of the four comparisons (antivirals plus
      corticosteroids versus corticosteroids plus placebo or no treatment; antivirals
      versus corticosteroids; antivirals plus corticosteroids versus placebo;
      antivirals versus placebo) showed significant differences in adverse events
      between treatment and control arms. We could find no correlation with specific
      treatment within these results. AUTHORS' CONCLUSIONS: Moderate-quality evidence
      from randomised controlled trials showed no additional benefit from the
      combination of antivirals with corticosteroids compared to corticosteroids alone
      or with placebo, and no benefit from antivirals alone compared to placebo, for
      the treatment of Bell's palsy. Moderate-quality evidence showed a small but just
      significant benefit of combination therapy compared with corticosteroids alone in
      severe Bell's palsy. We found no significant increase in adverse events from the
      use of antivirals compared with either placebo or corticosteroids.

PMID- 25938619
TI  - A Rat Model of Ventricular Fibrillation and Resuscitation by Conventional Closed
      chest Technique.
AB  - A rat model of electrically-induced ventricular fibrillation followed by cardiac
      resuscitation using a closed chest technique that incorporates the basic
      components of cardiopulmonary resuscitation in humans is herein described. The
      model was developed in 1988 and has been used in approximately 70 peer-reviewed
      publications examining a myriad of resuscitation aspects including its physiology
      and pathophysiology, determinants of resuscitability, pharmacologic
      interventions, and even the effects of cell therapies. The model featured in this
      presentation includes: (1) vascular catheterization to measure aortic and right
      atrial pressures, to measure cardiac output by thermodilution, and to
      electrically induce ventricular fibrillation; and (2) tracheal intubation for
      positive pressure ventilation with oxygen enriched gas and assessment of the end
      tidal CO2. A typical sequence of intervention entails: (1) electrical induction
      of ventricular fibrillation, (2) chest compression using a mechanical piston
      device concomitantly with positive pressure ventilation delivering oxygen
      enriched gas, (3) electrical shocks to terminate ventricular fibrillation and
      reestablish cardiac activity, (4) assessment of post-resuscitation hemodynamic
      and metabolic function, and (5) assessment of survival and recovery of organ
      function. A robust inventory of measurements is available that includes - but is
      not limited to - hemodynamic, metabolic, and tissue measurements. The model has
      been highly effective in developing new resuscitation concepts and examining
      novel therapeutic interventions before their testing in larger and
      translationally more relevant animal models of cardiac arrest and resuscitation. 

PMID- 25938620
TI  - Small-molecule two-photon probes for bioimaging applications.

PMID- 25938621
TI  - The influence of mental illness and criminality self-stigmas and racial self
      concept on outcomes in a forensic psychiatric sample.
AB  - OBJECTIVE: Research has increasingly explored mental illness self-stigma: when
      people with mental illness believe that society's negative beliefs are true of
      them. Self-stigma predicts poorer functional and treatment outcomes. Stigma
      research has typically investigated the impact of a single stigma on people,
      without considering the potential effects of multiple stigmatizing labels. People
      with mental illness and a history of criminal conviction, however, may experience
      multiple stigmas related to mental illness and criminal history. This study
      investigated the impact of the combination of multiple stigmatized identities on
      self-esteem, depression, therapeutic alliance, and treatment adherence in a
      forensic psychiatric sample. It extended previous research on mental illness self
      stigma to a forensic psychiatric sample. METHODS: Participants (N = 82) were
      people with mental illness and a history of criminal conviction recruited from
      their treatment sites. Participants completed self-report questionnaires focused
      on mental illness and criminality self-stigma, racial self- concept, self-esteem,
      depression, working alliance, and medication/psychosocial treatment adherence.
      Researchers confirmed demographics through a chart review and treatment adherence
      from participants' clinicians. Multiple regression analyses examined the
      relationship between self-stigma and outcome variables. RESULTS: Mental illness
      self-stigma, racial self-concept, and to a lesser extent criminality self-stigma
      were associated with reduced self-esteem (p <= .05) and medication adherence (p
      <= .05). Criminality self-stigma also appeared to magnify the effects of racial
      and mental illness self-stigma on outcomes. CONCLUSIONS AND IMPLICATIONS: This
      study shows that self-stigma related to involvement in the criminal justice
      system may further contribute to the impact of mental illness self-stigma on
      important outcomes. Future research and interventions may tailor self-stigma
      interventions to a forensic psychiatric population.

PMID- 25938622
TI  - Why don't more patients receive intravenous rt-PA for acute stroke?
AB  - Intravenous rt-PA was proven safe and effective for acute ischemic stroke in
      1995, approved by US FDA in 1996, and endorsed by the American Heart Association,
      American Academy of Neurology, and National Stroke Association in 1997. The
      treatment is remarkably cost-effective, despite the high cost of the drug itself
      and the stroke teams to give it. Community-based practicing neurologists can use
      t-PA for acute stroke without the need for specialized expertise. The benefit is
      durable over long-term follow-up and no particular subgroups, such as the elderly
      or those with very large strokes, should be excluded from treatment. Several
      additional studies have now confirmed the beneficial effects of thrombolytic
      therapy for stroke in de novo samples. So why isn't the drug used more? Some
      troubling mis-understandings in the literature seem persistent and influential
      among clinicians. Considerable data supports the use of rt-PA for acute ischemic
      stroke, which should remove remaining doubts. 

PMID- 25938623
TI  - Synchronization of Caulobacter crescentus for investigation of the bacterial cell
      cycle.
AB  - The cell cycle is important for growth, genome replication, and development in
      all cells. In bacteria, studies of the cell cycle have focused largely on
      unsynchronized cells making it difficult to order the temporal events required
      for cell cycle progression, genome replication, and division. Caulobacter
      crescentus provides an excellent model system for the bacterial cell cycle
      whereby cells can be rapidly synchronized in a G0 state by density
      centrifugation. Cell cycle synchronization experiments have been used to
      establish the molecular events governing chromosome replication and segregation,
      to map a genetic regulatory network controlling cell cycle progression, and to
      identify the establishment of polar signaling complexes required for asymmetric
      cell division. Here we provide a detailed protocol for the rapid synchronization
      of Caulobacter NA1000 cells. Synchronization can be performed in a large-scale
      format for gene expression profiling and western blot assays, as well as a small
      scale format for microscopy or FACS assays. The rapid synchronizability and high
      cell yields of Caulobacter make this organism a powerful model system for studies
      of the bacterial cell cycle. 

PMID- 25938624
TI  - Non-invasive Imaging of the Innate Immune Response in a Zebrafish Larval Model of
      Streptococcus iniae Infection.
AB  - The aquatic pathogen, Streptococcus iniae, is responsible for over 100 million
      dollars in annual losses for the aquaculture industry and is capable of causing
      systemic disease in both fish and humans. A better understanding of S. iniae
      disease pathogenesis requires an appropriate model system. The genetic
      tractability and the optical transparency of the early developmental stages of
      zebrafish allow for the generation and non-invasive imaging of transgenic lines
      with fluorescently tagged immune cells. The adaptive immune system is not fully
      functional until several weeks post fertilization, but zebrafish larvae have a
      conserved vertebrate innate immune system with both neutrophils and macrophages.
      Thus, the generation of a larval infection model allows the study of the specific
      contribution of innate immunity in controlling S. iniae infection. The site of
      microinjection will determine whether an infection is systemic or initially
      localized. Here, we present our protocols for otic vesicle injection of zebrafish
      aged 2-3 days post fertilization as well as our techniques for fluorescent
      confocal imaging of infection. A localized infection site allows observation of
      initial microbe invasion, recruitment of host cells and dissemination of
      infection. Our findings using the zebrafish larval model of S. iniae infection
      indicate that zebrafish can be used to examine the differing contributions of
      host neutrophils and macrophages in localized bacterial infections. In addition,
      we describe how photolabeling of immune cells can be used to track individual
      host cell fate during the course of infection. 

PMID- 25938625
TI  - Molecular-Resolution Interrogation of a Porphyrin Monolayer by Ultrahigh Vacuum
      Tip-Enhanced Raman and Fluorescence Spectroscopy.
AB  - Tip-enhanced Raman scattering (TERS) and optically excited tip-enhanced
      fluorescence (TEF) of a self-assembled porphyrin monolayer on Ag(111) are studied
      using an ultrahigh vacuum scanning tunneling microscope (UHV-STM). Through
      selectively exciting different Q-bands of meso-tetrakis- (3,5
      ditertiarybutylphenyl)-porphyrin (H2TBPP), chemical information regarding
      different vibronic excited states is revealed by a combination of theory and
      experiment; namely, TERS and time-dependent density functional theory (TDDFT)
      simulations. The observed TEF spectra suggest a weak coupling of H2TBPP to the
      substrate due to the bulky t-butyl groups and a possible alternative excited
      state decay path. This work demonstrates the potential of combining TERS and TEF
      for studying surface-mounted porphyins on substrates, thus providing insight into
      porphyrin-sensitized solar cells and catalysis. 

PMID- 25938626
TI  - Microangiopathy triggers, and inducible nitric oxide synthase exacerbates dextran
      sulfate sodium-induced colitis.
AB  - Ulcerative colitis (UC) is a representative clinical manifestation of
      inflammatory bowel disease that causes chronic gastrointestinal tract
      inflammation. Dextran sulfate sodium (DSS)-induced colitis mice have been used to
      investigate UC pathogenesis, and in this UC model, disturbance and impairment of
      the mucosal epithelium have been reported to cause colitis. However, how DSS
      sporadically breaks down the epithelium remains unclear. In this study, we
      focused on the colonic microcirculation and myenteric neurons of DSS-induced
      colitis. Moreover, we examined the potential of myenteric neurons as a target to
      prevent exacerbation of colitis. Fluorescent angiographic and histopathological
      studies revealed that DSS administration elicited blood vessel disruption before
      epithelial disorders appeared. Ischemic conditions in the lamina propria induced
      inducible nitric oxide synthase (iNOS) expression in myenteric neurons as colitis
      aggravated. When neuronal activity was inhibited with butylscopolamine, neuronal
      iNOS expression decreased, and the exacerbation of colitis was prevented. These
      results suggested that DSS-induced colitis was triggered by microcirculatory
      disturbance in the mucosa, and that excessive neuronal excitation aggravated
      colitis. During remission periods of human UC, endoscopic inspection of the
      colonic microcirculation may enable the early detection of disease recurrence,
      and inhibition of neuronal iNOS expression may prevent the disease from
      worsening. 

PMID- 25938627
TI  - Curcumin regulates cell fate and metabolism by inhibiting hedgehog signaling in
      hepatic stellate cells.
AB  - Accumulating evidence indicates that Hedgehog (Hh) signaling becomes activated in
      chronic liver injury and plays a role in the pathogenesis of hepatic fibrosis.
      Hepatic stellate cells (HSCs) are Hh-responsive cells and activation of the Hh
      pathway promotes transdifferentiation of HSCs into myofibroblasts. Targeting Hh
      signaling may be a novel therapeutic strategy for treatment of liver fibrosis. We
      previously reported that curcumin has potent antifibrotic effects in vivo and in
      vitro, but the underlying mechanisms are not fully elucidated. This study shows
      that curcumin downregulated Patched and Smoothened, two key elements in Hh
      signaling, but restored Hhip expression in rat liver with carbon tetrachloride
      induced fibrosis and in cultured HSCs. Curcumin also halted the nuclear
      translocation, DNA binding, and transcription activity of Gli1. Moreover, the Hh
      signaling inhibitor cyclopamine, like curcumin, arrested the cell cycle, induced
      mitochondrial apoptosis, reduced fibrotic gene expression, restored lipid
      accumulation, and inhibited invasion and migration in HSCs. However, curcumin's
      effects on cell fate and fibrogenic properties of HSCs were abolished by the Hh
      pathway agonist SAG. Furthermore, curcumin and cyclopamine decreased
      intracellular levels of adenosine triphosphate and lactate, and inhibited the
      expression and/or function of several key molecules controlling glycolysis.
      However, SAG abrogated the curcumin effects on these parameters of glycolysis.
      Animal data also showed that curcumin downregulated glycolysis-regulatory
      proteins in rat fibrotic liver. These aggregated data therefore indicate that
      curcumin modulated cell fate and metabolism by disrupting the Hh pathway in HSCs,
      providing novel molecular insights into curcumin reduction of HSC activation. 

PMID- 25938628
TI  - Willpower versus "skillpower": Examining how self-efficacy works in treatment for
      marijuana dependence.
AB  - Self-efficacy has repeatedly been demonstrated to be a robust predictor of
      outcomes in the treatment of marijuana use disorders. It is not clear, however,
      how increases in confidence in ability to refrain from use get translated into
      actual improvements in drug-related outcomes. Marlatt, among others, viewed the
      acquisition and use of coping skills as the key to behavior change, and self
      efficacy as a cognitive state that enabled coping. But that model of behavior
      change has not been supported, and few studies have shown that the effects of
      self-efficacy are mediated by coping or by other processes. The current study
      combined 3 marijuana treatment trials comprising 901 patients to examine the
      relationships between self-efficacy, coping, and potential mediators, to
      determine if the effects of self-efficacy on outcomes could be explained. Results
      of multilevel models indicated that self-efficacy was a strong predictor of
      adaptive outcomes in all trials, even when no active treatment was provided.
      Tests of mediation showed that effects of self-efficacy on marijuana use and on
      marijuana-related problems were partially mediated by use of coping skills and by
      reductions in emotional distress, but that direct effects of self-efficacy
      remained largely unexplained. The results are seen as supportive of efforts to
      improve coping skills and reduce distress in marijuana treatment, but also
      suggest that additional research is required to discover what is actually
      occurring when substance use changes, and how self-efficacy enables those
      changes.

PMID- 25938629
TI  - Computer-assisted behavioral therapy and contingency management for cannabis use
      disorder.
AB  - Computer-assisted behavioral treatments hold promise for enhancing access to and
      reducing costs of treatments for substance use disorders. This study assessed the
      efficacy of a computer-assisted version of an efficacious, multicomponent
      treatment for cannabis use disorders (CUD), that is, motivational enhancement
      therapy, cognitive-behavioral therapy, and abstinence-based contingency
      management (MET/CBT/CM). An initial cost comparison was also performed. Seventy
      five adult participants, 59% Black, seeking treatment for CUD received either,
      MET only (BRIEF), therapist-delivered MET/CBT/CM (THERAPIST), or computer
      delivered MET/CBT/CM (COMPUTER). During treatment, the THERAPIST and COMPUTER
      conditions engendered longer durations of continuous cannabis abstinence than
      BRIEF (p < .05), but did not differ from each other. Abstinence rates and
      reduction in days of use over time were maintained in COMPUTER at least as well
      as in THERAPIST. COMPUTER averaged approximately $130 (p < .05) less per case
      than THERAPIST in therapist costs, which offset most of the costs of CM. Results
      add to promising findings that illustrate potential for computer-assisted
      delivery methods to enhance access to evidence-based care, reduce costs, and
      possibly improve outcomes. The observed maintenance effects and the cost findings
      require replication in larger clinical trials.

PMID- 25938630
TI  - Online gaming in the context of social anxiety.
AB  - In 2014, over 23 million individuals were playing massive multiplayer online role
      playing games (MMORPGs). In light of the framework provided by Davis's (2001)
      cognitive-behavioral model of pathological Internet use, social anxiety,
      expressions of true self, and perceived in-game and face-to-face social support
      were examined as predictors of Generalized Problematic Internet Use Scale (GPIUS)
      scores and hours spent playing MMORPGs per week. Data were collected from adult
      MMORPG players via an online survey (N = 626). Using structural equation
      modeling, the hypothesized model was tested on 1 half of the sample (N = 313) and
      then retested on the other half of the sample. The results indicated that the
      hypothesized model fit the data well in both samples. Specifically, expressing
      true self in game, higher levels of social anxiety, larger numbers of in-game
      social supports, and fewer supportive face-to-face relationships were significant
      predictors of higher GPIUS scores, and the number of in-game supports was
      significantly associated with time spent playing. The current study provides
      clinicians and researchers with a deeper understanding of MMORPG use by being the
      first to apply, test, and replicate a theory-driven model across 2 samples of
      MMORPG players. In addition, the present findings suggest that a psychometric
      measure of MMORPG usage is more indicative of players' psychological and social
      well-being than is time spent playing these games. (PsycINFO Database Record 

PMID- 25938632
TI  - Elevated Lipoprotein(a) Does Not Cause Low-Grade Inflammation Despite Causal
      Association With Aortic Valve Stenosis and Myocardial Infarction: A Study of
      100,578 Individuals from the General Population.
AB  - CONTEXT: It is unknown whether elevated lipoprotein(a) is causally associated
      with low-grade inflammation. OBJECTIVE: We tested the hypothesis that elevated
      lipoprotein(a) is observationally and causally associated with low-grade
      inflammation together with aortic valve stenosis and myocardial infarction.
      DESIGN AND SETTING: Using a multidirectional Mendelian randomization approach, we
      studied 100,578 individuals from the Danish general population with plasma levels
      of and/or genotypes known to affect levels of lipoprotein(a) and C-reactive
      protein (CRP), and using information regarding diagnosis of aortic valve stenosis
      and of myocardial infarction (MI) from registries. RESULTS: Observationally, CRP
      increased by 29% (95% confidence interval [CI], 23-34) per 50-mg/dL increase in
      lipoprotein(a). However, two LPA single nucleotide polymorphisms (SNPs) and the
      kringle IV type 2 (KIV-2) genotype that were associated with 98, 95, and 68 mg/dL
      higher lipoprotein(a) levels were not causally associated with increased CRP
      levels. For aortic valve stenosis, a 1-SD increase in lipoprotein(a) levels was
      associated observationally with a multifactorially adjusted hazard ratio of 1.23
      (95% CI, 1.06-1.41), with corresponding causal risk ratios of 1.38 (1.23-1.55)
      based on LPA SNPs and of 1.21 (1.06-1.40) based on LPA KIV-2 genotype. For
      myocardial infarction, corresponding values were 1.20 (1.10;1.31)
      observationally, and 1.18 (1.11;1.26) and 1.31 (1.22;1.42) causally,
      respectively. Observational hazard ratios for aortic valve stenosis and MI were
      similar after further adjustment for CRP levels. CONCLUSIONS: Elevated levels of
      lipoprotein(a) were not causally associated with increased low-grade inflammation
      as measured through CRP despite a causal association with increased risk of
      aortic valve stenosis and MI.

PMID- 25938631
TI  - Prevalence and correlates of sipping alcohol in a prospective middle school
      sample.
AB  - Research documents an association between early use of alcohol and adverse
      outcomes. Most studies on drinking initiation exclude sipping or confound sips
      with consumption of a full drink. However, even a few sips of alcohol can
      constitute a meaningful experience for naive drinkers. Prior research with this
      project indicated that sipping before middle school predicted subsequent adverse
      outcomes (at high-school entry), even controlling for child externalizing and
      sensation seeking and parent alcohol use. The present study extends our prior
      work by examining the correlates of early sipping and sipping onset. The sample
      was comprised of 1,023 6th, 7th, and 8th graders (52% female; 24% non-White, and
      12% Hispanic). Participants completed Web-based surveys on 5 occasions over the
      course of 2 years. The prevalence of sipping at Wave 1 was 37%, with 29% of never
      sippers initiating sipping within 2 years. Sipping was associated with stronger
      alcohol-related cognitions and low school engagement as well as contextual
      influences in the peer, sibling, and parent domains. Sipping onset among never
      sippers was prospectively predicted by sensation seeking and problem behavior as
      well as parental and sibling influences. More important, mere availability of
      alcohol was a strong correlate both concurrently and prospectively. Further
      analyses demonstrated that youth who sipped alcohol with parental permission had
      a lower profile of risk and healthier relationships with parents as compared with
      youth who reported unsanctioned sipping. Findings point to the importance of
      considering fine-grained early drinking behavior and call for further attention
      to sipping in research on initiation of alcohol use.

PMID- 25938634
TI  - Dietary Exposure to Individual Polybrominated Diphenyl Ether Congeners BDE-47 and
      BDE-99 Alters Innate Immunity and Disease Susceptibility in Juvenile Chinook
      Salmon.
AB  - Polybrominated diphenyl ethers (PBDEs), used as commercial flame-retardants, are
      bioaccumulating in threatened Pacific salmon. However, little is known of PBDE
      effects on critical physiological functions required for optimal health and
      survival. BDE-47 and BDE-99 are the predominant PBDE congeners found in Chinook
      salmon collected from the Pacific Northwest. In the present study, both innate
      immunity (phagocytosis and production of superoxide anion) and pathogen challenge
      were used to evaluate health and survival in groups of juvenile Chinook salmon
      exposed orally to either BDE-47 or BDE-99 at environmentally relevant
      concentrations. Head kidney macrophages from Chinook salmon exposed to BDE-99,
      but not those exposed to BDE-47, were found to have a reduced ability in vitro to
      engulf foreign particles. However, both congeners increased the in vitro
      production of superoxide anion in head kidney macrophages. Salmon exposed to
      either congener had reduced survival during challenge with the pathogenic marine
      bacteria Listonella anguillarum. The concentration response curves generated for
      these end points were nonmonotonic and demonstrated a requirement for using
      multiple environmentally relevant PBDE concentrations for effect studies.
      Consequently, predicting risk from toxicity reference values traditionally
      generated with monotonic concentration responses may underestimate PBDE effect on
      critical physiological functions required for optimal health and survival in
      salmon. 

PMID- 25938633
TI  - Sitagliptin Reduces Inflammation and Chronic Immune Cell Activation in HIV+
      Adults With Impaired Glucose Tolerance.
AB  - CONTEXT: HIV infection is associated with a greater risk for fasting
      hyperinsulinemia, impaired glucose tolerance, and higher incidence rates for
      vascular disease, myocardial infarction, or stroke despite effective combination
      antiretroviral therapy (cART). The underlying mechanism(s) may involve chronic
      low-grade systemic inflammation and immune cell activation. Dipeptidyl peptidase
      4 inhibitors (sitagliptin) improve glucose tolerance and may possess
      immunomodulatory effects because leukocyte CD26 cell surface receptors express
      dipeptidyl peptidase-4 activity. OBJECTIVE: Sitagliptin will reduce inflammatory
      and immune cell activation markers known to be elevated in cART-treated HIV
      infected (HIV+) adults with impaired glucose tolerance. DESIGN: This was designed
      as a prospective, randomized, placebo-controlled, double-blind trial of
      sitagliptin in HIV+ adults. SETTING: The setting was an academic medical center.
      PATIENTS: Patients were cART-treated HIV+ men and women (n = 36) with stable HIV
      disease and impaired glucose tolerance. INTERVENTIONS: Interventions included
      sitagliptin 100 mg/d or placebo for 8 weeks. MAIN OUTCOME MEASURES: At baseline
      and week 8, plasma high-sensitivity C-reactive protein and C-X-C motif chemokine
      10 concentrations (ELISA), oral glucose tolerance, and abdominal sc adipose mRNA
      expression for M1 macrophage markers (monocyte chemotactic protein-1, EGF-like
      module-containing, mucin-like hormone receptor 1). RESULTS: Sitagliptin reduced
      glucose area under the curve (P = .002) and improved oral glucose insulin
      sensitivity index (P = .04) more than placebo. Sitagliptin reduced plasma high
      sensitivity C-reactive protein and C-X-C motif chemokine 10 levels more than
      placebo (P < .009). Adipose tissue monocyte chemotactic protein-1 mRNA abundance
      declined significantly more (P = .01), and adipose EGF-like module-containing,
      mucin-like hormone receptor 1 mRNA expression tended to decline more (P = .19) in
      sitagliptin than placebo. CONCLUSION: Sitagliptin had beneficial systemic and
      adipose anti-inflammatory effects in cART-treated HIV+ adults with impaired
      glucose tolerance. Large-scale, long-term studies should determine whether
      sitagliptin reduces cardiovascular risk and events in HIV+ adults.

PMID- 25938635
TI  - Efficient and selective removal of dyes using imidazolium-based supramolecular
      gels.
AB  - A supramolecular gel was constructed by using an imidazolium-based surfactant, N
      cetyl-N'-carboxymethyl imidazolium bromide ([N-C16, N'-CO2H-Im]Br), in the
      DMSO/H2O binary solvent mixtures and investigated as an adsorbent for removing
      dyes from aqueous solution. The self-assembled gel displays a morphology of
      microplatelets stacked in bilayer units with interdigitated hydrocarbon tails,
      and the structure remains unchanged below the sol-gel transition temperature. The
      gel also exhibits a strong birefringence property and excellent mechanical
      strength. In particular, the gels show superior performance in removal of anionic
      dye molecules, for example, removing 80% of eosin Y within 10 min, The
      constructed gels also present excellent salinity tolerance, even when the
      concentration of NaCl is 1000 times higher than that of the dye, and can maintain
      their high efficiency after 25 cycles, indicative of their promise in water
      treatment. 

PMID- 25938636
TI  - Automated quantification of hematopoietic cell - stromal cell interactions in
      histological images of undecalcified bone.
AB  - Confocal microscopy is the method of choice for the analysis of localization of
      multiple cell types within complex tissues such as the bone marrow. However, the
      analysis and quantification of cellular localization is difficult, as in many
      cases it relies on manual counting, thus bearing the risk of introducing a rater
      dependent bias and reducing interrater reliability. Moreover, it is often
      difficult to judge whether the co-localization between two cells results from
      random positioning, especially when cell types differ strongly in the frequency
      of their occurrence. Here, a method for unbiased quantification of cellular co
      localization in the bone marrow is introduced. The protocol describes the sample
      preparation used to obtain histological sections of whole murine long bones
      including the bone marrow, as well as the staining protocol and the acquisition
      of high-resolution images. An analysis workflow spanning from the recognition of
      hematopoietic and non-hematopoietic cell types in 2-dimensional (2D) bone marrow
      images to the quantification of the direct contacts between those cells is
      presented. This also includes a neighborhood analysis, to obtain information
      about the cellular microenvironment surrounding a certain cell type. In order to
      evaluate whether co-localization of two cell types is the mere result of random
      cell positioning or reflects preferential associations between the cells, a
      simulation tool which is suitable for testing this hypothesis in the case of
      hematopoietic as well as stromal cells, is used. This approach is not limited to
      the bone marrow, and can be extended to other tissues to permit reproducible,
      quantitative analysis of histological data. 

PMID- 25938637
TI  - Is single-4-ring the most basic but elusive secondary building unit that
      transforms to larger structures in zinc phosphate chemistry?
AB  - Haloaryl phosphates (X-dippH2, X = Cl, Br, I) react with zinc acetate in the
      presence of collidine or 2-aminopyridine (2-apy) to yield zinc phosphate clusters
      [Zn(X-dipp)(collidine)]4 (X = Cl (1), Br (2), I (3)) and [Zn(X-dipp)(2
      apy)]4.2MeOH (X = Cl (4), Br (5), I (6)), respectively. Single-crystal X-ray
      diffraction studies reveal that collidine and 2-apy capped zinc phosphates 1-6
      exist as discrete tetrameric zinc phosphate molecules, exhibiting a cubane-shaped
      D4R core. In contrast, when the same reaction has been carried out in the
      presence of 4-cyanopyridine (4-CNpy), polymeric zinc phosphates {[Zn4(X-dipp)4(4
      CNpy)2(MeOH)2].2H2O}n (X = Cl (7), Br (8), I (9)) have been isolated. Compounds 7
      9 are square-wave-shaped, one-dimensional polymers composed of fused S4R
      repeating units. The common structural motif found both in D4R cubanes 1-6 and
      polymers 7-9 is the S4R building block, which presumably undergoes further fusion
      because of the coordinative unsaturation at zinc and the simultaneous presence of
      free P?O. The closed shell cubanes 1-6 are obviously formed by a face-to-face
      dimerization involving two S4R units in which the two P?O groups are in cis
      configuration. On the other hand, the one-dimensional (1-D) square-wave polymers
      7-9 are formed from a face-to-face association of S4R building units in which the
      two P?O groups are in a trans-configuration. In order to stabilize these elusive
      S4R zinc phosphates, the reaction between Cl-dippH2 and zinc acetate was carried
      out in the presence of excess imidazole as an ancillary ligand (1:1:4), although
      only an imidazole decorated cubane cluster [Zn(Cl-dipp)(imz)]4.2MeOH (10) was
      isolated. The chelating N,N'-donor 1,10-phenanthroline ligand was used to
      eventually isolate cyclic S4R phosphate [Zn(MU2-Cl-dipp)(1,10
      phen)(OH2)]2.MeOH.H2O (11). The change of Zn(2+) source to zinc nitrate and the
      phosphate source to 2,6-dimethylphenyl phosphate (dmppH2) led to the isolation of
      another polymeric phosphate [Zn(dmpp)(MeOH)]n (12), with a zigzag backbone,
      formed through an edge-to-edge to polymerization of S4R building units with P?O
      groups in trans-configuration. The isolation of four different structural types
      of zinc phosphates A-D in the present study can be rationalized in terms of
      fusion of S4R rings in a variety of ways to either produce discrete clusters or 1
      D polymers. 

PMID- 25938639
TI  - Producing Isotopic Distribution Models for Fully Apodized Absorption Mode FT-MS.
AB  - Isotopic distributions are frequently used as part of the peak assignment process
      in the processing of mass spectra. The best methods for producing accurate peak
      assignments must account for the peak shape and resolving power. In other words,
      the full profile of the isotopic distribution is important. Conventional methods
      for modeling isotopic distributions generally assume a peak profile that is not
      applicable to fully apodized absorption mode spectra because the peak shapes in
      these spectra are distinctly different from those seen in normal (i.e., magnitude
      mode) spectra. We present results illustrating this problem and describe a method
      for producing more accurate isotopic distribution models for this class of
      spectra. 

PMID- 25938638
TI  - Long-term effect of gene therapy on Leber's congenital amaurosis.
AB  - BACKGROUND: Mutations in RPE65 cause Leber's congenital amaurosis, a progressive
      retinal degenerative disease that severely impairs sight in children. Gene
      therapy can result in modest improvements in night vision, but knowledge of its
      efficacy in humans is limited. METHODS: We performed a phase 1-2 open-label trial
      involving 12 participants to evaluate the safety and efficacy of gene therapy
      with a recombinant adeno-associated virus 2/2 (rAAV2/2) vector carrying the RPE65
      complementary DNA, and measured visual function over the course of 3 years. Four
      participants were administered a lower dose of the vector, and 8 were
      administered a higher dose. In a parallel study in dogs, we investigated the
      relationship among vector dose, visual function, and electroretinography (ERG)
      findings. RESULTS: Improvements in retinal sensitivity were evident, to varying
      extents, in six participants for up to 3 years, peaking at 6 to 12 months after
      treatment and then declining. No associated improvement in retinal function was
      detected by means of ERG. Three participants had intraocular inflammation, and
      two had clinically significant deterioration of visual acuity. The reduction in
      central retinal thickness varied among participants. In dogs, RPE65 gene therapy
      with the same vector at lower doses improved vision-guided behavior, but only
      higher doses resulted in improvements in retinal function that were detectable
      with the use of ERG. CONCLUSIONS: Gene therapy with rAAV2/2 RPE65 vector improved
      retinal sensitivity, albeit modestly and temporarily. Comparison with the results
      obtained in the dog model indicates that there is a species difference in the
      amount of RPE65 required to drive the visual cycle and that the demand for RPE65
      in affected persons was not met to the extent required for a durable, robust
      effect. (Funded by the National Institute for Health Research and others;
      ClinicalTrials.gov number, NCT00643747.).

PMID- 25938640
TI  - Structure and conformation of protonated D-(+)-biotin in the unsolvated state.
AB  - A combined computational and infrared multiphoton dissociation (IRMPD)
      spectroscopic investigation shows that protonated d-(+)-biotin, formed in the gas
      phase by ESI-MS, acquires a folded structure with proton bonding between the
      ureido and valeryl carbonyls, and that only a single conformer of such a
      structure predominates. A uniform frequency vs distance correlation function is
      proposed for the O(+)-H...O and N-H...O bonds involved in the folded conformers
      of O2'-protonated d-(+)-biotin in the gas phase which, therefore, depends
      exclusively on the corresponding geometric parameters. 

PMID- 25938641
TI  - Large-scale evaluation of maize germplasm for low-phosphorus tolerance.
AB  - Low-phosphorus (LP) stress is a global problem for maize production and has been
      exacerbated by breeding activities that have reduced the genetic diversity of
      maize. Although LP tolerance in maize has been previously evaluated, the
      evaluations were generally performed with only a small number of accessions or
      with samples collected from a limited area. In this research, 826 maize
      accessions (including 580 tropical/subtropical accessions and 246 temperate
      accessions) were evaluated for LP tolerance under field conditions in 2011 and
      2012. Plant height (PH) and leaf number were measured at three growth stages. The
      normalized difference vegetation index (NDVI) and fresh ear weight (FEW) were
      also measured. Genetic correlation analysis revealed that FEW and NDVI were
      strongly correlated with PH, especially at later stages. LP-tolerant and 
      sensitive accessions were selected based on the relative trait values of all
      traits using principal component analysis, and all the 14 traits of the tolerant
      maize accessions showed less reduction than the sensitive accessions under LP
      conditions. LP tolerance was strongly correlated with agronomic performance under
      LP stress conditions, and both criteria could be used for genetic analysis and
      breeding of LP tolerance. Temperate accessions showed slightly better LP
      tolerance than tropical/subtropical ones, although more tolerant accessions were
      identified from tropical/subtropical accessions, which could be contributed by
      their larger sample size. This large-scale evaluation provides useful
      information, LP-tolerant germplasm resources and evaluation protocol for genetic
      analysis and developing maize varieties for LP tolerance. 

PMID- 25938642
TI  - Rapid biodegradation of organophosphorus pesticides by Stenotrophomonas sp. G1.
AB  - Organophosphorus insecticides have been widely used, which are highly poisonous
      and cause serious concerns over food safety and environmental pollution. A
      bacterial strain being capable of degrading O,O-dialkyl phosphorothioate and O,O
      dialkyl phosphate insecticides, designated as G1, was isolated from sludge
      collected at the drain outlet of a chlorpyrifos manufacture plant. Physiological
      and biochemical characteristics and 16S rDNA gene sequence analysis suggested
      that strain G1 belongs to the genus Stenotrophomonas. At an initial concentration
      of 50 mg/L, strain G1 degraded 100% of methyl parathion, methyl paraoxon,
      diazinon, and phoxim, 95% of parathion, 63% of chlorpyrifos, 38% of profenofos,
      and 34% of triazophos in 24 h. Orthogonal experiments showed that the optimum
      conditions were an inoculum volume of 20% (v/v), a substrate concentration of 50
      mg/L, and an incubation temperature in 40  degrees C. p-Nitrophenol was detected
      as the metabolite of methyl parathion, for which intracellular methyl parathion
      hydrolase was responsible. Strain G1 can efficiently degrade eight
      organophosphorus pesticides (OPs) and is a very excellent candidate for
      applications in OP pollution remediation.

PMID- 25938643
TI  - Sorption/desorption behavior of triclosan in sediment-water-rhamnolipid systems:
      Effects of pH, ionic strength, and DOM.
AB  - Effects of pH, ionic strength and DOM on the sorption and desorption of triclosan
      (TCS) in sediment-water-rhamnolipid systems were systematically investigated
      through controlled batch experiments. Results showed that solubilization
      enhancement of TCS by rhamnolipid was higher in acid pH range than in alkaline pH
      range and was the highest at the ionic strength of 5*10(-2) M. Sorption of
      rhamnolipid onto sediment decreased with the increase of pH while the result was
      contrary to ionic strength. Moreover, the apparent distribution coefficients of
      TCS (Kd(*)) decreased from 73.35 to 32.30 L/kg with an increase of solution pH,
      as varying pH had significant influence on sorption of RL onto sediment and
      degree of ionization of TCS. Rhamnolipid presented the largest distribution
      capacity of TCS into the aqueous phase at moderate ionic strength (5*10(-2) M)
      with the Kd(*) of 17.26 L/kg. Further results also indicated that the presence of
      humic acid in aqueous phase could increase the desorption of TCS from
      contaminated sediment. The desorption enhancement was much higher in the system
      containing both rhamnolipid and DOM than in the single system. These findings
      provide meaningful information for enhanced migration of TCS from sediment to
      water by rhamnolipid.

PMID- 25938647
TI  - Follicular rash on the knees and hyperkeratotic palms: a difficult diagnosis.

PMID- 25938644
TI  - A Modified In vitro Invasion Assay to Determine the Potential Role of Hormones,
      Cytokines and/or Growth Factors in Mediating Cancer Cell Invasion.
AB  - Blood serum serves as a chemoattractant towards which cancer cells migrate and
      invade, facilitating their intravasation into microvessels. However, the actual
      molecules towards which the cells migrate remain elusive. This modified invasion
      assay has been developed to identify targets which drive cell migration and
      invasion. This technique compares the invasion index under three conditions to
      determine whether a specific hormone, growth factor, or cytokine plays a role in
      mediating the invasive potential of a cancer cell. These conditions include i)
      normal fetal bovine serum (FBS), ii) charcoal-stripped FBS (CS-FBS), which
      removes hormones, growth factors, and cytokines and iii) CS-FBS + molecule
      (denoted "X"). A significant change in cell invasion with CS-FBS as compared to
      FBS, indicates the involvement of hormones, cytokines or growth factors in
      mediating the change. Individual molecules can then be added back to CS-FBS to
      assay their ability to reverse or rescue the invasion phenotype. Furthermore, two
      or more factors can be combined to evaluate the additive or synergistic effects
      of multiple molecules in driving or inhibiting invasion. Overall, this method
      enables the investigator to determine whether hormones, cytokines, and/or growth
      factors play a role in cell invasion by serving as chemoattractants or inhibitors
      of invasion for a particular type of cancer cell or a specific mutant. By
      identifying specific chemoattractants and inhibitors, this modified invasion
      assay may help to elucidate signaling pathways that direct cancer cell invasion. 

PMID- 25938648
TI  - Placebo effects in infants, toddlers, and parents.

PMID- 25938649
TI  - Placebo effects in infants, toddlers, and parents.

PMID- 25938650
TI  - Placebo effects in infants, toddlers, and parents--reply.

PMID- 25938651
TI  - Folic acid supplements during pregnancy in specific clinical settings: what do we
      know about epilepsy?

PMID- 25938653
TI  - Error in web-only supplement.

PMID- 25938652
TI  - Folic acid supplements during pregnancy in specific clinical settings--reply:
      what do we know about epilepsy?

PMID- 25938654
TI  - Page for patients. The misuse of prescription pain medicine among children and
      teens.

PMID- 25938655
TI  - Behavioral and nutritional treatment for preschool-aged children with cystic
      fibrosis: a randomized clinical trial.
AB  - IMPORTANCE: Evidence-based treatments that achieve optimal energy intake and
      improve growth in preschool-aged children with cystic fibrosis (CF) are a
      critical need. OBJECTIVE: To test whether behavioral and nutritional treatment
      (intervention) was superior to an education and attention control treatment in
      increasing energy intake, weight z (WAZ) score, and height z (HAZ) score. DESIGN,
      SETTING, AND PARTICIPANTS: This randomized clinical trial included 78 children
      aged 2 to 6 years (mean age, 3.8 years) with CF and pancreatic insufficiency
      (intervention, n = 36 and control, n = 42). The study was conducted at 7 CF
      centers between January 2006 and November 2012; all 78 participants who met
      intent-to-treat criteria completed through follow-up. INTERVENTIONS: Behavioral
      intervention combined individualized nutritional counseling targeting increased
      energy intake and training in behavioral child management skills. The control arm
      provided education and served as a behavioral placebo controlling for attention
      and contact frequency. Both treatments were delivered in person or telehealth
      (via telephone). Sessions occurred weekly for 8 weeks then monthly for 4 months
      (6 months). Participants then returned to standard care for 1 year, with 12-month
      follow-up thereafter. MAIN OUTCOMES AND MEASURES: Changes in energy intake and
      WAZ score were examined from pretreatment to posttreatment (6 months) and change
      in HAZ score was assessed pretreatment to follow-up (18 months). Covariates
      included sex, Pseudomonas aeruginosa status at baseline, and treatment modality
      (in person vs telehealth). RESULTS: At baseline, mean (SD) energy intake was 1462
      (329) kcals/d, WAZ score was -0.44 (0.81), and HAZ score was -0.55 (0.84). From
      pretreatment to posttreatment, the intervention increased daily energy intake by
      485 calories vs 58 calories for the control group (adjusted difference, 431
      calories; 95% CI, 282 to 581; P < .001) and increased the WAZ score by 0.12 units
      vs 0.06 for the control (adjusted difference, 0.09; 95% CI, -0.06 to 0.24; P =
      .25). From pretreatment to follow-up, the intervention increased the HAZ score by
      0.09 units vs -0.02 for the control (adjusted difference, 0.14 units; 95% CI,
      0.001 to 0.27; P = .049). Measured treatment integrity and credibility were high
      for both groups. CONCLUSIONS AND RELEVANCE: Behavioral and nutritional
      intervention improved energy intake and HAZ score outcomes but not WAZ score
      outcomes. Our results provide evidence that behavioral and nutritional treatment
      may be efficacious as a nutritional intervention for preschoolers aged 2 to 6
      years with CF and pancreatic insufficiency. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier:NCT00241969.

PMID- 25938656
TI  - Optimizing nutritional health through behavioral intervention in young children
      with cystic fibrosis.

PMID- 25938657
TI  - Association between competitive food and beverage policies in elementary schools
      and childhood overweight/obesity trends: differences by neighborhood
      socioeconomic resources.
AB  - IMPORTANCE: To our knowledge, few published studies have examined the influence
      of competitive food and beverage (CF&B) policies on student weight outcomes; none
      have investigated disparities in the influence of CF&B policies on children's
      body weight by school neighborhood socioeconomic resources. OBJECTIVE: To
      investigate whether the association between CF&B policies and population-level
      trends in childhood overweight/obesity differed by school neighborhood income and
      education levels. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study,
      from July 2013 to October 2014, compared overweight/obesity prevalence trends
      before (2001-2005) and after (2006-2010) implementation of CF&B policies in
      public elementary schools in California. The study included 2 700 880 fifth-grade
      students in 5362 public schools from 2001 to 2010. EXPOSURES: California CF&B
      policies (effective July 1, 2004, and July 1, 2007) and school neighborhood
      income and education levels. MAIN OUTCOMES AND MEASURES: Overweight/obesity
      defined as a body mass index at or greater than the 85th percentile for age and
      sex. RESULTS: Overall rates of overweight/obesity ranged from 43.5% in 2001 to
      45.8% in 2010. Compared with the period before the introduction of CF&B policies,
      overweight/obesity trends changed in a favorable direction after the policies
      took effect (2005-2010); these changes occurred for all children across all
      school neighborhood socioeconomic levels. In the postpolicy period, these trends
      differed by school neighborhood socioeconomic advantage. From 2005-2010, trends
      in overweight/obesity prevalence leveled off among students at schools in
      socioeconomically disadvantaged neighborhoods but declined in socioeconomically
      advantaged neighborhoods. Students in the lowest-income neighborhoods experienced
      zero or near zero change in the odds of overweight/obesity over time: the annual
      percentage change in overweight/obesity odds was 0.1% for females (95% CI, -0.7
      to 0.9) and -0.3% for males (95% CI, -1.1 to 0.5). In contrast, in the highest
      income neighborhoods, the annual percentage decline in the odds of overweight was
      1.2% for females (95% CI, 0.4 to 1.9) and 1.0% for males (95% CI, 0.3 to 1.8).
      Findings were similar for school neighborhood education. CONCLUSIONS AND
      RELEVANCE: Our study found population-level improvements in the prevalence of
      childhood overweight/obesity that coincided with the period following
      implementation of statewide CF&B policies (2005-2010). However, these
      improvements were greatest at schools in the most advantaged neighborhoods. This
      suggests that CF&B policies may help prevent child obesity; however, the degree
      of their effectiveness is likely to depend on socioeconomic and other contextual
      factors in school neighborhoods. To reduce disparities and prevent obesity,
      school policies and environmental interventions must address relevant contextual
      factors in school neighborhoods.

PMID- 25938658
TI  - Photochemical Conversion of Phenanthro[9,10-d]imidazoles into pi-Expanded
      Heterocycles.
AB  - We discovered that phenanthro[9,10-d]imidazoles bearing a 2-halogenoaryl
      substituent at position 2 undergo swift photochemically driven direct arylation,
      leading to barely known phenanthro[9',10':4,5]imidazo[1,2-f]phenanthridines. The
      reaction is high-yielding, and it does not require any sensitizer or base. The
      discovered process is tolerant of a variety of substituents present both at
      positions 1 and 2; i.e., strongly electron-donating and electron-withdrawing
      substituents are tolerated as well as various heterocyclic units. Steric
      hindrance does not affect this process. The evidence gathered here indicates that
      SRN1 mechanism is operating in this case with the formation of radical anion as a
      critical step, followed by heterolytic cleavage of a carbon-halogen bond. Also
      TfO groups were shown to undergo cyclization, which allows the use of
      salicylaldehydes in the construction of heterocyclic systems. Efficiency of this
      photochemically driven direct arylation has been demonstrated by the synthesis of
      two systems possessing 13 and 17 conjugated rings, respectively.
      Phenanthro[9',10':4,5]imidazo[1,2-f]phenanthridines are blue-emitters, and they
      exhibit strong fluorescence in solution and in the solid state in direct contrast
      to their precursors. 

PMID- 25938659
TI  - Efficacy of Enzyme and Substrate Reduction Therapy with a Novel Antagonist of
      Glucosylceramide Synthase for Fabry Disease.
AB  - Fabry disease, an X-linked glycosphingolipid storage disorder, is caused by the
      deficient activity of alpha-galactosidase A (alpha-Gal A). This results in the
      lysosomal accumulation in various cell types of its glycolipid substrates,
      including globotriaosylceramide (GL-3) and lysoglobotriaosylceramide
      (globotriaosyl lysosphingolipid, lyso-GL-3), leading to kidney, heart, and
      cerebrovascular disease. To complement and potentially augment the current
      standard of care, biweekly infusions of recombinant alpha-Gal A, the merits of
      substrate reduction therapy (SRT) by selectively inhibiting glucosylceramide
      synthase (GCS) were examined. Here, we report the development of a novel, orally
      available GCS inhibitor (Genz-682452) with pharmacological and safety profiles
      that have potential for treating Fabry disease. Treating Fabry mice with Genz
      682452 resulted in reduced tissue levels of GL-3 and lyso-GL-3 and a delayed loss
      of the thermal nociceptive response. Greatest improvements were realized when the
      therapeutic intervention was administered to younger mice before they developed
      overt pathology. Importantly, as the pharmacologic profiles of alpha-Gal A and
      Genz-682452 are different, treating animals with both drugs conferred the
      greatest efficacy. For example, because Genz-682452, but not alpha-Gal A, can
      traverse the blood-brain barrier, levels of accumulated glycosphingolipids were
      reduced in the brain of Genz-682452-treated but not alpha-Gal A-treated mice.
      These results suggest that combining substrate reduction and enzyme replacement
      may confer both complementary and additive therapeutic benefits in Fabry disease.

PMID- 25938660
TI  - Vps4 disassembles an ESCRT-III filament by global unfolding and processive
      translocation.
AB  - The AAA+ ATPase Vps4 disassembles ESCRT-III and is essential for HIV-1 budding
      and other pathways. Vps4 is a paradigmatic member of a class of hexameric AAA+
      ATPases that disassemble protein complexes without degradation. To distinguish
      between local displacement versus global unfolding mechanisms for complex
      disassembly, we carried out hydrogen/deuterium exchange during Saccharomyces
      cerevisiae Vps4 disassembly of a chimeric Vps24-2 ESCRT-III filament. EX1
      exchange behavior shows that Vps4 completely unfolds ESCRT-III substrates on a
      time scale consistent with the disassembly reaction. The established unfoldase
      ClpX showed the same pattern, thus demonstrating a common unfolding mechanism.
      Vps4 hexamers containing a single cysteine residue in the pore loops were cross
      linked to ESCRT-III subunits containing unique cysteines within the folded core
      domain. These data support a mechanism in which Vps4 disassembles its substrates
      by completely unfolding them and threading them through the central pore. 

PMID- 25938661
TI  - Repulsive guidance molecule is a structural bridge between neogenin and bone
      morphogenetic protein.
AB  - Repulsive guidance molecules (RGMs) control crucial processes including cell
      motility, adhesion, immune-cell regulation and systemic iron metabolism. RGMs
      signal via the neogenin (NEO1) and the bone morphogenetic protein (BMP) pathways.
      Here, we report crystal structures of the N-terminal domains of all human RGM
      family members in complex with the BMP ligand BMP2, revealing a new protein fold
      and a conserved BMP-binding mode. Our structural and functional data suggest a pH
      linked mechanism for RGM-activated BMP signaling and offer a rationale for RGM
      mutations causing juvenile hemochromatosis. We also determined the crystal
      structure of the ternary BMP2-RGM-NEO1 complex, which, along with solution
      scattering and live-cell super-resolution fluorescence microscopy, indicates BMP
      induced clustering of the RGM-NEO1 complex. Our results show how RGM acts as the
      central hub that links BMP and NEO1 and physically connects these fundamental
      signaling pathways. 

PMID- 25938662
TI  - Abeta(1-42) fibril structure illuminates self-recognition and replication of
      amyloid in Alzheimer's disease.
AB  - Increasing evidence has suggested that formation and propagation of misfolded
      aggregates of 42-residue human amyloid beta (Abeta(1-42)), rather than of the
      more abundant Abeta(1-40), provokes the Alzheimer's disease cascade. However,
      structural details of misfolded Abeta(1-42) have remained elusive. Here we
      present the atomic model of an Abeta(1-42) amyloid fibril, from solid-state NMR
      (ssNMR) data. It displays triple parallel-beta-sheet segments that differ from
      reported structures of Abeta(1-40) fibrils. Remarkably, Abeta(1-40) is
      incompatible with the triple-beta-motif, because seeding with Abeta(1-42) fibrils
      does not promote conversion of monomeric Abeta(1-40) into fibrils via cross
      replication. ssNMR experiments suggest that C-terminal Ala42, absent in Abeta(1
      40), forms a salt bridge with Lys28 to create a self-recognition molecular switch
      that excludes Abeta(1-40). The results provide insight into the Abeta(1-42)
      selective self-replicating amyloid-propagation machinery in early-stage
      Alzheimer's disease. 

PMID- 25938663
TI  - Depressive symptoms as a novel risk factor for recurrent venous thromboembolism:
      a longitudinal observational study in patients referred for thrombophilia
      investigation.
AB  - BACKGROUND: Increasing evidence suggests that psychosocial factors, including
      depression predict incident venous thromboembolism (VTE) against a background of
      genetic and acquired risk factors. The role of psychosocial factors for the risk
      of recurrent VTE has not previously been examined. We hypothesized that
      depressive symptoms in patients with prior VTE are associated with an increased
      risk of recurrent VTE. METHODS: In this longitudinal observational study, we
      investigated 271 consecutive patients, aged 18 years or older, referred for
      thrombophilia investigation with an objectively diagnosed episode of VTE.
      Patients completed the depression subscale of the Hospital Anxiety and Depression
      Scale (HADS-D). During the observation period, they were contacted by phone and
      information on recurrent VTE, anticoagulation therapy, and thromboprophylaxis in
      risk situations was collected. RESULTS: Clinically relevant depressive symptoms
      (HADS-D score >= 8) were present in 10% of patients. During a median observation
      period of 13 months (range 5-48), 27 (10%) patients experienced recurrent VTE.
      After controlling for sociodemographic and clinical factors, a 3-point increase
      on the HADS-D score was associated with a 44% greater risk of recurrent VTE (OR
      1.44, 95% CI 1.02, 2.06). Compared to patients with lower levels of depressive
      symptoms (HADS-D score: range 0-2), those with higher levels (HADS-D score: range
      3-16) had a 4.1-times greater risk of recurrent VTE (OR 4.07, 95% CI 1.55,
      10.66). CONCLUSIONS: The findings suggest that depressive symptoms might
      contribute to an increased risk of recurrent VTE independent of other prognostic
      factors. An increased risk might already be present at subclinical levels of
      depressive symptoms.

PMID- 25938664
TI  - Postnatal persistent infection with classical Swine Fever virus and its
      immunological implications.
AB  - It is well established that trans-placental transmission of classical swine fever
      virus (CSFV) during mid-gestation can lead to persistently infected offspring.
      The aim of the present study was to evaluate the ability of CSFV to induce viral
      persistence upon early postnatal infection. Two litters of 10 piglets each were
      infected intranasally on the day of birth with low and moderate virulence CSFV
      isolates, respectively. During six weeks after postnatal infection, most of the
      piglets remained clinically healthy, despite persistent high virus titres in the
      serum. Importantly, these animals were unable to mount any detectable humoral and
      cellular immune response. At necropsy, the most prominent gross pathological
      lesion was a severe thymus atrophy. Four weeks after infection, PBMCs from the
      persistently infected seronegative piglets were unresponsive to both, specific
      CSFV and non-specific PHA stimulation in terms of IFN-gamma-producing cells.
      These results suggested the development of a state of immunosuppression in these
      postnatally persistently infected pigs. However, IL-10 was undetectable in the
      sera of the persistently infected animals. Interestingly, CSFV-stimulated PBMCs
      from the persistently infected piglets produced IL-10. Nevertheless, despite the
      addition of the anti-IL-10 antibody in the PBMC culture from persistently
      infected piglets, the response of the IFN-gamma producing cells was not restored.
      Therefore, other factors than IL-10 may be involved in the general suppression of
      the T-cell responses upon CSFV and mitogen activation. Interestingly, bone marrow
      immature granulocytes were increased and targeted by the virus in persistently
      infected piglets. Taken together, we provided the first data demonstrating the
      feasibility of CSFV in generating a postnatal persistent disease, which has not
      been shown for other members of the Pestivirus genus yet. Since serological
      methods are routinely used in CSFV surveillance, persistently infected pigs might
      go unnoticed. In addition to the epidemiological and economic significance of
      persistent CSFV infection, this model could be useful for understanding the
      mechanisms of viral persistence. 

PMID- 25938665
TI  - Interview with C. David Allis, PhD.

PMID- 25938666
TI  - Interobserver Agreement between On-Call Radiology Resident and General
      Radiologist Interpretations of CT Pulmonary Angiograms and CT Venograms.
AB  - OBJECTIVES: To evaluate the interobserver agreement (IOA) between the initial
      radiology resident and the final staff radiologist reports of combined computed
      tomographic pulmonary angiograms (CTPA) and computed tomographic venograms (CTV)
      performed during on-call hours. MATERIALS AND METHODS: Approval by the
      institutional review board was obtained. Six-hundred and ninety-six consecutive
      studies (CTPA or CTPA with CTV) performed during on-call hours and interpreted by
      30 residents were identified. Radiology residents' reports were compared to the
      final staff reports. Three tests outcomes were considered (positive, P; negative,
      N; indeterminate, I). Discordant cases were reviews by a chest radiologist.
      RESULTS: CTPAs were reported by staff radiologists as positive for pulmonary
      embolism (PE) in 18% (126/694), with a kappa of 0.81 (95% CI 0.77-0.86) with 3
      outcomes (P, N, I), and a kappa of 0.89 (95% CI 0.85-0.94) with 2 outcomes (P,
      N). Regarding PE location, good concordance was observed for positive studies,
      with a kappa of 0.86 (95% CI 0.78 - 0.95). CTVs were reported as positive by
      staff radiologists in 8.5% (33/388), with a kappa of 0.66 (95% CI 0.55-0.77) with
      3 outcomes (P, N, I), and a kappa of 0.89 (95% CI 0.8-1.0) with 2 outcomes (P,
      N). The IOA between residents and staff radiologists increased with increasing
      residency year level for CTPAs, but did not for CTVs. CONCLUSIONS: Very good and
      good IOA were observed between resident and staff radiologist interpretations for
      CTPA and CTV, respectively, with tendency towards improved IOA as residency level
      of training increased for CTPA, but not for CTV.

PMID- 25938667
TI  - Prevalent HLA Class II Alleles in Mexico City Appear to Confer Resistance to the
      Development of Amebic Liver Abscess.
AB  - Amebiasis is an endemic disease and a public health problem throughout Mexico,
      although the incidence rates of amebic liver abscess (ALA) vary among the
      geographic regions of the country. Notably, incidence rates are high in the
      northwestern states (especially Sonora with a rate of 12.57/100,000 inhabitants)
      compared with the central region (Mexico City with a rate of 0.69/100,000
      inhabitants). These data may be related to host genetic factors that are
      partially responsible for resistance or susceptibility. Therefore, we studied the
      association of the HLA-DRB1 and HLA-DQB1 alleles with resistance or
      susceptibility to ALA in two Mexican populations, one each from Mexico City and
      Sonora. Ninety ALA patients were clinically diagnosed by serology and sonography.
      Genomic DNA was extracted from peripheral blood mononuclear cells. To establish
      the genetic identity of both populations, 15 short tandem repeats (STRs) were
      analyzed with multiplexed PCR, and the allelic frequencies of HLA were studied by
      PCR-SSO using LUMINEX technology. The allele frequencies obtained were compared
      to an ethnically matched healthy control group (146 individuals). We observed
      that both affected populations differed genetically from the control group. We
      also found interesting trends in the population from Mexico City. HLA-DQB1*02
      allele frequencies were higher in ALA patients compared to the control group
      (0.127 vs 0.047; p= 0.01; pc= NS; OR= 2.9, 95% CI= 1.09-8.3). The less frequent
      alleles in ALA patients were HLA-DRB1*08 (0.118 vs 0.238 in controls; p= 0.01;
      pc= NS; OR= 0.42, 95% CI= 0.19-0.87) and HLA-DQB1*04 (0.109 vs 0.214; p= 0.02;
      pc= NS; OR= 0.40, 95% CI= 0.20-0.94). The haplotype HLA-DRB1*08/-DQB1*04 also
      demonstrated a protective trend against the development of this disease (0.081
      vs. 0.178; p=0.02; pc=NS; OR= 0.40, 95% CI= 0.16-0.93). These trends suggest that
      the prevalent alleles in the population of Mexico City may be associated with
      protection against the development of ALA. 

PMID- 25938668
TI  - Performance Assessment of the BluePoint MycoID Plus Kit for Identification of
      Mycobacterium tuberculosis, Including Rifampin- and Isoniazid-resistant Isolates,
      and Nontuberculous Mycobacteria.
AB  - The performance of the BluePoint MycoID plus kit (Bio Concept Corporation,
      Taichung, Taiwan), which was designed to simultaneously detect Mycobacterium
      tuberculosis (MTB), rifampin- and isoniazid-resistant MTB, and nontuberculous
      mycobacteria (NTM) was first evaluated with 950 consecutive positive cultures in
      Mycobacterium Growth Indicator Tube (MGIT) system (BACTEC, MGIT 960 system,
      Becton-Dickinson, Sparks) from clinical respiratory specimens. The discrepant
      results between kit and culture-based identification were finally assessed by 16S
      rRNA gene sequencing and clinical diagnosis. The accuracy rate of this kit for
      identification of all Mycobacterium species was 96.3% (905/940). For MTB
      identification, the sensitivity, specificity, positive predictive value (PPV) and
      negative predictive value (NPV) of the kit were 99.7%, 99.3%, 99.0% and 99.8%,
      respectively. For rifampicin-resistant MTB identification, the sensitivity,
      specificity, PPV, and NPV of the kit were 100.0%, 99.4%, 91.3%, and 100.0%,
      respectively, while the corresponding values of isoniazid-resistant MTB
      identification were 82.6%, 99.4%, 95.0%, and 97.6%, respectively. In identifying
      specific NTM species, the kit correctly identified 99.3% of M. abscessus
      (147/148) complex, 100% of M. fortuitum (32/32), M. gordonae (38/38), M. avium
      (39/39), M. intracellulare (90/90), M. kansasii (36/36), and M. avium complex
      species other than M. avium and M. intracellulare (94/94). In conclusions, the
      diagnostic value of the BluePoint MycoID plus kit was superior to culture method
      for recoveries and identification of NTM to species level. In addition, the
      diagnostic accuracy of BluePoint MycoID plus kit in MTB identification was
      similar to conventional culture method with high accuracy rate of rifampicin
      resistant M. tuberculosis identification. 

PMID- 25938669
TI  - Using community-based participatory research principles to develop more
      understandable recruitment and informed consent documents in genomic research.
AB  - BACKGROUND: Heart Healthy Lenoir is a transdisciplinary project aimed at creating
      long-term, sustainable approaches to reduce cardiovascular disease risk
      disparities in Lenoir County, North Carolina using a design spanning genomic
      analysis and clinical intervention. We hypothesized that residents of Lenoir
      County would be unfamiliar and mistrustful of genomic research, and therefore
      reluctant to participate; additionally, these feelings would be higher in African
      Americans. METHODOLOGY: To test our hypothesis, we conducted qualitative research
      using community-based participatory research principles to ensure our genomic
      research strategies addressed the needs, priorities, and concerns of the
      community. African-American (n = 19) and White (n = 16) adults in Lenoir County
      participated in four focus groups exploring perceptions about genomics and
      cardiovascular disease. Demographic surveys were administered and a semi
      structured interview guide was used to facilitate discussions. The discussions
      were digitally recorded, transcribed verbatim, and analyzed in ATLAS.ti. RESULTS
      AND SIGNIFICANCE: From our analysis, key themes emerged: transparent
      communication, privacy, participation incentives and barriers, knowledge, and the
      impact of knowing. African-Americans were more concerned about privacy and
      community impact compared to Whites, however, African-Americans were still eager
      to participate in our genomic research project. The results from our formative
      study were used to improve the informed consent and recruitment processes by: 1)
      reducing misconceptions of genomic studies; and 2) helping to foster participant
      understanding and trust with the researchers. Our study demonstrates how
      community-based participatory research principles can be used to gain deeper
      insight into the community and increase participation in genomic research
      studies. Due in part to these efforts 80.3% of eligible African-American
      participants and 86.9% of eligible White participants enrolled in the Heart
      Healthy Lenoir Genomics study making our overall enrollment 57.8% African
      American. Future research will investigate return of genomic results in the
      Lenoir community.

PMID- 25938670
TI  - Effect of User Charges on Secondary Level Surgical Care Utilization and Out-of
      Pocket Expenditures in Haryana State, India.
AB  - BACKGROUND: Generation of resources for providing health care services is an
      important issue in developing countries. User charges in the form of Surgical
      Package Program (SPP) were introduced in all district hospitals of Haryana to
      address this problem. We evaluate the effect of this SPP program on surgical care
      utilization and out-of-pocket (OOP) expenditures. METHODS: Data on 25437
      surgeries, from July 2006 to June 2013 in 3 districts of Haryana state, was
      analyzed using interrupted time series analysis to assess the impact of SPP on
      utilization of services. Adjustment was made for presence of any autocorrelation
      and seasonality effects. A cross sectional survey was undertaken among 180
      patients in District hospital, Panchkula during June 2013 to assess the extent of
      out of pocket (OOP) expenditure incurred, financial risk protection and methods
      to cope with OOP expenditure. Catastrophic health expenditure, estimated as any
      expenditure in excess of 10% of the household consumption expenditure, was used
      to assess the extent of financial risk protection. RESULTS: User charges had a
      negative effect on the number of surgeries in public sector district hospitals in
      all the 3 districts. The mean out-of-pocket expenditure incurred by the patients
      was Rs.4564 (USD 74.6). The prevalence of catastrophic expenditure was 5.6%. A
      higher proportion among the poorest 20% population coped through borrowing money
      (47.2%), while majority (86.1%) of those belonging to richest quintile paid from
      their monthly income or savings, or had insurance. CONCLUSION: There is a need to
      increase the public financing for curative services and it should be based on the
      needs of population. Any form of user charge in public sector hospitals should be
      removed.

PMID- 25938671
TI  - Trend in height of Turkish and Moroccan children living in the Netherlands.
AB  - OBJECTIVES: To study trends in height of Turkish and Moroccan immigrant children
      living in The Netherlands, to investigate the association between height and
      background characteristics in these children, and to calculate height-for-age
      references data for these groups. DESIGN: Nationwide cross-sectional data
      collection from children aged 0 to 18 years by trained professionals in 1997 and
      2009. The study population consisted of 2,822 Turkish 2,779 Moroccan, and 13,705
      Dutch origin children in 1997 and 2,548 Turkish, 2,594 Moroccan, and 11,255 Dutch
      origin children in 2009. MAIN OUTCOME MEASURES: Mean height in cm, and mean
      height standard deviation scores. RESULTS: In 2009, mean height at the age of 18
      y was similar for Turkish and Moroccan children: 177 cm for boys and 163 cm for
      girls, which was 2 to 3 cm taller than in 1997. Still, Turkish and Moroccan
      adolescents were 5.5 cm (boys) to 7 cm (girls) shorter than their Dutch peers. No
      significant differences were found in mean height standard deviation scores
      across the educational level of the parents, geographical region, primary
      language spoken at home, and immigrant generation. CONCLUSIONS: While the secular
      height increase in Dutch children came to a halt, the trend in Turkish and
      Moroccan children living in The Netherlands continued. However, large differences
      in height between Turkish and Moroccan children and Dutch children remain. We
      found no association with the background characteristics. We recommend the use of
      the new growth charts for children of Turkish and Moroccan origin who have a
      height-for-age below -2SD on the growth chart for Dutch children.

PMID- 25938672
TI  - The Veiled Economics of Employee Cost Sharing.

PMID- 25938673
TI  - Reproductive Hazards Still Persist in the Microelectronics Industry: Increased
      Risk of Spontaneous Abortion and Menstrual Aberration among Female Workers in the
      Microelectronics Industry in South Korea.
AB  - OBJECTIVES: Despite the global expansion of supply chains and changes to the
      production process, few studies since the mid-1990 s and 2000s have examined
      reproductive risks of the microelectronics industry; we examined the reproductive
      risks among female microelectronics workers in South Korea. METHODS: Based on
      claim data from the National Health Insurance (2008-2012), we estimated age
      specific rates of spontaneous abortion (SAB) and menstrual aberration (MA) among
      women aged 20 to 39 years. We compared data between microelectronics workers and
      three different control groups: economically inactive women, the working
      population as a whole, and workers employed in the bank industry. For an effect
      measure, age-stratified relative risks (RRs) were estimated. RESULTS: Female
      workers in the microelectronics industry showed significantly higher risk for SAB
      and MA compared to control groups. The RRs for SAB with reference to economically
      inactive women, working population, and bank workers in their twenties were 1.57,
      1.40, and 1.37, respectively, and the RRs for MA among females in their twenties
      were 1.54, 1.38, and 1.48, respectively. For women in their thirties, RRs for SAB
      were 1.58, 1.67, and 1.13, and those for MA were 1.25, 1.35, and 1.23 compared to
      the three control populations, respectively. All RRs were statistically
      significant at a level of 0.05, except for the SAB case comparison with bank
      workers in their thirties. CONCLUSIONS: Despite technical innovations and health
      and safety measures, female workers in microelectronics industry in South Korea
      have high rates of SAB and MA, suggesting continued exposure to reproductive
      hazards. Further etiologic studies based on primary data collection and careful
      surveillance are required to confirm these results.

PMID- 25938674
TI  - Sexual Differences in Cell Loss during the Post-Hatch Development of Song Control
      Nuclei in the Bengalese Finch.
AB  - Birdsongs and the regions of their brain that control song exhibit obvious sexual
      differences. However, the mechanisms underlying these sexual dimorphisms remain
      unknown. To address this issue, we first examined apoptotic cells labeled with
      caspase-3 or TUNEL in Bengalese finch song control nuclei - the robust nucleus of
      the archopallium (RA), the lateral magnocellular nucleus of the anterior
      nidopallium (LMAN), the high vocal center (HVC) and Area X from post-hatch day
      (P) 15 to 120. Next, we investigated the expression dynamics of pro-apoptotic
      (Bid, Bad and Bax) and anti-apoptotic (Bcl-2 and Bcl-xL) genes in the
      aforementioned nuclei. Our results revealed that the female RA at P45 exhibited
      marked cell apoptosis, confirmed by low densities of Bcl-xL and Bcl-2. Both the
      male and female LMAN exhibited apoptotic peaks at P35 and P45, respectively, and
      the observed cell loss was more extensive in males. A corresponding sharp
      decrease in the density of Bcl-2 after P35 was observed in both sexes, and a
      greater density of Bid was noted at P45 in males. In addition, we observed that
      RA volume and the total number of BDNF-expressing cells decreased significantly
      after unilateral lesion of the LMAN or HVC (two areas that innervate the RA) and
      that greater numbers of RA-projecting cells were immunoreactive for BDNF in the
      LMAN than in the HVC. We reasoned that a decrease in the amount of BDNF
      transported via HVC afferent fibers might result in an increase in cell apoptosis
      in the female RA. Our data indicate that cell apoptosis resulting from different
      pro- and anti-apoptotic agents is involved in generating the differences between
      male and female song control nuclei. 

PMID- 25938675
TI  - Is demography destiny? Application of machine learning techniques to accurately
      predict population health outcomes from a minimal demographic dataset.
AB  - For years, we have relied on population surveys to keep track of regional public
      health statistics, including the prevalence of non-communicable diseases. Because
      of the cost and limitations of such surveys, we often do not have the up-to-date
      data on health outcomes of a region. In this paper, we examined the feasibility
      of inferring regional health outcomes from socio-demographic data that are widely
      available and timely updated through national censuses and community surveys.
      Using data for 50 American states (excluding Washington DC) from 2007 to 2012, we
      constructed a machine-learning model to predict the prevalence of six non
      communicable disease (NCD) outcomes (four NCDs and two major clinical risk
      factors), based on population socio-demographic characteristics from the American
      Community Survey. We found that regional prevalence estimates for non
      communicable diseases can be reasonably predicted. The predictions were highly
      correlated with the observed data, in both the states included in the derivation
      model (median correlation 0.88) and those excluded from the development for use
      as a completely separated validation sample (median correlation 0.85),
      demonstrating that the model had sufficient external validity to make good
      predictions, based on demographics alone, for areas not included in the model
      development. This highlights both the utility of this sophisticated approach to
      model development, and the vital importance of simple socio-demographic
      characteristics as both indicators and determinants of chronic disease. 

PMID- 25938676
TI  - Correction: Protective Effect of Indole-3-Pyruvate against Ultraviolet B-Induced
      Damage to Cultured HaCaT Keratinocytes and the Skin of Hairless Mice.

PMID- 25938677
TI  - Relationships among Body Condition, Insulin Resistance and Subcutaneous Adipose
      Tissue Gene Expression during the Grazing Season in Mares.
AB  - Obesity and insulin resistance have been shown to be risk factors for laminitis
      in horses. The objective of the study was to determine the effect of changes in
      body condition during the grazing season on insulin resistance and the expression
      of genes associated with obesity and insulin resistance in subcutaneous adipose
      tissue (SAT). Sixteen Finnhorse mares were grazing either on cultivated high
      yielding pasture (CG) or semi-natural grassland (NG) from the end of May to the
      beginning of September. Body measurements, intravenous glucose tolerance test
      (IVGTT), and neck and tailhead SAT gene expressions were measured in May and
      September. At the end of grazing, CG had higher median body condition score (7
      vs. 5.4, interquartile range 0.25 vs. 0.43; P=0.05) and body weight (618 kg vs.
      572 kg +/- 10.21 (mean +/- SEM); P=0.02), and larger waist circumference (P=0.03)
      than NG. Neck fat thickness was not different between treatments. However,
      tailhead fat thickness was smaller in CG compared to NG in May (P=0.04), but this
      difference disappeared in September. Greater basal and peak insulin
      concentrations, and faster glucose clearance rate (P=0.03) during IVGTT were
      observed in CG compared to NG in September. A greater decrease in plasma non
      esterified fatty acids during IVGTT (P<0.05) was noticed in CG compared to NG
      after grazing. There was down-regulation of insulin receptor, retinol binding
      protein 4, leptin, and monocyte chemoattractant protein-1, and up-regulation of
      adiponectin (ADIPOQ), adiponectin receptor 1 and stearoyl-CoA desaturase (SCD)
      gene expressions in SAT of both groups during the grazing season (P<0.05).
      Positive correlations were observed between ADIPOQ and its receptors and between
      SCD and ADIPOQ in SAT (P<0.01). In conclusion, grazing on CG had a moderate
      effect on responses during IVGTT, but did not trigger insulin resistance.
      Significant temporal differences in gene expression profiles were observed during
      the grazing season. 

PMID- 25938678
TI  - The Synthesis, Characterization and Reactivity of a Series of Ruthenium N-triphos
      Ph Complexes.
AB  - Herein we report the synthesis of a tridentate phosphine ligand N(CH2PPh2)3 (N
      triphos(Ph)) (1) via a phosphorus based Mannich reaction of the hydroxylmethylene
      phosphine precursor with ammonia in methanol under a nitrogen atmosphere. The N
      triphos(Ph) ligand precipitates from the solution after approximately 1 hr of
      reflux and can be isolated analytically pure via simple cannula filtration
      procedure under nitrogen. Reaction of the N-triphos(Ph) ligand with [Ru3(CO)12]
      under reflux affords a deep red solution that show evolution of CO gas on ligand
      complexation. Orange crystals of the complex [Ru(CO)2{N(CH2PPh2)3}-kappa(3)P] (2)
      were isolated on cooling to RT. The (31)P{(1)H} NMR spectrum showed a
      characteristic single peak at lower frequency compared to the free ligand.
      Reaction of a toluene solution of complex 2 with oxygen resulted in the
      instantaneous precipitation of the carbonate complex [Ru(CO3)(CO){N(CH2PPh2)3}
      kappa(3)P] (3) as an air stable orange solid. Subsequent hydrogenation of 3 under
      15 bar of hydrogen in a high-pressure reactor gave the dihydride complex
      [RuH2(CO){N(CH2PPh2)3}-kappa(3)P] (4), which was fully characterized by X-ray
      crystallography and NMR spectroscopy. Complexes 3 and 4 are potentially useful
      catalyst precursors for a range of hydrogenation reactions, including biomass
      derived products such as levulinic acid (LA). Complex 4 was found to cleanly
      react with LA in the presence of the proton source additive NH4PF6 to give
      [Ru(CO){N(CH2PPh2)3}-kappa(3)P{CH3CO(CH2)2CO2H}-kappa(2)O](PF6) (6). 

PMID- 25938679
TI  - Breast Cancer: Diffusion Kurtosis MR Imaging-Diagnostic Accuracy and Correlation
      with Clinical-Pathologic Factors.
AB  - PURPOSE: To assess diagnostic accuracy with diffusion kurtosis imaging (DKI) in
      patients with breast lesions and to evaluate the potential association between
      DKI-derived parameters and breast cancer clinical-pathologic factors. MATERIALS
      AND METHODS: Institutional review board approval and written informed consent
      were obtained. Data from 97 patients (mean age +/- standard deviation, 45.7 years
      +/- 13.1; range, 19-70 years) with 98 lesions (57 malignant and 41 benign) who
      were treated between January 2014 and April 2014 were retrospectively analyzed.
      DKI (with b values of 0-2800 sec/mm(2)) and conventional diffusion-weighted
      imaging data were acquired. Kurtosis and diffusion coefficients from DKI and
      apparent diffusion coefficients from diffusion-weighted imaging were measured by
      two radiologists. Student t test, Wilcoxon signed-rank test, Jonckheere-Terpstra
      test, receiver operating characteristic curves, and Spearman correlation were
      used for statistical analysis. RESULTS: Kurtosis coefficients were significantly
      higher in the malignant lesions than in the benign lesions (1.05 +/- 0.22 vs 0.65
      +/- 0.11, respectively; P < .0001). Diffusivity and apparent diffusion
      coefficients in the malignant lesions were significantly lower than those in the
      benign lesions (1.13 +/- 0.27 vs 1.97 +/- 0.33 and 1.02 +/- 0.18 vs 1.48 +/-
      0.33, respectively; P < .0001). Significantly higher specificity for
      differentiation of malignant from benign lesions was shown with the use of
      kurtosis and diffusivity coefficients than with the use of apparent diffusion
      coefficients (83% [34 of 41] and 83% [34 of 41] vs 76% [31 of 41], respectively;
      P < .0001) with equal sensitivity (95% [54 of 57]). In patients with invasive
      breast cancer, kurtosis was positively correlated with tumor histologic grade (r
      = 0.75) and expression of the Ki-67 protein (r = 0.55). Diffusivity was
      negatively correlated with tumor histologic grades (r = -0.44) and Ki-67
      expression (r = -0.46). CONCLUSION: DKI showed higher specificity than did
      conventional diffusion-weighted imaging for assessment of benign and malignant
      breast lesions. Patients with grade 3 breast cancer or tumors with high
      expression of Ki-67 were associated with higher kurtosis and lower diffusivity
      coefficients; however, this association must be confirmed in prospective studies.

PMID- 25938680
TI  - Inhibition of the aggregation of lactoferrin and (-)-epigallocatechin gallate in
      the presence of polyphenols, oligosaccharides, and collagen peptide.
AB  - The aggregation of lactoferrin and (-)-epigallocatechin gallate (EGCG) was
      inhibited by polyphenols, oligosaccharides, and collagen peptide in this study.
      Polyphenols, oligosaccharides, or collagen peptide can effectively prevent the
      formation of lactoferrin-EGCG aggregates, respectively. The addition sequence of
      lactoferrin, polyphenols (oligosaccharides or collagen peptide) and EGCG can
      affect the turbidity and particle size of the ternary complexes in the buffer
      solution; however, it hardly affected the zeta-potential and fluorescence
      characteristics. With either positive or negative charge, polyphenols and
      collagen peptide disrupted the formation of lactoferrin-EGCG aggregate mainly
      through the mechanism of its competition with EGCG molecules which surrounded the
      lactoferrin molecule surface with weaker binding affinities, forming polyphenols
      or a collagen peptide-lactoferrin-EGCG ternary complex; for neutral
      oligosaccharides, the ternary complex was generated mainly through steric
      effects, accompanied by a change in the lactoferrin secondary structure induced
      by gallic acid, chlorogenic acid, and xylo-oligosaccharide. Polyphenols,
      oligosaccharides, or collagen peptide restraining the formation of lactoferrin
      EGCG aggregate could be applied in the design of clear products in the food,
      pharmaceutical, and cosmetic industries. 

PMID- 25938681
TI  - Effect of Breastfeeding Promotion on Early Childhood Caries and Breastfeeding
      Duration among 5 Year Old Children in Eastern Uganda: A Cluster Randomized Trial.
AB  - BACKGROUND: Although several studies have shown short term health benefits of
      exclusive breastfeeding (EBF), its long term consequences have not been studied
      extensively in low-income contexts. This study assessed the impact of an EBF
      promotion initiative for 6 months on early childhood caries (ECC) and
      breastfeeding duration in children aged 5 years in Mbale, Eastern Uganda.
      METHODS: Participants were recruited from the Ugandan site of the PROMISE- EBF
      cluster randomised trial (ClinicalTrials.gov no: NCT00397150). A total of 765
      pregnant women from 24 clusters were included in the ratio 1:1 to receive peer
      counselled promotion of EBF as the intervention or standard of care. At the 5
      year follow-up, ECC was recorded under field conditions using the World Health
      Organization's decayed missing filled tooth (dmft) index. Adjusted negative
      binomial and linear regression were used in the analysis. RESULTS: Mean
      breastfeeding duration in the intervention and control groups (n=417) were 21.8
      (CI 20.7-22.9) and 21.3(CI 20.7-21.9) months, respectively. The mean dmft was 1.5
      (standard deviation [SD] 2.9) and 1.7 (SD 2.9) in the intervention and control
      groups, respectively. Corresponding prevalence estimates of ECC were 38% and 41%.
      Negative binomial regression analysis adjusted for cluster effects and loss-to
      follow-up by inverse probability weights (IPW) showed an incidence-rate ratio
      (IRR) of 0.91 (95% CI 0.65-1.2). Comparing the effect of the trial arm on
      breastfeeding duration showed a difference in months of 0.48 (-0.72 to 1.7).
      CONCLUSION: PROMISE EBF trial did not impact on early childhood caries or
      breastfeeding duration at 5 years of age. This study contributes to the body of
      evidence that promotion of exclusive breastfeeding does not raise oral health
      concerns. However, the high burden of caries calls for efforts to improve the
      oral health condition in this setting. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00397150.

PMID- 25938682
TI  - Observation of nanometer-sized electro-active defects in insulating layers by
      fluorescence microscopy and electrochemistry.
AB  - We report a method to study electro-active defects in passivated electrodes. This
      method couples fluorescence microscopy and electrochemistry to localize and size
      electro-active defects. The method was validated by comparison with a scanning
      probe technique, scanning electrochemical microscopy. We used our method for
      studying electro-active defects in thin TiO2 layers electrodeposited on 25 MUm
      diameter Pt ultramicroelectrodes (UMEs). The permeability of the TiO2 layer was
      estimated by measuring the oxidation of ferrocenemethanol at the UME. Blocking of
      current ranging from 91.4 to 99.8% was achieved. Electro-active defects with an
      average radius ranging between 9 and 90 nm were observed in these TiO2 blocking
      layers. The distribution of electro-active defects over the TiO2 layer is highly
      inhomogeneous and the number of electro-active defect increases for lower degree
      of current blocking. The interest of the proposed technique is the possibility to
      quickly (less than 15 min) image samples as large as several hundreds of MUm(2)
      while being able to detect electro-active defects of only a few tens of nm in
      radius. 

PMID- 25938683
TI  - A serum vitamin D level <25nmol/l pose high tuberculosis risk: a meta-analysis.
AB  - BACKGROUND: Low serum Vitamin D is considered to be associated with tuberculosis
      while the "dangerous" level was not clear. The aim of this study was to identify
      the association between tuberculosis and serum Vitamin D levels via synthesis of
      available evidence. METHODS: A search of EMBASE, Medline, ISI Web of knowledge,
      and Pubmed was conducted. The number of subjects of tuberculosis and no
      tuberculosis groups in four Vitamin D range. Meta-analyses were performed and
      presented by odds ratios (ORs) and corresponding 95% confidence intervals (CIs).
      RESULTS: A total of 15 studies involving 1440 cases and 2558 controls were
      included. A significantly increased risk of tuberculosis was found in two ranges:
      <= 12.5 nmol/L: pooled OR = 4.556, 95% CI = 2.200-9.435; 13-25 nmol/L: pooled OR
      = 3.797, 95% CI = 1.935-7.405. No statistically significant risk of tuberculosis
      was found in the range of 26-50 nmol/L (pooled OR = 1.561, 95% CI =0.997-2.442).
      In range 51-75 nmol/L, no positive association was found (pooled OR =1.160, 95%
      CI = 0.708-1.900). CONCLUSIONS: This study found that a serum Vitamin D level <=
      25 nmol/L was significantly associated with an increased risk of tuberculosis
      while the range of 51-75 nmol/L was not. The range 26-50nmol/L posed potential
      high tuberculosis risk. Future large-scale, well-designed studies are needed to
      verify these results.

PMID- 25938684
TI  - Eucalyptus pollen allergy and asthma in children: a cross-sectional study in
      South-East Queensland, Australia.
AB  - OBJECTIVES: To investigate Eucalyptus (gum tree) pollen allergy in children in
      relation to geography, particularly vegetation, and its relationship to asthma.
      METHODS: Males (n = 180) and females (n = 200) aged 9 to 14 participated. Some
      were healthy (asymptomatic), some had asthma, and some had other symptoms
      associated with atopy. School students were from three urban coastal schools and
      one school from a nearby semi-rural elevated area (range) near Brisbane,
      Australia. Coastal and range locations featured different distributions of
      Myrtaceae family vegetation (including Eucalyptus, Melaleuca, Leptospermum
      species). Skin prick test (SPT) responses to 15 commercial allergens were
      compared. As well, responses from coast versus range groups, and 'asthma' (n =
      97) versus 'healthy' status (n = 107) groups, were compared. RESULTS: SPT
      responses (>=3mm wheal diameter) indicate that children with asthma are 31.1
      times more likely to be allergic to Eucalyptus pollen extract (OR: 31.1; 95%CI
      4.1- 235.7) compared to healthy children. Dust mite (p = .018), Eucalyptus (p =
      .046) and cockroach (p = .047) allergen SPT responses (wheals >=3mm) were
      significantly greater in participants located on the coast versus range as
      determined by Fisher's Exact Test (alpha .05). For each location, percentage of
      positive responses (wheals >=3mm) was greatest for 'dust mite' (30.9%-46%),
      'cockroach' (18.1% -35%) and 'Bermuda grass' (10.6%-19.4%). CONCLUSIONS: The
      results support the hypothesis that proximity to Myrtaceae vegetation is related
      to positive SPT response and that Eucalyptus is an important allergen for
      children with asthma. Substantial response to olive allergen, in the absence of
      olive trees, suggests that the response may be driven by substances in other
      plants, perhaps Melaleuca quinquenervia, which abounds in coastal areas.
      IMPLICATIONS: Response to Eucalyptus allergen indicates that changes in gardening
      practice in schools and public areas may be appropriate. The findings pose
      validity questions regarding the use of some commercial allergens due to cross
      reactive responses and the sources of those responses.

PMID- 25938685
TI  - The effect of circadian rhythm on pharmacokinetics and metabolism of the Cdk
      inhibitor, roscovitine, in tumor mice model.
AB  - Roscovitine is a selective Cdk-inhibitor that is under investigation in phase II
      clinical trials under several conditions, including chemotherapy. Tumor growth
      inhibition has been previously shown to be affected by the dosing time of
      roscovitine in a Glasgow osteosarcoma xenograft mouse model. In the current
      study, we examined the effect of dose timing on the pharmacokinetics,
      biodistribution and metabolism of this drug in different organs in B6D2F1 mice.
      The drug was orally administered at resting (ZT3) or activity time of the mice
      (ZT19) at a dose of 300 mg/kg. Plasma and organs were removed at serial time
      points (10, 20 and 30 min; 1, 2, 4, 6, 8, 12 and 24 h) after the administration.
      Roscovitine and its carboxylic metabolite concentrations were analyzed using HPLC
      UV, and pharmacokinetic parameters were calculated in different organs. We found
      that systemic exposure to roscovitine was 38% higher when dosing at ZT3, and
      elimination half-life was double compared to when dosing at ZT19. Higher organ
      concentrations expressed as (organ/plasma) ratio were observed when dosing at ZT3
      in the kidney (180%), adipose tissue (188%), testis (132%) and lungs (112%),
      while the liver exposure to roscovitine was 120% higher after dosing at ZT19. The
      metabolic ratio was approximately 23% higher at ZT19, while the intrinsic
      clearance (CLint) was approximately 67% higher at ZT19, indicating faster and
      more efficient metabolism. These differences may be caused by circadian
      differences in the absorption, distribution, metabolism and excretion processes
      governing roscovitine disposition in the mice. In this article, we describe for
      the first time the chronobiodistribution of roscovitine in the mouse and the
      contribution of the dosing time to the variability of its metabolism. Our results
      may help in designing better dosing schedules of roscovitine in clinical trials. 

PMID- 25938686
TI  - Physiological functions of vitamin D: what we have learned from global and
      conditional VDR knockout mouse studies.
AB  - The physiological role of vitamin D depends on calcium supply and calcium
      balance. When the calcium balance is normal, the major target of vitamin D is
      intestine. Vitamin D stimulates mainly active intestinal calcium transport
      mechanism. During a negative calcium balance, bone effects of vitamin D become
      dominant. Thus, the role of vitamin D in maintaining normocalcemia appears to
      have priority over skeletal integrity in these situations. 

PMID- 25938687
TI  - Efficient Tailoring of Upconversion Selectivity by Engineering Local Structure of
      Lanthanides in Na(x)REF(3+x) Nanocrystals.
AB  - Efficient tailoring of upconversion emissions in lanthanide-doped nanocrystals is
      of great significance for extended optical applications. Here, we present a
      facile and highly effective method to tailor the upconversion selectivity by
      engineering the local structure of lanthanides in Na(x)REF(3+x) nanocrystals. The
      local structure engineering was achieved through precisely tuning the composition
      of nanocrystals, with different [Na]/[RE] ([F]/[RE]) ratio. It was found that the
      lattice parameter as well as the coordination number and local symmetry of
      lanthanides changed with the composition. A significant difference in the red to
      green emission ratio, which varied from 1.9 to 71 and 1.6 to 116, was observed
      for Na(x)YF(3+x):Yb,Er and Na(x)GdF(3+x):Yb,Er nanocrystals, respectively.
      Moreover, the local structure-dependent upconversion selectivity has been
      verified for Na(x)YF(3+x):Yb,Tm nanocrystals. In addition, the local structure
      induced upconversion emission from Er(3+) enhanced 9 times, and the CaF2 shell
      grown epitaxially over the nanocrystals further promoted the red emission by 450
      times, which makes it superior as biomarkers for in vivo bioimaging. These
      exciting findings in the local structure-dependent upconversion selectivity not
      only offer a general approach to tailoring lanthanide related upconversion
      emissions but also benefit multicolor displays and imaging.

PMID- 25938688
TI  - Induction and escalation therapies in multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic demyelinating disease affecting the central
      nervous system. Pharmacological therapy of MS includes symptomatic drugs,
      treatment for relapses (corticosteroid and intravenous immunoglobulin) and
      disease modifying drugs (DMDs) defined as pharmacological agents that have an
      impact on relapse rate, disability accumulation and radiological outcomes. Two
      different therapeutic approaches are widely used in MS: escalation and induction
      therapy. Escalation therapy consists of an early start with first line DMDs (beta
      interferon, glatiramer acetate, teriflunomide, dimethyl fumarate) and if DMDs are
      ineffective or partially effective, switching to second line drugs (mitoxantrone,
      natalizumab, fingolimod). Induction therapy consists of the early use of
      immunosuppressant drugs followed by long-term maintenance treatment, generally
      with immunomodulatory agents. While the use of natalizumab and fingolimod as
      first line drugs is indicated for aggressive forms of MS, the indication for
      mitoxantrone as an induction treatment arises from randomized studies
      demonstrating that induction therapy with mitoxantrone followed by DMD
      maintenance is more effective than monotherapy with beta interferon. However, the
      safety profile of induction drugs indicates this is not an acceptable therapeutic
      strategy for all MS patients in all phases of the disease. The upcoming challenge
      is to identify patients at high risk of disability development from their
      clinical characteristics, radiological findings or biomarkers. Furthermore,
      future studies to establish an individual safety profile stratification are
      needed. 

PMID- 25938689
TI  - A Novel Technique for Distal Shunt Revision: Retrospective Analysis of Guidewire
      Assisted Distal Catheter Replacement.
AB  - BACKGROUND: Ventriculoperitoneal shunt revision is a common procedure.
      Disconnection and fracture of the distal catheter remain a common cause of
      ventriculoperitoneal shunt malfunction. OBJECTIVE: To describe a novel procedure
      for peritoneal replacement of the distal catheter by using a guidewire and a
      modified Seldinger technique (guidewire-assisted distal catheter replacement) and
      retrospectively evaluate the results of the surgical procedure. METHODS: Between
      September 2005 and December 2013, 68 patients were treated by a single surgeon
      (DMW) with distal catheter replacement using our technique. In brief, the
      previously placed distal catheter was exposed at its entry site into the abdomen.
      A soft guidewire with hydrophilic coating was inserted down the distal catheter
      into the peritoneum. The distal catheter was then removed over the guidewire,
      leaving the guidewire in place. A peel-away sheath and dilator were then inserted
      over the guidewire, and the dilator and guidewire were removed. The new distal
      catheter was then passed from the valve to the abdomen and was then fed through
      the peel-away sheath into the peritoneum. Charts were retrospectively reviewed
      for preoperative presentation, operative technique, and postoperative outcome.
      Records were specifically examined for any early or late complications. RESULTS:
      The mean patient age at surgery was 13 years. No immediate acute complications
      were noted. Of the 68 total patients, 45 patients had more than 6 months of
      follow-up. Of the 68 patients, 7 patients required another distal revision after
      guidewire-assisted distal catheter replacement. CONCLUSION: Distal shunt
      malfunction due to a mechanical failure is a common reason for shunt revision. We
      describe a technique for guidewire-assisted distal catheter replacement.

PMID- 25938690
TI  - Letter: Volumetric Arc Therapy (RapidArc) vs Gamma Knife Radiosurgery for
      Multiple Brain Metastases: Not Only a Dosimetric Issue.

PMID- 25938691
TI  - In Reply: Stereotactic Microanatomy of the Nucleus Accumbens Stimulation for
      Obsessive-Compulsive Disorder: Reported Coordinates and Mavridis' Area.

PMID- 25938692
TI  - Measuring physical neighborhood quality related to health.
AB  - Although sociodemographic factors are one aspect of understanding the effects of
      neighborhood environments on health, equating neighborhood quality with
      socioeconomic status ignores the important role of physical neighborhood
      attributes. Prior work on neighborhood environments and health has relied
      primarily on level of socioeconomic disadvantage as the indicator of neighborhood
      quality without attention to physical neighborhood quality. A small but
      increasing number of studies have assessed neighborhood physical characteristics.
      Findings generally indicate that there is an association between living in
      deprived neighborhoods and poor health outcomes, but rigorous evidence linking
      specific physical neighborhood attributes to particular health outcomes is
      lacking. This paper discusses the methodological challenges and limitations of
      measuring physical neighborhood environments relevant to health and concludes
      with proposed directions for future work. 

PMID- 25938693
TI  - PCB1254 exposure contributes to the abnormalities of optomotor responses and
      influence of the photoreceptor cell development in zebrafish larvae.
AB  - Polychlorinated biphenyls (PCBs), a group of highly toxic environmental
      pollutants, have been report to influence the visual system development in
      children. However, the underlying mechanism is unclear. The study was aim to
      investigate the effects of continuous PCBs exposure on optomotor response (OMR)
      and retinal photoreceptor cell development-related gene expression in zebrafish
      larvae. The fertilized zebrafish embryos were exposed to PCBs at concentrations
      of 0.125, 0.25, 0.5, and 1mg/L until 7 days post-fertilization. Control groups
      with blank and 0.01% methanol were also prepared. OMR test was used to detect the
      visual behavior. The mRNA expression of the CRX, RHO, SWS1, and SWS2 was assessed
      by the Quantitative Real-Time PCR. The OMR test showed that the visual behavior
      of the larvae was most sensitive when the grating spatial frequency was 0.20LP/mm
      and the moving speed was 25cm/s. Moreover, the proportion of positively swimming
      fish was significantly reduced in the 0.5 and 1mg/L PCB1254 treatment group
      (P<0.05) compared with the controls. In addition, the expression of SWS2 was
      significantly down-regulated in all PCB1254 treatment groups (P<0.05), whereas
      the decreased expression of the CRX, RHO and SWS1 was found in the 0.5 and 1mg/L
      PCB1254 groups (P<0.05). This is the first report to demonstrate that continue
      exposure of zebrafish larvae to PCBs causes photoreceptor cell development
      related gene expression changes that lead to OMR behavioral alterations. Analysis
      of these visual behavioral paradigms may be useful in predicting the adverse
      effects of toxicants on visual function in fish. 

PMID- 25938694
TI  - Nested interactions in the combined toxicity of uranium and cadmium to the
      nematode Caenorhabditis elegans.
AB  - Uranium is a natural, ubiquitous radioactive element for which elevated
      concentrations can be found in the vicinity of some nuclear fuel cycle facilities
      or intensive farming areas, and most often in mixtures with other contaminants
      such as cadmium, due to co-occurrence in geological ores (e.g. U- or P-ore). The
      study of their combined effects on ecosystems is of interest to better
      characterize such multi-metallic polluted sites. In the present study, the
      toxicity of binary mixture of U and Cd on physiological parameters of the soil
      nematode Caenorhabditis elegans was assessed over time. Descriptive modeling
      using concentration and response addition reference models was applied to compare
      observed and expected combined effects and identify possible synergistic or
      antagonistic interactions. A strong antagonism between U and Cd was identified
      for length increase and brood size endpoints. The study revealed that the
      combined effects might be explained by two nested antagonistic interactions. We
      demonstrate that the first interaction occurred in the exposure medium. We also
      identified a significant second antagonistic interaction which occurred either
      during the toxicokinetic or toxicodynamic steps. These findings underline the
      complexity of interactions that may take place between chemicals and thus,
      highlight the importance of studying mixtures at various levels to fully
      understand underlying mechanisms. 

PMID- 25938695
TI  - Ryegrass cv. Lema and guava cv. Paluma biomonitoring suitability for estimating
      nutritional contamination risks under seasonal climate in Southeastern Brazil.
AB  - The risks posed by nutrient deposition due to air pollution on ecosystems and
      their respective services to human beings can be appropriately estimated by
      bioindicator plants when they are well acclimated to the study region
      environmental conditions. This assumption encouraged us to comparatively evaluate
      the accumulation potential of ryegrass cv. Lema and guava cv. Paluma macro and
      micronutrients. We also indicated the most appropriate species for biomonitoring
      nutrient contamination risks in tropical areas of Southeastern Brazil, which are
      characterized by marked dry and wet seasons and complex mixtures of air
      pollutants from different sources (industries, vehicle traffic and agriculture).
      The study was conducted in 14 sites with different neighboring land uses, within
      the Metropolitan Region of Campinas, central-eastern region of Sao Paulo State.
      The exposure experiments with ryegrass and guava were consecutively repeated 40
      (28 days each) and 12 (84 days each) times, respectively, from Oct/2010 to
      Sept/2013. Macro and micronutrients were analyzed and background concentrations
      and enrichment ratios (ER) were estimated to classify the contamination risk
      within the study region. Significantly higher ER suggested that ryegrass were the
      most appropriate accumulator species for N, S, Mg, Fe, Mn, Cu and Zn deposition
      and guava for K, Ca, P and B deposition. Based on these biomonitoring
      adjustments, we concluded that the nutrient deposition was spatially homogeneous
      in the study area, but clear seasonality in the contamination risk by nutritional
      inputs was evidenced. Significantly higher contamination risk by S, Fe, K and B
      occurred during the dry season and enhanced contamination risk by Mn, Cu and Zn
      were highlighted during the wet season. Distinctly high contamination risk was
      estimated for S, Fe and Mn in several exposure experiments. 

PMID- 25938696
TI  - Evaluation of histopathological alterations in the gills of Vardar chub (Squalius
      vardarensis Karaman) as an indicator of river pollution.
AB  - Quantification of histopathological alterations in the gills of Vardar chub
      (Squalius vardarensis Karaman) was performed in 2012 in rivers of north-eastern
      Macedonia, with the aim to examine the effects of water quality in the rivers
      (Zletovska and Kriva River-impacted by active Pb/Zn mines; Bregalnica River
      contaminated by agricultural waste). The biological alterations in chub were
      classified as: circulatory disturbances, regressive and progressive changes, but
      their severity differed. Altogether the mildest changes were observed in the
      gills of chub from the Bregalnica River, a less polluted river, whereas mining
      impacted rivers were characterized by more severe alterations. In the gills of
      chub from the Zletovska River, which is highly contaminated with numerous metals,
      sulphates and chlorides, the highest lesion indices were found for the regressive
      changes of both epithelium and supporting tissue, with typical lesions referring
      to atrophy, thinning and lifting of epithelial cells, necrosis of epithelium and
      chloride cells, as well as deformations of lamellar cartilaginous base. Gill
      damages of chub from the Kriva River were overall milder compared to the
      Zletovska River, in accordance with pollution status. In the gills of chub from
      that river, progressive changes were more pronounced, specifically severe
      hyperplasia of mucous cells and epithelium in the interlammellar space, leading
      to fusion of lamellae, as well as hypertrophy of chloride cells. The comparison
      between seasons indicated higher intensity of progressive changes in all three
      rivers in autumn, when water level was very low, and consequently, water
      contamination was more pronounced due to concentration effect. The pattern and
      severity of histopathological alterations in the chub gills reflected differences
      in contamination levels and type of contaminants in different rivers and sampling
      periods, and thus have been proven as a valuable indicator of water quality. 

PMID- 25938697
TI  - Ecotoxicological assessment of the micelle encapsulator F-500.
AB  - Surfactants are synthetic chemicals utilized as detergents and cleaning products
      or as dispersants and emulsifiers to face water pollution. In spite of this, due
      to their wide diffusion, surfactants can induce water and soil pollution, notably
      in developed countries, and can be toxic to organisms. Taking into account that
      the assessment of new compounds is mandatory in the European Union, in this
      research the ecotoxicity of fire-fighting micelle encapsulator F-500, newly
      utilized as dispersant in seawaters polluted with oil dumping, was evaluated. The
      assessment was carried out on a battery of test-organisms (freshwater algae,
      crustaceans, and larval fish; seawater algae, crustaceans, and bivalves; soil
      earthworms, and seeds) as well as on cultured cells (L-929 mouse fibroblasts),
      which were exposed to F-500 concentrations. According to the toxicity thresholds
      provided by GESAMP, F-500 resulted to be slightly or moderately toxic to all test
      organisms, excluding the freshwater alga Pseudokirchneriella subcapitata that
      suffered highly toxic effects with IC50 values ranging from 0.21 to 0.49mg/L. The
      IC50 for mouse fibroblasts was 5.41ug/L after 24h treatment. 

PMID- 25938698
TI  - Investigation on removal of malachite green using EM based compost as adsorbent.
AB  - The discarded materials from different sources can be utilized as effective
      materials in wastewater remediation. This proposed study was aimed mainly to
      investigate the possibility of Effective Microorganisms based compost (EMKC),
      which is derived from the kitchen solid waste, as a non-conventional low cost
      adsorbent for the removal of malachite green from aqueous solution. Batch
      experiments were carried out to evaluate the optimum operating parameters like pH
      (2-9), initial dye concentration (50-1000mg/L), adsorbent particle size (0.6
      2.36mm) and adsorbent dosage (2-12g/L). EMKC recorded maximum uptake of 136.6mg/g
      of MG at pH 8, initial dye concentration 1000mg/L, adsorbent particle size 1.18mm
      and adsorbent dosage 4g/L. Two and three parameter adsorption models were
      employed to describe experimental biosorption isotherm data. The results revealed
      that the Sips model resulted in better fit than other models. The pseudo-first
      and -second order models were applied to describe kinetic data, of which the
      pseudo-second order described experimental data better with high correlation
      coefficient. This investigation suggested that EMKC could be an effective and low
      cost material for the removal of malachite green dye from aqueous solution. 

PMID- 25938699
TI  - How to Ignite an Atmospheric Pressure Microwave Plasma Torch without Any
      Additional Igniters.
AB  - This movie shows how an atmospheric pressure plasma torch can be ignited by
      microwave power with no additional igniters. After ignition of the plasma, a
      stable and continuous operation of the plasma is possible and the plasma torch
      can be used for many different applications. On one hand, the hot (3,600 K gas
      temperature) plasma can be used for chemical processes and on the other hand the
      cold afterglow (temperatures down to almost RT) can be applied for surface
      processes. For example chemical syntheses are interesting volume processes. Here
      the microwave plasma torch can be used for the decomposition of waste gases which
      are harmful and contribute to the global warming but are needed as etching gases
      in growing industry sectors like the semiconductor branch. Another application is
      the dissociation of CO2. Surplus electrical energy from renewable energy sources
      can be used to dissociate CO2 to CO and O2. The CO can be further processed to
      gaseous or liquid higher hydrocarbons thereby providing chemical storage of the
      energy, synthetic fuels or platform chemicals for the chemical industry.
      Applications of the afterglow of the plasma torch are the treatment of surfaces
      to increase the adhesion of lacquer, glue or paint, and the sterilization or
      decontamination of different kind of surfaces. The movie will explain how to
      ignite the plasma solely by microwave power without any additional igniters,
      e.g., electric sparks. The microwave plasma torch is based on a combination of
      two resonators - a coaxial one which provides the ignition of the plasma and a
      cylindrical one which guarantees a continuous and stable operation of the plasma
      after ignition. The plasma can be operated in a long microwave transparent tube
      for volume processes or shaped by orifices for surface treatment purposes. 

PMID- 25938700
TI  - Consequences of interpersonal spin on couple-relevant goal progress and
      relationship satisfaction in romantic relationships.
AB  - Large fluctuations in a person's interpersonal behavior across situations and
      over time are thought to be associated with poor personal and interpersonal
      outcomes. This study examined 2 outcomes, relationship satisfaction and goal
      progress, that could be associated with individual differences in dispersion of
      interpersonal behavior (interpersonal spin) in romantic relationships. Need
      satisfaction and perceived autonomy support for goal pursuit from the partner
      were examined as mediator variables. Spin was measured using an event-contingent
      recording (ECR) methodology with a sample of 93 cohabiting couples who reported
      their interpersonal behavior in interactions with each other during a 20-day
      period. Relationship satisfaction and goal completion were measured at the end of
      the ECR procedure (T2) and approximately 7 months after the ECR (T3). Need
      satisfaction and perceived autonomy support were measured at T2. In both genders,
      higher spin was associated with lower T2 relationship satisfaction. There was
      also a decline in relationship satisfaction from T2 to T3 among men with high
      spin partners. In both genders, higher spin was associated with lower need
      satisfaction, and lower need satisfaction was associated with a decline in
      relationship satisfaction from T2 to T3. In both genders, higher spin was
      associated with lower perceived autonomy support, and lower support was
      associated with decreased progress in goal completion from T2 to T3. The effects
      of spin were independent of the effects of mean levels of behavior. These
      findings extend the understanding of the detrimental consequences of dispersion
      in interpersonal behavior to the disruption of the person's romantic
      relationships.

PMID- 25938701
TI  - From "we" to "me": Group identification enhances perceived personal control with
      consequences for health and well-being.
AB  - There is growing recognition that identification with social groups can protect
      and enhance health and well-being, thereby constituting a kind of "social cure."
      The present research explores the role of control as a novel mediator of the
      relationship between shared group identity and well-being. Five studies provide
      evidence for this process. Group identification predicted significantly greater
      perceived personal control across 47 countries (Study 1), and in groups that had
      experienced success and failure (Study 2). The relationship was observed
      longitudinally (Study 3) and experimentally (Study 4). Manipulated group
      identification also buffered a loss of personal control (Study 5). Across the
      studies, perceived personal control mediated social cure effects in political,
      academic, community, and national groups. The findings reveal that the personal
      benefits of social groups come not only from their ability to make people feel
      good, but also from their ability to make people feel capable and in control of
      their lives.

PMID- 25938702
TI  - Idiosyncratic versus social consensus approaches to personality: Self-view,
      perceived, and peer-view similarity.
AB  - In the current studies, the authors examined how peers influence friendship
      choices through individuals' perceptions of similarity between their own and
      others' Big Five traits. Self-reported and peer-reported data were gathered from
      3 independent samples using longitudinal round-robin designs. Peers' ratings of
      how similar 2 persons appeared in extraversion and agreeableness predicted
      friendship formation likelihood between these 2 persons in all samples. This
      association was mediated by perceived similarity. Furthermore, another mediation
      effect was found for similarity in interaction style: Persons who were viewed by
      peers as having similar extraversion and agreeableness levels became more similar
      in interaction styles. Thus, the current studies indicate that extraversion and
      agreeableness influence the emergence of social relationships through
      intrapersonal perceptions of similarity and interpersonal social interactions. We
      encourage researchers to look at specific similarity effects that influence
      interpersonal and intrapersonal processes to understand how relationships are
      formed.

PMID- 25938703
TI  - Thin slices of child personality: Perceptual, situational, and behavioral
      contributions.
AB  - The present study examined whether thin-slice ratings of child personality serve
      as a resource-efficient and theoretically valid measurement of child personality
      traits. We extended theoretical work on the observability, perceptual accuracy,
      and situational consistency of childhood personality traits by examining
      intersource and interjudge agreement, cross-situational consistency, and
      convergent, divergent, and predictive validity of thin-slice ratings. Forty-five
      unacquainted independent coders rated 326 children's (ages 8-12) personality in 1
      of 15 thin-slice behavioral scenarios (i.e., 3 raters per slice, for over 14,000
      independent thin-slice ratings). Mothers, fathers, and children rated children's
      personality, psychopathology, and competence. We found robust evidence for
      correlations between thin-slice and mother/father ratings of child personality,
      within- and across-task consistency of thin-slice ratings, and convergent and
      divergent validity with psychopathology and competence. Surprisingly, thin-slice
      ratings were more consistent across situations in this child sample than
      previously found for adults. Taken together, these results suggest that thin
      slices are a valid and reliable measure to assess child personality, offering a
      useful method of measurement beyond questionnaires, helping to address novel
      questions of personality perception and consistency in childhood.

PMID- 25938704
TI  - Incidence of Concussion During Practice and Games in Youth, High School, and
      Collegiate American Football Players.
AB  - IMPORTANCE: A report by the Institute of Medicine called for comprehensive
      nationwide concussion incidence data across the spectrum of athletes aged 5 to 23
      years. OBJECTIVE: To describe the incidence of concussion in athletes
      participating in youth, high school, and collegiate American football. DESIGN,
      SETTING, AND PARTICIPANTS: Data were collected by athletic trainers at youth,
      high school, and collegiate football practices and games to create multiple
      prospective observational cohorts during the 2012 and 2013 football seasons. Data
      were collected from July 1, 2012, through January 31, 2013, for the 2012 season
      and from July 1, 2013, through January 31, 2014, for the 2013 season. The Youth
      Football Surveillance System included 118 youth football teams, providing 4092
      athlete-seasons. The National Athletic Treatment, Injury and Outcomes Network
      program included 96 secondary school football programs, providing 11 957 athlete
      seasons. The National Collegiate Athletic Association Injury Surveillance Program
      included 24 member institutions, providing 4305 athlete-seasons. EXPOSURES: All
      injuries regardless of severity, including concussions, and athlete exposure
      information were documented by athletic trainers during practices and games. MAIN
      OUTCOMES AND MEASURES: Injury rates, injury rate ratios, risks, risk ratios, and
      95% CIs were calculated. RESULTS: Concussions comprised 9.6%, 4.0%, and 8.0% of
      all injuries reported in the Youth Football Surveillance System; National
      Athletic Treatment, Injury and Outcomes Network; and National Collegiate Athletic
      Association Injury Surveillance Program, respectively. The game concussion rate
      was higher than the practice concussion rate across all 3 competitive levels. The
      game concussion rate for college athletes (3.74 per 1000 athlete exposures) was
      higher than those for high school athletes (injury rate ratio, 1.86; 95% CI, 1.50
      2.31) and youth athletes (injury rate ratio, 1.57; 95% CI, 1.17-2.10). The
      practice concussion rate in college (0.53 per 1000 athlete exposures) was lower
      than that in high school (injury rate ratio, 0.80; 95% CI, 0.67-0.96). Youth
      football had the lowest 1-season concussion risks in 2012 (3.53%) and 2013
      (3.13%). The 1-season concussion risk was highest in high school (9.98%) and
      college (5.54%) in 2012. CONCLUSIONS AND RELEVANCE: Football practices were a
      major source of concussion at all 3 levels of competition. Concussions during
      practice might be mitigated and should prompt an evaluation of technique and head
      impact exposure. Although it is more difficult to change the intensity or
      conditions of a game, many strategies can be used during practice to limit player
      to-player contact and other potentially injurious behaviors.

PMID- 25938705
TI  - All-Solid-State Symmetric Supercapacitor Based on Co3O4 Nanoparticles on
      Vertically Aligned Graphene.
AB  - We have synthesized the hybrid supercapacitor electrode of Co3O4 nanoparticles on
      vertically aligned graphene nanosheets (VAGNs) supported by carbon fabric. The
      VAGN served as an excellent backbone together with the carbon fabric, enhancing
      composites to a high specific capacitance of 3480 F/g, approaching the
      theoretical value (3560 F/g). A highly flexible all-solid-state symmetric
      supercapacitor device was fabricated by two pieces of our Co3O4/VAGN/carbon
      fabric hybrid electrode. The device is suitable for different bending angles and
      delivers a high capacitance (580 F/g), good cycling ability (86.2% capacitance
      retention after 20 000 cycles), high energy density (80 Wh/kg), and high power
      density (20 kW/kg at 27 Wh/kg). These excellent electrochemical performances, as
      a result of the particular structure of VAGN and the flexibility of the carbon
      fabric, suggest that these composites have an enormous potential in energy
      application. 

PMID- 25938706
TI  - TEMPORARY REMOVAL:  A "cough induced" pelvic fracture as the first sign of a
      malignant neoplasm.
AB  - The publisher regrets that this article has been temporarily removed. A
      replacement will appear as soon as possible in which the reason for the removal
      of the article will be specified, or the article will be reinstated.The full
      Elsevier Policy on Article Withdrawal can be found at
      https://www.elsevier.com/about/our-business/policies/article-withdrawal.

PMID- 25938707
TI  - Metal-free catalysts for oxygen reduction reaction.

PMID- 25938708
TI  - Melatonin for sleep disturbance in children with neurodevelopmental disorders:
      prospective observational naturalistic study.
AB  - BACKGROUND: Although melatonin is increasingly used for sleep disturbances in
      children with neurodevelopmental disorders, evidence on effective dose and impact
      on specific types of sleep disturbance is limited. METHOD: We assessed 45
      children (35 males, mean age: 6.3 +/- 1.7 years) with neurodevelopmental
      disorders (n = 29: intellectual disability; n = 9: autism spectrum disorder; n =
      7: attention-deficit/hyperactivity disorder) and sleep disturbances, treated with
      melatonin (mean duration: 326 days) with doses increased according to response.
      RESULTS: Thirty-eight percent of children responded to low (2.5-3 mg), 31% to
      medium (5-6 mg) and 9% to high doses (9-10 mg) of melatonin, with a significant
      increase in total hours of sleep/night, decreased sleep onset delay and decreased
      number of awakenings/night (all: p = 0.001), as measured with sleep diaries. No
      serious adverse events were reported. CONCLUSIONS: Melatonin is generally
      effective and safe in children with neurodevelopmental conditions. Increasing
      above 6 mg/night adds further benefit only in a small percentage of children.

PMID- 25938709
TI  - Can marriage education mitigate the risks associated with premarital
      cohabitation?
AB  - This study tested whether relationship education (i.e., the Prevention and
      Relationship Education Program; PREP) can mitigate the risk of having cohabited
      before making a mutual commitment to marry (i.e., "precommitment cohabitation")
      for marital distress and divorce. Using data from a study of PREP for married
      couples in the U.S. Army (N = 662 couples), we found that there was a significant
      association between precommitment cohabitation and lower marital satisfaction and
      dedication before random assignment to intervention. After intervention, this
      precommitment cohabitation effect was only apparent in the control group.
      Specifically, significant interactions between intervention condition and
      cohabitation history indicated that for the control group, but not the PREP
      group, precommitment cohabitation was associated with lower dedication as well as
      declines in marital satisfaction and increases in negative communication over
      time. Furthermore, those with precommitment cohabitation were more likely to
      divorce by the 2-year follow-up only in the control group; there were no
      differences in divorce based on premarital cohabitation history in the PREP
      group. These findings are discussed in light of current research on cohabitation
      and relationship education; potential implications are also considered.

PMID- 25938710
TI  - Mexican-origin parents' work conditions and adolescents' adjustment.
AB  - Mexican-origin parents' work experiences are a distal extrafamilial context for
      adolescents' adjustment. This 2-wave multiinformant study examined the
      prospective mechanisms linking parents' work conditions (i.e., self-direction,
      work pressure, workplace discrimination) to adolescents' adjustment (i.e.,
      educational expectations, depressive symptoms, risky behavior) across the
      transition to high school drawing on work socialization and spillover models. We
      examined the indirect effects of parental work conditions on adolescent
      adjustment through parents' psychological functioning (i.e., depressive symptoms,
      role overload) and aspects of the parent-adolescent relationship (i.e., parental
      solicitation, parent-adolescent conflict), as well as moderation by adolescent
      gender. Participants were 246 predominantly immigrant, Mexican-origin, 2-parent
      families who participated in home interviews when adolescents were approximately
      13 and 15 years of age. Results supported the positive impact of fathers'
      occupational self-direction on all 3 aspects of adolescents' adjustment through
      decreased father-adolescent conflict, after controlling for family socioeconomic
      status and earner status, and underemployment. Parental work pressure and
      discrimination were indirectly linked to adolescents' adjustment, with different
      mechanisms emerging for mothers and fathers. Adolescents' gender moderated the
      associations between fathers' self-direction and girls' depressive symptoms, and
      fathers' experiences of discrimination and boys' risk behavior. Results suggest
      that Mexican-origin mothers' and fathers' perceptions of work conditions have
      important implications for multiple domains of adolescents' adjustment across the
      transition to high school.

PMID- 25938711
TI  - Disposable diaper use promotes consolidated nighttime sleep and positive mother
      infant interactions in Chinese 6-month-olds.
AB  - The emergence of consolidated nighttime sleep and the formation and maintenance
      of parent-infant relationships are 2 primary developmental achievements of the
      infancy period. Despite the development of a transactional model that links
      parenting behaviors to infant sleep, limited attention has been devoted to
      examining experimental manipulations of infant sleep that may impact the discrete
      parent-infant interactions that may form the foundation for emerging attachment
      relationships. In the present study, infants were randomly assigned to wear high
      absorbency disposable diapers or to continue using traditional low-absorbency
      cloth diapers that necessitate frequent changes and associated disruptions of
      nighttime sleep. Parents reported on infant sleep before and during the 6-week
      experimental manipulation; a subset of infants also wore actigraphs. Parents and
      infants also participated in a parent-infant interaction task both before and
      near the end of the experimental manipulation. Infants who wore cloth diapers
      experienced more frequent sleep disruptions overall as well as a greater number
      of disruptions that did and did not wake the infant from sleep. Infants who wore
      disposable diapers were rated as experiencing more engagement and positive affect
      near the end of the intervention relative to infants who wore cloth diapers;
      mothers of infants who wore disposable diapers were rated as more engaged and
      sensitive near the end of the intervention relative to mothers of infants who
      wore cloth diapers. These findings suggest that the disposable diaper
      manipulation was causally related to characteristics of mother-infant
      interactions that may form the foundation for emerging attachment relationships.

PMID- 25938712
TI  - Immigration and the interplay of parenting, preschool enrollment, and young
      children's academic skills.
AB  - This study tested a conceptual model of the reciprocal relations among parents'
      support for early learning and children's academic skills and preschool
      enrollment. Structural equation modeling of data from 6,250 children (Ages 2 to
      5) and parents in the nationally representative Early Childhood Longitudinal
      Study-Birth Cohort revealed that parental support for early learning was
      associated with gains in children's academic skills, which, in turn, were
      associated with their likelihood of preschool attendance. Preschool experience
      then was associated with further gains in children's early academic competencies,
      which were then associated with increased parental support. These patterns varied
      by parents' nativity status. Specifically, foreign-born parents' support for
      early learning was directly linked with preschool enrollment, and the association
      between the academic skills of children and parental support was also stronger
      for foreign-born parents. These immigration-related patterns were primarily
      driven by immigrant families who originated from Latin America, rather than Asia,
      and did not vary by immigrants' socioeconomic circumstances. Together, these
      results underscore the value of considering the synergistic relations between the
      home and school systems, as well as "child effects" and population diversity, in
      developmental research.

PMID- 25938713
TI  - Revealing Surface States in In-Doped SnTe Nanoplates with Low Bulk Mobility.
AB  - Indium (In) doping in topological crystalline insulator SnTe induces
      superconductivity, making In-doped SnTe a candidate for a topological
      superconductor. SnTe nanostructures offer well-defined nanoscale morphology and
      high surface-to-volume ratios to enhance surface effects. Here, we study In-doped
      SnTe nanoplates, In(x)Sn(1-x)Te, with x ranging from 0 to 0.1 and show they
      superconduct. More importantly, we show that In doping reduces the bulk mobility
      of In(x)Sn(1-x)Te such that the surface states are revealed in magnetotransport
      despite the high bulk carrier density. This is manifested by two-dimensional
      linear magnetoresistance in high magnetic fields, which is independent of
      temperature up to 10 K. Aging experiments show that the linear magnetoresistance
      is sensitive to ambient conditions, further confirming its surface origin. We
      also show that the weak antilocalization observed in In(x)Sn(1-x)Te nanoplates is
      a bulk effect. Thus, we show that nanostructures and reducing the bulk mobility
      are effective strategies to reveal the surface states and test for topological
      superconductors.

PMID- 25938714
TI  - Histone H3.3 is required for endogenous retroviral element silencing in embryonic
      stem cells.
AB  - Transposable elements comprise roughly 40% of mammalian genomes. They have an
      active role in genetic variation, adaptation and evolution through the
      duplication or deletion of genes or their regulatory elements, and transposable
      elements themselves can act as alternative promoters for nearby genes, resulting
      in non-canonical regulation of transcription. However, transposable element
      activity can lead to detrimental genome instability, and hosts have evolved
      mechanisms to silence transposable element mobility appropriately. Recent studies
      have demonstrated that a subset of transposable elements, endogenous retroviral
      elements (ERVs) containing long terminal repeats (LTRs), are silenced through
      trimethylation of histone H3 on lysine 9 (H3K9me3) by ESET (also known as SETDB1
      or KMT1E) and a co-repressor complex containing KRAB-associated protein 1 (KAP1;
      also known as TRIM28) in mouse embryonic stem cells. Here we show that the
      replacement histone variant H3.3 is enriched at class I and class II ERVs,
      notably those of the early transposon (ETn)/MusD family and intracisternal A-type
      particles (IAPs). Deposition at a subset of these elements is dependent upon the
      H3.3 chaperone complex containing alpha-thalassaemia/mental retardation syndrome
      X-linked (ATRX) and death-domain-associated protein (DAXX). We demonstrate that
      recruitment of DAXX, H3.3 and KAP1 to ERVs is co-dependent and occurs upstream of
      ESET, linking H3.3 to ERV-associated H3K9me3. Importantly, H3K9me3 is reduced at
      ERVs upon H3.3 deletion, resulting in derepression and dysregulation of adjacent,
      endogenous genes, along with increased retrotransposition of IAPs. Our study
      identifies a unique heterochromatin state marked by the presence of both H3.3 and
      H3K9me3, and establishes an important role for H3.3 in control of ERV
      retrotransposition in embryonic stem cells. 

PMID- 25938715
TI  - Synthesis and applications of RNAs with position-selective labelling and mosaic
      composition.
AB  - Knowledge of the structure and dynamics of RNA molecules is critical to
      understanding their many biological functions. Furthermore, synthetic RNAs have
      applications as therapeutics and molecular sensors. Both research and
      technological applications of RNA would be dramatically enhanced by methods that
      enable incorporation of modified or labelled nucleotides into specifically
      designated positions or regions of RNA. However, the synthesis of tens of
      milligrams of such RNAs using existing methods has been impossible. Here we
      develop a hybrid solid-liquid phase transcription method and automated robotic
      platform for the synthesis of RNAs with position-selective labelling. We
      demonstrate its use by successfully preparing various isotope- or fluorescently
      labelled versions of the 71-nucleotide aptamer domain of an adenine riboswitch
      for nuclear magnetic resonance spectroscopy or single-molecule Forster resonance
      energy transfer, respectively. Those RNAs include molecules that were selectively
      isotope-labelled in specific loops, linkers, a helix, several discrete positions,
      or a single internal position, as well as RNA molecules that were fluorescently
      labelled in and near kissing loops. These selectively labelled RNAs have the same
      fold as those transcribed using conventional methods, but they greatly simplify
      the interpretation of NMR spectra. The single-position isotope- and fluorescently
      labelled RNA samples reveal multiple conformational states of the adenine
      riboswitch. Lastly, we describe a robotic platform and the operation that
      automates this technology. Our selective labelling method may be useful for
      studying RNA structure and dynamics and for making RNA sensors for a variety of
      applications including cell-biological studies, substance detection, and disease
      diagnostics. 

PMID- 25938716
TI  - Epicardial regeneration is guided by cardiac outflow tract and Hedgehog
      signalling.
AB  - In response to cardiac damage, a mesothelial tissue layer enveloping the heart
      called the epicardium is activated to proliferate and accumulate at the injury
      site. Recent studies have implicated the epicardium in multiple aspects of
      cardiac repair: as a source of paracrine signals for cardiomyocyte survival or
      proliferation; a supply of perivascular cells and possibly other cell types such
      as cardiomyocytes; and as a mediator of inflammation. However, the biology and
      dynamism of the adult epicardium is poorly understood. To investigate this, we
      created a transgenic line to ablate the epicardial cell population in adult
      zebrafish. Here we find that genetic depletion of the epicardium after myocardial
      loss inhibits cardiomyocyte proliferation and delays muscle regeneration. The
      epicardium vigorously regenerates after its ablation, through proliferation and
      migration of spared epicardial cells as a sheet to cover the exposed ventricular
      surface in a wave from the chamber base towards its apex. By reconstituting
      epicardial regeneration ex vivo, we show that extirpation of the bulbous
      arteriosus-a distinct, smooth-muscle-rich tissue structure that distributes
      outflow from the ventricle-prevents epicardial regeneration. Conversely,
      experimental repositioning of the bulbous arteriosus by tissue recombination
      initiates epicardial regeneration and can govern its direction. Hedgehog (Hh)
      ligand is expressed in the bulbous arteriosus, and treatment with a Hh signalling
      antagonist arrests epicardial regeneration and blunts the epicardial response to
      muscle injury. Transplantation of Sonic hedgehog (Shh)-soaked beads at the
      ventricular base stimulates epicardial regeneration after bulbous arteriosus
      removal, indicating that Hh signalling can substitute for the influence of the
      outflow tract. Thus, the ventricular epicardium has pronounced regenerative
      capacity, regulated by the neighbouring cardiac outflow tract and Hh signalling.
      These findings extend our understanding of tissue interactions during
      regeneration and have implications for mobilizing epicardial cells for
      therapeutic heart repair. 

PMID- 25938717
TI  - Using Adeno-associated Virus as a Tool to Study Retinal Barriers in Disease.
AB  - Muller cells are the principal glial cells of the retina. Their end-feet form the
      limits of the retina at the outer and inner limiting membranes (ILM), and in
      conjunction with astrocytes, pericytes and endothelial cells they establish the
      blood-retinal barrier (BRB). BRB limits material transport between the
      bloodstream and the retina while the ILM acts as a basement membrane that defines
      histologically the border between the retina and the vitreous cavity. Labeling
      Muller cells is particularly relevant to study the physical state of the retinal
      barriers, as these cells are an integral part of the BRB and ILM. Both BRB and
      ILM are frequently altered in retinal disease and are responsible for disease
      symptoms. There are several well-established methods to study the integrity of
      the BRB, such as the Evans blue assay or fluorescein angiography. However these
      methods do not provide information on the extent of BRB permeability to larger
      molecules, in nanometer range. Furthermore, they do not provide information on
      the state of other retinal barriers such as the ILM. To study BRB permeability
      alongside retinal ILM, we used an AAV based method that provides information on
      permeability of BRB to larger molecules while indicating the state of the ILM and
      extracellular matrix proteins in disease states. Two AAV variants are useful for
      such study: AAV5 and ShH10. AAV5 has a natural tropism for photoreceptors but it
      cannot get across to the outer retina when administered into the vitreous when
      the ILM is intact (i.e., in wild-type retinas). ShH10 has a strong tropism
      towards glial cells and will selectively label Muller glia in both healthy and
      diseased retinas. ShH10 provides more efficient gene delivery in retinas where
      ILM is compromised. These viral tools coupled with immunohistochemistry and blood
      DNA analysis shed light onto the state of retinal barriers in disease. 

PMID- 25938718
TI  - Dynamic contrast enhanced magnetic resonance imaging of an orthotopic pancreatic
      cancer mouse model.
AB  - Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) has been limitedly
      used for orthotopic pancreatic tumor xenografts due to severe respiratory motion
      artifact in the abdominal area. Orthotopic tumor models offer advantages over
      subcutaneous ones, because those can reflect the primary tumor microenvironment
      affecting blood supply, neovascularization, and tumor cell invasion. We have
      recently established a protocol of DCE-MRI of orthotopic pancreatic tumor
      xenografts in mouse models by securing tumors with an orthogonally bent plastic
      board to prevent motion transfer from the chest region during imaging. The
      pressure by this board was localized on the abdominal area, and has not resulted
      in respiratory difficulty of the animals. This article demonstrates the detailed
      procedure of orthotopic pancreatic tumor modeling using small animals and DCE-MRI
      of the tumor xenografts. Quantification method of pharmacokinetic parameters in
      DCE-MRI is also introduced. The procedure described in this article will assist
      investigators to apply DCE-MRI for orthotopic gastrointestinal cancer mouse
      models. 

PMID- 25938720
TI  - Immunohistochemistry and multiple labeling with antibodies from the same host
      species to study adult hippocampal neurogenesis.
AB  - Adult neurogenesis is a highly regulated, multi-stage process in which new
      neurons are generated from an activated neural stem cell via increasingly
      committed intermediate progenitor subtypes. Each of these subtypes expresses a
      set of specific molecular markers that, together with specific morphological
      criteria, can be used for their identification. Typically, immunofluorescent
      techniques are applied involving subtype-specific antibodies in combination with
      exo- or endogenous proliferation markers. We herein describe immunolabeling
      methods for the detection and quantification of all stages of adult hippocampal
      neurogenesis. These comprise the application of thymidine analogs, transcardial
      perfusion, tissue processing, heat-induced epitope retrieval, ABC
      immunohistochemistry, multiple indirect immunofluorescence, confocal microscopy
      and cell quantification. Furthermore we present a sequential multiple
      immunofluorescence protocol which circumvents problems usually arising from the
      need of using primary antibodies raised in the same host species. It allows an
      accurate identification of all hippocampal progenitor subtypes together with a
      proliferation marker within a single section. These techniques are a powerful
      tool to study the regulation of different progenitor subtypes in parallel, their
      involvement in brain pathologies and their role in specific brain functions.

PMID- 25938721
TI  - Protecting the turf: The effect of territorial marking on others' creativity.
AB  - Territorial marking allows people to communicate that a territory has been
      claimed. Across 2 studies, we examine the impact of territorial marking of one's
      ideas on others' invited creativity when asked to provide feedback. Integrating
      research on territoriality and self-construal, we examine the effect of control
      oriented marking on invited creativity (Study 1), and the extent to which an
      independent versus interdependent self-construal moderates this effect (Study 2).
      Results of Study 1 demonstrate that the use of control-oriented marking to
      communicate a territorial claim over one's ideas inhibits invited creativity, and
      this effect is mediated by intrinsic motivation. Also consistent with our
      hypotheses, the results of Study 2 show that self-construal moderates the effect
      of control-oriented marking on others' intrinsic motivation and creativity.
      Marking diminishes invited creativity among people with an independent self
      construal but serves to enhance the creativity of those with an interdependent
      self-construal. Consistent with Study 1, intrinsic motivation mediates this
      moderated effect. Our results highlight the important but heretofore understudied
      role of territoriality in affecting others' creativity as well as the role of
      independent versus interdependent self-construal in shaping this effect.

PMID- 25938719
TI  - Characterization of an IL-12 p40/p35 Truncated Fusion Protein That can Inhibit
      the Action of IL-12.
AB  - Interleukin-12 (IL-12), a potent inducer of interferon gamma (IFNgamma), is a
      heterodimeric protein consisting of p40 and p35 subunits whose expression is
      regulated independently. IL-12 is part of a cytokine family (currently consisting
      of IL-12, IL-23, IL-27, and IL-35) that can have profoundly different immunologic
      effects, despite sharing subunits. In constructing a single-chain fusion of p40
      and p35, we discovered an insert corresponding to an intron in the gene encoding
      the p35 subunit that would result in a truncated form of p35 if translated. To
      test its possible role, we constructed, expressed, and analyzed fusions of p40
      with the full-length or the truncated form of p35. The fusion protein containing
      the truncated p35 did not stimulate the proliferation of the IL-12-responsive
      cell line CTLL-2 nor did it induce IFNgamma or the chemokine IFNgamma-inducible
      protein 10 (IP-10, CXCL10) or monokine induced by IFNgamma (MIG, CXCL9) from
      spleen cells. In striking contrast, the full-length IL-12 p40/p35 fusion induced
      robust responses in both assays. Moreover, the truncated IL-12 fusion protein
      inhibited the action of the full-length IL-12 p40/p35 fusion in the proliferation
      assay and also blocked the induction of IFNgamma. These findings raise the
      possibility that alternative splicing may provide an additional regulatory
      mechanism for IL-12. 

PMID- 25938722
TI  - Structural interdependence in teams: An integrative framework and meta-analysis.
AB  - Although interdependence is a central aspect of team design, there has been a
      lack of clarity regarding the meaning and impact of different forms of
      interdependence. To provide theoretical clarity and to advance research on team
      interdependence, we develop an organizing, conceptual framework of
      interdependence in teams and test it using meta-analysis. We first review and tie
      together different conceptualizations of interdependence in the literature and
      illustrate how they converge around 2 major constructs: task interdependence and
      outcome interdependence. After providing integrative definitions of these forms
      of interdependence, as well as subdimensions, we then explore the relative
      effects of task and outcome interdependence on team functioning and performance.
      Specifically, we propose a pattern of differential effects in which task
      interdependence is primarily associated with team performance through its effects
      on task-focused team functioning (i.e., transition/action processes, collective
      efficacy), whereas outcome interdependence is primarily associated with team
      performance through its effects on relational team functioning (i.e.,
      interpersonal processes, cohesion). We test these differential effects using a
      meta-analytic database of 107 independent samples and 7,563 teams. The meta
      analytic path model provides strong support for our hypotheses. Implications and
      future directions for the study of interdependence in work teams are discussed.

PMID- 25938723
TI  - Density functional theory analysis of the impact of steric interaction on the
      function of switchable polarity solvents.
AB  - A density functional theory (DFT) analysis has been performed to explore the
      impact of steric interactions on the function of switchable polarity solvents
      (SPS) and their implications on a quantitative structure-activity relationship
      (QSAR) model previously proposed for SPS. An X-ray crystal structure of the N,N
      dimethylcyclohexylammonium bicarbonate (Hdmcha) salt has been solved as an
      asymmetric unit containing two cation/anion pairs, with a hydrogen bonding
      interaction observed between the bicarbonate anions, as well as between the
      cation and anion in each pair. DFT calculations provide an optimized structure of
      Hdmcha that closely resembles experimental data and reproduces the cation/anion
      interaction with the inclusion of a dielectric field. Relaxed potential energy
      surface (PES) scans have been performed on Hdmcha-based computational model
      compounds, differing in the size of functional group bonded to the nitrogen
      center, to assess the steric impact of the group on the relative energy and
      structural properties of the compound. Results suggest that both the length and
      amount of branching associated with the substituent impact the energetic
      limitations on rotation of the group along the N-R bond and NC-R bond, and
      disrupt the energy minimized position of the hydrogen bonded bicarbonate group.
      The largest interaction resulted from functional groups that featured five bonds
      between the ammonium proton and a proton on a functional group with the freedom
      of rotation to form a pseudo six membered ring which included both protons. 

PMID- 25938724
TI  - Gold embedded maghemite hybrid nanowires and their gas sensing properties.
AB  - Well-defined gold embedded maghemite hybrid nanowires are synthesized, and their
      structures are fully characterized. They are composed of porous gamma-Fe2O3
      shells and embedded gold nanoparticles (3-10 nm), which is novel and very
      different from the conventional "surface decoration" configuration. These hybrid
      nanowires are produced by the de-alloying of Au-Fe alloy nanowires and subsequent
      heat treatment. The reaction mechanism is proposed and validated. The results of
      X-ray diffraction, scanning electron microscopy, transmission electron
      microscopy, and thermogravimetry techniques prove consistently that the Fe
      composition of Au-Fe alloy nanowires change to gamma-FeOOH first and then to
      gamma-Fe2O3. The embedded gold particles are help to enhance the gas response
      properties of the hybrid nanowires, which is attributed to the nano open-circuit
      Schottky junctions between gamma-Fe2O3 and the Au nanoparticles. The gas sensing
      experiment data with high repeatability demonstrate that these hybrid nanowires
      are excellent sensing materials, especially for ethanol, and have shown both high
      selectivity and high sensitivity. 

PMID- 25938725
TI  - Effects of Weak Surface Modification on Co/SiO2 Catalyst for Fischer-Tropsch
      Reaction.
AB  - A weak surface modification is applied to Co/SiO2 catalyst by hydrothermal
      treatment at 180 degrees C for 5 h. Aluminum is introduced to Co/SiO2 catalysts
      during the surface modification. The effects of surface modification on Co/SiO2
      catalyst are studied by changing the operating sequences of surface modification
      and cobalt impregnation in the catalyst preparation. Surface modification before
      cobalt impregnation makes Co3O4 particle small and dispersed into the deep part
      of enlarged pore in SiO2, while surface modification after cobalt impregnation
      does not obviously change the particle size of Co3O4. The improved amplitude of
      catalytic activity is similar for the two kinds of catalysts, but they are
      benefited from different factors. The content of iso-hydrocarbons in the products
      is increased by the surface modifications. 

PMID- 25938726
TI  - The brain's default mode network.
AB  - The brain's default mode network consists of discrete, bilateral and symmetrical
      cortical areas, in the medial and lateral parietal, medial prefrontal, and medial
      and lateral temporal cortices of the human, nonhuman primate, cat, and rodent
      brains. Its discovery was an unexpected consequence of brain-imaging studies
      first performed with positron emission tomography in which various novel,
      attention-demanding, and non-self-referential tasks were compared with quiet
      repose either with eyes closed or with simple visual fixation. The default mode
      network consistently decreases its activity when compared with activity during
      these relaxed nontask states. The discovery of the default mode network reignited
      a longstanding interest in the significance of the brain's ongoing or intrinsic
      activity. Presently, studies of the brain's intrinsic activity, popularly
      referred to as resting-state studies, have come to play a major role in studies
      of the human brain in health and disease. The brain's default mode network plays
      a central role in this work. 

PMID- 25938727
TI  - Cell types, circuits, and receptive fields in the mouse visual cortex.
AB  - Over the past decade, the mouse has emerged as an important model system for
      studying cortical function, owing to the advent of powerful tools that can record
      and manipulate neural activity in intact neural circuits. This advance has been
      particularly prominent in the visual cortex, where studies in the mouse have
      begun to bridge the gap between cortical structure and function, allowing
      investigators to determine the circuits that underlie specific visual
      computations. This review describes the advances in our understanding of the
      mouse visual cortex, including neural coding, the role of different cell types,
      and links between vision and behavior, and discusses how recent findings and new
      approaches can guide future studies. 

PMID- 25938728
TI  - In search of a human self-regulation system.
AB  - The capacity for self-regulation allows people to control their thoughts,
      behaviors, emotions, and desires. In spite of this impressive ability, failures
      of self-regulation are common and contribute to numerous societal problems, from
      obesity to drug addiction. Such failures frequently occur following exposure to
      highly tempting cues, during negative moods, or after self-regulatory resources
      have been depleted. Here we review the available neuroscientific evidence
      regarding self-regulation and its failures. At its core, self-regulation involves
      a critical balance between the strength of an impulse and an individual's ability
      to inhibit the desired behavior. Although neuroimaging and patient studies
      provide consistent evidence regarding the reward aspects of impulses and desires,
      the neural mechanisms that underlie the capacity for control have eluded
      consensus, with various executive control regions implicated in different
      studies. We outline the necessary properties for a self-regulation control system
      and suggest that the use of resting-state functional connectivity analyses may be
      useful for understanding how people regulate their behavior and why they
      sometimes fail in their attempts. 

PMID- 25938730
TI  - Nondeterministic computational fluid dynamics modeling of Escherichia coli
      inactivation by peracetic acid in municipal wastewater contact tanks.
AB  - Wastewater disinfection processes are typically designed according to heuristics
      derived from batch experiments in which the interaction among wastewater quality,
      reactor hydraulics, and inactivation kinetics is often neglected. In this paper,
      a computational fluid dynamics (CFD) study was conducted in a nondeterministic
      (ND) modeling framework to predict the Escherichia coli inactivation by peracetic
      acid (PAA) in municipal contact tanks fed by secondary settled wastewater
      effluent. The extent and variability associated with the observed inactivation
      kinetics were both satisfactorily predicted by the stochastic inactivation model
      at a 95% confidence level. Moreover, it was found that (a) the process
      variability induced by reactor hydraulics is negligible when compared to the one
      caused by inactivation kinetics, (b) the PAA dose required for meeting
      regulations is dictated equally by the fixed limit of the microbial concentration
      as well as its probability of occurrence, and (c) neglecting the probability of
      occurrence during process sizing could lead to an underestimation of the PAA dose
      required by as much as 100%. Finally, the ND-CFD model was used to generate
      sizing information in the form of probabilistic disinfection curves relating E.
      coli inactivation and probability of occurrence with the average PAA dose and PAA
      residual concentration at the outlet of the contact tank.

PMID- 25938731
TI  - Oil spill dispersants: boon or bane?
AB  - Dispersants provide a reliable large-scale response to catastrophic oil spills
      that can be used when the preferable option of recapturing the oil cannot be
      achieved. By allowing even mild wave action to disperse floating oil into tiny
      droplets (<70 MUm) in the water column, seabirds, reptiles, and mammals are
      protected from lethal oiling at the surface, and microbial biodegradation is
      dramatically increased. Recent work has clarified how dramatic this increase is
      likely to be: beached oil has an environmental residence of years, whereas
      dispersed oil has a half-life of weeks. Oil spill response operations endorse the
      concept of net environmental benefit, that any environmental costs imposed by a
      response technique must be outweighed by the likely benefits. This critical
      review discusses the potential environmental debits and credits from dispersant
      use and concludes that, in most cases, the potential environmental costs of
      adding these chemicals to a polluted area are likely outweighed by the much
      shorter residence time, and hence integrated environmental impact, of the spilled
      oil in the environment. 

PMID- 25938729
TI  - Chemosensory receptor specificity and regulation.
AB  - The senses provide a means by which data on the physical and chemical properties
      of the environment may be collected and meaningfully interpreted. Sensation
      begins at the periphery, where a multitude of different sensory cell types are
      activated by environmental stimuli as different as photons and odorant molecules.
      Stimulus sensitivity is due to expression of different cell surface sensory
      receptors, and therefore the receptive field of each sense is defined by the
      aggregate of expressed receptors in each sensory tissue. Here, we review current
      understanding on patterns of expression and modes of regulation of sensory
      receptors. 

PMID- 25938732
TI  - Human transport protein carrier for controlled photoactivation of antitumor
      prodrug and real-time intracellular tumor imaging.
AB  - Current anticancer chemotherapy often suffers from poor tumor selectivity and
      serious drug resistance. Proper vectors for targeted delivery and controlled drug
      release play crucial roles in improving the therapeutic selectivity to tumor
      areas and also overcoming the resistance of cancer cells. In this work, we
      developed a novel human serum albumin (HSA) protein-based nanocarrier system,
      which combines the photoactivatable Pt(IV) antitumor prodrug for realizing the
      controlled release and fluorescent light-up probe for evaluations of drug action
      and efficacy. The constructed Pt(IV)-probe@HSA platform can be locally activated
      by light irradiation to release the active Pt species, which results in enhanced
      cell death at both drug-sensitive A2780 and cisplatin-resistant A2780cis cell
      lines when compared to the free prodrug molecules. Simultaneously, the
      cytotoxicity caused by light controlled drug release would further lead to the
      cellular apoptosis and trigger the activation of caspases 3, one crucial protease
      enzyme in apoptotic process, which could cleave the recognition peptide moiety
      (DEVD) with a flanking fluorescent resonance energy transfer (FRET) pair
      containing near-infrared (NIR) fluorophore Cy5 and quencher Qsy21 on the HSA
      nanocarrier surface. The turn-on fluorescence in response to caspase-3 could be
      assessed by fluorescence microscopy and flow cytometry analysis. Our results
      supported the hypothesis that such a unique design may present a successful
      platform for multiple roles: (i) a biocompatible protein-based nanocarrier for
      drug delivery, (ii) the controlled drug release with strengthened therapeutic
      effects, (iii) real-time monitoring of antitumor drug efficacy at the earlier
      stage. 

PMID- 25938733
TI  - Antioxidation improves in puberty in normal weight and obese boys, in positive
      association with exercise-stimulated growth hormone secretion.
AB  - BACKGROUND: Oxidative stress is associated with obesity while the evidence for
      the role of GH in pro- and antioxidation is inconclusive. This study investigates
      the relationships between growth hormone (GH), pro- and antioxidation in relation
      to obesity and puberty before and after an acute bout of exercise. METHODS: In
      this case-control study, 76 healthy normal-weight and obese, prepubertal and
      pubertal boys underwent a blood sampling before and immediately after an aerobic
      exercise bout until exhaustion at 70% maximal oxygen consumption. Markers of
      prooxidation (thiobarbituric acid reactive substances (TBARS) and protein
      carbonyls (PCs)) and antioxidation (glutathione (GSH), oxidized glutathione
      disulfide (GSSG), GSH/GSSG ratio, glutathione peroxidase (GPX), catalase, and
      total antioxidant capacity (TAC)) and hormones (GH, insulin-like growth factor
      (IGF)-1, IGF-BP-3, luteinizing hormone, follicle-stimulating hormone, and
      testosterone) were measured. RESULTS: Baseline and postexercise TBARS and PCs
      were greater, while baseline GSH, GSH/GSSG ratio, GPX, and TAC were lower in
      obese than that in normal-weight participants. In all participants, waist was the
      best negative and positive predictor for postexercise GPX and TBARS,
      respectively. Baseline TAC was greater in pubertal than that in pre-pubertal
      participants. In all participants, baseline GH was the best negative predictor
      for postexercise PCs. Significant positive linear correlation exists between the
      exercise-associated GH, and GSSG increases in pubertal normal-weight boys.
      CONCLUSIONS: Higher prooxidation and lower antioxidation were observed in obese
      boys, while antioxidation improves with puberty and postexercise, paralleling GH
      accentuated secretion.

PMID- 25938734
TI  - Toll-like receptor 4-mediated immune stress in pregnant rats activates STAT3 in
      the fetal brain: role of interleukin-6.
AB  - BACKGROUND: Prenatal exposure to pathogens induces long lasting effect on brain
      function and plasticity. It is unclear how maternal immune stress impacts fetal
      brain development. Immune challenged pregnant rats induce the production of
      inflammatory cytokines including tumor necrosis factor (TNF)alpha, interleukin
      (IL)1beta, and IL-6. IL-6 crosses the placenta but its mechanism of action on
      fetal brain is unclear. METHODS: Gestation day 15 (GD15) rats were given a single
      injection of lipopolysaccharide (LPS) (100 ug/kg) in the presence or the absence
      of an IL-6 neutralizing antibody (IL-6Ab, 10 ug/kg). The activation of the
      intracellular signal of IL-6; signal transducer and activator of transcription
      (STAT3) and levels of glucocorticoids (GCs) were monitored in fetal brains.
      RESULTS: LPS administration to GD15 rats significantly increased the
      phosphorylation levels of STAT3 in fetal brains. Such activation was blunted by
      IL-6Ab. LPS induced a significant rise in GCs in the plasma of dams but not in
      fetal brains. IL-6Ab significantly reduced LPS-induced GCs in maternal plasma.
      CONCLUSION: Toll-like receptor 4 (TLR4)-induced activation of the maternal innate
      immune system affects fetal brains likely via the mobilization of IL-6/STAT3
      pathway. In contrast, TLR4-stimulated maternal GCs release is less likely to play
      a significant role in fetal brain development.

PMID- 25938735
TI  - Dietary aflatoxin-induced stunting in a novel rat model: evidence for toxin
      induced liver injury and hepatic growth hormone resistance.
AB  - BACKGROUND: Despite a strong statistical correlation between dietary aflatoxin B1
      (AFB1)-exposure and childhood stunting, the causal mechanism remains speculative.
      This issue is important because of emerging interest in reduction of human
      aflatoxin exposure to diminish the prevalence and complications of stunting.
      Pediatric liver diseases cause growth impairment, and AFB1 is hepatotoxic. Thus,
      liver injury might mediate AFB1-associated growth impairment. We have developed a
      rat model of dietary AFB1-induced stunting to investigate these questions.
      METHODS: Newly-weaned rats were given AFB1-supplemented- or control-diets from
      age 3-9 wk, and then euthanized for serum- and tissue-collection. Food intake and
      weight were serially assessed, with tibial-length determined at the experimental
      endpoint. Serum AFB1-adducts, hepatic gene and protein expression, and liver
      injury markers were quantified using established methodologies. RESULTS: AFB1
      albumin adducts correlated with dietary toxin contamination, but such
      contamination did not affect food consumption. AFB1-exposed animals exhibited
      dose-dependent wasting and stunting, liver pathology, and suppression of hepatic
      targets of growth hormone (GH) signaling, but did not display increased
      mortality. CONCLUSION: These data establish toxin-dependent liver injury and
      hepatic GH-resistance as candidate mechanisms by which AFB1-exposure causes
      growth impairment in this mammalian model. Interrogation of modifiers of stunting
      using this model could guide interventions in at-risk and affected children.

PMID- 25938736
TI  - Early decreased plasma levels of factor B and C5a are important biomarkers in
      children with Kawasaki disease.
AB  - BACKGROUND: The mechanisms underpinning Kawasaki disease (KD) are incompletely
      understood. There is an unmet need for specific biomarkers for the early
      diagnosis of KD. METHODS: Eighty-five KD patients suffering from acute-phase and
      subacute-phase KD, 40 healthy children, and 40 febrile children comprised the
      study cohort. An enzyme-linked immunosorbent assay was used to measure plasma
      levels of C1q, C1q-circulating immune complex (C1q-CIC), mannan-binding lectin
      associated serine protease (MASP)-1, factor B, C4d, C3d, C5a, C5b-9 and CD59.
      RESULTS: Plasma concentrations of factor B and C5a in the acute phase were lower
      than those in healthy and febrile control groups (all P < 0.05). Compared with
      acute-phase KD patients, plasma concentrations of C1q, factor B, and C3d in KD
      patients were increased significantly (P < 0.05), but those of C4d, MASP-1 and
      CD59 decreased significantly (P < 0.05), in patients with sub-acute KD.
      CONCLUSION: These data suggest that more than one pathway in the complement
      system is activated in KD. Importantly, decreased plasma concentrations of factor
      B and C5a in the acute phase (6-10 d) could be employed as biomarkers for the
      early diagnosis of KD.

PMID- 25938737
TI  - Behavioral Phenotyping of Murine Disease Models with the Integrated Behavioral
      Station (INBEST).
AB  - Due to rapid advances in genetic engineering, small rodents have become the
      preferred subjects in many disciplines of biomedical research. In studies of
      chronic CNS disorders, there is an increasing demand for murine models with high
      validity at the behavioral level. However, multiple pathogenic mechanisms and
      complex functional deficits often impose challenges to reliably measure and
      interpret behavior of chronically sick mice. Therefore, the assessment of
      peripheral pathology and a behavioral profile at several time points using a
      battery of tests are required. Video-tracking, behavioral spectroscopy, and
      remote acquisition of physiological measures are emerging technologies that allow
      for comprehensive, accurate, and unbiased behavioral analysis in a home-base-like
      setting. This report describes a refined phenotyping protocol, which includes a
      custom-made monitoring apparatus (Integrated Behavioral Station, INBEST) that
      focuses on prolonged measurements of basic functional outputs, such as
      spontaneous activity, food/water intake and motivated behavior in a relatively
      stress-free environment. Technical and conceptual improvements in INBEST design
      may further promote reproducibility and standardization of behavioral studies. 

PMID- 25938738
TI  - Tailoring precursors for deposition: synthesis, structure, and thermal studies of
      cyclopentadienylcopper(i) isocyanide complexes.
AB  - We report here the synthesis and characterization of a family of copper(I) metal
      precursors based around cyclopentadienyl and isocyanide ligands. The molecular
      structures of several cyclopentadienylcopper(I) isocyanide complexes have been
      unambiguously determined by single-crystal X-ray diffraction analysis.
      Thermogravimetric analysis of the complexes highlighted the isopropyl isocyanide
      complex [(eta(5)-C5H5)Cu(CN(i)Pr)] (2a) and the tert-butyl isocyanide complex
      [(eta(5)-C5H5)Cu(CN(t)Bu)] (2b) as possible copper metal chemical vapor
      deposition (CVD) precursors. Further modification of the precursors with
      variation of the substituents on the cyclopentadienyl ligand system (varying
      between H, Me, Et, and (i)Pr) has allowed the affect that these changes would
      have on features such as stability, volatility, and decomposition to be
      investigated. As part of this study, the vapor pressures of the complexes 2b,
      [(eta(5)-MeC5H4)Cu(CN(t)Bu)] (3b), [(eta(5)-EtC5H4)Cu(CN(t)Bu)] (4b), and
      [(eta(5)-(i)PrC5H4)Cu(CN(t)Bu)] (5b) over a 40-65  degrees C temperature range
      have been determined. Low-pressure chemical vapor deposition (LP-CVD) was
      employed using precursors 2a and 2b to synthesize thin films of metallic copper
      on silicon, gold, and platinum substrates under a H2 atmosphere. Analysis of the
      thin films deposited onto both silicon and gold substrates at substrate
      temperatures of 180 and 300  degrees C by scanning electron microscopy and atomic
      force microscopy reveals temperature-dependent growth features: Films grown at
      300  degrees C are continuous and pinhole-free, whereas films grown at 180 
      degrees C consist of highly crystalline nanoparticles. In contrast, deposition
      onto platinum substrates at 180  degrees C shows a high degree of surface
      coverage with the formation of high-density, continuous, and pinhole-free thin
      films. Powder X-ray diffraction and X-ray photoelectron spectroscopy (XPS) both
      show the films to be high-purity metallic copper. 

PMID- 25938739
TI  - Palladium-catalyzed regioselective domino cyclization of cyclohexadienones.
AB  - A mild and efficient Pd-catalyzed arylative domino carbocyclization of
      cyclohexadienone-containing 1,6-enynes is described. The reaction tolerates a
      variety of functionalized boronic acids to afford a cis-fused bicyclic framework
      containing an alpha,beta-unsaturated ketone with excellent regio- and
      diastereoselectivity in good yields. The tandem process proceeds with beta
      arylation of propargylic ether followed by conjugate addition of a vinyl
      palladium intermediate and subsequent protonolysis of a palladium enolate. 

PMID- 25938740
TI  - In-Hospital Stroke: Hidden in Plain Sight.

PMID- 25938741
TI  - Grin1 deletion in CRF neurons sex-dependently enhances fear, sociability, and
      social stress responsivity.
AB  - The corticotropin releasing factor (CRF) system plays a critical role in
      responses to stressful stimuli, and is expressed in many areas of the brain
      involved in processing fear, anxiety, and social behaviors. To better understand
      the mechanisms by which the CRF system modulates responses to stressful events
      and social stimuli, we employed a mouse model that selectively disrupts NMDA
      receptor function via NMDA receptor subunit NR1 (Grin1) knockout specifically in
      Cre-expressing CRF neurons. These animals (Cre+/(fGrin1+)) were compared with
      littermates lacking Cre expression (Cre-/(fGrin1+)). Following cue discrimination
      fear conditioning, male Cre+/(fGrin1+) mice showed increased fear expression to
      the tone paired with a foot shock (CS+) while still discriminating the CS+ from a
      tone never paired with a foot shock (CS-). In contrast to males, female mice
      learned and discriminated fear cues equivalently across the genotypes. Similarly,
      no genotype differences in sociability or social novelty were observed in female
      mice, but Cre+/(fGrin1+) males displayed greater naive sociability and preference
      for social novelty than Cre-/(fGrin1+) littermates. Furthermore, the level of
      social withdrawal exhibited by male Cre+/(fGrin1+) mice susceptible to social
      defeat stress relative to same genotype controls was significantly more
      pronounced than that displayed by susceptible Cre-/(fGrin1+) mice compared to
      control Cre-/(fGrin1+) mice. Together, these results demonstrate increased fear,
      social, and stress responsiveness specifically in male Cre+/(fGrin1+) mice. Our
      findings indicate that NMDA-mediated glutamatergic regulation of CRF neurons is
      important for appropriately regulating fear and social responses, likely
      functioning to promote survival under aversive circumstances. 

PMID- 25938742
TI  - Light-Activated Proteolysis for the Spatiotemporal Control of Proteins.
AB  - The regulation of proteolysis is an efficient way to control protein function in
      cells. Here, we present a general strategy enabling to increase the
      spatiotemporal resolution of conditional proteolysis by using light activation as
      trigger. Our approach relies on the auxin-inducible degradation system obtained
      by transposing components of the plant auxin-dependent degradation pathway in
      mammalian cells. We developed a photoactivatable auxin that acts as a
      photoactivatable inducer of degradation. Upon local and short light illumination,
      auxin is released in cells and triggers the degradation of a protein of interest
      with spatiotemporal control. 

PMID- 25938743
TI  - Pregnancy outcomes following exposure to efavirenz-based antiretroviral therapy
      in the Republic of Congo.
AB  - WHO recently recommended efavirenz (EFV) use for HIV infection through pregnancy,
      breastfeeding and childbearing age. However the use of EFV during pregnancy
      remains of concern and not all national guidelines reflect WHO advice. Few data
      are available concerning pregnancy outcomes. The objective of our study was to
      evaluate pregnancy outcomes in a cohort of women who conceived on EFV. A
      retrospective, multicenter cohort study was conducted in Pointe Noire, Republic
      of Congo (September 2005- June 2012). The following adverse pregnancy outcomes
      were considered: births defects, low birth weight, premature delivery, stillbirth
      and abortion, stratified by antiretroviral exposure at the time of conception.
      During the study period, 188 women conceived on antiretrovirals: 35 (18.6%) on
      EFV-based regimens and 153 (81.4%) on nevirapine-based regimens. Adverse
      pregnancy outcomes were observed in 17/35 (48.6%, 95% CI 33.0-64.4%) women in the
      EFV group and in 43/153 (28.1%, 95% CI 21.6-35.7%) in the non-EFV group
      (p=0.019). No birth defect was observed in either group. An increased incidence
      of adverse pregnancy outcomes was observed in the EFV group. As WHO is promoting
      a widespread use of EFV also for women in childbearing age, our study emphasizes
      the importance of launching large prospective cohort studies investigating
      pregnancy outcomes in exposed women. 

PMID- 25938744
TI  - Long-term changes in bone mineral density after switching to a protease inhibitor
      monotherapy in HIV-infected subject.
AB  - Although some clinical trials have studied the impact of treatments on bone
      mineral density (BMD), scarce data are available about the impact of protease
      inhibitor (PI) monotherapies on BMD. The aim of this study was to evaluate
      changes in BMD in patients after one, two, or three years of a PI monotherapy.
      This study included 46 HIV-infected patients who switched from a conventional
      triple antiretroviral strategy to a monotherapy with lopinavir/ritonavir (LPV/r)
      or darunavir/ritonavir (DRV/r) for one (one-year group, n=16), two (two-year
      group, n=20), and three (three-year group, n=10) years. BMD was assessed by dual
      energy X-ray absorptiometry (DXA). The median percentage of change in total femur
      BMD was 0.20% after one, 0.79% after two, and -0.31% after three years. The
      change in lumbar spine was -0.08%, -0.14%, and 0.50% % after the same years. No
      significant differences were found when patients were classified regarding the
      type of PI and whether or not had previously received PI or tenofovir. However,
      patients who interrupted tenofovir or those who started with DRV/r had a higher
      BMD increment. Patients who had taken non-nucleoside reverse transcriptase
      inhibitors previously decreased BMD when started PIs. Monotherapy treatment with
      ritonavir-boosted protease inhibitors (both LPV/r and DRV/r) during one, two, or
      three years leads to the stabilization of BMD in HIV-infected patients with long
      term virological suppression. Larger studies are necessary to compare the effect
      of starting or withdrawing PIs on BMD. 

PMID- 25938745
TI  - IL28B polymorphisms of both recipient and donor cooperate to influence IFN
      treatment response in HCV recurrence after liver transplantation, but IL28B SNPs
      of the recipient play a major role in IFN-induced blocking of HCV replication.
AB  - Single nucleotide polymorphisms (SNPs) of the IL28B locus are associated with a
      positive response to pegylated interferon-alpha and ribavirin (pegIFN-alpha/RBV)
      treatment of HCV-infected patients. This study evaluated the association between
      SNPs rs12980275, rs12979860 and rs8099917 and treatment outcome of HCV recurrent
      infection in HCV-positive patients who underwent liver transplant. We aimed to
      assess to what extent recipient and/or graft donor IL28B polymorphisms contribute
      to HCV clearance after transplantation influencing the response to the antiviral
      treatment. We found that the allele frequencies in donors were in agreement with
      the pattern expected in the European population. The frequency of favourable
      genotypes was significantly lower in recipients than in donors, reasonably
      because the recipients represented a group of patients affected by chronic
      Hepatitis C. Our study demonstrated that the positive outcome of the pegIFN
      alpha/RBV treatment of HCV recurrence is associated with the co-presence of
      favourable genotypes of both donors and recipients. However, IL28B SNPs of the
      recipient seem to play a major role in this clinical setting. In particular,
      homozygosis of rs12979860 favourable genotype in recipients was associated with
      sustained virological response independently from the donor's genotype. Thus,
      identification of these SNPs may be useful to predict the response to IFN-based
      therapy of HCV recurrent infection in liver-transplanted patients. 

PMID- 25938746
TI  - High-throughput genotyping of high-risk Human Papillomavirus by MALDI-TOF Mass
      Spectrometry-based method.
AB  - A high-throughput matrix-assisted laser desorption ionisation-time of flight
      (MALDI-TOF) mass spectrometry (MS)-based method was here developed to genotype 16
      high-risk human papillomavirus (HPV) types in cervical cytology specimens. This
      method was compared to a commercial kit, the Inno-LiPA HPV genotyping assay,
      which detects a broad spectrum of HPV types. HPV DNA was assessed by the two
      methods in a total of 325 cervical cytology specimens collected in PreservCyt(r)
      solution. The overall agreement was almost perfect (Cohen's k=0.86) in term of
      positive and negative cases. Indeed, HPV types 16, 35, 56 and 66 showed the
      highest agreement values (>0.80). The highest agreement values (K >0.80) were
      found for all 16 HPV types in single infections, but only for HPV 16, 35, 45 and
      56 in multiple infections. In conclusion, the high-throughput MS-based method
      developed here is well-suited for broad spectrum HPV genotyping in large-scale
      epidemiological studies. 

PMID- 25938747
TI  - Molecular characterisation of noroviruses detected in mussels (Mytilus
      galloprovincialis) from harvesting areas in Slovenia.
AB  - Noroviruses are a leading cause of viral gastroenteritis in humans and are
      responsible for many outbreaks worldwide. Mussels are one of the most important
      foodstuffs connected with norovirus outbreaks, also resulting in multinational
      dimensions. Two hundred and thirty-eight (238) samples of mussels (Mytilus
      galloprovincialis) were collected in periods between the years 2006-2008 and 2010
      2012 to study the prevalence of noroviruses (NoVs) from harvesting areas along
      the Adriatic coast of Slovenia. Between 2006 and 2008, 9.1% to 24.6% of mussel
      samples tested by specific GI and/or GII real-time RT-PCR methods were found to
      be positive for NoVs while between 2010 and 2012 the percentage of NoV positive
      samples varied from 12.5% to 22.2%. At the nucleotide level within the RdRp gene
      fragment the genetic diversity of NoVs detected in mussels ranged between 78.8
      81.0% nucleotide identity among GII strains (92.1-99.6% within the GII.P4
      genotype), 100% nucleotide identity among GI and 58.4-60.2% among GI and GII
      strains. Nine of the NoV strains detected from mussels were genotyped as GII.4,
      while two samples were within GI.P2 and one was a positive sample within genotype
      GII.P21. This study confirmed that mussels are a potential source of the NoV
      infection. The detected NoVs share the same topology on the phylogenetic tree
      within the NoV strains detected in water samples and human patients, not only
      from Slovenia but also from many different countries worldwide. We can assume
      that mussels in harvesting areas are not only contaminated from the surrounding
      area but also by contaminated water and sewage from large transport ships, which
      are regularly present in the area. 

PMID- 25938748
TI  - Characterization of Staphylococcus aureus small colony variant strains isolated
      from Italian patients attending a regional cystic fibrosis care centre.
AB  - Small colony variant (SCV) Staphylococcus aureus are a subpopulation of
      auxotroph, slow-growing strains causing persisting and relapsing infections in
      cystic fibrosis (CF) patients. Twenty-eight SCV and 29 normal S. aureus strains
      were isolated from 42 out of 222 Italian CF patients. The isolates were
      characterized for: susceptibility to antibiotics, methicillin-resistance (MR),
      Panton Valentine leukocidin, auxotrophy, hypermutability and biofilm formation.
      Clonal identity of SCV and normal strains was determined by pulsed-field gel
      electrophoresis. We found that 27 out of 28 SCVs were thymidine-dependent.
      Furthermore, in contrast to normal phenotype, SCVs were characterized by
      antibiotic resistance. We also found that 39.3% SCV vs 20.7% normal strains were
      strong mutators. Moreover, SCVs showed a higher capability to form biofilm
      compared to normal strains (100% vs 59%). Importantly, we found evidence of
      clonal spread of SCV strain among CF patients. Using molecular typing, we found
      that five patients shared the same type A and five out of seven MR-SCV belonged
      to the same clone (Clone C). The particular virulence and spreading ability of MR
      SCV observed highlights the importance of accurate identification and
      susceptibility testing of these strains. It is important to adopt the optimal
      approach to treat patients and to prevent cross-infection in CF centres. 

PMID- 25938749
TI  - Direct identification of microorganisms from positive blood cultures using the
      lysis-filtration technique and matrix assisted laser desorption ionization time
      of-flight mass spectrometry (MALDI-TOF MS): a multicentre study.
AB  - Microbial identification from blood cultures is essential to institute optimal
      antibiotic therapy and improve survival possibilities. Matrix-assisted laser
      desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been
      successfully applied to identify bacteria and yeasts from positive blood cultures
      broths. The aim of this multicentre study was to evaluate the reliability of the
      lysis-filtration technique associated with MALDI-TOF MS to directly identify
      microorganisms from 765 positive blood cultures collected in six Italian
      hospitals. Overall, 675/765 (78.1%) blood isolates were correctly identified at
      the species level, with significant differences between Gram-negative and Gram
      positive bacteria (92.6%, and 69.8%, respectively). Some difficulties arise in
      identifying Streptococcus pneumoniae, Staphylococcus aureus, yeasts and
      anaerobes. The lysis-filtration protocol is a suitable procedure in terms of
      performance in identifying microorganisms, but it is quite expensive and
      technically time-consuming since the time of filtration is not regular for all
      the samples. The application of the MALDI-TOF MS technique to the direct
      microbial identification from positive blood cultures is a very promising
      approach, even if more experience must be gained to minimize errors and costs. 

PMID- 25938750
TI  - Development of a real-time PCR assay for the rapid detection of Acinetobacter
      baumannii from whole blood samples.
AB  - Acinetobacter baumannii is a multidrug-resistant pathogen associated with severe
      infections in hospitalized patients, including pneumonia, urinary and bloodstream
      infections. Rapid detection of A. baumannii infection is crucial for timely
      treatment of septicemic patients. The aim of the present study was to develop a
      specific marker for a quantitative polymerase chain reaction (PCR) assay for the
      detection of A. baumannii. The target gene chosen is the biofilm-associated
      protein (bap) gene, encoding a cell surface protein involved in biofilm
      formation. The assay is specific for A. baumannii, allowing its discrimination
      from different species of Acinetobacter and other clinically relevant bacterial
      pathogens. The assay is able to detect one genomic copy of A. baumannii,
      corresponding to 4 fg of purified DNA, and 20 colony-forming units/ml using DNA
      extracted from spiked whole blood samples. 

PMID- 25938751
TI  - Nutritionally Variant Streptococci Interfere with Streptococcus mutans Adhesion
      Properties and Biofilm Formation.
AB  - The bacterial species Streptococcus mutans is known as the main cause of dental
      caries in humans. Therefore, much effort has focused on preventing oral
      colonization by this strain or clearing it from oral tissues. The oral cavity is
      colonized by several bacterial species that constitute the commensal oral flora,
      but none of these is able to interfere with the cariogenic properties of S.
      mutans. This paper describes the interfering ability of some nutritionally
      variant streptococcal strains (NVS) with S. mutans adhesion to glass surfaces and
      also to hydroxylapatite. In mixed cultures, NVS induce a complete inhibition of
      S. mutans microcolony formation on cover glass slides. NVS can also block the
      adherence of radiolabeled S. mutans to hydroxylapatite in the presence of both
      saliva and sucrose. The analysis of the action mechanism of NVS demonstrated that
      NVS are more hydrophobic than S. mutans and adhere tightly to hard surfaces. In
      addition, a cell-free culture filtrate of NVS was also able to interfere with S.
      mutans adhesion to hydroxylapatite. Since NVS are known to secrete some important
      bacteriolytic enzymes, we conclude that NVS can be a natural antagonist to the
      cariogenic properties of S. mutans. 

PMID- 25938752
TI  - Enzymatic assay to test diamines produced by vaginal bacteria.
AB  - An enzymatic assay was developed to determine the concentration of diamines (DA)
      in clinical samples of vaginal fluids. Putrescine and cadaverine are DA produced
      by anaerobic bacteria and are typically present in the vaginal fluids of women
      with an abnormal microbiota, as occurs in bacterial vaginosis. The vaginal DA
      (VADA) assay is based on the enzyme diamine oxidase which reacts with putrescine
      and cadaverine to produce H2O2 in a quantitative manner. H2O2 concentration is
      measured spectrophotometrically by a chromogenic reaction catalyzed by
      horseradish peroxidase. The VADA assay proved to be capable of detecting DA
      concentrations as low as 4 mM and showed a dose-response relationship which was
      linear over DA concentrations ranging from 4 to 256 mM. Using clinical samples it
      was possible to show that the VADA assay can be performed on human vaginal swabs
      and that the mean DA concentration is significantly higher in samples positive
      for microbial pathogens. 

PMID- 25938753
TI  - Identification of plasmid OXA and other beta-lactamase genes among carbapenem
      resistant isolates of Pseudomonas aeruginosa from the Clinical University
      Hospital in northeastern Poland.
AB  - The aim of the study was to evaluate the prevalence of OXA and other beta
      lactamase genes, antibiotic susceptibility, and the genetic relatedness among
      clinical isolates of P. aeruginosa resistant to carbapenems. The presence of bla-
      OXA genes was demonstrated in 48% of isolates belonging to four PFGE profiles.
      Most of them contained the blaOXA-2 gene (88.3%). Other blaOXA genes (Ps1310 with
      blaOXA-30 and Ps1309 with blaOXA-10) were found in only two isolates. The tested
      isolates also contained other beta-lactamase genes such as blaVIM-2, blaVIM-4,
      blaSHV-5, and blaTEM-1. All isolates were susceptible only to colistin (100%). 

PMID- 25938754
TI  - Comparison of two methods for the detection of verotoxin producing E.coli in
      human faecal samples during an outbreak of HUS in Apulia, Southern Italy.
AB  - This study evaluated the diagnostic performances of an ELISA method and a
      molecular method for the detection of verotoxin in faecal samples during an
      outbreak of haemolytic-uraemic syndrome (HUS) occurring in Apulia, Southern
      Italy. Two of the 16 faecal samples were positive for verotoxin when analysed by
      ELISA and resulted PCR positive for stx1, stx2, eaeA and serogroup O26. The other
      14 faecal samples resulted negative with both tests. The detection of verotoxin
      in faecal samples by ELISA is a simple, sensitive, specific and rapid method (2
      hours) of considerable utility for routine clinical testing laboratories without
      access to more specialized diagnostic procedures. 

PMID- 25938755
TI  - Clonality and Antimicrobial Susceptibility of Burkholderia cepacia complex
      Isolates Collected from Cystic Fibrosis Patients during 1998-2013 in Bern,
      Switzerland.
AB  - For the first time, we analyzed the clonality and susceptibility of Burkholderia
      cepacia complex isolates (n=55) collected during 1998-2013 from 44 Swiss cystic
      fibrosis (CF)-patients. B. cenocepacia (n=28) and B. multivorans (n=14) were
      mainly of sequence type (ST) 833 and ST874, respectively; B. contaminans isolates
      were of ST102. Overall, the following MIC50/90s (mg/l) were obtained:
      piperacillin/tazobactam (<= 4/>= 128), ticarcillin/clavulanate (>= 256/>=256),
      ceftazidime (2/>= 32), aztreonam (16/>= 32), meropenem (2/8), tobramycin (8/>=
      16), minocycline (<= 1/16), levofloxacin (<= 0.5/>= 16), and
      trimethoprim/sulfamethoxazole (<= 0.5/4). This is the first survey providing
      information on the clonality of Bcc detected in Switzerland. Species
      identification and antimicrobial susceptibility tests should always be routinely
      performed to adapt more targeted therapies.

PMID- 25938756
TI  - Durable viral suppression in an HIV-infected patient in the absence of
      antiretroviral therapy.
AB  - We describe the case of a young woman with an acute HIV infection characterized
      at onset by neurological features. The patient spontaneously controlled her HIV
      infection and recovered in a short period of time. The patient's clinical and
      virological history showed a peculiar evolution of HIV infection, with an MDR HIV
      1 in CSF and a wild HIV strain in PBMCs. The patient's PBMC showed a rapid shift
      from a wild type to an MDR strain in few days. 

PMID- 25938757
TI  - A novel mutation leading to a premature stop codon in inlA of Listeria
      monocytogenes isolated from neonatal listeriosis.
AB  - The study objective was to investigate whether the strain of L. monocytogenes
      serotype 1/2c isolated from neonatal listeriosis carries a premature stop codon
      (PMSC) mutation in the inlA gene. The strain was characterized by serotyping,
      macrorestriction analysis after digestion with the restriction enzyme AscI, and
      sequencing of the inlA gene. The tested strain of serotype 1/2c and pulsotype 1
      possesses a new type of point mutation leading to a PMSC in the inlA gene and
      production of truncated internalin A. The case of early onset form of neonatal
      listeriosis caused by serotype 1/2c with a PMSC mutation in the inlA gene
      confirmed the transplacental transmission potential of this strain. 

PMID- 25938758
TI  - Distribution characteristics of phosphorus in the sediments and overlying water
      of Poyang lake.
AB  - Phosphorus (P) is a key indicator of the aquatic organism growth and
      eutrophication in lakes. The distribution and speciation of P and its release
      characteristics from sediments were investigated by analyzing sediment and water
      samples collected during high flow and low flow periods. Results showed that the
      average concentrations (ranges) of total phosphorus (TP) in the surface and deep
      water were 0.06 mg L(-1) (0.03-0.13 mg L(-1)) and 0.15 mg L(-1) (0.06-0.33 mg L(
      1)), respectively, while the average concentration (range) of TP in sediments was
      709.17 mg kg(-1) (544.76-932.11 mg kg(-1)). The concentrations of TP and
      different forms of P varied spatially in the surface sediments, displaying a
      decreasing trend from south to north. P also varied topographically from
      estuarine areas to lake areas. The vertical distribution of TP and different
      forms of P were observed to decrease as depth increased. The P concentrations
      during the low flow period were higher than those during the high flow period.
      Inorganic phosphorus (IP) was the dominant form of P, accounting for 61%-82% of
      TP. The concentration of bioavailable phosphorus in sediments was relatively
      large, indicating a high risk of release to overlying water. The simulation
      experiment of P release from sediments showed that the release was relatively
      fast in the first 0-5 min and then decreased to a plateau after 1 hr.
      Approximately 84-89% of the maximum amount of P was released during the first
      hour.

PMID- 25938759
TI  - Pioneer accountable care organizations: traversing rough country.

PMID- 25938760
TI  - A Fault Diagnosis Methodology for Gear Pump Based on EEMD and Bayesian Network.
AB  - This paper proposes a fault diagnosis methodology for a gear pump based on the
      ensemble empirical mode decomposition (EEMD) method and the Bayesian network.
      Essentially, the presented scheme is a multi-source information fusion based
      methodology. Compared with the conventional fault diagnosis with only EEMD, the
      proposed method is able to take advantage of all useful information besides
      sensor signals. The presented diagnostic Bayesian network consists of a fault
      layer, a fault feature layer and a multi-source information layer. Vibration
      signals from sensor measurement are decomposed by the EEMD method and the energy
      of intrinsic mode functions (IMFs) are calculated as fault features. These
      features are added into the fault feature layer in the Bayesian network. The
      other sources of useful information are added to the information layer. The
      generalized three-layer Bayesian network can be developed by fully incorporating
      faults and fault symptoms as well as other useful information such as naked eye
      inspection and maintenance records. Therefore, diagnostic accuracy and capacity
      can be improved. The proposed methodology is applied to the fault diagnosis of a
      gear pump and the structure and parameters of the Bayesian network is
      established. Compared with artificial neural network and support vector machine
      classification algorithms, the proposed model has the best diagnostic performance
      when sensor data is used only. A case study has demonstrated that some
      information from human observation or system repair records is very helpful to
      the fault diagnosis. It is effective and efficient in diagnosing faults based on
      uncertain, incomplete information. 

PMID- 25938761
TI  - Recognition of Linear B-Cell Epitope of Betanodavirus Coat Protein by RG-M18
      Neutralizing mAB Inhibits Giant Grouper Nervous Necrosis Virus (GGNNV) Infection.
AB  - Betanodavirus is a causative agent of viral nervous necrosis syndrome in many
      important aquaculture marine fish larvae, resulting in high global mortality. The
      coat protein of Betanodavirus is the sole structural protein, and it can assemble
      the virion particle by itself. In this study, we used a high-titer neutralizing
      mAB, RG-M18, to identify the linear B-cell epitope on the viral coat protein. By
      mapping a series of recombinant proteins generated using the E. coli PET
      expression system, we demonstrated that the linear epitope recognized by RG-M18
      is located at the C-terminus of the coat protein, between amino acid residues 195
      and 338. To define the minimal epitope region, a set of overlapping peptides were
      synthesized and evaluated for RG-M18 binding. Such analysis identified the
      195VNVSVLCR202 motif as the minimal epitope. Comparative analysis of Alanine
      scanning mutagenesis with dot-blotting and ELISA revealed that Valine197,
      Valine199, and Cysteine201 are critical for antibody binding. Substitution of
      Leucine200 in the RGNNV, BFNNV, and TPNNV genotypes with Methionine200 (thereby
      simulating the SJNNV genotype) did not affect binding affinity, implying that RG
      M18 can recognize all genotypes of Betanodaviruses. In competition experiments,
      synthetic multiple antigen peptides of this epitope dramatically suppressed giant
      grouper nervous necrosis virus (GGNNV) propagation in grouper brain cells. The
      data provide new insights into the protective mechanism of this neutralizing mAB,
      with broader implications for Betanodavirus vaccinology and antiviral peptide
      drug development. 

PMID- 25938762
TI  - A Dengue Virus Type 4 Model of Disseminated Lethal Infection in AG129 Mice.
AB  - Dengue is a mosquito-borne disease of global public health significance that is
      caused by four serologically and genetically related viruses (DENV-1 to DENV-4).
      Most human DENV infections are asymptomatic, but clinical cases can range in
      severity from a relatively mild self-limiting illness to a severe life
      threatening disease. Infection with one serotype of DENV results in life-long
      homotypic immunity but only short term heterotypic protection. There are no
      licensed vaccines or antivirals for dengue due in part to difficulty in
      developing small animal models that mimic the systemic disease seen in humans.
      Consequently, an important advance was the description of models of DENV-2
      infection in AG129 mice (deficient in interferon alpha/beta and gamma receptor
      signaling) that resemble human disease. However, the need for well characterized
      models of disease due to DENV-1, -3, and -4 still remains. Here we describe a new
      AG129 mouse model utilizing a non-mouse-adapted Thai human DENV-4 strain 703-4.
      Following intraperitoneal challenge, animals experience a rapidly progressive
      lethal infection without developing neurologic clinical signs of disease. High
      virus titers are seen in multiple visceral tissues including the liver, spleen
      and large intestine, and the infected animals develop vascular leakage and
      thrombocytopenia, hallmarks of human dengue. Taken together, our studies
      demonstrate that this model is an important addition to the field of dengue
      research particularly in understanding similarities and differences in the
      pathologic basis of the disease caused by different DENV serotypes and in
      determining comparative efficacy of putative vaccines and antivirals. 

PMID- 25938763
TI  - Bimetallic nanoparticles for arsenic detection.
AB  - Effective and sensitive monitoring of heavy metal ions, particularly arsenic, in
      drinking water is very important to risk management of public health. Arsenic is
      one of the most serious natural pollutants in soil and water in more than 70
      countries in the world. The need for very sensitive sensors to detect ultralow
      amounts of arsenic has attracted great research interest. Here, bimetallic FePt,
      FeAu, FePd, and AuPt nanoparticles (NPs) are electrochemically deposited on the
      Si(100) substrate, and their electrochemical properties are studied for As(III)
      detection. We show that trace amounts of As(III) in neutral pH could be
      determined by using anodic stripping voltammetry. The synergistic effect of
      alloying with Fe leads to better performance for Fe-noble metal NPs (Au, Pt, and
      Pd) than pristine noble metal NPs (without Fe alloying). Limit of detection and
      linear range are obtained for FePt, FeAu, and FePd NPs. The best performance is
      found for FePt NPs with a limit of detection of 0.8 ppb and a sensitivity of 0.42
      MUA ppb(-1). The selectivity of the sensor has also been tested in the presence
      of a large amount of Cu(II), as the most detrimental interferer ion for As
      detection. The bimetallic NPs therefore promise to be an effective, high
      performance electrochemical sensor for the detection of ultratrace quantities of
      arsenic. 

PMID- 25938765
TI  - Morphologic and Aerodynamic Considerations Regarding the Plumed Seeds of
      Tragopogon pratensis and Their Implications for Seed Dispersal.
AB  - Tragopogon pratensis is a small herbaceous plant that uses wind as the dispersal
      vector for its seeds. The seeds are attached to parachutes that increase the
      aerodynamic drag force and increase the total distance travelled. Our hypothesis
      is that evolution has carefully tuned the air permeability of the seeds to
      operate in the most convenient fluid dynamic regime. To achieve final
      permeability, the primary and secondary fibres of the pappus have evolved with
      complex weaving; this maximises the drag force (i.e., the drag coefficient), and
      the pappus operates in an "optimal" state. We used computational fluid dynamics
      (CFD) simulations to compute the seed drag coefficient and compare it with data
      obtained from drop experiments. The permeability of the parachute was estimated
      from microscope images. Our simulations reveal three flow regimes in which the
      parachute can operate according to its permeability. These flow regimes impact
      the stability of the parachute and its drag coefficient. From the permeability
      measurements and drop experiments, we show how the seeds operate very close to
      the optimal case. The porosity of the textile appears to be an appropriate
      solution to achieve a lightweight structure that allows a low terminal velocity,
      a stable flight and a very efficient parachute for the velocity at which it
      operates. 

PMID- 25938764
TI  - Life Course Trajectories of Labour Market Participation among Young Adults Who
      Experienced Severe Alcohol-Related Health Outcomes: A Retrospective Cohort Study.
AB  - BACKGROUND: Long-term employment trajectories of young problem drinkers are
      poorly understood. METHODS: We constructed retrospective labour market
      participation histories at ages 18-34 of 64 342 persons born in 1969-1982.
      Beginning from the year of each subject's 18th birthday, we extracted information
      from the records of Statistics Finland on educational attainment, main type of
      economic activity, months in employment, and months in unemployment for a minimum
      of seven years (range 7-16 years). We used information on the timing of alcohol
      related hospitalizations and deaths in the same period to define problem drinkers
      with early onset limited course, early onset persistent course, and late onset
      problem drinking. RESULTS: Early onset limited course problem drinkers improved
      their employment considerably by age, whereas early onset persistent problem
      drinkers experienced a constant decline in their employment by age. From the age
      of 18 to 34, early onset persistent problem drinkers were in employment merely
      12% of the time, in comparison with 39% among the early onset limited course
      problem drinkers, and 58% among the general population. CONCLUSIONS: These
      results indicate that young adults who were retrospectively defined as having
      early onset persistent course problem drinking were extensively marginalized from
      the labour market early on during their life course, and that their employment
      trajectory was significantly worse compared to other problem drinkers.

PMID- 25938766
TI  - A metabolomic study of rats with doxorubicin-induced cardiomyopathy and Shengmai
      injection treatment.
AB  - Doxorubicin-induced cardiomyopathy (DOX-CM) is a severe complication of
      doxorubicin (DOX) chemotherapy. Characterized by cumulative and irreversible
      myocardial damage, its pathogenesis has not been fully elucidated. Shengmai
      Injection (SMI), a Traditional Chinese Medicine, may alleviate myocardial injury
      and improve heart function in the setting of DOX-CM. As a result of its multi
      component and multi-target nature and comprehensive regulation, the
      pharmacological mechanisms underlying SMI's effects remain obscure. The emerging
      field of metabolomics provides a potential approach with which to explore the
      pathogenesis of DOX-CM and the benefits of SMI treatment. DOX-CM was induced in
      rats via intraperitoneal injections of DOX. Cardiac metabolic profiling was
      performed via gas chromatography/mass spectrometry and ultra-performance liquid
      chromatography/tandem mass spectrometry. A bioinformatics analysis was conducted
      via Ingenuity Pathway Analysis (IPA). Eight weeks following DOX treatment,
      significant cardiac remodeling, dysfunction and metabolic perturbations were
      observed in the rats with DOX-CM. The metabolic disturbances primarily involved
      lipids, amino acids, vitamins and energy metabolism, and may have been indicative
      of both an energy metabolism disorder and oxidative stress secondary to DOX
      chemotherapy. However, SMI improved cardiac structure and function, as well as
      the metabolism of the rats with DOX-CM. The metabolic alterations induced via
      SMI, including the promotion of glycogenolysis, glycolysis, amino acid
      utilization and antioxidation, suggested that SMI exerts cardioprotective effects
      by improving energy metabolism and attenuating oxidative stress. Moreover, the
      IPA revealed that important signaling molecules and enzymes interacted with the
      altered metabolites. These findings have provided us with new insights into the
      pathogenesis of DOX-CM and the effects of SMI, and suggest that the combination
      of metabolomic analysis and IPA may represent a promising tool with which to
      explore and better understand both heart disease and TCM therapy. 

PMID- 25938767
TI  - An enzymatic method to rescue mesenchymal stem cells from clotted bone marrow
      samples.
AB  - Mesenchymal stem cells (MSCs) - usually obtained from bone marrow - often require
      expansion culture. Our protocol uses clinical grade urokinase to degrade clots in
      the bone marrow and release MSCs for further use. This protocol provides a rapid
      and inexpensive alternative to bone marrow resampling. Bone marrow is a major
      source of MSCs, which are interesting for tissue engineering and autologous stem
      cell therapies. Upon withdrawal bone marrow may clot, as it comprises all of the
      hematopoietic system. The resulting clots contain also MSCs that are lost for
      expansion culture or direct stem cell therapy. We experienced that 74% of canine
      bone marrow samples contained clots and yielded less than half of the stem cell
      number expected from unclotted samples. Thus, we developed a protocol for
      enzymatic digestion of those clots to avoid labor-intense and costly bone marrow
      resampling. Urokinase - a clinically approved and readily available thrombolytic
      drug - clears away the bone marrow clots almost completely. As a consequence,
      treated bone marrow aspirates yield similar numbers of MSCs as unclotted samples.
      Also, after urokinase treatment the cells kept their metabolic activity and the
      ability to differentiate into chondrogenic, osteogenic and adipogenic lineages.
      Our protocol salvages clotted blood and bone marrow samples without affecting the
      quality of the cells. This obsoletes resampling, considerably reduces sampling
      costs and enables the use of clotted samples for research or therapy. 

PMID- 25938768
TI  - Vitamin D intake, month the mammogram was taken and mammographic density in
      Norwegian women aged 50-69.
AB  - BACKGROUND: The role of vitamin D in breast cancer etiology is unclear. There is
      some, but inconsistent, evidence that vitamin D is associated with both breast
      cancer risk and mammographic density (MD). We evaluated the associations of MD
      with month the mammogram was taken, and with vitamin D intake, in a population of
      women from Norway--a country with limited sunlight exposure for a large part of
      the year. METHODS: 3114 women aged 50-69, who participated in the Norwegian
      Breast Cancer Screening Program (NBCSP) in 2004 or 2006/07, completed risk factor
      and food frequency (FFQ) questionnaires. Dietary and total (dietary plus
      supplements) vitamin D, calcium and energy intakes were estimated by the FFQ.
      Month when the mammogram was taken was recorded on the mammogram. Percent MD was
      assessed using a computer assisted method (Madena, University of Southern
      California) after digitization of the films. Linear regression models were used
      to investigate percent MD associations with month the mammogram was taken, and
      vitamin D and calcium intakes, adjusting for age, body mass index (BMI), study
      year, estrogen and progestin therapy (EPT), education, parity, calcium intakes
      and energy intakes. RESULTS: There was no statistical significant association
      between the month the mammogram was taken and percent MD. Overall, there was no
      association between percent MD and quartiles of total or dietary vitamin D
      intakes, or of calcium intake. However, analysis restricted to women aged <55
      years revealed a suggestive inverse association between total vitamin D intake
      and percent MD (p for trend = 0.03). CONCLUSION: Overall, we found no strong
      evidence that month the mammogram was taken was associated with percent MD. We
      found no inverse association between vitamin D intake and percent MD overall, but
      observed a suggestive inverse association between dietary vitamin D and MD for
      women less than 55 years old.

PMID- 25938769
TI  - Treatment age, dose and sex determine neuroanatomical outcome in irradiated
      juvenile mice.
AB  - Pediatric cranial radiation therapy can induce long-term neurocognitive deficits,
      the risk and severity of these deficits are amplified in females and in those
      individuals exposed at a younger age and/or those irradiated at higher doses. To
      investigate the developmental consequences of these factors in greater detail,
      male and female C57Bl/6J mice between infancy and late childhood (16 and 36 days)
      were irradiated at a single time point with a whole-brain dose of 0, 3, 5 or 7
      Gy. In vivo and ex vivo magnetic resonance imaging (MRI) and deformation-based
      morphometry was used to identify radiation-induced volume differences. As
      expected, exposure to 7 Gy of radiation at 16 days of age induced widespread
      volume deficits that were largely mitigated by increasing treatment age or
      decreasing dose. Notable exceptions were regions in the olfactory bulbs and
      hippocampus that displayed both a detectable difference in volume and a loss in
      neurogenesis for most doses and ages. Furthermore, white matter regions located
      at the front of the brain remained sensitive to radiation at later treatment
      ages, compared to regions at the back. Differences due to sex were subtle, with
      increased radiosensitivity in females detectable only in the mammillary bodies
      and fornix. Our results reveal anatomical alterations in brain development
      consistent with expectations based on pediatric patient neurocognitive outcomes.
      This data demonstrates that neuroimaging of the mouse is an effective tool for
      investigating radiation-induced late effects. 

PMID- 25938771
TI  - Radiation-induced epigenetic bystander effects demonstrated in Arabidopsis
      thaliana.
AB  - Radiation-induced bystander effects (RIBE) in vivo in the higher plant
      Arabidopsis thaliana ( A. thaliana ) have been well demonstrated in terms of
      effects on development and genetics. However, there is not yet robust evidence
      regarding RIBE-mediated epigenetic changes in plants. To address this, in the
      current work the roots of A. thaliana seedlings were locally irradiated with 10
      Gy of alpha particles, after which DNA methylation in bystander aerial plants
      were detected using the methylation-sensitive amplification polymorphism (MSAP)
      and bisulfite sequencing PCR (BSP). Results showed that irradiation of the roots
      led to long-distance changes in DNA methylation patterns at some CCGG sites over
      the whole genome, specifically from hemi-methylation to non-methylation, and the
      methylation ratios, mainly at CG sites, strongly indicating the existence of RIBE
      mediated epigenetic changes in higher plants. Root irradiation also influenced
      expressions of DNA methylation-related MET1, DRM2 and SUVH4 genes and
      demethylation-related DML3 gene in bystander aerial plants, suggesting a
      modulation of RIBE to the methylation machinery in plants. In addition, the
      multicopy P35S:GUS in A. thaliana line L5-1, which is silenced epigenetically by
      DNA methylation and histone modification, was transcriptionally activated through
      the RIBE. The transcriptional activation could be significantly inhibited by the
      treatment with reactive oxygen species (ROS) scavenger dimethyl sulfoxide (DMSO),
      indicative of a pivotal role of ROS in RIBE-mediated epigenetic changes. Time
      course analyses showed that the bystander signaling molecule(s) for
      transcriptional activation of multicopy P35S:GUS, although of unknown chemical
      nature, were generated in the root cells within 24 h postirradiation. 

PMID- 25938770
TI  - Cellular and molecular mechanisms underlying oxygen-dependent radiosensitivity.
AB  - Molecular oxygen has long been recognized as a powerful radiosensitizer that
      enhances the cell-killing efficiency of ionizing radiation. Radiosensitization by
      oxygen occurs at very low concentrations with the half-maximum radiosensitization
      at approximately 3 mmHg. However, robust hypoxia-induced signal transduction can
      be induced at <15 mmHg and can elicit a wide range of cellular responses that
      will affect therapy response as well as malignant progression. Great strides have
      been made, especially since the 1990s, toward identification and characterization
      of the oxygen-regulated molecular pathways that affect tumor response to ionizing
      radiation. In this review, we will discuss the current advances in our
      understanding of oxygen-dependent molecular modification and cellular signal
      transduction and their impact on tumor response to therapy. We will specifically
      address mechanistic distinctions between radiobiological hypoxia (0-3 mmHg) and
      pathological hypoxia (3-15 mmHg). We also propose a paradigm that hypoxia
      increases radioresistance by maintaining the cancer stem cell phenotype. 

PMID- 25938772
TI  - Fibroblast-Derived Exosomes Contribute to Chemoresistance through Priming Cancer
      Stem Cells in Colorectal Cancer.
AB  - Chemotherapy resistance observed in patients with colorectal cancer (CRC) may be
      related to the presence of cancer stem cells (CSCs), but the underlying
      mechanism(s) remain unclear. Carcinoma-associated fibroblasts (CAFs) are
      intimately involved in tumor recurrence, and targeting them increases chemo
      sensitivity. We investigated whether fibroblasts might increase CSCs thus
      mediating chemotherapy resistance. CSCs were isolated from either patient-derived
      xenografts or CRC cell lines based on expression of CD133. First, CSCs were found
      to be inherently resistant to cell death induced by chemotherapy. In addition,
      fibroblast-derived conditioned medium (CM) promoted percentage, clonogenicity and
      tumor growth of CSCs (i.e., CD133+ and TOP-GFP+) upon treatment with 5
      fluorouracil (5-Fu) or oxaliplatin (OXA). Further investigations exhibited that
      exosomes, isolated from CM, similarly took the above effects. Inhibition of
      exosome secretion decreased the percentage, clonogenicity and tumor growth of
      CSCs. Altogether, our findings suggest that, besides targeting CSCs, new
      therapeutic strategies blocking CAFs secretion even before chemotherapy shall be
      developed to gain better clinical benefits in advanced CRCs. 

PMID- 25938773
TI  - Cold Responsive Gene Expression Profiling of Sugarcane and Saccharum spontaneum
      with Functional Analysis of a Cold Inducible Saccharum Homolog of NOD26-Like
      Intrinsic Protein to Salt and Water Stress.
AB  - Transcriptome analysis of sugarcane hybrid CP72-1210 (cold susceptible) and
      Saccharum spontaneum TUS05-05 (cold tolerant) using Sugarcane Assembled Sequences
      (SAS) from SUCEST-FUN Database showed that a total of 35,340 and 34,698 SAS
      genes, respectively, were expressed before and after chilling stress. The
      analysis revealed that more than 600 genes are differentially expressed in each
      genotype after chilling stress. Blast2Go annotation revealed that the major
      difference in gene expression profiles between CP72-1210 and TUS05-05 after
      chilling stress are present in the genes related to the transmembrane transporter
      activity. To further investigate the relevance of transmembrane transporter
      activity against abiotic stress tolerance, a S. spontaneum homolog of a NOD26
      like major intrinsic protein gene (SspNIP2) was selected for functional analysis,
      of which expression was induced after chilling stress in the cold tolerant TUS05
      05. Quantitative real-time PCR showed that SspNIP2 expression was increased ~2.5
      fold at 30 minutes after cold treatment and stayed induced throughout the 24
      hours of cold treatment. The amino acid sequence analysis of the cloned SspNIP2
      confirmed the presence of six transmembrane domains and two NPA (Asn-Pro-Ala)
      motifs, signature features of major intrinsic protein families. Amino acid
      analysis confirmed that four amino acids, comprising the ar/R (aromatic
      residue/arginine) region responsible for the substrate specificity among MIPs,
      are conserved among monocot silicon transporters and SspNIP2. Salinity stress
      test on SspNIP2 transgenic tobacco plants resulted in more vigorous transgenic
      lines than the non-transgenic tobacco plants, suggesting some degree of tolerance
      to salt stress conferred by SspNIP2. SspNIP2-transgenic plants, exposed to 2
      weeks of water stress without irrigation, developed various degrees of water
      stress symptom. The water stress test confirmed that the SspNIP2 transgenic lines
      had lower evapotranspiration rates than non-transgenic lines, suggesting that
      SspNIP2 transgenic lines showed a slight tolerance to the early water stress
      compared to wild type plants. 

PMID- 25938775
TI  - Correction: the human footprint in Mexico: physical geography and historical
      legacies.

PMID- 25938774
TI  - Antibiotic toxicity and absorption in zebrafish using liquid chromatography
      tandem mass spectrometry.
AB  - Evaluation of drug toxicity is necessary for drug safety, but in vivo drug
      absorption is varied; therefore, a rapid, sensitive and reliable method for
      measuring drugs is needed. Zebrafish are acceptable drug toxicity screening
      models; we used these animals with a liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) method in a multiple reaction monitoring mode to quantify
      drug uptake in zebrafish to better estimate drug toxicity. Analytes were
      recovered from zebrafish homogenate by collecting supernatant. Measurements were
      confirmed for drugs in the range of 10-1,000 ng/mL. Four antibiotics with
      different polarities were tested to explore any correlation of drug polarity,
      absorption, and toxicity. Zebrafish at 3 days post-fertilization (dpf) absorbed
      more drug than those at 6 h post-fertilization (hpf), and different developmental
      periods appeared to be differentially sensitive to the same compound. By
      observing abnormal embryos and LD50 values, zebrafish embryos at 6 hpf were
      considered to be suitable for evaluating embryotoxicity. Also, larvae at 3 dpf
      were adapted to measure acute drug toxicity in adult mammals. Thus, we can
      exploit zebrafish to study drug toxicity and can reliably quantify drug uptake
      with LC-MS/MS. This approach will be helpful for future studies of toxicology in
      zebrafish. 

PMID- 25938776
TI  - Identification of Plasmodium falciparum DNA Repair Protein Mre11 with an
      Evolutionarily Conserved Nuclease Function.
AB  - The eukaryotic Meiotic Recombination protein 11 (Mre11) plays pivotal roles in
      the DNA damage response (DDR). Specifically, Mre11 senses and signals DNA double
      strand breaks (DSB) and facilitates their repair through effector proteins
      belonging to either homologous recombination (HR) or non-homologous end joining
      (NHEJ) repair mechanisms. In the human malaria parasite Plasmodium falciparum, HR
      and alternative-NHEJ have been identified; however, little is known about the
      upstream factors involved in the DDR of this organism. In this report, we
      identify a putative ortholog of Mre11 in P. falciparum (PfalMre11) that shares
      22% sequence similarity to human Mre11. Homology modeling reveals striking
      structural resemblance of the predicted PfalMre11 nuclease domain to the nuclease
      domain of Saccharomyces cerevisiae Mre11 (ScMre11). Complementation analyses
      reveal functional conservation of PfalMre11 nuclease activity as demonstrated by
      the ability of the PfalMre11 nuclease domain, in conjunction with the C-terminal
      domain of ScMre11, to functionally complement an mre11 deficient yeast strain.
      Functional complementation was virtually abrogated by an amino acid substitution
      in the PfalMre11 nuclease domain (D398N). PfalMre11 is abundant in the
      mitotically active trophozoite and schizont stages of P. falciparum and is up
      regulated in response to DNA damage, suggesting a role in the DDR. PfalMre11
      exhibits physical interaction with PfalRad50. In addition, yeast 2-hybrid studies
      show that PfalMre11 interacts with ScRad50 and ScXrs2, two important components
      of the well characterized Mre11-Rad50-Xrs2 complex which is involved in DDR
      signaling and repair in S. cerevisiae, further supporting a role for PfalMre11 in
      the DDR. Taken together, these findings provide evidence that PfalMre11 is an
      evolutionarily conserved component of the DDR in Plasmodium. 

PMID- 25938777
TI  - Analysis of polynuclear aromatic hydrocarbons in olive oil after solid-phase
      extraction using a dual-layer sorbent cartridge followed by high-performance
      liquid chromatography with fluorescence detection.
AB  - A simple and easy direct solid-phase extraction (SPE) method was developed for
      the analysis of polynuclear aromatic hydrocarbons (PAHs) in olive oil using a
      dual-layer cartridge containing activated Florisil and a mixture of octadecyl
      (C18)-bonded and zirconia-coated silicas. Undiluted olive oil was applied
      directly to the SPE cartridge, and the sample was eluted with acetonitrile
      solvent. Background in the extract was found to be low enough for either gas
      chromatography-mass spectrometry (GC-MS) or high-performance liquid
      chromatography with fluorescence detection (HPLC-FLD) analysis. Average
      recoveries for 16 different PAHs from spiked olive oil replicates were >75%, with
      intraday precisions of <20% relative standard deviation (% RSD). Detection limits
      ranged from 0.2 to 1.0 MUg/kg and, specifically for the PAHs listed in EC
      Regulation 835/2011, benzo(a)anthracene, chrysene, benzo(b)fluoranthene, and
      benzo(a)pyrene, were from 0.3 to 0.7 MUg/kg. The method was then applied to
      determine the PAH content present in commercial samples of refined versus extra
      virgin olive oils. 

PMID- 25938778
TI  - Efficacy and safety of tangshen formula on patients with type 2 diabetic kidney
      disease: a multicenter double-blinded randomized placebo-controlled trial.
AB  - BACKGROUND: Persons with diabetes are at high risk of developing diabetic kidney
      disease (DKD), which is associated with high morbidity and mortality. Current
      drug therapies for DKD, such as angiotensin-converting enzyme inhibitors (ACEIs)
      and angiotensin receptor blockers (ARBs), are not entirely satisfactory. This
      study aimed to evaluate the additional benefit and safety of the Chinese herbal
      granule Tangshen Formula (TSF) in treating DKD. METHODS: The study was designed
      as a six-center randomized, double-blind, placebo-controlled trial. From April
      2007 through December 2009, 180 patients with DKD were enrolled. In addition to
      conventional treatment with ACEIs or ARBs, 122 participants were randomly
      assigned to receive TSF and 58 participants to receive placebo for 24 weeks.
      Primary outcome was urinary protein level, measured by urinary albumin excretion
      rate (UAER) for participants with microalbuminuria, 24-hour urinary protein (24h
      UP) for participants with macroalbuminuria. Secondary outcomes included renal
      function, serum lipids, quality of life, symptoms, and adverse events. FINDINGS:
      After 24 weeks of treatment, no statistically significant difference in UAER (TSF
      -19.53 MUg/min compared with placebo -7.01 MUg/min, with a mean difference of 
      12.52 MUg/min; 95%CI, -68.67 to 43.63, P = 0.696) was found between TSF and
      placebo groups. However, TSF displayed a statistically significant decrease in
      24h UP (TSF-0.21 g compared with placebo 0.36 g, with a mean difference of 
      0.57g; 95%CI, -1.05 to -0.09, P = 0.024). Estimated glomerular filtration rate
      (eGFR) was improved in both patients with microalbuminuria and macroalbuminuria,
      with a mean difference of 15.51 ml/min/1.73 m2 (95%CI, 3.71 to 27.31), 9.01
      ml/min/1.73 m2 (95%CI, -0.10 to 18.13), respectively. Other secondary outcomes
      showed no statistically significant difference between groups or in the incidence
      of adverse events. CONCLUSIONS: Based on conventional treatments, TSF appears to
      provide additional benefits compared with placebo in decreasing proteinuria and
      improving eGFR in DKD patients with macroalbuminuria. Nevertheless, further study
      is needed to evaluate TSF treating patients with microalbuminuria. TRIAL
      REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TRC-10000843.

PMID- 25938779
TI  - A memory-efficient deterministic finite automaton-based bit-split string matching
      scheme using pattern uniqueness in deep packet inspection.
AB  - This paper proposes a memory-efficient bit-split string matching scheme for deep
      packet inspection (DPI). When the number of target patterns becomes large, the
      memory requirements of the string matching engine become a critical issue. The
      proposed string matching scheme reduces the memory requirements using the
      uniqueness of the target patterns in the deterministic finite automaton (DFA)
      based bit-split string matching. The pattern grouping extracts a set of unique
      patterns from the target patterns. In the set of unique patterns, a pattern is
      not the suffix of any other patterns. Therefore, in the DFA constructed with the
      set of unique patterns, when only one pattern can be matched in an output state.
      In the bit-split string matching, multiple finite-state machine (FSM) tiles with
      several input bit groups are adopted in order to reduce the number of stored
      state transitions. However, the memory requirements for storing the matching
      vectors can be large because each bit in the matching vector is used to identify
      whether its own pattern is matched or not. In our research, the proposed pattern
      grouping is applied to the multiple FSM tiles in the bit-split string matching.
      For the set of unique patterns, the memory-based bit-split string matching engine
      stores only the pattern match index for each state to indicate the match with its
      own unique pattern. Therefore, the memory requirements are significantly
      decreased by not storing the matching vectors in the string matchers for the set
      of unique patterns. The experimental results show that the proposed string
      matching scheme can reduce the storage cost significantly compared to the
      previous bit-split string matching methods. 

PMID- 25938780
TI  - Autoantibodies in systemic autoimmune diseases: specificity and pathogenicity.
AB  - In this Review we focus on the initiation of autoantibody production and
      autoantibody pathogenicity, with a special emphasis on the targeted antigens.
      Release of intracellular antigens due to excessive cell death or to ineffective
      clearance of apoptotic debris, modification of self-antigens during inflammatory
      responses, and molecular mimicry contribute to the initiation of autoantibody
      production. We hypothesize that those autoreactive B cells that survive and
      produce pathogenic autoantibodies have specificity for self-antigens that are TLR
      ligands. Such B cells experience both B cell receptor (BCR) activation and TLR
      engagement, leading to an escape from tolerance. Moreover, the autoantibodies
      they produce form immune complexes that can activate myeloid cells and thereby
      establish the proinflammatory milieu that further negates tolerance mechanisms of
      both B and T cells. 

PMID- 25938781
TI  - Checkpoints that control B cell development.
AB  - B cells differentiate from pluripotent hematopoietic stem cells (pHSCs) in a
      series of distinct stages. During early embryonic development, pHSCs migrate into
      the fetal liver, where they develop and mature to B cells in a transient wave,
      which preferentially populates epithelia and lung as well as gut-associated
      lymphoid tissues. This is followed by continuous B cell development throughout
      life in the bone marrow to immature B cells that migrate to secondary lymphoid
      tissues, where they mature. At early stages of development, before B cell
      maturation, the gene loci encoding the heavy and light chains of immunoglobulin
      that determine the B cell receptor composition undergo stepwise rearrangements of
      variable region-encoding gene segments. Throughout life, these gene
      rearrangements continuously generate B cell repertoires capable of recognizing a
      plethora of self-antigens and non-self-antigens. The microenvironment in which
      these B cell repertoires develop provide signaling molecules that play critical
      roles in promoting gene rearrangements, proliferation, survival, or apoptosis,
      and that help to distinguish self-reactive from non-self-reactive B cells at four
      distinct checkpoints. This refinement of the B cell repertoire directly
      contributes to immunity, and defects in the process contribute to autoimmune
      disease. 

PMID- 25938782
TI  - BCL11A deletions result in fetal hemoglobin persistence and neurodevelopmental
      alterations.
AB  - A transition from fetal hemoglobin (HbF) to adult hemoglobin (HbA) normally
      occurs within a few months after birth. Increased production of HbF after this
      period of infancy ameliorates clinical symptoms of the major disorders of adult
      beta-hemoglobin: beta-thalassemia and sickle cell disease. The transcription
      factor BCL11A silences HbF and has been an attractive therapeutic target for
      increasing HbF levels; however, it is not clear to what extent BCL11A inhibits
      HbF production or mediates other developmental functions in humans. Here, we
      identified and characterized 3 patients with rare microdeletions of 2p15-p16.1
      who presented with an autism spectrum disorder and developmental delay. Moreover,
      these patients all exhibited substantial persistence of HbF but otherwise
      retained apparently normal hematologic and immunologic function. Of the genes
      within 2p15-p16.1, only BCL11A was commonly deleted in all of the patients.
      Evaluation of gene expression data sets from developing and adult human brains
      revealed that BCL11A expression patterns are similar to other genes associated
      with neurodevelopmental disorders. Additionally, common SNPs within the second
      intron of BCL11A are strongly associated with schizophrenia. Together, the study
      of these rare patients and orthogonal genetic data demonstrates that BCL11A plays
      a central role in silencing HbF in humans and implicates BCL11A as an important
      factor for neurodevelopment. 

PMID- 25938783
TI  - Prevention of PKG1alpha oxidation augments cardioprotection in the stressed
      heart.
AB  - The cGMP-dependent protein kinase-1alpha (PKG1alpha) transduces NO and
      natriuretic peptide signaling; therefore, PKG1alpha activation can benefit the
      failing heart. Disease modifiers such as oxidative stress may depress the
      efficacy of PKG1alpha pathway activation and underlie variable clinical results.
      PKG1alpha can also be directly oxidized, forming a disulfide bond between
      homodimer subunits at cysteine 42 to enhance oxidant-stimulated vasorelaxation;
      however, the impact of PKG1alpha oxidation on myocardial regulation is unknown.
      Here, we demonstrated that PKG1alpha is oxidized in both patients with heart
      disease and in rodent disease models. Moreover, this oxidation contributed to
      adverse heart remodeling following sustained pressure overload or Gq agonist
      stimulation. Compared with control hearts and myocytes, those expressing a redox
      dead protein (PKG1alpha(C42S)) better adapted to cardiac stresses at functional,
      histological, and molecular levels. Redox-dependent changes in PKG1alpha altered
      intracellular translocation, with the activated, oxidized form solely located in
      the cytosol, whereas reduced PKG1alpha(C42S) translocated to and remained at the
      outer plasma membrane. This altered PKG1alpha localization enhanced suppression
      of transient receptor potential channel 6 (TRPC6), thereby potentiating
      antihypertrophic signaling. Together, these results demonstrate that myocardial
      PKG1alpha oxidation prevents a beneficial response to pathological stress, may
      explain variable responses to PKG1alpha pathway stimulation in heart disease, and
      indicate that maintaining PKG1alpha in its reduced form may optimize its
      intrinsic cardioprotective properties.

PMID- 25938784
TI  - Hyperglycemia modulates extracellular amyloid-beta concentrations and neuronal
      activity in vivo.
AB  - Epidemiological studies show that patients with type 2 diabetes (T2DM) and
      individuals with a diabetes-independent elevation in blood glucose have an
      increased risk for developing dementia, specifically dementia due to Alzheimer's
      disease (AD). These observations suggest that abnormal glucose metabolism likely
      plays a role in some aspects of AD pathogenesis, leading us to investigate the
      link between aberrant glucose metabolism, T2DM, and AD in murine models. Here, we
      combined two techniques - glucose clamps and in vivo microdialysis - as a means
      to dynamically modulate blood glucose levels in awake, freely moving mice while
      measuring real-time changes in amyloid-beta (Abeta), glucose, and lactate within
      the hippocampal interstitial fluid (ISF). In a murine model of AD, induction of
      acute hyperglycemia in young animals increased ISF Abeta production and ISF
      lactate, which serves as a marker of neuronal activity. These effects were
      exacerbated in aged AD mice with marked Abeta plaque pathology. Inward
      rectifying, ATP-sensitive potassium (K(ATP)) channels mediated the response to
      elevated glucose levels, as pharmacological manipulation of K(ATP) channels in
      the hippocampus altered both ISF Abeta levels and neuronal activity. Taken
      together, these results suggest that K(ATP) channel activation mediates the
      response of hippocampal neurons to hyperglycemia by coupling metabolism with
      neuronal activity and ISF Abeta levels.

PMID- 25938785
TI  - MHCII-independent CD4+ T cells protect injured CNS neurons via IL-4.

PMID- 25938787
TI  - Suppression of NLRX1 in chronic obstructive pulmonary disease.
AB  - Cigarette smoke (CS) and viruses promote the inflammation and remodeling
      associated with chronic obstructive pulmonary disease (COPD). The MAVS/RIG-I-like
      helicase (MAVS/RLH) pathway and inflammasome-dependent innate immune pathways are
      important mediators of these responses. At baseline, the MAVS/RLH pathway is
      suppressed, and this inhibition must be reversed to engender tissue effects;
      however, the mechanisms that mediate activation and repression of the pathway
      have not been defined. In addition, the regulation and contribution of MAVS/RLH
      signaling in CS-induced inflammation and remodeling responses and in the
      development of human COPD remain unaddressed. Here, we demonstrate that
      expression of NLRX1, which inhibits the MAVS/RLH pathway and regulates other
      innate immune responses, was markedly decreased in 3 independent cohorts of COPD
      patients. NLRX1 suppression correlated directly with disease severity and
      inversely with pulmonary function, quality of life, and prognosis. In murine
      models, CS inhibited NLRX1, and CS-induced inflammation, alveolar destruction,
      protease induction, structural cell apoptosis, and inflammasome activation were
      augmented in NLRX1-deficient animals. Conversely, MAVS deficiency abrogated this
      CS-induced inflammation and remodeling. Restoration of NLRX1 in CS-exposed
      animals ameliorated alveolar destruction. These data support a model in which CS
      dependent NLRX1 inhibition facilitates MAVS/RHL activation and subsequent
      inflammation, remodeling, protease, cell death, and inflammasome responses. 

PMID- 25938786
TI  - Nanoparticulate STING agonists are potent lymph node-targeted vaccine adjuvants.
AB  - Cyclic dinucleotides (CDNs) are agonists of stimulator of IFN genes (STING) and
      have potential as vaccine adjuvants. However, cyclic di-GMP (cdGMP) injected s.c.
      shows minimal uptake into lymphatics/draining lymph nodes (dLNs) and instead is
      rapidly distributed to the bloodstream, leading to systemic inflammation. Here,
      we encapsulated cdGMP within PEGylated lipid nanoparticles (NP-cdGMP) to redirect
      this adjuvant to dLNs. Compared with unformulated CDNs, encapsulation blocked
      systemic dissemination and markedly enhanced dLN accumulation in murine models.
      Delivery of NP-cdGMP increased CD8+ T cell responses primed by peptide vaccines
      and enhanced therapeutic antitumor immunity. A combination of a poorly
      immunogenic liposomal HIV gp41 peptide antigen and NP-cdGMP robustly induced type
      I IFN in dLNs, induced a greater expansion of vaccine-specific CD4+ T cells, and
      greatly increased germinal center B cell differentiation in dLNs compared with a
      combination of liposomal HIV gp41 and soluble CDN. Further, NP-cdGMP promoted
      durable antibody titers that were substantially higher than those promoted by the
      well-studied TLR agonist monophosphoryl lipid A and comparable to a much larger
      dose of unformulated cdGMP, without the systemic toxicity of the latter. These
      results demonstrate that nanoparticulate delivery safely targets CDNs to the dLNs
      and enhances the efficacy of this adjuvant. Moreover, this approach can be
      broadly applied to other small-molecule immunomodulators of interest for vaccines
      and immunotherapy. 

PMID- 25938789
TI  - Modified electrodes used for electrochemical detection of metal ions in
      environmental analysis.
AB  - Heavy metal pollution is one of the most serious environmental problems, and
      regulations are becoming stricter. Many efforts have been made to develop sensors
      for monitoring heavy metals in the environment. This review aims at presenting
      the different label-free strategies used to develop electrochemical sensors for
      the detection of heavy metals such as lead, cadmium, mercury, arsenic etc. The
      first part of this review will be dedicated to stripping voltammetry techniques,
      on unmodified electrodes (mercury, bismuth or noble metals in the bulk form), or
      electrodes modified at their surface by nanoparticles, nanostructures (CNT,
      graphene) or other innovative materials such as boron-doped diamond. The second
      part will be dedicated to chemically modified electrodes especially those with
      conducting polymers. The last part of this review will focus on bio-modified
      electrodes. Special attention will be paid to strategies using biomolecules (DNA,
      peptide or proteins), enzymes or whole cells. 

PMID- 25938790
TI  - Practicing psychotherapists are more skilled at downregulating negative emotions
      than other professionals.
AB  - Laypeople and psychotherapists alike tend to assume that psychotherapists are
      more effective than the average population in regulating negative emotions. Being
      receptive to patients' distress and being able to downregulate negative emotions
      are important skills for psychotherapists to provide effective help and sustain
      their own well-being. We investigated whether psychotherapists react to negative
      material differently and downregulate emotions more effectively than individuals
      working in other, nontherapeutic, professions. Practicing psychotherapists (n =
      21) and a control group of nontherapists (n = 18) were exposed to pictures
      designed to elicit negative emotions in varying intensities and were asked to
      rate their emotional response, first after viewing them naturally and then after
      choosing and applying one of two given regulation strategies (i.e., distraction
      and reappraisal). Both groups responded similarly in terms of emotional
      reactivity and strategy choices, but psychotherapists were more effective than
      nontherapists in reducing their emotional response after applying emotion
      regulation strategies. We suggest that psychotherapists' comparable emotional
      reactivity and more effective emotion regulation make them well prepared to
      provide effective help to patients and safeguard their own well-being.

PMID- 25938788
TI  - STIM1 controls T cell-mediated immune regulation and inflammation in chronic
      infection.
AB  - Chronic infections induce a complex immune response that controls pathogen
      replication, but also causes pathology due to sustained inflammation. Ca2+ influx
      mediates T cell function and immunity to infection, and patients with inherited
      mutations in the gene encoding the Ca2+ channel ORAI1 or its activator stromal
      interaction molecule 1 (STIM1) are immunodeficient and prone to chronic infection
      by various pathogens, including Mycobacterium tuberculosis (Mtb). Here, we
      demonstrate that STIM1 is required for T cell-mediated immune regulation during
      chronic Mtb infection. Compared with WT animals, mice with T cell-specific Stim1
      deletion died prematurely during the chronic phase of infection and had increased
      bacterial burdens and severe pulmonary inflammation, with increased myeloid and
      lymphoid cell infiltration. Although STIM1-deficient T cells exhibited markedly
      reduced IFN-gamma production during the early phase of Mtb infection, bacterial
      growth was not immediately exacerbated. During the chronic phase, however, STIM1
      deficient T cells displayed enhanced IFN-gamma production in response to elevated
      levels of IL-12 and IL-18. The lack of STIM1 in T cells was associated with
      impaired activation-induced cell death upon repeated TCR engagement and pulmonary
      lymphocytosis and hyperinflammation in Mtb-infected mice. Chronically Mtb
      infected, STIM1-deficient mice had reduced levels of inducible regulatory T cells
      (iTregs) due to a T cell-intrinsic requirement for STIM1 in iTreg differentiation
      and excessive production of IFN-gamma and IL-12, which suppress iTreg
      differentiation and maintenance. Thus, STIM1 controls multiple aspects of T cell
      mediated immune regulation to limit injurious inflammation during chronic
      infection. 

PMID- 25938792
TI  - Diagnostic Role of Head-Bending and Lying-Down Tests in Lateral Canal Benign
      Paroxysmal Positional Vertigo.
AB  - OBJECTIVES: To compare the diagnostic value of the head-bending test (HBT), lying
      down positioning test (LDPT) and patient's report to identify the affected canal
      in video-nystagmographically (VNG) confirmed patients with lateral canal benign
      paroxysmal positional vertigo (LC-BPPV). STUDY DESIGN: Case series with chart
      review. SETTING: Head-bending, lying-down positioning and the head-roll maneuver
      (HRM) under VNG guidance. The data were collected in a referral community
      hospital. PATIENTS: Seventy-eight patients (32 apogeotropic and 46 geotropic
      nystagmus) with LC-BPPV who had been recruited between 2009 and 2013 were
      enrolled in the study. MAIN OUTCOME MEASURES: Patients were tested with the HRM
      and then were asked about subjectively worse side. Later, they were subjected to
      HBT when sitting and the LDPT. The results were compared and studied with the 1
      way ANOVA and chi-square tests. Statistical significance was set at p < 0.05.
      RESULTS: Affected side was identified by HRM in 75% of patients with apogeotropic
      nystagmus and 95.6% of patients with geotropic nystagmus. Approximately 65.6% of
      patients with apogeotropic and 52% of patients with geotropic nystagmus had
      nystagmus during LDPT. However, its comparability with HRM was low. However,
      treatment plan based on LDPT results alone provided relief of symptoms in
      additional 12.5% of patients with apogeotropic and in 2.2% of patients with
      geotropic nystagmus. Approximately 63% of patients with apogeotropic and 56% of
      patients with geotropic nystagmus were able to tell the worse side. Nystagmus
      comparable with HRM during HBT was low and not diagnostic. CONCLUSION: HRM has
      the greatest diagnostic value of positioning tests in LC-BPPV in this study. LDPT
      provides some contribution in the diagnosis of LC-BPPV but much less than HRM.
      Patients' subjective feeling of vertigo was also a useful test. However, HBT was
      not as sensitive as other measures in uncertain cases.

PMID- 25938793
TI  - Preparation and Evaluation of Hybrid Composites of Chemical Fuel and Multi-walled
      Carbon Nanotubes in the Study of Thermopower Waves.
AB  - When a chemical fuel at a certain position in a hybrid composite of the fuel and
      a micro/nanostructured material is ignited, chemical combustion occurs along the
      interface between the fuel and core materials. Simultaneously, dynamic changes in
      thermal and chemical potentials across the micro/nanostructured materials result
      in concomitant electrical energy generation induced by charge transfer in the
      form of a high-output voltage pulse. We demonstrate the entire procedure of a
      thermopower wave experiment, from synthesis to evaluation. Thermal chemical vapor
      deposition and the wet impregnation process are respectively employed for the
      synthesis of a multi-walled carbon nanotube array and a hybrid composite of
      picric acid/sodium azide/multi-walled carbon nanotubes. The prepared hybrid
      composites are used to fabricate a thermopower wave generator with connecting
      electrodes. The combustion of the hybrid composite is initiated by laser heating
      or Joule-heating, and the corresponding combustion propagation, direct electrical
      energy generation, and real-time temperature changes are measured using a high
      speed microscopy system, an oscilloscope, and an optical pyrometer, respectively.
      Furthermore, the crucial strategies to be adopted in the synthesis of hybrid
      composite and initiation of their combustion that enhance the overall thermopower
      wave energy transfer are proposed. 

PMID- 25938794
TI  - What impact does 'conventional' economic evaluation have on patient access to new
      orphan medicines? A comparative study of their reimbursement in Australia (2005
      2012).
AB  - BACKGROUND: Orphan medicines used to treat patients with rare diseases often come
      at high costs with lower levels of clinical evidence. We compared the likelihood
      and timeliness of reimbursement for orphan medicines with non-orphan medicines in
      Australia between 2005 and 2012. METHODS: We developed two key assessment metrics
      to compare submissions and outcomes for new orphan medicines with those for new
      non-orphan medicines, viz., the likelihood of submissions being recommended by
      the Pharmaceutical Benefits Advisory Committee (PBAC) (success rate) and the time
      from Therapeutic Goods Administration registration to reimbursement (overall
      timeliness). RESULTS: Thirty eight out of 95 outcomes for orphan medicines (40%)
      received a PBAC recommendation compared to 257/481 (53%) for non-orphan medicines
      (p = 0.17). The PBAC recommendations that resulted in listings were comparable
      between the orphan and non-orphan categories (33/38 [87%] vs 218/257 [85%],
      respectively, p = 0.74). CONCLUSION: The results suggested orphan medicines were
      not accorded any special status for reimbursement.

PMID- 25938795
TI  - Is anyone around me using condoms? Site-specific condom-use norms and their
      potential impact on condomless sex across various gay venues and websites in The
      Netherlands.
AB  - OBJECTIVE: To investigate site-specific condom-use norms as assumed by visitors
      of gay venues and websites across The Netherlands and their association with
      men's own use of condoms. METHODS: In 2010, men who have sex with men (MSM)
      visiting 18 sex venues (e.g., saunas), 30 nonsex venues (e.g., bars), 6 dating
      websites, and 2 social network websites completed an on-site questionnaire
      measuring 2 site-specific norms concerning anal sex: descriptive (assumed condom
      use of others at venue or website) and injunctive (assumed approval of condom use
      by others at venue or website). We measured the association between assumed
      descriptive norms and own use of condoms using logistic regression. RESULTS:
      Among 2,376 participants (median age = 30 years; IQR = 22-43), 62% (n = 1,483)
      assumed that other visitors would not use condoms. Among men self-reporting on
      their own use of condoms, 22% (318/1,421) reported condomless anal sex. Men at
      nonsex venues assumed other visitors would use condoms more often and approved of
      using them more often compared to men at sex venues. At all sites
      (venues/websites), men who assumed that others did not use condoms were more
      likely to have condomless sex themselves. CONCLUSIONS: At gay sites across The
      Netherlands, more than half of MSM believed visitors of these sites would not use
      condoms during anal sex. The perception that others would not use condoms was
      associated with less own condom use. HIV prevention should address problematic on
      site condom-use norms, as they play a role in influencing sexual behavior between
      men that meet at these sites.

PMID- 25938796
TI  - Light-induced c-Fos expression in the SCN and behavioural phase shifts of
      Djungarian hamsters with a delayed activity onset.
AB  - C-Fos expression in the suprachiasmatic nucleus (SCN) and phase shifts of the
      activity rhythm following photic stimulation were investigated in Djungarian
      hamsters (Phodopus sungorus) of two different circadian phenotypes. Wild-type
      (WT) hamsters display robust daily patterns of locomotor activity according to
      the light/dark conditions. Hamsters of the DAO (delayed activity onset)
      phenotype, however, progressively delay the activity onset, whereas activity
      offset remains coupled to "light-on". Although the exact reason for the delayed
      activity onset is not yet clarified, it is connected with a disturbed interaction
      between the light/dark cycle and the circadian clock. The aim was to test the
      link between photoreception and the behavioral output of the circadian system in
      hamsters of both phenotypes, to get further insight in the underlying mechanism
      of the DAO phenomenon. Animals were exposed to short light pulses at different
      times during the dark period to analyze phase shifts of the activity rhythm and
      expression of Fos protein in the SCN. The results indicate that the
      photosensitive phase in DAO hamsters is shifted like the activity onset. Also,
      phase shifts were significantly smaller in DAO hamsters. At the same time, levels
      of Fos expression did not differ between phenotypes regarding the circadian
      phase. The results provide evidence that the shifted photosensitivity of the
      circadian system in DAO hamsters does not differ from that of WT animals, and
      lead us to conclude that processes within the SCN that enable light information
      to reset the circadian pacemaker might offer an explanation for the DAO
      phenomenon. 

PMID- 25938797
TI  - Quantitative study of the photothermal properties of metallic nanowire networks.
AB  - In this article, we present a comprehensive investigation of the photothermal
      properties of plasmonic nanowire networks. We measure the local steady-state
      temperature increase, heat source density, and absorption in Ag, Au, and Ni
      metallic nanowire networks under optical illumination. This allows direct
      experimental confirmation of increased heat generation at the junction between
      two metallic nanowires and stacking-dependent absorption of polarized light. Due
      to thermal collective effects, the local temperature distribution in a network is
      shown to be completely delocalized on a micrometer scale, despite the nanoscale
      features in the heat source density. Comparison of the experimental temperature
      profile with numerical simulation allows an upper limit for the effective thermal
      conductivity of a Ag nanowire network to be established at 43 Wm(-1) K(-1) (0.1
      kappabulk). 

PMID- 25938798
TI  - Invasive Pneumococcal Disease Following the Introduction of 13-Valent Conjugate
      Vaccine in Children in New York City From 2007 to 2012.
AB  - IMPORTANCE: Invasive pneumococcal disease (IPD) is a leading cause of pneumonia,
      meningitis, and bacteremia in children. In March 2010, a 13-valent pneumococcal
      conjugate vaccine (PCV13) was introduced to the routine childhood immunization
      schedule. The PCV13 contains 6 serotypes not included in the previously
      recommended 7-valent pneumococcal conjugate vaccine, including serotype 19A, the
      predominant cause of IPD prior to the introduction of PCV13. OBJECTIVES: To
      describe changes in the epidemiology and incidence of IPD in children younger
      than 5 years in New York City (NYC) after the introduction of PCV13 and assess
      PCV13 coverage in NYC. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis
      of population-based IPD surveillance data of the general population residing in
      NYC between January 1, 2007, and December 31, 2012. Invasive pneumococcal disease
      cases were identified by laboratory reporting of positive pneumococcal cultures
      from a normally sterile body site in NYC residents younger than 5 years. Isolates
      were serotyped. Participants included 468 cases younger than 5 years with IPD
      reported through routine surveillance to the NYC Department of Health and Mental
      Hygiene. MAIN OUTCOMES AND MEASURES: Absolute differences and percentage changes
      in IPD incidence before and after the introduction of PCV13 by serotype grouping,
      age, and race/ethnicity. The number of PCV13 doses administered to children
      younger than 5 years was calculated using the NYC immunization information
      system. RESULTS: There were 468 IPD cases from 2007 to 2012. The incidence of IPD
      decreased by 69.6% (95% CI, -79.3% to -55.5%) from 21.0 cases per 100 000 (2007
      2009 mean) pre-PCV13 to 6.4 cases per 100 000 (2011-2012 mean) post-PCV13.
      Estimates of disease caused by serotypes included in the PCV13 decreased by 82.5%
      (95% CI, -90.0% to -69.3%), including a 79.7% reduction in serotype 19A (95% CI, 
      89.0% to -62.4%). Reductions in IPD incidence were seen in all age groups, with
      the largest reduction in children younger than 12 months (80.4%; P = .005).
      Incidence decreased significantly in all racial/ethnic groups. The percentage of
      children younger than 5 years in NYC with 1 or more doses of PCV13 increased from
      47.8% in 2010 to 89.8% in 2012. CONCLUSIONS AND RELEVANCE: The incidence of IPD
      in NYC children younger than 5 years and, particularly, the incidence of IPD
      caused by serotype 19A decreased dramatically following the introduction of
      PCV13, with reductions among all age and racial/ethnic groups. This represents a
      significant achievement for public health immunization programs and underscores
      the importance of achieving high immunization coverage.

PMID- 25938799
TI  - Kinetic Differences and Synergistic Antiviral Effects Between Type I and Type III
      Interferon Signaling Indicate Pathway Independence.
AB  - The spread of acute respiratory viral infections is controlled by type I and III
      interferon (IFN) signaling. While the mechanisms of type I IFN signaling have
      been studied in detail, features that distinguish type III IFN signaling remain
      poorly understood. Type III IFNs play an essential role in limiting infections of
      intestinal and respiratory epithelial surfaces; however, type III IFNs have been
      shown to activate similar genes to type I IFNs, raising the question of how these
      IFNs differ and their signals interact. We measured the kinetics of type I and
      III IFN activation, functional stability, and downstream antiviral responses on
      A549 human lung epithelial cells. Similar kinetics were found for transcriptional
      upregulation and secretion of type I and III IFNs in response to infection by an
      RNA virus, peaking at 12 h postinfection, and both protein types had similar
      stabilities with functional half-lives extending beyond 2 days. Both IFNs
      activated potent cellular antiviral responses; however, responses to type III
      IFNs were delayed by 2-6 h relative to type I IFN responses. Combined treatments
      with type I and III IFNs produced enhanced antiviral effects, and quantitative
      analysis of these data with a Bliss interaction model provides evidence for
      independence of type I and III IFN downstream signaling pathways. This novel
      synergistic interaction has therapeutic implications for treatment of respiratory
      virus infections. 

PMID- 25938800
TI  - Direct hydroxylation of benzene to phenol using hydrogen peroxide catalyzed by
      nickel complexes supported by pyridylalkylamine ligands.
AB  - Selective hydroxylation of benzene to phenol has been achieved using H2O2 in the
      presence of a catalytic amount of the nickel complex [Ni(II)(tepa)](2+) (2) (tepa
      = tris[2-(pyridin-2-yl)ethyl]amine) at 60  degrees C. The maximum yield of phenol
      was 21% based on benzene without the formation of quinone or diphenol. In an
      endurance test of the catalyst, complex 2 showed a turnover number (TON) of 749,
      which is the highest value reported to date for molecular catalysts in benzene
      hydroxylation with H2O2. When toluene was employed as a substrate instead of
      benzene, cresol was obtained as the major product with 90% selectivity. When
      H2(18)O2 was utilized as the oxidant, (18)O-labeled phenol was predominantly
      obtained. The reaction rate for fully deuterated benzene was nearly identical to
      that of benzene (kinetic isotope effect = 1.0). On the basis of these results,
      the reaction mechanism is discussed. 

PMID- 25938801
TI  - Association of a Novel ACTA1 Mutation With a Dominant Progressive Scapuloperoneal
      Myopathy in an Extended Family.
AB  - IMPORTANCE: New genomic strategies can now be applied to identify a diagnosis in
      patients and families with previously undiagnosed rare genetic conditions. The
      large family evaluated in the present study was described in 1966 and now expands
      the phenotype of a known neuromuscular gene. OBJECTIVE: To determine the genetic
      cause of a slowly progressive, autosomal dominant, scapuloperoneal neuromuscular
      disorder by using linkage and exome sequencing. DESIGN, SETTING, AND
      PARTICIPANTS: Fourteen affected individuals in a 6-generation family with a
      progressive scapuloperoneal disorder were evaluated. Participants were examined
      at pediatric, neuromuscular, and research clinics from March 1, 2005, to May 31,
      2014. Exome and linkage were performed in genetics laboratories of research
      institutions. MAIN OUTCOMES AND MEASURES: Examination and evaluation by magnetic
      resonance imaging, ultrasonography, electrodiagnostic studies, and muscle
      biopsies (n = 3). Genetic analysis included linkage analysis (n = 17) with exome
      sequencing (n = 7). RESULTS: Clinical findings included progressive muscle
      weakness in an initially scapuloperoneal and distal distribution, including wrist
      extensor weakness, finger and foot drop, scapular winging, mild facial weakness,
      Achilles tendon contractures, and diminished or absent deep tendon reflexes. Both
      age at onset and progression of the disease showed clinical variability within
      the family. Muscle biopsy specimens demonstrated type I fiber atrophy and
      trabeculated fibers without nemaline rods. Analysis of exome sequences within the
      linkage region (4.8 megabases) revealed missense mutation c.591C>A p.Glu197Asp in
      a highly conserved residue in exon 4 of ACTA1. The mutation cosegregated with
      disease in all tested individuals and was not present in unaffected individuals.
      CONCLUSIONS AND RELEVANCE: This family defines a new scapuloperoneal phenotype
      associated with an ACTA1 mutation. A highly conserved protein, ACTA1 is
      implicated in multiple muscle diseases, including nemaline myopathy, actin
      aggregate myopathy, fiber-type disproportion, and rod-core myopathy. To our
      knowledge, mutations in Glu197 have not been reported previously. This residue is
      highly conserved and located in an exposed position in the protein; the mutation
      affects the intermolecular and intramolecular electrostatic interactions as shown
      by structural modeling. The mutation in this residue does not appear to lead to
      rod formation or actin accumulation in vitro or in vivo, suggesting a different
      molecular mechanism from that of other ACTA1 diseases.

PMID- 25938803
TI  - Accountable care organizations and evidence-based payment reform.

PMID- 25938802
TI  - Molecular Recognition of Human Liver Cancer Cells Using DNA Aptamers Generated
      via Cell-SELEX.
AB  - Most clinical cases of liver cancer cannot be diagnosed until they have evolved
      to an advanced stage, thus resulting in high mortality. It is well recognized
      that the implementation of early detection methods and the development of
      targeted therapies for liver cancer are essential to reducing the high mortality
      rates associated with this disease. To achieve these goals, molecular probes
      capable of recognizing liver cancer cell-specific targets are needed. Here we
      describe a panel of aptamers able to distinguish hepatocarcinoma from normal
      liver cells. The aptamers, which were selected by cell-based SELEX (Systematic
      Evolution of Ligands by Exponential Enrichment), have Kd values in the range of
      64-349 nM toward the target human hepatoma cell HepG2, and also recognize ovarian
      cancer cells and lung adenocarcinoma. The proteinase treatment experiment
      indicated that all aptamers could recognize target HepG2 cells through surface
      proteins. This outcome suggested that these aptamers could be used as potential
      probes for further research in cancer studies, such as developing early detection
      assays, targeted therapies, and imaging agents, as well as for the investigation
      of common membrane proteins in these distinguishable cancers. 

PMID- 25938804
TI  - Genetic barcoding with fluorescent proteins for multiplexed applications.
AB  - Fluorescent proteins, fluorescent dyes and fluorophores in general have
      revolutionized the field of molecular cell biology. In particular, the discovery
      of fluorescent proteins and their genes have enabled the engineering of protein
      fusions for localization, the analysis of transcriptional activation and
      translation of proteins of interest, or the general tracking of individual cells
      and cell populations. The use of fluorescent protein genes in combination with
      retroviral technology has further allowed the expression of these proteins in
      mammalian cells in a stable and reliable manner. Shown here is how one can
      utilize these genes to give cells within a population of cells their own
      biosignature. As the biosignature is achieved with retroviral technology, cells
      are barcoded 'indefinitely'. As such, they can be individually tracked within a
      mixture of barcoded cells and utilized in more complex biological applications.
      The tracking of distinct populations in a mixture of cells is ideal for
      multiplexed applications such as discovery of drugs against a multitude of
      targets or the activation profile of different promoters. The protocol describes
      how to elegantly develop and amplify barcoded mammalian cells with distinct
      genetic fluorescent markers, and how to use several markers at once or one marker
      at different intensities. Finally, the protocol describes how the cells can be
      further utilized in combination with cell-based assays to increase the power of
      analysis through multiplexing.

PMID- 25938805
TI  - Effects of Sulfate during CO2 Attack on Portland Cement and Their Impacts on
      Mechanical Properties under Geologic CO2 Sequestration Conditions.
AB  - To investigate the effects of sulfate on CO2 attack on wellbore cement (i.e.,
      chemical and mechanical alterations) during geologic CO2 sequestration (GCS), we
      reacted cement samples in brine with 0.05 M sulfate and 0.4 M NaCl at 95  degrees
      C under 100 bar of either N2 or supercritical CO2. The results were compared to
      those obtained from systems without additional sulfate at the same temperature,
      pressure, salinity, and initial brine pHs. After 10 reaction days, chemical
      analyses using scanning electron microscopy with a backscattered electron
      detector (SEM-BSE) and inductively coupled plasma optical emission spectrometry
      (ICP-OES) showed that the CO2 attack in the presence of additional sulfate was
      much less severe than that in the system without additional sulfate. The results
      from three-point bending tests also indicated that sulfate significantly
      mitigated the deterioration of the cement's strength and elastic modulus. In all
      our systems, typical sulfate attacks on cement via formation of ettringite were
      not observed. The protective effects of sulfate on cement against CO2 attack
      resulted from sulfate adsorption, coating of CaSO4 on the CaCO3 grains in the
      carbonated layer, or both, which inhibited dissolution of CaCO3. Findings from
      this study provide new, important information for understanding the integrity of
      wellbores at GCS sites and thus promote safer GCS operations. 

PMID- 25938806
TI  - Extensive Identification of Bacterial Riboflavin Transporters and Their
      Distribution across Bacterial Species.
AB  - Riboflavin, the precursor for the cofactors flavin mononucleotide (FMN) and
      flavin adenine dinucleotide, is an essential metabolite in all organisms. While
      the functions for de novo riboflavin biosynthesis and riboflavin import may
      coexist in bacteria, the extent of this co-occurrence is undetermined. The RibM,
      RibN, RfuABCD and the energy-coupling factor-RibU bacterial riboflavin
      transporters have been experimentally characterized. In addition, ImpX, RfnT and
      RibXY are proposed as riboflavin transporters based on positional clustering with
      riboflavin biosynthetic pathway (RBP) genes or conservation of the FMN riboswitch
      regulatory element. Here, we searched for the FMN riboswitch in bacterial genomes
      to identify genes encoding riboflavin transporters and assessed their
      distribution among bacteria. Two new putative riboflavin transporters were
      identified: RibZ in Clostridium and RibV in Mesoplasma florum. Trans
      complementation of an Escherichia coli riboflavin auxotroph strain confirmed the
      riboflavin transport activity of RibZ from Clostridium difficile, RibXY from
      Chloroflexus aurantiacus, ImpX from Fusobacterium nucleatum and RfnT from
      Ochrobactrum anthropi. The analysis of the genomic distribution of all known
      bacterial riboflavin transporters revealed that most occur in species possessing
      the RBP and that some bacteria may even encode functional riboflavin transporters
      from two different families. Our results indicate that some species possess
      ancestral riboflavin transporters, while others possess transporters that appear
      to have evolved recently. Moreover, our data suggest that unidentified riboflavin
      transporters also exist. The present study doubles the number of experimentally
      characterized riboflavin transporters and suggests a specific, non-accessory role
      for these proteins in riboflavin-prototrophic bacteria. 

PMID- 25938807
TI  - Comparison of Azelnidipine and Trichlormethiazide in Japanese Type 2 Diabetic
      Patients with Hypertension: The COAT Randomized Controlled Trial.
AB  - OBJECTIVE: This study compared the efficacy and safety of azelnidipine with that
      of trichlormethiazide in Japanese type 2 diabetic patients with hypertension.
      METHODS: In a multicenter, open-label trial, 240 patients with adequately
      controlled diabetes (HbA1c <= 7.0%) under lifestyle modification and/or
      administration of hypoglycemic agents and inadequately controlled hypertension
      (systolic blood pressure [sBP] >= 130 mmHg or diastolic blood pressure [dBP] >=
      80 mmHg) who were being treated with olmesartan were enrolled. Participants were
      randomly assigned to an azelnidipine group or a trichlormethiazide group and were
      followed up for 48 weeks. Main outcome measure was the difference in the change
      in HbA1c levels from the baseline values at 48 weeks between these two groups.
      RESULTS: Of the 240 subjects that were enrolled, 209 subjects (azelnidipine
      group: 103 patients, trichlormethiazide group: 106 patients) completed this
      trial. At 48 weeks, the following changes were observed in the azelnidipine and
      trichlormethiazide groups, respectively: HbA1c levels, 0.19 +/- 0.52% and 0.19 +/
      0.54%; sBP/dBP, -10.7 +/- 9.6/-6.6 +/- 6.6 mmHg and -7.1 +/- 7.7/-3.3 +/- 6.1
      mmHg (P < 0.001 for both sBP and dBP). In both groups, dizziness (12 patients
      [11.7%] and 16 patients [15.1%]) and edema (16 patients [15.5%] and 7 patients
      [6.6%], P = 0.047) were observed during the 48-week follow-up period.
      CONCLUSIONS: Azelnidipine was more effective for controlling blood pressure than
      trichlormethiazide in Japanese type 2 diabetes patients, whereas
      trichlormethiazide was more effective for reducing albuminuria than azelnidipine.
      Both of these agents, however, similarly exacerbated glycemic control in type 2
      diabetic patients with hypertension. TRIAL REGISTRATION: UMIN 000006081.

PMID- 25938808
TI  - C-Peptide-based assessment of insulin secretion in the Zucker Fatty rat: a
      modelistic study.
AB  - A C-peptide-based assessment of beta-cell function was performed here in the
      Zucker fatty rat, a suitable animal model of human metabolic syndrome. To this
      aim, a 90-min intravenous glucose tolerance test (IVGTT) was performed in seven
      Zucker fatty rats (ZFR), 7-to-9 week-old, and seven age-matched Zucker lean rats
      (ZLR). The minimal model of C-peptide (CPMM), originally introduced for humans,
      was adapted to Zucker rats and then applied to interpret IVGTT data. For a
      comprehensive evaluation of glucose tolerance in ZFR, CPMM was applied in
      combination with the minimal model of glucose kinetics (GKMM). Our results showed
      that the present CPMM-based interpretation of data is able to: 1) provide a
      suitable fit of C-Peptide data; 2) achieve a satisfactory estimation of
      parameters of interest 3) quantify both insulin secretion by estimating the time
      course of pre-hepatic secretion rate, SR(t), and total insulin secretion, TIS,
      and pancreatic sensitivity by means of three specific indexes of beta-cell
      responsiveness to glucose stimulus (first-phase, F(1), second-phase, F(2), and
      steady-state, F(ss), never assessed in Zucker rats before; 4) detect the
      significant enhancement of insulin secretion in the ZFR, in face of a severe
      insulin-resistant state, previously observed only using a purely experimental
      approach. Thus, the methodology presented here represents a reliable tool to
      assess beta-cell function in the Zucker rat, and opens new possibilities for the
      quantification of further processes involved in glucose homeostasis such as the
      hepatic insulin degradation.

PMID- 25938809
TI  - Optimizing Attachment of Human Mesenchymal Stem Cells on Poly(epsilon
      caprolactone) Electrospun Yarns.
AB  - Research into biomaterials and tissue engineering often includes cell-based in
      vitro investigations, which require initial knowledge of the starting cell
      number. While researchers commonly reference their seeding density this does not
      necessarily indicate the actual number of cells that have adhered to the material
      in question. This is particularly the case for materials, or scaffolds, that do
      not cover the base of standard cell culture well plates. This study investigates
      the initial attachment of human mesenchymal stem cells seeded at a known number
      onto electrospun poly(epsilon-caprolactone) yarn after 4 hr in culture.
      Electrospun yarns were held within several different set-ups, including
      bioreactor vessels rotating at 9 rpm, cell culture inserts positioned in low
      binding well plates and polytetrafluoroethylene (PTFE) troughs placed within
      petri dishes. The latter two were subjected to either static conditions or
      positioned on a shaker plate (30 rpm). After 4 hr incubation at 37 (o)C, 5% CO2,
      the location of seeded cells was determined by cell DNA assay. Scaffolds were
      removed from their containers and placed in lysis buffer. The media fraction was
      similarly removed and centrifuged - the supernatant discarded and pellet broken
      up with lysis buffer. Lysis buffer was added to each receptacle, or well, and
      scraped to free any cells that may be present. The cell DNA assay determined the
      percentage of cells present within the scaffold, media and well fractions. Cell
      attachment was low for all experimental set-ups, with greatest attachment (30%)
      for yarns held within cell culture inserts and subjected to shaking motion. This
      study raises awareness to the actual number of cells attaching to scaffolds
      irrespective of the stated cell seeding density. 

PMID- 25938810
TI  - The influence of chronic stress on anxiety-like behavior and cognitive function
      in different human GFAP-ApoE transgenic adult male mice.
AB  - The apolipoprotein E (ApoE) E4 allele (ApoE4) is an important genetic risk factor
      for the pathogenesis of Alzheimer's disease (AD). In addition to genetic factors,
      environmental factors such as stress may play a critical role in AD pathogenesis.
      This study was designed to investigate the anxiety-like behavioral and cognitive
      changes in different human glial fibrillary acidic protein (GFAP)-ApoE transgenic
      adult male mice under chronic stress conditions. On the open field test, anxiety
      like behavior was increased in the non-stressed GFAP-ApoE4 transgenic mice
      relative to the corresponding GFAP-ApoE3 (ApoE E3 allele) mice. Anxiety-like
      behavior was increased in the stressed GFAP-ApoE3 mice relative to non-stressed
      GFAP-ApoE3 mice, but was unexpectedly decreased in the stressed GFAP-ApoE4 mice
      relative to non-stressed GFAP-ApoE4 mice. On the novel object recognition task,
      both GFAP-ApoE4 and GFAP-ApoE3 mice exhibited long-term non-spatial memory
      impairment after chronic stress. Interestingly, short-term non-spatial memory
      impairment (based on the novel object recognition task) was observed only in the
      stressed GFAP-ApoE4 male mice relative to non-stressed GFAP-ApoE4 transgenic
      mice. In addition, short-term spatial memory impairment was observed in the
      stressed GFAP-ApoE3 transgenic male mice relative to non-stressed GFAP-ApoE3
      transgenic male mice; however, short-term spatial memory performance of GFAP
      ApoE4 transgenic male mice was not reduced compared to non-stressed control mice
      based on the Y-maze task. In conclusion, our findings suggested that chronic
      stress affects anxiety-like behavior and spatial and non-spatial memory in GFAP
      ApoE transgenic mice in an ApoE isoform-dependent manner. 

PMID- 25938811
TI  - Organic-Inorganic Heterointerfaces for Ultrasensitive Detection of Ultraviolet
      Light.
AB  - The performance of graphene field-effect transistors is limited by the
      drastically reduced carrier mobility of graphene on silicon dioxide (SiO2)
      substrates. Here we demonstrate an ultrasensitive ultraviolet (UV)
      phototransistor featuring an organic self-assembled monolayer (SAM) sandwiched
      between an inorganic ZnO quantum dots decorated graphene channel and a
      conventional SiO2/Si substrate. Remarkably, the room-temperature mobility of the
      chemical-vapor-deposition grown graphene channel on the SAM is an order-of
      magnitude higher than on SiO2, thereby drastically reducing electron transit-time
      in the channel. The resulting recirculation of electrons (in the graphene
      channel) within the lifetime of the photogenerated holes (in the ZnO) increases
      the photoresponsivity and gain of the transistor to ~10(8) A/W and ~3 * 10(9),
      respectively with a UV to visible rejection ratio of ~10(3). Our UV photodetector
      device manufacturing is also compatible with current semiconductor processing,
      and suitable for large volume production. 

PMID- 25938812
TI  - The inclusion of Duroc breed in maternal line affects pork quality and fatty acid
      profile.
AB  - The aim of this study was to evaluate the effect of including different
      percentages of Duroc (D) breed in maternal line [Landrace (LR) * Large White
      (LW); LR * (LW * D); LR * D] and gender on meat quality and intramuscular (IMF)
      and subcutaneous (SCF) fatty acid composition. No significant differences were
      found among dam lines in ultimate pH, L* values and drip and cooking losses.
      There were higher percentages of saturated fatty acids in LR * D and LR * (LW *
      D) lines and higher percentages of polyunsaturated fatty acids in LR * LW line in
      IMF and SCF. Also, LR * D line produced pork with a lower Warner-Bratzler shear
      force values and higher IMF content and potential of lipid oxidation.
      Furthermore, the L*, a* and b* values and drip loss were greater in pork from
      entire males than females. The IMF and SCF of females were more monounsaturated
      and less polyunsaturated than those from entire males.

PMID- 25938813
TI  - Cooperative or Anticooperative: How Noncovalent Interactions Influence Each
      Other.
AB  - This computational study examines the key factors that control the structures and
      energetics of the coexistence of multiple noncovalent interactions. 4-Amino-2
      iodophenol is taken as a model that exhibits nine different kinds of noncovalent
      interactions, viz., cation-pi (CP), hydrogen bond (HB) through O (OHB), HB
      through N (NHB), halogen bond (XB), pi-pi (PP), metal ion-lone pair (ML) through
      O (OML), ML through N (NML), charge assisted hydrogen bond (CHB) through O
      (OCHB), and CHB through N (NCHB). Through all possible combinations of these
      noncovalent interactions, based on energy, geometry, charge, and atoms in
      molecules (AIM) analysis, we have systematically analyzed the cooperativity among
      40 ternary systems and 105 quaternary systems. We have observed that CP-HB, CP
      XB, CP-PP, HB-HB, HB-XB, HB-PP, HB-ML, HB-CHB, XB-PP, XB-ML, XB-CHB, PP-ML, and
      PP-OCHB can form cooperative ternary systems. While studying the quaternary
      systems, we have observed that HB, XB, and PP work together by enhancing each
      other's strength. The study highlights that the positively charged species
      enhances HB-HB and HB-PP interactions and forms cooperative HB-HB-CHB, HB-HB-ML,
      HB-PP-ML, and HB-PP-CHB systems. Surprisingly, OHB-OML-NML, OHB-OML-OCHB, OHB-OML
      NCHB, OHB-NML-OCHB, NHB-OML-NML, NHB-OML-NCHB, and NHB-NML-OCHB are also
      cooperative in nature despite the electrostatic repulsion between two positive
      charge species. The current study shows the widespread presence of cooperativity
      as well as anticooperativity in supramolecular assembles. 

PMID- 25938814
TI  - Feedback regulation between plasma membrane tension and membrane-bending proteins
      organizes cell polarity during leading edge formation.
AB  - Tension applied to the plasma membrane (PM) is a global mechanical parameter
      involved in cell migration. However, how membrane tension regulates actin
      assembly is unknown. Here, we demonstrate that FBP17, a membrane-bending protein
      and an activator of WASP/N-WASP-dependent actin nucleation, is a PM tension
      sensor involved in leading edge formation. In migrating cells, FBP17 localizes to
      short membrane invaginations at the leading edge, while diminishing from the cell
      rear in response to PM tension increase. Conversely, following reduced PM
      tension, FBP17 dots randomly distribute throughout the cell, correlating with
      loss of polarized actin assembly on PM tension reduction. Actin protrusive force
      is required for the polarized accumulation, indicating a role for FBP17-mediated
      activation of WASP/N-WASP in PM tension generation. In vitro experiments show
      that FBP17 membrane-bending activity depends on liposomal membrane tension. Thus,
      FBP17 is the local activator of actin polymerization that is inhibited by PM
      tension in the feedback loop that regulates cell migration. 

PMID- 25938816
TI  - [Nora's Lesion: A Rare Differential Diagnosis for Benign Peripheral Bone
      Tumours].
AB  - We report on a bizarre parosteal osteochondromatous proliferation (BPOP), also
      known as Nora's lesion, in a 43-year-old female patient. 

PMID- 25938815
TI  - An instructive role for C. elegans E-cadherin in translating cell contact cues
      into cortical polarity.
AB  - Cell contacts provide spatial cues that polarize early embryos and epithelial
      cells. The homophilic adhesion protein E-cadherin is required for contact-induced
      polarity in many cells. However, it is debated whether E-cadherin functions
      instructively as a spatial cue, or permissively by ensuring adequate adhesion so
      that cells can sense other contact signals. In Caenorhabditis elegans, contacts
      polarize early embryonic cells by recruiting the RhoGAP PAC-1 to the adjacent
      cortex, inducing PAR protein asymmetry. Here we show that the E-cadherin HMR-1,
      which is dispensable for adhesion, functions together with the alpha-catenin HMP
      1, the p120 catenin JAC-1, and the previously uncharacterized linker PICC-1
      (human CCDC85A-C) to bind PAC-1 and recruit it to contacts. Mislocalizing the HMR
      1 intracellular domain to contact-free surfaces draws PAC-1 to these sites and
      depolarizes cells, demonstrating an instructive role for HMR-1 in polarization.
      Our findings identify an E-cadherin-mediated pathway that translates cell
      contacts into cortical polarity by directly recruiting a symmetry-breaking factor
      to the adjacent cortex. 

PMID- 25938817
TI  - The Function of the Distal Interosseous Membrane and its Relevance to the
      Stability of the Distal Radioulnar Joint: An Anatomical and Biomechanical Review.
AB  - The purpose of this article is to review functional anatomy and biomechanics of
      the distal interosseous membrane (DIOM) and its relevance to the stability of the
      distal radioulnar joint. The intact DIOM constrained dorsal dislocation of the
      radius, but it seldom constrained palmar dislocation. A residual ulnar
      translation deformity of the radial shaft in distal radius fractures has the
      potential to cause the distal radioulnar joint instability when the triangular
      fibrocartilage complex injury is also present, because it may result in
      detensioning of DIOM. Ulnar shortening with the osteotomy performed proximal to
      the attachment of the DIOM had a more favorable effect on stability of the DRUJ
      compared with the effect of distal osteotomy, especially in the presence of the
      distal oblique bundle (DOB). The longitudinal resistance to ulnar shortening was
      significantly greater in proximal shortening than in distal shortening. 

PMID- 25938818
TI  - In Situ Electrochemical ELISA for Specific Identification of Captured Cancer
      Cells.
AB  - Circulating tumor cells (CTCs) are cancer cells disseminated from a tumor into
      the bloodstream. Their presence in patient blood samples has been associated with
      metastatic disease. Here, we report a simple system that enables the isolation
      and detection of these rare cancer cells. By developing a sensitive
      electrochemical ELISA method integrated within a microfluidic cell capture
      system, were we able to reliably detect very low levels of cancer cells in whole
      blood. Our results indicate that the new system provides the clinically relevant
      specificity and sensitivity needed for a convenient, point-of-need assay for
      cancer cell counting. 

PMID- 25938819
TI  - Multifunctional Envelope-Type Nano Device: Evolution from Nonselective to Active
      Targeting System.
AB  - A paradigm shift has occurred in the field of drug delivery systems (DDS), one
      being intracellular targeting, and the other, active targeting. An important
      aspect of intracellular targeting involves delivering nucleic acids such as
      siRNA/pDNA rather than small molecular compounds, since the mechanism responsible
      for their entering a target cell is usually via endocytosis, and the efficiency
      of endosomal escape is a critical factor in determining the functional activities
      of siRNA/pDNA. A multifunctional envelope-type nano device (MEND) was developed
      to control the intracellular trafficking of nano carriers containing siRNA/pDNA.
      An octaarginine (R8) modified MEND was developed to achieve this. Considerable
      progress has been made in active targeting to selective tissue vasculature such
      as tumor, adipose tissue, and the lung where endothelial barrier is tight against
      nanoparticles with diameters larger than 50 nm. A dual-ligand system is proposed
      to enhance active targeting ability by virtue of a synergistic interaction
      between a selective ligand and a cell penetrating ligand. Prohibitin targeted
      nanoparticles (PTNP) were developed to target endothelial cells in adipose
      tissue, which deliver apoptotic peptides/proteins to the adipose vasculature.
      Lung endothelial cells can be targeted by means of the GALA peptide, which is
      usually used to enhance endosomal escape. These active targeting systems can
      induce pharmacological effects in in vivo conditions. Finally, a novel strategy
      for producing an original ligand has been developed, especially for the tumor
      vasculature. This progress in DDS promises to extend the area of nanomedicine as
      a breakthrough technology. 

PMID- 25938820
TI  - Source Apportionment of the Anthropogenic Increment to Ozone, Formaldehyde, and
      Nitrogen Dioxide by the Path-Integral Method in a 3D Model.
AB  - The anthropogenic increment of a species is the difference in concentration
      between a base-case simulation with all emissions included and a background
      simulation without the anthropogenic emissions. The Path-Integral Method (PIM) is
      a new technique that can determine the contributions of individual anthropogenic
      sources to this increment. The PIM was applied to a simulation of O3 formation in
      July 2030 in the U.S., using the Comprehensive Air Quality Model with Extensions
      and assuming advanced controls on light-duty vehicles (LDVs) and other sources.
      The PIM determines the source contributions by integrating first-order
      sensitivity coefficients over a range of emissions, a path, from the background
      case to the base case. There are many potential paths, with each representing a
      specific emission-control strategy leading to zero anthropogenic emissions, i.e.,
      controlling all sources together versus controlling some source(s) preferentially
      are different paths. Three paths were considered, and the O3, formaldehyde, and
      NO2 anthropogenic increments were apportioned to five source categories. At rural
      and urban sites in the eastern U.S. and for all three paths, point sources
      typically have the largest contribution to the O3 and NO2 anthropogenic
      increments, and either LDVs or area sources, the smallest. Results for
      formaldehyde are more complex. 

PMID- 25938821
TI  - Dyeing insects for behavioral assays: the mating behavior of anesthetized
      Drosophila.
AB  - Mating experiments using Drosophila have contributed greatly to the understanding
      of sexual selection and behavior. Experiments often require simple, easy and
      cheap methods to distinguish between individuals in a trial. A standard technique
      for this is CO2 anaesthesia and then labelling or wing clipping each fly.
      However, this is invasive and has been shown to affect behavior. Other techniques
      have used coloration to identify flies. This article presents a simple and non
      invasive method for labelling Drosophila that allows them to be individually
      identified within experiments, using food coloring. This method is used in trials
      where two males compete to mate with a female. Dyeing allowed quick and easy
      identification. There was, however, some difference in the strength of the
      coloration across the three species tested. Data is presented showing the dye has
      a lower impact on mating behavior than CO2 in Drosophila melanogaster. The impact
      of CO2 anaesthesia is shown to depend on the species of Drosophila, with D.
      pseudoobscura and D. subobscura showing no impact, whereas D. melanogaster males
      had reduced mating success. The dye method presented is applicable to a wide
      range of experimental designs. 

PMID- 25938823
TI  - High Pressure Homogenization of Porcine Pepsin Protease: Effects on Enzyme
      Activity, Stability, Milk Coagulation Profile and Gel Development.
AB  - This study investigated the effect of high pressure homogenization (HPH) (up to
      190 MPa) on porcine pepsin (proteolytic and milk-clotting activities), and the
      consequences of using the processed enzyme in milk coagulation and gel formation
      (rheological profile, proteolysis, syneresis, and microstructure). Although the
      proteolytic activity (PA) was not altered immediately after the HPH process, it
      reduced during enzyme storage, with a 5% decrease after 60 days of storage for
      samples obtained with the enzyme processed at 50, 100 and 150 MPa. HPH increased
      the milk-clotting activity (MCA) of the enzyme processed at 150 MPa, being 15%
      higher than the MCA of non-processed samples after 60 days of storage. The enzyme
      processed at 150 MPa produced faster aggregation and a more consistent milk gel
      (G' value 92% higher after 90 minutes) when compared with the non-processed
      enzyme. In addition, the gels produced with the enzyme processed at 150 MPa
      showed greater syneresis after 40 minutes of coagulation (forming a more compact
      protein network) and lower porosity (evidenced by confocal microscopy). These
      effects on the milk gel can be associated with the increment in MCA and reduction
      in PA caused by the effects of HPH on pepsin during storage. According to the
      results, HPH stands out as a process capable of changing the proteolytic
      characteristics of porcine pepsin, with improvements on the milk coagulation step
      and gel characteristics. Therefore, the porcine pepsin submitted to HPH process
      can be a suitable alternative for the production of cheese. 

PMID- 25938822
TI  - Gold Nanorod-assisted Optical Stimulation of Neuronal Cells.
AB  - Recent studies have demonstrated that nerves can be stimulated in a variety of
      ways by the transient heating associated with the absorption of infrared light by
      water in neuronal tissue. This technique holds great potential for replacing or
      complementing standard stimulation techniques, due to the potential for increased
      localization of the stimulus and minimization of mechanical contact with the
      tissue. However, optical approaches are limited by the inability of visible light
      to penetrate deep into tissues. Moreover, thermal modelling suggests that
      cumulative heating effects might be potentially hazardous when multiple stimulus
      sites or high laser repetition rates are used. The protocol outlined below
      describes an enhanced approach to the infrared stimulation of neuronal cells. The
      underlying mechanism is based on the transient heating associated with the
      optical absorption of gold nanorods, which can cause triggering of neuronal cell
      differentiation and increased levels of intracellular calcium activity. These
      results demonstrate that nanoparticle absorbers can enhance and/or replace the
      process of infrared neural stimulation based on water absorption, with potential
      for future applications in neural prostheses and cell therapies. 

PMID- 25938824
TI  - Correction: Cancer-Associated Fibroblasts in a Human HEp-2 Established Laryngeal
      Xenografted Tumor Are Not Derived from Cancer Cells through Epithelial
      Mesenchymal Transition, Phenotypically Activated but Karyotypically Normal.

PMID- 25938825
TI  - [Protective effects and possible mechanisms of hepatic fibrosis against APAP
      induced lethal injury].
AB  - OBJECTIVE: To investigate the protective effects of hepatic fibrosis against a
      lethal dose of acetaminophen (APAP) and its underlying mechanisms using a carbon
      tetrachloride (CCl4)-induced mouse model of fibrosis. METHODS: The experimental
      model of hepatic fibrosis was established by intraperitoneal injection of CC14
      (in mineral oil), twice a week for 6 weeks; mice given a 6-week course of mineral
      oil injections served as normal controls. At the end of fibrosis induction, the
      expmimental (Fib group) and control (Norm group) mice were challenged with APAP
      (1 g/kg). Sera and liver tissues were harvested for analyses.To assess tolerance
      of the normal and fibrotic mice to the lethal dose of APAP, the survival
      rate,serum alanine aminotransferase (sALT) levels and hepatic histopathological
      changes were compared before and after the acute APAP challenge.HMGB 1 expression
      was analyzed by immunohistochemistry.One-way ANOVA test and Newman-Keuls test
      were used in statistical analysis. RESULTS: The fibrotic liver was tolerant to
      the lethal dose of APAP,as evidenced by:(1) significantly higher survival rate in
      the Fib +/- APAP group (80% vs. Norm+APAP group: 0%); (2) markedly lower sALT
      levels in the Fib+APAP group (6 437 +/- 1 913 U/L vs. 12 456 +/- 3 441 U/L),
      P=0.022; (3) remarkably well-preserved liver architecture in the Fib+APAP
      group.Immunohistochemical analysis showed high HMGB1 expression and cytoplasmic
      translocation in the Norm+APAP group,which was absent in the Fib+APAP group.
      CONCLUSIONS: CCl4-induced liver fibrosis protects mice against lethal dose of
      APAP, Possibly by a mechanism involving inhibition of the cytoplasmic
      translocation of HMGB1.

PMID- 25938826
TI  - [Role of R-Spondin1 in the activation of hepatic stellate cells].
AB  - OBJECTIVE: To investigate the role of R-Spondinl in the activation of hepatic
      stellate cells (HSCs). METHODS: Twenty-four healthy male Kunming mice were
      randomly divided into the following two groups:fibrosis model group (n=16) and
      control group (n=8). Hepatic fibrosis was induced by subcutaneous injections of
      CC14 (20% in olive oil) at a dose of 5 ml/kg twice per week. After 10 weeks, the
      animals were sacrificed by CO(2) over-exposure and liver tissues were
      harvested.The protein and mRNA levels of R-Spondin1, alphat-SMA,and collagen I
      were examined by Western blot assay and real-time PCR respectively.
      Additionally,HSCs were isolated from the mice liver tissues to examine the time
      series expression changes of R-Spondinl, alpha-SMA, and nuclear beta-catenin.TCF
      activity was analyzed by luciferase reporter assay.Moreover,HSCs were cocultured
      with recombinant R-Spondin1 and DKK1 to evaluate dose-response. RESULTS: R
      Spondinl expression was significantly higher in the fibrosis model group than in
      the control group (protein level:3.16 +/- 0.18 vs. 0.99 +/- 0.16, t =13.31, P <
      0.01; mRNA level:4.36 +/- 0.26 vs. 0.98 +/- 0.12, t =21.46, P < 0.01).The culture
      activated mouse HSCs showed up-regulated TCF activity (5.33 +/- 0.34 vs. non
      activated: 1.03 +/- 0.09, t =20.93, P < 0.01), nuclear beta-catenin expression
      (4.47 +/- 0.21 vs. 0.97 +/- 0.14, t =25.25, P < 0.01), and R-Spondin1 expression
      (protein level: 4.54 +/- 0.18 vs. 1.04 +/- 0.12, t =31.17, P < 0.01; mRNA
      level:5.13 +/- 0.15 vs. 1.01 +/- 0.16, t=38.06, P < 0.01). Exogenous stimulation
      of freshly isolated mouse HSCs with recombinant R-Spondin1 induced a dose
      dependent increase in both TCF activity and the expression of nuclear beta
      catenin and alphat-SMA. DKK1 down-regulated activities of factors in the WNT
      signaling pathway and repressed activation of HSCs. Conclusion R-Spondin1 may
      promote HSC activation by enhancing the canonical WNT signaling pathway.

PMID- 25938827
TI  - [Study of the mechanism underlying the effect of SOCS3 rs4969170 A/G polymorphism
      on the occurrence of insulin resistance in chronic hepatitis C patients].
AB  - OBJECTIVE: To study the mechanism underlying the effect of the SOCS3 rs4969170
      A/G alleles on the occurrence of insulin resistance (IR) in patients with chronic
      hepatitis C. METHODS: The promoter region of the SOCS3 gene was amplified by
      PCR,and luciferase expression vectors were constructed and transfected into
      HepG2,Huh7 cell lines.The relative luciferase activity of each expression vector
      was assessed by the dual luciferase reporter gene assay system.Western blotting
      was used to detect SOCS3 protein expression in PBMCs from groups of patients with
      the rs4969170 AA and AG genotypes.The state of IR in eight patients was evaluated
      by determining their HOMA-IR. RESULTS: The pGL3-A, PGL3-G and pGL3-control
      vectors showed significantly different luciferase expression in the HepG2 cells
      (0.121 00 +/- 0.022 07,0.027 00+/-0.012 49 and 0.043 33 +/- 0.005 51; F =48.068,
      P=0.001) and in the Huh7 cell lines (0.164 70 +/- 0.007 10,0.027 33 +/- 0.017 04
      and 0.033 67 +/- 0.014 98; F =115.137, P=0.001). The expression of SOCS3 protein
      was significantly higher in the rs4969170 AA genotype group than in the AG
      genotype group (1.22 +/- 0.40 vs. 0.30 +/- 0.19; t =4.149, P=0.006).The IR index
      of patients with the rs4969170 AA genotype and the AG genotype was 4.11 +/- 2.62
      and 1.47 +/- 1.01 respectively.There were three patients with IR in the rs4969170
      AA genotype group and one in the rs4969170 AG group. There was no statistically
      significant difference between the two genotype groups (t=1.881, P=0.109).
      CONCLUSIONS: The SOCS3 rs4969170 A haplotype may enhance transcriptional activity
      of the gene promoter to regulate gene expression, thereby increasing
      intracellular SOCS3 protein level and ultimately interfering with insulin
      signaling and causing IR in patients with chronic hepatitis C.

PMID- 25938828
TI  - [Correlation analysis of chronic hepatitis C with nodular goiter].
AB  - OBJECTIVE: To assess the relationship between nodular goiter and hepatitis C
      virus infection. METHODS: Ninety-seven cases of early treatment in patients with
      chronic hepatitis C were collected for analysis.Data on patient age,sex,hepatitis
      duration and other general information were collected.In addition, data on
      clinical measures of thyroid function (including T3, t4, tSH) and thyroid
      autoantibodies (thyroid peroxidase antibody TPO-Ab, thyroglobulin antibody Tg
      Ab), as well as findings from thyroid dimensional ultrasonography were collected.
      One hundred and eleven cases of early treatment in patients with chronic
      hepatitis B and 106 eases of females 40 years old or older with high risk of
      nodular goiter were collected for use as controls.The relationship between
      nodular goiter with thyroid function, thyroid autoantibodies levels,sex,age,and
      hepatitis C virus infection were statistically analyzed. RESULTS: The prevalence
      rates of nodular goiter in the chronic hepatitis C group, the chronic hepatitis B
      group and the more than or equal to 40 year-old women with high risk of nodular
      goiter were 53.6%,36.9% and 59.4% respectively.The prevalence rates of nodular
      goiter in the chronic hepatitis C group and the more than or equal to 40 year-old
      women with high risk of nodular goiter were significantly higber than that in the
      chronic hepatitis B group (x2 values: 5.820 and 10.996, P < 0.05). The average
      age of patients with chronic hepatitis C combined with nodular goiter was
      significantly higher than their counterparts without goiter (F=6.408, P <
      0.05),and the prevalence rate in the more than or equal to 40 year-old women with
      high risk of nodular goiter was significantly higher than that of their
      counterparts who were less than 40 years-old (60.0% vs. 23.5%; x2 =7.499, P less
      than 0.05). The prevalence of nodular goiter in patients with chronic hepatitis C
      was significantly greater for females than for males (62.1% vs. 41.0%; x 2
      =4.152, P < 0.05).The prevalence of nodular goiter in patients with chronic
      hepatitis C was also significantly higher for females more than or equal to 40
      years old than for males (70.2%, 33/47 vs. 45.5%,15/33; x2 = 4.952, P < 0.05).The
      duration of hepatitis, thyroid function and thyroid autoantibodies were similar
      between the patients in the chronic hepatitis C group with or without nodular
      goiter. CONCLUSIONS: The patients with chronic hepatitis C had a higher
      prevalence of nodular goiter,with an average of up to 53.6%, than the patients
      with chronic hepatitis B,and the women the more than or equal to 40 years old had
      even higher prevalence, at 70.2%, suggesting that patients with chronic hepatitis
      C should be routinely examined by thyroid ultrasound. Thyroid function and
      thyroid autoantibodies were not correlated with prevalence of goiter among the
      chronic hepatitis C patients.

PMID- 25938829
TI  - [Predictive value of telbivudine in preventing mother-to-infant transmission of
      hepatitis B virus in pregnant women with high viremia].
AB  - OBJECTIVE: To investigate the efficacy and safety of telbivudine for blocking
      mother-to-child transmission of hepatitis B virus (HBV) in pregnant women with
      high viremia. METHODS: A total of 128 pregnant women with high HBV load (HBV DNA
      >= 1.0*107 copies/ml and positive for hepatitis B surface antigen (HBsAg)) were
      enrolled in the study from January 2009 to January 2013 and divided into the
      following three groups:group A (n=42) treated with telbivudine at 12 weeks of
      gestation until postpartum 12 weeks; group B (n=41) treated with telbivudine at
      20 to 28 weeks of gestation until postpartum 12 weeks; group C (n=45; control
      group) with no telbivudine treatment.All study participants were given compound
      giyeyrrhizin for liver protection. All infants born to the women from the three
      groups were vaccinated with hepatitis B immunoglobulin (200 IU) and the HBV
      vaccine (20 tg) ager birth. The mother-to-infant transmission of HBV was
      indicated by the presence of HBsAg in infants at 7 months after birth.The
      maternal HBV DNA levels of the women in the three groups were statistically
      compared with the HBsAg positive rates in their neonates. RESULTS: There were no
      significant differences in the HBV DNA levels between the three groups before
      treatment (P more than 0.05). The pre-delivery level of HBV DNA in group A (0.553
      +/- 1.588 log10 copies/ml) and in group B (0.486 +/- 1.429 log10 copies/ml) was
      significantly decreased compared to that in group C (7.698 +/- 0.255 log10
      copies/ml) (both P < 0.01).The post-delivery (12 weeks) level of HBV DNA in group
      A (0.381 +/- 1.116 log10 copies/ml) and in group B (0.335 +/- 1.073 log10
      copies/ml) was significantly decreased compared to that in group C (7.728 +/-
      0.277 log10 copies/ml) (both P < 0.01).There were no significant differences in
      the HBV DNA levels between group A and group B (P > 0.05). No infants in group A
      or group B were HBsAg-positive,while the HBsAg-positive rote was 17.4% in group C
      (P=0.012; P=0.015). CONCLUSIONS: Telbivudine treatment starting from the 12th
      week of gestation or from the 20-28th week of gestation can significantly
      decrease the serum HBV DNA level in peripheral blood of pregnant women with high
      viremia and reduce the infection rate of HBV in their neonates.

PMID- 25938830
TI  - [Clinical control of different sequential order of three-dimensional conformal
      radiotherapy combined with transcatheter arterial chemoembolization for portal
      vein tumor thrombus in patients with hepatocellular carcinoma].
AB  - OBJECTIVE: To study the influence of the sequence of three-dimensional conformal
      radiotherapy (3DCRT) and transcatheter arterial chemoembolization (TACE) on the
      efficacy and toxicity of treatment in patients with hepatocellular carcinoma
      (HCC) with portal vein tumor thrombus (PVTT). METHODS: A total of 65 patients who
      were diagnosed with primary HCC with PVTT were enrolled in the study from
      November 2008 to March 2012 and were randomly divided into the following two
      groups:group A,32 patients treated with 3DCRT followed by TACE; group B,33
      patients treated with TACE followed by 3DCRT. RESULTS: The total efficacy rates
      of groups A and B were 68.8% and 69.7% (x2 =0.232, P < 0.793). The survival
      rates,effective percentage of PVTT and AFP remission rates were not significantly
      different between group A and group B.The exacerbation rate of liver function was
      significantly higher for group B than for group A (P < 0.05). No serious
      complication was found in the follow-up period for either group. CONCLUSION: The
      combination of 3DCRT and TACE is a relatively effective local treatment for
      patients with primary HCC and PVTT.Compared with TACE followed by 3DCRT, 3DCRT
      followed by TACE may have a negative influence on liver function.

PMID- 25938831
TI  - [Diagnostic value of serum Golgi protein-73 (GP73) combined with AFP-L3% in
      hepatocellular carcinoma: a meta-analysis].
AB  - OBJECTIVE: To investigate the diagnostic value of serum Golgi protein-73 (GP73)
      combined with the AFP-L3% test for hepatocellular carcinoma. METHODS:
      Comprehensive electronic and manual searches were performed to retrieve relevant
      studies on GP73 combined with AFP-L3% for diagnosis of hepatocellular carcinoma.
      After screening of the studies according to inclusion criteria and extraction of
      the data,meta-analysis was performed in Meta-disc 1.4 and Stata 12.0. RESULTS:
      Eleven studies that met the inclusion criteria were selected from the total 138
      references with potential relevance.The threshold effect was not found in the
      GP73 combined with AFP-L3% for the diagnosis of liver
      cancer.However,heterogeneity was found in this meta-analysis. The pooled
      sensitivity and specificity of GP73 combined with AFP-L3% was 0.853 and 0.960
      respectively. The area under summary receiver operating characteristics curve was
      0.948, and the Q index was 0.888. CONCLUSION: GP73 combined with AFP-L3% can
      significantly improve the diagnostic sensitivity and specificity to a high level,
      and can improve the diagnosis rate of hepatocellular carcinoma.

PMID- 25938832
TI  - [Role of PI3K/Akt pathway in endoplasmic reticulum stress and apoptosis induced
      by saturated fatty acid in human steatotic hepatocytes].
AB  - OBJECTIVE: To investigate the roles of PI3K/Akt signaling in the unfolded protein
      response (UPR) and non-UPR signaling pathways of endoplasmic reticulum stress and
      apoptosis in hepatocytes under conditions of saturated fatty acid-induced
      steatosis. METHODS: A steatosis model of hepatocytes (L02 cell and HepG2 cell
      line) was induced by palmitate sodium saturated fatty acids.The hepatocytes were
      divided into normal control group,experimental group (treated with palmitate
      sodium) and intervention group (treated with palmitate sodium and LY294002, a
      PI3K/Akt inhibitor). Cell apoptosis was detected by flow cytometry with Annexin
      V/PI double-staining.Western blot analysis was used to examine the protein
      expression of GRP78, PI3K, P-PI3K,Akt, P-Akt, CHOP and Bax.The F test and t-test
      were used in statistical analyses. RESULTS: Flow cytometry showed that palmitate
      sodium induced cell apoptosis in steatotic hepatocytes;moreover, a significant
      increase in cell apoptosis was observed in the palmitate sodium-induced steatotic
      hepatocytes in the presence of LY294002.For the normal control group, the
      experimental group and the intervention group, the apoptosis ratios of L02 cells
      were 4.41 +/- 0.78% vs. 6.01 +/- 1.49% vs. 19.50 +/- 2.53% after 24 hours of
      treatment,and 12.56 +/- 2.78% vs. 29.72 +/- 6.39% vs. 44.60 +/- 4.17% after 48
      hours of treatment in respectively (all P < 0.05),and of HepG2 cells were 11.16
      +/- 1.15% vs. 17.50 +/- 6.83% vs. 30.41 +/- 3.62% after 24 hours of treatment,
      and 22.37 +/- 1.24% vs. 33.85 +/- 5.79% vs. 48.56 +/- 4.21% after 48 hours of
      treatment (all P < 0.05). Western blot analysis showed that expression of GRP78
      was significantly upregulated in the palmitate sodium-induced steatosis
      hepatocytes, indicating activation of endoplasmic reticulum stress. In addition,
      the palmitate sodium treatment also activated the PI3K/Akt pathway,induced
      expression of CHOP and Bax of the UPR and non-UPR signaling pathways
      respectively. Moreover, Pretreatment with LY294002 inhibited the palmitate sodium
      induced-phosphorylation of PI3K and Akt, and promoted upregulation of CHOP and
      Bax induced by palmitate sodium. CONCLUSION: The PI3K/Akt pathway may be involved
      in regulation of the UPR and non-UPR signaling pathways of endoplasmic reticulum
      stress and may promote apoptosis of hepatocytes by enhancing the expression of
      CHOP and Bax protein in saturated fatty acid-induced steatotic hepatocytes.

PMID- 25938833
TI  - [Role of PI3K/AKT pathways in mitomycin-mediated apoptosis of WB-F344 cells].
AB  - OBJECTIVE: To investigate the role of p38MAPK and PI3K/AKT pathways in mitomycin
      (MMC)-induced apoptosis in the liver stem-like cell line WB-F344. METHODS: WB
      F344 cells were exposed to MMC and apoptosis was evaluated by flow cytometry and
      DNA fragmentation. Phospho-MAPK and phospho-PI3K/AKT were detected by western
      blotting. RESULTS: MMC induced apoptosis in WB-F344 cells at 6h after addition of
      MMC; the maximum level of apoptosis was reached at 24h after MMC exposure. The
      apoptosis effects of MMC were concentration dependent and inhibited when the PI3K
      pathway was abolished by the specific inhibitor LY294002, but not inhibited when
      the p38MAPK pathway was abolished by inhibitor SB203508. CONCLUSION: Apoptosis of
      WB-F344 cells can be induced by MMC.Although MMC can activate both the PI3K/AKT
      and p38MAPK pathways, the apoptosis effect of MMC occurs via a PI3K pathway and
      is not dependent on the p38MAPK pathway.

PMID- 25938835
TI  - [MRV comparison of the angle between the right hepatic vein and the inferior vena
      cava for patients with membranous obstruction of the inferior vena cava].
AB  - OBJECTIVE: To determine whether there are differences in both the right hepatic
      vein (RHV) morphology and the size of the angle between the inferior vena cava
      and the RHV in patients with membranous obstruction of the inferior vena cava
      (MOVC),in healthy individuals and in patients with cinhosis (HLC), in order to
      help guide development of an effective interventional treatment program. METHODS:
      Consecutive patients (n=248) were divided into the following three groups: group
      A (control; n=94), group B (MOVC patients; n=68), group C (HLC patients; n=86).
      The angle between the hepatic vein and inferior vena cava was measured and
      defined as the T value. The morphology of the RHV was classified as N, U, or I.
      The difference of the constituent ratio was compared among the three groups for
      the T value and the angle type.Measurement data was calculated as x +/- s,and
      groups were compared using one-way ANOVA; count data was calculated as relative
      number, and groups were compared using the chi-square test. RESULTS: The average
      T value of group B was significantly higher than that of group A (56.1 +/- 13.7
      vs. 49.3 +/- 7.8, P=0.010) and of group C (vs. 51.5 +/- 10.0, P < 0.001); the
      difference was statistically significant (F=8.750, P < 0.001), but there was no
      significant difference between the groups A and C.N-type proportion of B group
      was 48.5% (33/68), greater than that of group A(16.0%,15/94) and C (16.3%,
      14/86), x2 = 20.1, x2 =18.6.U-type proportion of B group was 11.8% (8/68),
      smaller than that of groups A (28.7%,27/94) and C (37.2%, 32/86), 2 2 = 6.70, x2
      =12.8, and the differences were statistically significant (P < 0.01). For groups
      A and C, the N and U types were not significantly different. CONCLUSION: The
      angle between the RHV and the inferior vena cava in MOVC patients is
      morphologically different from that in healthy humans, with the angle value in
      MOVC patients being slightly larger. However, this difference is irrelevant to
      cirrhosis.

PMID- 25938834
TI  - [Magnesium isoglycyrrhizinate prevention of chemotherapy-induced liver damage
      during initial treatment of patients with gastrointestinal tumors].
AB  - OBJECTIVE: To investigate the preventive effect of magnesium isoglycyrrhizinate
      against acute drug-induced liver damage from initial chemotherapy treatment in
      patients with gastrointestinal cancer. METHODS: A total of 216 cases with early
      stage gastric cancer and indications for systemic chemotherapy that had been
      diagnosed with gastrointestinal malignant tumors by pathology in our hospital
      were enrolled for study during the period of January 2011 to June 2013.Using a
      prospective randomized controlled study design,differences were assessed between
      groups treated with glycyrrhizic acid magnesium (experimental group; n=114) or
      glutathione (control group; n=102) and the FOLFOX regimen (n=104) or the XELOX
      regimen (n=112).Patients in the FOLFOX group received intravenous infusion of L
      OHP (85 mg/m2) at day 1,followed by a bolus injection of 5-FU (400 mg/m2) at days
      1-2 and continuous intravenous infusion of 5-FU (600 mg/m2) for 22 h at days 1
      2,with one cycle comprising 2 weeks. Patients in the XELOX group received
      intravenous infusion of L-OHP (130 mg/m2) at day 1, followed by capecitabine (1
      000 mg/m2) oral twice a day at days 1-14,with one cycle comprising 3 weeks.In the
      first cycle of chemotherapy,serum was extracted from the patients at 1 day before
      chemotherapy and 1 week after chemotherapy.An automated biochemistry analyzer was
      used to measure alanine aminotransferase (ALT), aspartate aminotransferase (AST),
      total bilirubin (TBil) and alkaline phosphatase (ALP). Differences between groups
      were statistically analyzed by the t-test and x2 test. RESULTS: Among the total
      216 cases treated with chemotherapy,40 showed hepatic biochemical abnormalities
      (12 cases in the experimental group, 28 cases in the control group), and the
      effect of prevention was significantly different between the two groups (10.53%
      vs. 27.25%; x2 =10.219, P less than 0.005).The acute and subacute hepatic
      toxicity reaction degrees for the experimental and the control groups were:
      0:94.78% vs. 88.2%; 1:5.3% vs. 11.8% (x2 =6.99, P < 0.01). One week after
      chemotherapy, the liver biochemical indexes in the experimental group (ALT:35.93
      +/- 8.33 U/L; AST:24.84 +/-2.91 U/L; TBil:13.29 +/- 5.89 mumol/L; ALP:125.1 +/-
      53.61 U/L) were statically different from those in the control group (all P <
      0.05). The liver biochemical indexes before and after chemotherapy were also
      significantly different between the experimental group (ALT:13.18t3.23 U/L;
      AST:5.39 +/- 2.57 U/L; TBil:2.79 +/- 0.23 mumol/L; ALP:52.08 +/- 4.83 U/L) and
      the control group (all P < 0.05).One week after chemotherapy in the experimental
      group, the groups treated with the FOLFOX regimen or the XELOX regimen showed no
      statistical differences in the liver biochemical indexes.One week after
      chemotherapy in the control group, though, the groups treated with the FOLFOX
      regimen showed significantly lower AST (26.24 +/- 3.50 U/L vs. 29.80 +/- 6.57
      U/L, t=-2.431, P < 0.05),but the residual liver biochemical indexes were not
      significantly different.In the experimental group, the FOLFOX group showed
      significantly lower ALP (53.44 +/- 2.47 U/L vs. 56.58 +/- 6.70 U/L, t =-2.201, P
      < 0.05), AST (6.48 +/- 3.15U/L vs. 9.88 +/- 4.57 U/L, t =-5.223, P < 0.05), but
      the residual liver biochemical index was not significantly different. CONCLUSION:
      Magnesium isoglycyrrhizinate is an effective drug for the prevention of drug
      induced liver damage after initial chemotherapy in patients with early stage
      gastrointestinal cancer.

PMID- 25938836
TI  - Identification and Molecular Characterization of Two Acetylcholinesterases from
      the Salmon Louse, Lepeophtheirus salmonis.
AB  - Acetylcholinesterase (AChE) is an important enzyme in cholinergic synapses. Most
      arthropods have two genes (ace1 and ace2), but only one encodes the predominant
      synaptic AChE, the main target for organophosphates. Resistance towards
      organophosphates is widespread in the marine arthropod Lepeophtheirus salmonis.
      To understand this trait, it is essential to characterize the gene(s) coding for
      AChE(s). The full length cDNA sequences encoding two AChEs in L. salmonis were
      molecularly characterized in this study. The two ace genes were highly similar
      (83.5% similarity at protein level). Alignment to the L. salmonis genome revealed
      that both genes were located close to each other (separated by just 26.4 kbp on
      the L. salmonis genome), resulting from a recent gene duplication. Both proteins
      had all the typical features of functional AChE and clustered together with AChE
      type 1 proteins in other species, an observation that has not been described in
      other arthropods. We therefore concluded the presence of two versions of ace1
      gene in L. salmonis, named ace1a and ace1b. Ace1a was predominantly expressed in
      different developmental stages compared to ace1b and was possibly active in the
      cephalothorax, indicating that ace1a is more likely to play the major role in
      cholinergic synaptic transmission. The study is essential to understand the role
      of AChEs in resistance against organophosphates in L. salmonis. 

PMID- 25938837
TI  - Variants in Nebulin (NEB) Are Linked to the Development of Familial Primary Angle
      Closure Glaucoma in Basset Hounds.
AB  - Several dog breeds are susceptible to developing primary angle closure glaucoma
      (PACG), which suggests a genetic basis for the disease. We have identified a four
      generation Basset Hound pedigree with characteristic autosomal recessive PACG
      that closely recapitulates PACG in humans. Our aim is to utilize gene mapping and
      whole exome sequencing approaches to identify PACG-causing sequence variants in
      the Basset. Extensive clinical phenotyping of all pedigree members was conducted.
      SNP-chip genotyping was carried out in 9 affected and 15 unaffected pedigree
      members. Two-point and multipoint linkage analyses of genome-wide SNP data were
      performed using Superlink-Online SNP-1.1 and a locus was mapped to chromosome 19q
      with a maximum LOD score of 3.24. The locus contains 12 Ensemble predicted canine
      genes and is syntenic to a region on chromosome 2 in the human genome. Using
      exome-sequencing analysis, a possibly damaging, non-synonymous variant in the
      gene Nebulin (NEB) was found to segregate with PACG which alters a
      phylogenetically conserved Lysine residue. The association of this variants with
      PACG was confirmed in a secondary cohort of unrelated Basset Hounds (p = 3.4 * 10
      4, OR = 15.3 for homozygosity). Nebulin, a protein that promotes the contractile
      function of sarcomeres, was found to be prominently expressed in the ciliary
      muscles of the anterior segment. Our findings may provide insight into the
      molecular mechanisms that underlie PACG. The phenotypic similarities of disease
      presentation in dogs and humans may enable the translation of findings made in
      this study to patients with PACG. 

PMID- 25938838
TI  - Protective Effects of Valproic Acid, a Histone Deacetylase Inhibitor, against
      Hyperoxic Lung Injury in a Neonatal Rat Model.
AB  - OBJECTIVE: Histone acetylation and deacetylation may play a role in the
      pathogenesis of inflammatory lung diseases. We evaluated the preventive effect of
      valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, on neonatal
      hyperoxic lung injury. METHODS: Forty newborn rat pups were randomized in
      normoxia, normoxia+VPA, hyperoxia and hyperoxia+VPA groups. Pups in the normoxia
      and normoxia+VPA groups were kept in room air and received daily saline and VPA
      (30 mg/kg) injections, respectively, while those in hyperoxia and hyperoxia+VPA
      groups were exposed to 95% O2 and received daily saline and VPA (30 mg/kg)
      injections for 10 days, respectively. Growth, histopathological, biochemical and
      molecular biological indicators of lung injury, apoptosis, inflammation, fibrosis
      and histone acetylation were evaluated. RESULTS: VPA treatment during hyperoxia
      significantly improved weight gain, histopathologic grade, radial alveolar count
      and lamellar body membrane protein expression, while it decreased number of
      TUNEL(+) cells and active Caspase-3 expression. Expressions of TGFbeta3 and
      phospho-SMAD2 proteins and levels of tissue proinflammatory cytokines as well as
      lipid peroxidation biomarkers were reduced, while anti-oxidative enzyme
      activities were enhanced by VPA treatment. VPA administration also reduced HDAC
      activity while increasing acetylated H3 and H4 protein expressions. CONCLUSIONS:
      The present study shows for the first time that VPA treatment ameliorates lung
      damage in a neonatal rat model of hyperoxic lung injury. The preventive effect of
      VPA involves HDAC inhibition.

PMID- 25938839
TI  - Glycated Hemoglobin, Fasting, Two-hour Post-challenge and Postprandial Glycemia
      in the Diagnosis and Treatment of Diabetes Mellitus: Are We Giving Them the Right
      Interpretation and Use?
AB  - This brief review is aimed to point out the importance of considering glycated
      hemoglobin, fasting blood glucose, post-glucose-load glycemia, and postprandial
      glycemia into an evolutive and dynamic criteria that may grant a better concept
      and understanding of the diagnostic and therapeutic status of individual patients
      with type-2 diabetes mellitus. 

PMID- 25938840
TI  - Satisfaction with Healthcare Services and Adherence to Antiretroviral Therapy
      among Patients with HIV Attending Two Public Institutions.
AB  - BACKGROUND: Discontinuation of antiretroviral therapy has adverse consequences in
      HIV patients and is a major public health problem. We analyzed the relationship
      between satisfaction with healthcare services and adherence to antiretroviral
      therapy among patients with HIV in Mexico City. MATERIAL AND METHODS: We
      conducted a cross-sectional study with patients with HIV (n = 557) who were
      treated in two public institutions. An ad hoc questionnaire was used to assess
      perceived satisfaction with healthcare services (i.e. physician/patient
      relationship, performance of services, and administrative aspects with focus on
      specific areas) and adherence to HIV treatment (i.e. failure to take
      antiretroviral therapy on previous day, week, and month). RESULTS: The higher
      prevalence of non-adherence to antiretroviral therapy was during the previous
      month (23.5%). Dissatisfied patients with the relationship with their physician
      were more likely to have low adherence during the previous month (OR: 1.90; p <
      0.05). Those who were dissatisfied with the care provided in specific clinical
      areas had low adherence (OR: 1.67; p = 0.051), but the difference disappeared
      (OR: 1.26; p = 0.443) after adjusting for satisfaction with physician/patient
      relationship. CONCLUSIONS: The quality of the relationship between physician and
      patients is an aspect that impacts on adherence to antiretroviral therapy. It is
      necessary to promote effective communication between health personnel and
      patients with HIV.

PMID- 25938841
TI  - Changes in frequency of delayed graft function in deceased donor renal transplant
      recipient in a tertiary care center in Mexico.
AB  - BACKGROUND: Delayed graft function (DGF) is defined as the need for dialysis
      within the first seven days of transplantation. The frequency of DGF has
      decreased in the last five years compared with the previous 20 years of the
      kidney transplant program at a Mexican referral hospital. OBJECTIVE: To determine
      the incidence and risk factors for DGF in the past five years (2009-2013).
      METHODS: We analyzed a retrospective cohort of renal transplant recipients from
      deceased donors at our hospital between March 2009 and May 2013 (Period 2), and
      compared the results with a previously evaluated cohort (Period 1, between
      January 1990 and February 2009). RESULTS: During the analyzed period, 78 deceased
      donor transplants were performed. The frequency of DGF was 9%. Multivariate
      analysis showed that recipient older age (OR: 1.074419; 95% CI: 1.0009-1.155116;
      p = 0.05), transoperative amines administration (OR: 7.73; 95% CI: 1.037-57.6; p
      = 0.046), and hypotension during surgery in the recipient (OR: 11.6; 95% CI: 1.33
      100.8; p = 0.026) were risk factors for DGF. CONCLUSION: The incidence of DGF has
      significantly decreased in the past five years when compared to the previous 20
      years in our hospital.

PMID- 25938842
TI  - Percutaneous Vertebroplasty Versus Conservative Treatment and Rehabilitation in
      Women with Vertebral Fractures due to Osteoporosis: A Prospective Comparative
      Study.
AB  - BACKGROUND: Percutaneous vertebroplasty is commonly used in the management of
      osteoporosis-related vertebral fractures, although there is controversy on its
      superiority over conservative treatment. Here we compare pain and function in
      women with vertebral osteoporotic fractures who underwent percutaneous
      vertebroplasty versus conservative treatment with a protocolized rehabilitation
      program. METHODS: A longitudinal and comparative prospective study was conducted.
      Women >= 60 years of age with a diagnosis of osteoporosis who had at least one
      vertebral thoracic or lumbar compression fracture were included and divided into
      two groups, conservative treatment or vertebroplasty. The Visual Analogue Scale
      (VAS) and Oswestry Disability Index (ODI) were used to assess pain and function,
      respectively, as the outcome measures. RESULTS: We included 31 patients, 13 (42%)
      treated with percutaneous vertebroplasty and 18 (58%) with conservative
      treatment. Baseline clinical characteristics, bone densitometry and fracture data
      were similar in both groups. At baseline, VAS was 73.1 +/- 28.36 in the
      vertebroplasty group and 68.6 +/- 36.1 mm in the conservative treatment group (p
      = 0.632); at three months it was 33.11 +/- 10.1 vs. 42 +/- 22.21 mm (p = 0.111);
      and at 12 months, 32.3 +/- 11.21 vs. 36.1 +/- 12.36 mm (p = 0.821). The ODI at
      baseline was 83% in the vertebroplasty group vs. 85% for conservative management
      (p = 0.34); at three months, 36 vs. 39% (p = 0.36); and at 12 months, 29.38 vs.
      28.33% (p = 0.66). CONCLUSIONS: Treatment with percutaneous vertebroplasty had no
      advantages over conservative treatment for pain and function in this group of
      women >= 60 years of age with osteoporosis.

PMID- 25938843
TI  - Hepatitis C screening in the general population.
AB  - BACKGROUND: A significant number of patients infected with hepatitis C virus
      remain unaware of their infection, as this is a silent disease for many years.
      Patients are frequently detected at advance stages of the disease. OBJECTIVE: To
      identify the prevalence and viremic stage of hepatitis C among a general
      population cohort. METHODS: Anti-hepatitis C virus detection and viral RNA were
      offered without cost to individuals who voluntarily considered it relevant to be
      examined, as part of the World Hepatitis Day annually from 2007-2014. RESULTS: A
      total of 32,945 individuals were analyzed; 57% were female and 43% male. Of them,
      75.7% were between 21-50 years old. In 59%, the sample was obtained at their work
      place and in 41% at the facilities of 12 private laboratories. Anti-hepatitis C
      virus was positive in 194 patients (0.58%), of which 129 (66%) were confirmed
      positive by polymerase chain reaction. The overall prevalence of viremic cases in
      the sample was 0.39%. CONCLUSIONS: Adequate estimation of the prevalence of anti
      hepatitis C virus and viremic population, not only among high-risk groups but
      also in the general population, is central to the allocation of resources in an
      effort to reduce the consequences of the disease.

PMID- 25938844
TI  - Health-Related Quality of Life in leukemia Survivors of Allogeneic Hematopoietic
      Stem Cell Transplantation Employing the Mexican Reduced-Intensity Conditioning.
AB  - BACKGROUND: Quality of life (QOL) is an important consideration in the
      counseling, implementation, and post-treatment management of arduous treatments
      for life-threatening conditions such as allogeneic hematopoietic cell
      transplantation (allo-HCT). OBJECTIVE: To analyze the QOL of leukemia patients
      allografted with the Mexican reduced-intensity conditioning regimen in two
      Mexican academic medical centers. MATERIAL AND METHODS: By means of the quality
      metric short form 36 version 2 to measure generic health concepts, relevant QOL
      was analyzed in leukemia patients who underwent allo-HCT using reduced-intensity
      conditioning on an outpatient basis at either the Centro de Hematologia y
      Medicina Interna de Puebla of the Clinica Ruiz or the Hematology Service of the
      Internal Medicine Department of the Hospital "Dr. Jose Eleuterio Gonzalez" of the
      Universidad Autonoma de Nuevo Leon, and who had survived more than 12 months
      after the allograft, who could be approached, who were in a continued complete
      remission (with or without graft-versus-host disease), and who were willing to
      respond to the questionnaire. Thirty-five patients fulfilling these requirements
      were included, and a sex- and age-matched group of 35 reference subjects was also
      studied. RESULTS: Allografted patients were found to have a slightly better
      mental component summary than the reference subjects (53.23 vs. 48.66 points; p =
      0.01), whereas the physical component summary did not show a difference (54.53
      vs. 52.05 points; p = 0.59). Most of the differences between allografted
      individuals and reference subject controls were not significant. CONCLUSIONS:
      Despite several sources of bias, these data suggest that allografted individuals
      employing the Mexican reduced-intensity conditioning regimen enjoy a health
      related QOL life similar to that of reference subjects, adding another advantage
      of this method of conducting stem cell allografts. However, more work needs to be
      done to elucidate the impact of reduced-intensity conditioning on post allo-HCT
      QOL.

PMID- 25938845
TI  - Neutrophil to lymphocyte ratio as predictor of surgical mortality and survival in
      complex surgery of the upper gastrointestinal tract.
AB  - BACKGROUND: Neutrophil-lymphocyte ratio (NLR) has been proposed as a marker of
      inflammatory response and as a prognostic tool in surgical procedures. OBJECTIVE:
      To evaluate the role of high preoperative NLR (> 4.5) as predictor of morbidity
      and mortality in patients with upper gastrointestinal tract resection, and
      survival in cancer patients. METHODS: Retrospective study of patients undergoing
      upper gastrointestinal tract surgery from 2007 to 2012. Variables associated with
      morbidity, mortality, and survival were analyzed. Univariate and multivariate
      analyses were performed. Significance was considered at p < 0.05. RESULTS: 548
      patients were included. The most common surgical procedures were Whipple (44.3%)
      and gastrectomy (30.7%). Surgical morbidity was 40.5% and mortality 6.4%. Factors
      associated with significant surgical complications were: low body mass index,
      AJCC stage >= III and ASA >= III. Factors associated with mortality were older
      patient age, high NLR, AJCC stage >= III, ASA >= III, blood transfusion and
      Charlson > 4. On multivariate analysis, only high NLR and Charlson > 4 remained
      significant. High NLR was significantly associated with reduced survival in
      patients with malignant neoplasms (three-year survival 76.1 vs. 65.7%; p = 0.04).
      CONCLUSION: High preoperative NLR appears to be a biomarker to predict surgical
      mortality and survival in patients undergoing complex surgery of the upper
      gastrointestinal tract.

PMID- 25938846
TI  - Menopausal women have hypofibrinolysis even in subclinical stage of
      atherosclerosis.
AB  - BACKGROUND: PAI-1 is the main inhibitor of fibrinolysis. Increase in PAI-1 levels
      has been associated with the risk of coronary disease; however, there are few
      studies on the relationship between subclinical atherosclerosis and PAI-1 levels.
      OBJECTIVE: The aim of this study was to analyze the relationship between PAI-1
      level and carotid intima-media thickness in premenopausal and postmenopausal
      women without apparent cardiovascular disease. MATERIAL AND METHODS: A cross
      sectional study was conducted in 142 women aged 45 to 60 years with no history of
      cardiovascular disease. Anthropometric and laboratory measurements were
      performed, including PAI-1 levels. All participants underwent a B-Mode ultrasound
      to measure intima-media thickness. Subclinical atherosclerosis was considered
      when intima-media thickness was >= 0.7 mm and/or an atheromatous plaque was
      observed. RESULTS: Postmenopausal women had greater intima-media thickness than
      premenopausal women (0.688 +/- 0.129 vs. 0.621 +/- 0.113 mm; p < 0.05). Compared
      to women with normal intima-media thickness, women with subclinical
      atherosclerosis had higher PAI-1 levels (23.2 +/- 13.7 vs. 30.4 +/- 20.7 ng/ml; p
      < 0.05). In all participants, intima-media thickness correlated with PAI-1 (r =
      0.302; p = 0.01) and with age (r = 0.358; p = 0001). CONCLUSIONS: An increase in
      intima-media thickness was observed in postmenopausal women compared with
      premenopausal women. Asymptomatic women with increased intima-media thickness had
      higher PAI-1 levels. These findings suggest that fibrinolytic activity is low in
      the subclinical stage of atherosclerosis.

PMID- 25938847
TI  - Pulse oximetry as a screening test for critical congenital heart disease in term
      newborns.
AB  - BACKGROUND: Pulse oximetry has been suggested as a screening test for congenital
      heart disease (CHD) in asymptomatic newborns. However, most newborns in Mexico
      are discharged from the hospital without this evaluation. OBJECTIVE: To evaluate
      pulse oximetry as a screening test for critical congenital heart disease (CCHD)
      in term newborns. METHODS: We conducted a cross-sectional study in term newborns
      between July 2010 and April 2011. Pulse oximetry was determined before hospital
      discharge; in case of post-ductal oxygen saturation < 95%, a Doppler
      echocardiogram was performed. RESULTS: From 1,037 newborns screened, two had
      CCHD, one had pulmonary atresia and ventricular septal defect, and one Ebstein's
      anomaly. Minor CHD was present in 10 babies. The overall prevalence of CHD was
      11.5 per 1000 live births, and the prevalence of CCHD was 3.9 per 1000 live
      births. For those with critical disease, pulse oximetry had a sensitivity of
      100%, specificity 98.8%, positive predictive value 14.2%, negative predictive
      value 100%, and positive likelihood ratio of 86.2. In regression analysis, oxygen
      saturation, respiratory frequency, and postnatal age were related with CCHD.
      CONCLUSIONS: Pulse oximetry had a good sensitivity and specificity for the
      identification of critical congenital heart disease in term newborns. Low oxygen
      saturation, higher respiratory frequency, and early postnatal age were related
      with congenital heart disease.

PMID- 25938848
TI  - Biphasic Sarcomatoid Porocarcinoma.
AB  - Sarcomatoid carcinomas are rare malignant tumors, which usually demonstrate a
      well-differentiated epithelial component in association with a poorly
      differentiated spindle-cell component. Several different subtypes have been
      reported and categorized primarily under the differentiated epithelial component,
      with the majority of cutaneous sarcomatoid carcinomas arising in the setting of a
      basal cell or squamous cell carcinoma. To date, only 4 cases of sarcomatoid
      porocarcinoma have been reported in the literature. The authors present a case of
      an 84-year-old woman with an ulcerated papule on her scalp for several months.
      Histopathology revealed an exophytic and endophytic epidermal proliferation with
      multiple mitoses and ductal differentiation overlying a poorly differentiated,
      infiltrative spindle-cell proliferation in the dermis. Ductal and cystic
      structures were scattered throughout the malignancy. Immunohistochemistry was
      notable for strong and diffuse pancytokeratin positivity, p63 positivity, focally
      positive carcinoembryonic antigen within the ductal lumina, and periodic acid
      schiff-positive, diastase-resistant intracellular deposits. They present the
      findings of this rare case of primary cutaneous sarcomatoid porocarcinoma. 

PMID- 25938849
TI  - Accelerator Mass Spectrometry of Actinides in Ground- and Seawater: An Innovative
      Method Allowing for the Simultaneous Analysis of U, Np, Pu, Am, and Cm Isotopes
      below ppq Levels.
AB  - (236)U, (237)Np, and Pu isotopes and (243)Am were determined in ground- and
      seawater samples at levels below ppq (fg/g) with a maximum sample size of 250 g.
      Such high sensitivity was possible by using accelerator mass spectrometry (AMS)
      at the Vienna Environmental Research Accelerator (VERA) with extreme selectivity
      and recently improved efficiency and a significantly simplified separation
      chemistry. The use of nonisotopic tracers was investigated in order to allow for
      the determination of (237)Np and (243)Am, for which isotopic tracers either are
      rarely available or suffer from various isobaric mass interferences. In the
      present study, actinides were concentrated from the sample matrix via iron
      hydroxide coprecipitation and measured sequentially without previous chemical
      separation from each other. The analytical method was validated by the analysis
      of the Reference Material IAEA 443 and was applied to groundwater samples from
      the Colloid Formation and Migration (CFM) project at the deep underground rock
      laboratory of the Grimsel Test Site (GTS) and to natural water samples affected
      solely by global fallout. While the precision of the presented analytical method
      is somewhat limited by the use of nonisotopic spikes, the sensitivity allows for
      the determination of ~10(5) atoms in a sample. This provides, e.g., the
      capability to study the long-term release and retention of actinide tracers in
      field experiments as well as the transport of actinides in a variety of
      environmental systems by tracing contamination from global fallout. 

PMID- 25938850
TI  - Characterization and cytotoxicity studies of DPPC:M(2+) novel delivery system for
      cisplatin thermosensitivity liposome with improving loading efficiency.
AB  - A novel, metal ion-assisted drug-loading model, in which the metal ion was used
      to modify the microstructure of DPPC bilayers, has been developed to improve the
      drug-loading efficiency of cisplatin thermosensitivity liposomes. The reactions
      of dipalmitoyl phosphatidylcholine (DPPC) with diverse metal ions (Zn(2+),
      Cu(2+), Mn(2+) and Mg(2+)) yield four typical liposomes, which have been
      characterized by FT-IR, Raman and fluorescence techniques; the mechanism for
      higher drug encapsulation efficiency has also been investigated. In these
      prepared liposomes, the conformation of DPPC is changed due to the electrostatic
      interaction between the metal ions and phospholipid acyl group, leading to a
      closer arrangement of the lipid hydrocarbon chains and higher Tm of DPPC. As a
      result, the encapsulation efficiency of metal ion-assisted loading liposome is
      significantly higher than that of metal ion-free state. While for the release
      time, all four metal ion-assisted liposomes could be released within 10min at
      42+/-0.5 degrees C, which approach to the phase transition temperature,
      indicating that the introduction of metal ions into the DPPC bilayer membranes
      has no influence on the thermosensitivity of the liposome. Furthermore, the
      higher cytotoxicity of metal ion-bounded liposomes than that of free cisplatin
      solution suggests that high encapsulation efficiency can cause cytotoxicity
      increase. Hence, this work highlighted that metal ion-assisted loading model
      increased the encapsulation efficiency and cell cytotoxicity of cisplatin in
      thermosensitive liposomes with no obvious effects on sustained and temperature
      dependent drug release. 

PMID- 25938851
TI  - Effect of fatty acids on self-assembly of soybean lecithin systems.
AB  - With the increasing interest in natural formulations for drug administration and
      functional foods, it is desirable a good knowledge of the phase behavior of
      lecithin/fatty acid formulations. Phase structure and properties of ternary
      lecithin/fatty acids/water systems are studied at 37 degrees C, making emphasis
      in regions with relatively low water and fatty acid content. The effect of fatty
      acid saturation degree on the phase microstructure is studied by comparing a
      fully saturated (palmitic acid, C16:0), monounsaturated (oleic acid, C18:1), and
      diunsaturated (linoleic acid, C18:2) fatty acids. Phase determinations are based
      on a combination of polarized light microscopy and small-angle X-ray scattering
      measurements. Interestingly, unsaturated (oleic acid and linoleic acid) fatty
      acid destabilizes the lamellar bilayer. Slight differences are observed between
      the phase diagrams produced by the unsaturated ones: small lamellar, medium cubic
      and large hexagonal regions. A narrow isotropic fluid region also appears on the
      lecithin-fatty acid axis, up to 8wt% water. In contrast, a marked difference in
      phase microsctructure was observed between unsaturated and saturated systems in
      which the cubic and isotropic fluid phases are not formed. These differences are,
      probably, a consequence of the high Krafft point of the C16 saturated chains that
      imply rather rigid chains. However, unsaturated fatty acids result in more
      flexible tails. The frequent presence of, at least, one unsaturated chain in
      phospholipids makes it very likely a better mixing situation than in the case of
      more rigid chains. This swelling potential favors the formation of reverse
      hexagonal, cubic, and micellar phases. Both unsaturated fatty acid systems evolve
      by aging, with a reduction of the extension of reverse hexagonal phase and
      migration of the cubic phase to lower fatty acid and water contents. The kinetic
      stability of the systems seems to be controlled by the unsaturation of fatty
      acids. 

PMID- 25938852
TI  - 1H-Azepine-2-oxo-5-amino-5-carboxylic Acid: A 310 Helix Inducer and an Effective
      Tool for Functionalized Gold Nanoparticles.
AB  - A new alpha,alpha-disubstituted constrained glutamine analogue has been designed
      to decorate gold nanoparticles and to induce a 310-helix when inserted in
      peptides. Using an efficient "one-pot" asymmetric Schmidt reaction between 4
      disubstituted-cyclohexanone and hydroxyalkylazides, 1H-azepine-2-oxo-5-amino-5
      carboxylic acid was prepared. The main (R) isomer was inserted at the N-terminus
      in a very short peptide sequence (i.e., PhCO-(R)-Oxo-Azn-L-Ala-Aib-L-AlaNHMe) and
      a stable 310-helix conformation was obtained, as verified by both NMR experiments
      and molecular dynamics (MD) simulations. Finally, the presence of the hydroxyl
      chain at the nitrogen atom of the ring allowed for the preparation of covered
      chiral gold nanoparticles.

PMID- 25938853
TI  - Early detection of sporadic pancreatic cancer: strategic map for innovation--a
      white paper.
AB  - Innovation leading to significant advances in research and subsequent translation
      to clinical practice is urgently necessary in early detection of sporadic
      pancreatic cancer. Addressing this need, the Early Detection of Sporadic
      Pancreatic Cancer Summit Conference was conducted by Kenner Family Research Fund
      in conjunction with the 2014 American Pancreatic Association and Japan Pancreas
      Society Meeting. International interdisciplinary scientific representatives
      engaged in strategic facilitated conversations based on distinct areas of
      inquiry: Case for Early Detection: Definitions, Detection, Survival, and
      Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies.
      Ideas generated from the summit have led to the development of a Strategic Map
      for Innovation built upon 3 components: formation of an international
      collaborative effort, design of an actionable strategic plan, and implementation
      of operational standards, research priorities, and first-phase initiatives.
      Through invested and committed efforts of leading researchers and institutions,
      philanthropic partners, government agencies, and supportive business entities,
      this endeavor will change the future of the field and consequently the survival
      rate of those diagnosed with pancreatic cancer.

PMID- 25938854
TI  - Pathologic cellular events in smoking-related pancreatitis.
AB  - Pancreatitis, a debilitating inflammatory disorder, results from pancreatic
      injury. Alcohol abuse is the foremost cause, although cigarette smoking has
      recently surfaced as a distinct risk factor. The mechanisms by which cigarette
      smoke and its toxins initiate pathological cellular events leading to
      pancreatitis, have not been clearly defined. Although cigarette smoke is composed
      of more than 4000 compounds, it is mainly nicotine and the tobacco-specific
      nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), which have been
      extensively studied with respect to pancreatic diseases. This review summarizes
      these research findings and highlights cellular pathways which may be of
      relevance in initiation and progression of smoking-related pancreatitis. 

PMID- 25938855
TI  - Effect of mindfulness on vocational rehabilitation outcomes in stable phase
      schizophrenia.
AB  - This report describes the results of a randomized controlled feasibility study of
      the Mindfulness Intervention for Rehabilitation and Recovery in Schizophrenia
      (MIRRORS). MIRRORS is an adaptation of Mindfulness-Based Stress Reduction
      designed to help persons with schizophrenia to persist and perform better at
      work. Thirty-four participants with schizophrenia or schizoaffective disorder who
      were engaged in outpatient services were enrolled in a vocational rehabilitation
      program that included a job placement and then were randomized to receive MIRRORS
      (n = 18) or Intensive Support (n = 16) over a period of 16 weeks. The number of
      hours worked was recorded weekly and job performance was assessed monthly using
      the Work Behavior Inventory. Results of t-tests revealed that participants in the
      MIRRORS group worked a significantly greater number of hours and performed
      significantly better at the end of the 4-month intervention than those in the
      Intensive Support condition. Repeated-measures analysis of variance revealed that
      the MIRRORS group worked more hours each week on average and that this difference
      increased over time as well as having generally better work performance compared
      with the Intensive Support group. Results suggest a link between MIRRORS and
      higher levels of work performance and persistence in people with schizophrenia.
      Further research is indicated to evaluate MIRRORS in a fully powered randomized
      controlled trial.

PMID- 25938856
TI  - Polytrauma transitional rehabilitation programs: Comprehensive rehabilitation for
      community integration after brain injury.
AB  - When the U.S. Congress passed the Veterans Health Programs Improvement Act of
      2004 and the Consolidated Appropriations Act in 2005, Veterans Affairs (VA)
      traumatic brain injury centers responded by establishing and developing the
      polytrauma rehabilitation centers and polytrauma transitional rehabilitation
      programs (PTRPs) across 4 sites in Minneapolis, Minnesota, Palo Alto, California,
      Richmond, Virginia, and Tampa, Florida, in 2007. The 5th PTRP was opened in 2011
      in San Antonio, Texas. This article presents the context of establishing these
      programs within a VA system, describes aspects of programmatic design, and shares
      characteristics and outcomes of individuals served by the first 4 national
      centers. PTRPs provide specialized, interdisciplinary brain injury rehabilitation
      to active-duty service members and veterans with complex rehabilitation needs. A
      total of 286 individuals participated in the first 4 PTRPs during the first 3
      years. Admission and discharge data were collected as part of routine care, and
      data review focused on describing the demographic, injury, and neurobehavioral
      functioning outcomes across 4 sites. Mayo-Portland Adaptability Inventory
      Abilities, Adjustment, and Participation subscales and total scale T-scores
      served as primary functioning outcome measures. Mean scores are presented.
      Statistical analysis found a significant change in total scale T-score from
      admission to discharge, consistent with improved patient functional ability.
      Challenges associated with the development and implementation of programs are
      discussed. Elements of programming may be applicable for other health care
      organizations that seek to improve rehabilitation care delivery.

PMID- 25938857
TI  - "Women's Veteran Identity and Utilization of VA Health Services": Correction to
      Di Leone et al. (2015).
AB  - Reports an error in "Women's Veteran Identity and Utilization of VA Health
      Services" by Brooke A. L. Di Leone, Joyce M. Wang, Nancy Kressin and Dawne Vogt
      (Psychological Services, Advanced Online Publication, Mar 2, 2015, np). In the
      article, the institutional affiliation in the byline of Dawne Vogt did not
      include the National Center for PTSD. All versions of this article have been
      corrected. (

PMID- 25938858
TI  - Electron injection dynamics in high-potential porphyrin photoanodes.
AB  - There is a growing need to utilize carbon neutral energy sources, and it is well
      known that solar energy can easily satisfy all of humanity's requirements. In
      order to make solar energy a viable alternative to fossil fuels, the problem of
      intermittency must be solved. Batteries and supercapacitors are an area of active
      research, but they currently have relatively low energy-to-mass storage capacity.
      An alternative and very promising possibility is to store energy in chemical
      bonds, or make a solar fuel. The process of making solar fuel is not new, since
      photosynthesis has been occurring on earth for about 3 billion years. In order to
      produce any fuel, protons and electrons must be harvested from a species in its
      oxidized form. Photosynthesis uses the only viable source of electrons and
      protons on the scale needed for global energy demands: water. Because artificial
      photosynthesis is a lofty goal, water oxidation, which is a crucial step in the
      process, has been the initial focus. This Account provides an overview of how
      terahertz spectroscopy is used to study electron injection, highlights trends
      from previously published reports, and concludes with a future outlook. It begins
      by exploring similarities and differences between dye-sensitized solar cells
      (DSSCs) for producing electricity and a putative device for splitting water and
      producing a solar fuel. It then identifies two important problems encountered
      when adapting DSSC technology to water oxidation-improper energy matching between
      sensitizer energy levels with the potential for water oxidation and the
      instability of common anchoring groups in water-and discusses steps to address
      them. Emphasis is placed on electron injection from sensitizers to metal oxides
      because this process is the initial step in charge transport. Both the rate and
      efficiency of electron injection are analyzed on a sub-picosecond time scale
      using time-resolved terahertz spectroscopy (TRTS). Bio-inspired pentafluorophenyl
      porphyrins are promising sensitizers because their high reduction potentials are
      compatible with the energy requirements of water oxidation. TRTS of free-base and
      metalated pentafluorophenyl porphyrins reveal inefficient electron injection into
      TiO2 nanoparticles but more efficient electron injection into SnO2 nanoparticles.
      With SnO2, injection time scales depend strongly on the identity of the central
      substituent and are affected by competition with excited-state deactivation
      processes. Heavy or paramagnetic metal ions increase the electron injection time
      scale by roughly one order of magnitude relative to free-base or Zn(2+)
      porphyrins due to the possibility of electron injection from longer-lived, lower
      lying triplet states. Furthermore, electron injection efficiency loosely
      correlates with DSSC performance. The carboxylate anchoring group is commonly
      used to bind DSSC sensitizers to metal oxide surfaces but typically is not stable
      under the aqueous and oxidative conditions required for water oxidation. Electron
      injection efficiency of several water-stable alternatives, including phosphonic
      acid, hydroxamic acid, acetylacetone, and boronic acid, were evaluated using
      TRTS, and hydroxamate was found to perform as well as the carboxylate. The next
      challenge is incorporating a water oxidation catalyst into the design. An early
      example, in which an Ir-based precatalyst is cosensitized with a fluorinated
      porphyrin, reveals decreased electron injection efficiency despite an increase in
      photocurrent. Future research will seek to better understand and address these
      difficulties. 

PMID- 25938859
TI  - Multidimensional evaluation of a mental health court: Adherence to the risk-need
      responsivity model.
AB  - The current study examined the impact of a mental health court (MHC) on mental
      health recovery, criminogenic needs, and recidivism in a sample of 196 community
      based offenders with mental illness. Using a pre-post design, mental health
      recovery and criminogenic needs were assessed at the time of MHC referral and
      discharge. File records were reviewed to score the Level of Service/Risk-Need
      Responsivity instrument (Andrews, Bonta, & Wormith, 2008) to capture criminogenic
      needs, and a coding guide was used to extract mental health recovery information
      at each time point. Only mental health recovery data were available at 12 months
      post-MHC involvement. Recidivism (i.e., charges) was recorded from police records
      over an average follow-up period of 40.67 months post-MHC discharge. Case
      management adherence to the Risk-Need-Responsivity (RNR) model of offender case
      management was also examined. Small but significant improvements were found for
      criminogenic needs and some indicators of mental health recovery for MHC
      completers relative to participants who were prematurely discharged or referred
      but not admitted to the program. MHC completers had a similar rate of general
      recidivism (28.6%) to cases not admitted to MHC and managed by the traditional
      criminal justice system (32.6%). However, MHC case plans only moderately adhered
      to the RNR model. Implications of these results suggest that the RNR model may be
      an effective case management approach for MHCs to assist with decision-making
      regarding admission, supervision intensity, and intervention targets, and that
      interventions in MHC contexts should attend to both criminogenic and mental
      health needs.

PMID- 25938860
TI  - Co-immunoprecipitation of the Mouse Mx1 Protein with the Influenza A Virus
      Nucleoprotein.
AB  - Studying the interaction between proteins is key in understanding their
      function(s). A very powerful method that is frequently used to study interactions
      of proteins with other macromolecules in a complex sample is called co
      immunoprecipitation. The described co-immunoprecipitation protocol allows to
      demonstrate and further investigate the interaction between the antiviral
      myxovirus resistance protein 1 (Mx1) and one of its viral targets, the influenza
      A virus nucleoprotein (NP). The protocol starts with transfected mammalian cells,
      but it is also possible to use influenza A virus infected cells as starting
      material. After cell lysis, the viral NP protein is pulled-down with a specific
      antibody and the resulting immune-complexes are precipitated with protein G
      beads. The successful pull-down of NP and the co-immunoprecipitation of the
      antiviral Mx1 protein are subsequently revealed by western blotting. A
      prerequisite for successful co-immunoprecipitation of Mx1 with NP is the presence
      of N-ethylmaleimide (NEM) in the cell lysis buffer. NEM alkylates free thiol
      groups. Presumably this reaction stabilizes the weak and/or transient NP-Mx1
      interaction by preserving a specific conformation of Mx1, its viral target or an
      unknown third component. An important limitation of co-immunoprecipitation
      experiments is the inadvertent pull-down of contaminating proteins, caused by
      nonspecific binding of proteins to the protein G beads or antibodies. Therefore,
      it is very important to include control settings to exclude false positive
      results. The described co-immunoprecipitation protocol can be used to study the
      interaction of Mx proteins from different vertebrate species with viral proteins,
      any pair of proteins, or of a protein with other macromolecules. The beneficial
      role of NEM to stabilize weak and/or transient interactions needs to be tested
      for each interaction pair individually. 

PMID- 25938861
TI  - Tyrosine kinase inhibitor therapy in chronic myeloid leukemia: update on key
      adverse events.
AB  - Current treatment recommendations for chronic myeloid leukemia (CML) are guided
      by results from multiple clinical trials involving tyrosine kinase inhibitors
      that target BCR-ABL1. Consideration of the unique clinical benefits and potential
      risks associated with each tyrosine kinase inhibitor approved for the treatment
      of CML is crucial for physicians when recommending the most appropriate therapy
      for each patient. Monitoring for and prompt management of adverse events may
      increase adherence to therapy and optimize patient outcomes. Here we provide an
      overview of the efficacy and safety of tyrosine kinase inhibitors approved for
      the treatment of CML, as well as recommendations for the management of key
      adverse events reported with these agents in clinical trials involving patients
      with CML. 

PMID- 25938862
TI  - Isolation and cryopreservation of neonatal rat cardiomyocytes.
AB  - Cell culture has become increasingly important in cardiac research, but due to
      the limited proliferation of cardiomyocytes, culturing cardiomyocytes is
      difficult and time consuming. The most commonly used cells are neonatal rat
      cardiomyocytes (NRCMs), which require isolation every time cells are needed. The
      birth of the rats can be unpredictable. Cryopreservation is proposed to allow for
      cells to be stored until needed, yet freezing/thawing methods for primary
      cardiomyocytes are challenging due to the sensitivity of the cells. Using the
      proper cryoprotectant, dimethyl sulfoxide (DMSO), cryopreservation was achieved.
      By slowly extracting the DMSO while thawing the cells, cultures were obtained
      with viable NRCMs. NRCM phenotype was verified using immunocytochemistry staining
      for alpha-sarcomeric actinin. In addition, cells also showed spontaneous
      contraction after several days in culture. Cell viability after thawing was
      acceptable at 40-60%. In spite of this, the methods outlined allow one to easily
      cryopreserve and thaw NRCMs. This gives researchers a greater amount of
      flexibility in planning experiments as well as reducing the use of animals. 

PMID- 25938863
TI  - Identification of Possible Binding Sites for Morphine and Nicardipine on the
      Multidrug Transporter P-Glycoprotein Using Umbrella Sampling Techniques.
AB  - The multidrug transporter P-glycoprotein (P-gp) is central to the development of
      multidrug resistance in cancer. While residues essential for transport and
      binding have been identified, the location, composition, and specificity of
      potential drug binding sites are uncertain. Here molecular dynamics simulations
      are used to calculate the free energy profile for the binding of morphine and
      nicardipine to P-gp. We show that morphine and nicardipine primarily interact
      with key residues implicated in binding and transport from mutational studies,
      binding at different but overlapping sites within the transmembrane pore. Their
      permeation pathways were distinct but involved overlapping sets of residues. The
      results indicate that the binding location and permeation pathways of morphine
      and nicardipine are not well separated and cannot be considered as unique. This
      has important implications for our understanding of substrate uptake and
      transport by P-gp. Our results are independent of the choice of starting
      structure and consistent with a range of experimental studies. 

PMID- 25938864
TI  - "Epigenethics" in the Neonatal Intensive Care Unit: Conveying Complexity in
      Health Care for Preterm Children.

PMID- 25938865
TI  - Identifying the Location of a Single Protein along the DNA Strand Using Solid
      State Nanopores.
AB  - Solid-state nanopore has been widely studied as an effective tool to detect and
      analyze small biomolecules, such as DNA, RNA, and proteins, at a single molecule
      level. In this study, we demonstrate a rapid identification of the location of
      zinc finger protein (ZFP), which is bound to a specific locus along the length of
      a double-stranded DNA (dsDNA) to a single protein resolution using a low noise
      solid-state nanopore. When ZFP labeled DNAs were driven through a nanopore by an
      externally applied electric field, characteristic ionic current signals arising
      from the passage of the DNA/ZFP complex and bare DNA were detected, which enabled
      us to identify the locations of ZFP binding site. We examined two DNAs with ZFP
      binding sites at different positions and found that the location of the
      additional current drop derived from the DNA/ZFP complex is well-matched with a
      theoretical one along the length of the DNA molecule. These results suggest that
      the protein binding site on DNA can be mapped or that genetic information can be
      read at a single molecule level using solid-state nanopores. 

PMID- 25938866
TI  - Structure-dependent activity of phthalate esters and phthalate monoesters binding
      to human constitutive androstane receptor.
AB  - The present study investigated the human constitutive androstane receptor (CAR)
      binding activities of 23 phthalate esters and 10 phthalate monoesters using a
      fast and sensitive human CAR yeast two-hybrid assay. Of 23 phthalate esters, 16
      were evaluated as positive, and the 10% relative effective concentrations (REC10)
      ranged from 0.28 (BBP) to 29.51 MUM (DEHP), whereas no obvious binding activities
      were found for the phthalate esters having alkyl chains more than six carbons in
      length. Of 10 phthalate monoesters, only monoethyl phthalate (MEP), monoisobutyl
      phthalate (MIBP), and mono-(2-ethyhexyl) tetrabromophthalate (TBMEHP) elicited
      human CAR binding activities. The REC10 values of MEP and MIBP were 4.27 and
      14.13 MUM, respectively, higher than those of their corresponding phthalate
      esters (1.45 MUM for DEP and 0.83 MUM for DIBP), whereas TBMEHP (0.66 MUM) was
      much lower than TBHP (>10(2) MUM). A molecular docking method was performed to
      simulate the interaction modes between phthalates and human CAR, and active
      phthalates were found to lie at almost the same site in the human CAR pocket. The
      docking results suggest that the strong binding of phthalates to human CAR arises
      primarily from hydrophobic interactions, pi-pi interactions, and steric effects
      and that weak hydrogen bonds and weak halogen bonds greatly contribute to the
      high binding activity of TBMEHP. In conclusion, the current study clarified that
      an extensive array of phthalates are activators of human CAR.

PMID- 25938867
TI  - Effects of dissolved organic matter on the co-transport of mineral colloids and
      sorptive contaminants.
AB  - Colloid-facilitated transport of contaminants in the vadose zone has important
      implications to groundwater quality, and has received considerable attention.
      Natural organic matter (NOM) is ubiquitous in subsurface environments, and its
      influence on mineral colloids and solute transport has been well documented.
      However, research on the influence of NOM on colloid-facilitated transport is
      limited. The objective of this paper is to elucidate the effects of NOM on
      colloid-facilitated transport of a radioactive contaminant (Cs-137) within
      partially-saturated sediments. Measurements made with re-packed columns reveal
      that Cs-137 mobility was low when mineral colloids were absent and was unaffected
      by the presence of NOM. The addition of mineral colloids to influent increased Cs
      137 mobility, and effluent Cs-137 was dominated by the colloid-associated form.
      When NOM was added to systems that contained mineral colloids and Cs-137, the
      mobility of Cs-137 further increased. A mathematical model simulating colloid
      facilitated transport showed that NOM increases Cs-137 transport by increasing
      colloid mobility and reducing the rate of Cs-137 adsorption to the porous medium.

PMID- 25938868
TI  - Syntheses And Evaluation Of Asymmetric Curcumin Analogues As Potential
      Multifunctional Agents For The Treatment Of Alzheimer's Disease.
AB  - A series of new asymmetric curcumin analogues were synthesized and evaluated as
      potential multifunctional agents for the treatment of Alzheimer's disease. Our
      results showed that most of these synthetic compounds had better inhibitory
      properties against Abeta aggregation compared with curcumin, and better anti
      oxidative properties compared with the reference compound Trolox through the
      study of oxygen radical absorbance capacity (ORAC). Some compounds showed good
      properties in selectively chelating metal ions such as copper and iron. Besides,
      some compounds were found to be able to dissociate Abeta protein which had
      already aggregated. The structure-activity relationships (SAR) of these synthetic
      compounds were studied. The present investigation indicated that our synthetic
      asymmetric curcumin derivatives could be potential multifunctional agents for the
      treatment of Alzheimer's disease (AD). 

PMID- 25938869
TI  - A Novel Tetradentate Ruthenium(II) Complex Containing Tris(2- Pyridylmethyl)amine
      (tpa) As An Inhibitor Of Beta-amyloid Fibrillation.
AB  - We report herein the synthesis and application of a novel tetradentate
      ruthenium(II) complex 1 containing a tris(2-pyridylmethyl)amine (tpa) ligand as
      an inhibitor of beta-amyloid fibrillogenesis. [Ru(tpa)(bt)]ClO(4) 1 (bt =2
      acetylbenzo[b]thiophene-3-olate) showed significant inhibition of Abeta(1-40)
      peptide aggregation in vitro, which was confirmed by a Thioflavin T assay and
      transmission electron microscopy imaging.

PMID- 25938870
TI  - Inhibitory Activity Of Curcumin Derivatives Towards Metal-free And Metal-induced
      Amyloid-beta Aggregation.
AB  - When Alzheimer's disease (AD) progresses, several pathological features arise
      including accumulation of misfolded protein aggregates [e.g., amyloid-beta
      (Abeta) plaques], metal ion dyshomeostasis, and oxidative stress. These
      characteristics are recently suggested to be interconnected through a potential
      factor, metal-associated Abeta (metal-Abeta) species. The role of metal-Abeta
      species in AD pathogenesis remains unclear, however. To elucidate the
      contribution of metal-Abeta species to AD pathology, as well as to develop small
      molecules as chemical tools and/or theranostic (therapeutic and diagnostic)
      agents for this disease, curcumin (Cur), a natural product from turmeric, and its
      derivatives have been studied towards both metal-free and metal-induced Abeta
      aggregation. Although Cur has indicated anti-amyloidogenic activities and
      antioxidant properties, its biological use has been hindered due to low
      solubility and stability in physiologically relevant conditions. Herein, we
      report the reactivity of Cur and its derivatives (Gd-Cur, a potential multimodal
      Abeta imaging agent; Cur-S, a water soluble derivative of Cur that has
      substitution at the phenolic hydroxyls) with metal-free Abeta and metal-Abeta
      species. Our results and observations indicate that Gd-Cur could modulate Cu(II)
      triggered Abeta aggregation more noticeably over metal-free or Zn(II)-induced
      analogues; however, Cur-S was not observed to noticeably modulate Abeta
      aggregation with and without metal ions. Overall, our studies present information
      that could aid in optimizing the molecular scaffold of Cur for the development of
      chemical tools or theranostics for metal-Abeta species. 

PMID- 25938871
TI  - Small molecules and Alzheimer's disease: misfolding, metabolism and imaging.
AB  - Small molecule interactions with amyloid proteins have had a huge impact in
      Alzheimer&#039;s disease (AD), especially in three specific areas: amyloid
      folding, metabolism and brain imaging. Amyloid plaque amelioration or prevention
      have, until recently, driven drug development, and only a few drugs have been
      advanced for use in AD. Amyloid proteins undergo misfolding and oligomerization
      via intermediates, eventually forming protease resistant amyloid fibrils. These
      fibrils accumulate to form the hallmark amyloid plaques and tangles of AD.
      Amyloid binding compounds can be grouped into three categories, those that: i)
      prevent or reverse misfolding, ii) halt misfolding or trap intermediates, and
      iii) accelerate the formation of stable and inert amyloid fibrils. Such compounds
      include hydralazine, glycosaminoglycans, curcumin, beta sheet breakers,
      catecholamines, and ATP. The versatility of amyloid binding compounds suggests
      that the amyloid structure may serve as a scaffold for the future development of
      sensors to detect such compounds. Metabolic dysfunction is one of the earliest
      pathological features of AD. In fact, AD is often referred to as type 3 diabetes
      due to the presence of insulin resistance in the brain. A recent study indicates
      that altering metabolism improves cognitive function. While metabolic
      reprogramming is one therapeutic avenue for AD, it is more widely used in some
      cancer therapies. FDA approved drugs such as metformin, dichloroacetic acid
      (DCA), and methylene blue can alter metabolism. These drugs can therefore be
      potentially applied in alleviating metabolic dysfunction in AD. Brain imaging has
      made enormous strides over the past decade, offering a new window to the mind.
      Recently, there has been remarkable development of compounds that have the
      ability to image both types of pathological amyloids: tau and amyloid beta. We
      have focused on the low cost, simple to use, near infrared fluorescence (NIRF)
      imaging probes for amyloid beta (Abeta), with specific attention on recent
      developments to further improve contrast, specificity, and sensitivity. With
      advances in imaging technologies, such fluorescent imaging probes will open new
      diagnostic avenues. 

PMID- 25938872
TI  - Inhibition of beta-amyloid Aggregation By Albiflorin, Aloeemodin And
      Neohesperidin And Their Neuroprotective Effect On Primary Hippocampal Cells
      Against beta-amyloid Induced Toxicity.
AB  - Being one of the hallmarks of Alzheimer's disease, beta-amyloid (Abeta)
      aggregates induce complicated neurotoxicity. Evidences show that the underlying
      mechanism of neurotoxicity involves a glutamate receptor subtype, N-methyl-D
      aspartate (NMDA) receptor, an increase in intracellular calcium(II) ion loading
      as well as an elevation in oxidation stress. In this work, among the 35 chemical
      components of Chinese herbal medicines (CHMs) being screened for inhibitors of
      Abeta aggregation, four of them, namely albiflorin, aloeemodin, neohesperidin and
      physcion, were found for the first time to exhibit a potent inhibitory effect on
      Abeta(1-40) and Abeta(1-42) aggregation. Their neuroprotective capability on
      primary hippocampal neuronal cells was also investigated by MTT assay, ROS assay
      and intracellular calcium(II) ion concentration measurement. It was interesting
      to find that physcion was rather toxic to neuronal cells while albiflorin,
      aloeemodin and neohesperidin reduced the toxicity and ROS induced by both
      monomeric and oligomeric Abeta species. In addition, albiflorin was particularly
      powerful in maintaining the intracellular Ca(2+) concentration.

PMID- 25938873
TI  - Dual Inhibition And Monitoring Of Beta-amyloid Fibrillation By A Luminescent
      Iridium(III) Complex.
AB  - In this study, we report the synthesis and application of the novel
      cyclometallated luminescent Ir(III) complex 1 bearing the C^C^C ligand as a probe
      and inhibitor of Abeta fibrillation. We envisage that this kinetically-inert
      Ir(III) complex may be potentially developed as a dual-purpose probe and
      inhibitor of Abeta aggregation for Alzheimer's disease diagnosis and treatment. 

PMID- 25938874
TI  - Glycemic control in twin pregnancies with gestational diabetes: are we improving
      or worsening outcomes?
AB  - OBJECTIVE: To estimate the association between glycemic control and adverse
      outcomes in twin pregnancies with gestational diabetes (GDM). STUDY DESIGN: A
      cohort of patients with twin pregnancies and GDM were identified from one
      maternal-fetal medicine practice from 2005 to 2014. Patients with prepregnancy
      diabetes were excluded. First, outcomes were compared between patients with GDMA1
      and GDMA2 (gestational age at delivery, birthweight, small for gestational age
      (SGA, birthweight <10th percentile), preeclampsia, and cesarean delivery). Then,
      finger stick glucose logs were reviewed and correlated with the risk of SGA and
      preeclampsia. Abnormal finger stick values were defined as: fasting >= 90 mg/dL,
      1-h postprandial >= 140 mg/dL, 2-h postprandial >= 120 mg/dL. RESULTS: Sixty-six
      patients with twin pregnancies and GDM were identified (incidence 9.1%).
      Comparing the 43 patients with GDMA1 to the 23 patients with GDMA2, outcomes were
      similar, aside from patients with GDMA1 having lower birthweight of the smaller
      twin (2184 +/- 519 g versus 2438 +/- 428 g, p = 0.040). The risk of preeclampsia
      was not associated with glycemic control. Patients with SGA had lower mean
      fasting values (83.3 +/- 5.5 versus 87.2 +/- 7.7 mg/dL, p = 0.033), and a lower
      percentage of abnormal fasting values (24.0% versus 36.9%, p = 0.040), abnormal
      post-breakfast values (9.9% versus 27.1%, p = 0.003), and total abnormal values
      (20.1% versus 27.7%, p = 0.055). CONCLUSION: In twin pregnancies with GDM,
      improved glycemic control is not associated with improved outcomes, and is
      associated with a higher risk of SGA. Prospective trials in twin pregnancies
      should be performed to establish goals for glycemic control in twin pregnancies.

PMID- 25938875
TI  - Association of Pioneer Accountable Care Organizations vs traditional Medicare fee
      for service with spending, utilization, and patient experience.
AB  - IMPORTANCE: The Pioneer Accountable Care Organization (ACO) Model aims to drive
      health care organizations to reduce expenditures while improving quality for fee
      for-service (FFS) Medicare beneficiaries. OBJECTIVE: To determine whether FFS
      beneficiaries aligned with Pioneer ACOs had smaller increases in spending and
      utilization than other FFS beneficiaries while retaining similar levels of care
      satisfaction in the first 2 years of the Pioneer ACO Model. DESIGN, SETTING, AND
      PARTICIPANTS: Participants were FFS Medicare beneficiaries aligned with 32 ACOs
      (n = 675,712 in 2012; n = 806,258 in 2013) and a comparison group of alignment
      eligible beneficiaries in the same markets (n = 13,203,694 in 2012; n =
      12,134,154 in 2013). Analyses comprised difference-in-differences multivariable
      regression with Oaxaca-Blinder reweighting to model expenditure and utilization
      outcomes over a 2-year performance period (2012-2013) and 2-year baseline period
      (2010-2011) as well as adjusted analyses of Consumer Assessment of Healthcare
      Providers & Systems (CAHPS) survey responses among random samples of
      beneficiaries in Pioneer ACOs (n = 13,097), FFS (n = 116,255), or Medicare
      Advantage (n = 203,736) for 2012 care. EXPOSURES: Beneficiary alignment with a
      Pioneer ACO in 2012 or 2013. MAIN OUTCOMES AND MEASURES: Medicare spending,
      utilization, and CAHPS domain scores. RESULTS: Total spending for beneficiaries
      aligned with Pioneer ACOs in 2012 or 2013 increased from baseline to a lesser
      degree relative to comparison populations. Differential changes in spending were
      approximately -$35.62 (95% CI, -$40.12 to -$31.12) per-beneficiary-per-month
      (PBPM) in 2012 and -$11.18 (95% CI, -$15.84 to -$6.51) PBPM in 2013, which
      amounted to aggregate reductions in increases of approximately -$280 (95% CI, 
      $315 to -$244) million in 2012 and -$105 (95% CI, -$148 to -$61) million in 2013.
      Inpatient spending showed the largest differential change of any spending
      category (-$14.40 [95% CI, -$17.31 to -$11.49] PBPM in 2012; -$6.46 [95% CI, 
      $9.26 to -$3.66] PBPM in 2013). Changes in utilization of physician services,
      emergency department, and postacute care followed a similar pattern. Compared
      with other Medicare beneficiaries, ACO-aligned beneficiaries reported higher mean
      scores for timely care (77.2 [ACO] vs 71.2 [FFS] vs 72.7 [MA]) and for clinician
      communication (91.9 [ACO] vs 88.3 [FFS] vs 88.7 [MA]). CONCLUSIONS AND RELEVANCE:
      In the first 2 years of the Pioneer ACO Model, beneficiaries aligned with Pioneer
      ACOs, as compared with general Medicare FFS beneficiaries, exhibited smaller
      increases in total Medicare expenditures and differential reductions in
      utilization of different health services, with little difference in patient
      experience.

PMID- 25938876
TI  - Semi-High Throughput Screening for Potential Drought-tolerance in Lettuce
      (Lactuca sativa) Germplasm Collections.
AB  - This protocol describes a method by which a large collection of the leafy green
      vegetable lettuce (Lactuca sativa L.) germplasm was screened for likely drought
      tolerance traits. Fresh water availability for agricultural use is a growing
      concern across the United States as well as many regions of the world. Short-term
      drought events along with regulatory intervention in the regulation of water
      availability coupled with the looming threat of long-term climate shifts that may
      lead to reduced precipitation in many important agricultural regions has
      increased the need to hasten the development of crops adapted for improved water
      use efficiency in order to maintain or expand production in the coming years.
      This protocol is not meant as a step-by-step guide to identifying at either the
      physiological or molecular level drought-tolerance traits in lettuce, but rather
      is a method developed and refined through the screening of thousands of different
      lettuce varieties. The nature of this screen is based in part on the streamlined
      measurements focusing on only three water-stress indicators: leaf relative water
      content, wilt, and differential plant growth following drought-stress. The
      purpose of rapidly screening a large germplasm collection is to narrow the
      candidate pool to a point in which more intensive physiological, molecular, and
      genetic methods can be applied to identify specific drought-tolerant traits in
      either the lab or field. Candidates can also be directly incorporated into
      breeding programs as a source of drought-tolerance traits. 

PMID- 25938877
TI  - Evolution of sediment plumes in the Chesapeake bay and implications of climate
      variability.
AB  - Fluvial sediment transport impacts fisheries, marine ecosystems, and human
      health. In the upper Chesapeake Bay, river-induced sediment plumes are generally
      known as either a monotonic spatial shape or a turbidity maximum. Little is known
      about plume evolution in response to variation in streamflow and extreme
      discharge of sediment. Here we propose a typology of sediment plumes in the upper
      Chesapeake Bay using a 17 year time series of satellite-derived suspended
      sediment concentration. On the basis of estimated fluvial and wind contributions,
      we define an intermittent/wind-dominated type and a continuous type, the latter
      of which is further divided into four subtypes based on spatial features of
      plumes, which we refer to as Injection, Transport, Temporary Turbidity-Maximum,
      and Persistent Turbidity-Maximum. The four continuous types exhibit a consistent
      sequence of evolution within 1 week to 1 month following flood events. We also
      identify a "shift" in typology with increased frequency of Turbidity-Maximum
      types before and after Hurricane Ivan (2004), which implies that extreme events
      have longer-lasting effects upon estuarine suspended sediment than previously
      considered. These results can serve as a diagnostic tool to better predict
      distribution and impacts of estuarine suspended sediment in response to changes
      in climate and land use. 

PMID- 25938879
TI  - Solid particles adsorbed on capillary-bridge-shaped fluid polystyrene surfaces.
AB  - Particles adsorbed on microscopic polystyrene (PS) capillary bridge surfaces were
      observed to investigate their motion under capillary forces arising from a
      nonuniform shape. Capillary bridges were created by placing thin PS films, heated
      above the glass transition temperature (Tg), between two electrodes with an air
      gap between the surface of the PS and the upper electrode. Silica particles, 100
      nm in diameter, were placed on the surface of the PS capillary bridges, and the
      sample was heated above the Tg of PS to enable particle motion. Samples were
      cooled to below Tg, and the locations of the particles were observed using
      scanning electron microscopy. The particles did not preferentially locate around
      the center of the capillary bridge, as predicted by others, but instead
      segregated to the edges. These results indicate that the forces driving particles
      to the three-phase contact line (air/PS/electrode surface) are greater than those
      locating particles around the center. 

PMID- 25938881
TI  - CuSCN-Based Inverted Planar Perovskite Solar Cell with an Average PCE of 15.6%.
AB  - Although inorganic hole-transport materials usually possess high chemical
      stability, hole mobility, and low cost, the efficiency of most of inorganic hole
      conductor-based perovskite solar cells is still much lower than that of the
      traditional organic hole conductor-based cells. Here, we have successfully
      fabricated high quality CH3NH3PbI3 films on top of a CuSCN layer by utilizing a
      one-step fast deposition-crystallization method, which have lower surface
      roughness and smaller interface contact resistance between the perovskite layer
      and the selective contacts in comparison with the films prepared by a
      conventional two-step sequential deposition process. The average efficiency of
      the CuSCN-based inverted planar CH3NH3PbI3 solar cells has been improved to 15.6%
      with a highest PCE of 16.6%, which is comparable to that of the traditional
      organic hole conductor-based cells, and may promote wider application of the
      inexpensive inorganic materials in perovskite solar cells. 

PMID- 25938880
TI  - Calibrated forceps model of spinal cord compression injury.
AB  - Compression injuries of the murine spinal cord are valuable animal models for the
      study of spinal cord injury (SCI) and spinal regenerative therapy. The calibrated
      forceps model of compression injury is a convenient, low cost, and very
      reproducible animal model for SCI. We used a pair of modified forceps in
      accordance with the method published by Plemel et al. (2008) to laterally
      compress the spinal cord to a distance of 0.35 mm. In this video, we will
      demonstrate a dorsal laminectomy to expose the spinal cord, followed by
      compression of the spinal cord with the modified forceps. In the video, we will
      also address issues related to the care of paraplegic laboratory animals. This
      injury model produces mice that exhibit impairment in sensation, as well as
      impaired hindlimb locomotor function. Furthermore, this method of injury produces
      consistent aberrations in the pathology of the SCI, as determined by
      immunohistochemical methods. After watching this video, viewers should be able to
      determine the necessary supplies and methods for producing SCI of various
      severities in the mouse for studies on SCI and/or treatments designed to mitigate
      impairment after injury. 

PMID- 25938882
TI  - A possible cooperative structural transition of DNA in the 0.25-2.0 pN range.
AB  - The measured effective torsional rigidities of single twisted DNAs under various
      tensions conflict with theoretical predictions of Moroz and Nelson (MN) at low
      forces in the 0.25-2.0 pN range. However, MN theory was recently shown to agree
      well with effective torsional rigidities obtained from simulations, indicating
      that MN theory is valid down to 0.25 pN for a filament with a constant intrinsic
      torsional rigidity. Here MN theory is used with an assumed persistence length, 50
      nm, to obtain the force-dependent intrinsic torsional rigidity of the filament at
      each force from its measured effective torsional rigidity. The resulting values
      rise ~1.8-fold with increasing force from 0.25 to 2.0 pN. Unexpected behavior of
      the relative extensions of the untwisted DNAs of Mosconi et al. is noted, and
      ascribed to a small increase in contour length with force over the 0.18-2.0 pN
      range. The variations of both the intrinsic torsional rigidity and rise per base
      pair (bp) with force are suggested to arise from a force-induced shift of a
      cooperative equilibrium between two conformations with different rises per bp. A
      two-state nearest-neighbor model is formulated, and ranges of optimal parameters
      are determined by fitting the model to the experimental differences in rise per
      bp as a function of force. Optimal adjustment of the torsion elastic constants of
      the two states enables the same optimal model(s) with fixed parameters to provide
      reasonably good fits of the experimental torsion elastic constant data. The
      results reconcile single-molecule measurements on DNAs under tension with
      numerous results from fluorescence polarization anisotropy, topoisomer
      distributions, X-ray scattering of DNAs with attached gold colloids, and other
      kinds of measurements. 

PMID- 25938883
TI  - An astrocyte-dependent mechanism for neuronal rhythmogenesis.
AB  - Communication between neurons rests on their capacity to change their firing
      pattern to encode different messages. For several vital functions, such as
      respiration and mastication, neurons need to generate a rhythmic firing pattern.
      Here we show in the rat trigeminal sensori-motor circuit for mastication that
      this ability depends on regulation of the extracellular Ca(2+) concentration
      ([Ca(2+)]e) by astrocytes. In this circuit, astrocytes respond to sensory stimuli
      that induce neuronal rhythmic activity, and their blockade with a Ca(2+) chelator
      prevents neurons from generating a rhythmic bursting pattern. This ability is
      restored by adding S100beta, an astrocytic Ca(2+)-binding protein, to the
      extracellular space, while application of an anti-S100beta antibody prevents
      generation of rhythmic activity. These results indicate that astrocytes regulate
      a fundamental neuronal property: the capacity to change firing pattern. These
      findings may have broad implications for many other neural networks whose
      functions depend on the generation of rhythmic activity. 

PMID- 25938884
TI  - A SNP in the HTT promoter alters NF-kappaB binding and is a bidirectional genetic
      modifier of Huntington disease.
AB  - Cis-regulatory variants that alter gene expression can modify disease
      expressivity, but none have previously been identified in Huntington disease
      (HD). Here we provide in vivo evidence in HD patients that cis-regulatory
      variants in the HTT promoter are bidirectional modifiers of HD age of onset. HTT
      promoter analysis identified a NF-kappaB binding site that regulates HTT promoter
      transcriptional activity. A non-coding SNP, rs13102260:G > A, in this binding
      site impaired NF-kappaB binding and reduced HTT transcriptional activity and HTT
      protein expression. The presence of the rs13102260 minor (A) variant on the HD
      disease allele was associated with delayed age of onset in familial cases,
      whereas the presence of the rs13102260 (A) variant on the wild-type HTT allele
      was associated with earlier age of onset in HD patients in an extreme case-based
      cohort. Our findings suggest a previously unknown mechanism linking allele
      specific effects of rs13102260 on HTT expression to HD age of onset and have
      implications for HTT silencing treatments that are currently in development. 

PMID- 25938886
TI  - Effects of High-Dose Vitamin D Supplementation on Metabolic Status and Pregnancy
      Outcomes in Pregnant Women at Risk for Pre-Eclampsia.
AB  - This study was designed to assess the beneficial effects of high-dose
      (cholecalciferol) vitamin D supplementation on metabolic profiles and pregnancy
      outcomes among pregnant women at risk for pre-eclampsia. This randomized double
      blind placebo-controlled clinical trial was performed among 60 pregnant women at
      risk for pre-eclampsia according to abnormal uterine artery Doppler waveform.
      Subjects were randomly divided into 2 groups to receive 50 000 IU vitamin D
      supplements (n=30) or receive placebo (n=30) every 2 weeks from 20 to 32 weeks of
      gestation. Fasting blood samples were taken at baseline study and 12 weeks after
      the intervention to quantify relevant variables. Newborn's anthropometric
      measurements were determined. Pregnant women who received cholecalciferol
      supplements had significantly increased serum 25-hydroxyvitamin D concentrations
      (+17.92+/-2.28 vs. +0.27+/-3.19 ng/ml, p<0.001) compared with the placebo. The
      administration of cholecalciferol supplements, compared with the placebo,
      resulted in significant differences in serum insulin concentrations (+1.08+/-6.80
      vs. +9.57+/-10.32 MUIU/ml, p<0.001), homeostasis model of assessment-insulin
      resistance (HOMA-IR) (+0.19+/-1.47 vs. +2.10+/-2.67, p<0.001), homeostatic model
      assessment-beta cell function (HOMA-B) (+5.82+/-29.58 vs. +39.81+/-38.00,
      p<0.001) and quantitative insulin sensitivity check index (QUICKI) score (
      0.009+/-0.03 vs. -0.04+/-0.03, p=0.004). Furthermore, cholecalciferol
      supplemented pregnant women had increased HDL-cholesterol concentrations (+2.67
      +/- 8.83 vs. -3.23+/-7.76 mg/dl, p=0.008) compared with the placebo. Finally,
      cholecalciferol supplementation led to a significant rise in plasma total
      antioxidant capacity (TAC) concentrations (+79.00+/-136.69 vs. -66.91+/-176.02
      mmol/l, p=0.001) compared with the placebo. Totally, the administration of
      cholecalciferol supplements among pregnant women at risk for pre-eclampsia for 12
      weeks had favorable effects on insulin metabolism parameters, serum HDL
      cholesterol, and plasma TAC concentrations.

PMID- 25938885
TI  - Spine pruning drives antipsychotic-sensitive locomotion via circuit control of
      striatal dopamine.
AB  - Psychiatric and neurodevelopmental disorders may arise from anomalies in long
      range neuronal connectivity downstream of pathologies in dendritic spines.
      However, the mechanisms that may link spine pathology to circuit abnormalities
      relevant to atypical behavior remain unknown. Using a mouse model to
      conditionally disrupt a critical regulator of the dendritic spine cytoskeleton,
      the actin-related protein 2/3 complex (Arp2/3), we report here a molecular
      mechanism that unexpectedly reveals the inter-relationship of progressive spine
      pruning, elevated frontal cortical excitation of pyramidal neurons and striatal
      hyperdopaminergia in a cortical-to-midbrain circuit abnormality. The main
      symptomatic manifestations of this circuit abnormality are psychomotor agitation
      and stereotypical behaviors, which are relieved by antipsychotics. Moreover, this
      antipsychotic-responsive locomotion can be mimicked in wild-type mice by
      optogenetic activation of this circuit. Collectively these results reveal
      molecular and neural-circuit mechanisms, illustrating how diverse pathologies may
      converge to drive behaviors relevant to psychiatric disorders. 

PMID- 25938888
TI  - Impact of Regional Lymph Node Dissection on Disease Specific Survival in Adrenal
      Cortical Carcinoma.
AB  - Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. The
      purpose of this study is to evaluate the impact of a more extensive regional
      lymph node dissection (LND) has on survival in ACC patients in the United States.
      Patients >= 15 years of age without distant metastases who underwent surgical
      intervention for primary ACC were identified from the SEER18 registry from 1988
      2009. Patients were divided into 2 groups: having a regional LND (>= 5 LNs
      removed) vs. no-LND (0-4 LNs removed). Overall survival (OS) and disease specific
      survival (DSS) were compared between groups. Of 259 patients with complete data
      on nodal resection, 243 (93.8%) underwent no-LND and 16 (6.2%) LND. There was no
      difference in age, sex, metastases, or ENSAT stage between groups. However, LND
      patients had larger tumors (p=0.004), and more frequently underwent en-bloc
      surgery (p=0.002). One- and 3-year OS and DSS did not differ between groups. In a
      cox regression model, performance of a regional LND did not significantly
      influence DSS. However, female gender (HR: 1.67, CI: 1.04-2.69, p=0.033) and
      later stage (stage III-HR: 4.78, CI: 1.14-20.00, p=0.032) or positive LNs (HR:
      5.92, CI: 2.05-17.08, p=0.001) were risk factors for worse DSS. Regional LND may
      not improve DSS or OS in nonmetastatic ACC patients undergoing adrenalectomy. It
      remains controversial as an essential part of the surgical management for ACC and
      deserves further investigation in a larger, prospective study. However, regional
      LND should still be considered for staging and prognostic purposes and to
      standardize surgical care.

PMID- 25938887
TI  - Low Frequency of MKRN3 Mutations in Central Precocious Puberty Among Korean
      Girls.
AB  - Mutations of MKRN3, the gene encoding makorin RING-finger protein 3, lead to
      central precocious puberty (CPP). The aim of this study was to investigate
      mutations of the MKRN3 gene in Korean girls with CPP. Two hundred-sixty Korean
      girls with idiopathic CPP were included. Auxological and endocrine parameters
      were measured, and the entire MKRN3 gene was directly sequenced. MKRN3 gene
      analysis revealed one novel nonsense mutation (p.Gln281 *) and 6 missense
      variants (p.Ile100Phe, p.Gly196Val, p.Ile204Thr, p.Gln226Pro, p.Lys233Asn, and
      p.Ser396Arg). The novel nonsense mutation (p.Gln281 *) was a heterozygous C>T
      nucleotide change (c.841C>T) predicted to result in a truncated protein due to a
      premature stop codon in the MKRN3 gene. The nonsense mutation (p.Gln281 *) was
      only identified in one of the girls and her younger brother. Compared to previous
      reports on MKRN3 mutations in familial and sporadic cases of CPP, the present
      study reveals a relatively low number of MKRN 3 mutations in Korean girls with
      CPP. Larger samples of children with CPP and MKRN3 mutations are necessary in
      order to clarify whether the clinical course of puberty may differ as compared to
      idiopathic CPP. 

PMID- 25938889
TI  - Melatonin Modulates the Immune System Response and Inflammation in Diabetic Rats
      Experimentally-Induced by Alloxan.
AB  - Diabetes mellitus (DM) is a metabolic disease, which causes an increase in the
      proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin
      1beta (IL-1beta), and also proliferation of monocyte chemotactic protein. In the
      present study, the potential effects of melatonin on proinflammatory cytokines,
      hematological values, and lymphoid tissues were investigated in diabetic rats. In
      the study, 36 male rats were randomly divided into 4 groups as follows: Control,
      Mel (melatonin), DM, and DM-Mel. For 15 days, an isotonic saline solution was
      given to the Control and DM groups; melatonin was administered to the Mel and DM
      Mel groups intraperitoneally. At the end of the study, all animals were
      sacrificed by drawing the blood from their hearts under deep anesthesia. Samples
      of the spleen, thymus, and lymph nodes were fixed in 10% formaldehyde for
      histologic analysis. Increases in proinflammatory serum cytokine concentrations,
      mast cells, and total white blood cell counts as well as tissue destruction in
      the lymphoid organs were determined in the DM group via biochemical,
      hematological, and histologic analyses. However, the findings for the DM-Mel
      group revealed decreases in serum IL-1beta concentration and mast cell densities,
      and destructions in lymphoid tissues by the melatonin administration. The present
      study suggests that melatonin treatment may control immune system regulation and
      inhibit the production of proinflammatory cytokines and tissue mast cell
      accumulation by preventing the destruction of lymphoid organs in the diabetic
      process. 

PMID- 25938891
TI  - Immobilization of Enzymes by Electrochemical and Chemical Oxidative
      Polymerization of L-DOPA to Fabricate Amperometric Biosensors and Biofuel Cells.
AB  - Electrochemical/chemical oxidative synthesis and biosensing/biofuel cell
      applications of poly(L-DOPA) (PD) are studied versus polydopamine (PDA) as a
      recent hotspot biomaterial. The enzyme electrode developed by coelectrodeposition
      of PD and glucose oxidase (GOx), uricase, or tyrosinase shows biosensing
      performance superior to that of the corresponding PDA-based enzyme electrode. The
      chemical oxidative polymerization of L-DOPA (PDC) by NaAuCl4 in GOx-containing
      neutral aqueous solution is used to immobilize GOx and gold nanoparticles
      (AuNPs). The thus-prepared chitosan (CS)/GOx-PDC-AuNPs/Au(plate)/Au electrode
      working in the first-generation biosensing mode responds linearly to glucose
      concentration with a sensitivity of 152 MUA mM(-1) cm(-2), which is larger than
      those of the CS/GOx-PDAC-AuNPs/Au(plate)/Au electrode, the CS/GOx-poly(3
      anilineboronic acid) (PABA)-AuNPs/Au(plate)/Au electrode, and the most reported
      GOx-based enzyme electrodes. This PDC-based enzyme electrode also works well in
      the second-generation biosensing mode and as an excellent bioanode in biofuel
      cell construction, probably because PD as an amino acid polymer has the higher
      biocompatibility and the more favorable affinity to the enzyme than PDA. The PD
      material of great convenience in synthesis, outstanding biocompatibility for
      preparing high-performance bionanocomposites, and strong capability of
      multifunctional coatings on many surfaces may find wide applications in
      diversified fields including biotechnology and surface-coating.

PMID- 25938892
TI  - Production and characterization of a camelid single domain antibody-urease enzyme
      conjugate for the treatment of cancer.
AB  - A novel immunoconjugate (L-DOS47) was developed and characterized as a
      therapeutic agent for tumors expressing CEACAM6. The single domain antibody
      AFAIKL2, which targets CEACAM6, was expressed in the Escherichia coli BL21 (DE3)
      pT7-7 system. High purity urease (HPU) was extracted and purified from Jack bean
      meal. AFAIKL2 was activated using N-succinimidyl [4-iodoacetyl] aminobenzoate
      (SIAB) as the cross-linker and then conjugated to urease. The activation and
      conjugation reactions were controlled by altering pH. Under these conditions, the
      material ratio achieved conjugation ratios of 8-11 antibodies per urease
      molecule, the residual free urease content was practically negligible (<2%), and
      high purity (>95%) L-DOS47 conjugate was produced using only ultradiafiltration
      to remove unreacted antibody and hydrolyzed cross-linker. L-DOS47 was
      characterized by a panel of analytical techniques including SEC, IEC, Western
      blot, ELISA, and LC-MS(E) peptide mapping. As the antibody-urease conjugate ratio
      increased, a higher binding signal was observed. The specificity and cytotoxicity
      of L-DOS47 was confirmed by screening in four cell lines (BxPC-3, A549, MCF7, and
      CEACAM6-transfected H23). BxPC-3, a CEACAM6-expressing cell line was found to be
      most susceptible to L-DOS47. L-DOS47 is being investigated as a potential
      therapeutic agent in human phase I clinical studies for nonsmall cell lung
      cancer. 

PMID- 25938878
TI  - Intergenerational transmission of self-regulation: A multidisciplinary review and
      integrative conceptual framework.
AB  - This review examines mechanisms contributing to the intergenerational
      transmission of self-regulation. To provide an integrated account of how self
      regulation is transmitted across generations, we draw from over 75 years of
      accumulated evidence, spanning case studies to experimental approaches, in
      literatures covering developmental, social, and clinical psychology, and
      criminology, physiology, genetics, and human and animal neuroscience (among
      others). First, we present a taxonomy of what self-regulation is and then examine
      how it develops--overviews that guide the main foci of the review. Next, studies
      supporting an association between parent and child self-regulation are reviewed.
      Subsequently, literature that considers potential social mechanisms of
      transmission, specifically parenting behavior, interparental (i.e., marital)
      relationship behaviors, and broader rearing influences (e.g., household chaos) is
      considered. Finally, evidence that prenatal programming may be the starting point
      of the intergenerational transmission of self-regulation is covered, along with
      key findings from the behavioral and molecular genetics literatures. To integrate
      these literatures, we introduce the self-regulation intergenerational
      transmission model, a framework that brings together prenatal, social/contextual,
      and neurobiological mechanisms (spanning endocrine, neural, and genetic levels,
      including gene-environment interplay and epigenetic processes) to explain the
      intergenerational transmission of self-regulation. This model also incorporates
      potential transactional processes between generations (e.g., children's self
      regulation and parent-child interaction dynamics that may affect parents' self
      regulation) that further influence intergenerational processes. In pointing the
      way forward, we note key future directions and ways to address limitations in
      existing work throughout the review and in closing. We also conclude by noting
      several implications for intervention work.

PMID- 25938893
TI  - Sun-to-Wheels Exergy Efficiencies for Bio-Ethanol and Photovoltaics.
AB  - The two main paths to power vehicles with sunlight are to use photosynthesis to
      grow biomass, converting to a liquid fuel for an internal combustion engine or to
      generate photovoltaic electricity that powers the battery of an electric vehicle.
      While the environmental attributes of these two paths have been much analyzed,
      prior studies consider the current state of technology. Technologies for biofuel
      and photovoltaic paths are evolving; it is critical to consider how progress
      might improve environmental performance. We address this challenge by assessing
      the current and maximum theoretical exergy efficiencies of bioethanol and
      photovoltaic sun-to-wheels process chains. The maximum theoretical efficiency is
      an upper bound stipulated by physical laws. The current net efficiency to produce
      motive power from silicon photovoltaic modules is estimated at 5.4%, much higher
      than 0.03% efficiency for corn-based ethanol. Flat-plate photovoltaic panels also
      have a much higher theoretical maximum efficiency than a C4 crop plant, 48%
      versus 0.19%. Photovoltaic-based power will always be vastly more efficient than
      a terrestrial crop biofuel. Providing all mobility in the U.S. via crop biofuels
      would require 130% of arable land with current technology and 20% in the
      thermodynamic limit. Comparable values for photovoltaic-based power are 0.7% and
      0.081%, respectively. 

PMID- 25938894
TI  - Design, Surface Treatment, Cellular Plating, and Culturing of Modular Neuronal
      Networks Composed of Functionally Inter-connected Circuits.
AB  - The brain operates through the coordinated activation and the dynamic
      communication of neuronal assemblies. A major open question is how a vast
      repertoire of dynamical motifs, which underlie most diverse brain functions, can
      emerge out of a fixed topological and modular organization of brain circuits.
      Compared to in vivo studies of neuronal circuits which present intrinsic
      experimental difficulties, in vitro preparations offer a much larger possibility
      to manipulate and probe the structural, dynamical and chemical properties of
      experimental neuronal systems. This work describes an in vitro experimental
      methodology which allows growing of modular networks composed by spatially
      distinct, functionally interconnected neuronal assemblies. The protocol allows
      controlling the two-dimensional (2D) architecture of the neuronal network at
      different levels of topological complexity. A desired network patterning can be
      achieved both on regular cover slips and substrate embedded micro electrode
      arrays. Micromachined structures are embossed on a silicon wafer and used to
      create biocompatible polymeric stencils, which incorporate the negative features
      of the desired network architecture. The stencils are placed on the culturing
      substrates during the surface coating procedure with a molecular layer for
      promoting cellular adhesion. After removal of the stencils, neurons are plated
      and they spontaneously redirected to the coated areas. By decreasing the inter
      compartment distance, it is possible to obtain either isolated or interconnected
      neuronal circuits. To promote cell survival, cells are co-cultured with a
      supporting neuronal network which is located at the periphery of the culture
      dish. Electrophysiological and optical recordings of the activity of modular
      networks obtained respectively by using substrate embedded micro electrode arrays
      and calcium imaging are presented. While each module shows spontaneous global
      synchronizations, the occurrence of inter-module synchronization is regulated by
      the density of connection among the circuits. 

PMID- 25938895
TI  - A Fast and Reliable Pipeline for Bacterial Transcriptome Analysis Case study:
      Serine-dependent Gene Regulation in Streptococcus pneumoniae.
AB  - Gene expression and its regulation are very important to understand the behavior
      of cells under different conditions. Various techniques are used nowadays to
      study gene expression, but most are limited in terms of providing an overall
      picture of the expression of the whole transcriptome. DNA microarrays offer a
      fast and economic research technology, which gives a full overview of global gene
      expression and have a vast number of applications including identification of
      novel genes and transcription factor binding sites, characterization of
      transcriptional activity of the cells and also help in analyzing thousands of
      genes (in a single experiment). In the present study, the conditions for
      bacterial transcriptome analysis from cell harvest to DNA microarray analysis
      have been optimized. Taking into account the time, costs and accuracy of the
      experiments, this technology platform proves to be very useful and universally
      applicabale for studying bacterial transcriptomes. Here, we perform DNA
      microarray analysis with Streptococcus pneumoniae as a case-study by comparing
      the transcriptional responses of S. pneumoniae grown in the presence of varying L
      serine concentrations in the medium. Total RNA was isolated by using a Macaloid
      method using an RNA isolation kit and the quality of RNA was checked by using an
      RNA quality check kit. cDNA was prepared using reverse transcriptase and the cDNA
      samples were labelled using one of two amine-reactive fluorescent dyes. Homemade
      DNA microarray slides were used for hybridization of the labelled cDNA samples
      and microarray data were analyzed by using a cDNA microarray data pre-processing
      framework (Microprep). Finally, Cyber-T was used to analyze the data generated
      using Microprep for the identification of statistically significant
      differentially expressed genes. Furthermore, in-house built software packages
      (PePPER, FIVA, DISCLOSE, PROSECUTOR, Genome2D) were used to analyze data. 

PMID- 25938896
TI  - SURGICAL AND NON-SURGICAL THERAPY OF OBSTRUCTIVE SLEEP APNEA SYNDROME IN
      CHILDREN.
AB  - Interventions of paediatric obstructive sleep apnea syndrome are complex, varied
      and multidisciplinary. The goal of the treatment is to restore optimal breathing
      during the night and to relieve associated symptoms. Evidence suggests that the
      surgical intervention with removal of the tonsils and adenoids will lead to
      significant improvements in the most incomplicated cases, as recently reported
      from a meta-analysis. However, post-operative persistence of this syndrome in
      paediatric population is more frequent than expected, which supports the idea of
      the complexity of this syndrome. Adenotomy alone may not be sufficient in
      children with OSAS, because it does not address oropharyngeal obstruction
      secondary to tonsillar hyperplasia. Continuous positive airway pressure can
      effectively treat this syndrome in selected groups of children, improving both
      nocturnal and daytime symptoms, but poor adherence is a limiting factor. For this
      reason, CPAP is not recommended as first-line therapy for OSAS when
      adenotonsillectomy is an option. It is now being investigated the incorporation
      of nonsurgical approaches for milder forms and for residual OSAS after surgical
      intervention. Althought adeno-tonsillar hypertrophy is the most common for OSAS
      in children; obesity is emerging as an equally important etiological factor.
      Therefore an intensive weight reduction program and adequate sleep hygiene are
      also important lifestyle changes that may be very effective in mitigating the
      symptoms of this syndrome. Pharmacological therapy (leukotriene antagonists,
      topical nasal steroids) is usually use for mild forms of OSAS and in children
      with associated allergic diseases. Special orthodontic treatment and
      oropharyngeal exercises are a relatively new and promising alternative
      therapeutic modality used in selected groups of children with OSAS. 

PMID- 25938897
TI  - NANOTECHNOLOGY - NEW TRENDS IN THE TREATMENT OF BRAIN TUMOURS.
AB  - High grade gliomas are some of the deadliest human tumours. Conventional
      treatments such as surgery, radiotherapy and chemotherapy have only a limited
      effect. Nowadays, resection is the common treatment of choice and although new
      approaches, such as perioperative magnetic resonance imaging or fluorescent
      microscopy have been developed, the survival rate of diagnosed patients is still
      very low. The inefficacy of conventional methods has led to the development of
      new strategies and the significant progress of nanotechnology in recent years.
      These platforms can be used either as novel imaging tools or to improve
      anticancer drug delivery into tumours while minimizing its distribution and
      toxicity in healthy tissues. Amongst the new nanotechnology platforms used for
      delivery into the brain tissue are: polymeric nanoparticles, liposomes,
      dendrimers, nanoshells, carbon nanotubes, superparamagnetic nanoparticles and
      nucleic acid based nanoparticles (DNA, RNA interference [RNAi] and antisense
      oligonucleotides [ASO]). These nanoparticles have been applied in the delivery of
      small molecular weight drugs as well as macromolecules - proteins, peptides and
      genes. The unique properties of these nanoparticles, such as surface charge,
      particle size, composition and ability to modify their surface with tissue
      recognition ligands and antibodies, improve their biodistribution and
      pharmacokinetics. All of the above mentioned characteristics make of
      nanoplatforms a very suitable tool for its use in targeted, personalized
      medicine, where they could possibly carry large doses of therapeutic agents
      specifically into malignant cells while avoiding healthy cells. This review poses
      new possibilities in the large field of nanotechnology with special interest in
      the treatment of high grade brain tumours. 

PMID- 25938898
TI  - INTRA-SCLERAL PARATHALAMUS IMPLANT: EFFICACY AND SAFETY IN RABBIT EYES.
AB  - PURPOSE: A variety of anti-glaucomatous shunt designs have been proposed so far.
      This study evaluates the feasibility of a novel shunt design, the intra-scleral
      parathalamus implant (IPI), in a rabbit eye model. METHODS: Ten healthy albino
      rabbits were included. Measurements of the IOP, using TonoPenXL, as well as
      ocular rigidity (OR) and aqueous outflow facility (AO), using a previously
      described methodology, were performed in both eyes of each animal. Subsequently,
      the IPI was implanted at the left eye of all animals whereas the right eye served
      as control. Measurements of IOP were repeated at weekly intervals for 2 months
      postoperatively whereas measurements of OR and AO were repeated at the 1st and
      2nd postoperative week. RESULTS: The IOP decreased significantly whereas the AO
      increased significantly postoperatively at the operated eyes. A significant
      postoperative decrease in OR was also recorded at the operated eyes. Respective
      differences at the fellow eyes were statistically not significant. Two animals
      developed postoperative complications and were excluded from follow-up.
      CONCLUSIONS: Results imply that the implantation of the IPI is feasible in rabbit
      eyes with significant favorable effects on the IOP, AO and OR.

PMID- 25938899
TI  - ASPIRIN RESISTANCE IN NEUROVASCULAR DISEASES.
AB  - INTRODUCTION: The issue of resistance to antiplatelet therapy has raised many
      questions in the area of neurovascular diseases. The first objective of this work
      was to determine the prevalence of aspirin resistance in neurovascular patients
      with clinical non-responsiveness to aspirin treatment and a high-risk of
      atherothrombotic complications using two interpretable and independent methods
      (aggregation and PFA 100). The second objective was to find the correlation
      between both assays and to evaluate the results in groups at risk for various
      cerebrovascular diseases. MATERIAL AND METHODS: Laboratory tests of aspirin
      resistance were performed in 79 patients with clinical non-responsiveness to
      aspirin treatment suffering from neurovascular diseases. Patients were divided
      into the two groups: expected low risk for aspirin resistance due to the first
      manifestation of a neurovascular disease (n = 34) and expected high risk due to
      the second clinical manifestation of a neurovascular disease (n = 45). RESULTS:
      The prevalence of aspirin resistance in both groups combined as determined by the
      PFA-100 and CPG techniques were 50.6% and 17.7%, respectively. No correlation was
      found between the two techniques. CONCLUSIONS: No significant prevalence of
      aspirin resistance was demonstrated by either method despite the heterogeneous
      pathophysiological mechanisms. However, we are presently unable to provide an
      accurate opinion on the value of laboratory test result or routine monitoring in
      clinical neurology.

PMID- 25938900
TI  - LOW-GRADE MYOFIBROBLASTIC SARCOMA OF THE LARYNX: CASE REPORT AND REVIEW OF
      LITERATURE.
AB  - Low-grade myofibroblastic sarcoma (LGMS) is a very rare, atypical myofibroblastic
      tumor with fibromatosis-like features with predilection mostly in head and neck
      region. LGMS occurs primarily in adult patients with a slight male predominance.
      Only few cases of LGMS affecting the larynx have been reported in literature to
      this date. We describe a case of low-grade myofibroblastic sarcoma of the larynx
      in a 40-year-old male patient. The clinicopathological characteristics,
      immunohistochemical findings and treatment are discussed. 

PMID- 25938901
TI  - LATE-ONSET CAPSULAR BAG DISTENSION SYNDROME: A REPORT OF TWO CASES.
AB  - Capsular bag distension syndrome is a very rare complication of cataract surgery.
      Most cases occur after uneventful phacoemulsification with continuous curvilinear
      capsulorhexis and implantation of an intraocular lens in the capsular bag. The
      entity presents with reduction of visual acuity and myopic shift in the early-to
      late postoperative period. Characteristic findings include the distension of the
      capsular bag due to the accumulation of milky material and the forward
      displacement of the intraocular lens. We present two cases with an unusually
      delayed presentation of 6 and 8 years respectively following phacoemulsification,
      and describe their successful management with Nd:YAG laser posterior capsulotomy.

PMID- 25938902
TI  - A Network Meta-analysis of Outcomes of 7 Surgical Treatments for Distal Radius
      Fractures.
AB  - To determinate the optimal treatment for distal radius fractures (DRF) by
      comparing the pin-track infection (PTI) rates in patients treated with 7 surgical
      techniques [bridging external fixation (EF), nonbridging EF, K-wire fixation,
      plaster fixation, dorsal plating, dorsal and volar plating, and volar plating].
      After an exhaustive search of electronic databases for relevant published
      studies, high-quality randomized controlled trails were selected for the present
      network meta-analysis based on predefined selection criteria. Statistical
      analyses of the extracted data were conducted using Stata 12.0 software. After
      careful selection, 19 randomized controlled trails were included in our network
      meta-analysis and contained a combined total of 1805 subjects who underwent
      various surgical procedures. The network meta-analysis results showed that
      compared with bridging EF for treating DRF, the nonbridging EF, plaster fixation,
      volar plating, and dorsal and volar plating showed statistically significant
      differences in PTI rates. Importantly, the surface under the cumulative ranking
      curve values of the surgical interventions revealed that the PTI rates of plaster
      fixation and of dorsal and volar plating were the lowest, suggesting that these 2
      surgical techniques are optimal for DRFs treatment, compared with the other
      methods. Our results suggest that plaster fixation and dorsal and volar plating
      are the best surgical treatments for DRFs compared with 5 other most common
      techniques. Thus, plaster fixation and dorsal and volar plating emerge as the
      most effective and credible treatments in consideration of PTI rates.

PMID- 25938903
TI  - gamma-H2AX induced by linear alkylbenzene sulfonates is due to deoxyribonuclease
      1 translocation to the nucleus via actin disruption.
AB  - Phosphorylation of histone H2AX (gamma-H2AX) occurs following formation of DNA
      double strand breaks (DSBs). Other types of DNA damage also generate DSBs through
      DNA replication and repair, leading to the production of gamma-H2AX. In the
      present study, we demonstrated that linear alkylbenzene sulfonates (LAS), the
      most widely used and non-genotoxic anionic surfactants, could generate gamma-H2AX
      via a novel pathway. Breast adenocarcinoma MCF-7 cells were treated with five
      kinds of LAS with alkyl chains ranging from 10 to 14 carbon units (C10-C14LAS).
      The generation of DSBs and subsequent production of gamma-H2AX increased in a
      manner that depended on the number of carbon units in LAS. gamma-H2AX could also
      be generated with non-cytotoxic doses of LAS and was independent of the cell
      cycle, indicating the non-apoptotic and DNA replication-independent formation of
      DSBs. The generation of gamma-H2AX could be attenuated by EGTA and ZnCl2,
      deoxyribonuclease-1 (DNase I) inhibitors, as well as by the knockdown of DNase I.
      LAS weakened the interaction between DNase I and actin, and the enhanced release
      of DNase I was dependent on the number of carbon units in LAS. DNase I released
      by the LAS treatment translocated to the nucleus, in which DNase I attacked DNA
      and generated gamma-H2AX. These results suggested that the LAS-induced generation
      of gamma-H2AX could be attributed to the translocation of DNase I to the nucleus
      through the disruption of actin, and not to LAS-induced DNA damage. 

PMID- 25938904
TI  - Transmission of clonal chromosomal abnormalities in human hematopoietic stem and
      progenitor cells surviving radiation exposure.
AB  - In radiation-induced acute myeloid leukemia (rAML), clonal chromosomal
      abnormalities are often observed in bone marrow cells of patients, suggesting
      that their formation is crucial in the development of the disease. Since rAML is
      considered to originate from hematopoietic stem and progenitor cells (HSPC), we
      investigated the frequency and spectrum of radiation-induced chromosomal
      abnormalities in human CD34(+) cells. We then measured stable chromosomal
      abnormalities, a possible biomarker of leukemia risk, in clonally expanded cell
      populations which were grown for 14 days in a 3D-matrix (CFU-assay). We compared
      two radiation qualities used in radiotherapy, sparsely ionizing X-rays and
      densely ionizing carbon ions (29 and 60-85 keV/MUm, doses between 0.5 and 4 Gy).
      Only a negligible number of de novo arising, unstable aberrations (<= 0.05
      aberrations/cell, 97% breaks) were measured in the descendants of irradiated
      HSPC. However, stable aberrations were detected in colonies formed by irradiated
      HSPC. All cells of the affected colonies exhibited one or more identical
      aberrations, indicating their clonal origin. The majority of the clonal
      rearrangements (92%) were simple exchanges such as translocations (77%) and
      pericentric inversions (15%), which are known to contribute to the development of
      rAML. Carbon ions were more efficient in inducing cell killing (maximum of ~ 30
      35% apoptotic cells for 2 Gy carbon ions compared to ~ 25% for X-rays) and
      chromosomal aberrations in the first cell-cycle after exposure (~ 70% and ~ 40%
      for 1 Gy of carbon ions and X-rays, respectively), with a higher fraction of non
      transmissible aberrations. In contrast, for both radiation qualities the
      percentage of clones with chromosomal abnormalities was similar (40%). Using the
      frequency of colonies with clonal aberrations as a surrogate marker for the
      leukemia risk following radiotherapy of solid tumors, charged particle therapy is
      not expected to lead to an increased risk of leukemia in patients.

PMID- 25938905
TI  - Radiochemical determination of rare Earth elements in proton-irradiated lead
      bismuth eutectic.
AB  - Various types of proton-irradiated lead-bismuth eutectic (LBE) samples from the
      MEGAPIE prototype spallation target were analyzed concerning their content of
      (148)Gd, (173)Lu, and (146)Pm by use of alpha- and gamma-spectrometry. A
      radiochemical separation procedure was developed to isolate the lanthanide
      fraction and to prepare thin samples for alpha-ray measurement. The results prove
      a substantial depletion of these three elements in bulk samples, whereas
      accumulation on the LBE/steel-interfaces was observed. The amount of material
      accumulated on surfaces was roughly estimated by relating the values measured on
      the sample surfaces to the total surface of the inner target walls. The amount of
      (148)Gd, (173)Lu, and (146)Pm was then quantified by summing up the contributions
      from every sample type. The results show a reasonable agreement with theoretical
      predictions. The obtained results are of utmost importance for the evaluation of
      the performance of high-power spallation targets, especially concerning the
      residual nuclide production, the physicochemical behavior of the produced
      radionuclides during operation, and in terms of an intermediate or final
      disposal. 

PMID- 25938906
TI  - Towards understanding nuclear pore complex architecture and dynamics in the age
      of integrative structural analysis.
AB  - Determining the functional architecture of the nuclear pore complex, that remains
      only partially understood, requires bridging across different length scales.
      Recent technological advances in quantitative and cross-linking mass
      spectrometry, super-resolution fluorescence microscopy and electron microscopy
      have enormously accelerated the integration of different types of data into
      coherent structural models. Moreover, high-resolution structural analysis of
      nucleoporins and their in vitro reconstitution into complexes is now facilitated
      by the use of thermostable orthologs. In this review we highlight how the
      application of such technologies has led to novel insights into nuclear pore
      architecture and to a paradigm shift. Today nuclear pores are not anymore seen as
      static facilitators of nucleocytoplasmic transport but ensembles of multiple
      overlaying functional states that are involved in various cellular processes. 

PMID- 25938908
TI  - Emerging properties of nuclear RNP biogenesis and export.
AB  - RNA biology has recently seen an explosion of data due to advances in RNA
      sequencing, proteomic, and RNA imaging technologies. In this review, we highlight
      progress that has been made using these approaches in the area of nuclear RNP
      biogenesis and export. Excitingly, the ability to collect quantitative data at
      the 'omics' scale combined with measurements of transcription, decay, and
      transport kinetics is providing the information needed to address RNP biogenesis
      at a systems level. We believe this to be a necessary and critical next step that
      will lead to a better understanding of how RNP quality, diversity, and fate
      emerge from a defined set of nuclear RNP assembly and maturation steps. 

PMID- 25938909
TI  - Enantiopure Trans-4,5-Disubstituted 2-Imidazolidinones via Copper(I)-Catalyzed
      Ring Opening of 1,1'-DiBoc-2,2'-Biaziridine with Grignard Reagents.
AB  - The copper-catalyzed ring opening of chiral-pool-derived 1,1'-diBoc-2,2'
      biaziridine with Grignard reagents affords enantiopure 2-imidazolidinones in a
      desymmetrizing, cascade process involving the Boc protecting group. This
      divergent strategy provides reaction-ready, N-differentiated products and allows
      two C-C bond constructions concurrent to imidazolidinone formation. A variety of
      alkyl, cyclic, and aryl Grignard reagents are tolerated in reasonable to good
      yields. 

PMID- 25938907
TI  - The Yin and Yang of R-loop biology.
AB  - RNA performs diverse functions in cells, directing translation, modulating
      transcription and catalyzing enzymatic reactions. Remarkably RNA can also anneal
      to its genomic template co- or post-transcriptionally to generate an RNA-DNA
      hybrid and a displaced single-stranded DNA. These unusual nucleic acid structures
      are called R-loops. Studies in the last decades concentrated on the detrimental
      effects of R-loop formation, particularly on genome stability. In fact, R-loops
      are thought to play a role in several human diseases like cancer and
      neurodegenerative syndromes. But recent data has revealed that R-loops can also
      have a positive impact on cell processes, like regulating gene expression,
      chromosome structure and DNA repair. Here we summarize our current understanding
      of the formation and dissolution of R-loops, and discuss their negative and
      positive impact on genome structure and function. 

PMID- 25938910
TI  - Curcumin Prevents Palmitoylation of Integrin beta4 in Breast Cancer Cells.
AB  - Curcumin has been shown to mitigate cancer phenotypes such as invasive migration,
      proliferation, and survival by disrupting numerous signaling pathways. Our
      previous studies showed that curcumin inhibits integrin beta4 (ITG beta4)
      dependent migration by blocking interaction of this integrin with growth factor
      receptors in lipid rafts. In the current study, we investigated the possibility
      that curcumin inhibits ITG beta4 palmitoylation, a post-translational
      modification required for its lipid raft localization and signaling activity. We
      found that the levels of ITG beta4 palmitoylation correlated with the invasive
      potential of breast cancer cells, and that curcumin effectively reduced the
      levels of ITG beta4 palmitoylation in invasive breast cancer cells. Through
      studies of ITG beta4 palmitoylation kinetics, we concluded curcumin suppressed
      palmitoylation independent of growth factor-induced phosphorylation of key ITG
      beta4 Ser and Tyr residues. Rather, curcumin blocked autoacylation of the
      palmitoyl acyltransferase DHHC3 that is responsible for ITG beta4 palmitoylation.
      Moreover, these data reveal that curcumin is able to prevent the palmitoylation
      of a subset of proteins, but not indiscriminately bind to and block all cysteines
      from modifications. Our studies reveal a novel paradigm for curcumin to account
      for much of its biological activity, and specifically, how it is able to suppress
      the signaling function of ITG beta4 in breast cancer cells. 

PMID- 25938911
TI  - Dermal exposure assessment to pesticides in farming systems in developing
      countries: comparison of models.
AB  - In the field of occupational hygiene, researchers have been working on developing
      appropriate methods to estimate human exposure to pesticides in order to assess
      the risk and therefore to take the due decisions to improve the pesticide
      management process and reduce the health risks. This paper evaluates dermal
      exposure models to find the most appropriate. Eight models (i.e., COSHH, DERM,
      DREAM, EASE, PHED, RISKOFDERM, STOFFENMANAGER and PFAM) were evaluated according
      to a multi-criteria analysis and from these results five models (i.e., DERM,
      DREAM, PHED, RISKOFDERM and PFAM) were selected for the assessment of dermal
      exposure in the case study of the potato farming system in the Andean highlands
      of Vereda La Hoya, Colombia. The results show that the models provide different
      dermal exposure estimations which are not comparable. However, because of the
      simplicity of the algorithm and the specificity of the determinants, the DERM,
      DREAM and PFAM models were found to be the most appropriate although their
      estimations might be more accurate if specific determinants are included for the
      case studies in developing countries. 

PMID- 25938912
TI  - Association between Fine Particulate Air Pollution and Daily Clinic Visits for
      Migraine in a Subtropical City: Taipei, Taiwan.
AB  - This study was undertaken to determine whether there was an association between
      fine particle (PM2.5) levels and daily clinic visits for migraine in Taipei,
      Taiwan. Daily clinic visits for migraine and ambient air pollution data for
      Taipei were obtained for the period from 2006-2011. The odds ratio of clinic
      visits was estimated using a case-crossover approach, controlling for weather
      variables, day of the week, seasonality, and long-term time trends. Generally, no
      significant associations between PM2.5 levels and migraine visits were observed
      on cool days. On warm days, however, for the single pollutant model (without
      adjustment for other pollutants), increased clinic visits for migraine were
      significantly associated with PM2.5 levels, with an interquartile range (IQR)
      rise associated with a 13% (95% CI = 8%-19%) elevation in number of migraine
      visits. In bi-pollutant model, PM2.5 remained significant after the inclusion of
      sulfur dioxide (SO2) or ozone (O3) on warm days. This study provides evidence
      that higher levels of PM2.5 increase the risk of clinic visits for migraine in
      Taipei, Taiwan.

PMID- 25938913
TI  - Greek college students and psychopathology: new insights.
AB  - BACKGROUND: College students' mental health problems include depression, anxiety,
      panic disorders, phobias and obsessive compulsive thoughts. AIMS: To investigate
      Greek college students' psychopathology. METHODS: During the initial evaluation,
      638 college students were assessed through the following psychometric
      questionnaires: (a) Eysenck Personality Questionnaire (EPQ); (b) The Symptom
      Checklist-90 (SCL-90); (c) The Beck Depression Inventory (BDI); (d) State-Trait
      Anxiety Inventory (STAI). RESULTS: State anxiety and trait anxiety were
      correlated, to a statistically significant degree, with the family status of the
      students (p = 0.024) and the past visits to the psychiatrist (p = 0.039)
      respectively. The subscale of psychoticism is significantly related with the
      students' origin, school, family status and semester. The subscale of neuroticism
      is significantly related with the students' school. The subscale of extraversion
      is significantly related with the students' family psychiatric history. Students,
      whose place of origin is Attica, have on average higher scores in somatization,
      phobic anxiety and paranoid ideation than the other students. Students from
      abroad have, on average, higher scores in interpersonal sensitivity and
      psychoticism than students who hail from other parts of Greece. The majority of
      the students (79.7%) do not suffer from depression, according to the Beck's
      depression inventory scale. CONCLUSIONS: Anxiety, somatization, personality
      traits and depression are related with the students' college life.

PMID- 25938914
TI  - Beneficial Effect of Higher Dietary Fiber Intake on Plasma HDL-C and TC/HDL-C
      Ratio among Chinese Rural-to-Urban Migrant Workers.
AB  - Research has shown that high-dose supplemental dietary fiber intake has
      beneficial effects on cardiovascular risk factors. To clarify such a
      relationship, we examined the association between daily dietary fiber intake and
      plasma lipids using a cross-sectional design including 1034 (M 502, F 532) rural
      to-urban workers in China. We found a dose-response relationship between
      increased dietary fiber intakes and increase of HDL cholesterol in male workers.
      There was also a dose-response relationship between increased dietary fiber
      intake and decreased total cholesterol to HDL cholesterol (TC/HDL-C) ratio in
      both male and female workers, after adjusting for potential confounders (p for
      trend, all p < 0.05). When the average dietary fiber intake increased from less
      than 18 g/day to over 30 g/day, the average HDL cholesterol level increased by
      10.1%, and the TC/HDL-C ratio decreased by 14.4% for males (p = 0.020) and by
      11.1% for females (p = 0.048). In conclusion, higher daily dietary fiber
      consumption is associated with beneficial effect on cholesterol for rural-to
      urban workers in China, suggesting its potential beneficial effect on decreasing
      the risk of cardiovascular diseases. 

PMID- 25938915
TI  - Mesocrystals in Biominerals and Colloidal Arrays.
AB  - Mesocrystals, which originally was a term to designate superstructures of
      nanocrystals with a common crystallographic orientation, have now evolved to a
      materials concept. The discovery that many biominerals are mesocrystals generated
      a large research interest, and it was suggested that mesocrystals result in
      better mechanical performance and optical properties compared to single
      crystalline structures. Mesocrystalline biominerals are mainly found in spines or
      shells, which have to be mechanically optimized for protection or as a load
      bearing skeleton. Important examples include red coral and sea urchin spine as
      well as bones. Mesocrystals can also be formed from purely synthetic components.
      Biomimetic mineralization and assembly have been used to produce mesocrystals,
      sometimes with complex hierarchical structures. Important examples include the
      fluorapatite mesocrystals with gelatin as the structural matrix, and
      mesocrystalline calcite spicules with impressive strength and flexibility that
      could be synthesized using silicatein protein fibers as template for calcium
      carbonate deposition. Self-assembly of nanocrystals can also result in
      mesocrystals if the nanocrystals have a well-defined size and shape and the
      assembly conditions are tuned to allow the nanoparticles to align
      crystallographically. Mesocrystals formed by assembly of monodisperse metallic,
      semiconducting, and magnetic nanocrystals are a type of colloidal crystal with a
      well-defined structure on both the atomic and mesoscopic length
      scale.Mesocrystals typically are hybrid materials between crystalline
      nanoparticles and interspacing amorphous organic or inorganic layers. This
      structure allows to combine disparate materials like hard but brittle
      nanocrystals with a soft and ductile amorphous material, enabling a mechanically
      optimized structural design as realized in the sea urchin spicule. Furthermore,
      mesocrystals can combine the properties of individual nanocrystals like the
      optical quantum size effect, surface plasmon resonance, and size dependent
      magnetic properties with a mesostructure and morphology tailored for specific
      applications. Indeed, mesocrystals composed of crystallographically aligned
      polyhedral or rodlike nanocrystals with anisotropic properties can be materials
      with strongly directional properties and novel collective emergent properties. An
      additional advantage of mesocrystals is that they can combine the properties of
      nanoparticles with a structure on the micro- or macroscale allowing for much
      easier handling.

PMID- 25938916
TI  - Predicting peptide-mediated interactions on a genome-wide scale.
AB  - We describe a method to predict protein-protein interactions (PPIs) formed
      between structured domains and short peptide motifs. We take an integrative
      approach based on consensus patterns of known motifs in databases, structures of
      domain-motif complexes from the PDB and various sources of non-structural
      evidence. We combine this set of clues using a Bayesian classifier that reports
      the likelihood of an interaction and obtain significantly improved prediction
      performance when compared to individual sources of evidence and to previously
      reported algorithms. Our Bayesian approach was integrated into PrePPI, a
      structure-based PPI prediction method that, so far, has been limited to
      interactions formed between two structured domains. Around 80,000 new domain
      motif mediated interactions were predicted, thus enhancing PrePPI's coverage of
      the human protein interactome. 

PMID- 25938917
TI  - Functional MRI reveals different response inhibition between adults and children
      with ADHD.
AB  - OBJECTIVE: Attention-deficit hyperactivity disorder (ADHD) has been recognized as
      a disorder of executive function, and a number of functional MRI (fMRI) studies
      have been conducted to investigate the altered brain activation patterns between
      ADHD patients and healthy controls. However, the findings across different
      studies have been inconsistent, and the different neural mechanisms between
      adults and children with ADHD remain unclear. The aim of this study was to
      perform a meta-analysis of fMRI studies to further investigate and compare the
      abnormalities in adults and children with ADHD during motor response inhibition.
      METHOD: Activation likelihood estimation (ALE) was used to investigate brain
      activation differences between ADHD patients and controls, and a subtraction meta
      analysis was performed to compare adult and child patients. RESULTS: Twenty-three
      studies met the inclusion criteria. Meta-analysis using ALE detected
      significantly decreased activation during response inhibition in ADHD in the
      supplementary motor area, insula, caudate, and precentral gyrus, as well as
      increased activation in the postcentral gyrus, inferior frontal gyrus, and
      precuneus. The activation decreases in the right caudate were greater in child
      ADHD patients than adult ADHD patients. CONCLUSIONS: This meta-analysis
      identified dysfunction in several areas of the motor inhibition network that may
      play a role in the abnormal neural mechanisms of response inhibition in ADHD. The
      comparison of child and adult subgroups raises the possibility that the
      persistence of functional abnormalities of the caudate may be an important factor
      in whether ADHD persists.

PMID- 25938919
TI  - Correction to Renzi et al. (2014).

PMID- 25938918
TI  - Neuropsychological performance in adolescent marijuana users with co-occurring
      alcohol use: A three-year longitudinal study.
AB  - OBJECTIVE: The effect of adolescent marijuana use on brain development remains
      unclear despite relaxing legal restrictions, decreased perceived harm, and
      increasing use rates among youth. The aim of this 3-year prospective study was to
      evaluate the long-term neurocognitive effects of adolescent marijuana use.
      METHOD: Adolescent marijuana users with concomitant alcohol use (MJ + ALC, n =
      49) and control teens with limited substance use histories (CON, n = 59) were
      given neuropsychological and substance use assessments at project baseline, when
      they were ages 16-19. They were then reassessed 18 and 36 months later. Changes
      in neuropsychological measures were evaluated with repeated measures analysis of
      covariance (ANCOVA), controlling for lifetime alcohol use, and examined the
      effects of group, time, and group by time interactions on cognitive functioning.
      RESULTS: MJ + ALC users performed significantly worse than controls, across time
      points, in the domains of complex attention, memory, processing speed, and
      visuospatial functioning (ps <.05). Earlier age of marijuana use onset was
      associated with poorer processing speed and executive functioning by the 3-year
      follow-up (ps <=.02). CONCLUSIONS: Frequent marijuana use throughout adolescence
      and into young adulthood appeared linked to worsened cognitive performance.
      Earlier age of onset appears to be associated with poorer neurocognitive outcomes
      that emerge by young adulthood, providing further support for the notion that the
      brain may be uniquely sensitive to frequent marijuana exposure during the
      adolescent phase of neurodevelopment. Continued follow-up of adolescent marijuana
      users will determine the extent of neural recovery that may occur if use abates.

PMID- 25938920
TI  - Ductal carcinoma in situ: treatment or active surveillance?
AB  - Ductal carcinoma-in situ (DCIS) is a non-obligate precursor for invasive breast
      cancer and concern exists regarding the potential for overdiagnosis and
      overtreatment as the natural history of DCIS progression to invasive breast
      cancer may never occur or take decades in some cases. Preoperative systemic
      therapy window studies may provide powerful clues to best uncover which
      particular DCIS lesions respond to systemic therapies and allow for future
      selective personalized management recommendations. One of the main challenges for
      instituting active surveillance for DCIS with vacuum-assisted core needle biopsy
      alone and no surgery is concern for leaving untreated occult invasive carcinoma.
      Breast MRI lacks sufficient diagnostic ability to differentiate pure DCIS from
      invasive cancer with DCIS. Current novel randomized trials investigating active
      surveillance versus active management are described. Multigene expression assays
      may someday prove useful in stratifying patients at increased risk for
      progression to invasive breast cancer in the absence of surgery. 

PMID- 25938921
TI  - Defects in the Self-Assembly of Block Copolymers and Their Relevance for Directed
      Self-Assembly.
AB  - Block copolymer self-assembly provides a platform for fabricating dense, ordered
      nanostructures by encoding information in the chemical architecture of
      multicomponent macromolecules. Depending on the volume fraction of the components
      and chain topology, these macromolecules form a variety of spatially periodic
      microphases in thermodynamic equilibrium. The kinetics of self-assembly, however,
      often results in initial morphologies with defects, and the subsequent ordering
      is protracted. Different strategies have been devised to direct the self-assembly
      of copolymer materials by external fields to align and perfect the self-assembled
      nanostructures. Understanding and controlling the thermodynamics of defects,
      their response to external fields, and their dynamics is important because
      applications in microelectronics either require extremely low defect densities or
      aim at generating specific defects at predetermined locations to fabricate
      irregular device-oriented structures for integrated circuits. In this review, we
      discuss defect morphologies of block copolymers in the bulk and thin films,
      highlighting (a) analogies to and differences from defects in other crystalline
      materials, (b) the stability of defects and their dynamics, and (c) the influence
      of external fields.

PMID- 25938922
TI  - Thermoelectric Properties of Solution Synthesized Nanostructured Materials.
AB  - Thermoelectric nanocomposites made by solution synthesis and compression of
      nanostructured chalcogenides could potentially be low-cost, scalable alternatives
      to traditional solid-state synthesized materials. We review the progress in this
      field by comparing the power factor and/or the thermoelectric figure of merit,
      ZT, of four classes of materials: (Bi,Sb)2(Te,Se)3, PbTe, ternary and quaternary
      copper chalcogenides, and silver chalcogenides. We also discuss the thermal
      conductivity reduction associated with multiphased nanocomposites. The ZT of the
      best solution synthesized materials are, in several cases, shown to be equal to
      or greater than the corresponding bulk materials despite the generally reduced
      mobility associated with solution synthesized nanocomposites. For the solution
      synthesized materials with the highest performance, the synthesis and processing
      conditions are summarized to provide guidance for future work.

PMID- 25938923
TI  - Mouse Naive CD4+ T Cell Isolation and In vitro Differentiation into T Cell
      Subsets.
AB  - Antigen inexperienced (naive) CD4(+) T cells undergo expansion and
      differentiation to effector subsets at the time of T cell receptor (TCR)
      recognition of cognate antigen presented on MHC class II. The cytokine signals
      present in the environment at the time of TCR activation are a major factor in
      determining the effector fate of a naive CD4(+) T cell. Although the cytokine
      environment during naive T cell activation may be complex and involve both
      redundant and opposing signals in vivo, the addition of various cytokine
      combinations during naive CD4(+) T cell activation in vitro can readily promote
      the establishment of effector T helper lineages with hallmark cytokine and
      transcription factor expression. Such differentiation experiments are commonly
      used as a first step for the evaluation of targets believed to promote or inhibit
      the development of certain CD4(+) T helper subsets. The addition of mediators,
      such as signaling agonists, antagonists, or other cytokines, during the
      differentiation process can also be used to study the influence of a particular
      target on T cell differentiation. Here, we describe a basic protocol for the
      isolation of naive T cells from mouse and the subsequent steps necessary for
      polarizing naive cells to various T helper effector lineages in vitro. 

PMID- 25938924
TI  - Bio-Inspired Structural Colors Produced via Self-Assembly of Synthetic Melanin
      Nanoparticles.
AB  - Structural colors arising from interactions of light with submicron scale
      periodic structures have been found in many species across all taxa, serving
      multiple biological functions including sexual signaling, camouflage, and
      aposematism. Directly inspired by the extensive use of self-assembled melanosomes
      to produce colors in avian feathers, we set out to synthesize and assemble
      polydopamine-based synthetic melanin nanoparticles in an effort to fabricate
      colored films. We have quantitatively demonstrated that synthetic melanin
      nanoparticles have a high refractive index and broad absorption spanning across
      the UV-visible range, similar to natural melanins. Utilizing a thin-film
      interference model, we demonstrated the coloration mechanism of deposited films
      and showed that the unique optical properties of synthetic melanin nanoparticles
      provide advantages for structural colors over other polymeric nanoparticles
      (i.e., polystyrene colloidal particles). 

PMID- 25938925
TI  - Intracranial Hemorrhage and Deep T-Wave Inversions.

PMID- 25938926
TI  - Eyes on new product development.

PMID- 25938928
TI  - The Ann Arbor Criteria for Appropriate Urinary Catheter Use in Hospitalized
      Medical Patients: Results Obtained by Using the RAND/UCLA Appropriateness Method.
AB  - Interventions to reduce urinary catheter use involve lists of "appropriate"
      indications developed from limited evidence without substantial multidisciplinary
      input. Implementing these lists, however, is challenging given broad
      interpretation of indications, such as "critical illness." To refine criteria for
      appropriate catheter use-defined as use in which benefits outweigh risks-the
      RAND/UCLA Appropriateness Method was applied. After reviewing the literature, a
      15-member multidisciplinary panel of physicians, nurses, and specialists in
      infection prevention rated scenarios for catheter use as appropriate,
      inappropriate, or of uncertain appropriateness by using a standardized,
      multiround rating process. The appropriateness of Foley catheters, intermittent
      straight catheters (ISCs), and external condom catheters for hospitalized adults
      on medical services was assessed in 299 scenarios, including urinary retention,
      incontinence, wounds, urine volume measurement, urine sample collection, and
      comfort. The scenarios included patient-specific issues, such as difficulty
      turning and catheter placement challenges. The panel rated 105 Foley scenarios
      (43 appropriate, 48 inappropriate, 14 uncertain), 97 ISC scenarios (15
      appropriate, 66 inappropriate, 16 uncertain), and 97 external catheter scenarios
      (30 appropriate, 51 inappropriate, 16 uncertain). The refined criteria clarify
      that Foley catheters are appropriate for measuring and collecting urine only when
      fluid status or urine cannot be assessed by other means; specify that patients in
      the intensive care unit (ICU) need specific medical indications for catheters
      because ICU location alone is not an appropriate indication; and recognize that
      Foley and external catheters may be pragmatically appropriate to manage urinary
      incontinence in select patients. These new appropriateness criteria can inform
      large-scale collaborative and bedside efforts to reduce inappropriate urinary
      catheter use. 

PMID- 25938929
TI  - In pursuit of appropriate urinary catheter indications: details matter.

PMID- 25938927
TI  - Mass spectrometric approaches to study protein structure and interactions in
      lyophilized powders.
AB  - Amide hydrogen/deuterium exchange (ssHDX-MS) and side-chain photolytic labeling
      (ssPL-MS) followed by mass spectrometric analysis can be valuable for
      characterizing lyophilized formulations of protein therapeutics. Labeling
      followed by suitable proteolytic digestion allows the protein structure and
      interactions to be mapped with peptide-level resolution. Since the protein
      structural elements are stabilized by a network of chemical bonds from the main
      chains and side-chains of amino acids, specific labeling of atoms in the amino
      acid residues provides insight into the structure and conformation of the
      protein. In contrast to routine methods used to study proteins in lyophilized
      solids (e.g., FTIR), ssHDX-MS and ssPL-MS provide quantitative and site-specific
      information. The extent of deuterium incorporation and kinetic parameters can be
      related to rapidly and slowly exchanging amide pools (N fast, N slow) and
      directly reflects the degree of protein folding and structure in lyophilized
      formulations. Stable photolytic labeling does not undergo back-exchange, an
      advantage over ssHDX-MS. Here, we provide detailed protocols for both ssHDX-MS
      and ssPL-MS, using myoglobin (Mb) as a model protein in lyophilized formulations
      containing either trehalose or sorbitol.

PMID- 25938930
TI  - Ecological network analysis for a virtual water network.
AB  - The notions of virtual water flows provide important indicators to manifest the
      water consumption and allocation between different sectors via product
      transactions. However, the configuration of virtual water network (VWN) still
      needs further investigation to identify the water interdependency among different
      sectors as well as the network efficiency and stability in a socio-economic
      system. Ecological network analysis is chosen as a useful tool to examine the
      structure and function of VWN and the interactions among its sectors. A balance
      analysis of efficiency and redundancy is also conducted to describe the
      robustness (RVWN) of VWN. Then, network control analysis and network utility
      analysis are performed to investigate the dominant sectors and pathways for
      virtual water circulation and the mutual relationships between pairwise sectors.
      A case study of the Heihe River Basin in China shows that the balance between
      efficiency and redundancy is situated on the left side of the robustness curve
      with less efficiency and higher redundancy. The forestation, herding and fishing
      sectors and industrial sectors are found to be the main controllers. The network
      tends to be more mutualistic and synergic, though some competitive relationships
      that weaken the virtual water circulation still exist. 

PMID- 25938931
TI  - Selective tuning of the self-assembly and gelation of a hydrophilic poloxamine by
      cyclodextrins.
AB  - Complexes formed between cyclodextrins (CDs) and polymers - pseudopolyrotaxanes
      (PPRs) - are the starting point of a multitude of supramolecular structures,
      which are proposed for a wide range of biomedical and technological applications.
      In this work, we investigate the complexation of a range of cyclodextrins with
      Tetronic T1307, a four-arm block copolymer of poly(ethylene oxide)-poly(propylene
      oxide)-poly(ethylene oxide) with a pH-responsive central ethylene diamine spacer,
      and its impact on micellization and the sol-gel transition. At low
      concentrations, small-angle neutron scattering (SANS) combined with dynamic light
      scattering (DLS) measurements show the presence of spherical micelles with a
      highly hydrated shell and a dehydrated core. Increasing the temperature leads to
      more compact micelles and larger aggregation numbers, whereas acidic conditions
      induce a shrinking of the micelles, with fewer unimers per micelle and a more
      hydrated corona. At high concentrations, T1307 undergoes a sol-gel transition,
      which is suppressed at pH below the pKa,1 (4.6). SANS data analysis reveals that
      the gels result from a random packing of the micelles, which have an increasing
      aggregation number and increasingly dehydrated shell and hydrated core with the
      temperature. Native CDs (alpha, beta, gamma-CD) can complex T1307, resulting in
      the precipitation of a PPR. Instead, modified CDs compete with micellization to
      an extent that is critically dependent on the nature of the substitution. (1)H
      and ROESY NMR combined with SANS demonstrate that dimethylated beta-CD can thread
      onto the polymer, preferentially binding to the PO units, thus hindering self
      aggregation by solubilizing the hydrophobic block. The various CDs are able to
      modulate the onset of gelation and the extent of the gel phase, and the effect
      correlates with the ability of the CDs to disrupt the micelles, with the
      exception of a sulfated sodium salt of beta-CD, which, while not affecting the
      CMT, is able to fully suppress the gel phase. 

PMID- 25938933
TI  - Reconstruction of Digital Skin Defects with the Free Wrist Crease Flap.
AB  - BACKGROUND: Soft-tissue digital defects frequently need to be covered by a flap
      rather than a skin graft. In hand surgery, functional preservation and aesthetic
      appearance are often as important as procedural efficacy. OBJECTIVE: We present
      our clinical experience with reconstruction of digital skin defects with the free
      wrist crease flap. METHODS: From January 2012 to September 2013, 14 digits of 14
      patients (10 males, 4 females) were included for evaluation. The procedure was
      performed with brachial plexus block anesthesia. The superficial palmar branch of
      the radial artery, a subcutaneous superficial vein, and the palmar cutaneous
      branch of the median nerve were included in the free wrist crease flap. The flaps
      were used to reconstruct the skin defect of injured digits through microvascular
      anastomosis, and donor sites were closed primarily. RESULTS: Postoperative follow
      up time ranged from 3 to 25 months. All digital deformities were corrected, all
      flaps survived completely without ischemia, and none were aesthetically bulky.
      The area of free wrist crease flaps ranged from 2.5 to 5.0 cm by 2.0 to 3.1 cm.
      Slight wound infections appeared in two cases. Venous crisis occurred in one
      case, but it was successfully addressed after vascular exploration and
      reanastomosis. Sensation determined by static two-point discrimination measured
      in these flaps 2 months postsurgery was "good" at a mean 9.7 +/- 2.1 mm (range, 6
      14 mm). The mean motion range of the distal interphalangeal joint and proximal
      interphalangeal joint was 23.4 +/- 6.9 degrees (0-42 degrees) and 75.8 +/- 22.1
      degrees (0-98 degrees) preoperatively. The mean motion range of the distal
      interphalangeal joint recovered to 40.3 +/- 5.7 degrees (36-42 degrees), and that
      of the proximal interphalangeal joint was 90.3 +/- 15.3 degrees (85-98 degrees)
      postoperatively. Both joints reached normal motion angle and difference was
      statistically significant preoperatively and postoperatively (p < 0.05). The mean
      disabilities of arm and shoulder (DASH) score was 6.8 +/- 3.4 (0-15), and there
      was statistically significant difference when compared with the preoperative
      score of 13.5 +/- 4.3 (3-19) (p < 0.05). CONCLUSION: We found the free wrist
      crease flap to be an ideal solution for reconstruction of skin defects of digits.

PMID- 25938932
TI  - Effect of Thymosin beta4 on the Survival of Random Skin Flaps in Rats.
AB  - BACKGROUND: Random skin flaps can be used throughout the hands and fingers.
      Thymosin beta4 can increase blood flow and reduce ischemia-reperfusion injury;
      the study was undertaken to investigate the effect of thymosin beta4 on the
      survival of random skin flaps. METHODS: A total of 45 male Sprague-Dawley rats
      were used and subjected to a random-pattern skin flaps operation. Rats were
      randomly divided into three groups: a control group (group A: intraperitoneal
      injection of saline, 5 mg/kg/d) and two treatment groups (group B:
      intraperitoneal injection of thymosin beta4, a single 5 mg/kg dose per day) and
      (group C: intraperitoneal injection of thymosin beta4, 5 mg/kg dose twice per
      day). The flap surviving area was measured after 7 days, and tissue samples were
      stained with hematoxylin and eosin. Vascular endothelial growth factor (VEGF)
      expression was determined using immunohistochemical methods. Superoxide dismutase
      (SOD) activity and malondialdehyde (MDA) content were examined with kits.
      RESULTS: Thymosin beta4 significantly reduced the necrotic area in the treatment
      groups after 7 days compared with the control group, and the rats receiving
      thymosin beta4 5 mg/kg twice per day had the highest survival rate. VEGF
      expression and SOD activity markedly increased in the treatment groups compared
      with the control group, whereas MDA levels were lower in the treatment groups
      than in the control group. CONCLUSION: Thymosin beta4 may have a dose-dependent
      effect to promote the survival of random skin flaps.

PMID- 25938934
TI  - Preparation, imaging, and quantification of bacterial surface motility assays.
AB  - Bacterial surface motility, such as swarming, is commonly examined in the
      laboratory using plate assays that necessitate specific concentrations of agar
      and sometimes inclusion of specific nutrients in the growth medium. The
      preparation of such explicit media and surface growth conditions serves to
      provide the favorable conditions that allow not just bacterial growth but
      coordinated motility of bacteria over these surfaces within thin liquid films.
      Reproducibility of swarm plate and other surface motility plate assays can be a
      major challenge. Especially for more "temperate swarmers" that exhibit motility
      only within agar ranges of 0.4%-0.8% (wt/vol), minor changes in protocol or
      laboratory environment can greatly influence swarm assay results. "Wettability",
      or water content at the liquid-solid-air interface of these plate assays, is
      often a key variable to be controlled. An additional challenge in assessing
      swarming is how to quantify observed differences between any two (or more)
      experiments. Here we detail a versatile two-phase protocol to prepare and image
      swarm assays. We include guidelines to circumvent the challenges commonly
      associated with swarm assay media preparation and quantification of data from
      these assays. We specifically demonstrate our method using bacteria that express
      fluorescent or bioluminescent genetic reporters like green fluorescent protein
      (GFP), luciferase (lux operon), or cellular stains to enable time-lapse optical
      imaging. We further demonstrate the ability of our method to track competing
      swarming species in the same experiment. 

PMID- 25938935
TI  - Circadian clock-coupled lung cellular and molecular functions in chronic airway
      diseases.
AB  - Airway diseases are associated with abnormal circadian rhythms of lung function,
      reflected in daily changes of airway caliber, airway resistance, respiratory
      symptoms, and abnormal immune-inflammatory responses. Circadian rhythms are
      generated at the cellular level by an autoregulatory feedback loop of interlocked
      transcription factors collectively referred to as clock genes. The molecular
      clock is altered by cigarette smoke, LPS, and bacterial and viral infections in
      mouse and human lungs and in patients with chronic airway diseases. Stress
      mediated post-translational modification of molecular clock proteins, brain and
      muscle aryl hydrocarbon receptor nuclear translocator-like 1 (BMAL1) and PERIOD
      2, is associated with a reduction in the activity/level of the deacetylase
      sirtuin 1 (SIRT1). Similarly, the levels of the nuclear receptor REV-ERBalpha and
      retinoic acid receptor-related orphan receptor alpha (ROR alpha), critical
      regulators of Bmal1 expression, are altered by environmental stresses. Molecular
      clock dysfunction is implicated in immune and inflammatory responses, DNA damage
      response, and cellular senescence. The molecular clock in the lung also regulates
      the timing of glucocorticoid sensitivity and phasic responsiveness to
      inflammation. Herein, we review our current understanding of clock-controlled
      cellular and molecular functions in the lungs, the impact of clock dysfunction in
      chronic airway disease, and the response of the pulmonary clock to different
      environmental perturbations. Furthermore, we discuss the evidence for candidate
      signaling pathways, such as the SIRT1-BMAL1-REV-ERBalpha axis, as novel targets
      for chronopharmacological management of chronic airway diseases. 

PMID- 25938936
TI  - Optimized diazo scaffold for protein esterification.
AB  - The O-alkylation of carboxylic acids with diazo compounds provides a means to
      esterify carboxylic acids in aqueous solution. A Hammett analysis of the
      reactivity of diazo compounds derived from phenylglycinamide revealed that the (p
      methylphenyl)glycinamide scaffold has an especially high reaction rate and
      ester/alcohol product ratio and esterifies protein carboxyl groups more
      efficiently than any known reagent. 

PMID- 25938937
TI  - Autoimmune Profiling Reveals Peroxiredoxin 6 as a Candidate Traumatic Brain
      Injury Biomarker.
AB  - Autoimmune profiling in rats revealed the antioxidant enzyme, peroxiredoxin 6
      (PRDX6), as a target for autoantibodies evoked in response to traumatic brain
      injury (TBI). Consistent with this proposal, immunohistochemical analysis of rat
      cerebral cortex demonstrated that PRDX6 is highly expressed in the perivascular
      space, presumably contained within astrocytic foot processes. Accordingly, an
      immunosorbent electrochemiluminescence assay was developed for investigating
      PRDX6 in human samples. PRDX6 was found to be measurable in human blood and
      highly expressed in human cerebral cortex and platelets. Circulating levels of
      PRDX6 were elevated fourfold over control values 4 to 24 h following mild-to
      moderate TBI. These findings suggest that PRDX6 may serve as a biomarker for TBI
      and that autoimmune profiling is a viable strategy for the discovery of novel TBI
      biomarkers.

PMID- 25938938
TI  - Probe-based Real-time PCR Approaches for Quantitative Measurement of microRNAs.
AB  - Probe-based quantitative PCR (qPCR) is a favoured method for measuring transcript
      abundance, since it is one of the most sensitive detection methods that provides
      an accurate and reproducible analysis. Probe-based chemistry offers the least
      background fluorescence as compared to other (dye-based) chemistries. Presently,
      there are several platforms available that use probe-based chemistry to
      quantitate transcript abundance. qPCR in a 96 well plate is the most routinely
      used method, however only a maximum of 96 samples or miRNAs can be tested in a
      single run. This is time-consuming and tedious if a large number of
      samples/miRNAs are to be analyzed. High-throughput probe-based platforms such as
      microfluidics (e.g. TaqMan Array Card) and nanofluidics arrays (e.g. OpenArray)
      offer ease to reproducibly and efficiently detect the abundance of multiple
      microRNAs in a large number of samples in a short time. Here, we demonstrate the
      experimental setup and protocol for miRNA quantitation from serum or plasma-EDTA
      samples, using probe-based chemistry and three different platforms (96 well
      plate, microfluidics and nanofluidics arrays) offering increasing levels of
      throughput. 

PMID- 25938939
TI  - Comparison of life cycle greenhouse gases from natural gas pathways for medium
      and heavy-duty vehicles.
AB  - The low-cost and abundant supply of shale gas in the United States has increased
      the interest in using natural gas for transportation. We compare the life cycle
      greenhouse gas (GHG) emissions from different natural gas pathways for medium and
      heavy-duty vehicles (MHDVs). For Class 8 tractor-trailers and refuse trucks, none
      of the natural gas pathways provide emissions reductions per unit of freight
      distance moved compared to diesel trucks. When compared to the petroleum-based
      fuels currently used in these vehicles, CNG and centrally produced LNG increase
      emissions by 0-3% and 2-13%, respectively, for Class 8 trucks. Battery electric
      vehicles (BEVs) powered with natural gas-produced electricity are the only fuel
      technology combination that achieves emission reductions for Class 8 transit
      buses (31% reduction compared to the petroleum-fueled vehicles). For non-Class 8
      trucks (pick-up trucks, parcel delivery trucks, and box trucks), BEVs reduce
      emissions significantly (31-40%) compared to their diesel or gasoline
      counterparts. CNG and propane achieve relatively smaller emissions reductions (0
      6% and 19%, respectively, compared to the petroleum-based fuels), while other
      natural gas pathways increase emissions for non-Class 8 MHDVs. While using
      natural gas to fuel electric vehicles could achieve large emission reductions for
      medium-duty trucks, the results suggest there are no great opportunities to
      achieve large emission reductions for Class 8 trucks through natural gas pathways
      with current technologies. There are strategies to reduce the carbon footprint of
      using natural gas for MHDVs, ranging from increasing vehicle fuel efficiency,
      reducing life cycle methane leakage rate, to achieving the same payloads and
      cargo volumes as conventional diesel trucks.

PMID- 25938940
TI  - Integrated fast assembly of free-standing lithium titanate/carbon
      nanotube/cellulose nanofiber hybrid network film as flexible paper-electrode for
      lithium-ion batteries.
AB  - A free-standing lithium titanate (Li4Ti5O12)/carbon nanotube/cellulose nanofiber
      hybrid network film is successfully assembled by using a pressure-controlled
      aqueous extrusion process, which is highly efficient and easily to scale up from
      the perspective of disposable and recyclable device production. This hybrid
      network film used as a lithium-ion battery (LIB) electrode has a dual-layer
      structure consisting of Li4Ti5O12/carbon nanotube/cellulose nanofiber composites
      (hereinafter referred to as LTO/CNT/CNF), and carbon nanotube/cellulose nanofiber
      composites (hereinafter referred to as CNT/CNF). In the heterogeneous fibrous
      network of the hybrid film, CNF serves simultaneously as building skeleton and a
      biosourced binder, which substitutes traditional toxic solvents and synthetic
      polymer binders. Of importance here is that the CNT/CNF layer is used as a
      lightweight current collector to replace traditional heavy metal foils, which
      therefore reduces the total mass of the electrode while keeping the same areal
      loading of active materials. The free-standing network film with high flexibility
      is easy to handle, and has extremely good conductivity, up to 15.0 S cm(-1). The
      flexible paper-electrode for LIBs shows very good high rate cycling performance,
      and the specific charge/discharge capacity values are up to 142 mAh g(-1) even at
      a current rate of 10 C. On the basis of the mild condition and fast assembly
      process, a CNF template fulfills multiple functions in the fabrication of paper
      electrode for LIBs, which would offer an ever increasing potential for high
      energy density, low cost, and environmentally friendly flexible electronics. 

PMID- 25938941
TI  - An in-cell fluorogenic Tag-probe system for protein dynamics imaging enabled by
      cell-penetrating peptides.
AB  - Fluorogenic probes are useful as molecular tools in chemical biology because they
      can overcome noise associated with background emission. Previously, using a
      leucine zipper assembly, we developed a fluorogenically active ZIP tag-probe
      pair. A probe peptide was designed as an alpha-helical peptide containing 4
      nitrobenzo-2-oxa-1,3-diazole, a solvatochromic fluorescent dye. Tag peptides were
      designed as antiparallel 2 alpha-helical peptides, and the tag and probe together
      form the 3 alpha-helical bundle structure of the leucine zipper. The use of the
      system was limited to membrane proteins or targets on the cellular surface
      because the probe peptide was not compatible with cell penetration. In this
      study, a challenge for the fluorescent imaging of proteins inside the cells was
      conducted by development of the ZIP tag-probe system as the second generation. To
      enable the cell penetration of the probe peptide, the addition of a cell
      penetrating peptide sequence was tested and a probe peptide with a C-terminal
      octa-arginine was shown to have high affinity for the tag peptide. In addition to
      attachment of a CPP structure, pretreatment of cells by 1-pyrenebutyrate enhanced
      distribution of the probe peptide into the cytosol. Observed colocalization of
      fluorescence of monomer Kusabira Orange and 4-nitrobenzo-2-oxa-1,3-diazole
      indicates our fluorogenic tag-probe system can be utilized with tagged proteins.
      Following stimulation by phorbol ester, the translocation of protein kinase C was
      tracked by the fluorescence of 4-nitrobenzo-2-oxa-1,3-diazole, suggesting the
      formation of the noncovalently assembled tag-probe pairing is maintained during
      the translocation, even when the concentration of the probe peptide is reduced to
      0.1 MUM. The results indicated that the dynamic change of the protein
      localization by chemical stimulations can be revealed by the ZIP tag-probe
      system. Above all, the system is simple to handle and highly compatible with
      virtually any protein inside the cells. 

PMID- 25938943
TI  - Mapping long-range promoter contacts in human cells with high-resolution capture
      Hi-C.
AB  - Transcriptional control in large genomes often requires looping interactions
      between distal DNA elements, such as enhancers and target promoters. Current
      chromosome conformation capture techniques do not offer sufficiently high
      resolution to interrogate these regulatory interactions on a genomic scale. Here
      we use Capture Hi-C (CHi-C), an adapted genome conformation assay, to examine the
      long-range interactions of almost 22,000 promoters in 2 human blood cell types.
      We identify over 1.6 million shared and cell type-restricted interactions
      spanning hundreds of kilobases between promoters and distal loci.
      Transcriptionally active genes contact enhancer-like elements, whereas
      transcriptionally inactive genes interact with previously uncharacterized
      elements marked by repressive features that may act as long-range silencers.
      Finally, we show that interacting loci are enriched for disease-associated SNPs,
      suggesting how distal mutations may disrupt the regulation of relevant genes.
      This study provides new insights and accessible tools to dissect the regulatory
      interactions that underlie normal and aberrant gene regulation. 

PMID- 25938942
TI  - NALP3 inflammasome upregulation and CASP1 cleavage of the glucocorticoid receptor
      cause glucocorticoid resistance in leukemia cells.
AB  - Glucocorticoids are universally used in the treatment of acute lymphoblastic
      leukemia (ALL), and resistance to glucocorticoids in leukemia cells confers poor
      prognosis. To elucidate mechanisms of glucocorticoid resistance, we determined
      the prednisolone sensitivity of primary leukemia cells from 444 patients newly
      diagnosed with ALL and found significantly higher expression of CASP1 (encoding
      caspase 1) and its activator NLRP3 in glucocorticoid-resistant leukemia cells,
      resulting from significantly lower somatic methylation of the CASP1 and NLRP3
      promoters. Overexpression of CASP1 resulted in cleavage of the glucocorticoid
      receptor, diminished the glucocorticoid-induced transcriptional response and
      increased glucocorticoid resistance. Knockdown or inhibition of CASP1
      significantly increased glucocorticoid receptor levels and mitigated
      glucocorticoid resistance in CASP1-overexpressing ALL. Our findings establish a
      new mechanism by which the NLRP3-CASP1 inflammasome modulates cellular levels of
      the glucocorticoid receptor and diminishes cell sensitivity to glucocorticoids.
      The broad impact on the glucocorticoid transcriptional response suggests that
      this mechanism could also modify glucocorticoid effects in other diseases. 

PMID- 25938944
TI  - A germline homozygous mutation in the base-excision repair gene NTHL1 causes
      adenomatous polyposis and colorectal cancer.
AB  - The genetic cause underlying the development of multiple colonic adenomas, the
      premalignant precursors of colorectal cancer (CRC), frequently remains unresolved
      in patients with adenomatous polyposis. Here we applied whole-exome sequencing to
      51 individuals with multiple colonic adenomas from 48 families. In seven affected
      individuals from three unrelated families, we identified a homozygous germline
      nonsense mutation in the base-excision repair (BER) gene NTHL1. This mutation was
      exclusively found in a heterozygous state in controls (minor allele frequency of
      0.0036; n = 2,329). All three families showed recessive inheritance of the
      adenomatous polyposis phenotype and progression to CRC in at least one member.
      All three affected women developed an endometrial malignancy or premalignancy.
      Genetic analysis of three carcinomas and five adenomas from different affected
      individuals showed a non-hypermutated profile enriched for cytosine-to-thymine
      transitions. We conclude that a homozygous loss-of-function germline mutation in
      the NTHL1 gene predisposes to a new subtype of BER-associated adenomatous
      polyposis and CRC. 

PMID- 25938945
TI  - Mutations in XPR1 cause primary familial brain calcification associated with
      altered phosphate export.
AB  - Primary familial brain calcification (PFBC) is a neurological disease
      characterized by calcium phosphate deposits in the basal ganglia and other brain
      regions and has thus far been associated with SLC20A2, PDGFB or PDGFRB mutations.
      We identified in multiple families with PFBC mutations in XPR1, a gene encoding a
      retroviral receptor with phosphate export function. These mutations alter
      phosphate export, implicating XPR1 and phosphate homeostasis in PFBC. 

PMID- 25938946
TI  - The draft genome of the grass carp (Ctenopharyngodon idellus) provides insights
      into its evolution and vegetarian adaptation.
AB  - The grass carp is an important farmed fish, accounting for ~16% of global
      freshwater aquaculture, and has a vegetarian diet. Here we report a 0.9-Gb draft
      genome of a gynogenetic female adult and a 1.07-Gb genome of a wild male adult.
      Genome annotation identified 27,263 protein-coding gene models in the female
      genome. A total of 114 scaffolds consisting of 573 Mb are anchored on 24 linkage
      groups. Divergence between grass carp and zebrafish is estimated to have occurred
      49-54 million years ago. We identify a chromosome fusion in grass carp relative
      to zebrafish and report frequent crossovers between the grass carp X and Y
      chromosomes. We find that transcriptional activation of the mevalonate pathway
      and steroid biosynthesis in liver is associated with the grass carp's adaptation
      from a carnivorous to an herbivorous diet. We believe that the grass carp genome
      could serve as an initial platform for breeding better-quality fish using a
      genomic approach. 

PMID- 25938947
TI  - Ruthenium(0) Catalyzed Endiyne-alpha-Ketol [4 + 2] Cycloaddition: Convergent
      Assembly of Type II Polyketide Substructures via C-C Bond Forming Transfer
      Hydrogenation.
AB  - Upon exposure of 3,4-benzannulated 1,5-diynes (benzo-endiynes) to alpha-ketols
      (alpha-hydroxyketones) in the presence of Ru(0) catalysts derived from Ru3(CO)12
      and RuPhos or CyJohnPhos, successive redox-triggered C-C coupling occurs to
      generate products of [4 + 2] cycloaddition. The proposed catalytic mechanism
      involves consecutive alkyne-carbonyl oxidative couplings to form transient
      oxaruthanacycles that suffer alpha-ketol mediated transfer hydrogenolysis. This
      process provides a new, convergent means of assembling Type II polyketide
      substructures. 

PMID- 25938948
TI  - Psychiatric symptoms in patients with sporadic Creutzfeldt-Jakob disease in
      Germany.
AB  - BACKGROUND: Psychiatric symptoms in sporadic Creutzfeldt-Jakob disease (sCJD) are
      still not sufficiently evaluated. AIM: To describe psychiatric symptoms in sCJD
      with respect to molecular subtype. METHOD: Patients in this retrospective study
      were classified according to established diagnostic criteria. 248 sCJD patients
      with known molecular subtype were recruited from January 1993 to December 2004
      and investigated. Psychiatric symptoms were defined according to Moller and
      colleagues and the AMDP system (Study Group for Methods and Documentation in
      Psychiatry) and were collected by direct examination by study physicians or
      extracted from medical documentation. Our data were compared with published data
      on variant CJD (vCJD). RESULTS: Psychiatric symptoms were common in sCJD patients
      (90%) and mostly found already at the disease onset (agitation in 64% of the
      patients, hallucinations in 45%, anxiety in 50%, depression in 37%). All
      psychiatric symptoms but illusions were found early in the disease course.
      Psychiatric symptoms in sCJD were less frequent than in vCJD. CONCLUSIONS: We
      provide the first detailed analysis of psychiatric symptoms in a large group of
      patients with sCJD with respect to differences concerning frequency and time
      point of occurrence of psychiatric symptoms between molecular subtypes. These
      data suggest that psychiatric symptoms occurring early in the disease course are
      common not only in vCJD but also in other CJD types.

PMID- 25938950
TI  - A Meta-ethnography: Skin-to-Skin Holding From the Caregiver's Perspective.
AB  - BACKGROUND: Although the benefits of skin-to-skin care (SSC) are well documented
      in the literature, practices in the clinical setting remain inconsistent.
      Although nurses' reported knowledge about SSC has improved, confusion still
      exists regarding safety and appropriateness. Existing qualitative literature
      primarily focuses on parents' experiences; yet it is crucial to describe the
      essence of professional caregivers' experiences to enhance facilitation and
      implementation of SSC. Most studies surrounding the caregiver's perspective and
      SSC have focused on barriers that impede implementation or examined the
      experience from the organizational perspective and general group experiences
      rather than individual personal experiences with SSC. PURPOSE: This meta
      ethnography integrated the findings from several discrete studies into a salient
      interpretative perspective, creating a relevant understanding of the process of
      SSC as a means of enhancing facilitation and implementation of SSC with
      hospitalized infants. METHODS: An ethnographic meta-synthesis of qualitative
      literature was completed. RESULTS: As a result of this synthesis, the caregivers'
      experiences were separated into themes to articulate the phenomena juxtaposed
      from the 8 original studies that influence facilitation of SSC for the parent
      infant dyad. Qualitative data analysis uncovered 4 overarching themes: (1)
      varying thresholds of getting started; (2) defining adequate resources; (3)
      navigating the demands and complexity of the infant; and (4) balancing parental
      readiness with infant needs. IMPLICATIONS FOR PRACTICE: This ethnographic meta
      synthesis confirms nurses have good intentions in supporting SSC practices, yet
      struggle to meet competing demands in their daily practice. IMPLICATIONS FOR
      RESEARCH: Innovative and practical translations of SSC are needed to normalize
      SSC as the daily standard for premature infants.

PMID- 25938949
TI  - Evaluation of Tumor-infiltrating Leukocyte Subsets in a Subcutaneous Tumor Model.
AB  - Specialized immune cells that infiltrate the tumor microenvironment regulate the
      growth and survival of neoplasia.  Malignant cells must elude or subvert anti
      tumor immune responses in order to survive and flourish. Tumors take advantage of
      a number of different mechanisms of immune "escape," including the recruitment of
      tolerogenic DC, immunosuppressive regulatory T cells (Tregs), and myeloid-derived
      suppressor cells (MDSC) that inhibit cytotoxic anti-tumor responses. Conversely,
      anti-tumor effector immune cells can slow the growth and expansion of
      malignancies: immunostimulatory dendritic cells, natural killer cells which
      harbor innate anti-tumor immunity, and cytotoxic T cells all can participate in
      tumor suppression. The balance between pro- and anti-tumor leukocytes ultimately
      determines the behavior and fate of transformed cells; a multitude of human
      clinical studies have borne this out. Thus, detailed analysis of leukocyte
      subsets within the tumor microenvironment has become increasingly important.
      Here, we describe a method for analyzing infiltrating leukocyte subsets present
      in the tumor microenvironment in a mouse tumor model. Mouse B16 melanoma tumor
      cells were inoculated subcutaneously in C57BL/6 mice. At a specified time, tumors
      and surrounding skin were resected en bloc and processed into single cell
      suspensions, which were then stained for multi-color flow cytometry. Using a
      variety of leukocyte subset markers, we were able to compare the relative
      percentages of infiltrating leukocyte subsets between control and chemerin
      expressing tumors. Investigators may use such a tool to study the immune presence
      in the tumor microenvironment and when combined with traditional caliper size
      measurements of tumor growth, will potentially allow them to elucidate the impact
      of changes in immune composition on tumor growth. Such a technique can be applied
      to any tumor model in which the tumor and its microenvironment can be resected
      and processed. 

PMID- 25938951
TI  - Got milk? Effects of early enteral feedings in patients with gastroschisis.
AB  - BACKGROUND: Initiating early enteral intake post-surgical gastroschisis repair
      may result in better patient outcomes. However, there is lack of evidence and
      consistency in clinical practice regarding the timing of initiation of feedings,
      and few studies have determined best practices for post-operative nutritional
      management. PURPOSE: To determine whether early nutritional management using a
      standardized advancement protocol improves outcomes for patients with
      gastroschisis. FINDINGS/RESULTS: A retrospective study was used, following the
      implementation of a new early enteral feeding protocol. Patients managed without
      the new protocol, from January 2007 through December 2009, formed the traditional
      feeding group, while those receiving post-protocol nutritional management, from
      January 2010 through December 2012, comprised the early enteral feeding group.
      The main outcome, measured by length of stay (LOS), and secondary outcomes,
      including incidence of sepsis, were evaluated; N = 32. There was a statistically
      significant difference in the scores for LOS (P = .022) and incidence of sepsis
      (P = .36). No correlation was found between the number of days to initial feeding
      and LOS (P = .732). However, there was a robust, positive correlation between the
      number of days to achieve full feedings and LOS (P < .001) IMPLICATIONS FOR
      PRACTICE: These findings support the benefit of early initiation of enteral
      feedings in reducing the incidence of sepsis. Furthermore, they suggest the time
      to achieve full enteral feedings, not necessarily the timing of initiation of
      feedings, significantly impacts LOS. IMPLICATIONS FOR RESEARCH: Consideration for
      future studies include incorporating strategies that combine early enteral
      feeding initiatives with interventions that allow for quicker onset of full
      enteral intake.

PMID- 25938952
TI  - Topical Nystatin for the Prevention of Catheter-Associated Candidiasis in ELBW
      Infants.
AB  - BACKGROUND: Catheter-associated Candida bloodstream infections are a common and
      serious problem in the neonatal intensive care unit (NICU). Several prophylactic
      regimens have been developed including oral administration of nonabsorbable
      antifungals and intravenous infusions. No reports to date have employed a topical
      regimen. PURPOSE: To evaluate the effectiveness of topical nystatin cream in
      preventing catheter-associated Candida sepsis. METHODS: A retrospective
      descriptive design was used to determine the incidence of Candida sepsis in
      extremely low-birth weight (ELBW, <1000 g at birth) infants who were treated with
      topical nystatin cream for Candida bloodstream infection prophylaxis between
      January 1, 2000, and December 31, 2010. The electronic medical records of study
      infants were reviewed to establish the incidence of Candida sepsis. RESULTS: A
      total of 464 ELBW infants were admitted to the NICU during the study period.
      Three infants (0.65%) developed Candida sepsis. IMPLICATIONS FOR PRACTICE: These
      data demonstrate that a topical nystatin cream protocol is associated with a very
      low rate of Candida sepsis in ELBW infants with central catheters. The use of
      this protocol may contribute to a decrease in the morbidity and mortality rate
      associated with catheter-associated Candida infections in ELBW infants.
      IMPLICATIONS FOR RESEARCH: Before generalizations can be made as to the safety
      and efficacy of this protocol as compared to enteral and parenteral prophylactic
      treatments and in other institutions, large multicenter randomized controlled
      trials are required.

PMID- 25938953
TI  - Microsecond protein folding events revealed by time-resolved fluorescence
      resonance energy transfer in a microfluidic mixer.
AB  - We demonstrate the combination of the time-resolved fluorescence resonance energy
      transfer (tr-FRET) measurement and the ultrarapid hydrodynamic focusing
      microfluidic mixer. The combined technique is capable of probing the
      intermolecular distance change with temporal resolution at microsecond level and
      structural resolution at Angstrom level, and the use of two-photon excitation
      enables a broader exploration of FRET with spectrum from near-ultraviolet to
      visible wavelength. As a proof of principle, we used the coupled microfluidic
      laminar flow and time-resolved two-photon excitation microscopy to investigate
      the early folding states of Cytochrome c (cyt c) by monitoring the distance
      between the tryptophan (Trp-59)-heme donor-acceptor (D-A) pair. The
      transformation of folding states of cyt c in the early 500 MUs of refolding was
      revealed on the microsecond time scale. For the first time, we clearly resolved
      the early transient state of cyt c, which is populated within the dead time of
      the mixer (<10 MUs) and has a characteristic Trp-59-heme distance of ~31 A. We
      believe this tool can find more applications in studying the early stages of
      biological processes with FRET as the probe. 

PMID- 25938954
TI  - Post-extinction selective persistence of large dendritic spines in fear remodeled
      circuits may serve to reactivate fear.
AB  - Memory formation associates with changes in strength and efficacy of existing
      synapses and with the formation of new synapses. Dendritic spines, the membranous
      protrusions from neuron dendrites that host the majority of excitatory synapses,
      are the anatomical sites where neuronal activity reshapes brain networks in
      response to stimuli. Mounting evidence indicates that structural changes in fear
      remodeled circuits undergo partially erasure following extinction, suggesting
      that the changes that persist may serve to reactivate memory. Here we review data
      showing how brain circuits are remodeled at the time fear memory is formed and
      extinguished, with a special focus put on the post-extinction persistence of
      spine enlargement in relation to memory reactivation. 

PMID- 25938955
TI  - Facial Feminization Surgery: The Forehead. Surgical Techniques and Analysis of
      Results.

PMID- 25938957
TI  - Medial Thigh Lift in the Massive Weight Loss Population: Outcomes and
      Complications.

PMID- 25938958
TI  - Emerging Paradigms in Perioperative Management for Microsurgical Free Tissue
      Transfer: Review of the Literature and Evidence-Based Guidelines.

PMID- 25938959
TI  - The Sacred Heart Bilobed Flap: A Simple Method for Closing Small Scalp Defects.

PMID- 25938960
TI  - The U-Shaped Tensor Fasciae Latae Musculocutaneous Flap for Coverage of
      Trochanteric Defects: Simplified Design to Minimize Donor-Site Morbidity.

PMID- 25938961
TI  - Suction Drain-Assisted Split-Thickness Skin Grafting: A Simple Procedure to
      Improve Skin Graft Take.

PMID- 25938962
TI  - An Oncoplastic Approach to Reconstruct Upper Pole Partial Mastectomy Defects in
      Minimally Ptotic and Average Size Breasts.

PMID- 25938963
TI  - Biarylmethane and Fused Heterocyclic Arene Synthesis via in Situ Generated o-
      and/or p-Naphthoquinone Methides.
AB  - o- and/or p-naphthoquinone methides (NQMs) can be selectively prepared by the
      ring opening of 1-(siloxymethyl)-1,4-epoxy-1,4-dihydronaphthalene derivatives
      based on a substituent effect at the 4 position of the substrates. The 4-alkyl-
      or silyl-substituted 1-(siloxymethyl)-1,4-epoxy-1,4-dihydronaphthalene was
      transformed to o-NQM (1-naphthoquinone-2-methide), which underwent Friedel-Crafts
      1,4-addition of the alpha,beta-unsaturated carbonyl moiety to provide the 2
      benzyl-1-naphthol as the biarylmethane and [4 + 2]-cycloaddition with a
      dienophile to give the fused heterocyclic arene. Meanwhile, the 4-unsubstituted 1
      (siloxymethyl)-1,4-epoxy-1,4-dihydronaphthalene could be converted to the
      corresponding 4-benzyl-1-naphthol by the Friedel-Crafts 1,6-addition of p-NQM (1
      naphthoquinone-4-methide) generated by the site-selective ring opening of the 1,4
      epoxy moiety. Furthermore, the 4-(siloxymethyl)-(1,4-bis(siloxymethyl))-1,4-epoxy
      1,4-dihydronaphthalene was transformed into a 2,4-bisbenzyl-1-naphthol or
      pentacyclic derivative via both the o- and p-NQM intermediates. 

PMID- 25938964
TI  - The miRNA Transcriptome Directly Reflects the Physiological and Biochemical
      Differences between Red, White, and Intermediate Muscle Fiber Types.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that can regulate their target genes
      at the post-transcriptional level. Skeletal muscle comprises different fiber
      types that can be broadly classified as red, intermediate, and white. Recently, a
      set of miRNAs was found expressed in a fiber type-specific manner in red and
      white fiber types. However, an in-depth analysis of the miRNA transcriptome
      differences between all three fiber types has not been undertaken. Herein, we
      collected 15 porcine skeletal muscles from different anatomical locations, which
      were then clearly divided into red, white, and intermediate fiber type based on
      the ratios of myosin heavy chain isoforms. We further illustrated that three
      muscles, which typically represented each muscle fiber type (i.e., red: peroneal
      longus (PL), intermediate: psoas major muscle (PMM), white: longissimus dorsi
      muscle (LDM)), have distinct metabolic patterns of mitochondrial and glycolytic
      enzyme levels. Furthermore, we constructed small RNA libraries for PL, PMM, and
      LDM using a deep sequencing approach. Results showed that the differentially
      expressed miRNAs were mainly enriched in PL and played a vital role in myogenesis
      and energy metabolism. Overall, this comprehensive analysis will contribute to a
      better understanding of the miRNA regulatory mechanism that achieves the
      phenotypic diversity of skeletal muscles. 

PMID- 25938967
TI  - New Coumarin Derivatives and Other Constituents from the Stem Bark of Zanthoxylum
      avicennae: Effects on Neutrophil Pro-Inflammatory Responses.
AB  - Three new coumarin derivatives, 8-formylalloxanthoxyletin (1), avicennone (2),
      and (Z)-avicennone (3), have been isolated from the stem bark of Zanthoxylum
      avicennae (Z. avicennae), together with 15 known compounds (4-18). The structures
      of these new compounds were determined through spectroscopic and MS analyses.
      Compounds 1, 4, 9, 12, and 15 exhibited inhibition (half maximal inhibitory
      concentration (IC50) values <=7.65 ug/mL) of superoxide anion generation by human
      neutrophils in response to formyl-l-methionyl-l-leucyl-l
      phenylalanine/cytochalasin B (fMLP/CB). Compounds 1, 2, 4, 8 and 9 inhibited
      fMLP/CB-induced elastase release with IC50 values <=8.17 ug/mL. This
      investigation reveals bioactive isolates (especially 1, 2, 4, 8, 9, 12 and 15)
      could be further developed as potential candidates for the treatment or
      prevention of various inflammatory diseases.

PMID- 25938965
TI  - Structural basis for carbapenem-hydrolyzing mechanisms of carbapenemases
      conferring antibiotic resistance.
AB  - Carbapenems (imipenem, meropenem, biapenem, ertapenem, and doripenem) are beta
      lactam antimicrobial agents. Because carbapenems have the broadest spectra among
      all beta-lactams and are primarily used to treat infections by multi-resistant
      Gram-negative bacteria, the emergence and spread of carbapenemases became a major
      public health concern. Carbapenemases are the most versatile family of beta
      lactamases that are able to hydrolyze carbapenems and many other beta-lactams.
      According to the dependency of divalent cations for enzyme activation,
      carbapenemases can be divided into metallo-carbapenemases (zinc-dependent class
      B) and non-metallo-carbapenemases (zinc-independent classes A, C, and D). Many
      studies have provided various carbapenemase structures. Here we present a
      comprehensive and systematic review of three-dimensional structures of
      carbapenemase-carbapenem complexes as well as those of carbapenemases. We update
      recent studies in understanding the enzymatic mechanism of each class of
      carbapenemase, and summarize structural insights about regions and residues that
      are important in acquiring the carbapenemase activity. 

PMID- 25938968
TI  - De Novo Transcriptome Sequencing of Low Temperature-Treated Phlox subulata and
      Analysis of the Genes Involved in Cold Stress.
AB  - Phlox subulata, a perennial herbaceous flower, can survive during the winter of
      northeast China, where the temperature can drop to -30  degrees C, suggesting
      that P. subulata is an ideal model for studying the molecular mechanisms of cold
      acclimation in plants. However, little is known about the gene expression profile
      of P. subulata under cold stress. Here, we examined changes in cold stress
      related genes in P. subulata. We sequenced three cold-treated (CT) and control
      (CK) samples of P. subulata. After de novo assembly and quantitative assessment
      of the obtained reads, 99,174 unigenes were generated. Based on similarity
      searches with known proteins in public protein databases, 59,994 unigenes were
      functionally annotated. Among all differentially expressed genes (DEGs), 8302,
      10,638 and 11,021 up-regulated genes and 9898, 17,876, and 12,358 down-regulated
      genes were identified after treatment at 4, 0, and -10  degrees C, respectively.
      Furthermore, 3417 up-regulated unigenes were expressed only in CT samples. Twenty
      major cold-related genes, including transcription factors, antioxidant enzymes,
      osmoregulation proteins, and Ca2+ and ABA signaling components, were identified,
      and their expression levels were estimated. Overall, this is the first
      transcriptome sequencing of this plant species under cold stress. Studies of DEGs
      involved in cold-related metabolic pathways may facilitate the discovery of cold
      resistance genes.

PMID- 25938966
TI  - MicroRNA Expression Profile of Neural Progenitor-Like Cells Derived from Rat Bone
      Marrow Mesenchymal Stem Cells under the Influence of IGF-1, bFGF and EGF.
AB  - Insulin-like growth factor 1 (IGF-1) enhances cellular proliferation and reduces
      apoptosis during the early differentiation of bone marrow derived mesenchymal
      stem cells (BMSCs) into neural progenitor-like cells (NPCs) in the presence of
      epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). BMSCs
      were differentiated in three groups of growth factors: (A) EGF + bFGF, (B) EGF +
      bFGF + IGF-1, and (C) without growth factor. To unravel the molecular mechanisms
      of the NPCs derivation, microarray analysis using GeneChip miRNA arrays was
      performed. The profiles were compared among the groups. Annotated microRNA
      fingerprints (GSE60060) delineated 46 microRNAs temporally up-regulated or down
      regulated compared to group C. The expressions of selected microRNAs were
      validated by real-time PCR. Among the 46 microRNAs, 30 were consistently
      expressed for minimum of two consecutive time intervals. In Group B, only miR-496
      was up-regulated and 12 microRNAs, including the let-7 family, miR-1224, miR-125a
      3p, miR-214, miR-22, miR-320, miR-708, and miR-93, were down-regulated.
      Bioinformatics analysis reveals that some of these microRNAs (miR-22, miR-214,
      miR-125a-3p, miR-320 and let-7 family) are associated with reduction of
      apoptosis. Here, we summarize the roles of key microRNAs associated with IGF-1 in
      the differentiation of BMSCs into NPCs. These findings may provide clues to
      further our understanding of the mechanisms and roles of microRNAs as key
      regulators of BMSC-derived NPC maintenance.

PMID- 25938969
TI  - Ultrasound imaging for risk assessment in atherosclerosis.
AB  - Atherosclerosis and its consequences like acute myocardial infarction or stroke
      are highly prevalent in western countries, and the incidence of atherosclerosis
      is rapidly rising in developing countries. Atherosclerosis is a disease that
      progresses silently over several decades before it results in the aforementioned
      clinical consequences. Therefore, there is a clinical need for imaging methods to
      detect the early stages of atherosclerosis and to better risk stratify patients.
      In this review, we will discuss how ultrasound imaging can contribute to the
      detection and risk stratification of atherosclerosis by (a) detecting advanced
      and early plaques; (b) evaluating the biomechanical consequences of
      atherosclerosis in the vessel wall; 

PMID- 25938970
TI  - Clouded Issues for PHACTR1.
AB  - I have read with interest the recent paper by Han and coworkers on the putative
      effects of a PHACTR1 variant in the context of coronary artery disease. The
      authors conclude to a significant risk-enhancing role of rs12526453 on the
      grounds of 19 earlier case-control studies.

PMID- 25938971
TI  - Changing the face of kynurenines and neurotoxicity: therapeutic considerations.
AB  - Kynurenines are the products of tryptophan metabolism. Among them, kynurenine and
      kynurenic acid are generally thought to have neuroprotective properties, while 3
      hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid are considered
      neurotoxic. They participate in immunoregulation and inflammation and possess pro
      or anti-excitotoxic properties, and their involvement in oxidative stress has
      also been suggested. Consequently, it is not surprising that kynurenines have
      been closely related to neurodegenerative diseases, such as Alzheimer's disease,
      Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and
      multiple sclerosis. More information about the less-known metabolites, picolinic
      and cinnabarinic acid, evaluation of new receptorial targets, such as aryl
      hydrocarbon receptors, and intensive research on the field of the
      immunomodulatory function of kynurenines delineated the high importance of this
      pathway in general homeostasis. Emerging knowledge about the kynurenine pathway
      provides new target points for the development of therapeutical solutions against
      neurodegenerative diseases. 

PMID- 25938972
TI  - Association between PDCD1 Gene Polymorphisms and Risk of Systemic Lupus
      Erythematosus in Three Main Ethnic Groups of the Malaysian Population.
AB  - The programmed cell death 1 (PDCD1) gene encodes for the PD-1 (programmed death
      1) molecule, which negatively regulates self-reactive T- and B-cells in the
      maintenance of peripheral tolerance. A previous report had shown the development
      of lupus-like phenotypes in PD-1-deficient C57BL/6 mice, was suggestive to the
      role of PDCD1 in predisposing to systemic lupus erythematosus (SLE). Hence, we
      aimed to investigate the association between PDCD1 and SLE susceptibility in the
      Malaysian population. A TaqMan-based real-time PCR was employed to screen for
      PD1.1, PD1.3, PD1.5 and PD1.6 in both SLE and healthy control groups of 200
      samples each. The observed frequency for PD1.5C/C genotype was significantly
      higher in Indian SLE patients and Malay controls (p < 0.01). On the other hand,
      the PD1.5C/T genotype might predispose the Malays to SLE, but confer a protective
      effect among the Indians (p < 0.01). The PD1.1, PD1.3 and PD1.6 were, however,
      not correlated to genetic predisposition of SLE in our Malaysian population. In
      conclusion, PD1.5 variant was significantly associated to SLE susceptibility in
      our Malaysian cohort. Our failure in replicating the association between other
      investigated PDCD1 variants and risk of getting SLE might due to ethnic and
      geographic variations in the distribution of these genetic variants. 

PMID- 25938974
TI  - Choice deferral can arise from absolute evaluations or relative comparisons.
AB  - When choosing among several options, people may defer choice for either of 2
      reasons: because none of the options is good enough or because there is
      uncertainty regarding which is the best. These reasons form the basis of the 2
      stage, 2-threshold (2S2T) framework, which posits that a different kind of
      processing corresponds to these 2 reasons for choice deferral: absolute
      evaluations and relative comparisons, respectively. Three experiments are
      reported in which each type of processing was triggered in different conditions
      either via different payoff structures or different degrees of attribute
      knowledge. The effects of the 3 main independent variables (the size of the
      choice set, the utility of the best option, and the number of competitive
      options) differed depending on the payoff structure or attribute knowledge
      conditions in ways predicted by the 2S2T framework. Implications for consumer
      decision making, marketing, and eyewitness identification are discussed.

PMID- 25938973
TI  - Microfluidic impedance flow cytometry enabling high-throughput single-cell
      electrical property characterization.
AB  - This article reviews recent developments in microfluidic impedance flow cytometry
      for high-throughput electrical property characterization of single cells. Four
      major perspectives of microfluidic impedance flow cytometry for single-cell
      characterization are included in this review: (1) early developments of
      microfluidic impedance flow cytometry for single-cell electrical property
      characterization; (2) microfluidic impedance flow cytometry with enhanced
      sensitivity; (3) microfluidic impedance and optical flow cytometry for single
      cell analysis and (4) integrated point of care system based on microfluidic
      impedance flow cytometry. We examine the advantages and limitations of each
      technique and discuss future research opportunities from the perspectives of both
      technical innovation and clinical applications. 

PMID- 25938975
TI  - Improving risk understanding across ability levels: Encouraging active processing
      with dynamic icon arrays.
AB  - Icon arrays have been found to improve risk understanding and reduce judgment
      biases across a wide range of studies. Unfortunately, individuals with low graph
      literacy experience only limited benefits from such displays. To enhance the
      efficacy and reach of these decision aids, the authors developed and tested 3
      types of dynamic design features--that is, computerized display features that
      unfold over time. Specifically, the authors manipulated the sequential
      presentation of the different elements of icon arrays, the presence of
      explanatory labels indicating what was depicted in the different regions of the
      arrays, and the use of a reflective question followed by accuracy feedback. The
      first 2 features were designed to promote specific cognitive processes involved
      in graph comprehension, whereas the 3rd feature was designed to promote a more
      active, elaborative processing of risk information. Explanatory labels were
      effective in improving risk understanding among less graph-literate participants,
      whereas reflective questions resulted in large and robust performance benefits
      among participants with both low and high graph literacy. Theoretical and
      prescriptive implications are discussed. (PsycINFO Database Record

PMID- 25938976
TI  - A theoretical and experimental approach for correlating nanoparticle structure
      and electrocatalytic activity.
AB  - The objective of the research described in this Account is the development of
      high-throughput computational-based screening methods for discovery of catalyst
      candidates and subsequent experimental validation using appropriate catalytic
      nanoparticles. Dendrimer-encapsulated nanoparticles (DENs), which are well
      defined 1-2 nm diameter metal nanoparticles, fulfill the role of model
      electrocatalysts. Effective comparison of theory and experiment requires that the
      theoretical and experimental models map onto one another perfectly. We use novel
      synthetic methods, advanced characterization techniques, and density functional
      theory (DFT) calculations to approach this ideal. For example, well-defined
      core@shell DENs can be synthesized by electrochemical underpotential deposition
      (UPD), and the observed deposition potentials can be compared to those calculated
      by DFT. Theory is also used to learn more about structure than can be determined
      by analytical characterization alone. For example, density functional theory
      molecular dynamics (DFT-MD) was used to show that the core@shell configuration of
      Au@Pt DENs undergoes a surface reconstruction that dramatically affects its
      electrocatalytic properties. A separate Pd@Pt DENs study also revealed
      reorganization, in this case a core-shell inversion to a Pt@Pd structure.
      Understanding these types of structural changes is critical to building
      correlations between structure and catalytic function. Indeed, the second
      principal focus of the work described here is correlating structure and catalytic
      function through the combined use of theory and experiment. For example, the
      Au@Pt DENs system described earlier is used for the oxygen reduction reaction
      (ORR) as well as for the electro-oxidation of formic acid. The surface
      reorganization predicted by theory enhances our understanding of the catalytic
      measurements. In the case of formic acid oxidation, the deformed nanoparticle
      structure leads to reduced CO binding energy and therefore improved oxidation
      activity. The final catalytic study we present is an instance of theory correctly
      predicting (in advance of the experiments) the structure of an effective DEN
      electrocatalyst. Specifically, DFT was used to determine the optimal composition
      of the alloy-core in AuPd@Pt DENs for the ORR. This prediction was subsequently
      confirmed experimentally. This study highlights the major theme of our research:
      the progression of using theory to rationalize experimental results to the more
      advanced goal of using theory to predict catalyst function a priori. We still
      have a long way to go before theory will be the principal means of catalyst
      discovery, but this Account begins to shed some light on the path that may lead
      in that direction. 

PMID- 25938977
TI  - Effect of ebosin on modulating interleukin-1beta-induced inflammatory responses
      in rat fibroblast-like synoviocytes.
AB  - The interleukin-1beta-mitogen-activated protein kinase (MAPK) and NF-kappaB
      signaling pathways are involved in the pathogenesis of rheumatoid arthritis.
      Ebosin, a novel exopolysaccharide (EPS), exhibits anti-inflammatory activity in
      rat collagen-induced arthritis by suppressing the production of tumor necrosis
      factor-alpha, interleukin-6 and interleukin-1beta. The aim of the present study
      was to assess the effects of ebosin on NF-kappaB and MAPK signaling pathways
      mediated through interleukin-1beta in rat fibroblast-like synoviocytes (FLSs).
      Western blotting showed decreased production of phosphorylated p38, JNK1, JNK2,
      IKKalpha, IKKbeta and IkappaB in the cytoplasm and NF-kappaB in the nucleus upon
      ebosin treatment. The DNA-binding activity of NF-kappaB in the cell nucleus was
      also inhibited by ebosin treatment, as demonstrated using an electrophoresis
      mobility gel shift assay. Analysis of the results of the immunofluorescence assay
      also showed a reduced amount of NF-kappaB in the nucleus of cells affected by
      ebosin. These results provided evidence for the effects of ebosin on both
      interleukin-1beta-mediated MAPK and NF-kappaB signaling pathways in rat FLSs. In
      addition, enzyme-linked immunosorbent assay demonstrated that ebosin reduces the
      levels of matrix metalloproteinases MMP-1 and MMP-3 and the chemokines,
      interleukin-8 and RANTES. Thus, the results of the present study provide further
      evidence for understanding the medicinal activity of ebosin at a molecular level,
      therefore nominating this EPS as a potential therapeutic candidate for the
      treatment of rheumatic arthritis.Cellular & Molecular Immunology advance online
      publication, 4 May 2015; doi:10.1038/cmi.2015.36.

PMID- 25938978
TI  - Immunomodulatory properties of silver nanoparticles contribute to anticancer
      strategy for murine fibrosarcoma.
AB  - The use of nanotechnology in nanoparticle-based cancer therapeutics is gaining
      impetus due to the unique biophysical properties of nanoparticles at the quantum
      level. Silver nanoparticles (AgNPs) have been reported as one type of potent
      therapeutic nanoparticles. The present study is aimed to determine the effect of
      AgNPs in arresting the growth of a murine fibrosarcoma by a reductive mechanism.
      Initially, a bioavailability study showed that mouse serum albumin (MSA)-coated
      AgNPs have enhanced uptake; therefore, toxicity studies of AgNP-MSA at 10
      different doses (1-10 mg/kg b.w.) were performed in LACA mice by measuring the
      complete blood count, lipid profile and histological parameters. The complete
      blood count, lipid profile and histological parameter results showed that the
      doses from 2 to 8 mg (IC50: 6.15 mg/kg b.w.) sequentially increased the count of
      leukocytes, lymphocytes and granulocytes, whereas the 9- and 10-mg doses showed
      conclusive toxicity. In an antitumor study, the incidence and size of
      fibrosarcoma were reduced or delayed when murine fibrosarcoma groups were treated
      by AgNP-MSA. Transmission electron micrographs showed that considerable uptake of
      AgNP-MSA by the sentinel immune cells associated with tumor tissue and a
      morphologically buckled structure of the immune cells containing AgNP-MSA.
      Because the toxicity studies revealed a relationship between AgNPs and immune
      function, the protumorigenic cytokines TNF-alpha, IL-6 and IL-1beta were also
      assayed in AgNP-MSA-treated and non-treated fibrosarcoma groups, and these
      cytokines were found to be downregulated after treatment with AgNP-MSA. 

PMID- 25938979
TI  - The influence of duckweed species diversity on ecophysiological tolerance to
      copper exposure.
AB  - In excess, copper is toxic to plants. In the plants, Landoltia punctata and Lemna
      minor grown in mixed and monoculture, the effects of exposure to varying
      concentrations of copper (0.01, 0.1, 0.5 and 1mgL(-1) Cu) for seven days were
      assessed by measuring changes in the chlorophyll, protein and malondialdehyde
      (MDA) content, catalase (CAT), superoxide dismutase (SOD) and ascorbate
      peroxidase (APX) activity. According to results, Cu levels in plants increased
      with increasing Cu concentration. The level of photosynthetic pigments and crude
      proteins decreased only upon exposure to high Cu concentrations. However, the
      starch and malondialdehyde (MDA) content increased. These results suggested a
      stress alleviation that was possibly the result of antioxidants such as CAT and
      SOD, the activities of which increased with increasing Cu levels. APX activity
      increased in L. punctata, but decreased in L. minor, under monoculture or mixed
      culture conditions. In addition, the duckweed in mixed culture exhibited
      increased antioxidant enzyme activities which provide increased resistance to
      copper in moderate copper concentrations. As the copper concentration increased,
      the duckweed in the mixed culture limited the uptake of copper to avoid toxicity.

PMID- 25938980
TI  - Lysosomal responses to heat-shock of seasonal temperature extremes in Cd-exposed
      mussels.
AB  - The present study was aimed at determining the effect of temperature extremes on
      lysosomal biomarkers in mussels exposed to a model toxic pollutant (Cd) at
      different seasons. For this purpose, temperature was elevated 10 degrees C (from
      12 degrees C to 22 degrees C in winter and from 18 degrees C to 28 degrees C in
      summer) for a period of 6h (heat-shock) in control and Cd-exposed mussels, and
      then returned back to initial one. Lysosomal membrane stability and lysosomal
      structural changes in digestive gland were investigated. In winter, heat-shock
      reduced the labilisation period (LP) of the lysosomal membrane, especially in Cd
      exposed mussels, and provoked transient lysosomal enlargement. LP values
      recovered after the heat-shock cessation but lysosomal enlargement prevailed in
      both experimental groups. In summer, heat-shock induced remarkable reduction in
      LP and lysosomal enlargement (more markedly in Cd-exposed mussels), which
      recovered within 3 days. Besides, whilst heat-shock effects on LP were
      practically identical for Cd-exposed mussels in winter and summer, the effects
      were longer-lasting in summer than in winter for control mussels. Thus, lysosomal
      responsiveness after heat-shock was higher in summer than in winter but recovery
      was faster as well, and therefore the consequences of the heat shock seem to be
      more decisive in winter. In contrast, inter-season differences were attenuated in
      the presence of Cd. Consequently, mussels seem to be better prepared in summer
      than in winter to stand short periods of abrupt temperature change; this is,
      however, compromised when mussels are exposed to pollutants such as Cd. 

PMID- 25938981
TI  - What steps do we need to take to improve diagnosis of tuberculosis in children?
AB  - Tuberculosis still represents a big global public health challenge. The diagnosis
      of tuberculosis and the differentiation between active and latent tuberculosis
      remain difficult, particularly in childhood, because of the lack of a gold
      standard test for diagnosis. In the last decade, novel diagnostic assays have
      been developed. Among immunologic tests, new assays based on the measurement of
      different cytokines released by specific T cells in response to Mycobacterium
      tuberculosis antigens, other than INF-gamma, have been investigated. Promising
      results rely on nucleic acid amplification techniques, also able to detect drugs
      resistance. Innovative research fields studied the modifications of CD27
      expression in T cells as well as different host gene expression in response to M.
      tuberculosis. Further studies are needed to assess the diagnostic value and the
      accuracy of these new assays. 

PMID- 25938984
TI  - A Simple Approach to Reducing Inappropriate Use of Central Venous Catheters.

PMID- 25938982
TI  - Essential Role of the ESX-5 Secretion System in Outer Membrane Permeability of
      Pathogenic Mycobacteria.
AB  - Mycobacteria possess different type VII secretion (T7S) systems to secrete
      proteins across their unusual cell envelope. One of these systems, ESX-5, is only
      present in slow-growing mycobacteria and responsible for the secretion of
      multiple substrates. However, the role of ESX-5 substrates in growth and/or
      virulence is largely unknown. In this study, we show that esx-5 is essential for
      growth of both Mycobacterium marinum and Mycobacterium bovis. Remarkably, this
      essentiality can be rescued by increasing the permeability of the outer membrane,
      either by altering its lipid composition or by the introduction of the
      heterologous porin MspA. Mutagenesis of the first nucleotide-binding domain of
      the membrane ATPase EccC5 prevented both ESX-5-dependent secretion and bacterial
      growth, but did not affect ESX-5 complex assembly. This suggests that the
      rescuing effect is not due to pores formed by the ESX-5 membrane complex, but
      caused by ESX-5 activity. Subsequent proteomic analysis to identify crucial ESX-5
      substrates confirmed that all detectable PE and PPE proteins in the cell surface
      and cell envelope fractions were routed through ESX-5. Additionally, saturated
      transposon-directed insertion-site sequencing (TraDIS) was applied to both wild
      type M. marinum cells and cells expressing mspA to identify genes that are not
      essential anymore in the presence of MspA. This analysis confirmed the importance
      of esx-5, but we could not identify essential ESX-5 substrates, indicating that
      multiple of these substrates are together responsible for the essentiality.
      Finally, examination of phenotypes on defined carbon sources revealed that an esx
      5 mutant is strongly impaired in the uptake and utilization of hydrophobic carbon
      sources. Based on these data, we propose a model in which the ESX-5 system is
      responsible for the transport of cell envelope proteins that are required for
      nutrient uptake. These proteins might in this way compensate for the lack of MspA
      like porins in slow-growing mycobacteria. 

PMID- 25938983
TI  - A community-based intervention increases physical activity and reduces obesity in
      school-age children in North Carolina.
AB  - BACKGROUND: Community-based interventions are promising approaches to obesity
      prevention, but few studies have prospectively evaluated them. The aim of this
      study was to evaluate a natural experiment-a community intervention designed to
      promote active living and decrease obesity within a small southern town. METHODS:
      In 2011, community leaders implemented the Mebane on the Move intervention-a
      community-wide effort to promote physical activity (PA) and decrease obesity
      among residents of Mebane, North Carolina. We measured child PA and BMI before
      and after the intervention, using a nearby town not implementing an intervention
      as the comparison. In total, we assessed 64 children from Mebane and 40 from the
      comparison community 6 months before, as well as 34 and 18 children 6 months
      after the intervention. We assessed PA with accelerometers worn for 7 days and
      calculated BMI z-scores using children's height and weight. We conducted
      multivariable linear regressions examining pre- to postintervention change in
      minutes of PA and BMI z-score, adjusting for confounders. RESULTS: At follow-up,
      children in Mebane modestly increased their moderate-to-vigorous PA (1.3 minutes
      per hour; 95% confidence interval (CI): 0.2, 2.3; p=0.03) and vigorous activity
      (0.8 minutes per hour; 95% CI: 0.1, 1.5; p=0.04) more than comparison children.
      In intervention children, BMI z-scores decreased 0.5 units (kg/m(2); 95% CI: 
      0.9, -0.02; p=0.045), compared to children in the comparison community.
      CONCLUSIONS: We observed positive effects on PA level and weight status of
      children in Mebane, despite high rates of attrition, suggesting that the
      community-based intervention may have been successful.

PMID- 25938985
TI  - Viral-mediated Labeling and Transplantation of Medial Ganglionic Eminence (MGE)
      Cells for In Vivo Studies.
AB  - GABAergic cortical interneurons, derived from the embryonic medial and caudal
      ganglionic eminences (MGE and CGE), are functionally and morphologically diverse.
      Inroads have been made in understanding the roles of distinct cortical
      interneuron subgroups, however, there are still many mechanisms to be worked out
      that may contribute to the development and maturation of different types of
      GABAergic cells. Moreover, altered GABAergic signaling may contribute to
      phenotypes of autism, schizophrenia and epilepsy. Specific Cre-driver lines have
      begun to parcel out the functions of unique interneuron subgroups. Despite the
      advances in mouse models, it is often difficult to efficiently study GABAergic
      cortical interneuron progenitors with molecular approaches in vivo. One important
      technique used to study the cell autonomous programming of these cells is
      transplantation of MGE cells into host cortices. These transplanted cells migrate
      extensively, differentiate, and functionally integrate. In addition, MGE cells
      can be efficiently transduced with lentivirus immediately prior to
      transplantation, allowing for a multitude of molecular approaches. Here we detail
      a protocol to efficiently transduce MGE cells before transplantation for in vivo
      analysis, using available Cre-driver lines and Cre-dependent expression vectors.
      This approach is advantageous because it combines precise genetic manipulation
      with the ability of these cells to disperse after transplantation, permitting
      greater cell-type specific resolution in vivo. 

PMID- 25938986
TI  - Design, synthesis and antibacterial activity of cinnamaldehyde derivatives as
      inhibitors of the bacterial cell division protein FtsZ.
AB  - In an attempt to discover potential antibacterial agents against the increasing
      bacterial resistance, novel cinnamaldehyde derivatives as FtsZ inhibitors were
      designed, synthesized and evaluated for their antibacterial activity against nine
      significant pathogens using broth microdilution method, and their cell division
      inhibitory activity against four representative strains. In the in vitro
      antibacterial activity, the newly synthesized compounds generally displayed
      better efficacy against Staphylococcus aureus ATCC25923 than the others. In
      particular, compounds 3, 8 and 10 exerted superior or comparable activity to all
      the reference drugs. In the cell division inhibitory activity, all the compounds
      showed the same trend as their in vitro antibacterial activity, exhibiting better
      activity against S. aureus ATCC25923 than the other strains. Additionally,
      compounds 3, 6, 7 and 8 displayed potent cell division inhibitory activity with
      an MIC value of below 1 MUg/mL, over 256-fold better than all the reference
      drugs. 

PMID- 25938987
TI  - Is RK-682 a promiscuous enzyme inhibitor? Synthesis and in vitro evaluation of
      protein tyrosine phosphatase inhibition of racemic RK-682 and analogues.
AB  - RK-682 (1) is a natural product known to selectively inhibit protein tyrosine
      phosphatases (PTPases) and is used commercially as a positive control for
      phosphatase inhibition in in vitro assays. Protein phosphatases are involved in
      several human diseases including diabetes, cancer and inflammation, and are
      considered important targets for pharmaceutical development. Here we report the
      synthesis of racemic RK-682 (rac-1) and a focused set of compounds, including
      racemic analogues of 1, dihydropyranones and C-acylated Meldrum's acid
      derivatives, the later obtained in one synthetic step from commercially available
      starting material. We further characterized the behavior of some representative
      compounds in aqueous solution and evaluated their in vitro PTPase binding and
      inhibition. Our data reveal that rac-1 and some derivatives are able to form
      large aggregates in solution, in which the aggregation capacity is dependent on
      the acyl side chain size. However, compound aggregation per se is not able to
      promote PTPase inhibition. Our data disclose a novel family of PTPase inhibitors
      (C-acylated Meldrum's acid derivatives) and that rac-1 and derivatives with an
      exposed latent negatively charged substructure (e.g.: the tetronic acid core of
      1) can bind to the PTPase binding site, as well promiscuously to protein
      surfaces. The combined capacity of compounds to bind to proteins together with
      their intrinsic capacity to aggregate in solution seems essential to promote
      enzyme aggregation and thus, its inhibition. We also observed that divalent
      cations, such as magnesium frequently used in enzyme buffer solutions, can
      deplete the inhibitory activity of rac-1, thus influencing the enzyme inhibition
      experiment. Overall, these data help to characterize the mechanism of PTPase
      inhibition by rac-1 and derivatives, revealing that enzyme inhibition is not
      solely dependent on compound binding to the PTPase catalytic site as generally
      accepted in the literature. In addition, our results point to promiscuous
      mechanisms that influence significantly the in vitro evaluation of enzyme
      inhibition by rac-1. Therefore, we recommend caution when using natural or
      synthetic RK-682 (1) as an internal control for evaluating PTPase inhibition and
      selectivity, since many events can modulate the apparent enzyme inhibition. 

PMID- 25938988
TI  - Shape-Tailorable Graphene-Based Ultra-High-Rate Supercapacitor for Wearable
      Electronics.
AB  - With the bloom of wearable electronics, it is becoming necessary to develop
      energy storage units, e.g., supercapacitors that can be arbitrarily tailored at
      the device level. Although gel electrolytes have been applied in supercapacitors
      for decades, no report has studied the shape-tailorable capability of a
      supercapacitor, for instance, where the device still works after being cut. Here
      we report a tailorable gel-based supercapacitor with symmetric electrodes
      prepared by combining electrochemically reduced graphene oxide deposited on a
      nickel nanocone array current collector with a unique packaging method. This
      supercapacitor with good flexibility and consistency showed excellent rate
      performance, cycling stability, and mechanical properties. As a demonstration,
      these tailorable supercapacitors connected in series can be used to drive small
      gadgets, e.g., a light-emitting diode (LED) and a minimotor propeller. As simple
      as it is (electrochemical deposition, stencil printing, etc.), this technique can
      be used in wearable electronics and miniaturized device applications that require
      arbitrarily shaped energy storage units. 

PMID- 25938989
TI  - Postmenopausal Symptoms in Female Veterans with Type 2 Diabetes: Glucose Control
      and Symptom Severity.
AB  - BACKGROUND: While type 2 diabetes mellitus (DM) is a common condition of midlife
      women, few studies have examined its influence on the symptom features of
      menopause. To explore this relationship, we conducted a study of symptom patterns
      of diabetic patients using a random sample of female veterans receiving care in
      the Veterans Affairs Healthcare system. METHODS: A cross-sectional comparison was
      conducted with three groups of postmenopausal respondents (ages 45-60 years) to a
      mailed national survey who also consented to clinical data access: no diabetes
      (n=90), diabetes with better glucose control (hemoglobin A1c [HbA1c]<=7%, n=135)
      and diabetes with worse glucose control (HbA1c>7%, n=102). RESULTS: Respondents,
      on average, were obese (body mass index: 33.9+/-0.4 kg/m(2)), 11.30+/-0.2 years
      postmenopause, with more than one chronic illness. Despite higher body mass index
      and increased comorbidities in women with diabetes compared with nondiabetic
      women, measures of mental health (anxiety, depressed mood, stress) were similar
      across groups. The pattern of menopause symptoms did not differ by group. Muscle
      aches/joint pain was the most prevalent symptom (78.6%), followed by vasomotor
      symptoms (74.4%). Respondents with elevated HbA1c demonstrated higher total
      menopausal symptom severity scores (DM-HbA1c>7: 15.4+/-0.8 vs. DM-HbA1c<=7%:
      12.2+/-0.8 vs. No diabetes: 12.3+/-0.8; p=0.006) than the other two groups.
      CONCLUSIONS: In postmenopausal female veterans with diabetes, glucose control is
      associated with the severity of those symptoms commonly attributed to menopause.
      Joint pain is an important part of the postmenopausal symptom complex in this
      population.

PMID- 25938990
TI  - Low-molecular-weight heparin for women with unexplained recurrent pregnancy loss:
      a multicenter trial with a minimization randomization scheme.
AB  - BACKGROUND: A daily injection of low-molecular-weight heparin (LMWH) is often
      prescribed to women with unexplained recurrent pregnancy loss (RPL), although
      evidence suggesting a benefit is questionable. OBJECTIVE: To determine whether
      LMWH increases ongoing pregnancy and live-birth rates in women with unexplained
      RPL. DESIGN: Controlled, multicenter trial with randomization using minimization
      conducted from 2006 to 2013. (ClinicalTrials.gov: NCT00400387). SETTING: 14
      university hospitals and perinatal care centers in Germany and Austria. PATIENTS:
      449 women with at least 2 consecutive early miscarriages or 1 late miscarriage
      were included during 5 to 8 weeks' gestation after a viable pregnancy was
      confirmed by ultrasonography. INTERVENTION: Women in the control group received
      multivitamin pills, and the intervention group received vitamins and 5000 IU of
      dalteparin-sodium for up to 24 weeks' gestation. MEASUREMENTS: Primary outcome
      was ongoing pregnancy at 24 weeks' gestation. Secondary outcomes included the
      live-birth rate and late pregnancy complications. RESULTS: At 24 weeks'
      gestation, 191 of 220 pregnancies (86.8%) and 188 of 214 pregnancies (87.9%) were
      intact in the intervention and control groups, respectively (absolute difference,
      -1.1 percentage points [95% CI, -7.4 to 5.3 percentage points]). The live-birth
      rates were 86.0% (185 of 215 women) and 86.7% (183 of 211 women) in the
      intervention and control groups, respectively (absolute difference, -0.7
      percentage point [CI, -7.3 to 5.9 percentage points]). There were 3 intrauterine
      fetal deaths (1 woman had used LMWH); 9 cases of preeclampsia or the hemolysis,
      elevated liver enzyme level, and low platelet count (HELLP) syndrome (3 women had
      used LMWH); and 11 cases of intrauterine growth restriction or placental
      insufficiency (5 women had used LMWH). LIMITATION: Placebo injections were not
      used, and neither trial staff nor patients were blinded. CONCLUSION: Daily LMWH
      injections do not increase ongoing pregnancy or live-birth rates in women with
      unexplained RPL. Given the burden of the injections, they are not recommended for
      preventing miscarriage. PRIMARY FUNDING SOURCE: Pfizer Pharma.

PMID- 25938991
TI  - The obesity paradox in type 2 diabetes mellitus: relationship of body mass index
      to prognosis: a cohort study.
AB  - BACKGROUND: Whether obesity is associated with a better prognosis in patients
      with type 2 diabetes mellitus is controversial. OBJECTIVE: To investigate the
      association between body weight and prognosis in a large cohort of patients with
      type 2 diabetes followed for a prolonged period. DESIGN: Prospective cohort.
      SETTING: National Health Service, England. PATIENTS: Patients with diabetes.
      MEASUREMENTS: The relationship between body mass index (BMI) and prognosis in
      patients with type 2 diabetes without known cardiovascular disease at baseline
      was investigated. Information on all-cause mortality and cardiovascular morbidity
      (such as the acute coronary syndrome, cerebrovascular accidents, and heart
      failure) was collected. Cox regression survival analysis, corrected for potential
      modifiers, including cardiovascular risk factors and comorbid conditions (such as
      cancer, chronic kidney disease, and lung disease), was done. RESULTS: 10,568
      patients were followed for a median of 10.6 years (interquartile range, 7.8 to
      13.4). Median age was 63 years (interquartile range, 55 to 71), and 54% of
      patients were men. Overweight or obese patients (BMI >25 kg/m2) had a higher rate
      of cardiac events (such as the acute coronary syndrome and heart failure) than
      those of normal weight (BMI, 18.5 to 24.9 kg/m2). However, being overweight (BMI,
      25 to 29.9 kg/m2) was associated with a lower mortality risk, whereas obese
      patients (BMI >30 kg/m2) had a mortality risk similar to that of normal-weight
      persons. Patients with low body weight had the worst prognosis. LIMITATION: Data
      about cause of death were not available. CONCLUSION: In this cohort, patients
      with type 2 diabetes who were overweight or obese were more likely to be
      hospitalized for cardiovascular reasons. Being overweight was associated with a
      lower mortality risk, but being obese was not. PRIMARY FUNDING SOURCE: National
      Institute for Health Research and University of Hull.

PMID- 25938992
TI  - Fecal Microbiota Transplantation for Clostridium difficile Infection: A
      Systematic Review.
AB  - BACKGROUND: The role of fecal microbiota transplantation (FMT) for Clostridium
      difficile infection (CDI) is not well-known. PURPOSE: To assess the efficacy,
      comparative effectiveness, and harms of FMT for CDI. DATA SOURCES: MEDLINE (1980
      to January 2015), Cochrane Library, and ClinicalTrials.gov, followed by hand
      searching references from systematic reviews and identified studies. STUDY
      SELECTION: Any study of FMT to treat adult patients with CDI; case reports were
      only used to report harms. DATA EXTRACTION: Data were extracted by 1 author and
      verified by another; 2 authors independently assessed risk of bias and strength
      of evidence. DATA SYNTHESIS: Two randomized, controlled trials (RCTs); 28 case
      series studies; and 5 case reports were included. Two RCTs and 21 case-series
      studies (516 patients receiving FMT) reported using FMT for patients with
      recurrent CDI. A high proportion of treated patients had symptom resolution;
      however, the role of previous antimicrobials is unclear. One RCT comparing FMT
      with 2 control groups (n = 43) reported resolution of symptoms in 81%, 31%, and
      23% of the FMT, vancomycin, or vancomycin-plus-bowel lavage groups, respectively
      (P < 0.001 for both control groups vs. FMT). An RCT comparing FMT route (n = 20)
      reported no difference between groups (60% in the nasogastric tube group and 80%
      in the colonoscopy group; P = 0.63). Across all studies for recurrent CDI,
      symptom resolution was seen in 85% of cases. In 7 case-series studies of patients
      with refractory CDI, symptom resolution ranged from 0% to 100%. Among 7 patients
      treated with FMT for initial CDI, results were mixed. LIMITATION: Most studies
      were uncontrolled case-series studies; only 2 RCTs were available for analysis.
      CONCLUSION: Fecal microbiota transplantation may have a substantial effect with
      few short-term adverse events for recurrent CDI. Evidence is insufficient on FMT
      for refractory or initial CDI treatment and on whether effects vary by donor,
      preparation, or delivery method. PRIMARY FUNDING SOURCE: U.S. Department of
      Veterans Affairs.

PMID- 25938993
TI  - A commitment to high-value care education from the internal medicine community.
AB  - The Alliance for Academic Internal Medicine, American Board of Internal Medicine
      (ABIM), ABIM Foundation, and American College of Physicians are collaborating to
      enhance the education of physicians in high-value care (HVC) and make its
      practice an essential competency in undergraduate and postgraduate education by
      2017. This article serves as the organizations' formal commitment to providing a
      foundation of HVC education on which others may build. The 5 key targets for HVC
      education are experiential learning and curriculum, environment and culture,
      clinical support, regulatory requirements, and sustainability. The goal is to
      train future health care professionals for whom HVC is part of normal practice,
      thus providing patients with improved clinical outcomes at a lower cost. 

PMID- 25938994
TI  - A startling injustice: pain, opioids, and addiction.

PMID- 25938995
TI  - Celebrating the ACP Centennial: From the Annals Archive-Measles and Vaccination.

PMID- 25938996
TI  - Is there any future for low-molecular-weight heparin in the prevention of
      pregnancy loss?

PMID- 25938997
TI  - Fecal microbiota transplantation: what we know and what we need to know.

PMID- 25938998
TI  - Not my place?

PMID- 25939000
TI  - Changes in mortality after Massachusetts health care reform.

PMID- 25939001
TI  - Changes in mortality after Massachusetts health care reform.

PMID- 25939002
TI  - Effects of nurse-managed protocols.

PMID- 25939003
TI  - The role of socioeconomic status in hospital outcomes measures.

PMID- 25939004
TI  - The role of socioeconomic status in hospital outcomes measures.

PMID- 25939005
TI  - D-Dimer Testing in Patients With a First Unprovoked Venous Thromboembolism.

PMID- 25939006
TI  - D-Dimer Testing in Patients With a First Unprovoked Venous Thromboembolism.

PMID- 25939007
TI  - Pharmacologic interventions for knee osteoarthritis.

PMID- 25939008
TI  - Pharmacologic interventions for knee osteoarthritis.

PMID- 25939011
TI  - Web Exclusives. Annals graphic medicine: 50 shades of gray matter.

PMID- 25939012
TI  - In the Clinic. Deep venous thrombosis.
AB  - This issue provides a clinical overview of deep venous thrombosis, focusing on
      prevention, diagnosis, treatment, and patient information. The content of In the
      Clinic is drawn from the clinical information and education resources of the
      American College of Physicians (ACP), including ACP Smart Medicine and MKSAP
      (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine
      editors develop In the Clinic from these primary sources in collaboration with
      the ACP's Medical Education and Publishing divisions and with the assistance of
      science writers and physician writers. Editorial consultants from ACP Smart
      Medicine and MKSAP provide expert review of the content. Readers who are
      interested in these primary resources for more detail can consult
      http://smartmedicine.acponline.org, http://mksap.acponline.org, and other
      resources referenced in each issue of In the Clinic. 

PMID- 25939013
TI  - Determining Membrane Protein Topology Using Fluorescence Protease Protection
      (FPP).
AB  - The correct topology and orientation of integral membrane proteins are essential
      for their proper function, yet such information has not been established for many
      membrane proteins. A simple technique called fluorescence protease protection
      (FPP) is presented, which permits the determination of membrane protein topology
      in living cells. This technique has numerous advantages over other methods for
      determining protein topology, in that it does not require the availability of
      multiple antibodies against various domains of the membrane protein, does not
      require large amounts of protein, and can be performed on living cells. The FPP
      method employs the spatially confined actions of proteases on the degradation of
      green fluorescent protein (GFP) tagged membrane proteins to determine their
      membrane topology and orientation. This simple approach is applicable to a wide
      variety of cell types, and can be used to determine membrane protein orientation
      in various subcellular organelles such as the mitochondria, Golgi, endoplasmic
      reticulum and components of the endosomal/recycling system. Membrane proteins,
      tagged on either the N-termini or C-termini with a GFP fusion, are expressed in a
      cell of interest, which is subject to selective permeabilization using the
      detergent digitonin. Digitonin has the ability to permeabilize the plasma
      membrane, while leaving intracellular organelles intact. GFP moieties exposed to
      the cytosol can be selectively degraded through the application of protease,
      whereas GFP moieties present in the lumen of organelles are protected from the
      protease and remain intact. The FPP assay is straightforward, and results can be
      obtained rapidly. 

PMID- 25939014
TI  - Land-use and carbon cycle responses to moderate climate change: implications for
      land-based mitigation?
AB  - Climate change has impacts on agricultural yields, which could alter cropland
      requirements and hence deforestation rates. Thus, land-use responses to climate
      change might influence terrestrial carbon stocks. Moreover, climate change could
      alter the carbon storage capacity of the terrestrial biosphere and hence the land
      based mitigation potential. We use a global spatially explicit economic land-use
      optimization model to (a) estimate the mitigation potential of a climate policy
      that provides economic incentives for carbon stock conservation and enhancement,
      (b) simulate land-use and carbon cycle responses to moderate climate change
      (RCP2.6), and (c) investigate the combined effects throughout the 21st century.
      The climate policy immediately stops deforestation and strongly increases
      afforestation, resulting in a global mitigation potential of 191 GtC in 2100.
      Climate change increases terrestrial carbon stocks not only directly through
      enhanced carbon sequestration (62 GtC by 2100) but also indirectly through less
      deforestation due to higher crop yields (16 GtC by 2100). However, such
      beneficial climate impacts increase the potential of the climate policy only
      marginally, as the potential is already large under static climatic conditions.
      In the broader picture, this study highlights the importance of land-use dynamics
      for modeling carbon cycle responses to climate change in integrated assessment
      modeling. 

PMID- 25939016
TI  - Internet-based cognitive-behavior therapy for procrastination: A randomized
      controlled trial.
AB  - OBJECTIVE: Procrastination can be a persistent behavior pattern associated with
      personal distress. However, research investigating different treatment
      interventions is scarce, and no randomized controlled trial has examined the
      efficacy of cognitive-behavior therapy (CBT). Meanwhile, Internet-based CBT has
      been found promising for several conditions, but has not yet been used for
      procrastination. METHOD: Participants (N = 150) were randomized to guided self
      help, unguided self-help, and wait-list control. Outcome measures were
      administered before and after treatment, or weekly throughout the treatment
      period. They included the Pure Procrastination Scale, the Irrational
      Procrastination Scale, the Susceptibility to Temptation Scale, the Montgomery
      Asberg Depression Rating Scale-Self-report version, the Generalized Anxiety
      Disorder Assessment, and the Quality of Life Inventory. The intention-to-treat
      principle was used for all statistical analyses. RESULTS: Mixed-effects models
      revealed moderate between-groups effect sizes comparing guided and unguided self
      help with wait-list control; the Pure Procrastination Scale, Cohen's d = 0.70,
      95% confidence interval (CI) [0.29, 1.10], and d = 0.50, 95% CI [0.10, 0.90], and
      the Irrational Procrastination Scale, d = 0.81 95% CI [0.40, 1.22], and d = 0.69
      95% CI [0.29, 1.09]. Clinically significant change was achieved among 31.3-40.0%
      for guided self-help, compared with 24.0-36.0% for unguided self-help. Neither of
      the treatment conditions was found to be superior on any of the outcome measures,
      Fs(98, 65.17-72.55) < 1.70, p > .19. CONCLUSION: Internet-based CBT could be
      useful for managing self-reported difficulties due to procrastination, both with
      and without the guidance of a therapist.

PMID- 25939015
TI  - Which Stage of ADPKD Is More Appropriate for Decortication? A Retrospective Study
      of 137 Patients from a Single Clinic.
AB  - OBJECTIVE: To study retrospectively the efficacy of decortication in patients
      with different stages of ADPKD and to determine which stage for decortication is
      more appropriate. MATERIALS AND METHODS: We analyzed 137 patients with ADPKD from
      2001 to 2010. All patients were divided into three stages. A total of 70 patients
      underwent decortication, and we studied intraoperative indicators and
      postoperative indicators at 1 and 3 years follow-up. RESULTS: In 70 patients who
      underwent decortication, significant differences were observed in operative
      duration and bleeding volume between patients with stage I and II ADPKD (P<0.05),
      but no significant differences were observed in intestinal recovery time, pain
      medication dose, and the days of postoperative hospitalization (P > 0.05). The
      total complication occurrence rate was significantly different between them (P <
      0.05). The serum creatinine (Scr) levels in patients with stage I ADPKD were
      within normal limits 1 and 3 years postoperatively and did not differ
      significantly (P > 0.05). Scr levels were significantly decreased in patients
      with stage II ADPKD in the 1st postoperative year (P < 0.05), but these were not
      significant differences in the 3rd postoperative year (P > 0.05). In the 1st
      postoperative year, VAS value, blood pressure and renal volume significantly
      differed (P < 0.05). However, no significant differences were observed 3 years
      later (P > 0.05). CONCLUSIONS: Decortication in patients with stage I ADPKD can
      alleviate back pain symptoms and decrease blood pressure within 1 year, but the
      long-term efficacy is not ideal. Scr levels can be maintained within normal
      limits, suggesting that decortication does not lead to deterioration of renal
      function. For patients with stage II ADPKD, decortication can significantly
      improve renal function over the short term. However, after 3 years, renal
      function returns to the preoperative level, and surgical difficulties and
      complications also increase.

PMID- 25939018
TI  - A randomized clinical trial of group cognitive processing therapy compared with
      group present-centered therapy for PTSD among active duty military personnel.
AB  - OBJECTIVE: To determine whether group therapy improves symptoms of posttraumatic
      stress disorder (PTSD), this randomized clinical trial compared efficacy of group
      cognitive processing therapy (cognitive only version; CPT-C) with group present
      centered therapy (PCT) for active duty military personnel. METHOD: Patients
      attended 90-min groups twice weekly for 6 weeks at Fort Hood, Texas. Independent
      assessments were administered at baseline, weekly before sessions, and 2 weeks, 6
      months, and 12 months posttreatment. A total of 108 service members (100 men, 8
      women) were randomized. Inclusion criteria included PTSD following military
      deployment and medication stability. Exclusion criteria included
      suicidal/homicidal intent or other severe mental disorders requiring immediate
      treatment. Follow-up assessments were administered regardless of treatment
      completion. Primary outcome measures were the PTSD Checklist (Stressor Specific
      Version; PCL-S) and Beck Depression Inventory-II. The Posttraumatic Stress
      Symptom Interview (PSS-1) was a secondary measure. RESULTS: Both treatments
      resulted in large reductions in PTSD severity, but improvement was greater in CPT
      C. CPT-C also reduced depression, with gains remaining during follow-up. In PCT,
      depression only improved between baseline and before Session 1. There were few
      adverse events associated with either treatment. CONCLUSIONS: Both CPT-C and PCT
      were tolerated well and reduced PTSD symptoms in group format, but only CPT-C
      improved depression. This study has public policy implications because of the
      number of active military needing PTSD treatment, and demonstrates that group
      format of treatment of PTSD results in significant improvement and is well
      tolerated. Group therapy may an important format in settings in which therapists
      are limited.

PMID- 25939017
TI  - Brief cognitive-behavioral and relaxation training interventions for breast
      cancer: A randomized controlled trial.
AB  - OBJECTIVE: Women with breast cancer (BCa) report elevated distress postsurgery.
      Group-based cognitive-behavioral stress management (CBSM) following surgery
      improves psychological adaptation, though its key mechanisms remain speculative.
      This randomized controlled dismantling trial compared 2 interventions featuring
      elements thought to drive CBSM effects: a 5-week cognitive-behavioral training
      (CBT) and 5-week relaxation training (RT) versus a 5-week health education (HE)
      control group. METHOD: Women with stage 0-III BCa (N = 183) were randomized to
      CBT, RT, or HE condition 2-10 weeks postsurgery. Psychosocial measures were
      collected at baseline (T1) and postintervention (T2). Repeated-measures analyses
      of variance (ANOVAs) tested whether CBT and RT treatments improved primary
      measures of psychological adaptation and secondary measures of stress management
      resource perceptions from pre- to postintervention relative to HE. RESULTS: Both
      CBT and RT groups reported reduced depressive affect. The CBT group reported
      improved emotional well-being/quality of life and less cancer-specific thought
      intrusions. The RT group reported improvements on illness-related social
      disruption. Regarding stress management resources, the CBT group reported
      increased reliability of social support networks, while the RT group reported
      increased confidence in relaxation skills. Psychological adaptation and stress
      management resource constructs were unchanged in the HE control group.
      CONCLUSIONS: Nonmetastatic breast cancer patients participating in 2 forms of
      brief, 5-week group-based stress management intervention after surgery showed
      improvements in psychological adaptation and stress management resources compared
      with an attention-matched control group. Findings provide preliminary support
      suggesting that using brief group-based stress management interventions may
      promote adaptation among nonmetastatic breast cancer patients.

PMID- 25939019
TI  - Effects of a combined parent-student alcohol prevention program on intermediate
      factors and adolescents' drinking behavior: A sequential mediation model.
AB  - OBJECTIVE: Previous work revealed that the combined parent-student alcohol
      prevention program (PAS) effectively postponed alcohol initiation through its
      hypothesized intermediate factors: increase in strict parental rule setting and
      adolescents' self-control (Koning, van den Eijnden, Verdurmen, Engels, &
      Vollebergh, 2011). This study examines whether the parental strictness precedes
      an increase in adolescents' self-control by testing a sequential mediation model.
      METHODS: A cluster randomized trial including 3,245 Dutch early adolescents (M
      age = 12.68, SD = 0.50) and their parents randomized over 4 conditions: (1)
      parent intervention, (2) student intervention, (3) combined intervention, and (4)
      control group. Outcome measure was amount of weekly drinking measured at age 12
      to 15; baseline assessment (T0) and 3 follow-up assessments (T1-T3). RESULTS:
      Main effects of the combined and parent intervention on weekly drinking at T3
      were found. The effect of the combined intervention on weekly drinking (T3) was
      mediated via an increase in strict rule setting (T1) and adolescents' subsequent
      self-control (T2). In addition, the indirect effect of the combined intervention
      via rule setting (T1) was significant. No reciprocal sequential mediation (self
      control at T1 prior to rules at T2) was found. CONCLUSIONS: The current study is
      1 of the few studies reporting sequential mediation effects of youth intervention
      outcomes. It underscores the need of involving parents in youth alcohol
      prevention programs, and the need to target both parents and adolescents, so that
      change in parents' behavior enables change in their offspring.

PMID- 25939020
TI  - Copper binding to the N-terminally acetylated, naturally occurring form of alpha
      synuclein induces local helical folding.
AB  - Growing evidence supports a link between brain copper homeostasis, the formation
      of alpha-synuclein (AS)-copper complexes, and the development of Parkinson
      disease (PD). Recently it was demonstrated that the physiological form of AS is N
      terminally acetylated (AcAS). Here we used NMR spectroscopy to structurally
      characterize the interaction between Cu(I) and AcAS. We found that the formation
      of an AcAS-Cu(I) complex at the N-terminal region stabilizes local conformations
      with alpha-helical secondary structure and restricted motility. Our work provides
      new evidence into the metallo-biology of PD and opens new lines of research as
      the formation of AcAS-Cu(I) complex might impact on AcAS membrane binding and
      aggregation. 

PMID- 25939021
TI  - Rapid access to spirocylic oxindoles: application of asymmetric N-heterocyclic
      carbene-catalyzed [3 + 3] cycloaddition of imines to oxindole-derived enals.
AB  - A chiral N-heterocyclic carbene (NHC)-catalyzed [3 + 3] cycloaddition reaction of
      imines and oxindole-derived enals was developed for rapid access to spirocylic
      oxindoles. In most cases, the desired spirocylic oxindole products were obtained
      in high yields and excellent enantioselectivities with less than 1 h of reaction
      time. 

PMID- 25939022
TI  - An inexpensive, scalable behavioral assay for measuring ethanol sedation
      sensitivity and rapid tolerance in Drosophila.
AB  - Alcohol use disorder (AUD) is a serious health challenge. Despite a large
      hereditary component to AUD, few genes have been unambiguously implicated in
      their etiology. The fruit fly, Drosophila melanogaster, is a powerful model for
      exploring molecular-genetic mechanisms underlying alcohol-related behaviors and
      therefore holds great promise for identifying and understanding the function of
      genes that influence AUD. The use of the Drosophila model for these types of
      studies depends on the availability of assays that reliably measure behavioral
      responses to ethanol. This report describes an assay suitable for assessing
      ethanol sensitivity and rapid tolerance in flies. Ethanol sensitivity measured in
      this assay is influenced by the volume and concentration of ethanol used, a
      variety of previously reported genetic manipulations, and also the length of time
      the flies are housed without food immediately prior to testing. In contrast,
      ethanol sensitivity measured in this assay is not affected by the vigor of fly
      handling, sex of the flies, and supplementation of growth medium with antibiotics
      or live yeast. Three different methods for quantitating ethanol sensitivity are
      described, all leading to essentially indistinguishable ethanol sensitivity
      results. The scalable nature of this assay, combined with its overall simplicity
      to set-up and relatively low expense, make it suitable for small and large scale
      genetic analysis of ethanol sensitivity and rapid tolerance in Drosophila. 

PMID- 25939023
TI  - Remarkable electrokinetic features of charge-stratified soft nanoparticles:
      mobility reversal in monovalent aqueous electrolyte.
AB  - The electrokinetic behavior of G6.5 carboxylate-terminated poly(amidoamine)
      (PAMAM) starburst dendrimers (8 +/- 1 nm diameter) is investigated over a broad
      range of pH values (3-9) and NaNO3 concentrations (c(infinity )= 2-200 mM). The
      dependence of nanodendrimer electrophoretic mobility MU on pH and c(infinity) is
      marked by an unconventional decrease of the point of zero mobility (PZM) from 5.4
      to 5.5 to 3.8 upon increase in salt concentration, with PZM defined as the pH
      value at which a reversal of the mobility sign is reached. The existence of a
      common intersection point is further evidenced for series of mobility versus pH
      curves measured at different NaNO3 concentrations. Using soft particle
      electrokinetic theory, this remarkable behavior is shown to originate from the
      zwitterionic functionality of the PAMAM-COOH particles. The dependence of PZM on
      c(infinity) results from the coupling between electroosmotic flow and dendrimeric
      interphase defined by a nonuniform distribution of amine and carboxylic
      functional groups. In turn, MU reflects the sign and distribution of particle
      charges located within an electrokinetically active region, the dimension of
      which is determined by the Debye length, varied here in the range 0.7-6.8 nm. In
      agreement with theory, the electrokinetics of smaller G4.5 PAMAM-COOH
      nanoparticles (5 +/- 0.5 nm diameter) further confirms that the PZM is shifted to
      higher pH with decreasing dendrimer size. Depending on pH, a mobility extremum is
      obtained under conditions where the Debye length and the particle radius are
      comparable. This results from changes in particle structure compactness following
      salt- and pH-mediated modulations of intraparticle Coulombic interactions. The
      findings solidly evidence the possible occurrence of particle mobility reversal
      in monovalent salt solution suggested by recent molecular dynamic simulations and
      anticipated from earlier mean-field electrokinetic theory. 

PMID- 25939024
TI  - Peripheral regulatory T lymphocytes recirculating to the thymus suppress the
      development of their precursors.
AB  - Most T lymphocytes, including regulatory T cells (Treg cells), differentiate in
      the thymus. The age-dependent involution of this organ leads to decreasing
      production of T cells. Here we found that the output of new Treg cells from the
      thymus decreased substantially more than that of conventional T cells. Peripheral
      mouse and human Treg cells recirculated back to the thymus, where they
      constituted a large proportion of the pool of Treg cells and displayed an
      activated and differentiated phenotype. In the thymus, the recirculating cells
      exerted their regulatory function by inhibiting interleukin 2 (IL-2)-dependent de
      novo differentiation of Treg cells. Thus, Treg cell development is controlled by
      a negative feedback loop in which mature progeny cells return to the thymus and
      restrain development of precursors of Treg cells. 

PMID- 25939025
TI  - The ubiquitin-modifying enzyme A20 restricts ubiquitination of the kinase RIPK3
      and protects cells from necroptosis.
AB  - A20 is an anti-inflammatory protein linked to multiple human diseases; however,
      the mechanisms by which A20 prevents inflammatory disease are incompletely
      defined. We found that A20-deficient T cells and fibroblasts were susceptible to
      caspase-independent and kinase RIPK3-dependent necroptosis. Global deficiency in
      RIPK3 significantly restored the survival of A20-deficient mice. A20-deficient
      cells exhibited exaggerated formation of RIPK1-RIPK3 complexes. RIPK3 underwent
      physiological ubiquitination at Lys5 (K5), and this ubiquitination event
      supported the formation of RIPK1-RIPK3 complexes. Both the ubiquitination of
      RIPK3 and formation of the RIPK1-RIPK3 complex required the catalytic cysteine of
      A20's deubiquitinating motif. Our studies link A20 and the ubiquitination of
      RIPK3 to necroptotic cell death and suggest additional mechanisms by which A20
      might prevent inflammatory disease. 

PMID- 25939027
TI  - The challenge of offering long-acting antipsychotic therapies: a preliminary
      discourse analysis of psychiatrist recommendations for injectable therapy to
      patients with schizophrenia.
AB  - OBJECTIVE: To characterize patterns of communication in the offer of long-acting
      injectable (LAI) antipsychotic medication made by psychiatrists to patients with
      schizophrenia by (1) examining the style and content of their interaction and (2)
      determining how these may have driven the ultimate response to recommendations
      for LAI therapy. METHOD: This was an observational study conducted at 10
      community mental health centers in 3 waves from July 2010 to May 2011. The final
      dataset for discourse analysis was 33 recorded conversations in which a
      psychiatrist offered an injectable antipsychotic to a patient with schizophrenia.
      These visits were transcribed and analyzed by a team of linguists and social
      scientists. RESULTS: Our primary finding is that, based on analyses of their
      language during the interview, psychiatrists presented LAI therapy in a negative
      light. Supporting this, 11 of 33 recommendations (33%) were accepted during the
      discussion, whereas in the postvisit interview, 27 of 28 patients (96%) who
      seemed to decline the initial recommendation said they actually would be willing
      to try LAI treatment. CONCLUSIONS: These data support a preliminary hypothesis
      that the relatively low use of injectable antipsychotic therapies in the United
      States relative to other parts of the world is not fully attributable to patient
      rejection of the injectable modality. Rather, psychiatrists' ambivalence
      regarding the value of LAIs may play a significant role in the perceived
      difficulty with patient acceptance of this recommendation.

PMID- 25939026
TI  - Thymic regulatory T cell niche size is dictated by limiting IL-2 from antigen
      bearing dendritic cells and feedback competition.
AB  - The thymic production of regulatory T cells (Treg cells) requires interleukin 2
      (IL-2) and agonist T cell antigen receptor (TCR) ligands and is controlled by
      competition for a limited developmental niche, but the thymic sources of IL-2 and
      the factors that limit access to the niche are poorly understood. Here we found
      that IL-2 produced by antigen-bearing dendritic cells (DCs) had a key role in
      Treg cell development and that existing Treg cells limited new development of
      Treg cells by competing for IL-2. Our data suggest that antigen-presenting cells
      (APCs) that can provide both IL-2 and a TCR ligand constitute the thymic niche
      and that competition by existing Treg cells for a limited supply of IL-2 provides
      negative feedback for new production of Treg cells. 

PMID- 25939028
TI  - In silico Driven Pharmacognosy: Forth, Back and Reverse.

PMID- 25939030
TI  - The effects of expressive writing on lung function, quality of life, medication
      use, and symptoms in adults with asthma: a randomized controlled trial.
AB  - OBJECTIVES: Asthma is a chronic condition affecting 300 million people worldwide.
      Management involves adherence to pharmacological treatments such as
      corticosteroids and beta-agonists, but residual symptoms persist. As asthma
      symptoms are exacerbated by stress, one possible adjunct to pharmacological
      treatment is expressive writing (EW). EW involves the disclosure of traumatic
      experiences which is thought to facilitate cognitive and emotional processing,
      helping to reduce physiological stress associated with inhibiting emotions. A
      previous trial reported short-term improvements in lung function. This study
      aimed to assess whether EW can improve lung function, quality of life, symptoms,
      and medication use in patients with asthma. METHODS: Adults (18-45 years)
      diagnosed as having asthma requiring regular inhaled corticosteroids were
      recruited from 28 general practices in South East England (n = 146). In this
      double-blind randomized controlled trial, participants were allocated either EW
      or nonemotional writing instructions and asked to write for 20 minutes for 3
      consecutive days. Lung function (forced expired volume in 1 second [FEV1]%
      predicted), quality of life (Mark's Asthma Quality of Life Questionnaire), asthma
      symptoms (Wasserfallen Symptom Score Questionnaire), and medication use (inhaled
      corticosteroids and beta-agonist) were recorded at baseline, 1, 3, 6, and 12
      months. RESULTS: Hierarchical linear modeling indicated no significant main
      effects between time and condition on any outcomes. Post hoc analyses revealed
      that EW improved lung function by 14% for 12 months for participants with less
      than 80% FEV1% predicted at baseline (beta = 0.93, p = .002) whereas no
      improvement was observed in the control condition (beta = 0.10, p = .667).
      CONCLUSIONS: EW seems to be beneficial for patients with moderate asthma (<80%
      FEV1% predicted). Future studies of EW require stratification of patients by
      asthma severity. TRIAL REGISTRATION: ISRCTN82986307.

PMID- 25939031
TI  - Physical activity report cards: Active Healthy Kids Global Alliance and The
      Lancet Physical Activity Observatory.

PMID- 25939029
TI  - Interferon Gamma +874T/A Polymorphism Increases the Risk of Hepatitis Virus
      Related Diseases: Evidence from a Meta-Analysis.
AB  - BACKGROUND: Interferon gamma (IFN-gamma) is a key regulatory cytokine, which
      plays an important role in antiviral defense of an infected host. However, the
      association between the IFN-gamma +874T/A gene polymorphism and hepatitis virus
      related diseases is heterogeneous. METHODS: Based on the Preferred Reporting
      Items for Systematic Reviews and Meta-analyses statement, a comprehensive
      literature search of eligible studies in Embase, Pubmed, and the Cochrane Library
      was undertaken through November 2014. Odds ratios (ORs) and the corresponding 95%
      confidence intervals (CIs) were used to measure the strength of the models.
      RESULTS: Seventeen case-control articles, including 24 studies with 5503
      individuals, met the inclusion criteria. The results indicated a statistically
      significant association between the IFN-gamma +874T/A polymorphism and hepatitis
      virus-related diseases in a recessive gene model (AA vs. TT+TA: OR=1.350, 95%
      CI=1.101-1.657, P=0.004, I2%=54.3, and PQ=0.001 for heterogeneity), especially in
      Asians (OR=1.407, 95% CI=1.035-1.911, P=0.029, I2%=61.9, and PQ=0.005 for
      heterogeneity) and hepatitis B virus (HBV)-related disease (OR=1.486, 95%
      CI=1.195-1.849, P=0.000, I2%=40.4, and PQ=0.053 for heterogeneity). CONCLUSIONS:
      The evidence suggests that the IFN-gamma +874T/A polymorphism increases the risk
      of hepatitis virus-related diseases, especially in Asians and HBV-related
      diseases. Further studies on this topic in different ethnicities, especially
      genome-wide association studies, should be conducted to strengthen our results.

PMID- 25939032
TI  - Can non-pharmacological interventions prevent relapse in adults who have
      recovered from depression? A systematic review and meta-analysis of randomised
      controlled trials.
AB  - OBJECTIVE: To identify studies of non-pharmacological interventions provided
      following recovery from depression, and to evaluate their efficacy in preventing
      further episodes. METHOD: We identified relevant randomised controlled trials
      from searching MEDLINE, Embase, PsycINFO, CENTRAL, and ProQuest, searching
      reference and citation lists, and contacting study authors. We conducted a meta
      analysis of relapse outcomes. RESULTS: There were 29 eligible trials. 27 two-way
      comparisons including 2742 participants were included in the primary analysis. At
      12months cognitive-behavioural therapy (CBT), mindfulness-based cognitive therapy
      (MBCT), and interpersonal psychotherapy (IPT) were associated with a 22%
      reduction in relapse compared with controls (95% CI 15% to 29%). The effect was
      maintained at 24months for CBT, but not for IPT despite ongoing sessions. There
      were no 24-month MBCT data. A key area of heterogeneity differentiating these
      groups was prior acute treatment. Other psychological therapies and service-level
      programmes varied in efficacy. CONCLUSION AND IMPLICATIONS: Psychological
      interventions may prolong the recovery a person has achieved through use of
      medication or acute psychological therapy. Although there was evidence that MBCT
      is effective, it was largely tested following medication, so its efficacy
      following psychological interventions is less clear. IPT was only tested
      following acute IPT. Further exploration of sequencing of interventions is
      needed. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO 2011:CRD42011001646.

PMID- 25939033
TI  - Interventions to address parenting and parental substance abuse: conceptual and
      methodological considerations.
AB  - Parental substance abuse is a serious problem affecting the well-being of
      children and families. The co-occurrence of parental substance abuse and
      problematic parenting is recognized as a major public health concern. This review
      focuses on 21 outcome studies that tested dual treatment of substance abuse and
      parenting. A summary of theoretical conceptualizations of the connections between
      substance abuse and parenting provides a backdrop for the review. Outcomes of the
      dual treatment studies were generally positive with respect to reduction of
      parental substance use and improvement of parenting. Research in this area varied
      in methodological rigor and needs to overcome challenges regarding design issues,
      sampling frame, and complexities inherent in such a high-risk population. This
      area of work can be strengthened by randomized controlled trials, use of mixed
      methods outcome measures, consideration of parent involvement with child
      protective services, involvement of significant others in treatment, provision of
      concrete supports for treatment attendance and facilitative public policies. 

PMID- 25939036
TI  - Employment of marine polysaccharides to manufacture functional biocomposites for
      aquaculture feeding applications.
AB  - In this study, polysaccharides of marine origin (agar, alginate and kappa
      carrageenan) were used to embed nutrients to fabricate biocomposites to be
      employed in animal feeding. The consistency of biocomposites in water has been
      evaluated up to 14 days, by several methods: swelling, nutrient release and
      granulometric analysis. Biocomposites were produced with varying percentages of
      nutrients (5%-25%) and polysaccharides (1%-2%-3%). All possible biopolymer
      combinations were tested in order to select those with the best network strength.
      The best performing biocomposites were those manufactured with agar 2% and
      nutrients 10%, showing the lowest percentage of water absorption and nutrient
      release. Biocomposites made of agar 2% and nutrients 10% were the most stable in
      water and were therefore used to analyze their behavior in water with respect to
      the release of quercetin, a phenolic compound with demonstrated high
      antibacterial and antioxidant activities. The leaching of such molecules in water
      was therefore employed as a further indicator of biocomposite water stability.
      Altogether, our results confirm the suitability of agar as a binder for
      biocomposites and provide a positive contribution to aquaculture. 

PMID- 25939034
TI  - Diatom milking: a review and new approaches.
AB  - The rise of human populations and the growth of cities contribute to the
      depletion of natural resources, increase their cost, and create potential
      climatic changes. To overcome difficulties in supplying populations and reducing
      the resource cost, a search for alternative pharmaceutical, nanotechnology, and
      energy sources has begun. Among the alternative sources, microalgae are the most
      promising because they use carbon dioxide (CO2) to produce biomass and/or
      valuable compounds. Once produced, the biomass is ordinarily harvested and
      processed (downstream program). Drying, grinding, and extraction steps are
      destructive to the microalgal biomass that then needs to be renewed. The
      extraction and purification processes generate organic wastes and require
      substantial energy inputs. Altogether, it is urgent to develop alternative
      downstream processes. Among the possibilities, milking invokes the concept that
      the extraction should not kill the algal cells. Therefore, it does not require
      growing the algae anew. In this review, we discuss research on milking of
      diatoms. The main themes are (a) development of alternative methods to extract
      and harvest high added value compounds; (b) design of photobioreactors; 

PMID- 25939035
TI  - The Cytoprotective Effect of Petalonia binghamiae Methanol Extract against
      Oxidative Stress in C2C12 Myoblasts: Mediation by Upregulation of Heme Oxygenase
      1 and Nuclear Factor-Erythroid 2 Related Factor 2.
AB  - This study was designed to examine the protective effects of the marine brown
      algae Petalonia binghamiae against oxidative stress-induced cellular damage and
      to elucidate the underlying mechanisms. P. binghamiae methanol extract (PBME)
      prevented hydrogen peroxide (H2O2)-induced growth inhibition and exhibited
      scavenging activity against intracellular reactive oxygen species (ROS) induced
      by H2O2 in mouse-derived C2C12 myoblasts. PBME also significantly attenuated H2O2
      induced comet tail formation in a comet assay, histone gammaH2A.X
      phosphorylation, and annexin V-positive cells, suggesting that PBME prevented
      H2O2-induced cellular DNA damage and apoptotic cell death. Furthermore, PBME
      increased the levels of heme oxygenase-1 (HO-1), a potent antioxidant enzyme,
      associated with the induction of nuclear factor-erythroid 2 related factor 2
      (Nrf2). However, zinc protoporphyrin IX, a HO-1 competitive inhibitor,
      significantly abolished the protective effects of PBME on H2O2-induced ROS
      generation, growth inhibition, and apoptosis. Collectively, these results
      demonstrate that PBME augments the antioxidant defense capacity through
      activation of the Nrf2/HO-1 pathway. 

PMID- 25939037
TI  - Recent advances and applications of experimental technologies in marine natural
      product research.
AB  - Marine natural products are a rich source of novel and biologically active
      compounds. The number of identified marine natural compounds has grown 20% over
      the last five years from 2009 to 2013. Several challenges, including sample
      collection and structure elucidation, have limited the development of this
      research field. Nonetheless, new approaches, such as sampling strategies for
      organisms from extreme ocean environments, nanoscale NMR and computational
      chemistry for structural determination, are now available to overcome the
      barriers. In this review, we highlight the experimental technology innovations in
      the field of marine natural products, which in our view will lead to the
      development of many new drugs in the future. 

PMID- 25939038
TI  - Electrochemical Analysis of Neurotransmitters.
AB  - Chemical signaling through the release of neurotransmitters into the
      extracellular space is the primary means of communication between neurons. More
      than four decades ago, Ralph Adams and his colleagues realized the utility of
      electrochemical methods for the study of easily oxidizable neurotransmitters,
      such as dopamine, norepinephrine, and serotonin and their metabolites. Today,
      electrochemical techniques are frequently coupled to microelectrodes to enable
      spatially resolved recordings of rapid neurotransmitter dynamics in a variety of
      biological preparations spanning from single cells to the intact brain of
      behaving animals. In this review, we provide a basic overview of the principles
      underlying constant-potential amperometry and fast-scan cyclic voltammetry, the
      most commonly employed electrochemical techniques, and the general application of
      these methods to the study of neurotransmission. We thereafter discuss several
      recent developments in sensor design and experimental methodology that are
      challenging the current limitations defining the application of electrochemical
      methods to neurotransmitter measurements. 

PMID- 25939039
TI  - Colonic Insult Impairs Lymph Flow, Increases Cellular Content of the Lymph,
      Alters Local Lymphatic Microenvironment, and Leads to Sustained Inflammation in
      the Rat Ileum.
AB  - BACKGROUND: Lymphatic dysfunction has been linked to inflammation since the
      1930s. Lymphatic function in the gut and mesentery is grossly underexplored in
      models of inflammatory bowel disease despite the use of lymphatic occlusion in
      early models of inflammatory bowel disease. Activation of the innate and adaptive
      immune system is a hallmark of TNBS-induced inflammation and is linked to
      disruption of the intrinsic lymph pump. Recent identification of crosstalk
      between lymphatic vessel resident immune cells and regulation of lymphatic vessel
      contractility underscore the importance of the timing of lymphatic dysfunction
      during tissue inflammation in response to TNBS. METHODS: To evaluate lymphatic
      function in TNBS induced inflammation, lymph was collected and flow measured from
      mesenteric lymphatics. Cellularity and cytokine profile of the lymph was also
      measured. Histopathology was performed to determine severity of injury and
      immunofluorescent staining of the mesentery was done to evaluate changes in the
      population of immune cells that reside near and on gastro-intestinal collecting
      lymphatics. RESULTS: Lymph transport fell 24 hours after TNBS administration and
      began recovering at 72 hours. Significant reduction of lymph flow preceded
      significant increase in histopathological score and occurred simultaneously with
      increased myeloperoxidase activity. These changes were preceded by increased
      MHCII cells surrounding mesenteric lymphatics leading to an altered lymphatic
      environment that would favor dysfunction. CONCLUSIONS: Alterations in
      environmental factors that effect lymphatic function occur before the development
      of gross GI inflammation. Reduced lymphatic function in TNBS-mediated
      inflammation is likely an early factor in the development of injury and that
      recovery of function is associated with resolution of inflammation.

PMID- 25939040
TI  - Metagenomic analysis of microbiome in colon tissue from subjects with
      inflammatory bowel diseases reveals interplay of viruses and bacteria.
AB  - Inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis, are
      poorly understood disorders affecting the intestinal tract. The current model for
      disease suggests that genetically susceptible patients develop intolerance to gut
      microflora, and chronic inflammation develops as a result of environmental
      insults. Although interest has mainly focused on studying genetic variants and
      gut bacterial flora, little is known about the potential of viral infection to
      contribute to disease. Accordingly, we conducted a metagenomic analysis to
      document the baseline virome in colonic biopsy samples from patients with IBD in
      order to assess the contribution of viral infection to IBD. Libraries were
      generated from colon RNA to create approximately 2 GB sequence data per library.
      Using a bioinformatic pipeline designed to detect viral sequences, more than 1000
      viral reads were derived directly from tissue without any coculture or isolation
      procedure. Herein, we describe the complexity and abundance of viruses,
      bacteria/bacteriophage, and human endogenous retroviral sequences from 10
      patients with IBD and 5 healthy subjects undergoing surveillance colonoscopy.
      Differences in gut microflora and the abundance of mammalian viruses and human
      endogenous retroviruses were readily detected in the metagenomic analyses.
      Specifically, patients with herpesviridae sequences in their colon demonstrated
      increased expression of human endogenous viral sequences and differences in the
      diversity of their microbiome. This study provides a promising metagenomic
      approach to describe the colonic microbiome that can be used to better understand
      virus-host and phage-bacteria interactions in IBD. 

PMID- 25939041
TI  - Properdin Regulation of Complement Activation Affects Colitis in Interleukin 10
      Gene-Deficient Mice.
AB  - BACKGROUND: Interleukin 10-deficient mice (IL-10(-/-)) are a popular model used
      to dissect the mechanisms underlying inflammatory bowel diseases. The role of
      complement, a host defense mechanism that bridges the innate and adaptive immune
      systems, has not been described in this model. We therefore studied the effect of
      deficiency of properdin, a positive regulator of complement, on colitis in mice
      with the IL-10(-/-) background. METHODS: For acute colitis, IL-10(-/-) and IL
      10/properdin double knockout (DKO) or radiation bone marrow-reconstituted
      chimeric mice, had piroxicam added to their powdered chow for 14 days. For
      chronic colitis, 2.5% dextran sodium sulfate was added to the animals' water for
      4 days then the mice were killed 8 weeks later. Colons were assessed for
      inflammation, cell infiltration, and cytokine and complement measurements.
      Bacterial translocation was measured by cultivating bacteria from organs on Luria
      broth agar plates. RESULTS: C3a and C5a levels and C9 deposition were all
      increased in piroxicam-fed IL-10(-/-) mice compared with mice not fed piroxicam.
      Piroxicam-fed DKO mice lacked increased C5a and C9 deposition combined with
      exacerbated colitis, reduced numbers of infiltrating neutrophils, and markedly
      higher local and systemic bacterial numbers compared with IL-10(-/-) mice. Bone
      marrow cells from IL-10(-/-) mice were sufficient to restore protection against
      the heightened colitis in piroxicam-fed DKO mice. CONCLUSIONS: Complement is
      activated in the IL-10(-/-) mouse mucosa in a properdin-dependent manner. In the
      absence of terminal complement activation, the inflammation is heightened, likely
      due to a lack of neutrophil control over microbes escaping from the intestines.

PMID- 25939042
TI  - Reply to What is the Role of Diffusion-weighted Imaging in Ileocolonic Crohn's
      Disease?

PMID- 25939043
TI  - Reply to can fecal microbial transplant effectively treat Crohn's disease?

PMID- 25939044
TI  - Fish embryo toxicity test: identification of compounds with weak toxicity and
      analysis of behavioral effects to improve prediction of acute toxicity for
      neurotoxic compounds.
AB  - The fish embryo toxicity test has been proposed as an alternative for the acute
      fish toxicity test, but concerns have been raised for its predictivity given that
      a few compounds have been shown to exhibit a weak acute toxicity in the fish
      embryo. In order to better define the applicability domain and improve the
      predictive capacity of the fish embryo test, we performed a systematic analysis
      of existing fish embryo and acute fish toxicity data. A correlation analysis of a
      total of 153 compounds identified 28 compounds with a weaker or no toxicity in
      the fish embryo test. Eleven of these compounds exhibited a neurotoxic mode of
      action. We selected a subset of eight compounds with weaker or no embryo toxicity
      (cyanazine, picloram, aldicarb, azinphos-methyl, dieldrin, diquat dibromide,
      endosulfan, and esfenvalerate) to study toxicokinetics and a neurotoxic mode of
      action as potential reasons for the deviating fish embryo toxicity. Published
      fish embryo LC50 values were confirmed by experimental analysis of zebrafish
      embryo LC50 according to OECD guideline 236. Except for diquat dibromide,
      internal concentration analysis did not indicate a potential relation of the low
      sensitivity of fish embryos to a limited uptake of the compounds. Analysis of
      locomotor activity of diquat dibromide and the neurotoxic compounds in 98 hpf
      embryos (exposed for 96 h) indicated a specific effect on behavior (embryonic
      movement) for the neurotoxic compounds. The EC50s of behavior for neurotoxic
      compounds were close to the acute fish toxicity LC50. Our data provided the first
      evidence that the applicability domain of the fish embryo test (LC50s
      determination) may exclude neurotoxic compounds. However, neurotoxic compounds
      could be identified by changes in embryonic locomotion. Although a quantitative
      prediction of acute fish toxicity LC50 using behavioral assays in fish embryos
      may not yet be possible, the identification of neurotoxicity could trigger the
      conduction of a conventional fish acute toxicity test or application of
      assessment factors while considering the very good fish embryo-acute fish
      toxicity correlation for other compounds. 

PMID- 25939045
TI  - Diastereo- and Enantioselective Construction of 3,3'-Pyrrolidinyldispirooxindole
      Framework via Catalytic Asymmetric 1,3-Dipolar Cycloadditions.
AB  - The first catalytic enantioselective construction of a 3,3'
      pyrrolidinyldispirooxindole scaffold has been established via organocatalytic
      asymmetric 1,3-dipolar cycloadditions of isatin-derived azomethine ylides with
      methyleneindolinones, which afforded structurally complex bis-spirooxindoles
      containing three contiguous and two quaternary stereogenic centers in generally
      high yields (up to 99%) and excellent diastereo- and enantioselectivities (up to
      >95:5 dr, 98% ee). This reaction also provides a good example for the application
      of catalytic asymmetric 1,3-dipolar cycloadditions in constructing
      enantioenriched bis-spirooxindole frameworks with structural complexity and
      rigidity. 

PMID- 25939046
TI  - RNA Isolation from Cell Specific Subpopulations Using Laser-capture
      Microdissection Combined with Rapid Immunolabeling.
AB  - Laser capture microdissection (LCM) allows the isolation of specific cells from
      thin tissue sections with high spatial resolution. Effective LCM requires precise
      identification of cells subpopulations from a heterogeneous tissue.
      Identification of cells of interest for LCM is usually based on morphological
      criteria or on fluorescent protein reporters. The combination of LCM and rapid
      immunolabeling offers an alternative and efficient means to visualize specific
      cell types and to isolate them from surrounding tissue. High-quality RNA can then
      be extracted from a pure cell population and further processed for downstream
      applications, including RNA-sequencing, microarray or qRT-PCR. This approach has
      been previously performed and briefly described in few publications. The goal of
      this article is to illustrate how to perform rapid immunolabeling of a cell
      population while keeping RNA integrity, and how to isolate these specific cells
      using LCM. Herein, we illustrated this multi-step procedure by immunolabeling and
      capturing dopaminergic cells in brain tissue from one-day-old mice. We highlight
      key critical steps that deserve special consideration. This protocol can be
      adapted to a variety of tissues and cells of interest. Researchers from different
      fields will likely benefit from the demonstration of this approach. 

PMID- 25939047
TI  - The complete mitochondrial genome of Botia lohachata (Cypriniformes: Cobitidae).
AB  - In this study, the complete mitochondrial genome of Botia lohachata was
      determined (GenBank accession number KP729183). The mitochondrial genome sequence
      of B. lohachata was a circular molecule with 16,594 bp in length, and it
      contained 37 typical animal mitochondrial genes: 2 ribosomal RNA genes, 13
      protein-coding genes, 22 transfer RNA genes, an L-strand replication origin (OL)
      and a control region (D-loop). The nucleotide acid composition of the entire
      mitogenome was 26.53% C, 15.63% G, 31.98% A and 25.86% T, with an AT content of
      57.83%.

PMID- 25939048
TI  - The complete mitochondrial genome of Antheraea pernyi strain Yu6 (Lepidoptera:
      Saturniidae).
AB  - In this study, the complete mitochondrial genome of Antheraea pernyi strain Yu6
      (Lepidoptera: Saturniidae) has been reported for the first time. It is a circular
      molecule of 15,569 bp in length, containing 37 typical coding genes and 1 non
      coding AT-rich region. The overall composition of the mitogenome is A (39.27%), G
      (7.71%), C (12.01%), and T (41.01%). Its gene order and content are identical to
      the common type found in most insect mitogenomes. All protein coding genes (PCGs)
      start with a typical ATN initiation codon, except for the cox1 gene, which begins
      with TTAG codon. Nine genes used standard complete termination codon TAA, whereas
      the cox1, cox2, nad3, and nad5 genes end with single T. All tRNAs display typical
      secondary cloverleaf structures as those of other insects. Additionally, the 552
      bp long AT-rich region contained several structures common to the other
      lepidopterons, such as some structures of repeated motifs and microsatellite-like
      elements. Phylogenetic analysis showed that the Antheraea pernyi Yu6 was close to
      Saturniidae.

PMID- 25939049
TI  - The complete mitochondrial genome of Antheraea pernyi strain 731 (Lepidoptera:
      Saturniidae).
AB  - In this study, the complete mitochondrial genome of Antheraea pernyi strain 731
      (Lepidoptera: Saturniidae) is determined for the first time. It is a circular
      molecule of 15,570 bp in length, with 37 typical coding genes and one non-coding
      A T-rich region. Its gene order and content are identical to the common type
      found in most insect mitogenomes. All protein-coding genes (PCGs) start with a
      typical ATN initiation codon, except for the cox1 gene, which begins with TTAG
      codon. Nine genes used standard complete termination codon TAA, whereas the cox1,
      cox2, nad3, and nad5 genes end with single T. All tRNAs display typical secondary
      cloverleaf structures as those of other insects. Additionally, the non-coding AT
      rich region is 553 bp long, located between rrnS and trnM genes. It contains some
      structures of repeated motifs and microsatellite-like elements characteristic of
      the other lepidopterons. Phylogenetic analysis showed that the Antheraea pernyi
      731 was close to Saturniidae.

PMID- 25939050
TI  - Artificial chaperones based on mixed shell polymeric micelles: insight into the
      mechanism of the interaction of the chaperone with substrate proteins using
      Forster resonance energy transfer.
AB  - Controlled and reversible interactions between polymeric nanoparticles and
      proteins have gained more and more attention with the hope to address many
      biological issues such as prevention of protein denaturation, interference of the
      fibrillation of disease relative proteins, removing of toxic biomolecules as well
      as targeting delivery of proteins, etc. In such cases, proper analytic techniques
      are needed to reveal the underlying mechanism of the particle-protein
      interactions. In the current work, Forster Resonance Energy Transfer (FRET) was
      used to investigate the interaction of our tailor designed artificial chaperone
      based on mixed shell polymeric micelles (MSPMs) with their substrate proteins. We
      designed a new kind of MSPMs with fluorescent acceptors precisely placed at the
      desired locations as well as hydrophobic domains which can adsorb unfolded
      proteins with a propensity to aggregate. Interactions of such model micelles with
      a donor-labeled protein-FITC-lysozyme, was monitored by FRET. The fabrication
      strategy of MSPMs makes it possible to control the accurate location of the
      acceptor, which is critical to reveal some unexpected insights of the micelle
      protein interactions upon heating and cooling. Preadsorption of native proteins
      onto the hydrophobic domains of the MSPMs is a key step to prevent thermo
      denaturation by diminishing interprotein aggregations. Reversible protein
      adsorption during heating and releasing during cooling have been confirmed.
      Conclusions from the FRET effect are in line with the measurement of residual
      enzymatic activity. 

PMID- 25939051
TI  - Visualization of Streptococcus pneumoniae within Cardiac Microlesions and
      Subsequent Cardiac Remodeling.
AB  - During bacteremia Streptococcus pneumoniae can translocate across the vascular
      endothelium into the myocardium and form discrete bacteria-filled microscopic
      lesions (microlesions) that are remarkable due to the absence of infiltrating
      immune cells. Due to their release of cardiotoxic products, S. pneumoniae within
      microlesions are thought to contribute to the heart failure that is frequently
      observed during fulminate invasive pneumococcal disease in adults. Herein is
      demonstrated a protocol for experimental mouse infection that leads to
      reproducible cardiac microlesion formation within 30 hr. Instruction is provided
      on microlesion identification in hematoxylin & eosin stained heart sections and
      the morphological distinctions between early and late microlesions are
      highlighted. Instruction is provided on a protocol for verification of S.
      pneumoniae within microlesions using antibodies against pneumococcal capsular
      polysaccharide and immunofluorescent microscopy. Last, a protocol for antibiotic
      intervention that rescues infected mice and for the detection and assessment of
      scar formation in the hearts of convalescent mice is provided. Together, these
      protocols will facilitate the investigation of the molecular mechanisms
      underlying pneumococcal cardiac invasion, cardiomyocyte death, cardiac remodeling
      as a result of exposure to S. pneumoniae, and the immune response to the
      pneumococci in the heart. 

PMID- 25939052
TI  - Alignment of Next-Generation Sequencing Reads.
AB  - High-throughput DNA sequencing has considerably changed the possibilities for
      conducting biomedical research by measuring billions of short DNA or RNA
      fragments. A central computational problem, and for many applications a first
      step, consists of determining where the fragments came from in the original
      genome. In this article, we review the main techniques for generating the
      fragments, the main applications, and the main algorithmic ideas for computing a
      solution to the read alignment problem. In addition, we describe pitfalls and
      difficulties connected to determining the correct positions of reads. 

PMID- 25939053
TI  - A Mathematician's Odyssey.
AB  - In this overview of my research, I have aimed to give the background as to how I
      came to be involved in my various areas of interest, with an emphasis on the
      early phases of my career, which largely determined my future directions. I had
      the enormous good fortune to have worked under two of the most outstanding
      scientists of the twentieth century, R.A. Fisher and Joshua Lederberg. From
      mathematics and statistics, I went to population genetics and the early use of
      computers for modeling and simulation. Molecular biology took me into the
      laboratory and eventually to somatic cell genetics and human gene mapping. One
      chance encounter led me into the HLA field and another led me into research on
      cancer, especially colorectal cancer. On the way, I became a champion of the
      Human Genome Project and of the need for scientists to help promote the public
      understanding of science. 

PMID- 25939054
TI  - Mendelian Randomization: New Applications in the Coming Age of Hypothesis-Free
      Causality.
AB  - Mendelian randomization (MR) is an approach that uses genetic variants associated
      with a modifiable exposure or biological intermediate to estimate the causal
      relationship between these variables and a medically relevant outcome. Although
      it was initially developed to examine the relationship between modifiable
      exposures/biomarkers and disease, its use has expanded to encompass applications
      in molecular epidemiology, systems biology, pharmacogenomics, and many other
      areas. The purpose of this review is to introduce MR, the principles behind the
      approach, and its limitations. We consider some of the new applications of the
      methodology, including informing drug development, and comment on some promising
      extensions, including two-step, two-sample, and bidirectional MR. We show how
      these new methods can be combined to efficiently examine causality in complex
      biological networks and provide a new framework to data mine high-dimensional
      studies as we transition into the age of hypothesis-free causality. 

PMID- 25939056
TI  - The Theory and Practice of Genome Sequence Assembly.
AB  - The current genomic revolution was made possible by joint advances in genome
      sequencing technologies and computational approaches for analyzing sequence data.
      The close interaction between biologists and computational scientists is perhaps
      most apparent in the development of approaches for sequencing entire genomes, a
      feat that would not be possible without sophisticated computational tools called
      genome assemblers (short for genome sequence assemblers). Here, we survey the key
      developments in algorithms for assembling genome sequences since the development
      of the first DNA sequencing methods more than 35 years ago. 

PMID- 25939057
TI  - Large Frequency Change with Thickness in Interlayer Breathing Mode--Significant
      Interlayer Interactions in Few Layer Black Phosphorus.
AB  - Bulk black phosphorus (BP) consists of puckered layers of phosphorus atoms. Few
      layer BP, obtained from bulk BP by exfoliation, is an emerging candidate as a
      channel material in post-silicon electronics. A deep understanding of its
      physical properties and its full range of applications are still being uncovered.
      In this paper, we present a theoretical and experimental investigation of phonon
      properties in few-layer BP, focusing on the low-frequency regime corresponding to
      interlayer vibrational modes. We show that the interlayer breathing mode A(3)g
      shows a large redshift with increasing thickness; the experimental and
      theoretical results agree well. This thickness dependence is two times larger
      than that in the chalcogenide materials, such as few-layer MoS2 and WSe2, because
      of the significantly larger interlayer force constant and smaller atomic mass in
      BP. The derived interlayer out-of-plane force constant is about 50% larger than
      that of graphene and MoS2. We show that this large interlayer force constant
      arises from the sizable covalent interaction between phosphorus atoms in adjacent
      layers and that interlayer interactions are not merely of the weak van der Waals
      type. These significant interlayer interactions are consistent with the known
      surface reactivity of BP and have been shown to be important for electric-field
      induced formation of Dirac cones in thin film BP. 

PMID- 25939058
TI  - Low-pH Solid-Phase Amino Labeling of Complex Peptide Digests with TMTs Improves
      Peptide Identification Rates for Multiplexed Global Phosphopeptide Analysis.
AB  - We present a novel tandem mass tag solid-phase amino labeling (TMT-SPAL) protocol
      using reversible immobilization of peptides onto octadecyl-derivatized (C18)
      solid supports. This method can reduce the number of steps required in complex
      protocols, saving time and potentially reducing sample loss. In our global
      phosphopeptide profiling workflow (SysQuant), we can cut 24 h from the protocol
      while increasing peptide identifications (20%) and reducing side reactions. Solid
      phase labeling with TMTs does require some modification to typical labeling
      conditions, particularly pH. It has been found that complete labeling equivalent
      to standard basic pH solution-phase labeling for small and large samples can be
      achieved on C18 resins under slightly acidic buffer conditions. Improved labeling
      behavior on C18 compared to that with standard basic pH solution-phase labeling
      is demonstrated. We analyzed our samples for histidine, serine, threonine, and
      tyrosine labeling to determine the degree of overlabeling and observed higher
      than expected levels (25% of all peptide spectral matches (PSMs)) of overlabeling
      at all of these amino acids (predominantly at tyrosine and serine) in our
      standard solution-phase labeling protocol. Overlabeling at all of these sites is
      greatly reduced (4-fold, to 7% of all PSMs) by the low-pH conditions used in the
      TMT-SPAL protocol. Overlabeling seems to represent a so-far overlooked mechanism
      causing reductions in peptide identification rates with NHS-activated TMT
      labeling compared to that with label-free methods. Our results also highlight the
      importance of searching data for overlabeling when labeling methods are used. 

PMID- 25939059
TI  - Lariat-Small Step or Giant Leap?

PMID- 25939055
TI  - Advances in Skeletal Dysplasia Genetics.
AB  - Skeletal dysplasias result from disruptions in normal skeletal growth and
      development and are a major contributor to severe short stature. They occur in
      approximately 1/5,000 births, and some are lethal. Since the most recent
      publication of the Nosology and Classification of Genetic Skeletal Disorders,
      genetic causes of 56 skeletal disorders have been uncovered. This remarkable rate
      of discovery is largely due to the expanded use of high-throughput genomic
      technologies. In this review, we discuss these recent discoveries and our
      understanding of the molecular mechanisms behind these skeletal dysplasia
      phenotypes. We also cover potential therapies, unusual genetic mechanisms, and
      novel skeletal syndromes both with and without known genetic causes. The
      acceleration of skeletal dysplasia genetics is truly spectacular, and these
      advances hold great promise for diagnostics, risk prediction, and therapeutic
      design. 

PMID- 25939060
TI  - A small linear peptide encompassing the NGF N-terminus partly mimics the
      biological activities of the entire neurotrophin in PC12 cells.
AB  - Ever since the discovery of its neurite growth promoting activity in sympathetic
      and sensory ganglia, nerve growth factor (NGF) became the prototype of the large
      family of neurotrophins. The use of primary cultures and clonal cell lines has
      revealed several distinct actions of NGF and other neurotrophins. Among several
      models of NGF activity, the clonal cell line PC12 is the most widely employed.
      Thus, in the presence of NGF, through the activation of the transmembrane protein
      TrkA, these cells undergo a progressive mitotic arrest and start to grow
      electrically excitable neuritis. A vast number of studies opened intriguing
      aspects of NGF mechanisms of action, its biological properties, and potential use
      as therapeutic agents. In this context, identifying and utilizing small portions
      of NGF is of great interest and involves several human diseases including
      Alzheimer's disease. Here we report the specific action of the peptide
      encompassing the 1-14 sequence of the human NGF (NGF(1-14)), identified on the
      basis of scattered indications present in literature. The biological activity of
      NGF(1-14) was tested on PC12 cells, and its binding with TrkA was predicted by
      means of a computational approach. NGF(1-14) does not elicit the neurite
      outgrowth promoting activity, typical of the whole protein, and it only has a
      moderate action on PC12 proliferation. However, this peptide exerts, in a dose
      and time dependent fashion, an effective and specific NGF-like action on some
      highly conserved and biologically crucial intermediates of its intracellular
      targets such as Akt and CREB. These findings indicate that not all TrkA pathways
      must be at all times operative, and open the possibility of testing each of them
      in relation with specific NGF needs, biological actions, and potential
      therapeutic use. 

PMID- 25939061
TI  - Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell
      lung cancer harboring EGFR T790M.
AB  - Here we studied cell-free plasma DNA (cfDNA) collected from subjects with
      advanced lung cancer whose tumors had developed resistance to the epidermal
      growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) AZD9291. We first
      performed next-generation sequencing of cfDNA from seven subjects and detected an
      acquired EGFR C797S mutation in one; expression of this mutant EGFR construct in
      a cell line rendered it resistant to AZD9291. We then performed droplet digital
      PCR on serial cfDNA specimens collected from 15 AZD9291-treated subjects. All
      were positive for the T790M mutation before treatment, but upon developing
      AZD9291 resistance three molecular subtypes emerged: six cases acquired the C797S
      mutation, five cases maintained the T790M mutation but did not acquire the C797S
      mutation and four cases lost the T790M mutation despite the presence of the
      underlying EGFR activating mutation. Our findings provide insight into the
      diversity of mechanisms through which tumors acquire resistance to AZD9291 and
      highlight the need for therapies that are able to overcome resistance mediated by
      the EGFR C797S mutation. 

PMID- 25939062
TI  - Functionally defined therapeutic targets in diffuse intrinsic pontine glioma.
AB  - Diffuse intrinsic pontine glioma (DIPG) is a fatal childhood cancer. We performed
      a chemical screen in patient-derived DIPG cultures along with RNA-seq analyses
      and integrated computational modeling to identify potentially effective
      therapeutic strategies. The multi-histone deacetylase inhibitor panobinostat
      demonstrated therapeutic efficacy both in vitro and in DIPG orthotopic xenograft
      models. Combination testing of panobinostat and the histone demethylase inhibitor
      GSK-J4 revealed that the two had synergistic effects. Together, these data
      suggest a promising therapeutic strategy for DIPG. 

PMID- 25939063
TI  - 4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of
      chimeric antigen receptors.
AB  - Chimeric antigen receptors (CARs) targeting CD19 have mediated dramatic antitumor
      responses in hematologic malignancies, but tumor regression has rarely occurred
      using CARs targeting other antigens. It remains unknown whether the impressive
      effects of CD19 CARs relate to greater susceptibility of hematologic malignancies
      to CAR therapies, or superior functionality of the CD19 CAR itself. We show that
      tonic CAR CD3-zeta phosphorylation, triggered by antigen-independent clustering
      of CAR single-chain variable fragments, can induce early exhaustion of CAR T
      cells that limits antitumor efficacy. Such activation is present to varying
      degrees in all CARs studied, except the highly effective CD19 CAR. We further
      determine that CD28 costimulation augments, whereas 4-1BB costimulation reduces,
      exhaustion induced by persistent CAR signaling. Our results provide biological
      explanations for the antitumor effects of CD19 CARs and for the observations that
      CD19 CAR T cells incorporating the 4-1BB costimulatory domain are more persistent
      than those incorporating CD28 in clinical trials. 

PMID- 25939064
TI  - Irf5 deficiency in macrophages promotes beneficial adipose tissue expansion and
      insulin sensitivity during obesity.
AB  - Accumulation of visceral adipose tissue correlates with elevated inflammation and
      increased risk of metabolic diseases. However, little is known about the
      molecular mechanisms that control its pathological expansion. Transcription
      factor interferon regulatory factor 5 (IRF5) has been implicated in polarizing
      macrophages towards an inflammatory phenotype. Here we demonstrate that mice
      lacking Irf5, when placed on a high-fat diet, show no difference in the growth of
      their epididymal white adipose tissue (epiWAT) but they show expansion of their
      subcutaneous white adipose tissue, as compared to wild-type (WT) mice on the same
      diet. EpiWAT from Irf5-deficient mice is marked by accumulation of alternatively
      activated macrophages, higher collagen deposition that restricts adipocyte size,
      and enhanced insulin sensitivity compared to epiWAT from WT mice. In obese
      individuals, IRF5 expression is negatively associated with insulin sensitivity
      and collagen deposition in visceral adipose tissue. Genome-wide analysis of gene
      expression in adipose tissue macrophages highlights the transforming growth
      factor beta1 (TGFB1) gene itself as a direct target of IRF5-mediated inhibition.
      This study uncovers a new function for IRF5 in controlling the relative mass of
      different adipose tissue depots and thus insulin sensitivity in obesity, and it
      suggests that inhibition of IRF5 may promote a healthy metabolic state during
      this condition. 

PMID- 25939065
TI  - HIV suppression by host restriction factors and viral immune evasion.
AB  - Antiviral restriction factors are an integral part of the host innate immune
      system that protects cells from viral pathogens, such as human immunodeficiency
      virus (HIV). Studies of the interactions between restriction factors and HIV have
      greatly advanced our understanding of both the viral life cycle and basic cell
      biology, as well as provided new opportunities for therapeutic intervention of
      viral infection. Here we review the recent developments towards establishing the
      structural and biochemical bases of HIV inhibition by, and viral countermeasures
      of, the restriction factors TRIM5, MxB, APOBEC3, SAMHD1, and BST2/tetherin. 

PMID- 25939066
TI  - Establishment of the National Pregnancy Registry for Atypical Antipsychotics.
AB  - OBJECTIVE: Atypical antipsychotics are widely used by reproductive-age women to
      treat a spectrum of psychiatric illnesses. Despite widespread use of this class
      of agents in women of childbearing potential, reproductive safety data across
      these medicines remain limited. The National Pregnancy Registry for Atypical
      Antipsychotics (NPRAA) at Massachusetts General Hospital was established in 2008
      to address this knowledge gap. METHOD: Data are prospectively collected from
      pregnant women, ages 18-45 years, using 3 phone interviews conducted at the
      following times: (1) proximate to the time of enrollment, (2) 7 months'
      gestation, and (3) 2-3 months postpartum. Subjects include pregnant women with
      histories of fetal exposure to second-generation antipsychotics and a comparison
      group of nonexposed pregnant women. Medical record release authorization is
      obtained for obstetric, labor and delivery, and newborn pediatric (up to 6 months
      of age) records. Information regarding the presence of major malformations is
      abstracted from the medical records along with other data regarding neonatal and
      maternal health outcomes. Identified cases of congenital malformations are sent
      to a dysmorphologist blinded to drug exposure for final adjudication. RESULTS: As
      of May 2014, 428 subjects have enrolled in the NPRAA. Efforts continue to
      increase enrollment for the purpose of enhancing the capacity to define risk
      estimates of in utero exposure to atypical antipsychotics. CONCLUSIONS: The NPRAA
      gathers prospective data regarding risk for critical outcomes following use of
      atypical antipsychotics during pregnancy. The NPRAA offers a systematic way to
      collect reproductive safety information that informs the care of women who use
      these agents to sustain psychiatric well-being. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT01246765.

PMID- 25939067
TI  - Riluzole as a neuroprotective drug for spinal cord injury: from bench to bedside.
AB  - Spinal cord injury (SCI) is a devastating event resulting in permanent loss of
      neurological function. To date, effective therapies for SCI have not been
      established. With recent progress in neurobiology, however, there is hope that
      drug administration could improve outcomes after SCI. Riluzole is a benzothiazole
      anticonvulsant with neuroprotective effects. It has been approved by the U.S.
      Food and Drug Administration as a safe and well-tolerated treatment for patients
      with amyotrophic lateral sclerosis. The mechanism of action of riluzole involves
      the inhibition of pathologic glutamatergic transmission in synapses of neurons
      via sodium channel blockade. There is convincing evidence that riluzole
      diminishes neurological tissue destruction and promotes functional recovery in
      animal SCI models. Based on these results, a phase I/IIa clinical trial with
      riluzole was conducted for patients with SCI between 2010 and 2011. This trial
      demonstrated significant improvement in neurological outcomes and showed it to be
      a safe drug with no serious adverse effects. Currently, an international, multi
      center clinical trial (Riluzole in Acute Spinal Cord Injury Study: RISCIS) in
      phase II/III is in progress with riluzole for patients with SCI
      (clinicaltrials.gov, registration number NCT01597518). This article reviews the
      pharmacology and neuroprotective mechanisms of riluzole, and focuses on existing
      preclinical evidence, and emerging clinical data in the treatment of SCI. 

PMID- 25939069
TI  - Gd-Complexes of New Arylpiperazinyl Conjugates of DTPA-Bis(amides): Synthesis,
      Characterization and Magnetic Relaxation Properties.
AB  - Two new DTPA-bis(amide) based ligands conjugated with the arylpiperazinyl moiety
      were synthesized and subsequently transformed into their corresponding Gd(III)
      complexes 1 and 2 of the type [Gd(L)H2O].nH2O. The relaxivity (R1) of these
      complexes was measured, which turned out to be comparable with that of
      Omniscan(r), a commercially available MRI contrast agent. The cytotoxicity
      studies of these complexes indicated that they are non-toxic, which reveals their
      potential and physiological suitability as MRI contrast agents. All the
      synthesized ligands and complexes were characterized with the aid of analytical
      and spectroscopic methods, including elemental analysis, 1H-NMR, FT-IR, XPS and
      fast atom bombardment (FAB) mass spectrometry. 

PMID- 25939068
TI  - Development of a novel antimicrobial screening system targeting the pyoverdine
      mediated iron acquisition system and xenobiotic efflux pumps.
AB  - The iron acquisition systems in Pseudomonas aeruginosa are inducible in response
      to low-iron conditions and important for growth of this organism under iron
      limitation. OprM is the essential outer membrane subunit of the MexAB-OprM
      xenobiotic efflux pump. We designed and constructed a new model antimicrobial
      screening system targeting both the iron-uptake system and xenobiotic efflux
      pumps. The oprM gene was placed immediately downstream of the ferri-pyoverdine
      receptor gene, fpvA, in the host lacking chromosomal oprM and the expression of
      oprM was monitored by an antibiotic susceptibility test under iron depleted and
      replete conditions. The recombinant cells showed wild-type susceptibility to pump
      substrate antibiotics, e.g., aztreonam, under iron limitation and became
      supersusceptible to them under iron repletion, suggesting that expression of oprM
      is under control of the iron acquisition system. Upon screening of a chemical
      library comprising 2952 compounds using this strain, a compound-ethyl 2-(1
      acetylpiperidine-4-carboxamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate
      was found to enhance the efficacy of aztreonam under iron limitation, suggesting
      that the compound inhibits either the iron acquisition system or the MexAB-OprM
      efflux pump. This compound was subsequently found to inhibit the growth of wild
      type cells in the presence of sublethal amounts of aztreonam, regardless of the
      presence or absence of dipyridyl, an iron-chelator. The compound was eventually
      identified to block the function of the MexAB-OprM efflux pump, showing the
      validity of this new method. 

PMID- 25939070
TI  - Regulated deficit irrigation alters anthocyanins, tannins and sensory properties
      of cabernet sauvignon grapes and wines.
AB  - Four regulated deficit irrigation (RDI) regimes were applied to Cabernet
      Sauvignon grapes, which were analyzed for phenolics and also made into wine over
      three consecutive growing seasons. Relative to an industry standard regime (IS),
      yield was reduced over the three years by 37% in a full-deficit (FD) regime and
      by 18% in an early deficit (ED) regime, whereas no yield reduction occurred with
      a late deficit (LD) regime. Relative to IS, skin anthocyanin concentration (fresh
      weight basis) was 18% and 24% higher in ED and FD, respectively, whereas no
      effect was seen in LD. Seed tannin concentration was 3% and 8% higher in ED and
      FD, respectively, relative to the other two RDI regimes, whereas seed tannin
      content (amount per berry) was higher in IS than in FD. There were no practically
      relevant effects on the basic chemistry of the wines. The finished wines showed
      concentrations of tannins and anthocyanins that generally mirrored observed
      differences in skin and seed phenolic concentrations, although these were
      amplified in FD wines. Descriptive sensory analysis of the 2008 wines showed that
      FD wines were the most saturated in color, with higher purple hue, roughness,
      dryness and harshness, followed by ED wines, whereas IS and LD wines were less
      saturated in color and with higher brown and red hues. Overall, FD and ED seemed
      to yield fruit and wine with greater concentrations of phenolics than IS and LD,
      with the additional advantage of reducing water usage. However, these apparent
      benefits need to be balanced out with reductions in crop yields and potential
      long-term effects associated with pre-veraison water deficits. 

PMID- 25939071
TI  - Potential grape-derived contributions to volatile ester concentrations in wine.
AB  - Grape composition affects wine flavour and aroma not only through varietal
      compounds, but also by influencing the production of volatile compounds by yeast.
      C9 and C12 compounds that potentially influence ethyl ester synthesis during
      fermentation were studied using a model grape juice medium. It was shown that the
      addition of free fatty acids, their methyl esters or acyl-carnitine and acyl
      amino acid conjugates can increase ethyl ester production in fermentations. The
      stimulation of ethyl ester production above that of the control was apparent when
      lower concentrations of the C9 compounds were added to the model musts compared
      to the C12 compounds. Four amino acids, which are involved in CoA biosynthesis,
      were also added to model grape juice medium in the absence of pantothenate to
      test their ability to influence ethyl and acetate ester production. beta-Alanine
      was the only one shown to increase the production of ethyl esters, free fatty
      acids and acetate esters. The addition of 1 mg?L(-1) beta-alanine was enough to
      stimulate production of these compounds and addition of up to 100 mg?L(-1) beta
      alanine had no greater effect. The endogenous concentrations of beta-alanine in
      fifty Cabernet Sauvignon grape samples exceeded the 1 mg?L(-1) required for the
      stimulatory effect on ethyl and acetate ester production observed in this study.

PMID- 25939072
TI  - Doubt, defiance, and identity: Understanding resistance to male circumcision for
      HIV prevention in Malawi.
AB  - Global policy recommendations to scale up of male circumcision (MC) for HIV
      prevention tend to frame the procedure as a simple and efficacious public health
      intervention. However, there has been variable uptake of MC in countries with
      significant HIV epidemics. Kenya, for example, has embraced MC and has been
      dubbed a 'leader' by the global health community, while Malawi has been branded a
      'laggard' in its slow adoption of a national programme, with a strong political
      discourse of resistance forming around MC. Regardless of any epidemiological or
      technical evidence, the uptake of international recommendations will be shaped by
      how a policy, and the specific artefacts that constitute that policy, intersect
      with local concerns. MC holds particular significance within many ethnic and
      religious groups, serving as an important rite of passage, but also designating
      otherness or enabling the identification of the social and political self.
      Understanding how the artefact of MC intersects with local social, economic, and
      political contexts, is therefore essential to understand the acceptance or
      resistance of global policy recommendations. In this paper we present an in-depth
      analysis of Malawi's political resistance to MC, finding that ethnic and
      religious divisions dominating recent political movements aligned well with
      differing circumcision practices. Political resistance was further found to
      manifest through two key narratives: a 'narrative of defiance' around the need to
      resist donor manipulation, and a 'narrative of doubt' which seized on a piece of
      epidemiological evidence to refute global claims of efficacy. Further, we found
      that discussions over MC served as an additional arena through which ethnic
      identities and claims to power could themselves be negotiated, and therefore used
      to support claims of political legitimacy. 

PMID- 25939073
TI  - Neighbourhood vitality and physical activity among the elderly: The role of
      walkable environments on active ageing in Barcelona, Spain.
AB  - This study investigated whether neighbourhood vitality and walkability were
      associated with active ageing of the elderly. Immobility, activity engagement and
      physical activity were explored in relation with age, gender and walkability of
      the built environment. Number of trips per day and minutes spent on walking by
      the elderly were extracted from a broad travel survey with more than 12,000 CATI
      interviews and were compared across vital and non-vital urban environments.
      Results highlight the importance of vital environments for elderly active
      mobility as subpopulations residing in highly walkable neighbourhoods undertook
      more trips and spent more minutes walking than their counterparts. The results
      also suggest that the built environment has different effects in terms of gender,
      as elderly men were more susceptible to urban vitality than elderly women. 

PMID- 25939074
TI  - Inclusive public participation in health: Policy, practice and theoretical
      contributions to promote the involvement of marginalised groups in healthcare.
AB  - Migrants and ethnic minorities are under-represented in spaces created to give
      citizens voice in healthcare governance. Excluding minority groups from the
      health participatory sphere may weaken the transformative potential of public
      participation, (re)producing health inequities. Yet few studies have focused on
      what enables involvement of marginalised groups in participatory spaces. This
      paper addresses this issue, using the Participation Chain Model (PCM) as a
      conceptual framework, and drawing on a case study of user participation in a
      Dutch mental health advocacy project involving Cape Verdean migrants. Data
      collection entailed observation, documentary evidence and interviews with Cape
      Verdeans affected by psychosocial problems (n = 20) and institutional
      stakeholders (n = 30). We offer practice, policy and theoretical contributions.
      Practically, we highlight the importance of a proactive approach providing
      minorities and other marginalised groups with opportunities and incentives that
      attract, retain and enable them to build and release capacity through
      involvement. In policy terms, we suggest that both health authorities and civil
      society organisations have a role in creating 'hybrid' spaces that promote the
      substantive inclusion of marginalised groups in healthcare decision-making.
      Theoretically, we highlight shortcomings of PCM and its conceptualisation of
      users' resources, suggesting adaptations to improve its conceptual and practical
      utility. 

PMID- 25939075
TI  - Increased incidence of coronary heart disease associated with "double burden" in
      a cohort of Italian women.
AB  - Objective of this study was to assess the risk of coronary heart disease (CHD)
      associated with the combination of employment status and child care among women
      of working age, also examining the sex of the offspring. Only two previous
      studies investigated the effect of double burden on CHD, observing an increased
      risk among employed women with high domestic burden or providing child care,
      although the relative risks were marginally or not significant. The study
      population was composed of all women 25-50 years old at 2001 census, living in
      Turin in families composed only by individuals or couples, with or without
      children (N = 109,358). Subjects were followed up during 2002-2010 for CHD
      incidence and mortality through record-linkage of the cohort with the local
      archives of mortality and hospital admissions. CHD risk was estimated by
      multivariate Poisson regression models. Among employed women, CHD risk increased
      significantly by 29% for each child in the household (IRR = 1.29) and by 39% for
      each son (IRR = 1.39), whereas no association with the presence of children was
      found among non-employed women or among employed women with daughters. When
      categorized, the presence of two or more sons significantly increased CHD risk
      among employed women (IRR = 2.23), compared to those without children. The study
      found a significant increase in CHD risk associated with the presence of two or
      more sons in the household, but not daughters, among employed women. This is a
      new finding, which should be confirmed in other studies, conducted also in
      countries where the division of domestic duties between males and females is more
      balanced, such as the European Nordic countries. 

PMID- 25939076
TI  - [Souls without a Home: The Situation of Asylum Seekers in Germany].

PMID- 25939077
TI  - [Dementia Wards are not a Useful Specialisation--Pro].

PMID- 25939078
TI  - [Dementia Wards are not a Useful Specialisation--Contra].

PMID- 25939079
TI  - [Which factors predict treatment duration and outcome of psychotherapeutic
      hospital treatment?].
AB  - OBJECTIVE: Several studies document the effectiveness of psychotherapeutic
      hospital treatment in German speaking countries, although results show a
      considerable heterogeneity. METHODS: Based on data from a comprehensive meta
      analysis, we investigated the impact of potential study-level predictors on
      average treatment duration and average symptom severity at discharge using meta
      regression. RESULTS: Selected predictors explain 55 and 78 percent of between
      study variance of mean treatment duration and mean symptom severity at discharge,
      respectively. Samples of younger patients, samples including more patients with
      personality disorders, samples treated in specialist centers and samples from
      older investigations showed longer average treatment durations. Studies in
      patient populations with less severe symptoms at intake and a lower proportion of
      personality disorders showed lower impairment at discharge. We found a
      statistically significant positive association between severity of symptoms at
      discharge and treatment duration. CONCLUSION: Regarding the higher symptom load
      at discharge in patients with higher impairment at intake and personality
      disorders, treatment concepts for these groups require improvement, for example
      through flexible treatment durations.

PMID- 25939082
TI  - Long-Term Retrospective Clinical and Radiographic Follow-up of 205 Branemark
      System Mk III TiUnite Implants Submitted to Either Immediate or Delayed Loading.
AB  - BACKGROUND: Studies are needed to evaluate long-term performance of immediately
      loaded implants with moderately rough surface. This retrospective study evaluated
      long-term survival and periimplant soft and hard tissue conditions in patients
      treated with TiUnite implants. MATERIALS AND METHODS: Forty-one consecutive
      patients (mean age, 52.6 years) received 205 Branemark System Mk III TiUnite
      implants (145 maxillary, 60 mandibular). The indication was single tooth (n = 7
      implants), partial (n = 94), or full arches (n = 104). One hundred thirteen
      implants were immediately loaded. Cumulative survival rate (CSR) of implants was
      assessed. Long-term marginal bone remodeling, probing pocket depth (PPD), and
      periimplant mucosa conditions were assessed. RESULTS: Follow-up averaged 8.8
      years (range, 6.6-10.6 years). Eight implants in 5 patients failed. CSR was 96.1%
      (implant basis) and 87.8% (patient basis) up to 10 years. At the longest follow
      up, bone loss averaged 0.43 +/- 1.15 mm (n = 173), PPD averaged 3.64 +/- 0.74 mm,
      and periimplant mucosa was healthy in 74.6% of cases. Furthermore, 50.3% and
      35.5% of implants scored negative for plaque and bleeding, respectively. No
      significant difference in CSR and hard and soft tissue conditions was found in
      the long term between immediately and delayed loaded implants. CONCLUSION:
      Implants with TiUnite surface demonstrated excellent long-term survival, marginal
      bone response, and soft tissue conditions, despite a nonoptimal level of oral
      hygiene.

PMID- 25939083
TI  - Effect of Implant Thread Geometry on Secondary Stability, Bone Density, and Bone
      to-Implant Contact: A Biomechanical and Histological Analysis.
AB  - PURPOSE: This study evaluated the effect of 2 different thread designs on
      secondary stability (micromotion) and osseointegration rate in dense and
      cancellous bones. MATERIALS AND METHODS: Forty large threaded and 40 small
      threaded implants (Cortex) were placed in low- (iliac crest) and high-density
      (mandible) bone of sheep. Two months later, micromobility tests and histological
      analysis were performed to measure secondary stability, osseointegration (bone-to
      implant contact percentage [%BIC]), and bone density (bone volume percentage
      [%BV]). The value of actual micromotion of implant is introduced as a new
      parameter to evaluate secondary stability. RESULTS: Large threaded implants
      showed significantly higher %BIC and %BV than small threaded implants in low
      density bone and statistically higher secondary stability in cancellous and
      cortical bones. CONCLUSIONS: Implants in dense bone reach higher secondary
      stability than those in cancellous bone, despite the lower %BIC. Implant geometry
      and bone density play a key role in secondary stability. Large thread design
      improves bone anchorage mechanically and histologically as compared with small
      threaded implants.

PMID- 25939084
TI  - Robotic production of cancer cell spheroids with an aqueous two-phase system for
      drug testing.
AB  - Cancer cell spheroids present a relevant in vitro model of avascular tumors for
      anti-cancer drug testing applications. A detailed protocol for producing both
      mono-culture and co-culture spheroids in a high throughput 96-well plate format
      is described in this work. This approach utilizes an aqueous two-phase system to
      confine cells into a drop of the denser aqueous phase immersed within the second
      aqueous phase. The drop rests on the well surface and keeps cells in close
      proximity to form a single spheroid. This technology has been adapted to a
      robotic liquid handler to produce size-controlled spheroids and expedite the
      process of spheroid production for compound screening applications. Spheroids
      treated with a clinically-used drug show reduced cell viability with increase in
      the drug dose. The use of a standard micro-well plate for spheroid generation
      makes it straightforward to analyze viability of cancer cells of drug-treated
      spheroids with a micro-plate reader. This technology is straightforward to
      implement both robotically and with other liquid handling tools such as manual
      pipettes. 

PMID- 25939085
TI  - Data-fusion of high resolution X-ray CT, SEM and EDS for 3D and pseudo-3D
      chemical and structural characterization of sandstone.
AB  - When dealing with the characterization of the structure and composition of
      natural stones, problems of representativeness and choice of analysis technique
      almost always occur. Since feature-sizes are typically spread over the nanometer
      to centimeter range, there is never one single technique that allows a rapid and
      complete characterization. Over the last few decades, high resolution X-ray CT
      (MU-CT) has become an invaluable tool for the 3D characterization of many
      materials, including natural stones. This technique has many important
      advantages, but there are also some limitations, including a tradeoff between
      resolution and sample size and a lack of chemical information. For geologists,
      this chemical information is of importance for the determination of minerals
      inside samples. We suggest a workflow for the complete chemical and structural
      characterization of a representative volume of a heterogeneous geological
      material. This workflow consists of combining information derived from CT scans
      at different spatial resolutions with information from scanning electron
      microscopy and energy-dispersive X-ray spectroscopy. 

PMID- 25939086
TI  - In situ observation of carbon nanotube yarn during voltage application.
AB  - Carbon nanotube (CNT) yarns are fabricated by drawing (combined with spinning)
      from CNT forests and grown on a substrate. Three types of phenomena occur in
      these CNT yarns with increasing amounts of current: yarn rotation, catalyst
      evaporation, and breakage of the yarn. These phenomena result from the resistive
      heating occurring during the current flow, and have been observed in situ under
      vacuum by transmission electron microscopy. If these CNT yarns are applied to
      electronic circuits, the rotation and breakage may lead to circuit failure.
      However, catalyst evaporation is a useful method for purifying CNT yarns without
      additional treatments prior to yarn fabrication. 

PMID- 25939087
TI  - Quantification of fluids injection in a glass-bead matrix using X-ray
      microtomography.
AB  - Several daily activities involve the accumulation or percolation of fluids
      through porous media. X-ray microtomography is a non-invasive technique capable
      of providing images of the internal microstructure of materials showing the
      different phases of fluid distribution present in the sample directly or at the
      pore-scale. This methodology was used to qualitatively and quantitatively assess
      samples consisting with glass beads of standard size, which contained fluid
      filling a porous region. Three samples were prepared with 0.6 mm or 0.8 mm
      diameter glass beads inserted into a glass tube with an inner diameter of 6.7 mm
      and 1.0 mm wall thickness. The fluids injected were dopant salt-water solution,
      industrial oil and commercial oil. The samples were scanned using a Skyscan-1172
      microtomographic system. All phases present in the sample were differentiated.
      The values of injected fluids were determined through 2D and 3D analyses. Two
      types of solutions were used, one doped with KI, and the other with
      BaCl(2).(2)H(2)O. The percentage of KI used allowed the individualization of the
      solution and, therefore, the direct quantification of this phase through 2D and
      3D images.

PMID- 25939088
TI  - Immunofluorescence and ultrastructural analysis of the chromatoid body during
      spermatogenesis of Triatoma platensis and T. rubrovaria (Hemiptera, Triatominae).
AB  - This study sought to analyze spermatogenesis in two species of triatomines
      (Triatoma rubrovaria and T. platensis) by focusing on the chromatoid body (CB)
      during three stages of spermatogenesis (spermatocytogenesis, meiosis, and
      spermiogenesis). The cytochemistry technique known as silver impregnation
      revealed nucleolar persistence. We suggest that this phenomenon is fundamental to
      the formation of the CB during spermatogenesis, as it allows for the nucleolus or
      nucleolar fragments to maintain their transcriptional activity during the entire
      meiosis phase and to apply all transcribed RNA to CB formation. The
      ultrastructural analysis of T. platensis and T. rubrovaria spermatids revealed
      the presence of the nucleolus within the spermatid nucleus, as well as the CB
      near the nuclear membrane. Immunofluorescence for fibrillarin revealed the
      presence of protein in both the nucleolus and the cytoplasm of spermatogonia.
      Based on these findings, we suggest that the formation of the CB begins during
      the first phase of spermatogenesis, or spermatocytogenesis. Furthermore, we also
      observed the presence of fibrillarin protein in the CB near the elongating
      spermatids. Unlike the spermatogonia, spermatids showed no fibrillarin markings
      in the nucleolar region, a finding which is consistent with the lack of post
      meiotic transcriptional activity during triatomine spermiogenesis. Thus, this
      study suggests that the formation of the CB begins during spermatocytogenesis and
      is intensified by transcriptional activity when nucleolar persistence occurs in
      meiosis. Moreover, the findings are consistent with the absence of
      transcriptional activity in the nucleolus during spermiogenesis, and they
      demonstrate that all transcriptional activity during spermatid differentiation is
      supported by the CB. 

PMID- 25939089
TI  - Effect of experimental diabetes and insulin replacement on intestinal metabolism
      and excretion of 4-nitrophenol in rats.
AB  - Luminal appearance of 4-nitrophenol (PNP) metabolites (4-nitrophenol-beta
      glucuronide (PNP-G) and 4-nitrophenol-sulfate (PNP-S)) and activity of the
      related metabolic enzymes have been investigated in control and experimental
      diabetic rats. Experimental diabetes was induced by administration of
      streptozotocin (65 mg/kg i.v.). PNP (500 MUmol/L) was luminally perfused in the
      small intestine and the metabolites were determined in the perfusion solution.
      Effect of insulin replacement was also investigated in the diabetic rats. It was
      found that experimental diabetes increased the luminal appearance of PNP-G, which
      could be completely compensated by rapid-acting insulin administration (1 U/kg
      i.v.). Activities of the enzymes involved in PNP-G production (UDP
      glucuronyltransferase and beta-glucuronidase) were also elevated; however, these
      changes were only partially compensated by insulin. Luminal appearance of PNP-S
      was not significantly changed by administration of streptozotocin and insulin.
      Activities of the enzymes of PNP-S production (sulfotransferases and
      arylsulfatases) did not change in the diabetic rats. The results indicate that
      experimental diabetes can provoke changes in intestinal drug metabolism. It
      increased intestinal glucuronidation of PNP but did not influence sulfate
      conjugation. No direct correlation was found between the changes of metabolic
      enzyme activities and the luminal appearance of the metabolites. 

PMID- 25939090
TI  - Clinical features of delusional jealousy in elderly patients with dementia.
AB  - OBJECTIVE: Delusional jealousy is a psychotic syndrome characterized by a belief
      in the infidelity of one's spouse that reaches delusional intensity. Although
      delusional jealousy has been described in relation to organic psychosis, little
      is known concerning the actual role of delusional jealousy in dementia. The aim
      of the present study was to investigate the clinical features of delusional
      jealousy and possible mechanisms whereby delusional jealousy arises in patients
      with dementia. METHOD: We studied 208 consecutive outpatients with dementia
      (diagnosis based on DSM-III-R criteria; mean [SD] age of 77.0 [8.0] years; study
      period: September 2011-August 2012). Delusional jealousy was defined as a false
      belief derived from a pathological jealousy that makes the patient believe that
      his or her spouse is unfaithful. The prevalence of delusional jealousy was
      compared between Alzheimer's disease, dementia with Lewy bodies, and vascular
      dementia. Patients with and without delusional jealousy were compared in terms of
      general characteristics. In addition, each patient with delusional jealousy and
      their primary caregivers were interviewed about the clinical features of the
      syndrome. RESULTS: Of the 208 patients with dementia, 18 (8.7%) showed delusional
      jealousy. The prevalence of delusional jealousy in patients who had dementia with
      Lewy bodies (26.3%) was significantly higher than that in patients with
      Alzheimer's disease (5.5%) (P < .01). There were no significant differences
      between patients with and without delusional jealousy in regard to gender (P =
      1.00), age (P = .81), educational attainment (P = .29), presence of other persons
      living with the couple (P = .22), and Mini-Mental State Examination score (P =
      .47). On the other hand, delusional jealousy was preceded by the onset of serious
      physical diseases in nearly half of the patients. Delusional jealousy resolved
      within 12 months after treatment in 15 of 18 patients (83%). CONCLUSIONS:
      Although delusional jealousy is a considerable problem in dementia, the prognosis
      of delusional jealousy in demented patients appears to be relatively benign. In
      dementia, delusional jealousy may develop more easily in patients who have
      dementia with Lewy bodies and those with coexisting serious physical disorders.

PMID- 25939091
TI  - Simultaneous determination of four designer drugs and their major metabolites by
      liquid chromatography-mass spectrometry.
AB  - A sensitive liquid chromatography-electrospray ionization-ion trap mass
      spectrometry (LC-ESI-ITMS) method was utilized for the simultaneous analysis of
      four designer drugs and their in vitro metabolites in rat liver microsome S9
      fraction. Four designer drugs, including methcathinone (MC), 3,4
      methylenedioxymethcathinone (MDMC), 3,4-methylenedioxy-pyrovalerone (MDPV) and 4'
      methyl-alpha-pyrrolidinopropiophenone (MPPP), were individually incubated with
      rat liver microsome S9 fraction, and the incubation mixtures were pooled together
      and analyzed by LC-ESI-ITMS simultaneously. Besides four designer drugs, five of
      their main metabolites were identified via the analysis of protonated molecules
      and tandem mass spectrometry data. Meanwhile, the quantification analysis of four
      designer drugs in rat liver microsome S9 fraction was performed, the calibration
      curves showed good linearity in the range of 0.01-5.0MUg/mL and the detection
      limits were below 0.03MUg/mL with RSDs less than 5.9% and recovery ratios above
      77.4%. The experimental results not only showed that these designer drugs could
      be easily metabolized in rat liver microsome, and also displayed the
      superiorities of the method including time and cost saving, high efficiency,
      sensitivity and selectivity. The studies in this study indicated that the
      approach could be applied in the determination of illicit drugs and their
      metabolites in medical, pharmaceutical and forensic investigations.

PMID- 25939092
TI  - Simultaneous determination of plant hormones in peach based on dispersive liquid
      liquid microextraction coupled with liquid chromatography-ion trap mass
      spectrometry.
AB  - Fruit development is influenced greatly by endogenous hormones including
      salicylic acid (SA) and abscisic acid (ABA). Mass spectrometry with high
      sensitivity has become a routine technology to analyze hormones. However,
      pretreatment of plant samples remains a difficult problem. Thus, dispersive
      liquid-liquid microextraction (DLLME) was used to concentrate trace plant
      hormones before liquid chromatography-ion trap mass spectrometry (LC-ITMS)
      analysis. Standard curves were linear within the ranges of 0.5-50, 0.2-20ng/mL
      for SA and ABA, respectively. The correlation coefficients were greater than
      0.9995 with recoveries above 87.5%. The limits of detection were 0.2ng/mL for SA
      and 0.1ng/mL for ABA in spiked water solution, respectively (injection 20MUL).
      The successful analysis of SA and ABA in fruit samples indicated our DLLME-LC
      ITMS approach was efficient, allowing reliable quantification of both two
      compounds from very small amounts of plant material. Moreover, this research
      revealed the relationship between SA and ABA content and development of peach
      fruit at different growth stages.

PMID- 25939093
TI  - Rapid determination of X-ray contrast agent iomeprol in human plasma by on-line
      solid-phase extraction coupled with phase optimized liquid chromatography.
AB  - Phase optimized liquid chromatography (POPLC) allows for the optimized
      combination of column segments of any length and stationary phases with different
      functionalities. In this study, a simple and rapid method using POPLC coupled
      with on-line solid-phase extraction (SPE) for the analysis of X-ray contrast
      media agent iomeprol (IOM) in human plasma was developed. Because the phenyl (PH)
      stationary phase has strong hydrophobic and pi-pi interactions with IOM and
      iopromide (IOP, internal standard), the best separation efficiency was achieved
      with a 250mm*3mm homogenous PH POPLC-column. Different kinds of on-line SPE
      sorbents were studied, including restricted access material-alkyl diol silica
      (ADS), LiChrolut EN with excellent absorption capacity and hydrophilic-lipophilic
      balanced Oasis HLB. The most efficient on-line sample clean-up was carried out
      using a fast-flow on-line purification approach with an Oasis HLB pre-column
      ((20mm*2mm, 30MUm). This pre-column showed excellent durability and
      reproducibility. At least 400 samples could be analyzed with one pre-column. Each
      plasma sample was directly injected and analyzed within 15min. The calibration
      curves were linear in the range of 10-1000MUg/mL. The limit of quantitation was
      2.26MUg/mL. The inter-day precision of this method was excellent and less than
      1.44%, and the intra-day precision was less than 4.44%. The inter-day and intra
      day accuracy ranged from 94.33% to 104.36% and 94.60% to 101.71%, respectively.
      This validated method is expected to be useful in the analysis of human plasma
      samples for glomerular filtration rate (GFR) measurements and assessment of
      kidney function. 

PMID- 25939094
TI  - One-step purification of R-phycoerythrin from the red edible seaweed Grateloupia
      turuturu.
AB  - A one-step chromatographic method for the purification of R-phycoerythrin (R-PE)
      of Grateloupia turuturu Yamada is described. Native R-PE was obtained with a
      purity index of 2.89 and a recovery yield of 27% using DEAE-Sepharose Fast Flow
      chromatography with a three-step increase in ionic strength. The analysis by SDS
      electrophoresis showed a broad band between 18 and 21kDa in size corresponding to
      subunits alpha and beta and a low intensity band of 29kDa corresponding to the
      gamma subunit. Two forms of R-PE were identified by gel filtration
      chromatography: a native form with a molecular weight of 260+/-5kDa and a
      dissociated form with a molecular weight of 60+/-2kDa. The native form presented
      the characteristic absorption spectrum of R-PE with three absorbance maxima at
      498, 540 and 565nm, whereas the dissociated form presented only the 498 and 540nm
      peaks. Moreover, the two forms displayed two different fluorescence maxima. 

PMID- 25939095
TI  - Simultaneous quantification of preactivated ifosfamide derivatives and of 4
      hydroxyifosfamide by high performance liquid chromatography-tandem mass
      spectrometry in mouse plasma and its application to a pharmacokinetic study.
AB  - The antitumor drug, ifosfamide (IFO), requires activation by cytochrome P450
      (CYP) to form the active metabolite, 4-hydroxyisfosfamide (4-OHIFO), leading to
      toxic by-products at high dose. In order to overcome these drawbacks,
      preactivated ifosfamide derivatives (RXIFO) were designed to release 4-OHIFO
      without CYP involvement. A high performance liquid chromatography-tandem mass
      spectrometry (HPLC-MS/MS) method was developed for the simultaneous
      quantification of 4-OHIFO, IFO and four derivatives RXIFO in mouse plasma using
      multiple reaction monitoring. Because of its instability in plasma, 4-OHIFO was
      immediately converted to the semi-carbazone derivative, 4-OHIFO-SCZ. For the six
      analytes, the calibration curves were linear from 20 to 5000ng/mL in 50MUL plasma
      and the lower limit of quantitation was determined at 20ng/mL with accuracies
      within +/-10% of nominal and precisions less than 12%. Their recoveries ranged
      from 62 to 96% by using liquid-liquid extraction. With an improved assay
      sensitivity compared to analogues, the derivative 4-OHIFO-SCZ was stable in
      plasma at 4 degrees C for 24h and at -20 degrees C for three months. For all
      compounds, the assay was validated with accuracies within +/-13% and precisions
      less than 15%. This method was applied to a comparative pharmacokinetic study of
      4-OHIFO from IFO and three derivatives RXIFO in mice. This active metabolite was
      produced by some of the novel conjugates with good pharmacokinetic properties. 

PMID- 25939096
TI  - A general separation method of phenolic acids using pH-zone-refining counter
      current chromatography and its application to oat bran.
AB  - pH-zone-refining counter-current chromatography technique for the separation of
      natural and synthetic mixtures has been widely used, especially for organic acids
      and alkaloids. Phenolic acids are very important compounds due to the potential
      treatment for a wide variety of diseases. However, there is not a general method
      for their separation. In this work, the conditions of pH-zone-refining counter
      current chromatography, involving solvent systems, concentration of retainer and
      eluter, flow rate of mobile phase as well as sample pretreatment, were optimized
      to improve extraction efficiency and reduce separation time. Finally a general
      separation method for seven common phenolic acids has been established using pH
      zone-refining counter-current chromatography. The separation of these phenolic
      acids was performed with a two-phase solvent system composed of methyl tert-butyl
      ether/acetonitrile/water at a volume ratio of 4.75: 0.25: 5, where 3mM
      trifluoroacetic acid was added to the organic stationary phase as a retainer and
      3mM NH4OH was added to the aqueous mobile phase as an eluter. As a result, seven
      phenolic acids, including syringic acid, 4-hydroxyphenylacetic acid, vanillic
      acid, caffeic acid, p-hydroxybenzoic acid, ferulic acid and p-coumaric acid were
      successfully separated with the purities of 95.9%, 67.3%, 96.9%, 82.4%, 97.0%,
      91.0%, and 97.2%, respectively. The established general method has been applied
      to the crude sample of oat bran pretreated with AB-8 resin. A total of 49.5mg of
      syringic acid, 109.2mg of p-coumaric acid and 184.5mg of ferulic acid were
      successfully purified in one run from 1.22g crude extract with the purities of
      95.2%, 93.0%, and 91.8%, respectively. 

PMID- 25939098
TI  - Living well with chronic illness: a call for public health action.

PMID- 25939099
TI  - Professionalism: a student perspective.

PMID- 25939097
TI  - Quantification of liensinine in rat plasma using ultra-performance liquid
      chromatography tandem mass spectrometry and its application to a pharmacokinetic
      study.
AB  - An ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS)
      method was developed to determine liensinine in rat plasma using carbamazepine as
      the internal standard (IS). Sample preparation was accomplished through a protein
      precipitation procedure with acetonitrile to 0.1ml plasma sample. The analyte and
      IS were separated on an Acquity UPLC BEH C18 column (2.1mm*50mm, 1.7MUm) with the
      mobile phase of acetonitrile and 0.1% formic acid in water with gradient elution
      at a flow rate of 0.40ml/min. The injection volume was 6MUl. The detection was
      performed on a triple quadrupole tandem mass spectrometer equipped with
      electrospray ionization (ESI) by multiple reactions monitoring (MRM) of the
      transitions at m/z 611.6->206.2 for liensinine and m/z 237.1->194.2 for IS. The
      linearity of this method was found to be within the concentration range of 10
      1000ng/ml with a lower limit of quantification of 10ng/ml. Only 3.0min was needed
      for an analytical run. The matrix effect was 93.8-107.4% for liensinine. The
      intra- and inter-day precision (RSD %) were less than 9.9% and accuracy (RE %)
      was within +/-10.5%. The recovery ranged from 76.2 to 86.8%. Liensinine was
      sufficiently stable under all relevant analytical conditions. The method was also
      successfully applied to the pharmacokinetic study of liensinine in rats. The
      pharmacokinetic parameters were demonstrated as followed: t1/2 was 8.2+/-3.3h,
      Cmax was 668.4+/-156.9ng/ml, and AUC0->infinity was 1802.9+/-466.4ng/mlh. 

PMID- 25939100
TI  - Not done yet: searching for the limits of patient ownership as a medical student.

PMID- 25939101
TI  - Effects of Low-Volume, High-Intensity Whole-Body Calisthenics on Army ROTC
      Cadets.
AB  - Our objective was to determine the effects of high-intensity interval training
      (HIT) on fitness in Army Reserve Officers' Training Corps cadets. Twenty-six
      college-aged (20.5 +/- 1.7 years) participants completed 4 weeks of exercise
      training 3 days . wk(-1) consisting of either approximately 60 minutes of typical
      physical training or HIT whole-body calisthenics involving 4 to 7 sets of 30
      second "all out" burpees separated by 4 minutes of active recovery. Several pre-
      and postintervention fitness variables were compared. We observed no changes
      across time or differences between groups in aerobic capacity, anaerobic
      capacity, or Army Physical Fitness Test performance (p > 0.05). However, there
      was a significant Group * Time interaction (p = 0.015) for skeletal muscle
      mitochondrial function (Tc: time constant of recovery). For the typical physical
      training group, we observed improved mitochondrial function (Tc decreased 2.4 +/-
      4.6 seconds; Cohen's d = -0.51); whereas, mitochondrial function decreased in HIT
      (Tc increased 2.4 +/- 4.6 seconds; d = 0.50). HIT sustained fitness despite the
      short duration and reduced volume of activity. A program that includes HIT as
      part of a larger program may be well suited for maintaining fitness in moderately
      trained armed forces personnel without access to equipment. 

PMID- 25939102
TI  - Air compressor battery duration with mechanical ventilation in a field anesthesia
      machine.
AB  - Compressed air to power field anesthesia machine ventilators may be supplied by
      air compressor with battery backup. This study determined the battery duration
      when the compPAC ventilator's air compressor was powered by NiCd battery to
      ventilate the Vent Aid Training Test Lung modeling high (HC = 0.100 L/cm H2O) and
      low (LC = 0.020 L/cm H2O) pulmonary compliance. Target tidal volumes (VT) were
      500, 750, and 1,000 mL. Respiratory rate = 10 bpm, inspiratory-to-expiratory time
      ratio = 1:2, and fresh gas flow = 1 L/min air. N = 5 in each group. Control
      limits were determined from the first 150 minutes of battery power for each run
      and lower control limit = mean VT - 3SD. Battery depletion occurred when VT was
      below the lower control limit. Battery duration ranged from 185.8 (+/-3.2)
      minutes in the LC-1000 group to 233.3 (+/-3.6) minutes in the HC-750 group.
      Battery duration of the LC-1000 group was less than all others (p = 0.027). The
      differences among the non-LC-1000 groups were not clinically significant. 

PMID- 25939103
TI  - Characteristics of combat-related spine injuries: a review of recent literature.
AB  - Injuries to the spinal column in combat casualties sustained during the conflicts
      in Iraq and Afghanistan are common, and the highest in reported wartime history.
      High-energy blast mechanisms from improved explosive devices have resulted in
      complex polytrauma and injury patterns, which are often markedly different from
      those injuries encountered in civilian trauma. Herein, we review the most current
      literature with regard to the distinct types of combat-related spine
      injuries/concomitant comorbidities sustained in Operations Enduring Freedom,
      Iraqi Freedom and New Dawn. 

PMID- 25939104
TI  - A descriptive study of the U.S. Marine Corps fitness tests (2000-2012).
AB  - This article describes the performance of active duty U.S. Marines on the
      Physical Fitness Test (PFT) and Combat Fitness Test (CFT) during calendar years
      2000 through 2012. Our study sample included PFT composite scores (n = 543,185),
      PFT and CFT composite scores (n = 160,936), and PFT and CFT event scores (n =
      135,926 and n = 201,953, respectively). In general, all Marines performed very
      well on each fitness test, with overall annual improvements. Interestingly, the
      majority of female Marines passed the minimum male standard on the CFT. Further
      studies will evaluate the relationship of fitness test performance and injury. 

PMID- 25939105
TI  - Evaluation of the physical activity of German soldiers depending on rank, term of
      enlistment, and task area.
AB  - Physical fitness of soldiers plays an important role during combat operations and
      training for deployment. The aim of this study was to collect data on the
      physical activity of soldiers of all rank categories and to identify task areas
      in which inactivity and the resulting health problems such as obesity,
      cardiovascular disease, and musculoskeletal problems pose a special risk. For
      this purpose, the physical activity of 169 German soldiers of different ranks and
      task areas was measured. These soldiers wore accelerometer-based physical
      activity monitors for a period of 7 days. Their activities were also documented
      in standardized forms. The results showed that officers (541 steps/h) had the
      lowest level of physical activity during their duties (compared to
      noncommissioned officers): 600 steps/h, and junior enlisted personnel: 724
      steps/h). With respect to term of enlistment, conscripts and temporary-career
      volunteers showed a higher level of physical activity than regulars (751 and 640
      vs. 539 steps/h). With respect to different task areas, drivers showed the
      highest activity level, whereas staff personnel showed the lowest. High-ranking
      personnel and soldiers in staff positions were shown to have the lowest physical
      activity level. In these groups, possible health problems caused by physical
      inactivity could be alleviated. 

PMID- 25939106
TI  - Military, demographic, and psychosocial predictors of military retention in
      enlisted army soldiers 12 months after deployment to Iraq.
AB  - OBJECTIVE: To examine military, demographic, and psychosocial predictors of
      military retention following operational deployment. METHODS: Military status 12
      months following return from Iraq deployment was assessed via service records in
      740 regular active duty Army Soldiers. Potential predictors of military retention
      were derived from prospectively administered in-person interviews and
      questionnaires conducted within 3 months following return from Iraq. RESULTS: At
      12 months following return from deployment, 18.1% (n = 134) of the sample had
      separated from military service. Cox proportional hazards analyses, adjusting for
      demographic, military, and psychosocial predictors, identified several factors
      that were independently associated with military attrition: less than (vs. equal
      to or more than) 6 years military experience (hazards ratio [HR], 3.98; 95% CI,
      2.12-7.45); unmarried (vs. married) status (HR, 1.51; 95% CI, 1.06-2.16); and
      lower (vs. higher) levels of self-reported unit support during deployment (HR,
      2.22; 95% CI, 1.42-3.47). CONCLUSIONS: Service members early in their career may
      be especially prone to military attrition. With regard to military retention, our
      findings suggest that it may be particularly important to develop initiatives
      that target organizational cohesion and support.

PMID- 25939107
TI  - Initial deployment of the 14th Parachutist Forward Surgical Team at the beginning
      of the operation Sangaris in Central African Republic.
AB  - As part of the operation Sangaris begun in December 2013 in the Central African
      Republic, the 14th Parachutist Forward Surgical Team (FST) was deployed to
      support French troops. The FST (role 2 in the NATO classification) is a mobile
      surgical-medical treatment facility. The main goal of the FST is to assure the
      initial damage control surgery and resuscitation for combat casualties, allowing
      for the early evacuation to combat support hospitals (roles 3 or 4), where
      further treatments are completed. During the first trimester of the operation
      Sangaris, 42 patients were treated at FST, of whom 29 underwent surgery. Almost
      50% of patients operated on were French servicemen. All admissions were emergency
      admissions. Orthopedic surgery represented two-thirds of surgical interventions
      executed as a result of the high proportion of limb injuries. Fifty percent of
      injuries were specifically linked to combat. Surgery in an FST is primarily
      dedicated to the treatment of combat casualties with hemorrhagic injuries, but
      additionally plays a part in supporting general medical care of French troops.
      Medical aid to the general civilian population is justifiable because of the
      presence of medical treatment facilities, even in the initial implementation of a
      military operation. 

PMID- 25939108
TI  - Health in the news: an analysis of magazines coverage of health issues in
      veterans and military service organizations.
AB  - The purpose of this study was to conduct a content analysis of Veterans and
      Military Service Organizations (VMSOs) magazines to determine what health-related
      topics VMSOs target and how they inform their constituencies about health issues.
      Health-related topics in 288 VMSOs' magazines from 21 VMSOs published in 2011 and
      2012 were coded by trained raters using a standardized manual. The top three most
      addressed health topics were Health Services (Health care, Insurance), Disability
      and Disability benefits, and post-traumatic stress disorder. Topics least
      frequently covered were Tobacco and Smoking cessation, Illegal drugs, Alcohol,
      Gulf War Syndrome, and Weight and Body composition. VMSOs are concerned about the
      health and well-being of their members given the considerable amount of content
      devoted to certain health topics such as health insurance concerns, disability,
      and post-traumatic stress disorder. However, other health concerns that affect a
      considerable number of both current military personnel and veterans and cost both
      the Department of Veterans Affairs and the Department of Defense millions
      annually, such as drug and alcohol problems, and tobacco use and smoking
      cessation, are infrequently covered. The results of this study improve our
      understanding of the health-related information that reaches the military and
      veteran populations through this important media outlet. 

PMID- 25939109
TI  - Supplemental genistein, quercetin, and resveratrol intake in active duty army
      soldiers.
AB  - Previous reports indicate that the majority of U.S. Army soldiers consume dietary
      supplements (DSs) > 1 time/wk. However, these studies did not evaluate
      phytonutrient supplementation. A growing literature suggests inclusion of
      phytonutrients in DSs may pose a risk for toxicity, which could impact the
      performance of soldier duties, as well as long-term health and wellness. This
      study was conducted to assess and understand soldiers' motivations to consume
      phytonutrient-containing DSs, specifically genistein, quercetin, and resveratrol.
      The study was a cross-sectional, descriptive mixed-methods design using a survey
      and semistructured interviews. There were 436 soldiers stationed at Joint Base
      Lewis-McChord, Washington who completed the survey, from which 36 soldiers
      completed an interview. Overall, 34% of soldiers reported taking a single or
      multicomponent phytonutrient DS > 1 time/wk, from which 41 soldiers took >1
      supplement/wk. Soldiers' reasons for use included unsure (54%), weight loss
      (12%), and other, unspecified (24%). The majority of interviewees did not consume
      DSs based on inclusion of genistein, quercetin, or resveratrol. The majority of
      soldiers, in our study, appear unable to rationalize their phytonutrient DS
      choices. Findings from this study illuminate the need for future research to
      further explore DS practices within military populations and encourage informed
      use of DSs. 

PMID- 25939110
TI  - The effects of prenatal vitamin supplementation on operationally significant
      health outcomes in female air force trainees.
AB  - OBJECTIVES: A prenatal vitamin supplementation program for female basic military
      trainees at Joint Base San Antonio-Lackland was initiated in June 2012 with the
      goals of decreasing attrition and improving performance. This project examined
      whether supplementation influences attrition rates, incidence of stress fractures
      and iron deficiency anemia, and physical performance. METHODS: This was a cohort
      based pilot study with an historical control group. Primary outcome measures
      included all-cause attrition, medical attrition, stress fractures, and iron
      deficiency anemia. RESULTS: Incidence rates of all-cause attrition, medical
      attrition, stress fractures, and anemia were similar in both groups, although the
      lower medical attrition in the supplementation group approached statistical
      significance (risk ratio, 0.74; 95% confidence interval, 0.54-1.01). CONCLUSION:
      Although this study found no statistical benefit, the operationally significant
      reduction in medical attrition of 26% suggests that providing prenatal vitamin
      supplementation to female basic trainees in the Air Force may be worthwhile.

PMID- 25939111
TI  - Evaluation of Training Methods Required for Military Women's Accurate Use of a
      Self-Diagnosis and Self-Treatment Kit for Vaginal and Urinary Symptoms.
AB  - Most military women are reluctant to attend sick call for urinary and vaginal
      symptoms during deployment; therefore, alternative self-care options are needed.
      We evaluated the type and intensity of training required for women to make
      accurate self-diagnosis and self-treatment decisions with the Women in the
      Military Self-Diagnosis (WMSD) Kit. The Kit contains commercially available
      diagnostic devices and the investigator-developed WMSD Decision-Making Guide. A
      randomized, two-factor, controlled trial design was used to compare accuracy
      rates among six experimental training conditions, ranging from simplest
      (videotape) to intensive (videotape + psychomotor skill training + cognitive
      rehearsal training). Standardized noninfectious specimens were used to measure
      diagnostic accuracy. The volunteer participants included Army, Navy, Air Force,
      and Marine women (N = 265) aged 18 to 58 years. There were no differences in
      accuracy rates among the six levels of training intensity, thus predeployment
      training for accurate use of the Kit requires only a 23-minute videotape. Overall
      diagnostic accuracy was 80.8% and self-treatment accuracy was 79.9%, which exceed
      our criterion of >=75%. Self-treatment commission error rate was 7.6% and
      omission error rate was 12.5%, which meet or exceed criteria of <=10% and <=15%.
      Briefly, predeployment training with the WMSD Kit shows great promise for
      improving military women's health during deployment. 

PMID- 25939112
TI  - Biliary leak rates after cholecystectomy and intraoperative cholangiogram in
      surgical residency.
AB  - Postoperative bile leak (BL) after cholecystectomy is a rare but dreaded
      complication, and is felt to be increased during surgical training. We sought to
      determine the incidence of BL after selective intraoperative cholangiogram (IOC)
      at a teaching hospital and identify risk factors for predicting BLs. A
      retrospective review was performed analyzing all cholecystectomy with IOCs
      between September 2004 and September 2011. Residents performed under staff
      supervision. Of 1,799 cholecystectomies performed during the study period, only
      96 (5.3%) were with IOCs (mean age 43, 65% female) and 4 BLs occurred (4.2%, 1
      major duct injury, 3 cystic duct stump leaks). Univariate analysis demonstrated
      that male gender, significant medical comorbidities, case duration, preoperative
      endoscopic retrograde cholangiopancreatography, and surgery type (laparoscopic
      versus open) increased the patient's risk of BL; however, age, performance of
      secondary procedures, common bile duct exploration, resident level (PGY), and
      diagnosis did not increase BL risk. Multivariate regression revealed that only
      surgery type lead to an increased risk of BL (p = 0.001) (OR 31.61, 95% CI 3.96
      252.18). Patient factors and PGY level did not significantly affect BL rates,
      although open and converted procedures were associated with higher rates,
      suggesting an increased risk of a BL with more complex cases. 

PMID- 25939114
TI  - Medical evacuation of French forces for dental emergencies: Operation Serval.
AB  - OBJECTIVES: The objectives of this study were to (1) quantify the number of
      intratheater dental Medical evacuations (MEDEVACs) required for French Soldiers
      in Mali during Operation Serval and (2) determine a Soldier's time away from
      their unit because of MEDEVAC, dental treatment, and return to unit. METHODS:
      Data concerning MEDEVACs occurring during Operation Serval were recorded by the
      Patient Evacuation Coordination Center. MEDEVACs resulting from
      oral/facial/dental conditions were evaluated for the period from February 15,
      2013 to May 15, 2013. RESULTS: Fifty-four (15.7%) of the 338 MEDEVACs recorded
      were required to treat dental emergencies. Dental emergencies accounted for 54
      (23.9%) of nonbattle injury MEDEVACs. Soldiers evacuated for dental problems were
      unavailable to their units an average of 10.5 days. CONCLUSIONS: French military
      personnel often require MEDEVAC to treat dental problems occurring in the theater
      of operation. Dental casualties requiring MEDEVAC are absent from their units for
      almost 2 weeks, which could drastically decrease their operational capacity and
      ability to complete their mission. Predeployment dental readiness and the
      presence of a dental surgeon in close proximity to deployed forces may reduce the
      number of MEDEVACs required and reduce the time away from the unit.

PMID- 25939113
TI  - Risk of dental disease non-battle injuries and severity of dental disease in
      deployed U.S. Army personnel.
AB  - Dental Disease and Non-Battle Injuries (D-DNBI) continue to be a problem among
      U.S. Army active duty (AD), U.S. Army National Guard (ARNG), and U.S. Army
      Reserve (USAR) deployed soldiers to Operation Iraqi Freedom/Operation New Dawn in
      Iraq and Operation Enduring Freedom in Afghanistan. A previous study reported the
      annual rates to be 136 D-DNBI per 1,000 personnel for AD, 152 for ARNG, and 184
      for USAR. The objectives of this study were to describe D-DNBI incidence and to
      determine risk factors for dental encounters and high severity diagnoses for
      deployed soldiers. The 78 diagnoses were classified into three categories based
      on severity. Poisson regression was used to compare D-DNBI rates and logistic
      regression was used to analyze the risk of high severity D-DNBI. In both
      campaigns, Reserve had a higher risk of D-DNBI than active duty. For Afghanistan,
      ARNG and USAR demonstrated over 50% increased risk of D-DNBI compared to AD. In
      Iraq, USAR had a 17% increased risk over AD. Females had a higher risk of D-DNBI
      (>50%) compared to males in both campaigns. High severity D-DNBI made up 2.77% of
      all diagnoses. Within Afghanistan, there was a 4.6% increased risk of high
      severity D-DNBI for each additional deployment month. 

PMID- 25939115
TI  - Auricular acupuncture for sleep disturbance in veterans with post-traumatic
      stress disorder: a feasibility study.
AB  - The purpose of this study was to examine the feasibility and acceptability of an
      auricular acupuncture (AA) insomnia regimen among Operation Iraqi Freedom and
      Operation Enduring Freedom veterans with post-traumatic stress disorder and sleep
      disturbance. Secondarily, this study examined the effect of an AA insomnia
      regimen on objective sleep times by wrist actigraphy, subjective sleep times by
      sleep diary, and sleep quality ratings utilizing the Pittsburg Sleep Quality
      Index. Veterans (n = 30) were randomized to receive a 3-week AA insomnia regimen.
      Veterans receiving the AA insomnia regimen reported it as a more acceptable
      treatment for sleep disturbance than subjects in the control group (AA group
      median = 5 vs. control group median = 3, p = 0.004). Significant differences
      between groups were found on the sleep quality and daytime dysfunction components
      of the Pittsburgh Sleep Quality Index (p = 0.003, p = 0.004). No other
      significant differences between groups were found for objective and subjective
      sleep measures. These results suggest that an AA insomnia regimen may improve
      sleep quality and daytime dysfunction among veterans with post-traumatic stress
      disorder. Future, large-scale, prospective clinical trials are needed to examine
      AA effects on sleep. 

PMID- 25939116
TI  - Airworthiness testing of medical maggots.
AB  - An investigation was conducted to test and certify medicinal maggots to
      facilitate rapid healing of traumatic and chronic wound infections in Wounded
      warriors being transported onboard military aircraft. Our specific aims included
      (1) to test the ability of medical grade larvae to withstand the rigors of U.S.
      Army aeromedical certification, including tolerance to change in pressure,
      temperature, and humidity inside ground-based chambers; (2) to evaluate the
      efficacy of the medical grade larvae during a high-vibration rotary-wing medical
      transport flight; and (3) to gain U.S. Army aeromedical certification and U.S.
      Air Force safe-to-fly approval and begin the steps needed to deploy/implement the
      use of medicinal maggots in patient care regimes for medical airlift standard
      operating procedures. This report outlines the ground-based and initial air-based
      tests performed during the study. Maggot mortality was very low during all tests,
      with a mortality rate of less than 1%. Maggot growth rates in wound arenas were
      mixed but generally depended on temperature. Overall, the results of these tests
      suggest that medicinal maggots can withstand the rigors of aeromedical evacuation
      flights in simulated flight environments and rotary- or fixed-wing aircraft. 

PMID- 25939117
TI  - Portable traumatic brain injury detection with near-infrared technology:
      infrascanner model 2000.

PMID- 25939118
TI  - Neurocognitive Performance is Not Degraded After Stellate Ganglion Block
      Treatment for Post-Traumatic Stress Disorder: A Case Series.
AB  - OBJECTIVE: To measure key neurocognitive performance effects following stellate
      ganglion block (SGB) administered to treat post-traumatic stress disorder (PTSD)
      symptoms. METHODS: Eleven patients diagnosed, screened, and scheduled for SGB to
      treat their PTSD symptoms were administered a panel of eight cognitive measures
      before and 1 to 3 weeks after undergoing this procedure. PTSD symptoms were
      evaluated using the Posttraumatic Stress Disorder Checklist-Military. RESULTS:
      One to three weeks post-SGB, none of the patients showed any statistically
      significant decline in neurocognitive performance. Rather, there was a clear
      trend in improvement, with four out of eight measures reaching statistical
      significance following SGB. All patients improved in PTSD symptoms with a mean
      improvement on Posttraumatic Stress Disorder Checklist-Military of 29.
      CONCLUSION: In this case series of 11 patients, SGB effectively treated PTSD
      symptoms and did not impair reaction time, memory, or concentration. Therefore,
      SGB should be considered as a viable treatment option for personnel with PTSD
      symptoms who will be placed in demanding conditions such as combat.

PMID- 25939119
TI  - Medical evacuation for unrecognized abdominal wall pain: a case series.
AB  - BACKGROUND: Chronic abdominal pain is a frequently encountered complaint in the
      primary care setting. The abdominal wall is the etiology of this pain in 10 to
      30% of all cases of chronic abdominal pain. Abdominal cutaneous nerve entrapment
      at the lateral border of the rectus abdominis muscle has been attributed as a
      cause of this pain. In the military health care system, patients with unexplained
      abdominal pain are often transferred to military treatment facilities via the
      Military Medical Evacuation (MEDEVAC) system. CASE SERIES: We present two cases
      of patients who transferred via MEDEVAC to our facility for evaluation and
      treatment of chronic abdominal pain. Both patients had previously undergone
      extensive laboratory evaluation, imaging, and invasive procedures, such as
      esophagogastroduodenoscopy before transfer. Upon arrival, history and physical
      examinations suggested an abdominal wall source to their pain, and both patients
      experienced alleviation of their abdominal wall pain with lidocaine and
      corticosteroid injection. CONCLUSION: This case series highlights the need for
      military physicians to be aware of abdominal wall pain. Early diagnosis of
      abdominal cutaneous nerve entrapment syndrome by eliciting Carnett's sign will
      limit symptom chronicity, avoid unnecessary testing, and even prevent medical
      evacuation.

PMID- 25939120
TI  - Case report: corpus cavernosum thrombosis occurring during a long-range aviation
      mission initially diagnosed as lymphoma.
AB  - A 23-year-old active duty United States Air Force air crew male presented to the
      flight medicine clinic in Germany after experiencing sudden onset penile pain
      while flying as part of a long-range operational mission. He was admitted to the
      German hospital and empirically treated for infection with antibiotics, which did
      not improve his symptoms. Initial magnetic resonance imaging of the pelvis with
      and without intravenous contrast was reported to be concerning for lymphoma,
      which prompted transport to a regional medical center in the United States.
      Further evaluation and review of the pelvic magnetic resonance imaging
      established a diagnosis of corpus cavernosum thrombosis. Conservative management
      with 3 months of standard anticoagulation therapy was effective in resolving the
      patient's symptoms. Corpus cavernosum thrombosis is a rare condition which
      appears to be associated with prolonged air travel that can easily be
      misdiagnosed as a much more serious condition; however, once accurate diagnosis
      is made, it is easily managed and treated. 

PMID- 25939121
TI  - Syphilitic hepatitis uncommon presentation of an old scourge.
AB  - BACKGROUND: Giant cell hepatitis is a rare entity in adults, accounting for 0.1%
      to 0.25% of liver disease in adults. Postinfantile giant cell hepatitis is often
      characterized by multinucleated giant cells on liver biopsy and a fulminant
      hepatitis. CASE REPORT: An active duty 36-year-old African-American male deployed
      to Kabul, Afghanistan, presented with jaundice 2 weeks after starting a
      testosterone analogue. He discontinued the supplement, but his jaundice persisted
      with up-trending bilirubin. Serologic testing was negative for hepatitis A, B, C,
      and E; cytomegalovirus; Epstein-Barr virus; herpes simplex virus; and human
      immunodeficiency virus. Evaluation for autoimmune hepatitis was negative.
      Magnetic resonance cholangiopancreatography was negative for obstruction. Liver
      biopsy revealed giant cell transformation of numerous hepatocytes and cholestatic
      hepatitis. Rapid plasma reagin was positive without physical findings. Treponema
      pallidum hemagglutination assays confirmed the diagnosis of latent syphilis. He
      was started on penicillin treatment with rapid improvement of bilirubin,
      creatinine, and hepatic synthetic function, all of which eventually normalized.
      CONCLUSION: Postinfantile giant cell hepatitis is a severe form of hepatitis that
      has several different potential etiologies, 2 of which were present in this
      patient: androgenic supplements and infection. This case highlights syphilis as
      an unusual but treatable cause of giant cell hepatitis. Testing for syphilis
      should be considered in any persistent liver injury.

PMID- 25939122
TI  - Spindle cell variant of ameloblastic carcinoma: a case report and review of
      literature.
AB  - Ameloblastic carcinoma is a rare and malignant odontogenic tumor. Approximately,
      100 cases of ameloblastic carcinomas have been reported in the literature, with
      fewer than 10 reported cases of an even more rare variant with spindle-cell
      differentiation. Although it is presumed that most ameloblastic carcinomas arise
      de novo, it also appears capable of proliferating as carcinoma ex ameloblastoma.
      Without a full past history, the exact origin of these tumors can be unclear. The
      exact classification becomes further questionable when both an intraosseous and
      peripheral tumor exists. This currently reported case has been present for at
      least 4 years before the patient presenting for care. However, without prior
      biopsy, the etiology and category of this ameloblastic carcinoma is speculative.
      Our case represents a histologically unequivocal case of ameloblastic carcinoma.
      Based on tumor morphology, questions still remain, as to whether it arose de
      novo, or as carcinoma ex ameloblastoma. The possibility of categorizing the
      current lesion as a spindle cell variant also exists because of the presence of a
      prominent population of malignant epithelial spindled cells arranged in
      fascicles. The authors believe that this ameloblastic carcinoma would best be
      subclassified as a rare spindle cell variant, based on the prominent spindle cell
      component. 

PMID- 25939123
TI  - Aggressive gastrointestinal stromal tumor with spinal metastases: a case report.
AB  - We report a case of a 56-year-old male who presented with several month history
      of severe low back pain. Physical examination revealed generalized tenderness at
      his thoracolumbar spine without notable neuromuscular findings. Radiographs
      revealed a chronic compression fracture of T10 and T11 with anterior height loss.
      Subsequent magnetic resonance imaging demonstrated multiple lytic lesions in the
      thoracolumbar spine without canal compromise. During his hospital stay, he
      developed acute cord compression with loss of motor and sensory levels below T12
      and an absence of sphincter tone. The patient was taken for emergent multilevel,
      posterior decompression and fusion with biopsy of the lesion. Microscopic
      examination of the tissue in addition to immunohistochemical analysis utilizing
      CD117-antibody/c-kit revealed gastrointestinal stromal tumor. Further workup
      revealed the primary tumor to be intra-abdominal and the patient was subsequently
      begun on adjuvant chemotherapy. Gastrointestinal stromal tumors should be
      considered in the workup of patients with bone metastasis with an unknown primary
      malignancy. 

PMID- 25939124
TI  - Chronic iritis associated with cutaneous leukocytoclastic vasculitis.
AB  - Cutaneous leukocytoclastic vasculitis (LCV) is a systemic condition that can be
      associated with iritis. LCV is characterized as a small-vessel vasculitis of the
      cutaneous area. The disease demonstrates purple lesions on the skin due to the
      destruction of small cutaneous blood vessels. These lesions are palpable and most
      often coalesce forming larger patches on the surface of the skin. During early
      stages of LCV, the disease can be undetected due to the infrequency and small
      size of the skin lesions. As such, the patient might go undiagnosed for years
      while having symptoms of LCV or iritis of unknown etiology. This article
      discusses the correlation seen with LCV and iritis. We report a case on a patient
      that presented to our clinic with a history of bilateral chronic iritis. After
      extensive laboratory testing, we concluded that the chronicity of her iritis was
      due to her LCV. The correlation between LCV and iritis was not evident for
      several years in our patient. We also discuss the correlation with systemic
      Sjogren's syndrome and LVC and how these two separate diseases are linked in many
      patients. We will illustrate the importance of serological testing, imaging, and
      skin lesion biopsy for the diagnosis of LCV. 

PMID- 25939125
TI  - Author's reply to uses of clopidogrel, rosuvastatin and digoxin on the risk of
      acute pancreatitis.

PMID- 25939126
TI  - Esmolol for tight heart rate control in patients with STEMI: Design and rationale
      of the beta-blocker in acute myocardial infarction (BEAT-AMI) trial.

PMID- 25939127
TI  - Amitriptyline pharmacologically preconditions rat hearts against cardiac ischemic
      reperfusion injury.
AB  - BACKGROUND/OBJECTIVES: Amitriptyline (AMY) is a tricyclic anti-depressant that
      has recently been shown to have anti-inflammatory properties. We investigated
      whether AMY is cardioprotective against reperfusion injury in ex-vivo rat hearts.
      METHODS: Thirty adult Sprague-Dawley rat hearts were perfused ex-vivo in a
      Langendorff apparatus. All hearts except SHAM (n = 6, perfused for 110 min.)
      received 30 min no-flow ischemia followed by 40 min reperfusion (I-R). One group
      (n = 6) was untreated before I-R (non-preconditioned; NPC), another non
      preconditioned group was perfused with 10 MUM amitriptyline for 30 min before I-R
      (NPC-AMY, n = 6). One group was preconditioned with 3 * 5-minute periods of
      ischemia before I-R (PC, n = 6) and a fifth group was preconditioned in the
      presence of 10 MUM amitriptyline (PC-AMY, n = 6). p38 phosphorylation and HMGB1
      levels were quantified using Western blots. Data was analysed using multiway
      ANOVAs with Tukey HSD and linear regression models with Sobel mediator tests.
      RESULTS: NPC hearts recovered poorly (LVDP recovered to 26.5 +/- 10.5% of pre
      ischemic values, compared to PC hearts (82.8 +/- 14.9%: P < 0.05)). PC-AMY (69.9
      +/- 6.16%) and NPC-AMY (90.3 +/- 10.0%) groups both recovered well (P < 0.05).
      The Sobel mediator test suggested that p38 activity may be indirectly involved in
      the amitriptyline induced cardioprotection (P < 0.05). HMGB1 was lower in
      amitriptyline treated hearts compared to the non-preconditioned hearts (P < 0.05)
      but the multiway ANOVA test suggests that HMGB1 was not involved in amitriptyline
      induced protection. CONCLUSIONS: Amitriptyline at 10 MUM protects hearts against
      ischemic-reperfusion injury which may be partially mediated through p38
      phosphorylation.

PMID- 25939128
TI  - Metabolic syndrome, major depression, generalized anxiety disorder, and ten-year
      all-cause and cardiovascular mortality in middle aged and elderly patients.
AB  - BACKGROUND: Studies investigating specifically whether metabolic syndrome (MetS)
      and common psychiatric disorders are independently associated with mortality are
      lacking. In a middle-aged general population, we investigated the association of
      the MetS, current major depressive episode (MDE), lifetime MDE, and generalized
      anxiety disorder (GAD) with ten-year all-cause and cardiovascular disease
      mortality. METHODS: From February 2003 until January 2004, 1115 individuals aged
      45 years and older were randomly selected from a primary care practice and
      prospectively evaluated for: (1) MetS (The World Health Organization [WHO],
      National Cholesterol Education Program/Adult Treatment Panel III and
      International Diabetes Federation [IDF] definitions); (2) current MDE and GAD,
      and lifetime MDE (Mini International Neuropsychiatric Interview); and (3)
      conventional cardiovascular risk factors. Follow-up continued through January,
      2013. RESULTS: During the 9.32 +/- 0.47 years of follow-up, there were 248
      deaths, of which 148 deaths were attributed to cardiovascular causes. In women,
      WHO-MetS and IDF-MetS were associated with greater all-cause (HR-values range
      from 1.77 to 1.91; p-values <= 0.012) and cardiovascular (HR-values range from
      1.83 to 2.77; p-values <= 0.013) mortality independent of cardiovascular risk
      factors and MDE/GAD. Current GAD predicted greater cardiovascular mortality (HR
      values range from 1.86 to 1.99; p-values <= 0.025) independently from MetS and
      cardiovascular risk factors. In men, the MetS and MDE/GAD were not associated
      with mortality. CONCLUSIONS: In middle aged women, the MetS and GAD predicted
      greater 10-year cardiovascular mortality independently from each other; 10-year
      all-cause mortality was independently predicted by the MetS. MetS and GAD should
      be considered important and independent mortality risk factors in women.

PMID- 25939129
TI  - Acute coronary syndrome or takotsubo syndrome: Most probably both of them, the
      first has triggered the second.

PMID- 25939130
TI  - Reply to the letter to the editor on Peters S. Unusual case of myocardial
      bridging of the circumflex artery and initially intractable chest pain.

PMID- 25939131
TI  - Validation of the Weight Concerns Scale Applied to Brazilian University Students.
AB  - The aim of this study was to evaluate the validity and reliability of the
      Portuguese version of the Weight Concerns Scale (WCS) when applied to Brazilian
      university students. The scale was completed by 1084 university students from
      Brazilian public education institutions. A confirmatory factor analysis was
      conducted. The stability of the model in independent samples was assessed through
      multigroup analysis, and the invariance was estimated. Convergent, concurrent,
      divergent, and criterion validities as well as internal consistency were
      estimated. Results indicated that the one-factor model presented an adequate fit
      to the sample and values of convergent validity. The concurrent validity with the
      Body Shape Questionnaire and divergent validity with the Maslach Burnout
      Inventory for Students were adequate. Internal consistency was adequate, and the
      factorial structure was invariant in independent subsamples. The results present
      a simple and short instrument capable of precisely and accurately assessing
      concerns with weight among Brazilian university students. 

PMID- 25939132
TI  - The Muscle Appearance Satisfaction Scale: A factorial analysis of validity and
      reliability for its use on adult Chinese male weightlifters.
AB  - Muscle dysmorphia (MD) is the distorted perception of men's own muscle
      appearance. The increasing popularity of weightlifting in Chinese men suggests
      the presence of MD. The study assessed the validity and reliability of the Muscle
      Appearance Satisfaction Scale (MASS) for its use on adult Chinese males.
      Exploratory and confirmatory factor analyses of responses from 225 and 592
      participants confirmed the same five factors for the 17-item Chinese version as
      the original MASS (CFI=.931, RMSEA=.052). The internal consistency for all
      factors were acceptable (Cronbach's alpha=.636 to .737). Correlation levels of
      its subscales with converging measurements indicated that the revised MASS is
      effective in assessing MD in Chinese male weightlifters. Differences in the
      importance of the factors suggest an influence of Chinese culture in the symptoms
      of MD and the need of assessing the MASS with populations from distinct
      demographics in China and from different cultures. 

PMID- 25939133
TI  - Young driver crash rates by licensing age, driving experience, and license phase.
AB  - BACKGROUND: Few studies have concurrently assessed the influence of age and
      experience on young driver crashes, in particular in the post-Graduated Driver
      Licensing (GDL) era. Further, little attention is given to the transition from
      intermediate to full licensure. We examined the independent and joint
      contributions of licensing age, driving experience, and GDL license phase on
      crash rates among the population of young New Jersey (NJ) drivers. METHODS: From
      a unique linked database containing licensing and crash data, we selected all
      drivers who obtained their NJ intermediate license at 17-20 years old from 2006
      2009 (n=410,230). We determined the exact age at which each driver obtained an
      intermediate and full license and created distinct, fixed cohorts of drivers
      based on their age at intermediate licensure. For each cohort, we calculated and
      graphed observed monthly crash rates over the first 24 months of licensure.
      Further, we examined crash rates by age at licensure, driving experience (i.e.,
      time since licensure), and license phase. RESULTS: First-month crash rates were
      higher among the youngest drivers (licensed at 17y0m). Drivers who were licensed
      later experienced a reduced "steepness" in the slope of their crash rates in the
      critical initial months of driving, but there did not appear to be any
      incremental benefit of later licensure once drivers had six months of driving
      experience. Further, at each age, those with more driving experience had lower
      crash rates; however, the benefit of increased experience was greatest for the
      substantial proportion of teens licensed immediately after becoming eligible (at
      17y0m). Finally, independent of age and experience, teen drivers' crash risk
      increased substantially at the point of transition to a full license, while
      drivers of a similar age who remained in the intermediate phase continued to
      experience a decline in crash rates. CONCLUSION: Age and driving experience
      interact to influence crash rates. Further, independent of these two factors,
      there is an abrupt increase in crash risk at the point of transition from
      intermediate to full licensure. Future studies should investigate whether this
      increase is accounted for by a change in driving exposure, driving behaviors,
      and/or other factors.

PMID- 25939134
TI  - A systematic review of the literature on safety measures to prevent railway
      suicides and trespassing accidents.
AB  - This review covers a central aspect in railway safety which is the prevention of
      suicides and trespassing accidents. The paper attempts to answer the following
      research question: 'What measures are available to reduce railway suicide and
      trespass, and what is the evidence for their effectiveness?' The review is based
      on 139 relevant publications, ranging from 1978 to 2014. The analysis aimed to
      identify the past and current trend in the prevention practice by looking both
      quantitatively and qualitatively at the recommended measures. According to the
      results, there has been a constant focus on suicide prevention, and only
      relatively recent interest in trespass countermeasures. The content analysis
      revealed 19 main preventative categories which include more than 100 specific
      measures. We identified 16 common categories against railway suicide and
      trespass, and 3 categories of specific measures to prevent suicide. There are
      only 22 studies which provide empirical support for the effectiveness of
      measures. Actual combinations of measures are barely evaluated, but several
      challenges emerge from the literature. The discussion focuses on the need for a
      unified approach to suicide and trespass prevention, and on the importance to
      consider the effect mechanism of the measures in order to design better
      interventions. 

PMID- 25939136
TI  - Congruency effects on the basis of instructed response-effect contingencies.
AB  - Previous research indicated that stimulus-response congruency effects can be
      obtained in one task (the diagnostic task) on the basis of the instructed
      stimulus-response mappings of another task (the inducer task) and this without
      having executed the instructions of the inducer task once. A common
      interpretation of such finding is that instructed stimulus-response mappings are
      implemented into functional associations, which automatically trigger responses
      when being irrelevant and this without any practice. The present study
      investigated whether instruction-based congruency effects are also observed for a
      different type of instructions than instructed S-R mappings, namely instructed
      response-effect contingencies. In three experiments, instruction-based congruency
      effects were observed in the diagnostic task when the instructions of the inducer
      task specified response-effect contingencies. On the one hand, our results
      indicate that instruction-based congruency effects are not restricted to
      instructed S-R mappings. On the other hand, our results suggest that the
      representations that mediate these effects do not specify the nature of the
      relation between response and effect even though this relation was explicitly
      specified by the instructions. 

PMID- 25939135
TI  - Incidence and costs of bicycle-related traumatic brain injuries in the
      Netherlands.
AB  - The main cause of death and serious disability in bicycle accidents is traumatic
      brain injury (TBI). The aim of this population-based study was to assess the
      incidence and costs of bicycle-related TBI across various age groups, and in
      comparison to all bicycle-related injuries, to identify main risk groups for the
      development of preventive strategies. Data from the National Injury Surveillance
      System and National Medical Registration were used for all patients with bicycle
      related injuries and TBI who visited a Dutch emergency department (ED) between
      1998 and 2012. Demographics and national, weighted estimates of injury mechanism,
      injury severity and costs were analysed per age group. Direct healthcare costs
      and indirect costs were determined using the incidence-based Dutch Burden of
      Injury Model. Between 1998 and 2012, the incidence of ED treatments due to
      bicycle-related TBI strongly increased with 54%, to 43 per 100,000 persons in
      2012. However, the incidence of all bicycle-related injuries remained stable,
      from 444 in 1998 to 456/100,000 in 2012. Incidence of hospital admission
      increased in both TBI (92%) and all injuries from cycling (71%). Highest increase
      in incidence of both ED treatments and hospital admissions was seen in adults
      aged 55+. The injury rate of TBI per kilometre travelled increased (44%) except
      in children, but decreased (-4%) for all injuries, showing a strong decrease in
      children (-36%) but an increase in men aged 25+, and women aged 15+. Total costs
      of bicycle-related TBI were ?74.5 million annually. Although bicycle-related TBI
      accounted for 9% of the incidence of all ED treatments due to cycling, it
      accounted for 18% of the total costs due to all bicycle-related injuries (?410.7
      million). Children and adolescents (aged 0-24) had highest incidence of ED
      treatments due to bicycle-related injuries. Men in the working population (aged
      15-64) had highest indirect costs following injuries from cycling, including TBI.
      Older cyclists (aged 55+) were identified as main risk group for TBI, as they had
      highest ED attendance, injury rate, injury severity, admission to hospital or
      intensive care unit, and costs. Incidence of ED treatments due to cycling are
      high and often involve TBI, imposing a high burden on individuals and society.
      Older cyclists aged 55+ were identified as main risk group for TBI to be targeted
      in preventive strategies, due to their high risk for (serious) injuries and ever
      increasing share of ED visits and hospital admissions. 

PMID- 25939137
TI  - Imagination inflation in the mirror: Can imagining others' actions induce false
      memories of self-performance?
AB  - Imagining oneself performing a simple action can trigger false memories of self
      performance, a phenomenon called imagination inflation. However, people can, and
      often do, imagine others' behavior and actions. According to a visual-similarity
      account, imagining another person's actions should induce the same kind of memory
      error, a false memory of self-performance. We tested this account in three
      experiments, in which performance was followed by imagination. In the imagination
      phase, participants were asked to either imagine themselves or to imagine another
      person performing actions, some of which were not previously performed. Two weeks
      later, a surprise source-memory test was administered in which participants had
      to decide whether a depicted action had been performed or not performed. Results
      revealed that imagining another person can trigger false memories of self
      performance. However, visual similarity between performance and imagination
      predicted the amount of false memories only for other-imagination but not for
      self-imagination. These findings are consistent with research suggesting that
      other- and self-imagination rely on different mechanisms: While other-imagination
      primarily involves visual imagery, self-imagination primarily involves motor
      imagery. Accordingly, false action memories from other-imagination may result
      from visual similarity, whereas false action memories from self-imagination may
      result from motor simulation. 

PMID- 25939138
TI  - Social presence and the composite face effect.
AB  - A robust finding in social psychology research is that performance is modulated
      by the social nature of a given context, promoting social inhibition or
      facilitation effects. In the present experiment, we examined if and how social
      presence impacts holistic face perception processes by asking participants, in
      the presence of others and alone, to perform the composite face task. Results
      suggest that completing the task in the presence of others (i.e., mere co-action)
      is associated with better performance in face recognition (less bias and higher
      discrimination between presented and non-presented targets) and with a reduction
      in the composite face effect. These results make clear that social presence
      impact on the composite face effect does not occur because presence increases
      reliance on holistic processing as a "dominant" well-learned response, but
      instead, because it increases monitoring of the interference produced by
      automatic response. 

PMID- 25939139
TI  - Costs of storing colour and complex shape in visual working memory: Insights from
      pupil size and slow waves.
AB  - We investigated the impact of perceptual processing demands on visual working
      memory of coloured complex random polygons during change detection. Processing
      load was assessed by pupil size (Exp. 1) and additionally slow wave potentials
      (Exp. 2). Task difficulty was manipulated by presenting different set sizes (1,
      2, 4 items) and by making different features (colour, shape, or both) task
      relevant. Memory performance in the colour condition was better than in the shape
      and both condition which did not differ. Pupil dilation and the posterior N1
      increased with set size independent of type of feature. In contrast, slow waves
      and a posterior P2 component showed set size effects but only if shape was task
      relevant. In the colour condition slow waves did not vary with set size. We
      suggest that pupil size and N1 indicates different states of attentional effort
      corresponding to the number of presented items. In contrast, slow waves reflect
      processes related to encoding and maintenance strategies. The observation that
      their potentials vary with the type of feature (simple colour versus complex
      shape) indicates that perceptual complexity already influences encoding and
      storage and not only comparison of targets with memory entries at the moment of
      testing. 

PMID- 25939141
TI  - A closer look at Iranian migration to the United States.

PMID- 25939140
TI  - Impact of DEFB1 gene regulatory polymorphisms on hBD-1 salivary concentration.
AB  - OBJECTIVES: Human beta-defensin 1 (hBD-1) is an antimicrobial peptide involved in
      epithelial defence of various tissues, also present in the saliva. Individual
      genetic variations within the DEFB1 gene, encoding for hBD-1, could influence
      gene expression and protein production. DESIGN: Three DEFB1 polymorphisms at 5'
      untranslated region (UTR), -52G > A (rs1799946), -44C > G (rs1800972) and -20G >
      A (rs11362), and two polymorphisms at DEFB1 3' UTR, c*5G > A (rs1047031) and
      c*87A > G (rs1800971), were analysed by direct sequencing and correlated with hDB
      1 salivary concentration (tested with enzyme-linked immunosorbent assay (ELISA))
      in 40 healthy subjects. RESULTS: Significant associations were found between
      individuals presenting different DEFB1 polymorphisms at positions -52 and -44 of
      the gene and hBD-1 salivary concentrations: -52 G/G carriers had higher levels of
      protein than G/A and A/A; -44C/G subjects showed a higher protein concentration
      than homozygous wild-type C/C. For the -20G > A, c*5G > A and c*87A > G
      polymorphisms, no statistically significant differences were found. Combined
      haplotype analysis confirmed the results obtained considering the single
      nucleotide polymorphisms (SNPs) singularly. CONCLUSION: Polymorphisms in the
      DEFB1 gene influence hBD-1 production and, therefore, could modify the innate
      immune system responses and, consequently, the oral health.

PMID- 25939142
TI  - CKD in disadvantaged populations.

PMID- 25939143
TI  - Measles and membership.

PMID- 25939145
TI  - A student's perspective.

PMID- 25939147
TI  - Encouraging development.

PMID- 25939148
TI  - Are we our brothers' keepers?

PMID- 25939149
TI  - [Critical care nephrology: concepts and perspectives].

PMID- 25939150
TI  - [Pathophysiology and clinical challenges of septic acute kidney injury].

PMID- 25939151
TI  - [Therapeutic strategies in sepsis and septic shock].

PMID- 25939152
TI  - [Therapeutic consideration in the intensive care unit of patients with chronic
      kidney disease or end-stage renal disease].

PMID- 25939153
TI  - [Cardiorenal syndrome in ICU/CCU].

PMID- 25939154
TI  - [Renal replacement therapy for AKI].

PMID- 25939155
TI  - [Management of severe respiratory failure and acute respiratory distress
      syndrome].

PMID- 25939156
TI  - [Role of nephrology consultation in intensive care unit].

PMID- 25939157
TI  - [Pediatric AKI in critical care nephrology].

PMID- 25939158
TI  - High efficiency liposome-mediated transfection of the tyrosinase gene to cultured
      cells: a model for the gene therapy of hair color restoration.

PMID- 25939159
TI  - Re-evaluation of FGF-1 as a potent mitogen for hepatocytes.

PMID- 25939160
TI  - Detection by electron microscopy of endogenous viruses in Aedes krombeini (H.)
      cell line.

PMID- 25939161
TI  - Human omental mesothelial cells: a simple method for isolation and discrimination
      from endothelial cells.

PMID- 25939162
TI  - A fish cell line CHSE-sp exposed to long-term cold temperature retains viability
      and ability to support viral replication.

PMID- 25939163
TI  - HPAC, a new human glucocorticoid-sensitive pancreatic ductal adenocarcinoma cell
      line.
AB  - A new human pancreatic cancer (HPAC) cell line was established from a nude mouse
      xenograft (CAP) of a primary human pancreatic ductal adenocarcinoma. In culture,
      HPAC cells form monolayers of morphologically heterogenous, polar epithelial
      cells, which synthesize carcinoembryonic antigen, CA 19-9, CA-125, cytokeratins,
      antigens for DU-PAN-2, HMFG1, and AUA1, but do not express chromogranin A or
      vimentin indicative of their pancreatic ductal epithelial cell character. In the
      presence of serum, HPAC cell DNA synthesis was stimulated by insulin, insulin
      growth factor-I, epidermal growth factor, and TGF-alpha but inhibited by
      physiologic concentrations of hydrocortisone and dexamethasone. Dose-dependent
      inhibition of DNA synthesis was limited to steroids with glucocorticoid activity.
      The inhibitory effect of dexamethasone was abolished by the glucocorticoid
      antagonist RU 384862 Binding of [3H] dexamethasone to cytosolic proteins was
      specific and saturable at 4 degrees C. Scatchard analysis of binding data
      demonstrated a single class of high-affinity binding sites (K(d) = 3.8 +/- 0.9
      nM; B(max) = 523 +/- 128 fmol/mg protein). Western blot analysis revealed a major
      protein band that migrated at a M(r) of 96 kDa. Northern blot analysis identified
      an mRNA of approximately 7 kilobases which hybridized with a specific
      glucocorticoid receptor complementary-DNA probe (OB7). These findings support a
      role for glucocorticoids in the regulation of human malignant pancreatic cell
      function.

PMID- 25939164
TI  - Isolation and culture of somatotrophs from the pituitary of the rainbow trout:
      immunological and physiological characterization.
AB  - The aim of the present paper was to obtain somatotroph- and gonadotroph-enriched
      populations from collagenase dispersed pituitaries of male rainbow trout.
      Inasmuch as the percentage of immunoreactive gonadotrophs and somatotrophs
      present in pituitaries was higher at spermiation than at the beginning of
      spermatogenesis, we tried such a cell separation with fish at this stage of
      spermatogenesis. Cells were fractionated using their differences in buoyant
      density with centrifugation in Percoll solutions. The use of Percoll linear
      gradients (1.110 to 1.027 g/ml) showed that somatotroph cells have a density of
      between 1.102 and 1.064 g/ml whereas gonadotrophs are spread over the range of
      the gradient. It was thus possible, by using linear or discontinuous Percoll
      gradients, to obtain 95 to 67% (mean 80%) enriched somatotropic cell fractions
      while no enriched gonadotropic cell fractions were collected. The fractionated
      cells kept their ability to be cultured and to be responsive to specific
      secretagogues. Somatostatine induced a 80 to 85% decrease in growth hormone
      release per somatotroph in the initial cell suspension as well as in the
      different cell fractions. On the other hand, the basal growth hormone release per
      cell was lower in the fractions containing cells with a density lower than 1.062
      g/ml. Inversely, the gonadotrophs have a basal release per cell independent of
      their density, and this is also available for their responsiveness to salmon
      gonadotropin-releasing hormone.

PMID- 25939165
TI  - Transdifferentiation of outgrowth cells and cultured epithelial cells from swine
      trachea.
AB  - The morphologic and functional properties of explant out-growth cells and
      epithelial cells isolated from swine trachea epithelium by proteolysis were
      examined. A mixed population of ciliated, serous, and basal cells, obtained from
      out-growths, from proteolysis of trachea epithelium, and from unattached explants
      in organ culture, all yielded cell cultures that werecomposed almost entirely of
      mucus-secreting cells. When the cells were grown in primary or secondary culture
      on a modified collagen matrix in supplemented HAM:DMEM (1:1) medium they
      expressed a mucus-secreting phenotype with numerous mucus granules at various
      stages of maturation and incorporated [3H]GlcN and 35SO4 into secreied mucin
      glycoproteins. Results obtained in these studies suggest that extensive
      transdifferentiation of ciliated and serous cells to mucus-secreting-cells occurs
      after the release and during subsequent attachment and culture. Ciliated cells
      containing mucus granules were seen in various stages of cilia resorption. Basal
      cells containing mucus granules were also frequently observed. The number of
      mucus-secreting cells and the synthesis of mucin glycoproteins increased
      dramatically with time of attachment and culture, whereas cell proliferation,
      population doubling time of 72 h, and incorporation of [3H]-thymidine into DNA
      increased much more slowly. The number of mucus-secreting cells correlated
      closely with the level of secretion of mucin glycoproteins. Taken collectively,
      these studies help to elucidate the transdifferentiation process, which
      dramatically increases the number of mucus-secreting cells after disruption and
      release of epithelial cells from swine tracheobronchial epithelium. A similar
      mechanism involving disruption of the extracellular matrix may be involved in the
      stimulation of hypersecretion of mucus and mucin glycoproteins by chemical and
      infections irritants.

PMID- 25939166
TI  - Stable, position-related responses to retinoic acid by chick limb-bud mesenchymal
      cells in serum-free cultures.
AB  - Retinoic acid (RA) has dramatic effects on limb-skeletal patterning in vivo and
      may well play a pivotal role in normal limb morphogenesis. RA's effects on the
      expression of pattern-related genes in the developing limb are probably mediated
      by cytoplasmic RA-binding proteins and nuclear RA-receptors. Little is known,
      however, about how RA modifies specific cellular behaviors required for skeletal
      morphogenesis. Earlier studies supported a role for regional differences in RA
      concentration in generating the region-specific cell behaviors that lead to
      pattern formation. The present study explores the possibility that position
      related, cell-autonomous differences in the way limb mesenchymal cells respond to
      RA might have a role in generating pattern-related cell behavior. Mesenchymal
      cells from different proximodistal regions of stage 21-22 and 23-24 chick wing
      buds were grown in chemically defined medium and exposed to 5 or 50 ng/ml of RA
      for 4 days in high-density microtiter cultures. The effects of RA on
      chondrogenesis in these cultures clearly differed depending on the limb region
      from which the cells were isolated. Regional differences in RA's effects on
      growth over 4 days in these cultures were less striking. The region-dependent
      responses of these cells to RA proved relatively stable in culture despite
      ongoing cytodifferentiation. This serum-free culture model will be useful in
      exploring the mechanisms underlying the region-dependent responsiveness of these
      cells to RA.

PMID- 25939167
TI  - The mRNA expression of the human 1,25-dihydroxyvitamin D3 receptor and the c-myc
      protooncogene in cultured human keratinocytes.
AB  - The human vitamin D receptor mRNA expression in preconfluent human cultured
      keratinocytes was upregulated by treatment of these cells with 10(-8) M
      1,25(OH)2D3 for 24 hours. Additionally, human c-myc mRNA expression was decreased
      in a dose dependent manner by 1,25(OH)2D3 in both preconfluent and confluent
      cultured human keratinocytes.

PMID- 25939168
TI  - Phenotypic modulation of cultured endothelial cells in collagen matrices induced
      by tumor necrosis factor alpha.
AB  - The effect of tumor necrosis factor alpha on vascular endothelial cells was
      analyzed using a collagen-embedded, three-dimensional culture system, focusing on
      angiogenesis and expression of cell adhesion molecules. When the endothelial
      cells were cultured between two layers of type-I collagen gel, they reorganized
      into a network of branching and anastomosing tubular structures. Once the
      structure was formed, the cells did not undergo further division. Addition of
      tumor necrosis factor alpha at 10 to 500 U/ml to the overlaid culture medium
      inhibited this tube-forming process and enhanced their survival, whereas it
      suppressed cell growth in monolayer. To test its effect on the expression of cell
      adhesion molecules, the collagen was digested, and the dispersed cells were
      stained with anti-intercellular adhesion molecule-1 and endothelial-leukocyte
      adhesion molecule-1 monoclonal antibodies. Tumor necrosis factor alpha
      upregulated the expressions of both molecules for an extended period of time.
      Even in the absence of tumor necrosis factor alpha, the cells embedded in
      collagen matrices expressed small amounts of these adhesion molecules. These
      results indicate that endothelial cells display phenotypic changes in collagen
      matrices and modulatory response to tumor necrosis factor alpha.

PMID- 25939169
TI  - Paucity of PCPs may hurt children the most.

PMID- 25939171
TI  - A conversation with David A. Fleming, MD. Medical practices struggle with change.

PMID- 25939170
TI  - Managed Medicaid braces for influx of ex-inmates.

PMID- 25939172
TI  - Homeopathic medicine should have a role in managed care.

PMID- 25939173
TI  - PCSK9 inhibitors on the way.

PMID- 25939174
TI  - New medical devices winning faster approvals from FDA.

PMID- 25939175
TI  - New test gauges danger of rejection when children need organ transplants.

PMID- 25939177
TI  - Decline in cervical cancer death rate ends.

PMID- 25939176
TI  - Hepatitis C meets its match.

PMID- 25939178
TI  - High-cost drugs. Where's the ROI?

PMID- 25939179
TI  - Health plans, patients struggle to pay for high-cost drugs.

PMID- 25939180
TI  - A conversation with Jeff Goldsmith, PhD. Finding success in change.

PMID- 25939181
TI  - Programs for high-need patients. What makes the good ones good?

PMID- 25939182
TI  - Early results out from NIH-sponsored CER study.

PMID- 25939183
TI  - Beneficiaries pay more despite decreased utilization.

PMID- 25939184
TI  - Payment & delivery models, emerging markets affecting medical device industry.

PMID- 25939185
TI  - Two therapies now available for idiopathic pulmonary fibrosis.

PMID- 25939186
TI  - Smaller cost increases for states expanding Medicaid under ACA.

PMID- 25939187
TI  - On ICD-10, the empire strikes back.

PMID- 25939188
TI  - Preference for preferred networks grows along with community pharmacist anger.

PMID- 25939189
TI  - Who'da thunk it? Pharma warms up to FDA taking economics into consideration.

PMID- 25939190
TI  - Can computers 'do no harm'?

PMID- 25939191
TI  - Retail gets some respect.

PMID- 25939192
TI  - Boom times for brain injuries.

PMID- 25939193
TI  - Big and small strides reported in oncology care.

PMID- 25939194
TI  - FDA ponders how to regulate next-generation sequencing.

PMID- 25939195
TI  - Latest weight loss device comes with a hefty price.

PMID- 25939196
TI  - Revisiting the economic efficiencies of observation units.
AB  - BACKGROUND: Recent studies cast doubt about the economic efficiency of
      observation units (OUs). OBJECTIVE: We aimed to reexamine the cost savings of OUs
      compared with inpatient care. METHODS: Claims for 15,851 patients who were
      admitted to inpatient or OUs between January 2009 and December 2012 following
      emergency room (ER) visits for chest pain were retrospectively examined. The two
      groups were compared for total cost of episode, length of stay (LOS), and
      utilization rates of diagnostic procedures, including standard exercise and
      echocardiography stress tests, myocardial perfusion imaging (MPI), coronary
      computed tomography angiography (CCTA), and computed tomography (CT) chest scans.
      Total costs of care and LOS were adjusted for age, gender, risk scores, and
      comorbidities using quantile regression. RESULTS: More than 37% of the sample was
      admitted to inpatient units (n = 5,890) vs 62.7% to OUs (n = 9,961). Patients
      admitted to inpatient units had more comorbidities and longer LOS during their ER
      visit (median 1.5 adjusted days; 10th percentile = 1, 90th percentile = 3) vs.
      median 21 adjusted hours for OUs (20, 23). The adjusted median cost of OUs was
      $5,411 ($4,652, $7,157) vs. $6,946 for inpatient admission ($5,978, $18,683). The
      estimated adjusted cost saving of OUs was $1,535 (95% CI = $1,206, $1,411)
      compared with inpatient admission. About 37% of patients admitted to OUs stayed
      longer than 24 hours. Compared with patients admitted to inpatient units,
      patients in OUs also received more MPI (35.8% vs. 31.5%), CT scans (13.2% vs.
      10.4%), standard exercise test (45.6% vs. 33.8%) and echocardiography stress test
      (8% vs. 3.4%). CONCLUSION: Despite the increased proportion of patients exceeding
      the 24-hour LOS and the increased utilization of advanced imaging procedures, OUs
      are still less costly compared with inpatient admission.

PMID- 25939197
TI  - The new Medicare: quality counts as spending slows.

PMID- 25939198
TI  - Looking forward. ASC calls for its members to safeguard their patients throughout
      the course of surgical treatment.

PMID- 25939199
TI  - Big promise and big challenges for big heath care data.

PMID- 25939200
TI  - State legislatures get back to work.

PMID- 25939201
TI  - The Lancet commission on global surgery makes progress in first year of work: an
      update.

PMID- 25939202
TI  - Profiles in surgical research: Michael T. Longaker, MD, MBA, FACS.

PMID- 25939204
TI  - Surgeons can avoid PQRS and value-based modifier payment penalties.

PMID- 25939203
TI  - ACS and ASE develop simulation-based surgical skills curriculum for medical
      students.

PMID- 25939205
TI  - Expired and expiring ACA provisions.

PMID- 25939206
TI  - Responding to the need for rural general surgery training sites: a how-to.

PMID- 25939207
TI  - Progress in the PROSPECT trial: precision treatment for rectal cancer?

PMID- 25939208
TI  - Where's the fire?

PMID- 25939209
TI  - [The care against barbarism].

PMID- 25939210
TI  - [Should patients receiving immunosuppressive drugs or biotherapies be
      vaccinated?].

PMID- 25939211
TI  - [Borderline lepromatous leprosy].

PMID- 25939212
TI  - [Non invasive prenatal diagnosis of trisomy 21].

PMID- 25939213
TI  - [Autoimmune hepatitis].
AB  - Autoimmune hepatitis is a chronic liver disease characterized by a
      necroinflammatory activity of the portal tract resulting from an immune response
      against hepatocytes. It is relatively rare and its cause is unknown. There are
      three types (I, II and III) associated with the presence of some autoantibodies
      which are not always specific. The diagnosis is based on clinical, biochemical,
      immunological and histological features. The preferred treatment is a combination
      regimen of predniso(lo)ne and azathioprine (budezonide and aziathioprine in when
      cirrhosis is absent). The corticosteroid must be slowly tapered down keeping the
      immunosuppressive agent as maintenance therapy. Drug withdrawal should only be
      considered whether serum transaminases and gamma-globulins level are normal and
      after a normal or near normal liver biopsy.

PMID- 25939214
TI  - [Not Available].

PMID- 25939215
TI  - [Not Available].

PMID- 25939216
TI  - [Venous thromboembolism. A simplified diagnosis and therapeutic advances].

PMID- 25939217
TI  - [Diagnosis of venous thromboembolism].
AB  - The diagnosis of venous thromboembolism relies on the sequential use of
      diagnostic tests, in validated diagnostic algorithms, based on the prior
      assessment of the pretest probability. Main diagnostic tests are D-Dimer and
      lower limb vein compression ultrasonography for deep vein thrombosis; and D
      Dimer, computed tomography pulmonary angiography or lung ventilation perfusion
      scan for pulmonary embolism. These diagnostic strategies allow avoiding the use
      of the historical reference tests for venous thromboembolism, i. e. phlebography
      and pulmo- nary angiography. Several challenges persist, including the diminution
      in the prevalence of the disease among suspected patients, the management of
      small/distal vein thrombosis and pulmonary emboli, and diagnostic strategies in
      special populations, such as elderly patients, pregnant women, and patients with
      a prior episode of venous thromboembolism.

PMID- 25939218
TI  - [Etiologic assessment of venous thromboembolism].
AB  - Venous thromboembolic disease, deep vein thrombosis and pulmoanry embolism is a
      chronic, recurrent multifactorial disease. Cohort studies show that the etiology
      remains unknown in about 50% of cases. Clinical exam is conducted for all cases.
      Systematic complementary exams are of poor information, and paraclinical
      investigation should be limited.

PMID- 25939219
TI  - [Venous thromboembolism during pregnancy].
AB  - Pulmonary embolism is one of the most common cause of maternal death in developed
      countries. Pregnancy is associated with a hypercoagulable state, increased
      especially in patients with thrombophilia. The post-partum period is the period
      carrying the highest risk of venous thromboembolism, especially after caesarean
      delivery. The diagnosis is essential, applying strategies validated in the non
      pregnant population, as none of the diagnostic tests is contra-indicated during
      pregnancy. These strategies use a combination of empirical evaluation of clinical
      probability, D-Dimer measurement. In case of positive D-Dimer testing (or high
      clinical probability), ultrasonography of the legs should be performed first; if
      there is no proximal deep vein thrombosis, pulmonary CT scan or lung scan should
      be performed. Low molecular weight heparin is the treatment of choice until 6
      weeks after the delivery, for a minimal total duration of 6 months. The
      prophylaxis must be individually decided according to histories and risk factors
      of the patient.

PMID- 25939220
TI  - [Initial management of venous thromboembolism].
AB  - The initial management or venous thromboembolism (VTE) corresponds to the first 3
      months of treatment. Pulmonary embolism (PE) are mostly hospitalized. Serious PE
      associated with hemodynamic instability has to be admitted in intensive care unit
      due to the need for fibrinolytics. PE without any risk factor for VTE recurrences
      or death could be followed as outpatient. Conversely, deep vein thrombosis (DVT),
      including proximal DVT are not hospitalized with the xception of patients with
      serious risk factors. The therapeutic strategy is identical between DVT and PE
      treatment with an acute phase with either parenteral anticoagulants, especially
      low molecular weight heparins or fondaparinux, or by an intensive dose of direct
      oral anticoagulant such as rivaroxaban or apixaban. Then maintenance therapy has
      to be prescribed either with vitamin K antagonists with overlapping parenteral
      anticoagulants for at least 72 hours, or with a maintenance dose of apixaban or
      rivaroxaban.

PMID- 25939221
TI  - [Is there still a place for unfractionated heparin in venous thromboembolism?].

PMID- 25939222
TI  - [Evaluation for home treatment of pulmonary embolism].

PMID- 25939223
TI  - [The anticoagulation clinics].

PMID- 25939224
TI  - [Management of superficial vein thrombosis].
AB  - Recent epidemiological studies have highlighted the potential severity of
      superficial vein thrombosis of the lower limbs (SVT). Diagnosis is based on
      clinical and Doppler ultrasonography evaluation, and define its therapeutic
      management. If SVT is associated with objectively confirmed deep vein thrombosis
      or pulmonary embolism, curative anticoagulation is indicated. If SVT is isolated
      and measured over 5 cm long, prophylactic dosage of fondaparinux may be provided
      for 45 days.

PMID- 25939225
TI  - [Long-term treatment of venous thromboembolism].
AB  - Proximal deep venous thrombosis and pulmonary embolism should be treated for at
      least three months. The optimal duration then depends on the cause of venous
      thromboembolism (VTE). When VTE is provoked by a major transient risk factor like
      surgery, three month treatment dura- tion is sufficient. When VTE is provoked by
      a persistent major risk factor like cancer, treatment should be prolonged as long
      as the underlying risk-factor is present. The optimal treatment duration is more
      difficult to define after an episode of unprovoked VTE and when VTE is triggered
      by a minor risk factor like travel or oral contraceptives. In these
      circumstances, the risk of recur- rent VTE is still high after six months of
      anticoagulant treatment. Prolonging the anticoagulant treatment for an additional
      period of 12 to 24 months after the initial period of 6 months is associated with
      delayed recurrences but does not reduce the overall risk of recurrent VTE. In
      these patients, treatment should be stopped at six months or prolonged
      indefinitively according to the risks of recurrence and bleeding of the patient.

PMID- 25939226
TI  - [Thromboembolic pulmonary hypertension].

PMID- 25939227
TI  - [Venous thromboembolism and cancer].
AB  - Venous thromboembolism occurs in up to 10% of patients with cancer. The incidence
      of thrombosis is varying with the nature, the histologic type and the stage of
      the disease. The risk of thrombosis is also increased by most of anticancer
      treatments and supportive care. Although long-term prophylactic treatment is able
      to decrease the rate of venous thromboembolism in patients with cancer, the
      absolute reduction is too low to give long-term prophylaxis, except for some rare
      exceptions. The treatment of cancer associated thrombosis is based on the use of
      low-molecular weight heparin for at least three to six months. In most cases,
      anticoagulation should be given for a longer period but the choice of the drug
      should be indi- vidualized on the basis of the evolution of the underlying
      cancer, overall prognosis, tolerance of injections and patient's preference.
      Recurrent venous thromboembolism during treatment with low-molecular weight
      heparin can be treated with a 10% dose escalation. Dose should be adjusted during
      periods of thrombocytopenia. Finally, the direct oral anticoagulants have not
      been compared with low-molecular weight heparins for the treatment of cancer
      associated thrombosis.

PMID- 25939228
TI  - [Acute psychotic disorders are a psychiatric emergency].

PMID- 25939229
TI  - [Acute hallucinatory psychosis].
AB  - The concept of acute delirious puff refers to a transient psychotic state
      characterized by the sudden outbreak of a polymorphic delusional state in its
      themes and mecha- nisms. Magnan, in the late of nineteenth century, insti- gated
      the initial description of this concept. Rediscovered by Henri EY, it's current
      presence in the French psychiatry despite various attempts to dismantle it
      results from a singularity based on five cardinal points: it affects young
      adults, its onset is sudden, delusions are polymorphic and not systematic, there
      is a marked emotional lability and access is rapidly cured. This entity reveals
      vulnerability and must be understood carefully by the general practitioner, the
      issue being the prevention of progression to chronic psychosis.

PMID- 25939230
TI  - [Acute substance-induced psychotic disorder].
AB  - An acute substance induced psychotic disorder is a cause to raise with a state of
      agitation in an acute delusional clinical setting. Patients are most often seen
      in hospital emergency rooms. Rapid diagnosis must be made. An integrated
      therapeutic management should be considered. Both psychiatric and addiction
      problems must be taken into account.

PMID- 25939231
TI  - [Post-partum psychosis].
AB  - Postpartum psychosis occurs in 1-2/1000 childbearing women. It is commonly
      admitted that it belongs to bipolar disorder with psychotic features. A strong
      link between puerperal psychosis and bipolar disorder has been established.
      Symptoms include rapid mood fluctuations, confusion, delusions, hallucinations
      and bizarre behaviour. It can lead to devastating consequences. It is a
      psychiatric emergency that requires an urgent evaluation to exclude any organic
      cause. Therefore, early identification and appropriate treatment are critical. A
      quick and effective relief is necessary for maternal and child health and mother
      infant relationship. Perinatal health professionals have to be accurate screening
      postpartum psychosis symptoms and have to educate patients and their family.

PMID- 25939232
TI  - [Acute delirium in decompensated schizophrenia and bipolar disorder].
AB  - Acute delirium is common in decompensated schizophrenia and bipolar disor- der:
      more 50% in two years after the first episode of schizophrenia and 90% of
      patients with a diagnosis of bipolar disorder. Early signs precede in more 50% of
      cases the delirious exacerbation of 6 months. These non-specific signs are a
      change in the mood, an increase of anxiety, sleep and food disorders and suicidal
      ideation. After this prodromal phase, a persecutory delusion and hallucinations
      are often present in decompensated schizophrenia. In decompensated bipolar
      disorder, the delusional syndrome is congruent with the mood. The care should be
      the earliest possible. The treatment by antipsychotic or mood stabilizer must be
      increased or re-introduced and maintained during a long time in order to prevent
      a relapse. In parallel, a psychosocial care must be instituted.

PMID- 25939233
TI  - [Organic delusional states].

PMID- 25939234
TI  - [Delusional disorders].
AB  - Delusional disorders are divided in French nosography into three clinical disease
      entities: paranoid delusions, psychose hallucinatoire chronique, and paraphrenia.
      Their common characteristics are a late start, a chronic evolution, no cognitive
      impairment and no dissociation. Delusio- nal syndrome is often at the forefront
      with a predominant mechanism characterizing each disorder (interpretation for
      paranoid delusions, hallucination for psychose hallucinatoire chronique and
      imagination for paraphrenia). Although these disorders are less sensitive to the
      medication than schizophrenia, care is based on second generation antipsychotic
      treatment, in association with psychotherapy and social care. The aim of
      treatment is to alleviate delusion intensity to improve global functioning and to
      prevent violent incidents or suicide attempt.

PMID- 25939235
TI  - [Current data on antipsychotics].

PMID- 25939236
TI  - [Quality measures: sure ... but].

PMID- 25939237
TI  - [Treatment of hepatitis C: decisive therapeutic advances].

PMID- 25939238
TI  - [Prolonged fever: special situations that modify the diagnostic approach].

PMID- 25939239
TI  - [What is a blister?].

PMID- 25939240
TI  - [Viral hepatitis].

PMID- 25939241
TI  - [Prolonged fever].

PMID- 25939242
TI  - [Bullous disorders affecting the skin and/or external mucosa].

PMID- 25939243
TI  - [When accidents multiplied on trawlers and tuna fishing vessels].

PMID- 25939244
TI  - Can the critically ill consent to participation in commercial television
      programmes? An Australian prehospital and emergency medicine perspective.
AB  - The fly-on-the-wall medical documentary is a popular television phenomenon. When
      patients can give appropriate consent to filming, the final product can be both
      educational for the public and rewarding for its subjects. However, in the
      dynamic world of emergency and prehospital medicine, consenting critically ill
      patients before filming is a significant challenge. The main barriers to gaining
      valid consent in the field and in the ED are limited time to inform the patient
      and the diminished capacity of the sick patient. Although there is an argument
      that involvement in a commercial film might be beneficial to several parties,
      including the patient, these benefits do not amount to therapeutic necessity if
      prior consent is not obtainable. Despite this, we still see acutely incapacitated
      patients featured in some television programmes. In these cases, the conventional
      process of consent might be being sidestepped in order to obtain permission for
      broadcast retrospectively. This alternative process fails to recognise that
      incapacitated patients require protection from an invasion of privacy that occurs
      when a crew is filming their resuscitations. This harm has already occurred by
      the time consent is sought. Ultimate responsibility for defending the patients'
      interests during their medical treatment rests with the medical practitioner. We
      argue that filming a patient without prior consent in both the prehospital and
      emergency environment is ethically unsound: it threatens trust in the healthcare
      relationship and might compromise the patient's dignity and privacy. Robust
      guidelines should be developed for all healthcare professionals who engage with
      commercial film crews. 

PMID- 25939245
TI  - Cardiac-specific disruption of Bin1 in mice enables a model of stress- and age
      associated dilated cardiomyopathy.
AB  - Non-compensated dilated cardiomyopathy (DCM) leading to death from heart failure
      is rising rapidly in developed countries due to aging demographics, and there is
      a need for informative preclinical models to guide the development of effective
      therapeutic strategies to prevent or delay disease onset. In this study, we
      describe a novel model of heart failure based on cardiac-specific deletion of the
      prototypical mammalian BAR adapter-encoding gene Bin1, a modifier of age
      associated disease. Bin1 deletion during embryonic development causes
      hypertrophic cardiomyopathy and neonatal lethality, but there is little
      information on how Bin1 affects cardiac function in adult animals. Here we report
      that cardiomyocyte-specific loss of Bin1 causes age-associated dilated
      cardiomyopathy (DCM) beginning by 8-10 months of age. Echocardiographic analysis
      showed that Bin1 loss caused a 45% reduction in ejection fraction during aging.
      Younger animals rapidly developed DCM if cardiac pressure overload was created by
      transverse aortic constriction. Heterozygotes exhibited an intermediate phenotype
      indicating Bin1 is haplo-insufficient to sustain normal heart function. Bin1 loss
      increased left ventricle (LV) volume and diameter during aging, but it did not
      alter LV volume or diameter in hearts from heterozygous mice nor did it affect LV
      mass. Bin1 loss increased interstitial fibrosis and mislocalization of the
      voltage-dependent calcium channel Cav 1.2, and the lipid raft scaffold protein
      caveolin-3, which normally complexes with Bin1 and Cav 1.2 in cardiomyocyte
      membranes. Our findings show how cardiac deficiency in Bin1 function causes age-
      and stress-associated heart failure, and they establish a new preclinical model
      of this terminal cardiac disease.

PMID- 25939246
TI  - What keeps nurses busy in the mental health setting?
AB  - ACCESSIBLE SUMMARY: Recent evidence suggests that the interactional work of
      mental health nursing has been eroded and redirected to the task-based roles of
      medicine. This study utilized work sampling methodology to observe the proportion
      of time nurses working in a mental health setting spend in direct care, indirect
      care and service-related activities. Nurses spent 32% of their time in direct
      care, 52% in indirect care and 17% in service-related activities. Mental health
      nurses need to re-establish their therapeutic availability to maximize consumer
      experiences and outcomes. ABSTRACT: The foundation of mental health nursing has
      historically been grounded in an interpersonal, person-centred process of health
      care, yet recent evidence suggests that the interactional work of mental health
      nursing is being eroded. Literature emphasizes the importance of person-centred
      care on consumer outcomes, a model reliant upon the intimate engagement of nurses
      and consumers. Yet, the arrival of medical interventions in psychiatry has
      diverted nursing work from the therapeutic nursing role to task-based roles
      delegated by medicine, distancing nurses from consumers. This study used work
      sampling methodology to observe the proportion of time nurses working in an
      inpatient mental health setting spend in the activities of direct care, indirect
      care and service-related activities. Nurses spent 32 of their time in direct
      care, 52% in indirect care and 17% in service-related activities. Mental health
      nurses need to re-establish their therapeutic availability to maximize consumer
      experiences and outcomes.

PMID- 25939247
TI  - Detection and molecular characterisation of Giardia duodenalis, Cryptosporidium
      spp. and Entamoeba spp. among patients with gastrointestinal symptoms in Gambo
      Hospital, Oromia Region, southern Ethiopia.
AB  - OBJECTIVES: To assess the prevalence and genetic diversity of the enteric
      protozoa species G. duodenalis, Cryptosporidium spp. and Entamoeba histolytica in
      individuals with gastrointestinal symptoms compatible with infections by these
      pathogens seeking medical attention in a rural area in southern Ethiopia.
      METHODS: A total of 92 stool samples were initially screened by direct microscopy
      and immunochromatography and further confirmed by molecular methods. G.
      duodenalis-positive samples were molecularly characterised by multilocus
      genotyping of the glutamate dehydrogenase and beta-giardin genes of the parasite.
      PCR and DNA sequence analysis of the gene encoding the 60-kDa glycoprotein was
      used for the subtyping of Cryptosporidium isolates. Detection and differential
      diagnosis of E. histolytica/dispar were conducted by real-time PCR. RESULTS: PCR
      based prevalences were 10.9% for G. duodenalis, 1.1% for Cryptosporidium spp. and
      3.3% for Entamoeba spp. Seven (four novel and three known) subtypes of G.
      duodenalis assemblage B were identified at the GDH locus and 5 (one novel and
      four known) at the BG locus. A novel variant of C. hominis subtype IbA9G3 was
      also identified. Two Entamoeba isolates were assigned to E. dispar and an
      additional one to E. histolytica. CONCLUSION: Although preliminary, our results
      strongly suggest that giardiasis, cryptosporidiosis and amoebiasis represent a
      significant burden in Ethiopian rural population.

PMID- 25939248
TI  - Nomenclature for factors of the HLA system, update January 2015.

PMID- 25939249
TI  - A Four-Year Follow-up Study of Renal Epithelioid Angiomyolipoma: A Multi-Center
      Experience and Literature Review.
AB  - In this study, we systematically explored the clinical manifestations, diagnosis,
      treatment, and prognosis of renal epithelioid angiomyolipoma (EAML)
      retrospectively by analyzing data of 52 patients diagnosed with EAML at four
      centers. Our results showed that the onset of EAML was usually inconspicuous, and
      so no obvious symptoms or signs had occurred in most patients at diagnosis. Its
      diagnoses always depended on postoperative pathological examination. The
      immunohistochemical (IHC) results [HMB45 ( + ), cytokeratin (-), and S100 (-)]
      could be used to differentiate EAML from other malignancies such as renal cell
      cancer (RCC) and sarcomas. For treatment, surgery resulted in satisfactory short
      term prognosis. The long-term prognosis of patients with EAML was poor,
      particularly when a large size, a high percentage of epithelioid component, tumor
      thrombus formation, and necrosis were present. In conclusion, EAML is a tumor
      with malignant potential. Once diagnosed, integrated approaches, including
      surgery, chemotherapy, and targeted therapy, should be considered; a close follow
      up regimen is necessary for cases that met: 1) tumor size>9 cm, 2) tumor thrombus
      formation in the vein, 3) epithelioid cells>70% or atypia cells>60%, and 4)
      necrosis.

PMID- 25939250
TI  - A mechanistic study of Pd(OAc)2-catalyzed intramolecular C-H functionalization
      reaction involving CO/isonitrile insertion.
AB  - The mechanism of the Pd(OAc)2-catalyzed intramolecular C-H functionalization
      reaction involving CO/isonitrile insertion was investigated with the aid of
      density functional theory calculations at the B3LYP level. The similarity between
      the CO and isonitrile systems includes the following: (1) the anagostic bonding
      mechanism rather than the concerted metallation-deprotonation (CMD) mechanism is
      operative for the C-H cleavage step, (2) the CO/isonitrile insertion step is rate
      determining, and (3) the C-H activation and CO/isonitrile insertion steps are
      accomplished with Pd(II) and Pd(III), respectively. For the reaction including
      isonitrile insertion, the arene C-H activation step occurs after deprotonation of
      the imino group. However, for reaction including CO insertion, the arene C-H
      activation step is the first step of the reaction mechanism. The difference
      between CO and isonitrile systems in the reaction mechanism can be attributed to
      the difference in the oxidants used. In the reaction including isonitrile
      insertion, the high endergonicity of the oxidation step suppresses prior C-H
      activation and favors prior deprotonation of the imino group. In the reactions
      including CO insertion, the low endergonicity of the oxidation step allows prior
      C-H activation to occur.

PMID- 25939251
TI  - High-glucose-cultivated peripheral blood mononuclear cells impaired keratinocyte
      function via reduced IL-22 expression: implications on impaired diabetic wound
      healing.

PMID- 25939252
TI  - CT before transcatheter aortic valve replacement: Value of venous phase imaging
      for detection and interpretation of findings with impact on the TAVR procedure.
AB  - BACKGROUND: Multidetector CT (MDCT) is performed to evaluate patients before
      transcatheter aortic valve replacement (TAVR). MDCT can uncover relevant
      nonvascular incidental findings. The use of venous phase imaging (VPI) in MDCT
      before TAVR has not been evaluated. OBJECTIVE: To evaluate the incidence of
      nonvascular findings in MDCT before TAVR with effect on the TAVR procedure and
      the value of VPI in this setting. METHODS: Sixty-four-slice MDCT angiography with
      VPI (100 mL contrast agent with 370-mg iopromide per mL) in 76 patients was
      retrospectively evaluated by 2 readers. Nonvascular findings were separately
      assessed on arterial and venous phase images and categorized in consensus as
      nonsignificant (no effect on TAVR), intermediate (further workup or surveillance
      necessary, no effect on TAVR), or significant (effect on TAVR). Radiation dose
      was recorded as dose-length product (DLP) and effective dose was calculated.
      RESULTS: A total of 169 findings were detected, of which 155 (91.7%) were
      nonsignificant, 13 (7.7%) were intermediate, and 1 (0.6%) was significant. TAVR
      was canceled in 1 patient (1.3%) because of suspected pancreatic cancer. No
      significant finding was seen on VPI only. Mean total DLP was 1137.9 mGy.cm (16.07
      mSv) and the proportional mean DLP of VPI was 403 mGy.cm (6.85 mSv). CONCLUSION:
      The incidence of nonvascular significant findings in MDCT before TAVR is low and
      VPI in our series did not add value. However, it may be considered in selected
      patients.

PMID- 25939253
TI  - Quantification of glypican 3, beta-catenin and claudin-1 protein expression in
      hepatoblastoma and paediatric hepatocellular carcinoma by colour deconvolution.
AB  - AIMS: To identify an immunohistochemical panel for paediatric malignant
      epithelial liver tumours. METHODS AND RESULTS: Forty-five hepatoblastomas (HBs),
      13 paediatric hepatocellular carcinomas (HCCs) and two hepatocellular malignant
      neoplasms not otherwise specified (NOS) were chosen for immunohistochemical
      staining of glypican 3 (GPC3), beta-catenin, claudin-1, delta-like protein (DLK),
      and forkhead box protein G1 (FOXG1). Immunostaining was quantitatively analysed
      with NIH imagej software coupled with colour deconvolution. Different subtypes of
      HB and HCC showed distinct staining patterns of GPC3, beta-catenin, and claudin
      1. Moreover, GPC3, beta-catenin and claudin-1 all showed higher expression in
      classic HCC and embryonal HB than in fetal HB; GPC3 showed complete negativity in
      small-cell undifferentiated (SCU) HB and fibrolamellar HCC (FLC); beta-catenin
      showed the strongest expression in SCU HB but the weakest expression in FLC. A
      panel of these three immunomarkers was useful for the diagnosis of hepatocellular
      malignant neoplasms NOS. The expression of DLK and FOXG1 was inconstant among
      fetal and embryonal HB and classic HCC. CONCLUSIONS: A panel of GPC3, beta
      catenin and claudin-1 is helpful for differentiating HB subtypes and
      distinguishing HB from HCC.

PMID- 25939254
TI  - Are predictors of making a quit attempt the same as predictors of 3-month
      abstinence from smoking? Findings from a sample of smokers recruited for a study
      of computer-tailored smoking cessation advice in primary care.
AB  - AIMS: To identify predictors of quit attempts and of 3-month abstinence from
      cigarette smoking. DESIGN: Secondary analysis of data gathered for a two-armed
      randomized controlled trial with 6-month follow-up. SETTING: A total of 123
      general practices across the United Kingdom. PARTICIPANTS: A total of 4397
      participants who completed the 6-month follow-up. Participants were categorized
      on self-reported smoking behaviour at 6-month follow-up as non-attempters (n =
      2664), attempted quitters (n = 1548) and successful quitters (n = 185). MEASURES:
      Demographic characteristics, smoking history and nicotine dependence, cognitive
      and social-environmental factors measured at baseline were examined as potential
      predictors of quit attempts and 3-month abstinence. FINDINGS: Univariate
      predictors of quit attempts included commitment [odds ratio (OR) = 11.64, 95%
      confidence interval (CI) = 8.30-16.32], motivation (OR = 2.10, 95% CI = 1.98
      2.22) and determination to quit (OR = 1.94, 95% CI = 1.83-2.05). Successful
      quitting was associated with being married (OR = 1.51, 95% CI = 1.11-2.05), lower
      social deprivation (OR = 0.47, 95% CI = 0.30-0.74), higher reading level (OR =
      1.62, 95% CI = 1.19-2.21) and lower nicotine dependence (OR = 0.42, 95% CI = 0.29
      0.62). Health problems related to smoking and previous quit attempts for 3 months
      or longer predicted both. In the multivariate analysis, the significant
      predictors of making a quit attempt were; later stage of readiness to quit (OR =
      5.38, 95% CI = 3.67-7.89), motivation (OR = 1.48, 95% CI = 1.34-1.62) and
      determination to quit (OR = 1.16, 95% CI = 1.05-1.29) and health problems related
      to smoking (OR = 1.44, 95% CI = 1.18-1.75). For 3-month abstinence, the only
      significant predictor was not having health problems related to smoking (OR =
      0.50, 95% CI = 0.29-0.83). CONCLUSIONS: While high motivation and determination
      to quit is necessary to prompt an attempt to quit smoking, demographic factors
      and level of nicotine dependence are more important for maintaining abstinence.

PMID- 25939255
TI  - Distribution of veterinarians and animals in Australia.

PMID- 25939256
TI  - RE: Modelling foot-and-mouth disease transmission in a wild pig-domestic cattle
      ecosystem.

PMID- 25939257
TI  - Michael Harrison OAM: 1942-2015.

PMID- 25939258
TI  - Spatial and temporal evaluation of veterinarians and veterinary employers
      relative to human and domesticated animal populations in Australia 2002-2012.
AB  - OBJECTIVES: To examine the distribution of veterinarians, humans, domestic
      animals and non-private practice employers in Australia and assess whether a
      relationship exists between them. To identify trends in the number of
      veterinarians, humans and domestic animals between 2002 and 2012 that may
      influence future demands for veterinary services. METHODS: Australian data on
      registered veterinarians, veterinary practices, the human population and various
      domestic animal species were obtained for the years 2002, 2007 and 2012. The data
      were mapped to assess distribution and temporal trends in number and distribution
      were assessed. RESULTS: Nationally, registered veterinarians were distributed
      similarly to the general population, with a slight bias to regional areas. The
      number of veterinarians nationally increased both in absolute terms and relative
      to the human population between 2002 and 2012. Companion animals were distributed
      similarly to the human population and livestock occurred in highest density in
      the more productive agricultural areas. The areas with highest density of
      domestic animals were within 100 km of an existing veterinary practice. There was
      moderate correlation between the number of registered veterinarians and the
      number of people or companion animals, but poor correlation for livestock. The
      number of domestic animal species decreased between 2002 and 2012, with the
      exceptions of cattle and poultry. CONCLUSIONS: There is not a simple relationship
      between the number of veterinarians, people or domestic animals. Better data are
      needed to describe the drivers for demand for veterinary services and enable
      future workforce planning.

PMID- 25939259
TI  - Owned dog and cat populations in remote Indigenous communities in the Northern
      Territory: a retrospective study.
AB  - OBJECTIVE: To determine the population of owned dogs and cats in Indigenous
      communities in the Northern Territory (NT), and compare the data with those for
      the average Australian household. METHODS: Results of 20 Indigenous community
      animal health programs were analysed for species present and dog and cat numbers.
      The female breeding and puppy populations were also identified. RESULTS: The
      average dog population density was significantly higher than the average
      Australian household, with an average of 24.4 dogs per 10 households, but the
      average cat population density was similar (3.3 cats per 10 households). Numbers
      of other species were not determined. The average percentage of puppies in these
      communities was 17.6% of the treated canine population, the average percentage of
      breeding canine females was 18.6% of the treated canine population, and the
      average percentage of breeding feline females was 19.7% of the total feline
      population. CONCLUSIONS: Dog populations in NT Indigenous communities were at
      least 6.3-fold higher per household compared with data for the rest of Australia.
      Cat populations per household were similar to the overall population. Factors
      contributing to the relatively high dog populations in remote Indigenous
      communities include a lack of veterinary presence, community remoteness, poor
      socioeconomic factors, poor house and yard designs, cultural reasons, communal
      beliefs, lack of community animal management and a lack of funding. We believe
      that animal health programs are an important way of addressing a number of these
      issues. Other elements that should be addressed include improving house and yard
      design, increasing education regarding animal health, care and welfare, and
      increasing the training and presence of health and animal professionals.

PMID- 25939260
TI  - John Michael Bourke AM: 1932-2015.

PMID- 25939261
TI  - Retrospective survey of bronchoalveolar lavage fluid cytology in Western
      Australian horses presented for evaluation of the respiratory tract: effect of
      season on relative cell percentages.
AB  - OBJECTIVE: To characterise the cytological changes in equine bronchoalveolar
      lavage (BAL) samples over multiple years to determine if the prevalence of a
      relative mast cell response was influenced by season. METHODS: Medical records of
      228 horses with clinical signs consistent with non-infectious respiratory disease
      or poor performance where a BAL was performed were reviewed retrospectively. BAL
      fluid cytology and categorised clinical variables were analysed using a Chi
      square test to determine associations. RESULTS: The predominant signalment was a
      racing horse between 2 and 6 years of age, and poor athletic performance was the
      most common presenting complaint. Based on published criteria, 69.7% of horses
      had abnormal BAL cytology. The presence of nasal discharge was the only clinical
      finding that differed significantly between horses with abnormal and normal
      cytology. The most common cytological derangement was a mixed cell response
      (26.7%), the majority of which comprised elevated percentages of neutrophils and
      mast cells. A solely neutrophilic response or mast cell response occurred with
      equal frequency (18% and 18.95%, respectively), and an isolated eosinophilic
      response was noted in 6.1% of cases. Of the horses with cytology consistent with
      non-infectious lower airway inflammation, 58.4% had increases in the relative
      percentage of mast cells. Cell profiles were significantly associated with
      season, with mastocytosis occurring more commonly in spring, whereas eosinophilic
      and neutrophilic responses were more common in summer. CONCLUSION: In this study,
      a relative mast cell increase was the most common cytological profile in horses
      with lower airway inflammation and was associated with season.

PMID- 25939262
TI  - Survey of farmer knowledge and attitudes to endemic disease management in South
      Australia, with a focus on bovine viral diarrhoea (bovine pestivirus).
AB  - OBJECTIVE: We aimed to establish the attitudes of South Australian cattle farmers
      towards endemic animal disease prevention and control, with a particular focus on
      the awareness of and attitudes towards bovine viral diarrhoea (BVD). METHODS:
      This cross-sectional postal survey involved mailing a questionnaire to all South
      Australian cattle owners with 35 or more head of cattle. RESULTS: Worms and lice
      were the most common animal disease concerns. Less than half of responding
      farmers were adequately vaccinating their herds against clostridial diseases, but
      53.0% stated that they utilised quarantine procedures. Less than 20% of
      respondents had actively taken part in BVD educational opportunities, or had
      vaccinated or tested their herd for BVD; less than 20% of respondents were
      actively involved in any systematic control of Johne's disease. Overall, farmers'
      actual knowledge of BVD was lower than their perceived understanding, although
      their interest in BVD and its control was high. CONCLUSIONS: Disease prevention
      measures such as vaccination, quarantine and participation in systematic control
      schemes were used by a minority of respondents. The results suggest that
      respondents acknowledge BVD as an important and relevant disease, despite many
      believing it was not a problem in their herd. Interest in BVD appears to be high
      and it is likely that an education program would be well received.

PMID- 25939263
TI  - Comparison of analgesic and systemic effects of bupivacaine, methadone, or
      bupivacaine/methadone administered epidurally in conscious sheep.
AB  - OBJECTIVE: The aim of this study was to evaluate the combination of bupivacaine
      and methadone administered epidurally in sheep. METHODS: Six healthy female mixed
      breed sheep weighing 35-46 kg and aged 12-18 months were included. Each sheep was
      assigned to receive three treatments: 0.5 mg/kg 0.25% bupivacaine (BP), 0.3 mg/kg
      1% methadone (MT) or 0.25 mg/kg bupivacaine and 0.15 mg/kg methadone (BPMT). All
      drugs were injected into the lumbosacral space through an epidural catheter. Each
      animal received each treatment at random. Heart rate, arterial blood pressure
      (systolic, diastolic and mean), respiratory rate, rectal temperature, analgesia,
      sedation and motor block were determined before treatment and at predetermined
      intervals. RESULTS: The duration of analgesia was 240, 220, and 180 min for BP,
      MT and BPMT, respectively (P < 0.05). Motor block for all agents was mild to
      moderate. None or the treatments significantly altered the heart rate, blood
      pressure or respiratory rate. CONCLUSION: Our findings suggest that lumbosacral
      epidural administration of bupivacaine, methadone or a combination of the two
      drugs can provide perioperative analgesia in sheep as part of their management
      for surgical procedures in the flank and hindlimbs.

PMID- 25939264
TI  - Isolation of Nocardia mexicana from focal proliferative tenosynovitis and
      arthritis in a steer.
AB  - CASE REPORT: An 18-month-old Charolais steer was presented with lameness and
      fluctuant swelling of the right stifle joint, which yielded neutrophils on fine
      needle aspiration. A diagnosis of bacterial proliferative tenosynovitis and
      arthritis was made on postmortem and histological examination. Culture and 16S
      rRNA sequencing identified a Nocardia sp. with 99% homology with the
      corresponding DNA fragment of N. mexicana DSM 44952. Antimicrobial susceptibility
      testing revealed the isolate was susceptible to co-trimoxazole and third
      generation cephalosporins. CONCLUSION: We report the first case, both in
      Australia and internationally, of proliferative tenosynovitis and arthritis
      caused by Nocardia spp. infection in a bovine and the first report of pathology
      attributed to N. mexicana in a veterinary patient. Given the limited
      susceptibility of the bacteria, the poor antimicrobial penetration that would be
      expected and the morphological changes that had taken place in the joint; the
      steer would have required protracted antimicrobial treatment in addition to
      invasive debridement of the lesion. This case emphasises the importance of
      routinely performing cytology and extended incubation of cultures in cases of
      arthritis in order to make ethical and economically viable treatment decisions.

PMID- 25939265
TI  - Victor Wallace Smith: 1926-2014.

PMID- 25939266
TI  - An outbreak of primary photosensitisation in lambs secondary to consumption of
      Biserrula pelecinus (biserrula).
AB  - CASE REPORT: An outbreak of photosensitisation affecting approximately 25% of a
      flock of 120 meat lambs that was grazing a monoculture of the pasture legume
      Biserrula pelecinus var. Casbah (biserrula) was investigated. Blood samples were
      taken from sheep with moderate to severe clinical signs, and from apparently
      normal animals, for a complete blood count and biochemistry; 5 affected animals
      were subjected to a full necropsy. Histopathological investigation showed lesions
      consistent with photosensitisation of the exposed unpigmented skin of the face
      and ears. No histopathological or clinical pathological abnormalities suggestive
      of a hepatopathy were detected in any of the cases, indicating that the lesions
      observed in this flock were caused by a primary photosensitising agent present in
      B. pelecinus. CONCLUSION: This is the first confirmation that photosensitisation
      caused by ingestion of biserrula is caused by a primary photosensitising agent.

PMID- 25939267
TI  - Animal cruelty and reporting.

PMID- 25939270
TI  - Changes in northern Gulf of Mexico sediment bacterial and archaeal communities
      exposed to hypoxia.
AB  - Biogeochemical changes in marine sediments during coastal water hypoxia are well
      described, but less is known about underlying changes in microbial communities.
      Bacterial and archaeal communities in Louisiana continental shelf (LCS) hypoxic
      zone sediments were characterized by pyrosequencing 16S rRNA V4-region gene
      fragments obtained by PCR amplification of community genomic DNA with bacterial-
      or archaeal-specific primers. Duplicate LCS sediment cores collected during
      hypoxia had higher concentrations of Fe(II), and dissolved inorganic carbon,
      phosphate, and ammonium than cores collected when overlying water oxygen
      concentrations were normal. Pyrosequencing yielded 158,686 bacterial and 225,591
      archaeal sequences from 20 sediment samples, representing five 2-cm depth
      intervals in the duplicate cores. Bacterial communities grouped by sampling date
      and sediment depth in a neighbor-joining analysis using Chao-Jaccard shared
      species values. Redundancy analysis indicated that variance in bacterial
      communities was mainly associated with differences in sediment chemistry between
      oxic and hypoxic water column conditions. Gammaproteobacteria (26.5%) were most
      prominent among bacterial sequences, followed by Firmicutes (9.6%), and
      Alphaproteobacteria (5.6%). Crenarchaeotal, thaumarchaeotal, and euryarchaeotal
      lineages accounted for 57%, 27%, and 16% of archaeal sequences, respectively. In
      Thaumarchaeota Marine Group I, sequences were 96-99% identical to the
      Nitrosopumilus maritimus SCM1 sequence, were highest in surficial sediments, and
      accounted for 31% of archaeal sequences when waters were normoxic vs. 13% of
      archaeal sequences when waters were hypoxic. Redundancy analysis showed
      Nitrosopumilus-related sequence abundance was correlated with high solid-phase
      Fe(III) concentrations, whereas most of the remaining archaeal clusters were not.
      In contrast, crenarchaeotal sequences were from phylogenetically diverse
      lineages, differed little in relative abundance between sampling times, and
      increased to high relative abundance with sediment depth. These results provide
      further evidence that marine sediment microbial community composition can be
      structured according to sediment chemistry and suggest the expansion of hypoxia
      in coastal waters may alter sediment microbial communities involved in carbon and
      nitrogen cycling.

PMID- 25939271
TI  - Dynamic assembly of polymer nanotube networks via kinesin powered microtubule
      filaments.
AB  - We describe for the first time how biological nanomotors may be used to actively
      self-assemble mesoscale networks composed of diblock copolymer nanotubes. The
      collective force generated by multiple kinesin nanomotors acting on a microtubule
      filament is large enough to overcome the energy barrier required to extract
      nanotubes from polymer vesicles comprised of poly(ethylene oxide-b-butadiene) in
      spite of the higher force requirements relative to extracting nanotubes from
      lipid vesicles. Nevertheless, large-scale polymer networks were dynamically
      assembled by the motors. These networks displayed enhanced robustness, persisting
      more than 24 h post-assembly (compared to 4-5 h for corresponding lipid
      networks). The transport of materials in and on the polymer membranes differs
      substantially from the transport on analogous lipid networks. Specifically, our
      data suggest that polymer mobility in nanotubular structures is considerably
      different from planar or 3D structures, and is stunted by 1D confinement of the
      polymer subunits. Moreover, quantum dots adsorbed onto polymer nanotubes are
      completely immobile, which is related to this 1D confinement effect and is in
      stark contrast to the highly fluid transport observed on lipid tubules. 

PMID- 25939272
TI  - Neuromuscular disease: Improved diagnostic sensitivity can aid the correct choice
      of treatment for patients with myasthenia gravis.

PMID- 25939269
TI  - Deletion of myosin VI causes slow retinal optic neuropathy and age-related
      macular degeneration (AMD)-relevant retinal phenotype.
AB  - The unconventional myosin VI, a member of the actin-based motor protein family of
      myosins, is expressed in the retina. Its deletion was previously shown to reduce
      amplitudes of the a- and b-waves of the electroretinogram. Analyzing wild-type
      and myosin VI-deficient Snell's Waltzer mice in more detail, the expression
      pattern of myosin VI in retinal pigment epithelium, outer limiting membrane, and
      outer plexiform layer could be linked with differential progressing ocular
      deficits. These encompassed reduced a-waves and b-waves and disturbed oscillatory
      potentials in the electroretinogram, photoreceptor cell death, retinal microglia
      infiltration, and formation of basal laminar deposits. A phenotype comprising
      features of glaucoma (neurodegeneration) and age-related macular degeneration
      could thus be uncovered that suggests dysfunction of myosin VI and its variable
      cargo adaptor proteins for membrane sorting and autophagy, as possible candidate
      mediators for both disease forms. 

PMID- 25939268
TI  - Natural killer cell heterogeneity: cellular dysfunction and significance in HIV-1
      immuno-pathogenesis.
AB  - Natural killer (NK) cells are innate immune effectors that provide first line of
      defence against viruses. Human NK cells are heterogeneous in nature, and their
      functions rely on a dynamic balance between germ-line-encoded activating and
      inhibitory receptors. HIV-1 infection results in altered NK cell receptor
      repertoire and impaired effector functions including the ability to lyse virus
      infected cells and secretion of antiviral cytokine IFN-gamma. Over the last
      decade, additional NK cell subset-specific molecules have been identified,
      leading to emergence of a more complex cellular diversity than previously
      thought. Herein, we discuss NK cell subset redistribution, altered receptor
      repertoire and influence of interaction of polymorphic leucocyte antigen (HLA)
      and killer cell immunoglobulin-like receptors (KIR) on HIV-1 disease progression.

PMID- 25939273
TI  - Neuro-oncology: Primary CNS lymphoma treatment--the devil is in the details.

PMID- 25939275
TI  - Backbone, side chain and heme resonance assignments of cytochrome OmcF from
      Geobacter sulfurreducens.
AB  - Gene knockout studies on Geobacter sulfurreducens (Gs) cells showed that the
      outer membrane cytochrome OmcF is involved in respiratory pathways leading to the
      extracellular reduction of Fe(III) citrate and U(VI) oxide. In addition,
      microarray analysis of OmcF-deficient mutant versus the wild-type strain revealed
      that many of the genes with decreased transcript level were those whose
      expression is upregulated in cells grown with a graphite electrode as electron
      acceptor. This suggests that OmcF also regulates the electron transfer to
      electrode surfaces and the concomitant electrical current production by Gs in
      microbial fuel cells. Extracellular electron transfer processes (EET) constitute
      nowadays the foundations to develop biotechnological applications in biofuel
      production, bioremediation and bioenergy. Therefore, the structural
      characterization of OmcF is a fundamental step to understand the mechanisms
      underlying EET. Here, we report the complete assignment of the heme proton
      signals together with (1)H, (13)C and (15)N backbone and side chain assignments
      of the OmcF, excluding the hydrophobic residues of the N-terminal predicted lipid
      anchor. 

PMID- 25939274
TI  - FTD and ALS--translating mouse studies into clinical trials.
AB  - Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are related
      neurodegenerative disorders, which are characterized by a rapid decline in
      cognitive and motor functions, and short survival. Although the clinical and
      neuropathological characterization of these diseases has progressed--in part-
      through animal studies of pathogenetic mechanisms, the translation of findings
      from rodent models to clinical practice has generally not been successful. This
      article discusses the gap between preclinical animal studies in mice and clinical
      trials in patients with FTD or ALS. We outline how to better design preclinical
      studies, and present strategies to improve mouse models to overcome the
      translational shortfall. This new approach could help identify drugs that are
      more likely to achieve a therapeutic benefit for patients.

PMID- 25939276
TI  - Rouse mode analysis of chain relaxation in polymer nanocomposites.
AB  - Large-scale molecular dynamics simulations are used to study the internal
      relaxations of chains in nanoparticle (NP)/polymer composites. We examine the
      Rouse modes of the chains, a quantity that is closest in spirit to the self
      intermediate scattering function, typically determined in an (incoherent)
      inelastic neutron scattering experiment. Our simulations show that for weakly
      interacting mixtures of NPs and polymers, the effective monomeric relaxation
      rates are faster than in a neat melt when the NPs are smaller than the
      entanglement mesh size. In this case, the NPs serve to reduce both the monomeric
      friction and the entanglements in the polymer melt, as in the case of a polymer
      solvent system. However, for NPs larger than half the entanglement mesh size, the
      effective monomer relaxation is essentially unaffected for low NP concentrations.
      Even in this case, we observe a strong reduction in chain entanglements for
      larger NP loadings. Thus, the role of NPs is to always reduce the number of
      entanglements, with this effect only becoming pronounced for small NPs or for
      high concentrations of large NPs. Our studies of the relaxation of single chains
      resonate with recent neutron spin echo (NSE) experiments, which deduce a similar
      entanglement dilution effect. 

PMID- 25939278
TI  - Big Data in Vaccinology: Introduction and section summaries.

PMID- 25939277
TI  - Adolescent alcohol use before and after the high school transition.
AB  - BACKGROUND: An important question is whether the high school (HS) entry is a
      critical developmental event associated with escalation of alcohol use. This
      study examined trajectories of adolescent alcohol use as a function of a
      normative developmental event-the HS entry. In addition, given that at-risk youth
      may be particularly vulnerable to the stress associated with this transition, we
      examined how these alcohol use trajectories may be shaped by a measure of early
      behavioral risk, early adolescent delinquency. METHODS: Participants included 891
      twelve-year-olds from the prospective National Longitudinal Survey of Youth 1997
      for whom relevant longitudinal school data were available (51.2% boys; 61.4%
      White). RESULTS: Alcohol use after HS entry increased at a significantly greater
      rate than did use during the middle school years, even after accounting for
      students' age at transition. In addition, early delinquency emerged as a risk
      factor such that differences in alcohol use existed prior to the transition. That
      is, children with early delinquency characteristics displayed more rapid
      progression in alcohol use, but this effect was evident only during middle
      school. CONCLUSIONS: HS entry appears to be a critical developmental event
      associated with increased social risk for greater alcohol use that goes beyond
      the simple maturational (i.e., aging) factors. Youth with behavioral problems
      appears to be at greater risk in middle school, in contrast to lower risk youth
      for whom HS entry may be a more critical event, in part because HS may be a less
      restrictive environment and/or because alcohol use becomes more normative at that
      time. Adolescent substance use may be described as a series of distinct
      developmental stages that closely correspond to school transitions and suggest a
      critical period for targeted intervention that may differ as a function of
      preexisting risk.

PMID- 25939279
TI  - Development of EV71 virus-like particle purification processes.
AB  - Enterovirus 71 (EV71) causes the outbreaks of hand-foot-and-mouth disease and
      results in deaths of hundreds of young children. EV71 virus-like particles (VLPs)
      are empty capsids consisting of viral structural proteins and can elicit potent
      immune responses, thus holding promise as an EV71 vaccine candidate. However, an
      efficient, scalable production and purification scheme is missing. For mass
      production of EV71 VLPs, this study aimed to develop a production and
      chromatography-based purification process. We first demonstrated the successful
      EV71 VLPs production in the stirred-tank bioreactor in which High FiveTM cells
      were infected with a recombinant baculovirus co-expressing EV71 structural
      polyprotein P1 and protease 3CD. The culture supernatant containing the VLPs was
      subjected to tangential flow filtration (TFF) for concentration/diafiltration,
      which enabled the removal of >80% of proteins while recovering >80% of VLPs. The
      concentrated VLPs were next subjected to hydroxyapatite chromatography (HAC) in
      which the VLPs were mainly found in the flow through. After another TFF
      concentration/diafiltration, the VLPs were purified by size-exclusion
      chromatography (SEC) and concentrated/diafiltered by a final TFF. The integrated
      process yielded an overall VLPs recovery of ~ 36% and a purity of ~ 83%, which
      was better or comparable to the recovery and purity for the purification of live
      EV71 virus particles. This process thus may move the EV71 VLPs vaccine one step
      closer to the clinical applications.

PMID- 25939280
TI  - Unusual positive effects from vaccines need to be reported - They represent a
      resource that could lead to new treatment strategies.

PMID- 25939281
TI  - The human T-cell repertoire grows up.

PMID- 25939282
TI  - The structure and function of presynaptic endosomes.
AB  - The function of endosomes and of endosome-like structures in the presynaptic
      compartment is still controversial. This is in part due to the absence of a
      consensus on definitions and markers for these compartments. Synaptic endosomes
      are sometimes seen as stable organelles, permanently present in the synapse.
      Alternatively, they are seen as short-lived intermediates in synaptic vesicle
      recycling, arising from the endocytosis of large vesicles from the plasma
      membrane, or from homotypic fusion of small vesicles. In addition, the potential
      function of the endosome is largely unknown in the synapse. Some groups have
      proposed that the endosome is involved in the sorting of synaptic vesicle
      proteins, albeit others have produced data that deny this possibility. In this
      review, we present the existing evidence for synaptic endosomes, we discuss their
      potential functions, and we highlight frequent technical pitfalls in the analysis
      of this elusive compartment. We also sketch a roadmap to definitely determine the
      role of synaptic endosomes for the synaptic vesicle cycle. Finally, we propose a
      common definition of synaptic endosome-like structures. 

PMID- 25939283
TI  - Evidence that 3-hydroxy-3-methylglutaric and 3-methylglutaric acids induce DNA
      damage in rat striatum.
AB  - 3-Hydroxy-3-methylglutaryl-CoA lyase (HL) deficiency is a rare autosomal
      recessive disorderaffecting the final step of leucine degradation and ketogenesis
      and biochemically characterized by the predominant accumulation of 3-hydroxy-3
      methylglutaric (HMG) and 3-methylglutaric (MGA) acids in biological fluids and
      tissues of affected patients. Considering that previous studies reported that HMG
      and MGA have pro oxidant properties, the present study evaluated the ex vivo and
      in vitro effects of HMG and MGA on frequency and index of DNA damage in cerebral
      cortex and striatum of young rats. The ex vivo effects of both organic acids on 8
      hydroxy-2'-deoxyguanosine (OHdG) levels and their in vitro effects on 2',7'
      dichlorofluorescin (DCFH) oxidation and glutathione (GSH) concentrations in rat
      striatum were also determined. We also investigated the ex vivo effects of both
      organic acids on 8-hydroxy-2'-deoxyguanosine (OHdG) levels in rat striatum. In
      the ex vivo experiments, DNA damage was determined in striatum homogenates
      prepared 30 min after a single intrastriatal administration of HMG or MGA. On the
      other hand, the in vitro evaluation was performed after an incubation of rat
      cerebral cortex or striatum homogenates or slices in the presence of HMG or MGA
      during 1 h at 37  degrees C. We observed that the intrastriatal administration of
      HMG and MGA increased the frequency and the index of DNA damage, as well as OHdG
      staining in rat striatum. We also verified that MGA, but not HMG, increased DNA
      damage frequency and index in vitro in striatum of rats. In contrast, no
      alterations were verified in vitro in cerebral cortex. Finally, we found that HMG
      and MGA increased DCFH oxidation and decreased GSH concentrations in rat
      striatum. Therefore, it may be presumed that DNA damage provoked by HMG and MGA
      possibly via reactive species generation is involved, at least in part, in the
      pathophysiology of brain injury, particularly in the striatum of HL-deficient
      patients. 

PMID- 25939284
TI  - Mental incapacity and criminal liability: Redrawing the fault lines?
AB  - The proper boundaries of criminal liability with respect to those with
      questionable mental capacity are currently under review. In its deliberations in
      the areas of unfitness to plead, automatism and the special verdict of not guilty
      by reason of insanity the Law Commission for England and Wales have been
      cognizant of particular difficulties in fairly attributing criminal
      responsibility to those whose mental capacities may or may not have impinged on
      their decisions, either at the time of the offence or at trial. And they have
      referenced the potential breaches of the European Convention on Human Rights
      (ECHR) posed by the state of our current laws. However, in their efforts to
      remedy these potential deficiencies is the Law Commission heading in a direction
      that is fundamentally incompatible with the direction embodied by the United
      Nations Convention on the Rights of People with Disabilities (CRPD)? Whether one
      must cede sensibly to the other, or whether some compromise might emerge, perhaps
      through an extension of supportive services or through the development of
      disability-neutral criminal law, forms the subject of this paper. 

PMID- 25939285
TI  - Who needs capacity?
AB  - The UK Law Commission's Discussion Paper, Criminal Liability: Insanity and
      Automatism, recommends introducing the concept of capacity to the insanity
      defence. The concept of capacity has an established role in those parts of the
      law that concern the validity of the decisions that people make, for instance in
      composing a will or entering into a contract. Making mental capacity a criterion
      for criminal responsibility in a mentally disordered defendant, however, is
      potentially problematic. First, the term capacity already has several different
      meanings in the literature on the jurisprudence of mental abnormality. Second,
      using the concept of capacity in the way that the Law Commission proposes poses
      difficulties that relate to the provision of testimony by expert witnesses. 

PMID- 25939286
TI  - Fluctuating capacity and advance decision-making in Bipolar Affective Disorder -
      Self-binding directives and self-determination.
AB  - For people with Bipolar Affective Disorder, a self-binding (advance) directive
      (SBD), by which they commit themselves to treatment during future episodes of
      mania, even if unwilling, can seem the most rational way to deal with an
      imperfect predicament. Knowing that mania will almost certainly cause enormous
      damage to themselves, their preferred solution may well be to allow trusted
      others to enforce treatment and constraint, traumatic though this may be. No
      adequate provision exists for drafting a truly effective SBD and efforts to
      establish such provision are hampered by very valid, but also paralysing ethical,
      clinical and legal concerns. Effectively, the autonomy and rights of people with
      bipolar are being 'protected' through being denied an opportunity to protect
      themselves. From a standpoint firmly rooted in the clinical context and
      experience of mania, this article argues that an SBD, based on a patient-centred
      evaluation of capacity to make treatment decisions (DMC-T) and grounded within
      the clinician-patient relationship, could represent a legitimate and ethically
      coherent form of self-determination. After setting out background information on
      fluctuating capacity, mania and advance directives, this article proposes a
      framework for constructing such an SBD, and considers common objections, possible
      solutions and suggestions for future research. 

PMID- 25939287
TI  - Antifungal stewardship: towards defining safe stopping criteria for therapeutic
      oral azoles.

PMID- 25939288
TI  - Protective effects of polyphenol-rich blackcurrant preparation on biochemical and
      metabolic biomarkers of rats fed a diet high in fructose.
AB  - The purpose of the study was to compare in vivo effects of dietary
      supplementation with blackcurrant pomaces containing variable level of phenolic
      compounds on blood and internal organ parameters in rats. Forty-eight growing
      Wistar rats were allocated to six treatment groups in which they were fed ad
      libitum for 4 weeks the following diets: standard chow (group S), high-fructose
      diet (group F), standard chow supplemented with 7.7% of either rich in
      polyphenols unprocessed blackcurrant pomace (UB) or polyphenol-deprived processed
      pomace (PB) (groups SUB and SPB respectively), and high-fructose diet with 7.7%
      of either UB or PB (groups FUB and FPB respectively). Blackcurrant pomace,
      irrespective of its phenolic content, selectively modulated the enzymatic
      activity of the colon microflora, reducing the activity of enzymes with
      potentially harmful properties and promoting activities of enzymes that might
      increase the use of carbohydrates that escaped digestion in the upper
      gastrointestinal tract. Although both pomaces increased antioxidant status of the
      liver and blood serum, the unprocessed pomace showed a greater ability to inhibit
      lipid peroxidation in heart and kidney than the pomace that was less abundant in
      polyphenols. Both of the examined pomaces had a positive influence on serum lipid
      profile, but better hypocholesterolemic effect was observed after supplementation
      of the diet with unprocessed preparation. The biochemical action of unprocessed
      pomace in the normalization of fructose-induced disturbances was more distinct
      than those of pomace remaining after extraction.

PMID- 25939289
TI  - D2-40 negative pyogenic granuloma-like Kaposi's sarcoma: Diagnostic features and
      histogenetic hypothesis of an uncommon skin tumor in HIV-negative patients.
AB  - Pyogenic granuloma-like Kaposi's sarcoma (PGLKS) is a recently described skin
      tumor showing features both of pyogenic granuloma (PG) and Kaposi's sarcoma (KS).
      The differential diagnosis is often challenging. We reviewed a series of 50 PG
      and 23 Ks located on distal extremities with the aid of an immunohistochemical
      panel comprising CD34, CD31, FVIII, SMA, D2-40, HHV8. After revision, 6/50 PG
      lesions previously diagnosed as PG, showed positive immunostaining for LNA1-HHV8
      and focal positivity for CD31 and FVIII in the endothelial cells of the
      proliferating vessels, with some SMA positive pericytes. D2-40, a marker of
      lymphatic endothelium positive in KS, stained negatively. These lesions were
      renamed PGLKS. Of note, in our series, PGLKS represented the only form of KS
      localized in the hand; all the patients were HIV-negative, older than PG
      patients, with a prevalence for male gender. PGLKS and PG need a different
      management and a follow-up is advisable for PGLKS, as for the other variants of
      KS. To date, D2-40 negative immunostaining has not yet been reported in PGLKS and
      should not lead to a misdiagnosis of PG. The morphological similarities with PG
      and the immunohistochemical findings, showing a defective phenotype of the
      neoplastic cells, suggest a histogenetic hypothesis in which D2-40 negative PGLKS
      could represent an early stage of HHV8 infection of a pre-existing PG, whose
      vessels loose progressively their blood vascular markers but have not still
      acquired the lymphatic ones. 

PMID- 25939290
TI  - Psychometric assessment of the Japanese version of the Revised Fibromyalgia
      Impact Questionnaire: reliability and validity.
AB  - AIM: To assess the psychometric properties of the Japanese version of the Revised
      Fibromyalgia Impact Questionnaire (JFIQR) in fibromyalgia (FM) patients. METHOD:
      The reliability and validity of the JFIQR were assessed using online data
      collected from Japanese FM patients. Reliability was evaluated based on test
      retest reliability results and internal consistency; validity was evaluated on
      the basis of concurrent and known-group validity. RESULTS: A total of 105
      patients completed the online questionnaire. Intra-class correlation coefficients
      for test-retest were 0.91 for the JFIQR total score with a range of 0.84-0.90 in
      three domains: function, overall impact and symptoms. Internal consistency
      results indicated a Cronbach's alpha of 0.90 for the total score with a range of
      0.83 and 0.85 for the domains. Concurrent validity results showed that the total
      score was correlated to all external criteria (Japanese version of the
      Fibromyalgia Impact Questionnaire, Fibromyalgia Activity Scale-31, Medical
      Outcomes Study 36-item Short-Form health survey) from a moderate to strong degree
      with most indicating a strong correlation. Results of known-group validity showed
      that the JFIQR total score is capable of discriminating between FM and the other
      groups, such as rheumatic arthritis and no chronic pain (P < 0.0001 for all
      pairwise comparisons). CONCLUSION: The current psychometric assessment of the
      JFIQR demonstrated that it is a reliable and valid questionnaire in Japanese
      patients with FM. Usefulness of the JFIQR in clinical studies and medical
      practice for Japanese-speaking populations is expected.

PMID- 25939291
TI  - Familial hypercholesterolemia.
AB  - Familial hypercholesterolemia is a common, inherited disorder of cholesterol
      metabolism that leads to early cardiovascular morbidity and mortality. It is
      underdiagnosed and undertreated. Statins, ezetimibe, bile acid sequestrants,
      niacin, lomitapide, mipomersen, and low-density lipoprotein (LDL) apheresis are
      treatments that can lower LDL cholesterol levels. Early treatment can lead to
      substantial reduction of cardiovascular events and death in patients with
      familial hypercholesterolemia. It is important to increase awareness of this
      disorder in physicians and patients to reduce the burden of this disorder.

PMID- 25939292
TI  - New cholesterol guidelines for the management of atherosclerotic cardiovascular
      disease risk: a comparison of the 2013 American College of Cardiology/American
      Heart Association cholesterol guidelines with the 2014 National Lipid Association
      recommendations for patient-centered management of dyslipidemia.
AB  - This review discusses the 2013 American College of Cardiology (ACC)/American
      Heart Association (AHA) Guideline on the Treatment of Blood Cholesterol to Reduce
      Atherosclerotic Cardiovascular Risk in Adults and compares it with the 2014
      National Lipid Association (NLA) Recommendations for Patient-Centered Management
      of Dyslipidemia. The review discusses some of the distinctions between the
      guidelines, including how to determine a patient's atherosclerotic cardiovascular
      disease risk, the role of lipoprotein treatment targets, the importance of
      moderate- and high-intensity statin therapy, and the use of nonstatin therapy in
      light of the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial
      (IMPROVE-IT) trial.

PMID- 25939293
TI  - Lipoprotein apheresis.
AB  - Patients with familial hypercholesterolemia (FH) have early development of
      atherosclerosis and cardiovascular disease (CVD). Lipid level-lowering
      medications are not always successful in reducing increased low-density
      lipoprotein C (LDL-C) levels. Lipoprotein apheresis (LA) therapy has proven its
      clinical benefit in reducing CVD events for patients with FH with
      hypercholesterolemia. LA reduces LDL-C levels by more than 60% in patients with
      FH and reduces CVD events. LA also reduces Lp(a) levels and CVD events. LA
      reduces inflammatory markers and blood viscosity. 

PMID- 25939294
TI  - Dyslipidemia in pregnancy.
AB  - "Recent studies have revealed evidence that poorly controlled cholesterol,
      triglycerides, and their metabolites during pregnancy may be associated with
      cardiometabolic dysfunction and have significant detrimental fetal and maternal
      vascular consequences. Cardiometabolic dysfunction during pregnancy may not only
      contribute to long-term effects of the mother and child's vascular health but
      also potentially create cardiovascular risk for generational offspring. This
      article provides updates on this rapidly expanding and multifaceted topic and
      reviews new insight regarding why recognition of this disordered maternal
      cholesterol and triglyceride metabolism is likely to have long-term effect on the
      increasing atherosclerotic burden of the burgeoning population."

PMID- 25939295
TI  - Women's Health Considerations for Lipid Management.
AB  - Understanding opportunities to reduce dyslipidemia before, during, and after
      pregnancy has major implications for cardiovascular disease risk prevention for
      the entire population. The best time to screen for dyslipidemia is before
      pregnancy or in the early antenatal period. The differential diagnosis of
      hypertriglyceridemia in pregnancy is the same as in nonpregnant women except that
      clinical lipidologists need to be aware of the potential obstetric complications
      associated with hypertriglyceridemia. Dyslipidemia discovered during pregnancy
      should be treated with diet and exercise intervention, as well as glycemic
      control if indicated. A complete lipid profile assessment during each trimester
      of pregnancy is recommended.

PMID- 25939296
TI  - Statins and diabetes.
AB  - A statin is first-line drug therapy for dyslipidemia. Clinical trial data suggest
      there is an increase in the incidence of new-onset type 2 diabetes mellitus with
      statin use. The National Lipid Association (NLA) Statin Diabetes Safety Task
      Force concluded that the cardiovascular benefit of statin therapy outweighs the
      risk for developing diabetes. The NLA panel advocated following the standards of
      care from the American Diabetes Association for screening and diagnosis of
      diabetes, and emphasized the importance of lifestyle modification. This article
      summarizes NLA's review of the evidence, expanding it to include recent results,
      and outlines the clinical recommendations.

PMID- 25939297
TI  - Statins and cognitive side effects: what cardiologists need to know.
AB  - Statins are widely used in secondary and primary prevention of atherosclerotic
      cardiovascular disease. They reduce cardiovascular events and mortality, and have
      an excellent safety record. Recent case reports suggest a possible association
      between statins and adverse effects on cognition. This article reviews recent
      literature related to statins and cognition and provides recommendations to
      clinicians. Cognitive considerations should not play a role in decision making
      for most patients for whom statins are indicated. Future trials of statin, or any
      novel antilipemic agent should include systematic assessment of cognition.

PMID- 25939298
TI  - Statins and the liver.
AB  - Lipid lowering, particularly with 3-hydroxy-3-methylglutaryl-coenzyme A reductase
      inhibitors ("statins"), reduces the risk of cardiovascular disease. Patients with
      chronic liver disease present challenges to the use of lipid medications. In the
      case of most liver disorders, the concern has been one of safety. There is
      evidence that most lipid-lowering medications can be used safely in many
      situations, although large outcomes trials are lacking. This review examines
      lipid physiology and cardiovascular risk in specific liver diseases and reviews
      the evidence for lipid lowering and the use of statins in chronic liver disease.

PMID- 25939299
TI  - Genetic testing in hyperlipidemia.
AB  - Hereditary dyslipidemias are often underdiagnosed and undertreated, yet with
      significant health implications, most importantly causing preventable premature
      cardiovascular diseases. The commonly used clinical criteria to diagnose
      hereditary lipid disorders are specific but are not very sensitive. Genetic
      testing may be of value in making accurate diagnosis and improving cascade
      screening of family members, and potentially, in risk assessment and choice of
      therapy. This review focuses on using genetic testing in the clinical setting for
      lipid disorders, particularly familial hypercholesterolemia.

PMID- 25939300
TI  - Lipid management in human immunodeficiency virus.
AB  - The development and use of antiretroviral medications to treat patients infected
      with human immunodeficiency virus (HIV) has dramatically changed the course of
      this disease from one that was fatal to a chronic and more manageable condition.
      Recommendations and guidelines for the general population are presented in this
      review with suggestions as to how they may be applied to this patient population.
      Issues for which there is little or no information available are noted to
      highlight the many gaps in our knowledge regarding diagnosis and management of
      dyslipidemia for patients living with HIV.

PMID- 25939301
TI  - Managing residual risk after myocardial infarction among individuals with low
      cholesterol levels.
AB  - About one-half of individuals with an acute myocardial infarction have a low
      density lipoprotein cholesterol level of less than 100 mg/dL at the time of
      occurrence, but remain at risk for recurrent events. This residual risk is likely
      mediated by multiple factors, including burden of atherosclerosis, residual
      dyslipidemia, nonlipid risk factors, and suboptimal implementation of lifestyle
      therapy and evidence-based pharmacologic therapy. This article reviews management
      options for this high-risk population.

PMID- 25939302
TI  - Management of hypertriglyceridemia for prevention of atherosclerotic
      cardiovascular disease.
AB  - Mendelian randomization data strongly suggest that hypertriglyceridemia (HTG)
      causes atherosclerotic cardiovascular disease (ASCVD), and so triglyceride (TG)
      level-lowering treatment in HTG is now more strongly recommended to address the
      residual ASCVD risk than has been the case in (generally earlier) published
      guidelines. Fibrates are the best-established agents for TG level lowering and
      are generally used as first-line treatment of TG levels greater than 500 mg/dL.
      Statins are the best-established agents for ASCVD prevention, and so are usually
      used as first-line treatment of TG levels less than 500 mg/dL.

PMID- 25939303
TI  - Dyslipidemia in special ethnic populations.
AB  - This article reviews racial/ethnic differences in dyslipidemia-prevalence of
      dyslipidemia, its relation to coronary heart disease (CHD) and stroke mortality
      rates, response to lipid-lowering agents, and lifestyle modification. Asian
      Indians, Filipinos, and Hispanics are at higher risk for dyslipidemia, which is
      consistent with the higher CHD mortality rates in these groups. Statins may have
      greater efficacy for Asians, but the data are mixed. Lifestyle modifications are
      recommended. Culturally-tailored prevention and intervention should be provided
      to the minority populations with elevated risk for dyslipidemia and considerably
      more research is needed to determine the best approaches to helping specific
      subgroups.

PMID- 25939304
TI  - The world and lipidology as it relates to cardiology.

PMID- 25939305
TI  - Parental satisfaction with inpatient care of children with cerebral palsy.
AB  - AIM: Children with cerebral palsy (CP) have complex health-care needs. This study
      examines levels of parental satisfaction with inpatient care for children with CP
      at a tertiary care hospital to identify areas for improvement. METHODS:
      Parents/guardians of children with CP and parents/guardians of children without a
      disability admitted to hospital completed a custom-designed questionnaire
      assessing six areas of the hospital admission: (i) the admission process; (ii)
      the child's personal care; (iii) the child's medical care; (iv) overall care of
      the child; (v) the parent's experience in hospital; and (vi) keeping up to date
      in hospital. Differences between the two groups were analysed using Student's t
      tests. RESULTS: Parents of children with CP were significantly less satisfied
      with the inpatient care as compared with parents of children without a disability
      in four of the six categories: 'my child's personal care' (P = 0.0033), 'my
      child's medical care' (P = 0.0350), 'overall care' (P = 0.0081) and 'my
      experience in the hospital' (P = 0.0209). When the overall questionnaire was
      compared between the two groups, parents of children with CP were less satisfied
      with care than parents of children without a disability (P = 0.0036). CONCLUSION:
      Parents of children with CP are less satisfied with the inpatient care of their
      child compared with parents of children without a disability. This information
      should be instrumental in informing change to ensure that parent satisfaction
      levels improve to a level consistent with other children admitted to a tertiary
      care setting.

PMID- 25939306
TI  - Post-poliomyelitis syndrome as a possible viral disease.
AB  - This review summarizes current concepts on post-polio syndrome (PPS), a condition
      that may arise in polio survivors after partial or complete functional recovery
      followed by a prolonged interval of stable neurological function. PPS affects 15
      20 million people worldwide. Epidemiological data are reported, together with the
      pathogenic pathways that possibly lead to the progressive degeneration and loss
      of neuromuscular motor units. As a consequence of PPS, polio survivors experience
      new weakness, generalized fatigue, atrophy of previously unaffected muscles, and
      a physical decline that may culminate in the loss of independent life. Emphasis
      is given to the possible pathogenic role of persistent poliovirus infection and
      chronic inflammation. These factors could contribute to the neurological and
      physical decline in polio survivors. A perspective is then given on novel anti
      poliovirus compounds and monoclonal antibodies that have been developed to
      contribute to the final phases of polio eradication. These agents could also be
      useful for the treatment or prevention of PPS. Some of these compounds/antibodies
      are in early clinical development. Finally, current clinical trials for PPS are
      reported. In this area, the intravenous infusion of normal human immunoglobulins
      appears both feasible and promising. 

PMID- 25939307
TI  - Angiotensin-converting enzyme inhibition prevents myocardial infarction-induced
      increase in renal cortical cGMP and cAMP phosphodiesterase activities.
AB  - We investigated whether myocardial infarction (MI) enhances renal
      phosphodiesterases (PDE) activities, investigating particularly the relative
      contribution of PDE1-5 isozymes in total PDE activity involved in both cGMP and
      cAMP pathways, and whether angiotensin-converting enzyme inhibition (ACEi)
      decreases such renal PDE hyperactivities. We also investigated whether ACEi might
      thereby improve atrial natriuretic peptide (ANP) efficiency. We studied renal
      cortical PDE1-5 isozyme activities in sham (SH)-operated, MI rats and in MI rats
      treated with perindopril (ACEi) 1 month after coronary artery ligation.
      Circulating atrial natriuretic peptide (ANP), its second intracellular messenger
      cyclic guanosine monophosphate (cGMP) and cGMP/ANP ratio were also determined.
      Cortical cGMP-PDE2 (80.3 vs. 65.1 pmol/min/mg) and cGMP-PDE1 (50.7 vs. 30.1
      pmol/min/mg), and cAMP-PDE2 (161 vs. 104.1 pmol/min/mg) and cAMP-PDE4 (307.5 vs.
      197.2 pmol/min/mg) activities were higher in MI than in SH rats. Despite
      increased ANP plasma level, ANP efficiency tended to be decreased in MI compared
      to SH rats. Perindopril restored PDE activities and tended to improve ANP
      efficiency in MI rats. One month after coronary ligation, perindopril treatment
      of MI rats prevents the increase in renal cortical PDE activities. This may
      contribute to increase renal ANP efficiency in MI rats. 

PMID- 25939308
TI  - Construction of unique six-coordinated titanium species with an organic amine
      ligand in titanosilicate and their unprecedented high efficiency for alkene
      epoxidation.
AB  - A novel organic-inorganic layered titanosilicate consisting of Ti-containing MWW
      type nanosheets and piperidine ligands was constructed. It exhibited an
      unprecedented high catalytic activity and recyclability in alkene epoxidation. 

PMID- 25939310
TI  - Risk factors for the development of osteoporosis after spinal cord injury. A 12
      month follow-up study.
AB  - Spinal cord injury (SCI) has been associated with a marked bone loss after injury
      and a consequent increased risk of osteoporosis. The evaluation of bone mineral
      density shortly after SCI is a simple and effective method for predicting the
      development of osteoporosis during the first year after SCI. INTRODUCTION: Spinal
      cord injury (SCI) has been associated with a marked bone loss after injury and a
      consequent increased risk of osteoporosis and fractures. The aim of this study
      was to analyze the factors associated with osteoporosis development short-term
      after SCI. METHODS: We included patients with complete recent SCI (<6 months)
      evaluating bone turnover markers (P1NP, bone ALP, and sCTx), 25-OH-vitamin D
      (25OHD) levels, and lumbar and femoral BMD (Lunar, Prodigy) at baseline, 6 and 12
      months after SCI. The risk factors for osteoporosis analyzed included the
      following: age, gender, BMI, toxic habits, bone turnover markers, 25OHD levels,
      lumbar and femoral BMD, level, severity and type of SCI, and days-since-injury.
      Osteoporosis was defined according to WHO criteria. RESULTS: Thirty-five patients
      aged 35 +/- 16 years were included, and 52 % developed osteoporosis during the 12
      month follow-up. These latter patients had lower BMD values at femur and lumbar
      spine and higher bone turnover markers at baseline. On multivariate analysis, the
      principal factors related to osteoporosis development were as follows: total
      femur BMD <1 g/cm(2) (RR, 3.61; 95 % CI 1.30-10.06, p = 0.002) and lumbar BMD
      <1.2 g/cm(2) at baseline (0.97 probability of osteoporosis with both parameters
      under these values). Increased risk for osteoporosis was also associated with
      increased baseline values of bone ALP (>14 ng/mL) (RR 2.40; 95 % CI 1.10-5.23, p
      = 0.041) and P1NP (>140 ng/mL) (RR 3.08; 95 % CI 1.10-8.57, p = 0.017).
      CONCLUSIONS: The evaluation of BMD at the lumbar spine and femur short-term after
      SCI is a simple, effective method for predicting the development of osteoporosis
      during the first year after SCI. Our results also indicate the need to evaluate
      and treat these patients shortly after injury.

PMID- 25939311
TI  - Osteoradionecrosis of the mandible: A ten year single-center retrospective study.
AB  - BACKGROUND: Numerous factors have been associated with the development of
      osteoradionecrosis (ORN) of the jaws. The purpose of this study was to
      investigate the factors that are linked to the severity of mandibular ORN.
      METHODS: A retrospective study was conducted which included all ORN cases treated
      in the Department of Oral and Maxillofacial Surgery in Munich (LMU) between 2003
      and 2012. The cases were categorized according to the necrosis stage and several
      variables were evaluated in order to identify possible correlation between them
      and the severity of the necrosis. RESULTS: A total of 115 patients with 153
      osteonecrosis lesions were included in the study. Twenty-three cases were of
      stage I, 31 were of stage II and 99 were of stage III. The initial tumors were
      predominantly located in the floor of the mouth, the tongue or the pharynx.
      Diabetes mellitus (OR: 4.955, 95% Cl: 1.965-12.495), active smoking (OR: 13.542,
      95% Cl: 2.085-87.947), excessive alcohol consumption (OR: 5.428, 95% Cl: 1.622
      18.171) and dental treatment and/or local pathological conditions (OR: 0.237, 95%
      Cl: 0.086-0.655) were significant predictors for stage III necrosis. CONCLUSIONS:
      The aforementioned factors are predictive of ORN severity and can guide its
      prophylaxis and management.

PMID- 25939312
TI  - Health-related quality of life after segmental resection of the lateral mandible:
      Free fibula flap versus plate reconstruction.
AB  - OBJECTIVES: Segmental resection of the mandible causes functional, aesthetic and
      social problems affecting health-related quality of life (HRQoL). It is often
      assumed that reconstruction with composite free flaps guarantees better function
      and aesthetics than bridging the defect with reconstruction plates. METHODS:
      Using the European Organization for Research and Treatment of Cancer
      questionnaires (EORTC QLQ-C30 version 3.0 and EORTC QLQ-H&N35), we compared HRQoL
      in patients who received free fibula flaps versus reconstruction plates after
      segmental resection of the lateral mandible. RESULTS: Thirty-seven completed
      questionnaires (18 fibula reconstructions and 19 patients with reconstruction
      plates) were available. Reconstruction with a free fibula flap did not provide
      clear additional benefit to bridging the defect with a reconstruction plate after
      segmental resection of the lateral mandible. In particular aspects known to have
      the most impact on HRQoL like swallowing, speech and chewing were not influenced
      by the type of reconstruction. CONCLUSIONS: Reconstruction of segmental defects
      of the lateral mandible with free fibula flap and reconstruction plate resulted
      in comparable HRQoL. If dental rehabilitation by means of dental implants is not
      anticipated in the fibula, then plate reconstruction with adequate soft tissue
      remains a suitable technique for the reconstruction of segmental defects of the
      lateral mandible.

PMID- 25939309
TI  - Presentation and management of osteoporosis presenting in association with
      pregnancy or lactation.
AB  - In this review, we summarize our current understanding of the pathophysiology of
      fragility fractures that occur for the first time during pregnancy and lactation,
      and provide guidance on appropriate investigations and treatment strategies. Most
      affected women will have had no prior bone density reading, and so the extent of
      bone loss that may have occurred during pregnancy or lactation is uncertain.
      During pregnancy, intestinal calcium absorption doubles in order to meet the
      fetal demand for calcium, but if maternal intake of calcium is insufficient to
      meet the combined needs of the mother and baby, the maternal skeleton will
      undergo resorption during the third trimester. During lactation, several hormonal
      changes, independent of maternal calcium intake, program a 5-10 % loss of
      trabecular mineral content in order to provide calcium to milk. After weaning the
      baby, the maternal skeleton is normally restored to its prior mineral content and
      strength. This physiological bone resorption during reproduction does not
      normally cause fractures; instead, women who do fracture are more likely to have
      additional secondary causes of bone loss and fragility. Transient osteoporosis of
      the hip may affect one or both femoral heads during pregnancy but it involves
      localized edema and not skeletal resorption. Case reports have described the use
      of calcitonin, bisphosphonates, strontium ranelate, teriparatide, vertebroplasty,
      and kyphoplasty to treat post-partum vertebral fractures. However, the need for
      such treatments is uncertain given that a progressive increase in bone mass
      subsequently occurs in most women who present with a fracture during pregnancy or
      lactation. 

PMID- 25939313
TI  - Impact of the lower third molar presence and position on the fragility of
      mandibular angle and condyle: A Three-dimensional finite element study.
AB  - The aim of the present study was to investigate the influences of the presence
      and position of a lower third molar (M3) on the fragility of mandibular angle and
      condyle, using finite element analysis. From computed tomographic scans of a
      human mandible with normally erupted M3, two additional virtual models were
      generated: a mandibular model with partially impacted M3 and a model without M3.
      Two cases of impact were considered: a frontal and a lateral blow. The results
      are based on the chromatic analysis of the distributed von Mises and principal
      stresses, and calculation of their failure indices. In the frontal blow, the
      angle region showed the highest stress in the case with partially impacted M3,
      and the condylar region in the case without M3. Compressive stresses were
      dominant but caused no failure. Tensile stresses were recorded in the retromolar
      areas, but caused failure only in the case with partially impacted M3. In the
      lateral blow, the stress concentrated at the point of impact, in the ipsilateral
      and contralateral angle and condylar regions. The highest stresses were recorded
      in the case with partially impacted M3. Tensile stresses caused the failure on
      the ipsilateral side, whereas compressive stresses on the contralateral side. 

PMID- 25939314
TI  - Dengue virus requires the CC-chemokine receptor CCR5 for replication and
      infection development.
AB  - Dengue is a mosquito-borne disease that affects millions of people worldwide
      yearly. Currently, there is no vaccine or specific treatment available. Further
      investigation on dengue pathogenesis is required to better understand the disease
      and to identify potential therapeutic targets. The chemokine system has been
      implicated in dengue pathogenesis, although the specific role of chemokines and
      their receptors remains elusive. Here we describe the role of the CC-chemokine
      receptor CCR5 in Dengue virus (DENV-2) infection. In vitro experiments showed
      that CCR5 is a host factor required for DENV-2 replication in human and mouse
      macrophages. DENV-2 infection induces the expression of CCR5 ligands. Incubation
      with an antagonist prevents CCR5 activation and reduces DENV-2 positive-stranded
      (+) RNA inside macrophages. Using an immunocompetent mouse model of DENV-2
      infection we found that CCR5(-/-) mice were resistant to lethal infection,
      presenting at least 100-fold reduction of viral load in target organs and
      significant reduction in disease severity. This phenotype was reproduced in wild
      type mice treated with CCR5-blocking compounds. Therefore, CCR5 is a host factor
      required for DENV-2 replication and disease development. Targeting CCR5 might
      represent a therapeutic strategy for dengue fever. These data bring new insights
      on the association between viral infections and the chemokine receptor CCR5. 

PMID- 25939315
TI  - Hypergastrinemia is associated with adenocarcinomas in the gastric corpus and
      shorter patient survival.
AB  - Hypergastrinemia causes carcinoids or carcinomas in the gastric corpus in animal
      models. Helicobacter pylori (HP) infection in patients causes atrophy,
      hypergastrinemia and promotes gastric carcinogenesis. Many patients with gastric
      cancer have hypergastrinemia and it has therefore been hypothesized that
      hypergastrinemia promotes carcinogenesis. We have examined the associations
      between serum gastrin, the anatomical localization of gastric cancer,
      histological classification and patient survival. Patients with non-cardia
      gastric adenocarcinomas were included prospectively (n = 80). Tumour
      localization, histological classification according to Lauren and disease stage
      were recorded. Preoperative fasting serum gastrin was analysed by
      radioimmunoassay and HP serology by ELISA. Patient survival was determined after
      a median postoperative follow-up of 16.5 years. Hypergastrinemic patients had
      carcinomas located in the gastric corpus more often compared to normogastrinemic
      patients (81.8 vs 36.2%, p = 0.002). Patients with disease stage 2-4 and
      hypergastrinemia had shorter survival than normogastrinemic patients [5.0 (1.1
      8.9) vs 10.0 (6.4-13.6) months (p = 0.04)]. There was no significant difference
      in serum gastrin or survival between patients with intestinal and diffuse type
      carcinomas. Hypergastrinemia was associated with adenocarcinomas in the gastric
      corpus and shorter survival. The findings support the hypothesis that
      hypergastrinemia promotes carcinogenesis and affects biological behaviour.

PMID- 25939316
TI  - Diagnostic ability of macular ganglion cell asymmetry for glaucoma.
AB  - BACKGROUND: Using spectral-domain optical coherence tomography (OCT), this study
      aims to investigate the glaucoma diagnostic ability of macular ganglion cell
      asymmetry analysis. DESIGN: A cross-sectional study was conducted. This study was
      performed to investigate glaucoma diagnostic ability of macular ganglion cell
      asymmetry analysis in eyes with various degrees of glaucoma. PARTICIPANTS: We
      enrolled 181 healthy eyes and 265 glaucomatous eyes. METHODS: Glaucomatous eyes
      were subdivided into pre-perimetric, early, moderate and advanced-to-severe
      glaucoma based on visual field test results. For each eye, macular ganglion cell
      inner plexiform layer (GCIPL) thickness was measured using OCT. Average GCIPL
      thickness, GCIPL thicknesses in superior and inferior hemispheres, absolute
      difference in GCIPL thickness between superior and inferior hemispheres and GCIPL
      asymmetry index calculated as the absolute value of log10 (inferior hemisphere
      thickness/superior hemisphere thickness) were analysed. MAIN OUTCOME MEASURES:
      Areas under the receiver operating characteristics curves (AUCs) of GCIPL
      parameter were calculated and compared. RESULTS: All of the GCIPL parameters
      showed good glaucoma diagnostic ability (AUCs >= 0.817, P < 0.01). AUCs of
      average, superior and inferior GCIPL thickness increased as the severity of
      glaucoma increased. GCIPL thickness difference and asymmetry index showed the
      highest AUCs in early and moderate glaucoma and lower AUCs in pre-perimetric and
      advanced-to-severe glaucoma. GCIPL thickness difference and asymmetry index
      showed better glaucoma diagnostic ability than other GCIPL parameters only in
      early stage of glaucoma (P < 0.05); in other stages, these parameters had similar
      to or worse glaucoma diagnostic ability than other GCIPL parameters. CONCLUSIONS:
      Macular ganglion cell asymmetry analysis showed good glaucoma diagnostic ability,
      especially in early-stage glaucoma. However, it has limited usefulness in other
      stages of glaucoma.

PMID- 25939317
TI  - Structural change of NaO1/2-WO3-NbO5/2-LaO3/2-PO5/2 glass induced by
      electrochemical substitution of sodium ions with protons.
AB  - Structural changes of 35NaO1/2-1WO3-8NbO5/2-5LaO3/2-51PO5/2 glass (1W-glass)
      before and after the electrochemical substitution of sodium ions with protons by
      alkali-proton substitution (APS) are studied by Raman and (31)P magic-angle
      spinning nuclear magnetic resonance (MAS-NMR) spectroscopies. The glass before
      APS consists of (PO3(-))8.6(P2O7(4-)) chains on average and the terminal Q(1)
      units (-O-PO3(3-)) are bound to MO6 octahedra (M denotes niobium or tungsten)
      through P-O-M bonds. Some non-bridging oxygens (NBOs) in the MO6 octahedra are
      present in addition to the bridging oxygens (BOs) in P-O-M bonds. APS induces
      fragmentation of the phosphate chains because the average chain length decreases
      to (PO3(-))3.7(P2O7(4-)) after APS, despite the total number of modifier cations
      of sodium and lanthanum ions and protons being unaffected by APS. This
      fragmentation is induced by some of the NBOs in the MO6 octahedra before APS,
      changing to BOs of the newly formed M-O-P bonds after APS, because of the
      preferential formation of P-OH bonds over M-OH ones in the present glass. We show
      that APS under the conditions used here is not a simple substitution of sodium
      ions with protons, but it is accompanied by the structural relaxation of the
      glass to stabilize the injected protons. 

PMID- 25939320
TI  - Analysis for gender differences needed.

PMID- 25939318
TI  - Risks associated with the non-medicinal use of cannabis.
AB  - BACKGROUND: Cannabis is the most commonly consumed illicit drug around the world;
      in Germany, about 4.5% of all adults use it each year. Intense cannabis use is
      associated with health risks. Evidence-based treatments are available for health
      problems caused by cannabis use. METHODS: Selective literature review based on a
      search of the PubMed database, with special emphasis on systematic reviews, meta
      analyses, cohort studies, randomized controlled trials (RCTs), case-control
      studies, and treatment guidelines. RESULTS: The delta-9-tetrahydrocannabinol
      content of cannabis products is rising around the world as a result of plant
      breeding, while cannabidiol, in contrast, is often no longer detectable. Various
      medical conditions can arise acutely after cannabis use, depending on the user's
      age, dose, frequency, mode and situation of use, and individual disposition;
      these include panic attacks, psychotic symptoms, deficient attention, impaired
      concentration, motor incoordination, and nausea. In particular, intense use of
      high doses of cannabis over many years, and the initiation of cannabis use in
      adolescence, can be associated with substance dependence (DSM-5; ICD-10),
      specific withdrawal symptoms, cognitive impairment, affective disorders,
      psychosis, anxiety disorders, and physical disease outside the brain (mainly
      respiratory and cardiovascular conditions). At present, the most effective way to
      treat cannabis dependence involves a combination of motivational encouragement,
      cognitive behavioral therapy, and contingency management (level 1a evidence). For
      adolescents, family therapy is also recommended (level 1a evidence). No
      pharmacological treatments can be recommended to date, as evidence for their
      efficacy is lacking. CONCLUSION: Further research is needed to elucidate the
      causal relationships between intense cannabis use and potential damage to
      physical and mental health. Health problems due to cannabis use can be
      effectively treated.

PMID- 25939319
TI  - Somatoform disorders and medically unexplained symptoms in primary care.
AB  - BACKGROUND: The literature contains variable figures on the prevalence of
      somatoform disorders and medically unexplained symptoms in primary care. METHODS:
      The pertinent literature up to July 2014 was retrieved by a systematic search in
      the PubMed/MEDLINE, PsychInfo, Scopus, and Cochrane databases. The methodological
      quality and heterogeneity (I2) of the retrieved trials were analyzed. The
      prevalence rates of medically unexplained symptoms, somatoform disorders, and
      their subcategories were estimated, along with corresponding 95% confidence
      intervals (CI), with the aid of random-effects modeling. RESULTS: From a total of
      992 identified publications, 32 studies from 24 countries involving a total of 70
      085 patients (age range, 15-95 years) were selected for further analysis. All had
      been carried out between 1990 and 2012. The primary studies were more
      heterogeneous overall; point prevalences for the strict diagnosis of a
      somatization disorder ranged from 0.8% (95% CI 0.3-1.4%, I2 = 86%) to 5.9% (95%
      CI 2.4-9.4%, I2 = 96%), with higher estimated prevalences in studies that applied
      less restrictive diagnostic criteria. At least one type of somatoform disorder
      was diagnosable by DSM-IV and/or ICD-10 criteria in a fraction of primary-care
      patients that ranged from 26.2% (95% CI 19.1-33.3%, I2 = 98%) to 34.8% (95% CI
      26.6-44.6%; I2 = 92%). The percentage of patients complaining of at least one
      medically unexplained symptom ranged from 40.2% (95% CI 0.9-79.4%; I2 = 98%) to
      49% (95% CI 18-79.8%, I2 = 98%). The quality of the studies, in general, was only
      moderate. No relationship was found between study quality and prevalence
      estimates. CONCLUSION: The statistical heterogeneity of the included studies is
      very high. Somatoform disorders and medically unexplained symptoms are more
      common than generally assumed. The found prevalences highlight the importance of
      these conditions in primary care.

PMID- 25939321
TI  - In reply.

PMID- 25939322
TI  - Epigenetics in lung cancer diagnosis and therapy.
AB  - Lung cancer is the leading cause of cancer-related deaths worldwide. The
      initiation and progression of lung cancer is the result of the interaction
      between permanent genetic and dynamic epigenetic alterations. DNA methylation is
      the best studied epigenetic mark in human cancers. Altered DNA methylation in
      cancer was identified in 1983. Within 30 years of this discovery, DNA methylation
      inhibitors are used clinically to treat a variety of cancers, highlighting the
      importance of the epigenetic basis of cancer. In addition, histone modifications,
      nucleosome remodeling, and micro RNA (miRNA)-mediated gene regulation are also
      fundamental to tumor genesis. Distinct chromatin alterations occur in all stages
      of lung cancer, including initiation, growth, and metastasis. Therefore, stage
      specific epigenetic changes can be used as powerful and reliable tools for early
      diagnosis of lung cancer and to monitor patient prognosis. Moreover, since
      epigenetic changes are dynamic and reversible, chromatin modifiers are promising
      targets for the development of more effective therapeutic strategies against
      cancer. This review summarizes the chromatin alterations in lung cancer, focusing
      on the diagnostic and therapeutic approaches targeting epigenetic modifications
      that could help to reduce the high case-fatality rate of this dreadful disease.

PMID- 25939323
TI  - Cardiopulmonary resuscitation for in-hospital events in the emergency department:
      A comparison of adult and pediatric outcomes and care processes.
AB  - OBJECTIVES: To compare outcomes from in-hospital cardiopulmonary resuscitation
      (CPR) in the emergency department (ED) for pediatric and adult patients and to
      identify factors associated with differences in outcomes between children and
      adults. METHODS: Retrospective analysis of the Get With The Guidelines-
      Resuscitation database from January 1, 2000 to September 30, 2010. All patients
      with CPR initiated in the ED requiring chest compressions for >= 2 min were
      eligible; trauma patients were excluded. Patients were divided into children (<18
      yo) and adults (>= 18 yo). Patient, event, treatment, and hospital factors were
      analyzed for association with outcomes. Univariate analysis was performed
      comparing children and adults. Multivariate analysis was used to determine
      factors associated with outcomes. RESULTS: 16,834 events occurred in 608 centers
      (16,245 adult, 537 pediatric). Adults had more frequent return of spontaneous
      circulation (53% vs 47%, p = 0.02), 24h survival (35% vs 30%, p = 0.02), and
      survival to discharge (23% vs 20%, p = NS) than children. Children were less
      frequently monitored (62% vs 82%) or witnessed (79% vs 88%), had longer duration
      (24 m vs 17 m), more epinephrine doses (3 vs 2), and more frequent intubation
      attempts (64% vs 55%) than adults. There were no differences in time to
      compressions, vasopressor administration, or defibrillation between children and
      adults. On multivariate analysis, age had no association with outcomes.
      CONCLUSIONS: Survival following CPR in the ED is similar for adults and children.
      While univariate differences exist between children and adults, neither age nor
      specific processes of care are independently associated with outcomes.

PMID- 25939324
TI  - Initial end-tidal carbon dioxide as a prognostic indicator for inpatient PEA
      arrest.
AB  - AIM: Investigate the relationship of initial PetCO2 values of patients during
      inpatient pulseless electrical activity (PEA) cardiopulmonary arrest with return
      of spontaneous circulation (ROSC) and survival to discharge. METHODS: This study
      was performed in two urban, academic inpatient hospitals. Patients were enrolled
      from July 2009 to July 2013. A comprehensive database of all inpatient
      resuscitative events is maintained at these institutions, including demographic,
      clinical, and outcomes data. Arrests are stratified by primary etiology of arrest
      using a priori criteria. Inpatients with PEA arrest for whom recorded PetCO2 was
      available were included in the analysis. Capnography data obtained after ROSC
      and/or more than 10 min after initiation of CPR were excluded. Multivariable
      logistic regression was used to explore the association between initial PetCO2
      >20 mmHg and both ROSC and survival-to-discharge. RESULTS: A total of 50 patients
      with PEA arrest and pre-ROSC capnography were analyzed. CPR continued an average
      of 11.8 min after initial PetCO2 was recorded confirming absence of ROSC at time
      of measurement. Initial PetCO2 was higher in patients with versus without
      eventual ROSC (25.3 +/- 14.4 mmHg versus 13.4 +/- 6.9 mmHg, P = 0.003). After
      adjusting for age, gender, and arrest location (ICU versus non-ICU), initial
      PetCO2 >20 mmHg was associated with increased likelihood of ROSC (adjusted OR
      4.8, 95% CI 1.2-19.2, P = 0.028). Initial PetCO2 was not significantly associated
      with survival-to-discharge (P = 0.251). CONCLUSIONS: Initial PetCO2 >20 mmHg
      during CPR was associated with ROSC but not survival-to-discharge among inpatient
      PEA arrest victims. This analysis is limited by relatively small sample size.

PMID- 25939325
TI  - Protease Inhibitors Cause Necrotic Cell Death in Chlamydomonas reinhardtii by
      Inducing the Generation of Reactive Oxygen Species.
AB  - Protease inhibitors affecting the activity of the proteasome were reported to
      induce programmed cell death (apoptosis) in some mammalian cell lines. Proteasome
      activity can be suppressed by specific peptide derivatives and by N-tosyl-lysine
      chloromethyl-ketone (TLCK) and N-tosyl-phenylalanine-chloromethyl-ketone (TPCK),
      which affect the trypsine- and chymotrypsine-like activities of the proteasome,
      respectively. Particularly TLCK and TPCK caused necrotic cell death in the
      unicellular green alga Chlamydomonas reinhardtii. As a control, the effects of
      these protease inhibitors on the survival of human WISH cells were also studied.
      Bleaching of the Chlamydomonas cells after addition of TLCK or TPCK indicated
      that reactive oxygen species (ROS) were involved in this process. Indeed,
      increased levels of ROS were detected in Chlamydomonas cells treated with TLCK or
      TPCK. Furthermore, cell death induced by these protease inhibitors was
      accelerated by illumination and prevented or slowed down by scavengers of ROS. 

PMID- 25939326
TI  - You must remember this: How H2A.Z potentially links transcriptional memory to
      cognitive memory formation (comment on DOI 10.1002/bies.201400223).

PMID- 25939329
TI  - 3-D localization of non-radioactive strontium in osteoarthritic bone: Role in the
      dynamic labeling of bone pathological changes.
AB  - The study objective was to visualize regions of bone that undergo pathological
      mineralization and/or remodeling during pathogenesis of osteoarthritis, by
      employing non-radioactive strontium as a dynamic tracer of bone turnover. Post
      traumatic osteoarthritis was surgically induced in skeletally mature rats,
      followed by in vivo micro-CT imaging for 12 weeks to assess bone micro-structural
      changes. Rats either received strontium ranelate daily for the entire course of
      study or only last 10 days before euthanization. Distribution of strontium in
      bone was assessed in two and three dimensions, using electron probe micro
      analysis (EPMA) and synchrotron dual energy K-edge subtraction micro-CT (SRMUCT),
      respectively. Considerable early formation of osteophytes around the collateral
      ligament attachments and margins of articulating surfaces were observed, followed
      by subchondral sclerosis at the later stages. Accordingly, strontium was heavily
      incorporated by mineralizing osteophytes at 4, 8, and 12 weeks post-surgery,
      whereas subchondral bone only incorporated strontium between weeks 8-12.This
      study showed low dose stable strontium can effectively serve as a dynamic tracer
      of bone turnover to study pathological bone micro-structural changes, at
      resolution higher than nuclear medicine. Co-administration of strontium during
      therapeutic drug intervention may show enormous utility in assessing the efficacy
      of those compounds upon adaptive bone physiology.

PMID- 25939330
TI  - Combining Chemical Permeation Enhancers for Synergistic Effects.
AB  - Currently, macromolecular drugs such as proteins are mainly administered by means
      of injections due to their low intestinal epithelial permeability and poor
      stability in the gastrointestinal tract. This study investigated binary
      combinations of chemical drug absorption enhancers to determine if synergistic
      drug absorption enhancement effects exist. Aloe vera, Aloe ferox and Aloe
      marlothii leaf gel materials, as well as with N-trimethyl chitosan chloride
      (TMC), were combined in different ratios and their effects on the transepithelial
      electrical resistance (TEER), as well as the transport of FITC-dextran across
      Caco-2 cell monolayers, were measured. The isobole method was applied to
      determine the type of interaction that exists between the absorption enhancers
      combinations. The TEER results showed synergism existed for the combinations
      between A. vera and A. marlothii, A. marlothii and A. ferox as well as A. vera
      and TMC. Antagonism interactions also occurred and can probably be explained by
      chemical reactions between the chemical permeation enhancers, such as complex
      formation. In terms of FITC-dextran transport, synergism was found for
      combinations between A. vera and A. marlothii, A. marlothii and A. ferox, A. vera
      and TMC, A. ferox and TMC and A. marlothii and TMC, whereas antagonism was
      observed for A. vera and A. ferox. The combinations where synergism was obtained
      have the potential to be used as effective drug absorption enhancers at lower
      concentrations compared to the single components. 

PMID- 25939331
TI  - Concise and Practical Asymmetric Synthesis of a Challenging Atropisomeric HIV
      Integrase Inhibitor.
AB  - A practical and efficient synthesis of a complex chiral atropisomeric HIV
      integrase inhibitor has been accomplished. The combination of a copper-catalyzed
      acylation along with the implementation of the BI-DIME ligands for a ligand
      controlled Suzuki cross-coupling and an unprecedented
      bis(trifluoromethane)sulfonamide-catalyzed tert-butylation renders the synthesis
      of this complex molecule robust, safe, and economical. Furthermore, the overall
      synthesis was conducted in an asymmetric and diastereoselective fashion with
      respect to the imbedded atropisomer. 

PMID- 25939332
TI  - Single-Dose, Randomized, Open-Label, Two-Way, Crossover Bioequivalence Study of
      Two Formulations of Pregabalin 300 mg Hard Capsules in Healthy Volunteers Under
      Fasting Conditions.
AB  - AIMS: This bioequivalence study was conducted to assess the bioequivalence of two
      formulations, test and reference, of pregabalin 300 mg hard capsules, under
      fasting conditions. METHODS: This was a single-center, randomized, single-dose,
      open-label, laboratory-blinded, two-way crossover study, with a minimum washout
      period of 7 days. Plasma samples were collected prior to and up to 36 h after
      dosing. Pregabalin plasma concentrations were determined, using a validated
      method, by reversed phase high performance liquid chromatography coupled to a
      tandem mass spectrometry detector (LC-MS-MS). Pharmacokinetic metrics used for
      bioequivalence assessment were the AUC(0-t) (area under the plasma concentration
      time curve from time zero to time of last observed non-zero plasma concentration)
      and the C max (maximum observed plasma concentration). These parameters were
      determined from the pregabalin plasma concentration data using noncompartmental
      analysis. RESULTS: Forty healthy subjects, age ranging from 18 to 43 years old,
      were enrolled and randomized, of whom 39 completed the study. The ratio of
      geometric least square means for C max was 99.29 % (90 % confidence interval [CI]
      93.29-105.67). The ratio of geometric least square means for AUC(0-t) was 101.54
      % (90 % CI 100.13-102.98). The 90 % CIs were within the predefined range (80.00
      125.00). CONCLUSIONS: Bioequivalence between test and reference formulations,
      under fasting conditions, was concluded both in terms of rate and extent of
      absorption.

PMID- 25939333
TI  - Biocomparison of Three Formulations of the S1P1 Receptor Modulator Ponesimod in
      Healthy Subjects.
AB  - BACKGROUND: Ponesimod is a potent selective sphingosine-1-phosphate receptor 1
      (S1P1) modulator, which leads to a reduction in circulating lymphocytes,
      reflecting their sequestration within lymphoid organs. Modulation of the S1P1
      receptor has been previously described to be an effective treatment of autoimmune
      diseases (e.g., multiple sclerosis). OBJECTIVES: The aim of this study was to
      compare the relative bioavailability of two polymorphic forms of ponesimod in
      capsules (Form A versus Form C; Study 1) and the relative bioavailability of a
      capsule formulation and a tablet formulation (both polymorphic Form C; Study 2).
      METHODS: Two open-label, randomized, two-way crossover studies in healthy
      subjects were performed. In Study 1, 12 male subjects received a single dose of
      20 mg of polymorphic Form A or Form C of ponesimod in a capsule. In Study 2, 14
      male and female subjects (ratio 1:1) received a single dose of 40 mg of
      polymorphic Form C of ponesimod in either a capsule or a tablet formulation.
      Pharmacokinetic and safety variables (clinical laboratory test results, vital
      signs, and an electrocardiogram) were assessed. RESULTS: Comparison of the
      exposure to ponesimod following administration of the formulations in Study 1
      showed that the 90 % confidence intervals of the geometric mean ratios for the
      area under the curve from time zero to infinity (AUC0-inf), the area under the
      curve from time zero to the time of the last measurable concentration (AUC0-t),
      the terminal half-life (t 1/2), and the maximum plasma concentration (C max) were
      all within the 0.80-1.25 bioequivalence interval. In Study 2, more rapid
      absorption of ponesimod was observed from the tablet formulation than from the
      capsule formulation. There were no relevant differences in the safety and
      tolerability profiles between the different formulations. CONCLUSION: The two
      polymorphic forms of ponesimod and tablet versus capsule formulations were
      similar in terms of pharmacokinetics, safety, and tolerability.

PMID- 25939334
TI  - Greater Lateral Femorotibial Cartilage Loss in Osteoarthritis Initiative
      Participants With Incident Total Knee Arthroplasty: A Prospective Cohort Study.
AB  - OBJECTIVE: To explore whether baseline to 12-month followup change in
      femorotibial cartilage thickness differs between subjects who received a total
      knee arthroplasty (TKA) between 24 and 60 months from those without TKA (non
      TKA). METHODS: In this prospective cohort study, 531 right knees from
      Osteoarthritis Initiative participants with definite radiographic knee
      osteoarthritis (Kellgren/Lawrence [K/L] grades 2-4) were studied. Segmentation
      was applied to coronal fast low-angle shot magnetic resonance images, to
      quantitatively determine cartilage thickness in 16 femorotibial subregions.
      Unadjusted P values (t-tests) and P values adjusted for age, baseline body mass
      index (BMI), K/L grade, and sex (generalized estimating equation models) were
      used to evaluate differences in longitudinal 1-year rates of cartilage thickness
      between TKAs and non-TKAs, with total knee arthroplasty status as fixed effect.
      RESULTS: Of the 531 participants (mean +/- SD ages 63 +/- 9 years, BMI 30 +/- 4.8
      kg/m(2)), 40 received a femorotibial TKA within 4 years. At baseline, TKAs had
      thinner medial and lateral femorotibial cartilage (-15%; P < 0.001) than non
      TKAs. Longitudinal cartilage thickness change was significantly greater in TKAs
      than in non-TKAs in the total femorotibial joint (area under the curve [AUC]
      0.64), the lateral compartment (AUC 0.66), both tibiae (AUC >= 0.61), and the
      first 9 (of 16) ordered values of subregion change (AUC 0.64-0.69).
      Discrimination was stronger for TKAs that occurred at 24 and 36 months (n = 18)
      than for those at 48 and 60 months (n = 22). CONCLUSION: Knees with incident TKA
      displayed smaller baseline cartilage thickness and greater lateral as well as
      location-independent ordered value femorotibial cartilage loss than non-TKAs.
      Discrimination of cartilage loss was greater for TKAs occurring within 2 years
      after the measurement than for those occurring later.

PMID- 25939336
TI  - Explanations of the endowment effect: an integrative review.
AB  - The endowment effect is the tendency for people who own a good to value it more
      than people who do not. Its economic impact is consequential. It creates market
      inefficiencies and irregularities in valuation such as differences between buyers
      and sellers, reluctance to trade, and mere ownership effects. Traditionally, the
      endowment effect has been attributed to loss aversion causing sellers of a good
      to value it more than buyers. New theories and findings--some inconsistent with
      loss aversion--suggest evolutionary, strategic, and more basic cognitive origins.
      In an integrative review, we propose that all three major instantiations of the
      endowment effect are attributable to exogenously and endogenously induced
      cognitive frames that bias which information is accessible during valuation.

PMID- 25939335
TI  - Shared and distinct anatomical correlates of semantic and phonemic fluency
      revealed by lesion-symptom mapping in patients with ischemic stroke.
AB  - Semantic and phonemic fluency tasks are frequently used to test executive
      functioning, speed and attention, and access to the mental lexicon. In semantic
      fluency tasks, subjects are required to generate words belonging to a category
      (e.g., animals) within a limited time window, whereas in phonemic fluency tasks
      subjects have to generate words starting with a given letter. Anatomical
      correlates of semantic and phonemic fluency are currently assumed to overlap in
      left frontal structures, reflecting shared executive processes, and to be
      distinct in left temporal and right frontal structures, reflecting involvement of
      distinct memory processes and search strategies. Definite evidence for this
      assumption is lacking. To further establish the anatomical correlates of semantic
      and phonemic fluency, we applied assumption-free voxel-based and region-of
      interest-based lesion-symptom mapping in 93 patients with ischemic stroke.
      Fluency was assessed by asking patients to name animals (semantic), and words
      starting with the letter N and A (phonemic). Our findings indicate that
      anatomical correlates of semantic and phonemic fluency overlap in the left
      inferior frontal gyrus and insula, reflecting shared underlying cognitive
      processes. Phonemic fluency additionally draws on the left rolandic operculum,
      which might reflect a search through phonological memory, and the middle frontal
      gyrus. Semantic fluency additionally draws on left medial temporal regions,
      probably reflecting a search through semantic memory, and the right inferior
      frontal gyrus, which might reflect the application of a visuospatial mental
      imagery strategy in semantic fluency. These findings establish shared and
      distinct anatomical correlates of semantic and phonemic fluency.

PMID- 25939337
TI  - An uncommon obliterative lung disease: Swyer-James-MacLeod syndrome.

PMID- 25939338
TI  - CHADS2 and CHA2DS2-VASc scores are independently associated with incident atrial
      fibrillation: the Catanzaro Atrial Fibrillation Project.
AB  - No data exist concerning a possible association between CHADS2 or CHA2DS2-VASc
      scores and atrial fibrillation (AF). In this prospective observational study, we
      tested the hypothesis whether thromboembolic risk scores predict AF. We
      investigated 3549 subjects, 1829 men and 1720 women, aged 60.7 +/- 10.6 years,
      without baseline AF. Patients with thyroid disorders were excluded. CHADS2 and
      CHA2DS2-VASc scores were evaluated as categorical variables. To test the effect
      of some clinical confounders on incident AF, we constructed different models
      including clinical and laboratory parameters. During follow-up (53.3 +/- 18.1
      months), 546 subjects developed AF (4.5 events/100 patient-years). Progressors to
      AF are older, have a higher body mass index (BMI), blood pressure, LDL
      cholesterol, and glucose. Hypertension, metabolic syndrome, diabetes and carotid
      wall thickening were more common among AF cases than among control subjects. In
      the final Cox-regression model, variables that remained significantly associated
      with incident AF were BMI (HR = 1.022, 95% CI = 1.008-1.037), LDL-cholesterol (HR
      = 1.032, 95% CI = 1.008-1.056), CHA2DS2-VASc score (HR = 1.914, 95% CI = 1.439
      2.546), and CHADS2 score (HR = 2.077, 95% CI = 1.712-2.521). In conclusion,
      CHADS2 and CHA2DS2-VASc scores are independent predictors of AF.

PMID- 25939339
TI  - 10 years later: assessing the impact of public health efforts on the collection
      of family health history.
AB  - In 2004, a nationwide survey found that the majority (96.3%) of Americans
      believed their family health history (FHx) was important for their own health;
      however, only a third (29.8%) of respondents had ever actively collected this
      information. Over the past decade, government agencies, advocacy groups,
      professional societies, and healthcare provider organizations have aimed to
      improve the collection rates and utilization of FHx. This study assesses the
      current attitudes, knowledge, and practices of Americans regarding their FHx and
      whether the interventions over the past 10 years have led to any FHx-related
      changes. We conducted a nationwide survey of 5,258 respondents using the same
      measures used in the 2004 survey. Overall, there was little change in Americans
      knowledge and use of FHx information. While there was a statistically significant
      increase in respondents who have actively collected their FHx (36.9%),
      respondents know roughly the same or less about his or her FHx today.
      Furthermore, only a small fraction (2.6%) had ever collected their FHx using a
      web-based FHx tool. Several factors were identified which influence whether an
      individual actively collects his or her FHx. New FHx tools and approaches may be
      necessary to promote clinically meaningful improvement in FHx collection among
      patients.

PMID- 25939341
TI  - Interaction of polyacrylic acid with lipid bilayers: effect of polymer mass.
AB  - Polyanion-coated lipid vesicles are proposed to have an appreciable potential for
      drug delivery because of their ability to control the permeability of lipid
      bilayers by environmental parameters such as pH and temperature. However, details
      of the interaction of this class of polymers with lipids and their mechanisms of
      induced permeability are still being debated. In this work, we applied (1)H NOESY
      to study details of the interaction of polyacrylic acid (PAA) fractions of
      molecular weights 5 and 240 kDa with dimyristoylphosphatidylcholine vesicles. We
      showed that PAA of two different molecular masses modifies lipid bilayers
      increasing disorder and probability of close contact between polar and
      hydrophobic groups. PAA molecules adsorb near the interface of lipid bilayers but
      do not penetrate into the hydrophobic core of the bilayer and, thus, cannot
      participate in formation of transbilayer channels, proposed in earlier works.
      Increasing the molecular mass of PAA from 5 kDa to 240 kDa does not change the
      effect of PAA on the bilayer, although PAA240 forms a more compact structure
      (either intra-molecular or inter-molecular) and interacts more strongly with
      interface lipid protons.

PMID- 25939342
TI  - Gold Nanocluster Embedded Albumin Nanoparticles for Two-Photon Imaging of Cancer
      Cells Accompanying Drug Delivery.
AB  - Gold nanoclusters in albumin nanoparticles (nanovehicles) are used for single
      photon and two-photon imaging of cancer cells following the delivery of
      doxorubicin through the nanovehicle. NIR excitation and emission wavelengths in
      the biological window (650-900 nm) make the nanovehicle an ideal potential
      platform for imaging guided drug delivery. 

PMID- 25939343
TI  - Defining the nasal transcriptome in granulomatosis with polyangiitis (Wegener's).
AB  - OBJECTIVE: To determine whether disease processes related to granulomatosis with
      polyangiitis (Wegener's) (GPA) are reflected in gene expression profiles of the
      nasal mucosa. METHODS: Nasal brushings of the inferior turbinate were obtained
      from 32 patients with GPA (10 with active nasal disease, 13 with prior nasal
      disease, and 9 with no history of nasal disease) and a composite comparator group
      with and without inflammatory nasal disease (12 healthy people, 15 with
      sarcoidosis, and 8 with allergic rhinitis). Differential gene expression was
      assessed between subgroups of GPA and comparators. RESULTS: A total of 339 genes
      were differentially expressed between the GPA and comparator groups (absolute
      fold change >1.5; false discovery rate <0.05). Top canonical pathways up
      regulated in nasal brushings from patients with GPA included granulocyte adhesion
      and diapedesis (P = 8.6(-22) ), agranulocyte adhesion and diapedesis (P = 1.3(
      14) ), IL10 signaling (P = 3.0(-11) ), LXR/RXR activation (P = 4.3(-11) ), and
      TREM1 signaling (P = 9.0(-11) ). A set of genes differentially expressed in GPA
      independently of nasal disease activity status included genes related to
      epithelial barrier integrity (fibronectin 1, desmosomal proteins) and several
      matricellular proteins (e.g., osteonectin, osteopontin). Significant overlap of
      differentially expressed genes was observed between active and prior nasal
      disease GPA subgroups. Peripheral blood neutrophil and mononuclear gene
      expression levels associated with GPA were similarly altered in the nasal gene
      expression profiles of patients with active or prior nasal disease. CONCLUSION:
      Profiling the nasal transcriptome in GPA reveals gene expression signatures
      related to innate immunity, inflammatory cell chemotaxis, extracellular matrix
      composition, and epithelial barrier integrity. Thus, airway-based expression
      profiling is feasible and informative in GPA.

PMID- 25939344
TI  - Therapeutic Effect of Supercritical CO2 Extracts of Curcuma Species with Cancer
      Drugs in Rhabdomyosarcoma Cell Lines.
AB  - Synergistic effect of supercritical CO2 extracts of Curcuma species with
      conventional chemotherapeutic drugs was investigated in human alveolar (SJRH30)
      and embryonal (RD) rhabdomyosarcoma cell lines. The Curcuma amada (mango ginger)
      (CA) extract showed the highest levels of cytotoxicity with inhibitory
      concentration IC50 values of 7.133 ug/ml and 7.501 ug/ml for SJRH30 and RD cell
      lines, respectively, as compared with Curcuma longa (turmeric) and Curcuma
      xanthorrhiza (Javanese turmeric) extracts. CA showed synergistic cytotoxic
      effects with vinblastine (VBL) and cyclophosphamide (CP) as indicated by the
      combination index values of <1 for VBL + CA, CP + CA, and VBL + CP + CA
      combinations in both embryonal and alveolar rhabdomyosarcomas. When lower doses
      of CA (0.1-0.2 ug/ml) were combined with cancer drugs like CP and VBL, caspase-3
      activity increased significantly compared with individual agents and correlated
      with the percentage of apoptotic cells. CA in combination with VBL and CP induced
      a higher percentage of apoptosis than single agents in both cell lines. CA also
      modulated the expression of genes associated with intrinsic pathway of apoptosis
      (Bcl-2, Bax, Bak, and p53) and also inhibited the expression of genes associated
      with inflammation such as COX-2 and NF-kappaB. Xenograft studies with SJRH30
      tumors in nude mice showed that CA treatment inhibited tumor growth rate with and
      without VBL and increased the survival rate significantly. These results suggest
      that CA can be evaluated further as an adjuvant with cancer drugs for the
      treatment of rhabdomyosarcoma patients. Copyright (c) 2015 John Wiley & Sons,
      Ltd.

PMID- 25939345
TI  - Ferenc A. Jolesz (1946-2014).

PMID- 25939347
TI  - In Vivo Antineoplastic Effects of the NSAID Sulindac in an Oral Carcinogenesis
      Model.
AB  - The antineoplastic properties of the NSAID sulindac have long been studied. The
      purpose of this study was to explore sulindac's in vivo effects on oral squamous
      cell carcinoma (SCC) oncogenesis using the hamster cheek pouch oral
      carcinogenesis model (HOCM). Thirty Syrian golden hamsters were divided into
      three experimental and two control groups (n = 6 each). The animals' right buccal
      pouches were treated with carcinogen for 9 weeks in one experimental and one
      control group and for 14 weeks in all other three groups. The animals of two
      experimental groups received sulindac from the 1st week and those of the third
      experimental group from the 10th week. After the end of carcinogenesis, treated
      buccal pouches were removed and examined. In animals treated with carcinogen for
      14 weeks, development of oral SCC and tumor volume were significantly lower in
      animals that received sulindac from the first week of the experiment. Oral SCC
      developing in animals that received sulindac were more frequently well
      differentiated compared with the control group. In animals treated with
      carcinogen for 9 weeks, the animals that received sulindac developed lower grade
      of epithelial dysplasia. Proliferation index Ki-67 and positivity for the
      antiapoptotic molecule survivin were lower in the animals that received sulindac.
      Treatment with sulindac appears to delays the progression of oral premalignant
      lesions to oral SCC in the HOCM, also resulting in smaller and better
      differentiated tumors. These in vivo antineoplastic effects may be related to
      sulindac's ability to decrease cell proliferation and to prevent survivin
      expression.

PMID- 25939346
TI  - Restrictive and liberal red cell transfusion strategies in adult patients:
      reconciling clinical data with best practice.
AB  - Red blood cell (RBC) transfusion guidelines correctly promote a general
      restrictive transfusion approach for anemic hospitalized patients. Such
      recommendations have been derived from evaluation of specific patient
      populations, and it is important to recognize that engaging a strict guideline
      approach has the potential to incur harm if the clinician fails to provide a
      comprehensive review of the patient's physiological status in determining the
      benefit and risks of transfusion. We reviewed the data in support of a
      restrictive or a more liberal RBC transfusion practice, and examined the quality
      of the datasets and manner of their interpretation to provide better context by
      which a physician can make a sound decision regarding RBC transfusion therapy.
      Reviewed studies included PubMed-cited (1974 to 2013) prospective randomized
      clinical trials, prospective subset analyses of randomized studies, nonrandomized
      controlled trials, observational case series, consecutive and nonconsecutive case
      series, and review articles. Prospective randomized clinical trials were
      acknowledged and emphasized as the best-quality evidence. The results of the
      analysis support that restrictive RBC transfusion practices appear safe in the
      hospitalized populations studied, although patients with acute coronary
      syndromes, traumatic brain injury and patients at risk for brain or spinal cord
      ischemia were not well represented in the reviewed studies. The lack of quality
      data regarding the purported adverse effects of RBC transfusion at best suggests
      that restrictive strategies are no worse than liberal strategies under the
      studied protocol conditions, and RBC transfusion therapy in the majority of
      instances represents a marker for greater severity of illness. The conclusion is
      that in the majority of clinical settings a restrictive RBC transfusion strategy
      is cost-effective, reduces the risk of adverse events specific to transfusion,
      and introduces no harm. In anemic patients with ongoing hemorrhage, with risk of
      significant bleeding, or with concurrent ischemic brain, spinal cord, or
      myocardium, the optimal hemoglobin transfusion trigger remains unknown. Broad
      based adherence to guideline approaches of therapy must respect the individual
      patient condition as interpreted by comprehensive clinical review. 

PMID- 25939349
TI  - Groundwater pesticide levels and the association with Parkinson disease.
AB  - It is unclear whether exposure to environmentally relevant levels of pesticides
      in groundwater is associated with an increased risk of Parkinson disease (PD).
      The purpose of this study was to examine the relationship between PD and
      pesticide levels in groundwater. This cross-sectional study included 332 971
      Medicare beneficiaries, including 4207 prevalent cases of PD from the 2007
      Colorado Medicare Beneficiary Database. Residential pesticide levels were
      estimated from a spatial model based on 286 well water samples with atrazine,
      simazine, alachlor, and metolachlor measurements. A logistic regression model
      with known PD risk factors was used to assess the association between residential
      groundwater pesticide levels and prevalent PD. We found that for every 1.0 ug/L
      of pesticide in groundwater, the risk of PD increases by 3% (odds ratio = 1.03;
      95% confidence interval: 1.02-1.04) while adjusting for age, race/ethnicity, and
      gender suggesting that higher age-standardized PD prevalence ratios are
      associated with increasing levels of pesticides in groundwater. 

PMID- 25939348
TI  - Polybrominated diphenyl ethers and thyroid cancer risk in the Prostate,
      Colorectal, Lung, and Ovarian Cancer Screening Trial cohort.
AB  - Polybrominated diphenyl ethers (PBDEs) alter thyroid hormone homeostasis, but
      their relationship with thyroid cancer is unknown. To investigate whether serum
      concentrations of PBDE were associated with thyroid cancer, we conducted a
      nested, case-control study in the Prostate, Lung, Colorectal, and Ovarian Cancer
      Screening Trial, a large multicenter clinical trial in the United States. Cases
      with thyroid cancer (n = 104) were recruited from 1992 to 2001 and diagnosed
      through 2009, and controls (n = 208) were individually matched (2:1) to cases by
      race, sex, birth date (within 1 year), center, and blood collection date (within
      15 days). We used gas chromatography isotope dilution high-resolution mass
      spectrometry to measure 10 tri- to heptabrominated diphenyl eithers in serum
      samples. Odds ratios and 95% confidence intervals were calculated using
      conditional logistic regression for lipid-adjusted PBDE levels detected in more
      than 50% of controls and for the sum of these BDEs (?PBDEs). We observed no
      significant differences between cases and controls in lipid-adjusted
      concentrations of ?PBDEs (for cases, median = 12.8 ng/g lipid (interquartile
      range, 6.2-42.1); for controls, median = 19.4 ng/g lipid (interquartile range,
      7.6-50.2)) or for individual congeners. Increasing quartiles of ?PBDEs and 4 BDE
      congeners were not associated with risk of thyroid cancer (for the fourth vs.
      first quartile of ?PBDEs, adjusted odd ratio = 0.62, 95% confidence interval:
      0.29, 1.30; P for trend = 0.56). Our study does not support an association
      between exposure to PBDEs and thyroid cancer. 

PMID- 25939350
TI  - A 4-week toxicity study of methionine in male rats.
AB  - To examine 4-week toxicity of l-methionine (methionine), 5-week-old Fisher strain
      male rats were fed on diets containing 0, 0.1, 0.3, 0.9, 2.7 (w/w) of added
      methionine. Although no deaths were recorded, the highest dose of methionine
      (2.7% [w/w] of diet) reduced food intake and significantly suppressed growth
      rate. Growth suppression was characterized by an increase in hemolysis, splenic,
      and hepatic accumulation of hemosiderin, hemolytic anemia, and promotion of
      hematopoiesis. Other changes observed in the highest methionine intake group were
      a decrease in white blood cell count, thymus atrophy, and histological
      abnormalities in the adrenal gland and testis. Small, but significant, growth
      suppression, accompanied by some minor changes in plasma biochemical parameters,
      was also seen in rats fed on a test diet containing 0.9% (w/w) of additional
      methionine. Thus, no-observed-adverse-effect-level (NOAEL) and lowest-observed
      adverse-effect level (LOAEL) of diet-added methionine were determined at 0.3% and
      0.9% (w/w), corresponding to 236 and 705 mg/kg/d body weight, respectively. Since
      the basal diet contained protein-bound methionine at 0.5% (w/w), NOAEL and LOAEL
      of total dietary methionine were estimated at 0.8% and 1.4% (w/w) of diet. 

PMID- 25939351
TI  - Successful Pregnancies with Thiopurine-Allopurinol Co-Therapy for Inflammatory
      Bowel Disease.
AB  - BACKGROUND: Thiopurines are an effective treatment for moderate to severe
      inflammatory bowel disease [IBD] and can be used safely in pregnancy. Combining
      allopurinol with a lower dose of thiopurine can improve clinical efficacy and
      bypass some adverse reactions associated with thiopurine monotherapy. Data on
      allopurinol in pregnancy are scarce. We report on a total of 13 cases where
      thiopurine and allopurinol co-therapy was used successfully to manage IBD during
      pregnancy without attributable adverse fetal effects. METHODS: Patients were
      retrospectively identified at our two hospitals, one in the UK and one in
      Australia, using local IBD databases. Data regarding pregnancy and fetal outcomes
      including in utero fetal ultrasound scans, APGAR scores, fetal birthweights and
      neonate checks were collected from patient notes. RESULTS: We identified 12 women
      with a total of 13 pregnancies treated with co-therapy before conception and for
      the duration of pregnancy. There were no miscarriages or spontaneous pre-term
      deliveries. There were 14 live births [seven vaginal deliveries; six caesarean
      sections]. Except for a primagravid twin pregnancy complicated by pre-eclampsia
      and twin-to-twin transfusion syndrome requiring caesarean section at 25 weeks,
      there were no low birthweight [< 2.5 kg] babies born and the APGAR scores of all
      babies were normal. No congenital malformations were identified. CONCLUSIONS:
      Adverse pregnancy outcomes attributable to thiopurine and allopurinol co-therapy
      were not detected in our case series. Our study provides reassurance for
      clinicians and patients who wish to continue the thiopurine-allopurinol co
      therapy combination before conception and during pregnancy to maintain remission
      of IBD.

PMID- 25939352
TI  - A prospective study of the safety of lower gastrointestinal endoscopy during
      pregnancy in patients with inflammatory bowel disease.
AB  - INTRODUCTION: Women with inflammatory bowel disease [IBD] have a higher risk of
      undergoing gastrointestinal [GI] endoscopy during pregnancy than healthy women.
      Data on endoscopic procedures during pregnancy in IBD women are limited. The aim
      of this study was to investigate the safety of lower GI endoscopy during
      pregnancy in IBD women. METHODS: All consecutive IBD women who underwent
      endoscopy during pregnancy [cases] from 2008-2014 were prospectively included.
      Cases were matched 1:1 on age, IBD medication, and disease activity with pregnant
      IBD patients without endoscopy during pregnancy [controls]. Maternal and neonatal
      outcomes were compared between the cases and controls. Adverse events [AEs] were
      assessed for a temporal relation and for an aetiological relation with the
      endoscopy. RESULTS: In total, 42 pregnant IBD patients [19 Crohn's disease, 23
      ulcerative colitis] underwent 47 lower GI endoscopies [12 colonoscopies/35
      sigmoidoscopies]. Median maternal age was 30 years [interquartile range: 28-32].
      Two spontaneous abortions were temporally and probably related to endoscopy;
      however, spontaneous abortion did not occur more often in cases than in controls
      (2 [4.8%] vs 10 [23.8%], p 0.01). Median birthweight was significantly lower in
      the cases compared with controls [3017g vs 3495g, p 0.01]. There were no
      significant differences in terms of gestational age at birth, congenital
      abnormalities, or APGAR scores. CONCLUSION: Although lower GI endoscopy in
      pregnant IBD women should only be performed when strongly indicated, we report no
      increased adverse outcomes for the mother or the newborn related to endoscopy in
      any of the three trimesters of pregnancy compared with controls.

PMID- 25939353
TI  - Expression and localization of urokinase-type plasminogen activator receptor in
      bovine cumulus-oocyte complexes.
AB  - Urokinase-type plasminogen activator (uPA) is a serine protease involved in
      extracellular matrix remodeling through plasmin generation. uPA usually binds to
      its receptor, uPAR, which is anchored to the plasma membrane through a
      glycosylphosphatidylinositol anchor. uPA/uPAR binding increases proteolytic
      activity in the neighborhood of the cells containing uPAR and activates
      intracellular signaling pathways involved in extracellular matrix remodeling,
      cell migration and proliferation. The aim of this work was to study the
      expression of uPA, uPAR and plasminogen activator inhibitor-1 (PAI-1) in immature
      and in vitro matured bovine cumulus-oocyte complexes (COCs). uPA is only
      expressed in the cumulus cells of immature and in vitro matured COCs, while uPAR
      and PAI-1 are expressed in both the cumulus cells and the immature and in vitro
      matured oocytes. In addition, uPAR protein was localized by confocal microscopy
      in the plasma membrane of oocytes and cumulus cells of immature COCs. Results
      from this research led us to hypothesize that the uPA/uPAR interaction could
      cause the local production of uPA-mediated plasmin over oocyte and cumulus cell
      surface; plasmin formation could also be regulated by PAI-1. 

PMID- 25939355
TI  - Syntheses and reductions of C-dimesitylboryl-1,2-dicarba-closo-dodecaboranes.
AB  - Two C-dimesitylboryl-1,2-dicarba-closo-dodecaboranes, 1-(BMes2)-2-R-1,2-C2B10H10
      (1, R = H, 2, R = Ph), were synthesised by lithiation of 1,2-dicarba-closo
      dodecaborane and 1-phenyl-1,2-dicarba-closo-dodecaborane, respectively, with n
      butyllithium and subsequent reaction with fluorodimesitylborane. These novel
      compounds were structurally characterised by X-ray crystallography. Compounds 1
      and 2 are hydrolysed on prolonged exposure to air to give mesitylene and boronic
      acids 1-(B(OH)2)-2-R-1,2-C2B10H10 (3, R = H, 4, R = Ph respectively). Addition of
      fluoride anions to 1 and 2 resulted in boryl-carborane bond cleavage to give
      dimesitylborinic acid HOBMes2. UV absorption bands at 318-333 nm were observed
      for 1 and 2 corresponding to local pi-pi*-transitions within the dimesitylboryl
      groups while visible emissions at 541-664 nm with Stokes shifts of 11 920-16 170
      cm(-1) were attributed to intramolecular charge transfer transitions between the
      mesityl and cluster groups. Compound was shown by cyclic voltammetry to form a
      stable dianion on reduction. NMR spectra for the dianion [](2-) were recorded
      from solutions generated by reductions of 2 with alkali metals and compared with
      NMR spectra from reductions of 1,2-diphenyl-ortho-carborane 5. On the basis of
      observed and computed (11)B NMR shifts, these nido-dianions contain bowl-shaped
      cluster geometries. The carborane is viewed as the electron-acceptor and the
      mesityl group is the electron-donor in C-dimesitylboryl-1,2-dicarba-closo
      dodecaboranes.

PMID- 25939356
TI  - Broadband optical limiting response of a graphene-PbS nanohybrid.
AB  - Graphene-based materials have shown promising nonlinear optical properties in the
      visible range. To extend their nonlinear optical response to the near infrared
      (NIR) region, we prepared a new nanohybrid consisting of uniform PbS quantum dots
      (QDs) attached on the reduced graphene oxide, named rGO-PbS, via a facile, low
      cost, and phosphine-free method. The rGO-PbS nanohybrid exhibited superior
      optical limiting properties to either graphene oxide or PbS QDs upon both 532 nm
      and 1064 nm excitation in the nanosecond laser pulse regime, which is attributed
      to the synergetic effects stemming from charge transfer between the two
      components. Meanwhile, the thin films containing the rGO-PbS nanohybrid dispersed
      in polymethylmethacrylate (PMMA) also showed excellent optical limiting
      properties with high transparency, implying the potential applications of this
      hybrid material in broadband nonlinear optical devices. 

PMID- 25939354
TI  - DNA methylation in Arabidopsis has a genetic basis and shows evidence of local
      adaptation.
AB  - Epigenome modulation potentially provides a mechanism for organisms to adapt,
      within and between generations. However, neither the extent to which this occurs,
      nor the mechanisms involved are known. Here we investigate DNA methylation
      variation in Swedish Arabidopsis thaliana accessions grown at two different
      temperatures. Environmental effects were limited to transposons, where CHH
      methylation was found to increase with temperature. Genome-wide association
      studies (GWAS) revealed that the extensive CHH methylation variation was strongly
      associated with genetic variants in both cis and trans, including a major trans
      association close to the DNA methyltransferase CMT2. Unlike CHH methylation, CpG
      gene body methylation (GBM) was not affected by growth temperature, but was
      instead correlated with the latitude of origin. Accessions from colder regions
      had higher levels of GBM for a significant fraction of the genome, and this was
      associated with increased transcription for the genes affected. GWAS revealed
      that this effect was largely due to trans-acting loci, many of which showed
      evidence of local adaptation. 

PMID- 25939357
TI  - Non-invasive assessment of endothelial function in children with obesity and
      lipid disorders.
AB  - BACKGROUND: Digital tonometry is designed to non-invasively screen for
      endothelial dysfunction by the detection of impaired flow-induced reactive
      hyperaemia in the fingertip. We determined whether digital reactive hyperaemia
      correlated with risk factors for atherosclerosis in two groups of children at
      increased risk for endothelial dysfunction. METHODS: A total of 15 obese children
      and 23 non-obese, dyslipidaemic children, 8-21 years of age, were enrolled, and
      their medical histories, anthropometric measurements, carotid wall thickness by
      means of ultrasonography, and fasting blood samples for cardiovascular risk
      factors were obtained. The standard endoPAT index of digital reactive hyperaemia
      was modified to reflect the true peak response or the integrated response of the
      entire post-occlusion period. In each group, age, sex, pubertal status, carotid
      wall thickness, and multiple cardiovascular risk factors were tested as
      predictors of endothelial dysfunction. RESULTS: In the non-obese, dyslipidaemic
      group, but not in the obese group, both indices strongly correlated with height
      (r=0.55, p=0.007, by peak response) followed by weight, waist circumference, and
      age. In both groups, neither index of reactive hyperaemia significantly
      correlated with any other cardiovascular risk factor. CONCLUSIONS: Contrary to
      the known age-related increase in atherosclerosis, digital reactive hyperaemia
      increased with age and its correlates in non-obese, dyslipidaemic children and
      was not related to other cardiovascular risk factors in either group. The reason
      for the lack of this relationship with age in obese children is unknown. The age
      dependent physiology of digital microvascular reactivity and the endothelium
      independent factors controlling the peak hyperaemic response need further study
      in children with a wide age range.

PMID- 25939359
TI  - The reliability and validity of the Complex Task Performance Assessment: A
      performance-based assessment of executive function.
AB  - The objective of this study was to evaluate the inter-rater reliability, test
      retest reliability, concurrent validity, and discriminant validity of the Complex
      Task Performance Assessment (CTPA): an ecologically valid performance-based
      assessment of executive function. Community control participants (n = 20) and
      individuals with mild stroke (n = 14) participated in this study. All
      participants completed the CTPA and a battery of cognitive assessments at initial
      testing. The control participants completed the CTPA at two different times one
      week apart. The intra-class correlation coefficient (ICC) for inter-rater
      reliability for the total score on the CTPA was .991. The ICCs for all of the sub
      scores of the CTPA were also high (.889-.977). The CTPA total score was
      significantly correlated to Condition 4 of the DKEFS Color-Word Interference Test
      (p = -.425), and the Wechsler Test of Adult Reading (p  = -.493). Finally, there
      were significant differences between control subjects and individuals with mild
      stroke on the total score of the CTPA (p = .007) and all sub-scores except
      interpretation failures and total items incorrect. These results are also
      consistent with other current executive function performance-based assessments
      and indicate that the CTPA is a reliable and valid performance-based measure of
      executive function.

PMID- 25939360
TI  - The role of charge transfer in the oxidation state change of Ce atoms in the TM13
      CeO2(111) systems (TM = Pd, Ag, Pt, Au): a DFT + U investigation.
AB  - Despite extensive studies of transition metal (TM) clusters supported on ceria
      (CeO2), fundamental issues such as the role of the TM atoms in the change in the
      oxidation state of Ce atoms are still not well understood. In this work, we
      report a theoretical investigation based on static and ab initio molecular
      dynamics density functional theory calculations of the interaction of 13-atom TM
      clusters (TM = Pd, Ag, Pt, Au) with the unreduced CeO2(111) surface represented
      by a large surface unit cell and employing Hubbard corrections for the strong on
      site Coulomb correlation in the Ce f-electrons. We found that the TM13 clusters
      form pyramidal-like structures on CeO2(111) in the lowest energy configurations
      with the following stacking sequence, TM/TM4/TM8/CeO2(111), while TM13 adopts two
      dimensional structures at high energy structures. TM13 induces a change in the
      oxidation state of few Ce atoms (3 of 16) located in the topmost Ce layer from
      Ce(IV) (itinerant Ce f-states) to Ce(III) (localized Ce f-states). There is a
      charge flow from the TM atoms to the CeO2(111) surface, which can be explained by
      the electronegativity difference between the TM (Pd, Ag, Pt, Au) and O atoms,
      however, the charge is not uniformly distributed on the topmost O layer due to
      the pressure induced by the TM13 clusters on the underlying O ions, which yields
      a decrease in the ionic charge of the O ions located below the cluster and an
      increase in the remaining O ions. Due to the charge flow mainly from the TM8
      layer to the topmost O-layer, the charge cannot flow from the Ce(IV) atoms to the
      O atoms with the same magnitude as in the clean CeO2(111) surface. Consequently,
      the effective cationic charge decreases mainly for the Ce atoms that have a bond
      with the O atoms not located below the cluster, and hence, those Ce atoms change
      their oxidation state from IV to III. This increases the size of the Ce(III)
      compared with the Ce(IV) cations, which builds-in a strain within the topmost Ce
      layer, and hence, also affecting the location of the Ce(III) cations and the
      structure of the TM13 clusters. 

PMID- 25939361
TI  - Epigenetics in the wild.
AB  - Studies of wild populations of the model plant Arabidopsis thaliana have started
      to reveal how patterns of DNA methylation change in response to the local
      environment. 

PMID- 25939362
TI  - Controlling and prevention of surface wrinkling via size-dependent critical
      wrinkling strain.
AB  - Surface wrinkling may occur in a film-substrate system when the applied strain
      exceeds the critical value. However, the practically required strain for the
      onset of surface wrinkling can be different from the theoretically predicted
      value. Here we investigate the film size effect-dependent critical strain for the
      mechanical strain-induced surface wrinkling via a combination of experiments and
      theoretical analysis. In the poly(dimethylsiloxane)-based system fabricated by
      the smart combination of mechanical straining and selective O2 plasma (OP)
      exposure through Cu grids, the film size effect on the critical wrinkling strain
      is systematically studied by considering OP exposure duration, the mesh number
      and geometry of Cu grids. Meanwhile, a simple analytical solution revealing the
      film size effect is well established, which shows good consistency with the
      experimental results. This study provides an experimental and theoretical basis
      for finely tuning the critical wrinkling strain in a simple and quantitative
      manner, which can find a wide range of applications in such fields as
      microelectronic circuits and optical devices, where controlling and/or prevention
      of surface wrinkling are of great importance. 

PMID- 25939363
TI  - Absolute Arrangement of Subunits in Cytoskeletal Septin Filaments in Cells
      Measured by Fluorescence Microscopy.
AB  - We resolved the organization of subunits in cytoskeletal polymers in cells by
      light microscopy. Septin GTPases form linear complexes of about 32 nm length that
      polymerize into filaments. We visualized both termini of septin complexes by
      single molecule microscopy in vitro. Complexes appeared as 32 nm spaced
      localization pairs, and filaments appeared as stretches of equidistant
      localizations. Cellular septins were resolved as localization pairs and thin
      stretches of equidistant localizations. 

PMID- 25939364
TI  - FOAMSearch.net: A custom search engine for emergency medicine and critical care.
AB  - The number of online resources read by and pertinent to clinicians has increased
      dramatically. However, most healthcare professionals still use mainstream search
      engines as their primary port of entry to the resources on the Internet. These
      search engines use algorithms that do not make it easy to find clinician-oriented
      resources. FOAMSearch, a custom search engine (CSE), was developed to find
      relevant, high-quality online resources for emergency medicine and critical care
      (EMCC) clinicians. Using GoogleTM algorithms, it searches a vetted list of >300
      blogs, podcasts, wikis, knowledge translation tools, clinical decision support
      tools and medical journals. Utilisation has increased progressively to >3000
      users/month since its launch in 2011. Further study of the role of CSEs to find
      medical resources is needed, and it might be possible to develop similar CSEs for
      other areas of medicine.

PMID- 25939365
TI  - Equivalence of kernel machine regression and kernel distance covariance for
      multidimensional phenotype association studies.
AB  - Associating genetic markers with a multidimensional phenotype is an important yet
      challenging problem. In this work, we establish the equivalence between two
      popular methods: kernel-machine regression (KMR), and kernel distance covariance
      (KDC). KMR is a semiparametric regression framework that models covariate effects
      parametrically and genetic markers non-parametrically, while KDC represents a
      class of methods that include distance covariance (DC) and Hilbert-Schmidt
      independence criterion (HSIC), which are nonparametric tests of independence. We
      show that the equivalence between the score test of KMR and the KDC statistic
      under certain conditions can lead to a novel generalization of the KDC test that
      incorporates covariates. Our contributions are 3-fold: (1) establishing the
      equivalence between KMR and KDC; (2) showing that the principles of KMR can be
      applied to the interpretation of KDC; (3) the development of a broader class of
      KDC statistics, where the class members are statistics corresponding to different
      kernel combinations. Finally, we perform simulation studies and an analysis of
      real data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. The
      ADNI study suggest that SNPs of FLJ16124 exhibit pairwise interaction effects
      that are strongly correlated to the changes of brain region volumes. 

PMID- 25939366
TI  - The first national tuberculosis prevalence survey of Lao PDR (2010-2011).
AB  - OBJECTIVE: The objective of the study was to measure the prevalence of
      bacteriologically confirmed pulmonary tuberculosis (TB) in Lao PDR in 2010-2011.
      METHOD: A nationwide, multistage cluster-sampled cross-sectional survey was
      undertaken in 2010-2011. All consenting participants >=15 years were screened for
      pulmonary TB with chest X-ray and symptom questionnaire. Two sputum specimens for
      bacteriological examination by microscopy and culture were collected from those
      who screened positive. Prevalence was estimated using multiple imputation and
      inverse probability weighting methods. RESULTS: Of 39 212 eligible participants
      from 50 clusters, 6290 participants provided at least one sputum sample for smear
      and culture. There were 237 bacteriologically confirmed pulmonary TB cases, 107
      of which were smear-positive. Chest X-ray screening alone identified 230 (97.0%)
      cases compared with 118 (49.8%) by symptom screening alone. The estimated
      prevalence of smear-positive and bacteriologically confirmed TB in those >=15
      years was 278 per 100 000 (95%C.I. 199-356) and 595 per 100 000 (95%C.I. 457
      733), respectively. Prevalence significantly increased with age and was higher in
      men than women. CONCLUSIONS: The prevalence of TB in Lao PDR is almost twice as
      high than previous estimates, with the greatest burden in the older population.
      Case detection efforts remain the primary goal of the national TB programme with
      case notifications being very low in comparison with the estimated number of
      prevalent cases. The survey observed major limitations with the diagnostic
      strategy of passive (symptom based) case finding that uses only direct smear
      microscopy for confirmation.

PMID- 25939367
TI  - COX inhibition reduces vasodilator PGE2 but is shown to increase levels of
      chemoattractant 12-HETE in vivo in human sunburn.

PMID- 25939369
TI  - Engaging with culturally and linguistically diverse communities to reduce the
      impact of depression and anxiety: a narrative review.
AB  - Culturally and linguistically diverse (CALD) communities in Australia face
      significant challenges in terms of reducing barriers to information and support
      for depression and anxiety. Increased stigma surrounding mental ill-health in
      some cultures and related concerns about trust and confidentiality all impact
      upon timely access to information, services and support for consumers and carers
      from CALD backgrounds. For health services, there is a need to understand how to
      better engage CALD communities in mental healthcare. The objective of this
      narrative review was to identify examples of evidence-based, best practice for
      what works effectively for engaging with CALD communities to reduce the impact of
      depression and anxiety. In January 2014, we searched Academic Search Premier,
      CINAHL, Health-Source Consumer Edition, PsycARTICLES, PsycINFO (all databases
      within the EbscoHost platform) and PubMed for peer-reviewed articles published
      between 1994 and 2014. The search revealed a total of 706 records contained
      within the EbscoHost platform and 689 records in PubMed; 15 matched the inclusion
      criteria. Six key themes were identified: (i) setting the scene for engagement;
      (ii) cultural values and preferences; (iii) language considerations; (iv)
      'engagers' in the therapeutic process; (v) opening out engagement to include
      others; and (vi) engaging through the use of technology and alternative mediums.
      The literature obtained provides a small body of evidence regarding approaches to
      engaging CALD communities, with findings highlighting the importance of processes
      which are tailored to the CALD community of interest and which take into account
      different cultural explanatory models of mental ill-health. Review findings are
      also discussed within the framework of intersectionality, in which broader
      structural inequalities and power imbalances - in areas such as gender and social
      class - collectively impact on help-seeking and mental health outcomes. This
      review supports further enquiry into how such societal issues influence
      engagement - and disengagement - in mental health services for CALD communities.

PMID- 25939371
TI  - The influence of surface soil physicochemistry on the edaphic bacterial
      communities in contrasting terrain types of the Central Namib Desert.
AB  - Notwithstanding, the severe environmental conditions, deserts harbour a high
      diversity of adapted micro-organisms. In such oligotrophic environments, soil
      physicochemical characteristics play an important role in shaping indigenous
      microbial communities. This study investigates the edaphic bacterial communities
      of three contrasting desert terrain types (gravel plains, sand dunes and
      ephemeral rivers) with different surface geologies in the Central Namib Desert.
      For each site, we evaluated surface soil physicochemistries and used explorative
      T-RFLP methodology to get an indication of bacterial community diversities. While
      grain size was an important parameter in separating the three terrain types
      physicochemically and specific surface soil types could be distinguished, the
      desert edaphic bacterial communities displayed a high level of local spatial
      heterogeneity. Ten variables contributed significantly (P < 0.05) to the variance
      in the T-RFLP data sets: fine silt, medium and fine sand content, pH, S, Na, Zn,
      Al, V and Fe concentrations, and 40% of the total variance could be explained by
      these constraining variables. The results suggest that local physicochemical
      conditions play a significant role in shaping the bacterial structures in the
      Central Namib Desert and stress the importance of recording a wide variety of
      environmental descriptors to comprehensively assess the role of edaphic
      parameters in shaping microbial communities. 

PMID- 25939370
TI  - Elucidating steroid alkaloid biosynthesis in Veratrum californicum: production of
      verazine in Sf9 cells.
AB  - Steroid alkaloids have been shown to elicit a wide range of pharmacological
      effects that include anticancer and antifungal activities. Understanding the
      biosynthesis of these molecules is essential to bioengineering for sustainable
      production. Herein, we investigate the biosynthetic pathway to cyclopamine, a
      steroid alkaloid that shows promising antineoplastic activities. Supply of
      cyclopamine is limited, as the current source is solely derived from wild
      collection of the plant Veratrum californicum. To elucidate the early stages of
      the pathway to cyclopamine, we interrogated a V. californicum RNA-seq dataset
      using the cyclopamine accumulation profile as a predefined model for gene
      expression with the pattern-matching algorithm Haystack. Refactoring candidate
      genes in Sf9 insect cells led to discovery of four enzymes that catalyze the
      first six steps in steroid alkaloid biosynthesis to produce verazine, a predicted
      precursor to cyclopamine. Three of the enzymes are cytochromes P450 while the
      fourth is a gamma-aminobutyrate transaminase; together they produce verazine from
      cholesterol. 

PMID- 25939372
TI  - Examination of a dual-process model predicting riding with drinking drivers.
AB  - BACKGROUND: Nearly 1 in 5 of the fatalities in alcohol-related crashes are
      passengers. Few studies have utilized theory to examine modifiable psychosocial
      predictors of individuals' tendencies to be a passenger in a vehicle operated by
      a driver who has consumed alcohol. This study used a prospective design to test a
      dual-process model featuring reasoned and reactive psychological influences and
      psychosocial constructs as predictors of riding with drinking drivers (RWDD) in a
      sample of individuals aged 18 to 21. METHODS: College students (N = 508)
      completed web-based questionnaires assessing RWDD, psychosocial constructs
      (attitudes, expectancies, and norms), and reasoned and reactive influences
      (intentions and willingness) at baseline (the middle of the spring semester) and
      again 1 and 6 months later. Regression was used to analyze reasoned and reactive
      influences as proximal predictors of RWDD at the 6-month follow-up. Subsequent
      analyses examined the relationship between the psychosocial constructs as distal
      predictors of RWDD and the mediation effects of reasoned and reactive influences.
      RESULTS: Both reasoned and reactive influences predicted RWDD, while only the
      reactive influence had a significant unique effect. Reactive influences
      significantly mediated the effects of peer norms, attitudes, and drinking
      influences on RWDD. Nearly all effects were constant across gender except
      parental norms (significant for females). CONCLUSIONS: Findings highlight that
      the important precursors of RWDD were reactive influences, attitudes, and peer
      and parent norms. These findings suggest several intervention methods,
      specifically normative feedback interventions, parent-based interventions, and
      brief motivational interviewing, may be particularly beneficial in reducing RWDD.

PMID- 25939373
TI  - F8 gene: embedded in a region of genomic instability representing a hotspot of
      complex rearrangements.

PMID- 25939374
TI  - Does fetal growth restriction lead to increased brain injury as detected by
      neonatal cranial ultrasound in premature infants?
AB  - AIM: Intra-uterine growth restriction (IUGR) is an important cause for
      prematurity as well as a significant risk factor for neurodevelopmental deficits.
      In this study, we aimed to examine the association between IUGR and early brain
      injury on neonatal cranial ultrasound in preterm infants. METHODS: This
      retrospective cohort study examined the relationship between IUGR and neonatal
      cranial ultrasound findings in preterm infants <32 weeks gestation with IUGR,
      compared with gestation and year of birth-matched appropriately grown infants, in
      a tertiary level neonatal unit. Primary outcome was incidence and severity of
      intraventricular haemorrhage (IVH), periventricular leucomalacia (PVL) and
      hydrocephalus detected by cranial ultrasound in the neonatal period. RESULTS: A
      total of 153 IUGR and 306 non-IUGR preterm infants <32 weeks were included. The
      rates of IVH (21.6% vs. 23.9%), severe IVH (3.9% vs. 4.6%), PVL (8.4% vs. 9.4%),
      cystic PVL (2.6% vs. 0%) and hydrocephalus (0.7% vs. 0.3%) were similar in the
      two groups. Composite outcome of death and severe brain injury (severe IVH,
      cystic PVL and hydrocephalus) was greater (20.2% vs. 9.1%, P = 0.001) in IUGR
      infants. CONCLUSION: IUGR did not lead to increased neonatal brain injury on
      cranial ultrasound but was associated with increased mortality. Advanced neonatal
      neuroimaging techniques may be necessary to estimate risk and to provide
      prognostic information of adverse neurological outcomes in this vulnerable
      population.

PMID- 25939375
TI  - Subcutaneous immunization with a novel immunogenic candidate (urease) confers
      protection against Brucella abortus and Brucella melitensis infections.
AB  - Brucellosis is a world prevalent endemic illness that is transmitted from
      domestic animals to humans. Brucella spp. exploits urease for survival in the
      harsh conditions of stomach during the gastrointestinal infection. In this study,
      we examined the immune response and the protection elicited by using recombinant
      Brucella urease (rUrease) vaccination in BALB/c mice. The urease gene was cloned
      in pET28a and the resulting recombinant protein was employed as subunit vaccine.
      Recombinant protein was administered subcutaneously and intraperitoneally. Dosage
      reduction was observed with subcutaneous (SC) vaccination when compared with
      intraperitoneal (IP) vaccination. rUrease induced mixed Th1-Th2 immune responses
      with high titers of specific IgG1 and IgG2a. In lymphocyte proliferation assay,
      splenocytes from IP and SC-vaccinated mice displayed a strong recall
      proliferative response with high amounts of IL-4, IL-12 and IFN-gamma production.
      Vaccinated mice were challenged with virulent Brucella melitensis, B. abortus and
      B. suis. The SC vaccination route exhibited a higher degree of protection than IP
      vaccination (p value <= 0.05). Altogether, our results indicated that rUrease
      could be a useful antigen candidate for the development of subunit vaccines
      against brucellosis. 

PMID- 25939376
TI  - Yeast cell wall and live yeast products and their combination in broiler diets
      formulated with weekly ingredient variations.
AB  - A 6-week broiler study was conducted to evaluate whether subjecting the
      intestinal microflora of broilers to the effect of weekly variations in feed
      ingredients could be ameliorated by the inclusion of yeast-derived feed
      additives: a yeast cell wall extract (YCW), live yeast culture (LY) or their
      combination (YCW + LY). Recent changes in ingredient prices have motivated
      producers to formulate diets not necessarily based primarily on corn and soya
      bean meal. Intestinal microflora in birds can vary significantly based on the
      ingredient composition of their diet, and the make-up of the flora can influence
      overall bird performance. Within the three nutrient phases of this study, birds
      were fed either a traditional corn-soya ingredient profile or a variable
      ingredient regimen, which had weekly changes in the ingredient composition. There
      were consistent ameliorative effects of the yeast treatments in both the corn
      soya and the variable-ingredient groups throughout all 6 weeks, with the YCW + LY
      combination showing a reduced effect when compared to either product fed alone.
      The effectiveness of YCW and LY on ameliorating the effects of weekly ingredient
      variations appeared most effective during the starter and grower phases, but was
      less significant during the sixth week. 

PMID- 25939378
TI  - Life course models for upper aero-digestive tract cancer.
AB  - Upper aero-digestive tract (UADT) cancers are collectively cancers of various
      human body sites, such as the oral cavity, pharynx, oesophagus and larynx.
      Worldwide, they are the fourth most frequent cancer type and the fourth most
      common cause of mortality from cancer. Many studies have shown that several
      chronic diseases, such as cancer, which occur more commonly in later adulthood,
      are influenced by social and psychological circumstances during birth, childhood,
      adolescence and early adult life. It is suggested that the build up of
      problematic circumstances throughout life is the cause of disease, rather than
      circumstances that happen at one point in time. UADT cancer is a chronic disease
      of complex multifactorial origin and most of the underlying exposures/risks
      cannot be considered as individual factors or in isolation, as they act at
      different levels, which differ from time to time. Thus, life-course epidemiology,
      rather than drawing false dichotomies between different risk factors of the
      underlying disease, attempts to integrate biological and social risk processes
      that cause the chronic disease. It studies how socially patterned exposures
      during all stages of life--childhood, adolescence and early adult--influence
      disease risk in adulthood and socio-economic position and hence may account for
      social inequalities in adult health and mortality. Furthermore, varying health
      effects, according to the timing or duration of exposure to socio-economic
      circumstances, may indicate important traces to the causes of cancer. In this
      paper, we have attempted to draw a conceptual framework on the relationships
      between socio-economic inequalities, oral health risk factors along the life
      course of an individual and incidence of UADT cancer.

PMID- 25939377
TI  - Progressive inflammation-mediated neurodegeneration after traumatic brain or
      spinal cord injury.
AB  - Traumatic brain injury (TBI) has been linked to dementia and chronic
      neurodegeneration. Described initially in boxers and currently recognized across
      high contact sports, the association between repeated concussion (mild TBI) and
      progressive neuropsychiatric abnormalities has recently received widespread
      attention, and has been termed chronic traumatic encephalopathy. Less well
      appreciated are cognitive changes associated with neurodegeneration in the brain
      after isolated spinal cord injury. Also under-recognized is the role of sustained
      neuroinflammation after brain or spinal cord trauma, even though this
      relationship has been known since the 1950s and is supported by more recent
      preclinical and clinical studies. These pathological mechanisms, manifested by
      extensive microglial and astroglial activation and appropriately termed chronic
      traumatic brain inflammation or chronic traumatic inflammatory encephalopathy,
      may be among the most important causes of post-traumatic neurodegeneration in
      terms of prevalence. Importantly, emerging experimental work demonstrates that
      persistent neuroinflammation can cause progressive neurodegeneration that may be
      treatable even weeks after traumatic injury.

PMID- 25939379
TI  - Indirect interactions among tropical tree species through shared rodent seed
      predators: a novel mechanism of tree species coexistence.
AB  - The coexistence of numerous tree species in tropical forests is commonly
      explained by negative dependence of recruitment on the conspecific seed and tree
      density due to specialist natural enemies that attack seeds and seedlings
      ('Janzen-Connell' effects). Less known is whether guilds of shared seed predators
      can induce a negative dependence of recruitment on the density of different
      species of the same plant functional group. We studied 54 plots in tropical
      forest on Barro Colorado Island, Panama, with contrasting mature tree densities
      of three coexisting large seeded tree species with shared seed predators. Levels
      of seed predation were far better explained by incorporating seed densities of
      all three focal species than by conspecific seed density alone. Both positive and
      negative density dependencies were observed for different species combinations.
      Thus, indirect interactions via shared seed predators can either promote or
      reduce the coexistence of different plant functional groups in tropical forest. 

PMID- 25939381
TI  - Tip110 Regulates the Cross Talk between p53 and Hypoxia-Inducible Factor 1alpha
      under Hypoxia and Promotes Survival of Cancer Cells.
AB  - Hypoxia often occurs under various physiological and pathophysiological
      conditions, including solid tumors; it is linked to malignant transformation,
      metastatic progression, and treatment failure or resistance. Tip110 protein plays
      important roles in several known physiological and pathophysiological processes,
      including cancers. Thus, in the present study we investigated the regulation of
      Tip110 expression under hypoxia. Hypoxia led to Tip110 protein degradation
      through the ubiquitin-proteasome system. Under hypoxia, Tip110 stabilized p53,
      which in return destabilized Tip110. In addition, Tip110 regulated hypoxia
      inducible factor 1alpha (HIF-1alpha), likely through enhancement of its protein
      stability. Furthermore, Tip110 upregulated p300, a known coactivator for both p53
      and HIF-1alpha. Expression of a p53(22/23) mutant deficient in p300 binding
      accelerated Tip110 degradation under hypoxia. Tip110 knockdown resulted in the
      inhibition of cell proliferation and cell death in the presence of p53. Finally,
      significantly less Tip110, p53, and HIF-1alpha was detected in the hypoxic region
      of bone metastasis tumors in a mouse model of human melanoma cells. Taken
      together, these results suggest Tip110 is an important mediator in the cross talk
      between p53 and HIF-1alpha in response to hypoxic stress. 

PMID- 25939382
TI  - RBM45 Modulates the Antioxidant Response in Amyotrophic Lateral Sclerosis through
      Interactions with KEAP1.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease
      characterized by the selective loss of motor neurons. Various factors contribute
      to the disease, including RNA binding protein dysregulation and oxidative stress,
      but their exact role in pathogenic mechanisms remains unclear. We have recently
      linked another RNA binding protein, RBM45, to ALS via increased levels of protein
      in the cerebrospinal fluid of ALS patients and its localization to cytoplasmic
      inclusions in ALS motor neurons. Here we show RBM45 nuclear exit in ALS spinal
      cord motor neurons compared to controls, a phenotype recapitulated in vitro in
      motor neurons treated with oxidative stressors. We find that RBM45 binds and
      stabilizes KEAP1, the inhibitor of the antioxidant response transcription factor
      NRF2. ALS lumbar spinal cord lysates similarly show increased cytoplasmic binding
      of KEAP1 and RBM45. Binding of RBM45 to KEAP1 impedes the protective antioxidant
      response, thus contributing to oxidative stress-induced cellular toxicity. Our
      findings thus describe a novel link between a mislocalized RNA binding protein
      implicated in ALS (RBM45) and dysregulation of the neuroprotective antioxidant
      response seen in the disease.

PMID- 25939384
TI  - SOCS3 Drives Proteasomal Degradation of TBK1 and Negatively Regulates Antiviral
      Innate Immunity.
AB  - TANK-binding kinase 1 (TBK1)-mediated induction of type I interferon (IFN) plays
      a critical role in host antiviral responses and immune homeostasis. The negative
      regulation of TBK1 activity is largely unknown. We report that suppressor of
      cytokine signaling 3 (SOCS3) inhibits the IFN-beta signaling pathway by promoting
      proteasomal degradation of TBK1. Overexpression and knockdown experiments
      indicated that SOCS3 is a negative regulator of IFN regulatory factor 3 (IRF3)
      phosphorylation and IFN-beta transcription. Moreover, SOCS3 directly associates
      with TBK1, and they colocalize in the cytoplasm. SOCS3 catalyzes K48-linked
      polyubiquitination of TBK1 at Lys341 and Lys344 and promotes subsequent TBK1
      degradation. On the contrary, SOCS3 knockdown markedly increases the abundance of
      TBK1. Interestingly, both the BOX domain of SOCS3 and Ser172 phosphorylation of
      TBK1 are indispensable for the processes of ubiquitination and degradation.
      Ectopic expression of SOCS3 significantly inhibits vesicular stomatitis virus
      (VSV) and influenza A virus strain A/WSN/33 (WSN)-induced IRF3 phosphorylation
      and facilitates the replication of WSN virus by detecting the transcription of
      its viral RNA (vRNA). Knockdown of SOCS3 represses WSN replication. Collectively,
      these results demonstrate that SOCS3 acts as a negative regulator of IFN-beta
      signal by ubiquitinating and degrading TBK1, shed light on the understanding of
      antiviral innate immunity, and provide a potential target for developing
      antiviral agents.

PMID- 25939383
TI  - Disruption of Wnt/beta-Catenin Signaling and Telomeric Shortening Are
      Inextricable Consequences of Tankyrase Inhibition in Human Cells.
AB  - Maintenance of chromosomal ends (telomeres) directly contributes to cancer cell
      immortalization. The telomere protection enzymes belonging to the tankyrase
      (Tnks) subfamily of poly(ADP-ribose) polymerases (PARPs) have recently been shown
      to also control transcriptional response to secreted Wnt signaling molecules.
      Whereas Tnks inhibitors are currently being developed as therapeutic agents for
      targeting Wnt-related cancers and as modulators of Wnt signaling in tissue
      engineering agendas, their impact on telomere length maintenance remains unclear.
      Here, we leveraged a collection of Wnt pathway inhibitors with previously
      unassigned mechanisms of action to identify novel pharmacophores supporting Tnks
      inhibition. A multifaceted experimental approach that included structural,
      biochemical, and cell biological analyses revealed two distinct chemotypes with
      selectivity for Tnks enzymes. Using these reagents, we revealed that Tnks
      inhibition rapidly induces DNA damage at telomeres and telomeric shortening upon
      long-term chemical exposure in cultured cells. On the other hand, inhibitors of
      the Wnt acyltransferase Porcupine (Porcn) elicited neither effect. Thus, Tnks
      inhibitors impact telomere length maintenance independently of their affects on
      Wnt/beta-catenin signaling. We discuss the implications of these findings for
      anticancer and regenerative medicine agendas dependent upon chemical inhibitors
      of Wnt/beta-catenin signaling.

PMID- 25939380
TI  - Association between trends in clinical variables and outcome in intensive care
      patients with faecal peritonitis: analysis of the GenOSept cohort.
AB  - INTRODUCTION: Patients admitted to intensive care following surgery for faecal
      peritonitis present particular challenges in terms of clinical management and
      risk assessment. Collaborating surgical and intensive care teams need shared
      perspectives on prognosis. We aimed to determine the relationship between dynamic
      assessment of trends in selected variables and outcomes. METHODS: We analysed
      trends in physiological and laboratory variables during the first week of
      intensive care unit (ICU) stay in 977 patients at 102 centres across 16 European
      countries. The primary outcome was 6-month mortality. Secondary endpoints were
      ICU, hospital and 28-day mortality. For each trend, Cox proportional hazards (PH)
      regression analyses, adjusted for age and sex, were performed for each endpoint.
      RESULTS: Trends over the first 7 days of the ICU stay independently associated
      with 6-month mortality were worsening thrombocytopaenia (mortality: hazard ratio
      (HR) = 1.02; 95% confidence interval (CI), 1.01 to 1.03; P < 0.001) and renal
      function (total daily urine output: HR =1.02; 95% CI, 1.01 to 1.03; P < 0.001;
      Sequential Organ Failure Assessment (SOFA) renal subscore: HR = 0.87; 95% CI,
      0.75 to 0.99; P = 0.047), maximum bilirubin level (HR = 0.99; 95% CI, 0.99 to
      0.99; P = 0.02) and Glasgow Coma Scale (GCS) SOFA subscore (HR = 0.81; 95% CI,
      0.68 to 0.98; P = 0.028). Changes in renal function (total daily urine output and
      renal component of the SOFA score), GCS component of the SOFA score, total SOFA
      score and worsening thrombocytopaenia were also independently associated with
      secondary outcomes (ICU, hospital and 28-day mortality). We detected the same
      pattern when we analysed trends on days 2, 3 and 5. Dynamic trends in all other
      measured laboratory and physiological variables, and in radiological findings,
      changes in respiratory support, renal replacement therapy and inotrope and/or
      vasopressor requirements failed to be retained as independently associated with
      outcome in multivariate analysis. CONCLUSIONS: Only deterioration in renal
      function, thrombocytopaenia and SOFA score over the first 2, 3, 5 and 7 days of
      the ICU stay were consistently associated with mortality at all endpoints. These
      findings may help to inform clinical decision making in patients with this common
      cause of critical illness.

PMID- 25939385
TI  - Drosophila DBT Autophosphorylation of Its C-Terminal Domain Antagonized by SPAG
      and Involved in UV-Induced Apoptosis.
AB  - Drosophila DBT and vertebrate CKIepsilon/delta phosphorylate the period protein
      (PER) to produce circadian rhythms. While the C termini of these orthologs are
      not conserved in amino acid sequence, they inhibit activity and become
      autophosphorylated in the fly and vertebrate kinases. Here, sites of C-terminal
      autophosphorylation were identified by mass spectrometry and analysis of DBT
      truncations. Mutation of 6 serines and threonines in the C terminus (DBT(C/ala))
      prevented autophosphorylation-dependent DBT turnover and electrophoretic mobility
      shifts in S2 cells. Unlike the effect of autophosphorylation on CKIdelta, DBT
      autophosphorylation in S2 cells did not reduce its in vitro activity. Moreover,
      overexpression of DBT(C/ala) did not affect circadian behavior differently from
      wild-type DBT (DBT(WT)), and neither exhibited daily electrophoretic mobility
      shifts, suggesting that DBT autophosphorylation is not required for clock
      function. While DBT(WT) protected S2 cells and larvae from UV-induced apoptosis
      and was phosphorylated and degraded by the proteasome, DBT(C/ala) did not protect
      and was not degraded. Finally, we show that the HSP-90 cochaperone spaghetti
      protein (SPAG) antagonizes DBT autophosphorylation in S2 cells. These results
      suggest that DBT autophosphorylation regulates cell death and suggest a potential
      mechanism by which the circadian clock might affect apoptosis.

PMID- 25939387
TI  - Two New Brackish Ciliates, Amphileptus spiculatus sp. n. and A. bellus sp. n.
      from Mangrove Wetlands in Southern China, with Notes on the Molecular Phylogeny
      of the Family Amphileptidae (Protozoa, Ciliophora, Pleurostomatida).
AB  - Two new brackish pleurostomatid ciliates, Amphileptus spiculatus sp. n. and A.
      bellus sp. n. were collected from mangrove wetlands of southern China and their
      morphology and molecular phylogeny were studied. Amphileptus spiculatus sp. n.
      can be distinguished from congeners by the presence of 11-14 right and 6-8 left
      kineties, two macronuclear nodules and a conspicuous beak-like anterior body end.
      Amphileptus bellus sp. n. is characterized by the presence of 2-4 macronuclear
      nodules, 31-35 right and 6 or 7 left kineties and two types of extrusomes.
      Phylogenetic analyses based on SSU rDNA sequences data indicate that the family
      Amphileptidae is paraphyletic. 

PMID- 25939388
TI  - A density functional theory insight towards the rational design of ionic liquids
      for SO2 capture.
AB  - A systematic density functional theory (DFT) analysis has been carried out to
      obtain information at the molecular level on the key parameters related to
      efficient SO2 capture by ionic liquids (ILs). A set of 55 ILs, for which high gas
      solubility is expected, has been selected. SO2 solubility of ILs was firstly
      predicted based on the COSMO-RS (Conductor-like Screening Model for Real
      Solvents) method, which provides a good prediction of gas solubility data in ILs
      without prior experimental knowledge of the compounds' features. Then,
      interactions between SO2 and ILs were deeply analyzed through DFT simulations.
      This work provides valuable information about required factors at the molecular
      level to provide high SO2 solubility in ILs, which is crucial for further
      implementation of these materials in the future. In our opinion, systematic
      research on ILs for SO2 capture increases our knowledge about those factors which
      could be controlled at the molecular level, providing an approach for the
      rational design of task-specific ILs. 

PMID- 25939386
TI  - Overexpression of the Insulin-Like Growth Factor II Receptor Increases beta
      Amyloid Production and Affects Cell Viability.
AB  - Amyloid beta (Abeta) peptides originating from amyloid precursor protein (APP) in
      the endosomal-lysosomal compartments play a critical role in the development of
      Alzheimer's disease (AD), the most common type of senile dementia affecting the
      elderly. Since insulin-like growth factor II (IGF-II) receptors facilitate the
      delivery of nascent lysosomal enzymes from the trans-Golgi network to endosomes,
      we evaluated their role in APP metabolism and cell viability using mouse
      fibroblast MS cells deficient in the murine IGF-II receptor and corresponding
      MS9II cells overexpressing the human IGF-II receptors. Our results show that IGF
      II receptor overexpression increases the protein levels of APP. This is
      accompanied by an increase of beta-site APP-cleaving enzyme 1 levels and an
      increase of beta- and gamma-secretase enzyme activities, leading to enhanced
      Abeta production. At the cellular level, IGF-II receptor overexpression causes
      localization of APP in perinuclear tubular structures, an increase of lipid raft
      components, and increased lipid raft partitioning of APP. Finally, MS9II cells
      are more susceptible to staurosporine-induced cytotoxicity, which can be
      attenuated by beta-secretase inhibitor. Together, these results highlight the
      potential contribution of IGF-II receptor to AD pathology not only by regulating
      expression/processing of APP but also by its role in cellular vulnerability. 

PMID- 25939390
TI  - Highly sensitive detection for proteins using graphene oxide-aptamer based
      sensors.
AB  - In recent years, the detection of proteins by using bare graphene oxide (GO) to
      quench the fluorescence of fluorescein-labeled aptamers has been reported.
      However, the proteins can be adsorbed on the surface of bare GO to prevent the
      sensitivity from further being improved. In order to solve this problem,
      polyethylene glycol (PEG)-protected GO was used to prevent the proteins using
      thrombin as an example from nonspecific binding. The detection limit was improved
      compared to bare GO under the optimized ratio of GO to PEG concentration. The
      results show that our method is a promising technique for the detection of
      proteins. 

PMID- 25939389
TI  - A distinct role for interleukin-6 as a major mediator of cellular adjustment to
      an altered culture condition.
AB  - Tissue microenvironment adjusts biological properties of different cells by
      modulating signaling pathways and cell to cell interactions. This study showed
      that epithelial-mesenchymal transition (EMT)/ mesenchymal-epithelial transition
      (MET) can be modulated by altering culture conditions. HPV E6/E7-transfected
      immortalized oral keratinocytes (IHOK) cultured in different media displayed
      reversible EMT/MET accompanied by changes in cell phenotype, proliferation, gene
      expression at transcriptional, and translational level, and migratory and
      invasive activities. Cholera toxin, a major supplement to culture medium, was
      responsible for inducing the morphological and biological changes of IHOK.
      Cholera toxin per se induced EMT by triggering the secretion of interleukin 6 (IL
      6) from IHOK. We found IL-6 to be a central molecule that modulates the
      reversibility of EMT based not only on the mRNA level but also on the level of
      secretion. Taken together, our results demonstrate that IL-6, a cytokine whose
      transcription is activated by alterations in culture conditions, is a key
      molecule for regulating reversible EMT/MET. This study will contribute to
      understand one way of cellular adjustment for surviving in unfamiliar conditions.

PMID- 25939391
TI  - Redox inactive metal ion triggered N-dealkylation by an iron catalyst with
      dioxygen activation: a lesson from lipoxygenases.
AB  - Utilization of dioxygen as the terminal oxidant at ambient temperature is always
      a challenge in redox chemistry, because it is hard to oxidize a stable redox
      metal ion like iron(III) to its high oxidation state to initialize the catalytic
      cycle. Inspired by the dioxygenation and co-oxidase activity of lipoxygenases,
      herein, we introduce an alternative protocol to activate the sluggish iron(III)
      species with non-redox metal ions, which can promote its oxidizing power to
      facilitate substrate oxidation with dioxygen, thus initializing the catalytic
      cycle. In oxidations of N,N-dimethylaniline and its analogues, adding Zn(OTf)2 to
      the [Fe(TPA)Cl2]Cl catalyst can trigger the amine oxidation with dioxygen,
      whereas [Fe(TPA)Cl2]Cl alone is very sluggish. In stoichiometric oxidations, it
      has also been confirmed that the presence of Zn(OTf)2 can apparently improve the
      electron transfer capability of the [Fe(TPA)Cl2]Cl complex. Experiments using
      different types of substrates as trapping reagents disclosed that the iron(IV)
      species does not occur in the catalytic cycle, suggesting that oxidation of
      amines is initialized by electron transfer rather than hydrogen abstraction.
      Combined experiments from UV-Vis, high resolution mass spectrometry,
      electrochemistry, EPR and oxidation kinetics support that the improved electron
      transfer ability of iron(III) species originates from its interaction with added
      Lewis acids like Zn(2+) through a plausible chloride or OTf(-) bridge, which has
      promoted the redox potential of iron(III) species. The amine oxidation mechanism
      was also discussed based on the available data, which resembles the co-oxidase
      activity of lipoxygenases in oxidative dealkylation of xenobiotic metabolisms
      where an external electron donor is not essential for dioxygen activation.

PMID- 25939392
TI  - Registered report: Discovery and preclinical validation of drug indications using
      compendia of public gene expression data.
AB  - The Science Translational Medicine in 2011 (Sirota et al., 2011). The key
      experiments being replicated include Figure 4C and D and Supplemental Figure 1.
      In these figures, Sirota and colleagues. tested a proof of concept experiment
      validating their prediction that cimetidine, a histamine-2 (H2) receptor agonist
      commonly used to treat peptic ulcers (Kubecova et al., 2011), would be effective
      against lung adenocarcinoma (Figure 4C and D). As a control they also tested the
      effects of cimetidine against renal carcinoma, for which it was not predicted to
      be efficacious (Supplemental Figure 1). The Reproducibility Project: Cancer
      Biology is a collaboration between the eLife. 

PMID- 25939394
TI  - Recovery rate of children with moderate acute malnutrition treated with ready-to
      use supplementary food (RUSF) or improved corn-soya blend (CSB+): a randomized
      controlled trial.
AB  - OBJECTIVE: To compare an improved corn-soya blend (CSB+) with a ready-to-use
      supplementary food (RUSF) to test the hypothesis that satisfactory recovery rate
      will be achieved with CSB+ or RUSF when these foods provide 50 % of the child's
      energy requirement, the 50 % remaining coming from usual diet. DESIGN: A
      comparative efficacy trial study was conducted with moderately wasted children,
      using a controlled randomized design, with parallel assignment for RUSF or CSB+.
      Every child received a daily ration of 167 kJ (40 kcal)/kg body weight during 56
      d with a follow-up performed every 14 d. Every caregiver received nutrition
      counselling at enrolment and at each follow-up visit. SETTING: Health districts
      of Mvog-Beti and Evodoula in the Centre region of Cameroon. SUBJECTS: Eight
      hundred and thirty-three children aged 6-59 months were screened and eighty-one
      malnourished children (weight-for-height Z-score between -3 and -2) aged 25-59
      months were selected. RESULTS: Of children treated with CSB+ and RUSF, 73 % (95 %
      CI 59 %, 87 %) and 85 % (95 % CI 73 %, 97 %), respectively, recovered from
      moderate acute malnutrition, with no significant difference between groups. The
      mean duration of treatment required to achieve recovery was 44 d in the RUSF
      group and 51 d in the CSB+ group (log-rank test, P=0.0048). CONCLUSIONS: There
      was no significant difference in recovery rate between the groups. Both CSB+ and
      RUSF were relatively successful for the treatment of moderate acute malnutrition
      in children. Despite the relatively low ration size provided, the recovery rates
      observed for both groups were comparable to or higher than those reported in
      previous studies, a probable effect of nutrition education.

PMID- 25939393
TI  - A multicenter study shows PTEN deletion is strongly associated with seminal
      vesicle involvement and extracapsular extension in localized prostate cancer.
AB  - BACKGROUND: Loss of the phosphatase and tensin homolog (PTEN) tumor suppressor
      gene is a promising marker of aggressive prostate cancer. Active surveillance and
      watchful waiting are increasingly recommended to patients with small tumors felt
      to be low risk, highlighting the difficulties of Gleason scoring in this setting.
      There is an urgent need for predictive biomarkers that can be rapidly deployed to
      aid in clinical decision-making. Our objectives were to assess the incidence and
      ability of PTEN alterations to predict aggressive disease in a multicenter study.
      METHODS: We used recently developed probes optimized for sensitivity and
      specificity in a four-color FISH deletion assay to study the Canary Retrospective
      multicenter Prostate Cancer Tissue Microarray (TMA). This TMA was constructed
      specifically for biomarker validation from radical prostatectomy specimens, and
      is accompanied by detailed clinical information with long-term follow-up.
      RESULTS: In 612 prostate cancers, the overall rate of PTEN deletion was 112
      (18.3%). Hemizygous PTEN losses were present in 55/612 (9.0%) of cancers, whereas
      homozygous PTEN deletion was observed in 57/612 (9.3%) of tumors. Significant
      associations were found between PTEN status and pathologic stage (P < 0.0001),
      seminal vesicle invasion (P = 0.0008), extracapsular extension (P < 0.0001), and
      Gleason score (P = 0.0002). In logistic regression analysis of clinical and
      pathological variables, PTEN deletion was significantly associated with
      extracapsular extension, seminal vesicle involvement, and higher Gleason score.
      In the 406 patients in which clinical information was available, PTEN homozygous
      (P = 0.009) deletion was associated with worse post-operative recurrence-free
      survival (number of events = 189), pre-operative prostate specific antigen (PSA)
      (P < 0.001), and pathologic stage (P = 0.03). CONCLUSION: PTEN status assessed by
      FISH is an independent predictor for recurrence-free survival in multivariate
      models, as were seminal vesicle invasion, extracapsular extension, and Gleason
      score, and preoperative PSA. Furthermore, these data demonstrate that the assay
      can be readily introduced at first diagnosis in a cost effective manner analogous
      to the use of FISH for analysis of HER2/neu status in breast cancer. Combined
      with published research beginning 17 years ago, both the data and tools now exist
      to implement a PTEN assay in the clinic.

PMID- 25939395
TI  - Preclinical Pharmacokinetics and Pharmacodynamics and Content Analysis of Gnetol
      in Foodstuffs.
AB  - Studies were undertaken to evaluate the bioavailability in rats and content
      analysis of gnetol in Gnetum gnemon products reported to contain gnetol and to
      examine the pharmacological properties of gnetol in in vitro models including
      anti-inflammatory/analgesic, antidiabetic, anti-adipogenesis, and anticancer
      activity. Male Sprague-Dawley rats were cannulated and dosed either intravenously
      with gnetol (10 mg/kg) or orally (100 mg/kg). Various methanolic extractions of
      G. gnemon products were quantified. Gnetol's effect on cell viability in selected
      cell lines with or without inflammatory stimulus was assessed. alpha-Amylase and
      alpha-glucosidase inhibition was evaluated. Cyclooxygenase (COX)-1, COX-2, and
      histone deacetylase inhibition and adipogenesis inhibition were examined. After
      oral and intravenous administration, gnetol was detected in both serum and urine
      as the parent compound and as a glucuronidated metabolite. The bioavailability of
      gnetol was determined to be 6%. Gnetol is rapidly glucuronidated and is excreted
      in urine and via nonrenal routes. Gnetol was found to exist as an aglycone and as
      a glycoside in G. gnemon products. Gnetol showed concentration-dependent
      reductions in cell viability in cancer cell lines with greatest activity in
      colorectal cancer and potent COX-1, histone deacetylase, and weak COX-2
      activities along with limited reduction in inflammation. Gnetol also possessed
      concentration-dependent alpha-amylase, alpha-glucosidase, and adipogenesis
      activities. Pretreatment of mice with gnetol was able to increase the latency
      period to response in analgesia models.

PMID- 25939396
TI  - Beyond the usual suspects: a multidimensional genetic exploration of infant
      attachment disorganization and security.
AB  - Although the environmental influences on infant attachment disorganization and
      security are well-studied, little is known about their heritability. Candidate
      gene studies have shown small, often non-replicable effects. In this study, we
      gathered the largest sample (N = 657) of ethnically homogenous, 14-month-old
      children with both observed attachment and genome-wide data. First, we used a
      Genome-Wide Association Study (GWAS) approach to identify single nucleotide
      polymorphisms (SNPs) associated with attachment disorganization and security.
      Second, we annotated them into genes (Versatile Gene-based Association Study) and
      functional pathways. Our analyses provide evidence of novel genes (HDAC1, ZNF675,
      BSCD1) and pathways (synaptic transmission, cation transport) associated with
      attachment disorganization. Similar analyses identified a novel gene (BECN1) but
      no distinct pathways associated with attachment security. The results of this
      first extensive, exploratory study on the molecular-genetic basis of infant
      attachment await replication in large, independent samples.

PMID- 25939397
TI  - Ecological impacts of large-scale disposal of mining waste in the deep sea.
AB  - Deep-Sea Tailings Placement (DSTP) from terrestrial mines is one of several large
      scale industrial activities now taking place in the deep sea. The scale and
      persistence of its impacts on seabed biota are unknown. We sampled around the
      Lihir and Misima island mines in Papua New Guinea to measure the impacts of
      ongoing DSTP and assess the state of benthic infaunal communities after its
      conclusion. At Lihir, where DSTP has operated continuously since 1996, abundance
      of sediment infauna was substantially reduced across the sampled depth range (800
      2020 m), accompanied by changes in higher-taxon community structure, in
      comparison with unimpacted reference stations. At Misima, where DSTP took place
      for 15 years, ending in 2004, effects on community composition persisted 3.5
      years after its conclusion. Active tailings deposition has severe impacts on deep
      sea infaunal communities and these impacts are detectable at a coarse level of
      taxonomic resolution. 

PMID- 25939398
TI  - Using Small Molecules to Prepare Vesicles with Designable Shapes and Sizes via
      Frame-Guided Assembly Strategy.
AB  - Following the principle of frame-guided assembly (FGA), a small amphiphilic
      molecule, sodium dodecyl sulfate, is shown to form vesicles with cholesterol as
      the leading hydrophobic group. These findings not only demonstrate the generality
      of the FGA but also provide a clue to understand the formation mechanism of the
      cell membrane, and even the origin of life. 

PMID- 25939399
TI  - Positive effects of early androgen therapy on the behavioral phenotype of boys
      with 47,XXY.
AB  - 47, XXY occurs in up to 1 in 650 male births and is associated with androgen
      deficiency, neurodevelopmental delays, and atypical social-behaviors. Previously,
      we showed that young boys with 47, XXY who received early hormonal therapy (EHT)
      had significantly improved neurodevelopment. The objective of this follow-up
      study was to examine the effects of EHT on social behavior in boys with 47, XXY.
      The study consisted of boys prenatally diagnosed with 47, XXY who were referred
      for evaluations. Twenty-nine boys received three injections of 25 mg testosterone
      enanthate and 57 controls did not receive EHT. Behavioral functioning was
      assessed using the Behavior Rating Inventory of Executive Function, Social
      Responsiveness Scale, 2nd Ed., and the Child Behavior Checklist for Ages 6-18.
      The hypothesis that EHT may affect behavior was formulated prior to data
      collection. Questionnaire data was prospectively obtained and analyzed to test
      for significance between two groups. Significant differences were identified
      between group's scores over time in Social Communication (P=0.007), Social
      Cognition (P=0.006), and Total T-score (P=0.001) on the SRS-2; Initiation
      (P=0.05) on the BRIEF; and Externalizing Problems (P=0.024), Affective Problems
      (P=0.05), and Aggressive Behaviors (P=0.031) on the CBCL. This is the third study
      revealing positive effects of EHT on boys with XXY. There was a significant
      improvements associated with the 47, XXY genotype in boys who received EHT.
      Research is underway on the neurobiological mechanisms, and later developmental
      effects of EHT.

PMID- 25939400
TI  - Slow magnetic relaxation in two-dimensional 3d-4f complexes based on phenyl
      pyrimidyl substituted nitronyl nitroxide radicals.
AB  - Three isostructural two-dimensional 2p-3d-4f complexes, namely,
      {Tb(hfac)3[Cu(hfac)2]3(NITPhPyrim)2}.2CH2Cl2 and 1
      {Ln(hfac)3[Cu(hfac)2]3(NITPhPyrim)2} (Ln(III) = Ho 2, Yb 3; hfac =
      hexafluoroacetylacetonate; NITPhPyrim = 2-[4-(5-pyrimidyl)phenyl]-4,4,5,5
      tetramethylimidazoline-1-oxyl-3-oxide), were characterized in terms of structure
      and magnetism. These heterospin compounds possess a two-dimensional sheet
      structure involving Cu(II) and Ln(III) ions bridged by NITPhPyrim radicals
      through their NO groups and pyrimidine rings. DC magnetic studies show that these
      complexes exhibit ferromagnetic exchange coupling between radical ligands and
      metal atoms. AC measurements of the Tb complex reveal slow relaxation of the
      magnetization. Interestingly, the Tb complex displays two field-induced
      relaxation processes.

PMID- 25939401
TI  - Scan-stratified case-control sampling for modeling blood-brain barrier integrity
      in multiple sclerosis.
AB  - Multiple sclerosis (MS) is an immune-mediated neurological disease that causes
      morbidity and disability. In patients with MS, the accumulation of lesions in the
      white matter of the brain is associated with disease progression and worse
      clinical outcomes. Breakdown of the blood-brain barrier in newer lesions is
      indicative of more active disease-related processes and is a primary outcome
      considered in clinical trials of treatments for MS. Such abnormalities in active
      MS lesions are evaluated in vivo using contrast-enhanced structural MRI, during
      which patients receive an intravenous infusion of a costly magnetic contrast
      agent. In some instances, the contrast agents can have toxic effects. Recently,
      local image regression techniques have been shown to have modest performance for
      assessing the integrity of the blood-brain barrier based on imaging without
      contrast agents. These models have centered on the problem of cross-sectional
      classification in which patients are imaged at a single study visit and pre
      contrast images are used to predict post-contrast imaging. In this paper, we
      extend these methods to incorporate historical imaging information, and we find
      the proposed model to exhibit improved performance. We further develop scan
      stratified case-control sampling techniques that reduce the computational burden
      of local image regression models, while respecting the low proportion of the
      brain that exhibits abnormal vascular permeability.

PMID- 25939403
TI  - Genes with de novo mutations are shared by four neuropsychiatric disorders
      discovered from NPdenovo database.

PMID- 25939402
TI  - Small molecules demonstrate the role of dynamin as a bi-directional regulator of
      the exocytosis fusion pore and vesicle release.
AB  - Hormones and neurotransmitters are stored in specialised vesicles and released
      from excitable cells through exocytosis. During vesicle fusion with the plasma
      membrane, a transient fusion pore is created that enables transmitter release.
      The protein dynamin is known to regulate fusion pore expansion (FPE). The
      mechanism is unknown, but requires its oligomerisation-stimulated GTPase
      activity. We used a palette of small molecule dynamin modulators to reveal bi
      directional regulation of FPE by dynamin and vesicle release in chromaffin cells.
      The dynamin inhibitors Dynole 34-2 and Dyngo 4a and the dynamin activator Ryngo 1
      23 reduced or increased catecholamine released from single vesicles,
      respectively. Total internal reflection fluorescence (TIRF) microscopy
      demonstrated that dynamin stimulation with Ryngo 1-23 reduced the number of
      neuropeptide Y (NPY) kiss-and-run events, but not full fusion events, and slowed
      full fusion release kinetics. Amperometric stand-alone foot signals, representing
      transient kiss-and-run events, were less frequent but were of longer duration,
      similarly to full amperometric spikes and pre-spike foot signals. These effects
      are not due to alterations in vesicle size. Ryngo 1-23 action was blocked by
      inhibitors of actin polymerisation or myosin II. Therefore, we demonstrate using
      a novel pharmacological approach that dynamin not only controls FPE during
      exocytosis, but is a bi-directional modulator of the fusion pore that increases
      or decreases the amount released from a vesicle during exocytosis if it is
      activated or inhibited, respectively. As such, dynamin has the ability to
      exquisitely fine-tune transmitter release. 

PMID- 25939404
TI  - Integrated carboxylic carbon nanotube pathways with membranes for voltage
      activated humidity detection and microclimate regulation.
AB  - This work describes some single walled carboxylic carbon nanotubes with
      outstanding transport properties when assembled in a 3D microarray working like a
      humidity membrane-sensor and an adjustable moisture regulator. Combined nano
      assembly approaches are used to build up a better quality pathway through which
      assisted-charge and mass transport synchronically takes place. The structure
      electrical response relationship is found, while controllable and tunable donor
      acceptor interactions established at material interfaces are regarded as key
      factors for the accomplishment of charge transportation, enhanced electrical
      responses and adjustable moisture exchange. Raman and infrared spectroscopy
      provides indications about the fine structural and chemical features of the
      hybrid-composite membranes, resulting in perfect agreement with related
      morphology and electrical properties. Enhanced and modular electrical response to
      changes in the surrounding atmosphere is concerned with doping events, while
      assisted moisture regulation is discussed in relation to swelling and hopping
      actions. The electro-activated hybrid-composite membrane proposed in this work
      can be regarded as an attractive 'sense-to-act' precursor for smart long-distance
      monitoring systems with capability to adapt itself and provide local comfortable
      microenvironments. 

PMID- 25939405
TI  - Cocrystal Formation through Mechanochemistry: from Neat and Liquid-Assisted
      Grinding to Polymer-Assisted Grinding.
AB  - Mechanochemistry is an effective method for the preparation of multicomponent
      crystal systems. In the present work, we propose an alternative to the
      established liquid-assisted grinding (LAG) approach. Polymer-assisted grinding
      (POLAG) is demonstrated to provide a new class of catalysts for improving
      reaction rate and increasing product diversity during mechanochemical
      cocrystallization reactions. We demonstrate that POLAG provides advantages
      comparable to the conventional liquid-assisted process, whilst eliminating the
      risk of unwanted solvate formation as well as enabling control of resulting
      particle size. It represents a new approach for the development of functional
      materials through mechanochemistry, and possibly opens new routes toward the
      understanding of the mechanisms and pathways of mechanochemical cocrystal
      formation. 

PMID- 25939406
TI  - Association of Physical Fitness With Pain in Women With Fibromyalgia: The al
      Andalus Project.
AB  - OBJECTIVE: This population-based cross-sectional study aimed to characterize the
      association of different components of physical fitness with pain levels, pain
      related catastrophizing, and chronic pain self-efficacy in women with
      fibromyalgia (FM). METHODS: A total of 468 women with FM participated. The
      experience of pain was assessed with different tools (algometry, a numeric rating
      scale [revised FM impact questionnaire], a visual analog scale, and the bodily
      pain subscale on the Short Form 36 health survey). We also assessed pain-related
      catastrophizing and chronic pain self-efficacy. Physical fitness was assessed
      with performance-based tests (Senior Fitness Test battery and handgrip
      dynamometry). A standardized composite score was computed for each component of
      physical fitness (aerobic fitness, muscle strength, flexibility, and motor
      agility), and their average comprised a clustered global fitness profile.
      RESULTS: Overall, higher physical fitness was consistently associated with lower
      levels of pain, lower pain-related catastrophizing, and higher chronic pain self
      efficacy (regardless of the pain assessment method and the fitness test
      evaluated). Muscle strength and flexibility were independently associated with
      pain (P < 0.005 for both), and participants with high muscle strength plus high
      flexibility (combined effect) had the lowest levels of pain in this population.
      Aerobic fitness and flexibility were independently associated with pain-related
      catastrophizing (P < 0.001 for both) and chronic pain self-efficacy (P < 0.001
      for both), and participants with high flexibility plus high aerobic fitness
      (combined effect) had the best catastrophizing and self-efficacy profiles.
      CONCLUSION: Our results suggest that higher physical fitness is associated with
      lower levels of pain, lower pain-related catastrophizing, and higher chronic pain
      self-efficacy in women with FM. These results might have implications for future
      intervention studies in this population.

PMID- 25939407
TI  - Bioinspired Carbon/SnO2 Composite Anodes Prepared from a Photonic Hierarchical
      Structure for Lithium Batteries.
AB  - A carbon/SnO2 composite (C-SnO2) with hierarchical photonic structure was
      fabricated from the templates of butterfly wings. We have investigated for the
      first time its application as the anode material for lithium-ion batteries. It
      was demonstrated to have high reversible capacities, good cycling stability, and
      excellent high-rate discharge performance, as shown by a capacitance of ~572 mAh
      g(-1) after 100 cycles, 4.18 times that of commercial SnO2 powder (137 mAh g(
      1)); a far better recovery capability of 94.3% was observed after a step-increase
      and sudden-recovery current. An obvious synergistic effect was found between the
      porous, hierarchically photonic microstructure and the presence of carbon; the
      synergy guarantees an effective flow of electrolyte and a short diffusion length
      of lithium ions, provides considerable buffering room, and prevents aggregation
      of SnO2 particles in the discharge/charge processes. This nature-inspired
      strategy points out a new direction for the fabrication of alternative anode
      materials. 

PMID- 25939408
TI  - Impaired postural stability after laparoscopic surgery.
AB  - BACKGROUND: Early postoperative mobilisation may reduce patient morbidity and
      improve hospital efficiency by accelerated discharge. The aim of this study was
      to measure postural stability early after laparoscopic surgery in order to assess
      how early it is safe to mobilise and discharge patients. METHODS: We included 25
      women undergoing outpatient gynaecological laparoscopic surgery in the study.
      Patients received standardised anaesthesia with propofol, remifentanil and
      rocuronium. Postural stability was assessed preoperatively, at 30 min after
      tracheal extubation, and at discharge from the post-anaesthesia care unit using a
      force platform where sway area, mean sway and sway velocity were determined. The
      assessments were done with eyes closed and with eyes open. The primary outcome
      was the change in sway area with eyes closed 30 min after extubation. Data are
      reported as median (25-75% range). RESULTS: Three patients could not perform all
      the test's 30 min after extubation. Thirty minutes after extubation, sway area
      with eyes closed had increased significantly with 84 mm(2) (9-172, P = 0.011) and
      108 mm(2) with eyes open (25-295, P = 0.0017). Median mean sway had also
      increased significantly 30 min postoperatively. No significant changes were found
      for sway velocity. We found no significant changes in mean sway, sway area or
      sway velocity at discharge from the post-anaesthesia care unit approximately 2 h
      after surgery. CONCLUSION: Postural stability was significantly impaired 30 min
      after outpatient gynaecological laparoscopic surgery. However, the postural
      stability was normalised at discharge from the post-anaesthesia care unit 2 h
      after surgery.

PMID- 25939409
TI  - Response to comments on "diagnosis and management of osteoporosis of the jaw: a
      systematic review and international consensus".

PMID- 25939410
TI  - Inhibitors of melanogenesis: a patent review (2009 - 2014).
AB  - INTRODUCTION: Melanogenesis is the process of producing the melanin pigment, in
      which a series of chemical and enzymatic pathways are involved. Modulation at any
      level of this process would become an important approach in the treatment of
      hyper- or hypopigmentation-related diseases. Since hyperpigmentation covers
      important issue in cosmetics, there is a need of such review to understand and
      update this field to the public domain. AREAS COVERED: In this review, authors
      discuss most recent melanogenesis inhibitors published in the patents since 2009.
      The up-to-date overview of classical catechol-based tyrosinase inhibitors to non
      classical melanogenesis inhibitors with different mechanism of action is
      discussed. Inhibitors including small-interfering RNA and peptides from ~ 30
      patents and their associated literature are also discussed. EXPERT OPINION:
      Although a huge number of melanogenesis inhibitors have been reported, the future
      studies should be focused towards the identification of new inhibitors with a
      clear mechanism. The next breakthrough in the field therefore, is likely to come
      from the detailed structure-activity relationship studies of thioureas with
      improved therapeutic profiles. Targeting other parameters such as number or size
      of melanosomes, maturation of melanosomes and expression of melanogenic enzymes
      may give the best results to overcome toxicity and other formulation problems.

PMID- 25939411
TI  - Treatment of Ventilator-Associated Pneumonia Using Intravenous Colistin Alone or
      in Combination with Inhaled Colistin in Critically Ill Children.
AB  - OBJECTIVE: The objective of this study was to compare the safety and efficacy of
      inhaled plus intravenous (IV) colistin with that of IV colistin alone in
      critically ill children with ventilator-associated pneumonia (VAP) due to
      colistin-only susceptible (COS) Gram-negative bacteria (GNB). STUDY DESIGN AND
      PATIENTS: This retrospective cohort study included critically ill children aged 1
      month to 18 years with culture-documented monomicrobial VAP due to COS GNB.
      RESULTS: Fifty patients were included, and 32 patients received IV colistin
      alone, whereas 18 patients received inhaled plus IV colistin. No between-cohort
      differences were observed in clinical (p = 0.49) and microbiological outcomes (p
      = 0.68), or VAP-related mortality (p = 0.99). Although the bacterial eradication
      rates did not differ in either treatment group, the median time to bacterial
      eradication (TBE) was significantly shorter in the inhaled plus IV colistin group
      than in the IV colistin group. The additional use of inhaled colistin was the
      only independent factor associated with TBE, and it shortened the median TBE by 3
      days. Only one patient in the IV colistin group developed reversible
      nephrotoxicity. Mild bronchoconstriction was observed in three patients at the
      time of administration of the first doses of inhaled colistin, which did not
      require discontinuation of treatment. CONCLUSIONS: The present study has
      demonstrated that the addition of inhaled colistin to IV colistin led to a
      shorter TBE in critically ill children with VAP due to COS GNB. However, it did
      not lead to a significant difference in the clinical and microbiological outcomes
      of VAP.

PMID- 25939412
TI  - Investigation of association between hip osteoarthritis susceptibility loci and
      radiographic proximal femur shape.
AB  - OBJECTIVE: To test whether previously reported hip morphology or osteoarthritis
      (OA) susceptibility loci are associated with proximal femur shape as represented
      by statistical shape model (SSM) modes and as univariate or multivariate
      quantitative traits. METHODS: We used pelvic radiographs and genotype data from
      929 subjects with unilateral hip OA who had been recruited previously for the
      Arthritis Research UK Osteoarthritis Genetics Consortium genome-wide association
      study. We built 3 SSMs capturing the shape variation of the OA-unaffected
      proximal femur in the entire mixed-sex cohort and for male/female-stratified
      cohorts. We selected 41 candidate single-nucleotide polymorphisms (SNPs)
      previously reported as being associated with hip morphology (for replication
      analysis) or OA (for discovery analysis) and for which genotype data were
      available. We performed 2 types of analysis for genotype-phenotype associations
      between these SNPs and the modes of the SSMs: 1) a univariate analysis using
      individual SSM modes and 2) a multivariate analysis using combinations of SSM
      modes. RESULTS: The univariate analysis identified association between rs4836732
      (within the ASTN2 gene) and mode 5 of the female SSM (P = 0.0016) and between
      rs6976 (within the GLT8D1 gene) and mode 7 of the mixed-sex SSM (P = 0.0003). The
      multivariate analysis identified association between rs5009270 (near the IFRD1
      gene) and a combination of modes 3, 4, and 9 of the mixed-sex SSM (P = 0.0004).
      Evidence of associations remained significant following adjustment for multiple
      testing. All 3 SNPs had previously been associated with hip OA. CONCLUSION: These
      de novo findings suggest that rs4836732, rs6976, and rs5009270 may contribute to
      hip OA susceptibility by altering proximal femur shape.

PMID- 25939413
TI  - Acute psychosis in an adolescent with undiagnosed homocystinuria.
AB  - Homocystinuria due to cystathionine-beta-synthase deficiency (CBS deficiency)
      usually presents with ectopia lentis, myopia, intellectual disability, skeletal
      anomalies resembling Marfan syndrome, and thromboembolic events. Whereas
      neurodevelopment impairments have been often described in untreated
      homocystinuria adult patients, acute psychosis has rarely been reported as a
      presenting symptom of the disease. Here, we describe a 17-year-old girl affected
      by CBS deficiency presenting acute onset of visual hallucinations, behavioral
      perseverance, psychomotor hyperactivity, and affective inappropriateness. Ectopia
      lentis, diagnosed several years before, didn't have been considered as possible
      sign of a metabolic disorder. Psychotic symptoms were unresponsive to the
      conventional antipsychotic drugs and relieved after pyridoxine and folic acid
      treatment. CONCLUSION: A diagnosis of homocystinuria due to CBS deficiency should
      be considered in patients presenting, as target signs, ectopia lentis with or
      without learning difficulties, and should also be taken into account as a
      potentially treatable cause of acute psychosis in childhood and adolescence. WHAT
      IS KNOWN: * Homocystinuria frequently present with ectopia lentis, myopia,
      cognitive impairment, Marfan-like phenotype, osteoporosis, cerebrovascular, or
      cardiac thrombosis. * Acute psychosis has rarely been reported as a presenting
      symptom of the disease. WHAT IS NEW: * The complete psychotic symptoms' remission
      with pharmacological doses of pyridoxine and folic acid, without antipsychotic
      drugs.

PMID- 25939414
TI  - Mitral annular peak systolic velocity in pediatric patients with ectopic atrial
      tachycardia.

PMID- 25939415
TI  - Adrenaline in cardiac arrest: Prefilled syringes are faster.
AB  - OBJECTIVE: Standard ampoules and prefilled syringes of adrenaline are widely
      available in Australasian EDs for use in cardiac arrest. We hypothesise that
      prefilled syringes can be administered more rapidly and accurately when compared
      with the two available standard ampoules. METHODS: This is a triple arm
      superiority study comparing the time to i.v. administration and accuracy of
      dosing of three currently available preparations of adrenaline. RESULTS: In their
      standard packaging, prefilled syringes were on average more than 12 s faster to
      administer than the 1 mL 1:1000 ampoules and more than 16 s faster than the 10 mL
      1:10,000 ampoules (P < 0.01 in both comparisons). With packaging removed, the
      time to administration was equal for the 1 mL (1:1000) ampoule and the prefilled
      syringe. Accuracy of dosing was excellent with both the 10 mL (1:10 000) ampoules
      and prefilled syringes. The 1 mL (1:1000) ampoules delivered a small number of
      markedly inaccurate doses, but these did not reach statistical significance.
      CONCLUSIONS: The speed of administration of adrenaline utilising a Minijet (CSL
      Limited, Parkville, Victoria, Australia) is faster than using adrenaline in glass
      ampoules presented in their plastic packaging. Removing the plastic packaging
      from the 1 mL (1 mg) ampoule might result in more rapid administration similar to
      the Minijet. Resuscitation personnel requiring rapid access to adrenaline should
      consider storing it as either Minijets or ampoules devoid of packaging. These
      results might be extrapolatable to other clinical scenarios, including pre
      hospital and anaesthesia, where other drugs are required for rapid use.

PMID- 25939416
TI  - Connective tissue diseases: Is SLE many single-organ diseases or an overlapping
      spectrum?

PMID- 25939417
TI  - Pharmacotherapy: Going upstream: peptidomimetics block shared-epitope signalling.

PMID- 25939418
TI  - Clinical trials: A transparent future for clinical trial reporting.

PMID- 25939419
TI  - Inflammation: Soluble MRP8/14 recruits neutrophils via TLR4.

PMID- 25939420
TI  - Experimental arthritis: Fullerene nanoparticles ameliorate disease in arthritis
      mouse model.

PMID- 25939421
TI  - The direct integral method for confidence intervals for the ratio of two location
      parameters.
AB  - In a relative risk analysis of colorectal caner on nutrition intake scores across
      genders, we show that, surprisingly, when comparing the relative risks for men
      and women based on the index of a weighted sum of various nutrition scores, the
      problem reduces to forming a confidence interval for the ratio of two
      (asymptotically) normal random variables. The latter is an old problem, with a
      substantial literature. However, our simulation results suggest that existing
      methods often either give inaccurate coverage probabilities or have a positive
      probability to produce confidence intervals with infinite length. Motivated by
      such a problem, we develop a new methodology which we call the Direct Integral
      Method for Ratios (DIMER), which, unlike the other methods, is based directly on
      the distribution of the ratio. In simulations, we compare this method to many
      others. These simulations show that, generally, DIMER more closely achieves the
      nominal confidence level, and in those cases that the other methods achieve the
      nominal levels, DIMER has comparable confidence interval lengths. The methodology
      is then applied to a real data set, and with follow up simulations. 

PMID- 25939422
TI  - Hairy Polyp of the Nasopharynx Arising from the Eustachian Tube.
AB  - Hairy polyps of the nasopharynx display characteristic radiological imaging
      findings, including the presence of fat in the polypoid mass. Furthermore,
      diagnostic imaging is useful for delineating the site of origin of these lesions,
      which can facilitate surgical planning. For instance hairy polyps that arise from
      the right Eustachian tube can be amputated via a trans-nasal approach with
      endoscopy, but may necessitate a two stage approach in order to avoid injury to
      critical structures, such as the internal carotid artery. On histology, hairy
      polyps comprise an outer keratinizing squamous epithelium with adnexal tissue,
      including hair follicles, and central fibroadipose and cartilaginous tissue.
      These features are exemplified in this sine qua non radiology-pathology
      correlation article. 

PMID- 25939423
TI  - Precise Three-Dimensional Scan-Free Multiple-Particle Tracking over Large Axial
      Ranges with Tetrapod Point Spread Functions.
AB  - We employ a novel framework for information-optimal microscopy to design a family
      of point spread functions (PSFs), the Tetrapod PSFs, which enable high-precision
      localization of nanoscale emitters in three dimensions over customizable axial
      (z) ranges of up to 20 MUm with a high numerical aperture objective lens. To
      illustrate, we perform flow profiling in a microfluidic channel and show scan
      free tracking of single quantum-dot-labeled phospholipid molecules on the surface
      of living, thick mammalian cells. 

PMID- 25939424
TI  - Structural and Functional Impact of Parkinson Disease-Associated Mutations in the
      E3 Ubiquitin Ligase Parkin.
AB  - Mutations in the PARKIN/PARK2 gene that result in loss-of-function of the
      encoded, neuroprotective E3 ubiquitin ligase Parkin cause recessive, familial
      early-onset Parkinson disease. As an increasing number of rare Parkin sequence
      variants with unclear pathogenicity are identified, structure-function analyses
      will be critical to determine their disease relevance. Depending on the specific
      amino acids affected, several distinct pathomechanisms can result in loss of
      Parkin function. These include disruption of overall Parkin folding, decreased
      solubility, and protein aggregation. However pathogenic effects can also result
      from misregulation of Parkin autoinhibition and of its enzymatic functions. In
      addition, interference of binding to coenzymes, substrates, and adaptor proteins
      can affect its catalytic activity too. Herein, we have performed a comprehensive
      structural and functional analysis of 21 PARK2 missense mutations distributed
      across the individual protein domains. Using this combined approach, we were able
      to pinpoint some of the pathogenic mechanisms of individual sequence variants.
      Similar analyses will be critical in gaining a complete understanding of the
      complex regulations and enzymatic functions of Parkin. These studies will not
      only highlight the important residues, but will also help to develop novel
      therapeutics aimed at activating and preserving an active, neuroprotective form
      of Parkin. 

PMID- 25939425
TI  - Inhibition of hedgehog signalling attenuates UVB-induced skin photoageing.
AB  - The hedgehog (Hh) signalling pathway regulates normal development and cell
      proliferation in metazoan organisms, but its aberrant activation can promote
      tumorigenesis and progression of a variety of aggressive human cancers including
      skin cancer. Despite its importance, little is known about its role in
      photoageing, a type of UV-induced skin lesions. In this study, we investigated
      the involvement of Hh signalling in the photoageing process as well as the use of
      an Hh-regulating alkaloid compound as a novel therapeutic drug to regulate
      photoageing in keratinocytes. We found that UVB induced Hh signalling by the
      expression of Hh ligands and Hh-mediated transcription factors, respectively.
      Moreover, UVB-induced Hh activation relied on mitogen-activated protein kinase
      (p38, ERK and JNK) activity and inflammatory responses (upregulation of COX-2, IL
      1beta, IL-6 and TNF-alpha), resulting in premature senescence and photoageing in
      vitro and in vivo. Notably, a selected Hh inhibitor, evodiamine, mediated
      photoageing blockade in a mouse skin model. Taken together, our findings
      demonstrated that Hh signalling is associated with UVB-induced photoageing, while
      pharmacological inhibition of Hh signalling significantly reduced experimental
      photoageing, indicating its potential for use as a therapeutic target for this
      disease.

PMID- 25939426
TI  - Identification of sulforhodamine B photodegradation products present in
      nonpermanent tattoos by micro liquid chromatography coupled with tandem high
      resolution mass spectrometry.
AB  - This article deals with the photodegradation of sulforhodamine B, a dye widely
      used in nonpermanent tattoos. Degradation evidence was obtained from both aqueous
      and sweat-simulating solutions of the dye after 9 days of Solarbox irradiation.
      The identification of the degradation products was achieved using a nontarget
      approach. For this purpose, a micro liquid chromatography method coupled with
      tandem high-resolution mass spectrometry was developed. In addition, the chemical
      structures of five degradation products and two dye impurities were elucidated.
      The degradation products were the same for both types of solution, whereas the
      degradation rate of the dye in sweat-simulating solution was slightly faster than
      that in aqueous solution. The method was also applied to samples of tattooed
      pigskin subjected to irradiation, in order to better simulate the irradiation
      effects on the dye used on the skin. None of the degradation products found in
      the sulforhodamine B solutions were identified in the degraded tattooed pigskin
      samples, but a new signal at m/z 637.3051 (positive ionization) was found, and
      the structure of the corresponding molecule was elucidated. The mutagenicity of
      the photodegradation products was evaluated using a quantitative structure
      activity relationship approach, which gave negative results for all the
      structures elucidated. Graphical Abstract Comparison between tattoed pigskin
      before and after photodegration process. Strategies for the identification of
      sulforhodamine B degradation products.

PMID- 25939428
TI  - Post-explant visualization of thrombi in outflow grafts and their junction to a
      continuous-flow total artificial heart using a high-definition miniaturized
      camera.
AB  - Post-explant evaluation of the continuous-flow total artificial heart in
      preclinical studies can be extremely challenging because of the device's unique
      architecture. Determining the exact location of tissue regeneration, neointima
      formation, and thrombus is particularly important. In this report, we describe
      our first successful experience with visualizing the Cleveland Clinic continuous
      flow total artificial heart using a custom-made high-definition miniature camera.

PMID- 25939427
TI  - Naringin Improves Neuronal Insulin Signaling, Brain Mitochondrial Function, and
      Cognitive Function in High-Fat Diet-Induced Obese Mice.
AB  - The epidemic and experimental studies have confirmed that the obesity induced by
      high-fat diet not only caused neuronal insulin resistance, but also induced brain
      mitochondrial dysfunction as well as learning impairment in mice. Naringin has
      been reported to posses biological functions which are beneficial to human
      cognitions, but its protective effects on HFD-induced cognitive deficits and
      underlying mechanisms have not been well characterized. In the present study Male
      C57BL/6 J mice were fed either a control or high-fat diet for 20 weeks and then
      randomized into four groups treated with their respective diets including control
      diet, control diet + naringin, high-fat diet (HFD), and high-fat diet + naringin
      (HFDN). The behavioral performance was assessed by using novel object recognition
      test and Morris water maze test. Hippocampal mitochondrial parameters were
      analyzed. Then the protein levels of insulin signaling pathway and the AMP
      activated protein kinase (AMPK) in the hippocampus were detected by Western blot
      method. Our results showed that oral administration of naringin significantly
      improved the learning and memory abilities as evidenced by increasing recognition
      index by 52.5% in the novel object recognition test and inducing a 1.05-fold
      increase in the crossing-target number in the probe test, and ameliorated
      mitochondrial dysfunction in mice caused by HFD consumption. Moreover, naringin
      significantly enhanced insulin signaling pathway as indicated by a 34.5% increase
      in the expression levels of IRS-1, a 47.8% decrease in the p-IRS-1, a 1.43-fold
      increase in the p-Akt, and a 1.89-fold increase in the p-GSK-3beta in the
      hippocampus of the HFDN mice versus HFD mice. Furthermore, the AMPK activity
      significantly increased in the naringin-treated (100 mg kg(-1) d(-1)) group.
      These findings suggest that an enhancement in insulin signaling and a decrease in
      mitochondrial dysfunction through the activation of AMPK may be one of the
      mechanisms that naringin improves cognitive functions in HFD-induced obese mice.

PMID- 25939429
TI  - GXD: a community resource of mouse Gene Expression Data.
AB  - The Gene Expression Database (GXD) is an extensive, easily searchable, and freely
      available database of mouse gene expression information
      (www.informatics.jax.org/expression.shtml). GXD was developed to foster progress
      toward understanding the molecular basis of human development and disease. GXD
      contains information about when and where genes are expressed in different
      tissues in the mouse, especially during the embryonic period. GXD collects
      different types of expression data from wild-type and mutant mice, including RNA
      in situ hybridization, immunohistochemistry, RT-PCR, and northern and western
      blot results. The GXD curators read the scientific literature and enter the
      expression data from those papers into the database. GXD also acquires expression
      data directly from researchers, including groups doing large-scale expression
      studies. GXD currently contains nearly 1.5 million expression results for over
      13,900 genes. In addition, it has over 265,000 images of expression data,
      allowing users to retrieve the primary data and interpret it themselves. By being
      an integral part of the larger Mouse Genome Informatics (MGI) resource, GXD's
      expression data are combined with other genetic, functional, phenotypic, and
      disease-oriented data. This allows GXD to provide tools for researchers to
      evaluate expression data in the larger context, search by a wide variety of
      biologically and biomedically relevant parameters, and discover new data
      connections to help in the design of new experiments. Thus, GXD can provide
      researchers with critical insights into the functions of genes and the molecular
      mechanisms of development, differentiation, and disease.

PMID- 25939430
TI  - Genipin crosslinking of cartilage enhances resistance to biochemical degradation
      and mechanical wear.
AB  - Collagen crosslinking enhances many beneficial properties of articular cartilage,
      including resistance to chemical degradation and mechanical wear, but many
      crosslinking agents are cytotoxic. The purpose of this study was to evaluate the
      effectiveness of genipin, a crosslinking agent with favorable biocompatibility
      and cytotoxicity, as a potential treatment to prevent the degradation and wear of
      articular cartilage. First, the impact of genipin concentration and treatment
      duration on the viscoelastic properties of bovine articular cartilage was
      quantified. Next, two short-term (15 min) genipin crosslinking treatments were
      chosen, and the change in collagenase digestion, cartilage wear, and the friction
      coefficient of the tissue with these treatments was measured. Finally,
      chondrocyte viability after exposure to these genipin treatments was assessed.
      Genipin treatment increased the stiffness of healthy, intact cartilage in a dose
      dependent manner. The 15-min crosslinking treatments improved cartilage's
      resistance to both chemical degradation, particularly at the articular surface,
      and to damage due to mechanical wear. These enhancements were achieved without
      sacrificing the low coefficient of friction of the tissue and at a genipin dose
      that preserved chondrocyte viability. The results of this study suggest that
      collagen crosslinking via genipin may be a promising preventative treatment to
      slow the degradation of cartilage.

PMID- 25939431
TI  - Towards pain-free diagnosis of skin diseases through multiplexed microneedles:
      biomarker extraction and detection using a highly sensitive blotting method.
AB  - Immunodiagnostic microneedles provide a novel way to extract protein biomarkers
      from the skin in a minimally invasive manner for analysis in vitro. The
      technology could overcome challenges in biomarker analysis specifically in solid
      tissue, which currently often involves invasive biopsies. This study describes
      the development of a multiplex immunodiagnostic device incorporating mechanisms
      to detect multiple antigens simultaneously, as well as internal assay controls
      for result validation. A novel detection method is also proposed. It enables
      signal detection specifically at microneedle tips and therefore may aid the
      construction of depth profiles of skin biomarkers. The detection method can be
      coupled with computerised densitometry for signal quantitation. The antigen
      specificity, sensitivity and functional stability of the device were assessed
      against a number of model biomarkers. Detection and analysis of endogenous
      antigens (interleukins 1alpha and 6) from the skin using the device was
      demonstrated. The results were verified using conventional enzyme-linked
      immunosorbent assays. The detection limit of the microneedle device, at <=10
      pg/mL, was at least comparable to conventional plate-based solid-phase enzyme
      immunoassays. 

PMID- 25939432
TI  - Enhanced epidermal localization of topically applied steroids using SPACETM
      peptide.
AB  - The balance of efficacy and safety of topical corticosteroids (TCs) depends on
      their ability to penetrate into and be retained within the skin. Here, we
      evaluated the ability of SPACETM peptide to enhance epidermal delivery and
      localization of three model TCs. In vitro and in vivo skin penetration studies
      were performed to evaluate penetration of TCs into and across the skin in the
      presence of various formulations of SPACETM peptide. Topical formulations of
      corticosterone containing free SPACETM peptide produced significantly enhanced
      epidermal penetration and localization. Ratio of drug deposition in the skin and
      receiver (efficacy/safety, indicative of ratio of local to systemic uptake)
      exhibited higher values for SPACETM peptide-based formulation as compared to
      aqueous and hydroethanolic solutions and CortizoneTM cream. Mass spectrometry
      analysis showed that SPACETM peptide associates with corticosterone, which may
      explain its enhanced retention effect. SPACETM peptide also enhanced dermal
      retention of two more TCs (hydrocortisone and triamcinolone acetonide) compared
      to the vehicle control. An in vivo study in mice further established the ability
      of SPACETM peptide to enhance skin retention of hydrocortisone without producing
      elevated blood concentrations. These results show that SPACETM peptide is an
      effective additive to the formulation for enhanced skin localization of topical
      steroids. 

PMID- 25939433
TI  - How to rapidly construct a spatial-numerical representation in preliterate
      children (at least temporarily).
AB  - Spatial processing of numbers has emerged as one of the basic properties of
      humans' mathematical thinking. However, how and when number-space relations
      develop is a highly contested issue. One dominant view has been that a link
      between numbers and left/right spatial directions is constructed based on
      directional experience associated with reading and writing. However, some early
      forms of a number-space link have been observed in preschool children who cannot
      yet read and write. As literacy experience is evidently not necessary for number
      space effects, we are searching for other potential sources of this association.
      Here we propose and test a hypothesis that the number-space link can be quickly
      constructed in preschool children's cognition on the basis of spatially oriented
      visuo-motor activities. We trained 3- and 4-year-old children with a non
      numerical spatial movement task (left-to-right or right-to-left), where via touch
      screen children had to move a frog across a pond. After the training, children
      had to perform a numerosity comparison task. After left-to-right training, we
      observed a SNARC-like effect (reactions to smaller numbers were faster on the
      left side, and reactions to larger numbers on the right side), and after right-to
      left training a reverse effect. These results are the first to show a causal link
      between visuo-motor activities and number-space associations in children before
      they learn to read and write. We argue that simple activities, such as manual
      games, dominant in a given society, might shape number-space associations in
      children in a way similar to lifelong reading training. 

PMID- 25939434
TI  - Left ventricular pseudoaneurysm after mitral valve replacement: Review of
      pseudoaneurysms late after mitral valve replacement.
AB  - Left ventricular pseudoaneurysm (LVPA) due to incomplete or late rupture after
      mitral valve replacement is a rare condition but can be life threatening if it
      develops into perdicardial tamponade. LVPA may develop de novo after the surgical
      procedure or may be a sequela of an earlier rupture. Clinical presentation
      includes shortness of breath, heart failure, chest pain, endocarditis, and
      pericardial tamponade. However, it can also have an asymptomatic course. The
      recommended treatment for LVPA is surgical repair. Conservative follow-up is an
      alternative for patients who refuse surgical treatment or are considered high
      risk for re-operation. We conducted a review of all the available literature on
      cases of LVPA after mitral valve replacement and present the findings here. 

PMID- 25939435
TI  - Prevalence of atrial fibrillation and the HATCH score: Intensified monitoring of
      patients with high HATCH score.
AB  - AIM: The HATCH score [hypertension, age > 75 years, previous transient ischemic
      attack (TIA) or stroke (doubled), chronic obstructive pulmonary disease, heart
      failure (doubled)] has been established to identify patients who are at risk of
      developing persistent forms of AF. We investigated whether this score is
      associated with the prevalence of AF in order to guide diagnostic efforts and
      therapy. PATIENTS AND METHODS: The data of 150,408 consecutive patients who were
      hospitalized at the University Hospital of Rostock between 2007 and 2012 were
      analyzed. Factors constituting the HATCH score and the presence of AF were
      prospectively documented using ICD-10 admission codes. RESULTS: Patients were
      67.6 +/- 13.6 years of age with a mean HATCH score of 1.48 +/- 1.02; 16 % had a
      history of AF and 4 % suffered a TIA or stroke. The prevalence of AF increased
      significantly with the HATCH score up to 60.0 % (p < 0.001). In all, 63 % of the
      patients had a HATCH score of 0 and 1 without any history of stroke. CONCLUSION:
      The HATCH score correlates with the occurrence of AF, since the prevalence of AF
      rises with rising score values. Therefore, the HATCH score may be used to select
      patients for intensified ECG monitoring. Moreover, the score may also be used for
      stroke risk assessment, as none of the patients with a low HATCH score suffered a
      stroke.

PMID- 25939436
TI  - Recent-onset dilated cardiomyopathy associated with Borrelia burgdorferi
      infection.
AB  - BACKGROUND: Several recent small studies have suggested a causal link between
      Lyme disease and dilated cardiomyopathy (DCM) by demonstrating the presence of
      the Borrelia burgdorferi (Bb) genome in the myocardium of patients with recent
      onset DCM. The aim of this study was to further investigate the effect of
      targeted antibiotic treatment of Bb-related recent-onset DCM in a larger cohort
      of patients. PATIENTS AND METHODS: We performed endomyocardial biopsy (EMB) in
      110 individuals (53 +/- 11 years, 34 women) with recent-onset unexplained DCM,
      and detected the Bb genome in 22 (20 %) subjects. Bb-positive patients were
      subsequently treated with intravenous ceftriaxone for 21 days in addition to
      conventional heart failure medication. RESULTS: At the 1-year follow-up, a
      significant improvement in left ventricular (LV) ejection fraction (26 +/- 6  vs.
      44 +/- 12 %; p < 0.01) and a decrease in LV end-diastolic (69 +/- 7 vs. 63 +/- 11
      mm; p < 0.01) and end-systolic (61 +/- 9 vs. 52 +/- 4 mm; p < 0.01) diameters
      were documented. Moreover, a significant improvement in heart failure symptoms
      (NYHA class 3.4 +/- 0.6 vs. 1.5 +/- 0.7; p < 0.01) was also observed. CONCLUSION:
      Targeted antibiotic treatment of Bb-related recent-onset DCM in addition to
      conventional heart failure therapy is associated with favorable cardiac
      remodeling and improvement of heart failure symptoms.

PMID- 25939437
TI  - Neuromuscular comorbidity, heart failure, and atrial fibrillation as prognostic
      factors in left ventricular hypertrabeculation/noncompaction.
AB  - BACKGROUND: There is some controversy concerning the prognosis of patients with
      left ventricular hypertrabeculation/noncompaction (LVHT). LVHT is frequently
      associated with neuromuscular disorders (NMDs). The aim of this study was to
      assess cardiac and neurological findings as predictors of mortality in patients
      with LVHT. PATIENTS AND METHODS: The study included patients with LVHT diagnosed
      between June 1995 and January 2014 in one echocardiographic laboratory. They
      underwent a baseline cardiologic examination and were invited for a neurological
      examination. Between January and February 2014, their survival status was
      assessed. RESULTS: LVHT was diagnosed in 220 patients (68 female, aged 52 +/- 17
      years) with a prevalence of 0.35 %/year. During a follow-up of 72 +/- 61 months,
      65 patients died. The mortality was 5 %/year. A neurological investigation was
      performed on 173 patients (79 %) and revealed specific NMDs in 31 (14 %), NMD of
      unknown etiology in 103 (47 %), and normal findings in 39 (18 %) patients. In
      multivariate analysis, the predictors of mortality were increased age (p =
      0.0001), presence of a specific NMD (p = 0.0062) or NMD of unknown etiology (p =
      0.0062), heart failure NYHA III (p = 0.0396), atrial fibrillation (p = 0.0022),
      and sinus tachycardia (p = 0.0395). CONCLUSIONS: LVHT patients should undergo
      systematic neurological examinations. Whether an optimal therapy of heart failure
      and atrial fibrillation will improve the prognosis of LVHT patients needs to be
      addressed in further studies.

PMID- 25939438
TI  - Relationship between serum visfatin levels and coronary slow-flow phenomenon.
AB  - BACKGROUND: Increased levels of visfatin, a novel adipocytokine, are reported in
      atherosclerosis, obesity, and type 2 diabetes. The aim of the present study was
      to investigate the relationship between coronary slow flow (CSF) and visfatin in
      patients undergoing elective coronary angiography for suspected coronary artery
      disease. PATIENTS AND METHODS: A total of 140 recruited participants (90 patients
      with CSF and 50 controls) were divided into two groups according to their
      coronary flow rates. Coronary flow was quantified by thrombolysis in myocardial
      infarction (TIMI) frame count (TFC). RESULTS: Serum visfatin levels were higher
      in the CSF group than in the control group (3.29 +/- 1.11 vs. 2.70 +/- 1.08
      ng/ml, p = 0.003). A significant correlation was found between TFC and visfatin
      (r = 0.535, p < 0.001). The area under the receiver operating characteristic
      curve was 0.720 (95 % confidence interval, 0.622-0.817, p < 0.001) for visfatin
      in the diagnosis of CSF. If a cut-off value of 2.59 ng/ml was used, higher levels
      of visfatin could predict the presence of CSF with 78.9 % sensitivity and 64.0 %
      specificity. CONCLUSION: Visfatin levels might be a useful biomarker for
      predicting CSF in patients undergoing diagnostic coronary angiography.

PMID- 25939439
TI  - MiR-137 inhibits proliferation and angiogenesis of human glioblastoma cells by
      targeting EZH2.
AB  - It is suggested that microRNAs play important roles in the development of various
      cancers. Here, we showed that miR-137 is downregulated in glioblastoma (GBM) cell
      lines and that low levels of miR-137 are associated with a poor prognostic
      phenotype of GBM patients. Ectopic expression of miR-137 significantly inhibited
      GBM cell proliferation and angiogenesis. In addition, ectopic expression of miR
      137 inhibited tumor growth and angiogenesis in a SCID mouse xenograft model. EZH2
      was identified as a direct target of miR-137 by using luciferase reporter and
      Western blot assays, and EZH2 overexpression can rescue the inhibitory effect of
      miR-137 on cell proliferation and angiogenesis. Furthermore, tumor samples from
      GBM patients showed an inverse relationship between miR-137 and EZH2 levels. Our
      results suggest that miR-137 may serve as a biomarker in GBM, and the modulation
      of its activity may represent a novel therapeutic strategy for the treatment of
      GBM patients.

PMID- 25939440
TI  - Calcification in high grade gliomas treated with bevacizumab.
AB  - Calcification is a rare phenomenon in high grade glioma (HGG). CT scans are
      sensitive to mineralization but used infrequently for tumor assessment in the MRI
      era. The presence of calcification can be overlooked on routine MRI.
      Calcification may reflect chronicity and natural changes in the tumor or its
      milieu over time and may be accelerated by certain treatments. Calcification may
      have clinical significance which could signal potential risk for stroke or
      hemorrhage related to particular therapies; or it may be a positive prognostic
      factor for treatment response. The true incidence and relevance of calcification
      in HGG and relation to therapy is unclear. During treatment of HGG patients with
      bevacizumab (BVZ) we observed significant tumor calcification on brain CT. We
      performed a retrospective review of HGG patients treated with BVZ to quantitate
      the incidence of calcification in this group compared to those treated with
      cytotoxic therapy alone. Sixty-two patients with progressive HGG were treated
      with BVZ and a cytotoxic agent. Among 19 patients treated for 6+ months, 12 had a
      CT scan performed. We observed an unexpected phenomenon of calcification in the
      CT scans of several patients. We were also able to comparatively quantitate the
      incidence of calcification in a control group of primary glioblastoma (GB)
      patients not exposed to BVZ therapy. The incidence of calcification in the
      general GB population is increased with longer survival. The phenomenon is
      increased with anti-angiogenic therapy for brain tumors. Calcification may have
      significance as a predictor for treatment response. 

PMID- 25939441
TI  - MRI findings and pathological features in early-stage glioblastoma.
AB  - Magnetic resonance imaging (MRI) is an important diagnostic tool for
      glioblastoma, with almost all cases showing characteristic imaging findings such
      as a heterogeneous-ring enhanced pattern associated with significant edema.
      However, MRI findings for early-stage glioblastoma are less clear. In this study,
      a retrospective review of MRI findings in five patients showed slight T2WI signal
      changes on initial scans that developed into typical imaging findings of a ring
      like or heterogeneously enhanced bulky tumor within 6 months. The diagnoses based
      on initial MRI were low grade glioma in three cases, venous thrombosis in one
      case, and uncertain in one case. Four cases were treated with gross total
      resection, while one case underwent biopsy. Immunohistochemical examinations
      showed that two cases were p53-positive, and that all cases were IDH1 R132H
      negative and had overexpression of EGFR. FISH analysis showed that all cases were
      1p19q LOH-negative. De novo glioblastoma was the final diagnosis in all cases.
      Our results show that initial MRI findings in early-stage glioblastoma of small
      ill-defined T2WI hyperintense lesions with poor contrast develop to bulky mass
      lesions with typical findings for glioblastoma in as short a period as 2.5
      months. The early MRI findings are difficult to distinguish from those for non
      neoplastic conditions, including ischemic, degenerative or demyelinating
      processes. Thus, there is a need for proactive diagnosis of glioblastoma using
      short-interval MRI scans over several weeks, other imaging modalities, and biopsy
      or resection, particularly given the extremely poor prognosis of this disease.

PMID- 25939442
TI  - Disclosing food allergy status in schools: health-related stigma among school
      children in Ontario.
AB  - In 2006, 3 years after the tragic death of 13-year-old Sabrina Shannon, the
      Province of Ontario (Canada) passed Sabrina's Law ushering in a new era of focus
      and concern for severe food allergic children at risk of anaphylaxis. Questions
      were raised at the time regarding the potential of doing more harm than good with
      the new legislation. This paper reports the experiences of health-related stigma
      among food allergic children at risk of anaphylaxis who were required to disclose
      their health status under this new legislation. In 2008, in-depth interviews were
      conducted with 20 children and youth and their parents in order to explore the
      experiences living with a severe food allergy. This particular study explores
      their experiences of felt and enacted stigma in the school setting as a result of
      the disclosure process. Interviews were tape recorded with permission and
      transcribed for subsequent thematic analysis using NVIVO, a qualitative analysis
      software package. Results indicate that participants were stigmatised as a result
      of protective school policies under the law, and that created tension between
      their physical safety and social well-being. Sabrina's Law also led to a cultural
      shift in awareness of food allergies that resulted in some participants
      normalising their health status, offering promising directions for the future.

PMID- 25939443
TI  - An Analysis of the Time Course of Lexical Processing During Reading.
AB  - Reingold, Reichle, Glaholt, and Sheridan (2012) reported a gaze-contingent eye
      movement experiment in which survival-curve analyses were used to examine the
      effects of word frequency, the availability of parafoveal preview, and initial
      fixation location on the time course of lexical processing. The key results of
      these analyses suggest that lexical processing begins very rapidly (after
      approximately 120 ms) and is supported by substantial parafoveal processing (more
      than 100 ms). Because it is not immediately obvious that these results are
      congruent with the theoretical assumption that words are processed and identified
      in a strictly serial manner, we attempted to simulate the experiment using the E
      Z Reader model of eye-movement control (Reichle, 2011). These simulations were
      largely consistent with the empirical results, suggesting that parafoveal
      processing does play an important functional role by allowing lexical processing
      to occur rapidly enough to mediate direct control over when the eyes move during
      reading. 

PMID- 25939444
TI  - Survival benefit with IMRT following narrow-margin hepatectomy in patients with
      hepatocellular carcinoma close to major vessels.
AB  - BACKGROUND & AIMS: To investigate the role of post-operative intensity-modulated
      radiotherapy (IMRT) in patients receiving narrow-margin hepatectomy for
      hepatocellular carcinoma (HCC) located close to the major vessels. METHODS: This
      exploratory study involved 181 HCC patients. Of them, 116 were treated with
      narrow-margin (<1.0 cm) hepatectomy. Thirty-three of the 116 underwent
      postoperative IMRT (Group A), while 83 did not receive radiotherapy (Group B).
      The remaining 65 patients underwent wide-margin (>=1.0 cm) hepatectomy (Group C).
      Prognosis and patterns of recurrence were assessed in the three groups. RESULTS:
      The 3-year overall survival (OS) and disease-free survival (DFS) rates were 89.1
      and 64.2% in Group A, 67.7 and 52.2% in Group B and 86.0 and 60.1% in Group C
      respectively. The OS and DFS of Group A and Group C patients surpassed those of
      Group B patients (Group A vs. B, P = 0.009 and P = 0.038; and Group C vs. B, P =
      0.002 and P = 0.010). Patients in Groups A and C experienced significantly fewer
      early recurrences than did patients in Group B (P = 0.002). Furthermore, patients
      in Groups A and C experienced substantially fewer intrahepatic marginal (P =
      0.048) and diffuse recurrences (P = 0.018) and extrahepatic metastases (P =
      0.038) than did patients in Group B. No patient developed radiation-induced liver
      disease. CONCLUSIONS: Post-operative IMRT following narrow-margin hepatectomy may
      be a favourable therapy for both its safety profile and clinical benefit in
      patients with HCC located close to the major vessels.

PMID- 25939445
TI  - Glanzmann's thrombasthenia: meeting the anticoagulation challenge.

PMID- 25939446
TI  - Coordination Site Disorder in Spinel-Type LiMnTiO4.
AB  - LiMnTiO4 was prepared through solid-state syntheses employing different heating
      and cooling regimes. Synchrotron X-ray and neutron powder diffraction data found
      quenched LiMnTiO4 to form as single phase disordered spinel (space group Fd3m),
      whereas slowly cooled LiMnTiO4 underwent partial phase transition from Fd3m to
      P4332. The phase behavior of quenched and slowly cooled LiMnTiO4 was confirmed
      through variable-temperature synchrotron X-ray and neutron powder diffraction
      measurements. The distribution of Li between tetrahedral and octahedral sites was
      determined from diffraction data. Analysis of the Mn/Ti distribution in addition
      required Mn and Ti K-edge X-ray absorption near-edge structure spectra. These
      revealed the presence of Mn(3+) in primarily octahedral and Ti(4+) in octahedral
      and tetrahedral environments, with very slight variations depending on the
      synthesis conditions. Magnetic measurements indicated the dominance of
      antiferromagnetic interactions in both the slowly cooled and quenched samples
      below 4.5 K. 

PMID- 25939447
TI  - Validation of the ASSIST for Detecting Unhealthy Alcohol Use and Alcohol Use
      Disorders in Urgent Care Patients.
AB  - BACKGROUND: Screening and brief intervention (SBI) is effective in reducing
      alcohol use, particularly among moderate risk patients. Results of SBI are
      inconsistent among patients with alcohol use disorders (AUDs). The Alcohol,
      Smoking, and Substance Involvement Screening Test (ASSIST) is used as a screening
      tool in many existing SBI programs. ASSIST validation studies have identified
      risk level cutoff scores using criteria for AUD and have not included a criterion
      measure for at-risk drinking (ARD), the group for whom SBI is most effective.
      This study examines the ability of the ASSIST to identify unhealthy alcohol use
      (ARD or AUD) and AUD in patients presenting to urgent care. METHODS: Data were
      obtained from interviews with 442 adult drinkers presenting to 1 of 3 urgent care
      clinics. Subjects completed the ASSIST, a 90-day timeline follow-back interview
      to detect ARD, and a modified Diagnostic Interview Schedule to identify AUD.
      Validity measures compared the specificity and sensitivity of cutoff scores for
      the ASSIST in detecting unhealthy alcohol use and AUDs. RESULTS: The optimal
      ASSIST score for detecting unhealthy alcohol use is 6+ for males (sensitivity and
      specificity 68 and 66%, respectively) and 5+ for females (62%/70%). Sensitivity,
      specificity, and receiver operating characteristic values were lower than those
      previously reported for the Alcohol Use Disorders Identification Test (AUDIT).
      For AUD, the optimal ASSIST cutoff scores are 10+ for males (63%/85%) and 9+ for
      females (63%/85%). While higher scores provided increased specificity, thereby
      reducing the percentage of false positives, sensitivity dropped sharply as scores
      increased. CONCLUSIONS: Optimal ASSIST cutoff scores for unhealthy alcohol use
      are lower than those commonly used in many SBI programs. Use of lower ASSIST
      cutoff scores may increase detection of unhealthy alcohol use and increase the
      numbers served by SBI programs.

PMID- 25939448
TI  - Psychometric evaluation of the German Version of the Supportive Care Needs Survey
      for Partners and Caregivers (SCNS-P&C-G) of cancer patients.
AB  - This study aimed for psychometric validation of the German version of the
      Supportive Care Needs Survey for Partners and Caregivers (SCNS-P&C-G). In- and
      outpatients with lung, urological and gastrointestinal cancer at Heidelberg
      University Hospital in Germany and in each case one relevant caregiver were asked
      to complete a set of questionnaires assessing their unmet needs together with
      distress, depression, anxiety and caregiver strain. In addition, medical data of
      the patients were collected. Fully completed questionnaires were received from
      188 pairs of patients and their caregivers. Using exploratory factor analysis,
      four domains of unmet needs were identified with an appropriate variance
      explanation (58.7%) and acceptable (>0.70) internal consistencies (alpha = 0.95
      to 0.76) for each domain. Convergent validity was found with respect to
      significant positive correlations (>0.40) of the SCNS-P&C-G domains with
      caregivers' anxiety, depression and strain. Although poorer health status of the
      patient indicated more unmet caregiver needs, this finding was not consistent for
      all need domains. Overall, associations were only moderate to weak pointing out
      the necessity of a separate screening for caregivers' needs. The findings of this
      study support that the SCNS-P&C-G is an appropriate research instrument to assess
      caregivers' needs on different domains throughout the disease trajectory. 

PMID- 25939449
TI  - Transition-metal-free, ambient-pressure carbonylative cross-coupling reactions of
      aryl halides with potassium aryltrifluoroborates.
AB  - We disclose an unprecedented transition-metal-free carbonylative cross coupling
      of aryl halides with potassium aryl trifluoroborates even at atmospheric pressure
      of carbon monoxide. This protocol is efficient, operationally simple, and shows
      wide scope with regard to both aryl halides and potassium aryl trifluoroborates
      containing a series of active functional groups. 

PMID- 25939450
TI  - Guanidinylations of albumin decreased binding capacity of hydrophobic
      metabolites.
AB  - AIM: As post-translational modifications of proteins may have an impact on the
      pathogenesis of diseases such as atherosclerosis, diabetes mellitus and chronic
      kidney disease (CKD), post-translational modifications are currently gaining
      increasing interest. In this study, a comprehensive method for analysis of these
      post-translational modifications is established for the clinical diagnostic
      routine. METHODS: Here, we analysed albumin - the most abundant plasma protein in
      human - isolated from patients with CKD and healthy controls by chromatographic
      steps and identified by MALDI mass spectrometry. Post-translational modifications
      of albumin were identified after digestion by analysing mass signal shifts of
      albumin peptides using pertinent mass databases. RESULTS: Albumin isolated from
      plasma of patients with CKD but not from healthy control subjects was
      specifically post-translationally modified by guanidinylation of lysines at
      positions 249, 468, 548, 565 and 588. After identification of guanidinylations as
      post-translational modifications of albumin isolated from patients with CKD,
      these modifications were quantified by mass spectrometry demonstrating a
      significant increase in the corresponding mass signal intensities in patients
      with CKD compared to healthy controls. The relative amount of guanidinylation of
      lysine at position 468 in patients with CKD was determined as 63 +/- 32% (N = 3).
      Subsequently, we characterized the pathophysiological impact of the post
      translational guanidinylation on the binding capacity of albumin for
      representative hydrophobic metabolic waste products. In vitro guanidinylation of
      albumin from healthy control subjects caused a decreased binding capacity of
      albumin in a time-dependent manner. Binding of indoxyl sulphate (protein-bound
      fraction) decreased from 82 +/- 1% of not post-translationally modified albumin
      to 56 +/- 1% after in vitro guanidinylation (P < 0.01), whereas the binding of
      tryptophan decreased from 20 to 4%. These results are in accordance with the
      binding of indoxyl sulphate to albumin from healthy control subjects and patients
      with CKD (88 +/- 3 vs. 74 +/- 10, P < 0.01). Thus, in vitro post-translational
      guanidinylation of albumin had a direct effect on the binding capacity of
      hydrophobic metabolites such as indoxyl sulphate and tryptophan. CONCLUSION: We
      used a mass spectrometry-based method for the characterization of post
      translational modification and demonstrated the pathophysiological impact of a
      representative post-translational modification of plasma albumin. The data
      described in this study may help to elucidate the pathophysiological role of
      protein modifications.

PMID- 25939451
TI  - Undescended testis: Level of knowledge among potential referring health-care
      providers.
AB  - AIM: Studies report that most boys with undescended testis(UDT) are referred and
      operated beyond the recommended age of 1 year, possibly due to lack of awareness
      of treatment guidelines. We investigate the level of knowledge of UDT among
      potential referring health-care providers. METHOD: We devised a survey on the
      clinical features and appropriate management of UDT. Using convenience sampling,
      we approached health-care professionals with regular contact with paediatric
      patients and final year medical students. Respondents were allowed to remain
      anonymous. They were categorised according to specialty and level of
      experience/training. RESULTS: Of 1179 approached, 203 responded. Thirty-six (24%)
      of 149 qualified doctors had never seen a case of UDT. Median score was 6 (range
      1-9). There was no significant difference in scores when comparing specialty.
      Mean scores decreased significantly in trend according to level of experience.
      When questioned regarding timings of referral and orchidopexy, 24% of qualified
      doctors would not refer until 9 months of age, and 66% thought orchidopexy should
      be done after 1 year old. Half would stop examining for UDT after 2 years old.
      CONCLUSIONS: Inexperience with UDT and outdated knowledge may contribute to
      delays in referral for UDT. Many would stop examining for UDT at 2 years old,
      placing undue reliance on accurate physical examination in early childhood and
      indicating lack of awareness of the ascending testis. Community health
      initiatives must emphasise recent changes in guidelines for management of UDT.

PMID- 25939453
TI  - The Assessment of African Swine Fever Virus Risk to Belgium Early 2014, using the
      Quick and Semiquantitative Pandora Screening Protocol.
AB  - A risk assessment was organized during the early EU ASF outbreaks of early 2014
      (February-April) and performed in cooperation with 15 Belgian and European
      experts on ASFV and its epidemiology in pigs/wild boar. African swine fever (ASF)
      is considered as one of the most dangerous infectious pig diseases, causing many
      outbreaks. Since the end of 2013 - early 2014, several outbreaks within the
      European Union (Lithuania, Poland, Estonia and Latvia) were reported to OIE,
      which prompted several risk assessments by (inter)national bodies and scientists.
      In this study, the open source, semiquantitative Pandora risk assessment tool was
      used for a quick overall screening of the risk posed by ASF to Belgium early
      2014. A set of integrated risk scores was calculated within the Pandora
      framework. Experts scored the questions and uncertainty levels in the Pandora
      modules individually, after which the calculations were performed and averaged
      scores were used within pre-defined risk scales to define and visualize the ASF
      risk to Belgium. Emergence risk was considered low (Pandora score 0.29), while
      disease consequences were deemed high (0.93); the resulting multiplicative
      overall risk of ASFV for Belgium was low (0.27). The Belgian experts tended to
      give lower risk scores than the European experts, especially for entry risk and
      trade/public opinion consequences. These risk scores are further interpreted with
      a due consideration of the qualitative data in the expert remarks and of other
      ASF risk assessments. The results are similar to more extensive and elaborate
      risk assessment models/procedures which may require more time and resources. The
      Pandora tool allows sequential updates to monitor (rates of) increasing risk and
      provides information for risk managers to organize targeted control.

PMID- 25939454
TI  - Asthma control in children is associated with nasal symptoms, obesity, and health
      insurance: a nationwide survey.
AB  - BACKGROUND: This study aimed to estimate the prevalence of asthma control and
      determinants of poor control in the Portuguese pediatric population (<18 years);
      secondarily, we described asthma-related healthcare services and medication use.
      METHODS: Data of 98 children with current asthma, from the second phase of a
      nationwide population-based telephone survey (INAsma study), were analyzed.
      Asthma control definition was based on GINA criteria, grouping partially
      controlled and uncontrolled asthma as 'not-controlled asthma' (NCA). We used
      multivariate logistic regression to study factors associated with NCA and with
      unscheduled medical visits for asthma. RESULTS: About half of the children had
      NCA (49%, 95% CI 39-59%). In the multivariate model, risk factors for NCA were as
      follows: substantial nasal symptoms (a OR 6.80), overweight/obesity (a OR 3.44),
      and not having health insurance (a OR 3.78). All the children with NCA had nasal
      symptoms, and the lack of asthma control was also associated with the increasing
      number of nasal symptoms (p < 0.001). In the previous year, 90% (95% CI 84-96%)
      of children with current asthma had healthcare visits and 67% (95% CI 58-77%)
      used medication for asthma. The risk of unscheduled medical visits was higher in
      children with nasal symptoms (a OR 3.63) and in those without health insurance (a
      OR 2.79), and lower in adolescents (a OR 0.19). CONCLUSIONS: Half of the children
      with asthma were poorly controlled. Nasal symptoms and obesity are important
      determinants of asthma control. Children without health insurance are at greater
      risk of poor asthma outcomes; this association is reported for the first time in
      a European country.

PMID- 25939452
TI  - Adenosine A(2A) receptors are necessary and sufficient to trigger memory
      impairment in adult mice.
AB  - BACKGROUND AND PURPOSE: Caffeine (a non-selective adenosine receptor antagonist)
      prevents memory deficits in aging and Alzheimer's disease, an effect mimicked by
      adenosine A2 A receptor, but not A1 receptor, antagonists. Hence, we investigated
      the effects of adenosine receptor agonists and antagonists on memory performance
      and scopolamine-induced memory impairment in mice. EXPERIMENTAL APPROACH: We
      determined whether A2 A receptors are necessary for the emergence of memory
      impairments induced by scopolamine and whether A2 A receptor activation triggers
      memory deficits in naive mice, using three tests to assess short-term memory,
      namely the object recognition task, inhibitory avoidance and modified Y-maze. KEY
      RESULTS: Scopolamine (1.0 mg.kg(-1) , i.p.) impaired short-term memory
      performance in all three tests and this scopolamine-induced amnesia was prevented
      by the A2 A receptor antagonist (SCH 58261, 0.1-1.0 mg.kg(-1) , i.p.) and by the
      A1 receptor antagonist (DPCPX, 0.2-5.0 mg.kg(-1) , i.p.), except in the modified
      Y-maze where only SCH58261 was effective. Both antagonists were devoid of effects
      on memory or locomotion in naive rats. Notably, the activation of A2 A receptors
      with CGS 21680 (0.1-0.5 mg.kg(-1) , i.p.) before the training session was
      sufficient to trigger memory impairment in the three tests in naive mice, and
      this effect was prevented by SCH 58261 (1.0 mg.kg(-1) , i.p.). Furthermore,
      i.c.v. administration of CGS 21680 (50 nmol) also impaired recognition memory in
      the object recognition task. CONCLUSIONS AND IMPLICATIONS: These results show
      that A2 A receptors are necessary and sufficient to trigger memory impairment and
      further suggest that A1 receptors might also be selectively engaged to control
      the cholinergic-driven memory impairment.

PMID- 25939455
TI  - Could a trace mineral deficiency be associated with congenital chondrodystrophy
      of unknown origin (CCUO) in beef cattle in Australia?
AB  - Congenital chondrodystrophy of unknown origin (CCUO) has been reported in beef
      cattle worldwide. A trace mineral deficiency in pregnant dams has been suggested
      as causing the deformities seen in CCUO calves. An extended outbreak of CCUO in
      Australia between 2002 and 2009 provided an opportunity to examine the pattern of
      trace mineral status in gestating cows and the effect of parenteral trace mineral
      supplementation on a herd at risk of CCUO calves. A property with a strong
      history of CCUO was identified from a previous case-control study. A randomly
      selected sample of multiparous (8 to 10 years old) Angus and Angus cross cows (n
      = 20) was assigned to control (no injection) or supplement group given three
      injections at the recommended dose rate of chelated mineral supplement (Mn, Zn,
      Cu and Se) at 6-week intervals in mid- to late gestation. Liver biopsies were
      performed to measure liver Mn, Zn, Cu and Fe at each injection time and 1 month
      post-calving. Pasture samples were also collected for analysis. Supplemented cows
      had higher liver Cu levels compared to control cows (p < 0.001), but there was no
      difference between supplement and control cows for liver Zn, Fe or Mn. Liver Cu
      (p < 0.001), Fe (p < 0.001) and Zn (p < 0.001) fell during gestation and liver Mn
      increased after calving (p < 0.001). Three cows from the control group and two
      from the supplement group had liver zinc levels below the normal values at the
      end of the trial. Two cows from the control group and one from the treatment
      group gave birth to cows with signs of CCUO including superior brachygnathia. All
      cows except one from the control group had rough dry coats with excessive dander.
      The role of trace mineral status in the birth of CCUO calves, especially the role
      of zinc deficiency, requires further investigation.

PMID- 25939456
TI  - Multitasking: Effects of processing multiple auditory feature patterns.
AB  - ERPs and behavioral responses were measured to assess how task-irrelevant sounds
      interact with task processing demands and affect the ability to monitor and track
      multiple sound events. Participants listened to four-tone sequential frequency
      patterns, and responded to frequency pattern deviants (reversals of the pattern).
      Irrelevant tone feature patterns (duration and intensity) and respective pattern
      deviants were presented together with frequency patterns and frequency pattern
      deviants in separate conditions. Responses to task-relevant and task-irrelevant
      feature pattern deviants were used to test processing demands for irrelevant
      sound input. Behavioral performance was significantly better when there were no
      distracting feature patterns. Errors primarily occurred in response to the to-be
      ignored feature pattern deviants. Task-irrelevant elicitation of ERP components
      was consistent with the error analysis, indicating a level of processing for the
      irrelevant features. Task-relevant elicitation of ERP components was consistent
      with behavioral performance, demonstrating a "cost" of performance when there
      were two feature patterns presented simultaneously. These results provide
      evidence that the brain tracked the irrelevant duration and intensity feature
      patterns, affecting behavioral performance. Overall, our results demonstrate that
      irrelevant informational streams are processed at a cost, which may be considered
      a type of multitasking that is an ongoing, automatic processing of task
      irrelevant sensory events. 

PMID- 25939457
TI  - Poor correlation between bioelectrical impedance analysis and post illness weight
      gain in gastroenteritis.

PMID- 25939458
TI  - Alteration of cartilage surface collagen fibers differs locally after
      immobilization of knee joints in rats.
AB  - The purpose of this study was to examine the ultrastructural changes of surface
      cartilage collagen fibers, which differ by region and the length of the
      experimental period in an immobilization model of rat. Male Wistar rats were
      randomly divided into histological or macroscopic and ultrastructural assessment
      groups. The left knees of all the animals were surgically immobilized by external
      fixation for 1, 2, 4, 8 or 16 weeks (n = 5/time point). Sagittal histological
      sections of the medial mid-condylar region of the knee were obtained and assessed
      in four specific regions (contact and peripheral regions of the femur and tibia)
      and two zones (superficial and deep). To semi-quantify the staining intensity of
      the collagen fibers in the cartilage, picrosirius red staining was used. The
      cartilage surface changes of all the assessed regions were investigated by
      scanning electron microscopy (SEM). From histological and SEM observations, the
      fibrillation and irregular changes of the cartilage surface were more severe in
      the peripheral region than in the contact region. Interestingly, at 16 weeks post
      immobilization, we observed non-fibrous structures at both the contact and
      peripheral regions. The collagen fiber staining intensity decreased in the
      contact region compared with the peripheral region. In conclusion, the alteration
      of surface collagen fiber ultrastructure and collagen staining intensity differed
      by the specific cartilage regions after immobilization. These results demonstrate
      that the progressive degeneration of cartilage is region specific, and depends on
      the length of the immobilization period. 

PMID- 25939459
TI  - Phylogeny, Diversity, Distribution, and Host Specificity of Haemoproteus spp.
      (Apicomplexa: Haemosporida: Haemoproteidae) of Palaearctic Tortoises.
AB  - A complex wide-range study on the haemoproteid parasites of chelonians was
      carried out for the first time. Altogether, 811 samples from four tortoise
      species from an extensive area between western Morocco and eastern Afghanistan
      and between Romania and southern Syria were studied by a combination of
      microscopic and molecular-genetic methods. Altogether 160 Haemoproteus-positive
      samples were gathered in the area between central Anatolia and eastern
      Afghanistan. According to variability in the cytochrome b gene, two monophyletic
      evolutionary lineages were distinguished; by means of microscopic analysis it was
      revealed that they corresponded to two previously described species-Haemoproteus
      anatolicum and Haemoproteus caucasica. Their distribution areas overlap only in a
      narrow strip along the Zagros Mts. range in Iran. This fact suggests the
      involvement of two different vector species with separated distribution.
      Nevertheless, no vectors were confirmed. According to phylogenetic analyses, H.
      caucasica represented a sister group to H. anatolicum, and both of them were most
      closely related to H. pacayae and H. peltocephali, described from South American
      river turtles. Four unique haplotypes were revealed in the population of H.
      caucasica, compared with seven haplotypes in H. anatolicum. Furthermore, H.
      caucasica was detected in two tortoise species, Testudo graeca and Testudo
      horsfieldii, providing evidence that Haemoproteus is not strictly host-specific
      to the tortoise host species. 

PMID- 25939460
TI  - Markov model for characterizing neuropsychologic impairment and Monte Carlo
      simulation for optimizing efavirenz therapy.
AB  - The study was undertaken to develop a pharmacokinetic-pharmacodynamic model to
      characterize efavirenz-induced neuropsychologic impairment, given preexistent
      impairment, which can be used for the optimization of efavirenz therapy via Monte
      Carlo simulations. The modeling was performed with NONMEM 7.2. A 1-compartment
      pharmacokinetic model was fitted to efavirenz concentration data from 196 Ugandan
      patients treated with a 600-mg daily efavirenz dose. Pharmacokinetic parameters
      and area under the curve (AUC) were derived. Neuropsychologic evaluation of the
      patients was done at baseline and in week 2 of antiretroviral therapy. A discrete
      time 2-state first-order Markov model was developed to describe neuropsychologic
      impairment. Efavirenz AUC, day 3 efavirenz trough concentration, and female sex
      increased the probability (P01) of neuropsychologic impairment. Efavirenz oral
      clearance (CL/F) increased the probability (P10) of resolution of preexistent
      neuropsychologic impairment. The predictive performance of the reduced (final)
      model, given the data, incorporating AUC on P01and CL /F on P10, showed that the
      model adequately characterized the neuropsychologic impairment observed with
      efavirenz therapy. Simulations with the developed model predicted a 7% overall
      reduction in neuropsychologic impairment probability at 450 mg of efavirenz. We
      recommend a reduction in efavirenz dose from 600 to 450 mg, because the 450-mg
      dose has been shown to produce sustained antiretroviral efficacy. 

PMID- 25939461
TI  - Editorial: post hoc analysis of SONIC trial.

PMID- 25939462
TI  - Editorial: post hoc analysis of SONIC trial--authors' reply.

PMID- 25939463
TI  - Editorial: functional gastrointestinal disorders and body mass index.

PMID- 25939464
TI  - Editorial: hepatocellular carcinoma--a rare complication of hepatic venous
      outflow tract obstruction.

PMID- 25939465
TI  - Editorial: hepatocellular carcinoma--a rare complication of hepatic venous
      outflow tract obstruction---authors' reply.

PMID- 25939466
TI  - Editorial: environmental risk factors for PSC with and without IBD--the story
      unfolds.

PMID- 25939467
TI  - Editorial: dynamic changes of the inflammation-based index predict mortality
      following chemoembolisation for hepatocellular carcinoma.

PMID- 25939468
TI  - Editorial: dynamic changes of the inflammation-based index predict mortality
      following chemoembolisation for hepatocellular carcinoma--authors' reply.

PMID- 25939469
TI  - Letter: bismuth, levofloxacin, amoxicillin, PPI quadruple therapy is not an
      effective first or second line regimen in the presence of levofloxacin
      resistance.

PMID- 25939470
TI  - Letter: bismuth, levofloxacin, amoxicillin, PPI quadruple therapy is not an
      effective first or second-line regimen in the presence of levofloxacin resistance
      -authors' reply.

PMID- 25939471
TI  - Efficacy of hypnotherapy in one thousand patients with irritable bowel syndrome.

PMID- 25939472
TI  - Letter: efficacy of hypnotherapy in one thousand patients with irritable bowel
      syndrome--authors' reply.

PMID- 25939473
TI  - Letter: proton pump inhibitor treatment and increased mortality in cirrhotic
      patients.

PMID- 25939474
TI  - Letter: proton pump inhibitor treatment and increased mortality in cirrhotic
      patients--authors' reply.

PMID- 25939475
TI  - Tissue concentrations as the dose metric to assess potential toxic effects of
      metals in field-collected fish: Copper and cadmium.
AB  - The present study examined the available literature linking whole-body tissue
      concentrations with toxic effects in fish species for copper and cadmium. The
      variability in effect concentration for both copper and cadmium among species
      occurred within an order of magnitude for all responses, whereas the range for
      lethal toxicity based on water exposure spanned approximately 4 to 5 orders of
      magnitude. Fish tissue concentrations causing adverse effects were just above
      background concentrations, occurring between 1 MUg/g and 10 MUg/g for copper and
      0.1 MUg/g to 4 MUg/g for cadmium. The results also show that salmonids are
      especially sensitive to cadmium, which appears to be a function of chemical
      potency. No studies were found that indicated adverse effects without increases
      in whole-body concentration of these metals. This narrow range for dose-response
      implies that a toxicological spillover point occurs when the detoxification
      capacity of various tissues within the animal are exceeded, and this likely
      occurs at a similar whole-body concentration for all naively exposed fish
      species. Elevated whole-body concentrations in fish from the field may be
      indicative of possible acclimation to metals that may or may not result in
      effects for target species. Acclimation concentrations may be useful in that they
      signal excessive metal concentrations in water, sediment, or prey species for a
      given site and indicate likely toxic effects for species unable to acclimate to
      excess metal exposure. Using tissue residues as the dose metric for these metals
      provides another line of evidence for assessing impaired ecosystems and greater
      confidence that hazard concentrations are protective for all fish species.

PMID- 25939476
TI  - Writing nanopatterns with electrochemical oxidation on redox responsive
      organometallic multilayers by AFM.
AB  - Nanoelectrochemical patterning of redox responsive organometallic
      poly(ferrocenylsilane) (PFS) multilayers is demonstrated by electrochemical dip
      pen lithography (EDPN). Local electrochemical oxidation and Joule heating of PFS
      multilayers from the tip are considered as relevant mechanisms related to
      structure generation. The influence of applied bias potential, tip velocity, and
      multilayer thickness on the pattern height and width were investigated. 

PMID- 25939477
TI  - Cleavage of hydrogen by activation at a single non-metal centre - towards new
      hydrogen storage materials.
AB  - Molecular surfaces of non-metal species are often characterized by both positive
      and negative regions of electrostatic potential (EP) at a non-metal centre. This
      centre may activate molecular hydrogen which further leads to the addition
      reaction. The positive EP regions at the non-metal centres correspond to sigma
      holes; the latter sites are enhanced by electronegative substituents. This is why
      the following simple moieties; PFH2, SFH, AsFH2, SeFH, BrF3, PF(CH3)2 and
      AsF(CH3)2, were chosen here to analyze the H2 activation and its subsequent
      splitting at the P, As, S, Se and Br centres. Also the reverse H-H bond reforming
      process is analyzed. MP2/aug-cc-pVTZ calculations were performed for systems
      corresponding to different stages of these processes. The sulphur centre in the
      SFH moiety is analyzed in detail since the potential barrier height for the
      addition reaction for this species is the lowest of the moieties analyzed here.
      The results of calculations show that the SFH + H2 -> SFH3 reaction in the gas
      phase is endothermic but it is exothermic in polar solvents. 

PMID- 25939478
TI  - Synthesis, characterization, photophysics and electrochemical study of
      luminescent iridium(III) complexes with isocyanoborate ligands.
AB  - A new series of cyclometalated iridium(III) complexes with isocyanoborate ligands
      [Ir(R2ppy)2(L)(CNBR'3)] (R = H or F; L = CNC6H4Cl-4 or PPh3; R' = Ph, C6F5 or
      C6H4Cl-4), [Ir(biqb)(ppy)(CNBR''3)] (R'' = C6F5 or C6H4Cl-4) and
      {Ir(ppy)2(CN)n[CNB(C6F5)3]2-n}(-) (n = 0 or 1) have been synthesized and
      characterized. Three of these complexes have also been structurally characterized
      by X-ray crystallography. The photophysical and electrochemical properties of
      these complexes have been investigated. The effects of isocyanoborate ligands on
      the luminescence properties of these iridium(III) complexes are also described.

PMID- 25939479
TI  - Collagen Fibrils and Proteoglycans of Macular Dystrophy Cornea: Ultrastructure
      and 3D Transmission Electron Tomography.
AB  - We report the ultrastructure and 3D transmission electron tomography of collagen
      fibrils (CFs), proteoglycans (PGs), and microfibrils within the CF of corneas of
      patients with macular corneal dystrophy (MCD). Three normal corneas and three MCD
      corneas from three Saudi patients (aged 25, 31, and 49 years, respectively) were
      used for this study. The corneas were processed for light and electron microscopy
      studies. 3D images were composed from a set of 120 ultrastructural images using
      the program "Composer" and visualized using the program "Visuliser Kai". 3D image
      analysis of MCD cornea showed a clear organization of PGs around the CF at very
      high magnification and degeneration of the microfibrils within the CF. Within the
      MCD cornea, the PG area in the anterior stroma was significantly larger than in
      the middle and posterior stroma. The PG area in the MCD cornea was significantly
      larger compared with the PG area in the normal cornea. The CF diameter and inter
      fibrillar spacing of the MCD cornea were significantly smaller compared with
      those of the normal cornea. Ultrastructural 3D imaging showed that the production
      of unsulfated keratin sulfate (KS) may lead to the degeneration of micro-CFs
      within the CFs. The effect of the unsulfated KS was higher in the anterior stroma
      compared with the posterior stroma. 

PMID- 25939480
TI  - Association of ERG and TMPRSS2-ERG with grade, stage, and prognosis of prostate
      cancer is dependent on their expression levels.
AB  - BACKGROUND: There is controversy in the literature on the role of the fusion
      TMPRSS2-ERG in the pathogenesis and progression of prostate cancer. The
      quantitative differences in TMPRSS2-ERG fusion expression have received very
      limited attention in the literature. METHODS: We have quantitatively analyzed the
      mRNA levels of TMPRSS2-ERG, ERG, PTEN, and AR (n = 83), as well as ERG
      immunostaining (n = 78) in a series of prostate tumors. RESULTS: Among the
      TMPRSS2-ERG cases (n = 57), high fusion levels were associated with GS >=8 (P =
      0.025). ERG mRNA overexpression was associated with GS >=8 (P = 0.047), and with
      stage T3-T4 tumors (P = 0.032). Among the ERG overexpressing cases (n = 54),
      higher expression levels were found in 92.3% of GS >=8 tumors (P = 0.02). ERG
      immunostaining, regardless of staining intensity, was also associated with high
      stage (P = 0.05). There was a statistical association between ERG immunostaining
      and PSA progression-free survival (Log Rank test, P = 0.048). Decreased PTEN
      expression was associated with TMPRSS2-ERG (P = 0.01), ERG mRNA overexpression (P
      = 0.003) and ERG immunostaining (P = 0.007). Furthermore, decreased PTEN
      expression, alone (P = 0.041) and also combined with TMPRSS2-ERG (P = 0.04) or
      with ERG overexpression (P = 0.04) was associated with GS >=7 tumors.
      CONCLUSIONS: Although more studies are needed to further clarify their role, our
      findings emphasize that the expression levels of the TMPRSS2-ERG fusion and ERG
      mRNA, rather than their mere presence, are related to a more aggressive
      phenotype, have an effect on prognosis and could be molecular markers of
      progression for prostate cancer. Furthermore, ERG immunohistochemistry could be
      also a potentially useful prognostic factor.

PMID- 25939481
TI  - Dietary restriction decreases coenzyme Q and ubiquinol potentially via changes in
      gene expression in the model organism C. elegans.
AB  - Dietary restriction (DR) is a robust intervention that extends both health span
      and life span in many organisms. Ubiquinol and ubiquinone represent the reduced
      and oxidized forms of coenzyme Q (CoQ). CoQ plays a central role in energy
      metabolism and functions in several cellular processes including gene expression.
      Here we used the model organism Caenorhabditis elegans to determine level and
      redox state of CoQ and expression of genes in response to DR. We found that DR
      down-regulates the steady-state expression levels of several evolutionary
      conserved genes (i.e. coq-1) that encode key enzymes of the mevalonate and CoQ
      synthesizing pathways. In line with this, DR decreases the levels of total CoQ
      and ubiquinol. This CoQ-reducing effect of DR is obvious in adult worms but not
      in L4 larvae and is also evident in the eat-2 mutant, a genetic model of DR. In
      conclusion, we propose that DR reduces the level of CoQ and ubiquinol via gene
      expression in the model organism C. elegans.

PMID- 25939483
TI  - A coach's political use of video-based feedback: a case study in elite-level
      academy soccer.
AB  - This paper examines the video-based pedagogical practices of Terry (pseudonym), a
      head coach of a professional junior academy squad. Data were collected through 6
      in-depth, semi-structured interviews and 10 field observations of Terry's video
      based coaching in situ. Three embracing categories were generated from the data.
      These demonstrated that Terry's video-based coaching was far from apolitical.
      Rather, Terry strategically used performance analysis technologies to help fulfil
      various objectives and outcomes that he understood to be expected of him within
      the club environment. Kelchtermans' micropolitical perspective, Callero's work
      addressing role and Groom et al.'s grounded theory were primarily utilised to
      make sense of Terry's perceptions and actions. The findings point to the value of
      developing contextually grounded understandings of coaches' uses of video-based
      performance analysis technology. Doing so could better prepare coaches for this
      aspect of their coaching practice. 

PMID- 25939482
TI  - Cognitive screening among acute respiratory failure survivors: a cross-sectional
      evaluation of the Mini-Mental State Examination.
AB  - INTRODUCTION: The Mini-Mental State Examination (MMSE) is a common cognitive
      screening test, but its utility in identifying impairments in survivors of acute
      respiratory failure is unclear. The purpose of this study was to evaluate MMSE
      performance versus a concurrently administered detailed neuropsychological test
      battery in survivors of acute respiratory failure. METHODS: This cross-sectional
      analysis used data from the ARDSNet Long Term Outcomes Study (ALTOS) and
      Awakening and Breathing Controlled Trial (ABC). Participants were 242 survivors
      of acute respiratory failure. The MMSE and detailed neuropsychological tests were
      administered at 6 and 12 months post-hospital discharge for the ALTOS study, and
      at hospital discharge, 3 and 12 months for the ABC study. Overall cognitive
      impairment identified by the MMSE (score <24) was compared to impairments
      identified by the neuropsychological tests. We also matched orientation,
      registration, attention, memory and language domains on the MMSE to the
      corresponding neuropsychological test. Pairwise correlations, sensitivity,
      specificity, positive and negative predictive values, and agreement were
      assessed. RESULTS: Agreement between MMSE and neuropsychological tests for
      overall cognitive impairment was fair (42 to 80%). Specificity was excellent
      (>=93%), but sensitivity was poor (19 to 37%). Correlations between MMSE domains
      and corresponding neuropsychological tests were weak to moderate (6 months: r =
      0.11 to 0.28; 12 months: r = 0.09 to 0.34). The highest correlation between the
      MMSE and neuropsychological domains was for attention at 6 months (r = 0.28) and
      language at 12 months (r = 0.34). CONCLUSIONS: In acute respiratory failure
      survivors, the MMSE has poor sensitivity in detecting cognitive impairment
      compared with concurrently administered detailed neuropsychological tests. MMSE
      results in this population should be interpreted with caution.

PMID- 25939485
TI  - PGMD: a comprehensive manually curated pharmacogenomic database.
AB  - The PharmacoGenomic Mutation Database (PGMD) is a comprehensive manually curated
      pharmacogenomics database. Two major sources of PGMD data are peer-reviewed
      literature and Food and Drug Administration (FDA) and European Medicines Agency
      (EMA) drug labels. PGMD curators capture information on exact genomic location
      and sequence changes, on resulting phenotype, drugs administered, patient
      population, study design, disease context, statistical significance and other
      properties of reported pharmacogenomic variants. Variants are annotated into
      functional categories on the basis of their influence on pharmacokinetics,
      pharmacodynamics, efficacy or clinical outcome. The current release of PGMD
      includes over 117 000 unique pharmacogenomic observations, covering all 24
      disease superclasses and nearly 1400 drugs. Over 2800 genes have associated
      pharmacogenomic variants, including genes in proximity to intergenic variants.
      PGMD is optimized for use in annotating next-generation sequencing data by
      providing genomic coordinates for all covered variants, including Single
      Nucleotide Polymorphisms (SNPs), insertions, deletions, haplotypes, diplotypes,
      Variable Number Tandem Repeats (VNTR), copy number variations and structural
      variations. 

PMID- 25939484
TI  - Prediction of treatment response to adalimumab: a double-blind placebo-controlled
      study of circulating microRNA in patients with early rheumatoid arthritis.
AB  - At least 30% of patients with rheumatoid arthritis (RA) do not respond to
      biologic agents, which emphasizes the need of predictive biomarkers. We aimed to
      identify microRNAs (miRNAs) predictive of response to adalimumab in 180 treatment
      naive RA patients enrolled in the OPtimized treatment algorithm for patients with
      early RA (OPERA) Study, an investigator-initiated, prospective, double-blind
      placebo-controlled study. Patients were randomized to adalimumab 40 mg (n=89) or
      placebo-adalimumab (n=91) subcutaneously in combination with methotrexate.
      Expressions of 377 miRNAs were determined using TaqMan Human MicroRNA LDA, A Card
      v2.0 (Applied Biosystems). Associations between miRNAs and treatment response
      were tested using interaction analyses. MiRNAs with a P-value <0.05 using three
      different normalizations were included in a multivariate model. After backwards
      elimination, the combination of low expression of miR-22 and high expression of
      miR-886.3p was associated with EULAR good response. Future studies to assess the
      utility of these miRNAs as predictive biomarkers are needed. 

PMID- 25939486
TI  - Au@pNIPAM SERRS Tags for Multiplex Immunophenotyping Cellular Receptors and
      Imaging Tumor Cells.
AB  - Detection technologies employing optically encoded particles have gained much
      interest toward clinical diagnostics and drug discovery, but the portfolio of
      available systems is still limited. The fabrication and characterization of
      highly stable surface-enhanced resonance Raman scattering (SERRS)-encoded
      colloids for the identification and imaging of proteins expressed in cells are
      reported. These plasmonic nanostructures are made of gold octahedra coated with
      poly(N-isopropylacrylamide) microgels and can be readily encoded with Raman
      active dyes while retaining high colloidal stability in biofluids. A layer-by
      layer polyelectrolyte coating is used to seal the outer surface of the encoded
      particles and to provide a reactive surface for covalent conjugation with
      antibodies. The targeted multiplexing capabilities of the SERRS tags are
      demonstrated by the simultaneous detection and imaging of three tumor-associated
      surface biomarkers: epidermal growth factor receptor (EGFR), epithelial cell
      adhesion molecule (EpCAM), and homing cell adhesion molecule (CD44) by SERRS
      spectroscopy. The plasmonic microgels are able to discriminate tumor A431
      (EGFR+/EpCAM+/CD44+) and nontumor 3T3 2.2 (EGFR-/EpCAM-/CD44+) cells while
      cocultured in vitro. 

PMID- 25939488
TI  - An in vitro study on the biocompatibility of WE magnesium alloys.
AB  - Magnesium alloys are being actively studied for intravascular stent applications
      because of their good mechanical strength and biocompatibility. To rule out the
      high allergenicity of nickel and neurotoxicity of aluminum element, four kinds of
      WE magnesium alloys (where "W" represents the metallic element Y and "E"
      represents mixed rare earth (RE) elements; Y: 2.5, 5.0, 6.5, and 7.5 wt %; Nd:
      1.0, 2.6, 2.5, and 4.2 wt %; Zr: 0.8 wt %) were chosen for in vitro investigation
      of their biocompatibility using cell culture. The results showed that, with the
      increase of rare earth elements in WE magnesium alloys, fibrinogen adsorption
      decreased and coagulation function was improved. It was also found that WE
      magnesium alloys promoted the adhesion of endothelial cells. With the increase of
      adhesion time, adhered cell numbers increased gradually. With 25% extracts, all
      the WE alloys promoted cell migration, while 100% extracts were not conducive to
      cell migration. Based on the above results, WE magnesium alloys 5.0WE (5.0Y-2.6Nd
      0.8Zr) and 6.5WE (6.5Y-2.5Nd-0.8Zr) have better biocompatibility as compared with
      that with 2.5WE (2.5Y-1.0Nd-0.8Zr) and 7.5WE (7.5Y-4.2Nd-0.8Zr), and could be as
      the promising candidate materials for medical stent applications.

PMID- 25939489
TI  - Mechano-electrochemistry effects due to deformation of copper oxide films.
AB  - In an attempt to elucidate the relationship and underlying processes of metal
      oxidation under stress, we combined the electrochemical characterisation with
      Density-Functional-Theory (DFT) calculations to interrogate the (100) surface of
      copper. The oxidised (100) surface shows a missing-row reconstruction, which is
      believed to be driven by surface stress. Hence, additional mechanical stimuli
      might have a significant impact on the onset of Cu oxidation. We find that
      different surface sites respond differently to strain. Oads at the
      thermodynamically favoured high-coordination hollow site (O coordinated to four
      Cu) is stabilised by up to 130 meV by imposing 2% tensile strain onto the
      surface, while the low-coordination top site (O coordinated to one Cu) shows a
      markedly different sensitivity. By cramping into the hollow site, Oads induces
      compressive stress into the (100) surface, an effect that is largely absent for
      the adsorption at the top site. We also find that the thermodynamic advantage of
      reconstructive underpotential surface oxidation is diminished under tensile
      strain. Hence, imposing tensile stress counter-balances the oxygen induced
      surface stress, which might have an implication on the onset of bulk copper
      oxidation. Studying Cu(100) single crystal surfaces in perchloric acid using
      cyclic voltammetry, we were able to confirm sensitivity of the electrochemical
      response towards the elastic strain. 

PMID- 25939487
TI  - Declining liver graft quality threatens the future of liver transplantation in
      the United States.
AB  - National liver transplantation (LT) volume has declined since 2006, in part
      because of worsening donor organ quality. Trends that degrade organ quality are
      expected to continue over the next 2 decades. We used the United Network for
      Organ Sharing (UNOS) database to inform a 20-year discrete event simulation
      estimating LT volume from 2010 to 2030. Data to inform the model were obtained
      from deceased organ donors between 2000 and 2009. If donor liver utilization
      practices remain constant, utilization will fall from 78% to 44% by 2030,
      resulting in 2230 fewer LTs. If transplant centers increase their risk tolerance
      for marginal grafts, utilization would decrease to 48%. The institution of "opt
      out" organ donation policies to increase the donor pool would still result in
      1380 to 1866 fewer transplants. Ex vivo perfusion techniques that increase the
      use of marginal donor livers may stabilize LT volume. Otherwise, the number of
      LTs in the United States will decrease substantially over the next 15 years. In
      conclusion, the transplant community will need to accept inferior grafts and
      potentially worse posttransplant outcomes and/or develop new strategies for
      increasing organ donation and utilization in order to maintain the number of LTs
      at the current level.

PMID- 25939490
TI  - Posterior predictive checking of multiple imputation models.
AB  - Multiple imputation is gaining popularity as a strategy for handling missing
      data, but there is a scarcity of tools for checking imputation models, a critical
      step in model fitting. Posterior predictive checking (PPC) has been recommended
      as an imputation diagnostic. PPC involves simulating "replicated" data from the
      posterior predictive distribution of the model under scrutiny. Model fit is
      assessed by examining whether the analysis from the observed data appears typical
      of results obtained from the replicates produced by the model. A proposed
      diagnostic measure is the posterior predictive "p-value", an extreme value of
      which (i.e., a value close to 0 or 1) suggests a misfit between the model and the
      data. The aim of this study was to evaluate the performance of the posterior
      predictive p-value as an imputation diagnostic. Using simulation methods, we
      deliberately misspecified imputation models to determine whether posterior
      predictive p-values were effective in identifying these problems. When estimating
      the regression parameter of interest, we found that more extreme p-values were
      associated with poorer imputation model performance, although the results
      highlighted that traditional thresholds for classical p-values do not apply in
      this context. A shortcoming of the PPC method was its reduced ability to detect
      misspecified models with increasing amounts of missing data. Despite the
      limitations of posterior predictive p-values, they appear to have a valuable
      place in the imputer's toolkit. In addition to automated checking using p-values,
      we recommend imputers perform graphical checks and examine other summaries of the
      test quantity distribution. 

PMID- 25939492
TI  - A Crystalline Mesoporous Germanate with 48-Ring Channels for CO2 Separation.
AB  - One of the challenges in materials science has been to prepare crystalline
      inorganic compounds with mesopores. Although several design strategies have been
      developed to address the challenge, expansion of pore sizes in inorganic
      materials is more difficult compared to that for metal-organic frameworks.
      Herein, we designed a novel mesoporous germanate PKU-17 with 3D 48*16*16-ring
      channels by introducing two large building units (Ge10 and Ge7 clusters) into the
      same framework. The key for this design strategy is the selection of 2
      propanolamine (MIPA), which serves as the terminal species to promote the
      crystallization of Ge7 clusters. Moreover, it is responsible for the coexistence
      of Ge10 and Ge7 clusters. To our knowledge, the discovery of PKU-17 sets a new
      record in pore sizes among germanates. It is also the first germanate that
      exhibits a good selectivity toward CO2 over N2 and CH4 . 

PMID- 25939493
TI  - Polypeptide vesicles with densely packed multilayer membranes.
AB  - Multilamellar membranes are important building blocks for constructing self
      assembled structures with improved barrier properties, such as multilamellar
      lipid vesicles. Polymeric vesicles (polymersomes) have attracted growing
      interest, but multilamellar polymersomes are much less explored. Here, we report
      the formation of polypeptide vesicles with unprecedented densely packed
      multilayer membrane structures with poly(ethylene glycol)-block-poly(gamma-(4,5
      dimethoxy-2-nitrobenzyl)-l-glutamate) (PEG-b-PL), an amphiphilic diblock rod-coil
      copolymer containing a short PEG block and a short hydrophobic rod-like
      polypeptide segment. The polypeptide rods undergo smectic ordering with PEG
      buried between the hydrophobic polypeptide layers. The size of both blocks and
      the rigidity of the hydrophobic polypeptide block are critical in determining the
      membrane structures. Increase of the PEG length in PEG-b-PL results in the
      formation of bilayer sheets, while using random-coil polypeptide block leads to
      the formation of large compound micelles. UV treatment causes ester bond cleavage
      of the polypeptide side chain, which induces helix-to-coil transition, change of
      copolymer amphiphilicity, and eventual disassembly of vesicles. These polypeptide
      vesicles with unique membrane structures provide a new insight into self-assembly
      structure control by precisely tuning the composition and conformation of
      polymeric amphiphiles. 

PMID- 25939491
TI  - Clinical Scale Zinc Finger Nuclease-mediated Gene Editing of PD-1 in Tumor
      Infiltrating Lymphocytes for the Treatment of Metastatic Melanoma.
AB  - Programmed cell death-1 (PD-1) is expressed on activated T cells and represents
      an attractive target for gene-editing of tumor targeted T cells prior to adoptive
      cell transfer (ACT). We used zinc finger nucleases (ZFNs) directed against the
      gene encoding human PD-1 (PDCD-1) to gene-edit melanoma tumor infiltrating
      lymphocytes (TIL). We show that our clinical scale TIL production process yielded
      efficient modification of the PD-1 gene locus, with an average modification
      frequency of 74.8% (n = 3, range 69.9-84.1%) of the alleles in a bulk TIL
      population, which resulted in a 76% reduction in PD-1 surface-expression. Forty
      to 48% of PD-1 gene-edited cells had biallelic PD-1 modification. Importantly,
      the PD-1 gene-edited TIL product showed improved in vitro effector function and a
      significantly increased polyfunctional cytokine profile (TNFalpha, GM-CSF, and
      IFNgamma) compared to unmodified TIL in two of the three donors tested. In
      addition, all donor cells displayed an effector memory phenotype and expanded
      approximately 500-2,000-fold in vitro. Thus, further study to determine the
      efficiency and safety of adoptive cell transfer using PD-1 gene-edited TIL for
      the treatment of metastatic melanoma is warranted. 

PMID- 25939495
TI  - Transition of Care and Health-Related Outcomes in Pediatric-Onset Systemic Lupus
      Erythematosus.
AB  - OBJECTIVE: Transition from pediatric to adult care is a complex process and can
      negatively impact patients with chronic disease. We describe the transition
      experience of patients with pediatric-onset systemic lupus erythematosus (SLE)
      and its associated outcomes in adulthood. METHODS: A telephone survey of 41
      pediatric-onset SLE patients was conducted following their transition to adult
      care. Data on medical and social outcomes during and after the transition were
      collected. Health status was compared to retrospectively collected baseline data
      at pediatric discharge. RESULTS: The mean +/- SD followup interval was 5 +/- 3.7
      years; the mean +/- SD age at followup was 24 +/- 4.2 years. More than half of
      patients (22 of 41) experienced transition difficulties, primarily due to loss of
      insurance and emotional readjustment, which were associated with poor symptom
      control (P = 0.03) and multiple organ system involvement (P = 0.05) at followup.
      After the transition, most patients (35 of 41) were followed by an adult-care
      rheumatologist, and the majority (37 of 41) reported recent symptoms of active
      disease; 41% (13 of 29) had developed symptoms suggestive of new renal
      manifestations following transition. One-third (15 of 41) reported new or ongoing
      neuropsychiatric symptoms. Both renal and neuropsychiatric manifestations were
      associated with unemployment (P < 0.05). Direct referral by a pediatric
      rheumatologist was associated with fewer hospitalizations following transition (P
      = 0.04). CONCLUSION: The majority of patients transitioned successfully to adult
      rheumatologic care. Major challenges were loss of insurance and attachment to
      pediatric providers, highlighting the importance of a structured transition
      process that focuses on providing emotional and financial guidance. Disease
      activity in pediatric-onset SLE remains high throughout adulthood, with morbidity
      primarily related to renal and neuropsychiatric manifestations.

PMID- 25939494
TI  - Prevalence of oropharyngeal antibiotic-resistant flora among residents of aged
      care facilities: a pilot study.
AB  - Residents in 11 long-term care facilities, and presenting to a single tertiary
      hospital site, were sampled to estimate prevalence of oropharyngeal colonization
      with resistant Gram-negative bacteria. From 124 residents, only one isolate
      (0.8%; 95% confidence interval 0.0%, 4.4) was multi-resistant (an extended
      spectrum beta-lactamase producing Escherichia coli) indicating that different
      treatment recommendations for respiratory infections in this population may not
      be justified.

PMID- 25939496
TI  - Composite Sensor Particles for Tuned SERS Sensing: Microfluidic Synthesis,
      Properties and Applications.
AB  - Surface-enhanced Raman scattering (SERS) is a promising platform for particle
      based sensor signaling, and droplet-based microfluidic systems are particularly
      advantageous for control of the size and composition of micro- and nanoparticles.
      For controlled sensing application, a high homogeneity of the sensor particles is
      a key requirement, and the particles with functional properties demand for the
      preparation in a minimum number of synthesis steps. Frequently used coflow and
      flow focusing arrangements, however, produce the microparticles of only larger
      size. To address such concern for downscaling of particle size, which is crucial
      for strong sensing outcome, we have used a peculiar micro cross-flow arrangement
      here for generating the polymer microparticles of broad size range between 30 and
      600 MUm along with in situ embedded silver nanoparticles. Embedded silver acts as
      nuclei for additional silver enforcement via silver-catalyzed silver deposition
      in order to realize the composite microparticles for SERS sensing. The
      homogeneous size and spatial distribution of silver nanoparticles inside the
      matrix and enforcement over the surface together with controlled pore size
      provides a high and homogeneous loading of polymer composite sensor. Moreover,
      different parameters such as analytes concentration and particles size have been
      studied here for SERS sensing application of biochemical molecules (amino acids
      and vitamins). Overall, the platform for size-tuned droplets generation,
      synthesis of composite microparticles, mechanism for synchronized
      photopolymerization-photoreduction, tuned silver enforcement, and the impacts of
      different analytes on differently composed microparticles are systematically
      investigated in this paper. 

PMID- 25939497
TI  - Incidence of severe local anaesthetic toxicity and adoption of lipid rescue in
      Finnish anaesthesia departments in 2011-2013.
AB  - BACKGROUND: Although the incidence of severe local anaesthetic systemic toxicity
      (LAST) has been declining, the risk of LAST still remains. There are no national
      treatment guidelines for LAST in Finland. We performed a national survey of the
      occurrence of LAST and its treatment in 2011-2013. METHODS: A structured
      electronic questionnaire was sent to the anaesthesia department chiefs of all
      Finnish public hospitals (n = 45) in spring 2014. We collected information about
      the occurrence and outcome of LASTs and existence of treatment protocols.
      RESULTS: The questionnaire response rate was 100% covering approximately 95% of
      all regional anaesthesias managed by anaesthesiologists in Finnish hospitals. The
      total number of regional anaesthesias, excluding spinal anaesthesia, performed by
      anaesthesiologists was approximately 211,700 during the survey period. Fifteen
      cases of LAST were reported (0.7 : 10,000); all patients recovered without
      negative sequelae. Fourteen patients, in five of whom ultrasound guidance had
      been applied, developed central nervous system toxicity symptoms and only one
      cardiac symptoms. Lipid emulsion was given to this latter patient, and to four of
      the other 14. The relative risk (95% confidence intervals) for occurrence of LAST
      in non-academic hospital vs. university hospitals was 3.3 (1.0-10.3; P = 0.04).
      Treatment protocols for LAST included lipid emulsion in 47% of the departments.
      CONCLUSIONS: The incidence of LAST in Finland is very low. Several departments
      have adopted lipid emulsion treatment for LAST despite lack of national
      recommendations and knowledge of the possible mechanism of action.

PMID- 25939498
TI  - Clinical characterization of antiphospholipid syndrome by detection of IgG
      antibodies against beta2 -glycoprotein i domain 1 and domain 4/5: ratio of anti
      domain 1 to anti-domain 4/5 as a useful new biomarker for antiphospholipid
      syndrome.
AB  - OBJECTIVE: It has been suggested that only antibodies against domain 1 (D1) of
      beta2 -glycoprotein I (beta2 GPI) are pathogenic and diagnostic. The role of
      antibodies against other beta2 GPI domains is still debated. This study was
      undertaken to evaluate the clinical relevance of domain specificity profiling of
      anti-beta2 GPI IgG antibodies in antiphospholipid syndrome (APS) patients and in
      control groups of patients with systemic autoimmune rheumatic diseases and in
      asymptomatic antiphospholipid antibody (aPL) carriers. METHODS: We evaluated 159
      subjects with persistently positive, medium or high-titer anti-beta2 GPI IgG,
      including 56 patients with thrombotic (obstetric or nonobstetric) primary APS, 31
      women with obstetric primary APS, 42 aPL-positive patients with systemic
      autoimmune rheumatic diseases, and 30 asymptomatic aPL carriers. One hundred
      healthy donors were included. Anti-beta2 GPI D1 and D4/5 IgG were tested on
      research enzyme-linked immunosorbent assays containing recombinant beta2 GPI
      domains. RESULTS: As compared to other groups, aPL carriers displayed higher
      frequency/titer of anti-D4/5 IgG. Unlike anti-D4/5, anti-D1 IgG antibodies were
      more frequent and at higher titer in triple than in single or double aPL-positive
      subjects. An anti-D1 to anti-D4/5 ratio of >=1.5 was predictive of systemic
      autoimmunity (odds ratio 3.25 [95% confidence interval 1.45-7.49], P = 0.005).
      Neither anti-D1 nor anti-D4/5 antibodies were associated with APS clinical
      criteria. CONCLUSION: Anti-D1 IgG is the preferential specificity not only in
      vascular and obstetric primary APS, but also in patients with systemic autoimmune
      rheumatic disease with no clinical features of APS. Conversely, aPL carriers do
      not have a polarized profile toward D1. Combined testing for anti-beta2 GPI IgG
      with different domain specificity allows a more accurate aPL profiling, with
      polarization toward anti-D1 IgG as a possible fingerprint of systemic
      autoimmunity.

PMID- 25939499
TI  - Decoding of visual information from human brain activity: A review of fMRI and
      EEG studies.
AB  - Brain is the command center for the body and contains a lot of information which
      can be extracted by using different non-invasive techniques.
      Electroencephalography (EEG), Magnetoencephalography (MEG) and functional
      magnetic resonance imaging (fMRI) are the most common neuroimaging techniques to
      elicit brain behavior. By using these techniques different activity patterns can
      be measured within the brain to decode the content of mental processes especially
      the visual and auditory content. This paper discusses the models and imaging
      techniques used in visual decoding to investigate the different conditions of
      brain along with recent advancements in brain decoding. This paper concludes that
      it's not possible to extract all the information from the brain, however careful
      experimentation, interpretation and powerful statistical tools can be used with
      the neuroimaging techniques for better results. 

PMID- 25939500
TI  - Does it Matter Whether Canada's Separate Health Technology Assessment Process for
      Cancer Drugs has an Economic Rationale?

PMID- 25939501
TI  - Costs to Health Services and the Patient of Treating Tuberculosis: A Systematic
      Literature Review.
AB  - BACKGROUND: Novel tuberculosis (TB) drugs and the need to treat drug-resistant
      tuberculosis (DR-TB) are likely to bring about substantial transformations in TB
      treatment in coming years. An evidence base for cost and cost-effectiveness
      analyses of these developments is needed. OBJECTIVE: Our objective was to perform
      a review of papers assessing provider-incurred as well as patient-incurred costs
      of treating both drug-susceptible (DS) and multidrug-resistant (MDR)-TB. METHODS:
      Five databases (EMBASE, Medline, the National Health Service Economic Evaluation
      Database, the Cost-Effectiveness Analysis Registry, and Latin American and
      Caribbean Health Services Literature) were searched for cost and economic
      evaluation full-text papers containing primary DS-TB and MDR-TB treatment cost
      data published in peer-reviewed journals between January 1990 and February 2015.
      No language restrictions were set. The search terms were a combination of
      'tuberculosis', 'multidrug-resistant tuberculosis', 'cost', and 'treatment'. In
      the selected papers, study methods and characteristics, quality indicators and
      costs were extracted into summary tables according to pre-defined criteria.
      Results were analysed according to country income groups and for provider costs,
      patient costs and productivity losses. All values were converted to $US, year
      2014 values, so that studies could be compared. RESULTS: We selected 71 treatment
      cost papers on DS-TB only, ten papers on MDR-TB only and nine papers that
      included both DS-TB and MDR-TB. These papers provided evidence on the costs of
      treating DS-TB and MDR-TB in 50 and 16 countries, respectively. In 31 % of the
      papers, only provider costs were included; 26 % included only patient-incurred
      costs, and the remaining 43 % estimated costs incurred by both. From the provider
      perspective, mean DS-TB treatment costs per patient were US$14,659 in high-income
      countries (HICs), US$840 in upper middle-income countries (UMICs), US$273 in
      lower middle-income (LMICs), and US$258 in low-income countries (LICs), showing a
      strong positive correlation. The respective costs for treating MDR-TB were
      US$83,365, US$5284, US$6313 and US$1218. Costs incurred by patients when seeking
      treatment for DS-TB accounted for an additional 3 % of the provider costs in
      HICs. A greater burden was seen in the other income groups, increasing the costs
      of DS-TB treatment by 72 % in UMICs, 60 % in LICs and 31 % in LMICs. When
      provider costs, patient costs and productivity losses were combined, productivity
      losses accounted for 16 % in HICs, 29 % in UMICs, 40 % in LMICs and 38 % in LICs.
      CONCLUSION: Cost data for MDR-TB treatment are limited, and the variation in
      delivery mechanisms, as well as the rapidly evolving diagnosis and treatment
      regimens, means that it is essential to increase the number of studies assessing
      the cost from both provider and patient perspectives. There is substantial
      evidence available on the costs of DS-TB treatment from all regions of the world.
      The patient-incurred costs illustrate that the financial burden of illness is
      relatively greater for patients in poorer countries without universal healthcare
      coverage.

PMID- 25939502
TI  - Transcriptomic profiles of the smoke tree wilt fungus Verticillium dahliae under
      nutrient starvation stresses.
AB  - Verticillium dahliae is a notorious plant pathogen that causes vascular wilt on
      more than 200 plant species. During plant infection, efficient pathogen nutrition
      during the interaction with the host is a requisite for successful infection.
      However, little attention has been focused on nutrient uptake and starvation
      responses in this fungus. Here, we used RNA-Seq to analyze the response of V.
      dahliae to nutrient starvation, including carbon and nitrogen depletion. Gene
      expression profile analysis showed that 1854 genes were differentially expressed
      under carbon starvation (852 upregulated and 539 downregulated genes) and
      nitrogen starvation (487 upregulated and 291 downregulated genes). Among the
      differentially expressed genes, genes involved in utilization or production
      acetyl-CoA, including glycolysis, fatty acid biosynthesis or metabolism, and
      melanin biosynthesis, were repressed under carbon starvation, whereas melanin
      biosynthesis genes were strongly induced under nitrogen starvation. These
      results, combined with VDH1 expression data, suggested that melanin biosynthesis
      and microsclerotia development were induced under nitrogen starvation, but
      microsclerotia development was suppressed under carbon starvation. Furthermore,
      many genes encoding carbohydrate-active enzymes and secreted proteins were
      induced under carbon starvation. Overall, the results improve our understanding
      of the response of V. dahliae to nutrient starvation and help to identify
      potential virulence factors for the development of novel disease control
      strategies. 

PMID- 25939503
TI  - A major locus controlling malondialdehyde content under water stress is
      associated with Fusarium crown rot resistance in wheat.
AB  - Malondialdehyde (MDA) is a naturally occurring product of lipid peroxidation and
      the level of MDA in plant is often used as a parameter to evaluate the damage to
      plants' cells due to stress. Plant with lower amounts of MDA under drought
      conditions is generally considered as more tolerant to drought. In this study, a
      population of recombinant inbred lines was used to map the quantitative trait
      locus (QTLs) that controlled MDA content under well-watered condition (WW) and
      water deficit (WD) condition. A major QTL, designated as Qheb.mda-3B, was
      detected on the long arm of chromosome 3B. Based on interval mapping analysis,
      Qheb.mda-3B explained 31.5 and 39.0 % of the phenotypic variance under WW and WD
      conditions, respectively. Qheb.mda-3B was located in the same interval as a
      previously identified QTL (Qcrs.cpi-3B) that controlled resistance to Fusarium
      crown rot (FCR), a fungal disease caused by Fusarium species. Three pairs of near
      isogenic lines (NILs) previously developed for Qcrs.cpi-3B were found to show
      significant differences in MDA content under WD condition. These results
      suggested that same set of genes is likely to be involved in drought tolerance
      and FCR resistance in wheat. 

PMID- 25939504
TI  - Preventing and reducing the impacts of intimate partner violence: Opportunities
      for Australian ambulance services.
AB  - BACKGROUND: Violence against women is pervasive worldwide, and a high proportion
      of the most damaging violence is perpetrated by male intimate partners. The
      Australian government is committed to action to prevent such violence; however,
      strategies require input and collaboration from all agencies engaging patients,
      including ambulance services. To date no Australian ambulance service has
      published comprehensive guidelines or strategies to improve health outcomes for
      intimate partner violence patients in line with national strategies. OBJECTIVE:
      To propose key actions for Australian ambulance services to undertake to reduce
      the impacts of intimate partner violence in line with national strategies.
      METHODS: We reviewed the Australian government's National Plan to reduce violence
      towards women and its supporting literature, and created key actions for
      Australian ambulance services. RESULTS: Our review has yielded four key actions
      that Australian ambulance services could undertake immediately for the benefit of
      intimate partner violence patients. Actions include collaboration with external
      agencies, education, data collection and championing values promoting zero
      tolerance of violence towards women. CONCLUSIONS: Australian ambulance services
      are currently underserving intimate partner violence patients and must undertake
      immediate action. Successful strategies to address knowledge and policy gaps will
      require significant input and guidance from key organisations, including advocacy
      groups, police and EDs. It is likely that EDs will need to take the lead in
      creating comprehensive policies and guidelines from which ambulance services can
      derive their own policies. Failure to address this practice gap might result in
      paramedics becoming a barrier for intimate partner patients to receive
      appropriate care and support.

PMID- 25939505
TI  - Mutational Analysis of the Chlamydia muridarum Plasticity Zone.
AB  - Pathogenically diverse Chlamydia spp. can have surprisingly similar genomes.
      Chlamydia trachomatis isolates that cause trachoma, sexually transmitted genital
      tract infections (chlamydia), and invasive lymphogranuloma venereum (LGV) and the
      murine strain Chlamydia muridarum share 99% of their gene content. A region of
      high genomic diversity between Chlamydia spp. termed the plasticity zone (PZ) may
      encode niche-specific virulence determinants that dictate pathogenic diversity.
      We hypothesized that PZ genes might mediate the greater virulence and gamma
      interferon (IFN-gamma) resistance of C. muridarum compared to C. trachomatis in
      the murine genital tract. To test this hypothesis, we isolated and characterized
      a series of C. muridarum PZ nonsense mutants. Strains with nonsense mutations in
      chlamydial cytotoxins, guaBA-add, and a phospholipase D homolog developed
      normally in cell culture. Two of the cytotoxin mutants were less cytotoxic than
      the wild type, suggesting that the cytotoxins may be functional. However, none of
      the PZ nonsense mutants exhibited increased IFN-gamma sensitivity in cell culture
      or were profoundly attenuated in a murine genital tract infection model. Our
      results suggest that C. muridarum PZ genes are transcribed--and some may produce
      functional proteins--but are dispensable for infection of the murine genital
      tract.

PMID- 25939506
TI  - CpsA, a LytR-CpsA-Psr Family Protein in Mycobacterium marinum, Is Required for
      Cell Wall Integrity and Virulence.
AB  - LytR-CpsA-Psr family proteins play an important role in bacterial cell wall
      integrity. Although the pathogenic relevance of LytR-CpsA-Psr family proteins has
      been studied in a few bacterial pathogens, their function in mycobacteria remains
      uncharacterized. In this work, a transposon insertion mutant (cpsA::Tn) of
      Mycobacterium marinum was studied. We found that inactivation of CpsA altered
      bacterial colony morphology, sliding motility, cell surface hydrophobicity, and
      cell wall permeability. Besides, the cpsA mutant exhibited a decreased
      arabinogalactan content, indicating that CpsA plays a role in cell wall assembly.
      Moreover, the mutant shows impaired growth within macrophage cell lines and is
      severely attenuated in zebrafish larvae and adult zebrafish. Taken together, our
      results indicated that CpsA, a previously uncharacterized protein, is important
      for mycobacterial cell wall integrity and is required for mycobacterial
      virulence. 

PMID- 25939507
TI  - Comparison of Models for Bubonic Plague Reveals Unique Pathogen Adaptations to
      the Dermis.
AB  - Vector-borne pathogens are inoculated in the skin of mammals, most likely in the
      dermis. Despite this, subcutaneous (s.c.) models of infection are broadly used in
      many fields, including Yersinia pestis pathogenesis. We expand on a previous
      report where we implemented intradermal (i.d.) inoculations to study bacterial
      dissemination during bubonic plague and compare this model with an s.c. MODEL: We
      found that i.d. inoculations result in faster kinetics of infection and that
      bacterial dose influenced mouse survival after i.d. but not s.c. inoculation.
      Moreover, a deletion mutant of rovA, previously shown to be moderately attenuated
      in the s.c. model, was severely attenuated in the i.d. MODEL: Lastly, based on
      previous observations where a population bottleneck from the skin to lymph nodes
      was observed after i.d., but not after s.c., inoculations, we used the latter
      model as a strategy to identify an additional bottleneck in bacterial
      dissemination from lymph nodes to the bloodstream. Our data indicate that the
      more biologically relevant i.d. model of bubonic plague differs significantly
      from the s.c. model in multiple aspects of infection. These findings reveal
      adaptations of Y. pestis to the dermis and how these adaptations can define the
      progression of disease. They also emphasize the importance of using a relevant
      route of infection when addressing host-pathogen interactions.

PMID- 25939508
TI  - Infection of Interleukin 17 Receptor A-Deficient C3H Mice with Borrelia
      burgdorferi Does Not Affect Their Development of Lyme Arthritis and Carditis.
AB  - Recently, a number of studies have reported the presence of interleukin 17 (IL
      17) in patients with Lyme disease, and several murine studies have suggested a
      role for this cytokine in the development of Lyme arthritis. However, the role of
      IL-17 has not been studied using the experimental Lyme borreliosis model of
      infection of C3H mice with Borrelia burgdorferi. In the current study, we
      investigated the role of IL-17 in the development of experimental Lyme
      borreliosis by infecting C3H mice devoid of the common IL-17 receptor A subunit
      (IL-17RA) and thus deficient in most IL-17 signaling. Infection of both C3H and
      C3H IL-17RA(-/-) mice led to the production of high levels of IL-17 in the serum,
      low levels in the heart tissue, and no detectable IL-17 in the joint tissue. The
      development and severity of arthritis and carditis in the C3H IL-17RA(-/-) mice
      were similar to what was seen in wild-type C3H mice. In addition, development of
      antiborrelia antibodies and clearance of spirochetes from tissues were similar
      for the two mouse strains. These results demonstrate a limited role for IL-17
      signaling through IL-17RA in the development of disease following infection of
      C3H mice with B. burgdorferi. 

PMID- 25939509
TI  - Identification of SlpB, a Cytotoxic Protease from Serratia marcescens.
AB  - The Gram-negative bacterium and opportunistic pathogen Serratia marcescens causes
      ocular infections in healthy individuals. Secreted protease activity was
      characterized from 44 ocular clinical isolates, and a higher frequency of
      protease-positive strains was observed among keratitis isolates than among
      conjunctivitis isolates. A positive correlation between protease activity and
      cytotoxicity to human corneal epithelial cells in vitro was determined. Deletion
      of prtS in clinical keratitis isolate K904 reduced, but did not eliminate,
      cytotoxicity and secreted protease production. This indicated that PrtS is
      necessary for full cytotoxicity to ocular cells and implied the existence of
      another secreted protease(s) and cytotoxic factors. Bioinformatic analysis of the
      S. marcescens Db11 genome revealed three additional open reading frames predicted
      to code for serralysin-like proteases noted here as slpB, slpC, and slpD. Induced
      expression of prtS and slpB, but not slpC and slpD, in strain PIC3611 rendered
      the strain cytotoxic to a lung carcinoma cell line; however, only prtS induction
      was sufficient for cytotoxicity to a corneal cell line. Strain K904 with deletion
      of both prtS and slpB genes was defective in secreted protease activity and
      cytotoxicity to human cell lines. PAGE analysis suggests that SlpB is produced at
      lower levels than PrtS. Purified SlpB demonstrated calcium-dependent and AprI
      inhibited protease activity and cytotoxicity to airway and ocular cell lines in
      vitro. Lastly, genetic analysis indicated that the type I secretion system gene,
      lipD, is required for SlpB secretion. These genetic data introduce SlpB as a new
      cytotoxic protease from S. marcescens. 

PMID- 25939510
TI  - Anti-Pneumococcal Capsular Polysaccharide Antibody Response and CD5 B Lymphocyte
      Subsets.
AB  - The role of CD19(+) CD5(+) and CD19(+) CD5(-) B cell subpopulations in the
      antibody response to pneumococcal capsular polysaccharides (caps-PSs) is
      controversial. In the present study, we evaluated the role of human CD19(+)
      CD5(+) and CD19(+) CD5(-) cell populations in the serotype-specific antibody
      response to caps-PS. After vaccination of 5 healthy human adults with Pneumovax
      (23-valent pneumococcal polysaccharide vaccine [PPV23]), IgG anti-caps-PS
      serotype 4 antibody-producing cells resided mainly in the CD19(+) CD5(-) B cell
      subset, as assessed by enzyme-linked immunosorbent spot (ELISpot) analysis.
      Moreover, in a humanized SCID mouse model, CD19(+) CD5(-) B cells were more
      effective than CD19(+) CD5(+) cells in producing IgG anti-cap-PS antibodies.
      Finally, an association was found between the level of IgG anti-caps-PS
      antibodies and the number of CD19(+) CD5(-) B cells in 33 humans vaccinated with
      PPV23. Taken together, our data suggest that CD5 defines a functionally distinct
      population of B cells in humans in the anti-caps-PS immune response. 

PMID- 25939511
TI  - Type 3 Secretion System Island Encoded Proteins Required for Colonization by Non
      O1/non-O139 Serogroup V. cholerae.
AB  - Vibrio cholerae is a genetically diverse species, and pathogenic strains can
      encode different virulence factors that mediate colonization and secretory
      diarrhea. Although the toxin co-regulated pilus (TCP) is the primary colonization
      factor in epidemic causing V. cholerae strains, other strains do not encode TCP
      and instead promote colonization via the activity of a type three secretion
      system (T3SS). Using the infant mouse model and T3SS-positive O39 serogroup
      strain AM-19226, we sought to determine which of 12 previously identified, T3SS
      translocated proteins (Vops) are important for host colonization. We constructed
      in frame deletions in each of the 12 loci in strain AM-19226, and identified five
      Vop deletion strains, including DeltaVopM, which were severely attenuated for
      colonization. Interestingly, a subset of deletion strains was also incompetent
      for effector protein transport. Our collective data therefore suggest that
      several translocated proteins may also function as components of the structural
      apparatus or translocation machinery, and indicate that while VopM is critical
      for establishing an infection, the combined activities of other effectors may
      also contribute to the ability of T3SS-positive strains to colonize host
      epithelial cell surfaces.

PMID- 25939512
TI  - Proteomic Analyses of Intracellular Salmonella enterica Serovar Typhimurium
      Reveal Extensive Bacterial Adaptations to Infected Host Epithelial Cells.
AB  - Salmonella species can gain access into nonphagocytic cells, where the bacterium
      proliferates in a unique membrane-bounded compartment. In order to reveal
      bacterial adaptations to their intracellular niche, here we conducted the first
      comprehensive proteomic survey of Salmonella isolated from infected epithelial
      cells. Among ~ 3,300 identified bacterial proteins, we found that about 100
      proteins were significantly altered at the onset of Salmonella intracellular
      replication. In addition to substantially increased iron-uptake capacities,
      bacterial high-affinity manganese and zinc transporters were also upregulated,
      suggesting an overall limitation of metal ions in host epithelial cells. We also
      found that Salmonella induced multiple phosphate utilization pathways.
      Furthermore, our data suggested upregulation of the two-component PhoPQ system as
      well as of many downstream virulence factors under its regulation. Our survey
      also revealed that intracellular Salmonella has increased needs for certain amino
      acids and biotin. In contrast, Salmonella downregulated glycerol and maltose
      utilization as well as chemotaxis pathways.

PMID- 25939513
TI  - Synergistic Costimulatory Effect of Chlamydia pneumoniae with Carbon
      Nanoparticles on NLRP3 Inflammasome-Mediated Interleukin-1beta Secretion in
      Macrophages.
AB  - The obligate intracellular bacterium Chlamydia pneumoniae is not only a causative
      agent of community-acquired pneumonia but is also associated with a more serious
      chronic disease, asthma, which might be exacerbated by air pollution containing
      carbon nanoparticles. Although a detailed mechanism of exacerbation remains
      unknown, the proinflammatory cytokine interleukin-1beta (IL-1beta) is a critical
      player in the pathogenesis of asthma. C. pneumoniae induces IL-1beta in
      macrophages via NACHT, LRR, and PYD domain-containing protein 3 (NLRP3)
      inflammasome activation and Toll-like receptor 2/4 (TLR2/4) stimulation. Carbon
      nanoparticles, such as carbon nanotubes (CNTs), can also evoke the NLRP3
      inflammasome to trigger IL-1beta secretion from lipopolysaccharide-primed
      macrophages. This study assessed whether costimulation of C. pneumoniae with CNTs
      synergistically enhanced IL-1beta secretion from macrophages, and determined the
      molecular mechanism involved. Enhanced IL-1beta secretion from C. pneumoniae
      infected macrophages by CNTs was dose and time dependent. Transmission electron
      microscopy revealed that C. pneumoniae and CNTs were engulfed concurrently by
      macrophages. Inhibitors of actin polymerization or caspase-1, a component of the
      inflammasome, significantly blocked IL-1beta secretion. Gene silencing using
      small interfering RNA (siRNA) targeting the NLRP3 gene also abolished IL-1beta
      secretion. Other inhibitors (K(+) efflux inhibitor, cathepsin B inhibitor, and
      reactive oxygen species-generating inhibitor) also blocked IL-1beta secretion.
      Taken together, these findings demonstrated that CNTs synergistically enhanced IL
      1beta secretion from C. pneumoniae-infected macrophages via the NLRP3
      inflammasome and caspase-1 activation, providing novel insight into our
      understanding of how C. pneumoniae infection can exacerbate asthma. 

PMID- 25939514
TI  - Replication of a genetic variant for prostate cancer-specific mortality.
AB  - BACKGROUND: Few genetic variants have been confirmed as being associated with
      prostate cancer-specific mortality (PCSM). A recent study identified 22 candidate
      single-nucleotide polymorphisms (SNPs) associated with PCSM in a Seattle-based
      patient cohort. Five of these associations were replicated in an independent
      Swedish cohort. METHODS: We genotyped these 22 SNPs in Physicians' Health Study
      (PHS) participants diagnosed with prostate cancer (PCa). Using the same model
      that was found to be most significant in the Seattle cohort, we examined the
      association of these SNPs with lethal disease with Cox proportional hazards
      models. RESULTS: One SNP, rs5993891 in the ARVCF gene on chromosome 22q11, which
      had also replicated in the Swedish cohort, was also significantly associated with
      PCSM in the PHS cohort (hazard ratio (HR)=0.32; P=0.01). When we tested this SNP
      in an additional cohort (Health Professionals Follow-up Study, HPFS), the
      association was null (HR=0.95, P=0.90); however, a meta-analysis across all
      studies showed a statistically significant association with a HR of 0.52 (0.29
      0.93, P=0.03). CONCLUSIONS: The association of rs5993891 with PCSM was further
      replicated in PHS and remains significant in a meta-analysis, though there was no
      association in HPFS. This SNP may contribute to a genetic panel of SNPs to
      determine at diagnosis whether a patient is more likely to exhibit an indolent or
      aggressive form of PCa. This study also emphasizes the importance of multiple
      rounds of replication.

PMID- 25939515
TI  - The effect of bicycling on PSA levels: a systematic review and meta-analysis.
AB  - BACKGROUND: Recent literature has suggested that bicycling may be associated with
      increases in serum PSA levels, a diagnostic and prognostic marker for prostate
      cancer. To further investigate this relationship, we conducted a systematic
      review and meta-analysis of current literature in this field. METHODS: MEDLINE,
      CENTRAL, CINAHL and SPORTDiscus were searched using MeSH terms and keywords for
      English publications related to bicycle riding and PSA. Studies were included if
      PSA was measured relative to cycling activity in healthy men who were free of any
      prostatic condition. Case studies were excluded. RESULTS: Eight studies met our
      inclusion criteria, comprising 912 participants that engaged in, or self
      reported, bicycling activity. Six studies investigated the acute pre-post change
      in PSA following bicycling activity that ranged from a single cycling bout of 15
      min to a 4-day cycling event. Following cycling activity, two studies reported
      total PSA increased from baseline by up to 3.3-fold, free PSA increased in one
      study by 0.08+/-0.18 ng ml(-)(1) and did not change in four studies. One study
      compared PSA in elite/professional cyclists versus non-cyclists and demonstrated
      no significant difference in PSA measurements between groups. Data from six
      studies were meta-analyzed and demonstrated no significant increase in PSA
      associated with cycling from pre to post (mean change +0.027 ng ml(-)(1),
      s.e.m.=0.08, P=0.74, 95% confidence interval (CI)=-0.17-0.23). CONCLUSIONS: Our
      findings suggest that there is no effect of cycling on PSA; however, the limited
      number of trials and the absence of randomized controlled trials limit the
      interpretation of our results. Additionally, the median sample size only
      consisted of 42 subjects. Therefore, our study may have low statistical power to
      detect a difference in PSA. Although, a higher sample size may demonstrate
      statistical significance, it may not be clinically significant. Studies of higher
      empirical quality are needed.

PMID- 25939516
TI  - Intraprostatic inflammation is positively associated with serum PSA in men with
      PSA <4 ng ml(-1), normal DRE and negative for prostate cancer.
AB  - BACKGROUND: Biopsies performed for elevated serum PSA often show inflammatory
      infiltrates. However, the influence of intraprostatic inflammation on serum PSA
      in men without biopsy indication and negative for prostate cancer has not been
      described in detail. METHODS: We studied 224 men in the placebo arm of the
      Prostate Cancer Prevention Trial (PCPT) who underwent end-of-study biopsy per
      trial protocol, had PSA <4 ng ml(-1), normal digital rectal examination and a
      biopsy negative for cancer. We analyzed data from hematoxylin and eosin-stained
      slides containing a mean of three biopsy cores. Inflammation measures included
      the extent (percentage of tissue area with inflammation) and intensity (product
      of scores for extent and grade) of total, acute and chronic inflammation in the
      entire tissue area examined, and by tissue compartment. We calculated median
      measures of inflammation by prebiopsy serum PSA tertile (>0 to <=0.8, >0.8 to
      <=1.5 and >1.5 to <4.0 ng ml(-1)). We estimated the association between
      percentage of tissue area with inflammation and natural logarithm of PSA using
      linear regression adjusting for age at biopsy. RESULTS: Median percentage of
      tissue area with inflammation increased from 2 to 5 to 9.5% across PSA tertiles
      (P-trend <0.0001). For every 5% increase in tissue area with inflammation, log
      PSA increased by 0.061 ng ml(-1) (P=0.0002). Median extent and intensity scores
      increased across PSA tertiles in luminal and intraepithelial compartments for
      acute inflammation and in stromal and intraepithelial compartments for chronic
      inflammation (all P-trend <=0.05). CONCLUSIONS: In men without clinical suspicion
      of prostate cancer, greater overall inflammation, luminal and intraepithelial
      acute inflammation and stromal and intraepithelial chronic inflammation were
      associated with higher serum PSA.

PMID- 25939517
TI  - Acupuncture relieves symptoms in chronic prostatitis/chronic pelvic pain
      syndrome: a randomized, sham-controlled trial.
AB  - BACKGROUND: There are multiple approaches to the management of chronic
      prostatitis/chronic pelvic pain syndrome (CP/CPPS); and lately the data
      suggesting the ability of acupuncture treatment to decrease pain, positively
      impact quality of life and potentially modulate inflammation has suggested it as
      a potential therapeutic option for men with CP/CPPS. We conducted this study to
      determine whether acupuncture is really an effective therapeutic modality for
      CP/CPPS in terms of >50% decrease in total National Institutes of Health Chronic
      Prostatitis Symptom Index (NIH-CPSI) score from baseline compared with sham.
      METHODS: One hundred patients with CP/CPPS (category III B) in an outpatient
      urology clinic were randomized to receive acupuncture at either seven acupoints
      bilaterally or sham points adjacent to these points. NIH-CPSI was completed by
      each patient before and 6, 8, 16, 24 weeks after the treatment. Mean values of
      total CPSI score and subscores after the treatment and on follow-up following the
      treatment were compared. RESULTS: Of the acupuncture participants, 92% were NIH
      CPSI responders (>50% decrease in total NIH-CPSI score from baseline) compared
      with 48% of sham participants, 8 weeks after the end of the therapy. Both groups
      experienced significant decrease in CPSI subscores throughout the whole follow-up
      period; however, the decline remained significantly greater in the active
      acupuncture group as compared with the sham group. CONCLUSIONS: Our results show
      that the use of acupuncture in treatment of men with CP/CPPS symptoms resulted in
      a significant decrease in total NIH-CPSI scores.

PMID- 25939518
TI  - 30th ASMS Asilomar Conference on Advances in Glycomics and Glycoproteomics:
      Methods and Applications.

PMID- 25939519
TI  - An automated imaging system for radiation biodosimetry.
AB  - We describe here an automated imaging system developed at the Center for High
      Throughput Minimally Invasive Radiation Biodosimetry. The imaging system is built
      around a fast, sensitive sCMOS camera and rapid switchable LED light source. It
      features complete automation of all the steps of the imaging process and contains
      built-in feedback loops to ensure proper operation. The imaging system is
      intended as a back end to the RABiT-a robotic platform for radiation
      biodosimetry. It is intended to automate image acquisition and analysis for four
      biodosimetry assays for which we have developed automated protocols: The
      Cytokinesis Blocked Micronucleus assay, the gamma-H2AX assay, the Dicentric assay
      (using PNA or FISH probes) and the RABiT-BAND assay.

PMID- 25939521
TI  - SPARTAN annual meeting, New York City 2014.

PMID- 25939520
TI  - Biomarkers for diagnosis, monitoring of progression, and treatment responses in
      ankylosing spondylitis and axial spondyloarthritis.
AB  - With the growing awareness of the impact of chronic back pain and axial
      spondyloarthritis and recent breakthroughs in genetics and the development of
      novel treatments which may impact best on early disease, the need for markers
      that can facilitate early diagnosis and profiling those individuals at the
      highest risk for a bad outcome has never been greater. The genetic basis of
      ankylosing spondylitis has been considerably advanced, and HLA-B27 testing has a
      role in the diagnosis. Knowledge is still incomplete of the rest of the genetic
      contribution to disease susceptibility, and it is likely premature to use
      extensive genetic testing (other than HLA-B27) for diagnosis. Serum and plasma
      biomarkers have been examined extensively in assessing disease activity,
      treatment response, and as predictors or radiographic severity. For assessing
      disease activity, other than C-reactive protein and erythrocyte sedimentation
      rate, the most work has been in examining cytokines (particularly interleukin 17
      and 23), matrix metalloproteinase (MMP) markers (particularly MMP3). For
      assessing those at the highest risk for radiographic progression, biomarkers of
      bony metabolism, cartilage and connective tissue degradation products, and
      adipokines have been most extensively assessed. The problem is that no individual
      biomarkers has been reproducibly shown to assess disease activity or predict
      outcome, and this area still remains an unmet need, of relevance to industry
      stakeholders, to regulatory bodies, to the healthcare system, to academic
      investigators, and finally to patients and providers. 

PMID- 25939522
TI  - Role of IL-17 in the pathogenesis of psoriatic arthritis and axial
      spondyloarthritis.
AB  - Th17 cells are a discrete subset of T cell subpopulation, which produce IL-17 and
      certain other pro-inflammatory cytokines. A regulatory role of Th17 cells have
      been proposed in several autoimmune diseases including psoriasis, psoriatic
      arthritis (PsA), ankylosing spondylitis (AS), rheumatoid arthritis, inflammatory
      bowel disease, systemic lupus erythematosus, and multiple sclerosis. Psoriatic
      disease is an autoimmune disease which mainly involves skin and joints. Until
      recently, psoriasis and PsA were thought to be Th1 mediated disease, but after
      the discovery of IL-17 and IL-17 knockout animal studies as well as human
      experimental data indicate a crucial role of the Th17 cells in the pathogenesis
      of psoriasis and PsA. Our research group have not only found abundance of
      CD4(+)IL-17(+) T cells, mainly the memory phenotype (CD4RO(+)CD45RA(-)CD11a(+))
      in the synovial fluid, but also have shown the existence of a functional IL-17
      receptor in synovial fibroblast of psoriatic arthritis patients. Similarly, both
      animal and human studies indicate a regulatory role of the Th17 cells in AS; most
      critical observations are that Th17 cytokines (IL-17 and IL-22) can contribute to
      bone erosion, osteitis and new bone formation the hall mark skeletal features
      associated with the pathophysiology of AS. In this review article, we have
      discussed the contributing role of the IL-23/IL-17 axis in the pathogenesis of
      PsA and AS. 

PMID- 25939523
TI  - Tumor necrosis factor-alpha antagonist therapy for concomitant rheumatoid
      arthritis and hepatitis C virus infection: a case series study.
AB  - The aim of this study was to investigate treatment response and hepatic safety of
      anti-tumor necrosis factor-alpha therapy among patients with concomitant
      rheumatoid arthritis (RA) and hepatitis C virus (HCV) infection. We reviewed the
      charts of 101 consecutive RA patients who were eligible for anti-TNF-alpha
      therapy in the Chiayi Branch of Chang Gung Memorial Hospital. Group A patients
      were sero-positive for anti-HCV antibodies and had HCV RNA but were negative for
      hepatitis B surface antigen (HBsAg). Group B (the control group) patients were
      sero-negative for both anti-HCV antibodies and HBsAg. Response to anti-TNF-alpha
      treatment was assessed by calculating disease activity score at 28 joints (DAS28)
      at baseline and 5, 8, and 11 months after the start of TNF-alpha antagonist
      therapy. Percentage change in DAS28 from baseline to month 5 was 21.36 +/- 8.01 %
      in group A and 26.98 +/- 10.43 % in group B (p = 0.011). However, there was no
      obvious difference in treatment response between groups at other time points.
      Anti-TNF-alpha therapy was discontinued within 1 year of starting treatment in
      two subjects in group A and 4 in group B. Response to anti-TNF-alpha was better
      in group B than in group A at 5 months, but there was no substantial difference
      in response at the 1-year evaluation. Although the study sample was small, our
      results suggest that the safety of anti-TNF-alpha therapy is similar in RA
      patients with and without concomitant HCV infection.

PMID- 25939524
TI  - Reliability and validity of the Advanced Basal Cell Carcinoma Index (aBCCdex).
AB  - BACKGROUND: Patient-reported outcome (PRO) questionnaires were recently developed
      specifically for use with patients with advanced basal cell carcinoma (aBCC) and
      basal cell carcinoma naevus syndrome (BCCNS). OBJECTIVES: To evaluate the
      measurement properties of PRO questionnaires for use in patients with aBCC or
      BCCNS. METHODS: In total 129 patients from 10 clinical sites in the U.S.A. and
      the BCCNS Support Network completed the two newly developed questionnaires
      multiple times over 3 months. Patients also completed the Skindex-16 and the 12
      Item Short-Form Health Survey as collateral measures. Psychometric properties of
      the questionnaires were evaluated, including internal consistency and test-retest
      reliability, construct and known-groups validity, and responsiveness. RESULTS:
      Based on the results of exploratory factor analysis and clinical input, the two
      newly developed questionnaires were combined into a single questionnaire, called
      the aBCCdex, which is relevant for patients with both aBCC and BCCNS. The
      internal consistency reliability was acceptable, and all aBCCdex scale scores
      correlated significantly with conceptually similar scales. When divided into
      groups that differed based on scores from collateral measures, aBCCdex scale
      scores differentiated between groups (known-groups validity) and were responsive
      to change. CONCLUSIONS: The aBCCdex is a brief and comprehensive questionnaire
      appropriate for use with patients with aBCC and BCCNS. Its reliability and
      validity have been confirmed. Further research is necessary to estimate the
      minimally important difference in a larger patient population.

PMID- 25939525
TI  - Women's right to health and Ireland's abortion laws.
AB  - The provision of the Irish Constitution that guarantees "the unborn" a right to
      life equal to that of a pregnant woman has consequences for access to abortion
      and the care of women in pregnancy generally. Long-awaited legislation to give
      effect to the narrow constitutional right to abortion was enacted into law in
      2013. In 2014, a guidance document for health professionals' implementation of
      the legislation was published. However, the legislation and guidance document
      fall far short of international human rights bodies' recommendations: they fail
      to deliver effective procedural rights to all of the women eligible for lawful
      abortion within the state and create new legal barriers to women's reproductive
      rights. At the same time, cases continue to highlight that the Irish Constitution
      imposes an unethical and rights-violating legal regime in non-abortion-related
      contexts. Recent developments suggest that both the failure to put guidelines in
      place and the development of guidelines that are not centered on women or based
      on rights further reduce women's access to rights and set unacceptable
      limitations on women's reproductive autonomy. Nevertheless, public and
      parliamentary scrutiny of cases involving Ireland's abortion laws is increasingly
      focusing on the need for reform. 

PMID- 25939526
TI  - [The long road to an effective treatment of acute cerebral ischemia].

PMID- 25939527
TI  - Extensive pneumatized air cells causing susceptibility artifacts in the petrosus
      part of the ICA.
AB  - INTRODUCTION: 3D-Time-of-flight magnetic-resonance-angiography (TOF MRA) is an
      established method in vessel analysis. However, many artifacts that occur may
      lead to a false diagnosis. This retrospective study evaluates the coherence of MR
      artifacts to extensive pneumatized air cells surrounding the internal carotid
      artery (ICA) in the petrosus part of the temporal bone. MATERIALS AND METHODS:
      Patients who received 3D-TOF MRA and multidetector helical computed tomography
      (CT) angiography were registered from April 2012 to April 2013. Of these
      patients, both ICAs in the petrosus part were analyzed. Vertical maximum
      intensity projection (MIP) artifacts were graduated as normal, mild to moderate,
      and severe artifacts. The distinction of the vertical part of the pneumatized air
      cells was also categorized in three groups, regarding the circumference of the
      ICA in pneumatization <= 90 degrees , between 90 degrees  and 180 degrees , and
      >= 180 degrees . RESULTS: A total of 203 vessels were collected for analysis. The
      more extensive the pneumatized air cells were present, the more band-like
      artifacts and pseudostenosis at the vertical portion of the petrosus part of the
      ICA were registered. CONCLUSION: Careful examination of the source images and
      evaluation of the size of the pneumatized air cells with CT scan are essential to
      avoid false positive diagnosis in the distal petrosus part of the ICA.

PMID- 25939529
TI  - Corporeal reflexivity and autism.
AB  - Ethnographic video recordings of high functioning children with autism or
      Aspergers Syndrome in everyday social encounters evidence their first person
      perspectives. High quality visual and audio data allow detailed analysis of
      children's bodies and talk as loci of reflexivity. Corporeal reflexivity involves
      displays of awareness of one's body as an experiencing subject and a physical
      object accessible to the gaze of others. Gaze, demeanor, actions, and sotto voce
      commentaries on unfolding situations indicate a range of moment-by-moment
      reflexive responses to social situations. Autism is associated with
      neurologically based motor problems (e.g. delayed action-goal coordination,
      clumsiness) and highly repetitive movements to self-soothe. These behaviors can
      provoke derision among classmates at school. Focusing on a 9-year-old girl's
      encounters with peers on the playground, this study documents precisely how
      autistic children can become enmeshed as unwitting objects of stigma and how they
      reflect upon their social rejection as it transpires. Children with autism
      spectrum disorders in laboratory settings manifest diminished understandings of
      social emotions such as embarrassment, as part of a more general impairment in
      social perspective-taking. Video ethnography, however, takes us further, into
      discovering autistic children's subjective sense of vulnerability to the gaze of
      classmates. 

PMID- 25939528
TI  - Timing of Mean Transit Time Maximization is Associated with Neurological Outcome
      After Subarachnoid Hemorrhage.
AB  - PURPOSE: Computed tomography perfusion (CTP) has gained significant relevance for
      the radiological screening of patients at risk of developing delayed cerebral
      ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Particularly, the
      impact of MTTPEAK, i.e., the maximal mean transit time value in a series of CTP
      measurements, for the prediction of long-term outcome has recently been
      demonstrated by our group. Complementing this recent work, the present study
      investigated how the timing of MTTPEAK affected the long-term outcome after
      aneurysmal subarachnoid hemorrhage. METHODS: CTP examinations from 103 patients
      with clinical deterioration attributed to DCI after aSAH were retrospectively
      analyzed for time interval between SAH ictus and onset of MTTPEAK in association
      with modified Rankin Scale (mRS) 23.1 months after SAH. RESULTS: Patients with
      unfavorable outcome (mRS > = 2) suffered significant earlier MTTPEAK onsets than
      patients with favorable outcome (mRS = 0 and 1). MTTPEAK within the first week
      was associated with significantly higher mRS scores compared to later MTTPEAK.
      Timing of MTTPEAK together with the value of MTTPEAK and initial World Federation
      of Neurosurgical Societies (WFNS) grade was a significant predictor for an
      unfavorable outcome (mRS > = 2). CONCLUSIONS: The current findings suggest a
      presumably higher vulnerability of the brain to early microcirculatory
      impairments after aSAH and highlight that timing of MTT elevations could be
      considered for the identification of patients at increased risk for poor
      neurological outcome due to DCI.

PMID- 25939530
TI  - The Idiographic Approach in Psychological Research. The Challenge of Overcoming
      Old Distinctions Without Risking to Homogenize.
AB  - In this paper I discuss the relevance of the single-case approach in
      psychological research. Based upon work by Hurtado-Parrado and Lopez-Lopez
      (Integrative Psychological and Behavioral Science, 2015), who outlined the
      possibility that Single-Case Methods (SCMs) could be a valid alternative to Null
      Hypothesis Significance Testing (NHST), I introduce the idiographic approach
      (Salvatore and Valsiner Theory & Psychology, 20(6), 817-833, 2010; Valsiner
      Cultural & Psychology, 20(2), 147-159, 2014; Salvatore Culture & Psychology,
      20(4), 477-500, 2014) based on the logic of abductive generalization, rather than
      the logic of inductive generalization. I present the theoretical, epistemological
      and methodological assumptions that this approach proposes; in particular, I
      discuss the re-conceptualization of some now obsolete rigid opposition, the
      inconsistency of sample use in psychological research, the relationship between
      uniqueness and general, the relationship between theory and phenomena, and
      finally the validation process. 

PMID- 25939532
TI  - Interleukin-22 upregulates HB-EGF expression in HaCaT cells via JAK2/STAT3 and
      ERK1/2 signalling.

PMID- 25939531
TI  - Therapeutic opportunities to prevent post-traumatic arthritis: Lessons from the
      natural history of arthritis after articular fracture.
AB  - An estimated 12% of patients seeking surgical intervention for symptomatic
      arthritis have an etiology of post-traumatic arthritis (PTA). The onset of PTA is
      rapid in the setting of articular fracture (AF). The investigation began with
      development of a murine model of a closed AF that develops PTA. In the process of
      characterizing this model a technique was developed for assessing quantitative
      synovial fluid biomarker concentrations. The work began with observations of the
      natural history of PTA development in the C57BL/6 strain of mice. A species of
      mice (MRL/MpJ) was found that is protected from PTA after AF. Further work
      identified key differences between mouse strains that did and did not develop
      PTA. This knowledge led to an intervention based on anti-cytokine (interleukin 1
      receptor antagonist, (IL-1Ra) delivery in the C57BL/6 strain of mice that
      successfully prevented PTA following AF. This success in preventing PTA in the
      murine model has elucidated several important clinical implications: 1) Pro
      inflammatory cytokines play an important role in the development of PTA after
      joint injury, 2) Pharmacologic intervention can lessen the severity of PTA after
      an AF, and 3) The murine AF model of joint injury provides a novel means of
      studying mechanisms of PTA development.

PMID- 25939533
TI  - Repeated, high-dose dextromethorphan treatment decreases neurogenesis and results
      in depression-like behavior in rats.
AB  - Abuse of cough mixture is increasingly prevalent worldwide. Clinical studies
      showed that chronic consumption of cough mixture at high dosages may lead to
      psychiatric symptoms, especially affective disturbances, with the underlying
      mechanisms remain elusive. The present study aims at exploring the effect of
      repeated, high-dose dextromethorphan (DXM, a common active component of cough
      mixture) treatment on adult hippocampal neurogenesis, which is associated with
      pathophysiology of mood disturbances. After treatment with a high-dose of DXM (40
      mg/kg/day) for 2 weeks, Sprague-Dawley rats showed increased depression-like
      behavior when compared to the control animals. Neurogenesis in the hippocampus
      was suppressed by DXM treatment, which was indicated by decreases in number of
      proliferative cells and doublecortin (an immature neuron marker)-positive new
      neurons. Furthermore, the dendritic complexity of the immature neurons was
      suppressed by DXM treatment. These findings suggest that DXM induces depression-
      and anxiety-like behavior and suppresses neurogenesis in rats. The current
      experimental paradigm may serve as an animal model for study on affective effect
      of cough mixture abuse, rehabilitation treatment options for abusers and the
      related neurological mechanisms.

PMID- 25939534
TI  - Sinomenine potentiates degranulation of RBL-2H3 basophils via up-regulation of
      phospholipase A2 phosphorylation by Annexin A1 cleavage and ERK phosphorylation
      without influencing on calcium mobilization.
AB  - Sinomenine (SIN), an alkaloid derived from the Chinese medicinal plant Sinomenium
      acutum, is the major component of Zhengqing Fongtong Ning (ZQFTN), a
      pharmaceutical drug produced by Hunan Zhengqing Pharmaceutical Co. Ltd. in China
      for the treatment of rheumatoid arthritis and other autoimmune diseases. Some
      clinic reports indicate that ZQFTN may induce an anaphylactic reaction via
      potentiating the degranulation of immune cells. In the current study, we aimed to
      examine whether SIN is capable of inducing the degranulation of basophilic
      leukemia 2H3 (RBL-2H3) cells to elucidate how the anaphylactic reaction occurs.
      The results revealed that SIN could up-regulate beta-hexosaminidase levels in RBL
      2H3 cells without significant cytotoxicity, suggesting that SIN could induce the
      degranulation of RBL-2H3 cells. Furthermore, SIN increased the release of
      prostaglandin D2 (PGD2) and prostaglandin E2 (PGE2) in RBL-2H3 cells via
      promoting the expression of phosphorylated-extracellular signal-regulated kinase
      (P-ERK), the cleavage of Annexin A1 (ANXA1), and phosphorylated-cytosolic
      phospholipase A2 (P-cPLA2), as well as cyclooxygenase-2 (COX-2). The ERK
      inhibitor, PD98059, significantly attenuated the up-regulatory effect of SIN on
      cPLA2 phosphorylation. Interestingly, SIN did not significantly increase Ca(2+)
      influx in the cells. These findings not only explored the anaphylactic reaction
      and underlying mechanism of ZQFTN in RBL-2H3 cells, but may promote the
      development of relevant strategies for overcoming the adverse effects of the
      drug. 

PMID- 25939535
TI  - Brazilin plays an anti-inflammatory role with regulating Toll-like receptor 2 and
      TLR 2 downstream pathways in Staphylococcus aureus-induced mastitis in mice.
AB  - Mastitis, which commonly occurs during the postpartum period, is caused by the
      infection of the mammary glands. The most common infectious bacterial pathogen of
      mastitis is Staphylococcus aureus (S. aureus) in both human and animals.
      Brazilin, a compound isolated from the traditional herbal medicine Caesalpinia
      sappan L., has been shown to exhibit multiple biological properties. The present
      study was performed to determine the effect of brazilin on the inflammatory
      response in the mouse model of S. aureus mastitis and to confirm the mechanism of
      action involved. Brazilin treatment was applied in both a mouse model and cells.
      After brazilin treatment of cells, Western blotting and qPCR were performed to
      detect the protein levels and mRNA levels, respectively. Brazilin treatment
      significantly attenuated inflammatory cell infiltration and inhibited the
      expressions of TNF-alpha, IL-1beta and IL-6 in a dose-dependent manner.
      Administration of brazilin in mice suppressed S. aureus-induced inflammatory
      injury and the production of proinflammatory mediators. This suppression was
      achieved by reducing the increased expression of TLR2 and regulating the NF
      kappaB and MAPK signaling pathways in the mammary gland tissues and cells with S.
      aureus-induced mastitis. These results suggest that brazilin appears to be an
      effective drug for the treatment of mastitis and may be applied as a clinical
      therapy. 

PMID- 25939536
TI  - Inhibition of respiratory syncytial virus replication and virus-induced p38
      kinase activity by berberine.
AB  - Respiratory syncytial virus (RSV) causes severe lower respiratory tract infection
      and poses a major public health threat worldwide. No effective vaccines or
      therapeutics are currently available; berberine, an isoquinoline alkaloid from
      various medicinal plants, has been shown to exert antiviral and several other
      biological effects. Recent studies have shown that p38 mitogen-activated protein
      kinase (MAPK) activity is implicated in infection by and replication of viruses
      such as RSV and the influenza virus. Because berberine has previously been
      implicated in modulating the activity of p38 MAPK, its effects on RSV infection
      and RSV-mediated p38 MAPK activation were examined. Replication of RSV in
      epithelial cells was significantly reduced by treatment with berberine. Berberine
      treatment caused decrease in viral protein and mRNA syntheses. Similar to
      previously reported findings, RSV infection caused phosphorylation of p38 MAPK at
      a very early time point of infection, and phosphorylation was dramatically
      reduced by berberine treatment. In addition, production of interleukin-6 mRNA
      upon RSV infection was significantly suppressed by treatment with berberine,
      suggesting the anti-inflammatory role of berberine during RSV infection. Taken
      together, we showed that berberine, a natural compound already proven to be safe
      for human consumption, suppresses the replication of RSV. In addition, the
      current study suggests that inhibition of RSV-mediated early p38 MAPK activation,
      which has been implicated as an early step in viral infection, as a potential
      molecular mechanism. 

PMID- 25939537
TI  - Utility of Ara h 2 sIgE levels to predict peanut allergy in Canadian children.

PMID- 25939538
TI  - Loss of AQP3 protein expression is associated with worse progression-free and
      cancer-specific survival in patients with muscle-invasive bladder cancer.
AB  - PURPOSE: Urothelial carcinoma has recently been shown to express several
      aquaporins (AQP), with AQP3 being of particular interest as its expression is
      reduced or lost in tumours of higher grade and stage. Loss of AQP3 expression was
      associated with worse progression-free survival (PFS) in patients with pT1
      bladder cancer. The objective of this study was to investigate the prognostic
      value of AQP3 expression in patients with muscle-invasive bladder carcinoma
      (MIBC). METHODS: Retrospective single-centre analysis of the oncological outcome
      of patients following radical cystectomy (Cx) due to MIBC. Immunohistochemistry
      was used to assess AQP3 protein expression in 100 Cx specimens. Expression levels
      of AQP3 were related to clinicopathological variables. The impact of biomarker
      expression on progression-free, cancer-specific and overall survival was
      determined by multivariate Cox regression analysis (MVA). RESULTS: High
      expression of AQP3 by the tumour was associated with a statistically
      significantly improved PFS (75 vs. 19 %, p = 0.043) and CSS (75 vs. 18 %, p =
      0.030) and, alongside lymph node involvement, was an independent predictor of PFS
      (HR 2.871, CI 1.066-7.733, p = 0.037), CSS (HR 3.325, CI 1.204-8.774, p = 0.019)
      and OS (HR 2.001, CI 1.014-3.947) in MVA. CONCLUSIONS: Although the results of
      the study would be strengthened by a larger, more appropriately powered,
      prospective, multi-institutional study, our findings strongly suggest that AQP3
      expression status may represent an independent predictor of PFS and CSS in MIBC
      and may help select patients in need for (neo-)adjuvant chemotherapy.

PMID- 25939539
TI  - Positive surgical margins after radical prostatectomy: What should we care about?
AB  - PURPOSE: Positive surgical margins (PSMs) after radical prostatectomy (RP) are a
      known factor associated with biochemical recurrence (BCR) and raise the issue of
      adjuvant treatment by radiotherapy versus salvage treatment at recurrence. To
      help this choice, our study aimed to analyze BCR-free survival and factors
      associated with BCR in patients with PSM and undetectable postoperative prostate
      specific antigen (PSA). METHODS: Between 2005 and 2008, 630 patients had RP for
      localized prostate cancer in our center. We included patients with PSM, uninvaded
      nods, undetectable postoperative PSA and no adjuvant treatment. The 5-year BCR
      free survival was calculated using Kaplan-Meier method. Logistic regression
      models were used to determine the factors associated with BCR in univariate and
      multivariate analyses (Cox model). RESULTS: The PSM rate was 32.7 % (n = 206
      patients), and 110 patients corresponded to the inclusion criteria. The median
      follow-up was 72 months. The BCR rate was 30 % with a 5-year BCR-free survival of
      83.9 %. The factors significantly associated with BCR were preoperative PSA,
      predominance and percentage of Gleason 4, tumor volume, PSM length and
      predominance of Gleason 4 at the margin. In the multivariate analysis, the
      remaining two significant factors were PSM length [OR 4.35, 95 % CI (1.011
      1.421), p = 0.037] and tumor volume [OR 4.29, 95 % CI (1.011-1.483), p = 0.038].
      CONCLUSION: Over a 5-year follow-up, only one-third of patients experienced BCR.
      It might be reasonable to postpone adjuvant radiotherapy for patients with PSM
      and undetectable PSA after RP. Tumor volume and PSM length were associated with
      BCR and should be taken into account in the postoperative treatment management.

PMID- 25939541
TI  - Nucleoside-Nucleotide Analog Combination Therapy Is Effective in Preventing
      Recurrent Hepatitis B After Liver Transplantation.
AB  - BACKGROUND: Hepatitis B immune globulin (HBIg) in combination with a
      nucleos(t)ide analog is the mainstay of prophylactic regimen to prevent
      recurrence of hepatitis B following orthotopic liver transplantation (OLT). HBIg
      therapy is costly and inconvenient for the patients. There is a growing
      experience converting HBIg/nucleos(t)ide to combination nucleotide/nucleoside
      analogs from. METHODS: Twenty-six patients that underwent OLT between March 2001
      and July 2011 who had received at least 12 months of HBIg and single
      nucleos(t)ide were enrolled. HBsAg and HBV DNA were undetectable, and anti-HBs
      were detectable at the time of switch. HBV DNA and HBsAg were measured every 3
      months following discontinuation of HBIg and addition of nucleos(t)ide. RESULTS:
      Patients included 23 Asians/3 Caucasian, 21 males/5 females. Mean time of
      conversion from HBIg/nucleos(t)ide to nucleoside/nucleotide combination was 77.5
      (range 11-132) months after OLT. Mean duration of follow-up after conversion was
      31.9 (range 14-70) months. All patients had undetectable HBV DNA, and 24 patients
      remained HBsAg negative during follow-up. Two patients recurred 7 and 9 months
      later, respectively, with detectable HBsAg. Both patients continued to have
      undetectable HBV DNA and normal ALT. HBsAg was neutralized by reinfusion of HBIg.
      CONCLUSION: Nucleoside/nucleotide combination is an effective alternative to
      HBIg/nucleos(t)ide to prevent recurrence of hepatitis B after OLT.

PMID- 25939540
TI  - Role of genetic and molecular profiling in sarcomas.
AB  - OPINION STATEMENT: The treatment of sarcomas has been challenging due to their
      heterogeneity, rarity in the general population, relative insensitivity to
      chemotherapeutics, and lack of effective targeted agents. One of the first major
      breakthroughs in the treatment of sarcomas was the use of imatinib to treat
      gastrointestinal stromal tumors (GISTs). Since then, advanced molecular
      techniques and genetic profiling have revolutionized the approach to sarcoma
      classification, diagnosis, prognosis and, most importantly, treatment. As the
      sarcoma genetic database continues to expand, the basis for how we classify,
      diagnose, and treat these challenging malignancies will be redefined. The overall
      goal of these types of techniques has been to determine a molecular blueprint for
      each sarcoma subtype and discover actionable alterations that lend themselves to
      targeted therapies. Other important information derived from these large genomic
      databases includes biomarkers, prognostic indicators, and information regarding
      tumorigenesis. Eventually, advanced molecular techniques will provide a
      personalized-medicine approach that tailors each treatment regimen to the
      patient's own tumor genome.

PMID- 25939542
TI  - Small Intestinal Multifocal Stenosing Ulceration.

PMID- 25939543
TI  - Gastroenterologists' Views of Shared Decision Making for Patients with
      Inflammatory Bowel Disease.
AB  - BACKGROUND: There is limited information on gastroenterologists' perspectives of
      shared decision making (SDM) in discussions of therapeutic agents with
      inflammatory bowel disease (IBD) patients. AIMS: To examine gastroenterologists'
      perspectives about SDM with IBD patients, using a novel statistical hybrid
      approach to analyze qualitative data. METHODS: Physician interviews and online
      surveys were conducted from a panel of gastroenterologists in April 2012.
      Gastroenterologists were asked about their barriers to SDM, SDM practices,
      relationship to their patients, knowledge of SDM, and insights into SDM
      implementation. Key audio excerpts adapted from the interviews were used for
      moment-to-moment affect trace analysis in an online survey. Cluster analysis was
      used to segment gastroenterologists into mutually exclusive provider groups.
      RESULTS: One hundred and six gastroenterologists completed the survey (88 % male;
      55 % <= 50 years of age). Over three-fourths of gastroenterologists were familiar
      with SDM (77 %). The vast majority of gastroenterologists (80 %) tried to use a
      form of SDM with their patients; only 12 % stated that they have a systematic,
      consistent, and formally documented approach to SDM. Three unique physician
      clusters were identified: SDM Believers (20 %, n = 20); SDM Skeptics (47 %, n =
      47); and SDM Enthusiasts (34 %, n = 34). The three key barriers to practicing SDM
      were lack of the following: time (74 %), reimbursement (70 %), and tools (51 %).
      Twenty-two percent of gastroenterologists do not currently use SDM tools.
      CONCLUSIONS: Gastroenterologists lack the systematic approaches and tools for
      implementing SDM within their IBD practices. These data offer a foundation for
      future research in developing and testing SDM programs for gastroenterologists
      and their IBD patients.

PMID- 25939545
TI  - Investigating cognitive transfer within the framework of music practice: genetic
      pleiotropy rather than causality.
AB  - The idea of far transfer effects in the cognitive sciences has received much
      attention in recent years. One domain where far transfer effects have frequently
      been reported is music education, with the prevailing idea that music practice
      entails an increase in cognitive ability (IQ). While cross-sectional studies
      consistently find significant associations between music practice and IQ,
      randomized controlled trials, however, report mixed results. An alternative to
      the hypothesis of cognitive transfer effects is that some underlying factors,
      such as shared genes, influence practice behaviour and IQ causing associations on
      the phenotypic level. Here we explored the hypothesis of far transfer within the
      framework of music practice. A co-twin control design combined with classical
      twin-modelling based on a sample of more than 10,500 twins was used to explore
      causal associations between music practice and IQ as well as underlying genetic
      and environmental influences. As expected, phenotypic associations were moderate
      (r = 0.11 and r = 0.10 for males and females, respectively). However, the
      relationship disappeared when controlling for genetic and shared environmental
      influences using the co-twin control method, indicating that a highly practiced
      twin did not have higher IQ than the untrained co-twin. In line with that
      finding, the relationship between practice and IQ was mostly due to shared
      genetic influences. Findings strongly suggest that associations between music
      practice and IQ in the general population are non-causal in nature. The
      implications of the present findings for research on plasticity, modularity, and
      transfer are discussed. 

PMID- 25939544
TI  - Lymph Node Ratio as an Alternative to the Number of Metastatic Lymph Nodes for
      the Prediction of Esophageal Carcinoma Patient Survival.
AB  - BACKGROUND: The prognostic value of metastatic lymph node ratio (LNR) is still
      controversial in esophageal cancer. AIM: This study aimed to compare the impact
      of AJCC N staging system (pN) and LNR on the prediction of long-term survival of
      patients with esophageal carcinoma. METHODS: A total of 496 patients were
      retrospectively analyzed who underwent esophageal resection at Henan Tumor
      Hospital from January 2006 to December 2010. The Kaplan-Meier method and log-rank
      test were used to estimate survival curves. Univariate and multivariate analyses
      were performed to compare prognostic factors for long-term survival. The
      difference between pN and LNR with overall survival (OS) was compared by receiver
      operating characteristic (ROC) curve and area under the curve (AUC). RESULTS: The
      1-, 3-, 5-year overall survival rates of 496 patients were 73.6, 47.1 and 34.2 %,
      respectively. Univariate analyses showed that diseased region, tumor length,
      depth of tumor invasion, pN and LNR affected the prognosis, and multivariate
      analyses demonstrated that depth of tumor invasion, pN and LNR were independent
      risk factors. Among the three significant variables verified by multivariate
      analyses, LNR was the best for inadequately staged patients (<12 examined LNs).
      ROC analyses showed that compared with pN (AUC = 0.579, p = 0.037), LNR (AUC =
      0.680, p = 0.002) had better predictive value (z = 2.275, p = 0.029).
      CONCLUSIONS: LNR has greater prognostic value than pN for esophageal squamous
      cell carcinoma, especially for patients with <12 LNs removed.

PMID- 25939546
TI  - Challenges during long-term follow-up of ICU patients with and without chronic
      disease.
AB  - INTRODUCTION: Reflecting on researchers' experiences during follow-up of patients
      enrolled in research may lead to improved understanding of the challenges faced
      in maintaining contact when patients leave hospital. AIMS: (1) Describe the
      challenges researchers face when following-up patients who survive ICU. (2)
      Identify issues that influenced our ability to follow-up patients. METHODS: This
      sub-study was part of a larger "case-control" study investigating the quality of
      life of ICU survivors with and without pre-existing chronic disease. Patients
      completed self-assessment QLQ and symptom assessment before hospital discharge
      and at six months, plus they were asked to keep a paper diary of healthcare
      services used. Patient contact was maintained by monthly telephone calls. Each
      telephone call was logged and summaries of conversations documented. Our
      experience of conducting the study was reviewed by the identification of common
      issues which arose from the follow-up of patients. RESULTS: Thirty patients with
      a history of chronic disease and 30 patients without underlying chronic disease
      were followed-up. A total of 582 telephone calls were made for 60 patients
      discharged from hospital of which 261 (45%) calls led to a telephone interview.
      Only 19 (30%) of diaries were completed and returned. We identified six
      challenges associated with issues that arose from the follow-up of patients.
      CONCLUSION: We underestimated the number of telephone calls required for follow
      up after discharge. Diaries were unreliable sources of data suggesting strategies
      are needed to improve compliance. How patients respond to follow-up is not always
      predictable. Processes are needed to deal with unexpected information provided
      during telephone follow-up.

PMID- 25939547
TI  - Patient participation in pulmonary interventions to reduce postoperative
      pulmonary complications following cardiac surgery.
AB  - BACKGROUND: Clinical interventions aimed at reducing the incidence of
      postoperative pulmonary complications necessitate patient engagement and
      participation in care. Patients' ability and willingness to participate in care
      to reduce postoperative complications is unclear. Further, nurses' facilitation
      of patient participation in pulmonary interventions has not been explored.
      OBJECTIVE: To explore patients' ability and willingness to participate in
      pulmonary interventions and nurses' facilitation of pulmonary interventions.
      DESIGN: Single institution, case study design. Multiple methods of data
      collection were used including preadmission (n=130) and pre-discharge (n=98)
      patient interviews, naturalistic observations (n=48) and nursing focus group
      interviews (n=2). SETTING: A cardiac surgical ward of a major metropolitan,
      tertiary referral hospital in Melbourne, Australia. PARTICIPANTS: One hundred and
      thirty patients admitted for cardiac surgery via the preadmission clinic during a
      1-year period and 40 registered nurses who were part of the permanent workforce
      on the cardiac surgical ward. OUTCOME MEASURES: Patients' understanding of their
      role in pulmonary interventions and patients' preference for and reported
      involvement in pulmonary management. Nurses' facilitation of patients to
      participate in pulmonary interventions. RESULTS: Patients displayed a greater
      understanding of their role in pulmonary interventions after their surgical
      admission than they did at preadmission. While 55% of patients preferred to make
      decisions about deep breathing and coughing exercises, three-quarters of patients
      (75%) reported they made decisions about deep breathing and coughing during their
      surgical admission. Nurses missed opportunities to engage patients in this aspect
      of pulmonary management. CONCLUSIONS: Patients appear willing to take
      responsibility for pulmonary management in the postoperative period. Nurses could
      enhance patient participation in pulmonary interventions by ensuring adequate
      information and education is provided. Facilitation of patients' participation in
      their recovery is a fundamental aspect of care delivery in this context.

PMID- 25939548
TI  - Heterologous expression of a fungal sterol esterase/lipase in different hosts:
      Effect on solubility, glycosylation and production.
AB  - Ophiostoma piceae secretes a versatile sterol-esterase (OPE) that shows high
      efficiency in both hydrolysis and synthesis of triglycerides and sterol esters.
      This enzyme produces aggregates in aqueous solutions, but the recombinant
      protein, expressed in Komagataella (synonym Pichia) pastoris, showed higher
      catalytic efficiency because of its higher solubility. This fact owes to a
      modification in the N-terminal sequence of the protein expressed in Pichia
      pastoris, which incorporated 4-8 additional amino acids, affecting its
      aggregation behavior. In this study we present a newly engineered P. pastoris
      strain with improved protein production. We also produced the recombinant protein
      in the yeast Saccharomyces cerevisiae and in the prokaryotic host Escherichia
      coli, corroborating that the presence of these N-terminal extra amino acids
      affected the protein's solubility. The OPE produced in the new P. pastoris strain
      presented the same physicochemical properties than the old one. An inactive form
      of the enzyme was produced by the bacterium, but the recombinant esterase from
      both yeasts was active even after its enzymatic deglycosylation, suggesting that
      the presence of N-linked carbohydrates in the mature protein is not essential for
      enzyme activity. Although the yield in S. cerevisiae was lower than that obtained
      in P. pastoris, this work demonstrates the importance of the choice of the
      heterologous host for successful production of soluble and active recombinant
      protein. In addition, S. cerevisiae constitutes a good engineering platform for
      improving the properties of this biocatalyst. 

PMID- 25939549
TI  - 29-Deoxymaklamicin, a new maklamicin analogue produced by a genetically
      engineered strain of Micromonospora sp. NBRC 110955.
AB  - Maklamicin is a spirotetronate-class antibiotic produced by Micromonospora sp.
      NBRC 110955, and a polyketide assembly line and a glycerate utilization system
      are involved in its biosynthesis. One tailoring step in the biosynthesis is
      predicted to be post-polyketide synthase (PKS) modification, which seems to be
      catalysed by putative cytochrome P450 monooxygenases, MakC2 and/or MakC3. In this
      study, we characterized makC2 and makC3 in the biosynthesis of maklamicin and
      identified a new maklamicin analogue from a makC2 disruptant. Gene deletion of
      makC2 resulted in the complete loss of maklamicin production with concomitant
      accumulation of a new compound (29-deoxymaklamicin), while gene deletion of makC3
      did not affect the maklamicin production, indicating that 29-deoxymaklamicin is
      an intermediate in the biosynthetic pathway of maklamicin and should serve as the
      substrate of MakC2. 29-Deoxymaklamicin showed strong-to-modest anti-microbial
      activity against gram-positive bacteria. The fact that Streptomyces avermitilis
      heterologously expressing makC2 successfully converted 29-deoxymaklamicin into
      maklamicin confirmed that MakC2 is the final-step hydroxylase in the formation of
      mature maklamicin.

PMID- 25939550
TI  - Acute hepatitis C virus re-infection in a heterosexual HIV-positive partner.

PMID- 25939551
TI  - Modulation of Pharmacokinetic and Cytotoxicity Profile of Imatinib Base by
      Employing Optimized Nanostructured Lipid Carriers.
AB  - PURPOSE: To prepare, optimize and characterize imatinib-loaded nanostructured
      lipid carriers (IMT-NLC), and evaluate their pharmacokinetic and cytotoxicity
      characteristics. METHODS: IMT-NLC was prepared by hot homogenization method, and
      optimized by an approach involving Plackett-Burman design (PBD) and central
      composite design (CCD). An in vivo pharmacokinetic study was conducted in rats
      after both oral and intravenous administration. The in vitro cytotoxicity was
      evaluated by MTT assay on NCI-H727 cell-lines. RESULTS: PBD screening, followed
      by optimization by CCD and desirability function, yielded an optimized condition
      of 0.054, 6% w/w, 2.5% w/w and 1.25% w/v for organic-to-aqueous phase ratio
      (O/A), drug-to-lipid ratio (D/L), amount of lecithin (Lec) and amount of Tween(r)
      20 (Tw20) respectively. The optimized IMT-NLC exhibited a particle size (Sz) of
      148.80 +/- 1.37 nm, polydispersity index (PDI) 0.191 +/- 0.017 of and zeta
      potential of -23.0 +/- 1.5 mV, with a drug loading (DL) of 5.48 +/- 0.01% and
      encapsulation efficiency (EE) of 97.93 +/- 0.03%. IMT-NLC displayed sustained IMT
      release in vitro, significantly enhanced in vivo bioavailability of IMT after
      intravenous and oral administration, and greater in vitro cytotoxicity on NCI
      H727 cells, compared with free IMT. CONCLUSION: A combined DoE approach enabled
      accurate optimization and successful preparation of IMT-NLC with enhanced in vivo
      pharmacokinetic and in vitro cytotoxicity characteristics.

PMID- 25939552
TI  - Across-Species Scaling of Monoclonal Antibody Pharmacokinetics Using a Minimal
      PBPK Model.
AB  - PURPOSE: To examine the across-species scalability of monoclonal antibody (mAb)
      pharmacokinetics (PK) and assess similarities in tissue distribution across
      species using a recently developed minimal PBPK (mPBPK) model. METHODS: Twelve
      sets of antibody PK data from various species were obtained from the literature,
      which were jointly and individually analyzed. In joint analysis, vascular
      reflection coefficients for tissues with either tight (sigma 1 ) or leaky
      endothelium (sigma 2 ) were assumed consistent across species with systemic
      clearance allometrically scaled (CL = a?BW (b) ). Four parameters (sigma 1 ,
      sigma 2 , a, and b) were estimated in the joint analysis. In addition, the PK
      from each species was individually analyzed to assess species similarities in
      tissue distribution. RESULTS: Twelve mAb PK profiles were well-captured by the
      mPBPK model in the joint analysis. The estimated sigma 1 ranged 0.690 to 0.999
      with an average of 0.908; and sigma 2 ranged 0.258 to 0.841 with an average of
      0.579. Clearance was reasonably scaled and b ranged 0.695 to 1.27 averaging 0.91.
      Predictions of plasma concentrations for erlizumab and canakinumab in humans
      using parameters obtained from fitting animal data were consistent with actual
      measurements. CONCLUSIONS: Therapeutic mAbs given IV usually exhibit
      biexponential kinetics with their distribution properties best captured using
      physiological concepts. The mPBPK modeling approach may facilitate efforts in
      translating antibody distribution and overall PK across species.

PMID- 25939553
TI  - Users of home-care services in a Nordic welfare state under marketisation: the
      rich, the poor and the sick.
AB  - Stricter access to public services, outsourcing of municipal services and
      increasing allocation of public funding for the purchase of private services have
      resulted in a marketisation wave in Finland. In this context of a Nordic welfare
      state undergoing marketisation, this paper aims to examine the use of Finnish
      care services among older people and find out who are using these new kinds of
      private services. How wide is their use and do the users of private care services
      differ from those who are using public services? How usual is it to mix both
      public and private care services? The questionnaire survey data set used here was
      gathered in 2010 among the population aged 75 and over in the cities of Jyvaskyla
      and Tampere (N = 1436). The methods of analysis used include cross-tabulation,
      chi-square tests and multinomial logistic regression. The findings showed that
      among those respondents who used care services (n = 681), 50% used only public
      services, 24% utilised solely private services and the remaining 26% used both
      kinds of services. Users of solely private services had significantly higher
      income and education as well as better health than those using public services
      only. The users of public services had the lowest education and income levels and
      usually lived in rented housing. The third group, those mixing both public and
      private services, reported poorer health than others. The results increase
      concerns about the development towards a two-tier service system, jeopardising
      universalistic Nordic principles, and also suggest that older people with the
      highest needs do not receive adequate services without complementing their public
      provisions with private services.

PMID- 25939554
TI  - Altered germinal center reaction and abnormal B cell peripheral maturation in
      PI3KR1-mutated patients presenting with HIGM-like phenotype.

PMID- 25939555
TI  - Experimental models for posterior capsule opacification research.
AB  - Millions of people worldwide are blinded due to cataract formation. At present
      the only means of treating a cataract is through surgical intervention. A modern
      cataract operation involves the creation of an opening in the anterior lens
      capsule to allow access to the fibre cells, which are then removed. This leaves
      in place a capsular bag that comprises the remaining anterior capsule and the
      entire posterior capsule. In most cases, an intraocular lens is implanted into
      the capsular bag during surgery. This procedure initially generates good visual
      restoration, but unfortunately, residual lens epithelial cells undergo a wound
      healing response invoked by surgery, which in time commonly results in a
      secondary loss of vision. This condition is known as posterior capsule
      opacification (PCO) and exhibits classical features of fibrosis, including
      hyperproliferation, migration, matrix deposition, matrix contraction and
      transdifferentiation into myofibroblasts. These changes alone can cause visual
      deterioration, but in a significant number of cases, fibre differentiation is
      also observed, which gives rise to Soemmering's ring and Elschnig's pearl
      formation. Elucidating the regulatory factors that govern these events is
      fundamental in the drive to develop future strategies to prevent or delay visual
      deterioration resulting from PCO. A range of experimental platforms are available
      for the study of PCO that range from in vivo animal models to in vitro human cell
      and tissue culture models. In the current review, we will highlight some of the
      experimental models used in PCO research and provide examples of key findings
      that have resulted from these approaches. 

PMID- 25939556
TI  - Chiropractors' characteristics associated with physician referrals: results from
      a survey of Canadian doctors of chiropractic.
AB  - OBJECTIVE: The purpose of this study was to identify characteristics of Canadian
      doctors of chiropractic (DCs) associated with the number of patients referred by
      medical doctors (MDs). METHODS: Secondary data analyses were performed on the
      2011 cross-sectional survey of the Canadian Chiropractic Resources Databank. The
      Canadian Chiropractic Resources Databank survey included 81 questions about the
      practice of DCs. Of the 6533 mailed questionnaires, 2529 (38.7%) were returned
      and 489 did not meet our inclusion criteria. Our analyzed sample included 2040
      respondents. Bivariate analyses were conducted between predetermined potential
      predictors and the annual number of patients referred by MDs, and negative
      binomial multivariate regression was performed. RESULTS: On average, DCs reported
      receiving 15.6 (standard deviation, 31.3) patient referrals from MDs per year and
      nearly one-third did not receive any. The type of clinic (multidisciplinary with
      MD), the province of practice (Atlantic provinces), the number of treatments
      provided per week, the number of practicing hours, rehabilitation and sports
      injuries as the main sector of activity, prescription of exercises, use of heat
      packs and ultrasound, and the percentage of patients referred to other health
      care providers were associated with a higher number of MD referrals to DCs. The
      percentage of patients with somatovisceral conditions, using a particular
      chiropractic technique (hole in one and Thompson), taking his/her own
      radiographs, being the client of a chiropractic management service, and
      considering maintenance/wellness care as a main sector of activity were
      associated with fewer MD referrals. CONCLUSION: Canadian DCs who interacted with
      other health care workers and who focus their practice on musculoskeletal
      conditions reported more referrals from MDs.

PMID- 25939557
TI  - A new approach to the measurement of pelvic asymmetry: proposed methods and
      reliability.
AB  - OBJECTIVE: This is a methodological study presenting a novel method of pelvic
      asymmetry (PA) measurement for use in the research laboratory setting. The
      purpose of the study is (1) to establish intrarater and interrater reliability of
      the proposed measures of PA, (2) to verify the influence of repeated measurements
      on the reliability, and (3) to assess correlation between the proposed measures
      of PA. METHODS: Twelve healthy volunteers participated, and 2 teams of raters
      were involved. Registration of anatomic landmarks' positions in the optical
      motion capture system was repeated 3 times. Two asymmetry indexes were
      calculated: for pelvic torsion and for lateral pelvic tilt. Interclass
      correlation coefficients (ICCs), standard errors of measurement, and smallest
      detectable differences were used to describe the intrarater and interrater
      reliability of the 2 indexes. RESULTS: After 2 repeated registrations of pelvic
      landmarks' positions, the reliability of our asymmetry indexes was good and
      excellent. The ICCs for intrarater reliability ranged from 0.96 to 0.97; the ICCs
      for interrater reliability ranged 0.81 to 0.90. There was moderate,
      nonsignificant correlation between asymmetry indexes for pelvis torsion and for
      lateral pelvic tilt (r = 0.45, P = .14). CONCLUSION: The 2 proposed asymmetry
      indexes showed good and excellent intrarater and interrater reliability after 2
      repeated registrations of pelvic landmarks' positions and thus may be useful in
      the research laboratory setting. However, these indexes are not strongly
      correlated, which suggests that the 2 types of PA may constitute different
      clinical entities.

PMID- 25939558
TI  - Kinematic comparison and description of the 3-dimensional shoulder kinematics of
      2 shoulder rotation tests.
AB  - OBJECTIVES: The purpose of this study was to compare shoulder external rotation
      range of motion (ROM) during the hand-behind-neck (HBN) test and a standard
      shoulder external rotation test and to describe the 3-dimensional scapular motion
      during the HBN test. METHODS: An electromagnetic tracking device was used to
      assess the dominant shoulder of 14 healthy participants while performing active
      full ROM in a standard shoulder external rotation test in an elevated position
      (EREP) and in the HBN test. The humeral and scapular 3-dimensional positions at
      the end of EREP and HBN were compared using a paired-sample t test. A correlation
      analysis was performed between humeral and scapular angles to assess the
      contribution of scapular motion to the full shoulder ROM during the HBN test.
      RESULTS: No significant differences were found between the HBN test and the EREP
      at the end-range of the glenohumeral external rotation (HBN: 15.6 degrees  +/-
      6.3 degrees  vs EREP: 23.4 degrees  +/- 4.7 degrees ; P = .08) and on scapular
      internal-external rotation (HBN test: 21.2 degrees  +/- 6.3 degrees  vs EREP:
      15.6 degrees  +/- 1.8 degrees ; P = .23). Significant differences were found in
      scapular upward rotation (HBN: 21.2 degrees  +/- 6.3 degrees  vs EREP: 15.6
      degrees  +/- 1.8 degrees ; P < .01) and scapular spinal tilt (HBN: -0.4 degrees 
      +/- 2.3 degrees  vs EREP: 8.1 degrees  +/- 2.1 degrees ; P < .01). There was a
      positive correlation between the humeral angles and scapular internal and
      posterior spinal tilt angles with the HBN test. CONCLUSIONS: The results of the
      present study showed that, in young asymptomatic participants with no known
      shoulder pathology, the end-range of shoulder rotation was similar in the HBN
      test and in a standard shoulder rotation test. During the HBN test, the scapula
      assumed a more internal and anterior spinal tilted position at the end-range of
      active shoulder external rotation. These results suggest that the HBN test may be
      used to assess the end-range of glenohumeral external rotation.

PMID- 25939560
TI  - MoCA as a Screening Tool of Neuropsychological Deficits in Alcohol-Dependent
      Patients.
AB  - BACKGROUND: Alcoholism is known to be associated with cognitive deficits mainly
      concerning visuospatial capacity, executive function, memory, and attention.
      These impairments may affect treatment efficacy which should therefore be
      adapted. We evaluated the potential utility of the Montreal Cognitive Assessment
      (MoCA) to evaluate cognitive impairment in a large series of alcoholic patients
      hospitalized for withdrawal and rehabilitation. METHODS: Consecutive recruitment
      during a time period of patients admitted to an addiction treatment unit of a
      teaching hospital. Administration of the MoCA test on admission by trained staff
      members. RESULTS: A total of 166 patients aged 49.9 +/- 9.2 years were included.
      Mean duration of administration was 20 minutes. The mean MoCA score was 23.5 +/-
      3.5 and 68.1% had an impaired value (<26). Age was negatively and education was
      positively associated with the MoCA score. Significant cognitive deficits
      concerned visuospatial capacity, attention, fluency, abstraction, and delayed
      recall. Neither age nor sex was significantly related to the MoCA score, while
      having a high education level (>12 years) significantly increased the likelihood
      of having a high MoCA score. CONCLUSIONS: Owing to their severity and frequency,
      screening for cognitive deficits is necessary in alcoholics during
      rehabilitation. MoCA is an appropriate tool for this purpose.

PMID- 25939559
TI  - Life is ... great! Emotional attention during instructed and uninstructed
      ambiguity resolution in relation to depressive symptoms.
AB  - Attention and interpretation biases are closely involved in depression. However,
      it is unclear whether they reflect processing tendencies (i.e., driven by
      schemas) and/or ability-related processes (i.e., dependent on attentional
      control). This study tested depressive symptom severity, attention bias, and
      interpretation bias associations under both processing conditions. Fifty-two
      participants completed two versions of the scrambled sentences test (to measure
      interpretation bias) while eye movements were recorded (to measure attention
      bias). Participants were instructed to unscramble sentences by reporting the
      first sentence coming to mind (tendency version) and in a fixed, positive manner
      (ability version). Depressive symptom severity was correlated with attention bias
      under both conditions. Attention bias acted as an intervening variable in the
      relation between depressive symptoms and interpretation bias during ability
      processes. These findings suggest that attention biases reflect both processing
      tendencies and ability dysfunctions, with attentional control as a relevant
      mechanism in the interpretation of emotional material. 

PMID- 25939561
TI  - Cluster of inhibitors among adult inpatients with haemophilia in a single
      institution.

PMID- 25939562
TI  - Perceived Barriers to the Use of High-Fidelity Hands-On Simulation Training for
      Contrast Reaction Management: Why Programs are Not Using It.
AB  - Although subjective and objective benefits of high-fidelity simulation have been
      reported in medicine, there has been slow adoption in radiology. The purpose of
      our study was to identify the perceived barriers in the use of high-fidelity
      hands-on simulation for contrast reaction management training. An IRB exempt 32
      questions online web survey was sent to 179 non-military radiology residency
      program directors listed in the Fellowship and Residency Electronic Interactive
      Database Access system (FREIDA). Survey questions included the type of contrast
      reaction management training, cost, time commitment of residents and faculty, and
      the reasons for not using simulation training. Responses from the survey were
      summarized as count (percentage), mean +/- standard deviation (SD), or median
      (range). 84 (47%) of 179 programs responded, of which 88% offered CRM training.
      Most (72%) conducted the CRM training annually while only 4% conducted it more
      frequently. Didactic lecture was the most frequently used training modality
      (97%), followed by HFS (30%) and computer-based simulation (CBS) (19%); 5.5% used
      both HFS and CBS. Of the 51 programs that offer CRM training but do not use HFS,
      the most common reason reported was insufficient availability (41%). Other
      reported reasons included cost (33%), no access to simulation centers (33%), lack
      of trained faculty (27%) and time constraints (27%). Although high-fidelity hands
      on simulation training is the best way to reproduce real-life contrast reaction
      scenarios, many institutions do not provide this training due to constraints such
      as cost, lack of access or insufficient availability of simulation labs, and lack
      of trained faculty. As a specialty, radiology needs to better address these
      barriers at both an institutional and national level.

PMID- 25939563
TI  - Reply: To PMID 25659356.

PMID- 25939564
TI  - Female oral and maxillofacial surgeons career choices.

PMID- 25939565
TI  - Re: Dr Laskin's Perspective.

PMID- 25939566
TI  - Re: The role of women in academic oral and maxillofacial surgery.

PMID- 25939567
TI  - Letters to the Editor Regarding Dr. Laskin's Perspectives Article.

PMID- 25939568
TI  - Translational Research-Enhancing the Health of Children and their Parents.

PMID- 25939569
TI  - Sulfur-Assisted Phenyl Migration from Phosphorus to Platinum in PtW2 and PtMo2
      Clusters Containing Thioether-Functionalized Short-Bite Ligands of the
      Bis(diphenylphosphanyl)amine-Type.
AB  - The reactivity of dichloroplatinum(II) complexes containing thioether
      functionalized bis(diphenylphosphanyl)amines of formula (Ph2P)2N(CH2)2SR (R =
      (CH2)5CH3, CH2Ph) toward group 6 carbonylmetalates Na[M(CO)3Cp] (M = Mo or W, Cp
      = cyclopentadienyl) was explored. Reactions with two or more equivalents of
      Na[M(CO)3Cp] (M = Mo or W) afforded the trinuclear complexes of general formula
      [PtPh{M(CO)3Cp}{MU-P(Ph)N(CH2CH2SR)(PPh2)-kappa(3)P,P,S}M(CO)2Cp] (3 M = Mo, R =
      (CH2)5CH3; 4 M = Mo, R = CH2Ph; 9 M = W, R = (CH2)5CH3; 10 M = W, R = CH2Ph), the
      structure of which consists of a six-membered platinacycle condensed with a four
      membered M-P-N- P cycle, together with small amounts of isomeric PtM2 clusters
      [PtM2(CO)5Cp2{(Ph2P)2N(CH2CH2SR)-kappa(2)P,P}] (5 M = Mo, R = (CH2)5CH3; 6 M =
      Mo, R = CH2Ph; 11 M = W, R = (CH2)5CH3; 12 M = W, R = CH2Ph) in which the ligand
      (Ph2P)2NR solely chelates the Pt atom or bridges an M-Pt bond as in
      [PtM2(CO)5Cp2{MU-(Ph2P)2N(CH2CH2SR)-kappa(2)P,P}] (7 M = Mo, R = (CH2)5CH3; 8 M =
      Mo, R = CH2Ph; 13 M = W, R = (CH2)5CH3; 14 M = W, R = CH2Ph). The synthesis of
      the trinuclear complexes 3, 4, 9, and 10 entails an unexpected P-phenyl bond
      cleavage reaction and phenyl migration onto Pt. When only 1 equiv of Na[M(CO)3Cp]
      (M = Mo or W) was used, the heterodinuclear products of monosubstitution
      [PtCl{M(CO)3Cp}{Ph2PN(R)PPh2-P,P}] (15 M = Mo, R = (CH2)5CH3; 16 M = Mo, R =
      CH2Ph; 17 M = W, R = (CH2)5CH3; 18 M = W, R = CH2Ph) were obtained, which are the
      precursors to the bicyclic products 3, 4, 9, and 10, respectively. Density
      functional calculations were performed to study the thermodynamics of the
      formation of all the new complexes, to evaluate the relative stabilities of the
      isomeric chelated and bridged forms, and to trace the mechanism of formation of
      the phosphanido-bridged products 3, 4, 9, and 10. It was concluded that Pt(II)
      complexes containing a thioether-functionalized short-bite ligand,
      [PtCl2{Ph2PN(R)PPh2}], react with Na[M(CO)3Cp] to yield first heterodinuclear Pt
      M and then heterotrinuclear PtM2 complexes resulting from the activation of a P-C
      bond in one of the PPh2 groups and phenyl migration to Pt. The critical role of
      an intramolecular thioether group was demonstrated. 

PMID- 25939570
TI  - Failures in communication through documents and documentation across the
      perioperative pathway.
AB  - AIMS AND OBJECTIVES: To explore how communication failures occur in documents and
      documentations across the perioperative pathway in nurses' interactions with
      other nurses, surgeons and anaesthetists. BACKGROUND: Documents and documentation
      are used to communicate vital patient and procedural information among nurses,
      and in nurses' interactions with surgeons and anaesthetists, across the
      perioperative pathway. Previous research indicates that communication failure
      regularly occurs in the perioperative setting. DESIGN: A qualitative study was
      undertaken. METHODS: The study was conducted over three hospitals in Melbourne,
      Australia. One hundred and twenty-five healthcare professionals from the
      disciplines of surgery, anaesthesia and nursing participated in the study. Data
      collection commenced in January 2010 and concluded in October 2010. Data were
      generated through 350 hours of observation, two focus groups and 20 semi
      structured interviews. A detailed thematic analysis was undertaken. RESULTS:
      Communication failure occurred owing to a reliance on documents and documentation
      to transfer information at patient transition points, poor quality documents and
      documentation, and problematic access to information. Institutional ruling
      practices of professional practice, efficiency and productivity, and fiscal
      constraint dominated the coordination of nurses', surgeons' and anaesthetists'
      communication through documents and documentation. These governing practices
      configured communication to be incongruous with reliably meeting safety and
      quality objectives. CONCLUSIONS: Communication failure occurred because important
      information was sometimes buried in documents, insufficient, inaccurate, out-of
      date or not verbally reinforced. Furthermore, busy nurses were not always able to
      access information they required in a timely manner. Patient safety was affected,
      which led to delays in treatment and at times inadequate care. RELEVANCE TO
      CLINICAL PRACTICE: Organisational support needs to be provided to nurses,
      surgeons and anaesthetists so they have sufficient time to complete, locate, and
      read documents and documentation. Infrastructure supporting communication
      technologies should be implemented to enable the rapid retrieval, entry, and
      dispersion of information.

PMID- 25939571
TI  - Circularly polarized luminescence of AIE-active chiral O-BODIPYs induced via
      intramolecular energy transfer.
AB  - Two AIE-active chiral BINOL-based O-BODIPY enantiomers (R/S-5) were synthesized
      and showed mirror-image red-color CPL induced via intramolecular energy transfer.
      The chiroptical properties of the molecules indicate that the chirality of
      electronic ground and excited states is stable and independent of aggregation.

PMID- 25939572
TI  - Fabrication of inorganic hydroxyapatite nanoparticles and organic biomolecules
      dual encapsulated alginate microspheres.
AB  - Inorganic hydroxyapatite nanoparticles (HANPs) and two kinds of organic
      biomolecules (i.e., fluorescent dye rhodamine 6G and protein lysozyme) were
      coencapsulated into alginate microspheres through an air dynamical atomization
      with optimized operation conditions. The synthesized microspheres have several
      advantages: HANP provides osteoconductivity and mechanical strength, rhodamine 6G
      (R6G) and lysozyme act as model drugs, and alginate provides excellent
      biocompatibility and carboxylate functionality. The results of fluorescent
      microscopic images indicated the successful dual encapsulation of HANPs and
      lysozyme inside the alginate microspheres. Furthermore, the results of 3- (4,5
      cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay showed that the
      fabricated alginate microspheres could be uptaken by HepG2 without apparent
      cytotoxicity. The dual encapsulated alginate microspheres fabricated in this
      study show great potential in many biomedical applications.

PMID- 25939573
TI  - Airway compromise in children with anterior neck burns: Beware the scalded child.
AB  - AIM: The aim of the study was to describe characteristics of children with
      anterior neck burns admitted to our Paediatric Intensive Care Unit (PICU) and to
      highlight potential airway complications associated with these injuries,
      especially in children with scalds. METHODS: Retrospective review of children
      with anterior neck burns requiring admission to PICU January 2004-December 2013.
      RESULTS: Fifty-two children with anterior neck burns were admitted; average age
      6.6 years. Thirty sustained flame/explosion injuries; 22 scalds. Seventy-nine per
      cent were male. Mean total body surface area (TBSA) burn 21%. Forty-seven were
      intubated. Some primary reasons for intubation included unconsciousness,
      inhalational/ingestion/direct airway injury and large TBSA. Majority, however,
      required intubation for airway complications secondary to subcutaneous/soft
      tissue anterior neck oedema not associated with airway
      injury/ingestion/inhalational burns. The scalds subgroup mean age was 2.3 years.
      Eighty-two per cent were male. Mean TBSA 18%. There were no
      inhalational/ingestion/airway injuries. Nineteen children were intubated; average
      9.3 h post-injury. Majority (63%) were intubated post-arrival in the Burn Unit,
      compared with flame/explosion group (32%). Primary reasons for intubation
      included large burns, although majority (74%) required intubation for airway
      complications secondary to subcutaneous and soft tissue anterior neck oedema. For
      the flame/explosion group this was the case in only 46%, with other primary
      reasons such as unconsciousness or inhalational injury being the immediate
      precedent. CONCLUSION: These results demonstrate that subcutaneous and soft
      tissue oedema secondary to anterior neck burns may contribute to airway narrowing
      and compromise requiring intubation. When assessing children's airways, evolving
      oedema should be recognised and higher observation or early intubation considered
      regardless of the mechanism of injury.

PMID- 25939574
TI  - Cerebrovascular endothelin-1 hyper-reactivity is associated with transient
      receptor potential canonical channels 1 and 6 activation and delayed cerebral
      hypoperfusion after forebrain ischaemia in rats.
AB  - AIM: In this study, we aimed to investigate whether changes in cerebrovascular
      voltage-dependent calcium channels and non-selective cation channels contribute
      to the enhanced endothelin-1-mediated vasoconstriction in the delayed
      hypoperfusion phase after experimental transient forebrain ischaemia. METHODS:
      Experimental forebrain ischaemia was induced in Wistar male rats by a two-vessel
      occlusion model, and the cerebral blood flow was measured by magnetic resonance
      imaging two days after reperfusion. In vitro vasoreactivity studies,
      immunofluorescence and quantitative PCR were performed on cerebral arteries from
      ischaemic or sham-operated rats to evaluate changes in vascular voltage-dependent
      calcium channels, transient receptor potential canonical channels as well as
      endothelin-1 receptor function and expression. RESULTS: The expression of
      transient receptor potential canonical channels 1 and 6 in the vascular smooth
      muscle cells was enhanced and correlated with decreased cerebral blood flow two
      days after forebrain ischaemia. Furthermore, under conditions when voltage
      dependent calcium channels were inhibited, endothelin-1-induced cerebrovascular
      contraction was enhanced and this enhancement was presumably mediated by Ca(2+)
      influx via upregulated transient receptor potential canonical channels 1 and 6.
      CONCLUSIONS: Our data demonstrates that endothelin-1-mediated influx of
      extracellular Ca(2+) activates transient receptor potential canonical channels 1
      and 6 in cerebral vascular smooth muscle cells. This seems to have an important
      role in the enhanced cerebral vasoconstriction in the delayed post-ischaemic
      hypoperfusion phase after experimental forebrain ischaemia.

PMID- 25939575
TI  - Is immunoglobulin E to Staphylococcus aureus enterotoxins associated with asthma
      at 20 years?
AB  - BACKGROUND: In adults, subjects sensitized to Staphylococcus aureus enterotoxins
      (SE) seem to have an increased risk of asthma, whereas this association is less
      clear in childhood and adolescence. The primary aim of the present analysis was
      to examine the association between sensitization to SE and asthma at the age of
      20 years. METHODS: The German Multicentre Allergy Study recruited 1314 healthy
      newborns in 1990. We analyzed data from 61 asthmatics (based on at least two
      criteria: physician diagnosed asthma ever, wheezing in the last 12 months, asthma
      medication in the last 12 months) and 122 healthy study participants at age 20.
      In serum, specific Immunoglobulin E (IgE) to SE and common aeroallergens were
      measured. The association between asthma at age 20 and sensitization to SE was
      estimated by logistic regression models considering allergic, socio-demographic,
      and lifestyle factors as potential confounders. RESULTS: Fifty-five percent of
      the included participants were female. At age 20, subjects sensitized to SE were
      more likely to have asthma than not-sensitized subjects: raw odds ratio (OR) 2.5,
      95%-confidence interval (95%CI) [1.3-4.7]; adjusted OR 1.6, 95%CI [0.8-3.4].
      CONCLUSION: Asthmatics at age 20 were more often sensitized to SE compared to
      controls. Our study may indicate a moderate relationship between SE-sensitization
      and asthma; however, this association attenuated after adjusting for potential
      confounders and was no longer statistically significant. Longitudinal
      investigations with SE-IgE measurements at different time points in larger
      samples are needed to explore the temporal manner of this relationship.

PMID- 25939576
TI  - Illustrating ontogenetic change in the dentition of the Nile monitor lizard,
      Varanus niloticus: a case study in the application of geometric morphometric
      methods for the quantification of shape-size heterodonty.
AB  - Many recent attempts have been made to quantify heterodonty in non-mammalian
      vertebrates, but the majority of these are limited to Euclidian measurements. One
      taxon frequently investigated is Varanus niloticus, the Nile monitor. Juveniles
      possess elongate, pointed teeth (caniniform) along the entirety of the dental
      arcade, whereas adults develop large, bulbous distal teeth (molariform). The
      purpose of this study was to present a geometric morphometric method to quantify
      V. niloticus heterodonty through ontogeny that may be applied to other non
      mammalian taxa. Data were collected from the entire tooth row of 19 dry skull
      specimens. A semilandmark analysis was conducted on the outline of the
      photographed teeth, and size and shape were derived. Width was also measured with
      calipers. From these measures, sample ranges and allometric functions were
      created using multivariate statistical analyses for each tooth position
      separately, as well as overall measures of heterodonty for each specimen based on
      morphological disparity. The results confirm and expand upon previous studies,
      showing measurable shape-size heterodonty in the species with significant
      differences at each tooth position. Tooth size increases with body size at most
      positions, and the allometric coefficient increases at more distal positions.
      Width shows a dramatic increase at the distal positions with ontogeny, often
      displaying pronounced positive allometry. Dental shape varied in two noticeable
      ways, with the first composing the vast majority of shape variance: (i)
      caniniformy vs. molariformy and (ii) mesially leaning, 'rounded' apices vs.
      distally leaning, 'pointed' apices. The latter was twice as influential in the
      mandible, a consequence of host bone shape. Mesial teeth show no significant
      shape change with growth, whereas distal teeth change significantly due primarily
      to an increase in molariformy. Overall, heterodonty increases with body size
      concerning both tooth size and shape, but shape heterodonty changes in the
      mandible are much less pronounced. Although it is unclear to what degree V.
      niloticus specializes in hard prey items (durophagy), previous studies of varanid
      feeding behavior, along with research on analogous durophagous vertebrates,
      indicate a division of labor along the tooth row in adults, due to a possible
      transition to at least a partial durophagous niche. The geometric morphometric
      method proposed here, although not without its own limitations, may be ideal for
      use with a number of dental morphotypes in the future. 

PMID- 25939578
TI  - Guidelines for the management of acute gastroenteritis in children in Europe.

PMID- 25939579
TI  - New strategies in organ preservation: current and future role of machine
      perfusion in organ transplantation.

PMID- 25939577
TI  - Brain Pathology in Adult Rats Treated With Domoic Acid.
AB  - Domoic acid (DA) is a neurotoxin reported to produce damage to the hippocampus,
      which plays an important role in memory. The authors inoculated rats
      intraperitoneally with an effective toxic dose of DA to study the distribution of
      the toxin in major internal organs by using immunohistochemistry, as well as to
      evaluate the induced pathology by means of histopathologic and
      immunohistochemical methods at different time points after toxin administration
      (6, 10, and 24 hours; 5 and 54 days). DA was detected by immunohistochemistry
      exclusively in pyramidal neurons of the hippocampus at 6 and 10 hours after
      dosing. Lesions induced by DA were prominent at 5 days following treatment in
      selected regions of the brain: hippocampus, amygdala, piriform and perirhinal
      cortices, olfactory tubercle, septal nuclei, and thalamus. The authors found 2
      types of lesions: delayed death of selective neurons and large areas of necrosis,
      both accompanied by astrocytosis and microgliosis. At 54 days after DA exposure,
      the pathology was characterized by still-distinguishable dying neurons, calcified
      lesions in the thalamus, persistent astrocytosis, and pronounced microgliosis.
      The expression of nitric oxide synthases suggests a role for nitric oxide in the
      pathogenesis of neuronal degeneration and chronic inflammation induced by DA in
      the brain. 

PMID- 25939580
TI  - Use of acid-suppressive therapy before anti-reflux surgery in 2922 patients: a
      nationwide register-based study in Denmark.
AB  - BACKGROUND: Guidelines recommend that patients with gastro-oesophageal reflux
      disease are adequately treated with acid-suppressive therapy before undergoing
      anti-reflux surgery. Little is known of the use of acid-suppressive drugs before
      anti-reflux surgery. AIM: To determine the use of proton pump inhibitors and H2 
      receptor antagonists in the year before anti-reflux surgery. METHODS: A
      nationwide retrospective study of all patients aged >=18 undergoing first-time
      anti-reflux surgery in Denmark during 2000-2012 using data from three different
      sources: the Danish National Register of Patients, the Danish National
      Prescription Register, and the Danish Person Register. RESULTS: The study
      population thus included 2922 patients (median age: 48 years, 55.7% male). The
      annual proportion of patients redeeming >=180 DDD of acid-suppressive therapy
      increased from 17.0% 5 years before anti-reflux surgery to 64.9% 1 year before.
      The probability for inadequate dosing 1 year before surgery (<180 DDD) was
      significantly increased for younger patients, patients operated in the period
      2000-2003, patients who had not undergone pre-surgical manometry, pH- or
      impedance monitoring, and patients who had not redeemed prescriptions on NSAID or
      anti-platelet drugs. CONCLUSION: Compliance with medical therapy should be
      evaluated thoroughly before planning anti-reflux surgery, as a high proportion of
      patients receive inadequate dosing of acid-suppressive therapy prior to the
      operation.

PMID- 25939582
TI  - Managing Anxiety in Children With ADHD Using Cognitive-Behavioral Therapy: A
      Pilot Randomized Controlled Trial.
AB  - OBJECTIVE: This pilot randomized controlled trial examined the acceptability and
      feasibility of a cognitive-behavioral therapy (CBT) intervention for children
      with ADHD and anxiety, and provided preliminary information on child and family
      outcomes. METHOD: Children with ADHD and anxiety (8-12 years) were randomized to
      receive an adapted version of the Cool Kids CBT program or usual clinical care.
      Key outcomes included feasibility and acceptability of the intervention
      (participant enrollment, drop-out, intervention session attendance), remission of
      anxiety assessed via diagnostic interview, ADHD symptom severity, quality of life
      (QoL), and parent mental health. RESULTS: Twelve children participated (67%
      uptake). Most families attended all 10 intervention sessions, with no drop-outs.
      Intervention participants had marked improvements in both child and family well
      being by parent and teacher report, including anxiety, ADHD symptom severity,
      QoL, and parent mental health. CONCLUSION: Non-pharmacological interventions may
      improve important domains of functioning for children with ADHD and anxiety,
      including ADHD symptom severity.

PMID- 25939583
TI  - Longitudinal Smoking Patterns: Do They Predict Symptoms of ADHD in Adults?
AB  - OBJECTIVE: The objective of this study was to assess whether comparisons of
      longitudinal smoking trajectories predict differences in symptoms of ADHD in
      adults. METHOD: Participants were interviewed 7 times between 14 and 43 years of
      age. ADHD symptoms at outcome were assessed with the World Health Organization
      ADHD Self-Report Scale. Bivariate and multivariate linear regression analyses
      assessed the associations between the trajectories of smoking and ADHD symptoms.
      RESULTS: The multivariate analysis (R 2 = .12) indicated that compared with being
      nonsmokers, the probability of being in the heavy/continuous group (standardized
      regression coefficient [SRC] = .17, p < .01) and in the late starter group (SRC =
      .11, p < .05) were significantly associated with adult ADHD symptoms. CONCLUSION:
      Longitudinal smoking patterns were associated with ADHD symptoms in adults.
      Chronic smoking jeopardizes both physical health and the ability to fulfill adult
      roles as employees, family members, and friends. Smoking cessation in adolescence
      may lessen the likelihood of ADHD symptoms in adulthood.

PMID- 25939585
TI  - Theoretical simulation of the reduction of graphene oxide by lithium
      naphthalenide.
AB  - Based on density functional theory, we investigated the mechanism of graphene
      oxide reduction by lithium naphthalenide (C10H8Li). C10H8(-) easily reacts with
      GO to form a neutral C10H8 and the negatively charged GO, which can attach to
      Li(+) ions to form lithium oxide on a graphene skeleton. The reduction mechanism
      is similar to the reduction of GO by metallic Li; the C10H8 is used to disperse
      Li in THF solution. Furthermore, the lithium oxide on GO can react with CO2 to
      form Li2CO3 and be further reduced by MeOH washing. In the negatively charged GO,
      the carboxyl at the edge of GO transfers an electron to GO and releases a CO2
      molecule by overcoming a barrier of 0.19 eV. CO2 can also be adsorbed by lithium
      oxide to form Li2CO3 that is tightly attached on graphene skeleton. After GO is
      partially reduced, the adsorption of CO2 eliminates O in the form of Li2CO3
      without any barrier. This mechanism can be helpful for further understanding the
      nature of GO reduction among various reducing agents and for exploring new and
      efficient GO reducing agents. 

PMID- 25939581
TI  - Amyloid beta: one of three danger-associated molecules that are secondary
      inducers of the proinflammatory cytokines that mediate Alzheimer's disease.
AB  - This review concerns how the primary inflammation preceding the generation of
      certain key damage-associated molecular patterns (DAMPs) arises in Alzheimer's
      disease (AD). In doing so, it places soluble amyloid beta (Abeta), a protein
      hitherto considered as a primary initiator of AD, in a novel perspective. We note
      here that increased soluble Abeta is one of the proinflammatory cytokine-induced
      DAMPs recognized by at least one of the toll-like receptors on and in various
      cell types. Moreover, Abeta is best regarded as belonging to a class of DAMPs, as
      do the S100 proteins and HMBG1, that further exacerbate production of these same
      proinflammatory cytokines, which are already enhanced, and induces them further.
      Moreover, variation in levels of other DAMPs of this same class in AD may explain
      why normal elderly patients can exhibit high Abeta plaque levels, and why
      removing Abeta or its plaque does not retard disease progression. It may also
      explain why mouse transgenic models, having been designed to generate high Abeta,
      can be treated successfully by this approach. 

PMID- 25939584
TI  - Evaluating an extended rehabilitation service for stroke patients (EXTRAS): study
      protocol for a randomised controlled trial.
AB  - BACKGROUND: Development of longer term stroke rehabilitation services is limited
      by lack of evidence of effectiveness for specific interventions and service
      models. We describe the protocol for a multicentre randomised controlled trial
      which is evaluating an extended stroke rehabilitation service. The extended
      service commences when routine 'organised stroke care' (stroke unit and early
      supported discharge (ESD)) ends. METHODS/DESIGN: This study is a multicentre
      randomised controlled trial with health economic and process evaluations. It is
      set within NHS stroke services which provide ESD. Participants are adults who
      have experienced a new stroke (and carer if appropriate), discharged from
      hospital under the care of an ESD team. The intervention group receives an
      extended stroke rehabilitation service provided for 18 months following
      completion of ESD. The extended rehabilitation service involves regular contact
      with a senior ESD team member who leads and coordinates further rehabilitation.
      Contact is usually by telephone. The control group receives usual stroke care
      post-ESD. Usual care may involve referral of patients to a range of
      rehabilitation services upon completion of ESD in accordance with local clinical
      practice. Randomisation is via a central independent web-based service. The
      primary outcome is extended activities of daily living (Nottingham Extended
      Activities of Daily Living Scale) at 24 months post-randomisation. Secondary
      outcomes (at 12 and 24 months post-randomisation) are health status, quality of
      life, mood and experience of services for patients, and quality of life,
      experience of services and carer stress for carers. Resource use and adverse
      events are also collected. Outcomes are undertaken by a blinded assessor.
      Implementation and delivery of the extended stroke rehabilitation service will
      also be described. Semi-structured interviews will be conducted with a subsample
      of participants and staff to gain insight into perceptions and experiences of
      rehabilitation services delivered or received. Allowing for 25% attrition, 510
      participants are needed to provide 90% power to detect a difference in mean
      Nottingham Extended Activities of Daily Living Scale score of 6 with a 5%
      significance level. DISCUSSION: The provision of longer term support for stroke
      survivors is currently limited. The results from this trial will inform future
      stroke service planning and configuration. TRIAL REGISTRATION: This trial was
      registered with ISRCTN (identifier: ISRCTN45203373 ) on 9 August 2012.

PMID- 25939586
TI  - Psychological wellbeing in 20-year-old adults receiving repeated lifestyle
      counselling since infancy.
AB  - AIM: This study examined whether there was an association between a repeated
      dietary and lifestyle intervention that began in infancy and participants'
      psychological wellbeing at the age of 20. METHODS: We examined the psychological
      wellbeing of 457 young adults participating in the Special Turku Coronary Risk
      Factor Intervention Project (STRIP), a randomised controlled trial conducted in
      Finland between 1989 and 2011. We assessed potential differences in psychological
      wellbeing between the intervention and control groups by examining participants'
      satisfaction with life, how they rated their health, their experiences of stress
      and the consequences of experiencing stress and symptoms of depression at the age
      of 20. We also assessed socio-economic status during childhood as a potential
      confounding factor. RESULTS: We found no association between the long-term
      dietary and lifestyle intervention and participants' psychological wellbeing in
      adulthood. Adjusting for sex and childhood socio-economic status did not affect
      the results and socio-economic status did not moderate the association between
      the intervention and psychological wellbeing. CONCLUSION: Our findings showed no
      association between intensive dietary and lifestyle counselling that was
      initiated in infancy with psychological wellbeing in adulthood and the initiative
      did not appear to pose any psychological risks.

PMID- 25939587
TI  - 3D plasmonic nanobowl platform for the study of exosomes in solution.
AB  - Thin silver film coated nanobowl Surface Enhanced Raman Spectroscopy (SERS)
      substrates are used to capture exosomes in solution for SERS measurements that
      can provide biochemical analysis of intact and ruptured exosomes. Exosomes
      derived via Total Exosome Isolation Reagent (TEIR) as well as ultracentrifugation
      (UC) from the SKOV3 cell line were analyzed. Spectra of exosomes derived via TEIR
      are dominated by a signal characteristic for the TEIR kit that needs to be
      subtracted for all measurements. Differences in SERS spectra recorded at
      different times during the drying of the exosome solution are statistically
      analyzed with Principal Component Analysis (PCA). At the beginning of the drying
      process, SERS spectra of exosomes exhibit peaks characteristic for both lipids
      and proteins. Later on during the drying process, new SERS peaks develop,
      suggesting that the initially intact exosome ruptures over time. This time
      dependent evolution of SERS peaks enables analysis of exosomal membrane contents
      and the contents inside the exosomes. 

PMID- 25939588
TI  - A bioresponsive controlled-release bioassay based on aptamer-gated Au nanocages
      and its application in living cells.
AB  - A novel controlled-release bioassay for highly sensitive and selective detection
      of intracellular ATP was developed based on positive charge-modified Au nanocages
      capped with an aptamer molecular gate, and it was used successfully for
      fluorescence microscopy imaging of ATP in living cells. 

PMID- 25939589
TI  - Mango: pulp fiction?

PMID- 25939590
TI  - Newer multiple sclerosis drugs and disability scores-are key data analyses
      missing?

PMID- 25939591
TI  - Resveratrol reduces the levels of circulating androgen precursors but has no
      effect on, testosterone, dihydrotestosterone, PSA levels or prostate volume. A 4
      month randomised trial in middle-aged men.
AB  - BACKGROUND: Resveratrol is a naturally occurring polyphenol with purported
      inhibitory effects on prostate growth and cancer development. A number of studies
      have demonstrated that resveratrol reduces prostate growth in animal models and
      reduces prostate cell growth in vitro. Based on these pre-clinical findings,
      interest in resveratrol is increasing in relation to the management of benign
      prostate hyperplasia (BPH) and prostate cancer. So far, no human trials have
      evaluated the effects of resveratrol on circulating androgens, prostate size, or
      biochemical markers of prostate size. METHODS: In a randomized placebo controlled
      clinical study using two doses of resveratrol (150 mg or 1,000 mg resveratrol
      daily) for 4 months, we evaluated the effects on prostate size, prostate specific
      antigen (PSA) and sex steroid hormones in 66 middle-aged men suffering from the
      metabolic syndrome(MetS). RESULTS: At baseline, prostate size and PSA were
      positively correlated (R = 0.34, P < 0.007) as was prostate size and age (R =
      0.37, P < 0.003). Prostate size did not correlate with testosterone, free
      testosterone, dihydrotestosterone (DHT), or any other androgen precursor at
      baseline. The highest dose of resveratrol lowered the serum level of
      androstenedione 24% (P = 0.052), dehydroepiandrosterone (DHEA) 41% (P < 0.01),
      and dehydroepiandrosterone-sulphate (DHEAS) 50% (p<0.001), compared to the
      control group. However, prostate size and levels of PSA, testosterone, free
      testosterone and DHT remained unchanged. CONCLUSION: In this population of middle
      aged men suffering from MetS, high dose resveratrol (1,000 mg daily)
      administration for 4 months significantly lowered serum levels of the androgen
      precursors androstenedione, DHEA and DHEAS, whereas prostate size and circulating
      levels of PSA, testosterone, free testosterone, and dihydrotestosterone were
      unaffected. The present study suggests that resveratrol does not affect prostate
      volume in healthy middle-aged men as measured by PSA levels and CT acquired
      prostate volumes. Consequently, we find no support for the use of resveratrol in
      the treatment of benign prostate hyperplasia.

PMID- 25939592
TI  - Compression-induced HIF-1 enhances thrombosis and PAI-1 expression in mouse skin.
AB  - Pressure ulcers result from tissue hypoxia caused by external forces. Thrombosis
      due to external forces is considered important, and hypoxia inducible factor-1
      (HIF-1) is a master regulator of pressure ulcer development. To date, however,
      their causal relationship has not been determined. This study therefore
      investigated the mutual relationship between thrombosis and HIF-1 activation in
      compressed mouse skin, based on a hypothesis that HIF-1 regulation by plasminogen
      activator inhibitor-1 (PAI-1) enhances thrombosis. Compression of mouse skin
      significantly increased the numbers of thrombi and HIF-1alpha-positive cells
      compared with control skin. A thrombosis inhibitor significantly reduced the
      numbers of HIF-1alpha-positive cells and an HIF-1 inhibitor significantly
      inhibited thrombosis in compressed skin tissue, suggesting a mutual relationship
      between thrombosis and HIF-1 activation. Compression of mouse skin also enhanced
      the level of Pai-1 messenger RNA expression, but this increase was significantly
      reduced by treatment with an HIF-1 inhibitor, whereas a thrombosis inhibitor had
      no effect. These results suggested the involvement of PAI-1 in HIF-1-enhanced
      thrombosis and that an additional factor participates in regulating Pai-1
      expression in compressed skin. These findings may suggest new strategies in
      pressure ulcer management. 

PMID- 25939593
TI  - Strengthening adherence to Anti Retroviral Therapy (ART) monitoring and support:
      operation research to identify barriers and facilitators in Nepal.
AB  - BACKGROUND: Anti Retroviral Therapy (ART) is the cornerstone for comprehensive
      health sector response to Human Immunodeficiency Virus (HIV) treatment, care and
      support. Adherence of at least 95% is needed to keep HIV under control, as per
      World Health Organization (WHO) guidelines. This study was aimed at identifying
      the overall adherence level of, and barriers and facilitators to adherence for
      patients taking ART in different clinics in all five development regions of
      Nepal. METHODS: A descriptive cross-sectional study was conducted among ART
      clients receiving free ART from Government of Nepal ART clinics. A total of 435
      clients taking ART from twelve ART clinics in different regions of Nepal, aged
      fifteen years and above were interviewed on one-and-one basis using
      questionnaires developed in reference to Adult AIDS Clinical Trial Group (AACTG)
      toolkit among them data from 404 were analyzed after cleaning. Data was entered
      and analyzed using Statistical Package for Social Sciences (SPSS) software where
      the P value of < 0.05 was accepted as being statistically significant. RESULTS:
      The overall adherence in the last month (missed less than three pills total) was
      94.8% (383 out of 404). The main barrier to ART adherence was the fear of side
      effects (among 61.9% of the non adherent population) which included dizziness
      (18.1%) and headaches (15.4%). The standard wristwatch (39%) was found to be the
      most useful aid in enabling timely consumption of medication. Educational status
      (P = 0.018), drug using habits (P = 0.039) and the conducive environment at ART
      clinics (P = 0.004) were significantly associated with ART adherence. CONCLUSION:
      Improving better adherence may require a more holistic approach to treatment
      regimen and adapting it to patient daily routines. This study identifies issues
      such as pill count for assessing adherence, better access to health care
      facilities by clients, better access to medication, as well as improved
      nutritional support issues for better adherence by the population in the future.

PMID- 25939594
TI  - A rapid microwave-assisted synthesis of a sodium-cadmium metal-organic framework
      having improved performance as a CO2 adsorbent for CCS.
AB  - We report on a facile and rapid microwave-assisted method for preparing a sodium
      cadmium metal-organic framework (having coordinatively unsaturated sodium ions)
      that considerably shortens the conventional synthesis time from 5 days to 1 hour.
      The obtained (Na,Cd)-MOF showed an excellent volumetric CO2 adsorption capacity
      (5.2 mmol cm(-3) at 298 K and 1 bar) and better CO2 adsorption properties than
      those shown by the same metal-organic framework when synthesized following a more
      conventional procedure. Moreover, the newly prepared material was found to
      display high selectivity for adsorption of carbon dioxide over nitrogen, and good
      regenerability and stability during repeated CO2 adsorption-desorption cycles,
      which are the required properties for any adsorbent intended for carbon dioxide
      capture and sequestration (CSS) from the post-combustion flue gas of fossil
      fuelled power stations. 

PMID- 25939595
TI  - Correction: Bijels stabilized using rod-like particles.
AB  - Correction for 'Bijels stabilized using rod-like particles' by Niek Hijnen et
      al., Soft Matter, 2015, DOI: . 

PMID- 25939596
TI  - Somatic and gastrointestinal in vivo biotransformation rates of hydrophobic
      chemicals in fish.
AB  - To improve current bioaccumulation assessment methods, a methodology is
      developed, applied, and investigated for measuring in vivo biotransformation
      rates of hydrophobic organic substances in the body (soma) and gastrointestinal
      tract of the fish. The method resembles the Organisation for Economic Co
      operation and Development (OECD) 305 dietary bioaccumulation test but includes
      reference chemicals to determine both somatic and gastrointestinal
      biotransformation rates of test chemicals. Somatic biotransformation rate
      constants for the test chemicals ranged between 0 d(-1) and 0.38 (standard error
      [SE] 0.03)/d(-1) . Gastrointestinal biotransformation rate constants varied from
      0 d(-1) to 46 (SE 7) d(-1) . Gastrointestinal biotransformation contributed more
      to the overall biotransformation in fish than somatic biotransformation for all
      test substances but 1. Results suggest that biomagnification tests can reveal the
      full extent of biotransformation in fish. The common presumption that the liver
      is the main site of biotransformation may not apply to many substances exposed
      through the diet. The results suggest that the application of quantitative
      structure-activity relationships (QSARs) for somatic biotransformation rates and
      hepatic in vitro models to assess the effect of biotransformation on
      bioaccumulation can underestimate biotransformation rates and overestimate the
      biomagnification potential of chemicals that are biotransformed in the
      gastrointestinal tract. With some modifications, the OECD 305 test can generate
      somatic and gastrointestinal biotransformation data to develop biotransformation
      QSARs and test in vitro-in vivo biotransformation extrapolation methods.

PMID- 25939598
TI  - The role of substrate topography on the cellular uptake of nanoparticles.
AB  - Improving targeting efficacy has been a central focus of the studies on
      nanoparticle (NP)-based drug delivery nanocarriers over the past decades. As
      cells actively sense and respond to the local physical environments, not only the
      NP design (e.g., size, shape, ligand density, etc.) but also the cell mechanics
      (e.g., stiffness, spreading, expressed receptors, etc.) affect the cellular
      uptake efficiency. While much work has been done to elucidate the roles of NP
      design for cells seeded on a flat tissue culture surface, how the local physical
      environments of cells mediate uptake of NPs remains unexplored, despite the
      widely known effect of local physical environments on cellular responses in vitro
      and disease states in vivo. Here, we report the active responses of human
      osteosarcoma cells to fibrous substrate topographies and the subsequent changes
      in the cellular uptake of NPs. Our experiments demonstrate that surface
      topography modulates cellular uptake efficacy by mediating cell spreading and
      membrane mechanics. The findings provide a concrete example of the regulative
      role of the physical environments of cells on cellular uptake of NPs, therefore
      advancing the rational design of NPs for enhanced drug delivery in targeted
      cancer therapy.

PMID- 25939599
TI  - Associations between respiratory sinus arrhythmia (RSA) reactivity and effortful
      control in preschool-age children.
AB  - We tested whether respiratory sinus arrhythmia (RSA) reactivity in response to
      each of three self-regulation tasks (bird and dragon; knock-tap; and gift wrap)
      would predict self-regulation performance in a sample of 101 preschool-age
      children (M age = 4.49, SD = .64). While controlling for baseline RSA, decreases
      in RSA from bird and dragon to knock-tap (but not from baseline to bird and
      dragon) predicted a latent variable measuring self-regulation. Furthermore,
      increases in RSA from the knock-tap to gift wrap-the only task involving delay of
      gratification-were related to concurrent task performance while controlling for
      the relation between RSA reactivity and the latent self-regulation variable.
      Results suggest that the relations between RSA reactivity and self-regulatory
      ability are influenced by task-specific demands and possibly by task order.
      Furthermore, RSA reactivity appears to relate differently to performance on
      motivationally salient self-regulation tasks such as delay of gratification
      relative to cool executive function tasks.

PMID- 25939601
TI  - [In Process Citation].

PMID- 25939597
TI  - Two susceptibility loci identified for prostate cancer aggressiveness.
AB  - Most men diagnosed with prostate cancer will experience indolent disease; hence,
      discovering genetic variants that distinguish aggressive from nonaggressive
      prostate cancer is of critical clinical importance for disease prevention and
      treatment. In a multistage, case-only genome-wide association study of 12,518
      prostate cancer cases, we identify two loci associated with Gleason score, a
      pathological measure of disease aggressiveness: rs35148638 at 5q14.3 (RASA1,
      P=6.49 * 10(-9)) and rs78943174 at 3q26.31 (NAALADL2, P=4.18 * 10(-8)). In a
      stratified case-control analysis, the SNP at 5q14.3 appears specific for
      aggressive prostate cancer (P=8.85 * 10(-5)) with no association for
      nonaggressive prostate cancer compared with controls (P=0.57). The proximity of
      these loci to genes involved in vascular disease suggests potential biological
      mechanisms worthy of further investigation. 

PMID- 25939602
TI  - Early Prediction of Disease Progression in Small Cell Lung Cancer: Toward Model
      Based Personalized Medicine in Oncology.
AB  - Predictive biomarkers can play a key role in individualized disease monitoring.
      Unfortunately, the use of biomarkers in clinical settings has thus far been
      limited. We have previously shown that mechanism-based
      pharmacokinetic/pharmacodynamic modeling enables integration of nonvalidated
      biomarker data to provide predictive model-based biomarkers for response
      classification. The biomarker model we developed incorporates an underlying
      latent variable (disease) representing (unobserved) tumor size dynamics, which is
      assumed to drive biomarker production and to be influenced by exposure to
      treatment. Here, we show that by integrating CT scan data, the population model
      can be expanded to include patient outcome. Moreover, we show that in conjunction
      with routine medical monitoring data, the population model can support accurate
      individual predictions of outcome. Our combined model predicts that a change in
      disease of 29.2% (relative standard error 20%) between two consecutive CT scans
      (i.e., 6-8 weeks) gives a probability of disease progression of 50%. We apply
      this framework to an external dataset containing biomarker data from 22 small
      cell lung cancer patients (four patients progressing during follow-up). Using
      only data up until the end of treatment (a total of 137 lactate dehydrogenase and
      77 neuron-specific enolase observations), the statistical framework prospectively
      identified 75% of the individuals as having a predictable outcome in follow-up
      visits. This included two of the four patients who eventually progressed. In all
      identified individuals, the model-predicted outcomes matched the observed
      outcomes. This framework allows at risk patients to be identified early and
      therapeutic intervention/monitoring to be adjusted individually, which may
      improve overall patient survival.

PMID- 25939600
TI  - [Coagulation management in patients with liver disease].
AB  - BACKGROUND: End-stage liver disease is associated with complex alterations in
      hemostasis. Whereas prognosis is essentially affected by life-threatening
      bleeding complications in some patients, others, especially those with
      cholestatic liver diseases, suffer from thromboembolic complications. Standard
      laboratory values (SLVS; prothrombin time, activated partial thrombin time,
      platelet count) cannot sufficiently reflect the altered balance of pro- and
      anticoagulatory factors. Moreover, a couple of studies indicated that SLVS are
      not able to predict bleeding complications in patients with acute liver failure
      or decompensated liver cirrhosis. DIAGNOSIS AND THERAPY: Use of bed-side
      coagulation diagnostics such as thrombelastometry/-graphy, detection of
      thrombocyte function by multiple electrode aggregometry and selective measurement
      of single factors allows a targeted and causal therapy of hepatic coagulopathies
      especially in the context of bleeding complications or surgical interventions. In
      recent years, coagulation management guided by these new devices has contributed
      to a reduction in transfusion of allogenic blood products, which may be
      associated with undesirable side effects. DISCUSSION: The current review
      summarizes the complex pathophysiological alterations of hemostasis associated
      with advanced liver insufficiency and discusses recent upcoming diagnostics and
      coagulation management in this patient cohort.

PMID- 25939603
TI  - Repair versus Checkpoint Functions of BRCA1 Are Differentially Regulated by Site
      of Chromatin Binding.
AB  - The product of the Brca1 tumor-suppressor gene is involved in multiple aspects of
      the cellular DNA damage response (DDR), including activation of cell-cycle
      arrests and DNA double-stranded break (DSB) repair by homologous recombination.
      Prior reports demonstrated that BRCA1 recruitment to areas of DNA breakage
      depended on RAP80 and the RNF8/RNF168 E3 ubiquitin ligases. Here, we extend these
      findings by showing that RAP80 is only required for the binding of BRCA1 to
      regions flanking the DSB, whereas BRCA1 binding directly to DNA breaks requires
      Nijmegen breakage syndrome 1 (NBS1). These differential recruitment mechanisms
      differentially affect BRCA1 functions: (i) RAP80-dependent recruitment of BRCA1
      to chromatin flanking DNA breaks is required for BRCA1 phosphorylation at serine
      1387 and 1423 by ATM and, consequently, for the activation of S and G(2)
      checkpoints; and (ii) BRCA1 interaction with NBS1 upon DSB induction results in
      an NBS1-dependent recruitment of BRCA1 directly to the DNA break and is required
      for nonhomologous end-joining repair. Together, these findings illustrate that
      spatially distinct fractions of BRCA1 exist at the DSB site, which are recruited
      by different mechanisms and execute different functions in the DDR.

PMID- 25939604
TI  - Circulating Lipocalin 2 Levels Predict Fracture-Related Hospitalizations in
      Elderly Women: A Prospective Cohort Study.
AB  - Lipocalin 2 (LCN2) or neutrophil gelatinase-associated lipocalin (NGAL) is
      expressed in a wide range of cells and pathological states. Mounting evidence
      suggests lipocalin 2 may be an important regulator of bone homeostasis. Recently
      it has been suggested LCN2 is a novel mechanoresponsive gene central to the
      pathological response to low mechanical force. We undertook a prospective study
      of 1009 elderly women over 70 years of age to study the association between
      circulating LCN2 and potential associated variables, including estimated
      glomerular filtration rate, physical activity, and baseline measures of hip bone
      density and heel bone quality. Osteoporotic fractures requiring hospitalizations
      were identified from the Western Australian Data Linkage System. Over 14.5 years,
      272 (27%) of women sustained an osteoporotic fracture-related hospitalization; of
      these, 101 were hip fractures. Circulating LCN2 levels were correlated with body
      mass index and estimated glomerular filtration rate (r = 0.249, p < 0.001 and r =
      -0.481, p < 0.001, respectively) that modified the association with hip and heel
      bone measures. Per standard deviation increase in LCN2, there was a 30%
      multivariable-adjusted increase in the risk of any osteoporotic fracture (hazard
      ratio [HR] = 1.30, 95% confidence interval [CI] 1.13-1.50, p < 0.001). In
      participants with elevated LCN2 levels above the median (76.6 ng/mL), there was
      an 80% to 81% increase in the risk of any osteoporotic or hip fracture (HR =
      1.81, 95% CI 1.38-2.36, p < 0.001 and HR = 1.80, 95% CI 1.16-2.78, p = 0.008,
      respectively). These associations remained significant after adjustment for total
      hip bone mineral density (p < 0.05). In conclusion, we have demonstrated that
      circulating LCN2 levels predict future risk of osteoporotic fractures requiring
      hospitalization. Measurement of LCN2 levels may improve fracture prediction in
      addition to current fracture risk factors in the elderly, particularly in those
      with impaired renal function.

PMID- 25939605
TI  - Influence of ACTN3 R577X polymorphism on ventilatory thresholds related to
      endurance performance.
AB  - The purpose of this study was to verify the association between ACTN3
      polymorphism and physiological parameters related to endurance performance. A
      total of 150 healthy male volunteers performed a maximal incremental running test
      to determine the speeds corresponding to ventilatory threshold (VT) and
      respiratory compensation point (RCP). Participants were genotyped and divided
      into terciles based on the analysed variables. Genotype frequencies were compared
      through chi(2) test between lower and higher terciles, with the lowest or highest
      values of each analysed variable. ACTN3 XX genotype was over-represented in
      higher tercile for VT and RCP. Odds ratio also showed significantly higher
      chances of XX individuals to be in higher tercile compared to RR (7.3) and RR +
      RX (3.5) for VT and compared to RR genotype (8.1) and RR + RX (3.4) for RCP.
      Thus, XX individuals could attain the VT and RCP at higher speeds, suggesting
      that they are able to sustain higher running speeds in lower exercise intensity
      domains. It could result in higher lipid acids oxidation, saving muscle glycogen
      and delaying the fatigue during prolonged exercises, which could be the advantage
      mechanism of this genotype to endurance performance. 

PMID- 25939606
TI  - Burgers Vector Analysis of Vertical Dislocations in Ge Crystals by Large-Angle
      Convergent Beam Electron Diffraction.
AB  - By transmission electron microscopy with extended Burgers vector analyses, we
      demonstrate the edge and screw character of vertical dislocations (VDs) in novel
      SiGe heterostructures. The investigated pillar-shaped Ge epilayers on
      prepatterned Si(001) substrates are an attempt to avoid the high defect densities
      of lattice mismatched heteroepitaxy. The Ge pillars are almost completely strain
      relaxed and essentially defect-free, except for the rather unexpected VDs. We
      investigated both pillar-shaped and unstructured Ge epilayers grown either by
      molecular beam epitaxy or by chemical vapor deposition to derive a general
      picture of the underlying dislocation mechanisms. For the Burgers vector analysis
      we used a combination of dark field imaging and large-angle convergent beam
      electron diffraction (LACBED). With LACBED simulations we identify ideally suited
      zeroth and second order Laue zone Bragg lines for an unambiguous determination of
      the three-dimensional Burgers vectors. By analyzing dislocation reactions we
      confirm the origin of the observed types of VDs, which can be efficiently
      distinguished by LACBED. The screw type VDs are formed by a reaction of perfect
      60 degrees  dislocations, whereas the edge types are sessile dislocations that
      can be formed by cross-slips and climbing processes. The understanding of these
      origins allows us to suggest strategies to avoid VDs. 

PMID- 25939607
TI  - Prevalence of pressure ulcers in Thai wheelchair users with chronic spinal cord
      injuries.
AB  - STUDY DESIGN: A cross-sectional study. OBJECTIVES: To study prevalence of
      pressure ulcers (PrUs), quality of life (QoL) and effect of wheelchair cushions
      used by Thai wheelchair users with chronic spinal cord injury (SCI). SETTING:
      Maharaj Hospital, Chiang Mai, Thailand. METHODS: Thai chronic SCI wheelchair
      users, aged over 18 years and non-ambulatory with ASIA impairment scale A, B or C
      were recruited. They completed the PrUs questionnaire and rated the EuroQoL-5D
      and their health status with a visual analog scale (VAS). Demographic data of
      each participant were extracted from medical records. The EQ-5D health states
      were transformed to utility scores by using the Thai algorithm and the prevalence
      of PrUs was reported. The EQ-5D, the utility scores and the health status VAS
      were compared between those with and without current PrUs and between those
      participants using foam and air-filled cushions. RESULTS: Of 129 participants,
      26.4% had current PrUs at the time of the study, 27.9% had healed PrUs and 45.7%
      never had PrUs. The median VAS score for health status was 70 (Q1=50, Q3=80).
      Based on the EQ-5D, only one dimension (anxiety/depression) was significantly
      different between those with and those without current PrUs (P=0.015). Those
      using an air-filled cushions had a mean utility score four times higher than of
      those using a foam cushion (0.131 vs. 0.032, P=0.089) but not statistically
      significant. CONCLUSIONS: PrUs are still prevalent among Thai wheelchair users
      with chronic SCI. Anxiety/depression is associated with current ulcers.

PMID- 25939608
TI  - Eradication of HIV-1 from CNS reservoirs: current strategies and future
      priorities.

PMID- 25939609
TI  - Abstracts from the 13th International Symposium on NeuroVirology : June 2-5,
      2015, San Diego, California, USA.

PMID- 25939610
TI  - Clinical Outcomes After Arthroscopic Hip Labral Repair Using Looped Versus
      Pierced Suture Techniques.
AB  - BACKGROUND: With an improved understanding of the importance of the labrum,
      labral repair is replacing labral debridement as a component of hip arthroscopy
      for femoroacetabular impingement. Labral repair can be performed by passing
      suture limbs either around (looped) or through (pierced) the labral tissue.
      PURPOSE: To determine whether there is any clinical difference between these
      different labral repair techniques. STUDY DESIGN: Cohort study; Level of
      evidence, 3. METHODS: A prospective data registry was queried for patients who
      underwent primary hip arthroscopy with labral repair from 2009 to 2011. Patients
      older than 18 years who had undergone labral repair were included in the study.
      Exclusion criteria included previous hip surgery, avascular necrosis, joint space
      less than 2 mm, and labral reconstruction or augmentation. Patients were grouped
      based upon the 3 labral repair techniques: looped, pierced, or combined.
      Statistical equivalence testing was performed to evaluate the primary outcome
      measure, the Hip Outcome Score-activities of daily living subscale (HOS-ADL).
      Other measures included the HOS-sport subscale (HOS-Sport), modified Harris hip
      score (mHHS), Short Form-12 (SF-12), Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC), and patient satisfaction with outcome (1-10 scale;
      10 = very satisfied). RESULTS: Preoperative scores improved in the looped group
      (HOS-ADL, from 68 to 91; mHHS, from 64 to 83; HOS-Sport, from 51 to 81; and
      WOMAC, from 23 to 9), the pierced group (HOS-ADL, from 64 to 89; mHHS, from 62 to
      83; HOS-Sport, from 46 to 77; and WOMAC, from 34 to 12), and the combined group
      (HOS-ADL, from 64 to 89; mHHS, from 63 to 83; HOS-Sport, from 52 to 79; and
      WOMAC, from 26 to 12). Median patient satisfaction in all groups was 9.0. The 3
      labral repair groups were shown to be statistically and clinically equivalent (P
      < .05) with respect to the validated HOS-ADL to within a clinically irrelevant
      threshold at mean 36-month follow-up. In addition, there were no differences in
      secondary outcome measures or in the revision rate (looped, 7% [14/209], pierced,
      8% [5/65], and combined, 6% [5/83]). CONCLUSION: This study showed equivalent HOS
      ADL outcomes between looped, pierced, and combined labral repairs. Secondary
      outcome measures, including failure and revision rates, were not significantly
      different among the groups. Thus, suture type did not influence outcomes.

PMID- 25939611
TI  - Effect of Anterior Capsular Laxity on Horizontal Abduction and Forceful Internal
      Impingement in a Cadaveric Model of the Throwing Shoulder.
AB  - BACKGROUND: Excessive anterior capsular laxity (elongation of the anterior
      capsular ligaments) causes shoulder subluxation during acceleration of the
      throwing motion, leading to a disabled throwing shoulder. Few biomechanical
      studies have investigated the relationship between anterior capsular laxity and
      internal impingement, another cause of the disabled throwing shoulder.
      PURPOSE/HYPOTHESIS: The purpose of this study was to assess the effect of
      anterior capsular laxity on forceful internal impingement during the late cocking
      phase. The hypothesis was that excessive anterior shoulder laxity caused by
      elongation of the anterior capsular ligaments will increase the horizontal
      abduction angle to increase glenohumeral contact pressure. STUDY DESIGN:
      Controlled laboratory study. METHODS: Eight fresh-frozen cadaveric shoulders were
      tested with the shoulder abducted to 90 degrees  and at maximal external rotation
      to simulate the late cocking phase of the throwing motion. The angle of external
      rotation, anterior translation, angle of horizontal abduction, locations of the
      articular insertion of the rotator cuff tendons (supraspinatus and infraspinatus)
      on the greater tuberosity relative to the glenoid, and the glenohumeral contact
      pressure and area during internal impingement were measured. All data were
      compared between intact and elongated anterior capsule, which was created by
      repeatedly applying external rotational stretching. RESULTS: Elongation of the
      anterior capsular ligaments was confirmed by the increase in glenohumeral
      external rotation and anterior translation after our stretching technique.
      Location data showed that the posterior half of supraspinatus tendon, the entire
      infraspinatus tendon, and the posterosuperior labrum were impinged between the
      greater tuberosity and glenoid. Maximal glenohumeral horizontal abduction (2.2%
      increase; P = .003) and glenohumeral contact pressure (27.3% increase; P = .04)
      were significantly increased in the shoulder joint with increased anterior
      capsular laxity as compared with the intact condition. CONCLUSION: Increased
      anterior capsular laxity created by applying repetitive excessive external
      rotational torque significantly increased horizontal abduction and contact
      pressure in the glenohumeral joint. Concurrently, the supraspinatus and
      infraspinatus tendons and posterosuperior labrum were impinged between the
      greater tuberosity and glenoid. CLINICAL RELEVANCE: Increased anterior capsular
      laxity may exacerbate forceful internal impingement during the late cocking phase
      of the throwing motion.

PMID- 25939612
TI  - Sex Influences the Biomechanical Outcomes of Anterior Cruciate Ligament
      Reconstruction in a Preclinical Large Animal Model.
AB  - BACKGROUND: The risk of anterior cruciate ligament (ACL) injury is 2 to 10 times
      greater in women than men. While the effect of sex on injury risk is well
      established, its effects on surgical outcomes remain controversial.
      PURPOSE/HYPOTHESIS: To investigate whether the biomechanical outcomes of ACL
      reconstruction are affected by sex using an established porcine model that
      displays similar sex-specific differences in knee anatomy and ligament structural
      properties to humans. The hypothesis was that there will be sex differences in
      ACL reconstruction outcomes with regard to the graft structural properties, knee
      laxity, and cartilage damage. STUDY DESIGN: Controlled laboratory study. METHODS:
      A total of 41 adolescent Yucatan minipigs (23 male, 18 female) underwent
      unilateral ACL transection and ACL reconstruction using sex-matched bone-patellar
      tendon-bone allografts (with or without additional bioenhancement). Graft
      biomechanical and histological properties, knee laxity, and cartilage damage were
      assessed after 15 weeks. A 2-factor analysis of variance was used to investigate
      the effect of sex on all the measured outcomes after adjusting for the treatment
      effect. RESULTS: After 15 weeks of healing, female pigs had a significantly lower
      mean normalized graft yield load (by 18.5% +/- 7.7%; P = .023) and linear
      stiffness (by 11.9% +/- 5.6%; P = .043) compared with male pigs. Female pigs had
      significantly greater side-to-side differences in anteroposterior knee laxity at
      30 degrees  (by 1.4 +/- 0.6 mm; P = .028) and 90 degrees  (by 1.8 +/- 0.8 mm; P =
      .032). Female pigs had a lower graft vascular density (by 0.8 +/- 0.3 [analog
      scoring]; P = .021) with similar cellular and collagen-based histologic scores in
      both sexes (P > .6). Female pigs also had a significantly larger area of
      cartilage damage (by 43.3 +/- 14.8 mm(2); P = .014) after conventional ACL
      reconstruction compared with their male counterparts. CONCLUSION: Female pigs had
      significantly worse outcomes (ie, graft structural properties, knee laxity, and
      cartilage damage) compared with male pigs in this translational model after 15
      weeks of healing. CLINICAL RELEVANCE: These data suggest that further
      optimization of ACL injury treatments may be needed to accommodate each sex
      instead of using a "one fits all" approach to improve surgical outcomes, decrease
      incidence of reinjury, and decrease posttraumatic osteoarthritis risk after ACL
      reconstruction.

PMID- 25939613
TI  - Overestimate of the Incidence of Knee Osteoarthritis One Year After Anterior
      Cruciate Ligament Reconstruction? Comment on the Article by Culvenor et al.

PMID- 25939615
TI  - Monitoring pattern formation in drying and wetting dispersions of gold
      nanoparticles by ESEM.
AB  - We report an investigation of the self-assembly of patterns from functionalized
      gold nanoparticles (GNPs) by monitoring the process in situ by environmental
      scanning electron microscopy (ESEM) during both evaporation and condensation of
      the dispersant. As this method limits the choice of dispersants to water, GNPs
      functionalized with hydrophilic thiol ligands, containing poly(ethylene)glycol
      (PEG) groups, were used on a variety of substrates including pre-patterned ones.
      Particular emphasis was given to early stage deposition of GNPs, as well as
      redispersion and lift-off upon condensation of water droplets. ESEM presents a
      unique opportunity of directly imaging such events in situ. It was found that
      attractive interactions between the substrate and the GNPs are often stronger
      than expected once the particles have been deposited. The role of nickel
      perchlorate as a highly water-soluble additive was studied. It was found that
      entropically driven deposition of particles and decoration of surface features
      was enhanced in its presence, as expected. 

PMID- 25939614
TI  - Antipsychotic Augmentation of Serotonin Reuptake Inhibitors in Treatment
      Resistant Obsessive-Compulsive Disorder: An Update Meta-Analysis of Double-Blind,
      Randomized, Placebo-Controlled Trials.
AB  - BACKGROUND: Many patients with obsessive-compulsive disorder do not respond
      adequately to serotonin reuptake inhibitors. Augmentation with antipsychotic
      drugs can be beneficial in this regard. However, since new relevant randomized
      controlled trials evaluating new antipsychotics were conducted, a recalculation
      of the effect sizes appears necessary. METHODS: We meta-analyzed all double
      blind, randomized, placebo-controlled trials comparing augmentation of serotonin
      reuptake inhibitors with antipsychotics to placebo supplementation in treatment
      resistant obsessive-compulsive disorder. The primary outcome was mean change in
      the Yale-Brown Obsessive-Compulsive Scale total score. Secondary outcomes were
      obsessions, compulsions, response rates, and attrition rates. The data collection
      process was conducted independently by 2 authors. Hedges's g and risks ratios
      were calculated as effect sizes. In preplanned meta-regressions, subgroup
      analyses, and sensitivity analyses, we examined the robustness of the results and
      explored reasons for potential heterogeneity. RESULTS: Altogether, 14 double
      blind, randomized, placebo-controlled trials (n=491) investigating quetiapine
      (N=4, n=142), risperidone (N=4, n=132), aripiprazole (N=2, n=79), olanzapine
      (N=2, n=70), paliperidone (N=1, n=34), and haloperidol (N=1, n=34) were
      incorporated. Augmentation with antipsychotics was significantly more efficacious
      than placebo in Yale-Brown Obsessive-Compulsive Scale total reduction (N=14,
      n=478; Hedges's g=-0.64, 95% CI: -0.87 to -0.41; P=<.01). Aripiprazole (Hedges's
      g=-1.35), haloperidol (Hedges's g=-0.82), and risperidone (Hedges's g=-0.59)
      significantly outperformed placebo. Antipsychotics were superior to placebo in
      treating obsessions, compulsions, and achieving response. There was no between
      group difference concerning all-cause discontinuation. The nonsignificant meta
      regressions suggest no influence of the antipsychotic dose or baseline symptom
      severity on the meta-analytic results. CONCLUSIONS: According to our findings,
      antipsychotic augmentation of serotonin reuptake inhibitors can be regarded as an
      evidence-based measure in treatment-resistant obsessive-compulsive disorder.

PMID- 25939616
TI  - Dichlorocarbene-Functionalized Fluorographene: Synthesis and Reaction Mechanism.
AB  - Halogen functionalization of graphene is an important branch of graphene research
      as it provides opportunities to tailor the band gap and catalytic properties of
      graphene. Monovalent C-X bond obviates pitfalls of functionalization with atoms
      of groups 13, 15, and 16, which can introduce various poorly defined groups.
      Here, the preparation of functionalized graphene containing both fluorine and
      chlorine atoms is shown. The starting material, fluorographite, undergoes a
      reaction with dichlorocarbene to provide dichlorocarbene-functionalized
      fluorographene (DCC-FG). The material is characterized by X-ray photoelectron
      spectroscopy, Raman spectroscopy, and high-resolution transmission electron
      microscopy with X-ray dispersive spectroscopy. It is found that the chlorine
      atoms in DCC-FG are distributed homogeneously over the entire area of the
      fluorographene sheet. Further density functional theory calculations show that
      the mechanism of dichlorocarbene attack on fluorographene sheet is a two-step
      process. Dichlorocarbene detaches fluorine atoms from fluorographene sheet and
      subsequently adds to the newly formed sp(2) carbons. Halogenated graphene
      consisting of two (or eventually three) types of halogen atoms is envisioned to
      find its way as new graphene materials with tailored properties. 

PMID- 25939617
TI  - Post-infectious bronchiolitis obliterans and mannose-binding lectin insufficiency
      in Argentinean children.
AB  - BACKGROUND AND OBJECTIVE: Post-infectious bronchiolitis obliterans (PIBO) is a
      severe disorder following acute lower pulmonary infection in young children,
      especially caused by adenovirus. Mannose-binding lectin (MBL) deficiency arising
      from polymorphisms in the coding and non-coding region on the MBL2 gene has been
      associated with more frequent and severe respiratory infections. Our aim was to
      evaluate the influence of MBL variants in the susceptibility and evolution of
      children with PIBO. METHODS: One hundred eleven children with PIBO diagnosis were
      studied. The coding A, B, D and X promoter variants of MBL2 gene were assessed by
      PCR-RFLP. B and D alleles were pooled as O. The combined genotypes A/A and YA/O
      were grouped as sufficient MBL (sMBL), and O/O and XA/O as insufficient MBL
      (iMBL) groups. To evaluate the frequency of MBL2 polymorphisms in the general
      population, we studied DNA samples from 127 healthy donors from the blood bank of
      the hospital (control group). RESULTS: iMBL variants were significantly more
      frequent in PIBO children compared with controls (21.6% vs 10.2%, P = 0.01). PIBO
      patients with iMBL required intensive care unit (P = 0.001) and mechanical
      assistance at the moment of viral injury (P = 0.001) more frequently than those
      with sMBL. CONCLUSIONS: Insufficiency of MBL was more common in PIBO children
      than in healthy controls. This genetic condition was significantly associated
      with more severe initial disease, illustrating the relevance of innate immune
      defence factors prior to the maturation of the adaptative immune system.

PMID- 25939619
TI  - Non-convexly constrained image reconstruction from nonlinear tomographic X-ray
      measurements.
AB  - The use of polychromatic X-ray sources in tomographic X-ray measurements leads to
      nonlinear X-ray transmission effects. As these nonlinearities are not normally
      taken into account in tomographic reconstruction, artefacts occur, which can be
      particularly severe when imaging objects with multiple materials of widely
      varying X-ray attenuation properties. In these settings, reconstruction
      algorithms based on a nonlinear X-ray transmission model become valuable. We here
      study the use of one such model and develop algorithms that impose additional non
      convex constraints on the reconstruction. This allows us to reconstruct
      volumetric data even when limited measurements are available. We propose a
      nonlinear conjugate gradient iterative hard thresholding algorithm and show how
      many prior modelling assumptions can be imposed using a range of non-convex
      constraints. 

PMID- 25939618
TI  - Intracardiac thrombosis during liver transplant: A 17-year single-institution
      study.
AB  - Intracardiac thrombosis (ICT) during orthotopic liver transplantation (OLT) is an
      uncommon event. However, it is a devastating complication with high mortality
      when it occurs. This study aimed to identify possible predisposing factors for
      ICT during OLT. We retrospectively identified the cases of all patients with ICT
      during OLT at our institution from 1998 to 2014. Of 2750 OLTs performed, 10
      patients had ICT intraoperatively. The patients' immediate prethrombosis
      intraoperative hemodynamic and coagulation values and thromboelastography (TEG)
      data were reviewed. Preexisting venous thrombosis, atrial fibrillation, and the
      prior placement of a transjugular intrahepatic portosystemic shunt for portal
      hypertension were noted in several patients and may be related to ICT during OLT.
      A high Model of End-Stage Liver Disease score, low cardiac output, and sepsis did
      not appear to be associated with ICT. ICT occurred in some patients without the
      administration of antifibrinolytic agents. TEG and coagulation parameters did not
      appear to be helpful in predicting the onset of ICT. Four patients had ICT in
      both right- and left-sided heart chambers; none of these 4 patients survived. All
      6 patients with only right-sided thrombus survived. In those who survived,
      improved hemodynamics and clot disappearance on transesophageal echocardiography
      (TEE) occurred over time, even without the use of thrombolytics. Whether this is
      because of endogenous thrombolysis or distal clot propagation into the pulmonary
      vasculature, or both, is unclear. Tissue plasminogen activator may have a role in
      the resuscitation procedure. In conclusion, without the routine use of TEE during
      OLT, the incidence of ICT will remain an under-recognized event.

PMID- 25939621
TI  - Employing temporal self-similarity across the entire time domain in computed
      tomography reconstruction.
AB  - There are many cases where one needs to limit the X-ray dose, or the number of
      projections, or both, for high frame rate (fast) imaging. Normally, it improves
      temporal resolution but reduces the spatial resolution of the reconstructed data.
      Fortunately, the redundancy of information in the temporal domain can be employed
      to improve spatial resolution. In this paper, we propose a novel regularizer for
      iterative reconstruction of time-lapse computed tomography. The non-local penalty
      term is driven by the available prior information and employs all available
      temporal data to improve the spatial resolution of each individual time frame. A
      high-resolution prior image from the same or a different imaging modality is used
      to enhance edges which remain stationary throughout the acquisition time while
      dynamic features tend to be regularized spatially. Effective computational
      performance together with robust improvement in spatial and temporal resolution
      makes the proposed method a competitive tool to state-of-the-art techniques. 

PMID- 25939620
TI  - How little data is enough? Phase-diagram analysis of sparsity-regularized X-ray
      computed tomography.
AB  - We introduce phase-diagram analysis, a standard tool in compressed sensing (CS),
      to the X-ray computed tomography (CT) community as a systematic method for
      determining how few projections suffice for accurate sparsity-regularized
      reconstruction. In CS, a phase diagram is a convenient way to study and express
      certain theoretical relations between sparsity and sufficient sampling. We adapt
      phase-diagram analysis for empirical use in X-ray CT for which the same
      theoretical results do not hold. We demonstrate in three case studies the
      potential of phase-diagram analysis for providing quantitative answers to
      questions of undersampling. First, we demonstrate that there are cases where X
      ray CT empirically performs comparably with a near-optimal CS strategy, namely
      taking measurements with Gaussian sensing matrices. Second, we show that, in
      contrast to what might have been anticipated, taking randomized CT measurements
      does not lead to improved performance compared with standard structured sampling
      patterns. Finally, we show preliminary results of how well phase-diagram analysis
      can predict the sufficient number of projections for accurately reconstructing a
      large-scale image of a given sparsity by means of total-variation regularization.

PMID- 25939622
TI  - Scatter analysis and correction for ultrafast X-ray tomography.
AB  - Ultrafast X-ray computed tomography (CT) is an imaging technique with high
      potential for the investigation of the hydrodynamics in multiphase flows. For
      correct determination of the phase distribution of such flows, a high accuracy of
      the reconstructed image data is essential. In X-ray CT, radiation scatter may
      cause disturbing artefacts. As the scattering is not considered in standard
      reconstruction algorithms, additional methods are necessary to correct the
      detector readings or to prevent the detection of scattered photons. In this
      paper, we present an analysis of the scattering background for the ultrafast X
      ray CT imaging system ROFEX at the Helmholtz-Zentrum Dresden-Rossendorf and
      propose a correction technique based on collimation and deterministic simulation
      of first-order scattering. 

PMID- 25939623
TI  - Level-set reconstruction algorithm for ultrafast limited-angle X-ray computed
      tomography of two-phase flows.
AB  - Tomographic image reconstruction is based on recovering an object distribution
      from its projections, which have been acquired from all angular views around the
      object. If the angular range is limited to less than 180 degrees  of parallel
      projections, typical reconstruction artefacts arise when using standard
      algorithms. To compensate for this, specialized algorithms using a priori
      information about the object need to be applied. The application behind this work
      is ultrafast limited-angle X-ray computed tomography of two-phase flows. Here,
      only a binary distribution of the two phases needs to be reconstructed, which
      reduces the complexity of the inverse problem. To solve it, a new reconstruction
      algorithm (LSR) based on the level-set method is proposed. It includes one force
      function term accounting for matching the projection data and one incorporating a
      curvature-dependent smoothing of the phase boundary. The algorithm has been
      validated using simulated as well as measured projections of known structures,
      and its performance has been compared to the algebraic reconstruction technique
      and a binary derivative of it. The validation as well as the application of the
      level-set reconstruction on a dynamic two-phase flow demonstrated its
      applicability and its advantages over other reconstruction algorithms. 

PMID- 25939624
TI  - Introduction: a brief overview of iterative algorithms in X-ray computed
      tomography.
AB  - This paper presents a brief overview of some basic iterative algorithms, and more
      sophisticated methods are presented in the research papers in this issue. A range
      of algebraic iterative algorithms are covered here including ART, SART and OS
      SART. A major limitation of the traditional iterative methods is their
      computational time. The Krylov subspace based methods such as the conjugate
      gradients (CG) algorithm and its variants can be used to solve linear systems of
      equations arising from large-scale CT with possible implementation using modern
      high-performance computing tools. The overall aim of this theme issue is to
      stimulate international efforts to develop the next generation of X-ray computed
      tomography (CT) image reconstruction software. 

PMID- 25939625
TI  - Motion-compensated cone beam computed tomography using a conjugate gradient least
      squares algorithm and electrical impedance tomography imaging motion data.
AB  - Cone beam computed tomography (CBCT) is an imaging modality that has been used in
      image-guided radiation therapy (IGRT). For applications such as lung radiation
      therapy, CBCT images are greatly affected by the motion artefacts. This is mainly
      due to low temporal resolution of CBCT. Recently, a dual modality of electrical
      impedance tomography (EIT) and CBCT has been proposed, in which the high temporal
      resolution EIT imaging system provides motion data to a motion-compensated
      algebraic reconstruction technique (ART)-based CBCT reconstruction software. High
      computational time associated with ART and indeed other variations of ART make it
      less practical for real applications. This paper develops a motion-compensated
      conjugate gradient least-squares (CGLS) algorithm for CBCT. A motion-compensated
      CGLS offers several advantages over ART-based methods, including possibilities
      for explicit regularization, rapid convergence and parallel computations. This
      paper for the first time demonstrates motion-compensated CBCT reconstruction
      using CGLS and reconstruction results are shown in limited data CBCT considering
      only a quarter of the full dataset. The proposed algorithm is tested using
      simulated motion data in generic motion-compensated CBCT as well as measured EIT
      data in dual EIT-CBCT imaging. 

PMID- 25939626
TI  - A high-throughput system for high-quality tomographic reconstruction of large
      datasets at Diamond Light Source.
AB  - Tomographic datasets collected at synchrotrons are becoming very large and
      complex, and, therefore, need to be managed efficiently. Raw images may have high
      pixel counts, and each pixel can be multidimensional and associated with
      additional data such as those derived from spectroscopy. In time-resolved
      studies, hundreds of tomographic datasets can be collected in sequence, yielding
      terabytes of data. Users of tomographic beamlines are drawn from various
      scientific disciplines, and many are keen to use tomographic reconstruction
      software that does not require a deep understanding of reconstruction principles.
      We have developed Savu, a reconstruction pipeline that enables users to rapidly
      reconstruct data to consistently create high-quality results. Savu is designed to
      work in an 'orthogonal' fashion, meaning that data can be converted between
      projection and sinogram space throughout the processing workflow as required. The
      Savu pipeline is modular and allows processing strategies to be optimized for
      users' purposes. In addition to the reconstruction algorithms themselves, it can
      include modules for identification of experimental problems, artefact correction,
      general image processing and data quality assessment. Savu is open source, open
      licensed and 'facility-independent': it can run on standard cluster
      infrastructure at any institution. 

PMID- 25939627
TI  - Maximum a posteriori estimation of crystallographic phases in X-ray diffraction
      tomography.
AB  - A maximum a posteriori approach is proposed for X-ray diffraction tomography for
      reconstructing three-dimensional spatial distribution of crystallographic phases
      and orientations of polycrystalline materials. The approach maximizes the a
      posteriori density which includes a Poisson log-likelihood and an a priori term
      that reinforces expected solution properties such as smoothness or local
      continuity. The reconstruction method is validated with experimental data
      acquired from a section of the spinous process of a porcine vertebra collected at
      the 1-ID-C beamline of the Advanced Photon Source, at Argonne National
      Laboratory. The reconstruction results show significant improvement in the
      reduction of aliasing and streaking artefacts, and improved robustness to noise
      and undersampling compared to conventional analytical inversion approaches. The
      approach has the potential to reduce data acquisition times, and significantly
      improve beamtime efficiency. 

PMID- 25939628
TI  - Computed tomographic beam-hardening artefacts: mathematical characterization and
      analysis.
AB  - This paper presents a mathematical characterization and analysis of beam
      hardening artefacts in X-ray computed tomography (CT). In the field of dental and
      medical radiography, metal artefact reduction in CT is becoming increasingly
      important as artificial prostheses and metallic implants become more widespread
      in ageing populations. Metal artefacts are mainly caused by the beam-hardening of
      polychromatic X-ray photon beams, which causes mismatch between the actual
      sinogram data and the data model being the Radon transform of the unknown
      attenuation distribution in the CT reconstruction algorithm. We investigate the
      beam-hardening factor through a mathematical analysis of the discrepancy between
      the data and the Radon transform of the attenuation distribution at a fixed
      energy level. Separation of cupping artefacts from beam-hardening artefacts
      allows causes and effects of streaking artefacts to be analysed. Various computer
      simulations and experiments are performed to support our mathematical analysis. 

PMID- 25939629
TI  - Error analysis of tomographic reconstructions in the absence of projection data.
AB  - Error estimates for tomographic reconstructions (using Fourier transform-based
      algorithm) are available for cases where projection data are available. These
      data are used for reconstructions with different filter functions and the
      reliability of these reconstructions can be checked as per guidelines of those
      error estimates. There are cases where projection data are large (in gigabytes or
      terabytes) so storage of these data becomes an issue. It leads to storing of only
      the reconstructed images. Error estimation in such cases is presented here.
      Second-level projection data are calculated from the given reconstructed images
      ('first-level' images). These 'second-level' data are now used to generate
      'second-level' reconstructed images. Different filter functions are employed to
      check the fidelity of these 'second-level' images. This inference is extended to
      first-level images in view of the characteristics of the convolution operator.
      This approach is validated with experimental data obtained by the X-ray micro-CT
      scanner installed at IIT Kanpur. Five specimens (of same material) have been
      scanned. Data are available in this case thus we have performed a comparative
      error estimate analysis for the 'first-level' reconstructions (data obtained from
      CT machine) and second-level reconstructions (data generated from first-level
      reconstructions). We observe that both approaches show similar outcome. It
      indicates that error estimates can also be applied to images when data are not
      available. 

PMID- 25939630
TI  - The wound healing response after implantation of a drug-eluting stent is impaired
      persistently in the long term.
AB  - A 70-year-old man underwent stent implantation for right coronary artery (RCA)
      lesions with a bare metal stent (BMS) and two sirolimus-eluting stents (SES).
      However, as both the BMS and SES stented sites developed restenosis after 13
      months, he underwent target lesion revascularization using directional coronary
      atherectomy (DCA). On histopathology, the restenosis lesion at the SES-deployed
      site showed greater inflammation and less re-endothelialization than that at the
      BMS-deployed site. Three months later, the SES-deployed site developed a second
      restenosis, in which paclitaxel-eluting stents (PES) were implanted (PES-in-SES),
      while the BMS-deployed site was restenosis free. Five years later, restenosis was
      absent in these RCA lesions. However, by optical coherence tomography and/or
      coronary angioscopy, the PES-in-SES site in the RCA showed poor neointimal
      coverage over the stent struts and yellowish neointima, suggesting lipid-rich
      neoatheroma formation, whereas at the BMS site appropriate white neointima
      formation was observed. Drug-eluting stents still have problems of persistent
      inflammation, inappropriate neointima formation, and neoatherosclerosis. Although
      we are now in the era of second generation DESs in which better stent performance
      would be promising, we should remember that we are obliged to continue to follow
      up all patients in whom first generation DESs such as SES or PES have been
      placed. 

PMID- 25939631
TI  - Potassium induced contraction of the internal thoracic artery in vitro is time
      related: the potential consequences in the analysis of the mechanism of the spasm
      after coronary artery bypass grafting and in the analysis of the results of in
      vitro studies.
AB  - The aim of the present study was to examine how, under in vitro conditions, the
      human left internal thoracic artery (LITA) reacts to contractile
      agonist:potassium chloride (KCL) as a function of time, as well as to examine
      whether a change in the LITA reactivity can correlate with the occurrence of the
      refractory vascular spasm (RVS). Distal segments of LITA obtained from 33
      patients aged 38-73, at the time of routine coronary artery surgical
      revascularization (CABG). Contractile response to 80 mmol K(+) was recorded under
      isometric conditions. In 16 (48,5 %) LITA segments, contractile reaction to K(+)
      after experiments ranging 1-10 h were registered. No contractile response even
      after 10 h of incubation was observed in 17 (51.5 %) LITA segments. Between 120
      and 300 min after the beginning of the experiment, the reaction was maximum and
      amounted up to 300 % control reaction, then decreased. First, with respect to in
      vitro research isolated by LITA rings, while analyzing the results of the
      research, one should take into consideration the possibility that during the
      research, the functional state of the tissues changes and in particular its
      sensitivity to depolarization of the cell membrane. Second, the change in the
      sensitivity to depolarization of the cell membrane of the smooth muscles' LITA
      might be the potential mechanism causing the occurrence of the postoperative
      spasm after the CABG treatment.

PMID- 25939633
TI  - Electrokinetic Size and Mobility Traps for On-site Therapeutic Drug Monitoring.
AB  - The extraction of target analytes from biological samples is a bottleneck in
      analysis. A microfluidic device featuring an electrokinetic size and mobility
      trap was formed by two nanojunctions of different pore size to extract and
      concentrate analytical targets from complex samples. The trap was seamlessly
      coupled with electrophoretic separation for quantitative analysis. The device was
      applied to the analysis of ampicillin levels in blood within 5 min and a linear
      response over the range of 2.5-20 MUg mL(-1). This covers the recommended levels
      for treating sepsis, a critical condition with 30 to 50% mortality and
      unpredicted drug levels. The device provides a new opportunity for on-site
      therapeutic drug monitoring, which should enable quick and accurate dosing and
      may save lives in such critical conditions.

PMID- 25939632
TI  - Infants' grip strength predicts mu rhythm attenuation during observation of
      lifting actions with weighted blocks.
AB  - Research has established that the body is fundamentally involved in perception:
      bodily experience influences activation of the shared neural system underlying
      action perception and production during action observation, and bodily
      characteristics influence perception of the spatial environment. However, whether
      bodily characteristics influence action perception and its underlying neural
      system is unknown, particularly in early ontogeny. We measured grip strength in
      12-month-old infants and investigated relations with mu rhythm attenuation, an
      electroencephalographic correlate of the neural system underlying action
      perception, during observation of lifting actions performed with differently
      weighted blocks. We found that infants with higher grip strength exhibited
      significant mu attenuation during observation of lifting actions, whereas infants
      with lower grip strength did not. Moreover, a progressively strong relation
      between grip strength and mu attenuation during observation of lifts was found
      with increased block weight. We propose that this relation is attributable to
      differences in infants' ability to recognize the effort associated with lifting
      objects of different weights, as a consequence of their developing strength.
      Together, our results extend the body's role in perception by demonstrating that
      bodily characteristics influence action perception by shaping the activation of
      its underlying neural system. 

PMID- 25939634
TI  - Risk of skin ulcerations associated with oral nicorandil therapy: a population
      based study.
AB  - BACKGROUND: Although healthcare products regulatory agencies have issued warnings
      on risk of ulceration associated with the use of nicorandil, a population-based
      study has not been carried out. OBJECTIVES: To determine the relationship between
      use of nicorandil and skin ulceration. METHODS: We carried out a population-based
      study using a cohort of 1 million people assembled from Taiwan's national health
      insurance database. The association between nicorandil use and skin ulcers was
      estimated by a Cox proportional hazards regression model adjusting for a
      nicorandil-specific propensity score (PS) comprising of 86 potential predictors
      (c-statistic = 0.91). RESULTS: The prospective cohort was longitudinally followed
      from January 2005 to December 2009, during which 1268 new users of nicorandil and
      771 136 nonusers were identified. A higher frequency of skin ulcers (29 of 1268;
      2.3%) was observed for users of nicorandil compared with nonusers (3231 of 771
      136; 0.4%). Compared with nonusers, the crude hazard ratio (HR) associating
      nicorandil use with skin ulcers was 5.52 [95% confidence interval (CI) 3.82-7.95]
      and the PS-adjusted HR was 1.85 (95% CI 1.27-2.69). A risk period analysis showed
      that the risk of skin ulceration among users of nicorandil was greatest in the
      first year. Subgroup analysis found that the interaction term reached statistical
      significance (P < 0.05) for age and diabetes. CONCLUSIONS: Use of nicorandil was
      found to be associated with an increased risk for skin ulceration, especially in
      the first year after incident exposure. We suggest that regulatory agencies re
      evaluate the risk for skin ulceration associated with use of nicorandil.

PMID- 25939635
TI  - The interferon receptor-1 promoter polymorphisms affect the outcome of Caucasians
      with HBeAg-negative chronic HBV infection.
AB  - BACKGROUND & AIMS: The outcome of HBeAg-negative chronic hepatitis B virus (HBV)
      patients who may remain in the inactive carrier state (IC) or progress to HBeAg
      negative chronic hepatitis B may be affected by the host genetic profile. Genetic
      polymorphisms within not only the promoter but also the coding sequence of the
      interferon receptor 1 (INFAR1) gene have been associated with susceptibility to
      chronic HBV infection, but their role on the outcomes of HBeAg-negative patients
      has not been evaluated. We examined the association of INFAR1 promoter
      polymorphisms with the phase of chronic HBV infection in a demographically
      characterized Caucasian cohort of 183 consecutive HBeAg-negative chronic HBV
      patients. METHODS: Using a combination of conventional and allele-specific
      polymerase chain reactions, bidirectional sequencing and DNA-fragment analysis,
      we performed typing of three Single Nucleotide Polymorphisms (SNPs -568G/C, 
      408C/T, -3C/T) and one Variable Number Tandem Repeat [VNTR -77(GT)n] within the
      INFR1 promoter sequence. RESULTS: The genetic polymorphisms examined were found
      to be associated with the phase of HBeAg-negative chronic HBV patients. Using a
      multiple logistic regression model adjusting for age, gender and origin of the
      individuals, we found that patients with linked genotypes -408CT_-3CT were more
      likely to be ICs (OR = 2.42 vs. CC, P = 0.036). Also, given the partial linkage
      between SNP -568G/C and VNTR -77(GT)n, we found that linked genotypes -77(GT)n <=
      8/<=8_-568GC and -77(GT)n <= 8/<=8_-568CC were detected more frequently among ICs
      (OR = 11.69, P = 0.005 and OR = 7.56, P = 0.001 vs. -77(GT)n >8/>8_-568GG
      respectively). CONCLUSIONS: These findings suggest that these genetic variations
      represent important factors associated with the clinical phase of HBeAg-negative
      chronic HBV infection.

PMID- 25939636
TI  - High-Resolution Imaging of the Optic Nerve and Retina in Optic Nerve Hypoplasia.
AB  - PURPOSE: To investigate the optic nerve and macular morphology in patients with
      optic nerve hypoplasia (ONH) using spectral-domain optical coherence tomography
      (SD OCT). DESIGN: Prospective, cross-sectional, observational study. SUBJECTS: A
      total of 16 participants with ONH (10 female and 6 male; mean age, 17.2 years; 6
      bilateral involvement) and 32 gender-, age-, ethnicity-, and refraction-matched
      healthy controls. METHODS: High-resolution SD OCT (Copernicus [Optopol Technology
      S.A., Zawiercie, Poland], 3 MUm resolution) and handheld SD OCT (Bioptigen Inc
      [Research Triangle Park, NC], 2.6 MUm resolution) devices were used to acquire
      horizontal scans through the center of the optic disc and macula. MAIN OUTCOME
      MEASURES: Horizontal optic disc/cup and rim diameters, cup depth, peripapillary
      retinal nerve fiber layer (RNFL), and thickness of individual retinal layers in
      participants with ONH and in controls. RESULTS: Patients with ONH had
      significantly smaller discs (P < 0.03 and P < 0.001 compared with unaffected eye
      and healthy controls, respectively), horizontal cup diameter (P < 0.02 for both),
      and cup depth (P < 0.02 and P < 0.01, respectively). In the macula, significantly
      thinner RNFL (nasally), ganglion cell layer (GCL) (nasally and temporally), inner
      plexiform layer (IPL) (nasally), outer nuclear layer (ONL) (nasally), and inner
      segment (centrally and temporally) were found in patients with ONH compared with
      the control group (P < 0.05 for all comparisons). Continuation of significantly
      thicker GCL, IPL, and outer plexiform layer in the central retinal area (i.e.,
      foveal hypoplasia) was found in more than 80% of patients with ONH. Clinically
      unaffected fellow eyes of patients with ONH showed mild features of
      underdevelopment. Visual acuity and presence of septo-optic dysplasia were
      associated with changes in GCL and IPL. Sensitivity and specificity for the
      detection of ONH based on disc and retinal optical coherence tomography (OCT)
      parameters were >80%. CONCLUSIONS: Our study provides evidence of retinal changes
      in ONH. In addition to thinning of retina layers mainly involving the RNFL and
      GCL, signs reminiscent of foveal hypoplasia were observed in patients with ONH.
      Optic nerve and foveal parameters measured using OCT showed high sensitivity and
      specificity for detecting ONH, demonstrating their useful for clinical diagnosis.

PMID- 25939637
TI  - A novel approach for building up infraoccluded ankylosed primary molars in cases
      of missing premolars: A case report.
AB  - BACKGROUND: In cases of infraoccluded primary molars associated with agenesis of
      premolars, any treatment plan occasionally includes retention of the primary
      teeth for space preservation and future implant placement if needed. In these
      cases, building up the crowns to the occlusal line is necessary to prevent
      various clinical problems. The present case report describes in detail a novel
      but simple clinical approach for retention and building up of the crown of
      infraoccluded primary molars. CASE REPORT/TECHNIQUE PRESENTATION: The technique
      is presented in a 14-year-old girl with nine missing permanent teeth. Orthodontic
      evaluation indicated space closure for five teeth and space maintenance in the
      remaining four second primary molars, three of them being infraoccluded. The
      technique included the following clinical steps: (a) elastic separators were
      placed proximally to the primary molars for few days to create space; (b)
      proximal minimal reduction of the crown width was performed; a direct hand
      composite resin core was made to increase crown height facilitating the selection
      of a preformed metal crown (PMC). The selected PMC was filled with self-curing
      composite resin and placed on the primary tooth following an acid etch and
      adhesive procedure; excess cervical material was removed; (c) after
      polymerisation, the PMC was carefully removed using cutting and hand instruments,
      revealing the composite resin fabricated crown which was adjusted for occlusion
      and polished. Radiographic evaluation confirmed the result. CONCLUSION: This
      simple method for infraoccluded primary molars crown building up to occlusion
      using conventional instruments and materials, appears to be a valuable clinical
      tool for paediatric dentists who frequently find themselves dealing with primary
      teeth that need to be retained and which can produce serious clinical problems if
      left untreated.

PMID- 25939638
TI  - A comparison of the sedative effect of oral versus nasal midazolam combined with
      nitrous oxide in uncooperative children.
AB  - AIM: To compare a combination of oral midazolam (0.2 mg/kg body weight) and
      nitrous oxide-oxygen sedation with a combination of intranasal midazolam (0.1
      mg/kg body weight) and nitrous oxide-oxygen sedation for effectiveness, patient
      acceptability and safety profile in controlling the behaviour of uncooperative
      children. METHODS: Thirty children, 4-10 years of age, referred for dental
      treatment were included in the study with a crossover design. Each patient was
      sedated with a combination of either oral midazolam and nitrous oxide-oxygen
      sedation or intranasal midazolam and nitrous oxide-oxygen sedation at subsequent
      dental treatment visits. During the treatment procedure, the study recorded
      scales for drug acceptability, onset of sedation, acceptance of nasal mask,
      sedation, behavioural, safety, overall behaviour and alertness. RESULTS: The
      grade of acceptability of midazolam in both groups was consistently good. There
      was a significant difference (p < 0.001) in the time of onset of sedation, which
      was significantly quicker with the intranasal administration of midazolam. The
      mean time of onset for oral midazolam was 20.1 (17-25) min and for intranasal
      midazolam 12.1 (8-18) min. The efficacy profile of the present study included:
      acceptance of nasal mask, sedation score, crying levels, motor movements and
      overall behaviour scores. The results did not show any statistically significant
      differences. All the parameters were highly satisfactory. The difference in
      alertness was statistically significant (p value <0.05), being higher in the
      intranasal group than the oral group and suggestive of faster recovery using
      intranasal midazolam. CONCLUSION: The intranasal route of midazolam
      administration has a quick onset of action and a quick recovery of the patient
      from sedation as compared to the oral route of midazolam administration.
      Midazolam administered through the intranasal route is as effective as the oral
      route at a lower dosage. Therefore, it is an effective alternative to oral route
      for a paediatric dental situation.

PMID- 25939639
TI  - Ventilation/perfusion SPECT or SPECT/CT for lung function imaging in patients
      with pulmonary emphysema?
AB  - PURPOSE: To evaluate the utility of attenuation correction (AC) of V/P SPECT
      images for patients with pulmonary emphysema. MATERIALS AND METHODS: Twenty-one
      patients (mean age 67.6 years) with pulmonary emphysema who underwent V/P
      SPECT/CT were included. AC/non-AC V/P SPECT images were compared visually and
      semiquantitatively. Visual comparison of AC/non-AC images was based on a 5-point
      likert scale. Semiquantitative comparison assessed absolute counts per lung
      (aCpLu) and lung lobe (aCpLo) for AC/non-AC images using software-based analysis;
      percentage counts (PC = (aCpLo/aCpLu) * 100) were calculated. Correlation between
      AC/non-AC V/P SPECT images was analyzed using Spearman's rho correlation
      coefficient; differences were tested for significance with the Wilcoxon rank sum
      test. RESULTS: Visual analysis revealed high conformity for AC and non-AC V/P
      SPECT images. Semiquantitative analysis of PC in AC/non-AC images had an
      excellent correlation and showed no significant differences in perfusion (rho =
      0.986) or ventilation (rho = 0.979, p = 0.809) SPECT/CT images. CONCLUSION: AC of
      V/P SPECT images for lung lobe-based function imaging in patients with pulmonary
      emphysema do not improve visual or semiquantitative image analysis.

PMID- 25939640
TI  - Prognostic value of semi-quantitative tumor uptake on Tc-99m sestamibi breast
      specific gamma imaging in invasive ductal breast cancer.
AB  - OBJECTIVES: This study investigated the prognostic value of preoperative breast
      specific gamma imaging (BSGI) uptake measured by a semi-quantitative method in
      invasive ductal carcinoma (IDC). METHODS: One hundred and sixty-two women with
      IDC who underwent preoperative BSGI were retrospectively enrolled. The tumor-to
      normal tissue ratio (TNR) was measured on BSGI and correlated with histologic
      prognostic factors. The prognostic impact of TNR was tested with regard to
      progression-free survival (PFS) and compared with established prognostic factors.
      RESULTS: High TNR was significantly correlated with tumor size >2 cm (p < 0.001),
      high nuclear grade (p = 0.04), high histologic grade (p = 0.01), axillary node
      positivity (p = 0.04), ER negativity (p = 0.03), HER2 positivity (p = 0.01), and
      high MIB-1 index (p = 0.001). Among 162 patients, 14 experienced recurrence
      during mean follow-up time of 34.7 +/- 14.9 months. In Kaplan-Meier survival
      analyses, high TNR (p < 0.001), high nuclear grade (p = 0.02), high histologic
      grade (p = 0.007), ER/PR negativity (p = 0.003 and p < 0.001, respectively), HER2
      positivity (p = 0.01), triple negativity (p = 0.02), and high MIB-1 index (p =
      0.02) showed a significant relationship with poor prognosis. Among them, high TNR
      was an independent poor prognostic factor in a multivariate regression analysis
      (p = 0.01). CONCLUSIONS: High BSGI uptake measured by a semi-quantitative method
      was correlated with diverse poor histologic prognostic factors and was an
      independent poor prognostic factor in invasive ductal cancer.

PMID- 25939641
TI  - Development of atraumatic heel-stick procedures by combined treatment with non
      nutritive sucking, oral sucrose, and facilitated tucking: a randomised,
      controlled trial.
AB  - BACKGROUND: Preterm infants manifest pain and stress by behavioural agitation and
      state change. Few studies have explored the effects of combining
      nonpharmacological interventions, i.e. non-nutritive sucking, oral sucrose, and
      facilitated tucking, on infants' behaviours across painful procedures.
      OBJECTIVES: To explore the effects of combined use of three nonpharmacological
      interventions (non-nutritive sucking, oral sucrose, and facilitated tucking) on
      infants' pain- and stress-related behaviours during four assessment phases:
      baseline, intervention, heel stick, and recovery. DESIGN: Prospective, randomised
      controlled trial. SETTING: Level III neonatal intensive care unit in Taipei.
      METHOD: A convenience sample of 110 infants (gestational age 27-37 weeks) needing
      heel sticks was randomly assigned to five combinations of nonpharmacological
      treatments: (1) routine care, (2) non-nutritive sucking+facilitated tucking, (3)
      oral sucrose+facilitated tucking, (4) non-nutritive sucking+oral sucrose, and (5)
      non-nutritive sucking+oral sucrose+facilitated tucking. Outcomes were infants'
      withdrawal or stress (grimace, limb and trunk extension or squirming) and
      approach or self-soothing (sucking, sucking search, or mouthing; hand holding or
      grasping; and hand to mouth, face) behaviours. RESULTS: The frequency of infants'
      withdrawal behaviours decreased significantly when they received combinations of
      nonpharmacological interventions before heel stick. Specifically, grimace
      frequency decreased by 32.2%, 30.6%, 19.7%, and 13.8% in infants receiving oral
      sucrose+non-nutritive sucking+facilitated tucking, non-nutritive sucking+oral
      sucrose, oral sucrose+facilitated tucking, and non-nutritive sucking+facilitated
      tucking, respectively, compared to those receiving routine care across assessment
      phases. Furthermore, infants' frequency of limb and trunk extension or squirming
      decreased by 24.0% when they received non-nutritive sucking+oral
      sucrose+facilitated tucking compared to those receiving routine care. Infants'
      frequency of approach behaviours did not change significantly across all phases
      when they received non-nutritive sucking+oral sucrose+facilitated tucking, non
      nutritive sucking+oral sucrose, and oral sucrose+facilitated tucking compared to
      those receiving routine care. CONCLUSIONS: The combined use of nonpharmacological
      interventions (non-nutritive sucking+oral sucrose+facilitated tucking)
      effectively reduced the frequencies of infants' withdrawal behaviours, i.e.
      grimace and limb and trunk extension or squirming. Our results provide evidence
      supporting clinicians' incorporation of the combined use of facilitated tucking,
      oral sucrose, and non-nutritive sucking into clinical practice during painful
      procedures. Heel-stick procedures can be atraumatic when conducted while infants
      are stable and quiet, appropriately positioned, and stabilised and by offering
      facilitated tucking, oral sucrose, and non-nutritive sucking before gently
      sticking the heel and squeezing blood.

PMID- 25939642
TI  - Passive cigarette smoking changes the circadian rhythm of clock genes in rat
      intervertebral discs.
AB  - We aimed to elucidate the molecular changes in intervertebral discs (IVDs) caused
      by passive smoking. Rats were subjected to 8 weeks of passive smoking;
      thereafter, their lumbar vertebrae were harvested. The annulus fibrosus and
      cartilage endplate (AF/CEP) were harvested together, and the nucleus pulposus
      (NP) was isolated separately. The expression of 27,342 rat genes was analyzed. In
      3 "nonsmoking" rats, 96 of 112 genes whose expression varied >=10-fold between
      the AF/CEP and NP were more highly expressed in the AF/CEP. With these
      differentially expressed genes, we uncovered novel AF/CEP and NP marker genes and
      indicated their possible novel functions. Although passive smoking induced less
      marked alteration in the gene expression profiles of both the AF/CEP and NP,
      multiple clock-related genes showed altered expression. These genes were
      expressed with a circadian rhythm in IVD cells, and most genes showed a phase
      shift of -6 to -9 h induced by passive smoking. Some clock-related genes showed
      abolished oscillation in the NP. Passive smoking also changed the expression
      levels of proteases and protease inhibitors and reduced the expression of NP
      marker genes. Thus, passive smoking induces changes in the circadian rhythm of a
      peripheral clock (IVD clock) that might be involved in molecular events related
      to IVD degeneration.

PMID- 25939644
TI  - Effect of thematic map misclassification on landscape multi-metric assessment.
AB  - Advancements in remote sensing and computational tools have increased our
      awareness of large-scale environmental problems, thereby creating a need for
      monitoring, assessment, and management at these scales. Over the last decade,
      several watershed and regional multi-metric indices have been developed to assist
      decision-makers with planning actions of these scales. However, these tools use
      remote-sensing products that are subject to land-cover misclassification, and
      these errors are rarely incorporated in the assessment results. Here, we examined
      the sensitivity of a landscape-scale multi-metric index (MMI) to error from
      thematic land-cover misclassification and the implications of this uncertainty
      for resource management decisions. Through a case study, we used a simplified
      floodplain MMI assessment tool, whose metrics were derived from Landsat thematic
      maps, to initially provide results that were naive to thematic misclassification
      error. Using a Monte Carlo simulation model, we then incorporated map
      misclassification error into our MMI, resulting in four important conclusions:
      (1) each metric had a different sensitivity to error; (2) within each metric, the
      bias between the error-naive metric scores and simulated scores that incorporate
      potential error varied in magnitude and direction depending on the underlying
      land cover at each assessment site; (3) collectively, when the metrics were
      combined into a multi-metric index, the effects were attenuated; and (4) the
      index bias indicated that our naive assessment model may overestimate floodplain
      condition of sites with limited human impacts and, to a lesser extent, either
      over- or underestimated floodplain condition of sites with mixed land use. 

PMID- 25939643
TI  - Multifunctional biocompatible graphene oxide quantum dots decorated magnetic
      nanoplatform for efficient capture and two-photon imaging of rare tumor cells.
AB  - Circulating tumor cells (CTCs) are extremely rare cells in blood containing
      billions of other cells. The selective capture and identification of rare cells
      with sufficient sensitivity is a real challenge. Driven by this need, this
      manuscript reports the development of a multifunctional biocompatible graphene
      oxide quantum dots (GOQDs) coated, high-luminescence magnetic nanoplatform for
      the selective separation and diagnosis of Glypican-3 (GPC3)-expressed Hep G2
      liver cancer tumor CTCs from infected blood. Experimental data show that an anti
      GPC3-antibody-attached multifunctional nanoplatform can be used for selective Hep
      G2 hepatocellular carcinoma tumor cell separation from infected blood containing
      10 tumor cells/mL of blood in a 15 mL sample. Reported data indicate that,
      because of an extremely high two-photon absorption cross section (40530 GM), an
      anti-GPC3-antibody-attached GOQDs-coated magnetic nanoplatform can be used as a
      two-photon luminescence platform for selective and very bright imaging of a Hep
      G2 tumor cell in a biological transparency window using 960 nm light.
      Experimental results with nontargeted GPC3(-) and SK-BR-3 breast cancer cells
      show that multifunctional-nanoplatform-based cell separation, followed by two
      photon imaging, is highly selective for Hep G2 hepatocellular carcinoma tumor
      cells. 

PMID- 25939645
TI  - Natural radionuclide activities in forest soil horizons of Mount IDA/Kazdagi,
      Turkey.
AB  - Natural radioactivity distribution of (40)K, (238)U, and (232)Th isotopes in
      forest soils was investigated by using gamma-ray spectrometry. An extensive
      radioecological study was carried out between 2010 and 2013 in Mount IDA/Kazdagi,
      located in Edremit region in Turkey. A total of 341 soil samples were collected
      from the surface and organic horizons (OL, OF+OH, and A) in 118 soil profiles.
      The distributions of natural radioactivity levels in these horizons and
      corresponding absorbed dose rates from outdoors terrestrial gamma radiation
      throughout the region were mapped in detail. Mean (40)K activity values over the
      combined horizons varied between 43 and 1,008 Bq kg(-1); whereas, mean (226)Ra
      and (232)Th concentrations over the combined horizons ranged between 5-152 and 6
      275 Bq kg(-1), respectively. Our data indicate that the radioactivity values of
      the study sites were within the universal normal range. The significant variation
      among the (232)Th, (226)Ra, and (40)K activities and gamma dose rate might be due
      to the geological variation in the study sites.

PMID- 25939646
TI  - Quantitative determination of dimethyl fumarate in silica gel by solid-phase
      microextraction/gas chromatography/mass spectrometry and ultrasound-assisted
      extraction/gas chromatography/mass spectrometry.
AB  - Dimethyl fumarate (DMF) is a chemical compound which has been added to silica gel
      bags used for preserving leather products during shipment. DMF has recently been
      singled out due to its ability to induce a number of medical problems in people
      which touch products contaminated by it. Its use as a biocide has been recently
      made illegal in Europe. Two different extraction techniques, namely ultrasound
      assisted extraction (UAE) and solid-phase microextraction (SPME), both coupled
      with gas chromatography/mass spectrometry were applied to the quantitative
      determination of DMF in silica gel. Linearity of the methods, reproducibility and
      detection limits were determined. The two methods were applied to the
      quantification of DMF in thirty-four silica gel samples used as anti-mould agents
      in different leather products sold in Italy, and the obtained results were
      statistically compared. 

PMID- 25939647
TI  - Assessment of Fracture Risk in A Population of Postmenopausal Italian Women: A
      Comparison of Two Different Tools.
AB  - The main objective of this study was to compare in the assessment of risk of
      fractures in postmenopausal women two algorithms for 10-year fracture risk
      evaluation, the WHO-endorsed FRAX((r)) and the Italian FRAX-derived version
      (DeFRA), which considers BMD of different bone sites and allows the inclusion of
      other data. In a secondary analysis, we compared the performance of the tools in
      discriminating subjects who sustained previous major fractures from those who did
      not. The 10-year fracture risk score was evaluated in a sample of 989 climacteric
      women using FRAX and DeFRA tools. Bone mineral density was also included in the
      calculation of these algorithms. Comparing how the subjects were assigned to
      different risk classes by the two tools, we found that DeFRA attributed higher
      risk categories than FRAX, among women in the subgroups between 50 and 59 and,
      mostly, 60-69 years of age. ROC curve analysis showed that DeFRA had the same
      discriminative ability to identify previous major osteoporotic fractures compared
      to FRAX (AUC = 0.74 for both). If confirmed by prospective studies, our findings
      would suggest that DeFRA might be ascribed as at least equivalent to FRAX or
      perhaps slightly most appropriate in the categorization of the fracture risk,
      particularly in women aged 60-69 years, a period in which bone densitometry
      analysis is highly recommended.

PMID- 25939648
TI  - Bone Material Properties and Skeletal Fragility.
AB  - Deformations of vertebrae and sudden fractures of long bones caused by
      essentially normal loading are a characteristic problem in osteoporosis. If the
      loading is normal, then the explanation for and prediction of unexpected bone
      failure lies in understanding the mechanical properties of the whole bone-which
      come from its internal and external geometry, the mechanical properties of the
      hard tissue, and from how well the tissue repairs damage. Modern QCT and MRI
      imaging systems can measure the geometry of the mineralized tissue quite well in
      vivo-leaving the mechanical properties of the hard tissue and the ability of bone
      to repair damage as important unknown factors in predicting fractures. This
      review explains which material properties must be measured to understand why some
      bones fail unexpectedly despite our current ability to determine bone geometry
      and bone mineral content in vivo. Examples of how to measure the important
      mechanical properties are presented along with some analysis of potential
      drawbacks of each method. Particular attention is given to methods useful to
      characterize the loss of bone toughness caused by mechanical fatigue, drug side
      effects, and damage to the bone matrix. 

PMID- 25939649
TI  - Digoxin-associated mortality: a systematic review and meta-analysis of the
      literature.
AB  - There are conflicting data regarding the effect of digoxin use on mortality in
      patients with atrial fibrillation (AF) or with congestive heart failure (CHF).
      The aim of this meta-analysis was to provide detailed analysis of the currently
      available study reports. We performed a MEDLINE and a COCHRANE search (1993-2014)
      of the English literature dealing with the effects of digoxin on all-cause
      mortality in subjects with AF or CHF. Only full-sized articles published in peer
      reviewed journals were considered for this meta-analysis. A total of 19 reports
      were identified. Nine reports dealt with AF patients, seven with patients
      suffering from CHF, and three with both clinical conditions. Based on the
      analysis of adjusted mortality results of all 19 studies comprising 326 426
      patients, digoxin use was associated with an increased relative risk of all-cause
      mortality [Hazard ratio (HR) 1.21, 95% confidence interval (CI), 1.07 to 1.38, P
      < 0.01]. Compared with subjects not receiving glycosides, digoxin was associated
      with a 29% increased mortality risk (HR 1.29; 95% CI, 1.21 to 1.39) in the
      subgroup of publications comprising 235 047 AF patients. Among 91.379 heart
      failure patients, digoxin-associated mortality risk increased by 14% (HR 1.14,
      95% CI, 1.06 to 1.22). The present systematic review and meta-analysis of all
      available data sources suggest that digoxin use is associated with an increased
      mortality risk, particularly among patients suffering from AF. 

PMID- 25939650
TI  - The Accumulation of Deleterious Mutations as a Consequence of Domestication and
      Improvement in Sunflowers and Other Compositae Crops.
AB  - For populations to maintain optimal fitness, harmful mutations must be
      efficiently purged from the genome. Yet, under circumstances that diminish the
      effectiveness of natural selection, such as the process of plant and animal
      domestication, deleterious mutations are predicted to accumulate. Here, we
      compared the load of deleterious mutations in 21 accessions from natural
      populations and 19 domesticated accessions of the common sunflower using whole
      transcriptome single nucleotide polymorphism data. Although we find that genetic
      diversity has been greatly reduced during domestication, the remaining mutations
      were disproportionally biased toward nonsynonymous substitutions.
      Bioinformatically predicted deleterious mutations affecting protein function were
      especially strongly over-represented. We also identify similar patterns in two
      other domesticated species of the sunflower family (globe artichoke and cardoon),
      indicating that this phenomenon is not due to idiosyncrasies of sunflower
      domestication or the sunflower genome. Finally, we provide unequivocal evidence
      that deleterious mutations accumulate in low recombining regions of the genome,
      due to the reduced efficacy of purifying selection. These results represent a
      conundrum for crop improvement efforts. Although the elimination of harmful
      mutations should be a long-term goal of plant and animal breeding programs, it
      will be difficult to weed them out because of limited recombination. 

PMID- 25939651
TI  - Describing and Evaluating Novel Programs and Therapies for Older Persons.

PMID- 25939652
TI  - Cadmium translocation by contractile roots differs from that in regular, non
      contractile roots.
AB  - BACKGROUND AND AIMS: Contractile roots are known and studied mainly in connection
      with the process of shrinkage of their basal parts, which acts to pull the shoot
      of the plant deeper into the ground. Previous studies have shown that the
      specific structure of these roots results in more intensive water uptake at the
      base, which is in contrast to regular root types. The purpose of this study was
      to find out whether the basal parts of contractile roots are also more active in
      translocation of cadmium to the shoot. METHODS: Plants of the South African
      ornamental species Tritonia gladiolaris were cultivated in vitro for 2 months, at
      which point they possessed well-developed contractile roots. They were then
      transferred to Petri dishes with horizontally separated compartments of agar
      containing 50 umol Cd(NO3)2 in the region of the root base or the root apex.
      Seedlings of 4-d-old maize (Zea mays) plants, which do not possess contractile
      roots, were also transferred to similar Petri dishes. The concentrations of Cd in
      the leaves of the plants were compared after 10 d of cultivation. Anatomical
      analyses of Tritonia roots were performed using appropriately stained freehand
      cross-sections. KEY RESULTS: The process of contraction required specific
      anatomical adaptation of the root base in Tritonia, with less lignified and less
      suberized tissues in comparison with the subapical part of the root. These
      unusual developmental characteristics were accompanied by more intensive
      translocation of Cd ions from the basal part of contractile roots to the leaves
      than from the apical-subapical root parts. The opposite effects were seen in the
      non-contractile roots of maize, with higher uptake and transport by the apical
      parts of the root and lower uptake and transport by the basal part. CONCLUSIONS:
      The specific characteristics of contractile roots may have a significant impact
      on the uptake of ions, including toxic metals from the soil surface layers. This
      may be important for plant nutrition, for example in the uptake of nutrients from
      upper soil layers, which are richer in humus in otherwise nutrient-poor soils,
      and also has implications for the uptake of surface-soil pollutants.

PMID- 25939653
TI  - Childhood poverty and recruitment of adult emotion regulatory neurocircuitry.
AB  - One in five American children grows up in poverty. Childhood poverty has far
      reaching adverse impacts on cognitive, social and emotional development. Altered
      development of neurocircuits, subserving emotion regulation, is one possible
      pathway for childhood poverty's ill effects. Children exposed to poverty were
      followed into young adulthood and then studied using functional brain imaging
      with an implicit emotion regulation task focused. Implicit emotion regulation
      involved attention shifting and appraisal components. Early poverty reduced left
      dorsolateral prefrontal cortex recruitment in the context of emotional
      regulation. Furthermore, this emotion regulation associated brain activation
      mediated the effects of poverty on adult task performance. Moreover, childhood
      poverty also predicted enhanced insula and reduced hippocampal activation,
      following exposure to acute stress. These results demonstrate that childhood
      poverty can alter adult emotion regulation neurocircuitry, revealing specific
      brain mechanisms that may underlie long-term effects of social inequalities on
      health. The role of poverty-related emotion regulatory neurocircuitry appears to
      be particularly salient during stressful conditions. 

PMID- 25939654
TI  - Factors associated with physical or sexual intimate partner violence perpetration
      by men attending substance misuse treatment in Catalunya: A mixed methods study.
AB  - BACKGROUND: Prevalence of intimate partner violence perpetration is higher among
      male substance misusers than men in the general population. Previous studies have
      included few risk factors, limiting their capacity to inform interventions. AIM:
      The aim of this study was to examine factors associated with intimate partner
      violence by male substance misusers. METHODS: Two hundred and thirty-five men in
      treatment for substance misuse completed surveys that included the Revised
      Conflict Tactics Scale and the Psychological Maltreatment of Women Inventory
      (PMWI). Variables significant in bivariate analyses were entered into multiple
      logistic regression analyses. Seventeen in-depth interviews were conducted with
      perpetrators and analysed using a framework approach. RESULTS: Just over a third
      of the men (34%) had been violent in the last year to their current/most recent
      partner. After excluding the men's own domestic victimisation from the
      multivariate model, perpetratation of such violence was significantly and
      independently associated with lower level of education, having higher PMWI
      dominance-isolation and emotional-verbal subscale scores and parents who had
      separated/divorced, and at a lower level of significance, childhood physical
      abuse, hazardous drinking and cocaine as the principal drug for which treatment
      was sought. Interview data suggested that perpetrators 'blamed' alcohol or
      cocaine use, jealousy, control and provocation or 'fighting back' for their
      behaviour. CONCLUSIONS: Intimate partner violence is common among men attending
      substance misuse treatment. Integrated interventions should that address both
      intimate partner violence and substance misuse should be considered. Areas for
      intervention would include reducing dominating-isolating behaviours and emotional
      verbal abuse, improving communication skills, challenging gender-specific roles
      and believing that substance use 'causes' violent behaviour.

PMID- 25939655
TI  - Vascular and central hemodynamic changes following exercise-induced heat stress.
AB  - This study examined the effects of moderate exercise-induced heat stress (EIHS)
      on vascular function, central hemodynamic load and indices of coronary perfusion.
      Vascular-hemodynamic measures were collected in 12 healthy men (aged 22+/-3
      years) pre and post 100 minutes of moderate, intermittent exercise in two
      randomized conditions: heat stress (HS; wearing firefighter personal protective
      equipment (PPE)), and no heat stress (NHS; wearing a cooling shirt and equivalent
      PPE weight). Aortic blood pressure, reflected wave pressure (Pb), systolic (SPTI)
      and diastolic pressure time-integral (DPTI), and aortic stiffness were assessed
      before and after each condition. SPTI was significantly greater, and DPTI and Pb
      were significantly lower for HS-post compared to NHS-post (p<0.05). Pulse wave
      velocity was not different between conditions. In conclusion, EIHS does not
      affect aortic stiffness, but increases indices of myocardial work and reduces
      indices of coronary perfusion which may be related to chronotropic responses to
      EIHS. The mismatch between oxygen demand and oxygen supply may increase cardiac
      vulnerability to ischemia during strenuous work in the heat.

PMID- 25939656
TI  - Firefighting: can our arteries take the heat?

PMID- 25939657
TI  - Effect of aspirin on acute changes in peripheral arterial stiffness and
      endothelial function following exertional heat stress in firefighters: The
      factorial group results of the Enhanced Firefighter Rehab Trial.
AB  - Peripheral arterial stiffness and endothelial function, which are independent
      predictors of cardiac events, are abnormal in firefighters. We examined the
      effects of aspirin on peripheral arterial stiffness and endothelial function in
      firefighters. Fifty-two firefighters were randomized to receive daily 81 mg
      aspirin or placebo for 14 days before treadmill exercise in thermal protection
      clothing, and a single dose of 325 mg aspirin or placebo immediately following
      exertion. Peripheral arterial augmentation index adjusted for a heart rate of 75
      (AI75) and reactive hyperemia index (RHI) were determined immediately before, and
      30, 60, and 90 minutes after exertion. Low-dose aspirin was associated with lower
      AI75 (-15.25+/-9.25 vs -8.08+/-10.70, p=0.014) but not RHI. On repeated measures
      analysis, treatment with low-dose aspirin before, but not single-dose aspirin
      after exertion, was associated with lower AI75 following exertional heat stress
      (p=0.018). Low-dose aspirin improved peripheral arterial stiffness and wave
      reflection but not endothelial function in firefighters.

PMID- 25939658
TI  - Healthcare costs attributable to the treatment of patients with spinal
      metastases: a cohort study with up to 8 years follow-up.
AB  - BACKGROUND: Cancer treatment, and in particular end-of-life treatment, is
      associated with substantial healthcare costs. The purpose of this study was to
      analyse healthcare costs attributable to the treatment of patients with spinal
      metastases. METHODS: The study population (n = 629) was identified from clinical
      databases in Denmark. Patients undergoing spinal metastasis treatment from
      January 2005 through June 2012 were included. Clinical data were merged with
      national register data on healthcare resource use, costs and death date. The
      analytic period ranged from treatment initiation until death or administrative
      censoring in October 2013. Analysis of both survival and costs were stratified
      into four treatment regimens of increasing invasiveness: radiotherapy (T1),
      decompression (T2), decompression + instrumentation (T3) and decompression +
      instrumentation + reconstruction (T4). Survival was analysed using Kaplan-Meier
      curves. Costs were estimated from a healthcare perspective. Lifetime costs were
      defined as accumulated costs from treatment initiation until death. The Kaplan
      Meier Sampling Average method was used to estimate these costs; 95% CIs were
      estimated using nonparametric bootstrapping. RESULTS: Mean age of the study
      population was 65.2 years (range: 19-95). During a mean follow-up period of 9.2
      months (range: 0.1-94.5 months), post treatment survival ranged from 4.4 months
      (95% CI 2.5-7.5) in the T1 group to 8.7 months (95% CI 6.7-14.1) in the T4 group.
      Inpatient hospitalisation accounted for 65% and outpatient services for 31% of
      the healthcare costs followed by hospice placements 3% and primary care 1%.
      Lifetime healthcare costs accounted for ?36,616 (95% CI 33,835-39,583) per T1
      patients, ?49,632 (95% CI 42,287-57,767) per T2 patient, ?70997 (95% CI 62,244
      82,354) per T3 patient and ?87,814 (95% CI 76,638-101,528) per T4 patient.
      Overall, 45% of costs were utilised within the first month. T1 and T4 patients
      had almost identical distributions of costs: inpatient hospitalisation averaged
      59% and 36% for outpatient services. Costs of T2 and T3 were very similarly
      distributed with an average of 71% for inpatient hospitalisation and 25% for
      outpatient services. CONCLUSION: The index treatment accounts for almost half of
      lifetime health care costs from treatment initiation until death. As expected,
      lifetime healthcare costs are positively association with invasiveness of
      treatment.

PMID- 25939659
TI  - Estimating the Burden of Osteoarthritis to Plan for the Future.
AB  - OBJECTIVE: With aging and obesity trends, the incidence and prevalence of
      osteoarthritis (OA) is expected to rise in Canada, increasing the demand for
      health resources. Resource planning to meet this increasing need requires
      estimates of the anticipated number of OA patients. Using administrative data
      from Alberta, we estimated OA incidence and prevalence rates and examined their
      sensitivity to alternative case definitions. METHODS: We identified cases in a
      linked data set spanning 1993 to 2010 (population registry, Discharge Abstract
      Database, physician claims, Ambulatory Care Classification System, and
      prescription drug data) using diagnostic codes and drug identification numbers.
      In the base case, incident cases were captured for patients with an OA diagnostic
      code for at least 2 physician visits within 2 years or any hospital admission.
      Seven alternative case definitions were applied and compared. RESULTS: Age- and
      sex-standardized incidence and prevalence rates were estimated to be 8.6 and 80.3
      cases per 1,000 population, respectively, in the base case. Physician claims data
      alone captured 88% of OA cases. Prevalence rate estimates required 15 years of
      longitudinal data to plateau. Compared to the base case, estimates are sensitive
      to alternative case definitions. CONCLUSION: Administrative databases are a key
      source for estimating the burden and epidemiologic trends of chronic diseases
      such as OA in Canada. Despite their limitations, these data provide valuable
      information for estimating disease burden and planning health services. Estimates
      of OA are mostly defined through physician claims data and require a long period
      of longitudinal data.

PMID- 25939661
TI  - First Rank Symptoms for Schizophrenia (Cochrane Diagnostic Test Accuracy Review).

PMID- 25939660
TI  - Antivirus immune activity in multiple sclerosis correlates with MRI activity.
AB  - OBJECTIVE: The objective of this study was to determine whether reactivation of
      Epstein-Barr (EBV) or activation of the anti-EBV immune response correlates with
      MS disease activity on MR imaging. METHODS: Subjects with early, active relapsing
      remitting MS were studied for 16 weeks with blood and saliva samples collected
      every 2 weeks and brain MRI performed every 4 weeks. We isolated peripheral blood
      mononuclear cells from each blood sample and tested the immune response to EBV,
      autologous EBV-infected lymphoblastoid cell lines (LCL), human herpesvirus 6
      (HHV6), varicella zoster virus (VZV), tetanus, and mitogens. We measured the
      proliferative response and the number of interferon-gamma secreting cells with
      ELISPOT. We measured the amounts of EBV, HHV6, and VZV DNA in blood and saliva
      with quantitative PCR. On MRI, we measured number and volume of contrast
      enhancing and T2 lesions. We tested for correlation between the immunologic
      assays and the MRI results, assessing different time intervals between the MRI
      and immunologic assays. RESULTS: We studied 20 subjects. Ten had enhancing
      lesions on one or more MRI scans and one had new T2 lesions without enhancement.
      The most significant correlation was between proliferation to autologous LCL and
      the number of combined unique active lesions on MRI 4 weeks later. Both
      proliferation and number of cells secreting interferon-gamma in response to LCL
      correlated with the number of enhancing lesions 8 weeks later. CONCLUSIONS: We
      find evidence for correlation of antiviral immune responses in the blood with
      subsequent disease activity on MRI scans.

PMID- 25939662
TI  - Trends in U.S. life expectancy gradients: the role of changing educational
      composition.
AB  - BACKGROUND: I examined age patterns and the role of shifting educational
      distributions in driving trends in educational gradients in life expectancy among
      non-Hispanic Whites between 1991 and 2005. METHODS: Data were from the 1986-2004
      National Health Interview Survey with mortality follow-up through 2006. Life
      expectancies were computed by sex, period and education. Age decompositions of
      life expectancy gradients and composition-adjusted life expectancies were
      computed to account for age patterns and shifting educational distributions.
      RESULTS: Life expectancy at age 25 among White men increased for all education
      groups, decreased among the least-educated White women and increased among White
      women with college degrees. Much of the decline in measured life expectancy for
      White women with less than a high school education comes from the 85+ age group.
      Educational gradients in life expectancy widened for White men and women. One
      third of the gradient is due to ages below 50. Approximately 26% (0.7 years) and
      87% (0.8 years) of the widening of the gradient in life expectancy between ages
      25 and 85 for White women and men is attributable to shifting education
      distributions. Over half of the decline in temporary life expectancy among the
      least-educated White women is due to compositional change. CONCLUSIONS: Life
      expectancy has increased among White men for all education groups and has
      decreased among White women with less than a high school education, though not to
      the extent reported in previous studies. The fact that a large proportion of the
      change in education-specific life expectancy among women is due to the 85+ age
      group suggests changes in institutionalization may be affecting estimates. Much
      of the change in education-specific life expectancy and the growth in the
      educational gradient in life expectancy is due to the shifting distribution of
      individuals across education categories.

PMID- 25939663
TI  - Feeder-free and xeno-free culture of human pluripotent stem cells using UCBS
      matrix.
AB  - The ideal medium for human pluripotent stem cells (hPSCs) culture should be
      feeder-free, xeno-free, and completely defined. The present study aims to
      establish a new feeder-free and xeno-free system for culturing hPSCs. The system
      consists of the matrix, which was prepared from human umbilical cord blood serum
      (UCBS) and used to coat the culture plates, and the xeno-free medium, which was
      conventional serum-free hES medium supplemented with high concentrations of bFGF
      and Fibronectin. Compared with matrigel and mouse embryonic fibroblasts (MEFs),
      the UCBS matrix was proved to be equally suitable for the growth of hPSCs. After
      a series of experiments with different media and cytokins, the UCBS matrix was
      found worked the best with the basic medium (BM) supplemented with 20 ng/mL bFGF,
      10 ug/mL fibronectin and Y-27632 for culture of hES cells. The hPSCs maintained
      normal karyotype, high proliferation rate and self-renewal ability after
      continuous culture more than 10 passages in this feeder-free and xeno-free
      system. Furthermore, a new human embryonic stem (hES) cell line was derived from
      discarded day 3 embryos in this newly developed culture system. In conclusion,
      this feeder-free and xeno-free system could not only be used to the culture
      hPSCs, but could also be used to derive new hES cell lines.

PMID- 25939664
TI  - Juvenile myelomonocytic leukemia due to a germline CBL Y371C mutation: 35-year
      follow-up of a large family.
AB  - Juvenile myelomonocytic leukemia (JMML) is a pediatric myeloproliferative
      neoplasm that arises from malignant transformation of the stem cell compartment
      and results in increased production of myeloid cells. Somatic and germline
      variants in CBL (Casitas B-lineage lymphoma proto-oncogene) have been associated
      with JMML. We report an incompletely penetrant CBL Y371C mutation discovered by
      whole-exome sequencing in three individuals with JMML in a large pedigree with 35
      years of follow-up. The Y371 residue is highly evolutionarily conserved among CBL
      orthologs and paralogs. In silico bioinformatics prediction programs suggested
      that the Y371C mutation is highly deleterious. Protein structural modeling
      revealed that the Y371C mutation abrogated the ability of the CBL protein to
      adopt a conformation that is required for ubiquitination. Clinically, the three
      mutation-positive JMML individuals exhibited variable clinical courses; in two
      out of three, primary hematologic abnormalities persisted into adulthood with
      minimal clinical symptoms. The penetrance of the CBL Y371C mutation was 30% for
      JMML and 40% for all leukemia. Of the 8 mutation carriers in the family with
      available photographs, only one had significant dysmorphic features; we found no
      evidence of a clinical phenotype consistent with a "CBL syndrome". Although CBL
      Y371C has been previously reported in familial JMML, we are the first group to
      follow a complete pedigree harboring this mutation for an extended period,
      revealing additional information about this variant's penetrance, function and
      natural history.

PMID- 25939665
TI  - A cautionary note on the impact of protocol changes for genome-wide association
      SNP * SNP interaction studies: an example on ankylosing spondylitis.
AB  - Genome-wide association interaction (GWAI) studies have increased in popularity.
      Yet to date, no standard protocol exists. In practice, any GWAI workflow involves
      making choices about quality control strategy, SNP filtering, linkage
      disequilibrium (LD) pruning, analytic tool to model or to test for genetic
      interactions. Each of these can have an impact on the final epistasis findings
      and may affect their reproducibility in follow-up analyses. Choosing an analytic
      tool is not straightforward, as different tools exist and current understanding
      about their performance is based on often very particular simulation settings. In
      the present study, we wish to create awareness for the impact of (minor) changes
      in a GWAI analysis protocol can have on final epistasis findings. In particular,
      we investigate the influence of marker selection and marker prioritization
      strategies, LD pruning and the choice of epistasis detection analytics on study
      results, giving rise to 8 GWAI protocols. Discussions are made in the context of
      the ankylosing spondylitis (AS) data obtained via the Wellcome Trust Case Control
      Consortium (WTCCC2). As expected, the largest impact on AS epistasis findings is
      caused by the choice of marker selection criterion, followed by marker coding and
      LD pruning. In MB-MDR, co-dominant coding of main effects is more robust to the
      effects of LD pruning than additive coding. We were able to reproduce previously
      reported epistasis involvement of HLA-B and ERAP1 in AS pathology. In addition,
      our results suggest involvement of MAGI3 and PARK2, responsible for cell adhesion
      and cellular trafficking. Gene ontology biological function enrichment analysis
      across the 8 considered GWAI protocols also suggested that AS could be associated
      to the central nervous system malfunctions, specifically, in nerve impulse
      propagation and in neurotransmitters metabolic processes. 

PMID- 25939666
TI  - Feasibility of a rural palliative supportive service.
AB  - INTRODUCTION: Healthcare models for the delivery of palliative care to rural
      populations encounter common challenges: service gaps, the cost of the service in
      relation to the population, sustainability, and difficulty in demonstrating
      improvements in outcomes. Although it is widely agreed that a community capacity
      building approach to rural palliative care is essential, how that approach can be
      achieved, evaluated and sustained remains in question. The purpose of this
      community-based research project is to test the feasibility and identify
      potential outcomes of implementing a rural palliative supportive service (RPaSS)
      for older adults living with life-limiting chronic illness and their family
      caregiver in the community. This paper reports on the feasibility aspects of the
      study. METHODS: RPaSS is being conducted in two co-located rural communities with
      populations of approximately 10 000 and no specialized palliative services.
      Participants living with life-limiting chronic illness and their family
      caregivers are visited bi-weekly in the home by a nurse coordinator who
      facilitates symptom management, teaching, referrals, psychosocial and spiritual
      support, advance care planning, community support for practical tasks, and
      telephone-based support for individuals who must commute outside of the rural
      community for care. Mixed-method collection strategies are used to collect data
      on visit patterns; healthcare utilization; family caregiver needs; and
      participant needs, functional performance and quality of life. RESULTS: A
      community-based advisory committee worked with the investigative team over a 1
      year period to plan RPaSS, negotiating the best fit between research methods and
      the needs of the community. Recruitment took longer than anticipated with service
      capacity being reached at 8 months. Estimated service capacity of one nurse
      coordinator, based on bi-weekly visits, is 25 participants and their family
      caregivers. A total of 393 in-person visits and 53 telephone visits were
      conducted between January 2013 and May 2014. Scheduled in-person visit duration
      showed a mean of 67 minutes. During this same time period only 19 scheduled
      visits were declined, and there was no study attrition except through death,
      indicating a high degree of acceptability of the intervention. The primary needs
      that were addressed during these visits have been related to chronic disease
      management, and the attending physical symptoms were addressed through teaching
      and support. The use of structured quality of life and family caregiver needs
      assessments has been useful in facilitating communication, although some
      participants experienced the nature of the questions as too personal in the early
      stages of the relationship with the nurse coordinator. CONCLUSIONS: Findings from
      this study illustrate the feasibility of providing home-based services for rural
      older adults living with life-limiting chronic illness. The RPaSS model has the
      potential to smooth transitions and enhance quality of life along the disease
      trajectory and across locations of care by providing a consistent source of
      support and education. This type of continuity has the potential to foster the
      patient- and family-centered approach to care that is the ideal of a palliative
      approach. Further, the use of a rural community capacity-building approach may
      contribute to sustainability, which is a particularly important part of rural
      health service delivery.

PMID- 25939667
TI  - Mechanisms, injuries and helmet use in cyclists presenting to an inner city
      emergency department.
AB  - OBJECTIVES: The objectives of the present study were to describe the injury
      profiles of cyclists presenting to an ED and determine the risk of significant
      head injury associated with bicycle helmet use. METHODS: This was a retrospective
      single trauma centre study of all adult cyclists presenting to an inner city ED
      and undergoing a trauma team review between January 2012 and June 2014. The
      outcome of interest was significant head injury defined as any head injury with
      an Abbreviated Injury Scale score of two or more. Variables analysed included
      demographic characteristics, helmet use at time of incident, location, time and
      the presence of intoxication. RESULTS: The most common body regions were upper
      limb injuries (57%), followed by head injuries (43%), facial injuries (30%) and
      lower limb injuries (24%). A lower proportion of people wearing helmets had
      significant head injury (17% vs 31%, P = 0.018) or facial injury (26% vs 48%, P =
      0.0017) compared with non-helmet users. After adjustment for important
      covariates, helmet use was associated with a 70% decrease in the odds of
      significant head injury (odds ratio 0.34, 95% confidence interval 0.15, 0.76, P =
      0.008). CONCLUSIONS: Head injuries were common after inner city cycling
      incidents. The use of helmets was associated with a reduction in significant head
      injury.

PMID- 25939668
TI  - Bright CuInS2/CdS nanocrystal phosphors for high-gain full-spectrum luminescent
      solar concentrators.
AB  - The performance of colloidal CuInS2/CdS nanocrystals as phosphors for full
      spectrum luminescent solar concentrators has been examined. Their combination of
      large solar absorption, high photoluminescence quantum yields, and only moderate
      reabsorption produces the highest projected flux gains of any nanocrystal
      luminophore to date. 

PMID- 25939669
TI  - Flexibility in metabolic rate confers a growth advantage under changing food
      availability.
AB  - 1. Phenotypic flexibility in physiological, morphological and behavioural traits
      can allow organisms to cope with environmental challenges. Given recent climate
      change and the degree of habitat modification currently experienced by many
      organisms, it is therefore critical to quantify the degree of phenotypic
      variation present within populations, individual capacities to change and what
      their consequences are for fitness. 2. Flexibility in standard metabolic rate
      (SMR) may be particularly important since SMR reflects the minimal energetic cost
      of living and is one of the primary traits underlying organismal performance. SMR
      can increase or decrease in response to food availability, but the consequences
      of these changes for growth rates and other fitness components are not well
      known. 3. We examined individual variation in metabolic flexibility in response
      to changing food levels and its consequences for somatic growth in juvenile brown
      trout (Salmo trutta). 4. SMR increased when individuals were switched to a high
      food ration and decreased when they were switched to a low food regime. These
      shifts in SMR, in turn, were linked with individual differences in somatic
      growth; those individuals that increased their SMR more in response to elevated
      food levels grew fastest, while growth at the low food level was fastest in those
      individuals that depressed their SMR most. 5. Flexibility in energy metabolism is
      therefore a key mechanism to maximize growth rates under the challenges imposed
      by variability in food availability and is likely to be an important determinant
      of species' resilience in the face of global change.

PMID- 25939670
TI  - Probing cell-surface carbohydrate binding proteins with dual-modal glycan
      conjugated nanoparticles.
AB  - Dual-modal fluorescent magnetic glyconanoparticles have been prepared and shown
      to be powerful in probing lectins displayed on pathogenic and mammalian cell
      surfaces. Blood group H1- and Le(b)-conjugated nanoparticles were found to bind
      to BabA displaying Helicobacter pylori, and Le(a)- and Le(b)-modified
      nanoparticles are both recognized by and internalized into DC-SIGN and SIGN-R1
      expressing mammalian cells via lectin-mediated endocytosis. In addition,
      glyconanoparticles block adhesion of H. pylori to mammalian cells, suggesting
      that they can serve as inhibitors of infection of host cells by this pathogen. It
      has been also shown that owing to their magnetic properties, glyconanoparticles
      are useful tools to enrich lectin expressing cells. The combined results indicate
      that dual-modal glyconanoparticles are biocompatible and that they can be
      employed in lectin-associated biological studies and biomedical applications. 

PMID- 25939671
TI  - Spinal cord injury--incidence, prognosis, and outcome: an analysis of the
      TraumaRegister DGU.
AB  - BACKGROUND CONTEXT: Little is known about the incidence of spinal cord injury
      (SCI) in polytrauma patients. PURPOSE: The purpose of this study was to analyze
      incidence, prognosis, and outcome of SCI in polytrauma patients. STUDY
      DESIGN/SETTING: This is a retrospective multicenter cohort study. PATIENT SAMPLE:
      A total of 57,310 patients of TraumaRegister DGU (2002-2012) of the German Trauma
      Society were included. Aim of this large multicentre database is a standardized
      documentation of severely injured patients. OUTCOME MEASURES: Outcome measures
      were mortality and Glasgow Outcome 4Scale. METHODS: Inclusion criteria were adult
      blunt trauma patients (age greater than 16 years) and injury severity score (ISS)
      greater than 16. The severity of SCI was based on the Abbreviated Injury Scale
      (AIS), and the outcome of patients was assessed with the Glasgow Outcome Scale
      (GOS). Factors with an impact on the outcome were analyzed with a logistic
      regression model. RESULTS: Four thousand two hundred eighty five (7.5%) of 57,310
      patients sustained SCI. Mean age was 48.9+/-20.7 years, ISS 28.0+/-12, and 72.7%
      were men. Two thousand two hundred twenty two (3.9%) SCIs involved the cervical,
      1,388 (2.4%) the thoracic, and 791 (1.4%) the lumbar spine. One hundred fifty
      nine (7.2%) cervical spine injuries were associated with transient neurologic
      deficit (TND) (AIS 3), 612 (27.5%) with an incomplete paraplegia (AIS 4), 1,101
      (49.6%) with a complete paraplegia (AIS 5), and 350 (15.8%) with a complete
      lesion above C3 (AIS 6). Lesions of the thoracic spine showed in 93 (6.7%) of the
      1,388 lesions a TND (AIS 3), in 332 (23.9%) an incomplete paraplegia (AIS 4), and
      in 963 (69.4%) a complete lesion (AIS 5). In the lumbar region, lesions were
      distributed as follows: TND (AIS 3) 145 (18.3%), incomplete paraplegia (AIS 4)
      305 (38.6%), and complete lesion 341 (43.1%). Sepsis and multiorgan failure were
      found more often in patients with AIS 5/6 lesions (p<.001). The hospital length
      of stay in SCIs was significantly longer. Most of the patients (85.8%) with SCI
      were treated in Level I trauma centers. Spinal cord injuries had a minor impact
      in the mortality. Only AIS 6 injuries resulted in a significantly higher
      mortality (64.6%). Adjusted logistic regression analysis (target variable: GOS 4
      or 5, good outcome) showed that the following factors were significantly
      associated with an unfavorable outcome (p<=.02): AIS greater than or equal to 4,
      age greater than or equal to 60 years, resuscitation, severe head injury, shock
      on scene, and severity of injury (ISS per point). CONCLUSIONS: Spinal cord injury
      with a neurologic deficit could be found in every 13th patient with polytrauma.
      Over half of the patients with SCI suffer from complete cord lesion. In
      polytrauma patients, SCI only has a limited influence on the mortality, with
      exception of AIS 6 lesions. Complications such as multiorgan failure or sepsis
      and extended hospital length of stay are more frequent in SCI.

PMID- 25939672
TI  - The radiologic, clinical results and digestive function improvement in patients
      with ankylosing spondylitis kyphosis after pedicle subtraction osteotomy.
AB  - BACKGROUND CONTEXT: Although there have been several reports describing the
      radiologic and clinical outcomes of pedicle subtraction osteotomy (PSO) in
      ankylosing spondylitis (AS) with spinal kyphotic deformity, little is known about
      the digestive function improvement in AS kyphosis after PSO. PURPOSE: The aim was
      to assess radiologic and clinical results and digestive function improvement in
      patients with AS kyphosis after PSO. STUDY DESIGN/SETTING: This was a
      retrospective clinical study. PATIENT SAMPLE: From January 2009 to July 2013, 53
      patients in our department with AS kyphotic deformity who underwent PSO were
      reviewed. OUTCOME MEASURES: The globe kyphosis (GK) was measured. A health
      related quality of life included Oswestry Disability Index (ODI) and Scoliosis
      Research Society outcomes instrument-22 (SRS-22). The acreage of the abdominal
      median sagittal plane (AMSPA) and the minimum distance (MD) between the xiphoid
      process and the spine or between the abdominal wall and the spine when the
      abdominal wall was folded into abdomen were measured on the three-dimensional
      computed tomography scans. The positional changes of abdominal viscera, such as
      the liver, spleen, and kidney, were also measured. Digestive function assessment
      included weight and the food intake (FI), and the change of the defecate
      frequency was recorded. METHODS: A paired sample t test was performed to
      determine the differences between the preoperative and postoperative MD, AMSPA,
      and weight, respectively. A paired sample t test was also performed to determine
      the differences between preoperative and postoperative Cobb angles and Oswestry
      Disability Index (ODI), SRS-22 for all the patients, respectively. A paired
      sample t test was also performed to determine the positional changes of abdominal
      viscera. Description date was presented as mean+/-standard deviation.
      Additionally, an independent sample t test was performed to determine the
      differences between the patients (Group 1) who had defecate frequency change and
      the remaining patients (Group 2) for preoperative GK, age, and disease duration,
      respectively. An independent sample t test was also performed to determine the
      differences between the patients (Group A) who had obviously increased FI and the
      remaining patients (Group B) for preoperative GK, age, and disease duration,
      respectively. RESULTS: All the patients had good radiologic and clinical results,
      postoperatively. The postoperative positions of the abdominal viscera were
      changed significantly. The weight, the mass of FI, and the defecate frequency
      were also changed significantly, postoperatively. The preoperative GK, age, and
      disease duration were not significantly statistical different between the
      patients who had defecate frequency change and the remaining patients,
      respectively. There were also not significantly statistical differences between
      the patients who had obviously increased FI and the remaining patients in
      preoperative age and disease duration. There was a significantly statistical
      difference between the patients who had obviously increased FI and the remaining
      patients for preoperative GK. CONCLUSIONS: The single-level or two-level PSO is
      an effective and safe technique to correct AS kyphosis. And the conditions of
      extrusion of viscera by trunk flexion decreased volume of the abdominal cavity,
      and abnormal visceral positions were improved by the osteotomy, followed with
      digestive function improvement.

PMID- 25939673
TI  - Statin-associated ocular disorders: the FDA and ADRAC data.
AB  - BACKGROUND: Statins are a class of medication indicated for atherosclerotic
      diseases and dyslipidemia. Since their appearance, many adverse events have been
      associated with their use. Ocular disorders are rare but serious adverse events
      of statins. OBJECTIVE: To report the association between statins and ocular
      adverse events (blurred vision, visual impairment, visual field defect, reduced
      visual acuity, myopia, hypermetropia, presbyopia, and astigmatism) which might be
      associated with muscle or liver problems by examining the frequency of ocular
      adverse events among the reported adverse drug reactions from the Food and Drug
      Administration (FDA) and Adverse Drug Reactions Advisory Committee (ADRAC) data.
      Setting The FDA USA and ADRAC Australia databases. METHODS: We conducted a
      retrospective study of statin-associated ocular adverse events reported to FDA
      between 1988 and 2013 and ADRAC between 1988 and 2011. The recoded data included:
      patient's age, gender, suspected drug and dosage, concomitant drug, adverse
      events, duration of therapy, dechallenge and rechallenge therapy. The differences
      in the adverse events profiles between each of the statins and atorvastatin were
      performed using Chi square and multivariate (logistic regression) statistical
      tests. MAIN OUTCOME MEASURE: Percentages of subjects correlated with each Ocular
      adverse events. RESULTS: Among 131,755 cases of patients taking statins in the
      FDA, there were 2325 cases reported ocular adverse events after using statins
      (1.8%). The Chi square statistic showed that the proportions of ocular adverse
      events varied significantly (p < 0.0001) across the different statin drugs. The
      most highly reported ocular adverse events associated with statins were blurred
      vision (48.4%) and visual impairment (25.7%). Results from logistic regression
      indicated that the ocular problems formed a greater proportion of the adverse
      events for subjects taking atorvastatin (2.1%). Of the 1.8%, ocular adverse
      events mostly occurred alone (60.9%), followed by 30.3% where muscle adverse
      events also were involved. The ADRAC data held 136 cases of statins associated
      ocular adverse events (47 patients reported blurred vision and 64 reported vision
      impairment). CONCLUSION: All statins were associated with ocular side effects,
      with atorvastatin showed a higher incidence of ocular side effects in conjunction
      with muscle and liver problems.

PMID- 25939674
TI  - PAD in women: the ischemic continuum.
AB  - Lower extremity peripheral arterial disease (PAD) is part of the ischemic
      continuum of atherosclerotic vascular disease and is associated with an increased
      risk of myocardial infarction, stroke, and cardiovascular death. Compared to men,
      women with PAD are more likely to have asymptomatic disease or atypical symptoms.
      PAD in women is associated with decreased exercise capacity, reduced quality of
      life, increased risk of depression, as well as a greater risk of acute
      cardiovascular events and cardiovascular mortality than male counterparts.
      Ensuring an appropriate diagnosis of women with PAD offers an opportunity to
      begin risk factor modification therapy, improve walking capacity and make a
      timely referral for revascularization if needed. It is critical to highlight the
      sex-based disparities in lower extremity PAD so that we may work to improve
      outcomes for women with PAD. 

PMID- 25939675
TI  - Desperately seeking parenthood: neonatal nurses reflect on parental anguish.
AB  - AIM AND OBJECTIVE: This paper aims to explore the ways in which neonatal nurses
      understand the experience of parents who have experienced infertility, conceived
      a baby via in vitro fertilisation and delivered an extremely premature infant.
      The chance of a poor long-term outcome for the baby is significant; therefore,
      parental anguish plays out in the neonatal intensive care. BACKGROUND: Current
      literature suggests that infertility is a significant issue for ageing women and
      many couples experience multiple cycles of invitro-fertilisation (IVF) treatment
      to achieve a pregnancy. Babies conceived through IVF are more likely to have
      genetic disorders, and be born prematurely. When the baby is born through IVF and
      is also born extremely prematurely, it creates a crisis situation for the
      parents. This paper will focus on the parental anguish of achieving a pregnancy
      through IVF to see the baby born extremely prematurely (defined as <= 24-week
      gestation). It will examine parental anguish from caregiver perspective of the
      neonatal nurse who supports the parents through this very difficult time. DESIGN:
      This study used interviews with neonatal nurses, and drew insights from
      interpretative phenomenology. METHODS: This research used a combination of a
      questionnaire and a series of interviews in a qualitative study informed by
      phenomenology. The analysis of the interview data involved the creation of key
      themes following extensive coding of thematic statements and the analysis of the
      emerging themes. RESULTS: This paper outlines the neonatal nurses' understanding
      of parental anguish and overwhelming sadness in parents whose baby was conceived
      by IVF, and was also born extremely prematurely. The theme of 'seeking
      parenthood' was synthesised from two sub-themes - 'longing for a baby' and 'the
      desperation to become parents'. CONCLUSION: This study identified that neonatal
      nurses bear witness to parental anguish as their hopes of taking home a live baby
      might not be realised. The time, effort and money required to achieve a pregnancy
      does not mean that the baby will be spared the outcomes of extreme prematurity
      and the risk factors associated with IVF. The parents may be left empty handed.
      Therefore, the word precious becomes a metaphor for the IVF baby as the neonatal
      team try desperately to give the parents their much longed baby. RELEVANCE TO
      CLINICAL PRACTICE: Delayed child bearing has an impact on fertility, with
      maternal age having the most impact on the ability to conceive. Babies conceived
      through IVF technologies have a higher risk of genetic abnormalities and being
      born prematurely, and this will impact on the neonatal intensive care
      availability. Extreme prematurity and IVF can significantly impact on the baby's
      outcome. Witnessing parental anguish can be a major source of stress for the
      neonatal nurses. Neonatal nurses need to develop strategies not only to help the
      parents but also to prevent the parents' overwhelming sadness from affecting
      their ability to function in the neonatal intensive care unit.

PMID- 25939676
TI  - Individual and occupational characteristics associated with respiratory symptoms
      among Latino horse farm workers.
AB  - BACKGROUND: Latino workers are likely exposed to a variety of respiratory hazards
      in the horse barn, yet the potential impact of these exposures on respiratory
      health has not been investigated. METHODS: Using a community-based sample of 225
      Latino horse farmworkers we investigated the prevalence of upper and lower
      respiratory symptoms and occupational characteristics associated with them.
      Multivariable logistic regression was used to identify factors associated with
      respiratory symptomology. RESULTS: Upper respiratory symptoms prevalence ranged
      from 24% to 45%. Half of workers reported lower respiratory symptoms. Workers
      with symptoms were more likely to be female and have lower levels of English
      understanding. Workers who never/rarely used dust masks while working in the barn
      experienced over two times the odds of reporting upper respiratory symptoms.
      CONCLUSIONS: Many Latino horse workers experienced upper and lower respiratory
      symptoms. Dust mask use may protect workers in this and other enclosed livestock
      operations from respiratory symptoms.

PMID- 25939677
TI  - First efficient CRISPR-Cas9-mediated genome editing in Leishmania parasites.
AB  - Protozoan pathogens that cause leishmaniasis in humans are relatively refractory
      to genetic manipulation. In this work, we implemented the CRISPR-Cas9 system in
      Leishmania parasites and demonstrated its efficient use for genome editing. The
      Cas9 endonuclease was expressed under the control of the Dihydrofolate Reductase
      Thymidylate Synthase (DHFR-TS) promoter and the single guide RNA was produced
      under the control of the U6snRNA promoter and terminator. As a proof of concept,
      we chose to knockout a tandemly repeated gene family, the paraflagellar rod-2
      locus. We were able to obtain null mutants in a single round of transfection. In
      addition, we confirmed the absence of off-target editions by whole genome
      sequencing of two independent clones. Our work demonstrates that CRISPR-Cas9
      mediated gene knockout represents a major improvement in comparison with existing
      methods. Beyond gene knockout, this genome editing tool opens avenues for a
      multitude of functional studies to speed up research on leishmaniasis. 

PMID- 25939678
TI  - Pharmacometrics-guided drug development of antihyperhidrosis agents.
AB  - The objective of the present work was to use modeling and simulation to inform
      trial design of a proof-of-concept study for agents used in the treatment of
      hyperhidrosis. Data were available from 36 subjects who received the vehicle, 2%
      or 4% topical glycopyrrolate wipes daily for 4 weeks, with response
      (hyperhidrosis disease severity scale [HDSS] and sweat production [SP]) measured
      weekly. The HDSS and SP time courses were best described using a longitudinal
      model with maximum response achieved by 1 week. Glycopyrrolate 4% had a higher
      HDSS responder rate than 2% (50% vs 33%) and placebo (0%) at week 1. Mean change
      from baseline (mg/5 min [SD]) in SP at week 1 was -90 (220), -185 (214), and -271
      (265) for placebo, 2%, and 4% glycopyrrolate, respectively. Subjects with higher
      baseline SP had higher sweat reduction from baseline. Virtual clinical trials
      were simulated and analyzed using conventional (at the end of the study) versus
      model-based methods to determine sample size for achieving 80% power to identify
      a dose-response relationship. Twenty-seven subjects compared with at least 120
      subjects would be needed using model-based and conventional methods,
      respectively. Thus, the model-based method using longitudinal data required fewer
      subjects than the conventional single-point method. 

PMID- 25939679
TI  - A review of the methods for neuronal response latency estimation.
AB  - Neuronal response latency is usually vaguely defined as the delay between the
      stimulus onset and the beginning of the response. It contains important
      information for the understanding of the temporal code. For this reason, the
      detection of the response latency has been extensively studied in the last twenty
      years, yielding different estimation methods. They can be divided into two
      classes, one of them including methods based on detecting an intensity change in
      the firing rate profile after the stimulus onset and the other containing methods
      based on detection of spikes evoked by the stimulation using interspike intervals
      and spike times. The aim of this paper is to present a review of the main
      techniques proposed in both classes, highlighting their advantages and
      shortcomings. 

PMID- 25939680
TI  - Electrically pumped random lasing with an onset voltage of sub-3 V from ZnO-based
      light-emitting devices featuring nanometer-thick MoO3 interlayers.
AB  - We have previously reported on electrically pumped random lasing (RL) with onset
      voltages at least 3.3 V from ZnO-based light-emitting devices with metal
      insulator-semiconductor (MIS) structures in the form of Au/SiO2/ZnO. Here, by
      inserting an ~5 nm thick MoO3 layer between SiO2 and ZnO films in the
      aforementioned MIS structured device, the RL onset voltage is decreased to only
      ~2.6 V and, moreover, the output optical power is multiplied several times. Such
      improved RL performance is ascribed to the enhanced injection of holes into ZnO
      via the MoO3 interlayer that features a low-lying conductive band and therefore a
      large work function. 

PMID- 25939681
TI  - Class and comparison: subjective social location and lay experiences of
      constraint and mobility.
AB  - Lay perceptions and experiences of social location have been commonly framed with
      reference to social class. However, complex responses to, and ambivalence over,
      class categories have raised interesting analytic questions relating to how
      sociological concepts are operationalized in empirical research. For example,
      prior researchers have argued that processes of class dis-identification signify
      moral unease with the nature of classed inequalities, yet dis-identification may
      also in part reflect a poor fit between 'social class' as a category and the ways
      in which people accord meaning to, and evaluate, their related experiences of
      socio-economic inequality. Differently framed questions about social comparison,
      aligned more closely with people's own terms of reference, offer an interesting
      alternative avenue for exploring subjective experiences of inequality. This paper
      explores some of these questions through an analysis of new empirical data,
      generated in the context of recession. In the analysis reported here, class
      identification was common. Nevertheless, whether or not people self identified in
      class terms, class relevant issues were perceived and described in highly diverse
      ways, and lay views on class revealed it to be a very aggregated as well as
      multifaceted construct. It is argued that it enables a particular, not general,
      perspective on social comparison. The paper therefore goes on to examine how
      study participants compared themselves with familiar others, identified by
      themselves. The evidence illuminates social positioning in terms of constraint,
      agency and (for some) movement, and offers insight into very diverse experiences
      of inequality, through the comparisons that people made. Their comparisons are
      situated, and pragmatic, accounts of the material contexts in which people live
      their lives. Linked evaluations are circumscribed and strongly tied to these
      proximate material contexts.The paper draws out implications for theorizing lay
      perspectives on class, and subjective experiences of inequality. 

PMID- 25939682
TI  - Improving postoperative pain control in paediatric tonsillectomy through use of a
      specialist information leaflet: Our experience in 43 patients.

PMID- 25939683
TI  - Enzyme-resistant isomalto-oligosaccharides produced from Leuconostoc
      mesenteroides NRRL B-1426 dextran hydrolysis for functional food application.
AB  - The extracellular dextransucrase from Leuconostoc mesenteroides NRRL B-1426 was
      produced and purified using polyethylene glycol fractionation. In our earlier
      study, it was reported that L. mesenteroides dextransucrase synthesizes a high
      molecular mass dextran (>2 * 10(6)  Da) with ~85.5% alpha-(1->6) linear and
      ~14.5% alpha-(1->3) branched linkages. Isomalto-oligosaccharides (IMOs) were
      synthesized through depolymerization of dextran by the action of dextranase. The
      degree of polymerization of IMOs was 2-10 as confirmed by mass spectrometry. The
      nuclear magnetic resonance spectroscopic analysis revealed the presence of alpha
      (1->3) linkages in the synthesized IMOs. The IMOs were resistant to dextranase,
      alpha-glucosidase, and alpha-amylase, and therefore can have potential
      application as food additives in the functional foods. 

PMID- 25939684
TI  - Efficacy of laparoscopic subtotal gastrectomy with D2 lymphadenectomy for locally
      advanced gastric cancer: the protocol of the KLASS-02 multicenter randomized
      controlled clinical trial.
AB  - BACKGROUND: Despite the well-described benefits of laparoscopic surgery such as
      lower operative blood loss and enhanced postoperative recovery in gastric cancer
      surgery, the application of laparoscopic surgery in patients with locally
      advanced gastric cancer (AGC) remains elusive owing to a lack of clinical
      evidence. Recently, the Korean Laparoscopic Surgical Society Group launched a new
      multicenter randomized clinical trial (RCT) to compare laparoscopic and open D2
      lymphadenectomy for patients with locally AGC. Here, we introduce the protocol of
      this clinical trial. METHODS/DESIGN: This trial is an investigator-initiated,
      randomized, controlled, parallel group, non-inferiority trial. Gastric cancer
      patients diagnosed with primary tumors that have invaded into the muscle propria
      and not into an adjacent organ (cT2-cT4a) in preoperative studies are recruited.
      Another criterion for recruitment is no lymph node metastasis or limited
      perigastric lymph node (including lymph nodes around the left gastric artery)
      metastasis. A total 1,050 patients in both groups are required to statistically
      show non-inferiority of the laparoscopic approach with respect to the primary end
      point, relapse-free survival of 3 years. Secondary outcomes include postoperative
      morbidity and mortality, postoperative recovery, quality of life, and overall
      survival. Surgeons who are validated through peer-review of their surgery videos
      can participate in this clinical trial. DISCUSSION: This clinical trial was
      designed to maintain the principles of a surgical clinical trial with internal
      validity for participating surgeons. Through the KLASS-02 RCT, we hope to show
      the efficacy of laparoscopic D2 lymphadenectomy in AGC patients compared with the
      open procedure. TRIAL REGISTRATION: ClinicalTrial.gov, NCT01456598.

PMID- 25939685
TI  - Association between three different cognitive behavioral alcohol treatment
      programs and recidivism rates among male offenders: findings from the United
      Kingdom.
AB  - BACKGROUND: Cognitive behavioral therapy-based alcohol treatment programs have
      been widely used to break the link between alcohol and crime. While evidence
      exists on the connection between alcohol and crime, there is little data that
      demonstrate the effectiveness of different alcohol treatment programs in reducing
      criminal behavior. We tested whether male offenders who participate in alcohol
      treatment programs show lower rates of recidivism than a matched offender group
      who did not participate in an alcohol prevention program. METHODS: This is an
      observational matched case-control study. Participants were 564 male offenders
      with an alcohol problem related to offending. Participants were assigned by the
      courts to 1 of 3 alcohol treatment programs (141 offenders per treatment): Low
      Intensity Alcohol Program (LIAP), Alcohol Specified Activity Requirement, and
      Addressing Substance-Related Offending. A fourth matched group (n = 141) was not
      assigned to a program and served as a control group. Survival analysis was used
      to calculate participants' charged and reconviction rates over 4 time periods (0
      to 3, 4 to 6, 7 to 9, and 10 to 12 months after completion of program or order).
      RESULTS: Offenders who did not participate in a program were more than twice as
      likely to be charged compared to offenders who participated in a program.
      Furthermore, offenders who did not participate in a program were over 2.5 times
      more likely to be reconvicted. Among the 3 alcohol treatment programs evaluated,
      the LIAP was the most cost-effective. CONCLUSIONS: Offenders enrolled in an
      alcohol treatment program showed a significant reduction in being charged with or
      reconvicted of a crime. With costs of keeping offenders in prison per year
      reaching close to L40,000 per offender per year (Mulheirn et al., 2010,
      www.smf.co.uk), assigning offenders to alcohol preventive programs-such as LIAP
      are a promising way to reduce recidivism and reduce cost.

PMID- 25939686
TI  - The relationships of coping, negative thinking, life satisfaction, social
      support, and selected demographics with anxiety of young adult college students.
AB  - PROBLEM: Understanding young adults' anxiety requires applying a multidimensional
      approach to assess the psychosocial, behavioral, and cognitive aspects of this
      phenomenon. METHODS: A hypothesized model of the relationships among coping
      style, thinking style, life satisfaction, social support, and selected
      demographics and anxiety among college students was tested using path analysis. A
      total of 257 undergraduate students aged 18-24 years completed an online survey.
      The independent variables were measured using the Multidimensional Scale of
      Perceived Social Support, the Brief Students' Multidimensional Life Satisfaction
      Scale, the Brief COPE Inventory, the Positive Automatic Thoughts Questionnaire,
      and the Cognition Checklist-Anxiety. The outcome, anxiety, was measured using the
      Anxiety subscale of the 21-item Depression Anxiety and Stress Scale. FINDINGS:
      Only negative thinking and maladaptive coping had a direct relationship with
      anxiety. Negative thinking was the strongest predictor of both maladaptive coping
      and anxiety. CONCLUSION: These findings suggest that helping undergraduates
      manage their anxiety by reducing their negative thinking is critical. Designing
      and testing interventions to decrease negative thinking in college students is
      recommended for future research.

PMID- 25939687
TI  - A case of esophageal adenocarcinoma on long-term rapamycin monotherapy.
AB  - Cancer in transplant recipients represents a therapeutic challenge even when the
      patient is already under mTOR inhibitors. A 78-year-old man received a deceased
      donor kidney transplant in 1993. After 6 months, he developed a multifocal
      cutaneous and nonvisceral Kaposi's Sarcoma while on cyclosporine
      immunosuppressant therapy. The patient was converted to sirolimus monotherapy in
      2001 with subsequent complete recovery within 2 years. In 2007, the patient was
      diagnosed with an esophageal adenocarcinoma stage IIA. An esophagectomy was
      performed without requirement of further treatment. He has continued on sirolimus
      monotherapy ever since, with no other incidents and no recurrences of either
      tumor. In this report, we describe an interesting case of a second cancer while
      on immunosuppressive therapy with anticancer activity. Moreover, the present
      knowledge of the matter is discussed.

PMID- 25939688
TI  - Willingness to complete advance directives among low-income older adults living
      in the USA.
AB  - This study explored low-income older adults' willingness to (i) complete advance
      directives, legal documents, whereby an individual designates decision-makers in
      the event that they cannot make their own decisions about end-of-life treatment
      preferences, and (ii) the role of social support and other predictors that impact
      their willingness. This study was conducted as part of a larger study exploring
      behaviours of advance care planning among low-income older adults. Out of a total
      of 255 participants from the original study, this study included 204 participants
      who did not complete an advance directive for data analysis. A cross-sectional
      study using probability random sampling stratified by ethnicity was used. Older
      adults residing in two supportive housing facilities or who were members of a
      senior centre in San Diego, California, USA, were interviewed in person between
      December 2010 and April 2011. Hierarchical logistic regression analysis revealed
      that the majority of participants (72.1%) were willing to complete advance
      directives and the factors significantly predicting willingness to complete
      included self-rated health, attitudes towards advance decision-making and social
      support. Participants with a poorer health status (OR = 1.43, 95% CI = 1.07-1.90)
      were more willing to complete advance directives. Conversely, participants with
      higher positive attitudes (OR = 1.18, 95% CI = 1.00-1.39) and greater social
      support (OR = 1.07, 95% CI = 1.00-1.15) were also more willing to complete
      advance directives. The findings suggest the importance of ongoing support from
      healthcare professionals in end-of-life care planning. Healthcare professionals
      can be a source of support assisting older adults in planning end-of-life care.
      Initiating ongoing communication regarding personal value and preference for end
      of-life care, providing relevant information and evaluating willingness to
      complete as well as assisting in the actual completion of advance directives will
      be necessary.

PMID- 25939689
TI  - A molecular dynamics study of CaCO3 nanoparticles in a hydrophobic solvent with a
      stearate co-surfactant.
AB  - Stearates containing overbased detergent nanoparticles (NPs) are used as acid
      neutralising additives in automotive and marine engine oils. Molecular dynamics
      (MD) simulations of the self-assembly of calcium carbonate, calcium stearate as a
      co-surfactant and stabilising surfactants of such NPs in a model explicit
      molecular hydrophobic solvent have been carried out using a methodology described
      first by Bodnarchuk et al. [J. Phys. Chem. C, 2014, 118, 21092]. The cores and
      particles as a whole become more elongated with stearate, and the surfactant
      molecules are more spaced out in this geometry than in their stearate-free
      counterparts. The rod dimensions are found to be largely independent of the
      surfactant type for a given amount of CaCO3. The corresponding particles without
      stearate were more spherical, the precise shape depending to a greater extent on
      the chemical architecture of the surfactant molecule. The rod-shaped stearate
      containing nanoparticles penetrated a model water droplet to a greater depth than
      the corresponding near-spherical particle, which is possibly facilitated by the
      dissociation of nanoparticle surfactant molecules onto the surface of the water
      in this process. These simulations are the first to corroborate the nanoparticle
      water penetration mechanism proposed previously by experimental groups
      investigating the NP acid neutralisation characteristics. 

PMID- 25939690
TI  - Tracking multiple modes of endocrine activity in Australia's largest inland
      sewage treatment plant and effluent- receiving environment using a panel of in
      vitro bioassays.
AB  - Estrogenicity of sewage effluents, and related ecotoxicological effects in
      effluent-receiving environments, have been widely reported over the last 2
      decades. However, relatively little attention has been given to other endocrine
      pathways that may be similarly disrupted by a growing list of contaminants of
      concern. Furthermore, the Australian evidence base is limited compared with those
      of Europe and North America. During a low dilution period in summer, the authors
      investigated multiple endocrine potencies in Australia's largest inland sewage
      treatment plant (STP) and the Lower Molonglo/Upper Murrumbidgee effluent
      receiving environment. This STP receives 900 L/s of mostly domestic wastewater
      from a population of 350 000, and contributes a high proportion of total flow in
      the lower catchment during dry periods. A panel of in vitro receptor-driven
      transactivation assays were used to detect (anti)estrogenic, (anti) androgenic,
      (anti)progestagenic, glucocorticoid, and peroxisome-proliferator activity at
      various stages of the sewage treatment process. Total estrogenic and
      (anti)androgenic potency was removed after primary and/or secondary treatment;
      however, total removal efficiency for glucocorticoid potency was poorer (53-66%),
      and progestagenic potency was found to increase along the treatment train.
      Estrogenicity was detected in surface waters and bed sediments upstream and
      downstream of the effluent outfall, at maximum levels 10 times lower than low
      hazard thresholds. Glucocorticoid and progestagenic activity were found to
      persist to 4 km downstream of the effluent outfall, suggesting that future
      research is needed on these endocrine-disrupting chemical categories in effluent
      receiving systems.

PMID- 25939691
TI  - Patch test results in children and adolescents across Europe. Analysis of the
      ESSCA Network 2002-2010.
AB  - BACKGROUND: Contact sensitization in children is more frequent than previously
      thought. METHODS: The ESSCA collected patch test data from 11 European countries
      aggregated to 4 European regions. RESULTS: Six thousand and eight patients aged 1
      16 years old with suspected allergic contact dermatitis were analyzed during a
      period of 8 years (2002-2010). The overall prevalence of at least one positive
      reaction to a hapten was 36.9%. The 10 most frequent haptens were as follows:
      nickel sulfate, cobalt chloride and potassium dichromate, neomycin sulfate,
      Myroxylon pereirae resin (balsam of Peru), para-phenylenediamine,
      chloromethylisothiazolinone/methylisothiazolinone 3:1, fragrance mix, lanolin
      alcohols, and colophony. No difference was found in the prevalence of at least
      one positive reaction to at least one hapten between boys and girls and between
      children with atopic dermatitis and children without. Children without atopic
      dermatitis, when compared with those with, had a significantly higher prevalence
      of contact sensitization for nickel sulfate (20.91% vs 16.87%, respectively), 4
      tert. butylphenol formaldehyde resin (1.61% vs. 0.7%), and para-phenylenediamine
      (2.49% vs. 1.3%). LIMITATIONS OF THE STUDY: Chamber loading is not an exact
      science and variation may occur between staff and departments. Interinstitution
      variations in readings can occur. A possible geographic confounder is that the
      southern regions tested more children in the younger age group. Relevance was not
      addressed due to difficulties in the application of a set of uniform definitions.
      CONCLUSIONS: Our study adds information on the most common contact allergens
      detected in children which could help to define a Standard European Pediatric
      Baseline Series.

PMID- 25939694
TI  - Straightforward synthesis of radioiodinated Cc-substituted o-carboranes: towards
      a versatile platform to enable the in vivo assessment of BNCT drug candidates.
AB  - Due to their high boron content and rich chemistry, dicarba-closo-dodecaboranes
      (carboranes) are promising building blocks for the development of drug candidates
      with application in Boron Neutron Capture Therapy. However, the non-invasive
      determination of their pharmacokinetic properties to predict therapeutic efficacy
      is still a challenge. Herein, we have reported the unprecedented preparation of
      mono-[(125)I] iodinated decaborane via a catalyst-assisted isotopic exchange.
      Subsequent reactions of the radiolabelled species with acetylenes in acetonitrile
      under microwave heating yield the corresponding (125)I-labelled, Cc-substituted o
      carboranes with good overall radiochemical yields in short reaction times. The
      same synthetic strategy was successfully applied to the preparation of (131)I
      labelled analogues, and further extension to other radioisotopes of iodine such
      as (124)I (positron emitter) or (123)I (gamma emitter) can be envisaged. Hence,
      the general strategy reported here is suitable for the preparation of a wide
      range of radiolabelled Cc-substituted o-carborane derivatives. The labelled
      compounds might be subsequently investigated in vivo by using nuclear imaging
      techniques such as Single Photon Emission Computerized Tomography or Positron
      Emission Tomography. 

PMID- 25939692
TI  - The etiology of cirrhosis is a strong determinant of brain reserve: A multimodal
      magnetic resonance imaging study.
AB  - Poor brain reserve in alcoholic cirrhosis could worsen insight regarding disease
      severity and increase the patients' vulnerability toward further deterioration.
      The aim of this study was to analyze brain reserve in abstinent alcoholic
      cirrhotic (Alc) patients compared to nonalcoholic cirrhotic (Nalc) patients in
      the context of hepatic encephalopathy (HE) and to evaluate relative change in
      brain reserve between groups over time and before and after elective transjugular
      intrahepatic portosystemic shunt (TIPS) placement. The cross-sectional study
      included 46 Alc and 102 Nalc outpatients with or without HE. Cognitive tests were
      followed by magnetic resonance imaging (MRI), including proton magnetic resonance
      spectroscopy (1 H-MRS), diffusion tensor imaging, and T1-weighted imaging. The
      prospective study included 1H-MRS on a subset of 10 patients before and after
      TIPS placement. Another subset of 26 patients underwent (1) H-MRS at least 1 year
      apart. For the cross-sectional study, Alc patients were worse on cognitive tests
      than Nalc patients. MRI results suggest a greater effect of hyperammonemia, brain
      edema, and significantly higher cortical damage in Alc as compared to Nalc
      patients. The effect of HE status on cognitive tests and brain reserve was more
      marked in the Nalc than in the Alc group. For the TIPS study, Nalc patients
      showed a greater adverse relative change after TIPS compared to the Alc group. At
      1-year follow-up, both groups remained stable between the 2 visits. However, Alc
      patients continued to show poor brain reserve compared to Nalc patients over
      time. In conclusion, Alc patients, despite abstinence, have a poor brain reserve,
      whereas Nalc patients have a greater potential for brain reserve deterioration
      after HE and TIPS. Information regarding the brain reserve in cirrhosis could
      assist medical teams to refine their communication and monitoring strategies for
      different etiologies.

PMID- 25939695
TI  - Repeatability of evolution on epistatic landscapes.
AB  - Evolution is a dynamic process. The two classical forces of evolution are
      mutation and selection. Assuming small mutation rates, evolution can be predicted
      based solely on the fitness differences between phenotypes. Predicting an
      evolutionary process under varying mutation rates as well as varying fitness is
      still an open question. Experimental procedures, however, do include these
      complexities along with fluctuating population sizes and stochastic events such
      as extinctions. We investigate the mutational path probabilities of systems
      having epistatic effects on both fitness and mutation rates using a theoretical
      and computational framework. In contrast to previous models, we do not limit
      ourselves to the typical strong selection, weak mutation (SSWM)-regime or to
      fixed population sizes. Rather we allow epistatic interactions to also affect
      mutation rates. This can lead to qualitatively non-trivial dynamics. Pathways,
      that are negligible in the SSWM-regime, can overcome fitness valleys and become
      accessible. This finding has the potential to extend the traditional predictions
      based on the SSWM foundation and bring us closer to what is observed in
      experimental systems. 

PMID- 25939693
TI  - Ischaemia-modified albumin: a marker of bacterial infection in hospitalized
      patients with cirrhosis.
AB  - BACKGROUND & AIMS: Patients with cirrhosis present structural changes of human
      serum albumin (HSA) affecting non-oncotic functions. Ischaemia-modified albumin
      (IMA), which reflects the capacity to bind cobalt, has been associated to patient
      mortality during acute-on-chronic liver failure. This study aimed to assess
      whether circulating IMA is elevated in advanced cirrhosis and its relationship
      with severity of cirrhosis and specific complications. METHODS: A total of 127
      cirrhotic patients hospitalized for an acute complication of the disease and 44
      healthy controls were enrolled. Plasma IMA and IMA to albumin ratio (IMAr) were
      measured with a cobalt-binding assay. HSA isoforms carrying post-transcriptional
      molecular changes were assessed with HPLC-ESI-MS. The effect of endotoxemia on
      IMA was evaluated in rats with CCl4 -cirrhosis. RESULTS: IMA/IMAr is
      significantly higher in cirrhotic patients than in controls, but no correlations
      were found with prognostic scores. IMA did not correlate with the altered HSA
      isoforms. Ascites, renal impairment and hepatic encephalopathy did not influence
      IMA/IMAr levels. In contrast, IMA/IMAr is significantly higher in infected than
      non-infected patients. ROC curves showed that IMA/IMAr had similar discriminating
      performances for bacterial infection as C-reactive protein (CRP). Moreover, CRP
      and IMA were independently associated with bacterial infection. Consistently,
      endotoxin injection significantly increased IMA in cirrhotic, but not in healthy
      rats. CONCLUSIONS: IMA is elevated in patients with advanced cirrhosis. The IMA
      level does not correlate with disease severity scores, but it is specifically
      associated to bacterial infection, showing a discriminating performance similar
      to CRP. Further investigations to assess IMA as a novel diagnostic test for
      bacterial infection are advocated.

PMID- 25939696
TI  - Correction: Real-space evidence of the equilibrium ordered bicontinuous double
      diamond structure of a diblock copolymer.
AB  - Correction for 'Real-space evidence of the equilibrium ordered bicontinuous
      double diamond structure of a diblock copolymer' by C. Y. Chu et al., Soft
      Matter, 2015, 11, 1871-1876. 

PMID- 25939697
TI  - T2 relaxation time post febrile status epilepticus predicts cognitive outcome.
AB  - Evidence from animal models and patient data indicates that febrile status
      epilepticus (FSE) in early development can result in permanently diminished
      cognitive abilities. To understand the variability in cognitive outcome following
      FSE, we used MRI to measure dynamic brain metabolic responses to the induction of
      FSE in juvenile rats. We then compared these measurements to the ability to learn
      an active avoidance spatial task weeks later. T2 relaxation times were
      significantly lower in FSE rats that were task learners in comparison to FSE non
      learners. While T2 time in whole brain held the greatest predictive power, T2 in
      hippocampus and basolateral amygdala were also excellent predictors. These signal
      differences in response to FSE indicate that rats that fail to meet metabolic and
      oxygen demand are more likely to develop spatial cognition deficits. Place cells
      from FSE non-learners had significantly larger firing fields and higher in-field
      firing rate than FSE learners and control animals and imply increased
      excitability in the pyramidal cells of FSE non-learners. These findings suggest a
      mechanistic cause for the spatial memory deficits in active avoidance and are
      relevant to other acute neurological insults in early development where cognitive
      outcome is a concern. 

PMID- 25939699
TI  - Attention is critical for spatial auditory object formation.
AB  - The precedence effect provides a novel way to examine the role of attention in
      auditory object formation. When presented with two identical sounds from
      different locations separated by a short stimulus onset asynchrony (SOA),
      listeners report a single auditory object at the location of the lead sound. When
      the SOA is above the echo threshold, listeners report hearing two auditory
      objects with different locations. Event-related potential (ERP) studies have
      shown that the number of perceived auditory objects is reflected in an object
      related negativity (ORN) 100-250 ms after onset and in a posterior late
      positivity (LP) 300-500 ms after onset. In the present study, we tested whether
      these ERP effects are modulated by attention by presenting lead/lag click pairs
      at and around listeners' echo thresholds, while in separate blocks the listeners
      (1) attended to the sounds and reported whether the lag sound was a separate
      source, and (2) performed a two-back visual task. When attention was directed
      away from the sounds, neither the ORN nor the LP observed in the attend condition
      was evident. Instead, unattended click pairs above the echo threshold elicited an
      anterior positivity 250-450 ms after onset. However, an effect resembling an ORN
      was found in comparing the ERPs elicited by unattended click pairs with SOAs
      below the attended echo threshold, indicating that the echo threshold may have
      been lowered when attention was directed away from the sounds. These results
      suggest that attention modulates early perceptual processes that are critical for
      auditory object formation. 

PMID- 25939700
TI  - Limited capacity for memory tasks with multiple features within a single object.
AB  - Memory for multiple features might be limited by the number of features, the
      number of objects, or both. To focus on the role of features, we tested memory
      for a variable number of features within a single object. Subjects studied a
      single ellipse that varied in four features: size, orientation, contrast, and
      position. We conducted two experiments that differed in how memory was tested. If
      performance is limited only by the number of objects to be remembered, there
      should be no effect of the number of relevant features within a single object.
      Instead, for both experiments, the proportion correct was lower when four
      features had to be remembered rather than one. The magnitude of these effects
      varied with the details of the two experiments. Although similar results have
      been reported for experiments using multiple objects, the present experiments are
      some of the first to have demonstrated such an effect for a single object. This
      result is inconsistent with theories in which visual memory has a discrete limit
      on the number of stored objects, and no limit on the stored features within an
      object. Instead, it seems likely that objects and features both play roles in
      limiting performance in memory tasks. 

PMID- 25939701
TI  - Recognition of letters displayed as briefly flashed dot patterns.
AB  - Complex shapes can be identified (named) when only the outer boundary of the
      shape is represented by discrete dots and with the dots being displayed for a
      duration lasting only a few microseconds (MUs). This line of work is extended
      here to include recognition of letters with 10 MUs flashes as a means to study
      visible persistence and information persistence. The first two studies were
      designed to assess visible persistence. Models were derived that quantified how
      recognition changed as a function of flash intensity. Then each letter was
      displayed twice, each at a near-threshold level of intensity and varying the
      interval between flashes. The second flash was able to boost the influence of the
      first flash for about 100 ms. This corresponds to the duration that a brief flash
      will remain visible, so these conditions likely were producing visible
      persistence. Information persistence was studied by manipulating dot density of
      the letter patterns. Recognition declined as the density of dots in each letter
      pattern was reduced. When two complimentary low-density samples were flashed,
      there was summation of their influence that declined to an asymptote in about 200
      ms, and then remained above the one-flash control out to the maximum test
      interval of 1 s. The summation of high-salience, low-density dot patterns over
      such a long interval likely reflects both iconic memory persistence and access to
      working memory.

PMID- 25939698
TI  - Enhanced meta-analysis and replication studies identify five new psoriasis
      susceptibility loci.
AB  - Psoriasis is a chronic autoimmune disease with complex genetic architecture.
      Previous genome-wide association studies (GWAS) and a recent meta-analysis using
      Immunochip data have uncovered 36 susceptibility loci. Here, we extend our
      previous meta-analysis of European ancestry by refined genotype calling and
      imputation and by the addition of 5,033 cases and 5,707 controls. The combined
      analysis, consisting of over 15,000 cases and 27,000 controls, identifies five
      new psoriasis susceptibility loci at genome-wide significance (P<5 * 10(-8)). The
      newly identified signals include two that reside in intergenic regions (1q31.1
      and 5p13.1) and three residing near PLCL2 (3p24.3), NFKBIZ (3q12.3) and CAMK2G
      (10q22.2). We further demonstrate that NFKBIZ is a TRAF3IP2-dependent target of
      IL-17 signalling in human skin keratinocytes, thereby functionally linking two
      strong candidate genes. These results further integrate the genetics and
      immunology of psoriasis, suggesting new avenues for functional analysis and
      improved therapies. 

PMID- 25939702
TI  - Molecular spectrum of alpha-globin gene mutations in the Aegean region of Turkey:
      first observation of three alpha-globin gene mutations in the Turkish population.
AB  - Molecular test results of 231 individuals referred to our molecular genetics
      laboratory for analysis of alpha-globin gene mutations between the years 2007 and
      2013 were evaluated. Analysis of alpha-thalassemia gene mutations was performed
      using reverse dot-blot hybridisation, which includes 21 common mutations. Twelve
      distinct alpha-thalassemia mutations and 23 different genotypes have been
      detected in the Aegean region of Turkey. The most frequent mutations were 
      alpha3.7 (52.28 %), -(alpha)20.5 (14.74 %), --MED (10.53 %), and alphaPA-1alpha
      (8.77 %). Three alpha-thalassemia mutations (alphacd142alpha, --SEA, and
      alphaICalpha), which are more prevalent in Southeast Asia, are identified for the
      first time in Turkey in this study. We find that a broad spectrum of alpha
      thalassemia mutations is present in the Aegean region of Turkey. The results
      obtained in this study may help inform decisions in the design and implementation
      of prevention strategies and diagnostic approaches.

PMID- 25939703
TI  - JARID2 inhibits leukemia cell proliferation by regulating CCND1 expression.
AB  - It has recently been shown that JARID2 contributes to the malignant character of
      solid tumors, such as epithelial-mesenchymal transition in lung and colon cancer
      cell lines, but its role in leukemia progression is unexplored. In this study, we
      explored the effect and underlying molecular mechanism of JARID2 on leukemia cell
      proliferation. Real-time PCR and Western assay were carried out to detect JARID2
      and CCND1 expression. Cell number and cell cycle change were detected using
      hemocytometer and flow cytometry, and a ChIP assay was utilized to investigate
      JARID2 and H3K27me3 enrichment on the CCND1 promoter. JARID2 is down-regulated in
      B-chronic lymphocytic leukemia (B-CLL) and acute monocytic leukemia (AMOL), and
      knockdown of JARID2 promotes leukemia cell proliferation via acceleration of the
      G1/S transition. Conversely, ectopic expression of JARID2 inhibits these
      malignant phenotypes. Mechanistic studies show that JARID2 negatively regulates
      CCND1 expression by increasing H3K27 trimethylation on the CCND1 promoter. Our
      findings indicate that JARID2 is a negative regulator of leukemia cell
      proliferation, and functions as potential tumor suppressor in leukemia. 

PMID- 25939704
TI  - Bone geometry, bone mineral density, and micro-architecture in patients with
      myelofibrosis: a cross-sectional study using DXA, HR-pQCT, and bone turnover
      markers.
AB  - Primary myelofibrosis (MF) is a severe chronic myeloproliferative neoplasm,
      progressing towards a terminal stage with insufficient haematopoiesis and
      osteosclerotic manifestations. Whilst densitometry studies have showed MF
      patients to have elevated bone mineral density, data on bone geometry and micro
      structure assessed with non-invasive methods are lacking. We measured areal bone
      mineral density (aBMD) using dual-energy X-ray absorptiometry (DXA). Bone
      geometry, volumetric BMD, and micro-architecture were measured using high
      resolution peripheral quantitative computed tomography (HR-pQCT). We compared the
      structural parameters of bones by comparing 18 patients with MF and healthy
      controls matched for age, sex, and height. Blood was analysed for biochemical
      markers of bone turnover in patients with MF. There were no significant
      differences in measurements of bone geometry, volumetric bone mineral density,
      and micro-structure between MF patients and matched controls. Estimated bone
      stiffness and bone strength were similar between MF patients and controls. The
      level of pro-collagen type 1 N-terminal pro-peptide (P1NP) was significantly
      increased in MF, which may indicate extensive collagen synthesis, one of the
      major diagnostic criteria in MF. We conclude that bone mineral density, geometry,
      and micro-architecture in this cohort of MF patients are comparable with those in
      healthy individuals. 

PMID- 25939705
TI  - Evaluation of the role of lung volume and airway size and shape in supine
      predominant obstructive sleep apnoea patients.
AB  - BACKGROUND AND OBJECTIVE: This study aimed to evaluate the involvement of airway
      cross-sectional area and shape, and functional residual capacity (FRC), in the
      genesis of obstructive sleep apnoea (OSA) in patients with supine-predominant
      OSA. METHODS: Three groups were recruited: (i) supine OSA, defined as a supine
      apnoea-hyponoea index (AHI) at least twice that of the non-supine AHI; (ii) rapid
      eye movement (REM) OSA, defined as REM AHI at least twice the non-REM AHI and
      also selected to have supine AHI less than twice that of the non-supine AHI (i.e.
      to be non-positional); and (iii) no OSA, defined as an AHI less than five events
      per hour. The groups were matched for age, gender and body mass index. Patients
      underwent four-dimensional computed tomography scanning of the upper airway in
      the supine and lateral decubitus positions. FRC was measured in the seated,
      supine and lateral decubitus positions. RESULTS: Patients with supine OSA
      demonstrated a significant decrease in FRC of 340 mL (P = 0.026) when moving from
      the lateral to supine position compared to controls with no OSA, and REM OSA
      patients. We found no differences between groups in upper airway size and shape.
      However, all groups showed a significant change in airway shape with the
      velopharyngeal airway adopting a more elliptoid shape (with the long axis
      laterally oriented), with reduced anteroposterior diameter in the supine
      position. CONCLUSIONS: A fall in FRC when moving lateral to supine in supine OSA
      patients may be an important triggering factor in the generation of OSA in this
      patient group.

PMID- 25939706
TI  - Neonatal vitamin A supplementation associated with increased atopy in girls.
AB  - BACKGROUND: Neonatal vitamin A supplementation (NVAS) is currently being
      considered as policy in countries at risk of deficiency. A previous study
      suggested that NVAS may be associated with increased atopy. We examined the
      effect of NVAS on atopy by conducting long-term follow-up of a previous
      randomized controlled trial in Guinea-Bissau. METHODS: In 2002-2004, we
      randomized 4345 normal birthweight neonates to NVAS (50 000 IU retinyl palmitate)
      or placebo together with their Bacillus Calmette-Guerin vaccination. In 2013, we
      visited the 1692 (39%) children now aged 8-10 years who were still living in the
      study area, and 1478 (87%) were found at home. Provided consent, a skin prick
      test was performed, and history of allergic symptoms was recorded. Associations
      of NVAS and atopy (defined as skin prick test reaction of >=3 mm) were analysed
      using binomial regression. RESULTS: Of the 1430 children with a valid skin prick
      test, 228 (16%) were positive (more boys (20%) than girls (12%), P-value <
      0.0001). NVAS did not increase the overall risk of atopy (RR 1.10 [95% CI 0.87
      1.40]). However, NVAS was associated with significantly increased risk among
      females (RR 1.78 [1.17-2.72]) but not among males (0.86 [0.64-1.15], P-value for
      interaction between NVAS and gender = 0.005). Furthermore, NVAS was associated
      with increased risk of wheezing among females (RR 1.80 [1.03-3.17], but not among
      males, P-value for interaction = 0.05). CONCLUSION: The study corroborated
      previous observations; NVAS was associated with increased risk of atopy and
      wheezing, in this study only among females. Further studies on NVAS and atopy are
      warranted.

PMID- 25939707
TI  - Population pharmacokinetics of intravenous and oral panobinostat in patients with
      hematologic and solid tumors.
AB  - PURPOSE: The study aimed to characterize the population pharmacokinetics of
      panobinostat, a pan-deacetylase inhibitor that has demonstrated efficacy in
      combination with bortezomib and dexamethasone in patients with multiple myeloma.
      METHODS: A nonlinear mixed-effect model was used to fit plasma panobinostat
      concentration-time data collected from patients across 14 phase 1 and phase 2
      trials following either oral or intravenous (IV) administration. The model was
      used to estimate bioavailabilities of the two oral formulations and the effects
      of demographic and clinical covariates on the central volume of distribution and
      clearance of panobinostat. RESULTS: A total of 7834 samples from 581 patients
      were analyzed. Panobinostat pharmacokinetic parameters were best characterized by
      a three-compartment model with first-order absorption and elimination.
      Bioavailability was 21.4 %. Median clearance was 33.1 L/h. Interindividual
      variability in clearance was 74 %. For Caucasian patients of median age 61 years,
      area under the curve (AUC) decreased from 104 to 88 ng . h/mL as body surface
      area (BSA) increased from the first to third quartiles, 1.8 to 2.1 m(2). For
      Caucasian patients of median BSA 1.9 m(2), AUC decreased from 102 to 95 ng . h/mL
      as age increased from the first to third quartiles, 51 to 70 years. For patients
      of median BSA and median age, AUC ranged across the four race categories from 80
      to 116 ng . h/mL. Covariate analysis showed no impact on panobinostat clearance
      and volume by patients' sex, tumor type, kidney function, liver markers, or
      coadministered medications. However, separate analyses of dedicated studies have
      demonstrated effects of liver impairment and CYP3A4 inhibition. CONCLUSIONS:
      Although covariate analyses revealed significant effects of body size, age, and
      race on panobinostat pharmacokinetics, these effects were minor compared to the
      interindividual variability and therefore not clinically relevant when dosing
      panobinostat in populations similar to those studied.

PMID- 25939708
TI  - Pharmacokinetics of intravenous telavancin in healthy subjects with varying
      degrees of renal impairment.
AB  - PURPOSE: We evaluated the effect of renal impairment (RI) on the pharmacokinetics
      of telavancin and hydroxypropylbetadex (excipient in the telavancin drug
      product). METHODS: Adults with normal, mild, moderate or severe RI or end-stage
      renal disease (ESRD) receiving haemodialysis were included in two open-label,
      phase I studies of single-dose telavancin at 7.5 mg/kg (study A, n = 29) or 10
      mg/kg (study B, n = 43). Pharmacokinetic analysis of telavancin and
      hydroxypropylbetadex plasma concentration versus time was performed in these
      subjects. RESULTS: The results in studies A and B were similar: telavancin
      systemic exposure (area under the concentration-time curve from 0 to infinity
      [AUC0-infinity]) increased with RI. Telavancin half-life (h, mean +/- SD)
      increased in subjects with severe RI compared with subjects with normal renal
      function from 6.9 +/- 0.6 in study A and 6.5 +/- 0.9 in study B to 14.5 +/- 1.3
      and 11.8 +/- 6.7, respectively. Conversely, clearance (ml/h/kg, mean +/- SD)
      decreased in subjects with severe RI compared with subjects with normal renal
      function from 13.7 +/- 2.1 in study A and 17.0 +/- 3.2 in study B to 6.18 +/-
      0.63 and 6.5 +/- 1.5, respectively. Systemic exposures for hydroxypropylbetadex
      also increased with severity of RI. CONCLUSIONS: Results from two independent
      phase 1 studies suggest that dose adjustment of telavancin is required in
      subjects with varying degrees of RI.

PMID- 25939709
TI  - Risk of toxic epidermal necrolysis and Stevens-Johnson syndrome associated with
      benzodiazepines: a population-based cohort study.
AB  - PURPOSE: We aim to estimate the incidence of Stevens-Johnson syndrome (SJS) and
      toxic epidermal necrolysis (TEN) among tetrazepam users and compare it with
      benzodiazepine users in a Spanish primary care database (BIFAP). The incidence in
      the general population (GenPop) and among phenytoin new users (as a positive
      control) was also estimated. METHODS: We identified a cohort of GenPop free of
      SJS/TEN (N = 3,155,364). Cohort entry was the date after 1 year of register with
      the physician during 2001-2011. No age restrictions were applied. Patients were
      followed from entry up to the first of the following: a record of SJS/TEN
      (potential cases), death, end of information, or December 2011. History of
      potential cases were manually reviewed blinded to exposure and considered
      "probable" when diagnosed in referral reports. Three cohorts of patients newly
      prescribed with benzodiazepines (N = 531,813), tetrazepam (N = 343,568), or
      phenytoin (N = 4993) were extracted from the GenPop cohort. Incidence rate (cases
      per million person-years (py)) for the GenPop and cumulative incidence (per
      million new users) during the first 9 weeks after each drug prescription were
      computed. RESULTS: In the GenPop, 48 probable cases (38 SJS and 10 TEN) were
      identified (3.21/million py; 3.37 in men and 2.94 in women). In the
      benzodiazepines cohort, 2 probable TEN cases was identified (3.76/mill.). In the
      tetrazepam cohort, 1 probable SJS/TEN case was identified (2.91/mill.). In the
      phenytoin cohort, 4 probable cases (2 SJS and 2 TEN) were identified
      (801.12/mill.). CONCLUSIONS: The incidence of SJS/TEN in tetrazepam users was
      very rare and similar to benzodiazepines users. The incidence in the GenPop and
      among users of phenytoin agreed with the literature.

PMID- 25939710
TI  - Distribution of xanthine oxidase activity in a Nigerian population.
AB  - BACKGROUND: Xanthine oxidase (XO) is one of the two interconvertible forms of
      xanthine oxidoreductase and well-studied for its role in purine catabolism and
      that of other purine analogues, drugs especially. Our study investigated the
      incidence of polymorphism in phenotypes along with the influence of gender and
      age on enzyme activity in a Nigerian population. METHODS: Caffeine (110 mg) was
      administered to each of 129 healthy, unrelated subjects who were nonsmokers.
      Urine voided within 7 h after dosing was collected for a high-performance liquid
      chromatographic analysis of metabolites, and the urinary molar ratio of
      metabolites was used as marker for enzyme activity. Statistical analysis of data
      was carried out to identify the prevalent phenotypes and also assessed the
      influence of age and sex on enzyme activity. RESULT: A sevenfold variation in XO
      activity with a population mean (+/- SD) molar ratio of 0.43 +/- 0.15 and median
      (interquartile range) of 0.42 (0.16) was observed. Distinctly higher enzyme
      activity was also recorded in 8% of the study population, and there was no
      correlation (P > 0.05) between enzyme activity and the studied covariates.
      CONCLUSIONS: Our study confirmed the existence of polymorphism in xanthine
      oxidase activity in Nigerians and also the incidence of individuals with
      distinctly higher XO activity in the population.

PMID- 25939712
TI  - Management of a recurrent massive abdominal haemophilic pseudotumour with
      adjuvant radiotherapy.

PMID- 25939711
TI  - Steady-state pharmacokinetics of metformin is independent of the OCT1 genotype in
      healthy volunteers.
AB  - PURPOSE: The aim of the study was to determine the steady-state pharmacokinetics
      of metformin in healthy volunteers with different numbers of reduced-function
      alleles in the organic cation transporter 1 gene (OCT1). METHODS: The study was
      conducted as part of a randomized cross-over trial. Thirty-four healthy
      volunteers with known OCT1 genotypes (12 with two wild-type alleles, 13 with one
      and 9 with two reduced-function alleles) were included. In one of the study
      periods, they were titrated to steady-state with 1 g metformin twice daily.
      RESULTS: Neither AUC(0-12), C(max) nor Cl(renal) were statistically significantly
      affected by the number of reduced-function alleles (0, 1 or 2) in OCT1: (AUC(0
      12): 0, 1, 2: 14, 13 and 14 h ng/L (P = 0.61)); (C(max): 0, 1, 2: 2192, 1934 and
      2233 ng/mL, (P = 0.26)) and (Cl(renal): 0, 1, 2: 31, 28 and 30 L/h (P = 0.57))
      CONCLUSIONS: In a cohort of healthy volunteers, we found no impact of different
      OCT1 genotypes on metformin steady-state pharmacokinetics.

PMID- 25939713
TI  - RBM28, a protein deficient in ANE syndrome, regulates hair follicle growth via
      miR-203 and p63.
AB  - Alopecia-neurological defects-endocrinopathy (ANE) syndrome is a rare inherited
      hair disorder, which was shown to result from decreased expression of the RNA
      binding motif protein 28 (RBM28). In this study, we attempted to delineate the
      role of RBM28 in hair biology. First, we sought to obtain evidence for the direct
      involvement of RBM28 in hair growth. When RBM28 was downregulated in human hair
      follicle (HF) organ cultures, we observed catagen induction and HF growth arrest,
      indicating that RBM28 is necessary for normal hair growth. We also aimed at
      identifying molecular targets of RBM28. Given that an RBM28 homologue was
      recently found to regulate miRNA biogenesis in C. elegans and given the known
      pivotal importance of miRNAs for proper hair follicle development, we studied
      global miRNA expression profile in cells knocked down for RBM28. This analysis
      revealed that RBM28 controls the expression of miR-203. miR-203 was found to
      regulate in turn TP63, encoding the transcription factor p63, which is critical
      for hair morphogenesis. In conclusion, RBM28 contributes to HF growth regulation
      through modulation of miR-203 and p63 activity.

PMID- 25939714
TI  - Changes in the physiological parameters, fatty acid metabolism, and SCD activity
      and expression in juvenile GIFT tilapia (Oreochromis niloticus) reared at three
      different temperatures.
AB  - We evaluated the effects of rearing temperature on the composition of fatty acids
      and stearoyl-CoA desaturase (SCD) activity and gene expression in GIFT
      (genetically improved farmed tilapia) tilapia. Three triplicate groups of fish
      were reared for 40 days at 22, 28, or 34  degrees C. At the end of the trial, the
      final body weight of juveniles reared at 28  degrees C was higher than that of
      fish reared at 22 or 34  degrees C. Feed intake, feed efficiency, and the protein
      efficiency ratio were also higher at 28  degrees C. The fatty acid composition of
      muscle tissue differed significantly (P < 0.05) among the treatment groups. The
      content of SFA decreased with decreasing temperature, whereas the UFA content
      increased. We observed high levels of PUFA, particularly n-3 PUFAs, in fish
      reared at the lower temperature. Rearing at low temperature significantly (P <
      0.05) increased the expression and activity of the SCD gene. Increased SCD
      activity and gene expression can increase the biosynthesis of MUFAs in GIFT
      tilapia muscle. Additionally, cold acclimation can decrease the content of TC and
      TG in GIFT tilapia, which can help increase cold tolerance. 

PMID- 25939715
TI  - Physiological management of dietary deficiency in n-3 fatty acids by spawning
      Gulf killifish (Fundulus grandis).
AB  - Lipid dynamics of spawning fish are critical to the production of viable embryos
      and larvae. The present study utilized manipulation of dietary fatty acid (FA)
      profiles to examine the ability of spawning Gulf killifish (Fundulus grandis) to
      mobilize critical lipid components from somatic reserves or synthesize long-chain
      polyunsaturated FAs (LC-PUFAs) de novo from shorter-chain C18 precursors. An egg
      and multi-tissue evaluation of changes in FA concentrations across time after
      fish were switched from LC-PUFA-rich to LC-PUFA-deficient experimental diets was
      employed. The two experimental diets contained lipid sources which differed
      drastically in n-3 C18 FA content but had similar levels of n-6 C18 FAs. Discrete
      effects of dietary n-3 FAs can be analyzed because n-3 and n-6 represent distinct
      metabolic families which cannot be exchanged in vivo. Results indicate that a
      combination of mobilization and de novo synthesis is likely utilized to maintain
      physiologically required FA levels in critical tissues and embryos. Mobilization
      was supported by decreases in LC-PUFAs in somatic tissues and decreases in
      intraperitoneal fat content and liver mass. Evidence for biosynthesis was
      provided by a higher level of n-3 LC-PUFAs in the liver and ova of fish fed diets
      containing n-3 C18 precursors versus those fed diets with low levels of precursor
      FAs. The characteristic physiological plasticity of Gulf killifish is exemplified
      in the nutritional domain by its management of dietary FA deficiency. 

PMID- 25939716
TI  - Atypical teratoid rhabdoid tumor: long-term survival after chemoradiotherapy.
AB  - PURPOSE: Atypical teratoid rhabdoid tumors (ATRTs) arise from the central nervous
      system largely in the pediatric population. They portend a very poor prognosis
      with few long-term survivors. We describe a series of five cases at our
      institution. METHODS: We conducted a retrospective chart review and clinical
      follow-up. RESULTS: Three patients underwent chemoradiation after surgical
      resection; the two patients whose caretakers declined this therapy passed away
      soon after diagnosis. Chemoradiation included intravenous and intrathecal
      chemotherapy as well as intensity-modulated radiotherapy after resection. Of the
      patients receiving chemoradiation, two patients had infratentorial tumors, two
      had gross residual tumor after resection, and two were under the age of 3 years.
      The three patients receiving trimodality therapy remain clinically and
      symptomatically disease-free with follow-up times of 44, 46, and 55 months. Two
      of the patients have mild neuropsychiatric sequelae after therapy. CONCLUSIONS:
      Long-term, high-volume trials of ATRT are currently not published. We offer
      experience in successful long-term survival of this tumor treated with
      chemoradiotherapy.

PMID- 25939717
TI  - A comprehensive review of the sub-axial ligaments of the vertebral column: part
      II histology and embryology.
AB  - BACKGROUND: As important as the vertebral ligaments are in maintaining the
      integrity of the spinal column and protecting the contents of the spinal canal, a
      single detailed review of their histology and embryology is missing in the
      literature. METHODS: A literature search using online search engines was
      conducted. RESULTS: Single comprehensive reviews of the histology and embryology
      of the spinal ligaments are not found in the extant medical literature.
      CONCLUSIONS: This review will be useful to those who study or treat patients with
      pathology of the spine.

PMID- 25939718
TI  - Embolisation of pulmonary vasculature during endovascular therapy-a case report.
AB  - Systemic complications following liquid glue embolisation of intracranial pial
      arteriovenous fistulae (AVF) are uncommonly reported. We report a patient who had
      a pulmonary embolism of a liquid glue during endovascular treatment of a pial
      AVF. The patient had haemodynamic instability, pulmonary hypertension, increased
      alveolar dead space and increased brain natriuretic peptide levels. In addition
      to other supportive measures, her pulmonary hypertension was controlled with
      sildenafil. Ten months after the event, the patient had a considerable
      improvement of the clinical and laboratory variables and a significant
      radiographic resolution of the glue from the pulmonary circulation. 

PMID- 25939719
TI  - Technical note on hemispherotomy.

PMID- 25939720
TI  - Patatin-like phospholipase 3 (rs738409) gene polymorphism is associated with
      increased liver enzymes in obese adolescents and metabolic syndrome in all ages.
AB  - BACKGROUND: Obesity is associated with non-alcoholic fatty liver disease (NAFLD),
      and the patatin-like phospholipase 3 (PNPLA3) rs738409 (Ile148Met, C>G) gene
      polymorphism is one of the most important genetic determinants of NAFLD. Carriers
      have been reported to better respond to lifestyle modification. AIM: To
      investigate the effect of rs738409 on overweight/obese adolescents and adults
      with and without metabolic syndrome (MetS). METHODS: Two hundred and eighty-eight
      overweight/obese and 209 normal weight participants of the STYJOBS/EDECTA cohort
      (NCT00482924) were analysed for PNPLA3 genotypes. RESULTS: Compared to
      overweight/obese without MetS, in overweight/obese study participants with MetS,
      the presence of the G allele (148Met) was significantly higher (CC: 5.0% vs.
      9.2%, Spearman's correlation, 0.12; P = 0.038). Persons with CG (heterozygote for
      the risk allele) and with GG (homozygote for the risk allele) genotypes showed
      significantly higher ALT levels than those with CC genotypes. Even young
      individuals aged below 20 years had significantly increased ALT levels if they
      were homozygote with the G allele. CONCLUSIONS: The PNPLA3 rs738409 polymorphism
      is associated already in youths with increased ALT, and is more frequent in obese
      with MetS of all ages. Hence, overweight/obese rs738409 carriers should be
      identified early in life and treated with a rigorous life style intervention.

PMID- 25939721
TI  - A high-throughput microfluidic single-cell screening platform capable of
      selective cell extraction.
AB  - Microfluidic devices and lab-on-a-chip technologies have been extensively used in
      high-throughput single-cell analysis applications using their capability to
      precisely manipulate cells as well as their microenvironment. Although
      significant technological advances have been made in single-cell capture,
      culture, and analysis techniques, most microfluidic systems cannot selectively
      retrieve samples off-chip for additional examinations. Being able to retrieve
      target cells of interest from large arrays of single-cell culture compartments is
      especially critical in achieving high-throughput single-cell screening
      applications, such as a mutant library screening. We present a high-throughput
      microfluidic single-cell screening platform capable of investigating cell
      properties, such as growth and biomolecule production, followed by selective
      extraction of particular cells showing desired traits to off-chip reservoirs for
      sampling or further analysis. The developed platform consists of 1024 single-cell
      trapping/culturing sites, where opening and closing of each trap can be
      individually controlled with a microfluidic OR logic gate. By opening only a
      specific site out of the 1024 trapping sites and applying backflow, particular
      cells of interest could be selectively released and collected off-chip. Using a
      unicellular microalga Chlamydomonas reinhardtii, single-cell capture and
      selective cell extraction capabilities of the developed platform were
      successfully demonstrated. The growth profile and intracellular lipid
      accumulation of the cells were also analyzed inside the platform, where 6-8 hours
      of doubling time and on-chip stained lipid bodies were successfully identified,
      demonstrating the compatibility of the system for cell culture and fluorescent
      tagging assays. 

PMID- 25939722
TI  - Influence of different surface modification treatments on silk biotextiles for
      tissue engineering applications.
AB  - Biotextile structures from silk fibroin have demonstrated to be particularly
      interesting for tissue engineering (TE) applications due to their high mechanical
      strength, interconnectivity, porosity, and ability to degrade under physiological
      conditions. In this work, we described several surface treatments of knitted silk
      fibroin (SF) scaffolds, namely sodium hydroxide (NaOH) solution, ultraviolet
      radiation exposure in an ozone atmosphere (UV/O3) and oxygen (O2) plasma
      treatment followed by acrylic acid (AAc), vinyl phosphonic acid (VPA), and vinyl
      sulfonic acid (VSA) immersion. The effect of these treatments on the mechanical
      properties of the textile constructs was evaluated by tensile tests in dry and
      hydrated states. Surface properties such as morphology, topography, wettability
      and elemental composition were also affected by the applied treatments. The in
      vitro biological behavior of L929 fibroblasts revealed that cells were able to
      adhere and spread both on the untreated and surface-modified textile constructs.
      The applied treatments had different effects on the scaffolds' surface
      properties, confirming that these modifications can be considered as useful
      techniques to modulate the surface of biomaterials according to the targeted
      application.

PMID- 25939723
TI  - Endovascular Therapy Proven for Stroke - Finally!
AB  - Cardiologists often remark that the field of ischaemic stroke follows in the
      footsteps of cardiology, just one to two decades later. In the case of
      endovascular reperfusion therapies this certainly seems to have been the case but
      there are now multiple positive randomised trials establishing the benefit of
      mechanical thrombectomy over and above standard care, which included intravenous
      alteplase in most cases. We will outline the new evidence, contrast the recent
      trials with the earlier negative studies and discuss some important differences
      between acute myocardial infarction and ischaemic stroke and the techniques
      required to treat them. 

PMID- 25939724
TI  - Examining motivations and barriers for attending maintenance community-based
      cardiac rehabilitation using the health-belief model.
AB  - BACKGROUND: Reasons for low attendance at maintenance cardiac rehabilitation (CR)
      programs remain largely unknown. Using the Health Belief Model as a theoretical
      framework, this study compared the motivations and barriers for attending a
      community-based CR maintenance program in high attenders (HA), low attenders (LA)
      and non-attenders (NA) with coronary artery disease (CAD). METHODS: Forty-four
      older adults with CAD (70.5% males; age: 72.7+/-6.9 years; 11 HA, 16 LA and 17
      NA) completed questionnaires examining reasons for attending CR: perceived threat
      (symptoms of CAD; the Revised Illness Perception Questionnaire), perceived
      benefits (Multi-dimensional Outcomes Expectations for Exercise Scale), perceived
      barriers (Cardiac Rehabilitation Barriers Scale) and cues to action
      questionnaire. RESULTS: Sociodemographic characteristics and perceived threat
      were not different between the groups. Compared to LA and NA, HA perceived
      greater social and physical (vs NA only) benefits of participation in maintenance
      CR and had fewer barriers to attending (all p<0.05). The CR program newsletter,
      personal health concerns and others having heart problems were stronger cues to
      action for HA versus NA (all p<0.05). CONCLUSIONS: Participants perceived greater
      benefits from attending CR, had fewer barriers and perceived stronger cues to
      action compared to non-attenders. Promoting CR maintenance programs should
      emphasise physical and social benefits and provide encouragement.

PMID- 25939725
TI  - Asymmetric Synthesis of 1,3-Butadienyl-2-carbinols by the Homoallenylboration of
      Aldehydes with a Chiral Phosphoric Acid Catalyst.
AB  - Asymmetric C(sp)-C(sp(2)) bond formation to give enantiomerically enriched 1,3
      butadienyl-2-carbinols occurred through a homoallenylboration reaction between a
      2,3-dienylboronic ester and aldehydes under the catalysis of a chiral phosphoric
      acid (CPA). A diverse range of enantiomerically enriched butadiene-substituted
      secondary alcohols with aryl, heterocyclic, and aliphatic substituents were
      synthesized in very high yield with high enantioselectivity. Preliminary density
      functional theory (DFT) calculations suggest that the reaction proceeds via a
      cyclic six-membered chairlike transition state with essential hydrogen-bond
      activation in the allene reagent. The catalytic reaction was amenable to the gram
      scale synthesis of a chiral alkyl butadienyl adduct, which was converted into an
      interesting optically pure compound bearing a benzo-fused spirocyclic
      cyclopentenone framework.

PMID- 25939726
TI  - Levodopa-carbidopa intrajejunal gel in advanced Parkinson disease with "on"
      freezing of gait.
AB  - Freezing of gait is a common and disabling disorder in advanced Parkinson's
      disease (PD). The relationship with dopaminergic medication is complex and often
      non-linear, thus freezing may occur even when the core parkinsonian features
      (tremor, rigidity and bradykinesia) appear optimally controlled. We evaluated the
      effect of Levodopa-carbidopa intrajejunal gel in a group of seven non-demented PD
      patients with prominent episodes of freezing refractory to adjustments of oral
      therapy. Clinical assessments were performed in the best "on" state before
      starting Levodopa-carbidopa intrajejunal gel, while patients were on their
      standard oral Levodopa (O-LD), and infusion treatment. The main outcome measures
      were change in freezing of gait (FOG) Questionnaire and UPDRS motor score. FOG
      Questionnaire and UPDRS subscores related to gait and postural stability
      significantly improved during Levodopa-carbidopa intrajejunal gel infusion in all
      patients compared to O-LD treatment. In four out of seven patients, the Levodopa
      carbidopa intrajejunal gel dose was equivalent or slightly higher but in three
      patients was lower compared to O-LD dose recorded at baseline visit. In selected
      patients, Levodopa-carbidopa intrajejunal gel may improve freezing refractory to
      oral dopaminergic therapy. 

PMID- 25939729
TI  - Synthesis and modeling of uniform complex metal oxides by close-proximity
      atmospheric pressure chemical vapor deposition.
AB  - A close-proximity atmospheric pressure chemical vapor deposition (AP-CVD) reactor
      is developed for synthesizing high quality multicomponent metal oxides for
      electronics. This combines the advantages of a mechanically controllable
      substrate-manifold spacing and vertical gas flows. As a result, our AP-CVD
      reactor can rapidly grow uniform crystalline films on a variety of substrate
      types at low temperatures without requiring plasma enhancements or low pressures.
      To demonstrate this, we take the zinc magnesium oxide (Zn(1-x)Mg(x)O) system as
      an example. By introducing the precursor gases vertically and uniformly to the
      substrate across the gas manifold, we show that films can be produced with only
      3% variation in thickness over a 375 mm(2) deposition area. These thicknesses are
      significantly more uniform than for films from previous AP-CVD reactors. Our
      films are also compact, pinhole-free, and have a thickness that is linearly
      controllable by the number of oscillations of the substrate beneath the gas
      manifold. Using photoluminescence and X-ray diffraction measurements, we show
      that for Mg contents below 46 at. %, single phase Zn(1-x)Mg(x)O was produced. To
      further optimize the growth conditions, we developed a model relating the
      composition of a ternary oxide with the bubbling rates through the metal
      precursors. We fitted this model to the X-ray photoelectron spectroscopy measured
      compositions with an error of Deltax = 0.0005. This model showed that the
      incorporation of Mg into ZnO can be maximized by using the maximum bubbling rate
      through the Mg precursor for each bubbling rate ratio. When applied to poly(3
      hexylthiophene-2,5-diyl) hybrid solar cells, our films yielded an open-circuit
      voltage increase of over 100% by controlling the Mg content. Such films were
      deposited in short times (under 2 min over 4 cm(2)).

PMID- 25939728
TI  - Case-fatality and disability in the Tanzanian Stroke Incidence Project cohort.
AB  - OBJECTIVES: The burden of stroke on healthcare services in sub-Saharan Africa
      (SSA) is increasing. However, long-term outcomes from stroke in SSA are not well
      described. We aimed to investigate case-fatality and health outcomes for stroke
      survivors at 7- to 10-year follow-up. MATERIALS AND METHODS: The Tanzanian Stroke
      Incidence Project (TSIP) recruited incidence stroke cases between 2003 and 2006.
      We followed up cases in 2013, recording date of death in those who had died.
      RESULTS: Of 130 stroke cases included in this study, case-fatality and date of
      death data were available for 124 at 7-10 years post-stroke. Of these, 102
      (82.3%) had died by 7 years post-stroke. Functional disability, as measured by
      the Barthel index immediately post-stroke, was a significant predictor of case
      fatality at seven-year follow-up with those with severe disability having an
      almost four-fold increase in the odds of death compared with those with no, mild
      or moderate disability. CONCLUSIONS: Case-fatality rates are higher than reported
      in high-income countries, with post-stroke disability a significant predictor of
      death. Sustainable interventions to reduce post-stroke disability in this setting
      should be investigated.

PMID- 25939730
TI  - Three-year-olds express suspense when an agent approaches a scene with a false
      belief.
AB  - Research on early false belief understanding has entirely relied on affect
      neutral measures such as judgments (standard tasks), attentional allocation
      (looking duration, preferential looking, anticipatory looking), or active
      intervention. We used a novel, affective measure to test whether preschoolers
      affectively anticipate another's misguided acts. In two experiments, 3-year-olds
      showed more expressions of suspense (by, e.g. brow furrowing or lip biting) when
      they saw an agent approach a scene with a false as opposed to a true belief
      (Experiment 1) or ignorance (Experiment 2). This shows that the children
      anticipated the agent's surprise and disappointment when encountering reality.
      The findings suggest that early implicit knowledge of false beliefs includes
      anticipations of the affective implications of erring. This vital dimension of
      beliefs should no longer be ignored in research on early theory of mind. 

PMID- 25939727
TI  - Procedural validity of the AUDADIS-5 depression, anxiety and post-traumatic
      stress disorder modules: Substance abusers and others in the general population.
AB  - BACKGROUND: Little is known about the procedural validity of lay-administered,
      fully-structured assessments of depressive, anxiety and post-traumatic stress
      (PTSD) disorders in the general population as determined by comparison with
      clinical re-appraisal, and whether this differs between current regular substance
      abusers and others. We evaluated the procedural validity of the Alcohol Use
      Disorder and Associated Disabilities Interview Schedule, DSM-5 Version (AUDADIS
      5) assessment of these disorders through clinician re-interviews. METHODS: Test
      retest design among respondents from the National Epidemiologic Survey on Alcohol
      and Related Conditions-III (NESARC-III): (264 current regular substance abusers,
      447 others). Clinicians blinded to AUDADIS-5 results administered the semi
      structured Psychiatric Research Interview for Substance and Mental Disorders, DSM
      5 version (PRISM-5). AUDADIS-5/PRISM-5 concordance was indicated by kappa (kappa)
      for diagnoses and intraclass correlation coefficients (ICC) for dimensional
      measures (DSM-5 symptom or criterion counts). Results were compared between
      current regular substance abusers and others. RESULTS: AUDADIS-5 and PRISM-5
      concordance for DSM-5 depressive disorders, anxiety disorders and PTSD was
      generally fair to moderate (kappa=0.24-0.59), with concordance on dimensional
      scales much better (ICC=0.53-0.81). Concordance differed little between regular
      substance abusers and others. CONCLUSIONS: AUDADIS-5/PRISM-5 concordance
      indicated procedural validity for the AUDADIS-5 among substance abusers and
      others, suggesting that AUDADIS-5 diagnoses of DSM-5 depressive, anxiety and PTSD
      diagnoses are informative measures in both groups in epidemiological studies. The
      stronger concordance on dimensional measures supports the current movement toward
      dimensional psychopathology measures, suggesting that such measures provide
      important information for research in the NESARC-III and other datasets, and
      possibly for clinical purposes as well.

PMID- 25939731
TI  - Provision of NHS generalist and specialist services to care homes in England:
      review of surveys.
AB  - BACKGROUND: The number of beds in care homes (with and without nurses) in the
      United Kingdom is three times greater than the number of beds in National Health
      Service (NHS) hospitals. Care homes are predominantly owned by a range of
      commercial, not-for-profit or charitable providers and their residents have high
      levels of disability, frailty and co-morbidity. NHS support for care home
      residents is very variable, and it is unclear what models of clinical support
      work and are cost-effective. OBJECTIVES: To critically evaluate how the NHS works
      with care homes. METHODS: A review of surveys of NHS services provided to care
      homes that had been completed since 2008. It included published national surveys,
      local surveys commissioned by Primary Care organisations, studies from charities
      and academic centres, grey literature identified across the nine government
      regions, and information from care home, primary care and other research
      networks. Data extraction captured forms of NHS service provision for care homes
      in England in terms of frequency, location, focus and purpose. RESULTS: Five
      surveys focused primarily on general practitioner services, and 10 on specialist
      services to care home. Working relationships between the NHS and care homes lack
      structure and purpose and have generally evolved locally. There are wide
      variations in provision of both generalist and specialist healthcare services to
      care homes. Larger care home chains may take a systematic approach to both
      organising access to NHS generalist and specialist services, and to supplementing
      gaps with in-house provision. Access to dental care for care home residents
      appears to be particularly deficient. CONCLUSIONS: Historical differences in
      innovation and provision of NHS services, the complexities of collaborating
      across different sectors (private and public, health and social care, general and
      mental health), and variable levels of organisation of care homes, all lead to
      persistent and embedded inequity in the distribution of NHS resources to this
      population. Clinical commissioners seeking to improve the quality of care of care
      home residents need to consider how best to provide fair access to health care
      for older people living in a care home, and to establish a specification for
      service delivery to this vulnerable population.

PMID- 25939732
TI  - [Not Available].

PMID- 25939733
TI  - [Not Available].

PMID- 25939734
TI  - Chronic expanding hematoma on the linea alba after breast reconstruction using
      free muscle-sparing transverse rectus abdominis musculocutaneous (TRAM) flap.

PMID- 25939736
TI  - Certification and education as determinants of nurse practitioner scope of
      practice: An investigation of the rules and regulations defining NP scope of
      practice in the United States.
AB  - PURPOSE AND BACKGROUND: In 2008, a consortium of advanced practice nursing
      organizations authored the Consensus Model for APRN Regulation: Licensure,
      Accreditation, Certification, and Education. The document's aim is to provide
      guidance for states to adopt uniformity in the regulation of advanced practice
      registered nurse roles. Despite a target date to complete that work by 2015,
      there remains an extensive amount of variation in how states define the scope of
      practice (SOP) for nurse practitioners (NPs). DATA SOURCES: Based on the National
      Council of State Boards of Nursing online database, state (N = 51 [includes the
      District of Columbia]) NP practice acts and/or rules and regulations documents
      were examined for language describing SOP for NPs consistent with the language of
      the advanced practice registered nurse (APRN) Consensus Model. CONCLUSIONS:
      Results indicated that 18 states and the District of Columbia (37%) had specific
      regulations defining NP SOP by certification and/or educational preparation while
      23 (45%) did not. The remaining nine states (18%) had SOP regulations that were
      interpreted as being ambiguous in relation to certification and/or educational
      preparation. IMPLICATIONS FOR PRACTICE: The findings suggest much work is needed
      to ensure NP SOP accurately reflects NP board-certification and graduate
      educational preparation.

PMID- 25939735
TI  - S-Nitrosated Polypropylene Sulfide Nanoparticles for Thiol-Dependent
      Transnitrosation and Toxicity Against Adult Female Filarial Worms.
AB  - A synthetic polymer nanoparticle formulation utilizing the physiological
      nitrosothiol chemistry for nitric oxide delivery is shown. Toxicity of S-nitroso
      nanoparticles against adult female Brugia malayi worms, which are responsible for
      lymphatic filariasis, is dependent on nitric oxide release through
      transnitrosation as S-nitrosocysteine, a potent endogenous nitric oxide donor. 

PMID- 25939737
TI  - Rearrangement and depletion of folate in human skin by ultraviolet radiation.

PMID- 25939738
TI  - Insight into unresolved complex mixtures of aromatic hydrocarbons in heavy oil
      via two-dimensional gas chromatography coupled with time-of-flight mass
      spectrometry analysis.
AB  - The aromatic hydrocarbon fractions of five crude oils representing a natural
      sequence of increasing degree of biodegradation from the Liaohe Basin, NE, China,
      were analyzed using conventional gas chromatography-mass spectrometry (GC-MS) and
      comprehensive two-dimensional gas chromatography (GC*GC). Because of the limited
      peak capability and low resolution, compounds in the aromatic fraction of a
      heavily biodegraded crude oil that were analyzed by GC-MS appeared as unresolved
      complex mixtures (UCMs) or GC "humps". They could be separated based on their
      polarity by GC*GC. UCMs are composed mainly of aromatic biomarkers and aromatic
      hydrocarbons with branched alkanes or cycloalkanes substituents. The quantitative
      results achieved by GC*GC-FID were shown that monoaromatic hydrocarbons account
      for the largest number and mass of UCMs in the aromatic hydrocarbon fraction of
      heavily biodegraded crude oil, at 45% by mass. The number and mass of diaromatic
      hydrocarbons ranks second at 33% by mass, followed by the aromatic biomarker
      compounds, triaromatic, tetraaromatic, and pentaaromatic hydrocarbons, that
      account for 10%, 6%, 1.5%, and 0.01% of all aromatic compounds by mass,
      respectively. In the heavily biodegraded oil, compounds with monocyclic
      cycloalkane substituents account for the largest proportion of mono- and
      diaromatic hydrocarbons, respectively. The C4-substituted compounds account for
      the largest proportion of naphthalenes and the C3-substituted compounds account
      for the largest proportion of phenanthrenes, which is very different from non
      biodegraded, slightly biodegraded, and moderately biodegraded crude oil. It is
      inferred that compounds of monoaromatic, diaromatic and triaromatic hydrocarbons
      are affected by biodegradation, that compounds with C1-, C2-substituents are
      affected by the increase in degree of biodegradation, and that their relative
      content decreased, whereas compounds with C3-substituents or more were affected
      slightly or unaffected, and their relative content also increased. The varying
      regularity of relative content of substituted compounds may be used to reflect
      the degree of degradation of heavy oil. Moreover, biomarkers for the aromatic
      hydrocarbons of heavily biodegraded crude oil are mainly aromatic steranes,
      aromatic secohopanes, aromatic pentacyclotriterpanes, and benzohopanes. According
      to resultant data, aromatic secohopanes could be used as a specific marker
      because of their relatively high concentration. This aromatic compound analysis
      of a series of biodegraded crude oil is useful for future research on the
      quantitative characterization of the degree of biodegradation of heavy oil,
      unconventional oil maturity evaluation, oil source correlation, depositional
      environment, and any other geochemical problems. 

PMID- 25939740
TI  - Zinc Sulfide Nanosheet-Based Hybrid Superlattices with Tunable Architectures
      Showing Enhanced Photoelectrochemical Properties.
AB  - Zinc sulfide nanosheet-based hybrid superlattices with tunable periodicities and
      rod-like or tubular morphologies are constructed by the spontaneous assembly of
      nanosheets as they grow in amine solution. The as-prepared architectures can be
      used as an enhanced electrode for photocurrent response and converted to other
      functional materials. 

PMID- 25939739
TI  - Toll-like receptor 4 signaling inhibits malignant pleural effusion by altering
      Th1/Th17 responses.
AB  - Toll-like receptor 4 (TLR4) is involved in multiple malignancies; however, the
      role of TLR4 in the pathogenesis of malignant pleural effusion (MPE) remains
      unknown. The objectives of this study were to explore the impact of TLR4
      signaling on the development of MPE in a murine model and to define the underline
      mechanisms by which TLR works. Development of MPE as well as proliferation and
      angiogenesis of pleural tumor were determined in TLR4(-/-) and wild type mice.
      Differentiation of Th1 and Th17 cells as well as their signal transductions was
      explored. The effects of TLR4 signaling on survival of mice bearing MPE were also
      investigated. Compared with wild type mice, Th1 cells were augmented, and Th17
      cells were suppressed in MPE from TLR4(-/-) mice. The in vitro experiments showed
      that TLR4 deficiency promoted Th1 cell differentiation via enhancing STAT1
      pathway and inhibited Th17 cell differentiation via suppressing STAT3 pathway.
      TLR4 deficiency promoted MPE formation and, thus, accelerated the death of mice
      bearing MPE, whereas intraperitoneal injection of anti-IFN-gamma mAb or
      recombinant mouse IL-17 protein into TLR4(-/-) mice was associated with improved
      survival. Our data provides the first definitive evidence of a role for TLR4
      signaling in protective immunity in the development of MPE. Our findings also
      demonstrate that TLR4 deficiency promotes MPE formation and accelerates mouse
      death by enhancing Th1 and suppressing Th17 response. 

PMID- 25939741
TI  - Paediatric resuscitation: Always breathe carefully.

PMID- 25939742
TI  - Laparoscopic suturing learning curve in an open versus closed box trainer.
AB  - BACKGROUND: The aim of this study was to examine the influence of training under
      direct vision prior to training with indirect vision on the learning curve of the
      laparoscopic suture task. METHODS: Novices were randomized in two groups. Group 1
      performed three suturing tasks in a transparent laparoscopic box trainer under
      direct vision followed by three suturing tasks in a standard non-transparent
      laparoscopic box trainer equipped with a 0 degrees  laparoscope. Group 2
      performed six suturing tasks in a standard laparoscopic box trainer. Performance
      time, motion analysis parameters (economy of movements) and interaction force
      parameters (tissue handling) were measured. Participants completed a
      questionnaire assessing: self-perceived dexterity before and after the training,
      their experienced frustration and the difficulty of the training. RESULTS: A
      total of 34 participants were included, one was excluded because of incomplete
      training. Group 1 used significantly less time to complete the total of six tasks
      (27 %). At the end of the training, there were no differences in motion or force
      parameters between the two groups. Group 2 rated their self-perceived dexterity
      after the training significantly lower than before the training and also reported
      significantly higher levels of frustration compared to group 1. Both groups rated
      the difficulty of the training similar. CONCLUSION: Novices benefit from starting
      their training of difficult basic laparoscopic skills, e.g., suturing, in a
      transparent box trainer without camera. It takes less time to complete the tasks,
      and they get less frustrated by the training with the same results on their
      economy of movements and tissue handling skills.

PMID- 25939743
TI  - Erratum to: Comparison of laparoscopic versus open left-sided hepatectomy for
      intrahepatic duct stones.

PMID- 25939744
TI  - An update on clinical applications of electrospun nanofibers for skin
      bioengineering.
AB  - Mimicking morphological similarities of the natural extra cellular matrix (ECM),
      described by ultrafine continuous fibers, high surface to volume ratio, and high
      porosity is valuable for effective regeneration of injured skin tissue.
      Electrospun nanofibers, being one of the most favorable and fast developing
      products of technology today, display a tremendous potential in wound healing and
      skin tissue engineering. Under the remarkable attention being given to
      electrospun nanofibrous scaffolds in promoting wound healing and skin
      regeneration, this review focuses on the potential of the electrospinning
      technique as a promising tool for constructing polymeric nanofibrous scaffolds
      with the favorable physicochemical properties needed for skin bioengineering. In
      addition, current applications of electrospun nanofibrous matrices for skin
      bioengineering are detailed in this review. 

PMID- 25939745
TI  - The protective effect of polymerized porcine hemoglobin (pPolyHb) on transient
      focal cerebral ischemia/reperfusion injury.
AB  - Glutaraldehyde-polymerized porcine hemoglobin (pPolyHb) is a hemoglobin-based
      oxygen carrier currently being developed as a potential red blood cell
      substitute. We assessed the protective effect of pPolyHb on transient focal
      cerebral ischemia/reperfusion (I/R) injury. Several outcomes were tested,
      including infarct size, neurological score, production of inflammatory factors,
      and markers of oxidative status. Our results show that pPolyHb can not only
      significantly reduce infarct volume and improve neurological score, but can also
      inhibit the expression of TNF-alpha and IL-1beta. Furthermore, the generation of
      MDA and MPO was reduced by pPolyHb. We conclude that pPolyHb has a positive
      effect on transient focal cerebral I/R injury. 

PMID- 25939748
TI  - Dynamic laryngeal narrowing in COPD may have effects on the trachea. Response.

PMID- 25939747
TI  - Two polar residues within C-terminal domain of M1 are critical for the formation
      of influenza A Virions.
AB  - The matrix protein 1 (M1) is the most abundant structural protein in influenza A
      virus particles. It oligomerizes to form the matrix layer under the lipid
      membrane, sustaining stabilization of the morphology of the virion. The present
      study indicates that M1 forms oligomers based on a fourfold symmetrical
      oligomerization pattern. Further analysis revealed that the oligomerization
      pattern of M1 was controlled by a highly conserved region within the C-terminal
      domain. Two polar residues of this region, serine-183 (S183) and threonine-185
      (T185), were identified to be critical for the oligomerization pattern of M1. M1
      point mutants suggest that single S183A or T185A substitution could result in the
      production of morphologically filamentous particles, while double substitutions,
      M1-S183A/T185A, totally disrupted the fourfold symmetry and resulted in the
      failure of virus production. These data indicate that the polar groups in these
      residues are essential to control the oligomerization pattern of M1. Thus, the
      present study will aid in determining the mechanisms of influenza A virus matrix
      layer formation during virus morphogenesis. 

PMID- 25939749
TI  - Anti-inflammatory effects of PGE2 in the lung: role of the EP4 receptor subtype.
AB  - BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are chronic
      inflammatory diseases of the airway. Current treatment options (long acting beta
      adrenoceptor agonists and glucocorticosteroids) are not optimal as they are only
      effective in certain patient groups and safety concerns exist regarding both
      compound classes. Therefore, novel bronchodilator and anti-inflammatory
      strategies are being pursued. Prostaglandin E2 (PGE2) is an arachidonic acid
      derived eicosanoid produced by the lung which acts on four different G-protein
      coupled receptors (EP1-4) to cause an array of beneficial and deleterious
      effects. The aim of this study was to identify the EP receptor mediating the anti
      inflammatory actions of PGE2 in the lung using a range of cell-based assays and
      in vivo models. METHODS AND RESULTS: It was demonstrated in three distinct model
      systems (innate stimulus, lipopolysaccharide (LPS); allergic response, ovalbumin
      (OVA); inhaled pollutant, cigarette smoke) that mice missing functional EP4
      (Ptger4(-/-)) receptors had higher levels of airway inflammation, suggesting that
      endogenous PGE2 was suppressing inflammation via EP4 receptor activation. Cell
      based assay systems (murine and human monocytes/alveolar macrophages)
      demonstrated that PGE2 inhibited cytokine release from LPS-stimulated cells and
      that this was mimicked by an EP4 (but not EP1-3) receptor agonist and inhibited
      by an EP4 receptor antagonist. The anti-inflammatory effect occurred at the
      transcriptional level and was via the adenylyl cyclase/cAMP/ cAMP-dependent
      protein kinase (PKA) axis. CONCLUSION: This study demonstrates that EP4 receptor
      activation is responsible for the anti-inflammatory activity of PGE2 in a range
      of disease relevant models and, as such, could represent a novel therapeutic
      target for chronic airway inflammatory conditions.

PMID- 25939750
TI  - Umbellate distortions of the uranyl coordination environment result in a stable
      and porous polycatenated framework that can effectively remove cesium from
      aqueous solutions.
AB  - Searching for new chemically durable and radiation-resistant absorbent materials
      for actinides and their fission products generated in the nuclear fuel cycle
      remain highly desirable, for both waste management and contamination remediation.
      Here we present a rare case of 3D uranyl organic framework material built through
      polycatenating of three sets of graphene-like layers, which exhibits significant
      umbellate distortions in the uranyl equatorial planes studied thoroughly by
      linear transit calculations. This unique structural arrangement leads to high
      beta and gamma radiation-resistance and chemical stability in aqueous solutions
      within a wide pH range from 3 to 12. Being equipped with the highest surface area
      among all actinide compounds known to date and completely exchangeable
      [(CH3)2NH2](+) cations in the structure, this material is able to selectively
      remove cesium from aqueous solutions while retaining the polycatenated framework
      structure. 

PMID- 25939751
TI  - Dimethyl fumarate and the oleanane triterpenoids, CDDO-imidazolide and CDDO
      methyl ester, both activate the Nrf2 pathway but have opposite effects in the A/J
      model of lung carcinogenesis.
AB  - Lung cancer accounts for the highest number of cancer-related deaths in the USA,
      highlighting the need for better prevention and therapy. Activation of the Nrf2
      pathway detoxifies harmful insults and reduces oxidative stress, thus preventing
      carcinogenesis in various preclinical models. However, constitutive activation of
      the Nrf2 pathway has been detected in numerous cancers, which confers a survival
      advantage to tumor cells and a poor prognosis. In our study, we compared the
      effects of two clinically relevant classes of Nrf2 activators, dimethyl fumarate
      (DMF) and the synthetic oleanane triterpenoids, CDDO-imidazolide (CDDO-Im) and
      CDDO-methyl ester (CDDO-Me) in RAW 264.7 mouse macrophage-like cells, in VC1 lung
      cancer cells and in the A/J model of lung cancer. Although the triterpenoids and
      DMF both activated the Nrf2 pathway, CDDO-Im and CDDO-Me were markedly more
      potent than DMF. All of these drugs reduced the production of reactive oxygen
      species and inhibited nitric oxide production in RAW264.7 cells, but the
      triterpenoids were 100 times more potent than DMF in these assays. Microarray
      analysis revealed that only 52 of 99 Nrf2-target genes were induced by all three
      compounds, and each drug regulated a unique subset of Nrf2 genes. These drugs
      also altered the expression of other genes important in lung cancer independent
      of Nrf2. Although all three compounds enhanced the phosphorylation of CREB, only
      DMF increased the phosphorylation of Akt. CDDO-Me, at either 12.5 or 50mg/kg of
      diet, was the most effective drug in our lung cancer mouse model. Specifically,
      CDDO-Me significantly reduced the average tumor number, size and burden compared
      with the control group (P < 0.05). Additionally, 52% of the tumors in the control
      group were high-grade tumors compared with only 14% in the CDDO-Me group. Though
      less potent, CDDO-Im had similar activity as CDDO-Me. In contrast, 61-63% of the
      tumors in the DMF groups (400-1200mg/kg diet) were high-grade tumors compared
      with 52% for the controls (P < 0.05). Additionally, DMF significantly increased
      the average number of tumors compared with the controls (P < 0.05). Thus, in
      contrast to the triterpenoids, which effectively reduced pathogenesis in A/J
      mice, DMF enhanced the severity of lung carcinogenesis in these mice.
      Collectively, these results suggest that although CDDO-Im, CDDO-Me and DMF all
      activate the Nrf2 pathway, they target distinct genes and signaling pathways,
      resulting in opposite effects for the prevention of experimental lung cancer.

PMID- 25939752
TI  - Reducing DNA methylation suppresses colon carcinogenesis by inducing tumor cell
      differentiation.
AB  - The forced reduction of global DNA methylation suppresses tumor development in
      several cancer models in vivo. Nevertheless, the mechanisms underlying these
      suppressive effects remain unclear. In this report, we describe our findings
      showing that a genome-wide reduction in the DNA methylation levels induces
      cellular differentiation in association with decreased cell proliferation in Apc
      (Min/+) mouse colon tumor cells in vivo. Colon tumor-specific DNA methylation at
      Cdx1 is reduced in the DNA-hypomethylated tumors accompanied by Cdx1 derepression
      and an increased expression of intestinal differentiation-related genes.
      Furthermore, a histological analysis revealed that Cdx1 derepression in the DNA
      hypomethylated tumors is correlated with the differentiation of colon tumor
      cells. Similarly, the treatment of human colon cancer cell lines with a
      hypomethylating agent induces differentiation-related genes, including CDX1. We
      herein propose that DNA demethylation exerts a tumor suppressive effect in the
      colon by inducing tumor cell differentiation.

PMID- 25939753
TI  - Bmi1 is required for the initiation of pancreatic cancer through an Ink4a
      independent mechanism.
AB  - Epigenetic dysregulation is involved in the initiation and progression of many
      epithelial cancers. BMI1, a component of the polycomb protein family, plays a key
      role in these processes by controlling the histone ubiquitination and long-term
      repression of multiple genomic loci. BMI1 has previously been implicated in
      pancreatic homeostasis and the function of pancreatic cancer stem cells. However,
      no work has yet addressed its role in the early stages of pancreatic cancer
      development. Here, we show that BMI1 is required for the initiation of murine
      pancreatic neoplasia using a novel conditional knockout of Bmi1 in combination
      with a Kras(G12D)-driven pancreatic cancer mouse model. We also demonstrate that
      the requirement for Bmi1 in pancreatic carcinogenesis is independent of the
      Ink4a/Arf locus and at least partially mediated by dysregulation of reactive
      oxygen species. Our data provide new evidence of the importance of this
      epigenetic regulator in the genesis of pancreatic cancer.

PMID- 25939754
TI  - Adolescent Risk for Intimate Partner Violence Perpetration.
AB  - The prevention of intimate partner violence is a desirable individual and public
      health goal for society. The purpose of this study is to provide a comprehensive
      assessment of adolescent risk factors for partner violence in order to inform the
      development of evidence-based prevention strategies. We utilize data from the
      Rochester Youth Development Study, a two decade long prospective study of a
      representative community sample of 1000 participants that has extensive measures
      of adolescent characteristics, contexts, and behaviors that are potential
      precursors of partner violence. Using a developmental psychopathology framework,
      we assess self-reported partner violence perpetration in emerging adulthood (ages
      20-22) and in adulthood (ages 29-30) utilizing the Conflict Tactics Scale. Our
      results indicate that risk factors for intimate partner violence span several
      developmental domains and are substantially similar for both genders.
      Internalizing and externalizing problem behaviors as well as early intimate
      relationships are especially salient for both genders. Additionally, cumulative
      risk across a number of developmental domains places adolescents at particularly
      high risk of perpetrating partner violence. Implications for prevention include
      extending existing prevention programs that focus on high risk groups with
      multiple risks for developmental disruption, as well as focusing on preventing or
      mitigating identified risk factors across both genders.

PMID- 25939755
TI  - Seasonal demography of a cyclic lemming population in the Canadian Arctic.
AB  - 1. The causes of cyclical fluctuations in animal populations remain a
      controversial topic in ecology. Food limitation and predation are two leading
      hypotheses to explain small mammal population dynamics in northern environments.
      We documented the seasonal timing of the decline phases and demographic
      parameters (survival and reproduction) associated with population changes in
      lemmings, allowing us to evaluate some predictions from these two hypotheses. 2.
      We studied the demography of brown lemmings (Lemmus trimucronatus), a species
      showing 3- to 4-year population cycles in the Canadian Arctic, by combining
      capture-mark-recapture analysis of summer live-trapping with monitoring of winter
      nests over a 10-year period. We also examined the effects of some weather
      variables on survival. 3. We found that population declines after a peak occurred
      between the summer and winter period and not during the winter. During the
      summer, population growth was driven by change in survival, but not in fecundity
      or proportion of juveniles, whereas in winter population growth was driven by
      changes in late summer and winter reproduction. 4. We did not find evidence for
      direct density dependence on summer demographic parameters, though our analysis
      was constrained by the paucity of data during the low phase. Body mass, however,
      was highest in peak years. 5. Weather effects were detected only in early summer
      when lemming survival was positively related to snow depth at the onset of melt
      but negatively related to rainfall. 6. Our results show that high mortality
      causes population declines of lemmings during summer and fall, which suggests
      that predation is sufficient to cause population crashes, whereas high winter
      fecundity is the primary factor leading to population irruptions. The positive
      association between snow depth and early summer survival may be due to the
      protective cover offered by snow against predators. It is still unclear why
      reproduction remains low during the low phase.

PMID- 25939756
TI  - Job satisfaction and horizontal violence in hospital staff registered nurses: the
      mediating role of peer relationships.
AB  - AIMS AND OBJECTIVES: To describe the association between horizontal violence and
      job satisfaction in hospital staff registered nurses and the degree to which peer
      relationships mediates the relationship. Additionally, the association between
      nurse and work characteristics and job satisfaction were determined. BACKGROUND:
      Horizontal violence is a major predictor of nurses' job satisfaction. Yet, not
      enough is known about the relationship between these variables. Job satisfaction
      is an important variable to study because it is a predictor of patient care
      quality and safety internationally. Peer relationships, a job satisfier for
      nurses, was identified as a potential mediator in the association between
      horizontal violence and job satisfaction. DESIGN: Cross-sectional mediational
      model testing. METHODS: An anonymous four-part survey of a random sample of 175
      hospital staff registered nurses working in California provided the data. Data
      about horizontal violence, peer relationships, job satisfaction, and nurse and
      work characteristics were collected between March-August 2010. RESULTS: A
      statistically significant negative relationship was found between horizontal
      violence and peer relationships, job satisfaction and a statistically significant
      positive relationship was found between peer relationships and job satisfaction.
      Peer relationships mediated the association between horizontal violence and job
      satisfaction. Job satisfaction was reported as higher by nurses who worked in
      teaching hospitals. There were no statistically significant differences in job
      satisfaction based on gender, ethnicity, basic registered nurse education,
      highest degree held, size of hospital or clinical area. CONCLUSIONS: The results
      suggest that peer relationships can attenuate the negative relationship between
      horizontal violence and job satisfaction. This adds to the extant literature on
      the relationship between horizontal violence and job satisfaction. RELEVANCE TO
      CLINICAL PRACTICE: The findings highlight peer relationships as an important
      factor when considering effective interventions that foster hospital staff
      registered nurses' job satisfaction in the presence of horizontal violence.

PMID- 25939757
TI  - New Insights from Major Prospective Cohort Studies with Cardiovascular Magnetic
      Resonance (CMR).
AB  - Since 1948, epidemiology studies played an important role in understanding
      cardiovascular disease and afforded an opportunity to learn about newer
      diagnostic tests. In 2000, the MESA Study incorporated several advanced
      cardiovascular imaging modalities including cardiac magnetic resonance imaging
      (MRI) and coronary artery calcium scans. The decade of follow-up enabled
      prognosis studies, an important step beyond association studies. In brief, left
      ventricular hypertrophy by cardiac MRI predicted incident heart failure and
      stroke. In the MESA Study, coronary artery calcium was a better predictor of
      coronary artery disease end points than the non-contrast-enhanced MRI scan. In
      the ICELAND MI substudy of the AGES-Reykjavik Study, a contrast-enhanced MRI scan
      detected many more unrecognized myocardial infarctions (MIs) (UMIs) than detected
      by electrocardiography and documented these UMI had adverse prognostic
      significance. Thus, cardiac MRI has been successfully incorporated into large
      population studies and shown added value over conventional measurements of
      cardiovascular disease. 

PMID- 25939758
TI  - A comparison of food habits and prey preference of Amur tiger (Panthera tigris
      altaica) at three sites in the Russian Far East.
AB  - Prey availability is one of the principal drivers of tiger distribution and
      abundance. Therefore, formulating effective conservation strategies requires a
      clear understanding of tiger diet. We used scat analysis in combination with data
      on the abundance of several prey species to estimate Amur tiger diet and
      preference at 3 sites in the Russian Far East. We also examined the effect of
      pseudoreplication on estimates of tiger diet. We collected 770 scats across the 3
      sites. Similar to previous studies, we found that tigers primarily preyed on
      medium to large ungulates, with wild boar, roe, sika and red deer collectively
      comprising 86.7% of total biomass consumed on average. According to Jacobs'
      index, tigers preferred wild boar, and avoided sika deer. Variation in preference
      indices derived from these scat analyses compared to indices derived from kill
      data appear to be due to adjustments in biomass intake when sex-age of a killed
      individual is known: a component missing from scat data. Pseudoreplication
      (multiple samples collected from a single kill site) also skewed results derived
      from scat analyses. Scat analysis still appears useful in providing insight into
      the diets of carnivores when the full spectrum of prey species needs to be
      identified, or when sample sizes from kill data are not sufficient. When sample
      sizes of kill data are large (as is now possible with GPS-collared animals), kill
      data adjusted by sex-age categories probably provides the most accurate estimates
      of prey biomass composition. Our results provide further confirmation of the
      centrality of medium ungulates, in particular wild boar, to Amur tiger diet, and
      suggest that the protection of this group of species is critical to Amur tiger
      conservation. 

PMID- 25939759
TI  - Contrasting patterns of care for musculoskeletal disorders and injuries of the
      upper extremity and knee through workers' compensation and private health care
      insurance among union carpenters in Washington State, 1989 to 2008.
AB  - BACKGROUND: Musculoskeletal symptoms and disorders (MSDIs) are common reasons for
      visits to medical providers in the general population and they are common work
      related complaints. Prior reports raise concerns as to whether declines in
      workers' compensation (WC) rates represent true improvement in occupational
      health and safety or shifting of care to other payment systems. METHODS: By
      linking administrative records, we compared patterns of WC claims and private
      health care utilization for disorders of the upper extremity (UE) and knee among
      a large cohort of union carpenters over a 20-year period. RESULTS: As WC claim
      rates declined, private health care utilization increased. The increase was muted
      somewhat but sustained when adjusting for other patterns of health care
      utilization. CONCLUSIONS: Findings suggest the decline of WC claim rates do not
      solely represent improved occupational safety in this population, but also a
      considerable shifting of care to their private insurance coverage over time.

PMID- 25939760
TI  - MEK Inhibition Overcomes Cisplatin Resistance Conferred by SOS/MAPK Pathway
      Activation in Squamous Cell Carcinoma.
AB  - Genomic analyses of squamous cell carcinoma (SCC) have yet to yield significant
      strategies against pathway activation to improve treatment. Platinum-based
      chemotherapy remains the mainstay of treatment for SCC of different histotypes
      either as a single-agent or alongside other chemotherapeutic drugs or
      radiotherapy; however, resistance inevitably emerges, which limits the duration
      of treatment response. To elucidate mechanisms that mediate resistance to
      cisplatin, we compared drug-induced perturbations to gene and protein expression
      between cisplatin-sensitive and -resistant SCC cells, and identified MAPK-ERK
      pathway upregulation and activation in drug-resistant cells. ERK-induced
      resistance appeared to be activated by Son of Sevenless (SOS) upstream, and
      mediated through Bim degradation downstream. Clinically, elevated p-ERK
      expression was associated with shorter disease-free survival in patients with
      locally advanced head and neck SCC treated with concurrent chemoradiation.
      Inhibition of MEK/ERK, but not that of EGFR or RAF, augmented cisplatin
      sensitivity in vitro and demonstrated efficacy and tolerability in vivo.
      Collectively, these findings suggest that inhibition of the activated SOS-MAPK
      ERK pathway may augment patient responses to cisplatin treatment.

PMID- 25939761
TI  - Preclinical Test of Dacomitinib, an Irreversible EGFR Inhibitor, Confirms Its
      Effectiveness for Glioblastoma.
AB  - Glioblastomas (GBM) are devastating tumors in which there has been little
      clinical improvement in the last decades. New molecularly directed therapies are
      under development. EGFR is one of the most promising targets, as this receptor is
      mutated and/or overexpressed in nearly half of the GBMs. However, the results
      obtained with first-generation tyrosine-kinase inhibitors have been disappointing
      with no clear predictive markers of tumor response. Here, we have tested the
      antitumoral efficacy of a second-generation inhibitor, dacomitinib (PF299804,
      Pfizer), that binds in an irreversible way to the receptor. Our results confirm
      that dacomitinib has an effect on cell viability, self-renewal, and proliferation
      in EGFR-amplified +/- EGFRvIII GBM cells. Moreover, systemic administration of
      dacomitinib strongly impaired the in vivo tumor growth rate of these EGFR
      amplified cell lines, with a decrease in the expression of stem cell-related
      markers. However, continuous administration of the compound was required to
      maintain the antitumor effect. The data presented here confirm that dacomitinib
      clearly affects receptor signaling in vivo and that its strong antitumoral effect
      is independent of the presence of mutant receptor isoforms although it could be
      affected by the PTEN status (as it is less effective in a PTEN-deleted GBM line).
      Dacomitinib is being tested in second line for EGFR-amplified GBMs. We hope that
      our results could help to select retrospectively molecular determinants of this
      response and to implement future trials with dacomitinib (alone or in combination
      with other inhibitors) in newly diagnosed GBMs.

PMID- 25939763
TI  - Emergency measures: Adaptive response to pathogen intrusion in the ant nest.
AB  - Ants have developed prophylactic and hygienic behaviours in order to limit risks
      of pathogenic outbreaks inside their nest, which are often called social
      immunity. Here, we test whether ants can adapt the "social immune response" to
      the level of pathogenic risk in the colony. We challenged Myrmica rubra colonies
      with dead nestmates that had either died from being frozen or from infection by
      the fungus Metarhizium anisopliae. Ant survival was compromised by the presence
      of the fungus-bearing corpses: workers died faster with a significantly lower
      survival from the 4th day compared to workers challenged with freeze-killed
      corpses. When faced with fungus-bearing corpses, workers responded quickly by
      increasing hygienic behaviours: they spent more time cleaning the nest, moving
      the corpses, and self-grooming. Ants in fungus-threatened colonies also decreased
      contact rates with other workers, and moved corpses further in the corners of the
      nest than in colonies in contact with non-infected corpses. These results show
      that ant colonies are able to assess the risk level associated with the presence
      of corpses in the nest, and adjust their investment in terms of hygienic
      behaviour. 

PMID- 25939762
TI  - Protein Phosphatase 2A Inhibition with LB100 Enhances Radiation-Induced Mitotic
      Catastrophe and Tumor Growth Delay in Glioblastoma.
AB  - Protein phosphatase 2A (PP2A) is a tumor suppressor whose function is lost in
      many cancers. An emerging, though counterintuitive, therapeutic approach is
      inhibition of PP2A to drive damaged cells through the cell cycle, sensitizing
      them to radiotherapy. We investigated the effects of PP2A inhibition on U251
      glioblastoma cells following radiation treatment in vitro and in a xenograft
      mouse model in vivo. Radiotherapy alone augmented PP2A activity, though this was
      significantly attenuated with combination LB100 treatment. LB100 treatment
      yielded a radiation dose enhancement factor of 1.45 and increased the rate of
      postradiation mitotic catastrophe at 72 and 96 hours. Glioblastoma cells treated
      with combination LB100 and radiotherapy maintained increased gamma-H2AX
      expression at 24 hours, diminishing cellular repair of radiation-induced DNA
      double-strand breaks. Combination therapy significantly enhanced tumor growth
      delay and mouse survival and decreased p53 expression 3.68-fold, compared with
      radiotherapy alone. LB100 treatment effectively inhibited PP2A activity and
      enhanced U251 glioblastoma radiosensitivity in vitro and in vivo. Combination
      treatment with LB100 and radiation significantly delayed tumor growth, prolonging
      survival. The mechanism of radiosensitization appears to be related to increased
      mitotic catastrophe, decreased capacity for repair of DNA double-strand breaks,
      and diminished p53 DNA-damage response pathway activity.

PMID- 25939764
TI  - Graphene oxide-mediated electrochemistry of glucose oxidase on glassy carbon
      electrodes.
AB  - Glucose oxidase (GOD) was immobilized on glassy carbon electrodes in the presence
      of graphene oxide (GO) as a model system for the interaction between GO and
      biological molecules. Lyotropic properties of didodecyldimethylammonium bromide
      (DDAB) were used to stabilize the enzymatic layer on the electrode surface
      resulting in a markedly improved electrochemical response of the immobilized GOD.
      Transmission electron microscopy images of the GO with DDAB confirmed the
      distribution of the GO in a two-dimensional manner as a foil-like material.
      Although it is known that glassy carbon surfaces are not ideal for hydrogen
      peroxide detection, successful chronoamperometric titrations of the GOD in the
      presence of GO with beta-d-glucose were performed on glassy carbon electrodes,
      whereas no current response was detected upon beta-d-glucose addition in the
      absence of GO. The GOD-DDAB-GO system displayed a high turnover efficiency and
      substrate affinity as a glucose biosensor. The simplicity and ease of the
      electrode preparation procedure of this GO/DDAB system make it a good candidate
      for immobilizing other biomolecules for fabrication of amperometric biosensors. 

PMID- 25939765
TI  - Nanostructured cavity devices for extracellular stimulation of HL-1 cells.
AB  - Microelectrode arrays (MEAs) are state-of-the-art devices for extracellular
      recording and stimulation on biological tissue. Furthermore, they are a relevant
      tool for the development of biomedical applications like retina, cochlear and
      motor prostheses, cardiac pacemakers and drug screening. Hence, research on
      functional cell-sensor interfaces, as well as the development of new surface
      structures and modifications for improved electrode characteristics, is a vivid
      and well established field. However, combining single-cell resolution with
      sufficient signal coupling remains challenging due to poor cell-electrode
      sealing. Furthermore, electrodes with diameters below 20 um often suffer from a
      high electrical impedance affecting the noise during voltage recordings. In this
      study, we report on a nanocavity sensor array for voltage-controlled stimulation
      and extracellular action potential recordings on cellular networks. Nanocavity
      devices combine the advantages of low-impedance electrodes with small cell-chip
      interfaces, preserving a high spatial resolution for recording and stimulation. A
      reservoir between opening aperture and electrode is provided, allowing the cell
      to access the structure for a tight cell-sensor sealing. We present the well
      controlled fabrication process and the effect of cavity formation and electrode
      patterning on the sensor's impedance. Further, we demonstrate reliable voltage
      controlled stimulation using nanostructured cavity devices by capturing the
      pacemaker of an HL-1 cell network. 

PMID- 25939766
TI  - Promoting mental health of very young children.

PMID- 25939767
TI  - The Effect of Sperm Concentration and Storage Vessel on Quercetin-Supplemented
      Rabbit Semen During Chilled Storage.
AB  - Extending the shelf life of chilled rabbit spermatozoa is vital for the expansion
      of the farmed rabbit industry. This study evaluated the relationship between
      sperm concentration and packaging on in vitro quality of chilled rabbit semen
      over 96 h. Semen was collected from adult bucks (n = 4) and pooled at 37 degrees
      C following evaluation. Pooled ejaculates were diluted with a Tris-based extender
      supplemented with 100 MUm quercetin to a concentration of 15, 30 or 60 * 10(6) 
      spermatozoa/ml, packaged into plastic tubes or 0.5-ml straws and stored at 15
      degrees C. Sperm quality was assessed by computer-assisted sperm Analysis [total
      motility (tMOT)] and flow cytometry [viability, acrosome integrity, H2 O2
      production, plasma membrane disorder, apoptosis and DNA fragmentation index
      (DFI)] at 0, 48, 72 and 96 h. From 48 h, concentrations of 30 and 60 * 10(6) 
      spermatozoa/ml reported the highest tMOT, irrespective of storage vessel (p <
      0.05). Storage in straws reduced oxidative stress and improved plasma membrane
      stability. The %DFI, mean DFI and SD-DFI were increased in spermatozoa stored in
      tubes compared with straws (p < 0.05). Although the use of low sperm
      concentrations in artificial insemination doses would facilitate greater
      dispersion of genetically superior rabbit bucks, dilution to 15 * 10(6) 
      spermatozoa/ml had a detrimental impact on motility. As such, chilled storage at
      30 * 10(6)  spermatozoa/ml may provide a suitable balance between motility and H2
      O2 production to best maintain overall sperm function and should be evaluated in
      a large-scale AI trial. 

PMID- 25939768
TI  - E-selectin expression induced by Porphyromonas gingivalis in human endothelial
      cells via nucleotide-binding oligomerization domain-like receptors and Toll-like
      receptors.
AB  - Porphyromonas gingivalis, an important periodontal pathogen, has been proved to
      actively invade cells, induce endothelial cell activation, and promote
      development of atherosclerosis. Innate immune surveillance, which includes the
      activity of nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs)
      and Toll-like receptors (TLRs), are essential for the control of microbial
      infections; however, the roles of receptor families in P. gingivalis infections
      remain unclear. Here, we examined the roles of NLRs and TLRs in endothelial cell
      activation caused by P. gingivalis. Live P. gingivalis and whole cell sonicates
      were used to stimulate endothelial cells, and both showed upregulation of E
      selectin as well as NOD1, NOD2, and TLR2. In addition, silencing of these genes
      in endothelial cells infected with P. gingivalis led to a reduction in E-selectin
      expression. Porphyromonas gingivalis also induced nuclear factor-kappaB (NF
      kappaB) and P38 mitogen-activated protein kinase (MAPK) activity in endothelial
      cells, whereas small interfering RNA targeting NOD1 significantly reduced these
      signals. Moreover, inhibition of either NOD2 or TLR2 inhibited NF-kappaB
      significantly, but had only a weak inhibitory effect on P38 MAPK signaling.
      Direct inhibition of NF-kappaB and P38 MAPK significantly attenuated E-selectin
      expression induced by P. gingivalis in endothelial cells. Taken together, these
      findings suggest that NOD1, NOD2, and TLR2 play important, non-redundant roles in
      endothelial cell activation following P. gingivalis infection.

PMID- 25939770
TI  - The burden of care: a focus group study of healthcare practitioners in Scotland
      talking about parental drug misuse.
AB  - Parenting and family support are key prevention and intervention strategies for
      improving outcomes for children and families affected by parental drug misuse.
      However, little is known about the delivery of parenting support for drug
      dependent parents, particularly within universal healthcare services. This study
      aimed to explore the way healthcare practitioners engage with this challenging
      agenda. Four multidisciplinary focus groups involving a purposive sample of 18
      experienced healthcare professionals were conducted in Scotland. Participants
      included general practitioners, midwives, public health nurses and addiction
      staff who work together to provide care for vulnerable families. A focus group
      topic guide was developed to explore the views and experiences of these
      healthcare professionals in relation to providing parenting support for drug
      using parents, predominantly those receiving opioid substitution therapy. Data
      were analysed using a constant comparison method and thematic approach. The
      overarching narrative which united the focus group discussions was about the
      'burden of care' that these families pose for frontline healthcare professionals.
      Recurring themes centred on three key issues: the problematic nature of drug
      using parents themselves; clinical challenges in living up to the ideals of
      professional practice; and the wider context in which current practice is
      governed. Professionals expressed ambivalence over their parenting support role;
      anxiety over responsibility for intervening with this 'hard-to-engage'
      population; and concern over 'dwindling' resources and lack of organisational
      support. Nevertheless, strategies and opportunities for providing parenting
      support were acknowledged and there was consensus about the need for further
      skills training. Despite a proliferation of policy and good practice guidance on
      the delivery of parenting support for drug-dependent parents, the findings of
      this study suggest that significant challenges remain. Notably, our findings
      raise questions about whose role it is to provide parenting support to drug-using
      mothers and fathers, especially those who are not involved in the child
      protection system.

PMID- 25939769
TI  - Inhibition of colony stimulating factor-1 receptor improves antitumor efficacy of
      BRAF inhibition.
AB  - BACKGROUND: Malignant melanoma is an aggressive tumor type that often develops
      drug resistance to targeted therapeutics. The production of colony stimulating
      factor 1 (CSF-1) in tumors recruits myeloid cells such as M2-polarized
      macrophages and myeloid derived suppressor cells (MDSC), leading to an immune
      suppressive tumor milieu. METHODS: We used the syngeneic mouse model of BRAF
      (V600E) -driven melanoma SM1, which secretes CSF-1, to evaluate the ability of
      the CSF-1 receptor (CSF-1R) inhibitor PLX3397 to improve the antitumor efficacy
      of the oncogenic BRAF inhibitor vemurafenib. RESULTS: Combined BRAF and CSF-1R
      inhibition resulted in superior antitumor responses compared with either therapy
      alone. In mice receiving PLX3397 treatment, a dramatic reduction of tumor
      infiltrating myeloid cells (TIM) was observed. In this model, we could not detect
      a direct effect of TIMs or pro-survival cytokines produced by TIMs that could
      confer resistance to PLX4032 (vemurafenib). However, the macrophage inhibitory
      effects of PLX3397 treatment in combination with the paradoxical activation of
      wild type BRAF-expressing immune cells mediated by PLX4032 resulted in more tumor
      infiltrating lymphocytes (TIL). Depletion of CD8+ T-cells abrogated the antitumor
      response to the combination therapy. Furthermore, TILs isolated from SM1 tumors
      treated with PLX3397 and PLX4032 displayed higher immune potentiating activity.
      CONCLUSIONS: The combination of BRAF-targeted therapy with CSF-1R blockade
      resulted in increased CD8 T-cell responses in the SM1 melanoma model, supporting
      the ongoing evaluation of this therapeutic combination in patients with BRAF
      (V600) mutant metastatic melanoma.

PMID- 25939771
TI  - The influence of childhood asthma on puberty and height in Swedish adolescents.
AB  - BACKGROUND: Evidence relating to the effect of asthma on puberty or height is
      inconclusive. We aimed to examine whether the exposure of childhood asthma,
      including timing and phenotypes, and inhaled corticosteroid (ICS) use is either
      cross-sectionally or longitudinally associated with the outcomes of pubertal
      staging or height. METHODS: This study employed data from a longitudinal,
      population-based cohort of Swedish children (born 1994-1996). At ages 1, 2, 4, 8,
      and 12 years, parent-reported data on asthma and ICS use in the previous 12
      months were collected. At 8 and 12 years, height was ascertained at a clinical
      visit, and child-reported, respectively. At 12 years, children answered puberty
      related questions. RESULTS: Retention through 12 years was 82% (3366/4089).
      Participants without puberty data (n = 620) were excluded, yielding a study
      population of 2746 (67%). Asthma at 8 years, including timing of onset and
      phenotypes, was not statistically significantly associated with pubertal staging
      in adjusted models. Children with asthma averaged 0.93 cm (95% CI 0.35-1.50)
      shorter than children without asthma. Children with asthma using ICS were 1.28
      (95% CI 0.62-1.95) shorter than those with asthma without using ICS. CONCLUSIONS:
      We found no consistent association between asthma and pubertal staging. Children
      with asthma were shorter than those without asthma. Moreover, children with
      asthma using ICS were shorter than those not using ICS.

PMID- 25939772
TI  - Surface coal mining influences on macroinvertebrate assemblages in streams of the
      Canadian Rocky Mountains.
AB  - To determine the region-specific impacts of surface coal mines on
      macroinvertebrate community health, chemical and physical stream characteristics
      and macroinvertebrate family and community metrics were measured in surface coal
      mine-affected and reference streams in the Canadian Rocky Mountains. Water
      chemistry was significantly altered in mine-affected streams, which had elevated
      conductivity, alkalinity, and selenium and ion concentrations compared with
      reference conditions. Multivariate redundancy analysis (RDA) indicated
      alterations in macroinvertebrate communities downstream of mine sites. In RDA
      ordination, Ephemeroptera family densities, family richness, Ephemeroptera,
      Plecoptera, Trichoptera (EPT) richness, and % Ephemeroptera declined, whereas
      densities of Capniidae stoneflies increased along environmental gradients defined
      by variables associated with mine influence including waterborne Se
      concentration, alkalinity, substrate embeddedness, and interstitial material
      size. Shifts in macroinvertebrate assemblages may have been the result of
      multiple region-specific stressors related to mining influences including
      selenium toxicity, ionic toxicity, or stream substrate modifications.

PMID- 25939773
TI  - Geometries, stabilities and fragmental channels of neutral and charged sulfur
      clusters: Sn(Q) (n = 3-20, Q = 0, +/-1).
AB  - We have performed unbiased searches for the global minimum structures of neutral
      and charged sulfur clusters Sn(Q) (n = 3-20, Q = 0, +/-1) relying on the CALYPSO
      structure searching method combined with density functional theory geometric
      optimization. Very accurate ab initio calculations are used to determine relative
      stabilities and energy ranking among competing low-lying isomers of the neutral
      and charged sulfur clusters obtained from the structure search. The harmonic
      vibrational analysis is also undertaken to assure that the optimized geometries
      are the true minima. It is shown that the most equilibrium geometries of sulfur
      clusters are closed three-dimensional (3D) helical rings, which is in agreement
      with the experimental observations. The binding energies, second-order energy
      differences, and highest occupied-lowest unoccupied molecular orbital (HOMO-LUMO)
      gaps of the considered species are calculated and analyzed systematically.
      Additionally, the fragmentation channels are determined and the results indicate
      that the Sn(Q) -> S2 + Sn-2(Q) channel is a route that the small clusters (n = 3
      10) favor, while the larger species (n = 13-20) prefer the Sn(Q) -> S8 + Sn-8(Q)
      channel. 

PMID- 25939775
TI  - Sorting out cirrhosis: mechanisms of non-response to hepatitis C therapy.
AB  - Although cirrhosis has long been recognized as an important negative predictor of
      treatment response for hepatitis C virus (HCV) therapy, the mechanisms underlying
      this association remain relatively poorly understood. Treatment has progressed
      rapidly with the introduction of highly effective all-oral therapies, with
      promising outcomes even in patients with advanced cirrhosis. However, even with
      the new therapies, it is clear that patients with cirrhosis require special
      attention. Efficacy continues to be somewhat reduced compared to non-cirrhotic
      patients and safety is an important concern. In this review, we explore the
      reasons for treatment non-response in patients with cirrhosis. We focus on how
      cirrhosis impacts on four important areas including drug delivery, drug uptake
      and metabolism, immune responses and drug toxicity with examples from the
      clinical and basic literature. Fortunately, as treatment continues to progress,
      many of the challenges of treating patients with cirrhosis will become less and
      less problematic. 

PMID- 25939774
TI  - Minimal residual disease detection in autologous stem cell grafts from patients
      with high risk neuroblastoma.
AB  - BACKGROUND: The clinical significance of minimal residual disease (MRD) detected
      by real-time quantitative PCR (qPCR) in autologous stem cell grafts in high risk
      neuroblastoma is still controversial. In this retrospective multicenter study,
      autologous stem cell grafts of a large cohort were studied using a panel of RNA
      markers. PROCEDURE: From 104 patients with high risk neuroblastoma, who received
      autologous stem cell transplantation as first line treatment, 66 peripheral blood
      stem cells (PBSC) and 38 CD34+ selected grafts were retrospectively collected at
      2 Dutch and 12 German centers between 1997 and 2010. To investigate graft
      contamination qPCR was performed by using 5 neuroblastoma specific markers
      (PHOX2B, TH, DDC, CHRNA3, and DBH). RESULTS: In PBSC 6/66 (9%) and in CD34+
      selected grafts 3/38 (8%) samples were contaminated. Graft contamination was not
      associated with an unfavorable outcome (5-years OS, 66% vs. 50.5%; P=0.6 and 5
      years EFS, 22% vs. 35%, P=0.7). In multivariate Cox analysis BM MRD at time of
      harvest was significantly associated with survival (P=0.008 OS and P=0.002 EFS),
      but graft contamination was still not associated with an unfavorable outcome
      (P=0.9 OS and P=1 EFS). CONCLUSIONS: Graft contamination is very infrequent in
      this retrospective cohort of patients with no or minimal BM disease prior to stem
      cell collection and does not influence outcome in univariate and multivariate
      analysis. The presence of MRD at time of harvest is a strong outcome predictor.
      However, these results will have to be verified in a large prospective study.

PMID- 25939776
TI  - Crystal structures of benzoxazolyl-copper(iII,II,I) complexes and investigation
      of Cu(II)-mediated aryl carbon-hydrogen bromination.
AB  - Copper complexes have been frequently involved in many Cu-mediated carbon
      hydrogen halogenation reactions. We fortunately obtained three different valence
      benzoxazolyl-copper complexes, along with aryl carbon-hydrogen bromination, in
      the self-assembly reaction of ligands with CuBr2. The complexes have been
      successfully characterized by X-ray single crystal diffraction analyses. The
      results indicate that 1 consists of di-brominated p-benzoxazolylphenylamine (L)
      and an unusual high valence copper(III) complex with tetrahedral geometry, 2 is
      the first polymeric catenulate di-brominated benzoxazolyl-copper(I) complex and 3
      is the mono-brominated benzoxazolyl-copper(II) complex. We speculate proposed
      mechanisms for the formation of these complexes and the bromination of aryl
      carbon-hydrogen based on these crystal structures.

PMID- 25939778
TI  - Vagus nerve modulation of inflammation: Cardiovascular implications.
AB  - The vagus nerve modulates inflammatory responses in various organ systems.
      Emerging evidence indicates that the vagus can have profound and complex effects
      on cardiovascular function, remodeling, arrhythmias, and mortality by several
      mechanisms. In heart failure and during ischemia, an adverse inflammatory
      response can occur. The vagus nerve may modulate cardiovascular disease and
      outcomes by affecting inflammatory responses. Here, evidence for and components
      of the vagus inflammatory reflex are reviewed and evidence for and implications
      of effects of vagus activation on inflammation in the cardiovascular system are
      considered. 

PMID- 25939777
TI  - Can empirical hypertonic saline or sodium bicarbonate treatment prevent the
      development of cardiotoxicity during serious amitriptyline poisoning?
      Experimental research.
AB  - OBJECTIVE: The aim of this experimental study was to investigate whether
      hypertonic saline or sodium bicarbonate administration prevented the development
      of cardiotoxicity in rats that received toxic doses of amitriptyline. METHOD:
      Thirty-six Sprague Dawley rats were used in the study. The animals were divided
      into six groups. Group 1 received toxic doses of i.p. amitriptyline. Groups 2 and
      3 toxic doses of i.p. amitriptyline, plus i.v. sodium bicarbonate and i.v.
      hypertonic saline, respectively. Group 4 received only i.v. sodium bicarbonate,
      group 5 received only i.v. hypertonic saline, and group 6 was the control.
      Electrocardiography was recorded in all rats for a maximum of 60 minutes. Blood
      samples were obtained to measure the serum levels of sodium and ionised calcium.
      RESULTS: The survival time was shorter in group 1. In this group, the animals'
      heart rates also decreased over time, and their QRS and QTc intervals were
      significantly prolonged. Groups 2 and 3 showed less severe changes in their ECGs
      and the rats survived for a longer period. The effects of sodium bicarbonate or
      hypertonic saline treatments on reducing the development of cardiotoxicity were
      similar. The serum sodium levels decreased in all the amitriptyline-applied
      groups. Reduction of serum sodium level was most pronounced in group 1.
      CONCLUSION: Empirical treatment with sodium bicarbonate or hypertonic saline can
      reduce the development of cardiotoxicity during amitriptyline intoxication. As
      hypertonic saline has no adverse effects on drug elimination, it should be
      considered as an alternative to sodium bicarbonate therapy.

PMID- 25939779
TI  - Dynamic interplay between catalytic and lectin domains of GalNAc-transferases
      modulates protein O-glycosylation.
AB  - Protein O-glycosylation is controlled by polypeptide GalNAc-transferases (GalNAc
      Ts) that uniquely feature both a catalytic and lectin domain. The underlying
      molecular basis of how the lectin domains of GalNAc-Ts contribute to glycopeptide
      specificity and catalysis remains unclear. Here we present the first crystal
      structures of complexes of GalNAc-T2 with glycopeptides that together with
      enhanced sampling molecular dynamics simulations demonstrate a cooperative
      mechanism by which the lectin domain enables free acceptor sites binding of
      glycopeptides into the catalytic domain. Atomic force microscopy and small-angle
      X-ray scattering experiments further reveal a dynamic conformational landscape of
      GalNAc-T2 and a prominent role of compact structures that are both required for
      efficient catalysis. Our model indicates that the activity profile of GalNAc-T2
      is dictated by conformational heterogeneity and relies on a flexible linker
      located between the catalytic and the lectin domains. Our results also shed light
      on how GalNAc-Ts generate dense decoration of proteins with O-glycans. 

PMID- 25939780
TI  - Uterine-derived progenitor cells are immunoprivileged and effectively improve
      cardiac regeneration when used for cell therapy.
AB  - Cell therapy to prevent cardiac dysfunction after myocardial infarction (MI) is
      less effective in aged patients because aged cells have decreased regenerative
      capacity. Allogeneic transplanted stem cells (SCs) from young donors are usually
      rejected. Maintaining transplanted SC immunoprivilege may dramatically improve
      regenerative outcomes. The uterus has distinct immune characteristics, and we
      showed that reparative uterine SCs home to the myocardium post-MI. Here, we
      identify immunoprivileged uterine SCs and assess their effects on cardiac
      regeneration after allogeneic transplantation. We found more than 20% of cells in
      the mouse uterus have undetectable MHC I expression by flow cytometry. Uterine
      MHC I((neg)) and MHC I((pos)) cells were separated by magnetic cell sorting. The
      MHC I((neg)) population expressed the SC markers CD34, Sca-1 and CD90, but did
      not express MHC II or c-kit. In vitro, MHC I((neg)) and ((pos)) SCs show colony
      formation and endothelial differentiation capacity. In mixed leukocyte co
      culture, MHC I((neg)) cells showed reduced cell death and leukocyte proliferation
      compared to MHC I((pos)) cells. MHC I((neg)) and ((pos)) cells had significantly
      greater angiogenic capacity than mesenchymal stem cells. The benefits of
      intramyocardial injection of allogeneic MHC I((neg)) cells after MI were
      comparable to syngeneic bone marrow cell transplantation, with engraftment in
      cardiac tissue and limited recruitment of CD4 and CD8 cells up to 21 days post
      MI. MHC I((neg)) cells preserved cardiac function, decreased infarct size and
      improved regeneration post-MI. This new source of immunoprivileged cells can
      induce neovascularization and could be used as allogeneic cell therapy for
      regenerative medicine.

PMID- 25939782
TI  - Clear aligners generations and orthodontic tooth movement.
AB  - Clear aligner technology has evolved over the last 15 years, with these
      appliances continually being modified to increase the range of tooth movements
      that they can achieve. However, there is very little clinical research available
      to show how these appliances achieve their results. This article describes the
      different generations of clear aligners that are available and highlights their
      use. However, until more clinical research becomes available, aligners cannot be
      routinely prescribed as an effective alternative to fixed labial appliances. 

PMID- 25939781
TI  - The effects of item familiarity on the neural correlates of successful
      associative memory encoding.
AB  - Associative memory is considered to be resource-demanding, requiring individuals
      to learn individual items and the specific relationships between those items.
      Previous research has shown that prior studying of items aids in associative
      memory for pairs composed of those same items, as compared to pairs of items that
      have not been prelearned (e.g., Kilb & Naveh-Benjamin, 2011). In the present
      study, we sought to elucidate the neural correlates mediating this memory
      facilitation. After being trained on individual items, participants were scanned
      while encoding item pairs composed of items from the pretrained phase
      (familiarized-item pairs) and pairs whose items had not been previously learned
      (unfamiliarized-item pairs). Consistent with previous findings, the overall
      subsequent recollection showed the engagement of bilateral parahippocampal gyrus
      (PHG) and hippocampus, when compared to subsequent forgetting. However, a direct
      comparison between familiarized- and unfamiliarized-item pairs showed that
      subsequently recollected familiarized-item pairs were associated with decreased
      activity across much of the encoding network, including bilateral PHG,
      hippocampus, prefrontal cortex, and regions associated with item-specific
      processing within occipital cortex. Increased activity for familiarized-item
      pairs was found in a more limited set of regions, including bilateral parietal
      cortex, which has been associated with the formation of novel associations.
      Additionally, activity in the right parietal cortex correlated with associative
      memory success in the familiarized condition. Taken together, these results
      suggest that prior exposure to items can reduce the demands incurred on neural
      processing throughout the associative encoding network and can enhance
      associative memory performance by focusing resources within regions supporting
      the formation of associative links. 

PMID- 25939783
TI  - Plumbagin protects against glucocorticoid-induced osteoporosis through Nrf-2
      pathway.
AB  - Long-term and high-dose glucocorticoids (GCs) supplementation has been linked to
      osteoporosis. In this study, we studied the protective role of plumbagin against
      GC-induced cell damage in MC3T3-E1 cells. The effect of dexamethasone (DEX) and
      plumbagin on cell viability was determined. DEX showed as IC-50 value of 95 MUM.
      Further, 10 MUM plumbagin treatment effectively ameliorated DEX-induced cell
      death by increasing the cell viability to 92 %. A further effect of plumbagin on
      DEX-induced oxidative stress was determined through reactive oxygen species (ROS)
      level, lipid peroxide content, and antioxidant status. Nrf-2 nuclear localization
      was analyzed through immunofluorescence. Protein expression of redox regulator
      Nrf-2 and their target genes HO-1 and NQO1 and osteogenic markers (OCN, OPN Runx
      2) were determined by Western blot. Apoptotic effect was analyzed by
      mitochondrial membrane potential and caspase activities (3, 8, and 9). The
      results showed that DEX treatment showed a significant increase in oxidative
      stress through increased ROS levels and downregulation of cytoprotective
      antioxidant proteins and antioxidant enzyme activities. Further DEX treatment
      downregulated the osteogenic markers and upregulated apoptosis through decreased
      mitochondrial membrane potential and upregulation of caspase activities.
      Plumbagin treatment significantly reversed the levels of oxidative stress and
      apoptotic markers and protected against DEX-induced cell damage. Further,
      plumbagin treatment significantly improved the expression of osteogenic markers
      compared to DEX treatment. In conclusion, the present study shows that plumbagin
      offers significant protective role against DEX-induced cellular damage via
      regulating oxidative stress, apoptosis, and osteogenic markers.

PMID- 25939784
TI  - Novel cystathionine beta-synthase gene mutations in a Filipino patient with
      classic homocystinuria.
AB  - BACKGROUND: Classic homocystinuria due to cystathionine beta-synthase (CBS)
      deficiency is an autosomal recessive disorder of sulfur metabolism. Clinical
      manifestations include mental retardation, dislocation of the optic lens (ectopia
      lentis), skeletal abnormalities and a tendency to thromboembolic episodes. We
      present the first mutational analysis of CBS in a Filipino patient with classic
      homocystinuria. METHODS: Genomic DNA was extracted from peripheral blood
      collected from a diagnosed Filipino patient with classic homocystinuria. The
      entire coding region of CBS (17 exons) was amplified using polymerase chain
      reaction and bidirectionally sequenced using standard protocols. RESULTS: The
      patient was found to be compound heterozygous for two novel mutations, g.13995G>A
      [c.982G>A; p.D328K] and g.15860-15868dupGCAGGAGCT [c.1083-1091dupGCAGGAGCT; p.
      Q362-L364dupQEL]. Four known single-nucleotide polymorphisms (rs234706,
      rs1801181, rs706208 and rs706209) were also detected in the present patient's
      CBS. The patient was heterozygous for all the identified alleles. CONCLUSIONS:
      This is the first mutational analysis of CBS done in a Filipino patient with
      classic homocystinuria who presented with a novel duplication mutation and a
      novel missense mutation. Homocystinuria due to CBS deficiency is a heterogeneous
      disorder at the molecular level.

PMID- 25939785
TI  - Pollen-derived adenosine is a necessary cofactor for ragweed allergy.
AB  - BACKGROUND: Ragweed (Ambrosia artemisiifolia) is a strong elicitor of allergic
      airway inflammation with worldwide increasing prevalence. Various components of
      ragweed pollen are thought to play a role in the development of allergic
      responses. The aim of this study was to identify critical factors for
      allergenicity of ragweed pollen in a physiological model of allergic airway
      inflammation. METHODS: Aqueous ragweed pollen extract, the low molecular weight
      fraction or the major allergen Amb a 1 was instilled intranasally on 1-11
      consecutive days, and allergic airway inflammation was evaluated by
      bronchoalveolar lavage, lung histology, serology, gene expression in lung tissue,
      and measurement of lung function. Pollen-derived adenosine was removed from the
      extract enzymatically to analyze its role in ragweed-induced allergy. Migration
      of human neutrophils and eosinophils toward supernatants of ragweed-stimulated
      bronchial epithelial cells was analyzed. RESULTS: Instillation of ragweed pollen
      extract, but not of the major allergen or the low molecular weight fraction,
      induced specific IgG1 , pulmonary infiltration with inflammatory cells, a Th2
      associated cytokine signature in pulmonary tissue, and impaired lung function.
      Adenosine aggravated ragweed-induced allergic lung inflammation. In vitro, human
      neutrophils and eosinophils migrated toward supernatants of bronchial epithelial
      cells stimulated with ragweed extract only if adenosine was present. CONCLUSIONS:
      Pollen-derived adenosine is a critical factor in ragweed-pollen-induced allergic
      airway inflammation. Future studies aim at therapeutic strategies to control
      these allergen-independent pathways.

PMID- 25939786
TI  - Might apixaban be the optimal oral anticoagulant for haemophiliacs with atrial
      fibrillation?

PMID- 25939787
TI  - Current Views on Anthracycline Cardiotoxicity in Childhood Cancer Survivors.
AB  - Owing to their high efficacy, anthracycline antibiotics are included in numerous
      chemotherapeutic regimens used-often in combination with radiation therapy and/or
      surgery-in treatment of solid tumours and blood malignancies, both in children
      and adults. However, the efficacy of modern cancer treatments, owing to which the
      population of cancer survivors has been on the rise in recent years, may be
      limited by the risk of serious complications involving multiple organs and
      systems, including the cardiovascular system. Being an important side effect of
      anthracyclines, cardiotoxicity may limit the efficacy of cancer therapies in the
      acute phase (i.e. during the treatment) and induce the long-term sequelae,
      observed years after treatment completion in childhood cancer survivors. It is
      very important to understand the cardiotoxicity-associated mechanisms and to
      determine its risk factors in order to develop and/or improve the effective
      countermeasures. Based on published data, the paper provides an outline of
      current views on anthracycline cardiotoxicity and discusses such aspects as
      molecular mechanisms of cardiotoxicity and its clinical manifestations as well as
      the new preventive strategies and diagnostic techniques used for the assessment
      of cardiovascular abnormalities. The widespread awareness of cancer treatment
      related cardiotoxicity among the healthcare professionals may significantly
      improve the quality of life of the childhood cancer survivors. 

PMID- 25939788
TI  - Real-time monitoring of the mitophagy process by a photostable fluorescent
      mitochondrion-specific bioprobe with AIE characteristics.
AB  - An isothiocyanate-functionalized tetraphenylethene is synthesized and used as a
      fluorescent bioprobe for mitochondrion imaging with high specificity and
      photostability. The covalent conjugation of the bioprobe to mitochondrial
      proteins endows it with high resistance to microenvironmental changes, enabling
      it for real-time monitoring of mitophagy. 

PMID- 25939789
TI  - Considerations for the utilization of 'comparative analysis of colorimetric
      staining in skin using open-source software' in an experimental setting.

PMID- 25939798
TI  - Efficient intracellular delivery and improved biocompatibility of colloidal
      silver nanoparticles towards intracellular SERS immuno-sensing.
AB  - High throughput intracellular delivery strategies, electroporation, passive and
      TATHA2 facilitated diffusion of colloidal silver nanoparticles (AgNPs) are
      investigated for cellular toxicity and uptake using state-of-art analytical
      techniques. The TATHA2 facilitated approach efficiently delivered high payload
      with no toxicity, pre-requisites for intracellular applications of plasmonic
      metal nanoparticles (PMNPs) in sensing and therapeutics. 

PMID- 25939797
TI  - The modifying effect of vitamin C on the association between perfluorinated
      compounds and insulin resistance in the Korean elderly: a double-blind,
      randomized, placebo-controlled crossover trial.
AB  - PURPOSE: There is limited evidence whether environmental exposure to
      perfluorinated compounds (PFCs) affects insulin resistance (IR) and whether
      vitamin C intake protects against the adverse effect of PFCs. This study was
      carried out to investigate the effect of PFCs on IR through oxidative stress, and
      the effects of a 4-week consumption of vitamin C supplement compared placebo on
      development of IR by PFCs. METHODS: For a double-blind, community-based,
      randomized, placebo-controlled crossover intervention of vitamin C, we assigned
      141 elderly subjects to both vitamin C and placebo treatments for 4 weeks. We
      measured serum levels of PFCs to estimate PFC exposures and urinary levels of
      malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) for oxidative
      stress. We also measured levels of fasting glucose and insulin and derived the
      homeostatic model assessment (HOMA) index to assess IR. RESULTS: Perfluorooctane
      sulfonate (PFOS) and perfluorododecanoic acid (PFDoDA) levels were found to be
      positively associated with HOMA index at the baseline and after placebo
      treatment. Risks of IR for the top decile of PFOS and PFDoDA exposures were
      significantly elevated compared with those with lower PFOS and PFDoDA exposures
      (both, P < 0.0001). However, the effects of PFOS and PFDoDA on HOMA disappeared
      after vitamin C supplementation (both, P > 0.30). Furthermore, PFOS and PFDoDA
      levels were also significantly associated with MDA and 8-OHdG levels, and MDA
      levels were positively associated with HOMA index. CONCLUSION: PFOS and PFDoDA
      exposures were positively associated with IR and oxidative stress, and vitamin C
      supplementation protected against the adverse effects of PFOS and PFDoDA on IR.

PMID- 25939799
TI  - The relationship between income and oral health among people with intellectual
      disabilities: a global perspective.
AB  - BACKGROUND: The scientific literature cites wide health disparities for people
      with intellectual disabilities compared to the general population. This study
      seeks to gain an understanding of the effects of income status on oral health in
      a global population of people with intellectual disabilities. METHODS: Eighty-two
      thousand five hundred and seventy Special Olympics athletes were screened and
      eligible for inclusion in this study. The main exposure (income status) and
      selected oral health signs and symptoms (missing teeth, untreated decay, injury,
      gingivitis, and mouth pain) were used to conduct a cross-sectional analysis.
      Prevalence odds ratios were obtained through logistic regression. RESULTS: Study
      participants from low-income countries experienced adverse health outcomes at a
      lower rate than expected. Study participants from upper middle, lower middle, and
      low-income countries had higher odds of mouth pain and untreated decay, yet lower
      odds of missing teeth, injury, and gingivitis, than participants from high-income
      countries. Overall, a great number of individuals from every income group
      required maintenance or urgent care. CONCLUSION: Oral health problems are not
      exclusive to low-income study participants. Unexpectedly high odds of missing
      teeth, injury, and gingivitis in high-income countries may be attributed to the
      high proportion of participants from the United States, which is considered a
      high-income country but has large income disparities. Health-determining
      circumstances in low-income countries provide some protection from the
      hypothesized gradient of oral health for all measured outcomes.

PMID- 25939800
TI  - Fabrication of silk fibroin film using centrifugal casting technique for corneal
      tissue engineering.
AB  - Films prepared from silk fibroin have shown potential as biomaterials in tissue
      engineering applications for the eye. Here, we present a novel process for
      fabrication of silk fibroin films for corneal application. In this work,
      fabrication of silk fibroin films was simply achieved by centrifugal force. In
      contrast to the conventional dry casting method, we carried out the new process
      in a centrifuge with a rotating speed of 4000 rpm, where centrifugal force was
      imposed on an aluminum tube containing silk fibroin solution. In the present
      study, we also compared the surface roughness, mechanical properties,
      transparency, and cell proliferation between centrifugal and dry casting method.
      In terms of surface morphology, films fabricated by the centrifugal casting have
      less surface roughness than those by the dry casting. For elasticity and
      transparency, silk fibroin films obtained from the centrifugal casting had
      favorable results compared with those prepared by dry casting. Furthermore,
      primary human corneal keratocytes grew better in films prepared by the
      centrifugal casting. Therefore, our results suggest that this new fabrication
      process for silk fibroin films offers important potential benefits for corneal
      tissue regeneration.

PMID- 25939801
TI  - Human ciliary neurotrophic factor-overexpressing stable bone marrow stromal cells
      in the treatment of a rat model of traumatic spinal cord injury.
AB  - BACKGROUND AIMS: Traumatic injury to the central nervous system (CNS) often
      causes motor dysfunctions. However, because of the CNS complexity and variability
      in the clinical presentations, efforts to repair damaged CNS tissue and restoring
      its functions are particularly demanding. On the other hand, recent progress in
      the regenerative therapy field have led to novel approaches for the treatment of
      traumatic CNS injury and renewed hopes to overcome the obstacles. It appears that
      the balance between neurite re-growth-inhibiting and neurite re-growth-inducing
      molecules determines the axonal re-growth fate. Neurotrophic factors can tilt
      this balance and indeed promote cell survival and axonal re-growth over
      neurodegeneration. One of the promising neurotrophic factors in this field is
      ciliary neurotrophic factor (CNTF). METHODS: We transfected rat bone marrow
      stromal cells with a mammalian expression vector-inserted human CNTF gene through
      the use of a non-viral method to prepare human CNTF-overexpressing stem cells
      under ex vivo conditions. We transplanted these modified cells to the rat model
      of spinal cord traumatic injury to explore functional recovery after contusion
      induction. RESULTS: Our data from immunocytochemistry and behavioral tests showed
      that such cells can act as a powerful potential approach to treat traumatic CNS
      injuries because these modified cells improved the behavioral test scores in the
      rat model of spinal cord injury. CONCLUSIONS: CNTF-overexpressing bone marrow
      stromal cells can ameliorate spinal cord traumatic injury and can be used in the
      treatment of traumatic CNS injuries in the near future.

PMID- 25939802
TI  - Paracrine action of mesenchymal stromal cells delivered by microspheres
      contributes to cutaneous wound healing and prevents scar formation in mice.
AB  - BACKGROUND AIMS: Accumulating evidence suggests that mesenchymal stromal cells
      (MSCs) participate in wound healing to favor tissue regeneration and inhibit
      fibrotic tissue formation. However, the evidence of MSCs to suppress cutaneous
      scar is extremely rare, and the mechanism remains unidentified. This study aimed
      to demonstrate whether MSCs-as the result of their paracrine actions on damaged
      tissues-would accelerate wound healing and prevent cutaneous fibrosis. METHODS:
      For efficient delivery of MSCs to skin wounds, microspheres were used to maintain
      MSC potency. Whether MSCs can accelerate wound healing and alleviate cutaneous
      fibrosis through paracrine action was investigated with the use of a Transwell co
      culture system in vitro and a murine model in vivo. RESULTS: MSCs cultured on
      gelatin microspheres fully retained their cell surface marker expression profile,
      proliferation, differentiation and paracrine potential. Co-cultures of MSCs and
      fibroblasts indicated that the benefits of MSCs on suppressing fibroblast
      proliferation and its fibrotic behavior induced by inflammatory cytokines
      probably were caused by paracrine actions. Importantly, microspheres successfully
      delivered MSCs into wound margins and significantly accelerated wound healing and
      concomitantly reduced the fibrotic activities of cells within the wounds and
      excessive accumulation of extracellular matrix as well as the transforming growth
      factor-beta1/transforming growth factor-beta3 ratio. CONCLUSIONS: This study
      provides insight into what we believe to be a previously undescribed,
      multifaceted role of MSC-released protein in reducing cutaneous fibrotic
      formation. Paracrine action of MSCs delivered by microspheres may thus qualify as
      a promising strategy to enhance tissue repair and to prevent excessive fibrosis
      during cutaneous wound healing.

PMID- 25939804
TI  - Palladium-assisted "aromatic metamorphosis" of dibenzothiophenes into
      triphenylenes.
AB  - Two new palladium-catalyzed reactions of aromatic sulfur compounds enabled the
      conversion of dibenzothiophenes into triphenylenes in four steps. This
      transformation of one aromatic framework into another consists of 1) 4
      chlorobutylation of the dibenzothiophene to form the corresponding sulfonium
      salt, 2) palladium-catalyzed arylative ring opening of the sulfonium salt with a
      sodium tetraarylborate, 3) an intramolecular S(N)2 reaction to form a teraryl
      sulfonium salt, and 4) palladium-catalyzed intramolecular C-S/C-H coupling
      through electrophilic palladation. Symmetrical as well as unsymmetrical
      triphenylenes of interest were synthesized in a tailor-made fashion in
      satisfactory overall yields.

PMID- 25939803
TI  - Giardia duodenalis assemblages in Egyptian children with diarrhea.
AB  - Giardia duodenalis is considered the most common cause of parasitic diarrhea
      worldwide. Genetic studies revealed that at least eight assemblages (A-H) exist.
      Of these assemblages, A and B are found primarily in human beings and
      occasionally in animals. The association between clinical symptoms and G.
      duodenalis assemblages is controversial. The aim of the present study was to
      determine the assemblages of G. duodenalis prevalent among Egyptian children with
      diarrhea. Therefore, 96 positive stool samples for Giardia by light microscopy
      were subjected to multilocus genotyping targeting the triose phosphate isomerase
      (tpi), beta-giardin (bg), and glutamate dehydrogenase (gdh) genes. Amplified
      polymerase chain reaction (PCR) products were then purified, sequenced, and
      aligned with reference strains to determine the assemblages of the Giardia
      isolates. Out of the 96 microscopically positive stool samples for Giardia, 77
      (80 %) were successfully amplified and sequenced at least at one locus. Of these,
      21 (27.3 %) were shown to be assemblage A, 54 (70.1 %) assemblage B, while
      discordant sequence typing results were observed in 2 (2.6 %) samples. AII was
      the predominant subassemblage of assemblage A, while it was generally difficult
      to further classify assemblage B. It was concluded that infection with assemblage
      B was more common than that with assemblage A. No associations between
      epidemiological information and assemblage were detected, except with age.
      Although infections with assemblage B were more frequently associated with
      abdominal pain and acute diarrhea than with assemblage A, the difference was not
      statistically significant. 

PMID- 25939805
TI  - Lead-resistant strain KQBT-3 inoculants of Tricholoma lobayensis Heim that
      enhance remediation of lead-contaminated soil.
AB  - To enhance lead-detoxifying efficiency of Tricholoma lobayensis Heim, one lead
      resistant strain KQBT-3 (Bacillus thuringiensis) was applied owing to its
      excellent ability to tolerate Pb. KQBT-3 domesticated in liquid medium with
      increasing lead concentrations could tolerate Pb(NO3)2 up to a concentration of
      800 mg L(-1). Pot experiments showed that the KQBT-3 not only could promote the
      growth of T. lobayensis, but also could enhance its Pb accumulation ability under
      heavy metal stress. Biomass and accumulation of Pb increased 47.3% and 33.2%,
      respectively. In addition, after inoculation of KQBT-3, the significant decrease
      of malondialdehyde indicated KQBT-3 could alleviate lipid peroxidation in T.
      lobayensis. What is interesting is that superoxide dismutase and peroxidase
      activities in T. lobayensis inoculated with KQBT-3 were increased, and the
      maximum increasing rate was 121.71% and 117.29%, respectively. However, the
      catalase activity increased slightly. This revealed that inoculating KQBT-3
      further induced oxidative response in T. lobayensis due to Pb accumulation.
      Therefore, the present work showed that KQBT-3 made a major contribution to
      promote growth and lead uptake of T. lobayensis and alleviate the oxidative
      stress. This kind of auxiliary effect on macrofungi can be developed into a novel
      bioremediation strategy.

PMID- 25939806
TI  - Changes in the pattern of paracetamol use in the periconception period in a
      Danish cohort.
AB  - Paracetamol is the most commonly used over-the-counter drug in pregnancy. It is
      generally considered to be safe, but prolonged antenatal exposure has been
      associated with offspring short- and long-term morbidity. Our aim was to describe
      the pattern of paracetamol use with a focus on frequent ingestion (more than once
      a week), 3 months before and in early pregnancy. In this cohort, 8650 pregnant
      women responded to a web-based clinical questionnaire that included questions
      about drug use. Paracetamol was the most used drug before and in early pregnancy
      (35.2% and 6.5% of respondents, respectively). The proportion of frequent users
      decreased from 3.9% before to 0.9% in early pregnancy. Frequent paracetamol use
      was associated with smoking, co-morbidities, body mass index >= 25 kg/m(2),
      unplanned pregnancy, no education and inability to understand Danish. A
      significant decrease in the proportion of women with any paracetamol use in early
      pregnancy was noted after access to large packs was restricted by legislation.

PMID- 25939807
TI  - Core Competencies in Disaster Management and Humanitarian Assistance: A
      Systematic Review.
AB  - Disaster response demands a large workforce covering diverse professional
      sectors. Throughout this article, we illustrate the results of a systematic
      review of peer-reviewed studies to identify existing competency sets for disaster
      management and humanitarian assistance that would serve as guidance for the
      development of a common disaster curriculum. A systematic review of English
      language articles was performed on PubMed, Google Scholar, Scopus, ERIC, and
      Cochrane Library. Studies were included if reporting competency domains,
      abilities, knowledge, skills, or attitudes for professionals involved disaster
      relief or humanitarian assistance. Exclusion criteria included abstracts,
      citations, case studies, and studies not dealing with disasters or humanitarian
      assistance. Thirty-eight papers were analyzed. Target audience was defined in all
      articles. Five references (13%) reported cross-sectorial competencies. Most of
      the articles (81.6%) were specific to health care. Eighteen (47%) papers included
      competencies for at least 2 different disciplines and 18 (47%) for different
      professional groups. Nursing was the most widely represented cadre. Eighteen
      papers (47%) defined competency domains and 36 (94%) reported list of
      competencies. Nineteen articles (50%) adopted consensus-building to define
      competencies, and 12 (31%) included competencies adapted to different
      professional responsibility levels. This systematic review revealed that the
      largest number of papers were mainly focused on the health care sector and
      presented a lack of agreement on the terminology used for competency-based
      definition.

PMID- 25939808
TI  - Electrochemical properties and applications of nanocrystalline, microcrystalline,
      and epitaxial cubic silicon carbide films.
AB  - Microstructures of the materials (e.g., crystallinitiy, defects, and composition,
      etc.) determine their properties, which eventually lead to their diverse
      applications. In this contribution, the properties, especially the
      electrochemical properties, of cubic silicon carbide (3C-SiC) films have been
      engineered by controlling their microstructures. By manipulating the deposition
      conditions, nanocrystalline, microcrystalline and epitaxial (001) 3C-SiC films
      are obtained with varied properties. The epitaxial 3C-SiC film presents the
      lowest double-layer capacitance and the highest reversibility of redox probes,
      because of its perfect (001) orientation and high phase purity. The highest
      double-layer capacitance and the lowest reversibility of redox probes have been
      realized on the nanocrystalline 3C-SiC film. Those are ascribed to its high
      amount of grain boundaries, amorphous phases and large diversity in its crystal
      size. Based on their diverse properties, the electrochemical performances of 3C
      SiC films are evaluated in two kinds of potential applications, namely an
      electrochemical capacitor using a nanocrystalline film and an electrochemical
      dopamine sensor using the epitaxial 3C-SiC film. The nanocrystalline 3C-SiC film
      shows not only a high double layer capacitance (43-70 MUF/cm(2)) but also a long
      term stability of its capacitance. The epitaxial 3C-SiC film shows a low
      detection limit toward dopamine, which is one to 2 orders of magnitude lower than
      its normal concentration in tissue. Therefore, 3C-SiC film is a novel but
      designable material for different emerging electrochemical applications such as
      energy storage, biomedical/chemical sensors, environmental pollutant detectors,
      and so on. 

PMID- 25939809
TI  - Design of Hydrogels for Biomedical Applications.
AB  - Hydrogels are considered key tools for the design of biomaterials, such as wound
      dressings, drug reservoirs, and temporary scaffolds for cells. Despite their
      potential, conventional hydrogels have limited applicability under wet
      physiological conditions because they suffer from the uncontrollable temporal
      change in shape: swelling takes place immediately after the installation. Swollen
      hydrogels easily fail under mechanical stress. The morphological change may cause
      not only the slippage from the installation site but also local nerve
      compression. The design of hydrogels that can retain their original shape and
      mechanical properties in an aqueous environment is, therefore, of great
      importance. On the one hand, the controlled degradation of used hydrogels has to
      be realized in some biomedical applications. This Progress Report provides a
      brief overview of the recent progress in the development of hydrogels for
      biomedical applications. Practical approaches to control the swelling properties
      of hydrogels are discussed. The designs of hydrogels with controlled degradation
      properties as well as the theoretical models to predict the degradation behavior
      are also introduced. Moreover, current challenges and limitation toward
      biomedical applications are discussed, and future directions are offered. 

PMID- 25939810
TI  - TWO INNEXINS OF Spodoptera litura INFLUENCES HEMICHANNEL AND GAP JUNCTION
      FUNCTIONS IN CELLULAR IMMUNE RESPONSES.
AB  - Insect cellular immune responses include encapsulation, nodule formation, and
      phagocytosis. Hemichannels and gap junctions are involved in these cellular
      actions. Innexins (Inxs: analogous to the vertebrate connexins) form hemichannels
      and gap junctions, but the molecular mechanisms underlying their biology is still
      unclear. In this article, we reported a steady-state level of Inxs (SpliInxs) in
      hemocytes of Spodoptera litura, which formed nonfunctional hemichannels on the
      cell surface to maintain normal metabolism. We also reported that two innnexins
      (SpliInx2 and SpliInx3) were expressed significantly higher in hemocytes compared
      to other tissues, suggesting that they play important roles in hemocytes. Amino
      acid analysis found that two cysteine residues in two extracellular loops
      provided the capability for SpliInx2 and SpliInx3 hemichannels to dock into gap
      junctions. Western blotting demonstrated that both extracellular and
      intracellular loops of SpliInx3 and the extracellular loops of SpliInx2 might
      undergo posttranslational modification during the formation of a steady-state
      hemichannel. During hemichannel formation, SpliInx2 presented as one isoform,
      while SpliInx3 presented as three isoforms. These results provide fundamental
      knowledge for further study of how steady-state levels of SpliInxs are
      dynamically adjusted to perform cellular immune responses under immune challenge.

PMID- 25939812
TI  - Skin equivalents: skin from reconstructions as models to study skin development
      and diseases.
AB  - While skin is readily available for sampling and direct studies of its
      constituents, an important intermediate step is to design in vitro and/or in vivo
      models to address scientific or medical questions in dermatology and skin
      biology. Pioneered more than 30 years ago, human skin equivalents (HSEs) have
      been refined with better cell culture techniques and media, together with
      sophisticated cell biology tools including genetic engineering and cell
      reprogramming. HSEs mimic key elements of human skin biology and have been
      instrumental in demonstrating the importance of cell-cell interactions in skin
      homeostasis and the role of a complex cellular microenvironment to coordinate
      epidermal proliferation, differentiation and pigmentation. HSEs have a wide field
      of applications from cell biology to dermocosmetics, modelling diseases, drug
      development, skin ageing, pathophysiology and regenerative medicine. In this
      article we critically review the major current approaches used to reconstruct
      organotypic skin models and their application with a particular emphasis on skin
      biology and pathophysiology of skin disorders. 

PMID- 25939813
TI  - Impact of disinfectant wipes on the risk of Campylobacter jejuni infection during
      raw chicken preparation in domestic kitchens.
AB  - AIMS: In the present study, we conducted a quantitative microbial risk assessment
      forecasting the exposure to Campylobacter jejuni contaminated surfaces during
      preparation of chicken fillets and how using a disinfectant-wipe intervention to
      clean a contaminated work area decreases the risk of infection following the
      preparation of raw chicken fillet in a domestic kitchen. METHODS AND RESULTS:
      Using a Monte Carlo simulation of the risk of transferring Camp. jejuni strain
      A3249, from various surfaces to hands and subsequently transferring it to the
      mouth was forecasted. The use of a disinfectant-wipe intervention to disinfect
      contaminated surface area was also assessed. Several assumptions were used as
      input parameters in the classical Beta-Poisson model to determine the risk of
      infection. The disinfectant-wipe intervention reduced the risk of Camp. jejuni
      infection by 2-3 orders on all fomites. CONCLUSIONS: The use of disinfectant
      wipes after the preparation of raw chicken meat reduces the risk of Camp. jejuni
      infections. SIGNIFICANCE AND IMPACT OF THE STUDY: This risk assessment shows that
      the use of disinfectant wipes to decontaminate surface areas after chicken
      preparation reduces the annual risk of Camp. jejuni infections up to 99.2%,
      reducing the risk from 2 : 10 to 2 : 1000.

PMID- 25939811
TI  - The emerging molecular machinery and therapeutic targets of metastasis.
AB  - Metastasis is a 100-year-old research topic. Technological advances during the
      past few decades have led to significant progress in our understanding of
      metastatic disease. However, metastasis remains the leading cause of cancer
      related mortalities. The lack of appropriate clinical trials for metastasis
      preventive drugs and incomplete understanding of the molecular machinery are
      major obstacles in metastasis prevention and treatment. Numerous processes,
      factors, and signaling pathways are involved in regulating metastasis. Here we
      discuss recent progress in metastasis research, including epithelial-mesenchymal
      plasticity, cancer stem cells, emerging molecular determinants and therapeutic
      targets, and the link between metastasis and therapy resistance. 

PMID- 25939815
TI  - Excessive lipid-phagocytosis of neutrophils in a patient with mesothelioma.

PMID- 25939814
TI  - CREB-BDNF pathway influences alcohol cue-elicited activation in drinkers.
AB  - Alcohol use disorder (AUD) is suggested to have polygenic risk factors and also
      exhibits neurological complications, strongly encouraging a translational study
      to explore the associations between aggregates of genetic variants and brain
      function alterations related to alcohol use. In this study, we used a semiblind
      multivariate approach, parallel independent component analysis with multiple
      references (pICA-MR) to investigate relationships of genome-wide single
      nucleotide polymorphisms with alcohol cue-elicited brain activations in 315 heavy
      drinkers, where pICA-MR assesses multiple reference genes for their architecture
      and functional influences on neurobiological conditions. The genetic component
      derived from the cAMP-response element-binding protein and -brain derived
      neurotrophic factor (CREB-BDNF) pathway reference was significantly associated (r
      = -0.38, P = 3.98 * 10(-12) ) with an imaging component reflecting
      hyperactivation in precuneus, superior parietal lobule, and posterior cingulate
      for drinkers with more severe alcohol dependence symptoms. The highlighted brain
      regions participate in many cognitive processes and have been robustly implicated
      in craving-related studies. The genetic factor highlighted the CREB and BDNF
      references, as well as other genes including GRM5, GRM7, GRID1, GRIN2A, PRKCA,
      and PRKCB. Ingenuity Pathway Analysis indicated that the genetic component was
      enriched in synaptic plasticity, GABA, and protein kinase A signaling.
      Collectively, our findings suggest that genetic variations in various neural
      plasticity and signaling pathways partially explain the variance of precuneus
      reactivity to alcohol cues which appears to be associated with AUD severity.

PMID- 25939816
TI  - A step forward towards accurately assessing glomerular filtration rate in
      newborns.
AB  - In this edition of Pediatric Nephrology, Milena Treiber and colleagues have
      published a study on cystatin C (CysC) concentrations in relation to renal
      volumetry in 50 small-for-gestational age (SGA) and 50 appropriate-for
      gestational age (AGA) neonates, deriving a new formula for estimating neonatal
      glomerular filtration rate (GFR). The study builds on previous work which
      established that renal volumetry together with CysC blood levels is a superior
      method for establishing GFR in term and pre-term newborns [The Journal of
      Pediatrics (2014) 164:1026-1031.e2]. Treiber et al. use the expected difference
      between SGA and AGA renal volumes to document the superiority of their new
      formula, which is based on total renal volume, CysC and body surface area, but
      does not incorporate gold-standard inulin clearance. Treiber et al.'s study adds
      new knowledge to the field that will hopefully improve the safety of renally
      excreted critical dose drugs in the newborn period. This editorial discusses the
      strengths and limitations of the current study. 

PMID- 25939818
TI  - The role of universities in Australasian emergency medicine training.

PMID- 25939817
TI  - Podocyte directed therapy of nephrotic syndrome-can we bring the inside out?
AB  - Several of the drugs currently used for the treatment of glomerular diseases are
      prescribed for their immunotherapeutic or anti-inflammatory properties, based on
      the current understanding that glomerular diseases are mediated by immune
      responses. In recent years our understanding of podocytic signalling pathways and
      the crucial role of genetic predispositions in the pathology of glomerular
      diseases has broadened. Delineation of those signalling pathways supports the
      hypothesis that several of the medications and immunosuppressive agents used to
      treat glomerular diseases directly target glomerular podocytes. Several central
      downstream signalling pathways merge into regulatory pathways of the podocytic
      actin cytoskeleton and its connection to the slit diaphragm. The slit diaphragm
      and the cytoskeleton of the foot process represent a functional unit. A breakdown
      of the cytoskeletal backbone of the foot processes leads to internalization of
      slit diaphragm molecules, and internalization of slit diaphragm components in
      turn negatively affects cytoskeletal signalling pathways. Podocytes display a
      remarkable ability to recover from complete effacement and to re-form
      interdigitating foot processes and intact slit diaphragms after pharmacological
      intervention. This ability indicates an active inside-out signalling machinery
      which stabilizes integrin complex formations and triggers the recycling of slit
      diaphragm molecules from intracellular compartments to the cell surface. In this
      review we summarize current evidence from patient studies and model organisms on
      the direct impact of immunosuppressive and supportive drugs on podocyte
      signalling pathways. We highlight new therapeutic targets that may open novel
      opportunities to enhance and stabilize inside-out pathways in podocytes. 

PMID- 25939820
TI  - Multivalent aptamer-RNA based fluorescent probes for carrier-free detection of
      cellular microRNA-34a in mucin1-expressing cancer cells.
AB  - In this study, multivalent carrier-free aptamer-RNA based fluorescent probes (CF
      probes) were designed as a simpler, more reliable, timesaving strategy for
      cellular miRNA detection. CF-probes spontaneously delivered into cells without
      the need for additional carriers and visualized target microRNA-34a specifically.

PMID- 25939819
TI  - Consequences of additional use of contrast-enhanced (18)F-FDG PET/CT in target
      volume delineation and dose distribution for pancreatic cancer.
AB  - OBJECTIVE: To compare the differences between contrast-enhanced (CE) fluorine-18
      fludeoxyglucose ((18)F-FDG) positron emission tomography (PET)/CT and CECT in
      target volume delineation and radiotherapy (RT) dose distribution, and to
      evaluate the sparing of organs at risk (OARs) in the treatment plan of locally
      advanced pancreatic cancer (LAPC). METHODS: 21 consecutive patients with LAPC
      with histologically or cytologically confirmed adenocarcinoma underwent both non
      CECT and (18)F-FDG scans; 11 of whom also underwent CECT scans. Intensity
      modulated RT plans (prescribed dose, 54 Gy) were constructed to cover the
      corresponding gross tumour volume (GTV). The differences among GTVCT, GTVPET,
      GTVPET-CT and OARs in these different image sets as well as the uniformity of
      target dose were analysed. RESULTS: The mean non-CE GTVCT, GTVPET and GTVPET-CT
      were 76.9 +/- 47.8, 47.0 +/- 40.2 and 44.5 +/- 34.7 cm(3) (mean +/- standard
      deviation), respectively. The non-CE GTVPET-CT was significantly smaller than the
      non-CE GTVCT (p < 0.001). The CE GTVPET-CT was significantly smaller than the CE
      GTVCT (p = 0.033). For both the non-CE GTVCT and the CE GTVCT, the intestine V40
      (the percentage of the intestine volume irradiated by 40 Gy), intestine V50,
      intestine Dmax (the mean maximum dose), cord Dmax, left kidney V30, right kidney
      V30, left kidney Dmean (the mean dose), right kidney Dmean and liver V30 were
      5.90%, 2.52%, 5500 cGy, 2194 cGy, 3.40%, 0.68%, 747 cGy, 550 cGy and 5.37%,
      respectively. There are significant differences between the non-CE CT and the non
      CE PET-CT in intestine Dmax (p = 0.023) and right kidney Dmean (p = 0.029).
      CONCLUSION: Co-registration of (18)F-FDG PET with CECT may improve the accuracy
      of GTV delineation in LAPC and might reduce the adverse effect of irradiation.
      ADVANCES IN KNOWLEDGE: Individual adaptation of RT based on functional CE (18)F
      FDG PET/CT imaging is possible and highly promising in LAPC.

PMID- 25939821
TI  - Determination of delta-[L-alpha-aminoadipyl]-L-cysteinyl-D-valine in cell
      extracts of Penicillium chrysogenum using ion pair-RP-UPLC-MS/MS.
AB  - delta-[L-alpha-Aminoadipyl]-L-cysteinyl-D-valine (ACV) is a key intermediate in
      the biosynthesis pathway of penicillins and cephalosporins. Therefore, the
      accurate quantification of ACV is relevant, e.g. for kinetic studies on the
      production of these beta-lactam antibiotics. However, accurate quantification of
      ACV is a challenge, because it is an active thiol compound which, upon exposure
      to air, can easily react with other thiol compounds to form oxidized disulfides.
      We have found that, during exposure to air, the oxidation of ACV occurs both in
      aqueous standard solutions as well as in biological samples. Qualitative and
      quantitative determinations of ACV and the oxidized dimer bis-delta-[L-alpha
      aminoadipyl]-L-cysteinyl-D-valine have been carried out using ion pair reversed
      phase ultra high-performance liquid chromatography, hyphenated with tandem mass
      spectrometry (IP-RP-UPLC-MS/MS) as the analytical platform. We show that by
      application of tris(2-carboxy-ethyl)phosphine hydrochloride (TCEP) as the
      reducing reagent, the total amount of ACV can be determined, while using
      maleimide as derivatizing reagent enables to quantify the free reduced form only.

PMID- 25939822
TI  - Comparison of perioperative and short-term oncological outcomes after single- or
      multiport surgery for colorectal cancer.
AB  - AIM: The aim of this retrospective study was to compare the short-term surgical
      results of single-port surgery (SPS) with those of multiport surgery (MPS) for
      colorectal cancer. METHOD: We studied 673 consecutive patients who underwent SPS
      or MPS for colorectal cancer in our department from January 2008 to December
      2013. The operative parameters and oncological outcome were analysed and compared
      between the SPS and the MPS groups retrospectively. RESULTS: The SPS and MPS
      groups did not differ significantly in terms of preoperative evaluation. The
      median operative time was significantly shorter with SPS than with MPS (176 min
      vs 193 min; P < 0.001). The two groups did not differ significantly in terms of
      postoperative complications. Length of hospital stay was significantly shorter
      with SPS than with MPS (8 days vs 10 days; P < 0.001). Oncological resection was
      similar in the two groups. The disease-free survival rates at 2 years according
      to the TNM stage did not differ significantly between the two groups (Stage I,
      98.5% vs 94.7%; Stage II, 93.4% vs 90.7%; and Stage III, 70.8% vs 68.4%).
      CONCLUSION: Our experience demonstrates that SPS is safe and can provide
      oncological outcomes equal to those of MPS in patients with colorectal cancer.

PMID- 25939823
TI  - Cross-National Analysis of Beliefs and Attitude Toward Mental Illness Among
      Medical Professionals From Five Countries.
AB  - This quantitative study sought to compare beliefs about the manifestation, causes
      and treatment of mental illness and attitudes toward people with mental illness
      among health professionals from five countries: the United States, Brazil, Ghana,
      Nigeria, and China. A total of 902 health professionals from the five countries
      were surveyed using a questionnaire addressing attitudes towards people with
      mental illness and beliefs about the causes of mental illness. Chi-square and
      analysis of covariance (ANCOVA) were used to compare age and gender of the
      samples. Confirmatory factor analysis was employed to confirm the structure and
      fit of the hypothesized model based on data from a previous study that identified
      four factors: socializing with people with mental illness (socializing), belief
      that people with mental illness should have normal roles in society
      (normalizing), non-belief in supernatural causes (witchcraft or curses), and
      belief in bio-psycho-social causes of mental illness (bio-psycho-social).
      Analysis of Covariance was used to compare four factor scores across countries
      adjusting for differences in age and gender. Scores on all four factors were
      highest among U.S. professionals. The Chinese sample showed lowest score on
      socializing and normalizing while the Nigerian and Ghanaian samples were lowest
      on non-belief in supernatural causes of mental illness. Responses from Brazil
      fell between those of the U.S. and the other countries. Although based on
      convenience samples of health professional robust differences in attitudes among
      health professionals between these five countries appear to reflect underlying
      socio-cultural differences affecting attitudes of professionals with the greater
      evidence of stigmatized attitudes in developing countries. 

PMID- 25939824
TI  - Laparoscopic Fertility-preserving Treatment of a Pure Nongestational
      Choriocarcinoma of the Ovary: Case Report and Review of Current Literature.
AB  - This case report demonstrates the feasibility of laparoscopic and fertility
      preserving approach in nongestational choriocarcinoma of the ovary (NGCO). Pure
      NGCO is a rare malignant condition. In the last decade, only 14 cases have been
      reported in the literature. The use of laparoscopy and fertility-preserving
      procedures in nonepithelial ovarian malignancies is extremely controversial. A 23
      year-old woman underwent emergency laparoscopy due to acute abdominal pain
      associated with an 8-cm large adnexal mass. The initial procedure consisted only
      of a left oophoroplasty, and histology revealed a tumor of high malignant
      potential compatible with a primary NGCO. Approximately 3 weeks after initial
      surgery, she was submitted to a laparoscopic staging surgery, including left
      adnexectomy, omentectomy, peritoneal biopsies, and retroperitoneal
      lymphadenectomy. Final pathology confirmed an International Federation of
      Gynecology and Obstetrics stage IIB NGCO. Before initiation of adjuvant
      chemotherapy based on 3 courses of bleomycin, etoposide, and cisplatin, the
      patient received goserelin for ovarian suppression. Nine months after therapy,
      the patient presented no signs of recurrence and reassumed normal menstruation
      cycles with normal levels of gonadotropins and tumor markers. The current report
      brings new insights into the possibility of using use minimally invasive surgery
      and a combination of fertility-preserving methods for the treatment of NGCO.

PMID- 25939825
TI  - Dynamic and Reversible Polymorphism of Self-Assembled Lyotropic Liquid
      Crystalline Systems Derived from Cyclic Bis(ethynylhelicene) Oligomers.
AB  - A self-assembled lyotropic liquid crystal (LLC) system exhibiting dynamic and
      reversible polymorphism was developed using the synthetic cyclic ethynylhelicene
      oligomers cyclobis[(M)-D-n] (n = 4 and 6), in which two oligomer moieties are
      connected by two flexible linkers. The cyclic molecular structure was designed to
      control aggregation properties ranging from the molecular level to the
      macroscopic level. The cyclic oligomer changed its structure between random coils
      and an intramolecular homo-double helix induced by temperature and solvents. In
      the presence of pseudoenantiomeric acyclic oligomers, cyclobis[(M)-D-4] formed
      trimolecular complexes with a total molecular weight of over 10 000 Da containing
      two intermolecular hetero-double helices. The trimolecular complex formation
      predominated over bimolecular complex formation. The trimolecular complex self
      assembled at high concentrations and formed LLCs composed of anisotropically
      aligned fibers. The result is in contrast to acyclic systems, which form gels
      composed of randomly oriented fibers. The LLCs changed into turbid gels composed
      of randomly oriented bundles upon cooling, and the LLCs were regenerated by
      heating. This is a notable example of a self-assembled LLC system exhibiting
      dynamic and reversible polymorphism between two ordered structures in a closed
      system consisting of fully synthetic molecules. 

PMID- 25939826
TI  - Sensory and Quality Evaluation of Traditional Compared with Power Ultrasound
      Processed Corn (Zea Mays) Tortilla Chips.
AB  - Power ultrasound reduces the traditional corn steeping time from 18 to 1.5 h
      during tortilla chips dough (masa) processing. This study sought to examine
      consumer (n = 99) acceptability and quality of tortilla chips made from the masa
      by traditional compared with ultrasonic methods. Overall appearance, flavor, and
      texture acceptability scores were evaluated using a 9-point hedonic scale. The
      baked chips (process intermediate) before and after frying (finished product)
      were analyzed using a texture analyzer and machine vision. The texture values
      were determined using the 3-point bend test using breaking force gradient (BFG),
      peak breaking force (PBF), and breaking distance (BD). The fracturing properties
      determined by the crisp fracture support rig using fracture force gradient (FFG),
      peak fracture force (PFF), and fracture distance (FD). The machine vision
      evaluated the total surface area, lightness (L), color difference (DeltaE), Hue (
      degrees h), and Chroma (C*). The results were evaluated by analysis of variance
      and means were separated using Tukey's test. Machine vision values of L,  degrees
      h, were higher (P < 0.05) and DeltaE was lower (P < 0.05) for fried and L, 
      degrees h were significantly (P < 0.05) higher for baked chips produced from
      ultra-sonication as compare to traditional. Baked chips texture for ultra
      sonication was significantly higher (P < 0.05) on BFG, BPD, PFF, and FD. Fried
      tortilla chips texture were higher significantly (P < 0.05) in BFG and PFF for
      ultra-sonication than traditional processing. However, the instrumental
      differences were not detected in sensory analysis, concluding possibility of
      power ultrasound as potential tortilla chips processing aid. 

PMID- 25939827
TI  - How do people live life successfully with Parkinson's disease?
AB  - AIMS AND OBJECTIVES: The aim of this paper is to explore how people live life
      successfully with Parkinson's disease and what contributed to the level of
      success. OBJECTIVES: To examine the level of success as defined by people with
      Parkinson's disease. To find what contributed to the level of success.
      BACKGROUND: Self-care support has gained importance for supporting people with
      their chronic diseases including Parkinson's disease. Although self-care and life
      adjustments can improve patients' general well-being, it is unclear which
      approaches best facilitate positive adjustments to illness. DESIGN: Semi
      structured interviews with participants with Parkinson's disease. METHODS: Eight
      participants living with Parkinson's disease for 2-16 years were recruited from a
      Parkinson's disease voluntary group in the UK. Interviews covered their perceived
      level of success and the factors which they perceived led to that success.
      Thematic analysis was used to analyse the data. RESULTS: Participants rated a
      high level of success in living with Parkinson's disease with an average personal
      rating 75/100 despite facing difficulties. Successful living was perceived to
      have taken place when people were either (1) able to return to their usual state
      of health or (2) considered themselves to be stable within a new/readjusted state
      of health. Aspects which were perceived to support positive psychosocial
      adjustment included a positive mindset, determination, acceptance of new
      challenges and family support. CONCLUSION: Maintaining usual life and physical
      ability is the major concern among the people with Parkinson's disease. It would
      be helpful for health care professionals to identify what constitutes a 'usual'
      life for that person and to support them to develop a positive mindset and
      acceptance of new challenges, drawing on the determination of the person as well
      as any available family support. RELEVANCE TO CLINICAL PRACTICE: In supporting
      self-care, it is helpful to gain information about the subjective experience of
      living with Parkinson's disease including their perceived level of success at the
      time and what led to that perceived success for that person.

PMID- 25939828
TI  - Elderly acute myeloid leukemia: assessing risk.
AB  - Treatment of older adults with acute myeloid leukemia (AML) is challenging in
      part due to the difficulty of accurately predicting risks and benefits of
      available therapies. While older patients represent the majority of those with
      newly diagnosed disease, there remains no consensus regarding optimal therapy.
      Older age is associated with increased risk of treatment-related toxicity and
      worse survival compared to younger adults. Age-related outcome disparity in the
      setting of AML therapy is clearly attributed in part to differences in tumor
      biology conferring resistance to therapy. However, physiologic changes of aging
      that decrease treatment tolerance also influence outcomes and vary among patients
      of the same chronologic age. Measurable patient characteristics such as
      comorbidity and physical function can reflect the heterogeneity of physiologic
      aging among older patients and help predict resilience during and after the
      stress of diagnosis and treatment. To improve outcomes for older adults with AML,
      it will be critical to investigate the predictive utility of patient
      characteristics in parallel with tumor biology to improve decision-making, inform
      trial design, and identify actionable targets for supportive care interventions.
      This review will focus on available data addressing risk assessment for older
      adults treated for AML with a focus on patient characteristics that may reflect
      vulnerability to poor treatment tolerance. 

PMID- 25939829
TI  - Canine distemper virus as a threat to wild tigers in Russia and across their
      range.
AB  - Canine distemper virus (CDV) has recently been identified in populations of wild
      tigers in Russia and India. Tiger populations are generally too small to maintain
      CDV for long periods, but are at risk of infections arising from more abundant
      susceptible hosts that constitute a reservoir of infection. Because CDV is an
      additive mortality factor, it could represent a significant threat to small,
      isolated tiger populations. In Russia, CDV was associated with the deaths of
      tigers in 2004 and 2010, and was coincident with a localized decline of tigers in
      Sikhote-Alin Biosphere Zapovednik (from 25 tigers in 2008 to 9 in 2012). Habitat
      continuity with surrounding areas likely played an important role in promoting an
      ongoing recovery. We recommend steps be taken to assess the presence and the
      impact of CDV in all tiger range states, but should not detract focus away from
      the primary threats to tigers, which include habitat loss and fragmentation,
      poaching and retaliatory killing. Research priorities include: (i) recognition
      and diagnosis of clinical cases of CDV in tigers when they occur; and (ii)
      collection of baseline data on the health of wild tigers. CDV infection of
      individual tigers need not imply a conservation threat, and modeling should
      complement disease surveillance and targeted research to assess the potential
      impact to tiger populations across the range of ecosystems, population densities
      and climate extremes occupied by tigers. Describing the role of domestic and wild
      carnivores as contributors to a local CDV reservoir is an important precursor to
      considering control measures. 

PMID- 25939830
TI  - The All-Alpha Domains of Coupling Proteins from the Agrobacterium tumefaciens
      VirB/VirD4 and Enterococcus faecalis pCF10-Encoded Type IV Secretion Systems
      Confer Specificity to Binding of Cognate DNA Substrates.
AB  - Bacterial type IV coupling proteins (T4CPs) bind and mediate the delivery of DNA
      substrates through associated type IV secretion systems (T4SSs). T4CPs consist of
      a transmembrane domain, a conserved nucleotide-binding domain (NBD), and a
      sequence-variable helical bundle called the all-alpha domain (AAD). In the T4CP
      structural prototype, plasmid R388-encoded TrwB, the NBD assembles as a
      homohexamer resembling RecA and DNA ring helicases, and the AAD, which sits at
      the channel entrance of the homohexamer, is structurally similar to N-terminal
      domain 1 of recombinase XerD. Here, we defined the contributions of AADs from the
      Agrobacterium tumefaciens VirD4 and Enterococcus faecalis PcfC T4CPs to DNA
      substrate binding. AAD deletions abolished DNA transfer, whereas production of
      the AAD in otherwise wild-type donor strains diminished the transfer of cognate
      but not heterologous substrates. Reciprocal swaps of AADs between PcfC and VirD4
      abolished the transfer of cognate DNA substrates, although strikingly, the VirD4
      AADPcfC chimera (VirD4 with the PcfC AAD) supported the transfer of a mobilizable
      plasmid. Purified AADs from both T4CPs bound DNA substrates without sequence
      preference but specifically bound cognate processing proteins required for
      cleavage at origin-of-transfer sequences. The soluble domains of VirD4 and PcfC
      lacking their AADs neither exerted negative dominance in vivo nor specifically
      bound cognate processing proteins in vitro. Our findings support a model in which
      the T4CP AADs contribute to DNA substrate selection through binding of associated
      processing proteins. Furthermore, MOBQ plasmids have evolved a docking mechanism
      that bypasses the AAD substrate discrimination checkpoint, which might account
      for their capacity to promiscuously transfer through many different T4SSs.
      IMPORTANCE: For conjugative transfer of mobile DNA elements, members of the
      VirD4/TraG/TrwB receptor superfamily bind cognate DNA substrates through
      mechanisms that are largely undefined. Here, we supply genetic and biochemical
      evidence that a helical bundle, designated the all-alpha domain (AAD), of T4SS
      receptors functions as a substrate specificity determinant. We show that AADs
      from two substrate receptors, Agrobacterium tumefaciens VirD4 and Enterococcus
      faecalis PcfC, bind DNA without sequence or strand preference but specifically
      bind the cognate relaxases responsible for nicking and piloting the transferred
      strand through the T4SS. We propose that interactions of receptor AADs with DNA
      processing factors constitute a basis for selective coupling of mobile DNA
      elements with type IV secretion channels.

PMID- 25939831
TI  - Intraspecies Competition in Serratia marcescens Is Mediated by Type VI-Secreted
      Rhs Effectors and a Conserved Effector-Associated Accessory Protein.
AB  - The type VI secretion system (T6SS) is widespread in Gram-negative bacteria and
      can deliver toxic effector proteins into eukaryotic cells or competitor bacteria.
      Antibacterial T6SSs are increasingly recognized as key mediators of
      interbacterial competition and may contribute to the outcome of many
      polymicrobial infections. Multiple antibacterial effectors can be delivered by
      these systems, with diverse activities against target cells and distinct modes of
      secretion. Polymorphic toxins containing Rhs repeat domains represent a recently
      identified and as-yet poorly characterized class of T6SS-dependent effectors.
      Previous work had revealed that the potent antibacterial T6SS of the
      opportunistic pathogen Serratia marcescens promotes intraspecies as well as
      interspecies competition (S. L. Murdoch, K. Trunk, G. English, M. J. Fritsch, E.
      Pourkarimi, and S. J. Coulthurst, J Bacteriol 193:6057-6069, 2011,
      http://dx.doi.org/10.1128/JB.05671-11). In this study, two new Rhs family
      antibacterial effectors delivered by this T6SS have been identified. One of these
      was shown to act as a DNase toxin, while the other contains a novel, cytoplasmic
      acting toxin domain. Importantly, using S. marcescens, it has been demonstrated
      for the first time that Rhs proteins, rather than other T6SS-secreted effectors,
      can be the primary determinant of intraspecies competition. Furthermore, a new
      family of accessory proteins associated with T6SS effectors has been identified,
      exemplified by S. marcescens EagR1, which is specifically required for deployment
      of its associated Rhs effector. Together, these findings provide new insight into
      how bacteria can use the T6SS to deploy Rhs-family effectors and mediate
      different types of interbacterial interactions. IMPORTANCE: Infectious diseases
      caused by bacterial pathogens represent a continuing threat to health and
      economic prosperity. To counter this threat, we must understand how such
      organisms survive and prosper. The type VI secretion system is a weapon that many
      pathogens deploy to compete against rival bacterial cells by injecting multiple
      antibacterial toxins into them. The ability to compete is vital considering that
      bacteria generally live in mixed communities. We aimed to identify new toxins and
      understand their deployment and role in interbacterial competition. We describe
      two new type VI secretion system-delivered toxins of the Rhs class, demonstrate
      that this class can play a primary role in competition between closely related
      bacteria, and identify a new accessory factor needed for their delivery.

PMID- 25939832
TI  - Replication Restart after Replication-Transcription Conflicts Requires RecA in
      Bacillus subtilis.
AB  - Efficient duplication of genomes depends on reactivation of replication forks
      outside the origin. Replication restart can be facilitated by recombination
      proteins, especially if single- or double-strand breaks form in the DNA. Each
      type of DNA break is processed by a distinct pathway, though both depend on the
      RecA protein. One common obstacle that can stall forks, potentially leading to
      breaks in the DNA, is transcription. Though replication stalling by transcription
      is prevalent, the nature of DNA breaks and the prerequisites for replication
      restart in response to these encounters remain unknown. Here, we used an
      engineered site-specific replication-transcription conflict to identify and
      dissect the pathways required for the resolution and restart of replication forks
      stalled by transcription in Bacillus subtilis. We found that RecA, its loader
      proteins RecO and AddAB, and the Holliday junction resolvase RecU are required
      for efficient survival and replication restart after conflicts with
      transcription. Genetic analyses showed that RecO and AddAB act in parallel to
      facilitate RecA loading at the site of the conflict but that they can each
      partially compensate for the other's absence. Finally, we found that RecA and
      either RecO or AddAB are required for the replication restart and helicase loader
      protein, DnaD, to associate with the engineered conflict region. These results
      suggest that conflicts can lead to both single-strand gaps and double-strand
      breaks in the DNA and that RecA loading and Holliday junction resolution are
      required for replication restart at regions of replication-transcription
      conflicts. IMPORTANCE: Head-on conflicts between replication and transcription
      occur when a gene is expressed from the lagging strand. These encounters stall
      the replisome and potentially break the DNA. We investigated the necessary
      mechanisms for Bacillus subtilis cells to overcome a site-specific engineered
      conflict with transcription of a protein-coding gene. We found that the
      recombination proteins RecO and AddAB both load RecA onto the DNA in response to
      the head-on conflict. Additionally, RecA loading by one of the two pathways was
      required for both replication restart and efficient survival of the collision.
      Our findings suggest that both single-strand gaps and double-strand DNA breaks
      occur at head-on conflict regions and demonstrate a requirement for recombination
      to restart replication after collisions with transcription.

PMID- 25939835
TI  - Introduction.

PMID- 25939833
TI  - Characterization of the Dynamic Germination of Individual Clostridium difficile
      Spores Using Raman Spectroscopy and Differential Interference Contrast
      Microscopy.
AB  - The Gram-positive spore-forming anaerobe Clostridium difficile is a leading cause
      of nosocomial diarrhea. Spores of C. difficile initiate infection when triggered
      to germinate by bile salts in the gastrointestinal tract. We analyzed germination
      kinetics of individual C. difficile spores using Raman spectroscopy and
      differential interference contrast (DIC) microscopy. Similar to Bacillus spores,
      individual C. difficile spores germinating with taurocholate plus glycine began
      slow leakage of a ~15% concentration of a chelate of Ca(2+) and dipicolinic acid
      (CaDPA) at a heterogeneous time T1, rapidly released CaDPA at Tlag, completed
      CaDPA release at Trelease, and finished peptidoglycan cortex hydrolysis at
      Tlysis. T1 and Tlag values for individual spores were heterogeneous, but
      DeltaTrelease periods (Trelease - Tlag) were relatively constant. In contrast to
      Bacillus spores, heat treatment did not stimulate spore germination in the two C.
      difficile strains tested. C. difficile spores did not germinate with taurocholate
      or glycine alone, and different bile salts differentially promoted spore
      germination, with taurocholate and taurodeoxycholate being best. Transient
      exposure of spores to taurocholate plus glycine was sufficient to commit
      individual spores to germinate. C. difficile spores did not germinate with CaDPA,
      in contrast to B. subtilis and C. perfringens spores. However, the detergent
      dodecylamine induced C. difficile spore germination, and rates were increased by
      spore coat removal although cortex hydrolysis did not follow Trelease, in
      contrast with B. subtilis. C. difficile spores lacking the cortex-lytic enzyme,
      SleC, germinated extremely poorly, and cortex hydrolysis was not observed in the
      few sleC spores that partially germinated. Overall, these findings indicate that
      C. difficile and B. subtilis spore germination exhibit key differences.
      IMPORTANCE: Spores of the Gram-positive anaerobe Clostridium difficile are
      responsible for initiating infection by this important nosocomial pathogen. When
      exposed to germinants such as bile salts, C. difficile spores return to life
      through germination in the gastrointestinal tract and cause disease, but their
      germination has been studied only with population-wide measurements. In this work
      we used Raman spectroscopy and DIC microscopy to monitor the kinetics of
      germination of individual C. difficile spores, the commitment of spores to
      germination, and the effect of germinant type and concentration, sublethal heat
      shock, and spore decoating on germination. Our data suggest that the order of
      germination events in C. difficile spores differs from that in Bacillus spores
      and provide new insights into C. difficile spore germination.

PMID- 25939834
TI  - Novel Transcriptional Regulons for Autotrophic Cycle Genes in Crenarchaeota.
AB  - Autotrophic microorganisms are able to utilize carbon dioxide as their only
      carbon source, or, alternatively, many of them can grow heterotrophically on
      organics. Different variants of autotrophic pathways have been identified in
      various lineages of the phylum Crenarchaeota. Aerobic members of the order
      Sulfolobales utilize the hydroxypropionate-hydroxybutyrate cycle (HHC) to fix
      inorganic carbon, whereas anaerobic Thermoproteales use the dicarboxylate
      hydroxybutyrate cycle (DHC). Knowledge of transcriptional regulation of
      autotrophic pathways in Archaea is limited. We applied a comparative genomics
      approach to predict novel autotrophic regulons in the Crenarchaeota. We report
      identification of two novel DNA motifs associated with the autotrophic pathway
      genes in the Sulfolobales (HHC box) and Thermoproteales (DHC box). Based on
      genome context evidence, the HHC box regulon was attributed to a novel
      transcription factor from the TrmB family named HhcR. Orthologs of HhcR are
      present in all Sulfolobales genomes but were not found in other lineages. A
      predicted HHC box regulatory motif was confirmed by in vitro binding assays with
      the recombinant HhcR protein from Metallosphaera yellowstonensis. For the DHC box
      regulon, we assigned a different potential regulator, named DhcR, which is
      restricted to the order Thermoproteales. DhcR in Thermoproteus neutrophilus
      (Tneu_0751) was previously identified as a DNA-binding protein with high affinity
      for the promoter regions of two autotrophic operons. The global HhcR and DhcR
      regulons reconstructed by comparative genomics were reconciled with available
      omics data in Metallosphaera and Thermoproteus spp. The identified regulons
      constitute two novel mechanisms for transcriptional control of autotrophic
      pathways in the Crenarchaeota. IMPORTANCE: Little is known about transcriptional
      regulation of carbon dioxide fixation pathways in Archaea. We previously applied
      the comparative genomics approach for reconstruction of DtxR family regulons in
      diverse lineages of Archaea. Here, we utilize similar computational approaches to
      identify novel regulatory motifs for genes that are autotrophically induced in
      microorganisms from two lineages of Crenarchaeota and to reconstruct the
      respective regulons. The predicted novel regulons in archaeal genomes control the
      majority of autotrophic pathway genes and also other carbon and energy metabolism
      genes. The HhcR regulon was experimentally validated by DNA-binding assays in
      Metallosphaera spp. Novel regulons described for the first time in this work
      provide a basis for understanding the mechanisms of transcriptional regulation of
      autotrophic pathways in Archaea.

PMID- 25939836
TI  - Management of the failing Fontan.
AB  - With and increasing number of early survivors after the palliation of the single
      ventricle physiology there is a burgeoning Fontan population worldwide that will
      pose unique challenges because of the inevitable sequelae related to the absence
      of the alleged "needless" sub-pulmonic ventricle. The increasing number and older
      age single-ventricle patients highlights the results of successful contemporary
      surgical palliation in children, leading to the development of an adult single
      ventricle population with unpredictable socio-economic and health service
      impacts. The wide variability in clinical status of patients with Fontan
      circulation reflects not only the broadened spectrum of morphological substrates
      involved, but also the evolving surgical techniques during the last four decades.
      This has come in the wake of a gradual understanding of an incredibly tricky
      physiology. The magnitude of the disease, the physio-pathological mechanisms, and
      the therapeutic options to optimize the "failing Fontan" status and to delay the
      irreversible deterioration of "Fontan failure" condition are discussed in this
      review. 

PMID- 25939838
TI  - Mechanical circulatory support in univentricular hearts: current management.
AB  - Failing single-ventricle patients have now come into focus as the next cohort
      where improvement in outcomes for mechanical circulatory support can be realized.
      There is a paucity of published patient reports or management protocols in this
      patient population. Increased interest exists in finding answers of how to bridge
      these patients to transplant. We review the current literature and describe our
      approach to the patient with univentricular heart needing mechanical circulatory
      support. 

PMID- 25939837
TI  - Transplantation in the Fontan patient.
AB  - The failing Fontan circulation presents difficult treatment challenges. When
      Fontan revision and or intervention for treatable arrhythmias is not feasible,
      heart transplantation is the only therapeutic option. Particular challenges
      presented by these patients include limited ability to assess hemodynamics,
      complex anatomy, multiple prior procedures, and unique underlying pathologic
      states. These issues complicate the decision-making process for further surgical
      intervention verses transplantation. The pre-transplant evaluation, transplant
      operation, and post-operative management are more problematic for these patients
      compared with most patients undergoing transplantation. Consequently, failing
      Fontan patients constitute one of the highest risk heart transplant subsets. 

PMID- 25939839
TI  - Evolution of the surgical approach to congenitally corrected transposition of the
      great arteries.
AB  - The traditional surgical approach (physiologic repair) of congenitally corrected
      transposition of the great arteries (ccTGA) attempts at restoring normal
      physiology by repairing the associated lesions. It fails to address the most
      serious anatomic abnormality, mainly ventriculoarterial discordance, and results
      in less than optimal long-term outcomes. Anatomic repair was introduced to
      incorporate the left ventricle into the systemic circulation. The excellent short
      term and intermediate results of the double switch operation and its
      modifications make it the procedure of choice for the treatment of ccTGA. 

PMID- 25939840
TI  - Root translocation in congenitally corrected transposition of the great arteries
      with ventricular septal defect and pulmonary stenosis, and other lesions.
AB  - The pulmonary root translocation (PRT) procedure has been used to correct
      ventriculoarterial discordance or malposition of great arteries since 1994. It
      was part of the surgical repair of 62 consecutive patients presenting with
      congenitally corrected transposition of the great arteries (CCTGA) with
      ventricular septal defect (VSD) and pulmonary stenosis (PS), or other complex
      congenital heart disease with malposition of the great arteries, VSD, and PS. PRT
      was performed as follows: removal of the pulmonary artery (PA) with the pulmonary
      valve from its abnormal position, closure of the consequent hole with an
      autologous pericardial patch, resection of some conal septum, creation of an
      intraventricular tunnel connecting the left ventricle to the aorta, and
      construction of a new right ventricular outflow tract using the translocated PA.
      In patients presenting with important pulmonary valve stenosis, the pulmonary
      artery was enlarged with a monocusp valve pericardial patch. The Senning
      procedure was used with some modification to complete the anatomical repair in
      CCTGA patients. Overall in-hospital and long-term mortality were 4.8% and 3.4%,
      respectively. PRT appears to be a good surgical alternative for patients
      presenting with CCTGA with VSD and PS, and other lesions involving malposition of
      the great arteries, VSD, and PS. 

PMID- 25939841
TI  - Left ventricular retraining: theory and practice.
AB  - Congenitally corrected transposition of the great arteries or l-transposition of
      the great arteries is characterized by discordance of both the atrioventricular
      and ventriculoarterial connections. Physiologic repair of associated conditions,
      whereby the morphologic right ventricle remains the systemic ventricle, has
      resulted in unsatisfactory long-term outcomes due to the development of right
      ventricular failure and tricuspid valve regurgitation. While intuitively
      attractive, anatomic repair also has inherent challenges and risks, particularly
      for those patients who present late and require left ventricular retraining.
      Although early and intermediate-term outcomes for anatomic repair have been
      encouraging, longer-term follow-up has demonstrated concern for late left
      ventricular dysfunction in this subgroup of patients. Continued monitoring of
      this challenging patient population will clarify late outcomes and inform
      clinical management in the future. 

PMID- 25939842
TI  - Checklists and safety in pediatric cardiac surgery.
AB  - In rebuilding Tulane's pediatric heart center after Hurricane Katrina, the use of
      checklists proved to be essential, not only in rebuilding inventory and systems,
      but the culture of continued debriefing around their use was seminal in
      establishing a culture of safety and trust between caregivers; safety that
      ultimately benefitted our patients. 

PMID- 25939843
TI  - Improving pacemaker therapy in congenital heart disease: contractility and
      resynchronization.
AB  - Designed as effective therapy for patients with symptomatic bradycardia,
      implantable cardiac pacemakers initially served to improve symptoms and survival.
      With initial applications to the elderly and those with severe myocardial
      disease, extended longevity was not a major concern. However, with design
      technology advances in leads and generators since the 1980s, pacemaker therapy is
      now readily applicable to all age patients, including children with congenital
      heart defects. As a result, emphasis and clinical interests have advanced beyond
      simply quantity to quality of life. Adverse cardiac effects of pacing from right
      ventricular apical or epicardial sites with resultant left bundle branch QRS
      configurations have been recognized. As a result, and with the introduction of
      newer catheter-delivered pacing leads, more recent studies have focused on
      alternative or select pacing sites such as septal, outflow tract, and para-bundle
      of His. This is especially important in dealing with pacemaker therapy among
      younger patients and those with congenital heart disease, with expected decades
      of artificial cardiac stimulation, in which adverse myocellular changes secondary
      to pacing itself have been reported. As a correlate to these alternate or select
      pacing sites, applications of left ventricular pacing, either via the coronary
      sinus, intraseptal or epicardial, alone or in combination with right ventricular
      pacing, have gained interest for patients with heart failure. Although cardiac
      resynchronization pacing has, to date, had limited clinical applications among
      patients with congenital heart disease, the few published reports do indicate
      potential benefits as a bridge to cardiac transplant. 

PMID- 25939844
TI  - Tracheobronchial issues in congenital heart disease.
AB  - In children with congenital heart disease, tracheobronchial compromise is
      uncommon but potentially life-threatening. Airway lesions in these patients may
      be congenital or acquired, and may be stenotic, compressive, or malacic in
      nature. We present an overview of the etiologies of tracheobronchial lesions
      typically seen in children with congenital heart disease and review management
      options for these lesions. 

PMID- 25939845
TI  - Three-dimensional echocardiography for the assessment of atrioventricular valves
      in congenital heart disease: past, present and future.
AB  - Echocardiography has developed as an imaging technology over 60 years to become
      the mainstay for investigating heart disease, providing invaluable structural and
      functional information. In the last 20 years, 3-dimensional echocardiography
      (3DE) has emerged as an adjunct to 2-dimensional echocardiography in adult and
      congenital heart disease. Early work with 3-dimensional imaging of the mitral
      valve describing normal annular shape and function significantly changed the
      understanding of mitral valve dynamics. Further work led to our current
      understanding of the mitral valve working as a unit, with all components vital to
      its normal function. With improving technology and ease of use, similar 3DE
      techniques have been used in congenital heart disease to study the unique anatomy
      and function of atrioventricular (AV) valves, specifically the tricuspid valve in
      hypoplastic left heart syndrome, and the left AV valve in atrioventricular septal
      defects. This paper describes the role of 3DE in assessing AV valve function in
      normal valves, and in congenital heart disease. 

PMID- 25939846
TI  - Best practices for health and safety technology transfer in construction.
AB  - BACKGROUND: Construction continues to be a dangerous industry, yet solutions that
      would prevent injury and illness do exist. Prevention of injury and illness among
      construction workers requires dissemination, adoption, and implementation of
      these effective interventions, or "research to practice" (r2p). METHODS: CPWR
      recruited participants with experience and insight into effective methods for
      diffusion of health and safety technologies in this industry for a symposium with
      3 group sessions and 3 breakout groups. The organizers reviewed session notes and
      identified 141 recommendations, which were then assigned to 13 over-arching
      themes. RESULTS: Recommendations included a guide for researchers on patenting
      and licensing, a business case model, and in-depth case studies including
      development, testing, manufacturing, marketing, and diffusion. CONCLUSIONS: A
      more comprehensive understanding of the health and safety technology transfer
      landscape, the various actors, and their motivators and goals will help to foster
      the successful commercialization and diffusion of health and safety innovations.

PMID- 25939847
TI  - Association of common variants on chromosome 8q24 with gastric cancer in
      Venezuelan patients.
AB  - Gastric cancer remains one of the leading causes of death in the world, being
      Central and South America among the regions showing the highest incidence and
      mortality rates worldwide. Although several single nucleotide polymorphisms
      (SNPs) identified in the chromosomal region 8q24 by genome-wide association
      studies have been related with the risk of different kinds of cancers, their role
      in the susceptibility of gastric cancer in Latin American populations has not
      been evaluated yet. Hereby, we performed a case-control study to explore the
      associations between three SNPs at 8q24 and gastric cancer risk in Venezuelan
      patients. We analyzed rs1447295, rs4733616 and rs6983267 SNPs in 122 paraffin
      embedded tumor samples from archival bank and 129 samples with chronic gastritis
      (obtained by upper endoscopy during the study) from the Central Hospital of
      Barquisimeto (Lara, Venezuela). Genotypes were determined by PCR-RFLP reactions
      designed in this study for efficient genotyping of formalin-fixed/paraffin
      embedded tissues. No significant differences in genotype frequencies between case
      and control groups were found. However, carriers of the homozygous TT genotype of
      SNP rs4733616 had an increased risk of developing poorly differentiated gastric
      cancer according to the codominant (OR=3.59, P=0.035) and the recessive models
      (OR=4.32, P=0.014, best-fitting model of inheritance), adjusted by age and
      gender. Our study suggests that the SNP rs4733616 is associated with
      susceptibility to poorly differentiated gastric cancer in Venezuelans. Additional
      studies are needed to further interrogate the prognostic value of the rs4733616
      marker in this high-risk population for gastric cancer.

PMID- 25939848
TI  - Identifying a potential receptor for the antibacterial peptide of sponge Axinella
      donnani endosymbiont.
AB  - Marine sponges and their associated bacteria are rich sources of novel secondary
      metabolites with therapeutic usefulness. In our earlier work, we have identified
      a novel antibacterial peptide from the marine sponge Axinella donnani
      endosymbiotic bacteria. In this work, we have carried out a comparative genomic
      analysis and identified a set of 60 proteins as probable receptor which is common
      in all the strains. The analysis on binding substrate showed that beta barrel
      assembly machinery (BamA) of the outer membrane protein 85 (omp85) superfamily is
      a potential receptor protein for the antibacterial peptide. It plays a central
      role in OMP biogenesis, especially in cell viability. Further, the triplet and
      quartet motifs RGF and YGDG, respectively in L6 loop are conserved over all the
      strains and these conserved residues interact with antibacterial peptide to
      inhibit the BamA function, which is essential for OMP biogenesis. 

PMID- 25939849
TI  - Mid-Term Results of Congenital Supravalvar Mitral Ring Resection.
AB  - BACKGROUND: Supravalvar mitral ring is a rare congenital anomaly leading to left
      ventricle inflow obstruction. We present our surgical experience and mid-term
      results in patients operated for supravalvar mitral ring and associated
      congenital heart defects. MATERIALS AND METHODS: A retrospective analysis was
      performed in order to evaluate the cases surgically treated with the diagnosis of
      supravalvar mitral ring between 2001 and 2014. Ten patients were identified,
      seven of whom had accompanying congenital heart defects. Median age at the
      operation was 4.5 years. RESULTS: Ventricular septal defects were encountered in
      half of the cases. Two of the patients had mitral annular hypoplasia, another two
      had the components of Shone's complex. The mean preoperative gradient across the
      supravalvar mitral ring decreased from 14.1 +/- 4.2 mmHg to 4.6 +/- 2.2 mmHg. All
      patients are alive and remain in a good clinical condition after a mean follow-up
      of five years. CONCLUSION: Supravalvar mitral ring is a surgically treatable
      cause of left ventricular inflow obstruction. Although residual gradients may be
      encountered in patients with mitral annular hypoplasia, surgical resection of the
      ring is encouraged.

PMID- 25939850
TI  - Education and endorsement in infant mental health.

PMID- 25939851
TI  - Nanoparticle-coated micro-optofluidic ring resonator as a detector for microscale
      gas chromatographic vapor analysis.
AB  - A vapor sensor comprising a nanoparticle-coated microfabricated optofluidic ring
      resonator (MUOFRR) is introduced. A multilayer film of polyether functionalized,
      thiolate-monolayer-protected gold nanoparticles (MPN) was solvent cast on the
      inner wall of the hollow cylindrical SiOxMUOFRR resonator structure, and
      whispering gallery mode (WGM) resonances were generated with a 1550 nm tunable
      laser via an optical fiber taper. Reversible shifts in the WGM resonant
      wavelength upon vapor exposure were detected with a photodetector. The MUOFRR
      chip was connected to a pair of upstream etched-Si chips containing PDMS-coated
      separation MUcolumns and calibration curves were generated from the peak-area
      responses to five volatile organic compounds (VOCs). Calibration curves were
      linear, and the sensitivities reflected the influence of analyte volatility and
      analyte-MPN functional group affinity. Sorption-induced changes in film thickness
      apparently dominate over changes in the refractive index of the film as the
      determinant of responses for all VOCs. Peaks from the MPN-coated MUOFRR were just
      20-50% wider than those from a flame ionization detector for similar MUcolumn
      separation conditions, reflecting the rapid response of the sensor for VOCs. The
      five VOCs were baseline separated in <1.67 min, with detection limits as low as
      38 ng. 

PMID- 25939853
TI  - Wearing complete dentures is associated with changes in the three-dimensional
      shape of the oropharynx in edentulous older people that affect swallowing.
AB  - OBJECTIVE: To investigate the effects of wearing complete dentures on pharyngeal
      shape for swallowing in edentulous older people. BACKGROUND: In the absence of
      complete dentures, edentulous older people often lose the occlusal support
      necessary to position the mandible, which leads to an anterosuperior shift of the
      mandible during swallowing. This may result in pharyngeal shape changes effecting
      swallowing function in older people. However, the details of this phenomenon are
      currently unclear. MATERIALS AND METHODS: Participants were 17 older edentulous
      volunteers. Cone-beam computed tomography imaging was performed with the
      participant in the seated position and wearing (i) both maxillary and mandibular
      dentures, (ii) maxillary dentures only and (iii) no dentures. During imaging,
      participants were instructed to keep their mouth closed to the mandibular
      position determined in advance during swallowing for each denture-wearing
      condition. The volume, height and average cross-sectional area of the velopharynx
      and oropharynx were measured, and the positions of the epiglottis and mandible
      were recorded. RESULTS: While the vertical height of the oral cavity and pharynx
      significantly decreased, the volume and average cross-sectional area of the
      oropharynx significantly increased when dentures were not worn (p < 0.01). The
      absence of dentures caused an anterosuperior shift of the mandible when
      swallowing and drew the epiglottis forward, resulting in expansion of the
      oropharynx where the tongue base forms the anterior wall. CONCLUSION: The absence
      of dentures results in anatomical changes in oropharyngeal shape that may
      exacerbate the pharyngeal expansion caused by ageing and reduce the swallowing
      reserve.

PMID- 25939852
TI  - A relA-dependent regulatory cascade for auto-induction of microbisporicin
      production in Microbispora corallina.
AB  - Microbisporicin is a potent type I lantibiotic produced by the rare actinomycete
      Microbispora corallina that is in preclinical trials for the treatment of
      infections caused by methicillin-resistant isolates of Staphylococcus aureus
      (MRSA). Analysis of the gene cluster for the biosynthesis of microbisporicin,
      which contains two unique post-translationally modified residues (5
      chlorotryptophan and 3, 4-dihydroxyproline), has revealed an unusual regulatory
      mechanism that involves a pathway-specific extracytoplasmic function sigma factor
      (MibX)/anti-sigma factor (MibW) complex and an additional transcriptional
      regulator MibR. A model for the regulation of microbisporicin biosynthesis
      derived from transcriptional, mutational and quantitative reverse transcription
      polymerase chain reaction analyses suggests that MibR, which contains a C
      terminal DNA-binding domain found in the LuxR family of transcriptional
      activators, functions as an essential master regulator to trigger microbisporicin
      production while MibX and MibW induce feed-forward biosynthesis and producer
      immunity. Moreover, we demonstrate that initial expression of mibR, and thus
      microbisporicin production, is dependent on the ppGpp synthetase gene (relA) of
      M. corallina. In addition, we show that constitutive expression of either of the
      two positively acting regulatory genes, mibR or mibX, leads to precocious and
      enhanced microbisporicin production. 

PMID- 25939854
TI  - Circadian clock regulation of melatonin MTNR1B receptor expression in human
      myometrial smooth muscle cells.
AB  - Circadian genes are expressed in virtually all cells and tissues, and circadian
      rhythms influence many bodily processes, including reproductive physiology. The
      expression of hMTNR1B is suppressed during pregnancy until late in term (much
      like the oxytocin receptor), at which time it is up-regulated to allow for the
      nocturnal melatonin/oxytocin synergy, which promotes strong nocturnal
      contractions. Little is currently known about the regulation of hMNTR1b, nor
      about its functional significance in the myometrium. We, therefore, aimed to
      elucidate some of the transcription factors that regulate hMNTR1b gene expression
      in the human myometrium and to determine if hMNTR1b is under circadian control.
      In this study, we used immortalized and primary myometrial cells that were
      assessed for circadian gene expression rhythms using real-time bioluminometry and
      quantitative PCR. Chromatin immunoprecipitation examined the binding of the clock
      gene product brain and muscle aryl hydrocarbon receptor nuclear translocator
      (ARNT)-like protein 1 (BMAL1) to the promoter of the hMTNR1B gene. Overexpression
      studies tested the role of circadian locomotor output cycles kaput (CLOCK) and
      its partner BMAL1 in regulating hMTNR1B expression. We confirmed circadian clock
      gene expression in both immortalized human myometrial cells and primary
      myometrial cell cultures. We further showed that the hBMAL1 protein binds to an E
      box motif in the proximal promoter of the hMTNR1B gene. Overexpression studies
      demonstrated that the BMAL1/CLOCK complex activates expression of hMTNR1B leading
      to a circadian rhythm in phase with the E-box driven clock gene hPER2 (Period 2).
      These results indicate, for the first time, the presence of a functional
      circadian clock in the human myometrium with the hMTNR1B gene as a clock
      controlled target. Further investigations could open new vistas for understanding
      the regulation of uterine contractions and the timing of human labor. 

PMID- 25939855
TI  - Cooking-related PM2.5 and acrolein measured in grocery stores and comparison with
      other retail types.
AB  - We measured particulate matter (PM), acrolein, and other indoor air contaminants
      in eight visits to grocery stores in California. Retail stores of other types
      (hardware, furniture, and apparel) were also sampled on additional visits. Based
      on tracer gas decay data, most stores had adequate ventilation according to
      minimum ventilation rate standards. Grocery stores had significantly higher
      concentrations of acrolein, fine and ultrafine PM, compared to other retail
      stores, likely attributable to cooking. Indoor concentrations of PM2.5 and
      acrolein exceeded health guidelines in all tested grocery stores. Acrolein
      emission rates to indoors in grocery stores had a mean estimate about 30 times
      higher than in other retail store types. About 80% of the indoor PM2.5 measured
      in grocery stores was emitted indoors, compared to only 20% for the other retail
      store types. Calculations suggest a substantial increase in outdoor air
      ventilation rate by a factor of three from current level is needed to reduce
      indoor acrolein concentrations. Alternatively, acrolein emission to indoors needs
      to be reduced 70% by better capturing of cooking exhaust. To maintain indoor
      PM2.5 below the California annual ambient standard of 12 MUg/m(3) , grocery
      stores need to use air filters with an efficiency rating higher than the MERV 8
      air filters commonly used today.

PMID- 25939856
TI  - Monetising the provision of informal long-term care by elderly people: estimates
      for European out-of-home caregivers based on the well-being valuation method.
AB  - Providing informal care can be both a burden and a source of satisfaction. To
      understand the welfare effect on caregivers, we need an estimate of the 'shadow
      value' of informal care, an imputed value for the non-market activity. We use
      data from the 2006-2007 Survey of Health Ageing and Retirement in Europe which
      offers the needed details on 29,471 individuals in Austria, Belgium, the Czech
      Republic, Denmark, France, Germany, Italy, the Netherlands, Poland, Spain, Sweden
      and Switzerland. Of these, 9768 are unpaid non-co-resident caregivers. To
      estimate net costs, we follow the subjective well-being valuation method,
      modelling respondents' life satisfaction as a product of informal care provision,
      income and personal characteristics, then expressing the relation between
      satisfaction and care as a monetary amount. We estimate a positive net effect of
      providing mode rate amounts of informal care, equivalent to ?93 for an hour of
      care/week provided by a caregiver at the median income. The net effect appears to
      turn negative for greater high care burdens (over 30 hours/week). Interestingly,
      the effects of differences in care situation are at least an order of magnitude
      larger. We find that carers providing personal care are significantly more
      satisfied than those primarily giving help with housework, a difference
      equivalent to ?811 a year at the median income. The article makes two unique
      contributions to knowledge. The first is its quantifying a net benefit to
      moderately time-intensive out-of-home caregivers. The second is its clear
      demonstration of the importance of heterogeneity of care burden on different
      subgroups. Care-giving context and specific activities matter greatly, pointing
      to the need for further work on targeting interventions at those caregivers most
      in need of them.

PMID- 25939857
TI  - Characteristics of suspended solids affect bifenthrin toxicity to the calanoid
      copepods Eurytemora affinis and Pseudodiaptomus forbesi.
AB  - Bifenthrin is a pyrethroid pesticide that is highly toxic to aquatic
      invertebrates. The dissolved concentration is generally thought to be the best
      predictor of acute toxicity. However, for the filter-feeding calanoid copepods
      Eurytemora affinis and Pseudodiaptomus forbesi, ingestion of pesticide-bound
      particles could prove to be another route of exposure. The present study
      investigated bifenthrin toxicity to E. affinis and P. forbesi in the presence of
      suspended solids from municipal wastewater effluent and surface water of the San
      Francisco (CA, USA) Estuary. Suspended solids mitigated the toxicity of total
      bifenthrin to E. affinis and P. forbesi, but mortality was higher than what would
      be predicted from dissolved concentrations alone. The results indicate that the
      toxicity and bioavailability of particle-associated bifenthrin was significantly
      correlated with counts of 0.5-um to 2-um particle sizes. Potential explanations
      could include direct ingestion of bifenthrin-bound particles, changes in food
      consumption and feeding behavior, and physical contact with small particles. The
      complex interactions between pesticides and particles of different types and
      sizes demonstrate a need for future ecotoxicological studies to investigate the
      role of particle sizes on aquatic organisms.

PMID- 25939858
TI  - Stiffness and evolution of interfacial micropancakes revealed by AFM quantitative
      nanomechanical imaging.
AB  - Micropancakes are quasi-two-dimensional micron-sized domains on crystalline
      substrates (e.g. highly oriented pyrolytic graphite (HOPG)) immersed in water.
      They are only a few nanometers thick, and are suspected to come from the
      accumulation of dissolved air at the solid-water interface. However, the exact
      chemical nature and basic physical properties of micropancakes have been under
      debate ever since their first observation, primarily due to the lack of a
      suitable characterization technique. In this study, the stiffness of
      micropancakes at the interface between HOPG and ethanol-water solutions was
      investigated by using PeakForce Quantitative NanoMechanics (PF-QNM) mode Atomic
      Force Microscopy (AFM). Our measurements showed that micropancakes were stiffer
      than nanobubbles, and for bilayer micropancakes, the bottom layer in contact with
      the substrate was stiffer than the top one. Interestingly, the micropancakes
      became smaller and softer with an increase in the ethanol concentration in the
      solution, and were undetectable by AFM above a critical concentration of ethanol.
      But they re-appeared after the ethanol concentration in the solution was reduced.
      Clearly the evolution and stiffness of the micropancakes were dependent on the
      chemical composition in the solution, which could be attributed to the
      correlation of the mechanical properties of the micropancakes with the surface
      tension of the liquid phase. Based on the "go-and-come" behaviors of
      micropancakes with the ethanol concentration, we found that the micropancakes
      could actually tolerate the ethanol concentration much higher than 5%, a value
      reported in the literature. The results from this work may be helpful in alluding
      the chemical nature of micropancakes. 

PMID- 25939859
TI  - Serum cytokeratin-18 fragment levels predict development of type 2 diabetes
      mellitus in adult patients with NAFLD.

PMID- 25939860
TI  - Risk of metastasis among rib abnormalities on bone scans in breast cancer
      patients.
AB  - Bone scan abnormalities, especially rib lesions, are often confusing for
      physicians due to a high number of false-positive lesions. This study
      investigated risk factors that are associated with bone metastasis in 613 breast
      cancer patients with bone scan abnormalities. Significantly increased rates of
      bone metastasis were observed in patients with multiple lesions, large tumor
      sizes, and lymph node involvement. In addition, patients with concurrent lesions
      of rib and other sites exhibited a significant higher rate of metastatic disease
      compared to those with other site lesions (P = 0.009). In the subset of 324
      patients with rib abnormalities, the rate of metastasis was extremely low in
      patients with pure rib lesions (1.2%; 95% CI: 0.1%-4.1%). Concurrent lesions of
      rib and other sites were more likely to be rib metastasis compared to pure rib
      lesions (P < 0.001). Moreover, multiple rib lesions and lesions located on
      bilateral ribs were more likely to be rib metastasis (P < 0.001). Our data
      suggest that patients with pure rib abnormalities could be recommended for follow
      up only. However, if concurrent lesions of rib and other sites were detected on
      bone scans, additional radiological examinations should be performed to patients.

PMID- 25939861
TI  - Efficient one-pot synthesis of trans-Pt(II)(salicylaldimine)(4-picoline)Cl
      complexes: effective agents for enhanced expression of p53 tumor suppressor
      genes.
AB  - A series of trans-Pt(II)(salicylaldimine)(4-picoline)Cl complexes were
      synthesized in 78-87% yield using a one-pot procedure from commercially available
      precursors. The structures of these complexes were characterized by (1)H, (19)F
      and (13)C NMR spectroscopy, HRMS (ESI) as well as single crystal X-ray analysis.
      Bioactivity investigations including bio-assay, time- and dose-dependent, cell
      cycle progression study, caspase 3 and 9 apoptosis marker assay and DNA
      interaction using pBR322 plasmid DNA by gel electrophoresis were performed. The
      results indicated that the complexes showed promising in vitro cytotoxicity in
      MCF-7 and A549 cancer cell lines. Moreover these complexes enhanced the
      expression of p53 tumor suppressor gene family members such as p63 and p73.

PMID- 25939862
TI  - Complete Oculomotor Nerve Palsy Caused by Direct Compression of the Posterior
      Cerebral Artery.
AB  - Oculomotor nerve palsy frequently occurs because of external compression by an
      internal carotid-posterior communicating artery aneurysm and diabetes mellitus.
      In addition, pontine infarction, cavernous sinus tumors, demyelinating disease,
      and autoimmune disorder are well-known causes of oculomotor nerve palsy. However,
      cases of complete oculomotor nerve palsy by neurovascular conflicts presented
      with a sudden onset of clinical symptoms are extremely rare. We experienced a
      rare case of complete oculomotor nerve palsy because of direct vascular
      compression of the oculomotor nerve by the posterior cerebral artery. 

PMID- 25939863
TI  - Prognosis of Early-Stage Continuous Electrocardiogram Abnormalities on Patients
      with Acute Ischemic Stroke.
AB  - BACKGROUND: To explore the effects of onset time of electrocardiogram (ECG)
      abnormalities at an early stage of acute ischemic stroke on patient prognosis.
      Cardiac dysfunction after stroke is a challenge for clinicians. This is a
      retrospective study of patients in the neurology departments of 23 hospitals in
      Shanghai and Wuhan, China. METHODS: The medical records of 351 patients were
      compared. Chi-square, Kruskal-Wallis, Mann-Whitney U tests, and stratification
      compared subgroups. Logistic regressions analyzed factors associated with
      modified Rankin Scale (mRS) score. RESULTS: ECG abnormalities occurred in 70.1%
      of patients at an early stage (most were within 48 hours of disease onset) at
      least once, whereas 45.9% of the patients had ECG abnormalities within 48 hours
      of onset and at 7 days after onset. The incidence of poor prognosis (mRS >1) was
      significantly higher in the patients with ECG abnormalities for both time points
      than that in those with normal ECGs (56.3% versus 32%, odds ratio = 2.166). Most
      patients demonstrated 1 to 2 ECG abnormalities, and very few patients had 3 or
      more. Increasing number of ECG abnormalities was mirrored by poorer prognosis.
      ECG abnormalities occurred within 48 hours and at the seventh day after onset of
      acute ischemic stroke; the abnormalities that appeared within 48 hours and were
      still found on the seventh day after onset of the disease were independent
      predictors of poor patient prognosis. CONCLUSIONS: The incidence of abnormal ECGs
      was high in the patients with acute ischemic stroke, and the abnormal ECGs could
      appear at any stage of the disease.

PMID- 25939864
TI  - Rubrene crystal field-effect mobility modulation via conducting channel
      wrinkling.
AB  - With the impending surge of flexible organic electronic technologies, it has
      become essential to understand how mechanical deformation affects the electrical
      performance of organic thin-film devices. Organic single crystals are ideal for
      the systematic study of strain effects on electrical properties without being
      concerned about grain boundaries and other defects. Here we investigate how the
      deformation affects the field-effect mobility of single crystals of the benchmark
      semiconductor rubrene. The wrinkling instability is used to apply local strains
      of different magnitudes along the conducting channel in field-effect transistors.
      We discover that the mobility changes as dictated by the net strain at the
      dielectric/semiconductor interface. We propose a model based on the plate bending
      theory to quantify the net strain in wrinkled transistors and predict the change
      in mobility. These contributions represent a significant step forward in
      structure-function relationships in organic semiconductors, critical for the
      development of the next generation of flexible electronic devices. 

PMID- 25939865
TI  - On the limits of complexity in living forms.
AB  - In a recent book chapter, Morris, S.C., 2013. Life: the final frontier for
      complexity? In: Lineweaver, C.H., Davies, P.C.W., Ruse, M. (Eds.), Complexity and
      the Arrow of Time. pp. 135-161. argues that there are limits to the complexity of
      life forms and that with the exception of human beings these limits have already
      been reached. We recommend seeing human use of technology as a natural,
      evolutionary process. We then proceed to claim that biological engineering other
      species to increase their complexity can be an efficient way to delay the heat
      death locally. Whenever, wherever in the universe living things become
      intelligent enough to perform these kinds of operations, they will be able to
      increase complexity around them as long as a gradient of energy is available.
      This conclusion has deep impact on both science and philosophy. 

PMID- 25939866
TI  - A theoretical framework for whole-plant carbon assimilation efficiency based on
      metabolic scaling theory: a test case using Picea seedlings.
AB  - Simultaneous and accurate measurements of whole-plant instantaneous carbon-use
      efficiency (ICUE) and annual total carbon-use efficiency (TCUE) are difficult to
      make, especially for trees. One usually estimates ICUE based on the net
      photosynthetic rate or the assumed proportional relationship between growth
      efficiency and ICUE. However, thus far, protocols for easily estimating annual
      TCUE remain problematic. Here, we present a theoretical framework (based on the
      metabolic scaling theory) to predict whole-plant annual TCUE by directly
      measuring instantaneous net photosynthetic and respiratory rates. This framework
      makes four predictions, which were evaluated empirically using seedlings of nine
      Picea taxa: (i) the flux rates of CO(2) and energy will scale isometrically as a
      function of plant size, (ii) whole-plant net and gross photosynthetic rates and
      the net primary productivity will scale isometrically with respect to total leaf
      mass, (iii) these scaling relationships will be independent of ambient
      temperature and humidity fluctuations (as measured within an experimental
      chamber) regardless of the instantaneous net photosynthetic rate or dark
      respiratory rate, or overall growth rate and (iv) TCUE will scale isometrically
      with respect to instantaneous efficiency of carbon use (i.e., the latter can be
      used to predict the former) across diverse species. These predictions were
      experimentally verified. We also found that the ranking of the nine taxa based on
      net photosynthetic rates differed from ranking based on either ICUE or TCUE. In
      addition, the absolute values of ICUE and TCUE significantly differed among the
      nine taxa, with both ICUE and temperature-corrected ICUE being highest for Picea
      abies and lowest for Picea schrenkiana. Nevertheless, the data are consistent
      with the predictions of our general theoretical framework, which can be used to
      access annual carbon-use efficiency of different species at the level of an
      individual plant based on simple, direct measurements. Moreover, we believe that
      our approach provides a way to cope with the complexities of different
      ecosystems, provided that sufficient measurements are taken to calibrate our
      approach to that of the system being studied.

PMID- 25939867
TI  - Climatic origins predict variation in photoprotective leaf pigments in response
      to drought and low temperatures in live oaks (Quercus series Virentes).
AB  - Climate is a major selective force in nature. Exploring patterns of inter- and
      intraspecific genetic variation in functional traits may explain how species have
      evolved and may continue evolving under future climate change. Photoprotective
      pigments play an important role in short-term responses to climate stress in
      plants but knowledge of their long-term role in adaptive processes is lacking. In
      this study, our goal was to determine how photoprotective mechanisms,
      morphological traits and their plasticity have evolved in live oaks (Quercus
      series Virentes) in response to different climatic conditions. For this purpose,
      seedlings originating from 11 populations from four live oak species (Quercus
      virginiana, Q. geminata, Q. fusiformis and Q. oleoides) were grown under
      contrasting common environmental conditions of temperature (tropical vs
      temperate) and water availability (droughted vs well-watered). Xanthophyll cycle
      pigments, anthocyanin accumulation, chlorophyll fluorescence parameters and leaf
      anatomical traits were measured. Seedlings originating from more mesic source
      populations of Q. oleoides and Q. fusiformis increased the xanthophyll de
      epoxidation state under water-limiting conditions and showed higher phenotypic
      plasticity for this trait, suggesting adaptation to local climate. Likewise,
      seedlings originating from warmer climates had higher anthocyanin concentration
      in leaves under cold winter conditions but not higher de-epoxidation state.
      Overall, our findings suggest that (i) climate has been a key factor in shaping
      species and population differences in stress tolerance for live oaks, (ii)
      anthocyanins are used under cold stress in species with limited freezing
      tolerance and (iii) xanthophyll cycle pigments are used when photoprotection
      under drought conditions is needed. 

PMID- 25939868
TI  - Removable cast chrome cobalt retainers for extended or indefinite period clinical
      use.
AB  - Patients are frequently being asked to wear orthodontic retainers for as long as
      they want their teeth to remain in the post-treatment position. Fixed retainers,
      which are placed on the lingual surface of anterior teeth only, have the
      advantage of minimal compliance issues but are not without their problems related
      to wire fracture, adhesive failure and potential gingival or periodontal disease.
      Plastic retainers, although associated with relatively good aesthetics and
      compliance, have limitations related to their physical and mechanical properties.
      This paper describes a chrome cobalt metal retainer that could be used as a long
      term retainer with few drawbacks. The properties of chrome cobalt are described
      and the clinical procedure is outlined. 

PMID- 25939869
TI  - The current status of education and career paths of students after completion of
      medical physicist programs in Japan: a survey by the Japanese Board for Medical
      Physicist Qualification.
AB  - To standardize educational programs and clinical training for medical physics
      students, the Japanese Board for Medical Physicist Qualification (JBMP) began to
      accredit master's, doctorate, and residency programs for medical physicists in
      2012. At present, 16 universities accredited by the JBMP offer 22 courses. In
      this study, we aimed to survey the current status of educational programs and
      career paths of students after completion of the medical physicist program in
      Japan. A questionnaire was sent in August 2014 to 32 universities offering
      medical physicist programs. The questionnaire was created and organized by the
      educational course certification committee of the JBMP and comprised two
      sections: the first collected information about the university attended, and the
      second collected information about characteristics and career paths of students
      after completion of medical physicist programs from 2008 to 2014. Thirty
      universities (16 accredited and 14 non-accredited) completed the survey (response
      rate 94 %). A total of 209, 40, and 3 students graduated from the master's,
      doctorate, and residency programs, respectively. Undergraduates entered the
      medical physicist program constantly, indicating an interest in medical physics
      among undergraduates. A large percentage of the students held a bachelor's degree
      in radiological technology (master's program 94 %; doctorate program 70 %);
      graduates obtained a national radiological technologist license. Regarding career
      paths, although the number of the graduates who work as medical physicist remains
      low, 7 % with a master's degree and 50 % with a doctorate degree worked as
      medical physicists. Our results could be helpful for improving the medical
      physicist program in Japan. 

PMID- 25939871
TI  - Influence of SLCO1B1 polymorphism on maintenance therapy for childhood leukemia.
AB  - BACKGROUND: Management of the adverse effects of chemotherapy is essential to
      improve outcome of children with leukemia. Some genetic polymorphisms can predict
      treatment-related toxicity, and be used individually in dose modification of 6
      mercaptopurine (6-MP) and methotrexate (MTX) in maintenance therapy for childhood
      acute lymphoblastic leukemia (ALL). We investigated associations between clinical
      course and candidate gene polymorphisms less evaluated in Japanese patients.
      METHODS: Fifty-three children who received maintenance chemotherapy were enrolled
      in this study. The scheduled dose of oral 6-MP was 40 mg/m(2) daily and that of
      oral MTX was 25 mg/m(2) weekly. The doses were adjusted according to white blood
      cell count (target range, 2.5-3.5 * 10(9) /L) and aspartate aminotransferase and
      alanine aminotransferase level (< 750 IU/L). Eight polymorphisms in six candidate
      genes, TPMT, ITPA, MRP4, MTHFR, RFC1, and SLCO1B1, were genotyped using the
      Taqman PCR method. Clinical course was reviewed retrospectively from medical
      records. RESULTS: The average dose of 6-MP was lower in the patients with at
      least one variant allele at SLCO1B1 c.521 T > C than in the patients with wild
      homozygous genotype. The other analyzed polymorphisms were not associated with
      toxicity, 6-MP, or MTX dose. CONCLUSIONS: Polymorphism of SLCO1B1 c.521 T > C
      could be a strong predictor of 6-MP dose reduction in maintenance chemotherapy in
      childhood ALL.

PMID- 25939872
TI  - Epitheliocystis in lake trout Salvelinus namaycush (Walbaum) is associated with a
      beta-proteobacteria.
AB  - Lake trout Salvelinus namaycush (Walbaum) raised for stocking experienced yearly
      (2011-13) winter epizootics of epitheliocystis. Affected fish were dispersed on
      the bottom of the tank, had decreased feed and fright response, and mortality
      often reached 40%. Peak mortality occurred within 3 weeks of the appearance of
      clinical signs, and outbreaks typically lasted 6 weeks. Affected fish had no
      gross lesions but histologically had branchial epithelial necrosis and lamellar
      hyperplasia, with small to large numbers of scattered epithelial cells containing
      10- to 20-MUm inclusions. A longitudinal study was undertaken of one annual
      outbreak, and lamellar hyperplasia was most closely associated with mortality.
      The number of inclusions was statistically greater (P < 0.05) before and during
      peak mortality, but inclusions were present in low numbers before clinical signs
      occurred. Results of histochemical staining, immunohistochemistry and
      transmission electron microscopy supported the presence of a beta-proteobacteria
      rather than a Chlamydiales bacterium within inclusions. PCR primers to identify
      Chlamydiales did not give consistent results. However, the use of universal 16S
      rDNA bacterial primers in conjunction with laser capture microdissection of
      inclusions demonstrated that a beta-proteobacteria was consistently associated
      with affected gills and is more likely the cause of the disease in lake trout. 

PMID- 25939870
TI  - ZFP36 stabilizes RIP1 via degradation of XIAP and cIAP2 thereby promoting
      ripoptosome assembly.
AB  - BACKGROUND: ZFP36 is an mRNA binding protein that exerts anti-tumor activity in
      glioblastoma by triggering cell death, associated to an increase in the stability
      of the kinase RIP1. METHODS: We used cell death assays, size exclusion
      chromatography, Co-Immunoprecipitation, shRNA lentivectors and glioma neural stem
      cells to determine the effects of ZFP36 on the assembly of a death complex
      containing RIP1 and on the induction of necroptosis. RESULTS: Here we demonstrate
      that ZFP36 promotes the assembly of the death complex called Ripoptosome and
      induces RIP1-dependent death. This involves the depletion of the ubiquitine
      ligases cIAP2 and XIAP and leads to the association of RIP1 to caspase-8 and
      FADD. Moreover, we show that ZFP36 controls RIP1 levels in glioma neural stem
      cell lines. CONCLUSIONS: We provide a molecular mechanism for the tumor
      suppressor role of ZFP36, and the first evidence for Ripoptosome assembly
      following ZFP36 expression. These findings suggest that ZFP36 plays an important
      role in RIP1-dependent cell death in conditions where IAPs are depleted.

PMID- 25939873
TI  - Limiting CT radiation dose in children with craniosynostosis: phantom study using
      model-based iterative reconstruction.
AB  - BACKGROUND: Medical professionals need to exercise particular caution when
      developing CT scanning protocols for children who require multiple CT studies,
      such as those with craniosynostosis. OBJECTIVE: To evaluate the utility of ultra
      low-dose CT protocols with model-based iterative reconstruction techniques for
      craniosynostosis imaging. MATERIALS AND METHODS: We scanned two pediatric
      anthropomorphic phantoms with a 64-slice CT scanner using different low-dose
      protocols for craniosynostosis. We measured organ doses in the head region with
      metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters. Numerical
      simulations served to estimate organ and effective doses. We objectively and
      subjectively evaluated the quality of images produced by adaptive statistical
      iterative reconstruction (ASiR) 30%, ASiR 50% and Veo (all by GE Healthcare,
      Waukesha, WI). Image noise and contrast were determined for different tissues.
      RESULTS: Mean organ dose with the newborn phantom was decreased up to 83%
      compared to the routine protocol when using ultra-low-dose scanning settings.
      Similarly, for the 5-year phantom the greatest radiation dose reduction was 88%.
      The numerical simulations supported the findings with MOSFET measurements. The
      image quality remained adequate with Veo reconstruction, even at the lowest dose
      level. CONCLUSION: Craniosynostosis CT with model-based iterative reconstruction
      could be performed with a 20-MUSv effective dose, corresponding to the radiation
      exposure of plain skull radiography, without compromising required image quality.

PMID- 25939874
TI  - Morphological tuning via structural modulations in AIE luminogens with the
      minimum number of possible variables and their use in live cell imaging.
AB  - With intent to fine tune the morphological and photophysical properties, three
      novel AIE luminogens (BQ1-BQ3) based on quinoline-BODIPY have been synthesized. A
      judicious choice of substituents (-H, -CH3, -OCH3) in these systems led to
      nanoballs in BQ1 and BQ2, while in BQ3 it led to reticulated nanofibers with
      diverse photophysical behaviours.

PMID- 25939875
TI  - Suppressed inflammatory gene expression during human hypertrophic scar compared
      to normotrophic scar formation.
AB  - Hypertrophic scar formation is a result of adverse cutaneous wound healing. The
      pathogenesis of hypertrophic scar formation is still poorly understood. A problem
      next to the lack of suitable animal models is that often normal skin is compared
      to hypertrophic scar (HTscar) and not to normotrophic scar (NTscar) tissue.
      Another drawback is that often only one time period after wounding is studied,
      while scar formation is a dynamic process over a period of several months. In
      this study, we compared the expression of genes involved in inflammation,
      angiogenesis and extracellular matrix (ECM) formation and also macrophage
      infiltration in biopsies obtained before and up to 52 weeks after standard
      surgery in five patients who developed HTscar and six patients who developed
      NTscar. It was found that HTscar formation coincided with a prolonged decreased
      expression of inflammatory genes (TNFalpha, IL-1alpha, IL-1RN, CCL2, CCL3, CXCL2,
      CXCR2, C3 and IL-10) and an extended increased expression of ECM-related genes
      (PLAU, Col3A1, TGFbeta3). This coincided with a delayed but prolonged
      infiltration of macrophages (type 2) in HTscar tissue compared to NTscar tissue.
      These findings were supported by immunohistochemical localization of proteins
      coding for select genes named above. Our study emphasizes that human cutaneous
      wound healing is a dynamic process that is needed to be studied over a period of
      time rather than a single point of time. Taken together, our results suggest
      innate immune stimulatory therapies may be a better option for improving scar
      quality than the currently used anti-inflammatory scar therapies.

PMID- 25939877
TI  - Author's response: 'Transition considerations for extended half-life factor
      products'.

PMID- 25939876
TI  - Evaluation of Local and Systemic Levels of Interleukin-17, Interleukin-23, and
      Myeloperoxidase in Response to Periodontal Therapy in Patients with Generalized
      Aggressive Periodontitis.
AB  - We aimed to investigate serum and gingival crevicular fluid levels of
      myeloperoxidase, interleukin-17, and interleukin-23 before and after nonsurgical
      periodontal therapy in generalized aggressive periodontitis patients and compare
      to those in healthy controls. Interleukin-17, interleukin-23, and myeloperoxidase
      levels were measured by enzyme-linked immunosorbent assay in gingival crevicular
      fluid and serum samples taken from 19 systemically healthy generalized aggressive
      periodontitis patients and 22 healthy controls. In addition, the levels of IL-17,
      IL-23, and myeloperoxidase were reassessed at 3 months after periodontal therapy
      in the generalized aggressive periodontitis (GAP) group. Periodontal clinical
      parameters were also evaluated at baseline and 3 months post-therapy. The
      investigated molecule levels in serum decreased significantly at 3 months as a
      result of the therapy (p = 0.014 for IL-17, p = 0.000 for IL-23, and p = 0.001
      for myeloperoxidase (MPO)). Significant reductions were also observed in gingival
      crevicular fluid (GCF) IL-17, IL-23, and MPO levels at 3 months after therapy (p
      = 0.000 for all molecules). However, the GCF levels of IL-17, IL-23, and MPO in
      GAP patients were still higher than those in the controls at 3 months (p =
      0.001). A significant decrease in the local and systemic levels of IL-17, IL-23,
      and MPO based on the therapy might indicate the role of these mediators for
      tissue destruction in periodontal tissues. 

PMID- 25939878
TI  - Greatly Enhanced Electronic Conduction and Lithium Storage of Faceted TiO2
      Crystals Supported on Metallic Substrates by Tuning Crystallographic Orientation
      of TiO2.
AB  - Electronic conduction along the [001] direction of a faceted anatase TiO2
      particle in contact with two tungsten probes is found to be an order of magnitude
      higher than that along the [010] direction due to a smaller potential barrier of
      the TiO2 (001)-tungsten interface for electron transport than the TiO2 (010)
      tungsten interface. This finding could guide the design of TiO2 -based
      electrodes. 

PMID- 25939879
TI  - A paper-based microbial fuel cell array for rapid and high-throughput screening
      of electricity-producing bacteria.
AB  - There is a large global effort to improve microbial fuel cell (MFC) techniques
      and advance their translational potential toward practical, real-world
      applications. Significant boosts in MFC performance can be achieved with the
      development of new techniques in synthetic biology that can regulate microbial
      metabolic pathways or control their gene expression. For these new directions, a
      high-throughput and rapid screening tool for microbial biopower production is
      needed. In this work, a 48-well, paper-based sensing platform was developed for
      the high-throughput and rapid characterization of the electricity-producing
      capability of microbes. 48 spatially distinct wells of a sensor array were
      prepared by patterning 48 hydrophilic reservoirs on paper with hydrophobic wax
      boundaries. This paper-based platform exploited the ability of paper to quickly
      wick fluid and promoted bacterial attachment to the anode pads, resulting in
      instant current generation upon loading of the bacterial inoculum. We validated
      the utility of our MFC array by studying how strategic genetic modifications
      impacted the electrochemical activity of various Pseudomonas aeruginosa mutant
      strains. Within just 20 minutes, we successfully determined the electricity
      generation capacity of eight isogenic mutants of P. aeruginosa. These efforts
      demonstrate that our MFC array displays highly comparable performance
      characteristics and identifies genes in P. aeruginosa that can trigger a higher
      power density. 

PMID- 25939880
TI  - Ellis-Van Creveld syndrome: dental management considerations and description of a
      new oral finding.
AB  - Ellis-Van Creveld is a rare syndrome with characteristic dental and orofacial
      findings. Dental management of patients with Ellis-Van Creveld syndrome can be
      complicated by the associated skeletal and cardiac abnormalities. Here, we
      present the dental and orofacial findings in a patient with Ellis-Van Creveld
      syndrome, describe a new oral finding, and discuss the dental management
      considerations. 

PMID- 25939881
TI  - In vivo bone formation by human alveolar-bone-derived mesenchymal stem cells
      obtained during implant osteotomy using biphasic calcium phosphate ceramics or
      Bio-Oss as carriers.
AB  - OBJECTIVES: The aim of this study was to evaluate HA coated with different ratios
      of TCP as a carrier for hABMSCs obtained during implant osteotomy in comparison
      to slowly-resorbing biomaterial, Bio-Oss, as a negative control, using in vitro
      and in vivo experiments. MATERIALS AND METHODS: Human ABMSCs (hABMSCs) harvested
      during implant osteotomy were transplanted using HA/TCP or Bio-Oss as carriers in
      a murine ectopic transplantation model (n = 12). Pore size and cell affinity were
      evaluated in vitro. The area of newly formed bone was analyzed histometrically,
      the number of osteocytes was counted, and immunohistochemical staining was
      conducted against several markers of osteogenesis, including alkaline phosphatase
      (ALP), runt-related transcription factor 2 (RUNX-2), osteocalcin (OCN), and
      osteopontin (OPN). Osteoclast formation was evaluated by tartrate-resistant acid
      phosphatase staining. RESULTS: The carrier materials had comparable pore sizes.
      The cell affinity assay resulted in a high proportion of cell adhesion (>90%) in
      all experimental groups. Substantial new bone and osteocyte formation was
      observed on both HA/TCP carriers, whereas it was minimal with Bio-Oss. Positive
      immunostaining for ALP, RUNX-2, OCN, and OPN was observed with HA/TCP, but only
      limited expression of osteogenic markers with Bio-Oss. Conversely, there was a
      minimal osteoclast presence with Bio-Oss, but a significant presence of
      osteoclasts with both HA/TCP carriers. CONCLUSIONS: Both types of scaffolds, BCP
      and Bio-Oss, showed high stem cell-carrying potential, but the in vivo healing
      patterns of their complexes with hABMSC could be affected by the microenvironment
      on the surfaces of the scaffolds.

PMID- 25939882
TI  - Sphingosine 1-phosphate signaling at the blood-brain barrier.
AB  - The characterization of molecular pathways that modulate blood-brain barrier
      (BBB) function and integrity has been fueled by a growing body of literature
      implicating BBB dysfunction in a wide range of neurologic diseases. Sphingosine 1
      phosphate (S1P) is a pleiotropic signaling molecule that has been effectively
      targeted by the immunomodulatory S1P1 functional antagonist fingolimod in the
      treatment of multiple sclerosis (MS). Investigation into the pathways modulated
      by S1P has revealed its important role in regulating BBB integrity via signaling
      through receptor isoforms on astrocytes and endothelial cells (ECs). Current
      evidence supports a significant role for S1P signaling as a key determinant of
      BBB permeability and hence as a potential pathogenic player or therapeutic target
      in diseases characterized by BBB dysfunction. 

PMID- 25939884
TI  - Ultrathin MoS2 Nanosheets Supported on N-doped Carbon Nanoboxes with Enhanced
      Lithium Storage and Electrocatalytic Properties.
AB  - Molybdenum disulfide (MoS2) has received considerable interest for
      electrochemical energy storage and conversion. In this work, we have designed and
      synthesized a unique hybrid hollow structure by growing ultrathin MoS2 nanosheets
      on N-doped carbon shells (denoted as C@MoS2 nanoboxes). The N-doped carbon shells
      can greatly improve the conductivity of the hybrid structure and effectively
      prevent the aggregation of MoS2 nanosheets. The ultrathin MoS2 nanosheets could
      provide more active sites for electrochemical reactions. When evaluated as an
      anode material for lithium-ion batteries, these C@MoS2 nanoboxes show high
      specific capacity of around 1000 mAh g(-1), excellent cycling stability up to 200
      cycles, and superior rate performance. Moreover, they also show enhanced
      electrocatalytic activity for the electrochemical hydrogen evolution.

PMID- 25939883
TI  - Stress and inflammatory gene networks in bovine liver are altered by plane of
      dietary energy during late pregnancy.
AB  - The prepartal dietary energy level is tightly correlated with the degree of
      tissue mobilization that the animal experiences around parturition (giving
      birth). To better understand the link between the dry period dietary energy
      management and the inflammatory status around parturition, 12 multiparous
      Holstein cows were fed for the entire dry period either a high-wheat straw/lower
      energy diet to supply at least 100% of the calculated net energy for lactation
      (NEL) (control, CON) or a higher-energy diet to supply >140% of NEL (overfed,
      OVE). The blood was sampled throughout the transition period for biomarker
      analyses. Liver tissue samples were taken on days -14, 7, 14, and 30 relative to
      parturition for triacylglycerol (TAG) composition and gene expression analysis.
      Fifty genes involved in inflammation, endoplasmic reticulum (ER), and oxidative
      stress, and cell cycle and growth were evaluated. Although blood biomarkers did
      not reveal signs of a greater inflammatory status compared with OVE, CON cows had
      a greater activation of the intrahepatic unfolded protein response prepartum.
      However, postpartum mRNA profiling indicated that the OVE group experienced a
      mild but sustained level of ER stress, with higher oxidative stress and
      impairment of antioxidant mechanisms. After parturition, inflammation-related
      genes were upregulated in OVE cows compared with CON. However, CON cows
      experienced a gradual increase in expression of key inflammatory transcription
      regulators up to 30 days postpartum which agreed with the lower plasma albumin
      and cholesterol, suggesting an inflammatory state. Data underscored that ER
      stress is not necessarily linked with inflammation during the peripartal period.
      Gene expression data also suggest that prepartum overnutrition could have
      negative effects on normal cell cycle activity. Overall, allowing cows to
      overconsume energy prepartum increased the hepatic pro-inflammatory response
      prepartum and up to the point of parturition. Subsequently, cows fed the lower
      energy diet experienced a gradual increase in the inflammatory response. The lack
      of differences between groups in voluntary feed intake and lactation capacity
      suggests that nutritional management prepartum triggers different mechanisms that
      affect ER and oxidative stress along with inflammation. Although no clinical
      disorders were detected, these alterations expose animals to the development of
      immuno-metabolic disorders.

PMID- 25939885
TI  - Comparative pathogenesis of US porcine epidemic diarrhea virus (PEDV) strain
      PC21A in conventional 9-day-old nursing piglets vs. 26-day-old weaned pigs.
AB  - Our study demonstrated potential mechanisms by which porcine epidemic diarrhea
      virus (PEDV) infection induces greater disease severity of nursing vs. weaned
      conventional pigs. Twenty-six-day-old weaned [PEDV-inoculated (n=11); mock (n=9)]
      and 9-day-old nursing pigs [PEDV-inoculated (n=9); mock (n=11)] were inoculated
      orally [8.9 log10 genomic equivalents (GE)/pig] with PC21A strain or mock (MEM).
      Pigs were monitored for clinical signs and PEDV RNA titers in feces and serum.
      For pathology and immunofluorescence staining for Ki67 (marker for crypt
      proliferation) and LGR5 (marker for crypt stem cell), 3-4 pigs were euthanized at
      postinoculation days (PIDs) 1, 3 and 5. Severe watery diarrhea and atrophic
      enteritis with moderate to high PEDV RNA titers in feces (7.5-12.2 log10 GE/ml)
      and low viral RNA titers in serum (5.6-8.6 log10 GE/ml) were observed in all
      inoculated nursing piglets at PIDs 1-5. In contrast, weaned pigs did not show
      evidence of PEDV infection at PID 1. Pigs exhibited high fecal shedding titers at
      PIDs 2-5 and mild to severe atrophic enteritis at PIDs 3-5, indicating a longer
      incubation for PEDV infection. While uninoculated or inoculated 27-31-day-old
      pigs showed large numbers of Ki67- or LGR5-positive cells in the intestinal
      crypts, there was a lack of LGR5-positive cells and low proliferation of crypts
      in jejunum of uninoculated 10-14-day-old piglets, possibly causing a slower
      turnover of enterocytes; however, the number of LGR5-positive cells and
      proliferation of intestinal crypts increased remarkably at 3-5 days after
      inoculation. Biologic mediators that promote crypt stem cell regeneration would
      be targets to improve the intestinal epithelium renewal during PEDV infection. 

PMID- 25939887
TI  - Use of Digital Pens for Rapid Epidemiologic Data Collection During a Foodborne
      Outbreak Investigation.
AB  - OBJECTIVE: Public health investigations require rapid assessment, response, and
      initiation of control measures. In 2012, the New Hampshire Department of Health
      and Human Services used digital pens to rapidly acquire epidemiologic data during
      a gastrointestinal illness outbreak. METHODS: Menus were obtained and a standard
      questionnaire was administered to exposed persons using digital pens.
      Questionnaire data were downloaded into an electronic file for analysis. RESULTS:
      Sixty-nine (74%) of 93 exposed persons completed a questionnaire. Of 6389 data
      entries made on digital paper, 218 (3%) required correction; of these, 201 (92%)
      involved a free-form variable and 17 (8%) involved a check-box variable. Digital
      pens saved an estimated 5 to 6 hours of data-entry time. CONCLUSIONS: This
      outbreak provided an opportunity to assess the value of digital pens for
      decreasing data-entry burden and allowing more timely data analysis in an
      emergent setting. Depending on the size of the outbreak and complexity of the
      survey, there is likely a threshold when use of digital pens would provide a
      clear benefit to outbreak response. As new technology becomes available for use
      in emergency preparedness settings, public health agencies must continuously
      review and update response plans and evaluate investigation tools to ensure
      timely disease control and response activities.

PMID- 25939886
TI  - LRRK2 dephosphorylation increases its ubiquitination.
AB  - Activating mutations in the leucine rich repeat protein kinase 2 (LRRK2) gene are
      the most common cause of inherited Parkinson's disease (PD). LRRK2 is
      phosphorylated on a cluster of phosphosites including Ser(910), Ser(935),
      Ser(955) and Ser(973), which are dephosphorylated in several PD-related LRRK2
      mutants (N1437H, R1441C/G, Y1699C and I2020T) linking the regulation of these
      sites to PD. These serine residues are also dephosphorylated after kinase
      inhibition and lose 14-3-3 binding, which serves as a pharmacodynamic marker for
      inhibited LRRK2. Loss of 14-3-3 binding is well established, but the consequences
      of dephosphorylation are only now being uncovered. In the present study, we found
      that potent and selective inhibition of LRRK2 kinase activity leads to
      dephosphorylation of Ser(935) then ubiquitination and degradation of a
      significant fraction of LRRK2. GNE1023 treatment decreased the phosphorylation
      and stability of LRRK2 in expression systems and endogenous LRRK2 in A549 cells
      and in mouse dosing studies. We next established that LRRK2 is ubiquitinated
      through at least Lys(48) and Lys(63) ubiquitin linkages in response to
      inhibition. To investigate the link between dephosphorylation induced by
      inhibitor treatment and LRRK2 ubiquitination, we studied LRRK2 in conditions
      where it is dephosphorylated such as expression of PD mutants [R1441G, Y1699C and
      I2020T] or by blocking 14-3-3 binding to LRRK2 via difopein expression, and found
      LRRK2 is hyper-ubiquitinated. Calyculin A treatment prevents inhibitor and PD
      mutant induced dephosphorylation and reverts LRRK2 to a lesser ubiquitinated
      species, thus directly implicating phosphatase activity in LRRK2 ubiquitination.
      This dynamic dephosphorylation-ubiquitination cycle could explain detrimental
      loss-of-function phenotypes found in peripheral tissues of LRRK2 kinase inactive
      mutants, LRRK2 KO (knockout) animals and following LRRK2 inhibitor
      administration. 

PMID- 25939888
TI  - Violent suicidal behaviour in bipolar disorder is associated with nitric oxide
      synthase 3 gene polymorphism.
AB  - OBJECTIVE: Given the importance of nitric oxide system in oxidative stress,
      inflammation, neurotransmission and cerebrovascular tone regulation, we
      postulated its potential dysfunction in bipolar disorder (BD) and suicide. By
      simultaneously analysing variants of three isoforms of nitric oxide synthase
      (NOS) genes, we explored interindividual genetic liability to suicidal behaviour
      in BD. METHOD: A total of 536 patients with BD (DSM-IV) and 160 healthy controls
      were genotyped for functionally relevant NOS1, NOS2 and NOS3 polymorphisms.
      History of suicidal behaviour and violent suicide attempt was documented for 511
      patients with BD. Chi-squared test was used to perform genetic association
      analyses and logistic regression to test for gene-gene interactions. RESULTS:
      NOS3 rs1799983 T homozygous state was associated with violent suicide attempts
      (26.4% vs. 10.8%, in patients and controls, P = 0.002, corrected P (Pc) = 0.004,
      OR: 2.96, 95% CI = 1.33-6.34), and this association was restricted to the early
      onset BD subgroup (37.9% vs. 10.8%, in early-onset BD and controls, P = 0.0003,
      Pc = 0.0006 OR: 5.05, 95% CI: 1.95-12.45), while we found no association with BD
      per se and no gene-gene interactions. CONCLUSION: Our results bring further
      evidence for the potential involvement of endothelial NOS gene variants in
      susceptibility to suicidal behaviour. Future exploration of this pathway on
      larger cohort of suicidal behaviour is warranted.

PMID- 25939889
TI  - Pursuing DNA catalysts for protein modification.
AB  - Catalysis is a fundamental chemical concept, and many kinds of catalysts have
      considerable practical value. Developing entirely new catalysts is an exciting
      challenge. Rational design and screening have provided many new small-molecule
      catalysts, and directed evolution has been used to optimize or redefine the
      function of many protein enzymes. However, these approaches have inherent
      limitations that prompt the pursuit of different kinds of catalysts using other
      experimental methods. Nature evolved RNA enzymes, or ribozymes, for key catalytic
      roles that in modern biology are limited to phosphodiester cleavage/ligation and
      amide bond formation. Artificial DNA enzymes, or deoxyribozymes, have great
      promise for a broad range of catalytic activities. They can be identified from
      unbiased (random) sequence populations as long as the appropriate in vitro
      selection strategies can be implemented for their identification. Notably, in
      vitro selection is different in key conceptual and practical ways from rational
      design, screening, and directed evolution. This Account describes the development
      by in vitro selection of DNA catalysts for many different kinds of covalent
      modification reactions of peptide and protein substrates, inspired in part by our
      earlier work with DNA-catalyzed RNA ligation reactions. In one set of studies, we
      have sought DNA-catalyzed peptide backbone cleavage, with the long-term goal of
      artificial DNA-based proteases. We originally anticipated that amide hydrolysis
      should be readily achieved, but in vitro selection instead surprisingly led to
      deoxyribozymes for DNA phosphodiester hydrolysis; this was unexpected because
      uncatalyzed amide bond hydrolysis is 10(5)-fold faster. After developing a
      suitable selection approach that actively avoids DNA hydrolysis, we were able to
      identify deoxyribozymes for hydrolysis of esters and aromatic amides (anilides).
      Aliphatic amide cleavage remains an ongoing focus, including via inclusion of
      chemically modified DNA nucleotides in the catalyst, which we have recently found
      to enable this cleavage reaction. In numerous other efforts, we have investigated
      DNA-catalyzed peptide side chain modification reactions. Key successes include
      nucleopeptide formation (attachment of oligonucleotides to peptide side chains)
      and phosphatase and kinase activities (removal and attachment of phosphoryl
      groups to side chains). Through all of these efforts, we have learned the
      importance of careful selection design, including the frequent need to develop
      specific "capture" reactions that enable the selection process to provide only
      those DNA sequences that have the desired catalytic functions. We have
      established strategies for identifying deoxyribozymes that accept discrete
      peptide and protein substrates, and we have obtained data to inform the key
      choice of random region length at the outset of selection experiments. Finally,
      we have demonstrated the viability of modular deoxyribozymes that include a small
      molecule-binding aptamer domain, although the value of such modularity is found
      to be minimal, with implications for many selection endeavors. Advances such as
      those summarized in this Account reveal that DNA has considerable catalytic
      abilities for biochemically relevant reactions, specifically including covalent
      protein modifications. Moreover, DNA has substantially different, and in many
      ways better, characteristics than do small molecules or proteins for a catalyst
      that is obtained "from scratch" without demanding any existing information on
      catalyst structure or mechanism. Therefore, prospects are very strong for
      continued development and eventual practical applications of deoxyribozymes for
      peptide and protein modification. 

PMID- 25939890
TI  - The fractionated dipole antenna: A new antenna for body imaging at 7 Tesla.
AB  - PURPOSE: Dipole antennas in ultrahigh field MRI have demonstrated advantages over
      more conventional designs. In this study, the fractionated dipole antenna is
      presented: a dipole where the legs are split into segments that are
      interconnected by capacitors or inductors. METHODS: A parameter study has been
      performed on dipole antenna length using numerical simulations. A subsequent
      simulation study investigates the optimal intersegment capacitor/inductor value.
      The resulting optimal design has been constructed and compared to a previous
      design, the single-side adapted dipole (SSAD) by simulations and measurements. An
      array of eight elements has been constructed for prostate imaging on four
      subjects (body mass index 20-27.5) using 8 * 2 kW amplifiers. RESULTS: For
      prostate imaging at 7T, lowest peak local specific-absorption rate (SAR) levels
      are achieved if the antenna is 30 cm or longer. A fractionated dipole antenna
      design with inductors between segments has been chosen to achieve even lower SAR
      levels and more homogeneous receive sensitivities. CONCLUSION: With the new
      design, good quality prostate images are acquired. SAR levels are reduced by 41%
      to 63% in comparison to the SSAD. Coupling levels are moderate (average nearest
      neighbor: -14.6 dB) for each subject and prostate B1+ levels range from 12 to 18
      MUT.

PMID- 25939891
TI  - [Local combination therapy of inflammatory dermatomycosis: A review of
      recommendations in national and international guidelines].
AB  - BACKGROUND: Dermatomycosis, caused by fungi or dermatophytes is often accompanied
      by considerable inflammatory changes and is, therefore, of great clinical
      significance. Hence, it is reasonable to eliminate both the pathogen and all
      signs of inflammation by applying a drug combination of antimycotic and
      corticosteroid. OBJECTIVES: How do national and international guidelines support
      this kind of therapy? Does consensus prevail, or are there a variety of
      recommendations? MATERIALS AND METHODS: The present article uses the
      internationally recognized scientific search method to evaluate pharmaceuticals
      and discusses the results of the international recommendations. RESULTS: The use
      of a corticosteroid/antimycotic combination therapy for the treatment of various
      types of inflammatory dermatomycosis is explicitly recommended by national and
      international guidelines. Although two significant German guidelines for
      treatment of dermatomycoses do not include usage of combination preparations, in
      view of their current relevance, however, their adaptation to international
      recommendations appears to make sense.

PMID- 25939893
TI  - Impact of solar ultraviolet B radiation (290-320 nm) on vitamin D synthesis in
      children with type IV and V skin.

PMID- 25939892
TI  - Congenital cardiac anomalies and white matter injury.
AB  - Cardiac abnormalities are the most common birth defects. Derangement of
      circulatory flow affects many vital organs; without proper supply of oxygenated
      blood, the brain is particularly vulnerable. Although surgical interventions have
      greatly reduced mortality rates, patients often suffer an array of neurological
      deficits throughout life. Neuroimaging provides a macroscopic assessment of brain
      injury and has shown that white matter (WM) is at risk. Oligodendrocytes and
      myelinated axons have been identified as major targets of WM injury, but still
      little is known about how congenital heart anomalies affect the brain at the
      cellular level. Further integration of animal model studies and clinical research
      will define novel therapeutic targets and new standards of care to prevent
      developmental delay associated with cardiac abnormalities. 

PMID- 25939894
TI  - Cilengitide combined with cetuximab and platinum-based chemotherapy as first-line
      treatment in advanced non-small-cell lung cancer (NSCLC) patients: results of an
      open-label, randomized, controlled phase II study (CERTO).
AB  - BACKGROUND: This multicentre, open-label, randomized, controlled phase II study
      evaluated cilengitide in combination with cetuximab and platinum-based
      chemotherapy, compared with cetuximab and chemotherapy alone, as first-line
      treatment of patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS
      AND METHODS: Patients were randomized 1:1:1 to receive cetuximab plus platinum
      based chemotherapy alone (control), or combined with cilengitide 2000 mg 1*/week
      i.v. (CIL-once) or 2*/week i.v. (CIL-twice). A protocol amendment limited
      enrolment to patients with epidermal growth factor receptor (EGFR) histoscore
      >=200 and closed the CIL-twice arm for practical feasibility issues. Primary end
      point was progression-free survival (PFS; independent read); secondary end points
      included overall survival (OS), safety, and biomarker analyses. A comparison
      between the CIL-once and control arms is reported, both for the total cohorts, as
      well as for patients with EGFR histoscore >=200. RESULTS: There were 85 patients
      in the CIL-once group and 84 in the control group. The PFS (independent read) was
      6.2 versus 5.0 months for CIL-once versus control [hazard ratio (HR) 0.72; P =
      0.085]; for patients with EGFR histoscore >=200, PFS was 6.8 versus 5.6 months,
      respectively (HR 0.57; P = 0.0446). Median OS was 13.6 for CIL-once versus 9.7
      months for control (HR 0.81; P = 0.265). In patients with EGFR >=200, OS was 13.2
      versus 11.8 months, respectively (HR 0.95; P = 0.855). No major differences in
      adverse events between CIL-once and control were reported; nausea (59% versus
      56%, respectively) and neutropenia (54% versus 46%, respectively) were the most
      frequent. There was no increased incidence of thromboembolic events or
      haemorrhage in cilengitide-treated patients. alphavbeta3 and alphavbeta5
      expression was neither a predictive nor a prognostic indicator. CONCLUSIONS: The
      addition of cilengitide to cetuximab/chemotherapy indicated potential clinical
      activity, with a trend for PFS difference in the independent-read analysis.
      However, the observed inconsistencies across end points suggest additional
      investigations are required to substantiate a potential role of other integrin
      inhibitors in NSCLC treatment. CLINICAL TRIAL REGISTRATION ID NUMBER:
      NCT00842712.

PMID- 25939895
TI  - Reply to the letter to the editor 'duration of endocrine therapy and its impact
      on the results of adjuvant trials in premenopausal breast cancer patients' by
      Fouad et al.

PMID- 25939898
TI  - Mediastinal granulomatous lymphadenitis in a population at risk for HIV and
      tuberculosis.
AB  - BACKGROUND: Granulomatous inflammation on transbronchial needle aspirates from
      mediastinal lymph nodes is an infrequent yet important finding. We determined
      associations between cytomorphological features and underlying aetiology in an
      area of high prevalence of HIV-infection and tuberculosis. METHODS: We identified
      cases with granulomatous inflammation on mediastinal aspirates from January 2003
      to July 2010. Cytomorphological features were evaluated and graded according to a
      simple and reproducible system including the presence, quality (discrete or
      vague), and number (<=5 or more) of granulomas as well as the presence of
      necrosis, lymphocytes, multinucleated giant cells, and neutrophils. RESULTS: In
      81 patients (36 male, 9 HIV-positive) the final diagnosis was tuberculosis in 37
      (46%), sarcoidosis in 40 (49%), fibrosing mediastinitis in 1 (1%), and unknown in
      3 (4%). The presence of necrosis (P < 0.001) and neutrophils (P = 0.05) was
      associated with tuberculosis and numerous discrete granulomas were associated
      with sarcoidosis (P = 0.03). All HIV-positive patients were diagnosed with
      tuberculosis. CONCLUSION: Granulomatous disease identified on TBNA from
      mediastinal lymph nodes is mostly associated with sarcoidosis and tuberculosis.
      Ancillary investigations for sarcoidosis are appropriate if numerous discrete
      granulomas are found. Tuberculosis must be excluded if necrosis and neutrophils
      are present and in HIV-positive individuals, particularly in high-burden areas of
      tuberculosis.

PMID- 25939897
TI  - Treatment of patients with diabetic peripheral neuropathic pain in China: a
      double-blind randomised trial of duloxetine vs. placebo.
AB  - BACKGROUND: Duloxetine has been approved in the United States, European Union and
      some Asian countries for the treatment of diabetic peripheral neuropathic pain
      (DPNP). We assessed the efficacy and safety of duloxetine (60 mg once daily)
      compared with placebo in Chinese patients suffering from DPNP. METHODS: This was
      a phase 3, multicenter, randomised, double-blind, parallel, placebo-controlled,
      12-week trial of the treatment of DPNP with duloxetine. Subjects were male and
      female outpatients >= 18 years of age with DPNP, as assessed by the Michigan
      Neuropathy Screening Instrument, and had a rating of >= 4 on the Brief Pain
      Inventory-Modified Short Form-Severity weekly average pain item. The primary
      efficacy measure was the reduction in pain severity from baseline to 12 weeks, as
      measured by the weekly mean of 24-h average pain ratings recorded in the
      patient's diary. Mean changes from baseline in efficacy measures were analysed by
      a restricted maximum likelihood-based, mixed-effects model repeated measures
      approach and by analysis of covariance. RESULTS: Of the 405 patients randomised,
      203 patients were assigned to duloxetine 60 mg once daily and 202 patients were
      assigned to placebo. Duloxetine-treated patients showed significantly greater
      pain relief on 24-h average pain ratings compared with placebo-treated patients
      each week of the 12-week study period [week 12: least squares (LS) mean change
      duloxetine: -2.40, placebo: -1.97; LS mean change difference (95% confidence
      interval) = -0.43 (-0.82, -0.04), p = 0.030]. Compared with placebo, patients
      treated with duloxetine experienced higher rates of nausea (p = 0.010),
      somnolence (p < 0.001) and asthenia (p = 0.002). CONCLUSIONS: Duloxetine-treated
      patients showed significantly greater pain relief compared with placebo-treated
      patients over the 12-week study period. Duloxetine was shown in Chinese patients
      to have a safety profile similar to that found in previous duloxetine trials.

PMID- 25939900
TI  - Should universities play a greater role in the delivery of emergency medicine
      specialty education and training? No.

PMID- 25939896
TI  - Tailoring therapies--improving the management of early breast cancer: St Gallen
      International Expert Consensus on the Primary Therapy of Early Breast Cancer
      2015.
AB  - The 14th St Gallen International Breast Cancer Conference (2015) reviewed
      substantial new evidence on locoregional and systemic therapies for early breast
      cancer. Further experience has supported the adequacy of tumor margins defined as
      'no ink on invasive tumor or DCIS' and the safety of omitting axillary dissection
      in specific cohorts. Radiotherapy trials support irradiation of regional nodes in
      node-positive disease. Considering subdivisions within luminal disease, the Panel
      was more concerned with indications for the use of specific therapies, rather
      than surrogate identification of intrinsic subtypes as measured by multiparameter
      molecular tests. For the treatment of HER2-positive disease in patients with node
      negative cancers up to 1 cm, the Panel endorsed a simplified regimen comprising
      paclitaxel and trastuzumab without anthracycline as adjuvant therapy. For
      premenopausal patients with endocrine responsive disease, the Panel endorsed the
      role of ovarian function suppression with either tamoxifen or exemestane for
      patients at higher risk. The Panel noted the value of an LHRH agonist given
      during chemotherapy for premenopausal women with ER-negative disease in
      protecting against premature ovarian failure and preserving fertility. The Panel
      noted increasing evidence for the prognostic value of commonly used
      multiparameter molecular markers, some of which also carried prognostic
      information for late relapse. The Panel noted that the results of such tests,
      where available, were frequently used to assist decisions about the inclusion of
      cytotoxic chemotherapy in the treatment of patients with luminal disease, but
      noted that threshold values had not been established for this purpose for any of
      these tests. Multiparameter molecular assays are expensive and therefore
      unavailable in much of the world. The majority of new breast cancer cases and
      breast cancer deaths now occur in less developed regions of the world. In these
      areas, less expensive pathology tests may provide valuable information. The Panel
      recommendations on treatment are not intended to apply to all patients, but
      rather to establish norms appropriate for the majority. Again, economic
      considerations may require that less expensive and only marginally less effective
      therapies may be necessary in less resourced areas. Panel recommendations do not
      imply unanimous agreement among Panel members. Indeed, very few of the 200
      questions received 100% agreement from the Panel. In the text below, wording is
      intended to convey the strength of Panel support for each recommendation, while
      details of Panel voting on each question are available in supplementary Appendix
      S2, available at Annals of Oncology online. 

PMID- 25939899
TI  - Oxidant and enzymatic antioxidant status (gene expression and activity) in the
      brain of chickens with cold-induced pulmonary hypertension.
AB  - To evaluate oxidant and antioxidant status of the brain (hindbrain, midbrain, and
      forebrain) in chickens with cold-induced pulmonary hypertension, the measurements
      of lipid peroxidation, protein oxidation, antioxidant capacity, enzymatic
      activity, and gene expression (for catalase, glutathione peroxidase, and
      superoxide dismutases) were done. There were high lipid peroxidation/protein
      oxidation and low antioxidant capacity in the hindbrain of cold-induced pulmonary
      hypertensive chickens compared to control (P < 0.05). In the hypertensive
      chickens, superoxide dismutase activity was decreased (forebrain, midbrain, and
      hindbrain), while catalase activity was increased (forebrain and midbrain) (P <
      0.05). Glutathione peroxidase activity did not change. Relative gene expression
      of catalase and superoxide dismutases (1 and 2) was downregulated, while
      glutathione peroxidase was upregulated in the brain of the cold-induced pulmonary
      hypertensive chickens. Probably, these situations in the oxidant and antioxidant
      status of the brain especially hindbrain may change its function at
      cardiovascular center and sympathetic nervous system to exacerbate pulmonary
      hypertension.

PMID- 25939901
TI  - Severe mucositis after acute substance ingestion.

PMID- 25939902
TI  - Separation of anthraquinone compounds from the seed of Cassia obtusifolia L.
      using recycling counter-current chromatography.
AB  - Recycling counter-current chromatography (CCC) together with step-gradient CCC
      and medium-pressure liquid chromatography (MPLC) was employed to separate nine
      anthraquinone compounds from Cassia obtusifolia L. in this study. The results
      showed that recycling CCC is a powerful tool for compounds that are difficult to
      separate with common elution mode. CCC was the better option for crude material
      while MPLC had advantage for the final tuning. The combination of recycling CCC
      and MPLC could simplify the method exploring process in the separation process.
      The structures of these compounds were identified according to their mass
      spectra, by (1)H-NMR and compared with standard compounds. 

PMID- 25939903
TI  - Erratum to: Immunotherapeutic Approach to Cancer with Cutaneous DNA Vaccination.

PMID- 25939904
TI  - Thermoelectric Properties of Nanowires with a Graphitic Shell.
AB  - A thermoelectric device that can generate electricity from waste heat can play an
      important role in a global energy solution. However, the strongly correlated
      thermoelectric properties have remained a major hurdle for the highly efficient
      conversion of thermoelectric energy. Herein, the electrical and thermal
      properties of Si and SiO2 nanowires with few-layer graphitic shells are
      demonstrated; these structures exhibit enhanced electrical properties but no
      increase in thermal conductivity. The main path of the phonons through the
      structures is the core nanowire, which has a large cross-sectional area relative
      to that of the graphitic shell layer. However, the electrical conductivities of
      the nanowires with shell structures are high because of the good electrical
      conductivity of the graphitic shell, despite its small cross-sectional area. 

PMID- 25939905
TI  - Predictors of acute kidney injury after coronary artery surgery in Jordanians.
AB  - BACKGROUND: Acute kidney injury after coronary artery bypass surgery is
      associated with increased morbidity and mortality. We investigated the predictors
      of acute kidney injury in a major hospital in Jordan. METHODS: A retrospective
      analysis was conducted of clinical, operative, and outcome data of 867 patients
      (mean age 59 +/- 9.8 years) who underwent isolated coronary bypass surgery with
      cardiopulmonary bypass. Acute kidney injury postoperatively, defined as >=100%
      increase in serum creatinine level, was the outcome variable. Retrospective
      clinical, laboratory, and demographic data, and medication use, were obtained
      from electronic medical records. RESULTS: Univariate analysis revealed that
      chronic obstructive pulmonary disease, recent myocardial infarction, emergency
      surgery, preoperative intraaortic balloon pump use, left atrial size >4 cm, grade
      1 mitral regurgitation, pneumonia, intensive care unit stay, prolonged
      vasopressor support, and stroke or transient ischemic attack were significantly
      associated with postoperative renal failure. On multivariate logistic regression,
      emergency surgery (adjusted odds ratio = 2.17, p = 0.017), grade 1 mitral
      regurgitation (adjusted odds ratio = 2.05, p = 0.020), prolonged support
      (adjusted odds ratio = 3.16, p = 0.000), and stroke (adjusted odds ratio = 20.1,
      p = 0.004) were independent predictors of kidney injury following coronary bypass
      surgery. CONCLUSION: Emergency coronary surgery, mitral regurgitation, prolonged
      inotropic support, and stroke or transient ischemic attack are independent
      predictors of acute kidney injury following coronary bypass surgery. Further
      studies involving patients with isolated coronary bypass surgery as well as valve
      and combined surgeries may be necessary to complete our understanding of this
      subject.

PMID- 25939906
TI  - Dexmedetomidine in combination with midazolam after pediatric cardiac surgery.
AB  - OBJECTIVE: Although midazolam is one of the most commonly used sedatives for
      infants in the intensive care unit, it has well-known disadvantages including a
      dose-dependent potential to induce tolerance, withdrawal, and hemodynamic
      depression. The aim of this study was to evaluate the clinical effects of
      dexmedetomidine combined with midazolam in postoperative intensive care following
      pediatric cardiac surgery. METHODS: Forty consecutive infants who underwent
      cardiac surgery for isolated ventricular septal defects from January 2011 to July
      2013 were enrolled in this retrospective study. They were divided into two groups
      according to postoperative sedation regimen: dexmedetomidine sedation with
      midazolam (n = 20), or midazolam sedation without dexmedetomidine (control group,
      n = 20). Perioperative variables were compared between the two groups. RESULTS:
      There were no significant differences in patient characteristics between the two
      groups. During the first 24 h after intensive care unit admission, heart rate and
      serum lactate levels were significantly lower in the dexmedetomidine group
      compared to the control group (p = 0.0292 and p = 0.0027, respectively). The
      maximal midazolam dose was also significantly lower in the dexmedetomidine group
      (0.12 +/- 0.09 vs. 0.20 +/- 0.08 mg kg(-1) h(-1), p = 0.0059). There were no
      adverse effects of dexmedetomidine such as bradycardia, hypotension, agitation,
      or seizures. Three (15%) patients in the control group and none in the
      dexmedetomidine group experienced sudden cardiopulmonary decompensation.
      CONCLUSIONS: Dexmedetomidine can provide favorable sedative properties with a
      reduced requirement for concomitant midazolam and stable hemodynamics with
      tachycardia prevention, for postoperative intensive care following pediatric
      cardiac surgery.

PMID- 25939907
TI  - Shuffle the puzzle: Spinal motor-evoked potentials vs. 50-Hz artifact.

PMID- 25939908
TI  - Carbon dioxide insufflation and neurocognitive outcome of open heart surgery.
AB  - AIM: Neurocognitive dysfunction continues to be the bane of open heart surgery
      despite vast improvements in surgical, anesthetic, and postoperative management.
      This observational cohort study was carried out to evaluate the efficacy of
      intraoperative CO2 insufflation by the field flooding technique in reducing
      postoperative neurocognitive dysfunction. METHODS: Three hundred randomly
      selected patients undergoing open heart surgery were observed: 150 (group A) were
      exposed to CO2 insufflation, and the other 150 (group B) were not exposed to CO2.
      Anesthetic, cardiopulmonary bypass, and myocardial protection techniques were
      standardized and similar in both groups. Neurocognitive function tests were
      performed preoperatively, 1 week postoperatively, and after 1 month. RESULTS: The
      analysis revealed that neurocognitive dysfunction occurred in 8 of 150 patients
      in group A (incidence p1 = 0.053) and 27 of 150 in group B (incidence p2 = 0.18).
      The relative risk of neurocognitive dysfunction was 0.30 (p = 0.001, 95%
      confidence interval 0.14-0.63), implying that CO2 insufflation is protective
      against neurocognitive dysfunction. The risk difference was 0.13 (p2-p1); this
      implies that 13% of patients can be prevented from developing neurocognitive
      dysfunction if exposed to CO2. CONCLUSION: This study confirms the known
      advantage of the relatively underutilized practice of CO2 insufflation. We
      recommend that CO2 insufflation be performed in all open heart surgery cases to
      bring down the incidence of neurocognitive dysfunction. This technique is simple
      to use without any major paraphernalia or additional cost.

PMID- 25939909
TI  - Intrapulmonary teratoma: Report of a case and review of literature.
AB  - Intrapulmonary teratomas are rare tumors that are presumed to develop in
      association with mediastinal teratomas. This report describes the management of a
      rare case of a benign cystic intrapulmonary teratoma in the left upper lobe in a
      26-year-old lady, which was successfully treated by lobectomy, with no recurrence
      after 4 years of follow-up. 

PMID- 25939910
TI  - Patch closure of right aortic arch with left-sided patent ductus arteriosus.

PMID- 25939911
TI  - Intact vertebral bone lodged in right lower lobe bronchus, requiring lobectomy.

PMID- 25939912
TI  - Uncommon back pain after cardiac surgery: Left atrium deformed by huge
      osteophyte.

PMID- 25939913
TI  - Spontaneous pneumomediastinum: A complication of swine flu.
AB  - The occurrence of spontaneous pneumomediastinum in swine flu, or H1N1 influenza A
      infection, is a rare phenomenon and only few cases have been reported in
      children. We describe a case of spontaneous pneumomediastinum in adult infected
      with swine flu. 

PMID- 25939914
TI  - Comparative study of growth traits and haematological parameters of Anak and
      Nigerian heavy ecotype chickens fed with graded levels of mango seed kernel
      (Mangifera indica) meal.
AB  - One hundred fifty Anak and 120 Nigerian heavy local ecotype (NHLE) chickens were
      used to study the effects of feeding graded levels of mango seed kernel meal
      (MKM) replacing maize diet on growth traits and haematological parameters. A 2 *
      5 factorial arrangement was employed: two breeds and five diets. The birds were
      randomly allocated to five finisher diets formulated such that MKM replaced maize
      at 0, 10, 20, 30 and 40% (T1, T2, T3, T4 and T5) inclusion levels, respectively.
      The effect of breed and dietary treatments on growth performance and blood
      characteristics were determined. The results showed a significant (P < 0.05)
      breed effect on body weight and gain, shank length, thigh length, body width and
      body length. The growth traits of Anak breed were found to be superior to NHLE
      chickens. Within treatments, chicks on T1, T2 and T3, grew heavier than those on
      T4 and T5. However, feed intake, feed conversion ratio (FCR) and haematological
      indices (RBC, Hb, MCV, MCH and MCHC count) were not significant (P > 0.05) when
      the breeds and treatments were compared. It was concluded that inclusion of
      dietary MKM below 30% could replace maize in the diets of Anak and NHLE growing
      chickens without adverse effect on growth performance and blood constituents.
      This work suggests that genetic differences exist in growth traits of these
      breeds of chickens. This advantage could be useful in breed improvement
      programmes and better feeding managements of the NHLE and Anak chickens.

PMID- 25939915
TI  - Folates and aging: Role in mild cognitive impairment, dementia and depression.
AB  - In almost all tissues, including the brain, folates are required for one-carbon
      transfer reactions, which are essential for the synthesis of DNA and RNA
      nucleotides, the metabolism of amino acids and the occurrence of methylation
      reactions. The aim of this paper is to review the impact of folate status on the
      risk of development of neuropsychiatric disorders in older individuals. The
      prevalence of folate deficiency is high among individuals aged >= 65 years mainly
      due to reduced dietary intake and intestinal malabsorption. Population-based
      studies have demonstrated that a low folate status is associated with mild
      cognitive impairment, dementia (particularly Alzheimer's disease) and depression
      in healthy and neuropsychiatric diseased older individuals. The proposed
      mechanisms underlying that association include hyperhomocysteinemia, lower
      methylation reactions and tetrahydrobiopterin levels, and excessive
      misincorporation of uracil into DNA. However, currently, there is no consistent
      evidence demonstrating that folic acid supplementation improves cognitive
      function or slows cognitive decline in healthy or cognitively impaired older
      individuals. In conclusion, folate deficiency seems to be an important
      contributor for the onset and progression of neuropsychiatric diseases in the
      geriatric population but additional studies are needed in order to increase the
      knowledge of this promising, but still largely unexplored, area of research.

PMID- 25939916
TI  - Aberration-corrected STEM for atomic-resolution imaging and analysis.
AB  - Aberration-corrected scanning transmission electron microscopes are able to form
      electron beams smaller than 100 pm, which is about half the size of an average
      atom. Probing materials with such beams leads to atomic-resolution images,
      electron energy loss and energy-dispersive X-ray spectra obtained from single
      atomic columns and even single atoms, and atomic-resolution elemental maps. We
      review briefly how such electron beams came about, and show examples of
      applications. We also summarize recent developments that are propelling
      aberration-corrected scanning transmission electron microscopes in new
      directions, such as complete control of geometric aberration up to fifth order,
      and ultra-high-energy resolution EELS that is allowing vibrational spectroscopy
      to be carried out in the electron microscope. 

PMID- 25939917
TI  - Promoting graded exercise as a part of multimodal treatment in patients diagnosed
      with stress-related exhaustion.
AB  - AIMS AND OBJECTIVES: The purpose of this study was to examine, by using patient
      cohort data, the changes in exercise habits during a 12-month multimodal
      treatment period, in patients seeking specialist care for stress-related
      exhaustion. BACKGROUND: Randomised controlled trials have greatly contributed to
      the fact that both physicians and patients regard regular exercise participation
      as a highly valuable and effective treatment for mental health disorders.
      Nevertheless, little is known about the adherence to physical activity
      recommendations for patients with stress-related mental problems in a clinical
      setting. Knowledge about what can be achieved within the clinical context, and
      how current treatments can be improved, is crucial for clinicians, researchers,
      educators, managers and policy makers involved in nursing practice. DESIGN:
      Longitudinal analysis of patient cohort data. METHODS: The sample consisted of
      169 patients (79% women; mean age = 42.7 years) who were referred to a stress
      clinic due to stress-related exhaustion. All patients received multimodal
      treatment with similar components. Two different approaches to promote exercise
      were used in the clinical work (general comprehensive instruction either with or
      without an 18-week coached exercise programme). The self-reported overall
      exercise level was assessed at baseline and at three, six and 12 months after the
      first visit. Group by time effects were examined with repeated measures analyses
      of variance. RESULTS: The frequency, duration and intensity of exercise increased
      substantially during the first three months of multimodal treatment. Although
      exercise levels tended to decrease thereafter, there was still a significant time
      effect at the 12-month follow-up showing that follow-up exercise levels were
      higher than at baseline. CONCLUSION: Both general exercise instructions and
      coached exercise were effective in promoting exercise involvement. RELEVANCE TO
      CLINICAL PRACTICE: Exercise can be successfully promoted as a part of multimodal
      treatment in patients with stress-related exhaustion.

PMID- 25939920
TI  - Inducible pine rosin defense mediates interactions between an invasive insect
      fungal complex and newly acquired sympatric fungal associates.
AB  - Mutualism between insects and fungi drives insect evolutionary diversification
      and niche expansion; for invasive insects, however, mechanisms by which they
      maintain mutualistic relationships with beneficial fungi have not been clearly
      explored. Here, we report that an invasive herbivorous insect, the red turpentine
      beetle (RTB), with its co-invasive mutualistic fungus, Leptographium procerum,
      has newly acquired a set of sympatric fungi during invasion, which could
      potentially outcompete the RTB mutualistic fungus. Host pine Pinus tabuliformis
      exhibited more rosin-based responses to the sympatric fungi than to RTB
      mutualistic fungus and, in return, the rapidly induced rosin suppressed the
      sympatric fungi more significantly than L. procerum. In addition, from direct
      fungal pairing competitions, we found that the antagonistic effects of sympatric
      fungi on L. procerum were drastically reduced under induced rosin defense. Our
      results together with previous findings imply that pine oleoresin defense
      (turpentine and rosin) might have been exploited by the invasive mutualistic
      fungus L. procerum, which helps to explain its invasion success and, by
      extension, its mutualistic partner RTB in China. 

PMID- 25939918
TI  - Sepsis in the severely immunocompromised patient.
AB  - The prevention and treatment of sepsis in the immunocompromised host present a
      challenging array of diagnostic and management issues. The neutropenic patient
      has a primary defect in innate immune responses and is susceptible to
      conventional and opportunistic pathogens. The solid organ transplant patient has
      a primary defect in adaptive immunity and is susceptible to a myriad of pathogens
      that require an effective cellular immune response. Risk for infections in organ
      transplant recipients is further complicated by mechanical, vascular, and
      rejection of the transplanted organ itself. The immune suppressed state can
      modify the cardinal signs of inflammation, making accurate and rapid diagnosis of
      infection and sepsis difficult. Empiric antimicrobial agents can be lifesaving in
      these patients, but managing therapy in an era of progressive antibiotic
      resistance has become a real issue. This review discusses the challenges faced
      when treating severe infections in these high-risk patients. 

PMID- 25939919
TI  - Japanese encephalitis associated acute encephalitis syndrome cases in West
      Bengal, India: A sero-molecular evaluation in relation to clinico-pathological
      spectrum.
AB  - Japanese encephalitis (JE) is a major public health problem in Asia and worldwide
      and it is responsible mainly for viral acute encephalitis syndrome (AES). The
      sole etiologic agent of JE is Japanese encephalitis virus (JEV). Although JE/AES
      cases have been regarded traditionally as a disease of children, a growing number
      of patients with JE/AES cases are also seen in the adult age group every year in
      the state of West Bengal, India in spite of vaccination. Therefore, a systematic
      study was performed to differentiate and characterize the clinico-pathological
      parameters and viral diversity among the patients of different age groups. Viral
      diversity was also evaluated from the JE/AES cases, depending on their disease
      severity. A total of 441 JE/AES cases were included in this study. By MAC-ELISA,
      111 samples were found JEV IgM positive and among the IgM negative cases, 26
      samples were found RT-PCR positive against JEV infection. Neck rigidity, abnormal
      behavior, convulsion, protein in CSF, WBC in CSF, and aspartate transaminase in
      blood differed significantly among the patients of pediatric-adolescent and adult
      group in both IgM positive and RT-PCR positive cases. Viral diversity was
      increased significantly in the pediatric-adolescent group compared to adult
      patients. Interestingly, with the rise in disease severity the viral diversity
      was found to be increased among the patients, irrespective of their age
      distribution. Based on clinico-pathological parameters and analysis of viral
      diversity, it can be concluded that viral diversity which occurs naturally is
      likely to affect disease severity, especially in the patients of pediatric
      adolescent group.

PMID- 25939921
TI  - "Injury, illness, and work restriction in merchant seafarers".
AB  - BACKGROUND: Research on seafarer medical conditions at sea is limited. This study
      describes the frequency and distribution of seafarer injury and illness at sea,
      and explores potential risk factors for resultant lost work. MATERIALS AND
      METHODS: The study analyzed a telemedicine database of 3,921 seafarer medical
      cases between 2008 and 2011 using descriptive statistics and logistic regression.
      RESULTS: There were over twice as many illness cases (n = 2,764, 70.5%) as injury
      (n = 1,157, 29.5%) cases. Disability was more often secondary to illness (n =
      646, 54.3%), predominantly from gastrointestinal, dermatologic, and respiratory
      conditions. Logistic regression revealed age, rank, and worksite as potential
      risk factors for lost work. CONCLUSIONS: This study emphasizes illness as a
      significant problem occurring in seafarers at sea. Future research should further
      elucidate risk factors for illness, as well as injury, to inform preventive
      measures and reduce seafarer disability.

PMID- 25939933
TI  - Vitamin D Is Not as Toxic as Was Once Thought: A Historical and an Up-to-Date
      Perspective.

PMID- 25939934
TI  - Federal Regulatory Oversight of US Clinics Marketing Adipose-Derived Autologous
      Stem Cell Interventions: Insights From 3 New FDA Draft Guidance Documents.

PMID- 25939935
TI  - Changing Incidence of Serum 25-Hydroxyvitamin D Values Above 50 ng/mL: A 10-Year
      Population-Based Study.
AB  - OBJECTIVE: To determine the incidence trend of 25-hydroxyvitamin D (25(OH)D)
      values above 50 ng/mL and associated toxicity. PATIENTS AND METHODS: We conducted
      a retrospective population-based study in Olmsted County, Minnesota, in the 10
      year period from January 1, 2002, through December 31, 2011, by using the
      Rochester Epidemiology Project. Individuals were eligible if they resided in
      Olmsted County during the study period and had a measured 25(OH)D value above 50
      ng/mL. The date of the first 25(OH)D value above 50 ng/mL was considered the
      index date for incidence determination. Hypercalcemia, the primary vitamin D
      toxicity, was considered potentially associated with the 25(OH)D concentration if
      it was measured within 3 months of the 25(OH)D measurement, and such cases had a
      medical record review. RESULTS: Of 20,308 total 25(OH)D measurements, 1714
      (8.4%), 123 (0.6%), and 37 (0.2%) unique persons had 25(OH)D values above 50, 80
      and above, and 100 ng/mL and above, respectively. The age- and sex-adjusted
      incidence of 25(OH)D values above 50 ng/mL increased from 9 to 233 cases per
      100,000 person-years from 2002 to 2011 (P<.001), respectively, and was greatest
      in persons aged 65 years and older (P<.001) and in women (P<.001). Serum 25(OH)D
      values were not significantly related to serum calcium values (P=.20) or with the
      risk of hypercalcemia (P=.24). A medical record review identified 4 cases (0.2%)
      in whom 25(OH)D values above 50 ng/mL were temporally associated with
      hypercalcemia, but only 1 case had clinical toxicity associated with the highest
      observed 25(OH)D value of 364 ng/mL. CONCLUSION: The incidence of 25(OH)D values
      above 50 ng/mL increased significantly between 2002 and 2011 without a
      corresponding increase in acute clinical toxicity.

PMID- 25939937
TI  - Geriatric alcohol use disorder: a review for primary care physicians.
AB  - Alcohol use disorder in the geriatric population is a growing public health
      problem that is likely to continue to increase as the baby boomer generation
      ages. Primary care providers play a critical role in the recognition and
      management of these disorders. This concise review will focus on the prevalence,
      risk factors, screening, and clinical management of geriatric alcohol use
      disorder from a primary care perspective. 

PMID- 25939936
TI  - Hematologic characteristics of proliferative glomerulonephritides with
      nonorganized monoclonal immunoglobulin deposits.
AB  - OBJECTIVE: To study the hematologic characteristics of proliferative
      glomerulonephritides (GNs) from nonorganized glomerular monoclonal immunoglobulin
      (MIg) deposition (MIPG). PATIENTS AND METHODS: The pathology database at Mayo
      Clinic (Rochester, Minnesota) was used to find patients with MIPG who underwent a
      kidney biopsy between January 1, 2008, and December 31, 2013. Retrospective
      medical record review was conducted in the identified cohort (N=60). RESULTS: The
      median patient age was 56 years (interquartile range, 47-62 years) and the
      estimated glomerular filtration rate was 36 mL/min/1.73 m(2) (interquartile
      range, 22-52 mL/min/1.73 m(2)). Most patients had IgG MIg deposits (90%; 54 of
      60) and a membranoproliferative pattern (48%; 29 of 60). A circulating
      nephropathic MIg was detected by serum immunofixation (SIFE(+)) in 20% (12 of 59)
      and by abnormal serum free light chain ratio (sFLCR(+)) in 21% (12 of 56). The
      subsets of SIFE(+) and sFLCR(+) incompletely overlapped. The nephropathic clone
      was found by bone marrow testing (BM(+)) in 25% (10 of 40; 6 plasma cell clones
      [5 IgG; 1 IgA], 3 chronic lymphocytic leukemia [all IgG], and 1 lymphoplasmacytic
      clone [IgM]). The clone detection rate was significantly higher in patients with
      SIFE(+) (P<.001) and in those with SIFE(+) and/or sFLCR(+) (P<.001). Patients
      with SIFE(+) and BM(+) frequently had IgG1-restricted MIg deposits on renal
      biopsy immunofluorescence (P=.005). Most BM(+) patients required flow cytometry
      and immunohistochemical analysis of the marrow specimen for accurate diagnosis.
      CONCLUSION: Undetectable circulating nephropathic MIg and pathologic clones
      characterize most MIPG. Immunoglobulin isotype may predict detectability of MIg
      and clone by currently available technology. Bone marrow evaluation, including
      flow cytometry and immunohistochemical analysis, should be performed for SIFE(+)
      and/or sFLCR(+). More sensitive clone-identifying techniques in the marrow and
      extramedullary tissue are needed when SIFE and sFLCR test negative.

PMID- 25939938
TI  - 65-year-old woman with intermittent fevers, lower extremity paresthesia, weight
      loss, and malaise. Glomerulonephritis.

PMID- 25939939
TI  - National Institutes of Health: a catalyst in advancing regenerative medicine
      science into practice.
AB  - The stem cell domain of the regenerative medicine field has seen fundamental
      changes initiated by seminal discoveries in cell biology, genetic engineering,
      and whole genome sequencing. Many of these discoveries were funded in part by the
      National Institutes of Health (NIH), and the NIH remains a leader in supporting
      research in the United States. However, as the field has developed, the NIH has
      responded proactively to identify roadblocks and to develop solutions that will
      accelerate translation of basic discoveries to the clinical setting. These
      activities range from organizing specialized workshops and coordinating
      activities among international organizations and the different arms of the
      government to funding small-scale industry. In addition, the NIH has been a key
      driver in providing needed infrastructure in areas in which the private sector
      has been unable to, or does not believe it can, invest. These activities of the
      NIH are as important as its traditional funding role, and I believe they have
      contributed to the innovation and rapid pace of discovery in this field. 

PMID- 25939940
TI  - Fibromyalgia and related conditions.
AB  - Fibromyalgia is the currently preferred term for widespread musculoskeletal pain,
      typically accompanied by other symptoms such as fatigue, memory problems, and
      sleep and mood disturbances, for which no alternative cause can be identified.
      Earlier there was some doubt about whether there was an "organic basis" for these
      related conditions, but today there is irrefutable evidence from brain imaging
      and other techniques that this condition has strong biological underpinnings,
      even though psychological, social, and behavioral factors clearly play prominent
      roles in some patients. The pathophysiological hallmark is a sensitized or
      hyperactive central nervous system that leads to an increased volume control or
      gain on pain and sensory processing. This condition can occur in isolation, but
      more often it co-occurs with other conditions now being shown to have a similar
      underlying pathophysiology (eg, irritable bowel syndrome, interstitial cystitis,
      and tension headache) or as a comorbidity in individuals with diseases
      characterized by ongoing peripheral damage or inflammation (eg, autoimmune
      disorders and osteoarthritis). In the latter instance, the term centralized pain
      connotes the fact that in addition to the pain that might be caused by peripheral
      factors, there is superimposed pain augmentation occurring in the central nervous
      system. It is important to recognize this phenomenon (regardless of what term is
      used to describe it) because individuals with centralized pain do not respond
      nearly as well to treatments that work well for peripheral pain (surgery and
      opioids) and preferentially respond to centrally acting analgesics and
      nonpharmacological therapies. 

PMID- 25939941
TI  - Epigenetics and childhood obesity.

PMID- 25939942
TI  - In reply--Epigenetics and Childhood Obesity.

PMID- 25939943
TI  - Continued caution recommended in use of intravenous iron preparations.

PMID- 25939944
TI  - Familial transient global amnesia.

PMID- 25939945
TI  - In reply--Continued Caution Recommended in Use of Intravenous Iron Preparations.

PMID- 25939946
TI  - In reply--Familial Transient Global Amnesia.

PMID- 25939947
TI  - Dissatisfaction as a unifying force for social action.

PMID- 25939948
TI  - In reply--Dissatisfaction as a Unifying Force for Social Action.

PMID- 25939949
TI  - Brown tumors: severe osteitis fibrosa cystica.

PMID- 25939950
TI  - 67-year-old man with dyspnea and hemoptysis. Diffuse alveolar hemorrhage (DAH).

PMID- 25939952
TI  - FTY720 induces autophagy-related apoptosis and necroptosis in human glioblastoma
      cells.
AB  - FTY720 is a potent immunosuppressant which has preclinical antitumor efficacy in
      various cancer models. However, its role in glioblastoma remains unclear. In the
      present study, we found that FTY720 induced extrinsic apoptosis, necroptosis and
      autophagy in human glioblastoma cells. Inhibition of autophagy by either RNA
      interference or chemical inhibitors attenuated FTY720-induced apoptosis and
      necrosis. Furthermore, autophagy, apoptosis and necrosis induction were dependent
      on reactive oxygen species-c-Jun N-terminal kinase-protein 53 (ROS-JNK-p53) loop
      mediated phosphatidylinositide 3-kinases/protein kinase B/mammalian target of
      rapamycin/p70S6 kinase (PI3K/AKT/mTOR/p70S6K) pathway. In addition, receptor
      interacting protein 1 and 3 (RIP1 and RIP3) served as an upstream of ROS-JNK-p53
      loop. However, the phosphorylation form of FTY720 induced autophagy but not
      apoptosis and necroptosis. Finally, the in vitro results were validated in vivo
      in xenograft mouse of glioblastoma cells. In conclusion, the current study
      provided novel insights into understanding the mechanisms and functions of FTY720
      induced apoptosis, necroptosis and autophagy in human glioblastoma cells. 

PMID- 25939953
TI  - Efficacy and Safety of Recombinant Factor VII as Rescue for Severe Perioperative
      Bleeding in HeartMate II Recipients.
AB  - INTRODUCTION: We aimed to study the efficacy and safety of recombinant factor
      VIIa (rFVIIa) for management of perioperative bleeding in HeartMate II
      recipients. MATERIALS AND METHODS: Fifty-seven patients underwent HeartMate II
      implantation. Sixteen patients received rFVIIa (six intraop, eight early postop,
      and two both intra- and postop). The effect of rFVIIa on transfusion of blood
      products as well as the amount of chest tube drainage was used to assess efficacy
      and 30-day incidence of thromboembolic events was used to assess safety. RESULTS:
      Patients who received intraoperative rFVIIa had been transfused significantly
      more blood products prior to rFVIIa administration compared to total amount of
      intraoperatively transfused blood products in those who did not receive intra-op
      rFVIIa; however, there were no significant differences in the amount of
      transfused blood products and chest tube output in the 24-hour postoperative
      period between the two groups. Postoperative administration of rFVIIa did not
      have a significant impact on the amount of red blood cell transfusion but there
      was a trend towards decreased requirement for fresh frozen plasma (mean 2.7 vs.
      1.1, p = 0.08), platelet (1.5 vs. 0.7, p = 0.14), and cryoprecipitate (5.3 vs.
      1.2, p = 0.09). The hourly rate of chest tube output also decreased significantly
      from an average of 235 +/- 57 mL/hour prior to rFVIIa administration to an
      average of 98 +/- 36 mL/hour in the first four hours after rFVIIa administration
      (p value = 0.003). There were no 30-day thromboembolic events in those patients
      who received rFVIIa. CONCLUSIONS: This study supports selective use of rFVIIa in
      HeartMate II recipients for the management of severe perioperative bleeding.

PMID- 25939954
TI  - Breast: Sezary Syndrome: A Unique Presentation.
AB  - Sezary syndrome is a subtype of cutaneous T cell lymphoma which usually presents
      as generalized skin disease with erytheroderma. Distal organ involvement is rare
      and is usually a late finding in the course of the disease. Breast involvement is
      extremely rare. Herein, we present a case report of a patient whose initial
      presentation involved an intramammary lymph node prior to the onset of more
      characteristic skin disease. Sezary syndrome was confirmed by cythopathologic
      findings. 

PMID- 25939955
TI  - The meaning of leisure for children and young people with physical disabilities:
      a systematic evidence synthesis.
AB  - AIM: Participation in leisure has known health benefits. Children and young
      people (CYP) with physical disabilities demonstrate reduced participation in
      leisure. To facilitate their meaningful participation, one must understand what
      leisure means to CYP. The aim of this study was to systematically synthesize
      evidence from qualitative studies on the meaning of leisure for CYP with physical
      disabilities. METHODS: CINAHL, MEDLINE, AMED, EMBASE, PsycINFO, and ERIC were
      searched periodically from January 2012 until May 2013. Qualitative studies
      reporting the views of CYP (0-18y) with physical disabilities on leisure
      participation were included. The analysis involved thematic syntheses, double
      coding, and established quality appraisal procedures. RESULTS: Twelve studies met
      inclusion criteria, addressing the leisure experiences of 146 CYP with
      disabilities. Four themes core to the meaning of leisure for these CYP were (1)
      'fun': the enjoyment and pleasure experienced from leisure; (2) 'freedom' of
      choice and from constraints; (3) 'fulfilment': discovering, developing, and
      displaying potential; and (4) 'friendship': social connectedness and belonging.
      INTERPRETATION: The identified themes resonate with the psychological needs
      outlined by self-determination theory: fun relates to satisfaction and intrinsic
      motivation; freedom relates to 'autonomy'; fulfilment relates to a belief in
      'competence'; and friendship resonates with 'relatedness'. Social context had an
      impact on all of these themes, indicating that this is an important target for
      leisure participation interventions.

PMID- 25939956
TI  - NaV3O8 nanosheet@polypyrrole core-shell composites with good electrochemical
      performance as cathodes for Na-ion batteries.
AB  - Novel NaV3O8 nanosheet@polypyrrole core-shell composites have been successfully
      prepared for the first time via a chemical oxidative polymerization method. Based
      on the morphological and microstructural characterization, it was found that
      polypyrrole (PPy) was uniformly wrapped on the surfaces of the NaV3O8 nanosheets.
      When used as a cathode for Na-ion batteries, the as-synthesized NaV3O8@10% PPy
      composite showed significantly improved cycling performance (with a discharge
      capacity of 99 mA h g(-1) after 60 cycles at 80 mA g(-1)) and better rate
      capacity (with a discharge capacity of 63 mA h g(-1) at a high current density of
      640 mA g(-1)) than pristine NaV3O8 nanosheets. The greatly enhanced performance
      benefits from the unique core-shell structure, where the PPy coating not only
      prevents the pulverization and aggregation of the lamellar NaV3O8 nanosheets
      during cycling, which can improve the cycling stability, but also enhances the
      electrical conductivity of the composite, which can facilitate Na(+) ion
      diffusion. 

PMID- 25939957
TI  - The Streptococcus pyogenes orphan protein tyrosine phosphatase, SP-PTP, possesses
      dual specificity and essential virulence regulatory functions.
AB  - Group A Streptococcus (GAS) is a human pathogen that causes high morbidity and
      mortality. GAS lacks a gene encoding tyrosine kinase but contains one encoding
      tyrosine phosphatase (SP-PTP). Thus, GAS is thought to lack tyrosine
      phosphorylation, and the physiological significance of SP-PTP is, therefore,
      questionable. Here, we demonstrate that SP-PTP possesses dual phosphatase
      specificity for Tyr- and Ser/Thr-phosphorylated GAS proteins, such as Ser/Thr
      kinase (SP-STK) and the SP-STK-phosphorylated CovR and WalR proteins. Phenotypic
      analysis of GAS mutants lacking SP-PTP revealed that the phosphatase activity per
      se positively regulates growth, cell division and the ability to adhere to and
      invade host cells. Furthermore, A549 human lung cells infected with GAS mutants
      lacking SP-PTP displayed increased Ser-/Thr-/Tyr-phosphorylation. SP-PTP also
      differentially regulates the expression of ~50% of the total GAS genes, including
      several virulence genes potentially through the two-component regulators, CovR,
      WalR and PTS/HPr regulation of Mga. Although these mutants exhibit attenuated
      virulence, a GAS mutant overexpressing SP-PTP is hypervirulent. Our study
      provides the first definitive evidence for the presence and importance of Tyr
      phosphorylation in GAS and the relevance of SP-PTP as an important therapeutic
      target. 

PMID- 25939958
TI  - Oral Cyclosporine Weekend Therapy: A New Maintenance Therapeutic Option in
      Patients with Severe Atopic Dermatitis.
AB  - Cyclosporine A (CyA) is a systemic therapy used to control severe atopic
      dermatitis (AD) in children, but its use may be associated with serious side
      effects. Intermittent short-course therapy has been used to minimize these risks
      without the loss of clinical benefits. We conducted a 20-week study using
      intermittent short-course CyA therapy in five patients with severe AD and a
      Scoring Atopic Dermatitis (SCORAD) score >40. The result was a reduction in the
      cumulative dose of CyA and serum CyA level, which allows for a longer duration of
      CyA treatment and decreases the risk of relapse in patients with severe AD. 

PMID- 25939959
TI  - Transformation of graphene oxide by ferrous iron: Environmental implications.
AB  - Abiotic transformation of graphene oxide (GO) in aquatic environments can
      markedly affect the fate, transport, and effects of GO. The authors observed that
      ferrous iron (Fe[II])-an environmentally abundant, mild reductant-can
      significantly affect the physicochemical properties of GO (examined by treating
      aqueous GO suspensions with Fe(2+) at room temperature, with doses of 0.032 mM
      Fe(2+)  per mg/L, 0.08 mM Fe(2+)  per mg/L, and 0.32 mM Fe(2+)  per mg/L GO).
      Microscopy data showed stacking of GO nanosheets on Fe(2+) treatment.
      Spectroscopy evidence (X-ray diffraction, Fourier transform infrared
      transmission, Raman and X-ray photoelectron spectroscopy) showed significant
      changes in GO surface O-functionalities, in terms of loss of epoxy and carbonyl
      groups but increase of carboxyl group. The reduction mechanisms were verified by
      treating model organic molecules (styrene oxide, p-benzoquinone, and benzoic
      acid) resembling O-containing fragments of GO macromolecules with Fe(2+). With
      sedimentation and adsorption experiments (using bisphenol A as a model
      contaminant), the authors demonstrated that Fe(2+) reduced GOs still maintained
      relatively high colloidal stability, whereas their adsorption affinities were
      significantly enhanced. Thus, reduction of GO by mild reductants might be of
      greater environmental concerns than by stronger reducing agents (e.g., N2H4 and
      S(2-)), because the latter can result in too significant losses of surface O
      functionalities and colloidal stability of GO. This interesting aspect should be
      given consideration in the risk assessment of GO.

PMID- 25939960
TI  - Dimensional soft tissue changes following soft tissue grafting in conjunction
      with implant placement or around present dental implants: a systematic review.
AB  - OBJECTIVES: To systematically review changes in mucosal soft tissue thickness and
      keratinised mucosa width after soft tissue grafting around dental implants.
      MATERIALS AND METHODS: An electronic literature search was conducted of the
      MEDLINE database published between 2009 and 2014. Sequential screenings at the
      title, abstract, and full-text levels were performed. Clinical human studies in
      the English language that had reported changes in soft tissue thickness or
      keratinised mucosa width after soft tissue grafting at implant placement or
      around a present implant at 6-month follow-up or longer were included. RESULTS:
      The search resulted in fourteen articles meeting the inclusion criteria: Six of
      them reported connective tissue grafting around present dental implants, compared
      to eight at the time of implant placement. Better long-term soft tissue thickness
      outcomes were reported for soft tissue augmentation around dental implants (0.8
      1.4 mm), compared with augmentation at implant placement (-0.25-1.43 mm). Both
      techniques were effective in increasing keratinised tissue width: at implant
      placement (2.5 mm) or around present dental implants (2.33-2.57 mm). CONCLUSIONS:
      The present systematic review discovered that connective tissue grafts enhanced
      keratinised mucosa width and soft tissue thickness for an observation period of
      up to 48 months. However, some shrinkage may occur, resulting in decreases in
      soft tissue, mostly for the first three months. Further investigations using
      accurate evaluation methods need to be done to evaluate the appropriate time for
      grafting.

PMID- 25939961
TI  - Conscientiousness, openness to experience and extraversion as predictors of
      nursing work performance: a facet-level analysis.
AB  - AIM: This study examined the relationships between the personality traits of
      conscientiousness, openness and extraversion at trait and facet-levels and three
      indicators of work role performance; proficiency, 'adaptivity' and proactivity
      measured at individual, team and organisational levels. BACKGROUND: This is one
      of the first studies to explore the relationship between personality, measured at
      trait and facet-level and performance using a comprehensive range of performance
      indicators. METHOD: An online survey of 393 nurses from health-care organisations
      across Australia was conducted to test hypothesised relationships. RESULTS: Path
      analyses revealed numerous relationships between personality, measured at both
      trait and facet-levels, and work role performance. Conscientiousness was
      highlighted as the strongest driver of work role performance across all the
      indicators, with extraversion also strongly associated with work role
      performance. Openness to experience, previously considered a week predictor of
      performance, was, when examined at the facet-level, related to all of the work
      role performance indicators. CONCLUSIONS: Results suggests a bandwidth effect,
      where the personality traits drive global performance while the facets drive
      specific performance. IMPLICATIONS FOR NURSING MANAGEMENT: Better understanding
      of the relationship between personality and work role performance will help nurse
      managers to foster the fit between individual and organisation, improving job
      satisfaction, engagement, retention and performance in role.

PMID- 25939962
TI  - Treatment of an adolescent with chronic myeloid leukemia and the T315I mutation
      with ponatinib.

PMID- 25939963
TI  - Coordination properties of a metal chelator clioquinol to Zn(2+) studied by
      static DFT and ab initio molecular dynamics.
AB  - Several lines of evidence supporting the role of metal ions in amyloid
      aggregation, one of the hallmarks of Alzheimer's disease (AD), have turned metal
      ion chelation into a promising therapeutic treatment. The design of efficient
      chelating ligands requires proper knowledge of the electronic and molecular
      structure of the complexes formed, including their hydration properties. Among
      various potential chelators, clioquinol (5-chloro-7-iodo-8-hydroxyquinoline, CQH)
      has been evaluated with relative success in in vitro experiments and even in
      phase 2 clinical trials. Clioquinol interacts with Zn(ii) to lead to a binary
      metal/ligand 1 : 2 stoichiometric complex in which the phenolic group of CQH is
      deprotonated, resulting in Zn(CQ)2 neutral complexes, to which additional water
      molecules may coordinate. In the present work, the coordinative properties of
      clioquinol in aqueous solution have been analyzed by means of static, minimal
      cluster based DFT calculations and explicit solvent ab initio molecular dynamics
      simulations. Results from static calculations accounting for solvent effects by
      means of polarized continuum models suggest that the preferred metal coordination
      environment is tetrahedral Zn(CQ)2, whereas ab initio molecular dynamics
      simulations point to quasi degenerate penta Zn(CQ)2(H2O) and hexa Zn(CQ)2(H2O)2
      coordinated complexes. The possible reasons for these discrepant results are
      discussed. 

PMID- 25939964
TI  - Acute Lateral Myocardial Infarction Secondary to Tramadol-Induced Kounis
      Syndrome.

PMID- 25939965
TI  - Analysis of Complaints from Patients During Mechanical Ventilation After Cardiac
      Surgery: A Retrospective Study.
AB  - OBJECTIVES: This study analyzed major complaints from patients during mechanical
      ventilation after cardiac surgery and identified the most common complaints to
      reduce adverse psychologic responses. DESIGN: Retrospective. SETTING: A single
      tertiary university hospital. PARTICIPANTS: Patients with heart disease who were
      on mechanical ventilation after cardiac surgery (N = 800). INTERVENTIONS: The
      major complaints of the patients during mechanical ventilation after cardiac
      surgery were analyzed. MEASUREMENTS AND MAIN RESULTS: Patients' comfort was
      evaluated using a visual analog scale, and the factors affecting comfort were
      analyzed. The average visual analog scale score in all patients was 5.8+/-2.0,
      and most patients presented moderate discomfort. The factors affecting comfort
      included dry mouth, thirst, tracheal intubation, aspiration of sputum,
      communication barriers, limited mobility, fear/anxiety, patient-ventilator
      dyssynchrony, and poor environmental conditions. Of these factors, 8 were
      independent predictors of the visual analog scale score. Patients considered
      mechanical ventilation to be the worst part of their hospitalization.
      CONCLUSIONS: The study identified 8 independent factors causing discomfort in
      patients during mechanical ventilation after cardiac surgery. Clinicians should
      take appropriate measures and implement nursing interventions to reduce
      suffering, physical and psychologic trauma, and adverse psychologic responses and
      to promote recovery.

PMID- 25939966
TI  - Can Intraoperative Transesophageal Echocardiography Predict Postoperative Aortic
      Insufficiency in Patients Receiving Implantable Left Ventricular Assist Devices?
AB  - OBJECTIVE: Aortic insufficiency (AI) develops in 25% of patients after left
      ventricular assist device (LVAD) insertion. The objective of this study was to
      evaluate the occurrence of new-onset AI upon initiation of cardiopulmonary bypass
      (CPB) required for LVAD insertion and the potential ability of this new-onset AI
      to predict development of post-LVAD insertion AI. DESIGN: Forty-one patients
      undergoing LVAD insertion were studied. Intraoperative transesophageal
      echocardiography (TEE) evaluation was performed at baseline (post-induction, pre
      sternotomy), 5 minutes after CPB initiation, and post-chest closure. Patients
      were followed up postoperatively for development of AI. SETTING: Single
      university hospital. PARTICIPANTS: Patients undergoing elective LVAD insertion.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: At baseline, 35 patients
      exhibited none-trace AI, 4 exhibited mild AI, 2 exhibited moderate AI, and none
      exhibited severe AI. After initiation of CPB, 34 patients exhibited no change in
      degree of AI yet 7 exhibited an increase in AI severity. However, all 7 patients
      exhibited no change in degree of AI at chest closure and one exhibited a decrease
      in AI severity. Four patients developed at least moderate AI during the
      postoperative period (range 3-8 months). However, only one of these patients
      exhibited an increase in AI severity after initiation of CPB for LVAD insertion.
      No significant changes in aortic root measurements were observed during the
      entire intraoperative period (within patients nor between patients with/without
      development of at least moderate postoperative AI). CONCLUSIONS: One in 5
      patients undergoing LVAD insertion will demonstrate an increase in AI severity at
      CPB initiation without changes in aortic root measurements. None of the
      information obtained from intraoperative TEE seemed to predict development of at
      least moderate postoperative AI.

PMID- 25939967
TI  - Methylresorcinarene: a reaction vessel to control the coordination geometry of
      copper(II) in pyridine N-oxide copper(II) complexes.
AB  - Pyridine and 2-picolinic acid N-oxides form 2 : 2 and 2 : 1 ligand : metal (L :
      M) discrete L2M2 and polymeric complexes with CuCl2 and Cu(NO3)2, respectively,
      with copper(ii) salts. The N-oxides also form 1 : 1 host-guest complexes with
      methylresorcinarene. In combination, the three components form a unique 2 : 2 : 1
      host-ligand-metal complex. The methylresorcinarene acts as a reaction
      vessel/protecting group to control the coordination of copper(ii) from cis-see
      saw to trans-square planar, and from octahedral to square planar coordination
      geometry. These processes were studied in solution and in the solid state via(1)H
      NMR spectroscopy and single crystal X-ray diffraction. 

PMID- 25939968
TI  - High-power multi-megahertz source of waveform-stabilized few-cycle light.
AB  - Waveform-stabilized laser pulses have revolutionized the exploration of the
      electronic structure and dynamics of matter by serving as the technological basis
      for frequency-comb and attosecond spectroscopy. Their primary sources, mode
      locked titanium-doped sapphire lasers and erbium/ytterbium-doped fibre lasers,
      deliver pulses with several nanojoules energy, which is insufficient for many
      important applications. Here we present the waveform-stabilized light source that
      is scalable to microjoule energy levels at the full (megahertz) repetition rate
      of the laser oscillator. A diode-pumped Kerr-lens-mode-locked Yb:YAG thin-disk
      laser combined with extracavity pulse compression yields waveform-stabilized few
      cycle pulses (7.7 fs, 2.2 cycles) with a pulse energy of 0.15 MUJ and an average
      power of 6 W. The demonstrated concept is scalable to pulse energies of several
      microjoules and near-gigawatt peak powers. The generation of attosecond pulses at
      the full repetition rate of the oscillator comes into reach. The presented system
      could serve as a primary source for frequency combs in the mid infrared and
      vacuum UV with unprecedented high power levels. 

PMID- 25939969
TI  - Facile and sustainable synthesis of shaped iron oxide nanoparticles: effect of
      iron precursor salts on the shapes of iron oxides.
AB  - A facile and sustainable protocol for synthesis of six different shaped iron
      oxides is developed. Notably, all the six shapes of iron oxides can be
      synthesised using exactly same synthetic protocol, by simply changing the
      precursor iron salts. Several of the synthesised shapes are not reported before.
      This novel protocol is relatively easy to implement and could contribute to
      overcome the challenge of obtaining various shaped iron oxides in economical and
      sustainable manner. 

PMID- 25939970
TI  - Laser arytenoidectomy and posterior cordotomy in a patient with bilateral vocal
      cord paralysis due to multiple system atrophy.
AB  - Bilateral vocal cord paralysis leading to stridor is a known but rare
      complication of Parkinson's disease (PD) and a recognised complication of
      multiple system atrophy (MSA). Tracheostomy is a commonly offered treatment,
      leading to substantial adaptations and lifestyle changes for the patient.
      Patients can struggle to manage a tracheostomy due to the tremor and bradykinesia
      associated with their parkinsonism. We report a case of bilateral vocal cord
      paralysis leading to significant stridor in a patient with atypical parkinsonism
      (probable MSA). To avoid tracheostomy, our patient underwent successful right
      sided laser arytenoidectomy and posterior cordotomy as a day-case procedure. At
      follow-up, he had a weaker voice but complete recovery from the shortness of
      breath and stridor. He was very satisfied with the outcome. We conclude that,
      despite resulting in a weaker voice, this procedure offers an option to the
      patient that improves quality of life. 

PMID- 25939971
TI  - Hepatic portal venous gas and portal venous thrombosis following colonoscopy in a
      patient with terminal ileal Crohn's disease.
AB  - A 27-year-old man developed extensive hepatic portal venous gas (HPVG) shortly
      after staging colonoscopy for active, ulcerating, terminal ileal Crohn's disease.
      Non-operative management was instigated with broad-spectrum antibiotics and
      thromboprophylaxis. Radiology at 72 h demonstrated resolution of HPVG but
      revealed fresh non-occlusive left portal vein thrombus. Anticoagulation with
      warfarin was continued for 1 year, during which the thrombus initially progressed
      and then organised with recanalisation of the portal vein. There were no long
      term clinical consequences. HPVG has previously been documented as a rare
      complication of inflammatory bowel disease and endoscopic intervention. We
      hypothesise that the barotrauma sustained during endoscopy, in association with
      active ulceration and mucosal friability, predisposes to the influx of gas and
      bacteria into the portal system. We describe successful non-operative management
      of HPVG in this setting and draw attention to an additional complication of
      portal venous thrombosis, highlighting the importance of thromboprophylaxis and
      serial radiological examination. 

PMID- 25939972
TI  - Spotted bone disease.

PMID- 25939973
TI  - Paraneoplastic encephalopathy: an unusual presenting feature of bladder cancer
      metastasis.
AB  - A 73-year-old woman with a history of localised transitional cell cancer (TCC) of
      the bladder, resected 22 years prior, presented with tremor, gait unsteadiness
      and cognitive deficits. Basic neurological workup was negative and CT of the
      abdomen revealed recurrent TCC with a solitary pelvic metastasis. She was treated
      with surgical resection of her tumour and immunosuppression. Her symptoms
      resolved, and it was felt her presentation was consistent with paraneoplastic
      encephalopathy in the setting of bladder cancer metastasis. She has remained
      disease and symptom free over 5 years of follow-up. This case report reviews the
      mechanism, clinical features and treatment of paraneoplastic neurological
      syndromes, and discusses briefly the management of oligometastatic recurrent
      bladder cancer. 

PMID- 25939974
TI  - Chest pain in the recovery room, following topical intranasal cocaine solution
      use.
AB  - On awakening in the recovery room after a general anaesthetic for ear, nose and
      throat surgery, a 28-year-old woman reported central chest pain. She had received
      topical nasal cocaine solution preoperatively. She required intravenous opioids
      and sublingual glyceryl trinitrate before the pain settled. There was no evidence
      of significant myocardial injury and the patient was discharged later that day.
      The use of topical nasal cocaine solution in anaesthesia and its adverse
      myocardial effects are discussed. 

PMID- 25939975
TI  - Diffuse large B-cell lymphoma in the psoas muscle.

PMID- 25939976
TI  - Protective effect of sulfurous water in peripheral blood mononuclear cells of
      Alzheimer's disease patients.
AB  - AIMS: One of the main features of sulfurous water (SW) is the presence of
      hydrogen sulfide (H2S), which confers its antioxidant activity. Since oxidative
      stress plays an important role in Alzheimer's disease (AD) we hypothesize that SW
      could have a protective effect in these patients. MATERIAL AND METHODS: A
      therapeutic in vitro approach of SW was performed in peripheral blood mononuclear
      cells (PBMCs) of AD patients and in age-matched healthy non-demented controls
      using one modification of the comet assay (to measure oxidative DNA damage) and
      the MTT assay (as an indicator of cell viability). Hydrogen peroxide and
      homocysteine were used to induce oxidative DNA damage, and vitamin C, Trolox and
      N-acetyl-cysteine were selected as antioxidants of reference to compare SW
      treatment results. KEY FINDINGS: SW did not increase per se the oxidative DNA
      damage of PBMC. Furthermore, SW protected them against enhanced oxidative stress
      in AD and control populations after pro-oxidant stimuli, with similar results to
      those observed when using the antioxidants of reference. Nevertheless, SW was the
      only treatment that could avoid the loss of viability of PBMC for all pro-oxidant
      stimuli in both populations, suggesting that H2S could confer to SW a more
      antioxidant capacity than other known antioxidants. SIGNIFICANCE: The protective
      effect of SW was proved for the first time not only in DNA stability but also in
      cell viability preservation in AD, indicating that further research in other in
      vitro and in vivo models could lead to include SW as a possible therapy for AD.

PMID- 25939978
TI  - Age of acquisition and imageability norms for base and morphologically complex
      words in English and in Spanish.
AB  - The extent to which processing words involves breaking them down into smaller
      units or morphemes or is the result of an interactive activation of other units,
      such as meanings, letters, and sounds (e.g., dis-agree-ment vs. disagreement), is
      currently under debate. Disentangling morphology from phonology and semantics is
      often a methodological challenge, because orthogonal manipulations are difficult
      to achieve (e.g., semantically unrelated words are often phonologically related:
      casual-casualty and, vice versa, sign-signal). The present norms provide a
      morphological classification of 3,263 suffixed derived words from two widely
      spoken languages: English (2,204 words) and Spanish (1,059 words).
      Morphologically complex words were sorted into four categories according to the
      nature of their relationship with the base word: phonologically transparent
      (friend-friendly), phonologically opaque (child-children), semantically
      transparent (habit-habitual), and semantically opaque (event-eventual). In
      addition, ratings were gathered for age of acquisition, imageability, and
      semantic distance (i.e., the extent to which the meaning of the complex derived
      form could be drawn from the meaning of its base constituents). The norms were
      completed by adding values for word frequency; word length in number of phonemes,
      letters, and syllables; lexical similarity, as measured by the number of
      neighbors; and morphological family size. A series of comparative analyses from
      the collated ratings for the base and derived words were also carried out. The
      results are discussed in relation to recent findings. 

PMID- 25939977
TI  - KU675, a Concomitant Heat-Shock Protein Inhibitor of Hsp90 and Hsc70 that
      Manifests Isoform Selectivity for Hsp90alpha in Prostate Cancer Cells.
AB  - The 90-kDa heat-shock protein (Hsp90) assists in the proper folding of numerous
      mutated or overexpressed signal transduction proteins that are involved in
      cancer. Inhibiting Hsp90 consequently is an attractive strategy for cancer
      therapy as the concomitant degradation of multiple oncoproteins may lead to
      effective antineoplastic agents. Here we report a novel C-terminal Hsp90
      inhibitor, designated KU675, that exhibits potent antiproliferative and cytotoxic
      activity along with client protein degradation without induction of the heat
      shock response in both androgen-dependent and -independent prostate cancer cell
      lines. In addition, KU675 demonstrates direct inhibition of Hsp90 complexes as
      measured by the inhibition of luciferase refolding in prostate cancer cells. In
      direct binding studies, the internal fluorescence signal of KU675 was used to
      determine the binding affinity of KU675 to recombinant Hsp90alpha, Hsp90beta, and
      Hsc70 proteins. The binding affinity (Kd) for Hsp90alpha was determined to be 191
      MUM, whereas the Kd for Hsp90beta was 726 MUM, demonstrating a preference for
      Hsp90alpha. Western blot experiments with four different prostate cancer cell
      lines treated with KU675 supported this selectivity by inducing the degradation
      of Hsp90alpha -: dependent client proteins. KU675 also displayed binding to Hsc70
      with a Kd value at 76.3 MUM, which was supported in cellular by lower levels of
      Hsc70-specific client proteins on Western blot analyses. Overall, these findings
      suggest that KU675 is an Hsp90 C-terminal inhibitor, as well as a dual inhibitor
      of Hsc70, and may have potential use for the treatment of cancer.

PMID- 25939979
TI  - Multiple imputation of missing covariate values in multilevel models with random
      slopes: a cautionary note.
AB  - Multiple imputation (MI) has become one of the main procedures used to treat
      missing data, but the guidelines from the methodological literature are not
      easily transferred to multilevel research. For models including random slopes,
      proper MI can be difficult, especially when the covariate values are partially
      missing. In the present article, we discuss applications of MI in multilevel
      random-coefficient models, theoretical challenges posed by slope variation, and
      the current limitations of standard MI software. Our findings from three
      simulation studies suggest that (a) MI is able to recover most parameters, but is
      currently not well suited to capture slope variation entirely when covariate
      values are missing; (b) MI offers reasonable estimates for most parameters, even
      in smaller samples or when its assumptions are not met; and

PMID- 25939980
TI  - Orthodontic scanners: what's available?
AB  - The popularity and availability of virtual technology in orthodontics for the
      replacement of hard-copy records with electronic records is growing rapidly, with
      a move towards a 'digital' patient for diagnosis, treatment planning, monitoring
      of treatment progress and outcome. As part of this ongoing development, three
      dimensional digital models of the dental arches have the potential to replace
      traditional plaster models and their associated limitations for treatment
      planning, appliance construction and simulated treatment outcomes. This article
      provides the reader with a summary of the currently available benchtop model
      scanners and intraoral scanners. It is likely that this technology will become
      increasingly common-place within the orthodontic profession over the next decade.

PMID- 25939981
TI  - Effects of extremely low-frequency electromagnetic fields (ELF-EMF) exposure on
      B6C3F1 mice.
AB  - OBJECTIVE: Long-term exposure study was conducted to investigate the effects of
      extremely low-frequency electromagnetic field on the tumor promotion process and
      fertility. METHODS: Ten pregnant C57BL/6NCrj mice were exposed to 50 Hz field 500
      mG for 1 week (12 h per day), and 24 male and 42 female B6C3F1mice born from them
      were further exposed up to 15.5 months. As a control group, 10 pregnant mice were
      bred without exposure, and 30 produced male and 32 female mice were observed
      without exposure for the same period. RESULTS: Mean body weights of exposed
      groups of male and female mice were decreased significantly than those of the
      control groups. In exposed mice, there was no increased incidence of liver and
      lung tumor. In female mice, the incidence of chronic myeloid leukemia [3/42 (7%)]
      in the exposed group was significantly greater than in the control group. The
      size of seminiferous tubules in the EMF exposed groups were significantly less
      than the control group. CONCLUSIONS: These data support the hypothesis that long
      term exposure of 50 Hz magnetic fields is a significant risk factor for
      neoplastic development and fertility in mice.

PMID- 25939982
TI  - Training of neonatal cardiopulmonary resuscitation instructors.
AB  - BACKGROUND: The Consensus on Science and Treatment Recommendations 2010 supported
      simulation-based training for education in resuscitation. This approach has been
      introduced into neonatal cardiopulmonary resuscitation (NCPR) courses in Japan,
      but no method for teaching instructors has been established. We developed a
      course for training instructors of NCPR, with inclusion of an instruction
      practice program. The goal of the study was to evaluate the performance of
      instructors who completed the course. METHODS: Based on problems in the
      conventional instructor training course (old course 1), we developed and
      implemented a new course. Persons who had completed an NCPR course took the new
      course after developing two resuscitation scenarios. The new course included
      lectures and instruction practice, in which participants provided instruction
      using these scenarios. Instruction by participants was evaluated, and knowledge,
      opinions and satisfaction were examined by questionnaire after the course.
      Activity of the participants as instructors for 6 months after certification was
      also evaluated. The performance of trained instructors was compared between the
      old and new courses. RESULTS: Of 143 participants in the new course, > 90% had
      confidence to teach NCPR, while only 50-60% of the 89 participants in the old
      course indicated that they could instruct on resuscitation procedures and
      practice (P < 0.001). All participants in the new course recognized the value of
      scenario practice and all were glad they had taken the course. For 6 months after
      certification, significantly more participants who had done the new course worked
      as instructors compared with those who had done the old course (60% vs 34%, P <
      0.001). CONCLUSION: This is the first trial of a resuscitation training course
      using scenarios that participants developed themselves. A new course including
      instruction practice for training NCPR instructors was effective for improving
      instructor performance.

PMID- 25939983
TI  - Dermocystidium-like organism linked with a mortality event in yellow perch Perca
      flavescens (Mitchill) in Ontario, Canada.

PMID- 25939985
TI  - Spiroboronate Si-rhodamine as a near-infrared probe for imaging lysosomes based
      on the reversible ring-opening process.
AB  - A cyclic boronate structure was incorporated into Si-rhodamine to design a pH
      activatable near-infrared (NIR) probe based on the reversible ring-opening
      process triggered by H(+). The probe showed general suitability of specific
      labelling of acidic lysosomes and tracking their pH changes in living cells. 

PMID- 25939984
TI  - Mechanisms of transfer of bioactive molecules through the cell membrane by
      electroporation.
AB  - A short review of biophysical mechanisms for electrotransfer of bioactive
      molecules through the cell membrane by using electroporation is presented. The
      concept of transient hydrophilic aqueous pores and membrane electroporation
      mechanisms of single cells and cells in suspension models are analyzed. Alongside
      the theoretical approach, some peculiarities of drug and gene electrotransfer
      into cells and applications in clinical trials are discussed.

PMID- 25939986
TI  - Modulation of stratum corneum lipid composition and organization of human skin
      equivalents by specific medium supplements.
AB  - Our in-house human skin equivalents contain all stratum corneum (SC) barrier
      lipid classes, but have a reduced level of free fatty acids (FAs), of which a
      part is mono-unsaturated. These differences lead to an altered SC lipid
      organization and thereby a reduced barrier function compared to human skin. In
      this study, we aimed to improve the SC FA composition and, consequently, the SC
      lipid organization of the Leiden epidermal model (LEM) by specific medium
      supplements. The standard FA mixture (consisting of palmitic, linoleic and
      arachidonic acids) supplemented to the medium was modified, by replacing
      protonated palmitic acid with deuterated palmitic acid or by the addition of
      deuterated arachidic acid to the mixture, to determine whether FAs are taken up
      from the medium and are incorporated into SC of LEM. Furthermore, supplementation
      of the total FA mixture or that of palmitic acid alone was increased four times
      to examine whether this improves the SC FA composition and lipid organization of
      LEM. The results demonstrate that the deuterated FAs are taken up into LEMs and
      are subsequently elongated and incorporated in their SC. However, a fourfold
      increase in palmitic acid supplementation does not change the SC FA composition
      or lipid organization of LEM. Increasing the concentration of the total FA
      mixture in the medium resulted in a decreased level of very long chain FAs and an
      increased level of mono-unsaturated FAs, which lead to deteriorated SC lipid
      properties. These results indicate that SC lipid properties can be modulated by
      specific medium supplements. 

PMID- 25939987
TI  - Clinical and multimodal imaging characteristics of acute Vogt-Koyanagi-Harada
      disease unassociated with clinically evident exudative retinal detachment.
AB  - The purpose of this study was to describe the clinical and multimodal imaging
      findings in acute Vogt-Koyanagi-Harada (VKH) disease without clinically evident
      exudative retinal detachment (ERD). We retrospectively reviewed the charts of 18
      patients (36 eyes), diagnosed with acute VKH disease without clinically evident
      ERD. All patients underwent complete ophthalmic examination, fundus photography,
      optical coherence tomography (OCT), B-scan ultrasonography, fluorescein
      angiography (FA), and indocyanine green angiography (ICGA). Of 18 patients,
      twelve (66.7 %) were female and 6 (33.3 %) were male. Mean age was 39 years
      (range, 23-60). Ten patients had been referred with an erroneous diagnosis of
      primary optic nerve disorder (8; 44.4 %) or isolated anterior uveitis (2; 11.1
      %). Anterior chamber or vitreous inflammatory reaction was noted in 22 eyes (61.1
      %), each. Fundus findings included optic disc swelling in 30 eyes (83.3 %),
      retinal striae in 20 eyes (55.5 %), and yellowish deep lesions in 3 eyes (8.3 %).
      OCT showed a shallow, localized subclinical ERD in 18 eyes (50 %), and retinal
      pigment epithelial folds in 23 eyes (63.9 %). B-scan ultrasonography showed
      diffuse, low- to medium-reflective choroidal thickening in all eyes. FA disclosed
      delayed choroidal perfusion in at least one eye of all patients (100 %), mild
      pinpoint leakage in 21 eyes (58.3 %), optic disc hyperfluorescence in 35 eyes
      (97.2 %) and choroidal folds in 13 eyes (36.1 %). ICGA findings included delayed
      choroidal perfusion in 24 eyes (66.7 %), decrease in the number of large
      choroidal vessels in 36 eyes (100 %), fuzzy choroidal vessels in 35 eyes (97.2
      %), and hypofluorescent dark dots in 28 eyes (77.8 %). The association of
      bilateral optic disc edema with retinal striae and intraocular inflammatory
      reaction highly suggests acute VKH disease. A multimodal imaging approach
      including fundus photography, OCT, B-scan ultrasonography, FA, and ICGA provides
      important clues for the definite diagnosis and help differentiate VKH disease
      from primary optic nerve disorders.

PMID- 25939988
TI  - Visual function affects prosocial behaviors in older adults.
AB  - Eye-related pathological conditions such as glaucoma, diabetic retinopathy, and
      age-related macular degeneration commonly lead to decreased peripheral/central
      field, decreased visual acuity, and increased functional disability. We sought to
      answer if relationships exist between measures of visual function and reported
      prosocial behaviors in an older adult population with eye-related diagnoses. The
      sample consisted of adults, aged >= 60 years old, at an academic hospital's eye
      institute. Vision ranged from normal to severe impairment. Medical charts
      determined the visual acuities, ocular disease, duration of disease (DD), and
      visual fields (VF). Measures of giving help were via validated questionnaires on
      giving formal support (GFS) and giving informal support; measures of help
      received were perceived support (PS) and informal support received (ISR). ISR had
      subscales: tangible support (ISR-T), emotional support (ISR-E), and composite
      (ISR-C). Visual acuities of the better and worse seeing eyes were converted to
      LogMAR values. VF information converted to a 4-point rating scale of binocular
      field loss severity. DD was in years. Among 96 participants (mean age 73.28;
      range 60-94), stepwise regression indicated a relationship of visual variables to
      GFS (p < 0.05; Multiple R (2) = 0.1679 with acuity-better eye, VF rating, and
      DD), PS (p < 0.05; Multiple R (2) = 0.2254 with acuity-better eye), ISR-C (p <
      0.05; Multiple R (2) = 0.041 with acuity-better eye), and ISR-T (p < 0.05;
      Multiple R (2) = 0.1421 with acuity-better eye). The findings suggest eye-related
      conditions can impact levels and perceptions of support exchanges. Our data
      reinforces the importance of visual function as an influence on prosocial
      behavior in older adults.

PMID- 25939989
TI  - [The Wearable Cardioverter-Defibrillator (WCD)].
AB  - While the implantable cardioverter-defibrillator (ICD) has been proven to be the
      best choice for patients with long-term risk for sudden cardiac arrest/sudden
      cardiac death (SCA/SCD), the question is how to manage patients with only
      temporary risk, e.g., during the guidelines-recommended waiting period until the
      decision for an ICD can be made. These patient groups should be monitored around
      the clock to guarantee a lifesaving shock within a few minutes, if
      necessary.These conditions can be accomplished by the wearable cardioverter
      defibrillator (WCD) in the outpatient sector. The WCD is worn on the skin and
      consists of four nonadhesive ECG electrodes as well as three defibrillation
      electrodes-two at the back and one at the front-embedded in a garment. The
      defibrillation unit is connected via a cord and can be worn over the shoulder or
      on a belt. Cardiac events can be recorded and retrospectively analyzed by the
      treating physician.The WCD is a safe and effective measure to terminate
      potentially lethal ventricular tachycardia and ventricular fibrillation. It may
      be used early after myocardial infarction with reduced left ventricular ejection
      fraction (LVEF), as well as for patients with acute heart failure in nonischemic
      cardiomyopathy with uncertain cause and prognosis. In addition, it may be used
      for patients waiting for heart transplantation, for patients who cannot be
      implanted an ICD due to comorbidities, and for patients after explantation of
      their ICD, e.g., because of infection until reimplantation.One may expect that
      risk stratification of patients with the WCD will lead to even better selection
      for ICD use.

PMID- 25939990
TI  - High-Performance Planar Perovskite Optoelectronic Devices: A Morphological and
      Interfacial Control by Polar Solvent Treatment.
AB  - Highly efficient planar perovskite optoelectronic devices are realized by amine
      based solvent treatment on compact TiO2 and by optimizing the morphology of the
      perovskite layers. Amine-based solvent treatment between the TiO2 and the
      perovskite layers enhances electron injection and extraction and reduces the
      recombination of photogenerated charges at the interface. 

PMID- 25939991
TI  - Non-enzymatic glucose sensing by enhanced Raman spectroscopy on flexible 'as
      grown' CVD graphene.
AB  - Unmodified, as-grown few layered graphene on copper substrates have been used for
      glucose sensing using Raman spectroscopy. Graphene with a stronger 2D band is a
      better Raman enhancer with significant fluorescence suppression and finer line
      widths of the Raman signals. The origin of the graphene enhanced Raman
      spectroscopy (GERS) signal of glucose is attributed to a fractional charge
      transfer (calculated to be 0.006 using electrochemical parameters) between
      glucose and graphene aided by a possible pi-pi interaction. Physiological
      concentrations of glucose (10-500 mg dl(-1)) in PBS have been used for the study.
      For each glucose concentration, the spectral reproducibility is within 5-25% as
      calculated by the relative standard deviation of several measurements. The
      intensity ratio of the 1122 cm(-1) peak of glucose and the 2D peak of graphene
      varied linearly with the glucose concentration and can be used as a calibration
      curve for unknown sample measurements. 

PMID- 25939992
TI  - Attention-deficit/hyperactivity symptoms in preschool children from an e-waste
      recycling town: assessment by the parent report derived from DSM-IV.
AB  - BACKGROUND: To investigate the attention-deficit/hyperactivity disorder (ADHD)
      status among preschool-aged children in Guiyu, an electronic waste (e-waste)
      recycling town in Guangdong, China. METHODS: Two hundred and forty-three parents
      were surveyed regarding ADHD behaviors in their children (aged 3-7 years) based
      solely on the DSM-IV criteria. The peripheral blood samples were taken from these
      children to measure blood lead levels (BLLs) and blood cadmium levels (BCLs).
      RESULTS: 12.8% of children met the criteria for ADHD, of which the inattentive,
      hyperactive/impulsive and combined subtypes were 4.5%, 5.3% and 2.9%
      respectively. Of all children, 28.0% had BLLs >= 10 ug/dL and only 1.2% had BCLs
      >= 2 ug/L, levels conventionally considered high. Either modeled by univariate or
      multivariable analysis, the three ADHD scores (inattentive, hyperactive/impulsive
      and total scores) calculated from the Parent Rating Scale showed strong positive
      correlations with BLLs but not with BCLs. Furthermore, children with high BLLs
      had 2.4 times higher risk of ADHD than those with low BLLs (OR: 2.4 [95% CI: 1.1
      5.2]). When each of the 18 categories on the Parent Rating Scale was separately
      analyzed, children with high BLLs had significant higher risks for positive ADHD
      symptoms than those with low BLLs in 12 of the 18 categories (ORs ranged from 2.1
      [95% CI: 1.1-3.9] to 3.6 [95% CI: 1.7-7.5]). CONCLUSIONS: This study suggests
      that environmental lead contamination due to e-waste recycling has an impact on
      neurobehavioral development of preschool children in Guiyu.

PMID- 25939993
TI  - Impact of common functional polymorphisms in renin angiotensin system genes on
      the risk of renal parenchymal scarring following childhood urinary tract
      infection.
AB  - BACKGROUND: Pathogenesis of renal parenchymal scarring (RPS) after acute
      pyelonephritis (APN) is unclear. The risk of RPS varies markedly among
      individuals, suggesting a genetic role. OBJECTIVE: To investigate a possible role
      of common polymorphisms in renin angiotensin system genes in APN-associated RPS
      in children. PATIENTS AND METHODS: This study included 104 APN children and 300
      controls. APN was diagnosed by urine culture and typical findings on 99Tc-DMSA
      scans. Voiding cystourethrogram tested the presence of vesicoureteral reflux
      (VUR). Follow-up DMSA scans were performed 4-6 months later to identify new RPS.
      Angiotensin converting enzyme gene I/D, angiotensin II receptor type-1 A1166C and
      angiotensinogen M235T polymorphisms were genotyped. RESULTS: New RPS developed in
      44.2% (46/104) of children with APN. VUR was diagnosed in 35.6% (37/104) of APN
      cases. RPS developed in 73% of cases of VUR. The D allele of ACE gene I/D
      polymorphism was significantly more common in APN cases with RPS (73.91%) than
      non-RPS (58.6%) and controls (54.5%) (p = 0.021, p = 0.002, respectively). The
      AGTR-1 A1166C A allele was significantly more common in VUR than the non-reflux
      children (91.9% versus 76.1%; p = 0.005). VUR, in contrast to the D allele (OR
      6.1, 95% CI 0.878-19.7; p = 0.05), was an independent risk factor for RPS.
      DISCUSSION: ACE gene D allele is associated with a twofold increase in RPS risk,
      which could be a result of a functional effect to increase tissue levels and
      activity of ACE during APN. However, D allele failed to qualify as an independent
      risk and its RPS association could be dependent on other co-factors, such as
      TGFbeta1 activation, or the D-allele might link with recently discovered
      functional polymorphisms at the 5' end of the ACE gene. Although VUR is an
      independent risk for RPS, it is not clear whether this is due to exposure of the
      kidneys to infected urine, or VUR-associated dysplasia. In contrast with
      published literature, we noted higher rates of RPS and high-grade VUR, suggesting
      a more aggressive VUR course or local unawareness of APN. Our study has its
      limitations; the small number of VUR children, and the clinical and ethical
      difficulties of testing VCUG and DMSA in controls. CONCLUSIONS: ACE gene D allele
      is associated with, but cannot independently predict, RPS in children. VUR is an
      independent risk for post-pyelonephritic scarring. AGTR-1 1166A/C polymorphism is
      associated with occurrence, but not progression, of VUR.

PMID- 25939994
TI  - Examination strategies of experienced and novice clinicians viewing the retina.
AB  - PURPOSE: Expertise in viewing medical images is thought to be due to the ability
      to process holistic image information. Eye care clinicians can inspect
      photographs of the retina to search for signs of disease. However, they commonly
      also view the eye in vivo using the restricted view of a slit lamp, which removes
      the potential benefits of holistic processing. We investigated how expert and
      novice clinicians inspect the fundus using these two methods. METHODS: Twenty
      clinicians (10 experienced, 10 novices) examined 64 photographs of human retinae.
      Each participant viewed half of the images as fundus photographs while having
      their eye position recorded. The other half were viewed via a simple slit lamp
      simulation, whereby a computer mouse was used to control the position of a
      viewing window that revealed the underlying fundus photograph. RESULTS:
      Experienced clinicians made decisions significantly faster than novices, with
      faster decision-making when viewing the fundus photograph compared to via the
      slit lamp simulation. The distribution of inspection was similar, although
      novices spent longer examining the optic nerve head than other regions.
      Experienced clinicians showed significantly earlier inspection of the optic nerve
      head when it was judged to be unhealthy. CONCLUSIONS: Our results support the
      idea that experienced eyecare clinicians use holistic image information, if
      available, when inspecting the fundus. This was particularly prominent for the
      optic nerve head region, which was the region that novices spent most of their
      time examining. Holistic processing benefits were only present in experts' free
      viewing fundus photographs; the limited field of view from the slit lamp disrupts
      such global image benefits.

PMID- 25939995
TI  - Magnesium-containing layered double hydroxides as orthopaedic implant coating
      materials--An in vitro and in vivo study.
AB  - The total hip arthroplasty is one of the most common artificial joint replacement
      procedures. Several different surface coatings have been shown to improve implant
      fixation by facilitating bone ingrowth and consequently enhancing the longevity
      of uncemented orthopaedic hip prostheses. In the present study, two different
      layered double hydroxides (LDHs), Mg-Fe- and Mg-Al-LDH, were investigated as
      potential magnesium (Mg)-containing coating materials for orthopaedic
      applications in comparison to Mg hydroxide (Mg(OH)2). In vitro direct cell
      compatibility tests were carried out using the murine fibroblast cell line NIH
      3T3 and the mouse osteosarcoma cell line MG 63. The host response of bone tissue
      was evaluated in in vivo experiments with nine rabbits. Two cylindrical pellets
      (3 * 3 mm) were implanted into each femoral condyle of the left hind leg. The
      samples were analyzed histologically and with MU-computed tomography (MU-CT) 6
      weeks after surgery. An in vitro cytotoxicity test determined that more cells
      grew on the LDH pellets than on the Mg(OH)2-pellets. The pH value and the Mg(2+)
      content of the cell culture media were increased after incubation of the cells on
      the degradable samples. The in vivo tests demonstrated the formation of fibrous
      capsules around Mg(OH)2 and Mg-Fe-LDH. In contrast, the host response of the Mg
      Al-LDH samples indicated that this Mg-containing biomaterial is a potential
      candidate for implant coating.

PMID- 25939996
TI  - PET scan findings can be false positive.

PMID- 25939997
TI  - Defecographic functional evaluation of rectal akinesia.

PMID- 25939998
TI  - Reliable Quantitative SERS Analysis Facilitated by Core-Shell Nanoparticles with
      Embedded Internal Standards.
AB  - Quantitative analysis is a great challenge in surface-enhanced Raman scattering
      (SERS). Core-molecule-shell nanoparticles with two components in the molecular
      layer, a framework molecule to form the shell, and a probe molecule as a Raman
      internal standard, were rationally designed for quantitative SERS analysis. The
      signal of the embedded Raman probe provides effective feedback to correct the
      fluctuation of samples and measuring conditions. Meanwhile, target molecules with
      different affinities can be adsorbed onto the shell. The quantitative analysis of
      target molecules over a large concentration range has been demonstrated with a
      linear response of the relative SERS intensity versus the surface coverage, which
      has not been achieved by conventional SERS methods. 

PMID- 25939999
TI  - Lenticulostriate vasculopathy in neonates: Is it a marker of cerebral insult?
      Critical review of the literature.
AB  - Although lenticulostriate vasculopathy (LSV) was recognized nearly 30 years ago,
      neonatologists and radiologists still question its clinical significance. The
      diagnosis of LSV may be highly subjective, resulting in many false negatives when
      the radiologist is not familiar with the lesion or false positive if over-read by
      those with special interest in this finding. There has been an increase in
      incidence of LSV since its recognition in 1985 which might reflect nothing more
      than a growing awareness of this finding on neonatal cranial ultrasound. On the
      other hand, improved ultrasound imaging technology may have enhanced
      identification of LSV. Prospective studies evaluating the presence, significance
      and diagnosis of LSV are limited and have produced conflicting results.
      Therefore, the associated risk factors and clinical relevance of LSV on cranial
      ultrasound remain unclear. This review will examine the existing literature.

PMID- 25940000
TI  - Lenticulostriate vasculopathy in neonates: Perspective of the radiologist.
AB  - Lenticulostriate vasculopathy (LSV) is a diagnosis dependent on neonatal cranial
      ultrasound (US). The diagnosis of LSV requires the presence of linear or
      branching echogenicities in the area of the basal ganglia and/or thalamus on gray
      scale cranial US. Although the diagnosis of LSV is dependent on cranial US, there
      are no convincing correlates observed on either computerized tomography or
      magnetic resonance imaging. Moreover, the radiographic criteria for LSV on
      cranial US remain vague, and intra-observer correlations are generally reported
      to be poor. The purpose of this review is to examine the issues associated with
      the use of cranial US and the diagnosis of LSV, including alternative imaging,
      clinical abnormalities and the significance of LSV on cranial US. 

PMID- 25940001
TI  - Assessment of Emergency Preparedness of Households in Israel for War--Current
      Status.
AB  - OBJECTIVE: In recent decades, many efforts have been made, both globally and
      locally, to enhance household preparedness for emergencies. In the State of
      Israel in particular, substantial investment has been made throughout the years
      in preparing the population for one of the major threats to the civilian
      population--a rapidly deteriorating regional conflict that involves high
      trajectory weapons (ie, rocket and missile fire) launched at the home front. The
      purpose of this study was to examine the current preparedness level of the
      Israeli public for this threat and determine the correlates of such preparedness
      with known factors. METHODS: A telephone-based, random sampling of 503 households
      representative of the Israeli population was carried out during October 2013. The
      questionnaire examined the level of household preparedness as well as attitudes
      towards threat perception, responsibility, willingness to search for information,
      and sense of preparedness. Statistical analysis was performed to determine the
      level of preparedness in the general population and to find correlates to this
      preparedness in attitudes and demographic variables. RESULTS: More than half of
      the sample reported complying with 50% or fewer of the actions recommended by the
      Israeli Home Front Command. Having an increased sense of preparedness and
      willingness to search for related information were positively correlated with
      actual household preparedness, and the latter was also found to be the most
      predictive variable of household preparedness. CONCLUSIONS: Although the overall
      household preparedness reported is mediocre, the level of preparedness found in
      this study suggests better preparedness of the population in Israel for its
      primary threat. The findings suggest that in order to promote preparedness of the
      Israeli public for war, emphasis should be put on increasing the public demand
      for information and encouraging people to evaluate their sense of preparedness.

PMID- 25940002
TI  - Paternal alcohol exposure in mice alters brain NGF and BDNF and increases ethanol
      elicited preference in male offspring.
AB  - Ethanol (EtOH) exposure during pregnancy induces cognitive and physiological
      deficits in the offspring. However, the role of paternal alcohol exposure (PAE)
      on offspring EtOH sensitivity and neurotrophins has not received much attention.
      The present study examined whether PAE may disrupt nerve growth factor (NGF)
      and/or brain-derived neurotrophic factor (BDNF) and affect EtOH
      preference/rewarding properties in the male offspring. CD1 sire mice were
      chronically addicted for EtOH or administered with sucrose. Their male offsprings
      when adult were assessed for EtOH preference by a conditioned place preference
      paradigm. NGF and BDNF, their receptors (p75(NTR) , TrkA and TrkB), dopamine
      active transporter (DAT), dopamine receptors D1 and D2, pro-NGF and pro-BDNF were
      also evaluated in brain areas. PAE affected NGF levels in frontal cortex,
      striatum, olfactory lobes, hippocampus and hypothalamus. BDNF alterations in
      frontal cortex, striatum and olfactory lobes were found. PAE induced a higher
      susceptibility to the EtOH rewarding effects mostly evident at the lower
      concentration (0.5 g/kg) that was ineffective in non-PAE offsprings. Moreover,
      higher ethanol concentrations (1.5 g/kg) produced an aversive response in PAE
      animals and a significant preference in non-PAE offspring. PAE affected also TrkA
      in the hippocampus and p75(NTR) in the frontal cortex. DAT was affected in the
      olfactory lobes in PAE animals treated with 0.5 g/kg of ethanol while no
      differences were found on D1/D2 receptors and for pro-NGF or pro-BDNF. In
      conclusion, this study shows that: PAE affects NGF and BDNF expression in the
      mouse brain; PAE may induce ethanol intake preference in the male offspring.

PMID- 25940003
TI  - Nature and extent of external-cause deaths of nursing home residents in Victoria,
      Australia.
AB  - OBJECTIVES: To describe the nature and extent of external-cause deaths of
      residents of nursing homes in Victoria, Australia. DESIGN: A retrospective cohort
      study of all decedents using routinely collected data contained within the
      National Coronial Information System. SETTING: Accredited nursing homes in
      Victoria. PARTICIPANTS: Nursing home residents who had died from external causes
      and whose deaths were reported to the Coroners Court between July 1, 2000, and
      December 31, 2012. MEASUREMENTS: Basic descriptive analysis was conducted to
      measure frequencies and proportion of exposures within each outcome group, and
      rates were calculated using population data. RESULTS: One thousand two hundred
      ninety-six external cause deaths of nursing home residents were identified.
      Deaths were due to falls (n=1,155, 89.1%), choking (n=89, 6.9%), suicide (n=17,
      1.3%), complications of clinical care (n=8, 0.6%) and resident-on-resident
      assault (n=7, 0.5%). Deaths occurred more frequently in women (n=814, 62.8%), in
      keeping with the sex distribution in nursing homes, and residents aged 85 and
      older (n=923, 71.2%). The number of inquests held to investigate a death as a
      matter of public interest was small (n=24, 1.9%). CONCLUSION: A significant
      proportion of nursing home resident deaths are from external causes and are
      potentially preventable. A shift in community attitudes is required toward an
      understanding that premature death of a resident from injury is not a natural
      part of life.

PMID- 25940004
TI  - The motor function of Drosophila melanogaster myosin-5 is activated by calcium
      and cargo-binding protein dRab11.
AB  - In the Drosophila melanogaster compound eye, myosin-5 (DmM5) plays two distinct
      roles in response to light stimulation: transport of pigment granules to the
      rhabdomere base to decrease light exposure and transport of rhodopsin-bearing
      vesicles to the rhabdomere base to compensate for the rhodopsin loss during light
      exposure. However, little is known of how the motor function of DmM5 is regulated
      at the molecular level. In the present study, we overexpressed DmM5 in Sf9 insect
      cells and investigated its regulation using purified proteins. We found that the
      actin-activated ATPase activity of DmM5 is significantly lower than that of the
      truncated DmM5 having the C-terminal globular tail domain (GTD) deleted,
      indicating that the GTD is the inhibitory domain. The actin-activated ATPase
      activity of DmM5 is significantly activated by micromolar levels of calcium. DmM5
      associates with pigment granules and rhodopsin-bearing vesicles through cargo
      binding proteins Lightoid (Ltd) and dRab11 respectively. We found that GTP-bound
      dRab11, but not Ltd, significantly activates DmM5 actin-activated ATPase
      activity. Moreover, we identified Gln(1689) in the GTD as the critical residue
      for the interaction with dRab11 and activation of DmM5 motor function by dRab11.
      Based on those results, we propose that DmM5-dependent transport of pigment
      granules is directly activated by light-induced calcium influx and the DmM5
      dependent transport of rhodopsin-bearing vesicle is activated by active GTP-bound
      dRab11, whose formation is stimulated by light-induced calcium influx. 

PMID- 25940005
TI  - Familial Risk of Sjogren's Syndrome and Co-aggregation of Autoimmune Diseases in
      Affected Families: A Nationwide Population Study.
AB  - OBJECTIVE: To investigate familial aggregation of Sjogren's syndrome (SS) and the
      relative risks (RRs) of other autoimmune disease in relatives of patients with
      SS. METHODS: We identified 23,658,577 beneficiaries enrolled in the Taiwan
      National Health Insurance system in 2010, of whom 12,754 had SS. We identified
      21,009,551 parent-child relationships and 17,168,340 pairs of full siblings. The
      familial risks of SS and other autoimmune diseases, tetrachoric correlation, and
      familial transmission were estimated. RESULTS: We identified 105 patients with SS
      who had an affected first-degree relative. The RR of SS was 18.99 (95% confidence
      interval [95% CI] 9.76-36.93) in siblings of patients with SS, 11.31 (95% CI 8.34
      15.33) in offspring, and 12.46 (95% CI 9.34-16.62) in parents. Tetrachoric
      correlation coefficients were 0.53 (95% CI 0.41-0.65) for cotwins of affected
      individuals and 0.21 (95% CI 0.16-0.26) for full siblings. The familial
      transmission (heritability plus shared environmental contribution) was 0.54 (95%
      CI 0.44-0.77). In first-degree relatives of patients with SS, the RRs were 2.95
      (95% CI 2.33-3.73) for rheumatoid arthritis, 6.25 (95% CI 5.15-7.58) for systemic
      lupus erythematosus, 2.39 (95% CI 0.77-7.41) for systemic sclerosis, 0.71 (95% CI
      0.10-5.07) for idiopathic inflammatory myopathy, 1.97 (95% CI 1.29-3.02) for type
      1 diabetes mellitus, 3.38 (95% CI 1.26-9.05) for multiple sclerosis, 1.67 (95% CI
      0.83-3.33) for myasthenia gravis, 1.25 (95% CI 1.04-1.50) for psoriasis, 1.21
      (95% CI 0.39-3.76) for inflammatory bowel disease, and 2.29 (95% CI 1.19-4.40)
      for vasculitis. CONCLUSION: The risk of SS and other autoimmune diseases is
      increased in relatives of patients with SS, and more than one-half of phenotypic
      variance in SS can be explained by familial factors.

PMID- 25940006
TI  - Quantitative and functional pulsed arterial spin labeling in the human brain at
      9.4 T.
AB  - PURPOSE: The feasibility of multislice pulsed arterial spin labeling (PASL) of
      the human brain at 9.4 T was investigated. To demonstrate the potential of
      arterial spin labeling (ASL) at this field strength, quantitative, functional,
      and high-resolution (1.05 * 1.05 * 2 mm(3)) ASL experiments were performed.
      METHODS: PASL was implemented using a numerically optimized adiabatic inversion
      pulse and presaturation scheme. Quantitative measurements were performed at 3 T
      and 9.4 T and evaluated on a voxel-by-voxel basis. In a functional experiment,
      activation maps obtained with a conventional blood-oxygen-level-dependent (BOLD)
      weighted sequence were compared with a functional ASL (fASL) measurement.
      RESULTS: Quantitative measurements revealed a 23% lower perfusion in gray matter
      and 17% lower perfusion in white matter at 9.4 T compared with 3 T. Furthermore
      almost identical transit delays and bolus durations were found at both field
      strengths whereas the calculated voxel volume corrected signal-to-noise ratio was
      1.9 times higher at 9.4 T. This result was confirmed by the high-resolution
      experiment. The functional experiment yielded comparable activation maps for the
      fASL and BOLD measurements. CONCLUSION: Although PASL at ultrahigh field
      strengths is limited by high specific absorption rate, functional and
      quantitative perfusion-weighted images showing a high degree of detail can be
      obtained.

PMID- 25940007
TI  - [Individualized, personalized and stratified medicine: a challenge for
      allergology in ENT?].
AB  - Individualized, personalized or stratified medicine approaches offer emerging
      opportunities in the field of allergy and ENT. Avoidance of side effects,
      targeted therapy approaches and stratified prevention promise better outcomes and
      optimal results for patients. Conceptual incongruencies remain with regard to
      definitions and perceptions of "personalized medicine". Serious ethical
      considerations have to be taken into account. The development of
      pharmacogenomics, molecular phenotyping, genomic sequencing and other -omics
      opens the door to unique mechanistic therapeutic advances. The molecular
      allergology and recombinant diagnostics available are tools that offer
      substantial improved diagnostics for the benefit of allergic patients, e. g. in
      anaphylaxis and food allergy. For stratified therapeutic approaches, however,
      regulatory affairs will have to keep pace with medical and scientific discovery.

PMID- 25940008
TI  - [Polypoid lesions of the auditory canal in children].

PMID- 25940009
TI  - [On the underestimation of normal hearing].

PMID- 25940010
TI  - Dairy cattle management factors that influence on-farm density of European
      starlings in Ohio, 2007-2009.
AB  - Potential dairy farm management and environmental factors that attract European
      starlings (Sturnus vulgaris) to dairy farms were explored. During the period from
      2007 to 2009, 150 dairy farms were each visited twice (once during the summer and
      again in the fall) and the number of starlings was recorded. Risk factors were
      assessed for possible association with the number of starlings per milking cow
      (starling density), using a zero-inflated negative binomial model. Starling
      density was higher on farms visited in 2007 compared to those visited in 2008 or
      2009. The interaction term between feeding method and feeding site was
      significantly associated with starling density on farm; generally, feeding
      outdoors was associated with increased starling density. The odds of a zero
      starling count (compared to a count greater than zero) was higher on farms that
      removed manure from barns weekly or less frequently than weekly compared to those
      that removed manure daily or after every milking. The odds of a zero starling
      count decreased with increasing distance of a farm from the closest night roost.
      Identifying on farm risk factors that expose farms to starlings will help farmers
      develop strategies that minimize the number of birds on their farms and thereby
      reduce physical damage to the farms as well as the potential for pathogen
      transmission from birds to cattle and humans. 

PMID- 25940016
TI  - Isolation, characterization, and in vitro evaluation of bovine rumen submucosa
      films of collagen or chitosan-treated collagen.
AB  - Bovine rumen is hitherto considered as an inedible waste of meat industry. The
      rumen tissues can be used as an alternative source of collagen to produce
      biocompatible materials for clinical application. In an effort to develop a
      functional biomaterial from the inedible mammalian tissues, this study aims to
      isolate and characterize bovine rumen submucosa. Initially, the rumen tissue was
      sequentially processed using chemical and enzymatic treatment to decellularize,
      neutralize, stabilize, and to produce a native collagen matrix which is referred
      as collagen film (COL-F). Thus, prepared matrix was treated with 1% (w/v)
      chitosan solution to produce a hybrid film which is referred as collagen-chitosan
      film (COL/CS-F). The comparative study includes the evaluation of physical,
      chemical, and biological properties of the biofilms prepared. The surface
      topology of COL-F exhibited a continuous collagenous network with fibrous nature,
      while the chitosan treatment provided smooth plain surface to the parent film.
      Incorporation of chitosan in COL-F increased the tensile properties, as well as
      the thermal stability and durability of the films. The Fourier Transform Infrared
      spectroscopy results revealed the presence of respective amide peaks, which
      corresponds to protein (collagen), and the evidence of collagen-chitosan
      interlinking. The submucosa layer was electrophoretically found to have type I
      collagen. The X-ray diffraction data showed the presence of amorphous and
      crystalline peak which attributes to the triple helical structure of collagen in
      the films. Cytotoxicity studies on the films were performed in vitro using human
      keratinocytes. The results of cell viability and proliferation demonstrated that
      COL-F and COL/CS-F exhibit good biocompatibility and therefore can augment cell
      infiltration and proliferation. However, enhanced cellular activity was observed
      on the chitosan treated COL-F. These observations demonstrate that the biofilms
      prepared in this study can be used as an alternative functional biomaterial in
      tissue engineering. 

PMID- 25940017
TI  - Methotrexate-loaded glass ionomer cements for drug release in the skeleton: An
      examination of composition-property relationships.
AB  - Chemotherapeutic-loaded bone cement may be an effective method of drug delivery
      for the management of cancer-related vertebral fractures that require cement
      injection for pain relief. Recent advancements in the development of aluminum
      free glass ionomer cements (GICs) have rendered this class of biomaterials
      clinically viable for such applications. To expand the therapeutic benefits of
      these materials, this study examined, for the first time, their drug delivery
      potential. Through incrementally loading the GIC with methotrexate (MTX) by up to
      10-wt%, composition-property relationships were established, correlating MTX
      loading with working time and setting time, as well as compressive strength, drug
      release, and cytotoxic effect over 31 days. The most significant finding of this
      study was that MTX was readily released from the GIC, while maintaining cytotoxic
      activity. Release correlated linearly with initial loading and appeared to be
      diffusion mediated, delivering a total of 1-2% of the incorporated drug. MTX
      loading in this range exerted minimal effects to handling and strength,
      indicating the clinical utility of the material was not compromised by MTX
      loading. The MTX-GIC systems examined herein are promising materials for combined
      structural delivery applications. 

PMID- 25940015
TI  - Effect of l-lysine-assisted surface grafting for nano-hydroxyapatite on
      mechanical properties and in vitro bioactivity of poly(lactic acid-co-glycolic
      acid).
AB  - It is promising and challenging to study surface modification for nano
      hydroxyapatite to improve the dispersion and enhance the mechanical properties
      and bioactivity of poly(lactic acid-co-glycolic acid). In this paper, we designed
      an effective new surface grafting with the assist of l-lysine for nano
      hydroxyapatite, and the nano-hydroxyapatite surface grafted with the assist of l
      lysine (g-nano-hydroxyapatite) was incorporated into poly(lactic acid-co-glycolic
      acid) to develop a series of g-nano-hydroxyapatite/poly(lactic acid-co-glycolic
      acid) nano-composites. The surface modification reaction for nano-hydroxyapatite,
      the mechanical properties, and in vitro human osteoblast-like cell (MG-63)
      response were characterized and investigated by Fourier transformation infrared,
      thermal gravimetric analysis, dispersion test, electromechanical universal
      tester, differential scanning calorimeter measurements, and in vitro cells
      culture experiment. The results showed that the grafting amount on the surface of
      nano-hydroxyapatite was enhanced with the increase of l-lysine, and the
      dispersion of nano-hydroxyapatite was improved more, so that it brought about
      better promotion crystallization and more excellent mechanical enhancement effect
      for poly(lactic acid-co-glycolic acid), comparing with the unmodified nano
      hydroxyapatite. Moreover, the cells' attachment and proliferation results
      confirmed that the incorporation of the g-nano-hydroxyapatite into poly(lactic
      acid-co-glycolic acid) exhibited better biocompatibility than poly(lactic acid-co
      glycolic acid). The above results indicated that the new surface grafting with
      the assist of l-lysine for nano-hydroxyapatite was an ideal novel surface
      modification method, which brought about better mechanical enhancement effect and
      in vitro bioactivity for poly(lactic acid-co-glycolic acid) with adding higher g
      nano-hydroxyapatite content, suggesting it had a great potential to be used as
      bone fracture internal fixation materials in future. 

PMID- 25940018
TI  - Perceived skin colour seems a swift, valid and reliable measurement.

PMID- 25940020
TI  - Cervical squamous cell carcinoma metastatic to pericardial fluid--large cell
      balls masquerade as adenocarcinoma.

PMID- 25940019
TI  - Preventing diarrhoea in enteral nutrition: the impact of the delivery set hang
      time.
AB  - BACKGROUND: To meet the current recommendations for enteral tube feeding (ETF),
      we updated our previous practice in 2011 and began to use a 24-h delivery set
      hang time (DSHT). We evaluated the impact of this update on the risk of diarrhoea
      and in diarrhoea-free survival. METHODS: Observational, retrospective study with
      historical controls on ischaemic and haemorrhagic stroke patients undergoing ETF.
      Diarrhoea occurrence (>= 3 liquid stools in 24 h) was compared between patients
      with a 24 h DSHT (2011-2014) and a 72/96 h DSHT (2010-2011). The analysis was
      conducted using Kaplan-Meier curves and a Cox regression model. RESULTS: A total
      of 175 patients were included [median age 81 years (IQR = 12), 46.9% males], 103
      in the group with a 24 h DSHT and 72 in the group with a 72/96 h DSHT. The group
      with a 24 h DSHT had a lower diarrhoea frequency (13.6% vs. 34.7%, risk ratio:
      0.39, 95% CI: 0.22-0.70, p = 0.001) and a lower diarrhoea incidence rate (0.87
      vs. 2.32 cases of diarrhoea/100 patient*day, rate ratio: 0.37, 95% CI: 0.19-0.72,
      p = 0.004). The Kaplan-Meier curves showed a longer diarrhoea-free survival for
      this group (p = 0.003, log-rank test). A 24 h DSHT was associated with a lower
      risk of diarrhoea (HR = 0.27, 95% CI: 0.12-0.61, p = 0.002), adjusted by albumin,
      stroke severity, intravenous thrombolysis, the administration of clindamycin and
      cefotaxime, and the administration of an enteral formula for diabetic patients.
      CONCLUSIONS: The 24 h DSHT was independently associated with a lower risk of
      diarrhoea and longer diarrhoea-free survival in hospitalised patients with acute
      stroke under ETF, compared with a 72/96 h DSHT.

PMID- 25940021
TI  - Poor sleep and reactive aggression: Results from a national sample of African
      American adults.
AB  - BACKGROUND: We know that poor sleep can have important implications for a variety
      of health outcomes and some evidence suggests a link between sleep and aggressive
      behavior. However, few studies have looked at this relationship among African
      Americans in the United States. METHODS: Data from the National Survey of
      American Life (NSAL) and the NSAL Adult Re-Interview were used to examine
      associations between sleep duration and self-reported quality of sleep on
      reactive aggression among African American and Caribbean Black respondents
      between the ages of 18 and 65 (n = 2499). RESULTS: Controlling for an array of
      sociodemographic and psychiatric factors, sleep was found to be significantly
      associated with reactive aggression. Specifically, individuals who reported
      sleeping on average less than 5 h per night were nearly three times more likely
      to report losing their temper and engaging in a physical fight (AOR = 3.13, 95%
      CI = 1.22-8.02). Moreover, individuals who reported being "very dissatisfied"
      with their sleep were more than two times more likely to report losing their
      temper and engaging in physical fights (AOR = 3.32, 95% CI = 1.50-7.33). Persons
      reporting everyday discrimination and problems managing stress were more likely
      to sleep poorly. CONCLUSIONS: The present study is among the first to document an
      association between poor sleep and reactive violence among African-Americans.
      Findings suggest that reducing discrimination may lead to improved sleep and
      subsequently reduce forms of reactive violence.

PMID- 25940022
TI  - Discovering what works well: exploring quality dementia care in hospital wards
      using an appreciative inquiry approach.
AB  - AIMS AND OBJECTIVES: To explore the quality dementia care in two geriatric
      hospital wards using appreciative inquiry with formal care workers and family
      members of inpatients with dementia. BACKGROUND: Care models such as person
      centred and relationship-centred care have been developed to explain what
      'quality' dementia care should be. However, their usefulness and relevance to
      clinicians has been questioned. DESIGN: Using an exploratory qualitative design
      within an appreciative inquiry framework, 33 care workers working in a geriatric
      hospital and 10 family members of patients with dementia were interviewed.
      METHODS: Open-ended questions were asked to encourage care workers to narrate
      positive care experiences when the care was perceived to be at its best and to
      identify what made these experiences possible. Interviews were audio-taped and
      transcribed whilst data were analysed thematically using a qualitative data
      analysis software to assist in data management. RESULTS: Positive care
      experiences can be understood within five care processes, namely building a
      relationship between the 'extended' dementia care triad, providing 'quality time'
      and 'care in time', going the 'extra mile', attending to the psychosocial needs
      and attending to the physical needs with a 'human touch'. Factors facilitating
      these positive care experiences included personal attributes of care workers, and
      organisational, environmental and contextual factors. CONCLUSIONS: This study
      provides an alternative and pragmatic approach to understanding quality dementia
      care and complements the body of knowledge on factors influencing dementia care
      practices in hospitals. RELEVANCE TO CLINICAL PRACTICE: By understanding the
      components of quality dementia care and how these can be achieved from different
      stakeholders, it is possible to develop strategies aimed at improving the care
      offered to patients with dementia in hospitals.

PMID- 25940023
TI  - An Amorphous Carbon Nitride Composite Derived from ZIF-8 as Anode Material for
      Sodium-Ion Batteries.
AB  - An composite comprising amorphous carbon nitride (ACN) and zinc oxide is derived
      from ZIF-8 by pyrolysis. The composite is a promising anode material for sodium
      ion batteries. The nitrogen content of the ACN composite is as high as 20.4 %,
      and the bonding state of nitrogen is mostly pyridinic, as determined by X-ray
      photoelectron spectroscopy (XPS). The composite exhibits an excellent Na(+)
      storage performance with a reversible capacity of 430 mA h g(-1) and 146 mA h g(
      1) at current densities of 83 mA g(-1) and 8.33 A g(-1) , respectively. A
      specific capacity of 175 mA h g(-1) was maintained after 2000 cycles at 1.67 A g(
      1) , with only 0.016 % capacity degradation per cycle. Moreover, an accelerating
      rate calorimetry (ARC) test demonstrates the excellent thermal stability of the
      composite, with a low self heating rate and high onset temperature (210  degrees
      C). These results shows its promise as a candidate material for high-capacity,
      high-rate anodes for sodium-ion batteries.

PMID- 25940024
TI  - Efficient wheat germ agglutinin purification with a chitosan-based affinity
      chromatographic matrix.
AB  - An efficient affinity chromatographic matrix based on chitosan for wheat germ
      agglutinin (WGA) purification was developed. The matrices assayed consisted of
      chitosan mini-spheres cross-linked with epichlorhydrin 45, 250 or 500 mM. The
      maximum adsorption capacity of pure WGA - calculated from the corresponding
      isotherms - was between 43.2 and 48.9 mg/g at pH 5.0 and between 16.6 and 27.6
      mg/g at pH 8.5. However, the adsorption of agglutinin from wheat germ extract was
      higher at pH 8.5. In addition, 0.5 g of mini-spheres cross-linked with
      epichlorhydrin 250 mM adsorbed 94.5% of the WGA present in 5 mL of the
      concentrated extract. Acetic acid was able to elute 100% of the adsorbed WGA. The
      purity of the WGA obtained was greater than 95% and the purification factor was
      56.8. The matrix was able to maintain an efficient performance of the
      purification process for three consecutive cycles. A new method to monitor the
      purification process by RP-HPLC was developed. 

PMID- 25940025
TI  - Drug transport and metabolism of novel anticancer drugs.

PMID- 25940026
TI  - Physiologically based pharmacokinetic and pharmacodynamic modeling in cancer drug
      development: status, potential and gaps.
AB  - INTRODUCTION: Modeling and simulation have become important means of answering
      questions relevant to the development of a drug, making it possible to assess
      risks early and to reduce costs. Physiologically based pharmacokinetic and
      pharmacodynamic (PBPK/PD) models contribute to a comprehensive understanding of
      the drug, covering specific questions from early discovery through lifecycle
      management stages. As for other disease areas, in oncology, PBPK and PD models
      are important topics that remain to be addressed. AREAS COVERED: This review
      describes current PBPK and PD approaches, their applicability in drug development
      in general and specifically in the area of oncology. It discusses the current
      status and then focuses on key challenges and the potential for future use. It
      provides cases in which modeling currently cannot answer the questions and
      assesses the requirements to close gaps for PBPK/PD in oncology. EXPERT OPINION:
      PBPK/PD models have led to improvements in identifying risks and reducing costs
      during the drug development process. Nevertheless, there is a lot of potential,
      where more rigorous integration of biological knowledge and specific experimental
      design would result in a more comprehensive biological picture. Ideally, such
      approaches would reveal the extent to which preclinical work can be extrapolated
      to clinical settings, thus enabling reliable prediction and, ultimately, reducing
      failed trials in clinical oncology.

PMID- 25940029
TI  - Severity of aortic regurgitation assessed by area of vena contracta: a clinical
      two-dimensional and three-dimensional color Doppler imaging study.
AB  - BACKGROUND: Quantitation of aortic regurgitation (AR) using two-dimensional (2D)
      echocardiography, including vena contracta width (VCW) measurement, is still
      challenging. Three-dimensional (3D) echocardiography can directly measure the
      vena contracta area (VCA), regardless of the rheological characteristics. We
      intended to assess the possibility of 3D vena contracta area (3DVCA) as well as
      2D vena contracta area (2DVCA) in the assessment of AR severity. METHODS: Sixty
      one patients with AR [17 female (32.7%); mean age: 74.0 +/- 10.1 years] underwent
      2D and 3D color Doppler echocardiography. Using conventional 2D color Doppler
      imaging, we measured VCW, 2DVCA, regurgitant volume (RV), and effective
      regurgitant orifice area (EROA). We also measured 3DVCA manually off-line from 3D
      full-volume color Doppler datasets for reference. Comprehensive 2D and 3D data on
      AR severity were successfully obtained from 52 of the 61 (85.2%) patients.
      RESULTS: Significant correlations existed between 2DVCA and EROA (r = 0.89; p <
      0.001). The cut-off 2DVCA for grading severe AR was 34 mm2 (area under curve:
      0.95; sensitivity: 78%; specificity: 95%). Significant correlations existed
      between 3DVCA and EROA (r = 0.89; p < 0.001). The cut-off 3DVCA for grading
      severe AR was 32 mm2 (area under curve: 0.96; sensitivity: 89%; specificity:
      98%). Significant correlations existed between 2DVCA and 3DVCA (r = 0.97; p <
      0.001). CONCLUSION: Two-dimensional, as well as three dimensional, vena contracta
      area measurement is a simple technique suitable for clinical use during
      comprehensive Doppler echocardiographic AR assessment.

PMID- 25940027
TI  - Effect of age on drug metabolism in women with breast cancer.
AB  - INTRODUCTION: The aging of the population will increase the number of breast
      cancer patients requiring treatment in both the adjuvant and metastatic setting.
      Hormones, chemotherapy and targeted drugs all have a role in treatment. Older
      patients have been underrepresented in clinical trials making evidence-based
      decisions difficult. The increase in comorbidity and aging, polypharmacy and
      changes in function make pharmacotherapy decisions more complicated. Knowledge of
      the issues is critical in the prescribing of effective and safe therapy. There
      are factors associated with advancing age that can result in pharmacokinetic and
      pharmacodynamic variations in processing of hormonal agents, chemotherapy and
      targeted drugs. AREAS COVERED: A review of the literature pertaining to
      pharmacokinetic changes in aging in breast cancer was untaken. Studies are
      reviewed involving single agents and some combinations. EXPERT OPINION: Older
      patients should be considered for standard therapies. Their specific problems
      need to be evaluated by geriatric-specific assessment including functional
      status, end organ dysfunction and polypharmacy. There are few instances for age
      related changes in pharmacokinetics and when present are usually not clinically
      significant. When changes are present, they are often the result of comorbidity,
      drug interactions and drug scheduling issues. The older patients may be more
      sensitive to certain toxicities such as cardiac toxicity, neuropathy and
      myelosuppression.

PMID- 25940030
TI  - Study of rolapitant, a novel, long-acting, NK-1 receptor antagonist, for the
      prevention of chemotherapy-induced nausea and vomiting (CINV) due to highly
      emetogenic chemotherapy (HEC).
AB  - PURPOSE: Rolapitant is a novel, long-acting neurokinin-1 (NK-1) receptor
      antagonist. This study evaluated the safety and efficacy of four different doses
      of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV)
      due to highly emetogenic chemotherapy (HEC). METHODS: This randomized, double
      blind, active-controlled, global study was conducted in patients receiving
      cisplatin-based chemotherapy >=70 mg/m(2). Patients received a 9, 22.5, 90, or
      180 mg oral dose of rolapitant or placebo with ondansetron and dexamethasone on
      day 1 of chemotherapy. The primary end point was complete response (CR; no emesis
      and no use of rescue medication) in the overall (0 to 120 h) phase of cycle 1.
      Other assessments were CR in delayed (24-120 h) and acute (0-24 h) phases, no
      emesis, no significant nausea, and no nausea. RESULTS: Four hundred fifty-four
      patients were randomized. All doses of rolapitant improved CR with the greatest
      benefit observed with rolapitant 180 mg vs. active control in the overall phase
      (62.5 and 46.7 %, p = 0.032) and in the acute (87.6 vs. 66.7 %, p = 0.001) and
      delayed (63.6 vs. 48.9 %, p = 0.045) phases. Rates for no emesis and no
      significant nausea were significantly (p < 0.05) higher with rolapitant 180 mg
      vs. active control in the overall, acute, and delayed phases. Treatment-related
      adverse events were largely considered related to the chemotherapy and included
      constipation, headache, fatigue, and dizziness which were mostly mild or moderate
      and were similar across treatment groups. CONCLUSION: All doses of rolapitant
      were well tolerated and showed greater CR rates than active control. Rolapitant
      180 mg demonstrated significant clinical efficacy for preventing CINV in the
      overall, delayed, and acute phases for patients receiving HEC.

PMID- 25940031
TI  - Financial burden of therapy in families with a child with acute lymphoblastic
      leukemia: report from north India.
AB  - BACKGROUND: In a low-income country, a child with cancer has severe financial
      implications for the family. Invariably, patients have to self-finance their
      therapy. "Out-of-pocket" expenses tend to be high. Also, parents may face loss of
      job or business resulting in loss of income. Our objective was to assess the
      financial burden in families with a child with cancer. PROCEDURE: The cost to a
      family with a child with acute lymphoblastic leukemia (ALL) during the first
      month of therapy was analyzed. Fifty families were given a cost diary in which
      details of expenditure (direct medical costs, living costs, transport cost) and
      lost income/employment were recorded. RESULTS: The families evaluated came from a
      distance of 260 +/- 218 km from hospital. Most families belonged to upper lower
      category (62%). The medical expenditure amounted to US dollar (USD) 524
      (interquartile range (IQR) 395-777). Nonmedical expenditure was USD 207 (IQR 142
      293), the maximum expenditure being on food. The monthly expenses were 7.2 times
      the monthly per capita income of India which was Indian rupee (INR) 5729 (USD 97)
      in 2012-2013. Thirty-nine families got financial help (USD 800-3225) from various
      sources, within 6 months of application. Of the families, 72% families suffered
      loss of income, 34% fathers lost their jobs. CONCLUSIONS: Families spend up to
      seven times their monthly income over a period of 1 month on an unforeseen
      illness. Despite financial aid from various sources, nonmedical costs amount to
      nearly 2.5 times the average per capita income. Universal health insurance is the
      need of the hour.

PMID- 25940032
TI  - Angiomyolipoma being surgically excised for presumed kidney carcinoma.
AB  - OBJECTIVE: To explore the important factors involved in angiomyolipoma (AML)
      being preoperatively misclassified and surgically removed for presumed kidney
      carcinoma. MATERIALS AND METHODS: From 2008 to 2014, AML was pathologically
      confirmed in 38 patients who underwent radical or partial nephrectomy for
      presumed malignant renal tumor. Control group 1 were patients with renal cell
      carcinoma (RCC) matched for age and tumor size; control group 2 were patients
      with typical AML matched for age and sex. Pertinent data of the studied group and
      its matched control groups were recorded and analyzed. RESULTS: The mean age of
      the patients in study group was 48.11 +/- 12.92 years, and the mean tumor size
      was 3.12 +/- 1.68 cm (range 0.9-9.4). More than 84 % of the misclassified AMLs
      measured <=4 cm, and over 21 % patients underwent radical nephrectomy. The only
      statistically significant feature between the misdiagnosed AML group and the
      matched RCC group is mean age (48.11 +/- 12.92 vs. 56.92 +/- 10.28, P = 0.002).
      Compared with the matched typical AML group, the misdiagnosed AML group has
      smaller mean tumor size (3.12 +/- 1.68 vs. 5.85 +/- 3.33, P < 0.001), but more
      patients undergoing radical nephrectomy (21.05 vs. 0 %, P = 0.003). Two main
      imaging features, which are hypoechoic on ultrasonography and fat density on
      computed tomography (CT), were statistically different between the two groups.
      The misdiagnosis of AML was significantly associated with no fat density on CT
      (OR 5.528, P = 0.004) and hypoechoic on ultrasonography (OR 3.845, P = 0.017).
      CONCLUSIONS: A number of AMLs were misdiagnosed as RCCs, causing a large number
      of unnecessary surgeries. No fat density on CT and no hyperechoic on
      ultrasonography resulting from small tumor size were the two most important
      factors causing AML being excised for presumed kidney carcinoma. Ultrasonography
      and CT cannot differentiate atypical AML from kidney carcinoma effectively, so
      improved renal biopsy and noninvasive biomarkers are urgently warranted to
      prevent us from excising benign renal tumor aggressively.

PMID- 25940033
TI  - Ischemic postconditioning inhibits apoptosis of renal cells following
      reperfusion: a novel in vitro model.
AB  - PURPOSE: The majority of renal ischemic/reperfusion (I/R) and ischemic
      postconditioning (IPO) studies have been based on animal models. To gain
      mechanistic insights into ischemic postconditioning-induced alterations at the
      cell level, a novel in vitro model of I/R and IPO is set up by using the rat
      proximal tubule cell line NRK-52E. METHODS: Cells are incubated in 1 mL ischemic
      buffer under hypoxia conditions for 3 h to simulate the clinical condition of a
      cellular microenvironment representative of ischemia, including oxygen
      deprivation, carbon dioxide elevation, nutrient depletion, and waste
      accumulation. IPO model is established by exposing the cells to three cycles of
      'mimic reperfusion condition' for 10 min and ischemic condition for 10 min after
      placing the cells in ischemic condition for 3 h. Flow cytometry and Hoechst are
      used to assessing apoptosis. The expression spot and protein levels of PDK, Akt,
      and ERK are also analyzed. RESULTS: I/R results in severe injury in NRK-52E cells
      as evidenced by increased LDH leakage in the culture medium, as well as increased
      apoptotic index, which may be significantly attenuated by IPO treatment applied
      before the abrupt reperfusion (P < 0.05 vs. I/R group). Meanwhile, IPO, compared
      with I/R, increases phosphorylation levels of Akt and ERK (P < 0.05 vs. I/R
      group), which have been identified to play a vital role in the regulation of cell
      proliferation, survival, and metabolism. CONCLUSION: A new in vitro model of I/R
      and IPO is established successfully. These results offer evidence that 3 h of
      simulating ischemic/reperfusion injury may cause cell apoptosis, and IPO is
      effective to attenuate renal cell apoptosis and potentially mediate via
      activation of Akt and ERK signal.

PMID- 25940034
TI  - Nitisinone Arrests but Does Not Reverse Ochronosis in Alkaptonuric Mice.
AB  - Alkaptonuria (AKU) is an ultrarare autosomal recessive disorder resulting from a
      deficiency of homogentisate 1,2 dioxygenase (HGD), an enzyme involved in the
      catabolism of phenylalanine and tyrosine. Loss of HGD function prevents
      metabolism of homogentisic acid (HGA), leading to increased levels of plasma HGA
      and urinary excretion. Excess HGA becomes deposited in collagenous tissues and
      subsequently undergoes polymerisation, principally in the cartilages of loaded
      joints, in a process known as ochronosis. This results in an early-onset,
      devastating osteoarthropathy for which there is currently no effective treatment.
      We recently described the natural history of ochronosis in a murine model of AKU,
      demonstrating that deposition of ochronotic pigment begins very early in life and
      accumulates with age. Using this model, we were able to show that lifetime
      treatment with nitisinone, a potential therapy for AKU, was able to completely
      prevent deposition of ochronotic pigment. However, although nitisinone has been
      shown to inhibit ochronotic deposition, whether it can also facilitate removal of
      existing pigment has not yet been examined. We describe here that midlife
      administration of nitisinone to AKU mice arrests further deposition of ochronotic
      pigment in the tibiofemoral joint, but does not result in the clearance of
      existing pigment. We also demonstrate the dose-dependent response of plasma HGA
      to nitisinone, highlighting its efficacy for personalised medicine, where dosage
      can be tailored to the individual AKU patient. 

PMID- 25940035
TI  - Mitochondrial DNA Depletion and Deletions in Paediatric Patients with
      Neuromuscular Diseases: Novel Phenotypes.
AB  - OBJECTIVE: To study the clinical manifestations and occurrence of mtDNA depletion
      and deletions in paediatric patients with neuromuscular diseases and to identify
      novel clinical phenotypes associated with mtDNA depletion or deletions. METHODS:
      Muscle DNA samples from patients presenting with undefined encephalomyopathies or
      myopathies were analysed for mtDNA content by quantitative real-time PCR and for
      deletions by long-range PCR. Direct sequencing of mtDNA maintenance genes and
      whole-exome sequencing were used to study the genetic aetiologies of the
      diseases. Clinical and laboratory findings were collected. RESULTS: Muscle
      samples were obtained from 104 paediatric patients with neuromuscular diseases.
      mtDNA depletion was found in three patients with severe early-onset
      encephalomyopathy or myopathy. Two of these patients presented with novel types
      of mitochondrial DNA depletion syndromes associated with increased serum creatine
      kinase (CK) and multiorgan disease without mutations in any of the known mtDNA
      maintenance genes; one patient had pathologic endoplasmic reticulum (ER)
      membranes in muscle. The third patient with mtDNA depletion was diagnosed with
      merosine-deficient muscular dystrophy caused by a homozygous mutation in the
      LAMA2 gene. Two patients with an early-onset Kearns-Sayre/Pearson-like phenotype
      harboured a large-scale mtDNA deletion, minor multiple deletions and high mtDNA
      content. CONCLUSIONS: Novel encephalomyopathic mtDNA depletion syndrome with
      structural alterations in muscle ER was identified. mtDNA depletion may also
      refer to secondary mitochondrial changes related to muscular dystrophy. We
      suggest that a large-scale mtDNA deletion, minor multiple deletions and high
      mtDNA content associated with Kearns-Sayre/Pearson syndromes may be secondary
      changes caused by mutations in an unknown nuclear gene.

PMID- 25940036
TI  - Medium-Chain Acyl-CoA Dehydrogenase Deficiency: Evaluation of Genotype-Phenotype
      Correlation in Patients Detected by Newborn Screening.
AB  - BACKGROUND: Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is included in
      many newborn screening programmes worldwide. In addition to the prevalent
      mutation c.985A>G in the ACADM gene, potentially mild mutations like c.199T>C are
      frequently found in screening cohorts. There is ongoing discussion whether this
      mutation is associated with a clinical phenotype. METHODS: In 37 MCADD patients
      detected by newborn screening, biochemical phenotype (octanoylcarnitine (C8),
      ratios of C8 to acetylcarnitine (C2), decanoylcarnitine (C10) and
      dodecanoylcarnitine (C12) at screening and confirmation) and clinical phenotype
      (inpatient emergency treatment, metabolic decompensations, clinical assessments,
      psychometric tests) were assessed in relation to genotype. RESULTS: 16 patients
      were homozygous for c.985A>G (group 1), 11 compound heterozygous for c.199T>C and
      c.985A>G/another mutation (group 2) and 7 compound heterozygous for c.985A>G and
      mutations other than c.199T>C (group 3) and 3 carried neither c.985A>G nor
      c.199T>C but other known homozygous mutations (group 4). At screening C8/C2 and
      C8/C10, at confirmation C8/C2, C8/C10 and C8/C12 differed significantly between
      patients compound heterozygous for c.199T>C (group 2) and other genotypes. C8,
      C10 and C8/C2 at screening were strongly associated with time of sampling in
      groups 1 + 3 + 4, but not in group 2. Clinical phenotype did not differ between
      genotypes. Two patients compound heterozygous for c.199T>C and a severe mutation
      showed neonatal decompensation with hypoglycaemia. CONCLUSION: Biochemical
      phenotype differs between MCADD patients compound heterozygous for c.199T>C with
      a severe mutation and other genotypes. In patients detected by newborn screening,
      clinical phenotype does not differ between genotypes following uniform treatment
      recommendations. Neonatal decompensation can also occur in patients with the
      presumably mild mutation c.199T>C prior to diagnosis.

PMID- 25940037
TI  - Biomarkers for polycyclic aromatic hydrocarbons and serum liver enzymes.
AB  - BACKGROUND: Limited evidence suggests that human liver toxicity is associated
      with exposure to polycyclic aromatic hydrocarbons (PAHs). METHODS: The
      association of urinary PAH metabolites with serum liver enzymes was tested among
      288 workers at a petrochemical plant, using a general linear model (GLM) and
      multiple logistic regression. RESULTS: Urine 2-naphthol levels were positively
      correlated with serum AST after adjustment for covariates in GLM. Comparing third
      tertile versus first tertile of 2-naphthol levels, the odds ratios (OR) were
      elevated for abnormal serum AST levels [OR = 4.1 (95%CI 1.6-10.2)] and abnormal
      serum ALT levels [OR = 2.4 (95%CI 1.2-4.9)]. CONCLUSIONS: Although confounding by
      alcohol intake was not completely ruled out, our findings demonstrate an
      association between PAHs exposure and elevation in serum liver enzymes. Urinary 2
      naphthol is a biomarker of exposure to PAHs that is associated with liver
      toxicity.

PMID- 25940039
TI  - The relationship between mother to child calories served and maternal perception
      of hunger.
AB  - BACKGROUND: Research has examined self-serving portions in adults and children
      and has shown that larger portion size is related to more calories consumed. The
      present study examines factors that may influence the portion sizes a mother
      serves her child at a mealtime. METHODS: The present observational study included
      a community-based sample of 29 mother-child dyads. Dyads attended a 1-h session
      in which they shared a meal together. A buffet of food was provided and the
      mother was asked to serve her child and herself. The amount of food served and
      consumed by the child was recorded. Main independent variables of interest
      included maternal body mass index (BMI), child BMI Z-score, and maternal
      perception of personal and child hunger. The primary dependent variable was the
      total calories the mother served her child. Regression models and a moderated
      mediation were used to examine the relation between variables. RESULTS: Calories
      served to the child was positively associated with calories consumed by the
      child. Maternal perception of her own hunger was related to her perception of her
      child's hunger. Furthermore, maternal perception of child hunger explained the
      relationship between maternal perception of personal hunger and total calories
      served to the child, although only for obese mothers. CONCLUSIONS: Mothers may be
      serving their children larger portion sizes based on their personal weight and
      their perception of their child's hunger. To help children obtain or maintain a
      healthy weight, obesity prevention and intervention programmes should help
      mothers serve more appropriate serving sizes to their children.

PMID- 25940038
TI  - Grief and Traumatic Grief in Children in the Context of Mass Trauma.
AB  - Children who have had someone close die as a result of a mass trauma event such
      as war, armed conflict, acts of terror, political violence, torture, mass
      accidents, and natural disasters are at risk for biopsychosocial problems.
      Research on how to classify when grief becomes complicated or traumatic in
      children is scarce, and while functioning level may provide a good indication,
      assessing functioning may be difficult in mass trauma environments where routines
      and structure are often lacking. There are promising trauma- and grief-focused
      interventions for children post-mass trauma, which are mostly provided in school
      settings. However, more advanced multi-method interventions are needed that
      address grief and trauma in the context of the child's overall mental health,
      parent/caregiver role in assisting the child, family system issues, ways to
      provide safe caring environments amidst chaos and change, and interventions that
      take into account local consumer perspectives, including the voices of children. 

PMID- 25940040
TI  - Arrhenius activation energy of damage to catalase during spray-drying.
AB  - The inactivation of catalase during spray-drying over a range of outlet gas
      temperatures could be closely represented by the Arrhenius equation. From this an
      activation energy for damage to the catalase could be calculated. The close fit
      to Arrhenius suggests that the thermally-induced part of inactivation of the
      catalase during the complex drying and particle-formation processes takes place
      at constant temperature. These processes are rapid compared with the residence
      time of the powder in the collecting vessel of the cyclone where dried catalase
      is exposed to a constant temperature equal to approximately the drying gas outlet
      temperature. A lower activation energy after spray drying with the ultrasonic
      nozzle was found than with the 2-fluid nozzle under otherwise identical spray
      drying conditions. It is feasible that the ultrasonic nozzle when mounted in the
      lid of the spray dryer heats up toward the drying gas inlet temperature much more
      that the air-cooled 2-fluid nozzle. Calculation of the Arrhenius activation
      energy also showed how the stabilizing efficacy of trehalose and mannitol on the
      catalase varies in strength across the range of drying gas inlet and outlet
      temperatures examined. 

PMID- 25940041
TI  - Reversible hydrophobic ion-paring complex strategy to minimize acylation of
      octreotide during long-term delivery from PLGA microparticles.
AB  - Acylation of peptide has been reported for a number of peptides and proteins
      during release from polymers comprising of lactide and glycolide. We hypothesize
      that reversible hydrophobic ion-pairing (HIP) complex may minimize octreotide
      acylation during release. Sodium dodecyl sulfate (SDS), dextran sulfate A (DSA,
      Mw 9-20 kDa) and dextran sulfate B (DSB, Mw 36-50 kDa) were selected as ion
      pairing agents to prepare reversible HIP complex with octreotide. Complexation
      efficiency was optimized with respect to the mole ratio of ion-pairing agent to
      octreotide to achieve 100% complexation of octreotide. Dissociation studies
      suggested that DSA-octreotide and DSB-octreotide complexes dissociate completely
      at physiological pH in presence of counter ions unlike SDS-octreotide complex.
      DSA-octreotide and DSB-octreotide complex encapsulated PLGA microparticles
      (DSAMPs and DSBMPs) were prepared using the S/O/W emulsion method. Entrapment
      efficiencies for DSAMPs and DSBMPs were 74.7+/-8.4% and 81.7+/-6.3%,
      respectively. In vitro release of octreotide was performed by suspending MPs in
      gel. A large fraction of peptide was released in chemically intact form and <7%
      was acylated from DSAMPs and DSBMPs in gel over 55 days. Therefore, HIP
      complexation could be a viable strategy to minimize acylation of peptides and
      proteins during extended release from lactide and glycolide based polymers.

PMID- 25940042
TI  - Potential of hydrogel-forming and dissolving microneedles for use in paediatric
      populations.
AB  - Development of formulations and drug delivery strategies for paediatric use is
      challenging, partially due to the age ranges within this population, resulting in
      varying requirements to achieve optimised patient outcomes. Although the oral
      route of drug delivery remains the preferred option, there are problematic
      issues, such as difficulty swallowing and palatability of medicines specific to
      this population. The parenteral route is not well accepted by children due to
      needle-related fear and pain. Accordingly, a plethora of alternative routes of
      drug administration have been investigated. Microneedles (MN) breach the stratum
      corneum (SC), the outermost layer of skin, increasing the number of drug
      substances amenable to transdermal delivery. This strategy involves the use of
      micron-sized needles to painlessly, and without drawing blood, create transient
      aqueous conduits in the SC. In this study, polymeric dissolving MN and hydrogel
      forming MN were fabricated incorporating two model drugs commonly used in
      paediatric patients (caffeine and lidocaine hydrochloride). The potential
      efficacy of these MN for paediatric dosing was investigated via in vitro and in
      vivo studies. Views pertaining to MN technology were sought amongst school
      children in Northern Ireland, members of the UK general public and UK-based
      paediatricians, to determine perceived benefits, acceptance, barriers and
      concerns for adoption of this technology. In this study, polymeric MN were shown
      to substantially enhance skin permeability of the model therapeutic molecules in
      vitro and in vivo. In particular, hydrogel-forming MN led to a 6.1-fold increase
      in caffeine delivery whilst lidocaine HCl delivery was increased by 3.3-fold
      using dissolving MN in vitro. Application of caffeine-loaded MN led to a caffeine
      plasma concentration of 23.87 MUg/mL in rats at 24 h. This research also
      highlighted a strong consensus regarding MN technology amongst schoolchildren,
      paediatricians and the general public, regarding potential use of MN in the
      paediatric population. Overall, 93.6% of general public respondents and 85.9% of
      paediatricians regarded the use of MN as a positive approach.

PMID- 25940043
TI  - Translating the genetics of cystic fibrosis to personalized medicine.
AB  - Cystic fibrosis (CF) is the most common life-threatening recessive genetic
      disease in the Caucasian population. This multiorgan disease is caused by
      mutations in the gene encoding the CF transmembrane conductance regulator (CFTR)
      protein, a chloride channel recognized as regulating several apical ion channels.
      The gene mutations result either in the lack of the protein at the apical surface
      or in an improperly functioning protein. Morbidity and mortality because of the
      mutation of CFTR are mainly attributable to lung disease resulting from chronic
      infection and inflammation. Since its discovery as the causative gene in 1989,
      much progress has been achieved not only in clinical genetics but also in basic
      science studies. Recently, combinations of these efforts have been successfully
      translated into development and availability for patients of new therapies
      targeting specific CFTR mutations to correct the CFTR at the protein level.
      Current technologies such as next gene sequencing and novel genomic editing tools
      may offer new strategies to identify new CFTR variants and modifier genes, and to
      correct CFTR to pursue personalized medicine, which is already developed in some
      patient subsets. Personalized medicine or P4 medicine ("personalized,"
      "predictive," "preventive," and "participatory") is currently booming for CF. The
      various current and future challenges of personalized medicine as they apply to
      the issues faced in CF are discussed in this review. 

PMID- 25940044
TI  - Circulating microRNAs: novel biomarkers for early detection of colorectal cancer.

PMID- 25940045
TI  - Customer satisfaction, taking care of the loved ones in a time of crisis.

PMID- 25940046
TI  - All About JEN-And More.

PMID- 25940047
TI  - Building on our collaborative efforts for the future of children.

PMID- 25940048
TI  - Use of four-factor prothrombin complex concentrate in the emergency department.

PMID- 25940049
TI  - Multidisciplinary team to achieve low blood culture contamination rates in health
      care facilities.

PMID- 25940050
TI  - The flaws of "herd immunity": whose duty is it to protect the very young/old,
      pregnant, vaccine allergic, and the immunosuppressed?

PMID- 25940051
TI  - ED Flow Coordinators.

PMID- 25940052
TI  - Response.

PMID- 25940054
TI  - Emergency Nursing Review Questions: May 2015: Review questions and answers on
      topics about which nurses should be knowledgeable.

PMID- 25940053
TI  - A 37-year-old man with chronic low back pain and substance abuse.

PMID- 25940055
TI  - Human papillomavirus mRNA testing for the detection of anal high-grade squamous
      intraepithelial lesions in men who have sex with men infected with HIV.
AB  - Currently, screening for anal high-grade squamous intraepithelial lesions (anal
      HSIL) relies on anal cytology and high-resolution anoscopy. Since this approach
      has limited sensitivity and specificity for detecting anal HSIL, there is
      increasing interest in the role of biomarkers for predicting anal HSIL. The aim
      of this study is to evaluate the diagnostic accuracy of HPV E6/E7-mRNA expression
      for the detection of anal HSIL in MSM infected with HIV, in comparison to DNA-HR
      HPV and anal cytology. This cross-sectional screening study included 101 MSM
      followed at the HIV-unit of La Paz University Hospital. Intra-anal swabs from
      patients participating in a screening program including cytology, high-resolution
      anoscopy and histology were analyzed. HR-HPV-DNA detection was performed by means
      of the CLART(r) HPV2 assay (GENOMICA S.A.U., Madrid, Spain). E6/E7-mRNA detection
      of HR-HPV-types 16, 18, 31, 33, and 45 was performed using the NucliSENS-EasyQ
      assay (BioMerieux, Marcy lEtoile, France). HR-HPV DNA and HPVE6/E7 mRNA were
      detected in 82% and 57% of the anal smears respectively. Anal cytology screening
      was abnormal in 70.3%. For the detection of HSIL sensitivity, specificity,
      positive predictive value (PPV), and negative predictive value (NPV) were 71.7%,
      55.6%, 57.9%, and 69.8% for E6/E7-mRNA testing, respectively, compared to 100%,
      31.5%, 55.4%, and 100% for HR-HPV-DNA testing and to 83%, 40.7%, 54.9%, 73.3% of
      cytology testing. In comparison with the other tests, HPVE6/E7 mRNA testing
      yielded a lower clinical sensitivity but a higher clinical specificity and PPV
      for the detection of anal HSIL in MSM infected with HIV.

PMID- 25940057
TI  - Regional thrombolysis with tenecteplase during extracorporeal membrane
      oxygenation: a new approach for left ventricular thrombosis.
AB  - We present the case of a woman assisted with veno-arterial extracorporeal
      membrane oxygenation (v-a ECMO) for postischemic cardiogenic shock, who developed
      left ventricular thrombosis despite systemic anticoagulation and left ventricular
      apical venting. We successfully achieved local thrombolysis with tenecteplase
      administered through the venting cannula to obtain local thrombolysis while
      reducing systemic effects to a minimum. The procedure was effective with mild
      systemic bleeding and the patient was successfully weaned off the extracorporeal
      support a few days thereafter.

PMID- 25940056
TI  - Speed and complexity characterize attention problems in children with
      localization-related epilepsy.
AB  - OBJECTIVE: Children with epilepsy (EPI) have a higher rate of attention
      deficit/hyperactivity disorder (ADHD; 28-70%) than typically developing (TD)
      children (5-10%); however, attention is multidimensional. Thus, we aimed to
      characterize the profile of attention difficulties in children with epilepsy.
      METHODS: Seventy-five children with localization-related epilepsy ages 6-16 years
      and 75 age-matched controls were evaluated using multimodal, multidimensional
      measures of attention including direct performance and parent ratings of
      attention as well as intelligence testing. We assessed group differences across
      attention measures, determined if parent rating predicted performance on
      attention measures, and examined if epilepsy characteristics were associated with
      attention skills. RESULTS: The EPI group performed worse than the TD group on
      timed and complex attention aspects of attention (p < 0.05), whereas performance
      on simple visual and simple auditory attention tasks was comparable. Children
      with EPI were 12 times as likely as TD children to have clinically elevated
      symptoms of inattention as rated by parents, but ratings were a weak predictor of
      attention performance. Earlier age of onset was associated with slower motor
      speed (p < 0.01), but no other epilepsy-related clinical characteristics were
      associated with attention skills. SIGNIFICANCE: This study clarifies the nature
      of the attention problems in pediatric epilepsy, which may be under-recognized.
      Children with EPI had difficulty with complex attention and rapid response, not
      simple attention. As such, they may not exhibit difficulty until later in primary
      school when demands increase. Parent report with standard ADHD screening tools
      may under-detect these higher-order attention difficulties. Thus, monitoring
      through direct neuropsychological performance is recommended.

PMID- 25940058
TI  - In Search of a Gold Standard Scoring System for the Subjective Evaluation of
      Cosmetic Outcomes Following Breast-Conserving Therapy.
AB  - The absence of a widely accepted method for aesthetic evaluation following breast
      conserving surgery for breast cancer limits the ability to evaluate cosmetic
      outcomes. In this study, two different panel scoring approaches were compared in
      an attempt to identify a gold standard scoring system for subjectively assessing
      cosmetic outcomes following breast-conserving therapy. Standardized photographs
      of each participant were evaluated independently by twelve health care
      professionals involved in breast cancer diagnosis and treatment using the Danoff
      four-point scale. Individual Danoff scores were combined using two methods, a
      random sample "three-panel" score and an iterative "Delphi-panel" score, in order
      to create a final cosmetic score for each patient. Agreement between these two
      aggregative approaches was assessed with a weighted kappa (wk) statistic. Patient
      and professional recruitment occurred at two separate tertiary care multi
      disciplinary breast health centers. Women with unilateral breast cancer who
      underwent breast-conserving therapy (segmental mastectomy or lumpectomy and
      radiotherapy) and were at least 2 years after radiotherapy were asked to
      participate. Ninety-seven women were evaluated. The Delphi approach required
      three rounds of evaluation to obtain greater than 50% agreement in all
      photographs. The wk statistic between scores generated from the "three-panel" and
      "Delphi-panel" approaches was 0.80 (95% CI: 0.71-0.89), thus demonstrating
      substantial agreement. Evaluation of cosmetic outcomes following breast
      conserving therapy using a "three-panel" and "Delphi-panel" score provide similar
      results, confirming the reliability of either approach for subjective evaluation.
      Simplicity of use and interpretation favors the "three-panel" score. Future work
      should concentrate on the integration of the three-panel score with objective and
      patient-reported scales to generate a comprehensive cosmetic evaluation platform.

PMID- 25940059
TI  - The effect of position on esophageal structure and function determined with solid
      state high-resolution manometry.
AB  - OBJECTIVE: To investigate the influence of posture on the anatomy and function of
      esophageal sphincters using solid-state high-resolution manometry. METHODS: Fifty
      individuals underwent esophageal manometry with a 36-channel solid-state catheter
      in the supine and upright positions. The length and pressure of the esophageal
      sphincters, as well as the esophageal and intra-abdominal lengths of lower
      esophageal sphincter (LES), were recorded. The residual pressure of the upper
      esophageal sphincter (UES) and the 4-s integrated relaxation pressure were also
      measured when the participants swallowed 10 consecutive servings of water (5 mL
      each). The Bland-Altman plot was used to assess agreement between these
      parameters in the supine and upright positions. RESULTS: The LES resting pressure
      was significantly decreased in the upright position compared with the supine
      position (13.85 +/- 5.90 mmHg vs 18.09 +/- 7.80 mmHg, P = 0.000). Weaker
      integrated relaxation pressures were observed when the participants were in the
      upright position (5.66 +/- 3.33 mmHg vs 7.80 +/- 3.25 mmHg, P = 0.000). Compared
      with the supine position, the upright esophageal length was longer (P = 0.004)
      and the upper border of the LES was lower (P = 0.050) when the individuals were
      in the upright position. The agreement between the two positions was acceptable
      for the esophageal length, LES upper border location and LES pressure
      measurements. CONCLUSIONS: Body position exerts a greater influence on the LES
      than on the UES. Thus, it is necessary to establish normal values for the LES
      basal pressure and residual pressure in different positions.

PMID- 25940060
TI  - Radial shock wave treatment alone is less efficient than radial shock wave
      treatment combined with tissue-specific plantar fascia-stretching in patients
      with chronic plantar heel pain.
AB  - BACKGROUND: Whether shock wave therapy or shock wave therapy combined with
      plantar fascia-specific stretching is more efficient in treating chronic plantar
      heel pain remains unclear. The aim of the study was to test the null hypothesis
      of no difference of these two forms of management for patients who had unilateral
      plantar fasciopathy for a minimum duration of twelve months and which had failed
      at least three other forms of treatment. METHODS: One hundred and fifty-two
      patients with chronic plantar fasciopathy were assigned to receive repetitive low
      energy radial shock-wave therapy without local anesthesia, administered weekly
      for three weeks (Group 1, n = 73) or to receive the identical shock wave
      treatment and to perform an eight-week plantar fascia-specific stretching program
      (Group 2, n = 79). All patients completed the nine-item pain subscale of the
      validated Foot Function Index and a subject-relevant outcome questionnaire.
      Patients were evaluated at baseline, and at two, four, and twenty-four months
      after baseline. The primary outcome measures were a mean change in the Foot
      Function Index sum score at two months after baseline, a mean change in item 2
      (pain during the first steps of walking in the morning) on this Index, and
      satisfaction with treatment. RESULTS: No difference in mean age, sex, weight or
      duration of symptoms was found between the groups at baseline. At two months
      after baseline, the Foot Function Index sum score showed significantly greater
      changes for the patients managed with shock-wave therapy plus plantar fascia
      specific stretching than those managed with shock-wave therapy alone (p < 0.001),
      as well as individually for item 2 (p < 0.001). Twenty-four patients in Group 1
      (32%) versus forty-seven patients in Group 2 (59%) were satisfied with the
      treatment (p < 0.001). Significant differences persisted at four months, but not
      at twenty-four months. CONCLUSIONS: A program of manual stretching exercises
      specific to the plantar fascia in combination with repetitive low-energy radial
      shock-wave therapy is more efficient than repetitive low-energy radial shock-wave
      therapy alone for the treatment of chronic symptoms of proximal plantar
      fasciopathy.

PMID- 25940062
TI  - Adaptive optics in spinning disk microscopy: improved contrast and brightness by
      a simple and fast method.
AB  - Multiconfocal microscopy gives a good compromise between fast imaging and
      reasonable resolution. However, the low intensity of live fluorescent emitters is
      a major limitation to this technique. Aberrations induced by the optical setup,
      especially the mismatch of the refractive index and the biological sample itself,
      distort the point spread function and further reduce the amount of detected
      photons. Altogether, this leads to impaired image quality, preventing accurate
      analysis of molecular processes in biological samples and imaging deep in the
      sample. The amount of detected fluorescence can be improved with adaptive optics.
      Here, we used a compact adaptive optics module (adaptive optics box for
      sectioning optical microscopy), which was specifically designed for spinning disk
      confocal microscopy. The module overcomes undesired anomalies by correcting for
      most of the aberrations in confocal imaging. Existing aberration detection
      methods require prior illumination, which bleaches the sample. To avoid multiple
      exposures of the sample, we established an experimental model describing the
      depth dependence of major aberrations. This model allows us to correct for those
      aberrations when performing a z-stack, gradually increasing the amplitude of the
      correction with depth. It does not require illumination of the sample for
      aberration detection, thus minimizing photobleaching and phototoxicity. With this
      model, we improved both signal-to-background ratio and image contrast. Here, we
      present comparative studies on a variety of biological samples. 

PMID- 25940061
TI  - Gorlin syndrome and desmoplastic medulloblastoma: Report of 3 cases with
      unfavorable clinical course and novel mutations.
AB  - We present three cases of genetically confirmed Gorlin syndrome with desmoplastic
      medulloblastoma (DMB) in whom tumor recurred despite standard therapy. One
      patient was found to have a novel germline missense PTCH1 mutation. Molecular
      analysis of recurrent tumor using fluorescent in situ hybridization (FISH)
      revealed PTEN and/ or PTCH1 loss in 2 patients. Whole exome sequencing (WES) of
      tumor in one patient revealed loss of heterozygosity of PTCH1 and a mutation of
      GNAS gene in its non-coding 3' -untranslated region (UTR) with corresponding
      decreased protein expression. While one patient died despite high-dose
      chemotherapy (HDC) plus stem cell rescue (ASCR) and palliative radiotherapy, two
      patients are currently alive for 18+ and 120+ months respectively following
      retrieval therapy that did not include irradiation. Infants with DMB and GS
      should be treated aggressively with chemotherapy at diagnosis to prevent relapse
      but radiotherapy should be avoided. The use of molecular prognostic markers for
      DMB should be routinely used to identify the subset of tumors that might have an
      aggressive course.

PMID- 25940063
TI  - CT assessment of right colonic arterial anatomy pre and post cancer resection - a
      potential marker for quality and extent of surgery?
AB  - BACKGROUND: There is conflicting opinion as to the optimum extent of resection
      for right-sided colonic cancer, which is currently graded by pathological
      analysis of the resected specimen. It is not known if computed tomography (CT)
      analysis of residual post-resection arterial stump length could be used as an
      alternative in vivo marker for extent of mesenteric resection. Ileocolic artery
      stumps have been demonstrated previously on CT after right hemicolectomy, but
      only in the early postoperative period. PURPOSE: To analyze preoperative right
      colonic arterial anatomy using portal venous colorectal cancer staging CT and
      subsequently determine if post-resection arterial stumps (a potential in vivo
      marker of surgical resection) could be consistently identified using routine
      follow-up CT scans many months after cancer resection. MATERIAL AND METHODS: A
      retrospective analysis of routine staging and follow-up CT scans for 151 patients
      with right-sided colorectal cancer was performed. Preoperative right colonic
      arterial anatomy and postoperative arterial stumps were analyzed and measured.
      RESULTS: Preoperative ileocolic (98.8%), middle (94.7%), and right colic artery
      (23.8%) identification was comparable to catheter angiogram studies.
      Postoperative ileocolic stumps were consistently demonstrated (88.3%) many months
      (average, 2 years and 42 days) after resection and were significantly longer than
      expected for a standard D2 resection (paired t-test, t(127) = -11.45, P <=
      0.001). CONCLUSION: This is the first study to successfully demonstrate ileocolic
      arterial stumps many months (and years) after cancer resection using routine
      portal venous CT. Further prospective research should assess whether arterial
      stumps can be used as an in vivo marker of surgical quality and extent.

PMID- 25940064
TI  - Bilateral total hip replacement: periprosthetic pseudotumor collections are more
      prevalent in metal-on-metal implants compared to non-metal-on-metal ones.
AB  - BACKGROUND: Metal-on-metal (MoM) hip prostheses were shown to have high failure
      rates including the formation of periprosthetic cystic masses called
      periprosthetic pseudotumor collections (PPCs). PURPOSE: To compare MRI prevalence
      and size of PPCs in patients after bilateral total-hip-replacement (THR) in which
      at least one hip was replaced by a MoM prosthesis. MATERIAL AND METHODS: All
      sequential MRI examinations of patients with bilateral THR in which at least one
      is MoM (2010-2013) were retrospectively evaluated. MRIs were analyzed separately
      by two readers for the presence and size of PPCs. These were compared between MoM
      and non-MoM implants and between patients with unilateral or bilateral-MoM
      prostheses. Blood metal ion levels were also compared. RESULTS: Seventy hips of
      35 patients (male:female ratio, 9:26; mean age, 64 years; age range, 35-82 years)
      were assessed. Sixteen patients (45%) underwent bilateral MoM-THRs and 19 (55%)
      had one MoM and the other non-MoM, yielding 51 MoM THRs and 19 non-MoM THRs.
      Twenty-eight PPCs were detected in 19 patients (54%): 26 in MoM THRs (51%) and
      two in non-MoM THRs (10.5%, P = 0.00009). The mean PPC volume in the MoM implants
      (107 mm(3)) was higher than that of the non-MoM implants (18 mm(3), P = 0.49).
      Cobalt/chromium blood levels were 78 ug/L/25 ug/L for bilateral MoM THRs and 21
      ug/L/10 ug/L for unilateral MoM implants (P = 0.1 and 0.16, respectively).
      CONCLUSION: PPCs are more prevalent in MoM THRs compared to non-MoM THRs. Larger
      PPC volumes and higher blood metal ion levels were detected in patients with
      bilateral MoM THRs compared to unilateral MoM THRs (P > 0.05).

PMID- 25940065
TI  - Business, but not as usual.

PMID- 25940066
TI  - Tandem rhodium catalysis: exploiting sulfoxides for asymmetric transition-metal
      catalysis.
AB  - Sulfoxides are uncommon substrates for transition-metal catalysis due to their
      propensity to inhibit catalyst turnover. In a collaborative effort with Ken Houk,
      we developed the first dynamic kinetic resolution (DKR) of allylic sulfoxides
      using asymmetric rhodium-catalyzed hydrogenation. A detailed mechanistic analysis
      of this transformation using both experimental and theoretical methods revealed
      rhodium to be a tandem catalyst that promoted both hydrogenation of the alkene
      and racemization of the allylic sulfoxide. Using a combination of deuterium
      labelling and DFT studies, a novel mode of allylic sulfoxide racemization via a
      Rh(III)-pi-allyl intermediate was identified.

PMID- 25940067
TI  - Incidence and Predictors of Pacemaker Implantation in Patients Undergoing
      Transcatheter Aortic Valve Replacement.
AB  - BACKGROUND: Transcatheter aortic valve replacement (TAVR) has emerged as an
      alternative treatment for patients with symptomatic aortic stenosis who are at
      high risk for surgical aortic valve replacement. The development of conduction
      abnormalities is a major complication in the postprocedural period of TAVR.
      OBJECTIVES: The objective of this study was to investigate the development of
      postprocedural conduction abnormalities and the requirement of permanent
      pacemaker (PPM) implantation in patients undergoing TAVR. METHODS: Data from 137
      consecutive patients who underwent TAVR (Edwards SAPIEN valve, Edwards
      Lifesciences, Irvine, CA, USA) between June 2008 and October 2012 were reviewed.
      Patients with prior history of PPM (n = 27) were excluded. The role of various
      predictors for pacemaker implantation after TAVR, including the valve index
      (calculated as [valve size/left ventricular outflow tract diameter] * 100) was
      investigated. RESULTS: A total of 31/110 (28.2%) patients required implantation
      of a PPM after TAVR. The median time to implantation of a PPM was 5 days after
      the procedure. The development of postprocedural complete heart block was the
      most common indication for implantation of a PPM (16/31; 51.6%). On multivariate
      analysis, the presence of preexisting right bundle branch block (RBBB) was found
      to be a strong predictor of PPM implantation after TAVR (adjusted odds ratio:
      4.87; 95% confidence interval: 1.29-18.46, P = 0.020). Using the receiver
      operated curve analysis, a cut-off value of valve index of 128 was found to be a
      strong predictor for PPM implantation with a sensitivity of 73% and specificity
      of 61% (c statistic = 0.68). CONCLUSIONS: This study identified the presence of
      prior RBBB and a valve index of 128 as important risk factors for PPM
      implantation after TAVR. A larger implanted valve size relative to left
      ventricular outflow tract diameter leads to a greater compression of the
      intrinsic conduction system, increasing the need for pacemaker placement.

PMID- 25940068
TI  - The Second to Fourth Digit Ratio in Acne Vulgaris.
AB  - BACKGROUND: Androgen hormones are thought to play a leading role in acne vulgaris
      (AV). The 2D:4D digit ratio refers to the ratio of the length of the second
      finger (index finger) to that of the fourth finger (ring finger). It is thought
      that the balance between fetal testosterone and fetal estrogen during the
      prenatal period largely determines this ratio, which does not change with age in
      the postnatal period. METHODS: Patients with no other disease except AV and a
      control group of healthy patients were included in the study. Sex, age, family
      history, age of onset, and duration of disease in patients diagnosed with AV were
      recorded. The lengths of the patients' second and fourth fingers were measured
      using a digital caliper with a resolution of 0.01 mm. Hormone levels were also
      measured. RESULTS: When the 2D:4D ratio for the right hand and the left hand
      (separately) as well as the average (mean) 2D:4D ratio of both hands in male and
      female patients were compared with those of the control group, no statistically
      significant difference was observed. The right 2D:4D ratio of female patients was
      positively correlated with free androgen index percentage and prolactin values
      and negatively correlated with sex hormone-binding globulin. The left 2D:4D ratio
      of female patients was found to be positively correlated with disease duration
      and follicle-stimulating hormone values. CONCLUSION: The 2D:4D ratio was not
      significantly different between the group with AV and the control group
      independent of sex. Also, we did not observe a significant association with age
      of onset, severity of disease, or family history.

PMID- 25940069
TI  - A Binary Genetic Approach to Characterize TRPM5 Cells in Mice.
AB  - Transient receptor potential channel subfamily M member 5 (TRPM5) is an important
      downstream signaling component in a subset of taste receptor cells making it a
      potential target for taste modulation. Interestingly, TRPM5 has been detected in
      extra-oral tissues; however, the function of extra-gustatory TRPM5-expressing
      cells is less well understood. To facilitate visualization and manipulation of
      TRPM5-expressing cells in mice, we generated a Cre knock-in TRPM5 allele by
      homologous recombination. We then used the novel TRPM5-IRES-Cre mouse strain to
      report TRPM5 expression by activating a tauGFP transgene. To confirm faithful
      coexpression of tauGFP and TRPM5 we generated and validated a new anti-TRPM5
      antiserum enabling us to analyze acute TRPM5 protein expression. tauGFP cells
      were found in taste bud cells of the vallate, foliate, and fungiform papillae as
      well as in the palate. We also detected TRPM5 expression in several other tissues
      such as in the septal organ of Masera. Interestingly, in the olfactory epithelium
      of adult mice acute TRPM5 expression was detected in only one (short microvillar
      cells) of two cell populations previously reported to express TRPM5. The TRPM5-IC
      mouse strain described here represents a novel genetic tool and will facilitate
      the study and tissue-specific manipulation of TRPM5-expressing cells in vivo. 

PMID- 25940070
TI  - Here today, gone tomorrow: Short-term retention of pesticide-induced tolerance in
      amphibians.
AB  - Pesticide use has led to the ubiquitous contamination of natural habitats, which
      has inadvertently increased pesticide tolerance in target and nontarget species.
      Historically, increased pesticide tolerance has been attributed to natural
      selection for tolerance among individuals of affected populations. Recent
      research, however, has discovered that pesticide tolerance can be increased
      through phenotypic plasticity. Although induced pesticide tolerance may benefit
      organisms experiencing contaminated systems, little is known about its occurrence
      in vertebrates, its retention through ontogeny, or potential life history
      tradeoffs. Using time-to-death assays at 2 distinct developmental windows, the
      authors discovered that gray treefrog (Hyla versicolor) tadpoles exposed to
      sublethal concentrations (0 mg a.i./L, 0.5 mg a.i./L, and 1.0 mg a.i./L) of the
      insecticide Sevin(r) (carbaryl) early in life increased their pesticide tolerance
      to a lethal carbaryl concentration 5 d after sublethal exposure. However, this
      increased tolerance was not retained later in ontogeny (23 d post-sublethal
      exposure). Moreover, no indication was found of pesticide-induced treefrogs
      experiencing life-history tradeoffs in terms of survival to metamorphosis, mass,
      or snout-vent length. Gray treefrogs are only the second vertebrate species and
      the second amphibian family to exhibit pesticide-induced tolerance after
      sublethal exposure. The authors' data suggest that the ability to induce
      increased pesticide tolerance may play a critical role in amphibian survival in
      contaminated ecosystems. However, future work is needed to test the occurrence of
      inducible pesticide tolerance among numerous amphibian populations worldwide.

PMID- 25940071
TI  - Cerebral nitric oxide represses choroid plexus NFkappaB-dependent gateway
      activity for leukocyte trafficking.
AB  - Chronic neuroinflammation is evident in brain aging and neurodegenerative
      disorders and is often associated with excessive nitric oxide (NO) production
      within the central nervous system (CNS). Under such conditions, increased NO
      levels are observed at the choroid plexus (CP), an epithelial layer that forms
      the blood-cerebrospinal fluid barrier (BCSFB) and serves as a selective gateway
      for leukocyte entry to the CNS in homeostasis and following injury. Here, we
      hypothesized that elevated cerebral NO levels interfere with CP gateway activity.
      We found that induction of leukocyte trafficking determinants by the CP and
      sequential leukocyte entry to the CSF are dependent on the CP epithelial
      NFkappaB/p65 signaling pathway, which was inhibited upon exposure to NO.
      Examining the CP in 5XFAD transgenic mouse model of Alzheimer's disease (AD-Tg)
      revealed impaired ability to mount an NFkappaB/p65-dependent response. Systemic
      administration of an NO scavenger in AD-Tg mice alleviated NFkappaB/p65
      suppression at the CP and augmented its gateway activity. Together, our findings
      identify cerebral NO as a negative regulator of CP gateway activity for immune
      cell trafficking to the CNS. 

PMID- 25940073
TI  - Spinach RNA aptamer detects lead(II) with high selectivity.
AB  - Spinach RNA aptamer contains a G-quadruplex motif that serves as a platform for
      binding and fluorescence activation of a GFP-like fluorophore. Here we show that
      Pb(2+) induces formation of Spinach's G-quadruplex and activates fluorescence
      with high selectivity and sensitivity. This device establishes the first example
      of an RNA-based sensor that provides a simple and inexpensive tool for Pb(2+)
      detection. 

PMID- 25940072
TI  - Adaptation of avian influenza A (H6N1) virus from avian to human receptor-binding
      preference.
AB  - The receptor-binding specificity of influenza A viruses is a major determinant
      for the host tropism of the virus, which enables interspecies transmission. In
      2013, the first human case of infection with avian influenza A (H6N1) virus was
      reported in Taiwan. To gather evidence concerning the epidemic potential of H6
      subtype viruses, we performed comprehensive analysis of receptor-binding
      properties of Taiwan-isolated H6 HAs from 1972 to 2013. We propose that the
      receptor-binding properties of Taiwan-isolated H6 HAs have undergone three major
      stages: initially avian receptor-binding preference, secondarily obtaining human
      receptor-binding capacity, and recently human receptor-binding preference, which
      has been confirmed by receptor-binding assessment of three representative virus
      isolates. Mutagenesis work revealed that E190V and G228S substitutions are
      important to acquire the human receptor-binding capacity, and the P186L
      substitution could reduce the binding to avian receptor. Further structural
      analysis revealed how the P186L substitution in the receptor-binding site of HA
      determines the receptor-binding preference change. We conclude that the human
      infecting H6N1 evolved into a human receptor preference. 

PMID- 25940074
TI  - Role of ventricular assist therapy for patients with heart failure and
      restrictive physiology: Improving outcomes for a lethal disease.
AB  - BACKGROUND: Restrictive cardiomyopathy (RCM) patients have poor prognosis due to
      progressive heart failure characterized by impaired ventricular filling of either
      or both ventricles. The goal of this study was to evaluate the outcome of end
      stage RCM patients after left ventricular assist device (LVAD) implantation and
      to determine factors that may be associated with improved survival. METHODS: This
      investigation is a retrospective study of prospectively collected data that
      include 28 consecutive patients with end-stage RCM who received continuous-flow
      LVADs at the Mayo Clinic, Rochester, Minnesota. Outcome was assessed by survival
      with LVAD support until heart transplantation or all-cause mortality. RESULTS:
      The mean follow-up time post-LVAD implantation was 448 +/- 425 days. The mean
      hospitalization time was 29 +/- 19 days and was complicated mainly by post
      operative right ventricular (RV) failure requiring short-term medical support.
      The short-term in-hospital mortality was 14%. Ten patients underwent heart
      transplantation with 100% survival post-transplant during the follow-up period.
      One-year survival for patients with LVADs without transplantation was 64%, and
      was not significantly different between amyloidosis and non-amyloidosis patients.
      Larger left ventricle (LV) end-diastolic and end-systolic dimensions were
      significantly associated with improved survival rates (RR = 0.94 and 0.95, p <
      0.05, respectively), and left ventricular end-diastolic diameter (LVEDD) <=46 mm
      was associated with increased mortality post-LVAD implantation. CONCLUSIONS: LVAD
      is a feasible, life-saving therapy for end-stage heart failure related to RCM,
      especially as a bridge to transplant and in patients with larger LV dimensions.

PMID- 25940076
TI  - Postoperative pulmonary function and complications in living-donor lobectomy.
AB  - BACKGROUND: Successful living-donor lobar lung transplantation largely depends on
      the donor's outcome. Because surgical skills and peri-operative management have
      evolved over time, this study evaluated the recent outcomes of donor lobectomies.
      METHODS: Between 2008 and 2014, 48 consecutive living-donor lobar lung
      transplantations with 85 donor lobectomies were performed at Kyoto University.
      All donors were prospectively followed up regularly until 1 year after surgery.
      RESULTS: Right and left lower lobectomies were performed in 49 and 36 donors,
      respectively. Pulmonary arterial branches were sacrificed at equal frequency in
      both lobectomies, whereas pulmonary arterioplasty was only performed in left
      lower lobectomy (n = 9). All donors were discharged after the lobectomies, and
      none died during follow-up. Post-operative complications occurred in 24 donors
      (28%) overall, without a significant difference between donor sides.
      Intraoperative complications were found in 2 donors. Early and late post
      operative complications were noted in 17 and 6 donors, respectively.
      Pneumothorax, pleuritis, and pleural effusion were the most frequent. Post
      operative pulmonary function sequentially recovered more than expected and was
      not significantly affected by the sacrifice of pulmonary arterial branches during
      lobectomy. By contrast, pulmonary function at 1 year after donor lobectomy in the
      donors who had peri-operative complications was significantly lower than that in
      the donors who did not, although even post-operative pulmonary function in the
      donors with peri-operative complications still recovered more than expected.
      CONCLUSIONS: Living-donor lobectomies have been safely performed in recent
      decades with low morbidities and without mortality.

PMID- 25940075
TI  - Incremental and independent value of cardiopulmonary exercise test measures and
      the Seattle Heart Failure Model for prediction of risk in patients with heart
      failure.
AB  - BACKGROUND: Multivariable risk scores and exercise measures are well-validated
      risk prediction methods. Combining information from a functional evaluation and a
      risk model may improve accuracy of risk predictions. We analyzed whether adding
      exercise measures to the Seattle Heart Failure Model (SHFM) improves risk
      prediction accuracy in systolic heart failure. METHODS: We used a sample of
      patients from the Heart Failure and A Controlled Trial Investigating Outcomes of
      Exercise TraiNing (HF-ACTION) study (http://www.clinicaltrials.gov; unique
      identifier: NCT00047437) to examine the addition of peak oxygen consumption,
      expired volume per unit time/volume of carbon dioxide slope, 6-minute walk
      distance, or cardiopulmonary exercise duration to the SHFM. Multivariable Cox
      proportional hazards models were used to test the association between the
      combined end point (death, left ventricular assist device, or cardiac
      transplantation) and the addition of exercise variables to the SHFM. RESULTS: The
      sample included 2,152 patients. The SHFM and all exercise measures were
      associated with events (all p < 0.0001) in proportional hazards models. There was
      statistically significant improvement in risk estimation when exercise measures
      were added to the SHFM. However, the improvement in the C index for the addition
      of peak volume of oxygen consumption (+0.01), expired volume per unit time/volume
      of carbon dioxide slope (+0.02), 6-minute walk distance (-0.001), and
      cardiopulmonary exercise duration (+0.001) to the SHFM was small or slightly
      worse than the SHFM alone. Changes in risk assignment with the addition of
      exercise variables were minimal for patients above or below a 15% 1-year
      mortality. CONCLUSIONS: Exercise performance measures and the SHFM are
      independently useful for predicting risk in systolic heart failure. Adding
      cardiopulmonary exercise testing measures and 6MWD to the SHFM offers only
      minimal improvement in risk reassignment at clinically meaningful cut points.

PMID- 25940077
TI  - Influence of cytomegalovirus infection in the development of cardiac allograft
      vasculopathy after heart transplantation.
AB  - BACKGROUND: Cardiac allograft vasculopathy (CAV) is a major cause of long-term
      morbidity and mortality after heart transplantation (HTx), whose relationship
      with CMV infection is uncertain. This study evaluated the influence of CMV
      infection in the development of CAV. METHODS: We enrolled 166 consecutive HTx
      recipients who underwent their first transplant from January 1995 to July 2002.
      All patients received 14 days of intravenous ganciclovir and were prospectively
      monitored for CMV infection during the first year after HTx. CAV was diagnosed by
      coronary angiography performed at 1, 5, and 10 years after HTx, following the new
      criteria of the International Society for Heart and Lung Transplantation. We
      collected all variables potentially related with the development of CAV. Risk
      factors were studied using a complementary log-log model. RESULTS: After a median
      follow-up of 11 years (range, 1-17 years), 72 patients (43%) developed CAV (63.8%
      CAV(1), 15.2% CAV(2), 20.8% CAV(3)). Symptoms secondary to CAV were present in
      32% of these patients, and 8% died because of it. In the regression multivariate
      analysis, independent variables associated with the development of CAV were donor
      age (hazard ratio [HR], 1.028; 95% confidence interval [CI], 1.002-1.053; p <
      0.028), presence of cellular acute rejection >= 2R (HR, 1.764; 95% CI, 1.011
      3.078; p < 0.0414), CMV infection (HR, 2.334; 95% CI, 1.043-5.225; p < 0.0354),
      and not having been treated with a calcium channel blocker (HR, 0.472; 95% CI,
      0.275-0.811; p < 0.0055). CONCLUSIONS: Standardized angiographic criteria show
      CMV infection is associated with the development of CAV.

PMID- 25940078
TI  - Big data for a rare disease: Examining heart transplantation for left ventricular
      noncompaction in the United Network of Organ Sharing registry.

PMID- 25940079
TI  - Reply: Effect of racial and ethnic differences in heart transplantation with ABO
      incompatibility.

PMID- 25940081
TI  - Facile synthesis of graphene-CeO2 nanocomposites with enhanced electrochemical
      properties for supercapacitors.
AB  - Graphene-ceria (CeO2G) nanocomposites were prepared by using a low-temperature
      solution process with different weight percentages of graphene, and their
      electrochemical properties were investigated. Structural properties of the
      nanocomposites were studied by X-ray diffraction, Raman spectroscopy, and FTIR
      spectral analyses. FE-SEM and HRTEM images revealed a "wrinkled paper"-like
      morphology of the prepared composites. Elemental mapping images were recorded by
      using the FE-EPMA technique. XPS analyses revealed the binding states of
      different elements present in the composites. The composite with 5% graphene
      displayed a specific capacitance of 110 F g(-1), according to cyclic voltammetric
      studies, which is higher than that observed for pure CeO2 (75 F g(-1)). The
      significant increase in the specific capacitance suggests that the CeO2G is a
      promising material for supercapacitor applications. 

PMID- 25940080
TI  - Herpes zoster-associated mortality in Europe: a systematic review.
AB  - BACKGROUND: Reactivation of latent varicella zoster virus, partly due to age
      related immunosenescence and immunosuppressive conditions, results in herpes
      zoster (HZ) and its associated complications. The management of the most
      important complication, post-herpetic neuralgia (PHN), is challenging,
      particularly in the elderly, and is generally unsatisfactory. No previous reviews
      have reported the incidence of HZ-associated mortality. METHODS: We carried out a
      systematic literature review to identify studies and databases providing data for
      HZ-associated mortality in adults aged >= 50 years in Europe. RESULTS: We
      identified 12 studies: Belgium (1); France (1); Germany (1); the Netherlands (2);
      Portugal (1); Spain (4) and England/Wales (2) and 4 databases from Europe:
      France; Germany and England/Wales. The incidence was available from eight
      studies; it was highest in those aged >= 95 in France (19.48/100,000). In the
      European (WHO) database, the overall mortality ranged from 0 to > 0.07/100,000.
      The age- and gender-specific HZ mortality rates from the other databases showed
      that while in younger age groups the HZ mortality rate was higher in males, in
      older patients the rate was much higher in women. The case fatality rate was 2
      and 61/100,000 in those 45-65 and >= 65 years, respectively. A similar increase
      with age was seen for the hospital fatality rate; 0.6% in those 45-65 years in
      the UK and 7.1% in those >= 80 in Spain. CONCLUSIONS: Although the data were
      sparse and heterogeneous, HZ-associated mortality clearly increases with age. In
      addition, the elderly who develop HZ often have underlying diseases and are at
      increased risk of functional decline and loss of independence. Mortality should
      be taken into account in health-economics models.

PMID- 25940082
TI  - In Vitro Testing for Orally Inhaled Products: Developments in Science-Based
      Regulatory Approaches.
AB  - This article is part of a series of reports from the "Orlando Inhalation
      Conference-Approaches in International Regulation" which was held in March 2014,
      and coorganized by the University of Florida and the International Pharmaceutical
      Aerosol Consortium on Regulation and Science (IPAC-RS). The goal of the
      conference was to foster the exchange of ideas and knowledge across the global
      scientific and regulatory community in order to identify and help move towards
      strategies for internationally harmonized, science-based regulatory approaches
      for the development and marketing approval of inhalation medicines, including
      innovator and second entry products. This article provides an integrated
      perspective of case studies and discussion related to in vitro testing of orally
      inhaled products, including in vitro-in vivo correlations and requirements for in
      vitro data and statistical analysis that support quality or bioequivalence for
      regulatory applications. 

PMID- 25940083
TI  - Early Drug Discovery Prediction of Proarrhythmia Potential and Its Covariates.

PMID- 25940085
TI  - Spectroscopic studies of kinetically trapped conformations in the gas phase: the
      case of triply protonated bradykinin.
AB  - Understanding the relation between the gas-phase structure of biological
      molecules and their solution-phase structure is important when attempting to use
      gas-phase techniques to address biologically relevant questions. Directly after
      electrospray ionization, molecules can be kinetically trapped in a state that
      retains some "memory" of its conformation in solution and is separated from the
      lowest-energy gas-phase structure by barriers on the potential energy surface. In
      order to identify and characterize kinetically trapped structures, we have
      explored the conformational space of triply protonated bradykinin in the gas
      phase by combining field-asymmetric ion mobility spectrometry (FAIMS) with cold
      ion spectroscopy. We isolate three distinct conformational families and
      characterize them by recording their UV-photofragment spectra and vibrational
      spectra. Annealing of the initial conformational distribution produced by
      electrospray reveals that one of the conformational families is kinetically
      trapped, while two others are stable, gas-phase structures. We compare our
      results to previously published results obtained using drift-tube ion mobility
      spectrometry (IMS) and propose a correspondence between the conformational
      families separated by FAIMS and those by IMS. 

PMID- 25940084
TI  - Computational Advances for the Development of Allosteric Modulators and Bitopic
      Ligands in G Protein-Coupled Receptors.
AB  - Allosteric modulators of G protein-coupled receptors (GPCRs), which target at
      allosteric sites, have significant advantages against the corresponding
      orthosteric compounds including higher selectivity, improved chemical
      tractability or physicochemical properties, and reduced risk of receptor
      oversensitization. Bitopic ligands of GPCRs target both orthosteric and
      allosteric sites. Bitopic ligands can improve binding affinity, enhance subtype
      selectivity, stabilize receptors, and reduce side effects. Discovering allosteric
      modulators or bitopic ligands for GPCRs has become an emerging research area, in
      which the design of allosteric modulators is a key step in the detection of
      bitopic ligands. Radioligand binding and functional assays ([(35)S]GTPgammaS and
      ERK1/2 phosphorylation) are used to test the effects for potential modulators or
      bitopic ligands. High-throughput screening (HTS) in combination with disulfide
      trapping and fragment-based screening are used to aid the discovery of the
      allosteric modulators or bitopic ligands of GPCRs. When used alone, these methods
      are costly and can often result in too many potential drug targets, including
      false positives. Alternatively, low-cost and efficient computational approaches
      are useful in drug discovery of novel allosteric modulators and bitopic ligands
      to help refine the number of targets and reduce the false-positive rates. This
      review summarizes the state-of-the-art computational methods for the discovery of
      modulators and bitopic ligands. The challenges and opportunities for future drug
      discovery are also discussed. 

PMID- 25940086
TI  - Kelch Repeat and BTB Domain Containing Protein 5 (Kbtbd5) Regulates Skeletal
      Muscle Myogenesis through the E2F1-DP1 Complex.
AB  - We have previously isolated a muscle-specific Kelch gene, Kelch repeat and BTB
      domain containing protein 5 (Kbtbd5)/Kelch-like protein 40 (Klhl40). In this
      report, we identified DP1 as a direct interacting factor for Kbtbd5 using a yeast
      two-hybrid screen and in vitro binding assays. Our studies demonstrate that
      Kbtbd5 interacts and regulates the cytoplasmic localization of DP1. GST pulldown
      assays demonstrate that the dimerization domain of DP1 interacts with all three
      of the Kbtbd5 domains. We further show that Kbtbd5 promotes the ubiquitination
      and degradation of DP1, thereby inhibiting E2F1-DP1 activity. To investigate the
      in vivo function of Kbtbd5, we used gene disruption technology and engineered
      Kbtbd5 null mice. Targeted deletion of Kbtbd5 resulted in postnatal lethality.
      Histological studies reveal that the Kbtbd5 null mice have smaller muscle fibers,
      a disorganized sarcomeric structure, increased extracellular matrix, and
      decreased numbers of mitochondria compared with wild-type controls. RNA
      sequencing and quantitative PCR analyses demonstrate the up-regulation of E2F1
      target apoptotic genes (Bnip3 and p53inp1) in Kbtbd5 null skeletal muscle.
      Consistent with these observations, the cellular apoptosis in Kbtbd5 null mice
      was increased. Breeding of Kbtbd5 null mouse into the E2F1 null background
      rescues the lethal phenotype of the Kbtbd5 null mice but not the growth defect.
      The expression of Bnip3 and p53inp1 in Kbtbd5 mutant skeletal muscle are also
      restored to control levels in the E2F1 null background. In summary, our studies
      demonstrate that Kbtbd5 regulates skeletal muscle myogenesis through the
      regulation of E2F1-DP1 activity. 

PMID- 25940087
TI  - Ganglioside GD3 Enhances Invasiveness of Gliomas by Forming a Complex with
      Platelet-derived Growth Factor Receptor alpha and Yes Kinase.
AB  - There have been a few studies on the ganglioside expression in human glioma
      tissues. However, the role of these gangliosides such as GD3 and GD2 has not been
      well understood. In this study we employed a genetically engineered mouse model
      of glioma to clarify the functions of GD3 in gliomas. Forced expression of
      platelet-derived growth factor B in cultured astrocytes derived from p53
      deficient mice resulted in the expression of GD3 and GD2. GD3-positive astrocytes
      exhibited increased cell growth and invasion activities along with elevated
      phosphorylation of Akt and Yes kinase. By enzyme-mediated activation of radical
      sources reaction and mass spectrometry, we identified PDGF receptor alpha
      (PDGFRalpha) as a GD3-associated molecule. GD3-positive astrocytes showed a
      significant amount of PDGFRalpha in glycolipid-enriched microdomains/rafts
      compared with GD3-negative cells. Src kinase family Yes was co-precipitated with
      PDGFRalpha, and its pivotal role in the increased cell invasion of GD3-positive
      astrocytes was demonstrated by silencing with anti-Yes siRNA. Direct association
      between PDGFRalpha and GD3 was also shown, suggesting that GD3 forms ternary
      complex with PDGFRalpha and Yes. The fact that GD3, PDGFRalpha, and activated Yes
      were colocalized in lamellipodia and the edge of tumors in cultured cells and
      glioma tissues, respectively, suggests that GD3 induced by platelet-derived
      growth factor B enhances PDGF signals in glycolipid-enriched microdomain/rafts,
      leading to the promotion of malignant phenotypes such as cell proliferation and
      invasion in gliomas. 

PMID- 25940088
TI  - Comparative Biochemical and Functional Analysis of Viral and Human Secreted Tumor
      Necrosis Factor (TNF) Decoy Receptors.
AB  - The blockade of tumor necrosis factor (TNF) by etanercept, a soluble version of
      the human TNF receptor 2 (hTNFR2), is a well established strategy to inhibit
      adverse TNF-mediated inflammatory responses in the clinic. A similar strategy is
      employed by poxviruses, encoding four viral TNF decoy receptor homologues
      (vTNFRs) named cytokine response modifier B (CrmB), CrmC, CrmD, and CrmE. These
      vTNFRs are differentially expressed by poxviral species, suggesting distinct
      immunomodulatory properties. Whereas the human variola virus and mouse ectromelia
      virus encode one vTNFR, the broad host range cowpox virus encodes all vTNFRs. We
      report the first comprehensive study of the functional and binding properties of
      these four vTNFRs, providing an explanation for their expression profile among
      different poxviruses. In addition, the vTNFRs activities were compared with the
      hTNFR2 used in the clinic. Interestingly, CrmB from variola virus, the causative
      agent of smallpox, is the most potent TNFR of those tested here including hTNFR2.
      Furthermore, we demonstrate a new immunomodulatory activity of vTNFRs, showing
      that CrmB and CrmD also inhibit the activity of lymphotoxin beta. Similarly, we
      report for the first time that the hTNFR2 blocks the biological activity of
      lymphotoxin beta. The characterization of vTNFRs optimized during virus-host
      evolution to modulate the host immune response provides relevant information
      about their potential role in pathogenesis and may be used to improve anti
      inflammatory therapies based on soluble decoy TNFRs. 

PMID- 25940089
TI  - The Function of Embryonic Stem Cell-expressed RAS (E-RAS), a Unique RAS Family
      Member, Correlates with Its Additional Motifs and Its Structural Properties.
AB  - E-RAS is a member of the RAS family specifically expressed in embryonic stem
      cells, gastric tumors, and hepatic stellate cells. Unlike classical RAS isoforms
      (H-, N-, and K-RAS4B), E-RAS has, in addition to striking and remarkable sequence
      deviations, an extended 38-amino acid-long unique N-terminal region with still
      unknown functions. We investigated the molecular mechanism of E-RAS regulation
      and function with respect to its sequence and structural features. We found that
      N-terminal extension of E-RAS is important for E-RAS signaling activity. E-RAS
      protein most remarkably revealed a different mode of effector interaction as
      compared with H-RAS, which correlates with deviations in the effector-binding
      site of E-RAS. Of all these residues, tryptophan 79 (arginine 41 in H-RAS), in
      the interswitch region, modulates the effector selectivity of RAS proteins from H
      RAS to E-RAS features. 

PMID- 25940090
TI  - Parvulin 17-catalyzed Tubulin Polymerization Is Regulated by Calmodulin in a
      Calcium-dependent Manner.
AB  - Recently we have shown that the peptidyl-prolyl cis/trans isomerase parvulin 17
      (Par17) interacts with tubulin in a GTP-dependent manner, thereby promoting the
      formation of microtubules. Microtubule assembly is regulated by Ca(2+)-loaded
      calmodulin (Ca(2+)/CaM) both in the intact cell and under in vitro conditions via
      direct interaction with microtubule-associated proteins. Here we provide the
      first evidence that Ca(2+)/CaM interacts also with Par17 in a physiologically
      relevant way, thus preventing Par17-promoted microtubule assembly. In contrast,
      parvulin 14 (Par14), which lacks only the first 25 N-terminal residues of the
      Par17 sequence, does not interact with Ca(2+)/CaM, indicating that this
      interaction is exclusive for Par17. Pulldown experiments and chemical shift
      perturbation analysis with (15)N-labeled Par17 furthermore confirmed that
      calmodulin (CaM) interacts in a Ca(2+)-dependent manner with the Par17 N
      terminus. The reverse experiment with (15)N-labeled Ca(2+)/CaM demonstrated that
      the N-terminal Par17 segment binds to both CaM lobes simultaneously, indicating
      that Ca(2+)/CaM undergoes a conformational change to form a binding channel
      between its two lobes, apparently similar to the structure of the CaM-smMLCK(796
      815) complex. In vitro tubulin polymerization assays furthermore showed that
      Ca(2+)/CaM completely suppresses Par17-promoted microtubule assembly. The results
      imply that Ca(2+)/CaM binding to the N-terminal segment of Par17 causes steric
      hindrance of the Par17 active site, thus interfering with the Par17/tubulin
      interaction. This Ca(2+)/CaM-mediated control of Par17-assisted microtubule
      assembly may provide a mechanism that couples Ca(2+) signaling with microtubule
      function. 

PMID- 25940092
TI  - Histone deacetylase 3 expression correlates with vasculogenic mimicry through the
      phosphoinositide3-kinase / ERK-MMP-laminin5gamma2 signaling pathway.
AB  - Vasculogenic mimicry (VM) refers to the process by which highly aggressive tumor
      cells mimic endothelial cells to form vessel-like structures that aid in
      supplying enough nutrients to rapidly growing tumors. Histone deacetylases
      (HDACs) regulate the expression and activity of numerous molecules involved in
      cancer initiation and progression. Notably, HDAC3 is overexpressed in the
      majority of carcinomas. However, thus far, no data are available to support the
      role of HDAC3 in VM. In this study, we subjected glioma specimens to
      immunohistochemical and histochemical double-staining methods and found that VM
      and HDAC3 expression were related to the pathological grade of gliomas. The
      presence of VM correlated with HDAC3 expression in glioma tissues. The formation
      of tubular structures, as determined by the tube formation assay to evaluate VM,
      was impaired in U87MG cells when transfected by siRNA or treated with an HDAC3
      inhibitor. Importantly, the expression of VM-related molecules such as MMP-2/14
      and laminin5gamma2 was also affected when HDAC3 expression was altered.
      Furthermore, U87MG cells were treated with a phosphoinositide 3-kinase (PI3K)
      inhibitor or/and ERK inhibitor and found that the PI3K and ERK signaling pathways
      play key roles in VM; whereas, in VM, the two signaling pathways did not act
      upstream or downstream from each other. Taken together, our findings showed that
      HDAC3 contributed to VM in gliomas, possibly through the PI3K/ERK-MMPs
      laminin5gamma2 signaling pathway, which could potentially be a novel therapeutic
      target for gliomas. 

PMID- 25940094
TI  - Enhanced microgas chromatography using correlation techniques for continuous
      indoor pollutant detection.
AB  - We present for the first time a proof-of-concept system implementing the
      stochastic injection techniques within a silicon-based microgas chromatograph
      (MUGC) which differs from standard laboratory chromatographs by its small size,
      shorter column and corresponding elution times, and potential low cost when batch
      manufactured in high volumes. We demonstrate that stochastic injection techniques
      can enable the continuous detection of pollutants or toxic gases, with high
      temporal resolution (5 s) and order-of-magnitude improvements in limit of
      detection compared to a standard single-injection technique, thus greatly
      improving performance of air quality monitoring devices. Since micro-GC systems
      have the potential to 1 day become ubiquitous in indoor environments, such
      stochastic injection techniques could enable faster detection of toxic compounds
      at lower concentrations in both industrial and residential settings. 

PMID- 25940093
TI  - Temporal perception deficits in schizophrenia: integration is the problem, not
      deployment of attentions.
AB  - Patients with schizophrenia are known to have impairments in sensory processing.
      In order to understand the specific temporal perception deficits of
      schizophrenia, we investigated and determined to what extent impairments in
      temporal integration can be dissociated from attention deployment using
      Attentional Blink (AB). Our findings showed that there was no evident deficit in
      the deployment of attention in patients with schizophrenia. However, patients
      showed an increased temporal integration deficit within a hundred-millisecond
      timescale. The degree of such integration dysfunction was correlated with the
      clinical manifestations of schizophrenia. There was no difference between
      individuals with/without schizotypal personality disorder in temporal
      integration. Differently from previous studies using the AB, we did not find a
      significant impairment in deployment of attention in schizophrenia. Instead, we
      used both theoretical and empirical approaches to show that previous findings
      (using the suppression ratio to correct for the baseline difference) produced a
      systematic exaggeration of the attention deficits. Instead, we modulated the
      perceptual difficulty of the task to bring the baseline levels of target
      detection between the groups into closer alignment. We found that the integration
      dysfunction rather than deployment of attention is clinically relevant, and thus
      should be an additional focus of research in schizophrenia. 

PMID- 25940095
TI  - Tuning the acoustic frequency of a gold nanodisk through its adhesion layer.
AB  - To fabricate robust metallic nanostructures with top-down patterning methods such
      as electron-beam lithography, an initial nanometer-scale layer of a second metal
      is deposited to promote adhesion of the metal of interest. However, how this
      nanoscale layer affects the mechanical properties of the nanostructure and how
      adhesion layer thickness controls the binding strength to the substrate are still
      open questions. Here we use ultrafast laser pulses to impulsively launch acoustic
      phonons in single gold nanodisks with variable titanium layer thicknesses, and
      observe an increase in phonon frequencies as a thicker adhesion layer facilitates
      stronger binding to the glass substrate. In addition to an all-optical
      interrogation of nanoscale mechanical properties, our results show that the
      adhesion layer can be used to controllably modify the acoustic phonon modes of a
      gold nanodisk. This direct coupling between optically excited plasmon modes and
      phonon modes can be exploited for a variety of emerging optomechanical
      applications. 

PMID- 25940091
TI  - La-related Protein 1 (LARP1) Represses Terminal Oligopyrimidine (TOP) mRNA
      Translation Downstream of mTOR Complex 1 (mTORC1).
AB  - The mammalian target of rapamycin complex 1 (mTORC1) is a critical regulator of
      protein synthesis. The best studied targets of mTORC1 in translation are the
      eukaryotic initiation factor-binding protein 1 (4E-BP1) and ribosomal protein S6
      kinase 1 (S6K1). In this study, we identify the La-related protein 1 (LARP1) as a
      key novel target of mTORC1 with a fundamental role in terminal oligopyrimidine
      (TOP) mRNA translation. Recent genome-wide studies indicate that TOP and TOP-like
      mRNAs compose a large portion of the mTORC1 translatome, but the mechanism by
      which mTORC1 controls TOP mRNA translation is incompletely understood. Here, we
      report that LARP1 functions as a key repressor of TOP mRNA translation downstream
      of mTORC1. Our data show the following: (i) LARP1 associates with mTORC1 via
      RAPTOR; (ii) LARP1 interacts with TOP mRNAs in an mTORC1-dependent manner; (iii)
      LARP1 binds the 5'TOP motif to repress TOP mRNA translation; and (iv) LARP1
      competes with the eukaryotic initiation factor (eIF) 4G for TOP mRNA binding.
      Importantly, from a drug resistance standpoint, our data also show that reducing
      LARP1 protein levels by RNA interference attenuates the inhibitory effect of
      rapamycin, Torin1, and amino acid deprivation on TOP mRNA translation.
      Collectively, our findings demonstrate that LARP1 functions as an important
      repressor of TOP mRNA translation downstream of mTORC1. 

PMID- 25940096
TI  - NKp46 regulates the production of serine proteases and IL-22 in human mast cells
      in urticaria pigmentosa.
AB  - NKp46 (natural cytotoxic receptor 1/CD335) is expressed on natural killer cells
      and Th2-type innate lymphocytes. However, NKp46 expression in human mast cells
      has not yet been reported. Here, we explored the expression of, and possible role
      played by, NKp46 in such cells. NKp46 protein was expressed in human mast cells
      in urticaria pigmentosa principally of the tryptase-positive/chymase-negative
      type (MCT), but not in human non-neoplastic skin mast cells of the tryptase
      positive/chymase-positive (MCTC) type. NKp46 expression was also evident in the
      human neoplastic mast cell line HMC1.2. NKp46 knockdown changed the phenotype of
      this cell line from MCT to MCTC and downregulated GrB production, but did not
      influence IL-22 production. An agonistic anti-NKp46 antibody upregulated
      production of GrB and IL-22, but did not change the MCT-like phenotype of HMC1.2
      cells. NKp46 was thus involved in the production of serine proteases and IL-22 in
      human mast cells. 

PMID- 25940097
TI  - Transcranial direct current stimulation to the parietal cortex in hemispatial
      neglect: A feasibility study.
AB  - OBJECTIVES: Prior research suggests that dampening neural activity of the intact,
      presumably overactive hemisphere, combined with increasing neural activity in the
      damaged hemisphere, might restore cortical interhemispheric balance and reduce
      neglect. In the present study we repeatedly applied a relatively new technique,
      transcranial direct current stimulation (tDCS), to the posterior parietal cortex
      to modulate spontaneous neural activity levels in a polarity dependent fashion to
      find evidence for improvements in severe hemispatial neglect in chronic patients.
      METHODS: Eighty-nine patients were initially identified from our databases as
      having neglect, after thoroughly screening databases, consulting medical
      practitioners and baseline testing, only five met our inclusion criteria and
      agreed to participate. Sixty-five patients were excluded as they did not meet
      safety criteria for tDCS (epilepsy, metal implants), suffered from other medical
      conditions (i.e., heart disease, epilepsy, current psychiatric disorder) or
      displayed only mild neglect at baseline testing. Five patients with severe
      chronic hemispatial neglect were enrolled in a double-blind, placebo-controlled
      treatment program. TDCS or placebo was applied for 20 minutes over the left
      (cathodal) and right (anodal) posterior parietal cortex at an intensity of 2 mA
      on five consecutive days. Treatment conditions were separated by a four week wash
      out period. Baseline corrected change in performance on the conventional subtests
      of the Behavioral Inattention Test (BIT) was our primary endpoint. RESULTS: No
      treatment-related effects were observed for the BIT change scores and performance
      on individual subtests. Moreover, patients' performance somewhat improved only
      during the stimulation period (day one vs day five, irrespective of whether it
      was placebo or tDCS), but not thirty days later, indicating a practice effect.
      DISCUSSION: The present study does not provide evidence that tDCS to the
      posterior parietal cortex improves chronic hemispatial neglect. As a result of in
      and exclusion health and safety criteria the majority of patients were excluded,
      which indicates that performing large randomized controlled trials is not
      feasible in chronic neglect patients.

PMID- 25940099
TI  - Developmental changes in the neural influence of sublexical information on
      semantic processing.
AB  - Functional magnetic resonance imaging (fMRI) was used to examine the
      developmental changes in a group of normally developing children (aged 8-12) and
      adolescents (aged 13-16) during semantic processing. We manipulated association
      strength (i.e. a global reading unit) and semantic radical (i.e. a local reading
      unit) to explore the interaction of lexical and sublexical semantic information
      in making semantic judgments. In the semantic judgment task, two types of stimuli
      were used: visually-similar (i.e. shared a semantic radical) versus visually
      dissimilar (i.e. did not share a semantic radical) character pairs. Participants
      were asked to indicate if two Chinese characters, arranged according to
      association strength, were related in meaning. The results showed greater
      developmental increases in activation in left angular gyrus (BA 39) in the
      visually-similar compared to the visually-dissimilar pairs for the strong
      association. There were also greater age-related increases in angular gyrus for
      the strong compared to weak association in the visually-similar pairs. Both of
      these results suggest that shared semantics at the sublexical level facilitates
      the integration of overlapping features at the lexical level in older children.
      In addition, there was a larger developmental increase in left posterior middle
      temporal gyrus (BA 21) for the weak compared to strong association in the
      visually-dissimilar pairs, suggesting conflicting sublexical information placed
      greater demands on access to lexical representations in the older children. All
      together, these results suggest that older children are more sensitive to
      sublexical information when processing lexical representations. 

PMID- 25940100
TI  - A mussel-inspired adhesive with stronger bonding strength under underwater
      conditions than under dry conditions.
AB  - A mussel-inspired adhesive based on a polyvinylpyrrolidone (PVP) backbone shows a
      much higher bonding strength under underwater/seawater conditions than under dry
      conditions. We reasoned that besides catechol moieties, the structure and
      properties of the backbone also play an important role in the realization of
      strong underwater bonding. 

PMID- 25940098
TI  - Intraparietal regions play a material general role in working memory: Evidence
      supporting an internal attentional role.
AB  - Determining the role of intraparietal sulcus (IPS) regions in working memory (WM)
      remains a topic of considerable interest and lack of clarity. One group of
      hypotheses, the internal attention view, proposes that the IPS plays a material
      general role in maintaining information in WM. An alternative viewpoint, the pure
      storage account, proposes that the IPS in each hemisphere maintains material
      specific (e.g., left--phonological; right--visuospatial) information. Yet,
      adjudication between competing theoretical perspectives is complicated by
      divergent findings from different methodologies and their use of different
      paradigms, perhaps most notably between functional magnetic resonance imaging
      (fMRI) and electroencephalography (EEG). For example, fMRI studies typically use
      full field stimulus presentations and report bilateral IPS activation, whereas
      EEG studies direct attention to a single hemifield and report a contralateral
      bias in both hemispheres. Here, we addressed this question by applying a regions
      of-interest fMRI approach to elucidate IPS contributions to WM. Importantly, we
      manipulated stimulus type (verbal, visuospatial) and the cued hemifield to assess
      the degree to which IPS activations reflect stimulus specific or stimulus general
      processing consistent with the pure storage or internal attention hypotheses.
      These data revealed significant contralateral bias along regions IPS0-5
      regardless of stimulus type. Also present was a weaker stimulus-based bias
      apparent in stronger left lateralized activations for verbal stimuli and stronger
      right lateralized activations for visuospatial stimuli. However, there was no
      consistent stimulus-based lateralization of activity. Thus, despite the
      observation of stimulus-based modulation of spatial lateralization this pattern
      was bilateral. As such, although it is quantitatively underspecified, our results
      are overall more consistent with an internal attention view that the IPS plays a
      material general role in refreshing the contents of WM.

PMID- 25940101
TI  - Pleural-based neuroblastoma-like schwannoma: a case report with cytologic
      findings and review of literature.
AB  - We report a rare case of a 45-year-old African American woman with Neuroblastoma
      like Schwannoma (Neurilemmoma) occurring in the posterior mediastinum as a
      pleural-based mass noted on computed tomography (CT) scan. A CT-guided core
      biopsy of the mass was performed and core biopsy imprints were prepared during
      the procedure. A Diff-Quik stain was performed for on-site evaluation of specimen
      adequacy. The hematoxylin and eosin (H&E) staining was evaluated subsequently.
      Immunohistochemistry panels were applied to the same specimen. The cytologic
      findings of the core biopsy imprints showed hypercellular smears with a
      predominance of small cells with atypical features including hyperchromatic,
      round nuclei and occasional nucleoli. Neurocytic rosettes were particularly
      appreciated on H&E stain. The immunohistochemical results exhibited strong and
      diffuse immunoreactivity for S-100 and vimentin. This case enriches the
      cytopathology literature by providing awareness of this tumor presenting as a
      posterior mediastinal mass.

PMID- 25940102
TI  - Adding Amorphous Content to Highly Crystalline Polymer Nanowire Solar Cells
      Increases Performance.
AB  - Polymer solar cells are fabricated with systematic variation of the phase purity.
      Photovoltaic tests demonstrate that devices with ca. 10% of mixed phases
      outperform pure-phase devices. Photophysical studies reveal the effects of mixed
      phase on charge generation and recombination. These results show a promising
      strategy for the optimization of organic electronic materials. 

PMID- 25940103
TI  - Photodynamic therapy simplified: nonprepared, moderate-grade actinic keratosis
      lesions respond equally well to 5-aminolaevulinic acid patch photodynamic therapy
      as do mild lesions.

PMID- 25940104
TI  - Methylphenidate improves the quality of life of children and adolescents with
      ADHD and difficult-to-treat epilepsies.
AB  - OBJECTIVE: Comorbidity between difficult-to-treat epilepsies and ADHD is frequent
      and impacts negatively on quality of life. The commonly held (yet poorly
      substantiated) view that stimulants may worsen seizure control has prevented
      studies from evaluating the impact of such treatment in this population. Our aim
      was to study the effect of methylphenidate on the quality of life of children and
      adolescents with difficult-to-treat epilepsies and comorbid ADHD. METHODS: The
      study was an open-label, noncontrolled trial with intention-to-treat analysis
      following 30 patients for 6months. Subjects received methylphenidate following
      3months of baseline, during which antiepileptic drugs (AEDs) were adjusted and
      epilepsy, ADHD, and quality-of-life variables were assessed. Multivariate
      regression analysis identified the main variables correlated with outcome.
      RESULTS: Only one patient withdrew because of seizure worsening. Following
      methylphenidate introduction, doses were titrated up to 0.40-0.50mg/kg/day. A
      marked improvement in quality-of-life scores and a significant reduction in
      seizure frequency and severity were observed. Female sex, reduction of core ADHD
      symptoms, and tolerability to adequate doses of methylphenidate were
      significantly associated with improved quality-of-life scores. CONCLUSION: These
      preliminary data suggest that methylphenidate treatment is safe and effective in
      patients with ADHD and difficult-to-treat epilepsies, positively impacting on
      quality-of-life scores.

PMID- 25940105
TI  - The Visual Word Form Area remains in the dominant hemisphere for language in late
      onset left occipital lobe epilepsies: A postsurgery analysis of two cases.
AB  - Automatic recognition of words from letter strings is a critical processing step
      in reading that is lateralized to the left-hemisphere middle fusiform gyrus in
      the so-called Visual Word Form Area (VWFA). Surgical lesions in this location can
      lead to irreversible alexia. Very early left hemispheric lesions can lead to
      transfer of the VWFA to the nondominant hemisphere, but it is currently unknown
      if this capability is preserved in epilepsies developing after reading
      acquisition. In this study, we aimed to determine the lateralization of the VWFA
      in late-onset left inferior occipital lobe epilepsies and also the effect of
      surgical disconnection from the adjacent secondary visual areas. Two patients
      with focal epilepsies with onset near the VWFA underwent to surgery for epilepsy,
      with sparing of this area. Neuropsychology evaluations were performed before and
      after surgery, as well as quantitative evaluation of the speed of word reading.
      Comparison of the surgical localization of the lesion, with the BOLD activation
      associated with the contrast of words-strings, was performed, as well as a study
      of the associated main white fiber pathways using diffusion-weighted imaging.
      Neither of the patients developed alexia after surgery (similar word reading
      speed before and after surgery) despite the fact that the inferior occipital
      surgical lesions reached the neighborhood (less than 1cm) of the VWFA. Surgeries
      partly disconnected the VWFA from left secondary visual areas, suggesting that
      pathways connecting to the posterior visual ventral stream were severely affected
      but did not induce alexia. The anterior and superior limits of the resection
      suggest that the critical connection between the VWFA and the Wernicke's Angular
      Gyrus cortex was not affected, which is supported by the detection of this tract
      with probabilistic tractography. Left occipital lobe epilepsies developing after
      reading acquisition did not produce atypical localizations of the VWFA, even with
      foci in the close neighborhood. Surgery for occipital lobe epilepsy should take
      this into consideration, as well as the fact that disconnection from the left
      secondary visual areas may not produce alexia. 

PMID- 25940106
TI  - Ultrasound stimulation inhibits recurrent seizures and improves behavioral
      outcome in an experimental model of mesial temporal lobe epilepsy.
AB  - Current therapies for epilepsy consist mostly of pharmacological agents or
      invasive surgery. Recently, ultrasound (US) stimulation has been considered a
      promising tool for the noninvasive treatment of brain diseases, including
      epilepsy. However, in temporal lobe epilepsy (TLE), a common form of epilepsy,
      neurophysiological and functional outcomes following US stimulation are not well
      defined. To address this, we developed a paradigm of transcranial pulsed US
      stimulation to efficiently suppress seizure activity in the initial/acute period
      in a kainate (KA)-induced mouse model of mesial TLE. Pulsed US stimulation
      inhibited acute seizure activity and either delayed the onset of or suppressed
      status epilepticus (SE). Kainate-treated mice that had received US stimulation in
      the initial period exhibited fewer spontaneous recurrent seizures (SRSs) and
      improved performance in behavioral tasks assessing sociability and depression in
      the chronic period of epilepsy. Our results demonstrate that US stimulation in
      the acute period of epilepsy can inhibit SRSs and improve behavioral outcomes in
      a mouse model of mesial TLE. The present study suggests that noninvasive
      transcranial pulsed US stimulation may be feasible as an adjuvant therapy in
      patients with epilepsy. This article is part of a Special Issue entitled "Status
      Epilepticus". 

PMID- 25940107
TI  - Clobazam is equally safe and efficacious for seizures associated with Lennox
      Gastaut syndrome across different age groups: Post hoc analyses of short- and
      long-term clinical trial results.
AB  - The peak age at onset of Lennox-Gastaut syndrome (LGS) is between 3 and 5years.
      Patients with LGS frequently experience multiple types of treatment-refractory
      seizures and require lifelong therapy with several antiepileptic drugs. Here,
      post hoc analyses of clinical trials (phase III trial OV-1012 and open-label
      extension trial OV-1004) provide short- and long-term efficacy and safety data of
      adjunctive clobazam in patients with LGS stratified by age at baseline (>=2 to
      <12years, >=12 to <17years, and >=17years). In OV-1012, 301 patients were
      screened, 238 were randomized, 217 comprised the modified intention-to-treat
      population, and 177 completed the study. A total of 267/306 patients (61 of 68
      from phase II trial OV-1002 and 206 of 238 from phase III trial OV-1012) entered
      the open-label extension trial. Demographics and clinical characteristics were
      similar between different age groups in OV-1012 and OV-1004. No differences in
      efficacy or adverse events were observed across age groups in OV-1012 and OV
      1004. The results of these post hoc analyses show that adjunctive clobazam over
      the short and longterm was similarly effective and well-tolerated in both
      pediatric and adult patients with LGS. 

PMID- 25940108
TI  - A CT60G>A polymorphism in the CTLA-4 gene of the recipient may confer
      susceptibility to acute graft versus host disease after allogeneic hematopoietic
      stem cell transplantation.
AB  - T cell activation plays a crucial role in the development of acute graft versus
      host disease (aGvHD). Cytotoxic T cell antigen-4 (CTLA-4) is a co-inhibitory
      molecule that negatively regulates T cell activation, differentiation, and
      proliferation. Single-nucleotide polymorphisms (SNPs) in CTLA-4 gene may affect
      its function. Inconsistent observations have been reported regarding the
      associations of CTLA-4 SNPs with complications after hematopoietic stem cell
      transplantation (HSCT). Moreover, the majority of the observations were focused
      on the donors' SNPs. Recently, a few studies have shown that recipients' genetic
      variations in the CTLA-4 gene might influence HSCT results. The aim of our study
      was to determine the influence of the CTLA-4 gene polymorphisms of the donors and
      the recipients on the outcome of HSCT. Altogether, 312 donor-recipient pairs were
      genotyped for the CTLA-4c.49A>G (rs231775) and CT60G>A (rs3087243) SNPs using the
      TaqMan(r)SNP Genotyping Assays. In this study, it was shown that the recipients'
      CT60G>A[GG] genotype, the myeloablative conditioning regimen, and HSCT from an
      unrelated donor were independent aGvHD risk factors (odds ratio (OR) 2.63, 95%
      confidence intervals (95% CI) 1.45-4.59, p = 0.001; OR 2.68, 95% CI 1.65-4.07, p
      = 0.00003; and OR 1.87, 95 % CI 1.02-3.24, p = 0.04, respectively). Moreover,
      haplotype analysis revealed that possessing allele A in both of the SNPs
      decreased the risk of aGvHD approximately 1.5-fold (RR 0.69, p = 0.008). Our data
      suggest that the CT60G>A[GG] genotype in the recipient has an impact on aGvHD
      development, especially in patients receiving transplants from unrelated donors
      together with the myeloablative conditioning regimen.

PMID- 25940109
TI  - On the genetics of the Silk Route: association analysis of HLA, IL10, and IL23R
      IL12RB2 regions with Behcet's disease in an Iranian population.
AB  - Despite that the association of Behcet's disease (BD) with the HLA-B5 was first
      established in the 1970s, a number of recent genome-wide association studies have
      both confirmed and furthered this association--in various populations--to
      individual SNPs both inside and outside the HLA. The former include HLA-B, MICA,
      and HLA-A, while the latter encompass IL10 and IL23R-IL12RB2 regions. The present
      study examined whether some of these SNPs could be replicated in an Iranian
      population, where the prevalence of disease is amply documented. Eight SNPs were
      selected and tested in 552 patients and 417 controls. These were rs7539328,
      rs12119179, rs1495965, rs1518111, and rs1800871 in IL10 and IL23R-IL12RB2 regions
      and rs114854070, rs12525170, and rs76546355 (formerly rs116799036) in the HLA
      locus. The well-known BD-associated genes HLA-B and MICA were independently
      genotyped. Although we were not able to formally replicate the association with
      IL10 and IL23R-IL12RB2, we do report that BD in Iran is strongly associated with
      HLA-B*51, MICA-A6, and the three HLA-linked SNPs (odds ratio (OR) = 3.38, P =
      6.21 * 10(-14); OR = 2.08, P = 1.58 * 10(-13); and OR = 1.67-4.05, P = 1.45 * 10(
      04) to 4.79 * 10(-34), respectively). Our data further indicate that the robust
      HLA-B/MICA association may be explained by a single variant (rs76546355) between
      the two genes. Overall, these data contribute to a better appraisal of the
      intriguing linkage between BD and the ancient Silk Route, spanning from the
      Mediterranean shores to Japan.

PMID- 25940110
TI  - A water-stable lanthanide-organic framework as a recyclable luminescent probe for
      detecting pollutant phosphorus anions.
AB  - A novel 3D Eu-BTB framework () containing three types of 1D channels was
      synthesized and structurally characterized. Compound exhibits high
      thermostability and water stability with the pH range from 2 to 12. Additionally,
      the luminescence explorations revealed that can sensitively and selectively
      detect pollutant PO4(3-) among various colourless anions. More importantly,
      represents the first example of regenerable MOF-based luminescent probes for
      detecting PO4(3-). 

PMID- 25940111
TI  - Multistage three-dimensional UTE lung imaging by image-based self-gating.
AB  - PURPOSE: To combine image-based self-gating (img-SG) with ultrashort echo time
      (UTE) three-dimensional (3D) acquisition for multistage lung imaging during free
      breathing. METHODS: Three k-space ordering schemes (modified spiral pattern,
      quasirandom numbers and multidimensional Golden Angle) providing uniform coverage
      of k-space were investigated for providing low-resolution sliding-window images
      for image-based respiratory self-gating. The performance of the proposed
      techniques were compared with the conventional spiral pattern and standard DC
      based self-gated methods in volunteers during free breathing. RESULTS: Navigator
      like respiratory signals were successfully extracted from the sliding-window data
      by monitoring the lung-liver interface displacement. A temporal resolution of 588
      ms was adequate to retrieve gating signals from the lung-liver interface. Images
      reconstructed with the img-SG technique showed significantly better sharpness and
      apparent diaphragm excursion than any of the DC-SG methods. Direct comparison of
      the three implemented ordering schemes did not demonstrate any clear superiority
      of one with respect to the others. CONCLUSION: Image-based respiratory self
      gating in UTE 3D lung images allows successful retrospective respiratory gating,
      also enabling reconstruction of intermediate respiratory stages.

PMID- 25940112
TI  - Exposure to radiation therapy is associated with female reproductive health among
      childhood cancer survivors: a meta-analysis study.
AB  - BACKGROUND AND AIMS: Many epidemiological studies have revealed a positive
      correlation between medical radiation exposure and the reproductive health in
      female childhood cancer survivors. However, because of variations in the samples
      size, such studies showed partly inconsistent conclusions. The aim of this meta
      analysis was to clarify the association between radiotherapy and the risk of
      reproductive health impairment for female who survived from childhood cancer.
      METHODS: Fourteen cohort studies involving childhood radiotherapy were selected
      as the exposure of interest and the impaired reproductive health condition during
      the childbearing age as the outcome. Among meta-analysis of observational studies
      found in Pubmed and Embase from 1900 to 2014, we evaluated those relevant
      observational studies which surveyed the association of medical radiation and
      reproductive health in female childhood cancer survivors. Review Manager 5.2 and
      STATA 12.0 software were used to perform the meta-analysis. Study-specific
      estimations for each outcome were combined into a pooled relative risk (RR) with
      95% confidence interval (CI) by a meta-analytic approach. RESULTS: Based on a
      random-effects meta-analysis, significant association between infertility (RR =
      1.28, 95% CI = 1.16-1.42), acute ovarian failure (AOF) (RR = 9.51, 95% CI = 5.03
      17.96), low level of anti mullerian hormone (AMH) (<1 ng/mL) (RR = 14.79, 95% CI
      = 3.36-66.64), stillbirth (RR = 1.19, 95% CI = 1.02-1.39) and low birth weight
      (RR = 2.22, 95% CI = 1.55-3.17) were identified. Conversely, no significant
      results were found in abortion and congenital malformations. CONCLUSIONS: To the
      best of our knowledge, this is the first meta-analysis assessing the effect of
      medical radiation on female childhood cancer survivors' reproductive capability
      and pregnancy outcomes. Although there were some limitations, our meta-analysis
      further supported that radiotherapy was a risk factor for reproductive health
      problems of female who survived from childhood cancer.

PMID- 25940113
TI  - Between Tradition and Modernity: Marriage Dynamics in Kyrgyzstan.
AB  - The demographic literature on union formation in post-communist Europe typically
      documents retreat from marriage and increase in cohabitation. However,
      sociological and anthropological studies of post-Soviet Central Asia often point
      to a resurgence of various traditional norms and practices, including those
      surrounding marriage, that were suppressed under Soviet rule. We engage these two
      perspectives on union formation by analyzing transition to first marriage in
      Kyrgyzstan both before and after the collapse of the USSR. We use uniquely
      detailed marriage histories from a nationally representative survey conducted in
      the period 2011-2012 to examine the dynamics of traditional marital practices
      among that country's two main ethnic groups-Kyrgyz and Uzbeks-focusing on trends
      in arranged marriages and in marriages involving bride kidnapping. The analysis
      reveals instructive ethnic and period differences but also indicates an overall
      decline in the risks of both types of traditional marriage practices in the post
      Soviet era. In fact, although the decline has characterized all marriage types,
      it was more substantial for traditional marriages. We interpret these trends as
      evidence of continuing modernization of nuptiality behavior in the region. 

PMID- 25940114
TI  - Single Benzene Green Fluorophore: Solid-State Emissive, Water-Soluble, and
      Solvent- and pH-Independent Fluorescence with Large Stokes Shifts.
AB  - Benzene is the simplest aromatic hydrocarbon with a six-membered ring. It is one
      of the most basic structural units for the construction of pi conjugated systems,
      which are widely used as fluorescent dyes and other luminescent materials for
      imaging applications and displays because of their enhanced spectroscopic signal.
      Presented herein is 2,5-bis(methylsulfonyl)-1,4-diaminobenzene as a novel
      architecture for green fluorophores, established based on an effective push-pull
      system supported by intramolecular hydrogen bonding. This compound demonstrates
      high fluorescence emission and photostability and is solid-state emissive, water
      soluble, and solvent- and pH-independent with quantum yields of Phi=0.67 and
      Stokes shift of 140 nm (in water). This architecture is a significant departure
      from conventional extended pi-conjugated systems based on a flat and rigid
      molecular design and provides a minimum requirement for green fluorophores
      comprising a single benzene ring.

PMID- 25940115
TI  - Socio-demographic and behavioural characteristics associated with HSV-2 sero
      prevalence in high risk women in KwaZulu-Natal.
AB  - BACKGROUND: The World Health Organization estimates that 536 million people aged
      15-49 are infected with Herpes simplex virus type 2 (HSV-2), the causative agent
      of genital herpes. The aim of this study was to investigate the role of
      behavioral and demographic factors that contribute to the high HSV-2 sero
      prevalence among women participating in a HIV prevention trial. The Methods for
      Improving Reproductive Health in Africa (MIRA) study assessed the effectiveness
      the latex diaphragm and lubricant gel on HIV prevention among women in South
      Africa and Zimbabwe. At screening an interviewer administered questionnaire on
      demographics and sexual behaviour was obtained. HSV-2 serum antibodies were
      detected using HerpeSelectTM ELISA IgG. Statistical analysis was performed using
      STATA release 12.0. This study was registered with ClinicalTrials.gov,number
      NCT00121459 on the 28th February 2007. FINDINGS: Of the 3 472 women screened at
      the Durban research sites 2 218 (73%) had a prevalent HSV-2 infection and 1431
      (41%) of the women were also co-infected with HIV. In the multivariate analyses,
      older women (adjusted odds ratio) [aOR]: 3.49, 95% CI: (2.71,4.49) for >35 years
      and aOR: 1.82, 95% CI: 1.49, 2.22 for 25-34 years compared with <25 years, p <
      0.001 for both comparisons were more likely to be HSV-2 sero-positive. Low level
      of education (OR: 1.26 95% CI: 1.03, 1.53), having >1 life-time sexual partners
      (OR: 2.48, 95% CI: 1.92, 3.20), parity >1 (OR: 1.95 95% CI: 1.92, 3.20) and being
      HIV positive (OR: 6.31, 95% CI: 5.06, 7.88) were significantly associated with
      HSV-2 infection. CONCLUSION: The high sero-prevalence of HSV-2 in the studied
      population is of great public health importance since this high risk population
      could act as a reservoir for future infections particularly HIV transmission.

PMID- 25940116
TI  - From the Editor's Desk.

PMID- 25940117
TI  - Association of Helicobacter pylori infection with the metabolic syndrome among
      HIV-infected black Africans receiving highly active antiretroviral therapy.
AB  - INTRODUCTION: The metabolic syndrome (MetS) is common in human immune deficiency
      virus (HIV)-infected individuals receiving highly active antiretroviral therapy
      (HAART). Immune deficiencies caused by HIV give rise to numerous opportunistic
      gastrointestinal pathogens such as Helicobacter pylori, the commonest cause of
      chronic gastritis. The study sought to determine the relationship between H
      pylori infection and the MetS among HIV-infected clinic attendees. METHODS: This
      cross-sectional study was carried out in a specialised heart clinic in Kinshasa,
      DR Congo. Between January 2004 and December 2008, 116 HIV-infected patients (61
      with MetS and 55 without MetS) who underwent upper gastrointestinal endoscopy for
      dyspeptic symptoms were included in the study following an informed consent.
      Univariate associations were determined by odds ratios (OR), while multivariate
      logistic regression analysis was used to identify factors associated with the
      MetS. RESULTS: H pylori infection (OR = 13.5, 95% CI: 10.3-17.6; p < 0.0001) and
      peripheral obesity (median hip circumference >= 97 cm) (OR = 4.7, 95% CI: 1.2
      18.8; p = 0.029) were identified as MetS-related factors in HIV-infected
      patients. Higher rates of the MetS were associated with increased incidence of
      HIV-related immunocompromise using World Health Organisation (WHO) staging
      criteria. There was a univariate significant difference in the prevalence of the
      MetS between antiretroviral therapy (ART)-naive patients and patients treated by
      means of a first-line HAART regimen of stavudine (d4T), lamivudine (3TC) and
      nevirapine (NVP). However, this difference was not significant in multivariate
      logistic analysis. CONCLUSION: H pylori infection was significantly associated
      with the MetS in HIV-infected patients.

PMID- 25940118
TI  - Knowledge, attitude and behaviour regarding dietary salt intake among medical
      students in Angola.
AB  - BACKGROUND: Levels of salt consumption and its awareness among medical students
      in Angola remain insufficiently studied. This study determined salt intake and
      assessed medical students' knowledge, attitude and behaviour regarding salt
      consumption. METHODS: Were collected 24-hour urine samples from a random sample
      of 123 undergraduate medical students aged 17-43 years who were studying at the
      University of Agostinho Neto in Luanda. Their knowledge, attitude and behaviour
      regarding dietary salt were surveyed. Socio-demographic, clinical and
      anthropometric data were collected. RESULTS: Average salt intake was 14.2 +/- 5.1
      g/day, without significant difference between genders (p = 0.221). In total,
      96.7% consumed over 5 g/day, but only 6.5% of participants were aware of their
      excessive salt intake. The majority knew about salt-related health consequences
      and 45.5% reported they controlled their salt intake. CONCLUSIONS: This study
      indicated a high salt intake and inadequate behaviour regarding dietary salt
      consumption among medical students studying at the University of Agostinho Neto.
      This highlights the need for nutritional education to improve their dietary
      habits and future role in counselling.

PMID- 25940119
TI  - Diagnostic disparity and identification of two TNNI3 gene mutations, one novel
      and one arising de novo, in South African patients with restrictive
      cardiomyopathy and focal ventricular hypertrophy.
AB  - INTRODUCTION: The minimum criterion for the diagnosis of hypertrophic
      cardiomyopathy (HCM) is thickening of the left ventricular wall, typically in an
      asymmetrical or focal fashion, and it requires no functional deficit. Using this
      criterion, we identified a family with four affected individuals and a single
      unrelated individual essentially with restrictive cardiomyopathy (RCM). Mutations
      in genes coding for the thin filaments of cardiac muscle have been described in
      RCM and HCM with 'restrictive features'. One such gene encodes for cardiac
      troponin I (TNNI3), a sub-unit of the troponin complex involved in the regulation
      of striated muscle contraction. We hypothesised that mutations in TNNI3 could
      underlie this particular phenotype, and we therefore screened TNNI3 for mutations
      in 115 HCM probands. METHODS: Clinical investigation involved examination,
      echocardiography, chest X-ray and an electrocardiogram of both the index cases
      and close relatives. The study cohort consisted of 113 South African HCM
      probands, with and without known founder HCM mutations, and 100 ethnically
      matched control individuals. Mutation screening of TNNI3 for diseasecausing
      mutations were performed using high-resolution melt (HRM) analysis. RESULTS: HRM
      analyses identified three previously described HCM-causing mutations (p.Pro82Ser,
      p.Arg162Gln, p.Arg170Gln) and a novel exonic variant (p.Leu144His). A previous
      study involving the same amino acid identified a p.Leu144Gln mutation in a
      patient presenting with RCM, with clinical features of HCM. We observed the novel
      p.Leu144His mutation in three siblings with clinical RCM and varying degrees of
      ventricular hypertrophy. The isolated index case with the de novo p.Arg170Gln
      mutation presented with a similar phenotype. Both mutations were absent in a
      healthy control group. CONCLUSION: We have identified a novel disease-causing
      p.Leu144His mutation and a de novo p.Arg170Gln mutation associated with RCM and
      focal ventricular hypertrophy, often below the typical diagnostic threshold for
      HCM. Our study provides information regarding TNNI3 mutations underlying RCM in
      contrast to other causes of a similar presentation, such as constrictive
      pericarditis or infiltration of cardiac muscle, all with marked right-sided
      cardiac manifestations. This study therefore highlights the need for extensive
      mutation screening of genes encoding for sarcomeric proteins, such as TNNI3 to
      identify the underlying cause of this particular phenotype.

PMID- 25940121
TI  - Development of the roadmap and guidelines for the prevention and management of
      high blood pressure in Africa: Proceedings of the PASCAR Hypertension Task Force
      meeting: Nairobi, Kenya, 27 October 2014.
AB  - Africa has one of the fastest growing economies in the world. The economic
      changes are associated with a health transition characterised by a rise in
      cardiovascular risk factors and complications, which tend to affect the African
      population at their age of maximum productivity. Recent data from Africa have
      highlighted the increasing importance of high blood pressure in this region of
      the world. This condition is largely underdiagnosed and poorly treated, and
      therefore leads to stroke, renal and heart failure, and death. Henceforth,
      African countries are taking steps to develop relevant policies and programmes to
      address the issue of blood pressure and other cardiovascular risk factors in
      response to a call by the World Health Organisation (WHO) to reduce premature
      deaths from non-communicable diseases (NCDs) by 25% by the year 2025 (25 * 25).
      The World Heart Federation (WHF) has developed a roadmap for global
      implementation of the prevention and management of raised blood pressure using a
      health system approach to help realise the 25 * 25 goal set by the WHO. As the
      leading continental organisation of cardiovascular professionals, the Pan-African
      Society of Cardiology (PASCAR) aims to contextualise the roadmap framework of the
      WHF to the African continent through the PASCAR Taskforce on Hypertension. The
      Taskforce held a workshop in Kenya on 27 October 2014 to discuss a process by
      which effective prevention and control of hypertension in Africa may be achieved.
      It was agreed that a set of clinical guidelines for the management of
      hypertension are needed in Africa. The ultimate goal of this work is to develop a
      roadmap for implementation of the prevention and management of hypertension in
      Africa under the auspices of the WHF. 

PMID- 25940120
TI  - HIV-associated large-vessel vasculopathy: a review of the current and emerging
      clinicopathological spectrum in vascular surgical practice.
AB  - An established relationship exists between human immunodeficiency virus (HIV) and
      the vascular system, which is characterised by clinical expressions of aneurysmal
      and occlusive disease that emanate from a common pathological process. The exact
      pathogenesis is currently unknown; attempts to implicate opportunistic pathogens
      have been futile. Theories converge on leucocytoclastic vasculitis with the vaso
      vasora as the vasculopathic epicentre. It is thought that the virus itself or
      viral proteins trigger the release of inflammatory mediators that cause
      endothelial dysfunction and smooth muscle proliferation leading to vascular
      injury and thrombosis. The beneficial effects of highly active anti-retroviral
      therapy alter the natural history of the disease profile and promote longevity
      but are negated by cardiovascular complications. Atherosclerosis is an emerging
      challenge. Presently patients are managed by standard surgical protocols because
      of non-existent universal surgical interventional guidelines. Clinical response
      to treatment is variable and often compounded by complications of graft
      occlusion, sepsis and poor wound healing. The clinical, imaging and pathological
      observations position HIV-associated large-vessel vasculopathy as a unique
      entity. This review highlights the spectrum of HIV-associated large-vessel
      aneurysmal, occlusive and atherosclerotic disease in vascular surgical practice. 

PMID- 25940122
TI  - Spontaneous coronary artery dissection associated with fibromuscular dysplasia.
AB  - This case presentation concerns a woman known to have fibromuscular dysplasia
      (FMD) who presented with an acute coronary syndrome (ACS). The coronary angiogram
      was considered to be normal. However, as spontaneous coronary artery dissection
      (SCAD) has a close association with FMD, subsequent meticulous review of the
      angiogram revealed a dissection within the circumflex coronary artery. SCAD
      causes 10% of ACS seen in women under 55 years of age. Both FMD and SCAD are
      underdiagnosed and SCAD may be overlooked or misdiagnosed on coronary
      angiography. The recommended management of SCAD differs from that of the usual
      presentations of ACS. For this reason, one should be alert to the possibility of
      SCAD when confronted by ACS in a younger woman, especially when she is known to
      have FMD. 

PMID- 25940123
TI  - Sudden cardiac death in low-resource settings: lessons from a resuscitated
      cardiac arrest.
AB  - We report on the case of an adult black African who was resuscitated from several
      cardiac arrests but suffered behavioural impairment, and discuss diagnostic
      pitfalls. The aetiology of coronary free lesion myocardial infarction with
      depressed left ventricular function was diagnosed when the patient travelled
      abroad. The low prevalence of recognised sudden cardiac arrest (SCA), as well as
      the lack of diagnostic and appropriate resuscitation facilities in parts of sub
      Saharan Africa lead to the mismanagement of victims. Increased awareness of SCA
      and its causes is urgently needed. 

PMID- 25940124
TI  - Two cases of cardiac sarcoidosis in pregnant women with supraventricular
      arrhythmia.
AB  - We present two cases of cardiac sarcoidosis whose first presentation was in
      pregnancy. All findings confirmed the diagnosis of sarcoidosis with cardiac
      involvement in both patients. The first patient, a 37-year-old, presented with
      dizziness and atrial fibrillation at 16 weeks' gestation. Echocardiography
      revealed thickened interventricular septum with a speckled pattern. Cardiac MRI
      after delivery showed myocardial oedema/inflammation corresponding with the same
      regions with early enhancement and epicardial delayed enhancement in the basal to
      mid-inferoseptal and basal anterior left ventricular myocardial segments.
      Transbronchial biopsy revealed histology of scanty fragments of inflamed
      bronchial mucosa. The second patient, a 31-year-old, was 17 weeks pregnant when
      she presented with daily palpitations and shortness of breath. She had prolonged
      episodes of supraventricular tachycardia. Echocardiography revealed a speckled
      septal and right ventricular wall pattern. Cardiac MRI after delivery showed
      basal and mid-ventricular mesocardial and epicardial enhancement, most compatible
      with sarcoidosis. 

PMID- 25940125
TI  - Relationship between femoral tunnel location and graft bending angle in outside
      in and transportal technique for ACL double bundle reconstruction in 3D-CT study.
AB  - INTRODUCTION: In anterior cruciate ligament (ACL) reconstruction, sharp
      angulation of the graft at tunnel aperture increases local strain to the graft.
      The purpose of this study is to investigate the relationship between femoral
      tunnel location and femoral graft bending angle after ACL double bundle
      reconstruction (ACL-DBR) with two different drilling techniques. MATERIALS AND
      METHODS: In ACL-DBR, femoral tunnel was created by two techniques; outside-in
      technique (26 patients, group A) and transportal technique (25 patients, group
      B). CT scan was taken at 1 week postoperatively. The position of femoral tunnel
      exit on the lateral femoral cortex, and intra-articular femoral and tibial tunnel
      aperture of the anteromedial bundle (AMB) and postero-lateral bundle (PLB) was
      measured using a rectangular frame on three-dimensional CT images. Femoral graft
      bending angle was measured using two-dimensional CT images. RESULTS: Femoral
      tunnel exits of AMB and PLB in group A were significantly anterior and proximal
      than those in group B (p < 0.05), while there was no significant difference in
      intra-articular femoral and tibial tunnel apertures between group A and B. A mean
      femoral graft bending angle of AMB was 80.3 degrees  in group A and 69.2 degrees
      in group B, respectively (p < 0.05). A mean femoral graft bending angle of PLB
      was 66.3 degrees  in group A and 64.6 degrees  in group B, respectively. In both
      groups, a significant (p < 0.05) correlation (r < -0.4) was observed between the
      position of the femoral tunnel exit (anterior-posterior ratio from femoral
      anterior border line) and the femoral graft bending angle in AMB. CONCLUSIONS:
      Since the femoral tunnel exit in outside-in technique was located more anterior
      and proximal, femoral graft bending angle of AMB in outside-in technique was
      greater than that in transportal technique. Anterior position of the femoral
      tunnel exit in AMB increased femoral graft bending angle in outside-in and
      transportal techniques.

PMID- 25940126
TI  - Total knee arthroplasty in patients with skeletal dysplasia.
AB  - INTRODUCTION: Dwarfism is a challenge in arthroplasty. The anatomical features
      provide a lot of pitfalls. The aim of this study was to follow-up growth
      restricted patients after endoprosthetic treatment. MATERIALS AND METHODS: 138
      knee arthroplasties in patients with a height <=150 cm between January 1, 2000
      and May 5, 2013 at our institution were enrolled in this study. 124 cases were
      available for 1-year follow-up. Out of these, 43 cases were available for 5-year
      follow-up so far. 14 patients were lost to follow-up. RESULTS: IKS score
      increased from 35 +/- 16 on admission to 67 +/- 22 (p < 0.001) at 1-year follow
      up and 65 +/- 23 (p < 0.001) at 5-year follow-up. Function Score increased from
      40 +/- 29 on admission to 64 +/- 21 (p < 0.001) at 1-year follow-up and 63 +/- 23
      (p < 0.001) at 5-year follow-up. Revision surgery was required in one case (0.8
      %) after 1-year follow-up, and in an additional three cases (7 %) after 5-year
      follow-up. CONCLUSIONS: Knee arthroplasty can be performed in patients suffering
      from dwarfism with good clinical benefits. However, survival rates are worse
      compared to the general population.

PMID- 25940127
TI  - Unicompartmental knee arthroplasty in patients with full versus partial thickness
      cartilage loss (PTCL): equal in clinical outcome but with higher reoperation rate
      for patients with PTCL.
AB  - PURPOSE: While the classical indications and contraindications for unicondylar
      knee arthroplasty (UKA) are widely accepted there is not yet consensus if
      patients with partial thickness cartilage loss (PTCL) are equally suited for
      treatment with UKA. The aim of our study was to determine if patients with
      partial thickness cartilage loss do equally well after treatment with UKA.
      METHODS: The study retrospectively analyzed the clinical results as well as the
      survival rates of 64 patients treated with UKA with the medial Oxford knee
      system. 32 patients had shown PTCL on preoperative radiographs, while the matched
      control group presented with full thickness cartilage loss (FTCL) medially.
      Outcome parameters were the Oxford Knee Score (OKS), the American Knee Society
      Score (AKS), and radiographic analysis. RESULTS: Postoperative improvement in OKS
      was 16 (SD 9.0) for patients with PTCL and 17 (SD 8.1) for patients with FTCL.
      There were no significant differences in the clinical scores between the two
      groups. Five Patients with PTCL had reoperation whereas there were only two in
      the bone on bone group. Cumulative survival at 5 years for all revisions was 84 %
      (95 % CI 72-92 %) for the PTCL group and 97 % (95 % CI 92-100 %) for the FTCL
      group. This difference was not yet significant (log rank: p = 0.095).
      CONCLUSIONS: Patients with PTCL are not equally suited for treatment with UKA
      like patients with bone on bone. Although PTCL has equal clinical results, it was
      associated with higher revision rates in our series.

PMID- 25940130
TI  - IL-14 and IL-16 are expressed in the thyroid of patients with either Graves'
      disease or Hashimoto's thyroiditis.
AB  - OBJECTIVES: Cytokines have an important role in orchestrating the pathophysiology
      in autoimmune thyroid disease. The aim of the current study was to analyse the
      expression of interleukin (IL)-14 and IL-16 in the thyroid tissue of patients
      with Graves' disease (GD), Hashimoto's thyroiditis (HT) or multinodular goitre
      (MNG) and in that of normal individuals, in patients' intrathyroidal CD4(+) and
      CD8(+) T cells, and in patient and normal cultured thyroid follicular cells.
      METHODS: The expression of IL-14 and IL-16 mRNA and protein was investigated
      using reverse transcription-polymerase chain reaction (RT-PCR) amplification, and
      Western blotting and ELISAs, respectively. RESULTS: IL-14 mRNA expression was
      detected in thyroid tissue from 8/9 GD, 3/4 HT and 3/13 MNG patients and 1/6
      normal individuals, and IL-16 mRNA expression in thyroid tissue from 9/9 GD, 4/4
      HT and 9/13 MNG patients and 4/6 normal individuals. IL-14 mRNA expression was
      detected in intrathyroidal CD4(+) and CD8(+) T cells from 2/2 GD and 2/2 HT
      patients, while IL-16 mRNA was detected in samples from 1/2 HT patients but not
      in those from either patient with GD. IL-14 and IL-16 mRNA expression was found
      in thyroid follicular cells derived from 2/2 patient with GD and 1/1 normal
      individual. IL-14 protein was detected in thyroid tissue from 6/6 GD, 1/1 HT and
      0/6 MNG patients and 0/6 normal individuals, and IL-16 protein in thyroid tissue
      from 6/6 GD, 1/1 HT and 1/6 MNG patients and 0/6 normal individuals. Expression
      of IL-14 protein was stimulated in thyroid follicular cells derived from two
      patients with GD and one normal individual by peripheral blood mononuclear cell
      (PBMC)-conditioned medium. Treatment of thyrocytes from two patients with GD and
      one normal individual with PBMC-conditioned medium and tumour necrosis factor
      (TNF)-alpha stimulated IL-16 protein expression. In normal thyrocytes, IL-16
      protein synthesis was induced also by IL-1beta, IL-17A, IL-4 and transforming
      growth factor (TGF)-beta. CONCLUSIONS: The data provide evidence that the
      intrathyroidal production of IL-14 and IL-16 is associated with the pathogenesis
      of autoimmune thyroid disease. Thyroid follicular cells display the ability to
      express IL-14 and IL-16 mRNA and can be stimulated to express IL-16 protein, by a
      panel of cytokines, and IL-14 protein, by as yet unidentified factors.

PMID- 25940131
TI  - Home-based primary care practices in the United States: current state and quality
      improvement approaches.
AB  - OBJECTIVES: To describe the characteristics of home-based primary care practices:
      staffing, administrative, population served, care practices, and quality of care
      challenges. DESIGN: Survey of home-based primary care practices. SETTING: Home
      based primary care practices in the United States. PARTICIPANTS: Members of the
      American Academy of Home Care Medicine and nonmember providers identified by
      surveyed members. MEASUREMENTS: A 58-item questionnaire that assessed practice
      characteristics, care provided by the practice, and how the quality of care that
      the practice provided was assessed. RESULTS: Survey response rate was 47.9%,
      representing 272 medical house calls practices. Mean average daily census was 457
      patients (median 100 patients, range 1-30,972 patients). Eighty-eight percent of
      practices offered around-the-clock coverage for urgent concerns, 60% held
      regularly scheduled team meetings, 89% used an electronic medical record, and one
      third used a defined quality improvement process. The following factors were
      associated with practices that used a defined quality improvement process:
      practice holds regularly scheduled team meetings to discuss specific patients
      (odds ratio (OR)=2.07, 95% confidence interval (CI)=1.02-4.21), practice conducts
      surveys of patients (OR=8.53, 95% CI=4.07-17.88), and practice is involved in
      National Committee for Quality Assurance patient-centered medical home (OR=3.27,
      95% CI=1.18-9.07). Ninety percent of practices would or might participate in
      quality improvement activities that would provide them timely feedback on patient
      and setting-appropriate quality indicators. CONCLUSIONS: There is a substantial
      heterogeneity of home-based primary care practice types. Most practices perform
      activities that lend themselves to robust quality improvement efforts, and nearly
      all indicated interest in a national registry to inform quality improvement.

PMID- 25940132
TI  - Charge carrier transport and photogeneration in P3HT:PCBM photovoltaic blends.
AB  - This article reviews the charge transport and photogeneration in bulk
      heterojunction solar cells made from blend films of regioregular poly(3
      hexylthiophene) (RR-P3HT) and methano-fullerene (PCBM). The charge transport,
      specifically the hole mobility in the RR-P3HT phase of the polymer:fullerene
      photovoltaic blend, is dramatically affected by thermal annealing. The hole
      mobility increases more than three orders of magnitude and reaches a value of up
      to 2 * 10(-4) cm(2) V(-1) s(-1) after the thermal annealing process as a result
      of an improved semi-crystallinity of the film. This significant increase of the
      hole mobility balances the electron and hole mobilities in a photovoltaic blend
      in turn reducing space-charge formation, and this is the most important factor
      for the strong enhancement of the photovoltaic efficiency compared to an as cast,
      that is, non-annealed device. In fact, the balanced charge carrier mobility in RR
      P3HT:PCBM blends in combination with a field- and temperature-independent charge
      carrier generation and greatly reduced non-geminate recombination explains the
      large quantum efficiencies mea-sured in P3HT:PCBM photovoltaic devices.

PMID- 25940133
TI  - Peritoneal dialysis and potassium: pains and gains in ED-the authors' reply.

PMID- 25940134
TI  - Early left ventricular free-wall rupture in non-STEMI never to be neglected.
AB  - As the most dramatic and fatal complication, left ventricular free-wall rupture
      (LVFWR) used to present in approximately 3% of patients with acute myocardial
      infarction. After the introduction of primary percutaneous coronary intervention,
      the incidence of LVFWR decreased but remained approximately 1.7%. Left
      ventricular free-wall rupture occurs in patients with transmural myocardial
      infarction, which is almost exclusively ST elevation myocardial infarction
      (STEMI). This condition carries a high mortality as a result of hemopericardium
      and cardiac tamponade. Left ventricular free-wall rupture rarely occurs in
      patients with non-ST-elevation myocardial infarction, but the risk of it cannot
      be ignored. This case describes early development LVFWR after non-ST-elevation
      myocardial infarction to evoke high vigilance of clinicians to this condition.

PMID- 25940136
TI  - Influenza, influenza-like symptoms and their association with cardiovascular
      risks: a systematic review and meta-analysis of observational studies.
AB  - AIMS: To synthesise the evidence relating influenza and influenza-like symptoms
      to the risks of myocardial infarction (MI), heart failure (HF) and stroke.
      METHODS: We conducted a systematic review and meta-analysis of the evidence
      relating influenza and influenza-like symptoms to the risks of MI, HF and stroke.
      We systematically searched all MEDLINE and EMBASE entries up to August 2014 for
      studies of influenza vs. the cardiovascular outcomes above. We conducted random
      effects meta-analysis using inverse variance method for pooled odds ratios (OR)
      and evaluated statistical heterogeneity using the I(2) statistic. RESULTS: We
      identified 12 studies with a total of 84,003 participants. The pooled OR for risk
      of MI vs. influenza (serologically confirmed) was 1.27 (95% CI, confidence
      interval 0.54-2.95), I(2)  = 47%, which was significant for the only study that
      adjusted for confounders (OR 5.50, 95% CI 1.31-23.13). The pooled OR for risk of
      MI vs. influenza-like symptoms was 2.17 (95% CI 1.68-2.80), I(2)  = 0%, which was
      significant for both unadjusted (OR 2.23, 95% CI 1.65-3.01, five studies) and
      adjusted studies (OR 2.01, 95% CI 1.24-3.27, two studies). We found one study
      that evaluated stroke risk, one study in patients with HF, and one that evaluated
      mortality from MI - all of these studies suggested increased risks of events with
      influenza-like symptoms. CONCLUSIONS: There is an association between influenza
      like illness and cardiovascular events, but the relationship is less clear with
      serologically diagnosed influenza. We recommend renewed efforts to apply current
      clinical guidelines and maximise the uptake of annual influenza immunisation
      among patients with cardiovascular diseases, to decrease their risks of MI and
      stroke.

PMID- 25940135
TI  - Chronic ethanol exposure decreases CB1 receptor function at GABAergic synapses in
      the rat central amygdala.
AB  - The endogenous cannabinoids (eCBs) influence the acute response to ethanol and
      the development of tolerance, dependence and relapse. Chronic alcohol exposure
      alters eCB levels and Type 1 cannabinoid receptor (CB1 ) expression and function
      in brain regions associated with addiction. CB1 inhibits GABA release, and
      GABAergic dysregulation in the central nucleus of the amygdala (CeA) is critical
      in the transition to alcohol dependence. We investigated possible disruptions in
      CB1 signaling of rat CeA GABAergic transmission following intermittent ethanol
      exposure. In the CeA of alcohol-naive rats, CB1 agonist WIN 55,212-2 (WIN)
      decreased the frequency of spontaneous and miniature GABAA receptor-mediated
      inhibitory postsynaptic currents (s/mIPSCs). This effect was prevented by CB1
      antagonism, but not Type 2 cannabinoid receptor (CB2 ) antagonism. After 2-3
      weeks of intermittent ethanol exposure, these WIN inhibitory effects were
      attenuated, suggesting ethanol-induced impairments in CB1 function. The CB1
      antagonist AM251 revealed a tonic eCB/CB1 control of GABAergic transmission in
      the alcohol-naive CeA that was occluded by calcium chelation in the postsynaptic
      cell. Chronic ethanol exposure abolished this tonic CB1 influence on mIPSC, but
      not sIPSC, frequency. Finally, acute ethanol increased CeA GABA release in both
      naive and ethanol-exposed rats. Although CB1 activation prevented this effect,
      the AM251- and ethanol-induced GABA release were additive, ruling out a direct
      participation of CB1 signaling in the ethanol effect. Collectively, these
      observations demonstrate an important CB1 influence on CeA GABAergic transmission
      and indicate that the CeA is particularly sensitive to alcohol-induced
      disruptions of CB1 signaling.

PMID- 25940137
TI  - Clusterin/Apolipoprotein J immunoreactivity is associated with white matter
      damage in cerebral small vessel diseases.
AB  - AIM: Brain clusterin is known to be associated with the amyloid-beta deposits in
      Alzheimer's disease (AD). We assessed the distribution of clusterin
      immunoreactivity in cerebrovascular disorders, particularly focusing on white
      matter changes in small vessel diseases. METHODS: Post-mortem brain tissues from
      the frontal or temporal lobes of a total of 70 subjects with various disorders
      including cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL), cerebral amyloid angiopathy (CAA) and AD were
      examined using immunohistochemistry and immunofluorescence. We further used
      immunogold electron microscopy to study clusterin immunoreactivity in
      extracellular deposits in CADASIL. RESULTS: Immunostaining with clusterin
      antibodies revealed strong localization in arterioles and capillaries, besides
      cortical neurones. We found that clusterin immunostaining was significantly
      increased in the frontal white matter of CADASIL and pontine autosomal dominant
      microangiopathy and leukoencephalopathy subjects. In addition, clusterin
      immunostaining correlated with white matter pathology severity scores.
      Immunostaining in axons ranged from fine punctate deposits in single axons to
      larger confluent areas with numerous swollen axon bulbs, similar to that observed
      with known axon damage markers such as non-phosphorylated neurofilament H and the
      amyloid precursor protein. Immunofluorescence and immunogold electron microscopy
      experiments showed that whereas clusterin immunoreactivity was closely associated
      with vascular amyloid-beta in CAA, it was lacking within the granular osmiophilic
      material immunolabelled by NOTCH3 extracelluar domain aggregates found in
      CADASIL. CONCLUSIONS: Our results suggest a wider role for clusterin associated
      with white matter damage in addition to its ability to chaperone proteins for
      clearance via the perivascular drainage pathways in several disease states.

PMID- 25940138
TI  - Acyl-CoA-binding domain containing 3 modulates NAD+ metabolism through activating
      poly(ADP-ribose) polymerase 1.
AB  - NAD(+) plays essential roles in cellular energy homoeostasis and redox state,
      functioning as a cofactor along the glycolysis and citric acid cycle pathways.
      Recent discoveries indicated that, through the NAD(+)-consuming enzymes, this
      molecule may also be involved in many other cellular and biological outcomes such
      as chromatin remodelling, gene transcription, genomic integrity, cell division,
      calcium signalling, circadian clock and pluripotency. Poly(ADP-ribose) polymerase
      1 (PARP1) is such an enzyme and dysfunctional PARP1 has been linked with the
      onset and development of various human diseases, including cancer, aging,
      traumatic brain injury, atherosclerosis, diabetes and inflammation. In the
      present study, we showed that overexpressed acyl-CoA-binding domain containing 3
      (ACBD3), a Golgi-bound protein, significantly reduced cellular NAD(+) content via
      enhancing PARP1's polymerase activity and enhancing auto-modification of the
      enzyme in a DNA damage-independent manner. We identified that extracellular
      signal-regulated kinase (ERK)1/2 as well as de novo fatty acid biosynthesis
      pathways are involved in ACBD3-mediated activation of PARP1. Importantly,
      oxidative stress-induced PARP1 activation is greatly attenuated by knocking down
      the ACBD3 gene. Taken together, these findings suggest that ACBD3 has prominent
      impacts on cellular NAD(+) metabolism via regulating PARP1 activation-dependent
      auto-modification and thus cell metabolism and function. 

PMID- 25940139
TI  - A Chromosome 17 Locus Engenders Frequency-Specific Non-Progressive Hearing Loss
      that Contributes to Age-Related Hearing Loss in Mice.
AB  - The 129S6/SvEvTac (129S6) inbred mouse is known for its resistance to noise
      induced hearing loss (NIHL). However, less is understood of its unique age
      related hearing loss (AHL) phenotype and its potential relationship with the
      resistance to NIHL. Here, we studied the physiological characteristics of hearing
      loss in 129S6 and asked if noise resistance (NR) and AHL are genetically linked
      to the same chromosomal region. We used auditory brainstem response (ABR) and
      distortion product otoacoustic emissions (DPOAE) to examine hearing sensitivity
      between 1 and 13 months of age of recombinant-inbred (congenic) mice with an NR
      phenotype. We identified a region of proximal chromosome (Chr) 17 (D17Mit143
      D17Mit100) that contributes to a sensory, non-progressive hearing loss (NPHL)
      affecting exclusively the high-frequencies (>24 kHz) and maps to the nr1 locus on
      Chr 17. ABR experiments showed that 129S6 and CBA/CaJ F1 (CBACa) hybrid mice
      exhibit normal hearing, indicating that the hearing loss in 129S6 mice is
      inherited recessively. An allelic complementation test between the 129S6 and
      101/H (101H) strains did not rescue hearing loss, suggesting genetic allelism
      between the nphl and phl1 loci of these strains, respectively. The hybrids had a
      milder hearing loss than either parental strain, which indicate a possible
      interaction with other genes in the mouse background or a digenic interaction
      between different genes that reside in the same genomic region. Our study defines
      a locus for nphl on Chr 17 affecting frequencies greater than 24 kHz.

PMID- 25940140
TI  - Weight Loss, the Obesity Paradox, and the Risk of Death in Rheumatoid Arthritis.
AB  - OBJECTIVE: In contrast to what is observed in the general population, a low body
      mass index (BMI) has been associated with accelerated mortality in patients with
      rheumatoid arthritis (RA). The aim of this study was to assess whether weight
      loss might explain these seemingly paradoxical observations. METHODS: Our study
      included patients identified from the Veterans Affairs (VA) RA Registry. Dates of
      death were abstracted from VA electronic medical records. The BMI at each study
      visit and the change from the previous visit were determined. The maximum BMI of
      each patient was also obtained from medical records. The annualized rate of BMI
      loss was determined from the slope of change (per year) in BMI over visits within
      the preceding 13 months. Cox multivariable proportional hazards models were used
      to assess associations between BMI measures and mortality. RESULTS: In a sample
      of 1,674 patients, 312 deaths occurred over 9,183 person-years. A loss in BMI of
      >=1 kg/m(2) was associated with a greater risk of death, after adjustment for
      demographics, comorbidities, BMI, smoking, and RA therapies (hazard ratio [HR]
      1.99, 95% confidence interval [95% CI] 1.53-2.59, P < 0.001). This association
      remained significant in a subsample analysis adjusting for C-reactive protein and
      physical function (HR 1.81, 95% CI 1.36-2.41, P < 0.001). Weight loss at an
      annualized rate of >=3 kg/m(2) was associated with the greatest risk of death (HR
      2.49, 95% CI 1.73-3.57, P < 0.001). Low BMI (<20 kg/m(2) ) in patients with a
      history of obesity (>30 kg/m(2) ) was associated with the greatest risk (HR 8.52,
      95% CI 4.10-17.71, P < 0.001). CONCLUSION: Weight loss is a strong predictor of
      death in patients with RA. These observations may explain the observed obesity
      paradox and do not support a biologically protective role of obesity.

PMID- 25940141
TI  - Ineffective breathing pattern in children and adolescents with congenital heart
      disease: accuracy of defining characteristics.
AB  - AIMS AND OBJECTIVES: The purpose of this study was to assess the prevalence of
      ineffective breathing pattern and the accuracy of its defining characteristics,
      among children and adolescents with congenital heart disease. BACKGROUND: The
      NANDA International nursing diagnosis, ineffective breathing pattern, has been
      noted to have high prevalence in different clinical contexts and age groups.
      Despite that, nurses continue to report difficulties in confirming this
      diagnosis. The lack of data regarding the sensitivity, specificity and predictive
      values of the defining characteristics contribute to decreased certainty in
      diagnosing ineffective breathing pattern. DESIGN: A diagnostic accuracy study.
      METHODS: This study of diagnostic accuracy was conducted with 61 children and
      adolescents with congenital heart disease. Two nurses were trained by the primary
      investigator on use of defining characteristics in the diagnostic process for
      ineffective breathing pattern. RESULTS: Ineffective breathing pattern was present
      in 26.2% of the children and adolescents sampled. When analysing the defining
      characteristics, alterations in depth of breathing, showed high values of
      sensitivity and specificity. In addition, orthopnoea, tachypnoea and use of
      accessory muscles to breathe, showed high values of specificity; dyspnoea showed
      high values of sensitivity. Finally, assumption of three-point position,
      bradypnoea and increased anterior-posterior diameter were not found to be
      statistically significant for this sample population. CONCLUSION: Five defining
      characteristics of ineffective breathing pattern presented measures of accuracy
      with statistically significant values in children with congenital heart disease.
      RELEVANCE TO CLINICAL PRACTICE: The findings can help nurses during the
      diagnostic process, as they identify which defining characteristics can be used
      to confirm or rule out the probability of occurrence of the diagnosis.

PMID- 25940142
TI  - [Esophageal motility disorders].
AB  - Esophageal motility disorders are a group of diseases that result in swallowing
      dysfunction due to changes in neuromuscular structures, which coordinate
      esophageal function. Besides achalasia, which is the best defined functional
      disturbance of the esophagus, there are other motility disorders, namely
      hypercontractile (diffuse esophageal spasm, nutcracker or jackhammer esophagus,
      hypertensive lower esophageal sphincter) and hypocontractile disorders, whose
      origins and disease mechanisms are not yet well understood. The main symptoms are
      dysphagia and thoracic pain. Diagnosis is usually made by means of esophageal
      manometry, while endoscopy and barium swallow are essential to exclude
      inflammatory or neoplastic changes. The introduction of high resolution manometry
      (HRM) with up to 36 pressure points that are simultaneously measured on the
      esophageal catheter has changed diagnosis and assessment, and has led-with the
      Chicago Classification-to a new functional classification of esophageal motility
      disorders. In the following review, the most important motility disorders of the
      esophagus are introduced.

PMID- 25940143
TI  - [Gastroparesis. Definition, diagnostics, and therapy].
AB  - Gastroparesis is characterized by a constellation of upper gastrointestinal
      symptoms in association with delayed gastric emptying in the absence of
      mechanical outlet obstruction from the stomach. Major symptoms are nausea,
      vomiting, early satiety or postprandial fullness, bloating, and abdominal or
      epigastric pain. Idiopathic, diabetic, and postsurgical causes represent the most
      common etiologies. Diagnostic procedures for the evaluation of gastroparesis
      comprise gastric emptying scintigraphy (gold standard), (13)C-octanoate breath
      testing, and a wireless motility capsule. Management of gastroparesis includes
      normalization of nutritional state, relief of symptoms, glycemic control, and
      improvement of gastric emptying. Medical treatment entails use of prokinetic
      drugs, which are currently the first-line therapy. Nausea and vomiting might be
      positively influenced by antiemetic drugs. Gastric electronic stimulation and
      surgical interventions should be used in well-defined patients and represent a
      therapeutic option in tertiary centers. 

PMID- 25940144
TI  - [Motility disorders of the colon].
AB  - The motility of the colon is modulated by the enteric nervous system. It is very
      complex, governing backward and forward movements of the feces. Primary megacolon
      and megarectum are clinically diverse. Megacolon refractory to laxative treatment
      may be subject to colectomy, while megarectum should be treated by consistent
      laxation. Acute colonic pseudo-obstruction may occur with severe systemic
      diseases and electrolyte disturbances or it may be postoperatively and/or
      medically induced. A small proportion of chronically constipated patients suffer
      from slow transit constipation, others from disordered defecation. In the
      remaining patients no objective cause of the complaints may be found. In slow
      transit constipation, propulsive colonic motility is disturbed, dietary fiber is
      ineffective, and the response to bisacodyl is blunted. Pelvic floor dyssynergia
      is characterized by a voluntary (although unconscious) contraction of the anal
      sphincter simultaneously with the abdominal muscles. It can be treated by
      avoiding straining and by sphincter training. 

PMID- 25940148
TI  - Preparation, characterization and application of a new 25,27-bis-[2-(5
      methylthiadiazole)thioethoxyl]-26,28-dihydroxy-para-tert-butyl calix[4]arene
      stationary phase for HPLC.
AB  - A new para-tert-butylcalix[4]arene column containing thiadiazole functional
      groups was prepared and used for the separation of polycyclic aromatic
      hydrocarbons, phenolic compounds, aromatic amines, benzoic acid and its
      derivatives by high-performance liquid chromatography (HPLC). The effect of
      organic modifier content in the mobile phase on retention and selectivity of
      these compounds were investigated. The results indicate that the stationary phase
      behaves like reversed-phase packing. However, hydrogen bonding, pi-pi and
      inclusion interactions seem to be involved in the separation process. The column
      has been successfully employed for the analysis of clenbuterol in pork and pig
      casing; the limit of detection and the limit of quantitation for this method by
      HPLC-UV detection was 0.03 and 0.097 MUg/mL, respectively; the method is
      demonstrated to be suitable and a competitive alternative analytical method for
      the determination of clenbuterol. 

PMID- 25940145
TI  - COUP-TFII Stimulates Dentin Sialophosphoprotein Expression and Mineralization in
      Odontoblasts.
AB  - Chicken ovalbumin upstream promoter transcription factor 2 (COUP-TFII), an orphan
      nuclear receptor belonging to the steroid-thyroid hormone receptor superfamily,
      plays an important role in cell fate determination of various tissues. However,
      the specific role of COUP-TFII in tooth development has not yet been elucidated.
      In the present study, we aimed to explore the role of COUP-TFII in dentin
      sialophosphoprotein (DSPP) expression and matrix mineralization in odontoblast
      lineage cells. In primary human dental pulp cells (HDPCs) and murine dental
      papilla-derived cells (MDPC-23) cultured in a mineralizing medium, the expression
      of COUP-TFII was induced along with the increased odontoblast-specific dentin
      matrix protein-1 (DMP-1) and DSPP expression. Endogenous expression of COUP-TFII
      in maxillary second molar germs of rats showed an increasing tendency as
      development of the tooth progressed. Also, COUP-TFII protein was detected in
      greater quantity in the odontoblastic layer of second molar germs than in that of
      third molar germs of rats. Overexpression of COUP-TFII using an adenoviral system
      upregulated the expression of odontoblast-specific genes with increased alkaline
      phosphatase activity and matrix mineralization in odontoblast-lineage cells. In
      contrast, knockdown of COUP-TFII using small interfering RNA decreased the
      expression of odontoblast-specific genes, which reduced matrix mineralization.
      Mechanistic studies revealed that COUP-TFII increased DSPP transcription by
      direct binding on the DSPP promoter. In addition, COUP-TFII physically interacted
      with the homeodomain transcription factor Msx2 and antagonistically regulated the
      Msx2 effect on DSPP promoter activity. Taken together, these results suggest that
      COUP-TFII has a stimulatory role in DSPP expression and matrix mineralization in
      odontoblast-lineage cells. 

PMID- 25940149
TI  - Laparoscopic surgery for colorectal cancer is safe and has survival outcomes
      similar to those of open surgery in elderly patients with a poor performance
      status: subanalysis of a large multicenter case-control study in Japan.
AB  - BACKGROUND: It remains controversial whether open or laparoscopic surgery should
      be indicated for elderly patients with colorectal cancer and a poor performance
      status. METHODS: In those patients aged 80 years or older with Eastern
      Cooperative Oncology Group performance status score of 2 or greater who received
      elective surgery for stage 0 to stage III colorectal adenocarcinoma and had no
      concomitant malignancies and who were enrolled in a multicenter case-control
      study entitled "Retrospective study of laparoscopic colorectal surgery for
      elderly patients" that was conducted in Japan between 2003 and 2007, background
      characteristics and short-term and long-term outcomes for open surgery and
      laparoscopic surgery were compared. RESULTS: Of the 398 patients included, 295
      underwent open surgery and 103 underwent laparoscopic surgery. There were no
      significant differences in the baseline characteristics between open surgery and
      laparoscopic surgery patients, except for previous abdominal surgery and TNM
      stage. The median operation duration was shorter with open surgery (open surgery,
      153 min; laparoscopic surgery, 202 min; P < 0.001), and less blood loss occurred
      with laparoscopic surgery (median open surgery, 109 g; median laparoscopic
      surgery, 30 g; P < 0.001). An operation duration of 180 min or more (odds ratio,
      1.97; 95 % confidence interval, 1.17-3.37; P = 0.011) and selection of
      laparoscopic surgery (odds ratio, 0.41; 95 % confidence interval, 0.22-0.75; P =
      0.003) were statistically significant in the multivariate analysis for
      postoperative morbidity. Moreover, laparoscopic surgery did not result in an
      inferior overall survival rate compared with open surgery (log-rank test P =
      0.289, 0.278, 0.346, 0.199, for all-stage, stage 0-I, stage II, and stage III
      disease, respectively). CONCLUSIONS: Laparoscopic surgery in elderly colorectal
      cancer patients with a poor performance status is safe and not inferior to open
      surgery in terms of overall survival.

PMID- 25940151
TI  - Proton pump inhibitor after endoscopic resection for esophageal squamous cell
      cancer: multicenter prospective randomized controlled trial.
AB  - BACKGROUND: Whether proton pump inhibitors (PPIs) relieve heartburn or precordial
      pain after endoscopic resection (ER) for esophageal squamous cell carcinoma
      (ESCC) remains unclear. The aim of this study was to investigate the efficacy of
      PPI therapy for these symptoms after ER for ESCC. METHODS: We conducted a
      multicenter prospective randomized controlled trial among 15 hospitals in Japan.
      In total, 229 patients with cT1a ESCC were randomly assigned to receive PPI
      therapy for 5 weeks after ER (the PPI group, n = 115) or follow-up without PPI
      therapy (the non-PPI group, n = 114). The primary end point was the incidence of
      gastroesophageal reflux disease (GERD)-like symptoms after ER from a self
      reported questionnaire (Frequency Scale for Symptoms of GERD). Secondary end
      points were ulcer healing rate at 5 weeks, incidence of pain, improvement rate of
      symptoms in those who started PPI therapy because of GERD-like symptoms in the
      non-PPI group, and adverse events. RESULTS: No significant difference was
      observed in the incidence of GERD-like symptoms after ER between the non-PPI and
      PPI groups (30 % vs 34 %, respectively). No significant differences were observed
      in the ulcer healing rate at 5 weeks (84 % vs 85 %) and incidence of pain within
      1 week (36 % vs 45 %). In nine of ten patients (90 %) who started PPI therapy
      because of GERD-like symptoms in the non-PPI group, PPI administration relieved
      GERD-like symptoms. No adverse events related to PPI administration were
      observed. CONCLUSION: PPI therapy is not efficacious in reducing symptoms and did
      not promote healing of ulcers in patients undergoing ER for ESCC.

PMID- 25940152
TI  - Application of (1)h NMR profiling to assess seed metabolomic diversity. A case
      study on a soybean era population.
AB  - (1)H NMR spectroscopy offers advantages in metabolite quantitation and platform
      robustness when applied in food metabolomics studies. This paper provides a (1)H
      NMR-based assessment of seed metabolomic diversity in conventional and glyphosate
      resistant genetically modified (GM) soybean from a genetic lineage representing
      ~35 years of breeding and differing yield potential. (1)H NMR profiling of
      harvested seed allowed quantitation of 27 metabolites, including free amino
      acids, sugars, and organic acids, as well as choline, O-acetylcholine,
      dimethylamine, trigonelline, and p-cresol. Data were analyzed by canonical
      discriminant analysis (CDA) and principal variance component analysis (PVCA).
      Results demonstrated that (1)H NMR spectroscopy was effective in highlighting
      variation in metabolite levels in the genetically diverse sample set presented.
      The results also confirmed that metabolite variability is influenced by selective
      breeding and environment, but not genetic modification. Therefore, metabolite
      variability is an integral part of crop improvement that has occurred for decades
      and is associated with a history of safe use.

PMID- 25940153
TI  - Silicosis and chronic renal disease.
AB  - BACKGROUND: Silica has been associated with end stage kidney disease and kidney
      dysfunction. METHODS: Calculated glomerular filtration rate, history of kidney
      disease or chronic dialysis, elevated serum creatinine, and stages of chronic
      kidney disease among silicotics identified in Michigan's Silicosis Surveillance
      System from 1987 to 2009 were reviewed to determine the prevalence of kidney
      disease in confirmed cases of silicosis. RESULTS: Twenty-four percent of 1,072
      silicotics had a measure of kidney dysfunction (32.3% if diabetes or hypertension
      present vs. 20.2% if not). Sixty-nine percent of silicotics had Stage I or
      greater chronic kidney dysfunction versus 38.8% of the U.S. general population
      >=60 years. No association was found between kidney function and measures of
      silica exposure. CONCLUSIONS: Individuals with silicosis have an increased
      prevalence of kidney disease. More work to define the pathological changes
      associated with silica exposure is needed to understand the cause of silica's
      adverse effect on the kidney.

PMID- 25940150
TI  - A breakthrough in probiotics: Clostridium butyricum regulates gut homeostasis and
      anti-inflammatory response in inflammatory bowel disease.
AB  - Intestinal immune homeostasis is regulated by gut microbiota, including
      beneficial and pathogenic microorganisms. Imbalance in gut bacterial constituents
      provokes host proinflammatory responses causing diseases such as inflammatory
      bowel disease (IBD). The development of next-generation sequencing technology
      allows the identification of microbiota alterations in IBD. Several studies have
      shown reduced diversity in the gut microbiota of patients with IBD. Advances in
      gnotobiotic technology have made possible analysis of the role of specific
      bacterial strains in immune cells in the intestine. Using these techniques, we
      have shown that Clostridium butyricum as a probiotic induces interleukin-10
      producing macrophages in inflamed mucosa via the Toll-like receptor 2/myeloid
      differentiation primary response gene 88 pathway to prevent acute experimental
      colitis. In this review, we focus on the new approaches for the role of specific
      bacterial strains in immunological responses, as well as the potential of
      bacterial therapy for IBD treatments.

PMID- 25940154
TI  - Selective computed tomographic angiography in traumatic subarachnoid hemorrhage:
      a pilot study.
AB  - BACKGROUND: Computed tomographic angiography (CTA) tends to be overused in
      patients with traumatic subarachnoid hemorrhage (tSAH) to rule out intracranial
      aneurysmal disease. We hypothesized that there are two exclusive subsets of
      patients with tSAH that maybe at increased risk for aneurysm and thus should
      undergo CTA, those "found down" with an unknown mechanism of injury and those
      with "central subarachnoid hemorrhage" (CSH, in the subarachnoid cisterns and
      Sylvian fissures). This pilot study was performed to provide more information on
      the validity of our hypothesis. METHODS: A retrospective analysis was performed
      on trauma patients with tSAH who underwent CTA of the brain. Patients presented
      to a level I trauma center from January 2008-December 2012. Our principal outcome
      was the diagnosis of an intracranial aneurysm. Student t-test, chi-squared test,
      Mann-Whitney U test, and binary logistic regression were used for statistical
      analysis, with significance set at alpha = 0.05. RESULTS: Of 617 total patients
      with tSAH, 186 patients underwent CTA. Majority of patients were male (64%), with
      median age of 56 y. Median Glasgow coma scale on presentation was 15, and the
      median injury severity score was 16. Thirteen patients (6.99%) had an aneurysm on
      the follow-up CTA. Of those, 8 of 13 (61.5%) were felt to have presented with a
      ruptured aneurysm. Among those, 5 of 8 (62.5%) sustained a fall and 3 of 8
      (37.5%) resulted from a motor vehicle crash. Among the 14 patients (7.5%) "found
      down", none had an aneurysm. All eight patients with a ruptured aneurysm (100%)
      had CSH, whereas none of the five patients with unruptured aneurysm had CSH. On
      multivariate analysis, suprasellar cistern hemorrhage was the most predictive
      noncontrast computed tomographic finding with regard to aneurysm presence (odds
      ratio, 4.78; 95% confidence interval, 1.33-17.1). Patients with an aneurysmal
      disease had a significantly higher mean arterial pressure on presentation
      (median, 115 mm Hg) than those without an aneurysm (median, 96 mm Hg, P < 0.05).
      Of the eight ruptured aneurysms, six underwent neurosurgical clipping or coiling,
      one underwent a ventriculostomy, and one underwent a craniotomy for evacuation of
      hemorrhage. CONCLUSIONS: These preliminary data support a more selective approach
      to screening CTAs in patients with tSAH. CTA should be used in those patients
      with CSH regardless of mechanism of injury. A more restrictive approach should be
      used in patients with only peripheral subarachnoid hemorrhage.

PMID- 25940155
TI  - Intraoperative ultrasound for liver tumor resection in children.
AB  - BACKGROUND: Primary hepatic neoplasms in children are rare tumors. All malignant
      and medically refractive benign primary pediatric liver tumors ultimately require
      surgical resection for cure. Accurate preoperative imaging including
      multidetector helical computerized tomography or magnetic resonance imaging (MRI)
      is necessary to determine resectability. In the literature intraoperative
      ultrasound (IOUS) has proven to be a vital adjunct to liver surgery in adults,
      but this is not well established in children. MATERIALS AND METHODS: Between
      April 2003 and November 2014, children (<18-y-old) with a primary liver neoplasm,
      preoperatively evaluated with multidetector helical computerized tomography or
      MRI, who had IOUS used at the time of surgery were retrospectively reviewed.
      RESULTS: Preoperative evaluation with high-resolution MRI and IOUS were
      discordant in 4 of 19 patients (21%). In one case, right hepatic vein involvement
      was not accurately assessed with MRI. Two cases showed tumor involvement in
      segment IV by MRI; however, IOUS revealed no medial segment involvement. The
      final patient had a large (>5 cm), solitary hepatic adenoma on MRI, but IOUS in
      this case revealed diffuse adenomatosis. The operative management was altered in
      three of these cases. CONCLUSIONS: Although MRI can provide a detailed view of
      the hepatic anatomy and is an invaluable tool for preoperative planning for the
      pediatric patient with a primary liver neoplasm, IOUS may provide further and
      more up to date delineation of tumor extent and should be considered a crucial
      element in operative planning for hepatectomy in children.

PMID- 25940157
TI  - Environmental-mediated intestinal homeostasis in neonatal mice.
AB  - BACKGROUND: Immunoglobulin A (IgA) plays a key role in coating luminal antigens
      and preventing translocation of harmful bacteria. The aryl hydrocarbon receptor
      (AhR) is a basic helix-loop-helix transcription factor that when stimulated
      activates factors important for barrier function and intestinal homeostasis. We
      hypothesize that AhR signaling is critical for establishment of intestinal
      homeostasis in neonates. MATERIAL AND METHODS: Mice: C57BL/6 (B6) AhR+/+ wild
      type (WT), B6.AhR-/- Aryl-hydrocarbon receptor knockout (KO), and B6.AhR+/+
      raised on an AhR ligand-free diet (AhR LF). Enzyme-linked immunosorbent assay was
      used to measure fecal and serum IgA levels. Bacterial translocation was measured
      by culturing the mesenteric lymph nodes. RESULTS: Two week old KO mice had
      significantly less fecal IgA compared with WT (and AhR LF, P value = 0.0393. The
      amount of IgA from the gastric contents of 2-wk-old mice was not significantly
      different. At age 8 wk, AhR LF mice had significantly less fecal IgA than WT and
      KO P value = 0.0077. At 2 wk, KO mice had significantly higher levels of
      bacterial translocation and at 8 wk AhR LF had significantly higher levels of
      bacterial translocation compared with WT. CONCLUSIONS: In neonatal mice, the lack
      of AhR signaling is associated with loss of intestinal homeostasis, evidenced by
      decreased levels of IgA and increased bacterial translocation. In adult mice,
      exogenous AhR ligand and not receptor signaling is necessary for maintenance of
      intestinal integrity.

PMID- 25940156
TI  - A rapid, reproducible, noninvasive predictor of liver graft survival.
AB  - BACKGROUND: Clinical and laboratory criteria are not reliable predictors of
      deceased donor liver graft quality. Intraoperative assessment of experienced
      surgeons is the gold standard. Standardizing and quantifying this assessment is
      especially needed now that regional sharing is the rule. We prospectively
      evaluated a novel, simple, rapid, noninvasive, quantitative measure of liver
      function performed before graft procurement. MATERIALS AND METHODS: Using a
      portable, finger-probe-based device, indocyanine green plasma disappearance rates
      (ICG-PDR) were measured in adult brain-dead donors in the local donor service
      area before organ procurement. Results were compared with graft function and
      outcomes. Both donor and recipient teams were blinded to ICG-PDR measurements.
      RESULTS: Measurements were performed on 53 consecutive donors. Eleven liver
      grafts were declined by all centers because of quality; the other 42 grafts were
      transplanted. Logistic regression analysis showed ICG-PDR to be the only donor
      variable to be significantly associated with 7-d graft survival. Donor risk
      index, donor age, and transaminase levels at peak or procurement were not
      significantly associated with 7-d graft survival. CONCLUSIONS: We report the
      successful use of a portable quantitative means of measuring liver function and
      its association with graft survival. These data warrant further exploration in a
      variety of settings to evaluate acceptable values for donated liver grafts.

PMID- 25940158
TI  - Recommendations for including surgery on the public health agenda.
AB  - BACKGROUND: Surgical care has made limited inroads on the public health and
      global health agendas despite increasing data showing the enormous need. The
      objective of this study was to survey interested members of a global surgery
      community to identify patterns of thought regarding barriers to political
      priority. MATERIALS AND METHODS: All active members of the nongovernmental
      organization Surgeons OverSeas were surveyed and asked why surgical care is not
      receiving recognition and support on the public health and global health agenda.
      Responses were categorized using the Shiffman framework on determinants of
      political priority for global initiatives by two independent investigators, and
      the number of responses for each of the 11 factors was calculated. RESULTS:
      Seventy-five Surgeons OverSeas members replied (75 of 176; 42.6% response rate).
      A total of 248 individual reasons were collected. The most common responses were
      related to external frame, defined as public portrayals of the issue (60 of 248;
      24.2%), and lack of effective interventions (48 of 248; 19.4%). Least cited
      reasons related to global governance structure (4 of 248; 2.4%) and policy window
      (4 of 248; 1.6%). CONCLUSIONS: This survey of a global surgery community
      identified a number of barriers to the recognition of surgical care on the global
      health agenda. Recommendations include improving the public portrayal of the
      problem; developing effective interventions and seeking strong and charismatic
      leadership.

PMID- 25940159
TI  - Postoperative pneumoperitoneum: is it normal or pathologic?
AB  - BACKGROUND: Pneumoperitoneum on computed tomography (CT) after abdominal surgery
      is common, but its incidence, duration, and clinical significance is widely
      debated. MATERIALS AND METHODS: A retrospective, cohort study of patients who
      underwent abdominal CT within 30 days of abdominal surgery. RESULTS: Among 344
      patients, pneumoperitoneum was found in 39% (135/344) of patients on
      postoperative days 0-6 in 53%, 7-13 in 41%, 14-20 in 23%, 21-27 in 13%, and 28-30
      in 0%. Pneumoperitoneum was associated with the presence of a drain (P = 0.014)
      but not with age, gender, body mass index, smoking history, lung disease, or open
      versus laparoscopic surgery (P > 0.05 for all variables). Eight patients required
      intervention (6%), most commonly for anastomotic leak (4 patients, 50%).
      CONCLUSIONS: Postoperative pneumoperitoneum on abdominal CT can be seen in up to
      23% of patients 3-weeks postoperatively; however, only 6% of the patients
      required intervention emphasizing the typically benign consequences of
      postoperative free air.

PMID- 25940160
TI  - Latissimus dorsi flap versus pedicled transverse rectus abdominis myocutaneous
      breast reconstruction: outcomes.
AB  - BACKGROUND: Pedicled breast reconstruction is a mainstay treatment for plastic
      surgeons. Although indications vary for each breast reconstruction technique,
      there exist some overlapping characteristics that may determine a successful
      outcome. We aimed to determine the impact flap selection has on postoperative
      outcomes and resource utilization. MATERIALS AND METHODS: Nationwide Inpatient
      Sample database (2010-2011) was reviewed for cases of latissimus dorsi (LD;
      International Classification of Diseases, Ninth Revision, Clinical Modification,
      85.71) and pedicled transverse rectus abdominis myocutaneous (pTRAM; 85.72)
      breast reconstruction. Males were excluded. Demographic, socioeconomic, clinical
      factors, postoperative complications, length of stay (LOS), and total charges
      (TC) were assessed. Chi-squared and multivariate analyses were performed to
      identify independent risk factors of resource utilization and postoperative
      complications. RESULTS: A total of 29,074 cases were identified; 17,670 (61%) LD
      and 11,405 (39%) pTRAM. 74% percent were Caucasian, 94% insured, and 66% were
      treated in teaching hospitals. There were 24 mortalities (15 LD, 9 pTRAM). LD
      patients were more likely to be obese (odds ratio [OR] = 1.3), suffer from flap
      loss (OR = 1.4), wound infection (OR = 1.6), wound dehiscence (OR = 2.2), and
      hematoma (OR = 1.3), P < 0.05. Patients undergoing pTRAM were more likely to
      undergo surgical revision (OR = 6.9), suffer from systemic infection (OR = 1.8),
      pneumonia (OR = 5.0), or pulmonary embolism (OR = 29.2), P < 0.05. Risk-adjusted
      multivariate analysis demonstrated LD was an independent risk factor for
      postoperative complication (OR = 1.4) and increased TC (OR = 1.3), P < 0.001.
      Conversely, undergoing pTRAM was an independent risk factor for increased LOS (OR
      = 6.3), P < 0.001. CONCLUSIONS: Analysis of a national database found LD breast
      reconstruction to have higher TC and increased risk for surgical site
      complications. Patients undergoing pTRAM had increased risk for pulmonary
      complications and LOS. Procedure selection may be refined as additional
      characteristics are discovered using outcomes-based research.

PMID- 25940161
TI  - The power of collaboration between surgery and engineering.

PMID- 25940162
TI  - Dietary and psych predictors of weight loss after gastric bypass.
AB  - BACKGROUND: Identifying severely obese patients who will succeed after bariatric
      surgery remains challenging. Although numerous studies have attempted to identify
      preoperative patient characteristics associated with weight loss, the roles of
      many dietary and psychological characteristics are unclear. The purpose of this
      study was to examine preoperative dietary and psychological predictors of
      successful weight loss after bariatric surgery. MATERIALS AND METHODS: This
      retrospective cohort study included all patients who underwent laparoscopic Roux
      en-Y gastric bypass from September 2011-June 2013 at a single institution (n =
      124). Patient demographics, comorbidities, dietary and psychological factors, and
      weight loss outcomes were extracted from the electronic medical record. Bivariate
      associations between these factors and successful weight loss (>=50% excess body
      weight) were examined. Factors significant at P <= 0.1 were included in a
      multivariate logistic regression model. RESULTS: On bivariate analysis, absence
      of either type 2 diabetes or hypertension, preoperative weight <270 lbs, no
      intentional past weight loss >50 lbs, no previous purging or family history of
      obesity, and no soda consumption preoperatively were associated with successful
      weight loss (P < 0.1). On multivariate analysis, successful weight loss was
      inversely associated with the presence of type 2 diabetes (odds ratio [OR], 0.22,
      95% confidence interval [CI], 0.06-0.73), maximum intentional past weight loss
      >50 lbs (OR, 0.12 [95% CI, 0.04-0.43]), and decreasing soda consumption by >50%
      (OR, 0.27 [95% CI, 0.08-0.99]). CONCLUSIONS: Patients with type 2 diabetes
      mellitus, significant previous weight loss, and poor soda consumption habits are
      more likely to experience suboptimal weight loss after bariatric surgery.
      Additional preoperative counseling and close postoperative follow-up is warranted
      for these patients.

PMID- 25940163
TI  - General surgical services at an urban teaching hospital in Mozambique.
AB  - BACKGROUND: As surgery becomes incorporated into global health programs, it will
      be critical for clinicians to take into account already existing surgical care
      systems within low-income countries. To inform future efforts to expand the local
      system and systems in comparable regions of the developing world, we aimed to
      describe current patterns of surgical care at a major urban teaching hospital in
      Mozambique. METHODS: We performed a retrospective review of all general surgery
      patients treated between August 2012 and August 2013 at the Hospital Central
      Maputo in Maputo, Mozambique. We reviewed emergency and elective surgical
      logbooks, inpatient discharge records, and death records to report case volume,
      disease etiology, and mortality. RESULTS: There were 1598 operations (910
      emergency and 688 elective) and 2606 patient discharges during our study period.
      The most common emergent surgeries were for nontrauma laparotomy (22%) followed
      by all trauma procedures (18%), whereas the most common elective surgery was
      hernia repair (31%). The majority of lower extremity amputations were above knee
      (69%). The most common diagnostic categories for inpatients were infectious
      (31%), trauma (18%), hernia (12%), neoplasm (10%), and appendicitis (5%). The
      mortality rate was 5.6% (146 deaths), approximately half of which were related to
      sepsis. CONCLUSIONS: Our data demonstrate the general surgery caseload of a
      large, academic, urban training and referral center in Mozambique. We describe
      resource limitations that impact operative capacity, trauma care, and management
      of amputations and cancer. These findings highlight challenges that are
      applicable to a broad range of global surgery efforts.

PMID- 25940164
TI  - Detection and molecular characterisation of Grapevine Syrah virus-1 isolates from
      Central Europe.
AB  - Grapevine Syrah virus-1 (GSyV-1) was identified by small-RNA deep sequencing in
      Slovak grapevine co-infected by several other viruses. The RT-PCR assays
      developed in this work substantially improved the virus detection and allowed the
      identification of GSyV-1 in tested grapevine samples from Slovakia and the Czech
      Republic at an unexpectedly high rate (ca. 30 %). Subsequently, complete genome
      sequences of 3 GSyV-1 isolates (2 Slovak and 1 Czech) were determined by Sanger
      sequencing, showing a typical marafivirus genome organization. Analyses of
      complete genome sequences showed a higher intra-group diversity among these 3
      central European GSyV-1 isolates (differences reaching 7.1 % at the nucleotide
      level) in comparison to 3 previously characterized North American isolates (only
      1.2 % intra-group divergence). A substantially higher divergence among central
      European isolates and their clustering into two major phylogenetic groups was
      further confirmed by the partial genome analysis of additional 26 isolates. The
      CP-centered study did not support the geography-based clustering among central
      European and American isolates. Nevertheless, the sequence data of the highly
      variable 5'-proximal portion of the genome obtained for few additional isolates
      from Slovakia and Czech Republic showed the presence of both, "European-" and
      "north American-like", GSyV-1 isolates in the analyzed grapevine samples.

PMID- 25940165
TI  - [Surgical principles of gastrointestinal stromal tumors at different locations].
AB  - Gastrointestinal stromal tumors(GIST) are the most common mesenchymal tumors in
      gastrointestinal tract. At present, surgical and molecular targeted therapies are
      the main treatments. Operation is properly the only way of radical resection. The
      general principles of surgery are complete resection of the tumor, negative
      margins, as well as no intraoperative tumor rupture. The choice of surgical
      skills for GIST is obviously affected by different locations. This paper reviews
      current literatures combined with our experiences, and elaborates relevant
      contents in detail. 

PMID- 25940166
TI  - [Application of gene mutation detection in gastrointestinal stromal tumors].
AB  - Gastrointestinal stromal tumors(GISTs) are the most common gastrointestinal
      mesenchymal tumors of the gastrointestinal tract. Most of GISTs are characterized
      by mutation in the c-kit or PDGFR-alpha genes. In recent years, detection of gene
      mutation in GISTs has been widely used. In addition to the contribution to the
      diagnosis of difficult cases, such detection also has important value in
      predicting the efficacy of therapeutic drugs targeting, guiding clinical
      treatment and evaluating the prognosis of patients. In a word, gene mutation
      detection should be considered as the important standard for exact diagnosis and
      treatment of GISTs. 

PMID- 25940167
TI  - [Re-appraisal of risk assessment schemes in gastrointestinal stromal tumors].
AB  - The biological behavior of gastrointestinal stromal tumor(GIST) is highly
      variable. To assess the risk of recurrence of the primary tumor accurately is a
      key challenge. The risk assessment system of GIST has experienced several
      revolutions. The present accepted risk stratification scheme is still to be
      consummated. The pathological morphological characteristics, mutational features,
      and other biomarkers are helpful to improve the risk assessment system. The risk
      assessment of GIST in the future will be more and more diversified. 

PMID- 25940168
TI  - [Neoadjuvant therapy of imatinib in gastrointestinal stromal tumors and the
      timing of surgery].
AB  - Imatinib is the key medication for adjuvant therapy in gastrointestinal stromal
      tumors(GIST) and the first line therapy for patients with metastatic or recurrent
      GIST. Preoperative treatment with imatinib may improve R0 resection rate and
      provide the chance of metastasectomy for cytoreduction as well as prolonging
      patient's survival. We investigate the significance of neoadjuvant therapy of
      imatinib and the timing of surgery by reviewing clinical trials and consensus in
      recent years. 

PMID- 25940169
TI  - [Diagnosis and treatment of duodenal gastrointestinal stromal tumors].
AB  - In order to promote clinical capability on duodenal gastrointestinal stromal
      tumor(GIST), literature review and experience summary were documented in this
      paper. Duodenal GIST is not rare in clinical practice. With the similar
      pathologic conditions, GIST in duodenum present a higher malignant risk than that
      in stomach. The cases who would receive imatinib mesylate as preoperative therapy
      require a precise preoperative diagnosis obtained by endoscopic ultrasound and
      fine needle aspiration cytology. Therapeutic strategy should be based on surgical
      R0 resection with clear margins, preserving pancreatic function and avoiding
      adjacent organs resection when possible. Limited resection is appropriate and
      results in similar oncological outcome compared with extensive procedure in
      suitable cases. 

PMID- 25940170
TI  - [Diagnosis and treatment for complicated gastrointestinal stromal tumors].
AB  - Tyrosine kinase inhibitor(TKI) combined with surgical treatment is the optimal
      strategy for gastrointestinal stromal tumors(GIST). However, there is no systemic
      report about the complicated GIST(recurrence or metastasis, peritoneal
      dissemination, combined resection of multiple organs), except the cases review
      and experimental studies. Tyrosine kinase inhibitor combined with surgery may
      increase the overall survival of complicated GIST. This article will describe the
      definition, clinical features, surgical and drug therapy, and prognosis, in order
      to provide reliable theoretical basis and experience for clinical doctors,
      prolong patient survival and improve the quality of survival. 

PMID- 25940171
TI  - [Clinical management of advanced gastrointestinal stromal tumors after failure of
      at least both imatinib and sunitinib targeted therapy].
AB  - The emergence of small molecular tyrosine kinase inhibitors opened the era of
      targeted therapy of gastrointestinal stromal tumor(GIST). Survival and life of
      quality of patients from advanced stage are significantly improved by using
      targeted therapy. However, with prolonged treatment, drug resistance is becoming
      more and more common and directly affects the survival of patients. The current
      clinical management in failure of multi-line targeted therapies will be discussed
      in this article. 

PMID- 25940172
TI  - [Evaluation and endoscopic treatment of small and micro gastrointestinal stromal
      tumors].
AB  - The incidence of small and micro gastrointestinal stromal tumors is increasing
      significantly because of the enhanced health consciousness and advanced
      endoscopic technology. But there still is controversial in the biological
      behavior and clinical treatment of GIST. The treatment of the GIST with
      endoscopic technology has obvious advantages. This method can remove tumor and
      avoid significant trauma. In this paper, the biological behavior, clinical
      evaluation and endoscopic treatment of the GIST are discussed. 

PMID- 25940173
TI  - [Mutation profiles of c-kit/PDGFRalpha and its associations with
      clinicopathological characteristics in Chinese gastrointestinal stromal tumors:
      analysis of 827 cases].
AB  - OBJECTIVE: To elucidate the mutation profiles of c-kit/PDGFRalpha and its
      associations with clinicopathological characteristics in large scale Chinese
      gastrointestinal stromal tumors(GISTs). METHODS: Clinicopathological data and
      tumor samples of 1002 GIST patients treated in the Peking University Cancer
      Hospital from September 2002 to January 2014 were retrospectively collected.
      Mutation status of c-kit(exons 9, 11, 13, and 17) and PDGFRalpha(exons 12 and 18)
      genes were detected by direct sequencing. Association between mutation profiles
      and clinicopathological features of mutant patients were statistically analyzed.
      RESULTS: Among all the 827 mutant patients, c-kit and PDGFRalpha mutations were
      found in 798 cases(96.5%, exons 11, 9, 13, and 17 mutations in 669, 99, 18, 12)
      and 29 cases (3.5%, exons 12 and 18 in 2 and 27), respectively. As for c-kit
      gene, deletion mutation was most frequent in exon 11(n=325), and then point
      mutation(n=172), mixed mutation(n=135), and duplication mutation(n=37). The
      duplication of codons 502-503 was the unique genotype for exon 9 of c-kit gene,
      and point mutation was the single mutation type for exons 13 and 17 of c-kit
      gene. Point mutation was the most common mutation for PDGFRalpha gene with few
      deletion or mixed mutations. Most deletion mutations of c-kit gene were located
      in 5' region of exon 11, duplication mutations were mainly located in 3' region
      of exon 11, and point mutations were focused on codons 556-560. Mutation type of
      exon 11 was associated with age, gender, primary location, tumor size,
      karyokinesis image and CD 34 expression(all P<0.05). CONCLUSION: GISTs are
      featured by frequent gene mutations, many mutation types, and specificity for
      mutations in same exons or different exons.

PMID- 25940174
TI  - [Clinicopathological features of small gastrointestinal stromal tumors].
AB  - OBJECTIVE: To investigate the clinicopathological features of small
      gastrointestinal stromal tumors(GISTs) and to evaluate the efficacy of endoscopic
      therapy for GISTs. METHODS: Clinicopathological and follow-up data of 418
      patients with GISTs undergoing endoscopic therapy in the Zhongshan Hospital
      between January 2009 and July 2014 were analyzed retrospectively. All the cases
      were evaluated by the NIH risk classification and AIFP classification, and were
      grouped according to the tumor size and location. Nuclear atypia and mitotic
      count were used to evaluate the biological behavior of small GIST. Efficacy of
      endoscopic therapy was analyzed with follow-up data. RESULTS: Out of 418
      patients, GISTs located in the esophagus was 14(3.3%), in the stomach 389(93.1%),
      in the duodenum 5(1.2%), in the rectum 10(2.4%). A total of 412(98.6%) patients
      were mainly spindle cells, and mitosis was not found in 320(76.5%) patients. In
      389 small stomach GIST, 245(58.6%) were in fundic region. Cases were divided into
      four groups according to the size and the result revealed the bigger the size,
      the more the mitotic count. Nuclear atypia in the 1.5-1.9 cm group was
      significantly higher compared to other groups. Cases were divided into four
      groups according to the location and the result revealed the mitotic count was
      not associated to the location. While the nuclear atypia of stomach GIST was
      significantly higher than that of esophageal GIST and the nuclear atypia of
      rectum GIST was significantly higher than that of other positions. The median
      follow-up was 32(4-69) months. One case(gastric fundus GIST, >1.5 cm) presented
      local recurrence 23 months after operation and underwent endoscopic resection
      again. No recurrence or metastasis was found in other patients. CONCLUSIONS:
      Endoscopic resection technique is effective for small GISTs patients. The small
      GISTs with 0.4 cm diameter or less are often benign and should be followed up for
      long time. The small GISTs with 0.5 cm diameter or more possess the risk of
      malignancy, then surgical resection should be performed. Rectum small GISTs
      (except for 0.4 cm diameter or less) have worse biological behavior and should be
      removed.

PMID- 25940175
TI  - [Analysis of clinicopathological characteristics in 180 patients with wild type
      gastrointestinal stromal tumors].
AB  - OBJECTIVE: To investigate the clinicopathological characteristics of 180 patients
      with wild type gastrointestinal stromal tumors(GIST). METHODS: The
      clinicopathological data of 180 patients with wild type GIST treated in the
      Peking University Cancer Hospital between October 2001 and September 2013 were
      analyzed and compared to 513 mutant patients. RESULTS: 180 patients were included
      in this study, and the median age 52.5 years(16-78 years). The percentage of
      female was significantly higher than that of male among patients under the age of
      40. Primary tumor sites mainly included stomach(45.6%) and small
      intestine(23.9%). The positive expression of CD117, DOG-1, and CD34 were 81.6%,
      75.6%, and 74.7%, respectively, which were highest in stamach, secondly in small
      intestine. The percentage of tumor with length >5 cm was higher in patients under
      the age of 50 compared to patients more than 50 years, and a significant
      correlation was found between tumor size and mitosis. Compared to mutant
      patients, wild type patients had the following features: younger, primary tumor
      site of stomach, tumor length <= 2 cm, and the lower positive expression of CD117
      and DOG-1. CONCLUSIONS: The significant differences in primary tumor sites, tumor
      size, and the positive expression of CD117/DOG-1 were found between wild type
      GIST and mutant GIST, which suggested that wild type GIST might be an independent
      subgroup to be concerned in clinical practice.

PMID- 25940176
TI  - [Clinical analysis of 36 cases of duodenal gastrointestinal stromal tumors].
AB  - OBJECTIVE: To review the clinical features of duodenal gastrointestinal stromal
      tumors(GISTs), and to compare the clinical efficacy among different surgical
      treatments for duodenal GISTs. METHODS: Clinicalpathological data of 36 cases of
      duodenal GISTs undergoing operation in The First Affiliated Hospital of Sun Yat
      sen University from January 2000 to July 2013 were retrospectively analyzed. All
      the patients received surgical treatments, including 15 cases with regional
      resection, 8 cases with segmental resection, 12 cases with
      pancreaticoduodenectomy (PD), and 1 case with liver biopsy, respectively.
      Clinical efficacy between pancreaticoduodenectomy (PD) and non-PD (NPD) was
      compared. RESULTS: Nine of 36 cases (25%) developed postoperative complications
      who were all in the PD group. Eight patients recovered and healed finally after
      active treatment, and 1 case was complicated with acute pancreatitis, pancreatic
      fistula and intra-abdominal infection. The median follow-up time was 54 months
      and the 5-year overall survival (OS) rate and 5-year recurrence-free survival
      (RFS) rate were 78.1% and 72.1%, respectively. The 5-year OS rate in the PD group
      and the NPD group was 61.1% and 61.1% respectively. The 5-year RFS rate in the PD
      group and the NPD group was 85.8% and 78.8% respectively. Statistical analysis
      showed no significant difference between the both groups (P=0.71 and P=0.89).
      CONCLUSIONS: For duodenal GISTs patients, regional resection and segmental
      resection have similar clinical outcomes to pancreaticoduodenectomy while the
      former two can obviously decrease the incidence of postoperative complications.
      Based on the premise of R0 resection guaranteed, regional sectional and segmental
      resection with less injury should be the surgical treatment of choice.

PMID- 25940177
TI  - [Comparative study of clinical efficacy between abdominoperineal resection and
      anterior resection procedure in patients with rectal cancer].
AB  - OBJECTIVE: To compare clinical efficacy between abdominoperineal resection (APR)
      procedure and anterior resection(AR) procedure in patients with rectal cancer.
      METHODS: Clinicopathological data of 309 cases with rectal cancer undergoing
      resection in Peking University People's Hospital from January 1998 to December
      2012 were retrospectively analyzed. Short-term outcomes, local recurrence,
      overall survival (OS) and progression-free survival (PFS) were investigated
      between two groups. RESULTS: As compared to the AR group, the operative time was
      longer [(268.5 +/- 66.7) min vs. (247.4 +/- 64.2) min, P=0.005], blood
      loss[(668.5 +/- 680.1) ml vs.(441.8 +/- 478.6) ml, P=0.001] and drainage volume
      were more[(66.9 +/- 54.7) ml vs. (49.0 +/- 45.9) ml, P=0.002] in the APR group.
      There was no significant difference of local recurrence between the two groups,
      while the 5-year local recurrence rate of T3-T4 patients undergoing APR procedure
      (24.9%) was higher than that of AR group (13.9%)(P=0.038), especially in the
      patients with tumors located at 4-6 cm away from the anus verge. There were no
      significant differences of OS (P=0.273) and PFS (P=0.589) between two groups,
      while both 5-year OS and PFS of T3-T4 patients with BMI >= 24 undergoing APR
      procedure (43.1% and 42.8%) were significantly worse than those of patients
      undergoing AR procedure (87.9% and 76.9%, P=0.022 and P=0.041). CONCLUSIONS: The
      overall prognosis of patients after APR and AR is comparable. Tumor located at 4
      6 cm away from the anus verge, T3-T4 stage, obese may play an important role in
      the worse prognosis of the patients undergoing APR procedure.

PMID- 25940178
TI  - [Clinical application of artificial anal reconstruction after laparoscopic
      abdominoperineal resection in low rectal cancer patients].
AB  - OBJECTIVE: To assess the outcome and quality of life artificial anal
      reconstruction after laparoscopic abdominoperineal resection(APR) in low rectal
      cancer patients. METHODS: Clinical data of 60 cases with low rectal cancer
      undergoing APR in our department from January 2010 to January 2013 were
      retrospectively analyzed. Sixty patients were divided into 2 groups according to
      anal reconstruction procedure, inclding 32 patients of abdominal colostomy as
      colostomy group and 28 patients of in-situ artificial anal reconstruction as anal
      reconstruction group. After a median follow-up of 1 year, the quality of life was
      assessed by Fetal Incontinence Quality of Life Scale(FIQL scale) and Cleveland
      Clinic Florida Fecal Incontinence Scores(CCS-FIS scale). In addition, the outcome
      and complications were compared between the two groups. RESULTS: Compared with
      the colostomy group, the anal reconstruction group presented longer operation
      time [(204.8 +/- 18.8) min vs. (173.3 +/- 23.5) min, P<0.01], later passage time
      [(45.1 +/- 9.3) h vs. (27.7 +/- 9.4) h, P<0.01], and higher incidence of mucosal
      edema(42.9% vs. 18.8%, P<0.05). There were no significant differences in average
      hospital stay and other complication morbidities(all P>0.05). After follow-up,
      the embarrassment scale in anal reconstruction group was better compared to
      colostomy group(3.1 vs. 2.2, P<0.01). However, there were no significant
      differences in the lifestyle, coping and depression scales between the two groups
      (all P>0.05). Twenty(71.4%) patients in anal reconstruction group had
      satisfactory continence 1 year after operation. CONCLUSION: In-situ artificial
      anal reconstruction after laparoscopic abdominoperineal resection can preserve
      fecal function in low rectal cancer patients and improve the quality of life
      after APR operation.

PMID- 25940179
TI  - [Transsphincteric approach for rectovaginal fistulas repair].
AB  - OBJECTIVE: To investigate the safety and feasibility of the posterior
      transsphincteric approach for rectovaginal fistulas repair. METHOD: Data of 23
      cases of rectovaginal fistulas treated by the transsphincteric approach in the
      Peking Union Medical College Hospital, from April 1994 to May 2014 were reviewed.
      The success rate of this surgical procedure and the postoperative complications
      were analyzed. RESULTS: The procedure of the transsphincteric approach for the
      repair of rectovaginal fistulas was performed successfully in all 23 cases. Three
      patients(13%) suffered surgical wound infection, which healed after regular
      dressing changes. In 19 cases, the fistulas were successfully repaired with an
      initial healing rate of 82.6%. The surgical repair failed to accomplish initial
      healing in 3 cases(13%). No complications including rectocutaneous fistula or
      anal sphincter malfunction occurred in these patients. CONCLUSION: The
      transsphincteric approach for the repair of rectovaginal fistulas is a safe and
      feasible procedure with a good success rate.

PMID- 25940180
TI  - [Relationship between CD4+CD25(High)CD127(low) regularly T cells in the
      peripheral blood and tumor regression after neoadjuvant therapy in patients with
      rectal cancer].
AB  - OBJECTIVE: To observe the proportion change of immune cells in the peripheral
      blood of patients with rectal cancer after neoadjuvant therapy and to explore the
      relationship between tumor regression and CD4+CD25(High)CD127(low) regularly T
      cells(Treg cells). METHODS: Patients with rectal cancer who underwent the
      neoadjuvant therapy before surgery at the Shanxi Cancer Hospital Colorectal
      Surgery Department from January to December 2013 were prospectively enrolled.
      These patients were divided into down-staging group and non-down-staging group
      according to the change of staging in accordance with TNM classification for
      rectal cancer after neoadjuvant therapy. Flow cytometry was used to analyze the
      proportions of Treg cells, CD4+T cells, CD8+T cells, NK cells, B cells, and
      CD4+/CD8+ ratio in the peripheral blood from these patients before and after
      neoadjuvant therapy. RESULTS: A total of 108 patients were enrolled, including 76
      cases in the down staging group and 32 cases in the non-down-staging group.
      Differences of immune cells proportions between two groups before neoadjuvant
      therapy were not statistically significant(all P>0.05). In the down-staging
      group, the proportions of Treg cells, B cells and CD4+/CD8+ ratio were decreased
      while the proportion of NK cells did not change obviously after the neoadjuvant
      therapy. Interestingly, in the non-down-staging group, the proportions of B cells
      and CD4+/CD8+ ratio were decreased while the proportions of Treg cells and NK
      cells did not change obviously after the neoadjuvant therapy. In addition, after
      neoadjunvat therapy, the proportion of Treg cells in down-staging group was
      significantly lower than that in non-down-staging group [(4.4 +/- 1.7)% vs. (6.2
      +/- 1.9)%, P=0.001]. CONCLUSION: For patients in the down-staging group after
      neoadjuvant therapy, the proportion of Treg cells in peripheral blood decreases,
      suggesting that Treg cells may be a valuable biomarker for assessing tumor
      regression.

PMID- 25940181
TI  - [Association of microRNA101 expression with clinicopathologic features and
      prognosis in colorectal cancer].
AB  - OBJECTIVE: To investigate the microRNA101(miR101) expression and its clinical
      significance in colorectal cancer. METHODS: Tissue microarrays containing 56
      specimens of normal mucosa, 51 adenoma and 735 colorectal cancer were examined by
      locked nucleic acid in-situ hybridization(LNA-ISH) for miR101 expression.
      Relationship between miR101 expression and clinicopathologic parameters and
      prognosis of colorectal cancer patients were analyzed. Fresh frozen tissues
      containing 5 specimens of normal mucosa, 5 adenoma and 47 colorectal cancer were
      examined by RT-PCR to verify the accuracy of LNA-ISH. RESULTS: Expression of
      miR101 increased gradually from normal mucosa, adenoma to stage I colorectal
      cancer (all P<0.01), and decreased gradually from stage II(, stage III( to stage
      IIII( colorectal cancer (all P<0.01). Overexpression of miR101 was related with
      lower incidence of lymph node metastasis, lower metastasis rate, higher
      differentiation and lower recurrence rate (all P<0.01). Multivariate survival
      analysis demonstrated that miR101 expression was an independent prognostic factor
      of overall survival (HR=0.550, 95% CI: 0.351-0.863) and disease free
      survival(HR=0.562, 95% CI: 0.397-0.794) in colorectal cancer patients.
      Overexpression of miR101 predicted a better prognosis in colorectal cancer
      patients. CONCLUSIONS: Expression of miR101 is associated with the genesis and
      development of colorectal cancer, and may serve as an independent prognostic
      factor for colorectal cancer patients.

PMID- 25940182
TI  - [Co-inhibition effect of 17-DMAG and oxaliplatin on proliferation and invasion of
      colorectal cancer cells].
AB  - OBJECTIVE: To explore the effect of heat shock protein 90 (HSP90) inhibitor (17
      DMAG) and oxaliplatin on the proliferation and invasion of colorectal cancer.
      METHODS: After 17-DMAG, oxaliplatin and half-dose combination of 2 drugs
      processing colorectal cancer SW480 and HCT116 cell lines, CCK8 assay was applied
      to detect cell viability. RT-PCR and Western blot were used to detect the
      expression level of the apoptosis-related molecules. Transwell chemokine axis
      experiment and Western blot were employed to detect cell invasion ability and the
      expression level of tumor metastasis-associated protein. RESULTS: The growth of
      SW480 and HCT116 cells was inhibited after the administration of 17-DMAG and
      oxaliplatin(P<0.05) in dose- and time-dependent manner. Processed by 17-DMAG 100
      nmol/L, oxaliplatin 50 mg/L and half-dose combination of 2 drugs, transcription
      level of the apoptosis inhibitory gene (Bcl-2) in SW480 and HCT116 cells was
      decreased, the level of apoptosis promoting gene (Bax) transcription and protein
      PARP-1 spliceosome expression was increased, and the above trend was more obvious
      when using half-dose combination of 2 drugs. Transwell chemokine axis experiments
      showed the penetrating relative percentage and expression level of MMP9 and
      integrin beta3 decreased, especially for half-dose combination of 2 drugs.
      CONCLUSION: 17-DMAG and oxaliplatin can co-inhibit the proliferation and invasion
      of colorectal cancer.

PMID- 25940183
TI  - [Relationship between NMDA receptor and postoperative fatigue syndrome and its
      associated central mechanism].
AB  - OBJECTIVE: To explore the central mechanism of postoperative fatigue syndrome by
      detecting the expression of NMDA receptor and tryptophan metabolism. METHODS:
      After being numbered according to the weight, ninety-six male SD rats were
      randomly divided into control group (bowel loop was flipped after laparotomy and
      received intraperitoneal injection of saline at a dose of 1 ml/kg), POFS
      model(70% of the length of small intestine was resected and received
      intraperitoneal injection of saline at a dose of 1 ml/kg), and NMDA antagonist
      groups(70% of the length of small intestine was resected and received
      intraperitoneal injection of MK801 at a dose of 1 ml/kg). Each group was divided
      into subgroups by postoperative 1, 3, 5 and 7 d, with 8 rats in each subgroup.
      The hippocampus was removed at each time point after open field test (OFT) to
      detect the mRNA expression levels of NMDA receptor 1 and kynurenine
      aminotransferase III((KATIII() by real-time PCR. Protein level of NMDA receptor 1
      was detected by Western blot. High performance liquid chromatography (HPLC) was
      used to measure the concentrations of tryptophan (TRP), kynurenine (KYN) and
      kynurenic acid(KYNA). Ultra-structural changes of hippocampal neurons were
      observed by transmission electron microscopy(TEM). RESULTS: As compared to
      control group, exercise score decreased(P<0.05), rest time and central panel
      residence time prolonged, periphery/central panel ratio increased (all P<0.05),
      mRNA and protein expressions of NMDA receptor 1 increased (P<0.05), mRNA
      expression of KAT III( decreased (P<0.05), KYN/TRP ratio and KYN/KYNA ratio
      decreased (all P<0.05) in POFS group on postoperative day 1 and 3. As compared to
      POFS group, central panel residence time and periphery/central panel ratio
      decreased on postoperative day 1, and mRNA and protein expressions of NMDA
      receptor 1 decreased on postoperative day 1 and 3 (all P<0.05) in antagonist
      group. TEM revealed that degenerated neuron was found in the hippocampus of POFS
      rats, while such damage was improved in antagonist group. CONCLUSION: The
      increased expression level of NMDA receptor may play an important role in POFS.
      NMDA receptor antagonist MK801 may improve the POFS.

PMID- 25940184
TI  - [Effect of intestinal resection on hydrogen sulfide biosynthesis and the damage
      of Cajal interstitial cells].
AB  - OBJECTIVE: To investigate the effect of intestinal resection on hydrogen sulfide
      (H2S) biosynthesis and interstitial cells of Cajal(ICC) in mice. METHODS: After
      intestinal resection mouse model was established, the activity of MPO in the
      proximal anastomosis intestinal tissue were detected. Sensitive sulphur electrode
      assay was applied to measure the H2S level. RT-PCR technique was employed to
      investigate the mRNA expression of the endogenous H2S biosynthesis enzymes,
      cystathionine-b-synthase (CBS) and cystathionine-c-lyase (CSE).
      Immunofluorescence staining was used to detect the expression of c-kit in order
      to calculate the area of ICC. RESULTS: The mRNA expression of CSE was detected in
      the small intestine tissue of mice, while no CBS mRNA was found. The mRNA
      expression of CSE in proximal anastomotic stoma increased in time-dependent
      manner in the model group. CSE mRNA expression began to increase 1 hour after
      operation, reached the peak at 6th hour, then decreased gradually, and was
      similar to the control group at postoperative 24th hour. Compared to the model
      group, in the intestinal tissues of proximal 3 cm to anastomotic stoma, the mRNA
      expression of CSE (1.16 +/- 0.18 vs. 1.63 +/- 0.13, P<0.05), the activity of MPO
      [(0.54 +/- 0.07) U/g vs. (0.83 +/- 0.09) U/g, P<0.05], the H2S level [(36.1 +/-
      6.1) nmol/mg vs. (5.3 +/- 5.6) nmol/mg, P<0.05] were significantly reduced in the
      PPG group. Meanwhile, average percentage of positive ICC area in the PPG groups
      was significantly higher [(2.26 +/- 0.19)% vs. (1.65 +/- 0.24)%, P<0.05].
      CONCLUSIONS: Inflammatory reaction in muscular layer induced by intestinal
      resection up-regulates the mRNA expression of CSE proximal to anastomotic stoma,
      generates excess H2S to damage ICC leading to intestinal motor dysfunction.
      Preoperative inhibition of endogenous H2S generation may protect the ICC.

PMID- 25940185
TI  - [Current status and progress of medical imaging in diagnosis of gastrointestinal
      stromal tumors].
AB  - Gastrointestinal stromal tumors (GISTs) are derived from non-directed
      differentiation of gastrointestinal mesenchymal tissue, which lack of typical
      clinical symptoms, and many asymptomatic GISTs are often found on physical
      examination. The tumor is primarily through implantation metastasis and blood
      metastasis. Currently, conventional medical imaging methods, such as X-ray barium
      meal, US, CT, MRI, PET/CT and ES, are still the main means of diagnosis of GISTs.
      Early diagnosis and early treatment are key factors of the prognosis in GISTs.
      Therefore, we need to be proficient in various medical imaging methods, then
      apply them to the diagnosis of GISTs, and to provide comprehensive and valuable
      information for clinical practice. Through retrieving and consulting literature
      of medical imaging associated with GISTs, this paper reviews the current status
      and progress of medical imaging in diagnosis of GISTs.

PMID- 25940186
TI  - [Advances in diagnosis and treatment of intestinal Behcet's disease].
AB  - Behcet's disease (BD) affects gastrointestinal tract is defined as intestinal BD.
      The diagnosis and therapeutic efficacy of intestinal BD are still lack of
      specific diagnostic method and effective treatment. Intestinal BD is diagnosed
      according to established criteria based on colonoscopic features and biopsy. To
      date, 5-aminosalicylic acid and systemic corticosteroids are established as the
      first-line therapy, while immunosuppressants and infliximab are used as second
      line therapy for patients with glucocorticoid resistant. In the process of
      therapy, we need to carefully evaluate the patient's condition and be cautious
      about surgical treatment. Surgical intervention should only be considered in
      patients with serious complications. In this review, we summarize the recent
      advances in diagnosis, disease activity index and treatment of intestinal BD, and
      provide the theoretic proofs to clinical application.

PMID- 25940187
TI  - Is frozen section analysis of ureteral margins at time of radical cystectomy
      useful?
AB  - The clinical utility of intraoperative frozen section analysis (FSA) of ureters
      at the time of radical cystectomy (RC) for urothelial cancer (UC) remains
      controversial and subject to considerable debate. Potential advantages include
      intraoperative detection of carcinoma in situ (CIS) or overt malignancy and
      directed ureteral sectioning to achieve negative margins to reduce anastomotic
      recurrence. The information gained at the time of FSA may be useful for risk
      adapted upper tract surveillance. To critically assess the utility of FSA with
      respect to these potential advantages, we review the operating characteristics of
      FSA as a diagnostic test, the relationship between upper tract urothelial
      carcinoma (UTUC) recurrence and abnormal FSA, and the overall evidence for FSA on
      oncological end points and cost-effectiveness. Taken together, the weight of
      evidence suggests that while FSA is a reasonable diagnostic test, its utility has
      been recently questioned, and prospective study is warranted. There is a need to
      quantify the risk reduction in anastomotic recurrence in light of the cost
      effectiveness of FSA compared to the alternative of only performing permanent
      analysis of proximal ureteral margins. Given the low rates of UTUC recurrence
      reported in the literature, the weak association between FSA and these
      recurrences, and mortality in retrospective studies, the clinical impact of
      reducing UTUC recurrence by FSA must continue to be critically evaluated. 

PMID- 25940188
TI  - Sox2 Deacetylation by Sirt1 Is Involved in Mouse Somatic Reprogramming.
AB  - Mouse somatic cells can be reprogrammed into induced pluripotent stem cells by
      defined factors known to regulate pluripotency, including Oct4, Sox2, Klf4, and c
      Myc. Together with Oct4, Sox2 plays a major role as a master endogenous
      pluripotent genes trigger in reprogramming. It has been reported that Sirtuin 1
      (Sirt1), a member of the Sirtuin family of NAD(+) -dependent protein
      deacetylases, is involved in embryonic stem cell antioxidation, differentiation,
      and individual development. However, as a deacetylation enzyme, whether Sirt1
      influences reprogramming through its post-translational modification function
      remains unknown. In this study, we provide evidence that deacetylation of Sox2 by
      Sirt1 is required for reprogramming. We found that a low level of Sox2
      acetylation could significantly increase reprogramming efficiency. Furthermore,
      we found that Sox2 can be deacetylated by Sirt1 in an Oct4-mediated manner.
      Compared with wild-type cells, Sirt1-null mouse embryonic fibroblasts exhibit
      decreased reprogramming efficiency, and overexpression of Sirt1 rescues this
      defect. In addition, Sirt1 functions in the regulation of reprogramming through
      deacetylating Sox2. Taken together, we have identified a new regulatory role of
      Sirt1 in reprogramming and provided a link between deacetylation events and
      somatic cell reprogramming. Stem Cells 2015;33:2135-2147. 

PMID- 25940190
TI  - A triple-color fluorescent probe for multiple nuclease assays.
AB  - We develop a triple-color fluorescent probe which may function as a lab-on-a-DNA
      molecule for simultaneous detection of multiple exonucleases/restriction
      endonucleases. This triple-color fluorescent probe can be further applied for the
      discrimination of seven exonucleases and four cell lines as well as the screening
      of various nuclease inhibitors. 

PMID- 25940189
TI  - How China's new health reform influences village doctors' income structure:
      evidence from a qualitative study in six counties in China.
AB  - BACKGROUND: In 2009, health-care reform was launched to achieve universal health
      coverage in China. A good understanding of how China's health reforms are
      influencing village doctors' income structure will assist authorities to adjust
      related polices and ensure that village doctors employment conditions enable them
      to remain motivated and productive. This study aimed to investigate the village
      doctors' income structure and analyse how these health policies influenced it.
      METHODS: Based on a review of the previous literature and qualitative study,
      village doctors' income structure was depicted and analysed. A qualitative study
      was conducted in six counties of six provinces in China from August 2013 to
      January 2014. Forty-nine village doctors participated in in-depth interviews
      designed to document their income structure and its influencing factors. The
      themes and subthemes of key factors influencing village doctors' income structure
      were analysed and determined by a thematic analysis approach and group
      discussion. RESULTS: Several policies launched during China's 2009 health-care
      reform had major impact on village doctors. The National Essential Medicines
      System cancelled drug mark-ups, removing their primary source of income. The
      government implemented a series of measures to compensate, including paying them
      to implement public health activities and provide services covered by social
      health insurance, but these have also changed the village doctors' role.
      Moreover, integrated management of village doctors' activities by township-level
      staff has reduced their independence, and different counties' economic status and
      health reform processes have also led to inconsistencies in village doctors'
      payment. These changes have dramatically reduced village doctors' income and
      employment satisfaction. CONCLUSIONS: The health-care reform policies have had
      lasting impacts on village doctors' income structure since the policies'
      implementation in 2009. The village doctors have to rely on the salaries and
      subsidies from the government after the drug mark-up was cancelled. China's
      national health reforms are attempting to draw village doctors into the national
      health workforce, but the policies have impacted their income and independence.
      Further research into these concerns and monitoring of measures to adequately
      compensate village doctors should be undertaken. Reasonable compensation
      strategies should be established, and sufficient subsidies should be allocated in
      a timely manner.

PMID- 25940191
TI  - Genetic diversity of Venezuelan alphaviruses and circulation of a Venezuelan
      equine encephalitis virus subtype IAB strain during an interepizootic period.
AB  - Several species of alphaviruses have been previously described in the Americas,
      some of which are associated with encephalitis and others are associated with
      arthralgia. Venezuelan equine encephalitis virus (VEEV) and eastern equine
      encephalitis virus (EEEV) are endemic to Venezuela, with the former being
      responsible for major outbreaks of severe and often fatal disease in animals and
      humans. The aim of this study was to analyze the genetic diversity of Venezuelan
      alphaviruses isolated during two decades (1973-1999) of surveillance in northern
      Venezuela. Phylogenetic analysis indicated the circulation of a VEEV subtype IAB
      strain 8 years after the last reported outbreak. Thirteen strains within two
      subclades of South American lineage III of EEEV were also found in Venezuela.
      Considerable genetic variability was observed among Venezuelan Una virus strains,
      which were widely distributed among the clades. The first Venezuelan Mayaro
      sequence was also characterized. 

PMID- 25940192
TI  - Description of leprosy classification at baseline among patients enrolled at the
      uniform multidrug therapy clinical trial for leprosy patients in Brazil.
AB  - The uniform multidrug therapy clinical trial, Brazil (U-MDT/CT-BR), database was
      used to describe and report the performance of available tools to classify 830
      leprosy patients as paucibacillary (PB) and multibacillary (MB) at baseline. In a
      modified Ridley and Jopling (R&J) classification, considering clinical features,
      histopathological results of skin biopsies and the slit-skin smear bacterial load
      results were used as the gold standard method for classification. Anti-phenolic
      glycolipid-I (PGL-I) serology by ML Flow test, the slit skin smear bacterial
      load, and the number of skin lesions were evaluated. Considering the R&J
      classification system as gold standard, ML Flow tests correctly allocated 70%
      patients in the PB group and 87% in the MB group. The classification based on
      counting the number of skin lesions correctly allocated 46% PB patients and 99%
      MB leprosy cases. Slit skin smears properly classified 91% and 97% of PB and MB
      patients, respectively. Based on U-MDT/CT-BR results, classification of leprosy
      patients for treatment purposes is unnecessary because it does not impact
      clinical and laboratories outcomes. In this context, the identification of new
      biomarkers to detect patients at a higher risk to develop leprosy reactions or
      relapse remains an important research challenge. 

PMID- 25940193
TI  - Evaluation of nucleic acid stabilization products for ambient temperature
      shipping and storage of viral RNA and antibody in a dried whole blood format.
AB  - Loss of sample integrity during specimen transport can lead to false-negative
      diagnostic results. In an effort to improve upon the status quo, we used dengue
      as a model RNA virus to evaluate the stabilization of RNA and antibodies in three
      commercially available sample stabilization products: Whatman FTA Micro Cards (GE
      Healthcare Life Sciences, Pittsburgh, PA), DNAstable Blood tubes (Biomatrica, San
      Diego, CA), and ViveST tubes (ViveBio, Alpharetta, GA). Both contrived and
      clinical dengue-positive specimens were stored on these products at ambient
      temperature or 37 degrees C for up to 1 month. Antibody and viral RNA levels were
      measured by enzyme-linked immunosorbent assay (ELISA) and quantitative reverse
      transcription polymerase chain reaction (qRT-PCR) assays, respectively, and
      compared with frozen unloaded controls. We observed reduced RNA and antibody
      levels between stabilized contrived samples and frozen controls at our earliest
      time point, and this was particularly pronounced for the FTA cards. However,
      despite some time and temperature dependent loss, a 94.6-97.3% agreement was
      observed between stabilized clinical specimens and their frozen controls for all
      products. Additional considerations such as cost, sample volume, matrix, and ease
      of use should inform any decision to incorporate sample stabilization products
      into a diagnostic testing workflow. We conclude that DNAstable Blood and ViveST
      tubes are useful alternatives to traditional filter paper for ambient temperature
      shipment of clinical specimens for downstream molecular and serological testing. 

PMID- 25940194
TI  - Optimizing insecticide allocation strategies based on houses and livestock
      shelters for visceral leishmaniasis control in Bihar, India.
AB  - Visceral leishmaniasis (VL) is the most deadly form of the leishmaniasis family
      of diseases, which affects numerous developing countries. The Indian state of
      Bihar has the highest prevalence and mortality rate of VL in the world.
      Insecticide spraying is believed to be an effective vector control program for
      controlling the spread of VL in Bihar; however, it is expensive and less
      effective if not implemented systematically. This study develops and analyzes a
      novel optimization model for VL control in Bihar that identifies an optimal (best
      possible) allocation of chosen insecticide (dichlorodiphenyltrichloroethane [DDT]
      or deltamethrin) based on the sizes of human and cattle populations in the
      region. The model maximizes the insecticide-induced sandfly death rate in human
      and cattle dwellings while staying within the current state budget for VL vector
      control efforts. The model results suggest that deltamethrin might not be a good
      replacement for DDT because the insecticide-induced sandfly deaths are 3.72 times
      more in case of DDT even after 90 days post spray. Different insecticide
      allocation strategies between the two types of sites (houses and cattle sheds)
      are suggested based on the state VL-control budget and have a direct implication
      on VL elimination efforts in a resource-limited region. 

PMID- 25940195
TI  - Relevance of undetectably rare resistant malaria parasites in treatment failure:
      experimental evidence from Plasmodium chabaudi.
AB  - Resistant malaria parasites are frequently found in mixed infections with drug
      sensitive parasites. Particularly early in the evolutionary process, the
      frequency of these resistant mutants can be extremely low and below the level of
      molecular detection. We tested whether the rarity of resistance in infections
      impacted the health outcomes of treatment failure and the potential for onward
      transmission of resistance. Mixed infections of different ratios of resistant and
      susceptible Plasmodium chabaudi parasites were inoculated in laboratory mice and
      dynamics tracked during the course of infection using highly sensitive genotype
      specific quantitative polymerase chain reaction (qPCR). Frequencies of resistant
      parasites ranged from 10% to 0.003% at the onset of treatment. We found that the
      rarer the resistant parasites were, the lower the likelihood of their onward
      transmission, but the worse the treatment failure was in terms of parasite
      numbers and disease severity. Strikingly, drug resistant parasites had the
      biggest impact on health outcomes when they were too rare to be detected by any
      molecular methods currently available for field samples. Indeed, in the field,
      these treatment failures would not even have been attributed to resistance. 

PMID- 25940196
TI  - High mortality associated with retreatment of tuberculosis in a clinic in
      Kampala, Uganda: a retrospective study.
AB  - The World Health Organization recommends for tuberculosis retreatment a regimen
      of isoniazid (H), rifampicin (R), ethambutol (E), pyrazinamide (Z), and
      streptomycin (S) for 2 months, followed by H, R, E, and Z for 1 month and H, R,
      and E for 5 months. Using data from the National Tuberculosis and Leprosy Program
      registry, this study determined the long-term outcome under programmatic
      conditions of patients who were prescribed the retreatment regimen in Kampala,
      Uganda, between 1997 and 2003. Patients were traced to determine their vital
      status; 62% (234/377) patients were found dead. Having <= 2 treatment courses and
      not completing retreatment were associated with mortality in adjusted analyses. 

PMID- 25940197
TI  - Impact of benznidazole on infection course in mice experimentally infected with
      Trypanosoma cruzi I, II, and IV.
AB  - American trypanosomiasis is an emerging zoonosis in the Brazilian Amazon. Studies
      on benznidazole (BZ) chemotherapy with Trypanosoma cruzi from this region have
      great relevance, given the different discrete typing units (DTUs) that infect
      humans in the Amazon and other regions of Brazil. We performed a parasitological,
      histopathological, and molecular analysis of mice inoculated with strains of T.
      cruzi I, II, and IV that were BZ-treated during the acute phase of infection.
      Groups of Swiss mice were inoculated; 13 received oral BZ, whereas the other 13
      comprised the untreated controls. Unlike parasitemia, the infectivity and
      mortality did not vary among the DTUs. Trypanosoma cruzi DNA was detected in all
      tissues analyzed and the proportion of organs parasitized varied with the
      parasite DTU. The BZ treatment reduced the most parasitological parameters,
      tissue parasitism and the inflammatory processes at all infection stages and for
      all DTUs. However, the number of significant reductions varied according to the
      DTU and infection phase. 

PMID- 25940198
TI  - High seroprevalence of chikungunya virus antibodies among pregnant women living
      in an urban area in Benin, West Africa.
AB  - The aim of this study was to investigate the seroprevalence of antichikungunya
      virus (anti-CHIKV) antibodies in pregnant women living in an urban area of Benin
      (West Africa). Results were obtained by screening sera collected in 2006 and 2007
      with enzyme-linked immunosorbent assay (ELISA) for anti-CHIKV immunoglobulin G
      (IgG) and IgM. Positive results were confirmed by indirect immunofluorescence
      test and microneutralization assay. We found that a large proportion (36.1%) of
      pregnant women living in Cotonou had specific IgG against CHIKV, indicating a
      high seroprevalence of the infection in urban southern Benin, whereas no active
      cases of CHIKV infection were detected. 

PMID- 25940199
TI  - Clinical performance of multiplex high-risk e6 mrna expression in comparison with
      hpv dna subtypes for the identification of women at risk of cervical cancer.
AB  - We compared multiplex E6 messenger ribonucleic acid (mRNA) tests using real-time
      quantitative reverse transcriptase polymerase chain reactions (PCR) with human
      papillomavirus (HPV) DNA subtypes using a MY11/GP6+ PCR-based reverse-blot assay
      to identify cervical intraepithelial neoplasias of grade 2 or worse (CIN2+). In
      total, 684 women were studied, of whom 377 (55%) were diagnosed with CIN2+
      histologically. The specificity of HPV mRNA to predict histological CIN2+ was
      higher than that of HPV DNA (81.3% vs. 44.2%). The odds ratios (ORs) to predict
      histological CIN2+ in women with positive for type 16, 18, 31, and 45 E6 mRNA or
      by HPV DNA detection were 7.1 (95% confidence interval [CI] 3.9-13.1) and 2.5
      (95%CI 1.9-3.5), respectively, compared to those with negative for E6 mRNA or HPV
      DNA. The OR to predict histological CIN2+ in women with a cytological grade
      <CIN2+ and positive for type 16, 18, 31, and 45 E6 mRNA was 9.7 (95%CI 3.2-29.2),
      compared to those with a cytological grade <CIN2+, and negative for E6 mRNA (OR =
      1), those with a cytological grade CIN2+, and negative for mRNA (OR = 6.9, 95%CI
      4.4-10.8), and those with a cytological grade CIN2+ and positive for mRNA (OR =
      28.0, 95%CI 9.8-79.6). As a HPV DNA positive triage, the OR to predict
      histological CIN2+ in women with a cytological grade <CIN2+ and positive for mRNA
      was higher than those with negative for mRNA (OR:12.8 [95%CI 3.6-5.4] vs. OR:1.6
      [95%CI 0.9-2.9]). In conclusion, multiplex HPV E6 mRNA detection can be used as a
      triage for women with cytological grade <CIN2+.

PMID- 25940200
TI  - Recovery of Hearing in Meniere's Disease after Antiviral Treatment.
AB  - OBJECTIVE: Determine the outcome of hearing in Meniere's Disease (MD) after
      antiviral treatment. STUDY DESIGN: Prospective study. SETTING: University
      Hospital. METHODS: Thirty one new patients with a diagnosis of MD were treated
      with antiviral drugs during 2012. Acyclovir or valacyclovir was used depending on
      insurance coverage and cost. A standard dose of 800 mg (acyclovir) or 1g
      (valacyclovir) 3 times a day for 3 weeks was used. The dose was decreased to
      twice daily for three weeks, and finally once daily for a year or longer. Hearing
      test including pure tone average (PTA) and speech discrimination (SD) was
      performed prior to treatment and 1-2 months, 6 months and 1 year after the
      initiation of treatment. Effect on dizziness was recorded at each evaluation,
      hearing was judged to be improved if PTA was lowered by at least 15 db and/or an
      increase in SD of 20% or greater. RESULTS: Hearing was improved in twelve and not
      improved in nineteen patients. Complete control of vertigo was achieved in those
      patients with improved hearing. The nineteen patients with no improvement in
      hearing were divided into 2 groups based on the level of hearing at diagnosis.
      Nine patients presenting with a PTA of 50 db and SD of 50% or better experienced
      good control of vertigo (6 out of 7; 2 with no follow-up). Ten patients with PTA
      of 60 db or more and SD below 50% exhibited poor control of vertigo with
      antivirals (3 out of 10). The duration of MD in the group with hearing
      improvement was shorter (2.4 years) than the group with no improvement (5.5
      years). CONCLUSION: Significant hearing and balance control in patients with MD
      can be achieved with orally administered antiviral drugs.

PMID- 25940201
TI  - Pneumocystis jiroveci pneumonia with recurrent pneumothorax requiring pleurodesis
      in inflammatory bowel disease.

PMID- 25940202
TI  - Clinical utility of bronchoalveolar lavage and respiratory tract biopsies in
      diagnosis and management of suspected invasive respiratory fungal infections in
      children.
AB  - BACKGROUND: Bronchoscopy with bronchoalveolar lavage (BAL) and respiratory tract
      biopsies are important tools for diagnosing fungal infections in children with
      cancer and hematopoietic stem cell transplant (HSCT) recipients. Our objective
      was to evaluate the impact of BAL and respiratory tract biopsies on the
      management of suspected fungal infections in oncology and HSCT patients.
      PROCEDURE: We retrospectively reviewed the medical records of oncology and HSCT
      patients with possible, probable, or proven fungal infection of the respiratory
      tract and determined whether BAL or biopsy following computed tomography (CT)
      prompted a change in management. RESULTS: Among 101 patients (0.5-29 years of
      age), 24 underwent a BAL and 31 had biopsies (27 lung and 4 sinus). The remaining
      46 patients had CT scans only. Of these, there were radiographic findings
      suggestive of a fungal infection in 38 patients (83%). Thirty of these 38
      patients (79%) had a change in management. BAL provided a diagnosis in 6 of 24
      patients (25%). There was a change in management in 2 of the 6 (33%). Respiratory
      tract biopsy provided a diagnosis in 12 of 31 patients (39%). Biopsy results led
      to a change in management in 4 of the 12 patients (33%). Significant
      postoperative morbidity attributed to biopsy occurred in 3 of 31 patients (10%);
      2 patients had pneumothorax requiring chest tube and intubation and a patient had
      prolonged intubation. CONCLUSION: BAL and biopsy in children with an oncological
      diagnosis or those undergoing HSCT only infrequently lead to changes in
      management in the era of empiric therapy with broad-spectrum anti-fungal agents.

PMID- 25940203
TI  - Influence of water availability on gender determination of gametophytes in a
      diploid-polyploid complex of a xerophytic fern genus.
AB  - Environmental sex determination (ESD) is present in several animal and plant
      lineages. Diverse factors such as temperature, light or water availability have
      been described as sex determinants in these organisms. Among plants, ferns
      frequently display ESD. This work compares the effect of different levels of
      water availability in two diploid species of the xerophytic fern genus
      Cheilanthes and in their derived tetraploid, and if they are sensitive to
      antheridiogen (i.e. maleness-inducing pheromone). Different watering regimes were
      applied to isolated gametophyte cultures of the three study species. Gametophyte
      survival, size, gender and sporophyte production were assessed after 13, 18 and
      23 weeks of culture. Cultures combining spores and adult gametophytes were
      established to test the effect of antheridiogen. Isolated gametophytes had an
      asexual to female to bisexual sequence that did not depend upon the degree of
      soil moisture. Both gender expression and growth reduction in response to water
      scarcity of the allotetraploid were more similar to those of one of the diploid
      parents. In all watering regimes, survival was higher in the allotetraploid,
      suggesting hybrid vigour, whereas automixis rate was similar in the three species
      and reached ~50 % at high moisture. This breeding system can ensure reproduction
      in the absence of males. In the three species, female gametophytes produced
      antheridiogens that enhanced maleness. This promotes a mixed mating system that
      could be favourable for ferns growing in xeric habitats. 

PMID- 25940205
TI  - alpha-Terthienylmethanol, isolated from Eclipta prostrata, induces apoptosis by
      generating reactive oxygen species via NADPH oxidase in human endometrial cancer
      cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Eclipta prostrate L. (syn. E. alba Hassk),
      commonly known as False Daisy, has been used in traditional medicine in Asia to
      treat a variety of diseases, including cancer. Although an anti-tumor effect has
      been suggested for E. prostrata, the exact anti-tumor effects and underlying
      molecular mechanisms of its bioactive compounds are poorly understood. The aim of
      this study was to identify compounds with anti-cancer activity from E. prostrata
      and to investigate their mechanism of action. MATERIALS AND METHODS: To assess
      cell viability, cell cycle progression, and apoptosis, we performed MTT assays
      and FACS analysis using Annexin and PI staining. We also investigated reactive
      oxygen species (ROS) production and caspase activation using flow cytometry and
      Western blot analysis, respectively. Cytosolic translocation of cytochrome c was
      measured using an ELISA kit. Antioxidants, MAPK signaling inhibitors, NADPH
      oxidase inhibitors, and siRNA were used to elucidate the molecular mechanism of
      action of the compound. RESULTS: We isolated five terthiophenes from the n-hexane
      fraction of E. prostrata; of these, alpha-terthienylmethanol possessed potent
      cytotoxic activity against human endometrial cancer cells (Hec1A and Ishikawa)
      (IC50<1MUM). The growth inhibitory effect of alpha-terthienylmethanol was
      mediated by the induction of apoptosis, as shown by the accumulation of sub-G1
      and apoptotic cells. In addition, alpha-terthienylmethanol triggered caspase
      activation and cytochrome c release into the cytosol in a time-dependent manner.
      Moreover, alpha-terthienylmethanol increased the intracellular level of ROS and
      decreased that of GSH, and the antioxidants N-acetyl-l-cysteine and catalase
      significantly attenuated alpha-terthienylmethanol-induced apoptosis. We further
      demonstrated that inhibition of the NADPH oxidase attenuated alpha
      terthienylmethanol-induced cell death and ROS accumulation in endometrial cancer
      cells. CONCLUSION: Overall, these results suggest that alpha-terthienylmethanol,
      a naturally occurring terthiophene isolated from E. prostrata, induces apoptosis
      in human endometrial cancer cells by ROS production, partially via NADPH oxidase.

PMID- 25940204
TI  - Plastid phylogenomics of the cool-season grass subfamily: clarification of
      relationships among early-diverging tribes.
AB  - Whole plastid genomes are being sequenced rapidly from across the green plant
      tree of life, and phylogenetic analyses of these are increasing resolution and
      support for relationships that have varied among or been unresolved in earlier
      single- and multi-gene studies. Pooideae, the cool-season grass lineage, is the
      largest of the 12 grass subfamilies and includes important temperate cereals,
      turf grasses and forage species. Although numerous studies of the phylogeny of
      the subfamily have been undertaken, relationships among some 'early-diverging'
      tribes conflict among studies, and some relationships among subtribes of Poeae
      have not yet been resolved. To address these issues, we newly sequenced 25 whole
      plastomes, which showed rearrangements typical of Poaceae. These plastomes
      represent 9 tribes and 11 subtribes of Pooideae, and were analysed with 20
      existing plastomes for the subfamily. Maximum likelihood (ML), maximum parsimony
      (MP) and Bayesian inference (BI) robustly resolve most deep relationships in the
      subfamily. Complete plastome data provide increased nodal support compared with
      protein-coding data alone at nodes that are not maximally supported. Following
      the divergence of Brachyelytrum, Phaenospermateae, Brylkinieae-Meliceae and
      Ampelodesmeae-Stipeae are the successive sister groups of the rest of the
      subfamily. Ampelodesmeae are nested within Stipeae in the plastome trees,
      consistent with its hybrid origin between a phaenospermatoid and a stipoid grass
      (the maternal parent). The core Pooideae are strongly supported and include
      Brachypodieae, a Bromeae-Triticeae clade and Poeae. Within Poeae, a novel sister
      group relationship between Phalaridinae and Torreyochloinae is found, and the
      relative branching order of this clade and Aveninae, with respect to an
      Agrostidinae-Brizinae clade, are discordant between MP and ML/BI trees. Maximum
      likelihood and Bayesian analyses strongly support Airinae and Holcinae as the
      successive sister groups of a Dactylidinae-Loliinae clade. 

PMID- 25940206
TI  - Risk of venous thrombosis after arthroscopy of the knee: results from a large
      population-based case-control study.
AB  - BACKGROUND: From the currently available evidence, the risk of venous thrombosis
      after knee arthroscopy remains unclear. OBJECTIVES: To estimate the risk of
      venous thrombosis after arthroscopy of the knee, and to identify high-risk
      groups. PATIENTS AND METHODS: We used data from a large population-based case
      control study (the Multiple Environmental and Genetic Assessment of risk factors
      for venous thrombosis [MEGA] study) on the etiology of venous thrombosis (4416
      cases; 6150 controls). Odds ratios (ORs) with 95% confidence intervals (CIs),
      adjusted for age, sex, body mass index, rheumatic disease, and regular exercise,
      were calculated. RESULTS: One hundred and three patients and 24 controls had a
      knee arthroscopy in the year before the index date, resulting in a six-fold
      increased risk (OR 5.9, 95% CI 3.7-9.3). Ligament reconstructions led to a higher
      risk (OR 17.2, 95% CI 2.2-136) than meniscal surgery, diagnostic arthroscopy, or
      chondroplasty (OR 5.4, 95% CI 3.4-8.7). An additionally increased risk was found
      for combinations with genetic and acquired risk factors: with oral contraceptives
      (OR 46.6, 95% CI 6.1-353); and with factor V Leiden, factor II G20210A mutation,
      or non-O blood type (OR 15.3, 95% CI 8.1-28.5). The risk of venous thrombosis was
      particularly high in the first 3 months after knee arthroscopy, with an 18-fold
      increased risk (OR 16.2, 95% CI 7.8-33.7). CONCLUSIONS: We observed a strongly
      increased risk of venous thrombosis after knee arthroscopy, especially in the
      first months after the procedure. The risk was particularly high in the presence
      of other acquired or genetic risk factors, making knee arthroscopy a high-risk
      intervention in certain individuals.

PMID- 25940207
TI  - The invasive coral Oculina patagonica has not been recently introduced to the
      Mediterranean from the western Atlantic.
AB  - BACKGROUND: Effective policies, management, and scientific research programs
      depend on the correct identification of invasive species as being either native
      or introduced. However, many species continue to be misidentified. Oculina
      patagonica, first recorded in the Mediterranean Sea in 1966, is believed to have
      been introduced in anthropogenic times and expanding in a west to east direction.
      However, its present identification and status as a recently introduced species
      remain to be explored. In this study, we used multi-locus genetic data to test
      whether O. patagonica in the Mediterranean has been recently introduced from the
      western North Atlantic. RESULTS: We found no genetic or historical demographic
      evidence to support a recent introduction of O. patagonica from the western North
      Atlantic or an expansion across the Mediterranean. Instead, Mediterranean and
      Atlantic populations are genetically distinct and appear to have begun diverging
      about 5 Mya. We also found evidence of a fossil record of Oculina spp. existing
      in the eastern North Atlantic millions of years before the present. CONCLUSIONS:
      Our results suggest that Mediterranean populations of O. patagonica have long
      been isolated from the western Atlantic, either in undetectable numbers or
      overlooked and undersampled sites and habitats, and have only recently been
      expanding to invasive levels as a result of environmental changes. Accurate
      identification of species' invasive statuses will enable more effective research
      programs aimed at better understanding the mechanisms promoting the invasive
      nature of species, which can then lead to the implementation of efficient
      management plans.

PMID- 25940208
TI  - Modified Single Versus Double-Patch Technique for the Repair of Complete
      Atrioventricular Septal Defect.
AB  - OBJECTIVES: We present our single center results of two commonly used surgical
      techniques, the modified single-patch and double-patch technique for the repair
      of the complete atrioventricular septal defect. METHODS: We enrolled 49 patients
      with complete atrioventricular septal defect who were operated by a single
      surgeon between 2004 and 2014. The modified single-patch technique was performed
      in 32 cases (group S), whereas the defect was repaired with the double-patch
      technique in 17 patients (group D). RESULTS: The mean age at the time of
      operation was 7.7 +/- 8.6 (range 1-48) months and 9.9 +/- 12.5 (range 1.5-48)
      months, in groups S and D, respectively. Mean body weight was 6.7 +/- 3 (range
      3.5-15.5) kilograms and 7.2 +/- 3.8 (range 4.3-14.5) kilograms in groups S and D,
      respectively. Cross-clamp and cardiopulmonary bypass times were shorter in the
      modified single-patch group (65.6 +/- 16.3 vs. 98.7 +/- 19.8 minutes, p = 0.0001;
      88.9 +/- 23.3 vs. 128.9 +/- 28.0 minutes, p = 0.0001). Postoperative
      atrioventricular valve function was improved in both groups. Mean follow-up
      period was 4.4 +/- 3.2 (range 1.2-9.9) years. One patient in each group underwent
      reoperation for left atrioventricular valve insufficiency. We encountered two
      early and one late mortalities in modified single-patch group. One early
      mortality was experienced in the unmodified group. CONCLUSIONS: The modified
      single-patch and two-patch techniques have comparable results; however, the
      modified single-patch technique is performed with significantly shorter cross
      clamp and cardiopulmonary bypass times, therefore we have adopted this technique
      on a routine basis for the treatment of the complete atrioventricular septal
      defect in our institute.

PMID- 25940209
TI  - Synchronous Pleomorphic Adenoma and Invasive Ductal Carcinoma in Distinct
      Breasts.

PMID- 25940210
TI  - Neurosurgery Residency Websites: A Critical Evaluation.
AB  - OBJECTIVE: To evaluate the accessibility of educational and recruitment content
      of Neurosurgery Residency Websites (NRWs). METHODS: Program lists from the
      Fellowship and Residency Electronic Interactive Database (FREIDA), Electronic
      Residency Application Service (ERAS), and the American Association of
      Neurological Surgeons (AANS) were accessed for the 2015 Match. These databases
      were assessed for accessibility of information and responsive program contacts.
      Presence of online recruitment and education variables was assessed, and
      correlations between program characteristics and website comprehensiveness were
      made. RESULTS: All 103 neurosurgery residency programs had an NRW. The AANS
      database provided the most number of viable website links with 65 (63%). No links
      existed for 5 (5%) programs. A minority of programs contacts responded via e-mail
      (46%). A minority of recruitment (46%) and educational (49%) variables were
      available on the NRWs. Larger programs, as defined by the number of yearly
      residency spots and clinical faculty, maintained greater online content than
      smaller programs. Similar trends were seen with programs affiliated with a ranked
      medical school and hospital. CONCLUSIONS: Multiple prior studies have
      demonstrated that medical students applying to neurosurgery rely heavily on
      residency program websites. As such, the paucity of content on NRWs allows for
      future opportunity to optimize online resources for neurosurgery training. Making
      sure that individual programs provide relevant content, make the content easier
      to find and adhere to established web design principles could increase the
      usability of NRWs.

PMID- 25940211
TI  - A Single-Center Experience with the NeuroPace RNS System: A Review of Techniques
      and Potential Problems.
AB  - INTRODUCTION: The clinical results for the RNS System (NeuroPace, Mountain View,
      California, USA) closed-loop responsive neurostimulator for the treatment of
      medically intractable partial-onset seizures have been encouraging. The
      University of Southern California (USC) Neurorestoration Center and the Keck
      Hospital of USC have become the world's first institutions to implant an RNS
      System post U.S. Food and Drug Administration (FDA) approval. As one of the study
      centers, we review our experience with our group of patients who have been
      implanted with the RNS System. METHODS: A total of 40 surgeries by a single
      surgeon were performed on 10 patients (7 male and 3 female) with an average age
      of 39.2 years (24-66 years) and were followed for an average of 45 months (30-54
      months). The average age at seizure onset was 14 years (birth-37 years) with an
      average of 4.7 (3-12) failed antiepileptic drugs. We reviewed the patients'
      charts for complications from the surgeries including infections requiring
      surgical intervention, hematomas, hardware failures, and death. RESULTS: Of the
      40 surgeries, there were 10 initial implantations of the neurostimulator and
      leads, 24 neurostimulator replacements for expected end of neurostimulator
      service, 2 incision and drainage procedures (I & Ds) for soft tissue infection
      followed by 1 explantation and 1 reimplantation (same patient), and 2 revisions
      because of one lead that was damaged at the exit point between the skull and a
      titanium mesh and the second lead that was damaged at an acute bend over the
      skull (same patient). Eight of the patients had no complications and underwent an
      average of 2.7 neurostimulator replacements over 7 consecutive years to date.
      Each patient underwent routine postoperative computed tomography imaging of the
      brain, and none had any intracranial hematomas or misplaced leads requiring
      revision surgery. Finally, there were no deaths in our patient population.
      CONCLUSIONS: Our experience with the NeuroPace RNS System over an average follow
      up of 45 months suggests that the surgery and device are safe when placed by an
      experienced surgeon. Although there were no clinically significant hematomas or
      patient deaths, we did have 1 patient each with infection and lead damage at the
      point of exit from the skull. We compare the results of this study with other
      neuromodulation procedures for epilepsy to evaluate the safety and complications
      associated with the RNS System. Our initial experience suggests that the RNS
      System can be readily incorporated into an active epilepsy surgical center.

PMID- 25940212
TI  - Nucleus accumbens stimulation in partial epilepsy--a randomized controlled case
      series.
AB  - Neuromodulative treatment options are warranted in patients with difficult-to
      treat epilepsy. However, acquisition of controlled data on deep brain stimulation
      has so far been achieved only for the centromedian and anterior thalamic nucleus.
      In a case series of four patients with intractable partial epilepsy, a randomized
      controlled cross-over protocol was used to get insight into efficacy and safety
      of 3-month nucleus accumbens stimulation. Seizure frequency, neurocognitive
      testing, "Liverpool Seizure Severity Score," "Quality of Life in Epilepsy
      Inventory," "Beck Depression Inventory," and "Mini International Neuropsychiatric
      Interview" were obtained at every visit. In a subsequent open-label phase,
      nucleus accumbens stimulation responders underwent concomitant anterior thalamic
      nucleus stimulation, whereas nonresponders received solely thalamic stimulation.
      Under nucleus accumbens stimulation, three of four patients had >= 50% reduction
      in frequency of disabling seizures without further improvement with additional
      anterior thalamic nucleus stimulation. Patient-reported outcome and
      neurocognitive testing remained unchanged. Accumbens stimulation is safe and
      seems to be a suitable option in intractable partial epilepsy. The current
      findings require substantiation by an adequately powered multicenter study.

PMID- 25940213
TI  - Use of the aquatic plant Elodea canadensis to assess toxicity and genotoxicity of
      Yenisei River sediments.
AB  - The toxicity, cytotoxicity, and genotoxicity of bulk sediments from the Yenisei
      River (Siberia, Russia) were estimated in laboratory bioassays based on several
      endpoints in the aquatic plant Elodea canadensis. The bottom sediment samples
      were collected in the Yenisei River upstream and downstream of the sources of
      chemical and radioactive contamination. The testing revealed different
      sensitivities of Elodea endpoints to the quality of the bottom sediment: weight
      of shoots < length of shoots < mitotic index < length of roots < percentage of
      abnormal cells. The response of the genotoxicity endpoint (percentage of cells
      with chromosome abnormalities in roots of Elodea) was the highest in sediments
      with chemical pollution, whereas the highest inhibition of toxicity endpoints
      (shoot and root length) occurred in sediments with the highest level of
      radioactive pollution. The extreme response of Elodea endpoints to the quality of
      certain sediment samples may be regarded as related to the possible presence of
      unknown toxicants. The results show that E. canadensis can be used as an
      indicator species in laboratory contact testing of bottom sediment. The responses
      of shoot and root length growth endpoints of Elodea can be recommended as basic
      sensitivity indicators of bottom sediment toxicity. Analysis of cells carrying
      abnormal chromosomes in the apical root meristem of Elodea can be performed
      optionally in the same test to assess the genotoxicity of sediments.

PMID- 25940214
TI  - Ecthyma Gangrenosum Caused by Escherichia coli in a Previously Healthy Girl.
AB  - Ecthyma gangrenosum is a characteristic lesion of Pseudomonas aeruginosa sepsis
      in immunocompromised patients. Only eight cases of ecthyma gangrenosum caused by
      Escherichia coli have been reported. We report a case of ecthyma gangrenosum due
      to E. coli without bacteremia in a previously healthy girl. 

PMID- 25940216
TI  - Synthesis of nisin AB dicarba analogs using ring-closing metathesis: influence of
      sp(3) versus sp(2) hybridization of the alpha-carbon atom of residues
      dehydrobutyrine-2 and dehydroalanine-5 on the lipid II binding affinity.
AB  - Herein the synthesis of two nisin AB dicarba analogs is described, focusing on
      amino acid modifications at positions 2 and 5. The nisin mimics were synthesized
      by a combination of solid phase synthesis of the linear peptides, followed by
      macrocyclization via ring-closing metathesis and fragment assembly by means of
      solution phase chemistry. The two N-terminal nisin AB-fragment mimics contain
      either the native dehydrobutyrine (Dhb)/dehydroalanine (Dha) amino acid residues
      or alanine at position 2 and 5, respectively. The native dehydrobutyrine at
      position 2 and dehydroalanine at position 5 were introduced as their precursors,
      namely threonine and serine, respectively, and subsequent dehydration was carried
      out by EDCI/CuCl as the condensing agent. Both AB-fragment mimics were analyzed
      in a lipid II binding assay and it was found that the Ala2/Ala5 AB-mimic (2)
      showed a reduced activity, while the Dhb2/Dha5 AB-mimic (3) was as active as the
      native AB-fragment (1).

PMID- 25940215
TI  - Impact of Implantable Cardioverter Defibrillators on Survival of Patients with
      Centrifugal Left Ventricular Assist Devices.
AB  - BACKGROUND: Both implantable cardioverter defibrillators (ICDs) and left
      ventricular assist devices (LVADs) have a positive impact on survival in the
      heart failure population. We sought to determine whether these positive effects
      on survival are additive or whether LVAD therapy supersedes ICD therapy. METHOD:
      We analyzed survival data of patients implanted with nonpulsatile LVADs between
      October 2004 and March 2013. Survival in patients with ICDs (n = 64) was compared
      to those without ICDs (n = 36). Patients exited the study at the time of heart
      transplantation or death. RESULTS: A total of 100 patients underwent LVAD
      implantation during this time. Patients had a mean follow-up time of 364 +/- 295
      days. Death occurred in 15 (38%) patients in the no ICD group versus 18 (30%) in
      the ICD group. Univariate analysis demonstrated a marginal early survival benefit
      at up to 1 year post-LVAD implant in the ICD cohort; however, at time points
      greater than 1 year there was no statistically significant benefit in ICD therapy
      in LVAD patients (P = 0.56). Multivariate analysis did not show any significant
      predictor of survival. There were no patients who died of sudden cardiac death.
      There was no significant difference in the time to heart transplantation (443
      days +/- 251 no ICD vs 372 days +/- 277 ICD, P = 0.37). CONCLUSION: The benefit
      of ICD therapy in the setting of continuous flow LVAD therapy is uncertain.
      Although prolonged ventricular arrhythmias (VAs) may potentially impact on
      patient survival, LVAD therapy is beneficial in prevention of sudden cardiac
      death due to VAs.

PMID- 25940218
TI  - Similar patterns of frequency-dependent selection on animal personalities emerge
      in three species of social spiders.
AB  - Frequency-dependent selection is thought to be a major contributor to the
      maintenance of phenotypic variation. We tested for frequency-dependent selection
      on contrasting behavioural strategies, termed here 'personalities', in three
      species of social spiders, each thought to represent an independent evolutionary
      origin of sociality. The evolution of sociality in the spider genus Anelosimus is
      consistently met with the emergence of two temporally stable discrete personality
      types: an 'aggressive' or 'docile' form. We assessed how the foraging success of
      each phenotype changes as a function of its representation within a colony. We
      did this by creating experimental colonies of various compositions (six
      aggressives, three aggressives and three dociles, one aggressive and five
      dociles, six dociles), maintaining them in a common garden for 3 weeks, and
      tracking the mass gained by individuals of either phenotype. We found that both
      the docile and aggressive phenotypes experienced their greatest mass gain in
      mixed colonies of mostly docile individuals. However, the performance of both
      phenotypes decreased as the frequency of the aggressive phenotype increased.
      Nearly identical patterns of phenotype-specific frequency dependence were
      recovered in all three species. Naturally occurring colonies of these spiders
      exhibit mixtures dominated by the docile phenotype, suggesting that these spiders
      may have evolved mechanisms to maintain the compositions that maximize the
      success of the colony without compromising the expected reproductive output of
      either phenotype.

PMID- 25940219
TI  - Synthesis of copper ion incorporated horseradish peroxidase-based hybrid
      nanoflowers for enhanced catalytic activity and stability.
AB  - In this study, we report the preparation, catalytic activity and stability of a
      hybrid nanoflower (hNF) formed from horseradish peroxidase (HRP) enzyme and
      copper ions (Cu(2+)). We studied the morphology of hNFs as a function of the
      concentrations of copper (Cu(2+)) ions, chloride ions (Cl(-)) and HRP enzyme, the
      pH of the buffer solution (phosphate buffered saline), and the temperature of the
      reaction. The effects of morphology on the catalytic activity and stability of
      hNFs were evaluated by oxidation of guaiacol (2-methoxyphenol) to colored 3,3
      dimethoxy-4,4-diphenoquinone in the presence of hydrogen peroxide (H2O2). The
      enhanced activity of hNFs synthesized (from 0.02 mg mL(-1) HRP in 10 mM PBS (pH
      7.4) at +4  degrees C) was 17 595 U mg(-1), which was ~300% higher than free HRP
      in PBS, where it achieved an activity of 5952 U mg(-1). In terms of stability,
      these hNFs stored in PBS buffer at +4  degrees C and room temperature (RT = 20 
      degrees C) lost 4% and 20%, respectively, of their initial catalytic activities
      within 30 days. Finally, we demonstrated that these hNFs can be utilized as
      sensors for the detection of dopamine. 

PMID- 25940217
TI  - Social Support and Human Immunodeficiency Virus-Status Disclosure to Friends and
      Family: Implications for Human Immunodeficiency Virus-Positive Youth.
AB  - PURPOSE: The fear of negative reactions from friends and family members affects
      many human immunodeficiency virus (HIV)-positive adolescents' decisions regarding
      disclosure of their HIV status. The complex relationships and interplay among
      social support, fear of stigma, and disclosure of HIV status need to be better
      understood among youth living with HIV (YLHIV). METHODS: Social support from
      friends and family members and HIV status disclosure were examined among 402
      youth, aged 12-24 years, living with HIV. RESULTS: In separate analyses, (1) HIV
      positive youth who reported more than one close friend and (2) HIV-positive youth
      who reported that friends and family members continued to socialize with them
      after disclosure of their HIV diagnosis, had higher levels of perceived social
      support overall (both p < .05). Furthermore, perceived social support did not
      differ significantly between those participants for whom no family member knew
      their HIV status and those for whom at least one family member knew their status
      (p = .13). Race/ethnicity, sexual orientation, education level, and current
      living situation were not associated with family's knowledge of the participants'
      HIV infection status (p > .07). CONCLUSION: This investigation adds important
      information concerning YLHIV, whose early disclosure experiences may influence
      their resilience and future coping mechanisms regarding experienced stigma, and
      thus influence the length of time they conceal their HIV status, their decision
      to disclose their status, and potentially their decisions regarding treatment.
      Interventions and support systems to assist YLHIV with disclosure, as well as
      medical care, may improve their overall quality of life.

PMID- 25940220
TI  - A naphthalene diimide dyad for fluorescence switch-on detection of G
      quadruplexes.
AB  - A non-fluorescent naphthalene diimide (NDI) dimer, conjugating red and blue NDI
      dyes, becomes red/NIR emitting upon G-quadruplex binding. The fluorescence
      lifetime which is significantly different for the complexes, the G
      quadruplex/dimer and the weakly emitting ds-DNA/dimer is the key feature for the
      development of new rationally engineered G-quadruplex sensors. 

PMID- 25940221
TI  - Topical delivery of dexamethasone acetate from hydrogel containing nanostructured
      liquid carriers and the drug.
AB  - The potential of hydrogel containing nanostructured lipid carriers (NLC) to
      enhance the skin permeation rate and skin deposition of dexamethasone acetate
      (DEA) was investigated. The particle size of obtained NLCs was around 224.4 nm.
      NLCs had core-shell structure and DEA existed in amorphous state in NLCs. The
      permeation rate of DEA through excised mouse skins from hydrogel containing DEA
      NLC (DEA-NLC-hydrogel) was 7.3 times higher than DEA-ointment. The skin
      deposition of DEA from DEA-NLC-hydrogel increased 3.8 folds compared to that from
      solution of DEA in hydrogel (DEA-hydrogel). 

PMID- 25940222
TI  - Isavuconazole: A New Option for the Management of Invasive Fungal Infections.
AB  - OBJECTIVE: To review the pharmacology, chemistry, in vitro susceptibility,
      pharmacokinetics, clinical efficacy, safety, tolerability, dosage, and
      administration of isavuconazole, a triazole antifungal agent. DATA SOURCES:
      Studies and reviews were identified through an English language MEDLINE search
      (1978 to March 2015) and from http://www.clinicaltrials.gov, Food and Drug
      Administration (FDA) briefing documents, program abstracts from international
      symposia, and the manufacturer's Web site. STUDY SELECTION AND DATA EXTRACTION:
      All published and unpublished trials, abstracts, in vitro and preclinical
      studies, and FDA briefing documents were reviewed. DATA SYNTHESIS: Isavuconazole
      has activity against a number of clinically important yeasts and molds, including
      Candida spp, Aspergillus spp, Cryptococcus neoformans, and Trichosporon spp and
      variable activity against the Mucorales. Isavuconazole, available for both oral
      and intravenous administration, is characterized by slow elimination allowing
      once-daily dosing, extensive tissue distribution, and high (>99%) protein
      binding. The most commonly reported adverse events, which are mild and limited in
      nature, include nausea, diarrhea, and elevated liver function tests. Its drug
      interaction potential appears to be similar to other azole antifungals but less
      than those observed with voriconazole. Comparative trials are under way or have
      been recently completed for the treatment of candidemia, invasive candidiasis and
      aspergillosis, and rare mold infections. CONCLUSIONS: Isavuconazole has a broad
      spectrum of activity and favorable pharmacokinetic properties, providing an
      advantage over other currently available broad-spectrum azole antifungals and a
      clinically useful alternative to voriconazole for the treatment of invasive
      aspergillosis. It may also prove useful for the treatment of candidemia and
      invasive mold infections; however, these indications await the results of
      clinical trials.

PMID- 25940223
TI  - Molecular design of triazine and carbazole based host materials for blue
      phosphorescent organic emitting diodes.
AB  - We synthesized 3-(3-(4,6-diphenyl-1,3,5-triazin-2-yl)-2-methylphenyl)-9-phenyl-9H
      carbazole (TrzmPCz) as a new bipolar host material for blue phosphorescent
      organic light-emitting devices and investigated the electro-optical properties of
      the blue devices fabricated using the TrzmPCz host. We managed the triplet energy
      of the host by inserting a methyl substituent in the phenyl linkage between
      triazine and carbazole. The methyl substituent distorted the backbone structure
      of TrzmPCz and lead to high triplet energy of 2.79 eV. After optimization of the
      device structure, the TrzmPCz based organic light-emitting diodes achieved the
      maximum quantum efficiency of 16.4%, a current efficiency of 32 cd A(-1), and a
      power efficiency of 21.5 lm W(-1). 

PMID- 25940224
TI  - Mammary tissue microenvironment determines T cell-dependent breast cancer
      associated inflammation.
AB  - Although the importance of the host tissue microenvironment in cancer progression
      and metastasis has been established, the spatiotemporal process establishing a
      cancer metastasis-prone tissue microenvironment remains unknown. In this study,
      we aim to understand the immunological character of a metastasis-prone
      microenvironment in a murine 4T1 breast tumor model, by using the activation of
      nuclear factor-kappab (NF-kappaB) in cancer cells as a sensor of inflammatory
      status and by monitoring its activity by bioluminescence imaging. By using a 4T1
      breast cancer cell line stably expressing an NF-kappaB/Luc2 reporter gene (4T1 NF
      kappaB cells), we observed significantly increased bioluminescence approximately
      7 days after metastasis-prone orthotopic mammary fat-pad inoculation but not
      ectopic s.c. inoculation of 4T1 NF-kappaB cells. Such in vivo NF-kappaB
      activation within the fat-pad 4T1 tumor was diminished in immune-deficient SCID
      or nude mice, or T cell-depleted mice, suggesting the requirement of host T cell
      mediated immune responses. Given the fat-pad 4T1 tumor expressed higher
      inflammatory mediators in a T cell-dependent mechanism compared to the s.c.
      tumor, our results imply the importance of the surrounding tissue
      microenvironment for inflaming tumors by collaborating with T cells to instigate
      metastatic spread of 4T1 breast cancer cells. 

PMID- 25940225
TI  - Enhancing the light-driven production of D-lactate by engineering cyanobacterium
      using a combinational strategy.
AB  - It is increasingly attractive to engineer cyanobacteria for bulk production of
      chemicals from CO2. However, cofactor bias of cyanobacteria is different from
      bacteria that prefer NADH, which hampers cyanobacterial strain engineering. In
      this study, the key enzyme d-lactate dehydrogenase (LdhD) from Lactobacillus
      bulgaricus ATCC11842 was engineered to reverse its favored cofactor from NADH to
      NADPH. Then, the engineered enzyme was introduced into Synechococcus elongatus
      PCC7942 to construct an efficient light-driven system that produces d-lactic acid
      from CO2. Mutation of LdhD drove a fundamental shift in cofactor preference
      towards NADPH, and increased d-lactate productivity by over 3.6-fold. We further
      demonstrated that introduction of a lactic acid transporter and bubbling CO2
      enriched air also enhanced d-lactate productivity. Using this combinational
      strategy, increased d-lactate concentration and productivity were achieved. The
      present strategy may also be used to engineer cyanobacteria for producing other
      useful chemicals. 

PMID- 25940227
TI  - Development of Au Disk Nanoelectrode Down to 3 nm in Radius for Detection of
      Dopamine Release from a Single Cell.
AB  - A Au disk nanoelectrode down to 3 nm in radius was developed by a facile and
      reliable method and successfully applied for monitoring dopamine release from
      single living vesicles. A fine etched Au wire was coated with cathodic
      electrophoretic paint followed by polyimide, which retracted from the tip end
      during curing to expose the Au nanotip. By cyclic voltammetric scanning the above
      tip in 0.5 M KCl, the transformation of a core-shaped apex into a geometrically
      well-defined Au disk nanoelectrode with different dimensions can be controllably
      and reproducibly achieved. Scanning electron microscopy, transmission electron
      microscopy, and steady-state voltammetry were used to determine the size of
      nanoelectrodes. The results showed that the specific etching and insulation
      method not only avoids the use of toxic etching solution and the uncontrollable
      treatment to expose the tip but also makes possible the controllable and
      reproducible fabrication of Au disk nanoelectrode down to 3 nm in radius. The
      nanoelectrodes with well-demonstrated analytical performance were further applied
      for amperometrically monitoring dopamine release from single rat pheochromacytoma
      cells with high spatial resolution. 

PMID- 25940226
TI  - Family history of cancer and risk of pediatric and adolescent Hodgkin lymphoma: A
      Children's Oncology Group study.
AB  - Family history of lymphoid neoplasm (LN) is a strong and consistently observed
      Hodgkin lymphoma (HL) risk factor, although it has been only marginally examined
      in pediatric/adolescent patients. Here, healthy control children identified by
      random digit dialing were matched on sex, race/ethnicity and age to HL cases
      diagnosed at 0-14 years at Children's Oncology Group institutions in 1989-2003.
      Detailed histories were captured by structured telephone interviews with parents
      of 517 cases and 783 controls. Epstein-Barr virus (EBV) RNA detection was
      performed for 355 available case tumors. Two analytic strategies were applied to
      estimate associations between family cancer history and pediatric/adolescent HL.
      In a standard case-control approach, multivariate conditional logistic regression
      was used to calculate odds ratios and 95% confidence intervals (CIs). In a
      reconstructed cohort approach, each relative was included as a separate
      observation, and multivariate proportional hazards regression was used to produce
      hazard ratios (HRs) and 95% CIs. Using the latter, pediatric/adolescent HL was
      associated with a positive family history (HR = 1.20, 95% CI: 1.06-1.36),
      particularly early-onset cancers (HR = 1.30, 95% CI: 1.06-1.59) and those in the
      paternal lineage (HR = 1.38, 95% CI: 1.16-1.65), with a suggested association for
      LN in first-degree relatives (HR = 3.61, 95% CI: 0.87-15.01). There were no
      discernable patterns for EBV+ versus EBV- HL. The clustering of LN within
      pedigrees may signal shared genetic susceptibility or common environmental
      exposures. Heritable genetic risk variants have only recently begun to be
      discovered, however. These results are consistent with other studies and provide
      a compelling rationale for family-based studies to garner information about
      genetic susceptibility to HL.

PMID- 25940228
TI  - The mastocyte: the off switch of UV itch.

PMID- 25940229
TI  - Observation of laser-induced electronic structure in oriented polyatomic
      molecules.
AB  - All attosecond time-resolved measurements have so far relied on the use of
      intense near-infrared laser pulses. In particular, attosecond streaking, laser
      induced electron diffraction and high-harmonic generation all make use of non
      perturbative light-matter interactions. Remarkably, the effect of the strong
      laser field on the studied sample has often been neglected in previous studies.
      Here we use high-harmonic spectroscopy to measure laser-induced modifications of
      the electronic structure of molecules. We study high-harmonic spectra of
      spatially oriented CH3F and CH3Br as generic examples of polar polyatomic
      molecules. We accurately measure intensity ratios of even and odd-harmonic
      orders, and of the emission from aligned and unaligned molecules. We show that
      these robust observables reveal a substantial modification of the molecular
      electronic structure by the external laser field. Our insights offer new
      challenges and opportunities for a range of emerging strong-field attosecond
      spectroscopies. 

PMID- 25940231
TI  - Accurate Determination of Amino Acids in Serum Samples by Liquid Chromatography
      Tandem Mass Spectrometry Using a Stable Isotope Labeling Strategy.
AB  - An accurate and sensitive liquid chromatography-tandem mass spectrometry method
      was developed for the analysis of amino acids (isoleucine, leucine, valine,
      tyrosine, phenylalanine and tryptophan) in serum samples using a stable isotope
      labeling strategy. Amino acid samples and standards were, respectively,
      derivatized by 10-methyl-acridone-2-sulfonyl chloride (d0-MASC) and its
      deuterated counterpart d3-MASC to form isotopic pairs which co-eluted and were
      detected by an MS detector at the same time. Accurate internal standard-based
      quantification was thereby achieved without the use of any internal standard
      analogy. The labeling reaction of MASC with amino acids is fast, simple and
      robust. Besides, derivatization increased the molecular weight of amino acids,
      and therefore they were shifted out of the background noise which was often
      observed in low mass region. The instrument LODs were in the range of 1.0-2.5
      nmol/L. Linearities calculated by comparing theoretical peak area ratios of d0
      /d3-MASC derivatives with the experimental peak area ratios were excellent with
      correlation coefficients of >0.995. The proposed method was successfully applied
      to the analysis of amino acids in serum samples with high sensitivity and
      accuracy. 

PMID- 25940232
TI  - Tonic diaphragmatic activity in critically ill children with and without
      ventilatory support.
AB  - BACKGROUND: Infants have to actively maintain their end expiratory lung volume
      (EELV). In mechanically ventilated infants, the diaphragm stays activated until
      the end of expiration (tonic activity), contributing to EELV maintenance. It is
      unclear whether tonic activity compensates for the lack of laryngeal braking due
      to intubation or if it is normally present. OBJECTIVE: To determine if tonic
      diaphragm activity remains after extubation in infants, and if it can be observed
      in older children. METHODS: Prospective observational study of pediatric patients
      ventilated for >24 hr. Diaphragm electrical activity (EAdi) was recorded using a
      specific nasogastric catheter during four periods: (i) the acute phase, (ii) pre
      extubation, (iii) post-extubation, and (iv) at PICU discharge. Tonic EAdi was
      defined as the EAdi in the last quartile of expiration. RESULTS: Fifty-five
      patients, median age 10 months (Interquartile range: 1-48) were studied. In
      infants (<1 year, n = 28), tonic EAdi was always present, and represented 33% (22
      43) of inspiratory EAdi at PICU discharge. No significant change was observed
      between pre- and post-extubation periods. In older patients (n = 27), tonic
      activity was negligible as a whole, but 10 patients exhibited significant tonic
      EAdi at one time-point during PICU stay. Bronchiolitis was the only independent
      factor associated with tonic EAdi. CONCLUSIONS: In infants, tonic EAdi remains
      involved in ventilatory control after extubation and restoration of laryngeal
      braking. Tonic EAdi may play a pathophysiological role in bronchiolitis and it
      can be reactivated in older patients. The interest of tonic EAdi as a tool to
      titrate mechanical ventilation warrants further evaluation.

PMID- 25940234
TI  - Nursing homes and their contracted doctors: Korean experience.

PMID- 25940233
TI  - Dendritic domains with hexagonal symmetry formed by x-shaped bolapolyphiles in
      lipid membranes.
AB  - A novel class of bolapolyphile (BP) molecules are shown to integrate into
      phospholipid bilayers and self-assemble into unique sixfold symmetric domains of
      snowflake-like dendritic shapes. The BPs comprise three philicities: a
      lipophilic, rigid, pi-pi stacking core; two flexible lipophilic side chains; and
      two hydrophilic, hydrogen-bonding head groups. Confocal microscopy, differential
      scanning calorimetry, XRD, and solid-state NMR spectroscopy confirm BP-rich
      domains with transmembrane-oriented BPs and three to four lipid molecules per BP.
      Both species remain well organized even above the main 1,2-dipalmitoyl-sn-glycero
      3-phosphocholine transition. The BP molecules only dissolve in the fluid membrane
      above 70  degrees C. Structural variations of the BP demonstrate that head-group
      hydrogen bonding is a prerequisite for domain formation. Independent of the head
      group, the BPs reduce membrane corrugation. In conclusion, the BPs form
      nanofilaments by pi stacking of aromatic cores, which reduce membrane corrugation
      and possibly fuse into a hexagonal network in the dendritic domains. 

PMID- 25940235
TI  - Regarding the Study by Fortes et al About the Assessment of Hydration in the
      Elderly.

PMID- 25940230
TI  - Benefits of the Mediterranean Diet: Insights From the PREDIMED Study.
AB  - The PREDIMED (PREvencion con DIeta MEDiterranea) multicenter, randomized, primary
      prevention trial assessed the long-term effects of the Mediterranean diet
      (MeDiet) on clinical events of cardiovascular disease (CVD). We randomized 7447
      men and women at high CVD risk into three diets: MeDiet supplemented with extra
      virgin olive oil (EVOO), MeDiet supplemented with nuts, and control diet (advice
      on a low-fat diet). No energy restriction and no special intervention on physical
      activity were applied. We observed 288 CVD events (a composite of myocardial
      infarction, stroke or CVD death) during a median time of 4.8years; hazard ratios
      were 0.70 (95% CI, 0.53-0.91) for the MeDiet+EVOO and 0.70 (CI, 0.53-0.94) for
      the MeDiet+nuts compared to the control group. Respective hazard ratios for
      incident diabetes (273 cases) among 3541 non-diabetic participants were 0.60
      (0.43-0.85) and 0.82 (0.61-1.10) for MeDiet+EVOO and MeDiet+nuts, respectively
      versus control. Significant improvements in classical and emerging CVD risk
      factors also supported a favorable effect of both MeDiets on blood pressure,
      insulin sensitivity, lipid profiles, lipoprotein particles, inflammation,
      oxidative stress, and carotid atherosclerosis. In nutrigenomic studies beneficial
      effects of the intervention with MedDiets showed interactions with several
      genetic variants (TCF7L2, APOA2, MLXIPL, LPL, FTO, M4CR, COX-2, GCKR and
      SERPINE1) with respect to intermediate and final phenotypes. Thus, the PREDIMED
      trial provided strong evidence that a vegetable-based MeDiet rich in unsaturated
      fat and polyphenols can be a sustainable and ideal model for CVD prevention. 

PMID- 25940237
TI  - Identification of previously unknown SERPINB7 splice variants in patients with
      Nagashima-type palmoplantar keratosis reveals the importance of the CD-loop of
      SERPINB7.

PMID- 25940236
TI  - Development and psychometric properties of the family distress in advanced
      dementia scale.
AB  - OBJECTIVE: The majority of scales to measure family member distress in dementia
      are designed for community settings and do not capture the unique burdens of the
      nursing home (NH) environment. We report the psychometric properties of a new
      Family Distress in Advanced Dementia Scale for use in the NH setting. DESIGN,
      SETTING, PARTICIPANTS: Cross-sectional questionnaire of 130 family member health
      care proxies of NH residents with advanced dementia in 31 Boston-area NHs.
      METHODS: Thirty-one initial items were evaluated, measuring the frequency over
      the past 3 months of sources of distress. Exploratory factor analysis identified
      domains of distress; Cronbach's alpha was computed for each domain. Associations
      between the domains and other measures were evaluated using Pearson correlation
      coefficients, including measures of depression (PHQ-9), satisfaction with care
      (Satisfaction with Care at the End-of-Life in Dementia [SWC-EOLD]), and caregiver
      burden (Zarit Burden Interview short version). RESULTS: Factor analysis suggested
      3 domains: emotional distress (9 items), dementia preparedness (5 items), and NH
      relations (7 items). Cronbach's alpha coefficients were 0.82, 0.75, and 0.83
      respectively. The PHQ-9 correlated most strongly with the emotional distress
      factor (r = 0.34), the SWC-EOWD correlated most strongly with the NH relations
      factor (r = 0.35), as did the Zarit Burden Scale (r = 0.50). CONCLUSIONS: The
      Family Distress in Advanced Dementia Scale encompasses 3 domains of distress.
      This scale represents a much needed tool to assess distress among family members
      of NH residents with advanced dementia and provides a metric to evaluate
      interventions in the population.

PMID- 25940238
TI  - Expression, purification, and characterization of a bifunctional 99-kDa
      peptidoglycan hydrolase from Pediococcus acidilactici ATCC 8042.
AB  - Pediococcus acidilactici ATCC 8042 is a lactic acid bacteria that inhibits
      pathogenic microorganisms such as Staphylococcus aureus through the production of
      two proteins with lytic activity, one of 110 kDa and the other of 99 kDa. The 99
      kDa one has high homology to a putative peptidoglycan hydrolase (PGH) enzyme
      reported in the genome of P. acidilactici 7_4, where two different lytic domains
      have been identified but not characterized. The aim of this work was the
      biochemical characterization of the recombinant enzyme of 99 kDa. The enzyme was
      cloned and expressed successfully and retains its activity against Micrococcus
      lysodeikticus. It has a higher N-acetylglucosaminidase activity, but the N
      acetylmuramoyl-L-alanine amidase can also be detected spectrophotometrically. The
      protein was then purified using gel filtration chromatography. Antibacterial
      activity showed an optimal pH of 6.0 and was stable between 5.0 and 7.0. The
      optimal temperature for activity was 60  degrees C, and all activity was lost
      after 1 h of incubation at 70  degrees C. The number of strains susceptible to
      the recombinant 99-kDa enzyme was lower than that susceptible to the mixture of
      the 110- and 99-kDa PGHs of P. acidilactici, a result that suggests synergy
      between these two enzymes. This is the first PGH from LAB that has been shown to
      possess two lytic sites. The results of this study will aid in the design of new
      antibacterial agents from natural origin that can combat foodborne disease and
      improve hygienic practices in the industrial sector.

PMID- 25940239
TI  - Independent validation of four-dimensional flow MR velocities and vortex ring
      volume using particle imaging velocimetry and planar laser-Induced fluorescence.
AB  - PURPOSE: This study aimed to: (i) present and characterize a phantom setup for
      validation of four-dimensional (4D) flow using particle imaging velocimetry (PIV)
      and planar laser-induced fluorescence (PLIF); (ii) validate 4D flow velocity
      measurements using PIV; and (iii) validate 4D flow vortex ring volume (VV) using
      PLIF. METHODS: A pulsatile pump and a tank with a 25-mm nozzle were constructed.
      PIV measurements (1.5 * 1.5 mm pixels, temporal resolution 10 ms) were obtained
      on two occasions. The 4D flow (3 * 3 * 3 mm voxels, temporal resolution 50 ms)
      was acquired using SENSE = 2. VV was quantified using PLIF and 4D flow. RESULTS:
      PIV showed excellent day-to-day stability (R(2) = 0.99, bias -0.04 +/- 0.72
      cm/s). The 4D flow mean velocities agreed well with PIV (R(2) = 0.95, bias 0.16
      +/- 2.65 cm/s). Peak velocities in 4D flow were underestimated by 7-18% compared
      with PIV (y = 0.79x + 2.7, R(2) = 0.96, -12 +/- 5%). VV showed excellent
      agreement between PLIF and 4D flow (R(2) = 0.99, 2.4 +/- 1.5 mL). CONCLUSION:
      This study shows: (i) The proposed phantom enables reliable validation of 4D
      flow. (ii) 4D flow velocities show good agreement with PIV, but peak velocities
      were underestimated due to low spatial and temporal resolution. (iii) Vortex ring
      volume (VV) can be quantified using 4D flow.

PMID- 25940240
TI  - A structure-directing method to prepare semiconductive zeolitic cluster-organic
      frameworks with Cu3I4 building units.
AB  - Two semiconductive cluster-organic frameworks based on Cu4I4 and Cu3I4 building
      units were obtained by the use of different organic structure-directing agents;
      the latter Cu3I4 nodes are tetrahedrally connected through 1,4
      diazabicyclo[2.2.2]octane (DABCO) linkers and Cu-I bridges, giving rise to a
      zeolitic framework with SOD topology. 

PMID- 25940241
TI  - Reducing COPD readmissions: great promise but big problems.

PMID- 25940242
TI  - The chef has a knife...: endoscopic ultrasound-guided fine-needle aspiration by a
      pulmonologist.

PMID- 25940243
TI  - Lymph nodes in lung cancer: location, location, and location?

PMID- 25940244
TI  - Ease of delivery is not so easy.

PMID- 25940245
TI  - Point: does spontaneous bacterial empyema occur? Yes.

PMID- 25940246
TI  - Counterpoint: does spontaneous bacterial empyema occur? No.

PMID- 25940247
TI  - Rebuttal from Dr Lai et al.

PMID- 25940248
TI  - Rebuttal from Dr Nguyen et al.

PMID- 25940249
TI  - Ambulatory extracorporeal membrane oxygenation as a bridge to lung
      transplantation: walking while waiting.
AB  - The proportion of critically ill patients awaiting lung transplantation has
      increased since the implementation of the Lung Allocation Score (LAS) in 2005.
      Critically ill patients comprise a sizable proportion of wait-list mortality and
      are known to experience increased posttransplant complications. These critically
      ill patients have been successfully bridged to lung transplantation with
      extracorporeal membrane oxygenation (ECMO), but historically these patients have
      required excessive sedation, been immobile, and have had difficult functional
      recovery in the posttransplant period and high mortality. One solution to the
      deconditioning often seen in critically ill patients is the implementation of
      rehabilitation and ambulation while awaiting transplantation on ECMO. Ambulatory
      ECMO programs of this nature have been developed in an attempt to provide
      rehabilitation, physical therapy, and minimization of sedation prior to lung
      transplantation to improve both surgical and posttransplant outcomes. Favorable
      outcomes have been reported using this novel approach, but how and where this
      strategy should be implemented remain unclear. In this commentary, we review the
      currently available literature for ambulation and rehabilitation during ECMO
      support as a bridge to lung transplantation, discuss future directions for this
      technology, and address the important issues of resource allocation and
      regionalization of care as they relate to ambulatory ECMO. 

PMID- 25940251
TI  - Diagnosing and staging lung cancer involving the mediastinum.
AB  - The purpose of this article is to provide an update on evidence-based methods for
      mediastinal staging in patients with lung cancer. This is a review of the
      recently published studies and a summary of relevant guidelines addressing the
      role of CT scan, PET scan, endobronchial ultrasound transbronchial needle
      aspiration (EBUS-TBNA), and mediastinoscopy as pertinent to lung cancer staging
      and restaging. The focus is on how these diagnostic methods fit into the best
      algorithm for patients with chest imaging abnormalities suspected of malignant
      disease. Several studies, meta-analyses, and systematic reviews specifically
      targeted the role of PET scan, EBUS-TBNA, and mediastinoscopy for detecting
      mediastinal lymph node involvement in patients suffering from lung cancer. Based
      on the recommendations from the currently published guidelines, algorithms of
      care are proposed for staging and restaging of the mediastinum. 

PMID- 25940250
TI  - Predischarge bundle for patients with acute exacerbations of COPD to reduce
      readmissions and ED visits: a randomized controlled trial.
AB  - BACKGROUND: Hospital readmissions for acute exacerbations of COPD (AECOPDs) pose
      burdens to the health-care system and patients. A current gap in knowledge is
      whether a predischarge screening and educational tool administered to patients
      with COPD reduces readmissions and ED visits. METHODS: A single-center,
      randomized trial of admitted patients with AECOPDs was conducted at Henry Ford
      Hospital between February 2010 and April 2013. One hundred seventy-two patients
      were randomized to either the control (standard care) or the bundle group in
      which patients received smoking cessation counseling, screening for
      gastroesophageal reflux disease and depression or anxiety, standardized inhaler
      education, and a 48-h postdischarge telephone call. The primary end point was the
      difference in the composite risk of hospitalizations or ED visits for AECOPD
      between the two groups in the 30 days following discharge. A secondary end point
      was 90-day readmission rate. RESULTS: Of the 172 patients, 18 of 79 in the
      control group (22.78%) and 18 of 93 in the bundle group (19.35%) were readmitted
      within 30 days. The risk of ED visits or hospitalizations within 30 days was not
      different between the groups (risk difference, -3.43%; 95% CI, -15.68% to 8.82%;
      P = .58). Overall, the time to readmission in 30 and 90 days was similar between
      groups (log-rank test P = .71 and .88, respectively). CONCLUSIONS: A predischarge
      bundle intervention in AECOPD is not sufficient to reduce the 30-day risk of
      hospitalizations or ED visits. More resources may be needed to generate a
      measurable effect on readmission rates. TRIAL REGISTRY: ClinicalTrials.gov; No.:
      NCT02135744; URL: www.clinicaltrials.gov.

PMID- 25940253
TI  - The effect of OSA on work disability and work-related injuries.
AB  - OSA is a common yet underdiagnosed respiratory disorder characterized by
      recurrent upper airway obstruction during sleep. OSA results in sleep
      fragmentation and repetitive hypoxemia and is associated with a variety of
      adverse consequences including excessive daytime sleepiness, reduced quality of
      life, cardiovascular disease, decreased learning skills, and neurocognitive
      impairment. Neurocognitive impairments that have been linked to poor sleep
      include memory deficits, decreased learning skills, inability to concentrate, and
      decreased alertness. Furthermore, the societal and economic costs of OSA are
      substantial; for example, patients with OSA have a significantly greater risk of
      motor vehicle crashes, consume more health-care resources, and have associated
      annual costs in the billions of dollars per year. It is increasingly recognized
      that OSA may also have substantial economic consequences. Specifically, there is
      accumulating evidence implicating OSA as an important contributor to work
      disability (including absenteeism, presenteeism) and work-related injuries. This
      review summarizes the current state of knowledge in these two areas. 

PMID- 25940254
TI  - Mobile health: assessing the barriers.
AB  - Mobile health (mHealth) combines the decentralization of health care with patient
      centeredness. Mature mHealth applications (apps) and services could provide
      actionable information, coaching, or alerts at a fraction of the cost of
      conventional health care. Different categories of apps attract diverse safety and
      privacy regulation. It is too early to tell whether these apps can overcome
      questions about their use cases, business models, and regulation. 

PMID- 25940252
TI  - Antimicrobial resistance in hospital-acquired gram-negative bacterial infections.
AB  - Aerobic gram-negative bacilli, including the family of Enterobacteriaceae and non
      lactose fermenting bacteria such as Pseudomonas and Acinetobacter species, are
      major causes of hospital-acquired infections. The rate of antibiotic resistance
      among these pathogens has accelerated dramatically in recent years and has
      reached pandemic scale. It is no longer uncommon to encounter gram-negative
      infections that are untreatable using conventional antibiotics in hospitalized
      patients. In this review, we provide a summary of the major classes of gram
      negative bacilli and their key mechanisms of antimicrobial resistance, discuss
      approaches to the treatment of these difficult infections, and outline methods to
      slow the further spread of resistance mechanisms. 

PMID- 25940256
TI  - Correction to table and text in: sputum plasminogen activator inhibitor-1
      elevation by oxidative stress-dependent nuclear factor-kappaB activation in COPD.

PMID- 25940255
TI  - Starting a lung transplant program: a roadmap for long-term excellence.
AB  - Lung transplantation is an effective therapy for many patients with end-stage
      lung disease. Few centers across the United States offer this therapy, as a
      successful lung transplant program requires significant institutional resources
      and specialized personnel. Analysis of the United Network of Organ Sharing
      database reveals that the failure rate of new programs exceeds 40%. These data
      suggest that an accurate assessment of program viability as well as a strategy to
      continuously assess defined quality measures is needed. As part of strategic
      planning, regional availability of recipient and donors should be assessed.
      Additionally, analysis of institutional expertise at the physician, support
      staff, financial, and administrative levels is necessary. In May of 2007, we
      started a new lung transplant program at the University of Iowa Hospitals and
      Clinics and have performed 101 transplants with an average recipient 1-year
      survival of 91%, placing our program among the top in the country for the past 5
      years. Herein, we review internal and external factors that impact the viability
      of a new lung transplant program. We discuss the use of four prospectively
      identified quality measures: volume, recipient outcomes, financial solvency, and
      academic contribution as one approach to achieve programmatic excellence. 

PMID- 25940257
TI  - Error in title of: hybrid rotational angiography-guided localization single-port
      lobectomy.

PMID- 25940258
TI  - A 19-year-old man with relapsing bilateral pneumothorax, hemoptysis, and
      intrapulmonary cavitary lesions diagnosed with vascular Ehlers-Danlos syndrome
      and a novel missense mutation in COL3A1.
AB  - A 19-year-old sportsman experienced a right-sided pneumothorax and hemoptysis
      after having had an intermittent cough and blood-tinged sputum for 2 months. A
      chest CT scan revealed small cavitary lesions in both lungs. The relapsing
      pneumothorax was treated with a chest tube twice, as well as surgically after the
      second relapse. Two months after surgery, the patient developed a cough, fever,
      and high C-reactive protein levels. At that time, large consolidations had
      developed in the right lung, while the left lung subsequently collapsed due to
      pneumothorax. The patient's physical appearance and anamnestic information led us
      to suspect a genetic connective tissue disease. A sequencing analysis of the
      COL3A1 gene identified a novel, de novo missense mutation that confirmed the
      diagnosis of vascular Ehlers-Danlos syndrome (EDS). This atypical presentation of
      vascular EDS with intrathoracic complications shows that enhanced awareness is
      required and demonstrates the usefulness of the genetic analyses that are
      clinically available for several hereditary connective tissue disorders. 

PMID- 25940259
TI  - A woman in her 50s with recent coronary artery bypass grafting presenting with
      right-sided chest pain.

PMID- 25940260
TI  - A rare cause of postoperative hypotension.
AB  - A 62-year-old woman presented with a 3-month history of abdominal distension and
      decreased exercise tolerance. A chest radiograph showed a probable left pleural
      effusion (Fig 1). A CT scan of the abdomen revealed a solid ovarian mass with
      omental caking and a large volume of ascites; there was also confirmation of a
      left pleural effusion. Three days before surgery a CT pulmonary angiogram (CTPA)
      showed no evidence of pulmonary thromboembolism (PTE). The patient had some
      improvement in her symptoms after paracentesis and thoracentesis with drainage of
      2,000 mL and 250 mL of fluid, respectively. She underwent total abdominal
      hysterectomy, bilateral oophorectomy, and partial sigmoid resection with an
      estimated blood loss of 850 mL. During the operation, she received 5 L of
      crystalloid and required phenylephrine at 40 to 80 MUg/min to maintain a mean
      arterial pressure > 65 mm Hg. She was extubated after surgery, but immediately
      after extubation, she became markedly hypotensive and hypoxemic with a BP of
      50/20 mm Hg and an oxygen saturation of 70%. An ECG showed T-wave inversions from
      V1 to V5 and an S1Q3T3 pattern (Fig 2). A bedside echocardiogram showed an
      enlarged right ventricle (RV), septal dyskinesia, and obliteration of the left
      ventricle, all consistent with systolic and diastolic RV overload (Fig 3). 

PMID- 25940261
TI  - A 44-year-old man with abdominal pain, lung nodules, and hemoperitoneum.
AB  - A 44-year-old man presented with a 1-day history of sudden-onset abdominal pain.
      The pain was characterized as severe, diffuse, sharp, and nonradiating.
      Associated symptoms included nausea, vomiting, diarrhea, and subjective fevers.
      He was originally from El Salvador, but had not traveled in > 10 years. Review of
      systems was positive for 2 weeks of dry cough with associated mild, bilateral,
      pleuritic chest pain and subjective weight loss. His medical history was notable
      for gout and end-stage renal disease secondary to chronic nonsteroidal
      antiinflammatory drug use, for which he attended hemodialysis sessions three
      times weekly. Surgical history consisted of a currently nonfunctioning left upper
      extremity fistula, a longstanding right internal jugular PermCath IV access for
      chronic hemodialysis that had been removed 2 weeks prior to presentation, and a
      left brachiocephalic fistula. He did not smoke, consume alcohol, or have a
      history of illicit drug use. 

PMID- 25940262
TI  - An unusual cause of respiratory failure in a 25-year-old heart and lung
      transplant recipient.
AB  - A 25-year-old woman, a never smoker with a history of heart-lung transplantation
      for World Health Organization group 1 pulmonary arterial hypertension performed
      20 months prior to presentation, was evaluated for shortness of breath. Following
      transplantation, she was initiated on standard therapy of prednisone, tacrolimus,
      and azathioprine, along with routine antimicrobial prophylaxis. Her
      posttransplant course was complicated by persistent acute cellular rejection, as
      determined from a transbronchial biopsy specimen, without evidence of rejection
      in an endomyocardial biopsy specimen. The immunosuppressive medications were
      supplemented with pulse-dosed steroids, and the patient was transitioned from
      azathioprine to mycophenolate mofetil. Sirolimus was added 9 months prior to
      presentation. Three months prior to presentation, she was admitted for increasing
      oxygen requirements, shortness of breath, and bilateral infiltrates on the CT
      scans of the chest. 

PMID- 25940263
TI  - Composite end points of death and hospitalization are the only appropriate option
      for most trials.

PMID- 25940264
TI  - Are CHEST guidelines global in coverage?: probably not.

PMID- 25940265
TI  - Response.

PMID- 25940266
TI  - Response.

PMID- 25940267
TI  - Double-lumen endotracheal tube device for percutaneous dilatational tracheostomy:
      an inventor's perspective.

PMID- 25940268
TI  - Response.

PMID- 25940269
TI  - Specific IgE is better than skin testing for detecting Aspergillus sensitization
      and allergic bronchopulmonary aspergillosis in asthma.

PMID- 25940270
TI  - The importance of considering safety data from large-scale clinical trials in
      patients with asthma.

PMID- 25940271
TI  - Response.

PMID- 25940272
TI  - Leptin and ventilation in heart failure.

PMID- 25940273
TI  - Response.

PMID- 25940274
TI  - Correlation between Dermatology Life Quality Index (DLQI) scores and Work
      Limitations Questionnaire (WLQ) allows the calculation of percent work
      productivity loss in patients with psoriasis.
AB  - Data on indirect costs are vital for cost-effectiveness studies from a societal
      perspective. In contrast to quality of life, information on productivity loss is
      rarely collected in psoriasis trials. We aimed to identify a model to deduce
      indirect costs (presenteeism and absenteeism) of psoriasis from the Dermatologic
      Life Quality Index (DLQI) of affected patients to facilitate health economic
      evaluations for psoriasis. We undertook a cross-sectional mapping study including
      201 patients with physician-diagnosed psoriasis and investigated the relationship
      between quality of life (DLQI) and productivity loss (Work Limitations
      Questionnaire, WLQ--using the "output demands" subscale) using linear bootstrap
      regression analysis to set up an equation model allowing the calculation of
      percent work productivity loss per DLQI unit increase. DLQI and WLQ scores were
      significantly correlated (r = 0.47; p < 0.0001) The final equation model suggests
      a 0.545 and 0.560% decrease in productivity due to presenteeism and absenteeism
      per DLQI unit increase, with y-intercepts at 1.654 and 0.536, respectively. In
      the absence of data on indirect cost, work productivity loss due to psoriasis can
      be estimated from DLQI scores using the equations, Y = 0.545 * DLQI score + 1.654
      for presenteeism (%) and Y = 0.560 * DLQI score + 0.536 for absenteeism (%).

PMID- 25940275
TI  - Validity of the mini-mental state examination and the montreal cognitive
      assessment in the prediction of driving test outcome.
AB  - OBJECTIVES: To evaluate the effectiveness of two cognitive screening measures,
      the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment
      (MoCA), in predicting driving test outcome for individuals with and without
      cognitive impairment. DESIGN: Retrospective cohort study. SETTING: A clinical
      driving evaluation program at a teaching hospital in the United States.
      PARTICIPANTS: Adult drivers who underwent assessment with the MMSE and MoCA as
      part of a comprehensive driving evaluation between 2010 and 2014 (N=92).
      MEASUREMENTS: MMSE and MoCA total scores were independent variables. The outcome
      measure was performance on a standardized road test. RESULTS: A preestablished
      diagnosis of cognitive impairment enhanced the validity of cognitive screening
      measures in the identification of at-risk drivers. In individuals with cognitive
      impairment there was a significant relationship between MoCA score and on-road
      outcome. Specifically, an individual was 1.36 times as likely to fail the road
      test with each 1-point decrease in MoCA score. No such relationship was detected
      in those without a diagnosis of cognitive impairment. CONCLUSION: For individuals
      who have not been diagnosed with cognitive impairment, neither the MMSE nor the
      MoCA can be reliably used as an indicator of driving risk, but for individuals
      with a preestablished diagnosis of cognitive impairment, the MoCA is a useful
      tool in this regard. A score on the MoCA of 18 or less should raise concerns
      about driving safety.

PMID- 25940276
TI  - Knowledge-guided docking: accurate prospective prediction of bound configurations
      of novel ligands using Surflex-Dock.
AB  - Prediction of the bound configuration of small-molecule ligands that differ
      substantially from the cognate ligand of a protein co-crystal structure is much
      more challenging than re-docking the cognate ligand. Success rates for cross
      docking in the range of 20-30 % are common. We present an approach that uses
      structural information known prior to a particular cutoff-date to make
      predictions on ligands whose bounds structures were determined later. The
      knowledge-guided docking protocol was tested on a set of ten protein targets
      using a total of 949 ligands. The benchmark data set, called PINC ("PINC Is Not
      Cognate"), is publicly available. Protein pocket similarity was used to choose
      representative structures for ensemble-docking. The docking protocol made use of
      known ligand poses prior to the cutoff-date, both to help guide the
      configurational search and to adjust the rank of predicted poses. Overall, the
      top-scoring pose family was correct over 60 % of the time, with the top-two pose
      families approaching a 75 % success rate. Correct poses among all those predicted
      were identified nearly 90 % of the time. The largest improvements came from the
      use of molecular similarity to improve ligand pose rankings and the strategy for
      identifying representative protein structures. With the exception of a single
      outlier target, the knowledge-guided docking protocol produced results matching
      the quality of cognate-ligand re-docking, but it did so on a very challenging
      temporally-segregated cross-docking benchmark.

PMID- 25940278
TI  - Characterization of Mononuclear Non-heme Iron(III)-Superoxo Complex with a Five
      Azole Ligand Set.
AB  - Reaction of O2 with a high-spin mononuclear iron(II) complex supported by a five
      azole donor set yields the corresponding mononuclear non-heme iron(III)-superoxo
      species, which was characterized by UV/Vis spectroscopy and resonance Raman
      spectroscopy. (1)H NMR analysis reveals diamagnetic nature of the superoxo
      complex arising from antiferromagnetic coupling between the spins on the low-spin
      iron(III) and superoxide. This superoxo species reacts with H-atom donating
      reagents to give a low-spin iron(III)-hydroperoxo species showing characteristic
      UV/Vis, resonance Raman, and EPR spectra.

PMID- 25940277
TI  - Does a decision aid for prostate cancer affect different aspects of decisional
      regret, assessed with new regret scales? A randomized, controlled trial.
AB  - OBJECTIVE: To develop and validate new regret scales and examine whether a
      decision aid affects different aspects of regret in the treatment choice for
      prostate cancer. METHODS: This was a multicentre trial (three sites) with
      imbalanced randomization (1 : 2). From 2008 to 2011, patients with localized
      prostate cancer were randomized 1 : 2 to usual care (N = 77) or usual care plus a
      decision aid presenting risks and benefits of different treatments (N = 163). The
      treatments were surgery and (external or interstitial) radiotherapy. Regret was
      assessed before, and 6 and 12 months after treatment, using the Decisional regret
      scale by Brehaut et al. (Medical Decision Making, 23, 2003, 281), and three new
      scales focusing on process, option and outcome regret. The relation between
      decision aid and regret was analysed by anova. RESULTS: The concurrent validity
      of the new regret scales was confirmed by correlations between regret and
      anxiety, depression, decision evaluation scales and health-related quality of
      life. With a decision aid, patient participation was increased (P = 0.002), but
      regret was not. If anything, in patients with serious morbidity the decision aid
      resulted in a trend to less option regret and less Brehaut regret (P = 0.075 and
      P = 0.061, with effect sizes of 0.35 and 0.38, respectively). Exploratory
      analyses suggest that high-risk patients benefitted most from the decision aid.
      CONCLUSION: The new regret scales may be of value in distinguishing separate
      aspects of regret. In general, regret was not affected by the decision aid. In
      patients with serious morbidity, a trend to lower option regret with a decision
      aid was observed.

PMID- 25940279
TI  - [The supernatant of 4T1 breast cancer cell culture increases arginase 1 content
      in ANA-1 macrophages].
AB  - OBJECTIVE: To explore the effect of the supernatant of 4T1 murine breast cancer
      cell culture on arginase 1 (Arg-1) in ANA-1 macrophages in vitro by simulating
      the microenvironment of breast cancer. METHODS: The experimental ANA-1
      macrophages were treated with the supernatant of 4T1 culture, and meanwhile, the
      control cells were cultured in the absence of the supernatant. Morphological
      changes of the ANA-1 macrophages were observed with a light microscope at 6, 8,
      10, 24 hours, respectively. Real-time quantitative PCR (qRT-PCR) was performed to
      detect the levels of inducible nitric oxide synthase (iNOS) and Arg-1 mRNAs.
      Immunofluorescence and Western blotting were used to determine the levels of iNOS
      and Arg-1 proteins. RESULTS: The qRT-PCR indicated that the level of iNOS mRNA
      decreased in the experiment group compared with the control group, while Arg-1
      mRNA level significantly increased compared with the control group and it reached
      a peak at the 8th hour. The immunofluorescence and Western blotting also
      demonstrated that Arg-1 protein expression was enhanced in the experimental group
      compared with the control group. However, iNOS protein expression was no
      significantly different between the experiment group and the control group.
      CONCLUSION: The supernatant of 4T1 cell culture increases Arg-1 production in ANA
      1 macrophages.

PMID- 25940280
TI  - [ApoE gene knockout causes high expressions of TNF-alpha, IL-1beta and IL-8 in
      mouse brain].
AB  - OBJECTIVE: To investigate the expression profile of tumor necrosis factor alpha
      (TNF-alpha), interleukin 1beta (IL-1beta) and IL-8 in the hippocampus and
      cerebral cortex of apolipoprotein E (ApoE) knockout (ApoE-/-) mice. METHODS:
      Twenty 4-week-old male mice were divided into 2 groups: wild-type mice and ApoE-/
      mice, 10 mice for each. After 12-week feeding, the blood sample was taken for
      serum lipid test and brain tissue were obtained for fixation and embedding. The
      histological changes of the hippocampus and cerebral cordex were observed by HE
      staining and the expressions of TNF-alpha, IL-1beta and IL-8 proteins were
      detected by immunohistochemistry. RESULTS: Compared with the wild-type mice, the
      numbers of the IL-1beta and IL-8-positive cells were markedly elevated in the
      hippocampus and cerebral cortex in ApoE-/- mice. The number of the TNF-alpha
      positive cells was markedly raised in the cerebral cortex after ApoE knockout,
      and the intensity of TNF-alpha positive substances in the hippocampus is higher
      in ApoE-/- mice than in wild-type mice. CONCLUSION: The expressions of IL-1beta
      and IL-8 in the brain increased after ApoE knockout in mice.

PMID- 25940281
TI  - [Sophoridine suppresses inflammatory cytokine secretion by lipopolysaccharide
      induced RAW264.7 cells and its mechanism].
AB  - OBJECTIVE: To observe the effects of sophoridine on lipopolysaccharide (LPS)
      induced secretion of tumor necrosis factor alpha (TNF-alpha) and interleukin
      1beta (IL-1beta) as well as the expressions of Toll-like receptor 4 (TLR4) and c
      Jun in RAW264.7 cells and explore the molecular mechanism of anti-LPS of
      sophoridine. METHODS: RAW264.7 cells were cultured and divided into four groups:
      macrophage control group (using serum-free DMEM to incubate cells), sophoridine
      control group (using 31.25 mg/L sophoridine-added DMEM to incubate cells), LPS
      group and sophoridine intervention group (using 100 MUg/L LPS DMEM to incubate
      cells for 60 minutes, then throwing away LPS and adding serum-free DMEM or 31.25
      mg/L sophoridine DMEM to incubate cells). Cells and culture medium were collected
      respectively at 5, 30, 60 and 120 minutes after the above treatment. The
      expression levels of TLR4 and c-Jun mRNA were determined by reverse transcription
      PCR (RT-PCR), and the expression of c-Jun protein in RAW264.7 cells was measured
      by immunocytochemistry and Western blotting; The levels of TNF-alpha and IL-1beta
      in cell culture medium were analyzed by ELISA. RESULTS: Compared with macrophage
      control group, sophoridine control group had no statistical difference in each
      index. Compared with macrophage control group, the expressions of TLR4 mRNA, c
      Jun mRNA and protein as well as the secretion of TNF-alpha and IL-1beta
      significantly increased at each time point in LPS group, and maintained the level
      to 120 minutes. Sophoridine suppressed the expressions of TLR4 mRNA, c-Jun mRNA
      and protein, and reduced the secretion of TNF-alpha and IL-1beta in LPS
      stimulated RAW264.7 cells in sophoridine intervention group. CONCLUSION:
      Sophoridine down-regulated the secretion of TNF-alpha and IL-1beta in LPS-induced
      RAW264.7 cells via inhibiting the expressions of TLR4 and c-Jun.

PMID- 25940282
TI  - [Resveratrol inhibits hyperxia-induced cell apoptosis through up-regulating SIRT1
      expression in HPAECs].
AB  - OBJECTIVE: To investigate the protection effect of sirtuin 1 (SIRT1) agonist
      resveratrol (Res) against the apoptosis of human pulmonary alveolar epithelial
      cells (HPAECs) induced by hyperxia. METHODS: The HPAECs in vitro were randomly
      divided into three groups: control group, hyperxia group, Res group. After 24
      hour culture, the expressions of caspase-9, X-linked inhibitor of apoptosis
      protein (XIAP), SIRT1 proteins were measured by SP immunohistochemistry. The
      changes of reactive oxygen species (ROS) marked with MitoSOX(TM) and membrane
      potential marked with JC-1 in mitochondrion were detected by laser scanning
      confocal microscopy. The expression of SIRT1 protein was determined by Western
      blotting, and the change of cell apoptosis rate was analyzed by flow cytometry
      combined with annexin V-FITC/PI staining. RESULTS: Compared with the control
      group, the expression of caspase-9, the generation of ROS in mitochondrion of
      HPAECs and the cell apoptosis rate increased obviously. The expressions of both
      XIAP and SIRT1 and membrane potential decreased evidently in the hyperxia group.
      Compared with the hyperxia group, the expression of caspase-9, the generation of
      ROS in mitochondrion of HPAECs and the cell apoptosis rate went down obviously.
      The expressions of XIAP and SIRT1, and the membrane potential went up evidently
      in the Res group. CONCLUSION: By up-regulating the expression of SIRT1 in of
      HPAECs and depressing the generation of ROS, Res inhibits the apoptosis of HPAECs
      and maintains the cell membrane potential, thus effectively alleviating hyperxia
      induced lung injury.

PMID- 25940284
TI  - [Newcastle disease virus enhances tumoricidal activity of mouse NK cells against
      mouse Novikoff hepatoma cells via up-regulating expression of TRAIL on the NK
      cells].
AB  - OBJECTIVE: To observe the effect of intraperitoneal injection of Newcastle
      disease virus (NDV) on tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL) expression in mouse spleen NK cells and NK cells-mediated tumoricidal
      activity against mouse Novikoff hepatoma cell line, and explore the role of
      interferon (IFN)-gamma in NDV-induced TRAIL expression and tumoricidal activity.
      METHODS: NDV was injected intraperitoneally to BALB/c mice and IFN-gamma receptor
      deficient (IFN-gammaR-/-) B6.129S7 mice. Twelve hours after injection, the
      concentration of IFN-gamma in peripheral blood from BALB/c mice was determined by
      ELISA. Mouse spleen NK cells were separated. The mRNA and protein expression of
      TRAIL in NK cells were detected through reverse transcription PCR (RT-PCR) and
      Western blotting. Lactate dehydrogenase (LDH) release assay was used to determine
      the cytotoxic activity of NK cells against mouse hepatoma cells. RESULTS: NDV
      injection increased the IFN-gamma concentration in peripheral blood of BALB/c
      mice, induced up-regulation of TRAIL at the mRNA and protein levels in mouse
      spleen NK cells, and enhanced the killing ability of mouse spleen NK cells
      towards Novikoff hepatoma cells. Blocking TRAIL by neutralizing antibody
      suppressed the cytotoxic activity of NK cells against Novikoff hepatoma cells.
      Furthermore, NDV injection in IFN-gammaR-/- B6.129S7 mice did not make
      significant difference from control group in TRAIL expression in spleen NK cells,
      and the tumoricidal activity of IFN-gammaR-/- B6.129S7 mouse spleen NK cells
      against Novikoff hepatoma cells was significantly lower than that of BALB/c mouse
      NK cells. CONCLUSION: Intraperitoneal injection with NDV could enhance
      tumoricidal activity of mouse spleen NK cells in vitro, and one of the mechanisms
      might be that NDV injection up-regulates TRAIL expression in NK cells through the
      IFN-gamma receptor pathway.

PMID- 25940283
TI  - [myc-p62 fusion protein suppresses the phosphorylation of extracellular signal
      regulated kinase].
AB  - OBJECTIVE: To construct a eukaryotic expression vector of human autophagy maker
      protein P62 labeled with myc tag, and detect its biological function. METHODS:
      Human P62 gene was amplified from human breast DNA library by PCR and cloned into
      pXJ-40-myc vector. HEK293T cells were transfected with the recombinant plasmid
      myc-p62. Western blotting was conducted to detect the fusion protein expression
      and the effect on the phosphorylation of extracellular signal-regulated kinase
      (ERK). RESULTS: Double enzyme identification and sequencing result showed that
      P62 eukaryotic expression vector labeled with myc tag was successfully
      constructed and the inserted fragment was correct. Western blotting indicated
      that the fusion protein was successfully expressed and was able to inhibit ERK
      phosphorylation. CONCLUSION: The eukaryotic expression vector of myc-p62 was
      successfully constructed and proved to have an inhibitory effect on ERK
      phosphorylation.

PMID- 25940285
TI  - [Lentivirus-mediated shRNA silencing of LAMP2A inhibits the proliferation of
      multiple myeloma cells].
AB  - OBJECTIVE: To study the effects of lentivirus-mediated short hairpin RNA (shRNA)
      silencing of lysosome-associated membrane protein type 2A (LAMP2A) expression on
      the proliferation of multiple myeloma cells. METHODS: The constructed shRNA
      lentiviral vector was applied to infect human multiple myeloma cell line MM.1S,
      and stable expression cell line was obtained by puromycin screening. Western
      blotting was used to verify the inhibitory effect on LAMP2A protein expression.
      MTT assay was conducted to detect the effect of knocked-down LAMP2A on MM.1S cell
      proliferation, and the anti-tumor potency of suberoylanilide hydroxamic acid
      (SAHA) against the obtained MM.1S LAMP2A(shRNA) stable cell line. Lactate assay
      was performed to observe the impact of low LAMP2A expression on cell glycolysis.
      RESULTS: The stable cell line with low LAMP2A expression were obtained with the
      constructed human LAMP2A-shRNA lentiviral vector. Down-regulation of LAMP2A
      expression significantly inhibited MM.1S cell proliferation and enhanced the anti
      tumor activity of SAHA. Interestingly, decreased LAMP2A expression also inhibited
      MM.1S cell lactic acid secretion. CONCLUSION: Down-regulation of LAMP2A
      expression could inhibit cell proliferation in multiple myeloma cells.

PMID- 25940286
TI  - [Comparison of immunosuppressive effects between human placental MSCs derived
      from fetal and maternal origins on the rejection of allogenic skin grafts in
      mice].
AB  - OBJECTIVE: To compare the immunosuppressive effects of maternal and fetal
      placental mesenchymal stem cells (mPMSCs and fPMSCs, respectively) on the
      rejection of allogenic skin transplants in mice, and further to investigate the
      mechanism underlying this suppression. METHODS: The mPMSCs and fPMSCs were
      isolated from human term placentas. The expressions of cell surface markers were
      detected by flow cytometry. Cell proliferation capacity was characterized by MTT
      colorimetric assay. CD200 protein expressed on fPMSCs was neutralized with
      streaming monoclonal antibodies, and mPMSCs were infected with adenovirus
      expression vector carrying CD200 cDNA. For skin transplantation, 60 C57BL/6 mice
      were randomly divided into 6 groups as skin transplant recipients, and ICR mice
      served as skin donors. After establishment of the allogenic skin transplants,
      recipient mice of the 6 groups were intravenous injected respectively with PBS,
      mPMSCs, fPMSCs, fPMSCs combined with anti-CD200 antibodies, mPMSCs with CD200
      expressing vectors, and mPMSCs with empty vectors. The conditions and survival
      time of the skin grafts were inspected daily, and the expressions of interleukin
      17 (IL-17), interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha)
      and interleukin 12 (IL-12) in blood and spleen were measured at the end of the
      study by ELISA and reverse transcription PCR. RESULTS: The majority (>70%) of
      fPMSCs were detected CD200 positive, while only a minor fraction (about 2%) of CD
      200 positive cells were seen in mPMSCs. In the allogenic skin graft mice, the
      graft survival time in both mPMSCs- and fPMSCs-treated groups were significantly
      longer than that in PBS group [(5.6+/-1.17) days], while the fPMSCs group
      [(10.6+/-1.43) days] was more dominant than mPMSCs group [(7.7+/-1.42) days].
      Neutralizing anti-CD200 antibody reduced the graft survival [(8.2+/-1.14) days]
      of the fPMSCs group to the level of that in mPMSCs group, while enforced
      expression of CD200 increased the graft survival [(10.7+/-1.34) days] of the
      mPMSCs group to the level of the fPMSCs group. The empty vector-transfected
      mPMSCs showed a similar effect on graft survival [(7.8+/-1.32) days] as that in
      mPMSCs group, longer than PBS group but shorter than fPMSCs and mPMSCs combined
      with CD200 groups. Comparing with PBS group, the expressions of IL-17, IFN-gamma
      and TNF-alpha were significantly reduced in mPMSCs and fPMSCs groups. The
      reduction of these cytokine expressions in the fPMSCs group was neutralized when
      anti-CD200 antibody was applied, while this reduction in the mPMSCs-treated mice
      was further enhanced when the mPMSCs were enforced to express CD200. CONCLUSION:
      The immunosuppressive effect of fPMSCs on the rejection of allogenic skin
      transplantation was higher than that of mPMSCs, and this difference was partially
      contributed by CD200 signaling pathway. The mechanism of this suppression may
      mediate the inhibition of IL-17, IFN-gamma, TNF-alpha and IL-12 expressions. The
      fPMSCs may be a suitable choice for immunosuppression on skin transplantation.

PMID- 25940287
TI  - [Rhein promotes the expression of SIRT1 in kidney tissues of type 2 diabetic
      rat].
AB  - OBJECTIVE: To observe the effect of rhein on the expression of SIRT1(Sirtuin 1)
      in kidney of diabetic rats, and to explore the role of rhein in protecting rat
      kidney against diabetic nephropathy and possible mechanism. METHODS: The type 2
      diabetic rats were induced by high-glucose and high-fat diet combined with
      streptozotocin (35 mg/kg body mass). Seventy-five eight-week-old male SD rats
      were randomly divided into 6 groups: normal group, diabetic group, low-, medium-
      and high-dose (50, 100, 150 mg/kg) rhein treatment groups and 10 mg/kg
      pioglitazone treatment group. The rats were given corresponding substances
      intragastrically once a day. At the end of the 16th week, the fasting plasma
      glucose (FPG), fasting insulin (FINS), triglycerides (TG), total cholesterol
      (TC), serum creatinine (Scr) and 24 hours urine protein (24 h U-PRO) were
      determined. The renal hypertrophy index (KM/BM), insulin resistance index (HOMA
      IR) were calculated. The pathological changes in renal tissues were examined by
      PAS staining under a light microscopy. The mean glomerular area (MGA) and mean
      glomerular volume (MGV) were measured by pathological image analysis system.
      Western blotting and real-time quantitative PCR were used to determine the
      expression of SIRT1 in renal tissues at protein and mRNA levels, respectively.
      RESULTS: The expression of SIRT1 was down-regulated in the kidney of diabetic
      rats. The levels of FPG, FINS, HOMA-IR, TG, TC, Scr, 24 h U-PRO, KM/BM, MGA and
      MGV significantly decreased and the histopathology of renal tissues were
      significantly improved in all treatment groups compared with diabetic group. The
      expression of SIRT1 mRNA and protein markedly increased in rhein treatment groups
      and pioglitazone treatment group compared with diabetic group. The indicators in
      high-dose rhein treatment group were improved more significantly than those in
      the other groups. Correlation analysis showed that the expression of SIRT1 was
      negatively correlated with 24 h U-PRO and MGV. CONCLUSION: The expression of
      SIRT1 was reduced in kidney tissues of diabetic rats. Rhein could attenuate
      kidney damage in diabetic rats by improving the insulin resistance and
      dyslipidemia, and increasing the SIRT1 expression.

PMID- 25940288
TI  - [Emodin worsens methionine-choline-deficient diet-induced non-alcoholic fatty
      liver disease in mice].
AB  - OBJECTIVE: To investigate the influence of emodin on methionine-choline-deficient
      (MCD) diet-induced non-alcoholic fatty liver disease (NAFLD) in mice. METHODS:
      C57BL/6J mice were randomly divided into three groups: methionine-choline
      supplemented (MCS) diet group, MCD diet plus DMSO injection group (MCD), MCD diet
      plus emodin injection group (MCD-emodin). The mice were fed with MCS or MCD diet
      for 10 days, and then peritoneally injected with DMSO or emodin for 20 days
      consecutively. HE staining was performed to observe pathologic changes of livers.
      The levels of serum alanine aminotransferase (ALT) and aspartate transaminase
      (AST), triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL),
      low density lipoprotein (LDL), alkaline phosphatase (ALP), glucose (GLU) were
      measured by automatic biochemical analyzer. The mRNA levels of interleukin 1beta
      (IL-1beta), IL-6 and tumor necrosis factor-alpha (TNF-alpha) were determined by
      real-time quantitative PCR. RESULTS: HE staining showed that there were more
      lipid accumulation and leukocyte infiltration in the livers of the MCD group
      compared with the MCS group. The above manifestations were more severe in the MCD
      emodin group. Moreover, compared with the MCD group, emodin injection remarkably
      raised serum AST and ALT levels and greatly increased IL-1beta and IL-6 mRNA
      levels. CONCLUSION: Emodin worsened MCD diet-induced NAFLD in mice.

PMID- 25940289
TI  - [Increased expression of acetaldehyde dehydrogenase in cisplatin-resistant human
      lung adenocarcinoma A549/DDP cells].
AB  - OBJECTIVE: To investigate the expression and biological significance of
      acetaldehyde dehydrogenase (ALDH) in cisplatin-resistant human A549/DDP lung
      adenocarcinoma cell line. METHODS: The expressions of biomarkers of cancer stem
      cells (CSCs) including CD44, CD73, CD90, CD105, epithelial cell adhesion molecule
      (EpCAM), ATP-binding cassette sub-family G member 2 (ABCG2) and ALDH in human
      lung adenocarcinoma A549 cells and cisplatin-resistant A549/DDP cells were
      ascertained by flow cytometry. The proliferation and sensitivity of A549/DDP
      cells to cisplatin were evaluated by MTT assay before and after ALDH inhibitor
      diethylaminobenzaldehyde (DEAB) treatment. The differential expression of ALDH
      subtypes in cells was determined by real-time quantitative PCR, and was further
      confirmed by a Western blotting. RESULTS: The frequencies of ABCG2 and ALDH
      positive cells were higher in cisplatin-resistant A549/DDP cells than those in
      A549 cells, in particular the expression of ALDH which was 97.7% in A549/DDP
      cells, and only 4.3% in A549 cells. There was no significantly differential
      expression of CD44, CD90, CD73, CD105 between A549/DDP cells and A549 cells,
      whereas less EpCAM was found in A549/DDP cells compared with A549 cells.
      Importantly, the ALDH inhibitor DEAB (100 MUmol/L) was able to significantly
      reduce cisplatin resistance in A549/DDP cells. Compared with A549 cells, the
      expressions of ALDH subtypes ALDH1A3 and ALDH1B1 mRNA significantly went up in
      A549/DDP cells. Interestedly, Western blotting revealed that ALDH1B1 protein
      expression was elevated but ALDH1A3 protein was reduced in A549/DDP cells in
      comparison with A549 cells. CONCLUSION: ALDH can serve as a useful surface marker
      for cisplatin-resistant human lung adenocarcinoma cells.ALDH1B1 may play a role
      in the chemoresistance of these cells. Therefore, ALDH1B1 may be an important
      target for developing novel therapeutic agents and strategies for patients with
      cisplatin-resistant lung adenocarcinoma.

PMID- 25940290
TI  - [Cigarette smoke extract induces senescence of murine skeletal muscle cells by
      oxidative stress-induced down-regulation of histone deacetylase 2].
AB  - OBJECTIVE: To investigate whether cigarette smoke extract (CSE) induces the
      senescence of skeletal muscle cells by oxidative stress-induced down-regulation
      of histone deacetylase 2 (HDAC2). METHODS: C2C12 myoblasts were induced to
      differentiate into skeletal muscle cells. H2O2 and N-acetyl cysteine (NAC) were
      used to investigate the effects of CSE on oxidative stress, cell senescence and
      the expression of HDAC2 in skeletal muscle cells, and detect the changes of the
      activities of malondialdehyde (MDA), superoxide dismutase (SOD), reactive oxygen
      species (ROS) and glutathione peroxidase (GSH-Px). Cell senescence was identified
      by senescence-associated beta-galactosidase staining. The expressions of HDAC2
      mRNA and protein were measured by real-time quantitative PCR and Western
      blotting, respectively. RESULTS: Compared with the control group, MDA
      concentration and ROS activity significantly increased, the activities of SOD and
      GSH-Px significantly decreased, the expression of beta-galactosidase was up
      regulated, and the expressions of HDAC2 mRNA and protein were down-regulated in
      the CSE group and the H2O2 group. However, the changes in the CSE group were
      reversed after the pretreatment of NAC. CONCLUSION: CSE may lead to the
      senescence of murine skeletal muscle cells by oxidative stress-induced down
      regulation of HDAC2.

PMID- 25940291
TI  - [Myocardial oxidative stress injury and myocardial ultrastructure in septic
      rats].
AB  - OBJECTIVE: To investigate the mechanism of myocardial injury in septic rats by
      cecal ligation and puncture. METHODS: Fifty-four male Sprague-Dawley (SD) rats
      were randomly divided into 3 groups: normal group (n=6), sham group (n=24),
      sepsis group (n=24). Cecal ligation and puncture (CLP) was adopted to reproduce
      animal models of sepsis. The contents of cardiac troponin I (cTnI) and nitric
      oxide (NO) in serum and the activities of superoxide dismutase (SOD) and
      malondialdehyde (MDA) in myocardium were detected in each group 3, 6, 12, 24
      hours after the operation (with 6 rats at each time point). The changes of
      myocardial pathomorphology were observed by HE staining under a microscope. The
      ultrastructural changes of myocardial cells were observed by the electron
      microscopy. RESULTS: The levels of serum cTnI and NO in the sepsis group were
      much higher than those in the sham group and the normal group. At the same time,
      the activity of MDA in myocardium in the sepsis group was also significantly
      higher than that in the other two groups. While the activity of SOD was obviously
      lower. Besides, ultrastructural changes in sepsis ones included myocardial cell
      edema, inflammatory cell infiltration, interstitial angiectasis and hyperemia and
      visible focal myocardial necrosis. Myocardial cell injury was more serious in
      sepsis rats compared with the other two groups. Electron microscopy showed
      different degrees of disorganized myofibrils, widened intercalated disc gap,
      decreased mitochondrial cristae and vacuolation of myocardium in sepsis group.
      CONCLUSION: The myocardial cell injury is due to oxidative stress injury in
      septic rats. As the disease progresses, the myocardial ultrastructure damage
      becomes worse gradually.

PMID- 25940292
TI  - [Hypoxia and hyperglycemia promote the proliferation and migration of human
      marrow mesenchymal stem cells in vitro].
AB  - OBJECTIVE: To investigate the cell proliferation, apoptosis and migration of
      human marrow mesenchymal stem cells (hMSCs) under hypoxia and hyperglycemia.
      METHODS: The hMSCs from healthy adults were isolated and harvested by density
      gradient centrifugation followed by adherent cultures. The cells was divided into
      four groups: control group (210 mL/L O2 with 5.56 mmol/L glucose), high glucose
      and normoxia group (210 mL/L O2 with 30 mmol/L glucose), normal glucose and
      hypoxia group (50 mL/L O2 with 5.56 mmol/L glucose) and high glucose and hypoxia
      group (50 mL/L O2 with 30 mmol/L glucose). The cells at the third passage were
      cultured in different groups. Then, we used cell counting kit-8 (CCK-8) to detect
      the proliferation of hMSCs, Transwell(TM) assay to examine the migration of
      hMSCs, and flow cytometry to observe the apoptosis of hMSCs at 24 hours. RESULTS:
      Compared with the control group, the proliferation rate of hMSCs increased in the
      other groups at 24 and 48 hours, and the maximum proliferation effect was found
      in high glucose and hypoxia group. Compared with the control group, the migration
      ability of hMSCs in the other groups was enhanced dramatically at 24 hours,
      whereas there was no significant difference in the apoptosis rate among the four
      groups. CONCLUSION: Both high glucose and hypoxia could improve the migration and
      proliferation of hMSCs, but they have no effect on apoptosis.

PMID- 25940293
TI  - [Establishment of C26 cell strain stably expressing folate receptor alpha].
AB  - OBJECTIVE: To establish a C26 cell strain stably expressing folate receptor alpha
      (FRalpha) for the subsequent study of FRalpha DNA vaccine. METHODS: C26 cells
      were transfected with previously constructed recombinant eukaryotic expressing
      vector pcDNA3.1-FRalpha by LipofectamineTM2000. Afterwards the cells were
      subjected to G418 (500 mg/mL) selection to get G418 resistant cells. And then
      single cell cloning was performed to generate monoclonal cell strain. The gene
      and protein expression levels of FRalpha of the monoclonal cell strain were
      further analyzed by reverse transcription PCR (RT-PCR) and fluorescence
      microscopy. The cells were cultured for several generations, and the mRNA
      expression of FRalpha was analyzed by RT-PCR at different generations to
      determine whether the transfected gene was stable or not during cell passaging.
      RESULTS: After transfection, G418 selection and single cell cloning, the
      monoclonal cell strain were established and proved to be able to express FRalpha
      mRNA and protein and keep the stability of FRalpha expression after several
      generations. CONCLUSION: We have established the cell strain stably expressing
      FRalpha, which offer a tool to evaluate the effect of DNA vaccine based on
      FRalpha.

PMID- 25940294
TI  - [Development and assessment of a chemiluminescence assay kit for detecting anti
      HEV IgG].
AB  - OBJECTIVE: To develop an anti-hepatitis E virus (anti-HEV) IgG chemiluminescence
      assay kit and assess its clinical application. METHODS: The HEV recombinant
      antigen was used as coating antigen, horseradish peroxidase (HRP)-conjugated
      monoclonal anti-human IgG as the secondary antibody, and the luminol
      chemiluminescent reaction system as a substrate. The sensitivity, specificity,
      precision and other technical indicators of the kit were evaluated using the HEV
      national reference product, and a contrast experiment was conducted on 1012 serum
      samples by the kit developed in this research and a commercialized anti-HEV IgG
      chemiluminescence assay kit. RESULTS: The sensitivity, specificity, precision and
      stability of all the three batches of kit reached national standard. In the
      detection of 1012 clinical serum samples, the positive coincidence rate of both
      kits was 97.4%, the negative coincidence rate was 99.4%, and the total
      coincidence rate reached 98.4%. CONCLUSION: An anti-HEV IgG chemiluminescence
      assay kit has been successfully developed. The kit is of high sensitivity and
      specificity, easy to operate. It is applicable to the clinical diagnosis and
      epidemiological survey of HEV infection.

PMID- 25940295
TI  - [Antitumor effect of low-voltage electric pulses on melanoma-bearing mice].
AB  - OBJECTIVE: To investigate the antitumor effect of the low-voltage electric pulses
      (LVEPs) on melanoma-bearing mice. METHODS: Tumor models were established by
      subcutaneously inoculating BALB/c mice with B16F10 melanoma cells. These mice
      were randomly divided into control group and treated groups which were exposed to
      electric pulses of different frequency 10, 20, 30 Hz for consecutive 20 days with
      30 minutes per day. In every day, tumor size was measured, and morphological
      changes of tumors were observed by HE staining. The expressions of caspase-3 and
      matrix metalloproteinase-9 (MMP-9) mRNAs were tested by real-time quantitative
      PCR, and the expressions of caspase-3 and MMP-9 proteins were detected by
      immunohistochemistry. RESULTS: Compared with the control group, seven days after
      LVEPs treatment, the tumor size in 30Hz treated group was reduced significantly;
      twenty days after treatment, the tumor size of all treated groups diminished
      significantly. The tumor growth inhibition rate increased with time. Compared
      with the control group, nuclear shrinkage and necrosis of more tumor cells were
      found in the treated groups; the expression of caspase-3 mRNA and protein was
      significantly enhanced in the treated groups; the expression of MMP-9 mRNA and
      protein was significantly depressed in the treated groups; and the changes of
      caspase-3 and MMP-9 expressions became greater with the frequency increasing.
      CONCLUSION: LVEPs can induce the activation of caspase-3, suppress the expression
      of MMP-9, and inhibit tumor growth.

PMID- 25940296
TI  - [Down-expression of FOXA2 in gastric adenocarcinoma].
AB  - OBJECTIVE: To investigate the expression of FOXA2 in human gastric adenocarcinoma
      and its correlation with cell migration and invasion. METHODS: Fifty-six pairs of
      gastric adenocarcinoma and matched tumor-adjacent tissues were freshly collected.
      The expressions of FOXA2 and epithelial cadherin (E-cadherin) in the gastric
      specimens were detected using immunohistochemistry. Western blotting was
      performed to test FOXA2 and E-cadherin expressions in different gastric cancer
      cell lines. FOXA2 was over-expressed in MKN-45 cells. TranswellTM assays were
      performed to observe gastric cancer cell migration and invasion in vitro.
      Spearman rank correlation coefficient was used for correlation analysis. RESULTS:
      The expressions of FOXA2 and E-cadherin in gastric adenocarcinoma were
      significantly lower than those in matched tumor-adjacent noncancerous tissues.
      FOXA2 was positively correlated with E-cadherin expression in gastric
      adenocarcinoma tissues. Clinical analysis suggested that FOXA2 expression was
      prominently associated with tumor differentiation, infiltration depth, lymph node
      metastasis and TNM stage, respectively. The lowest expressions of FOXA2 and E
      cadherin were found in highly invasive gastric cancer MKN-45 cell line; the
      highest expressions of FOXA2 and E-cadherin were observed in low metastatic
      gastric cancer N-87 cell line. Over-expression of FOXA2 significantly increased
      the expression of E-cadherin protein and obviously inhibited cell migration and
      invasion in MKN-45 cells. CONCLUSION: Expression of FOXA2 is reduced in gastric
      adenocarcinoma tissues and its low-expression is correlated with malignant
      clinical pathological features. Over-expression of FOXA2 in MKN-45 cells up
      regulates E-cadherin expression and inhibits gastric cancer cell migration and
      invasion.

PMID- 25940297
TI  - [Down-regulated expression of c-Jun in peripheral blood mononuclear cells of
      patients with severe secondary pulmonary tuberculosis].
AB  - OBJECTIVE: To compare the expression of c-Jun in severe versus mild secondary
      pulmonary tuberculosis (TB) and understand the relationship of the c-Jun
      expression with the inflammation and immune injury of severe secondary TB
      patients. METHODS: Differentially expressed genes were screened in patients with
      severe TB, the ones with mild TB and healthy controls using Affymetrix human gene
      expression chips. Bioinformatic analysis was performed on the results of the gene
      chip screening. The relative transcript level of c-Jun was detected by real-time
      quantitative PCR (qRT-PCR). The protein expression of c-Jun in peripheral blood
      mononuclear cells was detected by ELISA. RESULTS: Patients with severe pulmonary
      TB exibited a large number of differentially expressed genes compared with
      healthy controls and patients with mild secondary TB, and these differential
      expressed genes involved complicated pathways of immue response and inflammation.
      C-Jun was down-regulated 2.27 times in the patients with severe secondary TB
      compared with the ones with mild TB, and it is involved in 61 pathways. The qRT
      PCR verified that c-Jun was down-regulated significantly in the patients with
      severe secondary TB compared with the mild ones. ELISA confirmed the trend of
      down-regulation of c-Jun in the patients with severe secondary TB. The results of
      qRT-PCR and ELISA were consistent with gene chip analysis. CONCLUSION: C-Jun was
      down-regulated in the patients with severe secondary TB compared with the
      patients with mild TB, and it is involved in many pathways of immue response and
      inflammation. Its down-regulation might be related to the immune injury of severe
      secondary TB.

PMID- 25940298
TI  - [Impaired apoptosis of peripheral blood CD4+T cells in patients with rheumatoid
      arthritis].
AB  - OBJECTIVE: To investigate the role of CD4+T cell apoptosis in the pathogenesis of
      rheumatoid arthritis (RA). METHODS: The study enrolled 30 RA cases and 12 normal
      individuals as subjects. The apoptosis level of CD4+T lymphocytes in the patients
      with RA and the control individuals were measured by annexin V-FITC/PI staining
      combined with flow cytometry. The expression levels of Fas, FasL, caspase-8,
      caspase-3, Bcl-2 and Bax mRNAs were detected using real-time quantitative PCR
      (qRT-PCR); the expressions of Fas, FasL, caspase-8, caspase-3 proteins were
      observed using Western blotting. The correlations between the expressions of the
      apoptosis-related proteins and the clinical activity parameters were analyzed.
      RESULTS: The apoptosis level of CD4+T lymphocytes in RA patients was
      significantly lower than that in the healthy controls, and it was negatively
      correlated with erythrocyte sedimentation rate (ESR) and rheumatoid factor (RF).
      Compared with the healthy control group, the expression levels of Fas, FasL,
      caspase-8, caspase-3 and Bax mRNAs in CD4+T cells of the RA patients were
      significantly reduced, whereas Bcl-2 mRNA was significantly elevated. The
      expression of Fas mRNA in CD4+T cells was negatively correlated with traditional
      Chinese medicine symptom score, whereas Bcl-2 mRNA was positively correlated with
      cyclic citrullinated peptide (CCP). Compared with the control group, the
      expressions of Fas, FasL, caspase-8 and caspase-3 proteins in CD4+T cells in the
      RA patients significantly decreased. The expression level of Fas protein was
      positively correlated with C-reactive protein (CRP), whereas FasL was negatively
      correlated with the time of morning stiffness. CONCLUSION: There is a decrease in
      the apoptosis of peripheral blood CD4+T cells in patients with RA, which has been
      found related to the decreased expressions of the apoptosis-related proteins
      (Fas, FasL, caspase-8, caspase-3, Bax) and the increased expression of Bcl-2. The
      study suggests that Fas-mediated apoptosis plays a role in the development of RA.

PMID- 25940299
TI  - [Preparation and identification of polyclonal antibodies against CUB1 and CUB2
      functional domains from mannan-binding lectin-associated serine protease-2].
AB  - OBJECTIVE: To express CUB1 and CUB2 functional domain proteins of mannan-binding
      lectin-associated serine protease-2 (MASP-2) by prokaryotic expression system,
      and further prepare and identify the polyclonal antibodies against these two
      domains. METHODS: The pGEX-6P-2 prokaryotic vector carrying the target gene CUB1
      and CUB2 was used to prepare the recombinant protein GST-CUB1 and GST-CUB2. These
      two fusion proteins were purified with Glutathione SepharoseTM4B beads and then
      combined with Freund's adjuvant as antigens to immunize the BALB/c female mice
      aged 5 weeks for generating polyclonal antibodies. Subsequently, the specificity
      of the polyclonal antibodies was detected by Western blotting, and the titer was
      determined by indirect ELISA. RESULTS: The fusion proteins GST-CUB1 and GST-CUB2
      were successfully expressed and purified. Their polyclonal antibodies were gained
      from the BALB/c mice immunized with these two proteins. The polyclonal antibodies
      showed high specificity with no cross-reaction with other proteins. Indirect
      ELISA indicated that the titer of anti-CUB1 antibody was more than 1:32 000 and
      anti-CUB2 antibody was more than 1:16,000. CONCLUSION: The polyclonal antibodies
      against GST-CUB1 and GST-CUB2 fusion proteins were obtained respectively with
      high titers and strong specificity.

PMID- 25940300
TI  - Dual Enzyme-Responsive Capsules of Hyaluronic Acid-block-Poly(Lactic Acid) for
      Sensing Bacterial Enzymes.
AB  - The synthesis of novel amphiphilic hyaluronic acid (HYA) and poly(lactic acid)
      (PLA) block copolymers is reported as the key element of a strategy to detect the
      presence of pathogenic bacterial enzymes. In addition to the formation of defined
      HYA-block-PLA assemblies, the encapsulation of fluorescent reporter dyes and the
      selective enzymatic degradation of the capsules by hyaluronidase and proteinase K
      are studied. The synthesis of the dual enzyme-responsive HYA-b-PLA is carried out
      by copper-catalyzed Huisgen 1,3-dipolar cycloaddition. The resulting copolymers
      are assembled in water to form vesicular structures, which are characterized by
      scanning electron microscopy, transmission electron microscopy, dynamic light
      scattering (DLS), and fluorescence lifetime imaging microscopy (FLIM). DLS
      measurements show that both enzymes cause a rapid decrease in the hydrodynamic
      diameter of the nanocapsules. Fluorescence spectroscopy data confirm the
      liberation of encapsulated dye, which indicates the disintegration of the
      capsules and validates the concept of enzymatically triggered payload release.
      Finally, cytotoxicity assays confirm that the HYA-b-PLA nanocapsules are
      biocompatible with primary human dermal microvascular endothelial cells. 

PMID- 25940301
TI  - Association between systemic oxidative stress and insulin resistance/sensitivity
      indices - the PREDIAS study.
AB  - OBJECTIVE: Systemic oxidative stress has been causally related to insulin
      resistance and the subsequent development of type 2 diabetes mellitus (T2D). We
      investigated associations between circulating oxidative stress markers and
      different surrogate indexes of insulin sensitivity/resistance. PATIENTS: Cross
      sectional data were obtained from 1183 subjects with normal glucose tolerance
      (NGT), 280 subjects with impaired glucose tolerance (IGT) and 69 newly detected
      T2D individuals entering the PREDIAS (prevention of diabetes) study.
      MEASUREMENTS: Following oral glucose tolerance test, five different insulin
      sensitivity/resistance indices were estimated: homoeostasis model of insulin
      resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI),
      early phase insulin release (EPIR), insulin sensitivity index (ISI) and
      disposition index (DI). Additionally, circulating phagocyte generation of
      reactive oxygen species (ROS) and plasma total antioxidant capacity (TAC) was
      measured. RESULTS: After adjustment for five covariates, HOMA-IR was
      significantly increased in IGT and T2D subjects when compared to NGT subjects (P
      = 0.000). QUICKI (P = 0.000), ISI (P = 0.000), EPIR (0.005/0.012) and DI (P =
      0.000) were significantly attenuated in IGT and T2D. The prevalence of IGT and
      T2D individuals increased with increasing ROS generation and TAC tertiles.
      Increased systemic ROS generation was paralleled by increased HOMA-IR (P < 0.001,
      tertile 1/T1/vs tertile 3/T3/), decreased QUICKI (P < 0.001, T1 vs T3) and
      decreased ISI (P < 0.05, T1 vs T3). A similar tendency for indices was observed
      when comparing TAC tertiles: increase in HOMA-IR, decrease in QUICKI and ISI (P <
      0.001, T1 vs T3 each). EPIR and DI did not differ significantly across ROS
      generation and TAC tertiles. CONCLUSIONS: Systemic oxidative stress is associated
      with elevated insulin resistance index HOMA-IR, and decreased insulin sensitivity
      surrogates QUICKI and ISI.

PMID- 25940302
TI  - Prevalence of potentially inappropriate medicine use in older New Zealanders: a
      population-level study using the updated 2012 Beers criteria.
AB  - RATIONAL, AIMS AND OBJECTIVES: To examine the prevalence of potentially
      inappropriate medicines (PIMs) in older New Zealanders at a population level.
      METHODS: De-identified prescription data for all individuals >=65 years were
      obtained from the Pharmaceutical Claims Data Mart for 2011. International
      Classification of Diseases-10-AM (version 6) codes were used to extract
      diagnostic information from the National Minimum Datasets and PIMs were
      identified using the updated Beers 2012 criteria. RESULTS: 40.9% of older people
      were prescribed PIMs with approximately half dispensed >=2 PIMs in 2011. Exposure
      was highest in individuals aged 65-74 years (68.9 +/- 2.9). The most prevalent
      PIMs dispensed were diclofenac (6.0%), amitriptyline (4.9%), ibuprofen (4.6%),
      zopiclone (3.2%) and naproxen (3.0%). 66.3% of individuals were dispensed >=1 and
      80.8% were dispensed >=2 medicines with a potential for drug-disease/syndrome
      interaction. CONCLUSIONS: The updated Beers 2012 criteria identified that the use
      of PIMs at a population level is common in older New Zealanders.

PMID- 25940303
TI  - Commentary on the medico-legal aspects of prescribing vitamin D.

PMID- 25940304
TI  - Influence of Psoriasis on Household Chores and Time Spent on Skin Care at Home: A
      Questionnaire Study.
AB  - INTRODUCTION: Previous studies have shown that psoriasis has a significant effect
      on patients' health-related quality of life. The impact of psoriasis on household
      chores and the need for assistance with such tasks are not well documented. The
      aim of this study was to estimate the impact of psoriasis on the ability to carry
      out household chores, the time spent on skin care at home and the assistance that
      patients with psoriasis require with these activities. METHODS: In a
      questionnaire study 262 patients with moderate-to-severe psoriasis, visiting a
      tertiary level dermatological clinic during a 1-year study period, listed
      household chores which they considered were particularly affected by psoriasis.
      This was done without a predefined list of chores. Questions on their ability to
      perform household chores as well as time spent on skin care at home were asked.
      The need for outside assistance with household chores and help received were also
      determined. RESULTS: More than half of the patients (57.8%) reported difficulties
      with household chores because of psoriasis. Psoriasis affected a wide range of
      everyday household activities, with physically demanding tasks and those
      involving contact with water mentioned most often. Most of the patients (84.6%)
      reported that they have increased the time spent on skin care because of
      psoriasis, on average by 87 min per week. A quarter of patients received
      assistance in household chores. Women received more assistance than men (p <
      0.01). The need for additional assistance was reported by a fifth of patients,
      women more often than men (p < 0.05). CONCLUSION: When estimating the overall
      burden of psoriasis, considering only the economic and productivity consequences
      may underestimate the impact of the disease. The impact on everyday life events
      such as the ability to perform household chores should also be taken into
      account. FUNDING: This study was supported by unconditional grants from the
      research funds of the Hospital District of Southwest Finland. Hospital District
      of Southwest Finland's research permission K44/10/EVO13043.

PMID- 25940305
TI  - Demographic factors and hospital size predict patient satisfaction variance-
      implications for hospital value-based purchasing.
AB  - BACKGROUND: Hospital Value-Based Purchasing (HVBP) incentivizes quality
      performance-based healthcare by linking payments directly to patient satisfaction
      scores obtained from Hospital Consumer Assessment of Healthcare Providers and
      Systems (HCAHPS) surveys. Lower HCAHPS scores appear to cluster in heterogeneous
      population-dense areas and could bias Centers for Medicare & Medicaid Services
      (CMS) reimbursement. OBJECTIVE: Assess nonrandom variation in patient
      satisfaction as determined by HCAHPS. DESIGN: Multivariate regression modeling
      was performed for individual dimensions of HCAHPS and aggregate scores.
      Standardized partial regression coefficients assessed strengths of predictors.
      Weighted Individual (hospital) Patient Satisfaction Adjusted Score (WIPSAS)
      utilized 4 highly predictive variables, and hospitals were reranked accordingly.
      SETTING: A total of 3907 HVBP-participating hospitals. PATIENTS: There were
      934,800 patient surveys by the most conservative estimate. MEASUREMENTS: A total
      of 3144 county demographics (US Census) and HCAHPS surveys. RESULTS: Hospital
      size and primary language (non-English speaking) most strongly predicted
      unfavorable HCAHPS scores, whereas education and white ethnicity most strongly
      predicted favorable HCAHPS scores. The average adjusted patient satisfaction
      scores calculated by WIPSAS approximated the national average of HCAHPS scores.
      However, WIPSAS changed hospital rankings by variable amounts depending on the
      strength of the predictive variables in the hospitals' locations. Structural and
      demographic characteristics that predict lower scores were accounted for by
      WIPSAS that also improved rankings of many safety-net hospitals and academic
      medical centers in diverse areas. CONCLUSIONS: Demographic and structural factors
      (eg, hospital beds) predict patient satisfaction scores even after CMS
      adjustments. CMS should consider WIPSAS or a similar adjustment to account for
      the severity of patient satisfaction inequities that hospitals could strive to
      correct.

PMID- 25940306
TI  - Salicylate activates AMPK and synergizes with metformin to reduce the survival of
      prostate and lung cancer cells ex vivo through inhibition of de novo lipogenesis.
AB  - Aspirin, the pro-drug of salicylate, is associated with reduced incidence of
      death from cancers of the colon, lung and prostate and is commonly prescribed in
      combination with metformin in individuals with type 2 diabetes. Salicylate
      activates the AMP-activated protein kinase (AMPK) by binding at the A-769662 drug
      binding site on the AMPK beta1-subunit, a mechanism that is distinct from
      metformin which disrupts the adenylate charge of the cell. A hallmark of many
      cancers is high rates of fatty acid synthesis and AMPK inhibits this pathway
      through phosphorylation of acetyl-CoA carboxylase (ACC). It is currently unknown
      whether targeting the AMPK-ACC-lipogenic pathway using salicylate and/or
      metformin may be effective for inhibiting cancer cell survival. Salicylate
      suppresses clonogenic survival of prostate and lung cancer cells at therapeutic
      concentrations achievable following the ingestion of aspirin (<1.0 mM); effects
      not observed in prostate (PNT1A) and lung (MRC-5) epithelial cell lines.
      Salicylate concentrations of 1 mM increased the phosphorylation of ACC and
      suppressed de novo lipogenesis and these effects were enhanced with the addition
      of clinical concentrations of metformin (100 MUM) and eliminated in mouse
      embryonic fibroblasts (MEFs) deficient in AMPK beta1. Supplementation of media
      with fatty acids and/or cholesterol reverses the suppressive effects of
      salicylate and metformin on cell survival indicating the inhibition of de novo
      lipogenesis is probably important. Pre-clinical studies evaluating the use of
      salicylate based drugs alone and in combination with metformin to inhibit de novo
      lipogenesis and the survival of prostate and lung cancers are warranted. 

PMID- 25940307
TI  - Functional outcomes of operative fixation of clavicle fractures in patients with
      floating shoulder girdle injuries.
AB  - BACKGROUND: Double disruptions of the superior suspensory shoulder complex,
      commonly referred to as 'floating shoulder' injuries, are ipsilateral midshaft
      clavicular and scapular neck/body fractures with a loss of bony attachment of the
      glenoid. The treatment of 'floating shoulder' injuries has been debated
      controversially for many years. The purpose of this study was to demonstrate the
      clinical and functional outcomes of patients with 'floating shoulder' injuries
      who underwent operative fixation of the clavicle fracture only. MATERIALS AND
      METHODS: Between 2002 and 2010, 32 consecutive floating shoulder injuries were
      identified in skeletally mature patients at a level I trauma center and followed
      in a single private practice. Thirteen patients met the inclusion and exclusion
      criteria for this retrospective study with a minimum 12-month follow-up. Clavicle
      and scapular fractures were identified by Current Procedural Technology codes and
      classified based on Orthopaedic Trauma Association/Arbeitsgemeinschaft fur
      Osteosynthesefragen criteria. 'Floating shoulder' injuries were surgically
      managed with only clavicular reduction and fixation utilizing modern plating
      techniques. Nonunion, malunion, implant removal, range of motion, need for
      secondary surgery, pain according to the visual analog scale (VAS), and return to
      work were measured. RESULTS: All injuries were the result of high-energy
      mechanisms. Fracture union of the clavicle was seen after initial surgical
      fixation in the majority of patients (12; 92.3 %). Final pain was reported as
      minimal (11 cases; 1-3 VAS), moderate (1 case; 4-6 VAS), and high (1 case; 7-10
      VAS) at last follow-up. Excellent range of motion (180 degrees  forward flexion
      and abduction) was observed in the majority of patients (8; 61.5 %). The
      Herscovici score was 12.9 (range 10-15) at 3 months. Unplanned surgeries included
      two clavicular implant removals and one nonunion revision. None of the patients
      required reconstruction for scapula malunion after nonoperative management.
      Twelve patients returned to previous work without restrictions. CONCLUSIONS:
      'Floating shoulder' injuries with only clavicular fixation return to function
      despite persistent scapular deformity and some residual pain. LEVEL OF EVIDENCE:
      Level IV.

PMID- 25940309
TI  - Endogenous endophthalmitis complicating Streptococcus equi subspecies
      zooepidemicus meningitis: a case report.
AB  - BACKGROUND: Streptococcus equi subspecies zooepidemicus (Streptococcus
      zooepidemicus) is a rare cause of meningitis in humans. Humans mainly get
      infected by contact with an animal source or by ingestion of unpasteurized dairy
      products. In rare cases, bacterial meningitis can be complicated by endogenous
      endophthalmitis which is frequently associated with a poor visual prognosis. CASE
      PRESENTATION: A 73 year old male Caucasian patient presented with clinical signs
      indicative of bacterial meningitis. Blood and cerebrospinal fluid cultures
      yielded beta-hemolytic, catalase-negative cocci. The strain was identified as
      Streptococcus zooepidemicus. The patient was likely infected by contact with a
      sick horse. Under antibiotic treatment, his general condition improved rapidly.
      Early after hospital admission, however, he began seeing a black spot in his left
      eye's central visual field. An ophthalmological examination revealed signs of
      endogenous endophthalmitis and so the patient underwent vitrectomy. Despite
      treatment, the visual acuity of his left eye remained severely impaired. He
      showed no further neurological deficits at hospital discharge. CONCLUSION:
      Meningitis caused by Streptococcus zooepidemicus is rare with only 27 previously
      published adult cases in the literature. Of note, this report constitutes the
      third description of endogenous endophthalmitis associated with Streptococcus
      zooepidemicus meningitis. Thus, endogenous endophthalmitis may represent a
      comparatively common complication of meningitis caused by this microorganism.

PMID- 25940308
TI  - What comes first? Multitissue involvement leading to radiographic osteoarthritis:
      magnetic resonance imaging-based trajectory analysis over four years in the
      osteoarthritis initiative.
AB  - OBJECTIVE: To assess whether the presence of structural osteoarthritis (OA)
      features over as many as 4 years prior to incident radiographic OA increases the
      risk of radiographic OA in a nested, case-control design. METHODS: We studied 355
      knees from the Osteoarthritis Initiative cohort that developed radiographic OA
      before the 48-month visit. They were matched one-to-one by sex, age, and
      contralateral knee radiographic status with a control knee. Magnetic resonance
      images (MRIs) were read for bone marrow lesions (BMLs), cartilage damage,
      meniscal damage (including tears and extrusion), Hoffa synovitis, and effusion
      synovitis. Conditional logistic regression was applied to assess the risk of
      radiographic OA with regard to the presence of BMLs (score >=2), cartilage
      lesions (score >=1.1), meniscal damage (any) and extrusion of >=3 mm +/- (score
      >=2), and Hoffa and effusion synovitis (any). Time points were defined as
      incident radiographic OA visit (P0), 1 year prior to the detection of
      radiographic OA (P -1), 2 years prior to the detection of radiographic OA (P -2),
      etc. RESULTS: The presence of Hoffa synovitis (hazard ratio [HR] 1.76 [95%
      confidence interval (95% CI) 1.18-2.64]), effusion synovitis (HR 1.81 [95% CI
      1.18-2.78]), and medial meniscal damage (HR 1.83 [95% CI 1.17-2.89]) at P -2
      predicted radiographic OA incidence. At P -1, all features but meniscal extrusion
      predicted radiographic OA, with highest odds for medial BMLs (HR 6.50 [95% CI
      2.27-18.62]) and effusion synovitis (HR 2.50 [95% CI 1.76-3.54]). The findings at
      P -3 and P -4 did not reach statistical significance. CONCLUSION: Our findings
      indicate that the presence of specific structural features of MRI-detected joint
      damage 2 years prior to incident radiographic OA increases the risk of incident
      radiographic OA. However, 1 year prior to radiographic OA, the presence of almost
      any abnormal morphologic feature increases the risk of radiographic OA in the
      subsequent year.

PMID- 25940310
TI  - Finding privacy from a public death: a qualitative exploration of how a dedicated
      space for end-of-life care in an acute hospital impacts on dying patients and
      their families.
AB  - AIMS AND OBJECTIVES: To explore the experiences and perceptions of hospital staff
      caring for dying patients in a dedicated patient/family room (named Lotus Room).
      BACKGROUND: Dying in hospital is a common outcome for people across the world.
      However, noise and activity in acute environments present barriers to quality end
      of-life care. This is of concern because care provided to dying patients has been
      shown to affect both the patients and the bereaved families. DESIGN: A
      qualitative descriptive approach was used. METHODS: Semi-structured interviews
      were conducted with 17 multidisciplinary staff and seven families provided
      information through an investigator-developed instrument. RESULTS: Qualitative
      data analysis generated three categories describing: Dying in an hospital; The
      Lotus Room; and the Outcomes for patients and families. The Lotus Room was seen
      as a large, private and, ultimately, safe space for patients and families within
      the public hospital environment. Family feedback supported staff perspectives
      that the Lotus Room facilitated family presence and communication. CONCLUSIONS:
      The privacy afforded by the Lotus Room within this acute hospital provided
      benefits for the dying patients and grieving families. Improved outcomes included
      a peaceful death for patients, which may have assisted the family with their
      bereavement. RELEVANCE TO CLINICAL PRACTICE: This study provides evidence of how
      the physical environment can address well-established barriers to quality end-of
      life care in acute hospitals.

PMID- 25940315
TI  - On the Origin of the Improvement of Electrodeposited MnOx Films in Water
      Oxidation Catalysis Induced by Heat Treatment.
AB  - Manganese oxides (MnOx ) are considered to be promising catalysts for water
      oxidation. Building on our previous studies showing that the catalytic activity
      of MnOx films electrodeposited from aqueous electrolytes is improved by a simple
      heat treatment, we have explored the origin of the catalytic enhancement at an
      electronic level by X-ray absorption spectroscopy (XAS). The Mn L-edge XA spectra
      measured at various heating stages were fitted by linear combinations of the
      spectra of the well-defined manganese oxides-MnO, Mn3 O4 , Mn2 O3 , MnO2 and
      birnessite. This analysis identified two major manganese oxides, Mn3 O4 and
      birnessite, that constitute 97 % of the MnOx films. Moreover, the catalytic
      improvement on heat treatment at 90  degrees C is related to the conversion of a
      small amount of birnessite to the Mn3 O4 phase, accompanied by an irreversible
      dehydration process. Further dehydration at higher temperature (120  degrees C),
      however, leads to a poorer catalytic performance. 

PMID- 25940316
TI  - Retargeting pre-existing human antibodies to a bacterial pathogen with an alpha
      Gal conjugated aptamer.
AB  - The ever-increasing threat of multi-drug resistant bacterial infections has
      spurred renewed interest in alternative approaches to classical antibiotic
      therapy. In contrast to other mammals, humans do not express the galactose-alpha
      1,3-galactosyl-beta-1,4-N-acetyl-glucosamine (alpha-Gal) epitope. As a result of
      exposure of humans to alpha-Gal in the environment, a large proportion of
      circulating antibodies are specific for the trisaccharide. In this study, we
      examine whether these anti-Gal antibodies can be recruited and redirected to
      exert anti-bacterial activity. We show that a specific DNA aptamer conjugated to
      an alpha-Gal epitope at its 5' end, herein termed an alphamer, can bind to group
      A Streptococcus (GAS) bacteria by recognition of a conserved region of the
      surface-anchored M protein. The anti-GAS alphamer was shown to recruit anti-Gal
      antibodies to the streptococcal surface in an alpha-Gal-specific manner, elicit
      uptake and killing of the bacteria by human phagocytes, and slow growth of
      invasive GAS in human whole blood. These studies provide a first in vitro proof
      of concept that alphamers have the potential to redirect pre-existing antibodies
      to bacteria in a specific manner and trigger an immediate antibacterial immune
      response. Further validation of this novel therapeutic approach of applying alpha
      Gal technology in in vivo models of bacterial infection is warranted. KEY
      MESSAGES: . alpha-Gal-tagged aptamers lead to GAS opsonization with anti-Gal
      antibodies. . alpha-Gal-tagged aptamers confer phagocytosis and killing of GAS
      cells by human phagocytes. . alpha-Gal-tagged aptamers reduces replication of GAS
      in human blood. . alpha-Gal-tagged aptamers may have the potential to be used as
      novel passive immunization drugs.

PMID- 25940318
TI  - Identification of ionic liquid components by RP-HPLC with diode array detector
      using chaotropic effect and perturbation technique.
AB  - Sodium hexafluorophosphate, perchlorate and tetrafluoroborate were applied as the
      ion-pair reagents in reversed-phase chromatography of several imidazolium-based
      ionic liquids. The optimization of the retention was performed by changing the
      kind of organic modifier (methanol, acetonitrile), concentration and the kind of
      the ion-pair reagents in the mobile phase and the column kind (Zorbax SB-C18,
      Zorbax SB-Phenyl, Zorbax SB-CN, Zorbax SB-NH2 and Supelcosil LC-F). The
      selectivity of the proposed chromatographic systems according to the cation kind
      was compared on the basis of the resolution of ionic liquid mixture. The
      perturbation method was applied to identify the anion kind. The formation of ion
      associated complexes between promethazine as counter-cation and chaotropic anions
      controlling their retention was confirmed. 

PMID- 25940317
TI  - DcR3 suppresses influenza virus-induced macrophage activation and attenuates
      pulmonary inflammation and lethality.
AB  - Influenza A virus (IAV) infects macrophages and stimulates innate immunity
      receptors and sensors to produce proinflammatory cytokines and chemokines, which
      are responsible for IAV-induced pulmonary inflammation and injury. Decoy receptor
      3 (DcR3) is a soluble protein belonging to the tumor necrosis factor receptor
      superfamily (TNFRSF), and is able to skew macrophage differentiation into an M2
      phenotype. We demonstrated that DcR3 attenuated IAV-induced secretion of
      proinflammatory cytokines and chemokine from macrophages, and mitigated pulmonary
      infiltration and reduce lethality. Proteome-wide phosphoproteomic mapping
      revealed that DcR3 not only activated STK10, a negative regulator of cell
      migration, but also inactivated PKC-alpha, which are crucial for the activation
      of ERK and JNK in human macrophages. Furthermore, less pulmonary infiltration
      with lower levels of proinflammatory cytokines and chemokine in bronchoalveolar
      lavage fluid (BALF) were observed in DcR3-transgenic mice. Moreover, recombinant
      DcR3.Fc and heparan sulfate proteoglycan binding domain of DcR3.Fc (HBD.Fc)
      fusion proteins attenuated weight loss and protected mice from IAV-induced
      lethality. Thus, DcR3-mediated protection is not only via suppression of
      proinflammatory cytokine and chemokine release, but also via activation of STK10
      to inhibit cell infiltration. DcR3 fusion proteins may become therapeutic agents
      to protect host from IAV-induced lethality in the future. KEY MESSAGE: * DcR3
      suppresses IAV-induced cytokine secretion.* DcR3 inhibits IAV-induced JNK and ERK
      activation in human macrophages.* DcR3 downregulates TLR3 and 7 expressions in
      human macrophages.* DcR3 protects mice from IAV-induced lethality.

PMID- 25940319
TI  - Retraction Note to: Nafamostat mesilate inhibits the expression of HMGB1 in
      lipopolysaccharide-induced acute lung injury.

PMID- 25940320
TI  - The use of a needle guide kit improves the stability of ultrasound-guided
      techniques.
AB  - A needle guide kit will be able to improve visibility on ultrasonic images. We
      examined the degree of stability using a SIVA guide. The SIVA guide is a needle
      guide kit in which the angle is not restricted, allowing the puncture to be made
      at any angle. We punctured the Blue PhantomTM with a high-frequency linear probe
      with a SIVA guide and measured the intensities of the needle at depths of 0.5,
      1.0, 1.5, and 2.0 cm on the ultrasound image with Image J software. We set all
      punctures angles at 45 degrees from the Blue PhantomTM. Six anesthesiologists
      with >7 years experience performed two punctures-one case was punctured with a
      SIVA guide and the other was punctured without a SIVA guide. Some significant
      differences were noted in the results between the two punctures at depths of 1.0,
      1.5, and 2.0 cm. We were able to prove that the use of a needle guide kit could
      improve visibility on ultrasonic images.

PMID- 25940321
TI  - The community comes to campus: the Patient and Community Fair.
AB  - BACKGROUND: Community-based learning connects students with local communities so
      that they learn about the broad context in which health and social care is
      provided; however, students usually interact with only one or a few organisations
      that serve a particular population. One example of a community-based learning
      activity is the health fair in which students provide health promotion and
      screening for local communities. CONTEXT: We adapted the health fair concept to
      develop a multi-professional educational event at which, instead of providing
      service, students learn from and about the expertise and resources of not-for
      profit organisations. INNOVATION: The fair is an annual 1-day event that students
      can attend between, or in place of, classes. Each community organisation has a
      booth to display information. One-hour 'patient panels' are held on a variety of
      topics throughout the day. Evaluation methods include questionnaires, exit
      interviews and visitor tracking sheets. Over 5 years (2009-2013), the fair
      increased in size with respect to estimated attendance, number of participating
      organisations, number of patient panels and number of students for whom the fair
      is a required curriculum component. Students learn about a range of patient
      experiences and community resources, and information about specific diseases or
      conditions. IMPLICATIONS: The fair is an efficient way for students to learn
      about a range of community organisations. It fosters university-community
      engagement through continuing connections between students, faculty members and
      community organisations. Lessons learned include the need for community
      organisations to have techniques to engage students, and ways to overcome
      challenges of evaluating an informal 'drop-in' event. The fair is an efficient
      way for students to learn about a range of community organisations.

PMID- 25940322
TI  - Structural and Gel Textural Properties of Soy Protein Isolate When Subjected to
      Extreme Acid pH-Shifting and Mild Heating Processes.
AB  - Changes in the structural and gel textural properties were investigated in soy
      protein isolate (SPI) that was subjected to extreme acid pH-shifting and mild
      heating processes. The SPI was incubated up to 5 h in pH 1.5 solutions at room
      temperature or in a heated water bath (50 or 60  degrees C) to lead to protein
      structural unfolding, followed by refolding at pH 7.0 for 1 h. The combination of
      pH-shifting and heating treatments resulted in drastic increases in the SPI gel
      penetration force (p < 0.05). These treatments also significantly enforced the
      conversion of sulphydryl groups into disulfides, increased the particle size and
      hydrophobicity values, reduced the protein solubility (p < 0.05), and
      strengthened the disulfide-mediated aggregation of SPI. The intrinsic
      fluorescence spectroscopy results indicated structural unravelling when protein
      was subjected to acidic pH-shifting in combination with heating processes. The
      slight loss of secondary structure was observed by circular dichroism. These
      results suggested that pH-shifting combined with heating treatments provide great
      potential for the production of functionality-improved SPI, with the improved
      gelling property highly related to changes in the protein structure and
      hydrophobic aggregation. 

PMID- 25940323
TI  - Increased pancreas cancer in a bio-technological research laboratory.
AB  - BACKGROUND: Pancreatic cancer is extremely rare among people under 55 years old.
      Its prognosis is poor, and the causal background remains almost unresolved. A
      previous study observed an increased occurrence of pancreatic cancer in workers
      in a French biochemical laboratory. METHODS:  CASE REPORT: During an approximate
      10 year period in a Danish bio-chemical laboratory with about 50 stable
      employees, four cases of pancreatic cancer have been diagnosed at a mean age of
      53 years. Approximately 0.02 cases should be expected if the laboratory employees
      had experienced the same rate of pancreatic cancer as that observed in the
      respective general Danish populations. RESULT: All the four cases had a long-term
      occupational history of exposure to carcinogens during the early bio-technology
      period. CONCLUSIONS: Causal conclusions cannot be made yet, but observation of
      former and present workers in biotechnological laboratories and their cancer
      occurrence is warranted.

PMID- 25940324
TI  - Clinically isolated syndrome--Rethinking the diagnosis.
AB  - A diagnostic lacuna in clinically isolated syndrome (CIS) is the prognostic
      uncertainty of approximately 20% of patients who do not meet the radiological
      criteria based on magnetic resonance imaging (MRI) of the brain. A study by
      Tintore et al. noted that 23% of patients who had normal MRI findings but had
      oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) developed clinically
      definite multiple sclerosis (CDMS), compared with 4% who had normal MRI findings
      but no OCBs in CSF (Tintore et al. 2008). Since a diagnosis of CIS cannot be made
      if MRI data are equivocal, the opportunity for early treatment is lost if non
      radiological data are not taken into diagnostic consideration. In this article, a
      case for inclusion of cerebrospinal fluid data in the diagnosis of CIS is made,
      and a distinction is drawn in certain patient cohorts based on ethnicity, that
      demands urgent research. Certain ethnic cohorts such as African Americans (AAs)
      may have a higher risk of delayed diagnosis if CSF data are ignored. At the
      current time, the diagnosis of CIS continues to favor clinical and radiological
      evidence and this article aims to change that perspective. 

PMID- 25940325
TI  - Selective disappearance of medial back muscles in a case of myotonic dystrophy
      type 1.
AB  - Here, we report a unique case of late-onset myotonic dystrophy type 1 in a 64
      year-old woman, with selective disappearance of the medial lower back muscles. We
      compared the clinical features of this patient with those of a cohort of 29
      patients with myotonic dystrophy type 1 to clarify the correlation between
      clinical features and lower back muscle atrophy. After classification into three
      subgroups according to muscle atrophy pattern, medial muscle atrophy was present
      in 17.2% of the patients. Affected patients were older at onset than non-affected
      patients, and limb muscle power and respiratory function decreased with atrophy
      progression. 

PMID- 25940326
TI  - Comparison of bacterial community structures of terrestrial cyanobacterium Nostoc
      flagelliforme in three different regions of China using PCR-DGGE analysis.
AB  - Filamentous Nostoc flagelliforme form colloidal complex, with beaded cells
      interacting with other bacteria embedded in the complex multilayer sheath.
      However, the species of bacteria in the sheath and the interaction between N.
      flagelliforme and associated bacteria remain unclear. In this study, PCR
      denaturing gradient gel electrophoresis (DGGE) was used to investigate the
      bacterial communities of N. flagelliforme from three regions of China. DGGE
      patterns showed variations in all samples, exhibiting 25 discrete bands with
      various intensities. The diversity index analysis of bands profiles suggested the
      high similarity of bacterial communities to each other but also the dependence of
      microbial composition on each location. Phylogenetic affiliation indicated that
      the majority of the sequences obtained were affiliated with Actinobacteria,
      Cyanobacteria, Proteobacteria, Acidobacteria, Bacteroidetes, of which
      Cyanobacteria was dominant, followed the Proteobacteria. Members of the genus
      Nostoc were the most abundant in all samples. Rhizobiales and Actinobacteria were
      identified, whereas, Craurococcus, Caulobacter, Pseudomonas, Terriglobus and
      Mucilaginibacter were also identified at low levels. Through comparing the
      bacterial composition of N. flagelliforme from different regions, it was revealed
      that N. flagelliforme could facilitate the growth of other microorganisms
      including both autotrophic bacteria and heterotrophic ones and positively
      contributed to their harsh ecosystems. The results indicated N. flagelliforme
      played an important role in diversifying the microbial community composition and
      had potential application in soil desertification. 

PMID- 25940327
TI  - The influence of nickel on the bioremediation of multi-component contaminated
      tropical soil: microcosm and batch bioreactor studies.
AB  - Large petrochemical discharges are responsible for organic and inorganic
      pollutants in the environment. The purpose of this study was to evaluate the
      influence of nickel, one of the most abundant inorganic element in crude oil and
      the main component of hydrogen catalysts for oil refining, on the microbial
      community structure in artificially petroleum-contaminated microcosms and in
      solid phase bioreactor studies. In the presence of metals, the oil biodegradation
      in microcosms was significantly delayed during the first 7 days of operation.
      Also, increasing amounts of moisture generated a positive influence on the
      biodegradation processes. The oil concentration, exhibiting the most negative
      influence at the end of the treatment period. Molecular fingerprinting analyses
      (denaturing gradient gel electrophoresis--DGGE) indicated that the inclusion of
      nickel into the contaminated soil promoted direct changes to the microbial
      community structure. By the end of the experiments, the results of the total
      petroleum hydrocarbons removal in the bioreactor and the microcosm were similar,
      but reductions in the treatment times were observed with the bioreactor
      experiments. An analysis of the microbial community structure by DGGE using
      various markers showed distinct behaviors between two treatments containing high
      nickel concentrations. The main conclusion of this study was that Nickel promotes
      a significant delay in oil biodegradation, despite having only a minor effect
      over the microbial community.

PMID- 25940328
TI  - Effect of Saccharomyces cerevisiae and Candida zemplinina on quercetin, vitisin A
      and hydroxytyrosol contents in Sangiovese wines.
AB  - Quercetins, vitisin A and hydroxytyrosol are phenolic compounds possessing
      several positive properties to human health. This paper refers on the possible
      effects of two wine yeast species, Saccharomyces cerevisiae and Starmerella
      bacillaris (synonym Candida zemplinina) on the accumulation of these compounds in
      experimental Sangiovese wines. A single lot of Sangiovese grapes was fermented by
      S. cerevisiae alone or by sequential inoculum of C. zemplinina and S. cerevisiae
      under two aeration conditions. The accumulation of quercetin and its glycosides
      resulted only influenced by must aeration. However, yeast species occurring in
      the fermentative process affected the relative abundances among the different
      forms of quercetin. Vitisin A contents were higher in wines produced in the
      presence of C. zemplinina. Finally, higher concentrations of hydroxytyrosol and
      tyrosol were found in wines produced by S. cerevisiae alone under non-aerated
      condition. The fermentation of different Sangiovese grape musts carried out by
      the assayed S. cerevisiae strain pointed out that slow fermentation kinetics lead
      to higher levels of hydroxytyrosol and tyrosol. The study underlines the role of
      yeast species in determining the accumulation of bioactive compounds in
      Sangiovese wine.

PMID- 25940329
TI  - Intraoperative fluid management in children - a comparison of three fluid
      regimens.
AB  - BACKGROUND: Fluid therapy is essential for safe perioperative management.
      Numerous reports of serious complications, including brain damage and death of
      children, as a result of inappropriate fluid management, have been published. The
      aim of this study was to assess the effects of intraoperative fluids on serum
      glucose and electrolytes concentrations as well as serum osmolality. METHODS: 91
      children, ASA I and II, undergoing elective ENT surgery were enrolled to this
      prospective, randomized, open-label study. They were randomly assigned to
      receive: group G5W: 5% glucose in water solution, group GNaCl: 3.33% glucose in
      0.3% NaCl, and group RA: Ringer's acetate. Serum glucose, sodium, potassium,
      phosphate concentrations and serum osmolality were analysed before induction of
      anaesthesia, immediately after completion of surgery and 60 min later. RESULTS:
      Postoperative hyperglycaemia was observed in 94% of children in group G5W and in
      37% of group GNaCl. In all the groups glucose concentration increased
      significantly after surgery. Postoperative hyponatraemia occurred in 36% of
      patients in the group G5W, and in 3.7% in the group GNaCl. Neither hyperglycaemia
      nor hyponatremia occurred in the group RA. Postoperative osmolality decreased
      significantly in groups G5W and GNaCl and remained unchanged in the group RA.
      CONCLUSIONS: Ringer's acetate did not cause significant changes in glucose and
      electrolyte concentrations, so it seems to be the safest for intraoperative use
      in children undergoing elective surgery. Hypotonic fluids may cause
      hyperglycaemia and hyponatraemia so they should be avoided intraoperatively.

PMID- 25940330
TI  - Percutaneous cryoanalgesia in pain management: a case-series.
AB  - BACKGROUND: Cryoanalgesia, also known as cryoneuroablation or cryoneurolysis, is
      a specialized technique for providing long-term pain relief. METHODS: There are
      presented retrospective data on pain relief and changes in function after
      cryoanalgesia techniques: we describe the effect of this procedure on articular
      facet syndromes, sacroiliac pain and knee pain. We reviewed records of 18
      patients with articular lumbar facet pain, knee pain and sacroiliac pain.
      RESULTS: Both the visual analog scale and the Patient's global impression of
      change scale showed an increase in patients' satisfaction already at 1 month
      after cryoablation, with the best scores after three months. Only three
      individuals displayed a worse condition than at the first month. CONCLUSION: The
      majority of patients experienced a clinically relevant degree of pain relief and
      improved function following percutaneous cryoanalgesia.

PMID- 25940331
TI  - Balanced hydroxyethyl starch solution and hyperglycaemia in non diabetics - a
      prospective, randomized and controlled study.
AB  - BACKGROUND: There are very few studies that have examined the effect of
      hydroxyethyl starch (HES) solutions on blood glucose level. The study was aimed
      to compare the effects on blood glucose levels in patients undergoing lower limb
      surgeries under neuraxial block, receiving HES with those receiving 0.9% saline.
      PATIENTS AND METHODS: 160 non-diabetic ASA I or II patients, aged between 18-65
      years were selected for the trial. Patients were divided into two groups; Group C
      (n = 80, patients received only 0.9% saline for preloading and maintenance until
      six hours of the end of preloading) and Group T (n = 80, patients received
      TetraspanTM 10 mL kg-1, for preloading and 0.9% saline for maintenance until six
      hours from the end of preloading). Blood glucose was recorded prior to the start
      of preloading and repeated at two, four and six hours after the end of HES
      infusion or the preloading dose of 0.9% saline. RESULTS: The following blood
      glucose levels were comparable at all times; fasting/baseline (85.3 +/- 19.2 mg
      dL-1 in group C and 95.4 +/- 17.3 mg dL-1 in group T); increase in blood glucose
      concentration at 2 hours (6.44 +/- 20.59 mg dL-1 in group C and 10.8 +/- 18.1 mg
      dL-1 in group T); 4 hours (4.1 +/- 12.1 mg dL-1 in group C and 3.5 +/- 11.8 mg dL
      1 in group T); and at 6 hours (2.9 +/- 13.4 mg dL-1 in group C and 3.5 +/- 10.6
      mg dL-1 in group T). CONCLUSION: A balanced HES solution administered
      intravenously did not cause an increase in blood glucose concentrations compared
      to those who received 0.9% saline.

PMID- 25940332
TI  - Neurophysiological foundations of sleep, arousal, awareness and consciousness
      phenomena. Part 1.
AB  - The paper presents a state of the art review of the anatomical and physiological
      foundations of awareness, consciousness, arousal and sleep phenomena and provides
      current definitions. We describe 20(th) century discoveries that were milestones
      in the understanding of central nervous system function. Structures that are
      specifically involved in the quantitative and qualitative aspects of awareness
      are characterised here. We also describe the relationships between particular
      groups of neurons, their positive and negative feedback loops, and the
      neurotransmitters engaged in states of arousal and sleep.

PMID- 25940333
TI  - Neurophysiological foundations of sleep, arousal, awareness and consciousness
      phenomena. Part 2.
AB  - Second section of the paper contains description of hypothalamic centres involved
      in regulation of circadian rhythms. Connections between these neurons and
      activating reticular system are described. Transition from arousal to sleep,
      promoted by substances called somnogens, is discussed. Lastly, function of
      suprachiasmatic nucleus as circadian oscillator is presented. 

PMID- 25940334
TI  - Neurogenic stunned myocardium - do we consider this diagnosis in patients with
      acute central nervous system injury and acute heart failure?
AB  - Neurogenic stunned myocardium (NSM) is defined as myocardial injury and
      dysfunction of a sudden onset, occurring after various types of acute brain
      injury as a result of an imbalance in the autonomic nervous system. The typical
      spectrum of clinically observed abnormalities includes acute left ventricular
      failure, not uncommonly progressing to cardiogenic shock with hypotension that
      requires inotropic agents, pulmonary oedema and various arrhythmias. Commonly
      seen electrocardiographic changes include: prolonged QT interval, ST segment
      changes, T-wave inversion, a new Q-wave or U-wave. Echocardiography shows both an
      impaired both systolic and diastolic function of the left ventricle. Biochemical
      markers of NSM comprise metabolic acidosis and increased cardiac enzymes and
      markers: creatine kinase (CK), and CK-MB, troponin I and B-type natriuretic
      peptide. The main cause of NSM is myocardial injury induced by local
      catecholamine release from nerve endings within the myocardium. Recently, a
      theory has been proposed to classify NSM as one of the stress-related
      cardiomyopathies, together with Takotsubo cardiomyopathy, acute left ventricular
      failure in the critically ill, cardiomyopathy associated with pheochromacytoma
      and exogenous catecholamine administration. The occurrence of NSM increases the
      risk of life-threatening complications, death, and worsens neurologic outcome. As
      far as we know, treatment should generally focus on the underlying neurologic
      process in order to maximize neurologic recovery. Improvement in neurologic
      pathology leads to rapid improvement in cardiac function and its full recovery,
      as NSM is a fully reversible condition if the patient survives. Awareness of the
      existence of NSM and a deeper knowledge of its etiopathology may reduce
      diagnostic errors, optimise its treatment. 

PMID- 25940335
TI  - Authorisation of organ procurement - is it influential factor for the
      identification of potential organ donors?
AB  - For many years, the authorisation of organ procurement has been discussed as a
      contributory factor to the number of potential organ donors. This paper presents
      different forms of authorisation and their influence on the decisions of both
      individuals and society. The general legal framework for the authorisation of
      organ procurement in Poland is described along with the solutions implemented by
      countries in which both implicit and explicit consent models are in effect. The
      presented arguments suggest that the form of authorisation does not directly
      influence the number of organs procured for transplantation. 

PMID- 25940336
TI  - Does Residency Selection Criteria Predict Performance in Orthopaedic Surgery
      Residency?
AB  - BACKGROUND: More than 1000 candidates applied for orthopaedic residency positions
      in 2014, and the competition is intense; approximately one-third of the
      candidates failed to secure a position in the match. However, the criteria used
      in the selection process often are subjective and studies have differed in terms
      of which criteria predict either objective measures or subjective ratings of
      resident performance by faculty. QUESTIONS/PURPOSES: Do preresidency selection
      factors serve as predictors of success in residency? Specifically, we asked which
      preresidency selection factors are associated or correlated with (1) objective
      measures of resident knowledge and performance; and (2) subjective ratings by
      faculty. METHODS: Charts of 60 orthopaedic residents from our institution were
      reviewed. Preresidency selection criteria examined included United States Medical
      Licensing Examination (USMLE) Step 1 and Step 2 scores, Medical College Admission
      Test (MCAT) scores, number of clinical clerkship honors, number of letters of
      recommendation, number of away rotations, Alpha Omega Alpha (AOA) honor medical
      society membership, fourth-year subinternship at our institution, and number of
      publications. Resident performance was assessed using objective measures
      including American Board of Orthopaedic Surgery (ABOS) Part I scores and
      Orthopaedics In-Training Exam (OITE) scores and subjective ratings by faculty
      including global evaluation scores and faculty rankings of residents. We tested
      associations between preresidency criteria and the subsequent objective and
      subjective metrics using linear correlation analysis and Mann-Whitney tests when
      appropriate. RESULTS: Objective measures of resident performance namely, ABOS
      Part I scores, had a moderate linear correlation with the USMLE Step 2 scores (r
      = 0.55, p < 0.001) and number of clinical honors received in medical school (r =
      0.45, p < 0.001). OITE scores had a weak linear correlation with the number of
      clinical honors (r = 0.35, p = 0.009) and USMLE Step 2 scores (r = 0.29, p =
      0.02). With regards to subjective outcomes, AOA membership was associated with
      higher scores on the global evaluation (p = 0.005). AOA membership also
      correlated with higher global evaluation scores (r = 0.60, p = 0.005) with the
      strongest correlation existing between AOA membership and the "interpersonal and
      communication skills" subsection of the global evaluations. CONCLUSIONS: We found
      that USMLE Step 2, number of honors in medical school clerkships, and AOA
      membership demonstrated the strongest correlations with resident performance. Our
      goal in analyzing these data was to provide residency programs at large a sense
      of which criteria may be "high yield" in ranking applicants by analyzing data
      from within our own pool of residents. Similar studies across a broader scope of
      programs are warranted to confirm applicability of our findings. The continually
      emerging complexities of the field of orthopaedic surgery lend increasing
      importance to future work on the appropriate selection and training of
      orthopaedic residents.

PMID- 25940337
TI  - Does Integrated Fixation Provide Benefit in the Reconstruction of Posttraumatic
      Tibial Bone Defects?
AB  - BACKGROUND: Limb salvage in the presence of posttraumatic tibial bone loss can be
      accomplished using the traditional Ilizarov method of distraction osteogenesis
      with circular external fixation. Internal fixation placed at the beginning of the
      consolidation phase, so-called integrated fixation, may allow for earlier removal
      of the external fixator but introduces concerns about cross-contamination from
      the additional open procedure and maintenance of bone regenerate stability.
      QUESTIONS/PURPOSES: Among patients deemed eligible for integrated fixation, we
      sought to determine: (1) Does integrated fixation decrease the time in the
      external fixator? (2) Is there a difference in the rate of complications between
      the two groups? (3) Are there differences in functional and radiographic results
      between integrated fixation and the traditional Ilizarov approach of external
      fixation alone? METHODS: Between January 2006 and December 2012, we treated 58
      patients (58 tibiae) with posttraumatic tibial bone loss using the Ilizarov
      method. Of those, 30 patients (52%) were treated with the "classic technique"
      (external fixator alone) and 28 (48%) were treated with the "integrated
      technique" (a combination of an external fixator and plating or insertion of an
      intramedullary nail). During that period, the general indications for use of the
      integrated technique were closed physes, no active infection, and a healed soft
      tissue envelope located at the intended internal fixation site; the remainder of
      the patients were treated with the classic technique. Followup on 30 (100%) and
      28 (100%) patients in the classic and integrated techniques, respectively, was
      achieved at a minimum of 1 year (mean, 3 years; range, 1-8 years). Adverse events
      were reported as problems, obstacles, and complications according to the
      publication by Paley. Problems and obstacles are managed by nonoperative and
      operative means, respectively; in addition, they resolve completely with
      treatment. Complications, according to the Paley classification, result in
      permanent sequelae. Functional and radiographic results were reported using the
      Association for the Study and Application of Methods of Ilizarov scoring system.
      RESULTS: Overall, there was a mean of four (range, 2-5) surgical procedures to
      complete the tibial reconstruction with a similar incidence of unplanned surgical
      procedures (obstacles) between the two groups (p = 0.87). Patients treated with
      integrated fixation spent less time in the external fixator, 7 months (range, 5
      20 months) versus 11 months (range, 1-15 months; p < 0.001). There were seven
      problems, 15 obstacles, and zero complications in the classic group. Ten
      problems, 15 obstacles, and one complication occurred in the integrated fixation
      group. There was no difference in the severity (p = 0.87) or number (p = 0.40) of
      complications between both groups. Good to excellent Association for the Study
      and Application of Methods of Ilizarov function and bone scores were obtained in
      100% and 98% of patients, respectively. CONCLUSIONS: The integrated fixation
      method allows for a more efficient limb salvage surgical reconstruction in
      patients carefully selected for that approach, whereas the frequency of adverse
      events and ability to restore limb lengths was not different between the groups
      with the numbers available. Careful placement of external fixation pins is
      critical to decrease cross-contamination with planned internal fixation
      constructs. In this study of posttraumatic tibial bone defect reconstruction,
      good/excellent results were found in all patients after a mean of four surgical
      procedures; however, a larger multicenter prospective study would allow for more
      robust and generalizable conclusions. LEVEL OF EVIDENCE: Level III, therapeutic
      study.

PMID- 25940339
TI  - Standardizing Immunohistochemistry: A New Reference Control for Detecting
      Staining Problems.
AB  - A new standardized immunohistochemistry (IHC) control for breast cancer testing
      comprises formalin-fixed human epidermal growth factor receptor 2, estrogen
      receptor, or progesterone receptor peptide antigens covalently attached to 8-um
      glass beads. The antigen-coated beads are suspended in a liquid matrix that
      hardens upon pipetting onto a glass microscope slide. The antigen-coated beads
      remain in place through deparaffinization, antigen retrieval, and immunostaining.
      The intensity of the beads' stain provides feedback regarding the efficacy of
      both antigen retrieval and immunostaining. As a first report, we tested the
      sensitivity and specificity of the new IHC controls ("IHControls"). To evaluate
      sensitivity, various staining problems were simulated. IHControls detected
      primary and secondary reagent degradation similarly to tissue controls. This
      first group of IHControls behaved similarly to tissue controls expressing high
      concentrations of the antigen. The IHControls were also able to detect
      aberrations in antigen retrieval, as simulated by sub-optimal times or
      temperatures. Specificity testing revealed that each antigen-coated bead was
      specific for its cognate IHC test antibody. The data support the conclusion that,
      like tissue controls, IHControls are capable of verifying the analytic components
      of an immunohistochemical stain. Unlike tissue controls, IHControls are prepared
      in large bulk lots, fostering day-to-day reproducibility that can be standardized
      across laboratories.

PMID- 25940340
TI  - Pain, hyperalgesia and stress.

PMID- 25940341
TI  - Do observers use the same facial movements that encode pain when inferring pain
      in others?

PMID- 25940338
TI  - Using Pharmacokinetic Profiles and Digital Quantification of Stained Tissue
      Microarrays as a Medium-Throughput, Quantitative Method for Measuring the
      Kinetics of Early Signaling Changes Following Integrin-Linked Kinase Inhibition
      in an In Vivo Model of Cancer.
AB  - A small molecule inhibitor (QLT0267) targeting integrin-linked kinase is able to
      slow breast tumor growth in vivo; however, the mechanism of action remains
      unknown. Understanding how targeting molecules involved in intersecting signaling
      pathways impact disease is challenging. To facilitate this understanding, we used
      tumor tissue microarrays (TMA) and digital image analysis for quantification of
      immunohistochemistry (IHC) in order to investigate how QLT0267 affects signaling
      pathways in an orthotopic model of breast cancer over time. Female NCR nude mice
      were inoculated with luciferase-positive human breast tumor cells (LCC6(Luc)) and
      tumor growth was assessed by bioluminescent imaging (BLI). The plasma levels of
      QLT0267 were determined by LC-MS/MS methods following oral dosing of QLT0267 (200
      mg/kg). A TMA was constructed using tumor tissue collected at 2, 4, 6, 24, 78 and
      168 hr after treatment. IHC methods were used to assess changes in ILK-related
      signaling. The TMA was digitized, and Aperio ScanScope and ImageScope software
      were used to provide semi-quantitative assessments of staining levels. Using
      medium-throughput IHC quantitation, we show that ILK targeting by QLT0267 in vivo
      influences tumor physiology through transient changes in pathways involving AKT,
      GSK-3 and TWIST accompanied by the translocation of the pro-apoptotic protein BAD
      and an increase in Caspase-3 activity.

PMID- 25940342
TI  - Predictors of physical activity at 12 month follow-up after a supervised exercise
      intervention in postmenopausal women.
AB  - BACKGROUND: Few studies have examined recreational physical activity (RPA) after
      participating in a structured exercise intervention. More specifically, little is
      known about the long-term effects of exercise interventions in post-menopausal
      women. This study had two objectives: 1) To compare RPA in postmenopausal women
      in the exercise group and the control group 12 months after the end of the
      Alberta Physical Activity and Breast Cancer Prevention (ALPHA) Trial; and 2) To
      apply the Theory of Planned Behaviour (TPB) to identify predictors of RPA 12
      months post-intervention among women in the exercise group. METHODS: Self
      reported RPA 12-months post-intervention from a validated questionnaire was used
      to estimate RPA levels for control group (118/160, 74% response) and exercise
      group participants (126/160, 79% response). Bivariate analysis was used to
      compare RPA between exercise and control group participants and to identify TPB
      variables for multivariate analysis. Logistic regression was applied to TPB data
      collected from self- administered questionnaires at end of trial by exercise
      group participants (126/160, 79% response) to identify predictors of long-term
      RPA. RESULTS: At 12 months post-intervention, 62% of women in the exercise group
      were active compared to 58% of controls (p = 0.52). Of the TPB constructs
      examined, self-efficacy (OR =2.98 (1.08-8.20)) and behavioural beliefs (OR = 1.46
      (1.03-2.06)) were identified as predictors of RPA for exercise group
      participants. CONCLUSIONS: Levels of RPA in the exercise and control groups were
      comparable 12 months post intervention, indicating that participation in the
      ALPHA trial was associated with increased physical activity in previously
      inactive women, regardless of randomization into either the exercise group or in
      the control group. Exercise interventions that promote self-efficacy and positive
      behavioural beliefs have the potential to have long-term impacts on physical
      activity behaviour, although further research is needed to examine additional
      psychological, social and environmental predictors of long-term RPA in post
      menopausal women. TRIAL REGISTRATION: ClinicalTrials.gov NCT00522262.

PMID- 25940343
TI  - Incidence of and mortality from kidney disease in over 600,000 insured Swedish
      dogs.
AB  - Kidney disease is an important cause of morbidity and mortality in dogs.
      Knowledge about the epidemiology of kidney disease in the dog population is
      valuable and large-scale epidemiological studies are needed. The aim of the
      present study was to use insurance data to estimate kidney-related morbidity and
      mortality in the Swedish dog population. Insurance company data from insured dogs
      during the years 1995-2006 were studied retrospectively. Incidence and mortality
      were calculated for the whole group of dogs as well as divided by sex and breed.
      The total number of veterinary care insured dogs was 665,245. The total incidence
      of kidney disease in this group of dogs was 15.8 (15.3-16.2) cases/10,000 dog
      years at risk. The number of dogs in the life insurance was 548,346 and in this
      group the total kidney-related mortality was 9.7 (9.3-10.2) deaths/10,000 dog
      years at risk. The three breeds with the highest incidence of kidney disease were
      the Bernese mountain dog, miniature schnauzer and boxer. The three breeds with
      the highest mortality caused by kidney disease were the Bernese mountain dog,
      Shetland sheepdog and flat-coated retriever. In conclusion, the epidemiological
      information provided in this study concerning kidney disease in dogs can provide
      valuable information for future research. 

PMID- 25940344
TI  - Reversible water uptake/release by thermoresponsive polyelectrolyte hydrogels
      derived from ionic liquids.
AB  - Thermoresponsive polyelectrolyte hydrogels, derived from tetra-n-alkylphosphonium
      3-sulfopropyl methacrylate-type ionic liquid monomers, show reversible water
      uptake/release, in which the gels absorb/desorb water for at least ten cycles via
      a lower critical solution temperature-type phase transition. 

PMID- 25940345
TI  - Hsp72 is targeted to the mitotic spindle by Nek6 to promote K-fiber assembly and
      mitotic progression.
AB  - Hsp70 proteins represent a family of chaperones that regulate cellular
      homeostasis and are required for cancer cell survival. However, their function
      and regulation in mitosis remain unknown. In this paper, we show that the major
      inducible cytoplasmic Hsp70 isoform, Hsp72, is required for assembly of a robust
      bipolar spindle capable of efficient chromosome congression. Mechanistically,
      Hsp72 associates with the K-fiber-stabilizing proteins, ch-TOG and TACC3, and
      promotes their interaction with each other and recruitment to spindle
      microtubules (MTs). Targeting of Hsp72 to the mitotic spindle is dependent on
      phosphorylation at Thr-66 within its nucleotide-binding domain by the Nek6
      kinase. Phosphorylated Hsp72 concentrates on spindle poles and sites of MT
      kinetochore attachment. A phosphomimetic Hsp72 mutant rescued defects in K-fiber
      assembly, ch-TOG/TACC3 recruitment and mitotic progression that also resulted
      from Nek6 depletion. We therefore propose that Nek6 facilitates association of
      Hsp72 with the mitotic spindle, where it promotes stable K-fiber assembly through
      recruitment of the ch-TOG-TACC3 complex.

PMID- 25940346
TI  - Head-to-tail regulation is critical for the in vivo function of myosin V.
AB  - Cell organization requires regulated cargo transport along cytoskeletal elements.
      Myosin V motors are among the most conserved organelle motors and have been well
      characterized in both yeast and mammalian systems. Biochemical data for mammalian
      myosin V suggest that a head-to-tail autoinhibitory interaction is a primary
      means of regulation, but the in vivo significance of this interaction has not
      been studied. Here we generated and characterized mutations in the yeast myosin V
      Myo2p to reveal that it is regulated by a head-to-tail interaction and that loss
      of regulation renders the myosin V constitutively active. We show that an
      unregulated motor is very deleterious for growth, resulting in severe defects in
      Myo2-mediated transport processes, including secretory vesicle transport,
      mitochondrial inheritance, and nuclear orientation. All of the defects associated
      with motor misregulation could be rescued by artificially restoring regulation.
      Thus, spatial and temporal regulation of myosin V in vivo by a head-to-tail
      interaction is critical for the normal delivery functions of the motor.

PMID- 25940349
TI  - C. elegans Anillin proteins regulate intercellular bridge stability and germline
      syncytial organization.

PMID- 25940347
TI  - Rab27a controls HIV-1 assembly by regulating plasma membrane levels of
      phosphatidylinositol 4,5-bisphosphate.
AB  - During the late stages of the HIV-1 replication cycle, the viral polyprotein
      Pr55(Gag) is recruited to the plasma membrane (PM), where it binds
      phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and directs HIV-1 assembly. We
      show that Rab27a controls the trafficking of late endosomes carrying
      phosphatidylinositol 4-kinase type 2 alpha (PI4KIIalpha) toward the PM of CD4(+)
      T cells. Hence, Rab27a promotes high levels of PM phosphatidylinositol 4
      phosphate and the localized production of PI(4,5)P2, therefore controlling
      Pr55(Gag) membrane association. Rab27a also controls PI(4,5)P2 levels at the
      virus-containing compartments of macrophages. By screening Rab27a effectors, we
      identified that Slp2a, Slp3, and Slac2b are required for the association of
      Pr55(Gag) with the PM and that Slp2a cooperates with Rab27a in the recruitment of
      PI4KIIalpha to the PM. We conclude that by directing the trafficking of
      PI4KIIalpha-positive endosomes toward the PM, Rab27a controls PI(4,5)P2
      production and, consequently, HIV-1 replication.

PMID- 25940348
TI  - Axonal autophagosomes recruit dynein for retrograde transport through fusion with
      late endosomes.
AB  - Efficient degradation of autophagic vacuoles (AVs) via lysosomes is an important
      cellular homeostatic process. This is particularly challenging for neurons
      because mature acidic lysosomes are relatively enriched in the soma. Although
      dynein-driven retrograde transport of AVs was suggested, a fundamental question
      remains how autophagosomes generated at distal axons acquire dynein motors for
      retrograde transport toward the soma. In this paper, we demonstrate that late
      endosome (LE)-loaded dynein-snapin complexes drive AV retrograde transport in
      axons upon fusion of autophagosomes with LEs into amphisomes. Blocking the fusion
      with syntaxin17 knockdown reduced recruitment of dynein motors to AVs, thus
      immobilizing them in axons. Deficiency in dynein-snapin coupling impaired AV
      transport ,: resulting in AV accumulation in neurites and synaptic terminals.
      Altogether, our study provides the first evidence that autophagosomes recruit
      dynein through fusion with LEs and reveals a new motor-adaptor sharing mechanism
      by which neurons may remove distal AVs engulfing aggregated proteins and
      dysfunctional organelles for efficient degradation in the soma.

PMID- 25940350
TI  - Sample Size Requirements for Traditional and Regression-Based Norms.
AB  - Test norms enable determining the position of an individual test taker in the
      group. The most frequently used approach to obtain test norms is traditional
      norming. Regression-based norming may be more efficient than traditional norming
      and is rapidly growing in popularity, but little is known about its technical
      properties. A simulation study was conducted to compare the sample size
      requirements for traditional and regression-based norming by examining the 95%
      interpercentile ranges for percentile estimates as a function of sample size,
      norming method, size of covariate effects on the test score, test length, and
      number of answer categories in an item. Provided the assumptions of the linear
      regression model hold in the data, for a subdivision of the total group into
      eight equal-size subgroups, we found that regression-based norming requires
      samples 2.5 to 5.5 times smaller than traditional norming. Sample size
      requirements are presented for each norming method, test length, and number of
      answer categories. We emphasize that additional research is needed to establish
      sample size requirements when the assumptions of the linear regression model are
      violated. 

PMID- 25940351
TI  - Practical considerations for the administration of glucarpidase in high-dose
      methotrexate (HDMTX) induced renal dysfunction.

PMID- 25940352
TI  - Tenofovir-based rescue therapy in chronic hepatitis B patients with suboptimal
      responses to adefovir with prior lamivudine resistance.
AB  - We evaluated the efficacy of tenofovir (TDF)-based rescue therapy and compared
      the outcomes of TDF monotherapy and TDF-based nucleoside analog (NA) combination
      therapy in patients with suboptimal response (SOR) to adefovir (ADV) with or
      without NAs in lamivudine (LAM)-resistant chronic hepatitis B. All study subjects
      received ADV with or without NAs due to prior LAM resistance, and were then
      switched to TDF-based rescue therapy due to SOR (hepatitis B virus DNA >20 IU/ml
      after at least 6 months of therapy). A total of 125 patients were eligible. The
      overall cumulative proportion of complete virologic response (CVR) was 64 of 74
      patients (86.5%) at 48 weeks of treatment. During the follow-up period of 48
      weeks, there was no significant difference in CVR rate (P = 0.750) between the
      TDF monotherapy (n = 18) and the TDF with NA groups (n = 107). Patients with ADV
      genotypic mutations showed inferior antiviral responses to TDF compared with the
      patients without ADV genotypic mutations, but this was not statistically
      significant (P = 0.069). Partial virological response to prior ADV therapy showed
      higher CVR rates compared to patients with non-response at 12 weeks (P = 0.013),
      but there was no significant difference after 24 (P = 0.076) and 48 weeks (P =
      0.198) of treatment. TDF monotherapy is as effective as TDF plus NA combination
      therapy in patients with SOR to ADV-based rescue therapy and LAM resistance. TDF,
      with or without NAs, was effective even in cases of ADV resistance.

PMID- 25940353
TI  - School-based and community-based actions for scaling-up diagnosis and treatment
      of schistosomiasis toward its elimination in an endemic area of Brazil.
AB  - This study evaluated a school-based and a community-based scheme for diagnosis,
      treatment and follow-up of schistosomiasis mansoni among school-aged children in
      views of resolution CD49.R19 of the Pan American Health Organization toward the
      elimination of schistosomiasis as a public health problem in the Americas and
      subsequent commitments endorsed by the Brazilian government. The school-aged
      population from a representative municipality of the endemic area of Northeastern
      Brazil was randomly allocated to either school-based or community-based scheme.
      The two schemes were compared with regard to coverage of diagnosis by the Kato
      Katz method (KK) at baseline, treatment of the positives for Schistosoma mansoni
      with praziquantel, treatment of the positives for soil-transmitted helminthes
      (STH) with mebendazole, as well as follow-up of treatment efficacy and
      reinfection assessed respectively at four and 12 months after treatment.
      Nutritional status of the positives for S. mansoni was assessed at baseline and
      re-assessed at 12 months after treatment. Coverage of diagnosis and treatment was
      satisfactory (>75%) in both schemes. Diagnosis coverage at baseline and at 12
      months was significantly higher in the community scheme, whereas treatment
      coverage did not differ significantly between the two schemes either at baseline
      or at 12 months. The number of children covered per day was significantly higher
      in the schools than in the community at baseline but not at follow-up, when daily
      coverage was higher in the community. With regard to S. mansoni, overall
      treatment efficacy rate at four months was 90.8%, and reinfection rate at 12
      months was 21.6%. For STH, overall treatment efficacy was 45.4% and reinfection,
      32.8%. The nutritional status of the positives for S. mansoni at baseline did not
      change significantly at 12 months post-treatment. Actions targeted at this
      particularly vulnerable high-risk group should combine school-based and community
      based interventions as well as preventive measures to reduce transmission. 

PMID- 25940355
TI  - Placental growth factor concentration in maternal circulation decreases after
      fetal death: lessons from a case series study.
AB  - PURPOSE: Placental growth factor (PlGF) has been suggested as a possible
      biomarker for major placenta-related disorders such as preeclampsia and
      intrauterine growth restriction. However, experimental findings suggest that PlGF
      concentrations may be influenced by other factors besides the placenta. In the
      present study, we examined how acute fetal injury affects PlGF concentrations in
      maternal circulation. We therefore monitored PlGF concentrations in maternal
      circulation before and after feticide. METHODS: A prospective comparative study
      was performed. Blood samples were drawn prospectively between January and July
      2012, before and after feticide at predetermined time points in relation to the
      procedure (0, 30, 60, and 120 min). The levels of lactate dehydrogenase (LDH) in
      the maternal circulation were measured to detect acute tissue damage. PlGF
      concentrations were measured by standard human ELISA. RESULTS: Following feticide
      (60 and 120 min), PlGF concentrations decreased significantly compared to the
      concentrations before feticide. LDH concentrations did not change before and
      after feticide. CONCLUSIONS: Our finding, along with the detailed review of the
      literature described in our work, supports a new concept in which primary fetal
      distress can affect PlGF concentration in maternal circulation. A large-scale
      study is required to strengthen our finding.

PMID- 25940356
TI  - Comparison between the different methods developed for determining the onset of
      the LH surge in urine during the human menstrual cycle.
AB  - PURPOSE: To determine whether an optimal method exists for the detection of the
      luteinising hormone (LH) surge onset in research datasets of urinary hormonal
      profiles of menstrual cycles. METHODS: The scientific literature was searched to
      compare published methodologies for detection of the LH surge onset in urine.
      Their performance was tested using complete hormonal profiles from 254 ovulatory
      cycles from 227 women attempting pregnancy (normal regular menstrual cycles; no
      known infertility). RESULTS: Three major methodologies to determine the onset of
      the LH surge in urine were identified. The key difference between these methods
      is how the cycle days that contribute to LH baseline assessment are determined:
      using fixed days (method #1), based on peak LH day (method #2), based on a
      provisional estimate of the LH surge (method #3). Method #1 requires no prior
      cycle information, whereas methods #2 and #3 need to consider complete cycle
      data. The most reliable method for calculation of baseline LH was using 2 days
      before the estimated surge day, plus the previous 4/5 days. CONCLUSIONS:
      Different methods for identification of the urinary LH surge can provide very
      different determinations of LH surge day, thus care must be taken when comparing
      between studies that apply different methodologies. The optimal method for
      determining the onset of the LH surge in urine requires retrospective estimation
      of day of LH surge to identify the most appropriate part of the cycle to consider
      as the baseline. This method can be adopted for application in population
      studies.

PMID- 25940354
TI  - Differences in the Epidemiology of Human Cases of Avian Influenza A(H7N9) and
      A(H5N1) Viruses Infection.
AB  - BACKGROUND: The pandemic potential of avian influenza viruses A(H5N1) and A(H7N9)
      remains an unresolved but critically important question. METHODS: We compared the
      characteristics of sporadic and clustered cases of human H5N1 and H7N9 infection,
      estimated the relative risk of infection in blood-related contacts, and the
      reproduction number (R). RESULTS: We assembled and analyzed data on 720 H5N1
      cases and 460 H7N9 cases up to 2 November 2014. The severity and average age of
      sporadic/index cases of H7N9 was greater than secondary cases (71% requiring
      intensive care unit admission vs 33%, P = .007; median age 59 years vs 31, P <
      .001). We observed no significant differences in the age and severity between
      sporadic/index and secondary H5N1 cases. The upper limit of the 95% confidence
      interval (CI) for R was 0.12 for H5N1 and 0.27 for H7N9. A higher proportion of
      H5N1 infections occurred in clusters (20%) compared to H7N9 (8%). The relative
      risk of infection in blood-related contacts of cases compared to unrelated
      contacts was 8.96 for H5N1 (95% CI, 1.30, 61.86) and 0.80 for H7N9 (95% CI, .32,
      1.97). CONCLUSIONS: The results are consistent with an ascertainment bias towards
      severe and older cases for sporadic H7N9 but not for H5N1. The lack of evidence
      for ascertainment bias in sporadic H5N1 cases, the more pronounced clustering of
      cases, and the higher risk of infection in blood-related contacts, support the
      hypothesis that susceptibility to H5N1 may be limited and familial. This analysis
      suggests the potential pandemic risk may be greater for H7N9 than H5N1.

PMID- 25940357
TI  - Relationship of ABO Blood Type on Rotator Cuff Tears.
AB  - BACKGROUND: ABO blood groups are associated with various diseases. A relationship
      between Achilles tendon ruptures and blood type O has been reported, although its
      pathogenesis was not clear. To the best of our knowledge, there is no published
      study describing the relationship between blood type and rotator cuff tendon
      tears. OBJECTIVE: To determine whether patients with rotator cuff tear had a
      greater prevalence of blood type O than those without rotator cuff tear. DESIGN:
      A cross-sectional study. SETTING: Research hospital outpatient evaluation.
      PARTICIPANTS: A total of 316 subjects with shoulder pain were included and
      divided into "tear" and "no-tear" groups according to ultrasonographic
      examination. MAIN OUTCOME MEASURES: ABO blood group, gender, dominant arm,
      smoking history, trauma history, and age were compared between the 2 groups and
      the odds ratios of these factors were evaluated by logistic regression. RESULTS:
      The tear group (38.6%) had more instances of blood type O than the healthy
      population (27.2%; P = .002). The adjusted odds ratio for rotator cuff tear for
      blood type O to non-O was 2.38 (95% confidence interval 1.28-4.42). The odds
      ratios for rotator cuff tears for smoking, major trauma history, minor trauma
      history, and age were 2.08, 3.11, 2.29, and 1.06, respectively. CONCLUSION:
      Patients with rotator cuff tears were more likely to have blood type O. The odds
      ratios of factors for rotator cuff tears were high in the following order: major
      trauma history, blood type O, minor trauma history, and age.

PMID- 25940358
TI  - Cardiac Metastasis from Breast Cancer as an Initial Focus of Recurrence.

PMID- 25940359
TI  - Color Doppler Ultrasound Follow-Up of Infantile Hemangiomas and Peripheral
      Vascularity in Patients Treated with Propranolol.
AB  - BACKGROUND: Infantile hemangiomas (IHs) are the most common vascular tumors in
      childhood. Diagnosis of IHs is usually clinical, however, to determine the actual
      dimensions of the lesion or the anatomic changes that occur during its evolution
      and treatment, a color Doppler ultrasound (CDU) examination can be performed. To
      date, there are few publications that assess the sonographic response to
      propranolol in IHs, and to our knowledge, none that consider simultaneous
      evaluation of both intralesional and normal peripheral blood vessels in these
      cases. OBJECTIVE: Evaluation of the anatomic effect of propranolol in IHs and
      peripheral blood vessels using CDU. METHODS: A cohort study was performed in 10
      pediatric patients with a diagnosis of IH in whom systemic therapy with
      propranolol was indicated. The patients underwent a baseline and 3-month follow
      up CDUs of the tumor and the main peripheral vessels of the right upper
      extremity. RESULTS: The group was composed of 7 (70%) girls and 3 (30%) boys. The
      average CDU decrease in size of the longitudinal axis was 11%; of the transverse
      axis, 24%; tumor thickness, 30%; and intralesional vessel thickness, 46%.
      Hemangioma volume measured by CDU decreased an average of 51%. The thickness of
      the peripheral vessels did not change significantly between the baseline and 3
      month follow-up CDUs. CONCLUSION: CDU permits noninvasive quantification of the
      changes in IHs and peripheral vessels in patients receiving propranolol therapy.
      In our cohort of cases there was a significant reduction in tumor volume;
      however, peripheral vascularity was not significantly affected.

PMID- 25940360
TI  - Are radiologists ready for higher value care?

PMID- 25940361
TI  - Through a glass darkly.

PMID- 25940362
TI  - Nationwide price variability for an elective, outpatient imaging procedure.
AB  - PURPOSE: Out-of pocket expenses for common medical tests and procedures will
      become increasingly relevant as high-deductible insurance plans gain widespread
      adoption. The purpose of this study was to determine the variability of pricing
      for an outpatient, noncontrast knee MRI, based on geographic location and
      population. METHODS: We randomly chose nonhospital outpatient radiology centers
      in each state's highest-population locality, based on a list generated from the
      ACR MRI Accreditation Program database. The presence of >=2 and a maximum of 3
      centers within a given locality was required for inclusion. Using a standardized
      script, we contacted centers by phone to determine the lowest, out-of-pocket,
      bundled cost (technical fee plus professional fee). The median (interquartile
      range) costs were calculated within each locality and region, including Midwest,
      Northeast, South, and West regions. A generalized linear model and Spearman's
      rank correlation were used to determine the association between cost and region,
      and cost and population, respectively. RESULTS: A total of 122 outpatient centers
      from 43 cities were analyzed. Costs ranged from $259 to $2,042 across all
      centers. For centers within a locality, the difference between the minimum and
      maximum costs among centers ranged from $1,592 to $0; median cost differences
      between localities ranged from $1,488 to $325. Median cost for the West,
      Northeast, Midwest, and South region was $690, $500, $550, and $550, respectively
      (P = .849). Median cost was inversely correlated with population density (rho = 
      0.417 [correlation coefficient], P = .005). CONCLUSIONS: Out-of-pocket costs for
      an outpatient knee MRI vary substantially across imaging centers, both locally
      and nationally. Cost tends to decrease with increasing local population.

PMID- 25940364
TI  - Management in the media age: lessons for radiology from the world of television
      and music.

PMID- 25940363
TI  - 2014 RAD-AID Conference on International Radiology for Developing Countries: The
      Road Ahead for Global Health Radiology.

PMID- 25940365
TI  - Operator radiation dose reduction during fluoroscopic interventional procedures.

PMID- 25940366
TI  - Adding value as young radiologists: challenges and opportunities, part 1.

PMID- 25940367
TI  - Re: "CT Training of Nuclear Medicine Residents in the United States, 2013-2014".

PMID- 25940368
TI  - Authors' reply.

PMID- 25940369
TI  - Strong selection on male plumage in a hybrid zone between a hybrid bird species
      and one of its parents.
AB  - Homoploid hybrid speciation (HHS) requires reproductive barriers between hybrid
      and parent species, despite incomplete reproductive isolation (RI) between the
      parents. Novel secondary sexual trait values in hybrids may cause prezygotic
      isolation from both parents, whereas signals inherited by the hybrid from one
      parent species may cause prezygotic isolation with the other. Here we investigate
      whether differences in male plumage function as a premating barrier between the
      hybrid Italian sparrow and one of its parent species, the house sparrow, in a
      narrow Alpine hybrid zone. Italian sparrow male plumage is a composite mosaic of
      the parental traits, with its head plumage most similar to its other parent, the
      Spanish sparrow. We use geographical cline analysis to examine selection on three
      plumage traits, 75 nuclear single nucleotide polymorphisms (SNPs) and hybrid
      indices based on these SNPs. Several SNPs showed evidence of restricted
      introgression in the Alps, supporting earlier findings. Crown colour exhibited
      the narrowest plumage cline, representing a 37% (range 4-65%) drop in fitness.
      The cline was too narrow to be due to neutral introgression. Only crown colour
      was significantly bimodal in the hybrid zone. Bimodality may be due to RI or a
      major QTL, although fitness estimates suggest that selection contributes to the
      pattern. We discuss the implications with respect to HHS and the species status
      of the Italian sparrow. 

PMID- 25940370
TI  - Age-dependent alteration of transgene expression and cytomegalovirus promoter
      methylation in transgenic cloned and recloned dogs.

PMID- 25940372
TI  - Impact of donor weight in pediatric liver transplantation.

PMID- 25940371
TI  - Synergistic antiproliferative effect of imatinib and adriamycin in platelet
      derived growth factor receptor-expressing osteosarcoma cells.
AB  - Osteosarcoma (OS) is the most frequent primary solid malignant tumor of bone. Its
      prognosis remains poor in the substantial proportion of patients who do not
      respond to chemotherapy and novel therapeutic options are therefore needed. We
      previously established a mouse model that mimics the aggressive behavior of human
      OS. Enzyme-linked immunosorbent assay-based screening of such mouse tumor lysates
      identified platelet-derived growth factor-BB (PDGF-BB) as an abundant soluble
      factor, the gene for which was expressed dominantly in surrounding non-malignant
      cells of the tumor, whereas that for the cognate receptor (PDGF receptor beta)
      was highly expressed in OS cells. Platelet-derived growth factor-BB induced
      activation of both MEK-ERK and phosphatidylinositol 3-kinase-protein kinase B
      signaling pathways and promoted survival in OS cells deprived of serum, and these
      effects were blocked by the PDGF receptor inhibitor imatinib. However, these
      actions of PDGF-BB and imatinib were mostly masked in the presence of serum.
      Whereas imatinib alone did not manifest an antitumor effect in mice harboring OS
      tumors, combined treatment with imatinib and adriamycin exerted a synergistic
      antiproliferative effect on OS cells in vivo. These results suggest that
      treatment of OS with imatinib is effective only when cell survival is dependent
      on PDGF signaling or when imatinib is combined with another therapeutic
      intervention that renders the tumor cells susceptible to imatinib action, such as
      by inducing cellular stress.

PMID- 25940373
TI  - Emergence of naturally occurring scaffolds for cell transplantation in type 1
      diabetes.

PMID- 25940374
TI  - Longitudinal stability of medication adherence: Trying to decipher an important
      construct.

PMID- 25940375
TI  - Prognostic Value of a Very Prolonged Asystole during Head-Up Tilt Test.
AB  - BACKGROUND: Clinical significance and prognosis of a cardioinhibitory response to
      head-up tilt (HUT) test with a very prolonged asystole (>=30 seconds) is poorly
      studied. Our aim was to evaluate the treatment (including pacemaker implantation)
      and prognosis (syncope recurrence, syncope-related trauma, and overall mortality)
      of patients with a very prolonged asystole on a HUT test. METHODS AND RESULTS: A
      retrospective study was conducted in two centers between January 2003 and
      December 2013 and included a total of 2,263 consecutive HUT tests (sensitized
      with isosorbide dinitrate) performed in 2,247 patients with syncope of unknown
      etiology. Cardioinhibitory response with asystole was observed in 149 (6.6%) of
      these tests (44.3% women, mean age 37 +/- 18 years old, 16.1% in the
      nonpharmacological phase), with a median duration of asystole of 10 (6-19)
      seconds. Very prolonged asystole (>=30 seconds) was documented in 11 (0.5%)
      patients (45% women; mean age 40 +/- 19 years; only one in the nonpharmacological
      phase, 9 minutes after HUT). The longest pause lasted 63 seconds. In all
      patients, avoidance of triggering factors and physical counterpressure maneuvers
      were recommended. Telephone follow-up was performed: in one patient,
      fludrocortisone was started; tilt training was conducted in one patient and none
      received a pacemaker. After a median follow-up of 42 (30-76) months, four
      patients (36%) had syncopal recurrences, one patient had a syncope-related injury
      (scalp laceration), and no patient died.

PMID- 25940376
TI  - Transcriptome of early embryonic invasion at implantation sites in a murine
      model.
AB  - Successful implantation relies on the interaction between a competent embryo and
      a receptive endometrium. The aim of the present study was to investigate genes
      differentially expressed in early invasive embryonic tissue versus decidual
      tissue in mice. Samples were obtained from the ectoplacental cone, the
      immediately surrounding deciduas and from deciduas from interimplantation sites.
      Microarray analysis showed that 817 genes were differentially expressed between
      extra-embryonic tissue and the surrounding decidua and that 360 genes were
      differentially expressed between the different deciduas, with a high
      representation of developmental processes. Genes differentially expressed in the
      maternal compartment included chemokines, lipoproteins, growth factors and
      transcription factors, whereas the embryonic invasive tissue expressed genes
      commonly observed in invasive tumour-like processes. These results provide
      information about genes involved in early embryonic invasion and the control
      exerted by the surrounding decidua. This information may be useful to find
      targets involved in pathologies associated with implantation failure and early
      pregnancy loss.

PMID- 25940377
TI  - Cytotoxic chemotherapy for pancreatic neuroendocrine tumors.
AB  - Advanced neuroendocrine tumors are incurable, and most patients will succumb to
      the disease. Chemotherapies with cytotoxic agents such as streptozocin, 5
      fluorouracil, or temozolomide have been frequently used as drug therapies for
      neuroendocrine tumors. Streptozocin, which is the only approved cytotoxic agent
      available for the treatment of this disease in many countries, has been
      considered a key agent for the treatment of advanced neuroendocrine tumors based
      on the results of phase III studies. However, the widespread acceptance of
      streptozocin-based chemotherapy for this indication has been limited by concerns
      regarding toxicity. Recent prospective and retrospective studies showed the
      promising activity of a temozolomide-based regimen, although an adequate
      prospective controlled study defining the role of temozolomide in the treatment
      of neuroendocrine tumors is lacking. The promising activity of cytotoxic agents
      awaits confirmation; solid evidence-based recommendations and treatment decisions
      are needed for the optimal use of chemotherapy against this disease. 

PMID- 25940378
TI  - Increase in the titer of lentiviral vectors expressing potassium channels by
      current blockade during viral vector production.
AB  - BACKGROUND: High titers of lentiviral vectors are required for the efficient
      transduction of a gene of interest. During preparation of lentiviral the vectors,
      the protein of interest is inevitably expressed in the viral vector-producing
      cells. This expression may affect the production of the lentiviral vector.
      METHODS: We prepared lentiviral vectors expressing inwardly rectifying potassium
      channel (Lv-Kir2.1), its dominant-negative form (Lv-Kir-DN), and other K(+)
      channels, using the ubiquitously active beta-actin and neuron-specific synapsin I
      promoters. RESULTS: The titer of Lv-Kir-DN was higher than that of Lv-Kir2.1,
      suggesting a negative effect of induced K(+) currents on viral titer. We then
      blocked Kir2.1 currents with the selective blocker Ba(2+) during Lv-Kir2.1
      production, and obtained about a 5-fold increase in the titer. Higher
      extracellular K(+) concentrations increased the titer of Lv-Kir2.1 about 9-fold.
      With a synapsin I promoter Ba(2+) increased the titer because of the moderate
      expression of Kir2.1 channel. Channel blockade also increased the titers of the
      lentivirus expressing Kv1.4 and TREK channels, but not HERG. The increase in
      titer correlated with the K(+) currents generated by the channels expressed.
      CONCLUSION: In the production of lentivirus expressing K(+) channels, titers are
      increased by blocking K(+) currents in the virus-producing cells. This identifies
      a crucial issue in the production of viruses expressing membrane channels, and
      should facilitate basic and gene therapeutic research on channelopathies.

PMID- 25940379
TI  - Functional and structural comparisons of the arthroscopic knotless double-row
      suture bridge and single-row repair for anterosuperior rotator cuff tears.
AB  - BACKGROUND: We compared the outcomes of knotless double-row suture bridge and
      single-row repairs in patients undergoing arthroscopic repair for anterosuperior
      rotator cuff tears. METHODS: We included 61 full-thickness anterosuperior rotator
      cuff tears treated by arthroscopic repair, namely, single-row repair (group 1: 25
      shoulders; mean patient age, 64 years) and the knotless double-row suture bridge
      repair (group 2: 36 shoulders; mean patient age, 62 years). Preoperative and
      postoperative magnetic resonance imaging was performed for all shoulders.
      Clinical outcomes were evaluated for mean follow-up periods of 81 months (range,
      72-96 months) in group 1 and 34 months (range, 24-42 months) in group 2, using
      the University of California, Los Angeles and Japanese Orthopaedic Association
      assessments. RESULTS: At the final follow-up, both groups showed improvement in
      the average University of California, Los Angeles and Japanese Orthopaedic
      Association scores and range of motion, although no intergroup differences were
      observed. Both groups showed improved abduction strength, and the average score
      was higher in group 2 (P = .0112). The lift-off and belly-press test results were
      improved in both groups. Postoperatively, the incidence of positive lift-off
      tests tended to be lower (P = .075) and that of positive belly-press tests was
      lower in group 2, P = .049). The repair failure rate tended to be lower in group
      2 (14% [5 of 36]) than in group 1 (32% [8 of 25]; P = .0839). CONCLUSIONS:
      Arthroscopic knotless double-row suture bridge repair of anterosuperior rotator
      cuff tears yielded functional outcomes equivalent to those of single-row repair
      and may be useful for improving subscapularis function, abduction strength, and
      tendon healing.

PMID- 25940380
TI  - Intraobserver and interobserver agreement of Goutallier classification applied to
      magnetic resonance images.
AB  - BACKGROUND: Fatty infiltration of the muscle bellies is an important prognostic
      factor in rotator cuff tears. It was described initially in computed tomography
      examinations, and there is an ongoing debate about whether magnetic resonance
      (MR) is a reliable method for staging fatty infiltration. This study sought to
      determine intraobserver and interobserver agreement for Goutallier's
      classification of fatty infiltration of the rotator cuff as evaluated through MR
      imaging. MATERIALS AND METHODS: Twenty MR examinations of the shoulder showing
      full-thickness tear of the supraspinatus tendon, with or without associated
      lesions, were evaluated by 3 radiologists with experience in musculoskeletal
      system imaging and 3 fellowship-trained shoulder surgeons. The evaluators
      classified the fatty infiltration of the supraspinatus muscle according to the
      guidelines proposed by Goutallier et al. After 8 weeks, they re-evaluated the
      examinations, without access to their previous reports. Weighted kappa index
      values were determined for intraobserver and interobserver agreement analyses,
      and intraobserver agreement kappa values are reported with 95% confidence
      intervals (CIs). RESULTS: The mean intraobserver agreement was 0.832 among the
      orthopedists (CI > 95%) and 0.741 among the radiologists (CI > 95%).
      Interobserver agreement was 0.8214 (evaluation 1) and 0.7231 (evaluation 2) among
      the orthopedists (P < .0001) and 0.6627 (evaluation 1) and 0.6067 (evaluation 2)
      among the radiologists (P < .0001). Intraobserver agreement was not associated
      with length of experience or frequency of routine evaluations. CONCLUSIONS: When
      it is applied to MR images of rotator cuff musculature, Goutallier's fatty
      infiltration staging rubric yielded highly significant intraobserver and
      interobserver agreement.

PMID- 25940381
TI  - The extended medial elbow approach-a cadaveric study.
AB  - BACKGROUND: The two most commonly used approaches to expose medial elbow
      structures are the flexor carpi ulnaris split and the Hotchkiss over-the-top
      approach. The aim of this study was to define the extended medial approach to the
      elbow, featuring advantages of over-the-top (proximal exposure) and additional
      complete exposure of the coronoid and proximal medial ulna, while respecting the
      internervous plane between the flexor pronator mass and flexor carpi ulnaris
      muscle. METHODS: In this comparative anatomic study, 12 fresh frozen cadaveric
      elbows were dissected alternately to study the distal limitation and exposed area
      of the extended medial elbow approach compared with splitting the flexor carpi
      ulnaris. RESULTS: Proximal ulna exposure area was comparable between the extended
      medial elbow approach (average, 840 mm(2)) and the flexor carpi ulnaris split
      (average, 810 mm(2); P = .44). The extended medial approach was limited distally
      by the posterior recurrent ulnar artery (mean 68 mm from medial epicondyle),
      whereas the first motor branch for the flexor carpi ulnaris muscle limited the
      second approach in 75% of the specimens (mean 29 mm from medial epicondyle, P <
      .001). CONCLUSIONS: The extended medial elbow approach is a single approach
      allowing full exposure of the medial elbow and combining the advantages of the
      over-the-top approach with a safe distal extension to the medial ulna. In
      contrast to the flexor carpi ulnaris split, our approach respects the
      internervous plane.

PMID- 25940382
TI  - Propionibacterium acnes-mediated distal clavicular osteolysis: a case report.

PMID- 25940383
TI  - Is an extension of the safe zone possible without jeopardizing the proximal
      radioulnar joint when performing a radial head plate osteosynthesis?
AB  - BACKGROUND: Proximal radial fractures are common elbow injuries. Because of the
      fracture pattern, stability criteria, or plate configuration, a plate position
      outside the "safe zone" (SZ) may be required in some cases when performing a
      radial head plate osteosynthesis. We examined the gross anatomy of the radial
      head and analyzed different so-called low-profile and precontoured radial head
      and neck plates with respect to the SZ. MATERIALS AND METHODS: Macroscopic
      measurements of the radial head and neck of 22 formalin-fixed human cadaveric
      upper extremities were obtained. The SZ was determined by maximum forearm
      rotation. If the edge of a plate could be extended beyond the respective SZ
      boundary without jeopardizing the proximal radioulnar joint (PRUJ) in maximum
      forearm rotation, a new plate-specific SZ boundary was set. RESULTS: The mean SZ
      was 133 degrees  (SD, 14 degrees ). Among the 5 plates studied, only the 2 radial
      neck designs allowed the anterior edge of the plate to partially pass the lesser
      sigmoid notch of the ulna and consequently afforded a significant extension of
      the SZ in maximum pronation. All 3 radial head designs had to remain within the
      SZ to avoid interference with the PRUJ. A safe plate position depends on
      individual plate dimensions, particularly the proximal plate width, and the
      diameter of the radial head. The smaller the head diameter, the more accurately a
      plate must be placed within the SZ. CONCLUSIONS: If an extension of the SZ in
      radial head plate osteosynthesis is not essential, we recommend respecting the SZ
      to minimize the possibility of interference with the PRUJ.

PMID- 25940384
TI  - Dissecting genetic and environmental mutation signatures with model organisms.
AB  - Deep sequencing has impacted on cancer research by enabling routine sequencing of
      genomes and exomes to identify genetic changes associated with carcinogenesis.
      Researchers can now use the frequency, type, and context of all mutations in
      tumor genomes to extract mutation signatures that reflect the driving mutational
      processes. Identifying mutation signatures, however, may not immediately suggest
      a mechanism. Consequently, several recent studies have employed deep sequencing
      of model organisms exposed to discrete genetic or environmental perturbations.
      These studies exploit the simpler genomes and availability of powerful genetic
      tools in model organisms to analyze mutation signatures under controlled
      conditions, forging mechanistic links between mutational processes and
      signatures. We discuss the power of this approach and suggest that many such
      studies may be on the horizon. 

PMID- 25940385
TI  - Synthesis of pretubulysin-derivatives via the TubUgi-approach.
AB  - The Ugi reaction is found to be a very powerful tool for the synthesis of
      (pre)tubulysin derivatives, allowing the introduction of various functionalized
      side chains in only one step. While polar groups such as amides are not well
      tolerated, unpolar side chains such as allyl or propargyl ether are well
      accepted. These functionalities also allow subsequent modifications in the side
      chain, e.g. via ring closing metathesis or Click reaction. 

PMID- 25940386
TI  - Impact of an Emergency Triage Assessment and Treatment (ETAT)-based triage
      process in the paediatric emergency department of a Guatemalan public hospital.
AB  - BACKGROUND: Triage process implementation has been shown to be effective at
      improving patient outcomes. This study sought to develop, implement and assess
      the impact of an Emergency Triage Assessment and Treatment (ETAT)-based emergency
      triage process in the paediatric emergency department (PED) of a public hospital
      in Guatemala. METHODS: The study was a quality improvement comparison with a
      before/after design. Uptake was measured by percentage of patients with an
      assigned triage category. Outcomes were hospital admission rate, inpatient length
      of stay (LOS), and mortality as determined by two distinct medical record reviews
      for 1 year pre- and post-intervention: a random sample (RS) of all PED patients
      and records for all critically-ill (CI) children [serious diagnoses or admission
      to the paediatric intensive care unit (PICU)]. Demographics, diagnoses and
      disposition were recorded. RESULTS: The RS totalled 1027 (51.4% male); median
      ages pre- and post-intervention were 2.0 and 2.4 years, respectively. There were
      196 patients in the CI sample, of whom 56.6% were male and one-third were
      neonates; median ages of the CI group pre- and post-intervention were 3.1 and 5.6
      months, respectively. One year after implementation, 97.5% of medical records had
      been assigned triage categories. Triage categories (RS/CI) were: emergency
      (2.9%/54.6%), priority (47.6%/44.4%) and non-urgent (49.4%/1.0%). The CI group
      was more frequently diagnosed with shock (25%/1%), seizures (9%/0.5%) and
      malnutrition (6%/0.5%). Admission rates for the RS (8% vs 4%, P=0.01) declined
      after implementation. For the CI sample, admission rate to the PICU (47% vs 24%,
      P=0.002) decreased and LOS (7.3 vs 5.7 days, P=0.09) and mortality rates (12% vs
      6%, P=0.15) showed trends toward decreasing post-implementation. CONCLUSIONS:
      Paediatric-specific triage algorithms can be implemented and sustained in
      resource-limited settings. Significant decreases in admission rates (both overall
      and for the PICU) and trends towards decreased LOS and mortality rates of
      critically ill children suggest that ETAT-based triage systems have the potential
      to greatly improve patient care in Latin America.

PMID- 25940390
TI  - Intensive walking exercise for lower extremity peripheral arterial disease: A
      systematic review and meta-analysis.
AB  - BACKGROUND: Supervised treadmill exercise is the recommended therapy for
      peripheral arterial disease (PAD) patients with intermittent claudication (IC).
      However, most PAD patients do not exhibit typical symptoms of IC. The aim of the
      present study was to explore the efficacy and safety of intensive walking
      exercise in PAD patients with and without IC. METHODS: The PubMed, Embase and
      Cochrane Library databases were systematically searched. Randomized controlled
      trials comparing the effects of intensive walking exercise with usual care in
      patients with PAD were included for systematic review and meta-analysis. RESULTS:
      Eighteen trials with 1200 patients were eligible for the present analysis.
      Compared with usual care, intensive walking exercise significantly improved the
      maximal walking distance (MWD), pain-free walking distance, and the 6-min walking
      distance in patients with PAD (P < 0.00001 for all). Subgroup analyses indicated
      that a lesser improvement in MWD was observed in the subgroup with more diabetes
      patients, and that the subgroup with better baseline walking ability exhibited
      greater improvement in walking performance. In addition, similar improvements in
      walking performance were observed for exercise programs of different durations
      and modalities. No significant difference was found in adverse events between the
      intensive walking and usual care groups (relative risk 0.84; 95% confidence
      interval 0.51, 1.39; P = 0.50). CONCLUSIONS: Regardless of exercise length and
      modality, regularly intensive walking exercise improves walking ability in PAD
      patients more than usual care. The presence of diabetes may attenuate the
      improvements in walking performance in patients with PAD following exercise.

PMID- 25940392
TI  - MRI investigation of water-oil two phase flow in straight capillary, bifurcate
      channel and monolayered glass bead pack.
AB  - The study of immiscible fluid displacement between aqueous-phase liquids and non
      aqueous-phase liquids in porous media is of great importance to oil recovery,
      groundwater contamination, and underground pollutant migration. Moreover, the
      attendant viscous, capillary, and gravitational forces are essential to
      describing the two-phase flows. In this study, magnetic resonance imaging was
      used to experimentally examine the detailed effects of the viscous, capillary,
      and gravitational forces on water-oil flows through a vertical straight
      capillary, bifurcate channel, and monolayered glass-bead pack. Water flooding
      experiments were performed at atmospheric pressure and 37.8 degrees C, and the
      evolution of the distribution and saturation of the oil as well as the
      characteristics of the two-phase flow were investigated and analyzed. The results
      showed that the flow paths, i.e., the fingers of the displacing phase, during the
      immiscible displacement in the porous medium were determined by the viscous,
      capillary, and gravitational forces as well as the sizes of the pores and
      throats. The experimental results afford a fundamental understanding of
      immiscible fluid displacement in a porous medium. 

PMID- 25940391
TI  - Improved respiratory navigator gating for thoracic 4D flow MRI.
AB  - BACKGROUND: Thoracic and abdominal 4D flow MRI is typically acquired in
      combination with navigator respiration control which can result in highly
      variable scan efficiency (Seff) and thus total scan time due to inter-individual
      variability in breathing patterns. The aim of this study was to test the
      feasibility of an improved respiratory control strategy based on diaphragm
      navigator gating with fixed Seff, respiratory driven phase encoding, and a
      navigator training phase. METHODS: 4D flow MRI of the thoracic aorta was
      performed in 10 healthy subjects at 1.5T and 3T systems for the in-vivo
      assessment of aortic time-resolved 3D blood flow velocities. For each subject,
      four 4D flow scans (1: conventional navigator gating, 2-4: new implementation
      with fixed Seff =60%, 80% and 100%) were acquired. Data analysis included semi
      quantitative evaluation of image quality of the 4D flow magnitude images (image
      quality grading on a four point scale), 3D segmentation of the thoracic aorta,
      and voxel-by-voxel comparisons of systolic 3D flow velocity vector fields between
      scans. RESULTS: Conventional navigator gating resulted in variable Seff=74+/-13%
      (range=56%-100%) due to inter-individual variability of respiration patterns. For
      scans 2-4, the new navigator implementation was able to achieve predictable total
      scan times with stable Seff, only depending on heart rate. Semi- and fully
      quantitative analysis of image quality in 4D flow magnitude images was similar
      for the new navigator scheme compared to conventional navigator gating. For
      aortic systolic 3D velocities, good agreement was found between all new navigator
      settings (scan 2-4) with the conventional navigator gating (scan 1) with best
      performance for Seff=80% (mean difference=-0.01 m/s; limits of agreement=0.23
      m/s, Pearson's rho=0.89, p<0.001). No significant differences for image quality
      or 3D systolic velocities were found for 1.5T compared to 3T. CONCLUSIONS: The
      findings of this study demonstrate the feasibility of the new navigator scheme to
      acquire 4D flow data with more predictable scan time while maintaining image
      quality and 3D velocity information, which may prove beneficial for clinical
      applications.

PMID- 25940393
TI  - Enantioselective adsorption in homochiral metal-organic frameworks: the pore size
      influence.
AB  - Uptake experiments in thin films of isoreticular chiral MOFs of type
      Cu2(Dcam)2(L) with identical stereogenic centers but different pore dimensions
      show that the enantioselectivity is significantly influenced by the pore size.
      The highest selectivity was found for medium pore sizes, roughly corresponding to
      the extension of the chiral guest molecule, limonene. 

PMID- 25940395
TI  - Engineering the electronic bandgaps and band edge positions in carbon-substituted
      2D boron nitride: a first-principles investigation.
AB  - Modification of graphene to open a robust gap in its electronic spectrum is
      essential for its use in field effect transistors and photochemistry
      applications. Inspired by recent experimental success in the preparation of
      homogeneous alloys of graphene and boron nitride (BN), we consider here
      engineering the electronic structure and bandgap of C2xB1-xN1-x alloys via both
      compositional and configurational modification. We start from the BN end-member,
      which already has a large bandgap, and then show that (a) the bandgap can in
      principle be reduced to about 2 eV with moderate substitution of C (x < 0.25);
      and (b) the electronic structure of C2xB1-xN1-x can be further tuned not only
      with composition x, but also with the configuration adopted by C substituents in
      the BN matrix. Our analysis, based on accurate screened hybrid functional
      calculations, provides a clear understanding of the correlation found between the
      bandgap and the level of aggregation of C atoms: the bandgap decreases most when
      the C atoms are maximally isolated, and increases with aggregation of C atoms due
      to the formation of bonding and anti-bonding bands associated with hybridization
      of occupied and empty defect states. We determine the location of valence and
      conduction band edges relative to vacuum and discuss the implications on the
      potential use of 2D C2xB1-xN1-x alloys in photocatalytic applications. Finally,
      we assess the thermodynamic limitations on the formation of these alloys using a
      cluster expansion model derived from first-principles. 

PMID- 25940394
TI  - 3D Structural Fluctuation of IgG1 Antibody Revealed by Individual Particle
      Electron Tomography.
AB  - Commonly used methods for determining protein structure, including X-ray
      crystallography and single-particle reconstruction, often provide a single and
      unique three-dimensional (3D) structure. However, in these methods, the protein
      dynamics and flexibility/fluctuation remain mostly unknown. Here, we utilized
      advances in electron tomography (ET) to study the antibody flexibility and
      fluctuation through structural determination of individual antibody particles
      rather than averaging multiple antibody particles together. Through individual
      particle electron tomography (IPET) 3D reconstruction from negatively-stained ET
      images, we obtained 120 ab-initio 3D density maps at an intermediate resolution
      (~1-3 nm) from 120 individual IgG1 antibody particles. Using these maps as a
      constraint, we derived 120 conformations of the antibody via structural flexible
      docking of the crystal structure to these maps by targeted molecular dynamics
      simulations. Statistical analysis of the various conformations disclosed the
      antibody 3D conformational flexibility through the distribution of its domain
      distances and orientations. This blueprint approach, if extended to other
      flexible proteins, may serve as a useful methodology towards understanding
      protein dynamics and functions. 

PMID- 25940396
TI  - Low Molecular Weight Heparin (LMWH)-Induced Bullous Hemorrhagic Dermatosis.
AB  - Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are
      associated with side effects including hematomas, skin necrosis, contact
      dermatitis, and urticaria. We present a patient awaiting bypass surgery who
      developed bullous hemorrhagic dermatosis following LMWH.

PMID- 25940399
TI  - Correlation Between Changes in Tibial Tuberosity-Trochlear Groove Distance and
      Patellar Position During Active Knee Extension on Dynamic Kinematic Computed
      Tomographic Imaging.
AB  - PURPOSE: The purpose of this study was to evaluate changes in tibial tuberosity
      trochlear groove (TTTG) distance with knee flexion in patients with patellar
      instability and correlate it with patellar position. METHODS: Patients with
      symptomatic patellar instability underwent dynamic kinematic computed tomography
      (CT) during a cycle of knee extension from flexion. Knee flexion angles and
      corresponding TTTG distances, bisect offset, and patellar tilt were measured. Of
      the 51 knees, 37 had data available for interpolation between 5 degrees  and 30
      degrees . Results were interpolated to standardized intervals between 5 degrees 
      and 30 degrees  of knee flexion. Repeated-measures analysis (to identify
      differences between TTTG measurements at various knee flexion angles) and linear
      regression models (to assess for correlations between TTTG distance and bisect
      offset and between TTTG distance and patellar tilt) were used. RESULTS: Fifty-one
      symptomatic knees in 38 patients were available for analysis. Bisect offset and
      patellar tilt correlated significantly (P < .001) with TTTG distance over all
      flexion angles. Interpolated results for comparison resulted in 37 knees in which
      the mean TTTG distance of 17.2 +/- 5.8 mm at 5 degrees  decreased to 15.5 +/-
      5.7, 13.0 +/- 5.5, and 11.5 +/- 4.9 mm at 10 degrees , 20 degrees , and 30
      degrees  of knee flexion, respectively. Mean TTTG at 5 degrees  was 1.5 times
      greater than that at 30 degrees  (P < .001). At 5 degrees , 70.3% (26 of 37) of
      knees had a TTTG distance of more than 15 mm; at 30 degrees , only 24.3% (9 of
      37) exceeded this threshold. CONCLUSIONS: Knee flexion angle during imaging is a
      critical factor when measuring TTTG distance to evaluate patellofemoral
      instability. We found that the mean TTTG distance varied by 5.7 mm between 5
      degrees  and 30 degrees  of flexion in patients with symptomatic instability,
      although this relationship was not completely linear. Bisect offset and patellar
      tilt measurements mirrored this pattern, suggesting that TTTG distance influences
      patellar tracking in these patients. LEVEL OF EVIDENCE: Level IV, prognostic case
      series.

PMID- 25940400
TI  - Safety climate and the distracted driving experiences of truck drivers.
AB  - BACKGROUND: For truck drivers, distracted driving is a workplace behavior that
      increases occupational injury risk. We propose safety climate as an appropriate
      lens through which researchers can examine occupational distracted driving.
      METHODS: Using a mixed methods study design, we surveyed truck drivers using the
      Safety Climate Questionnaire (SCQ) complemented by semi-structured interviews of
      experts on distracted driving and truck safety. Safety climate was assessed by
      using the entire SCQ as an overall climate score, followed by factor analysis
      that identified the following safety climate factors: Communications and
      Procedures; Management Commitment; and Work Pressure. RESULTS: In multivariate
      regression, the overall safety climate scale was associated with having ever
      experienced a crash and/or distraction-involved swerving. Interview participants
      described how these SCQ constructs could affect occupational distracted driving.
      CONCLUSION: To reduce distraction-related crashes in their organizations,
      management can adhere to safe policies and procedures, invest in engineering
      controls, and develop safer communication procedures.

PMID- 25940398
TI  - Integration of PKPD relationships into benefit-risk analysis.
AB  - AIM: Despite the continuous endeavour to achieve high standards in medical care
      through effectiveness measures, a quantitative framework for the assessment of
      the benefit-risk balance of new medicines is lacking prior to regulatory
      approval. The aim of this short review is to summarise the approaches currently
      available for benefit-risk assessment. In addition, we propose the use of
      pharmacokinetic-pharmacodynamic (PKPD) modelling as the pharmacological basis for
      evidence synthesis and evaluation of novel therapeutic agents. METHODS: A
      comprehensive literature search has been performed using MESH terms in PubMed, in
      which articles describing benefit-risk assessment and modelling and simulation
      were identified. In parallel, a critical review of multi-criteria decision
      analysis (MCDA) is presented as a tool for characterising a drug's safety and
      efficacy profile. RESULTS: A definition of benefits and risks has been proposed
      by the European Medicines Agency (EMA), in which qualitative and quantitative
      elements are included. However, in spite of the value of MCDA as a quantitative
      method, decisions about benefit-risk balance continue to rely on subjective
      expert opinion. By contrast, a model-informed approach offers the opportunity for
      a more comprehensive evaluation of benefit-risk balance before extensive evidence
      is generated in clinical practice. CONCLUSIONS: Benefit-risk balance should be an
      integral part of the risk management plan and as such considered before marketing
      authorisation. Modelling and simulation can be incorporated into MCDA to support
      the evidence synthesis as well evidence generation taking into account the
      underlying correlations between favourable and unfavourable effects. In addition,
      it represents a valuable tool for the optimization of protocol design in
      effectiveness trials.

PMID- 25940401
TI  - Urinary, fecal, and dual incontinence in older U.S. Adults.
AB  - OBJECTIVES: To estimate the prevalence of urinary (UI), fecal (FI), and dual
      incontinence (DI) and to identify shared factors associated with each type of
      incontinence in older U.S. women and men. DESIGN: Population-based cross
      sectional study. SETTING: National Health and Nutrition Examination Survey
      (NHANES, 2005-2010). PARTICIPANTS: Women and men aged 50 and older. MEASUREMENTS:
      UI was defined as moderate to severe (>=3 on a validated UI severity index, range
      0-12); FI was at least monthly loss of solid, liquid, or mucus stool; and DI was
      the presence of UI and FI. RESULTS: Women were more likely than men to report UI
      only and DI but not FI only (UI only, women 19.8%, men 6.4%; FI only, women 8.2%,
      men 8.4%; DI women, 6.0%, men 1.9%). In both sexes, prevalence increased with
      age. In regression models adjusted for parity and hysterectomy, DI in women was
      associated with non-Hispanic white race (odds ratio (OR)=2.3, 95% confidence
      interval (CI)=1.5-3.4), depression (OR=4.7, 95% CI=2.0-11.1), comorbidities
      (OR=4.3, 95% CI=1.9-9.6 for >=3 comorbidities vs none), hysterectomy (OR=1.8, 95%
      CI=1.2-2.7), and diarrhea (OR=2.8, 95% CI=1.5-5.0). In men, ADL impairment
      (OR=2.4, 95% CI=1.2-4.9) and poorer self-rated health (OR=2.8, 95% CI=1.5-5.30)
      were associated with DI. CONCLUSION: UI, FI, and DI are common in older women and
      men. Factors associated with DI were distinct from those associated with UI and
      FI. There were also differences according to sex, with DI associated with
      depression and comorbid diseases in women and lack of functional ability and
      poorer self-rated health in men.

PMID- 25940397
TI  - TERT gene harbors multiple variants associated with pancreatic cancer
      susceptibility.
AB  - A small number of common susceptibility loci have been identified for pancreatic
      cancer, one of which is marked by rs401681 in the TERT-CLPTM1L gene region on
      chromosome 5p15.33. Because this region is characterized by low linkage
      disequilibrium, we sought to identify whether additional single nucleotide
      polymorphisms (SNPs) could be related to pancreatic cancer risk, independently of
      rs401681. We performed an in-depth analysis of genetic variability of the
      telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC)
      genes, in 5,550 subjects with pancreatic cancer and 7,585 controls from the
      PANcreatic Disease ReseArch (PANDoRA) and the PanScan consortia. We identified a
      significant association between a variant in TERT and pancreatic cancer risk
      (rs2853677, odds ratio = 0.85; 95% confidence interval = 0.80-0.90, p = 8.3 * 10(
      8)). Additional analysis adjusting rs2853677 for rs401681 indicated that the two
      SNPs are independently associated with pancreatic cancer risk, as suggested by
      the low linkage disequilibrium between them (r(2) = 0.07, D' = 0.28). Three
      additional SNPs in TERT reached statistical significance after correction for
      multiple testing: rs2736100 (p = 3.0 * 10(-5) ), rs4583925 (p = 4.0 * 10(-5) )
      and rs2735948 (p = 5.0 * 10(-5) ). In conclusion, we confirmed that the TERT
      locus is associated with pancreatic cancer risk, possibly through several
      independent variants.

PMID- 25940402
TI  - Carbohydrate-Based Nanocarriers Exhibiting Specific Cell Targeting with Minimum
      Influence from the Protein Corona.
AB  - Whenever nanoparticles encounter biological fluids like blood, proteins adsorb on
      their surface and form a so-called protein corona. Although its importance is
      widely accepted, information on the influence of surface functionalization of
      nanocarriers on the protein corona is still sparse, especially concerning how the
      functionalization of PEGylated nanocarriers with targeting agents will affect
      protein corona formation and how the protein corona may in turn influence the
      targeting effect. Herein, hydroxyethyl starch nanocarriers (HES-NCs) were
      prepared, PEGylated, and modified on the outer PEG layer with mannose to target
      dendritic cells (DCs). Their interaction with human plasma was then studied. Low
      overall protein adsorption with a distinct protein pattern and high specific
      affinity for DC binding were observed, thus indicating an efficient combination
      of "stealth" and targeting behavior. 

PMID- 25940404
TI  - Intramolecular Cooperative C-C Bond Cleavage Reaction of 1,3-Dicarbonyl Compounds
      with 2-Iodoanilines to Give o-(N-Acylamino)aryl Ketones and Multisubstituted
      Indoles.
AB  - A copper-catalyzed C-C bond cleavage reaction of 1,3-dicarbonyl compounds with 2
      iodoanilines was developed. In this process, the ortho effect played an important
      role in the reactivity and a new reaction pathway that involved a (2-aminophenyl)
      bis-(1,3-dicarbonyl) copper species was clearly observed by a time-course HRMS
      analysis of the reaction mixture. Unlike the previous reports, both the
      nucleophilic and electrophilic parts of the 1,3-dicarbonyl compound were coupled
      with 2-iodoaniline by C-C bond cleavage to form o-(N-acylamino)aryl ketones,
      which could be efficiently converted into multisubstituted indoles.

PMID- 25940406
TI  - Evaluation of the CAV1 gene in clinically, sonographically and histologically
      proven morphea patients.

PMID- 25940403
TI  - Unraveling the pathogenesis of Hoyeraal-Hreidarsson syndrome, a complex telomere
      biology disorder.
AB  - Hoyeraal-Hreidarsson (HH) syndrome is a multisystem genetic disorder
      characterized by very short telomeres and considered a clinically severe variant
      of dyskeratosis congenita. The main cause of mortality, usually in early
      childhood, is bone marrow failure. Mutations in several telomere biology genes
      have been reported to cause HH in about 60% of the HH patients, but the genetic
      defects in the rest of the patients are still unknown. Understanding the
      aetiology of HH and its diverse manifestations is challenging because of the
      complexity of telomere biology and the multiple telomeric and non-telomeric
      functions played by telomere-associated proteins in processes such as telomere
      replication, telomere protection, DNA damage response and ribosome and
      spliceosome assembly. Here we review the known clinical complications, molecular
      defects and germline mutations associated with HH, and elucidate possible
      mechanistic explanations and remaining questions in our understanding of the
      disease. 

PMID- 25940408
TI  - NHLBI state of the science symposium in therapeutic apheresis: Knowledge gaps and
      research opportunities in the area of hematology-oncology.
AB  - The National Heart Lung and Blood Institute (NHLBI) hosted a two-day state of the
      science symposium on therapeutic apheresis in Bethesda, MD on November 28th-29th,
      2012. The purpose of the symposium was multifaceted, and included the following
      aims: (a) To discuss this state of research and key scientific questions in
      apheresis medicine; (b) To identify gaps in knowledge for relevant cardiovascular
      diseases, hematological and oncological diseases, infectious diseases and sepsis,
      renal diseases, and neurological diseases where there may be strong therapeutic
      rationale for the application of apheresis treatments; (c) To explore ways of
      coordinating therapeutic apheresis with other medical disciplines and treatment
      modalities; (d) To identify and prioritize the most important research questions
      to be answered in apheresis medicine; and (e) To offer NHLBI suggestions on how a
      structured research approach can be applied to the therapeutic apheresis research
      agenda in future years. The following document summarizes three such key
      proposals presented at the meeting for evaluating apheresis therapy for the
      treatment of pain in sickle cell disease, heparin induced thrombocytopenia, and
      leukostasis from acute myeloid leukemia. The challenges and limitations regarding
      apheresis therapy for each disease are discussed, and avenues for future
      investigation for each disease are outlined.

PMID- 25940407
TI  - Variation in ectomycorrhizal fungal communities associated with Oreomunnea
      mexicana (Juglandaceae) in a Neotropical montane forest.
AB  - Neotropical montane forests are often dominated by ectomycorrhizal (EM) tree
      species, yet the diversity of their EM fungal communities remains poorly
      explored. In lower montane forests in western Panama, the EM tree species
      Oreomunnea mexicana (Juglandaceae) forms locally dense populations in forest
      otherwise characterized by trees that form arbuscular mycorrhizal (AM)
      associations. The objective of this study was to compare the composition of EM
      fungal communities associated with Oreomunnea adults, saplings, and seedlings
      across sites differing in soil fertility and the amount and seasonality of
      rainfall. Analysis of fungal nrITS DNA (nuclear ribosomal internal transcribed
      spacers) revealed 115 EM fungi taxa from 234 EM root tips collected from adults,
      saplings, and seedlings in four sites. EM fungal communities were equally species
      rich and diverse across Oreomunnea developmental stages and sites, regardless of
      soil conditions or rainfall patterns. However, ordination analysis revealed high
      compositional turnover between low and high fertility/rainfall sites located ca.
      6 km apart. The EM fungal community was dominated by Russula (ca. 36 taxa).
      Cortinarius, represented by 14 species and previously reported to extract
      nitrogen from organic sources under low nitrogen availability, was found only in
      low fertility/high rainfall sites. Phylogenetic diversity analyses of Russula
      revealed greater evolutionary distance among taxa found on sites with contrasting
      fertility and rainfall than was expected by chance, suggesting that environmental
      differences among sites may be important in structuring EM fungal communities.
      More research is needed to evaluate whether EM fungal taxa associated with
      Oreomunnea form mycorrhizal networks that might account for local dominance of
      this tree species in otherwise diverse forest communities. 

PMID- 25940409
TI  - Introduction of universal prestorage leukodepletion of blood components, and
      outcomes in transfused cardiac surgery patients.
AB  - OBJECTIVE: To assess whether introduction of universal leukodepletion (ULD) of
      red blood cells (RBCs) for transfusion was associated with improvements in
      cardiac surgery patient outcomes. METHODS: Retrospective study (2005-2010)
      conducted at 6 institutions. Associations between leukodepletion and outcomes of
      mortality, infection, and acute kidney injury (AKI) were modeled by logistic
      regression, and intensive care unit length of stay (LOS) in survivors was
      explored using linear regression. To examine trends over time, odds ratios (ORs)
      for outcomes of transfused were compared with nontransfused patients, including a
      comparison with nontransfused patients who were selected based on propensity
      score for RBC transfusion. RESULTS: We studied 14,980 patients, of whom 8857
      (59%) had surgery pre-ULD. Transfusions of RBCs were made in 3799 (43%) pre-ULD,
      and 2525 (41%) post-ULD. Administration of exclusively leukodepleted, versus
      exclusively nonleukodepleted, RBCs was associated with lower incidence of AKI
      (adjusted OR 0.80, 95% confidence interval [CI] 0.65-0.98, P = .035), but no
      difference in mortality or infection. For post-ULD patients, no difference was
      found in mortality (OR 0.96, 95% CI 0.76-1.22, P = .76) or infection (OR 0.91,
      95% CI 0.79-1.03, P = .161); however, AKI was reduced (OR 0.79 95% CI 0.68-0.92,
      P = .003). However, ORs for post-ULD outcomes were not significantly different in
      nontransfused, versus transfused, patients. Furthermore, those who received
      exclusively nonleukodepleted RBCs were more likely to have surgery post-ULD.
      CONCLUSIONS: Universal leukodepletion was not associated with reduced mortality
      or infection in transfused cardiac surgery patients. An association was found
      between ULD and reduced AKI; however, this reduction was not significantly
      different from that seen in nontransfused patients, and other changes in care
      most likely explain such changes in renal outcomes.

PMID- 25940410
TI  - Total endovascular repair for acute type B dissection in the setting of right
      aortic arch with aberrant left subclavian artery and Kommerell diverticulum.

PMID- 25940411
TI  - The potential predictive risk of not measuring a potential predictor of risk.

PMID- 25940412
TI  - Bloody white cells-no problem: Let's solve hemorrhage out of the operating room.

PMID- 25940413
TI  - Stenting of an outflow graft obstruction after implantation of a continuous-flow,
      axial-flow left ventricular assist device.

PMID- 25940414
TI  - Septal myectomy after failed alcohol ablation: Does previous percutaneous
      intervention compromise outcomes of myectomy?
AB  - OBJECTIVE: The impact of prior alcohol septal ablation in patients who require
      septal myectomy for hypertrophic obstructive cardiomyopathy is unknown. METHODS:
      Thirty-one patients with unsuccessful alcohol septal ablation who underwent
      septal myectomy were matched 1:2 to patients having had a myectomy as the only
      invasive procedure for hypertrophic obstructive cardiomyopathy. Study outcomes
      were cardiac death, advanced heart failure, and appropriate implantable
      cardioverter defibrillator discharge. The results of surgery, echocardiograms,
      and pathology specimens were compared between groups. RESULTS: Patients with
      previous alcohol septal ablation had increased diastolic dysfunction in
      preoperative echocardiography, as well as more implantable cardioverter
      defibrillators implanted (32% vs 11%, P = .01), more arrhythmias in preoperative
      Holter monitoring (43% vs 13%, P = .02), and a higher incidence of postoperative
      complete heart block (19.4% vs 1.6%, P < .01). Two patients died early
      postoperatively in the prior alcohol septal ablation group, and no patients died
      in the primary myectomy group. One patient in each group had an implantable
      cardioverter defibrillator (P = .52). At a mean follow-up of 3.2 years, 7 of 31
      patients and 6 of 62 patients progressed to advanced heart failure in the prior
      alcohol septal ablation group and the primary myectomy group, respectively (P =
      .1) Histopathologic analysis demonstrated greater interstitial (70% vs 26%, P <
      .01) and endocardial fibrosis (87% vs 67%, P = .04) in the alcohol septal
      ablation group. CONCLUSIONS: Patients with prior alcohol septal ablation
      undergoing surgical septal myectomy may have an increased risk of cardiac death,
      advanced heart failure, and implantable cardioverter defibrillator discharges.
      This supports septal myectomy as the preferred treatment for septal reduction
      therapy, avoiding scarring and diastolic dysfunction inherent to alcohol septal
      ablation.

PMID- 25940415
TI  - Five-year results of the pilot trial of a sutureless valve.
AB  - OBJECTIVE: A prospective trial was designed to evaluate the feasibility of the
      Perceval sutureless aortic valve. We report the 5-year clinical and hemodynamic
      outcome. METHODS: A total of 30 patients (mean age: 80.4 +/- 3.8 years; mean
      logistic European System for Cardiac Operative Risk Evaluation [euroSCORE]: 13.2
      +/- 7.3) received the valve in 3 European centers, between April 2007 and
      February 2008. Cumulative follow-up was 92.67 patient-years, with a median of 4.2
      years. Patients with a small annulus were selected because only sizes 21 and 23
      mm (covering annuli diameters from 19 to 23 mm) were available at this early
      stage of the trial. In 37% of the patients, a 21-mm valve was used; 63% received
      a 23-mm valve; 14 patients had concomitant coronary artery bypass grafting.
      Clinical and hemodynamic follow-up evaluation were performed annually, including
      echocardiography. RESULTS: Procedural success was 100%. Cardiopulmonary bypass
      time and cross-clamp time in isolated aortic valve replacement were 46.4 +/- 6.7
      minutes and 29.3 +/- 8.0 minutes, respectively. One patient died during the
      hospital stay. Postoperative complications included 1 patient with mediastinal
      bleeding, and 1 with atrioventricular block that led to pacemaker implantation.
      No stroke occurred in either the early or late period. At the last available
      follow-up, 22 patients were alive. The mean gradient was 9.3 mm Hg, with an
      effective orifice area of 1.7 cm(2) at 5 years. No dislodgement, structural valve
      deterioration, hemolysis, or valve thrombosis was reported. CONCLUSIONS: This
      study reports the first and longest experience with a truly sutureless valve,
      evaluating implantation feasibility and valve safety. Results from up to 5 years
      of follow up confirmed the performance and safety of this device, even in a
      medium- to high-risk patient population with a small aortic annulus.

PMID- 25940416
TI  - Aortic dissection with acute malperfusion syndrome: Endovascular fenestration via
      the funnel technique.
AB  - OBJECTIVE: To analyze the short- and long-term results of an original aortic
      fenestration method using the funnel technique during aortic dissection
      complicated by malperfusion syndrome. METHODS: The funnel technique consists of
      deployment of an uncovered aortic stent graft placed from the false to the right
      lumen through an intimal flap aortic fenestration made by balloon angioplasty.
      Twenty-eight patients presenting with an aortic dissection (type A, n = 19; type
      B, n = 9) were treated for malperfusion syndrome owing to dynamic compression (16
      renal, 17 bowel, and 13 lower limb ischemia) using the aforementioned technique,
      and had follow-up evaluation at short term (30 days) and long term (mean: 55 +/-
      40 months). Eight patients had severe ischemia on arrival (6 bowel, 7 renal, 3
      lower limb). RESULTS: Technical success was achieved in 27 of 28 patients (96%),
      and ischemic symptoms had disappeared in 25 of 28 patients (89%) at short-term
      follow up. Five patients presented postprocedure complications: 4 minor and 1
      major with arterial thrombosis which caused technical failure (3.6%). The 30-day
      mortality rate was 7% (n = 2), related to bowel ischemia complications. At long
      term follow up, 21 patients had a stable thoracic aortic diameter (91%).
      CONCLUSIONS: The funnel technique, in cases of malperfusion syndrome after aortic
      dissection, safely improves short- and long-term clinical outcome, and could
      represent an interesting alternative in the management of patients. The
      hemodynamic efficiency of this technique may account for a lower mortality in our
      series.

PMID- 25940417
TI  - Sequential and timely transfection of hepatocyte growth factor and monocyte
      chemotactic protein-1 ameliorates hyperkinetic pulmonary artery hypertension in
      rabbits.
AB  - OBJECTIVE: To investigate the effect of sequential and timely transfection of the
      recombinant human hepatocyte growth factor (hHGF) gene and human monocyte
      chemotactic protein-1 (hMCP-1) gene on hyperkinetic pulmonary artery hypertension
      in a rabbit model. METHODS: The rabbits with pulmonary artery hypertension were
      randomly separated into 5 groups: control; hHGF; hMCP-1; hHGF/hMCP-1 simultaneous
      transfection; and hHGF/hMCP-1 sequential, timely transfection. Two weeks after
      the transfection, real-time polymerase chain reaction and immunohistochemistry
      examination were used to detect the expression of hHGF and hMCP-1. Four weeks
      later, the hemodynamic parameters were measured, and immunohistochemical and
      immunofluorescence staining were performed, to investigate microvascular density
      and arterialization. RESULTS: The final adenovirus coding with enhanced green
      fluorescent protein-hMCP-1 virus was 3 * 10(10) plaque-forming units/mL, and the
      purity of adenovirus coding with hHGF was 1.31. Three days after the
      transfection, enhance green fluorescent protein hMCP-1 green fluorescence was
      detected in the lung tissues and increased to its peak point in 1 week. Two weeks
      later, hHGF and hMCP-1 were expressed in all transfection groups. By the end of 4
      weeks, the mean pulmonary artery pressure in the hHGF/hMCP-1 sequential and
      timely transfection group was lower than that in the other groups. Confirmed by
      immunohistochemical and immunofluorescence staining, the microvascular and
      arteriolar density in the lung tissues of the sequential and timely hHGF/hMCP-1
      transfection group were higher than that in the other groups. CONCLUSIONS:
      Expression of hHGF and hMCP-1 were found in rabbit lung after gene transfection
      via an airway approach. By increasing the pulmonary microvascular density and
      promoting arterializations, sequential and timely hHGF/hMCP-1 transfection
      ameliorates the shunt flow-induced pulmonary artery hypertension.

PMID- 25940419
TI  - Useful surgical instruments for the resection of subaortic stenosis.

PMID- 25940418
TI  - Quantifying "normalized" regional left ventricular contractile function in
      ischemic coronary artery disease.
AB  - OBJECTIVE: When significant coronary lesions are identified by angiography,
      regional left ventricular (LV) contractile function often plays a role in
      determining candidacy for revascularization. To improve on current subjective and
      nonquantitative metrics of regional LV function, we tested a z-score
      "normalization" of regional strain information quantified from clinically
      acquired high-resolution LV geometric datasets. METHODS: Test subjects (n = 120)
      underwent cardiac MRI with multiple 3-dimensional strain parameters calculated
      from tissue tag-plane displacement data. Sixty healthy volunteers contributed
      strain parameter data at each of 15,300 LV grid points, to form a normal human
      strain database. Point-specific database comparisons were made in 60 patients who
      had documented coronary artery disease (CAD), by angiography. Patient-specific,
      color-coded 3-dimensional LV maps of z-score-normalized contractile function were
      generated. RESULTS: Blinded clinical review indicated that 55% (33 of 60) of the
      patients with CAD had significant regional contractile abnormalities by 1 of 3
      "gold-standard" criteria: (1) Q waves on electrocardiography (ECG); (2) infarct
      on radionuclide single-photon emission computed tomography (SPECT); or (3)
      akinesia or dyskinesia on echocardiography. Consistency among all gold-standard
      metrics was found for only 19% (6 of 31) of patients with CAD who had >=2
      available metrics. Blinded MRI-based, multiparametric, strain z-score
      localization of contractile abnormalities was accurate in 89% (ECG), 97% (SPECT),
      and 95% (echocardiography). CONCLUSIONS: Nonsubjective normalization of regional
      LV contractile function by z-score calculation from a normal human strain
      database can localize and quantitatively display regional wall motion
      abnormalities in patients with CAD. This high-resolution localization of regional
      wall motion abnormalities may help improve the accuracy of therapeutic
      intervention in patients who have CAD.

PMID- 25940420
TI  - Revisiting the brachiofemoral through-and-through wire technique for hybrid arch
      repair with a problematic elephant trunk.

PMID- 25940421
TI  - Uniportal bilateral video-assisted thoracoscopic extended thymectomy for
      myasthenia gravis: A case report.

PMID- 25940422
TI  - Alternate models for optimal cardiovascular and thoracic critical care from a
      resident's perspective.

PMID- 25940423
TI  - Crane technique with the vacuum bell device for improving access in the Nuss
      procedure.

PMID- 25940424
TI  - Retinoblastoma: diagnosis and management--the UK perspective.
AB  - In the developed world, retinoblastoma is an uncommon yet highly curable ocular
      malignancy of childhood affecting 40-50 children in the UK each year. The
      presenting signs, most commonly leukocoria and squint, should alert the primary
      care physician or secondary care physician to examine for the red reflex, the
      absence of which is an indication for urgent ophthalmology assessment. Diagnosis
      is made by clinical examination and staging may include bone marrow sampling,
      lumbar puncture and MRI scanning. CT should be avoided to reduce radiation
      exposure in a population of whom a proportion are at considerable risk of second
      malignancies. Although enucleation is necessary for many children, over recent
      years there has been a growing emphasis on conservative management in an attempt
      to reduce the need for enucleation and avoid the adverse late effects associated
      with external beam radiotherapy. This review will describe approaches to
      treatment in the UK and how the stage, laterality and position of the tumour
      within the eye influence treatment choices. 

PMID- 25940425
TI  - Conflict escalation in paediatric services: findings from a qualitative study.
AB  - OBJECTIVE: To explore clinician and family experiences of conflict in paediatric
      services, in order to map the trajectory of conflict escalation. DESIGN:
      Qualitative interview study, employing extreme-case sampling. Interviews were
      analysed using an iterative thematic approach to identify common themes regarding
      the experience and escalation of conflict. PARTICIPANTS: Thirty-eight health
      professionals and eight parents. All participants had direct experience of
      conflict, including physical assault and court proceedings, at the interface of
      acute and palliative care. SETTING: Two teaching hospitals, one district general
      hospital and two paediatric hospices in England, in 2011. RESULTS: Conflicts
      escalate in a predictable manner. Clearly identifiable behaviours by both
      clinicians and parents are defined as mild, moderate and severe. Mild describes
      features like the insensitive use of language and a history of unresolved
      conflict. Moderate involves a deterioration of trust, and a breakdown of
      communication and relationships. Severe marks disintegration of working
      relationships, characterised by behavioural changes including aggression, and a
      shift in focus from the child's best interests to the conflict itself. Though
      conflicts may remain at one level, those which escalated tended to move
      sequentially from one level to the next. CONCLUSIONS: Understanding how conflicts
      escalate provides clinicians with a practical, evidence-based framework to
      identify the warning signs of conflict in paediatrics.

PMID- 25940426
TI  - Influence of water and fat heterogeneity on fat-referenced MR thermometry.
AB  - PURPOSE: To investigate the effect of the aqueous and fatty tissue magnetic
      susceptibility distribution on absolute and relative temperature measurements as
      obtained directly from the water/fat (w/f) frequency difference. METHODS:
      Absolute thermometry was investigated using spherical phantoms filled with pork
      and margarine, which were scanned in three orthogonal orientations. To evaluate
      relative fat referencing, multigradient echo scans were acquired before and after
      heating pork tissue via high-intensity focused ultrasound (HIFU). Simulations
      were performed to estimate the errors that can be expected in human breast
      tissue. RESULTS: The sphere experiment showed susceptibility-related errors of
      8.4  degrees C and 0.2  degrees C for pork and margarine, respectively. For
      relative fat referencing measurements, fat showed pronounced phase changes of
      opposite polarity to aqueous tissue. The apparent mean temperature for a
      numerical breast model assumed to be 37  degrees C was 47.2 +/- 21.6  degrees C.
      Simulations of relative fat referencing for a HIFU sonication (DeltaT = 29.7 
      degrees C) yielded a maximum temperature error of 6.6  degrees C compared with
      2.5  degrees C without fat referencing. CONCLUSION: Variations in the observed
      frequency difference between water and fat are largely due to variations in the
      w/f spatial distribution. This effect may lead to considerable errors in absolute
      MR thermometry. Additionally, fat referencing may exacerbate rather than correct
      for proton resonance frequency shift-temperature measurement errors.

PMID- 25940427
TI  - Clinical outcome of recurrent locally advanced cervical cancer (LACC) submitted
      to primary multimodality therapies.
AB  - OBJECTIVES: Recurrence of disease represents a clinical challenge in cervical
      cancer patients, especially when all available treatment modalities have been
      used in the primary setting. The aim of this study was to analyze the patterns of
      recurrence and their association with clinical outcome in locally advanced
      cervical cancer (LACC) patients submitted to primary chemoradiation (CTRT)
      followed by radical surgery (RS). METHODS: This study was conducted on 364 LACC
      patients treated with CTRT plus RS since January 1996 to July 2012. For each
      relapse, information on date of clinical/pathological recurrence, and pattern of
      disease presentation were retrieved. Post-relapse survival (PRS) was recorded
      from the date of recurrence to the date of death for disease or last seen.
      Survival probabilities were compared by the log rank test. Cox's regression model
      with stepwise variable selection was used for multivariate prognostic analysis
      for PRS. RESULTS: Within a median follow-up of 42months, 75 recurrences (20.6%)
      and 54 disease-associated deaths (14.8%) were recorded. By analysing the pattern
      of relapse, most of the recurrences were outside the irradiated field (n=43,
      57.3%) and the most frequently observed site was visceral (n=16, 21.3%). Among
      the parameters of the recurrence associated with PRS including the pattern of
      recurrence, the size of recurrence, SCC-Ag serum levels at recurrence, and
      secondary radical surgery, only the last one retained an independent predictive
      role in reducing the risk of death (p=0.037). CONCLUSIONS: The feasibility of
      secondary radical resection positively impacts on PRS of LACC patients submitted
      to multimodality primary treatments.

PMID- 25940429
TI  - Bronchoscopic procedures and lung biopsies in pediatric lung transplant
      recipients.
AB  - Bronchoscopy remains a pivotal diagnostic and therapeutic intervention in
      pediatric patients undergoing lung transplantation (LTx). Whether performed as
      part of a surveillance protocol or if clinically indicated, fibre-optic
      bronchoscopy allows direct visualization of the transplanted allograft, and in
      particular, an assessment of the patency of the bronchial anastomosis (or
      tracheal anastomosis following heart-lung transplantation). Additionally,
      bronchoscopy facilitates differentiation of infective processes from rejection
      episodes through collection and subsequent assessment of bronchoalveolar lavage
      (BAL) and transbronchial biopsy (TBBx) samples. Indeed, the diagnostic criteria
      for the grading of acute cellular rejection is dependent upon the
      histopathological assessment of biopsy samples collected at the time of
      bronchoscopy. Typically, performed in an out-patient setting, bronchoscopy is
      generally a safe procedure, although complications related to hemorrhage and
      pneumothorax are occasionally seen. Airway complications, including stenosis,
      malacia, and dehiscence are diagnosed at bronchoscopy, and subsequent management
      including balloon dilatation, laser therapy and stent insertion can also be
      performed bronchoscopically. Finally, bronchoscopy has been and continues to be
      an important research tool allowing a better understanding of the immuno-biology
      of the lung allograft through the collection and analysis of collected BAL and
      TBBx samples. Whilst new investigational tools continue to evolve, the simple
      visualization and collection of samples within the lung allograft by bronchoscopy
      remains the gold standard in the evaluation of the lung allograft. This review
      describes the use and experience of bronchoscopy following lung transplantation
      in the pediatric setting.

PMID- 25940430
TI  - Toona Sinensis ameliorates insulin resistance via AMPK and PPARgamma pathways.
AB  - Toona Sinensis leaf (TSL) extract with a beneficial effect for managing
      hyperglycemia has been reported, however the underlying mechanism by which TSL
      extract acts as an insulin sensitizer remains uncertain, especially in peripheral
      tissues. TSL 95% ethanol extract exhibited the highest transactivity of PPARgamma
      and contained the highest amounts of natural PPARgamma ligands including palmitic
      acid, linoleic acid, and alpha-linolenic acid among different TSL ethanol
      extracts (0, 10, 50, 70, and 95%). The efficacy and the mechanism of TSL ethanol
      extract (95%) mediated anti-diabetic effects were examined by both in vivo and in
      vitro models in this study. An improved whole-body insulin sensitivity was
      observed in high-fat diet-fed (HFD) mice after 14 weeks of TSL treatment, as
      evidenced by a faster rate of plasma glucose clearing. The improved insulin
      sensitivity was through direct stimulation of PPARgamma and adiponectin
      expression in adipose tissues of HFD mice. In addition to the PPARgamma pathway,
      TSL stimulated glucose uptake via directly inducing AMPKalpha but not AS160
      activation in C2C12 myotubes under palmitate-induced insulin resistance. TSL
      successfully induced sirtuin 1 and restored PGC1alpha, but failed to restore
      mitochondrial electron transport complexes I, III, IV and V in mRNA levels. Loss
      of the mitochondrial membrane potential coupled with AMPK activation suggests
      that TSL acts as a mitochondrial inhibitor to stimulate AMPK-mediated glucose
      uptake. This study demonstrated that TSL stimulated glucose uptake via AMPK
      activation in skeletal muscles and promoted PPARgamma and normalized adiponectin
      expression in adipose tissues, thereby ameliorating insulin resistance.

PMID- 25940432
TI  - Toward a new paradigm of knee osteoarthritis.

PMID- 25940433
TI  - Umbolith: a cause of umbilical discharge and omphalitis.

PMID- 25940434
TI  - Chlamydia trachomatis genotypes in school adolescents, Italy.
AB  - Chlamydia trachomatis genogroups using ompA and multilocus sequence typing (MLST)
      were determined in consecutive isolates from school students aged 18 or older in
      the district of Brescia, Italy, 2012-2013. Among 40 samples, 4 ompA genovars and
      18 STs were identified. Genovar E predominated (70 %) including five STs derived
      from ST59 (29 % of all isolates). This study, combining ompA and MLST typing of
      C. trachomatis school teenagers, suggests limited mixing and sexual interchange
      in this population.

PMID- 25940435
TI  - Seroprevalence and risk factors of hepatitis E virus infection among children in
      China.
AB  - Hepatitis E virus (HEV) infection is an important public health concern
      worldwide, especially in developing countries, causing waterborne outbreaks as
      well as sporadic autochthonous hepatitis. China is usually considered to be a HEV
      endemic area, but the prevalence of HEV infection in children in mainland China
      remains unclear. Between May 2013 and July 2014, a cross-sectional study was
      conducted to estimate the seroprevalence and potential risk factors associated
      with the acquisition of HEV infection by children in China. A total of 1,500
      healthy children (range 1-18; 942 and 558 from urban and rural areas,
      respectively) were recruited to examine for the presence of anti-HEV IgG and IgM
      antibodies by enzyme-linked immunosorbent assay. Socio-demographic and behavioral
      characteristics from the examined children were obtained. The overall
      seroprevalence of HEV in the examined children was 14.93%. Of these, 174 (11.60%)
      were positive for only anti-HEV IgG antibodies, 50 (3.33%) were IgM positive and
      IgG negative, and 44 (2.93%) were positive for both anti-HEV IgG and IgM
      antibodies. Age, type of residence area, contact with pigs, and source of
      drinking water were found to be associated with HEV infection. These findings
      demonstrated the high prevalence of HEV and the considerable potential for the
      transmission of HEV infection in children in China.

PMID- 25940436
TI  - From the Editor's Desk.

PMID- 25940437
TI  - From the core to beyond the margin: a genomic picture of glioblastoma intratumor
      heterogeneity.
AB  - Glioblastoma (GB) is a highly invasive primary brain tumor that almost
      systematically recurs despite aggressive therapies. One of the most challenging
      problems in therapy of GB is its extremely complex and heterogeneous molecular
      biology. To explore this heterogeneity, we performed a genome-wide integrative
      screening of three molecular levels: genome, transcriptome, and methylome. We
      analyzed tumor biopsies obtained by neuro-navigation in four distinct areas for
      10 GB patients (necrotic zone, tumor zone, interface, and peripheral brain zone).
      We classified samples and deciphered a key genes signature of intratumor
      heterogeneity by Principal Component Analysis and Weighted Gene Co-expression
      Network Analysis. At the genome level, we identified common GB copy number
      alterations and but a strong interindividual molecular heterogeneity.
      Transcriptome analysis highlighted a pronounced intratumor architecture
      reflecting the surgical sampling plan of the study and identified gene modules
      associated with hallmarks of cancer. We provide a signature of key cancer
      heterogeneity genes highly associated with the intratumor spatial gradient and
      show that it is enriched in genes with correlation between methylation and
      expression levels. Our study confirms that GBs are molecularly highly diverse and
      that a single tumor can harbor different transcriptional GB subtypes depending on
      its spatial architecture. 

PMID- 25940438
TI  - Tudor staphylococcal nuclease drives chemoresistance of non-small cell lung
      carcinoma cells by regulating S100A11.
AB  - Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small
      cell lung cancer (NSCLC), the major lung cancer subtype, is characterized by high
      resistance to chemotherapy. Here we demonstrate that Tudor staphylococcal
      nuclease (SND1 or TSN) is overexpressed in NSCLC cell lines and tissues, and is
      important for maintaining NSCLC chemoresistance. Downregulation of TSN by RNAi in
      NSCLC cells led to strong potentiation of cell death in response to cisplatin.
      Silencing of TSN was accompanied by a significant decrease in S100A11 expression
      at both mRNA and protein level. Downregulation of S100A11 by RNAi resulted in
      enhanced sensitivity of NSCLC cells to cisplatin, oxaliplatin and 5-fluouracil.
      AACOCF(3), a phospholipase A(2) (PLA(2)) inhibitor, strongly abrogated
      chemosensitization upon silencing of S100A11 suggesting that PLA(2) inhibition by
      S100A11 governs the chemoresistance of NSCLC. Moreover, silencing of S100A11
      stimulated mitochondrial superoxide production, which was decreased by AACOCF(3),
      as well as N-acetyl-L-cysteine, which also mimicked the effect of PLA(2)
      inhibitor on NSCLC chemosensitization upon S100A11 silencing. Thus, we present
      the novel TSN-S100A11-PLA(2) axis regulating superoxide-dependent apoptosis,
      triggered by platinum-based chemotherapeutic agents in NSCLC that may be targeted
      by innovative cancer therapies.

PMID- 25940439
TI  - Infiltrated pre-adipocytes increase prostate cancer metastasis via modulation of
      the miR-301a/androgen receptor (AR)/TGF-beta1/Smad/MMP9 signals.
AB  - High fat dietary intake may increase the risk of prostate cancer (PCa). Pre
      adipocytes, one of the basic components in the tumor microenvironment (TME), are
      capable of differentiating into adipose tissues and play key roles to affect PCa
      progression. Here we found the pre-adipocytes could be recruited more easily to
      PCa than its surrounding normal prostate tissue. In vitro co-culture system also
      confirmed PCa has a better capacity than normal prostate to recruit pre
      adipocytes. The consequences of recruiting more pre-adipocytes may then increase
      PCa cell invasion. Mechanism dissection revealed infiltrating pre-adipocytes
      might function through down-regulation of the androgen receptor (AR) via
      modulation of miR-301a, and then increase PCa cell invasion via induction of TGF
      beta1/Smad/MMP9 signals. The mouse model with orthotopically xenografted PCa
      CWR22Rv1 cells with pre-adipocytes also confirmed that infiltrating pre
      adipocytes could increase PCa cell invasion via suppressing AR signaling.
      Together, our results reveal a new mechanism showing pre-adipocytes in the
      prostate TME can be recruited to PCa to increase PCa metastasis via modulation of
      the miR-301a/AR/TGF-beta1/Smad/MMP9 signals. Targeting this newly identified
      signaling may help us to better inhibit PCa metastasis. 

PMID- 25940440
TI  - ERp19 contributes to tumorigenicity in human gastric cancer by  promoting cell
      growth, migration and invasion.
AB  - ERp19, a mammalian thioredoxin-like protein, plays a key role in defense against
      endoplasmic reticulum stress. It belongs to the protein disulfide isomerize (PDI)
      family, whose members have been implicated in development of breast, ovarian and
      gastrointestinal cancers. However, the role of ERp19 in gastric cancer (GC)
      remains undefined. Therefore, we sought to investigate the expression and
      prognostic value of ERp19 in GC patients, and to explore the role of ERp19 in
      tumorigenicity. Expression of ERp19 in gastric tissues was assessed by
      immunohistochemical staining and real-time PCR in clinical samples of GC
      patients. Statistical analysis of clinical cases revealed that the expression
      levels of ERp19 were higher in tumor tissues than non-tumor tissues. And the
      level of ERp19 expression was correlated with tumor size, lymph node involvement
      and poor clinical prognosis. Furthermore, ERp19 knockdown dramatically suppressed
      gastric cancer cell growth, inhibited cellular migration/invasion and down
      regulated the phosphorylation of FAK and paxillin, whereas ERp19 over-expression
      reversed these changes. We conclude that ERp19 contributes to tumorigenicity and
      metastasis of GC by activating the FAK signaling pathway, and may function as an
      oncogene in GC. ERp19 may represent a new diagnostic and prognostic marker and a
      novel target for the treatment of GC.

PMID- 25940441
TI  - Tumor suppressive microRNA-137 negatively regulates Musashi-1 and colorectal
      cancer progression.
AB  - Stem cell marker, Musashi-1 (MSI1) is over-expressed in many cancer types;
      however the molecular mechanisms involved in MSI1 over-expression are not well
      understood. We investigated the microRNA (miRNA) regulation of MSI1 and the
      implications this regulation plays in colorectal cancer. MicroRNA miR-137 was
      identified as a MSI1-targeting microRNA by immunoblotting and luciferase reporter
      assays. MSI1 protein was found to be highly expressed in 79% of primary rectal
      tumors (n=146), while miR-137 expression was decreased in 84% of the rectal tumor
      tissues (n=68) compared to paired normal mucosal samples. In addition to reduced
      MSI1 protein, exogenous expression of miR-137 inhibited cell growth, colony
      formation, and tumorsphere growth of colon cancer cells. Finally, in vivo studies
      demonstrated that induction of miR-137 can decrease growth of human colon cancer
      xenografts. Our results demonstrate that miR-137 acts as a tumor-suppressive
      miRNA in colorectal cancers and negatively regulates oncogenic MSI1. 

PMID- 25940442
TI  - [Atrial appendage occlusion in atrial fibrillation? Pro].

PMID- 25940428
TI  - No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer.
AB  - OBJECTIVE: Clinical genetic testing is commercially available for rs61764370, an
      inherited variant residing in a KRAS 3' UTR microRNA binding site, based on
      suggested associations with increased ovarian and breast cancer risk as well as
      with survival time. However, prior studies, emphasizing particular subgroups,
      were relatively small. Therefore, we comprehensively evaluated ovarian and breast
      cancer risks as well as clinical outcome associated with rs61764370. METHODS:
      Centralized genotyping and analysis were performed for 140,012 women enrolled in
      the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816
      controls), the Breast Cancer Association Consortium (33,530 breast cancer
      patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2
      (14,765 BRCA1 and 7904 BRCA2 mutation carriers). RESULTS: We found no association
      with risk of ovarian cancer (OR=0.99, 95% CI 0.94-1.04, p=0.74) or breast cancer
      (OR=0.98, 95% CI 0.94-1.01, p=0.19) and results were consistent among mutation
      carriers (BRCA1, ovarian cancer HR=1.09, 95% CI 0.97-1.23, p=0.14, breast cancer
      HR=1.04, 95% CI 0.97-1.12, p=0.27; BRCA2, ovarian cancer HR=0.89, 95% CI 0.71
      1.13, p=0.34, breast cancer HR=1.06, 95% CI 0.94-1.19, p=0.35). Null results were
      also obtained for associations with overall survival following ovarian cancer
      (HR=0.94, 95% CI 0.83-1.07, p=0.38), breast cancer (HR=0.96, 95% CI 0.87-1.06,
      p=0.38), and all other previously-reported associations. CONCLUSIONS: rs61764370
      is not associated with risk of ovarian or breast cancer nor with clinical outcome
      for patients with these cancers. Therefore, genotyping this variant has no
      clinical utility related to the prediction or management of these cancers.

PMID- 25940444
TI  - Influenza vaccines for preventing cardiovascular disease.
AB  - BACKGROUND: This is an update of the original review published in 2008. The risk
      of adverse cardiovascular outcomes is increased with influenza-like infection,
      and vaccination against influenza may improve cardiovascular outcomes.
      OBJECTIVES: To assess the potential benefits of influenza vaccination for primary
      and secondary prevention of cardiovascular disease. SEARCH METHODS: We searched
      the following electronic databases on 18 October 2013: The Cochrane Library
      (including Cochrane Central Register of Controlled Trials (CENTRAL), Database of
      Abstracts of Reviews of Effects (DARE), Economic Evaluation Database (EED) and
      Health Technology Assessment database (HTA)), MEDLINE, EMBASE, Science Citation
      Index Expanded, Conference Proceedings Citation Index - Science and ongoing
      trials registers (www.controlled-trials.com/ and www.clinicaltrials.gov). We
      examined reference lists of relevant primary studies and systematic reviews. We
      performed a limited PubMed search on 20 February 2015, just before publication.
      SELECTION CRITERIA: Randomised controlled trials (RCTs) of influenza vaccination
      compared with placebo or no treatment in participants with or without
      cardiovascular disease, assessing cardiovascular death or non-fatal
      cardiovascular events. DATA COLLECTION AND ANALYSIS: We used standard
      methodological procedures as expected by The Cochrane Collaboration. We carried
      out meta-analyses only for cardiovascular death, as other outcomes were reported
      too infrequently. We expressed effect sizes as risk ratios (RRs), and we used
      random-effects models. MAIN RESULTS: We included eight trials of influenza
      vaccination compared with placebo or no vaccination, with 12,029 participants
      receiving at least one vaccination or control treatment. We included six new
      studies (n = 11,251), in addition to the two included in the previous version of
      the review. Four of these trials (n = 10,347) focused on prevention of influenza
      in the general or elderly population and reported cardiovascular outcomes among
      their safety analyses; four trials (n = 1682) focused on prevention of
      cardiovascular events in patients with established coronary heart disease. These
      populations were analysed separately. Follow-up continued between 42 days and one
      year. Five RCTs showed deficits in at least three of the risk of bias criteria
      assessed. When reported (seven studies), vaccination provided adequate
      immunogenicity or protection against influenza. Cardiovascular mortality was
      reported by four secondary prevention trials and was significantly reduced by
      influenza vaccination overall (risk ratio (RR) 0.45, 95% confidence interval (CI)
      0.26 to 0.76; P value 0.003) with no significant heterogeneity between studies,
      and by three trials reporting cardiovascular mortality as part of their safety
      analyses when the numbers of events were too small to permit conclusions. In
      studies of patients with coronary heart disease, composite outcomes of
      cardiovascular events tended to be decreased with influenza vaccination compared
      with placebo. Generally no significant difference was found between comparison
      groups regarding individual outcomes such as myocardial infarction. AUTHORS'
      CONCLUSIONS: In patients with cardiovascular disease, influenza vaccination may
      reduce cardiovascular mortality and combined cardiovascular events. However,
      studies had some risk of bias, and results were not always consistent, so
      additional higher-quality evidence is necessary to confirm these findings. Not
      enough evidence was available to establish whether influenza vaccination has a
      role to play in the primary prevention of cardiovascular disease.

PMID- 25940443
TI  - [Huntington's disease].
AB  - BACKGROUND: Huntington's disease (HD) is a progressive neurodegenerative disorder
      characterized by hyperkinetic movements, psychiatric (e.g. depression and
      psychosis) and cognitive symptoms (frontal lobe dementia). In Germany
      approximately 8000 patients suffer from HD. OBJECTIVES: The paper reviews the
      clinical course, epidemiology, genetics, differential diagnoses, pathophysiology,
      symptomatics and causal treatment options. METHODS: Publications on animal and
      human HD studies and trials and reviews available in Medline have been taken into
      account. RESULTS: Only genetic testing allows diagnostic certainty. The CAG
      repeat length influences age of onset, disease course and life expectancy. The
      mechanism by which mutant huntingtin protein (mHTT) causes HD is complex and
      poorly understood but leads to cell death, in particular in striatal neurons. In
      clinical trials antioxidants (e.g. coenzyme Q10), selisistat, PBT2, cysteamine, N
      methyl-D-aspartate (NMDA)-receptor antagonists and tyrosine kinase B receptor
      agonists have been studied in HD. CONCLUSION: No disease-modifying therapy is
      currently available for HD; however, gene silencing, e.g. through RNA
      interference, is a promising technique which could lead to effective therapies in
      due course.

PMID- 25940445
TI  - Magnetically induced forward scattering at visible wavelengths in silicon
      nanosphere oligomers.
AB  - Electromagnetically induced transparency is a type of quantum interference that
      induces near-zero reflection and near-perfect transmission. As a classical
      analogy, metal nanostructure plasmonic 'molecules' produce plasmon-induced
      transparency conventionally. Herein, an electromagnetically induced transparency
      interaction is demonstrated in silicon nanosphere oligomers, wherein the strong
      magnetic resonance couples with the electric gap mode effectively to markedly
      suppress reflection. As a result, a narrow-band transparency window created at
      visible wavelengths, called magnetically induced transparency, is easily realized
      in nearly touching silicon nanospheres, exhibiting low dependence on the number
      of spheres and aggregate states compared with plasmon induced transparency. A
      hybridization mechanism between magnetic and electric modes is proposed to pursue
      the physical origin, which is crucial to build all-dielectric metamaterials.
      Remarkably, magnetic induced transparency effect exhibiting near-zero reflection
      and near-perfect transmission causes light to propagate with no extra phase
      change. This makes silicon nanosphere oligomers promising as a unit cell in
      epsilon-near-zero metamaterials. 

PMID- 25940446
TI  - Rapid determination of 4-aminobutyric acid and L-glutamic acid in biological
      decarboxylation process by capillary electrophoresis-mass spectrometry.
AB  - 4-Aminobutylic acid (GABA) is a monomer of plastic polyamide 4. Bio-based
      polyamide 4 can be produced by using GABA obtained from biomass. The production
      of L-glutamic acid (Glu) from biomass has been established. GABA is produced by
      decarboxylation of Glu in biological process. High-performance liquid
      chromatography (HPLC) with derivatization is generally used to determine the
      concentration of GABA and Glu in reacted solution samples for the efficient
      production of GABA. In this study, we have investigated the rapid determination
      of GABA and Glu by capillary electrophoresis-mass spectrometry (CE-MS) without
      derivatization. The determination was achieved with the use of a shortened
      capillary, a new internal standard for GABA, and optimization of sheath liquid
      composition. Determined concentrations of GABA and Glu by CE-MS were compared
      with those by pre-column derivatization HPLC with phenylisothiocyanate. The
      determined values by CE-MS were close to those by HPLC with pre-column
      derivatization. These results suggest that the determination of GABA and Glu in
      reacted solution is rapid and simplified by the use of CE-MS. 

PMID- 25940447
TI  - Proton therapy for esthesioneuroblastoma: Can we shed some light on a murky
      topic?

PMID- 25940449
TI  - How could we offer support to doctors who fail examinations?

PMID- 25940450
TI  - Structural and Nutritional Properties of Pasta from Triticum monococcum and
      Triticum durum Species. A Combined 1H NMR, MRI, and Digestibility Study.
AB  - The aim of the present study was to characterize the structure of two different
      types of pasta, namely Triticum turgidum ssp. durum (cv. Saragolla) and Triticum
      monococcum ssp. monococcum (cv. Monlis), under different processing conditions.
      MRI analysis and NMR spectroscopy (i.e., T1 and T2 NMR relaxation times and
      diffusion parameters) were conducted on pasta, and (1)H NMR spectroscopic
      analysis of the chemical compounds released by pasta samples during the cooking
      process was performed. In addition, starch digestibility (enzimatically
      determined) was also investigated. The NMR results indicated that Saragolla pasta
      has a more compact structure, ascribed to pasta network and in particular to
      different technological gluten properties, that mainly determine the lower
      ability of Monlis pasta in binding water. These results correlate well with the
      lower rate of starch hydrolysis measured for Monlis pasta compared to Saragolla
      when both are dried at high temperature. 

PMID- 25940448
TI  - Phenotype-based clustering of glycosylation-related genes by RNAi-mediated gene
      silencing.
AB  - Glycan structures are synthesized by a series of reactions conducted by
      glycosylation-related (GR) proteins such as glycosyltransferases, glycan
      modifying enzymes, and nucleotide-sugar transporters. For example, the common
      core region of glycosaminoglycans (GAGs) is sequentially synthesized by peptide-O
      xylosyltransferase, beta1,4-galactosyltransferase I, beta1,3
      galactosyltransferase II, and beta1,3-glucuronyltransferase. This raises the
      possibility that functional impairment of GR proteins involved in synthesis of
      the same glycan might result in the same phenotypic abnormality. To examine this
      possibility, comprehensive silencing of genes encoding GR and proteoglycan core
      proteins was conducted in Drosophila. Drosophila GR candidate genes (125) were
      classified into five functional groups for synthesis of GAGs, N-linked, O-linked,
      Notch-related, and unknown glycans. Spatiotemporally regulated silencing caused a
      range of malformed phenotypes that fell into three types: extra veins, thick
      veins, and depigmentation. The clustered phenotypes reflected the biosynthetic
      pathways of GAGs, Fringe-dependent glycan on Notch, and glycans placed at or near
      nonreducing ends (herein termed terminal domains of glycans). Based on the
      phenotypic clustering, CG33145 was predicted to be involved in formation of
      terminal domains. Our further analysis showed that CG33145 exhibited
      galactosyltransferase activity in synthesis of terminal N-linked glycans.
      Phenotypic clustering, therefore, has potential for the functional prediction of
      novel GR genes. 

PMID- 25940451
TI  - Nurses' views regarding implementing advance care planning for older people: a
      systematic review and synthesis of qualitative studies.
AB  - AIMS AND OBJECTIVES: To explore nurses' views regarding implementing advance care
      planning for older people. BACKGROUND: Advance care planning is recommended as a
      way for older people to discuss their future care with family members and health
      professionals. Nurses play key roles in the process of advance care planning,
      including ensuring that patients are informed of their rights and that decisions
      are known to, and respected by, the health care team. Thus, understanding of
      nurses' experiences and perspectives regarding implementing advance care planning
      for older people is a significant topic for review. DESIGN: Qualitative meta
      synthesis. METHODS: Four databases including CINAHL plus, Medline [EBSCOhost],
      EMBASE, and PsycINFO were searched, and 1844 articles were initially screened.
      Finally, 18 articles were critically appraised and a thematic synthesis was
      undertaken. RESULTS: Four themes were identified regarding implementation of
      advance care planning: perceived disadvantages and advantages of advance
      directives; nurses' responsibility and roles; facilitators and barriers; and
      nurses' needs and recommendations. Nurses felt that advance directives provided
      more advantages than disadvantages. Nurses generally believed that they were well
      positioned to engage in advance care planning conversations. Nurses perceived
      barriers relating to older people, families, environment, time, culture, cost,
      language and knowledge of health care teams with regard to advance care planning.
      In nurses' needs, education and support were highlighted. CONCLUSIONS: This study
      provides useful knowledge for implementing advance care planning through
      illustrating nurses' experiences and perspectives. The results showed that nurses
      were more concerned about barriers in relation to working environment, teamwork,
      time and knowledge of health care team members than older people's
      characteristics, when implementing advance care planning. RELEVANCE TO CLINICAL
      PRACTICE: The findings provide nurses and administrators with information to
      develop related policies and education. Additionally, the appointment of nurses
      to formal roles related to advance care planning is appropriate and warranted.

PMID- 25940452
TI  - Bone density and microarchitecture in endogenous hypercortisolism.
AB  - OBJECTIVE: Osteoporosis is a serious and underestimated complication of
      endogenous hypercortisolism that results in an increased risk of fractures, even
      in patients with normal or slightly decreased bone mineral density (BMD).
      Alterations in bone microarchitecture, a very important component of bone
      quality, may explain bone fragility. The aim of this study was to investigate
      bone density and microarchitecture in a cohort of patients with endogenous
      Cushing's syndrome (CS). DESIGN: Cross-sectional study. PATIENTS: Thirty patients
      with endogenous active CS and fifty-one age-, sex- and body mass index-matched
      controls were included. MEASUREMENTS: Participants were studied for areal BMD
      (dual-energy X-ray absorptiometry) of the lumbar spine (LS), femoral neck (FN),
      total femur (TF) and radius (33%), and for volumetric bone density (vBMD) and
      structure using high-resolution peripheral quantitative computed tomography (HR
      pQCT) of the distal radius and distal tibia. RESULTS: Patients with active CS
      exhibited lower areal BMD and Z-score values in the LS, FN and TF (P < 0.003 for
      all comparisons). At HR-pQCT, the patients with CS also had lower cortical area
      (P = 0.009 at the radius and P = 0.002 at the tibia), lower cortical thickness (P
      = 0.02 at the radius and P = 0.002 at the tibia), lower cortical density (P =
      0.008 at the tibia) and lower total vBMD (P = 0.002 at the tibia). After the
      exclusion of hypogonadal individuals, the patients with CS maintained the same
      microarchitectural and densitometric alterations described above. CONCLUSIONS:
      Endogenous hypercortisolism has deleterious effects on bone, especially on
      cortical bone microstructure. These effects seem to be a more important
      determinant of bone impairment than gonadal status.

PMID- 25940454
TI  - The effect of alcohol hangover on the ability to ride a bicycle.
AB  - To investigate the effects of alcohol on the ability to ride a bicycle, practical
      cycling tests were carried out at different blood alcohol concentrations (BAC).
      For this purpose, various alcoholic beverages could be consumed from around 2
      p.m. until 11 p.m. Afterwards, the test persons spent the night on the trial site
      and were provided with dormitory sleeping accommodation. On the following
      morning, beginning at around 8 a.m., a final cycling test was performed. The
      performances of those test persons who had returned to state of soberness and of
      those with residual blood alcohol levels were compared to the performances on the
      day before. The practical ability to ride a bicycle was significantly reduced in
      the postalcoholic state compared to the rides of the day before. The relative
      cycling performance in the postalcoholic state was comparable to the rides under
      the influence of BAC of around 0.30 g/kg. There were no remarkable differences
      between the groups with and without residual blood alcohol levels regarding the
      rides on the next morning. Therefore, it can be assumed that the direct influence
      of residual blood alcohol levels plays a minor role for the ability to ride a
      bicycle in the postalcoholic state. Instead, the side effects of the high amounts
      of alcohol that were consumed the night before are crucial.

PMID- 25940453
TI  - The Association Between PICC Use and Venous Thromboembolism in Upper and Lower
      Extremities.
AB  - BACKGROUND: Peripherally inserted central catheters are associated with upper
      extremity deep vein thrombosis. Whether they also are associated with lower
      extremity deep vein thrombosis or pulmonary embolism is unknown. We examined the
      risk of venous thromboembolism in deep veins of the arm, leg, and chest after
      peripherally inserted central catheter placement. METHODS: We conducted a
      multicenter, retrospective cohort study of 76,242 hospitalized medical patients
      from 48 Michigan hospitals. Peripherally inserted central catheter presence,
      comorbidities, venous thrombosis risk factors, and thrombotic events within 90
      days from hospital admission were ascertained by phone and record review. Cox
      proportional hazards models were fit to examine the association between
      peripherally inserted central catheter placement and 90-day hazard of upper- and
      lower-extremity deep vein thrombosis or pulmonary embolism, adjusting for patient
      level characteristics and natural clustering within hospitals. RESULTS: A total
      of 3790 patients received a peripherally inserted central catheter during
      hospitalization. From hospital admission to 90 days, 876 thromboembolic events
      (208 upper-extremity deep vein thromboses, 372 lower-extremity deep vein
      thromboses, and 296 pulmonary emboli) were identified. After risk adjustment,
      peripherally inserted central catheter use was independently associated with all
      cause venous thromboembolism (hazard ratio [HR], 3.16; 95% confidence interval
      [CI], 2.59-3.85), upper-extremity deep vein thrombosis (HR, 10.49; 95% CI, 7.79
      14.11), and lower-extremity deep vein thrombosis (HR, 1.48; 95% CI, 1.02-2.15).
      Peripherally inserted central catheter use was not associated with pulmonary
      embolism (HR, 1.34; 95% CI, 0.86-2.06). Results were robust to sensitivity
      analyses incorporating receipt of pharmacologic prophylaxis during
      hospitalization. CONCLUSIONS: Peripherally inserted central catheter use is
      associated with upper- and lower-extremity deep vein thrombosis. Weighing the
      thrombotic risks conferred by peripherally inserted central catheters against
      clinical benefits seems necessary.

PMID- 25940455
TI  - Maternal occupation during pregnancy, birth weight, and length of gestation:
      combined analysis of 13 European birth cohorts.
AB  - OBJECTIVES: We assessed whether maternal employment during pregnancy - overall
      and in selected occupational sectors - is associated with birth weight, small for
      gestational age (SGA), term low birth weight (LBW), length of gestation, and
      preterm delivery in a population-based birth cohort design. METHODS: We used data
      from >200 000 mother-child pairs enrolled in 13 European birth cohorts and
      compared employed versus non-employed women. Among employees, we defined groups
      of occupations representing the main sectors of employment for women where
      potential reproductive hazards are considered to be present. The comparison group
      comprised all other employed women not included in the occupational sector being
      assessed. We performed meta-analyses of cohort-specific estimates and explored
      heterogeneity. RESULTS: Employees had a lower risk of preterm delivery than non
      employees [adjusted odds ratio (OR adj) 0.86, 95% confidence interval (95% CI)
      0.81-0.91]. Working in most of the occupational sectors studied was not
      associated with adverse birth outcomes. Being employed as a nurse was associated
      with lower risk SGA infants (OR adj0.91, 95% CI 0.84-0.99) whereas food industry
      workers had an increased risk of preterm delivery (OR adj1.50, 95% CI 1.12-2.02).
      There was little evidence for heterogeneity between cohorts. CONCLUSIONS: This
      study suggests that, overall, employment during pregnancy is associated with a
      reduction in the risk of preterm birth and that work in certain occupations may
      affect pregnancy outcomes. This exploratory study provides an important platform
      on which to base further prospective studies focused on the potential
      consequences of maternal occupational exposures during pregnancy on child
      development.

PMID- 25940456
TI  - Mastitis, a Radiographic, Clinical, and Histopathologic Review.
AB  - Mastitis is a benign inflammatory process of the breast with heterogeneous
      histopathological findings, which clinically and radiographically may mimic a
      mammary carcinoma. We undertook a retrospective study on 37 cases of mastitis in
      our institution to correlate the radiographic imaging features and the clinical
      presentation with the histopathological findings. Histologically, there were 21
      granulomatous, 7 fibrous, 3 plasma cell, 3 lupus, 2 lymphocytic, and 1 case of
      acute mastitis. Radiographically, 16/25 (64%) patients with ultrasound studies
      showed irregular hypoechoic masses suspicious for malignancy. Clinically, 38% of
      patients had an associated systemic disease. 

PMID- 25940457
TI  - A new instrumented method for the evaluation of gait initiation and step climbing
      based on inertial sensors: a pilot application in Parkinson's disease.
AB  - BACKGROUND: Step climbing is a demanding task required for personal autonomy in
      daily living. Anticipatory Postural Adjustments (APAs) preceding gait initiation
      have been widely investigated revealing to be hypometric in Parkinson's disease
      (PD) with consequences in movement initiation. However, only few studies focused
      on APAs prior to step climbing. In this work, a novel method based on wearable
      inertial sensors for the analysis of APAs preceding gait initiation and step
      climbing was developed to further understand dynamic balance control. Validity
      and sensitivity of the method have been evaluated. METHODS: Eleven PD and 20
      healthy subjects were asked to perform two transitional tasks from quiet standing
      to level walking, and to step climbing respectively. All the participants wore
      two inertial sensors, placed on the trunk (L2-L4) and laterally on the shank. In
      addition, a validation group composed of healthy subjects and 5 PD patients
      performed the tasks on two force platforms. Correlation between parameters from
      wearable sensors and force platforms was evaluated. Temporal parameters and trunk
      acceleration from PD and healthy subjects were analyzed. RESULTS: Significant
      correlation was found for the validation group between temporal parameters
      extracted from wearable sensors and force platforms and between medio-lateral
      component of trunk acceleration and correspondent COP displacement. These results
      support the validity of the method for evaluating APAs prior to both gait
      initiation and step climbing. Comparison between PD subjects and a subgroup of
      healthy controls confirms a reduction in PD of the medio-lateral acceleration of
      the trunk during the imbalance phase in the gait initiation task and shows
      similar trends during the imbalance and unloading phase of the step climbing
      task. Interestingly, PD subjects presented difficulties in adapting the medio
      lateral amplitude of the imbalance phase to the specific task needs. CONCLUSIONS:
      Validity of the method was confirmed by the significant correlation between
      parameters extracted from wearable sensors and force platforms. Sensitivity was
      proved by the capability to discriminate PD subjects from healthy controls. Our
      findings support the applicability of the method to subjects of different age.
      This method could be a possible valid instrument for a better understanding of
      feed-forward anticipatory strategies.

PMID- 25940460
TI  - Use of selective serotonin reuptake inhibitors and bone mass in adolescents: An
      NHANES study.
AB  - CONTEXT: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed
      medications to treat depression and anxiety. SSRIs exert their effects by
      inhibiting the serotonin transporter and modulating extracellular serotonin
      levels, a neurotransmitter that has been shown to affect bone metabolism in
      animals. Studies in adults suggest a negative association between SSRI use and
      bone mineral density (BMD), greater rates of bone loss with SSRI use and
      increased risk of fractures. However, the results on bone mass have been
      inconsistent. Furthermore, there is a dearth of studies examining an association
      between SSRI use and bone mass in the pediatric and adolescent age group.
      OBJECTIVE: To investigate associations between SSRI use and bone mass in
      adolescents. DESIGN: Cross-sectional analysis of data from the 2005-2010 National
      Health and Nutrition Examination Study (NHANES). PARTICIPANTS: 4303 NHANES
      participants aged 12-20 years. The mean age was 15.65+/-2.42 years. MAIN
      OUTCOMES: Total femur, femoral neck and lumbar spine bone mineral content (BMC)
      and BMD assessed via dual-energy X-ray absorptiometry (DXA). RESULTS: 62 out of
      4303 subjects used SSRIs. SSRI use was an independent predictor of bone mass
      after adjusting for age, gender, height and weight Z score, socioeconomic status,
      physical activity, serum cotinine level and race/ethnicity. After multivariable
      adjustment, total femur BMC was 8.8% lower among SSRI users versus non-users
      (mean difference 2.98 g, SE+/-0.105 g, p=0.0006), while total femur BMD was 6.1%
      lower (mean difference 0.06 g/cm2, SE+/-0.002 g/cm2, p=0.016). Femoral neck BMC
      and BMD and lumbar spine BMC were similarly negatively associated with SSRI use.
      Compared to nonusers, lumbar spine BMC was 7% lower among SSRI users (mean
      difference 0.97 g, SE+/-0.048g, p=0.02) and BMD was 3.2% lower (mean difference
      0.03 g/cm2, SE+/-0.015 g/cm2, p=0.09). Sub-analysis of those individuals treated
      for more than 6 months yield similar results. Finally, the association of SSRIs
      with bone mass persisted after excluding individuals with Body Mass Index (BMI)
      less than 5th percentile thus accounting for the possible confounding effect of
      anorexia nervosa, which can be treated with SSRIs. CONCLUSION: In this NHANES
      study, adolescents treated with SSRIs had lower DXA measurements of the total
      femur and lumbar spine compared to SSRI non-users. These findings support the
      need for future prospective studies to examine the effects of SSRI use on bone
      mass in adolescents.

PMID- 25940459
TI  - A comparison of tissue engineering based repair of calvarial defects using
      adipose stem cells from normal and osteoporotic rats.
AB  - Repairing large bone defects presents a significant challenge, especially in
      those people who have a limited regenerative capacity such as in osteoporotic
      (OP) patients. The aim of this study was to compare adipose stem cells (ASCs)
      from both normal (NORM) and ovariectomized (OVX) rats in osteogenic potential
      using both in vitro and in vivo models. After successful establishment of a rat
      OP model, we found that ASCs from OVX rats exhibited a comparable proliferation
      capacity to those from NORM rats but had significantly higher adipogenic and
      relatively lower osteogenic potential. Thirty-two weeks post-implantation with
      poly(lactic-co-glycolic acid) (PLGA) alone or PLGA seeded with osteogenic-induced
      ASCs for critical-size calvarial defects, the data from Herovici's collagen
      staining and micro-computed tomography suggested that the implantation of ASC
      PLGA constructs exhibited a higher bone volume density compared to the PLGA alone
      group, especially in the NORM rat group. Intriguingly, the defects from OVX rats
      exhibited a higher bone volume density compared to NORM rats, especially for
      implantation of the PLGA alone group. Our results indicated that ASC based tissue
      constructs are more beneficial for the repair of calvarial defects in NORM rats
      while implantation of PLGA scaffold contributed to defect regeneration in OVX
      rats. 

PMID- 25940461
TI  - Sex ratio of White Stork Ciconia ciconia in different environments of Poland.
AB  - The aim of this study was to analyze the variation in sex ratio of White Stork
      Ciconia ciconia chicks from differentiated Poland environments. We took under a
      consideration the impact of Cd and Pb for establish differences among sex ratio
      in chicks. We also study multiplex PCR employment for establish gender
      considerations. We collected blood samples via venipuncture of brachial vein of
      chicks during 2006-2008 breeding seasons at the Odra meadows (SW-Poland;
      control), which were compared with those from suburbs (SW-Poland), and from
      copper smelter (S-Poland; polluted) and from swamps near Baltic Sea. We found
      differences among sex ratio in White Stork chicks from types of environment. Male
      participation in sex structure is importantly higher in each type of environment
      excluded suburban areas. Differences in White Stork sex ratio according to the
      degree of environmental degradation expressed by Cd and Pb and sex-environment
      metal interactions testify about the impact of these metals upon sex ratios in
      storks. Simultaneously, as a result of multiplex PCR, 18S ribosome gene, which
      served as internal control of PCR, was amplified in male and female storks. It
      means that it is possible to use primers designed for chicken in order to
      replicate this fragment of genome in White Stork. Moreover, the use of Oriental
      White Stork Ciconia boyciana W- chromosome specific primers makes it possible to
      determine the sex of C. ciconia chicks. Many factors make sex ratio of White
      Stork changes in subsequent breeding seasons, which depend significantly on
      specific environmental parameters that shape individual detailed defense
      mechanisms. 

PMID- 25940463
TI  - pH and ionic strength effects on the binding constant between a nitrogen
      containing polycyclic aromatic compound and humic acid.
AB  - Polycyclic aromatic compounds (PACs) are widespread environmental pollutants with
      a high potential to act as human carcinogens and mutagens. The behavior of PACs
      is significantly affected by their interactions with dissolved organic matter
      (DOM), such as their transport, solubility, bioavailability, and bioaccumulation
      in the aquatic environment. Being a basic PAC, benzo(h)quinoline (BQ) is the
      dominant species, as the solution's pH value is higher than BQ's pK a (pK a of BQ
      = 4.2). In contrast, benzo(h)quinolinium (BQH(+)) is the major species, as the
      solution's pH value is lower than its pK a. The binding constant (K DOC),
      measured by fluorescence quenching, between BQ/BQH(+) and Leonardite humic acid
      (LHA) would decrease 70 to 95 % and 20 to 90 % when increasing the ionic strength
      in acidic and neutral to basic conditions, respectively. The results can be
      attributed to the added cation (Na(+) and Mg(2+)), which forms a bridge with LHA
      and enhances the intramolecular reaction among these functional groups, therefore
      inducing the coiling up within the LHA molecule. In addition, the decrease of the
      K DOC with added MgCl2/MgSO4 (75-95 %) is higher than that with added NaCl/Na2SO4
      (20-75 %), indicating that the K DOC was affected by the charge density of
      cations. The fluorescence intensity of BQH(+) in the absence of LHA (F 0) was
      found to decay only in the acidic solution with Cl(-), suggesting that Cl(-)
      might be a heavy atom serving as a quencher in an acidic solution. 

PMID- 25940462
TI  - Biomarkers of oxidative stress in rat for assessing toxicological effects of
      heavy metal pollution in river water.
AB  - Increasing use of heavy metals in various fields, their environmental
      persistency, and poor regulatory efforts have significantly increased their
      fraction in river water. We studied the effect of Musi river water pollution on
      oxidative stress biomarkers and histopathology in rat after 28 days repeated oral
      treatment. River water analysis showed the presence of Zn and Pb at mg/l
      concentration and Ag, As, Ba, Cd, Co, Cr, Cu, Mn, Mo, Ni, Sn, and Sb at MUg/l
      concentration. River water treatment resulted in a dose-dependent accumulation of
      metals in rat organs, being more in liver followed by kidney and brain. Metal
      content in both control and low-dose group rat organs was below limit of
      detection. However, metal bioaccumulation in high- and medium-dose group organs
      as follows: liver-Zn (21.4 & 14.5 MUg/g), Cu (8.3 & 3.6 MUg/g), and Pb (8.2 & 0.4
      MUg/g); kidney-Zn (16.2 & 7.9 MUg/g), Cu (3.5 & 1.4 MUg/g), Mn (2.9 & 0.5 MUg/g),
      and Pb (2.6 & 0.5 MUg/g); and brain-Zn (2.4 & 1.1 MUg/g), and Ni (1 & 0.3 MUg/g).
      These metals were present at high concentrations in respective organs than other
      metals. The increased heavy metal concentration in treated rat resulted
      significant increase in superoxide dismutase, glutathione peroxidase, glutathione
      reductase, glutathione S transferase enzymes activity, and lipid peroxidation in
      a dose-dependent manner. However, glutathione content and catalase activity were
      significantly decreased in treated rat organs. Histopathological examination also
      confirmed morphological changes in rat organs due to polluted river water
      treatment. In conclusion, the findings of this study clearly indicate the
      oxidative stress condition in rat organs due to repeated oral treatment of
      polluted Musi river water. 

PMID- 25940464
TI  - The performance of chitosan/montmorillonite nanocomposite during the flocculation
      and floc storage processes of Microcystis aeruginosa cells.
AB  - This study aimed to investigate the performance of chitosan-modified nano-sized
      montmorillonite (CTS/NMMT) during the flocculation of Microcystis aeruginosa
      (MA). The release of intracellular microcystins (MCs) caused by the damage of
      intact MA cells during the flocculation and floc storage processes was also
      comprehensively evaluated through scanning electron microscopy (SEM) and
      measurement of K(+) and Mg(2+) release. With the application of the Box-Behnken
      experimental design combined with response surface methodology, the quadratic
      statistical model was established to predict and optimize the interactive effects
      of content of CTS/NMMT, weight ratio of NMMT to CTS, and agitation time on the
      removal efficiency of MA cells. A maximum removal of 94.7 % MA cells was observed
      with content of CTS/NMMT 300-320 mg L(-1), weight ratio of NMMT to CTS 14-16, and
      agitation time 16-50 min. During the flocculation process, CTS/NMMT aggregated MA
      cells as flocs and served as a protection shield for cells. The extracellular and
      intracellular microcystin-leucine-arginine (MC-LR) decreased remarkably and the
      yield of intracellular MC-LR showed a decreasing trend during the flocculation.
      The cell integrity was slightly damaged by the mechanical actions rather than by
      the flocculant. During the floc storage process, cell lysis and membrane damage
      were remarkably aggravated. The noticeable increase of K(+) and Mg(2+) release
      indicated that CTS/NMMT damaged the integrity of most MA cells in the flocs and
      liberated the intracellular MC-LR. Meanwhile, NMMT and CTS polymers assisted the
      adsorptive removal of extracellular MC-LR released to water. The flocs should be
      timely treated within 12 h to prevent the leakage of MCs.

PMID- 25940465
TI  - The associations between metals/metalloids concentrations in blood plasma of Hong
      Kong residents and their seafood diet, smoking habit, body mass index and age.
AB  - The concentrations of metals/metalloids in blood plasma collected from 111
      healthy residents (51 female, 60 male) in Hong Kong (obtained from the Hong Kong
      Red Cross Blood Transfusion Service, from March to April 2008) were quantified by
      means of a double-focusing sector field inductively coupled plasma optical
      emission spectrometer (ICP-OES). Results showed that concentrations of these
      toxic metals such as Hg, Cd, and Pb in Hong Kong residents were not serious when
      compared with other countries. Males accumulated significantly higher (p < 0.05
      or 0.01) Fe (female 0.92 mg/L; male 1.28), Sn (0.44 MUg/L; 0.60), Cr (0.77;
      0.90), Hg (1.01; 1.73), and Pb (23.4; 31.6) than females. Smokers accumulated
      significantly higher (p < 0.05) Cd (smoker 0.27 MUg/L; nonsmoker 0.17) and Pb
      (32.8; 17.6) than nonsmokers. Positive correlations were found between
      concentrations of As, Cd, Pb, and Hg, with respect to seafood diet habit, body
      mass index (BMI), and age. More intensive studies involving more samples are
      needed before a more definite conclusion can be drawn, especially on the causal
      relationships between concentrations of metals/metalloids with dietary preference
      and lifestyle of the general public. 

PMID- 25940466
TI  - Comparison on the molecular response profiles between nano zinc oxide (ZnO)
      particles and free zinc ion using a genome-wide toxicogenomics approach.
AB  - Increasing production and applications of nano zinc oxide particles (nano-ZnO)
      enhances the probability of its exposure in occupational and environmental
      settings, but toxicity studies are still limited. Taking the free Zn ion (Zn(2+))
      as a control, cytotoxicity of a commercially available nano-ZnO was assessed with
      a 6-h exposure in Escherichia coli (E. coli). The fitted dose-cytotoxicity curve
      for ZnCl2 was significantly sharper than that from nano-ZnO. Then, a genome-wide
      gene expression profile following exposure to nano-ZnO was conducted by use of a
      live cell reporter assay system with library of 1820 modified green fluorescent
      protein (GFP)-expressing promoter reporter vectors constructed from E. coli K12
      strains, which resulted in 387 significantly altered genes in bacterial (p <
      0.001). These altered genes were enriched into ten biological processing and two
      cell components (p < 0.05) terms through statistical hypergeometric testing,
      strongly suggesting that exposure to nano-ZnO would result a great disturbance on
      the functional gene product synthesis processing, such as translation, gene
      expression, RNA modification, and structural constituent of ribosome. The pattern
      of expression of 37 genes altered by nano-ZnO (fold change>2) was different from
      the profile following exposure to 6 mg/L of free zinc ion. The result indicates
      that these two Zn forms might cause toxicity to bacterial in different modes of
      action. Our results underscore the importance of understanding the adverse
      effects elicited by nano-ZnO after entering aquatic environment. 

PMID- 25940467
TI  - Comparative sensitivity of the cnidarian Exaiptasia pallida and a standard
      toxicity test suite: testing whole effluents intended for ocean disposal.
AB  - The sea anemone Exaiptasia pallida (formally Aiptasia pulchella) has been
      identified as a valuable test species for tropical marine ecotoxicology. Here,
      the sensitivities of newly developed endpoints for E. pallida to two unidentified
      whole effluents were compared to a standard suite of temperate toxicity test
      species and endpoints that are commonly used in toxicological risk assessments
      for tropical marine environments. For whole effluent 1 (WE1), a 96-h lethal
      concentration 50 % (LC50) of 40 (95 % confidence intervals, 30-54) % v/v and a 12
      day LC50 of 12 (9-15) % v/v were estimated for E. pallida, exhibiting a
      significantly higher sensitivity than standard sub-lethal endpoints in
      Allorchestes compressa (96-h effective concentration 50 % (EC50) of >100 % v/v
      for immobilisation) and Hormosira banksii (72-h EC50 of >100 % v/v for
      germination), and a similar sensitivity to Mytilus edulis galloprovincialis
      larval development with a 48-h LC50 of 29 (28-30) % v/v. Sub-lethal effects of
      whole effluent 2 (WE2) on E. pallida pedal lacerate development resulted in an 8
      day EC50 of 7 (3-11) % v/v, demonstrating comparable sensitivity of this endpoint
      to standardised sub-lethal endpoints in H. banksii (72-h EC50 of 11 (10-11) % v/v
      for germination), M. edulis galloprovincialis (48-h EC50 for larval development
      of 12 (9-14) % v/v) and Heliocidaris tuberculata (1-h EC50 of 13 (12-14) % v/v
      for fertilisation; 72-h EC50 of 26 (25-27) % v/v for larval development) and a
      significantly higher sensitivity than A. compressa immobilisation (96-h EC50 of
      >100 % v/v). The sensitivity of E. pallida compared to a standard test species
      suite highlights the value in standardising the newly developed toxicity test
      methods for inclusion in routine toxicological risk assessment of complex whole
      effluents. Importantly, this species provides an additional taxonomic group to
      the test species that are currently available for tropical marine ecotoxicology
      and, being a cnidarian, may represent important tropical marine environments
      including coral reefs. 

PMID- 25940468
TI  - Intensive rice agriculture deteriorates the quality of shallow groundwater in a
      typical agricultural catchment in subtropical central China.
AB  - High nitrogen (N) concentrations in rural domestic water supplies have been
      attributed to excessive agricultural N leaching into shallow groundwater systems;
      therefore, it is important to determine the impact of agriculture (e.g., rice
      production) on groundwater quality. To understand the impact of agricultural land
      use on the N concentrations in the shallow groundwater in subtropical central
      China, a large observation program was established to observe ammonium-N (NH4-N),
      nitrate-N (NO3-N), and total N (TN) concentrations in 161 groundwater observation
      wells from April 2010 to November 2012. The results indicated that the median
      values of NH4-N, NO3-N, and TN concentrations in the groundwater were 0.15, 0.39,
      and 1.38 mg N L(-1), respectively. A total of 36.3 % of the water samples were
      categorized as NH4-N pollution, and only a small portion of the samples were
      categorized as NO3-N pollution, based on the Chinese Environmental Quality
      Standards for Groundwater of GB/T 14848-93 (General Administration of Quality
      Supervision of China, 1993). These results indicated of moderate groundwater NH4
      N pollution, which was mainly attributed to intensive rice agriculture with great
      N fertilizer application rates in the catchment. In addition, tea and vegetable
      fields showed higher groundwater NO3-N and TN concentrations than other
      agricultural land use types. The factorial correspondence analysis (FCA)
      suggested that the flooded agricultural land use types (e.g., single-rice and
      double-rice) had potential to impose NH4-N pollution, particularly in the soil
      exhausting season during from July to October. And, the great N fertilizer
      application rates could lead to a worse NO3-N and TN pollution in shallow
      groundwater. Hence, to protect groundwater quality and minimize NH4-N pollution,
      managing optimal fertilizer application and applying appropriate agricultural
      land use types should be implemented in the region. 

PMID- 25940469
TI  - Ion-exchange method in the collection of nitrate from freshwater ecosystems for
      nitrogen and oxygen isotope analysis: a review.
AB  - Nitrate (NO3(-)) contamination of freshwater is considered one of the most
      prevalent global environmental problems. Dual stable isotopic compositions
      (delta(15)N and delta(18)O) of NO3(-) can provide helpful information and have
      been well documented as being a powerful tool to track the source of NO3(-) in
      freshwater ecosystems. The ion-exchange method is a reliable and precise
      technique for measuring the delta(15)N and delta(18)O of NO3(-) and has been
      widely employed to collect NO3(-) from freshwater ecosystems. This review
      summarizes and presents the principles, affecting factors and corresponding
      significant improvements of the ion-exchange method. Finally, potential
      improvements and perspectives for the applicability of this method are also
      discussed, as are suggestions for further research and development drawn from the
      overall conclusions.

PMID- 25940470
TI  - Crop protection, environment, health, and biodiversity: observations and outlook.

PMID- 25940471
TI  - Passive air sampling for determining the levels of ambient PCDD/Fs and their
      seasonal and spatial variations and inhalation risk in Shanghai, China.
AB  - The seasonal and spatial variations, compositional profiles, and possible sources
      of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs)
      in ambient air samples in Shanghai of China were investigated by passive air
      samplers, and the potential inhalation risks posed by these chemicals were
      evaluated. The following results were obtained: (1) The World Health Organization
      (WHO) toxic equivalency (TEQ) values for PCDD/Fs were in the range of 10.8-259 fg
      m(-3) (mean 63.4 fg m(-3)) in summer and 24.1-154 fg m(-3) (mean 83.4 fg m(-3))
      in winter. Atmospheric PCDD/F levels were in the following order: industrial
      areas > commercial and residential areas > rural areas. (2) 2,3,4,7,8-PeCDF (24
      %), 2,3,7,8-TeCDD (16 %), 1,2,3,7,8-PeCDD (13 %), and 2,3,7,8-TeCDF (12 %) were
      the predominant contributors to the TEQ of PCDD/Fs. (3) There was a slight
      seasonal trend with higher TEQ values in winter than in summer, which could be
      related to seasonal variations in the dispersion of PCDD/Fs in ambient air. (4)
      The children's daily intake was at the lower end of the range for the tolerable
      daily intake of PCDD/Fs recommended by WHO, which indicates that the inhalation
      risk of PCDD/Fs for local residents in Shanghai is relatively low. 

PMID- 25940472
TI  - Size distribution of total and water-soluble fractions of particle-bound elements
      assessment of possible risks via inhalation.
AB  - The size distribution of total and water-soluble elemental concentrations in six
      particle sizes <0.49, 0.49-0.97, 0.97-1.5, 1.5-3.0, 3.0-7.2, and 7.2-30 MUm was
      investigated in Thessaloniki area, N. Greece, at two sites representing urban
      traffic and urban-background character during the cold and warm period. The
      elements As, Cd, Cr, Cu, Pb, Ni, Zn, Ru, and Ir exhibited their highest mass
      portion in the fine particle mode (0.97-1.5 MUm), whereas Al, Ba, Ca, Fe, and Mn
      occurred predominately in the coarse particle mode (3.0-7.2 MUm). The water
      soluble elemental fractions exhibited significant spatiotemporal variations and
      particle size dependence. Possible non-carcinogenic and carcinogenic risks
      associated with inhalation of particle-bound elements based on total and water
      soluble concentrations were in acceptable levels. However, the cumulative risk
      for all potential particle-bound constituents has to be considered. 

PMID- 25940473
TI  - Sulfadiazine uptake and effects in common hazel (Corylus avellana L.).
AB  - Soil contamination by antibiotics is a possible consequence of animal husbandry
      waste, sewage sludge, and reclaimed water spreading in agriculture. In this
      study, 1-year-old hazel plants (Corylus avellana L.) were grown in pots for 64
      days in soil spiked with sulfadiazine (SDZ) in the range 0.01-100 mg kg(-1) soil.
      Leaf gas exchanges, fluorescence parameters and plant growth were measured
      regularly during the experiment, whereas plant biomass, sulfonamide
      concentrations in soil and plant tissues, and the quantitative variation of
      culturable bacterial endophytes in leaf petiole were analyzed at the end of the
      trial. During the experiment, photosynthesis and leaf transpiration as well as
      fluorescence parameters were progressively reduced by the antibiotic. Effects
      were more evident for leaf transpiration and for the highest SDZ spiking
      concentrations, whereas growth analyses did not reveal negative effects of the
      antibiotic. At the end of the trial, a high number of culturable endophytic
      bacteria in the leaf petiole of plants treated with 0.1 and 0.01 mg kg(-1) were
      observed, and SDZ was extractable from soil and plant roots for spiking
      concentrations >=1 mg kg(-1). Inside plants, the antibiotic was mainly stored at
      the root level with bioconcentration factors increasing with the spiking dose,
      and the hydroxylated derivate 4-OH-SDZ was the only metabolite detected. Overall
      results show that 1-year-old hazel plants can contribute to the reduction of
      sulfonamide concentrations in the environment, however, sensitive reactions to
      SDZ can be expected at the highest contamination levels. 

PMID- 25940474
TI  - A comparative study between the fluxes of trace elements in bulk atmospheric
      deposition at industrial, urban, traffic, and rural sites.
AB  - The input of trace elements via atmospheric deposition towards industrial, urban,
      traffic, and rural areas is quite different and depends on the intensity of the
      anthropogenic activity. A comparative study between the element deposition fluxes
      in four sampling sites (industrial, urban, traffic, and rural) of the Cantabria
      region (northern Spain) has been performed. Sampling was carried out monthly
      using a bulk (funnel bottle) sampler. The trace elements, As, Cd, Cr, Cu, Mn, Mo,
      Ni, Pb, Ti, Zn, and V, were determined in the water soluble and insoluble
      fractions of bulk deposition samples. The element deposition fluxes at the rural,
      urban, and traffic sites followed a similar order (Zn > Mn> > Cu ~ Ti > Pb > V ~
      Cr > Ni> > As ~ Mo > Cd). The most enriched elements were Cd, Zn, and Cu, while
      V, Ni, and Cr were less enriched. An extremely high deposition of Mn was found at
      the industrial site, leading to high enrichment factor values, resulting from the
      presence of a ferro-manganese/silico-manganese production plant in the vicinity
      of the sampling site. Important differences were found in the element
      solubilities in the studied sites; the element solubilities were higher at the
      traffic and rural sites, and lower at the urban and industrial sites. For all
      sites, Zn and Cd were the most soluble elements, whereas Cr and Ti were less
      soluble. The inter-site correlation coefficients for each element were calculated
      to assess the differences between the sites. The rural and traffic sites showed
      some similarities in the sources of trace elements; however, the sources of these
      elements at the industrial and rural sites were quite different. Additionally,
      the element fluxes measured in the insoluble fraction of the bulk atmospheric
      deposition exhibited a good correlation with the daily traffic volume at the
      traffic site. 

PMID- 25940475
TI  - Scenario-targeted toxicity assessment through multiple endpoint bioassays in a
      soil posing unacceptable environmental risk according to regulatory screening
      values.
AB  - Lanestosa is a chronically polluted site (derelict mine) where the soil
      (Lanestosa (LA) soil) exceeds screening values (SVs) of regulatory policies in
      force (Basque Country; Europe) for Zn, Pb and Cd. A scenario-targeted toxicity
      assessment was carried out on the basis of a multi-endpoint bioassay approach.
      Acute and chronic toxicity bioassays were conducted with selected test species
      (Vibrio fischeri, Dictyostelium discoideum, Lactuca sativa, Raphanus sativus and
      Eisenia fetida) in combination with chemical analysis of soils and elutriates and
      with bioaccumulation studies in earthworms. Besides, the toxicity profile was
      compared with that of the mine runoff (RO) soil and of a fresh artificially
      polluted soil (LAAPS) resembling LA soil pollutant profile. Extractability
      studies in LA soil revealed that Pb, Zn and Cd were highly available for exchange
      and/or release into the environment. Indeed, Pb and Zn were accumulated in
      earthworms and LA soil resulted to be toxic. Soil respiration, V. fischeri,
      vegetative and developmental cycles of D. discoideum and survival and juvenile
      production of E. fetida were severely affected. These results confirmed that LA
      soil had unacceptable environmental risk and demanded intervention. In contrast,
      although Pb and Zn concentrations in RO soil revealed also unacceptable risk,
      both metal extractability and toxicity were much lower than in LA soil. Thus,
      within the polluted site, the need for intervention varied between areas that
      posed dissimilar risk. Besides, since LAAPS, with a high exchangeable metal
      fraction, was the most toxic, ageing under in situ natural conditions seemingly
      contributed to attenuate LA soil risk. As a whole, combining multi-endpoint
      bioassays with scenario-targeted analysis (including leaching and ageing)
      provides reliable risk assessment in soils posing unacceptable environmental risk
      according to SVs, which is useful to optimise the required intervention measures.

PMID- 25940476
TI  - Levels, spatial distribution, and exposure risks of decabromodiphenylethane in
      soils of North China.
AB  - Eighty-seven soil samples collected from North China were analyzed for
      decabromodiphenyl ethane (DBDPE). The concentrations of DBDPE ranged from
      undetectable to 1612 ng/g, with the highest concentration present in Shandong.
      Additionally, the mean concentration of DBDPE in Shandong was found to be onefold
      higher than those found in Hebei and Shanxi, likely due to DBDPE production in
      Shandong. Relatively high concentrations of DBDPE in soils were also present in
      the south of Tianjin, where e-waste recycling may provide a source in this
      region. The fractions of DBDPE [DBDPE/(DBDPE + BDE209)] were lower than 0.5 in
      most soil samples, in agreement with the fact that deca-BDE is currently the main
      additive in brominated flame retardants (BFR) used in China. An obvious
      decreasing trend in DBDPE concentrations from east to west in North China was
      noted, with relatively higher DBDPE concentrations present in Shandong. A soil
      ingestion exposure assessment showed that for most sites, soil ingestion EDI was
      slightly lower than inhalation EDI; exceptions were found in several polluted
      sites, where soil ingestion was a more significant exposure route. 

PMID- 25940477
TI  - Review of PCBs in US schools: a brief history, an estimate of the number of
      impacted schools, and an approach for evaluating indoor air samples.
AB  - PCBs in building materials such as caulks and sealants are a largely unrecognized
      source of contamination in the building environment. Schools are of particular
      interest, as the period of extensive school construction (about 1950 to 1980)
      coincides with the time of greatest use of PCBs as plasticizers in building
      materials. In the USA, we estimate that the number of schools with PCB in
      building caulk ranges from 12,960 to 25,920 based upon the number of schools
      built in the time of PCB use and the proportion of buildings found to contain PCB
      caulk and sealants. Field and laboratory studies have demonstrated that PCBs from
      both interior and exterior caulking can be the source of elevated PCB air
      concentrations in these buildings, at levels that exceed health-based PCB
      exposure guidelines for building occupants. Air sampling in buildings containing
      PCB caulk has shown that the airborne PCB concentrations can be highly variable,
      even in repeat samples collected within a room. Sampling and data analysis
      strategies that recognize this variability can provide the basis for informed
      decision making about compliance with health-based exposure limits, even in cases
      where small numbers of samples are taken. The health risks posed by PCB
      exposures, particularly among children, mandate precautionary approaches to
      managing PCBs in building materials. 

PMID- 25940478
TI  - Effect of concentration gradients on biodegradation in bench-scale sand columns
      with HYDRUS modeling of hydrocarbon transport and degradation.
AB  - The present research investigated to what extent results obtained in small
      microcosm experiments can be extrapolated to larger settings with non-uniform
      concentrations. Microbial hydrocarbon degradation in sandy sediments was compared
      for column experiments versus homogenized microcosms with varying concentrations
      of diesel, Syntroleum, and fish biodiesel as contaminants. Syntroleum and fish
      biodiesel had higher degradation rates than diesel fuel. Microcosms showed
      significantly higher overall hydrocarbon mineralization percentages (p < 0.006)
      than columns. Oxygen levels and moisture content were likely not responsible for
      that difference, which could, however, be explained by a strong gradient of fuel
      and nutrient concentrations through the column. The mineralization percentage in
      the columns was similar to small-scale microcosms at high fuel concentrations.
      While absolute hydrocarbon degradation increased, mineralization percentages
      decreased with increasing fuel concentration which was corroborated by saturation
      kinetics; the absolute CO2 production reached a steady plateau value at high
      substrate concentrations. Numerical modeling using HYDRUS 2D/3D simulated the
      transport and degradation of the investigated fuels in vadose zone conditions
      similar to those in laboratory column experiments. The numerical model was used
      to evaluate the impact of different degradation rate constants from microcosm
      versus column experiments. 

PMID- 25940479
TI  - Direct gas-solid carbonation of serpentinite residues in the absence and presence
      of water vapor: a feasibility study for carbon dioxide sequestration.
AB  - Mineral carbonation of serpentinite mining residue offers an environmentally
      secure and permanent storage of carbon dioxide. The strategy of using readily
      available mining residue for the direct treatment of flue gas could improve the
      energy demand and economics of CO2 sequestration by avoiding the mineral
      extraction and separate CO2 capture steps. The present is a laboratory scale
      study to assess the possibility of CO2 fixation in serpentinite mining residues
      via direct gas-solid reaction. The degree of carbonation is measured both in the
      absence and presence of water vapor in a batch reactor. The gas used is a
      simulated gas mixture reproducing an average cement flue gas CO2 composition of
      18 vol.% CO2. The reaction parameters considered are temperature, total gas
      pressure, time, and concentration of water vapor. In the absence of water vapor,
      the gas-solid carbonation of serpentinite mining residues is negligible, but the
      residues removed CO2 from the feed gas possibly due to reversible adsorption. The
      presence of small amount of water vapor enhances the gas-solid carbonation, but
      the measured rates are too low for practical application. The maximum CO2
      fixation obtained is 0.07 g CO2 when reacting 1 g of residue at 200  degrees C
      and 25 barg (pCO2 ~ 4.7) in a gas mixture containing 18 vol.% CO2 and 10 vol.%
      water vapor in 1 h. The fixation is likely surface limited and restricted due to
      poor gas-solid interaction. It was identified that both the relative humidity and
      carbon dioxide-water vapor ratio have a role in CO2 fixation regardless of the
      percentage of water vapor. 

PMID- 25940480
TI  - Assessing the ecotoxicity of metal nano-oxides with potential for wastewater
      treatment.
AB  - The rapid development of nanotechnology and the increasing use of nanomaterials
      (NMs) raise concern about their fate and potential effects in the environment,
      especially for those that could be used for remediation purposes and that will be
      intentionally released to the environment. Despite the remarkable emerging
      literature addressing the biological effects of NMs to aquatic organisms, the
      existing information is still scarce and contradictory. Therefore, aimed at
      selecting NMs for the treatment of organic and inorganic effluents, we assessed
      the potential toxicity of NiO (100 and 10-20 nm), Fe2O3 (~85 * 425 nm), and TiO2
      (<25 nm), to a battery of aquatic organisms: Vibrio fischeri, Raphidocelis
      subcapitata, Lemna minor, Daphnia magna, Brachionus plicatilis, and Artemia
      salina. Also a mutagenic test was performed with two Salmonella typhimurium
      strains. Suspensions of each NM, prepared with the different test media, were
      characterized by dynamic light scattering (DLS) and eletrophoretic light
      scattering (ELS). For the assays with marine species, no toxicity was observed
      for all the compounds. In opposite, statistically significant effects were
      produced on all freshwater species, being D. magna the most sensitive organism.
      Based on the results of this study, the tested NMs can be classified in a
      decreasing order of toxicity NiO (100 nm) > NiO (10-20 nm) > TiO2 (<25 nm) >
      Fe2O3, allowing to infer that apparently Fe2O3 NMs seems to be the one with less
      risks for receiving aquatic systems. 

PMID- 25940481
TI  - Microbial community structure in a dual chamber microbial fuel cell fed with
      brewery waste for azo dye degradation and electricity generation.
AB  - The expansion in knowledge of the microbial community structure can play a vital
      role in the electrochemical features and operation of microbial fuel cells
      (MFCs). In this study, bacterial community composition in a dual chamber MFC fed
      with brewery waste was investigated for simultaneous electricity generation and
      azo dye degradation. A stable voltage was generated with a maximum power density
      of 305 and 269 mW m(-2) for brewery waste alone (2000 mg L(-1)) and after the azo
      dye (200 mg L(-1)) addition, respectively. Azo dye degradation was confirmed by
      Fourier transform infrared spectroscopy (FT-IR) as peak corresponding to -N=N-
      (azo) bond disappeared in the dye metabolites. Microbial communities attached to
      the anode were analyzed by high-throughput 454 pyrosequencing of the 16S rRNA
      gene. Microbial community composition analysis revealed that Proteobacteria (67.3
      %), Betaproteobacteria (30.8 %), and Desulfovibrio (18.3 %) were the most
      dominant communities at phylum, class, and genus level, respectively. Among the
      classified genera, Desulfovibrio most likely plays a major role in electron
      transfer to the anode since its outer membrane contains c-type cytochromes. At
      the genus level, 62.3 % of all sequences belonged to the unclassified category
      indicating a high level of diversity of microbial groups in MFCs fed with brewery
      waste and azo dye. HIGHLIGHTS: * Azo dye degradation and stable bioelectricity
      generation was achieved in the MFC. * Anodic biofilm was analyzed by high
      throughput pyrosequencing of the 16S rRNA gene. * Desulfovibrio (18.3 %) was the
      dominant genus in the classified genera. * Of the genus, 62.3 % were
      unclassified, thereby indicating highly diverse microbes. Graphical Abstract A
      schematic diagram of a dual chamber microbial fuel cell for azo dye degradation
      and current generation (with microbial communities at anode electrode).

PMID- 25940482
TI  - Production and optimization of biodiesel using mixed immobilized biocatalysts in
      packed bed reactor.
AB  - Vegetable oils are used as raw materials for biodiesel production using
      transesterification reaction. Several methods for the production of biodiesel
      were developed using chemical (alkali and acidic compounds) and biological
      catalysts (lipases). Biodiesel production catalyzed by lipases is energy and cost
      saving processes and is carried out at normal temperature and pressure. The need
      for an efficient method for screening larger number of variables has led to the
      adoption of statistical experimental design. In the present study, packed bed
      reactor was designed to study with mixed immobilized biocatalysts to have higher
      productivity under optimum conditions. Contrary to the single-step acyl migration
      mechanism, a two-step stepwise reaction mechanism involving immobilized Candida
      rugosa lipase and immobilized Rhizopus oryzae cells was employed for the present
      work. This method was chosen because enzymatic hydrolysis followed by
      esterification can tolerate high free fatty acid containing oils. The effects of
      flow rate and bed height on biodiesel yield were studied using two factors five
      level central composite design (CCD) and response surface methodology (RSM).
      Maximum biodiesel yield of 85 and 81 % was obtained for jatropha oil and karanja
      oil with the optimum bed height and optimum flow rate of 32.6 cm and 1.35 L/h,
      and 32.6 cm and 1.36 L/h, respectively. 

PMID- 25940484
TI  - Physical distribution of Ni, Pb and Zn in reclaimed mine soils observed by FE-SEM
      with an EDS detector.
AB  - The aim of this study was to physically demonstrate the associations between Ni,
      Pb and Zn and the different soil components. To achieve this, several soil
      samples were observed by field emission-scanning electron microscope (FE-SEM)
      equipped with an energy dispersive spectrometer (EDS) detector. The samples came
      from mine sites vegetated and/or amended with wastes (sewage sludges and paper
      mill residues). The concentrations of metals in the different soil fractions were
      quantified by a chemical sequential extraction in a previous study. The sorption
      capacity of the soils was evaluated with sorption experiments using the batch
      method. We corroborated the results obtained by the sequential extraction of
      metals as well as the sorption experiments with the observations from the FE-SEM
      with the EDS. We physically observed the associations between Ni, Pb and Zn and
      oxides, organic matter and clays. We also observed PbCaCO3 crystals in one of the
      soils, presumably formed during the sorption experiment. As it is not possible to
      know with complete certainty how Pb was retained by calcium in this soil by only
      using chemical methods, the use of microscopic techniques is crucial to ascertain
      how metals are associated with the different soil fractions. 

PMID- 25940483
TI  - A multibiomarker evaluation of urban, industrial, and agricultural exposure of
      small characins in a large freshwater basin in southern Brazil.
AB  - Iguacu River is the second most polluted river of Brazil. It receives
      agrochemicals and contaminants of urban and industrial sources along its course.
      A multibiomarker approach was employed here to evaluate the health of a small
      characin (Astyanax spp.) at two sites along the river, sampled during a dry
      (autumn) and a rainy (spring) season. Biomarkers were condition factor and
      somatic indices (gonads and liver); genetic damage (comet assay and micronucleus
      test); enzyme activities such as hepatic catalase (CAT) and glutathione S
      transferase (GST), lipoperoxidation (LPO), branchial and renal carbonic anhydrase
      (CA), acetylcholinesterase (AChE) in the muscle and the brain, histopathology of
      the liver and gills, and concentrations of polycyclic aromatic hydrocarbons
      (PAHs) in bile. There were no consistent differences in biomarker responses
      between the two study sites. Some biomarkers revealed greater potential impact in
      the rainy season, when increased amounts of contaminants are washed into the
      river (combined CAT inhibition and LPO increase, CA upregulation). Other
      biomarkers, however, revealed potential greater impact in the dry season, when
      contaminants potentially concentrate (GST induction, AChE inhibition, and liver
      histopathological alterations). Although of a complex nature, field experiments
      such as this provide rich data for monitoring protocols and assessment of general
      risk of exposure to pollutants of river systems. 

PMID- 25940485
TI  - Preliminary evaluation of Diopatra neapolitana regenerative capacity as a
      biomarker for paracetamol exposure.
AB  - An increasing number of studies established unequivocal relationships between
      exposure to pharmaceutical drugs and toxicity in wildlife. However, few studies
      investigated physiological alterations caused by such compounds in polychaetes.
      Thus, in this study, the effects of increasing concentrations of paracetamol were
      studied in the polychaete Diopatra neapolitana using tissue regenerative capacity
      as a biomarker. The obtained results revealed that individuals exposed to
      ecologically relevant concentrations (namely, 25 MUg/L) of paracetamol exhibited
      significantly lower capacity to regenerate their body in comparison with control
      organisms. This study evidenced that paracetamol can induce significant
      physiological alterations in D. neapolitana resulting in an overall diminished
      regenerative capacity, which is of significance to a species with high ecological
      and economic relevance. Additionally, this study indicates the promise of D.
      neapolitana as a test organism in laboratory-based bioassays, but also as an
      adequate sentinel species to pharmaceutical drugs. 

PMID- 25940486
TI  - Classification and identification of pigmented cocci bacteria relevant to the
      soil environment via Raman spectroscopy.
AB  - A soil habitat consists of a significant number of bacteria that cannot be
      cultivated by conventional means, thereby posing obvious difficulties in their
      classification and identification. This difficulty necessitates the need for
      advanced techniques wherein a well-compiled biomolecular database consisting of
      the already cultivable bacteria can be used as a reference in an attempt to link
      the noncultivable bacteria to their closest phylogenetic groups. Raman
      spectroscopy has been successfully applied to taxonomic studies of many systems
      like bacteria, fungi, and plants relying on spectral differences contributed by
      the variation in their overall biomolecular composition. However, these spectral
      differences can be obscured due to Raman signatures from photosensitive microbial
      pigments like carotenoids that show enormous variation in signal intensity
      hindering taxonomic investigations. In this study, we have applied laser-induced
      photobleaching to expel the carotenoid signatures from pigmented cocci bacteria.
      Using this method, we have investigated 12 species of pigmented bacteria abundant
      in soil habitats belonging to three genera mainly Micrococcus, Deinococcus, and
      Kocuria based on their Raman spectra with the assistance of a chemometric tool
      known as the radial kernel support vector machine (SVM). Our results demonstrate
      the potential of Raman spectroscopy as a minimally invasive taxonomic tool to
      identify pigmented cocci soil bacteria at a single-cell level. 

PMID- 25940487
TI  - Application of vertical flow constructed wetland in treatment of heavy metals
      from pulp and paper industry wastewater.
AB  - The paper production is material intensive and generates enormous quantity of
      wastewater containing organic pollutants and heavy metals. Present study
      demonstrates the feasibility of constructed wetlands (CWs) to treat the heavy
      metals from pulp and paper industry effluent by using vertical flow constructed
      wetlands planted with commonly available macrophytes such as Typha angustifolia,
      Erianthus arundinaceus, and Phragmites australis. Results indicate that the
      removal efficiencies of the planted CWs for iron, copper, manganese, zinc,
      nickel, and cadmium were 74, 80, 60, 70, 71, and 70 %, respectively. On the other
      hand, the removal efficiency of the unplanted system was significantly lower
      ranging between 31 and 55 %. Among the macrophytes, T. angustifolia and E.
      arundinaceus exhibited comparatively higher bioconcentration factor (10(2) to
      10(3)) than P. australis. 

PMID- 25940488
TI  - Phytoremediation of cadmium improved with the high production of endogenous
      phenolics and free proline contents in Parthenium hysterophorus plant treated
      exogenously with plant growth regulator and chelating agent.
AB  - Pot experiments were conducted to evaluate the effects of gibberellic acid (GA3)
      and ethylenediaminetetraacetic acid (EDTA) on growth parameters, cadmium (Cd)
      phytoextraction, total phenolics, free proline and chlorophyll content of
      Parthenium hysterophorus plant grown in Cd-contaminated (100 mg/kg) soil. GA3 was
      applied as foliar spray (10(-2), 10(-4) and 10(-6) M) while EDTA (40 mg/kg soil)
      was added to soil as single and in split doses. Results showed decrease in growth
      parameters due to Cd stress but P. hysterophorus plant demonstrated Cd
      hyperaccumulator potential based on bioconcentration factor (BCF). Lower
      concentration of GA3 (10(-6) M) showed highest significant increase in the growth
      parameters while Cd concentration, accumulation (1.97 +/- 0.11 mg/DBM) and
      bioconcentration (9.75 +/- 0.34) was significantly higher in the treatment T11
      (GA3 10(-2) + split doses of EDTA). Cadmium significantly increased the root free
      proline while total phenolic concentration was significantly high in all parts of
      the plant. Chlorophyll contents were significantly reduced by Cd. GA3 showed
      significant increase in phenolic and chlorophyll contents in plant. Cadmium
      accumulation in plant tissues showed positive correlation with free proline (R
      (2) = 0.527, R (2) = 0.630) and total phenolics (R (2) = 0.554, R (2) = 0.723) in
      roots and leaves, respectively. Cd contents negatively correlated with biomass,
      chlorophyll and total water contents. Proline and phenolic contents showed
      positive correlation with dry biomass of plant. These findings suggest further
      investigation to study the role of endogenous phenolics and proline in heavy
      metal phytoremediation. 

PMID- 25940489
TI  - Temporal variations of PM1 major components in an urban street canyon.
AB  - Seasonal changes in the levels of PM1 and its main components (organic carbon
      (OC), elemental carbon (EC), SO4 (2-), NO3 (-) and NH4 (+)) were studied in an
      urban street canyon in southeastern Spain. Although PM1 levels did not show an
      evident seasonal cycle, strong variations in the concentrations of its major
      components were observed. Ammonium sulfate, the main secondary inorganic
      compound, was found to be of regional origin. Its formation was favored during
      summer due to increased photochemical activity. In contrast, the concentrations
      of particulate ammonium nitrate, which is thermally unstable, were highest in
      winter. Although traffic emissions are the dominant source of EC in the city,
      variations in traffic intensity could not explain the seasonal cycle of this
      component. The higher EC concentrations during the cold months were attributed to
      the lower dispersion conditions and the increase in EC emissions. Special
      attention has been given to variations in organic carbon levels since it
      accounted for about one third of the total PM1 mass. The concentrations of both
      total OC and secondary OC (SOC) were maxima in winter. The observed seasonal
      variation in SOC levels is similar to that found in other southern European
      cities where the frequency of sunny days in winter is high enough to promote
      photochemical processes. 

PMID- 25940490
TI  - Spatial and seasonal variations of atmospheric particulate carbon fractions and
      identification of secondary sources at urban sites in North India.
AB  - An intensive measurement campaign was undertaken to characterize eight fractions
      of organic carbon (OC) and elemental carbon (EC) in particulate matter (PM) at
      four urban sites with different pollution characteristics during summer, post
      monsoon, and winter at Kanpur, India. Speciation samplers were used to collect
      particulate samples on quartz filters followed by analysis of OC and EC using
      Interagency Monitoring of Protected Visual Environments (IMPROVE)-based
      thermal/optical reflectance (TOR) method. Based on 24-h average results at each
      site, the highest levels of OC and EC were observed during winter as 96.7 +/-
      26.9 and 31.8 +/- 9.8 MUg/m(3) at residential site and traffic site,
      respectively. The levels of OC at residential sites during winter appeared to be
      more than twice of that during summer. The site close to the road traffic had the
      least value of OC/EC, as 1.77 +/- 0.28 during post-monsoon, and the site
      influenced by emissions of domestic cooking and heating had the highest value of
      OC/EC, as 4.05 +/- 0.79 during winter. The average abundances of OC1, OC2, OC3,
      OC4, OP, EC1, EC2, and EC3 in total carbon (TC) at all sites for three seasons
      were 10.03, 19.04, 20.03, 12.32, 10.53, 33.39, 3.21, and 1.99 %, respectively. A
      sharp increase in levels of OC1 and EC1-OP during winter at two residential sites
      revealed that biomass burning could be a significant contributor to carbonaceous
      aerosols. From the application of EC-tracer method, it was observed that
      contribution of secondary organic carbon (SOC) to PM mass increased from 5 %
      during post-monsoon to 16 % during winter at residential sites and from 2 %
      during post-monsoon to 7 % during winter at traffic sites. Therefore, it could be
      inferred that increase in primary emissions coupled with unfavorable
      meteorological conditions could cause particle agglomeration and hygroscopic
      growth, leading to unpleasant pollution episode during winter. 

PMID- 25940491
TI  - Characterization and performance evaluation of an innovative mesoporous activated
      carbon used for drinking water purification in comparison with commercial
      carbons.
AB  - The preparation, characterization, and performance evaluation of an innovative
      mesoporous activated carbon (C-XHIT) were conducted in this study. Comparative
      evaluation with commercial carbons (C-PS and C-ZJ15) and long-term performance
      evaluation of C-XHIT were conducted in small-scale system-A (S-A) and pilot-scale
      system-B (S-B-1 and S-B-2 in series), respectively, for treating water from
      Songhua River. The cumulative uptake of micropollutants varied with KBV (water
      volume fed to columns divided by the mass of carbons, m(3) H2O/kg carbon) was
      employed in the performance evaluation. The results identified that mesoporous
      and microporous volumes were simultaneously well-developed in C-XHIT. Higher
      mesoporosity (63.94 %) and average pore width (37.91 A) of C-XHIT ensured a
      higher adsorption capacity for humic acid compared to C-PS and C-ZJ15. When the
      KBV of S-A reached 12.58 m(3) H2O/kg carbon, cumulative uptake of organic
      pollutants achieved by C-XHIT increased by 32.82 and 156.29 % for DOC (QC) and
      22.53 and 112.48 % for UV254 (QUV) compared to C-PS and C-ZJ15, respectively; in
      contrast, the adsorption capacity of NH4 (+)-N did not improve significantly. C
      XHIT achieved high average removal efficiencies for DOC (77.43 +/- 16.54 %) and
      UV254 (83.18 +/- 13.88 %) in S-B over 253 days of operation (KBV = 62 m(3) H2O/kg
      carbon). Adsorption dominated the removal of DOC and UV254 in the initial phases
      of KBV (0-15 m(3) H2O/kg carbon), and simultaneous biodegradation and adsorption
      were identified as the mechanisms for organic pollutant uptake at KBV above 25
      m(3) H2O/kg carbon. The average rates contributed by S-B-1 and S-B-2 for QC and
      QUV were approximately 0.75 and 0.25, respectively. Good linear and exponential
      correlations were observed between S-A and S-B in terms of QC and QUV obtained by
      C-XHIT, respectively, for the same KBV ranges, indicating a rapid and cost-saving
      evaluation method. The linear correlation between mesoporosity and QC (QUV) was
      also identified by the evolution of the property indices of C-XHIT. 

PMID- 25940492
TI  - Relationships between stability, maturity, water-extractable organic matter of
      municipal sewage sludge composts and soil functionality.
AB  - Compost capability of restoring or enhancing soil quality depends on several
      parameters, such as soil characteristics, compost carbon, nitrogen and other
      nutrient content, heavy metal occurrence, stability and maturity. This study
      investigated the possibility of relating compost stability and maturity to water
      extractable organic matter (WEOM) properties and amendment effect on soil
      quality. Three composts from municipal sewage sludge and rice husk (AN, from
      anaerobic wastewater treatment plants; AE, from aerobic ones; MIX, from both
      anaerobic and aerobic ones) have been analysed and compared to a traditional
      green waste compost (GM, from green manure, solid waste and urban sewage sludge).
      To this aim, WEOMs were characterized through chemical analysis; furthermore,
      compost stability was evaluated through oxygen uptake rate calculation and
      maturity was estimated through germination index determination, whereas compost
      impact on soil fertility was studied, in a lab-scale experiment, through
      indicators as inorganic nitrogen release, soil microbial biomass carbon, basal
      respiration rate and fluorescein di-acetate hydrolysis. The obtained results
      indicated that WEOM characterization could be useful to investigate compost
      stability (which is related to protein and phenol concentrations) and maturity
      (related to nitrate/ammonium ratio and degree of aromaticity) and then compost
      impact on soil functionality. Indeed, compost stability resulted inversely
      related to soil microbial biomass, basal respiration rate and fluorescein di
      acetate hydrolysis when the products were applied to the soil. 

PMID- 25940493
TI  - Binding intensity and metal partitioning in soils affected by mining and smelting
      activities in Minas Gerais, Brazil.
AB  - Mining and smelting activities are potential sources of heavy metal
      contamination, which pose a threat to human health and ecological systems. This
      study investigated single and sequential extractions of Zn, Pb, and Cd in
      Brazilian soils affected by mining and smelting activities. Soils from a Zn
      mining area (soils A, B, C, D, E, and the control soil) and a tailing from a
      smelting area were collected in Minas Gerais state, Brazil. The samples were
      subjected to single (using Mehlich I solution) and sequential extractions. The
      risk assessment code (RAC), the redistribution index (U ts ), and the reduced
      partition index (I R ) have been applied to the sequential extraction data. Zinc
      and Cd, in soil samples from the mining area, were found mainly associated with
      carbonate forms. This same pattern did not occur for Pb. Moreover, the Fe-Mn
      oxides and residual fractions had important contributions for Zn and Pb in those
      soils. For the tailing, more than 70 % of Zn and Cd were released in the
      exchangeable fraction, showing a much higher mobility and availability of these
      metals at this site, which was also supported by results of RAC and I R . These
      differences in terms of mobility might be due to different chemical forms of the
      metals in the two sites, which are attributable to natural occurrence as well as
      ore processing. 

PMID- 25940494
TI  - Tributyltin--critical pollutant in whole water samples--development of traceable
      measurement methods for monitoring under the European Water Framework Directive
      (WFD) 2000/60/EC.
AB  - Tributyltin is listed as one of the priority substances in the European Water
      Framework Directive (WFD). Despite its decreasing input in the environment, it is
      still present and has to be monitored. In the European Metrology Research
      Programme project ENV08, a sensitive and reliable analytical method according to
      the WFD was developed to quantify this environmental pollutant at a very low
      limit of quantification. With the development of such a primary reference method
      for tributyltin, the project helped to improve the quality and comparability of
      monitoring data. An overview of project aims and potential analytical tools is
      given. 

PMID- 25940495
TI  - Geochemical fractions and risk assessment of trace elements in soils around
      Jiaojia gold mine in Shandong Province, China.
AB  - Soils located adjacent to the Jiaojia gold mine were sampled and analyzed to
      determine the degree of which they were contaminated by trace elements (Hg, As,
      Cd, Pb, Cu, and Zn) in Shandong Province, China. All 18 samples exhibited mean
      Hg, As, Cd, and Pb concentrations in excess of local background values, while the
      mean concentrations of Cu and Zn were below the background values. In addition,
      the concentrations of trace elements in gold smelter (GS) soils were higher than
      in the gold mine (GM) soils. The result from a modified Tessier sequential
      extraction procedure was that with the exception of Cu in soils near the smelter,
      the trace elements were predominantly associated with the residual fraction.
      After residual fraction, most Hg was mainly humic acid and strong organic
      fraction, while most As was the humic acid. Cd was associated with the water
      soluble, ion exchange, and carbonate fractions compared with the other trace
      elements. Furthermore, Cu, Pb, and Zn were more concentrated in the humic acid
      and Fe/Mn oxide fraction. The fractions of trace elements were affected by soil
      pH and Ec (Electrical conductivity). The humic acid fraction of Hg as well as the
      ion exchange fraction of Cd and Zn displayed negative correlations with soil pH.
      The strong organic fraction of Hg, the Fe/Mn oxide fraction of Cd, and the
      carbonate fraction of Zn were positively related to the soil Ec. The strong
      organic fraction and ion exchange fraction of Zn were negatively related to soil
      Ec. However, the ion exchange and carbonate fractions of As showed significant
      positive correlations with soil pH. A calculated individual availability factor
      (A f (i) ) is used; the values of each trace element in the soils are in the
      following order: Cu > Cd > Pb > Zn > As > Hg. When combined with a risk
      assessment code, data suggest that Hg, As, Pb, and Zn levels showed low risk for
      the environment, whereas Cd levels in soils adjacent to the GM and Cu levels in
      soils adjacent to the GS showed medium risk to the environment, and Cd levels in
      soils adjacent to the GS exhibited higher environment risk. 

PMID- 25940497
TI  - Heavy metal removal from acid mine drainage by calcined eggshell and microalgae
      hybrid system.
AB  - This study investigates the use of calcined eggshells and microalgae for the
      removal of heavy metals from acid mine drainage (AMD) and the simultaneous
      enhancement of biomass productivity. The experiment was conducted over a period
      of 6 days in a hybrid system containing calcined eggshells and the microalgae
      Chlorella vulgaris. The results show that the biomass productivity increased to
      ~8.04 times its initial concentration of 0.367 g/L as measured by an optical
      panel photobioreactor (OPPBR) and had a light transmittance of 95 % at a depth of
      305 mm. On the other hand, the simultaneous percent removal of Fe, Cu, Zn, Mn,
      As, and Cd from the AMD effluent was found to be 99.47 to 100 %. These results
      indicate that the hybrid system with calcined eggshells and microalgae was highly
      effective for heavy metal removal in the AMD. 

PMID- 25940496
TI  - Chlordecone exposure and adverse effects in French West Indies populations.
AB  - Chlordecone (Kepone) is an organochlorine insecticide that has been used as
      insecticide and fungicide. In the French West Indies, Guadeloupe and Martinique,
      it was intensively applied to banana fields from 1973 to 1993 to control root
      borers. This pesticide undergoes no significant biotic or abiotic degradation in
      the environment and is still present in soils where it was applied. It was only
      in 1999 that health and environmental authorities became aware of the extent of
      the chlordecone pollution of environmental media, including soils, waterways, and
      the food chain. Earlier observations and toxicological studies have demonstrated
      that chlordecone is a reproductive and developmental toxicant, neurotoxic and
      carcinogenic in rodents, and is an endocrine-disrupting chemical because of its
      estrogenic properties both in vitro and in vivo. Several surveys have confirmed
      that the French West Indian population continues to be exposed to this chemical
      though consumption of contaminated foodstuffs. Here, we report the findings of
      various epidemiological studies conducted in the French West Indies to assess the
      impact of environmental exposure to chlordecone on the health of the population. 

PMID- 25940498
TI  - Direct flexor carpi radialis to abductor pollicis longus tenodesis: an
      alternative technique for ligament suspension following trapeziectomy.

PMID- 25940499
TI  - Tensile mechanical properties of human forearm tendons.
AB  - Previous studies of the mechanical properties of tendons in the upper limb have
      used embalmed specimens or sub-optimal methods of measurement. The aim of this
      study was to determine the biomechanical properties of all tendons from five
      fresh frozen cadaveric forearms using updated methodology. The cross-sectional
      area of tendons was accurately measured using a laser reflectance system. Tensile
      testing was done in a precision servo-hydraulic device with cryo-clamp fixation.
      We determined that the cross-sectional area of some tendons is variable and
      directly influences the calculated material properties; visual estimation of this
      is unreliable. Data trends illustrate that digital extensor tendons possess the
      greatest tensile strength and a higher Young's modulus than other tendon types. 

PMID- 25940500
TI  - Effect of volar angulation of extra-articular distal radius fractures on distal
      radioulnar joint stability: a biomechanical study.
AB  - The relationship between increased volar tilt of the distal radius and distal
      radioulnar joint stability was examined. Distal radioulnar joint stiffness was
      recorded at 10 degrees  intervals from 10 degrees  dorsal angulation to 20
      degrees  of volar angulation from the anatomical position of the radius. Tests
      were performed with the intact radioulnar ligament and repeated after partial and
      then complete sectioning of the radioulnar ligament at the ulnar fovea. With the
      intact radioulnar ligament, distal radioulnar joint stiffness increased
      significantly at 10 degrees  and 20 degrees  of volar angulation. Partial
      sectioning of the radioulnar ligament resulted in an approximate 10% decrease of
      distal radioulnar joint stiffness compared with the intact state, but distal
      radioulnar joint stiffness still increased significantly with greater volar tilt.
      Complete sectioning of the radioulnar ligament significantly decreased distal
      radioulnar joint stiffness, and increasing the volar tilt did not result in
      increased distal radioulnar joint stiffness. These results suggest that volar
      angulation deformities of the distal radius should be corrected to 10 degrees  of
      volar tilt when the triangular fibrocartilage complex is intact. Level of
      evidence: N/A.

PMID- 25940501
TI  - Activation treatment of recipient oocytes affects the subsequent development and
      ploidy of bovine parthenogenetic and somatic cell nuclear transfer (SCNT)
      embryos.
AB  - We evaluated the potential effect of anisomycin, an antibiotic produced by
      Streptomyces griseolus, on the parthenogenetic activation of bovine oocytes and
      reconstructed somatic-cell nuclear transfer (SCNT) embryos. A higher cleavage and
      blastocyst rate were achieved with anisomycin (70.3% and 27.8%) and 6
      dimethylaminopurine (DMAP) (73.3% and 30.2%), relative to oocytes
      parthenogenetically activated with cycloheximide (CHX) (54.1% and 20.2%). In
      reconstructed SCNT embryos, a greater proportion of embryos reached the
      blastocyst stage after anisomycin (32.2%) compared to DMAP (22.3%) and CHX
      (23.5%) treatment. Furthermore, the quality of embryos-assessed by the total
      number of cells and the inner cell mass-to-total-cell ratio-was higher with
      anisomycin (166.2 +/- 6.9 and 26.9 +/- 1.9) compared to DMAP (135.0 +/- 8.7 and
      39.4 +/- 3.5) and CHX (149.1 +/- 8.4 and 36.3 +/- 2.5), while a lower percentage
      of chromosomal abnormalities was observed with anisomycin compared to DMAP and
      CHX treatments, both in parthenotes (though not significant) and in SCNT embryos
      (P < 0.05). Therefore, anisomycin can enhance the in vitro developmental
      potential in parthenotes and reconstructed SCNT embryos, specifically improving
      the quality of SCNT embryos and decreasing the abnormal ploidy of parthenotes and
      SCNT embryos compared to the traditional protocols of chemical activation with
      DMAP and CHX. These results may have important implications for the success of
      reproductive technologies, including SCNT and intracytoplasmic sperm injection,
      in different mammalian species.

PMID- 25940502
TI  - Stevens-Johnson syndrome: Old and new opportunities for prevention.

PMID- 25940503
TI  - Novel equine conceptus?endometrial interactions on Day 16 of pregnancy based on
      RNA sequencing.
AB  - Maintenance of pregnancy is dependent on the exchange of signals between the
      conceptus and the endometrium. The objective of this study was to use next
      generation sequencing to determine transcriptome blueprints of the conceptus and
      endometrium 16 days after ovulation in the horse. There were 7760 and 10 182
      genes expressed in the conceptus and endometrium, respectively, of which 7029
      were present in both. Genes related to developmental processes were enriched
      among conceptus-specific transcripts, whereas many endometrium-specific genes had
      known roles in cell communication, cell adhesion and response to stimuli. The
      integrin signalling pathway was overrepresented in both transcriptomes. In that
      regard, it was hypothesised that integrins ITGA5B1 and ITGAVB3 interact with
      conceptus-derived fibrinogen, potentially contributing to cessation of conceptus
      mobility. That several growth factors and their corresponding receptors (e.g.
      HDGF, NOV, CYR61, CTGF, HBEGF) were expressed by conceptus and endometrium were
      attributed to cross-talk. In addition, Cytoscape interaction analysis revealed a
      plethora of interactions between genes expressed by the conceptus and
      endometrium, during a period when the former had substantial movement within the
      uterus. This is the first report of concurrent transcriptome analysis of
      conceptus and endometrium in the mare, with numerous findings to provide
      rationale for further investigation.

PMID- 25940504
TI  - Risk factors and prognostic scale for cytomegalovirus (CMV) infection in CMV
      seropositive patients after allogeneic hematopoietic cell transplantation.
AB  - AIM: We aimed to study the risk factors for first and subsequent cytomegalovirus
      (CMV) infection among patients who are CMV seropositive and underwent allogeneic
      hematopoietic cell transplantation (HCT). METHODS: We performed an historical
      cohort study of all sequential CMV-seropositive patients who underwent allogeneic
      HCT at a single center. Between May 2007 and December 2012, 121 patients
      fulfilled inclusion criteria. RESULTS: Multivariate model identified
      myeloablative preparative regimen (hazard ratio [HR] = 4.297, P = 0.033) and
      acute graft-versus-host disease (GVHD) prior to infection (HR = 5.091, P = 0.021)
      as risk factors for first CMV infection. The cumulative incidences of first CMV
      infection for patients with 0, 1, and 2 risk factors were 52%, 71%, and 91%,
      respectively. Multivariate analysis identified the diagnosis of lymphoma/myeloma
      (HR = 3.5, P = 0.049) and GVHD (HR = 1.280, P = 0.045) as risk factors for
      subsequent CMV infection. High graft CD3 stem cell dose was associated with a
      trend of lower rate of subsequent CMV infection (HR = 0.543, P = 0.056). The
      cumulative incidences for subsequent CMV infection in patients with 0, 1, and 2-3
      risk factors were 11%, 41%, and 77%, respectively. CONCLUSION: In conclusion, in
      CMV-seropositive patients, myeloablative conditioning and acute GVHD are risk
      factors for first CMV infection, while lymphoma/myeloma, ongoing GVHD, and low
      CD3 graft content are risk factors for subsequent infection.

PMID- 25940506
TI  - Neonatal nosocomial bloodstream infections at a referral hospital in a middle
      income country: burden, pathogens, antimicrobial resistance and mortality.
AB  - BACKGROUND: Data on nosocomial bloodstream infection (BSI) rates, pathogens,
      mortality and antimicrobial resistance in African neonates are limited. METHODS:
      Nosocomial neonatal BSI at Tygerberg Hospital, Cape Town were retrospectively
      reviewed between 1 January 2009 and 31 December 2013. Laboratory and hospital
      data were used to determine BSI rates, pathogen profile, mortality and
      antimicrobial resistance in selected nosocomial pathogens. RESULTS: Of 6521 blood
      cultures taken over 5 years, 1145 (17.6%) were culture-positive, and 717 (62.6%)
      discrete nosocomial BSI episodes were identified. Nosocomial BSI rates remained
      unchanged over time (overall 3.9/1000 patient days, 95% CI 3.6-4.2, chi(2) for
      trend P = 0.23). Contamination rates were relatively high (5.1%, 95% CI 4.6
      5.7%). Among BSI pathogens, Gram-negatives predominated (65% vs 31% Gram
      positives and 4% fungal); Klebsiella pneumoniae (235, 30%), Staphylococcus aureus
      (112, 14%) and Enterococci (88, 11%) were most prevalent. Overall crude BSI
      mortality was 16% (112/717); Gram-negative BSI was significantly associated with
      mortality (P = 0.007). Mortality occurred mostly in neonates of very low (33/112,
      29%) or extremely low (53/112, 47%) birthweight. Deaths attributed to nosocomial
      BSI declined significantly over time (chi(2) for trend P = 0.01). The prevalence
      of antibiotic-resistant pathogens was high: methicillin-resistant Staphylococcus
      aureus 66%, multidrug-resistant A. baumanni 90% and extended-spectrum beta
      lactamase-producing K. pneumoniae 73%. CONCLUSION: The burden of nosocomial
      neonatal BSI at this middle-income country referral neonatal unit is substantial
      and remained unchanged over the study period, although attributable mortality
      declined significantly. Nosocomial BSI pathogens exhibited high levels of
      antimicrobial resistance.

PMID- 25940507
TI  - Frey's Syndrome After Herpes Zoster Virus Infection in a 2-Year-Old Girl.
AB  - Frey's syndrome is characterized by sweating and flushing in the temporal and
      preauricular areas after a salivary stimulus. It is caused by damage to the
      auriculotemporal nerve, hence the alternative name of auriculotemporal syndrome.
      We report the case of a 2-year-old girl presenting with postprandial unilateral
      flushing that developed after a herpes zoster infection. 

PMID- 25940505
TI  - Chemokine (C-C motif) ligand 3 detection in the serum of persons exposed to
      asbestos: A patient-based study.
AB  - Exposure to asbestos results in serious risk of developing lung and mesothelial
      diseases. Currently, there are no biomarkers that can be used to diagnose
      asbestos exposure. The purpose of the present study was to determine whether the
      levels or detection rate of chemokine (C-C motif) ligand 3 (CCL3) in the serum
      are elevated in persons exposed to asbestos. The primary study group consisted of
      76 healthy subjects not exposed to asbestos and 172 healthy subjects possibly
      exposed to asbestos. The secondary study group consisted of 535 subjects possibly
      exposed to asbestos and diagnosed with pleural plaque (412), benign hydrothorax
      (10), asbestosis (86), lung cancer (17), and malignant mesothelioma (10). All
      study subjects who were possibly exposed to asbestos had a certificate of
      asbestos exposure issued by the Japanese Ministry of Health, Labour and Welfare.
      For the primary study group, levels of serum CCL3 did not differ between the two
      groups. However, the detection rate of CCL3 in the serum of healthy subjects
      possibly exposed to asbestos (30.2%) was significantly higher (P < 0.001) than
      for the control group (6.6%). The pleural plaque, benign hydrothorax, asbestosis,
      and lung cancer groups had serum CCL3 levels and detection rates similar to that
      of healthy subjects possibly exposed to asbestos. The CCL3 chemokine was detected
      in the serum of 9 of the 10 patients diagnosed with malignant mesothelioma. Three
      of the patients with malignant mesothelioma had exceptionally high CCL3 levels.
      Malignant mesothelioma cells from four biopsy cases and an autopsy case were
      positive for CCL3, possibly identifying the source of the CCL3 in the three
      malignant mesothelioma patients with exceptionally high serum CCL3 levels. In
      conclusion, a significantly higher percentage of healthy persons possibly exposed
      to asbestos had detectable levels of serum CCL3 compared to healthy unexposed
      control subjects. 

PMID- 25940508
TI  - Significance of Raised Flow Velocity in Basilar Artery in Patients with Acute
      Ischemic Stroke: Focal Stenosis, Coexistent Stenosis, and Collateral Flow.
AB  - BACKGROUND AND PURPOSE: Increased cerebral blood flow velocity of basilar artery
      (BA) is common but often neglected. By using digital subtraction angiography
      (DSA) to detect intracranial large artery stenosis, we performed transcranial
      Doppler (TCD) to evaluate cerebral hemodynamic changes of stroke patients.
      METHODS: Acute stroke patients with TCD-detected raised peak systolic velocity
      (PSV) in BA (>=100 cm/second) were recruited. RESULTS: Among 91 recruited
      patients, BA stenosis (>50%) was confirmed by using DSA in 29 patients (32%),
      among which 20 patients (70.0%) had coexistent internal carotid artery (ICA) and
      vertebral artery (VA) stenoses. Among patients without BA stenosis (n = 62, 68%),
      severe stenosis or occlusion of ICA was evaluated in 22 patients (22/62, 35.4%)
      and severe stenosis or occlusion of VA was detected in 22 patients (22/62,
      35.4%). Among the values of PSV (120, 140, 160, and 180 cm/second) and the
      stenotic-to-prestenotic ratio (SPR) (1.5, 2.0, 2.5, and 3.0), 160 cm/second was
      found to show the highest predictive value (area under the receiver operator
      characteristic curve: .75, 95% CI: .65-.86), with a sensitivity of .70 and a
      specificity of .81. CONCLUSIONS: Apart from an intrinsic BA stenosis, high-grade
      steno-occlusion of ICA or VA may contribute a lot to induce an elevated flow
      velocity in BA. A higher value of cutoff point may increase the accuracy of
      diagnosing BA stenosis.

PMID- 25940509
TI  - Re-evaluation of Pre-pump Arterial Pressure to Avoid Inadequate Dialysis and
      Hemolysis: Importance of Prepump Arterial Pressure Monitoring in Hemodialysis
      Patients.
AB  - Prepump arterial pressure (PreAP) is monitored to avoid generating excessive
      negative pressure. The National Kidney Foundation K/DOQI clinical practice
      guidelines for vascular access recommend that PreAP should not fall below -250 mm
      Hg because excessive negative PreAP can lead to a decrease in the delivery of
      blood flow, inadequate dialysis, and hemolysis. Nonetheless, these
      recommendations are consistently disregarded in clinical practice and pressure
      sensors are often removed from the dialysis circuit. Thus far, delivered blood
      flow has been reported to decrease at values more negative than -150 mm Hg of
      PreAP. These values have been analyzed by an ultrasonic flowmeter and not
      directly measured. Furthermore, no known group has evaluated whether PreAP
      induced hemolysis occurs at a particular threshold. Therefore, the aim of this
      study was to clarify the importance of PreAP in the prediction of inadequate
      dialysis and hemolysis. By using different diameter needles, human blood samples
      from healthy volunteers were circulated in a closed dialysis circuit. The
      relationship between PreAP and delivered blood flow or PreAP and hemolysis was
      investigated. We also investigated the optimal value for PreAP using several
      empirical monitoring methods, such as a pressure pillow. Our investigation
      indicated that PreAP is a critical factor in the determination of delivered blood
      flow and hemolysis, both of which occured at pressure values more negative than 
      150 mm Hg. With the exception of direct pressure monitoring, commonly used
      monitoring methods for PreAP were determined to be ineffective. We propose that
      the use of a vacuum monitor would permit regular measurement of PreAP. 

PMID- 25940510
TI  - Correction of Brassiere Strap Grooves with Fat Injections.
AB  - BACKGROUND: The size and weight of hypertrophied breast can cause both physical
      and psychological problems. Although the majority of these problems can be solved
      with breast reduction surgery, the particular problem of development of brassiere
      strap grooves on the shoulders due to the weight of the breasts cannot be
      corrected with this method. OBJECTIVES: Breast reduction surgery focuses only on
      the increased dimensions of breasts: fullness of the thoracic wall lateral to the
      breasts, as well as the appearance of brassiere strap grooves, need to be taken
      into consideration to obtain a better upper body image. Therefore, we present a
      series of 10 female patients who were treated with fat injections for the
      correction of brassiere strap grooves. METHODS: Reduction mammaplasty and fat
      injections into the brassiere strap grooves were performed during the same
      session. RESULTS: Dramatic changes are obtained with judicious placement of fat
      into the bra strap grooves. CONCLUSIONS: A more aesthetic and harmonious look can
      be obtained with using these combined aesthetic procedures in appropriately
      selected patients. LEVEL OF EVIDENCE: 4 Therapeautic.

PMID- 25940512
TI  - Residues 41V and/or 210D in the NP protein enhance polymerase activities and
      potential replication of novel influenza (H7N9) viruses at low temperature.
AB  - BACKGROUND: The influenza A (H7N9) virus emerged in the spring of 2013 in China.
      It contained six internal genes from Y280-like H9N2 viruses, which have co
      circulated with G1-like lineage viruses throughout poultry in China. Accompanied
      with continuous reassortment among H7N9 and H9N2 viruses in poultry, it is
      possible for H7N9 viruses to acquire internal genes of G1-lineage viruses. Thus,
      it is important to evaluate potential impact of G1-like viruses on the H7N9
      viruses. FINDINGS: We used in vitro assays of polymerase activities and growth
      kinetics to evaluate the potential contribution of G1-like virus genes to the
      replication abilities of H7N9 viruses. Two mutations in the NP protein (41V
      and/or 210D) could enhance H7N9 RNP activities, especially at low temperature (33
      degrees C, which is similar to the temperature of human upper respiratory tract).
      Meanwhile, G1 viruses with V41I or D210E substitutions exhibited poor growth
      ability in the early infection stage at low temperature. The D210E substitution
      also reduced the replication ability of G1 virus at 12 and 24 hour post infection
      at 37 degrees C. In both tested temperatures, V41I could compensate for the
      defective virus replication induced by the D210E mutation. CONCLUSIONS: Mutations
      41V and/or 210D in the NP protein conferred improved RNP activity in H7N9 viruses
      and promoted the replication ability of H9N2 viruses, particularly at lower
      temperature. Substitutions at these two positions may promote the replication
      ability of H7N9 viruses in low temperature and thus might contribute to viral
      transmissibility. While these two residues have not yet been observed in H7N9
      viruses, attention should be devoted to these two residues.

PMID- 25940511
TI  - The ticking clock of Cayo Santiago macaques and its implications for
      understanding human circadian rhythm disorders.
AB  - The circadian clock disorders in humans remain poorly understood. However, their
      impact on the development and progression of major human conditions, from cancer
      to insomnia, metabolic or mental illness becomes increasingly apparent.
      Addressing human circadian disorders in animal models is, in part, complicated by
      inverse temporal relationship between the core clock and specific physiological
      or behavioral processes in diurnal and nocturnal animals. Major advantages of a
      macaque model for translational circadian research, as a diurnal vertebrate
      phylogenetically close to humans, are further emphasized by the discovery of the
      first familial circadian disorder in non-human primates among the rhesus monkeys
      originating from Cayo Santiago. The remarkable similarity of their pathological
      phenotypes to human Delayed Sleep Phase Disorder (DSPD), high penetrance of the
      disorder within one branch of the colony and the large number of animals
      available provide outstanding opportunities for studying the mechanisms of
      circadian disorders, their impact on other pathological conditions, and for the
      development of novel and effective treatment strategies.

PMID- 25940513
TI  - Fluorescent In Situ Targeting Probes for Rapid Imaging of Ovarian-Cancer-Specific
      gamma-Glutamyltranspeptidase.
AB  - gamma-Glutamyltranspeptidase (GGT) is a tumor biomarker that selectively
      catalyzes the cleavage of glutamate overexpressed on the plasma membrane of tumor
      cells. Here, we developed two novel fluorescent in situ targeting (FIST) probes
      that specifically target GGT in tumor cells, which comprise 1) a GGT-specific
      substrate unit (GSH), and 2) a boron-dipyrromethene (BODIPY) moiety for
      fluorescent signalling. In the presence of GGT, sulfur-substituted BODIPY was
      converted to amino-substituted BODIPY, resulting in dramatic fluorescence
      variations. By exploiting this enzyme-triggered photophysical property, we
      employed these FIST probes to monitor the GGT activity in living cells, which
      showed remarkable differentiation between ovarian cancer cells and normal cells.
      These probes represent two first-generation chemodosimeters featuring enzyme
      mediated rapid, irreversible aromatic hydrocarbon transfer between the sulfur and
      nitrogen atoms accompanied by switching of photophysical properties.

PMID- 25940514
TI  - Childhood emotional abuse and borderline personality features: The role of
      anxiety sensitivity among adolescents.
AB  - Borderline personality disorder (BPD) is a pervasive personality disorder that
      poses a burden for affected individuals, their family members and society as a
      whole. Current research suggests that early childhood abuse, including emotional
      abuse, may be an important predictor of later BPD symptomology. Further, an
      emerging body of literature suggests that anxiety sensitivity (AS) may serve as a
      form of emotional vulnerability and be a key variable in the relation between
      abuse and the development of BPD symptomatology. This literature has relied on
      retrospective recall of abuse and AS in adult samples. As a result, there is a
      dearth of literature examining these variables in adolescence, which is a
      developmental period in which personality traits begin to emerge. This study
      explored the impact of AS in the development of BPD symptoms in a group of 277
      adolescents. Results suggest a significant indirect effect of emotional abuse on
      BPD symptoms via AS, after controlling for sex, grade and prior levels of AS
      (indirect effect = 0.04, standard error (SE) = 0.02 (95% confidence interval (CI)
      = 0.001-0.070)). These findings suggest that, among adolescents, AS may serve as
      an important contributor to the development of BPD symptoms. Implications for
      interventions and future research are further discussed.

PMID- 25940515
TI  - The lessons and legacy of the programme for dangerous and severe personality
      disorders.

PMID- 25940516
TI  - Autobiographical memory in borderline personality disorder-A systematic review.
AB  - Borderline personality disorder is a severe psychiatric illness. A key feature of
      the disorder is a disorganized sense of self often referred to as identity
      diffusion. Autobiographical memory is memory for personal life events. One of the
      main functions of these memories is to enable us to understand who we are by
      connecting past, present and future experiences. It seems that autobiographical
      memory is in some way disrupted in individuals with borderline personality
      disorder. A systematic review is conducted looking at studies that focus on the
      potential connections. We find that although a number of studies have been
      published results remain inconsistent. Furthermore, we find that many of the
      studies suffer from inadequate designs particularly regarding the reported
      measures of autobiographical memory. We discuss potential links between
      personality functioning, identity diffusion, autobiographical memory and
      borderline personality disorder.

PMID- 25940518
TI  - Influence of Thrombolysis and Mechanical Ventilation on Echocardiographic
      Predictors of Survival after Acute Pulmonary Embolism.

PMID- 25940517
TI  - Impact of CLAD Phenotype on Survival After Lung Retransplantation: A Multicenter
      Study.
AB  - Chronic lung allograft dysfunction (CLAD) remains a major problem after lung
      transplantation with no definitive treatment except redo lung transplantation (re
      LTx) in selected candidates. However, CLAD is not a homogeneous entity and
      different phenotypes exist. Therefore, we aimed to evaluate the effect of CLAD
      phenotypes on survival after re-LTx for CLAD. Patients who underwent re-LTx for
      respiratory failure secondary to CLAD in four LTx centers between 2003 and 2013
      were included in this retrospective analysis. Bronchiolitis obliterans syndrome
      (BOS) and restrictive CLAD (rCLAD) were distinguished using pulmonary function,
      radiology and explant lung histopathology. Patient variables pre- and post-re-LTx
      were collected and analyzed. A total of 143 patients underwent re-LTx for CLAD
      resulting in 94 BOS (66%) and 49 rCLAD (34%) patients. Unadjusted and adjusted
      survival after re-LTx for rCLAD was worse compared to BOS (HR = 2.60, 1.59-4.24;
      p < 0.0001 and HR = 2.61, 1.51-4.51; p = 0.0006, respectively). Patients waiting
      at home prior to re-LTx experienced better survival compared to hospitalized
      patients (HR 0.40; 0.23-0.72; p = 0.0022). Patients with rCLAD redeveloped CLAD
      earlier and were more likely to redevelop rCLAD. Survival after re-LTx for rCLAD
      is worse compared to BOS. Consequently, re-LTx for rCLAD should be critically
      discussed, particularly when additional peri-operative risk factors are present. 

PMID- 25940520
TI  - Stent Thrombosis and Dual Antiplatelet Therapy Interruption With Everolimus
      Eluting Stents: Insights From the Xience V Coronary Stent System Trials.
AB  - BACKGROUND: Whether premature dual antiplatelet therapy (DAPT) interruption is
      safe in patients receiving cobalt chromium everolimus-eluting stents remains
      controversial. We sought to examine the relationship between DAPT discontinuation
      and stent thrombosis (ST) after cobalt chromium everolimus-eluting stents.
      METHODS AND RESULTS: Outcomes from 11,219 patients were pooled from 3 randomized
      trials and 4 registries with 2-year follow-up period after cobalt chromium
      everolimus-eluting stent implantation. Rates of definite/probable ST were
      analyzed according to DAPT discontinuation in the following time intervals: 0 to
      30, 30 to 90, 90 to 180, 180 to 365, and 365 to 730 days. Eighty-five cases of ST
      (0.75%) occurred in 83 patients during 2 years, with 41 (48.2%) events occurring
      within 30 days. The 2-year ST rate in patients interrupting DAPT at any time was
      similar to that in patients never interrupting DAPT through 2 years (25/4067
      [0.63%] versus 58/7152 [0.83%] respectively; P=0.27]. By propensity and DAPT
      usage-adjusted multivariable analysis, permanent DAPT discontinuation before 30
      days was independently associated with the occurrence of ST (hazard ratio [95%
      confidence interval], 26.8 [8.4-85.4]; P<0.0001), whereas permanent DAPT
      discontinuation in any interval after 90 days was not associated with ST. Only 2
      ST events occurred after DAPT discontinuation between 30 and 90 days (both
      between 30 and 60 days), and the association between permanent DAPT
      discontinuation and ST during this period is unclear (hazard ratio [95%
      confidence interval], 8.7 [2.0-37.3]; P=0.004 for adjusted analysis and 3.4 [0.8
      13.8]; P=0.07 for the unadjusted analysis). CONCLUSIONS: In this large pooled
      experience, permanent DAPT discontinuation before 30 days after cobalt chromium
      everolimus-eluting stent implantation was strongly associated with ST, whereas
      DAPT discontinuation beyond 90 days appeared safe. CLINICAL TRIAL REGISTRATION:
      URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180310, NCT00180479,
      NCT00307047, NCT00402272, NCT00496938, NCT00676520, and NCT00631228.

PMID- 25940522
TI  - Pharmacokinetics of sirolimus-eluting stents implanted in the neonatal arterial
      duct.
AB  - BACKGROUND: Sirolimus-eluting stents may have clinical advantages over bare-metal
      stents in the extremely proliferative environment of the neonatal arterial duct.
      However, sirolimus has immunosuppressive actions and little is known regarding
      sirolimus pharmacokinetics in the newborn. METHODS AND RESULTS: This is a
      retrospective review of sirolimus pharmacokinetics in neonates who underwent
      sirolimus-eluting stent implantation in the arterial duct for pulmonary blood
      flow augmentation. Pharmacokinetic parameters were obtained by noncompartmental
      analysis and by a Bayesian one-compartment nonlinear mixed model. Nine neonates
      received a single sirolimus-eluting stent with a total sirolimus dose of 245 MUg
      (n = 1), 194 MUg (n = 5), or 143 MUg (n = 3). Peak sirolimus concentrations were
      13.6 +/- 4.5 MUg/L (24.8 MUg/L highest) and clearance was 0.042 +/- 0.03 L/hour
      (noncompartmental analysis) and 0.051 L/hour (95% credible intervals 0.037-0.069,
      nonlinear mixed model). Sirolimus remained > 5 MUg/L, the trough level used in
      oral immunosuppressive therapy, for (95% credible interval) 15.9 (11.4, 22.8),
      12.9 (7.6, 19.0), and 8.4 (2.3, 14.5) days for the 245, 194, and 143 MUg
      sirolimus dose stents, respectively. Estimates of the duration of systemic
      immunosuppression are provided for combinations of 2 stents. CONCLUSIONS: In
      neonates after sirolimus-eluting stent implantation, peak sirolimus levels were
      20 * higher and clearance 30 * lower than previously reported in older children
      and adults. Sirolimus levels were within the immunosuppressive range for a
      prolonged period, but with no observable clinically significant adverse outcomes.

PMID- 25940521
TI  - Incremental Value of Platelet Reactivity Over a Risk Score of Clinical and
      Procedural Variables in Predicting Bleeding After Percutaneous Coronary
      Intervention via the Femoral Approach: Development and Validation of a New
      Bleeding Risk Score.
AB  - BACKGROUND: Growing evidence suggests that platelet reactivity (PR) may predict
      bleeding. We investigate the incremental value of PR in predicting bleeding after
      percutaneous coronary intervention (PCI) via the femoral approach over a
      validated bleeding risk score (BRS) of clinical and procedural variables. METHODS
      AND RESULTS: A total of 800 patients undergoing elective PCI via the femoral
      approach were included. PR was measured before PCI with the VerifyNow P2Y12 assay
      and low PR was defined as a P2Y12 reaction unit value <= 178. Calculation of the
      BRS included the following: age, sex, intra-aortic balloon pump, glycoprotein
      IIb/IIIa inhibitors, chronic kidney disease, anemia, and low-molecular-weight
      heparin within 48-hour pre-PCI. A new risk score including low PR (BRS-PR) was
      developed and validated in an independent cohort of patients (n = 310). Bleeding
      events at 30 days after PCI were defined according to the thrombolysis in
      myocardial infarction, Randomized Evaluation in PCI Linking Angiomax to Reduced
      Clinical Events (REPLACE)-2, and Bleeding Academic Research Consortium criteria.
      Both BRS and PR showed high discriminatory power for bleeding (area under the
      curve [AUC] > 0.7 for all definitions). Discriminatory power of BRS-PR (AUC =
      0.809 for thrombolysis in myocardial infarction bleeding; AUC = 0.814 for
      Bleeding Academic Research Consortium class >= 2 bleeding; AUC = 0.708 for
      Bleeding Academic Research Consortium class >= 3 bleeding; and AUC = 0.813 for
      REPLACE-2 bleeding) was significantly higher than that of BRS alone (P < 0.001
      for all bleeding definitions). In the validation set, BRS-PR showed higher
      discriminatory power for thrombolysis in myocardial infarction bleeding than BRS
      alone (AUC = 0.788 versus 0.709; P = 0.036). CONCLUSIONS: PR has incremental
      predictive value on bleeding events after elective PCI via the femoral approach
      over a validated risk score of clinical and procedural variables. A risk score
      including PR yields significantly better prognostic performance compared with the
      original BRS.

PMID- 25940523
TI  - Neuromatous regeneration as a nerve response after catheter-based renal
      denervation therapy in a large animal model: immunohistochemical study.
AB  - BACKGROUND: Renal denervation (RDN) emerged as a therapeutic option for resistant
      hypertension. Nerve regrowth after RDN has been questioned. We aimed to
      characterize the nerve response after RDN. METHODS AND RESULTS: Swine underwent
      bilateral RDN and were followed up for 7, 30, and 90 days and evaluated with S100
      (Schwann cell), tyrosine hydroxylase (TH; efferent nerves), and growth-associated
      protein 43 (neurite regeneration) markers. At 7 days, nerve changes consisted of
      necrosis associated with perineurial fibrosis and distal atrophy with
      inflammation. At 30 days changes were substituted by healing changes (ie,
      fibrosis). This response progressed through 90 days resulting in prominent
      neuroma formation. Immunohistochemistry at 7 days: TH staining was strongly
      decreased in treated nerves. Early regenerative attempts were observed with
      strongly TH and growth-associated protein 43 positive and weak S100 disorganized
      nerve sprouts within the thickened perineurium. Distal atrophic nerves show weak
      staining for all 3 markers. At 30 days, affected nerves show a weak TH and S100
      staining. Evident growth-associated protein 43+ disorganized neuromatous tangles
      in the thickened perineurium of severed nerves were observed. At 90 days, some TH
      expression was observed together with prominent S100+ and growth-associated
      protein 43+ neuromatous tangles with disorganized architecture. The potential for
      regenerative activity is unlikely based on the disrupted architecture of these
      neuromatous tangles at the radiofrequency lesion sites. CONCLUSIONS: This study
      is the first documentation that a progressive regenerative response occurs as
      early as 7 days after RDN, resulting in a poorly organized neuromatous
      regeneration. This finding is of paramount importance to further establish the
      potential functional significance of a regeneration after RDN.

PMID- 25940524
TI  - Study on interaction between curcumin and pepsin by spectroscopic and docking
      methods.
AB  - The interaction between curcumin and pepsin was investigated by fluorescence,
      synchronous fluorescence, UV-vis absorption, circular dichroism (CD), and
      molecular docking. Under physiological pH value in stomach, the fluorescence of
      pepsin can be quenched effectively by curcumin via a combined quenching process.
      Binding constant (Ka) and binding site number (n) of curcumin to pepsin were
      obtained. According to the theory of Forster's non-radiation energy transfer, the
      distance r between pepsin and curcumin was found to be 2.45 nm within the
      curcumin-pepsin complex, which implies that the energy transfer occurs between
      curcumin and pepsin, leading to the quenching of pepsin fluorescence.
      Fluorescence experiments also suggest that curcumin is located more closely to
      tryptophan residues than tyrosine residues. CD spectra together with UV-vis
      absorbance studies show that binding of curcumin to pepsin results in the
      extension of peptide strands of pepsin with loss of some beta-sheet structures.
      Thermodynamic parameters calculated from the binding constants at different
      temperatures reveal that hydrophobic force plays a major role in stabilizing the
      curcumin-pepsin complex. In addition, docking results support the above
      experimental findings and suggest the possible hydrogen bonds of curcumin with
      Thr-77, Thr-218, and Glu-287 of pepsin, which help further stabilize the curcumin
      pepsin complex.

PMID- 25940519
TI  - Plasma glucose and hemoglobin A1c for the detection of diabetes in Chinese
      adults.
AB  - BACKGROUND: The aim of the present study was to evaluate the performance of
      plasma glucose (PG) and HbA1c for the detection of diabetes in the general
      population in China. METHODS: A cross-sectional analysis was conducted in a
      nationally representative sample of 98,658 Chinese adults aged >=18 years.
      Fasting plasma glucose and HbA1c levels were measured in all participants after
      at least a 10-h overnight fast. An oral glucose tolerance test (OGTT) was
      conducted among participants without a self-reported history of diagnosed
      diabetes. RESULTS: An HbA1c >=6.5% could identify 4.57% of Chinese adults as
      having newly detected diabetes, followed by fasting PG (FPG) and 2-h PG at 4.52%
      and 3.50%, respectively. Approximately 1.95% of the total population was detected
      by HbA1c but not by FPG or 2-h PG. However, FPG plus HbA1c could identify most
      (85.2%) diabetic individuals identified by any of the three tests (i.e., FPG, 2-h
      PG, and HbA1c). Levels of most cardiovascular risk factors, such as body mass
      index, waist circumference, and cholesterol, were higher in diabetes detected by
      HbA1c alone than in diabetes identified by the OGTT. CONCLUSIONS: Although HbA1c
      >=6.5% has been recommended by the American Diabetes Association as one of the
      diagnostic tests for diabetes, caution should be used to avoid potential
      overdiagnosis when interpreting diabetes identified by elevated HbA1c alone.

PMID- 25940525
TI  - Design of cissus-alginate microbeads revealing mucoprotection properties in anti
      inflammatory therapy.
AB  - Cissus gum has been employed as polymer with sodium alginate in the formulation
      of diclofenac microbeads and the in vivo mucoprotective properties of the polymer
      in anti-inflammatory therapy assessed in rats with carrageenan-induced paw edema
      in comparison to diclofenac powder and commercial diclofenac tablet. A full 2(3)
      factorial experimental design has been used to investigate the influence of
      concentration of cissus gum (X1); concentration of calcium acetate (X2) and
      stirring speed (X3) on properties of the microbeads. Optimized small discrete
      microbeads with size of 1.22+/-0.10 mm, entrapment efficiency of 84.6% and t80 of
      15.2+/-3.5 h were obtained at ratio of cissus gum:alginate (1:1), low
      concentration of calcium acetate (5% w/v) and high stirring speed (400 rpm). In
      vivo studies showed that the ranking of percent inhibition of inflammation after
      3h was diclofenac powder>commercial tablet=cissus>alginate. Histological damage
      score and parietal cell density were lower while crypt depth and mucosal width
      were significantly higher (p<0.05) in the groups administered with the diclofenac
      microbeads than those administered with diclofenac powder and commercial tablet,
      suggesting the mucoprotective property of the gum. Thus, cissus gum could be
      suitable as polymer in the formulation of non-steroidal anti-inflammatory drugs
      ensuring sustained release while reducing gastric side effects.

PMID- 25940526
TI  - Minocycline-loaded cellulose nano whiskers/poly(sodium acrylate) composite
      hydrogel films as wound dressing.
AB  - In this work, antibiotic drug Minocycline (Mic) loaded cellulose nano-whiskers
      (CNWs)/poly(sodium acrylate) hydrogel films were prepared and investigated for
      their drug releasing capacity in physiological buffer solution (PBS) at 37 
      degrees C. The (CNWs)/poly(sodium acrylate) film, containing 9.7% (w/w) of CNWs,
      demonstrated Mic release of 2500 MUg/g while the plain poly(acrylate) film showed
      3100 MUg/g of drug release. In addition, with the increase in the concentration
      of cross-linker N,N'-methylene bisacrylamide (MB) from to, the drug release from
      the resulting films decreased from 507 to 191 MUg/g. The release exponent 'n' for
      films with different compositions was found in the range of 0.45 to 0.89, thus
      indicating non-Fickian release mechanism. The Schott model was employed to
      interpret the kinetic drug release data successfully. The film samples poly(SA)
      and CNWs/poly(SA) (both not containing drug) showed thrombus formation of 0.010+/
      0.001 g and 0.007+/-0.001 g, respectively, thus showing the non-thrombogenic
      behavior. In percent Hemolysis, both of the film samples of 1.136+/-0.012 and
      0.5+/-0.020, respectively, thus indicating non-hemolytic behavior. In addition,
      both of the film samples demonstrated protein adsorption of 49.02+/-0.59MU g/MUL
      and 51.20+/-0.51 MUg/MUL per cm(2), thus revealing a fair degree of protein
      adsorption. Finally, the Mic-loaded films showed fair anti-fungal and
      antibacterial properties.

PMID- 25940527
TI  - Effects of the I682F mutation on JAK2's activity, structure and stability.
AB  - Janus kinase 2 (JAK2) plays important roles in the regulation of varieties
      cellular processes including cell migration, proliferation and apoptosis. JAK2
      I682F genetic mutation existed in the 4-8% of B-cell acute lymphoblastic leukemia
      (B-ALL). However, roles of this mutation in the development of B-ALL are still
      unknown. In order to investigation the mechanism of the JAK2 I682F mutation led
      to B-ALL, series of mutations were constructed. Mutations I682F, I682G, I682D and
      I682S significantly increased JAK2's activity and decreased its structural
      stability, while the I682L mutation almost had no effect on JAK2's activity and
      structural stability. Furthermore, the spectroscopic experiments implied that
      mutations I682F, I682G, I682D and I682S impaired the structure of JAK2 JH2
      domain, and led JAK2 to the partially unfolded state. It may be this partially
      unfolded state that caused JAK2 I682F constitutive activation. This study
      provides clues in understanding the mechanism of the JAK2 I682F mutation caused B
      ALL. 

PMID- 25940528
TI  - The effect of hyaluronan on the motility of skin dermal fibroblasts in
      nanofibrous scaffolds.
AB  - Nanofibrous scaffolds that use the native extracellular matrix are promising
      developments in skin tissue regeneration because they provide the proper
      environment for the adhesion, migration and growth of skin dermal fibroblasts,
      important during wound healing. In this study, we focus on hyaluronan as a native
      ECM that regulates cellular motility in nanofibrous scaffolds. PCL/HA nanofibrous
      scaffolds were generated by electrospinning and assessed for various
      physicochemical properties. HA-based scaffolds significantly enhanced cell
      infiltration in vitro and in vivo. The observation of movements in living cells
      revealed that HA-based scaffolds regulated cell migration speed and direction.
      This phenomenon may influences by the variation in cell adhesion receptors
      integrin beta1, and vinculin formation and distribution. Furthermore, we
      confirmed that HA/CD44 interactions can activate the TGF-beta/MMP-2 signaling
      pathway that promotes cell motility. These findings suggest HA functions in the
      cell motility of nanofibrous scaffolds and have potential implications for the
      use of HA-based scaffolds in skin tissue regeneration applications. 

PMID- 25940529
TI  - Insight into the adsorption mechanisms of vanadium(V) on a high-efficiency
      biosorbent (Ti-doped chitosan bead).
AB  - In this present study, a new chitosan bead modified with titanium ions (TiCB) was
      prepared and employed for the adsorption of vanadium ions from aqueous solutions.
      Batch adsorption experiments were performed to research the effect of various
      factors, including pH, temperature, contact time and initial concentration of
      vanadium(V) ions. The adsorption of vanadium was followed by the pseudo second
      order kinetic and the Langmuir isotherm model, with a remarkable maximum
      adsorption capacity of 210 mg/g. The analysis of thermodynamic parameters (DeltaG
      degrees , DeltaH degrees  and DeltaS degrees ) revealed that the nature of
      adsorption was feasible, spontaneous (DeltaG degrees <0) and endothermic (DeltaH
      degrees >0) process. FTIR, EDS, EMI and XPS studies suggested that the mechanisms
      of adsorption were possibly attributed to electrostatic attraction, ligand
      exchange and redox reaction between TiCB and vanadium ions.

PMID- 25940530
TI  - Dacarbazine as a minor groove binder of DNA: Spectroscopic, biophysical and
      molecular docking studies.
AB  - A detailed investigation on the mode of action and binding mechanism of a potent
      anticancer drug, 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DCR) with
      calf thymus DNA (ctDNA) was carried out. UV-vis and fluorescence
      spectrophotometry suggested the formation of complex between DCR and ctDNA. The
      binding constant (Kb) determined by ITC was 7.89*10(4) M(-1). Thermodynamic
      parameters obtained by isothermal calorimetry suggested the spontaneous free
      energy (DeltaG<0) and large favorable enthalpy driven (DeltaH<0) reaction,
      indicating the key role of hydrogen bonding and van der Waals forces in groove
      binding process. Moreover, DNA-melting and circular dichroism as well as
      competitive displacement studies with ethidium bromide, Hoechst 33258 and
      potassium iodide, clearly established the formation of a groove binding system
      between the DCR and ctDNA. Molecular docking analysis further confirmed DCR to be
      a minor groove binder involving hydrogen bonding mediated 'A-T'-rich region of 'B
      DNA'.

PMID- 25940531
TI  - First chitin extraction from Plumatella repens (Bryozoa) with comparison to
      chitins of insect and fungal origin.
AB  - Chitin immediately suggests the representatives of the kingdom Fungi, as well as
      such phyla as Annelida, Mollusca, Porifera, Cnidaria and, mostly, Arthropoda.
      Although Bryozoa also represents a chitin-containing phylum, no study has been
      developed yet on the isolation or characterization of the chitin from it. In this
      study, physiochemical properties of the chitin isolated from Plumatella repens
      belonging to the phylum Bryozoa was determined for the first time. The chitin
      structure was also studied comparatively by isolating chitin from an insect
      species (Palomena prasina) of the phylum Arthropoda, and Fomes fomentarius
      belonging to the kingdom Fungi. It was observed that the bryozoan chitin was in
      the alpha form, as in the arthropod and fungal chitins. The chitin contents in
      the dry weight of the bryozoan, fungal and insect species were observed to be
      13.3%, 2.4%, and 10.8%, respectively. The insect chitin exhibited the highest
      thermal stability followed by that of the bryozoan and then the fungal chitins.
      Surface morphologies reveal that the insect and bryozoan chitins were composed of
      nano fibre and pore structures, whereas the fungal chitin had no pores or fibres.
      The crystallinity of the insect chitin (CrI=84.9%) was higher than the bryozoan
      (CrI=60.1%) and fungal chitins (CrI=58.5%). 

PMID- 25940533
TI  - Lysosomal dysfunction and impaired autophagy underlie the pathogenesis of
      amyloidogenic light chain-mediated cardiotoxicity.

PMID- 25940532
TI  - Neural underpinnings of the 'agent brain': new evidence from transcranial direct
      current stimulation.
AB  - Intentional binding (IB) refers to the temporal compression between a voluntary
      action and its sensory effect, and it is considered an implicit measure of sense
      of agency (SoA), that is, the capacity to control one's own actions. IB has been
      thoroughly studied from a behavioural point of view but only few studies have
      investigated its neural underpinnings, always using the same two paradigms.
      Although providing evidence that the supplementary motor complex is involved,
      findings are still too scarce to draw definitive conclusions. The aim of the
      present study was to establish a causal relationship between the pre
      supplementary motor area (pre-SMA), known for its key role in action planning and
      initiation, and IB by means of transcranial direct current stimulation (tDCS).
      Participants underwent anodal, cathodal and sham control stimulations during
      three separate sessions (Experiment I). Subsequently, they underwent the same
      stimulation protocol (Experiment II) using as control a region potentially
      involved in the processing of the sensory effects of voluntary action (i.e., the
      right primary auditory cortex for the auditory effects of action). A significant
      reduction in IB was found only after stimulation of the pre-SMA, which supports
      the causal contribution of this prefrontal area in the perceived linkage between
      action and its effects. As SoA could be disrupted in many psychiatric and
      neurological diseases, these results have direct clinical relevance as tDCS could
      be successfully used in this domain in virtue of the promising advantages it
      offers for rehabilitation. 

PMID- 25940534
TI  - High-concentration boron doping of graphene nanoplatelets by simple thermal
      annealing and their supercapacitive properties.
AB  - For the utilization of graphene in various energy storage and conversion
      applications, it must be synthesized in bulk with reliable and controllable
      electrical properties. Although nitrogen-doped graphene shows a high doping
      efficiency, its electrical properties can be easily affected by oxygen and water
      impurities from the environment. We here report that boron-doped graphene
      nanoplatelets with desirable electrical properties can be prepared by the
      simultaneous reduction and boron-doping of graphene oxide (GO) at a high
      annealing temperature. B-doped graphene nanoplatelets prepared at 1000  degrees C
      show a maximum boron concentration of 6.04 +/- 1.44 at %, which is the highest
      value among B-doped graphenes prepared using various methods. With well-mixed GO
      and g-B2O3 as the dopant, highly uniform doping is achieved for potentially gram
      scale production. In addition, as a proof-of-concept, highly B-doped graphene
      nanoplatelets were used as an electrode of an electrochemical double-layer
      capacitor (EDLC) and showed an excellent specific capacitance value of 448 F/g in
      an aqueous electrolyte without additional conductive additives. We believe that B
      doped graphene nanoplatelets can also be used in other applications such as
      electrocatalyst and nano-electronics because of their reliable and controllable
      electrical properties regardless of the outer environment. 

PMID- 25940535
TI  - Scaling up combined community-based HIV prevention interventions targeting truck
      drivers in Morocco: effectiveness on HIV testing and counseling.
AB  - BACKGROUND: Truck drivers constitute an important bridging group in the HIV
      epidemic in Morocco. This study examined the effect of a community-based
      educational intervention in Morocco on HIV testing and counseling, in
      representative samples of truck drivers before (2007) and after (2012) the
      intervention. METHODS: Face-to-face structured interviews, adapted from UNAIDS
      documents, collected data on socio-demographic characteristics, HIV testing and
      counseling, and HIV risk behaviors in both the 2007 and 2012 surveys. Information
      about exposure to the intervention was also collected in the latter. Individuals
      exposed to the intervention were compared with those unexposed (i.e. unexposed in
      2012, and all the 2007 pre-intervention sample). RESULTS: The 2012 group included
      459 men with a median [IQR] age of 38 [31-44] years, 53% of whom reported
      exposure to the educational intervention. The percentage of participants tested
      for HIV and receiving HIV counseling in the last 12 months, was significantly
      higher in the 2012 group (29.6% vs 4.3% in 2007). Data from the 2012 survey
      confirmed a significant positive trend between being HIV tested and receiving
      counseling and the number of times a participant was exposed to the intervention
      (once: (OR = 5.17(2.38-11.25)), twice or more (OR = 19.16(10.33 - 35.53)). These
      results were confirmed after adjustment for employment, knowledge that the HIV
      test results would remain confidential, inconsistent condom use with occasional
      partners or sex workers, and when including individuals from 2007 considered
      unexposed. CONCLUSIONS: Community-based educational interventions targeting truck
      drivers can be effective in increasing coverage of HIV testing and counseling,
      particularly if they are repeated and cover a considerable portion of this at
      risk population. These results are encouraging for other countries which urgently
      need to implement prevention interventions for most-at-risk populations.
      Furthermore, they clearly show the power of community-based organization
      interventions in settings where resources for HIV prevention remain limited.

PMID- 25940536
TI  - Predictors of long-term quality of life after pediatric epilepsy surgery.
AB  - OBJECTIVE: This study examined the influence of seizures, antiepileptic drugs
      (AEDs), intelligence quotient (IQ), and symptoms of depression and anxiety on
      health-related quality of life (HRQOL) 4-11 years after pediatric epilepsy
      surgery. METHODS: Participants were 109 patients with childhood-onset intractable
      epilepsy; 71 had undergone surgery on average 6.9 years before this study.
      Patients and their parents completed questionnaires assessing HRQOL and
      internalizing behavior, a measure of depression and anxiety symptoms. RESULTS:
      Similar rates of recent seizure freedom were found for surgical and nonsurgical
      patients, although surgical patients had achieved seizure freedom sooner and with
      fewer AEDs. Few differences were found between surgical and nonsurgical patients.
      Differences emerged when comparing patients with continued seizures and those who
      had been seizure-free in the 12 months preceding the study. Almost all HRQOL
      ratings were enhanced in seizure-free patients. Internalizing behavior
      (anxiety/depression) mediated the relationship between seizure freedom and better
      HRQOL, where seizure freedom led to better ratings of anxiety/depression, which
      in turn led to better ratings of HRQOL. AED use was found to be associated with
      social functioning, medication effects, and seizure worry. IQ and duration of
      follow-up were not found to independently influence HRQOL. SIGNIFICANCE: The
      findings highlight the integral role of depression and anxiety symptoms in
      determining HRQOL; seizure control seems to play a secondary role. This study
      expands this relationship to individuals who have a history of intractable
      childhood epilepsy. The findings highlight the importance of managing depression
      and anxiety in improving the HRQOL and reducing seizure burden on patients.

PMID- 25940538
TI  - Sleep variability and fatigue in adolescents: Associations with school-related
      features.
AB  - This study aims to evaluate the influences of sleep duration and sleep
      variability (SleepV), upon adolescents' school-related situations. The Health
      Behaviour in School-Aged Children (HBSC) survey is based on a self-completed
      questionnaire. The participants were 3164 pupils (53.7% girls), attending the 8th
      and 10th grades, 14.9 years old, and were inquired about subjective sleep
      duration during the week and weekends, SleepV, fatigue, difficulties in sleep
      initiation, school achievement, feelings towards schools, pressure with school
      work and skipping classes. Multiple regression models used, as dependent
      variables: (a) school achievement, (b) disliking school, (c) pressure with school
      work and (d) skipping classes, using as independent variables, each of the
      remaining school-related variables, fatigue, total sleep duration and
      difficulties in sleep initiation. The average sleep duration in the week and
      during weekdays was lower than recommended for these age groups, and almost half
      of students had high SleepV between weekdays and weekends. A logistic model
      revealed that the absence of SleepV was associated with lower perception of
      school work pressure, less frequent skipping classes, more infrequent fatigue and
      more infrequent difficulties in sleep initiation. Poor sleep quality, SleepV and
      insufficient sleep duration affected negatively school-related variables. 

PMID- 25940537
TI  - Rivaroxaban in antiphospholipid syndrome (RAPS) protocol: a prospective,
      randomized controlled phase II/III clinical trial of rivaroxaban versus warfarin
      in patients with thrombotic antiphospholipid syndrome, with or without SLE.
AB  - INTRODUCTION: The current mainstay of the treatment of thrombotic
      antiphospholipid syndrome (APS) is long-term anticoagulation with vitamin K
      antagonists (VKAs) such as warfarin. Non-VKA oral anticoagulants (NOACs), which
      include rivaroxaban, have been shown to be effective and safe compared with
      warfarin for the treatment of venous thromboembolism (VTE) in major phase III
      prospective, randomized controlled trials (RCTs), but the results may not be
      directly generalizable to patients with APS. AIMS: The primary aim is to
      demonstrate, in patients with APS and previous VTE, with or without systemic
      lupus erythematosus (SLE), that the intensity of anticoagulation achieved with
      rivaroxaban is not inferior to that of warfarin. Secondary aims are to compare
      rates of recurrent thrombosis, bleeding and the quality of life in patients on
      rivaroxaban with those on warfarin. METHODS: Rivaroxaban in antiphospholipid
      syndrome (RAPS) is a phase II/III prospective non-inferiority RCT in which
      eligible patients with APS, with or without SLE, who are on warfarin, target
      international normalized ratio (INR) 2.5 for previous VTE, will be randomized
      either to continue warfarin (standard of care) or to switch to rivaroxaban.
      Intensity of anticoagulation will be assessed using thrombin generation (TG)
      testing, with the primary outcome the percentage change in endogenous thrombin
      potential (ETP) from randomization to day 42. Other TG parameters, markers of in
      vivo coagulation activation, prothrombin fragment 1.2, thrombin antithrombin
      complex and D-dimer, will also be assessed. DISCUSSION: If RAPS demonstrates i)
      that the anticoagulant effect of rivaroxaban is not inferior to that of warfarin
      and ii) the absence of any adverse effects that cause concern with regard to the
      use of rivaroxaban, this would provide sufficient supporting evidence to make
      rivaroxaban a standard of care for the treatment of APS patients with previous
      VTE, requiring a target INR of 2.5.

PMID- 25940540
TI  - First principles prediction of interfacial magnetoelectric coupling in tetragonal
      La2/3Sr1/3MnO3/BiFeO3 multiferroic superlattices.
AB  - The electronic structure and magnetic properties of the tetragonal
      La2/3Sr1/3MnO3/BiFeO3 multiferroic superlattices with different interfacial
      terminations have been studied by first-principles calculations. Our results for
      all the models of the tetragonal La2/3Sr1/3MnO3/BiFeO3 superlattices exhibit a
      metallic electronic structure. More importantly, we find that the magnetoelectric
      coupling can be realized in the tetragonal La2/3Sr1/3MnO3/BiFeO3 heterostructures
      by means of exchange bias, which can be attributed to the interfacial exchange
      coupling. These findings are useful for magnetoelectrically controlled spintronic
      devices. 

PMID- 25940541
TI  - Examining experiences of transition, instability and coping for young offenders
      in the community: A qualitative analysis.
AB  - This article explores experiences of transition, instability and coping using a
      qualitative approach with young offenders within a specialist forensic child and
      adolescent mental health service (CAMHS). Participants were four young people
      (aged 14-17 years) on community orders under the supervision of local youth
      offending teams (YOTs). Semi-structured interviews were conducted and data
      analysed using an inductive thematic analysis approach. Three main themes were
      identified: (i) people and places; (ii) growth; and (iii) managing difficult
      experiences. Findings suggest that young offenders are exposed to a wide range of
      challenging contextual factors including unpredictable or inadequate home
      environments, numerous transitions (between family members/foster placements and
      schools), limited engagement with educational settings and a lack of social
      support, supporting the findings of Paton et al. Findings also portrayed a sense
      of participants' 'psychological growth' with development along a trajectory from
      a young child 'acting out' in response to the environments in which they were
      living; through a more reflective stage, in which they were able to begin to
      consider the situations they found themselves in; before reaching a position in
      which they were able to look beyond their day-to-day circumstances with some hope
      that their lives could be different in the future. Furthermore, accounts revealed
      that these young people had a limited range of functional coping strategies and
      had largely negative experiences of services. Clinical implications and the need
      for further research developing professionals' understanding of the influence of
      early experiences on young offenders' behaviour are discussed. 

PMID- 25940539
TI  - Dual inhibition of HDAC and EGFR signaling with CUDC-101 induces potent
      suppression of tumor growth and metastasis in anaplastic thyroid cancer.
AB  - Anaplastic thyroid cancer (ATC) is one of the most lethal human malignancies that
      currently has no effective therapy. We performed quantitative high-throughput
      screening (qHTS) in three ATC cell lines using 3,282 clinically approved drugs
      and drug candidates, and identified 100 active agents. Enrichment analysis of
      active compounds showed that inhibitors of EGFR and histone deacetylase (HDAC)
      were most active. Of these, the first-in-class dual inhibitor of EGFR, HER2 and
      HDACs, CUDC-101, had the highest efficacy and lower IC50 than established drugs.
      We validated that CUDC-101 inhibited cellular proliferation and resulted in cell
      death by inducing cell cycle arrest and caspase-dependent apoptosis. CUDC-101
      also inhibited cellular migration in vitro. Mechanistically, CUDC-101 inhibited
      MAPK signaling and histone deacetylation in ATC cell lines with multiple driver
      mutations present in human ATC. The anticancer effect of CUDC-101 was associated
      with increased expression of p21 and E-cadherin, and reduced expression of
      survivin, XIAP, beta-catenin, N-cadherin, and Vimentin. In an in vivo mouse model
      of metastatic ATC, CUDC-101 inhibited tumor growth and metastases, and
      significantly prolonged survival. Response to CUDC-101 treatment in vivo was
      associated with increased histone 3 acetylation and reduced survivin expression.
      Our findings provide a preclinical basis to evaluate CUDC-101 therapy in ATC. 

PMID- 25940542
TI  - X-ray photonic microsystems for the manipulation of synchrotron light.
AB  - Photonic microsystems played an essential role in the development of integrated
      photonic devices, thanks to their unique spatiotemporal control and spectral
      shaping capabilities. Similar capabilities to markedly control and manipulate X
      ray radiation are highly desirable but practically impossible due to the massive
      size of the silicon single-crystal optics currently used. Here we show that
      micromechanical systems can be used as X-ray optics to create and preserve the
      spatial, temporal and spectral correlation of the X-rays. We demonstrate that, as
      X-ray reflective optics they can maintain the wavefront properties with nearly
      100% reflectivity, and as a dynamic diffractive optics they can generate
      nanosecond time windows with over 100-kHz repetition rates. Since X-ray photonic
      microsystems can be easily incorporated into lab-based and next-generation
      synchrotron X-ray sources, they bring unprecedented design flexibility for future
      dynamic and miniature X-ray optics for focusing, wavefront manipulation,
      multicolour dispersion, and pulse slicing. 

PMID- 25940543
TI  - Tyrosine hydroxylase positive perisomatic rings are formed around various
      amacrine cell types in the mammalian retina.
AB  - Dopaminergic neurons of the central nervous system are mainly found in nuclei of
      the midbrain and the hypothalamus that provide subcortical and cortical targets
      with a rich and divergent innervation. Disturbance of signaling through this
      system underlies a variety of deteriorating conditions such as Parkinson's
      disease and schizophrenia. Although retinal dopaminergic signaling is largely
      independent of the above circuitry, malfunction of the retinal dopaminergic
      system has been associated with anomalies in visual adaptation and a number of
      retinal disorders. Dopamine (DA) is released mainly in a paracrine manner by a
      population of tyrosine hydroxylase expressing (TH(+) ) amacrine cells (AC) of the
      mammalian retina; thus DA reaches virtually all retinal cell types by diffusion.
      Despite this paracrine release, however, the so called AII ACs have been
      considered as the main targets of DA signaling owing to a characteristic and
      robust ring-like TH(+) innervation to the soma/dendritic-stalk area of AII cells.
      This apparent selectivity of TH(+) innervation seems to contradict the divergent
      DAergic signaling scheme of other brain loci. In this study, however, we show
      evidence for intimate proximity between TH(+) rings and somata of neurochemically
      identified non-AII cells. We also show that this phenomenon is not species
      specific, as we observe it in popular mammalian animal models including the
      rabbit, the rat, and the mouse. Finally, our dataset suggests the existence of
      further, yet unidentified post-synaptic targets of TH(+) dendritic rings.
      Therefore, we hypothesize that TH(+) ring-like structures target the majority of
      ACs non-selectively and that such contacts are wide-spread among mammals.
      Therefore, this new view of inner retinal TH(+) innervation resembles the
      divergent DAergic innervation of other brain areas through the mesolimbic,
      mesocortical, and mesostriatal signaling streams. AII amacrine cells have been
      considered as the main targets of dopamine signaling in the mammalian retina
      owing to a characteristic ring-like innervation from dopaminergic (TH(+) )
      amacrine cells (green) to somata of AII cells (red). In this study, we show the
      intimate proximity of TH(+) rings and somata of non-AII cells, including
      starburst-a amacrine cells (blue) and other unidentified amacrine cells
      (magenta). We find that this phenomenon is not species specific and it occurs in
      a number of popular mammalian animal models. We hypothesize that TH(+) ring
      inputs target most amacrine cells non-selectively and thus it resembles the
      divergent dopaminergic innervation of other brain areas. 

PMID- 25940544
TI  - Anomalous Left Main Coronary Artery: Not Always a Simple Surgical Reimplantation.
AB  - We present the case of 56-year-old woman who required complex coronary artery
      bypass grafting for high-risk anomalous left main coronary artery (LMCA)
      originating from right coronary cusp including conventional reimplantation of the
      LMCA plus left internal mammary artery (LIMA) graft to the left anterior
      descending (LAD) and saphenous vein graft (SVG) to the left circumflex (LCx). On
      subsequent cardiac computed tomography screening and cardiac catheterization, the
      LIMA graft was occluded after just a few centimeters, but the SVG graft was
      patent with good run-off into the native LCx and also filled the LAD
      retrogradely. The reimplanted left main stem demonstrated at least moderate
      ostial stenosis although pressure wire assessment of this was not significant
      (fractional flow reserve 0.89), probably due to good retrograde filling of the
      LAD from the SVG to LCx, therefore, we did not proceed with ostial LMCA stenting.
      She remains on yearly review with a low threshold for further revascularization
      should the SVG to LCx develop progressive stenosis. This case illustrates how
      patients with anomalous LMCA may sometimes benefit from grafting in addition to
      conventional reimplantation. 

PMID- 25940545
TI  - The Contribution of the Cerebellum in the Hierarchial Development of the Self.
AB  - What distinguishes human beings from other living organisms is that a human
      perceives himself as a "self". The self is developed hierarchially in a multi
      layered process, which is based on the evolutionary maturation of the nervous
      system and patterns according to the rules and demands of the external world.
      Many researchers have attempted to explain the different aspects of the self, as
      well as the related neural substrates. In this paper, we first review the
      previously proposed ideas regarding the neurobiology of the self. We then suggest
      a new hypothesis regarding the hierarchial self, which proposes that the self is
      developed at three stages: subjective, objective, and reflective selves. In the
      second part, we attempt to answer the question "Why do we need a self?" We
      therefore explain that different parts of the self developed in an effort to
      identify stability in space, stability against constantly changing objects, and
      stability against changing cognitions. Finally, we discuss the role of the
      cerebellum as the neural substrate for the self. 

PMID- 25940546
TI  - Applications of protein engineering to members of the old yellow enzyme family.
AB  - In the 20 years since Massey's initial report in 1995, interest in using alkene
      reductases to prepare chiral intermediates for synthesis has grown rapidly. While
      native alkene reductases often show very high stereoselectivities toward
      favorable substrates, these enzymes have somewhat size-restricted active sites
      that limit their substrate ranges to small alkenes. In addition, most alkene
      reductases have the same stereoselectivities, which makes it difficult to access
      the "other" product enantiomers. Protein engineering strategies have been used to
      address both of these issues and good progress has been made in several cases.
      This review summarizes published examples through late 2014 and focuses on
      studies of six enzymes: Saccharomyces pastorianus OYE 1, tomato OPR1, Zymomonas
      mobilis NCR, Enterobacter cloacae PB2 PETN reductase, Bacillus subtilis YqjM and
      Pichia stipitis OYE 2.6.

PMID- 25940547
TI  - Overexpression of two alpha-esterase genes mediates metabolic resistance to
      malathion in the oriental fruit fly, Bactrocera dorsalis (Hendel).
AB  - Esterase has been reported to be involved in malathion resistance in the oriental
      fruit fly, Bactrocera dorsalis (Hendel). However, the underlying molecular
      mechanism of the esterase-mediated resistance remains largely unknown in this
      species. Here, with the use of a strain selected for malathion resistance in the
      laboratory (MR), we found that two overexpressed alpha-esterase genes, namely
      BdCarE4 and BdCarE6, predominant in the adult midgut and fat body, function in
      conferring malathion resistance in B. dorsalis. Notably, these two genes were
      found to be mostly close to the esterase E3, which are usually implicated in
      detoxifying organophosphate insecticides. The transcript levels of BdCarE4 and
      BdCarE6 were investigated and compared between the MR and a susceptible (MS)
      strain of B. dorsalis. Both genes were significantly up-regulated in the MR
      strain, which was consistent with the enhanced esterase activity in the MR
      strain. However, no changes in either the coding sequence or gene copy number
      were observed between the two strains. Subsequently, heterologous expression
      combined with cytotoxicity assay in Sf9 cells demonstrated that BdCarE4 and
      BdCarE6 can probably detoxify malathion. Furthermore, RNA interference-mediated
      knockdown of each of these two genes significantly increased malathion
      susceptibility in the MR strain adults. In conclusion, these results expand our
      molecular understanding of the important role of alpha-esterases during the
      development of resistance to organophosphorous insecticides in B. dorsalis. 

PMID- 25940548
TI  - Consistent differences in medical unit fall rates: implications for research and
      practice.
AB  - OBJECTIVES: To determine the proportion of variation in long-term fall rates
      attributable to variability between rather than within hospital units and to
      identify unit- and hospital-level characteristics associated with persistently
      low- and high-fall units. DESIGN: Retrospective study of administrative data on
      inpatient falls. Eighty low-fall and 74 high-fall units were identified based on
      monthly rankings of fall rates. Unit- and hospital-level characteristics of these
      units were compared. SETTING: U.S. general hospitals participating in the
      National Database of Nursing Quality Indicators. PARTICIPANTS: Nonsubspecialty
      medical units (n=800) with 24 consecutive months of falls data. MEASUREMENTS:
      Monthly self-reported unit fall rates (falls per 1,000 patient-days). RESULTS: An
      estimated 87% of variation in 24-month fall rates was due to between-unit
      differences. With the exception of patient-days, a proxy for unit bed size, low-
      and high-fall units did not differ on nurse staffing or any other unit or
      hospital characteristic variable. CONCLUSION: There are medical units with
      persistently low and persistently high fall rates. High-fall units had higher
      patient volume, suggesting patient turnover as a variable for further study.
      Understanding additional factors underlying variability in long-term fall rates
      could lead to sustainable interventions for reducing inpatient falls.

PMID- 25940549
TI  - Thrombospondin-1 (TSP1) contributes to the development of vascular inflammation
      by regulating monocytic cell motility in mouse models of abdominal aortic
      aneurysm.
AB  - RATIONALE: Histological examination of abdominal aortic aneurysm (AAA) tissues
      demonstrates extracellular matrix destruction and infiltration of inflammatory
      cells. Previous work with mouse models of AAA has shown that anti-inflammatory
      strategies can effectively attenuate aneurysm formation. Thrombospondin-1 is a
      matricellular protein involved in the maintenance of vascular structure and
      homeostasis through the regulation of biological functions, such as cell
      proliferation, apoptosis, and adhesion. Expression levels of thrombospondin-1
      correlate with vascular disease conditions. OBJECTIVE: To use thrombospondin-1
      deficient (Thbs1(-/-)) mice to test the hypothesis that thrombospondin-1
      contributes to pathogenesis of AAAs. METHODS AND RESULTS: Mouse experimental AAA
      was induced through perivascular treatment with calcium phosphate, intraluminal
      perfusion with porcine elastase, or systemic administration of angiotensin II.
      Induction of AAA increased thrombospondin-1 expression in aortas of C57BL/6 or
      apoE-/- mice. Compared with Thbs1(+/+) mice, Thbs1(-/-) mice developed
      significantly smaller aortic expansion when subjected to AAA inductions, which
      was associated with diminished infiltration of macrophages. Thbs1(-/-) monocytic
      cells had reduced adhesion and migratory capacity in vitro compared with wild
      type counterparts. Adoptive transfer of Thbs1(+/+) monocytic cells or bone marrow
      reconstitution rescued aneurysm development in Thbs1(-/-) mice. CONCLUSIONS:
      Thrombospondin-1 expression plays a significant role in regulation of migration
      and adhesion of mononuclear cells, contributing to vascular inflammation during
      AAA development.

PMID- 25940550
TI  - Efficient gene disruption in cultured primary human endothelial cells by
      CRISPR/Cas9.
AB  - RATIONALE: The participation of endothelial cells (EC) in many physiological and
      pathological processes is widely modeled using human EC cultures, but genetic
      manipulation of these untransformed cells has been technically challenging.
      Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR
      associated protein 9 nuclease (Cas9) technology offers a promising new approach.
      However, mutagenized cultured cells require cloning to yield homogeneous
      populations, and the limited replicative lifespan of well-differentiated human EC
      presents a barrier for doing so. OBJECTIVE: To create a simple but highly
      efficient method using CRISPR/Cas9 to generate biallelic gene disruption in
      untransformed human EC. METHODS AND RESULTS: To demonstrate proof-of-principle,
      we used CRISPR/Cas9 to disrupt the gene for the class II transactivator. We used
      endothelial colony forming cell-derived EC and lentiviral vectors to deliver
      CRISPR/Cas9 elements to ablate EC expression of class II major histocompatibility
      complex molecules and with it, the capacity to activate allogeneic CD4(+) T
      cells. We show the observed loss-of-function arises from biallelic gene
      disruption in class II transactivator that leaves other essential properties of
      the cells intact, including self-assembly into blood vessels in vivo, and that
      the altered phenotype can be rescued by reintroduction of class II transactivator
      expression. CONCLUSIONS: CRISPR/Cas9-modified human EC provides a powerful
      platform for vascular research and for regenerative medicine/tissue engineering.

PMID- 25940551
TI  - Interindividual epigenetic variation in ABCB1 promoter and its relationship with
      ABCB1 expression and function in healthy Chinese subjects.
AB  - AIM: Interindividual epigenetic variation is likely to be an important mechanism
      contributing to the interindividual variability in the expression and function of
      ATP-binding cassette, sub-family B, member 1 (ABCB1). The aim of the present
      study was to explore the effect of interindividual epigenetic variability in the
      ABCB1 promoter on ABCB1 expression and function in healthy Chinese subjects.
      METHODS: Using bisulfite sequencing polymerase chain reaction (PCR) and chromatin
      immunoprecipitation assays, the DNA methylation and histone acetylation status of
      the ABCB1 promoter in stool DNA and exfoliated colonic epithelial cells of 157
      healthy Chinese male volunteers was analysed. ABCB1 mRNA levels in colonic
      epithelial cells were detected by real-time PCR. The digoxin pharmacokinetics in
      subjects with different epigenetic profiles was investigated after a single oral
      administration of digoxin (0.5 mg). RESULTS: The methylation levels of ABCB1
      promoter in stool DNA showed a significant interindividual variation, from 0.84%
      to 18.05%. A high methylation level of the ABCB1 promoter was closely related to
      the low levels of acetylated histone H3 and ABCB1 mRNA expression. In the high
      methylation group, the area under the concentration-time curves (AUC(0-4 h) and
      AUC(0-10 h) ) of digoxin was increased by 19% [95% confidence interval (CI) 10%,
      31%; P = 0.024] and 13% (95% CI 8%, 26%; P = 0.026), respectively, and the peak
      concentration (Cmax ) of digoxin was increased by 30% (95% CI 12%, 41%; P =
      0.021) compared with the low methylation group. CONCLUSIONS: The epigenetic
      modifications of the ABCB1 promoter show high interindividual variability in
      healthy Chinese subjects, and are closely related to the interindividual
      variation in ABCB1 mRNA expression and digoxin 0-4 h plasma concentrations in
      vivo.

PMID- 25940552
TI  - The upregulation of zinc finger protein 670 and prostaglandin D2 synthase in
      proliferative vitreoretinopathy.
AB  - PURPOSE: Proteins in the vitreous play an important role on the induction of
      proliferative vitreoretinopathy (PVR) after retinal detachment. The aim of this
      study was to investigate the variation of protein patterns in the vitreous of PVR
      eyes and examine whether differentially expressed protein levels were expressed
      in experimental PVR retina. METHODS: Vitreous samples from PVR and macular hole
      patients were selected for proteomic analysis. The vitreous protein samples were
      separated by two-dimensional electrophoresis (2-DE). The differentially expressed
      protein spots in the two groups were excised and subjected to in-gel digestion
      and identification by electrospray ionization mass spectrometry (ESI-MS)
      analysis. Two differentially expressed proteins, zinc finger protein 670 (ZFP
      670) and prostaglandin D2 synthase (PGD2S), were further validated by
      immunohistochemical staining and western blotting analysis in the retina of the
      experimental rabbit PVR model. RESULTS: In proteome analysis of human vitreous
      samples, five proteins had increased expression in PVR, including zinc finger
      protein 670 (ZFP 670), prostaglandin D2 synthase (PGD2S), IgG (Immunoglobulin G)
      light chain, transthyretin precursor, and haptoglobin precursor. ZFP 670 and
      PGD2S levels were expressed significantly higher in the experimental PVR retinas
      than in the control group. CONCLUSIONS: Levels of ZFP 670 and PGD2S were elevated
      in the vitreous fluid of patients with PVR. In addition, there were higher
      expressions of ZFP 670 and PGD2S in the experimental PVR retina. This result will
      expand our knowledge of pathophysiologic characteristics of PVR, and might be
      helpful for further developing possible treatment on this disorder.

PMID- 25940553
TI  - Retinal structure in young patients aged 10 years or less with Best vitelliform
      macular dystrophy.
AB  - PURPOSE: Our aim was to analyze retinal structure in young patients with Best
      disease with reference to future gene therapy. METHODS: This was a retrospective
      observational spectral domain optical coherence tomography study of four patients
      aged 10 years or less with Best disease. RESULTS: Findings ranged from subtle
      thickening at the level of the retinal pigment epithelium-photoreceptor
      interdigitation line, to subretinal fluid and precipitate-like changes at the
      level of the photoreceptor outer segments, and further to choroidal
      neovascularization. The photoreceptor inner segment ellipsoid layer could be
      visualized seemingly undisturbed above the vitelliform lesions, except in the
      case of choroidal neovascularization. CONCLUSIONS: Clinical variability is
      evident even among young patients aged 10 years or less with Best disease. The
      earliest structural alterations seem to occur at the level of the retinal pigment
      epithelium-photoreceptor interdigitation line. The photoreceptor inner segment
      seems to be unaffected unless choroidal neovascularization develops, which seems
      promising regarding future gene therapy.

PMID- 25940554
TI  - Evaluating the long-term efficacy of short-duration 0.1 mg/ml and 0.2 mg/ml MMC
      in primary trabeculectomy for primary adult glaucoma.
AB  - OBJECTIVE: To evaluate safety and efficacy of 0.1 mg/ml versus 0.2 mg/ml
      mitomycin-C (MMC), applied for 1 min subconjunctivally, during trabeculectomy for
      primary adult glaucoma in previously un-operated eyes. MATERIALS AND METHODS:
      This is a randomised controlled, non-inferior, clinical trial consisting of 50
      consecutive POAG or CPACG patients uncontrolled on maximal hypotensive therapy,
      meeting all inclusion criteria. Patients were randomized into two groups and
      underwent a standard limbus-based trabeculectomy with MMC: Group I, 0.1 mg/ml and
      Group II, 0.2 mg/ml. The pre-operative and post-operative intraocular pressure
      (IOP), bleb morphology, and visual acuity were recorded every 6 months for 2
      years. Complete success (primary outcome) was defined as IOP <= 15 mmHg without
      any additional medications at the end of 2 years. RESULTS: The average age of
      patients was 62.6 +/- 9.8 years and 61.2 +/- 8.1 years in Group 1 and 2,
      respectively; p = 0.57. The mean preoperative IOP was 22.5 +/- 1.4 mmHg and 23.3
      +/- 1.8 mmHg; p = 0.10. The mean IOP at 2 years was 11.1 +/- 1.6 mmHg and 10.8 +/
      2.8 mmHg, a mean reduction in IOP of 50.6 +/- 1.23 %, and 53.7 +/- 2.25 % in
      Group I and II, respectively. The complete success was 92.0 % and 91.7 % in the
      two groups, respectively (p = 0.99), and there was one failure (Group II, post
      trauma). A wider bleb extent and larger areas of thin, transparent conjunctiva
      over the bleb were seen with the 0.2 mg/ml MMC group (p < 0.001) and in PACG
      eyes; p < 0.04. CONCLUSION: A 1-min subconjunctival application of low dose 0.1
      mg/ml MMC is non-inferior to 0.2 mg/ml and is probably a safer alternative, as
      thinning of the bleb is significantly less frequent in the long term.

PMID- 25940555
TI  - Real-life experience after intravitreal ocriplasmin for vitreomacular traction
      and macular hole: a spectral-domain optical coherence tomography prospective
      study.
AB  - PURPOSE: To evaluate prospectively the anatomical and functional results after
      ocriplasmin injection in patients with vitreomacular traction (VMT), or macular
      hole (MH) combined with VMT, providing the real-life experience of three centers,
      using spectral domain-optical coherence tomography (SD-OCT). METHODS: Twenty-four
      patients with VMT (17 with VMT alone and 7 with an MH combined with VMT) were
      treated with a single ocriplasmin injection and followed-up prospectively at
      baseline, day 1, 7, 28 and the last examination of the follow-up for each patient
      (range: 30-127 days). Best-corrected visual acuity (BCVA) and SD-OCT were
      performed for patient assessment, while various adverse events were recorded and
      analysed. At baseline, univariate analysis was also performed to examine the
      potential predictive factors for VMT release. RESULTS: 66.7 % of patients
      presented VMT release at the end of the follow-up, while 28.6 % exhibited MH
      closure. Baseline positive predictive factors for VMT release were young age,
      being female, phakic lens status, increased vitreofoveal angle, V-shaped and
      loose vitreomacular adhesion, small adhesion area, thin vitreous strands at the
      adhesion site and absence of an epiretinal membrane. Four new cases of ellipsoid
      line changes and subretinal fluid development became evident at day 7 compared to
      baseline. Lamellar macular hole (LMH) in four cases was first noticed at day 28
      post injection. Formation of cystoid macular edema (CME) was noticed in three new
      cases at day 28 compared to baseline. CONCLUSIONS: Our study demonstrated a VMT
      release rate of 66.7 %. Apart from the known baseline factors that influence VMT
      release after ocriplasmin injection, the size of the vitreofoveal angle, a V
      shaped and loose vitreomacular adhesion, a small adhesion area, and thin vitreous
      strands at the adhesion site, could additionally affect the outcome of VMT
      release. In addition, we studied when VMT release and concomitant events occur
      and for how long the induced complications lasted.

PMID- 25940557
TI  - Keeping enzymes kosher: Sacred and secular biotech production.

PMID- 25940558
TI  - Another face of RIPK1.
AB  - Receptor-interacting protein kinase-1 (RIPK1) sits at a signaling node
      controlling a number of functional pathways. These include both positive and
      negative control of apoptosis and necroptosis (a form of regulated necrosis). In
      this issue of EMBO Reports, Yonekawa and colleagues describe another function for
      RIPK1, the inhibition of autophagy via ERK-mediated phosphorylation of the
      transcription factor, TFEB [1]. Their findings are considered in the context of
      RIPK1 signaling, and how it is engaged.

PMID- 25940559
TI  - Mechanical circulatory support as a bridge to definitive surgical repair after
      post-myocardial infarct ventricular septal defect.
AB  - Ventricular septal defect (VSD) after myocardial infarction (MI) is an uncommon
      but serious complication. Patients refractory to attempts at medical
      stabilization and requiring emergency surgery have expected mortality rates
      greater than 50%. We present three cases of extracorporeal membrane oxygenation
      bridge to surgical repair in patients with multisystem organ failure who would
      otherwise require emergent cardiac surgery with associated risk and review the
      literature for mechanical circulatory support for patients with anterior and
      posterior post-MI VSD.

PMID- 25940556
TI  - The effect of prophylactic topical antibiotics on bacterial resistance patterns
      in endophthalmitis following intravitreal injection.
AB  - PURPOSE: The purpose of this study was to evaluate the effect of prophylactic
      topical antibiotics on bacterial resistance patterns in endophthalmitis following
      intravitreal injection of anti-vascular endothelial growth factor (VEGF)
      medications. METHODS: In this retrospective case-control study, billing records
      and an infection log were used to identify all cases of endophthalmitis following
      intravitreal injection of ranibizumab, bevacizumab, or aflibercept between
      January 1, 2009 and September 30, 2013 at a single retina practice. A 28-month
      period when topical antibiotic drops were prescribed for use four times a day for
      4 days following intravitreal injection was compared to a 21-month period when
      topical antibiotics were not prescribed. Patients treated during an 8-month
      transition period were excluded as prescription practices were changed. RESULTS:
      During the study period, a total of 172,096 anti-VEGF injections were performed.
      During the period when antibiotics were prescribed, 28 cases of suspected
      infectious endophthalmitis occurred from a total of 57,654 injections, ten of
      which were culture-positive. During the period when antibiotics were not used, 24
      cases of suspected endophthalmitis occurred from a total of 89,825 injections,
      six of which were culture-positive. During the antibiotic period, four of the ten
      (40 %) culture-positive cases grew bacteria resistant to the prescribed
      prophylactic antibiotics. In contrast, none of the six culture-positive cases
      grew bacteria resistant to those antibiotics during the period when antibiotics
      were not used (odds ratio = 9.0; 95 % confidence interval = 0.40-203.3; p =
      0.17). CONCLUSIONS: The use of prophylactic topical antibiotics following
      intravitreal injection may lead to higher rates of antibiotic-resistant bacteria
      in culture-positive endophthalmitis cases.

PMID- 25940560
TI  - Substrate geometry controls the cyclization cascade in multiproduct terpene
      synthases from Zea mays.
AB  - Multiproduct terpene synthases TPS4-B73 and TPS5-Delprim from maize (Zea mays)
      catalyze the conversion of farnesyl diphosphate (FDP) and geranyl diphosphate
      (GDP) into a complex mixture of sesquiterpenes and monoterpenes, respectively.
      Various isotopic and geometric isomers of natural substrates like (2Z)-[2-(2)H]-
      and [2,4,4,9,9,9-(2)H6]-(GDP) and (2Z,6E)-[2-(2)H]- and [2,4,4,13,13,13-(2)H6]
      (FDP) were synthesized analogous to presumptive reaction intermediates. On
      incubation with labeled (2Z) substrates, TPS4 and TPS5 showed much lower kinetic
      isotope effects than the labeled (2E) substrates. Interestingly, the products
      arising from the deuterated (2Z)-precursors revealed a distinct preference for
      cyclic products and exhibited an enhanced turnover on comparison with natural
      (2E)-substrates. This increase in the efficiency due to (2Z) configuration
      emphasizes the rate limiting effect of the initial (2E) -> (2Z) isomerization
      step in the reaction cascade of the multiproduct terpene synthases. Apart from
      turnover advantages, these results suggest that substrate geometry can be used as
      a tool to optimize the biosynthetic reaction cascade towards valuable cyclic
      terpenoids. 

PMID- 25940561
TI  - Acute kidney injury in cardiac surgery patients receiving hydroxyethyl starch
      solutions.

PMID- 25940562
TI  - HTT-DB: horizontally transferred transposable elements database.
AB  - MOTIVATION: Horizontal transfer of transposable (HTT) elements among eukaryotes
      was discovered in the mid-1980s. As then, >300 new cases have been described. New
      findings about HTT are revealing the evolutionary impact of this phenomenon on
      host genomes. In order to provide an up to date, interactive and expandable
      database for such events, we developed the HTT-DB database. RESULTS: HTT-DB
      allows easy access to most of HTT cases reported along with rich information
      about each case. Moreover, it allows the user to generate tables and graphs based
      on searches using Transposable elements and/or host species classification and
      export them in several formats. AVAILABILITY AND IMPLEMENTATION: This database is
      freely available on the web at
      http://lpa.saogabriel.unipampa.edu.br:8080/httdatabase. HTT-DB was developed
      based on Java and MySQL with all major browsers supported. Tools and software
      packages used are free for personal or non-profit projects. CONTACT:
      bdotto82@gmail.com or gabriel.wallau@gmail.com.

PMID- 25940563
TI  - Phylesystem: a git-based data store for community-curated phylogenetic estimates.
AB  - MOTIVATION: Phylogenetic estimates from published studies can be archived using
      general platforms like Dryad (Vision, 2010) or TreeBASE (Sanderson et al., 1994).
      Such services fulfill a crucial role in ensuring transparency and reproducibility
      in phylogenetic research. However, digital tree data files often require some
      editing (e.g. rerooting) to improve the accuracy and reusability of the
      phylogenetic statements. Furthermore, establishing the mapping between tip labels
      used in a tree and taxa in a single common taxonomy dramatically improves the
      ability of other researchers to reuse phylogenetic estimates. As the process of
      curating a published phylogenetic estimate is not error-free, retaining a full
      record of the provenance of edits to a tree is crucial for openness, allowing
      editors to receive credit for their work and making errors introduced during
      curation easier to correct. RESULTS: Here, we report the development of software
      infrastructure to support the open curation of phylogenetic data by the community
      of biologists. The backend of the system provides an interface for the standard
      database operations of creating, reading, updating and deleting records by making
      commits to a git repository. The record of the history of edits to a tree is
      preserved by git's version control features. Hosting this data store on GitHub
      (http://github.com/) provides open access to the data store using tools familiar
      to many developers. We have deployed a server running the 'phylesystem-api',
      which wraps the interactions with git and GitHub. The Open Tree of Life project
      has also developed and deployed a JavaScript application that uses the
      phylesystem-api and other web services to enable input and curation of published
      phylogenetic statements. AVAILABILITY AND IMPLEMENTATION: Source code for the web
      service layer is available at https://github.com/OpenTreeOfLife/phylesystem-api.
      The data store can be cloned from: https://github.com/OpenTreeOfLife/phylesystem.
      A web application that uses the phylesystem web services is deployed at
      http://tree.opentreeoflife.org/curator. Code for that tool is available from
      https://github.com/OpenTreeOfLife/opentree. CONTACT: mtholder@gmail.com.

PMID- 25940564
TI  - Transthyretin deposition in articular cartilage: a novel mechanism in the
      pathogenesis of osteoarthritis.
AB  - OBJECTIVE: Amyloid deposits are prevalent in osteoarthritic (OA) joints. We
      undertook this study to define the dominant precursor and to determine whether
      the deposits affect chondrocyte functions. METHODS: Amyloid deposition in human
      normal and OA knee cartilage was determined by Congo red staining. Transthyretin
      (TTR) in cartilage and synovial fluid was analyzed by immunohistochemistry and
      Western blotting. The effects of recombinant amyloidogenic and nonamyloidogenic
      TTR variants were tested in human chondrocyte cultures. RESULTS: Normal cartilage
      from young donors did not contain detectable amyloid deposits, but 7 of 12 aged
      normal cartilage samples (58%) and 12 of 12 OA cartilage samples (100%) had Congo
      red staining with green birefringence under polarized light. TTR, which is
      located predominantly at the cartilage surfaces, was detected in all OA cartilage
      samples and in a majority of aged normal cartilage samples, but not in normal
      cartilage samples from young donors. Chondrocytes and synoviocytes did not
      contain significant amounts of TTR messenger RNA. Synovial fluid TTR levels were
      similar in normal and OA knees. In cultured chondrocytes, only an amyloidogenic
      TTR variant induced cell death as well as the expression of proinflammatory
      cytokines and extracellular matrix-degrading enzymes. The effects of
      amyloidogenic TTR on gene expression were mediated in part by Toll-like receptor
      4, receptor for advanced glycation end products, and p38 MAPK. TTR-induced
      cytotoxicity was inhibited by resveratrol, a plant polyphenol that stabilizes the
      native tetrameric structure of TTR. CONCLUSION: These findings are the first to
      suggest that TTR amyloid deposition contributes to cell and extracellular matrix
      damage in articular cartilage in human OA and that therapies designed to reduce
      TTR amyloid formation might be useful.

PMID- 25940565
TI  - Computational simulation: astrocyte-induced depolarization of neighboring neurons
      mediates synchronous UP states in a neural network.
AB  - Although recent reports have suggested that synchronous neuronal UP states are
      mediated by astrocytic activity, the mechanism responsible for this remains
      unknown. Astrocytic glutamate release synchronously depolarizes adjacent neurons,
      while synaptic transmissions are blocked. The purpose of this study was to
      confirm that astrocytic depolarization, propagated through synaptic connections,
      can lead to synchronous neuronal UP states. We applied astrocytic currents to
      local neurons in a neural network consisting of model cortical neurons. Our
      results show that astrocytic depolarization may generate synchronous UP states
      for hundreds of milliseconds in neurons even if they do not directly receive
      glutamate release from the activated astrocyte. 

PMID- 25940566
TI  - Estrogen modulation properties of mangiferin and quercetin and the mangiferin
      metabolite norathyriol.
AB  - Mango fruit contain many bioactive compounds, some of which are transcription
      factor regulators. Estrogen receptor alpha (ERalpha) and beta (ERbeta) are two
      regulators of gene transcription that are important in a variety of physiological
      processes and also in diseases including breast cancer. We examined the ability
      of the mango constituents quercetin, mangiferin, and the aglycone form of
      mangiferin, norathyriol, to activate both isoforms of the estrogen receptor.
      Quercetin and norathyriol decreased the viability of MCF-7 breast cancer cells
      whereas mangiferin had no effect on MCF-7 cells. We also determined that
      quercetin and mangiferin selectively activated ERalpha whereas norathyriol
      activated both ERalpha and ERbeta. Despite quercetin, mangiferin and norathyriol
      having similar polyphenolic structural motifs, only norathyriol activated ERbeta,
      showing that bioactive agents in mangoes have very specific biological effects.
      Such specificity may be important given the often-opposing roles of ERalpha and
      ERbeta in breast cancer proliferation and other cellular processes.

PMID- 25940567
TI  - Answer to the Letter to the Editor of G. Liao et al. concerning "Is tranexamic
      acid effective and safe in spinal surgery? A meta-analysis of randomized
      controlled trials" by Li ZJ, Fu X, Xing D, Zhang HF, Zang JC, Ma XL (2013) Eur
      Spine J 22(9):1950-7.

PMID- 25940568
TI  - Zoledronic acid-loaded bone cement as a local adjuvant therapy for giant cell
      tumor of the sacrum after intralesional curettage.
AB  - PURPOSE: Giant cell tumor of the sacrum is usually silent in initial stages and
      not diagnosed until achieving a large size. Intralesional curettage of the tumor
      has lower risk of neurological damage but is with high recurrence rate.
      Zoledronic acid-loaded cement was demonstrated to have cytotoxic effect on the
      cell line of giant cell tumor. This study evaluate if zoledronic acid-loaded bone
      cement would reduce the recurrence rate of sacral giant cell tumor after
      intralesional curettage. METHODS: Four patients were diagnosed as sacral giant
      cell tumor and received intralesional curettage with placement of zoledronic acid
      loaded bone cement for adjuvant local control. The clinical records including
      tumor location, tumor size, complication, follow-up status, and functional
      outcome were analyzed retrospectively. RESULTS: All four patients presented with
      cauda equina syndrome before surgery with mean tumor volume of 472.8 cm(3). With
      placement of zoledronic acid-loaded cement, no local recurrence was observed
      during the mean follow-up period of 28 months. All patients were found to have
      new bone regeneration on radiograph. All patients suffering from cauda equina
      syndrome were recovered. CONCLUSIONS: We suggested that placement of zoledronic
      acid-loaded bone cement was an effective adjuvant therapy for sacral giant cell
      tumor following intralesional curettage.

PMID- 25940569
TI  - Self-monitoring of blood glucose for type 2 diabetes 2.

PMID- 25940570
TI  - CT Signs Can Predict Treatment Response and Long-Term Survival: A Study in
      Locally Advanced Esophageal Cancer with Preoperative Chemotherapy.
AB  - BACKGROUND: Accurate prediction of treatment response and prognosis before
      surgery allows prompt therapy adjustment. This study aimed to evaluate the
      efficacy of computed tomography (CT) signs in predicting treatment response and
      survival for advanced esophageal squamous cell carcinoma patients who received
      preoperative chemotherapy. METHODS: This study retrospectively enrolled 135
      consecutive patients with preoperative chemotherapy from September 2005 to
      December 2011. A logistic regression model was used to evaluate the association
      between pathologic response and CT signs. Overall survival (OS) and disease-free
      survival (DFS) were estimated using the Kaplan-Meier method, and a Cox
      proportional hazards model was constructed to determine associations between CT
      signs after neoadjuvant chemotherapy and survival outcomes. RESULTS: Logistic
      regression showed that the significant predictors of a poor response were the
      total number of lymph nodes (LNs) (>6) at baseline [odds ratio (OR) 5.07; 95 %
      confidence interval (CI) 1.86-13.81; P = 0.002] and the CT value change rate
      (<=17 %) (OR 2.35; 95 % CI 1.05-5.23; P = 0.037). In the Cox analyses, the
      significant predictors of OS were preoperative tumor thickness (>10 mm) [hazard
      ratio (HR) 2.33; 95 % CI 1.36-4; P = 0.002), total number of LNs (>6) (HR 1.88;
      95 % CI 1.12-3.17; P = 0.017), and short diameter of the largest LN (>10 mm) (HR
      1.87; 95 % CI 1.07-3.28; P = 0.028), whereas only the short diameter of the
      largest LN was a significant predictor of DFS (HR 2.36; 95 % CI 1.23-4.54; P =
      0.01). CONCLUSIONS: CT signs can predict therapeutic efficacy and survival
      outcomes and provide an opportunity to offer additional treatment options before
      surgery.

PMID- 25940571
TI  - Older Age is Associated with a Higher Incidence of Melanoma Death but a Lower
      Incidence of Sentinel Lymph Node Metastasis in the SEER Databases (2003-2011).
AB  - PURPOSE: Elderly melanoma patients are known to have lower survival rates than
      younger patients with melanoma. Paradoxically, a few recent studies have shown a
      lower frequency of sentinel lymph node (SLN) positivity in older individuals.
      This is the first analysis of a large national sample to examine the relationship
      between SLN metastasis and melanoma death across all age groups. METHODS: The
      U.S. Surveillance Epidemiology and End Results (SEER) Databases were queried to
      examine SLN biopsy and mortality outcomes in 158,813 melanoma cases reported from
      2003 to 2011, the most current data available in SEER. RESULTS: In bivariate
      analyses of the 47,577 cases with coded tumor depths and nodal surgery,
      increasing age varied directly with melanoma death and inversely with SLN
      positivity, for tumor depths >1 mm (P < 0.001). In multivariate regression
      analyses, 60-79 year-olds were more likely to die of melanoma compared with 20-39
      year-olds [odds ratio (OR) 1.83, 95 % confidence interval (CI) 1.64-2.05], but
      they were less likely to be SLN-positive (OR 0.62, 95 % CI 0.57-0.68). The
      inverse association between melanoma mortality and SLN positivity was most
      pronounced at the extremes of age. DISCUSSION: The finding that increasing age is
      associated with a higher incidence of melanoma death but a lower incidence of SLN
      metastasis highlights the need for further study into age-related differences in
      melanoma biology, immunological surveillance, and host response. It also
      questions whether the 5- and 10-year survival rates associated with the current
      melanoma staging system should be stratified by age to predict outcomes more
      accurately for melanoma patients.

PMID- 25940572
TI  - The effect of wrist surgery on the kinematic consistency of joint axis
      reconstruction in a static posture.
AB  - Three-dimensional analysis of wrist motion is a growing focus in orthopedic
      research, however, our understanding of its validity (accuracy and reliability)
      remains limited. Nine human cadavers were tested to estimate wrist joint axes
      alignment in a postural static pose. The objective was to investigate a rater's
      ability to reliably align three skin- tracked wrist joint coordinate system
      (WJCS) definitions across baseline and reconstructive wrist states (intact, mid
      carpal arthrodesis, and proximal-row carpectomy). Two WJCSs (legacy, anatomic)
      were based on palpated bony landmarks and the third (functional) was based on
      both landmarks and passive flexion-extension motion. A coordinate frame based on
      the anatomic definition was tracked with bone pins and served as a reference.
      Each WJCS was tested in each wrist state and in three forearm position (45
      degrees  pronation, neutral, 45 degrees  supination). The angular offset about
      each axis of the WJCS frames were calculated with respect to the reference in
      flexion-extension, radial-ulnar deviation, and pronation-supination for every
      iteration. Reliability and root mean square deviation values were analyzed across
      wrist states. Our data suggest that no WJCS is uniformly more reliable than
      another. The functional WJCS definition was most consistent across intact and
      post-operative states for pronation-supination offset, but this was dependent on
      rater interpretation. It still however offers the practical benefit of requiring
      fewer landmarks.

PMID- 25940573
TI  - Constitutive activation of Stat3 in mouse epidermis is linked to hair deficiency
      and cytoskeletal network damage.

PMID- 25940576
TI  - Relationship between seminal plasma tuberoinfundibular peptide of 39 residues and
      sperm functional attributes in buffalo (Bubalus bubalis).
AB  - The buffalo seminal plasma protein profile and its relationship with sperm
      quality have not been studied in detail. Thus, the aim of the present study was
      to profile buffalo seminal plasma proteins and to assess the relationship between
      differentially expressed proteins and sperm characteristics. Semen samples (n =
      44) were collected from 11 Murrah buffalo bulls (four ejaculates from each
      animal) and seminal plasma protein profiling was performed by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis. Matrix-assisted laser desorption
      ionisation time-of-flight analysis of one of the differentially expressed
      proteins, namely the 11-12 kDa protein, identified it as tuberoinfundibular
      peptide of 39 residues (TIP39). Western blot analysis confirmed the presence of
      TIP39, with TIP39 expression in seminal plasma varying among bulls. Based on
      TIP39 levels, bulls were classified into two groups, those with high and low
      protein. The percentages of spermatozoa positive for mitochondrial membrane
      potential test, chromatin distribution test, synthetic media sperm penetrability
      test and acrosomal integrity test were significantly (P < 0.05) high in the high
      protein group. The present study is the first to demonstrate the presence of
      TIP39 in buffalo seminal plasma and the positive effect of TIP39 on the
      functional parameters and fertilising ability of spermatozoa.

PMID- 25940575
TI  - Malignancy-associated haemophagocytic lymphohistiocytosis in children and
      adolescents.
AB  - Haemophagocytic lymphohistiocytosis (HLH) in the context of malignancy is mainly
      considered a challenge of adult haematology. While this association is also
      observed in children, little is known regarding inciting factors, appropriate
      treatment and prognosis. We retrospectively analysed 29 paediatric and adolescent
      patients for presenting features, type of neoplasm or preceding chemotherapy,
      treatment and outcome. Haemophagocytic lymphohistiocytosis was considered
      triggered by the malignancy (M-HLH) in 21 patients, most of whom had T- (n = 12)
      or B-cell neoplasms (n = 7), with Epstein-Barr virus as a co-trigger in five
      patients. In eight patients, HLH occurred during chemotherapy (Ch-HLH) for
      malignancy, mainly acute leukaemias (n = 7); an infectious trigger was found in
      seven. In M- and Ch-HLH, median overall survival was 1.2 and 0.9 years, and the 6
      month survival rates were 67% and 63%, respectively. Seven of 11 deceased M-HLH
      patients exhibited active malignancy and HLH at the time of death, while only two
      out of five deceased Ch-HLH patients had evidence of active HLH. To overcome HLH,
      malignancy- and HLH-directed treatments were administered in the M-HLH cohort;
      however, it was not possible to determine superiority of one approach over the
      other. For Ch-HLH, treatment ranged from postponement of chemotherapy to the use
      of etoposide-containing regimens. 

PMID- 25940577
TI  - Risk of catecholaminergic crisis following glucocorticoid administration in
      patients with an adrenal mass: a literature review.
AB  - BACKGROUND: Glucocorticoids as diagnostic or therapeutic agents have been
      reported to carry an increased risk of catecholaminergic crisis (CC) in patients
      with pheochromocytoma or paraganglioma (PPGL). METHODS: We searched literature
      databases using the following terms: pheochromocytoma, paraganglioma, adrenal
      incidentaloma, steroids, glucocorticoids, dexamethasone suppression test (DST),
      hypertensive crisis, cosyntropin and CRH. From all published case reports (1962
      2013), we reviewed medical history, presenting symptoms, dose and route of
      steroid administration, location and size of adrenal mass, biochemical phenotype
      and outcome. RESULTS: Twenty-five case reports describing a CC were identified.
      Three patients with an adrenal incidentaloma suffered a CC following high-dose
      DST, and in one case, this was fatal. In two of these patients, biochemical
      testing missed the diagnosis, and in the third, a DST was done despite elevated
      urinary metanephrines. No CC has been reported for patients undergoing a low-dose
      DST. Three of 16 patients who received therapeutic glucocorticoids and four of
      six patients following cosyntropin testing died. No specific biochemical
      phenotype was related to adverse events. CONCLUSIONS: Although a causal
      relationship cannot be established from this review, it seems prudent to exclude
      a PPGL in patients with a large incidentaloma or when high-dose DST is considered
      in a patient with an incidentaloma of any size. Our literature review does not
      support the need for biochemical testing for PPGL prior to a low-dose (1 mg) DST.
      Finally, before starting therapeutic glucocorticoids, any clinical signs or
      symptoms of a potential PPGL should prompt reliable biochemical testing to rule
      out a PPGL.

PMID- 25940578
TI  - Productivity at work and quality of life in patients with rheumatoid arthritis.
AB  - BACKGROUND: The aim of this study was to determine which combination of personal,
      disease-related and environmental factors is best associated with at-work
      productivity loss in patients with rheumatoid arthritis (RA), and to determine
      whether at-work productivity loss is associated with the quality of life for
      these patients. METHODS: This study is based on cross-sectional data. Patients
      completed a questionnaire with personal, disease-related and environmental
      factors (related to the work environment), and clinical characteristics were
      obtained from patient medical records. At-work productivity loss was measured
      with the Work Limitations Questionnaire, and quality of life with the RAND 36.
      Using linear regression analyses, a multivariate model was built containing the
      combination of factors best associated with at-work productivity loss. This model
      was cross-validated internally. We furthermore determined whether at-work
      productivity loss was associated with quality of life using linear regression
      analyses. RESULTS: We found that at-work productivity loss was associated with
      workers who had poorer mental health, more physical role limitations, were ever
      treated with a biological therapeutic medication, were not satisfied with their
      work, and had more work instability (R(2) = 0.50 and R(2) following cross
      validation was 0.32). We found that at-work productivity loss was negatively
      associated with health-related quality of life, especially with dimensions of
      mental health, physical role limitations, and pain. CONCLUSIONS: We found that at
      work productivity loss was associated with personal, work-related, and clinical
      factors. Although our study results should be interpreted with caution, they
      provide insight into patients with RA who are at risk for at-work productivity
      loss.

PMID- 25940579
TI  - Safety of nonsteroidal antiinflammatory drugs in patients with cardiovascular
      disease.
AB  - Nonsteroidal antiinflammatory drugs (NSAIDs) are used in the management of a
      variety of conditions, but their prevalence is likely underreported as a result
      of widespread availability and the perception that nonprescription therapies are
      unnecessary to report during medication history taking. However, NSAIDs are
      associated with a number of adverse effects, especially in patients with
      cardiovascular disease (CVD). Patients with CVD and comorbidities for which
      NSAIDs may provide symptomatic relief (e.g., osteoarthritis, rheumatoid
      arthritis) tend to be older, which places them at greater risk of harm. For these
      reasons, the use of NSAIDs in patients with CVD is a significant public health
      concern. An understanding of the risks associated with NSAIDs is critical for
      clinicians across practice settings. In this review, we detail the safety of
      NSAIDs in patients with CVD, provide recommendations on their use in specific
      disease states, and discuss therapeutic alternatives. 

PMID- 25940580
TI  - Increase of serotypes 15A and 23B in IPD in Germany in the PCV13 vaccination era.
AB  - BACKGROUND: This study presents an analysis of 1,491 serogroup 23 and 762
      serogroup 15 isolates from invasive pneumococcal disease (IPD) in children and
      adults before and after the general recommendation for childhood pneumococcal
      conjugate vaccination in Germany in July 2006. Vaccination formulations used were
      PCV7 (from July 2006), PCV10 (from April 2009) and PCV13 (from December 2009,
      replacing PCV7). METHODS: The German National Reference Center for Streptococci
      (GNRCS) has conducted surveillance of IPD since 1992. Isolates were serotyped and
      tested for antibiotic susceptibility. Selected isolates were characterized using
      MLST. RESULTS: In an analysis of 23,957 isolates from IPD in children and adults
      sent to the GNRCS between July 1992 and June 2014, we found a strongly
      significant increase of non-PCV13 serotypes in the late vaccination (PCV13)
      period (2010-2014). Among these, the proportions of serotypes 15A and 23B were
      the most strongly significantly increasing. After the recommendation for
      pneumococcal conjugate childhood vaccination in 2006 and the introduction of
      higher-valent vaccines in 2009, the proportion of 15A increased significantly
      from 0.5% in the early vaccination period (2007-2010) to 2.4% in the late
      vaccination period (2010-2014, p=3.14 x 10(-22)). The proportion of serotype 23B
      increased from 0.5% to 2.8% in the same period (p=1.55 x 10(-29)). Penicillin non
      susceptibility levels of the serotype 15A (47.4%) and serotype 23B (46.5%)
      isolates were high, with MIC values ranging from 0.12-2 MUg/ml (15A) and 0.12-0.5
      MUg/ml (23B). MLSTs of serotype 23B isolates grouped in two clonal complexes
      (CC): CC439, with sequence type (ST) 439 as the main representative and CC338
      (linked to CC156), with ST1349 as most prevalent clone. Both CCs have been
      present over almost the whole surveillance period. All penicillin non-susceptible
      isolates occurred in CC338. Serotype 15A isolates appeared to be more diverse.
      Six CCs, one group of three STs and two singletons were found among 20 isolates.
      Most prevalent was CC63, with ST63 as most prominent representative (n=5). Most
      penicillin non-susceptible isolates were found among CC63 isolates. CONCLUSIONS:
      The prevalence of non-PCV13 serotypes in Germany has increased significantly
      between July 2007 and June 2014, with 15A and 23B being the most strongly
      increasing serotypes of all. Both serotypes show a high proportion of penicillin
      non-susceptibility.

PMID- 25940581
TI  - Influence of Tonsillar Size on OSA Improvement in Children Undergoing
      Adenotonsillectomy.
AB  - OBJECTIVE: To determine if pediatric obstructive sleep apnea (OSA) improves after
      adenotonsillectomy (AT) regardless of tonsil size. STUDY DESIGN: Case series with
      chart review. SETTING: Pediatric Otolaryngology Department, Johns Hopkins
      Hospital. SUBJECTS: Seventy children 1 to 18 years of age who underwent
      polysomnography (PSG) before and after AT. METHODS: Tonsil size was evaluated
      using the Brodsky grading scale. RESULTS: Children were stratified by tonsil size
      as 2+ (n = 20), 3+ (n = 36), and 4+ (n = 14). There was a significant improvement
      in obstructive apnea-hypopnea index (oAHI), apnea index (AI), and saturation
      nadir across all 3 groups after AT. Preoperative oAHI, AI, and hypopnea index
      (HI) were similar regardless of tonsil size (P > .05). Overall, oAHI improved
      from a median of 11.8 +/- 21.7 to 2.0 +/- 6.1 events/h, with 40% (28/70) of
      children having complete resolution. The oAHI (P < .0001-0.02), AI (P < .0001
      0.017), HI (P < .0001-0.058), and saturation nadir (P < .0001-0.017)
      significantly improved for the 2+, 3+, and 4+ groups. Only the HI (P = .058) in
      the 2+ group did not. The median oAHI improvement was 3.4 +/- 26.4 events/h in
      the 2+ group, 8.3 +/- 16.6 events/h in the 3+ group, and 12.3 +/- 19.5 events/h
      in the 4+ group, with 25% (5/20), 50% (18/36), and 36% (5/14), respectively,
      having complete resolution. There was no correlation between OSA severity and
      tonsil or adenoid size (P > .32). CONCLUSION: Tonsil size did not correlate with
      OSA severity. While a larger proportion of patients classified as 3+ and 4+ had
      complete resolution after surgery, significant improvement was seen in AI and
      saturation nadir even in those classified as 2+.

PMID- 25940582
TI  - Registered Nurses and Discharge Planning in a Taiwanese ED: A Neglected Issue?
AB  - Published research on discharge planning is written from the perspective of
      hospital wards and community services. Limited research focuses on discharge
      planning in the emergency department (ED). The objective of this study was to
      identify ED nurses' perceptions of factors influencing the implementation of
      discharge planning. This qualitative study collected data from 25 ED nurses
      through in-depth interviews and a drawing task in which participants were asked
      to depict on paper the implementation of discharge planning in their practice.
      Factors influencing discharge planning were grouped into three categories:
      discharge planning as a neglected issue in the ED, heavy workload, and the
      negative attitudes of ED patients and their families. The study highlighted a
      need for effective discharge planning to be counted as an essential clinical
      competency for ED nurses and factored into their everyday workload. Nurses
      perceived that organizational culture, and parents' and relatives' attitudes were
      barriers to implementing discharge teaching in the ED.

PMID- 25940584
TI  - Transient Left Septal Fascicular Block: An Electrocardiographic Expression of
      Proximal Obstruction of Left Anterior Descending Artery?

PMID- 25940585
TI  - A cost minimization analysis of early correction of anterior crossbite-a
      randomized controlled trial.
AB  - OBJECTIVE: Economic evaluations provide an important basis for allocation of
      resources and health services planning. The aim of this study was to evaluate and
      compare the costs of correcting anterior crossbite with functional shift, using
      fixed or removable appliances (FA or RA) and to relate the costs to the effects,
      using cost-minimization analysis. DESIGN, SETTING, AND PARTICIPANTS: Sixty-two
      patients with anterior crossbite and functional shift were randomized in blocks
      of 10. Thirty-one patients were randomized to be treated with brackets and arch
      wire (FA) and 31 with an acrylic plate (RA). Duration of treatment and number and
      estimated length of appointments and cancellations were registered. Direct costs
      (premises, staff salaries, material, and laboratory costs) and indirect costs
      (the accompanying parents' loss of income while absent from work) were calculated
      and evaluated with reference to successful outcome alone, to successful and
      unsuccessful outcomes and to re-treatment when required. Societal costs were
      defined as the sum of direct and indirect costs. INTERVENTIONS: Treatment with FA
      or RA. RESULTS: There were no significant differences between FA and RA with
      respect to direct costs for treatment time, but both indirect costs and direct
      costs for material were significantly lower for FA. The total societal costs were
      lower for FA than for RA. LIMITATIONS: Costs depend on local factors and should
      not be directly extrapolated to other locations. CONCLUSION: The analysis
      disclosed significant economic benefits for FA over RA. Even when only successful
      outcomes were assessed, treatment with RA was more expensive. TRIAL REGISTRATION:
      This trial was not registered. PROTOCOL: The protocol was not published before
      trial commencement.

PMID- 25940586
TI  - Molecular characterization of hepatitis C virus for determination of subtypes and
      detection of resistance mutations to protease inhibitors in a group of
      intravenous drug users co-infected with HIV.
AB  - Modifications in therapeutic regimens for the treatment of hepatitis C virus
      (HCV) have been observed since the approval of viral protease inhibitors (PI),
      and the selection of natural drug-resistant variants has been also reported.
      Thus, it becomes crucial to be aware of consequences of new therapeutic
      approaches and make available tools for monitoring the infection. The study aimed
      to apply an "in-house" method for amplification and sequencing of the NS3 region
      which is the target of PI, and allowing simultaneously the classification of
      viral subtypes and identification of resistance mutations. Forty-seven samples
      collected from HIV injecting drug users and drug naive for HCV protease
      inhibitors were tested for anti-HCV antibodies, 93.6% of them had a positive
      result and in 70.5% was determined HCV active infection. High frequency of
      subtype 1a (46.2%), followed by an equal proportion of subtypes 3a, 4a, and 4d
      (15.4%) was obtained. Two potential recombinants, RF1_2k/1b (3.8%) and 2q/2k
      (3.8%) were identified. Substitutions V36L/P, T54A, I72L/N/T/V, Q80K/G, S122R/T,
      D168Q, and I170L/V were observed in 65.4% of the samples. The T54A and Q80K
      mutations, and the combination V36L + T54A were also identified. Polymorphisms
      were observed exclusively associated with specific genotypes, particularly, I72L
      and D168Q with genotype 3, and S122T with genotype 4. The V36L substitution was
      identified in 92.8% of sequences of non-genotype 1 denoting that this amino acid
      substitution is a natural polymorphism associated with non-genotype 1 strains.
      Although no major PI resistance mutations were detected, a more extensive study
      is needed to evaluate the impact of mutations identified in efficacy of PI
      treatment.

PMID- 25940588
TI  - Discovery of an NRF1-specific inducer from a large-scale chemical library using a
      direct NRF1-protein monitoring system.
AB  - NRF1 (NF-E2-p45-related factor 1) plays an important role in the regulation of
      genes encoding proteasome subunits, a cystine transporter, and lipid-metabolizing
      enzymes. Global and tissue-specific disruptions of the Nrf1 gene in mice result
      in embryonic lethality and spontaneous development of severe tissue defects,
      respectively, suggesting NRF1 plays a critical role in vivo. Mechanistically, the
      continuous degradation of the NRF1 protein by the proteasome is regarded as a
      major regulatory nexus of NRF1 activity. To develop NRF1-specific inducers that
      act to overcome the phenotypes related to the lack of NRF1 activity, we
      constructed a novel NRF1DeltaC-Luc fusion protein reporter and developed cell
      lines that stably express the reporter in Hepa1c1c7 cells for use in high
      throughput screening. In screening of a chemical library with this reporter
      system, we identified two hit compounds that significantly induced luciferase
      activity. Through an examination of a series of derivatives of one of the hit
      compounds, we identified T1-20, which induced a 70-fold increase in luciferase
      activity. T1-20 significantly increased the level of NRF1 protein in the mouse
      liver, indicating that the compound is also functional in vivo. Thus, these
      results show the successful identification of the first small chemical compounds
      which specifically and significantly induce NRF1.

PMID- 25940589
TI  - Biomass Yield and Steviol Glycoside Production in Callus and Suspension Culture
      of Stevia rebaudiana Treated with Proline and Polyethylene Glycol.
AB  - Enhanced production of steviol glycosides (SGs) was observed in callus and
      suspension culture of Stevia rebaudiana treated with proline and polyethylene
      glycol (PEG). To study their effect, yellow-green and compact calli obtained from
      in vitro raised Stevia leaves were sub-cultured on MS medium supplemented with
      2.0 mg l(-1) NAA and different concentrations of proline (2.5-10 mM) and PEG (2.5
      10 %) for 2 weeks, and incubated at 24 +/- 1  degrees C and 22.4 MUmol m(-2) s(
      1) light intensity provided by white fluorescent tubes for 16 h. Callus and
      suspension culture biomass (i.e. both fresh and dry weight content) was increased
      with 5 mM proline and 5 % PEG, while at further higher concentrations, they got
      reduced. Further, quantification of SGs content in callus (collected at 15th day)
      and suspension culture (collected at 10th and 15th day) treated with and without
      elicitors was analysed by HPLC. It was observed that chemical stress enhanced the
      production of SGs significantly. In callus, the content of SGs increased from
      0.27 (control) to 1.09 and 1.83 % with 7.5 mM proline and 5 % PEG, respectively,
      which was about 4.0 and 7.0 times higher than control. However, in the case of
      suspension culture, the same concentrations of proline and polyethylene glycol
      enhanced the SG content from 1.36 (control) to 5.03 and 6.38 %, respectively, on
      10th day which were 3.7 times and 4.7 times higher than control. 

PMID- 25940587
TI  - Structural Brain Changes in Early-Onset Alzheimer's Disease Subjects Using the
      LONI Pipeline Environment.
AB  - BACKGROUND AND PURPOSE: This study investigates 36 subjects aged 55-65 from the
      Alzheimer's Disease Neuroimaging Initiative (ADNI) database to expand our
      knowledge of early-onset (EO) Alzheimer's Disease (EO-AD) using neuroimaging
      biomarkers. METHODS: Nine of the subjects had EO-AD, and 27 had EO mild cognitive
      impairment (EO-MCI). The structural ADNI data were parcellated using BrainParser,
      and the 15 most discriminating neuroimaging markers between the two cohorts were
      extracted using the Global Shape Analysis (GSA) Pipeline workflow. Then the Local
      Shape Analysis (LSA) Pipeline workflow was used to conduct local (per-vertex)
      post-hoc statistical analyses of the shape differences based on the participants'
      diagnoses (EO-MCI+EO-AD). Tensor-based Morphometry (TBM) and multivariate
      regression models were used to identify the significance of the structural brain
      differences based on the participants' diagnoses. RESULTS: The significant
      between-group regional differences using GSA were found in 15 neuroimaging
      markers. The results of the LSA analysis workflow were based on the subject
      diagnosis, age, years of education, apolipoprotein E (epsilon4), Mini-Mental
      State Examination, visiting times, and logical memory as regressors. All the
      variables had significant effects on the regional shape measures. Some of these
      effects survived the false discovery rate (FDR) correction. Similarly, the TBM
      analysis showed significant effects on the Jacobian displacement vector fields,
      but these effects were reduced after FDR correction. CONCLUSIONS: These results
      may explain some of the differences between EO-AD and EO-MCI, and some of the
      characteristics of the EO cognitive impairment subjects.

PMID- 25940590
TI  - Characterization and identification of iridoid glucosides, flavonoids and
      anthraquinones in Hedyotis diffusa by high-performance liquid
      chromatography/electrospray ionization tandem mass spectrometry.
AB  - The multiple bioactive constituents in Hedyotis diffusa Willd. (H. diffusa) were
      extracted and characterized by high-performance liquid
      chromatography/electrospray ionization tandem mass spectrometry (HPLC-ESI-MS(n)).
      The optimized separation condition was obtained using an Agilent ZorBax SB-C18
      column (4.6*150 mm, 5 MUm) and gradient elution with water (containing 0.1%
      formic acid) and acetonitrile (containing 0.1% formic acid), under which baseline
      separation for the majority of compounds was achieved. Among the compounds
      detected, 14 iridoid glucosides, 10 flavonoids, 7 anthraquinones, 1 coumarin and
      1 triterpene were unambiguously identified or tentatively characterized based on
      their retention times and mass spectra in comparison with the data from standards
      or references. The fragmentation behavior for different types of constituents was
      also investigated, which could contribute to the elucidation of these
      constituents in H. diffusa. The present study reveals that even more iridoid
      glycosides were found in H. diffusa than hitherto assumed. The occurrence of two
      iridoid glucosides and five flavonoids in particular has not yet been described.
      This paper marks the first report on the structural characterization of chemical
      compounds in H. diffusa by a developed HPLC-ESI-MS(n) method. 

PMID- 25940591
TI  - Fibrosing mediastinitis complicating prior histoplasmosis is associated with
      human leukocyte antigen DQB1*04:02 - a case control study.
AB  - BACKGROUND: Fibrosing mediastinitis (FM) is an idiosyncratic reaction to
      infection with Histoplasma capsulatum with a prevalence of 3:100,000 people
      infected. The rarity of post-histoplasmosis fibrosing mediastinitis (PHFM) in
      areas where H. capsulatum is endemic suggests that an abnormal immunological host
      response may be responsible for the development of fibrosis. Our group previously
      reported an association between subjects with PHFM and human leukocyte antigen
      (HLA)-A*02. We sought to confirm or extend those findings with application of
      high resolution HLA typing in a cohort of subjects with PHFM. METHODS: High
      resolution HLA typing was performed on DNA samples from a new cohort 34 patients
      with PHFM. Control cohorts included 707 subjects from the "European American"
      subset of the National Marrow Donor Program((r)) (NMDP) and 700 subjects from
      Dialysis Clinic, Inc. (DCI). The carriage frequencies of the HLA alleles
      identified in the PHFM, NMDP, and DCI cohorts were calculated and then all were
      compared. RESULTS: We found an increase in the carriage frequency of HLA
      DQB1*04:02 in PHFM subjects relative to the controls (0.15 versus 0.07 in DCI and
      0.05 in NMDP; p = 0.08 and 0.03). Multiple logistic regression showed that
      DQB1*04:02 was statistically significant (p = 0.04), while DQB1*03:02 and C*03:04
      had point estimates of OR > 1, though they did not reach statistical
      significance. The HLA-A*02 association was not replicated. CONCLUSIONS: HLA
      DQB1*04:02 is associated with PHFM, which supports the premise that an aberrant
      host immune response contributes to the development of PHFM.

PMID- 25940592
TI  - MiR-940 inhibits hepatocellular carcinoma growth and correlates with prognosis of
      hepatocellular carcinoma patients.
AB  - Hepatocellular carcinoma (HCC) is among the leading causes of cancer-related
      death in China. Deregulation of microRNA (miRNA) contributes to HCC development
      by influencing cell growth, apoptosis, migration or invasion. It has been proved
      that miR-940 plays important roles in various cancers. Here we investigated the
      role of miR-940 in HCC. We found that miR-940 was remarkably decreased in HCC
      tissues and cell lines. Importantly, lower miR-940 expression in HCC tissues
      significantly correlated with the reduced patient's survival rate. Overexpression
      of miR-940 inhibited HCC cell line growth and induced cell apoptosis, and vice
      versa. Estrogen-related receptor gamma (ESRRG) was targeted by miR-940, and
      suppression of ESRRG inhibited HCC cell lines growth and induced cell apoptosis.
      In conclusion, we found that a lower level of miR-940 in HCC promoted cellular
      proliferation via ESRRG, which may lead to the short survival period of HCC
      patients. 

PMID- 25940593
TI  - Tautomerization-mediated molecular switching between six- and seven-membered
      rings stabilized by hydrogen bonding.
AB  - 1,3,4,6-Tetraketones typically undergo keto-enol tautomerism forming bis-enols
      stabilized by intramolecular hydrogen bonding in two six-membered rings. However,
      1,3,4,6-tetraketones derived from the terpene ketone camphor and norcamphor exist
      as isomers with two distinguishable modes of intramolecular hydrogen bonding,
      namely, the formation of six- or seven-membered rings. The structural
      requirements for this so far unknown behavior were investigated in detail by
      synthesis and comparison of structural analogues. Both isomers of such 1,3,4,6
      tetraketones were fully characterized in solution and in the solid state.
      Intriguingly, they slowly interconvert in solution by means of tautomerism
      rotation cascades, as was corroborated by DFT calculations. The influence of
      temperature and complexation with the transition metals Pd, Rh, and Ir on the
      interconversion process was investigated. 

PMID- 25940594
TI  - Looking up: Recent advances in understanding and treating peritoneal
      carcinomatosis.
AB  - Until recently, a diagnosis of peritoneal carcinomatosis was uniformly
      accompanied by a grim prognosis that was typically measured in weeks to months.
      Consequently, the management of carcinomatosis revolves largely around palliation
      of symptoms such as bowel obstruction, nausea, pain, fatigue, and cachexia. A
      prior lack of effective treatment options created the nihilistic view that
      currently exists and persists despite improvements in the efficacy of systemic
      therapy and the evolution of multimodality approaches including surgery and
      intraperitoneal chemotherapy. This article reviews the evolution and current
      state of treatment options for patients with peritoneal carcinomatosis. In
      addition, it highlights recent advances in understanding the molecular biology of
      carcinomatosis and the focus of current and future clinical trials. Finally, this
      article provides practical management options for the palliation of common
      complications of carcinomatosis. It is hoped that the reader will recognize that
      carcinomatosis is no longer an imminent death sentence and that through continued
      research and therapeutic innovation, clinicians can make an even greater impact
      on this form of metastatic cancer.

PMID- 25940595
TI  - Periaortic Fat Tissue: A Predictor of Cardiac Valvular Calcification,
      Malnutrition, Inflammation, and Atherosclerosis Components in Hemodialysis
      Patients.
AB  - Cardiac valvular calcification (CVC) in end-stage renal disease is shown to be a
      component of malnutrition, inflammation, atherosclerosis, calcification (MIAC)
      syndrome. Thoracic periaortic fat tissue (T-PAFT) is shown to be increased in
      patients with end-stage renal disease (ESRD), and has positive correlation with
      MIAC. Negative correlation between CVC and vitamin D is shown in hemodialysis
      (HD) patients. In this study, we investigated a relationship between body
      composition, T-PAFT, metabolic and inflammatory parameters, and CVC in HD
      patients. Seventy-six HD patients (49M) were included. CVC is defined as bright
      echoes of >1 mm on one or more cusps on echocardiography. Results were expressed
      as the number of calcified valves (0,1,2). Calcium, phosphorus, parathyroid
      hormone (PTH), C-reactive protein (CRP), albumin and 25-hydroxy vitamin D levels
      were studied from predialysis blood samples. T-PAFT was calculated using a method
      with manual definition of borders on images from multislice computed tomography.
      Basal metabolic rate, muscle mass, total and truncal fat mass were measured by
      bioimpedance analysis. There were 65.8% of patients who had CVC. Patients with
      CVC were older (63.5 +/- 14.6 +/- 17, P = 0.02). T-PAFT (1599 +/- 596, 739.7 +/-
      179 mm(2) , P = 0.001) and CRP (15.8 +/- 11; 11.1 +/- 13.2 mg/dL; P = 0.04) were
      higher in the group with CVC. T-PAFT had positive correlations with CRP, MIAC,
      body mass index (BMI) and number of calcified valves, negative correlation with
      left ventricular ejection fraction, and no correlation with albumin, calcium,
      phosphorus, and PTH. The logistic regression analysis revealed that T-PAFT was a
      significant predictor of CVC. In this study, T-PAFT showed a positive correlation
      with inflammation, CVC, and MIAC score in HD patients. T-PAFT was a significant
      predictor of CVC. 

PMID- 25940596
TI  - Detection of enterotoxigenic E. coli in hospitalised children with and without
      diarrhoea in Blantyre, Malawi.
AB  - BACKGROUND: Enterotoxigenic E. coli (ETEC) is an important cause of diarrhoea
      among children in developing countries. The burden of ETEC infection was
      investigated for the first time in children in Malawi. METHODS: Faecal samples
      obtained from children < 5 years of age hospitalised with diarrhoea in Blantyre,
      Malawi over a 10-year period (1997-2007) before introduction of the rotavirus
      vaccine were examined by PCR for ETEC heat-labile (LT) and heat-stable (STh and
      STp) enterotoxins. Children hospitalised without diarrhoea were enrolled over a 2
      year period as a comparison group. RESULTS: ETEC was detected in 205 (10.6%) of
      1941 children with diarrhoea. The most prevalent toxin type was STh (6.6%),
      followed by LT (2.1%) and STp (0.9%). ETEC infection was most prevalent in
      infants aged 6-11 months. Co-infection with rotavirus was common. ETEC was
      detected in 37 (7.3%) of 507 children without diarrhoea. CONCLUSION: The burden
      of ETEC infection in young Malawian children is substantial and should become a
      focus of diarrhoea prevention efforts in the post-rotavirus vaccine era.

PMID- 25940597
TI  - Chromatin remodelling and histone m RNA accumulation in bovine germinal vesicle
      oocytes.
AB  - Major remodelling of the chromatin enclosed within the germinal vesicle occurs
      towards the end of oocyte growth in mammals, but the mechanisms involved in this
      process are not completely understood. In bovine, four distinct stages of
      chromatin compaction-ranging from a diffused state (GV0) to a fully compacted
      configuration (GV3)-are linked to the gradual acquisition of developmental
      potential. To better understand the molecular events and to identify mRNA
      modulations occurring in the oocyte during the GV0-to-GV3 transition,
      transcriptomic analysis was performed with the EmbryoGENE microarray platform.
      The mRNA abundance of several genes decreased as chromatin compaction increased,
      which correlates with progressive transcriptional silencing that is
      characteristic of the end of oocyte growth. On the other hand, the abundance of
      some transcripts increased during the same period, particularly several histone
      gene transcripts from the H2A, H2B, H3, H4, and linker H1 family. In silico
      analysis predicted RNA-protein interactions between specific histone transcripts
      and the bovine stem-loop binding protein 2 (SLBP2), which helps regulate the
      translation of histone mRNA during oogenesis. These results suggest that some
      histone-encoding transcripts are actively stored, possibly to sustain the needs
      of the embryo before genome activation. This dataset offers a unique opportunity
      to survey which histone mRNAs are needed to complete chromatin compaction during
      oocyte maturation and which are stockpiled for the first three cell cycles
      following fertilization.

PMID- 25940598
TI  - Dwarf tapeworm (Hymenolepis nana): Characteristics in the Northern Territory 2002
      2013.
AB  - AIM: Review of dwarf tapeworm (Hymenolepis nana) presentations to Northern
      Territory (NT) Government health-care facilities over 12 years. We postulated H.
      nana infections would remain unchanged despite the introduction of deworming
      programmes as H. nana is not eradicated with albendazole treatment. METHODS: A
      retrospective observational analysis of consecutive microbiologically confirmed
      cases of H. nana identified by NT Government health-care facilities between 2002
      and 2013. RESULTS: Four hundred sixty-one episodes of H. nana infection were
      identified over the 12-year period from 68 387 faecal samples. Infections were
      overwhelmingly in young children with a median age of patients being 3.0 years
      (interquartile range 2.25-4.67). Patients were predominantly Indigenous (98.9%, P
      = 0.001) and infections occurred across the entire NT. Infections were associated
      with anaemia (18.2%) and eosinophilia (39.6%). The annual prevalence of NT
      Government health-care facility diagnosed H. nana infection remains relatively
      constant from 6.9 {4.8-9.0 (confidence interval (CI))} cases per 10 000
      Indigenous population in 2002, compared with 6.6 (4.7-8.4 CI) cases per 10 000
      Indigenous population in 2013. Infection rates in Indigenous children <5 years of
      age were: 46.1 (16.4-75.8 CI) cases/10 000 in 2002, compared with 44.3 (15.3-73.3
      CI) cases/10 000 Indigenous population in 2013. CONCLUSION: H. nana is the most
      frequently identified cestode (tapeworm) in NT Government health-care facilities.
      H. nana remains endemic throughout the NT, predominantly infecting Indigenous
      children less than 5 years of age.

PMID- 25940600
TI  - Participation in a clinical learning environment.

PMID- 25940599
TI  - Placental amino acid transport may be regulated by maternal vitamin D and vitamin
      D-binding protein: results from the Southampton Women's Survey.
AB  - Both maternal 25-hydroxyvitamin D (25(OH)D) concentrations during pregnancy and
      placental amino acid transporter gene expression have been associated with
      development of the offspring in terms of body composition and bone structure.
      Several amino acid transporter genes have vitamin D response elements in their
      promoters suggesting the possible linkage of these two mechanisms. We aimed to
      establish whether maternal 25(OH)D and vitamin D-binding protein (VDBP) levels
      relate to expression of placental amino acid transporters. RNA was extracted from
      102 placental samples collected in the Southampton Women's Survey, and gene
      expression was analysed using quantitative real-time PCR. Gene expression data
      were normalised to the geometric mean of three housekeeping genes, and related to
      maternal factors and childhood body composition. Maternal serum 25(OH)D and VDBP
      levels were measured by radioimmunoassay. Maternal 25(OH)D and VDBP levels were
      positively associated with placental expression of specific genes involved in
      amino acid transport. Maternal 25(OH)D and VDBP concentrations were correlated
      with the expression of specific placental amino acid transporters, and thus may
      be involved in the regulation of amino acid transfer to the fetus. The positive
      correlation of VDBP levels and placental transporter expression suggests that
      delivery of vitamin D to the placenta may be important. This exploratory study
      identifies placental amino acid transporters which may be altered in response to
      modifiable maternal factors and provides a basis for further studies. 

PMID- 25940601
TI  - Rosuvastatin improves hepatopulmonary syndrome through inhibition of inflammatory
      angiogenesis of lung.
AB  - The hepatopulmonary syndrome (HPS) is characterized by hypoxia and increased
      intrapulmonary shunts in cirrhotic patients. Emerging evidence showed promising
      results of treating HPS by abolishment of intrapulmonary inflammation and
      angiogenesis. Rosuvastatin is a kind of 3-hydroxy-methyl-3-glutamyl coenzyme A
      reductase inhibitor. In addition to lipid-lowering effects, it has anti
      inflammation and anti-angiogenesis properties. We postulated that rosuvastatin
      treatment can ameliorate HPS. Common bile duct ligation (CBDL) was applied in an
      experimental HPS animal model. CBDL rats received 2-week rosuvastatin (20
      mg/kg/day) treatments from the fifteenth day after operation. The haemodynamic
      data, blood gas analysis, liver biochemistries, tumour necrosis factor-alpha (TNF
      alpha) and vascular endothelial growth factor (VEGF) were examined after
      rosuvastatin treatment. The liver and lung tissues were dissected for
      histopathological studies and protein analyses. In the parallel groups,
      intrapulmonary shunts were determined. The haemodynamic and liver biochemistries
      were not changed after rosuvastatin treatment in CBDL rats, but the alveolar
      arterial oxygen pressure gradient was significantly decreased, implying that HPS
      induced hypoxia was reversed after rosuvastatin treatment. In addition,
      rosuvastatin treatment reduced intrapulmonary shunts and plasma levels of VEGF
      and TNF-alpha. Besides, the intrapulmonary protein expression of nuclear factor
      kappa B (NF-kappaB), VEGF receptor (VEGFR)-1,2 and Rho-associated A kinase were
      significantly down-regulated and the intrapulmonary angiogenesis was ameliorated.
      We concluded that rosuvastatin alleviates experimental HPS through blockade of
      pulmonary inflammatory angiogenesis via TNF-alpha/NF-kappaB and VEGF/Rho
      associated A kinase pathways down-regulation.

PMID- 25940602
TI  - Direct bone-to-bone integration between recombinant human bone morphogenetic
      protein-2-injected tendon graft and tunnel wall in an anterior cruciate ligament
      reconstruction model.
AB  - PURPOSE: This study was performed to evaluate one-stage anterior cruciate
      ligament (ACL) reconstruction using a semitendinosus tendon graft injected with
      bone morphogenetic protein 2 (BMP-2) in a rabbit model. METHODS: We injected
      recombinant human BMP-2 (rhBMP-2) in the experimental group and phosphate
      buffered saline in the control group at two sites of the semitendinosus tendon
      (15 MUg in each site) to replace tendon with bone in the bone tunnel. Twenty
      minutes later, the injected tendon graft was transplanted for ACL reconstruction
      by passing the graft through the bone tunnel. The animals were harvested at four,
      eight, or 12 weeks postoperatively and examined by histological and biomechanical
      methods. RESULTS: Histological analysis revealed that the tendon graft was
      replaced with new bone in the tunnel of the experimental group. Characteristic
      features identical to the regenerated direct insertion morphology at the bone
      tendon junction were acquired at eight or 12 weeks in the experimental group.
      Biomechanical pull-out testing revealed greater stiffness in the experimental
      than control group at 12 weeks, although the maximum load to failure showed no
      significant difference between the two groups at four, eight, or 12 weeks.
      CONCLUSION: These results indicate the potential for ACL reconstruction with
      regenerated direct insertion morphology.

PMID- 25940603
TI  - Evaluation of lengthening in reverse shoulder arthroplasty comparing X-rays and
      computerised tomography.
AB  - PURPOSE: The correct amount of arm lengthening in reverse shoulder arthroplasty
      is crucial to provide joint stability and good results. Determination has been
      proposed according to radiographs. However, radiographic measurements are error
      prone in regards to positioning of the arm with regard to the radiographic beam.
      The purpose of this study was to evaluate the precision of radiographic
      measurements compared to CT scans of the upper limb following reverse shoulder
      arthroplasty. METHODS: Thirty patients undergoing onlay reverse shoulder
      arthroplasty with comparative radiographs and CT scans of both humeri were
      included in this study. Arm length, humeral length as well as the arm and humeral
      lengthening were evaluated on pre- and postoperative radiographs compared to
      postoperative CT scans following a previously validated protocol. RESULTS: We
      found an excellent correlation for arm length and humeral length for radiographic
      and CT measurements (r > 0.90). The postoperative humeral and arm lengthening
      compared to the contralateral side was 0.1 (-1.2 to 1.2) cm and 2.8 (0.2 to 5.2)
      cm for the CT scans, and -0.6 (-4.1 to 2.0) cm and 1.9 (-2.3 to 5.0) cm for the
      radiographs. For arm lengthening, correlation coefficient was good (r = 0.7) even
      though radiographs indicated arm shortening in five cases whereas arm lengthening
      was observed on CT scans. CONCLUSIONS: Measurements on radiographs and CT scans
      are comparable in most of the cases. However, we observed some important
      variations that question the reliability of radiographic measurements in up to 20
      % of cases. Therefore, a CT scan appears to be necessary in the event of
      postoperative complications (e.g., instability, neurological problems).

PMID- 25940604
TI  - Feasibility and barriers of treating clubfeet in four countries.
AB  - PURPOSE: The purpose of this study was to elucidate why neglected clubfeet still
      exists despite the availability of a highly (cost)-effective treatment-the
      Ponseti treatment. METHODS: A qualitative and partly quantitative study with semi
      structured interviews was conducted in four countries: the Netherlands, South
      Africa, Argentina and Indonesia with both caregivers, mostly parents, of children
      with clubfoot and practitioners treating clubfoot. The topics discussed with the
      caregivers (n = 51) were the conceptions of the cause of clubfeet, received
      information, accessibility, financial aspects, and social stigma. With the
      practitioners (n = 11) the focus of the interviews was the treatment protocol and
      finance. RESULTS: Several barriers towards the start of the treatment were
      highlighted. At all places treatment was financed by the government, insurance or
      charity. Nevertheless, the cost of transport and missed working days formed a
      barrier, although there is a large difference between and within countries.
      Poverty, long travel duration, and beliefs of supernatural causes for the
      clubfoot result in delay in the start of treatment. CONCLUSION: These are
      problems we need to address when making effective treatment available for every
      child to diminish the burden of neglected clubfoot; especially accessible clinics
      in rural areas can be a good alternative to highly specialized hospitals in large
      cities. We as a community should try to find and overcome the barriers to treat
      these patients, because we have a relatively easy and highly cost-effective
      treatment option which can be given by trained non-physicians supervised by an
      interested medical doctor.

PMID- 25940605
TI  - Short-term outcomes of robotically assisted patello-femoral arthroplasty.
AB  - PURPOSE: The purpose of this study was to determine the outcomes in patients
      treated with robotically assisted patello-femoral arthroplasty (PFA). METHODS:
      This technique offers a safe, reliable, and reproducible way of obtaining correct
      implant positioning in patello-femoral arthroplasty, and as a result, reduces
      revision surgery due to implant malalignment. We evaluated 30 knees in 29
      patients who underwent robotically assisted patello-femoral arthroplasty between
      June 2009 and May 2011. Mean follow-up was 15.9 months. This was a retrospective
      study that involved chart reviews and radiographic analysis. Radiographic
      analysis included pre-operative and postoperative plain films for implant
      positioning. Functional outcomes were evaluated using the Oxford Knee Score
      (OKS), range of motion, University of California at Los Angeles (UCLA) patient
      activity-level ratings, visual analog pain scale (VAS), and the Knee Society
      Score (KSS). RESULTS: The patients had an average OKS of 21.7 pre-operatively and
      reached an average of 33.5 postoperatively (p = 0.0033). Pre-operative UCLA
      patient activity-level ratings was 3.1, compared with 4.8 postoperatively.
      Average VAS pre-operatively was 8 and postoperatively it decreased to 2.1 (p =
      0.0033). The average KSS final score pre-operatively was 56 and postoperatively
      it increased to 68.3 while the functional score pre-operatively was 47.2 compared
      to 68.1 postoperatively (p = 0.011). As a result, patello-femoral arthroplasty is
      an emerging knee resurfacing technique that is an alternative to the total knee
      arthroplasty. CONCLUSIONS: The early retrospective data for robotically-assisted
      PFA show encouraging results. Advantages of this technique include a smaller
      incision, faster rehabilitation, preservation of bone stock, and implantation
      without malalignment.

PMID- 25940606
TI  - Low incidence of early developmental dysplasia of the hip in universal
      ultrasonographic screening of newborns: analysis and evaluation of risk factors.
AB  - PURPOSE: Different timing and approaches to screening for developmental dysplasia
      of the hip (DDH) are used in the orthopaedic community. Thus ultrasonographic
      screening programs and reports based on clinical examinations produced differing
      incidence rates of DDH. Furthermore different risk factors and a change of
      incidence of DDH in the last decades were discussed. The purpose of this study
      was the evaluation of incidence and risk factors of the very early DDH in a
      modern cohort based on a universal ultrasound screening program. METHODS: We
      analysed the results of the screening program performed at our institution: 5,356
      consecutive hips of newborns were screened ultrasonographically and clinically
      according to the system published by R. Graf within the first two postnatal weeks
      [1]. A set of risk factors was analysed by univariate and multiple linear
      regression models. RESULTS: Sonographic signs of developmental dysplasia of the
      hip were found in 0.24 % of the newborns. A significant negative influence of the
      risk factors birth weight, family history of DDH and female gender on the alpha
      angle was found. Early or pre-term delivery showed a protective potential for
      DDH. CONCLUSIONS: Our data show a very low incidence of DDH in the first two
      postnatal weeks. Despite the significance of the risk factors analysed, it has to
      be considered that these factors only showed low impact on the risk of early DDH.
      In conclusion we favour universal ultrasound screening for DDH at the age of six
      to eight weeks.

PMID- 25940607
TI  - Demonstration of nonlinearity bias in the measurement of the apparent diffusion
      coefficient in multicenter trials.
AB  - PURPOSE: Characterize system-specific bias across common magnetic resonance
      imaging (MRI) platforms for quantitative diffusion measurements in multicenter
      trials. METHODS: Diffusion weighted imaging (DWI) was performed on an ice-water
      phantom along the superior-inferior (SI) and right-left (RL) orientations
      spanning +/- 150 mm. The same scanning protocol was implemented on 14 MRI systems
      at seven imaging centers. The bias was estimated as a deviation of measured from
      known apparent diffusion coefficient (ADC) along individual DWI directions. The
      relative contributions of gradient nonlinearity, shim errors, imaging gradients,
      and eddy currents were assessed independently. The observed bias errors were
      compared with numerical models. RESULTS: The measured systematic ADC errors
      scaled quadratically with offset from isocenter, and ranged between -55% (SI) and
      25% (RL). Nonlinearity bias was dependent on system design and diffusion gradient
      direction. Consistent with numerical models, minor ADC errors (+/- 5%) due to
      shim, imaging and eddy currents were mitigated by double echo DWI and image
      coregistration of individual gradient directions. CONCLUSION: The analysis
      confirms gradient nonlinearity as a major source of spatial DW bias and
      variability in off-center ADC measurements across MRI platforms, with minor
      contributions from shim, imaging gradients and eddy currents. The developed
      protocol enables empiric description of systematic bias in multicenter
      quantitative DWI studies.

PMID- 25940608
TI  - Regulation of RPTPalpha-c-Src signalling pathway by miR-218.
AB  - Receptor protein tyrosine phosphatase alpha (RPTPalpha), an activator of Src
      family kinases, is found significantly overexpressed in human cancer tissues.
      However, little is known about the regulation of RPTPalpha expression. miRNAs
      target multiple genes and play important roles in many cancer processes. Here, we
      identified a miRNA, miR-218 that binds directly to the 3'-UTR of RPTPalpha.
      Ectopic overexpression of miR-218 decreased RPTPalpha protein leading to
      decreased dephosphorylation of c-Src and decreased tumour growth in vitro and in
      vivo. A feedback loop between c-Src and miR-218 was revealed where c-Src inhibits
      transcription of SLIT2, which intronically hosts miR-218. These results show a
      novel regulatory pathway for RPTPalpha-c-Src signalling. 

PMID- 25940609
TI  - Fish Oil-Containing Emulsions: When Fat Seems to Improve Clinical Outcomes in the
      Critically Ill.

PMID- 25940610
TI  - Changes in Resting Energy Expenditure Following Orthotopic Liver Transplantation.
AB  - BACKGROUND: There is no consensus whether resting energy expenditure (REE)
      following orthotopic liver transplantation (OLT) is altered. METHODS: The
      objectives of this investigation were to describe changes in measured REE (mREE)
      using indirect calorimetry in 25 OLT patients on days 5, 10, and 15 after
      baseline (within 72 hours following OLT) and compare mREE changes with those
      calculated with 2 predicted equations for energy expenditure (pREE): the Harris
      Benedict and Schofield equations. RESULTS: Patients were 57 +/- 5.4 years of age,
      44% were male, 36% were black, and 72% had liver disease of viral etiology.
      Measured REE (at baseline and days 5, 10, and 15, per kcal/d: 1832 +/- 952, 1565
      +/- 383, 1538 +/- 345, 1578 +/- 418) and kcal per kilogram of body weight (22.7
      +/- 12.8, 18.4 +/- 4, 18.7 +/- 3.8, 21 +/- 6.5) did not change over time. In
      contrast, changes in pREE based on either the Harris-Benedict (P < .001) or
      Schofield (P = .006) equation using measured weights at each corresponding time
      point and lowest body weight during the study to estimate dry weight were
      significant. CONCLUSIONS: Wide ranges in both mREE and mREE expressed per
      kilogram of body weight at each study time point were observed in contrast to
      pREE, which declined by day 15. The observed differences in mREE over time
      suggest indirect calorimetry is indicated if available following OLT. Additional
      research is warranted to determine the most appropriate predictive equation with
      suitable stress factors to use when indirect calorimetry is not available.

PMID- 25940611
TI  - Reply: To PMID 25111587.

PMID- 25940612
TI  - Clinical experience and follow-up with large-scale single-nucleotide polymorphism
      based noninvasive prenatal aneuploidy testing.

PMID- 25940613
TI  - Special Issue of Journal of Neuroendocrinology with Peer-reviewed Articles from
      the 8th International Congress of Neuroendocrinology Held in Sydney, Australia in
      August 2014.

PMID- 25940614
TI  - Imaging the lipid bilayer of giant unilamellar vesicles using red-to-blue light
      upconversion.
AB  - Red-to-blue triplet-triplet annihilation upconversion was obtained in giant
      unilamellar vesicles. The upconverted light was homogeneously distributed across
      the membrane and could be utilized for the imaging of individual giant vesicles
      in three dimensions. These results show the great potential of TTA-UC for imaging
      applications under anoxic conditions. 

PMID- 25940615
TI  - Secondary Bacteremia: A Serious Complication of Rotavirus Gastroenteritis in
      Neonates.

PMID- 25940616
TI  - Assessment of small RNA sorting into different extracellular fractions revealed
      by high-throughput sequencing of breast cell lines.
AB  - Intercellular communication can be mediated by extracellular small regulatory
      RNAs (sRNAs). Circulating sRNAs are being intensively studied for their promising
      use as minimally invasive disease biomarkers. To date, most attention is centered
      on exosomes and microRNAs as the vectors and the secreted species, respectively.
      However, this field would benefit from an increased understanding of the plethora
      of sRNAs secreted by different cell types in different extracellular fractions.
      It is still not clear if specific sRNAs are selected for secretion, or if sRNA
      secretion is mostly passive. We sequenced the intracellular sRNA content (19-60
      nt) of breast epithelial cell lines (MCF-7 and MCF-10A) and compared it with
      extracellular fractions enriched in microvesicles, exosomes and ribonucleoprotein
      complexes. Our results are consistent with a non-selective secretion model for
      most microRNAs, although a few showed secretion patterns consistent with
      preferential secretion. On the contrary, 5' tRNA halves and 5' RNA Y4-derived
      fragments of 31-33 were greatly and significantly enriched in the extracellular
      space (even in non-mammary cell lines), where tRNA halves were detected as part
      of ~45 kDa ribonucleoprotein complexes. Overall, we show that different sRNA
      families have characteristic secretion patterns and open the question of the role
      of these sRNAs in the extracellular space. 

PMID- 25940617
TI  - Shape-selective recognition of DNA abasic sites by metallohelices: inhibition of
      human AP endonuclease 1.
AB  - Loss of a base in DNA leading to creation of an abasic (AP) site leaving a
      deoxyribose residue in the strand, is a frequent lesion that may occur
      spontaneously or under the action of various physical and chemical agents.
      Progress in the understanding of the chemistry and enzymology of abasic DNA
      largely relies upon the study of AP sites in synthetic duplexes. We report here
      on interactions of diastereomerically pure metallo-helical 'flexicate' complexes,
      bimetallic triple-stranded ferro-helicates [Fe2(NN-NN)3](4+) incorporating the
      common NN-NN bis(bidentate) helicand, with short DNA duplexes containing AP sites
      in different sequence contexts. The results show that the flexicates bind to AP
      sites in DNA duplexes in a shape-selective manner. They preferentially bind to AP
      sites flanked by purines on both sides and their binding is enhanced when a
      pyrimidine is placed in opposite orientation to the lesion. Notably, the Lambda
      enantiomer binds to all tested AP sites with higher affinity than the Delta
      enantiomer. In addition, the binding of the flexicates to AP sites inhibits the
      activity of human AP endonuclease 1, which is as a valid anticancer drug target.
      Hence, this finding indicates the potential of utilizing well-defined metallo
      helical complexes for cancer chemotherapy. 

PMID- 25940619
TI  - RNAPattMatch: a web server for RNA sequence/structure motif detection based on
      pattern matching with flexible gaps.
AB  - Searching for RNA sequence-structure patterns is becoming an essential tool for
      RNA practitioners. Novel discoveries of regulatory non-coding RNAs in targeted
      organisms and the motivation to find them across a wide range of organisms have
      prompted the use of computational RNA pattern matching as an enhancement to
      sequence similarity. State-of-the-art programs differ by the flexibility of
      patterns allowed as queries and by their simplicity of use. In particular-no
      existing method is available as a user-friendly web server. A general program
      that searches for RNA sequence-structure patterns is RNA Structator. However, it
      is not available as a web server and does not provide the option to allow
      flexible gap pattern representation with an upper bound of the gap length being
      specified at any position in the sequence. Here, we introduce RNAPattMatch, a web
      based application that is user friendly and makes sequence/structure RNA queries
      accessible to practitioners of various background and proficiency. It also
      extends RNA Structator and allows a more flexible variable gaps representation,
      in addition to analysis of results using energy minimization methods.
      RNAPattMatch service is available at http://www.cs.bgu.ac.il/rnapattmatch. A
      standalone version of the search tool is also available to download at the site. 

PMID- 25940618
TI  - Arginine methylation of DRBD18 differentially impacts its opposing effects on the
      trypanosome transcriptome.
AB  - Arginine methylation is a posttranslational modification that impacts wide
      ranging cellular functions, including transcription, mRNA splicing and
      translation. RNA binding proteins (RBPs) represent one of the largest classes of
      arginine methylated proteins in both mammals and the early diverging parasitic
      protozoan, Trypanosoma brucei. Here, we report the effects of arginine
      methylation on the functions of the essential and previously uncharacterized T.
      brucei RBP, DRBD18. RNAseq analysis shows that DRBD18 depletion causes extensive
      rearrangement of the T. brucei transcriptome, with increases and decreases in
      hundreds of mRNAs. DRBD18 contains three methylated arginines, and we used
      complementation of DRBD18 knockdown cells with methylmimic or hypomethylated
      DRBD18 to assess the functions of these methylmarks. Methylmimic and
      hypomethylated DRBD18 associate with different ribonucleoprotein complexes. These
      altered macromolecular interactions translate into differential impacts on the T.
      brucei transcriptome. Methylmimic DRBD18 preferentially stabilizes target RNAs,
      while hypomethylated DRBD18 is more efficient at destabilizing RNA. The protein
      arginine methyltransferase, TbPRMT1, interacts with DRBD18 and knockdown of
      TbPRMT1 recapitulates the effects of hypomethylated DRBD18 on mRNA levels.
      Together, these data support a model in which arginine methylation acts as a
      switch that regulates T. brucei gene expression. 

PMID- 25940620
TI  - Structural insights into catalysis and dimerization enhanced exonuclease activity
      of RNase J.
AB  - RNase J is a conserved ribonuclease that belongs to the beta-CASP family of
      nucleases. It possesses both endo- and exo-ribonuclease activities, which play a
      key role in pre-rRNA maturation and mRNA decay. Here we report high-resolution
      crystal structures of Deinococcus radiodurans RNase J complexed with RNA or
      uridine 5'-monophosphate in the presence of manganese ions. Biochemical and
      structural studies revealed that RNase J uses zinc ions for two-metal-ion
      catalysis. One residue conserved among RNase J orthologues (motif B) forms
      specific electrostatic interactions with the scissile phosphate of the RNA that
      is critical for the catalysis and product stabilization. The additional manganese
      ion, which is coordinated by conserved residues at the dimer interface, is
      critical for RNase J dimerization and exonuclease activity. The structures may
      also shed light on the mechanism of RNase J exo- and endonucleolytic activity
      switch. 

PMID- 25940621
TI  - Mechanistic insights into temperature-dependent regulation of the simple
      cyanobacterial hsp17 RNA thermometer at base-pair resolution.
AB  - The cyanobacterial hsp17 ribonucleicacid thermometer (RNAT) is one of the
      smallest naturally occurring RNAT. It forms a single hairpin with an internal 1*3
      bulge separating the start codon in stem I from the ribosome binding site (RBS)
      in stem II. We investigated the temperature-dependent regulation of hsp17 by
      mapping individual base-pair stabilities from solvent exchange nuclear magnetic
      resonance (NMR) spectroscopy. The wild-type RNAT was found to be stabilized by
      two critical CG base pairs (C14-G27 and C13-G28). Replacing the internal 1*3
      bulge by a stable CG base pair in hsp17(rep) significantly increased the global
      stability and unfolding cooperativity as evidenced by circular dichroism
      spectroscopy. From the NMR analysis, remote stabilization and non-nearest
      neighbour effects exist at the base-pair level, in particular for nucleotide G28
      (five nucleotides apart from the side of mutation). Individual base-pair
      stabilities are coupled to the stability of the entire thermometer within both
      the natural and the stabilized RNATs by enthalpy-entropy compensation presumably
      mediated by the hydration shell. At the melting point the Gibbs energies of the
      individual nucleobases are equalized suggesting a consecutive zipper-type
      unfolding mechanism of the RBS leading to a dimmer-like function of hsp17 and
      switch-like regulation behaviour of hsp17(rep). The data show how minor changes
      in the nucleotide sequence not only offset the melting temperature but also alter
      the mode of temperature sensing. The cyanobacterial thermosensor demonstrates the
      remarkable adjustment of natural RNATs to execute precise temperature control. 

PMID- 25940622
TI  - The SOX9 upstream region prone to chromosomal aberrations causing campomelic
      dysplasia contains multiple cartilage enhancers.
AB  - Two decades after the discovery that heterozygous mutations within and around
      SOX9 cause campomelic dysplasia, a generalized skeleton malformation syndrome, it
      is well established that SOX9 is a master transcription factor in chondrocytes.
      In contrast, the mechanisms whereby translocations in the --350/-50-kb region 5'
      of SOX9 cause severe disease and whereby SOX9 expression is specified in
      chondrocytes remain scarcely known. We here screen this upstream region and
      uncover multiple enhancers that activate Sox9-promoter transgenes in the SOX9
      expression domain. Three of them are primarily active in chondrocytes. E250
      (located at -250 kb) confines its activity to condensed prechondrocytes, E195
      mainly targets proliferating chondrocytes, and E84 is potent in all
      differentiated chondrocytes. E84 and E195 synergize with E70, previously shown to
      be active in most Sox9-expressing somatic tissues, including cartilage. While
      SOX9 protein powerfully activates E70, it does not control E250. It requires its
      SOX5/SOX6 chondrogenic partners to robustly activate E195 and additional factors
      to activate E84. Altogether, these results indicate that SOX9 expression in
      chondrocytes relies on widely spread transcriptional modules whose synergistic
      and overlapping activities are driven by SOX9, SOX5/SOX6 and other factors. They
      help elucidate mechanisms underlying campomelic dysplasia and will likely help
      uncover other disease mechanisms. 

PMID- 25940623
TI  - MapMyFlu: visualizing spatio-temporal relationships between related influenza
      sequences.
AB  - Understanding the molecular dynamics of viral spreading is crucial for
      anticipating the epidemiological implications of disease outbreaks. In the case
      of influenza, reassortments or point mutations affect the adaption to new hosts
      or resistance to anti-viral drugs and can determine whether a new strain will
      result in a pandemic infection or a less severe progression. To this end, tools
      integrating molecular information with epidemiological parameters are important
      to understand how molecular characteristics reflect in the infection dynamics. We
      present a new web tool, MapMyFlu, which allows to spatially and temporally
      display influenza viruses related to a query sequence on a Google Map based on
      BLAST results against the NCBI Influenza Database. Temporal and geographical
      trends appear clearly and may help in reconstructing the evolutionary history of
      a particular sequence. The tool is accessible through a web server, hence without
      the need for local installation. The website has an intuitive design and provides
      an easy-to-use service, and is available at http://mapmyflu.ipmb.uni
      heidelberg.de. 

PMID- 25940624
TI  - Prediction of nucleic acid binding probability in proteins: a neighboring residue
      network based score.
AB  - We describe a general binding score for predicting the nucleic acid binding
      probability in proteins. The score is directly derived from physicochemical and
      evolutionary features and integrates a residue neighboring network approach. Our
      process achieves stable and high accuracies on both DNA- and RNA-binding proteins
      and illustrates how the main driving forces for nucleic acid binding are common.
      Because of the effective integration of the synergetic effects of the network of
      neighboring residues and the fact that the prediction yields a hierarchical
      scoring on the protein surface, energy funnels for nucleic acid binding appear on
      protein surfaces, pointing to the dynamic process occurring in the binding of
      nucleic acids to proteins. 

PMID- 25940626
TI  - The telomerase essential N-terminal domain promotes DNA synthesis by stabilizing
      short RNA-DNA hybrids.
AB  - Telomerase is an enzyme that adds repetitive DNA sequences to the ends of
      chromosomes and consists of two main subunits: the telomerase reverse
      transcriptase (TERT) protein and an associated telomerase RNA (TER). The
      telomerase essential N-terminal (TEN) domain is a conserved region of TERT
      proposed to mediate DNA substrate interactions. Here, we have employed single
      molecule telomerase binding assays to investigate the function of the TEN domain.
      Our results reveal telomeric DNA substrates bound to telomerase exhibit a dynamic
      equilibrium between two states: a docked conformation and an alternative
      conformation. The relative stabilities of the docked and alternative states
      correlate with the number of basepairs that can be formed between the DNA
      substrate and the RNA template, with more basepairing favoring the docked state.
      The docked state is further buttressed by the TEN domain and mutations within the
      TEN domain substantially alter the DNA substrate structural equilibrium. We
      propose a model in which the TEN domain stabilizes short RNA-DNA duplexes in the
      active site of the enzyme, promoting the docked state to augment telomerase
      processivity. 

PMID- 25940625
TI  - Accurate identification of centromere locations in yeast genomes using Hi-C.
AB  - Centromeres are essential for proper chromosome segregation. Despite extensive
      research, centromere locations in yeast genomes remain difficult to infer, and in
      most species they are still unknown. Recently, the chromatin conformation capture
      assay, Hi-C, has been re-purposed for diverse applications, including de novo
      genome assembly, deconvolution of metagenomic samples and inference of centromere
      locations. We describe a method, Centurion, that jointly infers the locations of
      all centromeres in a single genome from Hi-C data by exploiting the centromeres'
      tendency to cluster in three-dimensional space. We first demonstrate the accuracy
      of Centurion in identifying known centromere locations from high coverage Hi-C
      data of budding yeast and a human malaria parasite. We then use Centurion to
      infer centromere locations in 14 yeast species. Across all microbes that we
      consider, Centurion predicts 89% of centromeres within 5 kb of their known
      locations. We also demonstrate the robustness of the approach in datasets with
      low sequencing depth. Finally, we predict centromere coordinates for six yeast
      species that currently lack centromere annotations. These results show that
      Centurion can be used for centromere identification for diverse species of yeast
      and possibly other microorganisms. 

PMID- 25940629
TI  - NFFinder: an online bioinformatics tool for searching similar transcriptomics
      experiments in the context of drug repositioning.
AB  - Drug repositioning, using known drugs for treating conditions different from
      those the drug was originally designed to treat, is an important drug discovery
      tool that allows for a faster and cheaper development process by using drugs that
      are already approved or in an advanced trial stage for another purpose. This is
      especially relevant for orphan diseases because they affect too few people to
      make drug research de novo economically viable. In this paper we present
      NFFinder, a bioinformatics tool for identifying potential useful drugs in the
      context of orphan diseases. NFFinder uses transcriptomic data to find
      relationships between drugs, diseases and a phenotype of interest, as well as
      identifying experts having published on that domain. The application shows in a
      dashboard a series of graphics and tables designed to help researchers formulate
      repositioning hypotheses and identify potential biological relationships between
      drugs and diseases. NFFinder is freely available at http://nffinder.cnb.csic.es. 

PMID- 25940627
TI  - Role of intragenic binding of cAMP responsive protein (CRP) in regulation of the
      succinate dehydrogenase genes Rv0249c-Rv0247c in TB complex mycobacteria.
AB  - Bacterial pathogens adapt to changing environments within their hosts, and the
      signaling molecule adenosine 3', 5'-cyclic monophosphate (cAMP) facilitates this
      process. In this study, we characterized in vivo DNA binding and gene regulation
      by the cAMP-responsive protein CRP in M. bovis BCG as a model for tuberculosis
      (TB)-complex bacteria. Chromatin immunoprecipitation followed by deep-sequencing
      (ChIP-seq) showed that CRP associates with ~900 DNA binding regions, most of
      which occur within genes. The most highly enriched binding region was upstream of
      a putative copper transporter gene (ctpB), and crp-deleted bacteria showed
      increased sensitivity to copper toxicity. Detailed mutational analysis of four
      CRP binding sites upstream of the virulence-associated Rv0249c-Rv0247c succinate
      dehydrogenase genes demonstrated that CRP directly regulates Rv0249c-Rv0247c
      expression from two promoters, one of which requires sequences intragenic to
      Rv0250c for maximum expression. The high percentage of intragenic CRP binding
      sites and our demonstration that these intragenic DNA sequences significantly
      contribute to biologically relevant gene expression greatly expand the genome
      space that must be considered for gene regulatory analyses in mycobacteria. These
      findings also have practical implications for an important bacterial pathogen in
      which identification of mutations that affect expression of drug target-related
      genes is widely used for rapid drug resistance screening. 

PMID- 25940628
TI  - Generation of functionally distinct isoforms of PTBP3 by alternative splicing and
      translation initiation.
AB  - Polypyrimidine tract binding protein (PTBP1) is a widely expressed RNA binding
      protein that acts as a regulator of alternative splicing and of cytoplasmic mRNA
      functions. Vertebrates contain two closely-related paralogs with >75% amino acid
      sequence identity. Early replacement of PTBP1 by PTBP2 during neuronal
      differentiation causes a concerted set of splicing changes. By comparison, very
      little is known about the molecular functions or physiological roles of PTBP3,
      although its expression and conservation throughout the vertebrates suggest a
      role in haematopoietic cells. To begin to understand its functions we have
      characterized the mRNA and protein isoform repertoire of PTBP3. Combinatorial
      alternative splicing events at the 5' end of the gene allow for the generation of
      eight mRNA and three major protein isoforms. Individual mRNAs generate up to
      three protein isoforms via alternative translation initiation by re-initiation
      and leaky scanning using downstream AUG codons. The N-terminally truncated PTBP3
      isoforms lack nuclear localization signals and/or most of the RRM1 domain and
      vary in their RNA binding properties and nuclear/cytoplasmic distribution,
      suggesting that PTBP3 may have major post-transcriptional cytoplasmic roles. Our
      findings set the stage for understanding the non-redundant physiological roles of
      PTBP3. 

PMID- 25940630
TI  - Galahad: a web server for drug effect analysis from gene expression.
AB  - Galahad (https://galahad.esat.kuleuven.be) is a web-based application for
      analysis of drug effects. It provides an intuitive interface to be used by
      anybody interested in leveraging microarray data to gain insights into the
      pharmacological effects of a drug, mainly identification of candidate targets,
      elucidation of mode of action and understanding of off-target effects. The core
      of Galahad is a network-based analysis method of gene expression. As an input,
      Galahad takes raw Affymetrix human microarray data from treatment versus control
      experiments and provides quality control and data exploration tools, as well as
      computation of differential expression. Alternatively, differential expression
      values can be uploaded directly. Using these differential expression values, drug
      target prioritization and both pathway and disease enrichment can be calculated
      and visualized. Drug target prioritization is based on the integration of the
      gene expression data with a functional protein association network. The web site
      is free and open to all and there is no login requirement. 

PMID- 25940632
TI  - FNTM: a server for predicting functional networks of tissues in mouse.
AB  - Functional Networks of Tissues in Mouse (FNTM) provides biomedical researchers
      with tissue-specific predictions of functional relationships between proteins in
      the most widely used model organism for human disease, the laboratory mouse.
      Users can explore FNTM-predicted functional relationships for their tissues and
      genes of interest or examine gene function and interaction predictions across
      multiple tissues, all through an interactive, multi-tissue network browser. FNTM
      makes predictions based on integration of a variety of functional genomic data,
      including over 13 000 gene expression experiments, and prior knowledge of gene
      function. FNTM is an ideal starting point for clinical and translational
      researchers considering a mouse model for their disease of interest, researchers
      already working with mouse models who are interested in discovering new genes
      related to their pathways or phenotypes of interest, and biologists working with
      other organisms to explore the functional relationships of their genes of
      interest in specific mouse tissue contexts. FNTM predicts tissue-specific
      functional relationships in 200 tissues, does not require any registration or
      installation and is freely available for use at http://fntm.princeton.edu. 

PMID- 25940633
TI  - Inefficiency in macromolecular transport of SCS-based microcapsules affects
      viability of primary human mesenchymal stem cells but not of immortalized cells.
AB  - Microcapsules made of sodium cellulose sulphate (SCS) and poly-diallyl-dimethyl
      ammonium chloride (pDADMAC) have been employed to encapsulate a wide range of
      established cell lines for several applications. However, little is known about
      the encapsulation of primary cells including human mesenchymal stem cells
      (hMSCs). Human MSCs are of interest in regenerative medicine applications due to
      pro-angiogenic, anti-inflammatory and immunomodulatory properties, which result
      from paracrine effects of this cell type. In the present work we have
      encapsulated primary hMSCs and hMSC-TERT immortalized cells and compared their
      behavior and in vitro angiogenic potential. We found that, although both cell
      types were able to secret angiogenic factors such as VEGF, there was a marked
      reduction of primary hMSC viability compared to hMSC-TERT cells when cultured in
      these microcapsules. Moreover, this applied to other primary cell cultures such
      as primary human fibroblasts but not to other cell lines such as human embryonic
      kidney 293 (HEK293) cells. We found that the microcapsule membrane had a
      molecular weight cut-off below a critical size, which caused impairment in the
      diffusion of essential nutrients and had a more detrimental effect on the
      viability of primary cell cultures compared to cell lines and immortalized cells.

PMID- 25940634
TI  - Top tips for social media use in sports and exercise medicine: doing the right
      thing in the digital age.

PMID- 25940631
TI  - Loop flexibility in human telomeric quadruplex small-molecule complexes.
AB  - Quadruplex nucleic acids can be formed at the ends of eukaryotic chromosomes.
      Their formation and stabilisation by appropriate small molecules can be used as a
      means of inhibiting the telomere maintenance functions of telomerase in human
      cancer cells. The crystal structures have been determined for a number of
      complexes between these small molecules and human telomeric DNA and RNA
      quadruplexes. The detailed structural characteristics of these complexes have
      been surveyed here and the variations in conformation for the TTA and UUA loops
      have been explored. Loop conformations have been classified in terms of a number
      of discrete types and their distribution among the crystal structures. Sugar
      conformation and backbone angles have also been examined and trends highlighted.
      One particular loop class has been found to be most prevalent. Implications for
      in particular, rational drug design, are discussed. 

PMID- 25940635
TI  - Muscle metabolism changes with age and maturation: How do they relate to youth
      sport performance?
AB  - AIM: To provide an evidence-based review of muscle metabolism changes with sex-,
      age- and maturation with reference to the development of youth sport performance.
      METHODS: A narrative review of data from both invasive and non-invasive studies,
      from 1970 to 2015, founded on personal databases supported with computer searches
      of PubMed and Google Scholar. RESULTS: Youth sport performance is underpinned by
      sex-, age- and maturation-related changes in muscle metabolism. Investigations of
      muscle size, structure and metabolism; substrate utilisation; pulmonary oxygen
      uptake kinetics; muscle phosphocreatine kinetics; peak anaerobic and aerobic
      performance; and fatigue resistance; determined using a range of conventional and
      emerging techniques present a consistent picture. Age-related changes have been
      consistently documented but specific and independent maturation-related effects
      on muscle metabolism during exercise have proved elusive to establish. Children
      are better equipped for exercise supported primarily by oxidative metabolism than
      by anaerobic metabolism. Sexual dimorphism is apparent in several physiological
      variables underpinning youth sport performance. As young people mature there is a
      progressive but asynchronous transition into an adult metabolic profile.
      CONCLUSIONS: The application of recent developments in technology to the
      laboratory study of the exercising child and adolescent has both supplemented
      existing knowledge and provided novel insights into developmental exercise
      physiology. A sound foundation of laboratory-based knowledge has been established
      but the lack of rigorously designed child-specific and sport-specific testing
      environments has clouded the interpretation of the data in real life situations.
      The primary challenge remains the translation of laboratory research into the
      optimisation of youth sports participation and performance.

PMID- 25940636
TI  - Rationale, secondary outcome scores and 1-year follow-up of a randomised trial of
      platelet-rich plasma injections in acute hamstring muscle injury: the Dutch
      Hamstring Injection Therapy study.
AB  - BACKGROUND: Platelet-rich plasma (PRP) injections are an experimental treatment
      for acute muscle injuries. We examined whether PRP injections would accelerate
      return to play after hamstring injury. The methods and the primary outcome
      measure were published in the New England Journal of Medicine (NEJM) as 'Platelet
      rich plasma injections in acute muscle injury' (2014). This article shares
      information not available in the NEJM letter or online supplement, especially the
      rationale behind the study and the secondary outcome measures including 1 year re
      injury data. METHODS: We performed a multicentre, randomised, double-blind,
      placebo-controlled trial in 80 competitive and recreational athletes with acute
      hamstring muscle injuries. Details can be found in the NEJM
      (http://www.nejm.org/doi/full/10.1056/NEJMc1402340). The primary outcome measure
      was the time needed to return to play during 6 months of follow-up. Not
      previously reported secondary outcome scores included re-injury at 1 year,
      alteration in clinical and MRI parameters, subjective patient satisfaction and
      the hamstring outcome score. RESULTS: In the earlier NEJM publication, we
      reported that PRP did not accelerate return to play; nor did we find a difference
      in the 2-month re-injury rate. We report no significant between-group difference
      in the 1-year re-injury rate (HR=0.89; 95% CI, 0.38 to 2.13; p=0.80) or any other
      secondary outcome measure. CONCLUSIONS: At 1-year postinjection, we found no
      benefit of intramuscular PRP compared with placebo injections in patients with
      acute hamstring injuries in the time to return to play, re-injury rate and
      alterations of subjective, clinical or MRI measures.

PMID- 25940637
TI  - Assessment of Anatomic Risk During Syndesmotic Stabilization With the Suture
      Button Technique.
AB  - The suture button technique represents an accepted method of fixation for acute
      or chronic injury to the tibiofibular syndesmosis. The objective of the present
      investigation was to assess the anatomic risk to the superficial medial
      neurovascular structure with insertion of a syndesmotic suture button and to
      measure the distance of the button to the greater saphenous vein during a
      standardized insertion. A syndesmotic suture button was inserted with a
      standardized technique in 20 fresh frozen cadaveric limbs. Of 20 suture buttons,
      14 (70.0%) were inserted posterior to the greater saphenous vein, 2 (10.0%) were
      inserted anterior to the greater saphenous vein, and 4 (20.0%) were inserted
      directly onto the greater saphenous vein. A total of 11 suture buttons (55.0%)
      were inserted with some entrapment of a medial neurovascular structure. The
      absolute mean +/- standard deviation distance of the suture button to the greater
      saphenous vein was 4.88 +/- 4.44 mm. The results of the present investigation
      have indicated that a risk of entrapment of superficial medial neurovascular
      structures exists with insertion of a suture button for syndesmotic fixation and
      that a medial incision should be used to ensure that structures are not
      entrapped. 

PMID- 25940638
TI  - A fluorescence-based array screen for transglutaminase substrates.
AB  - Transglutaminases (EC 2.3.2.13) form an enzyme family that catalyzes the
      formation of isopeptide bonds between the gamma-carboxamide group of glutamine
      and the epsilon-amine group of lysine residues of peptides and proteins. Other
      primary amines can be accepted in place of lysine. Because of their important
      physiological and pathophysiological functions, transglutaminases have been
      studied for 60 years. However, the substrate preferences of this enzyme class
      remain largely elusive. In this study, we used focused combinatorial libraries of
      400 peptides to investigate the influence of the amino acids adjacent to the
      glutamine and lysine residues on the catalysis of isopeptide bond formation by
      microbial transglutaminase. Using the peptide microarray technology we found a
      strong positive influence of hydrophobic and basic amino acids, especially
      arginine, tyrosine, and leucine. Several tripeptide substrates were synthesized,
      and enzymatic kinetic parameters were determined both by microarray analysis and
      in solution.

PMID- 25940639
TI  - Outer membrane proteomics of kanamycin-resistant Escherichia coli identified MipA
      as a novel antibiotic resistance-related protein.
AB  - Antibiotic-resistant bacteria are a great threat to human health and food safety
      and there is an urgent need to understand the mechanisms of resistance for
      combating these bacteria. In the current study, comparative proteomic
      methodologies were applied to identify Escherichia coli K-12 outer membrane (OM)
      proteins related to kanamycin resistance. Mass spectrometry and western blotting
      results revealed that OM proteins TolC, Tsx and OstA were up-regulated, whereas
      MipA, OmpA, FadL and OmpW were down-regulated in kanamycin-resistant E. coli K-12
      strain. Genetic deletion of tolC (DeltatolC-Km) led to a 2-fold decrease in the
      minimum inhibitory concentration (MIC) of kanamycin and deletion of mipA
      (DeltamipA-Km) resulted in a 4-fold increase in the MIC of kanamycin. Changes in
      the MICs for genetically modified strains could be completely recovered by gene
      complementation. Compared with the wild-type strain, the survival capability of
      DeltaompA-Km was significantly increased and that of Deltatsx-Km was
      significantly decreased. We further evaluated the role and expression of MipA in
      response to four other antibiotics including nalidixic acid, streptomycin,
      chloramphenicol and aureomycin, which suggested that MipA was a novel OM protein
      related to antibiotic resistance. 

PMID- 25940640
TI  - Disutility in Patients with Hidradenitis Suppurativa: A Cross-sectional Study
      Using EuroQoL-5D.
AB  - Disutility reflects the disability caused by a disease. The EuroQoL-5D (EQ-5D)
      questionnaire is a measure of health-related overall utility. The questionnaire
      has only been applied previously to a small number of patients with hidradenitis.
      In this study a survey of 421 patients with hidradenitis suppurativa was
      conducted using the EQ-5D questionnaire. Questions regarding pain, malodour and
      pruritus were included to determine quantitatively whether these factors are
      associated with low EQ-5D index and visual analogue scale (VAS) scores. The index
      and VAS scores obtained were compared with reference values for the general
      population in Denmark. A significantly decreased utility in patients with
      hidradenitis suppurativa was found for all age group levels, except for 65-74
      year-olds. The total index score in the cohort was 0.705 (population mean 0.887)
      and the VAS was 62.25 (population mean 82.6). Multivariate analysis found
      significant associations between loss of utility and pain, malodour and pruritus
      (p < 0.0001). Patients with hidradenitis suppurativa had a significantly
      decreased EQ-5D compared with the background population. Malodour and pruritus
      were found to be associated with low index values, and pain and malodour with low
      VAS. Patient-reported pain and discomfort had the most negative overall effect on
      mean index scores. 

PMID- 25940641
TI  - Reciprocal obligations for prevention of occupationally acquired tuberculosis
      among healthcare workers.
AB  - As I began my work on occupationally acquired tuberculosis (TB), I was perturbed
      by a series of media reports on TB among healthcare workers (HCWs) in India. This
      included a report on the death of a resident doctor who was suffering from
      multidrug-resistant (MDR) TB. The risk of occupationally acquired TB is well
      documented. A few studies have reported an increased risk of TB among HCWs in
      developing countries, including India. 

PMID- 25940642
TI  - Maternal overweight and obesity are associated with increased risk of type 1
      diabetes in offspring of parents without diabetes regardless of ethnicity.
AB  - AIMS/HYPOTHESIS: The incidence of type 1 diabetes in children is increasing in
      Sweden, as is the prevalence of maternal overweight/obesity. Therefore, the aim
      of this study was to investigate if maternal overweight/obesity increases the
      risk of type 1 diabetes in offspring of parents with and without diabetes, and of
      different ethnicities. METHODS: The study cohort comprised 1,263,358 children,
      born in Sweden between 1992 and 2004. Children were followed from birth until
      diagnosis of type 1 diabetes, emigration, death or end of follow-up in 2009,
      whichever occurred first. First trimester maternal BMI was calculated (kg/m(2)).
      Poisson regression was used to calculate incidence rate ratios (IRRs) with 95% CI
      for type 1 diabetes in the offspring. RESULTS: The risk of type 1 diabetes was
      increased in offspring of parents with any type of diabetes regardless of
      parental ethnicity. High first trimester maternal BMI was associated with
      increased risk of type 1 diabetes only in offspring of parents without diabetes
      (IRR 1.33 [95% CI 1.20, 1.48]). CONCLUSIONS/INTERPRETATION: Increasing incidence
      of type 1 diabetes in children with non-diabetic parents may partly be explained
      by increasing prevalence of maternal overweight/obesity.

PMID- 25940644
TI  - The usefulness of combined axial and coronal computed tomography for the
      evaluation of metastatic supraclavicular lymph nodes.
AB  - The purpose is to assess the value of adding coronal images for the
      identification of metastatic supraclavicular lymph nodes (LNs). Two radiologists
      reviewed axial images and combined axial and coronal images using thoracic
      computed tomography (CT) of 386 patients whose maximum standardized uptake value
      measured in a supraclavicular LN was >=2.0 on a positron emission tomography. We
      compared sensitivity and agreement between readers before and after the addition
      of coronal images. For combined images, agreement was almost perfect
      (kappa=0.982), and sensitivity was significantly higher (90.4%, P<.001).
      Interpreting both axial and coronal images improves the diagnostic accuracy for
      supraclavicular metastasis. 

PMID- 25940643
TI  - Higher glucose, insulin and insulin resistance (HOMA-IR) in childhood predict
      adverse cardiovascular risk in early adulthood: the Pune Children's Study.
AB  - AIMS/HYPOTHESIS: The Pune Children's Study aimed to test whether glucose and
      insulin measurements in childhood predict cardiovascular risk factors in young
      adulthood. METHODS: We followed up 357 participants (75% follow-up) at 21 years
      of age who had undergone detailed measurements at 8 years of age (glucose,
      insulin, HOMA-IR and other indices). Oral glucose tolerance, anthropometry,
      plasma lipids, BP, carotid intima-media thickness (IMT) and arterial pulse wave
      velocity (PWV) were measured at 21 years. RESULTS: Higher fasting glucose,
      insulin and HOMA-IR at 8 years predicted higher glucose, insulin, HOMA-IR, BP,
      lipids and IMT at 21 years. A 1 SD change in 8 year variables was associated with
      a 0.10-0.27 SD change at 21 years independently of obesity/adiposity at 8 years
      of age. A greater rise in glucose-insulin variables between 8 and 21 years was
      associated with higher cardiovascular risk factors, including PWV. Participants
      whose HOMA-IR measurement remained in the highest quartile (n = 31) had a more
      adverse cardiovascular risk profile compared with those whose HOMA-IR measurement
      remained in the lowest quartile (n = 28). CONCLUSIONS/INTERPRETATION: Prepubertal
      glucose-insulin metabolism is associated with adult cardiovascular risk and
      markers of atherosclerosis. Our results support interventions to improve glucose
      insulin metabolism in childhood to reduce cardiovascular risk in later life.

PMID- 25940645
TI  - Endovenous laser ablation is an effective treatment for great saphenous vein
      incompetence in teenagers.
AB  - OBJECTIVES: The current knowledge of chronic venous disease in teenagers and its
      treatment is very limited. The aim of the study is to present our experience and
      the available literature data on the treatment of varicose veins in teenagers
      with endovenous laser ablation of the great saphenous vein. METHODS: Five
      patients, aged 15-17 years, were qualified for surgery, based on typical signs
      and symptoms of chronic venous disease. Minimally invasive treatment with
      endovenous laser ablation of the great saphenous vein was applied. RESULTS: The
      technical success of surgery was achieved in all patients. Over a 2-year follow
      up we did not observe any case of recanalisation of the great saphenous vein,
      recurrence of varicose veins, or serious complications, such as deep vein
      thrombosis or pulmonary embolism. One patient presented with resolving of post
      operative bruising, and two cases of local numbness were transient. CONCLUSIONS:
      Endovenous laser ablation of the great saphenous vein in the treatment of chronic
      venous disease in teenagers is effective and safe. The method provides excellent
      cosmetic effects, very short recovery time and high levels of patient
      satisfaction.

PMID- 25940646
TI  - Fluorinated hydroxypiperidines as selective beta-glucosidase inhibitors.
AB  - A new series of fluoroallylamines derived from hydroxypiperidines was prepared
      and evaluated against various glycosidases. The short synthesis of target
      molecules involved the modified Julia reaction between aldehydes and
      functionalized fluoroaminosulfones. Biological studies revealed good and
      selective beta-glucosidase inhibition in the micromolar range for two compounds,
      while the non-fluorinated analogue of the most active compound was selective
      towards alpha-glucosidase. 

PMID- 25940647
TI  - An oil-soluble extract of Rubus idaeus cells enhances hydration and water
      homeostasis in skin cells.
AB  - OBJECTIVE: Raspberry plants, belonging to the species of Rubus idaeus, are known
      for their excellent therapeutic properties as they are particularly rich in
      compounds with strong antioxidant activity, which promote health and well-being
      of human cells. Besides their high content of phenolic compounds, Rubus plants
      are rich in oil-soluble compounds, which are also primary components of the
      hydrolipidic film barrier of the skin. As plant cell cultures represented a
      valuable system to produce interesting compounds and ingredients for cosmetic
      applications, we developed liquid suspension cultures from Rubus idaeus leaves
      and used them to obtain an active ingredient aimed at improving hydration and
      moisturization capacity in the skin. METHODS: Rubus idaeus cells, grown in the
      laboratory under sterile and controlled conditions as liquid suspension cultures,
      were processed to obtain an oil-soluble (liposoluble) extract, containing
      phenolic compounds and a wide range of fatty acids. The extract was tested on
      cultured keratinocytes and fibroblasts and then on the skin in vivo, to assess
      its cosmetic activities. RESULTS: When tested on skin cell cultures, the extract
      induced the genes responsible for skin hydration, such as aquaporin 3, filaggrin,
      involucrin and hyaluronic acid synthase, and stimulated the expression and the
      activity of the enzyme glucocerebrosidase, involved in ceramide production.
      Moreover, the liposoluble extract increased the synthesis of the extracellular
      matrix components in cultured fibroblasts and showed a remarkable skin-hydrating
      capacity when tested on human skin in vivo. CONCLUSIONS: Thanks to these
      activities, the Rubus idaeus liposoluble extract has several potential
      applications in skin care cosmetics: it can be used as hydrating and moisturizing
      ingredient in face and body lotions, and as anti-ageing product in face creams
      specifically designed to fight wrinkle formation.

PMID- 25940648
TI  - A pilot study to promote walking among obese and overweight individuals: walking
      buses for adults.

PMID- 25940649
TI  - 1815 and all that.

PMID- 25940650
TI  - Blood Urea Nitrogen/Creatinine Ratio and Response to Tolvaptan in Patients with
      Decompensated Heart Failure: A Retrospective Analysis.
AB  - INTRODUCTION: Arginine vasopressin-stimulated reabsorption of urea occurs in the
      collecting duct via increased expression of the urea transporter. OBJECTIVE: The
      aim of this study was to evaluate whether the blood urea nitrogen/creatinine
      (BUN/Cr) ratio is useful for predicting tolvaptan response in patients with
      decompensated heart failure (HF). METHODS: Among 71 consecutive patients with HF
      who received oral tolvaptan between 2010 and 2014, we retrospectively studied 33
      patients with decompensated HF without any mechanical circulatory assistance or
      inotropic support who had already been treated with loop diuretics. A responder
      to tolvaptan was defined as an individual who experienced a >=30 % increase in
      their respective 24-h urine volume. RESULTS: Among the 33 patients, 21 met the
      criteria of a responder. The area under the receiver operating characteristic
      curves of BUN/Cr and BUN were 0.790 and 0.714, respectively, and the respective
      cut-off values for responders to tolvaptan were 23.8 and 49.0. BUN/Cr and BUN
      retained their significant relationships with the responder status (odds ratio
      for BUN/Cr >23.8: 20.9; 95 % confidence interval [CI] 2.7-531.1; p = 0.002; odds
      ratio for BUN >=49: 7.7; 95 % CI 1.4-65.8; p = 0.02). CONCLUSION: Our results
      suggest that high BUN/Cr may be a predictor of response to tolvaptan in
      decompensated HF patients. A prospective study with a large sample size is
      required to confirm this preliminary finding.

PMID- 25940651
TI  - Bleeding Risk, Management and Outcome in Patients Receiving Non-VKA Oral
      Anticoagulants (NOACs).
AB  - Modern direct-acting anticoagulants are rapidly replacing vitamin K antagonists
      (VKA) in the management of millions of patients worldwide who require
      anticoagulation. These drugs include agents that inhibit activated factor X (FXa)
      (such as apixaban and rivaroxaban) or thrombin (such as dabigatran), and are
      collectively known today as non-VKA oral anticoagulants (NOACs). Since bleeding
      is the most common and most dangerous side effect of long-term anticoagulation,
      and because NOACs have very different mechanisms of action and pharmacokinetics
      compared with VKA, physicians are naturally concerned about the lack of
      experience regarding frequency, management and outcome of NOAC-associated
      bleeding in daily care. This review appraises trial and registry (or "real
      world") data pertaining to bleeding complications in patients taking NOACs and
      VKA and provides practical recommendations for the management of acute bleeding
      situations. 

PMID- 25940652
TI  - Modeling of Tracer Transport Delays for Improved Quantification of Regional
      Pulmonary 18F-FDG Kinetics, Vascular Transit Times, and Perfusion.
AB  - 18F-FDG-PET is increasingly used to assess pulmonary inflammatory cell activity.
      However, current models of pulmonary 18F-FDG kinetics do not account for delays
      in 18F-FDG transport between the plasma sampling site and the lungs. We developed
      a three-compartment model of 18F-FDG kinetics that includes a delay between the
      right heart and the local capillary blood pool, and used this model to estimate
      regional pulmonary perfusion. We acquired dynamic 18F-FDG scans in 12
      mechanically ventilated sheep divided into control and lung injury groups (n = 6
      each). The model was fit to tracer kinetics in three isogravitational regions-of
      interest to estimate regional lung transport delays and regional perfusion. 13NN
      bolus infusion scans were acquired during a period of apnea to measure regional
      perfusion using an established reference method. The delayed input function model
      improved description of 18F-FDG kinetics (lower Akaike Information Criterion) in
      98% of studied regions. Local transport delays ranged from 2.0 to 13.6 s,
      averaging 6.4 +/- 2.9 s, and were highest in non-dependent regions. Estimates of
      regional perfusion derived from model parameters were highly correlated with
      perfusion measurements based on 13NN-PET (R2 = 0.92, p < 0.001). By incorporating
      local vascular transports delays, this model of pulmonary 18F-FDG kinetics allows
      for simultaneous assessment of regional lung perfusion, transit times, and
      inflammation.

PMID- 25940653
TI  - Including family members in psychoeducation for bipolar disorder: is it worth it?

PMID- 25940655
TI  - Assessment of exposure to oak wood dust using gallic acid as a chemical marker.
AB  - OBJECTIVES: The American Conference of Governmental Industrial Hygienists (ACGIH)
      has classified oak dust as a human carcinogen (A1), based on increased sinus and
      nasal cancer rates among exposed workers. The aims of this study were to
      investigate the use of gallic acid (GA) as a chemical marker of occupational
      exposure to oak dusts, to develop a high-performance liquid chromatography-diode
      array detector method to quantify GA and to apply the method in the analysis of
      oak dust samples collected in several factories. METHODS: A high-performance
      liquid chromatography method was developed to detect GA in oak wood dust. The
      method was tested in the field, and GA was extracted from inhalable oak wood dust
      collected using the Institute of Occupational Medicine inhalable dust sampler in
      the air of five woodworking plants where only oak wood is used. RESULTS: A total
      of 57 samples with dust concentrations in the range of 0.27-11.14 mg/m(3) were
      collected. Five of these samples exceeded the Italian threshold limit value of 5
      mg/m(3), and 30 samples exceeded the ACGIH TLV of 1 mg/m(3). The GA
      concentrations were in the range 0.02-4.18 ug/m(3). The total oak dust sampled
      was correlated with the GA content with a correlation coefficient (r) of 0.95.
      CONCLUSIONS: The GA in the tannic extracts of oak wood may be considered a good
      marker for this type of wood, and its concentration in wood dust sampled in the
      work environment is useful in assessing the true exposure to carcinogenic oak
      dust.

PMID- 25940656
TI  - Clinical Practice Guideline on management of patients with diabetes and chronic
      kidney disease stage 3b or higher (eGFR <45 mL/min).

PMID- 25940654
TI  - Sources of input to the rostromedial tegmental nucleus, ventral tegmental area,
      and lateral habenula compared: A study in rat.
AB  - Profound inhibitory control exerted on midbrain dopaminergic neurons by the
      lateral habenula (LHb), which has mainly excitatory outputs, is mediated by the
      GABAergic rostromedial tegmental nucleus (RMTg), which strongly innervates
      dopaminergic neurons in the ventral midbrain. Early reports indicated that the
      afferent connections of the RMTg, excepting its very strong LHb inputs, do not
      differ appreciably from those of the ventral tegmental area (VTA). Presumably,
      however, the RMTg contributes more to behavioral synthesis than to simply invert
      the valence of the excitatory signal coming from the LHb. Therefore, the present
      study was done to directly compare the inputs to the RMTg and VTA and, in
      deference to its substantial involvement with this circuitry, the LHb was also
      included in the comparison. Data indicated that, while the afferents of the RMTg,
      VTA, and LHb do originate within the same large pool of central nervous system
      (CNS) structures, each is also related to structures that project more strongly
      to it than to the others. The VTA gets robust input from ventral striatopallidum
      and extended amygdala, whereas RMTg biased inputs arise in structures with a more
      direct impact on motor function, such as deep layers of the contralateral
      superior colliculus, deep cerebellar and several brainstem nuclei, and, via a
      relay in the LHb, the entopeduncular nucleus. Input from the ventral pallidal
      lateral preoptic-lateral hypothalamus continuum is strong in the RMTg and VTA and
      dominant in the LHb. Axon collateralization was also investigated, providing
      additional insights into the organization of the circuitry of this important
      triad of structures.

PMID- 25940657
TI  - Synthesis and Structure of a New Copper(II) Coordination Polymer Alternately
      Bridged by Oxamido and Carboxylate Groups: Evaluation of DNA/BSA Binding and
      Cytotoxic Activities.
AB  - A new one-dimensional (1D) copper(II) coordination polymer {[Cu2
      (dmaepox)(dabt)](NO3) . 0.5 H2 O}n , where H3 dmaepox and dabt denote N-benzoato
      N'-(3-methylaminopropyl)oxamide and 2,2'-diamino-4,4'-bithiazole, respectively,
      was synthesized and characterized by single-crystal X-ray diffraction and other
      methods. The crystal structure analysis revealed that the two copper(II) ions are
      bridged alternately by cis-oxamido and carboxylato groups to form a 1-D
      coordination polymer with the corresponding Cu . . . Cu separations of 5.1946(19)
      and 5.038(2) A. There is a three-dimensional supramolecular structure constructed
      by hydrogen bonding and pi-pi stacking interactions in the crystal. The
      reactivity towards herring sperm DNA (HS-DNA) and bovine serum albumin (BSA)
      indicated that the copper(II) polymer can interact with the DNA in the mode of
      intercalation, and bind to BSA responsible for quenching of tryptophan
      fluorescence by the static quenching mechanism. The in vitro cytotoxicity
      suggested that the copper(II) polymer exhibits cytotoxic effects against the
      selected tumor cell lines.

PMID- 25940658
TI  - Pharmacotherapy for leishmaniasis in the United States: focus on miltefosine.
AB  - Leishmaniasis is a protozoan infection native to various countries, including
      those in South America and Southeast Asia. Although the incidence of
      leishmaniasis is low in the United States, it is an important cause of infection
      in individuals traveling to endemic areas. Various treatment modalities are
      available, depending on their availability in the geographic region. In the
      United States, the treatment of choice is considered to be liposomal
      amphotericin, although other therapies have been explored. In 2014, miltefosine
      became the first orally available medication approved for the treatment of
      leishmaniasis in the United States. Based on available data, miltefosine is a
      first-line option for the treatment of leishmaniasis. Miltefosine is equally
      efficacious to and may be as tolerable as liposomal amphotericin B. The most
      common adverse effects of miltefosine are vomiting, diarrhea, and transient liver
      enzyme level elevation. Miltefosine has not been readily available in the United
      States due to marketing delays and is expected to become available later this
      year. In the meantime, the drug may be obtained through the Centers for Disease
      Control and Prevention expanded-access investigational new drug protocol. 

PMID- 25940659
TI  - Ultrahigh-capacity non-periodic photon sieves operating in visible light.
AB  - Miniaturization of optical structures makes it possible to control light at the
      nanoscale, but on the other hand it imposes a challenge of accurately handling
      numerous unit elements in a miniaturized device with aperiodic and random
      arrangements. Here, we report both the new analytical model and experimental
      demonstration of the photon sieves with ultrahigh-capacity of subwavelength holes
      (over 34 thousands) arranged in two different structural orders of randomness and
      aperiodicity. The random photon sieve produces a uniform optical hologram with
      high diffraction efficiency and free from twin images that are usually seen in
      conventional holography, while the aperiodic photon sieve manifests sub
      diffraction-limit focusing in air. A hybrid approach is developed to make the
      design of random and aperiodic photon sieve viable for high-accuracy control of
      the amplitude, phase and polarization of visible light. The polarization
      independence of the photon sieve will also greatly benefit its applications in
      optical imaging and spectroscopy. 

PMID- 25940660
TI  - Neuroprotective effect of Allium cepa L. in aluminium chloride induced
      neurotoxicity.
AB  - The present study was envisaged to investigate the neuroprotective potential of
      Allium cepa (A. cepa) in aluminium chloride induced neurotoxicity. Aluminium
      chloride (50 mg/kg/day) was administered orally in mice supplemented with
      different doses of A. cepa hydroethanolic extract for a period of 60 days.
      Various behavioural, biochemical and histopathological parameters were estimated
      in aluminium exposed animals. Chronic aluminium administration resulted in
      significant motor incoordination and memory deficits, which were also endorsed
      biochemically as there was increased oxidative stress as well as elevated
      acetylcholinesterase (AChE) and aluminium levels in the brain. Supplementation
      with A. cepa in aluminium exposed animals significantly improved muscle
      coordination and memory deficits as well as reduced oxidative stress, AChE and
      decreased abnormal aluminium deposition in the brain. Histopathologically, there
      was marked deterioration visualized as decreased vacuolated cytoplasm as well as
      decreased pyramidal cells in the hippocampal area of mice brain which were found
      to be reversed with A. cepa supplementation. Administration of BADGE (PPARgamma
      antagonist) in aluminium exposed animals reversed the neuroprotective potential
      of A. cepa as assessed with various behavioural, biochemical, neurochemical and
      histopathological estimations. In conclusion, finding of this study suggested
      significant neuroprotective potential of A. cepa in aluminium induced
      neurotoxicity. Further, the role of PPARgamma receptor agonism has also been
      suggested as a putative neuroprotective mechanism of A. cepa, which needs further
      studies for confirmation.

PMID- 25940661
TI  - Recombinant erythroid differentiation regulator 1 inhibits both inflammation and
      angiogenesis in a mouse model of rosacea.
AB  - The erythroid differentiation regulator 1 (Erdr1), which is a novel and highly
      conserved factor, was recently reported to be negatively regulated by IL-18 and
      to play a crucial role as an antimetastatic factor. IL-18 is a proinflammatory
      cytokine that functions as an angiogenic mediator in inflammation. Rosacea is a
      chronic inflammatory skin disorder that is characterized by abnormal inflammation
      and vascular hyperactivity of the facial skin. To determine whether Erdr1
      contributes to the regulation of the chronic inflammatory process in the
      development of rosacea, an immunohistochemical analysis was performed in healthy
      donors and patients with rosacea. In this study, we showed that Erdr1 was
      downregulated, whereas IL-18 was upregulated, in patients with rosacea, which led
      us to question the role of Erdr1 in this disorder. Moreover, a rosacea-like
      BALB/c mouse model was used to determine the role of Erdr1 in rosacea in vivo. LL
      37 injection induced typical rosacea features, including erythema, telangiectasia
      and inflammation. Treatment with recombinant Erdr1 (rErdr1) resulted in a
      significant reduction of erythema, inflammatory cell infiltration (including
      CD4(+) and CD8(+) T cells), and microvessel density with vascular endothelial
      growth factor (VEGF). Taken together, our findings suggest that rErdr1 may be
      involved in attenuating the inflammation and angiogenesis associated with the
      pathogenesis of rosacea. Thus, these results provide new insight into the
      mechanism involved in this condition and indicate that rErdr1 could be a
      potential target for therapeutic intervention of rosacea. 

PMID- 25940662
TI  - Myhre-LAPs syndrome and intubation related airway stenosis: keys to diagnosis and
      critical therapeutic interventions.
AB  - OBJECTIVES: Myhre-LAPS syndrome is a recently recognized disease caused by a
      mutation in the SMAD4 gene. This results in a range of pathology including
      laryngotracheal stenosis, arthropathy, prognathism and short stature, or LAPS
      syndrome. We aim to delineate the role of intubation in development of airway
      stenosis in these patients as well as provide insight into diagnosis and
      management of this syndrome. Herein we present four patients with Myhre-LAPS
      syndrome complicated by airway stenosis and perform a systematic review of all
      cases of Myhre-LAPS syndrome with reported airway pathology. STUDY DESIGN:
      Retrospective review METHODS: All patients diagnosed with Myhre-LAPS syndrome and
      airway stenosis at a single institution from 1981 to 2014 were reviewed. RESULTS:
      Four patients (4F, median age 42) were identified that met inclusion criteria.
      Initial presenting signs included progressive shortness of breath, dyspnea on
      exertion and respiratory distress. All four (100%) patients had multi-level
      airway stenosis most commonly in the subglottic and glottic regions and all
      patients had undergone at least one endotracheal intubation prior to
      presentation. One patient with a history of nasal tracheal intubation presented
      with nasal obstruction and was found to have choanal as well as subglottic
      stenosis. Two of the four (50%) patients are tracheostomy tube dependent, 1/4
      (25%) died of a fatal cardiac arrhythmia and 1/4 (25%) has had 6 endoscopic
      treatments for subglottic stenosis in 4 years with rapid symptom recurrence.
      CONCLUSIONS: Myhre-LAPS syndrome is characterized by progressive systemic
      fibrosis and patients are diagnosed by characteristic findings of prognathism,
      short stature, abnormal facies, and thick skin among other abnormalities. Airway
      management is complicated by recurrent, refractory subglottic stenosis often
      preceded by elective intubation as well as maxillary hypoplasia, trismus, and
      limited neck extension. Endotracheal intubation and surgical intervention should
      be approached with caution in these patients and multidisciplinary care teams are
      necessary to address all manifestations of this syndrome.

PMID- 25940663
TI  - Promising gaseous and electrochemical hydrogen storage properties of porous Mg-Pd
      films under mild conditions.
AB  - In this paper, the gaseous and electrochemical hydrogen storage properties of 200
      nm Mg-Pd thin films with different morphologies have been investigated. The
      results show that Mg-Pd films become porous with the increase of substrate
      temperature. Porous Mg-Pd films exhibit superior gaseous and electrochemical
      hydrogen storage behaviors under mild conditions, including rapid hydrogen
      sorption kinetics, a large hydrogen storage amount, high electrochemical
      discharge capacity, and a fast hydrogen diffusion rate. The excellent behaviors
      of porous Mg-Pd films might be ascribed to the significantly shortened hydrogen
      diffusion paths and the large contact areas between the hydrogen gas and the
      solid Mg phases, which are elucidative for the development and applications of
      thick Mg-Pd films. 

PMID- 25940664
TI  - MR Imaging of the Lumbosacral Plexus: A Review of Techniques and Pathologies.
AB  - The lumbosacral plexus is a complex anatomic area that serves as the conduit of
      innervation and sensory information to and from the lower extremities. It is
      formed by the ventral rami of the lumbar and sacral spine which then combine into
      larger nerves serving the pelvis and lower extremities. It can be a source of
      severe disability and morbidity for patients when afflicted with pathology.
      Patients may experience motor weakness, sensory loss, and/or debilitating pain.
      Primary neurologic processes can affect the lumbosacral plexus in both genetic
      and acquired conditions and typically affect the plexus and nerves symmetrically.
      Additionally, its unique relationship to the pelvic musculature and viscera
      render it vulnerable to trauma, infection, and malignancy. Such conditions are
      typically proceeded by a known history of trauma or established pelvic malignancy
      or infection. Magnetic resonance imaging is an invaluable tool for evaluation of
      the lumbosacral plexus due to its anatomic detail and sensitivity to pathologic
      changes. It can identify the cause for disability, indicate prognosis for
      improvement, and be a tool for delivery of interventions. Knowledge of proper MR
      protocols and imaging features is key for appropriate and timely diagnosis. Here
      we discuss the relevant anatomy of the lumbosacral plexus, appropriate imaging
      techniques for its evaluation, and discuss the variety of pathologies that may
      afflict it. 

PMID- 25940665
TI  - An improvised pressure gauge for regional nerve blockade/anesthesia injections:
      an initial study.
AB  - High injection pressure is one of the warning signs of intraneural injection,
      with animal models suggesting pressures higher than 69 or 176 kPa as high risk,
      and is normally detected subjectively and inaccurately. We describe a system
      improvised from common clinical components that uses Boyle's law to objectively
      measure injection pressure. The objectives of the study were to (1) Validate our
      improvised pressure gauge (IPG) by comparing the injection pressure as calculated
      by Boyle's law against the measured pressure and (2) Use the IPG to measure the
      range of injection pressures by two groups of anesthetic professionals using the
      "syringe feel" technique. Our IPG system consists of an extended 1 ml syringe
      attached to a 3-way stopcock, inserted between the syringe containing the local
      anesthetic injectate and the needle. The IPG was validated against a pressure
      calibration reference. 20 anesthesiologists and 20 anesthetic assistants were
      recruited to apply pressure to the 20 ml syringe in vitro while blinded to the
      attached IPG. The pressures were measured on three separate occasions for each
      participant. There was good agreement (<8 percent difference) between the
      measured and theoretical pressure values. Anesthesiologists exceeded the
      threshold of 69 kPa in 18 of a total of 60 attempts whereas anesthetic assistants
      exceeded the threshold in 30 attempts out of 60 attempts. Anesthetic assistants
      exerted a higher overall pressure of 80 kPa compared to 51 kPa for
      anesthesiologists-this was statistically significant (p = 0.027). Our improvised
      system is easily and rapidly assembled from common clinical equipment and shows
      promise as a monitor for inadvertent intraneural injection. 

PMID- 25940666
TI  - Metabolic clues to salubrious longevity in the brain of the longest-lived rodent:
      the naked mole-rat.
AB  - Naked mole-rats (NMRs) are the oldest-living rodent species. Living underground
      in a thermally stable ecological niche, NMRs have evolved certain exceptional
      traits, resulting in sustained health spans, negligible cognitive decline, and a
      pronounced resistance to age-related disease. Uncovering insights into mechanisms
      underlying these extraordinary traits involved in successful aging may
      conceivably provide crucial clues to extend the human life span and health span.
      One of the most fundamental processes inside the cell is the production of ATP,
      which is an essential fuel in driving all other energy-requiring cellular
      activities. Not surprisingly, a prominent hallmark in age-related diseases, such
      as neurodegeneration and cancer, is the impairment and dysregulation of metabolic
      pathways. Using a two-dimensional polyacrylamide gel electrophoresis proteomics
      approach, alterations in expression and phosphorylation levels of metabolic
      proteins in the brains of NMRs, aged 2-24 years, were evaluated in an age
      dependent manner. We identified 13 proteins with altered levels and/or
      phosphorylation states that play key roles in various metabolic pathways
      including glycolysis, beta-oxidation, the malate-aspartate shuttle, the
      Tricarboxylic Acid Cycle (TCA) cycle, the electron transport chain, NADPH
      production, as well as the production of glutamate. New insights into potential
      pathways involved in metabolic aspects of successful aging have been obtained by
      the identification of key proteins through which the NMR brain responds and
      adapts to the aging process and how the NMR brain adapted to resist age-related
      degeneration. This study examines the changes in the proteome and phosphoproteome
      in the brain of the naked mole-rat aged 2-24 years. We identified 13 proteins
      (labeled in red) with altered expression and/or phosphorylation levels that are
      conceivably associated with sustained metabolic functions in the oldest NMRs that
      may promote a sustained health span and life span.

PMID- 25940668
TI  - "First, know thyself": cognition and error in medicine.
AB  - Although error is an integral part of the world of medicine, physicians have
      always been little inclined to take into account their own mistakes and the
      extraordinary technological progress observed in the last decades does not seem
      to have resulted in a significant reduction in the percentage of diagnostic
      errors. The failure in the reduction in diagnostic errors, notwithstanding the
      considerable investment in human and economic resources, has paved the way to new
      strategies which were made available by the development of cognitive psychology,
      the branch of psychology that aims at understanding the mechanisms of human
      reasoning. This new approach led us to realize that we are not fully rational
      agents able to take decisions on the basis of logical and probabilistically
      appropriate evaluations. In us, two different and mostly independent modes of
      reasoning coexist: a fast or non-analytical reasoning, which tends to be largely
      automatic and fast-reactive, and a slow or analytical reasoning, which permits to
      give rationally founded answers. One of the features of the fast mode of
      reasoning is the employment of standardized rules, termed "heuristics."
      Heuristics lead physicians to correct choices in a large percentage of cases.
      Unfortunately, cases exist wherein the heuristic triggered fails to fit the
      target problem, so that the fast mode of reasoning can lead us to unreflectively
      perform actions exposing us and others to variable degrees of risk. Cognitive
      errors arise as a result of these cases. Our review illustrates how cognitive
      errors can cause diagnostic problems in clinical practice. 

PMID- 25940669
TI  - Large Congenital Melanocytic Nevus on the Breast Sparing the Nipple and Areola.
AB  - BACKGROUND: Divided nevus is a rare entity that has been described for a special
      appearance of congenital melanocytic nevi (CMNs) occurring on the eyelid and
      penis. It is presumed that the formation of divided nevi is related with the
      embryologic development of the eyelid and penis, thus giving a hint about the
      occurrence time of CMN in utero. This article focuses on a formerly undescribed
      observation of another special clinical appearance of CMN discussing possible
      relation with embryogenesis. METHODS: The data including photographic
      documentations of a total number of 86 patients with large CMN seen in a single
      center were reviewed according to the involvement of the nipple and areola by the
      main mass of the nevus and associated satellite lesions. RESULTS: Eight patients
      presented with CMNs involving one (n=6) or both (n=2) breast region. In all of
      them, CMN surrounded the nipple-areola complex without involving these
      structures. Furthermore, satellite nevi have not been observed on the nipple and
      areola in any of the 86 patients. CONCLUSION: We presume that different
      developmental time periods of the breast and the nipple-areola complex and the
      occurrence of the melanocytic lesion before the embryologic development of nipple
      areola complex could explain our observation of CMN sparing the nipple-areola
      complex. The term "nipple-sparing nevus of the breast" is suggested for this
      special clinical appearance of CMN.

PMID- 25940670
TI  - Matrix metalloproteinases and endothelial dysfunction: The search for new
      prognostic markers and for new therapeutic targets for vascular wall imbalance.

PMID- 25940671
TI  - Can a near win kindle motivation? The impact of nearly winning on motivation for
      unrelated rewards.
AB  - Common intuition and research suggest that winning is more motivating than
      losing. However, we propose that just failing to obtain a reward (i.e., nearly
      winning it) in one task leads to broader, positive motivational effects on
      subsequent unrelated tasks relative to clearly losing or actually obtaining the
      reward. We manipulated a near-win experience using a game app in Experiments 1
      through 3 and a lottery in Experiment 4. Our findings showed that nearly winning
      in one task subsequently led participants to walk faster to get to a chocolate
      bar (Experiment 1), salivate more for money (Experiment 2), and increase their
      effort to earn money in a card-sorting task (Experiment 3). A field study
      (Experiment 4) demonstrated that nearly winning led people to subsequently spend
      more money on desirable consumer products. Finally, our findings showed that when
      the activated motivational state was dampened in an intervening task, the nearly
      winning effect was attenuated. 

PMID- 25940672
TI  - Bacterial urinary tract infections associated with transitional cell carcinoma in
      dogs.
AB  - BACKGROUND: Urinary tract infections (UTI) are believed to be common in dogs with
      transitional cell carcinoma (TCC), but incidence and contributing factors have
      not been reported. OBJECTIVES: To determine the frequency and bacterial agents
      associated with UTI in dogs with TCC and define contributing factors. ANIMALS:
      Eighty-five dogs with a history of urogenital TCC undergoing treatment with
      chemotherapy that had at least 1 urine culture performed. METHODS: Medical
      records and culture results were retrospectively reviewed and ultrasound images
      were reviewed when available. Clinical factors were evaluated statistically for
      association with positive culture. RESULTS: Fifty-five percent (47/85) of dogs
      had at least 1 positive culture during the course of treatment. Female dogs (80%,
      40/50) were more likely than male dogs (29%, 10/35) to have at least 1 positive
      culture. Ultrasound examination determined that female dogs were more likely to
      have urethral (74%, 31/42) or trigonal tumor involvement (71%, 30/42) compared to
      male dogs (32%, 9/28 and 43%, 12/28, respectively). The most commonly isolated
      organisms were Staphylococcus spp. (23.9%, 29/121) and Escherichia coli (19.8%,
      24/121). Dogs with urethral involvement of TCC were significantly more likely to
      have at least 1 positive culture than dogs without urethral involvement (75%,
      30/40 versus 30%, 9/30). CONCLUSIONS: Urinary tract infection is common in dogs
      with TCC highlighting the importance of regular monitoring for bacterial cystitis
      in dogs with TCC. In addition, clinical factors such as tumor location and sex
      may be predictive of positive culture and can help clinicians assess the risk of
      UTI.

PMID- 25940673
TI  - Major histocompatibility complex similarity and sexual selection: different does
      not always mean attractive.
AB  - Females that mate multiply have the possibility to exert postcopulatory choice
      and select more compatible sperm to fertilize eggs. Prior work suggests that
      dissimilarity in major histocompatibility complex (MHC) plays an important role
      in determining genetic compatibility between partners. Favouring a partner with
      dissimilar MHC alleles would result in offspring with high MHC diversity and
      therefore with enhanced survival thanks to increased resistance to pathogens and
      parasites. The high variability of MHC genes may further allow discrimination
      against the sperm from related males, reducing offspring homozygosity and
      inbreeding risk. Despite the large body of work conducted at precopulatory level,
      the role of MHC similarity between partners at postcopulatory level has been
      rarely investigated. We used an internal fertilizing fish with high level of
      multiple matings (Poecilia reticulata) to study whether MHC similarity plays a
      role in determining the outcome of fertilization when sperm from two males
      compete for the same set of eggs. We also controlled for genomewide similarity by
      determining similarity at 10 microsatellite loci. Contrary to prediction, we
      found that the more MHC-similar male sired more offspring while similarity at the
      microsatellite loci did not predict the outcome of sperm competition. Our results
      suggest that MHC discrimination may be involved in avoidance of hybridization or
      outbreeding rather than inbreeding avoidance. This, coupled with similar findings
      in salmon, suggests that the preference for MHC-dissimilar mates is far from
      being unanimous and that pre- and postcopulatory episodes of sexual selection can
      indeed act in opposite directions. 

PMID- 25940667
TI  - The dormant blood microbiome in chronic, inflammatory diseases.
AB  - Blood in healthy organisms is seen as a 'sterile' environment: it lacks
      proliferating microbes. Dormant or not-immediately-culturable forms are not
      absent, however, as intracellular dormancy is well established. We highlight here
      that a great many pathogens can survive in blood and inside erythrocytes. 'Non
      culturability', reflected by discrepancies between plate counts and total counts,
      is commonplace in environmental microbiology. It is overcome by improved
      culturing methods, and we asked how common this would be in blood. A number of
      recent, sequence-based and ultramicroscopic studies have uncovered an authentic
      blood microbiome in a number of non-communicable diseases. The chief origin of
      these microbes is the gut microbiome (especially when it shifts composition to a
      pathogenic state, known as 'dysbiosis'). Another source is microbes translocated
      from the oral cavity. 'Dysbiosis' is also used to describe translocation of cells
      into blood or other tissues. To avoid ambiguity, we here use the term
      'atopobiosis' for microbes that appear in places other than their normal
      location. Atopobiosis may contribute to the dynamics of a variety of inflammatory
      diseases. Overall, it seems that many more chronic, non-communicable,
      inflammatory diseases may have a microbial component than are presently
      considered, and may be treatable using bactericidal antibiotics or vaccines. 

PMID- 25940674
TI  - Genome-wide mapping of DNA hydroxymethylation in osteoarthritic chondrocytes.
AB  - OBJECTIVE: To examine the genome-wide distribution of hydroxymethylated cytosine
      (5hmC) in osteoarthritic (OA) and normal chondrocytes in order to investigate the
      effect on OA-specific gene expression. METHODS: Cartilage was obtained from OA
      patients undergoing total knee arthroplasty or from control patients undergoing
      anterior cruciate ligament reconstruction. Genome-wide sequencing of 5hmC
      enriched DNA was performed in a small cohort of normal and OA chondrocytes to
      identify differentially hydroxymethylated regions (DhMRs) in OA chondrocytes.
      Data from the genome-wide sequencing of 5hmC-enriched DNA were intersected with
      global OA gene expression data to define subsets of genes and pathways
      potentially affected by increased 5hmC levels in OA chondrocytes. RESULTS: A
      total of 70,591 DhMRs were identified in OA chondrocytes as compared to normal
      chondrocytes, 44,288 (63%) of which were increased in OA chondrocytes. The
      majority of DhMRs (66%) were gained in gene bodies. Increased DhMRs were observed
      in ~50% of genes previously implicated in OA pathology including MMP3, LRP5,
      GDF5, and COL11A1. Furthermore, analyses of gene expression data revealed gene
      body gain of 5hmC appears to be preferentially associated with activated, but not
      repressed, genes in OA chondrocytes. CONCLUSION: This study provides the first
      genome-wide profiling of 5hmC distribution in OA chondrocytes. We had previously
      reported a global increase in 5hmC levels in OA chondrocytes. Gain of 5hmC in the
      gene body is found to be characteristic of activated genes in OA chondrocytes,
      highlighting the influence of 5hmC as an epigenetic mark in OA. In addition, this
      study identifies multiple OA-associated genes that are potentially regulated
      either singularly by gain of DNA hydroxymethylation or in combination with loss
      of DNA methylation.

PMID- 25940675
TI  - Pharmacokinetics and pharmacodynamics of PF-05231023, a novel long-acting FGF21
      mimetic, in a first-in-human study.
AB  - AIMS: The aim of the present study was to evaluate the
      pharmacokinetics/pharmacodynamics (PK/PD), safety and tolerability of single
      intravenous (IV) doses of PF-05231023, a long acting fibroblast growth factor 21
      (FGF21) analogue being developed for the treatment of type 2 diabetes mellitus
      (T2DM). METHODS: T2DM subjects (glycosylated haemoglobin: 7.0-10.5%; on stable
      metformin therapy and/or diet and exercise) were randomized to receive a single
      dose of placebo or PF-05231023 (0.5-200 mg). Safety evaluations were performed up
      to 14 days after dosing. PK and PD endpoints were measured and a PK/PD model was
      developed for triglyceride - an early marker of drug activity. RESULTS: No
      antidrug antibody or serious adverse events (AEs) were observed. The most
      frequent AEs were gastrointestinal but were generally mild. Plasma PF-05231023
      levels peaked immediately post-IV dosing, with mean terminal half-lives of 6.5
      7.7 h and 66.5- 96.6 h for intact C- and N-termini, respectively. Intact C
      terminus exposures increased proportionally with increasing dose, whereas N
      terminus exposures appeared to trend higher than dose-proportionally. Although no
      apparent effect on plasma glucose was seen, dose-dependent decreases in
      triglyceride were observed, with a maximum reduction of 48.5 +/- 10.0% (mean +/-
      standard deviation) for the 200 mg dose compared with a reduction of 19.1 +/-
      26.4% for placebo, demonstrating proof of pharmacology. Moreover, a reduction in
      total cholesterol and low-density lipoprotein cholesterol and an increase in high
      density lipoprotein cholesterol were observed in the high-dose groups.
      CONCLUSIONS: Single IV doses of PF-05231023 up to 200 mg were generally safe and
      well tolerated by subjects with T2DM. The observed early sign of pharmacology
      supports further clinical testing of PF-05231023 upon repeated administration.

PMID- 25940676
TI  - Molecular characterization of outer membrane vesicles released from Acinetobacter
      radioresistens and their potential roles in pathogenesis.
AB  - Acinetobacter radioresistens is an important member of genus Acinetobacter from a
      clinical point of view. In the present study, we report that a clinical isolate
      of A. radioresistens releases outer membrane vesicles (OMVs) under in vitro
      growth conditions. OMVs were released in distinctive size ranges with diameters
      from 10 to 150 nm as measured by the dynamic light scattering (DLS) technique.
      Additionally, proteins associated with or present into OMVs were identified using
      LC-ESI-MS/MS. A total of 71 proteins derived from cytosolic, cell membrane,
      periplasmic space, outer membrane (OM), extracellular and undetermined locations
      were found in OMVs. The initial characterization of the OMV proteome revealed a
      correlation of some proteins to biofilm, quorum sensing, oxidative stress
      tolerance, and cytotoxicity functions. Thus, the OMVs of A. radioresistens are
      suggested to play a role in biofilm augmentation and virulence possibly by
      inducing apoptosis.

PMID- 25940678
TI  - One-step synthesis of a cyclic 2,17-dioxo[3,3](4,4') biphenylophane and first
      preparation of a microporous polymer network from a macrocyclic precursor by
      cyclotrimerization.
AB  - One-step synthesis of a cyclic 2,17-dioxo[3,3](4,4')biphenylophane (MC) was
      achieved in high yield; its structure was verified by single crystal X-ray
      analysis. As a first example, a microporous polymer network was formed from
      macrocycle MC via acid-catalysed cyclotrimerization yielding a BET surface area
      of ca. 570 m(2) g(-1). 

PMID- 25940677
TI  - Primary bilateral diffuse large B-cell lymphoma of the adrenals.

PMID- 25940679
TI  - Study on the adult physique with the Heath-Carter anthropometric somatotype in
      the Han of Xi'an, China.
AB  - The study of somatotypes has important significance for medical and physical
      anthropology as well as sports science. The aim of this study was to understand
      the somatotype components of the Han population in Xi'an and compare the
      somatotypes of the Han and five other nationalities in China. The study sample
      consisted of 429 people of Han nationality (207 males, 222 females) from Xi'an,
      China, aged >=20 years old. The Heath-Carter anthropometric method was employed.
      We evaluated the differences in age and sex by one-way ANOVA and t test. A
      comparison of somatotypes between the Han and other nationalities was made using
      the U test. The results showed that the male and female samples all could be
      classified as having a mesomorphic endomorph profile. The difference in
      endomorphy was strongest between sexes in all age groups (P < 0.01). There were
      prominent differences in mesomorphy and ectomorphy between males and females in
      the 50-59- and >=60-year-old age groups. In females, the differences in
      somatotype components appeared to be distinguished between ages (P < 0.01 or P <
      0.05). However, in males, there were prominent differences in somatotype
      components between the 20-29 year olds and all other age groups (P < 0.01 or P <
      0.05) except for between those 20-29 and >=60 years old in endomorphy. Compared
      with the other five nationalities, there were prominent differences in somatotype
      components between males and females. These results suggest that the somatotype
      of the Han population in Xi'an, China, has a predominantly mesomorphic endomorph
      profile. The endomorphic component shows distinct differences between ages and
      genders, respectively. Additionally, there are distinct differences in the
      somatotype components between Xi'an Han and five other nationalities in China in
      males and females. 

PMID- 25940680
TI  - Spatial clusters of constitutively active neurons in mouse visual cortex.
AB  - The networks of neocortical neurons are coordinated by spontaneous activity, the
      level of which exhibits high heterogeneity among neurons, ranging from low
      activity levels to very high activity levels, even in the same network. Highly
      active neurons represent a small proportion in the cerebral cortex and are
      mingled in a web of the vast majority of neurons with low firing rates. However,
      little is known about the spatial arrangement of these highly active cells within
      the cerebral cortex. Here, we visualized their spatial distribution by labeling
      them with c-Fos, a neuronal activity marker, in the mouse primary visual cortex.
      By introducing energy-like and entropy-like parameters that did not require
      arbitrary thresholds for c-Fos positivity, we found that strongly c-Fos
      expressing neurons were clustered in the vicinity. The cluster size measured
      approximately 100 MUm in diameter and was smaller in layer 2/3 than in layers 5
      and 6. Layer 1 neurons did not exhibit a clustered pattern of c-Fos-expressing
      neurons. Our novel statistical approaches are not subject to human bias and are
      thus widely applicable to evaluate the spatial bias of any particles. 

PMID- 25940681
TI  - A quantitative approach for studying the bioactivity of nanohydroxyapatite/gold
      composites.
AB  - This work describes a quantitative kinetic approach to assess the in vitro
      bioactivity of gold-doped hydroxyapatite-polyvinyl alcohol nanocomposites. The
      surface morphology of the in situ prepared nanocomposites as characterized by
      transmission electron microscopy (TEM) revealed a rod-like shape. Differential
      thermal analysis-thermogravimetric (DTA-TG), and fourier transformed infrared
      spectroscopy (FTIR) as well as zeta potential measurements of the prepared
      nanocomposites were carried out. Uptake profiles of Ca and P were studied onto
      nanocomposites of different gold concentrations after their soaking in simulated
      body fluid and they best followed the pseudo second-order kinetic model. The
      highest uptakes of both Ca and P were obtained using the nanocomposite with the
      lowest concentration of gold. Furthermore, sorption mechanism was described by
      the intraparticle diffusion model where pore diffusion was found to be the rate
      limiting step. The prepared nanocomposites have promising potential in orthopedic
      and tissue engineering applications because of their high capacity and fast
      uptake for Ca and P, which form apatite.

PMID- 25940682
TI  - Synthesis of 2-Alkoxyaryl-2-aryl Enamines via Tandem Copper-Catalyzed
      Cycloaddition and Rhodium-Catalyzed Alkoxyarylation from Alkynes, N-Sulfonyl
      Azides, and Aryl Ethers.
AB  - A synthetic route to a wide range of 2-alkoxyaryl-2-aryl enamines is developed
      from Rh-catalyzed alkoxyarylation of N-sulfonyl-4-aryl-1,2,3-triazoles with aryl
      ethers via the elimination of nitrogen molecule. In addition, 2-alkoxyaryl-2-aryl
      enamines are prepared via tandem Cu-catalyzed cycloaddition and Rh-catalyzed
      alkoxyarylation starting from alkynes, N-sulfonyl azides, and aryl ethers in one
      pot. 

PMID- 25940683
TI  - A donor-acceptor conjugated block copolymer of poly(arylenevinylene)s by ring
      opening metathesis polymerization.
AB  - Novel conjugated cyclophanes comprising electron donating cyclopentadithiophene
      vinylene and accepting dithienobenzothiadiazole-vinylene have been synthesized by
      McMurry coupling. Ring-opening metathesis polymerization (ROMP) of the acceptor
      monomer and the subsequent addition of the donor monomer allows the preparation
      of a fully conjugated diblock copolymer. The diblock copolymer exhibits multiple
      optical and electrochemical functions. 

PMID- 25940684
TI  - Concurrent and Predictive Validity of Arm Kinematics With and Without a Trunk
      Restraint During a Reaching Task in Individuals With Stroke.
AB  - OBJECTIVE: To examine the concurrent and predictive validity of measurements of
      kinematic variables during reaching tasks with and without a trunk constraint in
      individuals with stroke. DESIGN: Randomized controlled trials. SETTINGS:
      Hospitals and a laboratory. PARTICIPANTS: Individuals with stroke (N=95) enrolled
      in previous and ongoing clinical trials. INTERVENTIONS: Upper limb training
      protocols were 90 to 120 minutes of intervention every weekday for 3 to 4 weeks.
      MAIN OUTCOME MEASURES: Functional capacity was assessed using the Action Research
      Arm Test and motor impairment using the Fugl-Meyer Assessment for the Upper
      Extremity. Movement kinematics were measured during a reaching task with and
      without a trunk constraint. We derived 5 endpoint control variables and 3 joint
      recruitment variables for estimating concurrent and predictive validity. RESULTS:
      The adjusted R(2) values for the constraint tasks ranged from .24 to .38 and for
      the unconstraint tasks from .29 to .40. Movement time was the most prominent
      kinematic variable for the Fugl-Meyer Assessment for the Upper Extremity before
      and after the intervention (P<.05). For the Action Research Arm Test, movement
      time and endpoint displacement were the most significant variables before and
      after the intervention, respectively (P<.05). CONCLUSIONS: Measuring kinematic
      performance during an unconstrained task is appropriate and possibly sufficient
      to represent motor impairment and functional capacity of individuals with stroke.
      Movement time is the dominant variable associated with motor impairment and
      functional capacity, and endpoint displacement is unique in reflecting functional
      capacity of individuals with stroke.

PMID- 25940685
TI  - Multiple roles of hypoxia in ovarian function: roles of hypoxia-inducible factor
      related and -unrelated signals during the luteal phase.
AB  - There is increasing interest in the role of oxygen conditions in the
      microenvironment of organs because of the discovery of a hypoxia-specific
      transcription factor, namely hypoxia-inducible factor (HIF) 1. Ovarian function
      has several phases that change day by day, including ovulation, follicular growth
      and corpus luteum formation and regression. These phases are regulated by many
      factors, including pituitary hormones and local hormones, such as steroids,
      peptides and cytokines, as well as oxygen conditions. Hypoxia strongly induces
      angiogenesis because transcription of the potent angiogenic factor vascular
      endothelial growth factor (VEGF) is regulated by HIF1. Follicular development and
      luteal formation are accompanied by a marked increase in angiogenesis assisted by
      HIF1-VEGF signalling. Hypoxia is also one of the factors that induces luteolysis
      by suppressing progesterone synthesis and by promoting apoptosis of luteal cells.
      The present review focuses on recent studies of hypoxic conditions, as well as
      HIF1-regulated genes and proteins, in the regulation of ovarian function.

PMID- 25940686
TI  - Clinical presentation and outcome of patients with ST-segment elevation
      myocardial infarction without culprit angiographic lesions.
AB  - Patients diagnosed with ST-segment elevation myocardial infarction (STEMI) are
      occasionally found to have no culprit lesion on coronary angiography and are
      classified as presenting with false-positive STEMI. The clinical presentation and
      outcomes of these patients need to be further explored. In this case-controlled
      study, 259 consecutive patients with true code STEMI were compared to 104
      consecutive STEMI patients without culprit lesions on emergent coronary
      angiography. We compared the clinical presentation, electrocardiographic
      features, etiology, and outcomes of the two groups. STEMI patients without
      culprit lesions were less likely to have typical chest pain (46% vs. 79%, P <
      0.01). The ST-elevation in the group without culprit lesion was more likely to be
      concave (56% vs. 31%, P < 0.01), with less reciprocal ST-depression (19% vs. 71%,
      P < 0.01). The group without culprit lesions had a higher rate of ventilator
      support requirement (12.4% vs. 5.4%, P = 0.02), and higher rate of 30-day
      mortality (11.0% vs. 5.9%, P = 0.02). However, after excluding the patients with
      out-of-hospital cardiac arrests from both groups, the difference was no longer
      significant (P = 0.40 and 0.34 respectively). The relative poor outcomes of
      patients with false-positive code STEMI reflect the severity of their underlying
      medical condition. Careful history and review of ECG may help differentiate this
      group from true STEMI.

PMID- 25940688
TI  - Subtle structural changes in octupolar merocyanine dyes influence the
      photosensitized production of singlet oxygen.
AB  - The photophysical properties of two indoline-based octupolar merocyanine dyes and
      of the corresponding quinoline-based dyes were examined. This seemingly subtle
      structural change in the chromophore of these molecules has an appreciable effect
      on the yields with which these respective compounds sensitize the production of
      singlet molecular oxygen, O2(a(1)Deltag). The indoline-based dyes are reasonably
      efficient O2(a(1)Deltag) sensitizers (phiDelta ~ 0.35), whereas the quinoline
      based dyes are poor O2(a(1)Deltag) sensitizers (phiDelta ~ 0.005). A series of
      experiments, including Laser-Induced Optoacoustic Calorimetric (LIOAC)
      measurements, reveal that this difference principally reflects the fact that the
      excited singlet state of the quinoline-based dyes rapidly and efficiently decays
      via nonradiative channels to regenerate the ground state molecule. It is likely
      that a charge-transfer state mediates this efficient coupling between the excited
      and ground states. Such subtle, structure-dependent effects are important in
      elucidating and ultimately understanding phenomena that influence the efficiency
      of photosensitized O2(a(1)Deltag) production. In turn, the knowledge gained
      facilitates the rational design and preparation of O2(a(1)Deltag) sensitizers
      with explicitly controlled properties. 

PMID- 25940687
TI  - A post-partum single-dose TDF/FTC tail does not prevent the selection of NNRTI
      resistance in women receiving pre-partum ZDV and intrapartum single-dose
      nevirapine to prevent mother-to- child HIV-1 transmission.
AB  - Although the rates of vertical transmission of HIV in the developing world have
      improved to around 3% in countries like South Africa, resistance to
      antiretrovirals (ARV) used in Prevention of Mother-to-Child transmission (pMTCT)
      strategies may thwart such outcomes and affect the efficacy of future ARV
      regimens in mothers and children. This study conducted in Durban, South Africa,
      between 2010 and 2013 found a high rate of nevirapine (NVP) resistance among
      women receiving Zidovudine (AZT) from 14 weeks gestation, single dose nevirapine
      (sd NVP) at the onset of labor and a single dose of coformulated
      Tenofovir/Emtricitabine (TDF/FTC) postpartum. Using Sanger sequencing, high and
      intermediate levels of nevirapine (NVP) resistance were detected in 15/44 (34%)
      and in 1/44 (2%) of women tested, respectively. Most subjects selected the K103N
      mutation (22% (10/45) of all patients and 66% (10/15) of those with high-level
      NVP resistance). Such rate of NVP resistance is comparable to studies where only
      sd NVP was used. In conclusion, a post-partum single-dose TDF/FTC tail does not
      prevent the selection of NNRTI resistance in women receiving pre-partum ZDV and
      intrapartum sd NVP to prevent mother-to-child HIV-1 transmission.

PMID- 25940689
TI  - Diagnosing death.

PMID- 25940690
TI  - Salicylic acid elicitation during cultivation of the peppermint plant improves
      anti-diabetic effects of its infusions.
AB  - Peppermint (Mentha piperita) infusions represent an important source of bioactive
      compounds with health benefits, which can be enhanced by applying salicylic acid
      (SA) during plant cultivation. The aim of this study was to evaluate the effect
      of SA (0, 0.5 and 2 mM) during peppermint cultivation on the chemical profile of
      saponins and alkaloids, as well as the anti-diabetic properties of the resulting
      infusions. The results showed that a 2 mM SA treatment significantly improved the
      chemical profiles of the infusions. Furthermore, the administration of 2 mM SA
      treated peppermint infusions for 4 weeks to a high-fat diet/streptozotocin
      induced diabetic rats decreased serum glucose levels (up to 25%) and increased
      serum insulin levels (up to 75%) as compared with the diabetic control. This can
      be related to the observed protection on pancreatic beta-cells. Furthermore, 0.5
      and 2 mM SA-treated peppermint infusions decreased LDL (24 and 47%, respectively)
      and increased HDL levels (18 and 37%, respectively). In addition, all groups
      treated with peppermint infusions had lower serum and liver triglyceride
      contents, where 2 mM SA peppermint infusion showed the highest effect (44% and
      56%, respectively). This is probably caused by its higher capacity to inhibit
      pancreatic lipase activity and lipid absorption. Moreover, SA-treated peppermint
      infusions improved the steatosis score in diabetic rat liver and decreased serum
      transaminase levels, probably as a result of the increase in steroidal saponins
      and alkaloids, such as trigonellin. Therefore, the application of 2 mM SA during
      cultivation of peppermint could be used to improve the anti-diabetic properties
      of peppermint infusions.

PMID- 25940691
TI  - Systematic optimization of human pluripotent stem cells media using Design of
      Experiments.
AB  - Human pluripotent stem cells (hPSC) are used to study the early stages of human
      development in vitro and, increasingly due to somatic cell reprogramming,
      cellular and molecular mechanisms of disease. Cell culture medium is a critical
      factor for hPSC to maintain pluripotency and self-renewal. Numerous defined
      culture media have been empirically developed but never systematically optimized
      for culturing hPSC. We applied design of experiments (DOE), a powerful
      statistical tool, to improve the medium formulation for hPSC. Using pluripotency
      and cell growth as read-outs, we determined the optimal concentration of both
      basic fibroblast growth factor (bFGF) and neuregulin-1 beta 1 (NRG1beta1). The
      resulting formulation, named iDEAL, improved the maintenance and passage of hPSC
      in both normal and stressful conditions, and affected trimethylated histone 3
      lysine 27 (H3K27me3) epigenetic status after genetic reprogramming. It also
      enhances efficient hPSC plating as single cells. Altogether, iDEAL potentially
      allows scalable and controllable hPSC culture routine in translational research.
      Our DOE strategy could also be applied to hPSC differentiation protocols, which
      often require numerous and complex cell culture media. 

PMID- 25940692
TI  - Anti-oxidant profiles and markers of oxidative stress in preterm neonates.
AB  - BACKGROUND: Preterm birth is associated with an increased oxidant burden which
      places these infants at a higher risk of injury. AIMS: This prospective study
      aimed to assess levels of antioxidants and a marker of oxidative stress in
      preterm neonates. OBJECTIVES: (i) To compare levels of anti-oxidants [vitamin A,
      vitamin E, catalase, total anti-oxidant status (TAS)] as well as malondialdehyde
      level (MDA) (a marker of lipid peroxidation) between preterm and full-term
      neonates; (ii) to determine changes in the values of measured vitamins at birth
      and at discharge among preterm neonates; and (iii) to compare levels of anti
      oxidants with MDA levels in relation to complications of prematurity and outcome.
      METHODS: The study was undertaken in 100 preterm neonates and 100 full-term
      neonates as a control group. MDA was estimated by a thiobarbituric acid-reactive
      technique; TAS was determined using a Randox assay kit; catalase activity was
      measured spectrophotometrically and vitamin A and E levels were estimated by high
      performance liquid chromatography. RESULTS: The plasma levels of vitamin A,
      vitamin E, TAS and catalase were significantly lower in the preterm than in the
      full-term group (P < 0.01), and the plasma level of MDA was significantly higher
      in preterm than full-term neonates (P < 0.01). Vitamin A and E levels in preterm
      neonates were significantly higher at discharge than at birth (P < 0.01). Vitamin
      A, vitamin E and catalase levels at birth were significantly lower in patients
      who developed necrotizing enterocolitis or bronchopulmonary dysplasia than in
      those who did not. CONCLUSION: Preterm neonates are exposed to increased oxidant
      stress at birth and are susceptible to anti-oxidant deficiencies. A higher dose
      of enteral vitamin A supplementation in preterm neonates might reduce morbidity
      and improve outcome. Further studies are warranted to evaluate the appropriate
      dose of oral vitamin E supplementation for preterm neonates.

PMID- 25940693
TI  - Prevalence of normal TSH value among patients with autonomously functioning
      thyroid nodule.
AB  - BACKGROUND: International guidelines significantly diverge on the effectiveness
      of thyroid scintigraphy (TS) in the initial work-up of thyroid nodules. In
      particular, the role of TS to detect or exclude the presence of autonomously
      functioning thyroid nodules (AFTN) in patients with normal serum thyrotropin
      (TSH) is still a matter to debate. Here, we aimed to review the literature on the
      prevalence of normal TSH value among patients with AFTN and meta-analyse data of
      the retrieved eligible papers. MATERIALS AND METHODS: A comprehensive literature
      search of studies published from January 2000 to December 2014 on AFTN detected
      by TS was performed. Records reporting serum TSH values in AFTN were selected.
      Pooled prevalence of AFTN with normal TSH values was calculated on a per-patient
      analysis including 95% confidence intervals (95% CI). RESULTS: Eight records
      including 2761 AFTN were selected for the meta-analysis. Pooled prevalence of
      AFTN with normal TSH detected by TS was 50% (95% CI: 32-68%). Selection bias in
      the included studies and heterogeneity among studies were potential limitations
      of the meta-analysis. CONCLUSIONS: Present meta-analysis shows that about one in
      two patients with AFTN demonstrated by TS has a TSH value within normal
      references. As a consequence, TSH measurement may not be considered as effective
      as a single tool to detect or exclude AFTN, and TS remains mandatory.

PMID- 25940695
TI  - Non-invasive Measurements of Energy Expenditure and Respiratory Quotient by
      Respiratory Mass Spectrometry in Children on Extracorporeal Membrane Oxygenation
      A Pilot Study.
AB  - Extracorporeal membrane oxygenation (ECMO) provides temporary life-saving support
      for pediatric patients with severe cardiac failure, but causes metabolic
      disturbances and altered nutritional requirements. However, few studies have
      addressed the optimal energy supply to meet the demand of these children, largely
      due to technical difficulties with their invasive nature. We have adapted
      respiratory mass spectrometry to continuously measure O2 consumption and CO2
      production in the gas exchange across the ECMO oxygenator, as well as that across
      the ventilator. This study aimed to assess energy expenditure (EE) and
      respiratory quotient (RQ) in children on ECMO. Five children (aged 0.3 to 36
      months, median 20) were studied between Day 1 and Day 6 on ECMO. EE and RQ were
      measured in sequential fashion at the child's native lungs and ECMO oxygenator
      using respiratory mass spectrometry. Measurements were collected at 4-h
      intervals, with the means in 24 h representing the values of each day. Each
      child's caloric and protein intakes were recorded for each day. Between ECMO Days
      1 and 6, there was a small but significant increase in EE from 40 to 46
      kcal/kg/day (P = 0.03). In comparison, the caloric intake significantly increased
      by twice as much as EE from 30 to 61 kcal/kg/day (P = 0.017). As a result, RQ
      significantly increased from 0.6 to 1.0 (P < 0.0001). Protein intake
      significantly increased during ECMO Days 1 to 6 from 0.5 to 1.5 g/kg/day (P =
      0.04). Respiratory mass spectrometry is feasible to provide a unique and safe
      technique to measure EE and RQ in patients on ECMO. Without this knowledge,
      inadequate feeding may occur. Further studies are warranted in a larger patient
      population to provide better information to guide clinical practice in this
      special group of critically ill children. 

PMID- 25940696
TI  - Longitudinal evaluation of sexual function in a cohort of pre- and postmenopausal
      women.
AB  - INTRODUCTION: Aspects of women's sexual functioning that have received relatively
      little attention are its stability and how changes in the different sexual
      response domains influence each other over time. AIM: The aim of this study was
      to describe the changes and to evaluate the stability of self-reported sexual
      functioning over a 4-year period in a population sample of British women.
      METHODS: A 4-year follow-up study on N = 507 women, including 178 pre- and 329
      postmenopausal women, was conducted. The validated Female Sexual Function Index
      (FSFI) was applied. MAIN OUTCOME MEASURE: A multigroup path analytical model was
      used to examine autoregressive effects (the effect of a domain on itself at a
      later point in time) and cross-lag effects (one variable affecting another
      variable at a later point in time) across all FSFI domains of sexual functioning
      between pre- and postmenopausal women. RESULTS: Overall, the proportion of
      postmenopausal women suffering from a sexual dysfunction at measurement point 1
      (T1) was higher compared with premenopausal women (pre: 34.3% vs. post: 14.5%).
      However, both groups showed a comparable number of women developing a sexual
      problem (pre: 22.2% vs. post: 23.2%) or improving their sexual functioning (7.4%
      vs. 7.6%) after the 4 years. Furthermore, path model analyses revealed that each
      domain at T1 significantly predicted its level 4 years later (betas ranging from
      0.33 for arousal to 0.57 for lubrication), with the exception of sexual
      satisfaction. In terms of cross-lag effects, the changes in all domains except
      for pain were predicted either by levels of desire, arousal, or orgasm at T1
      (betas ranging from 0.18 to 0.36) in both groups. CONCLUSIONS: Women's sexual
      functioning was moderately stable across the 4 years. The main predictors of
      changes in sexual functioning and satisfaction were desire and arousal,
      highlighting their role as possible key players in women's sexual health.

PMID- 25940698
TI  - Liver polyploidy: Dr Jekyll or Mr Hide?

PMID- 25940699
TI  - The biology and treatment of oligometastatic cancer.
AB  - Clinical reports of limited and treatable cancer metastases, a disease state that
      exists in a transitional zone between localized and widespread systemic disease,
      were noted on occasion historically and are now termed oligometastasis. The
      ramification of a diagnosis of oligometastasis is a change in treatment paradigm,
      i.e. if the primary cancer site (if still present) is controlled, or resected,
      and the metastatic sites are ablated (surgically or with radiation), a prolonged
      disease-free interval, and perhaps even cure, may be achieved. Contemporary
      molecular diagnostics are edging closer to being able to determine where an
      individual metastatic deposit is within the continuum of malignancy. Preclinical
      models are on the outset of laying the groundwork for understanding the
      oligometastatic state. Meanwhile, in the clinic, patients are increasingly being
      designated as having oligometastatic disease and being treated owing to improved
      diagnostic imaging, novel treatment options with the potential to provide either
      direct or bridging therapy, and progressively broad definitions of
      oligometastasis. 

PMID- 25940701
TI  - DACH1 is a novel predictive and prognostic biomarker in hepatocellular carcinoma
      as a negative regulator of Wnt/beta-catenin signaling.
AB  - The cell fate determination factor Dachshund (DACH1) functions as a novel
      suppressor in the progression of various neoplasms. Previous study has suggested
      that hypermethylation of promoter region was responsible for the reduction of
      DACH1 expression in hepatocellular carcinoma (HCC), and associated with the
      progression of HCC, but the clinical significance and the exact molecular
      mechanisms of DACH1 in the progression of HCC remain unclear. In this study, we
      employed public microarray data analysis and tissue microarrays (TMAs)
      technologies and showed that DACH1 expression was reduced in HCC even at early
      stage and associated with the tumor progression. Notably, Kaplan-Meier analysis
      further indicated DACH1 could be an independent prognostic factor for the overall
      survival of HCC. Further, mechanistic studies revealed that overexpression of
      DACH1 inhibited the growth and migration of HCC cell line, which were dependent
      in part on the inactivation of Wnt pathway via phosphorylation of GSK3beta to
      suppress beta-catenin. In agreement, the abundance of DACH1 was inversely
      correlated with several Wnt target genes. Collectively, our study indicated beta
      catenin is a novel target of DACH1 in HCC. 

PMID- 25940702
TI  - Novel harmine derivatives for tumor targeted therapy.
AB  - Harmine is a beta-carboline alkaloid found in medicinal plant PeganumHarmala,
      which has served as a folk anticancer medicine. However, clinical applications of
      harmine were limited by its low pharmacological effects and noticeable
      neurotoxicity. In this study, we modified harmine to increase the therapeutic
      efficacy and to decrease the systemic toxicity. Specifically, two tumor targeting
      harmine derivatives 2DG-Har-01 and MET-Har-02 were synthesized by modifying
      substituent in position-2, -7 and -9 of harmine ring with two different targeting
      group2-amino-2-deoxy-D-glucose (2DG) and Methionine (Met), respectively. Their
      therapeutic efficacy and toxicity were investigated both in vitro and in vivo.
      Results suggested that the two new harmine derivatives displayed much higher
      therapeutic effects than non-modified harmine. In particular, MET-Har-02 was more
      potent than 2DG-Har-01 with promising potential for targeted cancer therapy.

PMID- 25940700
TI  - Kinase-independent role of cyclin D1 in chromosomal instability and mammary
      tumorigenesis.
AB  - Cyclin D1 is an important molecular driver of human breast cancer but better
      understanding of its oncogenic mechanisms is needed, especially to enhance
      efforts in targeted therapeutics. Currently, pharmaceutical initiatives to
      inhibit cyclin D1 are focused on the catalytic component since the transforming
      capacity is thought to reside in the cyclin D1/CDK activity. We initiated the
      following study to directly test the oncogenic potential of catalytically
      inactive cyclin D1 in an in vivo mouse model that is relevant to breast cancer.
      Herein, transduction of cyclin D1(-/-) mouse embryonic fibroblasts (MEFs) with
      the kinase dead KE mutant of cyclin D1 led to aneuploidy, abnormalities in
      mitotic spindle formation, autosome amplification, and chromosomal instability
      (CIN) by gene expression profiling. Acute transgenic expression of either cyclin
      D1(WT) or cyclin D1(KE) in the mammary gland was sufficient to induce a high CIN
      score within 7 days. Sustained expression of cyclin D1(KE) induced mammary
      adenocarcinoma with similar kinetics to that of the wild-type cyclin D1. ChIP-Seq
      studies demonstrated recruitment of cyclin D1(WT) and cyclin D1(KE) to the genes
      governing CIN. We conclude that the CDK-activating function of cyclin D1 is not
      necessary to induce either chromosomal instability or mammary tumorigenesis.

PMID- 25940703
TI  - Cell type of origin as well as genetic alterations contribute to breast cancer
      phenotypes.
AB  - Breast cancer is classified into different subtypes that are associated with
      different patient survival outcomes, underscoring the importance of understanding
      the role of precursor cell and genetic alterations in determining tumor subtypes.
      In this study, we evaluated the oncogenic phenotype of two distinct mammary
      stem/progenitor cell types designated as K5+/K19- or K5+/K19+ upon introduction
      of identical combinations of oncogenes-mutant H-Ras (mRas) and mutant p53 (mp53),
      together with either wild-type ErbB2(wtErbB2) or wild-type EGFR (wtEGFR). We
      examined their tumor forming and metastasis potential, using both in-vitro and in
      vivo assays. Both the combinations efficiently transformed K5+/K19- or K5+/K19+
      cells. Xenograft tumors formed by these cells were histologically heterogeneous,
      with variable proportions of luminal, basal-like and claudin-low type components
      depending on the cell types and oncogene combinations. Notably, K5+/K19- cells
      transformed with mRas/mp53/wtEGFR combination had a significantly longer latency
      for primary tumor development than other cell lines but more lung metastasis
      incidence than same cells expressing mRas/mp53/wtErbB2. K5+/K19+ cells exhibit
      shorter overall tumor latency, and high metastatic potential than K5+/K19- cells,
      suggesting that these K19+ progenitors are more susceptible to oncogenesis and
      metastasis. Our results suggest that both genetic alterations and cell type of
      origin contribute to oncogenic phenotype of breast tumors. 

PMID- 25940704
TI  - The cAMP responsive element binding protein 1 transactivates epithelial membrane
      protein 2, a potential tumor suppressor in the urinary bladder urothelial
      carcinoma.
AB  - In this study, we report that EMP2 plays a tumor suppressor role by inducing G2/M
      cell cycle arrest, suppressing cell viability, proliferation, colony
      formation/anchorage-independent cell growth via regulation of G2/M checkpoints in
      distinct urinary bladder urothelial carcinoma (UBUC)-derived cell lines.
      Genistein treatment or exogenous expression of the cAMP responsive element
      binding protein 1 (CREB1) gene in different UBUC-derived cell lines induced EMP2
      transcription and subsequent translation. Mutagenesis on either or both cAMP
      responsive element(s) dramatically decreased the EMP2 promoter activity with,
      without genistein treatment or exogenous CREB1 expression, respectively.
      Significantly correlation between the EMP2 immunointensity and primary tumor,
      nodal status, histological grade, vascular invasion and mitotic activity was
      identified. Multivariate analysis further demonstrated that low EMP2
      immunoexpression is an independent prognostic factor for poor disease-specific
      survival. Genistein treatments, knockdown of EMP2 gene and double knockdown of
      CREB1 and EMP2 genes significantly inhibited tumor growth and notably
      downregulated CREB1 and EMP2 protein levels in the mice xenograft models.
      Therefore, genistein induced CREB1 transcription, translation and upregulated
      pCREB1(S133) protein level. Afterward, pCREB1(S133) transactivated the tumor
      suppressor gene, EMP2, in vitro and in vivo. Our study identified a novel
      transcriptional target, which plays a tumor suppressor role, of CREB1. 

PMID- 25940705
TI  - Transcriptional co-activator TAZ sustains proliferation and tumorigenicity of
      neuroblastoma by targeting CTGF and PDGF-beta.
AB  - Neuroblastoma is a common childhood malignant tumor originated from the neural
      crest-derived sympathetic nervous system. A crucial event in the pathogenesis of
      neuroblastoma is to promote proliferation of neuroblasts, which is closely
      related to poor survival. However, mechanisms for regulation of cell
      proliferation and tumorigenicity in neuroblastoma are not well understood. Here,
      we report that overexpression of TAZ in neuroblastoma BE(2)-C cells causes
      increases in cell proliferation, self renewal and colony formation, which was
      restored back to its original levels by knockdown of TAZ in TAZ-overexpression
      cells. Inhibition of endogenous TAZ attenuated cell proliferation, colony
      formation and tumor development in neuroblastoma SK-N-AS cell, which could be
      rescued by re-introduction of TAZ into TAZ-knockdown cells. In addition, we found
      that overexpressing TAZ-mediated induction of CTGF and PDGF-beta expression, cell
      proliferation and colony formation were inhibited by knocking down CTGF and PDGF
      beta with siRNA in TAZ-overexpressing cell. Overall, our findings suggested that
      TAZ plays an essential role in regulating cell proliferation and tumorigenesis in
      neuroblastoma cells. Thus, TAZ seems to be a novel and promising target for the
      treatment of neuroblastoma. 

PMID- 25940706
TI  - Velocity-selective magnetization-prepared non-contrast-enhanced cerebral MR
      angiography at 3 Tesla: Improved immunity to B0/B1 inhomogeneity.
AB  - PURPOSE: To develop a Fourier-transform based velocity-selective (VS) pulse train
      that offers improved robustness to B0/B1 inhomogeneity for non-contrast-enhanced
      cerebral MR angiography (MRA) at 3 Tesla (T). METHODS: VS pulse train I and II
      with different saturation bands are proposed to incorporate paired and phase
      cycled refocusing pulses. Their sensitivity to B0/B1 inhomogeneity was estimated
      through simulation and compared with a single refocused VS pulse train. The
      implementation was compared to standard time of flight (TOF) among eight healthy
      subjects. RESULTS: In contrast to single refocused VS pulse train, the simulated
      VS profiles from proposed pulse trains indicate much improved immunity to field
      inhomogeneity in the brain at 3T. Successive application of two identical VS
      pulse trains yields a better suppression of static tissue at the cost of 20 ~ 30%
      signal loss within large vessels. Average relative contrast ratios of major
      cerebral arterial segments applying both pulse train I and II with two
      preparations are 0.81 +/- 0.06 and 0.81 +/- 0.05, respectively, significantly
      higher than 0.67 +/- 0.07 of TOF-MRA. VS MRA, in particular, the pulse train II
      with the narrower saturation band, depicts more small vessels with slower flow.
      CONCLUSION: VS magnetization-prepared cerebral MRA was demonstrated among normal
      subjects on a 3T scanner.

PMID- 25940707
TI  - 17beta-Estradiol Induces Overproliferation in Adenomyotic Human Uterine Smooth
      Muscle Cells of the Junctional Zone Through Hyperactivation of the Estrogen
      Receptor-Enhanced RhoA/ROCK Signaling Pathway.
AB  - Adenomyosis (ADS) is a common estrogen-dependent gynecological disease with
      unknown etiology. Recent models favor abnormal thickening of the junctional zone
      (JZ) may be the causative factor in the development of ADS. RhoA, a small
      guanosine triphosphatase which controls multiple cellular processes, is involved
      in the control of cell proliferation. Here we demonstrate that treatment of human
      uterine smooth muscle cells (SMCs) of the JZ with 17beta-estradiol (E2) increased
      expression of RhoA and its downstream effectors (-associated coiled coil
      containing protein kinase [ROCK] 1 and ROCK2). Compared with non-ADS cells, RhoA,
      ROCK1, and ROCK2 were overexpressed and hyperactivated in ADS cells. These
      effects were suppressed in the presence of ICI 182,780, supporting an estrogen
      receptor (ER)-dependent mechanism. Hyperactivation of ER-enhanced RhoA/ROCK
      signaling was associated with overproliferation in ADS human uterine SMCs of the
      JZ. Moreover, E2-induced overproliferation was accompanied by downregulation of
      cyclin-dependent kinases inhibitors (CKIs; p21(Waf1/Cip1) and p27(Kip1)) and
      upregulation of cyclin-dependent kinases (CDKs) and cyclins (cyclin D1, cyclin
      E1, CDK2, CDK4, and CDK6). 

PMID- 25940708
TI  - Change in T2* relaxation time of Hoffa fat pad correlates with histologic change
      in a rat anterior cruciate ligament transection model.
AB  - The Hoffa fat pad (infrapatellar fat pad) is a source of post-traumatic anterior
      knee pain, and Hoffa disease is a syndrome leading to chronic inflammation of the
      fat pad. Herein, change in T2* relaxation time of the fat pad was measured in a
      rodent anterior cruciate ligament transection (ACLX) model in order to (i)
      examine the causal relationship of anterior cruciate ligament (ACL) deficiency
      and Hoffa disease and (ii) demonstrate the feasibility of using T2* as an imaging
      biomarker to monitor disease progression. Three groups of male Sprague Dawley
      rats (n = 6 each group), received either (i) no intervention; (ii) sham surgery
      at the right knee; or (iii) right ACLX. T2* relaxation time was measured and
      histology was examined in the Hoffa fat pad after surgery. At 13 and 18 weeks
      after surgery, T2* values were significantly higher in the right fat pad than the
      left (p < 0.001) and significantly higher in the ACLX group than the control and
      sham groups (p < 0.001). Histology showed fibrosis and degeneration of adipocytes
      in the right knees of the ACLX group. We conclude that ACL deficiency and Hoffa
      disease are causally related and that MRI T2* value can serve as an imaging
      biomarker of Hoffa disease progression.

PMID- 25940710
TI  - Reflections on Hope and Its Implications for End-of-Life Care.
AB  - Physicians caring for individuals with life-altering, incurable illnesses often
      have a desire to convey a sense of hope while also helping their patients prepare
      for the end of life to minimize unnecessary suffering and grief. Unfortunately,
      in the United States, most people receive more-aggressive treatments toward the
      end of life than studies would suggest that they desire. This reflects the
      challenging task of balancing optimism and realism, and how providing a false
      sense of hope for a cure for too long a time while avoiding advance care planning
      may contribute significantly to the problem. This article explores the interplay
      of hope and advance care planning, and suggests a need for excellent
      individualized communication in the setting of advanced cancer to improve end-of
      life care. 

PMID- 25940711
TI  - Sulfonic acid functionalized ionic liquids for dissolution of metal oxides and
      solvent extraction of metal ions.
AB  - New sulfonic acid functionalized ionic liquids (SAFILs) with
      bis(trifluoromethylsulfonyl)imide anions were synthesized. These ionic liquids
      are strong Bronsted acids and can solubilize metal oxides. Water-immiscible
      SAFILs were used as organic phases in solvent extraction studies. 

PMID- 25940709
TI  - Regulation of UHRF1 by microRNA-9 modulates colorectal cancer cell proliferation
      and apoptosis.
AB  - The UHRF1 protein is pivotal for DNA methylation and heterochromatin formation,
      leading to decreased expressions of tumor suppressor genes and contributing to
      tumorigenesis. However, the factors that modulate UHRF1 expression in colorectal
      cancer (CRC) remain unclear. Here we showed that, compared with corresponding
      normal tissues, UHRF1 was upregulated and microRNA-9 (miR-9) was downregulated in
      CRC tissues. The expression of UHRF1 was inversely correlated with overall
      survival rates of patients with CRC. Overexpression of miR-9 in CRC cell lines
      significantly attenuated CRC cell proliferation and promoted cell apoptosis. The
      expression of UHRF1 was markedly reduced in pre-miR-9 transfected CRC cells.
      Using luciferase reporter assay, we confirmed that miR-9 was a direct upstream
      regulator of UHRF1. Finally, analysis of miR-9 and UHRF1 levels in human CRC
      tissues revealed that expression of miR-9 was inversely correlated with UHRF1
      expression. Collectively, our results offer in vitro validation of the concept
      that miR-9 could repress the expression of UHRF1, and function as a tumor
      suppressive microRNA in CRC. It may serve as a prognostic and therapeutic marker
      for CRC. 

PMID- 25940713
TI  - Suppression of SOX7 by DNA methylation and its tumor suppressor function in acute
      myeloid leukemia.
AB  - SOX7 belongs to the SOX (Sry-related high-mobility group [HMG] box) gene family,
      a group of transcription factors containing in common a HMG box domain. Its role
      in hematologic malignancies and, in particular, acute myeloid leukemia (AML) is
      completely unknown. Here, we showed that SOX7 expression was regulated by DNA
      hypermethylation in AML but not in acute lymphoblastic leukemia or normal bone
      marrow cells. In cell lines (KG1, ML2, and K562) and in primary CD34(+) AML
      samples, SOX7 expression could be induced by the DNA demethylating agent 5-aza-2'
      deoxycytidine. Overexpression of SOX7 in K562 cells inhibited cell proliferation,
      with cell cycle delay in S/G2/M phases and reduced clonogenic activity. Apoptosis
      was unaffected. Ectopic expression of SOX7 in K562 and THP-1 cells, as well as
      primary CD33(+)CD34(+) AML cells, abrogated leukemia engraftment in xenogeneic
      transplantation. SOX7 expression inhibited the Wnt/beta-catenin pathway through
      direct protein binding to beta-catenin, and the antileukemia effects of SOX7 in
      THP-1 cells were significantly reduced by deletion of its beta-catenin binding
      site. The results provided unequivocal evidence for a novel tumor suppressor role
      of SOX7 in AML via a negative modulatory effect on the Wnt/beta-catenin pathway. 

PMID- 25940712
TI  - Tumor indoleamine 2,3-dioxygenase (IDO) inhibits CD19-CAR T cells and is
      downregulated by lymphodepleting drugs.
AB  - Although T cells expressing CD19-specific chimeric antigen receptors (CARs) are a
      promising new therapy for B-cell malignancies, objective responses are observed
      at lower frequencies in patients with lymphoma than in those with acute B-cell
      leukemia. We postulated that the tumor microenvironment suppresses CAR-expressing
      T cells (CARTs) through the activity of indoleamine 2,3-dioxygenase (IDO), an
      intracellular enzyme that converts tryptophan into metabolites that inhibit T -:
      cell activity. To investigate the effects of tumor IDO on CD19-CART therapy, we
      used a xenograft lymphoma model expressing IDO as a transgene. CD19-CARTs
      inhibited IDO-negative tumor growth but had no effect on IDO-positive tumors. An
      IDO inhibitor (1-methyl-tryptophan) restored IDO-positive tumor control.
      Moreover, tryptophan metabolites inhibited interleukin (IL)-2-, IL-7-, and IL-15
      dependent expansion of CARTs; diminished their proliferation, cytotoxicity, and
      cytokine secretion in vitro in response to CD19 recognition; and increased their
      apoptosis. Inhibition of CD19-CARTs was not mitigated by the incorporation of
      costimulatory domains, such as 4-1BB, into the CD19-CAR. Finally, we found that
      fludarabine and cyclophosphamide, frequently used before CART administration,
      downregulated IDO expression in lymphoma cells and improved the antitumor
      activity of CD19-CART in vivo. Because tumor IDO inhibits CD19-CARTs,
      antagonizing this enzyme may benefit CD19-CART therapy. 

PMID- 25940714
TI  - Haploidentical vs identical-sibling transplant for AML in remission: a
      multicenter, prospective study.
AB  - The effects of HLA-identical sibling donor (ISD) hematopoietic stem cell
      transplantation (HSCT) on adults with intermediate- or high-risk acute myeloid
      leukemia (AML) in the first complete remission (CR1) are well established.
      Previous single-center studies have demonstrated similar survival after
      unmanipulated haploidentical donor (HID) vs ISD HSCT for hematologic
      malignancies. To test the hypothesis that haploidentical HSCT would be a valid
      option as postremission therapy for AML patients in CR1 lacking a matched donor,
      we designed a disease-specific, prospective, multicenter study. Between July 2010
      and November 2013, 450 patients were assigned to undergo HID (231 patients) or
      ISD HSCT (219 patients) according to donor availability. Among HID and ISD
      recipients, the 3-year disease-free survival rate was 74% and 78% (P = .34),
      respectively; the overall survival rate was 79% and 82% (P = .36), respectively;
      cumulative incidences of relapse were 15% and 15% (P = .98); and those of the
      nonrelapse-mortality were 13% and 8% (P = .13), respectively. In conclusion,
      unmanipulated haploidentical HSCT achieves outcomes similar to those of ISD HSCT
      for AML patients in CR1. Such transplantation was demonstrated to be a valid
      alternative as postremission treatment of intermediate- or high-risk AML patients
      in CR1 lacking an identical donor. This trial was registered at www.chictr.org as
      #ChiCTR-OCH-10000940. 

PMID- 25940715
TI  - Long-Term Follow-Up of a Community Assignment, One-Time Endoscopic Screening
      Study of Esophageal Cancer in China.
AB  - PURPOSE: There are no global screening recommendations for esophageal squamous
      cell carcinoma (ESCC). Endoscopic screening has been investigated in areas of
      high incidence in China since the 1970s. This study aimed to evaluate whether an
      endoscopic screening and intervention program could reduce mortality caused by
      ESCC. METHODS: Residents age 40 to 69 years were recruited from communities with
      high rates of ESCC. Fourteen villages were selected as the intervention
      communities. Ten villages not geographically adjacent to intervention villages
      were selected for comparison. Participants in the intervention group were
      screened once by endoscopy with Lugol's iodine staining, and those with dysplasia
      or occult cancer were treated. All intervention participants and a sample
      consisting of one tenth of the control group completed questionnaires. We
      compared cumulative ESCC incidence and mortality between the two groups. RESULTS:
      Three thousand three hundred nineteen volunteers (48.62%) from an eligible
      population of 6,827 were screened in the intervention group. Seven hundred ninety
      seven volunteers from an eligible population of 6,200 in the control group were
      interviewed. Six hundred fifty-two incident and 542 fatal ESCCs were identified
      during the 10-year follow-up. A reduction in cumulative mortality in the
      intervention group versus the control group was apparent (3.35% v 5.05%,
      respectively; P < .001). Furthermore, the intervention group had a significantly
      lower cumulative incidence of ESCC versus the control group (4.17% v 5.92%,
      respectively; P < .001). CONCLUSION: We showed that endoscopic screening and
      intervention significantly reduced mortality caused by esophageal cancer.
      Detection and treatment of preneoplastic lesions also led to a reduction in the
      incidence of this highly fatal cancer.

PMID- 25940716
TI  - Revised International Pediatric Non-Hodgkin Lymphoma Staging System.
AB  - PURPOSE: Treatment and prognosis of pediatric non-Hodgkin lymphoma (NHL) have
      improved dramatically in the last 30 years. However, the St Jude NHL staging
      classification for pediatric NHL was developed more than 35 years ago. The most
      recent Lugano lymphoma staging classification focused on adult lymphoma.
      Furthermore, major limitations of the current pediatric NHL staging
      classification include lack of consideration of new distinct pediatric NHL
      histologic entities; absence of recognition of frequent skin, bone, kidney,
      ovarian, and other organ involvement; and lack of newer precise methods to detect
      bone marrow and CNS involvement, minimal disease quantification, and highly
      sensitive imaging technologies. METHODS: An international multidisciplinary
      expert panel convened in Frankfurt, Germany, in 2009 at the Third International
      Childhood, Adolescent and Young Adult NHL Symposium to develop a revised
      international pediatric NHL staging system (IPNHLSS), addressing limitations of
      the current pediatric NHL staging system and creating a revised classification.
      Evidence-based disease distribution and behavior were reviewed from multiple
      pediatric cooperative group NHL studies. RESULTS: A revised IPNHLSS was developed
      incorporating new histologic entities, extranodal dissemination, improved
      diagnostic methods, and advanced imaging technology. CONCLUSION: This revised
      IPNHLSS will facilitate more precise staging for children and adolescents with
      NHL and facilitate comparisons of efficacy across different treatment strategies,
      various institutions, multicenter trials, and cooperative groups by allowing for
      reproducible pediatric-based staging at diagnosis and relapse.

PMID- 25940717
TI  - Germline BRCA Mutations in a Large Clinic-Based Cohort of Patients With
      Pancreatic Adenocarcinoma.
AB  - PURPOSE: The main purpose of this study was to determine the prevalence of
      pathogenic BRCA1 and BRCA2 mutations in a consecutively ascertained clinic-based
      cohort of patients with pancreatic ductal adenocarcinoma and describe the
      clinical and family history characteristics. PATIENTS AND METHODS: Unselected,
      consecutive, incident patients with pancreatic ductal adenocarcinoma were
      recruited at a single cancer center over a 2-year period. Participants provided
      blood for DNA analysis and cancer family history, and cancer treatment records
      were reviewed. DNA from all patients was analyzed by Sanger sequencing and
      multiplex ligation-dependent probe amplification for germline variants in BRCA1
      and BRCA2. RESULTS: Three hundred six patients were eligible for analysis.
      Pathogenic germline BRCA mutations were identified in 14 patients (4.6%; 95% CI,
      2.2% to 6.9%), including 11 patients with a BRCA2 mutation and three patients
      with a BRCA1 mutation. Having a cancer family history that met genetic testing
      criteria of the National Comprehensive Cancer Network or the Ontario Ministry of
      Health and Long-Term Care or self-reporting as Ashkenazi Jewish was significantly
      associated with BRCA mutation carrier status (P=.02, P<.001, and P=.05,
      respectively). However, the majority of the BRCA mutation-positive patients did
      not actually meet these genetic testing criteria. CONCLUSION: Pathogenic BRCA
      mutations were identified in 4.6% of a large cohort of clinic-based patients.
      Considering the implications for family members of BRCA carriers, and possibly
      tailored chemotherapeutic treatment of patients, our finding has implications for
      broader BRCA genetic testing for patients with pancreatic ductal adenocarcinoma.

PMID- 25940719
TI  - Adjuvant Chemotherapy for Locally Advanced Rectal Cancer: Is It a Given?

PMID- 25940720
TI  - Diabetes Associated With Short Survival in Pancreatic Cancer.

PMID- 25940718
TI  - Next-Generation Sequencing Panels for the Diagnosis of Colorectal Cancer and
      Polyposis Syndromes: A Cost-Effectiveness Analysis.
AB  - PURPOSE: To evaluate the cost effectiveness of next-generation sequencing (NGS)
      panels for the diagnosis of colorectal cancer and polyposis (CRCP) syndromes in
      patients referred to cancer genetics clinics. PATIENTS AND METHODS: We developed
      a decision model to evaluate NGS panel testing compared with current standard of
      care in patients referred to a cancer genetics clinic. We obtained data on the
      prevalence of genetic variants from a large academic laboratory and calculated
      the costs and health benefits of identifying relatives with a pathogenic variant,
      in life-years and quality-adjusted life-years (QALYs). We classified the CRCP
      syndromes according to their type of inheritance and penetrance of colorectal
      cancer. One-way and probabilistic sensitivity analyses were conducted to assess
      uncertainty. RESULTS: Evaluation with an NGS panel that included Lynch syndrome
      genes and other genes associated with highly penetrant CRCP syndromes led to an
      average increase of 0.151 year of life, 0.128 QALY, and $4,650 per patient,
      resulting in an incremental cost-effectiveness ratio of $36,500 per QALY compared
      with standard care and a 99% probability that this panel was cost effective at a
      threshold of $100,000 per QALY. When compared with this panel, the addition of
      genes with low colorectal cancer penetrance resulted in an incremental cost
      effectiveness ratio of $77,300 per QALY. CONCLUSION: The use of an NGS panel that
      includes genes associated with highly penetrant CRCP syndromes in addition to
      Lynch syndrome genes as a first-line test is likely to provide meaningful
      clinical benefits in a cost-effective manner at a $100,000 per QALY threshold.

PMID- 25940721
TI  - Scientific Review of Phase I Protocols With Novel Dose-Escalation Designs: How
      Much Information Is Needed?

PMID- 25940722
TI  - The Power of the Placebo in Symptom Management.

PMID- 25940723
TI  - Reply to Y. Mao et al.

PMID- 25940726
TI  - Black/White Disparities in Receipt of Treatment and Survival Among Men With Early
      Stage Breast Cancer.
AB  - PURPOSE: To examine the extent of black/white disparities in receipt of treatment
      and survival for early-stage breast cancer in men age 18 to 64 and >= 65 years.
      PATIENTS AND METHODS: We identified 725 non-Hispanic black (black) and 5,247 non
      Hispanic white (white) men diagnosed with early-stage breast cancer from 2004 to
      2011 in the National Cancer Data Base. We used multivariable logistic regression
      and calculated standardized risk ratios to predict receipt of treatment and a
      proportional hazards model to estimate overall hazard ratios (HRs) in black
      versus white men age 18 to 64 and >= 65 years, separately. RESULTS: Receipt of
      treatment was remarkably similar between blacks and whites in both age groups.
      Black and white older men had lower receipt of chemotherapy (39.2% and 42.0%,
      respectively) compared with younger patients (76.7% and 79.3%, respectively).
      Younger black men had a 76% higher risk of death than younger white men after
      adjustment for clinical factors only (HR, 1.76; 95% CI, 1.11 to 2.78), but this
      difference significantly diminished after subsequent adjustment for insurance and
      income (HR, 1.37; 95% CI, 0.83 to 2.24). In those age >= 65 years, the excess
      risk of death in blacks versus whites was nonsignificant and not affected by
      adjustment for covariates. CONCLUSION: The excess risk of death in black versus
      white men diagnosed with early-stage breast cancer was largely confined to those
      age 18 to 64 years and became nonsignificant after adjustment for differences in
      insurance and income. These findings suggest the importance of improving access
      to care in reducing racial disparities in male breast cancer mortality.

PMID- 25940725
TI  - International Pediatric Non-Hodgkin Lymphoma Response Criteria.
AB  - PURPOSE: Response criteria are well established for adult patients with non
      Hodgkin lymphoma (NHL). A revised set of response criteria in adults with NHL was
      recently published. However, NHL in children and adolescents involves different
      histologies, primary sites of disease, patterns of metastatic spread, approaches
      to therapy, and responses to treatment compared with adult NHL. However, there
      are no standardized response criteria specific to pediatric NHL. Therefore, we
      developed international standardized methods for assessing response to therapy in
      children and adolescents with NHL. METHODS: An international multidisciplinary
      group of pediatric oncologists, pathologists, biologists, and radiologists
      convened during and after the Third and Fourth International Childhood,
      Adolescent and Young Adult NHL Symposia to review existing response and outcome
      data, develop methods for response evaluation that reflect incorporation of more
      sensitive technologies currently in use, and incorporate primary and metastatic
      sites of disease for the evaluation of therapeutic response in children and
      adolescents with NHL. RESULTS: Using the current adult NHL response criteria as a
      starting point, international pediatric NHL response criteria were developed
      incorporating both contemporary diagnostic imaging and pathology techniques,
      including novel molecular and flow cytometric technologies used for the
      determination of minimal residual disease. CONCLUSION: Use of the international
      pediatric NHL response criteria in children and adolescents receiving therapy for
      NHL incorporates data obtained from new and more sensitive technologies that are
      now being widely used for disease evaluation, providing a standardized means for
      reporting treatment response.

PMID- 25940727
TI  - Axillary Osmidrosis Treatment Using an Aggressive Suction-Curettage Technique: A
      Clinical Study on Paired Control.
AB  - BACKGROUND: Axillary osmidrosis results in social and psychological problems.
      Liposuction-assisted techniques used as treatments have been reported to have
      high recurrence rates. This study aims at introducing the aggressive suction
      curettage technique in comparison to the open excision procedure. METHODS: From
      February 2009 to February 2014, 130 patients were randomly divided into two
      groups (experimental and control groups). The experimental group was treated with
      aggressive suction-curettage, while the control group was treated with an open
      excision. Postoperative assessment (skin necrosis, hematoma, scars and malodour
      recurrence) and patient satisfaction were surveyed and analyzed. RESULTS: A lower
      necrosis rate was observed in patients who received aggressive suction-curettage
      (1.88 %, p < 0.01), higher patient satisfaction (33.85 %, p < 0.01), higher
      recurrence rate (11.54 %, p < 0.05), and less ugly scars (0.77 %, p < 0.01),
      compared to those who had the open excision procedure. CONCLUSIONS: The
      aggressive suction-curettage technique appears to be a reliable treatment option
      for axillary osmidrosis.

PMID- 25940728
TI  - Reconstruction of Corner of Mouth for Elder Facial Paralysis by Suspension
      Nasolabial Fold Dermal Tissue Flap: A Modified Method.
AB  - A modified method based on existing static facial sling techniques to reconstruct
      the corner of mouth for elder facial palsy was developed and reported. According
      to the anatomy and function of the zygomatic minor and zygomatic major, this
      technique uses nasolabial dermis as a whole to attach to the orbicularis oris to
      provide attachment to the whole area. Therefore, in our method, the function of
      the zygomaticus minor and zygomaticus major were reconstructed by attaching to
      the zygomatic arch periosteum through such slings. This procedure is effective in
      improving facial symmetry and obtaining inconspicuous scarring. We believe that
      our technique is a simple, effective and reliable option for elder facial
      paralysis.

PMID- 25940724
TI  - Randomized Multicenter Placebo-Controlled Trial of Omega-3 Fatty Acids for the
      Control of Aromatase Inhibitor-Induced Musculoskeletal Pain: SWOG S0927.
AB  - PURPOSE: Musculoskeletal symptoms are the most common adverse effects of
      aromatase inhibitors (AIs) and can result in decreased quality of life and
      discontinuation of therapy. Omega-3 fatty acids (O3-FAs) can be effective in
      decreasing arthralgia resulting from rheumatologic conditions and reducing serum
      triglycerides. PATIENTS AND METHODS: Women with early-stage breast cancer
      receiving an AI who had a worst joint pain/stiffness score >= 5 of 10 using the
      Brief Pain Inventory-Short Form (BPI-SF) were randomly assigned to receive either
      O3-FAs 3.3 g or placebo (soybean/corn oil) daily for 24 weeks. Clinically
      significant change was defined as >= 2-point drop from baseline. Patients also
      completed quality-of-life (Functional Assessment of Cancer Therapy-Endocrine
      Symptoms) and additional pain/stiffness assessments at baseline and weeks 6, 12,
      and 24. Serial fasting blood was collected for lipid analysis. RESULTS: Among 262
      patients registered, 249 were evaluable, with 122 women in the O3-FA arm and 127
      in the placebo arm. Compared with baseline, the mean observed BPI-SF score
      decreased by 1.74 points at 12 weeks and 2.22 points at 24 weeks with O3-FAs and
      by 1.49 and 1.81 points, respectively, with placebo. In a linear regression
      adjusting for the baseline score, osteoarthritis, and taxane use, adjusted 12
      week BPI-SF scores did not differ by arm (P = .58). Triglyceride levels decreased
      in patients receiving O3-FA treatment and remained the same for those receiving
      placebo (P = .01). No between-group differences were seen for HDL, LDL, or C
      reactive protein. CONCLUSION: We found a substantial (> 50%) and sustained
      improvement in AI arthralgia for both O3-FAs and placebo but found no meaningful
      difference between the groups.

PMID- 25940729
TI  - The Variation with Age of 67 Macro- and Microelement Contents in Nonhyperplastic
      Prostate Glands of Adult and Elderly Males Investigated by Nuclear Analytical and
      Related Methods.
AB  - To clarify age-related changes of 67 macro- and microelement contents in prostate
      gland of adult and geriatric males, a quantitative measurement by five analytical
      methods was performed. The nonhyperplastic prostate glands of 65 subjects
      (European-Caucasian aged 21-87 years) were investigated by energy dispersive X
      ray fluorescence (EDXRF), instrumental neutron activation analysis with high
      resolution spectrometry of short-lived radionuclides (INAA-SLR), instrumental
      neutron activation analysis with high resolution spectrometry of long-lived
      radionuclides (INAA-LLR), inductively coupled plasma atomic emission spectrometry
      (ICP-AES), and inductively coupled plasma mass spectrometry (ICP-MS). The
      prostates were obtained at autopsy from subjects who died from acute illness
      (cardiac insufficiency, stroke, embolism of pulmonary artery, alcohol poisoning)
      and trauma. None of the subjects had any symptoms of prostatic disease, and all
      prostates were classified as histologically normal. The combination of nuclear
      (EDXRF, INAA-SLR, and INAA-LLR) and inductively coupled plasma (ICP-AES and ICP
      MS) analytical methods allowed estimation of the contents of 67 chemical elements
      and precisely determined the mass fraction of 54 elements in the tissue samples
      of nonhyperplastic adult and geriatric prostate glands. This work's results
      reveal that there is a significant increase with age of Bi, Cd, Co, Fe, Hg, Pb,
      Sc, Sn, Th, U, and Zn mass fractions in the prostate tissue of healthy
      individuals of ages from 21 to 60 years, as well as an increase in Ba from age 61
      up to 87 years. It implies that an age-related increase and excess in Ba, Bi, Cd,
      Co, Fe, Hg, Pb, Sc, Sn, Th, U, and Zn mass fraction in prostatic tissue may be
      one of the main factors in the etiology of benign prostatic hyperplasia (BPH) and
      prostate carcinoma (PCa). 

PMID- 25940730
TI  - The Co-induced Effects of Molybdenum and Cadmium on Antioxidants and Heat Shock
      Proteins in Duck Kidneys.
AB  - Molybdenum (Mo) is an essential element for human beings and animals; however,
      high dietary intake of Mo can lead to adverse reactions. Cadmium (Cd) is harmful
      to health. To investigate the toxicity of Mo combined with Cd in duck kidneys,
      240 ducks were randomly divided into six groups and treated with a commercial
      diet containing Mo, Cd or Mo combined with Cd. Kidneys were collected on days 30,
      60, 90 and 120 for determining the expression of heat shock proteins (HSPs),
      including HSP60, HSP70 and HSP90 in the kidney through quantitative RT-PCR. We
      also determined the antioxidant activity indexes in the kidney mitochondria.
      Moreover, kidney tissues at 120 days were subjected to histopathological analysis
      with the optical microscope. The results indicated that the expression of HSPs
      was highly significantly (P < 0.01) upregulated in the kidneys of the combination
      groups and the Cd group. Exposure to Cd and a high dose of Mo decreased the total
      antioxidative capacity and the activity of xanthine oxidase, while
      malondialdehyde levels and the activity of nitric oxide synthase increased
      compared with those of the control groups in the kidney mitochondria. This was
      particularly evident at 90 and 120 days. Histopathological lesions included
      congestion and bleeding in the renal interstitium, swelling of the distal
      convoluted tubule epithelial cells, granular degeneration and blister
      degeneration in the renal tubular epithelial cells. These results suggest that a
      combination of Mo and Cd leads to greater tissue damage and has a synergistic
      effect on kidney damage. Oxidative damage of kidney mitochondria may be a
      potential nephrotoxicity mechanism of molybdenum and cadmium, and the high
      expression of HSPs may play a role in the resistance of kidney toxicity induced
      by Mo and Cd. 

PMID- 25940731
TI  - Decoding the conformation-linked functional properties of nucleic acids by the
      use of computational tools.
AB  - DNA and RNA are large and flexible polymers selected by nature to transmit
      information. The most common DNA three-dimensional structure is represented by
      the double helix, but this biopolymer is extremely flexible and polymorphic, and
      can easily change its conformation to adapt to different interactions and
      purposes. DNA can also adopt singular topologies, giving rise, for instance, to
      supercoils, formed because of the limited free rotation of the DNA domain
      flanking a replication or transcription complex. Our understanding of the
      importance of these unusual or transient structures is growing, as recent studies
      of DNA topology, supercoiling, knotting and linking have shown that the geometric
      changes can drive, or strongly influence, the interactions between protein and
      DNA, so altering its own metabolism. On the other hand, the unique self
      recognition properties of DNA, determined by the strict Watson-Crick rules of
      base pairing, make this material ideal for the creation of self-assembling,
      predesigned nanostructures. The construction of such structures is one of the
      main focuses of the thriving area of DNA nanotechnology, where several assembly
      strategies have been employed to build increasingly complex DNA nanostructures.
      DNA nanodevices can have direct applications in biomedicine, but also in the
      materials science field, requiring the immersion of DNA in an environment far
      from the physiological one. Crucial help in the understanding and planning of
      natural and artificial nanostructures is given by modern computer simulation
      techniques, which are able to provide a reliable structural and dynamic
      description of nucleic acids. 

PMID- 25940732
TI  - Analysis of the intricate relationship between chronic inflammation and cancer.
AB  - Deregulated inflammatory response plays a pivotal role in the initiation,
      development and progression of tumours. Potential molecular mechanism(s) that
      drive the establishment of an inflammatory-tumour microenvironment is not
      entirely understood owing to the complex cross-talk between pro-inflammatory and
      tumorigenic mediators such as cytokines, chemokines, oncogenes, enzymes,
      transcription factors and immune cells. These molecular mediators are critical
      linchpins between inflammation and cancer, and their activation and/or
      deactivation are influenced by both extrinsic (i.e. environmental and lifestyle)
      and intrinsic (i.e. hereditary) factors. At present, the research pertaining to
      inflammation-associated cancers is accumulating at an exponential rate. Interest
      stems from hope that new therapeutic strategies against molecular mediators can
      be identified to assist in cancer treatment and patient management. The present
      review outlines the various molecular and cellular inflammatory mediators
      responsible for tumour initiation, progression and development, and discusses the
      critical role of chronic inflammation in tumorigenesis.

PMID- 25940733
TI  - Pseudoproteases: mechanisms and function.
AB  - Catalytically inactive enzymes (also known as pseudoproteases, protease
      homologues or paralogues, non-peptidase homologues, non-enzymes and
      pseudoenzymes) have traditionally been hypothesized to act as regulators of their
      active homologues. However, those that have been characterized demonstrate that
      inactive enzymes have an extensive and expanding role in biological processes,
      including regulation, inhibition and immune modulation. With the emergence of
      each new genome, more inactive enzymes are being identified, and their abundance
      and potential as therapeutic targets has been realized. In the light of the
      growing interest in this emerging field the present review focuses on the
      classification, structure, function and mechanism of inactive enzymes. Examples
      of how inactivity is defined, how this is reflected in the structure, functions
      of inactive enzymes in biological processes and their mode of action are
      discussed.

PMID- 25940735
TI  - A Web site-based reporting system for monitoring home treatment during oral
      immunotherapy for food allergy.
AB  - BACKGROUND: Reactions during the home treatment phase of oral immunotherapy (OIT)
      are not uncommon. An ongoing accurate reporting of home treatment outcomes is
      crucial for the safety and success of OIT. Previous reports have shown that as
      few as 20% of patients are truly compliant with paper-based diaries. OBJECTIVE:
      To develop a Web site-based electronic reporting system (web-RS) for monitoring
      home treatment during OIT for food allergy. METHODS: A web-RS was developed and
      incorporated a thorough questionnaire querying for pertinent data including the
      dose(s) consumed, occurrence and details of adverse reactions, treatment(s), and
      relevant potential exacerbating factors. All patients enrolled in milk, peanut,
      or egg OIT programs for at least 4 weeks from November 2012 through January 2014
      were introduced to web-RS (n = 157). Successful reporting through web-RS was
      defined by consecutive reporting during the first home treatment phase (24 days)
      after its introduction. Comparisons were made with a previous group of OIT
      treated patients (n = 100) who reported by E-mail. RESULTS: Successful reporting
      was achieved by 142 of 157 patients (90.44%) in contrast to a 75% success rate
      with E-mail (P = .0009). The odds for successful reporting using web-RS were 3.1
      (95% confidence interval 1.6-6.3) times higher compared with using E-mail. Mild
      reactions were reported more frequently with web-RS (P = .0032). Patient reports
      were constantly available in real time for medical staff review. No complaints
      regarding web-RS feasibility were reported. One risk factor for failure to use
      web-RS was a patient's prior successful OIT experience without using web-RS (P =
      .012). CONCLUSION: A web-RS can be a powerful tool for improving OIT safety by
      achieving a high level of patient cooperation in reporting home treatment
      results.

PMID- 25940734
TI  - Changes of Virtual Planar QRS and T Vectors Derived from Holter in the
      Populations with and without Diabetes Mellitus.
AB  - AIMS: Research related to type 2 diabetes mellitus (DM) and parameters of
      electrocardiography (ECG) was limited. Patients with and without DM (NDM) were
      randomly enrolled in a study to exploit the influence of DM on planar QRS and T
      vectors derived from the Virtual Holter process. METHODS: A total of 216 (NDM)
      and 127 DM patients were consecutively and randomly recruited. We selected a 1
      minute length of ECG, which was scheduled for analysis at 4 AM. After a series of
      calculating algorisms, we received the virtual planar vector parameters. RESULTS:
      Patients with DM were elderly (65.61 +/- 12.08 vs 59.41 +/- 16.86 years, P <
      0.001); higher morbidity of hypertension (76.38% vs 58.14%, P < 0.001) and
      coronary artery disease (44.09% vs 32.41%, P = 0.03); thicker interventricular
      septum (10.92 +/- 1.77 vs 10.08 +/- 1.96 mm, P < 0.001) and left ventricular
      posterior wall (9.84 +/- 1.38 vs 9.39 +/- 1.66 mm, P = 0.03); higher lipid levels
      and average heart rate (66.67 +/- 12.04 vs 61.87 +/- 13.36 bpm, P < 0.01); higher
      angle of horizontal QRS vector (HQRSA, -2.87 +/- 48.48 vs -19.00 +/- 40.18
      degrees, P < 0.01); lower maximal magnitude of horizontal T vector (HTV, 2.33 +/-
      1.47 vs 2.88 +/- 1.89 mm, P = 0.01) and maximal magnitude of right side T vector
      (2.77 +/- 1.55 vs 3.27 +/- 1.92 mm, P = 0.03), and no difference in angle of
      frontal QRS-T vector (FQRSTA, 32.77 +/- 54.20 vs 28.39 +/- 52.87 degrees, P =
      0.74) compared with patients having NDM. After adjusting for confounding factors,
      DM was significantly effective on FQRSTA (regression coefficient -40.0, 95%CI 
      66.4 to -13.6, P < 0.01), HQRSA (regression coefficient 22.6, 95%CI 2.5 to 42.8,
      P = 0.03), and HTV (regression coefficient 0.9, 95%CI 0.2 to 1.7, P = 0.01).
      Confounding factors included: sex, 2-hour postprandial blood glucose, smoking,
      triglyceride, apolipoprotein A, creatinine, left ventricular ejection fraction,
      and average heart rate. CONCLUSIONS: The risk factors of DM and lipid metabolism
      abnormality particularly apolipoprotein A significantly modified parameters of
      virtual planar QRS and T vector, including frontal QRS-T angle.

PMID- 25940736
TI  - Changes in American Adults' Sexual Behavior and Attitudes, 1972-2012.
AB  - In the nationally representative General Social Survey, U.S. Adults (N = 33,380)
      in 2000-2012 (vs. the 1970s and 1980s) had more sexual partners, were more likely
      to have had sex with a casual date or pickup or an acquaintance, and were more
      accepting of most non-marital sex (premarital sex, teen sex, and same-sex sexual
      activity, but not extramarital sex). The percentage who believed premarital sex
      among adults was "not wrong at all" was 29 % in the early 1970s, 42 % in the
      1980s and 1990s, 49 % in the 2000s, and 58 % between 2010 and 2012. Mixed effects
      (hierarchical linear modeling) analyses separating time period, generation/birth
      cohort, and age showed that the trend toward greater sexual permissiveness was
      primarily due to generation. Acceptance of non-marital sex rose steadily between
      the G.I. generation (born 1901-1924) and Boomers (born 1946-1964), dipped
      slightly among early Generation X'ers (born 1965-1981), and then rose so that
      Millennials (also known as Gen Y or Generation Me, born 1982-1999) were the most
      accepting of non-marital sex. Number of sexual partners increased steadily
      between the G.I.s and 1960s-born GenX'ers and then dipped among Millennials to
      return to Boomer levels. The largest changes appeared among White men, with few
      changes among Black Americans. The results were discussed in the context of
      growing cultural individualism and rejection of traditional social rules in the
      U.S.

PMID- 25940737
TI  - Commentary on Kishida and Rahman (2015), Including a Meta-analysis of Relevant
      Studies on Fraternal Birth Order and Sexual Orientation in Men.

PMID- 25940738
TI  - Ligand-Controlled CO2 Activation Mediated by Cationic Titanium Hydride Complexes,
      [LTiH](+) (L=Cp2 , O).
AB  - CO2 activation mediated by [LTiH](+) (L=Cp2 , O) is observed in the gas phase at
      room temperature using electrospray-ionization mass spectrometry, and reaction
      details are derived from traveling wave ion-mobility mass spectrometry. Wheresas
      oxygen-atom transfer prevails in the reaction of the oxide complex [OTiH](+) with
      CO2 , generating [OTi(OH)](+) under the elimination of CO, insertion of CO2 into
      the metal-hydrogen bond of the cyclopentadienyl complex, [Cp2 TiH](+) , gives
      rise to the formate complex [Cp2 Ti(O2 CH)](+) . DFT-based methods were employed
      to understand how the ligand controls the observed variation in reactivity toward
      CO2 . Insertion of CO2 into the Ti-H bond constitutes the initial step for the
      reaction of both [Cp2 TiH](+) and [OTiH](+) , thus generating formate complexes
      as intermediates. In contrast to [Cp2 Ti(O2 CH)](+) which is kinetically stable,
      facile decarbonylation of [OTi(O2 CH)](+) results in the hydroxo complex
      [OTi(OH)](+) . The longer lifetime of [Cp2 Ti(O2 CH)](+) allows for secondary
      reactions with background water, as a result of which, [Cp2 Ti(OH)](+) is formed.
      Further, computational studies reveal a good linear correlation between the
      hydride affinity of [LTi](2+) and the barrier for CO2 insertion into various
      [LTiH](+) complexes. Understanding the intrinsic ligand effects may provide
      insight into the selective activation of CO2 .

PMID- 25940739
TI  - Pediatric Lichen Sclerosus: A Review of the Epidemiology and Treatment Options.
AB  - Lichen sclerosus (LS) is a rare, chronic, inflammatory disease of the skin that
      primarily affects postmenopausal women but may occur in men and children as well.
      Approximately 7% to 15% of cases are believed to occur in children. The
      epidemiologic data for LS have been limited and treatment options are not well
      studied, particularly in children. We reviewed new developments available in the
      current literature on the epidemiology and management of LS for children.

PMID- 25940740
TI  - Pesticide analysis in toasted barley and chickpea flours.
AB  - Analytical potentiality of a modified version of the QuEChERS (Quick, Easy,
      Cheap, Effective, Rugged and Safe) method has been studied and validated for the
      extraction of a group of 11 pesticides (ethoprophos, cadusafos, dimethoate,
      terbufos, disulfoton, chlorpyrifos-methyl, fenitrothion, pirimiphos-methyl,
      malathion, chlorpyrifos and fensulfothion) and some of their metabolites
      (malaoxon, disulfoton sulfoxide, terbufos sulfone and disulfoton sulfone) in
      toasted barley and chickpea flours. The method involves separation and
      quantification by gas chromatography (GC) with nitrogen phosphorus detection
      (NPD) using triphenylphosphate as the internal standard. Matrix-matched
      calibration was carried out for both flours due to the existence of a matrix
      effect. Linearity, recovery, precision and accuracy studies of the proposed
      QuEChERS-GC-NPD method were evaluated in each sample matrix. Mean recovery values
      were in the range of 73-118% with relative standard deviation values below 10%.
      Limits of detection of the whole method were between 0.07 and 57.39 MUg/kg. The
      method was finally applied for the analysis of 14 samples collected in different
      zones of the Tenerife island. The residues of pirimiphos-methyl were found in 13
      of them, confirming its unequivocal presence by mass spectrometry. 

PMID- 25940741
TI  - Influence of material property variability on the mechanical behaviour of carotid
      atherosclerotic plaques: a 3D fluid-structure interaction analysis.
AB  - Mechanical analysis has been shown to be complementary to luminal stenosis in
      assessing atherosclerotic plaque vulnerability. However, patient-specific
      material properties are not available and the effect of material properties
      variability has not been fully quantified. Media and fibrous cap (FC) strips from
      carotid endarterectomy samples were classified into hard, intermediate and soft
      according to their incremental Young's modulus. Lipid and intraplaque
      haemorrhage/thrombus strips were classified as hard and soft. Idealised geometry
      based 3D fluid-structure interaction analyses were performed to assess the impact
      of material property variability in predicting maximum principal stress (Stress
      P1 ) and stretch (Stretch-P1 ). When FC was thick (1000 or 600 um), Stress-P1 at
      the shoulder was insensitive to changes in material stiffness, whereas Stress-P1
      at mid FC changed significantly. When FC was thin (200 or 65 um), high stress
      concentrations shifted from the shoulder region to mid FC, and Stress-P1 became
      increasingly sensitive to changes in material properties, in particular at mid
      FC. Regardless of FC thickness, Stretch-P1 at these locations was sensitive to
      changes in material properties. Variability in tissue material properties
      influences both the location and overall stress/stretch value. This variability
      needs to be accounted for when interpreting the results of mechanical modelling.

PMID- 25940742
TI  - The tyrosine gate of the bacterial lectin FimH: a conformational analysis by NMR
      spectroscopy and X-ray crystallography.
AB  - Urinary tract infections caused by uropathogenic E. coli are among the most
      prevalent infectious diseases. The mannose-specific lectin FimH mediates the
      adhesion of the bacteria to the urothelium, thus enabling host cell invasion and
      recurrent infections. An attractive alternative to antibiotic treatment is the
      development of FimH antagonists that mimic the physiological ligand. A large
      variety of candidate drugs have been developed and characterized by means of in
      vitro studies and animal models. Here we present the X-ray co-crystal structures
      of FimH with members of four antagonist classes. In three of these cases no
      structural data had previously been available. We used NMR spectroscopy to
      characterize FimH-antagonist interactions further by chemical shift perturbation.
      The analysis allowed a clear determination of the conformation of the tyrosine
      gate motif that is crucial for the interaction with aglycone moieties and was not
      obvious from X-ray structural data alone. Finally, ITC experiments provided
      insight into the thermodynamics of antagonist binding. In conjunction with the
      structural information from X-ray and NMR experiments the results provide a
      mechanism for the often-observed enthalpy-entropy compensation of FimH
      antagonists that plays a role in fine-tuning of the interaction.

PMID- 25940743
TI  - Challenging Previously Held Beliefs About Clinical Practice: Evidence or
      Experience?

PMID- 25940744
TI  - Author's Reply to Johnson and Noble.

PMID- 25940745
TI  - Chronic Pruritus: Histamine Is Not Always the Answer!

PMID- 25940746
TI  - Acknowledging the Person in the Clinical Encounter: Whole Person Care for
      Patients and Clinicians Alike. Commentary on Chochinov et al.

PMID- 25940747
TI  - Determinants of dietary supplement use--healthy individuals use dietary
      supplements.
AB  - The prevalence of dietary supplement use varies largely among populations, and
      previous studies have indicated that it is high in the Danish population compared
      with other European countries. The diversity in supplement use across countries
      indicates that cultural and environmental factors could influence the use of
      dietary supplements. Only few studies investigating the use of dietary
      supplements have been conducted in the Danish population. The present cross
      sectional study is based on 54,948 Danes, aged 50-64 years, who completed self
      administrated questionnaires on diet, dietary supplements and lifestyle between
      1993 and 1997. A health index including smoking, physical activity, alcohol and
      diet, and a metabolic risk index including waist circumference, urinary glucose
      and measured hypertension were constructed. Logistic regression was used to
      investigate these determinants in relation to the intake of dietary supplements.
      We found that 71 % of the participants were dietary supplement users; female sex,
      older age groups and higher educated participants were more likely to be users of
      any dietary supplements. One additional point in the health index was associated
      with 19, 16 and 9 % higher likelihood of being user of any, more common and less
      common supplements, respectively. In the metabolic risk index, one additional
      point was associated with 17 and 16 % lower likelihood of being user of any
      supplement and more common supplements, respectively. No significant association
      was found for less common supplement use. In conclusion, those with the
      healthiest lifestyle were more likely to use dietary supplements. Thus, lifestyle
      and dietary composition should be considered as confounders on supplement use and
      health outcomes.

PMID- 25940748
TI  - Aging Drosophila melanogaster display altered pre- and postsynaptic
      ultrastructure at adult neuromuscular junctions.
AB  - Although age-related changes in synaptic plasticity are an important focus within
      neuroscience, little is known about ultrastructural changes of synaptic
      morphology during aging. Here we report how aging affects synaptic ultrastructure
      by using fluorescence and electron microscopy at the adult Drosophila
      neuromuscular junction (NMJ) of ventral abdominal muscles. Mainly four striking
      morphological changes of aging NMJs were revealed. 1) Bouton size increases with
      proportionally rising number of active zones (AZs). 2) Synaptic vesicle density
      at AZs is increased in old flies. 3) Late endosomes, cisternae, and
      multivesicular bodies accumulate in the presynaptic terminal, and vesicles
      accumulate between membranes of the terminal bouton and the subsynaptic
      reticulum. 4) The electron-dense pre- and postsynaptic apposition is expanded in
      aging NMJs, which is accompanied by an expansion of the postsynaptic glutamate
      receptor fields. These findings suggest that aging is possibly accompanied by
      impaired synaptic vesicle release and recycling and a potentially compensatory
      expansion of AZs and postsynaptic densities.

PMID- 25940750
TI  - Sequential growth of long DNA strands with user-defined patterns for
      nanostructures and scaffolds.
AB  - DNA strands of well-defined sequence are valuable in synthetic biology and
      nanostructure assembly. Drawing inspiration from solid-phase synthesis, here we
      describe a DNA assembly method that uses time, or order of addition, as a
      parameter to define structural complexity. DNA building blocks are sequentially
      added with in-situ ligation, then enzymatic enrichment and isolation. This yields
      a monodisperse, single-stranded long product (for example, 1,000 bases) with user
      defined length and sequence pattern. The building blocks can be repeated with
      different order of addition, giving different DNA patterns. We organize DNA
      nanostructures and quantum dots using these backbones. Generally, only a small
      portion of a DNA structure needs to be addressable, while the rest is purely
      structural. Scaffolds with specifically placed unique sites in a repeating motif
      greatly minimize the number of components used, while maintaining addressability.
      This combination of symmetry and site-specific asymmetry within a DNA strand is
      easily accomplished with our method. 

PMID- 25940749
TI  - Strength training-induced responses in older adults: attenuation of descending
      neural drive with age.
AB  - Although reductions in resting H-reflex responses and maximal firing frequency
      suggest that reduced efferent drive may limit muscle strength in elderly, there
      are currently no reports of V-wave measurements in elderly, reflecting the
      magnitude of efferent output to the muscle during maximal contraction.
      Furthermore, it is uncertain whether potential age-related neural deficiencies
      can be restored by resistance training. We assessed evoked reflex recordings in
      the triceps surae muscles during rest and maximal voluntary contraction (MVC),
      rate of force development (RFD), and muscle mass in seven elderly (74 +/- 6
      years) males before and after 8 weeks of heavy resistance training, contrasted by
      seven young (24 +/- 4 years) male controls. At baseline, m. soleus (SOL) V/M
      ratio (0.124 +/- 0.082 vs. 0.465 +/- 0.197, p < 0.05) and H/M ratio (0.379 +/-
      0.044 vs. 0.486 +/- 0.101 p = 0.07) were attenuated in elderly compared to young.
      Also, SOL H-reflex latency (33.29 +/- 2.41 vs. 30.29 +/- 0.67 ms, p < 0.05) was
      longer in elderly. The reduced neural drive was, despite similar leg muscle mass
      (10.7 +/- 1.2 vs. 11.5 +/- 1.4 kg), mirrored by lower MVC (158 +/- 48 vs. 240 +/-
      54 Nm, p < 0.05) and RFD (294 +/- 126 vs. 533 +/- 123 Nm s(-1), p < 0.05) in
      elderly. In response to training SOL V/M ratio (0.184 +/- 0.092, p < 0.05)
      increased in the elderly, yet only to a level ~40 % of the young. This was
      accompanied by increased MVC (190 +/- 70 Nm, p < 0.05) and RFD (401 +/- 147
      Nm[Symbol: see text]s(-1), p < 0.05) to levels of ~80 % and ~75 % of the young.
      H/M ratio remained unchanged. These findings suggest that changes in supraspinal
      activation play a significant role in the age-related changes in muscle strength.
      Furthermore, this motor system impairment can to some extent be improved by heavy
      resistance training.

PMID- 25940751
TI  - Total synthesis of (-)-deguelin via an iterative pyran-ring formation strategy.
AB  - Enantioselective synthesis of (-)-deguelin was accomplished via an iterative
      pyran-ring formation approach. The key features involve the anionic addition of a
      chromene unit to aryloxy alkyl aldehyde for the double cyclization precursor and
      iterative pyran ring formation by Pd-catalyzed O-arylation and C-arylation,
      respectively. 

PMID- 25940752
TI  - Laboratory Evaluation of Hemolysis and Systemic Inflammatory Response in Neonatal
      Nonpulsatile and Pulsatile Extracorporeal Life Support Systems.
AB  - The objective of this study was to compare the systemic inflammatory response and
      hemolytic characteristics of a conventional roller pump (HL20-NP) and an
      alternative diagonal pump with nonpulsatile (DP3-NP) and pulsatile mode (DP3-P)
      in simulated neonatal extracorporeal life support (ECLS) systems. The
      experimental neonatal ECLS circuits consist of a conventional Jostra HL20 roller
      pump or an alternative Medos DP3 diagonal pump, and Medos Hilite 800 LT hollow
      fiber oxygenator with diffusion membrane. Eighteen sterile circuits were primed
      with freshly donated whole blood and divided into three groups: conventional HL20
      with nonpulsatile flow (HL20-NP), DP3 with nonpulsatile flow (DP3-NP), and DP3
      with pulsatile flow (DP3-P). All trials were conducted for durations of 12 h at a
      flow rate of 500 mL/min at 36 degrees C. Simultaneous blood flow and pressure
      waveforms were recorded. Blood samples were collected to measure plasma-free
      hemoglobin (PFH), human tumor necrosis factor-alpha, interleukin-6 (IL-6), and IL
      8, in addition to the routine blood gas, lactate dehydrogenase, and lactic acid
      levels. HL20-NP group had the highest PFH levels (mean +/- standard error of the
      mean) after a 12-h ECLS run, but the difference among groups did not reach
      statistical significance (HL20-NP group: 907.6 +/- 253.1 mg/L, DP3-NP group:
      343.7 +/- 163.2 mg/L, and DP3-P group: 407.6 +/- 156.6 mg/L, P = 0.06). Although
      there were similar trends but no statistical differences for the levels of
      proinflammatory cytokines among the three groups, the HL20-NP group had much
      greater levels than the other groups (P > 0.05). Pulsatile flow generated higher
      total hemodynamic energy and surplus hemodynamic energy levels at pre-oxygenator
      and pre-clamp sites (P < 0.01). Our study demonstrated that the alternative
      diagonal pump ECLS circuits appeared to have less systemic inflammatory response
      and hemolysis compared with the conventional roller pump ECLS circuit in
      simulated neonatal ECLS systems. Pulsatile flow delivered more hemodynamic energy
      to the pseudo-patient without increased odds of hemolysis compared with the
      conventional, nonpulsatile roller pump group. 

PMID- 25940753
TI  - Cellulite: an evidence-based review.
AB  - BACKGROUND: Cellulite is a multifactorial condition that is present in 80-90 % of
      post-pubertal women. Despite its high prevalence, it remains a major cosmetic
      concern for women. A wide range of products and treatments for cellulite
      reduction is available; however, no systematic review has been performed so far
      to evaluate the efficacy of the available treatment options for cellulite.
      OBJECTIVE: The objective of this review is to provide a systematic evaluation of
      the scientific evidence of the efficacy of treatments for cellulite reduction.
      METHODS: This systematic review followed the PRISMA guidelines for reporting
      systematic reviews and meta-analyses. Only original articles in English or German
      reporting data on the efficacy of cellulite treatments from in vivo human studies
      were considered. In total, 67 articles were analyzed for the following
      information: therapy, presence of a control group, randomization, blinding,
      sample size, description of statistical methods, results, and level of evidence.
      RESULTS: Most of the evaluated studies, including laser- and light-based
      modalities, radiofrequency, and others had important methodological flaws; some
      did not use cellulite severity as an endpoint or did not provide sufficient
      statistical analyses. Of the 67 studies analyzed in this review, only 19 were
      placebo-controlled studies with randomization. Some evidence for potential
      benefit was only seen for acoustic wave therapy (AWT) and the 1440 nm Nd:YAG
      minimally invasive laser. CONCLUSION: This article provides a systematic
      evaluation of the scientific evidence of the efficacy of treatment for cellulite
      reduction. No clear evidence of good efficacy could be identified in any of the
      evaluated cellulite treatments.

PMID- 25940754
TI  - Synthesis of chemicals by metabolic engineering of microbes.
AB  - Metabolic engineering is a powerful tool for the sustainable production of
      chemicals. Over the years, the exploration of microbial, animal and plant
      metabolism has generated a wealth of valuable genetic information. The prudent
      application of this knowledge on cellular metabolism and biochemistry has enabled
      the construction of novel metabolic pathways that do not exist in nature or
      enhance existing ones. The hand in hand development of computational technology,
      protein science and genetic manipulation tools has formed the basis of powerful
      emerging technologies that make the production of green chemicals and fuels a
      reality. Microbial production of chemicals is more feasible compared to plant and
      animal systems, due to simpler genetic make-up and amenable growth rates. Here,
      we summarize the recent progress in the synthesis of biofuels, value added
      chemicals, pharmaceuticals and nutraceuticals via metabolic engineering of
      microbes. 

PMID- 25940755
TI  - Impact of visceral leishmaniasis and curative chemotherapy on cytochrome P450
      activity in Brazilian patients.
AB  - AIMS: The aim of the present study was to investigate the impact of human
      visceral leishmaniasis (VL) and curative chemotherapy on the activity of
      cytochrome P450 (CYP) 3A, CYP2C9 and CYP2C19 in patients from an endemic region
      in Brazil. METHODS: Adult patients with parasitologically confirmed VL were given
      a CYP phenotyping cocktail, comprising midazolam, omeprazole and losartan,
      immediately before (Study phase 1), 2-3 days (phase 2) and 3-6 months (phase 3)
      after curative VL chemotherapy. CYP activity was assessed by the apparent
      clearance of midazolam (CYP3A), omeprazole/5-hydroxyomeprazol ratio in plasma
      (CYP2C19) and losartan/E3174 ratio in urine (CYP2C9). RESULTS: Mean values (95%
      confidence interval) in phases 1, 2 and 3 were, respectively: log apparent
      midazolam clearance, 1.21 (1.10-1.31), 1.45 (1.32-1.57) and 1.35 (1.26-1.44) ml
      min(-1)  kg(-1) ; omeprazole/5-hydroxyomeprazole ratio, 0.78 (0.61-0.94), 0.45
      (0.27-0.63) and 0.37 (0.20-0.55); losartan/E3174 ratio, 0.66 (0.39-0.92), 0.35
      (0.20-0.50) and 0.35 (0.16-0.53). Analysis of variance revealed significant
      differences in CYP3A (P = 0.018) and CYP2C19 (P = 0.008), but not CYP2C9 (P =
      0.11) phenotypic activity, across the three study phases. CONCLUSION: The
      phenotypic activities of CYP3A4 and CYP2C19 were significantly reduced during
      acute VL compared with post-chemotherapy. We propose that increased plasma
      concentrations of proinflammatory cytokines during active disease account for the
      suppression of CYP activity. The failure to detect significant changes in CYP2C9
      activity in the overall cohort may reflect differential effects of the
      inflammatory process on the expression of CYP isoforms, although the possibility
      of insufficient statistical power cannot be dismissed.

PMID- 25940756
TI  - Reconsideration about the aggressive surgery for resectable pancreatic cancer: a
      focus on real pathological portosplenomesenteric venous invasion.
AB  - BACKGROUND: Some clinicians have argued that combining pancreatic and
      portomesenteric venous resection could improve the rates of long-term survival.
      However, whether resection of the portosplenomesenteric vein could provide an
      acceptable survival benefit to patients with pancreatic cancer involving the
      portosplenomesenteric system remains controversial. The purpose of this study was
      to determine the significance of pathological portosplenomesenteric venous
      invasion on survival in patients who underwent surgical management for pancreatic
      adenocarcinoma. METHODS: Patients who underwent curative surgical treatment were
      divided into two subgroups: those with pathological invasion to the
      portosplenomesenteric vein (PV-positive group) and those without invasion (PV
      negative group). RESULTS: Of 160 studied patients, the median overall survival
      was 48.0 months after pancreatic surgery in the PV-negative group and 18.0 months
      in the PV-positive group. The incidence of postoperative peritoneal dissemination
      was significantly lower in the PV-negative group than in the PV-positive group.
      Accordingly, patients in the PV-negative group showed a cumulative rate of
      pancreatic cancer recurrence at 2 years after pancreatic surgery of 54.4%, while
      this rate was 89.4% in the PV-positive group. Finally, an elevated presurgical
      serum CA19-9 level (>700 IU/mL) was found to be significantly associated with a
      poor outcome after surgery in pancreatic cancer patients with pathological
      portosplenomesenteric venous invasion. CONCLUSIONS: Pancreatic cancer carries a
      high risk of recurrence even if surgical resection is technically possible. The
      current study suggested that portosplenomesenteric involvement and preoperative
      high serum CA19-9 are poor prognostic indications; however, the findings provided
      little insight into the role of neoadjuvant therapy in such patients.

PMID- 25940757
TI  - Phosphorylcholine antibodies are diminished in ANCA-associated vasculitis.
AB  - BACKGROUND/AIM: ANCA-associated (AAV) vasculitis is an autoimmune small-vessel
      vasculitis and may be associated with accelerated atherosclerosis as suggested by
      current literature. Antibodies against oxidized lipoproteins (OxLDL) and
      phosphorylcholine (Pc) protect from atherosclerosis. This study characterizes
      these antibodies in AAV. METHODS: Pc- and anti-OxLDL antibodies were determined
      in sera of 39 AAV patients and 44 healthy controls (HC). Intima-media thickness
      (IMT, carotids) and pulse wave velocity (PWV, A. femoralis) were measured.
      RESULTS: Pc-/OxLDL IgM antibodies were significantly reduced in AAV. IMT and PWV
      were negatively associated with anti-Pc antibodies in HC only. CONCLUSION:
      Atheroprotective anti-Pc/anti-OxLDL antibodies are significantly reduced in AAV
      possibly explaining accelerated atherosclerosis in vasculitis patients.

PMID- 25940758
TI  - Reconstruction using a divided latissimus dorsi muscle flap after conventional
      posterolateral thoracotomy and the effectiveness of indocyanine green
      fluorescence angiography to assess intraoperative blood flow.
AB  - PURPOSE: In most general thoracic operations performed via standard
      posterolateral thoracotomy, such as for descending aortic aneurysms and lung
      cancer, the latissimus dorsi (LD) muscle is divided. However, division of the LD
      can hamper reconstructive surgery because the initial operation creates unstable
      blood flow to the divided LD. We conducted this study to assess blood flow in a
      divided distal LD muscle flap using intraoperative indocyanine green-fluorescence
      angiography (ICG-FA) with the Hyper Eye Medical System((r)) (Mizuho Medical Co.,
      Ltd., Tokyo, Japan). METHODS: The subjects were 11 patients who underwent
      posterolateral thoracotomy with reconstructive surgery using a divided distal LD
      and other peripheral muscle flaps. Intraoperative ICG-FA was conducted to assess
      blood flow to the LD. RESULTS: Intraoperative ICG-FA revealed that at least two
      intercostal perforators from the sixth to the tenth intercostal spaces were
      preserved as feeding vessels to the divided distal LD. There were no major
      complications associated with inadequate blood flow to the muscle flaps.
      CONCLUSION: Intraoperative ICG-FA proved extremely useful for assessing altered
      blood flow of the divided LD and for selecting preserved intercostal perforators.

PMID- 25940759
TI  - Randomized, double-blinded, vehicle-controlled, split-face study to evaluate the
      effects of topical application of a Gold Silk Sericin/Niacinamide/Signaline
      complex on biophysical parameters related to skin ageing.
AB  - OBJECTIVE: To investigate the effects of topical application of a Gold Silk
      Sericin (GSS) complex on biophysical parameters related to skin ageing. METHODS:
      A range of non-invasive bioengineering methods were deployed in an 8-week
      randomized, double-blinded, vehicle-controlled, split-face study among 40 female
      subjects aged 40-70. Endpoints measured included expert grades of skin condition,
      stratum corneum (SC) hydration, SC barrier function, elasticity and surface
      topography. RESULTS: The GSS complex produced significant single-variable (P <
      0.05) improvements in SC hydration, barrier function, elasticity and surface
      topography compared with the Vehicle control. CONCLUSION: The GSS complex
      examined in this study represents an interesting new cosmetic topical technology
      with which to address multiple aspects of aged/photoaged female facial skin.

PMID- 25940760
TI  - Does the growth response of woody plants to elevated CO2 increase with
      temperature? A model-oriented meta-analysis.
AB  - The temperature dependence of the reaction kinetics of the Rubisco enzyme implies
      that, at the level of a chloroplast, the response of photosynthesis to rising
      atmospheric CO2 concentration (Ca ) will increase with increasing air
      temperature. Vegetation models incorporating this interaction predict that the
      response of net primary productivity (NPP) to elevated CO2 (eCa ) will increase
      with rising temperature and will be substantially larger in warm tropical forests
      than in cold boreal forests. We tested these model predictions against evidence
      from eCa experiments by carrying out two meta-analyses. Firstly, we tested for an
      interaction effect on growth responses in factorial eCa  * temperature
      experiments. This analysis showed a positive, but nonsignificant interaction
      effect (95% CI for above-ground biomass response = -0.8, 18.0%) between eCa and
      temperature. Secondly, we tested field-based eCa experiments on woody plants
      across the globe for a relationship between the eCa effect on plant biomass and
      mean annual temperature (MAT). This second analysis showed a positive but
      nonsignificant correlation between the eCa response and MAT. The magnitude of the
      interactions between CO2 and temperature found in both meta-analyses were
      consistent with model predictions, even though both analyses gave nonsignificant
      results. Thus, we conclude that it is not possible to distinguish between the
      competing hypotheses of no interaction vs. an interaction based on Rubisco
      kinetics from the available experimental database. Experiments in a wider range
      of temperature zones are required. Until such experimental data are available,
      model predictions should aim to incorporate uncertainty about this interaction. 

PMID- 25940762
TI  - Increased ICP promotes CaMKII-mediated phosphorylation of neuronal NOS at Ser847
      in the hippocampus immediately after subarachnoid hemorrhage.
AB  - Early brain injury has recently been identified as an indicator of poor prognosis
      after subarachnoid hemorrhage (SAH). Calmodulin-dependent protein kinase IIalpha
      (CaMKIIalpha) has been shown to phosphorylate neuronal NOS (nNOS) at Ser(847),
      resulting in a reduction in nNOS activity. In this study, we revealed
      chronological changes in the phosphorylation of nNOS at Ser(847) in the
      hippocampus and cortex immediately after SAH. In a rat single-hemorrhage model of
      SAH, the hippocampus and adjacent cortex were collected up to 24h after SAH.
      Samples from rats that were not injected with blood were used as controls. NOS
      was partially purified from the crude samples using ADP-agarose affinity
      chromatography. Western blot analysis revealed that nNOS phosphorylated (p-nNOS)
      at Ser(847) was significantly increased in the hippocampus, but not in the
      cortex, at 1h after SAH compared with that resulting from the control treatment.
      Immunoreactivity of p-nNOS at Ser(847) was observed in interneurons of the
      hippocampus at 1h after SAH. Injection of saline instead of blood also
      significantly induced p-nNOS at Ser(847) levels in the hippocampus at 1h after
      injection. The colocalization of CaMKIIalpha and nNOS was transiently increased
      in the hippocampus at 0.5h after SAH. Our data suggest that immediately after
      SAH, an increase in intracranial pressure might induce transient cerebral
      ischemia, potentially promoting the phosphorylation of nNOS at Ser(847) by
      CaMKIIalpha in the hippocampus. The activation of p-nNOS at Ser(847) in the
      hippocampus may alleviate ischemic insults immediately after SAH to exert a
      neuroprotective effect against early brain injury.

PMID- 25940761
TI  - Cancer-Associated Mutations in Breast Tumor Kinase/PTK6 Differentially Affect
      Enzyme Activity and Substrate Recognition.
AB  - Brk (breast tumor kinase, also known as PTK6) is a nonreceptor tyrosine kinase
      that is aberrantly expressed in several cancers and promotes cell proliferation
      and transformation. Genome sequencing studies have revealed a number of cancer
      associated somatic mutations in the Brk gene; however, their effect on Brk
      activity has not been examined. We analyzed a panel of cancer-associated
      mutations and determined that several of the mutations activate Brk, while two
      eliminated enzymatic activity. Three of the mutations (L16F, R131L, and P450L)
      are located in important regulatory domains of Brk (the SH3, SH2 domains, and C
      terminal tail, respectively). Biochemical data suggest that they activate Brk by
      disrupting intramolecular interactions that normally maintain Brk in an
      autoinhibited conformation. We also observed differential effects on recognition
      and phosphorylation of substrates, suggesting that the mutations can influence
      downstream Brk signaling by multiple mechanisms. 

PMID- 25940763
TI  - Upregulation of tissue inhibitor of metalloproteinase-1 contributes to
      restoration of the extracellular matrix in the rabbit basilar artery during
      cerebral vasospasm after subarachnoid hemorrhage.
AB  - Vascular remodeling caused by extracellular matrix (ECM) metabolism contributes
      to the development of cerebral vasospasm after subarachnoid hemorrhage (SAH). The
      balance between tissue inhibitor of metalloproteinases (TIMPs) and matrix
      metalloproteinases (MMPs) plays an important role in ECM remodeling. We
      investigated the mechanism of vascular remodeling following cerebral vasospasm in
      a rabbit double hemorrhage model. Rabbit basilar arteries were harvested on days
      3, 5, and 7 after initial hemorrhage. TIMP-1, TIMP-2, MMP-2, and MMP-9 mRNA and
      protein expression were investigated with microarray analysis, quantitative real
      time PCR, immunoblot analysis, and enzyme-linked immunosorbent assay (ELISA). The
      expression and localization of TIMP-1, TIMP-2, MMP-2, MMP-9, elastin,
      fibronectin, laminin, and collagens I, III, and IV were investigated with
      immuohistochemical staining. After SAH, TIMP-1 mRNA and protein expression were
      significantly increased on day 3 and then decreased to the control level on days
      5 and 7. MMP-9 protein expression was significantly increased on day 7. TIMP-2
      and MMP-2 mRNA and protein expression were significantly increased on day 7.
      Elastin, fibronectin, laminin, and collagens I, III, and IV protein expression
      was decreased on day 3 and then restored to control levels on day 7. Upregulation
      of TIMP-1 during the early phase of cerebral vasospasm may contribute to the
      recovery of the ECM during the late phase of cerebral vasospasm, resulting in a
      protective role of TIMP-1 from cerebral vasospasm. Moreover, the increase in
      arterial compliance by the decrease in ECM during the early phase of cerebral
      vasospasm may facilitate vasoconstriction of the cerebral artery. 

PMID- 25940764
TI  - Long-term cognitive dysfunction in the rat following docetaxel treatment is
      ameliorated by the phosphodiesterase-4 inhibitor, rolipram.
AB  - Clinical studies report evidence of long-term cognitive and other deficits
      following adjunctive chemotherapy treatment, which is often termed "chemobrain"
      or "chemo-fog". The neurological bases of these impairments are poorly
      understood. Here, we hypothesize that systemic chemotherapy treatment causes long
      term neurobehavioral deficits, and that these deficits are reversed by
      manipulation of cAMP by the PDE4 inhibitor, rolipram. Male han Wistar rats were
      treated with docetaxel (an adjunctive chemotherapeutic agent (1mg/kg i.v.)) or
      control solution (ethanol/Tween 20/0.9% Saline - 5/5/90) once per week for 4
      weeks. They were allowed to recover for 4 weeks, administration of rolipram
      (0.5mg/kg po) or vehicle (maple syrup) then began and continued daily for 4
      weeks. At the end of the treatment regime animals were tested for spatial and
      recognition memory deficits with the object exploration task and for depressive-
      and anxiety-like behavior in the forced swim test (FST) and open field
      exploration. We report docetaxel treatment impaired spatial memory but not object
      recognition memory, compared to control rats. Docetaxel-treated rats also spent
      significantly more time immobile than controls in the FST. Chronic rolipram
      treatment attenuated all of these docetaxel-associated changes, recovering
      spatial memory and reducing immobility. In conclusion, docetaxel-treated rats
      exhibit alterations in spatial memory and depressive-like behavior, which are
      reversed following chronic rolipram administration. These results detect long
      term cognitive and mood changes following docetaxel treatment and identify PDE4
      inhibition as a target treatment of neuropsychological changes associated with
      "chemobrain". 

PMID- 25940765
TI  - Behavioural, biochemical and molecular changes induced by chronic crack-cocaine
      inhalation in mice: The role of dopaminergic and endocannabinoid systems in the
      prefrontal cortex.
AB  - Crack-cocaine addiction has increasingly become a public health problem
      worldwide, especially in developing countries. However, no studies have focused
      on neurobiological mechanisms underlying the severe addiction produced by this
      drug, which seems to differ from powder cocaine in many aspects. This study
      investigated behavioural, biochemical and molecular changes in mice inhaling
      crack-cocaine, focusing on dopaminergic and endocannabinoid systems in the
      prefrontal cortex. Mice were submitted to two inhalation sessions of crack
      cocaine a day (crack-cocaine group) during 11 days, meanwhile the control group
      had no access to the drug. We found that the crack-cocaine group exhibited
      hyperlocomotion and a peculiar jumping behaviour ("escape jumping"). Blood
      collected right after the last inhalation session revealed that the
      anhydroecgonine methyl ester (AEME), a specific metabolite of cocaine pyrolysis,
      was much more concentrated than cocaine itself in the crack-cocaine group. Most
      genes related to the endocannabinoid system, CB1 receptor and cannabinoid
      degradation enzymes were downregulated after 11-day crack-cocaine exposition.
      These changes may have decreased dopamine and its metabolites levels, which in
      turn may be related with the extreme upregulation of dopamine receptors and
      tyrosine hydroxylase observed in the prefrontal cortex of these animals. Our data
      suggest that after 11 days of crack-cocaine exposure, neuroadaptive changes
      towards downregulation of reinforcing mechanisms may have taken place as a result
      of neurochemical changes observed on dopaminergic and endocannabinoid systems.
      Successive changes like these have never been described in cocaine hydrochloride
      models before, probably because AEME is only produced by cocaine pyrolysis and
      this metabolite may underlie the more aggressive pattern of addiction induced by
      crack-cocaine. 

PMID- 25940766
TI  - Testosterone application decreases the capacity for ACTH and corticosterone
      secretion in a rat model of the andropause.
AB  - The culminating phase of ageing in males-andropause is characterized by enhanced
      activity of the hypothalamic-pituitary-adrenal axis and frequent glucocorticoid
      excess. In parallel, free testosterone deficiency provides the baseline hormonal
      milieu for the ageing male. The aim of this study was to illustrate (using
      diverse microscopic and biochemical methodologies) the effects of testosterone
      application on the capacity for adrenocorticotropic hormone (ACTH) and
      corticosterone secretion in a rat model of the andropause. Middle-aged Wistar
      rats were divided into sham-operated (SO; n=8), orchidectomized (Orx; n=8) and
      testosterone treated orchidectomized (Orx+T; n=8) groups. Testosterone propionate
      (5 mg/kg b.w./day) was administered for three weeks, while SO and Orx groups
      received the vehicle alone. ACTH cells and the adrenal cortex were stained using
      immuno-histochemical, immuno-fluorescent and histochemical procedures.
      Circulating concentrations of testosterone, estradiol, ACTH and corticosterone,
      as well as the adrenal tissue corticosterone levels were measured by
      immunoassays. Testosterone application led to increased (p<0.05) serum
      concentrations of sex steroids. Consequently, in Orx+T rats the ACTH cell nuclei
      volume increased (p<0.05) by 34%, while the volume density of ACTH cells and
      their relative intensity of fluorescence decreased (p<0.05) by 46% and 21%,
      respectively, in comparison with the corresponding parameters in the Orx group.
      Testosterone also induced vasodilatation in the adrenocortical zona fasciculata,
      and decreased (p<0.05) the ACTH concentrations and adrenal tissue corticosterone
      levels by 38% and 31%, respectively, compared to the Orx group. In conclusion,
      testosterone administration caused a decrease in the capacity for ACTH and
      corticosterone secretion in a rat model of the andropause.

PMID- 25940767
TI  - Multisystemic Therapy Improves the Patient-Provider Relationship in Families of
      Adolescents with Poorly Controlled Insulin Dependent Diabetes.
AB  - The purpose of this study was to determine if multisystemic therapy (MST), an
      intensive, home and community-based family treatment, significantly improved
      patient-provider relationships in families where youth had chronic poor glycemic
      control. One hundred forty-six adolescents with type 1 or 2 diabetes in chronic
      poor glycemic control (HbA1c >=8 %) and their primary caregivers were randomly
      assigned to MST or a telephone support condition. Caregiver perceptions of their
      relationship with the diabetes multidisciplinary medical team were assessed at
      baseline and treatment termination with the Measure of Process of Care-20. At
      treatment termination, MST families reported significant improvement on the
      Coordinated and Comprehensive Care scale and marginally significant improvement
      on the Respectful and Supportive Care scale. Improvements on the Enabling and
      Partnership and Providing Specific Information scales were not significant.
      Results suggest MST improves the ability of the families and the diabetes
      treatment providers to work together. 

PMID- 25940768
TI  - Pharmacology of Bisphosphonates in Patients with Chronic Kidney Disease.
AB  - Bisphosphonates are medications which bind strongly to mineral. They are ingested
      by osteoclasts and inhibit an enzyme necessary for bone resorption. The
      gastrointestinal absorption is poor and the only method of excretion is renal.
      Therefore, in patients with CKD the body accumulates a higher percentage of a
      dose of bisphosphonate. These medications remain attached to bone mineral for
      many years. Although the primary action is to inhibit bone resorption,
      secondarily bone formation is also inhibited, and in patients with CKD
      bisphosphonate use often leads to adynamic bone. In some experimental models in
      animals, the bisphosphonates can inhibit vascular calcification but this effect
      has not been seen in humans. Intravenous bisphosphonates may cause renal damage
      but oral doses do not reduce creatinine clearance. In stage 3 CKD, in patients
      who still have normal PTH, calcium, and alkaline phosphatase, randomized trials
      show similar benefits as in patients without CKD. Data from stage 4 and 5 CKD are
      very limited and no clear benefit has been shown. 

PMID- 25940769
TI  - A descriptive and historical review of bibliometrics with applications to medical
      sciences.
AB  - The discipline of bibliometrics involves the application of mathematical and
      statistical methods to scholarly publications. The first attempts at systematic
      data collection were provided by Alfred Lotka and Samuel Bradford, who
      subsequently established the foundational laws of bibliometrics. Eugene Garfield
      ushered in the modern era of bibliometrics with the routine use of citation
      analysis and systematized processing. Key elements of bibliometric analysis
      include database coverage, consistency and accuracy of the data, data fields,
      search options, and analysis and use of metrics. A number of bibliometric
      applications are currently being used in medical science and health care.
      Bibliometric parameters and indexes may be increasingly used by grant funding
      sources as measures of research success. Universities may build benchmarking
      standards from bibliometric data to determine academic achievement through
      promotion and tenure guidelines in the future. This article reviews the history,
      definition, laws, and elements of bibliometric principles and provides examples
      of bibliometric applications to the broader health care community. To accomplish
      this, the Medline (1966-2014) and Web of Science (1945-2014) databases were
      searched to identify relevant articles; select articles were also cross
      referenced. Articles selected were those that provided background, history,
      descriptive analysis, and application of bibliometric principles and metrics to
      medical science and health care. No attempt was made to cover all areas
      exhaustively; rather, key articles were chosen that illustrate bibliometric
      concepts and enhance the reader's knowledge. It is important that faculty and
      researchers understand the limitations and appropriate uses of bibliometric data.
      Bibliometrics has considerable potential as a research area for health care
      scientists and practitioners that can be used to discover new information about
      academic trends, pharmacotherapy, disease, and broader health sciences trends. 

PMID- 25940770
TI  - Characterisation of a multidrug-resistant Bacteroides fragilis isolate recovered
      from blood of a patient in Denmark using whole-genome sequencing.
AB  - Here we describe a patient undergoing extensive abdominal surgery and
      hyperthermic intraperitoneal chemotherapy due to primary adenocarcinoma in the
      sigmoid colon with peritoneal carcinomatosis. During hospitalisation the patient
      suffered from bacteraemia with a multidrug-resistant Bacteroides fragilis
      isolate. Whole-genome sequencing of the isolate resulted in identification of
      nimE, cfiA and ermF genes corresponding to metronidazole, carbapenem and
      clindamycin resistance. 

PMID- 25940771
TI  - Rethinking the roles of inflammation in the intracerebral hemorrhage.

PMID- 25940772
TI  - Vitamin D controls apoptosis and proliferation of cutaneous T-cell lymphoma
      cells.

PMID- 25940779
TI  - A slippery molecular assembly allows water as a self-erasable security marker.
AB  - Protection of currency and valuable documents from counterfeit continues to be a
      challenge. While there are many embedded security features available for document
      safety, they are not immune to forgery. Fluorescence is a sensitive property,
      which responds to external stimuli such as solvent polarity, temperature or
      mechanical stress, however practical use in security applications is hampered due
      to several reasons. Therefore, a simple and specific stimuli responsive security
      feature that is difficult to duplicate is of great demand. Herein we report the
      design of a fluorescent molecular assembly on which water behaves as a self
      erasable security marker for checking the authenticity of documents at point of
      care. The underlying principle involves the disciplined self-assembly of a tailor
      made fluorescent molecule, which initially form a weak blue fluorescence
      (lambdaem = 425 nm, Phif = 0.13) and changes to cyan emission (lambdaem = 488
      nm,Phif = 0.18) in contact with water due to a reversible molecular slipping
      motion. This simple chemical tool, based on the principles of molecular self
      assembly and fluorescence modulation, allows creation of security labels and
      optically masked barcodes for multiple documents authentication.

PMID- 25940773
TI  - Evaluation of Early Reperfusion Criteria in Acute Ischemic Stroke.
AB  - BACKGROUND AND PURPOSE: Though still debated, early reperfusion is increasingly
      used as a biomarker for clinical outcome. However, the lack of a standard
      definition hinders the assessment of reperfusion therapies and study comparisons.
      The objective was to determine the optimal early reperfusion criteria that
      predicts clinical outcome in ischemic stroke. METHODS: Early reperfusion was
      assessed voxel-wise in 57 patients within 6 hours of symptom onset. The
      performance of the time to peak (TTP), the mean transit time (MTT), and the time
      to maximum of residue function (Tmax ) at various delays thresholds in predicting
      the neurological response (based on the National Institutes of Health Stroke
      Scale) and the functional outcome (modified Rankin scale <=1) at 1 month were
      compared. A receiver operating characteristics (ROC) analysis determined the
      optimal extent of reperfusion. A novel unsupervised classification of reperfusion
      using group-based trajectory modeling (GBTM) was evaluated. RESULTS: MTT had a
      lower performance than TTP and Tmax in predicting the neurological response (P =
      .008 vs. TTP and P = .006 vs. Tmax ) or the functional outcome (P = .0006 vs.
      TTP; P = .002 vs. Tmax ). No delay threshold had a significantly higher
      predictive value than another. The optimal percentage of reperfusion was
      dependent on the outcome scale (P < .001). The GBTM-based classification of
      reperfusion was closely associated with the clinical outcome and had a similar
      accuracy compared to ROC-based classification. CONCLUSIONS: TTP and Tmax should
      be preferred to MTT in defining early reperfusion. GBTM provided a clinically
      relevant reperfusion classification that does not require prespecified delay
      thresholds or clinical outcomes.

PMID- 25940780
TI  - Chondroprotective effect of zinc oxide nanoparticles in conjunction with hypoxia
      on bovine cartilage-matrix synthesis.
AB  - Articular cartilage is a tissue specifically adapted to a specific niche with a
      low oxygen tension (hypoxia), and the presence of such conditions is a key factor
      in regulating growth and survival of chondrocytes. Zinc deficiency has been
      linked to cartilage-related disease, and presence of Zinc is known to provide
      antibacterial benefits, which makes its inclusion attractive in an in vitro
      system to reduce infection. Inclusion of 1% zinc oxide nanoparticles (ZnONP) in
      poly octanediol citrate (POC) polymer cultured in hypoxia has not been well
      determined. In this study we investigated the effects of ZnONP on chondrocyte
      proliferation and matrix synthesis cultured under normoxia (21% O2 ) and hypoxia
      (5% O2 ). We report an upregulation of chondrocyte proliferation and sulfated
      glycosaminoglycan (S-GAG) in hypoxic culture. Results demonstrate a synergistic
      effect of oxygen concentration and 1% ZnONP in up-regulation of anabolic gene
      expression (Type II collagen and aggrecan), and a down regulation of catabolic
      (MMP-13) gene expression. Furthermore, production of transcription factor hypoxia
      inducible factor 1A (HIF-1A) in response to hypoxic condition to regulate
      chondrocyte survival under hypoxia is not affected by the presence of 1% ZnONP.
      Presence of 1% ZnONP appears to act to preserve homeostasis of cartilage in its
      hypoxic environment.

PMID- 25940781
TI  - Reply: To PMID 25370956.

PMID- 25940782
TI  - Endothelial nitric oxide synthase polymorphisms and erectile dysfunction: a meta
      analysis.
AB  - INTRODUCTION AND AIMS: Erectile dysfunction (ED) is a frequent disorder in men
      and has a serious impact on the quality of the patient's life. Recent studies
      have examined the relationship between endothelial nitric oxide synthase (eNOS)
      polymorphisms and ED. However, the results remain inconclusive. The present study
      aimed to offer an actual view of estimating the correlation between eNOS
      polymorphisms and ED. METHODS: We performed a meta-analysis to estimate the
      association between eNOS polymorphisms and ED risk. Databases employed for data
      mining until December 1, 2014 included PubMed, Web of Science, and the Chinese
      National Knowledge Infrastructure. Two study investigators independently
      conducted a literature search and data extraction. Odds ratios (ORs) with 95%
      confidence intervals for the risk were calculated by using a random effects model
      or fixed effects model. RESULTS: A total of 20 studies in 13 publications
      increased ED risk in allele contrast, dominant, heterozygote, and homozygote
      models (allele contrast: OR = 1.514, 95% confidence interval were included in the
      meta-analysis. In the overall comparison, the eNOS G984T polymorphism was
      associated with an [CI]: 1.019-2.248). For 4 VNTR polymorphisms, the overall
      analysis showed a significant association between homozygote comparison and
      recessive genetic model (homozygote comparison: OR = 1.917, CI: 1.073-3.424). The
      eNOS T786C polymorphism increased ED risk in allele contrast, homozygote, and
      recessive models (allele contrast: OR = 1.588, CI: 1.316-1.915). Significant
      heterogeneity was mainly observed in studies on the G894T polymorphism. No
      publication bias was detected in all of the variants. CONCLUSION: The eNOS
      polymorphisms G894T, 4 VNTR, and T786C were associated with an increased risk for
      ED. However, these results are still preliminary. Further studies based on
      different confounders and using a large population size should be conducted to
      generate more accurate and reliable conclusions.

PMID- 25940783
TI  - Subdiaphragmatic vagotomy enhances stress-induced epinephrine release in rats.
AB  - Neuroendocrine stress response is regulated by several feedback loops. Since it
      has been suggested that afferent vagal pathways contribute to these feedback
      loops, we examined the effect of surgical subdiaphragmatic vagotomy on both
      baseline and stress-induced increases in plasma epinephrine, norepinephrine, and
      corticosterone levels in vagotomized and sham-operated Sprague Dawley rats. On
      either the 3rd or 14th day following vagotomy, the animals were exposed to acute
      immobilization stress and blood from the jugular vein was collected both before
      and during stress exposure. We found that vagotomy significantly enhanced
      immobilization-induced increases of plasma epinephrine, norepinephrine, and
      corticosterone levels on the 3rd day following surgery. However, on the 14th day
      following surgery, vagotomy enhanced only increase of plasma epinephrine levels
      in stressed rats. Our data indicate that afferent pathways of the vagus nerve are
      involved in negative feedback regulation of epinephrine secretion from the
      adrenal medulla during stressful conditions. We hypothesize that this feedback
      mechanism might be mediated by the binding of circulating epinephrine on beta2
      adrenergic receptors localized on sensory endings of the vagus nerve. 

PMID- 25940784
TI  - Dynamics of Notch signalling in the mouse oviduct and uterus during the oestrous
      cycle.
AB  - The oviduct and uterus undergo extensive cellular remodelling during the oestrous
      cycle, requiring finely tuned intercellular communication. Notch is an
      evolutionarily conserved cell signalling pathway implicated in cell fate
      decisions in several tissues. In the present study we evaluated the quantitative
      real-time polymerase chain reaction (real-time qPCR) and expression
      (immunohistochemistry) patterns of Notch components (Notch1-4, Delta-like 1
      (Dll1), Delta-like 4 (Dll4), Jagged1-2) and effector (hairy/enhancer of split
      (Hes) 1-2, Hes5 and Notch-Regulated Ankyrin Repeat-Containing Protein (Nrarp))
      genes in the mouse oviduct and uterus throughout the oestrous cycle. Notch genes
      are differentially transcribed and expressed in the mouse oviduct and uterus
      throughout the oestrous cycle. The correlated transcription levels of Notch
      components and effector genes, and the nuclear detection of Notch effector
      proteins, indicate that Notch signalling is active. The correlation between
      transcription levels of Notch genes and progesterone concentrations, and the
      association between expression of Notch proteins and progesterone receptor (PR)
      activation, indicate direct progesterone regulation of Notch signalling. The
      expression patterns of Notch proteins are spatially and temporally specific,
      resulting in unique expression combinations of Notch receptor, ligand and
      effector genes in the oviduct luminal epithelium, uterus luminal and glandular
      epithelia and uterine stroma throughout the oestrous cycle. Together, the results
      of the present study imply a regulatory role for Notch signalling in oviduct and
      uterine cellular remodelling occurring throughout the oestrous cycle.

PMID- 25940785
TI  - Rosiglitazone-activated PPARgamma induces neurotrophic factor-alpha1
      transcription contributing to neuroprotection.
AB  - Brain peroxisome proliferator-activated receptor gamma (PPARgamma), a member of
      the nuclear receptor superfamily of ligand-dependent transcription factors, is
      involved in neuroprotection. It is activated by the drug rosiglitazone, which
      then can increase the pro-survival protein B-cell lymphoma 2 (BCL-2), to mediate
      neuroprotection. However, the mechanism underlying this molecular cascade remains
      unknown. Here, we show that the neuroprotective protein neurotrophic factor
      alpha1 (NF-alpha1), which also induces the expression of BCL-2, has a promoter
      that contains PPARgamma-binding sites that are activated by rosiglitazone.
      Treatment of Neuro2a cells and primary hippocampal neurons with rosiglitazone
      increased endogenous NF-alpha1 expression and prevented H2 O2 -induced
      cytotoxicity. Concomitant with the increase in NF-alpha1, BCL-2 was also
      increased in these cells. When siRNA against NF-alpha1 was used, the induction of
      BCL-2 by rosiglitazone was prevented, and the neuroprotective effect of
      rosiglitazone was reduced. These results demonstrate that rosiglitazone-activated
      PPARgamma directly induces the transcription of NF-alpha1, contributing to
      neuroprotection in neurons. We proposed the following cascade for neuroprotection
      against oxidative stress by rosiglitazone: Rosiglitazone enters the neuron and
      binds to peroxisome proliferator-activated receptor gamma (PPARgamma) in the
      nucleus. The PPARgamma-rosiglitazone complex binds to the neurotrophic factor
      alpha1 (NF-alpha1) promoter and activates the transcription of NF-alpha1 mRNA
      which is then translated to the protein. NF-alpha1 is the secreted, binds to a
      cognate receptor and activates the extracellular signal-regulated kinases (ERK)
      pathway. This in turn enhances the expression of the pro-survival protein, B-cell
      lymphoma 2 (BCL-2) and inhibition of caspase 3 (Csp-3) to mediate neuroprotection
      under oxidative stress. Akt, protein kinase B (PKB). 

PMID- 25940786
TI  - Cysticercosis and epilepsy in rural Tanzania: a community-based case-control and
      imaging study.
AB  - OBJECTIVE: To assess the contribution of neurocysticercosis (NCC) to the burden
      of epilepsy in a rural Tanzanian population. METHODS: We identified adult people
      with epilepsy (PWE) in a door-to-door study in an established demographic
      surveillance site. PWE and community controls were tested for antibodies to
      Taenia solium, the causative agent of NCC, and all PWE were offered a computed
      tomography (CT) head scan. Data on household occupancy and sanitation, pig
      keeping and pork consumption were collected from PWE and controls and
      associations with epilepsy were assessed using chi-square or Fisher's exact
      tests. RESULTS: Six of 218 PWE had antibodies to T. solium (2.8%; 95% CI 0.6
      4.9), compared to none of 174 controls (Fisher's exact test, P = 0.04). Lesions
      compatible with NCC were seen in eight of 200 CT scans (4.0%; 95% CI 1.3-6.7). A
      total of 176 PWE had both investigations of whom two had positive serology along
      with NCC-compatible lesions on CT (1.1%; 95% 0.3-4.0). No associations between
      epilepsy and any risk factors for NCC were identified. CONCLUSIONS:
      Neurocysticercosis is present in this population but at a lower prevalence than
      elsewhere in Tanzania and sub-Saharan Africa. Insights from low-prevalence areas
      may inform public health interventions designed to reduce the burden of
      preventable epilepsy.

PMID- 25940787
TI  - Molecular epidemiology of human Herpesviruses types 1-6 and 8 among Greek blood
      donors.
AB  - BACKGROUND: Human Herpesviruses (HHVs) maintain life-long latent persistence in
      the majority of the adult population including blood donors. The necessity for
      their study resides in the potential risk of transfusion-associated infection and
      the subsequent complications in the immunocompromised host. We aimed to assess
      the prevalence of HHVs types 1-6 and 8 among healthy blood donors of Thessaly
      prefecture in order to evaluate the frequency distribution of HHVs in Greek
      population and to ascertain possible correlations with demographic factors.
      MATERIALS AND METHODS: Polymerase chain reaction (PCR) detection of HHVs DNA was
      determined in 401 randomly selected consecutive blood donors of Central Greece.
      Epidemiological data were recorded through a well structured questionnaire.
      RESULTS: The overall PCR positivity for HHVs was 25.4%. HHVs types 1-3 were not
      detected in any donor sample. A specimen with high level of HHV-6 DNA (1,580,400
      copies per mL) was recorded. HHV-4 DNA positivity was significantly associated
      with rural residency. CONCLUSION: HHV-4 DNA is commonly detected in whole blood
      specimens of healthy individuals. HHVs types 5, 6 and 8 are rarely detected.
      However, the existence of a donor sample with high HHV-6 viral load raises
      questions regarding the potential risk of HHV-6 blood-borne infection and the
      safety of blood products.

PMID- 25940789
TI  - Exosome isolation: a microfluidic road-map.
AB  - Exosomes, first isolated 30 years ago, are nanoscale vesicles shed by most types
      of cells. The nucleic acid rich content of these nanoparticles, floating in
      virtually all bodily fluids, has great potential for non-invasive molecular
      diagnostics and may represent a novel therapeutic delivery system. However,
      current isolation techniques such as ultracentrifugation are not convenient and
      do not result in high purity isolation. This represents an interesting challenge
      for microfluidic technologies, from a cost-effective perspective as well as for
      enhanced purity capabilities, and point-of-care acquisition and diagnosis. In
      this frontier review, we present the current challenges, comment the first
      microfluidic advances in this new field and propose a roadmap for future
      developments. This review enables biologists and clinicians familiar with exosome
      enrichment to assess the performance of novel microfluidic devices and, equally,
      enables microfluidic engineers to educate themselves about this new class of
      promising biomarker-rich particles and the challenges arising from their clinical
      use. 

PMID- 25940790
TI  - BICUVOX.1-matrix composite electrolyte with yttria-stabilized zirconia as an
      inert phase: SEM evaluation of the chemical stability under hydrogen atmosphere.
AB  - The purpose of this study is to evaluate the efficacy of yttria-stabilized
      zirconia (3Y-TZP) as an inert phase to prevent the decomposition of Bi2 V0.9
      Cu0.1 O5.5 -delta (BICUVOX.1) electrolyte under reducing atmosphere. A post
      mortem scanning electron microscopy (SEM) study was performed after chemical
      stability tests under hydrogen-rich atmosphere using a Sieverts-type apparatus.
      SEM results showed that BICUVOX.1 decomposition starts under a hydrogen pressure
      of 19.7 atm at 300 degrees C, even in the case of the composite containing 3Y
      TZP. The microstructure of BICUVOX.1 after decomposition was observed to be
      composed of microspheres ranging from 10 to 100 um formed primarily of metallic
      bismuth. In the composite, in addition to microspheres, the microstructure
      contained bismuth fibers growth from the grain area of the BICUVOX.1 matrix.
      Despite significant surface morphological modifications, the grain-boundary
      arranged 3Y-TZP particles in a BICUVOX.1-matrix composite did not result in
      enhanced chemical stability.

PMID- 25940788
TI  - Differential parenting and risk for psychopathology: a monozygotic twin
      difference approach.
AB  - PURPOSE: Consistent and non-specific associations have been found between
      parenting style and major depression, anxiety disorders, and externalizing
      behavior. Although often considered part of twins' shared environment, parenting
      can also be conceptualized as non-shared environment. Non-shared environmental
      influences have important effects on development but are difficult to test and
      sort out because of the possible confounding effects of gene-environment
      interactions and evocative gene-environment correlations. The monozygotic (MZ)
      differences approach is one way to analytically investigate non-shared
      environment. METHODS: The aim of the present study is to use the MZ differences
      approach to investigate the relationship between differential parenting among
      1303 twin pairs (mean age 36.69 +/- 8.56) and differences in total symptom counts
      of major depression (MD), generalized anxiety disorder (GAD), conduct disorder
      (CD), and anti-social behavior (ASB) during adulthood. RESULTS: Although effect
      sizes tended to be small, a number of results were significantly different from
      zero. Perceived differences in parental coldness was positively associated with
      internalizing disorders. Differences in protectiveness were negatively associated
      with MD, GAD, and ASB. Differences in authoritarianism were positively associated
      with MD and CD, but negatively associated with ASB. CONCLUSIONS: Perceived
      differences in parenting style are associated with differences in MD, GAD, CD,
      and ASB outcomes in a sample of MZ twins. Despite the lack of a basis for making
      causal inferences about parenting style and psychopathology, these results are
      suggestive of such a relationship and show that non-shared environmental
      influence of parenting does in some cases significantly predict adult
      psychopathology.

PMID- 25940791
TI  - Influence of Smoking Status and Intensity on Discovery of Blood Pressure Loci
      Through Gene-Smoking Interactions.
AB  - BACKGROUND: Genetic variation accounts for approximately 30% of blood pressure
      (BP) variability but most of that variability has not been attributed to specific
      variants. Interactions between genes and BP-associated factors may explain some
      "missing heritability." Cigarette smoking increases BP after short-term exposure
      and decreases BP with longer exposure. Gene-smoking interactions have discovered
      novel BP loci, but the contribution of smoking status and intensity to gene
      discovery is unknown. METHODS: We analyzed gene-smoking intensity interactions
      for association with systolic BP (SBP) in three subgroups from the Framingham
      Heart Study: current smokers only (N = 1,057), current and former smokers ("ever
      smokers," N = 3,374), and all subjects (N = 6,710). We used three smoking
      intensity variables defined at cutoffs of 10, 15, and 20 cigarettes per day
      (CPD). We evaluated the 1 degree-of-freedom (df) interaction and 2df joint test
      using generalized estimating equations. RESULTS: Analysis of current smokers
      using a CPD cutoff of 10 produced two loci associated with SBP. The rs9399633
      minor allele was associated with increased SBP (5 mmHg) in heavy smokers (CPD >
      10) but decreased SBP (7 mmHg) in light smokers (CPD <= 10). The rs11717948 minor
      allele was associated with decreased SBP (8 mmHg) in light smokers but decreased
      SBP (2 mmHg) in heavy smokers. Across all nine analyses, 19 additional loci
      reached P < 1 * 10(-6). DISCUSSION: Analysis of current smokers may have the
      highest power to detect gene-smoking interactions, despite the reduced sample
      size. Associations of loci near SASH1 and KLHL6/KLHL24 with SBP may be modulated
      by tobacco smoking.

PMID- 25940793
TI  - An erythematous nodule on the nipple: An unusual presentation of primary
      syphilis.

PMID- 25940792
TI  - Chronic lymphocytic leukaemia induces an exhausted T cell phenotype in the TCL1
      transgenic mouse model.
AB  - Although chronic lymphocytic leukaemia (CLL) is a B cell malignancy, earlier
      studies have indicated a role of T cells in tumour growth and disease
      progression. In particular, the functional silencing of antigen-experienced T
      cells, called T cell exhaustion, has become implicated in immune evasion in CLL.
      In this study, we tested whether T cell exhaustion is recapitulated in the
      TCL1(tg) mouse model for CLL. We show that T cells express high levels of the
      inhibitory exhaustion markers programmed cell death 1 (PDCD1, also termed PD-1)
      and lymphocyte-activation gene 3 (LAG3), whereas CLL cells express high levels of
      CD274 (also termed PD-ligand 1). In addition, the fraction of exhausted T cells
      increases with CLL progression. Finally, we demonstrate that exhausted T cells
      are reinvigorated towards CLL cytotoxicity by inhibition of PDCD1/CD274
      interaction in vivo. These results suggest that T cell exhaustion contributes to
      CLL pathogenesis and that interference with PDCD1/CD274 signalling holds high
      potential for therapeutic approaches. 

PMID- 25940795
TI  - PDL1 expression in inflammatory breast cancer is frequent and predicts for the
      pathological response to chemotherapy.
AB  - We retrospectively analyzed PDL1 mRNA expression in 306 breast cancer samples,
      including 112 samples of an aggressive form, inflammatory breast cancer (IBC).
      PDL1 expression was heterogeneous, but was higher in IBC than in non-IBC.
      Compared to normal breast samples, PDL1 was overexpressed in 38% of IBC. In IBC,
      PDL1 overexpression was associated with estrogen receptor-negative status, basal
      and ERBB2-enriched aggressive subtypes, and clinico-biological signs of anti
      tumor T-cell cytotoxic response. PDL1 overexpression was associated with better
      pathological response to chemotherapy, independently of histo-clinical variables
      and predictive gene expression signatures. No correlation was found with
      metastasis-free and overall specific survivals. In conclusion, PDL1
      overexpression in IBC correlated with better response to chemotherapy. This
      seemingly counterintuitive correlation between expression of an immunosuppressive
      molecule and improved therapeutic response may be resolved if PDL1 expression is
      viewed as a surrogate marker of a strong antitumor immune response among patients
      treated with immunogenic chemotherapy. In such patients, PDL1 inhibition could
      protect activated T-cells or reactivate inhibited T-cells and improve the
      therapeutic response, notably when associated with immunogenic chemotherapy. 

PMID- 25940796
TI  - Pregnancy associated plasma protein-A links pregnancy and melanoma progression by
      promoting cellular migration and invasion.
AB  - Melanoma is the most common cancer diagnosed in pregnant women and an aggressive
      course with poorer outcomes is commonly described during pregnancy or shortly
      after childbirth. The underlying mechanisms for this are not understood. Here, we
      report that melanoma migration, invasiveness and progression are promoted by
      Pregnancy-Associated Plasma Protein-A (PAPPA), a pregnancy-associated
      metalloproteinase produced by the placenta that increases the bioavailability of
      IGF1 by cleaving it from a circulating complex formed with IGFBP4. We show that
      PAPPA is widely expressed by metastatic melanoma tumors and is elevated in
      melanoma cells exhibiting mesenchymal, invasive and label-retaining phenotypes.
      Notably, inhibition of PAPPA significantly reduced invasion and migration of
      melanoma cells in vitro and in vivo within the embryonic chicken neural tube.
      PAPPA-enriched pregnancy serum treatment enhanced melanoma motility in vitro.
      Furthermore, we report that IGF1 can induce the phenotypic and functional effects
      of epithelial-to-mesenchymal transition (EMT) in melanoma cells. In this study,
      we establish a clear relationship between a pregnancy-associated protein PAPPA,
      melanoma and functional effects mediated through IGF1 that provides a plausible
      mechanism for accelerated melanoma progression during pregnancy. This opens the
      possibility of targeting the PAPPA/IGF1 axis therapeutically.

PMID- 25940797
TI  - Thyroid hormone-mediated regulation of lipocalin 2 through the Met/FAK pathway in
      liver cancer.
AB  - The thyroid hormone, 3,3',5-triiodo-L-thyronine (T3), regulates cell growth,
      development and differentiation via interactions with thyroid hormone receptors
      (TR), but the mechanisms underlying T3-mediated modulation of cancer progression
      are currently unclear. Lipocalin 2 (LCN2), a tumor-associated protein, is
      overexpressed in a variety of cancer types. Oligonucleotide microarray, coupled
      with proteomic analysis, has revealed that LCN2 is positively regulated by T3/TR.
      However, the physiological role and pathway of T3-mediated regulation of LCN2 in
      hepatocellular carcinogenesis remain to be characterized. Upregulation of LCN2
      after T3 stimulation was observed in a time- and dose-dependent manner.
      Additionally, TRE on the LCN2 promoter was identified at positions -1444/-1427.
      Overexpression of LCN2 enhanced tumor cell migration and invasion, and
      conversely, its knockdown suppressed migration and invasion, both in vitro and in
      vivo. LCN2-induced migration occurred through activation of the Met/FAK cascade.
      LCN2 was overexpressed in clinical hepatocellular carcinoma (HCC) patients,
      compared with normal subjects, and positively correlated with TRalpha levels.
      Both TRalpha and LCN2 showed similar expression patterns in relation to survival
      rate, tumor grade, tumor stage and vascular invasion. Our findings collectively
      support a potential role of T3/TR in cancer progression through regulation of
      LCN2 via the Met/FAK cascade. LCN2 may thus be effectively utilized as a novel
      marker and therapeutic target in HCC. 

PMID- 25940800
TI  - Disseminated cat-scratch disease: case report and review of the literature.
AB  - Cat scratch disease (CSD) can present as a systemic disease in 5-10% of cases and
      lead to various disease entities. A previously healthy 16-month-old boy presented
      with fever for 7 days without other obvious symptoms. Abdominal computed
      tomography scan demonstrated enlarged right inguinal lymph nodes and multiple
      small round hypodensities in the spleen. Despite antibiotic treatment for 1 week,
      the fever persisted and the intrasplenic lesions progressed. Inguinal lymph node
      biopsy confirmed CSD by immunohistochemistry staining. The diagnosis of CSD was
      also supported by a history of contact, imaging and serological findings. The
      patient recovered after treatment with azithromycin for a total of 5 weeks and,
      in serial follow-up, the hepatosplenic micro-abscesses resolved after 4th months.

PMID- 25940798
TI  - Inhibition of histamine receptor 3 suppresses glioblastoma tumor growth,
      invasion, and epithelial-to-mesenchymal transition.
AB  - Histamine receptor 3 (H3R) is expressed in various tumors and correlated with
      malignancy and tumor proliferation. However, the role of H3R in tumor invasion
      and epithelial to mesenchymal transition (EMT) remains unknown. Here, we explored
      the H3R in the highly invasive glioblastoma (GBM) and U87MG cells. We found that
      H3R mRNA and protein levels were up-regulated in the GBM and glioma cell lines
      compared to normal brain tissue and astrocytes. In U87MG cell line, inhibition of
      H3R by siRNA or the antagonist ciproxifan (CPX) suppressed proliferation,
      invasiveness, and the expression of EMT activators (Snail, Slug and Twist). In
      addition, expression of epithelial markers (E-cadherin and ZO-1) was up-regulated
      and expression of mesenchymal markers (vimentin and N-cadherin) was down
      regulated in vitro and in vivo in a xenograft model. In addition, we also showed
      that inhibition of H3R by siRNA or CPX inactivated the PI3K/Akt and MEK/ERK
      signaling pathways, while inhibition of Akt or ERK activity with antagonists or
      siRNAs suppressed H3R agonist (R)-(alpha)-(-)- methylhistamine dihydrobromide
      (RAMH) mediated invasion and reorganization of cadherin-household. In conclusion,
      overexpression of H3R is associated with glioma progression. Inhibition of H3R
      leads to suppressed invasion and EMT of GBM by inactivating the PI3K/Akt and
      MEK/ERK pathways in gliomas. 

PMID- 25940805
TI  - Growth in Western Australian emergency department demand during 2007-2013 is due
      to people with urgent and complex care needs.
AB  - OBJECTIVES: To determine the magnitude and characteristics of the increase in ED
      demand in Western Australia (WA) from 2007 to 2013. METHODS: We conducted a
      population-based longitudinal study examining trends in ED demand, stratified by
      area of residence, age group, sex, Australasian Triage Scale category and
      discharge disposition. The outcome measures were annual number and rate of ED
      presentations. We calculated average annual growth, and age-specific and age
      standardised rates. We assessed the statistical significance of trends, overall
      and within each category, using the Mann-Kendall trend test and analysis of
      variance ANOVA. We also calculated the proportions of growth in ED demand that
      were attributable to changes in population and utilisation rate. RESULTS: From
      2007 to 2013, ED presentations increased by an average 4.6% annually from 739,742
      to 945,244. The rate increased 1.4% from 354.1 to 382.6 per 1000 WA population (P
      = 0.02 for the trend). The main increase occurred in metropolitan WA, age 45+
      years, triage category 2 and 3 and admitted cohorts. Approximately three-quarters
      of this increase was due to population change (growth and ageing) and one-quarter
      due to increase in utilisation. CONCLUSION: Our study reveals a 4.6% annual
      increase in ED demand in WA in 2007-2013, mostly because of an increase in people
      with urgent and complex care needs, and not a shift (demand transfer) from
      primary care. This indicates that a system-wide integrated approach is required
      for demand management.

PMID- 25940801
TI  - Non-steady-state hematopoiesis regulated by the C/EBPbeta transcription factor.
AB  - Steady-state hematopoiesis responds to extracellular stimuli to meet changing
      demands and also to pathologically altered intracellular signaling. Granulocyte
      production increases following infection or in response to cytokine stimulation,
      and activation of the CCAAT/enhancer-binding protein beta (C/EBPbeta)
      transcription factor is required for such stress-induced granulopoiesis, whereas
      C/EBPalpha plays a critical role in maintaining steady-state granulopoiesis.
      Different roles of these C/EBP transcription factors in different modes of
      hematopoiesis are evolutionally conserved from zebrafish to humans. In addition
      to reactions against infections, C/EBPbeta is responsible for cancer-driven
      myelopoiesis, which promotes cancer progression, at least in part, by abrogating
      the immune response in the cancer microenvironment. The BCR-ABL fusion protein
      activates emergency-specific pathway of granulopoiesis by upregulating C/EBPbeta.
      This in turn causes chronic phase chronic myeloid leukemia, which is
      characterized by myeloid expansion. The C/EBPbeta transcription factor also plays
      a role in other hematological malignancies of both myeloid and lymphoid lineage
      origin. Thus, elucidation of the upstream and downstream networks surrounding
      C/EBPbeta will lead to the development of novel therapeutic strategies for
      diseases mediated by non-steady-state hematopoiesis. 

PMID- 25940806
TI  - Catalytic, oxidant-free, direct olefination of alcohols using Wittig reagents.
AB  - Reported here is the catalytic, acceptorless coupling of alcohols with in situ
      generated, non-stabilized phosphonium ylides to form olefins as major products.
      The reaction uses low catalyst loadings and does not require added oxidants.
      Hydrogenation of the product is minimized and the reaction leads to Z (aliphatic)
      or E (benzylic) stereospecificity. 

PMID- 25940807
TI  - Coordination and symmetry patterns during the drop vertical jump, 6-months after
      first-time lateral ankle sprain.
AB  - To evaluate the adaptive movement and motor control patterns of a group with a 6
      month history of first-time lateral ankle sprain (LAS) injury during a drop
      vertical jump (DVJ) task. Fifty-one participants with a 6-month history of first
      time acute LAS injury and twenty controls performed a DVJ task. 3D kinematic and
      sagittal plane kinetic profiles were plotted for the lower extremity joints of
      both limbs for the drop jump (phase 1) and drop landing (phase 2) phases of the
      DVJ. Inter-limb symmetry and the rate of impact modulation (RIM) relative to
      bodyweight (BW) during both phases of the DVJ were also determined. LAS
      participants displayed bilateral increases in knee flexion and an increase in
      ankle inversion during phases 1 and 2, respectively. They also displayed reduced
      ankle plantar flexion on their injured limb during both phases of the DVJ (p <
      0.05); increased inter-limb asymmetry of RIM was noted for both phases of the
      DVJ, while the moment-of-force profile exhibited bilaterally greater hip extensor
      dominance during phase 1. Participants with a 6-month history of first-time LAS
      display some movement patterns consistent with those observed in chronic ankle
      instability populations during similar tasks.

PMID- 25940808
TI  - Tissue engineering: new tools for old problems.

PMID- 25940809
TI  - Synthesis, Characterization, and Theoretical Investigation of Two-Coordinate
      Palladium(0) and Platinum(0) Complexes Utilizing pi-Accepting Carbenes.
AB  - An elegant general synthesis route for the preparation of two coordinate
      palladium(0) and platinum(0) complexes was developed by reacting commercially
      available tetrakis(triphenylphosphine)palladium/platinum with pi-accepting cyclic
      alkyl(amino) carbenes (cAACs). The complexes are characterized by NMR
      spectroscopy, mass spectrometry, and single-crystal X-ray diffraction. The
      palladium complexes exhibit sharp color changes (crystallochromism) from dark
      maroon to bright green if the C-Pd-C bond angle is sharpened by approximately 6
      degrees , which is chemically feasible by elimination of one lattice THF solvent
      molecule. The analogous dark orange-colored platinum complexes are more rigid and
      thus do not show this phenomenon. Additionally, [(cAAC)2 Pd/Pt] complexes can be
      quasi-reversibly oxidized to their corresponding [(cAAC)2 Pd/Pt](+) cations, as
      evidenced by cyclic voltammetry measurements. The bonding and stability are
      studied by theoretical calculations. 

PMID- 25940810
TI  - Combination Systemic Fluorouracil and Radiation for the Treatment of Recalcitrant
      Condyloma with Associated Squamous Cell Carcinoma in an Immunocompromised 15-Year
      Old Girl.
AB  - Condylomata acuminata (CA), or anogenital warts, are typically benign lesions
      caused by human papillomavirus infection. Although they are rare,
      immunocompromised individuals are at a higher risk of CA undergoing
      transformation into invasive anal squamous cell carcinoma (SCC). These patients
      need aggressive evaluation and management. Treatment of CA is challenging,
      particularly for immunocompromised hosts, in whom warts are resistant to
      treatment and commonly recur. Currently, there is no gold standard treatment for
      CA, especially in children and immunodeficient individuals. We report the case of
      a 15-year-old immunocompromised girl with severe recalcitrant condyloma that
      resolved after a course of systemic 5-fluorouracil, mitomycin C, and radiation
      therapy for SCC. 

PMID- 25940811
TI  - Safety of Novel Amino-5-laevulinate Photosensitizer Precursors in Photodynamic
      Therapy for Healthy Human Skin.

PMID- 25940812
TI  - An unusual case of left renal artery compression: a rare type of median arcuate
      ligament syndrome.
AB  - Compression from median arcuate ligament was observed during multidetector 64-row
      computed tomography in a Caucasian 30-year-old female. The patient was referred
      for examination to exclude anatomical pathologies causing hypertension. The
      examination demonstrated that left renal artery, which had its origin in the
      chest (at the level of upper one-third of Th12), was compressed as it passed by
      median arcuate ligament of the diaphragm. In addition, aortic compression and
      kinked shape was also revealed. 

PMID- 25940813
TI  - Assessment and classification of cystic arteries with 64-detector row computed
      tomography before laparoscopic cholecystectomy.
AB  - PURPOSE: Major complications of laparoscopic cholecystectomy are bleeding and
      bile duct injury, and it is necessary to clearly identify structures
      endoscopically to keep bleeding and injury from occurring. The aim of this study
      was to depict the anatomical variation between cystic arteries among patients
      using 64-detector row spiral computed tomography (CT) prior to laparoscopic
      cholecystectomy. METHODS: A total of 78 patients (31 men, 47 women) who underwent
      cholecystectomy were examined preoperatively using 64-detector row spiral CT
      between April 2012 and June 2013. The origin and number of cystic arteries and
      their relationship with the Calot triangle was evaluated by two independent
      observers. CT images were compared with laparoscopic cholecystectomy results.
      RESULTS: The cystic arteries were delineated by CT in 73 of the 78 patients. The
      relationship between the cystic arteries and the Calot triangle was identified in
      71 of the 78 patients. One cystic artery was found in 53 (73%) of the 73
      patients, while two cystic arteries were found in 20 (27%) of the patients. A
      total of 55 (60%) of the 91 cystic arteries passed through the Calot triangle.
      The remaining 36 cystic arteries (40%) passed anterior, posterior, or inferior to
      the cystic duct. The relationship between the cystic arteries and the Calot
      triangle detected by CT was in agreement with the surgical records for all
      patients. CONCLUSION: The configuration of the cystic arteries and their
      relationship with the Calot triangle can be identified using 64-detector row CT
      before laparoscopic cholecystectomy.

PMID- 25940814
TI  - Mapping the quadriceps tendon: an anatomic and morphometric study to guide tendon
      harvesting.
AB  - INTRODUCTION: The quadriceps tendon (QT) may be used in first-line knee ligament
      surgery (Anterior and Posterior Cruciate Ligaments), surgical revision and
      multiligament surgery. There are few published anatomic guides to QT harvesting.
      The present anatomic study sought to determine the ideal harvesting site and exa
      mined possible correlation between patellar and graft sizes. MATERIALS AND
      METHODS: A descriptive morphometric anatomic study was performed on 12 cadaveric
      knees. The reference anatomical landmark was the center of the superior edge of
      the patella. The QT was dissected and sliced longitudinally into five 5-mm
      strips. The central strip corresponded to the anatomic center of the patella. QT
      thickness was measured every 10 mm over a length of 100 mm. Data were analyzed on
      Pearson correlation test and Student, Bartlett and Fisher tests (alpha risk =
      0.05). RESULTS: QT thickness ranged from 0.7 to 9.78 mm, for a mean 4.94 mm. Mean
      thickness in the lateral, central and medial strips was, respectively, 3.464,
      6.040 and 3.899 mm. Central and centromedial strips were thicker than medial,
      centrolateral and lateral strips; central and centromedial strips were similar
      at, respectively, 6.040 and 6.041 mm (non-significant: p = 0.95), and
      significantly thicker than lateral strips. QT thickness showed significant
      correlation with patellar length (r = 0.75; p = 0.0048; 95% CI [+0.31; +0.93]).
      CONCLUSION: The present anatomical study confirmed that QT should be harvested
      from the central and centromedial regions. Mean thickness was 7.84 mm at the
      patellar insertion, 7.37 mm at 20 mm from the insertion, 6.41 at 40 mm, 5.61 at
      60 mm and 4.33 at 100 mm.

PMID- 25940815
TI  - Impact of opioid substitution therapy for Scotland's prisoners on drug-related
      deaths soon after prisoner release.
AB  - AIM: To assess whether the introduction of a prison-based opioid substitution
      therapy (OST) policy was associated with a reduction in drug-related deaths (DRD)
      within 14 days after prison release. DESIGN: Linkage of Scotland's prisoner
      database with death registrations to compare periods before (1996-2002) and after
      (2003-07) prison-based OST was introduced. SETTING: All Scottish prisons.
      PARTICIPANTS: People released from prison between 1 January 1996 and 8 October
      2007 following an imprisonment of at least 14 days and at least 14 weeks after
      the preceding qualifying release. MEASUREMENTS: Risk of DRD in the 12 weeks
      following release; percentage of these DRDs which occurred during the first 14
      days. FINDINGS: Before prison-based OST (1996-2002), 305 DRDs occurred in the 12
      weeks after 80 200 qualifying releases, 3.8 per 1000 releases [95% confidence
      interval (CI) = 3.4-4.2]; of these, 175 (57%) occurred in the first 14 days.
      After the introduction of prison-based OST (2003-07), 154 DRDs occurred in the 12
      weeks after 70 317 qualifying releases, a significantly reduced rate of 2.2 per
      1000 releases (95% CI = 1.8-2.5). However, there was no change in the proportion
      which occurred in the first 14 days, either for all DRDs (87: 56%) or for opioid
      related DRDs. CONCLUSIONS: Following the introduction of a prison-based opioid
      substitution therapy (OST) policy in Scotland, the rate of drug-related deaths in
      the 12 weeks following release fell by two-fifths. However, the proportion of
      deaths that occurred in the first 14 days did not change appreciably, suggesting
      that in-prison OST does not reduce early deaths after release.

PMID- 25940816
TI  - Comparison of phenotypic tests for detecting penicillin G resistance with
      presence of blaZ gene in Staphylococcus aureus isolated from bovine intramammary
      infections.
AB  - Few studies have described the relationship between genotypic and phenotypic
      methods for detecting penicillin resistance in Staphylococcus aureus isolated
      from bovine intramammary infection (IMI). Six phenotypic methods for
      penicillinase detection were compared with a genotypic method testing the
      presence of the beta-lactamase gene blaZ in Staph. aureus (n = 150) isolated from
      bovine IMI. Highest sensitivities and specificities were observed for disk
      diffusion (DD) (93 and 97.4%), minimum inhibitory concentration (MIC) (90.3 and
      97.4%), CefinaseTM (85.9 and 97.4%) and DiatabsTM (85.7 and 98.7%). The estimated
      cut-off points estimated in the present study can be considered close to the ones
      indicated by CLSI (2013). The molecular detection of blaZ gene is the only method
      that may indicate the real or potential capacity of producing beta-lactamase in
      Staph. aureus. Considering that from a clinical standpoint a false negative
      result from a phenotypic test is the most unfavourable situation, a combination
      of standard DD with DiatabsTM or CefinaseTM should be performed by routine
      mastitis laboratories to minimise false negative results.

PMID- 25940817
TI  - Chloride triggered reversible switching from a metallosupramolecular [Pd2L4](4+)
      cage to a [Pd2L2Cl4] metallo-macrocycle with release of endo- and exo-hedrally
      bound guests.
AB  - A metallosupramolecular [Pd2L4](4+) cage can be cleanly converted into a
      [Pd2L2Cl4] metallo-macrocycle upon addition of chloride ions. The process is
      reversible, treatment of the [Pd2L2Cl4] macrocycle with silver(I) ions
      regenerates the [Pd2L4](4+) cage. Additionally, it is shown that guest molecules
      could be released on chloride triggered cage dis-assembly and taken up anew on re
      assembly.

PMID- 25940818
TI  - Multiple Delta11-desaturase genes selectively used for sex pheromone biosynthesis
      are conserved in Ostrinia moth genomes.
AB  - Regulation of the expression of fatty acyl-CoA desaturases, which introduce a
      double bond into the fatty acid moiety of the substrate, is crucial for the
      production of species-specific sex pheromones in moths. In Ostrinia moths, two
      distinct Delta11-desaturases and a Delta14-desaturase are known to be selectively
      used in the biosynthesis of sex pheromones. Of the two Delta11-desaturases, one
      identified from Ostrinia nubilalis and Ostrinia scapulalis, Z/EDelta11, forms the
      Z and E isomers of a double bond at position 11, whereas the other identified
      from Ostrinia latipennis, LATPG1(=EDelta11), exclusively forms an E double bond
      at position 11. Since the retroposon(ezi)-fused, non-functional Delta11
      desaturase gene, ezi-Delta11alpha, in the genomes of O. nubilalis and O.
      furnacalis was previously suggested to be an orthologue of latpg1, we here
      explored Z/EDelta11 orthologues in the genome of O. latipennis. We newly
      identified two Delta11-desaturase genes, latpg2 and latpg3, which were
      orthologous to ezi-Delta11beta and Z/EDelta11, respectively. We found that an ezi
      like element was integrated in intron 1 of latpg1, and confirmed that only latpg1
      was expressed in the pheromone gland of O. latipennis. Thus, at least three
      Delta11-desaturase genes are present in the genome of O. latipennis, and latpg1
      is selectively transcribed in the pheromone gland of this moth. The non
      functionality of ezi-inserted desaturase genes in O. nubilalis and O. furnacalis
      may not be a direct consequence of the insertion of an ezi- or ezi-like element
      into the gene. 

PMID- 25940819
TI  - KIR3DL1 and KIR3DL2 gene copy number variation in axial spondyloarthritis.

PMID- 25940820
TI  - A novel HLA-A allele, HLA-A*02:544.
AB  - The novel allele HLA-A*02:544 has two nucleotide changes from its most closely
      related allele, HLA-A*02:148. Firstly at nucleotide 255 where C -> T (codon 60
      GAC -> GAT), resulting in a non-coding change as GAC and GAT both code for the
      same amino acid aspartic acid. Secondly at nucleotide 368 where T -> G (codon 98
      TTT -> TGT) resulting in a coding change, 98 phenylalanine is changed to
      cysteine. 

PMID- 25940821
TI  - Identification of a novel HLA-DQB1 allele, HLA-DQB1*06:148, by sequence-based
      typing in a Chinese individual.
AB  - One nucleotide replacement in codon 13 (GGC>GCC) of HLA-DQB1*06: 03:01 results in
      a novel allele formation, HLA-DQB1*06:148. 

PMID- 25940822
TI  - Site-specific modification of the 6-amino group of adenosine in RNA by an
      interstrand functionality-transfer reaction with an s-functionalized 4
      thiothymidine.
AB  - Non-natural RNA modifications have been widely used to study the function and
      structure of RNA. Expanding the study of RNA further requires versatile and
      efficient tools for site-specific RNA modification. We recently established a new
      strategy for the site-specific modification of RNA based on a functionality
      transfer reaction between an oligodeoxynucleotide (ODN) probe and an RNA
      substrate. 2'-Deoxy-6-thioguanosine was used to anchor the transfer group, and
      the 4-amino group of cytosine or the 2-amino group of guanine was specifically
      modified. In this study, 2'-deoxy-4-thiothymidine was adopted as a new platform
      to target the 6-amino group of adenosine. The (E)-pyridinyl vinyl keto transfer
      group was attached to the 4-thioT in the ODN probe, and it was efficiently and
      specifically transferred to the 6-amino group of the opposing adenosine in RNA in
      the presence of CuCl2 . This method expands the available RNA target sites for
      specific modification.

PMID- 25940824
TI  - Therapeutic drug monitoring and pharmacokinetics/pharmacodynamics of antibiotics
      as useful tools for translational research and personalized medicine.

PMID- 25940823
TI  - Effects of Pharmacogenetics on the Pharmacokinetics and Pharmacodynamics of
      Tamoxifen.
AB  - The antiestrogenic drug tamoxifen is widely used in the treatment of estrogen
      receptor-alpha-positive breast cancer and substantially decreases recurrence and
      mortality rates. However, high interindividual variability in response is
      observed, calling for a personalized approach to tamoxifen treatment. Tamoxifen
      is bioactivated by cytochrome P450 (CYP) enzymes such as CYP2B6, CYP2C9, CYP2C19,
      CYP2D6 and CYP3A4/5, resulting in the formation of active metabolites, including
      4-hydroxy-tamoxifen and endoxifen. Therefore, polymorphisms in the genes encoding
      these enzymes are proposed to influence tamoxifen and active tamoxifen
      metabolites in the serum and consequently affect patient response rates. To
      tailor tamoxifen treatment, multiple studies have been performed to clarify the
      influence of polymorphisms on its pharmacokinetics and pharmacodynamics.
      Nevertheless, personalized treatment of tamoxifen based on genotyping has not yet
      met consensus. This article critically reviews the published data on the effect
      of various genetic polymorphisms on the pharmacokinetics and pharmacodynamics of
      tamoxifen, and reviews the clinical implications of its findings. For each CYP
      enzyme, the influence of polymorphisms on pharmacokinetic and pharmacodynamic
      outcome measures is described throughout this review. No clear effects on
      pharmacokinetics and pharmacodynamics were seen for various polymorphisms in the
      CYP encoding genes CYP2B6, CYP2C9, CYP2C19 and CYP3A4/5. For CYP2D6, there was a
      clear gene-exposure effect that was able to partially explain the interindividual
      variability in plasma concentrations of the pharmacologically most active
      metabolite endoxifen; however, a clear exposure-response effect remained
      controversial. These controversial findings and the partial contribution of
      genotype in explaining interindividual variability in plasma concentrations of,
      in particular, endoxifen, imply that tailored tamoxifen treatment may not be
      fully realized through pharmacogenetics of metabolizing enzymes alone. 

PMID- 25940825
TI  - Prediction of Fat-Free Mass in Children.
AB  - BACKGROUND: Fat-free mass (FFM) is an important covariate for predicting drug
      clearance. Models for predicting FFM have been developed in adults but there is
      currently a paucity of mechanism-based models developed to predict FFM in
      children. OBJECTIVE: The aim of this study was to develop and evaluate a model to
      predict FFM in children. METHODS: A large dataset (496 females and 515 males) was
      available for model building. Subjects had a relatively wide range of age (3-29
      years) and body mass index values (12-44.9 kg/m(2)). Two types of models (M1 and
      M2) were developed to describe FFM in children. M1 was fully empirical and based
      on a linear model that contained all statistically significant covariates and
      their interactions. M2 was a simpler model that incorporated a maturation
      process. M1 was developed to provide the best possible description of the data
      (i.e. a positive control). In addition, a published adult model (M3) was applied
      directly as a reference description of the data. The predictive performances of
      the three models were assessed by visual predictive checks and by using mean
      error (ME) and root mean squared error (RMSE). A test dataset (90 females and 86
      males) was available for external evaluation. RESULTS: M1 consisted of nine terms
      with up to second-level interactions. M2 was a sigmoid hyperbolic model based on
      postnatal age with an asymptote at the adult prediction (M3). For the index
      dataset, the ME and 95 % CI for M1, M2 and M3 were 0.09 (0.03-0.16), 0.24 (0.14
      0.33) and 0.29 (0.06-0.51) kg, respectively, and RMSEs were 1.12 (1.03-1.23),
      1.58 (1.46-1.72) and 3.76 (3.54-3.97) kg. CONCLUSIONS: A maturation model that
      asymptoted to an established adult model was developed for prediction of FFM in
      children. This model was found to perform well in both male and female children;
      however, the adult model performed similarly to the maturation model for females.
      The ability to predict FFM in children from simple demographic measurements is
      expected to improve understanding of human body structure and function with
      direct application to pharmacokinetics.

PMID- 25940826
TI  - Population Pharmacokinetic/Pharmacodynamic Modelling of Dipeptidyl Peptidase IV
      Inhibitors.

PMID- 25940827
TI  - A critical review on the clinical pharmacokinetics, pharmacodynamics, and
      clinical trials of ceftaroline.
AB  - Only a parenteral formulation of ceftaroline is commercially available, and the
      prodrug, ceftaroline fosamil, is hydrolyzed quickly and completely upon
      intravenous administration. Ceftaroline is relatively minimally bound to plasma
      proteins (15-28 %), with a volume of distribution of 30-40 L. Ceftaroline
      undergoes minimal metabolism and does not appear to be a cytochrome P450
      substrate. Its renal clearance (e.g. 4-7 L/h after multiple dosing) approximates
      glomerular filtration rate, with a terminal half-life of ~2.6 h in healthy
      subjects. The pharmacokinetics of ceftaroline have been described thoroughly in
      clinical investigations primarily conducted by the manufacturer. Despite its
      indications for treating skin and skin structure infections (SSSI) or community
      acquired pneumonia (CAP), some studies that contributed data to the final drug
      labelling were conducted only in healthy volunteers. A significant amount of data
      have been contributed by the drug maker, and the overall quality of the
      pharmacodynamics and clinical data, based on our critical analysis provided in
      this review, is strong. Ceftaroline can be considered as a therapeutic
      alternative for complicated SSSI and CAP (Pneumonia Outcome Research Team Class
      III-IV). The current dosing regimen of ceftaroline 600 mg intravenously every 12
      h appears sufficient to establish pharmacokinetic-pharmacodynamic relationships
      and achieve optimal clinical efficacy. More clinical studies are needed to define
      the place of ceftaroline in therapy for SSSI, CAP, and other indications such as
      osteomyelitis, endocarditis, and other types of pneumonia. Moreover, continued
      development in population modelling incorporating more patient-specific data
      would allow further analysis to identify intrinsic and extrinsic factors that
      influence the pharmacokinetics of ceftaroline in humans. 

PMID- 25940828
TI  - Top 10 food allergy myths.

PMID- 25940829
TI  - Effect of fructose 1,6-bisphosphate on the iron redox state relating to the
      generation of reactive oxygen species.
AB  - Role of fructose 1,6-bisphosphate-mediated iron oxidation in the generation of
      reactive oxygen species was analyzed. Aconitase the most sensitive enzyme to
      oxidative stress was inactivated potently by fructose 1,6-bisphosphate in the
      presence of ferrous ion, and further by ADP and PEP to a lesser extent. The
      inactivation requires cyanide, suggesting that the superoxide radical is
      responsible for the inactivation. Addition of ascorbic acid and dithiothreitol
      prevented aconitase from the inactivation. Fructose 1,6-bisphosphate, ADP and PEP
      stimulated the oxidation of ferrous ion causing one-electron reduction of oxygen
      molecule. Superoxide radical formed with iron oxidation participates in the
      oxidative inactivation of aconitase and the citric acid cycle, resulting in the
      induction of the Crabtree effect, that is, high glucose-mediated inhibition of
      oxidative metabolism in mitochondria. 

PMID- 25940830
TI  - Alterations in zinc binding capacity, free zinc levels and total serum zinc in a
      porcine model of sepsis.
AB  - Zinc is crucial for immune function. In addition, the redistribution of zinc and
      other nutrients due to infection is an integral part of the host immune response
      to limit availability to pathogens. However, the major zinc binding protein
      albumin is down regulated during the acute phase response, implicating a decrease
      in zinc binding capacity. A prospective animal study with eight female German
      landrace pigs was conducted to investigate alterations in zinc binding capacity,
      total serum zinc and free zinc levels in the initial phase of sepsis. Sepsis was
      induced by instillation of autologous feces via midline laparotomy. Total serum
      zinc declined significantly after 1 h (10.89 +/- 0.42 uM vs. 7.67 +/- 0.41 uM, p
      < 0.001), total serum copper and iron reached a significant reduction at 4 h.
      Urinary excretion of zinc declined in line with total serum zinc. In comparison
      to total serum zinc, free zinc levels declined to a lesser, though significant,
      extent. Zinc binding capacity of serum decreased over time, whereby free zinc
      levels after addition of zinc correlated negatively with total serum protein and
      albumin levels. In addition IL-6 and TNF-alpha concentrations were measured and
      increased significantly 2 h after induction of sepsis. Hence, total serum zinc
      was the first marker of inflammation in our experiment, and might therefore be a
      promising biomarker for the early diagnosis of sepsis. Furthermore the
      observation of a substantially different serum free zinc homeostasis during
      sepsis provides valuable information for a potential therapeutic zinc
      supplementation, which has to take buffering capacity by serum proteins into
      account.

PMID- 25940831
TI  - Low incidence of pulmonary aspiration in children allowed intake of clear fluids
      until called to the operating suite.
AB  - BACKGROUND: International guidelines recommend 2 h of clear fluid fasting prior
      to general anesthesia. The pediatric anesthesia unit of Uppsala University
      Hospital has been implementing a more liberal fasting regime for more than a
      decade; thus, children scheduled for elective procedures are allowed to drink
      clear fluids until called to the operating suite. AIM: To determine the incidence
      of perioperative pulmonary aspiration in pediatric patients allowed unlimited
      intake of clear fluids prior to general anesthesia. METHOD: Elective pediatric
      procedures between January 2008 and December 2013 were examined retrospectively
      by reviewing anesthesia charts and discharge notes in the electronic medical
      record system. All notes from the care event and available chest x-rays were
      examined for cases showing vomiting, regurgitation, and/or aspiration. Pulmonary
      aspiration was defined as radiological findings consistent with aspiration and/or
      postoperative symptoms of respiratory distress after vomiting during anesthesia.
      RESULTS: Of the 10,015 pediatric anesthetics included, aspiration occurred in
      three (0.03% or 3 in 10,000) cases. No case required cancellation of the surgical
      procedure, intensive care or ventilation support, and no deaths attributable to
      aspiration were found. Pulmonary aspiration was suspected, but not confirmed by
      radiology or continuing symptoms, in an additional 14 cases. CONCLUSION:
      Shortened fasting times may improve the perioperative experience for parents and
      children with a low risk of aspiration.

PMID- 25940832
TI  - DYNAMERS: dynamic polymers as self-healing materials.
AB  - Importing self-repair or self-healing features into inert materials is of great
      relevance to material scientists, since it is expected to eliminate the necessity
      of replenishing a damaged material. Be it material chemistry or more specifically
      polymer chemistry, such materials have attracted the imagination of both material
      scientists and chemists. A stroll down the memory lane 70 years back, this might
      have sounded utopian. However with the current progress in supramolecular
      chemistry and the emergence of dynamic covalent and non-covalent chemistries,
      novel perspectives have been opened up to materials science towards the
      development of dynamic materials (DYNAMATS) and in particular dynamic polymers
      (DYNAMERS), with the ability to produce such species by custom made designs.
      Chemistry took giant strides to gain control over the structure and features of
      materials and, besides basic progress, to apply it for tailor-making matter for
      applications in our daily life. In that applied perspective, materials science
      plays a paramount role in shaping our present and in contributing to a
      sustainable future. The goal is to develop materials, which would be dynamic
      enough to carry out certain functions as effectively as in biological systems
      with, however, the freedom to recruit the powers of chemistry on a wider scale,
      without the limitation imposed by life. Material scientists and in particular
      polymer chemists may build on chemistry, physics and biology for bridging the gap
      to develop dynamic materials presenting a wide range of novel functionalities and
      to convert dreams into reality. In this current review we will focus on
      developments in the area of dynamic polymers, as a class of dynamic materials
      presenting self-healing features and, more generally, the ability to undergo
      adaptation under the effect of physical and/or chemical agents, and thus function
      as adaptive polymers or ADAPTAMERS. 

PMID- 25940833
TI  - Enantioselective separation and determination of the dinotefuran enantiomers in
      rice, tomato and apple by HPLC.
AB  - An effective chiral analytical method was developed for the resolution and
      determination of dinotefuran enantiomers in rice, tomato and apple samples.
      Dinotefuran enantiomers were baseline-separated and determined on a novel chiral
      column, ChromegaChiral CCA, with n-hexane-ethanol-methanol (85:5:10, v/v/v) as
      the mobile phase at a flow rate of 1.0 mL/min with UV detection at 270 nm. The
      resolution of dinotefuran enantiomers was about 1.8. The first eluted enantiomer
      was (+)-dinotefuran and the second eluted one was (-)-dinotefuran. The effects of
      mobile-phase composition and column temperature on the enantioseparation were
      evaluated. The method was validated for linearity, repeatability, accuracy, LOD
      and LOQ. LOD was 0.15 mg/kg in rice and tomato, 0.05 mg/kg in apple, with an LOQ
      of 0.5 mg/kg in rice and tomato, 0.2 mg/kg in apple. The average recoveries of
      the pesticide from all matrices ranged from 75.8 to 92.9% for all fortification
      levels The precision values associated with the analytical method, expressed as
      RSD values, were <16.5% for the pesticide in all matrices. The methodology was
      successfully applied for the enantioselective analysis of dinotefuran enantiomers
      in real samples, indicating its efficiency in investigating the environmental
      stereochemistry of dinotefuran in food matrix. 

PMID- 25940834
TI  - Melperone but not bisoprolol or metoprolol is a clinically relevant inhibitor of
      CYP2D6: evidence from a therapeutic drug monitoring survey.
AB  - Cytochrome P450 enzymes (CYP) can be inhibited or induced by drugs, resulting in
      clinically significant drug-drug interactions that can cause unanticipated
      adverse reactions or therapeutic failures. The objective of the study was to
      analyze the in vivo inhibitory potential of the beta-blockers bisoprolol and
      metoprolol as well as the low-potency antipsychotic melperone on CYP2D6. By
      utilizing a large therapeutic drug monitoring database of 2874 samples, data from
      patients who had been treated with venlafaxine (VEN) either without (control
      group) or with a concomitant medication with bisoprolol, metoprolol or melperone
      were evaluated retrospectively to study the CYP2D6-catalyzed O-demethylation to O
      desmethylvenlafaxine (ODVEN). Dose-adjusted serum levels (C/D) of VEN and ODVEN
      as well as the metabolic ratios (ODVEN/VEN) were computed for the four groups and
      compared using Kruskal-Wallis test. In total, 381 patients could be included for
      analysis. No significant difference was found in the median C/D (VEN), C/D
      (ODVEN) or C/D of the active moiety (VEN + ODVEN) in either the metoprolol (N =
      103) or bisoprolol group (N = 101), compared to the control group (N = 108). In
      contrast, a significantly higher median C/D (VEN) (0.79 ng/ml/mg, range 0.13-5.73
      ng/ml/mg) (P < 0.01) was found in the melperone group (N = 69), compared to the
      control group (0.46 ng/ml/mg, range 0.02-7.39 ng/ml/mg). A significant decrease
      (P < 0.01) was solely found in the median metabolic ratios of ODVEN/VEN between
      the melperone group (0.90, range 0.14-15.15), compared to the control group
      (2.39, range 0.06-15.31). The results of this study provided evidence that
      melperone but not bisoprolol or metoprolol has a clinically relevant inhibitory
      potential on CYP2D6. 

PMID- 25940835
TI  - Water-resistant sunscreens for skin protection: an in vivo approach to the two
      sources of sunscreen failure to maintain UV protection on consumer skin.
AB  - OBJECTIVES: The water resistance of sunscreen products has taken more importance
      for the UV protection of consumers involved in water activities and sports. The
      present work introduces a new in vivo approach to measure the water resistance of
      sunscreens on the actual skin of subjects, which can be easily applied to salt,
      chlorine and tap waters. The stress sources of sunscreen films on skin originate
      from two phenomena: high surface tension stress as the skin transits through the
      air/water interface and water diffusion into the film immersed in bulk water.
      METHODS: The water resistance of sunscreen products is measured on the forearms
      of subjects by means of a new layered water bath approach that physically
      separates both stresses. Tape strips are subsequently taken and analysed for UV-A
      and UV-B optical densities via (1) imaging for remaining filters and (2) in vitro
      SPF absorption spectra. RESULTS: Water-resistant sunscreens generally perform
      well when immersed in bulk water even subjected to agitation, but they show a
      wide range of performances when considering their behaviour at the air/water
      interface. The differences are more pronounced in salt water than tap water.
      CONCLUSIONS: The results confirm 2 stress origins in sunscreen exposure to water:
      interfacial surface tension and bulk water diffusion. Polymers bring improvements
      to the resistance of sunscreens to bulk water but show wide latitude in
      performances when subject to the water surface tension stress. Globally, a higher
      loss of filters is observed in the UV-A than in the UV-B, which is attributed to
      more UV-A filter loss or degradation and thus resulting in a decreased protection
      in the UV-A.

PMID- 25940836
TI  - Computational Modeling of Neonatal Cardiopulmonary Bypass Hemodynamics With Full
      Circle of Willis Anatomy.
AB  - Cardiopulmonary bypass (CPB) procedure is employed to repair most congenital
      heart defects (CHD). Cannulation is a critical component of this procedure where
      the location and diameter of cannula controls the hemodynamic performance. State
      of-the-art computational studies of neonatal CPB employed an isolated aortic arch
      region by truncating the three-dimensional (3D) patient-specific cerebral system.
      The present work expanded these studies where the 3D patient-specific MRI
      reconstruction of the cerebral system, including the Circle of Willis (CoW), is
      integrated with a hypoplastic neonatal aortic arch. The inlet of the arterial
      cannula is assigned a steady velocity boundary condition of the CPB pump, while
      all outlets are modeled as resistance boundary conditions, thus allowing acute
      comparisons between different cannula configurations. Three-dimensional (3D) flow
      simulations in the aortic arch model are performed at a Reynolds number of 2150
      using an experimentally validated commercial solver. Results demonstrate that the
      inclusion of 3D CoW is essential to predict the accurate head-neck blood
      perfusion and therefore critical in deciding the neonatal aortic cannulation
      strategy preoperatively. Using this integrated model two CPB configurations are
      studied, where the cannulas were placed at innominate artery (IA) (IA-cannula
      configuration) and ductus arteriosus (DA) (DA-cannula configuration).
      Configuration change produced significant differences in flow splits and local
      hemodynamics of blood flow throughout the whole aortic arch, neck and cerebral
      arteries. Percent flow rate differences between the IA- and DA-cannula
      configurations are computed to be: 19%, for descending aorta, 198% for ascending
      aorta (perfusing coronary arteries), 91% for right anterior cerebral artery, and
      68% for left anterior cerebral artery. Another important finding is the
      retrograde flow at vertebral arteries for IA-cannula configuration, but not for
      DA-cannula. These results may help to translate better neonatal arterial cannulae
      design for minimizing cerebral complications during CPB procedures.

PMID- 25940837
TI  - Cyclic fatigue of two different single files with varying kinematics in a
      simulated double-curved canal.
AB  - OBJECTIVE: To evaluate and compare the cyclic fatigue of a rotary (One Shape) and
      reciprocating (Reciproc) single file system in a simulated S-shaped canal in
      static and dynamic models. METHODS: The instruments (n = 50 per instrument) were
      tested in a custom-made device under static (n = 25) and dynamic loads (n = 25)
      to determine the number of cycles to fracture (NCF). The length of the fractured
      segments was also measured. Cyclic fatigue data were analyzed by one-way analysis
      of variance and Tukey honestly significantly different tests, while the data
      recorded for the fractured fragment lengths were compared using Student's t-test
      with the level of significance set at 0.05. RESULTS: The fatigue life of Reciproc
      was significantly higher in the static (coronal curvature: 717.60 +/- 45.32 NCF;
      apical curvature: 621.80 +/- 60.15 NCF) and dynamic models (coronal curvature:
      972.40 +/- 54.30 NCF, apical curvature: 897.70 +/- 47.10 NCF) as compared with
      One Shape (P < 0.05). The fatigue life was significantly prolonged in the dynamic
      model for Reciproc (P < 0.05) as compared to One Shape (P > 0.05). CONCLUSION:
      The results of the present study showed that the single file reciprocating system
      (Reciproc) had a longer fatigue life than the single file rotary system (One
      Shape).

PMID- 25940838
TI  - HSF4 promotes G1/S arrest in human lens epithelial cells by stabilizing p53.
AB  - The differentiation from constantly dividing epithelial cells into secondary
      fiber cells is a key step during lens development. Failure in this process, which
      requires cell proliferation inhibition and cell cycle exit, causes cataract
      formation. HSF4 (Heat Shock Transcription Factor 4) gene mutations may lead to
      both congenital and senile cataract. However, how HSF4 mutations induce cataract
      formation remains obscure. In this study, we demonstrate that HSF4 can suppress
      the proliferation of human lens epithelial cells (HLECs) by promoting G1/S arrest
      in a p53-dependent manner. In contrast, HSF4 with cataract causative mutations
      fail to cause cell cycle arrest and have no obvious effect on cell proliferation.
      We further identify that HSF4 recruits p53 in the nucleus and promotes its
      transcriptional activity, leading to the expression of its target gene p21 in
      HLECs. HSF4, but not its cataract-causing mutants, stabilizes p53 protein and
      inhibits its ubiquitin degradation. Our data reveal that HSF4 may work as a
      switch between lens epithelial cell proliferation and secondary fiber cell
      differentiation, a process which mainly depends on p53. Through demonstration of
      this novel downstream pathway of HSF4, our results help uncover the pathogenic
      mechanisms caused by HSF4 mutations.

PMID- 25940839
TI  - Fast and bright spontaneous emission of Er(3+) ions in metallic nanocavity.
AB  - By confining light in a small cavity, the spontaneous emission rate of an emitter
      can be controlled via the Purcell effect. However, while Purcell factors as large
      as ~10,000 have been predicted, actual reported values were in the range of about
      10-30 only, leaving a huge gap between theory and experiment. Here we report on
      enhanced 1.54-MUm emission from Er(3+) ions placed in a very small metallic
      cavity. Using a cavity designed to enhance the overall Purcell effect instead of
      a particular component, and by systematically investigating its photonic
      properties, we demonstrate an unambiguous Purcell factor that is as high as 170
      at room temperature. We also observe >90 times increase in the far-field radiant
      flux, indicating that as much as 55% of electromagnetic energy that was initially
      supplied to Er(3+) ions in the cavity escape safely into the free space in just
      one to two optical cycles. 

PMID- 25940840
TI  - Physical Activity Levels Among Adolescent and Young Adult Women and Men with and
      without Intellectual Disability.
AB  - BACKGROUND: As physical activity can prevent overweight and promote general
      health, the aim was to investigate the amount of physical activity among
      adolescent and young adult women and men with intellectual disability (ID),
      compared to age-matched control groups without intellectual disability. A further
      aim was to examine whether physical activity level was associated with the body
      mass index (BMI). MATERIALS AND METHODS: Fifty-two adolescent and young adult
      women and men with intellectual disability and 48 without intellectual
      disability, between the ages 16 and 20 years, BMIs ranging from 16.3 to 50.3
      kg/m(2) , were measured for number of steps taken with a pedometer for five
      consecutive days (Sunday-Thursday). RESULTS: The only group to meet
      recommendations regarding number of steps (10 000-12 000/day) was women without
      intellectual disability. No significant associations were found between total
      number of steps taken and BMI. CONCLUSION: As the majority of adolescents and
      young adults with intellectual disability, especially women, did not reach
      recommended activity levels regardless of their BMIs, this call for broad
      measures to increase physical activity.

PMID- 25940841
TI  - Improved determination of uracil and dihydrouracil in plasma after a loading oral
      dose of uracil using high-performance liquid chromatography with photodiode array
      detection and porous graphitic carbon stationary phase.
AB  - OBJECTIVES: The aim of this study was to develop and validate a high-performance
      liquid chromatographic method for the measurement of plasma concentrations of
      uracil and dihydrouracil after administration of an oral loading dose of uracil
      in the context of evaluation of DPD enzyme activity. DESIGN AND METHODS: Analytes
      were extracted from 500MUL plasma sampler with a mixture of ethyl acetate
      isopropanol (85:15, v/v) after protein precipitation with solid ammonium sulfate.
      The extract was inject in the porous graphitic carbon stationary phase, eluted
      with water and acetonitrile in gradient mode, allowing complete separation of
      uracil, dihydrouracil and the internal standard (5-fluorouracil). Chromatograms
      were monitored at 210 and 260nm. RESULTS: Total chromatographic run time,
      including reequilibration, was 30min. The assay was linear in the concentration
      range of 0.2 to 20MUgmL(-1). Accuracy was 98.4-105.3%, intra-assay precision was
      5.1-12.1% and between-assay precision was of 5.3-10.1%. Analytes were stable in
      plasma at room temperature up to 6h and for three freeze and thaw cycles.
      Processed samples are stable up to 12h. CONCLUSIONS: The developed method was
      fully validated and has significantly reduced running time when compared to
      previous assay using porous graphitic stationary phase, allowing complete
      resolution of uracil, dihydrouracil and internal standard. This assay might be
      suitable to investigate the eventual correlation between concentrations of uracil
      and dihydrouracil in plasma after an oral loading dose and DPD enzyme activity,
      with potential contribution to therapeutic drug monitoring.

PMID- 25940842
TI  - Fighting Sleep at Night: Brain Correlates and Vulnerability to Sleep Loss.
AB  - OBJECTIVE: Even though wakefulness at night leads to profound performance
      deterioration and is regularly experienced by shift workers, its cerebral
      correlates remain virtually unexplored. METHODS: We assessed brain activity in
      young healthy adults during a vigilant attention task under high and low sleep
      pressure during night-time, coinciding with strongest circadian sleep drive. We
      examined sleep-loss-related attentional vulnerability by considering a PERIOD3
      polymorphism presumably impacting on sleep homeostasis. RESULTS: Our results link
      higher sleep-loss-related attentional vulnerability to cortical and subcortical
      deactivation patterns during slow reaction times (i.e., suboptimal vigilant
      attention). Concomitantly, thalamic regions were progressively less recruited
      with time-on-task and functionally less connected to task-related and arousal
      promoting brain regions in those volunteers showing higher attentional
      instability in their behavior. The data further suggest that the latter is linked
      to shifts into a task-inactive default-mode network in between task-relevant
      stimulus occurrence. INTERPRETATION: We provide a multifaceted view on cerebral
      correlates of sleep loss at night and propose that genetic predisposition entails
      differential cerebral coping mechanisms, potentially compromising adequate
      performance during night work.

PMID- 25940843
TI  - Southern Hospitality: How We Changed the NPO Practice in the Emergency
      Department.
AB  - PROBLEM: In the Vanderbilt Medical Center adult emergency department, the
      practice has been to keep patients on "nothing by mouth" (NPO) status throughout
      their assessment, diagnostic, and treatment phases. As a result, most patients
      have NPO status for a period of several hours to days. The consequences are
      patient discomfort, hunger, thirst, dehydration, interruptions in routine
      medication schedules, poor glucose control, and compromised acid/base balance.
      The purpose of this project was to modify the NPO practice in the adult emergency
      department. METHODS: A survey of nursing staff perceptions demonstrated both
      staff and patient dissatisfaction with the NPO practice. Responses to
      postdischarge satisfaction surveys demonstrated that patients experienced some
      discomfort because of hunger or thirst. A search of the literature revealed that
      the American Society of Anesthesiologists (ASA) adopted guidelines in 1999 that
      patients should fast 6 hours from solids and 2 hours from liquids preoperatively.
      These guidelines were implemented in the adult emergency department using the
      Standard Rollout Process. Physician order sets for the emergency department and
      the ED chest pain unit were modified to reflect the ASA guidelines. RESULTS:
      After implementation of the ASA guidelines, a follow-up survey of nursing staff
      showed increased staff and patient satisfaction. After implementation, the
      patient satisfaction survey demonstrated an increase in patients who reported "no
      discomfort" because of hunger or thirst. No adverse outcomes or delays were
      reported in relation to the change in NPO standards. This change in practice
      resulted in improved satisfaction for patents and staff. IMPLICATIONS FOR
      PRACTICE: The ASA guidelines have been in existence for more than a decade. They
      are evidence based. The role of the nurse is to advocate for the patient. Nurses
      need to be proactive in determining the timing of procedures and asking
      physicians to give diet orders that are in accordance with the ASA guidelines.

PMID- 25940844
TI  - Purification and functional characterization of diadenosine 5',5'''-P(1),P(4)
      tetraphosphate phosphorylases from Mycobacterium smegmatis and Mycobacterium
      avium.
AB  - We recently demonstrated that the Rv2613c protein from Mycobacterium tuberculosis
      H37Rv is a novel diadenosine 5',5'''-P(1),P(4)-tetraphosphate (Ap4A)
      phosphorylase (MtAPA) that forms a tetramer. Mycobacterium avium and
      Mycobacterium smegmatis express proteins named MAV_3489 and MSMEG_2932,
      respectively, that are homologous to MtAPA. Here we showed that the MAV_3489 and
      MSMEG_2932 proteins possess Ap4A phosphorylase activity and enzymatic properties
      similar to those of MtAPA. Furthermore, gel-filtration column chromatography
      revealed that MAV_3489 and MSMEG_2932 assembled into homotetramers in solution,
      indicating that they may also form unique Ap4A-binding sites composed of
      tetramers. 

PMID- 25940845
TI  - The effect of tissue anisotropy on the radial and tangential components of the
      electric field in transcranial direct current stimulation.
AB  - Transcranial direct current stimulation (tDCS) is considered to be a promising
      technique for noninvasive brain stimulation and brain disease therapy. Recent
      studies have investigated the distribution of the electric field (EF) magnitude
      over gyri and sulci and the effect of tissue homogeneity with isotropic
      electrical conductivities. However, it is well known that the skull and white
      matter (WM) are highly anisotropic electrically, requiring investigations of
      their anisotropic effects on the magnitude and the directional components of the
      induced EF due to the high dependency between neuromodulation and the EF
      direction. In this study, we investigated the effects of the skull and WM
      anisotropy on the radial and tangential components of the EF via gyri-specific
      high-resolution finite element head models. For tDCS, three configurations were
      investigated: the conventional rectangular pad electrode, a 4(cathodes) +1(anode)
      ring configuration, and a bilateral configuration. The results showed that the
      skull anisotropy has a crucial influence on the distribution of the radial EF
      component. The affected cortical regions by the radial EF were reduced about 22 %
      when considering the skull anisotropy in comparison with the regions with the
      skull isotropy. On the other hand, the WM anisotropy strongly alters the EF
      directionality, especially within the sulci. The electric current tends to flow
      radially to the cortical surface with the WM anisotropy. This effect increases
      the affected cortical areas by the radial EF component within the sulcal regions.
      Our results suggest that one must examine the distribution of the EF components
      in tDCS, not just the magnitude of the EF alone. 

PMID- 25940847
TI  - Evolution of sexual dimorphism in phenotypic covariance structure in Phymata.
AB  - Sexual dimorphism is a consequence of both sex-specific selection and potential
      constraints imposed by a shared genetic architecture underlying sexually
      homologous traits. However, genetic architecture is expected to evolve to
      mitigate these constraints, allowing the sexes to approach their respective
      optimal mean phenotype. In addition, sex-specific selection is expected to
      generate sexual dimorphism of trait covariance structure (e.g., the phenotypic
      covariance matrix, P), but previous empirical work has not fully addressed this
      prediction. We compared patterns of phenotypic divergence, for three traits in
      seven taxa in the insect genus Phymata (Reduviidae), to ask whether sexual
      dimorphism in P is common and whether its magnitude relates to the extent of
      sexual dimorphism in trait means. We found that sexual dimorphism in both mean
      and covariance structure was pervasive but also that the multivariate distance
      between sex-specific means was correlated with sex differences in the leading
      eigenvector of P, while accounting for uncertainty in phylogenetic relationships.
      Collectively, our findings suggest that sexual dimorphism in covariance structure
      may be a common but underappreciated feature of dioecious populations. 

PMID- 25940846
TI  - Symbiotic in vitro seed propagation of Dendrobium: fungal and bacterial partners
      and their influence on plant growth and development.
AB  - The genus Dendrobium is one of the largest genera of the Orchidaceae Juss.
      family, although some of its members are the most threatened today. The reason
      why many species face a vulnerable or endangered status is primarily because of
      anthropogenic interference in natural habitats and commercial overexploitation.
      The development and application of modern techniques and strategies directed
      towards in vitro propagation of orchids not only increases their number but also
      provides a viable means to conserve plants in an artificial environment, both in
      vitro and ex vitro, thus providing material for reintroduction. Dendrobium seed
      germination and propagation are challenging processes in vivo and in vitro,
      especially when the extreme specialization of these plants is considered: (1)
      their biotic relationships with pollinators and mycorrhizae; (2) adaptation to
      epiphytic or lithophytic life-styles; (3) fine-scale requirements for an optimal
      combination of nutrients, light, temperature, and pH. This review also aims to
      summarize the available data on symbiotic in vitro Dendrobium seed germination.
      The influence of abiotic factors as well as composition and amounts of different
      exogenous nutrient substances is examined. With a view to better understanding
      how to optimize and control in vitro symbiotic associations, a part of the review
      describes the strong biotic relations of Dendrobium with different associative
      microorganisms that form microbial communities with adult plants, and also
      influence symbiotic seed germination. The beneficial role of plant growth
      promoting bacteria is also discussed. 

PMID- 25940848
TI  - Active Drug Targeting of a Folate-Based Cyclodextrin-Doxorubicin Conjugate and
      the Cytotoxic Effect on Drug-Resistant Mammary Tumor Cells In Vitro.
AB  - Active drug targeting is an effective therapeutic approach for the treatment of
      malignant cancers and novel types of drug carriers have been developed. In this
      study, we developed a cyclodextrin (CD)-based novel carrier-drug conjugate,
      called per-FOL-beta-CD-ss-DOX, which has folic acid (FA) molecules at the end of
      primary hydroxyl groups of beta-CD and a pH-cleavable spacer with an anticancer
      drug, doxorubicin (DOX), at the end of secondary hydroxyl groups. This per-FOL
      beta-CD-ss-DOX exhibited a significant cellular uptake as compared with the free
      DOX solution by EMT6/P cells, which activate the expression of folate receptor
      (FR). Cellular uptake of per-FOL-beta-CD-ss-DOX was significantly inhibited in
      the presence of FA and was also inhibited at 4 degrees C. The conjugate exhibited
      remarkable cytotoxic effects in EMT6/AR1 cells, which are resistant to DOX,
      whereas free DOX solution did not exhibit this effect. These results suggest that
      per-FOL-beta-CD-ss-DOX can be taken up into cells via FR-related endocytosis and
      the cleaved DOX derived from it in endosomes could escape the efflux caused by P
      glycoprotein, resulting in the cytotoxic effect. Therefore, the drug delivery by
      per-FOL-beta-CD-ss-DOX may be a useful approach for drug delivery to FR
      expressing cells such as drug-resistant malignant cancers.

PMID- 25940849
TI  - N-3-Methylbutanoyl-O-methylpropanoyl-L-serine Methyl Ester - Pheromone Component
      of Western Black Widow Females.
AB  - Chemical communication is common in spiders but few pheromones have been
      identified. Female widow spiders in the genus Latrodectus spin webs that
      disseminate an attractive sex pheromone, and a contact pheromone on the silk
      elicits courtship behavior by males. The methyl ester of N-3-methylbutanoyl-O-(S)
      2-methylbutanoyl-L-serine is a contact pheromone of the Australian redback spider
      Latrodectus hasselti. We hypothesized that the contact pheromone of congeneric L.
      hesperus resembles that of L. hasselti. The silk of virgin L. hesperus females
      was extracted with methanol, and analyses by gas chromatography-mass spectrometry
      (GC/MS) provided evidence for the presence of N-3-methylbutanoyl-O
      methylpropanoyl-L-serine methyl ester (MB-MP-S), a lower homologue of the L.
      hasselti contact pheromone. Behavioral responses of L. hesperus males to test
      stimuli were assayed on T-shaped rods with the end sections of the horizontal arm
      enveloped in filter paper. Males spent 40 % longer in contact with paper bearing
      female silk than with blank paper, and 39 % longer in contact with paper treated
      with silk extract than with solvent controls. Contact with silk and silk extract
      induced courtship behavior by 96 % and 80 % of males, respectively, indicating
      that there was a methanol-soluble courtship-eliciting contact pheromone on the
      silk. Males responded less strongly to synthetic MB-MP-S than to silk or silk
      extract. Paper impregnated with synthetic MB-MP-S (10 or 100 MUg) induced
      courtship behavior in 3-16 % of males, and prompted males to stay 10-16 % longer
      than on control paper. Our data support the conclusion that MB-MP-S is part of a
      multi-component contact pheromone of L. hesperus.

PMID- 25940850
TI  - An experimental study on the effects of temperature and magnetic field strength
      on the magnetorheological fluid stability and MR effect.
AB  - In this study, the stability and rheological properties of a suspension of
      carbonyl iron microparticles (CIMs) in silicone oil were investigated within a
      temperature range of 10 to 85  degrees C. The effect of adding two hydrophobic
      (stearic and palmitic) acids on the stability and magnetorheological effect of a
      suspension of CIMs in silicone oil was studied. According to the results, for
      preparing a stable and efficient magnetorheological (MR) fluid, additives should
      be utilized. Therefore, 3 wt% of stearic acid was added to the MR fluid which led
      to an enhancement of the fluid stability over 92% at 25  degrees C. By
      investigating shear stress variation due to the changes in the shear rate for
      acid-based MR fluids, the maximum yield stress was obtained by fitting the
      Bingham plastic rheological model at high shear rates. Based on the existing
      correlations of yield stress and either temperature or magnetic field strength, a
      new model was fitted to the experimental data to monitor the simultaneous effect
      of magnetic field strength and temperature on the maximum yield stress. The
      results demonstrated that as the magnetic field intensified or the temperature
      decreased, the maximum yield stress increased dramatically. In addition, when the
      MR fluid reached its magnetic saturation, the viscosity of fluid depended only on
      the shear rate. 

PMID- 25940852
TI  - Can Gestural Language Enhance Communication Between Surgeons and Operating
      Department Practitioners?

PMID- 25940851
TI  - The Relationship Between Volume Overload in End-Stage Renal Disease and
      Obstructive Sleep Apnea.
AB  - Obstructive sleep apnea (OSA) is common, underdiagnosed, and undertreated among
      patients with end-stage renal disease (ESRD). As in all cases, pathogenesis of
      OSA is related to repeated upper airway (UA) occlusion or narrowing, but in ESRD,
      additional contributory factors likely include uremic destabilization of central
      respiratory control and anatomic changes in the UA related to fluid status.
      Pulmonary congestion is common in acute and chronic kidney failure and is a
      consequence of cardiomyopathy and fluid overload, two potentially reversible risk
      factors. Emerging evidence suggests that volume overload also reduces the UA
      caliber. The diminution in UA area as well as destabilization of ventilatory
      control in ESRD have been postulated as causes of increased OSA prevalence and
      severity in these patients, and creates a vicious cycle wherein OSA exacerbates
      fluid overload disorders such as in congestive heart failure (CHF) and ESRD,
      which then further worsen OSA. Dialysis modalities may differ in their effects on
      volume status, the accumulation of uremic toxins, and acid-base status, and as a
      consequence, on the emergence and severity of OSA. Given the contribution of
      excess fluid to both the severity of nocturnal hypoxia and UA narrowing,
      establishing and maintaining dry weight is of particular importance when managing
      OSA in ESRD. Clinical trials to determine the extent to which more aggressive
      fluid removal in ESRD patients may alleviate OSA are needed. 

PMID- 25940853
TI  - Development of a New Magnetometer for Sentinel Lymph Node Mapping Designed for
      Video-Assisted Thoracic Surgery in Non-Small Cell Lung Cancer.
AB  - BACKGROUND: We previously developed a method for sentinel lymph node (SLN)
      mapping in non-small cell lung cancer (NSCLC), based on the magnetic force
      produced by a magnetite tracer already approved for use as a contrast material
      for magnetic resonance imaging. However, it is difficult to use that technique
      with video-assisted thoracic surgery (VATS) because the sensing element of the
      magnetometer is large and thick. The purpose of the present study was to develop
      a smaller, thinner VATS-compatible magnetometer. METHODS: The tracer employed was
      Ferucarbotran, a colloidal solution of superparamagnetic iron oxide coated with
      carbodextran. Fifteen patients with clinical stage I NSCLC were enrolled, and
      each received 1.6 mL of Ferucarbotran, injected intraoperatively at 5 points
      around the tumor. The magnetic force within the sampling lymph nodes was measured
      using the new VATS-compatible magnetometer. RESULTS: SLNs were detected in 11
      (73.3%) of the 15 patients using the VATS-compatible magnetometer. The average
      number of SLNs identified per patient was 1.8 (range 0-4). No complications
      related to the SLN detection method were observed. CONCLUSIONS: The new VATS
      compatible magnetometer appears to have substantial advantages over techniques
      using a radioisotope and our earlier magnetometer, as it can be inserted through
      the small VATS port site.

PMID- 25940854
TI  - Impact of liposomal bupivacaine administration on postoperative pain in patients
      undergoing total knee replacement.
AB  - STUDY OBJECTIVE: To determine whether liposomal bupivacaine, a long-acting
      anesthetic indicated for single-dose wound infiltration to produce postoperative
      analgesia, has an impact on postoperative pain in patients undergoing total knee
      arthroplasties (TKAs). DESIGN: Single-center retrospective cohort study. SETTING:
      Large tertiary and quaternary care hospital. PATIENTS: A total of 120 adults who
      underwent TKA between March 1, 2013, and October 31, 2013; of those patients, 55
      patients received an intraoperative dose of liposomal bupivacaine 266 mg (active
      treatment group), and 65 did not receive the drug (control group). MEASUREMENTS
      AND MAIN RESULTS: The primary end point was the mean area under the curve (AUC)
      of numeric rating scale (NRS) pain scores from the end of surgery to 48 hours
      after surgery. Secondary end points included measures of postoperative pain up to
      24 hours after surgery, opioid consumption within 48 hours after surgery,
      duration of hospitalization, and ambulation distance from the end of surgery to
      discharge. No significant differences were noted in the primary or secondary end
      points between patients who received or did not receive an intraoperative dose of
      liposomal bupivacaine. The mean +/- SD AUC of NRS pain scores was 199.59 +/-
      67.11 and 192.94 +/- 70.41 for the liposomal bupivacaine and control groups,
      respectively (p=0.658). Use of adjunctive analgesics was higher among patients in
      the control group, particularly for those receiving celecoxib, pregabalin, and
      continuous regional ropivacaine infusions, which may have minimized any
      differences in pain control between the treatment groups. CONCLUSION: Liposomal
      bupivacaine did not improve pain control in patients undergoing TKA when compared
      with historical management strategies; however, differences may have been
      obscured by increased utilization of adjunctive analgesics among patients in the
      control group.

PMID- 25940855
TI  - Assessment of surveys for the management of hospital clinical pharmacy services.
AB  - OBJECTIVE: Survey data sets are important sources of data, and their successful
      exploitation is of key importance for informed policy decision-making. We present
      how a survey analysis approach initially developed for customer satisfaction
      research in marketing can be adapted for an introduction of clinical pharmacy
      services into a hospital. METHODS AND MATERIAL: We use a data mining analytical
      approach to extract relevant managerial consequences. We evaluate the importance
      of competences for users of a clinical pharmacy with the OrdEval algorithm and
      determine their nature according to the users' expectations. For this, we need
      substantially fewer questions than are required by the Kano approach. RESULTS:
      From 52 clinical pharmacy activities we were able to identify seven activities
      with a substantial negative impact (i.e., negative reinforcement) on the overall
      satisfaction of clinical pharmacy services, and two activities with a strong
      positive impact (upward reinforcement). Using analysis of individual feature
      values, we identified six performance, 10 excitement, and one basic clinical
      pharmacists' activity. CONCLUSIONS: We show how the OrdEval algorithm can exploit
      the information hidden in the ordering of class and attribute values, and their
      inherent correlation using a small sample of highly relevant respondents. The
      visualization of the outputs turns out highly useful in our clinical pharmacy
      research case study.

PMID- 25940856
TI  - Learning from healthy and stable eyes: A new approach for detection of
      glaucomatous progression.
AB  - Glaucoma is a chronic neurodegenerative disease characterized by loss of retinal
      ganglion cells, resulting in distinctive changes in the optic nerve head (ONH)
      and retinal nerve fiber layer. Important advances in technology for non-invasive
      imaging of the eye have been made providing quantitative tools to measure
      structural changes in ONH topography, a crucial step in diagnosing and monitoring
      glaucoma. Three dimensional (3D) spectral domain optical coherence tomography (SD
      OCT), an optical imaging technique, is now the standard of care for diagnosing
      and monitoring progression of numerous eye diseases. METHOD: This paper aims to
      detect changes in multi-temporal 3D SD-OCT ONH images using a hierarchical fully
      Bayesian framework and then to differentiate between changes reflecting random
      variations or true changes due to glaucoma progression. To this end, we propose
      the use of kernel-based support vector data description (SVDD) classifier. SVDD
      is a well-known one-class classifier that allows us to map the data into a high
      dimensional feature space where a hypersphere encloses most patterns belonging to
      the target class. RESULTS: The proposed glaucoma progression detection scheme
      using the whole 3D SD-OCT images detected glaucoma progression in a significant
      number of cases showing progression by conventional methods (78%), with high
      specificity in normal and non-progressing eyes (93% and 94% respectively).
      CONCLUSION: The use of the dependency measurement in the SVDD framework increased
      the robustness of the proposed change-detection scheme with comparison to the
      classical support vector machine and SVDD methods. The validation using clinical
      data of the proposed approach has shown that the use of only healthy and non
      progressing eyes to train the algorithm led to a high diagnostic accuracy for
      detecting glaucoma progression compared to other methods.

PMID- 25940857
TI  - Inhibition of cyclooxygenase-2 causes a decrease in coronary flow in diabetic
      mice. The possible role of PGE2 and dysfunctional vasodilation mediated by
      prostacyclin receptor.
AB  - Several lines of evidence suggest that cyclooxygenase-2 (COX-2) activity can have
      a beneficial role in the maintenance of vascular tone of the blood vessels in
      diabetes. Specifically, the increased production of prostacyclin (PGI2) and
      prostaglandin E2 (PGE2), mediated by COX-2, has been suggested to compensate for
      decreased synthesis of nitric oxide (NO). The study investigates whether
      inhibition of COX-2 may reduce the coronary flow in diabetic animals and may also
      lead to decreased synthesis of prostaglandins. Mice aged 18-20 weeks were used
      for the study: those with leptin receptor deficiency (db/db) served as a model of
      diabetes while heterozygous (db/+) mice served as controls. Coronary flow was
      measured by the Langendorff method, and prostaglandin synthesis by myocardia was
      assayed in heart perfusates. COX-2 inhibition was found to reduce basal coronary
      flow in db/db mice but had no effect in db/+ mice. Secretion of PGE2 was found to
      be higher in db/db mice, while prostacyclin synthesis did not differ. COX-2
      inhibition decreased production of both prostaglandins to similar levels in both
      groups. The use of ONO-1301, a specific agonist for the prostacyclin receptor
      revealed that vasodilating responses mediated by the receptor were impaired in
      db/db mice. The expression levels of the receptor in cardiac tissue did not
      differ between the groups. It is concluded that the increased COX-2 contribution
      to vasodilation in diabetic animals appears to be partially a result of increased
      COX-2-dependent synthesis of PGE2 and also may be caused by impaired vasodilation
      mediated by the prostacyclin receptor. 

PMID- 25940858
TI  - Fistula formation between perianeurysmal hematoma and sigmoid colon: rare cause
      of lower gastrointestinal bleeding.

PMID- 25940859
TI  - Bioinspired High-Performance Energetic Materials Using Heme-Containing Crystals.
AB  - Synthetic hemozoin crystals (beta-hematin) are assembled with aluminium
      nanoparticles (nAl) to create a nanomaterial composite that is highly energetic
      and reactive. The results here demonstrate that hemozoin rapidly oxidizes the nAl
      fuel to release large amounts of energy (+12.5 +/- 2.4 kJ g(-1) ). 

PMID- 25940861
TI  - C-peptide levels in pediatric type 2 diabetes in the Pediatric Diabetes
      Consortium T2D Clinic Registry.
AB  - OBJECTIVE: To describe C-peptide levels in a large cohort of children with type 2
      diabetes T2D and examine associations with demographic and clinical factors.
      METHODS: The Pediatric Diabetes Consortium (PDC) T2D Registry has collected
      clinical and biologic data from youth with T2D cared for at eight US Pediatric
      Diabetes Centers. In this study, we assessed C-peptide levels in 331 youth with
      T2D (mean age, 16.1 +/- 2.5 yr; median T2D duration, 2.4 yr). RESULTS: Median
      (interquartile range) for 90 fasted C-peptide measurements was 3.5 ng/mL (2.3-4.8
      ng/mL) [1.2 nmol/L (0.8-1.6 nmol/L)] and for 241 random non-fasted C-peptide
      measurements were 4.2 ng/mL (2.6-7.0 ng/mL) [1.4 nmol/L (0.9-2.3 nmol/L)]. C
      peptide levels were lower with insulin therapy (p < 0.001), lower body mass index
      (p < 0.001), hemoglobin A1c (HbA1c) >=9% (p < 0.001), and T2D duration >= 6 yr (p
      = 0.04). Among those with duration >=6 yr being treated with insulin and with a
      HbA1c level >=9.0% (75 mmol/L), 75% of the fasted and 80% of the non-fasted C
      peptide values were above 0.2 nmol/L. CONCLUSIONS: In youth with T2D, a decline
      in C-peptide is associated with deterioration of metabolic control and the need
      for insulin treatment. C-peptide levels decrease over time. However, even insulin
      treated patients with 6 or more years of T2D and elevated HbA1c levels retain
      substantial endogenous insulin secretion.

PMID- 25940862
TI  - The Tomato yellow leaf curl virus V2 protein forms aggregates depending on the
      cytoskeleton integrity and binds viral genomic DNA.
AB  - The spread of Tomato yellow leaf curl virus (TYLCV) was accompanied by the
      formation of coat protein (CP) aggregates of increasing size in the cytoplasm and
      nucleus of infected tomato (Solanum lycopersicum) cells. In order to better
      understand the TYLCV-host interaction, we investigated the properties and the
      subcellular accumulation pattern of the non-structural viral protein V2. CP and
      V2 are the only sense-oriented genes on the virus circular single-stranded DNA
      genome. Similar to CP, V2 localized to cytoplasmic aggregates of increasing size
      and as infection progressed was also found in nuclei, where it co-localized with
      CP. V2 was associated with viral genomic DNA molecules, suggesting that V2
      functions as a DNA shuttling protein. The formation and the 26S proteasome
      mediated degradation of V2 aggregates were dependent on the integrity of the
      actin and microtubule cytoskeleton. We propose that the cytoskeleton-dependent
      formation and growth of V2 aggregates play an important role during TYLCV
      infection, and that microtubules and actin filaments are important for the
      delivery of V2 to the 26S proteasome. 

PMID- 25940863
TI  - Cost-effectiveness of a Barcelona home care program for individuals with
      multimorbidity.
AB  - To improve the efficiency and effectiveness of care and optimize healthcare
      resources, a home healthcare program was created for individuals with multiple
      chronic conditions. Demographic and clinical characteristics of the 261
      individuals (mean age 84) included in the program from its inception in 2011
      through 2013 (mean stay in the program 203+/-192 days) were prospectively
      analyzed. The number of hospital admissions, length of stay, and costs for
      individuals admitted to the program were compared for two time periods: the 6
      months before admission to the program and their stay in the program. After
      admission to the program, the number of hospital admissions and the hospital
      length of stay per person per month decreased from 0.36+/-0.21 to 0.19+/-0.52
      (P<.001) and from 3.5 to 1 day (P<.001), respectively. Surveys of randomly
      selected patients and caregivers showed high satisfaction with the program. Costs
      per person per day decreased from ?54.65 (US$73.12) to ?17.91 (US$23.96), a
      reduction of 67.1%. Fewer admissions and shorter hospital stays enabled the
      hospital to eliminate one acute bed for every 50 individuals admitted to the
      program. In conclusion, home care for individuals with chronic illness with
      multimorbidity reduced the number of hospital admissions and length of stay,
      resulting in good patient satisfaction and lower costs.

PMID- 25940864
TI  - Competitive stereocomplexation, homocrystallization, and polymorphic crystalline
      transition in poly(L-lactic acid)/poly(D-lactic acid) racemic blends: molecular
      weight effects.
AB  - Competitive crystallization kinetics, polymorphic crystalline structure, and
      transition of poly(l-lactic acid)/poly(d-lactic acid) (PLLA/PDLA) racemic blends
      with a wide range of molecular weights (MWs) were symmetrically investigated.
      Stereocomplex (sc) crystallites are exclusively formed in the low-MW racemic
      blends. However, stereocomplexation is remarkably depressed, and
      homocrystallization becomes prevailing with increasing MWs of PLLA and PDLA.
      Suppressed stereocomplexation in high-MW (HMW) racemic blends is proposed to be
      due to the low chain diffusion ability and restricted intermolecular crystal
      nucleation/growth. Equilibrium melting point of sc crystallites first increases
      and then decreases as MW increases. Crystallinity and relative fraction of sc
      crystallites in racemic blends enhance with crystallization temperature (Tc), and
      the sc crystallites are merely formed at Tc > 170  degrees C because of their
      higher thermodynamic stability. In situ wide-angle X-ray diffraction (WAXD)
      analysis reveals that the stereocomplexation and homocrystallization are
      successive rather than completely simultaneous, and the stereocomplexation is
      preceding homocrystallization in isothermal crystallization of HMW racemic
      blends. Both initial crystalline structure of homocrystallites (hc) and MW
      influence the heating-induced hc-to-sc transition of HMW racemic blend
      drastically; the hc-to-sc transition becomes easier with decreasing Tc and MW.
      After crystallization at the same temperature, sc crystallites show smaller long
      period than their hc counterparts. 

PMID- 25940865
TI  - ATR-FTIR measurements of albumin and fibrinogen adsorption: Inert versus calcium
      phosphate ceramics.
AB  - Arthritis, bone fracture, bone tumors and other musculoskeletal diseases affect
      millions of people across the world. Nowadays, inert and bioactive ceramics are
      used as bone substitutes or for bone regeneration. Their bioactivity is very much
      dictated by the way proteins adsorb on their surface. In this work, we compared
      the adsorption of albumin and fibrinogen on inert and calcium phosphates ceramics
      (CaPs) using attenuated total reflection Fourier transform infrared spectroscopy
      (ATR-FTIR) to follow in situ protein adsorption on these materials. To this
      effect, we developed a sol-gel technique to control the surface chemistry of an
      ATR-FTIR detector. Hydroxyapatite adsorbed more albumin and beta-tricalcium
      phosphate adsorbed more fibrinogen. Biphasic calcium phosphate presented the
      lowest adsorption among CaP for both proteins, illustrating the effect of surface
      heterogeneities. Inert ceramics adsorbed a lower amount of both proteins compared
      with bioactive ceramics. A significant change was observed in the conformation of
      the adsorbed protein versus the surface chemistry. Hydroxyapatite produced a
      larger loss of alpha-helix structure on albumin and biphasic calcium phosphate
      reduced beta-sheet percentage on fibrinogen. Inert ceramics produced large alpha
      helix loss on albumin and presented weak interaction with fibrinogen. Zirconia
      did not adsorb albumin and titanium dioxide promoted huge denaturalization of
      fibrinogen.

PMID- 25940866
TI  - CD8+ T cell profiles in patients with rheumatoid arthritis-the effects of
      costimulation blockade: comment on the article by Carvalheiro et al.

PMID- 25940867
TI  - Collagenase Clostridium histolyticum for the Treatment of Peyronie's Disease: The
      Development of This Novel Pharmacologic Approach.
AB  - INTRODUCTION: The conception of collagenase Clostridium histolyticum (CCH) as
      treatment for Peyronie's disease (PD) was a vital first step in providing a
      nonsurgical, minimally invasive FDA-approved treatment for men with PD. AIM: To
      review the origins, clinical research history, and ultimately FDA approval of
      collagenase as PD treatment. METHODS: A PubMed search using (Peyronie's or
      Peyronie) AND collagenase, and limited to clinical research studies, returned
      nine papers that were examined in the current review. RESULTS: Collagenase as a
      PD treatment arose in response to a lack of effective nonsurgical treatments and
      the incomplete understanding of underlying PD etiology. Awareness of dense
      collagen in PD scarring and parallel initial exploration of collagenase to treat
      herniated lumbar discs coincided with and inspired laboratory-based investigation
      of collagenase effects on excised PD plaque tissue. The foundational conceptual
      work and the critical development of purified injectable collagenase allowed the
      pursuit of clinical studies. Progression of clinical studies into large-scale
      robust trials culminated in two important outcomes: development of the first
      validated, PD-specific measure of psychosexual function, the Peyronie's Disease
      Questionnaire, and the first FDA-approved treatment for PD. CONCLUSIONS:
      Collagenase therapy began as an attempt to modify the structure of PD-related
      tunica albuginea scarring, despite the lack of a fundamental understanding of the
      scar's origin. If we wish to advance PD treatment beyond this first effective
      step, the future needs to bring us full circle to the starting point: We need a
      greater understanding of the control of collagen deposition and wound healing in
      men with PD.

PMID- 25940869
TI  - High prevalence of anaemia among African migrants in Germany persists after
      exclusion of iron deficiency and erythrocyte polymorphisms.
AB  - OBJECTIVES: Haematological parameters differ between individuals of African and
      European ancestry. However, respective data of first-generation African migrants
      are virtually absent. We assessed these in Ghanaian migrants living in Berlin,
      compared them with reference data from Germany and Ghana, and estimated the role
      of iron deficiency (ID) and erythrocyte polymorphisms in anaemia. METHODS: A
      total of 576 Ghanaians (median age, 45 years) were analysed. Blood counts were
      performed, haemoglobinopathies and glucose-6-phosphate dehydrogenase (G6PD)
      deficiency were genotyped, and concentrations of ferritin and C-reactive protein
      were measured to define ID. RESULTS: Most individuals had resided in Germany for
      more than a decade (median, 18 years). By WHO definition, anaemia was present in
      30.9% of females and 9.4% of males. Median haemoglobin (Hb) levels were lower
      than among Germans (women, -0.8 g/dl, men, -0.7 g/dl). However, applying
      reference values from Ghana, only 1.9% of the migrants were considered anaemic.
      Alpha-thalassaemia, Hb variants and G6PD deficiency were observed in 33.9%, 28.3%
      and 23.6%, respectively. ID was highly prevalent in women (32.0%; men, 3.9%). The
      population fraction of anaemia cases attributable to ID was 29.0% (alpha
      thalassaemia, 13.6%; G6PD deficiency, 13.5%). Nevertheless, excluding ID, alpha
      thalassaemia, G6PD deficiency and sickle cell disease, anaemia prevalence
      remained high (women, 18.4%; men, 6.5%), and was also high when applying
      uncensored thresholds proposed for African Americans (females, 19.3%; males,
      7.8%). CONCLUSIONS: Iron deficiency and erythrocyte polymorphisms are common
      among first-generation Ghanaian migrants but explain only part of the increased
      prevalence of anaemia. Common Hb thresholds for the definition of anaemia may not
      be appropriate for this group.

PMID- 25940868
TI  - Filopodia formation driven by membrane glycoprotein M6a depends on the
      interaction of its transmembrane domains.
AB  - Membrane glycoprotein M6a, which belongs to the tetraspan proteolipid protein
      family, promotes structural plasticity in neurons and cell lines by unknown
      mechanisms. This glycoprotein is encoded by Gpm6a, a stress-regulated gene. The
      hippocampus of animals chronically stressed by either psychosocial or physical
      stressors shows decreased M6a expression. Stressed Gpm6a-null mice develop a
      claustrophobia-like phenotype. In humans, de novo duplication of GPM6A results in
      learning/behavioral abnormalities, and two single-nucleotide polymorphisms (SNPs)
      in the non-coding region are linked to mood disorders. Here, we studied M6a
      dimerization in neuronal membranes and its functional relevance. We showed that
      the self-interaction of M6a transmembrane domains (TMDs) might be driving M6a
      dimerization, which is required to induce filopodia formation. Glycine mutants
      located in TMD2 and TMD4 of M6a affected its dimerization, thus preventing M6a
      induced filopodia formation in neurons. In silico analysis of three non
      synonymous SNPs located in the coding region of TMDs suggested that these
      mutations induce protein instability. Indeed, these SNPs prevented M6a from being
      functional in neurons, owing to decreased stability, dimerization or improper
      folding. Interestingly, SNP3 (W141R), which caused endoplasmic reticulum
      retention, is equivalent to that mutated in PLP1, W161L, which causes
      demyelinating Pelizaeus-Merzbacher disease. In this work we analyzed the
      functional contribution of transmembrane domains (TMDs) of the neuronal membrane
      glycoprotein M6a. We determined that certain glycines present in TMD2 and TMD4
      are critical for filopodia induction in neurons. In addition, three nsSNPs
      located in the coding region of TMD2 and TMD3 of GPM6A impair M6a function by
      affecting its stability, folding and dimer formation. 

PMID- 25940870
TI  - First report in a dog model of atopic dermatitis: expression patterns of protease
      activated receptor-2 and thymic stromal lymphopoietin.
AB  - BACKGROUND: Protease-activated receptor (PAR)-2 plays a crucial role in
      inflammation and the skin barrier. Protease-activated receptor-2 is activated by
      proteolytic enzymes of allergens and stimulates thymic stromal lymphopoietin
      (TSLP), promoting T-helper 2 cytokines. In humans with atopic dermatitis (AD),
      increased expression of PAR-2 and TSLP has been reported. HYPOTHESIS/OBJECTIVES:
      To compare the pattern of staining of PAR-2 and TSLP between normal and atopic
      beagle dogs. The hypothesis tested was that increased expression is present in
      atopic dog skin compared with healthy control skin. ANIMALS: Eight atopic and
      five normal dogs were challenged for 3 days with house dust mites. METHODS: Skin
      biopsies were taken to measure the intensity, distribution, integrity and cell
      staining pattern on days 0, 3 and 10, both objectively and subjectively. Clinical
      signs were scored and compared between groups. RESULTS: Atopic dogs showed a
      significant increase in clinical scores on days 3 (peak of challenge) and 10
      (resolution) and a significant condensed staining pattern for TSLP in the stratum
      basale at all times in comparison to normal dogs. They showed a significant
      patchy pattern for PAR-2 on days 0 and 3 and for TSLP at all times compared with
      normal dogs. The intensity itself was not significantly increased in atopic dogs
      compared with normal animals for both PAR-2 and TSLP. CONCLUSIONS AND CLINICAL
      IMPORTANCE: These preliminary findings do not confirm a difference in the amount
      of expression but rather in its pattern. Studies using PAR-2 or TSLP inhibitors
      could shed light on their clinical relevance.

PMID- 25940871
TI  - EPR spectroscopy identifies Met and Lys residues that are essential for the
      interaction between the CusB N-terminal domain and metallochaperone CusF.
AB  - Copper plays a key role in all living organisms by serving as a cofactor for a
      large variety of proteins and enzymes involved in electron transfer, oxidase and
      oxygenase activities, and the detoxification of oxygen radicals. Due to its
      toxicity, a conserved homeostasis mechanism is required. In E. coli, the CusCFBA
      efflux system is a copper-regulating system and is responsible for transferring
      Cu(I) and Ag(I) out of the periplasm domain into the extracellular domain. Two of
      the components of this efflux system, the CusF metallochaperone and the N
      terminal domain of CusB, have been thought to play significant roles in the
      function of this efflux system. Resolving the metal ion transport mechanism
      through this efflux system is vital for understanding metal- and multidrug
      resistant microorganisms. This work explores one aspect of the E. coli resistance
      mechanism by observing the interaction between the N-terminal domain of CusB and
      the CusF protein, using electron paramagnetic resonance (EPR) spectroscopy,
      circular dichroism (CD), and chemical cross-linking. The data summarized here
      show that M36 and M38 of CusB are important residues for both the Cu(I)
      coordination to the CusB N-terminal domain and the interaction with CusF, and K32
      is essential for the interaction with CusF. In contrast, the K29 residue is less
      consequential for the interaction with CusF, whereas M21 is mostly important for
      the proper interaction with CusF.

PMID- 25940872
TI  - Potential role of maternal lineage in the thoroughbred breeding strategy.
AB  - Many studies have focused on identifying the genes or single nucleotide
      polymorphisms associated with the athletic ability of thoroughbreds, but few have
      considered differences in maternal and paternal heritability of athletic ability.
      Herein, we report on our association study of career race performances of 675
      Australian thoroughbreds with their pedigrees. Racing performance data (prize
      money per start) were collected from the Bloodhound database. The performance of
      all horses was categorised as either poor or elite athletic achievement. Then,
      675 foals were divided by their parents' performance (elite or poor) into four
      groups: (1) elite dams and elite sires; (2) elite dams and poor sires; (3) poor
      dams and elite sires; and (4) poor dams and poor sires. The performance of foals
      was then compared between the four groups. The results show that the heritability
      of race performance between dams and foals (r = 0.141, P < 0.001) is much higher
      than that between sires and foals (r = 0.035, P = 0.366), and that this
      difference is statistically significant (P < 0.05). We also examined the effect
      of the child-bearing age of dams and sires on the ratio of elite foals. We found
      a strong correlation between the number of elite foals and dams' child-bearing
      age (r = -0.105, P < 0.001), with the ratio of elite offspring reaching a high
      level between a child-bearing age of 8 and 11 years (chi2 = 14.31, d.f. = 1, P <
      0.001). These findings suggest that the maternal line may play an important role
      in the selective breeding of athletic performance in thoroughbreds.

PMID- 25940873
TI  - [Juvenile rheumatoid diseases: Endoprosthetic care of destroyed hip joints].
AB  - BACKGROUND: Patients with juvenile idiopathic arthritis (JIA) often suffer from
      involvement of the hip joints, with joint destruction and related functional
      limitations, making hip replacement necessary. OBJECTIVES: To discover what
      special features are to be expected in patients with JIA and hip arthroplasty and
      what impact they have on surgical indication, choice of implant, and technique.
      METHODS: Selective literature review and evaluation of our patient population.
      RESULTS: Compared with osteoarthritis patients, JIA patients are on average much
      younger at the time of hip replacement. Owing to the onset of the disease in
      childhood or adolescence and the frequent glucocorticoid therapy, growth
      disorders or abnormal anatomical findings are common in these patients. Bone
      density is often reduced at an early age. The perioperative management of
      medication has to be planned. Special implants for patients with rheumatic
      diseases do not exist, but the above peculiarities of this group of patients
      should be considered for surgical procedure and choice of implant and material.
      Overall, the results of hip arthroplasty in juvenile rheumatic diseases, in terms
      of pain relief and functional improvement, are good. The limited life of the
      arthroplasty is problematic. CONCLUSIONS: By relieving pain, improvement of the
      range of motion and activity level very high patient satisfaction is usually
      achieved by hip arthroplasty in JIA patients. In the case of involvement of the
      contralateral hip or the ipsilateral knee joint it may be useful to perform a
      simultaneous, single-stage joint replacement of both joints.

PMID- 25940874
TI  - Parents' psychological well-being and parental self-efficacy in relation to the
      family's triadic interaction.
AB  - The aim of the study was to assess whether a parent's psychological well-being
      and/or self-efficacy relate to interaction within the family. This study is part
      of a Finnish follow-up study called Steps to the Healthy Development and Well
      Being of Children (STEPS;). The study group included 120 families. Mother's and
      father's social anxiety and depression were assessed during pregnancy and at 18
      months of the child's age using self-report questionnaires; the mother's and
      father's self-efficacy were assessed at 18 months using a parental self-efficacy
      scale validated within the STEPS study. Mother-father-child triadic interaction
      was studied at 18 months within a Lausanne Triadic Play setting. Results showed
      that maternal symptoms of depression during pregnancy and maternal social anxiety
      at 18 months were related to triadic interaction within the family. There was no
      relation between father's psychological well-being and triadic interaction within
      the family. Father's self-efficacy in teaching tasks and the Mother's self
      efficacy in emotional support were associated with family interaction. The
      findings suggest that maternal psychological well-being and self-efficacy in
      emotional support may be important components of family triadic interaction
      whereas paternal self-efficacy in teaching tasks seems to support family
      coordination in triadic interaction. 

PMID- 25940875
TI  - Choice, Rights, and Virtue: Prenatal Testing and Styles of Moral Reasoning in
      Aotearoa/New Zealand.
AB  - Using a Foucauldian biopower analytic, this article combines insights from
      several ethnographic research projects around the moral reasoning styles
      underpinning debates over selective reproductive technologies in Aotearoa/New
      Zealand. We show that divergent or shared public, private, state, individual, and
      community moral reasoning styles become highly politicized truth discourses that
      have the potential to, and at times do, affect one another, modifying a dominant,
      state-supported, principal-based bioethics framework. The styles of moral
      reasoning that we identify pivot on an aspirational cultural ideal of the
      provision of choice to citizens, which is taken as an appropriate position from
      which to regulate selective reproductive technologies. 

PMID- 25940876
TI  - Online and Offline Recruitment of Young Women for a Longitudinal Health Survey:
      Findings From the Australian Longitudinal Study on Women's Health 1989-95 Cohort.
AB  - BACKGROUND: In 2012, we set out to recruit a cohort of at least 10,000 women aged
      18-23 from across Australia. With recent research demonstrating the inadequacy of
      traditional approaches to recruiting women in this age group, we elected to
      conduct open recruiting. OBJECTIVE: Our aim was to report on the overall success
      of open recruiting and to evaluate the relative success of a variety of
      recruitment methods in terms of numbers and demographics. METHODS: We used
      referrals, Facebook, formal advertising, and incentives in order to recruit the
      cohort. RESULTS: In all, 17,069 women were recruited for the longitudinal online
      survey, from 54,685 initiated surveys. Of these women, most (69.94%, n=11,799)
      who joined the longitudinal cohort were recruited via Facebook, 12.72% (n=2145)
      via the fashion promotion, 7.02% (n=1184) by referral, 4.9% (n=831) via other Web
      activities, and 5.4% (n=910) via traditional media. CONCLUSIONS: Facebook was by
      far the most successful strategy, enrolling a cohort of women with a similar
      profile to the population of Australian women in terms of age, area of residence,
      and relationship status. Women recruited via fashion promotion were the least
      representative. All strategies underrepresented less educated women-a finding
      that is consistent with more traditional means of recruiting. In conclusion,
      flexibility in recruitment design, embracing new and traditional media, adopting
      a dynamic responsive approach, and monitoring the results of recruiting in terms
      of sample composition and number recruited led to the successful establishment of
      a new cohort.

PMID- 25940877
TI  - Installing and thereafter removing an aberrant prosthesis elicited opposite
      remodelling responses in growing mouse temporomandibular joints.
AB  - Temporomandibular joint (TMJ) displays a high remodelling capability. The current
      purpose was to investigate the differences between mandibular condylar
      remodelling responses of growing mice to installation and removal of unilateral
      anterior crossbite (UAC) prosthesis. Twenty-four mice were divided into one mock
      control group and two UAC groups. Unilateral anterior crossbite was created by
      installing a pair of prosthesis to left-side maxillary and mandibular incisors.
      Unilateral anterior crossbite was removed in removal group at 3 weeks but
      remained in UAC group. Temporomandibular joints were sampled at 7 weeks. Changes
      in condylar cartilage and subchondral bone were assessed by histology and in vivo
      micro-CT. Real-time PCR and immunohistochemistry were performed to evaluate
      expression changes in ADAMTS-5, MMP-3, MMP-9, MMP-13, IL-1, TNF-alpha, OPG and
      RANKL. Statistical analysis was performed at alpha = 0.05. Temporomandibular
      joint cartilage degradation was induced by UAC as previously reported but was
      reversed by removal of UAC. The dropped cartilage thickness, chondrocyte number
      and collagen II-positive area, the increased expression levels of Adamts-5, Mmp3,
      9, 13, Tnf-alpha and Il-1beta in cartilage, the decreased ratio of OPG/RANKL in
      both condylar cartilage and subchondral bone, the loss of TMJ subchondral bone
      and the increase in the TRAP-positive cells in subchondral bone were all reversed
      in the removal group (P < 0.05). The growing mouse TMJ condyle displays a high
      remodelling capability which can be degenerative and rehabilitative,
      respectively, in response to placement and thereafter removal of the aberrant
      prosthesis. Eliminating aberrant prosthesis is helpful to promote the degraded
      condyle to recover.

PMID- 25940878
TI  - Survival and neurological outcome following in-hospital paediatric
      cardiopulmonary resuscitation in North India.
AB  - BACKGROUND: Data on outcome of children undergoing in-hospital cardiopulmonary
      resuscitation (CPR) in low- and middle-income countries are scarce. AIMS: To
      describe the clinical profile and outcome of children undergoing in-hospital CPR.
      METHODS: This prospective observational study was undertaken in the Advanced
      Pediatric Center, PGIMER, Chandigarh. All patients aged 1 month to 12 years who
      underwent in-hospital CPR between July 2010 and March 2011 were included. Data
      were recorded using the 'Utstein style'. Outcome variables included 'sustained
      return of spontaneous circulation' (ROSC), survival at discharge and neurological
      outcome at 1 year. RESULTS: The incidence of in-hospital CPR in all hospital
      admissions (n = 4654) was 6.7% (n = 314). 64.6% (n = 203) achieved ROSC, 14% (n =
      44) survived to hospital discharge and 11.1% (n = 35) survived at 1 year. Three
      quarters of survivors had a good neurological outcome at 1-year follow-up. Sixty
      per cent of patients were malnourished. The Median Pediatric Risk of Mortality
      III (PRISM-III) score was 16 (IQR 9-25). Sepsis (71%), respiratory (39.5%) and
      neurological (31.5%) illness were the most common diagnoses. The most common
      initial arrhythmia was bradycardia (52.2%). On multivariate logistic regression,
      duration of CPR, diagnosis of sepsis and requirement for vasoactive support prior
      to arrest were independent predictors of decreased hospital survival.
      CONCLUSIONS: The requirement for in-hospital CPR is common in PGIMER. ROSC was
      achieved in two-thirds of children, but mortality was higher than in high-income
      countries because of delayed presentation, malnutrition and severity of illness.
      CPR >15 min was associated with death. Survivors had good long-term neurological
      outcome, demonstrating the value of timely CPR.

PMID- 25940880
TI  - Morphology controlled synthesis of monodispersed manganese sulfide nanocrystals
      and their primary application in supercapacitors with high performances.
AB  - Monodispersed hollow spindle-like nanosphere (HS-NS) and tetrapod nanorod (TP-NR)
      MnS nanocrystals are obtained via a facile template-free hydrothermal process.
      The MnS nanocrystals are used as supercapacitor materials and they exhibit high
      performances. The TP-NR nanocrystals show a higher specific capacitance of 704.5
      F g(-1) compared to the HS-NS nanocrystals, and both show higher values compared
      to manganese oxide. 

PMID- 25940879
TI  - Nestin as a marker of cancer stem cells.
AB  - The crucial role of cancer stem cells (CSCs) in the pathology of malignant
      diseases has been extensively studied during the last decade. Nestin, a class VI
      intermediate filament protein, was originally detected in neural stem cells
      during development. Its expression has also been reported in different tissues
      under various pathological conditions. Specifically, nestin has been shown to be
      expressed in transformed cells of various human malignancies, and a correlation
      between its expression and the clinical course of some diseases has been proved.
      Furthermore, the coexpression of nestin with other stem cell markers was
      described as a CSC phenotype that was subsequently verified using tumorigenicity
      assays. The primary aim of this review is to summarize the recent findings
      regarding nestin expression in CSCs, its possible role in CSC phenotypes,
      particularly with respect to capacity for self-renewal, and its utility as a
      putative marker of CSCs. 

PMID- 25940887
TI  - Adverse local tissue reaction (ALTR) associated with corrosion products in metal
      on-metal and dual modular neck total hip replacements is associated with
      upregulation of interferon gamma-mediated chemokine signaling.
AB  - Adverse local tissue reactions (ALTR) associated with tribocorrosion following
      total hip arthroplasty (THA) have become a significant clinical concern in recent
      years. In particular, implants featuring metal-on-metal bearing surfaces and
      modular femoral stems have been reported to result in elevated rates of ALTR.
      These tribocorrosion-related tissue reactions are characterized by marked
      necrosis and lymphocytic infiltration, which contrasts sharply with the
      macrophagic and foreign body giant cell inflammation associated with polyethylene
      wear particle induced peri-implant osteolysis. In this study, we characterize
      tribocorrosion-associated ALTR at a molecular level. Gene expression profiling of
      peri-implant tissue around failing implants identifies upregulation of numerous
      inflammatory mediators in ALTR, including several interferon gamma inducible
      factors, most notably the chemokines MIG/CXCL9 and IP-10/CXCL10. This expression
      profile is distinct from that associated with polyethylene wear induced
      osteolysis, which is characterized by induction of markers of alternative
      macrophage activation, such as chitotriosidase (CHIT-1). Importantly, MIG/CXCL9
      and IP-10/CXCL10 are also elevated at the protein level in the synovial fluid
      and, albeit more moderately, the serum, of ALTR patients, raising the possibility
      that these factors may serve as circulating biomarkers for the early detection of
      ALTR in at-risk patients.

PMID- 25940888
TI  - Hydrogen bonding between aromatic H and F groups leading to a stripe structure
      with R- and S-columns: the crystal structure of (2,7-dimethoxynaphthalen-1-yl)(3
      fluorophenyl)methanone and comparison with its 1-aroylnaphthalene analogues.
AB  - In the molecule of (2,7-dimethoxynaphthalen-1-yl)(3-fluorophenyl)methanone,
      C19H15FO3, (I), the dihedral angle between the plane of the naphthalene ring
      system and that of the benzene ring is 85.90 (5) degrees . The molecules exhibit
      axial chirality, with either an R- or an S-stereogenic axis. In the crystal
      structure, each enantiomer is stacked into a columnar structure and the columns
      are arranged alternately to form a stripe structure. A pair of (methoxy)C-H...F
      hydrogen bonds and pi-pi interactions between the benzene rings of the aroyl
      groups link an R- and an S-isomer to form a dimeric pair. These dimeric pairs are
      piled up in a columnar fashion through (benzene)C-H...O=C and (benzene)C-H...OCH3
      hydrogen bonds. The analogous 1-benzoylated compound, namely (2,7
      dimethoxynaphthalen-1-yl)(phenyl)methanone [Kato et al. (2010). Acta Cryst. E66,
      o2659], (II), affords three independent molecules having slightly different
      dihedral angles between the benzene and naphthalene rings. The three independent
      molecules form separate columns and the three types of column are connected to
      each other via two C-H...OCH3 hydrogen bonds and one C-H...O=C hydrogen bond. Two
      of the three columns are formed by the same enantiomeric isomer, whereas the
      remaining column consists of the counterpart isomer. In the case of the
      fluorinated 1-benzoylated naphthalene analogue, namely (2,7-dimethoxynaphthalen-1
      yl)(4-fluorophenyl)methanone [Watanabe et al. (2011). Acta Cryst. E67, o1466],
      (III), the molecular packing is similar to that of (I), i.e. it consists of
      stripes of R- and S-enantiomeric columns. A pair of C-H...F hydrogen bonds
      between R- and S-isomers, and C-H...O=C hydrogen bonds between R(or S)-isomers,
      are also observed. Consequently, the stripe structure is apparently induced by
      the formation of R...S dimeric pairs stacked in a columnar fashion. The pair of C
      H...F hydrogen bonds effectively stabilizes the dimeric pair of R- and S
      enantiomers. In addition, the co-existence of C-H...F and C-H...O=C hydrogen
      bonds makes possible the formation of a structure with just one independent
      molecule. 

PMID- 25940885
TI  - Asia, Australia and New Zealand Dyspnoea in Emergency Departments (AANZDEM)
      study: Rationale, design and analysis.
AB  - OBJECTIVES: Shortness of breath is a common reason for ED attendance. This
      international study aims to describe the epidemiology of dyspnoea presenting to
      EDs in the South East Asia-Pacific region, to compare disease patterns across
      regions, to understand how conditions are investigated and treated, and to assess
      quality of care. METHODS/DESIGN: This is a prospective, interrupted time series
      cohort study conducted in EDs in Australia, New Zealand, Singapore, Hong Kong and
      Malaysia of consecutive adult patients presenting to the ED with dyspnoea as a
      main symptom. Data were collected over three 72 h periods in May, August and
      October 2014 (autumn, winter and spring), and included demographics,
      comorbidities, mode of arrival, usual medications, pre-hospital treatment,
      initial assessment, ED investigations, treatment in the ED, ED diagnosis,
      disposition from ED, in-hospital outcome and final hospital diagnosis. The
      primary outcomes of interest are the epidemiology and outcome of patients
      presenting to ED with dyspnoea. Secondary outcomes of interest are seasonal and
      geographic comparisons of diagnoses and outcomes, disease-specific descriptions
      of epidemiology, investigation, treatment and disposition, and compliance with
      treatment guidelines. DISCUSSION: This novel study will explore dyspnoea from the
      viewpoint of the patient's symptom (shortness of breath) rather than that of a
      single disease. The results will provide robust data about the epidemiology,
      investigation, treatment and disposition of this diverse patient group. The
      obtained data also have the potential to inform service planning and to quantify
      the proportion of patients with mixed cardiac and respiratory disease.

PMID- 25940889
TI  - Synthesis, crystal structure and spectroscopic properties of trans
      dibromidobis(2,2-dimethylpropane-1,3-diamine-kappa(2)N,N')chromium(III)
      perchlorate.
AB  - The title complex salt, trans-anti-[CrBr2(Me2tn)2]ClO4 (where Me2tn = 2,2
      dimethylpropane-1,3-diamine, C5H14N2), was prepared and its structure determined
      by single-crystal X-ray diffraction at 100 K. The asymmetric unit contains three
      conformationally similar complex cations and three perchlorate anions. In each
      complex cation, the Cr(III) centre is coordinated by four N atoms of two
      chelating Me2tn ligands in the equatorial plane and by two Br atoms in a trans
      axial arrangement, to give a distorted octahedral geometry. Interionic contacts
      are dominated by extensive hydrogen bonding, involving the NH groups of the Me2tn
      ligand as donors and the anion O atoms or coordinated Br atoms as acceptors,
      resulting in two-dimensional layers in the bc plane. Ligand field analysis based
      on the angular overlap model, and IR and electronic spectroscopic properties, are
      also discussed. 

PMID- 25940890
TI  - 4,4'-Bipyridine-1,1'-diium acetylenedicarboxylate: a new member of the
      (H2bipy)[Cu(ox)2] (bipy is 4,4'-bipyridine and ox is oxalate) family.
AB  - 4,4'-Bipyridine-1,1'-diium (H2bipy) acetylenedicarboxylate, C10H12N2(2+).C4O4(2
      ), (1), is a new member of a family of related structures with similar unit-cell
      parameters. The structures in this family reported previously [Chen et al.
      (2012). CrystEngComm, 14, 6400-6403] are (H2bipy)[Cu(ox)2] (ox is oxalate), (2),
      (H2bipy)[NaH(ox)2], (3), and (H2bipy)[H2(ox)2], (4). Compound (1) has a one
      dimensional structure, in which H2bipy(2+) cations and acetylenedicarboxylate
      (ADC(2-)) anions are linked through a typical supramolecular synthon, i.e.
      R2(2)(7), and form linear '-cation-anion-' ribbons. Through an array of
      nonclassical C-H...O hydrogen bonds, adjacent ribbons interact to give two
      dimensional sheets. These sheets stack to form a layered structure via pi-pi
      interactions between the H2bipy(2+) cations of neighbouring layers. The
      supramolecular isostructurality of compounds (1)-(4) is ascribed to the
      synergistic effect of multiple interactions in these structures. The balanced
      strong and weak intermolecular interactions stabilizing this structure type
      include strong charge-assisted N-H...O hydrogen bonds, C-H...O contacts and pi-pi
      interactions. 

PMID- 25940892
TI  - A novel two-dimensional cadmium(II) complex: poly[diaquatris(MU4-cyclohexane-1,4
      dicarboxylato)bis[2-(pyridin-4-yl)-1H-benzimidazole]tricadmium(II).
AB  - The title compound, [Cd3(C8H10O4)3(C12H9N3)2(H2O)2]n or [Cd3(chdc)3(4
      PyBIm)2(H2O)2]n, was synthesized hydrothermally from the reaction of
      Cd(CH3COO)2.2H2O with 2-(pyridin-4-yl)-1H-benzimidazole (4-PyBIm) and cyclohexane
      1,4-dicarboxylic acid (1,4-chdcH2). The asymmetric unit consists of one and a
      half Cd(II) cations, one 4-PyBIm ligand, one and a half 1,4-chdc(2-) ligands and
      one coordinated water molecule. The central Cd(II) cation, located on an
      inversion centre, is coordinated by six carboxylate O atoms from six 1,4-chdc(2-)
      ligands to complete an elongated octahedral coordination geometry. The two
      terminal rotationally symmetric Cd(II) cations each exhibits a distorted
      pentagonal-bipyramidal geometry, coordinated by one N atom from 4-PyBIm, five O
      atoms from three 1,4-chdc(2-) ligands and one O atom from an aqua ligand. The 1,4
      chdc(2-) ligands possess two conformations, i.e. e,e-trans-chdc(2-) and e,a-cis
      chdc(2-). The cis-1,4-chdc(2-) ligands bridge the Cd(II) cations to form a
      trinuclear {Cd3}-based chain along the b axis, while the trans-1,4-chdc(2-)
      ligands further link adjacent one-dimensional chains to construct an interesting
      two-dimensional network. 

PMID- 25940893
TI  - A dihydrogen phosphate anionic network as a host lattice for cations in 1
      methylpiperazine-1,4-diium bis(dihydrogen phosphate) and 2-(pyridin-2
      yl)pyridinium dihydrogen phosphate-orthophosphoric acid (1/1).
AB  - In the salt 1-methylpiperazine-1,4-diium bis(dihydrogen phosphate),
      C5H13N2(2+).2H2PO4(-), (I), and the solvated salt 2-(pyridin-2-yl)pyridinium
      dihydrogen phosphate-orthophosphoric acid (1/1), C10H9N2(+).H2PO4(-).H3PO4, (II),
      the formation of O-H...O and N-H...O hydrogen bonds between the dihydrogen
      phosphate (H2PO4(-)) anions and the cations constructs a three- and two
      dimensional anionic-cationic network, respectively. In (I), the self-assembly of
      H2PO4(-) anions forms a two-dimensional pseudo-honeycomb-like supramolecular
      architecture along the (010) plane. 1-Methylpiperazine-1,4-diium cations are
      trapped between the (010) anionic layers through three N-H...O hydrogen bonds. In
      solvated salt (II), the self-assembly of H2PO4(-) anions forms a two-dimensional
      supramolecular architecture with open channels projecting along the [001]
      direction. The 2-(pyridin-2-yl)pyridinium cations are trapped between the open
      channels by N-H...O and C-H...O hydrogen bonds. From a study of previously
      reported structures, dihydrogen phosphate anions show a supramolecular
      flexibility depending on the nature of the cations. The dihydrogen phosphate
      anion may be suitable for the design of the host lattice for host-guest
      supramolecular systems. 

PMID- 25940891
TI  - Two different products from the reaction of 1-aryl-5-chloro-3-methyl-1H-pyrazole
      4-carbaldehyde with cyclohexylamine when the aryl substituent is phenyl or
      pyridin-2-yl: hydrogen-bonded sheets versus dimers.
AB  - Cyclohexylamine reacts with 5-chloro-3-methyl-1-(pyridin-2-yl)-1H-pyrazole-4
      carbaldehyde to give 5-cyclohexylamino-3-methyl-1-(pyridin-2-yl)-1H-pyrazole-4
      carbaldehyde, C16H20N4O, (I), formed by nucleophilic substitution, but with 5
      chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde the product is (Z)-4
      [(cyclohexylamino)methylidene]-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one, C17H21N3O,
      (II), formed by condensation followed by hydrolysis. Compound (II) crystallizes
      with Z' = 2, and in one of the two independent molecular types the
      cyclohexylamine unit is disordered over two sets of atomic sites having
      occupancies of 0.65 (3) and 0.35 (3). The vinylogous amide portion in each
      compound shows evidence of electronic polarization, such that in each the O atom
      carries a partial negative charge and the N atom of the cyclohexylamine portion
      carries a partial positive charge. The molecules of (I) contain an intramolecular
      N-H...N hydrogen bond, and they are linked by C-H...O hydrogen bonds to form
      sheets. Each of the two independent molecules of (II) contains an intramolecular
      N-H...O hydrogen bond and each molecular type forms a centrosymmetric dimer
      containing one R2(2)(4) ring and two inversion-related S(6) rings. 

PMID- 25940894
TI  - Carbonyl-carbonyl interactions and amide pi-stacking as the directing motifs of
      the supramolecular assembly of ethyl N-(2-acetylphenyl)oxalamate in a
      synperiplanar conformation.
AB  - The title compound, C12H13NO4, is one of the few examples that exhibits a syn
      conformation between the amide and ester carbonyl groups of the oxalyl group.
      This conformation allows the engagement of the amide H atom in an intramolecular
      three-centred hydrogen-bonding S(6)S(5) motif. The compound is self-assembled by
      C=O...C=O and amide-pi interactions into stacked columns along the b-axis
      direction. The concurrence of both interactions seems to be responsible for
      stabilizing the observed syn conformation between the carbonyl groups. The second
      dimension, along the a-axis direction, is developed by soft C-H...O hydrogen
      bonding. Density functional theory (DFT) calculations at the B3LYP/6-31G(d,p)
      level of theory were performed to support the experimental findings. 

PMID- 25940895
TI  - (2-Aminopyrimidine-kappaN(1))aqua(pyridine-2,6-dicarboxylato
      kappa(3)O(2),N,O(6))copper(II): X-ray and DFT calculated structure.
AB  - In the title compound, [Cu(C7H3N2O4)(C4H5N2)(H2O)], (I), pyridine-2,6
      dicarboxylate (pydc(2-)), 2-aminopyrimidine and aqua ligands coordinate the
      Cu(II) centre through two N atoms, two carboxylate O atoms and one water O atom,
      respectively, to give a nominally distorted square-pyramidal coordination
      geometry, a common arrangement for copper complexes containing the pydc(2-)
      ligand. Because of the presence of Cu...Xbridged contacts (X = N or O) between
      adjacent molecules in the crystal structures of (I) and three analogous
      previously reported compounds, and the corresponding uncertainty about the
      effective coordination number of the Cu(II) centre, density functional theory
      (DFT) calculations were used to elucidate the degree of covalency in these
      contacts. The calculated Wiberg and Mayer bond-order indices reveal that the
      Cu...O contact can be considered as a coordination bond, whereas the amine group
      forming a Cu...N contact is not an effective participant in the coordination
      environment. 

PMID- 25940896
TI  - Expanding the structural landscape of niclosamide: a high Z' polymorph, two new
      solvates and monohydrate H(A).
AB  - Three new crystalline phases are reported for the drug niclosamide [5-chloro-N-(2
      chloro-4-nitrophenyl)-2-hydroxybenzamide], C13H8Cl2N2O4. A new high-Z' polymorph
      (denoted Form II) is described, with four molecules in the asymmetric unit in the
      space group P2/n. The structure exhibits pseudosymmetry, including local
      translations and screw-type operations. The niclosamide molecules are linked by O
      H...O hydrogen bonds into chains, and the chains are packed so that the molecules
      form face-to-face (stacking) and end-to-end interactions within layers
      perpendicular to the chains. There are two different layer arrangements, giving a
      structure that is relatively complex. In the acetone and acetonitrile solvates,
      the incorporated solvent molecules accept hydrogen bonds from the OH groups of
      niclosamide, and the niclosamide molecules are stacked in a face-to-face manner.
      In the acetone solvate, C13H8Cl2N2O4.C3H6O, V-shaped arrangements are formed in
      which the nitrobenzene ends of the niclosamide molecules are brought into face-to
      face contact. In the acetonitrile solvate, C13H8Cl2N2O4.CH3CN, stacking occurs by
      translation along a short axis (ca 3.8 A) and the crystals are frequently
      observed to be twinned by twofold rotation around that axis. The acetonitrile
      molecules occupy channels in the structure. A complete structure is provided for
      niclosamide monohydrate, C13H8Cl2N2O4.H2O, polymorph HA, obtained by Rietveld
      refinement against laboratory powder X-ray diffraction data. It has been
      suggested that this compound is related to the methanol solvate of niclosamide
      [Harriss, Wilson & Radosevljevic Evans (2014). Acta Cryst. C70, 758-763], but it
      is found that the two are not fully isostructural: they contain isostructural two
      dimensional layers, but the layers are arranged differently in the two
      structures. This suggests that HA may have the potential for polytypism, and
      features in the Rietveld difference curve indicate that a polytype fully
      isostructural with the methanol solvate might be present. 

PMID- 25940897
TI  - The first structurally analysed nucleic acid building block containing the Reese
      protecting group: 2'-O-[1-(2-fluorophenyl)-4-methoxypiperidin-4-yl]-beta-D
      (1'R,2'R,3'R,4'R)-uridine.
AB  - The title compound, C21H26FN3O7, is assembled by N-H...O and O-H...O hydrogen
      bonds into well-separated two-dimensional layers of about 15 A thickness. The
      crescent conformation of the molecules is stabilized by weak intramolecular C
      H...O and C-H...F hydrogen bonds. The uridine moiety adopts an anti conformation.
      The ribofuranose ring exists in an envelope conformation. All the endocyclic
      uracil bonds are shorter than normal single C-N and C-C bonds, and five of them
      have comparable lengths, which implies a considerable degree of delocalization of
      the electron density within this ring. 

PMID- 25940898
TI  - A square-planar tellurium(II) complex with Te,Te'-chelating ligands.
AB  - While exploring the chemistry of tellurium-containing
      dichalcogenidoimidodiphosphinate ligands, the first all-tellurium member of a
      series of related square-planar E(II)(E')4 complexes (E and E' are group 16
      elements), namely bis(P,P,P',P'-tetraphenylditelluridoimidodiphosphinato
      kappa(2)Te,Te')tellurium(II) (systematic name: 2,2,4,4,8,8,10,10-octaphenyl
      1lambda(3),5,6lambda(4),7lambda(3),11-pentatellura-3,9-diaza
      2lambda(5),4lambda(5),8lambda(5),10lambda(5)-tetraphosphaspiro[5.5]undeca-1,3,7,9
      tetraene), C48H40N2P4Te5, was obtained unexpectedly. The formally Te(II) centre
      is situated on a crystallographic inversion centre and is Te,Te'-chelated to two
      anionic [(TePPh2)2N](-) ligands in an anti conformation. The central Te(II)(Te)4
      unit is approximately square planar [Te-Te-Te = 93.51 (3) and 86.49 (3) degrees
      ], with Te-Te bond lengths of 2.9806 (6) and 2.9978 (9) A. 

PMID- 25940899
TI  - The crystal and molecular structure of sodium 4-(2,4,6
      triisopropylbenzoyl)benzoate in terms of the photochemical behaviour of the
      anion.
AB  - Contrary to the known 4-(2,4,6-triisopropylbenzoyl)benzoate salts, di-MU-aqua
      bis[tetraaquasodium(I)] bis[4-(2,4,6-triisopropylbenzoyl)benzoate] dihydrate,
      [Na2(H2O)10](C23H27O3)2.2H2O, (1), does not undergo a photochemical Norrish-Yang
      reaction in the crystalline state. In order to explain this photochemical
      inactivity, the intermolecular interactions were analyzed by means of the
      Hirshfeld surface and intramolecular geometrical parameters describing the
      possibility of a Norrish-Yang reaction were calculated. The reasons for the
      behaviour of the title salt are similar crystalline environments for both the o
      isopropyl groups in the anion, resulting in similar geometrical parameters and
      orientations, and that these interaction distances differ significantly from
      those found in salts where the photochemical reaction occurs. 

PMID- 25940900
TI  - L-Argininium phosphite - a new candidate for NLO materials.
AB  - In order to investigate the possibility of salt formation in the L-Arg-H3PO3-H2O
      system, single crystals of L-argininium phosphite, C6H15N4O2(+).H2PO3(-), were
      prepared by evaporation of an aqueous solution containing equimolar quantities of
      L-arginine and phosphorous acid. The asymmetric unit contains one L-argininium(+)
      cation and one phosphite [HPO2(OH)](-) anion. The phosphite anions form chains
      parallel to [010] by O-H...O hydrogen bonding, with an O...O distance of 2.630
      (3) A. The protonated amine and guanidyl groups of the L-argininium(+) cations
      form N-H...O hydrogen bonds with the carboxylate groups and anions. The IR and
      Raman spectra are discussed in relation to the crystal structure. The salt
      displays nonlinear optical (NLO) properties. Another salt was obtained from a
      solution with a 1:2 molar ratio of components, but was characterized by
      vibrational spectra only. 

PMID- 25940901
TI  - Corrigenda for four articles.
AB  - The acknowledgement text is corrected in four articles: Li, Wang & Ye [Acta
      Cryst. (2014), C70, 992-997], Li & Wang [Acta Cryst. (2014), C70, 1054-1056], Li
      [Acta Cryst. (2015), C71, 65-68] and Li, Wang & Zhou [Acta Cryst. (2015), C71, 93
      96]. 

PMID- 25940902
TI  - Thiopurine methyltransferase and treatment outcome in the UK acute lymphoblastic
      leukaemia trial ALL2003.
AB  - The influence of thiopurine methyltransferase (TPMT) genotype on treatment
      outcome was investigated in the United Kingdom childhood acute lymphoblastic
      leukaemia trial ALL2003, a trial in which treatment intensity was adjusted based
      on minimal residual disease (MRD). TPMT genotype was measured in 2387 patients
      (76% of trial entrants): 2190 were homozygous wild-type, 189 were heterozygous
      for low activity TPMT alleles (166 TPMT*1/*3A, 19 TPMT*1/*3C, 3 TPMT*1/*2 and 1
      TPMT*1/*9) and 8 were TPMT deficient. In contrast to the preceding trial ALL97,
      there was no difference in event-free survival (EFS) between the TPMT genotypes.
      The 5-year EFS for heterozygous TPMT*1/*3A patients was the same in both trials
      (88%), but for the homozygous wild-type TPMT*1/*1 patients, EFS improved from 80%
      in ALL97% to 88% in ALL2003. Importantly, the unexplained worse outcome for
      heterozygous TPMT*1/*3C patients observed in ALL97 (5-year EFS 53%) was not seen
      in ALL2003 (5-year EFS 94%). In a multivariate Cox regression analysis the only
      significant factor affecting EFS was MRD status (hazard ratio for high-risk MRD
      patients 4.22, 95% confidence interval 2.97-5.99, P < 0.0001). In conclusion,
      refinements in risk stratification and treatment have reduced the influence of
      TPMT genotype on treatment outcome in a contemporary protocol. 

PMID- 25940903
TI  - The guanidinium unit in the catalysis of phosphoryl transfer reactions: from
      molecular spacers to nanostructured supports.
AB  - Examples of guanidinium-based artificial phosphodiesterases are illustrated in
      this review article. A wide set of collected catalytic systems are presented,
      from the early examples to the most recent developments of the use of this unit
      in the design of supramolecular catalysts. Special attention is dedicated to
      illustrate the operating catalytic mechanism and the role of guanidine/ium units
      in the catalysis. One or more of these units can act by themselves or in
      conjunction with other active units. The analogy with the mechanism of enzymatic
      systems is presented and discussed. In the last part of this overview, recent
      examples of guanidinophosphodiesterases based on nanostructured supports are
      reported, namely gold-monolayer-protected clusters and polymer brushes grafted to
      silica nanoparticles. The issue of the dependence of the catalytic performance on
      the preorganization of the spacer is tackled and discussed in terms of effective
      molarity, a parameter that can be taken as a quantitative measurement of this
      preorganization for both conventional molecular linker and nanosized supports. 

PMID- 25940904
TI  - Regulation of recombination at yeast nuclear pores controls repair and triplet
      repeat stability.
AB  - Secondary structure-forming DNA sequences such as CAG repeats interfere with
      replication and repair, provoking fork stalling, chromosome fragility, and
      recombination. In budding yeast, we found that expanded CAG repeats are more
      likely than unexpanded repeats to localize to the nuclear periphery. This
      positioning is transient, occurs in late S phase, requires replication, and is
      associated with decreased subnuclear mobility of the locus. In contrast to
      persistent double-stranded breaks, expanded CAG repeats at the nuclear envelope
      associate with pores but not with the inner nuclear membrane protein Mps3.
      Relocation requires Nup84 and the Slx5/8 SUMO-dependent ubiquitin ligase but not
      Rad51, Mec1, or Tel1. Importantly, the presence of the Nup84 pore subcomplex and
      Slx5/8 suppresses CAG repeat fragility and instability. Repeat instability in
      nup84, slx5, or slx8 mutant cells arises through aberrant homologous
      recombination and is distinct from instability arising from the loss of ligase 4
      dependent end-joining. Genetic and physical analysis of Rad52 sumoylation and
      binding at the CAG tract suggests that Slx5/8 targets sumoylated Rad52 for
      degradation at the pore to facilitate recovery from acute replication stress by
      promoting replication fork restart. We thereby confirmed that the relocation of
      damage to nuclear pores plays an important role in a naturally occurring repair
      process. 

PMID- 25940905
TI  - Using Sociograms to Enhance Power and Voice in Focus Groups.
AB  - OBJECTIVE: To discuss the use of sociograms in our focus groups with homeless
      sheltered mothers and to assess facilitator influence and the distribution of
      power influence. DESIGN AND SAMPLE: An exploratory, descriptive qualitative
      design that utilizes both focus groups and sociograms. Two focus groups were
      conducted in December 2009 (N = 7) and January 2010 (N = 4). Data analysis
      included a content analysis and a process analysis using sociograms to
      graphically represent group participant dynamics. RESULTS: Use of the sociogram
      provided a means to assess the influence of the facilitator as well as quantify
      the degree to which group participants' voices are included. CONCLUSION: Using
      sociograms provides a viable mechanism to complement content analysis and
      increase the methodological rigor of focus groups in health care research.

PMID- 25940907
TI  - Characterization of a new HLA allele: A*02:548.
AB  - HLA-A*02:548 differs from A*02:01:01:01 by one nucleotide at position 367T > C
      resulting in histidine at codon 99. 

PMID- 25940908
TI  - Extreme physiological gynaecomastia in the neonate: Observation not intervention.

PMID- 25940909
TI  - Glycogen storage diseases of all types.

PMID- 25940910
TI  - Hypoxanthine deregulates genes involved in early neuronal development.
      Implications in Lesch-Nyhan disease pathogenesis.
AB  - Neurological manifestations in Lesch-Nyhan disease (LND) are attributed to the
      effect of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency on the
      nervous system development. HPRT deficiency causes the excretion of increased
      amounts of hypoxanthine into the extracellular medium and we hypothesized that
      HPRT deficiency related to hypoxanthine excess may then lead, directly or
      indirectly, to transcriptional aberrations in a variety of genes essential for
      the function and development of striatal progenitor cells. We have examined the
      effect of hypoxanthine excess on the differentiation of neurons in the well
      established human NTERA-2 cl.D1 (NT2/D1) embryonic carcinoma neurogenesis model.
      NT2/D1 cells differentiate along neuroectodermal lineages after exposure to
      retinoic acid (RA). Hypoxanthine effects on RA-differentiation were examined by
      the changes on the expression of various transcription factor genes essential to
      neuronal differentiation and by the changes in tyrosine hydroxylase (TH),
      dopamine, adenosine and serotonin receptors (DRD, ADORA, HTR). We report that
      hypoxanthine excess deregulate WNT4, from Wnt/beta-catenin pathway, and engrailed
      homeobox 1 gene and increased TH and dopamine DRD1, adenosine ADORA2A and
      serotonin HTR7 receptors, whose over expression characterize early neuro
      developmental processes.

PMID- 25940906
TI  - Dose-response relationship between methadone dose and adherence to antiretroviral
      therapy among HIV-positive people who use illicit opioids.
AB  - BACKGROUND AND AIMS: For HIV-positive individuals who use illicit opioids,
      engagement in methadone maintenance therapy (MMT) can contribute to improved HIV
      treatment outcomes. However, to our knowledge, the role of methadone dosing in
      adherence to antiretroviral therapy (ART) has not yet been investigated. We
      sought to examine the relationship between methadone dose and ART adherence among
      a cohort of people who use illicit opioids. DESIGN AND SETTING: We used data from
      the AIDS Care Cohort to Evaluate Access to Survival Services (ACCESS) study, an
      ongoing prospective observational cohort of HIV-positive people who use illicit
      drugs in Vancouver, Canada, linked confidentially to comprehensive HIV treatment
      data in a setting of universal no-cost medical care, including medications. We
      evaluated the longitudinal relationship between methadone dose and the likelihood
      of >= 95% adherence to ART among ART-exposed participants during periods of
      engagement in MMT. PARTICIPANTS: Two hundred and ninety-seven ART-exposed
      individuals on MMT were recruited between December 2005 and May 2013 and followed
      for a median of 42.1 months. MEASUREMENTS: We measured methadone dose at >= 100
      versus < 100 mg/day and the likelihood of >= 95% adherence to ART. FINDINGS: In
      adjusted generalized estimating equation (GEE) analyses, MMT dose >= 100 mg/day
      was associated independently with optimal adherence to ART [adjusted odds ratio
      (AOR) = 1.38; 95% confidence interval (CI) = 1.08-1.77). In a subanalysis, we
      observed a dose-response relationship between increasing MMT dose and ART
      adherence (AOR = 1.06 per 20 mg/day increase, 95% CI = 1.00-1.12). CONCLUSION:
      Among HIV-positive individuals in methadone maintenance therapy, those receiving
      higher doses of methadone (>= 100 mg/day) are more likely to achieve >= 95%
      adherence to antiretroviral therapy than those receiving lower doses.

PMID- 25940911
TI  - Ultramild protein-mediated click chemistry creates efficient oligonucleotide
      probes for targeting and detecting nucleic acids.
AB  - Functionalized synthetic oligonucleotides are finding growing applications in
      research, clinical studies, and therapy. However, it is not easy to prepare them
      in a biocompatible and highly efficient manner. We report a new strategy to
      synthesize oligonucleotides with promising nucleic acid targeting and detection
      properties. We focus in particular on the pH sensitivity of these new probes and
      their high target specificity. For the first time, human copper(I)-binding
      chaperon Cox17 was applied to effectively catalyze click labeling of
      oligonucleotides. This was performed under ultramild conditions with fluorophore,
      peptide, and carbohydrate azide derivatives. In thermal denaturation studies, the
      modified probes showed specific binding to complementary DNA and RNA targets.
      Finally, we demonstrated the pH sensitivity of the new rhodamine-based
      fluorescent probes in vitro and rationalize our results by electronic structure
      calculations.

PMID- 25940913
TI  - Dinutuximab: first global approval.
AB  - United Therapeutics Corporation and the National Cancer Institute are developing
      dinutuximab (UnituxinTM; ch14.18), a monoclonal antibody targeting GD2, for the
      treatment of neuroblastoma. GD2 is a glycolipid found on the surface of tumour
      cells, which is overexpressed in neuroblastoma. Dinutuximab, an IgG1 human/mouse
      chimeric switch variant of murine monoclonal antibody 14G2a, binds to GD2 and
      induces antibody-dependent cell-mediated cytotoxicity and complement-dependent
      cytotoxicity. The US FDA has recently approved the use of dinutuximab combination
      therapy for the treatment of high-risk neuroblastoma in paediatric patients. The
      marketing authorization application for dinutuximab is under regulatory review in
      the EU, and phase I-III development is underway in several other countries. This
      article summarizes the milestones in the development of dinutuximab leading to
      this first approval for use (in combination with granulocyte macrophage colony
      stimulating factor, interleukin-2 and 13-cis retinoic acid) in the treatment of
      paediatric patients with high-risk neuroblastoma who achieve at least partial
      response to prior first-line multiagent, multimodality therapy.

PMID- 25940912
TI  - Targeting interferons in systemic lupus erythematosus: current and future
      prospects.
AB  - Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown
      aetiology that can be debilitating and life threatening. As new insights are
      gained into the underlying pathology of SLE, there have been an unprecedented
      number of new agents under development to treat the disease via a diverse range
      of targets. One such class of emerging agents target interferon (IFN) signalling.
      In this article, we review the preclinical evidence that the inhibition of the
      secretion and downstream effectors of both IFN-alpha and IFN-gamma may be
      effective for the treatment of SLE. The primary agents that are currently in
      clinical development to treat SLE via the targeting of interferon pathways are
      monoclonal neutralising antibodies (Mab) that bind to and neutralise IFN-gamma
      (AMG 811), IFN-alpha (sifalimumab, rontalizumab and AGS-009) or its receptor
      (anifrolumab), and IFN-alpha kinoid, which is a drug composed of inactivated IFN
      alpha molecules coupled to the keyhole limpet haemocyanin protein. Phase I and II
      trials have demonstrated acceptable short-term safety with no increase in severe
      viral infections or reactivation, favourable pharmacokinetic profiles and an
      inhibition of IFN-associated gene overexpression; however, the impact of these
      drugs on disease activity must still be assessed in phase III clinical trials.
      This review concludes with a summary of the challenges that are inherent to this
      approach to managing SLE.

PMID- 25940914
TI  - Intracellular zinc is a critical intermediate in the excitotoxic cascade.
AB  - Excessive and sustained exposure to glutamate leads to injurious elevations of
      cytosolic calcium ([Ca(2+)]i), generation of reactive oxygen and nitrogen species
      (ROS, RNS), mitochondrial failure, mobilization of intracellular zinc
      ([Zn(2+)]i), and, ultimately, neuronal death. The relative contribution and
      temporal dynamics of the activation of these processes to promote the full
      development of excitotoxicity are still not completely understood. In this study,
      we exploited the unique features of nNOS positive neurons [nNOS (+)], a striatal
      subpopulation that is constitutively spared from NMDAR-dependent insults, and
      dissected NMDAR-driven [Ca(2+)]i, [Zn(2+)]i, ROS, and mitochondrial changes
      occurring in these neurons and the overall population of nNOS (-) striatal
      neurons. Comparing the two populations and employing pharmacological,
      biochemical, and single-cell imaging techniques, we show that [Zn(2+)]i
      mobilization acts as a critical intermediate in the cascade that links NMDAR
      mediated ROS overproduction, mitochondrial failure, and [Ca(2+)]i deregulation to
      the production of neuronal damage. Results of this study may also provide the
      rationale for aiming at therapeutic agents that favor Zn(2+) homeostasis for the
      treatment of acute or chronic neurological conditions associated with
      excitotoxicity. 

PMID- 25940915
TI  - Proposal for novel histological findings of colorectal liver metastases with
      preoperative chemotherapy.
AB  - This study aimed to clarify the histological characteristics related to
      preoperative chemotherapy for colorectal liver metastases (CRLM). Sixty-three
      patients with CRLM were divided into two groups: CRLM with chemotherapy (41
      cases, group A) and CRLM without chemotherapy (22 cases; surgical treatment
      alone, group S) to identify the histological differences associated with
      chemotherapy. In addition, we investigated the effects of combination
      chemotherapy on the histology of metastatic lesions. Infarct-like necrosis (ILN),
      three-zonal changes, and cholesterol clefts were more frequent in group A than in
      group S (P < 0.05). ILN and three-zonal changes were more common in the 5-FU with
      leucovorin and oxaliplatin (FOLFOX), or 5-FU with leucovorin and irinotecan
      (FOLFIRI) with or without additional bevacizumab groups than in group S (P <
      0.05). Cholesterol clefts in the FOLFOX or FOLFIRI with bevacizumab group and
      foamy macrophages in the FOLFOX or FOLFIRI group were more common than in group S
      (P < 0.05). Cases with more than three of the four histological findings--i.e.
      ILN, three-zonal changes, cholesterol clefts, and foamy macrophages--were more
      frequent in the FOLFOX or FOLFIRI with or without additional bevacizumab groups
      than in group S (P < 0.05). We showed histological findings for every
      representative chemotherapy regimen for CRLM to clarify the effects of
      preoperative chemotherapy.

PMID- 25940916
TI  - Hard machining, glaze firing and hydrofluoric acid etching: Do these procedures
      affect the flexural strength of a leucite glass-ceramic?
AB  - OBJECTIVE: To evaluate the effects of hard machining, glaze firing and
      hydrofluoric acid etching on the biaxial flexural strength and roughness of a
      CAD/CAM leucite glass-ceramic; to investigate if ceramic post-machining surface
      roughness is influenced by the machining order and by the pair of burs used for
      it. METHODS: A hundred forty four discs were machined by six nominally identical
      pairs of burs and divided into groups (n=24): (1) machining-M, (2) machining and
      glaze firing-MG, (3) machining and hydrofluoric acid etching-MA, (4) machining,
      glaze firing and hydrofluoric acid etching-MGA, (5) machining followed by
      polishing, as a control-MP, (6) machining, polishing and hydrofluoric acid
      etching-MPA. The roughness after each treatment (Ra and Rz) was measured. The
      discs were submitted to a piston-on-three ball flexure test (ISO 6872/2008) and
      strength data analyzed through Weibull statistics (95% CI). RESULTS: M resulted
      in lower characteristic strength (sigma0) (128.2MPa) than MP (177.2MPa). The
      glaze firing reduced sigma0 (109MPa), without affecting roughness. Hydrofluoric
      acid etching increased the roughness without affecting sigma0. Spearman's
      coefficient (rs) indicated strong and significant correlation between machining
      order and roughness (rsRa=-0.66; rsRz=-0.73). The ceramic post-machining surface
      roughness differed significantly according to the pair of burs employed (p<0.05).
      SIGNIFICANCE: hard machining and glaze firing reduced the leucite ceramic
      strength, while hydrofluoric acid etching did not affect the strength.
      Variability in the roughness might be expected after machining, since it was
      influenced by the machining order and by the bur pairing.

PMID- 25940917
TI  - Metal dicarboxylates: new anode materials for lithium-ion batteries with good
      cycling performance.
AB  - A simple and versatile method for the preparation of manganese coordination
      polymers [Mn(3,5-PDC).2H2O] (3,5-H2PDC = 3,5-pyridinedicarboxylic acid) and Mn
      2,5-furandicarboxylate which goes via a simple hydrothermal route is developed
      and the coordination polymers are tested as novel high-energy anode materials for
      lithium-ion batteries for the first time. [Mn(3,5-PDC).2H2O] shows a high
      discharge capacity of 583.9 mA h g(-1) for the fourth cycle between a 0.05-3.0 V
      voltage limit at a discharge current density of 100 mA g(-1). A reversible
      capacity of 554.0 mA h g(-1) is retained after 240 cycles with a capacity
      retention of 94.8% while Mn 2,5-furandicarboxylate shows a high discharge
      capacity of 467.3 mA h g(-1) for the second cycle and a reversible capacity of
      436.6 mA h g(-1) is retained after 206 cycles with a capacity retention of 93.4%.

PMID- 25940919
TI  - The role of wet wrap therapy in skin disorders - a literature review.
AB  - Wet wrap therapy, based on skin application of a double layer of tubular bandages
      or gauze with a moist first inner layer and a dry second outer layer, is utilized
      to treat various pruritic conditions, in particular severe and refractory atopic
      dermatitis. This review, by literature search, evaluates current knowledge about
      wet wrap therapy. Wet wrap therapy superimposed topical corticosteroids appears
      more efficient than emollients only, at least for short-time treatments. Despite
      higher efficacy, there is a tendency towards more frequent infections when
      topical corticosteroids are covered with wet wrap bandages compared to emollients
      only. While temporary suppression of hypothalamic-pituitary-adrenocortical-axis
      was seen due to systemic bioactivity of corticosteroids, no long-term observation
      studies on putative adverse effects were identified. One hypothesis suggests that
      wet wrap therapy may trigger increased lamellar body secretion resulting in
      recovery of the damaged intercellular lipid laminar structure. Otherwise, little
      investigation on mechanisms exists.

PMID- 25940918
TI  - Comparative genomics of Pseudomonas syringae pv. syringae strains B301D and HS191
      and insights into intrapathovar traits associated with plant pathogenesis.
AB  - Pseudomonas syringae pv. syringae is a common plant-associated bacterium that
      causes diseases of both monocot and dicot plants worldwide. To help delineate
      traits critical to adaptation and survival in the plant environment, we generated
      complete genome sequences of P. syringae pv. syringae strains B301D and HS191,
      which represent dicot and monocot strains with distinct host specificities.
      Intrapathovar comparisons of the B301D (6.09 Mb) and HS191 (5.95 Mb plus a 52 kb
      pCG131 plasmid) genomes to the previously sequenced B728a genome demonstrated
      that the shared genes encompass about 83% of each genome, and include genes for
      siderophore biosynthesis, osmotolerance, and extracellular polysaccharide
      production. Between 7% and 12% of the genes are unique among the genomes, and
      most of the unique gene regions carry transposons, phage elements, or IS elements
      associated with horizontal gene transfer. Differences are observed in the type
      III effector composition for the three strains that likely influences host range.
      The HS191 genome had the largest number at 25 of effector genes, and seven
      effector genes are specific to this monocot strain. Toxin production is another
      major trait associated with virulence of P. syringae pv. syringae, and HS191 is
      distinguished by genes for production of syringopeptin SP25 and mangotoxin.

PMID- 25940920
TI  - Intra-Aortic Balloon Pump Support in the Isolated Beating Porcine Heart in
      Nonischemic and Ischemic Pump Failure.
AB  - The blood pressure changes induced by the intra-aortic balloon pump (IABP) are
      expected to create clinical improvement in terms of coronary perfusion and
      myocardial oxygen consumption. However, the measured effects reported in
      literature are inconsistent. The aim of this study was to investigate the
      influence of ischemia on IABP efficacy in healthy hearts and in shock. Twelve
      slaughterhouse porcine hearts (hearts 1-12) were connected to an external
      circulatory system, while physiologic cardiac performance was restored. Different
      clinical scenarios, ranging from healthy to cardiogenic shock, were simulated by
      step-wise administration of negative inotropic drugs. In hearts 7-12, severe
      global myocardial ischemia superimposed upon the decreased contractile states was
      created. IABP support was applied in all hearts under all conditions. Without
      ischemia, the IABP induced a mild increase in coronary blood flow and cardiac
      output. These effects were strongly augmented in the presence of persisting
      ischemia, where coronary blood flow increased by 49 +/- 24% (P < 0.01) and
      cardiac output by 17 +/- 6% (P < 0.01) in case of severe pump failure. As
      expected, myocardial oxygen consumption increased in case of ischemia (21 +/-
      17%; P < 0.01), while it slightly decreased without (-3 +/- 6%; P < 0.01). In
      case of progressive pump failure due to persistent myocardial ischemia, the IABP
      increased hyperemic coronary blood flow and cardiac output significantly, and
      reversed the progressive hemodynamic deterioration within minutes. This suggests
      that IABP therapy in acute myocardial infarction is most effective in patients
      with viable myocardium, suffering from persistent myocardial ischemia, despite
      adequate epicardial reperfusion. 

PMID- 25940921
TI  - Dietary L-leucine supplementation enhances intestinal development in suckling
      piglets.
AB  - L-Leucine is a signaling amino acid in animal metabolism. It is unknown whether
      supplementing L-leucine to breast-fed neonates may enhance their small-intestinal
      development. This hypothesis was tested with a piglet model. Seven-day-old sow
      reared pigs with an average birth weight of 1.45 kg were assigned randomly to the
      control or leucine group (n = 30/group). Piglets in the leucine group were orally
      administrated with 1.4 g L-leucine/kg body weight, whereas piglets in the control
      group received isonitrogenous L-alanine, twice daily for 14 days. The
      supplemental L-leucine amounted to 200 % of L-leucine intake from sow's milk by 7
      day-old pigs. At the end of the 2-week experiment, tissue samples were collected
      for determining intestinal morphology, expression of genes for intestinal leucine
      transporters (real-time RT-PCR and western blot analysis), and plasma metabolites
      and hormones. L-leucine administration increased (P < 0.05) villus height in the
      duodenum, an elevated ratio of villus height to crypt depth in the duodenum and
      ileum, plasma concentrations of leucine, glutamine and asparagine, as well as
      body-weight gains. mRNA levels for L-leucine transporters (SLC6A14, SLC6A19 and
      SLC7A9) and the abundance of the ATB(0,+) protein were increased (P < 0.05) but
      those for SLC7A7 mRNA and the LAT2 protein were decreased (P < 0.05) in the
      jejunum of leucine-supplemented piglets, compared with the control. Plasma
      concentrations of ammonia, urea, triglycerides, and growth-related hormones did
      not differ between the control and leucine groups. Collectively, these results
      indicate that L-leucine supplementation improves intestinal development and whole
      body growth in suckling piglets with a normal birth weight.

PMID- 25940922
TI  - Taurine supplementation ameliorates glucose homeostasis, prevents insulin and
      glucagon hypersecretion, and controls beta, alpha, and delta-cell masses in
      genetic obese mice.
AB  - Taurine (Tau) regulates beta-cell function and glucose homeostasis under normal
      and diabetic conditions. Here, we assessed the effects of Tau supplementation
      upon glucose homeostasis and the morphophysiology of endocrine pancreas, in
      leptin-deficient obese (ob) mice. From weaning until 90-day-old, C57Bl/6 and ob
      mice received, or not, 5% Tau in drinking water (C, CT, ob and obT). Obese mice
      were hyperglycemic, glucose intolerant, insulin resistant, and exhibited higher
      hepatic glucose output. Tau supplementation did not prevent obesity, but
      ameliorated glucose homeostasis in obT. Islets from ob mice presented a higher
      glucose-induced intracellular Ca(2+) influx, NAD(P)H production and insulin
      release. Furthermore, alpha-cells from ob islets displayed a higher oscillatory
      Ca(2+) profile at low glucose concentrations, in association with glucagon
      hypersecretion. In Tau-supplemented ob mice, insulin and glucagon secretion was
      attenuated, while Ca(2+) influx tended to be normalized in beta-cells and Ca(2+)
      oscillations were increased in alpha-cells. Tau normalized the inhibitory action
      of somatostatin (SST) upon insulin release in the obT group. In these islets,
      expression of the glucagon, GLUT-2 and TRPM5 genes was also restored. Tau also
      enhanced MafA, Ngn3 and NeuroD mRNA levels in obT islets. Morphometric analysis
      demonstrated that the hypertrophy of ob islets tends to be normalized by Tau with
      reductions in islet and beta-cell masses, but enhanced delta-cell mass in obT.
      Our results indicate that Tau improves glucose homeostasis, regulating beta-,
      alpha-, and delta-cell morphophysiology in ob mice, indicating that Tau may be a
      potential therapeutic tool for the preservation of endocrine pancreatic function
      in obesity and diabetes.

PMID- 25940923
TI  - Risk factors: More data to encourage current cigarette smokers to quit.

PMID- 25940924
TI  - ACE2-angiotensin-(1-7)-Mas axis might be a promising therapeutic target for
      pulmonary arterial hypertension.

PMID- 25940925
TI  - Transplantation: Ex vivo perfusion of human hearts--implications for donor organ
      availability.

PMID- 25940927
TI  - Deciphering a nanocarbon-based artificial peroxidase: chemical identification of
      the catalytically active and substrate-binding sites on graphene quantum dots.
AB  - The design and construction of efficient artificial enzymes is highly desirable.
      Recent studies have demonstrated that a series of carbon nanomaterials possess
      intrinsic peroxidase activity. Among them, graphene quantum dots (GQDs) have a
      high enzymatic activity. However, the catalytic mechanism remains unclear.
      Therefore, in this report, we chose to decipher their peroxidase activity. By
      selectively deactivating the ketonic carbonyl, carboxylic, or hydroxy groups and
      investigating the catalytic activities of these GQD derivatives, we obtained
      evidence that the -C=O groups were the catalytically active sites, whereas the
      O=C-O- groups acted as substrate-binding sites, and -C-OH groups can inhibit the
      activity. These results were corroborated by theoretical studies. This work
      should not only enhance our understanding of nanocarbon-based artificial enzymes,
      but also facilitate the design and construction of other types of target-specific
      artificial enzymes.

PMID- 25940928
TI  - Development and validation of a real-time quantitative PCR assay to detect
      Xanthomonas axonopodis pv. allii from onion seed.
AB  - Bacterial blight of onion is an emerging disease threatening world onion
      production. The causal agent Xanthomonas axonopodis pv. allii is seed transmitted
      and a reliable and sensitive tool is needed to monitor seed exchanges. A triplex
      quantitative real-time PCR assay was developed targeting two X. axonopodis pv.
      allii-specific markers and an internal control chosen in 5.8S rRNA gene from
      Alliaceae. Amplification of at least one marker indicates the presence of the
      bacterium in seed extracts. This real-time PCR assay detected all the 79 X.
      axonopodis pv. allii strains tested and excluded 85.2% of the 135 non-target
      strains and particularly all 39 saprophytic and pathogenic bacteria associated
      with onion. Cross-reactions were mainly obtained for strains assigned to nine
      phylogenetically related X. axonopodis pathovars. The cycle cut-off was estimated
      statistically at 36.3 considering a risk of false positive of 1%. The limit of
      detection obtained in at least 95% of the time (LOD 95%) was 5*10(3) CFU/g
      (colony forming unit/g). The sensitivity threshold was found to be 1 infected
      seed in 32,790 seeds. This real-time PCR assay should be useful for preventing
      the long-distance spread of X. axonopodis pv. allii via contaminated seed lots
      and determining the epidemiology of the bacterium.

PMID- 25940926
TI  - Genotype-based clinical trials in cardiovascular disease.
AB  - Consensus practice guidelines and the implementation of clinical therapeutic
      advances are usually based on the results of large, randomized clinical trials
      (RCTs). However, RCTs generally inform us on an average treatment effect for a
      presumably homogeneous population, but therapeutic interventions rarely benefit
      the entire population targeted. Indeed, multiple RCTs have demonstrated that
      interindividual variability exists both in drug response and in the development
      of adverse effects. The field of pharmacogenomics promises to deliver the right
      drug to the right patient. Substantial progress has been made in this field, with
      advances in technology, statistical and computational methods, and the use of
      cell and animal model systems. However, clinical implementation of
      pharmacogenetic principles has been difficult because RCTs demonstrating benefit
      are lacking. For patients, the potential benefits of performing such trials
      include the individualization of therapy to maximize efficacy and minimize
      adverse effects. These trials would also enable investigators to reduce sample
      size and hence contain costs for trial sponsors. Multiple ethical, legal, and
      practical issues need to be considered for the conduct of genotype-based RCTs.
      Whether pre-emptive genotyping embedded in electronic health records will
      preclude the need for performing genotype-based RCTs remains to be seen. 

PMID- 25940929
TI  - MALDI-TOF mass spectrometry for early identification of bacteria grown in blood
      culture bottles.
AB  - This note reports an interesting way to rapidly identify bacteria grown from
      blood culture bottles. Chocolate agar plates were inoculated with 1 drop of the
      positive blood bottle medium. After a 3-hour incubation, the growth veil was
      submitted to MALDI-TOF mass spectrometry: 77% of the bacteria present have been
      correctly identified. 

PMID- 25940933
TI  - Efinaconazole topical solution, 10%: formulation development program of a new
      topical treatment of toenail onychomycosis.
AB  - Transungual drug delivery of antifungals is considered highly desirable to treat
      common nail disorders such as onychomycosis, due to localized effects, and
      improved adherence resulting from minimal systemic adverse events. However, the
      development of effective topical therapies has been hampered by poor nail
      penetration. An effective topical antifungal must permeate through, and under the
      dense keratinized nail plate to the site of infection in the nail bed and nail
      matrix. We present here the formulation development program to provide effective
      transungual and subungual delivery of efinaconazole, the first topical broad
      spectrum triazole specifically developed for onychomycosis treatment. We discuss
      the important aspects encompassing the formulation development program for
      efinaconazole topical solution, 10%, focusing on its solubility in a number of
      solvents, in vitro penetration through the nail, and in vivo efficacy.
      Efinaconazole topical solution, 10% is a stable, non-lacquer, antifungal with a
      unique combination of ingredients added to an alcohol-based formulation to
      provide low surface tension and good wetting properties. This low surface tension
      is believed to affect effective transungual delivery of efinaconazole and
      believed to provide a dual mode of delivery by accessing the nail bed by wicking
      into the space between the nail and nail plate.

PMID- 25940934
TI  - The Histone Deacetylase Inhibitor Valproic Acid Sensitizes Gemcitabine-Induced
      Cytotoxicity in Gemcitabine-Resistant Pancreatic Cancer Cells Possibly Through
      Inhibition of the DNA Repair Protein Gamma-H2AX.
AB  - BACKGROUND: Gemcitabine (GEM) remains a major chemotherapeutic drug for
      pancreatic cancer, but resistance to GEM has been a big problem, as its response
      rate has been decreasing year by year. METHODS: The effect of the histone
      deacetylase inhibitor (HDAI) valproic acid (VPA) was compared with tranilast and
      RI-1 as a combinatorial treatment with GEM in four pancreatic cancer cell lines,
      BxPC-3, PK45p, MiaPaCa-2 and PK59. Cell viability assays were carried out to
      check the cytotoxic effects, western blotting was carried out for DNA repair
      mechanisms, and localization was determined by immunofluorescence. RESULTS: The
      sensitization factors (i.e., the fold ratio of cell viability for GEM/GEM plus
      drug) reveal that VPA increases the cytotoxic sensitization to GEM at
      approximately 2.7-fold, 1.2-fold, 1.5-fold and 2.2-fold in BxPC-3, MiaPaCa-2, PK
      45p and PK-59 cell lines, respectively. Moreover, GEM induces activation of the
      DNA repair protein H2AX proportional to the dosage. Interestingly, however, this
      effect can be abrogated by VPA. CONCLUSIONS: These results indicate that VPA
      enhances GEM-induced cytotoxicity in GEM-resistant pancreatic cancer cells,
      possibly through inhibition of DNA damage signaling and repair. Our study
      suggests VPA as a potential therapeutic agent for combinatorial treatment with
      GEM in pancreatic cancer.

PMID- 25940935
TI  - Improving Prediabetes Screenings at Rural Missouri County Health Departments.
AB  - With prediabetes criteria expanding in recent years, nurses offering prediabetes
      screenings require updates to stay abreast of current clinical guidelines. This
      study looked to improve rural Missouri health department nurses' understanding of
      prediabetes, improve the identification of prediabetes at participating health
      departments, and educate the nurses on existing prediabetes guidelines. A
      convenience sample of twenty-two nurses from seven rural Missouri health
      departments participated. Nurses completed a demographic questionnaire and a
      prediabetes knowledge pre-test prior to the intervention. Seven to eight weeks
      post-intervention, the health department nurses completed the prediabetes post
      tests. A single live education session was conducted at each health department.
      Data from the pre- and post-tests was reviewed within three result categories.
      The overall, laboratory nursing knowledge, and general nursing knowledge
      divisions each showed statistically significant improvement with a p < 0.05. This
      study's post-test improvement in prediabetes knowledge replicates the usefulness
      of a simple, low cost educational update. Nurses improved the identification of
      prediabetes laboratory values on post-test data and showed an increase in overall
      prediabetes knowledge. A single and simple continuing education program is a
      useful tool for rural health nurses. 

PMID- 25940936
TI  - Differences in Treatment of Chlamydia trachomatis by Ambulatory Care Setting.
AB  - Chlamydia trachomatis (CT) is the most commonly reported sexually transmitted
      infection (STI) in the US and timely, correct treatment can reduce CT
      transmission and sequelae. Emergency departments (ED) are an important location
      for diagnosing STIs. This study compared recommended treatment of CT in EDs to
      treatment in physician offices. Five years of data (2006-2010) were analyzed from
      the National Ambulatory Medical Care Survey, and the National Hospital Ambulatory
      Medical Care Surveys (NHAMCS), including the Outpatient survey (NHAMCS-OPD) and
      Emergency Department survey (NHAMCS-ED). All visits with a CT diagnosis and those
      with a diagnosis of unspecified venereal disease were selected for analysis.
      Differences in receipt of recommended treatments were compared between visits to
      physician offices and emergency departments using Chi square tests and logistic
      regression models. During the 5 year period, approximately 3.2 million ambulatory
      care visits had diagnosed CT or an unspecified venereal disease. A greater
      proportion of visits to EDs received the recommended treatment for CT compared to
      visits to physician offices (66.1 vs. 44.9 %, p < .01). When controlling for
      patients' age, sex and race/ethnicity, those presenting to the ED with CT were
      more likely to receive the recommended antibiotic treatment than patients
      presenting to a physician's office (OR 2.16; 95 % CI 1.04-4.48). This effect was
      attenuated when further controlling for patients' expected source of payment.
      These analyses demonstrate differences in the treatment of CT by ambulatory care
      setting as well as opportunities for increasing use of recommended treatments for
      diagnosed cases of this important STI.

PMID- 25940937
TI  - Project FIT: A School, Community and Social Marketing Intervention Improves
      Healthy Eating Among Low-Income Elementary School Children.
AB  - Project FIT was a two-year multi-component nutrition and physical activity
      intervention delivered in ethnically-diverse low-income elementary schools in
      Grand Rapids, MI. This paper reports effects on children's nutrition outcomes and
      process evaluation of the school component. A quasi-experimental design was
      utilized. 3rd, 4th and 5th-grade students (Yr 1 baseline: N = 410; Yr 2 baseline:
      N = 405; age range: 7.5-12.6 years) were measured in the fall and spring over the
      two-year intervention. Ordinal logistic, mixed effect models and generalized
      estimating equations were fitted, and the robust standard errors were utilized.
      Primary outcomes favoring the intervention students were found regarding
      consumption of fruits, vegetables and whole grain bread during year 2. Process
      evaluation revealed that implementation of most intervention components increased
      during year 2. Project FIT resulted in small but beneficial effects on
      consumption of fruits, vegetables, and whole grain bread in ethnically diverse
      low-income elementary school children.

PMID- 25940938
TI  - Analysis of nicastrin gene phylogeny and expression in zebrafish.
AB  - NICASTRIN is a component of the aspartyl protease gamma-secretase complex which
      is involved in intramembranous cleavage of type I transmembrane proteins, notably
      the Notch receptor proteins and the AMYLOID BETA A4 PRECURSOR PROTEIN (APP). This
      study aimed to characterize the orthologue of the human NICASTRIN (NCSTN) gene in
      zebrafish, an advantageous model organism for the study of human disease.
      Zebrafish Nicastrin protein was predicted to possess the conserved glutamate 333
      residue and DYIGS motif of human NCSTN that are important for substrate
      recognition/processing in gamma-secretase. Quantitative real-time RT-PCR revealed
      the profile of relative zebrafish nicastrin (ncstn) transcript levels in embryos
      at different times during development and in adult tissues. The analysis of
      synteny conservation revealed local rearrangements of ncstn and another gene,
      mpz, relative to copa, and pex19. In situ hybridization showed higher relative
      levels of ncstn transcripts in the developing brain and otic vesicles of embryos
      at 24 and 48 h post fertilization, respectively. Our observations are consistent
      with a role for Ncstn protein in Notch signaling within the proliferative
      ventricular zone of the developing central nervous system. 

PMID- 25940939
TI  - Inverted critical adsorption of polyelectrolytes in confinement.
AB  - What are the fundamental laws for the adsorption of charged polymers onto
      oppositely charged surfaces, for convex, planar, and concave geometries? This
      question is at the heart of surface coating applications, various complex
      formation phenomena, as well as in the context of cellular and viral biophysics.
      It has been a long-standing challenge in theoretical polymer physics; for
      realistic systems the quantitative understanding is however often achievable only
      by computer simulations. In this study, we present the findings of such extensive
      Monte-Carlo in silico experiments for polymer-surface adsorption in confined
      domains. We study the inverted critical adsorption of finite-length
      polyelectrolytes in three fundamental geometries: planar slit, cylindrical pore,
      and spherical cavity. The scaling relations extracted from simulations for the
      critical surface charge density sigmac-defining the adsorption-desorption
      transition-are in excellent agreement with our analytical calculations based on
      the ground-state analysis of the Edwards equation. In particular, we confirm the
      magnitude and scaling of sigmac for the concave interfaces versus the Debye
      screening length 1/kappa and the extent of confinement a for these three
      interfaces for small kappaa values. For large kappaa the critical adsorption
      condition approaches the known planar limit. The transition between the two
      regimes takes place when the radius of surface curvature or half of the slit
      thickness a is of the order of 1/kappa. We also rationalize how sigmac(kappa)
      dependence gets modified for semi-flexible versus flexible chains under external
      confinement. We examine the implications of the chain length for critical
      adsorption-the effect often hard to tackle theoretically-putting an emphasis on
      polymers inside attractive spherical cavities. The applications of our findings
      to some biological systems are discussed, for instance the adsorption of nucleic
      acids onto the inner surfaces of cylindrical and spherical viral capsids. 

PMID- 25940941
TI  - The rise of stem cell toxicology.

PMID- 25940940
TI  - Goal linking and everyday worries in clinical work stress: A daily diary study.
AB  - OBJECTIVES: In this study, we tested whether high levels of daily worrying are
      associated with linking, a tendency to overvalue the attainment of specific lower
      level goals for attaining higher level goals, and more specifically the
      attainment of experiencing happiness. METHODS: Thirty-two patients suffering from
      work stress complaints and awaiting a stress management treatment and 31 healthy
      adults, who formed the comparison group, filled in a goal linking questionnaire
      and two widely used trait worry questionnaires. Subsequently, they reported the
      frequency and duration of worry during 14 consecutive days and nights. RESULTS:
      The patients suffering from work stress complaints scored higher on the linking
      questionnaire and worried almost twice as much as the healthy comparison group,
      especially during the night-time. Furthermore, goal linking was a stronger
      predictor of the frequency and duration of worry in daily life than the trait
      worry questionnaires and this was independent of the observed group differences
      in daily worry. CONCLUSIONS: These findings provide evidence that people who
      believe that their happiness is strongly dependent on the attainment of specific
      lower level goals worry frequently in daily life. Linking seems to be at least
      partly responsible for the excessive worry found in high work stress.
      PRACTITIONER POINTS: Worry is elevated in patients seeking professional help for
      work stress complaints, compared to healthy controls The higher levels of worry
      in the patient group were related to elevated tendencies to overvalue the
      attainment of specific lower level goals as a means to attain higher level goals
      ('linking'). It could be beneficial for high worriers to learn how to reduce
      linking tendencies. No strong inferences on the direction of the association
      between worry and linking can be made, as we relied on correlational data in
      which a linking questionnaire predicted worry in daily life.

PMID- 25940942
TI  - Prevalence and nature of dyspnea in patients with hereditary hemorrhagic
      telangiectasia (HHT).
AB  - BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a vascular disorder
      associated with pulmonary AVMs (PAVMs), present in about 30-50% of patients.
      Dyspnea is frequently reported by about one-half of patients with PAVMs and has
      been related to the degree of right to left shunting. However, many HHT patients
      with PAVMs remain asymptomatic and those without PAVMs have been observed to have
      dyspnea, the cause of which has not been characterized. The study objectives were
      to determine the prevalence of dyspnea and its etiology in the HHT population.
      METHODS: Retrospective review of over 1000 patients at an HHT Center of
      Excellence from 1997 to 2010. Patients were categorized as definite HHT if they
      met >=3 clinical diagnostic criteria or had a positive genetic diagnosis.
      Patients were unlikely to have HHT (non-HHT) if they had 1 or fewer diagnostic
      criteria. Data on dyspnea prevalence (MMRC >= 1), PAVMs, underlying cardio
      pulmonary disease, symptomatic liver venous malformations, anemia and obesity was
      reviewed. RESULTS: 506 patients were categorized as having HHT, of which 202
      (40%) had confirmed PAVMs. Dyspnea prevalence was 35% (178/506) vs. 18% (50/284,
      p < 0.0001) in the HHT and non-HHT patients, respectively. With multivariable
      logistic regression, the odds of dyspnea (MMRC >=1) was 3.45 (95% CI 2.08-5.71)
      with the presence of PAVMs in HHT patients. Other independent predictors of
      dyspnea were older age, underlying cardio-pulmonary disease, anemia, and obesity.
      CONCLUSION: Prevalence of dyspnea is significant, evident in about one-third of
      HHT patients, often associated with PAVMs. It is important to consider other
      etiologies for dyspnea when assessing patients with HHT.

PMID- 25940943
TI  - Hemagglutinin stem reactive antibody response in individuals immunized with a
      seasonal influenza trivalent vaccine.

PMID- 25940932
TI  - Women living with HIV still lack highly effective contraception: results from the
      ANRS VESPA2 study, France, 2011.
AB  - OBJECTIVES: Advances in antiretroviral treatment (ART) have led to improvements
      in reproductive health for women living with HIV. This paper aims to investigate
      the pattern of contraceptive use among women living with HIV in France. STUDY
      DESIGN: Data were drawn from the ANRS VESPA2 study, which included a
      representative sample of HIV-positive people. Contraception methods were
      documented, including condoms, highly effective contraception methods (HEC) and
      traditional methods. We measured the frequency of not using any modern
      contraception (neither condoms nor HEC) and of HEC use and studied their
      correlates (i.e., geographic origin, age, parity, partnership status, education
      level, material deprivation, employment status, health insurance, visits to a
      gynecologist, being on ART, cardiovascular risk) among women at risk of an
      unintended pregnancy. RESULTS: Of the 662 women of reproductive age, 327 were in
      need of contraception. Overall, 20.5% used HEC, 58.8% used condoms and 20.7% used
      traditional or no methods, with no difference according to geographic origin [sub
      Saharan African (SSA) women vs. French and other migrant women]. Among SSA women,
      being <30years old [odds ratio (OR) 16.39, 95% confidence interval (95%CI) 2.77
      97.01], having had at least one child (OR 3.75, 95%CI 1.75-8.04) and being
      employed (OR 2.36, 95%CI 0.99-5.61) were associated with HEC use; among French
      and other migrant women, HEC use was associated with being in a stable
      partnership (OR 4.5, 95%CI 1.2-17.2) and material deprivation (OR 3.3 95%CI 1.4
      9.8). Gynecologist visits, health insurance status and cardiovascular risk were
      not associated with HEC use. CONCLUSIONS: Condoms remained the predominant
      contraceptive method despite the absence of restrictions on hormonal
      contraception and intrauterine device use for HIV-positive women. The recent
      recommendations about dual method protection should be actively promoted,
      targeting HIV-positive women, HIV specialists and gynecologists to overcome the
      barriers to effective contraception. IMPLICATIONS: The information provided in
      this study constitutes a major contribution to comprehensively inform the
      scientific community on contraception practices among women living with HIV in
      France in the early 2010s. Our results show that the therapeutic advances since
      the late 1990s and the removal of restrictions on hormonal contraception use have
      not led to the expected shift in contraception patterns. There is an urgent need
      to promote dual method protection, as condom use may decrease in the future in
      the context of the preventive effect of ART.

PMID- 25940945
TI  - pH-Dependent Galvanic Replacement of Supported and Colloidal Cu2O Nanocrystals
      with Gold and Palladium.
AB  - Galvanic replacement reactions (GRRs) on nanoparticles (NPs) are typically
      performed between two metals, i.e., a solid metal NP and a replacing salt
      solution of a more noble metal. The solution pH in GRRs is commonly considered an
      irrelevant parameter. Yet, the solution pH plays a major role in GRRs involving
      metal oxide NPs. Here, Cu(2)O nanocrystals (NCs) are studied as galvanic
      replacement (GR) precursors, undergoing replacement by gold and palladium, with
      the resulting nanostructures showing a strong dependence on the pH of the
      replacing metal salt solution. GRRs are reported for the first time on supported
      (chemically deposited) oxide NCs and the results are compared with those obtained
      with corresponding colloidal systems. Control of the pH enables production of
      different nanostructures, from metal-decorated Cu(2)O NCs to uniformly coated
      Cu(2)O-in-metal (Cu(2)O@Me) core-shell nanoarchitectures. Improved metal
      nucleation efficiencies at low pHs are attributed to changes in the Cu(2)O
      surface charge resulting from protonation of the oxide surface. GR followed by
      etching of the Cu(2)O cores provides metal nanocages that collapse upon drying;
      the latter is prevented using a sol-gel silica overlayer stabilizing the metal
      nanocages. Metal-replaced Cu(2)O NCs and their corresponding stabilized
      nanostructures may be useful as photocatalysts, electrocatalysts, and
      nanosensors.

PMID- 25940946
TI  - Correlation Between Pneumocystis jirovecii Mitochondrial Genotypes and High and
      Low Fungal Loads Assessed by Single Nucleotide Primer Extension Assay and
      Quantitative Real-Time PCR.
AB  - We designed a single nucleotide primer extension (SNaPshot) assay for
      Pneumocystis jirovecii genotyping, targeting mt85 SNP of the mitochondrial large
      subunit ribosomal RNA locus, to improve minority allele detection. We then
      analyzed 133 consecutive bronchoalveolar lavage (BAL) fluids tested positive for
      P. jirovecii DNA by quantitative real-time PCR, obtained from two hospitals in
      different locations (Hospital 1 [n = 95] and Hospital 2 [n = 38]). We detected
      three different alleles, either singly (mt85C: 39.1%; mt85T: 24.1%; mt85A: 9.8%)
      or together (27%), and an association between P. jirovecii mt85 genotype and the
      patient's place of hospitalization (p = 0.011). The lowest fungal loads (median =
      0.82 * 10(3) copies/MUl; range: 15-11 * 10(3) ) were associated with mt85A and
      the highest (median = 1.4 * 10(6) copies/MUl; range: 17 * 10(3) -1.3 * 10(7) )
      with mt85CTA (p = 0.010). The ratios of the various alleles differed between the
      36 mixed-genotype samples. In tests of serial BALs (median: 20 d; range 4-525)
      from six patients with mixed genotypes, allele ratio changes were observed five
      times and genotype replacement once. Therefore, allele ratio changes seem more
      frequent than genotype replacement when using a SNaPshot assay more sensitive for
      detecting minority alleles than Sanger sequencing. Moreover, because microscopy
      detects only high fungal loads, the selection of microscopy-positive samples may
      miss genotypes associated with low loads.

PMID- 25940947
TI  - Identification and validation of a two-gene expression index for subtype
      classification and prognosis in Diffuse Large B-Cell Lymphoma.
AB  - The division of diffuse large B-cell lymphoma (DLBCL) into germinal center B-cell
      like (GCB) and activated B-cell-like (ABC) subtypes based on gene expression
      profiling has proved to be a landmark in understanding the pathogenesis of the
      disease. This study aims to identify a novel biomarker to facilitate the
      translation of research into clinical practice. Using a training set of 350
      patients, we identified a two-gene expression signature, "LIMD1-MYBL1 Index",
      which is significantly associated with cell-of-origin subtypes and clinical
      outcome. This two-gene index was further validated in two additional dataset.
      Tested against the gold standard method, the LIMD1-MYBL1 Index achieved 81%
      sensitivity, 89% specificity for ABC group and 81% sensitivity, 87% specificity
      for GCB group. The ABC group had significantly worse overall survival than the
      GCB group (hazard ratio = 3.5, P = 0.01). Furthermore, the performance of LIMD1
      MYBL1 Index was satisfactory compared with common immunohistochemical algorithms.
      Thus, the LIMD1-MYBL1 Index had considerable clinical value for DLBCL subtype
      classification and prognosis. Our results might prompt the further development of
      this two-gene index to a simple assay amenable to routine clinical practice.

PMID- 25940949
TI  - Introductory paragraph.

PMID- 25940948
TI  - Enterobacter asburiae KE17 association regulates physiological changes and
      mitigates the toxic effects of heavy metals in soybean.
AB  - This study aimed to elucidate the role played by Enterobacter asburiae KE17 in
      the growth and metabolism of soybeans during copper (100 MUm Cu) and zinc (100
      MUm Zn) toxicity. When compared to controls, plants grown under Cu and Zn stress
      exhibited significantly lower growth rates, but inoculation with E. asburiae KE17
      increased growth rates of stressed plants. The concentrations of plant hormones
      (abscisic acid and salicylic acid) and rates of lipid peroxidation were higher in
      plants under heavy metal stress, while total chlorophyll, carotenoid content and
      total polyphenol concentration were lower. While the bacterial treatment reduced
      the abscisic acid and salicylic acid content and lipid peroxidation rate of Cu
      stressed plants, it also increased the concentration of photosynthetic pigments
      and total polyphenol. Moreover, the heavy metals induced increased accumulation
      of free amino acids such as aspartic acid, threonine, serine, glycine, alanine,
      leucine, isoleucine, tyrosine, proline and gamma-aminobutyric acid, while E.
      asburiae KE17 significantly reduced concentrations of free amino acids in metal
      affected plants. Co-treatment with E. asburiae KE17 regulated nutrient uptake by
      enhancing nitrogen content and inhibiting Cu and Zn accumulation in soybean
      plants. The results of this study suggest that E. asburiae KE17 mitigates the
      effects of Cu and Zn stress by reprogramming plant metabolic processes.

PMID- 25940950
TI  - Changing Trends in, and Characteristics Associated with, Not Undergoing Cardiac
      Catheterization in Elderly Adults Hospitalized with ST-Segment Elevation Acute
      Myocardial Infarction.
AB  - OBJECTIVES: To describe decade- long trends (1999-2009) in the rates of not
      undergoing cardiac catheterization and percutaneous coronary intervention (PCI)
      in individuals aged 65 and older presenting with an ST-segment elevation acute
      myocardial infarction (STEMI) and factors associated with not undergoing these
      procedures. DESIGN: Observational population-based study. SETTING: Worcester,
      Massachusetts, metropolitan area. PARTICIPANTS: Individuals aged 65 and older
      hospitalized for an STEMI in six biennial periods between 1999 and 2009 at 11
      central Massachusetts medical centers (N=960). MEASUREMENTS: Analyses were
      conducted to examine the characteristics of people who did not undergo cardiac
      catheterization overall and stratified into two age strata (65-74, >=75).
      RESULTS: Between 1999 and 2009, dramatic declines (from 59.4% to 7.5%) were
      observed in the proportion of older adults who did not undergo cardiac
      catheterization at all greater Worcester hospitals. These declines were observed
      in individuals aged 65 to 74 (58.4-6.7%) and in those aged 75 and older (69.4
      13.5%). The proportion of individuals not undergoing PCI after undergoing cardiac
      catheterization decreased from 36.6% in 1999 to 6.5% in 2009. Women, individuals
      with a prior MI, those with do-not-resuscitate orders, and those with various
      comorbidities were less likely to have undergone these procedures than comparison
      groups. CONCLUSION: Older adults who develop an STEMI are increasingly likely to
      undergo cardiac catheterization and PCI, but several high-risk groups remain less
      likely to undergo these procedures.

PMID- 25940951
TI  - Schistosoma mansoni and HIV acquisition in fishing communities of Lake Victoria,
      Uganda: a nested case-control study.
AB  - OBJECTIVE: It has been suggested that Schistosoma mansoni, which is endemic in
      African fishing communities, might increase susceptibility to human
      immunodeficiency virus (HIV) acquisition. If confirmed, this would be of great
      public health importance in these high HIV-risk communities. This study was
      undertaken to determine whether S. mansoni infection is a risk factor for HIV
      infection among the fishing communities of Lake Victoria, Uganda. We conducted a
      matched case-control study, nested within a prospective HIV incidence cohort,
      including 50 HIV seroconverters (cases) and 150 controls during 2009-2011.
      METHODS: S. mansoni infection prior to HIV seroconversion was determined by
      measuring serum circulating anodic antigen (CAA) in stored serum. HIV testing was
      carried out using the Determine rapid test and infection confirmed by enzyme
      linked immunosorbent assays. RESULTS: About 49% of cases and 52% of controls had
      S. mansoni infection prior to HIV seroconversion (or at the time of a similar
      study visit, for controls): odds ratio, adjusting for ethnicity, religion,
      marital status, education, occupation, frequency of alcohol consumption in
      previous 3 months, number of sexual partners while drunk, duration of stay in the
      community, and history of schistosomiasis treatment in the past 2 years was 1.23
      (95% CI 0.3-5.7) P = 0.79. S. mansoni infections were chronic (with little change
      in status between enrolment and HIV seroconversion), and there was no difference
      in median CAA concentration between cases and controls. CONCLUSIONS: These
      results do not support the hypothesis that S. mansoni infection promotes HIV
      acquisition.

PMID- 25940953
TI  - Proximity to blue spaces and risk of infection with Pseudomonas aeruginosa in
      cystic fibrosis: A case-control analysis.
AB  - BACKGROUND: The acquisition of Pseudomonas aeruginosa in cystic fibrosis (CF) is
      associated with lower survival, decreased lung function, worse radiological
      scores, increased exacerbations and reduced nutritional status. Open water is a
      known reservoir and a potential source of exposure to P. aeruginosa. METHODS:
      Twenty eight adult CF patients who had no history of P. aeruginosa and had
      negative P. aeruginosa IgG antibody levels, were matched by age and sex with 28
      CF patients with chronic P. aeruginosa colonization. Straight line and closest
      walking distance from patient's residence to the nearest "blue space", i.e.
      surface water as determined by Google Earth, were compared between the two
      groups, and odds ratios (OR) were estimated using conditional logistic
      regression. RESULTS: Patients who were never infected with P. aeruginosa lived
      significantly further away from a natural water source than P. aeruginosa
      colonized patients, both when considering shortest walking distance (mean 487 m
      vs 308 m, p=0.014) and beeline (mean 324 m vs 202 m, p=0.021). Conditional
      logistic regression (correcting for FEV1%) revealed ORs for chronic P. aeruginosa
      colonization of 0.35 (95% CI 0.13-0.98; p=0.045) and 0.12 (95% CI 0.02-0.81;
      p=0.028) for each doubling in the beeline or walking distance, respectively,
      between residence and open water. CONCLUSION: We discovered that adult CF
      patients without P. aeruginosa infection live significantly further from blue
      space than CF patients with chronic P. aeruginosa colonization. Within the
      limitations of a case-control study, this may indicate that natural open water
      represents a source of infection by P. aeruginosa in CF. REGISTRATION: The study
      was approved by the local ethical committee of the UZ Leuven, Belgium (ML-5028).

PMID- 25940952
TI  - A de novo 0.63 Mb 6q25.1 deletion associated with growth failure, congenital
      heart defect, underdeveloped cerebellar vermis, abnormal cutaneous elasticity and
      joint laxity.
AB  - Deletions of the long arm of chromosome 6 are rare and are characterized by great
      clinical variability according to the deletion breakpoint. We report a on 6-year
      old girl with a de novo 0.63 Mb deletion on chromosome 6q25.1 who demonstrated
      multiple congenital anomalies including a ventricular septal defect and an
      underdeveloped cerebellar vermis. She presented with severe pre- and post-natal
      growth failure, hyperextensible small joints (Beighton scores = 8/9; with normal
      parental scores), and an abnormally elastic, redundant skin. Abnormally high
      upper/lower segment ratio (i.e., 1.34 = > 3SD), mild dysmorphic facial features
      and developmental delay were also present. The girl's phenotype was compared
      with: (i) two girls, each previously reported by Bisgaard et al. and Caselli et
      al. with similar albeit larger (2.6-7.21 Mb) deletions; (ii) seven additional
      individuals (6 M; 1 F) harboring deletions within the 6q25.1 region reported in
      the literature; and (iii) ten further patients (5 M; 4 F; 1 unrecorded sex)
      recorded in the DECIPHER 6.0 database. We reported on the present girl as her
      findings could contribute to advance the phenotype of 6q deletions. In addition,
      the present deletion is the smallest so far recorded in the 6q25 region
      encompassing eight known genes [vs. 41 of Bisgaard et al., and 23 of Caselli et
      al.,], including the TAB2 (likely responsible for the girl's congenital heart
      defect), LATS1 gene, and the UST gene (a regulator of the homeostasis of
      proteoglycans, which could have played a role in the abnormal dermal and
      cartilage elasticity).

PMID- 25940955
TI  - Structural aspects of phenylglycines, their biosynthesis and occurrence in
      peptide natural products.
AB  - Phenylglycine-type amino acids occur in a wide variety of peptide natural
      products, including glycopeptide antibiotics and biologically active linear and
      cyclic peptides. Sequencing of biosynthesis gene clusters of chloroeremomycin,
      balhimycin and pristinamycin paved the way for intensive investigations on the
      biosynthesis of 4-hydroxyphenylglycine (Hpg), 3,5-dihydroxyphenylglycine (Dpg)
      and phenylglycine (Phg) in recent years. The significance and importance of this
      type of unusual non-proteinogenic aromatic amino acids also for medicinal
      chemistry has drawn the attention of many research groups and pharmaceutical
      companies. Herein structures and properties of phenylglycine containing natural
      products as well as the biosynthetic origin and incorporation of phenylglycines
      are discussed.

PMID- 25940954
TI  - Widening the circle of security: a quasi-experimental evaluation of attachment
      based professional development for family child care providers.
AB  - This pilot program evaluation was undertaken to examine the effectiveness of an
      attachment-based, group professional-development experience, Circle of Security
      Parenting, on family childcare (FCC) providers' psychological resources and self
      efficacy in managing children's challenging behaviors and supporting children's
      socioemotional development. Licensed FCC providers with children actively in
      their care (n = 34) self-selected into the program, offered in English and
      Spanish through a regional support network for FCC providers; a comparison group
      of providers was recruited from the state database of licensed providers (n =
      17). A significant Time * Group interaction was observed for self-efficacy in
      managing challenging behaviors, F(1, 46) = 30.59, p = .000, partial eta(2) = .40,
      with participating providers' mean self-efficacy scores increasing, p = .000, d =
      .78, while comparison providers' decreased, p = .003, d = 1.40. Mean depressive
      symptoms decreased over time for both groups whereas job stress-related resources
      were stable over time in both groups. Patterns of association were found between
      providers' self-report of difficulties considering children's mental states and
      depressive symptoms, job stress resources, and self-efficacy. Limitations and
      implications for future research are reviewed, including the impact of conducting
      this work within an organized support network for FCC providers. 

PMID- 25940956
TI  - Lack of TNF-alpha receptor type 2 protects motor neurons in a cellular model of
      amyotrophic lateral sclerosis and in mutant SOD1 mice but does not affect disease
      progression.
AB  - Changes in the homeostasis of tumor necrosis factor alpha (TNFalpha) have been
      demonstrated in patients and experimental models of amyotrophic lateral sclerosis
      (ALS). However, the contribution of TNFalpha to the development of ALS is still
      debated. TNFalpha is expressed by glia and neurons and acts through the membrane
      receptors TNFR1 and TNFR2, which may have opposite effects in neurodegeneration.
      We investigated the role of TNFalpha and its receptors in the selective motor
      neuron death in ALS in vitro and in vivo. TNFR2 expressed by astrocytes and
      neurons, but not TNFR1, was implicated in motor neuron loss in primary SOD1-G93A
      co-cultures. Deleting TNFR2 from SOD1-G93A mice, there was partial but
      significant protection of spinal motor neurons, sciatic nerves, and tibialis
      muscles. However, no improvement of motor impairment or survival was observed.
      Since the sciatic nerves of SOD1-G93A/TNFR2-/- mice showed high phospho-TAR DNA
      binding protein 43 (TDP-43) accumulation and low levels of acetyl-tubulin, two
      indices of axonal dysfunction, the lack of symptom improvement in these mice
      might be due to impaired function of rescued motor neurons. These results
      indicate the interaction between TNFR2 and membrane-bound TNFalpha as an
      innovative pathway involved in motor neuron death. Nevertheless, its inhibition
      is not sufficient to stop disease progression in ALS mice, underlining the
      complexity of this pathology. We show evidence of the involvement of neuronal and
      astroglial TNFR2 in the motor neuron degeneration in ALS. Both concur to cause
      motor neuron death in primary astrocyte/spinal neuron co-cultures. TNFR2 deletion
      partially protects motor neurons and sciatic nerves in SOD1-G93A mice but does
      not improve their symptoms and survival. However, TNFR2 could be a new target for
      multi-intervention therapies. 

PMID- 25940957
TI  - Polycation-sodium lauryl ether sulfate-type surfactant complexes: influence of
      ethylene oxide length.
AB  - Polyelectrolyte-surfactant complexes (PESC) are a class of materials which form
      spontaneously by self-assembly driven by electrostatic and hydrophobic
      interactions. PESC containing sodium lauryl ether sulfates (SLES) have found wide
      application in hair care products like shampoo. Typically, SLES with only one or
      two ethylene oxide (EO) groups are used for this application. We have studied the
      influence of the size of the EO block (ranging from 0 to 30 EO groups) on
      complexation with two model polycations: linear polyDADMAC and branched PEI. PESC
      size and electrostatic properties were determined during stepwise titration of
      buffered polycation solutions. The critical aggregation concentration (CAC) of
      PESC was determined by surface tension measurements and fluorescence
      spectroscopy. For polyDADMAC, there is no influence of the size of the EO block
      on the complexation behavior; the stiff polycation governs the structure
      formation. For PEI, it was seen that the EO block size does affect the structure
      of the complexes. The CAC value of the investigated complexes turns out to be
      rather independent of the EO block size; however, the CMC/CAC ratio decreases
      with increasing size of the EO block. This latter observation explains why the
      Lochhead-Goddard effect is most effective for small EO blocks. 

PMID- 25940959
TI  - Oclacitinib in feline nonflea-, nonfood-induced hypersensitivity dermatitis:
      results of a small prospective pilot study of client-owned cats.
AB  - BACKGROUND: Oclacitinib is a Janus kinase inhibitor that decreases pruritus and
      lesions in allergic dogs. In cats, it is able to inhibit interleukin-31-induced
      pruritus; no information is available on its clinical effectiveness.
      HYPOTHESIS/OBJECTIVES: To evaluate the efficacy, ease of administration and
      tolerability of oclacitinib in feline nonflea-, nonfood-induced hypersensitivity
      dermatitis. METHODS: Cats >12 months of age and >3 kg body weight with a
      diagnosis of nonflea-, nonfood-induced hypersensitivity dermatitis were treated
      with oclacitinib, 0.4-0.6 mg/kg orally (p.o.) twice daily for 2 weeks, then once
      daily for an additional 14 days. Clinical lesions were evaluated with the Scoring
      Feline Allergic Dermatitis (SCORFAD) system and pruritus was evaluated with a 10
      cm-long visual analog scale (VAS) before and at the end of the study. Owners
      assessed global efficacy, ease of administration and tolerability with a four
      point scale. RESULTS: Twelve cats were treated with a mean initial oclacitinib
      dose of 0.47 mg/kg p.o. twice daily. There was good improvement in SCORFAD and
      VAS pruritus scores in five of 12 cases, while the other cats were unchanged,
      deteriorated or dropped out due to treatment failure. Owners scored global
      efficacy as good/excellent in four of 12 cases and ease of administration and
      tolerability as good/excellent in 10 of 12. CONCLUSIONS AND CLINICAL IMPORTANCE:
      Oclacitinib at 0.4-0.6 mg/kg p.o. may be an effective and safe drug for some cats
      with nonflea-, nonfood-induced hypersensitivity dermatitis. Further studies are
      needed to identify the most effective dose range for this species.

PMID- 25940958
TI  - Mitochondrial biogenesis is impaired in osteoarthritis chondrocytes but
      reversible via peroxisome proliferator-activated receptor gamma coactivator
      1alpha.
AB  - OBJECTIVE: The etiology of chondrocyte mitochondrial dysfunction in
      osteoarthritis (OA) is not completely understood. OA chondrocytes are deficient
      in the metabolic biosensors active AMP-activated protein kinase (AMPK) and
      sirtuin 1 (SIRT-1), which modulate the mitochondrial biogenesis "master
      regulator" peroxisome proliferator-activated receptor gamma coactivator 1alpha
      (PGC-1alpha). Moreover, PGC-1alpha critically mediates AMPK anticatabolic
      activity in chondrocytes. The aim of this study was to test the hypothesis that
      mitochondrial biogenesis is deficient in human OA chondrocytes and that this
      deficiency functionally increases chondrocyte procatabolic responses, which are
      reversed by activation of the AMPK/SIRT-1/PGC-1alpha pathway. METHODS: We
      assessed the expression and activity (phosphorylation) of AMPKalpha, SIRT-1, and
      PGC-1alpha in human knee chondrocytes and human and mouse knee cartilage, and we
      defined and compared the content and function of mitochondria, including
      oxidative phosphorylation and expression of mitochondrial biogenesis factors
      (mitochondrial transcriptional factor A [TFAM] and nuclear respiratory factors
      [NRFs]). RESULTS: Human knee OA chondrocytes had a decreased mitochondrial
      biogenesis capacity, which was linked to reduced AMPKalpha activity and decreased
      expression of SIRT-1, PGC-1alpha, TFAM, NRF-1, and NRF-2. Human knee OA and aging
      mouse knee cartilage had decreased expression of TFAM and ubiquinol-cytochrome c
      reductase core protein, a subunit of mitochondrial complex III, in situ.
      Chondrocyte TFAM knockdown inhibited mitochondrial biogenesis and enhanced
      procatabolic responses to interleukin-1beta. Finally, activation of AMPK by A
      769662 increased PGC-1alpha expression via SIRT-1 and reversed impairments in
      mitochondrial biogenesis, oxidative phosphorylation, and intracellular ATP in
      human knee OA chondrocytes. CONCLUSION: Mitochondrial biogenesis is deficient in
      human OA chondrocytes, and this deficiency promotes chondrocyte procatabolic
      responses. TFAM-mediated activation of the AMPK/SIRT-1/PGC-1alpha pathway
      reverses these effects, suggesting translational potential of pharmacologic AMPK
      activators to limit OA progression.

PMID- 25940960
TI  - The TaDREB3 transgene transferred by conventional crossings to different genetic
      backgrounds of bread wheat improves drought tolerance.
AB  - Drought tolerance of the wheat cultivar Bobwhite was previously enhanced by
      transformation with a construct containing the wheat DREB3 gene driven by the
      stress-inducible maize Rab17 promoter. Progeny of a single T2 transgenic line
      were used as pollinators in crosses with four elite bread wheat cultivars from
      Western Australia: Bonnie Rock, IGW-2971, Magenta and Wyalkatchem, with the aim
      of evaluating transgene performance in different genetic backgrounds. The
      selected pollinator line, BW8-9-10-3, contained multiple transgene copies, had
      significantly improved drought tolerance compared with wild-type plants and
      showed no growth and development penalties or abnormalities. A single hybrid
      plant was selected from each cross-combination for three rounds of backcrossing
      with the corresponding maternal wheat cultivar. The transgene was detected in all
      four F1 BC3 combinations, but stress-inducible transgene expression was found in
      only three of the four combinations. Under well-watered conditions, the
      phenotypes and grain yield components of the F2 BC3 transgene-expressing lines
      were similar to those of corresponding recurrent parents and null-segregants.
      Under severe drought conditions, the backcross lines demonstrated 12-18% higher
      survival rates than the corresponding control plants. Two from four F3 BC3
      transgenic lines showed significantly higher yield (18.9% and 21.5%) than control
      plants under limited water conditions. There was no induction of transgene
      expression under cold stress, and therefore, no improvement of frost tolerance
      observed in the progenies of drought-tolerant F3 BC3 lines. 

PMID- 25940961
TI  - Conformational analysis of N,N,N-Trimethyl-(3,3-dimethylbutyl)ammonium iodide by
      NMR spectroscopy: a sterically hindered trans-standard.
AB  - A predominantly trans-1,2-disubstituted ethane system - N,N,N-trimethyl-(3,3
      dimethylbutyl)ammonium iodide - is of particular interest for conformational
      analysis, because it contains both an organic and a highly polar substituent,
      making it soluble and thus applicable to study in a large variety of solvents.
      The fraction of the trans conformer of this molecule in a wide range of protic
      and aprotic solvents was determined by the nuclear magnetic resonance proton
      couplings to be approximately 90%, in contrast to the previously assumed 100%.
      The consistently strong preference of the trans conformation should establish
      N,N,N-trimethyl-(3,3-dimethylbutyl)ammonium iodide as a possibly useful 'trans
      standard' in conformational analysis, much more so than 1,2-ditert-butylethane,
      which has a poor solubility in many solvents.

PMID- 25940962
TI  - Adverse Geriatric Outcomes Secondary to Polypharmacy in a Mouse Model: The
      Influence of Aging.
AB  - We aimed to develop a mouse model of polypharmacy, primarily to establish whether
      short-term exposure to polypharmacy causes adverse geriatric outcomes. We also
      investigated whether old age increased susceptibility to any adverse geriatric
      outcomes of polypharmacy. Young (n= 10) and old (n= 21) male C57BL/6 mice were
      administered control diet or polypharmacy diet containing therapeutic doses of
      five commonly used medicines (simvastatin, metoprolol, omeprazole, acetaminophen,
      and citalopram). Mice were assessed before and after the 2- to 4-week
      intervention. Over the intervention period, we observed no mortality and no
      change in food intake, body weight, or serum biochemistry in any age or treatment
      group. In old mice, polypharmacy caused significant declines in locomotor
      activity (pre minus postintervention values in control 2 +/- 13 counts,
      polypharmacy 32 +/- 7 counts,p< .05) and front paw wire holding impulse (control 
      2.45 +/- 1.02 N s, polypharmacy +1.99 +/- 1.19 N s,p< .05), loss of improvement
      in rotarod latency (control -59 +/- 11 s, polypharmacy -1.7 +/- 17 s,p< .05), and
      lowered blood pressure (control -0.2 +/- 3 mmHg, polypharmacy 11 +/- 4 mmHg,p<
      .05). In young mice, changes in outcomes over the intervention period did not
      differ between control and polypharmacy groups. This novel model of polypharmacy
      is feasible. Even short-term polypharmacy impairs mobility, balance, and strength
      in old male mice.

PMID- 25940963
TI  - Prognostication of post-cardiac arrest coma: early clinical and
      electroencephalographic predictors of outcome.
AB  - PURPOSE: To determine the temporal evolution, clinical correlates, and prognostic
      significance of electroencephalographic (EEG) patterns in post-cardiac arrest
      comatose patients treated with hypothermia. METHODS: Prospective cohort study of
      consecutive post-anoxic patients receiving hypothermia and continuous EEG
      monitoring between May 2011 and June 2014 (n = 100). In addition to clinical
      variables, 5-min EEG clips at 6, 12, 24, 48, and 72 h after return of spontaneous
      circulation (ROSC) were reviewed. EEG background was classified according to the
      American Clinical Neurophysiological Society critical care EEG terminology.
      Clinical outcome at discharge was dichotomized as good [Glasgow outcome scale
      (GOS) 4-5, low to moderate disability] vs. poor (GOS 1-3, severe disability to
      death). RESULTS: Non-ventricular fibrillation/tachycardia arrest, longer time to
      ROSC, absence of brainstem reflexes, extensor or no motor response, lower pH,
      higher lactate, hypotension requiring >2 vasopressors, and absence of reactivity
      on EEG were all associated with poor outcome (all p values <= 0.01). Suppression
      burst at any time indicated a poor prognosis, with a 0% false positive rate (FPR)
      [95% confidence interval (CI) 0-10%]. All patients (54/54) with suppression-burst
      or a low voltage (<20 uV) EEG at 24 h had a poor outcome, with an FPR of 0% [95%
      CI 0-8%]. Normal background voltage >= 20 uV without epileptiform discharges at
      any time interval carried a positive predictive value >70% for good outcome.
      CONCLUSIONS: Suppression-burst or a low voltage at 24 h after ROSC was not
      compatible with good outcome in this series. Normal background voltage without
      epileptiform discharges predicted a good outcome.

PMID- 25940964
TI  - Pneumocystis jirovecii airborne transmission between critically ill patients and
      health care workers.

PMID- 25940965
TI  - A neurofeedback-based intervention to reduce post-operative pain in lung cancer
      patients: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Thoracic surgery appears to be the treatment of choice for many lung
      cancers. Nevertheless, depending on the type of surgery, the chest area may be
      painful for several weeks to months after surgery. This painful state has
      multiple physical and psychological implications, including respiratory failure,
      inability to clear secretions by coughing, and even anxiety and depression that
      have negative effects on recovery. OBJECTIVE: The aim of this study is to
      evaluate the effect of a neurofeedback-based intervention on controlling acute
      post-surgery pain and improving long-term recovery in patients who undergo
      thoracotomy for lung resection for non-small cell lung cancer (NSCLC) at an
      academic oncologic hospital. METHODS: This study will be based on a 2-parallel
      group randomized controlled trial design, intervention versus usual care, with
      multiple in-hospital assessments and 2 clinical, radiological, and quality of
      life follow-ups. Participants will be randomized to either the intervention group
      receiving a neurofeedback-based relaxation training and usual care, or to a
      control group receiving only usual care. Pain intensity is the primary outcome
      and will be assessed using the Numeric Pain Rating Scale (NRS) in the days
      following the operation. Secondary outcomes will include the effect of the
      intervention on hospital utilization for pain crisis, daily opioid consumption,
      anxiety, patient engagement, blood test and chest x-ray results, and long-term
      clinical, radiological, and quality of life evaluations. Outcome measures will be
      repeatedly taken during hospitalization, while follow-up assessments will
      coincide with the follow-up visits. Pain intensity will be assessed by mixed
      model repeated analysis. Effect sizes will be calculated as mean group
      differences with standard deviations. RESULTS: We expect to have results for this
      study before the end of 2016. CONCLUSIONS: The proposed innovative, neurofeedback
      and relaxation-based approach to support post-surgery pain management could lead
      to significant improvements in patient short and long-term outcomes.

PMID- 25940967
TI  - Mesenteric venous thrombosis.

PMID- 25940968
TI  - ECG Response: May 5, 2015. Complete heart block. An escape ventricular rhythm.

PMID- 25940966
TI  - Contemporary cardiac issues in Duchenne muscular dystrophy. Working Group of the
      National Heart, Lung, and Blood Institute in collaboration with Parent Project
      Muscular Dystrophy.

PMID- 25940969
TI  - Excess anterior mitral leaflet in a patient with hypertrophic obstructive
      cardiomyopathy and systolic anterior motion.

PMID- 25940970
TI  - Letter by Stollberger and Finsterer regarding article, "Reversible de novo left
      ventricular trabeculations in pregnant women: implications for the diagnosis of
      left ventricular noncompaction in low-risk populations".

PMID- 25940971
TI  - Response to letter regarding article, "Reversible de novo left ventricular
      trabeculations in pregnant women: implications for the diagnosis of left
      ventricular noncompaction in low-risk populations".

PMID- 25940972
TI  - Letter from Le May and Cariou regarding article, "Proprotein convertase
      subtilisin kexin type 9 promotes intestinal overproduction of triglyceride-rich
      apolipoprotein B lipoproteins through both low-density lipoprotein receptor
      dependent and -independent mechanisms".

PMID- 25940974
TI  - Correction.

PMID- 25940973
TI  - Response to letter regarding article, "Proprotein convertase subtilisin kexin
      type 9 promotes intestinal overproduction of triglyceride-rich apolipoprotein B
      lipoproteins through both low-density lipoprotein receptor-dependent and 
      independent mechanisms".

PMID- 25940975
TI  - Improved outcomes for emergency department patients whose ambulance off-stretcher
      time is not delayed.
AB  - OBJECTIVE: To describe and compare characteristics and outcomes of patients who
      arrive by ambulance to the ED. We aimed to (i) compare patients with a delayed
      ambulance offload time (AOT) >30 min with those who were not delayed; and (ii)
      identify predictors of an ED length of stay (LOS) of >4 h for ambulance-arriving
      patients. METHODS: A retrospective, multi-site cohort study was undertaken in
      Australia using 12 months of linked health data (September 2007-2008). Outcomes
      of AOT delayed and non-delayed presentations were compared. Logistic regression
      analysis was undertaken to identify predictors of an ED LOS of >4 h. RESULTS: Of
      the 40 783 linked, analysable ambulance presentations, AOT delay of >30 min was
      experienced by 15%, and 63% had an ED LOS of >4 h. Patients with an AOT <30 min
      had better outcomes for: time to triage; ambulance time at hospital; time to see
      healthcare professional; proportion seen within recommended triage time frame;
      and ED LOS for both admitted and non-admitted patients. In-hospital mortality did
      not differ. Strong predictors of an ED LOS >4 h included: hospital admission,
      older age, triage category, and offload delay >30 min. CONCLUSION: Patients
      arriving to the ED via ambulance and offloaded within 30 min experience better
      outcomes than those delayed. Given that offload delay is a modifiable predictor
      of an ED LOS of >4 h, targeted improvements in the ED arrival process for
      ambulance patients might be useful.

PMID- 25940976
TI  - Anorectal dysfunction in patients with ulcerative colitis: impaired adaptation or
      enhanced perception?
AB  - BACKGROUND: Rectal disorders during ulcerative colitis (UC) drastically alter the
      quality of life and may result from an impairment of rectal perception and
      compliance. This study aims to assess anorectal disorders in patients with mild
      to-moderate UC. METHODS: Anal pressures and the rectal responses to phasic rectal
      isobaric distension in 10 patients with mild-to-moderate UC were prospectively
      compared with those in 10 healthy volunteers (HVs). KEY RESULTS: The patients in
      each group were similar regarding age, gender, and delivery. In the resting
      state, the anal canal pressures were similar between the groups. Only the squeeze
      pressures of the lower anal canal were significantly lower in UC patients than in
      HVs. During phasic isobaric distension, rectal sensitivity was similar between
      the groups, whatever the step of distension. Isobaric rectal distension resulted
      in a significant decrease of the rectoanal inhibitory reflex and a decrease in
      rectal tone and a significant drop in rectal compliance in UC patients compared
      with HVs. CONCLUSIONS & INFERENCES: Patients showing mild-to-moderate UC
      experience rectal compliance and innervation disorders without a significant
      change in rectal sensitivity. The findings of this work suggest impairment not
      only of the properties of the rectal wall but also of intrinsic innervation.
      Repeated evaluation over time may be helpful for analyzing the reversibility of
      the process after healing.

PMID- 25940978
TI  - Gene expression changes in residual advanced cervical cancer after radiotherapy:
      indicators of poor prognosis and radioresistance?
AB  - BACKGROUND: Different sensitivity of advanced cervical cancer to irradiation can
      decrease effectiveness of radiotherapy in some cases. We attempted to identify
      the differentially expressed genes in residual cervical cancer after radiotherapy
      that might be associated with poor prognosis and radioresistance.
      MATERIAL/METHODS: Differential genes expression was identified by an
      oligonucleotide microarray in cervical cancer tissues before radiation and after
      a 50-Gy dose of radiation. The microarray results were validated by quantitative
      real-time PCR. CXCL12 was validated by immunohistochemistry in paraffin-embedded
      cervical cancer tissues before radiotherapy. The relationship between the
      differentiated gene and prognosis was validated by survival analysis. RESULTS:
      Hierarchic cluster analysis identified 238 differentiated genes that exhibited
      >=3.0-fold change and p<0.05. We found 111 genes that were in persistent up
      regulation and 127 in persistent down-regulation after a 50-Gy dose of radiation
      when compared with the control group. These genes were involved in processes such
      as cell growth and death, cell-apoptosis, cell cycle regulation, cell signaling,
      DNA synthesis and repair, and cell adhesion. High differential expression of
      CXCL12, CD74, FGF7, COL14A1, PRC1, and RAD54L genes was validated by quantitative
      PCR before and after radiotherapy. Survival analysis results showed that the high
      expression of CXCL12 was closely related to poor prognosis. CONCLUSIONS: The
      higher expression of CXCL12 might be informative regarding poor prognosis in
      patients undergoing radical radiotherapy. The differentially expressed genes
      identified in our study might provide a new method for diagnosis and treatment of
      radioresistance in cervical cancer.

PMID- 25940977
TI  - Childhood hepatitis C virus infection: An Australian national surveillance study
      of incident cases over five years.
AB  - AIM: An estimated 1.1% of Australian adults are infected with hepatitis C virus
      (HCV). Many develop chronic liver disease, and some develop liver failure or
      hepatocellular carcinoma. HCV infection in Australian children is poorly defined.
      We aimed to determine the reported incidence, clinical and epidemiological
      features of newly diagnosed HCV infection in Australian children presenting to
      paediatricians. METHODS: We undertook prospective active national surveillance,
      using the Australian Paediatric Surveillance Unit, of incident HCV cases in
      children aged <15 years between 1(st) January 2003, and 31(st) December 2007.
      RESULTS: There were 45 confirmed cases of newly diagnosed HCV infection over five
      years (<1 per 100,000 children aged <15 years per year). Median age at diagnosis
      was 2.9 years. Positive maternal HCV serostatus was the most frequent reported
      risk factor for HCV infection in children (40/45). Three children (all aged >
      14), were exposed through their own IV drug use. No children were co-infected
      with HIV and only one child was co-infected with HBV. All children were
      asymptomatic at diagnosis, although many had minor elevations in liver
      transaminases. Many clinicians reported difficulties with follow-up. CONCLUSIONS:
      Childhood HCV infection is uncommon in Australia, although our data likely
      underestimate the incidence. Only a small number of children aged <18 months was
      identified, despite known perinatal exposure. Opportunistic investigation of
      children at risk for HCV, improved education regarding vertical transmission for
      health care providers, and increased coordination of childhood HCV services are
      required to improve recognition and management of children with HCV.

PMID- 25940979
TI  - Cyanidin-3-glucoside derived from black soybeans ameliorate type 2 diabetes
      through the induction of differentiation of preadipocytes into smaller and
      insulin-sensitive adipocytes.
AB  - Black soybean is a health food has been reported to have antidiabetes effect. The
      onset of diabetes is closely associated with adipocyte differentiation, and at
      present, the effect of black soybean on adipocyte differentiation is unknown.
      Here, we investigated the antidiabetes effect of black soybean, and its
      anthocyanin cyanidin-3-glucoside (Cy3G), on adipocyte differentiation. Orally
      administered black soybean seed coat extract (BSSCE) reduced the body and white
      adipose tissue (WAT) weight of db/db mice accompanied by a decrease in the size
      of adipocytes in WAT. Furthermore, 3T3-Ll cells treated with BSSCE and Cy3G were
      observed to differentiate into smaller adipocytes which correlated with increased
      PPARgamma and C/EBPalpha gene expressions, increased adiponectin secretion,
      decreased tumor necrosis factor-alpha secretion, activation of insulin signalling
      and increased glucose uptake. C2C12 myotubes cultured with conditioned medium,
      obtained from 3T3-L1 adipocyte cultures treated with Cy3G, also showed
      significantly increased expression of PGC-1alpha, SIRT1 and UCP-3 genes. Here we
      report that BSSCE, as well as its active compound Cy3G, has antidiabetes effects
      on db/db mice by promoting adipocyte differentiation. This notion is supported by
      BSSCE and Cy3G inducing the differentiation of 3T3-L1 preadipocytes into smaller,
      insulin-sensitive adipocytes, and it induced the activation of skeletal muscle
      metabolism. This is the first report on the modulation effect of Cy3G on
      adipocyte differentiation. 

PMID- 25940980
TI  - Analysis of lifespan-promoting effect of garlic extract by an integrated metabolo
      proteomics approach.
AB  - The beneficial effects of garlic (Allium sativum) consumption in treating human
      diseases have been reported worldwide over a long period of human history. The
      strong antioxidant effect of garlic extract (GE) has also recently been claimed
      to prevent cancer, thrombus formation, cardiovascular disease and some age
      related maladies. Using Caenorhabditis elegans as a model organism, aqueous GE
      was herein shown to increase the expression of longevity-related FOXO
      transcription factor daf-16 and extend lifespan by 20%. By employing microarray
      and proteomics analysis on C. elegans treated with aqueous GE, we have
      systematically mapped 229 genes and 46 proteins with differential expression
      profiles, which included many metabolic enzymes and yolky egg vitellogenins. To
      investigate the garlic components functionally involved in longevity, an
      integrated metabolo-proteomics approach was employed to identify metabolites and
      protein components associated with treatment of aqueous GE. Among potential
      lifespan-promoting substances, mannose-binding lectin and N-acetylcysteine were
      found to increase daf-16 expression. Our study points to the fact that the
      lifespan-promoting effect of aqueous GE may entail the DAF-16-mediated signaling
      pathway. The result also highlights the utility of metabolo-proteomics for
      unraveling the complexity and intricacy involved in the metabolism of natural
      products in vivo. 

PMID- 25940982
TI  - Cordycepin from Cordyceps militaris prevents hyperglycemia in alloxan-induced
      diabetic mice.
AB  - Cordyceps militaris has long been used in prescriptions of traditional Chinese
      medicine as a tonic for the treatment of metabolic syndrome. Cordycepin with
      proven immunomodulatory, antitumor, and hepatoprotective properties is the main
      active metabolite of C militaris. Diabetes mellitus is a group of metabolic
      diseases in which the body is unable to regulate blood sugar levels. Hence, we
      hypothesized that cordycepin can normalize blood sugar levels and improve the
      indicators of diabetes. The aim of this study was to investigate the possible
      effects of cordycepin from C militaris on diabetes in an alloxan-induced diabetic
      mouse model. Diabetic mice were intraperitoneally administered different doses of
      cordycepin (8, 24, and 72 mg/kg body weight) daily for 21 days. Acute toxicity
      test on normal mice was carried out by giving them maximum tolerance dose of
      cordycepin (3600 mg/kg) daily. A 47% reduction of the blood glucose level, 214%
      increase of hepatic glycogen content, and significant improvement of oral glucose
      tolerance were noticed after the effective dose of cordycepin was administered.
      Polyphagia and polydipsia, the typical symptoms of diabetes, were partly
      alleviated. Moreover, cordycepin offered protective effects against diabetes
      related kidney and spleen injury. Maximum tolerance dose test indicated that
      cordycepin at the large dose of 3600 mg/kg did not show significant effect on
      body weight and major organ in normal mice after intraperitoneal administration
      for 14 days. The results showed that cordycepin from C militaris that elicited
      hypoglycemic activity contributes to the regulation of glucose metabolism in
      liver in alloxan-induced diabetic mice. Therefore, a cordycepin treatment during
      diabetes can improve some of the metabolic syndrome symptoms by regulation of
      glucose absorption in vivo. Cordycepin may serve as a therapeutic agent in the
      treatment of diabetes and its related complications.

PMID- 25940983
TI  - The role of chairman and research director in influencing scholarly productivity
      and research funding in academic orthopaedic surgery.
AB  - The purpose of this study was to determine what orthopaedic surgery department
      leadership characteristics are most closely correlated with securing NIH funding
      and increasing scholarly productivity. Scopus database was used to identify
      number of publications/h-index for 4,328 faculty, department chairs (DC), and
      research directors (RD), listed on departmental websites from 138 academic
      orthopaedic departments in the United States. NIH funding data was obtained for
      the 2013 fiscal year. While all programs had a DC, only 46% had a RD. Of
      $54,925,833 in NIH funding allocated to orthopaedic surgery faculty in 2013, 3%
      of faculty and 31% of departments were funded. 16% of funded institutions had a
      funded DC whereas 65% had a funded RD. Department productivity and funding were
      highly correlated to leadership productivity and funding(p< 0.05). Mean funding
      was $1,700,000 for departments with a NIH-funded RD, $104,000 for departments
      with an unfunded RD, and $72,000 for departments with no RD. These findings
      suggest that orthopaedic department academic success is directly associated with
      scholarly productivity and funding of both DC and RD. The findings further
      highlight the correlation between a funded RD and a well-funded department. This
      does not hold for an unfunded RD.

PMID- 25940984
TI  - Gastrointestinal cancer: RAISE in second-line options for mCRC.

PMID- 25940985
TI  - Head and neck cancer: second-line afatinib shows promise.

PMID- 25940986
TI  - Genetics: clonal and subclonal events in cancer evolution--optimizing cancer
      therapy.

PMID- 25940987
TI  - Altered fibronectin expression and deposition by myeloproliferative neoplasm
      derived mesenchymal stromal cells.

PMID- 25940988
TI  - Analysis of Interactions between the Epidermal Growth Factor Receptor and Soluble
      Ligands on the Basis of Single-Molecule Diffusivity in the Membrane of Living
      Cells.
AB  - We present a single-molecule diffusional-mobility-shift assay (smDIMSA) for
      analyzing the interactions between membrane and water-soluble proteins in the
      crowded membrane of living cells. We found that ligand-receptor interactions
      decreased the diffusional mobility of ErbB receptors and beta-adrenergic
      receptors, as determined by single-particle tracking with super-resolution
      microscopy. The shift in diffusional mobility was sensitive to the size of the
      water-soluble binders that ranged from a few tens of kilodaltons to several
      hundred kilodaltons. This technique was used to quantitatively analyze the
      dissociation constant and the cooperativity of antibody interactions with the
      epidermal growth factor receptor and its mutants. smDIMSA enables the
      quantitative investigation of previously undetected ligand-receptor interactions
      in the intact membrane of living cells on the basis of the diffusivity of single
      molecule membrane proteins without ligand labeling. 

PMID- 25940989
TI  - Diagnostic performance of anti-cyclic citrullinated peptide and rheumatoid factor
      in patients with rheumatoid arthritis.
AB  - AIM: To compare the diagnostic performance of rheumatoid factor (RF) and anti
      cyclic citrullinated peptide antibody (anti-CCP) in the diagnosis of patients
      with rheumatoid arthritis (RA) in Taiwan. METHODS: Serum concentrations of RF and
      anti-CCP were measured in 246 cases, including 39 patients with RA and 207
      patients with other rheumatic diseases (non-RA). The age, sex, clinical
      presentation, RF, anti-CCP results and the final diagnoses were recorded and
      analyzed. The sensitivity, specificity, positive predictive value (PPV), negative
      predictive value (NPV), positive likelihood ratio (LR+) and negative likelihood
      ratio (LR-) were calculated. RESULTS: Among all 246 patients, 39 (15.9%) were
      diagnosed with RA and 207 (84.1%) were diagnosed with other rheumatic diseases
      (non-RA). In the diagnosis of RA, the sensitivity, specificity, PPV, NPV, LR+ and
      LR- of the RF test were 67%, 79%, 37%, 93%, 3.12, and 0.42, respectively. The
      corresponding data for the anti-CCP test were 79%, 98%, 86%, 96%, 32.91 and 0.21,
      respectively. The presence of either anti-CCP or RF increased the sensitivity to
      85%, and when they both were present, the specificity increased to 98%. Among the
      39 RA patients, 26 (66.7%) tested positive for RF, and 31 (79.5%) tested positive
      for anti-CCP. RF was positive in two of eight anti-CCP-negative patients with RA,
      and anti-CCP was positive in seven of 13 RF-negative patients with RA.
      CONCLUSIONS: The RF and anti-CCP tests are complementary, and the co-detection of
      these antibodies can increase the detection rate and provide important clinical
      value in the diagnosis of RA. Both anti-CCP and RF positivity are useful for the
      diagnosis of RA, and use of both tests together improves the diagnostic
      sensitivity.

PMID- 25940993
TI  - Sequence-based typing of HLA-A gene in 930 patients with nasopharyngeal carcinoma
      in Hunan province, southern China.
AB  - In this study, we typed 930 cases of nasopharyngeal carcinoma (NPC) and 1134
      normal controls recruited from Hunan province, southern China for human leukocyte
      antigen-A (HLA-A) locus by sequencing exons 2-4. Very significant associations
      between HLA-A*02:07, HLA-A*11:01 and NPC were established [25.7% vs 16.18%; odds
      ratio, OR (95% confidence interval, CI) = 1.79 (1.54-2.09), P < 0.0001 and 21.1%
      vs 30.42%, OR (95% CI) = 0.61 (0.53-0.70), P<0.0001, respectively]. Further
      analysis of the molecular basis underlying these associations suggests that
      cysteine (C) at codon 99 of alpha2-helix of HLA-A protein is probably deleterious
      and confers risk to NPC. Convincing evidence was uncovered for negative
      association of a rare allele in southern Chinese populations, HLA-A*31:01, with
      NPC [0.22% vs 2.12%, OR (95% CI) = 0.1 (0.04-0.28), P < 0.0001]. rs1059449-A,
      which encodes arginine (R) at codon 56 of alpha1-helix of HLA-A protein, was
      postulated to be crucial for such a pattern of negative association with NPC. A
      subset of NPC cases (N = 632) and normal controls (N=712) were tested for anti
      virus capsid antigen (anti-VCA) immunoglobulin A (IgA), very significant
      difference in seropositivity for anti-VCA IgA was observed between the two groups
      [67.56% vs 6.46%, OR (95% CI) = 30.16 (21.42-42.46), P < 0.0001]. However,
      seropositivity for anti-VCA IgA did not correlate with HLA-A allelic typing in
      both groups. 

PMID- 25940994
TI  - Force-Driven Single-Atom Manipulation on a Low-Reactive Si Surface for Tip
      Sharpening.
AB  - A single atomic manipulation on the delta-doped B:Si(111)-(?3x?3)R30 degrees 
      surface using a low temperature dynamic atomic force microscopy based on the
      Kolibri sensor is investigated. Through a controlled vertical displacement of the
      probe, a single Si adatom in order to open a vacancy is removed. It is shown that
      this process is completely reversible, by accurately placing a Si atom back into
      the vacancy site. In addition, density functional theory simulations are carried
      out to understand the underlying mechanism of the atomic manipulation in detail.
      This process also rearranges the atoms at the tip apex, which can be effectively
      sharpened in this way. Such sharper tips allow for a deeper look into the Si
      adatom vacancy site. Namely, high-resolution images of the vacancy showing
      subsurface Si dangling bond triplets, which surround the substitutional B dopant
      atom in the first bilayer, are achieved.

PMID- 25940995
TI  - Cell cycle and apoptosis regulatory proteins, proliferative markers, cell
      signaling molecules, CD209, and decorin immunoreactivity in low-grade
      myxofibrosarcoma and myxoma.
AB  - The histologic differential diagnosis between intramuscular myxoma and low-grade
      myxofibrosarcoma can be quite difficult in some cases. To identify a diagnostic
      immunohistochemical marker, we compared the staining profiles of 19 different
      antigens, including cell cycle proteins, apoptosis proteins, and proliferative
      markers, and selected other signaling and structural proteins in these two
      tumors. Ten cases each of intramuscular myxoma and low-grade myxofibrosarcoma
      were stained with antibodies directed against apoptosis regulatory proteins
      (Bcl2, activated caspase-3, phospho-H2A.X, and cleaved PARP), cell cycle
      regulatory proteins (Rb1, Cyclin-A, CDKN1B, and Cdt1), proliferative markers
      (KI67, MCM2, phospho-histone H3, and geminin), cell signalling molecules (c-Myc,
      EGF, EGFR, PLA2G4A, and HSP90), a dendritic cell marker (CD209), and the
      extracellular matrix proteoglycan decorin. Staining patterns of myxoma and
      myxofibrosarcoma were compared using Fisher's exact test and the Mann-Whitney
      test. For each potential diagnostic marker studied, the proportions of cases
      scored as positive on both dichotomous or ordinal scales were not significantly
      different between myxoma and myxofibrosarcoma. Myxoma and myxofibrosarcoma share
      a common immunophenotype for each of the markers studied. Distinction between
      these tumors is still predominantly based on morphologic criteria.

PMID- 25940997
TI  - Prevalence and Outcomes of Patients Meeting Palliative Care Consultation Triggers
      in Neurological Intensive Care Units.
AB  - BACKGROUND: Palliative care needs among patients in the neurological intensive
      care unit (neuroICU) are poorly characterized. Our aim was to explore the
      prevalence and type of potential palliative care consultation triggers in
      neuroICUs. METHODS: We conducted a retrospective cohort study of neuroICU
      admissions in Project IMPACT from 2001 to 2008. We assessed the prevalence of
      neuroICU admissions meeting one or more of five validated palliative care
      consultation triggers and compared the percentage of admissions meeting these
      triggers in other ICUs from the same hospitals. RESULTS: Among 1268 admissions to
      2 neuroICUs, 200 (15.8 %) met one or more triggers for palliative care
      consultation. Among 13,694 admissions to non-neuroICUs in the same hospitals,
      1909 (13.9 %) met one or more palliative care triggers (p = 0.44). The most
      common trigger in the neuroICU was intracerebral hemorrhage with mechanical
      ventilation (n = 92; 7.3 %). The most common trigger in non-neuroICUs was ICU
      admission following >=10-day hospital stay (n = 805; 5.9 %). Although ICU
      mortality was not significantly higher in neuroICU vs. non-neuroICU patients
      meeting triggers (23.4 vs 19.9 %, p = 0.46), neuroICU patients were significantly
      more likely to have withdrawal of life-sustaining therapies (19.4 vs 8.0 %, p <
      0.001). CONCLUSIONS: Among neuroICU patients, 15.8 % met triggers for palliative
      care consultation. Although prevalence of admissions meeting any trigger was
      similar amongst all ICUs, neuroICU admissions met different types of triggers and
      were more likely to have withdrawal of life-sustaining therapy. These data
      suggest that palliative care needs are common among neuroICU patients and
      discussions with patients and families regarding limitation of life-sustaining
      therapy may differ in this setting.

PMID- 25940996
TI  - Impact of adjuvant taxane-based chemotherapy on development of breast cancer
      related lymphedema: results from a large prospective cohort.
AB  - Taxane-based chemotherapy for the treatment of breast cancer is associated with
      fluid retention in the extremities; however, its association with development of
      breast cancer-related lymphedema is unclear. We sought to determine if adjuvant
      taxane-based chemotherapy increased risk of lymphedema or mild swelling of the
      upper extremity. 1121 patients with unilateral breast cancer were prospectively
      screened for lymphedema with perometer measurements. Lymphedema was defined as a
      relative volume change (RVC) of >=10 % from preoperative baseline. Mild swelling
      was defined as RVC 5- <10 %. Clinicopathologic characteristics were obtained via
      medical record review. Kaplan-Meier and Cox proportional hazard analyses were
      performed to determine lymphedema rates and risk factors. 29 % (324/1121) of
      patients were treated with adjuvant taxane-based chemotherapy. The 2-year
      cumulative incidence of lymphedema in the overall cohort was 5.27 %. By
      multivariate analysis, axillary lymph node dissection (ALND) (p < 0.0001), higher
      body mass index (p = 0.0007), and older age at surgery (p = 0.04) were
      significantly associated with increased risk of lymphedema; however, taxane
      chemotherapy was not significant when compared to no chemotherapy and non-taxane
      chemotherapy (HR 1.14, p = 0.62; HR 1.56, p = 0.40, respectively). Chemotherapy
      with docetaxel was significantly associated with mild swelling on multivariate
      analysis in comparison to both no chemotherapy and non-taxane chemotherapy groups
      (HR 1.63, p = 0.0098; HR 2.15, p = 0.02, respectively). Patients who receive
      taxane-based chemotherapy are not at an increased risk of lymphedema compared to
      patients receiving no chemotherapy or non-taxane adjuvant chemotherapy. Those
      treated with docetaxel may experience mild swelling, but this does not translate
      into subsequent lymphedema.

PMID- 25940998
TI  - Continuous non-invasive monitoring to detect covert autonomic dysfunction in
      Parkinson's disease.
AB  - BACKGROUND: Lightheadedness on standing is a disabling symptom in Parkinson's
      disease associated with orthostatic hypotension and is thought to represent
      cardiovascular autonomic dysfunction. Traditional orthostatic blood pressures are
      normal in some patients with lightheadedness and other measures of cardiovascular
      dysautonomia can be insensitive. In this study, we used continuous non-invasive
      arterial pressure monitoring to measure beat-to-beat changes in blood pressure
      and heart rate on standing and during Valsalva as a potential marker of autonomic
      dysfunction. METHODS: Subjects had a diagnosis of Parkinson's disease with or
      without documented orthostatic hypotension. Each participant underwent
      traditional measurement of orthostatic blood pressure and heart rate as well as
      measurement of beat-to-beat blood pressure and heart rate using continuous non
      invasive arterial pressure monitoring during Valsalva maneuver and in response to
      standing. Orthostatic change in blood pressure and heart rate, and frequencies of
      normal and abnormal blood pressure responses to Valsalva maneuver were analyzed.
      RESULTS: In subjects without documented orthostatic hypotension, there was a
      higher proportion of abnormal blood pressure responses to Valsalva in subjects
      with symptoms of lightheadedness or dizziness upon standing compared to those
      without symptoms (p = 0.03). Additionally, the proportion of abnormal blood
      pressure responses during Valsalva observed in symptomatic subjects without
      orthostatic hypotension was indistinguishable from those with documented
      orthostatic hypotension (p = 0.7). CONCLUSIONS: Our findings suggest that
      continuous non-invasive arterial pressure monitoring may be more sensitive than
      traditional measurement of orthostatic blood pressure to detect subtle cardiac
      dysautonomia in Parkinson's disease and helpful in the diagnosis of unexplained
      lightheadedness.

PMID- 25940999
TI  - Does the Pisa syndrome affect postural control, balance, and gait in patients
      with Parkinson's disease? An observational cross-sectional study.
AB  - INTRODUCTION: An altered sense of verticality, associated with impaired
      proprioception and somatosensory integration deficits, has been reported in
      patients with Parkinson's disease (PD) but it has not been characterized in
      patients with Pisa syndrome (PS). Therefore, we investigated postural control,
      balance, and gait disturbances in patients with PD and PS, patients with PD but
      without PS, and aged-matched normal controls. METHODS: This observational cross
      sectional study involved patients with PD and PS (n = 10, Hoehn & Yahr score <4),
      patients with PD but without PS (n = 10), and age-matched healthy controls (n =
      10). The primary outcome measure was the velocity of CoP displacement
      (VEL_MED_AP/ML) assessed by static stabilometry in eyes open (EO) and eyes closed
      (EC) conditions. The secondary outcomes were other stabilometric parameters, the
      Sensory Organization Balance Test (SOT), and gait analysis (GA). RESULTS: There
      were no significant differences in demographic and clinical data and Berg Balance
      Scale scores between the groups. There was a significant main effect in the
      VEL_MED_AP/ML between the groups and eye conditions (p = .016). A significant
      main effect was found in the EO (p = .01) and EC (p = .04) conditions. Post-hoc
      comparisons showed a significant increase in VEL_CoP in both the EO and EC
      conditions only in the patients with PD and PS. No significant main effects on
      SOT and GA were found. CONCLUSION: Patients with PD and PS had more difficulty
      achieving good postural alignment with gravity and greater velocity of body sway
      than the other groups. Rehabilitation programs for patients with PD and PS should
      include spine alignment and dynamic postural training.

PMID- 25941000
TI  - Risk factors for Dandy-Walker malformation: a population-based assessment.
AB  - Dandy-Walker malformation (DWM) is the most common congenital malformation of the
      cerebellum, but its causes are largely unknown. An increasing number of genes
      associated with congenital cerebellar malformations have been identified;
      however, few studies have examined the potential role of non-genetic, potentially
      modifiable risk factors. From the National Birth Defects Prevention Study, we
      examined maternal, paternal, and infant characteristics and maternal conditions
      and periconceptional exposures (from 1 month before to 3 months after conception)
      among infants with DWM (n = 160) and unaffected controls (n = 10,200), delivered
      between 1997 and 2009. Odds ratios, crude (cOR) and adjusted (aOR) were computed
      using logistic regression. Maternal factors associated with DWM included non
      Hispanic black race/ethnicity (aOR = 2.0, 95%CI: 1.3-3.2). Among maternal
      conditions, a history of infertility increased the risk for DWM (all: aOR = 2.4,
      95%CI: 1.3-4.6; multiple: aOR = 3.9, 95%CI: 1.7-8.9). The lack of association
      with many maternal exposures supports the hypothesis of a major contribution of
      genetic factors to the risk for DWM; however, the observed associations with
      maternal non-Hispanic black race/ethnicity and maternal history of infertility
      indicate that further research into factors underlying these characteristics may
      uncover potentially modifiable risk factors, acting alone or as a component of
      gene-environment interactions.

PMID- 25941001
TI  - Carbon Dioxide and Acetate-Free Biofiltration: A Relationship to be Investigated.
AB  - As the name reveals, acetate-free biofiltration (AFB) is featured by lack of
      acetate and this would seem to allow better hemodynamic stability. However, AFB
      also has a unique characteristic of carbon dioxide (CO2 )-free dialysate, whereas
      all other modern dialysis techniques imply an overload of CO2 from dialysate to
      the patient. This notwithstanding the role of CO2 in tolerance to dialysis
      treatment, both AFB and all other dialysis techniques seem not investigated in
      due depth. Specifically, the amount of CO2 coming back to the patient's
      bloodstream during AFB and bicarbonate dialysis (BD) is unknown. We measured
      partial pressure of CO2 (pCO2 ) in blood samples withdrawn from the venous line
      of the extracorporeal circuit during BD and subsequently during AFB in 22 stable
      chronic hemodialysis outpatients. The amount of CO2 coming back to the patient's
      bloodstream is higher in BD (59.1 +/- 4.0 mmol/L) than in AFB (42.8 +/- 4.5
      mmol/L, P < 0.0001). Such difference exceeds 30%. Moreover, shifting from BD to
      AFB shows, notably for each patient, the reduction of pCO2 toward physiological
      values. BD implies CO2 overload from dialysate, whereas AFB does not. Further
      studies are required to evaluate if AFB would be the most appropriate dialysis
      technique in patients affected by chronic, but especially acute, lung diseases. 

PMID- 25941002
TI  - Glutaminase activity determines cytotoxicity of L-asparaginases on most leukemia
      cell lines.
AB  - L-Asparaginase (ASNase) is a front-line chemotherapy for acute lymphoblastic
      leukemia (ALL), which acts by deaminating asparagine and glutamine. To evaluate
      the importance of glutaminase activity, we exploited a recently developed mutant
      of Helicobacter pylori ASNase (dm HpA), with amino acid substitutions
      M121C/T169M. The mutant form has the same asparaginase activity as wild-type but
      lacks glutaminase activity. Wild-type and dm HpA were compared with the
      clinically used ASNases from Escherichia coli (l-ASP) and Erwinia chrysanthemi
      (ERWase). Asparaginase activity was similar for all isoforms, while glutaminase
      activity followed the rank order: ERWase>l-ASP>wild-type HpA>dm HpA. Cytotoxic
      efficacy of ASNases was tested on 11 human leukemia cell lines and two patient
      derived ALL samples. Two cell lines which we had previously shown to be
      asparagine-dependent were equally sensitive to the asparaginase isoforms. The
      other nine lines and the two patient-derived samples were more sensitive to
      isoforms with higher glutaminase activities. ERWase was overall the most
      effective ASNase on all cell lines tested whereas dm HpA, having the lowest
      glutaminase activity, was the least effective. These data demonstrate that
      asparaginase activity alone may not be sufficient for ASNase cytotoxicity, and
      that glutaminase activity may be required for full anti-leukemic efficacy.

PMID- 25941004
TI  - Generation of a pair of independently binding DNA aptamers in a single round of
      selection using proximity ligation.
AB  - The ability to rapidly generate a pair of aptamers that bind independently to a
      protein target would greatly extend their use as reagents for two site
      ('sandwich') assays. We describe here a method to achieve this through proximity
      ligation. Using lysozyme as a target we demonstrate that under optimal conditions
      such a pair of aptamers, with nanomolar affinities, can be generated in a single
      round. 

PMID- 25941006
TI  - A general route to monoorganopnicogen(III) (M = Sb, Bi) compounds with a pincer
      (N,C,N) group and oxo ligands.
AB  - The reaction of RMCl2 [R = 2,6-[MeN(CH2CH2)2NCH2]2C6H3; M = Sb (1), Bi (2)] with
      KOH affords the isolation of the oxides cyclo-R2M2O2 [M = Sb (3), Bi (4)].
      Treatment of 3 with trifluoroacetic acid produced an ionic species (5) with a
      dinuclear cation that contains organic ligands protonated partially at one of the
      pendant arms. The cyclic oxides 3 and 4 are able to trap gaseous CO2 to give
      "RMCO3" [M = Sb (6), Bi (7)], the degree of these organometallic carbonates'
      oligomerization being under investigation. The reactivity of the dinuclear oxide
      3 was also investigated towards oxalic acid or dopamine hydrochloride and pure
      mononuclear compounds could be isolated, i.e. RSb[O(O)CC(O)O] (8) and RSb[O2-1,2
      C6H3-3-(CH2)2NH3]Cl (9). The reaction of the dichlorides 1 and 2 with ethylene
      glycol, pinacol or catechol, in the presence of KOH, led to 2-organo-1,3,2
      dioxastibolanes or -bismolanes RM(OCH2)2 [M = Sb (10), Bi (11)], RM(OCMe2)2 [M =
      Sb (12), Bi (13)] and 2-organo-1,3,2-dioxastibole or -bismole RM(O2-1,2-C6H4) [M
      = Sb (14), Bi (15)], respectively. The compounds were investigated by NMR
      spectroscopy, including variable temperature experiments, providing evidence for
      the presence of the intramolecular N->M interactions in solution. Single crystal
      X-ray diffraction studies were performed for most compounds and revealed an
      organic group R acting as a pincer ligand resulting in a distorted square
      pyramidal (N,C,N)MO2 core with cis intramolecular N->M interactions placed trans
      to M-O bonds. This is in contrast to the N->M interactions trans to each other as
      found in the RMCl2 used as starting materials. The crystals of the oxides 3 and
      4.4H2O contain different geometric isomers with anti and syn orientation of the M
      C bonds, respectively, with respect to the planar M2O2 ring. In the
      supramolecular polymeric architecture established in the crystal of 4.4H2O an
      important finding is the experimental observation of water hexamer units with a
      [tetramer + 2] structure (water molecules connected to opposite corners of a
      square water tetramer) fixed between 1D-chains of the type (syn-R2Bi2O2.H2O)n
      through additional hydrogen bonds to oxygen atoms of the dinuclear
      organobismuth(III) moieties. Theoretical calculations were carried out on 2-6 and
      8-15 in order to gain insight into the stabilization energy produced by
      intramolecular coordination of the pendant arms, association degrees and
      formation energies of the organopnicogen compounds with chelating ligands.

PMID- 25941003
TI  - Niche signaling promotes stem cell survival in the Drosophila testis via the JAK
      STAT target DIAP1.
AB  - Tissue-specific stem cells are thought to resist environmental insults better
      than their differentiating progeny, but this resistance varies from one tissue to
      another, and the underlying mechanisms are not well-understood. Here, we use the
      Drosophila testis as a model system to study the regulation of cell death within
      an intact niche. This niche contains sperm-producing germline stem cells (GSCs)
      and accompanying somatic cyst stem cells (or CySCs). Although many signals are
      known to promote stem cell self-renewal in this tissue, including the highly
      conserved JAK-STAT pathway, the response of these stem cells to potential death
      inducing signals, and factors promoting stem cell survival, have not been
      characterized. Here we find that both GSCs and CySCs resist cell death better
      than their differentiating progeny, under normal laboratory conditions and in
      response to potential death-inducing stimuli such as irradiation or starvation.
      To ask what might be promoting stem cell survival, we characterized the role of
      the anti-apoptotic gene Drosophila inhibitor of apoptosis 1 (diap1) in testis
      stem cells. DIAP1 protein is enriched in the GSCs and CySCs and is a JAK-STAT
      target. diap1 is necessary for survival of both GSCs and CySCs, and ectopic up
      regulation of DIAP1 in somatic cyst cells is sufficient to non-autonomously
      rescue stress-induced cell death in adjacent differentiating germ cells
      (spermatogonia). Altogether, our results show that niche signals can promote stem
      cell survival by up-regulation of highly conserved anti-apoptotic proteins, and
      suggest that this strategy may underlie the ability of stem cells to resist death
      more generally. 

PMID- 25941005
TI  - Return to Work in Out-of-Hospital Cardiac Arrest Survivors: A Nationwide Register
      Based Follow-Up Study.
AB  - BACKGROUND: Data on long-term function of out-of-hospital cardiac arrest
      survivors are sparse. We examined return to work as a proxy of preserved function
      without major neurologic deficits in survivors. METHODS AND RESULTS: In Denmark,
      out-of-hospital cardiac arrests have been systematically reported to the Danish
      Cardiac Arrest Register since 2001. During 2001-2011, we identified 4354 patients
      employed before arrest among 12 332 working-age patients (18-65 years), of whom
      796 survived to day 30. Among 796 survivors (median age, 53 years [quartile 1-3,
      46-59 years]; 81.5% men), 610 (76.6%) returned to work in a median time of 4
      months [quartile 1-3, 1-19 months], with a median time of 3 years spent back at
      work. A total of 74.6% (N=455) remained employed without using sick leave during
      the first 6 months after returning to work. This latter proportion of survivors
      returning to work increased over time (66.1% in 2001-2005 versus 78.1% in 2006
      2011; P=0.002). In multivariable Cox regression analysis, factors associated with
      return to work with >=6 months of sustainable employment were as follows: (1)
      arrest during 2006-2011 versus 2001-2005, hazard ratio (HR), 1.38 (95% CI, 1.05
      1.82); (2) male sex, HR, 1.48 (95% CI, 1.06-2.07); (3) age of 18 to 49 versus 50
      to 65 years, HR, 1.32 (95% CI, 1.02-1.68); (4) bystander-witnessed arrest, HR,
      1.79 (95% CI, 1.17-2.76); and (5) bystander cardiopulmonary resuscitation, HR,
      1.38 (95% CI, 1.02-1.87). CONCLUSIONS: Of 30-day survivors employed before
      arrest, 76.6% returned to work. The percentage of survivors returning to work
      increased significantly, along with improved survival during 2001-2011,
      suggesting an increase in the proportion of survivors with preserved function
      over time.

PMID- 25941007
TI  - Bed Sharing, SIDS Research, and the Concept of Confounding: A Review for Public
      Health Nurses.
AB  - Confounding is an important concept for public health nurses (PHNs) to understand
      when considering the results of epidemiological research. The term confounding is
      derived from Latin, confundere, which means to "mix-up" or "mix together".
      Epidemiologists attempt to derive a cause and effect relationship between two
      variables traditionally known as the exposure and disease (e.g., smoking and lung
      cancer). Confounding occurs when a third factor, known as a confounder, leads to
      an over- or underestimate of the magnitude of the association between the
      exposure and disease. An understanding of confounding will facilitate critical
      appraisal of epidemiological research findings. This knowledge will enable PHNs
      to strengthen their evidence-based practice and better prepare them for policy
      development and implementation. In recent years, researchers and clinicians have
      examined the relationship between bed sharing and sudden infant death syndrome
      (SIDS). The discussion regarding the risk of bed sharing and SIDS provides ample
      opportunity to discuss the various aspects of confounding. The purpose of this
      article is to use the bed sharing and SIDS literature to assist PHNs to
      understand confounding and to apply this knowledge when appraising
      epidemiological research. In addition, strategies that are used to control
      confounding are discussed. 

PMID- 25941008
TI  - Recognition of human milk oligosaccharides by bacterial exotoxins.
AB  - The affinities of the most abundant oligosaccharides found in human milk for four
      bacterial exotoxins (from Vibrio cholerae and pathogenic Escherichia coli) were
      quantified for the first time. Association constants (Ka) for a library of 20
      human milk oligosaccharides (HMOs) binding to Shiga toxin type 2 holotoxin (Stx2)
      and the B subunit homopentamers of cholera toxin, heat-labile toxin and Shiga
      toxin type 1 (CTB5, HLTB5 and Stx1B5) were measured at 25 degrees C and pH 7
      using the direct electrospray ionization mass spectrometry assay. Notably, all
      four bacterial toxins bind to a majority of the HMOs tested and five of the HMOs
      (2'-fucosyllactose, lacto-N-tetraose, lacto-N-fucopentaose I, lacto-N
      fucopentaose II and lacto-N-fucopentaose III) are ligands for all four toxins.
      These five HMOs are also reported to bind to other bacterial toxins (e.g. toxin A
      and toxin B of Clostridium difficile). In all cases, the HMO affinities (apparent
      Ka) are relatively modest (<=15,000 M(-1)). However, at the high concentrations
      of HMOs typically ingested by infants, a significant fraction of these toxins, if
      present, is expected to be bound to HMOs. Binding measurements carried out with
      2'-fucosyllactose or lacto-N-fucopentaose I, together with a high-affinity ligand
      based on the native carbohydrate receptor, revealed that all four toxins possess
      HMO-binding sites that are distinct from those of the native receptors, although
      evidence of competitive binding was found for lacto-N-fucopentaose I with Stx2
      and 2'-fucosyllactose and lacto-N-fucopentaose I with HLTB5. Taken together, the
      results of this study suggest that, while HMOs are expected to bind extensively
      to these bacterial toxins, it is unlikely that HMO binding will effectively
      inhibit their interactions with their cellular receptors.

PMID- 25941009
TI  - Rational Modification of the Biological Profile of GPCR Ligands through
      Combination with Other Biologically Active Moieties.
AB  - In recent years, G protein-coupled receptor (GPCR) ligands have not only been
      modified by conducting structure-activity relationship studies of leads and known
      ligands, but several new approaches have emerged in which GPCR ligands were
      connected or merged with other biologically active molecules. Identical or
      related ligands were combined to bivalent ones. Orthosteric ligands were combined
      with allosteric ligands, sometimes leading to dualsteric ones, and also chemical
      structures were merged to dual-acting or multifunctional compounds. In this
      article, we want to present some representative examples for these approaches at
      different GPCRs, showing the versatility of this approach, with a focus on our
      own work and references to related articles and reviews. 

PMID- 25941010
TI  - Radiographic comparison of cross-sectional lumbar pedicle fill when placing
      screws with navigation versus free-hand technique.
AB  - BACKGROUND: Pedicle screws are often used for spinal fixation. Increasing the
      percentage of pedicle that is filled with the screw presumably yields greater
      fixation. It has not been shown whether spinal navigation helps surgeons more
      completely fill their instrumented pedicles. METHODS: Fifty consecutive patients
      from each arm (navigated and free-hand) were retrospectively reviewed. The cross
      sectional area of each instrumented lumbar pedicle and screw were measured using
      an automatic area calculation tool. The coronal images and measurements were
      blinded to the surgeons. RESULTS: The instrumented pedicles in the navigated
      patients were significantly more filled by screws than the pedicles in the non
      navigated patients (P < 0.001). CONCLUSION: Obtaining a higher cross-sectional
      percentage fill of the pedicle with a screw is expected to provide greater spinal
      fixation in instrumented fusion surgery. This study shows that utilizing spinal
      navigation helps to more completely fill the pedicles that are being
      instrumented. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 25941011
TI  - Ellagic acid: Pharmacological activities and molecular mechanisms involved in
      liver protection.
AB  - Traditional drugs or therapies rarely have effects on regression of chronic liver
      diseases, which result in many cases from sustained oxidative stress. In recent
      years, ellagic acid (EA) has gained attention due to its multiple biological
      activities and several molecular targets. This is the first review focused on the
      pharmacological properties and on the molecular mechanisms activated by EA in
      terms of liver protection. EA possesses antioxidant, antihepatotoxic,
      antisteatosic, anticholestatic, antifibrogenic, antihepatocarcinogenic and
      antiviral properties that improves the hepatic architectural and functions
      against toxic and pathological conditions. The molecular mechanisms that EA
      activates include the scavenging of free radicals, regulation of phase I and II
      enzymes, modulation of proinflammatory and profibrotic cytokines synthesis, the
      regulation of biochemical pathways involved in the synthesis and degradation of
      lipids as well as the maintenance of essential trace elements levels. EA also
      inhibits hepatic stellate cells and mast cells activation, the proliferation of
      transformed cells, as well as viral replication by increasing antioxidant
      response, induction of apoptosis, downregulation of genes involved in cell cycle
      and angiogenesis, and stimulation of cellular immune response. Despite the
      enormous therapeutic potential of EA as an innovative pharmacological strategy,
      the number of phase I and II trials in patients is scarce, precluding its
      clinical application. In these sense, the use of new delivery systems that
      enhances EA bioavailability would improve the results already obtained. Also it
      remains to be determined if treatment with urolithins instead of EA would
      represent a better strategy in hepatic disease treatment. 

PMID- 25941012
TI  - Self-reported occupational exposure to chemical and physical factors and risk of
      skin problems: a 3-year follow-up study of the general working population of
      Norway.
AB  - Prospective studies on occupational dermatoses in the general working population
      are sparse. This study investigated prospectively the impact of self-reported
      occupational exposure to chemicals and physical factors on the risk of skin
      problems. The cohort comprised respondents drawn randomly from the general
      population in Norway, who were registered employed in 2006 and 2009 (n = 6,745).
      Indoor dry air (odds ratio (OR) 1.3; 95% confidence interval (95% CI) 1.1-1.6)
      was a significant baseline predictor of skin problems at follow-up, whereas
      exposure to cleaning products (OR 1.7; 95% CI 1.2-2.5), water (OR 1.4; 95% CI 1.1
      1.9) and indoor dry air (OR 1.6; 95% CI 1.1-2.1) at both measurement time-points
      was significantly associated with skin problems. The population risk attributable
      to these factors was 16%. This study quantified the contribution of occupational
      exposure factors to skin problems in the general working population of Norway. 

PMID- 25941013
TI  - Frequency analysis of a task-evoked pupillary response: Luminance-independent
      measure of mental effort.
AB  - Pupil diameter is a widely-studied cognitive load measure, which, despite its
      convenience for non-intrusive operator state monitoring in complex environments,
      is still not available for in situ measurements because of numerous
      methodological limitations. The most important of these limitations is the
      influence of pupillary light reflex. Hence, there is the need of providing a
      pupil-based cognitive load measure that is independent of light conditions. In
      this paper, we present a promising technique of pupillary signal analysis
      resulting in luminance-independent measure of mental effort that could be used in
      real-time without a priori on luminous conditions. Twenty-two participants
      performed a short-term memory task under different screen luminance conditions.
      Our results showed that the amplitude of pupillary dilation due to load on memory
      was luminance-dependent with higher amplitude corresponding to lower-luminance
      condition. Furthermore, our experimentation showed that load on memory and
      luminance factors express themselves differently according to frequency.
      Therefore, as our statistical analysis revealed, the ratio between low (0-1.6 Hz)
      and high frequency (1.6-4 Hz) bands (LF/HF ratio) of power spectral densities of
      pupillary signal is sensitive to the cognitive load but not to luminance. Our
      results are promising for the measurement of load on memory in ecological
      settings.

PMID- 25941015
TI  - Absolute asymmetric synthesis of a tetrahedral silver complex.
AB  - Even though the isolation of tetrahedral stereoisomers usually presents a
      synthetic challenge, a highly enantioenriched tetrahedral silver complex could be
      easily accessed by either crystallization or Viedma ripening. The overall
      preparation may be regarded as an example of absolute asymmetric synthesis.
      Experimental results indicate that both crystallization and Viedma ripening
      follow a similar cluster-controlled mechanism. 

PMID- 25941014
TI  - When treating the pain is not enough: a multidisciplinary approach for chronic
      pelvic pain.
AB  - Chronic pelvic pain (CPP) is related to psychological distress and interference
      in daily activities; however, CPP is not as extensively researched as other forms
      of chronic pain. Therefore, the purpose of this study was to investigate the
      relationships among pain, psychological distress, and functional impairment in
      patients with CPP. There were chart reviews conducted of 107 female patients who
      completed a psychiatric evaluation at a specialty, CPP clinic as a part of a
      multidisciplinary evaluation. Results suggest that psychological distress and
      impairment in daily activities are common in CPP patients. Most areas of
      functional impairment were not associated with pain variables. Rather, several
      forms of functional impairment were related to higher levels of depression and
      anxiety. Results from this study suggest the possibility that psychiatric
      symptoms are contributing to functional impairment in this population. These
      findings highlight the importance of a multidisciplinary approach in the
      evaluation and treatment of CPP patients to help decrease functional impairment
      in these patients. 

PMID- 25941017
TI  - Long-term healthy obesity may be exceptional worldwide.

PMID- 25941016
TI  - AVP-825 breath-powered intranasal delivery system containing 22 mg sumatriptan
      powder vs 100 mg oral sumatriptan in the acute treatment of migraines (The
      COMPASS study): a comparative randomized clinical trial across multiple attacks.
AB  - OBJECTIVE: The objective of this study was to compare the efficacy, tolerability,
      and safety of AVP-825, an investigational bi-directional breath-powered
      intranasal delivery system containing low-dose (22 mg) sumatriptan powder, vs 100
      mg oral sumatriptan for acute treatment of migraine in a double-dummy, randomized
      comparative efficacy clinical trial allowing treatment across multiple migraine
      attacks. BACKGROUND: In phases 2 and 3, randomized, placebo-controlled trials,
      AVP-825 provided early and sustained relief of moderate or severe migraine
      headache in adults, with a low incidence of triptan-related adverse effects.
      METHODS: This was a randomized, active-comparator, double-dummy, cross-over,
      multi-attack study (COMPASS; NCT01667679) with two <=12-week double-blind
      periods. Subjects experiencing 2-8 migraines/month in the past year were
      randomized 1:1 using computer-generated sequences to AVP-825 plus oral placebo
      tablet or an identical placebo delivery system plus 100 mg oral sumatriptan
      tablet for the first period; patients switched treatment for the second period in
      this controlled comparative design. Subjects treated <=5 qualifying migraines per
      period within 1 hour of onset, even if pain was mild. The primary end-point was
      the mean value of the summed pain intensity differences through 30 minutes post
      dose (SPID-30) using Headache Severity scores. Secondary outcomes included pain
      relief, pain freedom, pain reduction, consistency of response across multiple
      migraines, migraine-associated symptoms, and atypical sensations. Safety was also
      assessed. RESULTS: A total of 275 adults were randomized, 174 (63.3%) completed
      the study (ie, completed the second treatment period), and 185 (67.3%) treated at
      least one migraine in both periods (1531 migraines assessed). There was
      significantly greater reduction in migraine pain intensity with AVP-825 vs oral
      sumatriptan in the first 30 minutes post-dose (least squares mean SPID-30 = 10.80
      vs 7.41, adjusted mean difference 3.39 [95% confidence interval 1.76, 5.01]; P <
      .001). At each time point measured between 15 and 90 minutes, significantly
      greater rates of pain relief and pain freedom occurred with AVP-825 treatment
      compared with oral sumatriptan. At 2 hours, rates of pain relief and pain freedom
      became comparable; rates of sustained pain relief and sustained pain freedom from
      2 to 48 hours remained comparable. Nasal discomfort and abnormal taste were more
      common with AVP-825 vs oral sumatriptan (16% vs 1% and 26% vs 4%, respectively),
      but ~90% were mild, leading to only one discontinuation. Atypical sensation rates
      were significantly lower with AVP-825 than with conventional higher dose 100 mg
      oral sumatriptan. CONCLUSIONS: AVP-825 (containing 22 mg sumatriptan nasal
      powder) provided statistically significantly greater reduction of migraine pain
      intensity over the first 30 minutes following treatment, and greater rates of
      pain relief and pain freedom within 15 minutes, compared with 100 mg oral
      sumatriptan. Sustained pain relief and pain freedom through 24 and 48 hours was
      achieved in a similar percentage of attacks for both treatments, despite
      substantially lower total systemic drug exposure with AVP-825. Treatment was well
      tolerated, with statistically significantly fewer atypical sensations with AVP
      825.

PMID- 25941018
TI  - First Molecular Characterization of Cryptosporidium spp. Infecting Buffalo Calves
      in Brazil.
AB  - With the aim of determining the occurrence of Cryptosporidium spp., 222 fecal
      samples were collected from Murrah buffalo calves aged up to 6 mo. Fecal DNA was
      genotyped with a nested polymerase chain reaction targeting the 18S rRNA gene and
      sequencing of the amplified fragment. Nested 18S PCR was positive for 48.2% of
      the samples. Sequence analysis showed that the most frequent species in these
      animals was Cryptosporidium ryanae, which was present in buffalo calves as young
      as 5 d. The zoonotic species Cryptosporidium parvum was detected in one animal.
      An uncommon Cryptosporidium 18S genotype was found in buffaloes.

PMID- 25941019
TI  - Rheumatologists' Views and Perceived Barriers to Using Patient Decision Aids in
      Clinical Practice.
AB  - OBJECTIVE: To explore rheumatologists' perceptions of patient decision aids
      (PtDAs) and identify barriers to using them in clinical practice. METHODS: A
      cross-sectional online survey of all members of the Canadian Rheumatology
      Association (CRA; n = 459) was conducted. We subsequently invited 10 respondents
      to participate in a 30-minute telephone interview to further explore their views
      on using PtDAs in clinical practice. Interview participants were purposefully
      sampled to achieve a balance in sex, years in clinical practice, and types of
      practice. RESULTS: In August and September 2013, 153 CRA members responded to the
      survey (response rate 33.3%); of those, 113 completed the entire questionnaire.
      Sixty-three respondents (55.8%) were male, 54 (47.8%) were >=50 years of age, and
      55 (48.7%) practiced in a multidisciplinary setting. When asked about their
      intention to use PtDAs, participants rated mean +/- SD 5.7 +/- 2.9 (where 0 = not
      likely and 10 = very likely). Sixty-four (56.6%) believed that rheumatologists
      were unfamiliar with PtDAs, and 76 (67.3%) thought that PtDAs would disturb their
      workflow. In-depth interviews revealed the following: the perception that PtDAs
      were no different from any other patient education tools, the concern that PtDAs
      were of limited value in real life since they relied solely on data from
      randomized controlled trials, and the fear that PtDAs could impair doctor-patient
      communication. CONCLUSION: There was a sense of ambivalence among rheumatologists
      about PtDAs. Our interviews further revealed concerns regarding the utility and
      benefits of PtDAs in clinical practice. The results show a need to familiarize
      physicians with PtDAs and to develop strategies to support their integration in
      clinical practice.

PMID- 25941020
TI  - A direct assessment of realized seed and pollen flow within and between two
      isolated populations of the food-deceptive orchid Orchis mascula.
AB  - Gene flow can counteract the loss of genetic diversity caused by genetic drift in
      small populations. For this reason, clearly understanding gene flow patterns is
      of the highest importance across fragmented landscapes. However, gene flow
      patterns are not only dependent upon the degree of spatial isolation of
      fragmented populations, but are also dependent upon the life-history traits of
      the species. Indeed, habitat fragmentation effects appear especially
      unpredictable for food-deceptive orchid species, because of their highly
      specialised seed and pollen dispersal mechanisms. In this study we used amplified
      fragment length polymorphism markers and subsequent parentage and spatial
      autocorrelation analysis to quantify the extent and the patterns of realized gene
      flow within and between two adjacent fragmented populations of the food-deceptive
      Orchis mascula. We observed considerable gene flow between both populations,
      occurring mainly through pollen dispersal. Seed dispersal, on the other hand, was
      mainly limited to the first few meters from the mother plant in both populations,
      although at least one among-population seed dispersal event was observed. This,
      in turn, resulted in a significant spatial genetic structure for both
      populations. Although genetic diversity was high in both populations and mainly
      outcrossing occurred, reproductive output was strongly skewed toward a limited
      number of successful adult plants. These observed patterns are likely due to the
      different pollinator behaviour associated with food-deceptive plants. We conclude
      that these populations can be considered viable under their current fragmented
      state. 

PMID- 25941021
TI  - Poorly differentiated hepatocellular carcinoma accompanied by anti-Hu antibody
      positive paraneoplastic peripheral neuropathy.
AB  - The anti-Hu antibody is one of the most famous onco-neural antibodies related to
      paraneoplastic neurological syndrome, and is associated with small cell lung
      carcinoma in most cases. Here, we report a case of poorly differentiated
      hepatocellular carcinoma accompanied by paraneoplastic peripheral neuropathy
      positive for the anti-Hu antibody. Image inspection before operation revealed
      that no tumors were found in organs other than the liver, including lung, and
      that the liver tumor had no metastatic lesion. The liver tumor showed
      histological appearance of poorly differentiated carcinoma with cartilaginous
      metaplasia and partial blastoid cell appearance. Most tumor cells presented
      trabecular-like structure lined by sinusoidal vessels. Immunohistochemically, the
      tumor cells were positive for low molecular weight cytokeratin and vimentin,
      partially positive for cytokeratin 19 and CD56, but negative for synaptophysin,
      chromogranin A and alpha-fetoprotein. Based on the trabecular-like morphology and
      the results of immunohistochemical staining, we concluded that the tumor was
      diagnosed as poorly differentiated hepatocellular carcinoma. Anti-Hu antibody
      positive paraneoplastic peripheral neuropathy accompanied with liver tumor is
      extremely rare as far as is known. The presented case indicates that poorly
      differentiated carcinoma has the potential to be the responsible lesion of anti
      Hu antibody-positive paraneoplastic neurological syndrome and systemic work-up is
      important for the management of this neurological disorder. 

PMID- 25941022
TI  - Expression of Critical Sulfur- and Iron-Oxidation Genes and the Community
      Dynamics During Bioleaching of Chalcopyrite Concentrate by Moderate Thermophiles.
AB  - Sulfate adenylyltransferase gene and 4Fe-4S ferredoxin gene are the key genes
      related to sulfur and iron oxidations during bioleaching system, respectively. In
      order to better understand the bioleaching and microorganism synergistic
      mechanism in chalcopyrite bioleaching by mixed culture of moderate thermophiles,
      expressions of the two energy metabolism genes and community dynamics of free and
      attached microorganisms were investigated. Specific primers were designed for
      real-time quantitative PCR to study the expression of these genes. Real-time PCR
      results showed that sulfate adenylyltransferase gene was more highly expressed in
      Sulfobacillus thermosulfidooxidans than that in Acidithiobacillus caldus, and
      expression of 4Fe-4S ferredoxin gene was higher in Ferroplasma thermophilum than
      that in S. thermosulfidooxidans and Leptospirillum ferriphilum. The results
      indicated that in the bioleaching system of chalcopyrite concentrate, sulfur and
      iron oxidations were mainly performed by S. thermosulfidooxidans and F.
      thermophilum, respectively. The community dynamics results revealed that S.
      thermosulfidooxidans took up the largest proportion during the whole period,
      followed by F. thermophilum, A. caldus, and L. ferriphilum. The CCA analysis
      showed that 4Fe-4S ferredoxin gene expression was mainly affected (positively
      correlated) by high pH and elevated concentration of ferrous ion, while no factor
      was observed to prominently influence the expression of sulfate
      adenylyltransferase gene. 

PMID- 25941023
TI  - Sanitizing Effect of Ethanol Against Biofilms Formed by Three Gram-Negative
      Pathogenic Bacteria.
AB  - Sanitizing effect of ethanol on a Yersinia enterocolitica biofilm was evaluated
      in terms of biomass removal and bactericidal activity. We found that 40 % ethanol
      was most effective for biofilm biomass removal; however, no significant
      difference was observed in bactericidal activity between treatment with 40 and 70
      % ethanol. This unexpected low ethanol concentration requirement for biomass
      removal was confirmed using biofilms of two additional pathogenic bacteria,
      Aeromonas hydrophila and Xanthomonas oryzae. Although only three pathogenic Gram
      negative bacteria were tested and the biofilm in nature was different from the
      biofilm in this study, the results in this study suggested the possible re
      evaluation of the effective sanitizing ethanol concentration 70 %, which is the
      concentration commonly employed for sanitization, on bacteria in a biofilm. 

PMID- 25941024
TI  - Genetic Variability of AdeRS Two-Component System Associated with Tigecycline
      Resistance in XDR-Acinetobacter baumannii Isolates.
AB  - The emergence of tigecycline resistance has increased in the last years. Although
      tigecycline-resistant Acinetobacter baumannii isolates were described all over
      the world, few reports regarding the molecular basis of this resistance are
      available. It has been recognized that the overexpression of AdeABC efflux pump
      is related to the tigecycline-resistant phenotype. In 37 clinical A. baumannii
      isolates we first determined the tigecycline-resistant phenotype and then, within
      a selected group, we analyzed the sequence of the adeRS operon, which is involved
      in the expression of the AdeABC efflux pump. Nucleotide sequence analysis of adeR
      and adeS showed the presence of 5 and 16 alleles, respectively. These results
      expose a high genetic variability in both genes, the adeS gene being more
      susceptible to genetic variation. The presence of 2 AdeR and 2 AdeS new variants
      were reported. Two of the new AdeRS variants were present in the intermediate and
      the resistant tigecycline A. baumannii isolates, suggesting a putative role in
      the development of the observed phenotype. More studies need to be addressed to
      determine the role of the genetic variability observed in the adeRS operon. 

PMID- 25941025
TI  - Fatal opioid poisoning: a counterfactual model to estimate the preventive effect
      of treatment for opioid use disorder in England.
AB  - AIM: A counterfactual model was used to estimate the number of fatal opioid
      related poisonings prevented by public treatment services for opioid use disorder
      (OUD) in England between April 2008 and March 2011. METHODS: Patient OUD
      treatment episode data recorded by the English National Drug Treatment Monitoring
      System were linked to data on opioid deaths recorded by the Office for National
      Statistics. The source population was the official estimate of non-medical opioid
      users (aged 15-64 years; approximately 260 000 each year). The target population
      was all individuals (aged 15-64 years) treated for OUD in the study period (n =
      220 665). The outcome measure was fatal opioid-related poisoning (opioid death).
      The opioid death rate [per 100 person-years (PY)] and mortality rate ratios (MRR)
      were computed for study year, age group (15-24, 25-34, 35-64 years) and for three
      treatment-related states: time spent 'prior to treatment', 'during treatment' and
      'after treatment'. RESULTS: Between April 2008 and March 2011, there were 3731
      opioid deaths in the study: 741 during treatment (0.20 per 100 PY; referent
      category); 2722 prior to treatment [0.77 per 100 PY; MRR = 3.76, 95% confidence
      interval (CI) = 3.18-4.44]; and 268 after treatment (0.41 per 100 PY; MRR = 1.99,
      95% CI = 1.64-2.41). By counterfactual estimation, national OUD treatment
      services prevented an average of 880 opioid deaths each year (95% CI = 702-1084).
      CONCLUSIONS: Between April 2008 and March 2011, a counterfactual model shows that
      the English public treatment system for opioid use disorder prevented an average
      of 880 deaths each year from opioid-related poisoning. Counterfactual models of
      mortality prevention can be used for outcome and performance monitoring of
      substance use disorder treatment systems.

PMID- 25941026
TI  - Emotion regulation in mothers and young children faced with trauma.
AB  - The present study investigated maternal emotion regulation as mediating the
      association between maternal posttraumatic stress symptoms and children's
      emotional dysregulation in a community sample of 431 Israeli mothers and children
      exposed to trauma. Little is known about the specific pathways through which
      maternal posttraumatic symptoms and deficits in emotion regulation contribute to
      emotional dysregulation. Inspired by the intergenerational process of relational
      posttraumatic stress disorder (PTSD), in which posttraumatic distress is
      transmitted from mothers to children, we suggest an analogous concept of
      relational emotion regulation, by which maternal emotion regulation problems may
      contribute to child emotion regulation deficits. Child emotion regulation
      problems were measured using the Child Behavior Checklist-Dysregulation Profile
      (CBCL-DP; T.M. Achenbach & I. Rescorla, 2000), which is comprised of three
      subscales of the CBCL: Attention, Aggression, and Anxiety/Depression. Maternal
      PTSD symptoms were assessed by the Posttraumatic Diagnostic Scale (E.B. Foa, L.
      Cashman, L. Jaycox, & K. Perry, 1997) and maternal emotion regulation by the
      Difficulties in Emotion Regulation Scale (K.L. Gratz & L. Roemer, 2004). Results
      showed that the child's emotion regulation problems were associated with both
      maternal posttraumatic symptoms and maternal emotion dysregulation. Further,
      maternal emotion regulation mediated the association between maternal
      posttraumatic symptoms and the child's regulation deficits. These findings
      highlight the central role of mothers' emotion regulation skills in the aftermath
      of trauma as it relates to children's emotion regulation skills. The degree of
      mothers' regulatory skills in the context of posttraumatic stress symptoms
      reflects a key process through which the intergenerational transmission of trauma
      may occur. Study results have critical implications for planning and developing
      clinical interventions geared toward the treatment of families in the aftermath
      of trauma and, in particular, the enhancement of mothers' emotion regulation
      skills after trauma. 

PMID- 25941027
TI  - Percutaneous Microwave Ablation of an Insulinoma in a Patient with Refractory
      Symptomatic Hypoglycemia.
AB  - Insulinomas are the most common functioning pancreatic neuroendocrine tumors
      (pNETs). Surgical excision is the preferred therapy, and medical treatment with
      diazoxide or octreotide is typically reserved for those who are poor surgical
      candidates. A recent emergence of minimally invasive treatment modalities has led
      to reports of successful radiofrequency and ethanol ablation of insulinomas. We
      report the first use of microwave ablation for treatment of an insulinoma in a
      patient with medical comorbidities contraindicating surgery. 

PMID- 25941029
TI  - Editorial.

PMID- 25941028
TI  - Visceral Obesity Predicts Fewer Lymph Node Metastases and Better Overall Survival
      in Colon Cancer.
AB  - BACKGROUND: The relationship between visceral obesity and colon cancer outcome
      has not been well studied. The goal of this study was to determine the impact of
      visceral obesity on lymph node (LN) metastasis and overall survival (OS) in colon
      cancer. MATERIALS AND METHODS: Metastatic LN ratio (MLR) was defined as the
      number of involved nodes by tumor divided by the total number of resected LNs.
      Visceral (VFA) and subcutaneous fat areas (SFA) were determined by measuring
      abdominal fat volume distribution via CT scan, and visceral obesity was defined
      as a VFA to total fat area ratio (V/T) > 0.29. RESULTS: In a multivariate
      analysis among 186 patients, there were inverse associations between V/T and MLR
      (OR = 0.413, 95% CI = 0.216-0.789, P = 0.007). Furthermore, patients with
      visceral obesity tended to have significantly better OS than patients with non
      visceral obesity. CONCLUSIONS: Higher V/T ratios which indicate referring to
      visceral obesity was significantly associated with decreased MLR and better OS
      for CRC.

PMID- 25941030
TI  - Prevalence of fetal alcohol syndrome in a South African city with a predominantly
      Black African population.
AB  - BACKGROUND: Fetal alcohol spectrum disorder (FASD) and fetal alcohol syndrome
      (FAS) are common in some South African populations, notably those of mixed
      ancestry descent in rural areas and small towns. Little is known about FAS/FASD
      prevalence in the majority of South Africans: city dwellers of Black African
      ethnicity. This study describes the prevalence of FAS in a South African city,
      comparing 2 suburbs with predominantly mixed ancestry (Roodepan) and Black
      African (Galeshewe) populations that house over 60% of the city population.
      METHODS: We conducted a tiered, active case ascertainment study for the
      prevalence of FAS and also detected some less clinically specific FASD cases. All
      first-grade learners in the 2 suburbs were eligible for anthropometric screening,
      and screen-positive learners were assessed for dysmorphic features of FAS. Those
      with suggestive clinical features received neurocognitive assessment, and
      maternal or collateral interview. Final diagnosis was made following a case
      conference. RESULTS: Complete ascertainment of FAS status was made in 1,503
      (94.7%) of 1,587 eligible learners (435 in Roodepan and 1,152 in Galeshewe).
      Overall, FAS was diagnosed in 83 (5.5%, 95% confidence interval [CI] = 4.4 to
      6.8) learners and FASD in 96 (6.4%, 95% CI = 5.2 to 7.7). Levels of FAS were high
      in both areas: 26 (6.3%, 95% CI = 4.2 to 9.2) learners from Roodepan, compared to
      57 (5.2%, 95% CI = 4.0 to 6.7) from Galeshewe (p = 0.39). No cases were
      previously diagnosed. The mortality rate for mothers of FASD children from
      Galeshewe was 19 of 65 (29%), compared to 3 of 31 (9.7%; p = 0.03) for Roodepan.
      Interviewed mothers in Galeshewe were older and had higher body mass index.
      CONCLUSIONS: Prevalence of FAS is high in both Galeshewe and Roodepan, and the
      lack of prior diagnoses indicates that awareness remains low. The maternal
      mortality rate was especially high in Galeshewe. The unexpectedly high burden of
      FAS in an urban area with predominantly Black African population mandates
      extension of surveillance and intervention measures in southern Africa.

PMID- 25941031
TI  - Tumor necrosis factor and interleukin-6 differentially regulate Dkk-1 in the
      inflamed arthritic joint.
AB  - OBJECTIVE: Tumor necrosis factor (TNF) drives bone destruction, but it also
      inhibits new bone formation by inducing Dkk-1, an inhibitor of the Wnt pathway.
      Accordingly, blocking of Dkk-1 reverses the phenotype in experimental arthritis
      from a pattern of bone destruction to a pattern of bone formation. To delineate
      the potential role of Dkk-1 in the structural phenotype of human arthritis, we
      analyzed the expression of Dkk-1 and its regulation by proinflammatory cytokines
      in the inflamed peripheral joints of patients with spondyloarthritis (SpA) and
      rheumatoid arthritis (RA). METHODS: Expression of Dkk-1 and proinflammatory
      cytokines was determined by enzyme-linked immunosorbent assay and microarray
      analysis in synovial fluid (SF) and synovial tissue, respectively. Regulation of
      Dkk-1 production by proinflammatory cytokines was assessed in fibroblast-like
      synoviocyte (FLS) cultures. RESULTS: TNF and interleukin-1beta (IL-1beta) levels,
      were higher in RA SF than in SpA SF (P < 0.001 for both), whereas levels of IL-6
      were not. Levels of Dkk-1 were similar in SpA SF and RA SF and were not
      correlated with TNF and IL-1beta levels. However, Dkk-1 levels showed an inverse
      correlation with IL-6 levels in both SpA SF (r = -0.31, P = 0.04) and RA SF (r = 
      0.39, P = 0.01); this result was reproduced at the messenger RNA level in
      synovial tissue. In vitro experiments with FLS confirmed that Dkk-1 production
      was strongly induced by TNF but clearly suppressed by IL-6. Moreover, IL-6 was
      able to suppress the TNF-induced up-regulation of Dkk-1 production by FLS.
      CONCLUSION: The inverse correlation of Dkk-1 levels with IL-6 levels observed in
      vivo in the inflamed joints was mirrored by the differential regulation of Dkk-1
      production by TNF and IL-6 in vitro. The relative balance between these and other
      factors in the arthritic joints may determine functional Wnt signaling and tissue
      remodeling.

PMID- 25941032
TI  - Novel fusion between the breakpoint cluster region and platelet-derived growth
      factor receptor-alpha genes in a patient with chronic myeloid leukemia-like
      neoplasm: undetectable residual disease after imatinib therapy.
AB  - Rare patients suffering from myeloid neoplasms share clinical and cytological
      features indistinguishable from chronic myeloid leukemia (CML) but lack the BCR
      ABL1 fusion gene. Several studies provide evidence that alterations in genes
      encoding tyrosine kinase receptors such as the platelet-derived growth factor
      receptor (PDGFR) may be involved in the pathogenesis of these disorders. Here we
      describe a patient with a rare CML-like disease in whom we identified a novel in
      frame BCR-PDGFRA rearrangement joining BCR exon 17 to PDGFRA exon 13, resulting
      in overexpression of PDGFRA. The design of a specific quantitative PCR assay to
      monitor the molecular response during treatment with imatinib, a multitargeted
      tyrosine kinase inhibitor (TKI) with activity against ABL, c-Kit, and PDGFRA
      revealed an outstanding disease control with durably undetectable BCR-PDGFRA
      transcripts. Multiple TKIs are currently available yet with distinct target
      profiles; thus, accurate molecular diagnosis and monitoring tools are essential
      to establish tailored treatments and assess response to therapy in this type of
      rare hematological malignancy. 

PMID- 25941034
TI  - Pyrite (FeS2) nanocrystals as inexpensive high-performance lithium-ion cathode
      and sodium-ion anode materials.
AB  - In light of the impeding depletion of fossil fuels and necessity to lower carbon
      dioxide emissions, economically viable high-performance batteries are urgently
      needed for numerous applications ranging from electric cars to stationary large
      scale electricity storage. Due to its low raw material cost, non-toxicity and
      potentially high charge-storage capacity pyrite (FeS2) is a highly promising
      material for such next-generation batteries. In this work we present the
      electrochemical performance of FeS2 nanocrystals (NCs) as lithium-ion and sodium
      ion storage materials. First, we show that nanoscopic FeS2 is a promising lithium
      ion cathode material, delivering a capacity of 715 mA h g(-1) and average energy
      density of 1237 Wh kg(-1) for 100 cycles, twice higher than for commonly used
      LiCoO2 cathodes. Then we demonstrate, for the first time, that FeS2 NCs can serve
      as highly reversible sodium-ion anode material with long cycling life. As sodium
      ion anode material, FeS2 NCs provide capacities above 500 mA h g(-1) for 400
      cycles at a current rate of 1000 mA g(-1). In all our tests and control
      experiments, the performance of chemically synthesized nanoscale FeS2 clearly
      surpasses bulk FeS2 as well as large number of other nanostructured metal
      sulfides. 

PMID- 25941033
TI  - Dual-energy CT after radiofrequency ablation of liver, kidney, and lung lesions:
      a review of features.
AB  - Early detection of residual tumour and local tumour progression (LTP) after
      radiofrequency (RF) ablation is crucial in the decision whether or not to re
      ablate. In general, standard contrast-enhanced computed tomography (CT) is used
      to evaluate the technique effectiveness; however, it is difficult to
      differentiate post-treatment changes from residual tumour. Dual-energy CT (DECT)
      is a relatively new technique that enables more specific tissue characterisation
      of iodine-enhanced structures because of the isolation of iodine in the imaging
      data. Necrotic post-ablation zones can be depicted as avascular regions by DECT
      on greyscale- and colour-coded iodine images. Synthesised monochromatic images
      from dual-energy CT with spectral analysis can be used to select the optimal keV
      to achieve the highest contrast-to-noise ratio between tissues. This facilitates
      outlining the interface between the ablation zone and surrounding tissue. Post
      processing of DECT data can lead to an improved characterisation and delineation
      of benign post-ablation changes from LTP. Radiologists need to be familiar with
      typical post-ablation image interpretations when using DECT techniques. Here, we
      review the spectrum of changes after RF ablation of liver, kidney, and lung
      lesions using single-source DECT imaging, with the emphasis on the additional
      information obtained and pitfalls encountered with this relatively new technique.
      Teaching Points *Technical success of RF ablation means complete destruction of
      the tumour. *Assessment of residual tumour on contrast-enhanced CT is hindered by
      post-ablative changes. *DECT improves material differentiation and may improve
      focal lesion characterisation. *Iodine maps delineate the treated area from the
      surrounding parenchyma well. 

PMID- 25941035
TI  - Editorial Comment to Prognostic value of preoperative pyuria in patients with non
      muscle-invasive bladder cancer.

PMID- 25941036
TI  - Long-lived states in an intrinsically disordered protein domain.
AB  - Long-lived states (LLS) are relaxation-favored spin population distributions of J
      coupled magnetic nuclei. LLS were measured, along with classical (1)H and (15)N
      relaxation rate constants, in amino acids of the N-terminal Unique domain of the
      c-Src kinase, which is disordered in vitro under physiological conditions. The
      relaxation rates of LLS can probe motions and interactions in biomolecules. LLS
      of the aliphatic protons of glycines, with lifetimes approximately four times
      longer than their spin-lattice relaxation times, are reported for the first time
      in an intrinsically disordered protein domain. LLS relaxation experiments were
      integrated with 2D spectroscopy methods, further adapting them for studies on
      proteins.

PMID- 25941037
TI  - Diffusion control of an ion by another in LiNbO3 and LiTaO3 crystals.
AB  - Diffusion-doping is an effective, practical method to improve material properties
      and widen material application. Here, we demonstrate a new physical phenomenon:
      diffusion control of an ion by another in LiNbO3 and LiTaO3 crystals. We
      exemplify Ti(4+)/X(n+) (X(n+) = Sc(3+), Zr(4+), Er(3+)) co-diffusion in the
      widely studied LiNbO3 and LiTaO3 crystals. Some Ti(4+)/X(n+)-co-doped LiNbO3 and
      LiTaO3 plates were prepared by co-diffusion of stacked Ti-metal and Er-metal
      (Sc2O3 or ZrO2) films coated onto LiNbO3 or LiTaO3 substrates. The Ti(4+)/X(n+)
      co-diffusion characteristics were studied by secondary ion mass spectrometry. In
      the X(n+)-only diffusion case, the X(n+) diffuses considerably slower than the
      Ti(4+). In the Ti(4+)/X(n+) co-diffusion case, the faster Ti(4+) controls the
      diffusion of the slower X(n+). The X(n+) diffusivity increases linearly with the
      initial Ti-metal thickness and the increase depends on the X(n+) species. The
      phenomenon is ascribed to the generation of additional defects induced by the
      diffusion of faster Ti(4+) ions, which favors and assists the subsequent
      diffusion of slower X(n+) ion. For the diffusion system studied here, it can be
      utilized to substantially shorten device fabrication period, improve device
      performance and produce new materials. 

PMID- 25941038
TI  - CBP-Dependent memory consolidation in the prefrontal cortex supports object
      location learning.
AB  - Recognition of an object's location in space is supported by hippocampus
      dependent recollection. Converging evidence strongly suggests that the interplay
      between the prefrontal cortex and hippocampus is critical for spatial memory.
      Lesion, pharmacological, and genetic studies have been successful in dissecting
      the role of plasticity in the hippocampal circuit in a variety of neural
      processes relevant to spatial memory, including memory for the location of
      objects. However, prefrontal mechanisms underlying spatial memory are less well
      understood. Here, we show that an acute hypofunction of the cyclic-AMP regulatory
      element binding protein (CREB) Binding Protein (CBP) histone acetyltransferase
      (HAT) in the medial prefrontal cortex (mPFC) results in delay-dependent
      disruption of object-location memory. These data suggest that mechanisms
      involving CBP HAT-mediated lysine acetylation of nuclear proteins support
      selectively long-term encoding in the mPFC circuits. Evidence from the object
      location task suggests that long-term memory encoding within the mPFC complements
      hippocampus-dependent spatial memory mechanisms and may be critical for broader
      network integration of information necessary for an assessment of subtle spatial
      differences to guide appropriate behavioral response during retrieval of spatial
      memories.

PMID- 25941040
TI  - Examination of the Relationship Between Autonomy and English Achievement as
      Mediated by Foreign Language Classroom Anxiety.
AB  - This study investigated the relationship between autonomy and English language
      achievement among third-grade high school students as mediated by foreign
      language classroom anxiety in a city in the north-west of Iran. A sample of 400
      students (187 males, and 213 females) was assessed for their levels of autonomy
      and foreign language anxiety using the Autonomy Questionnaire and Foreign
      Language Classroom Anxiety Scale (FLCAS), respectively. Participants' scores on
      their final English exam were also used as the measurement of their English
      achievement. The results of Pearson correlation revealed a strong correlation
      between learners' autonomy and their English achievement (r [Formula: see text]
      .406, n [Formula: see text] 400, [Formula: see text]). Also, foreign language
      classroom anxiety was found to be significantly and negatively correlated with
      English achievement (r [Formula: see text] [Formula: see text].472, n [Formula:
      see text] 400, [Formula: see text]). Hierarchical multiple regression was used to
      assess the ability of autonomy to predict language learning achievement, after
      controlling for the influence of anxiety. In sum, the results of hierarchical
      multiple regressions revealed that foreign language classroom anxiety
      significantly mediates the relationship between autonomy and English language
      achievement. Implications for both teachers and learners, and suggestions for
      further research are provided. 

PMID- 25941039
TI  - Age-related macular degeneration and mortality in older women: the study of
      osteoporotic fractures.
AB  - OBJECTIVES: To examine the association between age-related macular degeneration
      (AMD) and all-cause and cause-specific mortality in a population of older women.
      DESIGN: Prospective cohort study. SETTING: Four U.S. clinical centers.
      PARTICIPANTS: A random sample of 1,202 women with graded fundus photographs at
      the Year 10 visit of the Study of Osteoporotic Fractures (mean age 79.5).
      MEASUREMENTS: Forty-five-degree stereoscopic fundus photographs were graded for
      presence and severity (early vs late) of AMD. Vital status was adjudicated from
      death certificates. Cox proportional hazards models, adjusted for appropriate
      confounders, were used to estimate mortality hazards ratios. RESULTS: Prevalence
      of any AMD was 40.5% at baseline, with 441 (36.7%) having early AMD and 46 (3.8%)
      having late AMD. Cumulative mortality was 51.6% over 15 years of follow-up.
      Overall, there was no significant association between AMD presence or severity
      and all-cause or cause-specific mortality. Because there was a significant
      interaction between AMD and age in predicting mortality (P<.05 for each mortality
      type), analyses were stratified according to age group. In women younger than 80,
      after adjusting for covariates, late AMD was associated with cardiovascular
      disease (CVD) mortality (hazard ratio (HR)=2.61, 95% confidence interval
      (CI)=1.05-6.46). In women aged 80 and older, early AMD was associated with all
      cause (HR=1.39, 95% CI=1.11-1.75) and non-CVD, noncancer (HR=1.45, 95% CI=1.05
      2.00) mortality. Any AMD was associated with all-cause (HR=1.42, 95% CI=1.13
      1.78) and CVD (HR=1.45, 95% CI=1.01-2.09) mortality in women aged 80 and older.
      CONCLUSION: AMD is a predictor of poorer survival in women, especially those aged
      80 and older. Determination of shared risk factors may identify novel pathways
      for intervention that may reduce the risk of both conditions.

PMID- 25941041
TI  - Lifestyle, attitudes and needs of uncured XDR-TB patients living in the
      communities of South Africa: a qualitative study.
AB  - OBJECTIVE: Patient-level data are required to inform strategies interrupting
      transmission and default in patients with extensively drug-resistant TB (XDR-TB)
      to improve models of care and identify potential routes of transmission. We
      therefore explored the experiences, lifestyle, attitudes and needs of patients
      with uncured XDR-TB, who failed or interrupted therapy, living without treatment
      in the community. METHODS: We conducted in-depth interviews with 12 community
      based patients from South Africa. Family members were interviewed when patients
      were unavailable. Interviews were analysed using inductive thematic analysis.
      RESULTS: The thematic experiences identified from the interviews were as follows:
      (i) living with but not being cured of XDR-TB, (ii) altered lifestyle in the
      community, (iii) experiences with community health care, (iv) local community
      members, and (v) wants and needs. Patients identified mistrust in health care,
      futility of treatment regimens, a need for a purpose in life and subsistence as
      major concerns. Restriction of living in the community for patients whose
      treatment had failed resulted in self-imposed isolation. Defaulters focused more
      on the never-ending drug regimen and bad experiences with health care
      contributing to non-adherence. Family members emphasised an under-recognised
      experience of unforeseen burden, obligation, worry and discomfort. Lack of
      knowledge and lack of concern about transmission was evident. CONCLUSION: Current
      models of care are not adequately meeting the needs of patients with uncured XDR
      TB and relatives. These data inform the need for community-based palliative care,
      vocational facilities to improve economic opportunities, home-based infection
      control and improved psychosocial support to increase patient adherence, reduce
      transmission, provide income and relieve the burden on family members.

PMID- 25941042
TI  - Design, synthesis, and biological evaluation of scutellarein carbamate
      derivatives as potential multifunctional agents for the treatment of Alzheimer's
      disease.
AB  - A series of scutellarein carbamate derivatives were designed and synthesized
      based on the multitarget-directed drug design strategy for treatment of
      Alzheimer's disease. Their acetylcholinesterase and butyrylcholinesterase
      inhibitory activities, antioxidant activities, metals chelation, and
      neuroprotective effects against hydrogen peroxide-induced PC12 cell injury were
      evaluated in vitro. The preliminary results indicated that compound 7b exhibited
      good inhibitory potency toward AChE and BuChE with IC50 values of 1.2 +/- 0.03
      MUm and 22.1 +/- 0.15 MUm, respectively, possessed the strong antioxidant potency
      (10.3 trolox equivalents), as well as acted as a selective metal chelator and
      neuroprotective agent. Furthermore, 7b could improve memory impairment induced by
      scopolamine, ethanol, and sodium nitrite using the step-down passive avoidance
      task in vivo and could remarkably decrease the activity of acetylcholinesterase
      in mice brain. This study indicated that 7b could be considered as a potential
      multitarget agent against AD. 

PMID- 25941043
TI  - Patellar instability: CT and MRI measurements and their correlation with internal
      derangement findings.
AB  - PURPOSE: To test the inter-observer and inter-method reliability among the
      measures suggesting patellofemoral joint disorder on both CT and MRI in the same
      subject and find possible association with internal derangements of the
      patellofemoral joint on MRI. METHODS: Institutional review board approval was
      obtained with waiver of the informed consent in this HIPPA-compliant study. CT
      and MRI were evaluated in 32 knees in 32 respective subjects (10 men/22 women,
      mean age 38 +/- 19 years). Three trained observers assessed tibial tuberosity
      trochlear groove (TT-TG) distance, trochlear angle and trochlear depth on both CT
      and MRI. Intra-class correlation coefficient (ICC) was used to evaluate inter
      observer and inter-method reliability. Two radiologists' consensus reading was
      used to evaluate their association with soft tissue abnormalities of the
      patellofemoral joint. Chi-square test was used to assess the statistical
      significance of the qualitative variables. RESULTS: There was an excellent inter
      observer reliability (ICC for CT >0.89 and for MRI >0.90) and inter-method
      reliability (ICC >0.86) for all the quantitative measurements. There was a
      significant association between increased TT-TG distance value on MR imaging and
      lateral facet patellar cartilage abnormality and joint effusion (p < 0.05).
      CONCLUSION: Quantitative trochlear parameters can be reliably calculated on MRI,
      and an abnormal TT-TG distance is the most useful measurement among various
      static MR imaging parameters to correlate with patellar chondrosis and joint
      effusion. TT-TG distance should be reported in patellofemoral pain syndrome
      patients. LEVEL OF EVIDENCE: IV.

PMID- 25941046
TI  - Processes of user participation among formal and family caregivers in home-based
      care for persons with dementia.
AB  - Scandinavian health policy supports prolonged home-based care for people with
      dementia. User participation is expected to reduce family burden. The aim of this
      study was to explore how formal and family caregivers experience collaboration
      while providing home-based dementia care, with a focus on user participation.
      Seventeen qualitative in-depth interviews were conducted among formal and family
      caregivers in rural municipalities. The theme identified during this process was
      'negotiating participation in decisions'. This theme was analysed using
      positioning theory. Concepts such as user participation are ambiguous, and
      caregivers negotiate positions during decision-making processes. Such
      negotiations are caused by the problematic relationships among patients' legal
      consent, undefined spokespersons and pragmatic care practices. These constant
      negotiations enable or obstruct collaboration in several situations. User
      participation as a concept might contribute to conflicts during collaborations.
      Dialogues about user participation that focus on consent and spokespersons could
      reduce the burden created by negotiations in practice.

PMID- 25941044
TI  - Anterolateral rotatory instability of the knee.
AB  - Recent publications have generated renewed interest in the anatomy of the
      anterolateral capsule. Knowledge of the biomechanical function of the
      anterolateral components is lacking. Further research is required to evaluate the
      influence of the anterolateral capsule on rotatory laxity of the knee. The role
      of surgical procedures, such as an extra-articular tenodesis or lateral plasty,
      has to be defined based on quantification of the injury. This article seeks to
      summarize the current literature and discusses the role of the anterolateral
      capsule and reconstructive techniques in combined ligamentous knee trauma. Level
      of evidence V. 

PMID- 25941045
TI  - The Kind of Student You Were in Elementary School Predicts Mortality.
AB  - We examined the association of self-reported and teacher-rated student
      characteristics assessed at the end of primary school with all-cause mortality
      assessed through age 52. Data stem from a representative sample of students from
      Luxembourg assessed in 1968 (N = 2,543; M = 11.9 years, SD = 0.6; 49.9% female; N
      = 166 participants died). Results from logistic regression analyses showed that
      the self-reported responsible student scale (OR = .81; CI = [.70; .95]) and the
      teacher rating of studiousness (OR = .80; CI = [.67; .96]) were predictive for
      all-cause mortality even after controlling for IQ, parental SES, and sex. These
      findings indicate that both observer-rated and self-reported student behaviors
      are important life-course predictors for mortality and are perhaps more important
      than childhood IQ.

PMID- 25941047
TI  - How do people in the early stage of Alzheimer's disease see their future?
AB  - Older people fear Alzheimer's disease. Central to the fear of the disease is the
      dread of the loss of identity or self. The aim of this study is to investigate
      the thoughts people in an early stage of Alzheimer's disease have about their
      future selves, and the consequences these thoughts have for their temporary
      lives. The concepts of future and self are understood in terms of the concepts
      'possible selves' and 'selfhood'. The participants in the study are two men in
      their early 60 s. The data consist of four individual interviews and 11
      facilitated family conversations including two of their next of kin. The data
      were collected over a two-year period. The data were interpreted using a
      hermeneutic analysis inspired by Gadamer. The main findings were the efforts made
      by the participants to live in the present and their worries about a future as
      'living dead'.

PMID- 25941048
TI  - The first world war drives rehabilitation toward the modern concepts of
      disability and participation.
AB  - The First World War produced a huge number of disabled soldiers. During the war,
      surgeons realized that it was not enough to merely treat the limbs of the wounded
      soldiers; it was also necessary to train them to use their remaining abilities to
      their greatest capacity. Governments at the same time realized that such a high
      number of veterans created a financial burden, by entitling disabled veterans to
      full healthcare, raising the issues of social welfare. Both in the US and Europe,
      programs of rehabilitation were instituted, providing injured soldiers with long
      term medical care and vocational training aimed at restituting soldier's
      independence for a speedy return to work. In Italy at the Istituto Ortopedico
      Rizzoli, one of the most renowned Hospitals for the treatment of orthopedic
      deformities, Putti set up a technologically advanced Orthopedic Workshop, and a
      Rehabilitation House. The so called "reconstruction programs" addressed all
      aspects of rehabilitation (including physiotherapy, curative workshops and
      vocational therapy), seeing disability in terms of function. The experience
      gained in the treatment of war victims markedly enriched rehabilitation
      techniques, but overall the First World War helped engender the concept of
      rehabilitative programs to assist disabled veterans reintegrate in the workplace,
      thus laying the foundations of the modern concept of participation at a social
      level. In the centenary of Italy's entry into the First World War, it is worth
      underlining just how much hindsight affords us a new perspective on Physical
      Medicine and Rehabilitation. It reminds us that rehabilitation is not merely the
      role of medicine, but forms part of a multifaceted approach involving societal
      roles and expectations, regardless of the psychological and physical impairments
      suffered by the individuals concerned. 

PMID- 25941050
TI  - Reply from authors re: Robert S. Svatek. Long-term outcomes of the FinnBladder-4
      study. Eur Urol 2015;68:618-9: which type of maintenance matters?

PMID- 25941049
TI  - Survivorship and improving quality of life in men with prostate cancer.
AB  - CONTEXT: Long-term survival following a diagnosis of cancer is improving in
      developed nations. However, living longer does not necessarily equate to living
      well. OBJECTIVE: To search systematically and synthesise narratively the evidence
      from randomised controlled trials (RCTs) of supportive interventions designed to
      improve prostate cancer (PCa)-specific quality of life (QoL). EVIDENCE
      ACQUISITION: A systematic search of Medline and Embase was carried out from
      inception to July 2014 to identify interventions targeting PCa QoL outcomes. We
      did not include nonrandomised studies or trials of mixed cancer groups. In
      addition to database searches, citations from included papers were hand-searched
      for any potentially eligible trials. EVIDENCE SYNTHESIS: A total of 2654 PCa
      survivors from 20 eligible RCTs were identified from our database searches and
      reference checks. Disease-specific QoL was assessed most frequently by the
      Functional Assessment of Cancer Therapy-Prostate questionnaire. Included studies
      involved men across all stages of disease. Supportive interventions that featured
      individually tailored approaches and supportive interaction with dedicated staff
      produced the most convincing evidence of a benefit for PCa-specific QoL. Much of
      these data come from lifestyle interventions. Our review found little supportive
      evidence for simple literature provision (either in booklets or via online
      platforms) or cognitive behavioural approaches. CONCLUSIONS: Physical and
      psychological health problems can have a serious negative impact on QoL in PCa
      survivors. Individually tailored supportive interventions such as exercise
      prescription/referral should be considered by multidisciplinary clinical teams
      where available. Cost-effectiveness data and an understanding of how to sustain
      benefits over the long term are important areas for future research. PATIENT
      SUMMARY: This review of supportive interventions for improving quality of life in
      prostate cancer survivors found that supervised and individually tailored patient
      centred interventions such as lifestyle programmes are of benefit.

PMID- 25941051
TI  - HIV pre-test information, discussion or counselling? A review of guidance
      relevant to the WHO European Region.
AB  - In the context of a shift from exceptionalism to normalisation, this study
      examines recommendations/evidence in current pan-European/global guidelines
      regarding pre-test HIV testing and counselling practices in health care settings.
      It also reviews new research not yet included in guidelines. There is consensus
      that verbal informed consent must be gained prior to testing, individually, in
      private, confidentially, in the presence of a health care provider. All
      guidelines recommend pre-test information/discussion delivered verbally or via
      other methods (information sheet). There is agreement about a minimum standard of
      information to be provided before a test, but guidelines differ regarding
      discussion about issues encouraging patients to think about implications of the
      result. There is heavy reliance on expert consultation in guideline development.
      Referenced scientific evidence is often more than ten years old and based on
      US/UK research. Eight new papers are reviewed. Current HIV testing and
      counselling guidelines have inconsistencies regarding the extent and type of
      information that is recommended during pre-test discussions. The lack of new
      research underscores a need for new evidence from a range of European settings to
      support the process of expert consultation in guideline development. 

PMID- 25941052
TI  - Outcomes of on-site antiretroviral therapy provision in a South African
      correctional facility.
AB  - We evaluated a novel on-site antiretroviral therapy (ART) programme in a South
      African correctional facility using routinely collected programme data, from a
      retrospective cohort of adult inmates starting ART between 03/2007 and 03/2009
      followed-up to 09/2009. We report (1) mortality (using survival analysis); (2)
      retention in the programme (to 09/2009); and (3) virological suppression at six
      and 12 months (<400 copies/ml) following ART initiation. In total, 404 started
      ART (median age 33 years; 91.3% men; median baseline CD4 cell count 152 cells/ul
      [interquartile range 85-225]). Among 299 starting ART for the first time (ART
      naive), 23 deaths occurred during 252 person-years (median follow-up nine
      months). Mortality rates were 17.2 at 0-6 months (95% confidence interval 10.9
      26.9) and 2.8 at >6 months (95% confidence interval 1.1-7.5)/100 person-years; p
      < 0.001. At 09/2009, 35.6% (144/404) remained in the correctional facility, with
      94.4% (136/144) retained in the programme; 38.4% (155/404) were released; and
      20.0% (81/404) transferred to another facility. ART-naive patients in care six
      and 12 months after ART initiation, 94.7% (124/131) and 92.5% (74/80) were
      virologically suppressed, respectively. High early mortality warrants the early
      identification and management of HIV-positive inmates. The high mobility of
      inmates necessitates systems for facilitating continuity of care. Good
      virological responses and retention supports decentralising HIV care to
      correctional facilities.

PMID- 25941054
TI  - HIV infection presenting proliferation of CD8+ T lymphocyte and hemophagocytic
      lymphohistiocytosis.
AB  - Hemophagocytic lymphohistiocytosis is a rare hyperinflammatory disorder
      characterised by CD8+ T lymphocyte activation and hypercytokinemia. Autoimmune
      disorders including hemophagocytic lymphohistiocytosis have been described in HIV
      patients; however, it is a rare initial presentation of HIV infection. We present
      an unusual case of HIV infection presenting with hemophagocytic
      lymphohistiocytosis.

PMID- 25941053
TI  - Sexually transmitted infection screening uptake and knowledge of sexually
      transmitted infection symptoms among female sex workers participating in a
      community randomised trial in Peru.
AB  - This study aims to evaluate condom use, sexually transmitted infection (STI)
      screening, and knowledge of STI symptoms among female sex workers in Peru
      associated with sex work venues and a community randomised trial of STI control.
      One component of the Peru PREVEN intervention conducted mobile-team outreach to
      female sex workers to reduce STIs and increase condom use and access to
      government clinics for STI screening and evaluation. Prevalence ratios were
      calculated using multivariate Poisson regression models with robust standard
      errors, clustering by city. As-treated analyses were conducted to assess outcomes
      associated with reported exposure to the intervention. Care-seeking was more
      frequent in intervention communities, but differences were not statistically
      significant. Female sex workers reporting exposure to the intervention had a
      significantly higher likelihood of condom use, STI screening at public health
      clinics, and symptom recognition compared to those not exposed. Compared with
      street- or bar-based female sex workers, brothel-based female sex workers
      reported significantly higher rates of condom use with last client, recent
      screening exams for STIs, and HIV testing. Brothel-based female sex workers also
      more often reported knowledge of STIs and recognition of STI symptoms in women
      and in men. Interventions to promote STI detection and prevention among female
      sex workers in Peru should consider structural or regulatory factors related to
      sex work venues.

PMID- 25941055
TI  - Evaluation of patient care cascade for HIV-positive patients diagnosed in La
      Romana, Dominican Republic in 2011: a retrospective cohort study.
AB  - The Caribbean has the highest adult HIV prevalence in the world after sub-Saharan
      Africa (2011). One sub-population in the Dominican Republic is the migratory
      Batey community primarily comprised of Haitian immigrants with limited access to
      healthcare and HIV prevalence rates of between 3.0% and 9.0%, compared to 0.7%
      nationally. This retrospective cohort study describes the cumulative retention
      from diagnosis to virological suppression for newly-diagnosed HIV-infected adults
      presenting to the Clinica de Familia and its Batey programme in La Romana, during
      2011. Of the patients diagnosed with HIV, 65% entered into care, 59% completed
      immunologic testing, 53% were eligible for antiretroviral therapy (ART)
      initiation, 36% initiated ART within three months of eligibility and 27% were
      retained in care. Seventeen per cent of those retained on ART with a 12-month
      viral load measure had undetectable viral load. Attrition primarily occurred
      before ART initiation. The Batey programme had a first step lost-to-follow-up of
      88% compared to 20% at the clinic (p < 0.001). This retrospective study details
      the continuum of care and indicates where structural changes must occur to
      increase continuity between steps. The manuscript results are important to help
      implement programmes to enhance engagement and retention in HIV primary care. 

PMID- 25941056
TI  - Candida species bloodstream infections in hospitalised children: A 10-year
      experience.
AB  - In a 10-year retrospective study we assessed the epidemiology of candidemia and
      the association between the presence and removal of indwelling central venous
      catheters, antifungal use and clinical outcomes among hospitalised children.
      Demographic and clinical information were retrieved from the electronic medical
      records. One hundred six episodes of candidemia were identified in 83 unique
      patients. Candida parapsilosis was the most prevalent (52%) species, followed by
      C. albicans (25%). Non-oncologic children receiving fluconazole within 30 days of
      developing candidemia were most likely to develop C. parapsilosis infection (40%,
      P = 0.006), independent of total parenteral nutrition (odds ratio (OR) 2.5, 95%
      confidence interval (CI): 0.6-11, P = 0.3). Crude mortality rate was 12% and
      significantly higher for children less than 2 years (OR: 6.7, 95% CI: 1.9-23, P =
      0.003), and those infected with C. lusitaniae (OR: 9, 95% CI: 1.6-51, P = 0.02).
      The aggregate use of antifungal agents decreased overtime (chi(2) : 16.7, P <
      0.0001). Fluconazole remained the most common antifungal agent used during the
      study. 

PMID- 25941058
TI  - Genetics: Increased prevalence of large genomic imbalances among children with
      chronic kidney disease.

PMID- 25941059
TI  - Transplantation: The vexing challenges of deceased donor organ allocation.

PMID- 25941061
TI  - Cardiovascular disease: Questioning the effect of beta-blockers on vascular
      stiffness.

PMID- 25941062
TI  - Association of BAFF and IL-17A with subphenotypes of primary Sjogren's syndrome.
AB  - AIM: Primary Sjogren's syndrome (pSS) is an autoimmune disease affecting exocrine
      glands. Both autoreactive T cells and B cells are involved in the development of
      pSS, but their exact contribution to the pathogenesis is not clear. Here, we
      aimed to investigate the association of B-cell activating factor (BAFF) and
      interleukin (IL)-17A with subphenotypes of pSS. METHODS: Peripheral blood samples
      were collected from 31 pSS patients and 28 healthy controls. The serum levels of
      BAFF and IL-17A were quantified by sandwich ELISA. RESULTS: The increased
      circulating BAFF levels are associated with higher immunoglobulin G (IgG) levels
      (P = 0.0167) and anti-Ro/SS antigen A autoantibody (P = 0.032), while the
      elevated circulating levels of IL-17A are associated with lower C3 levels (P =
      0.0213) and higher focus score of salivary gland tissue (P = 0.002). CONCLUSION:
      Our results show that BAFF and IL-17A are associated with different subphenotypes
      of pSS, suggesting both humoral and cellular immune response are involved in the
      pathogenesis of pSS.

PMID- 25941063
TI  - Thrombotic risk in patients with immune haemolytic anaemia.

PMID- 25941060
TI  - Long-term medical risks to the living kidney donor.
AB  - Living kidney donation benefits recipients and society but carries short-term and
      long-term risks for the donor. This Review summarizes the studies that underlie
      our current understanding of these risks in the first decade after donation, with
      a view to improving the informed consent process. Two studies report a higher
      risk of end-stage renal disease (ESRD) among donors than among healthy nondonors;
      however, the absolute 15-year incidence of ESRD is <1%. All-cause mortality and
      the risk of cardiovascular events are similar among donors and healthy nondonors,
      although one study provides evidence for a 5% increase in all-cause mortality
      after 25 years that is attributable to donation. Some evidence suggests that the
      20-year incidence of gout is slightly higher among donors than among healthy
      nondonors. The risks of gestational hypertension or pre-eclampsia seem to be 6%
      higher in pregnancies among donors than in pregnancies among healthy nondonors.
      The incidences of acute kidney injury, kidney stones that require surgical
      intervention, gastrointestinal bleeding and fractures seem no higher among donors
      than among healthy nondonors, although some of these conclusions are based on a
      small number of events. Future studies must clarify the lifetime incidence of
      long-term outcomes, particularly in relation to a donor's age, race, and history
      of comorbidities. 

PMID- 25941064
TI  - Repetitive jumping and sprinting until exhaustion alters hamstring reflex
      responses and tibial translation in males and females.
AB  - The incidence of anterior cruciate ligament injuries is considerably higher in
      females than in males and the underlying mechanisms are still under debate.
      Research indicates that the neuromuscular system of females and males might
      respond differently to the same fatigue protocol due to differences in muscle
      activation during movement tasks. This study analyzed sex differences in
      hamstring reflex responses and posterior-anterior tibial translation (TT) before
      and after fatiguing exercise. We measured the isolated movement of the tibia
      relative to the femur as a consequence of mechanically induced TT in standing
      subjects as well as muscle activity of the hamstrings before and after repetitive
      jumping and sprinting until exhaustion. Muscle fatigue delayed reflex onset
      latencies in females and males. A reduction in reflex responses associated with
      an increased TT was observed after fatiguing exercise for both sexes. Data
      indicate that the used fatigue protocol altered the latency and magnitude of
      reflex responses as well as TT in females and males. Based on the results of
      previous research and the outcome of this study, it might be that sex-specific
      effects of fatigue on reflex activity and mechanical stability of the knee depend
      on the kind of fatiguing exercise.

PMID- 25941066
TI  - Erratum to: Data sources for identifying low-income, uninsured populations:
      application to public health-National Breast and Cervical Cancer Early Detection
      Program.

PMID- 25941065
TI  - Association between plasma adiponectin levels and colorectal cancer risk in
      women.
AB  - BACKGROUND: Adiponectin, an adipocyte-secreted hormone, has insulin-sensitizing
      characteristics. It remains unclear whether adiponectin may influence colorectal
      cancer development. METHODS: To determine whether prediagnostic levels of
      adiponectin were associated with risk of incident colorectal cancer in the
      Women's Health Study, we conducted a nested case-control study of 275 colorectal
      cancer cases and 275 matched controls. Each case was matched to a control by age,
      ethnicity, fasting status at the time of blood collection, time of day when blood
      was drawn, and month of blood draw. Multivariable logistic regression with
      adjustment for colorectal cancer risk factors was used to estimate the odds ratio
      (OR) and 95 % confidence interval (CI) for risk of colorectal cancer incidence
      and mortality by adiponectin quartiles based on the control distribution.
      RESULTS: Median plasma adiponectin level was similar in cases versus controls
      (6.00 vs. 6.24 MUg/mL). In multivariable-adjusted logistic regression models,
      high plasma adiponectin levels were not significantly associated with risk of
      colorectal cancer [quartile 4 (Q4) vs. quartile 1 (Q1): OR (95 % CI) 0.86 (0.48
      1.56), p trend = 0.63]. CONCLUSIONS: These results suggest no appreciable
      association between plasma adiponectin and risk of colorectal cancer in women.
      Confirmation of these observations in larger studies is needed.

PMID- 25941069
TI  - Nomenclature for factors of the HLA system, update February 2015.

PMID- 25941070
TI  - Extensively Reversible Thermal Transformations of a Bistable, Fluorescence
      Switchable Molecular Solid: Entry into Functional Molecular Phase-Change
      Materials.
AB  - Functional phase-change materials (PCMs) are conspicuously absent among molecular
      materials in which the various attributes of inorganic solids have been realized.
      While organic PCMs are primarily limited to thermal storage systems, the
      amorphous-crystalline transformation of materials like Ge-Sb-Te find use in
      advanced applications such as information storage. Reversible amorphous
      crystalline transformations in molecular solids require a subtle balance between
      robust supramolecular assembly and flexible structural elements. We report novel
      diaminodicyanoquinodimethanes that achieve this transformation by interlinked
      helical assemblies coupled with conformationally flexible alkoxyalkyl chains.
      They exhibit highly reversible thermal transformations between bistable
      (crystalline/amorphous) forms, along with a prominent switching of the
      fluorescence emission energy and intensity. 

PMID- 25941071
TI  - Strong and Conductive Dry Carbon Nanotube Films by Microcombing.
AB  - In order to maximize the carbon nanotube (CNT) buckypaper properties, it is
      critical to improve their alignment and reduce their waviness. In this paper, a
      novel approach, microcombing, is reported to fabricate aligned CNT films with a
      uniform structure. High level of nanotube alignment and straightness was achieved
      using sharp surgical blades with microsized features at the blade edges to comb
      single layer of CNT sheet. These microcombs also reduced structural defects
      within the film and enhanced the nanotube packing density. Following the
      microcombing approach, the as-produced CNT films demonstrated a tensile strength
      of up to 3.2 GPa, Young's modulus of up to 172 GPa, and electrical conductivity
      of up to 1.8 * 10(5) S m(-1) , which are much superior to previously reported CNT
      films or buckypapers. More importantly, this novel technique requires less
      rigorous process control and can construct CNT films with reproducible
      properties. 

PMID- 25941072
TI  - Transudative chylothorax in a patient with liver cirrhosis: A rare association.
AB  - Chylothorax is an unusual type of pleural effusion which results from the
      accumulation of chyle in the pleural cavity. High triglyceride content and
      presence of chylomicrons in the chyle give this fluid a characteristic milky
      appearance. Chylothorax most commonly results from the obstruction of the
      thoracic duct by a malignant lesion or from its traumatic disruption. Liver
      cirrhosis is an uncommon and frequently underappreciated cause of chylothorax.
      Pleural effusion in chylothorax is typically described as a lymphocytic
      predominant, exudative type and it is exceedingly rare to encounter a
      transudative type of chylothorax. To date, very few cases of transudative
      chylothoraces have been described in the literature, most commonly in association
      with liver cirrhosis. Only a limited range of other clinical settings have been
      linked to transudative chylothorax and timely recognition of these associations
      can prevent unnecessary, expensive and sometimes invasive workup in this patient
      population. 

PMID- 25941073
TI  - Rho Kinase Pathway Alterations in the Brain and Leukocytes in Huntington's
      Disease.
AB  - Huntington's disease (HD) is a fatal neurodegenerative disease caused by an
      expanded polyglutamine tract in the huntingtin gene. Therapeutic approaches
      targeting mutant huntingtin (mtHtt) or its downstream toxic consequences are
      under development, including Rho kinase pathway inhibition. We investigated the
      messenger RNA (mRNA) expression of Rho kinase pathway genes, including RhoA (Ras
      homolog family member A), ROCK1 (Rho-associated kinase1), PRK2 (protein kinase C
      related protein kinase 2), Profilin1, cofilin1, MYPT1 (myosin phosphatase target
      subunit 1), and LIMK1 (LIM domain kinase 1) in HD human blood leukocytes,
      postmortem brain, and in R6/2 HD mouse brain tissue using qPCR. RhoA, ROCK1,
      PRK2, Profilin1, cofilin1, and MYPT1 were significantly increased in HD blood
      compared to controls. In frontal cortex of HD postmortem brain tissue, the
      expression of RhoA, ROCK1, PRK2, Profilin1, and MYPT1 were also significantly
      increased. In the brain from 4-week-old R6/2 mice, the expression of Rock1, Prk2,
      Cofilin1, and MYPT1 was significantly increased while RhoA, Rock1, Profilin1,
      Cofilin1, and Mypt1 were increased and Limk1 mRNA decreased in 13-week-old R6/2
      mice. Western blot analysis using human postmortem tissues for ROCK1 and
      Profilin1 demonstrated significantly increased protein levels, which correlated
      with the mRNA increases. Collectively, we have shown the panel of Rho kinase
      pathway genes to be highly altered in human HD blood, postmortem brain tissue,
      and in R6/2 mice. These studies confirm that HD upregulates the Rho kinase
      pathway and identifies mRNAs that could serve as peripheral markers in HD
      patients and translational markers in HD mouse models. 

PMID- 25941075
TI  - Distinct Hippocampal Expression Profiles of lncRNAs in Rats Exhibiting a PTSD
      like Syndrome.
AB  - Posttraumatic stress disorder (PTSD) refers to a series of clinical syndromes,
      including symptoms such as nightmares, hallucinations, severe anxiety, fear, and
      trauma related to the environment. These symptoms tend to occur after intense
      psychological trauma or physiological stress. Long non-coding RNAs (lncRNAs) have
      been shown to play key roles in various biological processes, although it is
      unknown whether they have important functions in PTSD. Here, we present the first
      study exploring the connection between lncRNAs and a PTSD-like syndrome in rats.
      We find distinct expression profiles of lncRNAs between PTSD-like syndrome rats
      and a control group, which provides information for further research on the
      differentiation of PTSD and transdifferentiation between the PTSD-like syndrome
      and the control group. This information will be helpful for finding new
      therapeutic targets for the treatment of PTSD. 

PMID- 25941074
TI  - The K(+)-Cl(-) Cotransporter KCC2 and Chloride Homeostasis: Potential Therapeutic
      Target in Acute Central Nervous System Injury.
AB  - The K(+)-Cl(-) cotransporter-2 (KCC2) is a well-known member of the
      electroneutral cation-chloride cotransporters with a restricted expression
      pattern to neurons. This transmembrane protein mediates the efflux of Cl(-) out
      of neurons and exerts a critical role in inhibitory gamma-aminobutyric acidergic
      (GABAergic) and glycinergic neurotransmission. Moreover, KCC2 participates in the
      regulation of various physiological processes of neurons, including cell
      migration, dendritic outgrowth, spine morphology, and dendritic synaptogenesis.
      It is important to note that down-regulation of KCC2 is associated with the
      pathogenesis of multiple neurological diseases, which is of particular relevance
      to acute central nervous system (CNS) injury. In this review, we aim to survey
      the pathogenic significance of KCC2 down-regulation under the condition of acute
      CNS injuries. We propose that further elucidation of the molecular mechanisms
      regarding KCC2 down-regulation after acute CNS injuries is necessary because of
      potential promising avenues for prevention and treatment of acute CNS injury. 

PMID- 25941076
TI  - Serum Levels of High-sensitivity C-Reactive Protein at Admission Are More
      Strongly Associated with Poststroke Depression in Acute Ischemic Stroke than
      Homocysteine Levels.
AB  - Inflammatory processes have fundamental roles in depression. The primary purpose
      of this study was to assess the serum levels of high-sensitivity C-reactive
      protein (Hs-CRP) and homocysteine (HCY) at admission to the presence of
      poststroke depression (PSD). From December 2012 to December 2013, first-ever
      acute ischemic stroke patients who were admitted to the hospital within the first
      24 h after stroke onset were consecutively recruited and followed up for 6
      months. Serum levels of Hs-CRP and HCY were tested at admission. Based on the
      symptoms, diagnoses of depression were made in accordance with DSM-IV criteria
      for depression at 6 months after stroke. Ninety-five patients (42.0%) showed
      depression (major + minor) at 6 months after admission, and in 69 patients
      (30.5%), this depression was classified as major. In the 69 patients with major
      depression, our results showed significantly higher Hs-CRP and HCY levels at
      admission than patients without major depression. After adjusting all other
      possible covariates, Hs-CRP and HCY still were independent predicators of PSD
      with adjusted OR of 1.332 (95% CI, 1.230-1.452; P < 0.001) and 1.138 (95% CI,
      1.072-1.274; P < 0.001), respectively. The area under the receiver operating
      characteristic curve values of Hs-CRP and HCY were 0.765 (95% CI, 0.701-0.9825)
      and 0.684 (95% CI, 0.610-0.757) for PSD, respectively. The prognostic accuracy of
      combined model (HCY and Hs-CRP) was higher compared to those biomarkers alone and
      other markers. Elevated serum levels of Hs-CRP and HCY at admission were found to
      be associated with depression 6 months after stroke, suggesting that these
      alterations might participate in the pathophysiology of depression symptoms in
      stroke patients.

PMID- 25941078
TI  - Characterisation of Lu AF33241: A novel, brain-penetrant, dual inhibitor of
      phosphodiesterase (PDE) 2A and PDE10A.
AB  - Here, we present a preliminary pharmacological characterisation of Lu AF33241, a
      novel, brain penetrant phosphodiesterase inhibitor of (PDE) 2A and 10A tool
      compound, in in vitro/in vivo assays indicative of PDE2A and/or PDE10A
      inhibition, and in vivo models/assays relevant to cognitive processing and
      antipsychotic-like activity. An assay was also included to investigate potential
      effects on motor activity. The in vitro selectivity of Lu AF33241 was determined
      against a panel of PDE enzymes. Lu AF33241 potently inhibited both full-length
      recombinant hPDE2A (Ki=4.2nM) and hPDE10A (Ki=42nM). The compound moderately
      inhibited both hPDE1C (Ki=1200nM), hPDE7B (Ki=890nM), and hPDE11A (Ki=1800nM). Lu
      AF33241 displayed a Ki above 5000nM against all other tested members of the PDE
      family. Albeit within a narrow dose range, Lu AF33241 attenuated sub-chronic
      phencyclidine-induced deficits in novel object recognition (3 and 10mg/kg),
      displayed antipsychotic-like activity in the conditioned avoidance response
      paradigm (10mg/kg), and did not induce catalepsy within a dose-range of 2-6mg/kg.
      Further catalepsy studies are needed to investigate a predictive safety window.
      Lu AF33241 represents a novel PDE2A/PDE10A inhibitor tool compound that may serve
      to further the understanding of the roles played by these enzymes in various CNS
      disorders. 

PMID- 25941077
TI  - Mutant Huntingtin and Elusive Defects in Oxidative Metabolism and Mitochondrial
      Calcium Handling.
AB  - Elongation of a polyglutamine (polyQ) stretch in huntingtin protein (Htt) is
      linked to Huntington's disease (HD) pathogenesis. The mutation in Htt correlates
      with neuronal dysfunction in the striatum and cerebral cortex and eventually
      leads to neuronal cell death. The exact mechanisms of the injurious effect of
      mutant Htt (mHtt) on neurons are not completely understood but might include
      aberrant gene transcription, defective autophagy, abnormal mitochondrial
      biogenesis, anomalous mitochondrial dynamics, and trafficking. In addition,
      deficiency in oxidative metabolism and defects in mitochondrial Ca(2+) handling
      are considered essential contributing factors to neuronal dysfunction in HD and,
      consequently, in HD pathogenesis. Since the discovery of the mutation in Htt, the
      questions whether mHtt affects oxidative metabolism and mitochondrial Ca(2+)
      handling and, if it does, what mechanisms could be involved were in focus of
      numerous investigations. However, despite significant research efforts, the
      detrimental effect of mHtt and the mechanisms by which mHtt might impair
      oxidative metabolism and mitochondrial Ca(2+) handling remain elusive. In this
      paper, I will briefly review studies aimed at clarifying the consequences of mHtt
      interaction with mitochondria and discuss experimental results supporting or
      arguing against the mHtt effects on oxidative metabolism and mitochondrial Ca(2+)
      handling.

PMID- 25941079
TI  - Investigations in foot shock stress of variable intensity in mice: Adaptation and
      role of angiotensin II.
AB  - The present study investigated the stress adaptation and role of angiotensin in
      response to repeated exposures of electric foot shocks of varying intensity. Mice
      were subjected to moderate (0.5mA) or severe (1.5mA) electric foot shocks for 1h
      for 5 days. Stress-induced behavioral changes were assessed by actophotometer,
      hole board, open field and social interaction tests. The serum corticosterone
      levels were measured as an index of HPA axis. Telmisartan (a selective AT1
      receptor blocker) was employed as a pharmacological tool. A single exposure of
      moderate and severe stress produced behavioral deficits and increased the
      corticosterone levels. The restoration of these alterations was observed in
      response to repeated exposures of moderate stress, while no adaptation was
      observed in severe foot shock stress. A single administration of telmisartan
      (5mg/kg) exacerbated the moderate stress-induced decrease in behavioral activity
      and increase in corticosterone levels on the first day of stress exposure,
      suggesting the anti-stress role of angiotensin. In contrast, telmisartan
      normalized severe stress-induced behavioral and biochemical alterations
      suggesting the stress inducing actions of angiotensin. Furthermore, treatment
      with telmisartan abolished the stress adaptive response following repeated
      exposures of moderate stress suggesting that angiotensin has an adaptive role. It
      is concluded that there is a differential adaptive response in foot shock stress
      depending upon the severity of stress. Angiotensin II may act as an anti-stress
      agent and helps to promote the adaptation during medium stress, whereas it may
      promote stress response during severe stress. 

PMID- 25941080
TI  - Mast cells, brain inflammation and autism.
AB  - Increasing evidence indicates that brain inflammation is involved in the
      pathogenesis of neuropsychiatric diseases. Mast cells (MCs) are located
      perivascularly close to neurons and microglia, primarily in the leptomeninges,
      thalamus, hypothalamus and especially the median eminence. Corticotropin
      releasing factor (CRF) is secreted from the hypothalamus under stress and,
      together with neurotensin (NT), can stimulate brain MCs to release inflammatory
      and neurotoxic mediators that disrupt the blood-brain barrier (BBB), stimulate
      microglia and cause focal inflammation. CRF and NT synergistically stimulate MCs
      and increase vascular permeability; these peptides can also induce each other's
      surface receptors on MCs leading to autocrine and paracrine effects. As a result,
      brain MCs may be involved in the pathogenesis of "brain fog," headaches, and
      autism spectrum disorders (ASDs), which worsen with stress. CRF and NT are
      significantly increased in serum of ASD children compared to normotypic controls
      further strengthening their role in the pathogenesis of autism. There are no
      clinically affective treatments for the core symptoms of ASDs, but pilot clinical
      trials using natural-antioxidant and anti-inflammatory molecules reported
      statistically significant benefit. 

PMID- 25941082
TI  - Mast cells and basophils in inflammatory and tumor angiogenesis and
      lymphangiogenesis.
AB  - Angiogenesis, namely, the growth of new blood vessels from pre-existing ones, is
      an essential process of embryonic development and post-natal growth. In adult
      life, it may occur in physiological conditions (menstrual cycle and wound
      healing), during inflammatory disorders (autoimmune diseases and allergic
      disorders) and in tumor growth. The angiogenic process requires a tightly
      regulated interaction among different cell types (e.g. endothelial cells and
      pericytes), the extracellular matrix, several specific growth factors (e.g.
      VEGFs, Angiopoietins), cytokines and chemokines. Lymphangiogenesis, namely, the
      growth of new lymphatic vessels, is an important process in tumor development, in
      the formation of metastasis and in several inflammatory and metabolic disorders.
      In addition to tumors, several effector cells of inflammation (mast cells,
      macrophages, basophils, eosinophils, neutrophils, etc.) are important sources of
      a wide spectrum of angiogenic and lymphangiogenic factors. Human mast cells
      produce a large array of angiogenic and lymphangiogenic molecules. Primary human
      mast cells and two mast cell lines constitutively express several isoforms of
      angiogenic (VEGF-A and VEGF-B) and the two lymphangiogenic factors (VEGF-C and
      VEGF-D). In addition, human mast cells express the VEGF receptor 1 (VEGFR-1) and
      2 (VEGFR-2), the co-receptors neuropilin-1 (NRP1) and -2 (NRP2) and the Tie1 and
      Tie2 receptors. Immunologically activated human basophils selectively produce
      VEGF-A and -B, but not VEGF-C and -D. They also release Angiopoietin1 that
      activates Tie2 on human mast cells. Collectively, these findings indicate that
      human mast cells and basophils might participate in the complex network involving
      inflammatory and tumor angiogenesis and lymphangiogenesis. 

PMID- 25941083
TI  - In the brain of mice, 3-iodothyronamine (T1AM) is converted into 3
      iodothyroacetic acid (TA1) and it is included within the signaling network
      connecting thyroid hormone metabolites with histamine.
AB  - 3-iodothyronamine (T1AM) and its oxidative product, 3-iodotyhyroacetic acid
      (TTA1A), are known to stimulate learning and induce hyperalgesia in mice. We
      investigated whether i)TA1 may be generated in vivo from T1AM, ii) T1AM shares
      with TA1 the ability to activate the histaminergic system. Tandem mass
      spectrometry was used to measure TA1 and T1AM levels in i) the brain of mice
      following intracerebroventricular (i.c.v.) injection of T1AM (11MUgkg(-1)), with
      or without pretreatment with clorgyline, (2.5mgkg(-1) i.p.), a monoamine oxidase
      inhibitor; ii) the medium of organotypic hippocampal slices exposed to T1AM
      (50nM). In addition, learning and pain threshold were evaluated by the light-dark
      box task and the hot plate test, respectively, in mice pre-treated subcutaneously
      with pyrilamine (10mgkg(-1)) or zolantidine (5mgkg(-1)), 20min before i.c.v.
      injection of T1AM (1.32 and 11MUgkg(-1)). T1AM-induced hyperalgesia (1.32 and
      11MUgkg(-1)) was also evaluated in histidine decarboxylase (HDC(-/-)) mice. T1AM
      and TA1 brain levels increased in parallel in mice injected with T1AM with the
      TA1/T1AM averaging 1.7%. Clorgyline pre-treatment reduced the increase in both
      T1AM and TA1. TA1 was the main T1AM metabolite detected in the hippocampal
      preparations. Pretreatment with pyrilamine or zolantidine prevented the pro
      learning effect of 1.32 and 4MUgkg(-1) T1AM while hyperalgesia was conserved at
      the dose of 11MUgkg(-1) T1AM. T1AM failed to induce hyperalgesia in HDC(-/-) mice
      at all the doses. In conclusion, TA1 generated from T1AM, but also T1AM, appears
      to act by modulating the histaminergic system. 

PMID- 25941084
TI  - Radiosynthesis and in vitro validation of (3)H-NS14492 as a novel high affinity
      alpha7 nicotinic receptor radioligand.
AB  - The neuronal alpha7 nicotinic acetylcholine receptor is a homo-pentameric ligand
      gated ion channel that is a promising drug target for cognitive deficits in
      Alzheimer's disease and schizophrenia. We have previously described (11)C-NS14492
      as a suitable agonist radioligand for in vivo positron emission tomography (PET)
      occupancy studies of the alpha7 nicotinic receptor in the pig brain. In order to
      investigate the utility of the same compound for in vitro studies, (3)H-NS14492
      was synthesized and its binding properties were characterized using in vitro
      autoradiography and homogenate binding assays in pig frontal cortex. (3)H-NS14492
      showed specific binding to alpha7 nicotinic receptors in autoradiography,
      revealing a dissociation constant (Kd) of 2.1+/-0.7nM and a maximum number of
      binding sites (Bmax) of 15.7+/-2.0fmol/mg tissue equivalent. Binding distribution
      was similar to that of another selective ligand (125)I-alpha-bungarotoxin ((125)I
      BTX) in autoradiography, and unlabeled NS14492 displaced (125)I-BTX with an
      inhibition constant (Ki) of 23nM. (3)H-NS14492 bound to alpha7 nicotinic
      receptors in homogenized pig frontal cortex with a Kd of 0.8+/-0.3nM and a Bmax
      of 30.2+/-11.6fmol/mg protein. This binding assay further revealed the Ki rank
      order for a number of alpha7 nicotinic receptor agonists, and positive allosteric
      modulators (PAMs). Further, we saw increased binding of (3)H-NS14492 to pig
      frontal cortex membranes when co-incubated with PNU-120596, a type II PAM. Taken
      together, these findings show that (3)H-NS14492 is a useful new in vitro
      radioligand for the pig alpha7 nicotinic receptor. 

PMID- 25941081
TI  - Signal transduction and chemotaxis in mast cells.
AB  - Mast cells play crucial roles in both innate and adaptive arms of the immune
      system. Along with basophils, mast cells are essential effector cells for
      allergic inflammation that causes asthma, allergic rhinitis, food allergy and
      atopic dermatitis. Mast cells are usually increased in inflammatory sites of
      allergy and, upon activation, release various chemical, lipid, peptide and
      protein mediators of allergic reactions. Since antigen/immunoglobulin E (IgE)
      mediated activation of these cells is a central event to trigger allergic
      reactions, innumerable studies have been conducted on how these cells are
      activated through cross-linking of the high-affinity IgE receptor (FcepsilonRI).
      Development of mature mast cells from their progenitor cells is under the
      influence of several growth factors, of which the stem cell factor (SCF) seems to
      be the most important. Therefore, how SCF induces mast cell development and
      activation via its receptor, KIT, has been studied extensively, including a cross
      talk between KIT and FcepsilonRI signaling pathways. Although our understanding
      of the signaling mechanisms of the FcepsilonRI and KIT pathways is far from
      complete, pharmaceutical applications of the knowledge about these pathways are
      underway. This review will focus on recent progresses in FcepsilonRI and KIT
      signaling and chemotaxis. 

PMID- 25941086
TI  - Integrating innate and adaptive immune cells: Mast cells as crossroads between
      regulatory and effector B and T cells.
AB  - A diversity of immune mechanisms have evolved to protect normal tissues from
      infection, but from immune damage too. Innate cells, as well as adaptive cells,
      are critical contributors to the correct development of the immune response and
      of tissue homeostasis. There is a dynamic "cross-talk" between the innate and
      adaptive immunomodulatory mechanisms for an integrated control of immune damage
      as well as the development of the immune response. Mast cells have shown a great
      plasticity, modifying their behavior at different stages of immune response
      through interaction with effector and regulatory populations of adaptive
      immunity. Understanding the interplays among T effectors, regulatory T cells, B
      cells and regulatory B cells with mast cells will be critical in the future to
      assist in the development of therapeutic strategies to enhance and synergize
      physiological immune-modulator and -suppressor elements in the innate and
      adaptive immune system. 

PMID- 25941085
TI  - Sphingosine-1-phosphate and other lipid mediators generated by mast cells as
      critical players in allergy and mast cell function.
AB  - Sphingosine-1-phosphate (S1P), platelet activating factor (PAF) and eicosanoids
      are bioactive lipid mediators abundantly produced by antigen-stimulated mast
      cells that exert their function mostly through specific cell surface receptors.
      Although it has long been recognized that some of these bioactive lipids are
      potent regulators of allergic diseases, their exact contributions to disease
      pathology have been obscured by the complexity of their mode of action and the
      regulation of their metabolism. Indeed, the effects of such lipids are usually
      mediated by multiple receptor subtypes that may differ in their signaling
      mechanisms and functions. In addition, their actions may be elicited by cell
      surface receptor-independent mechanisms. Furthermore, these lipids may be
      converted into metabolites that exhibit different functionalities, adding another
      layer of complexity to their overall biological responses. In some instances, a
      second wave of lipid mediator synthesis by both mast cell and non-mast cell
      sources may occur late during inflammation, bringing about additional roles in
      the altered environment. New evidence also suggests that bioactive lipids in the
      local environment can fine-tune mast cell maturation and phenotype, and thus
      their responsiveness. A better understanding of the subtleties of the
      spatiotemporal regulation of these lipid mediators, their receptors and functions
      may aid in the pursuit of pharmacological applications for allergy treatments. 

PMID- 25941088
TI  - Tracing differences between male and female breast cancer: both diseases own a
      different biology.
AB  - AIMS: Male breast cancer (MBC) is a rare and poorly characterized disease. In the
      present study we used a novel biomathematical model to further characterize MBC
      and to identify differences between male and female breast cancer (FBC). METHODS
      AND RESULTS: A total of 134 cases of MBC were stained immunohistochemically for
      13 key oncoproteins, and staining percentages were used in a mathematical model
      to identify dependency patterns between these proteins. The results were compared
      with a large group of FBC (n = 728). MBC and FBC clearly differed on the
      molecular level. In detail, the results suggest a different role for progesterone
      receptor (PR) compared to oestrogen receptor (ER) in MBC, while in FBC ER and PR
      show a similar pattern. In addition, Androgen receptor (AR) seems to be a more
      powerful effector in MBC. Grades 1 and 2 tumours were clearly separated from
      grade 3 tumours, and luminal types A and B tumours also showed a different
      pattern. CONCLUSIONS: Defined morphological and molecular phenotypes can be
      identified in MBC, but these seem to be the result of different molecular
      mechanisms and perhaps multiple genetic pathways, as characterized previously in
      FBC, emphasizing the rising concept that MBC and FBC should be regarded as
      different and unique diseases.

PMID- 25941087
TI  - Sulfation of ritodrine by the human cytosolic sulfotransferases (SULTs): Effects
      of SULT1A3 genetic polymorphism.
AB  - Previous studies have demonstrated the metabolism of ritodrine through sulfation.
      The current study was designed to identify the human SULTs that are capable of
      sulfating ritodrine and to investigate how genetic polymorphism of the major
      ritodrine-sulfating SULT, SULT1A3, may affect its sulfating activity. A
      systematic analysis revealed that of the 13 known human SULTs, SULT1A1, SULT1A3,
      and SULT1C4, were capable of mediating the sulfation of ritodrine, with SULT1A3
      displaying the strongest sulfating activity. Effects of genetic polymorphism on
      the sulfating activity of SULT1A3 were examined. By employing site-directed
      mutagenesis, 4 SULT1A3 allozymes were generated, expressed, and purified.
      Purified SULT1A3 allozymes were shown to exhibit differential sulfating activity
      toward ritodrine. Kinetic studies further demonstrated differential substrate
      affinity and catalytic efficiency among the SULT1A3 allozymes. Collectively,
      these results provided useful information concerning the differential metabolism
      of ritodrine through sulfation in different individuals. 

PMID- 25941089
TI  - A database of age-appropriate average MRI templates.
AB  - This article summarizes a life-span neurodevelopmental MRI database. The study of
      neurostructural development or neurofunctional development has been hampered by
      the lack of age-appropriate MRI reference volumes. This causes misspecification
      of segmented data, irregular registrations, and the absence of appropriate
      stereotaxic volumes. We have created the "Neurodevelopmental MRI Database" that
      provides age-specific reference data from 2 weeks through 89 years of age. The
      data are presented in fine-grained ages (e.g., 3 months intervals through 1 year;
      6 months intervals through 19.5 years; 5 year intervals from 20 through 89
      years). The base component of the database at each age is an age-specific average
      MRI template. The average MRI templates are accompanied by segmented partial
      volume estimates for segmenting priors, and a common stereotaxic atlas for
      infant, pediatric, and adult participants. The database is available online
      (http://jerlab.psych.sc.edu/NeurodevelopmentalMRIDatabase/).

PMID- 25941090
TI  - The Cambridge MRI database for animal models of Huntington disease.
AB  - We describe the Cambridge animal brain magnetic resonance imaging repository
      comprising 400 datasets to date from mouse models of Huntington disease. The data
      include raw images as well as segmented grey and white matter images with maps of
      cortical thickness. All images and phenotypic data for each subject are freely
      available without restriction from
      (http://www.dspace.cam.ac.uk/handle/1810/243361/). Software and anatomical
      population templates optimised for animal brain analysis with MRI are also
      available from this site. 

PMID- 25941091
TI  - Treatment of chronic plantar ulcer of the diabetic foot using an irremovable
      windowed fibreglass cast boot: prospective study of 177 patients.
AB  - The objective of this study was to evaluate the level of healing of chronic
      neuropathic plantar ulcers, using an irremovable windowed fibreglass cast boot,
      which is only opened after healing. A single-centre prospective study of a cohort
      of 177 diabetic patients with chronic neuropathic plantar ulcers was carried out.
      The duration of neuropathic plantar ulcers was 604 +/- 808 days, with a mean
      surface area of 4.6 +/- 6.5 cm(2) , a mean depth of 1.04 +/- 1.08 cm and a mean
      volume of 5.9 +/- 17.7 cm(3) . After a mean of 96 days of wearing a windowed
      fibreglass cast boot (min 9 days, max 664 days and median 68 days), the level of
      healing reached 83.6%, although 29 patients did not heal (16.4%). The compliance
      was at 95%. NPUs with bigger volumes (p = 0.037) and those located at the heels (
      p = 0.004) had significantly lower healing levels. Twenty-one patients had
      moderate peripheral arterial disease (12%), and 24 patients were ostectomized for
      underlying osteomyelitis (14%), before inclusion. Moderate peripheral arterial
      disease (p = 0.970) or operated osteomyelitis (p = 0.128) did not modify the
      level of healing significantly, which were of 81% and 70.8%, respectively.
      Complications include 12 ulcers due to the windowed fibreglass cast boot (i.e.
      7%) and two other ulcers being moderately infected, resulting in 2% of toe
      amputation, but there was no major amputation or phlebitis. The treatment of old
      and deep NPUs of the diabetic foot by wearing a windowed fibreglass cast boot
      without opening the boot prior to healing offers very high ulcer recovery levels.
      Windowed fibreglass cast boots were changed in only 26 cases (14.6%). In
      addition, compliance was excellent and of the order of 95%. Furthermore, moderate
      peripheral arterial disease or a recent ostectomy did not affect the efficacy of
      windowed fibreglass cast boot.

PMID- 25941092
TI  - N-Acetyl Cysteine Has Both Gastro-Protective and Anti-Inflammatory Effects in
      Experimental Rat Models: Its Gastro-Protective Effect Is Related to Its In Vivo
      and In Vitro Antioxidant Properties.
AB  - N-acetyl cysteine (NAC), a metabolite of sulphur-containing amino acid cysteine,
      is used as an antioxidant and a mucolytic agent. Therefore, we aimed to
      investigate anti-inflammatory and anti-ulcerative effects of NAC. We also
      intended to determine the relation between antiulcer effect of NAC and its
      antioxidant properties by biochemical evaluation. In this study a total of 15 rat
      groups (n = 6 per group) were used for inflammation and ulcer experiments. Anti
      inflammatory effects of NAC have been investigated on six rat groups with
      carrageenan (CAR)-induced paw oedema model. Antiulcer effects of NAC have been
      investigated on 24 h fasted nine rat groups with IND-induced ulcer model in the
      presence of positive (LAN, RAN, FAM, and OMEP), negative (untreated IND group)
      and intact control groups. In biochemical analyses of stomach tissues;
      glutathione S-transferase (GST), catalase (CAT), myeloperoxidase (MPO), and
      superoxide dismutase (SOD) enzyme activities and lipid peroxidation (LPO) and the
      glutathione (GSH) levels were determined. All doses of NAC exerted significant
      anti-inflammatory effect; even the effect of 900 mg/kg NAC was similar with that
      of DIC and IND. In gastric tissues NAC administration decreased the level of LPO
      and activity of CAT, which were increased by IND. Furthermore, NAC increased the
      GSH level and SOD and GST activities, which decreased in ulcerous stomach
      tissues. Only MPO activity increased in both IND and NAC groups when compared to
      healthy rat group. We determined that NAC has both anti-inflammatory and anti
      ulcerative effects.

PMID- 25941093
TI  - Bone Lesions, Lymphadenopathy, and Hepatic Granulomas in a Patient With
      Psoriasis.

PMID- 25941094
TI  - Erratum to: Mechanisms in the relation between GABRA2 and adolescent
      externalizing problems.

PMID- 25941095
TI  - Fully resolved NMR correlation spectroscopy.
AB  - A new correlation experiment cited as "push-G-SERF" is reported. In the resulting
      phased 2D spectrum, the chemical shift information is selected along the direct
      dimension, whereas scalar couplings involving a selected proton nucleus are
      edited in the indirect domain. The robustness of this pulse sequence is
      demonstrated on compounds with increasing structural and spectral complexity,
      using state-of-the-art spectrometers. It allows for full resolution of both
      dimensions of the spectrum, yielding a straightforward assignment and measurement
      of the coupling network around a given proton in the molecule. This experiment is
      intended for chemists who want to address efficiently the structural analysis of
      molecules with an overcrowded spectrum. 

PMID- 25941096
TI  - Reply to Letter to the Editor by Pujals et al.

PMID- 25941097
TI  - [New aspects of tumor pathology of the adrenal glands].
AB  - In daily routine pathology of the adrenal glands three tumor entities are
      important: adrenocortical tumors, adrenomedullary tumors and metastases. The
      differentiation of these three main tumor types can often be difficult
      structurally but immunostaining enables a definite diagnosis in nearly all cases.
      Adrenocortical tumors are positive for steroidogenic factor 1 and melan-A and
      always negative for chromogranin A whereas adrenomedullary tumors express
      chromogranin A but never keratin. A broad spectrum of antibodies is available for
      the identification of metastases and even the rare epithelioid angiosarcomas. For
      adrenocortical tumors, adenomas and carcinomas can be differentiated using three
      scoring systems and the Ki-67 index in adenomas should not exceed 3%. Using
      scoring systems and the Ki-67 index approximately 90% of cortical tumors can be
      differentiated into benign or malignant tumors. For pheochromocytomas two scoring
      systems are used for differentiating benign and malignant tumors but the results
      are less dependable.

PMID- 25941098
TI  - [Surprise in abrasion diagnostics].
AB  - Typical localizations of gynecological squamous cell carcinomas are the cervix,
      vulva and vagina and are therefore not uncommonly diagnosed in curettages. A
      differentiation from reactive hyperplastic alterations with a possible
      invasiveness in samples taken from the surface of the special type of well
      differentiated verrucous squamous cell carcinoma can be difficult. This pitfall
      of such a tumor is presented in the case described here with corresponding
      diagnostic difficulties. 

PMID- 25941099
TI  - [What is new in the pathology of pancreatic neuroendocrine tumors?].
AB  - The diagnostics of pancreatic neuroendocrine tumors (PanNEN) have changed in
      recent years especially concerning the World Health Organization (WHO)
      classification, TNM staging and grading. Furthermore, some new prognostic and
      predictive immunohistochemical markers have been introduced. Most progress,
      however, has been made in the molecular pathogenesis of these neoplasms. Using
      next generation sequencing techniques, the mammalian target of rapamycin (mTOR)
      pathway, hypoxia and epigenetic changes were identified as key players in
      tumorigenesis. In this article the most important developments of morphological
      as well as immunohistochemical diagnostics together with the molecular background
      of PanNEN are summarized. 

PMID- 25941101
TI  - Characterization of in utero valproic acid mouse model of autism by local field
      potential in the hippocampus and the olfactory bulb.
AB  - Valproic acid (VPA) mouse model of autism spectrum disorder (ASD) has been
      characterized mostly by impaired ultrasonic vocalization, poor sociability and
      increased repetitive self-grooming behavior. However, its neural signaling
      remained unknown. This study investigated the local field potentials (LFPs) in
      the dorsal hippocampal CA1 and the olfactory bulb while animals exploring a novel
      open field. VPA was administered at gestational day 13. The results demonstrated
      three core features of ASD in male offspring. However, there was no difference in
      Y-maze performance and locomotor activity. Analysis of hippocampal LFP power
      revealed significantly increased slow wave (1-4 Hz) and high gamma (80-140 Hz)
      oscillations and decreased theta (4-12 Hz) activity in VPA mice. In the olfactory
      bulb, VPA animals showed greater slow wave (1-4 Hz) and beta (25-40 Hz) activity
      and lower activity of low gamma (55-80 Hz) wave. Regression analysis revealed
      positive correlations between hippocampal theta power and locomotor speed for
      both control and VPA-exposed mice. There was no significant difference between
      groups for modulation index of theta (4-12 Hz) phase modulated gamma (30-200 Hz)
      amplitude. These findings characterized VPA mouse model with LFP oscillations
      that might provide better understanding of neural processing in ASD.

PMID- 25941102
TI  - Optimizing perioperative outcomes for older patients with rheumatoid arthritis
      undergoing arthroplasty: emphasis on medication management.
AB  - Patients with rheumatoid arthritis continue to undergo arthroplasty despite
      widespread use of potent disease-modifying drugs (DMARDs), including the biologic
      tumor necrosis-alpha inhibitors. In fact, over 80 % of RA patients are taking
      DMARDs or biologics at the time of arthroplasty. While many RA-specific factors
      including disease activity and disability may contribute to the increase in
      infection in RA patients undergoing arthroplasty, immunosuppressant medications
      may also play a role. As the age of patients with RA undergoing arthroplasty is
      rising, and the incidence of arthroplasty among the older population is
      increasing, optimal perioperative management of DMARDs and biologics in older
      patients with RA is an increasing challenge. Although evidence is sparse, most
      evidence supports withholding tumor necrosis-alpha inhibitors and other biologics
      prior to surgery based on the dosing interval, and continuing methotrexate and
      hydroxychloroquine through the perioperative period. There is no consensus
      regarding leflunomide, and rituximab risk does not appear related to the interval
      between infusion and surgery. This paper reviews arthroplasty outcomes including
      complications in patients with RA, and discusses the rationale for strategies for
      the optimal medication management of DMARDs and biologics in the perioperative
      period to minimize complications and improve outcomes.

PMID- 25941103
TI  - Head-to-Head Comparison of the Neuropsychiatric Effect of Dopamine Agonists in
      Parkinson's Disease: A Prospective, Cross-Sectional Study in Non-demented
      Patients.
AB  - INTRODUCTION: Dopaminergic agonists (DAs) are widely used to treat motor symptoms
      in Parkinson's disease (PD). The differential effect of DAs on neuropsychiatric
      symptoms of PD has not been accurately studied. MATERIALS AND METHODS: We
      performed a prospective cross-sectional study of 515 non-demented PD patients
      receiving treatment with pramipexole [n = 250, monotherapy or with levodopa (L
      dopa)], ropinirole (n = 150, monotherapy or with L-dopa), or L-dopa (n = 115,
      monotherapy); all formulations were immediate release. Neuropsychiatric
      disturbances were assessed through the Neuropsychiatric Inventory (NPI). Groups
      were matched in terms of age, education, sex, disease severity (Hoehn and Yahr),
      disease duration, executive function, total L-dopa daily equivalent dose, and
      concomitant psychotropic medications (antidepressants, anxiolytics and
      antipsychotic agents). RESULTS: Patients on pramipexole showed significantly
      lower total NPI scores than patients on ropinirole (17.2 +/- 11 vs. 20.9 +/- 13,
      p = 0.015). Regarding the spectrum of neuropsychiatric symptoms, pramipexole was
      associated with significantly lower apathy scores than the L-dopa group (1.01 +/-
      1.7 vs. 1.87 +/- 2.93, p = 0.02). The frequency of patients with clinically
      meaningful symptoms of apathy (NPI apathy scores >= 4) was significantly lower in
      the pramipexole group (11.2 %) than in the ropinirole (20.3 %) and L-dopa (23.8
      %) groups (chi (2) 12.49, p = 0.002). No other significant differences were found
      in NPI subscores between groups. CONCLUSIONS: This is the first head-to-head
      comparative study of the effect of DAs on neuropsychiatric disturbances in PD
      that has controlled the sample for the most important confounding factors. In
      comparable groups of patients, the use of pramipexole seems to be associated with
      a lower frequency and severity of apathetic symptoms.

PMID- 25941105
TI  - Capsule Commentary on Duan-Porter et al., Control Beliefs and Risk for Death,
      Stroke and Myocardial Infarction in Middle-aged and Older Adults: An
      Observational Study.

PMID- 25941106
TI  - Scimitar Syndrome.

PMID- 25941104
TI  - A Risk-Benefit Assessment of Dementia Medications: Systematic Review of the
      Evidence.
AB  - BACKGROUND: There is no cure for dementia, and no treatments exist to halt or
      reverse the course of the disease. Treatments are aimed at improving cognitive
      and functional outcomes. OBJECTIVE: Our objective was to review the basis of
      pharmacological treatments for dementia and to summarize the benefits and risks
      of dementia treatments. METHODS: We performed a systematic literature search of
      MEDLINE through November 2014, for English-language trials and observational
      studies on treatment of dementia and mild cognitive impairment. Additional
      references were identified by searching bibliographies of relevant publications.
      Whenever possible, pooled data from meta-analyses or systematic reviews were
      obtained. Studies were included for review if they were randomized trials or
      observational studies on dementia or mild cognitive impairment that evaluated
      efficacy outcomes or adverse outcomes associated with treatment. Studies were
      excluded if they evaluated non-FDA approved treatments, or if they evaluated
      treatment in disorders other than dementia and mild cognitive impairment.
      RESULTS: The literature search found 540 potentially relevant studies, of which
      257 were included in the systematic review. In pooled trial data, cholinesterase
      inhibitors (ChEIs) produce small improvements in cognitive, functional, and
      global benefits in patients with mild to moderate Alzheimer's and Lewy body
      dementia, but the clinical significance of these effects are unclear. There is no
      significant benefit seen for vascular dementia. The efficacy of ChEI treatment
      appears to wane over time, with minimal benefit seen after 1 year. There is no
      evidence for benefit for those with advanced disease or those aged over 85 years.
      Adverse effects are significantly increased with ChEIs, in a dose-dependent
      manner. A two- to fivefold increased risk for gastrointestinal, neurological, and
      cardiovascular side effects is related to cholinergic stimulation, the most
      serious being weight loss, debility, and syncope. Those aged over 85 years have
      double the risk of adverse events compared with younger patients. Memantine
      monotherapy may provide some cognitive benefit for patients with moderate to
      severe Alzheimer's and vascular dementia, but the benefit is small and may wane
      over the course of several months. Memantine exhibits no significant benefit in
      mild dementia or Lewy body dementia or as an add-on treatment with ChEIs.
      Memantine has a relatively favorable side-effect profile, at least under
      controlled trial conditions. CONCLUSIONS: ChEIs produce small, short-lived
      improvements in cognitive function in mild to moderate dementia, which may not
      translate into clinically meaningful effects. Marginal benefits are seen with
      severe disease, long-term treatment, and advanced age. Cholinergic side effects,
      including weight loss, debility, and syncope, are clinically significant and
      could be especially detrimental in the frail elderly population, in which the
      risks of treatment outweigh the benefits. Memantine monotherapy may have minimal
      benefits in moderate to severe dementia, balanced by minimal adverse effects.

PMID- 25941107
TI  - Comparison of Atrial Fibrillation Guidelines.

PMID- 25941108
TI  - Regio- and isoform-specific glucuronidation of psoralidin: evaluation of 3-o
      glucuronidation as a functional marker for UGT1A9.
AB  - In this study, we aimed to determine the glucuronidation potential of psoralidin
      in humans and to perform validation on use of psoralidin-3-O-glucuronidation as a
      functional marker for UGT1A9. Glucuronidation kinetics was determined using human
      liver microsomes (HLMs), human intestine microsomes (HIM), and expressed UDP
      glucuronosyltransferase (UGT) enzymes. The chemical structures of metabolites
      were determined by liquid chromatography-mass spectrometry and nuclear magnetic
      resonance spectroscopy analyses. Validation of psoralidin-3-O-glucuronidation as
      a UGT1A9 marker was performed using combined approaches including reaction
      phenotyping, chemical inhibition, activity correlation analysis, and
      determination of relative activity factor (RAF). HLM and UGT1A9 generated two
      monoglucuronides (9-O-glucuronide and 3-O-glucuronide) from psoralidin, whereas
      HIM, UGT1A1, UGT1A7, and UGT1A8 generated one only (9-O-glucuronide). Formation
      of 3-O-glucuronide in HLM was markedly inhibited by the UGT1A9-selective
      inhibitors magnolol and niflumic acid. Further, psoralidin-3-O-glucuronidation
      was strongly correlated with propofol-glucuronidation in a group of nine
      individual HLMs (r = 0.978, p < 0.001). Strong correlation was also observed
      between psoralidin-3-O-glucuronidation and the UGT1A9 protein levels measured by
      Western blotting (r = 0.944, p < 0.001). Moreover, UGT1A9 was responsible for
      99.6% of psoralidin-3-O-glucuronidation in HLM based on the RAF approach. In
      conclusion, psoralidin was subjected to efficient glucuronidation, generating one
      or two monoglucuronides depending on UGT isozymes. Also, psoralidin-3-O
      glucuronidation was an excellent in vitro marker for UGT1A9.

PMID- 25941109
TI  - Severe Vitamin D Deficiency May be an Additional Cofactor for the Occurrence of
      Alcoholic Steatohepatitis.
AB  - BACKGROUND: Among its pleiotropic effects, vitamin D may protect the liver from
      fibrosis and/or inflammation. However, the impact of vitamin D on liver pathology
      in hepatitis C remains unclear, and very few studies including alcoholic patients
      with liver pathologies have been performed. Here we compared the levels of 25-OH
      vitamin D in the blood of alcoholic patients with the occurrence of alcoholic
      steatohepatitis (ASH) or bridging fibrosis. METHODS: One hundred and one
      alcoholic patients were included. All the patients received a liver biopsy, and
      the levels of 25-OH vitamin D were evaluated with the Liaison 25-OH vitamin D
      assay. Logistic regression analyses were performed to obtain predictive factors
      of liver histology. RESULTS: Among alcoholic patients, 40.6% presented ASH and
      39.6% presented bridging fibrosis. A severe deficiency in 25-OH vitamin D (<10
      ng/ml) was seen in 60.4% of patients. This deficiency was frequent in patients
      with ASH (85.4%) and in those with bridging fibrosis (80%) but was independently
      associated only with ASH (odds ratio = 8.46 [95% confidence interval 2.05 to
      34.89], p = 0.003). CONCLUSIONS: In alcoholic patients, a severe deficiency in 25
      OH vitamin D was independently associated with the occurrence of ASH.

PMID- 25941110
TI  - Acute Calcific Tendinitis of the Longus Colli Muscle.

PMID- 25941111
TI  - Molecular Pathways: Targeting the Cyclin D-CDK4/6 Axis for Cancer Treatment.
AB  - Cancer cells bypass normal controls over mitotic cell-cycle progression to
      achieve a deregulated state of proliferation. The retinoblastoma tumor suppressor
      protein (pRb) governs a key cell-cycle checkpoint that normally prevents G1-phase
      cells from entering S-phase in the absence of appropriate mitogenic signals.
      Cancer cells frequently overcome pRb-dependent growth suppression via
      constitutive phosphorylation and inactivation of pRb function by cyclin-dependent
      kinase (CDK) 4 or CDK6 partnered with D-type cyclins. Three selective CDK4/6
      inhibitors, palbociclib (Ibrance; Pfizer), ribociclib (Novartis), and abemaciclib
      (Lilly), are in various stages of development in a variety of pRb-positive tumor
      types, including breast cancer, melanoma, liposarcoma, and non-small cell lung
      cancer. The emerging, positive clinical data obtained to date finally validate
      the two decades-old hypothesis that the cyclin D-CDK4/6 pathway is a rational
      target for cancer therapy.

PMID- 25941112
TI  - Polymorphisms of IL-10 affect the severity and prognosis of myelodysplastic
      syndrome.
AB  - Polymorphisms of the interleukin-10 (IL-10) gene, which alter the production of
      IL-10, have been implicated in many cancers. We investigated the association
      between gene polymorphisms of the promoter region of IL-10 (-1082 G/A, IL-10-819
      C/T, and -592 C/A) and the risk to develop myelodysplastic syndrome (MDS) and
      clinical features of MDS. Genomic DNA was extracted from 119 patients with MDS or
      chronic myelomonocytic leukemia and 202 healthy controls. Genotypes were
      determined by PCR-restriction fragment length polymorphism. There were no
      statistically significant differences in the genotype, allele, and haplotype
      frequencies of IL-10 -1082 G/A, IL-10-819 C/T, and -592 C/A between the patients
      with MDS and the control group. However, the IL-10 -592 CC genotype group (IL-10
      high producer type) was associated with lower hemoglobin level (7.85 +/- 2.02
      g/dL vs. 9.37 +/- 2.25 g/dL, P = 0.027) and poorer prognosis as compared to the
      IL-10 -592 non-CC genotype group (median survival time 50.2 m vs. not reached, p
      = 0.026). In addition, the IL-10 high producer haplotype group (GCC/ACC or
      ACC/ACC) was also associated with lower hemoglobin level and shorter survival
      time. Our findings indicate that IL-10 gene polymorphisms may not contribute to
      susceptibility to MDS, but they may be associated with the severity and prognosis
      of MDS.

PMID- 25941113
TI  - Bimatoprost in periorbital vitiligo: a ray of hope or dilemma.

PMID- 25941114
TI  - Expression of toll-like receptors in HPV-positive and HPV-negative oropharyngeal
      squamous cell carcinoma--an in vivo and in vitro study.
AB  - The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has increased over
      the past decades in many western countries. This trend is mainly attributed to
      the human papillomavirus (HPV). Cancer-related actions of immunological defense
      systems are being intensively researched. Human toll-like receptors (TLRs) are a
      family of pattern recognition receptors that participate in the immunological
      defense against pathogens, but their actions are also linked to cancer. The
      expression of TLRs in cervical epithelium alters both during the clearance of HPV
      infection and the HPV-induced neoplasia, but the expression of TLRs has not been
      studied in OPSCC. Thirty-five paraffin-embedded, formalin-fixed, squamous cell
      carcinoma tissue specimens were analyzed for TLRs 2, 3, 4, 5, 7, and 9 and HPV
      and p16 statuses. The TLR 9 expression was lower in HPV-positive tumors compared
      with HPV-negative tumors. TLR 7 was expressed in all cancer specimens, but
      elevated expression was evident in HPV and/or p16-positive tumors. The majority
      of p16-positive tumors did not express TLR 5, whereas its expression was stronger
      in p16-negative tumors. The results of in vitro analysis of five human OPSCC cell
      lines and one human oral tongue squamous cell carcinoma cell line agree with the
      in vivo trends: low levels of TLR 5 and high levels of TLR 7 in p16-positive
      OPSCC. Overall, TLR 7 and 9 expression patterns are demonstrated here to relate
      to the HPV status in vivo and TLR 5 and 7 expression patterns to the p16 status
      in vivo and in vitro.

PMID- 25941116
TI  - Preparation of adamantyl derivatives of 1,4-; 1,6- and 1,7-dihydroxynaphthalenes
      and assignment of their NMR data.
AB  - Adamantylation of dihydroxynaphthalenes with the hydroxyl groups on the same or
      different rings leads to compounds that are convenient starting materials in
      target-oriented organic synthesis. Here, we report the (1)H and (13)C NMR
      assignments of eight 1-adamantyl substituted derivatives of 1,4-; 1,6- and 1,7
      dihydroxynaphthalenes. The data acquired and peculiarities of their molecular
      structure are useful for extrapolation for prompt characterization of compounds
      containing adamantane, dihydroxynaphthalenes or naphthoquinone units.

PMID- 25941115
TI  - MiR-371-373 cluster acts as a tumor-suppressor-miR and promotes cell cycle arrest
      in unrestricted somatic stem cells.
AB  - Recent advances in small RNA research have implicated microRNAs (miRNAs) as
      important regulators of proliferation and development. The miR-371-373 cluster is
      prominently expressed in human embryonic stem cells (ESCs) and rapidly decreases
      after cell differentiation. MiR-371-373 cluster was investigated as one of the
      key factors of stem cell maintenance and pluripotency in unrestricted somatic
      stem cells (USSCs) using a lentivirus system. Gene expression showed a dual
      effect on proliferation, which revealed a transient cell cycle progression and
      consequent repression in pluripotency factors and cell cycle genes. Cell
      proliferation analysis with CFU, MTT, and DNA content assays further confirmed
      the dual effect of cluster after prolonged exposure. Analyzing the course of
      action, it seems that miR-371-373 cluster acts as an onco/tumor suppressor-miR.
      MiR371-373 cluster acts by modulating the function of these factors and limiting
      the excessive cell cycle propagation upon oncogenic stimuli to protect cells from
      replicative stress, but also activate CDK inhibitors and transcriptional
      repressors of the retinoblastoma family to cause cell cycle arrest. In contrast
      to the previous studies, we believe that miR-371-373 cluster functions as a self
      renewal miRNA to induce and maintain the pluripotent state but also to
      potentially inhibit dysregulated proliferation through cell cycle arrest. It
      seems that miR-371-373 cluster presents with a dual effect in this cellular
      context which may possess different actions in various cells. This not only
      expands the basic knowledge of the cluster but may offer a great chance for
      therapeutic interventions.

PMID- 25941118
TI  - The national essential anaesthesia drugs list.

PMID- 25941117
TI  - Breast cancer cell line MCF7 escapes from G1/S arrest induced by proteasome
      inhibition through a GSK-3beta dependent mechanism.
AB  - Targeting the ubiquitin proteasome pathway has emerged as a rational approach in
      the treatment of human cancers. Autophagy has been described as a cytoprotective
      mechanism to increase tumor cell survival under stress conditions. Here, we have
      focused on the role of proteasome inhibition in cell cycle progression and the
      role of autophagy in the proliferation recovery. The study was performed in the
      breast cancer cell line MCF7 compared to the normal mammary cell line MCF10A. We
      found that the proteasome inhibitor MG132 induced G1/S arrest in MCF10A, but G2/M
      arrest in MCF7 cells. The effect of MG132 on MCF7 was reproduced on MCF10A cells
      in the presence of the glycogen synthase kinase 3beta (GSK-3beta) inhibitor VII.
      Similarly, MCF7 cells overexpressing constitutively active GSK-3beta behaved like
      MCF10A cells. On the other hand, MCF10A cells remained arrested after MG132
      removal while MCF7 recovered the proliferative capacity. Importantly, this
      recovery was abolished in the presence of the autophagy inhibitor 3-methyladenine
      (3-MA). Thus, our results support the relevance of GSK-3beta and autophagy as two
      targets for controlling cell cycle progression and proliferative capacity in
      MCF7, highlighting the co-treatment of breast cancer cells with 3-MA to synergize
      the effect of the proteasome inhibition. 

PMID- 25941119
TI  - Patterns of time use among low-income urban minority adolescents and associations
      with academic outcomes and problem behaviors.
AB  - Time budgets represent key opportunities for developmental support and contribute
      to an understanding of achievement gaps and adjustment across populations of
      youth. This study assessed the connection between out-of-school time use patterns
      and academic performance outcomes, academic motivations and goals, and problem
      behaviors for 504 low-income urban African American and Latino adolescents (54%
      female; M = 16.6 years). Time use patterns were measured across eight activity
      types using cluster analysis. Four groups of adolescents were identified, based
      on their different profiles of time use: (1) Academic: those with most time in
      academic activities; (2) Social: those with most time in social activities; (3)
      Maintenance/work: those with most time in maintenance and work activities; and
      (4) TV/computer: those with most time in TV or computer activities. Time use
      patterns were meaningfully associated with variation in outcomes in this
      population. Adolescents in the Academic cluster had the highest levels of
      adjustment across all domains; adolescents in the Social cluster had the lowest
      academic performance and highest problem behaviors; and adolescents in the
      TV/computer cluster had the lowest levels of intrinsic motivation. Females were
      more likely to be in the Academic cluster, and less likely to be in the other
      three clusters compared to males. No differences by race or gender were found in
      assessing the relationship between time use and outcomes. The study's results
      indicate that time use patterns are meaningfully associated with within-group
      variation in adjustment for low-income minority adolescents, and that shared
      contexts may shape time use more than individual differences in race/ethnicity
      for this population.

PMID- 25941120
TI  - The Dopamine D2 Receptor Polymorphism (DRD2 TaqIA) Interacts with Maternal
      Parenting in Predicting Early Adolescent Depressive Symptoms: Evidence of
      Differential Susceptibility and Age Differences.
AB  - Most gene-environment interaction research on depression has largely focused on
      negative environment and to a lesser extent on positive environment. Moreover, to
      date few studies have directly examined G * E at different periods in
      development, particularly during early adolescence. The present study addressed
      these issues by examining the concurrent and prospective longitudinal effects of
      maternal parenting, DRD2 TaqIA polymorphism, and their interaction on adolescent
      depressive symptoms in a sample of 1026 Chinese adolescents (Mage = 11.33 +/-
      0.47 years at T1, 50.3% girls) in a three-wave longitudinal study from age 11 to
      13. Results indicated that maternal positive and negative parenting significantly
      concurrently predicted adolescent depressive symptoms at all three waves, whereas
      TaqIA polymorphism had no main effect on depressive symptoms. TaqIA polymorphism
      interacted with negative parenting in predicting concurrent depressive symptoms
      at age 11 and 12. A1 carriers were more susceptible to negative parenting
      compared to A2A2 homozygotes, such that adolescents carrying A1 alleles
      experiencing high negative parenting reported more depressive symptoms but fared
      better when experiencing low negative parenting. However, the interaction became
      nonsignificant at age 13, indicating the interaction of TaqIA polymorphism and
      maternal parenting may vary with development. Also, there was no G * E effect on
      longitudinal change in depression. The findings provided evidence in support of
      the differential susceptibility hypothesis and shed light on the potential for
      dynamic change in gene-environment interactions over development.

PMID- 25941122
TI  - Otoacoustic emission testing in Ghanaian children with sickle-cell disease.
AB  - OBJECTIVE: To evaluate hearing loss in children as a complication of sickle-cell
      disease. METHODS: In Kumasi, Ghana, 35 children with SCD aged 6 months to 10
      years underwent transient-evoked otoacoustic emissions testing (TEOAE) to
      investigate the function of the inner ear. Healthy Ghanaian children recruited in
      school and kindergarten served as controls. RESULTS: One of 35 children with SCD
      and 13 of 115 control children failed the otoacoustic emissions testing. This
      difference between the control group and the children with SCD was not
      statistically significant. CONCLUSION: Early hearing impairment does not
      regularly occur in sickle-cell disease, and in children, it is not a likely cause
      of delayed or impaired language development.

PMID- 25941121
TI  - Combined administration of levetiracetam and valproic acid attenuates age-related
      hyperactivity of CA3 place cells, reduces place field area, and increases spatial
      information content in aged rat hippocampus.
AB  - Learning and memory deficits associated with age-related mild cognitive
      impairment have long been attributed to impaired processing within the
      hippocampus. Hyperactivity within the hippocampal CA3 region that is associated
      with aging is mediated in part by a loss of functional inhibitory interneurons
      and thought to underlie impaired performance in spatial memory tasks, including
      the abnormal tendency in aged animals to pattern complete spatial
      representations. Here, we asked whether the spatial firing patterns of
      simultaneously recorded CA3 and CA1 neurons in young and aged rats could be
      manipulated pharmacologically to selectively reduce CA3 hyperactivity and thus,
      according to hypothesis, the associated abnormality in spatial representations.
      We used chronically implanted high-density tetrodes to record the spatial firing
      properties of CA3 and CA1 units during animal exploration for food in familiar
      and novel environments. Aged CA3 place cells have higher firing rates, larger
      place fields, less spatial information content, and respond less to a change from
      a familiar to a novel environment than young CA3 cells. We also find that the
      combination of levetiracetam (LEV) + valproic acid (VPA), previously shown to act
      as a cognitive enhancer in tests of spatial memory, attenuate CA3 place cell
      firing rates, reduce place field area, and increase spatial information content
      in aged but not young adult rats. This is consistent with drug enhancing the
      specificity of neuronal firing with respect to spatial location. Contrary to
      expectation, however, LEV + VPA reduces place cell discrimination between novel
      and familiar environments, i.e., spatial correlations increase, independent of
      age even though drug enhances performance in cognitive tasks. The results
      demonstrate that spatial information content, or the number of bits of
      information encoded per action potential, may be the key correlate for
      enhancement of spatial memory by LEV + VPA.

PMID- 25941123
TI  - Use of a vessel loop to ensure tunnel patency during LeFort colpocleisis.
AB  - INTRODUCTION: The objective was to describe a novel method for maintaining
      bilateral channel patency for potential uterine drainage during LeFort
      colpocleisis. METHODS: This video presents a novel approach for ensuring
      bilateral channel patency during colpocleisis. An 88-year-old gravida 2 para 2
      with stage 4 uterovaginal prolapse presented for definitive surgical management.
      She was no longer sexually active. After counseling on various treatment options,
      she elected to proceed with a LeFort colpocleisis. During the procedure, the
      vaginal epithelium is dissected off the underlying tissue with sharp dissection
      after infiltration with local anesthetic. After the epithelium is removed
      anteriorly and posteriorly, a blue vessel loop is placed across the cervix and
      within the lateral channels as they are created with a series of figure of eight
      stitches. Care is taken to suture around and not through the vessel loop. This is
      done on both sides. The anterior and posterior dissected surfaces of the vagina
      are then reapproximated to involute the vagina until the distal epithelial edges
      can be brought together. Once the vaginal epithelial edges are sewn, the vessel
      loop is easily pulled through, ensuring channel patency. CONCLUSIONS: The vessel
      loop technique demonstrated in this video allows the surgeon to ensure that the
      bilateral channels remain patent throughout the procedure.

PMID- 25941124
TI  - Repair of a recurrent rectovaginal fistula with a biological graft.
AB  - This case involves a patient with the congenital absence of the lower third of
      the vagina. While undergoing surgical restoration of the vagina, she sustained a
      laceration, which ultimately led to the development of a rectovaginal fistula.
      After two unsuccessful attempts at repair, the recommendation was for a diverting
      colostomy with another attempted repair, and she presented to our clinic to
      discuss other possible surgical options. The patient underwent repair of the
      fistula using a porcine-derived small intestinal submucosal extracellular matrix
      graft, which resulted in the repair of the rectovaginal fistula without
      recurrence at 18 months' follow-up.

PMID- 25941125
TI  - Does anesthetic method influence vaginal bulge symptoms and patient satisfaction
      after vaginal wall repair surgery?
AB  - INTRODUCTION AND HYPOTHESIS: Surgery for pelvic organ prolapse (POP) under local
      anesthesia has been advocated for several reasons such as lower costs and
      application in multimorbid patients. The aim of this study was to investigate how
      the anesthetic method influences the rate of recurrent prolapse and patient
      satisfaction with POP surgery. METHODS: In this retrospective study 4,936 women
      operated for single-compartment prolapse between 2006 and 2011 were included from
      the Swedish National Register for Gynecological Surgery. The feeling of vaginal
      bulge 1 year after surgery indicated presence of recurrent prolapse. Multivariate
      logistic regression analyses were used to identify independent factors affecting
      the outcomes, presented as adjusted odds ratios (aOR) with 95 % confidence
      interval (CI). RESULTS: After surgery for single-compartment prolapse patients
      with cystocele were at a higher risk of feeling a vaginal bulge than patients
      with rectocele (1.62, CI 1.28-2.06). Applied anesthesia was no independent
      predictor of bulge symptoms in the cystocele/rectocele population. In the
      cystocele group local anesthesia compared with general or regional anesthesia
      implied an increased risk of vaginal bulge symptoms (1.32, CI 1.03-1.68) as well
      as POP-Q-stage III-IV (1.30, CI 1.09-1.55), and a higher BMI class (1.22, CI 1.03
      1.46), while a higher age class decreased the risk (0.79, CI 0.70-0.89). Choice
      of anesthesia had no impact on bulge symptoms in the rectocele group and no
      influence on patient satisfaction in any of the groups. CONCLUSION: Patients
      operated for cystocele under local anesthesia were at a higher risk of
      experiencing vaginal bulge symptoms 1 year after surgery compared with general or
      regional anesthesia.

PMID- 25941126
TI  - PCR-based assay for the mitochondrial cox1 specific amplification of Eucoleus
      bohmi.
AB  - Eucoleus bohmi (syn. Capillaria boehmi) is a trichuroid nematode affecting the
      epithelium of the nasal turbinates, frontal and paranasal sinuses of wild and
      domestic canids. Knowledge of the geographic distribution of nasal eucoleosis is
      fragmentary, despite the infection has been described from Europe and North
      America. Moreover, gaps exist in information available on the importance of the
      disease in canine clinical practice. The lack of knowledge on E. bohmi is likely
      due to limitations inherent to diagnostic methodologies. The aim of the present
      work was to assess a PCR-based assay instrumental to the amplification of a
      species-specific region of the mitochondrial DNA (mtDNA) gene encoding for the
      subunit 1 (cox1) gene of E. bohmi. Adult worms of E. bohmi from red foxes and
      dogs from Norway, Serbia and Italy and individual fecal samples from naturally
      infected dogs from Italy were included in the study. Stool samples from dogs
      negative for E. bohmi, but positive for other common parasites in both single and
      mixed infections, and adult stages of common dog parasites, were used to assess
      the specificity of this genetic assay. Using the panel of faecal samples, the
      assay showed a sensitivity of 85.14% and a specificity of 100%. 

PMID- 25941127
TI  - Identifying the last bloodmeal of questing sheep tick nymphs (Ixodes ricinus L.)
      using high resolution melting analysis.
AB  - The sheep tick, Ixodes ricinus L., is an important hematophagous vector of
      zoonotic disease of both veterinary and public health importance in Europe. Risk
      models for tick-borne diseases can be improved by identifying the main hosts of
      this species in any given area. However, this generalist tick stays on a host for
      only a few days a year over its life cycle, making the study of its feeding
      ecology difficult. In contrast, ticks can easily be collected from vegetation
      when they are questing. Molecular methods have proved to be a reliable
      alternative to field observation, but most current methods have low sensitivity
      and/or low identification success (i.e. hosts are only identified to taxonomic
      levels higher than species). In this study we use Real-time PCR coupled with High
      Resolution Melting Analysis (HRMA) to identify the source of the last bloodmeal
      in questing tick nymphs. Twenty of the most important tick hosts were grouped
      taxonomically and six group-specific primer sets, targeting short mitochondrial
      DNA regions, were designed de novo. Firstly, we show that these primers
      successfully amplify target host DNA (from host tissue or engorged ticks), and
      that HRMA can be used to reliably identify hosts to species (or genera in the
      case of Sorex and Apodemus). Secondly, the new protocol was tested on field
      collected questing nymphs. Bloodmeal source was identified in 65.4% of 52
      individuals. In 83.3% of these, the host was identified to species or genera
      using HRMA alone. Moreover, the primer sets designed here can unequivocally
      identify mixed bloodmeals. The combination of sensitivity and identification
      success together with the closed-tube and single step approach that minimizes
      contamination, make Real-time HRMA a good alternative to current methods for
      bloodmeal identification. 

PMID- 25941128
TI  - [Effectiveness of pidotimod in combination with bacterial lysates in the
      treatment of the pfapa (periodic fever, aphthous stomatitis, pharyngitis, and
      cervical adenitis) syndrome].
AB  - AIM: PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and cervical
      adenitis) syndrome is the most common autoinflammatory syndrome in pediatrics,
      accepted as an hyperimmune condition. Pidotimod is a molecule with
      immunomodulatory activity on both innate and adaptive immune responses; it also
      has the capacity to modulate the function of the respiratory epithelial cells
      through the activation of a NK-KB pathway which would involve the host-virus
      interaction. Moreover, the proven beneficial effect of Pidotimod in enhancing the
      immune response during vaccination, and its benefits in the prevention of
      respiratory tract infections, should be noted. METHODS: A joint combination of
      Pidotimod and bacterial lysates was used to treat 37 children with a clinical
      diagnosis of PFAPA; within the end of the first year of therapy, the healing rate
      of PFAPA symptoms was 67.5% (25 children), with a 10.8% (4 cases) still in
      complete remission within the end of the second year of follow-up. RESULTS: It is
      important to highlight that 29 children (78.3%) had benefitted from this therapy,
      in terms of healing, with a marked decrease in the incidence of fever from a
      total of 360 to 106 episodes, and episodes of periodic fever occurring almost 4
      times less frequently. The use of Pidotimod determined a significant reduction of
      surgical tonsillectomy's treatment. CONCLUSION: This approach had a strong impact
      on the children's quality of life; a significant decrement in the use of
      antipyretic drugs, as well as a lower rate of antibiotic prescription, were also
      noted. It also had a dramatic impact on families' lives, because the treatment
      lowers the number of absences of family members from work or school/kindergarten.

PMID- 25941129
TI  - Evaluation of risk factors for retinopathy in preterm infant: a case-control
      study in a referral hospital in Iran.
AB  - AIM: Aim of the study was to detect possible risk factors for retinopathy of
      prematurity (ROP), as a leading cause of treatable childhood blindness, among
      premature neonates. METHODS: In this retrospective study, 60 premature neonates
      with ROP and 60 premature infants without ROP were entered and compared.
      Variables such as gestational age, birth weight, oxygen therapy, phototherapy,
      and so on were gathered and compared between the two groups. RESULTS: Significant
      statistical differences were seen regarding gestational age (29.3+/-3.1 weeks in
      the ROP group vs. 31.9+/-2.2 in control group) and first-minute apgar score
      (6.55+/-1.7 in the ROP group vs. 7.06+/-2.3 in the control group). Regarding
      comparisons made in terms of therapeutic interventions made, only oxygen therapy
      and phototherapy showed significant differences between the two groups which were
      higher in the ROP group. CONCLUSION: Gestational age (lower in the ROP group),
      first-minute Apgar score (lower mean score in the ROP group), birth weight,
      phototherapy, and oxygen therapy were factors discovered to affect the occurrence
      of ROP among premature infants. Higher birth weight and more advanced gestational
      age were protective factors for ROP. Oxygen therapy and multiple birth are ROP
      risk factors and these can be used for prediction of ROP occurrence.

PMID- 25941130
TI  - Efficacy and safety of a medical device in reducing nasal obstruction in allergic
      children.
AB  - AIM: Despite the availability of a number of pharmacological options, relief of
      allergic rhinitis (AR) symptoms, especially nasal obstruction, is often limited
      and local and systemic adverse reactions are not infrequent. The main aim of the
      present pilot study was to provide subjective and objective evidence of the
      clinical efficacy in reducing symptoms and safety of a medical device-Grip stop
      DMG (lactoferrin, carboximetil beta-glucan, D-panthenol,
      dipotassiumglycyrrhizinate) in children affected by allergic rhinitis. METHODS: A
      prospective study with a pre- and post-design has been performed consecutively
      enrolling 50 pediatric both genders patients affected by persistent AR. Patients
      received 2 puffs into each nostril twice a day over the course of 4 weeks. The
      severity of AR symptoms was assessed subjectively as measured by a 0 to 5 Visual
      Analog Scale, and objectively through active anterior rhinomanometry (AAR) and by
      means of the evaluation of mucociliary transport time (MCTt). Differences in
      symptoms scores measured before and after the treatment were compared using
      Paired-Sample Wilcoxon Signed Rank Test. Proportion of participants with adverse
      effects attributed to the treatment was computed. The relationship between the
      subjective score and the AAR and MCT measurements was also assessed. RESULTS: All
      considered symptoms, including nasal congestion, significantly improved after
      treatment (P<0.001), while only 1 patient suffered from moderate adverse effects.
      CONCLUSION: Results confirm efficacy and safety of this device used in the
      pediatric population. As previously reported in the scientific literature, also
      in our study, patient's perception of nasal symptoms corresponded with objective
      testing.

PMID- 25941131
TI  - DNA damage in children with scoliosis following X-ray exposure.
AB  - AIM: It has been suggested that cancer incidence is high in subjects with
      scoliosis who are relatively more often exposed to X-ray for diagnosis and follow
      up. X-ray is a kind of ionizing radiation and leads to formation of oxygen free
      radicals which are capable of damage to DNA, thus altered gen expression and
      mutation. p53 tumor suppressor gene plays a crucial role in the damage response.
      It controls the checkpoint of cell cycle and redirects the cell metabolism to
      either repair of damaged DNA or apoptosis as response to DNA damage. The aim of
      the present study was to examine serum levels of 8-Hydroxydeoxyguanosine (8
      OHdG), a strongly mutagenic product of oxidative DNA damage, p53, superoxide
      dismutase (SOD) and glutathione peroxidase (G-Px), as antioxidant activity, in
      children with scoliosis who had got whole spine radiograph two times during the
      last year. METHODS: A total of 31 children with adolescent idiopathic scoliosis
      and 21 age-matched healthy children were included in the study. Serum levels of 8
      OHdG and p53 were measured with ELISA kits. SOD and G-Px activities were
      determined with spectrophotometric assays. RESULTS: Serum levels of 8-OHdG and
      p53 were found to be higher (P<0.001 and P<0.01, respectively), SOD activity was
      found to be lower (P<0.001) in the children with scoliosis as compared to age
      matched controls. There was no significant difference between the groups for G-Px
      activity. CONCLUSION: Our data show that X-ray exposure causes increased 8-OHdG
      level, and decreased SOD activity, which both may reflect a tumor promoting
      condition. Increased p53 level may be interpreted as a compensatory effort of
      cell to X-ray mediated DNA damage.

PMID- 25941132
TI  - Analysis of prognostic risk factors in children with Epstein-Barr virus
      associated hemophagocytic syndrome.
AB  - AIM: This study aims to analyze the prognostic risk factors in children with
      Epstein-Barr virus-associated haemophagocytic lymphohistiocytosis (EBV-HLH).
      METHODS: Seventy-four EBV-HLH patients were divided into two groups according to
      the specificity: clinical remission after four-week inductive therapy group and
      active disease group; death group and survival group. The risk factors that
      affect early efficacy and prognosis were analyzed. RESULTS: Overall survival rate
      of the 74 children was 75.7%, while the recurrence rate was 13.5%. The one-year
      survival rate was 71.4+/-5.6%, and the three-year survival rate was 65.9+/-6.6%,
      with a median survival rate of 40+/-19.9 months. The multivariate logistic
      regression analysis showed that age was the primary risk factor that affected the
      first 4 weeks alleviation, and the severity of splenomegaly and WBC level upon
      hospitalization were the risk factors that affected the prognosis. Patients with
      spleen>4 cm had shorter survival time than those with spleen<=4 cm, and patients
      with WBC>=3*10(9)/L had longer survival time than those with WBC<3*10(9)/L, which
      exhibited significant differences. CONCLUSION: Age negatively influences the
      early remission of EBV-HLH. WBC<3*10(9)/L and spleen>4 cm exhibited high
      correlation with the prognosis of EBV-HLH.

PMID- 25941133
TI  - [Osteomyelitis: a probable, uncommon etiology agent].
AB  - The relation of infectious agents to arthritis is an area of great interest to
      the rheumatologist. Septic arthritis of bacterial origin accounts for
      approximately 6.5% of all childhood arthritides. Septic arthritis usually results
      from haematogenous spread from a focus of infection elsewhere in the body, but
      also by direct extension of an infection from overlying soft tissues or bone or
      traumatic invasion of the joint. As a result, if a focus of underlying
      osteomyelitis breaks throught the metaphysis, it may enter the joint and result
      in septic arthritis. Systemic signs of illness are fever, severe bone pain, and
      tenderness with or without local swelling. A wide range of microorganism can
      cause septic arthritis in children; Staphylococcus aureus and nongroup A and B
      streptococci are most common overall. However, different organisms are more
      common at some ages and in certain circumstances. Kingella kingae is an emerging
      pathogen in young children under 4 years of age. The clinical presentation of K.
      kingae invasive infection is often subtle and may be associated to mild to
      moderate biologic inflammatory responses. Affected children often have few signs
      and symptoms of osteoarticular infections. Early MRI is useful in differentiating
      K kingae from Gram-positive cocci in osteoarticular infections. Cartilaginous
      involvement, modest soft tissue and bone reaction suggest K. kingae. It's very
      important to include K. kingae in differential diagnosis of osteoarticular
      infections in young children. We report an unusual case of osteomyelitis:
      clinical manifestations and MRI are suggestive for K kingae infection. 

PMID- 25941134
TI  - Mechanisms of apical-basal axis orientation and epithelial lumen positioning.
AB  - In epithelial cells, the polarized orientation of the apical-basal axis
      determines the position of the apical lumen and, thereby, the collective tubular
      tissue architecture. From recent studies employing 3D cell cultures, animal
      models, and patient material, a model is emerging in which the orientation and
      positioning of the apical surface and lumen is controlled by the relationships
      between the extracellular matrix (ECM), Rho family GTPase signaling, recycling
      endosome dynamics, and cell division. Different epithelial cells adjust these
      relationships to establish their specific cell polarity orientation and lumen
      positioning, according to physiologic need. We provide an overview of the
      molecular mechanisms required to construct and orient the apical lumen. 

PMID- 25941135
TI  - Early osteoarthritis of the trapeziometacarpal joint is not associated with joint
      instability during typical isometric loading.
AB  - The saddle-shaped trapeziometacarpal (TMC) joint contributes importantly to the
      function of the human thumb. A balance between mobility and stability is
      essential in this joint, which experiences high loads and is prone to
      osteoarthritis (OA). Since instability is considered a risk factor for TMC OA, we
      assessed TMC joint instability during the execution of three isometric functional
      tasks (key pinch, jar grasp, and jar twist) in 76 patients with early TMC OA and
      44 asymptomatic controls. Computed tomography images were acquired while subjects
      held their hands relaxed and while they applied 80% of their maximum effort for
      each task. Six degree-of-freedom rigid body kinematics of the metacarpal with
      respect to the trapezium from the unloaded to the loaded task positions were
      computed in terms of a TMC joint coordinate system. Joint instability was
      expressed as a function of the metacarpal translation and the applied force. We
      found that the TMC joint was more unstable during a key pinch task than during a
      jar grasp or a jar twist task. Sex, age, and early OA did not have an effect on
      TMC joint instability, suggesting that instability during these three tasks is
      not a predisposing factor in TMC OA.

PMID- 25941136
TI  - Active pollinator choice by Heliconia 'fits the bill'.
AB  - A new study documents that a tropical plant only reproduces when pollen has been
      deposited by a visitor capable of extracting nectar from its deep flowers. Large,
      long-billed hummingbirds generally carry greater quantities of, and more
      genetically diverse, pollen. Thus, plants can exert more active partner choice
      than previously considered possible. 

PMID- 25941138
TI  - Teaching dental practice management in a time of change.

PMID- 25941139
TI  - Will Large DSO-Managed Group Practices Be the Predominant Setting for Oral Health
      Care by 2025? Two Viewpoints: Viewpoint 1: Large DSO-Managed Group Practices Will
      Be the Setting in Which the Majority of Oral Health Care Is Delivered by 2025 and
      Viewpoint 2: Increases in DSO-Managed Group Practices Will Be Offset by Models
      Allowing Dentists to Retain the Independence and Freedom of a Traditional
      Practice.
AB  - This Point/Counterpoint article discusses the transformation of dental practice
      from the traditional solo/small-group (partnership) model of the 1900s to large
      Dental Support Organizations (DSO) that support affiliated dental practices by
      providing nonclinical functions such as, but not limited to, accounting, human
      resources, marketing, and legal and practice management. Many feel that DSO
      managed group practices (DMGPs) with employed providers will become the setting
      in which the majority of oral health care will be delivered in the future.
      Viewpoint 1 asserts that the traditional dental practice patterns of the past are
      shifting as many younger dentists gravitate toward employed positions in large
      group practices or the public sector. Although educational debt is relevant in
      predicting graduates' practice choices, other variables such as gender, race, and
      work-life balance play critical roles as well. Societal characteristics
      demonstrated by aging Gen Xers and those in the Millennial generation blend
      seamlessly with the opportunities DMGPs offer their employees. Viewpoint 2
      contends the traditional model of dental care delivery-allowing entrepreneurial
      practitioners to make decisions in an autonomous setting-is changing but not to
      the degree nor as rapidly as Viewpoint 1 professes. Millennials entering the
      dental profession, with characteristics universally attributed to their
      generation, see value in the independence and flexibility that a traditional
      practice allows. Although DMGPs provide dentists one option for practice, several
      alternative delivery models offer current dentists and future dental school
      graduates many of the advantages of DMGPs while allowing them to maintain the
      independence and freedom a traditional practice provides. 

PMID- 25941140
TI  - ADEA/AAL Institute for Allied Health Educators: Program Evaluation.
AB  - Revised accreditation standards for dental and dental hygiene education programs
      have increased emphasis on faculty development that can improve teaching and
      learning, foster curricular change including use of teaching and learning
      technologies, and enhance retention and satisfaction of faculty. The American
      Dental Education Association (ADEA) and Academy for Academic Leadership (AAL)
      established the Institute for Allied Health Educators (IAHE) in 2007 to address
      faculty development needs for allied dental and allied health educators. In 2009,
      it was transitioned to an online program, which resulted in increased enrollment
      and diversity of participants. After seven years, a comprehensive program
      evaluation was warranted. The authors developed an online questionnaire based on
      Kirkpatrick's four-level model of training evaluation; for this study, levels one
      (satisfaction), two (knowledge and skill acquisition), and three (behavior
      change) were examined. Of the 400 program participants invited to take part in
      the study, a 38% response rate was achieved, with the majority indicating full
      time faculty status. Nearly all (95-97%) of the respondents agreed or strongly
      agreed the program contributed to their teaching effectiveness, and 88-96% agreed
      or strongly agreed it enhanced their knowledge of educational concepts and
      strategies. In addition, 83% agreed or strongly agreed the program helped them
      develop new skills and confidence with technology, with 69% agreeing or strongly
      agreeing that it helped them incorporate technology into their own educational
      setting. Nearly 90% were highly positive or positive in their overall assessment
      of the program; 95% indicated they would recommend it to a colleague; and 80%
      agreed or strongly agreed they had discussed what they learned with faculty
      colleagues at their home institutions who had not attended the program. Positive
      findings from this evaluation provide evidence that the IAHE has been able to
      meet its goals. 

PMID- 25941141
TI  - Sleep medicine content in dental hygiene education.
AB  - According to the National Research Council, 70 million Americans chronically
      suffer from approximately 60 medically recognized sleep disorders. With most
      clinicians unaware of these disorders, many individuals remain undiagnosed. To
      effectively address this issue, health care professionals must work
      collaboratively to educate, identify, and treat patients with sleep disorders.
      However, medical and dental clinicians do not receive adequate education in sleep
      medicine. On the frontline regarding prevention and counseling, dental hygienists
      play an important role in patient education, screening, and management of sleep
      disorders. The aim of this study was to assess the amount of sleep medicine
      content in U.S. dental hygiene programs. An electronic survey was emailed to all
      334 accredited U.S. dental hygiene programs. The 18-question survey assessed the
      sleep medicine content presented during the 2012-13 academic year. A total of
      35.3% (n=118) of the programs responded. The mean number of hours devoted to
      sleep medicine in their curricula was 1.55 hours (SD=1.37). Although 69% (n=79)
      of the responding programs reported spending time on sleep bruxism (mean=1.38
      hours, SD=0.85), only 28% (n=32) reported spending time on other topics such as
      snoring and obstructive sleep apnea (mean=1.39 hours, SD=0.72). These results
      suggest that sleep medicine is included in the majority of U.S. dental hygiene
      programs, but the content is limited and focused on sleep bruxism. This level of
      training is inadequate to prepare dental hygienists for their potential role in
      patient education, screening, and management of sleep-related breathing
      disorders. 

PMID- 25941137
TI  - Features of hepatitis C virus infection, current therapies and ongoing clinical
      trials in ten Asian Pacific countries.
AB  - Estimated hepatitis C virus (HCV) infection rates in the general populations were
      1.3, 0.9, 0.4-1.0, 14.7, 0.1-0.3, 0.9-1.9, 1.0-2.0, 5, 4.4-8.6 and 0.5-1.3 % in
      Australia, Bangladesh, Mainland China, Egypt, Hong Kong, India, Japan, Pakistan,
      Taiwan and Turkey, respectively. The main HCV genotypes (Gs) are G1, G3, G1b, G4,
      G1b, G3, G1b, G3, G1b and G2, and G1 in Australia, Bangladesh, Mainland China,
      Egypt, Hong Kong, India, Japan, Pakistan, Taiwan and Turkey, respectively. Of
      IL28B genotypes, favorable alleles are ~50 % in Australia and Turkey, but 60-70 %
      in most of the other Asian countries. Peginterferon plus ribavirin is available
      in all ten Asian Pasific countries. In addition, HCV NS3/4A protease inhibitors
      with peginterferon plus ribavirin are currently available in several countries.
      Clinical trials of interferon-free regimens for HCV are ongoing in most of the
      ten Asian Pacific countries.

PMID- 25941142
TI  - Oral and maxillofacial radiologists: career trends and specialty board
      certification status.
AB  - Oral and maxillofacial radiology is the newest specialty to be recognized by the
      American Dental Association, so knowledge about the parameters of this profession
      is in the early stages of development. The aim of this study was to understand
      the current distribution of oral and maxillofacial radiologists (OMFRs) in
      academia and private practice, the nature of their practice, and trends in their
      board certification status. An email describing the study's purpose with a link
      to a survey was sent to "OradList," a listserv that has a majority of OMFRs in
      the United States and Canada as members. Of the 205 respondents, 46% were female;
      the age distribution ranged from 25 to over 70 years; and 80% were working full
      time. Among the respondents, 66% practiced in an academic setting, 20% in private
      practice, 8% in both private and academic settings, and 3% in the military. Only
      37% of the respondents were board-certified. For OMFRs trained from 1965 to 2009,
      there was an increasing trend towards becoming board-certified, but a significant
      decrease occurred after 2009, dropping from 65% to 35% of those trained in those
      years. 

PMID- 25941143
TI  - The winds of change revisited: progress towards building a culture of evidence
      based dentistry.
AB  - In 2008, Texas A&M University Baylor College of Dentistry launched a
      comprehensive four-year curriculum in evidence-based dentistry (EBD) along with a
      series of faculty development initiatives to create an EBD culture. The aim of
      this study was to determine the institution's success in achieving this goal. The
      assessment tool used was the PEAK instrument, which measures respondents' EBD
      Practices, Experience, Attitudes, and Knowledge. Two EBD-trained classes of
      students and one class untrained in EBD (approximately 100 students in each
      class) were assessed annually. The faculty were assessed before and after
      completion of the initiative. Nearly all students responded, with samples ranging
      from 87 to 102; the faculty response rates were 53% (62/117) in 2009 and 66% in
      2013 (81/123). In the results, the trained students scored significantly higher
      in knowledge than the untrained students at each of the first three PEAK
      administrations (p<=0.001). Regarding confidence in appraising a research report,
      the first trained group significantly gained in appropriate use of statistical
      tests (p<0.001), while the second trained group significantly gained in this
      aspect and five others (p<=0.032). At the final PEAK administration, the second
      trained group agreed more than the untrained group that EBD was important for the
      practice of dentistry (p<0.001). Faculty comfort level with reading peer-reviewed
      articles increased significantly from 2009 to 2013 (p=0.039). Faculty members who
      participated in the summer EBD Fundamentals course (n=28) had significantly
      higher EBD knowledge scores than those who did not participate (p=0.013), and
      their EBD attitudes and practices were more positive (p<0.05). Students and
      faculty trained in EBD were more knowledgeable and exhibited more positive
      attitudes, supporting a conclusion that the college has made substantial progress
      towards achieving an EBD culture. 

PMID- 25941144
TI  - Grand rounds for dental students: an exploration.
AB  - Grand Rounds are widely used in medicine for educating students comprehensively
      about clinical issues. The aim of this study was to explore the value of Grand
      Rounds for introducing first- (D1) and second-year (D2) dental students to an
      interdisciplinary approach to dental care. The objectives were to explore how
      interested students were in various topics, which topics they would like to see
      addressed in future sessions, which aspects they liked/disliked, how they
      evaluated the program components, and how they evaluated the outcomes. Data were
      collected from D1s at the end of the Year 1 fall term and from D1s and D2s at the
      beginning and end of the Year 1 winter term and at the end of Year 2. Response
      rates for most of the groups ranged from 88% to 100%, but response rates for
      surveys at the end of the study period fell to 40% and 32%. The results showed
      that the students were most interested in clinical topics that were presented in
      an interdisciplinary way. Their suggested topics ranged from specialty-specific
      issues to treatment-related topics such as implants and cosmetic dentistry. The
      open-ended responses showed that students liked learning differing perspectives
      on these topics, but disliked the course-related assignments and the preparation
      work in small groups. The closed-ended responses showed that the students
      appreciated the in-class presentations by experts and evaluated the course as
      helpful in informing them about the complexity of issues and the importance of
      the interplay between basic and clinical sciences. Educating future dentists in a
      way in which they embrace interdisciplinary approaches is challenging. Using the
      Grand Rounds concept could be one approach to increasing students' awareness of
      the importance of interdisciplinary work. 

PMID- 25941145
TI  - Implementation of a patient-centered approach to clinical dental education: a
      five-year reflection.
AB  - The intent of the redesign of the clinical component of the Harvard School of
      Dental Medicine (HSDM) curriculum from a traditional numerical procedures-based
      system to a patient-based comprehensive care system was to improve both patient
      care and student learning. The aim of this retrospective cohort study was to
      evaluate the outcomes of and students' perspectives on this patient-centered
      comprehensive care model introduced in 2009. Data were obtained from the school's
      Office of Dental Education for a study sample consisting of 205 fourth-year
      dental students in the graduating classes of 2009 through 2014 at HSDM. The
      results showed that students were completing more than the required number of
      comprehensive patient cases on average. A survey given to the Class of 2014 found
      that the respondents (35 of 36 students) were generally satisfied with the new
      curriculum and the clinical experience in relation to continuation of care and
      perceptions of comprehensive care. The results of this study suggest that the
      redesigned patient-centered assessment model of the clinical component of the
      curriculum helped improve patient care and student learning. 

PMID- 25941146
TI  - The association of patients' oral health literacy and dental school communication
      tools: a pilot study.
AB  - The aim of this pilot study was to assess adult patients' ability to read and
      understand two communication tools at the University of California, Los Angeles,
      School of Dentistry: the dental school clinic website and a patient education
      brochure pertaining to sedation in children that was written by dental school
      personnel. A convenience sample of 100 adults seeking treatment at the school's
      general dental clinic during 2012-13 completed a health literacy screening
      instrument. They were then asked to read clinic educational and informational
      materials and complete a survey. Analyses were conducted to determine the
      association between the subjects' oral health literacy and sociodemographics and
      their ability to locate and interpret information in written oral health
      information materials. SMOG and Flesch-Kincade formulas were used to assess the
      readability level of the electronic and written communication tools. The results
      demonstrated an association between these adults' oral health literacy and their
      dental knowledge and ability to navigate health information website resources and
      understand health education materials. Health literacy was not associated with
      age or gender, but was associated with education and race/ethnicity. The SMOG
      Readability Index determined that the website and the sedation form were written
      at a ninth grade reading level. These results suggest that dental schools and
      other health care organizations should incorporate a health-literate approach for
      their digital and written materials to enhance patients' ability to navigate and
      understand health information, regardless of their health literacy. 

PMID- 25941147
TI  - Long-term adoption of caries management by risk assessment among dental students
      in a university clinic.
AB  - The aim of this study was to evaluate the long-term adoption of a risk-based
      caries management program at a university dental clinic. The authors extracted
      data from electronic records of adult non-edentulous patients who underwent a
      comprehensive oral evaluation in the university predoctoral clinic from July 2007
      through June 2014 (N=21,984). Consistency with caries management guidelines was
      measured as the percentage of patients with caries risk designation (low,
      moderate, high, or extreme) and the percentage of patients provided non-operative
      anti-caries agents within each designated caries risk category. Additionally,
      patient and provider characteristics associated with risk assessment completion
      and with provision of anti-caries therapy were identified. Results showed that
      the percentage of patients with documented caries risk grew steadily from 62.3%
      in 2007-08 to 92.8% in 2013-14. Overall, receipt of non-operative anti-caries
      agents increased with rising caries risk, from low (6.9%), moderate (14.1%), high
      (36.4%), to extreme (51.4%), but percentages were stable over the study period.
      Younger patients were more likely to have a completed risk assessment, and among
      high- and extreme-risk patients, delivery of anti-caries therapy was more common
      among patients who were younger, identified as Asian or Caucasian, received
      public dental benefits, or were seen by a student in the four-year DDS program or
      in the final year of training. These results demonstrate that extensive
      compliance in documenting caries risk was achieved within a decade of
      implementing risk-based clinical guidelines at this dental school clinic. Caries
      risk was the most strongly associated of several factors related to delivery of
      non-operative therapy. The eventual success of this program suggests that, in
      dental education, transition to a risk-based, prevention-focused curriculum may
      require a long-term commitment. 

PMID- 25941148
TI  - Incidence of Sleep Disorders Reported by Patients at UTHSC College of Dentistry:
      A Two-Year Follow-Up and Proposed Educational Program.
AB  - A 2011 study at one U.S. dental school found that patients were not routinely
      screened by dental students for obstructive sleep apnea and/or other related
      sleep disorders, nor were students being trained to screen. Consequently, the
      medical history questionnaire used in the clinic was updated to include five
      specific screening questions. The aim of this two-year follow-up study was to
      determine whether screening had improved at the school. A retrospective chart
      review of all patients (age 14-70+) in the third- and fourth-year dental clinics
      in 2012 and 2013 searched for "YES" responses to the five questions. Of 5,931
      patients, 38% reported they snore or were told they snore. By age 50-59, their
      reports of snoring increased to 50%. About 5% reported incidents waking up
      choking. By age 50, between one-fifth and one-quarter indicated they woke up
      frequently during the night. One in six frequently felt overly tired during the
      daytime, often falling asleep. This problem was evenly reported by all age groups
      between ages 30 and 69. About half the patients reporting sleep problems also had
      hypertension and cardiovascular problems with an equal distribution between males
      and females. The results showed that updating the medical history form had
      dramatically improved screening for sleep-disordered breathing by these dental
      students. Though screening is neither a definitive diagnosis nor an attempt to
      distinguish among sleep disorders, the results correlate with national
      statistics. Screening is an important step to increase student awareness of this
      serious health trend as it prepares students to engage more constructively in its
      management and referral. 

PMID- 25941149
TI  - Relationship between hand-skill exercises and other admissions criteria and
      students' performance in dental school.
AB  - The aim of this study was to investigate the existence of correlations between
      dental admissions criteria, including a chalk carving exercise, and students'
      subsequent academic performance. The retrospective cohort study examined the
      records of dental students at Louisiana State University Health Science Center
      School of Dentistry for the years 1998 to 2008. Only those students who could be
      categorized into the following four groups were included: 1) those who graduated
      in the top 10% of their class, 2) those who graduated in the bottom 10% of their
      class, 3) those who repeated a year of dental school, and 4) those who were
      dismissed or resigned. The study sample consisted of 176 students: 62 in the
      first group, 62 in the second group, 25 in the third group, and 27 in the fourth
      group. Data collected were each student's undergraduate grade point average
      (GPA); chalk carving score; undergraduate biology, chemistry, physics (BCP) GPA;
      Dental Admission Test (DAT) Academic Average; Perceptual Ability Test (PAT) score
      of the DAT; total DAT score; grade in preclinical operative dentistry class;
      grade in morphology and occlusion class; and dental school GPA at graduation. The
      results showed that only the undergraduate GPA and BCP GPA were significantly
      higher for students in the top 10% of their class than for other groups. The only
      positive correlation involving the chalk carving scores was with the preclinical
      operative dentistry course grade. This study thus found limited correlations
      between this institution's admissions criteria and its students' success in
      dental school. 

PMID- 25941150
TI  - Implementation of a flipped classroom educational model in a predoctoral dental
      course.
AB  - This article describes the development and implementation of a flipped classroom
      model to promote student-centered learning as part of a predoctoral dental
      course. This model redesigns the traditional lecture-style classroom into a
      blended learning model that combines active learning pedagogy with instructional
      technology and "flips" the sequence so that students use online resources to
      learn content ahead of class and then use class time for discussion. The dental
      anatomy portion of a second-year DMD course at Harvard School of Dental Medicine
      was redesigned using the flipped classroom model. The 36 students in the course
      viewed online materials before class; then, during class, small groups of
      students participated in peer teaching and team discussions based on learning
      objectives under the supervision of faculty. The utilization of pre- and post
      class quizzes as well as peer assessments were critical motivating factors that
      likely contributed to the increase in student participation in class and helped
      place learning accountability on the students. Student feedback from a survey
      after the experience was generally positive with regard to the collaborative and
      interactive aspects of this form of blended learning. 

PMID- 25941151
TI  - e-Assessment in a Limited-Resources Dental School Using an Open-Source Learning
      Management System.
AB  - e-Assessment provides solutions to some problems encountered in dental students'
      evaluation. The aim of this study was to evaluate the experience of a limited
      resources dental school with e-assessment provided through an open-source
      learning management system (LMS). Data about users' access and types of e
      assessment activities at the Faculty of Dentistry, Alexandria University, Egypt,
      were obtained from the web-based LMS Moodle. A questionnaire developed to assess
      students' perceptions of the e-assessment was also sent to students registered in
      two courses (undergraduate and postgraduate) with the same instructor. The
      results showed that most e-courses at the school had one form of e-assessment
      (82%) and, of these, 16.7% had summative assessment activities. There were
      significant differences among departments in the number of e-courses with e
      assessment. One-quarter of e-courses with e-assessment used Moodle quizzes. Of
      285 students registered in the two courses that included the questionnaire, 170
      responded (response rate=59.6%). The responding students positively perceived the
      impact of e-assessment on learning and its reliability and security, whereas
      technical issues and related stresses were negatively perceived. This study
      suggests that e-assessment can be used at minimal cost in dental schools with
      limited resources and large class sizes with the least demands on faculty members
      and teaching staff time. For these schools, an open-source LMS such as Moodle
      provides formative e-assessment not available otherwise and accommodates various
      question formats and varying levels of instructors' technical skills. These
      students seemed to have a positive impression of the e-assessment although
      technical problems and related stresses are issues that need to be addressed. 

PMID- 25941152
TI  - Health promotion training in dental and oral health degrees: a scoping review.
AB  - Dental diseases are a major burden on health; however, they are largely
      preventable. Dental treatment alone will not eradicate dental disease with a
      shift to prevention required. Prevention of dental diseases is a role of dental
      professionals, with most countries having formalized health promotion
      competencies for dental and oral health graduates. In spite of this, there may be
      minimal health promotion being undertaken in clinical practice. Therefore, the
      aim of this study was to conduct a scoping review to identify some published
      studies on health promotion training in dental and oral health degrees. Key
      search terms were developed and used to search selected databases, which
      identified 84 articles. Four articles met the inclusion/exclusion criteria and
      were included in the review. Of these studies, the type of oral health promotion
      tasks and instructions received before the tasks varied. However, for all studies
      the health promotion content was focused on health education. In terms of
      evaluation of outcomes, only two studies evaluated the health promotion content
      using student reflections. More good-quality information on health promotions
      training is needed to inform practice. 

PMID- 25941153
TI  - Restriction of glucose and fructose causes mild oxidative stress independently of
      mitochondrial activity and reactive oxygen species in Drosophila melanogaster.
AB  - Our recent study showed different effects of glucose and fructose overconsumption
      on the development of obese phenotypes in Drosophila. Glucose induced glucose
      toxicity due to the increase in circulating glucose, whereas fructose was more
      prone to induce obesity promoting accumulation of reserve lipids and
      carbohydrates (Rovenko et al., Comp. Biochem. Physiol. A Mol. Integr. Physiol.
      2015, 180, 75-85). Searching for mechanisms responsible for these phenotypes in
      this study, we analyzed mitochondrial activity, mitochondrial density, mtROS
      production, oxidative stress markers and antioxidant defense in fruit flies fed
      0.25%, 4% and 10% glucose or fructose. It is shown that there is a complex
      interaction between dietary monosaccharide concentrations, mitochondrial activity
      and oxidative modifications to proteins and lipids. Glucose at high concentration
      (10%) reduced mitochondrial protein density and consequently respiration in
      flies, while fructose did not affect these parameters. The production of ROS by
      mitochondria did not reflect activities of mitochondrial complexes. Moreover,
      there was no clear connection between mtROS production and antioxidant defense or
      between antioxidant defense and developmental survival, shown in our previous
      study (Rovenko et al., Comp. Biochem. Physiol. A Mol. Integr. Physiol. 2015, 180,
      75-85). Instead, mtROS and antioxidant machinery cooperated to maintain a redox
      state that determined survival rates, and paradoxically, pro-oxidant conditions
      facilitated larva survival independently of the type of carbohydrate. It seems
      that in this complex system glucose controls the amount of oxidative modification
      regulating mitochondrial activity, while fructose regulates steady-state mRNA
      levels of antioxidant enzymes. 

PMID- 25941155
TI  - Divergent reactivity in palladium-catalyzed annulation with diarylamines and
      alpha,beta-unsaturated acids: direct access to substituted 2-quinolinones and
      indoles.
AB  - A palladium-catalyzed C?H activation strategy has been successfully employed for
      exclusive synthesis of a variety of 3-substituted indoles. A [3+3] annulation for
      synthesizing substituted 2-quinolinones was recently developed by reaction of
      alpha,beta-unsaturated carboxylic acids with diarylamines under acidic
      conditions. In the present work, an analogous [3+2] annulation is achieved from
      the same set of starting materials under basic conditions to generate 1,3
      disubstituted indoles exclusively. Mechanistic studies revealed an ortho
      palladation-pi-coordination-beta-migratory insertion-beta-hydride elimination
      reaction sequence to be operative under the reaction conditions. 

PMID- 25941154
TI  - Polymorphisms in the mitochondrially encoded ATP synthase 8 gene are associated
      with susceptibility to bullous pemphigoid in the German population.

PMID- 25941156
TI  - Metabolomic analysis of the green microalga Chlamydomonas reinhardtii cultivated
      under day/night conditions.
AB  - Biomass composition of Chlamydomonas reinhardtii was studied during two
      consecutive cycles of 12h light/12h dark. As in our experimental conditions the
      two synchronized divisions were separated by 20h, it was possible to show that
      accumulation of dry weight, proteins, chlorophyll and fatty acids mainly depends
      on cell division, whereas starch accumulation depends on a circadian rhythm as
      reported previously. Our metabolomics analyses also revealed that accumulation of
      five (Ser, Val, Leu, Ile and Thr) of the nine free amino acids detected displayed
      rhythmicity, depending on cell division while Glu was 20-50 times more abundant
      than the other ones probably because this free amino acid serves not only for
      protein synthesis but also for biosynthesis of nitrogen compounds. In addition,
      we performed a thermodynamic-motivated theoretical approach known as 'surprisal
      analysis'. The results from this analysis showed that cells were close to a
      steady state all along the 48h of the experiment. In addition, calculation of
      free energy of cellular metabolites showed that the transition point, i.e. the
      state which immediately precedes cell division, corresponds to the most unstable
      stage of the cell cycle and that division is identified as the greatest drop in
      the free energy of metabolites. 

PMID- 25941158
TI  - The role of alexithymia in quality of life impairment in patients with chronic
      hepatitis C during antiviral treatment.
AB  - This study aimed to investigate the role of alexithymia in the quality of life of
      patients with chronic hepatitis C treated with antiviral therapy. A consecutive
      sample of 124 patients were evaluated at baseline, during, and 6months after
      treatment with interferon and ribavirin. At baseline past mood disorders and
      alexithymia and, at each index visit, adverse events, psychological distress, and
      disease-specific quality of life were assessed with validated instruments.
      Patients with past mood disorders and alexithymia had impaired levels of quality
      of life, psychological distress, and treatment-related adverse events. However,
      after controlling for covariates, poor quality of life was independently
      predicted by alexithymia and psychological distress before (R(2)=0.60) and
      6months after (R(2)=0.69) the antiviral treatment while during treatment (at
      3months and the end of therapy) by depression and somatic adverse events
      (R(2)=0.67 and 0.69, respectively). Alexithymia rather than history of mood
      disorders resulted to be an independent predictor of impaired quality of life not
      only before but also 6months after the end of treatment. Given the association
      with proneness to health-compromising behaviors, clinicians are encouraged to pay
      closer attention to long-term psychological and somatic effects of antiviral
      treatment in patients with alexithymic characteristics. 

PMID- 25941159
TI  - Erratum to: Revisional Laparoscopic Gastric Pouch Resizing for Inadequate Weight
      Loss After Roux-en-Y Gastric Bypass.

PMID- 25941157
TI  - Isolation of a maize ZmCI-1B promoter and characterization of its activity in
      transgenic maize and tobacco.
AB  - KEY MESSAGE: The 2-kb ZmCI - 1B promoter is active in the root and embryo and
      induced by wounding in maize and the 220-bp 5'-deleted segment maybe the minimal
      promoter. The subtilisin-chymotrypsin inhibitor gene, CI-1B of Zea mays (ZmCI
      1B), has been suggested to induce the maize defense system to resist insect
      attack. Real-time RT-PCR showed that ZmCI-1B gene exhibited especially high
      expression in roots and embryos. The 2-kb full-length promoter of ZmCI-1B gene
      was isolated from the maize genome and used to drive expression of a beta
      glucuronidase (GUS) reporter gene for transient expression and stable expression
      analysis in maize. The results of GUS histochemical staining in transgenic maize
      plants revealed that the ZmCI-1B promoter induced GUS expression preferentially
      in roots and embryos and in response to wounding. A series of 5'-deleted segments
      of the ZmCI-1B promoter were cloned individually to drive GUS expression for
      further analysis. Deletion analysis combined with the histochemical staining of
      transgenic tobacco plants revealed 220-bp segment could drive GUS in a tissue
      specific and wounding-induced expression in tobacco; thus, it maybe the minimally
      active promoter of ZmCI-1B gene. Furthermore, it revealed that the ZmCI-1B
      promoter contained tissue-specific and wounding-induced elements.

PMID- 25941160
TI  - Combination of the dipeptidyl peptidase-4 inhibitor linagliptin with insulin
      based regimens in type 2 diabetes and chronic kidney disease.
AB  - Glucose-lowering treatment options for type 2 diabetes mellitus patients with
      chronic kidney disease are limited. We evaluated the potential for linagliptin in
      combination with insulin in type 2 diabetes mellitus patients with mild-to-severe
      renal impairment. Data for participants in two phase 3 trials with linagliptin
      who were receiving insulin were analysed separately (n = 811). Placebo-adjusted
      mean HbA1c changes from baseline were -0.59% (mild renal impairment) and -0.69%
      (moderate renal impairment) after 24 weeks and -0.43% (severe renal impairment)
      after 12 weeks. Drug-related adverse events with linagliptin were similar to
      placebo (mild renal impairment: 19.9% vs. 26.5%; moderate renal impairment: 22.0%
      vs. 25.0%; severe renal impairment: 46.3% vs. 43.6%, respectively). Frequencies
      of hypoglycaemia in patients with mild, moderate and severe renal impairment were
      34.9%, 35.6% and 66.7% with linagliptin and 37.5%, 39.7% and 49.1% with placebo,
      respectively. Episodes of severe hypoglycaemia were low (?5.6%). Adding
      linagliptin to insulin in type 2 diabetes mellitus patients with chronic kidney
      disease improved glucose control and was well tolerated.

PMID- 25941161
TI  - Metabolic abnormalities of the heart in type II diabetes.
AB  - Type 2 diabetes mellitus escalates the risk of heart failure partly via its
      ability to induce a cardiomyopathic state that is independent of coronary artery
      disease and hypertension. Although the pathogenesis of diabetic cardiomyopathy
      has yet to be fully elucidated, aberrations in cardiac substrate metabolism and
      energetics are thought to be key drivers. These aberrations include excessive
      fatty acid utilisation and storage, suppressed glucose oxidation and impaired
      mitochondrial oxidative phosphorylation. An appreciation of how these
      abnormalities arise and synergise to promote adverse cardiac remodelling is
      critical to their effective amelioration. This review focuses on disturbances in
      myocardial fuel (fatty acids and glucose) flux and energetics in type 2 diabetes,
      how these disturbances relate to the development of diabetic cardiomyopathy and
      the potential therapeutic agents that could be used to correct them. 

PMID- 25941162
TI  - Graphics Processing Unit-Based Bioheat Simulation to Facilitate Rapid Decision
      Making Associated with Cryosurgery Training.
AB  - This study focuses on the implementation of an efficient numerical technique for
      cryosurgery simulations on a graphics processing unit as an alternative means to
      accelerate runtime. This study is part of an ongoing effort to develop
      computerized training tools for cryosurgery, with prostate cryosurgery as a
      developmental model. The ability to perform rapid simulations of various test
      cases is critical to facilitate sound decision making associated with medical
      training. Consistent with clinical practice, the training tool aims at
      correlating the frozen region contour and the corresponding temperature field
      with the target region shape. The current study focuses on the feasibility of
      graphics processing unit-based computation using C++ accelerated massive
      parallelism, as one possible implementation. Benchmark results on a variety of
      computation platforms display between 3-fold acceleration (laptop) and 13-fold
      acceleration (gaming computer) of cryosurgery simulation, in comparison with the
      more common implementation on a multicore central processing unit. While the
      general concept of graphics processing unit-based simulations is not new, its
      application to phase-change problems, combined with the unique requirements for
      cryosurgery optimization, represents the core contribution of the current study. 

PMID- 25941163
TI  - Simulation-Based Cryosurgery Intelligent Tutoring System Prototype.
AB  - As a part of an ongoing effort to develop computerized training tools for
      cryosurgery, the current study presents a proof of concept for a computerized
      tool for cryosurgery tutoring. The tutoring system lists geometrical constraints
      of cryoprobes placement, simulates cryoprobe insertion, displays a rendered shape
      of the prostate, enables distance measurements, simulates the corresponding
      thermal history, and evaluates the mismatch between the target region shape and a
      preselected planning isotherm. The quality of trainee planning is measured in
      comparison with a computer-generated planning, created for each case study by
      previously developed planning algorithms. The following two versions of the
      tutoring system have been tested in the current study: (1) an unguided version,
      where the trainee can practice cases in unstructured sessions and (2) an
      intelligent tutoring system, which forces the trainee to follow specific steps,
      believed by the authors to potentially shorten the learning curve. Although the
      tutoring level in this study aims only at geometrical constraints on cryoprobe
      placement and the resulting thermal histories, it creates a unique opportunity to
      gain insight into the process outside the operation room. Post-test results
      indicate that the intelligent tutoring system may be more beneficial than the
      nonintelligent tutoring system, but the proof of concept is demonstrated with
      either system. 

PMID- 25941164
TI  - Alberto Gulino MD, PhD (1952-2014).

PMID- 25941165
TI  - What a 'Ku'incidence!: parallel discoveries of a new DNA repair factor.

PMID- 25941166
TI  - XLS (c9orf142) is a new component of mammalian DNA double-stranded break repair.
AB  - Repair of double-stranded DNA breaks (DSBs) in mammalian cells primarily occurs
      by the non-homologous end-joining (NHEJ) pathway, which requires seven core
      proteins (Ku70/Ku86, DNA-PKcs (DNA-dependent protein kinase catalytic subunit),
      Artemis, XRCC4-like factor (XLF), XRCC4 and DNA ligase IV). Here we show using
      combined affinity purification and mass spectrometry that DNA-PKcs co-purifies
      with all known core NHEJ factors. Furthermore, we have identified a novel
      evolutionary conserved protein associated with DNA-PKcs-c9orf142. Computer-based
      modelling of c9orf142 predicted a structure very similar to XRCC4, hence we have
      named c9orf142-XLS (XRCC4-like small protein). Depletion of c9orf142/XLS in cells
      impaired DSB repair consistent with a defect in NHEJ. Furthermore, c9orf142/XLS
      interacted with other core NHEJ factors. These results demonstrate the existence
      of a new component of the NHEJ DNA repair pathway in mammalian cells. 

PMID- 25941167
TI  - Slingshot-Cofilin activation mediates mitochondrial and synaptic dysfunction via
      Abeta ligation to beta1-integrin conformers.
AB  - Correction to: Cell Death and Differentiation (2015) 22, 921-934;
      doi:10.1038/cdd.2015.5; published online 20 February 2015. Since the publication
      of this paper, the authors have noticed the y-axis label of Figure 7e was
      incorrect. It should be % of the fESP slope. This has now been rectified and the
      corrected article appears in this issue together with this corrigendum.

PMID- 25941169
TI  - Gangliosides: glycosphingolipids essential for normal neural development and
      function.
AB  - Lipid rafts, sites of signal transduction, are enriched in glycosphingolipids
      (GSLs). Gangliosides, a class of GSLs found in greatest concentration in the grey
      matter of the brain, can affect neuronal function by modulating cell signaling.
      This review summarizes changes in ganglioside expression during brain
      development, the specific effects they induce, and makes observations about their
      possible role(s) in dementing diseases. Given that the average lifespan of
      individuals in many countries has increased, and that aging is accompanied by an
      increasing probability of dementia, understanding how changes in the GSL
      composition of lipid rafts may contribute to the cell biological basis of a
      specific dementing phenotype is an important area of study. 

PMID- 25941168
TI  - Emerging structural insights into the function of ionotropic glutamate receptors.
AB  - Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that
      mediate excitatory neurotransmission crucial for brain development and function,
      including learning and memory formation. Recently a wealth of structural studies
      on iGluRs including AMPA receptors (AMPARs), kainate receptors, and NMDA
      receptors (NMDARs) became available. These studies showed structures of non
      NMDARs including AMPAR and kainate receptor in various functional states, thereby
      providing the first visual sense of how non-NMDAR iGluRs may function in the
      context of homotetramers. Furthermore, they provided the first view of
      heterotetrameric NMDAR ion channels, and this illuminated the similarities with
      and differences from non-NMDARs, thus raising a mechanistic distinction between
      the two groups of iGluRs. We review mechanistic insights into iGluR functions
      gained through structural studies of multiple groups. 

PMID- 25941170
TI  - Understanding intramembrane proteolysis: from protein dynamics to reaction
      kinetics.
AB  - Intramembrane proteolysis - cleavage of proteins within the plane of a membrane -
      is a widespread phenomenon that can contribute to the functional activation of
      substrates and is involved in several diseases. Although different families of
      intramembrane proteases have been discovered and characterized, we currently do
      not know how these enzymes discriminate between substrates and non-substrates,
      how site-specific cleavage is achieved, or which factors determine the rate of
      proteolysis. Focusing on gamma-secretase and rhomboid proteases, we argue that
      answers to these questions may emerge from connecting experimental readouts, such
      as reaction kinetics and the determination of cleavage sites, to the structures
      and the conformational dynamics of substrates and enzymes. 

PMID- 25941171
TI  - Worldwide decrease in methicillin-resistant Staphylococcus aureus: do we
      understand something?

PMID- 25941172
TI  - Amino acid residues Leu135 and Tyr236 are required for RNA binding activity of
      CFIm25 in Entamoeba histolytica.
AB  - Pre-mRNA 3' end processing in the nucleus is essential for mRNA stability,
      efficient nuclear transport, and translation in eukaryotic cells. In Human, the
      cleavage/polyadenylation machinery contains the 25 kDa subunit of the Cleavage
      Factor Im (CFIm25), which specifically recognizes two UGUA elements and regulates
      the assembly of polyadenylation factors, poly(A) site selection and
      polyadenylation. In Entamoeba histolytica, the protozoan parasite responsible for
      human amoebiasis, EhCFIm25 has been reported as a RNA binding protein that
      interacts with the Poly(A) Polymerase. Here, we follow-up with the study of
      EhCFIm25 to characterize its interaction with RNA. Using in silico strategy, we
      identified Leu135 and Tyr236 in EhCFIm25 as conserved amino acids among CFIm25
      homologues. We therefore generated mutant EhCFIm25 proteins to investigate the
      role of these residues for RNA interaction. Results showed that RNA binding
      activity was totally abrogated when Leu135 and Tyr236 were replaced with Ala
      residue, and Tyr236 was changed for Phe. In contrast, RNA binding activity was
      less affected when Leu135 was substituted by Thr. Our data revealed for the first
      time -until we know-the functional relevance of the conserved Leu135 and Tyr236
      in EhCFIm25 for RNA binding activity. They also gave some insights about the
      possible chemical groups that could be interacting with the RNA molecule. 

PMID- 25941173
TI  - Generation of neural progenitor cells by chemical cocktails and hypoxia.

PMID- 25941175
TI  - Health gains and financial risk protection: an extended cost-effectiveness
      analysis of treatment and prevention of diarrhoea in Ethiopia.
AB  - OBJECTIVES: Policymakers face many decisions when considering public financing
      for health, including the kind of health interventions to include in a publically
      financed package. The consequences of these choices will influence health
      outcomes as well as the financial risk protection provided to different segments
      of the population. The purpose of this study is to illustrate the size and
      distribution of benefits due to treatment and prevention of diarrhoea (ie,
      rotavirus vaccination). METHODS: We use an economic model to examine the impacts
      of universal public finance (UPF) of diarrhoeal treatment alone, as opposed to
      diarrhoeal treatment along with rotavirus vaccination in Ethiopia using extended
      cost-effectiveness analysis (ECEA). ECEA allows us to measure the health gains
      and financial risk protection provided by these interventions for each wealth
      quintile. Our model compares a baseline situation with diarrhoeal treatment
      seeking of 32% (overall) and no rotavirus vaccination, to a situation where UPF
      increases treatment seeking by 20 percentage points for each quintile and
      rotavirus vaccination reaches DTP (diphteria, pertussis, tetanus) 2 levels for
      each quintile (overall rate of 52%). We calculate deaths averted, private
      expenditures averted and costs incurred by the government under the baseline
      situation and with UPF. RESULTS: We find that diarrhoeal treatment paired with
      rotavirus vaccination is more cost effective than diarrhoeal treatment alone for
      the metrics we examine in this paper (deaths and private expenditures averted).
      Per US$1 million invested, diarrhoeal treatment saves 44 lives and averts
      US$115,000 in private expenditures. For the same investment, diarrhoeal treatment
      and rotavirus vaccination save 61 lives and avert US$150,000 in private
      expenditures. The health benefits of these interventions tend to benefit the
      poor, while the financial benefits favour the better-off. CONCLUSIONS:
      Policymakers should consider multiple benefit streams as well as their scale and
      incidence when considering public finance of health interventions.

PMID- 25941176
TI  - Interaction analysis of the new pooled cohort equations for 10-year
      atherosclerotic cardiovascular disease risk estimation: a simulation analysis.
AB  - OBJECTIVES: To evaluate the individual and interacting impacts of the continuous
      variables (age, total cholesterol (total-C), high-density lipoprotein cholesterol
      (HDL-C) and systolic blood pressure(BP)) on 10-year atherosclerotic
      cardiovascular disease (ASCVD) risk and better understand the pattern of
      predicted 10-year risk with change of each variable using recently published new
      pooled cohort equations. DESIGN: Simulation analysis was performed across the
      whole range of the boundary limits suggested for the continuous variables for
      groupings based on race and gender in the pooled cohort 10-year risk equations.
      SETTING: Computer-based simulation analysis. PARTICIPANTS: Data were generated by
      simulation using prespecified variable ranges. INTERVENTION: Data simulation and
      visual display of the hazard analysis. MAIN OUTCOME MEASURES: Interactions of age
      with other variables were analysed using multidimensional visualisation and
      hazard analysis. RESULTS: In African-American females, due to the interaction of
      age with HDL-C, treated BP and untreated BP, increasing age may not always
      increase 10-year risk. Furthermore, in the same cohort, increasing HDL-C level
      may result in higher 10-year risk for older individuals. For Caucasian females,
      due to square of Ln (age) term in the equation, the age-risk curve does not
      monotonically increase with age. The vertex is within the given age range of 40
      79 years for a certain range of total-C and HDL-C, indicating that age may not
      always result in increased predicted 10-year risk. CONCLUSIONS: The new pooled
      cohort equations are sophisticated as they take into account the interactions of
      the continuous variables in predicting 10-year risk. We find situations where the
      estimated 10-year risk does not follow the general secular trends. The impact of
      such interesting patterns may be substantial and therefore further exploration is
      needed as it has direct implications in clinical management for primary
      prevention.

PMID- 25941174
TI  - Exposure to air pollution and meteorological factors associated with children's
      primary care visits at night due to asthma attack: case-crossover design for 3
      year pooled patients.
AB  - OBJECTIVE: We examined the association of outdoor air pollution and
      meteorological parameters with primary care visits (PCVs) at night due to asthma
      attack. SETTING: A case-crossover study was conducted in a primary care clinic in
      Himeji City, Japan. PARTICIPANTS: Participants were 1447 children aged 0-14 years
      who visited the clinic with an asthma attack from April 2010 until March 2013.
      EXPOSURE: Daily concentrations of air pollutants and meteorological parameters
      were measured. PRIMARY OUTCOME: PCVs at night due to asthma attack. A conditional
      logistic regression model was used to estimate ORs of PCVs per unit increment of
      air pollutants or meteorological parameters (the per-unit increments of
      particulate matter with an aerodynamic diameter <=2.5 um (PM2.5) and ozone were
      10 MUg/m(3) and 10 ppb, respectively). Analyses took into consideration the
      effects of seasonality. RESULTS: We noted an association between PCVs and daily
      ozone levels on the day before a PCV (OR=1.17; 95% CI 1.01 to 1.35; p=0.04), as
      well as between PCVs and 3-day mean ozone levels before a PCV (OR=1.29; 95% CI
      1.00 to 1.46; p=0.04), from April until June. We also observed an association
      between PCVs and daily PM2.5 levels on the day before a PCV from December until
      March (OR=1.16; 95% CI 1.01 to 1.33; p=0.05). Meteorological parameters, such as
      hours of sunshine from September until November, atmospheric pressure from April
      until June, and temperature from April until August, were also found to be
      associated with PCVs. CONCLUSIONS: The findings in the present study supported an
      association between ozone and PCVs and suggest that certain meteorological items
      may be associated with PCVs.

PMID- 25941177
TI  - Managing work-family conflict in the medical profession: working conditions and
      individual resources as related factors.
AB  - OBJECTIVES: This study developed and tested a research model that examined the
      effects of working conditions and individual resources on work-family conflict
      (WFC) using data collected from physicians working at German clinics. MATERIAL
      AND METHODS: This is a cross-sectional study of 727 physicians working in German
      hospitals. The work environment, WFC and individual resources were measured by
      the Copenhagen Psychosocial Questionnaire, the WFC Scale, the Brief Resilient
      Coping Scale and the Questionnaire for Self-efficacy, Optimism and Pessimism.
      Descriptive, correlation and linear regression analyses were applied. RESULTS:
      Clinical doctors working in German hospitals perceived high levels of WFC
      (mean=76). Sociodemographic differences were found for age, marital status and
      presence of children with regard to WFC. No significant gender differences were
      found. WFCs were positively related to high workloads and quantitative job
      demands. Job resources (eg, influence at work, social support) and personal
      resources (eg, resilient coping behaviour and self-efficacy) were negatively
      associated with physicians' WFCs. Interaction terms suggest that job and personal
      resources buffer the effects of job demands on WFC. CONCLUSIONS: In this study,
      WFC was prevalent among German clinicians. Factors of work organisation as well
      as factors of interpersonal relations at work were identified as significant
      predictors for WFC. Our results give a strong indication that both individual and
      organisational factors are related to WFC. Results may play an important role in
      optimising clinical care. Practical implications for physicians' career planning
      and recommendations for future research are discussed.

PMID- 25941178
TI  - Acute Care QUAliTy in chronic Kidney disease (ACQUATIK): a prospective cohort
      study exploring outcomes of patients with chronic kidney disease.
AB  - INTRODUCTION: Chronic kidney disease (CKD) is common and carries a high risk of
      morbidity, including hospital admissions and readmissions and mortality. This is
      largely attributed to an increased risk of cardiovascular disease. Patients with
      CKD are less likely to receive evidence-based treatments for cardiovascular
      disease. However, these treatments are based on trials which generally exclude
      patients with CKD. It is therefore unclear whether this patient group derives the
      same benefits without an increased risk of adverse effects. METHODS AND ANALYSIS:
      The Acute Care QUAliTy in chronic Kidney disease (ACQUATIK) study is a
      prospective, observational, multicentre cohort study. Over 4000 patients will be
      recruited with an enrolment period of 2 years and a follow-up period of 2-4
      years. Patients under follow-up by a renal team will be excluded. Data will be
      obtained from patient and hospital records during the index admission.
      Preadmission data will be extracted from general practice records based on the
      Quality and Outcomes Framework. Diagnosis, comorbidities and procedure data
      pertaining to the index and subsequent admissions will be extracted from the
      Hospital Episode Statistics database and long-term mortality data will be tracked
      using the Office of National Statistics. This information will allow us to
      examine a complete patient journey through primary and secondary care, providing
      unequalled levels of information on treatment and outcomes of patients with CKD.
      The combined data set will be used to compare outcomes and treatments among
      patients with CKD versus patients without CKD. The primary end point is hospital
      readmission rates. The relationship between age, sex, ethnicity, socioeconomic
      status and concurrent comorbidities will be analysed to determine their influence
      on outcomes and treatments. ETHICS AND DISSEMINATION: The ACQUATIK study has been
      approved by the NRES Committee West Midlands-South Birmingham-Reference
      13/WM/0317. The results from ACQUATIK will be submitted for publication in peer
      reviewed journals and presented at primary and secondary care conferences. TRIAL
      REGISTRATION NUMBER: ISRCTN37237454.

PMID- 25941179
TI  - Body mass index in school-aged children and the risk of routinely diagnosed non
      alcoholic fatty liver disease in adulthood: a prospective study based on the
      Copenhagen School Health Records Register.
AB  - OBJECTIVE: The relation between childhood overweight and adult non-alcoholic
      fatty liver disease (NAFLD) is largely unknown. We investigated if weight and
      weight gain in childhood increases the risk of being diagnosed with NAFLD in
      routine clinical settings in adulthood. PARTICIPANTS: We studied 244,464 boys and
      girls, born between 1930 and 1989, who attended school in Copenhagen, Denmark.
      Their heights and weights were measured by physicians or nurses at mandatory
      school health examinations at ages 7-13 years. Body mass index (BMI) z-scores
      were calculated from an internal age-specific and sex-specific reference. OUTCOME
      MEASURES: NAFLD reported in the National Patient Register and the National
      Register of Pathology at 18 years of age or older. HRs with 95% CIs were
      estimated. RESULTS: During follow-up, 1264 and 1106 NAFLD cases, respectively,
      occurred in men and women. In both sexes, childhood BMI z-score was not
      consistently associated with adult NAFLD. Change in BMI z-score between 7 and 13
      years of age was positively associated with NAFLD in both sexes. When adjusted
      for BMI z-score at age 7 years, the HRs of adult NAFLD were 1.15 (95% CI 1.05 to
      1.26) and 1.12 (95% CI 1.02 to 1.23) per 1-unit gain in BMI z-score in men and
      women, respectively. Associations were similar when adjusted for BMI z-score at
      age 13 years, and were consistent across birth years. CONCLUSIONS: A BMI gain in
      school-aged children is associated with adult NAFLD. Intriguingly, BMI gain
      appears to have an effect on adult NAFLD irrespective of either the initial or
      the attained BMI. Taken together, our results suggest that BMI gain in childhood,
      rather than the level of BMI per se, is important in the development of adult
      NAFLD.

PMID- 25941180
TI  - Local food environment interventions to improve healthy food choice in adults: a
      systematic review and realist synthesis protocol.
AB  - INTRODUCTION: Local food environments have been linked with dietary intake and
      obesity in adults. However, overall evidence remains mixed with calls for
      increased theoretical and conceptual clarity related to how availability of
      neighbourhood food outlets, and within-outlet food options, influence food
      purchasing and consumption. The purpose of this work is to develop a programme
      theory of food availability, supported by empirical evidence from a range of
      local food environment interventions. METHODS AND ANALYSIS: A systematic search
      of the literature will be followed by duplicate screening and quality assessment
      (using the Effective Public Health Practice Project tool). Realist synthesis will
      then be conducted according to the Realist And Meta-narrative Evidence Syntheses:
      Evolving Standards (RAMESES) publication standards, including transparent
      appraisal, synthesis and drawing conclusions via consensus. DISSEMINATION: The
      final synthesis will propose an evidence-based programme theory of food
      availability, including evidence mapping to demonstrate contextual factors,
      pathways of influence and potential mechanisms. With the paucity of empirically
      supported programme theories used in current local food environment interventions
      to improve food availability, this synthesis may be used to understand how and
      why interventions work, and thus inform the development of theory-driven,
      evidence-based interventions to improve healthy food choice and future empirical
      work. TRIAL REGISTRATION NUMBER: PROSPERO CRD42014009808.

PMID- 25941181
TI  - Subacute complications during recovery from severe traumatic brain injury:
      frequency and associations with outcome.
AB  - BACKGROUND: Medical complications after severe traumatic brain injury (S-TBI) may
      delay or prevent transfer to rehabilitation units and impact on long-term
      outcome. OBJECTIVE: Mapping of medical complications in the subacute period after
      S-TBI and the impact of these complications on 1-year outcome to inform
      healthcare planning and discussion of prognosis with relatives. SETTING:
      Prospective multicentre observational study. Recruitment from 6 neurosurgical
      centres in Sweden and Iceland. PARTICIPANTS AND ASSESSMENTS: Patients aged 18-65
      years with S-TBI and acute Glasgow Coma Scale 3-8, who were admitted to
      neurointensive care. Assessment of medical complications 3 weeks and 3 months
      after injury. Follow-up to 1 year. 114 patients recruited with follow-up at 1
      year as follows: 100 assessed, 7 dead and 7 dropped out. OUTCOME MEASURE: Glasgow
      Outcome Scale Extended. RESULTS: 68 patients had >=1 complication 3 weeks after
      injury. 3 weeks after injury, factors associated with unfavourable outcome at 1
      year were: tracheostomy, assisted ventilation, on-going infection, epilepsy and
      nutrition via nasogastric tube or percutaneous endoscopic gastroscopy (PEG) tube
      (univariate logistic regression analyses). Multivariate analysis demonstrated
      that tracheostomy and epilepsy retained significance even after incorporating
      acute injury severity into the model. 3 months after injury, factors associated
      with unfavourable outcome were tracheostomy and heterotopic ossification
      (Fisher's test), infection, hydrocephalus, autonomic instability, PEG feeding and
      weight loss (univariate logistic regression). PEG feeding and weight loss at 3
      months were retained in a multivariate model. CONCLUSIONS: Subacute complications
      occurred in two-thirds of patients. Presence of a tracheostomy or epilepsy at 3
      weeks, and of PEG feeding and weight loss at 3 months, had robust associations
      with unfavourable outcome that were incompletely explained by acute injury
      severity.

PMID- 25941182
TI  - Development and validation of a socioculturally competent trust in physician
      scale for a developing country setting.
AB  - Trust in physicians is the unwritten covenant between the patient and the
      physician that the physician will do what is in the best interest of the patient.
      This forms the undercurrent of all healthcare relationships. Several scales exist
      for assessment of trust in physicians in developed healthcare settings, but to
      our knowledge none of these have been developed in a developing country context.
      OBJECTIVES: To develop and validate a new trust in physician scale for a
      developing country setting. METHODS: Dimensions of trust in physicians, which
      were identified in a previous qualitative study in the same setting, were used to
      develop a scale. This scale was administered among 616 adults selected from urban
      and rural areas of Tamil Nadu, south India, using a multistage sampling cross
      sectional survey method. The individual items were analysed using a classical
      test approach as well as item response theory. Cronbach's alpha was calculated
      and the item to total correlation of each item was assessed. After testing for
      unidimensionality and absence of local dependence, a 2 parameter logistic
      Semajima's graded response model was fit and item characteristics assessed.
      RESULTS: Competence, assurance of treatment, respect for the physician and
      loyalty to the physician were important dimensions of trust. A total of 31 items
      were developed using these dimensions. Of these, 22 were selected for final
      analysis. The Cronbach's alpha was 0.928. The item to total correlations were
      acceptable for all the 22 items. The item response analysis revealed good item
      characteristic curves and item information for all the items. Based on the item
      parameters and item information, a final 12 item scale was developed. The scale
      performs optimally in the low to moderate trust range. CONCLUSIONS: The final 12
      item trust in physician scale has a good construct validity and internal
      consistency.

PMID- 25941183
TI  - Does drinking water influence hospital-admitted sialolithiasis on an
      epidemiological level in Denmark?
AB  - OBJECTIVES: Sialolithiasis, or salivary stones, is not a rare disease of the
      major salivary glands. However, the aetiology and incidence remain largely
      unknown. Since sialoliths are comprised mainly of calcium phosphate salts, we
      hypothesise that drinking water calcium levels and other elements in drinking
      water could play a role in sialolithiasis. Owing to substantial intermunicipality
      differences in drinking water composition, Denmark constitutes a unique
      environment for testing such relations. DESIGN: An epidemiological study based on
      patient data extracted from the National Patient Registry and drinking water data
      from the Geological Survey of Denmark and Greenland retrieved as weighted data on
      all major drinking water constituents for each of the 3364 waterworks in Denmark.
      All patient cases with International Statistical Classification of Diseases 10th
      Revision (ICD-10) codes for sialolithiasis registered between the years 2000 and
      2010 were included in the study (n=3014) and related to the drinking water
      composition on a municipality level (n=98). PRIMARY AND SECONDARY OUTCOME
      MEASURES: Multiple regression analysis using iterative search and testing among
      all demographic and drinking water variables with sialolithiasis incidence as the
      outcome in search of possible relations among the variables tested. RESULTS: The
      nationwide incidence of hospital-admitted sialolithiasis was 5.5 cases per
      100,000 citizens per year in Denmark. Strong relations were found between the
      incidence of sialolithiasis and the drinking water concentration of calcium,
      magnesium and hydrogen carbonate, however, in separate models (p<0.001). Analyses
      also confirmed correlations between drinking water calcium and magnesium and
      their concentration in saliva whereas this was not the case for hydrogen
      carbonate. CONCLUSIONS: Differences in drinking water calcium and magnesium may
      play a role in the incidence of sialolithiasis. These findings are of interest
      because many countries have started large-scale desalination programmes of
      drinking water.

PMID- 25941184
TI  - Disparities in the receipt of robot-assisted radical prostatectomy: between
      hospital and within-hospital analysis using 2009-2011 California inpatient data.
AB  - OBJECTIVES: Despite the rapid proliferation of robot-assisted radical
      prostatectomy (RARP), little attention has been paid to patient utilisation of
      this newest surgical innovation and barriers that may result in disparities in
      access to RARP. The goal of this study is to identify demographic and economic
      factors that decrease the likelihood of patients with prostate cancer (PC)
      receiving RARP. DESIGN, SETTING AND PARTICIPANTS: A retrospective, pooled, cross
      sectional study was conducted using 2009-2011 California State Inpatient Data and
      American Hospital Association data. Patients who were diagnosed with PC and
      underwent radical prostatectomy (RP) from 225 hospitals in California were
      identified, using ICD-9-CM diagnosis and procedure codes. PRIMARY OUTCOME
      MEASURES: Patients' likelihood of receiving RARP was associated with patient and
      hospital characteristics using the two models: (1) between-hospital and (2)
      within-hospital models. Multivariate binomial logistic regression was used for
      both models. The first model predicted patient access to RARP-performing
      hospitals versus non-RARP-performing hospitals, after adjusting for patient and
      hospital-level covariates (between-hospital variation). The second model examined
      the likelihood of patients receiving RARP within RARP-performing hospitals
      (within-hospital variation). RESULTS: Among 20,411 patients who received RP,
      13,750 (67.4%) received RARP, while 6661 (32.6%) received non-RARP. This study
      found significant differences in access to RARP-performing hospitals when
      race/ethnicity, income and insurance status were compared, after controlling for
      selected confounding factors (all p<0.001). For example, Hispanic, Medicare and
      Medicaid patients were more likely to be treated at non-RARP-performing hospitals
      versus RARP-performing hospitals. Within RARP-performing hospitals, Medicaid
      patients had 58% lower odds of receiving RARP versus non-RARP (adjusted OR 0.42,
      p<0.001). However, there were no significant differences by race/ethnicity or
      income within RARP-performing hospitals. CONCLUSIONS: Significant differences
      exist by race/ethnicity and payer status in accessing RARP-performing hospitals.
      Furthermore, payer status continues to be an important predictor of receiving
      RARP within RARP-performing hospitals.

PMID- 25941185
TI  - Direct targeting of risk factors significantly increases the detection of liver
      cirrhosis in primary care: a cross-sectional diagnostic study utilising transient
      elastography.
AB  - OBJECTIVES: To assess the feasibility of a novel diagnostic algorithm targeting
      patients with risk factors for chronic liver disease in a community setting.
      DESIGN: Prospective cross-sectional study. SETTING: Two primary care practices
      (adult patient population 10,479) in Nottingham, UK. PARTICIPANTS: Adult patients
      (aged 18 years or over) fulfilling one or more selected risk factors for
      developing chronic liver disease: (1) hazardous alcohol use, (2) type 2 diabetes
      or (3) persistently elevated alanine aminotransferase (ALT) liver function enzyme
      with negative serology. INTERVENTIONS: A serial biomarker algorithm, using a
      simple blood-based marker (aspartate aminotransferase:ALT ratio for hazardous
      alcohol users, BARD score for other risk groups) and subsequently liver stiffness
      measurement using transient elastography (TE). MAIN OUTCOME MEASURES: Diagnosis
      of clinically significant liver disease (defined as liver stiffness >=8 kPa);
      definitive diagnosis of liver cirrhosis. RESULTS: We identified 920 patients with
      the defined risk factors of whom 504 patients agreed to undergo investigation. A
      normal blood biomarker was found in 62 patients (12.3%) who required no further
      investigation. Subsequently, 378 patients agreed to undergo TE, of whom 98 (26.8%
      of valid scans) had elevated liver stiffness. Importantly, 71/98 (72.4%) patients
      with elevated liver stiffness had normal liver enzymes and would be missed by
      traditional investigation algorithms. We identified 11 new patients with definite
      cirrhosis, representing a 140% increase in the number of diagnosed cases in this
      population. CONCLUSIONS: A non-invasive liver investigation algorithm based in a
      community setting is feasible to implement. Targeting risk factors using a non
      invasive biomarker approach identified a substantial number of patients with
      previously undetected cirrhosis. TRIAL REGISTRATION NUMBER: The diagnostic
      algorithm utilised for this study can be found on clinicaltrials.gov
      (NCT02037867), and is part of a continuing longitudinal cohort study.

PMID- 25941186
TI  - Neighbourhood environment, sitting time and motorised transport in older adults:
      a cross-sectional study in Hong Kong.
AB  - OBJECTIVES: Sitting time is a public health concern. This study examined
      associations of objectively measured neighbourhood environmental attributes with
      non-transport sitting time and motorised transport in 484 Hong Kong older adults.
      Neighbourhood attributes encouraging walking may help older adults replace some
      sitting time at home and on motorised transport with light-to-moderate-intensity
      activities such as strolling around the neighbourhood or walking to/from
      neighbourhood destinations. Thus, we hypothesised environmental attributes found
      to be related to walking would show associations with non-transport sitting time
      and motorised transport opposite to those seen for walking. DESIGN: Cross
      sectional. SETTING: Hong Kong, an ultradense urban environment. PARTICIPANTS: 484
      ethnic Chinese Hong Kong residents aged 65+ recruited from membership lists of
      four Hong Kong Elderly Health Centres representing catchment areas of low and
      high transport-related walkability stratified by socioeconomic status (response
      rate: 78%). PRIMARY AND SECONDARY OUTCOME MEASURES: Attributes of participants'
      neighbourhood environments were assessed by environmental audits, while non
      transport sitting time and motorised transport were ascertained using the
      International Physical Activity Questionnaire-Long Form (Chinese version).
      RESULTS: Daily non-transport sitting minutes were 283 (SD=128) and motorised
      transport 23 (SD=28). Prevalence of signs of crime/disorder, streetlights, public
      facilities (toilets and benches) and pedestrian safety were independently
      negatively related, and sloping streets positively related, to sitting outcomes.
      Places of worship in the neighbourhood were predictive of more, and prevalence of
      public transit points of less, non-transport sitting. Associations of either or
      both sitting outcomes with prevalence of food/grocery stores and presence of
      parks were moderated by path obstructions and signs of crime/disorder.
      CONCLUSIONS: The findings suggest that access to specific destinations and
      relatively low-cost, minimal impact modifications to the urban form, such as
      street lighting, public toilets, benches and public transit points, could
      potentially reduce sitting time and associated negative health outcomes in Hong
      Kong older adults.

PMID- 25941188
TI  - Anti-VEGF therapies in the treatment of choroidal neovascularisation secondary to
      non-age-related macular degeneration: a systematic review.
AB  - OBJECTIVES: The aim of this study is to systematically review the evidence for
      anti-vascular endothelial growth factor (VEGF) therapy in choroidal
      neovascularisation secondary to conditions other than age-related macular
      degeneration. DATA SOURCES: MEDLINE, MEDLINE in-process, EMBASE and CENTRAL
      databases and conference abstracts were searched (from inception to Jan 2014).
      STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS: Randomised and non
      randomised comparative studies with follow-up of at least 6 months were included
      and were used to assess clinical effectiveness. STUDY APPRAISAL AND SYNTHESIS
      METHOD: Risk of bias was assessed using the Cochrane risk of bias tool and
      modified Newcastle-Ottawa Scale. Meta-analysis was not possible due to
      methodological heterogeneity. RESULTS: 16 studies met the inclusion criteria
      (1091 eyes; 963 pathological myopia, 74 other conditions). There was large
      variation in risk of bias across studies. An improvement in best-corrected visual
      acuity in anti-VEGF arms over comparators was reported in all studies. The
      proportion of patients improving by at least 15 letters in anti-VEGF arms ranged
      from 27.3% to 70%. There were no significant differences between bevacizumab and
      ranibizumab. LIMITATIONS: Owing to the rarity of choroidal neovascularisation
      secondary to conditions other than age-related macular degeneration or
      pathological myopia, there are unlikely to ever be sufficiently powered trials in
      these populations. CONCLUSIONS: Bevacizumab and ranibizumab appear to be
      effective in improving visual acuity for patients with choroidal
      neovascularisation secondary to conditions other than age-related macular
      degeneration. The evidence base is strongest for choroidal neovascularisation
      secondary to pathological myopia, however, based on current evidence and likely
      pharmacological pathways, clinicians should consider treatment with either
      bevacizumab or ranibizumab for rarer causes.

PMID- 25941189
TI  - How does acupuncture affect insulin sensitivity in women with polycystic ovary
      syndrome and insulin resistance? Study protocol of a prospective pilot study.
AB  - INTRODUCTION: Hyperinsulinaemia and insulin resistance (IR) are key features of
      polycystic ovary syndrome (PCOS) and metabolic syndrome. The effect of 5 weeks of
      acupuncture treatment has been investigated in a completed prospective pilot
      trial (Clinicaltrials.gov: NCT01457209), and acupuncture with electrical
      stimulation applied to insulin-resistant rats with dihydrotestosterone-induced
      PCOS was shown to improve insulin sensitivity. Therefore, we now aim to conduct a
      prospective pilot study to evaluate whether using the same acupuncture treatment
      protocol given over a longer period of time (6 months) than in the previous pilot
      trial will improve insulin sensitivity in women with PCOS and IR. Our hypothesis
      is that acupuncture with combined manual and low-frequency electrical stimulation
      of the needles will improve insulin sensitivity in women with PCOS and IR.
      METHODS/ANALYSIS: This is a prospective pilot trial. A total of 112 women with
      PCOS and IR will be recruited and categorised according to their body mass index
      (BMI) as normal weight (BMI=18.5-23 kg/m(2)) or as overweight/obese (BMI>23
      kg/m(2)). Acupuncture will be applied three times per week for 6 months at 30 min
      per treatment. The primary outcome will be the change in insulin sensitivity
      before and after 6 months of acupuncture treatment, as measured by an oral
      glucose tolerance test. ETHICS/DISSEMINATION: Ethical approval of this study has
      been granted from the ethics committee of the First Affiliated Hospital of
      Guangzhou Medical University (No. 2013039). Written and informed consent will be
      obtained from each patient before any study procedure is performed, according to
      good clinical practice. The results of this trial will be disseminated in a peer
      reviewed journal and presented at international congresses. TRIAL REGISTRATION
      NUMBERS: NCT02026323 and ChiCTR-OCH-13003921.

PMID- 25941187
TI  - Diagnosed diabetes and premature death among middle-aged Japanese: results from a
      large-scale population-based cohort study in Japan (JPHC study).
AB  - OBJECTIVE: To examine the association between diabetes and premature death for
      Japanese general people. DESIGN: Prospective cohort study. SETTING: The Japan
      Public Health Center-based prospective study (JPHC study), data collected between
      1990 and 2010. POPULATION: A total of 46,017 men and 53,567 women, aged 40-69
      years at the beginning of baseline survey. MAIN OUTCOME MEASURES: Overall and
      cause specific mortality. Cox proportional hazards models were used to calculate
      the HRs of all cause and cause specific mortality associated with diabetes.
      RESULTS: The median follow-up period was 17.8 years. During the follow-up period,
      8223 men and 4640 women have died. Diabetes was associated with increased risk of
      death (856 men and 345 women; HR 1.60, (95% CI 1.49 to 1.71) for men and 1.98
      (95% CI 1.77 to 2.21) for women). As for the cause of death, diabetes was
      associated with increased risk of death by circulatory diseases (HR 1.76 (95% CI
      1.53 to 2.02) for men and 2.49 (95% CI 2.06 to 3.01) for women) while its
      association with the risk of cancer death was moderate (HR 1.25 (95% CI 1.11 to
      1.42) for men and 1.04 (95% CI 0.82 to 1.32) for women). Diabetes was also
      associated with increased risk of death for 'non-cancer, non-circulatory system
      disease' (HR 1.91 (95% CI 1.71 to 2.14) for men and 2.67 (95% CI 2.25 to 3.17)
      for women). CONCLUSIONS: Diabetes was associated with increased risk of death,
      especially the risk of death by circulatory diseases.

PMID- 25941190
TI  - The feasibility of using manual segmentation in a multifeature computer-aided
      diagnosis system for classification of skin lesions: a retrospective comparative
      study.
AB  - OBJECTIVES: To investigate the feasibility of manual segmentation by users of
      different backgrounds in a previously developed multifeature computer-aided
      diagnosis (CADx) system to classify melanocytic and non-melanocytic skin lesions
      based on conventional digital photographic images. METHODS: In total, 347
      conventional photographs of melanocytic and non-melanocytic skin lesions were
      retrospectively reviewed, and manually segmented by two groups of physicians,
      dermatologists and general practitioners, as well as by an automated segmentation
      software program, JSEG. The performance of CADx based on inputs from these two
      groups of physicians and that of the JSEG program was compared using feature
      agreement analysis. RESULTS: The estimated area under the receiver operating
      characteristic curve for classification of benign or malignant skin lesions based
      were comparable on individual segmentation by the gold standard (0.893, 95% CI
      0.856 to 0.930), dermatologists (0.886, 95% CI 0.863 to 0.908), general
      practitioners (0.883, 95% CI 0.864 to 0.903) and JSEG (0.856, 95% CI 0.812 to
      0.899). The agreement in the malignancy probability scores among the physicians
      was excellent (intraclass correlation coefficient: 0.91). By selecting an optimal
      cut-off value of malignancy probability score, the sensitivity and specificity
      were 80.07% and 81.47% for dermatologists and 79.90% and 80.20% for general
      practitioners. CONCLUSIONS: This study suggests that manual segmentation by
      general practitioners is feasible in the described CADx system for classifying
      benign and malignant skin lesions.

PMID- 25941191
TI  - A retrospective cohort study to investigate fatigue, psychological or cognitive
      impairment after TIA: protocol paper.
AB  - INTRODUCTION: Transient ischaemic attack (TIA) is defined by short-lasting,
      stroke-like symptoms, and is recognised as a medical emergency. Symptoms are
      assumed to completely resolve, and treatment is focused on secondary stroke/TIA
      prevention. However, evidence suggests that patients with TIA may experience
      ongoing residual impairments, which they do not receive therapy for as standard
      practice. TIA-induced sequelae could impact on patients' quality of life and
      ability to return to work or social activities. We aim to investigate whether TIA
      is associated with subsequent consultation for fatigue, psychological or
      cognitive impairment in primary care. METHODS AND ANALYSIS: A retrospective open
      cohort study of patients with first-ever TIA and matched controls. Relevant data
      will be extracted from The Health Improvement Network (THIN) database, an
      anonymised primary care database which includes data for over 12 million patients
      and covers approximately 6% of the UK population. Outcomes will be the first
      consultation for fatigue, anxiety, depression, post-traumatic stress disorder or
      cognitive impairment. Principal analysis will use Kaplan-Meier survivor functions
      to estimate time to first consultation, with log-rank tests to compare TIA and
      control patients. Cox proportional hazard models will predict the effect of
      demographic and patient characteristics on time to first consultation. ETHICS AND
      DISSEMINATION: Approval was granted by a THIN Scientific Review Committee (ref:
      14-008). The study's findings will be published in a peer-reviewed journal and
      disseminated at national and international conferences and through social media.

PMID- 25941192
TI  - Does diabetes self-management education in conjunction with primary care improve
      glycemic control in Hispanic patients? A systematic review and meta-analysis.
AB  - PURPOSE: The purpose of this systematic review and meta-analysis is to evaluate
      the effectiveness of diabetes self-management education (DSME) interventions
      delivered in conjunction with primary care among Hispanic adults with type 2
      diabetes mellitus (T2DM). METHODS: A systematic search of PubMed, Cochrane
      Library, and the Cumulative Index to Nursing and Allied Health Literature
      identified randomized controlled trials (RCT) that tested the effect of DSME
      interventions in Hispanic adults with T2DM. Studies reporting hemoglobin A1C
      (A1C) pre and post intervention or change in A1C were eligible for inclusion in
      the meta-analysis. RESULTS: Of 625 studies identified, 13 RCTs met criteria for
      inclusion in the systematic review; of these, 11 studies were included in the
      meta-analysis. The 13 RCTs represent data from 2784 adult Hispanic subjects. DSME
      interventions (individual, group, telephone/electronic, and multimodal sessions)
      varied in intensity from 1-time DSME sessions with phone follow-up to contact
      every 4 to 6 weeks over 5 years. At >=6 months following intervention, pooled A1C
      reduction was -0.25 (95% CI, -0.42 to -0.07), favoring the intervention group.
      CONCLUSIONS: DSME in conjunction with primary care is effective in improving
      glycemic control in Hispanic adults with T2DM. Future comparative effectiveness
      research is needed to identify best delivery methods to optimize effectiveness of
      DSME delivered to the Hispanic population.

PMID- 25941195
TI  - Mortality in the Elderly on Dialysis: Is This the Right Debate?

PMID- 25941193
TI  - Cytokines: Names and Numbers You Should Care About.
AB  - Cytokines play an important role in host defense against microorganisms. They
      orchestrate innate immunity by inducing protective local inflammation and
      systemic acute phase responses. Cytokines are important in initiating,
      amplifying, directing, mediating, and regulating adaptive immunity.
      Unfortunately, they may also direct tissue damage if excessive responses occur or
      if they are involved in directing and mediating autoimmunity. Under these
      circumstances, cytokines are potential therapeutic targets. Over the last 20
      years, we have seen the successful development and clinical implementation of
      biologic strategies that target key cytokines in specific inflammatory diseases
      with efficacy, specificity, and toxicity profiles challenging conventional drug
      therapies. These therapies are finding new applications and many new agents show
      promise. Unfortunately, these new cytokine-based therapies have had little effect
      on renal disease. This review provides evidence that common renal diseases,
      including those causing AKI and the autoimmune proliferative and crescentic forms
      of GN, have cytokine mediation profiles that suggest they would be susceptible to
      cytokine-targeting therapeutic strategies. 

PMID- 25941196
TI  - Radiographic Outcomes of Preoperative CT Scan-Derived Patient-Specific Total
      Ankle Arthroplasty.
AB  - BACKGROUND: Preoperative computer navigation and patient-specific instrumentation
      have had promising results in total knee arthroplasty and in a previous cadaveric
      total ankle arthroplasty (TAA) study. Potential benefits of patient-specific
      guides include improved implant alignment and decreased surgical time. The
      purpose of this retrospective case series was to evaluate the accuracy,
      reproducibility, and limitations of TAA tibia and talar implant placement and
      radiographic alignment using preoperative computed tomography (CT) scan-derived
      instrumentation in a clinical setting. METHODS: Between 2012 and 2014, 42
      consecutive TAA cases in 42 patients using preoperative CT scan-derived patient
      specific plans and guides (PROPHECY, Wright Medical Technology, Memphis TN) were
      reviewed from a single center of foot and ankle fellowship-trained orthopaedic
      surgeons. TAA implants used included 29 intramedullary referencing implants
      (INBONE II, Wright Medical Technology) and 13 low-profile tibia and talar
      resurfacing implants (Infinity, Wright Medical Technology). All patients had
      standardized preoperative CT scans before surgery that were used to create custom
      surgical plans and 3-dimensional solid cutting guides and models. All patients
      had a minimum 3-month follow-up with weightbearing postoperative radiographs.
      Patient demographics were recorded, and coronal and sagittal alignments were
      compared among weightbearing preoperative radiographs, CT scan-derived surgical
      plans, and weightbearing postoperative radiographs using a digital picture
      archiving and communication system. RESULTS: Average age for all patients was 63
      +/- 9 years, with a body mass index of 29.8 +/- 5.9. Average total surgical time
      for all TAAs was 100 +/- 11 minutes, with Infinity TAAs taking less time than
      INBONE II TAAs (92 vs 104 minutes; P < .05). Average preoperative coronal
      alignment was 1.9 degrees varus +/- 6.4 (range, 14 degrees valgus to 10 degrees
      varus). Postoperative weightbearing alignments for all TAA cases were within +/-3
      degrees  of the predicted coronal and sagittal alignments from the CT scan
      derived surgical plans. There were no significant differences in pre- or
      postoperative weightbearing alignments between INBONE II and Infinity TAA cases.
      Neutral coronal and sagittal alignments were obtained for all TAA cases
      regardless of preoperative deformity. Patient-specific surgical plans were
      accurate to within 1 size for tibia and talar implants used. Surgical plans
      predicted the actual tibia implant size used in 100% of INBONE II cases and 92%
      of Infinity cases. Plans were less accurate for talar implants and predicted the
      actual talar implant size used in 76% of INBONE II cases and 46% of Infinity
      cases. In all cases of predicted tibia or talar size mismatch, surgical plans
      predicted 1 implant size larger than actually used. CONCLUSIONS: Results from
      this study provide early clinical evidence that preoperative CT scan-derived
      patient-specific surgical plans and guides can help provide accurate and
      reproducible TAA radiographic alignments. Talar implant sizing was not as
      accurate due to individual surgeon preference regarding the extent of gutter
      debridement. Similar to other modern computer navigation and patient-specific
      instrumentation systems, final coronal and sagittal alignments were within 3
      degrees of the predicted surgical plans, and sizing was accurate within 1 implant
      size. Future studies are warranted to investigate the clinical and functional
      implications of patient-specific TAA and the overall cost-effectiveness of this
      technique. LEVEL OF EVIDENCE: Level IV, retrospective case series.

PMID- 25941194
TI  - Dialysis Modality and Mortality in the Elderly: A Meta-Analysis.
AB  - BACKGROUND AND OBJECTIVES: Identifying the appropriate choice between
      hemodialysis (HD) and peritoneal dialysis (PD) is an unresolved issue in elderly
      patients with ESRD, who are at high risk for death but have a low chance of
      receiving kidney transplantation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:
      Data on 13,065 incident dialysis Korean patients (age>=65 years) receiving HD
      (n=10,675) or PD (n=2390) were obtained from the Korean Health Insurance dataset.
      Multiple statistical approaches, including the multivariate Cox model, were used
      to compare mortality between Korean patients receiving PD and those receiving HD.
      Subsequently, meta-analysis of previous comparison studies (published since the
      year 2000; population-based studies) and the Korean dataset was performed.
      RESULTS: During a mean duration of 1.8+/-1.3 years (maximum of 5 years), the
      Korean PD group had a higher mortality rate than the Korean HD group (hazard
      ratio [HR], 1.20 [95% confidence interval (95% CI), 1.13 to 1.28]; P<0.001 by
      multivariate Cox model). The discrepancy between the two modalities was greater
      in the presence of certain conditions, such as diabetes mellitus or longer
      dialysis duration. In the meta-analysis, 15 studies involving >631,421 elderly
      patients were reviewed. Compared with HD, the pooled HR with PD was 1.10 (95% CI,
      1.01 to 1.20). When the meta-analysis was stratified by confounding factors, the
      survival benefit from HD was particularly strong in subgroups that had diabetes
      mellitus, had long dialysis duration (>1 year), or contained cohorts starting
      dialysis in the 1990s. CONCLUSIONS: A meta-analysis that included results in
      Korean patients suggests a higher risk for death in elderly patients receiving PD
      than in those receiving HD.

PMID- 25941197
TI  - Evaluation of absorbable and nonabsorbable sutures for repair of achilles tendon
      rupture with a suture-guiding device.
AB  - BACKGROUND: The purpose of this study was to compare the functional and clinical
      results of Achilles tendon repairs with an Achilles tendon suture-guiding device
      using nonabsorbable versus absorbable sutures. We hypothesized that the
      absorbable suture would have clinical results comparable to those of the
      nonabsorbable suture for Achilles tendon repair with an Achilles tendon suture
      guiding system. METHODS: From January 2010 to September 2013, 48 consecutive
      patients who had sustained a spontaneous rupture of the Achilles tendon underwent
      operative repair with an Achilles tendon suture-guiding device using 2 different
      suture types. All ruptures were acute. The patients were divided equally into 2
      groups according to suture type. In the nonabsorbable suture group, No. 2 braided
      nonabsorbable polyethylene terephthalate sutures were used, and in the absorbable
      suture group, braided absorbable polyglactin sutures were used. The average age
      of the patients was 38 years (range, 28-50 years). Functional outcome scores and
      complications were evaluated. RESULTS: All patients had an intact Achilles repair
      after surgery. The American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot
      clinical outcome scores were 98 (range, 90-100) in the nonabsorbable suture group
      and 96.8 (range, 87-100) in the absorbable suture group. All patients returned to
      their previous work. The absorbable suture group had fewer postoperative
      complications (0%) than the nonabsorbable suture group (12.5%) (P < .05).
      CONCLUSION: Use of an absorbable suture in the treatment of Achilles tendon
      repair by an Achilles tendon suture-guiding system was associated with a lower
      incidence of suture reaction; however, functionally the results were not notably
      different from those using a traditional nonabsorbable suture. We conclude that
      repair with absorbable sutures is appropriate for Achilles tendon ruptures. LEVEL
      OF EVIDENCE: Level II, prospective comparative study.

PMID- 25941198
TI  - Validation of the MD Anderson Symptom Inventory-Head-and-Neck-Filipino (MDASI-HN
      F): clinical utility of symptom screening among patients with head-and-neck
      cancer.
AB  - CONTEXT: Symptom burden and quality of life (QOL) are of particular importance in
      head-and-neck cancer treatment. The MD Anderson Symptom Inventory-Head-and-Neck
      (MDASI-HN) is a simple symptom assessment tool practicable for patient follow-up,
      but a validated Filipino translation was previously unavailable. OBJECTIVES: The
      objectives of this study were to develop a valid Filipino translation of the
      MDASI-HN, to test the sensitivity of the validated MDASI core-F, and to report
      the prevalence and pattern of head-and-neck symptoms in our cohort. METHODS: An
      MDASI-HN-Filipino (MDASI-HN-F) version was developed and examined for convergent
      validity, internal consistency, test-retest reliability, known-group validity and
      sensitivity to change. Eligible participants were aged 18-80 years, with
      histopathologically-proven head-and-neck (except thyroid) cancer, able to
      understand and read English and Filipino, and without cognitive impairment or
      other conditions precluding self-administration of the questionnaire. RESULTS:
      Participants (n=100) were aged 18-76 years; the majority were aged <60, male,
      married, had college schooling, or were from a Tagalog-speaking region. The
      validity of the MDASI HN-F was demonstrated in all parameters. Age or educational
      attainment did not affect convergent validity or test-retest reliability. At
      baseline, 48% had multiple moderate/severe symptoms and 38% had at least one
      severe symptom. CONCLUSIONS: The MDASI-HN-F is valid, reliable and sensitive. The
      sensitivity of the MDASI core-F is demonstrated, and its validity and reliability
      reaffirmed. Moderate and severe head-and-neck symptoms are prevalent in early
      stage and advanced-stage head-and-neck cancers, reflecting the utility of symptom
      screening for improvement of symptom management, QOL and compliance to treatment.

PMID- 25941199
TI  - Twisted steel-induced penetrating head injury.

PMID- 25941200
TI  - Why brain death is considered death and why there should be no confusion.

PMID- 25941202
TI  - SPG7 mutations are a common cause of undiagnosed ataxia.

PMID- 25941201
TI  - Clinical and ethical judgment: A profound dilemma.

PMID- 25941203
TI  - Vigabatrin retinal toxicity in children with infantile spasms: An observational
      cohort study.

PMID- 25941204
TI  - Pearls & Oysters: A case of refractory nocturnal seizures: Putting out fires
      without smoke.

PMID- 25941205
TI  - Teaching NeuroImages: Cockayne syndrome with extensive intracranial
      calcification.

PMID- 25941206
TI  - Teaching NeuroImages: MRI findings in carbamoyl phosphate synthetase 1
      deficiency.

PMID- 25941208
TI  - Calcaneal Insufficiency Fracture Secondary to Celiac Disease-Induced
      Osteomalacia: A Rare Cause of Heel Pain.
AB  - Plantar fasciitis is a common cause of plantar heel pain; however, a broad
      spectrum of disorders may also present with plantar heel pain. A detailed
      history, physical examination, laboratory testing, and imaging studies may be
      necessary to reach an accurate diagnosis. Herein, the clinical presentation of a
      33-year-old woman with calcaneal insufficiency fracture secondary to celiac
      disease-induced osteomalacia is presented, and its diagnosis and treatment are
      discussed. Calcaneal insufficiency fractures should be kept in mind in a patient
      with celiac disease that presents with heel pain. LEVEL OF EVIDENCE: Therapeutic,
      Level IV: Case study.

PMID- 25941207
TI  - An Adolescent Substance Prevention Model Blocks the Effect of CHRNA5 Genotype on
      Smoking During High School.
AB  - INTRODUCTION: Prevention intervention programs reduce substance use, including
      smoking, but not all individuals respond. We tested whether response to a
      substance use prevention/intervention program varies based upon a set of five
      markers (rs16969968, rs1948, rs578776, rs588765, and rs684513) within the cluster
      of nicotinic acetylcholine receptor subunit genes (CHRNA5/A3/B4). METHODS:
      Participants (N = 424) were randomly assigned to either control condition, or a
      family-based intervention in grade 6 and a school-based drug preventive
      intervention in grade 7. Smoking in the past month was assessed in grades 9-12
      using a four-point scale (0 = never smoked, 1 = smoked but not in last month, 2 =
      one or a few times, 3 = about once a week or more). RESULTS: There was a main
      effect of both the intervention (b = -0.24, P < .05) and genotype at rs16969968
      (b = 0.14, P < .05) on high school smoking. Using dummy coding to allow for
      nonlinear effects, individuals with the A/A genotype smoked more often than those
      with G/G (b = 0.33, P < .05). A genotype * intervention effect was found with
      reduced smoking among those with A/A and G/A genotypes to levels similar to those
      with the G/G genotype (G/G vs. A/A: b = -0.67, P < .05; A/G vs. A/A: b = -0.61, P
      < .05; G/G vs. A/G ns). Results were nonsignificant for the other four markers.
      CONCLUSIONS: Preventive interventions can reduce the genetic risk for smoking
      from rs16969968.

PMID- 25941209
TI  - Allograft Reconstruction of the Lisfranc Ligament.
AB  - For Lisfranc injuries, screw fixation of the medial and middle columns is
      currently the standard of treatment. The purpose of this study was to
      biomechanically evaluate the use of allograft for a severed Lisfranc ligament
      compared to standard screw fixation and the intact condition. Six pairs of fresh
      frozen cadaveric lower extremities were prepared with reflective marker arrays
      and cyclically loaded to simulate partial weight bearing under 4 sequential
      testing conditions: (1) intact ligament, (2) disrupted ligament, (3) tendon
      allograft reconstructed ligament, and (4) rigid screw fixation. The relative
      displacement between the medial cuneiform and the second metatarsal was assessed
      via motion analysis. A mixed model analysis of variance was used to determine the
      significance (alpha = .05) of displacement differences. Mean displacements and
      95% confidence intervals for each condition were as follows: (1) intact 9.1 (7.1
      11.2) mm, (2) cut ligament 9.4 (7.4-11.5) mm, (3) allograft fixation 8.8 (6.8
      10.9) mm, and (4) screw fixation 8.2 (6.2-10.3) mm. There were no significant
      differences among the specimens according to condition. Allograft fixation
      provided adequate strength and stability and did not differ significantly
      compared to intact or screw fixation. LEVELS OF EVIDENCE: Level V: Bench testing.

PMID- 25941210
TI  - Forefoot Deformity in Rheumatoid Arthritis: A Comparison of Shod and Unshod
      Populations.
AB  - All reported rheumatoid arthritis (RA) forefoot deformities in the literature
      thus far have arisen from shoe wearing populations. Our aim in this study was to
      compare hallucal deformities seen in a shod population with an unshod population.
      A population comparison was undertaken in 2 specialized foot and ankle units, one
      in India and one in the United Kingdom. In the shod population, there was 1
      hallux varus deformity, 10 without hallucal deformity, and 90 hallux valgus
      deformities. In contrast, in the unshod population, there were 19 hallux varus
      deformities and 6 hallux valgus deformities. There was great variability in the
      lesser toe deformity seen. In the shod population, it was most common to see
      dorsal subluxation or dislocation, with the fifth toe in a varus position. In the
      unshod population, the most common lesser toe deformity seen was varus deviation
      or dislocation. Instability of the metatarsophalangeal joint in the rheumatoid
      foot predisposes it to significant deformity. In the non-shoe wearing population,
      intrinsic muscle forces and weight bearing forces are the most likely
      determinants of the deformity, with hallux varus being a more common presenting
      problem. In the shod population, the external forces of shoe wear dictate the
      direction of deformity. LEVELS OF EVIDENCE: Prognostic, Level III: Case control
      study.

PMID- 25941211
TI  - Implementation and impact of a post-exposure prophylaxis helpline.
AB  - BACKGROUND: Despite a 2007 national and regional training programme, there was
      poor implementation of a post-exposure prophylaxis (PEP) programme to prevent
      occupational transmission of HIV in health care workers (HCWs) in Delhi. A new
      initiative was therefore launched by the Delhi State AIDS Control Society in 2010
      to improve uptake of PEP in HCWs. AIMS: To assess the implementation and efficacy
      of the PEP programme in Delhi. METHODS: The initiative included a PEP poster and
      a telephone helpline together with a workshop for senior doctors of 46 public
      hospitals nominated as PEP supervisors. Data concerning use of the PEP help line
      and number of HCWs enrolling for PEP between January 2011 and May 2014 were
      analysed. RESULTS: Until September 2010, only 61% (28) of Delhi hospitals had PEP
      drugs and medical supervisors to manage the programme and reports concerning the
      programme were not sent. After roll-out of the PEP helpline, 4057 HCWs accessed
      the helpline, all public hospitals started implementing the programme and sent
      monthly reports. During the same period, 1450 HCWs suffered from occupational
      exposures, 15% were started on PEP drugs of who 98% completed the full course of
      prophylaxis. CONCLUSIONS: The PEP helpline is probably the first in a developing
      country and has been helpful for the effective implementation of the national PEP
      programme in Delhi.

PMID- 25941212
TI  - Development of a convenience and safety chilled sous vide fish dish:
      Diversification of aquacultural products.
AB  - The dynamic expansion of the ready-to-eat seabream sector in its adaptation to
      new lifestyles has led to the search for new presentation formats in seabream
      (Sparus aurata). Green sauce (olive oil, wine vinegar, garlic, fresh parsley,
      black pepper, basil and salt) and 60 C of cooking temperature were chosen by the
      panellists for the sous vide cooking process. Seabream fillet and sauce were
      packaged in polypropylene trays, cooked, chilled and stored at 2 C.
      Microbiological (total viable counts,Enterobacteriaceae,lactic acid bacteria,
      anaerobic psychrotrophic, moulds and yeasts, Salmonella and Listeria
      monocytogenes), chemical (pH and TBARs) and sensory parameters were determined at
      0, 7, 17, 34, 48 and 62 days. In the conditions used, the microbiological counts
      remained stable, and Salmonella and Listeria monocytogenes were absent. The
      acidic sauce had a positive effect on the pH of the product, and low TBARs were
      obtained throughout storage. The processing conditions used in the present study
      allowed a chilled ready-to-eat seabream product of consistently high quality up
      to 62 days of storage to be obtained, representing an expansion of the products
      offered by the aquacultural industry.

PMID- 25941213
TI  - Comment on "A systematic review of the association between pleural plaques and
      changes in lung function" by Kopylev et al (2014).

PMID- 25941214
TI  - Prison Meditation Movements and Mass Incarceration.
AB  - By some estimates, more than half of inmates held in jails and prisons in the
      United States have a substance use disorder. Treatments involving the teaching of
      meditation and other contemplative practices have been developed for a variety of
      physical and mental disorders, including drug and alcohol addiction. At the same
      time, an expanding volunteer movement across the country has been bringing
      meditation and yoga into jails and prisons. This review first examines the
      experimental research on one such approach-mindfulness meditation as a treatment
      for drug and alcohol addiction, as well as the research on mindfulness in
      incarcerated settings. We argue that to make a substantial impact on recidivism,
      such programs must mirror volunteer programs which emphasize interdependency and
      non-duality between the "helper" and the "helped," and the building of meditation
      communities both inside and outside of prison. 

PMID- 25941215
TI  - Inhibition of aminoglycoside acetyltransferase resistance enzymes by metal salts.
AB  - Aminoglycosides (AGs) are clinically relevant antibiotics used to treat
      infections caused by both Gram-negative and Gram-positive bacteria, as well as
      Mycobacteria. As with all current antibacterial agents, resistance to AGs is an
      increasing problem. The most common mechanism of resistance to AGs is the
      presence of AG-modifying enzymes (AMEs) in bacterial cells, with AG
      acetyltransferases (AACs) being the most prevalent. Recently, it was discovered
      that Zn(2+) metal ions displayed an inhibitory effect on the resistance enzyme
      AAC(6')-Ib in Acinetobacter baumannii and Escherichia coli. In this study, we
      explore a wide array of metal salts (Mg(2+), Cr(3+), Cr(6+), Mn(2+), Co(2+),
      Ni(2+), Cu(2+), Zn(2+), Cd(2+), and Au(3+) with different counter ions) and their
      inhibitory effect on a large repertoire of AACs [AAC(2')-Ic, AAC(3)-Ia, AAC(3)
      Ib, AAC(3)-IV, AAC(6')-Ib', AAC(6')-Ie, AAC(6')-IId, and Eis]. In addition, we
      determine the MIC values for amikacin and tobramycin in combination with a zinc
      pyrithione complex in clinical isolates of various bacterial strains (two strains
      of A. baumannii, three of Enterobacter cloacae, and four of Klebsiella
      pneumoniae) and one representative of each species purchased from the American
      Type Culture Collection.

PMID- 25941216
TI  - Sequential combination therapy with pegylated interferon leads to loss of
      hepatitis B surface antigen and hepatitis B e antigen (HBeAg) seroconversion in
      HBeAg-positive chronic hepatitis B patients receiving long-term entecavir
      treatment.
AB  - Nucleos(t)ide analogues rarely result in a durable off-treatment response in
      chronic hepatitis B infection, whereas pegylated interferon (Peg-IFN) induces a
      long-lasting response only in a subset of patients. We assessed the effect of
      sequential combination therapy with Peg-IFN-alpha2a and entecavir in hepatitis B
      e antigen (HBeAg)-positive patients with prior long-term entecavir therapy and
      investigated the predictors of response to treatment. HBeAg-positive individuals
      who did not achieve HBeAg seroconversion during previous long-term entecavir
      therapy, receiving Peg-IFN-alpha2a added to ongoing entecavir therapy (sequential
      combination [S-C] therapy; n = 81) for 48 weeks or remaining on entecavir
      monotherapy (n = 116), were retrospectively included. A matched pair was created
      at a 1:1 ratio from each treatment group. The primary endpoint was HBeAg
      seroconversion at week 48. Subgroup analysis of response prediction was conducted
      for 81 patients with S-C therapy. More patients in the S-C therapy group achieved
      HBeAg seroconversion than those in the entecavir group (44% versus 6%; P <
      0.0001). An HBeAg level of <200 signal-to-cutoff ratio (S/CO) at baseline was a
      strong predictor for higher HBeAg seroconversion than that achieved when HBeAg
      was >=200 S/CO (64.2% versus 17.9%; P < 0.0001). Hepatitis B surface antigen
      (HBsAg) levels at baseline and the decrease in HBsAg levels predicted HBsAg loss
      in the S-C therapy group. The combination of baseline HBeAg of <200 S/CO and
      HBsAg of <1,000 IU/ml and an HBsAg decline at week 12 of >=0.5 log10 IU/ml
      provided the highest rate of HBeAg seroconversion (92.31%) and HBsAg loss (83.3%)
      at week 48. Patients receiving sequential combination therapy have a higher rate
      of HBeAg seroconversion and are more likely to experience HBsAg clearance than do
      those continuing entecavir monotherapy. Sequential combination therapy can be
      guided by baseline HBsAg/HBeAg levels and on-treatment HBsAg dynamics.

PMID- 25941217
TI  - Mutations associated with reduced surotomycin susceptibility in Clostridium
      difficile and Enterococcus species.
AB  - Clostridium difficile infection (CDI) is an urgent public health concern causing
      considerable clinical and economic burdens. CDI can be treated with antibiotics,
      but recurrence of the disease following successful treatment of the initial
      episode often occurs. Surotomycin is a rapidly bactericidal cyclic lipopeptide
      antibiotic that is in clinical trials for CDI treatment and that has demonstrated
      superiority over vancomycin in preventing CDI relapse. Surotomycin is a
      structural analogue of the membrane-active antibiotic daptomycin. Previously, we
      utilized in vitro serial passage experiments to derive C. difficile strains with
      reduced surotomycin susceptibilities. The parent strains used included ATCC
      700057 and clinical isolates from the restriction endonuclease analysis (REA)
      groups BI and K. Serial passage experiments were also performed with vancomycin
      resistant and vancomycin-susceptible Enterococcus faecium and Enterococcus
      faecalis. The goal of this study is to identify mutations associated with reduced
      surotomycin susceptibility in C. difficile and enterococci. Illumina sequence
      data generated for the parent strains and serial passage isolates were compared.
      We identified nonsynonymous mutations in genes coding for cardiolipin synthase in
      C. difficile ATCC 700057, enoyl-(acyl carrier protein) reductase II (FabK) and
      cell division protein FtsH2 in C. difficile REA type BI, and a PadR family
      transcriptional regulator in C. difficile REA type K. Among the 4 enterococcal
      strain pairs, 20 mutations were identified, and those mutations overlap those
      associated with daptomycin resistance. These data give insight into the mechanism
      of action of surotomycin against C. difficile, possible mechanisms for resistance
      emergence during clinical use, and the potential impacts of surotomycin therapy
      on intestinal enterococci.

PMID- 25941218
TI  - Direct administration in the respiratory tract improves efficacy of broadly
      neutralizing anti-influenza virus monoclonal antibodies.
AB  - The emergence of influenza virus strains resistant to approved neuraminidase
      inhibitors and the time constrains after infection when these drugs can be
      effective constitute major drawbacks for this class of drugs. This highlights a
      critical need to discover new therapeutic agents that can be used for the
      treatment of influenza virus-infected patients. The use of broadly neutralizing
      anti-influenza monoclonal antibodies (MAbs) has been sought as an alternative
      immunotherapy against influenza infection. Here, we tested in mice previously
      characterized broadly neutralizing anti-hemagglutinin (HA) stalk MAbs
      prophylactically and therapeutically using different routes of administration.
      The efficacy of treatment against an influenza H1N1 pandemic virus challenge was
      compared between two systemic routes of administration, intraperitoneal (i.p.)
      and intravenous (i.v.), and two local routes, intranasal (i.n.) and aerosol
      (a.e.). The dose of MAb required for prophylactic protection was reduced by 10
      fold in animals treated locally (i.n. or a.e.) compared with those treated
      systemically (i.p. or i.v.). Improved therapeutic protection was observed in
      animals treated i.n. on day 5 postinfection (60% survival) compared with those
      treated via the i.p. route (20% survival). An increase in therapeutic efficacy
      against other influenza virus subtypes (H5N1) was also observed when a local
      route of administration was used. Our findings demonstrate that local
      administration significantly decreases the amount of broadly neutralizing
      monoclonal antibody required for protection against influenza, which highlights
      the potential use of MAbs as a therapeutic agent for influenza-associated
      disease.

PMID- 25941219
TI  - Metronidazole- and carbapenem-resistant bacteroides thetaiotaomicron isolated in
      Rochester, Minnesota, in 2014.
AB  - Emerging antimicrobial resistance in members of the Bacteroides fragilis group is
      a concern in clinical medicine. Although metronidazole and carbapenem resistance
      have been reported in Bacteroides thetaiotaomicron, a member of the B. fragilis
      group, they have not, to the best of our knowledge, been reported together in the
      same B. thetaiotaomicron isolate. Herein, we report isolation of piperacillin
      tazobactam-, metronidazole-, clindamycin-, ertapenem-, and meropenem-resistant B.
      thetaiotaomicron from a patient with postoperative intra-abdominal abscess and
      empyema. Whole-genome sequencing demonstrated the presence of nimD with at least
      a portion of IS1169 upstream, a second putative nim gene, two beta-lactamase
      genes (one of which has not been previously reported), two tetX genes, tetQ,
      ermF, two cat genes, and a number of efflux pumps. This report highlights
      emerging antimicrobial resistance in B. thetaiotaomicron and the importance of
      identification and antimicrobial susceptibility testing of selected anaerobic
      bacteria.

PMID- 25941221
TI  - Structure-activity relationship study of novel peptoids that mimic the structure
      of antimicrobial peptides.
AB  - The constant emergence of new bacterial strains that resist the effectiveness of
      marketed antimicrobials has led to an urgent demand for and intensive research on
      new classes of compounds to combat bacterial infections. Antimicrobial peptoids
      comprise one group of potential candidates for antimicrobial drug development.
      The present study highlights a library of 22 cationic amphipathic peptoids
      designed to target bacteria. All the peptoids share an overall net charge of +4
      and are 8 to 9 residues long; however, the hydrophobicity and charge distribution
      along the abiotic backbone varied, thus allowing an examination of the structure
      activity relationship within the library. In addition, the toxicity profiles of
      all peptoids were assessed in human red blood cells (hRBCs) and HeLa cells,
      revealing the low toxicity exerted by the majority of the peptoids. The
      structural optimization also identified two peptoid candidates, 3 and 4, with
      high selectivity ratios of 4 to 32 and 8 to 64, respectively, and a concentration
      dependent bactericidal mode of action against Gram-negative Escherichia coli.

PMID- 25941220
TI  - Determination of appropriate weight-based cutoffs for empiric cefazolin dosing
      using data from a phase 1 pharmacokinetics and safety study of cefazolin
      administered for surgical prophylaxis in pediatric patients aged 10 to 12 years.
AB  - Despite over 40 years of worldwide usage, relatively few data have been published
      on the pharmacokinetics of cefazolin in pediatric surgical patients. The primary
      objectives of this study were to examine the pharmacokinetics and safety of
      cefazolin in children 10 to 12 years of age (inclusive) receiving 1 or 2 g of
      cefazolin, based on body weight. This multiple-center, open-label study enrolled
      pediatric patients electively scheduled for surgical procedures who required
      cefazolin as part of their routine clinical management. Patients weighing >=25 to
      <50 kg received a 1-g dose, and patients weighing >=50 to <=85 kg received a 2-g
      dose. Postdose pharmacokinetic and safety assessments were conducted following
      drug administration. Cefazolin concentration-time data were analyzed by using
      both noncompartmental and population pharmacokinetics methods. Monte Carlo
      simulations were performed to identify appropriate weight-based cutoffs for the
      dosing of children aged 10 to 17 years of age. Twelve patients were enrolled in
      this study and provided the requisite pharmacokinetic data. In general, cefazolin
      was well tolerated. The mean cefazolin terminal elimination half-life, clearance,
      and area under the concentration-time curve from time zero to infinity in this
      population were 1.95 h, 0.804 ml/min/kg, and 607 mg . h/liter, respectively.
      Patients weighing 50 to 60 kg exhibited elevated cefazolin exposures. Observed
      pharmacokinetic parameters and simulation results indicated that a weight-based
      cutoff of 60 kg is predicted to provide cefazolin exposure consistent with that
      observed in normal, healthy adults at recommended doses for surgical prophylaxis.
      (This study has been registered at ClinicalTrials.gov under registration no.
      NCT01904357.).

PMID- 25941222
TI  - Oral administration of the nucleoside EFdA (4'-ethynyl-2-fluoro-2'
      deoxyadenosine) provides rapid suppression of HIV viremia in humanized mice and
      favorable pharmacokinetic properties in mice and the rhesus macaque.
AB  - Like normal cellular nucleosides, the nucleoside reverse transcriptase (RT)
      inhibitor (NRTI) 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) has a 3'-hydroxyl
      moiety, and yet EFdA is a highly potent inhibitor of human immunodeficiency virus
      (HIV) and simian immunodeficiency virus (SIV) replication with activity against a
      broad range of clinically important drug-resistant HIV isolates. We evaluated the
      anti-HIV activity of EFdA in primary human cells and in HIV-infected humanized
      mice. EFdA exhibited excellent potency against HIVJR-CSF in phytohemagglutinin
      stimulated peripheral blood mononuclear cells (PBMCs), with a 50% inhibitory
      concentration of 0.25 nM and a selectivity index of 184,000; similar antiviral
      potency was found against 12 different HIV clinical isolates from multiple clades
      (A, B, C, D, and CRF01_AE). EFdA was readily absorbed after oral dosing (5 mg/kg
      of body weight) in both mice and the rhesus macaque, with micromolar levels of
      the maximum concentration of drug in serum (Cmax) attained at 30 min and 90 min,
      respectively. Trough levels were at or above 90% inhibitory concentration (IC90)
      levels in the macaque at 24 h, suggesting once-daily dosing. EFdA showed
      reasonable penetration of the blood-brain barrier in the rhesus macaque, with
      cerebrospinal fluid levels at approximately 25% of plasma levels 8 h after single
      oral dosing. Rhesus PBMCs isolated 24 h following a single oral dose of 5 mg/kg
      EFdA were refractory to SIV infection due to sufficiently high intracellular EFdA
      triphosphate levels. The intracellular half-life of EFdA-triphosphate in PBMCs
      was determined to be >72 h following a single exposure to EFdA. Daily oral
      administration of EFdA at low dosage levels (1 to 10 mg/kg/day) was highly
      effective in protecting humanized mice from HIV infection, and 10 mg/kg/day oral
      EFdA completely suppressed HIV RNA to undetectable levels within 2 weeks of
      treatment.

PMID- 25941223
TI  - A sterilizing tuberculosis treatment regimen is associated with faster clearance
      of bacteria in cavitary lesions in marmosets.
AB  - Shortening the lengthy treatment duration for tuberculosis patients is a major
      goal of current drug development efforts. The common marmoset develops human-like
      disease pathology and offers an attractive model to better understand the basis
      for relapse and test regimens for effective shorter duration therapy. We treated
      Mycobacterium tuberculosis-infected marmosets with two drug regimens known to
      differ in their relapse rates in human clinical trials: the standard four-drug
      combination of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) that has
      very low relapse rates and the combination of isoniazid and streptomycin that is
      associated with higher relapse rates. As early as 2 weeks, the more sterilizing
      regimen significantly reduced the volume of lung disease by computed tomography
      (P = 0.035) and also significantly reduced uptake of [(18)F]-2-fluoro-2
      deoxyglucose by positron emission tomography (P = 0.049). After 6 weeks of
      therapy, both treatments caused similar reductions in granuloma bacterial load,
      but the more sterilizing, four-drug regimen caused greater reduction in bacterial
      load in cavitary lesions (P = 0.009). These findings, combined with the
      association in humans between cavitary disease and relapse, suggest that the
      basis for improved sterilizing activity of the four-drug combination is both its
      faster disease volume resolution and its stronger sterilizing effect on cavitary
      lesions. Definitive data from relapse experiments are needed to support this
      observation.

PMID- 25941224
TI  - Outbreak of NDM-1-producing Klebsiella pneumoniae causing neonatal infection in a
      teaching hospital in mainland China.
AB  - The emergence and spread of bacteria carrying the bla(NDM-1) gene has become a
      worldwide concern. Here, we report eight cases of Klebsiella pneumoniae with
      bla(NDM-1) in the neonatal ward of a teaching hospital in mainland China.
      Multilocus sequence typing showed that seven isolates were clonally related and
      confirmed them as sequence type 17 (ST17). One isolate belonged to ST433. These
      findings suggest continuous spread of bla(NDM-1) in mainland China and emphasize
      the need for intensive surveillance and precautions.

PMID- 25941225
TI  - A mutation of RNA polymerase beta' subunit (RpoC) converts heterogeneously
      vancomycin-intermediate Staphylococcus aureus (hVISA) into "slow VISA".
AB  - Various mutations in the rpoB gene, which encodes the RNA polymerase beta
      subunit, are associated with increased vancomycin (VAN) resistance in vancomycin
      intermediate Staphylococcus aureus (VISA) and heterogeneously VISA (hVISA)
      strains. We reported that rpoB mutations are also linked to the expression of the
      recently found "slow VISA" (sVISA) phenotype (M. Saito, Y. Katayama, T.
      Hishinuma, A. Iwamoto, Y. Aiba, K Kuwahara-Arai, L. Cui, M. Matsuo, N. Aritaka,
      and K. Hiramatsu, Antimicrob Agents Chemother 58:5024-5035, 2014,
      http://dx.doi.org/10.1128/AAC.02470-13). Because RpoC and RpoB are components of
      RNA polymerase, we examined the effect of the rpoC(P440L) mutation on the
      expression of the sVISA phenotype in the Mu3fdh2*V6-5 strain (V6-5), which was
      derived from a previously reported hVISA strain with the VISA phenotype. V6-5 had
      an extremely prolonged doubling time (DT) (72 min) and high vancomycin MIC (16
      mg/liter). However, the phenotype of V6-5 was unstable, and the strain frequently
      reverted to hVISA with concomitant loss of low growth rate, cell wall thickness,
      and reduced autolysis. Whole-genome sequencing of phenotypic revertant strain V6
      5-L1 and comparison with V6-5 revealed a second mutation, F562L, in rpoC.
      Introduction of the wild-type (WT) rpoC gene using a multicopy plasmid resolved
      the sVISA phenotype of V6-5, indicating that the rpoC(P440L) mutant expressed the
      sVISA phenotype in hVISA. To investigate the mechanisms of resistance in the
      sVISA strain, we independently isolated an additional 10 revertants to hVISA and
      VISA. In subsequent whole-genome analysis, we identified compensatory mutations
      in the genes of three distinct functional categories: the rpoC gene itself as
      regulatory mutations, peptidoglycan biosynthesis genes, and relQ, which is
      involved in the stringent response. It appears that the rpoC(P440L) mutation
      causes the sVISA phenotype by augmenting cell wall peptidoglycan synthesis and
      through the control of the stringent response.

PMID- 25941226
TI  - Determination of MIC distribution and epidemiological cutoff values for
      bedaquiline and delamanid in Mycobacterium tuberculosis using the MGIT 960 system
      equipped with TB eXiST.
AB  - Bedaquiline (Sirturo) and delamanid (Deltyba) have recently been approved by the
      regulatory authorities for treatment of multidrug-resistant tuberculosis (MDR
      TB). Antimicrobial susceptibility testing is not established for either
      substance. On the basis of the use of the MGIT 960 system equipped with
      EpiCenter/TB eXiST, we determined a mean bedaquiline MIC for wild-type strains of
      0.65 mg/liter (median, 0.4 mg/liter) and an epidemiological cutoff (ECOFF) of 1.6
      mg/liter; for delamanid, a mean wild-type drug MIC of 0.013 mg/liter (median,
      0.01 mg/liter) and an ECOFF of 0.04 mg/liter were determined.

PMID- 25941227
TI  - Development of Gendine-Coated Cannula for Continuous Subcutaneous Insulin
      Infusion for Extended Use.
AB  - Continuous subcutaneous insulin infusion (CSII) using pumps is a widely used
      method for insulin therapy in patients with diabetes mellitus. Among the major
      factors that usually lead to the discontinuation of CSII are CSII set-related
      issues, including infection at the infusion site. The American Diabetic
      Association currently recommends rotating sites every 2 to 3 days. This
      recommendation adds cost and creates inconvenience. Therefore, in order to
      prevent infections and extend the duration between insertion site changes, we
      developed a Teflon cannula coated with a combination of gentian violet and
      chlorhexidine (gendine) and tested its antimicrobial efficacy against different
      pathogens. The cannulas were coated with gendine on the exterior surface and
      dried. The efficacy and durability of gendine-coated cannulas were determined
      against methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis,
      methicillin-susceptible S. aureus, Streptococcus pyogenes, vancomycin-resistant
      enterococci, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, and
      Candida glabrata using a biofilm colonization method. The cytotoxicity of gendine
      was assessed against mouse fibroblast cell lines. The gendine-coated cannulas
      showed complete prevention of biofilm colonization of all organisms tested for up
      to 2 weeks (P < 0.0001) compared to that with the uncoated control. A gendine
      coated catheter against mouse fibroblast cells was shown to be noncytotoxic. Our
      in vitro results show that a novel gendine cannula is highly effective in
      completely inhibiting the biofilm of multidrug-resistant pathogens for up to 2
      weeks and may have potential clinical applications, such as prolonged use, cost
      reduction, and lower infection rate. 

PMID- 25941228
TI  - Splenic retention of Plasmodium falciparum gametocytes to block the transmission
      of malaria.
AB  - Plasmodium falciparum is transmitted from humans to Anopheles mosquito vectors
      via the sexual erythrocytic forms termed gametocytes. Erythrocyte filtration
      through microsphere layers (microsphiltration) had shown that circulating
      gametocytes are deformable. Compounds reducing gametocyte deformability would
      induce their splenic clearance, thus removing them from the blood circulation and
      blocking malaria transmission. The hand-made, single-sample prototype for
      microsphiltration was miniaturized to a 96-well microtiter plate format, and
      gametocyte retention in the microsphere filters was quantified by high-content
      imaging. The stiffening activity of 40 pharmacological compounds was assessed in
      microtiter plates, using a small molecule (calyculin) as a positive control. The
      stiffening activity of calyculin was assessed in spleen-mimetic microfluidic
      chips and in macrophage-depleted mice. Marked mechanical retention (80% to 90%)
      of mature gametocytes was obtained in microplates following exposure to calyculin
      at concentrations with no effect on parasite viability. Of the 40 compounds
      tested, including 20 antimalarials, only 5 endoperoxides significantly increased
      gametocyte retention (1.5- to 2.5-fold; 24 h of exposure at 1 MUM). Mature
      gametocytes exposed to calyculin accumulated in microfluidic chips and were
      cleared from the circulation of macrophage-depleted mice as rapidly as heat
      stiffened erythrocytes, thus confirming results obtained using the
      microsphiltration assay. An automated miniaturized approach to select compounds
      for their gametocyte-stiffening effect has been established. Stiffening induces
      gametocyte clearance both in vitro and in vivo. Based on physiologically
      validated tools, this screening cascade can identify novel compounds and uncover
      new targets to block malaria transmission. Innovative applications in hematology
      are also envisioned.

PMID- 25941229
TI  - Environmental isolates of azole-resistant Aspergillus fumigatus in Germany.
AB  - Azole antifungal drug resistance in Aspergillus fumigatus is an emerging problem
      in several parts of the world. Here we investigated the distribution of such
      strains in soils from Germany. At a general positivity rate of 12%, most
      prevalently, we found strains with the TR34/L98H and TR46/Y121F/T289A alleles,
      dispersed along a corridor across northern Germany. Comparison of the
      distributions of resistance alleles and genotypes between environment and
      clinical samples suggests the presence of local clinical clusters.

PMID- 25941230
TI  - Effects of surotomycin on Clostridium difficile viability and toxin production in
      vitro.
AB  - The increasing incidence and severity of infection by Clostridium difficile have
      stimulated attempts to develop new antimicrobial therapies. We report here the
      relative abilities of two antibiotics (metronidazole and vancomycin) in current
      use for treating C. difficile infection and of a third antimicrobial,
      surotomycin, to kill C. difficile cells at various stages of development and to
      inhibit the production of the toxin proteins that are the major virulence
      factors. The results indicate that none of the drugs affects the viability of
      spores at 8* MIC or 80* MIC and that all of the drugs kill exponential-phase
      cells when provided at 8* MIC. In contrast, none of the drugs killed stationary
      phase cells or inhibited toxin production when provided at 8* MIC and neither
      vancomycin nor metronidazole killed stationary-phase cells when provided at 80*
      MIC. Surotomycin, on the other hand, did kill stationary-phase cells when
      provided at 80* MIC but did so without inducing lysis.

PMID- 25941231
TI  - Involvement of Ca2+ in Vacuole Degradation Caused by a Rapid Temperature Decrease
      in Saintpaulia Palisade Cells: A Case of Gene Expression Analysis in a
      Specialized Small Tissue.
AB  - Saintpaulia (African violet) leaves are known to be damaged by a rapid
      temperature decrease when cold water is applied to the leaf surface; the injury
      is ascribed to the chloroplast damage caused by the cytosolic pH decrease
      following the degradation of the vacuolar membrane in the palisade cells. In this
      report, we present evidence for the involvement of Ca(2+) in facilitating the
      collapse of the vacuolar membrane and in turn in the temperature sensitivity of
      Saintpaulia leaves. In the presence of a Ca(2+) chelator (EGTA) or certain Ca(2+)
      channel inhibitors (Gd(3+) or La(3+)) but not others (verapamil or nifedipine),
      the pH of the vacuole, monitored through BCECF (2',7'-bis(carboxyethyl)-4 or 5
      carboxyfluorescein) fluorescence, did not increase in response to a rapid
      temperature drop. These pharmacological observations are consistent with the
      involvement of mechanosensitive Ca(2+) channels in the collapse of the vacuolar
      membrane. The high level of expression of an MCA- (Arabidopsis mechanosensitive
      Ca(2+) channel) like gene, a likely candidate for a mechanosensitive Ca(2+)
      channel(s) in plant cells, was confirmed in the palisade tissue in Saintpaulia
      leaves by using a newly developed method of gene expression analysis for the
      specialized small tissues. 

PMID- 25941232
TI  - A Receptor-Like Kinase, Related to Cell Wall Sensor of Higher Plants, is Required
      for Sexual Reproduction in the Unicellular Charophycean Alga, Closterium
      peracerosum-strigosum-littorale Complex.
AB  - Here, we cloned the CpRLK1 gene, which encodes a receptor-like protein kinase
      expressed during sexual reproduction, from the heterothallic Closterium
      peracerosum-strigosum-littorale complex, one of the closest unicellular alga to
      land plants. Mating-type plus (mt(+)) cells with knockdown of CpRLK1 showed
      reduced competence for sexual reproduction and formed an abnormally enlarged
      conjugation papilla after pairing with mt(-) cells. The knockdown cells were
      unable to release a naked gamete, which is indispensable for zygote formation. We
      suggest that the CpRLK1 protein is an ancient cell wall sensor that now functions
      to regulate osmotic pressure in the cell to allow proper gamete release. 

PMID- 25941234
TI  - Regulation of the NADPH Oxidase RBOHD During Plant Immunity.
AB  - Pathogen recognition induces the production of reactive oxygen species (ROS) by
      NADPH oxidases in both plants and animals. ROS have direct antimicrobial
      properties, but also serve as signaling molecules to activate further immune
      outputs. However, ROS production has to be tightly controlled to avoid
      detrimental effects on host cells, but yet must be produced in the right amount,
      at the right place and at the right time upon pathogen perception. Plant NADPH
      oxidases belong to the respiratory burst oxidase homolog (RBOH) family, which
      contains 10 members in the model plant Arabidopsis thaliana. The perception of
      pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors
      (PRRs) leads to a rapid, specific and strong production of ROS, which is
      dependent on RBOHD. RBOHD is mainly controlled by Ca(2+) via direct binding to EF
      hand motifs and phosphorylation by Ca(2+)-dependent protein kinases. Recent
      studies have, however, revealed a critical role for a Ca(2+)-independent
      regulation of RBOHD. The plasma membrane-associated cytoplasmic kinase BIK1
      (BOTRYTIS-INDUCED KINASE1), which is a direct substrate of the PRR complex,
      directly interacts with and phosphorylates RBOHD upon PAMP perception. Impairment
      of these phosphorylation events completely abolishes the function of RBOHD in
      immunity. These results suggest that RBOHD activity is tightly controlled by
      multilayered regulations. In this review, we summarize recent advances in our
      understanding of the regulatory mechanisms controlling RBOHD activation. 

PMID- 25941233
TI  - ABA Affects Brassinosteroid-Induced Antioxidant Defense via ZmMAP65-1a in Maize
      Plants.
AB  - Brassinosteroids (BRs) and ABA co-ordinately regulate water deficit tolerance in
      maize leaves. ZmMAP65-1a, a maize microtubule-associated protein (MAP) which
      plays an essential role in BR-induced antioxidant defense, has been characterized
      previously. However, the interactions among BR, ABA and ZmMAP65-1a in water
      deficit tolerance remain unexplored. In this study, we demonstrated that ABA was
      required for BR-induced antioxidant defense via ZmMAP65-1a by using biochemical
      blocking and ABA biosynthetic mutants. The expression of ZmMAP65-1a in maize
      leaves and mesophyll protoplasts could be increased under polyethylene glycol-
      (PEG) stimulated water deficit and ABA treatments. Furthermore, the importance of
      ABA in the early pathway of BR-induced water deficit tolerance was demonstrated
      by limiting ABA availability. Blocking ABA biosynthesis biochemically or by a
      null mutation inhibited the downstream gene expression of ZmMAP65-1a and the
      activity of ZmMAPK5 in the pathway. It also affected the activities of BR-induced
      antioxidant defense-related enzymes, namely ascorbate peroxidase (APX), catalase
      (CAT), glutathione reductase (GR), superoxide dismutase (SOD) and NADPH oxidase.
      In addition, combining results from transiently overexpressed or silenced ZmMAP65
      1a in mesophyll protoplasts, we discovered that ZmMAP65-1a mediated the ABA
      induced gene expression and activities of APX and SOD. Surprisingly, silencing of
      ZmMAP65-1a in mesophyll protoplasts did not alter the gene expression of ZmCCaMK
      and vice versa in response to ABA. Taken together, our data indicate that water
      deficit-induced ABA is a key mediator in BR-induced antioxidant defense via
      ZmMAP65-1a in maize. 

PMID- 25941235
TI  - Attaining and sustaining leadership for U.S. women in dentistry.

PMID- 25941236
TI  - Alternative careers for women in dentistry: impact, innovation, and industry.

PMID- 25941237
TI  - Harmonizing professional, personal, and social responsibilities: Indian women
      dentists' perspectives.
AB  - Women in Indian culture have a paradoxical status: on the one hand, goddesses are
      worshipped for power and prosperity; on the other hand, working women face
      challenges due to age-old beliefs and sociocultural norms. With 60% of the
      students enrolled in undergraduate dental education currently being women, there
      is a need to study the challenges these women are facing and how they tackle
      them. The aim of this survey study was to assess the barriers women dentists face
      in career advancement and how successfully they balance the personal,
      professional, and social aspects of their lives. Questionnaires, consisting of
      four qualitative and 24 quantitative items, were distributed to 500 women
      dentists: postgraduate residents and faculty members in dental colleges of Mumbai
      and Navi Mumbai, as well as private dental practitioners. Of the 500 women, 210
      returned the survey, for an overall response rate of 42%. The results showed that
      95% of the respondents believed they successfully balance the various spheres of
      their lives, but the most common challenges they faced continued to be
      traditional gender bias, dual professional and home responsibilities, and
      preconceived ideas about women. 

PMID- 25941238
TI  - Leveraging strengths to reach your goals: a skills-building workshop for women in
      dentistry and other professions.
AB  - This skills-building workshop at the 5(th) American Dental Education Association
      (ADEA) International Women's Leadership Conference engaged participants in a
      series of structured experiences designed to support learning about personal
      leadership strengths and areas for development, as well as setting and attaining
      leadership goals. The session was introduced with a brief reflective exercise
      focused on developing statements of personal goals for professional growth. An
      Appreciative Inquiry process then was used to explore participants' areas of
      strength, examining both self-perceptions and the perceptions of others who
      listened to their descriptions of "peak experiences" in work settings. The next
      part of the program utilized a Johari Window exercise to clarify the extent to
      which participants' self-perceived strengths and others' perceptions were shared,
      making those strengths visible to the world at large or hidden from the general
      view of others. This exercise allowed further exploration of individual
      competencies and characteristics and provided an opportunity for participants to
      visualize the potential for development in new areas. Finally, two very different
      peer coaching strategies were employed to expand on participants' learning. The
      experience proved to be a lively, socially engaging, and personally meaningful
      one for participants, whatever the stage of their careers or their country of
      origin. 

PMID- 25941239
TI  - Integrating Oral Health with Non-Communicable Diseases as an Essential Component
      of General Health: WHO's Strategic Orientation for the African Region.
AB  - In the context of the emerging recognition of non-communicable diseases (NCDs),
      it has never been more timely to explore the World Health Organization (WHO)
      strategic orientations on oral health in the WHO African region and to raise
      awareness of a turning point in the search for better oral health for everyone.
      The global initiative against NCDs provides a unique opportunity for the oral
      health community to develop innovative policies for better recognition of oral
      health, as well as to directly contribute to the fight against NCDs and their
      risk factors. The WHO African region has led the way in developing the first
      regional oral health strategy for the prevention and control of oral diseases
      integrated with NCDs. The support of the international oral health community in
      this endeavor is urgently needed for making a success story of this initiative of
      integrating oral health into NCDs. 

PMID- 25941240
TI  - Ethical considerations in community oral health.
AB  - As the public's oral health care needs increase in complexity, there is renewed
      attention to the ethical dimensions of community oral health decision making and
      the development of public health ethics in teaching and research in dentistry.
      Despite their reduction globally, oral diseases persist with a particular
      distribution pattern that is a reflection of the increasingly widespread
      inequality in access to community oral health preventive and dental care. This is
      due to differences in the appropriateness, availability, accessibility, and
      acceptability of oral health education and the care provided. This article
      provides an overview of community oral health from an ethical perspective,
      including the importance of equity, human rights, and social justice in providing
      oral health care to the underserved. The need for a paradigm shift from highly
      technical and individualistic dental training curricula is discussed, together
      with the need to instill a holistic approach to ethical and social responsibility
      in new dental graduates. It concludes with some possible strategies, using the
      overarching principles of ethics and bioethics that are applicable to practice
      among vulnerable populations. 

PMID- 25941241
TI  - Ethical oral health care and infection control.

PMID- 25941242
TI  - Interprofessional education and practice.

PMID- 25941245
TI  - The landscape for women leaders in dental education, research, and practice.
AB  - Following early limitations on women becoming educated in and practicing
      dentistry, the proportion of women enrolled in dental schools around the world
      has increased dramatically over the past decades. Dental schools have undergone a
      transformation from male dominance to almost equal numbers in the United States
      and female predominance in other countries including the United Kingdom. However,
      this change in student gender distribution has not been matched among academic
      leaders. Data from across the globe indicate a clear disproportion in favor of
      males in leadership positions in dentistry-and the more senior the position, the
      greater the imbalance. This article reviews the evolving changes in gender
      distribution across the landscape of dental education, research, and practice and
      some initiatives to address the gender imbalance in leadership. Such initiatives
      can help to ensure that, in the future, the profession benefits from the spectrum
      of influences brought to bear by the leadership of both women and men. 

PMID- 25941246
TI  - Study links dabigatran adherence to pharmacists' activities.

PMID- 25941247
TI  - Pharmacists say safety huddles aid problem solving.

PMID- 25941249
TI  - Studies underlying pharmacogenomics-based safety labeling can have inconsistent
      results.

PMID- 25941251
TI  - Micromanagement: When to avoid it and how to use it effectively.

PMID- 25941252
TI  - Development of an "infusion pump safety score".

PMID- 25941253
TI  - Assessing pharmacologic and nonpharmacologic risks in candidates for kidney
      transplantation.
AB  - PURPOSE: Pharmacotherapy concerns and other factors with a bearing on patient
      selection for kidney transplantation are discussed. SUMMARY: The process of
      selecting appropriate candidates for kidney transplantation involves
      multidisciplinary assessment to evaluate a patient's mental, social, physical,
      financial, and medical readiness for successful surgery and good
      posttransplantation outcomes. Transplantation pharmacists can play important
      roles in the recognition and stratification of pharmacologic and nonpharmacologic
      risks in prospective kidney transplant recipients and the identification of
      issues that require a mitigation strategy. Key pharmacotherapy-related issues and
      considerations during the risk assessment process include (1) anticoagulation
      concerns, (2) cytochrome P-450 isoenzyme-mediated drug interactions, (3) mental
      health-related medication use, (4) chronic pain-related medication use, (5)
      medication allergies, (6) use of hormonal contraception and replacement therapy,
      (7) prior or current use of immunosuppressants, (8) issues with drug absorption,
      (9) alcohol use, (10) tobacco use, (11) active use of illicit substances, and
      (12) use of herbal supplements. Important areas of nonpharmacologic risk include
      vaccine delivery, infection prophylaxis and treatment, and socially related
      factors such as nonadherent behavior, communication barriers, and financial,
      insurance, or transportation challenges that can compromise posttransplantation
      outcomes. CONCLUSION: Consensus opinions of practitioners in transplantation
      pharmacy regarding the pharmacologic and nonpharmacologic factors that should be
      considered in assessing candidates for kidney transplantation are presented.

PMID- 25941254
TI  - Replication of Plasmodium in reticulocytes can occur without hemozoin formation,
      resulting in chloroquine resistance.
AB  - Most studies on malaria-parasite digestion of hemoglobin (Hb) have been performed
      using P. falciparum maintained in mature erythrocytes, in vitro. In this study,
      we examine Plasmodium Hb degradation in vivo in mice, using the parasite P.
      berghei, and show that it is possible to create mutant parasites lacking enzymes
      involved in the initial steps of Hb proteolysis. These mutants only complete
      development in reticulocytes and mature into both schizonts and gametocytes. Hb
      degradation is severely impaired and large amounts of undigested Hb remains in
      the reticulocyte cytoplasm and in vesicles in the parasite. The mutants produce
      little or no hemozoin (Hz), the detoxification by-product of Hb degradation.
      Further, they are resistant to chloroquine, an antimalarial drug that interferes
      with Hz formation, but their sensitivity to artesunate, also thought to be
      dependent on Hb degradation, is retained. Survival in reticulocytes with reduced
      or absent Hb digestion may imply a novel mechanism of drug resistance. These
      findings have implications for drug development against human-malaria parasites,
      such as P. vivax and P. ovale, which develop inside reticulocytes. 

PMID- 25941255
TI  - IFN-lambda resolves inflammation via suppression of neutrophil infiltration and
      IL-1beta production.
AB  - The most studied biological role of type III interferons (IFNs) has so far been
      their antiviral activity, but their role in autoimmune and inflammatory diseases
      remains largely unexplored. Here, we show that treatment with IFN-lambda2/IL-28A
      completely halts and reverses the development of collagen-induced arthritis (CIA)
      and discover cellular and molecular mechanisms of IL-28A antiinflammatory
      function. We demonstrate that treatment with IL-28A dramatically reduces numbers
      of proinflammatory IL-17-producing Th17 and gammadelta T cells in the joints and
      inguinal lymph nodes, without affecting T cell proliferative responses or levels
      of anticollagen antibodies. IL-28A exerts its antiinflammatory effect by
      restricting recruitment of IL-1b-expressing neutrophils, which are important for
      amplification of inflammation. We identify neutrophils as cells expressing high
      levels of IFN-lambda receptor 1 (IFNLR1)-IL-28 receptor alpha (IL28RA) and
      targeted by IL-28A. Our data highlight neutrophils as contributors to the
      pathogenesis of autoimmune arthritis and present IFN-lambdas or agonists of
      IFNLR1-IL28RA as putative new therapeutics for neutrophil-driven inflammation. 

PMID- 25941257
TI  - RHEX, a novel regulator of human erythroid progenitor cell expansion and
      erythroblast development.

PMID- 25941258
TI  - Ebola crisis revealed "major fault lines".

PMID- 25941256
TI  - STAT3 is a critical cell-intrinsic regulator of human unconventional T cell
      numbers and function.
AB  - Unconventional T cells such as gammadelta T cells, natural killer T cells (NKT
      cells) and mucosal-associated invariant T cells (MAIT cells) are a major
      component of the immune system; however, the cytokine signaling pathways that
      control their development and function in humans are unknown. Primary
      immunodeficiencies caused by single gene mutations provide a unique opportunity
      to investigate the role of specific molecules in regulating human lymphocyte
      development and function. We found that individuals with loss-of-function
      mutations in STAT3 had reduced numbers of peripheral blood MAIT and NKT but not
      gammadelta T cells. Analysis of STAT3 mosaic individuals revealed that this
      effect was cell intrinsic. Surprisingly, the residual STAT3-deficient MAIT cells
      expressed normal levels of the transcription factor RORgammat. Despite this, they
      displayed a deficiency in secretion of IL-17A and IL-17F, but were able to
      secrete normal levels of cytokines such as IFNgamma and TNF. The deficiency in
      MAIT and NKT cells in STAT3-deficient patients was mirrored by loss-of-function
      mutations in IL12RB1 and IL21R, respectively. Thus, these results reveal for the
      first time the essential role of STAT3 signaling downstream of IL-23R and IL-21R
      in controlling human MAIT and NKT cell numbers.

PMID- 25941259
TI  - Vaccine needed for Aboriginal children.

PMID- 25941261
TI  - Can reporting of adverse drug reactions create safer systems while improving
      health data?

PMID- 25941262
TI  - More medical graduates than ever choosing family practice.

PMID- 25941263
TI  - Six new laureates in Canadian Medical Hall of Fame.

PMID- 25941264
TI  - Asbestos in Canada: time to change our legacy.

PMID- 25941265
TI  - PHAC chided for lack of antimicrobial resistance strategy.

PMID- 25941266
TI  - Olga ran.

PMID- 25941267
TI  - Cardiac testing in an asymptomatic 42-year-old man.

PMID- 25941268
TI  - Quantitative Rationalization of Gemfibrozil Drug Interactions: Consideration of
      Transporters-Enzyme Interplay and the Role of Circulating Metabolite Gemfibrozil
      1-O-beta-Glucuronide.
AB  - Gemfibrozil has been suggested as a sensitive cytochrome P450 2C8 (CYP2C8)
      inhibitor for clinical investigation by the U.S. Food and Drug Administration and
      the European Medicines Agency. However, gemfibrozil drug-drug interactions (DDIs)
      are complex; its major circulating metabolite, gemfibrozil 1-O-beta-glucuronide
      (Gem-Glu), exhibits time-dependent inhibition of CYP2C8, and both parent and
      metabolite also behave as moderate inhibitors of organic anion transporting
      polypeptide 1B1 (OATP1B1) in vitro. Additionally, parent and metabolite also
      inhibit renal transport mediated by OAT3. Here, in vitro inhibition data for
      gemfibrozil and Gem-Glu were used to assess their impact on the pharmacokinetics
      of several victim drugs (including rosiglitazone, pioglitazone, cerivastatin, and
      repaglinide) by employing both static mechanistic and dynamic physiologically
      based pharmacokinetic (PBPK) models. Of the 48 cases evaluated using the static
      models, about 75% and 98% of the DDIs were predicted within 1.5- and 2-fold of
      the observed values, respectively, when incorporating the interaction potential
      of both gemfibrozil and its 1-O-beta-glucuronide. Moreover, the PBPK model was
      able to recover the plasma profiles of rosiglitazone, pioglitazone, cerivastatin,
      and repaglinide under control and gemfibrozil treatment conditions. Analyses
      suggest that Gem-Glu is the major contributor to the DDIs, and its exposure
      needed to bring about complete inactivation of CYP2C8 is only a fraction of that
      achieved in the clinic after a therapeutic gemfibrozil dose. Overall, the complex
      interactions of gemfibrozil can be quantitatively rationalized, and the learnings
      from this analysis can be applied in support of future predictions of gemfibrozil
      DDIs. 

PMID- 25941269
TI  - DTB Select: 5 | May 2015.
AB  - NICE guidance on medicines optimisation ? Hormone replacement therapy and CVD ?
      MHRA advice on tiotropium ? Paracetamol and adverse effects ? Updated guidance on
      depression in children and young people ? Impact of HPV vaccination programmes ?
      NICE lowers threshold for diagnosing gestational diabetes ? Online learning
      module on corticosteroid adverse effects ? New quality standards on psychosis and
      schizophrenia. 

PMID- 25941270
TI  - Understanding the course of cognitive deficits over the onset of psychosis.

PMID- 25941271
TI  - The many dimensions of the Affordable Care Act.

PMID- 25941272
TI  - Among the elderly, many mental illnesses go undiagnosed.
AB  - Few health care providers have the training to address depression, anxiety, and
      other conditions in their older patients. 

PMID- 25941273
TI  - An Early Look At SHOP Marketplaces: Low Premiums, Adequate Plan Choice In Many,
      But Not All, States.
AB  - The Affordable Care Act created the Small Business Health Options Program (SHOP)
      Marketplaces to help small businesses provide health insurance to their
      employees. To attract the participation of substantial numbers of small
      employers, SHOP Marketplaces must demonstrate value-added features unavailable in
      the traditional small-group market. Such features could include lower premiums
      than those for plans offered outside the Marketplace and more extensive choices
      of carriers and plans. More choices are necessary for SHOP Marketplaces to offer
      the "employee choice model," in which employees may choose from many carriers and
      plans. This study compared the numbers of carriers and plans and premium levels
      in 2014 for plans offered through SHOP Marketplaces with those of plans offered
      only outside of the Marketplaces. An average of 4.3 carriers participated in each
      state's Marketplace, offering a total of forty-seven plans. Premiums for plans
      offered through SHOP Marketplaces were, on average, 7 percent less than those in
      the same metal tier offered only outside of the Marketplaces. Lower premiums and
      the participation of multiple carriers in most states are a source of optimism
      for future enrollment growth in SHOP Marketplaces. Lack of broker buy-in in many
      states and burdensome enrollment processes are major impediments to success.

PMID- 25941274
TI  - California hospital networks are narrower in Marketplace than in commercial
      plans, but access and quality are similar.
AB  - Do insurance plans offered through the Marketplace implemented by the State of
      California under the Affordable Care Act restrict consumers' access to hospitals
      relative to plans offered on the commercial market? And are the hospitals
      included in Marketplace networks of lower quality compared to those included in
      the commercial plans? To answer these questions, we analyzed differences in
      hospital networks across similar plan types offered both in the Marketplace and
      commercially, by region and insurer. We found that the common belief that
      Marketplace plans have narrower networks than their commercial counterparts
      appears empirically valid. However, there does not appear to be a substantive
      difference in geographic access as measured by the percentage of people residing
      in at least one hospital market area. More surprisingly, depending on the measure
      of hospital quality employed, the Marketplace plans have networks with comparable
      or even higher average quality than the networks of their commercial
      counterparts. 

PMID- 25941275
TI  - Eliminating Medicaid adult dental coverage in California led to increased dental
      emergency visits and associated costs.
AB  - Dental coverage for adults is an elective benefit under Medicaid. As a result of
      budget constraints, California Medicaid eliminated its comprehensive adult dental
      coverage in July 2009. We examined the impact of this policy change on emergency
      department (ED) visits by Medicaid-enrolled adults for dental problems in the
      period 2006-11. We found that the policy change led to a significant and
      immediate increase in dental ED use, amounting to more than 1,800 additional
      dental ED visits per year. Young adults, members of racial/ethnic minority
      groups, and urban residents were disproportionately affected by the policy
      change. Average yearly costs associated with dental ED visits increased by 68
      percent. The California experience provides evidence that eliminating Medicaid
      adult dental benefits shifts dental care to costly EDs that do not provide
      definitive dental care. The population affected by the Medicaid adult dental
      coverage policy is increasing as many states expand their Medicaid programs under
      the ACA. Hence, such evidence is critical to inform decisions regarding adult
      dental coverage for existing Medicaid enrollees and expansion populations. 

PMID- 25941276
TI  - ACA Provisions Associated With Increase In Percentage Of Young Adult Women
      Initiating And Completing The HPV Vaccine.
AB  - Affordable Care Act provisions implemented in 2010 required insurance plans to
      offer dependent coverage to people ages 19-25 and to provide targeted preventive
      services with zero cost sharing. These provisions both increased the percentage
      of young adults with any source of health insurance coverage and improved the
      generosity of coverage. We examined how these provisions affected use of the
      human papillomavirus (HPV) vaccine, which is among the most expensive of
      recommended vaccines, among young adult women. Using 2008-12 data from the
      National Health Interview Survey, we estimated that the 2010 policy
      implementation increased the likelihood of HPV vaccine initiation and completion
      by 7.7 and 5.8 percentage points, respectively, for women ages 19-25 relative to
      a control group of women age 18 or 26. These estimates translate to approximately
      1.1 million young women initiating and 854,000 young women completing the vaccine
      series. 

PMID- 25941277
TI  - Hospital closures had no measurable impact on local hospitalization rates or
      mortality rates, 2003-11.
AB  - The Affordable Care Act (ACA) set in motion payment changes that could put
      pressure on hospital finances and lead some hospitals to close. Understanding the
      impact of closures on patient care and outcomes is critically important. We
      identified 195 hospital closures in the United States between 2003 and 2011. We
      found no significant difference between the change in annual mortality rates for
      patients living in hospital service areas (HSAs) that experienced one or more
      closures and the change in rates in matched HSAs without a closure (5.5 percent
      to 5.2 percent versus 5.4 percent to 5.4 percent, respectively). Nor was there a
      significant difference in the change in all-cause mortality rates following
      hospitalization (9.1 percent to 8.2 percent in HSAs with a closure versus 9.0
      percent to 8.4 percent in those without a closure). HSAs with a closure had a
      drop in readmission rates compared to controls (19.4 percent to 18.2 percent
      versus 18.8 percent to 18.3 percent). Overall, we found no evidence that hospital
      closures were associated with worse outcomes for patients living in those
      communities. These findings may offer reassurance to policy makers and clinical
      leaders concerned about the potential acceleration of hospital closures as a
      result of health care reform. 

PMID- 25941278
TI  - Most Uninsured Adults Could Schedule Primary Care Appointments Before The ACA,
      But Average Price Was $160.
AB  - Provisions of the Affordable Care Act (ACA) allow millions more Americans to
      obtain health insurance. However, a sizable number of people remain uninsured
      because they live in states that have not expanded Medicaid coverage or because
      they feel that Marketplace coverage is not affordable. Using data from a ten
      state telephone survey in which callers posed as patients, we examined prices for
      primary care visits offered by physician offices to new uninsured patients in
      2012-13, prior to ACA insurance expansions. Patients were quoted a mean price of
      $160. Significantly lower prices for the uninsured were offered by family
      practice offices compared to general internists, in offices participating in
      Medicaid managed care plans, and in federally qualified health centers. Prices
      were also lower for offices in ZIP codes with higher poverty rates. Only 18
      percent of uninsured callers were told that they could bring less than the full
      amount to the visit and arrange to pay the rest later. ACA insurance expansions
      could greatly decrease out-of-pocket spending for low-income adults seeking
      primary care. However, benefits of health reform are likely to be greater in
      states expanding Medicaid eligibility. 

PMID- 25941279
TI  - Illinois law opens door to kidney transplants for undocumented immigrants.

PMID- 25941280
TI  - Redesigned geriatric emergency care may have helped reduce admissions of older
      adults to intensive care units.
AB  - Charged with transforming geriatric emergency care by applying palliative care
      principles, a process improvement team at New York City's Mount Sinai Medical
      Center developed the GEDI WISE (Geriatric Emergency Department Innovations in
      Care through Workforce, Informatics, and Structural Enhancements) model. The
      model introduced workforce enhancements for emergency department (ED) and adjunct
      staff, including role redefinition, retraining, and education in palliative care
      principles. Existing ED triage nurses screened patients ages sixty-five and older
      to identify those at high risk of ED revisit and hospital readmission. Once fully
      trained, these nurses screened all but 6 percent of ED visitors meeting the
      screening criteria. Newly hired ED nurse practitioners identified high-risk
      patients suitable for and desiring palliative and hospice care, then expedited
      referrals. Between January 2011 and May 2013 the percentage of geriatric ED
      admissions to the intensive care unit fell significantly, from 2.3 percent to 0.9
      percent, generating an estimated savings of more than $3 million to Medicare. The
      decline in these admissions cannot be confidently attributed to the GEDI WISE
      program because other geriatric care innovations were implemented during the
      study period. GEDI WISE programs are now running at Mount Sinai and two partner
      sites, and their potential to affect the quality and value of geriatric emergency
      care continues to be examined. 

PMID- 25941281
TI  - Linking uninsured patients treated in the emergency department to primary care
      shows some promise in Maryland.
AB  - Use of the emergency department (ED) has increased significantly over the past
      twenty years, especially among people who lack access to regular care, such as
      from a primary care provider. Not only are many ED visits avoidable, but
      receiving care through the ED also may disrupt continuity of care and result in
      increased overall health care costs. This article analyzes one of the twenty-nine
      local projects funded by the Centers for Medicare and Medicaid Services: the
      Emergency Department-Primary Care Connect initiative of the Primary Care
      Coalition of Montgomery County, Maryland. The initiative linked low-income or
      uninsured patients with local safety-net primary care providers. In the period
      2009-11, five participating hospital EDs referred 10,761 low-income uninsured ED
      patients to four local primary care clinics. The intervention did not
      significantly reduce overall subsequent ED visits, but there was a significant
      reduction in subsequent ED visits among the subpopulation with chronic physical
      or behavioral conditions if they had more than two visits to the same primary
      care clinic. Our findings suggest that expansion of safety-net clinics, combined
      with strategies to link high-need patients in the ED with these primary care
      providers, can reduce subsequent ED use. 

PMID- 25941282
TI  - Comparative effectiveness and cost-effectiveness analyses frequently agree on
      value.
AB  - The Patient-Centered Outcomes Research Institute, known as PCORI, was established
      by Congress as part of the Affordable Care Act (ACA) to promote evidence-based
      treatment. Provisions of the ACA prohibit the use of a cost-effectiveness
      analysis threshold and quality-adjusted life-years (QALYs) in PCORI comparative
      effectiveness studies, which has been understood as a prohibition on support for
      PCORI's conducting conventional cost-effectiveness analyses. This constraint
      complicates evidence-based choices where incremental improvements in outcomes are
      achieved at increased costs of care. How frequently this limitation inhibits
      efficient cost containment, also a goal of the ACA, depends on how often more
      effective treatment is not cost-effective relative to less effective treatment.
      We examined the largest database of studies of comparisons of effectiveness and
      cost-effectiveness to see how often there is disagreement between the more
      effective treatment and the cost-effective treatment, for various thresholds that
      may define good value. We found that under the benchmark assumption, disagreement
      between the two types of analyses occurs in 19 percent of cases. Disagreement is
      more likely to occur if a treatment intervention is musculoskeletal and less
      likely to occur if it is surgical or involves secondary prevention, or if the
      study was funded by a pharmaceutical company. 

PMID- 25941283
TI  - Most routine laboratory testing of pediatric psychiatric patients in the
      emergency department is not medically necessary.
AB  - We examined the patient characteristics and hospital charges associated with
      routine medical clearance laboratory screening tests in 1,082 children younger
      than age eighteen who were brought to the emergency department (ED) for
      involuntary mental health holds--that is, each patient was brought to the ED to
      be evaluated for being a danger to him- or herself or to others, for being
      gravely disabled (unable to meet his or her basic needs due to a mental
      disorder), or both--from July 2009 to December 2010. Testing was performed on 871
      of the children; all patients also received a clinical examination. The median
      charge for blood and urine testing together was $1,235, and the most frequent
      ordering pattern was the full comprehensive panel of tests. Of the patients with
      a nonconcerning clinical examination, 94.3 percent also had clinically
      nonsignificant test results. When we extrapolated cost savings to the national
      level, omitting routine screening laboratory tests in the population of pediatric
      patients presenting to the ED on an involuntary psychiatric hold with
      nonconcerning clinical exams could represent up to $90 million in savings
      annually, without reducing the ability to screen for emergency medical
      conditions. Provider-initiated diagnostic testing instead of routine screening
      would lead to significantly lower charges to the ED and the patient.

PMID- 25941284
TI  - Nursing home 5-star rating system exacerbates disparities in quality, by payer
      source.
AB  - Market-based reforms in health care, such as public reporting of quality, may
      inadvertently exacerbate disparities. We examined how the Centers for Medicare
      and Medicare Services' five-star rating system for nursing homes has affected
      residents who are dually enrolled in Medicare and Medicaid ("dual eligibles"), a
      particularly vulnerable and disadvantaged population. Specifically, we assessed
      the extent to which dual eligibles and non-dual eligibles avoided the lowest
      rated nursing homes and chose the highest-rated homes once the five-star rating
      system began, in late 2008. We found that both populations resided in better
      quality homes over time but that by 2010 the increased likelihood of choosing the
      highest-rated homes was substantially smaller for dual eligibles than for non
      dual eligibles. Thus, the gap in quality, as measured by a nursing home's star
      rating, grew over time. Furthermore, we found that the benefit of the five-star
      system to dual eligibles was largely due to providers' improving their ratings,
      not to consumers' choosing different providers. We present evidence suggesting
      that supply constraints play a role in limiting dual eligibles' responses to
      quality ratings, since high-quality providers tend to be located close to
      relatively affluent areas. Increases in Medicaid payment rates for nursing home
      services may be the only long-term solution. 

PMID- 25941285
TI  - Despite Resources From The ACA, Most States Do Little To Help Addiction Treatment
      Programs Implement Health Care Reform.
AB  - The Affordable Care Act (ACA) dramatically expands health insurance for addiction
      treatment and provides unprecedented opportunities for service growth and
      delivery model reform. Yet most addiction treatment programs lack the staffing
      and technological capabilities to respond successfully to ACA-driven system
      change. In light of these challenges, we conducted a national survey to examine
      how Single State Agencies for addiction treatment--the state governmental
      organizations charged with overseeing addiction treatment programs--are helping
      programs respond to new requirements under the ACA. We found that most Single
      State Agencies provide little assistance to addiction treatment programs. Most
      agencies are helping programs develop collaborations with other health service
      programs. However, fewer than half reported providing help in modernizing systems
      to support insurance participation, and only one in three provided assistance
      with enrollment outreach. In the absence of technical assistance, it is unlikely
      that addiction treatment programs will fully realize the ACA's promise to improve
      access to and quality of addiction treatment.

PMID- 25941286
TI  - Geographic variation in potentially avoidable hospitalizations in France.
AB  - Potentially avoidable hospitalizations are studied as an indirect measure of
      access to primary care. Understanding the determinants of these hospitalizations
      can help improve the quality, efficiency, and equity of health care delivery. Few
      studies have tackled the issue of potentially avoidable hospitalizations in
      France, and none has done so at the national level. We assessed disparities in
      potentially avoidable hospitalizations in France in 2012 and analyzed their
      determinants. The standardized rate of potentially avoidable hospitalizations
      ranged from 0.1 to 44.4 cases per 1,000 inhabitants, at the ZIP code level.
      Increased potentially avoidable hospitalizations were associated with higher
      mortality, lower density of acute care beds and ambulatory care nurses, lower
      median income, and lower education levels. This study unveils considerable
      variation in the rate of potentially avoidable hospitalizations in spite of
      France's mandatory, publicly funded health insurance system. In addition to
      epidemiological and sociodemographic factors, this study suggests that primary
      care organization plays a role in geographic disparities in potentially avoidable
      hospitalizations that might be addressed by increasing the number of nurses and
      enhancing team work in primary care. Policy makers should consider measuring
      potentially avoidable hospitalizations in France as an indicator of primary care
      organization. 

PMID- 25941287
TI  - Risky Business: New York City's Experience With Fear-Based Public Health
      Campaigns.
AB  - Fear-based public health campaigns have been the subject of an intense moral and
      empirical debate. We examined how New York City, under Mayor Michael Bloomberg,
      used fear-based appeals to confront three challenges to public health: high rates
      of tobacco use, obesity, and HIV infection. New York City's use of this type of
      messaging may have set a precedent. Other state and local health departments will
      have to navigate how and whether to use fear in a context where it is possible to
      assert that it can serve the interests of public health. But this will not reduce
      the need to carefully balance efficacy, uncertainty, stigma, marginalization,
      emotional burdens, justice, community participation, and scientific credibility. 

PMID- 25941288
TI  - Where do physicians train? Investigating public and private institutional
      pipelines.
AB  - Where a physician is educated-in a public or a private institution-affects his or
      her practice choices, including the likelihood of choosing a career in primary
      care. It is important to monitor the educational pipeline for physicians to
      ensure that a robust cadre of professionals is entering the health care workforce
      from public-sector institutions to meet the growing demand for primary care
      providers. 

PMID- 25941289
TI  - The fall: aligning the best care with standards of care at the end of life.
AB  - When her mother is hurt, a health care executive finds that the standardized care
      she championed isn't always appropriate. 

PMID- 25941290
TI  - Foundations Aiming To Improve Children's Health.

PMID- 25941292
TI  - Robot-assisted partial nephrectomy.

PMID- 25941293
TI  - Radical versus partial nephrectomy.

PMID- 25941294
TI  - The use of robotics in nephrectomy.

PMID- 25941295
TI  - Robot-assisted surgery: the authors reply.

PMID- 25941296
TI  - Incentives for sustaining innovation.

PMID- 25941297
TI  - Pharmaceutical innovation: the authors reply.

PMID- 25941298
TI  - Measuring outcomes of hospital care.

PMID- 25941299
TI  - Population health for children with asthma: time to let some fresh air in.

PMID- 25941300
TI  - Higher cost, but poorer outcomes: the US health disadvantage and implications for
      pediatrics.

PMID- 25941302
TI  - First pertussis vaccine dose and prevention of infant mortality.
AB  - BACKGROUND: American infants are at highest risk of severe pertussis and death.
      We investigated the role of >=1 pertussis vaccinations in preventing pertussis
      related deaths and risk markers for death among infants aged <42 days. METHODS:
      We analyzed characteristics of fatal and nonfatal infant pertussis cases reported
      nationally during 1991-2008. Infants were categorized into 2 age groups on the
      basis of eligibility to receive a first pertussis vaccine dose at age 6 weeks;
      dose 1 was considered valid if given >=14 days before illness onset.
      Multivariable logistic regression was used to estimate the effect of >=1
      pertussis vaccine doses on outcome and risk markers. RESULTS: Pertussis-related
      deaths occurred among 258 of 45 404 cases. Fatal and nonfatal cases were
      confirmed by culture (54% vs 49%) and polymerase chain reaction (31% vs 27%). All
      deaths occurred before age 34 weeks at illness onset; 64% occurred before age 6
      weeks. Among infants aged >=42 days, receiving >=1 doses of vaccine protected
      against death (adjusted odds ratio [aOR]: 0.28; 95% confidence interval [CI]:
      0.11-0.74), hospitalization (aOR: 0.69; 95% CI: 0.63-0.77), and pneumonia (aOR:
      0.80; 95% CI: 0.68-0.95). Risk was elevated for Hispanic ethnicity (aOR: 2.28;
      95% CI: 1.36-3.83) and American Indian/Alaska Native race (aOR: 5.15; 95% CI:
      2.37-11.2) and lower for recommended antibiotic treatment (aOR: 0.28; 95% CI:
      0.16-0.47). Among infants aged <42 days, risk was elevated for Hispanic ethnicity
      and lower with recommended antibiotic use. CONCLUSIONS: The first pertussis
      vaccine dose and antibiotic treatment protect against death, hospitalization, and
      pneumonia.

PMID- 25941301
TI  - The pharmacy-level asthma medication ratio and population health.
AB  - BACKGROUND AND OBJECTIVES: Community pharmacies may be positioned for an
      increased role in population health. We sought to develop a population-level
      measure of asthma medication fills and assess its relationship to asthma-related
      utilization. METHODS: We conducted a retrospective, ecological study (2010-2012).
      Medication data from a chain of pharmacies (n = 27) within 1 county were used to
      calculate a Pharmacy-level Asthma Medication Ratio (Ph-AMR), defined as
      controller fills divided by controller plus rescue fills. Higher values are
      superior because they indicate more controller compared with rescue fills. The
      outcome was the asthma-related utilization rate among children in the same census
      tract as the pharmacy, calculated by dividing all emergency visits and
      hospitalizations by the number of children in that tract. Covariates, including
      ecological measures of poverty and access to care, were used in multivariable
      linear regression. RESULTS: Overall, 35 467 medications were filled. The median
      Ph-AMR was 0.53 (range 0.38-0.66). The median utilization rate across included
      census tracts was 22.4 visits per 1000 child-years (range 1.3-60.9). Tracts with
      Ph-AMR <0.5 had significantly higher utilization rates than those with Ph-AMR
      >=0.5 (26.1 vs 9.9; P = .001). For every 0.1 increase in Ph-AMR, utilization
      rates decreased by 9.5 (P = .03), after adjustment for underlying poverty and
      access. Seasonal variation in fills was evident, but pharmacies in high-utilizing
      tracts filled more rescue than controller medications at nearly every point
      during the study period. CONCLUSIONS: Ph-AMR was independently associated with
      ecological childhood asthma morbidity. Pharmacies may be a community-based
      leverage point for improving population-level asthma control through targeted
      interventions.

PMID- 25941303
TI  - Treatment of ankyloglossia and breastfeeding outcomes: a systematic review.
AB  - OBJECTIVE: Ankyloglossia is a congenital condition characterized by an abnormally
      short, thickened, or tight lingual frenulum that restricts tongue mobility. The
      objective of this study was to systematically review literature on surgical and
      nonsurgical treatments for infants with ankyloglossia. METHODS: Medline,
      PsycINFO, Cumulative Index of Nursing and Allied Health Literature, and Embase
      were searched up to August 2014. Two reviewers independently assessed studies
      against predetermined inclusion/exclusion criteria. Two reviewers independently
      extracted data regarding participant and intervention characteristics and
      outcomes and assigned quality and strength-of-evidence ratings. RESULTS: Twenty
      nine studies reported breastfeeding effectiveness outcomes (5 randomized
      controlled trials [RCTs], 1 retrospective cohort, and 23 case series). Four RCTs
      reported improvements in breastfeeding efficacy by using either maternally
      reported or observer ratings, whereas 2 RCTs found no improvement with observer
      ratings. Although mothers consistently reported improved effectiveness after
      frenotomy, outcome measures were heterogeneous and short-term. Based on current
      literature, the strength of the evidence (confidence in the estimate of effect)
      for this issue is low. We included comparative studies published in English. The
      evidence base is limited, consisting of small studies, short-term outcomes, and
      little information to characterize participants adequately. No studies addressed
      nonsurgical interventions, longer-term breastfeeding or growth outcomes, or
      surgical intervention compared with other approaches to improve breastfeeding,
      such as lactation consultation. CONCLUSIONS: A small body of evidence suggests
      that frenotomy may be associated with mother-reported improvements in
      breastfeeding, and potentially in nipple pain, but with small, short-term studies
      with inconsistent methodology, strength of the evidence is low to insufficient.

PMID- 25941304
TI  - Policy strategies to reduce youth recreational marijuana use.

PMID- 25941305
TI  - Safety incidents in the primary care office setting.
AB  - BACKGROUND: In the United Kingdom, 26% of child deaths have identifiable failures
      in care. Although children account for 40% of family physicians' workload, little
      is known about the safety of care in the community setting. Using data from a
      national patient safety incident reporting system, this study aimed to
      characterize the pediatric safety incidents occurring in family practice.
      METHODS: We undertook a retrospective, cross-sectional, mixed methods study of
      pediatric reports submitted to the UK National Reporting and Learning System from
      family practice. Analysis involved detailed data coding using multiaxial
      frameworks, descriptive statistical analysis, and thematic analysis of a special
      case sample of reports. Using frequency distributions and cross-tabulations, the
      relationships between incident types and contributory factors were explored.
      RESULTS: Of 1788 reports identified, 763 (42.7%) described harm to children.
      Three crosscutting priority areas were identified: medication management,
      assessment and referral, and treatment. The 4 incident types associated with the
      most harmful outcomes are errors associated with diagnosis and assessment,
      delivery of treatment and procedures, referrals, and medication provision. Poor
      referral and treatment decisions in severely unwell or vulnerable children, along
      with delayed diagnosis and insufficient assessment of such children, featured
      prominently in incidents resulting in severe harm or death. CONCLUSION: This is
      the first analysis of nationally collected, family practice-related pediatric
      safety incident reports. Recommendations to mitigate harm in these priority areas
      include mandatory pediatric training for all family physicians; use of electronic
      tools to support diagnosis, management, and referral decision-making; and use of
      technological adjuncts such as barcode scanning to reduce medication errors.

PMID- 25941306
TI  - Annual summary of vital statistics: 2012-2013.
AB  - The number of births in the United States declined by 1% between 2012 and 2013,
      to a total of 3 932 181. The general fertility rate also declined 1% to 62.5
      births per 1000 women, the lowest rate ever reported. The total fertility rate
      was down by 1% in 2013 (to 1857.5 births per 1000 women). The teenage birth rate
      fell to another historic low in 2013, 26.5 births per 1000 women. Birth rates
      also declined for women 20 to 29 years, but the rates rose for women 30 to 39 and
      were unchanged for women 40 to 44. The percentage of all births that were to
      unmarried women declined slightly to 40.6% in 2013, from 40.7% in 2012. In 2013,
      the cesarean delivery rate declined to 32.7% from 32.8% for 2012. The preterm
      birth rate declined for the seventh straight year in 2013 to 11.39%; the low
      birth weight (LBW) rate was essentially unchanged at 8.02%. The infant mortality
      rate was 5.96 infant deaths per 1000 live births in 2013, down 13% from 2005
      (6.86). The age-adjusted death rate for 2013 was 7.3 deaths per 1000 population,
      unchanged from 2012. Crude death rates for children aged 1 to 19 years declined
      to 24.0 per 100 000 population in 2013, from 24.8 in 2012. Unintentional injuries
      and suicide were, respectively, the first and second leading causes of death in
      this age group. These 2 causes of death jointly accounted for 45.7% of all deaths
      to children and adolescents in 2013.

PMID- 25941307
TI  - Case report: Benefits and challenges of long-term eculizumab in atypical
      hemolytic uremic syndrome.
AB  - Atypical hemolytic uremic syndrome (aHUS) is caused by dysregulation of the
      complement system, leading to complement overactivation. A humanized anti-C5
      monoclonal antibody, eculizumab, has been available for the treatment of aHUS
      since 2011. The long-term safety and efficacy of this novel drug in the pediatric
      population remain under review. We present a child with a hybrid CFH/CFHR3 gene
      who, having had multiple disease relapses despite optimal treatment with plasma
      exchange, commenced eculizumab therapy in August 2010. She remains relapse free
      in follow-up at 52 months, and treatment has been well tolerated. The risk of
      meningococcal disease during this treatment is recognized. Despite vaccination
      against meningococcal disease and appropriate antibiotic prophylaxis, our patient
      developed meningococcal bacteremia 30 months into treatment. She presented with
      nonspecific symptoms but recovered without sequelae with appropriate treatment.
      We recommend that children be vaccinated against invasive meningococcal infection
      before beginning eculizumab therapy and take appropriate antibiotic prophylaxis
      during treatment, and we suggest that vaccine responses should be checked and
      followed annually. Clinicians need to maintain a high index of suspicion for
      invasive meningococcal disease. Neither vaccination nor antibiotic prophylaxis
      provides complete protection in patients on eculizumab therapy. The appropriate
      dosage of eculizumab needed to achieve remission in aHUS in the pediatric
      population is unknown. Having achieved remission in our patient, we monitor
      eculizumab and CH50 levels to evaluate ongoing blockade of the terminal
      complement cascade. Such information may help guide dosing intervals in the
      future.

PMID- 25941308
TI  - A quality improvement project to reduce length of stay for neonatal abstinence
      syndrome.
AB  - BACKGROUND AND OBJECTIVE: Neonatal abstinence syndrome (NAS), a self-limiting
      condition, is associated with clinical symptoms that may require pharmacological
      intervention. Optimal treatment of NAS remains undetermined, but the hospital
      length of stay (LOS) for patients with NAS is partially dependent upon a standard
      treatment protocol used. Prolonged LOS for patients with NAS can lead to adverse
      patient harm, impaired maternal-infant attachment, and significant health care
      costs. Therefore, we conducted a quality improvement study to reduce the LOS for
      infants with NAS. METHODS: In 2009, a multidisciplinary NAS Taskforce was created
      to implement a standardized treatment protocol, discuss the strengths and
      weaknesses of the current medical and nursing management, and improve
      communication among staff. Infants with NAS that required pharmacological
      intervention were followed throughout their hospitalization. Readmission within
      30 days of hospital discharge was tracked as a balancing measure. RESULTS: Ninety
      two infants were eligible for the project including 23 infants from a baseline
      period (January 2007-August 2009). Reliable monitoring of symptoms and the
      administration of a standardized morphine protocol effectively reduced LOS from
      36 days to 18 days by June 2012. This improvement was sustained through December
      2012. No patients were readmitted for NAS treatment. CONCLUSIONS: The most
      effective interventions that impacted LOS for infants with NAS were the
      development of a staff NAS education program and the implementation of a standard
      treatment protocol. The formation of the NAS Taskforce was also essential because
      it facilitated communication and the dissemination of vital treatment information
      among all clinical staff.

PMID- 25941310
TI  - Epidemic pertussis and acellular pertussis vaccine failure in the 21st century.

PMID- 25941309
TI  - Tdap vaccine effectiveness in adolescents during the 2012 Washington State
      pertussis epidemic.
AB  - BACKGROUND: Acellular pertussis vaccines replaced whole-cell vaccines for the 5
      dose childhood vaccination series in 1997. A sixth dose of pertussis-containing
      vaccine, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis,
      adsorbed (Tdap), was recommended in 2005 for adolescents and adults. Studies
      examining Tdap vaccine effectiveness (VE) among adolescents who have received all
      acellular vaccines are limited. METHODS: To assess Tdap VE and duration of
      protection, we conducted a matched case-control study during the 2012 pertussis
      epidemic in Washington among adolescents born during 1993-2000. All pertussis
      cases reported from January 1 through June 30, 2012, in 7 counties were included;
      3 controls were matched by primary provider clinic and birth year to each case.
      Vaccination histories were obtained through medical records, the state
      immunization registry, and parent interviews. Participants were classified by
      type of pertussis vaccine received on the basis of birth year: a mix of whole
      cell and acellular vaccines (1993-1997) or all acellular vaccines (1998-2000). We
      used conditional logistic regression to calculate odds ratios comparing Tdap
      receipt between cases and controls. RESULTS: Among adolescents who received all
      acellular vaccines (450 cases, 1246 controls), overall Tdap VE was 63.9% (95%
      confidence interval [CI]: 50% to 74%). VE within 1 year of vaccination was 73%
      (95% CI: 60% to 82%). At 2 to 4 years postvaccination, VE declined to 34% (95%
      CI: -0.03% to 58%). CONCLUSIONS: Tdap protection wanes within 2 to 4 years. Lack
      of long-term protection after vaccination is likely contributing to increases in
      pertussis among adolescents.

PMID- 25941311
TI  - Early psychosocial exposures, hair cortisol levels, and disease risk.
AB  - BACKGROUND: Early psychosocial exposures are increasingly recognized as being
      crucial to health throughout life. A possible mechanism could be physiologic
      dysregulation due to stress. Cortisol in hair is a new biomarker assessing long
      term hypothalamic-pituitary-adrenal axis activity. The objective was to
      investigate whether early-life adverse psychosocial circumstances influence
      infant cortisol levels in hair and health outcomes in children prospectively
      until age 10. METHODS: A cohort study in the general community using a
      questionnaire covering 11 psychosocial items in the family during pregnancy and
      the cumulative incidence of diagnoses until age 10 years in 1876 children.
      Cortisol levels in hair were measured by using a radioimmunoassay in those with
      sufficient hair samples at age 1, yielding a subsample of n = 209. RESULTS:
      Children with added psychosocial exposures had higher infant cortisol levels in
      hair (B = 0.40, P < .0001, adjusted for gender and size for gestational age) in a
      cumulative manner and were significantly more often affected by 12 of the 14 most
      common childhood diseases, with a general pattern of increasing odds ratios.
      CONCLUSIONS: The findings support the model of physiologic dysregulation as a
      plausible mechanism by which the duration and number of early detrimental
      psychosocial exposures determine health outcomes. The model indicates that the
      multiplicity of adversities should be targeted in future interventions and could
      help to identify children who are at high risk of poor health. Furthermore, given
      the prolonged nature of exposure to a stressful social environment, the novel
      biomarker of cortisol in hair could be of major importance.

PMID- 25941312
TI  - Treatment of ankyloglossia for reasons other than breastfeeding: a systematic
      review.
AB  - BACKGROUND AND OBJECTIVE: Children with ankyloglossia, an abnormally short,
      thickened, or tight lingual frenulum, may have restricted tongue mobility and
      sequelae, such as speech and feeding difficulties and social concerns. We
      systematically reviewed literature on feeding, speech, and social outcomes of
      treatments for infants and children with ankyloglossia. METHODS: Medline,
      PsycINFO, Cumulative Index of Nursing and Allied Health Literature, and Embase
      were searched. Two reviewers independently assessed studies against predetermined
      inclusion/exclusion criteria. Two investigators independently extracted data on
      study populations, interventions, and outcomes and assessed study quality.
      RESULTS: Two randomized controlled trials, 2 cohort studies, and 11 case series
      assessed the effects of frenotomy on feeding, speech, and social outcomes. Bottle
      feeding and social concerns, such as ability to use the tongue to eat ice cream
      and clean the mouth, improved more in treatment groups in comparative studies.
      Supplementary bottle feedings decreased over time in case series. Two cohort
      studies reported improvement in articulation and intelligibility with treatment.
      Other benefits were unclear. One randomized controlled trial reported improved
      articulation after Z-frenuloplasty compared with horizontal-to-vertical
      frenuloplasty. Numerous noncomparative studies reported speech benefits
      posttreatment; however, studies primarily discussed modalities, with outcomes
      including safety or feasibility, rather than speech. We included English-language
      studies, and few studies addressed longer-term speech, social, or feeding
      outcomes; nonsurgical approaches, such as complementary and alternative medicine;
      and outcomes beyond infancy, when speech or social concerns may arise.
      CONCLUSIONS: Data are currently insufficient for assessing the effects of
      frenotomy on nonbreastfeeding outcomes that may be associated with ankyloglossia.

PMID- 25941313
TI  - A Single Nucleotide Deletion in Gibberellin20-oxidase1 Causes Alpine Dwarfism in
      Arabidopsis.
AB  - Alpine dwarfism is widely observed in alpine plant populations and often
      considered a high-altitude adaptation, yet its molecular basis and ecological
      relevance remain unclear. In this study, we used map-based cloning and field
      transplant experiments to investigate dwarfism in natural Arabidopsis
      (Arabidopsis thaliana) accessions collected from the Swiss Alps. A loss-of
      function mutation due to a single nucleotide deletion in gibberellin20-oxidase1
      (GA5) was identified as the cause of dwarfism in an alpine accession. The mutated
      allele, ga5-184, was found in two natural Arabidopsis populations collected from
      one geographic region at high altitude, but was different from all other reported
      ga5 null alleles, suggesting that this allele has evolved locally. In field
      transplant experiments, the dwarf accession with ga5-184 exhibited a fitness
      pattern consistent with adaptation to high altitude. Across a wider array of
      accessions from the Swiss Alps, plant height decreased with altitude of origin,
      but fitness patterns in the transplant experiments were variable and general
      altitudinal adaptation was not evident. In general, our study provides new
      insights into molecular basis and possible ecological roles of alpine dwarfism,
      and demonstrates the importance of the GA-signaling pathway for the generation of
      ecologically relevant variation in higher plants. 

PMID- 25941314
TI  - MicroRNA167-Directed Regulation of the Auxin Response Factors GmARF8a and GmARF8b
      Is Required for Soybean Nodulation and Lateral Root Development.
AB  - Legume root nodules convert atmospheric nitrogen gas into ammonium through
      symbiosis with a prokaryotic microsymbiont broadly called rhizobia. Auxin
      signaling is required for determinant nodule development; however, the molecular
      mechanism of auxin-mediated nodule formation remains largely unknown. Here, we
      show in soybean (Glycine max) that the microRNA miR167 acts as a positive
      regulator of lateral root organs, namely nodules and lateral roots. miR167c
      expression was up-regulated in the vasculature, pericycle, and cortex of soybean
      roots following inoculation with Bradyrhizobium japonicum strain USDA110 (the
      microsymbiont). It was found to positively regulate nodule numbers directly by
      repressing the target genes GmARF8a and GmARF8b (homologous genes of Arabidopsis
      [Arabidopsis thaliana] AtARF8 that encode auxin response factors). Moreover, the
      expression of miR167 and its targets was up- and down-regulated by auxin,
      respectively. The miR167-GmARF8 module also positively regulated nodulation
      efficiency under low microsymbiont density, a condition often associated with
      environmental stress. The regulatory role of miR167 on nodule initiation was
      dependent on the Nod factor receptor GmNFR1alpha, and it acts upstream of the
      nodulation-associated genes nodule inception, nodulation signaling pathway1,
      early nodulin40-1, NF-YA1 (previously known as HAEM activator protein2-1), and NF
      YA2. miR167 also promoted lateral root numbers. Collectively, our findings
      establish a key role for the miR167-GmARF8 module in auxin-mediated nodule and
      lateral root formation in soybean.

PMID- 25941315
TI  - Tobacco Translationally Controlled Tumor Protein Interacts with Ethylene Receptor
      Tobacco Histidine Kinase1 and Enhances Plant Growth through Promotion of Cell
      Proliferation.
AB  - Ethylene is an important phytohormone in the regulation of plant growth,
      development, and stress response throughout the lifecycle. Previously, we
      discovered that a subfamily II ethylene receptor tobacco (Nicotiana tabacum)
      Histidine Kinase1 (NTHK1) promotes seedling growth. Here, we identified an NTHK1
      interacting protein translationally controlled tumor protein (NtTCTP) by the
      yeast (Saccharomyces cerevisiae) two-hybrid assay and further characterized its
      roles in plant growth. The interaction was further confirmed by in vitro
      glutathione S-transferase pull down and in vivo coimmunoprecipitation and
      bimolecular fluorescence complementation assays, and the kinase domain of NTHK1
      mediates the interaction with NtTCTP. The NtTCTP protein is induced by ethylene
      treatment and colocalizes with NTHK1 at the endoplasmic reticulum. Overexpression
      of NtTCTP or NTHK1 reduces plant response to ethylene and promotes seedling
      growth, mainly through acceleration of cell proliferation. Genetic analysis
      suggests that NtTCTP is required for the function of NTHK1. Furthermore,
      association of NtTCTP prevents NTHK1 from proteasome-mediated protein
      degradation. Our data suggest that plant growth inhibition triggered by ethylene
      is regulated by a unique feedback mechanism, in which ethylene-induced NtTCTP
      associates with and stabilizes ethylene receptor NTHK1 to reduce plant response
      to ethylene and promote plant growth through acceleration of cell proliferation. 

PMID- 25941317
TI  - Special delivery: how macrophages get the message across.

PMID- 25941316
TI  - Network Analyses Reveal Shifts in Transcript Profiles and Metabolites That
      Accompany the Expression of SUN and an Elongated Tomato Fruit.
AB  - SUN controls elongated tomato (Solanum lycopersicum) shape early in fruit
      development through changes in cell number along the different axes of growth.
      The gene encodes a member of the IQ domain family characterized by a calmodulin
      binding motif. To gain insights into the role of SUN in regulating organ shape,
      we characterized genome-wide transcriptional changes and metabolite and hormone
      accumulation after pollination and fertilization in wild-type and SUN fruit
      tissues. Pericarp, seed/placenta, and columella tissues were collected at 4, 7,
      and 10 d post anthesis. Pairwise comparisons between SUN and the wild type
      identified 3,154 significant differentially expressed genes that cluster in
      distinct gene regulatory networks. Gene regulatory networks that were enriched
      for cell division, calcium/transport, lipid/hormone, cell wall, secondary
      metabolism, and patterning processes contributed to profound shifts in gene
      expression in the different fruit tissues as a consequence of high expression of
      SUN. Promoter motif searches identified putative cis-elements recognized by known
      transcription factors and motifs related to mitotic-specific activator sequences.
      Hormone levels did not change dramatically, but some metabolite levels were
      significantly altered, namely participants in glycolysis and the tricarboxylic
      acid cycle. Also, hormone and primary metabolite networks shifted in SUN compared
      with wild-type fruit. Our findings imply that SUN indirectly leads to changes in
      gene expression, most strongly those involved in cell division, cell wall, and
      patterning-related processes. When evaluating global coregulation in SUN fruit,
      the main node represented genes involved in calcium-regulated processes,
      suggesting that SUN and its calmodulin binding domain impact fruit shape through
      calcium signaling. 

PMID- 25941318
TI  - DUSP4 phosphatase puts the brakes on DLBCL.

PMID- 25941319
TI  - T cell development runs marrow deep.

PMID- 25941320
TI  - Going with the flow: how shear stress signals the emergence of adult
      hematopoiesis.

PMID- 25941322
TI  - A critical role for the host mediator macrophage migration inhibitory factor in
      the pathogenesis of malarial anemia.

PMID- 25941321
TI  - Precision medicine: Clarity for the clinical and biological complexity of
      Alzheimer's and Parkinson's diseases.
AB  - The goal of precision medicine is to deliver optimally targeted and timed
      interventions tailored to an individual's molecular drivers of disease. This
      concept has wide currency in cancer care and in some diseases caused by
      monogenetic mutations, such as cystic fibrosis, and recently has been endorsed by
      the White House Office of Science and Technology for more widespread application
      in medicine. Here we describe our vision of how precision medicine can bring
      greater clarity to the clinical and biological complexity of the two most common
      neurodegenerative diseases, Alzheimer's disease and Parkinson's disease.

PMID- 25941323
TI  - Identifying the biological pathways underlying human focal epilepsy: from
      complexity to coherence to centrality.
AB  - Numerous diverse biological pathways are dysregulated in the epileptic focus.
      Which of these pathways are most critical in producing the biological
      abnormalities that lead to epilepsy? Answering this question is key to
      identifying the primary causes of epilepsy and for discovering new therapeutic
      strategies with greater efficacy than currently available antiepileptics (AEDs).
      We have performed the largest genome-wide transcriptomic analysis to date
      comparing epileptic with normal human hippocampi. We have identified 118
      differentially expressed and, for the first time, differentially connected
      pathways in the epileptic focus. Using network mapping techniques, we have shown
      that these dysregulated pathways, though seemingly disparate, form a coherent
      interconnected central network. Using closeness centrality analysis, we have
      identified that the most influential hub pathways in this network are signalling
      through G protein-coupled receptors, in particular opioid receptors, and their
      downstream effectors PKA/CREB and DAG/IP3. Next, we have objectively demonstrated
      that genetic association of gene sets in independent genome-wide association
      studies (GWASs) can be used to identify causally relevant gene sets: we show that
      proven causal epilepsy genes, which cause familial Mendelian epilepsy syndromes,
      are associated in published sporadic epilepsy GWAS results. Using the same
      technique, we have shown that central pathways identified (opioid receptor and
      PKA/CREB and DAG/IP3 signalling pathways) are genetically associated with focal
      epilepsy and, hence, likely causal. Published functional studies in animal models
      provide evidence of a role for these pathways in epilepsy. Our work shows that
      these pathways play a central role in human focal epilepsy and that they are
      important currently unexploited antiepileptic drug targets. 

PMID- 25941326
TI  - Accumulation of long-lived mRNAs associated with germination in embryos during
      seed development of rice.
AB  - Mature dry seeds contain translatable mRNAs called long-lived mRNAs. Early
      studies have shown that protein synthesis during the initial phase of seed
      germination occurs from long-lived mRNAs, without de novo transcription. However,
      the gene expression systems that generate long-lived mRNAs in seeds are not well
      understood. To examine the accumulation of long-lived mRNAs in developing rice
      embryos, germination tests using the transcriptional inhibitor actinomycin D (Act
      D) were performed with the Japonica rice cultivar Nipponbare. Although over 70%
      of embryos at 10 days after flowering (DAF) germinated in the absence of the
      inhibitor, germination was remarkably impaired in embryos treated with Act D. In
      contrast, more than 70% of embryos at 20, 25, 30 and 40 DAF germinated in the
      presence of Act D. The same results were obtained when another cultivar,
      Koshihikari, was used, indicating that the long-lived mRNAs required for
      germination predominantly accumulate in embryos between 10 and 20 DAF during seed
      development. RNA-Seq identified 529 long-lived mRNA candidates, encoding proteins
      such as ABA, calcium ion and phospholipid signalling-related proteins, and HSP
      DNA J, increased from 10 to 20 DAF and were highly abundant in 40 DAF embryos of
      Nipponbare and Koshihikari. We also revealed that these long-lived mRNA
      candidates are clearly up-regulated in 10 DAF germinating embryos after
      imbibition, suggesting that the accumulation of these mRNAs in embryos is
      indispensable for the induction of germination. The findings presented here may
      facilitate in overcoming irregular seed germination or producing more vigorous
      seedlings. 

PMID- 25941325
TI  - Genetic variants in adult bone mineral density and fracture risk genes are
      associated with the rate of bone mineral density acquisition in adolescence.
AB  - Previous studies have identified 63 single-nucleotide polymorphisms (SNPs)
      associated with bone mineral density (BMD) in adults. These SNPs are thought to
      reflect variants that influence bone maintenance and/or loss in adults. It is
      unclear whether they affect the rate of bone acquisition during adolescence. Bone
      measurements and genetic data were available on 6397 individuals from the Avon
      Longitudinal Study of Parents and Children at up to five follow-up clinics.
      Linear mixed effects models with smoothing splines were used for longitudinal
      modelling of BMD and its components bone mineral content (BMC) and bone area
      (BA), from 9 to 17 years. Genotype data from the 63 adult BMD associated SNPs
      were investigated individually and as a genetic risk score in the longitudinal
      model. Each additional BMD lowering allele of the genetic risk score was
      associated with lower BMD at age 13 [per allele effect size, 0.002 g/cm(2) (SE =
      0.0001, P = 1.24 * 10(-38))] and decreased BMD acquisition from 9 to 17 years (P
      = 9.17 * 10(-7)). This association was driven by changes in BMC rather than BA.
      The genetic risk score explained ~2% of the variation in BMD at 9 and 17 years, a
      third of that explained in adults (6%). Genetic variants that putatively affect
      bone maintenance and/or loss in adults appear to have a small influence on the
      rate of bone acquisition through adolescence. 

PMID- 25941324
TI  - Identification of a novel FGFRL1 MicroRNA target site polymorphism for bone
      mineral density in meta-analyses of genome-wide association studies.
AB  - MicroRNAs (miRNAs) are critical post-transcriptional regulators. Based on a
      previous genome-wide association (GWA) scan, we conducted a polymorphism in
      microRNA target sites (poly-miRTS)-centric multistage meta-analysis for lumbar
      spine (LS)-, total hip (HIP)- and femoral neck (FN)-bone mineral density (BMD).
      In stage I, 41 102 poly-miRTSs were meta-analyzed in seven cohorts with a genome
      wide significance (GWS) alpha = 0.05/41 102 = 1.22 * 10(-6). By applying alpha =
      5 * 10(-5) (suggestive significance), 11 poly-miRTSs were selected, with FGFRL1
      rs4647940 and PRR5 rs3213550 as top signals for FN-BMD (P = 7.67 * 10(-6) and
      1.58 * 10(-5)) in gender-combined sample. In stage II in silico replication (two
      cohorts), FGFRL1 rs4647940 was the only signal marginally replicated for FN-BMD
      (P = 5.08 * 10(-3)) at alpha = 0.10/11 = 9.09 * 10(-3). PRR5 rs3213550 was also
      selected based on biological significance. In stage III de novo genotyping
      replication (two cohorts), FGFRL1 rs4647940 was the only signal significantly
      replicated for FN-BMD (P = 7.55 * 10(-6)) at alpha = 0.05/2 = 0.025 in gender
      combined sample. Aggregating three stages, FGFRL1 rs4647940 was the single stage
      I-discovered and stages II- and III-replicated signal attaining GWS for FN-BMD (P
      = 8.87 * 10(-12)). Dual-luciferase reporter assays demonstrated that FGFRL1 3'
      untranslated region harboring rs4647940 appears to be hsa-miR-140-5p's target
      site. In a zebrafish microinjection experiment, dre-miR-140-5p is shown to exert
      a dramatic impact on craniofacial skeleton formation. Taken together, we provided
      functional evidence for a novel FGFRL1 poly-miRTS rs4647940 in a previously known
      4p16.3 locus, and experimental and clinical genetics studies have shown both
      FGFRL1 and hsa-miR-140-5p are important for bone formation. 

PMID- 25941327
TI  - Laser-assisted intradermal delivery of adjuvant-free vaccines targeting XCR1+
      dendritic cells induces potent antitumoral responses.
AB  - The development of vaccines inducing efficient CD8(+) T cell responses is the
      focus of intense research. Dendritic cells (DCs) expressing the XCR1 chemokine
      receptor, also known as CD103(+) or CD8alpha(+) DCs, excel in the presentation of
      extracellular Ags to CD8(+) T cells. Because of its high numbers of DCs,
      including XCR1(+) DCs, the skin dermis is an attractive site for vaccine
      administration. By creating laser-generated micropores through the epidermis, we
      targeted a model protein Ag fused to XCL1, the ligand of XCR1, to dermal XCR1(+)
      DCs and induced Ag-specific CD8(+) and CD4(+) T cell responses. Efficient
      immunization required the emigration of XCR1(+) dermal DCs to draining lymph
      nodes and occurred irrespective of TLR signaling. Moreover, a single intradermal
      immunization protected mice against melanoma tumor growth in prophylactic and
      therapeutic settings, in the absence of exogenous adjuvant. The mild inflammatory
      milieu created in the dermis by skin laser microporation itself most likely
      favored the development of potent T cell responses in the absence of exogenous
      adjuvants. The existence of functionally equivalent XCR1(+) dermal DCs in humans
      should permit the translation of laser-assisted intradermal delivery of a tumor
      specific vaccine targeting XCR1(+) DCs to human cancer immunotherapy. Moreover,
      considering that the use of adjuvants in vaccines is often associated with safety
      issues, the possibility of inducing protective responses against melanoma tumor
      growth independently of the administration of exogenous adjuvants should
      facilitate the development of safer vaccines.

PMID- 25941328
TI  - De novo-developed antibodies to donor MHC antigens lead to dysregulation of
      microRNAs and induction of MHC class II.
AB  - Immune responses to HLA and development of anti-donor HLA (DSA) were shown to
      play a role in chronic rejection following transplantation. We hypothesized that
      Abs to MHC change microRNAs (miRNAs), leading to chronic lung allograft
      rejection. Microarray analysis was performed in a murine model of anti-MHC
      induced obliterative airway disease (OAD), a correlate of obliterative
      bronchiolitis. A unique profile of dysregulated miRNAs was detected in OAD mice
      on days 7 and 15 after Ab administration compared with control. Sixty-seven
      miRNAs were increased and 42 miRNAs were decreased in OAD mice on day 7. In
      addition, 15 miRNAs were overexpressed and 16 miRNAs were underexpressed in OAD
      mice on day 15. The expression of miR-16 and miR-195 was significantly decreased
      in lungs of OAD mice, as assessed by quantitative RT-PCR and in situ
      hybridization, with increases in H-2 Aa and H-2 Dma mRNA levels. Significant
      reductions in miR-16 and miR-195 levels were also noted in lung transplant (LTx)
      patients with DSA compared with LTx patients without DSA. Bioinformatic
      TargetScan and reporter assays identified the binding of miR-16 and miR-195 to
      the 3'-untranslated region of regulatory factor X 5. Quantitative PCR and
      immunohistochemistry indicated posttranscriptional increases in regulatory factor
      X 5 mRNA and protein expression in OAD mice, as well as in LTx recipients with
      DSA, which was associated with increased expression of HLA-DPA1, HLA-DQA1, and
      HLA-DRA mRNA. Therefore, our results demonstrated that miRNAs induced by
      alloimmunity may play important roles in chronic rejection after LTx.

PMID- 25941329
TI  - Diverse inflammatory cytokines induce selectin ligand expression on murine CD4 T
      cells via p38alpha MAPK.
AB  - Selectins are glycan-binding adhesion molecules that mediate the initial steps of
      leukocyte recognition of endothelium. Cytokines control numerous aspects of CD4
      Th cell differentiation, but how cytokines control the induction of ligands for E
      and P-selectin on Th cell subsets remains poorly understood. Among 20 cytokines
      that affect Th cell differentiation, we identified six that induce expression of
      selectin ligands on murine CD4 T cells above the low levels associated with TCR
      engagement: IL-12, IL-18, IL-27, IL-9, IL-25, and TGF-beta1. Collectively, these
      six cytokines could potentially account for selectin ligand expression on all of
      the currently defined nonsessile Th cell lineages, including Th1, Th2, Th9, and
      Th17 cells, as well as regulatory T cells. Induction of selectin ligand
      expression by each of these six cytokines was almost completely inhibited by
      pharmacologic inhibition of p38 MAPK, but not other MAPKs, or by conditional
      genetic deletion of p38alpha MAPK. Analysis of the expression of key
      glycosyltransferase genes revealed that p38alpha signaling was selectively
      required for induction of Fut7 and Gcnt1 but not for the induction of St3gal4 or
      St3gal6. Constitutively active MKK6, an immediate upstream activator of p38 MAPK,
      induced selectin ligand expression equivalent to that of cytokines, and this
      induction was completely dependent on the expression of p38alpha. Our results
      identify the repertoire of cytokines responsible for selectin ligand induction on
      CD4 T cells and provide a mechanistic link between Th cell development and T cell
      migration.

PMID- 25941330
TI  - Predictors of Influenza Diagnosis Among Patients With Laboratory-Confirmed
      Influenza.
AB  - OBJECTIVE: This study was performed to determine predictors of clinical influenza
      diagnosis among patients with laboratory-confirmed influenza. METHODS:
      Prospective, laboratory-confirmed surveillance for influenza was conducted among
      patients of all ages who were hospitalized or presented to the emergency
      department with fever and respiratory symptoms during 2009-2013. We evaluated all
      enrolled persons who had influenza confirmed by viral culture and/or polymerase
      chain reaction and received any discharge diagnosis. The primary outcome,
      clinical influenza diagnosis, was defined as (1) a discharge diagnosis of
      influenza, (2) a prescription of neuraminidase inhibitor, or (3) a rapid test
      positive for influenza virus. Bivariate analyses and multiple logistic regression
      modeling were performed. RESULTS: Influenza was diagnosed for 29% of 504 enrolled
      patients with laboratory-confirmed influenza and for 56% of 236 patients with
      high-risk conditions. Overall, clinical influenza diagnosis was predicted by
      race/ethnicity, insurance status, year, being hospitalized, having high-risk
      conditions, and receiving no diagnosis of bacterial infection. Being diagnosed
      with a bacterial infection reduced the odds of receiving an influenza diagnosis
      by >3-fold for all patients and for patients with high-risk conditions.
      CONCLUSIONS: Many influenza virus-positive patients, including those with high
      risk conditions, do not receive a clinical diagnosis of influenza. The pattern of
      clinical diagnoses among influenza virus-positive patients suggests preferential
      consideration of bacterial diseases as a diagnosis.

PMID- 25941331
TI  - Frequent Asymptomatic Respiratory Syncytial Virus Infections During an Epidemic
      in a Rural Kenyan Household Cohort.
AB  - BACKGROUND: The characteristics, determinants, and potential contribution to
      transmission of asymptomatic cases of respiratory syncytial virus (RSV) infection
      have not been well described. METHODS: A cohort of 47 households (493
      individuals) in coastal Kenya was recruited and followed for a 26-week period
      spanning a complete RSV season. Nasopharyngeal swab specimens were requested
      weekly, during the first 4 weeks, and twice weekly thereafter from all household
      members, regardless of illness status. The samples were screened for a range of
      respiratory viruses by multiplex real-time polymerase chain reaction. RESULTS:
      Tests on 16,928 samples yielded 205 RSV infection episodes in 179 individuals
      (37.1%) from 40 different households. Eighty-six episodes (42.0%) were
      asymptomatic. Factors independently associated with an increased risk of
      asymptomatic RSV infection episodes were higher age, shorter duration of
      infection, bigger household size, lower peak viral load, absence of concurrent
      RSV infections within the household, infection by RSV group B, and no prior human
      rhinovirus infections. The propensity of RSV spread in households was dependent
      on symptom status and amount (duration and load) of virus shed. CONCLUSIONS:
      While asymptomatic RSV was less likely to spread, the high frequency of
      symptomless RSV infection episodes highlights a potentially important role of
      asymptomatic infections in the community transmission of RSV.

PMID- 25941332
TI  - Entry of Ebola Virus is an Asynchronous Process.
AB  - Ebola virus (EBOV) is responsible for a severe fever with a high mortality rate.
      The diverse nature of the attachment of the virus to the cell surface, the
      initial step of virus entry, raises questions concerning the kinetics of the
      virus internalization process. We investigated EBOV entry kinetics using the
      activity of a particular monoclonal antibody that neutralizes virus infectivity.
      We demonstrate that inoculation of cells with EBOV results in an asynchronous
      entry process, as revealed by the ability of the virus to remain in a cell-bound
      state for an extended period of time before it is internalized. 

PMID- 25941333
TI  - Relationship Between Ebola Virus Real-Time Quantitative Polymerase Chain Reaction
      Based Threshold Cycle Value and Virus Isolation From Human Plasma.
AB  - We performed a longitudinal analysis of plasma samples obtained from 4 patients
      with Ebola virus (EBOV) disease (EVD) to determine the relationship between the
      real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR)
      based threshold cycle (Ct) value and the presence of infectious EBOV. EBOV was
      not isolated from plasma samples with a Ct value of >35.5 or >12 days after onset
      of symptoms. EBOV was not isolated from plasma samples in which anti-EBOV
      nucleoprotein immunoglobulin G was detected. These data demonstrate the utility
      of interpreting qRT-PCR results in the context of the course of EBOV infection
      and associated serological responses for patient-management decisions. 

PMID- 25941336
TI  - RAI2: Linking Retinoic Acid Signaling with Metastasis Suppression.
AB  - Considerable evidence points to the importance of disseminated tumor cells, which
      are commonly detected in the bone marrow and display features of cellular
      plasticity, in predicting the clinical outcome of breast cancer. In this issue of
      Cancer Discovery, Werner and colleagues report on the discovery of retinoic acid
      induced 2 (RAI2) as a differentiation factor that suppresses early metastatic
      spread of estrogen receptor-positive breast cancer.

PMID- 25941337
TI  - Tumor twitter: cellular communication in the breast cancer stem cell niche.
AB  - Communication between the diverse assortment of cells that constitute the tumor
      microenvironment plays an important role in tumor development. Using a p53-null
      mouse model, Zhang and colleagues describe a novel feedback loop involving breast
      cancer stem cells and their progeny mediated by WNT2, CXCL12, and IL6.

PMID- 25941338
TI  - Understanding the MIG6-EGFR Signaling Axis in Lung Tumorigenesis.
AB  - With multiple clinical trials under way targeting mutant EGFR in patients with
      lung cancer, Maity and colleagues address important aspects of a MIG6-EGFR
      signaling axis using genetically engineered mouse models expressing mutated EGFRs
      on the MIG6-deficient background. This study extends our understanding of EGFR
      regulation by MIG6 and reveals that MIG6 antagonizes tumor formation in mutant
      EGFR-driven lung adenocarcinoma.

PMID- 25941339
TI  - An information theoretic method to identify combinations of genomic alterations
      that promote glioblastoma.
AB  - Tumors are the result of accumulated genomic alterations that cooperate
      synergistically to produce uncontrollable cell growth. Although identifying
      recurrent alterations among large collections of tumors provides a way to
      pinpoint genes that endow a selective advantage in oncogenesis and progression,
      it fails to address the genetic interactions behind this selection process. A non
      random pattern of co-mutated genes is evidence for selective forces acting on
      tumor cells that harbor combinations of these genetic alterations. Although
      existing methods have successfully identified mutually exclusive gene sets, no
      current method can systematically discover more general genetic relationships. We
      develop Genomic Alteration Modules using Total Correlation (GAMToC), an
      information theoretic framework that integrates copy number and mutation data to
      identify gene modules with any non-random pattern of joint alteration.
      Additionally, we present the Seed-GAMToC procedure, which uncovers the mutational
      context of any putative cancer gene. The software is publicly available. Applied
      to glioblastoma multiforme samples, GAMToC results show distinct subsets of co
      occurring mutations, suggesting distinct mutational routes to cancer and
      providing new insight into mutations associated with proneural, proneural/G-CIMP,
      and classical types of the disease. The results recapitulate known relationships
      such as mutual exclusive mutations, place these alterations in the context of
      other mutations, and find more complex relationships such as conditional mutual
      exclusivity. 

PMID- 25941340
TI  - Increased Epithelial Sodium Channel Activity Contributes to Hypertension Caused
      by Na+-HCO3- Cotransporter Electrogenic 2 Deficiency.
AB  - The gene SLC4A5 encodes the Na(+)-HCO3 (-) cotransporter electrogenic 2, which is
      located in the distal nephron. Genetically deleting Na(+)-HCO3 (-) cotransporter
      electrogenic 2 (knockout) causes Na(+)-retention and hypertension, a phenotype
      that is diminished with alkali loading. We performed experiments with acid-loaded
      mice and determined whether overactive epithelial Na(+) channels (ENaC) or the
      Na(+)-Cl(-) cotransporter causes the Na(+) retention and hypertension in
      knockout. In untreated mice, the mean arterial pressure was higher in knockout,
      compared with wild-type (WT); however, treatment with amiloride, a blocker of
      ENaC, abolished this difference. In contrast, hydrochlorothiazide, an inhibitor
      of Na(+)-Cl(-) cotransporter, decreased mean arterial pressure in WT, but not
      knockout. Western blots showed that quantity of plasmalemmal full-length ENaC
      alpha was significantly higher in knockout than in WT. Amiloride treatment caused
      a 2-fold greater increase in Na(+) excretion in knockout, compared with WT. In
      knockout, but not WT, amiloride treatment decreased plasma [Na(+)] and urinary
      K(+) excretion, but increased hematocrit and plasma [K(+)] significantly.
      Micropuncture with microelectrodes showed that the [K(+)] was significantly
      higher and the transepithelial potential (Vte) was significantly lower in the
      late distal tubule of the knockout compared with WT. The reduced Vte in knockout
      was amiloride sensitive and therefore revealed an upregulation of electrogenic
      ENaC-mediated Na(+) reabsorption in this segment. These results show that, in the
      absence of Na(+)-HCO3 (-) cotransporter electrogenic 2 in the late distal tubule,
      acid-loaded mice exhibit disinhibition of ENaC-mediated Na(+) reabsorption, which
      results in Na(+) retention, K(+) wasting, and hypertension. 

PMID- 25941341
TI  - Reexamining the Effect of Antihypertensive Medications on Falls in Old Age.
AB  - Conflicting data on the relationship between antihypertensive medications and
      falls in elderly people may lead to inappropriate undertreatment of hypertension
      in an effort to prevent falls. We aimed to clarify the relationships between the
      chronic use of different classes of antihypertensive medications and different
      types of falls, to determine the effect of medication dose, and to assess whether
      the risk of falls is associated with differences in cerebral blood flow. We
      assessed demographics, clinical characteristics, and chronic antihypertensive
      medication use in 598 community-dwelling people with hypertension, aged 70 to 97
      years, then followed them prospectively for self-reported falls using monthly
      calendar postcards and telephone interviews. Antihypertensive medication use was
      not associated with an increased risk of falls. Participants reporting use of
      angiotensin-converting enzyme inhibitors had a significantly decreased 1-year
      risk of injurious falls (odds ratio, 0.62; 95% confidence interval, 0.39-0.96),
      whereas those using calcium channel blockers had a decreased risk of all falls
      (odds ratio, 0.62; 95% confidence interval, 0.42-0.91) and indoor falls (odds
      ratio, 0.57; 95% confidence interval, 0.36-0.91), compared with participants not
      taking these drugs. Larger doses of these classes were associated with a lower
      fall risk. Participants taking calcium channel blockers had higher cerebral blood
      flow than those not taking these medications. In relatively healthy community
      dwelling elderly people, high doses of antihypertensive agents are not associated
      with an increased risk of falls. 

PMID- 25941342
TI  - Longitudinal Blood Pressure Control, Long-Term Mortality, and Predictive Utility
      of Serum Liver Enzymes and Bilirubin in Hypertensive Patients.
AB  - There is accruing evidence from general population studies that serum bilirubin
      and liver enzymes affect blood pressure (BP) and cardiovascular risk, but it is
      unclear whether these have an impact on hypertensive patients in terms of long
      term survival or BP control. We analyzed 12 000 treated hypertensive individuals
      attending a tertiary care clinic followed up for 35 years for association between
      baseline liver function tests and cause-specific mortality after adjustment for
      conventional cardiovascular covariates. Generalized estimating equations were
      used to study the association of liver tests and follow-up BP. The total time at
      risk was 173 806 person years with median survival 32.3 years. Follow-up systolic
      BP over 5 years changed by -0.4 (alanine transaminase and bilirubin),
      +2.1(alkaline phosphatase), +0.9(gamma-glutamyl transpeptidase) mm Hg for each
      standard deviation increase. Serum total bilirubin and alanine transaminase
      showed a significant negative association with all-cause and cardiovascular
      mortality, whereas alkaline phosphatase and gamma-glutamyl transpeptidase showed
      a positive association and aspartate transaminase showed a U-shapedassociation.
      Serum bilirubin showed an incremental improvement of continuous net
      reclassification improvement by 8% to 26% for 25 year and 35 year cardiovascular
      mortality, whereas all liver markers together improved continuous net
      reclassification improvement by 19% to 47% compared with reference model. In
      hypertensive patients, serum liver enzymes and bilirubin within 4 standard
      deviations of the mean show independent effects on mortality and BP control. Our
      findings would support further studies to elucidate the mechanisms by which liver
      enzymes and bilirubin may exert an effect on BP and cardiovascular risk, but
      there is little support for using them in risk stratification. 

PMID- 25941343
TI  - Classical Complement Pathway Activation in the Kidneys of Women With
      Preeclampsia.
AB  - A growing body of evidence suggests that complement dysregulation plays a role in
      the pathogenesis of preeclampsia. The kidney is one of the major organs affected
      in preeclampsia. Because the kidney is highly susceptible to complement
      activation, we hypothesized that preeclampsia is associated with renal complement
      activation. We performed a nationwide search for renal autopsy material in the
      Netherlands using a computerized database (PALGA). Renal tissue was obtained from
      11 women with preeclampsia, 25 pregnant controls, and 14 nonpregnant controls
      with hypertension. The samples were immunostained for C4d, C1q, mannose-binding
      lectin, properdin, C3d, C5b-9, IgA, IgG, and IgM. Preeclampsia was significantly
      associated with renal C4d-a stable marker of complement activation-and the
      classical pathway marker C1q. In addition, the prevalence of IgM was
      significantly higher in the kidneys of the preeclamptic women. No other
      complement markers studied differed between the groups. Our findings in human
      samples were validated using a soluble fms-like tyrosine kinase 1 mouse model of
      preeclampsia. The kidneys in the soluble fms-like tyrosine kinase 1-injected mice
      had significantly more C4 deposits than the control mice. The association between
      preeclampsia and renal C4d, C1q, and IgM levels suggests that the classical
      complement pathway is involved in the renal injury in preeclampsia. Moreover, our
      finding that soluble fms-like tyrosine kinase 1-injected mice develop excess C4
      deposits indicates that angiogenic dysregulation may play a role in complement
      activation within the kidney. We suggest that inhibiting complement activation
      may be beneficial for preventing the renal manifestations of preeclampsia. 

PMID- 25941344
TI  - Stages in Discovery: Angiotensin-Converting Enzyme Type 2 and Stroke.

PMID- 25941345
TI  - Chronic Hypertension Leads to Neurodegeneration in the TgSwDI Mouse Model of
      Alzheimer's Disease.
AB  - Numerous epidemiological studies link vascular disorders, such as hypertension,
      diabetes mellitus, and stroke, with Alzheimer's disease (AD). Hypertension,
      specifically, is an important modifiable risk factor for late-onset AD. To
      examine the link between midlife hypertension and the onset of AD later in life,
      we chemically induced chronic hypertension in the TgSwDI mouse model of AD in
      early adulthood. Hypertension accelerated cognitive deficits in the Barnes maze
      test (P<0.05 after 3 months of treatment; P<0.001 after 6 months), microvascular
      deposition of beta-amyloid (P<0.001 after 3 months of treatment; P<0.05 after 6
      months), vascular inflammation (P<0.05 in the dentate gyrus and P<0.001 in the
      dorsal subiculum after 6 months of treatment), blood-brain barrier leakage
      (P<0.05 after 3 and 6 months of treatment), and pericyte loss (P<0.05 in the
      dentate gyrus and P<0.01 in the dorsal subiculum after 6 months of treatment) in
      these mice. In addition, hypertension induced hippocampal neurodegeneration at an
      early age in this mouse line (43% reduction in the dorsal subiculum; P<0.05),
      establishing this as a useful research model of AD with mixed vascular and
      amyloid pathologies. 

PMID- 25941346
TI  - Activation of the Neuroprotective Angiotensin-Converting Enzyme 2 in Rat Ischemic
      Stroke.
AB  - The angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas axis represents a
      promising target for inducing stroke neuroprotection. Here, we explored stroke
      induced changes in expression and activity of endogenous angiotensin-converting
      enzyme 2 and other system components in Sprague-Dawley rats. To evaluate the
      clinical feasibility of treatments that target this axis and that may act in
      synergy with stroke-induced changes, we also tested the neuroprotective effects
      of diminazene aceturate, an angiotensin-converting enzyme 2 activator,
      administered systemically post stroke. Among rats that underwent experimental
      endothelin-1-induced ischemic stroke, angiotensin-converting enzyme 2 activity in
      the cerebral cortex and striatum increased in the 24 hours after stroke. Serum
      angiotensin-converting enzyme 2 activity was decreased within 4 hours post
      stroke, but rebounded to reach higher than baseline levels 3 days post stroke.
      Treatment after stroke with systemically applied diminazene resulted in decreased
      infarct volume and improved neurological function without apparent increases in
      cerebral blood flow. Central infusion of A-779, a Mas receptor antagonist,
      resulted in larger infarct volumes in diminazene-treated rats, and central
      infusion of the angiotensin-converting enzyme 2 inhibitor MLN-4760 alone worsened
      neurological function. The dynamic alterations of the protective angiotensin
      converting enzyme 2 pathway after stroke suggest that it may be a favorable
      therapeutic target. Indeed, significant neuroprotection resulted from poststroke
      angiotensin-converting enzyme 2 activation, likely via Mas signaling in a blood
      flow-independent manner. Our findings suggest that stroke therapeutics that
      target the angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas axis may
      interact cooperatively with endogenous stroke-induced changes, lending promise to
      their further study as neuroprotective agents. 

PMID- 25941347
TI  - Determinants of Aortic Root Dilatation and Reference Values Among Young Adults
      Over a 20-Year Period: Coronary Artery Risk Development in Young Adults Study.
AB  - Aortic size increases with age, but factors related to such dilatation in healthy
      young adult population have not been studied. We aim to evaluate changes in
      aortic dimensions and its principal correlates among young adults over a 20-year
      time period. Reference values for aortic dimensions in young adults by
      echocardiography are also provided. Healthy Coronary Artery Risk Development in
      Young Adults (CARDIA) study participants aged 23 to 35 years in 1990-1991
      (n=3051) were included after excluding 18 individuals with significant valvular
      dysfunction. Aortic root diameter (ARD) by M-mode echocardiography at year-5
      (43.7% men; age, 30.2 +/- 3.6 years) and year-25 CARDIA exams was obtained.
      Univariable and multivariable analyses were performed to assess associations of
      ARD with clinical data at years-5 and -25. ARD from year-5 was used to establish
      reference values of ARD in healthy young adults. ARD at year-25 was greater in
      men (33.3 +/- 3.7 versus 28.7 +/- 3.4 mm; P<0.001) and in whites (30.9 +/- 4.3
      versus 30.5 +/- 4.1 mm; P=0.006). On multivariable analysis, ARD at year-25 was
      positively correlated with male sex, white ethnicity, age, height, weight, 20
      year gain in weight, active smoking at baseline, and 20-year increase in
      diastolic, systolic, and mean arterial pressure. A figure showing the estimated
      95th percentile of ARD by age and body surface area stratified by race and sex is
      provided. This study demonstrates that smoking, blood pressure, and increase in
      body weight are the main modifiable correlates of aortic root dilation during
      young adulthood. Our study also provides reference values for ARD in young
      adults.

PMID- 25941348
TI  - Baroreflex activation therapy lowers arterial pressure without apparent
      stimulation of the carotid bodies.
AB  - Carotid baroreflex activation therapy produces a sustained fall in blood pressure
      in patients with resistant hypertension. Because the activation electrodes are
      implanted at the level of the carotid sinus, it is conceivable that the nearby
      located carotid body chemoreceptors are stimulated as well. Physiological
      stimulation of the carotid chemoreceptors not only stimulates respiration but
      also increases sympathetic activity, which may counteract the effects of
      baroreflex activation. The aim of this exploratory study is to investigate
      whether there is concomitant carotid chemoreflex activation during baroreflex
      activation therapy. Fifteen participants with the Rheos system were included in
      this single-center study. At arrival at the clinic, the device was switched off
      for 2 hours while patients were at rest. Subsequently, the device was switched on
      at 6 electric settings of high and low frequencies and amplitudes. Respiration
      and blood pressure measurements were performed during all device activation
      settings. Multilevel statistical models were adjusted for age, sex, body mass
      index, antihypertensive therapeutic index, sleep apnea, coronary artery disease,
      systolic blood pressure, and heart rate. There was no change in end-tidal carbon
      dioxide, partial pressure of carbon dioxide, breath duration, and breathing
      frequency during any of the electric settings with the device. Nevertheless, mean
      arterial pressure showed a highly significant decrease during electric activation
      (P<0.001). Carotid baroreflex activation therapy using the Rheos system did not
      stimulate respiration at several electric device activation energies, which
      suggests that there is no appreciable coactivation of carotid body chemoreceptors
      during device therapy.

PMID- 25941349
TI  - A mutation of MET, encoding hepatocyte growth factor receptor, is associated with
      human DFNB97 hearing loss.
AB  - BACKGROUND: Hearing loss is a heterogeneous neurosensory disorder. Mutations of
      56 genes are reported to cause recessively inherited non-syndromic deafness.
      OBJECTIVE: We sought to identify the genetic lesion causing hearing loss
      segregating in a large consanguineous Pakistani family. METHODS AND RESULTS:
      Mutations of GJB2 and all other genes reported to underlie recessive deafness
      were ruled out as the cause of the phenotype in the affected members of the
      participating family. Homozygosity mapping with a dense array of one million SNP
      markers allowed us to map the gene for recessively inherited severe hearing loss
      to chromosome 7q31.2, defining a new deafness locus designated DFNB97 (maximum
      logarithm of the odds score of 4.8). Whole-exome sequencing revealed a novel
      missense mutation c.2521T>G (p.F841V) in MET (mesenchymal epithelial transition
      factor), which encodes the receptor for hepatocyte growth factor. The mutation
      cosegregated with the hearing loss phenotype in the family and was absent from
      800 chromosomes of ethnically matched control individuals as well as from 136 602
      chromosomes in public databases of nucleotide variants. Analyses by multiple
      prediction programmes indicated that p.F841V likely damages MET function.
      CONCLUSIONS: We identified a missense mutation of MET, encoding the hepatocyte
      growth factor receptor, as a likely cause of hearing loss in humans.

PMID- 25941350
TI  - CARD9 Promotes Sex-Biased Colon Tumors in the APCmin Mouse Model.
AB  - Caspase recuitment domain-containing protein 9 (CARD9) functions in different
      inflammation pathways to elicit responses to microbial signals and is known to
      affect intestinal inflammation. Examining the APC(min) mouse model of intestinal
      tumorigenesis and using stringently controlled, sex- and age-matched pairs of
      CARD9-competent and CARD9-deficient mice, we have found that CARD9 has a
      restricted but strong effect on tumorigenesis in the large intestine. We have
      found that CARD9 reduces viability specifically in males and promotes
      tumorigenesis specifically in the large intestines of these male mice. To our
      knowledge, this is the first gene ablation in APC(min) mice that solely affects
      colon tumors in male subjects and, as such, may have significant clinical
      implications. Additional data suggest correlative disruption of plasma cytokine
      expression and immune infiltration of the tumors. We speculate that known sex
      specific differences in human colorectal cancer may involve inflammation,
      particularly CARD9-dependent inflammation.

PMID- 25941351
TI  - Generation of Potent T-cell Immunotherapy for Cancer Using DAP12-Based,
      Multichain, Chimeric Immunoreceptors.
AB  - Chimeric antigen receptors (CAR) bearing an antigen-binding domain linked in cis
      to the cytoplasmic domains of CD3zeta and costimulatory receptors have provided a
      potent method for engineering T-cell cytotoxicity toward B-cell leukemia and
      lymphoma. However, resistance to immunotherapy due to loss of T-cell effector
      function remains a significant barrier, especially in solid malignancies. We
      describe an alternative chimeric immunoreceptor design in which we have fused a
      single-chain variable fragment for antigen recognition to the transmembrane and
      cytoplasmic domains of KIR2DS2, a stimulatory killer immunoglobulin-like receptor
      (KIR). We show that this simple, KIR-based CAR (KIR-CAR) triggers robust antigen
      specific proliferation and effector function in vitro when introduced into human
      T cells with DAP12, an immunotyrosine-based activation motifs-containing adaptor.
      T cells modified to express a KIR-CAR and DAP12 exhibit superior antitumor
      activity compared with standard first- and second-generation CD3zeta-based CARs
      in a xenograft model of mesothelioma highly resistant to immunotherapy. The
      enhanced antitumor activity is associated with improved retention of chimeric
      immunoreceptor expression and improved effector function of isolated tumor
      infiltrating lymphocytes. These results support the exploration of KIR-CARs for
      adoptive T-cell immunotherapy, particularly in immunotherapy-resistant solid
      tumors.

PMID- 25941352
TI  - Tumoricidal Effects of Macrophage-Activating Immunotherapy in a Murine Model of
      Relapsed/Refractory Multiple Myeloma.
AB  - Myeloma remains a virtually incurable malignancy. The inevitable evolution of
      multidrug-resistant clones and widespread clonal heterogeneity limit the
      potential of traditional and novel therapies to eliminate minimal residual
      disease (MRD), a reliable harbinger of relapse. Here, we show potent anti-myeloma
      activity of macrophage-activating immunotherapy (alphaCD40+CpG) that resulted in
      prolongation of progression-free survival (PFS) and overall survival (OS) in an
      immunocompetent, preclinically validated, transplant-based model of multidrug
      resistant, relapsed/refractory myeloma (t-Vkappa*MYC). alphaCD40+CpG was
      effective in vivo in the absence of cytolytic natural killer, T, or B cells and
      resulted in expansion of M1-polarized (cytolytic/tumoricidal) macrophages in the
      bone marrow. Moreover, we show that concurrent loss/inhibition of Tpl2 kinase
      (Cot, Map3k8), a MAP3K that is recruited to activated CD40 complex and regulates
      macrophage activation/cytokine production, potentiated direct, ex vivo anti
      myeloma tumoricidal activity of alphaCD40+CpG-activated macrophages, promoted
      production of antitumor cytokine IL12 in vitro and in vivo, and synergized with
      alphaCD40+CpG to further prolong PFS and OS in vivo. Our results support the
      combination of alphaCD40-based macrophage activation and TPL2 inhibition for
      myeloma immunotherapy. We propose that alphaCD40-mediated activation of innate
      antitumor immunity may be a promising approach to control/eradicate MRD following
      cytoreduction with traditional or novel anti-myeloma therapies.

PMID- 25941353
TI  - Long-Term Lithium Use and Risk of Renal and Upper Urinary Tract Cancers.
AB  - Lithium induces proliferation in the epithelium of renal collecting ducts. A
      recent small-scale cohort study reported a strong association between use of
      lithium and increased risk of renal neoplasia. We therefore conducted a large
      scale pharmacoepidemiologic study of the association between long-term use of
      lithium and risk of upper urinary tract cancer, including renal cell cancer and
      cancers of the renal pelvis or ureter. We identified all histologically verified
      upper urinary tract cancer cases in Denmark between 2000 and 2012 from the Danish
      Cancer Registry. A total of 6477 cases were matched by age and sex to 259,080
      cancer-free controls. Data on lithium use from 1995 to 2012 were obtained from
      the Danish Prescription Registry. We estimated the association between long-term
      use of lithium (>=5 years) and risk of upper urinary tract cancer using
      conditional logistic regression with adjustment for potential confounders. Long
      term use of lithium was observed among 0.22% of cases and 0.17% of controls. This
      yielded an overall nonsignificant adjusted odds ratio (OR) of 1.3 (95% confidence
      interval [95% CI], 0.8-2.2) for upper urinary tract cancer associated with long
      term use of lithium. Analyses stratified by stage and subtype of upper urinary
      tract cancer revealed slight but nonsignificant increases in the ORs for
      localized disease (OR, 1.6; 95% CI, 0.8-3.0) and for renal pelvis/ureter cancers
      (OR, 1.7; 95% CI, 0.5-5.4). In conclusion, in our nationwide case-control study,
      use of lithium was not associated with an increased risk of upper urinary tract
      cancer. 

PMID- 25941356
TI  - Cancer immunotherapy out of the gate: the 22nd annual Cancer Research Institute
      International Immunotherapy Symposium.
AB  - The 22nd annual Cancer Research Institute (CRI) International Immunotherapy
      Symposium was held from October 5-8, 2014, in New York City. Titled "Cancer
      Immunotherapy: Out of the Gate," the symposium began with a Cancer Immunotherapy
      Consortium satellite meeting focused on issues in immunotherapy drug development,
      followed by five speaker sessions and a poster session devoted to basic and
      clinical cancer immunology research. The second annual William B. Coley lecture
      was delivered by Lieping Chen, one of the four recipients of the 2014 William B.
      Coley Award for Distinguished Research in Tumor Immunology; the other three
      recipients were Gordon Freeman, Tasuku Honjo, and Arlene Sharpe. Prominent themes
      of the conference were the use of genomic technologies to identify neoantigens
      and the emergence of new immune modulatory molecules, beyond CTLA-4 and PD-1/PD
      L1, as new therapeutic targets for immunotherapy.

PMID- 25941355
TI  - The interplay of immunotherapy and chemotherapy: harnessing potential synergies.
AB  - Although cancer chemotherapy has historically been considered immune suppressive,
      it is now accepted that certain chemotherapies can augment tumor immunity. The
      recent success of immune checkpoint inhibitors has renewed interest in
      immunotherapies, and in combining them with chemotherapy to achieve additive or
      synergistic clinical activity. Two major ways that chemotherapy promotes tumor
      immunity are by inducing immunogenic cell death as part of its intended
      therapeutic effect and by disrupting strategies that tumors use to evade immune
      recognition. This second strategy, in particular, is dependent on the drug, its
      dose, and the schedule of chemotherapy administration in relation to antigen
      exposure or release. In this Cancer Immunology at the Crossroads article, we
      focus on cancer vaccines and immune checkpoint blockade as a forum for reviewing
      preclinical and clinical data demonstrating the interplay between immunotherapy
      and chemotherapy.

PMID- 25941357
TI  - Serial Killers and Mass Murderers: Engineered T Cells Are up to the Task.

PMID- 25941354
TI  - The regulatory role of invariant NKT cells in tumor immunity.
AB  - Invariant natural killer T (iNKT) cells are a unique population of T lymphocytes,
      which lie at the interface between the innate and adaptive immune systems, and
      are important mediators of immune responses and tumor surveillance. iNKT cells
      recognize lipid antigens in a CD1d-dependent manner; their subsequent activation
      results in a rapid and specific downstream response, which enhances both innate
      and adaptive immunity. The capacity of iNKT cells to modify the immune
      microenvironment influences the ability of the host to control tumor growth,
      making them an important population to be harnessed in the clinic for the
      development of anticancer therapeutics. Indeed, the identification of strong iNKT
      cell agonists, such as alpha-galactosylceramide (alpha-GalCer) and its analogues,
      has led to the development of synthetic lipids that have shown potential in
      vaccination and treatment against cancers. In this Masters of Immunology article,
      we discuss these latest findings and summarize the major discoveries in iNKT-cell
      biology, which have enabled the design of potent strategies for immune-mediated
      tumor destruction.

PMID- 25941358
TI  - Neuronal thresholds and choice-related activity of otolith afferent fibers during
      heading perception.
AB  - How activity of sensory neurons leads to perceptual decisions remains a challenge
      to understand. Correlations between choices and single neuron firing rates have
      been found early in vestibular processing, in the brainstem and cerebellum. To
      investigate the origins of choice-related activity, we have recorded from otolith
      afferent fibers while animals performed a fine heading discrimination task. We
      find that afferent fibers have similar discrimination thresholds as central
      cells, and the most sensitive fibers have thresholds that are only twofold or
      threefold greater than perceptual thresholds. Unlike brainstem and cerebellar
      nuclei neurons, spike counts from afferent fibers do not exhibit trial-by-trial
      correlations with perceptual decisions. This finding may reflect the fact that
      otolith afferent responses are poorly suited for driving heading perception
      because they fail to discriminate self-motion from changes in orientation
      relative to gravity. Alternatively, if choice probabilities reflect top-down
      inference signals, they are not relayed to the vestibular periphery. 

PMID- 25941360
TI  - Myocardial pressure overload induces systemic inflammation through endothelial
      cell IL-33.
AB  - Hypertension increases the pressure load on the heart and is associated with a
      poorly understood chronic systemic inflammatory state. Interleukin 33 (IL-33)
      binds to membrane-bound ST2 (ST2L) and has antihypertrophic and antifibrotic
      effects in the myocardium. In contrast, soluble ST2 appears to act as a decoy
      receptor for IL-33, blocking myocardial and vascular benefits, and is a
      prognostic biomarker in patients with cardiovascular diseases. Here we report
      that a highly local intramyocardial IL-33/ST2 conversation regulates the heart's
      response to pressure overload. Either endothelial-specific deletion of IL33 or
      cardiomyocyte-specific deletion of ST2 exacerbated cardiac hypertrophy with
      pressure overload. Furthermore, pressure overload induced systemic circulating IL
      33 as well as systemic circulating IL-13 and TGF-beta1; this was abolished by
      endothelial-specific deletion of IL33 but not by cardiomyocyte-specific deletion
      of IL33. Our study reveals that endothelial cell secretion of IL-33 is crucial
      for translating myocardial pressure overload into a selective systemic
      inflammatory response. 

PMID- 25941361
TI  - Supplementary feeding restructures urban bird communities.
AB  - Food availability is a primary driver of avian population regulation. However,
      few studies have considered the effects of what is essentially a massive
      supplementary feeding experiment: the practice of wild bird feeding. Bird feeding
      has been posited as an important factor influencing the structure of bird
      communities, especially in urban areas, although experimental evidence to support
      this is almost entirely lacking. We carried out an 18-mo experimental feeding
      study at 23 residential properties to investigate the effects of bird feeding on
      local urban avian assemblages. Our feeding regime was based on predominant urban
      feeding practices in our region. We used monthly bird surveys to compare avian
      community composition, species richness, and the densities of local species at
      feeding and nonfeeding properties. Avian community structure diverged at feeding
      properties and five of the commonest garden bird species were affected by the
      experimental feeding regime. Introduced birds particularly benefitted, with
      dramatic increases observed in the abundances of house sparrow (Passer
      domesticus) and spotted dove (Streptopelia chinensis) in particular. We also
      found evidence of a negative effect on the abundance of a native insectivore, the
      grey warbler (Gerygone igata). Almost all of the observed changes did not persist
      once feeding had ceased. Our study directly demonstrates that the human pastime
      of bird feeding substantially contributes to the structure of avian community in
      urban areas, potentially altering the balance between native and introduced
      species. 

PMID- 25941359
TI  - Interleukin-6/interleukin-21 signaling axis is critical in the pathogenesis of
      pulmonary arterial hypertension.
AB  - IL-6 is a multifunctional proinflammatory cytokine that is elevated in the serum
      of patients with pulmonary arterial hypertension (PAH) and can predict the
      survival of patients with idiopathic PAH (IPAH). Previous animal experiments and
      clinical human studies indicate that IL-6 is important in PAH; however, the
      molecular mechanisms of IL-6-mediated pathogenesis of PAH have been elusive. Here
      we identified IL-21 as a downstream target of IL-6 signaling in PAH. First, we
      found that IL-6 blockade by the monoclonal anti-IL-6 receptor antibody, MR16-1,
      ameliorated hypoxia-induced pulmonary hypertension (HPH) and prevented the
      hypoxia-induced accumulation of Th17 cells and M2 macrophages in the lungs.
      Consistently, the expression levels of IL-17 and IL-21 genes, one of the
      signature genes for Th17 cells, were significantly up-regulated after hypoxia
      exposure in the lungs of mice treated with control antibody but not in the lungs
      of mice treated with MR16-1. Although IL-17 blockade with an anti-IL-17A
      neutralizing antibody had no effect on HPH, IL-21 receptor-deficient mice were
      resistant to HPH and exhibited no significant accumulation of M2 macrophages in
      the lungs. In accordance with these findings, IL-21 promoted the polarization of
      primary alveolar macrophages toward the M2 phenotype. Of note, significantly
      enhanced expressions of IL-21 and M2 macrophage markers were detected in the
      lungs of IPAH patients who underwent lung transplantation. Collectively, these
      findings suggest that IL-21 promotes PAH in association with M2 macrophage
      polarization, downstream of IL-6-signaling. The IL-6/IL-21-signaling axis may be
      a potential target for treating PAH. 

PMID- 25941363
TI  - Cahokia's emergence and decline coincided with shifts of flood frequency on the
      Mississippi River.
AB  - Here we establish the timing of major flood events of the central Mississippi
      River over the last 1,800 y, using floodwater sediments deposited in two
      floodplain lakes. Shifts in the frequency of high-magnitude floods are mediated
      by moisture availability over midcontinental North America and correspond to the
      emergence and decline of Cahokia--a major late prehistoric settlement in the
      Mississippi River floodplain. The absence of large floods from A.D. 600 to A.D.
      1200 facilitated agricultural intensification, population growth, and settlement
      expansion across the floodplain that are associated with the emergence of Cahokia
      as a regional center around A.D. 1050. The return of large floods after A.D.
      1200, driven by waning midcontinental aridity, marks the onset of sociopolitical
      reorganization and depopulation that culminate in the abandonment of Cahokia and
      the surrounding region by A.D. 1350. Shifts in the frequency and magnitude of
      flooding may be an underappreciated but critical factor in the formation and
      dissolution of social complexity in early agricultural societies.

PMID- 25941362
TI  - Role of a ribosomal RNA phosphate oxygen during the EF-G-triggered GTP
      hydrolysis.
AB  - Elongation factor-catalyzed GTP hydrolysis is a key reaction during the ribosomal
      elongation cycle. Recent crystal structures of G proteins, such as elongation
      factor G (EF-G) bound to the ribosome, as well as many biochemical studies,
      provide evidence that the direct interaction of translational GTPases (trGTPases)
      with the sarcin-ricin loop (SRL) of ribosomal RNA (rRNA) is pivotal for
      hydrolysis. However, the precise mechanism remains elusive and is intensively
      debated. Based on the close proximity of the phosphate oxygen of A2662 of the SRL
      to the supposedly catalytic histidine of EF-G (His87), we probed this interaction
      by an atomic mutagenesis approach. We individually replaced either of the two
      nonbridging phosphate oxygens at A2662 with a methyl group by the introduction of
      a methylphosphonate instead of the natural phosphate in fully functional,
      reconstituted bacterial ribosomes. Our major finding was that only one of the two
      resulting diastereomers, the SP methylphosphonate, was compatible with efficient
      GTPase activation on EF-G. The same trend was observed for a second trGTPase,
      namely EF4 (LepA). In addition, we provide evidence that the negative charge of
      the A2662 phosphate group must be retained for uncompromised activity in GTP
      hydrolysis. In summary, our data strongly corroborate that the nonbridging proSP
      phosphate oxygen at the A2662 of the SRL is critically involved in the activation
      of GTP hydrolysis. A mechanistic scenario is supported in which positioning of
      the catalytically active, protonated His87 through electrostatic interactions
      with the A2662 phosphate group and H-bond networks are key features of ribosome
      triggered activation of trGTPases. 

PMID- 25941364
TI  - Differential effects of fructose versus glucose on brain and appetitive responses
      to food cues and decisions for food rewards.
AB  - Prior studies suggest that fructose compared with glucose may be a weaker
      suppressor of appetite, and neuroimaging research shows that food cues trigger
      greater brain reward responses in a fasted relative to a fed state. We sought to
      determine the effects of ingesting fructose versus glucose on brain, hormone, and
      appetitive responses to food cues and food-approach behavior. Twenty-four healthy
      volunteers underwent two functional magnetic resonance imaging (fMRI) sessions
      with ingestion of either fructose or glucose in a double-blinded, random-order
      cross-over design. fMRI was performed while participants viewed images of high
      calorie foods and nonfood items using a block design. After each block,
      participants rated hunger and desire for food. Participants also performed a
      decision task in which they chose between immediate food rewards and delayed
      monetary bonuses. Hormones were measured at baseline and 30 and 60 min after
      drink ingestion. Ingestion of fructose relative to glucose resulted in smaller
      increases in plasma insulin levels and greater brain reactivity to food cues in
      the visual cortex (in whole-brain analysis) and left orbital frontal cortex (in
      region-of-interest analysis). Parallel to the neuroimaging findings, fructose
      versus glucose led to greater hunger and desire for food and a greater
      willingness to give up long-term monetary rewards to obtain immediate high
      calorie foods. These findings suggest that ingestion of fructose relative to
      glucose results in greater activation of brain regions involved in attention and
      reward processing and may promote feeding behavior. 

PMID- 25941365
TI  - Modeling malaria genomics reveals transmission decline and rebound in Senegal.
AB  - To study the effects of malaria-control interventions on parasite population
      genomics, we examined a set of 1,007 samples of the malaria parasite Plasmodium
      falciparum collected in Thies, Senegal between 2006 and 2013. The parasite
      samples were genotyped using a molecular barcode of 24 SNPs. About 35% of the
      samples grouped into subsets with identical barcodes, varying in size by year and
      sometimes persisting across years. The barcodes also formed networks of related
      groups. Analysis of 164 completely sequenced parasites revealed extensive sharing
      of genomic regions. In at least two cases we found first-generation recombinant
      offspring of parents whose genomes are similar or identical to genomes also
      present in the sample. An epidemiological model that tracks parasite genotypes
      can reproduce the observed pattern of barcode subsets. Quantification of
      likelihoods in the model strongly suggests a reduction of transmission from 2006
      2010 with a significant rebound in 2012-2013. The reduced transmission and
      rebound were confirmed directly by incidence data from Thies. These findings
      imply that intensive intervention to control malaria results in rapid and
      dramatic changes in parasite population genomics. The results also suggest that
      genomics combined with epidemiological modeling may afford prompt, continuous,
      and cost-effective tracking of progress toward malaria elimination. 

PMID- 25941366
TI  - Persistent ecological shifts in marine molluscan assemblages across the end
      Cretaceous mass extinction.
AB  - Contemporary biodiversity loss and population declines threaten to push the
      biosphere toward a tipping point with irreversible effects on ecosystem
      composition and function. As a potential example of a global-scale regime shift
      in the geological past, we assessed ecological changes across the end-Cretaceous
      mass extinction based on molluscan assemblages at four well-studied sites. By
      contrasting preextinction and postextinction rank abundance and numerical
      abundance in 19 molluscan modes of life--each defined as a unique combination of
      mobility level, feeding mode, and position relative to the substrate--we find
      distinct shifts in ecospace utilization, which significantly exceed predictions
      from null models. The magnitude of change in functional traits relative to normal
      temporal fluctuations at far-flung sites indicates that molluscan assemblages
      shifted to differently structured systems and faunal response was global. The
      strengths of temporal ecological shifts, however, are mostly within the range of
      preextinction site-to-site variability, demonstrating that local ecological
      turnover was similar to geographic variation over a broad latitudinal range. In
      conjunction with varied site-specific temporal patterns of individual modes of
      life, these spatial and temporal heterogeneities argue against a concerted phase
      shift of molluscan assemblages from one well-defined regime to another. At a
      broader ecological level, by contrast, congruent tendencies emerge and suggest
      deterministic processes. These patterns comprise the well-known increase of
      deposit-feeding mollusks in postextinction assemblages and increases in predators
      and predator-resistant modes of life, i.e., those characterized by elevated
      mobility and infaunal life habits.

PMID- 25941368
TI  - The phototransduction machinery in the rod outer segment has a strong efficacy
      gradient.
AB  - Rod photoreceptors consist of an outer segment (OS) and an inner segment. Inside
      the OS a biochemical machinery transforms the rhodopsin photoisomerization into
      electrical signal. This machinery has been treated as and is thought to be
      homogenous with marginal inhomogeneities. To verify this assumption, we developed
      a methodology based on special tapered optical fibers (TOFs) to deliver highly
      localized light stimulations. By using these TOFs, specific regions of the rod OS
      could be stimulated with spots of light highly confined in space. As the TOF is
      moved from the OS base toward its tip, the amplitude of saturating and single
      photon responses decreases, demonstrating that the efficacy of the transduction
      machinery is not uniform and is 5-10 times higher at the base than at the tip.
      This gradient of efficacy of the transduction machinery is attributed to a
      progressive depletion of the phosphodiesterase along the rod OS. Moreover we
      demonstrate that, using restricted spots of light, the duration of the
      photoresponse along the OS does not increase linearly with the light intensity as
      with diffuse light. 

PMID- 25941369
TI  - Age-related changes in working memory and the ability to ignore distraction.
AB  - A weakened ability to effectively resist distraction is a potential basis for
      reduced working memory capacity (WMC) associated with healthy aging. Exploiting
      data from 29,631 users of a smartphone game, we show that, as age increases,
      working memory (WM) performance is compromised more by distractors presented
      during WM maintenance than distractors presented during encoding. However, with
      increasing age, the ability to exclude distraction at encoding is a better
      predictor of WMC in the absence of distraction. A significantly greater
      contribution of distractor filtering at encoding represents a potential
      compensation for reduced WMC in older age. 

PMID- 25941367
TI  - CD4 mimetics sensitize HIV-1-infected cells to ADCC.
AB  - HIV-1-infected cells presenting envelope glycoproteins (Env) in the CD4-bound
      conformation on their surface are preferentially targeted by antibody-dependent
      cell-mediated cytotoxicity (ADCC). HIV-1 has evolved a sophisticated mechanism to
      avoid exposure of ADCC-mediating Env epitopes by down-regulating CD4 and by
      limiting the overall amount of Env at the cell surface. Here we report that small
      molecule CD4-mimetic compounds induce the CD4-bound conformation of Env, and
      thereby sensitize cells infected with primary HIV-1 isolates to ADCC mediated by
      antibodies present in sera, cervicovaginal lavages, and breast milk from HIV-1
      infected individuals. Importantly, we identified one CD4 mimetic with the
      capacity to sensitize endogenously infected ex vivo-amplified primary CD4 T cells
      to ADCC killing mediated by autologous sera and effector cells. Thus, CD4
      mimetics hold the promise of therapeutic utility in preventing and controlling
      HIV-1 infection. 

PMID- 25941371
TI  - Metabolic dependencies drive species co-occurrence in diverse microbial
      communities.
AB  - Microbial communities populate most environments on earth and play a critical
      role in ecology and human health. Their composition is thought to be largely
      shaped by interspecies competition for the available resources, but cooperative
      interactions, such as metabolite exchanges, have also been implicated in
      community assembly. The prevalence of metabolic interactions in microbial
      communities, however, has remained largely unknown. Here, we systematically
      survey, by using a genome-scale metabolic modeling approach, the extent of
      resource competition and metabolic exchanges in over 800 communities. We find
      that, despite marked resource competition at the level of whole assemblies,
      microbial communities harbor metabolically interdependent groups that recur
      across diverse habitats. By enumerating flux-balanced metabolic exchanges in
      these co-occurring subcommunities we also predict the likely exchanged
      metabolites, such as amino acids and sugars, that can promote group survival
      under nutritionally challenging conditions. Our results highlight metabolic
      dependencies as a major driver of species co-occurrence and hint at cooperative
      groups as recurring modules of microbial community architecture. 

PMID- 25941370
TI  - Lack of pairing during meiosis triggers multigenerational transgene silencing in
      Caenorhabditis elegans.
AB  - Single-copy transgenes in Caenorhabditis elegans can be subjected to a potent,
      irreversible silencing process termed small RNA-induced epigenetic silencing
      (RNAe). RNAe is promoted by the Piwi Argonaute protein PRG-1 and associated Piwi
      interacting RNAs (piRNAs), as well as by proteins that promote and respond to
      secondary small interfering RNA (siRNA) production. Here we define a related
      siRNA-mediated silencing process, termed "multigenerational RNAe," which can
      occur for transgenes that are maintained in a hemizygous state for several
      generations. We found that transgenes that contain either GFP or mCherry epitope
      tags can be silenced via multigenerational RNAe, whereas a transgene that
      possesses GFP and a perfect piRNA target site can be rapidly and permanently
      silenced via RNAe. Although previous studies have shown that PRG-1 is typically
      dispensable for maintenance of RNAe, we found that both initiation and
      maintenance of multigenerational RNAe requires PRG-1 and the secondary siRNA
      biogenesis protein RDE-2. Although silencing via RNAe is irreversible, we found
      that transgene expression can be restored when hemizygous transgenes that were
      silenced via multigenerational RNAe become homozygous. Furthermore,
      multigenerational RNAe was accelerated when meiotic pairing of the chromosome
      possessing the transgene was abolished. We propose that persistent lack of
      pairing during meiosis elicits a reversible multigenerational silencing response,
      which can lead to permanent transgene silencing. Multigenerational RNAe may be
      broadly relevant to single-copy transgenes used in experimental biology and to
      shaping the epigenomic landscape of diverse species, where genomic polymorphisms
      between homologous chromosomes commonly result in unpaired DNA during meiosis. 

PMID- 25941372
TI  - Stable long-range interhemispheric coordination is supported by direct anatomical
      projections.
AB  - The functional interaction between the brain's two hemispheres includes a unique
      set of connections between corresponding regions in opposite hemispheres (i.e.,
      homotopic regions) that are consistently reported to be exceptionally strong
      compared with other interhemispheric (i.e., heterotopic) connections. The
      strength of homotopic functional connectivity (FC) is thought to be mediated by
      the regions' shared functional roles and their structural connectivity. Recently,
      homotopic FC was reported to be stable over time despite the presence of dynamic
      FC across both intrahemispheric and heterotopic connections. Here we build on
      this work by considering whether homotopic FC is also stable across conditions.
      We additionally test the hypothesis that strong and stable homotopic FC is
      supported by the underlying structural connectivity. Consistent with previous
      findings, interhemispheric FC between homotopic regions were significantly
      stronger in both humans and macaques. Across conditions, homotopic FC was most
      resistant to change and therefore was more stable than heterotopic or
      intrahemispheric connections. Across time, homotopic FC had significantly greater
      temporal stability than other types of connections. Temporal stability of
      homotopic FC was facilitated by direct anatomical projections. Importantly,
      temporal stability varied with the change in conductive properties of callosal
      axons along the anterior-posterior axis. Taken together, these findings suggest a
      notable role for the corpus callosum in maintaining stable functional
      communication between hemispheres. 

PMID- 25941373
TI  - Self-motion perception in autism is compromised by visual noise but integrated
      optimally across multiple senses.
AB  - Perceptual processing in autism spectrum disorder (ASD) is marked by superior low
      level task performance and inferior complex-task performance. This observation
      has led to theories of defective integration in ASD of local parts into a global
      percept. Despite mixed experimental results, this notion maintains widespread
      influence and has also motivated recent theories of defective multisensory
      integration in ASD. Impaired ASD performance in tasks involving classic random
      dot visual motion stimuli, corrupted by noise as a means to manipulate task
      difficulty, is frequently interpreted to support this notion of global
      integration deficits. By manipulating task difficulty independently of visual
      stimulus noise, here we test the hypothesis that heightened sensitivity to noise,
      rather than integration deficits, may characterize ASD. We found that although
      perception of visual motion through a cloud of dots was unimpaired without noise,
      the addition of stimulus noise significantly affected adolescents with ASD, more
      than controls. Strikingly, individuals with ASD demonstrated intact multisensory
      (visual-vestibular) integration, even in the presence of noise. Additionally,
      when vestibular motion was paired with pure visual noise, individuals with ASD
      demonstrated a different strategy than controls, marked by reduced flexibility.
      This result could be simulated by using attenuated (less reliable) and inflexible
      (not experience-dependent) Bayesian priors in ASD. These findings question
      widespread theories of impaired global and multisensory integration in ASD.
      Rather, they implicate increased sensitivity to sensory noise and less use of
      prior knowledge in ASD, suggesting increased reliance on incoming sensory
      information. 

PMID- 25941374
TI  - Sequence type 1 group B Streptococcus, an emerging cause of invasive disease in
      adults, evolves by small genetic changes.
AB  - The molecular mechanisms underlying pathogen emergence in humans is a critical
      but poorly understood area of microbiologic investigation. Serotype V group B
      Streptococcus (GBS) was first isolated from humans in 1975, and rates of invasive
      serotype V GBS disease significantly increased starting in the early 1990s. We
      found that 210 of 229 serotype V GBS strains (92%) isolated from the bloodstream
      of nonpregnant adults in the United States and Canada between 1992 and 2013 were
      multilocus sequence type (ST) 1. Elucidation of the complete genome of a 1992 ST
      1 strain revealed that this strain had the highest homology with a GBS strain
      causing cow mastitis and that the 1992 ST-1 strain differed from serotype V
      strains isolated in the late 1970s by acquisition of cell surface proteins and
      antimicrobial resistance determinants. Whole-genome comparison of 202 invasive ST
      1 strains detected significant recombination in only eight strains. The remaining
      194 strains differed by an average of 97 SNPs. Phylogenetic analysis revealed a
      temporally dependent mode of genetic diversification consistent with the
      emergence in the 1990s of ST-1 GBS as major agents of human disease. Thirty-one
      loci were identified as being under positive selective pressure, and mutations at
      loci encoding polysaccharide capsule production proteins, regulators of pilus
      expression, and two-component gene regulatory systems were shown to affect the
      bacterial phenotype. These data reveal that phenotypic diversity among ST-1 GBS
      is mainly driven by small genetic changes rather than extensive recombination,
      thereby extending knowledge into how pathogens adapt to humans. 

PMID- 25941375
TI  - Single-cell mass spectrometry reveals small molecules that affect cell fates in
      the 16-cell embryo.
AB  - Spatial and temporal changes in molecular expression are essential to embryonic
      development, and their characterization is critical to understand mechanisms by
      which cells acquire different phenotypes. Although technological advances have
      made it possible to quantify expression of large molecules during embryogenesis,
      little information is available on metabolites, the ultimate indicator of
      physiological activity of the cell. Here, we demonstrate that single-cell
      capillary electrophoresis-electrospray ionization mass spectrometry is able to
      test whether differential expression of the genome translates to the domain of
      metabolites between single embryonic cells. Dissection of three different cell
      types with distinct tissue fates from 16-cell embryos of the South African clawed
      frog (Xenopus laevis) and microextraction of their metabolomes enabled the
      identification of 40 metabolites that anchored interconnected central metabolic
      networks. Relative quantitation revealed that several metabolites were
      differentially active between the cell types in the wild-type, unperturbed
      embryos. Altering postfertilization cytoplasmic movements that perturb dorsal
      development confirmed that these three cells have characteristic small-molecular
      activity already at cleavage stages as a result of cell type and not differences
      in pigmentation, yolk content, cell size, or position in the embryo. Changing the
      metabolite concentration caused changes in cell movements at gastrulation that
      also altered the tissue fates of these cells, demonstrating that the metabolome
      affects cell phenotypes in the embryo. 

PMID- 25941376
TI  - Specific heat and sound velocity at the relevant competing phase of high
      temperature superconductors.
AB  - Recent highly accurate sound velocity measurements reveal a phase transition to a
      competing phase in YBa2Cu3O6+delta that is not identified in available specific
      heat measurements. We show that this signature is consistent with the
      universality class of the loop current-ordered state when the free-energy
      reduction is similar to the superconducting condensation energy, due to the
      anomalous fluctuation region of such a transition. We also compare the measured
      specific heat with some usual types of transitions, which are observed at lower
      temperatures in some cuprates, and find that the upper limit of the energy
      reduction due to them is about 1/40th the superconducting condensation energy. 

PMID- 25941377
TI  - Tempo and mode of antibat ultrasound production and sonar jamming in the diverse
      hawkmoth radiation.
AB  - The bat-moth arms race has existed for over 60 million y, with moths evolving
      ultrasonically sensitive ears and ultrasound-producing organs to combat bat
      predation. The evolution of these defenses has never been thoroughly examined
      because of limitations in simultaneously conducting behavioral and phylogenetic
      analyses across an entire group. Hawkmoths include >1,500 species worldwide, some
      of which produce ultrasound using genital stridulatory structures. However, the
      function and evolution of this behavior remain largely unknown. We built a
      comprehensive behavioral dataset of hawkmoth hearing and ultrasonic reply to
      sonar attack using high-throughput field assays. Nearly half of the species
      tested (57 of 124 species) produced ultrasound to tactile stimulation or playback
      of bat echolocation attack. To test the function of ultrasound, we pitted big
      brown bats (Eptesicus fuscus) against hawkmoths over multiple nights and show
      that hawkmoths jam bat sonar. Ultrasound production was immediately and
      consistently effective at thwarting attack and bats regularly performed catching
      behavior without capturing moths. We also constructed a fossil-calibrated,
      multigene phylogeny to study the evolutionary history and divergence times of
      these antibat strategies across the entire family. We show that ultrasound
      production arose in multiple groups, starting in the late Oligocene (~ 26 Ma)
      after the emergence of insectivorous bats. Sonar jamming and bat-detecting ears
      arose twice, independently, in the Miocene (18-14 Ma) either from earless
      hawkmoths that produced ultrasound in response to physical contact only, or from
      species that did not respond to touch or bat echolocation attack.

PMID- 25941378
TI  - Dictyostelium discoideum has a highly Q/N-rich proteome and shows an unusual
      resilience to protein aggregation.
AB  - Many protein-misfolding diseases are caused by proteins carrying prion-like
      domains. These proteins show sequence similarity to yeast prion proteins, which
      can interconvert between an intrinsically disordered and an aggregated prion
      state. The natural presence of prions in yeast has provided important insight
      into disease mechanisms and cellular proteostasis. However, little is known about
      prions in other organisms, and it is not yet clear whether the findings in yeast
      can be generalized. Using bioinformatics tools, we show that Dictyostelium
      discoideum has the highest content of prion-like proteins of all organisms
      investigated to date, suggesting that its proteome has a high overall aggregation
      propensity. To study mechanisms regulating these proteins, we analyze the
      behavior of several well-characterized prion-like proteins, such as an expanded
      version of human huntingtin exon 1 (Q103) and the prion domain of the yeast prion
      protein Sup35 (NM), in D. discoideum. We find that these proteins remain soluble
      and are innocuous to D. discoideum, in contrast to other organisms, where they
      form cytotoxic cytosolic aggregates. However, when exposed to conditions that
      compromise molecular chaperones, these proteins aggregate and become cytotoxic.
      We show that the disaggregase Hsp101, a molecular chaperone of the Hsp100 family,
      dissolves heat-induced aggregates and promotes thermotolerance. Furthermore,
      prion-like proteins accumulate in the nucleus, where they are targeted by the
      ubiquitin-proteasome system. Our data suggest that D. discoideum has undergone
      specific adaptations that increase the proteostatic capacity of this organism and
      allow for an efficient regulation of its prion-like proteome. 

PMID- 25941380
TI  - Elastocapillary interactions on nematic films.
AB  - Rod-like colloids distort fluid interfaces and interact by capillarity. We
      explore this interaction at the free surface of aligned nematic liquid crystal
      films. Naive comparison of capillary and elastic energies suggests that particle
      assembly would be determined solely by surface tension. Here, we demonstrate
      that, under certain circumstances, the capillary and elastic effects are
      complementary and each plays an important role. Particles assemble end-to-end, as
      dictated by capillarity, and align along the easy axis of the director field, as
      dictated by elasticity. On curved fluid interfaces, however, curvature capillary
      energies can overcome the elastic orientations and drive particle migration along
      curvature gradients. Domains of dominant interaction and their transition are
      investigated. 

PMID- 25941379
TI  - Extreme selective sweeps independently targeted the X chromosomes of the great
      apes.
AB  - The unique inheritance pattern of the X chromosome exposes it to natural
      selection in a way that is different from that of the autosomes, potentially
      resulting in accelerated evolution. We perform a comparative analysis of X
      chromosome polymorphism in 10 great ape species, including humans. In most
      species, we identify striking megabase-wide regions, where nucleotide diversity
      is less than 20% of the chromosomal average. Such regions are found exclusively
      on the X chromosome. The regions overlap partially among species, suggesting that
      the underlying targets are partly shared among species. The regions have higher
      proportions of singleton SNPs, higher levels of population differentiation, and a
      higher nonsynonymous-to-synonymous substitution ratio than the rest of the X
      chromosome. We show that the extent to which diversity is reduced is incompatible
      with direct selection or the action of background selection and soft selective
      sweeps alone, and therefore, we suggest that very strong selective sweeps have
      independently targeted these specific regions in several species. The only
      genomic feature that we can identify as strongly associated with loss of
      diversity is the location of testis-expressed ampliconic genes, which also have
      reduced diversity around them. We hypothesize that these genes may be responsible
      for selective sweeps in the form of meiotic drive caused by an intragenomic
      conflict in male meiosis. 

PMID- 25941381
TI  - G-protein betagamma subunits are positive regulators of Kv7.4 and native vascular
      Kv7 channel activity.
AB  - Kv7.4 channels are a crucial determinant of arterial diameter both at rest and in
      response to endogenous vasodilators. However, nothing is known about the factors
      that ensure effective activity of these channels. We report that G-protein
      betagamma subunits increase the amplitude and activation rate of whole-cell
      voltage-dependent K(+) currents sensitive to the Kv7 blocker linopirdine in HEK
      cells heterologously expressing Kv7.4, and in rat renal artery myocytes. In
      excised patch recordings, Gbetagamma subunits (2-250 ng /mL) enhanced the open
      probability of Kv7.4 channels without changing unitary conductance. Kv7 channel
      activity was also augmented by stimulation of G-protein-coupled receptors.
      Gallein, an inhibitor of Gbetagamma subunits, prevented these stimulatory
      effects. Moreover, gallein and two other structurally different Gbetagamma
      subunit inhibitors (GRK2i and a beta-subunit antibody) abolished Kv7 channel
      currents in the absence of either Gbetagamma subunit enrichment or G-protein
      coupled receptor stimulation. Proximity ligation assay revealed that Kv7.4 and
      Gbetagamma subunits colocalized in HEK cells and renal artery smooth muscle
      cells. Gallein disrupted this colocalization, contracted whole renal arteries to
      a similar degree as the Kv7 inhibitor linopirdine, and impaired isoproterenol
      induced relaxations. Furthermore, mSIRK, which disassociates Gbetagamma subunits
      from alpha subunits without stimulating nucleotide exchange, relaxed
      precontracted arteries in a linopirdine-sensitive manner. These results reveal
      that Gbetagamma subunits are fundamental for Kv7.4 activation and crucial for
      vascular Kv7 channel activity, which has major consequences for the regulation of
      arterial tone. 

PMID- 25941382
TI  - Bestrophin 1 is indispensable for volume regulation in human retinal pigment
      epithelium cells.
AB  - In response to cell swelling, volume-regulated anion channels (VRACs) participate
      in a process known as regulatory volume decrease (RVD). Only recently, first
      insight into the molecular identity of mammalian VRACs was obtained by the
      discovery of the leucine-rich repeats containing 8A (LRRC8A) gene. Here, we show
      that bestrophin 1 (BEST1) but not LRRC8A is crucial for volume regulation in
      human retinal pigment epithelium (RPE) cells. Whole-cell patch-clamp recordings
      in RPE derived from human-induced pluripotent stem cells (hiPSC) exhibit an
      outwardly rectifying chloride current with characteristic functional properties
      of VRACs. This current is severely reduced in hiPSC-RPE cells derived from
      macular dystrophy patients with pathologic BEST1 mutations. Disruption of the
      orthologous mouse gene (Best1(-/-)) does not result in obvious retinal pathology
      but leads to a severe subfertility phenotype in agreement with minor endogenous
      expression of Best1 in murine RPE but highly abundant expression in mouse testis.
      Sperm from Best1(-/-) mice showed reduced motility and abnormal sperm morphology,
      indicating an inability in RVD. Together, our data suggest that the molecular
      identity of VRACs is more complex--that is, instead of a single ubiquitous
      channel, VRACs could be formed by cell type- or tissue-specific subunit
      composition. Our findings provide the basis to further examine VRAC diversity in
      normal and diseased cell physiology, which is key to exploring novel therapeutic
      approaches in VRAC-associated pathologies.

PMID- 25941383
TI  - Electric-field-induced assembly and propulsion of chiral colloidal clusters.
AB  - Chiral molecules with opposite handedness exhibit distinct physical, chemical, or
      biological properties. They pose challenges as well as opportunities in
      understanding the phase behavior of soft matter, designing enantioselective
      catalysts, and manufacturing single-handed pharmaceuticals. Microscopic
      particles, arranged in a chiral configuration, could also exhibit unusual
      optical, electric, or magnetic responses. Here we report a simple method to
      assemble achiral building blocks, i.e., the asymmetric colloidal dimers, into a
      family of chiral clusters. Under alternating current electric fields, two to four
      lying dimers associate closely with a central standing dimer and form both right-
      and left-handed clusters on a conducting substrate. The cluster configuration is
      primarily determined by the induced dipolar interactions between constituent
      dimers. Our theoretical model reveals that in-plane dipolar repulsion between
      petals in the cluster favors the achiral configuration, whereas out-of-plane
      attraction between the central dimer and surrounding petals favors a chiral
      arrangement. It is the competition between these two interactions that dictates
      the final configuration. The theoretical chirality phase diagram is found to be
      in excellent agreement with experimental observations. We further demonstrate
      that the broken symmetry in chiral clusters induces an unbalanced
      electrohydrodynamic flow surrounding them. As a result, they rotate in opposite
      directions according to their handedness. Both the assembly and propulsion
      mechanisms revealed here can be potentially applied to other types of asymmetric
      particles. Such kinds of chiral colloids will be useful for fabricating
      metamaterials, making model systems for both chiral molecules and active matter,
      or building propellers for microscale transport. 

PMID- 25941384
TI  - Sample and population exponents of generalized Taylor's law.
AB  - Taylor's law (TL) states that the variance V of a nonnegative random variable is
      a power function of its mean M; i.e., V = aM(b). TL has been verified extensively
      in ecology, where it applies to population abundance, physics, and other natural
      sciences. Its ubiquitous empirical verification suggests a context-independent
      mechanism. Sample exponents b measured empirically via the scaling of sample mean
      and variance typically cluster around the value b = 2. Some theoretical models of
      population growth, however, predict a broad range of values for the population
      exponent b pertaining to the mean and variance of population density, depending
      on details of the growth process. Is the widely reported sample exponent b ? 2
      the result of ecological processes or could it be a statistical artifact? Here,
      we apply large deviations theory and finite-sample arguments to show exactly that
      in a broad class of growth models the sample exponent is b ? 2 regardless of the
      underlying population exponent. We derive a generalized TL in terms of sample and
      population exponents b(jk) for the scaling of the kth vs. the jth cumulants. The
      sample exponent b(jk) depends predictably on the number of samples and for finite
      samples we obtain b(jk) ? k = j asymptotically in time, a prediction that we
      verify in two empirical examples. Thus, the sample exponent b ? 2 may indeed be a
      statistical artifact and not dependent on population dynamics under conditions
      that we specify exactly. Given the broad class of models investigated, our
      results apply to many fields where TL is used although inadequately understood.

PMID- 25941385
TI  - Limits to adaptation along environmental gradients.
AB  - Why do species not adapt to ever-wider ranges of conditions, gradually expanding
      their ecological niche and geographic range? Gene flow across environments has
      two conflicting effects: although it increases genetic variation, which is a
      prerequisite for adaptation, gene flow may swamp adaptation to local conditions.
      In 1956, Haldane proposed that, when the environment varies across space,
      "swamping" by gene flow creates a positive feedback between low population size
      and maladaptation, leading to a sharp range margin. However, current
      deterministic theory shows that, when variance can evolve, there is no such
      limit. Using simple analytical tools and simulations, we show that genetic drift
      can generate a sharp margin to a species' range, by reducing genetic variance
      below the level needed for adaptation to spatially variable conditions. Aided by
      separation of ecological and evolutionary timescales, the identified effective
      dimensionless parameters reveal a simple threshold that predicts when adaptation
      at the range margin fails. Two observable parameters determine the threshold: (i)
      the effective environmental gradient, which can be measured by the loss of
      fitness due to dispersal to a different environment; and (ii) the efficacy of
      selection relative to genetic drift. The theory predicts sharp range margins even
      in the absence of abrupt changes in the environment. Furthermore, it implies that
      gradual worsening of conditions across a species' habitat may lead to a sudden
      range fragmentation, when adaptation to a wide span of conditions within a single
      species becomes impossible. 

PMID- 25941386
TI  - Mechanical stimulation induces formin-dependent assembly of a perinuclear actin
      rim.
AB  - Cells constantly sense and respond to mechanical signals by reorganizing their
      actin cytoskeleton. Although a number of studies have explored the effects of
      mechanical stimuli on actin dynamics, the immediate response of actin after force
      application has not been studied. We designed a method to monitor the
      spatiotemporal reorganization of actin after cell stimulation by local force
      application. We found that force could induce transient actin accumulation in the
      perinuclear region within ~ 2 min. This actin reorganization was triggered by an
      intracellular Ca(2+) burst induced by force application. Treatment with the
      calcium ionophore A23187 recapitulated the force-induced perinuclear actin
      remodeling. Blocking of actin polymerization abolished this process.
      Overexpression of Klarsicht, ANC-1, Syne Homology (KASH) domain to displace
      nesprins from the nuclear envelope did not abolish Ca(2+)-dependent perinuclear
      actin assembly. However, the endoplasmic reticulum- and nuclear membrane
      associated inverted formin-2 (INF2), a potent actin polymerization activator
      (mutations of which are associated with several genetic diseases), was found to
      be important for perinuclear actin assembly. The perinuclear actin rim structure
      colocalized with INF2 on stimulation, and INF2 depletion resulted in attenuation
      of the rim formation. Our study suggests that cells can respond rapidly to
      external force by remodeling perinuclear actin in a unique Ca(2+)- and INF2
      dependent manner.

PMID- 25941388
TI  - Rational design of self-assembly pathways for complex multicomponent structures.
AB  - The field of complex self-assembly is moving toward the design of multiparticle
      structures consisting of thousands of distinct building blocks. To exploit the
      potential benefits of structures with such "addressable complexity," we need to
      understand the factors that optimize the yield and the kinetics of self-assembly.
      Here we use a simple theoretical method to explain the key features responsible
      for the unexpected success of DNA-brick experiments, which are currently the only
      demonstration of reliable self-assembly with such a large number of components.
      Simulations confirm that our theory accurately predicts the narrow temperature
      window in which error-free assembly can occur. Even more strikingly, our theory
      predicts that correct assembly of the complete structure may require a time
      dependent experimental protocol. Furthermore, we predict that low coordination
      numbers result in nonclassical nucleation behavior, which we find to be essential
      for achieving optimal nucleation kinetics under mild growth conditions. We also
      show that, rather surprisingly, the use of heterogeneous bond energies improves
      the nucleation kinetics and in fact appears to be necessary for assembling
      certain intricate 3D structures. This observation makes it possible to sculpt
      nucleation pathways by tuning the distribution of interaction strengths. These
      insights not only suggest how to improve the design of structures based on DNA
      bricks, but also point the way toward the creation of a much wider class of
      chemical or colloidal structures with addressable complexity. 

PMID- 25941387
TI  - Multisite interaction with Sufu regulates Ci/Gli activity through distinct
      mechanisms in Hh signal transduction.
AB  - The tumor suppressor protein Suppressor of fused (Sufu) plays a conserved role in
      the Hedgehog (Hh) signaling pathway by inhibiting Cubitus interruptus (Ci)/Glioma
      associated oncogene homolog (Gli) transcription factors, but the molecular
      mechanism by which Sufu inhibits Ci/Gli activity remains poorly understood. Here
      we show that Sufu can bind Ci/Gli through a C-terminal Sufu-interacting site
      (SIC) in addition to a previously identified N-terminal site (SIN), and that both
      SIC and SIN are required for optimal inhibition of Ci/Gli by Sufu. We show that
      Sufu can sequester Ci/Gli in the cytoplasm through binding to SIN while
      inhibiting Ci/Gli activity in the nucleus depending on SIC. We also find that
      binding of Sufu to SIC and the middle region of Ci can impede recruitment of the
      transcriptional coactivator CBP by masking its binding site in the C-terminal
      region of Ci. Indeed, moving the CBP-binding site to an "exposed" location can
      render Ci resistant to Sufu-mediated inhibition in the nucleus. Hence, our study
      identifies a previously unidentified and conserved Sufu-binding motif in the C
      terminal region of Ci/Gli and provides mechanistic insight into how Sufu inhibits
      Ci/Gli activity in the nucleus. 

PMID- 25941389
TI  - Discovery of a glowing millipede in California and the gradual evolution of
      bioluminescence in Diplopoda.
AB  - The rediscovery of the Californian millipede Xystocheir bistipita surprisingly
      reveals that the species is bioluminescent. Using molecular phylogenetics, we
      show that X. bistipita is the evolutionary sister group of Motyxia, the only
      genus of New World bioluminescent millipedes. We demonstrate that bioluminescence
      originated in the group's most recent common ancestor and evolved by gradual,
      directional change through diversification. Because bioluminescence in Motyxia
      has been experimentally demonstrated to be aposematic, forewarning of the
      animal's cyanide-based toxins, these results are contrary to aposematic theory
      and empirical evidence that a warning pattern cannot evolve gradually in
      unpalatable prey. However, gradual evolution of a warning pattern is plausible if
      faint light emission served another function and was co-opted as an aposematic
      signal later in the diversification of the genus. Luminescence in Motyxia stem
      group taxa may have initially evolved to cope with reactive oxygen stress
      triggered by a hot, dry environment and was repurposed for aposematism by high
      elevation crown-group taxa colonizing new habitats with varying levels of
      predation. The discovery of bioluminescence in X. bistipita and its pivotal
      phylogenetic location provides insight into the independent and repeated
      evolution of bioluminescence across the tree of life. 

PMID- 25941390
TI  - Place recognition and heading retrieval are mediated by dissociable cognitive
      systems in mice.
AB  - A lost navigator must identify its current location and recover its facing
      direction to restore its bearings. We tested the idea that these two tasks--place
      recognition and heading retrieval--might be mediated by distinct cognitive
      systems in mice. Previous work has shown that numerous species, including young
      children and rodents, use the geometric shape of local space to regain their
      sense of direction after disorientation, often ignoring nongeometric cues even
      when they are informative. Notably, these experiments have almost always been
      performed in single-chamber environments in which there is no ambiguity about
      place identity. We examined the navigational behavior of mice in a two-chamber
      paradigm in which animals had to both recognize the chamber in which they were
      located (place recognition) and recover their facing direction within that
      chamber (heading retrieval). In two experiments, we found that mice used
      nongeometric features for place recognition, but simultaneously failed to use
      these same features for heading retrieval, instead relying exclusively on spatial
      geometry. These results suggest the existence of separate systems for place
      recognition and heading retrieval in mice that are differentially sensitive to
      geometric and nongeometric cues. We speculate that a similar cognitive
      architecture may underlie human navigational behavior.

PMID- 25941391
TI  - Specialization and integration of functional thalamocortical connectivity in the
      human infant.
AB  - Connections between the thalamus and cortex develop rapidly before birth, and
      aberrant cerebral maturation during this period may underlie a number of
      neurodevelopmental disorders. To define functional thalamocortical connectivity
      at the normal time of birth, we used functional MRI (fMRI) to measure blood
      oxygen level-dependent (BOLD) signals in 66 infants, 47 of whom were at high risk
      of neurocognitive impairment because of birth before 33 wk of gestation and 19 of
      whom were term infants. We segmented the thalamus based on correlation with
      functionally defined cortical components using independent component analysis
      (ICA) and seed-based correlations. After parcellating the cortex using ICA and
      segmenting the thalamus based on dominant connections with cortical
      parcellations, we observed a near-facsimile of the adult functional parcellation.
      Additional analysis revealed that BOLD signal in heteromodal association cortex
      typically had more widespread and overlapping thalamic representations than
      primary sensory cortex. Notably, more extreme prematurity was associated with
      increased functional connectivity between thalamus and lateral primary sensory
      cortex but reduced connectivity between thalamus and cortex in the prefrontal,
      insular and anterior cingulate regions. This work suggests that, in early
      infancy, functional integration through thalamocortical connections depends on
      significant functional overlap in the topographic organization of the thalamus
      and that the experience of premature extrauterine life modulates network
      development, altering the maturation of networks thought to support salience,
      executive, integrative, and cognitive functions. 

PMID- 25941392
TI  - Antigenic cooperation among intrahost HCV variants organized into a complex
      network of cross-immunoreactivity.
AB  - Hepatitis C virus (HCV) has the propensity to cause chronic infection. Continuous
      immune escape has been proposed as a mechanism of intrahost viral evolution
      contributing to HCV persistence. Although the pronounced genetic diversity of
      intrahost HCV populations supports this hypothesis, recent observations of long
      term persistence of individual HCV variants, negative selection increase, and
      complex dynamics of viral subpopulations during infection as well as broad cross
      immunoreactivity (CR) among variants are inconsistent with the immune-escape
      hypothesis. Here, we present a mathematical model of intrahost viral population
      dynamics under the condition of a complex CR network (CRN) of viral variants and
      examine the contribution of CR to establishing persistent HCV infection. The
      model suggests a mechanism of viral adaptation by antigenic cooperation (AC),
      with immune responses against one variant protecting other variants. AC reduces
      the capacity of the host's immune system to neutralize certain viral variants.
      CRN structure determines specific roles for each viral variant in host
      adaptation, with variants eliciting broad-CR antibodies facilitating persistence
      of other variants immunoreacting with these antibodies. The proposed mechanism is
      supported by empirical observations of intrahost HCV evolution. Interference with
      AC is a potential strategy for interruption and prevention of chronic HCV
      infection. 

PMID- 25941393
TI  - Obstruction of adaptation in diploids by recessive, strongly deleterious alleles.
AB  - Recessive deleterious mutations are common, causing many genetic disorders in
      humans and producing inbreeding depression in the majority of sexually
      reproducing diploids. The abundance of recessive deleterious mutations in natural
      populations suggests they are likely to be present on a chromosome when a new
      adaptive mutation occurs, yet the dynamics of recessive deleterious hitchhikers
      and their impact on adaptation remains poorly understood. Here we model how a
      recessive deleterious mutation impacts the fate of a genetically linked dominant
      beneficial mutation. The frequency trajectory of the adaptive mutation in this
      case is dramatically altered and results in what we have termed a "staggered
      sweep." It is named for its three-phased trajectory: (i) Initially, the two
      linked mutations have a selective advantage while rare and will increase in
      frequency together, then (ii), at higher frequencies, the recessive hitchhiker is
      exposed to selection and can cause a balanced state via heterozygote advantage
      (the staggered phase), and (iii) finally, if recombination unlinks the two
      mutations, then the beneficial mutation can complete the sweep to fixation. Using
      both analytics and simulations, we show that strongly deleterious recessive
      mutations can substantially decrease the probability of fixation for nearby
      beneficial mutations, thus creating zones in the genome where adaptation is
      suppressed. These mutations can also significantly prolong the number of
      generations a beneficial mutation takes to sweep to fixation, and cause the
      genomic signature of selection to resemble that of soft or partial sweeps. We
      show that recessive deleterious variation could impact adaptation in humans and
      Drosophila. 

PMID- 25941394
TI  - Signature properties of water: Their molecular electronic origins.
AB  - Water challenges our fundamental understanding of emergent materials properties
      from a molecular perspective. It exhibits a uniquely rich phenomenology including
      dramatic variations in behavior over the wide temperature range of the liquid
      into water's crystalline phases and amorphous states. We show that many-body
      responses arising from water's electronic structure are essential mechanisms
      harnessed by the molecule to encode for the distinguishing features of its
      condensed states. We treat the complete set of these many-body responses
      nonperturbatively within a coarse-grained electronic structure derived
      exclusively from single-molecule properties. Such a "strong coupling" approach
      generates interaction terms of all symmetries to all orders, thereby enabling
      unique transferability to diverse local environments such as those encountered
      along the coexistence curve. The symmetries of local motifs that can potentially
      emerge are not known a priori. Consequently, electronic responses unfiltered by
      artificial truncation are then required to embody the terms that tip the balance
      to the correct set of structures. Therefore, our fully responsive molecular model
      produces, a simple, accurate, and intuitive picture of water's complexity and its
      molecular origin, predicting water's signature physical properties from ice,
      through liquid-vapor coexistence, to the critical point. 

PMID- 25941397
TI  - Retraction for Messer et al., Dengue virus envelope protein domain I/II hinge
      determines long-lived serotype-specific dengue immunity.

PMID- 25941395
TI  - Bats adjust their mouth gape to zoom their biosonar field of view.
AB  - Active sensing, where sensory acquisition is actively modulated, is an inherent
      component of almost all sensory systems. Echolocating bats are a prime example of
      active sensing. They can rapidly adjust many of their biosonar parameters to
      optimize sensory acquisition. They dynamically adjust pulse design, pulse
      duration, and pulse rate within dozens of milliseconds according to the sensory
      information that is required for the task that they are performing. The least
      studied and least understood degree of freedom in echolocation is emission
      beamforming--the ability to change the shape of the sonar sound beam in a
      functional way. Such an ability could have a great impact on the bat's control
      over its sensory perception. On the one hand, the bat could direct more energy
      into a narrow sector to zoom its biosonar field of view, and on the other hand,
      it could widen the beam to increase the space that it senses. We show that freely
      behaving bats constantly control their biosonar field of view in natural
      situations by rapidly adjusting their emitter aperture--the mouth gape. The bats
      dramatically narrowed the beam when entering a confined space, and they
      dramatically widened it within dozens of milliseconds when flying toward open
      space. Hence, mouth-emitting bats dynamically adjust their mouth gape to optimize
      the area that they sense with their echolocation system.

PMID- 25941396
TI  - Mechanism of pyranopterin ring formation in molybdenum cofactor biosynthesis.
AB  - The molybdenum cofactor (Moco) is essential for all kingdoms of life, plays
      central roles in various biological processes, and must be biosynthesized de
      novo. During Moco biosynthesis, the characteristic pyranopterin ring is
      constructed by a complex rearrangement of guanosine 5'-triphosphate (GTP) into
      cyclic pyranopterin (cPMP) through the action of two enzymes, MoaA and MoaC
      (molybdenum cofactor biosynthesis protein A and C, respectively). Conventionally,
      MoaA was considered to catalyze the majority of this transformation, with MoaC
      playing little or no role in the pyranopterin formation. Recently, this view was
      challenged by the isolation of 3',8-cyclo-7,8-dihydro-guanosine 5'-triphosphate
      (3',8-cH2GTP) as the product of in vitro MoaA reactions. To elucidate the
      mechanism of formation of Moco pyranopterin backbone, we performed biochemical
      characterization of 3',8-cH2GTP and functional and X-ray crystallographic
      characterizations of MoaC. These studies revealed that 3',8-cH2GTP is the only
      product of MoaA that can be converted to cPMP by MoaC. Our structural studies
      captured the specific binding of 3',8-cH2GTP in the active site of MoaC. These
      observations provided strong evidence that the physiological function of MoaA is
      the conversion of GTP to 3',8-cH2GTP (GTP 3',8-cyclase), and that of MoaC is to
      catalyze the rearrangement of 3',8-cH2GTP into cPMP (cPMP synthase). Furthermore,
      our structure-guided studies suggest that MoaC catalysis involves the dynamic
      motions of enzyme active-site loops as a way to control the timing of interaction
      between the reaction intermediates and catalytically essential amino acid
      residues. Thus, these results reveal the previously unidentified mechanism behind
      Moco biosynthesis and provide mechanistic and structural insights into how
      enzymes catalyze complex rearrangement reactions. 

PMID- 25941398
TI  - Symbolic bones and interethnic violence in a frontier zone, northwest Mexico, ca.
      500-900 C.E.
AB  - Although extensive deposits of disarticulated, commingled human bones are common
      in the prehispanic Northern Frontier of Mesoamerica, detailed bioarchaeological
      analyses of them are not. To our knowledge, this article provides the first such
      analysis of bone from a full residential-ceremonial complex and evaluates
      multiple hypotheses about its significance, concluding that the bones actively
      represented interethnic violence as well as other relationships among persons
      living and dead. Description of these practices is important to the discussion of
      multiethnic societies because the frontier was a context where urbanism and
      complexity were emerging and groups with the potential to form multiethnic
      societies were interacting, possibly in the same ways that groups did before the
      formation of larger multiethnic city-states in the core of Mesoamerica. 

PMID- 25941399
TI  - Oncogenic and RASopathy-associated K-RAS mutations relieve membrane-dependent
      occlusion of the effector-binding site.
AB  - K-RAS4B (Kirsten rat sarcoma viral oncogene homolog 4B) is a prenylated, membrane
      associated GTPase protein that is a critical switch for the propagation of growth
      factor signaling pathways to diverse effector proteins, including rapidly
      accelerated fibrosarcoma (RAF) kinases and RAS-related protein guanine nucleotide
      dissociation stimulator (RALGDS) proteins. Gain-of-function KRAS mutations occur
      frequently in human cancers and predict poor clinical outcome, whereas germ-line
      mutations are associated with developmental syndromes. However, it is not known
      how these mutations affect K-RAS association with biological membranes or whether
      this impacts signal transduction. Here, we used solution NMR studies of K-RAS4B
      tethered to nanodiscs to investigate lipid bilayer-anchored K-RAS4B and its
      interactions with effector protein RAS-binding domains (RBDs). Unexpectedly, we
      found that the effector-binding region of activated K-RAS4B is occluded by
      interaction with the membrane in one of the NMR-observable, and thus highly
      populated, conformational states. Binding of the RAF isoform ARAF and RALGDS RBDs
      induced marked reorientation of K-RAS4B from the occluded state to RBD-specific
      effector-bound states. Importantly, we found that two Noonan syndrome-associated
      mutations, K5N and D153V, which do not affect the GTPase cycle, relieve the
      occluded orientation by directly altering the electrostatics of two membrane
      interaction surfaces. Similarly, the most frequent KRAS oncogenic mutation G12D
      also drives K-RAS4B toward an exposed configuration. Further, the D153V and G12D
      mutations increase the rate of association of ARAF-RBD with lipid bilayer
      tethered K-RAS4B. We revealed a mechanism of K-RAS4B autoinhibition by membrane
      sequestration of its effector-binding site, which can be disrupted by disease
      associated mutations. Stabilizing the autoinhibitory interactions between K-RAS4B
      and the membrane could be an attractive target for anticancer drug discovery. 

PMID- 25941400
TI  - Evaluating a groundwater supply contamination incident attributed to Marcellus
      Shale gas development.
AB  - High-volume hydraulic fracturing (HVHF) has revolutionized the oil and gas
      industry worldwide but has been accompanied by highly controversial incidents of
      reported water contamination. For example, groundwater contamination by stray
      natural gas and spillage of brine and other gas drilling-related fluids is known
      to occur. However, contamination of shallow potable aquifers by HVHF at depth has
      never been fully documented. We investigated a case where Marcellus Shale gas
      wells in Pennsylvania caused inundation of natural gas and foam in initially
      potable groundwater used by several households. With comprehensive 2D gas
      chromatography coupled to time-of-flight mass spectrometry (GCxGC-TOFMS), an
      unresolved complex mixture of organic compounds was identified in the aquifer.
      Similar signatures were also observed in flowback from Marcellus Shale gas wells.
      A compound identified in flowback, 2-n-Butoxyethanol, was also positively
      identified in one of the foaming drinking water wells at nanogram-per-liter
      concentrations. The most likely explanation of the incident is that stray natural
      gas and drilling or HF compounds were driven ~ 1-3 km along shallow to
      intermediate depth fractures to the aquifer used as a potable water source. Part
      of the problem may have been wastewaters from a pit leak reported at the nearest
      gas well pad-the only nearby pad where wells were hydraulically fractured before
      the contamination incident. If samples of drilling, pit, and HVHF fluids had been
      available, GCxGC-TOFMS might have fingerprinted the contamination source. Such
      evaluations would contribute significantly to better management practices as the
      shale gas industry expands worldwide.

PMID- 25941401
TI  - Organization and dynamics of the nonhomologous end-joining machinery during DNA
      double-strand break repair.
AB  - Nonhomologous end-joining (NHEJ) is a major repair pathway for DNA double-strand
      breaks (DSBs), involving synapsis and ligation of the broken strands. We describe
      the use of in vivo and in vitro single-molecule methods to define the
      organization and interaction of NHEJ repair proteins at DSB ends. Super
      resolution fluorescence microscopy allowed the precise visualization of XRCC4,
      XLF, and DNA ligase IV filaments adjacent to DSBs, which bridge the broken
      chromosome and direct rejoining. We show, by single-molecule FRET analysis of the
      Ku/XRCC4/XLF/DNA ligase IV NHEJ ligation complex, that end-to-end synapsis
      involves a dynamic positioning of the two ends relative to one another. Our
      observations form the basis of a new model for NHEJ that describes the mechanism
      whereby filament-forming proteins bridge DNA DSBs in vivo. In this scheme, the
      filaments at either end of the DSB interact dynamically to achieve optimal
      configuration and end-to-end positioning and ligation. 

PMID- 25941402
TI  - Drosophila Ncd reveals an evolutionarily conserved powerstroke mechanism for
      homodimeric and heterodimeric kinesin-14s.
AB  - Drosophila melanogaster kinesin-14 Ncd cross-links parallel microtubules at the
      spindle poles and antiparallel microtubules within the spindle midzone to play
      roles in bipolar spindle assembly and proper chromosome distribution. As observed
      for Saccharomyces cerevisiae kinesin-14 Kar3Vik1 and Kar3Cik1, Ncd binds adjacent
      microtubule protofilaments in a novel microtubule binding configuration and uses
      an ATP-promoted powerstroke mechanism. The hypothesis tested here is that
      Kar3Vik1 and Kar3Cik1, as well as Ncd, use a common ATPase mechanism for force
      generation even though the microtubule interactions for both Ncd heads are
      modulated by nucleotide state. The presteady-state kinetics and computational
      modeling establish an ATPase mechanism for a powerstroke model of Ncd that is
      very similar to those determined for Kar3Vik1 and Kar3Cik1, although these
      heterodimers have one Kar3 catalytic motor domain and a Vik1/Cik1 partner motor
      homology domain whose interactions with microtubules are not modulated by
      nucleotide state but by strain. The results indicate that both Ncd motor heads
      bind the microtubule lattice; two ATP binding and hydrolysis events are required
      for each powerstroke; and a slow step occurs after microtubule collision and
      before the ATP-promoted powerstroke. Note that unlike conventional myosin-II or
      other processive molecular motors, Ncd requires two ATP turnovers rather than one
      for a single powerstroke-driven displacement or step. These results are
      significant because all metazoan kinesin-14s are homodimers, and the results
      presented show that despite their structural and functional differences, the
      heterodimeric and homodimeric kinesin-14s share a common evolutionary structural
      and mechanochemical mechanism for force generation. 

PMID- 25941404
TI  - Correction for Makris et al., Developing functional musculoskeletal tissues
      through hypoxia and lysyl oxidase-induced collagen cross-linking.

PMID- 25941403
TI  - Malaria continues to select for sickle cell trait in Central Africa.
AB  - Sickle cell disease (SCD) is a genetic disorder that poses a serious health
      threat in tropical Africa, which the World Health Organization has declared a
      public health priority. Its persistence in human populations has been attributed
      to the resistance it provides to Plasmodium falciparum malaria in its
      heterozygous state, called sickle cell trait (SCT). Because of migration, SCT is
      becoming common outside tropical countries: It is now the most important genetic
      disorder in France, affecting one birth for every 2,400, and one of the most
      common in the United States. We assess the strength of the association between
      SCT and malaria, using current data for both SCT and malaria infections. A total
      of 3,959 blood samples from 195 villages distributed over the entire Republic of
      Gabon were analyzed. Hemoglobin variants were identified by using HPLCy (HPLC).
      Infections by three species of Plasmodium were detected by PCR followed by
      sequencing of a 201-bp fragment of cytochrome b. An increase of 10% in P.
      falciparum malaria prevalence is associated with an increase by 4.3% of SCT
      carriers. An increase of 10 y of age is associated with an increase by 5.5% of
      SCT carriers. Sex is not associated with SCT. These strong associations show that
      malaria remains a selective factor in current human populations, despite the
      progress of medicine and the actions undertaken to fight this disease. Our
      results provide evidence that evolution is still present in humans, although this
      is sometimes questioned by scientific, political, or religious personalities. 

PMID- 25941405
TI  - Cytoplasmic dynein regulates its attachment to microtubules via nucleotide state
      switched mechanosensing at multiple AAA domains.
AB  - Cytoplasmic dynein is a homodimeric microtubule (MT) motor protein responsible
      for most MT minus-end-directed motility. Dynein contains four AAA+ ATPases (AAA:
      ATPase associated with various cellular activities) per motor domain (AAA1-4).
      The main site of ATP hydrolysis, AAA1, is the only site considered by most dynein
      motility models. However, it remains unclear how ATPase activity and MT binding
      are coordinated within and between dynein's motor domains. Using optical
      tweezers, we characterize the MT-binding strength of recombinant dynein monomers
      as a function of mechanical tension and nucleotide state. Dynein responds
      anisotropically to tension, binding tighter to MTs when pulled toward the MT plus
      end. We provide evidence that this behavior results from an asymmetrical bond
      that acts as a slip bond under forward tension and a slip-ideal bond under
      backward tension. ATP weakens MT binding and reduces bond strength anisotropy,
      and unexpectedly, so does ADP. Using nucleotide binding and hydrolysis mutants,
      we show that, although ATP exerts its effects via binding AAA1, ADP effects are
      mediated by AAA3. Finally, we demonstrate "gating" of AAA1 function by AAA3. When
      tension is absent or applied via dynein's C terminus, ATP binding to AAA1 induces
      MT release only if AAA3 is in the posthydrolysis state. However, when tension is
      applied to the linker, ATP binding to AAA3 is sufficient to "open" the gate.
      These results elucidate the mechanisms of dynein-MT interactions, identify
      regulatory roles for AAA3, and help define the interplay between mechanical
      tension and nucleotide state in regulating dynein motility. 

PMID- 25941406
TI  - Apolipoprotein CIII links islet insulin resistance to beta-cell failure in
      diabetes.
AB  - Insulin resistance and beta-cell failure are the major defects in type 2 diabetes
      mellitus. However, the molecular mechanisms linking these two defects remain
      unknown. Elevated levels of apolipoprotein CIII (apoCIII) are associated not only
      with insulin resistance but also with cardiovascular disorders and inflammation.
      We now demonstrate that local apoCIII production is connected to pancreatic islet
      insulin resistance and beta-cell failure. An increase in islet apoCIII causes
      promotion of a local inflammatory milieu, increased mitochondrial metabolism,
      deranged regulation of beta-cell cytoplasmic free Ca(2+) concentration
      ([Ca(2+)]i) and apoptosis. Decreasing apoCIII in vivo results in improved glucose
      tolerance, and pancreatic apoCIII knockout islets transplanted into diabetic
      mice, with high systemic levels of the apolipoprotein, demonstrate a normal
      [Ca(2+)]i response pattern and no hallmarks of inflammation. Hence, under
      conditions of islet insulin resistance, locally produced apoCIII is an important
      diabetogenic factor involved in impairment of beta-cell function and may thus
      constitute a novel target for the treatment of type 2 diabetes mellitus. 

PMID- 25941407
TI  - The membrane remodeling protein Pex11p activates the GTPase Dnm1p during
      peroxisomal fission.
AB  - The initial phase of peroxisomal fission requires the peroxisomal membrane
      protein Peroxin 11 (Pex11p), which remodels the membrane, resulting in organelle
      elongation. Here, we identify an additional function for Pex11p, demonstrating
      that Pex11p also plays a crucial role in the final step of peroxisomal fission:
      dynamin-like protein (DLP)-mediated membrane scission. First, we demonstrate that
      yeast Pex11p is necessary for the function of the GTPase Dynamin-related 1
      (Dnm1p) in vivo. In addition, our data indicate that Pex11p physically interacts
      with Dnm1p and that inhibiting this interaction compromises peroxisomal fission.
      Finally, we demonstrate that Pex11p functions as a GTPase activating protein
      (GAP) for Dnm1p in vitro. Similar observations were made for mammalian Pex11beta
      and the corresponding DLP Drp1, indicating that DLP activation by Pex11p is
      conserved. Our work identifies a previously unknown requirement for a GAP in DLP
      function. 

PMID- 25941409
TI  - Reply to Li et al.: Insufficient evidence for the contribution of regional
      transport to severe haze formation in Beijing.

PMID- 25941408
TI  - Activation of the bacterial thermosensor DesK involves a serine zipper
      dimerization motif that is modulated by bilayer thickness.
AB  - DesK is a bacterial thermosensor protein involved in maintaining membrane
      fluidity in response to changes in environmental temperature. Most likely, the
      protein is activated by changes in membrane thickness, but the molecular
      mechanism of sensing and signaling is still poorly understood. Here we aimed to
      elucidate the mode of action of DesK by studying the so-called "minimal sensor
      DesK" (MS-DesK), in which sensing and signaling are captured in a single
      transmembrane segment. This simplified version of the sensor allows investigation
      of membrane thickness-dependent protein-lipid interactions simply by using
      synthetic peptides, corresponding to the membrane-spanning parts of functional
      and nonfunctional mutants of MS-DesK incorporated in lipid bilayers with varying
      thicknesses. The lipid-dependent behavior of the peptides was investigated by
      circular dichroism, tryptophan fluorescence, and molecular modeling. These
      experiments were complemented with in vivo functional studies on MS-DesK mutants.
      Based on the results, we constructed a model that suggests a new mechanism for
      sensing in which the protein is present as a dimer and responds to an increase in
      bilayer thickness by membrane incorporation of a C-terminal hydrophilic motif.
      This results in exposure of three serines on the same side of the transmembrane
      helices of MS-DesK, triggering a switching of the dimerization interface to allow
      the formation of a serine zipper. The final result is activation of the kinase
      state of MS-DesK. 

PMID- 25941410
TI  - Reinstate regional transport of PM2.5 as a major cause of severe haze in Beijing.

PMID- 25941411
TI  - Reply to Ashktorab et al.: Mutational landscape of colon cancers in African
      Americans.

PMID- 25941412
TI  - Next-generation sequencing in African Americans with colorectal cancer.

PMID- 25941413
TI  - Reply to Gerlee and Altrock: Diffusion and population size in game theory models
      of cancer.

PMID- 25941414
TI  - Complexity and stability in growing cancer cell populations.

PMID- 25941415
TI  - Interpreting the neurodevelopmental hypothesis of schizophrenia in the context of
      normal brain development and ageing.

PMID- 25941416
TI  - Pyruvate dehydrogenase, Randle cycle, and skeletal muscle insulin resistance.

PMID- 25941417
TI  - A multisource feedback tool to assess ward round leadership skills of senior
      paediatric trainees: (2) Testing reliability and practicability.
AB  - BACKGROUND: A five-domain multisource feedback (MSF) tool was previously
      developed in 2009-2010 by the authors to assess senior paediatric trainees' ward
      round leadership skills. OBJECTIVES: To determine whether this MSF tool is
      practicable and reliable, whether individuals' feedback varies over time and
      trainees' views of the tool. METHODS: The MSF tool was piloted (April-July 2011)
      and field tested (September 2011-February 2013) with senior paediatric trainees.
      A focus group held at the end of field testing obtained trainees' views of the
      tool. RESULTS: In field testing, 96/115 (84%) trainees returned 633 individual
      assessments from three different ward rounds over 18 months. The MSF tool had
      high reliability (Cronbach's alpha 0.84, G coefficient 0.8 for three raters). In
      all five domains, data were shifted to the right with scores of 3 (good) and 4
      (excellent). Consultants gave significantly lower scores (p<0.001), as did
      trainees for self-assessment (p<0.001). There was no significant change in MSF
      scores over 18 months but comments showed that trainees' performance improved.
      Trainees valued these comments and the MSF tool but had concerns about time taken
      for feedback and confusion about tool use and the paediatric assessment strategy.
      CONCLUSIONS: A five-domain MSF tool was found to be reliable on pilot and field
      testing, practicable to use and liked by trainees. Comments on performance were
      more helpful than scores in giving trainees feedback.

PMID- 25941418
TI  - A multisource feedback tool to assess ward round leadership skills of senior
      paediatric trainees: (1) Development of tool.
AB  - BACKGROUND: Leading a ward round is an essential skill for hospital consultants
      and senior trainees but is rarely assessed during training. OBJECTIVES: To
      investigate the key attributes for ward round leadership and to use these results
      to develop a multisource feedback (MSF) tool to assess the ward round leadership
      skills of senior specialist trainees. METHODS: A panel of experts comprising four
      senior paediatric consultants and two nurse managers were interviewed from May to
      August 2009. From analysis of the interview transcripts, 10 key themes emerged. A
      structured questionnaire based on the key themes was designed and sent
      electronically to paediatric consultants, nurses and trainees at a large
      university hospital (June-October 2010). RESULTS: 81 consultants, nurses and
      trainees responded to the survey. The internal consistency of this tool was high
      (Cronbach's alpha 0.95). Factor analysis showed that five factors accounted for
      72% of variance. The five key areas for ward round leadership were communication
      skills, preparation and organisation, teaching and enthusiasm, team working and
      punctuality; communication was the most important key theme. A MSF tool for ward
      round leadership skills was developed with these areas as five domains.
      CONCLUSIONS: We believe that this tool will add to the current assessment tools
      available by providing feedback about ward round leadership skills.

PMID- 25941419
TI  - Laser Therapy Best and Good Paper Awards: The Results are in!

PMID- 25941420
TI  - History of the World Federation of Societies for Laser Medicine and Surgery
      (WFSLMS) and its Non-Profit Organization (NPO-WFSLMS): Part 2: 2(nd) WFSLMS
      Meeting (2009) to the present.
AB  - BACKGROUND: The first part of this historical overview, (see Laser Therapy, 2014;
      23: 89-95), took the reader from the conception of the WFSLMS to its inception at
      the inaugural meeting in Tokyo, 2005 and events up to the 2009 2(nd) WFSLMS in
      Tokyo when the author was the congress president. The previous article also dealt
      with the necessity for founding a non-profit organization, NPO-WFSLMS, to handle
      the commercial and social responsibilities of the WFSLMS. For details, please
      refer to that previous article. Meetings: The 2(nd) WFSLMS congress was
      successfully held in 2009 in Japan, under the presidency of Professor Krishna
      Rau. The third WFSLMS meeting was planned for Paris in 2013 together with the
      20(th) ISLSM congress under the Meeting Presidency of Dr Jean Abitbol, while the
      19(th) ISLSM was to be held in Korea in 2011 under the Meeting Presidency of
      Prof. Jin-Wang Kim. Unforseen problems beyond the control of the organizers
      forced the cancellation of both the 19(th) and 20(th) meetings of the ISLSM, the
      latter also being the location of the planned third WFSLMS congress in Paris, but
      with the cooperation of the organizers of the 5(th) congress of the International
      Phototherapy Association (IPTA) the 3(rd) WFSLMS meeting was held in Lithuania,
      again under the presidency of Prof Rau concurrently with the 20(th) ISLSM, at
      which much was debated regarding the future course of NPO-WFSLMS and WFSLMS. The
      venue of the 2015 21(st) ISLSM Congress was set as Indore, India, and the 4(th)
      WFSLMS meeting was allocated to Florence, Italy, in tandem with the 22(nd) ISLSM
      congress. PROJECTS: In the interim, NPO-WFSLMS effectively managed laser
      education programs in Japan for developing country doctors, and also handled the
      donation of laser systems to Vietnam and Thailand, the latter being under the
      auspices of the Greek Medical Laser Association, together with associated
      education programs. The laser-based Blood Saving Campaign (BSaC) has been
      actively promoted in Asian countries up to the present, designed to minimize the
      need for transfusions and prevent intraoperative blood loss through the
      hemostatic properties of surgical lasers, bloodless minimally-invasive treatment
      with photodynamic therapy (PDT) and noninvasive LLLT. THE FUTURE: The WFSLMS will
      make more active overtures to solidify the inter-society cooperation among as
      many of the major laser societies as possible, both national and international.
      There are problems to be faced and overcome, but in a mood of cautious optimism,
      NPO-WFSLMS will work with WFSLMS and ISLSM towards this very worthwhile goal.

PMID- 25941421
TI  - The use of Intravenous Laser Blood Irradiation (ILBI) at 630-640 nm to prevent
      vascular diseases and to increase life expectancy.
AB  - BACKGROUND AND AIMS: The mortality rate from vascular diseases is one of the
      highest. The use of Intravenous Laser Blood Irradiation (ILBI) within the last 30
      years has demonstrated high efficacy in the treatment of vascular, cardiac and
      other systemic diseases. RATIONALE: Laser energy at 630-640 nanometers is
      arguably the most effective for irradiation of blood and the vascular wall.
      Photons at this wavelength are absorbed by oxygen, improve microcirculation, can
      change the viscosity of the blood and affect vascular endothelium. CONCLUSIONS:
      In summary, more than 25 years of experience of using laser energy at 630-640 nm
      has shown that this waveband directly influences the parameters of all cells in
      the blood, blood plasma, the coagulation process and all the structural
      components of the vascular wall. Additionally, ILBI directly or indirectly
      affects the cells of the immune system, hormones, and exchange processes in an
      organism, thereby not only improving the function of the vascular system, but
      also the other systems of an organism. It can finally lead to lower the incidence
      and number of vascular diseases, and indirectly to the reduction of the number of
      diseases in other organs and even systemically, thus helping to prolong the
      lifespan.

PMID- 25941422
TI  - Preliminary results of highly localized plantar irradiation with low incident
      levels of mid-infrared energy which contributes to the prevention of dementia
      associated with underlying diabetes mellitus.
AB  - BACKGROUND AND AIMS: The incidence of vascular dementia (VD) and Alzheimer's
      disease (AD) has recently increased and the prevention of progression of these
      diseases is very difficult. RESULTS: The application of pinpoint plantar long
      wavelength infrared light irradiation (PP-LILI) to a patient's sole, at the point
      where the line drawn between the first and second metatarsal heads intersects
      with the vertical line from the medial malleolus, was effective in increasing
      blood flow to the facial artery, elevating high-density lipoprotein cholesterol
      (HDL-C) levels, and reducing insulin resistance. CONCLUSIONS: We found that these
      effects of PP-LILI might be helpful for preventing VD and AD, conditions that are
      becoming a social problem in an aging Japanese society.

PMID- 25941423
TI  - A comparison of Er, Cr: YSGG laser with ultrasonic preparation on the seal of
      retrograde cavities.
AB  - BACKGROUND AND AIM: The aim of this in vitro study was to compare Er, Cr: YSGG
      laser with ultrasonic preparation on the seal of retrograde cavities. MATERIALS
      AND METHODS: Twenty-eight maxillary anterior teeth were used in this study. After
      removing the crowns, the canals were prepared with the step-back technique and
      filled with guttapercha. Three millimeters below the apex; each root was cut with
      a fissure diamond bur. The root surfaces were then covered with nail polish and
      three millimeters deep retrograde class I cavities were prepared, using Er, Cr:
      YSGG laser (group L=12 roots) or ultrasonic retro-tip (group U=12 roots). Four
      roots were arranged for negative and positive control groups. Retrograde cavities
      were then filled with mineral trioxide aggregate (MTA) and teeth were placed in
      2% methylene blue dye for 72 hours. The amount of dye penetration in sagittal
      sections of each tooth was measured with a stereomicroscope. An independent
      sample t-test was used for statistical analysis. RESULTS: Cavities prepared with
      the Er, Cr: YSGG laser (1.61 + 0.81) showed significantly less micro-leakage than
      those prepared with the ultrasound (2.55+ 1.84) (P value =0.02). CONCLUSIONS:
      Under the conditions of this research, the use of Er, Cr: YSGG laser for
      retrograde cavity preparation causes significantly less apical leakage and may
      increase the success rate of endodontic surgeries.

PMID- 25941424
TI  - Efficacy of LLLT in swelling and pain control after the extraction of lower
      impacted third molars.
AB  - INTRODUCTION AND AIM: Low Level Laser Therapy (LLLT) can facilitate wound healing
      stimulating a more rapid resolution and an earlier start for the proliferation
      phase. The purpose of this study is to evaluate the effects of LLLT on
      postoperative pain and oedema following the removal of impacted lower third
      molars. MATERIALS AND METHODS: Fifty-nine patients, who were to undergo surgical
      removal of their lower third molars, were studied. Patients were randomly
      allocated to one of three groups: 17 patients LLLT + traditional drug treatment17
      patients traditional drug treatment as control group25 patients treated with LLLT
      only on one side+traditional drug treatment. The laser we have used for this
      study is a diode laser, GaAs, which delivers both in the infrared band at the
      wavelength of 910 nanometers (pulsed and superpulsed source), and in the visible
      (continuous source) at the wavelength of 650 nanometers (red). LLLT was performed
      just after the intervention and approximately 12 hours after surgery delivering
      240 J in 15 minutes with theoretical fluence values of 480 J/cm(2) and 31 J/cm(2)
      for every minute of irradiation. We considered and signed with a label constant
      landmarks on both sides of the face of each patient; measurements were taken:
      before the surgery, after the surgery right after the 1st laser treatment, after
      approximately 24 hours after the 2(nd) laser treatment. RESULTS: We collected all
      the values of the oedema measurements and the VAS reports and performed a
      statistical analysis by means One-way Analysis of Variance (ANOVA) test: for the
      evaluated values (X, Y, Z) an extremely significant difference was found with p
      values of 0.003 for Y at the first evaluation (pre-12 hours) and less than 0.001
      for the other evaluations. A significant result was obtained for VAS recorded at
      hospital discharge (p<0.0001). CONCLUSIONS: This study demonstrates that LLLT is
      effective on postoperative pain and oedema accelerating healing time and reducing
      patients distress.

PMID- 25941425
TI  - The "at-home LLLT" in temporo-mandibular disorders pain control: a pilot study.
AB  - OBJECTIVES: The Temporo-Mandibular Disorders (TMD) are a set of dysfunctional
      patterns concerning the temporo-mandibular joints (TMJ) and the masticatory
      muscles; its main symptom is pain, probably caused by inflammatory changes in the
      synovial membrane, alterations in the bone marrow of the mandibular condyle and
      impingement and compression. The aim of this preliminary study was to investigate
      the effectiveness in the TMD pain reduction of a new laser device recently
      proposed by the commerce that, due to its reduced dimensions and to be a class I
      laser according the ANSI classification, may be used at home by the patient
      himself. MATERIAL AND METHODS: Twenty-four patients with TMD were randomly
      selected: the inclusion criteria for the sample was the diagnosis of mono- or bi
      lateral TMD, with acute pain restricted to the joint area, associated with the
      absence of any muscle tenderness during palpation. The patients were randomly
      assigned to two groups: Group 1 (12 patients): patients receiving real LLLT
      (experimental group). Group 2 (12 patients): patients receiving inactive laser
      (placebo group). The treatment was performed once a day for two weeks with an 808
      nm diode laser by the patient himself with irradiation of the cutaneous zone
      corresponding to the TMJ for 15 minutes each side. Each patient was instructed to
      express its pain in a visual analogue scale (VAS) making a perpendicular line
      between the two extremes representing the felt pain level. Statistical analysis
      was realized with GraphPad Instat Software, where P<0.05 was considered
      significant and P<0.01 very significant. RESULTS: The patient's pain evaluation
      was expressed in the two study groups before the treatment, 1 week and two weeks
      after the treatment. The differences between the two groups result extremely
      significant with p<0.0001 for the comparison of VAS value after 1 and 2 weeks.
      CONCLUSION: This study, even if it may be considered such a pilot study,
      investigated a new way to control the pain in the temporo-mandibular diseases by
      an at home self administered laser device. RESULTS are encouraging but they will
      have to be confirmed by greater studies.

PMID- 25941427
TI  - The Fifth Year of JCEH: The Year of Recognition.

PMID- 25941426
TI  - Yellow laser acupuncture - A new option for prevention and early intervention of
      lifestyle-related diseases: A randomized, placebo-controlled trial in volunteers.
AB  - BACKGROUND AND AIMS: The yellow laser constitutes a totally new option in the
      field of laser acupuncture, in addition to the already existing red, near
      infrared, green and violet lasers. Especially for so called lifestyle-related
      diseases, this could open up new methods of integrative therapy. The goal of the
      present study was to investigate among other parameters blood pressure (BP),
      heart rate (HR), heart rate variability (HRV), and temperature effects before,
      during, and after stimulation of different acupoints with yellow laser. SUBJECTS
      AND METHODS: We recruited 26 healthy volunteers (13 female, 13 male; mean age +/-
      SD 24.1 +/- 3.3 years) at the Medical University of Graz. The acupoints Baihui,
      Neiguan, Taichong and a placebo point were stimulated with a 589 nm (50 mW, 500
      um; 5 min) yellow laser. Blood pressure was measured noninvasively at the wrist;
      for the registration of the electrocardiogram a medilog AR12 HRV system was used.
      Effects on temperature were measured with a Flir i7 infrared camera. RESULTS:
      There were significant decreases after yellow laser acupuncture in the systolic
      BP, diastolic BP also decreased (n.s.). HRV in both (men and women) increased.
      The temperature during the yellow laser stimulation decreased significantly in
      all measured points. After the stimulation it increased again significantly.
      Based on a questionnaire volunteers reported a significantly decreased level of
      stress after yellow laser stimulation. CONCLUSION: Significant positive effects
      on BP and well-being were found after yellow laser stimulation. The results are
      very promising and can be very important especially for the treatment of
      lifestyle related diseases.

PMID- 25941428
TI  - Optimal Duration of Pegylated Interferon Plus Ribavirin Therapy for Chronic
      Hepatitis C Genotype 3 Patients who do not Achieve Rapid Virological Response.
AB  - BACKGROUND/OBJECTIVES: Chronic hepatitis C (CHC) genotype-3 (G-3) patients
      treated with standard 24-week pegylated interferon plus ribavirin(PEG-RBV)
      therapy achieve sustained virological response(SVR) rate of 69-82%. Patients who
      do not achieve rapid virological response(RVR) have lower SVR rate. Data
      regarding optimal management of this subgroup is scarce. We aimed to determine
      the most appropriate treatment duration in CHC G-3 patients who do not achieve
      RVR. METHODS: Treatment naive CHC G-3 patients treated with PEG-RBV therapy were
      included in this retrospective analysis. Patients with cirrhosis were excluded.
      RVR was assessed in all patients beyond the year 2007. RVR non-achievers were
      advised extended treatment beyond 24 weeks. RESULTS: Of the total 685 patients
      started on treatment, 646 completed treatment (mean age 39.1 +/- 12 years, 68.3%
      males). In the pre-'RVR assessment' period (2004-2006), SVR with standard 24 week
      therapy was 72.3% (112/155). In post-'RVR assessment' period (2007-2013), 75.8%
      (402/530) patients achieved RVR; and 91.5% (368/402) of these achieved SVR with
      standard 24 weeks therapy. Among RVR non-achievers (n = 128), 51 patients opted
      for extended 36 week therapy, 12 for 48 week therapy, while 65 stopped therapy at
      24 weeks. Choice of treatment duration was dependent entirely on the
      affordability of the patient. SVR with extended therapy (36/48 weeks) was
      significantly higher than standard 24 week therapy in RVR non-achievers (82.5%
      vs. 52.3%; P = 0.003). However, SVR rate in 36 week group was not significantly
      different from 48 week group (84.3% vs. 75%; P = 0.425]. On multivariate
      analysis, duration of treatment (36/48 week vs. 24 week; P < 0.001) was
      significantly associated with SVR. CONCLUSIONS: SVR rates in CHC G-3 patients
      treated with PEG-RBV in northern India were comparable to western data. Standard
      24 week therapy is adequate for RVR-achievers. However, in RVR non-achievers,
      extended 36 week therapy significantly improves SVR, while further extension to
      48 week does not provide any additional advantage.

PMID- 25941429
TI  - Clinical and biochemical profile of tuberculosis in patients with liver
      cirrhosis.
AB  - INTRODUCTION: There is paucity of data on tuberculosis and antituberculous
      therapy (ATT) induced hepatotoxicity in patients with chronic liver disease. AIM:
      To study demographic, clinical characteristics of tuberculosis, pattern of drug
      induced liver injury and treatment responses to ATT in patients with liver
      cirrhosis. MATERIAL AND METHOD: All cases of liver cirrhosis diagnosed with
      tuberculosis (TB) between January 2010 and June 2013 were enrolled. Drug induced
      liver injury (DILI) was defined as follows (1) an aspartate aminotransferase
      (AST)/alanine aminotransferase (ALT) value exceeding 3 times the normal upper
      limit if the baseline level was normal (<40 IU/L), or an AST/ALT exceeding 2
      times the baseline level if the baseline level was abnormal and an absolute
      increase in serum bilirubin >2 mg/dl from baseline. RESULTS: Sixty seven patients
      had confirmed TB with underlying cirrhosis and formed the study group. The mean
      age was 52 +/- 12 years and M:F ratio was 57:10. Mean Child Turcotte Pugh (CTP)
      score 8.5 +/- 1.5 (CTP A:B:C:7:44:16). The sites of TB included: pulmonary (25,
      37%); pleural effusion (10, 16%) peritoneal (19, 29%); chest lymph nodes (3, 4%);
      liver (1, 1.5%); intestines (3, 4%), vertebra (3, 4%), brain (1, 1.5%) and
      disseminated (2, 3%). Thus, extrapulmonary TB was more common in the cirrhotic
      patients as compared to pulmonary TB. Patients with Child's status A (n = 7)
      received 4 drugs (R: rifampicin, H: Isoniazid, E: ethambutol, Z: pyrizinamide)
      and could tolerate well even during follow up without any drug induced toxicity.
      In rest of patients commonest regimen followed was combination of drugs (RHEO, n
      = 32) followed by RHE (n = 11). DILI occurred in 35% started with either RHEO,
      HEO and REO. Median time of onset of DILI was 12 days (4-34) days. There was no
      DILI related death during hospital stay or follow up. CONCLUSIONS: Extrapulmonary
      TB is common in patients with cirrhosis and DILI is common in Child B and C with
      combination of rifampicin and isoniazid regimen.

PMID- 25941430
TI  - Study of the effects of cyclooxygenase-2 inhibitor on the promotion of hepatic
      tumorigenesis in rats fed a high fat diet.
AB  - BACKGROUND/OBJECTIVE: Hepatocellular carcinoma (HCC) is one of the most common
      malignant tumors worldwide. The highest prevalence of hepatitis is an important
      risk factor contributing to development of HCCs. However, an increasing number of
      cases are associated metabolic disease and steatohepatitis. Inflammation
      associated with many liver disease, seems to be a necessary pre-requisite for
      successful tumor initiation. Mechanisms that link high fat diet and inflammation
      initial stage of HCC are not completely understood. The present work was designed
      to investigate the effect of fat, through modulation of the insulin-like growth
      factors I and II (IGF-I and IGF-II), on the promotion of hepatocellular
      carcinoma, and the role of cyclooxygenase 2 (COX-2). METHODS: two main groups of
      rats were used: control and HCC groups. The HCC group was further sub-divide in
      to two subgroups, HCC fed with standard diet and HCC fed with high fat diet. The
      effects of celecoxib were also investigated in HCC fed with high fat diet.
      RESULTS: We found that high fat diet was associated with significant increases in
      COX2 and interleukin 6 (IL6) with significant promotion of HCC progression. The
      significant increase in IGF could contribute partially to the observed effects of
      high fat diet. In addition, celecoxib was found to significantly reduce HCC
      progression. CONCLUSIONS: We conclude that COX2 could play central role in high
      prevalence of HCC observed with high fat diet. Several triggering factors such as
      IGF and IL6, together with the direct modulation of fat metabolism could open
      several novel preventive strategies of celecoxib treatment, and could be useful
      biomarkers for assessment of its pharmacological effects.

PMID- 25941431
TI  - Portal vein thrombosis.
AB  - Portal vein thrombosis is an important cause of portal hypertension. PVT occurs
      in association with cirrhosis or as a result of malignant invasion by
      hepatocellular carcinoma or even in the absence of associated liver disease. With
      the current research into its genesis, majority now have an underlying
      prothrombotic state detectable. Endothelial activation and stagnant portal blood
      flow also contribute to formation of the thrombus. Acute non-cirrhotic PVT,
      chronic PVT (EHPVO), and portal vein thrombosis in cirrhosis are the three main
      variants of portal vein thrombosis with varying etiological factors and
      variability in presentation and management. Procoagulant state should be actively
      investigated. Anticoagulation is the mainstay of therapy for acute non-cirrhotic
      PVT, with supporting evidence for its use in cirrhotic population as well.
      Chronic PVT (EHPVO) on the other hand requires the management of portal
      hypertension as such and with role for anticoagulation in the setting of
      underlying prothrombotic state, however data is awaited in those with no
      underlying prothrombotic states. TIPS and liver transplant may be feasible even
      in the setting of PVT however proper selection of candidates and type of surgery
      is warranted. Thrombolysis and thrombectomy have some role. TARE is a new
      modality for management of HCC with portal vein invasion. 

PMID- 25941432
TI  - Pregnancy and vascular liver disease.
AB  - Vascular disorders of the liver frequently affect women of childbearing age.
      Pregnancy and the postpartum are prothrombotic states. Pregnancy seems to be a
      trigger for Budd-Chiari syndrome in patients with an underlying prothrombotic
      disorder. Whether pregnancy is a risk factor for other vascular liver disorders
      is unknown. In women with a known vascular liver disorder and a desire for
      pregnancy, stabilisation of the liver disease, including the use of a portal
      decompressive procedure when indicated, should be reached prior to conception.
      The presence of esophageal varices should be screened and adequate prophylaxis of
      bleeding applied in a manner similar to what is recommended for patients with
      cirrhosis. Most women likely benefit from anticoagulation during pregnancy and
      the postpartum. Labor and delivery are best managed by a multidisciplinary team
      with experience in this situation. Assisted vaginal delivery is the preferred
      mode of delivery. Although the risk of miscarriage and premature birth is
      heightened, current management of these diseases makes it very likely to see the
      birth of a live baby when pregnancy reaches 20 weeks of gestation. 

PMID- 25941435
TI  - Acute-on-Chronic Liver Failure: Recent Concepts.
AB  - A proportion of patients hospitalized for an acute complication of cirrhosis are
      at high risk of short-term death. The term Acute-on-Chronic Liver Failure (ACLF)
      is used to characterize these patients. Until recently there was no evidence
      based definition of ACLF. In 2013 a definition has been proposed based on results
      of a large prospective observational European study, called "European Association
      for the Study of the Liver (EASL)-Chronic Liver Failure (CLIF) Consortium Acute
      on-Chronic Liver Failure in Cirrhosis (CANONIC)" study. Results of this study led
      to elaborate new concepts about ACLF. First, it was found that ACLF is a syndrome
      that is distinct from mere decompensated cirrhosis. It was also shown that ACLF
      is a dynamic syndrome which can improve or conversely worsen. Patients who worsen
      die rapidly from multiorgan failures. The CANONIC study also found that
      identifiable precipitating events (e.g., bacterial infection, active alcoholism)
      are found in only 50% of cases of ACLF indicating that these events are
      dispensable for defining ACLF. In addition precipitating events may be initiators
      of ACLF but do not drive the outcome. An important concept derived from the
      CANONIC study is that ACLF is associated with systemic inflammation even in
      patients who do not have identifiable precipitating events. Finally it was found
      that ACLF may develop in patients without prior episodes of decompensation or in
      those with recent decompensation (<3 months). Moreover these patients with
      "early" ACLF were more severe than patients who developed ACLF after a long of
      history of decompensated cirrhosis. 

PMID- 25941434
TI  - Decellularization and cell seeding of whole liver biologic scaffolds composed of
      extracellular matrix.
AB  - The definitive treatment for patients with end-stage liver disease is orthotropic
      transplantation. However, this option is limited by the disparity between the
      number of patients needing transplantation and the number of available livers.
      This issue is becoming more severe as the population ages and as the number of
      new cases of end-stage liver failure increases. Patients fortunate enough to
      receive a transplant are required to receive immunosuppressive therapy and must
      live with the associated morbidity. Whole organ engineering of the liver may
      offer a solution to this liver donor shortfall. It has been shown that perfusion
      decellularization of a whole allogeneic or xenogeneic liver generates a three
      dimensional ECM scaffold with intact macro and micro architecture of the native
      liver. A decellularized liver provides an ideal transplantable scaffold with all
      the necessary ultrastructure and signaling cues for cell attachment,
      differentiation, vascularization, and function. In this review, an overview of
      complementary strategies for creating functional liver grafts suitable for
      transplantation is provided. Early milestones have been met by combining stem and
      progenitor cells with increasingly complex scaffold materials and culture
      conditions. 

PMID- 25941433
TI  - Non-alcoholic Fatty Liver Disease and Metabolic Syndrome-Position Paper of the
      Indian National Association for the Study of the Liver, Endocrine Society of
      India, Indian College of Cardiology and Indian Society of Gastroenterology.
AB  - Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic
      syndrome. Prevalence of metabolic risk factors including diabetes mellitus,
      obesity, etc. is rapidly increasing in India putting this population at risk for
      NAFLD. Patients with NAFLD are at increased risk for liver-related morbidity and
      mortality and also cardiovascular disease risk and increased incidence of
      diabetes mellitus on long-term follow-up. Management of patients with NAFLD may
      require a multi-disciplinary approach involving not only the hepatologists but
      also the internists, cardiologists, and endocrinologists. This position paper
      which is a combined effort of the Indian National Association for Study of the
      Liver (INASL), Endocrine Society of India (ESI), Indian College of Cardiology
      (ICC) and the Indian Society of Gastroenterology (ISG) defines the spectrum of
      NAFLD and the association of NAFLD with insulin resistance and metabolic syndrome
      besides suggesting preferred approaches for the diagnosis and management of
      patients with NAFLD in the Indian context. 

PMID- 25941436
TI  - Amoebic liver abscess with hepatic artery pseudoaneurysm: successful treatment by
      interventional radiology.
AB  - Amoebic liver abscess is most common extra-intestinal presentation of amoebiasis.
      It is rarely complicated with vascular involvement including thrombosis of
      hepatic vein or IVC and pseudo-aneurysm of hepatic artery. We describe a case of
      hepatic artery pseudo-aneurysm as a complication of amoebic liver abscess treated
      with percutaneous embolization. 

PMID- 25941437
TI  - Intrahepatic cholangiocarcinoma masquerading as liver abscess.
AB  - Malignancy masquerading as liver abscess, and presenting with fever, is mainly
      described in patients with colorectal cancers with liver metastasis. Primary
      liver tumors such as hepatocellular carcinoma or intrahepatic cholangiocarcinoma
      presenting as non-resolving liver abscess is extremely uncommon and carries a
      dismal prognosis. We present a rare case of non-resolving liver abscess as a
      presenting manifestation of intrahepatic cholangiocarcinoma. 

PMID- 25941438
TI  - Abdominal Pain Following Drug-eluting Bead Transarterial Chemoembolization.

PMID- 25941439
TI  - Antibiotics in Acute Liver Failure (ALF).

PMID- 25941440
TI  - Hepatobiliary quiz (answers)-13 (2015).

PMID- 25941441
TI  - Abdominal pain following drug-eluting bead transarterial chemoembolisation.

PMID- 25941442
TI  - A case of small intestinal hemorrhage secondary to metastatic lung cancer in the
      elderly.
AB  - Gastrointestinal metastasis from primary lung cancer is rare. In the present
      study, we report the case of a 78-year-old male who was admitted to the emergency
      department with acute bleeding of the digestive tract. During evaluation, he was
      found to have lung adenocarcinoma metastasis in the small bowel leading to
      hemorrhage. A jejunum wedge resection was carried out and bleeding was
      controlled. However, 2 months after the operation, the patient died from severe
      pulmonary infection. We also review the published literature of primary lung
      cancer with gastrointestinal metastasis. 

PMID- 25941444
TI  - A potential gender bias in assessing quality of life - a standard gamble
      experiment among university students.
AB  - BACKGROUND: There are several methodologies that can be used for evaluating
      patients' perception of their quality of life. Most commonly, utilities are
      directly elicited by means of either the time-trade-off or the standard-gamble
      method. In both methods, risk attitudes determine the quality of life values.
      METHODS: Quality of life values among 31 Austrian undergraduate students were
      elicited by means of the standard gamble approach. The impact of several
      variables such as gender, side job, length of study, and living arrangements on
      the quality of life were identified using different types of regression
      techniques (ordinary least squares, generalized linear model, Betafit). RESULTS:
      Significant evidence was found that females are associated with a higher quality
      of life in all specifications of our estimations. DISCUSSION: The observed gender
      differences in quality of life can be attributed to a higher degree of risk
      aversion of women. A higher risk aversion leads to a higher valuation of given
      health states and a potential gender bias in health economic evaluations. This
      result could have implications for health policy planners when it comes to budget
      allocation decisions.

PMID- 25941443
TI  - Physical exercise and functional fitness in independently living vs
      institutionalized elderly women: a comparison of 60- to 79-year-old city
      dwellers.
AB  - PURPOSE: To compare functional fitness (FF) levels among independent-living (IL)
      and day care (DC) elderly women of different age groups and to analyze changes in
      FF after 8 months of participation in an exercise program intervention for the IL
      elderly women. MATERIALS AND METHODS: A total of 674 elderly women were divided
      into four IL groups with age in the range of 60-64 years (IL60-64, n=149), 65-69
      years (IL65-69, n=138), 70-74 years (IL70-74, n=135), and 75-79 years (IL75-79,
      n=83), and four DC groups with age in the range of 60-64 years (DC60-64, n=35),
      65-69 years (DC65-69, n=34), 70-74 years (DC70-74, n=47), and 75-79 years (DC75
      79, n=53). The intervention consisted of a multimodal exercise training, 3 days
      per week for 8 months. Senior Fitness Test battery performances were obtained at
      baseline and after 8-month intervention. RESULTS: Significant differences were
      identified between all IL groups and DC groups in all FF tests (P<0.001), except
      between IL70-74 and DC70-74 in the chair sit-and-reach. Analysis of covariance
      (ANCOVA) identified significant improvements in all FF tests between pre- and
      posttests in the IL groups (P<0.001), except in the chair sit-and-reach for the
      IL70-74. ANCOVA also showed a significant declining performance in all FF tests
      for DC groups (P<0.001), except in the chair sit-and-reach for the DC70-74 and
      DC75-79. CONCLUSION: IL women are more fit than institutionalized DC elderly
      women. The multimodal training was effective in improving all FF components
      related to daily living activities, in all age groups. In contrast,
      institutionalized elderly showed a clear tendency to worsen their FF over the
      time.

PMID- 25941445
TI  - TriCalm((r)) hydrogel is significantly superior to 2% diphenhydramine and 1%
      hydrocortisone in reducing the peak intensity, duration, and overall magnitude of
      cowhage-induced itch.
AB  - BACKGROUND: Itch is one of the most frequent skin complaints and its treatment is
      challenging. From a neurophysiological perspective, two distinct peripheral and
      spinothalamic pathways have been described for itch transmission: a histaminergic
      pathway and a nonhistaminergic pathway mediated by protease-activated receptors
      (PAR)2 and 4. The nonhistaminergic itch pathway can be activated exogenously by
      spicules of cowhage, a tropical plant that releases a cysteine protease named
      mucunain that binds to and activates PAR2 and PAR4. PURPOSE: This study was
      conducted to assess the antipruritic effect of a novel over-the-counter (OTC)
      steroid-free topical hydrogel formulation, TriCalm((r)), in reducing itch
      intensity and duration, when itch was induced with cowhage, and compared it with
      two other commonly used OTC anti-itch drugs. STUDY PARTICIPANTS AND METHODS: This
      double-blinded, vehicle-controlled, randomized, crossover study recorded itch
      intensity and duration in 48 healthy subjects before and after skin treatment
      with TriCalm hydrogel, 2% diphenhydramine, 1% hydrocortisone, and hydrogel
      vehicle, used as a vehicle control. RESULTS: TriCalm hydrogel significantly
      reduced the peak intensity and duration of cowhage-induced itch when compared to
      the control itch curve, and was significantly superior to the two other OTC
      antipruritic agents and its own vehicle in antipruritic effect. TriCalm hydrogel
      was eight times more effective than 1% hydrocortisone and almost six times more
      effective than 2% diphenhydramine in antipruritic action, as evaluated by the
      reduction of area under the curve. CONCLUSION: TriCalm hydrogel has a robust
      antipruritic effect against nonhistaminergic pruritus induced via the PAR2
      pathway, and therefore it could represent a promising treatment option for itch.

PMID- 25941447
TI  - Re-establishment of Carabus (Cathoplius) aliai Escalera, 1944 as a separate valid
      species (Coleoptera, Carabidae).
AB  - Carabus (Cathoplius) aliai was described as a separate species by Escalera in
      1944 but since the 1950-60s it has been considered as a subspecies of Carabus
      (Cathoplius) stenocephalus Lucas, 1866. This downgrading was adopted after
      examining only a few specimens, due to their rarity in collections. In recent
      years, an important population of this taxon was rediscovered in the Tan-Tan area
      in southern Morocco. By combining field observations with laboratory breeding
      experiments including hybridization trials, and through the morphological
      examination of a representative number of individuals, it is confirmed that
      Carabusaliai is indeed a valid species. Despite close geographic distribution,
      the morphological and biological characteristics of Carabusaliai and
      Carabusstenocephalusifniensis Zarco, 1941, its northern substitutive taxon, are
      very different. Carabusaliai adults are characterized by a smaller size, a
      slender silhouette, a more brilliant aspect, a narrower pronotum, a coarser
      elytral sculpture, longer legs, and a wider and a little more curved apex of the
      median lobe of the aedeagus. Carabusaliai larvae are also characterized by a much
      smaller size and the Carabusaliai pupa has a narrower thoracic area and a
      different chaetotaxy compared to that of Carabusstenocephalusifniensis. Contrary
      to this, Carabusaliai has a life cycle belonging to the annual univoltine winter
      semelparous type. Moreover, the duration of its development cycle is shorter.
      Carabusaliai is a sabulicolous steppe-wandering species with an intensive running
      activity, while Carabusstenocephalusifniensis is a more sedentary taxon.
      Crossbreeding experiments showed a marked reproductive isolation between
      Carabusaliai and Carabusstenocephalusifniensis. When F1 hybrids were crossed with
      one another, a very high mortality rate during embryonic, larval and pupal
      development was evident and no vital F2 neo-adults were obtained. Morphological
      and biological differences, together with the reproductive failure in
      Carabusaliai * Carabusstenocephalusifniensis hybrids, clearly indicate that
      Carabusaliai is a separate Cathoplius species that is distributed in an area
      south of the Anti-Atlas chain, from Plage Blanche (Guelmim) to Lemsid and Bou Kra
      (south of Laayoune). Carabusaliai is therefore both a Saharan desert endemic and
      an Atlantic resident. Moreover, it is the southernmost Carabus species of the
      western Palaearctic region. 

PMID- 25941446
TI  - Role of the WASP and WAVE family proteins in breast cancer invasion and
      metastasis.
AB  - The Wiskott-Aldrich syndrome protein (WASP) and WASP family verprolin-homologous
      protein (WAVE) family are a group of molecules that form a key link between
      GTPases and the actin cytoskeleton. The role of WASP/WAVE family proteins in the
      control of actin polymerization through activation of the actin-related protein
      2/3 complex is critical in the formation of the actin-based membrane protrusions
      seen in cell migration and invasion. For this reason, the activity of the
      WASP/WAVE family in cancer cell invasion and migration has been of great interest
      in recent years. Many reports have highlighted the potential of targeting the
      WASP/WAVE family as a therapy for the prevention of cancer progression, in
      particular breast cancer. This review focuses on the role of the WASP/WAVE family
      in breast cancer cell invasion and migration and how this relates to the
      molecular mechanisms of WASP/WAVE activity, their exact contributions to the
      stages of cancer progression, and how this can lead to the development of
      anticancer drugs that target the WASP/WAVE family and related pathways. 

PMID- 25941448
TI  - Two new species of Indigofera L. (Leguminosae) from the Sneeuberg Centre of
      Floristic Endemism, Great Escarpment (Eastern and Western Cape, South Africa).
AB  - Two new species of Indigofera L. (Leguminosae) are described from the Sneeuberg
      Centre of Floristic Endemism on the southern Great Escarpment, Eastern and
      Western Cape Provinces, South Africa. Both species are localised high-altitude
      endemics. Indigoferamagnifica Schrire & V.R. Clark is confined to the summit
      plateau of the Toorberg-Koudeveldberg-Meelberg west of Graaff-Reinet, and
      complements other western Sneeuberg endemics such as Ericapasserinoides (Bolus)
      E.G.H. Oliv. and Faurearecondita Rourke & V.R. Clark. Indigoferaasantasanensis
      Schrire & V.R. Clark is confined to a small area east of Graaff-Reinet, and
      complements several other eastern Sneeuberg endemics such as Euryopsexsudans B.
      Nord & V.R. Clark and Euryopsproteoides B. Nord. & V.R. Clark. Based on
      morphology, both new species belong to the Cape Clade of Indigofera, supporting a
      biogeographical link between the Cape Floristic Region and the Sneeuberg, as well
      as with the rest of the eastern Great Escarpment. 

PMID- 25941449
TI  - Grassroots e-floras in the Poaceae: growing GrassBase and GrassWorld.
AB  - GrassBase and GrassWorld are the largest structured descriptive datasets in
      plants, publishing descriptions of 11,290 species in the DELTA format. Twenty
      nine years of data compilation and maintenance have created a dataset which now
      underpins much of the Poaceae bioinformatics. GrassBase and GrassWorld can
      continue to grow productively if the proliferation of alternative classifications
      and datasets can be brought together into a consensus system. If the datasets are
      reconciled instead of diverging further apart a long term cumulative process can
      bring knowledge together for great future utility. This paper presents the
      Poaceae as the first and largest model system for e-taxonomy and the study of
      classification development in plants. The origin, development, and content of
      both datasets is described and key contributors are noted. The challenges of
      alternative classifications, data divergence, collaborative contribution
      mechanisms, and software are outlined. 

PMID- 25941450
TI  - Fauna europaea: neuropterida (raphidioptera, megaloptera, neuroptera).
AB  - Fauna Europaea provides a public web-service with an index of scientific names of
      all living European land and freshwater animals, their geographical distribution
      at country level (up to the Urals, excluding the Caucasus region), and some
      additional information. The Fauna Europaea project covers about 230,000 taxonomic
      names, including 130,000 accepted species and 14,000 accepted subspecies, which
      is much more than the originally projected number of 100,000 species. This
      represents a huge effort by more than 400 contributing specialists throughout
      Europe and is a unique (standard) reference suitable for many users in science,
      government, industry, nature conservation and education. For Neuropterida, data
      from three Insect orders (Raphidioptera, Megaloptera, Neuroptera), comprising 15
      families and 397 species, are included. 

PMID- 25941451
TI  - Taxa and names in Cynoglossum sensu lato (Boraginaceae, Cynoglosseae): an
      annotated, synonymic inventory, with links to the protologues and mention of
      original material.
AB  - BACKGROUND: An inventory is presented of all names so far validly published in
      Cynoglossum sensu lato and its segregate genera: Adelocaryum, Afrotysonia,
      Kuschakewiczia, Lindelofia, Mattiastrum, Paracaryum, Rindera, Solenanthus,
      Trachelanthus, and their synonyms. Names and designations that were not validly
      published in the cited place, and later isonyms, are accounted for when they have
      been included in the International Plant Name Index (IPNI). Problems with IPNI
      entries, including errors and omissions, are discussed, and the hope is expressed
      that the present inventory may be of use for fixing them. NEW INFORMATION: The
      inventory, generated from a list of structured data, is presented in two
      Supplements, as a searchable HTML document comprising a sequence of entries with
      internal cross-links and links to external sources, in particular to protologues
      accessible online or, copyright restrictions permitting, made available as
      scanned documents via DOIs, and as machine-readible file. With minor exceptions,
      all names have been verified in their original place of publication, and all were
      nomenclaturally assessed. Colour coding is used to distinguish between names (in
      green) pertaining to Cynoglossum sensu lato, for which complete synonymies are
      provided; and names (in orange) pertaining to other genera but published under
      Cynoglossum or its segregates. They are listed together with their basionym and
      the corresponding correct name (if it exists), but without complete synonymy.
      Acceptable, potentially correct names appear in bold-face type, both under a
      broadly defined Cynoglossum (for which purpose validation of 81 new combinations
      and the name of 1 new species was necessary) and under one or more of its
      segregates. When a name was published for a new taxon, original material is
      indicated, usually by direct quotation from the protologue. New type designations
      are exceptional (two cases), whereas former type designations are cited whenever
      known. Furthermore, types and original specimens, especially when their digital
      images are available online, are mentioned with their locations and accession
      numbers. Comments are added whenever appropriate, especially to explain
      nomenclatural assessments that are not self-evident.

PMID- 25941452
TI  - Black flies (Diptera: Simuliidae) of Turkish Thrace, with a new record for
      Turkey.
AB  - BACKGROUND: This paper includes 2742 specimens of 18 species of black flies
      (Diptera: Simuliidae) collected from 132 lotic sites in Turkish Thrace, the
      European part of Turkey, in the early summer of 2002 and 2003 and the spring of
      2005 and 2006. NEW INFORMATION: All species are recorded from this region for the
      first time, and Metacnephianigra (Rubtsov, 1940) is a new record for Turkey.
      Distributional and taxonomical remarks are given for each species.

PMID- 25941453
TI  - Extending marine species distribution maps using non-traditional sources.
AB  - BACKGROUND: Traditional sources of species occurrence data such as peer-reviewed
      journal articles and museum-curated collections are included in species databases
      after rigorous review by species experts and evaluators. The distribution maps
      created in this process are an important component of species survival
      evaluations, and are used to adapt, extend and sometimes contract polygons used
      in the distribution mapping process. NEW INFORMATION: During an IUCN Red List
      Gulf of Mexico Fishes Assessment Workshop held at The Harte Research Institute
      for Gulf of Mexico Studies, a session included an open discussion on the topic of
      including other sources of species occurrence data. During the last decade,
      advances in portable electronic devices and applications enable 'citizen
      scientists' to record images, location and data about species sightings, and
      submit that data to larger species databases. These applications typically
      generate point data. Attendees of the workshop expressed an interest in how that
      data could be incorporated into existing datasets, how best to ascertain the
      quality and value of that data, and what other alternate data sources are
      available. This paper addresses those issues, and provides recommendations to
      ensure quality data use.

PMID- 25941454
TI  - Luzonichthysseaver, a new species of Anthiinae (Perciformes, Serranidae) from
      Pohnpei, Micronesia.
AB  - Luzonichthysseaver, n. sp., is described from two specimens, 42-46 mm standard
      length (SL) collected from Pohnpei, Micronesia. Collections were made by divers
      on mixed-gas closed-circuit rebreathers using hand nets at depths of 90-100 m.
      Luzonichthysseaver is distinct from all other species of the genus in the
      characters of lateral line scales, gill rakers, pelvic fin length, caudal
      concavity and coloration. Of the six species of Luzonichthys, it appears to be
      morphologically most similar to L.earlei and L.whitleyi. 

PMID- 25941455
TI  - Inventory of the Heteroptera (Insecta: Hemiptera) in Komaba Campus of the
      University of Tokyo, a highly urbanized area in Japan.
AB  - BACKGROUND: The Heteroptera, or true bugs, forms one of the major insect groups
      with respect to the very diverse habitat preferences, including both aquatic and
      terrestrial species, as well as a variety of feeding types. The first
      comprehensive inventory of the Heteroptera at Komaba Campus of the University of
      Tokyo, or an urban green space in the center of the Tokyo Metropolis, Japan, was
      conducted. NEW INFORMATION: A total of 115 species in 29 families of the suborder
      Heteroptera were identified. The area had a high species richness compared with
      other urbanized and suburbanized localities in Tokyo. The campus is found to show
      a substantial difference in heteropteran species compositions, despite being
      close to the other localities surrounded by highly urbanized zones in central
      Tokyo.

PMID- 25941456
TI  - First record of Limnatispaluda (Hirudinida, Arhynchobdellida, Praobdellidae) from
      Kazakhstan, with comments on genetic diversity of Limnatis leeches.
AB  - BACKGROUND: Sawyer (1986) included three species in the nasal leech genus
      LimnatisMoquin-Tandon 1827: Limnatisnilotica (Savigny 1822),
      LimnatisbacescuiManoleli 1972 and Limnatispaluda (Tennent 1859). The first and
      last species have mainly been identified in Middle Eastern countries (e.g.
      Kinzelbach and Ruckert 1985). The second species has been identified only in
      Romania Dobruja (Manoleli 1972). Although Limnatis leeches are well known species
      of endoparasitic leeches, Limnatisnilotica was recorded only once in Kazakhstan
      (Lukin 1976). NEW INFORMATION: Specimens of the genus Limnatis from Almaty
      Province, Kazakhstan are identified as Limnatispaluda. This is the first record
      of Limnatispaluda from Kazakhstan. Mitochondrial COI and 12S data demonstrated
      that the present specimens are genetically close to an Israeli specimen
      identified as Limnatisnilotica. In addition, molecular data suggest that some
      Limnatis specimens whose DNA sequences have been reported were misidentified.
      According to the observed phylogenetic relationships, the taxonomic status of the
      known Limnatis species should be revisited.

PMID- 25941457
TI  - Neuroscience and Brain Science Special Issue begins in the Malaysian Journal of
      Medical Sciences.
AB  - The Malaysian Journal of Medical Sciences and the Orient Neuron Nexus have
      amalgated to publish a yearly special issue based on neuro- and brain sciences.
      This will hopefully improve the quality of peer-reviewed manuscripts in the field
      of fundamental, applied, and clinical neuroscience and brain science from Asian
      countries. One focus of the Universiti Sains Malaysia is to strengthen
      neuroscience and brain science, especially in the field of neuroinformatics. 

PMID- 25941458
TI  - Evaluation of the Cytotoxicity of Levodopa and its Complex with Hydroxypropyl
      beta-Cyclodextrin (HP-beta-CD) to an Astrocyte Cell Line.
AB  - A simple, reliable a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2
      (4-sulfophenyl)-2H-tetrazolium, (MTS) assay was conducted to evaluate the
      potential cytotoxic effects of levodopa, a "gold standard therapy" for
      Parkinsonism, and its complex with Hydroxypropyl-beta-Cyclodextrin (HP-beta-CD)
      on an astrocyte cell line. The cells were incubated in a range of concentrations
      from 4.69 to 300 MUg/mL levodopa, HP-beta-CD or the complex for up to 72 hours.
      At every 24-hour interval, the optical density (OD), which reflects the number of
      viable cells, was recorded. In general, linear dose-dependent cytotoxicity
      profiles were observed for the cells subjected to levodopa or the complex,
      whereas a slightly triphasic response was observed for the cells exposed to HP
      beta-CD. A significant difference (P < 0.05) in cytotoxicity was detected between
      the HP-beta-CD-treated group and the levodopa-treated group. In particular, we
      observed that the cells treated with the complex, even at the highest
      concentrations (> 200 MUg/mL), exhibited improved tolerability in a time
      dependent manner, which may indicate the potential ability of HP-beta-CD to mask
      the toxic effects of levodopa via complexation. 

PMID- 25941459
TI  - In vivo Electrochemical Biosensor for Brain Glutamate Detection: A Mini Review.
AB  - Glutamate is one of the most prominent neurotransmitters in mammalian brains,
      which plays an important role in neuronal excitation. High levels of
      neurotransmitter cause numerous alterations, such as calcium overload and the
      dysfunction of mitochondrial and oxidative stress. These alterations may lead to
      excitotoxicity and may trigger multiple neuronal diseases, such as Alzheimer's
      disease, stroke, and epilepsy. Excitotoxicity is a pathological process that
      damages nerve cells and kills cells via excessive stimulation by
      neurotransmitters. Monitoring the concentration level of brain glutamate via an
      implantable microbiosensor is a promising alternative approach to closely
      investigate in the function of glutamate as a neurotransmitter. This review
      outlines glutamate microbiosensor designs to enhance the sensitivity of glutamate
      detection with less biofouling occurrence and minimal detection of interference
      species. There are many challenges in the development of a reproducible and
      stable implantable microbiosensor because many factors and limitations may affect
      the detection performance. However, the incorporation of multiple scales is
      needed to address the basic issues and combinations across the various
      disciplines needed to achieve the success of the system to overcome the
      challenges in the development of an implantable glutamate biosensor. 

PMID- 25941460
TI  - MiR-3099 is Overexpressed in Differentiating 46c Mouse Embryonic Stem Cells upon
      Neural Induction.
AB  - BACKGROUND: MicroRNAs (miRNAs) have a crucial role in gene expression regulation
      and protein synthesis, especially in the central nervous system. In developing
      mouse embryos a novel miRNA, miR-3099, is highly expressed, particularly in the
      central nervous system. This study aims to determine the expression of miR-3099
      during cellular differentiation of 46C mouse embryonic stem cells after neural
      induction with N2/B27 medium. METHODS: 46C mouse embryonic stem cells were
      subjected to neural induction with N2/B27 medium. At 0, 3, 7, 11, 17, and 22 days
      after neural induction, the cells were screened for various pluripotent,
      progenitor, and differentiating/differentiated cells markers by
      immunocytochemistry and reverse-transcriptase polymerase chain reaction (RT-PCR).
      Stem-loop pulse RT-PCR was performed to determine the expression of miR-3099 at
      all selected time points after neural induction. RESULTS: Our findings showed
      that after induction, mouse embryonic stem cells differentiated into
      heterogeneous pools of cells containing neurons, astrocytes, and
      oligodendrocytes. Mouse embryonic stem cells and neural progenitor/precursor
      cells were also present in culture up to day 22 as indicated by RT-PCR analysis.
      Elucidation of miR-3099 expression during in vitro neural induction revealed that
      this miRNA was expressed throughout the differentiation process of 46C mouse
      embryonic stem cells. miR-3099 was expressed at higher levels on day 11, 17, and
      22 as compared to day 0, 3 and 7 after neural induction. CONCLUSION: The level of
      miR-3099 expression was higher in differentiated mouse embryonic stem cells after
      neural induction. This finding suggested that miR-3099 might play a role in
      regulating neural stem cell differentiation. However, further characterisation of
      miR-3099 in a better characterised or optimised differentiated neural stem cell
      culture would provide increased understanding of the cellular function and
      molecular targets of miR-3099, especially in neuron development.

PMID- 25941461
TI  - Age-dependent Electroencephalographic Differences in the Genetic Absence Epilepsy
      Rats from Strasbourg (GAERS) Model of Absence Epilepsy.
AB  - Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are a prognostic genetic
      model of absence epilepsy. This model displays the electro-clinical, behavioural,
      and pharmacological features of absence seizures. Although GAERS share typical
      characteristics, including spike-and-wave discharges (SWDs) in the
      electroencephalography (EEG), age-dependent studies with these animals have not
      yet been reported. The aim of the present study is to perform a systematic
      comparison contrasting the SWDs of young and older GAERS, in terms of the number,
      duration, frequency, and waveform morphology of the discharges, as well as the
      pre-SWD EEG characteristics, using identical measurement and analysis techniques.
      The number, cumulative total duration and mean duration of SWDs were
      significantly higher in young GAERS (4 to 6 months) compared to older GAERS (12
      to 14 months). Furthermore, the SWD spectra and average SWD waveforms indicated
      that a single cycle of the SWD contains more energy in faster components, such as
      increased spikes and higher power, in the SWDs of the young GAERS. Additionally,
      older GAERS showed weak amplitude spikes in SWDs and higher power pre-SWDs. These
      clear morphological differences in the EEGs of young and older GAERS rats should
      be further examined in future studies that explore new dimensions of genetic
      absence epilepsy. 

PMID- 25941462
TI  - Effect of hypobaric hypoxia on cognitive functions and potential therapeutic
      agents.
AB  - High altitude (HA), defined as approximately 3000-5000 m, considerably alters
      physiological and psychological parameters within a few hours. Chronic HA
      mediated hypoxia (5000 m) results in permanent neuronal damage to the human brain
      that persists for one year or longer, even after returning to sea level. At HA,
      there is a decrease in barometric pressure and a consequential reduction in the
      partial pressure of oxygen (PO2), an extreme environmental condition to which
      humans are occasionally exposed. This condition is referred to as hypobaric
      hypoxia (HBH), which represents the most unfavourable characteristics of HA. HBH
      causes the disruption of oxygen availability to tissue. However, no review
      article has explored the impact of HBH on cognitive functions or the potential
      therapeutic agents for HBH. Therefore, the present review aimed to describe the
      impact of HBH on both physiological and cognitive functions, specifically
      learning and memory. Finally, the potential therapeutic agents for the treatment
      of HBH-induced cognitive impairment are discussed. 

PMID- 25941464
TI  - Abstracts of orient neuron nexus 1(1), 2(1), and 3(1).

PMID- 25941463
TI  - The brain in pain.
AB  - Pain, while salient, is highly subjective. A sensation perceived as painful by
      one person may be perceived as uncomfortable, not painful or even pleasant to
      others. Within the same person, pain may also be modulated according to its
      threat value and the context in which it is presented. Imaging techniques, such
      as functional magnetic resonance imaging and positron emission tomography, have
      identified a distributed network in the brain, the pain-relevant brain regions,
      that encode the sensory-discriminative aspect of pain, as well as its cognitive
      and affective/emotional factors. Current knowledge also implicates the prefrontal
      cortex as the modulatory area for pain, with its subdivisions forming the cortico
      cortical pathway, an alternative pain modulatory pathway distinct from the
      descending modulatory pathway of pain. These findings from neuroimaging in human
      subjects have paved the way for the molecular mechanisms of pain modulation to be
      explored in animal studies. 

PMID- 25941465
TI  - Identification of protein-ligand binding sites by the level-set variational
      implicit-solvent approach.
AB  - Protein-ligand binding is a key biological process at the molecular level. The
      identification and characterization of small-molecule binding sites on
      therapeutically relevant proteins have tremendous implications for target
      evaluation and rational drug design. In this work, we used the recently developed
      level-set variational implicit-solvent model (VISM) with the Coulomb field
      approximation (CFA) to locate and characterize potential protein-small-molecule
      binding sites. We applied our method to a data set of 515 protein-ligand
      complexes and found that 96.9% of the cocrystallized ligands bind to the VISM-CFA
      identified pockets and that 71.8% of the identified pockets are occupied by
      cocrystallized ligands. For 228 tight-binding protein-ligand complexes (i.e,
      complexes with experimental pKd values larger than 6), 99.1% of the
      cocrystallized ligands are in the VISM-CFA-identified pockets. In addition, it
      was found that the ligand binding orientations are consistent with the
      hydrophilic and hydrophobic descriptions provided by VISM. Quantitative
      characterization of binding pockets with topological and physicochemical
      parameters was used to assess the "ligandability" of the pockets. The results
      illustrate the key interactions between ligands and receptors and can be very
      informative for rational drug design.

PMID- 25941466
TI  - Costs of switching auditory spatial attention in following conversational turn
      taking.
AB  - Following a multi-talker conversation relies on the ability to rapidly and
      efficiently shift the focus of spatial attention from one talker to another. The
      current study investigated the listening costs associated with shifts in spatial
      attention during conversational turn-taking in 16 normally-hearing listeners
      using a novel sentence recall task. Three pairs of syntactically fixed but
      semantically unpredictable matrix sentences, recorded from a single male talker,
      were presented concurrently through an array of three loudspeakers (directly
      ahead and +/-30 degrees  azimuth). Subjects attended to one spatial location,
      cued by a tone, and followed the target conversation from one sentence to the
      next using the call-sign at the beginning of each sentence. Subjects were
      required to report the last three words of each sentence (speech recall task) or
      answer multiple choice questions related to the target material (speech
      comprehension task). The reading span test, attention network test, and trail
      making test were also administered to assess working memory, attentional control,
      and executive function. There was a 10.7 +/- 1.3% decrease in word recall, a
      pronounced primacy effect, and a rise in masker confusion errors and word
      omissions when the target switched location between sentences. Switching costs
      were independent of the location, direction, and angular size of the spatial
      shift but did appear to be load dependent and only significant for complex
      questions requiring multiple cognitive operations. Reading span scores were
      positively correlated with total words recalled, and negatively correlated with
      switching costs and word omissions. Task switching speed (Trail-B time) was also
      significantly correlated with recall accuracy. Overall, this study highlights (i)
      the listening costs associated with shifts in spatial attention and (ii) the
      important role of working memory in maintaining goal relevant information and
      extracting meaning from dynamic multi-talker conversations. 

PMID- 25941467
TI  - Neuropsychiatric disorders in Cushing's syndrome.
AB  - Endogenous Cushing's syndrome (CS), a rare endocrine disorder characterized by
      cortisol hypersecretion, is associated with psychiatric and neurocognitive
      disorders. Major depression, mania, anxiety, and neurocognitive impairment are
      the most important clinical abnormalities. Moreover, patients most often complain
      of impairment in quality of life, interference with family life, social, and work
      performance. Surprisingly, after hypercortisolism resolution, despite the
      improvement of the overall prevalence of psychiatric and neurocognitive
      disorders, the brain volume loss at least partially persists and it should be
      noted that some patients may still display depression, anxiety, panic disorders,
      and neurocognitive impairment. This brief review aimed at describing the
      prevalence of psychiatric and neurocognitive disorders and their characterization
      both during the active and remission phases of CS. The last section of this
      review is dedicated to quality of life, impaired during active CS and only
      partially resolved after resolution of hypercortisolism. 

PMID- 25941468
TI  - Using a motion capture system for spatial localization of EEG electrodes.
AB  - Electroencephalography (EEG) is often used in source analysis studies, in which
      the locations of cortex regions responsible for a signal are determined. For this
      to be possible, accurate positions of the electrodes at the scalp surface must be
      determined, otherwise errors in the source estimation will occur. Today, several
      methods for acquiring these positions exist but they are often not satisfyingly
      accurate or take a long time to perform. Therefore, in this paper we describe a
      method capable of determining the positions accurately and fast. This method uses
      an infrared light motion capture system (IR-MOCAP) with 8 cameras arranged around
      a human participant. It acquires 3D coordinates of each electrode and
      automatically labels them. Each electrode has a small reflector on top of it thus
      allowing its detection by the cameras. We tested the accuracy of the presented
      method by acquiring the electrodes positions on a rigid sphere model and
      comparing these with measurements from computer tomography (CT). The average
      Euclidean distance between the sphere model CT measurements and the presented
      method was 1.23 mm with an average standard deviation of 0.51 mm. We also tested
      the method with a human participant. The measurement was quickly performed and
      all positions were captured. These results tell that, with this method, it is
      possible to acquire electrode positions with minimal error and little time effort
      for the study participants and investigators. 

PMID- 25941469
TI  - Responses of neurons in the marmoset primary auditory cortex to interaural level
      differences: comparison of pure tones and vocalizations.
AB  - Interaural level differences (ILDs) are the dominant cue for localizing the
      sources of high frequency sounds that differ in azimuth. Neurons in the primary
      auditory cortex (A1) respond differentially to ILDs of simple stimuli such as
      tones and noise bands, but the extent to which this applies to complex natural
      sounds, such as vocalizations, is not known. In sufentanil/N2O anesthetized
      marmosets, we compared the responses of 76 A1 neurons to three vocalizations
      (Ock, Tsik, and Twitter) and pure tones at cells' characteristic frequency. Each
      stimulus was presented with ILDs ranging from 20 dB favoring the contralateral
      ear to 20 dB favoring the ipsilateral ear to cover most of the frontal azimuthal
      space. The response to each stimulus was tested at three average binaural levels
      (ABLs). Most neurons were sensitive to ILDs of vocalizations and pure tones. For
      all stimuli, the majority of cells had monotonic ILD sensitivity functions
      favoring the contralateral ear, but we also observed ILD sensitivity functions
      that peaked near the midline and functions favoring the ipsilateral ear.
      Representation of ILD in A1 was better for pure tones and the Ock vocalization in
      comparison to the Tsik and Twitter calls; this was reflected by higher
      discrimination indices and greater modulation ranges. ILD sensitivity was heavily
      dependent on ABL: changes in ABL by +/-20 dB SPL from the optimal level for ILD
      sensitivity led to significant decreases in ILD sensitivity for all stimuli,
      although ILD sensitivity to pure tones and Ock calls was most robust to such ABL
      changes. Our results demonstrate differences in ILD coding for pure tones and
      vocalizations, showing that ILD sensitivity in A1 to complex sounds cannot be
      simply extrapolated from that to pure tones. They also show A1 neurons do not
      show level-invariant representation of ILD, suggesting that such a representation
      of auditory space is likely to require population coding, and further processing
      at subsequent hierarchical stages. 

PMID- 25941470
TI  - On event-based optical flow detection.
AB  - Event-based sensing, i.e., the asynchronous detection of luminance changes,
      promises low-energy, high dynamic range, and sparse sensing. This stands in
      contrast to whole image frame-wise acquisition by standard cameras. Here, we
      systematically investigate the implications of event-based sensing in the context
      of visual motion, or flow, estimation. Starting from a common theoretical
      foundation, we discuss different principal approaches for optical flow detection
      ranging from gradient-based methods over plane-fitting to filter based methods
      and identify strengths and weaknesses of each class. Gradient-based methods for
      local motion integration are shown to suffer from the sparse encoding in address
      event representations (AER). Approaches exploiting the local plane like structure
      of the event cloud, on the other hand, are shown to be well suited. Within this
      class, filter based approaches are shown to define a proper detection scheme
      which can also deal with the problem of representing multiple motions at a single
      location (motion transparency). A novel biologically inspired efficient motion
      detector is proposed, analyzed and experimentally validated. Furthermore, a stage
      of surround normalization is incorporated. Together with the filtering this
      defines a canonical circuit for motion feature detection. The theoretical
      analysis shows that such an integrated circuit reduces motion ambiguity in
      addition to decorrelating the representation of motion related activations. 

PMID- 25941471
TI  - Astrocytes increase the activity of synaptic GluN2B NMDA receptors.
AB  - Astrocytes regulate excitatory synapse formation and surface expression of
      glutamate AMPA receptors (AMPARs) during development. Less is known about glial
      modulation of glutamate NMDA receptors (NMDARs), which mediate synaptic
      plasticity and regulate neuronal survival in a subunit- and subcellular
      localization-dependent manner. Using primary hippocampal cultures with mature
      synapses, we found that the density of NMDA-evoked whole-cell currents was
      approximately twice as large in neurons cultured in the presence of glia compared
      to neurons cultured alone. The glial effect was mediated by (an) astrocyte
      secreted soluble factor(s), was Mg(2+) and voltage independent, and could not be
      explained by a significant change in the synaptic density. Instead, we found that
      the peak amplitudes of total and NMDAR miniature excitatory postsynaptic currents
      (mEPSCs), but not AMPAR mEPSCs, were significantly larger in mixed than neuronal
      cultures, resulting in a decreased synaptic AMPAR/NMDAR ratio. Astrocytic
      modulation was restricted to synaptic NMDARs that contain the GluN2B subunit, did
      not involve an increase in the cell surface expression of NMDAR subunits, and was
      mediated by protein kinase C (PKC). Taken together, our findings indicate that
      astrocyte-secreted soluble factor(s) can fine-tune synaptic NMDAR activity
      through the PKC-mediated regulation of GluN2B NMDAR channels already localized at
      postsynaptic sites, presumably on a rapid time scale. Given that physiologic
      activation of synaptic NMDARs is neuroprotective and that an increase in the
      synaptic GluN2B current is associated with improved learning and memory, the
      astrocyte-induced potentiation of synaptic GluN2B receptor activity is likely to
      enhance cognitive function while simultaneously strengthening neuroprotective
      signaling pathways. 

PMID- 25941474
TI  - Netrin-5 is highly expressed in neurogenic regions of the adult brain.
AB  - Mammalian netrin family proteins are involved in targeting of axons, neuronal
      migration, and angiogenesis and act as repulsive and attractive guidance
      molecules. Netrin-5 is a new member of the netrin family with homology to the
      C345C domain of netrin-1. Unlike other netrin proteins, murine netrin-5 consists
      of two EGF motifs of the laminin V domain (LE) and the C345C domain, but lacks
      the N-terminal laminin VI domain and one of the three LE motifs. We generated a
      specific antibody against netrin-5 to investigate its expression pattern in the
      rodent adult brain. Strong netrin-5 expression was observed in the olfactory bulb
      (OB), rostral migrate stream (RMS), the subventricular zone (SVZ), and the
      subgranular zone (SGZ) of the dentate gyrus in the hippocampus, where
      neurogenesis occurs in the adult brain. In the SVZ and RMS, netrin-5 expression
      was observed in Mash1-positive transit-amplifying cells and in Doublecortin (DCX)
      positive neuroblasts, but not in GFAP-positive astrocytes. In the OB, netrin-5
      expression was maintained in neuroblasts, but its level was decreased in NeuN
      positive mature neurons. In the hippocampal SGZ, netrin-5 was observed in Mash1
      positive cells and in DCX-positive neuroblasts, but not in GFAP-positive
      astrocytes, suggesting that netrin-5 expression occurs from type 2a to type 3
      cells. These data suggest that netrin-5 is produced by both transit-amplifying
      cells and neuroblasts to control neurogenesis in the adult brain. 

PMID- 25941473
TI  - Genotype-specific effects of Mecp2 loss-of-function on morphology of Layer V
      pyramidal neurons in heterozygous female Rett syndrome model mice.
AB  - Rett syndrome (RTT) is a progressive neurological disorder primarily caused by
      mutations in the X-linked gene methyl-CpG-binding protein 2 (MECP2). The
      heterozygous female brain consists of mosaic of neurons containing both wild-type
      MeCP2 (MeCP2+) and mutant MeCP2 (MeCP2-). Three-dimensional morphological
      analysis was performed on individually genotyped layer V pyramidal neurons in the
      primary motor cortex of heterozygous (Mecp2(+/-) ) and wild-type (Mecp2(+/+) )
      female mice ( > 6 mo.) from the Mecp2(tm1.1Jae) line. Comparing basal dendrite
      morphology, soma and nuclear size of MeCP2+ to MeCP2- neurons reveals a
      significant cell autonomous, genotype specific effect of Mecp2. MeCP2- neurons
      have 15% less total basal dendritic length, predominantly in the region 70-130
      MUm from the cell body and on average three fewer branch points, specifically
      loss in the second and third branch orders. Soma and nuclear areas of neurons of
      mice were analyzed across a range of ages (5-21 mo.) and X-chromosome
      inactivation (XCI) ratios (12-56%). On average, MeCP2- somata and nuclei were 15
      and 13% smaller than MeCP2+ neurons respectively. In most respects branching
      morphology of neurons in wild-type brains (MeCP2 WT) was not distinguishable from
      MeCP2+ but somata and nuclei of MeCP2 WT neurons were larger than those of MeCP2+
      neurons. These data reveal cell autonomous effects of Mecp2 mutation on dendritic
      morphology, but also suggest non-cell autonomous effects with respect to cell
      size. MeCP2+ and MeCP2- neuron sizes were not correlated with age, but were
      correlated with XCI ratio. Unexpectedly the MeCP2- neurons were smallest in
      brains where the XCI ratio was highly skewed toward MeCP2+, i.e., wild-type. This
      raises the possibility of cell non-autonomous effects that act through mechanisms
      other than globally secreted factors; perhaps competition for synaptic
      connections influences cell size and morphology in the genotypically mosaic brain
      of RTT model mice. 

PMID- 25941475
TI  - Reconciling the discrepancies on the involvement of large-conductance Ca(2+)
      activated K channels in glioblastoma cell migration.
AB  - Glioblastoma (GBM) is the most common and aggressive primary brain tumor, and is
      notable for spreading so effectively through the brain parenchyma to make
      complete surgical resection virtually impossible, and prospect of life dismal.
      Several ion channels have been involved in GBM migration and invasion, due to
      their critical role in supporting volume changes and Ca(2+) influx occuring
      during the process. The large-conductance, Ca(2+)-activated K (BK) channels,
      markedly overexpressed in biopsies of patients with GBMs and in GBM cell lines,
      have attracted much interest and have been suggested to play a central role in
      cell migration and invasion as candidate channels for providing the ion efflux
      and consequent water extrusion that allow cell shrinkage during migration.
      Available experimental data on the role of BK channel in migration and invasion
      are not consistent though. While BK channels block typically resulted in
      inhibition of cell migration or in no effect, their activation would either
      enhance or inhibit the process. This short review reexamines the relevant
      available data on the topic, and presents a unifying paradigm capable of
      reconciling present discrepancies. According to this paradigm, BK channels would
      not contribute to migration under conditions where the [Ca(2+)] i is too low for
      their activation. They will instead positively contribute to migration for
      intermediate [Ca(2+)] i , insufficient as such to activate BK channels, but
      capable of predisposing them to cyclic activation following oscillatory [Ca(2+)]
      i increases. Finally, steadily active BK channels because of prolonged high
      [Ca(2+)] i would inhibit migration as their steady activity would be unsuitable
      to match the cyclic cell volume changes needed for proper cell migration. 

PMID- 25941472
TI  - Molecular approaches for manipulating astrocytic signaling in vivo.
AB  - Astrocytes are the predominant glial type in the central nervous system and play
      important roles in assisting neuronal function and network activity. Astrocytes
      exhibit complex signaling systems that are essential for their normal function
      and the homeostasis of the neural network. Altered signaling in astrocytes is
      closely associated with neurological and psychiatric diseases, suggesting
      tremendous therapeutic potential of these cells. To further understand astrocyte
      function in health and disease, it is important to study astrocytic signaling in
      vivo. In this review, we discuss molecular tools that enable the selective
      manipulation of astrocytic signaling, including the tools to selectively activate
      and inactivate astrocyte signaling in vivo. Lastly, we highlight a few tools in
      development that present strong potential for advancing our understanding of the
      role of astrocytes in physiology, behavior, and pathology. 

PMID- 25941476
TI  - Molecular codes defining rostrocaudal domains in the embryonic mouse
      hypothalamus.
AB  - The prosomeric model proposes that the hypothalamus is a rostral forebrain
      entity, placed ventral to the telencephalon and rostral to the diencephalon. Gene
      expression markers differentially label molecularly distinct dorsoventral
      progenitor domains, which represent continuous longitudinal bands across the
      hypothalamic alar and basal regions. There is also circumstantial support for a
      rostrocaudal subdivision of the hypothalamus into transverse peduncular (caudal)
      and terminal (rostral) territories (PHy, THy). In addition, there is evidence for
      a specialized acroterminal domain at the rostral midline of the terminal
      hypothalamus (ATD). The PHy and THy transverse structural units are presently
      held to form part of two hypothalamo-telencephalic prosomeres (hp1 and hp2,
      respectively), which end dorsally at the telencephalic septocommissural roof. PHy
      and THy have distinct adult nuclei, at all dorsoventral levels. Here we report
      the results of data mining from the Allen Developing Mouse Brain Atlas database,
      looking for genes expressed differentially in the PHy, Thy, and ATD regions of
      the hypothalamus at several developmental stages. This search allowed us to
      identify additional molecular evidence supporting the postulated fundamental
      rostrocaudal bipartition of the mouse hypothalamus into the PHy and THy, and also
      corroborated molecularly the singularity of the ATD. A number of markers were
      expressed in Thy (Fgf15, Gsc, Nkx6.2, Otx1, Zic1/5), but were absent in PHy,
      while other genes showed the converse pattern (Erbb4, Irx1/3/5, Lmo4, Mfap4,
      Plagl1, Pmch). We also identified markers that selectively label the ATD
      (Fgf8/10/18, Otx2, Pomc, Rax, Six6). On the whole, these data help to explain
      why, irrespective of the observed continuity of all dorsoventral molecular
      hypothalamic subdivisions across PHy and THy, different nuclear structures
      originate within each of these two domains, and also why singular structures
      arise at the ATD, e.g., the suprachiasmatic nuclei, the arcuate nucleus, the
      median eminence and the neurohypophysis. 

PMID- 25941477
TI  - Rebuilding a realistic corticostriatal "social network" from dissociated cells.
AB  - Many of the methods available for the study of cortical influences on striatal
      neurons have serious problems. In vivo the connectivity is so complex that the
      study of input from an individual cortical neuron to a single striatal cell is
      nearly impossible. Mixed corticostriatal cultures develop many connections from
      striatal cells to cortical cells, in striking contrast to the fact that only
      connections from cortical cells to striatal cells are present in vivo.
      Furthermore, interneuron populations are over-represented in organotypic
      cultures. For these reasons, we have developed a method for growing cortical and
      striatal neurons in separated compartments that allows cortical neurons to
      innervate striatal cells in culture. The method works equally well for acutely
      dissociated or cryopreserved neurons and allows a number of manipulations that
      are not otherwise possible. Either cortical or striatal compartments can be
      transfected with channel rhodopsins. The activity of both areas can be recorded
      in multielectrode arrays or individual patch recordings from pairs of cells.
      Finally, corticostriatal connections can be severed acutely. This procedure
      enables determination of the importance of corticostriatal interaction in the
      resting pattern of activity. These cultures also facilitate development of
      sensitive analytical network methods to track connectivity. 

PMID- 25941478
TI  - Interaction effect between handedness and CNTNAP2 polymorphism (rs7794745
      genotype) on voice-specific frontotemporal activity in healthy individuals: an
      fMRI study.
AB  - Recent neuroimaging studies have demonstrated that Contactin-associated protein
      like2 (CNTNAP2) polymorphisms affect left-hemispheric function of language
      processing in healthy individuals, but no study has investigated the influence of
      these polymorphisms on right-hemispheric function involved in human voice
      perception. Further, although recent reports suggest that determination of
      handedness is influenced by genetic effect, the interaction effect between
      handedness and CNTNAP2 polymorphisms for brain activity in human voice perception
      and language processing has not been revealed. We aimed to investigate the
      interaction effect of handedness and CNTNAP2 polymorphisms in respect to brain
      function for human voice perception and language processing in healthy
      individuals. Brain function of 108 healthy volunteers (74 right-handed and 34 non
      right-handed) was examined while they were passively listening to reverse
      sentences (rSEN), identifiable non-vocal sounds (SND), and sentences (SEN). Full
      factorial design analysis was calculated by using three factors: (1) rs7794745
      (A/A or A/T), (2) rs2710102 [G/G or A carrier (A/G and A/A)], and (3) voice
      specific response (rSEN or SND). The main effect of rs7794745 (A/A or A/T) was
      significantly revealed at the right middle frontal gyrus (MFG) and bilateral
      superior temporal gyrus (STG). This result suggests that rs7794745 genotype
      affects voice-specific brain function. Furthermore, interaction effect was
      significantly observed among MFG-STG activations by human voice perception,
      rs7794745 (A/A or A/T), and handedness. These results suggest that CNTNAP2
      polymorphisms could be one of the important factors in the neural development
      related to vocal communication and language processing in both right-handed and
      non-right-handed healthy individuals. 

PMID- 25941479
TI  - Frontal midline theta oscillations during mental arithmetic: effects of stress.
AB  - Complex cognitive tasks such as mental arithmetic heavily rely on intact, well
      coordinated prefrontal cortex (PFC) function. Converging evidence suggests that
      frontal midline theta (FMT) oscillations play an important role during the
      execution of such PFC-dependent tasks. Additionally, it is well-established that
      acute stress impairs PFC function, and recent evidence suggests that FMT is
      decreased under stress. In this EEG study, we investigated FMT oscillations
      during a mental arithmetic task that was carried out in a stressful and a neutral
      control condition. Our results show late-onset, sustained FMT increases during
      mental arithmetic. In the neutral condition FMT started to increase earlier than
      in the stress condition. Direct comparison of the conditions quantified this
      difference by showing stronger FMT increases in the neutral condition in an early
      time window. Between-subject correlation analysis showed that attenuated FMT
      under stress was related to slowed reaction times. Our results suggest that FMT
      is associated with stimulus independent mental processes during the natural and
      complex PFC-dependent task of mental arithmetic, and is a possible marker for
      intact PFC function that is disrupted under stress. 

PMID- 25941480
TI  - Pain-related stress during the Neonatal Intensive Care Unit stay and SLC6A4
      methylation in very preterm infants.
AB  - Very preterm (VPT) infants need long-lasting hospitalization in the Neonatal
      Intensive Care Unit (NICU) during which they are daily exposed to pain-related
      stress. Alterations of DNA methylation at the promoter region of the SLC6A4 have
      been associated with early adverse experiences in infants. The main aim of the
      present work was to investigate the association between level of exposure to pain
      related stress during hospitalization and changes in SLC6A4 DNA methylation at
      NICU discharge in VPT infants. In order to exclude the potential effect of birth
      status (i.e., preterm vs. full-term birth) on SLC6A4 methylation, we
      preliminarily assessed SLC6A4 epigenetic differences between VPT and full-term
      (FT) infants at birth. Fifty-six VPT and thirty-two FT infants participated in
      the study. The level of exposure to pain-related stress was quantified on the
      basis of the amount of skin-breaking procedures to which they were exposed. VPT
      infants were divided in two sub-groups: low-pain exposure (LPE, N = 25) and high
      pain exposure (HPE, N = 31). DNA methylation was evaluated at birth for both VPT
      and FT infants, assessing 20 CpG sites within the SLC6A4 promoter region. The
      same CpG sites were re-evaluated for variations in DNA methylation at NICU
      discharge in LPE and HPE VPT infants. No differences in SLC6A4 CpG sites'
      methylation emerged between FT and VPT infants at birth. Methylation at CpG sites
      5 and 6 significantly increased from birth to NICU discharge only for HPE VPT
      infants. Findings show that preterm birth per se is not associated with
      epigenetic alterations of the SLC6A4, whereas higher levels of pain-related
      stress exposure during NICU stay might alter the transcriptional functionality of
      the serotonin transporter gene. 

PMID- 25941482
TI  - Corrigendum: Modeling habits as self-sustaining patterns of sensorimotor
      behavior.
AB  - [This corrects the article on p. 590 in vol. 8, PMID: 25152724.]. 

PMID- 25941481
TI  - Dual-task and electrophysiological markers of executive cognitive processing in
      older adult gait and fall-risk.
AB  - The role of cognition is becoming increasingly central to our understanding of
      the complexity of walking gait. In particular, higher-level executive functions
      are suggested to play a key role in gait and fall-risk, but the specific
      underlying neurocognitive processes remain unclear. Here, we report two
      experiments which investigated the cognitive and neural processes underlying
      older adult gait and falls. Experiment 1 employed a dual-task (DT) paradigm in
      young and older adults, to assess the relative effects of higher-level executive
      function tasks (n-Back, Serial Subtraction and visuo-spatial Clock task) in
      comparison to non-executive distracter tasks (motor response task and alphabet
      recitation) on gait. All DTs elicited changes in gait for both young and older
      adults, relative to baseline walking. Significantly greater DT costs were
      observed for the executive tasks in the older adult group. Experiment 2 compared
      normal walking gait, seated cognitive performances and concurrent event-related
      brain potentials (ERPs) in healthy young and older adults, to older adult
      fallers. No significant differences in cognitive performances were found between
      fallers and non-fallers. However, an initial late-positivity, considered a
      potential early P3a, was evident on the Stroop task for older non-fallers, which
      was notably absent in older fallers. We argue that executive control functions
      play a prominent role in walking and gait, but the use of neurocognitive
      processes as a predictor of fall-risk needs further investigation. 

PMID- 25941483
TI  - Behavior analysis and behavioral neuroscience.

PMID- 25941484
TI  - Developing synaesthesia: a primer.

PMID- 25941485
TI  - Parameter estimation of neuron models using in-vitro and in-vivo
      electrophysiological data.
AB  - Spiking neuron models can accurately predict the response of neurons to
      somatically injected currents if the model parameters are carefully tuned.
      Predicting the response of in-vivo neurons responding to natural stimuli presents
      a far more challenging modeling problem. In this study, an algorithm is presented
      for parameter estimation of spiking neuron models. The algorithm is a hybrid
      evolutionary algorithm which uses a spike train metric as a fitness function. We
      apply this to parameter discovery in modeling two experimental data sets with
      spiking neurons; in-vitro current injection responses from a regular spiking
      pyramidal neuron are modeled using spiking neurons and in-vivo extracellular
      auditory data is modeled using a two stage model consisting of a stimulus filter
      and spiking neuron model. 

PMID- 25941486
TI  - A critical review: coupling and synchronization analysis methods of EEG signal
      with mild cognitive impairment.
AB  - At present, the clinical diagnosis of mild cognitive impairment (MCI) patients
      becomes the important approach of evaluating early Alzheimer's disease. The
      methods of EEG signal coupling and synchronization act as a key role in
      evaluating and diagnosing MCI patients. Recently, these coupling and
      synchronization methods were used to analyze the EEG signals of MCI patients
      according to different angles, and many important discoveries have been achieved.
      However, considering that every method is single-faceted in solving problems,
      these methods have various deficiencies when analyzing EEG signals of MCI
      patients. This paper reviewed in detail the coupling and synchronization analysis
      methods, analyzed their advantages and disadvantages, and proposed a few research
      questions needed to solve in the future. Also, the principles and best
      performances of these methods were described. It is expected that the performance
      analysis of these methods can provide the theoretical basis for the method
      selection of analyzing EEG signals of MCI patients and the future research
      directions. 

PMID- 25941487
TI  - Therapeutic applications of circadian rhythms for the cardiovascular system.
AB  - The cardiovascular system exhibits dramatic time-of-day dependent rhythms, for
      example the diurnal variation of heart rate, blood pressure, and timing of onset
      of adverse cardiovascular events such as heart attack and sudden cardiac death.
      Over the past decade, the circadian clock mechanism has emerged as a crucial
      factor regulating these daily fluctuations. Most recently, these studies have led
      to a growing clinical appreciation that targeting circadian biology offers a
      novel therapeutic approach toward cardiovascular (and other) diseases. Here we
      describe leading-edge therapeutic applications of circadian biology including (1)
      timing of therapy to maximize efficacy in treating heart disease (chronotherapy);
      (2) novel biomarkers discovered by testing for genomic, proteomic, metabolomic,
      or other factors at different times of day and night (chronobiomarkers); and (3)
      novel pharmacologic compounds that target the circadian mechanism with potential
      clinical applications (new chronobiology drugs). Cardiovascular disease remains a
      leading cause of death worldwide and new approaches in the management and
      treatment of heart disease are clearly warranted and can benefit patients
      clinically. 

PMID- 25941488
TI  - Asymmetric author-topic model for knowledge discovering of big data in
      toxicogenomics.
AB  - The advancement of high-throughput screening technologies facilitates the
      generation of massive amount of biological data, a big data phenomena in
      biomedical science. Yet, researchers still heavily rely on keyword search and/or
      literature review to navigate the databases and analyses are often done in rather
      small-scale. As a result, the rich information of a database has not been fully
      utilized, particularly for the information embedded in the interactive nature
      between data points that are largely ignored and buried. For the past 10 years,
      probabilistic topic modeling has been recognized as an effective machine learning
      algorithm to annotate the hidden thematic structure of massive collection of
      documents. The analogy between text corpus and large-scale genomic data enables
      the application of text mining tools, like probabilistic topic models, to explore
      hidden patterns of genomic data and to the extension of altered biological
      functions. In this paper, we developed a generalized probabilistic topic model to
      analyze a toxicogenomics dataset that consists of a large number of gene
      expression data from the rat livers treated with drugs in multiple dose and time
      points. We discovered the hidden patterns in gene expression associated with the
      effect of doses and time-points of treatment. Finally, we illustrated the ability
      of our model to identify the evidence of potential reduction of animal use. 

PMID- 25941489
TI  - Stabilization of G protein-coupled receptors by point mutations.
AB  - G protein-coupled receptors (GPCRs) are flexible integral membrane proteins
      involved in transmembrane signaling. Their involvement in many physiological
      processes makes them interesting targets for drug development. Determination of
      the structure of these receptors will help to design more specific drugs,
      however, their structural characterization has so far been hampered by the low
      expression and their inherent instability in detergents which made protein
      engineering indispensable for structural and biophysical characterization.
      Several approaches to stabilize the receptors in a particular conformation have
      led to breakthroughs in GPCR structure determination. These include truncations
      of the flexible regions, stabilization by antibodies and nanobodies, fusion
      partners, high affinity and covalently bound ligands as well as conformational
      stabilization by mutagenesis. In this review we focus on stabilization of GPCRs
      by insertion of point mutations, which lead to increased conformational and
      thermal stability as well as improved expression levels. We summarize existing
      mutagenesis strategies with different coverage of GPCR sequence space and depth
      of information, design and transferability of mutations and the molecular basis
      for stabilization. We also discuss whether mutations alter the structure and
      pharmacological properties of GPCRs. 

PMID- 25941491
TI  - Altered beta1-3-adrenoceptor influence on alpha2-adrenoceptor-mediated control of
      catecholamine release and vascular tension in hypertensive rats.
AB  - alpha2- and beta-adrenoceptors (AR) reciprocally control catecholamine release
      and vascular tension. Disorders in these functions are present in spontaneously
      hypertensive rats (SHR). The present study tested if alpha2AR dysfunctions
      resulted from altered alpha2AR/betaAR interaction. Blood pressure (BP) was
      recorded through a femoral artery catheter and cardiac output by an ascending
      aorta flow probe. Total peripheral vascular resistance (TPR) was calculated.
      Norepinephrine release was stimulated by a 15-min tyramine-infusion, which allows
      presynaptic release-control to be reflected as differences in overflow to plasma.
      Surgical stress activated some secretion of epinephrine. L-659,066 (alpha2AR
      antagonist) enhanced norepinephrine overflow in normotensive controls (WKY) but
      not SHR. Nadolol (beta1+2) and ICI-118551 (beta2), but not atenolol (beta1) or
      SR59230A [beta(3)/1L ] prevented this increase. All betaAR antagonists allowed L
      659,066 to augment tyramine-induced norepinephrine overflow in SHR and
      epinephrine secretion in both strains. Inhibition of cAMP-degradation with
      milrinone and beta3AR agonist (BRL37344) enhanced the effect of L-659,066 on
      release of both catecholamines in SHR and epinephrine in WKY. beta1/2AR
      antagonists and BRL37344 opposed the L-659,066-dependent elimination of the TPR
      response to tyramine in WKY. alpha2AR/betaAR antagonists had little influence on
      the TPR-response in SHR. Milrinone potentiated the L-659,066-dependent reduction
      of the TPR-response to tyramine. CONCLUSIONS: beta2AR activity was a required
      substrate for alpha2AR auto inhibition of norepinephrine release in WKY.
      beta1+2AR opposed alpha2AR inhibition of norepinephrine release in SHR and
      epinephrine secretion in both strains. betaAR-alpha2AR reciprocal control of
      vascular tension was absent in SHR. Selective agonist provoked beta3AR-Gi
      signaling and influenced the tyramine-induced TPR-response in WKY and
      catecholamine release in SHR.

PMID- 25941492
TI  - Chronic sustained hypoxia-induced redox remodeling causes contractile dysfunction
      in mouse sternohyoid muscle.
AB  - Chronic sustained hypoxia (CH) induces structural and functional adaptations in
      respiratory muscles of animal models, however the underlying molecular mechanisms
      are unclear. This study explores the putative role of CH-induced redox remodeling
      in a translational mouse model, with a focus on the sternohyoid-a representative
      upper airway dilator muscle involved in the control of pharyngeal airway caliber.
      We hypothesized that exposure to CH induces redox disturbance in mouse
      sternohyoid muscle in a time-dependent manner affecting metabolic capacity and
      contractile performance. C57Bl6/J mice were exposed to normoxia or normobaric CH
      (FiO2 = 0.1) for 1, 3, or 6 weeks. A second cohort of animals was exposed to CH
      for 6 weeks with and without antioxidant supplementation (tempol or N-acetyl
      cysteine in the drinking water). Following CH exposure, we performed 2D redox
      proteomics with mass spectrometry, metabolic enzyme activity assays, and cell
      signaling assays. Additionally, we assessed isotonic contractile and endurance
      properties ex vivo. Temporal changes in protein oxidation and glycolytic enzyme
      activities were observed. Redox modulation of sternohyoid muscle proteins key to
      contraction, metabolism and cellular homeostasis was identified. There was no
      change in redox-sensitive proteasome activity or HIF-1alpha content, but CH
      decreased phospho-JNK content independent of antioxidant supplementation. CH was
      detrimental to sternohyoid force- and power-generating capacity and this was
      prevented by chronic antioxidant supplementation. We conclude that CH causes
      upper airway dilator muscle dysfunction due to redox modulation of proteins key
      to function and homeostasis. Such changes could serve to further disrupt
      respiratory homeostasis in diseases characterized by CH such as chronic
      obstructive pulmonary disease. Antioxidants may have potential use as an
      adjunctive therapy in hypoxic respiratory disease. 

PMID- 25941493
TI  - A New Tool for in vivo Manipulation of Brain microRNA Levels: The Work of
      Smalheiser et al. (2014).

PMID- 25941490
TI  - Extracellular hemoglobin: the case of a friend turned foe.
AB  - Hemoglobin (Hb) is a highly conserved molecule present in all life forms and
      functionally tied to the complexity of aerobic organisms on earth in utilizing
      oxygen from the atmosphere and delivering to cells and tissues. This primary
      function sustains the energy requirements of cells and maintains cellular
      homeostasis. Decades of intensive research has presented a paradigm shift that
      shows how the molecule also functions to facilitate smooth oxygen delivery
      through the cardiovascular system for cellular bioenergetic homeostasis and
      signaling for cell function and defense. These roles are particularly highlighted
      in the binding of Hb to gaseous molecules carbon dioxide (CO2), nitric oxide (NO)
      and carbon monoxide (CO), while also serving indirectly or directly as sources of
      these signaling molecules. The functional activities impacted by Hb outside of
      bioenergetics homeostasis, include fertilization, signaling functions, modulation
      of inflammatory responses for defense and cell viability. These activities are
      efficiently executed while Hb is sequestered safely within the confines of the
      red blood cell (rbc). Outside of rbc confines, Hb disaggregates and becomes a
      danger molecule to cell survival. In these perpectives, Hb function is broadly
      dichotomous, either a friend in its natural environment providing and
      facilitating the means for cell function or foe when dislocated from its habitat
      under stress or pathological condition disrupting cell function. The review
      presents insights into how this dichotomy in function manifests. 

PMID- 25941494
TI  - Attention-deficit/hyperactivity disorder in relation to addictive behaviors: a
      moderated-mediation analysis of personality-risk factors and sex.
AB  - INTRODUCTION: Research has shown that those with attention-deficit/hyperactivity
      disorder (ADHD) have an increased risk for addiction disorders like alcoholism
      and substance abuse. What is less clear is the mechanism(s) whereby ADHD gives
      rise to increased engagement in addictive behaviors, and whether there are sex
      differences in the ADHD-addiction propensity. Both ADHD and addictions have also
      been associated with personality traits such as impulsivity, reward seeking,
      anxiousness, and negative affect. In this study, we tested a moderator-mediation
      model, which predicted that both sex and ADHD-symptom status would make
      independent contributions to the variance in personality risk and in addictive
      behaviors, with males, and those with diagnosed ADHD, scoring higher on both
      dependent variables. Our model also predicted that the effect of sex and ADHD
      symptom status on addictive behaviors would be via the mediating or intervening
      influence of personality-risk factors. METHODS: A community-based sample of young
      men and women took part in the study. Among these individuals, 46 had received a
      lifetime diagnosis of ADHD. The non-diagnosed participants were dichotomized into
      a high-ADHD-symptom group (n = 83) and a low-symptom group (n = 84). RESULTS: We
      found that a high-risk personality profile may, in part, account for the
      relationship between ADHD symptomatology and the use/abuse of a broad range of
      addictive behaviors. However, we found no sex differences in personality risk for
      addiction or in the use of addictive behaviors; nor did sex moderate the
      relationships we assessed. CONCLUSION: While ADHD status showed a strong
      relationship with both dependent variables in the model, we found no difference
      between those who had been diagnosed with ADHD and treated with stimulants, and
      their high-symptom non-diagnosed/non-treated counterparts. These results add
      support to claims that the treatment of ADHD with stimulant medication neither
      protects nor fosters the risk for substance abuse disorders.

PMID- 25941496
TI  - Factors Predicting Cybersex Use and Difficulties in Forming Intimate
      Relationships among Male and Female Users of Cybersex.
AB  - Sexual addiction otherwise known as compulsive sexual behavior is associated with
      serious psychosocial problems and risk-taking behavior. This study used the
      Cybersex addiction test, Craving for pornography questionnaire, and a
      Questionnaire on intimacy among 267 participants (192 males and 75 females) mean
      age for males 28.16 (SD = 6.8) and for females 25.5 (SD = 5.13) who were
      recruited from special sites that are dedicated to pornography and cybersex on
      the Internet. Results of regression analysis indicated that pornography, gender,
      and cybersex significantly predicted difficulties in intimacy and it accounted
      for 66.1% of the variance of rating on the intimacy questionnaire. Second,
      regression analysis also indicated that craving for pornography, gender, and
      difficulties in forming intimate relationships significantly predicted frequency
      of cybersex use and it accounted for 83.7% of the variance in ratings of cybersex
      use. Third, men had higher scores of frequency of using cybersex than women
      [t(2,224) = 1.97, p < 0.05] and higher scores of craving for pornography than
      women [t(2,265) = 3.26, p < 0.01] and no higher scores on the questionnaire
      measuring difficulties in forming intimate relationship than women [t(2,224) = 1,
      p = 0.32]. These findings support previous evidence for sex differences in
      compulsive sexual behavior. 

PMID- 25941497
TI  - Response of depression to botulinum toxin treatment: agitation as a predictor.

PMID- 25941495
TI  - Judging Strangers' Trustworthiness is Associated with Theory of Mind Skills.
AB  - Trusting people requires evaluating them to assess their trustworthiness.
      Evaluating a stranger's intentions is likely to be one method of assessing
      trustworthiness. The present study tested the hypothesis that judgments of
      trustworthiness are associated with mind reading skills, also called theory of
      mind (ToM). We tested a group of healthy participants and a group of patients
      with paranoid schizophrenia. Both groups made ToM judgments and judged the
      trustworthiness of strangers. Participants were also assessed for their
      disposition to trust as well as levels of paranoid belief. As anticipated,
      healthy participants had a normal ToM scores and patients with paranoid
      schizophrenia had poor ToM scores. In paranoid patients, better ability to read
      others' minds was associated with judging others as more trustworthy, while the
      reverse was found in the healthy participants (better mind reading was associated
      with judging others as less trustworthy), suggesting a non-linear relationship
      between trust in others and being able to read their intentions. 

PMID- 25941498
TI  - Sex-dependent vulnerability to cannabis abuse in adolescence.
AB  - The goal of this review is to summarize current evidence for sex differences in
      the response to cannabinoid compounds, focusing mainly on a specific age of
      exposure, i.e., adolescence. Preclinical as well as clinical studies are
      examined. Among the different possible underlying mechanisms, the consistent
      dimorphism in the endocannabinoid system and delta9-tetrahydrocannabinol
      metabolism may play a part. All the collected data point to the need of including
      females in basic research as well as of analyzing results for sex differences in
      epidemiological studies. 

PMID- 25941499
TI  - Improvisation and the self-organization of multiple musical bodies.
AB  - Understanding everyday behavior relies heavily upon understanding our ability to
      improvise, how we are able to continuously anticipate and adapt in order to
      coordinate with our environment and others. Here we consider the ability of
      musicians to improvise, where they must spontaneously coordinate their actions
      with co-performers in order to produce novel musical expressions. Investigations
      of this behavior have traditionally focused on describing the organization of
      cognitive structures. The focus, here, however, is on the ability of the time
      evolving patterns of inter-musician movement coordination as revealed by the
      mathematical tools of complex dynamical systems to provide a new understanding of
      what potentiates the novelty of spontaneous musical action. We demonstrate this
      approach through the application of cross wavelet spectral analysis, which
      isolates the strength and patterning of the behavioral coordination that occurs
      between improvising musicians across a range of nested time-scales. Revealing the
      sophistication of the previously unexplored dynamics of movement coordination
      between improvising musicians is an important step toward understanding how
      creative musical expressions emerge from the spontaneous coordination of multiple
      musical bodies. 

PMID- 25941500
TI  - Mojibake - The rehearsal of word fragments in verbal recall.
AB  - Theories of verbal rehearsal usually assume that whole words are being rehearsed.
      However, words consist of letter sequences, or syllables, or word onset-vowel
      coda, amongst many other conceptualizations of word structure. A more general
      term is the 'grain size' of word units (Ziegler and Goswami, 2005). In the
      current study, a new method measured the quantitative percentage of correctly
      remembered word structure. The amount of letters in the correct letter sequence
      as per cent of word length was calculated, disregarding missing or added letters.
      A forced rehearsal was tested by repeating each memory list four times. We tested
      low frequency (LF) English words versus geographical (UK) town names to control
      for content. We also tested unfamiliar international (INT) non-words and names of
      international (INT) European towns to control for familiarity. An immediate
      versus distributed repetition was tested with a between-subject design.
      Participants responded with word fragments in their written recall especially
      when they had to remember unfamiliar words. While memory of whole words was
      sensitive to content, presentation distribution and individual sex and language
      differences, recall of word fragments was not. There was no trade-off between
      memory of word fragments with whole word recall during the repetition, instead
      also word fragments significantly increased. Moreover, while whole word responses
      correlated with each other during repetition, and word fragment responses
      correlated with each other during repetition, these two types of word recall
      responses were not correlated with each other. Thus there may be a lower layer
      consisting of free, sparse word fragments and an upper layer that consists of
      language-specific, orthographically and semantically constrained words. 

PMID- 25941501
TI  - Intranasal adminsitration of oxytocin in postnatal depression: implications for
      psychodynamic psychotherapy from a randomized double-blind pilot study.
AB  - Oxytocin is a neuropeptide that is active in the central nervous system and is
      generally considered to be involved in prosocial behaviors and feelings. In light
      of its documented positive effect on maternal behavior, we designed a study to
      ascertain whether oxytocin exerts any therapeutic effects on depressive symptoms
      in women affected by maternal postnatal depression. A group of 16 mothers were
      recruited in a randomized double-blind study: the women agreed to take part in a
      brief course of psychoanalytic psychotherapy (12 sessions, once a week) while
      also being administered, during the 12-weeks period, a daily dose of intranasal
      oxytocin (or a placebo). The pre-treatment evaluation also included a personality
      assessment of the major primary-process emotional command systems described by
      Panksepp () and a semi-quantitative assessment by the therapist of the mother's
      depressive symptoms and of her personality. No significant effect on depressive
      symptomatology was found following the administration of oxytocin (as compared to
      a placebo) during the period of psychotherapy. Nevertheless, a personality trait
      evaluation of the mothers, conducted in our overall sample group, showed a
      decrease in the narcissistic trait only within the group who took oxytocin. The
      depressive (dysphoric) trait was in fact significantly affected by psychotherapy
      (this effect was only present in the placebo group so it may reflect a positive
      placebo effect enhancing the favorable influence of psychotherapy on depressive
      symptoms) but not in the presence of oxytocin. Therefore, the neuropeptide would
      appear to play some role in the modulation of cerebral functions involved in the
      self-centered (narcissistic) dimension of the suffering that can occur with
      postnatal depression. Based on these results, there was support for our
      hypothesis that what is generally defined as postnatal depression may include
      disturbances of narcissistic affective balance, and oxytocin supplementation can
      counteract that type of affective disturbance. The resulting improvements in well
      being, reflected in better self-centering in post-partuent mothers, may in turn
      facilitate better interpersonal acceptance of (and interactions with) the child
      and thereby, improved recognition of the child's needs. 

PMID- 25941502
TI  - If so many are "few," how few are "many"?
AB  - The scope of reference of a word's meaning can be highly variable. We present a
      novel paradigm to investigate the flexible interpretation of word meaning. We
      focus on quantifiers such as "many" or "few," a class of words that depends on
      number knowledge but can be interpreted in a flexible manner. Healthy young
      adults performed a truth value judgment task on pictorial arrays of varying
      amounts of blue and yellow circles, deciding whether the sentence "Many/few of
      the circles are yellow" was an adequate description of the stimulus. The study
      consisted of two experiments, one focusing on "many," one on "few." Each
      experiment had three blocks. In a first "baseline" block, each individual's
      criterion for "many" and "few" was assessed. In a second "adaptation" block,
      subjects received feedback about their decisions that was different from their
      initial judgments in an effort to evaluate the flexibility of a subject's
      interpretation. A third "test" block assessed whether adaptation of quantifier
      meaning induced in block 2 then was generalized to alter a subject's baseline
      meaning for "many" and "few." In Experiment 1, a proportion of yellow circles as
      small as 40% was reinforced as "many"; in Experiment 2, a proportion of yellow
      circles as large as 60% was reinforced as "few." Subjects learned the new
      criterion for "many" in Experiment 1, which also affected their criterion for
      "few" although it had never been mentioned. Likewise, in Experiment 2, subjects
      changed their criterion for "few," with a comparable effect on the criterion for
      "many" which was not mentioned. Thus, the meaning of relational quantifiers like
      "many" and "few" is flexible and can be adapted. Most importantly, adapting the
      criterion for one quantifier (e.g., "many") also appeared to affect the
      reciprocal quantifier (in this case, "few"). Implications of this result for
      psychological interventions and for investigations of the neurobiology of the
      language-number interface are discussed. 

PMID- 25941503
TI  - Phonology is not accessed earlier than orthography in Chinese written production:
      evidence for the orthography autonomy hypothesis.
AB  - The contribution of orthographic and phonological codes to written production
      remains controversial. We report results using a picture-word interference task
      in which participants were asked to write (Experiments 1 and 2) or to speak
      (Experiment 3) the names of pictures while trying to ignore visual distractors,
      and the interval between the target and distractor onset was varied. Distractors
      were orthographically plus phonologically related, orthographically related,
      phonologically related, or unrelated to picture names. For written production, we
      found an exclusive orthographic effect at an early stage, reflecting a fast and
      direct link between meaning and graphemic lexicon, and we demonstrated that
      orthographic codes can be accessed directly from meaning in healthy adults. We
      also found orthographic and phonological effects at a later stage, reflecting a
      slow and indirect link between meaning and graphemic lexicon via phonology.
      Furthermore, the absence of an interaction effect of orthographic and
      phonological facilitation on written latencies suggests that the two effects are
      additive in general and that they might occur independently in written production
      in Chinese. For spoken production, we found that orthographic and phonological
      effects occur simultaneously in spoken production and that the two effects are
      additive at an early stage but interactive at a later stage. The temporal courses
      and their interplay of orthographic and phonological effects are dissociative in
      written and spoken production. Our findings thus support the orthography autonomy
      hypothesis, rather than the obligatory phonological mediation hypothesis, in
      written production in Chinese (as a non-alphabetic script). 

PMID- 25941504
TI  - Gaze cuing of attention in snake phobic women: the influence of facial
      expression.
AB  - Only a few studies investigated whether animal phobics exhibit attentional biases
      in contexts where no phobic stimuli are present. Among these, recent studies
      provided evidence for a bias toward facial expressions of fear and disgust in
      animal phobics. Such findings may be due to the fact that these expressions could
      signal the presence of a phobic object in the surroundings. To test this
      hypothesis and further investigate attentional biases for emotional faces in
      animal phobics, we conducted an experiment using a gaze-cuing paradigm in which
      participants' attention was driven by the task-irrelevant gaze of a centrally
      presented face. We employed dynamic negative facial expressions of disgust, fear
      and anger and found an enhanced gaze-cuing effect in snake phobics as compared to
      controls, irrespective of facial expression. These results provide evidence of a
      general hypervigilance in animal phobics in the absence of phobic stimuli, and
      indicate that research on specific phobias should not be limited to symptom
      provocation paradigms. 

PMID- 25941505
TI  - Sounding Black or White: priming identity and biracial speech.
AB  - Research has shown that priming one's racial identity can alter a biracial
      individuals' social behavior, but can such priming also influence their speech?
      Language is often used as a marker of one's social group membership and studies
      have shown that social context can affect the style of language that a person
      chooses to use, but this work has yet to be extended to the biracial population.
      Audio clips were extracted from a previous study involving biracial Black/White
      participants who had either their Black or White racial identity primed.
      Condition-blind coders rated Black-primed biracial participants as sounding
      significantly more Black and White-primed biracial participants as sounding
      significantly more White, both when listening to whole (Study 1a) and thin-sliced
      (Study 1b) clips. Further linguistic analyses (Studies 2a-c) were inconclusive
      regarding the features that differed between the two groups. Future directions
      regarding the need to investigate the intersections between social identity
      priming and language behavior with a biracial lens are discussed. 

PMID- 25941506
TI  - Multisensory and sensorimotor interactions in speech perception.

PMID- 25941507
TI  - Spelling impairments in Spanish dyslexic adults.
AB  - Spelling deficits have repeatedly been observed in children with dyslexia.
      However, the few studies addressing this issue in dyslexic adults have reported
      contradictory results. We investigated whether Spanish dyslexics show spelling
      deficits in adulthood and which components of the writing production process
      might be impaired in developmental dyslexia. In order to evaluate the involvement
      of the lexical and the sublexical routes of spelling as well as the graphemic
      buffer, lexical frequency, phonology-to-orthography consistency and word length
      were manipulated in two writing tasks: a direct copy transcoding task and a
      spelling-to-dictation task. Results revealed that adults with dyslexia produced
      longer written latencies, inter-letter intervals, writing durations and more
      errors than their peers without dyslexia. Moreover, the dyslexics were more
      affected by lexical frequency and word length than the controls, but both groups
      showed a similar effect of P-O consistency. Written latencies also revealed that
      while the dyslexics initiated the response later in the direct copy transcoding
      task than in the spelling-to-dictation task, the controls showed the opposite
      pattern. However, the dyslexics were slower than the controls in both tasks.
      Results were consistent with the hypothesis that spelling difficulties are
      present in adults with dyslexia, at least in a language with a transparent
      orthography such as Spanish. These difficulties seem to be associated with a
      deficit affecting both lexical processing and the ability to maintain information
      about the serial order of the letters in a word. However, the dyslexic group did
      not differ from the control group in the application of the P-O conversion
      procedures. The spelling impairment would be in addition to the reading deficit,
      leading to poorer performance in direct copy transcoding compared to spelling-to
      dictation. 

PMID- 25941508
TI  - Myopic decisions under negative emotions correlate with altered time perception.
AB  - Previous studies have obtained inconsistent findings about emotional influence on
      inter-temporal choice (IC). In the present study, we first examined the effect of
      temporary emotional priming induced by affective pictures in a trial-to-trial
      paradigm on IC. The results showed that negative priming resulted in much higher
      percentages of trials during which smaller-but-sooner reward (SS%) were chosen
      compared with positive and neutral priming. Next, we attempted to explore the
      possible mechanisms underlying such emotional effects. When participants
      performed a time reproduction task, mean reaction times in negative priming
      condition were significantly shorter than those in the other two emotional
      contexts, which indicated that negative emotional priming led to overestimation
      of time. Moreover, such overestimation was negatively correlated with performance
      in the IC task. In contrast, temporary changes of emotional contexts did not
      alter performances in a Go/NoGo task (including commission errors and omission
      errors). In sum, our present findings suggested that myopic decisions under
      negative emotions were associated with altered time perception but not response
      inhibition. 

PMID- 25941509
TI  - Vection and visually induced motion sickness: how are they related?
AB  - The occurrence of visually induced motion sickness has been frequently linked to
      the sensation of illusory self-motion (vection), however, the precise nature of
      this relationship is still not fully understood. To date, it is still a matter of
      debate as to whether vection is a necessary prerequisite for visually induced
      motion sickness (VIMS). That is, can there be VIMS without any sensation of self
      motion? In this paper, we will describe the possible nature of this relationship,
      review the literature that addresses this relationship (including theoretical
      accounts of vection and VIMS), and offer suggestions with respect to
      operationally defining and reporting these phenomena in future. 

PMID- 25941510
TI  - Schizophrenia: from neurophysiological abnormalities to clinical symptoms.

PMID- 25941511
TI  - Psychostimulants and movement disorders.
AB  - Psychostimulants are a diverse group of substances with their main psychomotor
      effects resembling those of amphetamine, methamphetamine, cocaine, or cathinone.
      Due to their potential as drugs of abuse, recreational use of most of these
      substances is illegal since 1971 Convention on Psychotropic Substances. In recent
      years, new psychoactive substances have emerged mainly as synthetic cathinones
      with new molecules frequently complementing the list. Psychostimulant related
      movement disorders are a known entity often seen in emergency rooms around the
      world. These admissions are becoming more frequent as are fatalities associated
      with drug abuse. Still the legal constraints of the novel synthetic molecules are
      bypassed. At the same time, chronic and permanent movement disorders are much
      less frequently encountered. These disorders frequently manifest as a combination
      of movement disorders. The more common symptoms include agitation, tremor,
      hyperkinetic and stereotypical movements, cognitive impairment, and also
      hyperthermia and cardiovascular dysfunction. The pathophysiological mechanisms
      behind the clinical manifestations have been researched for decades. The common
      denominator is the monoaminergic signaling. Dopamine has received the most
      attention but further research has demonstrated involvement of other pathways.
      Common mechanisms linking psychostimulant use and several movement disorders
      exist. 

PMID- 25941513
TI  - Cell-to-cell communication in bilateral macronodular adrenal hyperplasia causing
      hypercortisolism.
AB  - It has been well established that, in the human adrenal gland, cortisol secretion
      is not only controlled by circulating corticotropin but is also influenced by a
      wide variety of bioactive signals, including conventional neurotransmitters and
      neuropeptides, released within the cortex by various cell types such as
      chromaffin cells, neurons, cells of the immune system, adipocytes, and
      endothelial cells. These different types of cells are present in bilateral
      macronodular adrenal hyperplasia (BMAH), a rare etiology of primary adrenal
      Cushing's syndrome, where they appear intermingled with adrenocortical cells in
      the hyperplastic cortex. In addition, the genetic events, which cause the
      disease, favor abnormal adrenal differentiation that results in illicit
      expression of paracrine regulatory factors and their receptors in adrenocortical
      cells. All these defects constitute the molecular basis for aberrant
      autocrine/paracrine regulatory mechanisms, which are likely to play a role in the
      pathophysiology of BMAH-associated hypercortisolism. The present review
      summarizes the current knowledge on this topic as well as the therapeutic
      perspectives offered by this new pathophysiological concept. 

PMID- 25941514
TI  - Diel metabolomics analysis of a hot spring chlorophototrophic microbial mat leads
      to new hypotheses of community member metabolisms.
AB  - Dynamic environmental factors such as light, nutrients, salt, and temperature
      continuously affect chlorophototrophic microbial mats, requiring adaptive and
      acclimative responses to stabilize composition and function. Quantitative
      metabolomics analysis can provide insights into metabolite dynamics for
      understanding community response to such changing environmental conditions. In
      this study, we quantified volatile organic acids, polar metabolites (amino acids,
      glycolytic and citric acid cycle intermediates, nucleobases, nucleosides, and
      sugars), wax esters, and polyhydroxyalkanoates, resulting in the identification
      of 104 metabolites and related molecules in thermal chlorophototrophic microbial
      mat cores collected over a diel cycle in Mushroom Spring, Yellowstone National
      Park. A limited number of predominant taxa inhabit this community and their
      functional potentials have been previously identified through metagenomic and
      metatranscriptomic analyses and in situ metabolisms, and metabolic interactions
      among these taxa have been hypothesized. Our metabolomics results confirmed the
      diel cycling of photorespiration (e.g., glycolate) and fermentation (e.g.,
      acetate, propionate, and lactate) products, the carbon storage polymers
      polyhydroxyalkanoates, and dissolved gasses (e.g., H2 and CO2) in the waters
      overlying the mat, which were hypothesized to occur in major mat
      chlorophototrophic community members. In addition, we have formulated the
      following new hypotheses: (1) the morning hours are a time of biosynthesis of
      amino acids, DNA, and RNA; (2) photo-inhibited cells may also produce lactate via
      fermentation as an alternate metabolism; (3) glycolate and lactate are exchanged
      among Synechococcus and Roseiflexus spp.; and (4) fluctuations in many metabolite
      pools (e.g., wax esters) at different times of day result from species found at
      different depths within the mat responding to temporal differences in their
      niches. 

PMID- 25941515
TI  - pH levels drive bacterial community structure in sediments of the Qiantang River
      as determined by 454 pyrosequencing.
AB  - The Qiantang River is a typical freshwater ecosystem that acts as an
      irreplaceable water source in Zhejiang Province in southeastern China. However,
      the effects of environmental factors on the bacterial community of this
      freshwater ecosystem have not been determined. In this study, seven sediment
      samples were collected along the river. Their bacterial communities were
      identified using 454 high-throughput sequencing, and the primary environmental
      factors responsible for shaping the community structure were analyzed. The number
      of bacterial operational taxonomic units (OTUs) ranged from 2637 to 3933. Using a
      linear-regression analysis, the OTU numbers were significantly positively
      correlated with pH (r = 0.832, p < 0.05) and negatively correlated with nitrate
      concentration (r = -0.805, p < 0.05). A redundancy analysis (RDA) was also
      performed to test the relationship between the environmental factors and
      bacterial community composition. The results indicated that pH (p < 0.05) and
      nitrate concentration (p < 0.05) were the most significant factors that
      determined the community distribution of sediment bacteria. 

PMID- 25941512
TI  - Circadian Clock Dysfunction and Psychiatric Disease: Could Fruit Flies have a
      Say?
AB  - There is evidence of a link between the circadian system and psychiatric
      diseases. Studies in humans and mammals suggest that environmental and/or genetic
      disruption of the circadian system leads to an increased liability to psychiatric
      disease. Disruption of clock genes and/or the clock network might be related to
      the etiology of these pathologies; also, some genes, known for their circadian
      clock functions, might be associated to mental illnesses through clock
      independent pleiotropy. Here, we examine the features which we believe make
      Drosophila melanogaster a model apt to study the role of the circadian clock in
      psychiatric disease. Despite differences in the organization of the clock system,
      the molecular architecture of the Drosophila and mammalian circadian oscillators
      are comparable and many components are evolutionarily related. In addition,
      Drosophila has a rather complex nervous system, which shares much at the cell and
      neurobiological level with humans, i.e., a tripartite brain, the main
      neurotransmitter systems, and behavioral traits: circadian behavior, learning and
      memory, motivation, addiction, social behavior. There is evidence that the
      Drosophila brain shares some homologies with the vertebrate cerebellum, basal
      ganglia, and hypothalamus-pituitary-adrenal axis, the dysfunctions of which have
      been tied to mental illness. We discuss Drosophila in comparison to mammals with
      reference to the: organization of the brain and neurotransmitter systems;
      architecture of the circadian clock; clock-controlled behaviors. We sum up
      current knowledge on behavioral endophenotypes, which are amenable to modeling in
      flies, such as defects involving sleep, cognition, or social interactions, and
      discuss the relationship of the circadian system to these traits. Finally, we
      consider if Drosophila could be a valuable asset to understand the relationship
      between circadian clock malfunction and psychiatric disease. 

PMID- 25941516
TI  - The anionic biosurfactant rhamnolipid does not denature industrial enzymes.
AB  - Biosurfactants (BS) are surface-active molecules produced by microorganisms.
      Their combination of useful properties and sustainable production make them
      promising industrial alternatives to petrochemical and oleochemical surfactants.
      Here we compare the impact of the anionic BS rhamnolipid (RL) and the
      conventional/synthetic anionic surfactant sodium dodecyl sulfate (SDS) on the
      structure and stability of three different commercially used enzymes, namely the
      cellulase Carezyme(r) (CZ), the phospholipase Lecitase Ultra(r) (LT) and the
      alpha-amylase Stainzyme(r) (SZ). Our data reveal a fundamental difference in
      their mode of interaction. SDS shows great diversity of interaction toward the
      different enzymes. It efficiently unfolds both LT and CZ, but LT is unfolded by
      SDS through formation of SDS clusters on the enzyme well below the cmc, while CZ
      is only unfolded by bulk micelles and on average binds significantly less SDS
      than LT. SDS binds with even lower stoichiometry to SZ and leads to an increase
      in thermal stability. In contrast, RL does not affect the tertiary or secondary
      structure of any enzyme at room temperature, has little impact on thermal
      stability and only binds detectably (but at low stoichiometries) to SZ.
      Furthermore, all enzymes maintain activity at both monomeric and micellar
      concentrations of RL. We conclude that RL, despite its anionic charge, is a
      surfactant that does not compromise the structural integrity of industrially
      relevant enzymes. This makes RL a promising alternative to current synthetic
      anionic surfactants in a wide range of commercial applications. 

PMID- 25941518
TI  - Microbial diversity on Icelandic glaciers and ice caps.
AB  - Algae are important primary colonizers of snow and glacial ice, but hitherto
      little is known about their ecology on Iceland's glaciers and ice caps. Due do
      the close proximity of active volcanoes delivering large amounts of ash and dust,
      they are special ecosystems. This study provides the first investigation of the
      presence and diversity of microbial communities on all major Icelandic glaciers
      and ice caps over a 3 year period. Using high-throughput sequencing of the small
      subunit ribosomal RNA genes (16S and 18S), we assessed the snow community
      structure and complemented these analyses with a comprehensive suite of physical
      , geo-, and biochemical characterizations of the aqueous and solid components
      contained in snow and ice samples. Our data reveal that a limited number of snow
      algal taxa (Chloromonas polyptera, Raphidonema sempervirens and two uncultured
      Chlamydomonadaceae) support a rich community comprising of other micro
      eukaryotes, bacteria and archaea. Proteobacteria and Bacteroidetes were the
      dominant bacterial phyla. Archaea were also detected in sites where snow algae
      dominated and they mainly belong to the Nitrososphaerales, which are known as
      important ammonia oxidizers. Multivariate analyses indicated no relationships
      between nutrient data and microbial community structure. However, the aqueous
      geochemical simulations suggest that the microbial communities were not nutrient
      limited because of the equilibrium of snow with the nutrient-rich and fast
      dissolving volcanic ash. Increasing algal secondary carotenoid contents in the
      last stages of the melt seasons have previously been associated with a decrease
      in surface albedo, which in turn could potentially have an impact on the melt
      rates of Icelandic glaciers. 

PMID- 25941517
TI  - Microbial communication leading to the activation of silent fungal secondary
      metabolite gene clusters.
AB  - Microorganisms form diverse multispecies communities in various ecosystems. The
      high abundance of fungal and bacterial species in these consortia results in
      specific communication between the microorganisms. A key role in this
      communication is played by secondary metabolites (SMs), which are also called
      natural products. Recently, it was shown that interspecies "talk" between
      microorganisms represents a physiological trigger to activate silent gene
      clusters leading to the formation of novel SMs by the involved species. This
      review focuses on mixed microbial cultivation, mainly between bacteria and fungi,
      with a special emphasis on the induced formation of fungal SMs in co-cultures. In
      addition, the role of chromatin remodeling in the induction is examined, and
      methodical perspectives for the analysis of natural products are presented. As an
      example for an intermicrobial interaction elucidated at the molecular level, we
      discuss the specific interaction between the filamentous fungi Aspergillus
      nidulans and Aspergillus fumigatus with the soil bacterium Streptomyces
      rapamycinicus, which provides an excellent model system to enlighten molecular
      concepts behind regulatory mechanisms and will pave the way to a novel avenue of
      drug discovery through targeted activation of silent SM gene clusters through co
      cultivations of microorganisms. 

PMID- 25941519
TI  - A short review of fecal indicator bacteria in tropical aquatic ecosystems:
      knowledge gaps and future directions.
AB  - Given the high numbers of deaths and the debilitating nature of diseases caused
      by the use of unclean water it is imperative that we have an understanding of the
      factors that control the dispersion of water borne pathogens and their respective
      indicators. This is all the more important in developing countries where
      significant proportions of the population often have little or no access to clean
      drinking water supplies. Moreover, and notwithstanding the importance of these
      bacteria in terms of public health, at present little work exists on the
      persistence, transfer and proliferation of these pathogens and their respective
      indicator organisms, e.g., fecal indicator bacteria (FIB) such as Escherichia
      coli and fecal coliforms in humid tropical systems, such as are found in South
      East Asia or in the tropical regions of Africa. Both FIB and the waterborne
      pathogens they are supposed to indicate are particularly susceptible to shifts in
      water flow and quality and the predicted increases in rainfall and floods due to
      climate change will only exacerbate the problems of contamination. This will be
      furthermore compounded by the increasing urbanization and agricultural
      intensification that developing regions are experiencing. Therefore, recognizing
      and understanding the link between human activities, natural process and
      microbial functioning and their ultimate impacts on human health are
      prerequisites for reducing the risks to the exposed populations. Most of the
      existing work in tropical systems has been based on the application of temperate
      indicator organisms, models and mechanisms regardless of their applicability or
      appropriateness for tropical environments. Here, we present a short review on the
      factors that control FIB dynamics in temperate systems and discuss their
      applicability to tropical environments. We then highlight some of the knowledge
      gaps in order to stimulate future research in this field in the tropics. 

PMID- 25941520
TI  - Ff-nano, short functionalized nanorods derived from Ff (f1, fd, or M13)
      filamentous bacteriophage.
AB  - F-specific filamentous phage of Escherichia coli (Ff: f1, M13, or fd) are long
      thin filaments (860 nm * 6 nm). They have been a major workhorse in display
      technologies and bionanotechnology; however, some applications are limited by the
      high length-to-diameter ratio of Ff. Furthermore, use of functionalized Ff
      outside of laboratory containment is in part hampered by the fact that they are
      genetically modified viruses. We have now developed a system for production and
      purification of very short functionalized Ff-phage-derived nanorods, named Ff
      nano, that are only 50 nm in length. In contrast to standard Ff-derived vectors
      that replicate in E. coli and contain antibiotic-resistance genes, Ff-nano are
      protein-DNA complexes that cannot replicate on their own and do not contain any
      coding sequences. These nanorods show an increased resistance to heating at
      70(?)C in 1% SDS in comparison to the full-length Ff phage of the same coat
      composition. We demonstrate that functionalized Ff-nano particles are suitable
      for application as detection particles in sensitive and quantitative "dipstick"
      lateral flow diagnostic assay for human plasma fibronectin. 

PMID- 25941521
TI  - Gene expression in the mixotrophic prymnesiophyte, Prymnesium parvum, responds to
      prey availability.
AB  - The mixotrophic prymnesiophyte, Prymnesium parvum, is a widely distributed alga
      with significant ecological importance. It produces toxins and can form ecosystem
      disruptive blooms that result in fish kills and changes in planktonic food web
      structure. However, the relationship between P. parvum and its prey on the
      molecular level is poorly understood. In this study, we used RNA-Seq technology
      to study changes in gene transcription of P. parvum in three treatments with
      different microbial populations available as potential prey: axenic P. parvum (no
      prey), bacterized P. paruvm, and axenic P. parvum with ciliates added as prey.
      Thousands of genes were differentially expressed among the three treatments. Most
      notably, transcriptome data indicated that P. parvum obtained organic carbon,
      including fatty acids, from both bacteria and ciliate prey for energy and
      cellular building blocks. The data also suggested that different prey provided P.
      parvum with macro- and micro-nutrients, namely organic nitrogen in the form of
      amino acids from ciliates, and iron from bacteria. However, both transcriptomic
      data and growth experiments indicated that P. parvum did not grow faster in the
      presence of prey despite the gains in nutrients, although algal abundances
      attained in culture were slightly greater in the presence of prey. The
      relationship between phototrophy, heterotrophy and growth of P. parvum is
      discussed. 

PMID- 25941522
TI  - What difference does it make if viruses are strain-, rather than species
      specific?
AB  - Theoretical work has suggested an important role of lytic viruses in controlling
      the diversity of their prokaryotic hosts. Yet, providing strong experimental or
      observational support (or refutation) for this has proven evasive. Such models
      have usually assumed "host groups" to correspond to the "species" level,
      typically delimited by 16S rRNA gene sequence data. Recent model developments
      take into account the resolution of species into strains with differences in
      their susceptibility to viral attack. With strains as the host groups, the models
      will have explicit viral control of abundance at strain level, combined with
      explicit predator or resource control at community level, but the direct viral
      control at species level then disappears. Abundance of a species therefore
      emerges as the combination of how many strains, and at what abundance, this
      species can establish in competition with other species from a seeding community.
      We here discuss how species diversification and strain diversification may
      introduce competitors and defenders, respectively, and that the balance between
      the two may be a factor in the control of species diversity in mature natural
      communities. These models can also give a dominance of individuals from strains
      with high cost of resistance; suggesting that the high proportion of "dormant"
      cells among pelagic heterotrophic prokaryotes may reflect their need for
      expensive defense rather than the lack of suitable growth substrates in their
      environment. 

PMID- 25941523
TI  - Bacteria may have multiple replication origins.

PMID- 25941524
TI  - Structural basis of RND-type multidrug exporters.
AB  - Bacterial multidrug exporters are intrinsic membrane transporters that act as
      cellular self-defense mechanism. The most notable characteristics of multidrug
      exporters is that they export a wide range of drugs and toxic compounds. The
      overexpression of these exporters causes multidrug resistance. Multidrug
      resistant pathogens have become a serious problem in modern chemotherapy. Over
      the past decade, investigations into the structure of bacterial multidrug
      exporters have revealed the multidrug recognition and export mechanisms. In this
      review, we primarily discuss RND-type multidrug exporters particularly AcrAB
      TolC, major drug exporter in Gram-negative bacteria. RND-type drug exporters are
      tripartite complexes comprising a cell membrane transporter, an outer membrane
      channel and an adaptor protein. Cell membrane transporters and outer membrane
      channels are homo-trimers; however, there is no consensus on the number of
      adaptor proteins in these tripartite complexes. The three monomers of a cell
      membrane transporter have varying conformations (access, binding, and extrusion)
      during transport. Drugs are exported following an ordered conformational change
      in these three monomers, through a functional rotation mechanism coupled with the
      proton relay cycle in ion pairs, which is driven by proton translocation.
      Multidrug recognition is based on a multisite drug-binding mechanism, in which
      two voluminous multidrug-binding pockets in cell membrane exporters recognize a
      wide range of substrates as a result of permutations at numerous binding sites
      that are specific for the partial structures of substrate molecules. The
      voluminous multidrug-binding pocket may have numerous binding sites even for a
      single substrate, suggesting that substrates may move between binding sites
      during transport, an idea named as multisite-drug-oscillation hypothesis. This
      hypothesis is consistent with the apparently broad substrate specificity of cell
      membrane exporters and their highly efficient ejection of drugs from the cell.
      Substrates are transported through dual multidrug-binding pockets via the
      peristaltic motion of the substrate translocation channel. Although there are no
      clinically available inhibitors of bacterial multidrug exporters, efforts to
      develop inhibitors based on structural information are underway. 

PMID- 25941525
TI  - Drugs to block cytokine signaling for the prevention and treatment of
      inflammation-induced preterm birth.
AB  - Preterm birth (PTB) at less than 37 weeks of gestation is the leading cause of
      neonatal morbidity and mortality. Intrauterine infection (IUI) due to microbial
      invasion of the amniotic cavity is the leading cause of early PTB (<32 weeks).
      Commensal genital tract Ureaplasma and Mycoplasma species, as well as Gram
      positive and Gram-negative bacteria, have been associated with IUI-induced PTB.
      Bacterial activation of Toll-like receptors and other pattern recognition
      receptors initiates a cascade of inflammatory signaling via the NF-kappaB and p38
      mitogen-activated protein kinase (MAPK) signaling pathways, prematurely
      activating parturition. Antenatal antibiotic treatment has had limited success in
      preventing PTB or fetal inflammation. Administration of anti-inflammatory drugs
      with antibiotics could be a viable therapeutic option to prevent PTB and fetal
      complications in women at risk of IUI and inflammation. In this mini-review, we
      will discuss the potential for anti-inflammatory drugs in obstetric care,
      focusing on the class of drugs termed "cytokine suppressive anti-inflammatory
      drugs" or CSAIDs. These inhibitors work by specifically targeting the NF-kappaB
      and p38 MAPK inflammatory signaling pathways. Several CSAIDs are discussed,
      together with clinical and toxicological considerations associated with the
      administration of anti-inflammatory agents in pregnancy. 

PMID- 25941526
TI  - The Role of CD44 in the Pathophysiology of Chronic Lymphocytic Leukemia.
AB  - CD44 interactions with hyaluronan (HA) play a key role in various malignancies,
      supporting tumor cell migration, adhesion, and survival. In contrast to solid
      tumors, the expression of CD44 standard and variant forms and their functional
      interplay with HA is less understood in hematological malignancies. Chronic
      lymphocytic leukemia (CLL) is a highly abundant B-cell malignancy with a well
      coordinated balance between cell cycle-arrest and proliferation of tumor
      subpopulations. The long-term survival and proliferation of CLL cells requires
      their dynamic interactions with stromal and immune cells in lymphoid organs.
      Interactions of HA with CD44 and HA-mediated motility receptor (RHAMM) contribute
      to CLL cell localization, and hence CLL pathophysiology, by shaping homing,
      interstitial migration, and adhesion of the tumor cells. CD44 can complex with
      key prognostic factors of CLL, particularly CD38 and CD49d, bridging the gap
      between prognosis and cellular function. Here, we review the current evidence for
      the individual and associated contributions of CD44 to CLL pathophysiology, the
      dynamic functional regulation of CD44 upon CLL cell activation, and possible
      therapeutic strategies targeting CD44 in CLL. 

PMID- 25941527
TI  - The complex myeloid network of the liver with diverse functional capacity at
      steady state and in inflammation.
AB  - In recent years, it has been an explosion of information regarding the role of
      various myeloid cells in liver pathology. Macrophages and dendritic cell (DC)
      play crucial roles in multiple chronic liver diseases such as fibrosis and non
      alcoholic fatty liver disease (NAFLD). The complexity of myeloid cell populations
      and the missing exclusive marker combination make the interpretation of the data
      often extremely difficult. The current review aims to summarize the multiple
      roles of macrophages and DCs in chronic liver diseases, especially pointing out
      how these cells influence liver immune and parenchymal cells thereby altering
      liver function and pathology. Moreover, the review outlines the currently known
      marker combinations for the identification of these cell populations for the
      study of their role in liver immunology. 

PMID- 25941528
TI  - The conservative cysteines in transmembrane domain of AtVKOR/LTO1 are critical
      for photosynthetic growth and photosystem II activity in Arabidopsis.
AB  - Thylakoid protein vitamin K epoxide reductase (AtVKOR/LTO1) is involved in
      oxidoreduction. The deficiency of this compound causes pleiotropic defects in
      Arabidopsis thaliana, such as severely stunted growth, smaller sized leaves, and
      delay of flowering. Transgenic complementation of wild-type AtVKOR (VKORWT) to
      vkor mutant lines ultimately demonstrates that the phenotype changes are due to
      this gene. However, whether AtVKOR functions in Arabidopsis through its protein
      oxidoreduction is unknown. To further study the redox-active sites of AtVKOR in
      vivo, a series of plasmids containing cysteine-mutant VKORs were constructed and
      transformed into vkor deficient lines. Compared with transgenic AtVKORWT plants,
      the size of the transgenic plants with a single conservative cysteine mutation
      (VKORC109A, VKORC116A, VKORC195A, and VKORC198A) were smaller, and two double
      cysteine mutations (VKORC109AC116A and VKORC195AC198A) showed significantly
      stunted growth, similar with the vkor mutant line. However, mutations of two non
      conservative cysteines (VKORC46A and VKORC230A) displayed little obvious changes
      in the phenotypes of Arabidopsis. Consistently, the maximum and actual efficiency
      of photosystem II (PSII) in double-cysteine mutation plants decreased
      significantly to the level similar to that of the vkor mutant line both under
      normal growth light and high light. A significantly decreased amount of D1
      protein and increased accumulation of reactive oxygen species were observed in
      two double-cysteine mutations under high light. All of the results above
      indicated that the conservative cysteines in transmembrane domains were the
      functional sites of AtVKOR in Arabidopsis and that the oxidoreductase activities
      of AtVKOR were directly related to the autotrophic photosynthetic growth and PSII
      activity of Arabidopsis thaliana. 

PMID- 25941530
TI  - Arbuscular mycorrhizal symbiosis alters the expression patterns of three key iron
      homeostasis genes, ZmNAS1, ZmNAS3, and ZmYS1, in S deprived maize plants.
AB  - Nicotianamine is an essential molecule for Fe homeostasis in plants, its primary
      precursor is the S-containing compound methionine, and it is biosynthesized by
      the enzyme family of nicotianamine synthases (NASs). In maize, a graminaceous
      plant that follows Strategy II for Fe uptake, ZmNAS genes can be subgrouped into
      two classes, according to their roles and tissue specific expression profiles. In
      roots, the genes of class I provide NA for the production of deoxymugineic acid
      (DMA), which is secreted to the rhizosphere and chelates Fe(III). The Fe(III)-DMA
      complex is then inserted to the root via a ZmYS1 transporter. The genes of class
      II provide NA for local translocation and detoxification of Fe in the leaves. Due
      to the connection between S and Fe homeostasis, S deficiency causes Fe
      deprivation responses to graminaceous plants and when S is supplied, these
      responses are inverted. In this study, maize plants were grown in pots with
      sterile river sand containing FePO4 and were inoculated with the mycorrhizal
      fungus Rhizophagus irregularis. The plants were grown under S deficient
      conditions until day 60 from sowing and on that day sulfate was provided to the
      plants. In order to assess the impact of AM symbiosis on Fe homeostasis, the
      expression patterns of ZmNAS1, ZmNAS3 (representatives of ZmNAS class I and class
      II), and ZmYS1 were monitored before and after S supply by means of real time RT
      PCR and they were used as indicators of the plant Fe status. In addition, total
      shoot Fe concentration was determined before and after S supply. AM symbiosis
      prevented Fe deprivation responses in the S deprived maize plants and iron was
      possibly provided directly to the mycorrhizal plants through the fungal network.
      Furthermore, sulfate possibly regulated the expression of all three genes
      revealing its potential role as signal molecule for Fe homeostasis. 

PMID- 25941531
TI  - Is watching television a realistic leisure option for people with dementia?
AB  - BACKGROUND: Watching television is a common leisure activity, not least among
      older people. However, watching television may become difficult when it is
      disturbed by symptoms of dementia. METHOD: A total of 284 questionnaires were
      handed out to relatives of people with dementia in Iceland, in the Memory Clinic
      of the University Hospital and in specialized units for people with dementia (6
      day-care units and 8 units within nursing homes). The response rate was just
      below 58%. RESULTS: Watching television was shown to play a less important role
      in the course of the daily life of people with dementia as soon as the symptoms
      of the disease became evident, and it increasingly became less relevant. So, this
      previous leisure activity left an ever-growing void of time to fill. However,
      watching television may provide an important social context for contact and
      togetherness during the progress of the disease, as watching television with
      someone close to them was important for the individuals with dementia.
      CONCLUSION: It is not a viable option for people with dementia to watch
      television on their own, but they may enjoy watching television while sharing
      this activity with a person close to them. This may even provide quality time.

PMID- 25941529
TI  - Temporal aspects of copper homeostasis and its crosstalk with hormones.
AB  - To cope with the dual nature of copper as being essential and toxic for cells,
      plants temporarily adapt the expression of copper homeostasis components to
      assure its delivery to cuproproteins while avoiding the interference of potential
      oxidative damage derived from both copper uptake and photosynthetic reactions
      during light hours. The circadian clock participates in the temporal organization
      of coordination of plant nutrition adapting metabolic responses to the daily
      oscillations. This timely control improves plant fitness and reproduction and
      holds biotechnological potential to drive increased crop yields. Hormonal
      pathways, including those of abscisic acid, gibberellins, ethylene, auxins, and
      jasmonates are also under direct clock and light control, both in mono and
      dicotyledons. In this review, we focus on copper transport in Arabidopsis
      thaliana and Oryza sativa and the presumable role of hormones in metal
      homeostasis matching nutrient availability to growth requirements and preventing
      metal toxicity. The presence of putative hormone-dependent regulatory elements in
      the promoters of copper transporters genes suggests hormonal regulation to match
      special copper requirements during plant development. Spatial and temporal
      processes that can be affected by hormones include the regulation of copper
      uptake into roots, intracellular trafficking and compartmentalization, and long
      distance transport to developing vegetative and reproductive tissues. In turn,
      hormone biosynthesis and signaling are also influenced by copper availability,
      which suggests reciprocal regulation subjected to temporal control by the central
      oscillator of the circadian clock. This transcriptional regulatory network,
      coordinates environmental and hormonal signaling with developmental pathways to
      allow enhanced micronutrient acquisition efficiency. 

PMID- 25941532
TI  - Meta gene set enrichment analyses link miR-137-regulated pathways with
      schizophrenia risk.
AB  - BACKGROUND: A single nucleotide polymorphism (SNP) within MIR137, the host gene
      for miR-137, has been identified repeatedly as a risk factor for schizophrenia.
      Previous genetic pathway analyses suggest that potential targets of this microRNA
      (miRNA) are also highly enriched in schizophrenia-relevant biological pathways,
      including those involved in nervous system development and function. METHODS: In
      this study, we evaluated the schizophrenia risk of miR-137 target genes within
      these pathways. Gene set enrichment analysis of pathway-specific miR-137 targets
      was performed using the stage 1 (21,856 subjects) schizophrenia genome wide
      association study data from the Psychiatric Genomics Consortium and a small
      independent replication cohort (244 subjects) from the Mind Clinical Imaging
      Consortium and Northwestern University. RESULTS: Gene sets of potential miR-137
      targets were enriched with variants associated with schizophrenia risk, including
      target sets involved in axonal guidance signaling, Ephrin receptor signaling,
      long-term potentiation, PKA signaling, and Sertoli cell junction signaling. The
      schizophrenia-risk association of SNPs in PKA signaling targets was replicated in
      the second independent cohort. CONCLUSIONS: These results suggest that these
      biological pathways may be involved in the mechanisms by which this MIR137
      variant enhances schizophrenia risk. SNPs in targets and the miRNA host gene may
      collectively lead to dysregulation of target expression and aberrant functioning
      of such implicated pathways. Pathway-guided gene set enrichment analyses should
      be useful in evaluating the impact of other miRNAs and target genes in different
      diseases.

PMID- 25941533
TI  - Systematic genome assessment of B-vitamin biosynthesis suggests co-operation
      among gut microbes.
AB  - The human gut microbiota supplies its host with essential nutrients, including B
      vitamins. Using the PubSEED platform, we systematically assessed the genomes of
      256 common human gut bacteria for the presence of biosynthesis pathways for eight
      B-vitamins: biotin, cobalamin, folate, niacin, pantothenate, pyridoxine,
      riboflavin, and thiamin. On the basis of the presence and absence of genome
      annotations, we predicted that each of the eight vitamins was produced by 40-65%
      of the 256 human gut microbes. The distribution of synthesis pathways was
      diverse; some genomes had all eight biosynthesis pathways, whereas others
      contained no de novo synthesis pathways. We compared our predictions to
      experimental data from 16 organisms and found 88% of our predictions to be in
      agreement with published data. In addition, we identified several pairs of
      organisms whose vitamin synthesis pathway pattern complemented those of other
      organisms. This analysis suggests that human gut bacteria actively exchange B
      vitamins among each other, thereby enabling the survival of organisms that do not
      synthesize any of these essential cofactors. This result indicates the co
      evolution of the gut microbes in the human gut environment. Our work presents the
      first comprehensive assessment of the B-vitamin synthesis capabilities of the
      human gut microbiota. We propose that in addition to diet, the gut microbiota is
      an important source of B-vitamins, and that changes in the gut microbiota
      composition can severely affect our dietary B-vitamin requirements. 

PMID- 25941535
TI  - Can we identify women who initiate and then prematurely cease breastfeeding? An
      Australian multicentre cohort study.
AB  - BACKGROUND: Health authorities recommend 6 months of fully breastfeeding and
      continuation of breastfeeding for at least a year. Many women initiate
      breastfeeding in hospital but discontinue before the six-month period, and
      therefore do not optimise the public health benefits. The aim of this study was
      to determine whether these women could be identified at hospital discharge, to
      enable targeted interventions. METHODS: A secondary analysis of women who
      intended to breastfeed and were enrolled in a large randomised trial was
      undertaken. Women were enrolled in the antenatal period and antenatal, delivery
      and six month postnatal questionnaires were completed. Univariate and
      multivariate analyses were undertaken to determine the variables associated with
      early cessation of breastfeeding within six months, compared to women who
      continued to breastfeed. RESULTS: Of 2148 women who initiated breastfeeding in
      hospital, 877 continued to breastfed either partially (N = 262) or fully (N =
      615) until six months postpartum and 1271 ceased breastfeeding early. Median
      breastfeeding duration in women who ceased early was 3(+6) weeks (IQR 1(+1) to
      11(+2) weeks). In multivariate analysis, factors that were significantly
      associated with early cessation of breastfeeding were maternal factors of lower
      education (less than 12 years of schooling, no completion of further education),
      smoking (pre-pregnancy or during pregnancy), and newborn factors of preterm birth
      and low birthweight (all p < 0.01). These variables correctly identify 83% of
      women. CONCLUSION: We can identify women who initiate and then prematurely
      discontinue breastfeeding prior to hospital discharge. Evaluation of additional
      interventions to support longer duration of breastfeeding in women at risk of
      ceasing prematurely is needed.

PMID- 25941536
TI  - An experimental method to study emissions from heated tobacco between 100-200
      degrees C.
AB  - BACKGROUND: Cigarette smoke emissions are mainly produced by distillation,
      pyrolysis and combustion reactions when the tobacco is burnt. Some studies have
      shown that heating tobacco to temperatures below pyrolysis and combustion
      temperatures has the potential to reduce or eliminate some toxicants found in
      cigarette smoke. In this study, we designed a bench-top tube furnace that heats
      tobacco between 100-200 degrees C and systematically studied the effects of
      heating temperatures on selected gas phase and aerosol phase compounds using an
      ISO machine-smoking protocol. RESULTS: Among a list of target chemical compounds,
      seven toxicants (nicotine, carbon monoxide, acetaldehyde, crotonaldehyde,
      formaldehyde, NNN and NNK) were quantifiable but not at all temperatures
      examined. The levels of the compounds generally displayed an increasing trend
      with increasing temperatures. The observed carbon monoxide and aldehydes
      represented the initial thermal breakdown products from the tobacco constituents.
      Water was the largest measured component in the total aerosol phase collected and
      appeared to be mainly released by evaporation; nicotine release characteristics
      were consistent with bond breaking and evaporation. Quantifiable levels of NNK
      and NNN were thought to be the result of evaporative transfer from the tobacco
      blend. CONCLUSIONS: These results demonstrate the practical utility of this tool
      to study low-temperature toxicant formation and emission from heated tobacco.
      Between 100 to 200 degrees C, nicotine and some cigarette smoke compounds were
      released as a result of evaporative transfer or initial thermal decomposition
      from the tobacco blend.

PMID- 25941534
TI  - A review of study designs and statistical methods for genomic epidemiology
      studies using next generation sequencing.
AB  - Results from numerous linkage and association studies have greatly deepened
      scientists' understanding of the genetic basis of many human diseases, yet some
      important questions remain unanswered. For example, although a large number of
      disease-associated loci have been identified from genome-wide association studies
      in the past 10 years, it is challenging to interpret these results as most
      disease-associated markers have no clear functional roles in disease etiology,
      and all the identified genomic factors only explain a small portion of disease
      heritability. With the help of next-generation sequencing (NGS), diverse types of
      genomic and epigenetic variations can be detected with high accuracy. More
      importantly, instead of using linkage disequilibrium to detect association
      signals based on a set of pre-set probes, NGS allows researchers to directly
      study all the variants in each individual, therefore promises opportunities for
      identifying functional variants and a more comprehensive dissection of disease
      heritability. Although the current scale of NGS studies is still limited due to
      the high cost, the success of several recent studies suggests the great potential
      for applying NGS in genomic epidemiology, especially as the cost of sequencing
      continues to drop. In this review, we discuss several pioneer applications of
      NGS, summarize scientific discoveries for rare and complex diseases, and compare
      various study designs including targeted sequencing and whole-genome sequencing
      using population-based and family-based cohorts. Finally, we highlight recent
      advancements in statistical methods proposed for sequencing analysis, including
      group-based association tests, meta-analysis techniques, and annotation tools for
      variant prioritization. 

PMID- 25941537
TI  - A pilot, longitudinal, 24-week study to evaluate the effect of interferon beta-1a
      subcutaneous on changes in susceptibility-weighted imaging-filtered phase
      assessment of lesions and subcortical deep-gray matter in relapsing-remitting
      multiple sclerosis.
AB  - BACKGROUND: Studies have shown a relationship between increased iron content and
      clinical progression, cognitive impairment, and brain atrophy in patients with
      multiple sclerosis. Altered phase, as determined by susceptibility-weighted
      imaging (SWI), can potentially capture iron content changes. OBJECTIVE: The
      objective of this study was to investigate phase changes in white matter (WM)
      lesions and subcortical deep-gray matter (SDGM) of patients with relapsing
      remitting (RR) MS treated with interferon beta-1a administered subcutaneously
      versus untreated healthy controls (HCs). METHODS: We conducted a 24-week,
      nonrandomized, open-label pilot study of 23 patients with RRMS receiving
      interferon beta-1a administered subcutaneously and 15 HCs. Patients were imaged
      on a 3T scanner at baseline, 12, and 24 weeks; changes in phase behavior in WM
      lesions and regional SDGM [mean phase of low-phase voxels (MP-LPV)], and in SDGM
      volumes, were measured. Between- and within-group changes were tested using
      nonparametric statistics adjusted for multiple comparisons. RESULTS: The number
      (p = 0.003) and volume (p < 0.001) of phase WM lesions both significantly
      decreased among RRMS patients over 24 weeks. At baseline, MP-LPV was lower
      (suggestive of greater iron content) in total SDGM among RRMS patients versus HCs
      (p = 0.002). Week 24 MP-LPV changes from baseline were not significantly
      different between groups in total SDGM or any region except the putamen (-0.0025
      radians in RRMS patients versus 0.0035 radians in HCs; p = 0.041). CONCLUSIONS:
      Over 24 weeks, phase lesions were reduced significantly in the RRMS group. These
      preliminary results suggest that SWI-filtered phase may become a useful tool for
      monitoring RRMS disease activity.

PMID- 25941538
TI  - The pathogenesis of multifocal motor neuropathy and an update on current
      management options.
AB  - Multifocal motor neuropathy (MMN) is a rare and disabling disease. Several
      experimental studies and clinical data are strongly suggestive of an immune
      mediated pathogenesis, although underlying mechanisms in MMN seem to be very
      specific, mainly because of the presence of IgM anti-GM1 serum antibodies and the
      dramatic response to intravenous immunoglobulins (IVIg). The origin of
      antiganglioside antibodies and the way in which they act at the molecular level
      remain unclear. Several studies have demonstrated the key role of complement
      activation in the underlying mechanisms of MMN, as well as in animal models of
      acute motor axonal neuropathy (AMAN). Deposition of the membrane attack complex
      may disrupt the architecture of the nodes of Ranvier and paranodal areas, causing
      local disruption of nodal sodium-channel clusters. In patients with MMN, muscle
      weakness is the consequence of conduction blocks (CB), which leads to secondary
      axonal degeneration, consequently the aim of the treatment is to reverse CB at
      early stages of the disease. High-dose immunoglobulin is to date the only therapy
      which has proven efficacy in MMN patients in providing transient improvement of
      muscle strength, but long-term follow-up studies show a progressive motor
      decline. Therefore, other therapies are needed to improve the conduction nerve
      properties in long-term design. The reduction of complement activation and more
      generally the gain in paranodal stabilization could be directions for future
      therapeutic strategies. 

PMID- 25941539
TI  - Exercise in the management of persons with multiple sclerosis.
AB  - For decades, persons with multiple sclerosis (MS) were counseled to avoid
      excessive physical activity and exercise because of concerns about worsening
      disease activity. Recent studies indicate that, not only can those with MS
      tolerate physical exercise, but that it is helpful in managing symptoms,
      preventing complications and comorbidities, and may possibly have neuroprotective
      actions. This article reviews previous studies on the effects of different
      exercise protocols in people with MS, and provides summaries of suggested
      exercise regimens that may be appropriate and beneficial for this patient
      population. 

PMID- 25941540
TI  - A review of the efficacy and safety of extended-release topiramate in the
      adjunctive treatment for refractory partial-onset seizures.
AB  - Topiramate has been widely utilized worldwide as an effective medication against
      partial- and generalized-onset seizures. Extended-release topiramate was
      developed to provide patients with the convenience of once-daily dosing and
      potentially improved tolerability by reducing serum concentration fluctuation.
      USL255 is a once-daily, extended-release formulation of topiramate, which was
      recently approved in the USA. Compared with immediate-release topiramate taken
      twice daily, once-daily USL255 provides equivalent topiramate exposure with a 26%
      reduction in plasma fluctuations. A multinational, phase III, randomized, double
      blind, placebo-controlled clinical trial in patients with refractory partial
      onset seizures demonstrated that USL255 (200 mg/day) significantly improved
      seizure control and was well tolerated with low overall neuropsychiatric and
      neurocognitive adverse events. 

PMID- 25941541
TI  - The AMPA receptor antagonist perampanel in the adjunctive treatment of partial
      onset seizures: clinical trial evidence and experience.
AB  - More than 20 antiepileptic drugs (AEDs) are currently available for the medical
      treatment of epilepsies. However, still about 30% of all epilepsies have a drug
      resistant course. Even worse, in the case of some epilepsy syndromes, freedom
      from seizures is almost never achieved. Therefore, new treatment options are
      still necessary, especially if theoretical concepts such as a new mode of action
      offer new horizons. Perampanel is the first-in-class orally active, selective,
      noncompetitive antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid (AMPA) receptors. The pharmacokinetic profile offers once-daily dosing in
      the evening as the best route of administration. According to the results of
      three pivotal placebo-controlled, double-blind phase III trials that investigated
      perampanel as an adjunctive AED in adult and adolescent patients from age 12
      years who had ongoing focal epileptic seizures despite receiving one to three
      AEDs, perampanel has been widely licensed and introduced. Phase III trials showed
      superiority of adjunctive perampanel over placebo consistently in the range
      between 4 and 12 mg. Dizziness and somnolence were by far the leading adverse
      events. This review covers the clinical trial evidence but also clinical
      experience with perampanel after launch according to observational studies. 

PMID- 25941543
TI  - Our scope expansion to include biologics.

PMID- 25941542
TI  - Novel APC promoter and exon 1B deletion and allelic silencing in three mutation
      negative classic familial adenomatous polyposis families.
AB  - BACKGROUND: The overwhelming majority (approximately 80%) of individuals with
      classic familial adenomatous polyposis (FAP) exhibit mutations in the coding
      sequence of the adenomatous polyposis coli (APC) tumor suppressor gene. Families
      without detectable APC mutations are unable to benefit from the use of genetic
      testing for clinical management of this autosomal dominant syndrome. METHODS: We
      used exome sequencing and linkage analysis, coupled with second-generation
      sequencing of the APC locus including non-coding regions to investigate three APC
      mutation-negative classical FAP families. RESULTS: We identified a novel ~11 kb
      deletion localized 44 kb upstream of the transcription start site of APC that
      encompasses the APC 1B promoter and exon. This deletion was present only in
      affected family members of one kindred with classical FAP. Furthermore, this same
      deletion with identical breakpoints was found in the probands of two additional
      APC mutation-negative classical FAP kindreds. Phasing analysis of single
      nucleotide polymorphisms (SNPs) around the deletion site in the three probands
      showed evidence of a shared haplotype, suggesting a common founder deletion in
      the three kindreds. SNP analysis within the coding sequence of APC, revealed that
      this ~11 kb deletion was accompanied by silencing of one of the APC alleles in
      blood-derived RNA of affected individuals. CONCLUSIONS: These results support the
      causal role of a novel promoter deletion in FAP and suggest that non-coding
      deletions, identifiable using second-generation sequencing methods, may account
      for a significant fraction of APC mutation-negative classical FAP families.

PMID- 25941544
TI  - Screening-based translation of public research encounters painful problems.
AB  - Whether identified through high throughput screening or in silico screening, and
      whether target-based or phenotypic, sets of hits will contain chemical con
      artists. Such pan-assay interference compounds (PAINS) and other subversive
      compounds continue to pollute the scientific literature. There are several angles
      of attack to aid identification of such nonprogressable molecules. One of these
      rules above all, and this is a demonstration of genuine structure-activity
      relationships. Recognition of this, which will require a greater effort in
      medicinal chemistry, will be of general benefit. 

PMID- 25941545
TI  - Biphenyl-ethyl-pyrrolidine derivatives as histamine h3 receptor modulators for
      the treatment of cognitive disorders.

PMID- 25941546
TI  - 4,6-Diarylaminothiazines as BACE1 Inhibitors and Their Use for the Reduction of
      Beta-Amyloid Production.

PMID- 25941547
TI  - Discovery of imidazopyridine derivatives as highly potent respiratory syncytial
      virus fusion inhibitors.
AB  - A series of imidazolepyridine derivatives were designed and synthesized according
      to the established docking studies. The imidazopyridine derivatives were found to
      have good potency and physical-chemical properties. Several highly potent
      compounds such as 8ji, 8jl, and 8jm were identified with single nanomolar
      activities. The most potent compound 8jm showed an IC50 of 3 nM, lower microsome
      clearance and no CYP inhibition. The profile of 8jm appeared to be superior to
      BMS433771, and supported further optimization. 

PMID- 25941548
TI  - Protecting chemistry inventions: the double-edged sword of being an unpredictable
      art.
AB  - Recent decisions by the highest courts in the US in regard to written description
      and enablement as well as parallel restrictions previously established in Europe
      emphasize that applicants in the fields of chemistry/pharma/life sciences should
      strive to include as many examples, data, and guidance about how to extrapolate
      from the example(s) in the description. This holds in particular whenever a broad
      genus and/or functional features is/are to be protected. It is important to keep
      in mind that these data and this guidance must be disclosed in the application at
      the time of filing. Data collected at a later stage can only be used to further
      support data and evidence already present in the application as filed. 

PMID- 25941549
TI  - Melanin-concentrating hormone receptor 1 antagonists for treatment of obesity.

PMID- 25941550
TI  - Fibroblast Growth Factor Receptor 3 (FGF-R3): A Promising Therapeutic Target for
      the Treatment of Bladder Cancer.

PMID- 25941551
TI  - Rho kinase inhibitors: potentially versatile therapy for the treatment of
      cardiovascular diseases and more.

PMID- 25941552
TI  - Decaprenylphosphoryl-beta-d-ribose 2'-Epimerase 1 (DprE1): A Novel Therapeutic
      Target for the Treatment of Tuberculosis.

PMID- 25941553
TI  - Design and synthesis of novel arctigenin analogues for the amelioration of
      metabolic disorders.
AB  - Analogues of the natural product (-)-arctigenin, an activator of adenosine
      monophosphate activated protein kinase, were prepared in order to evaluate their
      effects on 2-deoxyglucose uptake in L6 myotubes and possible use in ameliorating
      metabolic disorders. Racemic arctigenin 2a was found to display a similar uptake
      enhancement as does (-)-arctigenin. As a result, the SAR study was conducted
      utilizing racemic compounds. The structure-activity relationship study led to the
      discovery of key substitution patterns on the lactone motif that govern 2
      deoxyglucose uptake activities. The results show that replacement of the para
      hydroxyl group of the C-2 benzyl moiety of arctigenin by Cl has a pronounced
      effect on uptake activity. Specifically, analogue 2p, which contains the p-Cl
      substituent, stimulates glucose uptake and fatty acid oxidation in L6 myotubes. 

PMID- 25941554
TI  - Mitochondria-Localized Fluorescent BODIPY-Platinum Conjugate.
AB  - A convenient synthesis of a BODIPY (1,3,5,7-tetramethyl-8-(4-pyridyl)-4,4'
      difluoroboradiazaindacene) labeled platinum compound (BODIPY-Pt) was developed by
      direct conjugation of cisplatin with the pyridine group of BODIPY. The membrane
      permeability and selective uptake of BODIPY-Pt in the mitochondria was studied
      using confocal laser scanning microscopy (CLSM). The fluorescent BODIPY-Pt
      conjugate showed high cellular proliferation inhibition against human cervical
      carcinoma (HeLa) and human breast cancer (MCF-7) cells, with half maximal
      inhibitory concentrations (IC50) of 27.37 and 12.14 MUM, respectively. This work
      highlights the potential of using BODIPY labeled Pt compounds to realize the
      visualization of Pt distribution in living cells. 

PMID- 25941555
TI  - Discovery of benzimidazole oxazolidinediones as novel and selective nonsteroidal
      mineralocorticoid receptor antagonists.
AB  - Elaboration of the oxazolidinedione series led to replacement of the exocyclic
      amides with substituted benzimidazoles. The structure-activity relationship (SAR)
      exploration resulted in the discovery of potent and selective nonsteroidal
      mineralocorticoid receptor (MR) antagonists with significantly improved
      microsomal stability and pharmacokinetic (PK) profile relative to the HTS hit 1a.
      One compound 2p possessed comparable efficacy as spironolactone (SPL) at 100
      mg/kg (p.o.) in the rat natriuresis model. As such, this series was validated as
      a lead series for further optimization. 

PMID- 25941556
TI  - Membrane-Targeting DCAP Analogues with Broad-Spectrum Antibiotic Activity against
      Pathogenic Bacteria.
AB  - We performed a structure-activity relationship study of 2-((3-(3,6-dichloro-9H
      carbazol-9-yl)-2-hydroxypropyl)amino)-2-(hydroxymethyl)propane-1,3-diol (DCAP),
      which is an antibacterial agent that disrupts the membrane potential and
      permeability of bacteria. The stereochemistry of DCAP had no effect on the
      biological activity of DCAP. The aromaticity and electronegativity of the
      chlorine-substituted carbazole was required for activity, suggesting that its
      planar and dipolar characteristics orient DCAP in membranes. Increasing the
      hydrophobicity of the tail region of DCAP enhanced its antibiotic activity. Two
      DCAP analogues displayed promising antibacterial activity against the BSL-3
      pathogens Bacillus anthracis and Francisella tularensis. Codosing DCAP analogues
      with ampicillin or kanamycin increased their potency. These studies demonstrate
      that DCAP and its analogues may be a promising scaffold for developing
      chemotherapeutic agents that bind to bacterial membranes and kill strains of slow
      growing or dormant bacteria that cause persistent infections. 

PMID- 25941557
TI  - Tying up Nicotine: New Selective Competitive Antagonist of the Neuronal Nicotinic
      Acetylcholine Receptors.
AB  - Conformational restriction of the pyrrolidine nitrogen in nicotine by the
      introduction of an ethylene bridge provided a potent and selective antagonist of
      the alpha4beta2-subtype of the nicotinic acetylcholine receptors. Resolution by
      chiral SFC, pharmacological characterization of the two enantiomers, and
      determination of absolute configuration via enantioselective synthesis showed
      that the pharmacological activity resided almost exclusively in the (R)
      enantiomer. 

PMID- 25941558
TI  - Synthesis and Biological Activities of 5-Thio-alpha-GalCers.
AB  - NKT cells, a unique subset of T cells that recognizes glycolipid antigens
      presented by CD1d molecules, are believed to produce key cytokines of both Th1
      and Th2 T cells and are thus involved in the control of several types of immune
      response. As an active glycolipid antigen having alpha-galactosyl ceramide core
      structure, KRN7000 showed promising immunostimulation activity and was selected
      as an anticancer drug candidate for further clinical application. In this report,
      three new KRN7000 structural analogues were designed and synthesized, in which
      the ring oxygen of the galactopyranose residue is replaced by a sulfur atom along
      with the variation on the lipid chain. Their abilities for stimulating mouse NKT
      cells to produce IFN-gamma and IL-4 were evaluated both in vivo and in vitro. 

PMID- 25941559
TI  - Switch in Site of Inhibition: A Strategy for Structure-Based Discovery of Human
      Topoisomerase IIalpha Catalytic Inhibitors.
AB  - A study of structure-based modulation of known ligands of hTopoIIalpha, an
      important enzyme involved in DNA processes, coupled with synthesis and in vitro
      assays led to the establishment of a strategy of rational switch in mode of
      inhibition of the enzyme's catalytic cycle. 6-Arylated derivatives of known
      imidazopyridine ligands were found to be selective inhibitors of hTopoIIalpha,
      while not showing TopoI inhibition and DNA binding. Interestingly, while the
      parent imidazopyridines acted as ATP-competitive inhibitors, arylated derivatives
      inhibited DNA cleavage similar to merbarone, indicating a switch in mode of
      inhibition from ATP-hydrolysis to the DNA-cleavage stage of catalytic cycle of
      the enzyme. The 6-aryl-imidazopyridines were relatively more cytotoxic than
      etoposide in cancer cells and less toxic to normal cells. Such unprecedented
      strategy will encourage research on "choice-based change" in target-specific mode
      of action for rapid drug discovery. 

PMID- 25941560
TI  - Effect of mutations on the thermostability of Aspergillus aculeatus beta-1,4
      galactanase.
AB  - New variants of beta-1,4-galactanase from the mesophilic organism Aspergillus
      aculeatus were designed using the structure of beta-1,4-galactanase from the
      thermophile organism Myceliophthora thermophila as a template. Some of the
      variants were generated using PROPKA 3.0, a validated pKa prediction tool, to
      test its usefulness as an enzyme design tool. The PROPKA designed variants were
      D182N and S185D/Q188T, G104D/A156R. Variants Y295F and G306A were designed by a
      consensus approach, as a complementary and validated design method. D58N was a
      stabilizing mutation predicted by both methods. The predictions were
      experimentally validated by measurements of the melting temperature (Tm ) by
      differential scanning calorimetry. We found that the Tm is elevated by 1.1 
      degrees C for G306A, slightly increased (in the range of 0.34 to 0.65  degrees C)
      for D182N, D58N, Y295F and unchanged or decreased for S185D/Q188T and
      G104D/A156R. The Tm changes were in the range predicted by PROPKA. Given the
      experimental errors, only the D58N and G306A show significant increase in
      thermodynamic stability. Given the practical importance of kinetic stability, the
      kinetics of the irreversible enzyme inactivation process were also investigated
      for the wild-type and three variants and found to be biphasic. The half-lives of
      thermal inactivation were approximately doubled in G306A, unchanged for D182N
      and, disappointingly, a lot lower for D58N. In conclusion, this study tests a new
      method for estimating Tm changes for mutants, adds to the available data on the
      effect of substitutions on protein thermostability and identifies an interesting
      thermostabilizing mutation, which may be beneficial also in other galactanases. 

PMID- 25941562
TI  - Thyroid hormonal status among children with obesity.
AB  - BACKGROUND: It is presumed that free T4 and thyroid-stimulating hormone (TSH)
      levels are related to obesity, but the findings are inconsistent. In this study
      we evaluated T4 and TSH concentrations between normal children and those with
      obesity and possible correlations between body mass index (BMI) and these
      markers. METHODS: In this prospective study, 190 children who were overweight and
      obese and 133 children without obesity of the same age and sex were evaluated.
      Thyroid function tests (TSH, total T4, free T4 and free T3) were measured in all
      subjects in both groups. Thyroid antibodies (thyroid peroxidase and
      thyroglobulin) were determined among those with elevated TSH levels. RESULTS:
      Levels of TSH and total T4 were significantly higher in children with obesity
      compared with the control group. Subclinical hypothyroidism was significantly
      higher in children with obesity (14.7%) compared with normal subjects (6.8%, p =
      0.02). Among children with obesity and increased TSH levels, 10.7% had positive
      thyroid peroxidase and thyroglobulin antibodies. There was significantly positive
      correlation between BMI z score and TSH level (r = 0.198, p < 0.001) and T4 level
      (r = 0.18, p = 0.001). CONCLUSION: TSH and total T4 levels are increased in
      children who are overweight or obese and are a common finding in these children,
      but the incidence of thyroid antibodies is low in these patients and so could not
      be accounted for by thyroid autoimmunity. Due to these findings it is possible
      that increased TSH and total T4 levels are a consequence of obesity and could be
      reduced by decreasing BMI.

PMID- 25941561
TI  - A2aR antagonists: Next generation checkpoint blockade for cancer immunotherapy.
AB  - The last several years have witnessed exciting progress in the development of
      immunotherapy for the treatment of cancer. This has been due in great part to the
      development of so-called checkpoint blockade. That is, antibodies that block
      inhibitory receptors such as CTLA-4 and PD-1 and thus unleash antigen-specific
      immune responses against tumors. It is clear that tumors evade the immune
      response by usurping pathways that play a role in negatively regulating normal
      immune responses. In this regard, adenosine in the immune microenvironment
      leading to the activation of the A2a receptor has been shown to represent one
      such negative feedback loop. Indeed, the tumor microenvironment has relatively
      high concentrations of adenosine. To this end, blocking A2a receptor activation
      has the potential to markedly enhance anti-tumor immunity in mouse models. This
      review will present data demonstrating the ability of A2a receptor blockade to
      enhance tumor vaccines, checkpoint blockade and adoptive T cell therapy. Also, as
      several recent studies have demonstrated that under certain conditions A2a
      receptor blockade can enhance tumor progression, we will also explore the
      complexities of adenosine signaling in the immune response. Despite important
      nuances to the A2a receptor pathway that require further elucidation, studies to
      date strongly support the development of A2a receptor antagonists (some of which
      have already been tested in phase III clinical trials for Parkinson Disease) as
      novel modalities in the immunotherapy armamentarium. 

PMID- 25941563
TI  - The effect of pioglitazone on weight, lipid profile and liver enzymes in type 2
      diabetic patients.
AB  - BACKGROUND: Pioglitazone is one of the antidiabetic agents used in the management
      of type 2 diabetes mellitus (DM). The effect of pioglitazone on blood glucose,
      lipid profile, liver enzymes and weight has been shown with conflicting results.
      In this study we aim to evaluate the effect of pioglitazone on the weight, lipid
      profile and liver enzymes in patients with DM. METHODS: In this single-arm
      clinical trial, 110 poorly controlled diabetic type 2 patients (63.6% female with
      mean age of 54.26 +/- 8.96 years) who were on maximal dosage of metformin and
      glibenclamide were enrolled. Patients were treated with pioglitazone for 3 months
      and laboratory. Fasting blood sugar (FBS), haemoglobin A1C (HbA1C), cholesterol,
      triglyceride, low-density lipoprotein (LDL) and high-density lipoprotein (HDL),
      alkaline phosphatase (ALK-P), alanine aminotransferase (ALT), aspartate
      aminotransferase (AST) and weight changes were measured before and at the end of
      the study. RESULTS: The levels of FBS (p < 0.001), HbA1c (p < 0.001),
      triglyceride (p = 0.001), ALT (p = 0.005) and ALK-P (p = 0.001) were
      significantly decreased, but weight was significantly increased (p < 0.001) after
      the intervention. There were no significant difference in cholesterol, LDL and
      HDL values before and after study. CONCLUSION: Although pioglitazone causes a
      significant decrease in FBS, HbA1C and triglyceride levels, it is associated with
      weight gain, which would limit its utility. IRCT registration code:
      IRCT201209276712N2.

PMID- 25941564
TI  - Update on long-term efficacy and safety of dapagliflozin in patients with type 2
      diabetes mellitus.
AB  - Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of
      antihyperglycaemic agents with an insulin-independent mode of action.
      Dapagliflozin is a member of the SGLT2 inhibitors class that has received
      marketing authorization in Europe and the US for use in patients with type 2
      diabetes. This review summarizes current evidence from clinical trials assessing
      the clinical efficacy and safety of dapagliflozin, and presents data regarding
      its cost-effectiveness. Treatment with dapagliflozin results in similar reduction
      in haemoglobin A1c with other oral antihyperglycaemic drugs, which is preserved
      over 4 years of treatment. However, compared with most antidiabetic agents,
      dapagliflozin provides additional clinical benefits including body weight loss
      and blood pressure reduction. Moreover, treatment with dapagliflozin does not
      increase risk for hypoglycaemia, but is associated with increased incidence of
      mild to moderate urinary and genital tract infections. A pivotal outcomes trial
      of dapagliflozin is expected to clarify its effect on cardiovascular endpoints,
      whilst a causative relationship between dapagliflozin and select malignancies is
      unlikely. Finally, based on recent economic evaluations dapagliflozin seems to be
      a cost-effective option for type 2 diabetes in some settings. 

PMID- 25941565
TI  - Short commentary on empagliflozin and its potential clinical impact.
AB  - Sodium glucose cotransporter type 2 (SGLT2) inhibitors are a new class of drug
      developed to treat type 2 diabetes mellitus (T2DM). They target the kidney by
      reducing renal glucose reabsorption and promoting urinary glucose excretion,
      which reduces hyperglycemia in individuals with T2DM. The SGLT2 inhibitor
      empagliflozin has gained approval in the EU and in the USA for the treatment of
      adults with T2DM (there is no current indication in type 1 diabetes).
      Empagliflozin has shown a good efficacy and safety profile from clinical trials
      when given as monotherapy, and as an add-on therapy to other glucose-lowering
      agents. This short commentary reviews the key efficacy and safety data from
      empagliflozin phase III trials and examines the potential role this agent may
      have in the management of T2DM. 

PMID- 25941566
TI  - "The value of pre- and co-seasonal sublingual immunotherapy in pollen-induced
      allergic rhinoconjunctivitis".
AB  - Allergen immunotherapy (AIT) is a guidelines-approved, disease-modifying
      treatment option for respiratory allergies, including allergic rhinitis (AR)
      induced by pollen. The various AIT regimens employed to date in pollen-induced AR
      can be classified as continuous (i.e. year-round) or discontinuous (i.e. pre
      seasonal alone, co-seasonal alone or pre- and co-seasonal). Pre-and co-seasonal
      regimens are typically used for sublingual allergen immunotherapy (SLIT) and have
      economic and compliance advantages over perennial (year-round) regimens. However,
      these advantages must not come at the expensive of poor efficacy or safety. The
      results of recent double-blind, placebo-controlled, randomized clinical trials
      show that pre- and co-seasonal SLIT is safe and effective in patients with AR
      induced by grass pollen (treated with a tablet formulation) or by birch pollen
      (treated with a liquid formulation). Progress in SLIT has been made in defining
      the optimal dose of major allergen, the administration frequency (daily), the
      duration of pre-seasonal treatment (four months) and the number of treatment
      seasons (at least three). Post-marketing, "real-life" trials of pre- and co
      seasonal birch or grass pollen SLIT regimens have confirmed the efficacy and
      safety observed in the clinical trials. In the treatment of pollen-induced AR,
      pre- and co-seasonal SLIT regimens appear to be at least as effective and safe as
      perennial SLIT regimens, and are associated with lower costs and good compliance.
      Good compliance may mean that pre- and co-seasonal SLIT regimens are inherently
      more effective and safer than perennial SLIT regimens. When considering the pre-
      and co-seasonal discontinuous regimen in particular, a 300 IR five-grass-pollen
      formulation is the only SLIT tablet with a clinical development programme having
      provided evidence of short-term, sustained and post-treatment efficacy. 

PMID- 25941568
TI  - Amyand hernia: Case report and review of the literature.
AB  - INTRODUCTION: Amyand Hernia is a rare disease seen in approximately 1% of all
      hernias, complications of it, like acute appendicitis, or perforated appendicitis
      are even more rare, about 0.1%. Its diagnosis is very difficult in the pre
      operative period; it is usually an incidental finding. PRESENTATION OF CASE: This
      paper describes the case of a forty-year-old male patient, which was presented to
      the outpatient clinic of surgery with an incarcerated right side inguinal hernia
      without any signs of ischemic complications. He was admitted, and an hernioplasty
      was performed, as an incidental finding we encountered an Amyand hernia treated
      without appendectomy and placement of a prosthetic mesh without any
      complications. DISCUSSION: This disease represents a very challenging diagnosis,
      seven years ago the standardization of management had already been established;
      in this case we encountered a type 1 Amyand's Hernia so we performed a standard
      tension free hernioplasty without complications. CONCLUSION: Amyand hernia is a
      rare condition, which represents two of the most common diseases a general
      surgeon has to face. Standardization of treatment is still ongoing and more
      prospective studies need to be done. This case demonstrates that this pathology
      must remain in the mind of the surgeons especially in the event of a strangulated
      hernia and offer a comprehensive review.

PMID- 25941567
TI  - Benchmark datasets for 3D MALDI- and DESI-imaging mass spectrometry.
AB  - BACKGROUND: Three-dimensional (3D) imaging mass spectrometry (MS) is an
      analytical chemistry technique for the 3D molecular analysis of a tissue
      specimen, entire organ, or microbial colonies on an agar plate. 3D-imaging MS has
      unique advantages over existing 3D imaging techniques, offers novel perspectives
      for understanding the spatial organization of biological processes, and has
      growing potential to be introduced into routine use in both biology and medicine.
      Owing to the sheer quantity of data generated, the visualization, analysis, and
      interpretation of 3D imaging MS data remain a significant challenge.
      Bioinformatics research in this field is hampered by the lack of publicly
      available benchmark datasets needed to evaluate and compare algorithms. FINDINGS:
      High-quality 3D imaging MS datasets from different biological systems at several
      labs were acquired, supplied with overview images and scripts demonstrating how
      to read them, and deposited into MetaboLights, an open repository for
      metabolomics data. 3D imaging MS data were collected from five samples using two
      types of 3D imaging MS. 3D matrix-assisted laser desorption/ionization imaging
      (MALDI) MS data were collected from murine pancreas, murine kidney, human oral
      squamous cell carcinoma, and interacting microbial colonies cultured in Petri
      dishes. 3D desorption electrospray ionization (DESI) imaging MS data were
      collected from a human colorectal adenocarcinoma. CONCLUSIONS: With the aim to
      stimulate computational research in the field of computational 3D imaging MS,
      selected high-quality 3D imaging MS datasets are provided that could be used by
      algorithm developers as benchmark datasets.

PMID- 25941569
TI  - Intestinal dysbiosis in children with short bowel syndrome is associated with
      impaired outcome.
AB  - BACKGROUND: The composition of the intestinal microbiota seems to be an important
      factor in determining the clinical outcome in children with short bowel syndrome
      (SBS). Alterations in the microbiota may result in serious complications such as
      small bowel bacterial overgrowth (SBBO) and intestinal mucosal inflammation that
      lead to prolonged parenteral nutrition (PN) dependency with subsequently
      increased risk of liver failure and sepsis. To date, there are no reported
      mappings of the intestinal microbiome in children with SBS. Here, we present the
      first report on the intestinal microbial community profile in children with SBS.
      FINDINGS: The study includes children diagnosed with SBS in the neonatal period.
      Healthy siblings served as controls. Fecal samples were collected, and microbial
      profiles were analyzed by using 16S rRNA gene sequencing on the Illumina MiSeq
      platform. We observed a pronounced microbial dysbiosis in children with SBS on PN
      treatment with an increased and totally dominating relative abundance of
      Enterobacteriacae in four out of five children compared to children with SBS
      weaned from PN and healthy siblings. CONCLUSIONS: The overall decreased bacterial
      diversity in children with SBS is consistent with intestinal microbiome mappings
      in inflammatory bowel diseases such as Crohn's disease and necrotizing
      enterocolitis in preterm infants. Our findings indicate that intestinal dysbiosis
      in children with SBS is associated with prolonged PN dependency.

PMID- 25941570
TI  - Characteristics of patients co-infected with HIV at the time of inpatient
      tuberculosis treatment initiation in Yaounde, Cameroon: a tertiary care hospital
      based cross-sectional study.
AB  - BACKGROUND: Knowledge of the characteristics of patients co-infected with
      tuberculosis (TB) and human immunodeficiency virus (HIV) when TB treatment is
      initiated would allow clinicians to improve care and help policy-makers develop
      relevant and realistic guidelines. The aim of this study was to describe socio
      demographic, clinical, and laboratory characteristics of TB/HIV co-infected
      patients starting inpatient TB treatment in Yaounde, Cameroon. METHODS: We
      conducted a retrospective cross-sectional study, collecting data from medical
      records of HIV-infected patients with TB, aged 15 years old or more, hospitalized
      in the Infectious Diseases Unit of the Yaounde Central Hospital, Cameroon from
      January 1, 2006 to June 30, 2013. RESULTS: The mean age of 337 patients meeting
      study inclusion criteria was 39.3 years. More than half were female (53.4%). Most
      (89.3%) resided in urban areas, 44.2% had a secondary education, and 46.0% were
      married. The majority was receiving co-trimoxazole prophylaxis (79.5%), and two
      thirds were taking antiretroviral therapy (67.4%). The mean duration of known HIV
      infection before TB treatment was 8.4 months. Most (88.1%) had newly diagnosed
      TB, rather than relapsed disease. Smear-positive pulmonary TB was documented in a
      third, (35.3%). Laboratory data revealed a median white blood cell count of 5,100
      cells/mm(3) (IQR 3,300-7,990 cells/mm(3)), a median hemoglobin level of 8 g/dl
      (IQR 7-10 g/dl), and a median CD4 cell count of 102 cells/mm(3) (IQR 33-178
      cells/mm(3)). Sex differences in our study included older age in the men (p <
      0.001), more of whom were married (p < 0.001) and had achieved a higher level of
      education (p = 0.042). Men had fewer diagnoses of smear-positive pulmonary TB (p
      = 0.020). They weighed more than the women (p = 0.001) and had higher hemoglobin
      levels (p = 0.003). CONCLUSIONS: Suboptimal adherence to WHO treatment
      recommendations in our Cameroonian study reinforces the importance of prescribing
      co-trimoxazole in HIV infection and ART for all TB/HIV co-infected persons. We
      urge that Ministries of Health continue implementing and disseminating guidelines
      for management of TB/HIV co-infected patients, and we call for measures ensuring
      that healthcare facilities' stocks of ART and co-trimoxazole are sufficient to
      meet the need for both.

PMID- 25941571
TI  - Opportunities for the application of advanced remotely-sensed data in ecological
      studies of terrestrial animal movement.
AB  - Animal movement patterns in space and time are a central aspect of animal
      ecology. Remotely-sensed environmental indices can play a key role in
      understanding movement patterns by providing contiguous, relatively fine-scale
      data that link animal movements to their environment. Still, implementation of
      newly available remotely-sensed data is often delayed in studies of animal
      movement, calling for a better flow of information to researchers less familiar
      with remotely-sensed data applications. Here, we reviewed the application of
      remotely-sensed environmental indices to infer movement patterns of animals in
      terrestrial systems in studies published between 2002 and 2013. Next, we
      introduced newly available remotely-sensed products, and discussed their
      opportunities for animal movement studies. Studies of coarse-scale movement
      mostly relied on satellite data representing plant phenology or climate and
      weather. Studies of small-scale movement frequently used land cover data based on
      Landsat imagery or aerial photographs. Greater documentation of the type and
      resolution of remotely-sensed products in ecological movement studies would
      enhance their usefulness. Recent advancements in remote sensing technology
      improve assessments of temporal dynamics of landscapes and the three-dimensional
      structures of habitats, enabling near real-time environmental assessment. Online
      movement databases that now integrate remotely-sensed data facilitate access to
      remotely-sensed products for movement ecologists. We recommend that animal
      movement studies incorporate remotely-sensed products that provide time series of
      environmental response variables. This would facilitate wildlife management and
      conservation efforts, as well as the predictive ability of movement analyses.
      Closer collaboration between ecologists and remote sensing experts could
      considerably alleviate the implementation gap. Ecologists should not expect that
      indices derived from remotely-sensed data will be directly analogous to field
      collected data and need to critically consider which remotely-sensed product is
      best suited for a given analysis. 

PMID- 25941572
TI  - Identifying the time scale of synchronous movement: a study on tropical snakes.
AB  - BACKGROUND: Individual movement is critical to organismal fitness and also
      influences broader population processes such as demographic stochasticity and
      gene flow. Climatic change and habitat fragmentation render the drivers of
      individual movement especially critical to understand. Rates of movement of free
      ranging animals through the landscape are influenced both by intrinsic attributes
      of an organism (e.g., size, body condition, age), and by external forces (e.g.,
      weather, predation risk). Statistical modelling can clarify the relative
      importance of those processes, because externally-imposed pressures should
      generate synchronous displacements among individuals within a population, whereas
      intrinsic factors should generate consistency through time within each
      individual. External and intrinsic factors may vary in importance at different
      time scales. RESULTS: In this study we focused on daily displacement of an ambush
      foraging snake from tropical Australia (the Northern Death Adder Acanthophis
      praelongus), based on a radiotelemetric study. We used a mixture of spectral
      representation and Bayesian inference to study synchrony in snake displacement by
      phase shift analysis. We further studied autocorrelation in fluctuations of
      displacement distances as "one over f noise". Displacement distances were
      positively autocorrelated with all considered noise colour parameters estimated
      as >0. We show how the methodology can reveal time scales of particular interest
      for synchrony and found that for the analysed data, synchrony was only present at
      time scales above approximately three weeks. CONCLUSION: We conclude that the
      spectral representation combined with Bayesian inference is a promising approach
      for analysis of movement data. Applying the framework to telemetry data of A.
      praelongus, we were able to identify a cut-off time scale above which we found
      support for synchrony, thus revealing a time scale where global external drivers
      have a larger impact on the movement behaviour. Our results suggest that for the
      considered study period, movement at shorter time scales was primarily driven by
      factors at the individual level; daily fluctuations in weather conditions had
      little effect on snake movement.

PMID- 25941574
TI  - B cells for cancer immunotherapy.
AB  - We have engineered a novel fusion cytokine named GIFT4 derived from GM-CSF and IL
      4, and displaying robust gain-of-function immunostimulatory effects on B cells.
      GIFT4-programmed B cells have a unique identity and potent capacity to elicit a
      tumoricidal - cell response, thus comprising a novel B cell-based cancer
      immunotherapeutic approach.

PMID- 25941575
TI  - Is the scavenger receptor MARCO a new immune checkpoint?
AB  - Whereas macrophages use the scavenger receptor MARCO primarily in antimicrobial
      immunity by interacting with both exogenous and endogenous environments, in
      dendritic cells (DCs) MARCO is believed to pleiotropically link innate to
      adaptive immunity. MARCO exerts a significant modulatory effect on TLR-induced DC
      activation, thus offering novel avenues in cancer immunotherapy.

PMID- 25941576
TI  - Inhibition of MYC in macrophages: tumor vs inflammation-related diseases.
AB  - Inhibition of MYC has been postulated as one of the most promising anti-tumoral
      therapies. However, if some anti-inflammatory cells express MYC, would an anti
      tumoral treatment targeting MYC facilitate subsequent inflammation-related
      disorders?

PMID- 25941577
TI  - Location, location, location: functional and phenotypic heterogeneity between
      tumor-infiltrating and non-infiltrating myeloid-derived suppressor cells.
AB  - An increasing number of studies is focusing on the role of myeloid-derived
      suppressor cells (MDSCs) in the suppression of antitumor immune responses.
      Although the main site of action for MDSCs is most likely the tumor
      microenvironment, the study of these cells has been largely restricted to MDSCs
      derived from peripheral lymphoid organs. Only in a minority of studies MDSCs
      isolated from the tumor microenvironment have been characterized. This review
      will give an overview of the data available on the phenotypical and functional
      differences between tumor-derived MDSCs and MDSCs isolated from the spleen of
      tumor-bearing mice or from the peripheral blood of cancer patients.

PMID- 25941580
TI  - Overcoming immunosuppression to enhance a p53MVA vaccine.
AB  - A Phase I trial of a p53-targeting modified vaccinia Ankara (p53MVA) vaccine in
      patients afflicted with refractory gastrointestinal cancers demonstrated enhanced
      T-cell recognition of p53 following vaccination. However, this effect was
      transient suggesting that p53MVA requires combination with immunomodulatory
      agents to deliver clinical benefit. Here, we outline our rationale for combining
      p53MVA with immunomodulatory chemotherapy in a forthcoming trial.

PMID- 25941579
TI  - Local treatment of a pleural mesothelioma tumor with ONCOS-102 induces a systemic
      antitumor CD8+ T-cell response, prominent infiltration of CD8+ lymphocytes and
      Th1 type polarization.
AB  - Late stage cancer is often associated with reduced immune recognition and a
      highly immunosuppressive tumor microenvironment. The presence of tumor
      infiltrating lymphocytes (TILs) and specific gene-signatures prior to treatment
      are linked to good prognosis, while the opposite is true for extensive
      immunosuppression. The use of adenoviruses as cancer vaccines is a form of active
      immunotherapy to initialise a tumor-specific immune response that targets the
      patient's unique tumor antigen repertoire. We report a case of a 68-year-old male
      with asbestos-related malignant pleural mesothelioma who was treated in a Phase I
      study with a granulocyte-macrophage colony-stimulating factor (GM-CSF)-expressing
      oncolytic adenovirus, Ad5/3-D24-GMCSF (ONCOS-102). The treatment resulted in
      prominent infiltration of CD8+ lymphocytes to tumor, marked induction of systemic
      antitumor CD8+ T-cells and induction of Th1-type polarization in the tumor. These
      results indicate that ONCOS-102 treatment sensitizes tumors to other
      immunotherapies by inducing a T-cell positive phenotype to an initially T-cell
      negative tumor.

PMID- 25941582
TI  - Unleashing antitumor T-cell activation without ensuing autoimmunity: the case for
      A20-deletion in adoptive CD8+ T-cell therapy.
AB  - Mechanisms controlling immune reactivity prevent excessive inflammation and
      autoimmunity, but generally dampen antitumor activity. We recently showed that
      adoptively transferred antitumor CD8+ T cells harboring a deletion of
      A20/Tnfaip3, a molecule controlling NF-kappaB activation, possessed heightened
      antitumor activity in vivo. The boosted immunity of A20-deleted CD8+ T cells
      correlated with a heightened capacity to produce IFNgamma and TNFalpha while
      expressing reduced levels of the immune checkpoint molecule PD-1.

PMID- 25941581
TI  - Chemoimmunotherapy targeting Wilms' tumor 1 (WT1)-specific cytotoxic T lymphocyte
      and helper T cell responses for patients with pancreatic cancer.
AB  - We designed a phase 1 study using dendritic cells (DCs) pulsed with a mixture of
      three types of Wilms' tumor 1 (WT1) peptides, including MHC class I/II restricted
      epitopes (DC/WT1-I/II). Our recent work reveals that the combination of DC/WT1
      I/II and chemotherapy induced long-term WT1-specific CD4+ and CD8+ T cell
      responses.

PMID- 25941578
TI  - Trial watch: IDO inhibitors in cancer therapy.
AB  - Indoleamine 2,3-dioxigenase 1 (IDO1) is the main enzyme that catalyzes the first,
      rate-limiting step of the so-called "kynurenine pathway", i.e., the metabolic
      cascade that converts the essential amino acid L-tryptophan (Trp) into L
      kynurenine (Kyn). IDO1, which is expressed constitutively by some tissues and in
      an inducible manner by specific subsets of antigen-presenting cells, has been
      shown to play a role in the establishment and maintenance of peripheral
      tolerance. At least in part, this reflects the capacity of IDO1 to restrict the
      microenvironmental availability of Trp and to favor the accumulation of Kyn and
      some of its derivatives. Also, several neoplastic lesions express IDO1, providing
      them with a means to evade anticancer immunosurveillance. This consideration has
      driven the development of several IDO1 inhibitors, some of which (including 1
      methyltryptophan) have nowadays entered clinical evaluation. In animal tumor
      models, the inhibition of IDO1 by chemical or genetic interventions is indeed
      associated with the (re)activation of therapeutically relevant anticancer immune
      responses. This said, several immunotherapeutic regimens exert robust clinical
      activity in spite of their ability to promote the expression of IDO1. Moreover, 1
      methyltryptophan has recently been shown to exert IDO1-independent
      immunostimulatory effects. Here, we summarize the preclinical and clinical
      studies testing the antineoplastic activity of IDO1-targeting interventions.

PMID- 25941583
TI  - Co-blockade of immune checkpoints and adenosine A2A receptor suppresses
      metastasis.
AB  - Immunosuppressive pathways active within the tumor microenvironment must be
      targeted in combination to sufficiently bolster antitumor immune defenses.
      Inhibition of A2A adenosine receptor signaling in combination with immune
      checkpoint blockade enhances CD8+ T and NK cell anti-metastatic activity. This
      results in reduced metastatic burden and improved survival in pre-clinical
      models.

PMID- 25941584
TI  - Alarmins released during local antitumor treatments play an essential role in
      enhancing tumor growth inhibition at treated and non-treated sites via a
      derivative of CCL3.
AB  - ECI301 (eMIP), a single amino-acid substituted CCL3 (MIP-1alpha), enhanced tumor
      growth inhibition and the abscopal effect (an effect distal to the target)
      following local antitumor therapy such as radiation, radiofrequency ablation
      (RFA), or hyperthermia treatment. The recent elucidation of the underlying
      mechanism may lead to a better antitumor therapy.

PMID- 25941585
TI  - Chemokine and lymph node homing receptor expression on pDC vary by graft source.
AB  - A randomized clinical trial of BM vs. blood stem cell transplants from unrelated
      donors showed that more plasmacytoid dendritic cells (pDCs) in BM grafts was
      associated with better post-transplant survival. Here, we describe differences in
      homing-receptor expression on pDC to explain observed differences following BM
      vs. blood stem cell transplantation.

PMID- 25941586
TI  - Dendritic cell-derived interleukin-15 is crucial for therapeutic cancer vaccine
      potency.
AB  - IL-15 supports improved antitumor immunity. How to best incorporate IL-15 into
      vaccine formulations for superior cancer immunotherapy remains a challenge. DC
      derived IL-15 (DCIL-15) notably has the capacity to activate DC, to substitute
      for CD4+ Th and to potentiate vaccine efficacy making IL-15-based therapies
      attractive treatment options. We observed in transplantable melanoma, glioma and
      metastatic breast carcinoma models that DCIL-15-based DNA vaccines in which DC
      specifically express IL-15 and simultaneously produce tumor Aghsp70 were able to
      mediate potent therapeutic efficacy that required both host Batf3+ DC and CD8+ T
      cells. In an inducible BrafV600E/Pten-driven murine melanoma model, DCIL-15 (not
      rIL-15)-based DNA vaccines elicited durable therapeutic CD8+ T cell-dependent
      antitumor immunity. DCIL-15 was found to be superior to rIL-15 in "licensing"
      both mouse and human DC, and for activating CD8+ T cells. Such activation
      occurred even in the presence of Treg, without a need for CD4+ Th, but was IL
      15/IL-15Ralpha-dependent. A single low-dose of DCIL-15 (not rIL-15)-based DC
      vaccines induced therapeutic antitumor immunity. CD14+ DC emigrating from human
      skin explants genetically-immunized by IL-15 and Aghsp70 were more effective than
      similar DC emigrating from the explants genetically-immunized by Aghsp70 in the
      presence of rIL-15 in expressing membrane-bound IL-15/IL-15Ralpha and activating
      CD8+ T cells. These results support future clinical use of DCIL-15 as a
      therapeutic agent in battling cancer.

PMID- 25941587
TI  - IGF-1R peptide vaccines/mimics inhibit the growth of BxPC3 and JIMT-1 cancer
      cells and exhibit synergistic antitumor effects with HER-1 and HER-2 peptides.
AB  - The insulin-like growth factor-1 receptor (IGF-1R) plays a crucial role in
      cellular growth, proliferation, transformation, and inhibition of apoptosis. A
      myriad of human cancer types have been shown to overexpress IGF-1R, including
      breast and pancreatic adenocarcinoma. IGF-1R signaling interferes with numerous
      receptor pathways, rendering tumor cells resistant to chemotherapy, anti-hormonal
      therapy, and epidermal growth factor receptor (EGFR, also known as HER-1) and v
      erb-b2 avian erythroblastic leukemia viral oncogene homolog 2, (ERBB2, best known
      as HER-2) -targeted therapies. Targeting the IGF:IGF-1R axis with innovative
      peptide inhibitors and vaccine antibodies thus represents a promising therapeutic
      strategy to overcome drug resistance and to provide new avenues for
      individualized and combinatorial treatment strategies. In this study, we
      designed, synthesized, and characterized several B-cell epitopes from the IGF
      1:IGF-1R axis. The chimeric peptide epitopes were highly immunogenic in outbred
      rabbits, eliciting high levels of peptide vaccine antibodies. The IGF-1R peptide
      antibodies and peptide mimics inhibited cell proliferation and receptor
      phosphorylation, induced apoptosis and antibody-dependent cellular cytotoxicity
      (ADCC), and significantly inhibited tumor growth in the transplantable BxPC-3
      pancreatic and JIMT-1 breast cancer models. Our results showed that the peptides
      and antibodies targeting residues 56-81 and 233-251 are potential therapeutic and
      vaccine candidates for the treatment of IGF-1R-expressing cancers, including
      those that are resistant to the HER-2-targeted antibody, trastuzumab.
      Additionally, we found additive antitumor effects for the combination treatment
      of the IGF-1R 56-81 epitope with HER-1-418 and HER-2-597 epitopes. Treatment with
      the IGF-1R/HER-1 or IGF-1R/HER-2 combination inhibited proliferation, invasion,
      and receptor phosphorylation, and induced apoptosis and ADCC, to a greater degree
      than single agents.

PMID- 25941589
TI  - Priming the pancreatic cancer tumor microenvironment for checkpoint-inhibitor
      immunotherapy.
AB  - Single agent immunotherapy is effective against several cancers, but has failed
      against poorly immunogenic cancers, including pancreatic cancer. Evaluation of
      pancreatic tumors following treatment with an experimental vaccine (Lutz et al.
      Cancer Immunology Research 2014) suggests that vaccination primes the tumor
      microenvironment (TME) for checkpoint-inhibitor immunotherapy, and supports a new
      platform for evaluating checkpoint-inhibitors in poorly immunogenic cancers.

PMID- 25941588
TI  - HER-3 peptide vaccines/mimics: Combined therapy with IGF-1R, HER-2, and HER-1
      peptides induces synergistic antitumor effects against breast and pancreatic
      cancer cells.
AB  - The human epidermal growth factor receptor 3 (HER-3/ErbB3) is a unique member of
      the human epidermal growth factor family of receptors, because it lacks intrinsic
      kinase activity and ability to heterodimerize with other members. HER-3 is
      frequently upregulated in cancers with epidermal growth factor receptor (EGFR/HER
      1/ErbB1) or human epidermal growth factor receptor 2 (HER-2/ErBB2)
      overexpression, and targeting HER-3 may provide a route for overcoming resistance
      to agents that target EGFR or HER-2. We have previously developed vaccines and
      peptide mimics for HER-1, HER-2 and vascular endothelial growth factor (VEGF). In
      this study, we extend our studies by identifying and evaluating novel HER-3
      peptide epitopes encompassing residues 99-122, 140-162, 237-269 and 461-479 of
      the HER-3 extracellular domain as putative B-cell epitopes for active
      immunotherapy against HER-3 positive cancers. We show that the HER-3 vaccine
      antibodies and HER-3 peptide mimics induced antitumor responses: inhibition of
      cancer cell proliferation, inhibition of receptor phosphorylation, induction of
      apoptosis and antibody dependent cellular cytotoxicity (ADCC). Two of the HER-3
      epitopes 237-269 (domain II) and 461-479 (domain III) significantly inhibited
      growth of xenografts originating from both pancreatic (BxPC3) and breast (JIMT-1)
      cancers. Combined therapy of HER-3 (461-471) epitope with HER-2 (266-296), HER-2
      (597-626), HER-1 (418-435) and insulin-like growth factor receptor type I (IGF
      1R) (56-81) vaccine antibodies and peptide mimics show enhanced antitumor effects
      in breast and pancreatic cancer cells. This study establishes the hypothesis that
      combination immunotherapy targeting different signal transduction pathways can
      provide effective antitumor immunity and long-term control of HER-1 and HER-2
      overexpressing cancers.

PMID- 25941590
TI  - Differential potency of regulatory T cell-mediated immunosuppression in kidney
      tumors compared to subcutaneous tumors.
AB  - In many cancers, regulatory T cells (Treg) play a crucial role in suppressing the
      effector immune response thereby permitting tumor development. Indeed, in mouse
      models, their depletion can promote the regression of tumors of various origins,
      including renal cell carcinoma when located subcutaneous (SC). In the present
      study, we aimed to assess the importance of Treg immunosuppression in the
      physiologic context of metastatic renal carcinoma (Renca) disease. To that
      purpose we inoculated renal tumors orthotopically, intra-kidney (IK), in mice.
      Treg depletions were performed using anti-CD4 antibody in wild type mice or
      diphtheria toxin (DT) in Foxp3DTR transgenic mice. Our main observation was that
      Treg were not the key immunosuppressive component of the IK tumoral
      microenvironment, compared to the same tumors located SC. We demonstrated that
      the CD8+ effector immune response was still suppressed in IK tumors when compared
      to SC tumors, following Treg depletion. Furthermore, the level of program cell
      death protein (PD)-1 was increased on the surface of CD4+ T cells infiltrating IK
      tumors compared to SC tumors. Finally, the Treg-independent immunosuppression,
      occurring in IK tumors, was potent enough to inhibit regression of concomitant SC
      tumors, normally responsive to Treg depletion. Our findings provide further
      insight into the immunosuppressive nature of the immune response generated in the
      kidney microenvironment, suggesting that it can have additional mechanisms in
      addition to Treg. These observations might help to identify better targets from
      the kidney tumor microenvironment for future cancer therapies.

PMID- 25941591
TI  - A pilot Phase I study combining peptide-based vaccination and NGR-hTNF vessel
      targeting therapy in metastatic melanoma.
AB  - Administration of NGR-TNF, a tumor vessel-targeting and tumor necrosis factor
      alpha TNFalpha) peptide conjugate, with immunotherapy has been shown to inhibit
      tumor growth in mice. Thus, we planned a Phase I pilot clinical trial to assess
      safety, immune and clinical response of this combination treatment for advanced
      melanoma. NA17.A2 and MAGE-3.A1 peptides were used as vaccine. HLA-A*0201 or HLA
      A*01 metastatic melanoma patients received human NGR-hTNF i.v. alternating with
      s.c. weekly injections of either of the peptides emulsified in Montanide. The T
      cell response was assessed ex-vivo using peripheral blood mononuclear cells
      (PBMCs) before, during and after therapy. The serum level of chromogranin A
      (CgA), soluble TNF receptors (sTNFR1/2), vascular endothelial growth factor
      (VEGF), and MIP-1beta and MCP-1 chemokines, was determined. In 3 subjects, pre-
      and post-treatment tumor lesions were examined by immunohistochemistry.
      Clinically, chills were observed in 4 patients during NGR-hTNF infusion and
      erythema at vaccination site was seen in 7 patients. T-cell response against the
      vaccine or against other melanoma-associated antigens was detectable after
      treatment in 6 out of 7 tested patients. Low level or reduction of CgA and sTNFR
      and increase of MIP-1beta and MCP-1 were found in patients sera. In the lesions
      examined the immune infiltrate was scanty but macrophage number increased in post
      therapy lesions. From a clinical standpoint, a long term survival (>4 months) was
      found in 6 out of 8 evaluable patients (4, 4, 7, 11, 23+, 25+, 25+, 29+ months).
      The combination of NGR-hTNF and vaccine in metastatic melanoma patients was well
      tolerated, often associated with an ex-vivo T cell response and long-term overall
      survival. These findings warrant confirmation in a larger group of patients.

PMID- 25941592
TI  - Immunotherapy of metastatic and autochthonous liver cancer with IL-15/IL-15Ralpha
      fusion protein.
AB  - Liver cancer has a poor prognosis. Our recent study demonstrates that hyper-IL
      15, composed of IL-15 and the sushi domain of IL-15 receptor alpha chain,
      provides an effective therapy against well-established metastatic and
      autochthonous liver cancers in mouse models by triggering activation and
      expansion of hepatic CD8+ T cells.

PMID- 25941594
TI  - Cracking the glioma-NK inhibitory code: toward successful innate immunotherapy.
AB  - Natural killer (NK) cells eradicate galectin-deficient malignant gliomas without
      the necessity for T cell cooperation. This phenomenon was discovered as a
      consequence of reducing glioma-derived galectin-1. We propose that stimulation of
      endogenous antitumor NK cell activity may be achieved by reducing potent tumor
      derived NK cell inhibitors, such as galectin-1, and that such agents be tested in
      the clinic to treatbrain tumors.

PMID- 25941595
TI  - The tumor immune microenvironment in octogenarians with stage I non-small cell
      lung cancer.
AB  - Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related
      mortality and has increasingly become a disease of elderly patients. Elderly
      patients are underrepresented in clinical trials that evaluate treatments for
      NSCLC. It has been suggested that patients >65 years of age have less robust
      immune responses to infections, immunizations, and tumors compared with younger
      patients. With increasing focus and number of immunotherapy clinical trials for
      NSCLC, we investigated the relationship between patient age and the tumor immune
      microenvironment in NSCLC. Using tissue microarrays from 1,278 patients with
      surgically resected Stage I NSCLC (<=65 years [33%], 66-79 years [55%], and >=80
      years [12%]), we determined whether quantitative and qualitative immune cell
      infiltration in the tumor differed between younger and older patients.
      Furthermore, we investigated the prognostic value of immune cell infiltration
      with respect to recurrence in octogenarians. We found that there were no
      statistically significant differences between older and younger patients in
      tumoral immune infiltration or effector regulatory immune response ratios
      (FoxP3/CD3, FoxP3/CD4, and FoxP3/CD8 ratios). In octogenarians, presence of low
      tumoral CD68+ immune cells was an independent predictor of recurrence. In the
      uniform cohort of surgically selected and resected Stage I NSCLC patients, tumor
      immune cell infiltration among the older age group resembled other age groups.
      Our study provides information that supports inclusion of older age patients
      selected for surgical resection in neoadjuvant or adjuvant immunotherapy clinical
      trials for lung cancer.

PMID- 25941596
TI  - Lymphocyte activation gene-3 (LAG-3, CD223) in plasmacytoid dendritic cells
      (pDCs): a molecular target for the restoration of active antitumor immunity.
AB  - We have recently reported that lymphocyte activation gene-3 (LAG-3,CD223)
      mediates the alternative, IFNalpha-deficient activation of plasmacytoid dendritic
      cells (pDCs) at tumor sites. Our findings define a novel tumor-driven strategy
      that promotes immunosuppression by pDCs, and we have provided more detailed
      information regarding the immunomodulatory role of of LAG-3. The translational
      relevance of our results for the treatment of tumors and autoimmune diseases is
      discussed herein.

PMID- 25941597
TI  - Novel immune checkpoint blocker approved for the treatment of advanced melanoma.

PMID- 25941599
TI  - Chimeric antigen receptor T cells are vulnerable to immunosuppressive mechanisms
      present within the tumor microenvironment.
AB  - Chimeric antigen receptor (CAR) modified T cells have shown early promise in
      hematological malignancies. However, in solid malignancies CAR T cells must
      overcome a distinct immunosuppressive microenvironment which may compromise their
      capacity to mediate antitumor activity.

PMID- 25941598
TI  - Ectopic expression of embryonic stem cell and other developmental genes in
      cutaneous T-cell lymphoma.
AB  - Cutaneous T-cell lymphoma (CTCL) is a potentially devastating malignancy. The
      pathogenesis of this cancer remains poorly elucidated. Previous studies focused
      on analysis of expression and function of known oncogenes and tumor suppressor
      genes. However, emerging reports highlight that it is also important to analyze
      the expression of genes that are ectopically expressed in CTCL (e.g., embryonic
      stem cell genes (ESC), cancer testis (CT) genes, etc.). Currently, it is not
      known whether ESC genes are expressed in CTCL. In the current work, we analyze by
      RT-PCR the expression of 26 ESC genes, many of which are known to regulate
      pluripotency and promote cancer stem cell-like phenotype, in a historic cohort of
      60 patients from Boston and in a panel of 11 patient-derived CTCL cell lines and
      compare such expression to benign inflammatory dermatoses that often clinically
      mimic CTCL. Our findings document that many critical ESC genes including NANOG,
      SOX2, OCT4 (POU5F1) and their upstream and downstream signaling members are
      expressed in CTCL. Similarly, polycomb repressive complex 2 (PRC2) genes (i.e.,
      EZH2, EED, and SUZ12) are also expressed in CTCL lesional skin. Furthermore,
      select ESC genes (OCT4, EED, TCF3, THAP11, CHD7, TIP60, TRIM28) are
      preferentially expressed in CTCL samples when compared to benign skin biopsies.
      Our work suggests that ESC genes are ectopically expressed together with CT
      genes, thymocyte development genes and B cell-specific genes and may be working
      in concert to promote tumorigenesis. Specifically, while ESC genes may be
      promoting cancer stem cell-like phenotype, CT genes may be contributing to
      aneuploidy and genomic instability by producing aberrant chromosomal
      translocations. Further analysis of ESC expression and function in this cancer
      will greatly enhance our fundamental understanding of CTCL and will help us
      identify novel therapeutic targets.

PMID- 25941593
TI  - Trial watch: Dendritic cell-based anticancer therapy.
AB  - The use of patient-derived dendritic cells (DCs) as a means to elicit
      therapeutically relevant immune responses in cancer patients has been extensively
      investigated throughout the past decade. In this context, DCs are generally
      expanded, exposed to autologous tumor cell lysates or loaded with specific tumor
      associated antigens (TAAs), and then reintroduced into patients, often in
      combination with one or more immunostimulatory agents. As an alternative, TAAs
      are targeted to DCs in vivo by means of monoclonal antibodies, carbohydrate
      moieties or viral vectors specific for DC receptors. All these approaches have
      been shown to (re)activate tumor-specific immune responses in mice, often
      mediating robust therapeutic effects. In 2010, the first DC-based preparation
      (sipuleucel-T, also known as Provenge(r)) has been approved by the US Food and
      Drug Administration (FDA) for use in humans. Reflecting the central position
      occupied by DCs in the regulation of immunological tolerance and adaptive
      immunity, the interest in harnessing them for the development of novel
      immunotherapeutic anticancer regimens remains high. Here, we summarize recent
      advances in the preclinical and clinical development of DC-based anticancer
      therapeutics.

PMID- 25941600
TI  - Antibody response to cancer/testis (CT) antigens: A prognostic marker in cancer
      patients.
AB  - Immune responses to tumor antigens have been reported in cancer patients.
      However, the relevance of such spontaneous immune responses to the clinical
      course has not been studied extensively. We showed that the overall survival of
      patients with antibodies against NY-ESO-1 or XAGE1 (GAGED2a) antigen was
      prolonged in gastric or lung cancer patients, respectively.

PMID- 25941601
TI  - Heteroclitic XBP1 peptides evoke tumor-specific memory cytotoxic T lymphocytes
      against breast cancer, colon cancer, and pancreatic cancer cells.
AB  - XBP1 is a critical transcriptional activator of the unfolded protein response
      (UPR), which increases tumor cell survival under prolonged endoplasmic reticulum
      (ER) stress and hypoxic conditions.This study was designed to evaluate the
      immunogenicity of heteroclitic XBP1 unspliced (US)184-192 (YISPWILAV) and
      heteroclictic XBP1 spliced (SP)367-375 (YLFPQLISV) HLA-A2 peptides, and to
      characterize the specific activities of XBP1 peptides-specific cytotoxic T
      lymphocytes (XBP1-CTL) against breast cancer, colon cancer, and pancreatic cancer
      cells.The XBP1-CTL had upregulated expression of critical T cell markers and
      displayed HLA-A2-restricted and antigen-specific activities against breast
      cancer, colon cancer and pancreatic cancer cells. XBP1-CTL were enriched
      withCD45RO+ memory CTL, which showed high expression of critical T cell markers
      (CD28, ICOS, CD69, CD40L), cell proliferation and antitumor activities as
      compared to CD45RO- non-memory CTL. The effector memory (EM: CD45RO+CCR7-) subset
      had the highest level of cell proliferation while the central memory (CM:
      CD45RO+CCR7+) subset demonstrated enhanced functional activities (CD107a
      degranulation, IFNgamma/IL-2 production) upon recognition of the respective tumor
      cells. Furthermore, both the EM and CM XBP1-CTL subsets expressed high levels of
      Th1 transcription regulators Tbet and Eomes. The highest frequencies of IFNgamma
      or granzyme B producing cells were detected within CM XBP1-CTL subset that were
      either Tbet+ or Eomes+ in responding to the tumor cells.These results demonstrate
      the immunotherapeutic potential of a cocktail of immunogenic HLA-A2 specific
      heteroclitic XBP1 US184-192 and heteroclictic XBP1 SP367-375 peptides to induce
      CD3+CD8+ CTL enriched for CM and EM cells with specific antitumor activities
      against a variety of solid tumors.

PMID- 25941603
TI  - Tumor-infiltrating T-cells: important players in clinical outcome of advanced
      melanoma patients.
AB  - Immune escape mechanisms are prevalent in tumors, while their influence on the
      potency of antitumor immunotherapy has yet to be distinguished. We recently
      showed that increased numbers of intratumoral T cells rather than immune-escape
      mechanisms significantly correlated with clinical outcome of advanced melanoma
      patients to subsequent autologous tumor cell vaccination. Our data emphasize the
      therapeutic relevance of tumor-infiltrating T cells for the clinical outcome.

PMID- 25941602
TI  - Sperm associated antigen 9 (SPAG9) expression and humoral response in benign and
      malignant salivary gland tumors.
AB  - Salivary gland cancers are highly aggressive epithelial tumor associated with
      metastatic potential and high mortality. The tumors are biologically diverse and
      are of various histotypes. Besides, the detection and diagnosis is a major
      problem of salivary gland cancer for available treatment modalities. In the
      present study, we have investigated the association of sperm associated antigen 9
      (SPAG9) expression with salivary gland tumor (SGT). Clinical specimens of benign
      (n = 16) and malignant tumors (n = 86) were examined for the SPAG9 expression. In
      addition, the sera and adjacent non-cancerous tissues (n = 72) from available
      patients were obtained. Our in situ RNA hybridization and immunohistochemistry
      (IHC) analysis revealed significant difference (p = 0.0001) in SPAG9 gene and
      protein expression in benign (63%) and malignant tumor (84%) specimens. Further,
      significant association was also observed between SPAG9 expression and malignant
      tumors (P = 0.05). A cut-off value of >10% cells expressing SPAG9 protein
      designated as positive in IHC, predicted presence of malignant SGT with 83.72%
      sensitivity, 100% specificity, 100% PPV and 83.72% NPV. Humoral response against
      SPAG9 protein was generated in 68% of SGT patients. A cut-off value of 0.212 OD
      for anti-SPAG9 antibodies in ELISA predicted presence of malignant SGT with
      69.23% sensitivity, 100% specificity, 100% PPV and 78.94% NPV. Collectively, our
      data suggests that the majority of SGT show significant difference and
      association among benign and malignant tumors for SPAG9 gene and protein
      expression and also exhibit humoral response against SPAG9 protein. Hence, SPAG9
      may be developed as a biomarker for detection and diagnosis of salivary gland
      tumors.

PMID- 25941604
TI  - Tumor-associated antigen specific CD8+ T cells in hepatocellular carcinoma - a
      promising target for immunotherapy.
AB  - Immunotherapy is a promising treatment option for patients with hepatocellular
      carcinoma (HCC). Indeed, CD8+ T-cell responses against various tumor antigens
      occur in these patients. However, these antitumoral T cells show a severely
      impaired effector function. Several immunosuppressive mechanisms contribute to
      this T-cell failure, including regulatory T cells and inhibitory receptors.

PMID- 25941605
TI  - Using alpha radiation to boost cancer immunity?
AB  - Radioimmunotherapy aims to deliver radiation directly to cancer cells by means of
      a tumor specific vector coupled to a radionuclide. Alpha radionuclides are very
      potent agents to treat disseminated cancer and metastasis. We have demonstrated
      that alpha radiation can also induce immunogenic cell death, reinforcing interest
      in their clinical development.

PMID- 25941607
TI  - Limitations of bystander killing in Th1/M1 immune responses against a secreted
      tumor antigen.
AB  - T-cell recognition of tumor antigens presented on tumor-infiltrating macrophages
      (TAMs) induces a tumoricidal M1-like phenotype. Resultant indirect immune
      responses could eliminate not only antigen secreting (AgPOS), but also antigen
      negative (AgNEG) tumor cells via bystander killing. Such broad-spectrum response
      could eliminate antigenically heterogeneous tumors. Using an in vivo model of
      CD4+ T-cell mediated immunity against MHC II negative myeloma cells, bystander
      killing of AgNEG cells was ineffective due to strict spatial constraints of Th1
      induced TAM cytotoxicity.

PMID- 25941608
TI  - Evidence of synergy with combined BRAF-targeted therapy and immune checkpoint
      blockade for metastatic melanoma.
AB  - Significant advances in the treatment of melanoma have been made with BRAF
      targeted therapy and immune checkpoint blockade, and these strategies are now
      being combined empirically in clinical trials. Potential synergy is demonstrated
      in murine models and in analysis of longitudinal biopsies from patients on trial,
      however important questions remain regarding toxicity, optimal timing and
      sequence of therapy.

PMID- 25941609
TI  - New insights into androgenic immune regulation.
AB  - Androgens negatively affect both central and peripheral immunity. Their potent
      immunosuppressive ability is thought to lead to gender dimorphism in autoimmune
      and infectious disease and hamper immunosurveillance of tumors. Therefore, we
      investigated the molecular underpinnings of androgens suppression of T-cell
      differentiation and found evidence that developing strategies to counteract these
      inhibitory effects may foster successful cancer immunotherapy in the future.

PMID- 25941610
TI  - Th1 epitope selection for clinically effective cancer vaccines.
AB  - New cancer immunotherapies mark progress in our understanding of tumor biology
      and harnessing the immune system's management of self. However, protein- and
      peptide-based vaccines are not yet consistently efficacious. Recent work uncovers
      principles governing the genesis of T helper type-restrictive immunity to self
      antigens elicited by vaccine epitopes, enabling vaccines to skew the balance from
      tolerogenic Type II (Th2) to inflammatory Type I (Th1) T cells, and invigorating
      this cancer immunotherapeutic approach.

PMID- 25941611
TI  - Tumor stroma-derived factors skew monocyte to dendritic cell differentiation
      toward a suppressive CD14+ PD-L1+ phenotype in prostate cancer.
AB  - Tumor-associated stromal myofibroblasts are essential for the progression and
      metastatic spread of solid tumors. Corresponding myeloid cell infiltration into
      primary tumors is a negative prognostic factor in some malignancies. The aim of
      this study was to define the exact role of stromal myofibroblasts and stromal
      factors in early prostate carcinoma (PCa) regulating monocyte infiltration and
      differentiation into dendritic cells (DCs). Epithelial and stromal primary
      cultures were generated from PCa biopsies and their purity confirmed. Stromal
      cells produced significantly more of the (C-C) motif chemokine ligand 2 (CCL2),
      interleukin 6 (IL-6) and transforming growth factor beta (TGFbeta) than
      epithelial cells. Monocyte chemoattraction was predominantly due to stromal
      derived factors, mainly CCL2. DCs generated in the presence of stromal (but not
      epithelial) factors upregulated CD209, but failed to downregulate the monocyte
      marker CD14 in a signal transducer and activator of transcription 3 (STAT3)
      dependent manner. Monocytes exposed to stromal factors did not produce detectable
      amounts of IL-10, however, upon lipopolysaccharide stimulation, stromal factor
      generated dendritic cells (sDC) produced significantly more IL-10 and less IL-12
      than their conventional DC counterparts. sDC failed to cross-present tumor
      antigen to CD8+ T cells and suppressed T-cell proliferation. Most importantly,
      sDC expressed significantly elevated levels of programmed cell death ligand-1 (PD
      L1) in a primarily STAT3 and IL-6-dependent manner. In parallel with our findings
      in vitro, tumor-infiltrating CD14+ cells in situ were found to express both PD-L1
      and CD209, and a higher percentage of tumor-associated CD3+ T cells expressed
      programmed cell death-1 (PD-1) molecules compared to T cells in blood. These
      results demonstrate a hitherto undescribed, fundamental contribution of tumor
      associated stromal myofibroblasts to the development of an immunosuppressive
      microenvironment in early PCa.

PMID- 25941606
TI  - Trial Watch: Radioimmunotherapy for oncological indications.
AB  - During the past two decades, it has become increasingly clear that the
      antineoplastic effects of radiation therapy do not simply reflect the ability of
      X-, beta- and gamma-rays to damage transformed cells and directly cause their
      permanent proliferative arrest or demise, but also involve cancer cell-extrinsic
      mechanisms. Indeed, among other activities, radiotherapy has been shown to favor
      the establishment of tumor-specific immune responses that operate systemically,
      underpinning the so-called 'out-of-field' or 'abscopal' effect. Thus, ionizing
      rays appear to elicit immunogenic cell death, a functionally peculiar variant of
      apoptosis associated with the emission of a particularly immunostimulatory
      combination of damage-associated molecular patterns. In line with this notion,
      radiation therapy fosters, and thus exacerbates, the antineoplastic effects of
      various treatment modalities, including surgery, chemotherapy and various
      immunotherapeutic agents. Here, we summarize recent advances in the use of
      ionizing rays as a means to induce or potentiate therapeutically relevant
      anticancer immune responses. In addition, we present clinical trials initiated
      during the past 12 months to test the actual benefit of radioimmunotherapy in
      cancer patients.

PMID- 25941613
TI  - The ontogeny of tumor-associated macrophages: a new understanding of cancer
      elicited inflammation.
AB  - Clinical and experimental models have identified macrophages as potential targets
      for cancer therapy, however, the nature of macrophage differentiation and
      function in the context of malignant disease remain largely uncharacterized. This
      commentary provides the author's perspective on the recently published article
      "The cellular and molecular origin of tumor-associated macrophages," which
      demonstrated that tumor growth elicits a specific macrophage differentiation
      pathway.

PMID- 25941612
TI  - Vgamma9Vdelta2-T cells as antigen presenting cells for iNKT cell based cancer
      immunotherapy.
AB  - CD1d-restricted invariant natural killer T cells (iNKT) constitute an important
      immunoregulatory T-cell subset involved in the induction of antitumor immune
      responses. Here, we provide a view on the recent observation that Vgamma9Vdelta2
      T cells, through trogocytosis of CD1d-containing membrane fragments, have the
      capacity to act as antigen presenting cells for iNKT.

PMID- 25941614
TI  - Intraperitoneal oxidative stress as an oncolytic immunomodulator?
AB  - Intraperitoneal oxidative stress effectively converts the immune response against
      the papillomavirus-associated rabbit VX2 carcinoma from tumor permissive to
      tumoricidal and leads to a sustainable oncolytic immune response that can be
      adoptively transferred.

PMID- 25941615
TI  - Targeting tumor-associated macrophages in cancer therapy and understanding their
      complexity.
AB  - Macrophage infiltration has been identified as an independent, poor prognostic
      factor for patients afflicted with various cancer entities. However, the
      characterization of tumor-associated macrophages (TAMs) prior to and following
      cancer patient treatment has been limited. Our study analyzed tumor biopsies
      before and after anti-CSF-1R antibody treatment unraveling the nature of TAMs and
      providing novel insights into their phenotypic and functional characteristics in
      cancer.

PMID- 25941616
TI  - Lessons from immunology: IL4R directly promotes mammary tumor metastasis.
AB  - Interleukin-4 (IL4), a Th2 cytokine, signals through IL4 receptors (IL4Rs) to
      regulate increased lymphocyte proliferation and survival. We have recently
      discovered that IL4 also promotes these phenotypes in mammary cancer cells
      expressing IL4Rs to enhance their metastatic ability. Targeting IL4/IL4R
      signaling on cancer cells themselves may limit metastatic disease.

PMID- 25941617
TI  - STAT1-S727 - the license to kill.
AB  - Serine phosphorylation has generally been considered indispensable for full
      transcriptional activity of STAT proteins. Recent data indicate that CDK8
      mediated phosphorylation of signal transducer and activator of transcription 1
      (STAT1) on S727 inhibits natural killer (NK) cell cytotoxicity and restrains
      tumor surveillance. These findings implicate CDK8 as a promising target for
      immunotherapy.

PMID- 25941618
TI  - Tumor antigen-targeting monoclonal antibody-based immunotherapy: Orchestrating
      combined strategies for the development of long-term antitumor immunity.
AB  - Tumor antigen (TA)-targeting monoclonal antibody (mAb)-based treatments are
      considered to be one of the most successful strategies in cancer therapy. Besides
      targeting TAs and inducing tumor cell death, such antibodies interact with immune
      cells through Fc-dependent mechanisms to induce adaptive memory immune responses.
      However, multiple inhibitory/immunosuppressive pathways can be induced by tumor
      cells to limit the establishment of an efficient antitumor response and
      consequently a sustained clinical response to TA-targeting mAbs. Here, we provide
      an overview on how TA-targeting mAbs in combination with conventional cancer
      therapies and/or inhibitors of key immunosuppressive pathways might represent
      promising approaches to achieve long-term tumor control.

PMID- 25941619
TI  - Vitamin B6 improves the immunogenicity of cisplatin-induced cell death.
AB  - We have recently demonstrated that pyridoxine, a precursor of vitamin B6,
      increases the immunogenicity of non-small cell lung carcinoma (NSCLC) cells
      succumbing to cisplatin (cis-diamminedichloroplatinum(II), CDDP). Accordingly,
      pyridoxine promoted the antineoplastic activity of CDDP in NSCLC-bearing mice
      only in the presence of an intact immune system. These findings may have
      implications for the development of novel strategies to circumvent CDDP
      resistance.

PMID- 25941620
TI  - Induction of immunogenic cell death by targeting RIG-I-like helicases in
      pancreatic cancer.
AB  - RIG-I-like helicases (RLH) are cytosolic sensors for viral RNA inducing type I
      interferon production. We found that pancreatic cancer cells express functional
      RLH and are susceptible to RLH-induced apoptosis via intrinsic and extrinsic
      pathways. Tumor cells displayed features of immunogenic cell death resulting in
      dendritic cell activation, enhanced antigen cross-presentation and efficient
      tumor control in vivo.

PMID- 25941622
TI  - The therapeutic efficacy of the oncolytic virus Delta24-RGD in a murine glioma
      model depends primarily on antitumor immunity.
AB  - Oncolytic viruses selectively lyse tumor cells, making these agents a promising
      treatment modality for glioma. Accumulating data suggest that the immune system
      plays an important role in the anti-glioma activity of oncolytic viruses. In an
      immune competent glioma model, the therapeutic effect of the oncolytic adenovirus
      Delta24-RGD was found to depend primarily on antitumor immune responses.

PMID- 25941623
TI  - A single mutation in the gatekeeper residue in TgMAPKL-1 restores the inhibitory
      effect of a bumped kinase inhibitor on the cell cycle.
AB  - Toxoplasma gondii is the causative pathogen for Toxoplasmosis. Bumped kinase
      inhibitor 1NM-PP1 inhibits the growth of T. gondii by targeting TgCDPK1. However,
      we recently reported that resistance to 1NM-PP1 can be acquired via a mutation in
      T. gondii mitogen-activated protein kinase like 1 (TgMAPKL-1). Further
      characterization of how this TgMAPKL-1 mutation restores the inhibitory effect of
      1NM-PP1 would shed further light on the function of TgMAPKL-1 in the parasite
      life cycle. Therefore, we made parasite clones with TgMAPKL-1 mutated at the
      gatekeeper residue Ser 191, which is critical for 1NM-PP1 susceptibility. Host
      cell lysis of RH/ku80(-)/HA-TgMAPKL-1(S191A) was completely inhibited at 250 nM
      1NM-PP1, whereas that of RH/ku80(-)/HA-TgMAPKL-1(S191Y) was not. By comparing 1NM
      PP1-sensitive (RH/ku80(-)/HA-TgMAPKL-1(S191A)) and -resistant (RH/ku80(-)/HA
      TgMAPKL-1(S191Y)) clones, we observed that inhibition of TgMAPKL-1 blocked cell
      cycle progression after DNA duplication. Morphological analysis revealed that
      TgMAPKL-1 inhibition caused enlarged parasite cells with many daughter cell
      scaffolds and imcomplete cytokinesis. We conclude that the mutation in TgMAPKL-1
      restored the cell cycle-arresting effect of 1NM-PP1 on T. gondii endodyogeny.
      Given that endodyogeny is the primary mechanism of cell division for both the
      tachyzoite and bradyzoite stages of this parasite, TgMAPKL-1 may be a promising
      target for drug development. Exploration of the signals that regulate TgMAPKL-1
      will provide further insights into the unique mode of T. gondii cell division. 

PMID- 25941625
TI  - Evidence for reversion towards anthelmintic susceptibility in Teladorsagia
      circumcincta in response to resistance management programmes.
AB  - Maintaining production and economic viability in the face of resistance to
      multiple anthelmintic actives is a challenge for farmers in many countries. In
      this situation, most farmers in New Zealand rely on the use of combination
      products, containing multiple actives with similar spectra of activity, in order
      to maintain control. However, there are concerns that use of combinations, once
      resistance has already developed to the individual actives, could rapidly lead to
      complete failure of all actives. This study followed seven farms, previously
      diagnosed with resistance to at least two classes of anthelmintic, which were
      implementing a tailored programme of 'best practice parasite management'. The aim
      was to ascertain whether the programmes, which included the almost exclusive use
      of combination anthelmintics, were able to prevent resistance from developing
      further. Strategies implemented on each farm varied, but had consistent
      underlying principles i.e. to avoid over-use of anthelmintics; to minimise
      parasite challenge to susceptible stock; to maintain refugia of susceptibility
      and to ensure that only effective anthelmintics were used. Annual faecal egg
      count reduction tests (FECRT) were undertaken in lambs on all farms to monitor
      anthelmintic efficacy over 5 years. The efficacy of albendazole, ivermectin and
      levamisole was calculated and the changes in efficacy against Teladorsagia
      circumcincta assessed. Overall, there was a significant improvement in the
      effectiveness of both levamisole and ivermectin against T. circumcincta, and a
      positive but non-significant trend in efficacy of albendazole, i.e. there was
      evidence for reversion towards susceptibility. Hence, the almost exclusive use of
      combination anthelmintics, integrated with other resistance management
      strategies, did not result in further resistance development despite all farms
      exhibiting resistance to multiple actives at the outset. What-is-more, the
      measured increases in anthelmintic efficacy suggests that adoption of best
      practice management strategies may extend the useful life of anthelmintics even
      after resistance has been diagnosed. 

PMID- 25941624
TI  - Drug resistance analysis by next generation sequencing in Leishmania.
AB  - The use of next generation sequencing has the power to expedite the
      identification of drug resistance determinants and biomarkers and was applied
      successfully to drug resistance studies in Leishmania. This allowed the
      identification of modulation in gene expression, gene dosage alterations, changes
      in chromosome copy numbers and single nucleotide polymorphisms that correlated
      with resistance in Leishmania strains derived from the laboratory and from the
      field. An impressive heterogeneity at the population level was also observed,
      individual clones within populations often differing in both genotypes and
      phenotypes, hence complicating the elucidation of resistance mechanisms. This
      review summarizes the most recent highlights that whole genome sequencing brought
      to our understanding of Leishmania drug resistance and likely new directions. 

PMID- 25941627
TI  - The AhR agonist VAF347 augments retinoic acid-induced differentiation in leukemia
      cells.
AB  - In binary cell-fate decisions, driving one lineage and suppressing the other are
      conjoined. We have previously reported that aryl hydrocarbon receptor (AhR)
      promotes retinoic acid (RA)-induced granulocytic differentiation of lineage
      bipotent HL-60 myeloblastic leukemia cells. VAF347, an AhR agonist, impairs the
      development of CD14(+)CD11b(+) monocytes from granulo-monocytic (GM) stage
      precursors. We thus hypothesized that VAF347 propels RA-induced granulocytic
      differentiation and impairs D3-induced monocytic differentiation of HL-60 cells.
      Our results show that VAF347 enhanced RA-induced cell cycle arrest, CD11b
      integrin expression and neutrophil respiratory burst. Granulocytic
      differentiation is known to be driven by MAPK signaling events regulated by Fgr
      and Lyn Src-family kinases, the CD38 cell membrane receptor, the Vav1 GEF, the c
      Cbl adaptor, as well as AhR, all of which are embodied in a putative signalsome.
      We found that the VAF347 AhR ligand regulates the signalsome. VAF347 augments RA
      induced expression of AhR, Lyn, Vav1, and c-Cbl as well as p47(phox). Several
      interactions of partners in the signalsome appear to be enhanced: Fgr interaction
      with c-Cbl, CD38, and with pS259c-Raf and AhR interaction with c-Cbl and Lyn.
      Thus, we report that, while VAF347 impedes monocytic differentiation induced by
      1,25-dihydroxyvitamin D3, VAF347 promotes RA-induced differentiation. This effect
      seems to involve but not to be limited to Lyn, Vav1, c-Cbl, AhR, and Fgr. 

PMID- 25941626
TI  - Buparvaquone is active against Neospora caninum in vitro and in experimentally
      infected mice.
AB  - The naphthoquinone buparvaquone is currently the only drug used against
      theileriosis. Here, the effects of buparvaquone were investigated in vitro and in
      an experimental mouse model for Neospora caninum infection. In 4-day
      proliferation assays, buparvaquone efficiently inhibited N. caninum tachyzoite
      replication (IC50 = 4.9 nM; IC100 = 100 nM). However, in the long term
      tachyzoites adapted and resumed proliferation in the presence of 100 nM
      buparvaquone after 20 days of cultivation. Parasiticidal activity was noted after
      9 days of culture in 0.5 uM or 6 days in 1 uM buparvaquone. TEM of N. caninum
      infected fibroblasts treated with 1 uM buparvaquone showed that the drug acted
      rather slowly, and ultrastructural changes were evident only after 3-5 days of
      treatment, including severe alterations in the parasite cytoplasm, changes in the
      composition of the parasitophorous vacuole matrix and a diminished integrity of
      the vacuole membrane. Treatment of N. caninum infected mice with buparvaquone
      (100 mg/kg) either by intraperitoneal injection or gavage prevented neosporosis
      symptoms in 4 out of 6 mice in the intraperitoneally treated group, and in 6 out
      of 7 mice in the group receiving oral treatment. In the corresponding controls,
      all 6 mice injected intraperitoneally with corn oil alone died of acute
      neosporosis, and 4 out of 6 mice died in the orally treated control group.
      Assessment of infection intensities in the treatment groups showed that, compared
      to the drug treated groups, the controls showed a significantly higher parasite
      load in the lungs while cerebral parasite load was higher in the buparvaquone
      treated groups. Thus, although buparvaquone did not eliminate the parasites
      infecting the CNS, the drug represents an interesting lead with the potential to
      eliminate, or at least diminish, fetal infection during pregnancy. 

PMID- 25941628
TI  - 4-Oxo-(E)-2-hexenal produced by Heteroptera induces permanent locomotive
      impairment in crickets that correlates with free thiol depletion.
AB  - Heteropterans produce 2-alkenals and 4-keto-2-alkenals that function as defense
      substances or pheromones. However, in spite of advances in heteropteran
      chemistry, it is still unclear how these compounds affect insect physiology. We
      found that exposure to 4-oxo-(E)-2-hexenal (OHE) induced permanent paralysis and
      death in crickets, an experimental model. The depletion of free thiols in leg
      tissues of OHE-treated crickets and the in vitro adduct formation of OHE with a
      thiol compound suggest that covalent binding of OHE to biologically active thiols
      is a potential cause affecting crickets' locomotion. 

PMID- 25941621
TI  - Consensus guidelines for the detection of immunogenic cell death.
AB  - Apoptotic cells have long been considered as intrinsically tolerogenic or unable
      to elicit immune responses specific for dead cell-associated antigens. However,
      multiple stimuli can trigger a functionally peculiar type of apoptotic demise
      that does not go unnoticed by the adaptive arm of the immune system, which we
      named "immunogenic cell death" (ICD). ICD is preceded or accompanied by the
      emission of a series of immunostimulatory damage-associated molecular patterns
      (DAMPs) in a precise spatiotemporal configuration. Several anticancer agents that
      have been successfully employed in the clinic for decades, including various
      chemotherapeutics and radiotherapy, can elicit ICD. Moreover, defects in the
      components that underlie the capacity of the immune system to perceive cell death
      as immunogenic negatively influence disease outcome among cancer patients treated
      with ICD inducers. Thus, ICD has profound clinical and therapeutic implications.
      Unfortunately, the gold-standard approach to detect ICD relies on vaccination
      experiments involving immunocompetent murine models and syngeneic cancer cells,
      an approach that is incompatible with large screening campaigns. Here, we outline
      strategies conceived to detect surrogate markers of ICD in vitro and to screen
      large chemical libraries for putative ICD inducers, based on a high-content, high
      throughput platform that we recently developed. Such a platform allows for the
      detection of multiple DAMPs, like cell surface-exposed calreticulin,
      extracellular ATP and high mobility group box 1 (HMGB1), and/or the processes
      that underlie their emission, such as endoplasmic reticulum stress, autophagy and
      necrotic plasma membrane permeabilization. We surmise that this technology will
      facilitate the development of next-generation anticancer regimens, which kill
      malignant cells and simultaneously convert them into a cancer-specific
      therapeutic vaccine.

PMID- 25941629
TI  - Novel insights into structure-function mechanism and tissue-specific expression
      profiling of full-length dxr gene from Cymbopogon winterianus.
AB  - The 1-deoxy-d-xylulose-5-phosphate reductoisomerase (DXR; EC1.1.1.267), an NADPH
      dependent reductase, plays a pivotal role in the methylerythritol 4-phosphate
      pathway (MEP), in the conversion of 1-deoxy-d-xylulose-5-phosphate (DXP) into
      MEP. The sheath and leaf of citronella (Cymbopogon winterianus) accumulates large
      amount of terpenes and sesquiterpenes with proven medicinal value and economic
      uses. Thus, sequencing of full length dxr gene and its characterization seems to
      be a valuable resource in metabolic engineering to alter the flux of isoprenoid
      active ingredients in plants. In this study, full length DXR from citronella was
      characterized through in silico and tissue-specific expression studies to explain
      its structure-function mechanism, mode of cofactor recognition and differential
      expression. The modelled DXR has a three-domain architecture and its active site
      comprised of a cofactor (NADPH) binding pocket and the substrate-binding pocket.
      Molecular dynamics simulation studies indicated that DXR model retained most of
      its secondary structure during 10 ns simulation in aqueous solution. The modelled
      DXR superimposes well with its closest structural homolog but subtle variations
      in the charge distribution over the cofactor recognition site were noticed.
      Molecular docking study revealed critical residues aiding tight anchoring NADPH
      within the active pocket of DXR. Tissue-specific differential expression analysis
      using semi-quantitative RT-PCR and qRT-PCR in various tissues of citronella plant
      revealed distinct differential expression of DXR. To our knowledge, this is the
      first ever report on DXR from the important medicinal plant citronella and
      further characterization of this gene will open up better avenues for metabolic
      engineering of secondary metabolite pathway genes from medicinal plants in the
      near future. 

PMID- 25941630
TI  - Antipsychotics inhibit glucose transport: Determination of olanzapine binding
      site in Staphylococcus epidermidis glucose/H(+) symporter.
AB  - The antipsychotic drug olanzapine is widely prescribed to treat schizophrenia and
      other psychotic disorders. However, it often causes unwanted side effects,
      including diabetes, due to disruption of insulin-dependant glucose metabolism
      through a mechanism yet to be elucidated. To determine if olanzapine can affect
      the first step in glucose metabolism - glucose transport inside cells - we
      investigated the effect of this drug on the transport activity of a model glucose
      transporter. The glucose transporter from Staphylococcus epidermidis (GlcPSe) is
      specific for glucose, inhibited by various human glucose transporter (GLUT)
      inhibitors, has high sequence and structure homology to GLUTs, and is readily
      amenable to transport assay, mutagenesis, and computational modeling. We found
      that olanzapine inhibits glucose transport of GlcPSe with an IC50 0.9 +/- 0.1 mM.
      Computational docking of olanzapine to the GlcPSe structure revealed potential
      binding sites that were further examined through mutagenesis and transport assay
      to identify residues important for olanzapine inhibition. These investigations
      suggest that olanzapine binds in a polar region of the cytosolic part of the
      transporter, and interacts with residues R129, strictly conserved in all GLUTs,
      and N136, conserved in only a few GLUTs, including the insulin-responsive GLUT4.
      We propose that olanzapine inhibits GlcPSe by impeding the alternating opening
      and closing of the substrate cavity necessary for glucose transport. It
      accomplishes this by disrupting a key salt bridge formed by conserved residues
      R129 and E362, that stabilizes the outward-facing conformation of the
      transporter. 

PMID- 25941631
TI  - Blocking c-Met signaling enhances bone morphogenetic protein-2-induced osteoblast
      differentiation.
AB  - We previously demonstrated that blocking hepatocyte growth factor (HGF)
      receptor/c-Met signaling inhibited arthritis and articular bone destruction in
      mouse models of rheumatoid arthritis (RA). In the present study, we investigated
      the role of c-Met signaling in osteoblast differentiation using the C2C12
      myoblast cell line derived from murine satellite cells and the MC3T3-E1 murine
      pre-osteoblast cell line. Osteoblast differentiation was induced by treatment
      with bone morphogenetic protein (BMP)-2 or osteoblast-inducer reagent in the
      presence or absence of either HGF antagonist (NK4) or c-Met inhibitor (SU11274).
      Osteoblast differentiation was confirmed by Runx2 expression, and alkaline
      phosphatase (ALP) and osteocalcin production by the cells. Production of ALP,
      osteocalcin and HGF was verified by enzyme-linked immunosorbent assay. Runx2
      expression was confirmed by reverse transcription-PCR analysis. The
      phosphorylation status of ERK1/2, AKT, and Smads was determined by Western blot
      analysis. Both NK4 and SU11274 enhanced Runx2 expression, and ALP and osteocalcin
      production but suppressed HGF production in BMP-2-stimulated C2C12 cells. SU11274
      also enhanced ALP and osteocalcin production in osteoblast-inducer reagent
      stimulated MC3T3-E1 cells. SU11274 inhibited ERK1/2 and AKT phosphorylation in
      HGF-stimulated C2C12 cells. This result suggested that ERK and AKT were
      functional downstream of the c-Met signaling pathway. However, both mitogen
      activated protein kinase/ERK kinase (MEK) and phosphatidylinositol 3-kinase
      (PI3K) inhibitor suppressed osteocalcin and HGF production in BMP-2-stimulated
      C2C12 cells. Furthermore, SU11274, MEK, and PI3K inhibitor suppressed Smad
      phosphorylation in BMP-2-stimulated C2C12 cells. These results indicate that
      although the c-Met-MEK-ERK-Smad and c-Met-PI3K-AKT-Smad signaling pathways
      positively regulate osteoblast differentiation, c-Met signaling negatively
      regulates osteoblast differentiation, independent of the MEK-ERK-Smad and PI3K
      AKT-Smad pathways. Therefore, blocking c-Met signaling might serve as a
      therapeutic strategy for the repair of destructed bone in patients with RA. 

PMID- 25941632
TI  - Pyrenochaeta romeroi causing subcutaneous phaeohyphomycotic cyst in a diabetic
      female.
AB  - Opportunistic subcutaneous fungal infections are increasing in present times due
      to increasing incidence of many medical conditions causing immunosupression like
      diabetes, AIDS, organ transplant recipients and anticancer therapy. Pyrenochaeta
      romeroi, a fungus from the dematiaceae group, first described by Borelli in 1959,
      is saprophyte to soil and plants.We present a rare case of subcutaneous
      phaeohyphomycotic cyst in a diabetic female caused by P. romeroi. 

PMID- 25941633
TI  - Structural and functional analyses of Barth syndrome-causing mutations and
      alternative splicing in the tafazzin acyltransferase domain.
AB  - Tafazzin is a mitochondrial phospholipid transacylase, and its mutations cause
      Barth syndrome (BTHS). Human tafazzin gene produces four distinct alternatively
      spliced transcripts. To understand the molecular mechanisms of tafazzin
      deficiency, we performed an atomic resolution analysis of the influence of the
      BTHS mutations and of alternative splicing on the structure and function of
      tafazzin. From the three-dimensional (3D) homology modeling of tafazzin, we
      identified candidate amino acid residues that contribute to cardiolipin binding
      and to mitochondrial membrane associations that facilitate acyl-transfer
      reactions. Primate specific exon 5, which is alternatively spliced, is predicted
      to correspond to an intrinsically unstructured region in the protein. We proposed
      that this region should change the substrate-binding affinity and/or contribute
      to primate-specific molecular interactions. Exon 7, another alternatively spliced
      exon, encodes a region forming a part of the putative substrate-binding cleft,
      suggesting that the gene products lacking exon 7 will lose their substrate
      binding ability. We demonstrate a clear localization of the BTHS mutations at
      residues responsible for membrane association, substrate binding, and the
      conformational stability of tafazzin. These findings provide new insights into
      the function of defective tafazzin and the pathogenesis of BTHS at the level of
      protein 3D structure and the evolution of alternatively spliced exons in
      primates. 

PMID- 25941634
TI  - Analysis of consequences of non-synonymous SNP in feed conversion ratio
      associated TGF-beta receptor type 3 gene in chicken.
AB  - The recent advances in high throughput sequencing technology accelerate possible
      ways for the study of genome wide variation in several organisms and associated
      consequences. In the present study, mutations in TGFBR3 showing significant
      association with FCR trait in chicken during exome sequencing were further
      analyzed. Out of four SNPs, one nsSNP p.Val451Leu was found in the coding region
      of TGFBR3. In silico tools such as SnpSift and PANTHER predicted it as
      deleterious (0.04) and to be tolerated, respectively, while I-Mutant revealed
      that protein stability decreased. The TGFBR3 I-TASSER model has a C-score of
      0.85, which was validated using PROCHECK. Based on MD simulation, mutant protein
      structure deviated from native with RMSD 0.08 A due to change in the H-bonding
      distances of mutant residue. The docking of TGFBR3 with interacting TGFBR2
      inferred that mutant required more global energy. Therefore, the present study
      will provide useful information about functional SNPs that have an impact on FCR
      traits. 

PMID- 25941635
TI  - Initial description of primate-specific cystine-knot Prometheus genes and
      differential gene expansions of D-dopachrome tautomerase genes.
AB  - Using eutherian comparative genomic analysis protocol and public genomic sequence
      data sets, the present work attempted to update and revise two gene data sets.
      The most comprehensive third party annotation gene data sets of eutherian
      adenohypophysis cystine-knot genes (128 complete coding sequences), and d
      dopachrome tautomerases and macrophage migration inhibitory factor genes (30
      complete coding sequences) were annotated. For example, the present study first
      described primate-specific cystine-knot Prometheus genes, as well as differential
      gene expansions of D-dopachrome tautomerase genes. Furthermore, new frameworks of
      future experiments of two eutherian gene data sets were proposed. 

PMID- 25941636
TI  - Diabetes-friendly environments for children with diabetes.

PMID- 25941637
TI  - Type 1 diabetes care updates: Tanzania.
AB  - Tanzania is located in east Africa with a population of 45 million. The country's
      population is growing at 2.5% annually. The International Diabetes Federation
      Child Sponsorship Program was launched in Tanzania in 2005. The number of type 1
      diabetes mellitus children enrolled in the changing diabetes in children program
      in Tanzania has augmented from almost below 50 in 2005 to over 1200 in 2014. The
      country had an overall trend of HbA1c value of 14% in 2005 while the same has
      reduced over the years to 10% in 2012-13. The program has been able to reduce the
      proportion of patients with HbA1c values of 11-14%; from 71.9% in 2008 to 49.8%
      in 2012-13. The challenges, which CDiC faces are misdiagnosis, low public
      awareness, and stigma especially in the reproductive age/adolescent groups. 

PMID- 25941638
TI  - Type 1 diabetes mellitus in Bhutan.
AB  - Bhutan is a South Asian country with a total population of 733,643. Bhutan has a
      very low burden of type 1 diabetes mellitus (T1DM), while that of type 2 diabetes
      mellitus is very high and increasing at alarming rates. Bhutan has a notably high
      proportion of over-weight and obese population. First case of T1DM was detected
      in 2006 and all the detected patients are in the age range of 14-15 years. The
      challenges in T1DM management include lack of knowledge among health care workers
      and patients, and limited access to health care services because of the difficult
      terrain. 

PMID- 25941639
TI  - Trials and tribulations of managing type 1 diabetes.
AB  - Effective type 1 diabetes mellitus (T1DM) management tools are education,
      empowerment, insulin, and diet control. Exercise should be of moderate intensity
      so as to avoid hypoglycaemia. It is prudent to ensure that the required insulin
      levels are achieved in all children in order to manage the disorder well. The
      total daily dose of insulin may be 0.6-1.0 u/kg body weight, and it may be 2/3,
      1/3 for split mixed insulin, and 50/50 for multiple subcutaneous injections. The
      dosages for the pump also vary from child to child. Basal bolus regimen is
      important and necessary in all T1DM children. It is not necessary to use all
      types of insulin analogs in all T1DM children, and the decision should depend on
      cost and delivery limiting factors. The advantages of using analogues are that
      some of these exhibit low hypoglycemic events (especially nocturnal events with
      basal insulin) and a few offer flexibility of administration to patients (most
      prandial analogs and some basal analogs). 

PMID- 25941640
TI  - Type 1 diabetes guidelines: Are they enough?
AB  - The discovery of insulin by Banting and Best in 1922 changed the landscape of
      type 1 diabetes mellitus (T1DM). Guidelines on T1DM should be evidence based and
      should emphasize comprehensive risk management. Guidelines would improve
      awareness amongst governments, state health care providers and the general public
      about the serious long-term implications of poorly managed diabetes and of the
      essential resources needed for optimal care. T1DM requires lifelong daily
      medication, regular control as well as access to facilities to manage acute and
      chronic complications. American Diabetes Association 2014 guidelines recommends
      annual nephropathy screening for albumin levels; random spot urine sample for
      albumin-to-creatinine ratio at start of puberty or age >=10 years, whichever is
      earlier, once the child has had diabetes for 5 years. Hypertension should be
      screened for in T1DM patients by measuring blood pressure at each routine visit.
      Dyslipidemia in T1DM patients is important and patients should be screened if
      there is a family history of hypercholesterolemia or a cardiovascular event
      before the age of 55 years exists or if family history is unknown. Retinopathy is
      another important complication of diabetes and patients should be subjected to an
      initial dilated and comprehensive eye examination. Basic diabetes training should
      be provided for school staff, and they should be assigned with responsibilities
      for the care of diabetic children. Self-management should be allowed at all
      school settings for students. 

PMID- 25941641
TI  - Treatment essentials and training for health care providers.
AB  - The lack of awareness among health care providers (HCPs) is one of the biggest
      challenges for the management of patients with type 1 diabetes mellitus (T1DM) in
      India. Major challenges faced by HCPs include lack of awareness about the disease
      among general physicians and inadequately trained staff to deal with children
      with T1DM. The changing diabetes in children (CDiC) program is helping in
      overcoming these barriers faced by HCPs. CDiC provides treatment, monitoring
      tools, and education to children affected with T1DM and has been instrumental is
      developing various education and awareness tools. 

PMID- 25941642
TI  - Myths about type 1 diabetes: Awareness and education.
AB  - Not all healthcare professionals (HCPs) are aware of type 1 diabetes mellitus
      (T1DM) and various myths still exist in the society and among HCPs. The medical
      challenge in treating T1DM is the confusion between T1DM and T2DM and its
      management, which is very common and is observed with both general practitioners
      and parents of children with diabetes. There are multiple medical and social
      myths associated with diabetes, especially T1DM, prevalent in society. Diabetes
      management requires support and collaboration from family, school and society,
      which is sometimes difficult, as they are more discouraging than positive. The
      launch of the Changing Diabetes in Children program in India has created a lot of
      awareness and is helping patients and their parents understand the disease. 

PMID- 25941643
TI  - Creativity and diabetes education: Essentiality, impact and way forward.
AB  - The changing diabetes in children (CDiC) program is a unique program aimed at
      children suffering from type 1 diabetes. The whole focus of CDiC is to provide
      comprehensive care including diabetes education. Various innovative and creative
      diabetes educational materials have been developed, which makes learning fun. Lot
      of diabetes camps are held at CDiC, focusing on diabetes education, experience
      sharing and fun activities. CDiC faces many challenges in an effort to cater to
      the needs of most deserving children with type 1 diabetes mellitus (T1DM)
      throughout the country, to provide comprehensive care including self-sufficiency,
      to serve children for as long as possible and to ultimately have better outcomes
      for all children with T1DM. The CDiC program aims to make the child more
      positive, secure and hopeful and initiate and strive for comprehensive diabetes
      care for the economically underprivileged children with T1DM. 

PMID- 25941644
TI  - Managing type 1 diabetes in remote and challenging locations in India.
AB  - Type 1 diabetes mellitus is a challenging situation for both physician and
      patient, as it requires a very disciplined lifestyle with regular monitoring and
      follow-up. It becomes even more difficult when facilities are limited. Manipur
      has a difficult terrain and due to lack of adequate facilities patients face
      frequent hypoglycemic episodes and hyperglycemic crises. Continuous availability
      of insulin is not possible at all times. The health care workers in the state are
      not fully aware of right practices and incorrect injection sites and erroneous
      techniques are also quite prevalent. Some quacks and traditional healers claim
      that they can cure diabetes by their indigenous preparation. 

PMID- 25941645
TI  - Type 1 diabetes in India: Overall insights.
AB  - Type 1 diabetes mellitus (T1DM) is also on increase like type 2 diabetes, even
      though not in the same proportion, but still with a trend of 3-5% increase/year.
      India has three new cases of T1DM/100,000 children of 0-14 years. Three sets of
      prevalence data shows 17.93 cases/100,000 children in Karnataka, 3.2
      cases/100,000 children in Chennai, and 10.2 cases/100,000 children in Karnal
      (Haryana). T1DM may be autoimmune or idiopathic in nature and is present in 9%
      cases of insulin deficiency. T1DM is primarily caused by genetic factors,
      environmental factors, and disorder of the immune regulatory mechanism. A
      combination of all these three factors causes autoimmune disease, which may
      ultimately result in the destruction of pancreatic beta cells leading to
      hyperglycemia, ketoacidosis and potentially death, if not treated with insulin.
      Prediabetes is the phase before the onset of T1DM, which provides a window of
      opportunity for early intervention. All available interventions including
      steroids, immunosuppressants, and cyclosporins can be possibly applied during the
      prediabetes phase. The treatment goals for T1DM are simple and include
      maintaining near normal blood glucose levels and avoiding long-term
      complications, which is a constant juggle between insulin and maintaining an
      appropriate lifestyle. The Indian Council of Medical Research funded Registry of
      People with diabetes in India with young age at onset (YDR) was started in the
      year 2006 with 10 collaborating centres across India. This registry is focusing
      on to provide an overview of diabetes in the young. 

PMID- 25941646
TI  - Incidence trends for childhood type 1 diabetes in India.
AB  - It is estimated that India is housing about 97,700 children with type 1 diabetes
      mellitus (T1DM). A study of 30 children with insulin-dependent diabetes with age
      at diagnosis <=15 years, conducted in 1992, reported a prevalence of 0.26/1000
      children. The peak age at diagnosis was 12 years. This was the first population
      based study of prevalence of insulin-dependent diabetes in South India and shows
      that insulin-dependent diabetes is not rare and is higher than that reported from
      many other Asian countries. The Karnataka state T1DM registry listed an incidence
      of 3.7/100,000 in boys and 4.0/100,000 in girls over 13 years of data collection.
      At Karnal, in Haryana, the prevalence of T1DM is 26.6/100,000 in urban and
      4.27/100,000 in rural areas of the district, leading to an average prevalence of
      10.20/100,000 population. Karnal city has a relatively high prevalence of T1DM
      (31.9/100,000). An estimated 18,000 children under the age of 15 were newly
      diagnosed for T1DM in the year 2011 in the above-mentioned regions. The
      prevalence of T1DM in children is 111,500 according to a World Health
      Organization report of the International Diabetes Federation for the South-East
      Asian Region. 

PMID- 25941647
TI  - Preventing microvascular complications in type 1 diabetes mellitus.
AB  - Patients with complications of diabetes such as retinopathy, nephropathy, and
      cardiovascular complications have increased hospital stay with greater economic
      burden. Prevention of complications should be started before the onset of type 1
      diabetes mellitus (T1DM) by working on risk factors and thereafter by
      intervention upon confirmatory diagnosis which can prevent further damage to beta
      cells. The actual risk of getting microvascular complications like
      microalbuminuria and retinopathy progression starts at glycated hemoglobin
      (HbA1c) level of 7%. As per the American Diabetes Association, a new pediatric
      glycemic control target of HbA1c <7.5% across all ages replaces previous
      guidelines that had called for different targets by age. Evidence shows that
      prevalence of microvascular complications is greater in patients with age >20
      years as compared to patients <10 years of age. Screening of these complications
      should be done regularly, and appropriate preventive strategies should be
      followed. Angiotensin converting enzyme inhibitors and angiotensin II receptor
      blocker reduce progression from microalbuminuria to macroalbuminuria and increase
      the regression rate to normoalbuminuria. Diabetic microvascular complications can
      be controlled with tight glycemic therapy, dyslipidemia management and blood
      pressure control along with renal function monitoring, lifestyle changes,
      including smoking cessation and low-protein diet. An integrated and personalized
      care would reduce the risk of development of microvascular complications in T1DM
      patients. The child with diabetes who receives limited care is more likely to
      develop long-term complications at an earlier age. Screening for subclinical
      complications and early interventions with intensive therapy is the need of the
      hour. 

PMID- 25941648
TI  - Understanding type 1 diabetes through genetics: Advances and prospects.
AB  - The largest contribution of type 1 diabetes mellitus (T1DM) from a single locus
      comes from several genes located in the major histocompatibility complex on
      chromosome 6p21. Because DQB1 is the best single genetic marker for T1DM, it is
      the gene most often used to identify individuals with a high risk of developing
      disease. As per the data collected from the All India Institute of Medical
      Sciences, among the human leukocyte antigen (HLA)-DRB1 genes, HLA-DR3 showed
      strongest association with the disease; however, unlike Caucasians and other
      populations, DR4 was not significantly increased in these patients. HLA-DR10, 11,
      13, and 15 showed a negative association with the disease as they were reduced in
      these patients. In India, the relative risk of developing T1DM is higher with the
      DR3-DQ2 haplotypes as compared to DR4-DQ8 haplotypes. Studies have shown that in
      North India, the relative risk for T1DM is comparatively higher (>30) with the
      DQ2/DQ8 genotype, but is relatively lower (approximately 18) for the DQ2/DQ2
      genotype. In addition, the three sets of HLA-B-DR3 haplotypes, mainly B58-DR3,
      B50-DR3, and B8-DR3 have shown to have modulated susceptibility for T1DM in India
      and worldwide. New interventions that will be tested in the future will be
      conducted through T1DM TrialNet, a collaborative network of clinical centers and
      experts in diabetes and immunology. These studies will identify unaffected first
      degree relatives with beta cell autoantibodies who will be eligible for new
      interventions. 

PMID- 25941649
TI  - Diabetes therapy by the ear: A bi-directional process.

PMID- 25941650
TI  - Key elements of successful intensive therapy in patients with type 1 diabetes.
AB  - An intensified diabetes management approach (including increased education,
      monitoring, and contact with diabetes team) should be used for adolescents and
      also for younger children if glycaemic control is not achieved by insulin
      therapy. Treatment options may include increased frequency of injections (e.g.
      the patients on 2 bolus may require 3 or 4 bolus injections), change in the type
      of basal and/or bolus insulin depending on multiple times monitoring for
      adolescents and for younger children, and change to continuous subcutaneous
      insulin infusion pump therapy. Results of epidemiology of diabetes interventions
      and complications (EDIC) Research Group, where the Diabetes Control and
      Complications Trial patients were further followed up almost for a period of 7
      years or more showed that intensive therapy significantly reduced and maintained
      glycated hemoglobin with relative risk reduction of microvascular complications
      in the intensive therapy group. In addition, intensive treatment reduced the risk
      of any cardiovascular disease (CVD) event by 42% and the risk of nonfatal
      myocardial infarction, stroke, or death from CVD by 57%. The reduction of
      microvascular and macrovascular events in the intensively-treated group persisted
      due to the "legacy effect" or "metabolic memory" of early intensive glycemic
      control. The main advantage of intensive insulin therapy is that it reduces the
      rate of diabetes complications, in the long run. Furthermore, it offers
      flexibility as the doses can be adjusted according to the activity and food
      consumed. The main disadvantage of intensive insulin therapy is the risk of
      hypoglycemia especially in type 1 diabetes mellitus and weight gain. 

PMID- 25941651
TI  - Type 2 diabetes in children: Clinical aspects and risk factors.
AB  - A strong link between obesity, insulin resistance, and metabolic syndrome has
      been reported with development of a new paradigm to type 2 diabetes mellitus
      (T2DM), with some evidence suggesting that beta-cell dysfunction is present
      before the onset of impaired glucose tolerance. Differentiating type 1 diabetes
      mellitus (T1DM) from T2DM is actually not very easy and there exists a number of
      overlapping characteristics. The autoantibody frequencies of seven antigens in
      T1DM patients may turn out to be actually having T2DM patients (pre-T2DM). T2DM
      patients generally have increased C-peptide levels (may be normal at time of
      diagnosis), usually no auto-antibodies, strong family history of diabetes, obese
      and show signs of insulin resistance (hypertension, acanthosis, PCOS). The
      American Academy of Paediatrics recommends lifestyle modifications +/- metformin
      when blood glucose is 126-200 mg/dL and hemoglobin A1c (HbA1c) <8.5. Insulin is
      recommended when blood glucose is >200 mg/dL and HbA1c >8.5, with or without
      ketosis. Metformin is not recommended if the patient is ketotic, because this
      increases the risk of lactic acidosis. Metformin is currently the only oral
      hypoglycemic that has been approved for use in children. Knowing these subtle
      differences in mechanism, and knowing how to test patients for which mechanism
      (s) are causing their diabetes mellitus, may help us eventually tailor treatment
      programs on an individual basis. 

PMID- 25941652
TI  - Puberty and type 1 diabetes.
AB  - Various data on type 1 diabetes mellitus (T1DM) have showed that the incidence of
      T1DM peaks at puberty. However, diabetes control and complications could be
      adversely affected by the physiological changes of puberty. In early years of
      insulin therapy, severe growth retardation with pubertal delay, like in Mauriac
      syndrome, have been reported. Insulin and leptin are metabolic factors,
      circulating in the periphery, which participate in the hypothalamic control of
      metabolism and reproduction. Insulin may be an important regulator of leptin in
      humans. Increased levels of advanced glycation end products suppress activation
      of the gonadotropin-releasing hormone (GnRH) pulse generator, resulting in
      pubertal delay. Glycemic control deteriorates during puberty as the lean body
      mass doubles mainly over a period of 25 years, which increases insulin
      requirement. There is also an increase in insulin resistance over the period of
      puberty. In normal individuals, fasting and postprandial insulin concentrations
      reach a peak in both sexes in mid to late puberty. Puberty, at all stages, has
      the worst insulin resistance. It has been observed that an excessive GH secretion
      in T1DM during puberty has significant effects on ketogenesis. Adolescent T1DM
      tends to decompensate very rapidly and develop ketoacidosis when the late night
      insulin dose is omitted. Adolescence is a critical developmental phase that
      presents unique challenges and opportunities to individuals with diabetes, their
      families and their healthcare providers. 

PMID- 25941653
TI  - Diabetic ketoacidosis in children and adolescents.
AB  - Diabetic ketoacidosis (DKA) is considered to be a common presentation of both
      type 1 diabetes mellitus and type 2 diabetes mellitus in children and
      adolescents. DKA arises due to lack of adequate insulin in the body. Insulin
      stops the use of fat as an energy source by inhibiting the peptide hormone
      glucagon. Without insulin, glucagon levels rise resulting in the release of free
      fatty acids from adipose tissue, as well as amino acids from muscle cells.
      Neurological observations should be made for warning signs and symptoms of
      cerebral edema, and capillary blood glucose concentration should be measured on
      an hourly basis. Every 2-4 h electrolytes, blood gases, and beta-hydroxybutyrate
      should be measured. Cerebral edema occurs in 0.5-0.9% of all episodes of DKA. It
      is considered to be a major cause of death in childhood DKA. Treatment of
      cerebral edema should be prompt and immediate. Successful DKA management in
      children depends upon swift diagnosis, meticulous monitoring of clinical and
      biochemical parameters with prompt intervention. 

PMID- 25941654
TI  - Type 1 diabetes pathogenesis - Prevention???
AB  - Pathogenesis of type 1 diabetes is multi-faceted, including, autoimmunity,
      genetics and environment. Autoimmunity directed against pancreatic islet cells
      results in slowly progressive selective beta-cell destruction ("Primary
      autoimmune insulitis"), culminating over years in clinically manifested insulin
      dependent diabetes mellitus (IDDM). Circulating serum autoantibodies directed
      against the endocrine cells of the islets of Langerhans (Islet cell
      autoantibodies - ICAb) are an important hallmark of this disease. Assays for
      islet cell autoantibodies have facilitated the investigation and understanding of
      several facets in the pathogenesis of autoimmune diabetes. Their applications
      have extended into clinical practice and have opened new avenues for early
      preclinical prediction and preventive prophylaxis in IDDM/type 1 DM. Recently,
      surprisingly, differences in insulin content between T1DM islets, as well as,
      'patchy' or 'lobular' destruction of islets have been described. These unique
      pathobiological phenomena, suggest that beta cell destruction may not always be
      inexorable and inevitably complete/total, and thus raise hopes for possible
      therapeutic interruption of beta cell autoimmunity - destruction and cure of type
      1 diabetes. "Recurrent or secondary autoimmune insulitis" refers to the rapid
      reappearance of islet cell autoantibodies post pancreas transplant, and selective
      islet beta cell destruction in the grafted pancreas [never forgetting or
      "anamnestic" beta cell destructive memory], in the absence of any graft pancreas
      rejection [monozygotic twin to twin transplantation]. The one definite
      environmental factor is congenital rubella, because of which a subset of children
      subsequently develop type 1 diabetes. The putative predisposing factors are
      viruses, gluten and cow's milk. The putative protective factors include gut
      flora, helminths, viral infections, and Vitamin D. Prevention of T1DM can
      include: Primary prevention strategies before the development of autoantibodies
      and Secondary prevention regimens after autoantibody development. Once islet cell
      autoantibodies have developed, the goal is to establish a therapeutic regimen to
      preserve at least 90% of the beta cells, and prevent the development of
      hyperglycaemia. The targets for T1DM reversal should include autoimmunity, beta
      cell regeneration and protection of beta cell mass. Anti-CD3 teplizumab and anti
      CD3 otelixizumab have been shown to provide C-peptide preservation. The
      unanswered questions in diabetes research include elimination of autoimmune
      memory responses, reestablishment of immune self-tolerance, and mechanisms of
      disease initiation. 

PMID- 25941656
TI  - Growth disorders in type 1 diabetes: an Indian experience.
AB  - Though children with type 1 diabetes mellitus (T1DM) are often tall at the time
      of diagnosis, they may experience growth retardation, pubertal delay or both,
      which may be due to poor glycemic control, associated diseases or chronic
      complications. Factors affecting growth include: gender, genetic environment, age
      at diagnosis, diabetes duration, puberty, metabolic control, and status of growth
      hormone (GH), insulin-like growth factors (IGFs), and IGF binding proteins
      (IGFBPs). Insulin regulates expression of hepatic GH receptors, affects IGFs and
      IGFBPs synthesis by modulating GH postreceptor events, and significantly
      increases IGF-I bioactivity. Low portal insulin seen in T1DM leads to GH
      hypersecretion, low circulating IGF-I and IGFBP-3, and high circulating IGFBP-1.
      Newly diagnosed T1DM patients have decreased GHBP which can be restored with
      insulin therapy. Growth velocity should be appropriate for the age of the
      child/adolescent, and the mid-parental height. Height, weight and blood pressure
      (BP) should be measured and plotted on a growth chart at least 2-3 times a year.
      Puberty should also be assessed annually. Following precautions are to be taken
      in T1DM children: checking for pubertal onset and ensuring it is not delayed,
      testing early when growth falters (hypothyroidism/celiac disease/puberty/other
      conditions), aiming for best possible metabolic control (multidose regimens,
      regardless of type of insulin), and encouraging dietary calcium and protein,
      exposure to sunlight, Vitamin D supplements and exercise. 

PMID- 25941655
TI  - Type 1 diabetes: Awareness, management and challenges: Current scenario in India.
AB  - Type 1 diabetes mellitus (T1DM) has a wide presence in children and has a high
      mortality rates. The disease, if left unmanaged, poses various challenges to the
      patient and healthcare providers, including development of diabetic complications
      and thus decreasing the life expectancy of the affected child. The challenges of
      T1DM include awareness of the disease that is very poor among the general public
      and also in parents of T1DM children along with the health care professionals.
      The challenge of lack of awareness of T1DM can be met by increasing public
      awareness programs, conducting workshops for diabetes educators regarding T1DM in
      children, newsletters, CMEs, online courses, and by structured teaching modules
      for diabetes educators. Diagnosis of T1DM was a challenge a few decades ago but
      the situation has improved today with diagnostic tests and facilities, made
      available even in villages. Investigation facilities and infrastructure, however,
      are very poor at the primary care level, especially in rural areas. Insulin
      availability, acceptability, and affordability are also major problems,
      compounded by the various types of insulin that are available in the market with
      a varied price range. But effective use of insulin remains a matter of utmost
      importance. 

PMID- 25941657
TI  - Initiating insulin therapy in children and adolescents with type 1 diabetes
      mellitus.
AB  - The primary clinical goals to be achieved with insulin initiation are elimination
      of ketosis and hyperglycemia with prevention of chronic complications. Insulin
      therapy is the mainstay in management of type 1 diabetes, which should be aimed
      at achieving good glycemic control, with achievement of hemoglobin A1c (HbA1c)
      <7.5%, pre-meal self-monitored blood glucose (SMBG) of 90-130 mg/dL, bed time
      SMBG of 100-140 mg/dL, mean blood glucose level of 120-160 mg/dL and no
      ketonuria. Two classes of insulin are available for use in T1DM viz.
      bolus/prandial insulins (rapid-acting insulins and short-acting insulins) and
      basal insulins (intermediate-acting insulin and long-acting insulin). Insulin
      glargine and glulisine can be used in children above 6 years, lispro in children
      above 3 years and detemir and aspart in children above 2 years. The caution for
      hypoglycemia should be exercised while prescribing them. Degludec is currently
      not approved for pediatric use. The initial insulin regimen should comprise of
      >=2 daily bolus and >=1 basal insulin injections. Insulin intensification would
      be required if the initial regimen fails, which can be achieved by increasing
      frequency of long and rapid acting insulin analogues. The American Diabetes
      Association guidelines recommend HbA1c targets of <8.0% for children <6 years of
      age, <=7.5% for children 6 to 12 years of age, and <=7.0% for adolescents, 12-18
      years of age. However, the evidence is now in favor of a single target HbA1c of
      <=7.5% for all children and adolescents <19 years of age. 

PMID- 25941658
TI  - Basal insulin analogues in the treatment of diabetes mellitus: What progress have
      we made?
AB  - Over the past few decades, continuous progress has been made in the development
      of insulin therapy. Basal insulins were developed around 60 years ago. However,
      existing basal insulins were found to have limitations. An ideal basal insulin
      should have the following properties viz. longer duration of action, a flat time
      action profile, low day-to-day glycaemic variability, and the potential for
      flexible dosing. Basal insulins have advanced over the years, from lectin and
      neutral protamine Hagedorn to the currently available insulin degludec.
      Currently, the focus is on developing a basal insulin that can give coverage for
      the entire day, with lesser variability and flexible administration. Insulin
      degludec has been a significant leap in that direction. In addition, U300 insulin
      glargine and pegylated lispro represent further developments in basal insulin
      pharmacotherapeutics. 

PMID- 25941659
TI  - Unique case from real life practice.
AB  - Type 1 diabetes mellitus (T1DM) is a form of diabetes mellitus that results from
      the autoimmune destruction of the insulin-producing beta cells in the pancreas.
      For economically backward children, understanding and dealing with the disorder
      can be quite challenging. Here, I describe a female with T1DM and how her
      enrolment into the changing diabetes in children program brought about a positive
      change for her. Financial, medical and psychological support at the right time
      will help these children to gain independence. 

PMID- 25941660
TI  - Type 1 diabetes mellitus-common cases.
AB  - Tight glycemic control in type 1 diabetes mellitus patients is associated with
      the risk of hypoglycemia. Diabetic patients are forced to change their lifestyle
      to adjust to the disease condition and survive it. The best way to manage
      diabetes would be to develop a therapy, which could adjust to the patient's
      conditions. Here, I present few cases wherein switching to a long-acting basal
      insulin analog helped combat recurrent hypoglycemic episodes experienced by the
      patients. 

PMID- 25941661
TI  - Real life with type 1 diabetes mellitus.
AB  - Type 1 diabetes mellitus (T1DM) is a form of diabetes mellitus that results from
      the autoimmune destruction of the insulin-producing beta cells in the pancreas.
      Those affected by this disorder have a challenging life, both in terms of health
      and social adjustments. Various "alternative medicines" are offered to them in an
      effort to cure. Research has shown that good control over diabetes can be
      maintained through regular self-monitoring of blood glucose and frequent checking
      of diabetic complications. Here, I describe a female with T1DM and her journey
      with the disorder. 

PMID- 25941662
TI  - Type 1 diabetes: The Bangladesh perspective.
AB  - Diabetes mellitus (DM) is a common endocrine disorder among children and
      adolescents in Bangladesh. The latest International Diabetes Federation atlas
      estimated the incidence of type 1 DM (T1DM) in Bangladesh as 4.2 new cases of
      T1DM/100,000 children (0-14 years)/year, in 2013. Diabetes, being a lifelong
      disease, places a huge burden on the economy of the most densely populated, and
      resource-poor country of the world. The Diabetic Association of Bangladesh
      (BADAS), the largest of its kind in the world, provides comprehensive care to the
      biggest number of diabetics at any one centre and is engaged in advocacy.
      Although sounding grandiose, it's aims that 'no diabetic shall die untreated,
      unfed or unemployed, even if poor' is pursued with a passion. Recently BADAS has
      been supported in its endeavor for children and adolescents by two programmes;
      viz the Changing Diabetes in Children program (a joint initiative of BADAS, the
      World Diabetes Foundation and Novo Nordisk), and the Life for a Child Programme
      (LFAC) supported by the IDF. Numerous studies from the prosperous countries have
      demonstrated the incidence of T1DM is increasing. Data from the CDiC clinic at
      BIRDEM shows a rising trend in patients presenting with classical T1DM. In
      addition, the pattern of DM is changing. 

PMID- 25941663
TI  - Peptide Hydrogels - Versatile Matrices for 3D Cell Culture in Cancer Medicine.
AB  - Traditional two-dimensional (2D) cell culture systems have contributed
      tremendously to our understanding of cancer biology but have significant
      limitations in mimicking in vivo conditions such as the tumor microenvironment.
      In vitro, three-dimensional (3D) cell culture models represent a more accurate,
      intermediate platform between simplified 2D culture models and complex and
      expensive in vivo models. 3D in vitro models can overcome 2D in vitro limitations
      caused by the oversupply of nutrients, and unphysiological cell-cell and cell
      material interactions, and allow for dynamic interactions between cells, stroma,
      and extracellular matrix. In addition, 3D cultures allow for the development of
      concentration gradients, including oxygen, metabolites, and growth factors, with
      chemical gradients playing an integral role in many cellular functions ranging
      from development to signaling in normal epithelia and cancer environments in
      vivo. Currently, the most common matrices used for 3D culture are biologically
      derived materials such as matrigel and collagen. However, in recent years, more
      defined, synthetic materials have become available as scaffolds for 3D culture
      with the advantage of forming well-defined, designed, tunable materials to
      control matrix charge, stiffness, porosity, nanostructure, degradability, and
      adhesion properties, in addition to other material and biological properties. One
      important area of synthetic materials currently available for 3D cell culture is
      short sequence, self-assembling peptide hydrogels. In addition to the review of
      recent work toward the control of material, structure, and mechanical properties,
      we will also discuss the biochemical functionalization of peptide hydrogels and
      how this functionalization, coupled with desired hydrogel material
      characteristics, affects tumor cell behavior in 3D culture. 

PMID- 25941666
TI  - Ventilation before Umbilical Cord Clamping Improves Physiological Transition at
      Birth or "Umbilical Cord Clamping before Ventilation is Established Destabilizes
      Physiological Transition at Birth".

PMID- 25941665
TI  - Antimicrobial activities of chicken beta-defensin (4 and 10) peptides against
      pathogenic bacteria and fungi.
AB  - Host Defense Peptides (HDPs) are small cationic peptides found in several
      organisms. They play a vital role in innate immunity response and
      immunomodulatory stimulation. This investigation was designed to study the
      antimicrobial activities of beta-defensin peptide-4 (sAvBD-4) and 10 (sAvBD-4)
      derived from chickens against pathogenic organisms including bacteria and fungi.
      Ten bacterial strains and three fungal species were used in investigation. The
      results showed that the sAvBD-10 displayed a higher bactericidal potency against
      all the tested bacterial strains than that of sAvBD-4. The exhibited bactericidal
      activity was significant against almost the different bacterial strains at
      different peptide concentrations except for that of Pseudomonas aeruginosa (P.
      aeruginosa) and Streptococcus bovis (Str. bovis) strains where a moderate effect
      was noted. Both peptides were effective in the inactivation of fungal species
      tested yielding a killing rate of up to 95%. The results revealed that the
      synthetic peptides were resistant to salt at a concentration of 50 mM NaCl.
      However, they lost antimicrobial potency when applied in the presence of high
      salt concentrations. Based on blood hemolysis studies, a little hemolytic effect
      was showed in the case of both peptides even when applied at high concentrations.
      The data obtained from this study indicated that synthetic avian peptides exhibit
      strong antibacterial and antifungal activity. In conclusion, future work and
      research should be tailored to a better understanding of the mechanisms of action
      of those peptides and their potential use in the pharmaceutical industry to help
      reduce the incidence and impact of infectious agent and be marketed as a
      naturally occurring antibiotic. 

PMID- 25941667
TI  - Prevalence of Non-Nutritive Sucking Habits and Potential Influencing Factors
      among Children in Urban Communities in Nigeria.
AB  - BACKGROUND: The use of non-nutritive sucking materials like pacifiers and fingers
      poses health challenges to children in resource-limited settings, where hygiene
      practices and provision of clean water are poor. This study was designed to
      determine the prevalence of non-nutritive sucking habits and its association with
      acute diarrhea in children aged 6-23 months in urban communities of Nigeria.
      METHODS: In this cross-sectional study, 12 communities from 4 out of 12
      geopolitical wards in Ibadan North Local Government Area and 427 mothers of
      children aged 6-24 months were randomly selected. A pre-tested, interviewer
      administered questionnaire was used to obtain information on socio-demographic
      characteristics, recent history of diarrhea (3 months prior to visit) and use of
      non-nutritive sucking materials. Descriptive statistics, Chi-square, and logistic
      regression were used for data analysis at p = 0.05. RESULTS: Mean age of the
      children was 13.9 +/- 5.3 months and 50.6% were males. Prevalence of non
      nutritive sucking was 45.2%. Prevalence of non-nutritive sucking was not
      significantly different between males (45.8%) and females (44.5%). The odds ratio
      of engaging in non-nutritive sucking increases by 6.0% with increasing age (OR =
      1.06; 1.02; 1.10). More children who were not exclusively breastfed (53.5%) than
      exclusively breastfed (26.2%) were likely to engage in non-nutritive sucking (OR
      = 3.25; 95% CI = 2.07, 5.12). Acute diarrhea was more frequently reported in non
      nutritive sucking group than the other (OR = 1.51; 95% CI = 1.03, 2.22).
      CONCLUSION: Non-nutritive sucking was linked with failure to practice exclusive
      breastfeeding, worse with increasing age, and predisposes to acute diarrhea.
      Further studies are necessary to verify the nature of these associations.

PMID- 25941668
TI  - Threshold-free measures for assessing the performance of medical screening tests.
AB  - BACKGROUND: The area under the receiver operating characteristic curve (AUC) is
      frequently used as a performance measure for medical tests. It is a threshold
      free measure that is independent of the disease prevalence rate. We evaluate the
      utility of the AUC against an alternate measure called the average positive
      predictive value (AP), in the setting of many medical screening programs where
      the disease has a low prevalence rate. METHODS: We define the two measures using
      a common notation system and show that both measures can be expressed as a
      weighted average of the density function of the diseased subjects. The weights
      for the AP include prevalence in some form, but those for the AUC do not. These
      measures are compared using two screening test examples under rare and common
      disease prevalence rates. RESULTS: The AP measures the predictive power of a
      test, which varies when the prevalence rate changes, unlike the AUC, which is
      prevalence independent. The relationship between the AP and the prevalence rate
      depends on the underlying screening/diagnostic test. Therefore, the AP provides
      relevant information to clinical researchers and regulators about how a test is
      likely to perform in a screening population. CONCLUSION: The AP is an attractive
      alternative to the AUC for the evaluation and comparison of medical screening
      tests. It could improve the effectiveness of screening programs during the
      planning stage.

PMID- 25941664
TI  - Stress responses from the endoplasmic reticulum in cancer.
AB  - The endoplasmic reticulum (ER) is a dynamic organelle that is essential for
      multiple cellular functions. During cellular stress conditions, including
      nutrient deprivation and dysregulation of protein synthesis, unfolded/misfolded
      proteins accumulate in the ER lumen, resulting in activation of the unfolded
      protein response (UPR). The UPR also contributes to the regulation of various
      intracellular signaling pathways such as calcium signaling and lipid signaling.
      More recently, the mitochondria-associated ER membrane (MAM), which is a site of
      close contact between the ER and mitochondria, has been shown to function as a
      platform for various intracellular stress responses including apoptotic
      signaling, inflammatory signaling, the autophagic response, and the UPR.
      Interestingly, in cancer, these signaling pathways from the ER are often
      dysregulated, contributing to cancer cell metabolism. Thus, the signaling pathway
      from the ER may be a novel therapeutic target for various cancers. In this
      review, we discuss recent research on the roles of stress responses from the ER,
      including the MAM. 

PMID- 25941669
TI  - Health spending follows pace of population aging: challenges lying ahead of the
      largest Western balkan market.

PMID- 25941670
TI  - Success of the undergraduate public health at tulane university.
AB  - Tulane University School of Public Health and Tropical Medicine launched the
      Bachelors of Science in Public Health (BSPH) in 2005. The BSPH has steadily grown
      and comprises one-third of the total enrollment in the school. A review of the
      organizational structure demonstrates that direct responsibility for
      undergraduate education by a school of public health is advantageous to the
      success of the program. The competency and skills-based curriculum attracts
      students. Outcome measures show the enrollment is steadily increasing. The
      majority of the BSPH graduates continue onto competitive graduate and
      professional degree programs. Those who seek jobs find employment related to
      their public health education, but outside of the traditional governmental public
      health agencies. The combined BSPH/masters of public health (MPH) degree is a
      pipeline for students to pursue a MPH and increases the likelihood students will
      pursue careers in public health. The range and depth of study in the bachelors
      program is continually examined. Topics once within the purview of graduate
      education are now being incorporated into undergraduate courses. Undergraduate
      public health is one of a number of factors that is influencing changes in the
      MPH degree. 

PMID- 25941671
TI  - Deciphering the photochemical mechanisms describing the UV-induced processes
      occurring in solvated guanine monophosphate.
AB  - The photophysics and photochemistry of water-solvated guanine monophosphate (GMP)
      are here characterized by means of a multireference quantum-chemical/molecular
      mechanics theoretical approach (CASPT2//CASSCF/AMBER) in order to elucidate the
      main photo-processes occurring upon UV-light irradiation. The effect of the
      solvent and of the phosphate group on the energetics and structural features of
      this system are evaluated for the first time employing high-level ab initio
      methods and thoroughly compared to those in vacuo previously reported in the
      literature and to the experimental evidence to assess to which extent they
      influence the photoinduced mechanisms. Solvated electronic excitation energies of
      solvated GMP at the Franck-Condon (FC) region show a red shift for the pipi(*) La
      and Lb states, whereas the energy of the oxygen lone-pair npi(*) state is blue
      shifted. The main photoinduced decay route is promoted through a ring-puckering
      motion along the bright lowest-lying La state toward a conical intersection (CI)
      with the ground state, involving a very shallow stationary point along the
      minimum energy pathway in contrast to the barrierless profile found in gas-phase,
      the point being placed at the end of the minimum energy path (MEP) thus endorsing
      its ultrafast deactivation in accordance with time-resolved transient and
      photoelectron spectroscopy experiments. The role of the npi(*) state in the
      solvated system is severely diminished as the crossings with the initially
      populated La state and also with the Lb state are placed too high energetically
      to partake prominently in the deactivation photo-process. The proposed mechanism
      present in solvated and in vacuo DNA/RNA chromophores validates the intrinsic
      photostability mechanism through CI-mediated non-radiative processes accompanying
      the bright excited-state population toward the ground state and subsequent
      relaxation back to the FC region. 

PMID- 25941672
TI  - A computational analysis of stoichiometric constraints and trade-offs in
      cyanobacterial biofuel production.
AB  - Cyanobacteria are a promising biological chassis for the synthesis of renewable
      fuels and chemical bulk commodities. Significant efforts have been devoted to
      improve the yields of cyanobacterial products. However, while the introduction
      and heterologous expression of product-forming pathways is often feasible, the
      interactions and incompatibilities of product synthesis with the host metabolism
      are still insufficiently understood. In this work, we investigate the
      stoichiometric properties and trade-offs that underlie cyanobacterial product
      formation using a computational reconstruction of cyanobacterial metabolism.
      First, we evaluate the synthesis requirements of a selection of cyanobacterial
      products of potential biotechnological interest. Second, the large-scale
      metabolic reconstruction allows us to perform in silico experiments that mimic
      and predict the metabolic changes that must occur in the transition from a growth
      only phenotype to a production-only phenotype. Applied to the synthesis of
      ethanol, ethylene, and propane, these in silico transition experiments point to
      bottlenecks and potential modification targets in cyanobacterial metabolism. Our
      analysis reveals incompatibilities between biotechnological product synthesis and
      native host metabolism, such as shifts in ATP/NADPH demand and the requirement to
      reintegrate metabolic by-products. Similar strategies can be employed for a large
      class of cyanobacterial products to identify potential stoichiometric
      bottlenecks. 

PMID- 25941673
TI  - Molecular structure of photosynthetic microbial biofuels for improved engine
      combustion and emissions characteristics.
AB  - The metabolic engineering of photosynthetic microbes for production of novel
      hydrocarbons presents an opportunity for development of advanced designer
      biofuels. These can be significantly more sustainable, throughout the production
      to-consumption lifecycle, than the fossil fuels and crop-based biofuels they
      might replace. Current biofuels, such as bioethanol and fatty acid methyl esters,
      have been developed primarily as drop-in replacements for existing fossil fuels,
      based on their physical properties and autoignition characteristics under
      specific combustion regimes. However, advances in the genetic engineering of
      microalgae and cyanobacteria, and the application of synthetic biology approaches
      offer the potential of designer strains capable of producing hydrocarbons and
      oxygenates with specific molecular structures. Furthermore, these fuel molecules
      can be designed for higher efficiency of energy release and lower exhaust
      emissions during combustion. This paper presents a review of potential fuel
      molecules from photosynthetic microbes and the performance of these possible
      fuels in modern internal combustion engines, highlighting which modifications to
      the molecular structure of such fuels may enhance their suitability for specific
      combustion regimes. 

PMID- 25941674
TI  - Evaluating lignocellulosic biomass, its derivatives, and downstream products with
      Raman spectroscopy.
AB  - The creation of fuels, chemicals, and materials from plants can aid in replacing
      products fabricated from non-renewable energy sources. Before using biomass in
      downstream applications, it must be characterized to assess chemical traits, such
      as cellulose, lignin, or lignin monomer content, or the sugars released following
      an acid or enzymatic hydrolysis. The measurement of these traits allows
      researchers to gage the recalcitrance of the plants and develop efficient
      deconstruction strategies to maximize yields. Standard methods for assessing
      biomass phenotypes often have experimental protocols that limit their use for
      screening sizeable numbers of plant species. Raman spectroscopy, a non
      destructive, non-invasive vibrational spectroscopy technique, is capable of
      providing qualitative, structural information and quantitative measurements.
      Applications of Raman spectroscopy have aided in alleviating the constraints of
      standard methods by coupling spectral data with multivariate analysis to
      construct models capable of predicting analytes. Hydrolysis and fermentation
      products, such as glucose and ethanol, can be quantified off-, at-, or on-line.
      Raman imaging has enabled researchers to develop a visual understanding of
      reactions, such as different pretreatment strategies, in real-time, while also
      providing integral chemical information. This review provides an overview of what
      Raman spectroscopy is, and how it has been applied to the analysis of whole
      lignocellulosic biomass, its derivatives, and downstream process monitoring. 

PMID- 25941676
TI  - The need for competency-based training in dental urgent care.

PMID- 25941675
TI  - Treatment and controversies in paraesophageal hernia repair.
AB  - BACKGROUND: Historically all paraesophageal hernias were repaired surgically,
      today intervention is reserved for symptomatic paraesophageal hernias. In this
      review, we describe the indications for repair and explore the controversies in
      paraesophageal hernia repair, which include a comparison of open to laparoscopic
      paraesophageal hernia repair, the necessity of complete sac excision, the routine
      performance of fundoplication, and the use of mesh for hernia repair. METHODS: We
      searched Pubmed for papers published between 1980 and 2015 using the following
      keywords: hiatal hernias, paraesophageal hernias, regurgitation, dysphagia,
      gastroesophageal reflux disease, aspiration, GERD, endoscopy, manometry, pH
      monitoring, proton pump inhibitors, anemia, iron-deficiency anemia, Nissen
      fundoplication, sac excision, mesh, and mesh repair. RESULTS: Indications for
      paraesophageal hernia repair have changed, and currently symptomatic
      paraesophageal hernias are recommended for repair. In addition, it is important
      not to overlook iron-deficiency anemia and pulmonary complaints, which tend to
      improve with repair. Current practice favors a laparoscopic approach, complete
      sac excision, primary crural repair with or without use of mesh, and a routine
      fundoplication.

PMID- 25941677
TI  - Contemporary options for restoration of anterior teeth with composite.
AB  - The present article gives an overview of modern adhesive restoration in the
      anterior area, in view of the fact that modern dental therapy should be as
      minimally invasive as possible. Illustrated with multiple cases, the article
      shows possible prospective fields of indication. 

PMID- 25941678
TI  - Clinical applications of cone beam computed tomography in endodontics: A
      comprehensive review.
AB  - Cone beam computed tomography (CBCT) is a new technology that produces three
      dimensional (3D) digital imaging at reduced cost and less radiation for the
      patient than traditional CT scans. It also delivers faster and easier image
      acquisition. By providing a 3D representation of the maxillofacial tissues in a
      cost- and dose-efficient manner, a better preoperative assessment can be obtained
      for diagnosis and treatment. This comprehensive review presents current
      applications of CBCT in endodontics. Specific case examples illustrate the
      difference in treatment planning with traditional periapical radiography versus
      CBCT technology. 

PMID- 25941679
TI  - Periodontal management of a patient with severe psoriasis: A case report.
AB  - Psoriasis is a common, disfiguring and stigmatizing skin disease associated with
      impaired quality of life. In patients with severe psoriasis unresponsive to other
      treatments, cyclosporine can induce a rapid remission. Although drug-induced
      gingival overgrowth (GO) is a frequent side effect, in the guidelines for the use
      of cyclosporine for psoriasis regular dental examinations were not mentioned as
      an essential part of monitoring of these patients. CASE REPORT: A 59-year-old man
      with GO involving almost all the interdental papillae (Seymour's grading score 1
      5) reported difficulties in mastication and gingival swelling. The medical
      history revealed severe recalcitrant psoriasis treated by oral cyclosporine. The
      periodontal treatment consisted of strict oral hygiene instructions, scaling,
      root surface instrumentation, and a 2-month interval periodontal supportive
      treatment. At 12 months an almost complete regression of GO was observed. A
      careful nonsurgical periodontal treatment combined with meticulous self-performed
      oral hygiene may avoid the need for surgical intervention, even in advanced
      cases.

PMID- 25941680
TI  - Nonsurgical treatment of recurrent gingival pyogenic granuloma: A case report.
AB  - Gingival pyogenic granuloma is a relatively common benign form of mucocutaneous
      lesion. Although surgical excision is considered to be the standard care, several
      reports have demonstrated a high recurrence rate of the lesion. In this case
      report a nonsurgical protocol to treat recurring gingival pyogenic granuloma and
      prevent further recurrence is suggested. The protocol includes strict oral
      hygiene instructions, scaling, root planing, and maintenance treatment. To the
      best of our knowledge, this is the first report of conservative nonsurgical
      management of recurrent gingival pyogenic granuloma lesions. 

PMID- 25941681
TI  - NaYF4:Yb,Er-MoS2: from synthesis and surface ligand stripping to negative
      infrared photoresponse.
AB  - The synthesis, surface ligand stripping, and infrared optoelectronic device
      application of NaYF4:Yb,Er-MoS2 nanocomposites are reported. NaYF4:Yb,Er-MoS2
      film shows an unusual negative infrared photoresponse after SOCl2/DMF treatment,
      which exhibits more than two times the photoresponsivity of pure NaYF4:Yb,Er,
      showing great potential for the development of novel infrared optoelectronic
      devices. 

PMID- 25941682
TI  - Irreversible structural change of a dry ionic liquid under nanoconfinement.
AB  - Studies of 1-hexyl-3-methyl-imidazolium ethylsulfate ([HMIM] EtSO4) using an
      extended surface forces apparatus show, for the first time, an ordered structure
      within the nanoconfined ionic liquid (IL) between mica surfaces that extends up
      to ~60 nm from the surface. Our measurements show the growth of this ordered IL
      film upon successive nanoconfinements-the structural changes being irreversible
      upon removal of the confinement-and the response of the structure to shear. The
      compressibility of this system is lower than that typically measured for ILs,
      while creep takes place during shear, both findings supporting a long-range
      liquid-to-solid transition. AFM (sharp-tip) studies of [HMIM] EtSO4 on mica only
      reveal ~2 surface IL-layers, with order extending only ~3 nm from the surface,
      indicating that confinement is required for the long-range IL-solidification to
      occur. WAXS studies of the bulk IL show a more pronounced ordered structure than
      is the case for [HMIM] with bis(trifluoromethylsulfonyl)imide as anion, but no
      long-range order is detected, consistent with the results obtained with the sharp
      AFM tip. These are the first force measurements of nanoconfinement-induced long
      range solidification of an IL. 

PMID- 25941683
TI  - A kinetic and thermochemical database for organic sulfur and oxygen compounds.
AB  - Potential energy surfaces and reaction kinetics were calculated for 40 reactions
      involving sulfur and oxygen. This includes 11 H2O addition, 8 H2S addition, 11
      hydrogen abstraction, 7 beta scission, and 3 elementary tautomerization
      reactions, which are potentially relevant in the combustion and desulfurization
      of sulfur compounds found in various fuel sources. Geometry optimizations and
      frequencies were calculated for reactants and transition states using
      B3LYP/CBSB7, and potential energies were calculated using CBS-QB3 and CCSD(T)
      F12a/VTZ-F12. Rate coefficients were calculated using conventional transition
      state theory, with corrections for internal rotations and tunneling.
      Additionally, thermochemical parameters were calculated for each of the compounds
      involved in these reactions. With few exceptions, rate parameters calculated
      using the two potential energy methods agreed reasonably, with calculated
      activation energies differing by less than 5 kJ mol(-1). The computed rate
      coefficients and thermochemical parameters are expected to be useful for kinetic
      modeling. 

PMID- 25941684
TI  - Construction of flexible photoelectrochemical solar cells based on ordered
      nanostructural BiOI/Bi2S3 heterojunction films.
AB  - Ordered 2D nanostructural BiOI nanoflake arrays decorated with Bi2S3 nanospheres
      have been designed and in situ fabricated for the first time, to form BiOI/Bi2S3
      bulk heterojunctions through a soft chemical route. A modified successive ionic
      layer adsorption and reaction (SILAR) method was developed to fabricate BiOI
      nanoflake arrays on flexible ITO/PET substrates at room temperature. The degree
      of transformation of BiOI to Bi2S3 was controlled through the adjustment of
      exposure time of the BiOI/ITO substrate to thioacetamide (TAA) aqueous solution.
      The morphologies of BiOI, BiOI/Bi2S3 heterojunctions and Bi2S3 films were
      examined by scanning electron microscopy (SEM), X-ray powder diffraction (XRD)
      patterns, and high resolution transmission electron microscopy (HRTEM). The
      presence of Bi2S3 was further validated through Raman spectroscopy and X-ray
      photoelectron spectroscopy (XPS). Especially, photoelectrochemical measurements
      demonstrated that such a Bi2S3 decorated BiOI photoanode based cell exhibits
      significant augments of short-circuit current density (Jsc) and incident photon
      to-current conversion efficiency (IPCE, 3 times higher than the pure BiOI
      photoanode), attributable to the stronger photo-absorption and better
      photogenerated charge carrier separation and transport efficiency. The surface
      photovoltage (SPV) measurements further confirmed the importance of BiOI/Bi2S3
      heterojunctions in such PEC cells. This solution-based process directly on
      flexible ITO offers the promise for low-cost, large-area, roll-to-roll
      application of the manufacturing of the third generation thin-film photovoltaic
      devices. 

PMID- 25941685
TI  - Proceedings of the 12th International Congress of Inborn Errors of Metabolism,
      3rd-6th September, 2013, Barcelona, Spain.

PMID- 25941686
TI  - Special issue dedicated to John H Laragh.

PMID- 25941687
TI  - Proceedings of the 15th International Congress on Neutron Capture Therapy Impact
      of a New Radiotherapy Against Cancer, 23 August 2005,  Tsukuba, Japan.

PMID- 25941688
TI  - Special issue dedicated to John G. Bartlett.

PMID- 25941690
TI  - Proceedings of the 5th ILSI International Symposium on Food Packaging, 14-16
      November, 2012, Berlin, Germany.

PMID- 25941689
TI  - Special issue in in honour of Balazs Gyorffy.

PMID- 25941691
TI  - Special issue dedicated to James S Hyde.

PMID- 25941692
TI  - Interview with Dr Jerome H Jaffe.

PMID- 25941693
TI  - The case for medical marijuana: an issue of relief.

PMID- 25941694
TI  - Legalizing marijuana for medical purposes will increase risk of long-term,
      deleterious consequences for adolescents.

PMID- 25941695
TI  - Preconceptions based on drug origin.

PMID- 25941696
TI  - Vemurafenib (Zelboraf) with longer follow-up. Metastatic melanoma: a few extra
      months of life, but many adverse effects.
AB  - Further analysis of the unblinded trial described in the initial clinical
      evaluation suggests that vemurafenib prolongs survival by a median of about 4
      months compared with dacarbazine. The adverse effects of vemurafenib are frequent
      and sometimes serious. More data are needed on renal and pancreatic toxicity and
      the risk of extracutaneous cancers.

PMID- 25941697
TI  - Subcutaneous trastuzumab (Herceptin). Ready to use, but more serious adverse
      effects than intravenous (IV) trastuzumab.

PMID- 25941698
TI  - Diacerein. A controversial EU re-evaluation upholds marketing authorisation,
      unfortunately.
AB  - Some national health authorities were in favour of market withdrawal of
      diacerein, a "slow-acting symptomatic" treatment for osteoarthritis, because of a
      disproportionate risk of adverse effects.

PMID- 25941699
TI  - Kaneuron: an oral solution of phenobarbital with dangerous packaging.
AB  - The syringe with dual graduations has been eliminated following cases of overdose
      in children, but there is still no child-proof cap.

PMID- 25941700
TI  - Ipilimumab (Yervoy) and inoperable or metastatic melanoma. More evaluation
      needed, in both first- and second-line use.

PMID- 25941701
TI  - Topical minoxidil: accidental poisoning in children.
AB  - Hypotension and persistent tachycardia in a young girl after ingesting minoxidil
      cutaneous solution intended for her father.

PMID- 25941702
TI  - Acute kidney injury due to drug-induced hypersensitivity.
AB  - Many drugs such as vitamin K antagonists, antibiotics, NSAIDs, and proton pump
      inhibitors can cause acute kidney injury through hypersensitivity.These reactions
      are rare but serious. Discontinuation of the drug must be arranged as soon as
      possible.

PMID- 25941703
TI  - Weekly methotrexate: harmful to exposed embryos.

PMID- 25941704
TI  - Ambroxol, bromhexine: anaphylactic reactions.

PMID- 25941705
TI  - Growth hormone: brain haemorrhage.

PMID- 25941706
TI  - Mammographic breast cancer screening. Part II. Non-randomised comparisons:
      results similar to those of randomised trials.
AB  - Screening practices in the early 21st century may not have the same impact on
      breast cancer mortality than the small reduction seen in some randomised
      controlled trials. To determine whether non-randomised comparative studies can
      help to estimate the possible benefits of mass screening for breast cancer, we
      conducted a review of the literature using the standard Prescrire methodology.
      The most reliable non-randomised studies are those that combine historical and
      geographic comparisons, include follow-up data recorded for at least 10 years
      after the introduction of screening, and take into account the date of cancer
      diagnosis in mortality calculations. We identified eight such studies, all
      conducted in Scandinavian countries, in regions where screening was generally
      introduced during the 1980s and 1990s. Three studies conducted in Sweden showed
      no statistically significant reduction in all-cause mortality among women with
      breast cancer after the introduction of screening. One of the two Finnish studies
      (statistically the most powerful) and a Danish study showed a statistically
      significant decrease in breast cancer mortality after the introduction of
      screening. A study conducted in four Norwegian counties showed no significant
      reduction in breast cancer mortality after the introduction of screening. A meta
      analysis of five of these studies, corresponding to a total of about 4.7 million
      woman-years, showed that the introduction of organised breast cancer screening
      among women aged 50 to 69 years was associated with about a one-sixth reduction
      in breast cancer mortality. Another study, published after this meta-analysis,
      was conducted throughout Norway and spanned more than 15 million woman-years. It
      showed that the introduction of organised screening was associated with about a
      one-quarter reduction in mortality attributed to breast cancer, equivalent to
      about 20 to 30 fewer breast cancer deaths per 10 000 women invited for screening.
      Overall, the results of these different studies are consistent with the small
      decrease in breast cancer mortality observed in randomised trials and their least
      stringent meta-analyses. This rather modest benefit must be weighed against the
      adverse effects of screening and treatment, which will be examined in a future
      issue.

PMID- 25941707
TI  - Identifying the least biased studies.

PMID- 25941708
TI  - Hypoglycaemic therapy in type 2 diabetes. Part I. Metformin is the only glucose
      lowering drug known to prevent complications of diabetes.
AB  - Metformin monotherapy appears to reduce mortality in patients with type 2
      diabetes, with generally acceptable adverse effects. To determine whether any
      other glucose-lowering drugs have been shown to prevent or delay the onset of
      long-term clinical complications of diabetes, we conducted a systematic review of
      the literature using the standard Prescrire methodology. We identified only six
      randomised controlled trials, versus placebo or no treatment, that were designed
      to evaluate the efficacy of glucose-lowering drugs in preventing the clinical
      complications of type 2 diabetes. Three trials of various insulins failed to
      demonstrate a tangible benefit for patients with type 2 diabetes and moderate
      hyperglycaemia. In one trial, cardiovascular mortality appeared to be higher in
      the group treated with tolbutamide, a glucose-lowering sulphonylurea. In a trial
      lasting 11 years, another sulphonylurea, glibenclamide, appeared to reduce the
      incidence of diabetes complications, but it had no impact on mortality. The
      results of this trial are undermined by methodological flaws. In trials lasting
      up to 3 years, pioglitazone, alogliptin and saxagliptin had no effect in
      preventing the clinical complications of diabetes in patients with relatively
      high blood glucose levels. * In 2014, metformin is the only hypo- glycaemic drug
      that appears to reduce mortality among patients with type 2 diabetes in
      comparative trials. Compa- rative data suggesting that gliben- clamide prevents
      some complications of diabetes are rather unconvincing. No other glucose-lowering
      drugs have been shown to prevent the complica- tions of diabetes, but their
      evaluation is inadequate.

PMID- 25941709
TI  - Types of glucose-lowering drugs and their mechanisms of action.

PMID- 25941710
TI  - New drugs and indications in 2014. Some advances this year, but many drugs are
      poorly evaluated, too expensive, or more dangerous than useful.
AB  - Three drugs analysed by Prescrire in 2014 provided a significant therapeutic
      advance for some patients. In 2014, too many drugs are still best avoided, have
      undergone minimal evaluation, or are excessively expensive. Drug regulatory
      agencies should continue their efforts to improve pharmacovigilance and
      transparency.

PMID- 25941711
TI  - No-gift policy in medical schools. Demonstrated impact on prescribing behaviour.
AB  - A study has shown that a policy banning pharmaceutical industry gifts in US
      medical schools has beneficial effects on prescribing behaviour once students
      enter clinical practice.

PMID- 25941712
TI  - [Antiadhesive properties of the surfactants of Acinetobacter calcoaceticus IMB B
      7241, Rhodococcus erythropolis IMB Ac-5017, and Nocardia vaccinii IMB B-7405].
AB  - Attachment of the cells of some bacteria, yeasts, and micromycetes to various
      surfaces (catheters, dentures, plastic, polyvinyl chloride, tiles, and steel)
      treated with the surfactants fromAcinetobacter calcoace- ticus IMB B-7241,
      Rhodococcus erythropolis IMB Ac-5017, and Nocardia vaccinii IMB B-7405 was
      studied. Adhesion of microorganisms to all the studied surfaces depended on the
      surfactant concentration and purity, kind of surface, and the test culture.
      Treatment with the surfactants from N. vaccinii IMB B-7405 (0.005- 0.05 mg/mL),
      A. calcoaceticus IMB B-7241 (0.003-0.036 mg/mL), and R. erythropolis IMB Ac-5017
      (0.03- 0.12 mg/mL) resulted in adhesion decreased respectively by 35-75, 60-75,
      and 25-90% for bacteria (Es- cherichia coli IEM-1, Bacillus subtilis BT-2, etc.),
      by 80-85, 55-90, and 15-60% for yeasts Candida albicans D-6, and by 40-50, 35-45,
      and 10-20% for micromycetes (Aspergillus niger P-3 and Fusarium culmorum T-7).

PMID- 25941713
TI  - [Effect of alkylresorcinols on thermal denaturation and refolding of bacterial
      luciferase and synthesis of heat shock proteins revealed in the luminescent
      molecular and cellular test systems].
AB  - Molecular and cellular luminescent biotests were used to reveal the effects of
      five alkylresorcinol homologues (C7-, C9-, C11-, C12-, and C18-AR) on the
      thermally induced denaturation and refolding ofbac- terial luciferases, as well
      as on the synthesis of heat shock proteins. The ARs activities were found to
      depend on their fine structure and concentration. Direct heat-protective effect
      of short-chain C7- and C9-AR on the chromatographically pure Photobactrium
      leiognathii luciferase/oxidoreductase was shown within broad range of
      concentration (10(-6)-10(-3) M). The long-chain ARs homologues exhibited a
      similar heat-protective effect at micromolar concentrations only, while their
      millimolarconcentrations have increased the sensitivity of the model proteins to
      thermal treatment. The recombinant strain Escherichia coli K12 MG1655 bearing
      constitutively expressed Vibrio fischieri luxAB genes was used to investigate
      theARs effect on the intracellular chaperone-independent refolding of bacterial
      luciferase. The functional activity of heat-inactivated enzyme was restored by
      micromolar concentrations of short-chain ARs, while long-chain homologues
      inhibited re- folding in the wide concentration range. The recombinant
      luminescent E. coli strain bearing the inducible ib- pA'::luxCDABE genetic
      construction was used to determine the effect of ARs on the synthesis of heat
      shock proteins (HSP). The preincubation mode of bacterial cells with long-chain
      alkylresorcinols led to dose-de- pendent stimulation of HSP synthesis (2.7 to 4
      times) that confirmed some ARs function as "alarmones". Subsequent thermal
      treatment resulted in a 5-15-fold decrease of the following HSP induction
      compared to the control, while the number of viable cells opposite increased 1.5
      4-fold. Thus, pretreatment of the bacte- rial cells with long-chain ARs resulted
      in their preadaptation to subsequent thermally induced stress. Short- chainARs
      caused less pronounced HSP suppression, although still was accompanied by
      increased heat resis- tance of the AR-pretreated bacterial cells.

PMID- 25941714
TI  - [Fungicidal properties of the nanosystems of silkworm (Bombyx mor) chitosan with
      copper ions].
AB  - The fungicidal activity of some chitosan samples and of its nanostructured
      systems with copper was studied. The samples of Bombyx mori chitosan and its
      nanostructured systems with copper were found to inhibit growth and development
      of phytopathogenic fungi Fusarium solani 169 and Verticillium dahlie 57. The
      growth inhibition zone was of considerable size (22 to 60 mm).

PMID- 25941715
TI  - [Characterization of Pantoea agglomerans lipopolysaccharides].
AB  - Lipopolysaccharides (LPS) from seven Pantoea agglomerans strains isolated from
      various plants were purified and chemically identified. LPS of the studied P.
      agglomerans strains were heterogeneous in monosaccharide composition. Thus, the
      LPS of P. agglomerans 8606 differed considerably from the LPSs of other strains,
      containing mannose as the predominant monosaccharide (69.8%), as well as ribose
      (15.1%) and xylose (12.6%), while the content of rhamnose, one of the predominant
      monosaccharides in other LPS samples, was 2.5%. Analysis of the fatty acid
      composition revealed the presence of C12-C16 acids. In lipids A of all the
      studied strains, 3-OH-C14:0 was the predominant acid (31.7 to 39.1%, depending on
      the strain). C12:0 (8.2 to 31.5%), C14:0 (12.9 to 30.8%), and C16:0 acids (3.4 to
      16.9%) were also revealed. The studied P. agglomerans strains fell into three
      groups according to their fatty acid composition. The differences stemmed from
      the presence or absence of two fatty acids, 2-OH-C14:0 and C16:1. Ouchterlony
      double immunodiffusion in agar revealed that all the LPS under study exhibited
      antigenic activity in homologous systems. The results of serological cross
      reactions indicated immunochemical heterogeneity of the species P. agglomerans.
      Comparative investigation of the complex of parameters of peripheral blood cells
      from a healthy donor before and after treatment with LPS solutions showed that
      the values of no parameters exceeded the normal range.

PMID- 25941716
TI  - [Hydrocarbon-Oxidizing potential and the genes for n-alkane biodegradation in a
      new acidophilic mycobacterial association from sulfur blocks].
AB  - Capacity of AG(S10), a new aerobic acidophilic (growing within the pH range from
      1.3 to 4.5 with the optimum at 2.0-2.5) bacterial association from sulfur blocks
      of the Astrakhan gas-processing complex (AGC), for oxidation of hydrocarbons of
      various chemical structure was investigated. A broad spectrum of normal (C10-C21)
      and iso-alkanes, toluene, naphthalene, andphenanthrene, as well as isoprenoids
      resistant to microbial degradation, pristane and phytane (components of paraffin
      oil), and 2,2,4,4,6,8,8,-heptamethylnonane, a branched hydrocarbon, were
      biodegraded under acidic conditions. Microbiological investigation revealed the
      dominance of mycobacteria in the AGS10 association, which was confirmed by
      analysis of the 16S rRNA gene clone library. In the phylogenetic tree, the 16S
      rRNA sequences formed a branch within the cluster of slow-growing mycobacteria,
      with 98% homology to the closest species Mycobacterium florentinum. Genomic DNA
      of AG(S10) culture grown on C14-C17 n-alkanes at pH 2.5 was found to contain the
      genes of two hydroxylase families, alkB and Cyp 153, indicating their combined
      involvement in hydrocarbon biodegradation. The high hydrocarbon-oxidizing
      potential of the AGS10 bacterial association, indicated that further search for
      the genes responsible for degradation of various hydrocarbons in acidophilic
      mycobacteria could be promising.

PMID- 25941717
TI  - [Finding of dairy yeasts Kluyveromyces lactis var. lactis in natural habitats].
AB  - Well-known yeasts Kluyveromyces lactis var. lactis, which are usually associated
      with dairy prod- ucts, were discovered in nature (in woodland park soil under
      Impatiens glandulifera Royle plants). Reliable identification of the yeasts was
      carried out using physiological criteria (lactose and maltose utilization) and
      molecular markers (nucleotide sequence of the 5.8S-ITS rDNA fragment, pulsed
      field electrophoresis, and Southern hybridization of chromosomal DNA with the
      LAC4 probe). Ecology of KI. lactis var. lactis is discussed.

PMID- 25941718
TI  - [Analysis of bacterial communities of two Lake Baikal endemic sponge species].
AB  - Bacterial diversity of two Lake Baikal endemic sponges characterized by different
      life forms, branching Lubomirskia baicalensis and cortical Baikalospongia sp.,
      was studied using the method of 454 pyrosequencing of the 16S rRNA gene
      fragments. In the communities associated with L. baicalensis and Baikalospongia
      sp., 426 and 428 OTUs, respectively, were identified. In microbial associations
      of these spong- es, 24 bacterial phyla were identified, with predominance of
      Bacteroidetes, Proteobacteria, and Actinobacteria. Analysis of the taxonomic
      composition of bacterial communities of the sponges was carried out by search of
      the dominant phylotypes within the phylum level cluster. Comparison of bacterial
      associations of the sponges with Lake Baikal bacterioplankton revealed both the
      shared OTUs and the unique ones characteristic of the studied species.

PMID- 25941719
TI  - [Production of gaseous hydrocarbons by microbial communities of Lake Baikal
      bottom sediments].
AB  - Production of gaseous hydrocarbons by the microbial community of the Posolsky
      Bank methane seep bottom sediments (Southern Baikal) was studied at 4 degrees C.
      Formation of both methane and a heavier gas- eous hydrocarbon, ethane, was
      detected in enrichment cultures. The highest methane concentrations (6.15 and
      4.51 mmol L(-1)) were revealed in enrichments from the sediments from 55-cm depth
      incubated with-so- dium acetate and H2/CO2 gas mixture, respectively. A decrease
      in activity of aceticlastic methanogensand a decrease in methane concentration
      produced by hydrogenotrophic archaea occurred with depth. The highest
      concentration of ethane was revealed in enrichments from the microbial community
      of the layer close to gas hydrates (75 cm) incubated with CO2 as a substrate.
      According to analysis of the 16S rRNA gene fragments from the clone library,
      these enrichments were found to contain members of the phylum Crenarchaeota form-
      ing a separate cluster with members of the class Thermoprotei. The phylum
      Euryarchaeota was represented by nucleotide sequences of the organisms homologous
      to members of the orders Methanococcales, Methanosa- rcinales, and
      Thermoplasmatales.

PMID- 25941720
TI  - [Occurrence of the SAL+ phenotype in soil pseudomonads].
AB  - Genetic systems of salicylate catabolism were studied in 75 strains of
      fluorescent pseudomoriads and in 30 exogenously isolated SAL plasmids. All
      exogenously isolated SAL plasmids were found to contain the classical nahG gene
      in combination with the genes of the meta-pathway of catechol cleavage. In most
      studied strains, salicylate catabolism was controlled by the chromosomal genes,
      the nah Ugene being the key gene ofsalicylate utilization and subsequent catechol
      cleavage occurring via the ortho-pathway. It is suggested that the nah U-like
      sequences play a key role in occurrence of the Sal+ phenotype in strains
      degrading salicylate, but not naphthalene.

PMID- 25941721
TI  - [Effect of mechanical grinding of Sphagnum on the structure and physiological
      state of bacterial communities].
AB  - The microcosm method was used to demonstrate an increase in bacterial numbers and
      drastic changes in the taxonomic structure of saprotrophic bacteria as a result
      of mechanical grinding of Sphagnum moss. Ekkrisotrophic agrobacteria predominant
      in untreated moss were replaced by hydrolytic bacteria. Molecular biological
      approaches revealed such specific hydrolytic bacteria as Janthinobacterium
      agaricum and Streptomyces purpurascens among the dominant taxa. The application
      of kinetic technique for determination of the physiological state of bacteria in
      situ revealed higher functional diversity of hydrolytic bacteria in ground moss
      than in untreated samples. A considerable decrease of the C/N ratio in ground
      samples of living Sphagnum incubated using the microcosm technique indicated
      decomposition of this substrate.

PMID- 25941722
TI  - [Microbial community of the bottom sediments of the brackish Lake Beloe
      (Transbaikal region)].
AB  - Investigation of microbial taxonomic diversity and of the rates of microbial
      processes of production and decomposition of organic matter made it possible to
      establish considerable diversity and activity of the sulfur cycle microorganisms
      in the microbial community of Lake Beloe (pH 9.4, salinity 3.1 g/L) upper
      sediment layer. According to the results of pyrosequencing, of the 16S rRNA gene,
      bacteria involved in H2 formation and oxidation were numerically predominant and
      highly diverse. The Hydrogenophaga spp. dominating in the community are aerobic
      or facultatively anaerobic chemoorgano- and chemolithoautotrophs using hydrogen
      oxidation as the source of energy. They play an important role in the transitory
      zones of mixing of subterranean and surface water.

PMID- 25941723
TI  - [Phylogenetic diversity of bacteria in soda lake stratified sediments].
AB  - Various previously developed techniques for DNA extraction from the samples with
      complex physicochemical structure (soils, silts, and sediments) and modifications
      of these techniques developed in the present work were tested. Their usability
      for DNA extraction from the sediments of the Kulunda Steppe hypersaline soda
      lakes was assessed, and the most efficient procedure for indirect (two-stage) DNA
      extraction was proposed. Almost complete separation of the cell fraction was
      shown, as well as the inefficiency of nested PCR for analysis of the clone
      libraries obtained from washed sediments by amplification of the 16S rRNA gene
      fragments. Analysis of the clone library obtained from the cell fractions of
      stratified sediments (upper, medium, and lower layers) revealed that in the
      sediments of Lake Gorchina-3 most eubacterial phylotypes belonged to the class
      Clostridia, phylum Firmicutes. They were probably specific for this habitatand
      formed a new, presently unknown high-rank taxon. The data obtained revealed no
      pronounced stratification of the spe- cies diversity of the eubacterial component
      of the microbial community inhabiting the sediments (0-20 cm) in the inshore zone
      of Lake Gorchina-3.

PMID- 25941724
TI  - [Capacity of hyperthermophilic Crenarchaeota for decomposition of refractory
      protiens (alpha- and beta-keratins)].
AB  - Anaerobic thermophilic archaea of the genera Thermogladius and Desulfurococcus
      capable of a- and P3-keratin decomposition were isolated from hot springs of
      Kamchatka and Kunashir Island. For two of them (strains 2355k and 3008g), the
      presence of high-molecular mass, cell-bound endopeptidases active against
      nonhydrolyzed and partially hydrolyzed proteins at high values of temperature and
      pH was shown. Capacity for beta-keratin decomposition was also found in
      collection strains (type strains of Desulfurococcus amylolyticus subsp.
      amylolyticus, D. mucosus subsp. mobilis, and D. fermentans).

PMID- 25941725
TI  - Erich Walther Six (1926-2014): discoverer of the satellite phage P4.

PMID- 25941726
TI  - INN common stem: -rafenib.

PMID- 25941727
TI  - Implementing culturally competent care.

PMID- 25941728
TI  - Author response.

PMID- 25941729
TI  - Author response.

PMID- 25941730
TI  - Drug used to treat diabetes may get ok for weight loss.

PMID- 25941731
TI  - ACA rule review targets out-of-pocket cost calculation.

PMID- 25941732
TI  - Urgent care finds its place in the age of ACOs.

PMID- 25941733
TI  - An accounting of ACOs.

PMID- 25941734
TI  - The tortoise and the hare.

PMID- 25941735
TI  - As goes South Dakota so goes the country?

PMID- 25941736
TI  - Specialty agents with expedited approval may fuel 2015 pharmacy costs.

PMID- 25941737
TI  - Docs ill-equipped to evaluate genetic variant data.

PMID- 25941738
TI  - MA plan excels in tough neighborhoods.

PMID- 25941739
TI  - An Aryl Hydrocarbon Receptor from the Salamander Ambystoma mexicanum Exhibits Low
      Sensitivity to 2,3,7,8-Tetrachlorodibenzo-p-dioxin.
AB  - Structural features of the aryl hydrocarbon receptor (AHR) can underlie species-
      and population-specific differences in its affinity for 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD). These differences often explain variations in
      TCDD toxicity. Frogs are relatively insensitive to dioxin, and Xenopus AHRs bind
      TCDD with low affinity. Weak TCDD binding results from the combination of three
      residues in the ligand-binding domain: A354 and A370, and N325. Here we sought to
      determine whether this mechanism of weak TCDD binding is shared by other
      amphibian AHRs. We isolated an AHR cDNA from the Mexican axolotl (Ambystoma
      mexicanum). The encoded polypeptide contains identical residues at positions that
      confer low TCDD affinity to X. laevis AHRs (A364, A380, and N335), and homology
      modeling predicts they protrude into the binding cavity. Axolotl AHR bound one
      tenth the TCDD of mouse AHR in velocity sedimentation analysis, and in
      transactivation assays, the EC50 for TCDD was 23 nM, similar to X. laevis
      AHR1beta (27 nM) and greater than AHR containing the mouse ligand-binding domain
      (0.08 nM). Sequence, modeled structure, and function indicate that axolotl AHR
      binds TCDD weakly, predicting that A. mexicanum lacks sensitivity toTCDD
      toxicity. We hypothesize that this characteristic of axolotl and Xenopus AHRs
      arose in a common ancestor of the Caudata and Anura. 

PMID- 25941740
TI  - Membrane permeation of a peptide: it is better to be positive.
AB  - A joint experimental and computational study investigates the translocation of a
      tryptophan molecule through a phospholipid membrane. Time dependent spectroscopy
      of the tryptophan side chain determines the rate of permeation into 150 nm
      phospholipid vesicles. Atomically detailed simulations are conducted to calculate
      the free energy profiles and the permeation coefficient. Different charging
      conditions of the peptide (positive, negative, or zwitterion) are considered.
      Both experiment and simulation reproduce the qualitative trend and suggest that
      the fastest permeation is when the tryptophan is positively charged. The
      permeation mechanism, which is revealed by molecular dynamics simulations, is of
      a translocation assisted by a local defect. The influence of long-range
      electrostatic interactions, such as the membrane dipole potential on the
      permeation process, is not significant. 

PMID- 25941741
TI  - Long-Term n-Caproic Acid Production from Yeast-Fermentation Beer in an Anaerobic
      Bioreactor with Continuous Product Extraction.
AB  - Multifunctional reactor microbiomes can elongate short-chain carboxylic acids
      (SCCAs) to medium-chain carboxylic acids (MCCAs), such as n-caproic acid.
      However, it is unclear whether this microbiome biotechnology platform is stable
      enough during long operating periods to consistently produce MCCAs. During a
      period of 550 days, we improved the operating conditions of an anaerobic
      bioreactor for the conversion of complex yeast-fermentation beer from the corn
      kernel-to-ethanol industry into primarily n-caproic acid. We incorporated and
      improved in-line, membrane liquid-liquid extraction to prevent inhibition due to
      undissociated MCCAs at a pH of 5.5 and circumvented the addition of methanogenic
      inhibitors. The microbiome accomplished several functions, including hydrolysis
      and acidogenesis of complex organic compounds and sugars into SCCAs, subsequent
      chain elongation with undistilled ethanol in beer, and hydrogenotrophic
      methanogenesis. The methane yield was 2.40 +/- 0.52% based on COD and was limited
      by the availability of carbon dioxide. We achieved an average n-caproate
      production rate of 3.38 +/- 0.42 g L(-1) d(-1) (7.52 +/- 0.94 g COD L(-1) d(-1))
      with an n-caproate yield of 70.3 +/- 8.81% and an n-caproate/ethanol ratio of
      1.19 +/- 0.15 based on COD for a period of ~55 days. The maximum production rate
      was achieved by increasing the organic loading rates in tandem with elevating the
      capacity of the extraction system and a change in the complex feedstock batch. 

PMID- 25941742
TI  - Nutritional Risk Screening Predicts Tumor Response in Lung Cancer Patients.
AB  - BACKGROUND: Malnutrition in cancer patients may be associated with poor tolerance
      of chemotherapy and lower response rate after oncological treatment. METHODS:
      Nutritional Risk Screening 2002 (NRS) adapted for oncological patients was used
      to assess the risk of undernutrition in a group of 188 patients with lung cancer.
      The risk was evaluated on a 6-point scale according to common signs of
      nutritional status (weight loss, body mass index, and dietary intake), tumor, and
      its treatment risk factors. A score of 3 or more (called "nutritional risk")
      means significant risk of malnutrition and poor outcome. RESULTS: Acceptable NRS
      score was found in 50.6%, and in 45.3% a score of 3-5 suggested the risk of
      malnutrition (nutritional risk). Unexpectedly, the toxicity of anticancer
      treatment was not significantly different between the subgroups (acceptable score
      vs nutritional risk). The rate of treatment response evaluated by imaging
      techniques was significantly higher in patients with an acceptable score compared
      to nutritional risk. Overall survival rate was significantly higher in
      cytostatically treated patients with lung cancer with an acceptable score.
      CONCLUSION: Nutritional risk screening is a significant predictor of tumor
      response in patients with lung cancer. Early detection of malnutrition is
      important to determine the prognosis of cancer patients as well as to plan
      effective supportive care.

PMID- 25941743
TI  - Rectifying Single GaAsSb Nanowire Devices Based on Self-Induced Compositional
      Gradients.
AB  - Device configurations that enable a unidirectional propagation of carriers in a
      semiconductor are fundamental components for electronic and optoelectronic
      applications. To realize such devices, however, it is generally required to have
      complex processes to make p-n or Schottky junctions. Here we report on a
      unidirectional propagation effect due to a self-induced compositional variation
      in GaAsSb nanowires (NWs). The individual GaAsSb NWs exhibit a highly
      reproducible rectifying behavior, where the rectifying direction is determined by
      the NW growth direction. Combining the results from confocal micro-Raman
      spectroscopy, electron microscopy, and electrical measurements, the origin of the
      rectifying behavior is found to be associated with a self-induced variation of
      the Sb and the carrier concentrations in the NW. To demonstrate the usefulness of
      these GaAsSb NWs for device applications, NW-based photodetectors and logic
      circuits have been made. 

PMID- 25941744
TI  - A new ent-kaurane diterpenoid from Ixora amplexicaulis.
AB  - A new ent-kaurane diterpenoid, 6alpha,16alpha-dihyroxy-ent-kaurane (1), was
      isolated from the stems of Ixora amplexicaulis, together with (24R)-6beta-hydroxy
      24-ethyl-cholest-4-en-3-one (2), 7beta-hydroxysitosterol (3), maslinic acid (4),
      3,3'-bis(3,4-dihydro-4-hydroxy-6-methoxy-2H-1-benzopyran) (5) and protocatechuric
      acid (6). Their structures were established by extensive spectroscopic analysis,
      including 2D NMR techniques. Compounds 2-5 were isolated from the genus Ixora for
      the first time and 6 obtained originally from I. amplexicaulis. 

PMID- 25941745
TI  - Understanding Mammalian Germ Line Development with In Vitro Models.
AB  - Germ line development is crucial in organisms with sexual reproduction to
      complete their life cycle. In mammals, knowledge about germ line development is
      based mainly on the mouse model, in which genetic and epigenetic events are well
      described. However, little is known about how germ line development is
      orchestrated in humans, especially in the earliest stages. New findings derived
      from human in vitro models to obtain germ cells can shed light on these
      questions. This comprehensive review summarizes the current knowledge about
      mammalian germ line development, emphasizing the state of the art obtained from
      in vitro models for germ cell-like cell derivation. Current knowledge of the
      pluripotency cycle and germ cell specification has allowed different in vitro
      strategies to obtain germ cells with proven functionality in mouse models.
      Several reports during the last 10 years show that in vitro germ cell derivation
      with proven functionality to generate a healthy offspring is possible in mice.
      However, differences in the embryo development and pluripotency potential between
      human and mouse make it difficult to extrapolate these results. Further efforts
      on both human and mouse in vitro models to obtain germ cells from pluripotent
      stem cells may help to elucidate how human physiological events take place;
      therefore, therapeutic strategies can also be considered. 

PMID- 25941746
TI  - How religiosity shapes health perceptions and behaviors of Latina immigrants: is
      it an enabling or prohibitive factor?
AB  - The study examines how religiosity shapes the health perceptions and health
      related behaviors of 50 Latina immigrants from El Salvador, Guatemala, Mexico and
      Bolivia. Between May and August 2011, focus groups were conducted with
      participants representing each country of origin. Qualitative content analysis
      was the analytic strategy adopted in the study. The meta-theme, Religiosity
      Contributes to Positive Perceptions of Health and Health-Promoting Behaviors, is
      associated with six emerging themes: (1) Religiosity promotes a sense of personal
      responsibility for one's health; (2) Religiosity promotes a holistic view of
      health; (3) Religiosity promotes the view that health is a priority; (4)
      Religiosity promotes the view that health enables one to perform necessary tasks;
      (5) Religiosity promotes health-seeking behavior; and (6) Religiosity provides
      intrinsic health benefits. Findings do not follow the clear-cut dichotomy of the
      health locus of control model and challenge simplified notions that Latinas hold
      a purely external health locus of control toward their health and health care.
      Latinas rely on both God and themselves in managing their health and engaging in
      health-promoting actions, which are prompted in large part by their religiosity.
      Implications for culturally appropriate health communication and interventions
      are discussed. 

PMID- 25941747
TI  - Thiol-activated triplet-triplet annihilation upconversion: study of the different
      quenching effect of electron acceptor on the singlet and triplet excited states
      of Bodipy.
AB  - Thiol-activated triplet-triplet annihilation (TTA) upconversion was studied with
      two different approaches, i.e., with 2,4-dinitrobenzenenesulfonyl (DNBS)-caged
      diiodoBodipy triplet photosensitizers (perylene as the triplet acceptor/emitter
      of the upconversion) and DNBS-caged Bodipy fluorophore as the triplet
      acceptor/emitter (PdTPTBP as the triplet photosensitizer, TPTBP =
      tetraphenyltetrabenzoporphyrin). The photophysical processes were studied with
      steady-state UV-vis absorption spectroscopy, fluorescence spectroscopy,
      electrochemical characterization, nanosecond transient absorption spectroscopy,
      and DFT/TDDFT computations. DNBS-caged triplet photosensitizer shows a shorter
      triplet state lifetime (24.7 MUs) than the uncaged triplet photosensitizer (86.0
      MUs), and the quenching effect is due to photoinduced electron transfer (PET).
      TTA upconversion was enhanced upon cleavage of the DNBS moiety by thiols. On the
      other hand, the DNBS-caged Bodipy shows no fluorescence, but the uncaged
      fluorophore shows strong fluorescence; thus, TTA upconversion is able to be
      enhanced with the uncaged fluorophore as the triplet energy acceptor/emitter. The
      results indicate that the DNBS moiety exerts a significant quenching effect on
      the singlet excited state of Bodipy, but the quenching on the triplet excited
      state is much weaker. Calculation of the Gibbs free energy changes of the
      photoinduced electron transfer indicates that the singlet state gives a larger
      driving force for the PET process than the triplet state. 

PMID- 25941748
TI  - Partridgeberry polyphenols protect rat primary cortical neurons from oxygen
      glucose deprivation-reperfusion-induced injury via suppression of inflammatory
      adipokines and regulation of HIF-1alpha and PPARgamma.
AB  - OBJECTIVES: The aim of this study was to investigate the neuroprotective ability
      of partridgeberry polyphenols in rat primary cortical neurons against oxygen
      glucose deprivation/reperfusion (OGD/R) injury in vitro and explore the
      underlying therapeutic mechanism(s). METHODS: The OGD/R injury was induced in rat
      primary cortical neurons by incubation with deoxygenated glucose-free medium in a
      hypoxia chamber. RESULTS: The strongest activity in this regard was exhibited by
      partridgeberry-derived PPF2 and PPF3, i.e. the flavan-3-ol- and flavonol-rich
      polyphenol fractions of partridgeberry (P <= 0.05). Moreover, partridgeberry
      polyphenol pre-treatment reduced the membrane damage in primary neurons, as
      measured by the lactose dehydrogenase (LDH) release assay (P <= 0.05).
      Furthermore, PPF2 and PPF3 pre-treatment (100 ug ml(-1)) for 24 hours, before
      OGD/R, resulted in the strongest suppression of interleukin (IL)-6 and tumor
      necrosis factor-alpha induction by OGD/R injury, compared with the control group
      (P <= 0.05). Additionally, the protein levels of hypoxia-inducible factor (HIF
      1alpha) and PPARgamma, quantified by ELISA presented a significant modulation
      following PPFs treatment (100 ug ml(-1)), favorably toward neuroprotection,
      compared with the respective controls after OGD/R injury in vitro (P <= 0.05).
      CONCLUSION: In summary, partridgeberry polyphenols at concentrations of 1-100 ug
      ml(-1), significantly induced a decline in OGD/R injury-triggered apoptosis in
      vitro, suppressed the inflammatory biomarkers in primary neurons, and modulated
      the activity of HIF-1alpha and proliferator-activated receptor gamma (PPARgamma)
      following hypoxic injury.

PMID- 25941750
TI  - Transumbilical Single-Site Laparoscopic Inguinal Hernia Inversion and Ligation in
      Girls.
AB  - OBJECTIVES: The combination of transumbilical single-site laparoscopic inguinal
      hernia inversion and ligation is a new approach for girls. We have done 13 cases
      in our hospital since May 2013. MATERIALS AND METHODS: Thirteen girls with
      inguinal hernia, from 6 months to 10 years of age, were treated with
      transumbilical single-site laparoscopy. RESULTS: None of the patients underwent
      conversion from single-site laparoscopy to the open approach or conventional
      laparoscopic surgery. The average operation time was 35.15+/-6.68 minutes. Four
      cases were found to have a contralateral inguinal hernia. The patients were
      discharged the day after operation. Follow-up of 7 months to a year with all
      cases showed no recurrence and no incision complication. CONCLUSIONS: The
      combination of transumbilical single-site laparoscopic inguinal hernia inversion
      and ligation is a reliable, safe, and cosmetic herniorrhaphy for girls with
      inguinal hernia.

PMID- 25941749
TI  - Regulation of phagocytosis by Rho GTPases.
AB  - Phagocytosis is defined as a cellular uptake pathway for particles of greater
      than 0.5 MUm in diameter. Particle clearance by phagocytosis is of critical
      importance for tissue health and homeostasis. The ultimate goal of anti-pathogen
      phagocytosis is to destroy engulfed bacteria or fungi and to stimulate cell-cell
      signaling that mount an efficient immune defense. In contrast, clearance
      phagocytosis of apoptotic cells and cell debris is anti-inflammatory. High
      capacity clearance phagocytosis pathways are available to professional phagocytes
      of the immune system and the retina. Additionally, a low capacity, so-called
      bystander phagocytic pathway is available to most other cell types. Different
      phagocytic pathways are stimulated by particle ligation of distinct surface
      receptors but all forms of phagocytosis require F-actin recruitment beneath
      tethered particles and F-actin re-arrangement promoting engulfment, which are
      controlled by Rho family GTPases. The specificity of Rho GTPase activity during
      the different forms of phagocytosis by mammalian cells is the subject of this
      review. 

PMID- 25941751
TI  - Reciprocal Associations Between Parental Monitoring Knowledge and Impaired
      Driving in Adolescent Novice Drivers.
AB  - OBJECTIVE: Adolescent driving while alcohol/drug impaired (DWI) and parental
      monitoring knowledge may have notable interplay. However, the magnitude and
      direction of causality are unclear. This study examined possible reciprocal
      associations among adolescents between DWI and parental monitoring knowledge.
      METHODS: The data were from waves 1, 2, and 3 (W1, W2, and W3) of the NEXT
      Generation Health Study, with longitudinal assessment of a nationally
      representative sample of 10th graders starting in 2009-2010 (n = 2,525 at W1) and
      analyzed in 2014. Those who had obtained an independent/unsupervised driving
      license were included for the analysis. Autoregressive cross-lagged path analysis
      was used to examine potential reciprocal associations between DWI and parental
      monitoring knowledge of both mothers and fathers, controlling for potential
      confounders. RESULTS: Stability of fathers' and mothers' monitoring knowledge
      across 3 consecutive interview waves was identified. W1 monitoring knowledge of
      both fathers and mothers was prospectively associated with DWI at W2 but not for
      W2 with W3. A significant negative association between adolescent DWI at W2 and
      mothers' monitoring knowledge at W3 was found but not between W1 and W2. None of
      the associations between DWI and fathers' monitoring knowledge from W1 to W2 or
      from W2 to W3 were significant. CONCLUSIONS: Early (10th grade) parental
      monitoring knowledge may predict lower adolescent self-reported DWI in 11th
      grade. More notably, adolescent DWI did not seem to increase parental monitoring
      knowledge. Future interventions are needed to improve parental monitoring
      knowledge and enhance awareness of the DWI risk in their adolescent novice
      drivers.

PMID- 25941752
TI  - Phosphopeptide separation using radially aligned titania nanotubes on titanium
      wire.
AB  - Phosphoproteomic analysis offers a unique view of cellular function and
      regulation in biological systems by providing global measures of a key cellular
      regulator in the form of protein phosphorylation. Understanding the
      phosphorylation changes between normal and diseased cells or tissues offers a
      window into the mechanism of disease and thus potential targets for therapeutic
      intervention. A key step in these studies is the enrichment of phosphorylated
      peptides that are typically separated and analyzed by using liquid chromatography
      mass spectrometry. The mesoporous titania beads/particles (e.g., Titansphere TiO2
      beads from GL Sciences Inc., Japan) that are widely used for phosphopeptide
      enrichment are expensive and offer very limited opportunities for further
      performance improvement. Titiania nanotube arrays have shown promising
      characteristics for phosphopeptide separation. Here we report a proof-of-concept
      study to evaluate the efficacy of nanotubes on Ti-wire for phosphoproteomics
      research. We used titania nanotubes radially grown on titanium wires as well as
      the commercial beads to separate phosphopeptides generated from mouse liver
      complex tissue extracts. Our studies revealed that the nanotubes on metal wire
      provide comparable efficacy for enrichment of phophopeptides and offer an ease of
      use advantage versus mesoporous beads, thus having the potential to become a low
      cost and more practical material/methodology for phosphopeptide enrichment in
      biological studies. 

PMID- 25941753
TI  - Recall of threat material is modulated by self or other referencing in people
      with high or low levels of non-clinical paranoia.
AB  - BACKGROUND AND OBJECTIVES: Biased processing of negatively valenced, and
      particularly threat-related material plays an important role in the development
      of paranoid thinking. This has been demonstrated by superior memory for threat
      related information in patients with persecutory delusions and in non-clinical
      paranoia-prone participants. This study examined how emotional material was
      recalled having been encoded in relation to one self or to another person, in
      people high or low in paranoid ideation. It was predicted that people high in
      paranoia would recall more threat related material about others than people low
      in paranoia owing to being particularly alert to threats from other people.
      METHODS: Participants who reported high (N = 30) or low (N = 30) levels of sub
      clinical paranoid thinking were presented with a series of threat-related and
      positive words and were asked to process them in terms of the self, or in terms
      of a fictional character. RESULTS: As predicted, when words were processed in
      terms of another person, the high paranoia group recalled more threat-related
      words than positive words, but when words had been processed in terms of the
      self, recall of threat-related and positive words did not differ. In contrast,
      there was no interaction between word-valence and referent in the low paranoia
      group. LIMITATIONS: These findings are drawn from an analogue sample. Replication
      in a sample of clinical participants who report persecutory delusions is
      required. CONCLUSIONS: People high in sub-clinical paranoid ideation recalled
      threat preferentially in relation to other people. Such information processing
      biases may help understand the development and maintenance of persecutory
      beliefs.

PMID- 25941754
TI  - Enhanced Production of Nitric Oxide Leads to ATP Collapse in the Retinas of
      Otsuka Long-Evans Tokushima Fatty Rats, a Model of Human Diabetes.
AB  - PURPOSE: We determined nitric oxide (NO) production via inducible NO synthase
      (iNOS) by hyperglycemia using the retina of Otsuka Long-Evans Tokushima Fatty
      rats (OLETF rats), and investigated the relationship between ATP contents and NO
      production in the retinas of OLETF rats. METHODS: Long-Evans Tokushima Otsuka
      rats (LETO rats, normal rats) and OLETF rats (model rat for diabetes mellitus)
      aged 60 weeks of age were used. Plasma glucose (Glu) levels were determined using
      an Accutrend GCT System, and NO levels were measured by the microdialysis method
      as nitrite ([Formula: see text]). Cytochrome c oxidase (CCO) activity was
      measured using a Mitochondrial Isolation Kit and Cytochrome c Oxidase Assay Kit,
      and ATP levels were determined using a Sigma ATP Bioluminescent Assay Kit and a
      luminometer AB-2200. RESULTS: [Formula: see text] levels in the retinas of OLETF
      rats were significantly higher than in LETO rats, and the [Formula: see text]
      levels in the retinas of 60-week-old OLETF rats increased with increasing Glu.
      CCO activity in the retinas of OLETF rats showed no significant difference from
      that in LETO rats; however, ATP levels in the retinas of OLETF rats were
      significantly lower than those in LETO rats. The oral administration of
      aminoguanidine or disulfiram, an iNOS inhibitor, attenuated the decrease in ATP
      levels in the retinas of 60-week-old OELTF rats. CONCLUSION: The present study
      demonstrates that NO production via iNOS in the retinas of 60-week-old OLETF rats
      is caused by hyperglycemia, and that NO causes a decrease in ATP contents in the
      retinas of 60-week-old OELTF rats. It is possible that the low ATP contents
      caused by NO may affect the normal functioning of the retina in OLETF rats.

PMID- 25941755
TI  - Cationic lipophosphoramidates containing a hydroxylated polar headgroup for
      improving gene delivery.
AB  - The structure of the cationic moiety of amphiphiles is a key factor which
      directly influences their transfection efficacy. Accordingly, in the present
      work, we have synthesized three new lipophosphoramide-based amphiphilic compounds
      incorporating a methoxy 5, hydroxyl 6, or dihydroxyl 7 functional group in their
      cationic part. Gene delivery efficacies of these novel vectors were compared to
      our benchmark compound, the arsenolipophosphoramidate KLN47, and to its
      trimethylammonium (TMA) analogue 4. We next studied the characteristics (size,
      zeta potential) of the nanometric assemblies formed (liposomes and lipid/DNA
      complexes), and the DNA binding ability of the cationic liposomes was
      characterized at the physicochemical level. In vitro, all of the cationic lipids
      evaluated were efficient not only to condense plasmids but also to transfect two
      types of human airway epithelial cells. Interestingly, in vivo administration to
      mice (via simple tail vein injection) showed that compound 6 was the most
      efficient in transfecting the lungs when compared to that of the other cationic
      lipids studied, including compound KLN47. All of these results suggest that a
      hydroxyethyldimethylammonium (HE-DMA) polar head could be a valuable alternative
      to a trimethylarsonium (TMAs) polar head and that they also invite further
      evaluation of the in vivo potential of compound 6 using more clinically relevant
      delivery procedures. 

PMID- 25941756
TI  - Complementing Gender Analysis Methods.
AB  - The existing gender analysis frameworks start with a premise that men and women
      are equal and should be treated equally. These frameworks give emphasis on equal
      distribution of resources between men and women and believe that this will bring
      equality which is not always true. Despite equal distribution of resources, women
      tend to suffer and experience discrimination in many areas of their lives such as
      the power to control resources within social relationships, and the need for
      emotional security and reproductive rights within interpersonal relationships.
      These frameworks believe that patriarchy as an institution plays an important
      role in women's oppression, exploitation, and it is a barrier in their
      empowerment and rights. Thus, some think that by ensuring equal distribution of
      resources and empowering women economically, institutions like patriarchy can be
      challenged. These frameworks are based on proposed equality principle which puts
      men and women in competing roles. Thus, the real equality will never be achieved.
      Contrary to the existing gender analysis frameworks, the Complementing Gender
      Analysis framework proposed by the author provides a new approach toward gender
      analysis which not only recognizes the role of economic empowerment and equal
      distribution of resources but suggests to incorporate the concept and role of
      social capital, equity, and doing gender in gender analysis which is based on
      perceived equity principle, putting men and women in complementing roles that may
      lead to equality. In this article the author reviews the mainstream gender
      theories in development from the viewpoint of the complementary roles of gender.
      This alternative view is argued based on existing literature and an anecdote of
      observations made by the author. While criticizing the equality theory, the
      author offers equity theory in resolving the gender conflict by using the concept
      of social and psychological capital. 

PMID- 25941757
TI  - Evaluation of surfactant flushing for remediating EDC-tar contamination.
AB  - Ethylene dichloride tar (EDC-tar) is a dense non-aqueous phase liquid (DNAPL)
      waste originated from the process of vinyl chloride production, with major
      constituents including chlorinated aliphatic and aromatic hydrocarbons. This
      study investigated the feasibility of Surfactant Enhanced Aquifer Remediation
      (SEAR) for treating EDC-tar contaminated aquifers. Initial experiments explored
      the potential to enhance the apparent solubility of EDC-tar using single or mixed
      surfactants. The results showed that an aqueous solution mixed anionic and non
      ionic surfactants (i.e., SDS/Tween 80) exhibited higher EDC-tar apparent
      solubility and lower surface tension than other surfactant systems tested.
      Additionally, alkaline pH aids in increasing the EDC-tar apparent solubility. In
      column flushing experiments, it was seen that the alkaline mixed SDS/Tween 80
      solution showed better removal of pure EDC-tar from silica sand porous media.
      Furthermore, separation of EDC-tar in the surfactant solution was conducted
      employing a salting-out effect. Significant separation of DNAPL was observed when
      13 wt.% or more NaCl was added to the solution. Overall, this study evaluates the
      feasibility of using SEAR for remediating EDC-tar contaminated subsurface soil
      and groundwater.

PMID- 25941758
TI  - Biomethanation from enzymatically hydrolyzed brewer's spent grain: Impact of
      rapid increase in loadings.
AB  - Enzymatically hydrolyzed brewer's spent grain (BSG) was digested in two expanded
      granular sludge beds (EGSBs, named BSG1 and BSG2, respectively). Both reactors
      were operated with the same organic loading rate (OLR) from 1 to 10kgCODm(-3)d(
      1) during the first 45days. Hereafter a rapid OLR increase was applied to BSG2
      from 10 to 16kgCODm(-3)d(-1) within three weeks, while the OLR of BSG1 was
      increased by less than 2kgCODm(-3)d(-1) in the same period. Results showed that a
      30% decrease in COD removal and 70% decrease in methane yield appeared in BSG2
      after the rapid OLR increase, and volatile fatty acid (VFA) accumulated more than
      thirty times compared to BSG1. The biomass structure deteriorated and 15% of the
      biomass was lost from the BSG2 reactor. 454-PyroTag and qPCR analysis revealed a
      rapid growth of acidifiers (i.e., Bacteroides) and a unique microbial community
      in BSG2 following the rapid increase in OLR. 

PMID- 25941759
TI  - Performance variation according to anode-embedded orientation in a sediment
      microbial fuel cell employing a chessboard-like hundred-piece anode.
AB  - The effect of two different anode-embedding orientations, lengthwise- and
      widthwise-embedded anodes was explored, on the performance of sediment microbial
      fuel cells (SMFCs) using a chessboard anode. The maximum current densities and
      power densities in SMFCs having lengthwise-embedded anodes (SLA1-SLA10) varied
      from 38.2mA/m(2) to 121mA/m(2) and from 5.5mW/m(2) to 20mW/m(2). In comparison,
      the maximum current densities and maximum power densities in SMFCs having anodes
      widthwise-embedded between 0cm to 8cm (SWA2-SWA5) increased from 82mA/m(2) to
      140mA/m(2) and from 14.7mW/m(2) to 31.1mW/m(2) as the anode depth became deeper.
      Although there was a difference in the performance among SWA5-SWA10, it was
      considered negligible. Hence, it is concluded that it is important to embed
      anodes widthwise at the specific anode depths, in order to improve of SMFC
      performance. Chessboard anode used in this work could be a good option for the
      determination of optimal anode depths. 

PMID- 25941762
TI  - ERRATUM: Blood ammonia and glutamine as predictors of hyperammonemic crises in
      patients with urea cycle disorder.

PMID- 25941763
TI  - Enantioselective rhodium-catalyzed allylic substitution with a nitrile anion:
      construction of acyclic quaternary carbon stereogenic centers.
AB  - A direct and highly enantioselective rhodium-catalyzed allylic alkylation of
      allyl benzoate with alpha-substituted benzyl nitrile pronucleophiles is
      described. This simple protocol provides a new approach toward the synthesis of
      acyclic quaternary carbon stereogenic centers and provides the first example of
      the direct asymmetric alkylation of a nitrile anion. The synthetic utility of the
      nitrile products is amply demonstrated through conversion to various functional
      groups and the synthesis of a bioactive aryl piperazine in an expeditious four
      step sequence. 

PMID- 25941764
TI  - Genetic approaches for improvement of the crop potassium acquisition and
      utilization efficiency.
AB  - Potassium (K) is one of the essential macronutrients for higher plants, not only
      important for plant growth and development, but also crucial for crop yield and
      quality. The deficiency in K in large areas of arable land worldwide has become a
      limitation for sustainable development of agriculture, and threatens the world
      food security. Along with the increased limitation of K fertilizer supply, the
      genetic improvement of K utilization efficiency (KUE) of crop plants may become a
      feasible way to solve the problem. K nutrition depends on an underlying
      relationship with metabolic regulation which together influence crop yield,
      quality and responses to environmental stress. Manipulation of root architecture
      together with K transport and distribution within the plant offer great potential
      to improve KUE. 

PMID- 25941765
TI  - Coenzyme Q10 supplementation downregulates the increase of monocytes expressing
      toll-like receptor 4 in response to 6-day intensive training in kendo athletes.
AB  - This study examined changes in toll-like receptor 4 (TLR-4)-expressing monocytes
      and lymphocyte subpopulations in response to continuous intensive exercise
      training in athletes, as well as the effect of coenzyme Q10 (CoQ10)
      supplementation on these changes. Eighteen male elite kendo athletes in Japan
      were randomly assigned to a CoQ10-supplementation group (n = 9) or a placebo
      supplementation group (n = 9) using a double-blind method. Subjects in the CoQ10
      group took 300 mg CoQ10 per day for 20 days. Subjects in the placebo group took
      the same dosage of placebo. All subjects practiced kendo 5.5 h per day for 6
      consecutive days during the study period. Blood samples were collected 2 weeks
      before training, on the first day (day 1), third day (day 3), and fifth day of
      training (day 5), and 1 week after the training period (post-training) to
      ascertain TLR-4(+)/CD14(+) monocyte and lymphocyte subpopulations (CD3(+),
      CD4(+), CD8(+), CD28(+)/CD4(+), CD28(+)/CD8(+), and CD56(+)/CD3(-) cells) using
      flow cytometry analysis. The group * time interaction for TLR-4(+)/CD14(+) cells
      did not reach significance (p = 0.08). Within the CoQ10 group, the absolute
      number of TLR-4(+)/CD14(+) cells was significantly higher only at day 5. The
      placebo group showed a significant increase in the absolute number of TLR
      4(+)/CD14(+) cells at day 3, day 5, and post-training (p < 0.05). There was no
      significant group * time interaction for any lymphocyte subpopulation. CD3(+),
      CD8(+), and CD56(+)/CD3(-) cells were significantly reduced at day 3 in both
      groups (p < 0.05). In conclusion, CoQ10 supplementation might downregulate the
      increase of TLR-4-expressing monocytes in response to continuous strenuous
      exercise training in kendo athletes. 

PMID- 25941766
TI  - Membrane-Pore Forming Characteristics of the Bordetella pertussis CyaA-Hemolysin
      Domain.
AB  - Previously, the 126-kDa Bordetella pertussis CyaA pore-forming/hemolysin (CyaA
      Hly) domain was shown to retain its hemolytic activity causing lysis of
      susceptible erythrocytes. Here, we have succeeded in producing, at large quantity
      and high purity, the His-tagged CyaA-Hly domain over-expressed in Escherichia
      coli as a soluble hemolytically-active form. Quantitative assays of hemolysis
      against sheep erythrocytes revealed that the purified CyaA-Hly domain could
      function cooperatively by forming an oligomeric pore in the target cell membrane
      with a Hill coefficient of ~3. When the CyaA-Hly toxin was incorporated into
      planar lipid bilayers (PLBs) under symmetrical conditions at 1.0 M KCl, 10 mM
      HEPES buffer (pH 7.4), it produced a clearly resolved single channel with a
      maximum conductance of ~35 pS. PLB results also revealed that the CyaA-Hly
      induced channel was unidirectional and opened more frequently at higher negative
      membrane potentials. Altogether, our results first provide more insights into
      pore-forming characteristics of the CyaA-Hly domain as being the major pore
      forming determinant of which the ability to induce such ion channels in receptor
      free membranes could account for its cooperative hemolytic action on the target
      erythrocytes. 

PMID- 25941768
TI  - Extracts of Renealmia alpinia (Rottb.) MAAS Protect against Lethality and
      Systemic Hemorrhage Induced by Bothrops asper Venom: Insights from a Model with
      Extract Administration before Venom Injection.
AB  - Renealmia alpinia (Rottb.) MAAS, obtained by micropropagation (in vitro) and wild
      forms have previously been shown to inhibit some toxic activities of Bothrops
      asper snake venom if preincubated before injection. In this study, assays were
      performed in a murine model in which extracts were administered for three days
      before venom injection. R. alpinia extracts inhibited lethal activity of B. asper
      venom injected by intraperitoneal route. Median Effective Dose (ED50) values were
      36.6 +/- 3.2 mg/kg and 31.7 +/- 5.4 mg/kg (p > 0.05) for R. alpinia wild and in
      vitro extracts, respectively. At a dose of 75 mg/kg, both extracts totally
      inhibited the lethal activity of the venom. Moreover, this dose prolonged
      survival time of mice receiving a lethal dose of venom by the intravenous route.
      At 75 mg/kg, both extracts of R. alpinia reduced the extent of venom-induced
      pulmonary hemorrhage by 48.0% (in vitro extract) and 34.7% (wild extract), in
      agreement with histological observations of lung tissue. R. alpinia extracts also
      inhibited hemorrhage in heart and kidneys, as evidenced by a decrease in mg of
      hemoglobin/g of organ. These results suggest the possibility of using R. alpinia
      as a prophylactic agent in snakebite, a hypothesis that needs to be further
      explored. 

PMID- 25941769
TI  - Cost-effectiveness of selective internal radiation therapy using yttrium-90 resin
      microspheres in treating patients with inoperable colorectal liver metastases in
      the UK.
AB  - OBJECTIVE: Selective internal radiation therapy (SIRT) using SIR-Spheres((r))
      (90)Y-labeled resin microspheres has been shown to be a well-tolerated, effective
      treatment in patients with inoperable liver-dominant chemotherapy-refractory
      metastatic colorectal cancer (mCRC). This study estimated the cost-effectiveness
      of (90)Y-resin microspheres compared to best supportive care (BSC) from a UK
      perspective. METHODS: Survival data from a comparative retrospective cohort study
      was analyzed and used in a state-transition cost-effectiveness model, using
      quality-adjusted life years (QALYs) gained as the measure of effectiveness. The
      model incorporated costs for the SIRT procedure, monitoring, further treatment,
      adverse events, and death. Utility values, reflecting patient quality-of-life,
      were taken from a published source. RESULTS: SIRT using (90)Y-resin microspheres
      compared to BSC improved overall survival by a mean of 1.12 life years and
      resulted in a cost per QALY gained of L28,216. In sensitivity analysis, this
      varied between L25,015-L28,817. CONCLUSION: In an area of large unmet need,
      treatment with (90)Y-resin microspheres offers a clinically effective and cost
      effective treatment option.

PMID- 25941767
TI  - Bioactive components in fish venoms.
AB  - Animal venoms are widely recognized excellent resources for the discovery of
      novel drug leads and physiological tools. Most are comprised of a large number of
      components, of which the enzymes, small peptides, and proteins are studied for
      their important bioactivities. However, in spite of there being over 2000
      venomous fish species, piscine venoms have been relatively underrepresented in
      the literature thus far. Most studies have explored whole or partially fractioned
      venom, revealing broad pharmacology, which includes cardiovascular,
      neuromuscular, cytotoxic, inflammatory, and nociceptive activities. Several large
      proteinaceous toxins, such as stonustoxin, verrucotoxin, and Sp-CTx, have been
      isolated from scorpaenoid fish. These form pores in cell membranes, resulting in
      cell death and creating a cascade of reactions that result in many, but not all,
      of the physiological symptoms observed from envenomation. Additionally,
      Natterins, a novel family of toxins possessing kininogenase activity have been
      found in toadfish venom. A variety of smaller protein toxins, as well as a small
      number of peptides, enzymes, and non-proteinaceous molecules have also been
      isolated from a range of fish venoms, but most remain poorly characterized. Many
      other bioactive fish venom components remain to be discovered and investigated.
      These represent an untapped treasure of potentially useful molecules. 

PMID- 25941770
TI  - Soft contact transplanted nanocrystal quantum dots for light-emitting diodes:
      effect of surface energy on device performance.
AB  - To realize the full-color displays using colloidal nanocrystal quantum dot (QD)
      based light emitting diodes (QLEDs), the emissive QD layer should be patterned to
      red (R), green (G), and blue (B) subpixels on a micrometer scale by the solution
      process. Here, we introduced a soft contact QD-transplanting technique onto the
      vacuum-deposited small molecules without pressure to pattern the QD layer without
      any damage to the prior organic layers. We examined the patternability of QDs by
      studying the surface properties of various organic layers systematically. As a
      result, we found that the vacuum-deposited 4,4',4"-tri(N
      carbazolyl)triphenylamine (TCTA) layer is suitable for QD-transplanting. A
      uniform and homogeneous QD patterns down to 2 MUm could be formed for all the RGB
      QDs (CdSe/CdS/ZnS, CdSe@ZnS, and Cd1-xZnxS@ZnS, respectively) with this method.
      Finally, we demonstrated the R, G, and B QLEDs by transplanting each QD onto the
      soft TCTA layer, exhibiting higher brightness (2497, 14 102, and 265 cd m(-2),
      respectively) and efficiency (1.83, 8.07, and 0.19 cd A(-1), respectively) than
      those of the previous QLEDs fabricated by other patterning methods. Because this
      pressure-free technique is essential for patterning and stacking the QDs onto the
      soft organic layer, we believe that both fundamental study and the engineering
      approach presented here are meaningful for the realization of the colloidal QD
      based full-color displays and other optoelectronic devices. 

PMID- 25941771
TI  - Legislating for Filial Piety: An Indirect Approach to Promoting Family Support
      and Responsibility for Older People in Korea.
AB  - Although every culture follows its own indigenous elder care practices, Korea has
      retained a unique way of supporting elder parents, specifically, and older people
      in general. When the care of older people in Korea became significantly
      challenging, it was determined to launch a controversial law to promote the
      tradition of filial piety. The main content of the law consists of requiring the
      government to take action to encourage filial piety and to support those adult
      children who care for their parents. Although this legislation has the potential
      to promote the practice of filial piety, the nature of the law is largely
      rhetorical and symbolic rather than practical, and as a result, its workability
      and efficiency are limited. 

PMID- 25941772
TI  - ROMK (Kir1.1) pharmacology comes of age.

PMID- 25941773
TI  - Effect of Hyaluronic Acid-carboxymethylcellulose Adhesion Barrier on Wound
      Healing: An Experimental Study.
AB  - The aim of this study was to investigate the effects of hyaluronic acid
      carboxymethylcellulose (HA-CMC) membrane on the healing process of wounds in
      rats. One hundred animals were assigned randomly into two equal groups. Midline
      laparotomies were performed. In group 1, a 5-cm x 3-cm piece of HA-CMC membrane
      was placed under the laparotomy incision. The same procedure was performed in
      group 2, but without the HA-CMC membrane. Ten animals from each group were
      euthanized on postoperative days (POD) 4, 7, 14, 21, and 35 after wounding.
      Breaking strength, histologic examination, and tissue hydroxyproline levels were
      analyzed. The tensiometric test showed that there was no significant difference
      in the breaking strengths between the two groups (P > 0.05). Statistical
      difference was found to be significant on POD 4, 14, 21, and 35 when the groups
      were compared with regard to average hydroxyproline levels (P < 0.05).
      Significant differences were found in the results of histologic examination of
      the tissue specimens between the two groups in terms of acute inflammation on POD
      14, chronic inflammation, and granulation tissue fibroblast maturation on POD 35,
      collagen deposition on POD 21, and neovascularization on POD 7, 14, 21, and 35 (P
      < 0.05). The results show that the HA-CMC membrane did not negatively affect the
      mechanical strength and healing process of the laparotomy incisions. 

PMID- 25941774
TI  - A Comparison of Three Silver-containing Dressings in the Treatment of Infected,
      Chronic Wounds .
AB  - Objective. To compare 3 types of silver dressing in the typical clinical
      conditions of a community health center, regarding the time to achieve resolution
      of clinical signs of local infection, and wound healing progress over 8 weeks.
      METHODS: A prospective, comparative study involving 75 patients with infected
      chronic wounds who were divided into 3 treatment groups: ActicoatTM (group 1);
      Comfeel(r) Ag hydrocolloid/Biatain(r) Ag polyurethane foam (group 2); and
      Aquacel(r) Ag (group 3). RESULTS: The groups were comparable at baseline.
      Clinical signs of infection were resolved faster in group 1 than in the other two
      groups (P <0.05, median: group 1 = 2 weeks; group 2 = 4 weeks; group 3 = 4 weeks.
      Group 1 required fewer treatments to eliminate the clinical signs of infection
      (median: group 1 = 6 treatments; group 2 = 12 treatments; group 3 = 12
      treatments). Patients in group 1 healed faster than patients in the other 2
      groups (P < 0.05). CONCLUSION: The treatment in group 1 was more effective than
      that of groups 2 and 3 in the treatment of infected, chronic wounds. Clinical
      signs of infection were resolved faster (P < 0.05) and wounds healed more quickly
      (P < 0.05) in group 1 than in the other 2 groups.    .

PMID- 25941775
TI  -  Patient satisfaction with a tissue adhesive in preauricular fistulectomy    .
AB  - Objective. To evaluate the usefulness of Dermabond(r) (octyl-2-cyanoacrylate)
      tissue adhesive, and to provide advice on its use for patients undergoing
      preauricular fistulectomy. STUDY DESIGN: A retrospective, IRB-approved, case
      control study. METHODS: This study reviewed the medical records of patients who
      underwent preauricular fistulectomy by one otologist at a single institution.
      Patient satisfaction was assessed by a questionnaire and the cosmetic result was
      assessed using the Hollander Wound Evaluation Scale (HWES). RESULTS: There were 2
      cases of wound dehiscence; a stitch abscess was noted in 2 patients.
      Aesthetically, scar appearance was considered very good. Among 33 patients who
      expressed an opinion postoperatively regarding the use of the tissue adhesive for
      skin closure, the degree of satisfaction was considerably high because patients
      were able to wash their face and bathe/shower (28 patients) soon after the
      procedure, followed by the lack of any dressing or wound care (21 patients), and
      the lack of skin sutures (19 patients). CONCLUSION: The tissue adhesive offered
      equivalent wound closure as traditional suture for preauricular fistulectomy.
      Tissue adhesive is a safe method for closing wounds in preauricular fistulectomy
      and has many advantages, especially in young children and young women.

PMID- 25941776
TI  -    Quantitation of bacteria in clean, nonhealing, chronic wounds.
AB  - Quantitative swabs were obtained from 30 clean, chronic wounds on 30 different
      patients during one visit. The number of organisms and the predominant organism
      were determined. All samples were processed under both aerobic and anaerobic
      conditions. Nineteen (63%) of the 30 clean wounds had bacterial levels that were
      >= 105 cfu/cm2. There was no correlation between >= 105 cfu/cm2 and delayed wound
      healing. The most frequently isolated predominant organism was Staphylococcus
      aureus. In these clean, chronic wounds, an obligate anaerobic organism was
      identified as predominant or co-predominant in only 2 (6.7%) of 30 wounds. 

PMID- 25941777
TI  - Alcohol-soluble bis(tpy)thiophenes: new building units for constitutional dynamic
      conjugated polyelectrolytes.
AB  - New building units (unimers) for metallo-supramolecular polymers 2,5
      bis(2,2':6',2''-terpyridine-4'-yl)thiophene, M, and 5,5'-bis(2,2':6',2''
      terpyridine-4'-yl)(2,2'-bithiophene), B, with ionic groups attached to thiophene
      rings are prepared by the modification of corresponding bromo-precursors and
      assembled with Zn(2+) and Fe(2+) ions into alcohol-soluble conjugated
      constitutional-dynamic polyelectrolytes (polyelectrolyte dynamers). Ionization of
      side groups only slightly affects the absorption spectra of unimers as well as
      dynamers but dramatically changes their solubility. Cyclic conformations of
      unimer molecules resulting from intramolecular interactions between tpy end
      groups and cationic or polar (-CH2Br) side groups are proposed to explain the
      spectral conformity of the M- and B-type unimers and their dynamers and also
      inhibition of the ionization reaction with tpy end-groups. The absorption spectra
      and excitation profiles of Raman spectra show that mainly the red arm of the
      metal-to-ligand charge transfer band of Fe-dynamers is significantly contributed
      with transitions involving thiophene rings. The constitutional dynamics of Zn
      dynamers is fast while that of Fe-dynamers is so slow that it allows effective
      separation of the dynamer to fractions in SEC columns. Electronic spectra and
      viscosity measurements proved that excess of Fe(2+) ions results in shortening of
      the dynamer chains and their end-capping by these ions.

PMID- 25941778
TI  - Intracellular surface-enhanced Raman scattering probes based on TAT peptide
      conjugated Au nanostars for distinguishing the differentiation of lung resident
      mesenchymal stem cells.
AB  - Lung resident mesenchymal stem cells (LR-MSCs) are important regulators of
      pathophysiological processes including tissue repair and fibrosis, inflammation,
      angiogenesis and tumor formation. Therefore, increasing attention has focused on
      the functional differentiation of LR-MSCs. However, the distinction between the
      undifferentiated and differentiated LR-MSCs, which are closely related and
      morphologically similar, is difficult to achieve by conventional methods. In this
      study, by employing the TAT Peptide-conjugated Au nanostars (AuNSs) as an
      intracellular probe, we developed a method for the identification of LR-MSC
      differentiation by surface-enhanced Raman scattering (SERS) spectroscopy. SERS
      spectra were analyzed using principal component analysis (PCA) that allowed
      unambiguous distinction of subtypes and monitoring of component changes during
      cellular differentiation. Furthermore, to ascertain whether co-culture with
      alveolar epithelial type II (ATII) cells and incubation with transform growth
      factor (TGF)-beta were involved in regulating the differentiation of LR-MSCs, we
      investigated the protein expression levels of epithelial markers and fibroblastic
      markers on LR-MSCs. Our results demonstrated that co-culture with ATII cells or
      incubation with TGF-beta could induce the differentiation of LR-MSCs as confirmed
      by SERS analysis, a method that is capable of noninvasive characterization of and
      distinction between subtypes of LR-MSCs during differentiation. We have provided
      a new tool that may facilitate stem cell research. 

PMID- 25941779
TI  - A bio-inspired, microchanneled hydrogel with controlled spacing of cell adhesion
      ligands regulates 3D spatial organization of cells and tissue.
AB  - Bioactive hydrogels have been extensively studied as a platform for 3D cell
      culture and tissue regeneration. One of the key desired design parameters is the
      ability to control spatial organization of biomolecules and cells and subsequent
      tissue in a 3D matrix. To this end, this study presents a simple but advanced
      method to spatially organize microchanneled, cell adherent gel blocks and non
      adherent ones in a single construct. This hydrogel system was prepared by first
      fabricating a bimodal hydrogel in which the microscale, alginate gel blocks
      modified with cell adhesion peptides containing Arg-Gly-Asp sequence (RGD
      peptides), and those free of RGD peptides, were alternatingly presented. Then,
      anisotropically aligned microchannels were introduced by uniaxial freeze-drying
      of the bimodal hydrogel. The resulting gel system could drive bone marrow stromal
      cells to adhere to and differentiate into neuron and glial cells exclusively in
      microchannels of the alginate gel blocks modified with RGD peptides. Separately,
      the bimodal gel loaded with microparticles releasing vascular endothelial growth
      factor stimulated vascular growth solely into microchannels of the RGD-alginate
      gel blocks in vivo. These results were not attained by the bimodal hydrogel
      fabricated to present randomly oriented micropores. Overall, the bimodal gel
      system could regulate spatial organization of nerve-like tissue or blood vessels
      at sub-micrometer length scale. We believe that the hydrogel assembly
      demonstrated in this study will be highly useful in developing a better
      understanding of diverse cellular behaviors in 3D tissue and further improve
      quality of a wide array of engineered tissues.

PMID- 25941781
TI  - Micropatterned bioimplant with guided neuronal cells to promote tissue
      reconstruction and improve functional recovery after primary motor cortex insult.
AB  - With the ever increasing incidence of brain injury, developing new tissue
      engineering strategies to promote neural tissue regeneration is an enormous
      challenge. The goal of this study was to design and evaluate an implantable
      scaffold capable of directing neurite and axonal growth for neuronal brain tissue
      regeneration. We have previously shown in cell culture conditions that engineered
      micropatterned PDMS surface with straight microchannels allow directed neurite
      growth without perturbing cell differentiation and neurite outgrowth. In this
      study, the micropatterned PDMS device pre-seeded with hNT2 neuronal cells were
      implanted in rat model of primary motor cortex lesion which induced a strong
      motor deficit. Functional recovery was assessed by the forelimb grip strength
      test during 3 months post implantation. Results show a more rapid and efficient
      motor recovery with the hNT2 neuroimplants associated with an increase of
      neuronal tissue reconstruction and cell survival. This improvement is also
      hastened when compared to a direct cell graft of ten times more cells.
      Histological analyses showed that the implant remained structurally intact and we
      did not see any evidence of inflammatory reaction. In conclusion, PDMS
      bioimplants with guided neuronal cells seem to be a promising approach for
      supporting neural tissue reconstruction after central brain injury. 

PMID- 25941780
TI  - Programmed packaging of mesoporous silica nanocarriers for matrix metalloprotease
      2-triggered tumor targeting and release.
AB  - The development of multifunctional nanocarrier with each unit functioning at the
      correct time and location is a challenge for clinical applications. With this in
      mind, a type of intelligent mesoporous silica nanocarrier (PGFMSN) is proposed
      for matrix metalloprotease 2 (MMP 2)-triggered tumor targeting and release by
      integrating programmed packing and MMP 2-degradable gelatin. Mesoporous silica
      nanoparticles (MSN) are first functionalized with folic acid (FA) as a target
      ligand to improve cell uptake. Then gelatin is introduced onto FA-MSN via
      temperature-induced gelation, where gelatin layer blocks drugs inside the
      mesopores and protects the targeting ligand. To prolong blood-circulation
      lifetime, PEG is further decorated to obtain PGFMSN. All units are
      programmatically incorporated in a simple way and coordinated in an optimal
      fashion. Cells, multicellular spheroids and in vivo results demonstrate that
      PGFMSN is shielded against nonspecific uptake. After circulating to tumor tissue,
      the up-regulated MMP-2 hydrolyzes gelatin layer to deshield PEG and switch on the
      function of FA, which facilitate the selective uptake by tumor cells through
      folate-receptor-mediated endocytosis. Meanwhile, the packaged drug is released
      due to the shedding of gelatin layer. It is shown that doxorubicin (DOX)-loaded
      exhibits superior tumor targeting, drug internalization, cytotoxicity, and
      antitumor efficacy over free DOX, non-PEGylated and non-targeted nanoparticles,
      which provides potential applications for targeted cancer therapy.

PMID- 25941782
TI  - Tissue-engineered acellular small diameter long-bypass grafts with neointima
      inducing activity.
AB  - Researchers have attempted to develop efficient antithrombogenic surfaces, and
      yet small-caliber artificial vascular grafts are still unavailable. Here, we
      demonstrate the excellent patency of tissue-engineered small-caliber long-bypass
      grafts measuring 20-30 cm in length and having a 2-mm inner diameter. The inner
      surface of an acellular ostrich carotid artery was modified with a novel
      heterobifunctional peptide composed of a collagen-binding region and the integrin
      alpha4beta1 ligand, REDV. Six grafts were transplanted in the femoral-femoral
      artery crossover bypass method. Animals were observed for 20 days and received no
      anticoagulant medication. No thrombogenesis was observed on the luminal surface
      and five cases were patent. In contrast, all unmodified grafts became occluded,
      and severe thrombosis was observed. The vascular grafts reported here are the
      first successful demonstrations of short-term patency at clinically applicable
      sizes.

PMID- 25941783
TI  - Superparamagnetic MRI probes for in vivo tracking of dendritic cell migration
      with a clinical 3 T scanner.
AB  - Dendritic cell (DC) based vaccines have shown promising results in the
      immunotherapy of cancers and other diseases. How to track the in vivo fate of DC
      vaccines will provide important insights to the final therapeutic results. In
      this study, we chose magnetic resonance imaging (MRI) to track murine DCs
      migration to the draining lymph node under a clinical 3 T scanner. Different from
      labeling immature DCs usually reported in literature, this study instead labeled
      matured DC with superparamagnetic iron oxide (SPIO) nanoparticle based imaging
      probes. The labeling process did not show negative impacts on cell viability,
      morphology, and surface biomarker expression. To overcome the imaging challenges
      brought by the limitations of the scanner, the size of lymph node, and the number
      of labeled cell, we optimized MRI pulse sequences. As a result, the signal
      reduction, caused either by gelatin phantoms containing as low as 12 SPIO-laden
      cells in each voxel or by the homing SPIO-laden DCs within the draining nodes
      after footpad injection of only 1 * 10(5) cells, can be clearly depicted under a
      3 T MR scanner. Overall, the MRI labeling probes offer a low-toxic and high
      efficient MR imaging platform for the assessment of DC-based immunotherapies.

PMID- 25941784
TI  - A fast and selective two-photon phosphorescent probe for the imaging of nitric
      oxide in mitochondria.
AB  - Nitric oxide (NO) is a vitally important cellular messenger molecule related to
      numerous physiological events and diseases. It is more than 10 years now that
      mitochondria are suspected to be sources of nitric oxide. Hence, mitochondrial NO
      tracking probes play an indispensable role in NO behavior analysis. However, a
      majority of previously reported NO probes can only be employed under one-photon
      microscopy, often with several drawbacks during application. In the present
      study, an iridium(III) complex containing 1,10-phenanthroline-5,6-diamine (Ir
      Mito-NO) was synthesized and determined to possess high specificity to NO in
      mitochondria, low cytotoxicity, and rapid and specific "off-on" two-photon
      phosphorescence. Thus, this complex was developed to image mitochondrial NO
      levels in living cells, 3D multicellular spheroids and zebrafish. 

PMID- 25941785
TI  - Gd-loaded-RBCs for the assessment of tumor vascular volume by contrast-enhanced
      MRI.
AB  - The assessment of the fractional vascular volume (vV) in the tumor area is of
      great interest in the characterization of tumor and it can be useful to monitor
      the outcome of anti-angiogenetic therapies. The high spatial and temporal
      resolution of Magnetic Resonance Imaging makes it the election imaging modality
      to monitor in vivo the vascular volume changes. Commonly used MRI methods to
      obtain this information rely on the administration of contrast agents that modify
      the bulk water relaxation times but, unfortunately, they can provide only an
      estimate of vV since they are not fully retained in the vascular space. Herein,
      Gd-loaded Red Blood Cells (Gd-RBCs) are proposed as a contrast agent able to
      provide quantitative information on tumor vascularization. Being Gd-RBCs fully
      retained in the vascular space, the proposed method does not suffer for the
      limitations associated to the use of extracellular Gd-agents that quickly
      extravasate in the leaky tumor vasculature. Furthermore, the long half-life and
      biocompatibility of Gd-RBCs allows repeating the measurement many times upon
      their administration; this ensures the possibility to in vivo evaluate the change
      of vascular volume during tumor growth. For these reasons, Gd-RBCs may represent
      a highly biocompatible imaging reporter of vasculature, able to quantitatively
      assess changes in the vascular volume in the ROI.

PMID- 25941786
TI  - In situ hybridization of carbon nanotubes with bacterial cellulose for three
      dimensional hybrid bioscaffolds.
AB  - Carbon nanotubes (CNTs) have shown great potential in biomedical fields. However,
      in vivo applications of CNTs for regenerative medicine have been hampered by
      difficulties associated with the fabrication of three-dimensional (3D) scaffolds
      of CNTs due to CNTs' nano-scale nature. In this study, we devised a new method
      for biosynthesis of CNT-based 3D scaffold by in situ hybridizing CNTs with
      bacterial cellulose (BC), which has a structure ideal for tissue-engineering
      scaffolds. This was achieved simply by culturing Gluconacetobacter xylinus, BC
      synthesizing bacteria, in medium containing CNTs. However, pristine CNTs
      aggregated in medium, which hampers homogeneous hybridization of CNTs with BC
      scaffolds, and the binding energy between hydrophobic pristine CNTs and
      hydrophilic BC was too small for the hybridization to occur. To overcome these
      problems, an amphiphilic comb-like polymer (APCLP) was adsorbed on CNTs. Unlike
      CNT-coated BC scaffolds (CNT-BC-Imm) formed by immersing 3D BC scaffolds in CNT
      solution, the APCLP-adsorbed CNT-BC hybrid scaffold (CNT-BC-Syn) showed
      homogeneously distributed CNTs throughout the 3D microporous structure of BC.
      Importantly, in contrast to CNT-BC-Imm scaffolds, CNT-BC-Syn scaffolds showed
      excellent osteoconductivity and osteoinductivity that led to high bone
      regeneration efficacy. This strategy may open a new avenue for development of 3D
      biofunctional scaffolds for regenerative medicine. 

PMID- 25941788
TI  - Prostate cancer: Can image-guided biopsy findings evaluate risk of ECE?

PMID- 25941787
TI  - Influence of molecular weight upon mannosylated bio-synthetic hybrids for
      targeted antigen presenting cell gene delivery.
AB  - Given the rise of antibiotic resistant microbes, genetic vaccination is a
      promising prophylactic strategy that enables rapid design and manufacture.
      Facilitating this process is the choice of vector, which is often situationally
      specific and limited in engineering capacity. Furthermore, these shortcomings are
      usually tied to an incomplete understanding of the structure-function
      relationships driving vector-mediated gene delivery. Building upon our initial
      report of a hybrid bacterial-biomaterial gene delivery vector, a comprehensive
      structure-function assessment was completed using a class of mannosylated
      poly(beta-amino esters). Through a top-down screening methodology, an ideal
      polymer was selected on the basis of gene delivery efficacy and then used for the
      synthesis of a stratified molecular weight polymer library. By eliminating
      contributions of polymer chemical background, we were able to complete an in
      depth assessment of gene delivery as a function of (1) polymer molecular weight,
      (2) relative mannose content, (3) polymer-membrane biophysical properties, (4)
      APC uptake specificity, and (5) serum inhibition. In summary, the flexibility and
      potential of the hybrid design featured in this work highlights the ability to
      systematically probe vector-associated properties for the development of
      translational gene delivery candidates. 

PMID- 25941789
TI  - Infectious disease: New HIV-1 prodrug shows promise in phase III trials.

PMID- 25941790
TI  - Prostate cancer: Can imaging accurately diagnose lymph node involvement?

PMID- 25941791
TI  - Definitive repair of a stab wound to the right ventricle with skin staples in
      emergency.
AB  - Penetrating cardiac injuries represent a challenge to surgeons. Several
      surgical techniques for repair of these injuries have been described. The authors
      report on the use of skin staples for a right ventricular stab wound in a patient
      in extremis. 

PMID- 25941792
TI  - A Retrospective Review of the Outcomes of Vacuum-assisted Closure Therapy in a
      Vascular Surgery Unit     .
AB  - Wound problems are common in vascular surgery. They pose a therapeutic dilemma
      due to multiple etiologies. The use of vacuum-assisted closure (V.A.C.(r), KCI,
      San Antonio, Tex), or negative pressure wound therapy (NPWT) has increased
      despite conflicting reports regarding its effectiveness. A retrospective review
      of 74 patients was conducted from 2002 to 2006 to assess the success of NPWT
      usage. Thirty-four (45.9%) patients were women and 40 (54.1%) men with median age
      of 65.5. There were 77 wounds in total: 25 foot, 13 toe and groin, 9 leg and
      thigh, 7 trunk, and 1 neck. Twenty-nine (37.7%) of these wounds were a result of
      surgical incision breakdown. Majority (n = 42, 54.5%) were infected secondary
      wounds. Six (7.8%) were infected wounds that broke down after initial closure.
      Overall surface area was 18.7 cm2: toe (15 cm2), foot (20 cm2), leg (32 cm2),
      thigh (57.5 cm2), groin (20 cm2), trunk (15 cm2), and neck (1.5 cm2). The median
      duration of NPWT was 11 days: toe (7.4), foot (12.2), leg (11.4), thigh (19),
      groin (15.6), trunk (18.4), and neck (1). The median length of stay in hospital
      was 36 days: toe (29.9), foot (44.5), leg (39.4), thigh (59.8), groin (35.2),
      trunk (45), and neck (35). RESULTS: The median healing time was 86 days. Overall
      healing was 75.4% (n >= 46). The predictors of poor healing were distal location,
      higher left dorsalis pedis value, stroke, peripheral vascular disease,
      retinopathy, dietary input, and supplementation. Weight gain, high dependency
      area (HDA) admission, combination hypoglycemic therapy, and steroid use were
      associated with faster healing. CONCLUSION: The success of vacuum-assisted
      closure is best above the ankle where the blood supply is usually adequate in
      vascular patients.    .

PMID- 25941793
TI  -     Calendula officinalis and Wound Healing: A Systematic Review.
AB  - The treatment options available for the management of most types of wounds are
      both diverse and contentious. One agent that has been utilized for centuries for
      the treatment of dermatological disorders and possesses a number of
      pharmacological actions that are conducive to wound healing is Calendula
      officinalis, or pot marigold. To assess the effect of Calendula on wound healing,
      a systematic review of the literature was conducted. The search was limited to
      randomized controlled trials that used topically administered monopreparations of
      Calendula officinalis for wounds of any type. Although 6 trials were identified,
      only 1 trial was of good quality; hence, the statistical pooling of results was
      not appropriate. Therefore, a narrative review of these studies was conducted
      indicating that there is only weak evidence to support the topical administration
      of Calendula in acute and chronic wounds. Undoubtedly, further investigation is
      needed to establish whether Calendula has a place in mainstream wound care. 

PMID- 25941794
TI  -  Peripheral Arterial Perfusion: Is it Adequate for Wound Healing     ?
AB  - Peripheral arterial occlusive disease (PAOD) can seriously inhibit or prevent
      healing of lower extremity and foot ulcerations. The history and physical
      findings consistent with PAOD are reviewed and the typical characteristics of
      ischemic, venous, and neuropathic ulcerations are compared and contrasted.
      Noninvasive diagnostic testing techniques currently used to confirm the diagnosis
      of PAOD are summarized. 

PMID- 25941796
TI  - Mechanisms of Acquired Resistance to ALK Inhibitors and the Rationale for
      Treating ALK-positive Lung Cancer.
AB  - The discovery of an echinoderm microtubule-associated protein-like 4 (EML4)
      anaplastic lymphoma kinase (ALK) fusion gene led to improved clinical outcomes in
      patients with lung cancer after the development of the first ALK-targeting agent,
      crizotinib. Some second-generation ALK tyrosine kinase inhibitors (TKIs), which
      might be more potent than crizotinib or effective on crizotinib-resistant
      patients, have been developed. Although these ALK-TKIs show an excellent response
      initially, most patients eventually acquire resistance. Therefore, careful
      consideration of the resistance mechanisms might lead to superior therapeutic
      strategies. Here, we summarize the history of ALK-TKIs and their underlying
      resistance mechanisms in both the preclinical and clinical settings. In addition,
      we discuss potential future treatment strategies in ALK-TKI-naive and -resistant
      patients with lung cancer harboring the EML4-ALK fusion gene. 

PMID- 25941797
TI  - Macro-to-micro cortical vascular imaging underlies regional differences in
      ischemic brain.
AB  - The ability to non-invasively monitor and quantify hemodynamic responses down to
      the capillary level is important for improved diagnosis, treatment and management
      of neurovascular disorders, including stroke. We developed an integrated multi
      functional imaging system, in which synchronized dual wavelength laser speckle
      contrast imaging (DWLS) was used as a guiding tool for optical microangiography
      (OMAG) to test whether detailed vascular responses to experimental stroke in male
      mice can be evaluated with wide range sensitivity from arteries and veins down to
      the capillary level. DWLS enabled rapid identification of cerebral blood flow
      (CBF), prediction of infarct area and hemoglobin oxygenation over the whole mouse
      brain and was used to guide the OMAG system to hone in on depth information
      regarding blood volume, blood flow velocity and direction, vascular architecture,
      vessel diameter and capillary density pertaining to defined regions of CBF in
      response to ischemia. OMAG-DWLS is a novel imaging platform technology to
      simultaneously evaluate multiple vascular responses to ischemic injury, which can
      be useful in improving our understanding of vascular responses under pathologic
      and physiological conditions, and ultimately facilitating clinical diagnosis,
      monitoring and therapeutic interventions of neurovascular diseases. 

PMID- 25941795
TI  - Lymphoma: immune evasion strategies.
AB  - While the cellular origin of lymphoma is often characterized by chromosomal
      translocations and other genetic aberrations, its growth and development into a
      malignant neoplasm is highly dependent upon its ability to escape natural host
      defenses. Neoplastic cells interact with a variety of non-malignant cells in the
      tumor milieu to create an immunosuppressive microenvironment. The resulting
      functional impairment and dysregulation of tumor-associated immune cells not only
      allows for passive growth of the malignancy but may even provide active growth
      signals upon which the tumor subsequently becomes dependent. In the past decade,
      the success of immune checkpoint blockade and adoptive cell transfer for relapsed
      or refractory lymphomas has validated immunotherapy as a possible treatment
      cornerstone. Here, we review the mechanisms by which lymphomas have been found to
      evade and even reprogram the immune system, including alterations in surface
      molecules, recruitment of immunosuppressive subpopulations, and secretion of anti
      inflammatory factors. A fundamental understanding of the immune evasion
      strategies utilized by lymphomas may lead to better prognostic markers and guide
      the development of targeted interventions that are both safer and more effective
      than current standards of care. 

PMID- 25941798
TI  - Toward a quantitative understanding of symmetry reduction involved in the seed
      mediated growth of Pd nanocrystals.
AB  - We report a quantitative analysis of the symmetry reduction phenomenon involved
      in the seed-mediated growth of Pd nanocrystals under dropwise addition of a
      precursor solution. In addition to the elimination of self-nucleation, the
      dropwise approach allows for the formation of a steady state for the number of
      precursor ions in the growth solution, which only fluctuates in a narrow range
      defined by experimental parameters such as the initial concentration of precursor
      solution and the injection rate. We can deterministically control the growth mode
      (symmetric vs asymmetric) of a seed by tuning these parameters to quantitatively
      manipulate the reaction kinetics and thus the lower and upper limits that define
      the steady state. We demonstrate that there exists a correlation between the
      growth mode and the lower limit of precursor ions in the steady state of a seed
      mediated growth process. For the first few drops of precursor solution, the
      resultant atoms will only be deposited on a limited number of available sites on
      the seed if the lower limit of the steady state is below a critical value.
      Afterward, the deposition of atoms will be largely confined to these initially
      activated sites to induce symmetry reduction if atom deposition is kept at a
      faster rate than surface diffusion by controlling the lower limit of precursor
      ions in the steady state. Otherwise, the migration of atoms to other regions
      through surface diffusion can access other sites on the surface of a seed and
      thus lead to the switch of growth mode from asymmetric to symmetric. Our study
      suggests that symmetry reduction can only be initiated and retained by keeping
      the atom deposition at a rate slow enough to limit the number of initial
      nucleation sites on a seed but fast enough to beat the surface diffusion process.

PMID- 25941799
TI  - Heterogeneous and homogeneous catalysis for the hydrogenation of carboxylic acid
      derivatives: history, advances and future directions.
AB  - The catalytic reduction of carboxylic acid derivatives has witnessed a rapid
      development in recent years. These reactions, involving molecular hydrogen as the
      reducing agent, can be promoted by heterogeneous and homogeneous catalysts. The
      milestone achievements and recent results by both approaches are discussed in
      this Review. In particular, we focus on the mechanistic aspects of the catalytic
      hydrogenation and highlight the bifunctional nature of the mechanism that is
      preferred for supported metal catalysts as well as homogeneous transition metal
      complexes. 

PMID- 25941800
TI  - A Data Mining Approach for Examining Predictors of Physical Activity Among Urban
      Older Adults.
AB  - The current study applied innovative data mining techniques to a community survey
      dataset to develop prediction models for two aspects of physical activity (i.e.,
      active transport and screen time) in a sample of urban, primarily Hispanic, older
      adults (N=2,514). Main predictors for active transport (accuracy=69.29%,
      precision=0.67, recall=0.69) were immigrant status, high level of anxiety, having
      a place for physical activity, and willingness to make time for physical
      activity. The main predictors for screen time (accuracy=63.13%, precision=0.60,
      recall=0.63) were willingness to make time for exercise, having a place for
      exercise, age, and availability of family support to access health information on
      the Internet. Data mining methods were useful to identify intervention targets
      and inform design of customized interventions.

PMID- 25941801
TI  - [Hormone therapy in menopause can increase the risk of ovarian cancer].
AB  - Risk of ovarian cancer should be added to the list of adverse effects of hormone
      replacement therapy (HRT). However there is no need for change in clinical
      recommendations. The recommendation today is to prescribe the lowest dose and
      shortest time of HRT for menopausal symptom relief. Our clinical approach should
      be to include among other risk factors the risk of one extra case of ovarian
      cancer/1000 users for 5 years of HRT versus reduced quality of life without HRT
      for each woman.

PMID- 25941802
TI  - [Not Available].

PMID- 25941803
TI  - [MDPV: new drug of abuse that has come to stay?].

PMID- 25941804
TI  - [Sweden needs guidelines for independent medical evaluations].

PMID- 25941805
TI  - Household catastrophic healthcare expenditure and impoverishment due to rotavirus
      gastroenteritis requiring hospitalization in Malaysia.
AB  - BACKGROUND: While healthcare costs for rotavirus gastroenteritis requiring
      hospitalization may be burdensome on households in Malaysia, exploration on the
      distribution and catastrophic impact of these expenses on households are lacking.
      OBJECTIVES: We assessed the economic burden, levels and distribution of
      catastrophic healthcare expenditure, the poverty impact on households and
      inequities related to healthcare payments for acute gastroenteritis requiring
      hospitalization in Malaysia. METHODS: A two-year prospective, hospital-based
      study was conducted from 2008 to 2010 in an urban (Kuala Lumpur) and rural (Kuala
      Terengganu) setting in Malaysia. All children under the age of 5 years admitted
      for acute gastroenteritis were included. Patients were screened for rotavirus and
      information on healthcare expenditure was obtained. RESULTS: Of the 658 stool
      samples collected at both centers, 248 (38%) were positive for rotavirus. Direct
      and indirect costs incurred were significantly higher in Kuala Lumpur compared
      with Kuala Terengganu (US$222 Vs. US$45; p<0.001). The mean direct and indirect
      costs for rotavirus gastroenteritis consisted 20% of monthly household income in
      Kuala Lumpur, as compared with only 5% in Kuala Terengganu. Direct medical costs
      paid out-of-pocket caused 141 (33%) households in Kuala Lumpur to experience
      catastrophic expenditure and 11 (3%) households to incur poverty. However in
      Kuala Terengganu, only one household (0.5%) experienced catastrophic healthcare
      expenditure and none were impoverished. The lowest income quintile in Kuala
      Lumpur was more likely to experience catastrophic payments compared to the
      highest quintile (87% vs 8%). The concentration index for out-of-pocket
      healthcare payments was closer to zero at Kuala Lumpur (0.03) than at Kuala
      Terengganu (0.24). CONCLUSIONS: While urban households were wealthier, healthcare
      expenditure due to gastroenteritis had more catastrophic and poverty impact on
      the urban poor. Universal rotavirus vaccination would reduce both disease burden
      and health inequities in Malaysia.

PMID- 25941806
TI  - Effect of blood vessel segmentation on the outcome of electroporation-based
      treatments of liver tumors.
AB  - Electroporation-based treatments rely on increasing the permeability of the cell
      membrane by high voltage electric pulses applied to tissue via electrodes. To
      ensure that the whole tumor is covered with sufficiently high electric field,
      accurate numerical models are built based on individual patient anatomy.
      Extraction of patient's anatomy through segmentation of medical images inevitably
      produces some errors. In order to ensure the robustness of treatment planning, it
      is necessary to evaluate the potential effect of such errors on the electric
      field distribution. In this work we focus on determining the effect of errors in
      automatic segmentation of hepatic vessels on the electric field distribution in
      electroporation-based treatments in the liver. First, a numerical analysis was
      performed on a simple 'sphere and cylinder' model for tumors and vessels of
      different sizes and relative positions. Second, an analysis of two models
      extracted from medical images of real patients in which we introduced variations
      of an error of the automatic vessel segmentation method was performed. The
      results obtained from a simple model indicate that ignoring the vessels when
      calculating the electric field distribution can cause insufficient coverage of
      the tumor with electric fields. Results of this study indicate that this effect
      happens for small (10 mm) and medium-sized (30 mm) tumors, especially in the
      absence of a central electrode inserted in the tumor. The results obtained from
      the real-case models also show higher negative impact of automatic vessel
      segmentation errors on the electric field distribution when the central electrode
      is absent. However, the average error of the automatic vessel segmentation did
      not have an impact on the electric field distribution if the central electrode
      was present. This suggests the algorithm is robust enough to be used in creating
      a model for treatment parameter optimization, but with a central electrode. 

PMID- 25941807
TI  - Cellular and Subcellular Immunohistochemical Localization and Quantification of
      Cadmium Ions in Wheat (Triticum aestivum).
AB  - The distribution of metallic ions in plant tissues is associated with their
      toxicity and is important for understanding mechanisms of toxicity tolerance. A
      quantitative histochemical method can help advance knowledge of cellular and
      subcellular localization and distribution of heavy metals in plant tissues. An
      immunohistochemical (IHC) imaging method for cadmium ions (Cd2+) was developed
      for the first time for the wheat Triticum aestivum grown in Cd2+-fortified soils.
      Also, 1-(4-Isothiocyanobenzyl)-ethylenediamine-N,N,N,N-tetraacetic acid (ITCB
      EDTA) was used to chelate the mobile Cd2+. The ITCB-EDTA/Cd2+ complex was fixed
      with proteins in situ via the isothiocyano group. A new Cd2+-EDTA specific
      monoclonal antibody, 4F3B6D9A1, was used to locate the Cd2+-EDTA protein complex.
      After staining, the fluorescence intensities of sections of Cd2+-positive roots
      were compared with those of Cd2+-negative roots under a laser confocal scanning
      microscope, and the location of colloidal gold particles was determined with a
      transmission electron microscope. The results enable quantification of the Cd2+
      content in plant tissues and illustrate Cd2+ translocation and cellular and
      subcellular responses of T. aestivum to Cd2+ stress. Compared to the conventional
      metal-S coprecipitation histochemical method, this new IHC method is
      quantitative, more specific and has less background interference. The subcellular
      location of Cd2+ was also confirmed with energy-dispersive X-ray microanalysis.
      The IHC method is suitable for locating and quantifying Cd2+ in plant tissues and
      can be extended to other heavy metallic ions. 

PMID- 25941808
TI  - IL10 Variant g.5311A Is Associated with Visceral Leishmaniasis in Indian
      Population.
AB  - BACKGROUND: Visceral leishmaniasis (VL) is a multifactorial disease, where the
      host genetics play a significant role in determining the disease outcome. The
      immunological role of anti-inflammatory cytokine, Interleukin 10 (IL10), has been
      well-documented in parasite infections and considered as a key regulatory
      cytokine for VL. Although VL patients in India display high level of IL10 in
      blood serum, no genetic study has been conducted to assess the VL susceptibility
      / resistance. Therefore, the aim of this study is to investigate the role of IL10
      variations in Indian VL; and to estimate the distribution of disease associated
      allele in diverse Indian populations. METHODOLOGY: All the exons and exon-intron
      boundaries of IL10 were sequenced in 184 VL patients along with 172 ethnically
      matched controls from VL endemic region of India. RESULT AND DISCUSSION: Our
      analysis revealed four variations; rs1518111 (2195 A>G, intron), rs1554286 (2607
      C>T, intron), rs3024496 (4976 T>C, 3' UTR) and rs3024498 (5311 A>G, 3' UTR). Of
      these, a variant g.5311A is significantly associated with VL (chi2=18.87; p
      =0.00001). In silico approaches have shown that a putative micro RNA binding site
      (miR-4321) is lost in rs3024498 mRNA. Further, analysis of the above four
      variations in 1138 individuals from 34 ethnic populations, representing different
      social and linguistic groups who are inhabited in different geographical regions
      of India, showed variable frequency. Interestingly, we have found, majority of
      the tribal populations have low frequency of VL ('A' of rs3024498); and high
      frequency of leprosy ('T' of rs1554286), and Behcet's ('A' of rs1518111)
      associated alleles, whereas these were vice versa in castes. Our findings suggest
      that majority of tribal populations of India carry the protected / less severe
      allele against VL, while risk / more severe allele for leprosy and Behcet's
      disease. This study has potential implications in counseling and management of VL
      and other infectious diseases.

PMID- 25941810
TI  - Consumption of calcium-fortified cereal bars to improve dietary calcium intake of
      healthy women: randomized controlled feasibility study.
AB  - Calcium is an important structural component of the skeletal system. Although an
      adequate intake of calcium helps to maintain bone health and reduce the risk of
      osteoporosis, many women do not meet recommended daily intakes of calcium.
      Previous interventions studies designed to increase dietary intake of women have
      utilized primarily dairy sources of calcium or supplements. However, lactose
      intolerance, milk protein allergies, or food preferences may lead many women to
      exclude important dairy sources of dietary calcium. Therefore, we undertook a 9
      week randomized crossover design trial to examine the potential benefit of
      including a non-dairy source of calcium in the diet of women. Following a 3 week
      run-in baseline period, 35 healthy women > 18 years were randomized by crossover
      design into either Group I or Group II. Group I added 2 calcium-fortified cereal
      bars daily (total of 400 mg calcium/day) (intervention) to their usual diet and
      Group II continued their usual diet (control). At the end of 3 weeks, diets were
      switched for another 3 weeks. Intakes of calcium and energy were estimated from 3
      day diet and supplemental diaries. Wilcoxon signed-rank tests were used for
      within group comparisons and Mann Whitney U tests were used for between group
      comparisons of calcium and energy intake. Dietary calcium was significantly
      higher during intervention (1071 mg/d) when participants consumed 2 calcium
      fortified cereal bars daily than during the baseline (720 mg/d, P <0.0001) or
      control diets (775 mg/d, P = 0.0001) periods. Furthermore, the addition of 2
      calcium-fortified cereal bars daily for the 3 week intervention did not
      significantly increase total energy intake or result in weight gain. In
      conclusion, consumption of calcium-fortified cereal bars significantly increased
      calcium intake of women. Further research examining the potential ability of
      fortified cereal bars to help maintain and improve bone health of women is
      warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT01508689.

PMID- 25941809
TI  - Group Selection and Contribution of Minority Variants during Virus Adaptation
      Determines Virus Fitness and Phenotype.
AB  - Understanding how a pathogen colonizes and adapts to a new host environment is a
      primary aim in studying emerging infectious diseases. Adaptive mutations arise
      among the thousands of variants generated during RNA virus infection, and
      identifying these variants will shed light onto how changes in tropism and
      species jumps can occur. Here, we adapted Coxsackie virus B3 to a highly
      permissive and less permissive environment. Using deep sequencing and
      bioinformatics, we identified a multi-step adaptive process to adaptation
      involving residues in the receptor footprints that correlated with receptor
      availability and with increase in virus fitness in an environment-specific
      manner. We show that adaptation occurs by selection of a dominant mutation
      followed by group selection of minority variants that together, confer the
      fitness increase observed in the population, rather than selection of a single
      dominant genotype. 

PMID- 25941811
TI  - Clinical Application of Plant Sterol and Stanol Products.
AB  - Plant sterols and stanols (PS) are natural, non-nutritive compounds that play
      important structural roles in plant membranes and abound in seeds and oils
      derived from them. Because they act within the intestinal lumen and undergo
      minimal absorption into the enterocytes, PS are non-systemic agents. Their
      physiological role in plants, natural origin, and non-systemic action, together
      with their proven capacity to lower serum total and LDL-cholesterol, make them
      quite attractive as non-pharmacological agents for the treatment of
      hypercholesterolemia. Recent meta-analyses have summarized the results of >100
      randomized clinical trials and have clearly established that LDL-cholesterol is
      reduced by 9-12% with consumption of PS-fortified foods in different formats at
      doses of 2-3 g per day. PS are effective and safe cholesterol-lowering agents
      with many clinical applications: adjuncts to a healthy diet, common
      hypercholesterolemia, combination treatment with statins, metabolic syndrome, and
      diabetes. The cholesterol-lowering efficacy appears to be similar in all clinical
      situations. PS are also ideal agents to treat hypercholesterolemic children who
      are still not candidates to statin therapy or receive only low-dose statins. In
      the setting of statin treatment, the expected LDL-cholesterol reduction with PS
      is equivalent to up titrating twice the statin dose. There is not enough
      information on the efficacy of PS as add-on therapy to ezetimibe, fibrates, or
      bile acid binding resins. Attesting to the consistent scientific evidence on the
      cholesterol-lowering efficacy and safety of functional foods supplemented with
      PS, several national and international clinical societies have endorsed their use
      as adjuncts to a healthy diet. 

PMID- 25941812
TI  - Organic matter degradation drives benthic cyanobacterial mat abundance on
      Caribbean coral reefs.
AB  - Benthic cyanobacterial mats (BCMs) are impacting coral reefs worldwide. However,
      the factors and mechanisms driving their proliferation are unclear. We conducted
      a multi-year survey around the Caribbean island of Curacao, which revealed
      highest BCM abundance on sheltered reefs close to urbanised areas. Reefs with
      high BCM abundance were also characterised by high benthic cover of macroalgae
      and low cover of corals. Nutrient concentrations in the water-column were
      consistently low, but markedly increased just above substrata (both sandy and
      hard) covered with BCMs. This was true for sites with both high and low BCM
      coverage, suggesting that BCM growth is stimulated by a localised, substrate
      linked release of nutrients from the microbial degradation of organic matter.
      This hypothesis was supported by a higher organic content in sediments on reefs
      with high BCM coverage, and by an in situ experiment which showed that BCMs grew
      within days on sediments enriched with organic matter (Spirulina). We propose
      that nutrient runoff from urbanised areas stimulates phototrophic blooms and
      enhances organic matter concentrations on the reef. This organic matter is
      transported by currents and settles on the seabed at sites with low
      hydrodynamics. Subsequently, nutrients released from the organic matter
      degradation fuel the growth of BCMs. Improved management of nutrients generated
      on land should lower organic loading of sediments and other benthos (e.g. turf
      and macroalgae) to reduce BCM proliferation on coral reefs. 

PMID- 25941813
TI  - A single fas gene mutation changes lupus onset, severity, location, and molecular
      abnormalities in mice.
AB  - Although genetic predisposition plays a major role in the progression of systemic
      lupus erythematosus (SLE) and its variation in symptoms, the precise
      relationships between genetic changes and disease status are not well understood.
      Here, to demonstrate the effect of a single gene mutation on disease etiology, we
      examined two mouse models of SLE with the same genetic background but different
      Fas genes. Mice with the Fas(lpr) gene developed severe SLE with renal
      dysfunction and inflammatory responses in the lung and kidney. By contrast, mice
      with the Fas(+) gene showed disease-related abnormalities in the liver and
      joints. Patterns of inflammatory disease markers differed across organs between
      the two lines of mice. Fas(lpr) mice showed greater MMP signals in the kidney and
      IL-11 signals in the lung than Fas(+) mice. Fas(+) mice had higher IL-11 signal
      intensity in the knee region and higher CXCR4 signal intensity in the liver than
      Fas(lpr) mice. Our results exemplify the complexity of disease and suggest the
      need for individualized target-specific treatment regimens. Strengths and
      Limitations of this Study: Fas gene is a well characterized gene in this disease.
      The molecular components in human disease need more clinical data. 

PMID- 25941814
TI  - Numb induces e-cadherin adhesion dissolution, cytoskeleton reorganization, and
      migration in tubular epithelial cells contributing to renal fibrosis.
AB  - Numb, an endocytic protein, is involved in both neural differentiation and
      protein post-endocytic trafficking. Although negative Numb expression has been
      linked to human mammary carcinomas, little is known about its expression and
      functions in other diseases. In the present study, we observed that Numb is
      expressed in renal tubule epithelia and its expression is increased in the
      fibrotic kidney in vivo. We determined that in proximal tubular epithelial cells
      (NRK52E cells), TGF-beta1 induces the expression of Numb and ectopic expression
      of Numb leads to dissolution of E-cadherin adhesion, reorganization of
      cytoskeleton, activation of Rac1 and Cdc42, and enhancement of migration. Either
      knockdown of alpha-adaptin or overexpression of Numb asparagine-proline
      phenylalanine (NPF) mutant interferes with AP-2 dependent endocytosis and rescues
      Ecadherin level in NRK52E cells. Moreover, knockdown of integrin beta1 or alpha
      adaptin, and overexpression of a Numb dominant-negative form (Numb
      phosphotyrosine binding [PTB] domain) impair integrin endocytosis, and markedly
      inhibit Numb-induced cell migration and activation of Rac1 and Cdc42. Taken
      together, our work identifies Numb as an important player in renal fibrosis, by
      regulating epithelial-to-mesenchymal transition (EMT) process including E
      cadherin adhesion dissolution, actin reorganization, and migration enhancement in
      NRK52E cells. 

PMID- 25941815
TI  - KRAS Mutations in Lung Adenocarcinoma: Molecular and Epidemiological
      Characteristics, Methods for Detection, and Therapeutic Strategy Perspectives.
AB  - KRAS mutations are detected in over one third of lung adenocarcinomas, most
      frequently in Caucasian and smoker patients. The impact of KRAS mutations on lung
      adenocarcinoma prognosis is currently subject to debate, as is their impact on
      the response to chemotherapy and EGFR tyrosine kinase inhibitors. The different
      methods for KRAS status assessment, based on histological and cytological samples
      or biological fluids, offer varying sensitivities. Since no treatments are
      available in clinical routine for KRAS-mutated lung cancer patients, one of the
      current major challenges in thoracic oncology is developing new dedicated
      strategic therapies. Different molecules can be developed that act on a post
      transcriptional KRAS protein level, blocking its cytoplasmic membrane
      recruitment. The efficacy of these molecules' targeting of the different
      signaling pathways activated by the KRAS mutation (such as the MEK and BRAF
      pathways) is related to the particular KRAS mutation subtype. New therapeutic
      strategies are currently focused on certain genes linked with KRAS inducing a
      synthetic lethal interaction. The purpose of this work is to provide an overview
      of i) the recent epidemiological and molecular findings concerning KRASmutated
      lung adenocarcinoma, ii) the prognostic impact of KRAS mutations, in particular
      during response to treatment, iii) the available methods for detecting this
      mutation, and iv) the current molecules under development for new therapeutic
      strategies and the clinical trials targeting this genomic alteration. 

PMID- 25941816
TI  - Ellagic Acid Enhances the Efficacy of PI3K Inhibitor GDC-0941 in Breast Cancer
      Cells.
AB  - The fact that the phosphatidylinositol 3 kinase (PI3K) signaling pathway is one
      of the most frequently deregulated signaling networks has triggered intensive
      efforts in the development of PI3K pathway inhibitors. However, recent clinical
      trial data have shown only limited activity of PI3K inhibitors at tolerated
      doses. Thus, there is an urgent need to identify rational combination therapy to
      improve the efficacy of PI3K-targeted cancer treatment. In this study, we
      investigated if dietary compound ellagic acid (EA) could improve the therapeutic
      efficacy of PI3K inhibitor GDC-0941 in breast cancer. Specifically, using a panel
      of breast cancer cell lines, we showed that combined use of EA and GDC-0941
      significantly inhibited cell growth under attached and detached conditions,
      blocked migration and invasion in vitro as well as tumor initiation and
      metastasis in vivo. Furthermore, we found that EA promoted apoptosis and further
      reduced AKT/mTOR activation in GDC-0941- treated breast cancer cells. Together,
      our data suggest that EA may be a safe and effective agent to boost the efficacy
      of PI3K-directed breast cancer therapy and that such drug combination may merit
      further clinical investigation. 

PMID- 25941817
TI  - Celastrol inhibits inflammatory stimuli-induced neutrophil extracellular trap
      formation.
AB  - Neutrophil extracellular traps (NETs) are web-like structures released by
      activated neutrophils. Recent studies suggest that NETs play an active role in
      driving autoimmunity and tissue injury in diseases including rheumatoid arthritis
      (RA) and systemic lupus erythematosus (SLE). The purpose of this study was to
      investigate if celastrol, a triterpenoid compound, can inhibit NET formation
      induced by inflammatory stimuli associated with RA and SLE. We found that
      celastrol can completely inhibit neutrophil oxidative burst and NET formation
      induced by tumor necrosis factor alpha (TNFalpha) with an IC50 of 0.34 uM and by
      ovalbumin:anti-ovalbumin immune complexes (Ova IC) with an IC50 of 1.53 uM.
      Celastrol also completely inhibited neutrophil oxidative burst and NET formation
      induced by immunoglobulin G (IgG) purified from RA and SLE patient sera. Further
      investigating into the mechanisms, we found that celastrol treatment
      downregulated the activation of spleen tyrosine kinase (SYK) and the concomitant
      phosphorylation of mitogen-activated protein kinase kinase (MAPKK/MEK),
      extracellular-signal-regulated kinase (ERK), and NFkappaB inhibitor alpha
      (IkappaBalpha), as well as citrullination of histones. Our data reveals that
      celastrol potently inhibits neutrophil oxidative burst and NET formation induced
      by different inflammatory stimuli, possibly through downregulating the SYK-MEK
      ERK-NFkappaB signaling cascade. These results suggest that celastrol may have
      therapeutic potentials for the treatment of inflammatory and autoimmune diseases
      involving neutrophils and NETs. 

PMID- 25941818
TI  - Cell metabolism under microenvironmental low oxygen tension levels in stemness,
      proliferation and pluripotency.
AB  - Hypoxia is defined as a reduction in oxygen supply to a tissue below
      physiological levels. However, physiological hypoxic conditions occur during
      early embryonic development; and in adult organisms, many cells such as bone
      marrow stem cells are located within hypoxic niches. Thus, certain processes take
      place in hypoxia, and recent studies highlight the relevance of hypoxia in stem
      cell cancer physiology. Cellular response to hypoxia depends on hypoxia-inducible
      factors (HIFs), which are stabilized under low oxygen conditions. In a hypoxic
      context, various inducible HIF alpha subunits are able to form dimers with
      constant beta subunits and bind the hypoxia response elements (HRE) in the
      genome, acting as transcription factors, inducing a wide variety of gene
      expression. Typically, the HIF pathway has been shown to enhance vascular
      endothelial growth factor (VEGF) expression, which would be responsible for
      angiogenesis and, therefore, re-oxygenation of the hypoxic sites. Embryonic stem
      cells inhibit a severely hypoxic environment, which dictates their glycolytic
      metabolism, whereas differentiated cells shift toward the more efficient aerobic
      respiration for their metabolic demands. Accordingly, low oxygen tension levels
      have been reported to enhance induced pluripotent stem cell (iPS) generation.
      HIFs have also been shown to enhance pluripotency-related gene expression,
      including Oct4 (Octamer-binding transcription factor 4), Nanog and Wnt.
      Therefore, cell metabolism might play a role in stemness maintenance,
      proliferation and cell reprogramming. Moreover, in the hypoxic microenvironment
      of cancer cells, metabolism shifts from oxidative phosphorylation to anaerobic
      glycolysis, a process known as the Warburg effect, which is involved in cancer
      progression and malignancy. 

PMID- 25941819
TI  - Molecular genetics of polycystic ovary syndrome: an update.
AB  - Polycystic ovary syndrome (PCOS) is a complex genetic disorder caused by
      interplay between several 'susceptibility' genes and environment factors. In the
      past few years, numerous studies of genomics and transcriptomics attempted to
      discover genes affecting PCOS. Pre-genome wide association study (GWAS) plays a
      stepping stone effect on the progress of PCOS, even though most of the strongest
      associations are for loci rather than functional variants. A trend towards large
      scale GWAS has succeeded in identifying many additional novel PCOS loci. Most of
      the PCOS-associated regions are shared with other diseases or symptoms, as well
      as with metabolism, inflammation or insulin signaling-related traits, or cancer.
      Moreover, susceptibility genes for early diagnosis of PCOS are expected to offer
      the prevention of long-term risk of obesity, cardiovascular disease, and type 2
      diabetes (T2DM) as well. Furthermore, considerable advanced new technical
      approaches such as GWAS and next-generation sequencing will provide new
      opportunities in the molecular analysis of PCOS, which can, in the long term,
      lead to new therapeutic treatments for the disorder. The present review discusses
      heterogeneous clinical manifestations of PCOS, controversies surrounding the
      diagnosis of PCOS, and the recent findings of pre-GWAS and GWAS studies on PCOS,
      highlighting the relevant candidate gene families and their potential functional
      pathways relevant for PCOS. 

PMID- 25941820
TI  - Membrane Fusion Mediated Targeted Cytosolic Drug Delivery Through scFv Engineered
      Sendai Viral Envelopes.
AB  - Antibody targeted cytoplasmic delivery of drugs is difficult to achieve as
      antigen-antibody interaction results in the payload being directed to the
      endosomal compartment. However, Sendai viral envelopes can bring about
      cytoplasmic delivery due to F-protein mediated membrane fusion. In this study we
      have generated and fused a recombinant scFv directed to the onco-fetal antigen,
      the Placental isozyme of Alkaline Phosphatase (PAP) with the trans-membrane and
      part of the cytoplasmic domain of the Sendai F protein (F(TMC)). Reconstituted
      virosomes, having both the fusion protein as well as the native F-protein were
      able to specifically bind and deliver drugs to PAP expressing cells. About 75% of
      the delivery was cytoplasmic in nature. Hence, this immuno-virosome, which is
      devoid of the comparatively more toxic HN protein, has the novel ability to
      combine specific antibody mediated targeting with cytoplasmic delivery. The scFv
      ensured specific binding to PAP expressing cells, without cross reacting with the
      other isozymes of alkaline phosphatase. The advantages of cytoplasmic delivery
      would include reduced degradation and lowered immunogenicity of the payload and
      carrier. The ubiquitous expression of PAP on a variety of cancers like seminoma,
      choriocarcinoma, cervical and breast cancers also suggests its potential
      usefulness in a number of malignancies. 

PMID- 25941821
TI  - Application of resveratrol in diabetes: rationale, strategies and challenges.
AB  - The increasing prevalence, involvement of several signaling pathways, variable
      pathogenesis, progressive natural history and complications of type 2 diabetes
      emphasize an urgent need for a molecule with multiple actions. Resveratrol
      (3,5,4'-trihydroxy-trans-stilbene) is a polyphenolic antioxidant present in red
      wine gaining a worldwide interest because of its multi-target effect against
      diabetes and other life-threatening diseases. Improving insulin sensitivity,
      enhancing GLUT4 translocation, reducing oxidative stress, regulating carbohydrate
      metabolizing enzymes, activating SIRT1 and AMPK, and decreasing adipogenic genes
      are some promising mechanisms established until now for resveratrol. Apart from
      these, resveratrol attenuates the end organ damage and reduced diabetic
      complications. Resveratrol exerts its beneficial antidiabetic action as evidenced
      from the in vitro, preclinical and clinical studies. Considering all the benefits
      of resveratrol in diabetes, resveratrol based different nutraceutical products
      have been developed commercially to use in humans. However, this compound is
      still under investigation because of some limitations. Resveratrol can be taken
      in to account in the treatment of diabetes after overcoming all hurdles and
      difficulties. This article examines the basic scientific evidences, animal
      experiments, and human/clinical data supporting the antidiabetic action of
      resveratrol and describes the strategies and challenges to recommend resveratrol
      from preclinical to clinical use. 

PMID- 25941822
TI  - Melatonin and male reproductive health: relevance of darkness and antioxidant
      properties.
AB  - The pineal hormone melatonin controls several physiological functions that reach
      far beyond the regulation of the circadian rhythm. Moreover, it can be produced
      in extra-pineal organs such as reproductive organs. The role of melatonin in the
      mammalian seasonal and circadian rhythm is well known. Nevertheless, its overall
      effect in male reproductive physiology remains largely unknown. Melatonin is a
      very powerful endogenous antioxidant that can also be exogenously taken safely.
      Interestingly, its antioxidant properties have been consistently reported to
      improve the male reproductive dysfunctions associated with pathological
      conditions and also with the exposure to toxicants. Nevertheless, the exact
      molecular mechanisms by which melatonin exerts its action in the male
      reproductive system remain a matter of debate. Herein, we propose to present an
      up-to-date overview of the melatonin effects in the male reproductive health and
      debate future directions to disclose possible sites of melatonin action in male
      reproductive system. We will discuss not only the role of melatonin during
      darkness and sleep but also the importance of the antioxidant properties of this
      hormone to male fertility. Since melatonin readily crosses the physiological
      barriers, such as the blood-testis barrier, and has a very low toxicity, it
      appears as an excellent candidate in the prevention and/or treatment of the
      multiple male reproductive dysfunctions associated with various pathologies. 

PMID- 25941823
TI  - Polydatin Restores Endothelium-Dependent Relaxation in Rat Aorta Rings Impaired
      by High Glucose: A Novel Insight into the PPARbeta-NO Signaling Pathway.
AB  - Polydatin, a natural component from Polygonum Cuspidatum, has important
      therapeutic effects on metabolic syndrome. A novel therapeutic strategy using
      polydatin to improve vascular function has recently been proposed to treat
      diabetes-related cardiovascular complications. However, the biological role and
      molecular basis of polydatin's action on vascular endothelial cells (VECs)
      mediated vasodilatation under diabetes-related hyperglycemia condition remain
      elusive. The present study aimed to assess the contribution of polydatin in
      restoring endothelium-dependent relaxation and to determine the details of its
      underlying mechanism. By measuring endothelium-dependent relaxation, we found
      that acetylcholine-induced vasodilation was impaired by elevated glucose (55
      mmol/L); however, polydatin (1, 3, 10 MUmol/L) could restore the relaxation in a
      dose-dependent manner. Polydatin could also improve the histological damage to
      endothelial cells in the thoracic aorta. Polydatin's effects were mediated via
      promoting the expression of endothelial NO synthase (eNOS), enhancing eNOS
      activity and decreasing the inducible NOS (iNOS) level, finally resulting in a
      beneficial increase in NO release, which probably, at least in part, through
      activation of the PPARbeta signaling pathway. The results provided a novel
      insight into polydatin action, via PPARbeta-NO signaling pathways, in restoring
      endothelial function in high glucose conditions. The results also indicated the
      potential utility of polydatin to treat diabetes related cardiovascular diseases.

PMID- 25941824
TI  - Disruption of Transcriptional Coactivator Sub1 Leads to Genome-Wide Re
      distribution of Clustered Mutations Induced by APOBEC in Active Yeast Genes.
AB  - Mutations in genomes of species are frequently distributed non-randomly,
      resulting in mutation clusters, including recently discovered kataegis in tumors.
      DNA editing deaminases play the prominent role in the etiology of these
      mutations. To gain insight into the enigmatic mechanisms of localized
      hypermutagenesis that lead to cluster formation, we analyzed the mutational
      single nucleotide variations (SNV) data obtained by whole-genome sequencing of
      drug-resistant mutants induced in yeast diploids by AID/APOBEC deaminase and base
      analog 6-HAP. Deaminase from sea lamprey, PmCDA1, induced robust clusters, while
      6-HAP induced a few weak ones. We found that PmCDA1, AID, and APOBEC1 deaminases
      preferentially mutate the beginning of the actively transcribed genes.
      Inactivation of transcription initiation factor Sub1 strongly reduced deaminase
      induced can1 mutation frequency, but, surprisingly, did not decrease the total
      SNV load in genomes. However, the SNVs in the genomes of the sub1 clones were re
      distributed, and the effect of mutation clustering in the regions of
      transcription initiation was even more pronounced. At the same time, the mutation
      density in the protein-coding regions was reduced, resulting in the decrease of
      phenotypically detected mutants. We propose that the induction of clustered
      mutations by deaminases involves: a) the exposure of ssDNA strands during
      transcription and loss of protection of ssDNA due to the depletion of ssDNA
      binding proteins, such as Sub1, and b) attainment of conditions favorable for
      APOBEC action in subpopulation of cells, leading to enzymatic deamination within
      the currently expressed genes. This model is applicable to both the initial and
      the later stages of oncogenic transformation and explains variations in the
      distribution of mutations and kataegis events in different tumor cells. 

PMID- 25941825
TI  - NMR structure of the myristylated feline immunodeficiency virus matrix protein.
AB  - Membrane targeting by the Gag proteins of the human immunodeficiency viruses (HIV
      types-1 and -2) is mediated by Gag's N-terminally myristylated matrix (MA) domain
      and is dependent on cellular phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2].
      To determine if other lentiviruses employ a similar membrane targeting mechanism,
      we initiated studies of the feline immunodeficiency virus (FIV), a widespread
      feline pathogen with potential utility for development of human therapeutics.
      Bacterial co-translational myristylation was facilitated by mutation of two amino
      acids near the amino-terminus of the protein (Q5A/G6S; myrMAQ5A/G6S). These
      substitutions did not affect virus assembly or release from transfected cells.
      NMR studies revealed that the myristyl group is buried within a hydrophobic
      pocket in a manner that is structurally similar to that observed for the
      myristylated HIV-1 protein. Comparisons with a recent crystal structure of the
      unmyristylated FIV protein [myr(-)MA] indicate that only small changes in helix
      orientation are required to accommodate the sequestered myr group. Depletion of
      PI(4,5)P2 from the plasma membrane of FIV-infected CRFK cells inhibited
      production of FIV particles, indicating that, like HIV, FIV hijacks the PI(4,5)P2
      cellular signaling system to direct intracellular Gag trafficking during virus
      assembly. 

PMID- 25941827
TI  - The association between pressure ulcers and endothelial dysfunction in a cohort
      of community elderly .
AB  - Vascular disease is a known risk factor for pressure ulcer development, but the
      underlying mechanisms of this association are less established. The authors
      evaluated the relationship between endothelial function (EF) and history of
      pressure ulcers in a nested case-control study of community-dwelling elderly, 60
      years and older. Endothelial function was measured using peripheral arterial
      tonometry, and persons with a history of pressure ulcers in the past 5 years (n =
      7) were matched 2:1 by age and gender to controls with no history of pressure
      ulcers (n = 14). Overall endothelial function was significantly worse in persons
      with pressure ulcers compared to controls (1.32 versus 1.76, respectively; P =
      0.04), and the prevalence of endothelial dysfunction was higher among cases than
      controls as well (100% versus 43%, respectively; P = 0.04). Other vascular risk
      factors were similar in both groups. Endothelial dysfunction appears to be
      associated with pressure ulcer history and may reflect an underlying vascular
      etiology through which ulcer risk is mediated. 

PMID- 25941826
TI  - Baculovirus insecticides in Latin America: historical overview, current status
      and future perspectives.
AB  - Baculoviruses are known to regulate many insect populations in nature. Their host
      specificity is very high, usually restricted to a single or a few closely related
      insect species. They are amongst the safest pesticides, with no or negligible
      effects on non-target organisms, including beneficial insects, vertebrates and
      plants. Baculovirus-based pesticides are compatible with integrated pest
      management strategies and the expansion of their application will significantly
      reduce the risks associated with the use of synthetic chemical insecticides.
      Several successful baculovirus-based pest control programs have taken place in
      Latin American countries. Sustainable agriculture (a trend promoted by state
      authorities in most Latin American countries) will benefit from the wider use of
      registered viral pesticides and new viral products that are in the process of
      registration and others in the applied research pipeline. The success of
      baculovirus-based control programs depends upon collaborative efforts among
      government and research institutions, growers associations, and private
      companies, which realize the importance of using strategies that protect human
      health and the environment at large. Initiatives to develop new regulations that
      promote the use of this type of ecological alternatives tailored to different
      local conditions and farming systems are underway. 

PMID- 25941828
TI  - New Topical Agents for Treatment of Partial-thickness Burns in Children: A
      Review of Published Outcome Studies .
AB  - Evidence-based choices for treating burns in children are not well defined.
      Skin substitutes and contemporary dressings offer potential advantages over
      traditional treatment with topical antimicrobial agents in treating partial
      thickness burns. Newer treatment modalities may reduce morbidity, financial
      burdens, and scarring by accelerating healing. Reports of pediatric burn
      management from 1997 to 2007 were reviewed to compare agent performance with
      outcome measures such as healing time, pain moderation, cosmetic results, and
      hospital costs. TranscyteTM (Smith & Nephew, London), Biobrane(r) (Bertek
      Pharmaceuticals Inc, Morgantown, WV), beta-glucan collagen, and Mepitel(r)
      (Molnlycke, Goteborg, Sweden) have been reported as superior to silver
      sulfadiazine (SSD) in achieving faster healing times and decreased pain in
      pediatric patients. Initial reports describing the outcomes achieved with these
      new agents indicate that they may offer clinical advantages in the treatment of
      partial-thickness burns in children. Increased costs of the new products appeared
      to be offset by decreases in hospital stay, nursing care time and pain
      medications. The existing literature is not conclusive, and prospective trials
      with standardized outcome measures are needed to better define the role of these
      agents.    . 

PMID- 25941829
TI  -  Comparison of two silver dressings for wound management in pediatric burns.
AB  - Purpose. Silver wound dressings are widely used in the treatment of burns.
      Dressings differ in material characteristics, various antimicrobial activities,
      and ease of use. The purpose of this study was to evaluate both dressing
      performance and amount of pain during the dressing changes of 2 silver dressings
      Urgotul SSD(r) (Laboratoires Urgo, Chenove, France), and Contreet Ag(r)
      (Coloplast, Minneapolis, MN) in children. METHODS: A retrospective cohort study
      was performed with 2 groups of 20 burns treated with Urgotul SSD and Contreet Ag
      until the wounds were healed or grafted. Seventy dressing changes in the Contreet
      Ag group and 67 dressing changes in the Urgotul group were evaluated. Every
      dressing change was assessed regarding the dressing performance (exudate,
      adherence, bleeding, and dressing application/removal), and pain. RESULTS: Pain
      was "absent or slight" in 61 (92%) dressing changes with Urgotul SSD, and in 60
      (85%) of the dressing changes with Contreet Ag. Dressing application in the
      Urgotul group was more often "very easy" (n = 33; 49%) or "easy" (n = 32; 48%)
      than in the Contreet Ag group, "very easy" (n = 25; 35%), and "easy" (n = 42;
      60%). Contreet Ag had a greater ability to absorb exudate ("very good" n = 60;
      85%, and "good" n = 11; 15%) than Urgotul SSD ("very good" n = 34; 51%, and
      "good" n = 13; 19%). CONCLUSION: Urgotul SSD and Contreet Ag are comparable
      regarding pain during dressing change. The dressings differ in their ability to
      absorb exudate and ease of application. Both dressings provided nearly painless
      wound management, and therefore were highly accepted by the nurses and especially
      the children being treated.

PMID- 25941830
TI  -  Understanding pain and quality of life for patients with chronic venous ulcers .
AB  - Aim. To identify the impact of pain on quality of life (QOL) of patients with
      chronic venous ulcers. METHODS: A cross-sectional study was performed on 40
      outpatients with chronic venous ulcers who were recruited at one outpatient care
      center in Sao Paulo, Brazil. WHOQOL-Bref was used to assess QOL, the McGill Pain
      Questionnaire-Short Form (MPQ) to identify pain characteristics, and an 11-point
      numerical pain rating scale to measure pain intensity. Kruskall-Wallis or ANOVA
      test, with post-hoc correction (Tukey test) was applied to compare groups.
      Multiple linear regression models were used. RESULTS: The mean age of the
      patients was 67 +/- 11 years (range, 39-95 years), and 26 (65%) were women. The
      prevalence of pain was 90%, with worst pain mean intensity of 6.2 +/- 3.5. Severe
      pain was the most prevalent (21 patients, 52.5%). Pain most frequently reported
      was sensory-discriminative and evaluative in quality. Pain was significantly and
      negatively correlated with physical (PY), environmental (EV), and overall QOL.
      Compared to a no-pain group, those with pain had lower overall QOL. On multiple
      analyses, pain remained as a predictor of overall QOL (b = -0.73, P = 0.03) and
      was also predictive of social QOL, whereas pain did not have any impact on
      physical, emotional, or social relationships QOL (b = -3.85, P = 0.00) when
      adjusted for age, number, duration and frequency of wounds, pain dimension (MPQ),
      partnership, and economic status. CONCLUSION: To improve QOL of outpatients with
      chronic venous ulcers, the qualities and the intensity of pain must be considered
      differently.

PMID- 25941831
TI  -  Complex wound management with an artificial dermal regeneration template   .
AB  - The following case reports on the successful use of Integra(r) (Integra
      LifeSciences, Plainsboro, NJ) as an alternative for coverage of exposed tibia in
      a patient with necrotizing fasciitis and significant comorbidities. Necrotizing
      fasciitis is a generalized term that is used to describe soft tissue infections
      in which necrosis of the fascia and subcutaneous tissue occurs. Necrotizing
      fasciitis will often begin with disproportionate pain, localized erythema, and
      skin discoloration with vesicle formation. As the disease progresses along
      fascial planes, an area of deep necrosis develops with eventual signs of systemic
      toxicity and sepsis. Diagnosis of this condition can be quite challenging, and
      the diagnostic value of laboratory tests is limited. Aggressive treatment of
      necrotizing fasciitis is extremely important; the infection develops rapidly and
      can quickly lead to systemic toxicity and death. Traditionally, management of
      necrotizing fasciitis consists of resuscitation and stabilization of the patient,
      aggressive surgical debridement of all nonviable tissue, and the administration
      of broad-spectrum antibiotics. Reconstructive surgery is indicated for many
      patients who have recovered from necrotizing fasciitis. Integra, an artificial
      dermal regeneration template (DRT), has emerged as an adjunct to split-thickness
      grafts or tissue transfers. This case exemplifies the potential for DRT to
      provide another, more direct alternative for coverage of a complex, exposed
      wound.  . 

PMID- 25941832
TI  - Anaerobic Chemolithotrophic Growth of the Haloalkaliphilic Bacterium Strain MLMS
      1 by Disproportionation of Monothioarsenate.
AB  - A novel chemolithotrophic metabolism based on a mixed arsenic-sulfur species has
      been discovered for the anaerobic deltaproteobacterium, strain MLMS-1, a
      haloalkaliphile isolated from Mono Lake, California, U.S. Strain MLMS-1 is the
      first reported obligate arsenate-respiring chemoautotroph which grows by coupling
      arsenate reduction to arsenite with the oxidation of sulfide to sulfate. In that
      pathway the formation of a mixed arsenic-sulfur species was reported. That
      species was assumed to be monothioarsenite ([H2As(III)S(-II)O2](-)), formed as an
      intermediate by abiotic reaction of arsenite with sulfide. We now report that
      this species is monothioarsenate ([HAs(V)S(-II)O3](2-)) as revealed by X-ray
      absorption spectroscopy. Monothioarsenate forms by abiotic reaction of arsenite
      with zerovalent sulfur. Monothioarsenate is kinetically stable under a wide range
      of pH and redox conditions. However, it was metabolized rapidly by strain MLMS-1
      when incubated with arsenate. Incubations using monothioarsenate confirmed that
      strain MLMS-1 was able to grow (MU = 0.017 h(-1)) on this substrate via a
      disproportionation reaction by oxidizing the thio-group-sulfur (S(-II)) to
      zerovalent sulfur or sulfate while concurrently reducing the central arsenic atom
      (As(V)) to arsenite. Monothioarsenate disproportionation could be widespread in
      nature beyond the already studied arsenic and sulfide rich hot springs and soda
      lakes where it was discovered. 

PMID- 25941833
TI  - Correction to Effect of Silicate on the Formation and Stability of Ni-Al LDH at
      the gamma-Al2O3 Surface.

PMID- 25941835
TI  - Temporal behavior of the singlet molecular oxygen emission in imidazolium and
      morpholinium ionic liquids and its implications.
AB  - The solvent effect of ionic liquids on the lifetime of singlet molecular oxygen,
      O2((1)Deltag), was investigated by means of time-resolved near-IR emission
      spectroscopy. O2((1)Deltag) was generated by photosensitization of methylene blue
      in morpholinium and imidazolium ionic liquids, both comprising various alkyl
      chains of different lengths. The measured time profiles of O2((1)Deltag)
      luminescence for the (1)Deltag -> (3)Sigmag(-) transition were represented by a
      single-exponential decay function. The phosphorescence lifetime was found to be
      correlated with the alkyl chain length of the morpholinium ionic liquids. This
      observation was interpreted by considering efficient quenching of O2((1)Deltag)
      through energy transfer to the high-frequency C-H stretching modes of the N-alkyl
      chain in the morpholinium cation. Interestingly, we found that O2((1)Deltag)
      quenching by the C-H stretching modes of the ring of the cations was remarkably
      depressed. The kinetics of the O2((1)Deltag) emission decay process was discussed
      on the basis of the heterogeneous structure of ionic liquids consisting of polar
      and nonpolar domains. 

PMID- 25941834
TI  - Novel Bifunctional Cyclic Chelator for (89)Zr Labeling-Radiolabeling and
      Targeting Properties of RGD Conjugates.
AB  - Within the last years (89)Zr has attracted considerable attention as long-lived
      radionuclide for positron emission tomography (PET) applications. So far
      desferrioxamine B (DFO) has been mainly used as bifunctional chelating system.
      Fusarinine C (FSC), having complexing properties comparable to DFO, was expected
      to be an alternative with potentially higher stability due to its cyclic
      structure. In this study, as proof of principle, various FSC-RGD conjugates
      targeting alphavbeta3 integrins were synthesized using different conjugation
      strategies and labeled with (89)Zr. In vitro stability, biodistribution, and
      microPET/CT imaging were evaluated using [(89)Zr]FSC-RGD conjugates or
      [(89)Zr]triacetylfusarinine C (TAFC). Quantitative (89)Zr labeling was achieved
      within 90 min at room temperature. The distribution coefficients of the different
      radioligands indicate hydrophilic character. Compared to [(89)Zr]DFO, [(89)Zr]FSC
      derivatives showed excellent in vitro stability and resistance against
      transchelation in phosphate buffered saline (PBS), ethylenediaminetetraacetic
      acid solution (EDTA), and human serum for up to 7 days. Cell binding studies and
      biodistribution as well as microPET/CT imaging experiments showed efficient
      receptor-specific targeting of [(89)Zr]FSC-RGD conjugates. No bone uptake was
      observed analyzing PET images indicating high in vivo stability. These findings
      indicate that FSC is a highly promising chelator for the development of (89)Zr
      based PET imaging agents. 

PMID- 25941836
TI  - Influence of the potential well on the breakage rate of colloidal aggregates in
      simple shear and uniaxial extensional flows.
AB  - In this work we build on our previous paper (Harshe, Y. M.; Lattuada, M. Langmuir
      2012, 28, 283-292) and compute the breakage rate of colloidal aggregates under
      the effect of shear forces by means of Stokesian dynamics simulations. A library
      of clusters made of identical spherical particles covering a broad range of
      masses and fractal dimension values (from 1.8 to 3.0) was generated by means of a
      combination of several Monte Carlo methods. DLVO theory has been used to describe
      the interparticle interactions, and contact forces have been introduced by means
      of the discrete element method. The aggregate breakage process was investigated
      by exposing them to well-defined shear forces, generated under both simple shear
      and uniaxial extensional flow conditions, and by recording the time required to
      reach the first breakage event. It has been found that the breakage rate of
      clusters was controlled by the potential well between particles as described by
      DLVO theory. A semiempirical Arrhenius-type exponential equation that relates the
      potential well to the breakage rate has been used to fit the simulation results.
      The dependence of the breakage process on the radius of gyration, on the external
      shear strength, and on the fractal dimension has been obtained, providing a very
      general relationship for the breakage rate of clusters. It was also found that
      the fragment mass distribution is insensitive to the presence of electrostatic
      repulsive interactions. We also clarify the physical reason for the large
      difference in the breakage rate of clusters between simple shear and the uniaxial
      extensional flow using a criterion based on the energy dissipation rate. Finally,
      in order to answer the question of the minimum cluster size that can break under
      simple shear conditions, a critical rotation number has been introduced,
      expressing the maximum number of rotations that a cluster exposed to simple shear
      could sustain before breakage. 

PMID- 25941837
TI  - Correction to Palladium-catalyzed carbonylative Sonogashira coupling of aryl
      bromides using near stoichiometric carbon monoxide.

PMID- 25941838
TI  - Particle coating-dependent interaction of molecular weight fractionated natural
      organic matter: impacts on the aggregation of silver nanoparticles.
AB  - Ubiquitous natural organic matter (NOM) plays an important role in the
      aggregation state of engineered silver nanoparticles (AgNPs) in aquatic
      environment, which determines the transport, transformation, and toxicity of
      AgNPs. As various capping agents are used as coatings for nanoparticles and NOM
      are natural polymer mixture with wide molecular weight (MW) distribution, probing
      the particle coating-dependent interaction of MW fractionated natural organic
      matter (Mf-NOM) with various coatings is helpful for understanding the
      differential aggregation and transport behavior of engineered AgNPs as well as
      other metal nanoparticles. In this study, we investigated the role of pristine
      and Mf-NOM on the aggregation of AgNPs with Bare, citrate, and PVP coating (Bare
      , Cit-, and PVP-AgNP) in mono- and divalent electrolyte solutions. We observed
      that the enhanced aggregation or dispersion of AgNPs in NOM solution highly
      depends on the coating of AgNPs. Pristine NOM inhibited the aggregation of Bare
      AgNPs but enhanced the aggregation of PVP-AgNPs. In addition, Mf-NOM fractions
      have distinguishing roles on the aggregation and dispersion of AgNPs, which also
      highly depend on the AgNPs coating as well as the MW of Mf-NOM. Higher MW Mf-NOM
      (>100 kDa and 30-100 kDa) enhanced the aggregation of PVP-AgNPs in mono- and
      divalent electrolyte solutions, whereas lower MW Mf-NOM (10-30 kDa, 3-10 kDa and
      <3 kDa) inhibited the aggregation of PVP-AgNPs. However, all the Mf-NOM fractions
      inhibited the aggregation of Bare-AgNPs. For PVP- and Bare-AgNPs, the stability
      of AgNPs in electrolyte solution was significantly correlated to the MW of Mf
      NOM. But for Cit-AgNPs, pristine NOM and Mf-NOM has minor influence on the
      stability of AgNPs. These findings about significantly different roles of Mf-NOM
      on aggregation of engineered AgNPs with various coating are important for better
      understanding of the transport and subsequent transformation of AgNPs in aquatic
      environment. 

PMID- 25941839
TI  - Synthesis of gamma-Acetoxy beta-Keto Esters Through Regioselective Hydration of
      gamma-Acetoxy-alpha,beta-alkynoates.
AB  - The Au(I)-catalyzed regioselective hydration of gamma-acetoxy-alpha,beta
      acetylinic ester by the assistance of a neighboring carbonyl group has been
      developed. Varieties of simple primary, secondary, and tertiary gamma-acetoxy
      alpha,beta-acetylinic esters, even those bearing sensitive functional group in
      the remote reaction sites, are selectively hydrated to the corresponding beta
      keto esters. The reaction tolerates a wide variety of other carboxylates, such as
      benzoates, propionates, acrylates, and pivalates, including chiral carboxylates
      with retention of the configuration. The broad substrate scope, including the
      derivatization of complex natural products and neutral and open air conditions,
      makes this atom economical approach very practical. (18)O labeling experiments
      disclose that the oxygen transposition occurs from the carboxylate group to the
      triple bond, not from water. 

PMID- 25941841
TI  - Contactless Determination of Electrical Conductivity of One-Dimensional
      Nanomaterials by Solution-Based Electro-orientation Spectroscopy.
AB  - Nanowires of the same composition, and even fabricated within the same batch,
      often exhibit electrical conductivities that can vary by orders of magnitude.
      Unfortunately, existing electrical characterization methods are time-consuming,
      making the statistical survey of highly variable samples essentially impractical.
      Here, we demonstrate a contactless, solution-based method to efficiently measure
      the electrical conductivity of 1D nanomaterials based on their transient
      alignment behavior in ac electric fields of different frequencies. Comparison
      with direct transport measurements by probe-based scanning tunneling microscopy
      shows that electro-orientation spectroscopy can quantitatively measure nanowire
      conductivity over a 5-order-of-magnitude range, 10(-5)-1 Omega(-1) m(-1)
      (corresponding to resistivities in the range 10(2)-10(7) Omega.cm). With this
      method, we statistically characterize the conductivity of a variety of nanowires
      and find significant variability in silicon nanowires grown by metal-assisted
      chemical etching from the same wafer. We also find that the active carrier
      concentration of n-type silicon nanowires is greatly reduced by surface traps and
      that surface passivation increases the effective conductivity by an order of
      magnitude. This simple method makes electrical characterization of insulating and
      semiconducting 1D nanomaterials far more efficient and accessible to more
      researchers than current approaches. Electro-orientation spectroscopy also has
      the potential to be integrated with other solution-based methods for the high
      throughput sorting and manipulation of 1D nanomaterials for postgrowth device
      assembly. 

PMID- 25941840
TI  - Postnatal Pancreas of Mice Contains Tripotent Progenitors Capable of Giving Rise
      to Duct, Acinar, and Endocrine Cells In Vitro.
AB  - Postnatal pancreas is a potential source for progenitor cells to generate
      endocrine beta-cells for treating type 1 diabetes. However, it remains unclear
      whether young (1-week-old) pancreas harbors multipotent progenitors capable of
      differentiating into duct, acinar, and endocrine cells. Laminin is an
      extracellular matrix (ECM) protein important for beta-cells' survival and
      function. We established an artificial extracellular matrix (aECM) protein that
      contains the functional IKVAV (Ile-Lys-Val-Ala-Val) sequence derived from laminin
      (designated aECM-lam). Whether IKVAV is necessary for endocrine differentiation
      in vitro is unknown. To answer these questions, we cultured single cells from 1
      week-old pancreas in semi-solid media supplemented with aECM-lam, aECM-scr (which
      contains a scrambled sequence instead of IKVAV), or Matrigel. We found that
      colonies were generated in all materials. Individual colonies were examined by
      microfluidic reverse transcription-polymerase chain reaction, immunostaining, and
      electron microscopy analyses. The majority of the colonies expressed markers for
      endocrine, acinar, and ductal lineages, demonstrating tri-lineage potential of
      individual colony-forming progenitors. Colonies grown in aECM-lam expressed
      higher levels of endocrine markers Insulin1, Insulin2, and Glucagon compared with
      those grown in aECM-scr and Matrigel, indicating that the IKVAV sequence enhances
      endocrine differentiation. In contrast, Matrigel was inhibitory for endocrine
      gene expression. Colonies grown in aECM-lam displayed the hallmarks of functional
      beta-cells: mature insulin granules and glucose-stimulated insulin secretion.
      Colony-forming progenitors were enriched in the CD133(high) fraction and among
      230 micro-manipulated single CD133(high) cells, four gave rise to colonies that
      expressed tri-lineage markers. We conclude that young postnatal pancreas contains
      multipotent progenitor cells and that aECM-lam promotes differentiation of beta
      like cells in vitro. 

PMID- 25941843
TI  - Antimony, Arsenic and Chromium Speciation Studies in Biala Przemsza River (Upper
      Silesia, Poland) Water by HPLC-ICP-MS.
AB  - In this paper the total concentration of As, Cr, Sb, pH and the red-ox potential
      of water and sediment samples of the Biala Przemsza River were determined. The
      arsenic (AB, MMA, DMA, As(III), As(V)), chromium (Cr(III), Cr(VI)) and antimony
      (Sb(III), Sb(V)) forms were studied by HPLC-ICP-MS. Ions were successfully
      separated on Hamilton PRP-X100: (AB, MMA, DMA, As(III), As(V)), Dionex Ion Pac AS
      7 (Sb(III), Sb(V)) and Dionex IonPac AG7 columns: Cr(III), Cr(VI) with LOD 0.16
      MUg/L, 0.08 MUg/L, 0.09 MUg/L, 0.012 MUg/L, 0.08 MUg/L, 0.12 MUg/L, 0.009 MUg/L,
      0.012 MUg/L, 0.19 MUg/L, 0.37 MUg/L, respectively. The simplified BCR three-step
      sequential chemical extraction was performed on the bottom sediment samples. The
      samples were collected monthly, between April and December 2014, at five sampling
      points. Large contents of manganese, lead, cadmium and zinc were found in the
      Biala Przemsza River water. In December 2014, the lead content in the bottom
      sediment in Slawkow was nearly 6000 mg/kg. In the river water, only the inorganic
      arsenic speciation forms were found. Sb(V), As(V) and Cr(III) were dominant.
      Studies have shown that arsenic, antimony and chromium were mainly bound to
      oxides, organic matter and sulphides in the bottom sediments. 

PMID- 25941842
TI  - Preparation of Hollow N-Chloramine-Functionalized Hemispherical Silica Particles
      with Enhanced Efficacy against Bacteria in the Presence of Organic Load:
      Synthesis, Characterization, and Antibacterial Activity.
AB  - The fabrication of highly effective antimicrobial materials is an important
      strategy for coping with the growing concern of bacterial resistance. In this
      study, N-chloramine-functionalized hollow hemispherical structures were designed
      and prepared to examine possible enhancement of antimicrobial performance.
      Antimicrobial testing was carried out on Gram-negative (Escherichia coli) and
      Gram-positive (Baccilus Cereus) bacteria in the presence and absence of
      biological medium. The efficacy of the hollow hemispherical particles
      functionalized with various N-chloramines in killing bacteria was compared among
      themselves with that of small organic molecules and spherical particles to
      investigate the effect of the surface charge, chemical structure, and shape of
      the particles. Results demonstrated that quaternary ammonium salt or amine
      functions in the chemical structure enhanced the antimicrobial activity of the
      particles and made the particles more effective than the small molecules in the
      presence of biological medium. The importance of particle shape in the killing
      tests was also confirmed. 

PMID- 25941845
TI  - Toxicity assessment of refill liquids for electronic cigarettes.
AB  - We analyzed 42 models from 14 brands of refill liquids for e-cigarettes for the
      presence of micro-organisms, diethylene glycol, ethylene glycol, hydrocarbons,
      ethanol, aldehydes, tobacco-specific nitrosamines, and solvents. All the liquids
      under scrutiny complied with norms for the absence of yeast, mold, aerobic
      microbes, Staphylococcus aureus, and Pseudomonas aeruginosa. Diethylene glycol,
      ethylene glycol and ethanol were detected, but remained within limits authorized
      for food and pharmaceutical products. Terpenic compounds and aldehydes were found
      in the products, in particular formaldehyde and acrolein. No sample contained
      nitrosamines at levels above the limit of detection (1 MUg/g). Residual solvents
      such as 1,3-butadiene, cyclohexane and acetone, to name a few, were found in some
      products. None of the products under scrutiny were totally exempt of potentially
      toxic compounds. However, for products other than nicotine, the oral acute
      toxicity of the e-liquids tested seems to be of minor concern. However, a
      minority of liquids, especially those with flavorings, showed particularly high
      ranges of chemicals, causing concerns about their potential toxicity in case of
      chronic oral exposure. 

PMID- 25941846
TI  - Objective analysis of heterologous collagen efficacy in hard-to-heal venous leg
      ulcers.
AB  - Introduction. Collagen plays a major role in tissue repair and is a valid option
      for the treatment of chronic and acute wounds. Collagen speeds fibroblast
      deposition inside the extracellular matrix and stimulates angiogenesis,
      granulation tissue formation, and remodeling. Evaluation of the efficacy of wound
      treatment can be made by noninvasive, objective instrumental assessment.
      MATERIALS AND METHODS: Forty-six patients with venous leg ulcers were enrolled
      into the study. The ulcers showed no clinical signs of healing over the course of
      6 weeks despite standard treatment. Patients in group A were treated with a
      biological dressing made of heterologous collagen (Condress(r), Abiogen Pharma,
      Italy) and with a standard treatment in group B. The duration of the treatment
      was 4 weeks. Chronic wounds were monitored by means of noninvasive assessment
      using a laser scanning system capable of performing 3D evaluation and color
      defragmentation. RESULTS: The median increase in granulation tissue after 4 weeks
      of therapy was 65% in group A compared to 7% in group B (P < 0.001). A median
      reduction of 50% in relative ulcer area was observed in group A after 4 weeks of
      treatment, compared with 32% in group B (P < 0.05). CONCLUSION: This study
      objectively demonstrated that a heterologous collagen biological dressing induced
      granulation tissue in hard-to-heal venous leg ulcers better than standard
      treatment. The scanning system used to monitor lesions was not only fast, but was
      easy to use, and had good intra- and inter-observer reproducibility.

PMID- 25941844
TI  - Where to go from here? An exploratory meta-analysis of the most promising
      approaches to depression prevention programs for children and adolescents.
AB  - OBJECTIVE: To examine the overall effect of individual depression prevention
      programs on future likelihood of depressive disorder and reduction in depressive
      symptoms. In addition, we have investigated whether Cognitive Behavioural Therapy
      (CBT), Interpersonal Therapy (IPT) and other therapeutic techniques may modify
      this effectiveness. METHODS: This study is based on and includes the trial data
      from meta-analyses conducted in the Cochrane systematic review of depression
      prevention programs for children and adolescents by Merry et al. (2011). All
      trials were published or unpublished English language randomized controlled
      trials (RCTs) or cluster RCTs of any psychological or educational intervention
      compared to no intervention to prevent depression in children and adolescents
      aged 5-19 years. RESULTS: There is some evidence that the therapeutic approach
      used in prevention programs modifies the overall effect. CBT is the most studied
      type of intervention for depression prevention, and there is some evidence of its
      effectiveness in reducing the risk of developing a depressive disorder,
      particularly in targeted populations. Fewer studies employed IPT, however this
      approach appears promising. To our knowledge, this is the first study to have
      explored how differences in the approach taken in the prevention programs modify
      the overall treatment effects of prevention programs for children and
      adolescents. CONCLUSIONS: More research is needed to identify the specific
      components of CBT that are most effective or indeed if there are other approaches
      that are more effective in reducing the risk of future depressive episodes. It is
      imperative that prevention programs are suitable for large scale roll-out, and
      that emerging popular modes of delivery, such as online dissemination continue to
      be rigorously tested.

PMID- 25941847
TI  -  Mycologic evaluations in chronic leg ulcers .
AB  - Background. Thus far, the role of fungi in superinfection of chronic leg ulcers
      has been poorly studied. Many articles are based on either a small number of
      patients or single cases. Furthermore, the study conclusions are conflicting.
      OBJECTIVE: The objective of this study was to evaluate the percentage of mycotic
      superinfections and their clinical importance in chronic leg ulcers. METHODS: A
      group of 149 consecutive patients without diabetes was subjected to mycologic
      examination of the ulcers. Two specimens were obtained from each ulcer. RESULTS:
      Mycologic examinations were positive in 11 patients (7.4%). Candida albicans was
      the most frequently isolated species (7 patients), followed by C. parapsilosis (2
      patients), C. krusei (1 patient), C. parapsilosis and C. lipolytica (1 patient).
      Neither dermatophytes nor molds were isolated. No particular features
      characterized the clinical appearance of ulcers superinfected by fungi, and no
      clinical improvement of ulcers with mycotic superinfections was observed with
      oral antimycotic therapy. CONCLUSION: Based on the results of this study,
      mycologic examinations may be considered unnecessary in patients without diabetes
      who suffer with chronic leg ulcers.    .

PMID- 25941848
TI  -     Clinical evaluation of a wound measurement and documentation system.
AB  - Wound measurement is essential in assessing the progress of wound healing. The
      most commonly used tools include wound tracings, width and length measurements,
      and digital photography. These methods have been useful in clinical practice but
      have some limitations, such as lack of accuracy, difficulty of use, and often
      entail wound contact. More advanced equipment tends to be bulky, heavy, and
      expensive. The following reviews the authors' experience with a new wound
      measurement and documentation system, the ARANZ Medical Silhouette MobileTM
      (ARANZ Medical, Christchurch, New Zealand). This innovative device combines a
      digital camera and structured lighting in the form of 2 laser beams to
      automatically correct for image scale and skin curvature, allowing rapid and
      accurate measurements of the wound surface area and depth. The scanner unit plugs
      into a standard personal digital assistant to form a portable device that can be
      easily held and operated using 1 hand. The scanner has been used in clinical
      practice trials in patients with venous leg ulcers, diabetic foot ulcers, and in
      the community setting. The scanner was found to be accurate and reliable, easy to
      learn and use, portable, and compact. The results presented suggest that this
      device may be a viable choice in the management of different types of chronic
      wounds. 

PMID- 25941849
TI  - Instrumental evaluation of the protective effects of a barrier film on
      surrounding skin in chronic wounds.
AB  - Objective. This study investigated the effects of Cavilon(r) No Sting Barrier
      Film ([NSBF], 3M Healthcare, St. Paul, Minn) on skin surrounding chronic wounds
      by means of monitoring transepidermal water loss (TEWL). METHODS: Forty patients
      were examined; 20 patients had pressure ulcers and the other 20 patients had
      venous leg ulcers. The patients were divided into 2 groups, the first group
      (treatment group) was treated with NSBF and the second group (control group) was
      treated with zinc oxide ointment applied to surrounding skin. TEWL values on
      surrounding skin were monitored before and after the therapy. RESULTS:
      Statistical evaluation showed an overall reduction of 45% in TEWL values in both
      groups by the conclusion of the study period when compared to baseline values (P
      < 0.01). The NSBF application was a quick and simple process. Removal of residue
      was not necessary. An additional benefit is that the skin can be seen through the
      film. CONCLUSION: The study objectively demonstrated that the NSBF can help in
      the management of the skin surrounding chronic wounds.

PMID- 25941863
TI  - Tailored Electrospinning of WO3 Nanobelts as Efficient Ultraviolet Photodetectors
      with Photo-Dark Current Ratios up to 1000.
AB  - In this work, polycrystalline WO3 nanobelts were fabricated via an
      electrospinning process combined with subsequent air calcination. The resultant
      products were characterized by X-ray diffraction, field-emission scanning
      electron microscopy, and high-resolution transmission electron microscopy in
      regard to the structures. It has been found that the applied voltage during the
      electrospinning process played the determined role in the formation of the WO3
      nanobelts, allowing the controlled growth of the nanobelts. The ultraviolet (UV)
      photodetector assembled by an individual WO3 nanobelt exhibits a high sensitivity
      and a precise selectivity to the different wavelength lights, with a very low
      dark current and typical photo-dark current ratio up to 1000, which was the
      highest for any WO3 photodectectors ever reported. This work could not only push
      forward the facile preparation of WO3 nanobelts but also represent, for the first
      time, the possibility that the polycrystalline WO3 nanobelts could be a promising
      building block for the highly efficient UV photodetectors. 

PMID- 25941850
TI  - Red Meat and Colorectal Cancer: A Quantitative Update on the State of the
      Epidemiologic Science.
AB  - The potential relationship between red meat consumption and colorectal cancer
      (CRC) has been the subject of scientific debate. Given the high degree of
      resulting uncertainty, our objective was to update the state of the science by
      conducting a systematic quantitative assessment of the epidemiologic literature.
      Specifically, we updated and expanded our previous meta-analysis by integrating
      data from new prospective cohort studies and conducting a broader evaluation of
      the relative risk estimates by specific intake categories. Data from 27
      independent prospective cohort studies were meta-analyzed using random-effects
      models, and sources of potential heterogeneity were examined through subgroup and
      sensitivity analyses. In addition, a comprehensive evaluation of potential dose
      response patterns was conducted. In the meta-analysis of all cohorts, a weakly
      elevated summary relative risk was observed (1.11, 95% CI: 1.03-1.19); however,
      statistically significant heterogeneity was present. In general, summary
      associations were attenuated (closer to the null and less heterogeneous) in
      models that isolated fresh red meat (from processed meat), adjusted for more
      relevant factors, analyzed women only, and were conducted in countries outside of
      the United States. Furthermore, no clear patterns of dose-response were apparent.
      In conclusion, the state of the epidemiologic science on red meat consumption and
      CRC is best described in terms of weak associations, heterogeneity, an inability
      to disentangle effects from other dietary and lifestyle factors, lack of a clear
      dose-response effect, and weakening evidence over time. KEY TEACHING POINTS: *The
      role of red meat consumption in colorectal cancer risk has been widely contested
      among the scientific community.*In the current meta-analysis of red meat intake
      and colorectal cancer, we comprehensively examined associations by creating
      numerous sub-group stratifications, conducting extensive sensitivity analyses,
      and evaluating dose-response using several different methods.*Overall, all
      summary associations were weak in magnitude with no clear dose-response
      patterns.*Interpretation of findings from epidemiologic studies investigating
      diet and health outcomes involves numerous methodological considerations, such as
      accurately measuring food intake, dietary pattern differences across populations,
      food definitions, outcome classifications, bias and confounding,
      multicollinearity, biological mechanisms, genetic variation in metabolizing
      enzymes, and differences in analytical metrics and statistical testing
      parameters.

PMID- 25941864
TI  - Martin H:son Holmdahl.

PMID- 25941865
TI  - Steric effects on the primary isotope dependence of secondary kinetic isotope
      effects in hydride transfer reactions in solution: caused by the isotopically
      different tunneling ready state conformations?
AB  - The observed 1 degrees  isotope effect on 2 degrees  KIEs in H-transfer reactions
      has recently been explained on the basis of a H-tunneling mechanism that uses the
      concept that the tunneling of a heavier isotope requires a shorter donor-acceptor
      distance (DAD) than that of a lighter isotope. The shorter DAD in D-tunneling, as
      compared to H-tunneling, could bring about significant spatial crowding effect
      that stiffens the 2 degrees  H/D vibrations, thus decreasing the 2 degrees  KIE.
      This leads to a new physical organic research direction that examines how
      structure affects the 1 degrees  isotope dependence of 2 degrees  KIEs and how
      this dependence provides information about the structure of the tunneling ready
      states (TRSs). The hypothesis is that H- and D-tunneling have TRS structures
      which have different DADs, and pronounced 1 degrees  isotope effect on 2 degrees 
      KIEs should be observed in tunneling systems that are sterically hindered. This
      paper investigates the hypothesis by determining the 1 degrees  isotope effect on
      alpha- and beta-2 degrees  KIEs for hydride transfer reactions from various
      hydride donors to different carbocationic hydride acceptors in solution. The
      systems were designed to include the interactions of the steric groups and the
      targeted 2 degrees  H/D's in the TRSs. The results substantiate our hypothesis,
      and they are not consistent with the traditional model of H-tunneling and 1
      degrees /2 degrees  H coupled motions that has been widely used to explain the 1
      degrees  isotope dependence of 2 degrees  KIEs in the enzyme-catalyzed H-transfer
      reactions. The behaviors of the 1 degrees  isotope dependence of 2 degrees  KIEs
      in solution are compared to those with alcohol dehydrogenases, and sources of the
      observed "puzzling" 2 degrees  KIE behaviors in these enzymes are discussed using
      the concept of the isotopically different TRS conformations. 

PMID- 25941866
TI  - Assessing sources of nitrate contamination in the Shiraz urban aquifer (Iran)
      using the delta(15)N and delta(18)O dual-isotope approach.
AB  - Nitrate ([Formula: see text]) is one of the major threats to the quality of the
      drinking water taken from the Shiraz aquifer. This aquifer undergoes high
      anthropogenic pressures from multiple local urban (including uncontrolled sewage
      systems), agricultural and industrial activities, resulting in [Formula: see
      text] concentrations as high as 149 mg L(-1), well above the 50 mg L(-1)
      guideline defined by the World Health Organisation. We coupled here classical
      chemical and dual isotope (delta(15)N and delta(18)O of [Formula: see text])
      approaches trying to characterize sources and potential processes controlling the
      budget of this pollutant. Chemical data indicate that nitrate in this aquifer is
      explained by distinct end-members: while mineral fertilizers isotopically show to
      have no impact, our isotope approach identifies natural soil nitrification and
      organic [Formula: see text] (manure and/or septic waste) as the two main
      contributors. Isotope data suggest that natural denitrification may occur within
      the aquifer, but this conclusion is not supported by the study of other chemical
      parameters. 

PMID- 25941867
TI  - The effects of noise vocoding on gap detection thresholds.
AB  - Gap detection threshold (GDT), the shortest silent interval a person can
      perceive, is a commonly used measure of temporal processing resolution. The
      purposes of this study were: (1) to examine the effects of noise vocoding, which
      has been used to simulate what signals sound like through a cochlear implant, on
      GDTs in normal-hearing subjects, and (2) to further the understanding of neural
      mechanisms underlying gap detection using the Auditory Late Response (ALR).
      Thirteen normal listeners participated. In behavioral tests, the GDTs were
      determined for the original and vocoded stimuli. In ALR recordings, the subjects
      were presented with auditory stimuli with and without containing gaps and stimuli
      with and without being vocoded. Results showed that GDTs were significantly
      elevated for vocoded stimuli with spectral resolutions of 4 and 20 channels
      compared to those for the original stimuli. A gap effect was observed in the post
      gap ALR. Current densities for N1 peaks evoked by stimuli with zero- vs. non-zero
      ms gaps, pre- vs. post-gap markers, and original vs. vocoded stimuli were
      obtained using the standardized low-resolution brain electromagnetic tomography
      (sLORETA) method. Paired comparisons of pre- and post-gap current density values
      were made. Results showed a statistical difference between the N1s evoked by pre-
      vs. post-gap markers, with the activation in the middle frontal gyrus and
      precentral gyrus. The results suggest that: (1) noise vocoding does affect
      temporal processing resolution assessed with GDTs, (2) gap detection may involve
      the recruitment of cognitive neural resources, and (3) the ALR has a potential
      value of objectively estimating temporal processing resolution. 

PMID- 25941869
TI  - Anti-genotoxic effect of naringin against bleomycin-induced genomic damage in
      human lymphocytes in vitro.
AB  - Naringin is a flavonoid found in grapefruit and other citrus fruits that shows
      antioxidant activity. The aim of the present study was to determine the anti
      genotoxic and protective effects of naringin on the chemotherapeutic/radiomimetic
      agent bleomycin (BLM) in human blood lymphocyte cultures in vitro using
      micronucleus test and chromosomal aberrations (CA) assay. We tested the three
      doses of naringin (1, 2, 3 ug/mL) and a single dose of BLM (20 ug/mL). BLM
      significantly increased the total CAs and micronucleus frequency at a
      concentration of 20 ug/mL. Naringin did not show any toxicity in doses of 1, 2,
      and 3 ug/mL. Combined treatments of BLM and naringin (2 and 3 ug/mL)
      significantly reduced micronucleus formation. Naringin dose-dependently decreased
      the total chromosome aberrations frequency induced by BLM. These results indicate
      that naringin could prevent BLM (20 ug/mL)-induced genotoxicity. 

PMID- 25941868
TI  - Social reward shapes attentional biases.
AB  - Paying attention to stimuli that predict a reward outcome is important for an
      organism to survive and thrive. When visual stimuli are associated with tangible,
      extrinsic rewards such as money or food, these stimuli acquire high attentional
      priority and come to automatically capture attention. In humans and other
      primates, however, many behaviors are not motivated directly by such extrinsic
      rewards, but rather by the social feedback that results from performing those
      behaviors. In the present study, I examine whether positive social feedback can
      similarly influence attentional bias. The results show that stimuli previously
      associated with a high probability of positive social feedback elicit value
      driven attentional capture, much like stimuli associated with extrinsic rewards.
      Unlike with extrinsic rewards, however, such stimuli also influence task-specific
      motivation. My findings offer a potential mechanism by which social reward shapes
      the information that we prioritize when perceiving the world around us.

PMID- 25941870
TI  - Rich Club Organization and Cognitive Performance in Healthy Older Participants.
AB  - The human brain is a complex network that has been noted to contain a group of
      densely interconnected hub regions. With a putative "rich club" of hubs
      hypothesized to play a central role in global integrative brain functioning, we
      assessed whether hub and rich club organizations are associated with cognitive
      performance in healthy participants and whether the rich club might be
      differentially involved in cognitive functions with a heavier dependence on
      global integration. A group of 30 relatively older participants (range = 39-79
      years of age) underwent extensive neuropsychological testing, combined with
      diffusion-weighted magnetic resonance imaging to reconstruct individual
      structural brain networks. Rich club connectivity was found to be associated with
      general cognitive performance. More specifically, assessing the relationship
      between the rich club and performance in two specific cognitive domains, we found
      rich club connectivity to be differentially associated with attention/executive
      functions-known to rely on the integration of distributed brain areas-rather than
      with visuospatial/visuoperceptual functions, which have a more constrained
      neuroanatomical substrate. Our findings thus provide first empirical evidence of
      a relevant role played by the rich club in cognitive processes. 

PMID- 25941871
TI  - Increased Stimulus Expectancy Triggers Low-frequency Phase Reset during
      Restricted Vigilance.
AB  - Temporal cues can be used to selectively attend to relevant information during
      abundant sensory stimulation. However, such cues differ vastly in the accuracy of
      their temporal estimates, ranging from very predictable to very unpredictable.
      When cues are strongly predictable, attention may facilitate selective processing
      by aligning relevant incoming information to high neuronal excitability phases of
      ongoing low-frequency oscillations. However, top-down effects on ongoing
      oscillations when temporal cues have some predictability, but also contain
      temporal uncertainties, are unknown. Here, we experimentally created such a
      situation of mixed predictability and uncertainty: A target could occur within a
      limited time window after cue but was always unpredictable in exact timing.
      Crucially to assess top-down effects in such a mixed situation, we manipulated
      target probability. High target likelihood, compared with low likelihood,
      enhanced delta oscillations more strongly as measured by evoked power and
      intertrial coherence. Moreover, delta phase modulated detection rates for
      probable targets. The delta frequency range corresponds with half-a-period to the
      target occurrence window and therefore suggests that low-frequency phase reset is
      engaged to produce a long window of high excitability when event timing is
      uncertain within a restricted temporal window. 

PMID- 25941872
TI  - Stable Task Representations under Attentional Load Revealed with Multivariate
      Pattern Analysis of Human Brain Activity.
AB  - Performing multiple tasks concurrently places a load on limited attentional
      resources and results in disrupted task performance. Although human neuroimaging
      studies have investigated the neural correlates of attentional load, how
      attentional load affects task processing is poorly understood. Here, task-related
      neural activity was investigated using fMRI with conventional univariate analysis
      and multivariate pattern analysis (MVPA) while participants performed blocks of
      prosaccades and antisaccades, either with or without a rapid serial visual
      presentation (RSVP) task. Performing prosaccades and antisaccades with RSVP
      increased error rates and RTs, decreased mean activation in frontoparietal brain
      areas associated with oculomotor control, and eliminated differences in
      activation between prosaccades and antisaccades. However, task identity could be
      decoded from spatial patterns of activation both in the absence and presence of
      an attentional load. Furthermore, in the FEFs and intraparietal sulcus, these
      spatial representations were found to be similar using cross-trial-type MVPA,
      which suggests stability under attentional load. These results demonstrate that
      attentional load may disrupt the strength of task-related neural activity, rather
      than the identity of task representations. 

PMID- 25941873
TI  - Cancer incidence in people living with HIV/AIDS in Israel, 1981-2010.
AB  - Antiretroviral therapy (ART) improved the survival of people living with HIV/AIDS
      (PLWHA) and decreased HIV-related morbidities. This study assesses the cancer
      incidence of all adult PLWHA in Israel by transmission routes before and after
      1996. This cohort study was based on cross-matching the National HIV/AIDS and
      Cancer Registries of all HIV/AIDS and cancer cases reported from 1981 to 2010
      with the National civil census. PLWHA were followed-up until cancer diagnosis,
      death, leaving Israel, or 2010, whichever occurred first. Cancer incidence was
      adjusted for age, and compared with the National incidence. Of all 5,154 PLWHA
      followed-up for 36,296 person-years, 362 (7.0%) developed cancer (997.4 cases per
      100,000 person-years). Higher hazard ratios to develop cancer were demonstrated
      among older PLWHA, Jewish people, and intravenous drug users. Cancer incidence
      among PLWHA was higher in the pre-ART period than after 1997 (1,232.0 and 846.7
      cases per 100,000 person-years, respectively). The incidence of AIDS-defining
      cancers was higher than non-AIDS-defining malignancies, and higher in the pre-ART
      than the post-ART period (777.0 and 467.2 cases per 100,000 person-years,
      respectively), while the incidence of non-AIDS-defining cancers showed the
      opposite trend (376.5 and 455.0 cases per 100,000 person-years, respectively).
      The incidence of AIDS-defining and non-AIDS-defining cancers declined between the
      pre-ART and the post-ART period by 2.0 to 3.4 times. PLWHA had higher rates of
      malignancies than the general population. In conclusion, cancer incidence among
      PLWHA was associated with age, and declined after ART introduction; yet it was
      higher than that of the general population. PLWHA may benefit from age-related
      cancer screening, increased adherence to ART, and reduction of environmental
      oncogenes. 

PMID- 25941874
TI  - Male Veteran Intimate Partner Violence (IPV) Program Outcomes.
AB  - The prominence and incidence of intimate partner violence (IPV) with male
      military veterans vary, but generally there is consensus that screening and
      intervention does help reduce IPV. Intervention is generally provided in the
      community via Batterer Intervention Programs. However, at the Department of
      Veterans Affairs (VA) intervention is provided via the Domestic Relations Clinic.
      Nationally the VA has limited treatment for male IPV. An aggregate sample (n =
      178) of participants was assessed using the Domestic Violence/Abuse Screen to
      measure covariate pre-test and post-test outcomes, program failure, and
      recidivism. The treatment approach is psycho-educationally based to meet the
      challenging and unique needs of the military veteran population. The results
      contribute to a more comprehensive understanding of IPV and highlight the need
      for more intervention and prevention approaches.

PMID- 25941876
TI  - Israel's Long-Term Care Social Insurance Scheme After a Quarter of a Century.
AB  - Long-term care social insurance schemes exist in a number of countries, while the
      introduction of such schemes enjoys some support in others. Israel's long-term
      care social insurance scheme has been operating since 1988. This article examines
      the emergence, goals, design, and impacts of this scheme and draws out some of
      the lessons that can be learned from Israel's quarter century experience of long
      term care social insurance. 

PMID- 25941875
TI  - Nonphotosynthetic pigments as potential biosignatures.
AB  - Previous work on possible surface reflectance biosignatures for Earth-like
      planets has typically focused on analogues to spectral features produced by
      photosynthetic organisms on Earth, such as the vegetation red edge. Although
      oxygenic photosynthesis, facilitated by pigments evolved to capture photons, is
      the dominant metabolism on our planet, pigmentation has evolved for multiple
      purposes to adapt organisms to their environment. We present an interdisciplinary
      study of the diversity and detectability of nonphotosynthetic pigments as
      biosignatures, which includes a description of environments that host
      nonphotosynthetic biologically pigmented surfaces, and a lab-based experimental
      analysis of the spectral and broadband color diversity of pigmented organisms on
      Earth. We test the utility of broadband color to distinguish between Earth-like
      planets with significant coverage of nonphotosynthetic pigments and those with
      photosynthetic or nonbiological surfaces, using both 1-D and 3-D spectral models.
      We demonstrate that, given sufficient surface coverage, nonphotosynthetic
      pigments could significantly impact the disk-averaged spectrum of a planet.
      However, we find that due to the possible diversity of organisms and
      environments, and the confounding effects of the atmosphere and clouds,
      determination of substantial coverage by biologically produced pigments would be
      difficult with broadband colors alone and would likely require spectrally
      resolved data.

PMID- 25941877
TI  - Determination of the potential illegal addition of beta-blockers to function
      foods by QuEChERS sample preparation and UPLC-MS/MS analysis.
AB  - A novel method was established for the determination of 11 beta-blockers in
      sedative functional foods using QuEchERS sample preparation coupled with UPLC
      MS/MS. The analytes were extracted twice with acetic acid-acetonitrile-methanol
      (0.1:3:7, v/v/v), and the extracts were purified with mixed QuEchERS adsorbents.
      Separation was performed on a C18 column, and detection using electrospray
      ionisation in positive-ion mode. The linear range for the 11 analytes was from 1
      to 500 MUg l(-1), and the correlation coefficients were above 0.9990. The limits
      of detection and quantification were 0.02-0.16 and 0.07-0.54 MUg kg(-1),
      respectively. The average recovery for 11 analytes at the three spiking levels
      varied from 71.8% to 121.9%, and the relative standard deviation was 2.4-12.6%.
      The method was applied to the analysis of beta-blockers in 22 real samples, but
      none of the analytes was detected. The proposed method is sensitive, efficient,
      reliable and applicable to real samples.

PMID- 25941878
TI  - Utrophin suppresses low frequency oscillations and coupled gating of
      mechanosensitive ion channels in dystrophic skeletal muscle.
AB  - An absence of utrophin in muscle from mdx mice prolongs the open time of single
      mechanosensitive channels. On a time scale much longer than the duration of
      individual channel activations, genetic depletion of utrophin produces low
      frequency oscillations of channel open probability. Oscillatory channel opening
      occurred in the dystrophin/utrophin mutants, but was absent in wild-type and mdx
      fibers. By contrast, small conductance channels showed random gating behavior
      when present in the same patch. Applying a negative pressure to a patch on a DKO
      fiber produced a burst of mode II activity, but channels subsequently closed and
      remained silent for tens of seconds during the maintained pressure stimulus. In
      addition, simultaneous opening of multiple MS channels could be frequently
      observed in recordings from patches on DKO fibers, but only rarely in wild-type
      and mdx muscle. A model which accounts for the single-channel data is proposed in
      which utrophin acts as gating spring which maintains the mechanical stability a
      caveolar-like compartment. The state of this compartment is suggested to be
      dynamic; its continuity with the extracellular surface varying over seconds to
      minutes. Loss of the mechanical stability of this compartment contributes to
      pathogenic Ca(2+) entry through MS channels in Duchenne dystrophy. 

PMID- 25941879
TI  - Acute painful diabetic neuropathy: an uncommon, remittent type of acute distal
      small fibre neuropathy.
AB  - INTRODUCTION: Acute painful diabetic neuropathy (APDN) is a distinctive diabetic
      polyneuropathy and consists of two subtypes: treatment-induced neuropathy (TIN)
      and diabetic neuropathic cachexia (DNC). The characteristics of APDN are (1.) the
      small-fibre involvement, (2.) occurrence paradoxically after short-term
      achievement of good glycaemia control, (3.) intense pain sensation and (4.)
      eventual recovery. In the face of current recommendations to achieve quickly
      glycaemic targets, it appears necessary to recognise and understand this
      neuropathy. METHODS AND RESULTS: Over 2009 to 2012, we reported four cases of
      APDN. Four patients (three males and one female) were identified and had a mean
      age at onset of TIN of 47.7 years (+/-6.99 years). Mean baseline HbA1c was 14.2%
      (+/-1.42) and 7.0% (+/-3.60) after treatment. Mean estimated time to correct
      HbA1c was 4.5 months (+/-3.82 months). Three patients presented with a mean time
      to symptom resolution of 12.7 months (+/-1.15 months). One patient had an initial
      normal electroneuromyogram (ENMG) despite the presence of neuropathic symptoms,
      and a second abnormal ENMG showing axonal and myelin neuropathy. One patient had
      a peroneal nerve biopsy showing loss of large myelinated fibres as well as
      unmyelinated fibres, and signs of microangiopathy. CONCLUSIONS: According to the
      current recommendations of promptly achieving glycaemic targets, it appears
      necessary to recognise and understand this neuropathy. Based on our observations
      and data from the literature we propose an algorithmic approach for differential
      diagnosis and therapeutic management of APDN patients.

PMID- 25941880
TI  - Correction to Atom Exchange between Aqueous Fe(II) and Structural Fe in Clay
      Minerals.

PMID- 25941881
TI  - In situ construction of three anion-dependent cu(i) coordination networks as
      promising heterogeneous catalysts for azide-alkyne "click" reactions.
AB  - Three Cu(I) coordination networks, namely, {[Cu2(bpz)2(CN)X].CH3CN}n, (X = Cl, 1;
      I, 3), {[Cu6(bpz)6(CH3CN)3(CN)3Br].2OH.14CH3CN}n, (2, bpz = 3,3',5,5'-tetramethyl
      4,4'-bipyrazole), were prepared by using solvothermal method. The cyanide ligands
      in these networks were generated in situ by cleavage of C-C bond of MeCN under
      solvothermal condition. The structures of these networks are dependent on halogen
      anions. Complex 1 is a ladderlike structure with MU2-CN(-) as rung and MU2-bpz as
      armrest. The Cl(-) in 1 is at terminal position but does not extend the one
      dimensional (1D) ladder to higher dimensionalities. Complex 2 is a three
      dimensional (3D) framework comprised of novel planar [Cu3Br] triangle and single
      Cu nodes, which are extended by MU2-bpz and MU2-CN(-) to form a novel (3,9)
      connected gfy network. Density functional theory calculations showed that single
      electron delocalization of Br atom induces the plane structure of [Cu3Br].
      Complex 3 also possesses a similar ladderlike subunit as in 1, but the I(-) acts
      as bidentate bridge to extend the ladder to 3D framework with a four-connected
      sra topology. The three networks show notable catalytic activity on the click
      reaction. The compared catalytic results demonstrate that complex 2 possesses the
      best catalysis performance among three complexes, which is ascribed to the
      largest solvent-accessible void (porosity: 2 (29.4%) > 1 (25.7%) > 3 (17.6%)) and
      the more Cu(I) active sites in 2. The present combined structure-property studies
      provide not only a new synthetic route to obtain a new kind of catalyst for click
      reaction but also the new insights on catalyst structure-function relationships. 

PMID- 25941882
TI  - Pulmonary Delivery of Voriconazole Loaded Nanoparticles Providing a Prolonged
      Drug Level in Lungs: A Promise for Treating Fungal Infection.
AB  - Current therapies are insufficient to prevent recurrent fungal infection
      especially in the lower part of the lung. A careful and systematic understanding
      of the properties of nanoparticles plays a significant role in the design,
      development, optimization, and in vivo performances of the nanoparticles. In the
      present study, PLGA nanoparticles containing the antifungal drug voriconazole was
      prepared and two best formulations were selected for further characterization and
      in vivo studies. The nanoparticles and the free drug were radiolabeled with
      technetium-99m with 90% labeling efficiency, and the radiolabeled particles were
      administered to investigate the effect on their blood clearance, biodistribution,
      and in vivo gamma imaging. In vivo deposition of the drug in the lobes of the
      lung was studied by LC-MS/MS study. The particles were found to be spherical and
      had an average hydrodynamic diameter of 300 nm with a smooth surface. The
      radiolabeled particles and the free drug were found to accumulate in various
      major organs. Drug accumulation was more pronounced in the lung in the case of
      administration of the nanoparticles than that of the free drug. The free drug was
      found to be excreted more rapidly than the nanoparticle containing drug following
      the inhalation route as assessed by gamma scintigraphy study. Thus, the study
      reveals that pulmonary administration of nanoparticles containing voriconazole
      could be a better therapeutic choice even as compared to the iv route of
      administration of the free drug and/or the drug loaded nanoparticles. 

PMID- 25941883
TI  - Antiviral Activity of Trichilia catigua Bark Extracts for Herpesvirus and
      Poliovirus.
AB  - Herpesvirus and poliovirus are responsible for important diseases in human and
      animal. Trichilia catigua a Brazilian native plant known as catigua has several
      medicinal properties among them antimicrobial for bacteria and protozoa, however,
      no antiviral activity has been reported yet. This study evaluated the antiviral
      activity of the crude extract (CE) and aqueous and ethyl acetate fractions (AF,
      EAF) obtained from T. catigua in the replication of the Herpes simplex virus (HSV
      1), bovine herpesvirus (BoHV-1) and poliovirus (PV-1). The cytotoxicity was
      analyzed by MTT assay and the antiviral effect was determined by the addition of
      extracts (0.25 to 100.0 MUg/ml), before (-2h and -1h), during (Oh) and after (1h
      and 2h) the viral infection, by plaque reduction assay, in HEp-2 cell culture.
      The virucidal activity and inhibition of viral adsorption were also evaluated. In
      addition, the combination index (CI) with Acyclovir (ACV - reference drug) was
      determined for HSV-1. CE, AF and EAF showed a low toxicity (CC(50) >400 ug/ml)
      and low inhibitory concentration (IC50), ranging from 2.44-34.25 ug/ml for
      herpesvirus and 0.67 to 1.8 ug/ml for PV-1, associated with high selectivity
      index. The tested compounds showed high virucidal effect and high ability to
      inhibit viral adsorption, for all virus. The CI demonstrated a synergic effect
      (CI<1) for AF and EAF comparatively to acyclovir (ACV). Our study demonstrated
      that the extract and fractions of T. catigua is promising for future antiviral
      drug design with economically feasible production.

PMID- 25941884
TI  - Bispecific antibodies: an innovative arsenal to hunt, grab and destroy cancer
      cells.
AB  - Targeted cellular immunotherapy with bifunctional antibodies (bsAbs) has emerged
      as a promising therapeutic approach for cancer over the last two decades.
      Progress in antibody engineering has led to the generation of many different
      types of antibody-derived entities that display at least two binding
      specificities. Most bsAbs consist of large IgG-like proteins with multiple
      antigen-binding regions containing Fc parts or smaller entities without Fc. BsAbs
      have the potential to engage effector cells of the immune system, thereby
      overcoming some of the immune response escape mechanisms of tumor cells.
      Preclinical and clinical trials of various bsAb constructs have demonstrated
      impressive results in terms of immune effector cell retargeting and induction of
      efficient anti-tumor responses. This review provides an overview of the
      established bsAbs focusing on improvements in format and design as well as the
      mechanisms of action of the most promising candidates and describes the results
      of the most recent clinical studies. 

PMID- 25941885
TI  - Preventing the spread of Alzheimer's disease neuropathology: a role for
      calcilytics?
AB  - The "amyloid cascade hypothesis" posits that an extracellular build-up of amyloid
      beta oligomers (Abeta-os) and polymers (fibrils) subsequently inducing toxic
      hyperphosphorylated (p)-Tau oligomers (p-Tau-os) and neurofibrillary tangles
      starts the sporadic late-onset Alzheimer's disease (LOAD) in the aged lateral
      entorhinal cortex. Conversely, mutated genes cause a diffuse cerebral
      Abetas/Abeta-os overproduction promoting early-onset familiar AD (EOFAD). Surplus
      exogenous Abeta-os exert toxic actions at several levels. They reach the nuclei
      of human astrocyte-neurons teams (ANTs) to enhance the transcription of Abeta
      precursor protein (APP) and beta-secretase/BACE1 genes. The overexpressed APP and
      BACE1 proteins act in concert with gamma-secretase to overproduce endogenous
      Abetas/Abeta-os, of which a few enter the nuclei to upkeep Abetas overproduction,
      while the rest gather in the cytoplasm, damage mitochondria, and are
      oversecreted. Simultaneously, extracellular Abeta-os bind the ANTs' calcium
      sensing receptors (CaSRs) activating signalings that hinder the proteolysis and
      hence favor the surplus hoarding/secretion of Abetas/Abeta-os. Overreleased Abeta
      os spread, reach growing numbers of adjacent ANTs to recruit them to
      overproduce/oversecrete further Abeta-os amounts via the just mentioned
      mechanisms. Alongside, Abeta*CaSR signalings elicit a noxious
      overproduction/overrelease of nitric oxide (NO) and vascular endothelial growth
      factor (VEGF)-A from ANTs' astrocytes. While astrocytes survive the toxic
      onslaught, neurons die. Thus, AD progression is driven by ceaselessly self
      sustaining neurotoxic cycles, which engender first Abeta-os and later p-Tau-os
      that cooperatively destroy increasingly wider cognition-related cortical areas.
      Notably, a highly selective allosteric CaSR antagonist (calcilytic), like NPS
      2143, does preserve human cortical postnatal HCN-1A neurons viability
      notwithstanding the presence of exogenous Abeta-os by suppressing the otherwise
      elicited oversecretion and spread of newly synthesized Abeta-os. Therefore, if
      given at minimal cognitive impairment or earlier stages, calcilytics could halt
      AD progression and preserve the patients' cortical neurons, cognitive abilities,
      and eventually life. 

PMID- 25941886
TI  - Nasal Vaccines Against Hepatitis B: An Update.
AB  - After several decades of immunization against hepatitis B virus, the question
      still remains whether a new vaccine could avoid the limitations of the current
      vaccine similar to those associated with its injectable form or ineffectiveness
      on chronic hepatitis B disease. A hypothesis to overcome first limitation is the
      development of an intranasal vaccine, self-administered, able to achieve not only
      systemic immunity, but also sIgA on the vaginal mucosa which would be a great
      advantage to prevent the sexually transmitted disease cases. Injectable hepatitis
      B vaccines that are already available in the market led to achieving protection
      mainly through a strong antibody-mediated response. For chronic hepatitis, a
      strong cellular immune response would also be required. The aim of this review is
      to give an overview of the work done in recent years, with the objective of
      developing a vaccine that can be administered by intranasal route. A discussion
      of the leading studies is presented, focusing not only on potential antigens, but
      also on promising adjuvants for the hepatitis B antigen. The results of the
      immune response generated with different formulations are summarized in tables.
      It is important to note that almost all studies claimed the induction of specific
      mucosal immune response (sIgA) and a balanced cellular and humoral Th1/Th2 or a
      Th1-type immune response. The further evaluation of these formulations, using a
      laboratory animal model of viral hepatitis B, would allow scientific community to
      conclude about the utility of these new adjuvants, particularly on a combined
      immunotherapy strategy for chronic hepatitis B. 

PMID- 25941888
TI  - Quercetin Potently Reduces Biofilm Formation of the Strain Pseudomonas aeruginosa
      PAO1 in vitro.
AB  - This work was focused on in vitro evaluation of anti-biofilm and anti-quorum
      sensing effects of four selected flavonoid compounds /(+)-catechin, caffeic acid,
      quercetin and morin/ using the strain Pseudomonas aeruginosa PAO1. At a
      concentration of 0.5 MIC quercetin was the only compound found to potently reduce
      both P. aeruginosa biofilm formation (95%) and its twitching motility. The
      chemical scaffold of quercetin, a common dietary polyphenol, may actually inspire
      development of novel and more effective medicinal agents targeting P. aeruginosa,
      the bacterium well known for its resistance. 

PMID- 25941889
TI  - Simultaneous detection of pathogenic bacteria using agglutination test based on
      colored silica nanoparticles.
AB  - Aimed to explore an agglutination test which can simultaneously detect two
      pathogenic bacteria, an agglutination test based on colored silica nanoparticles
      (colored-SiNps) was established in this work. Monodisperse colored-SiNps were
      used as agglutination test carriers; red-SiNps and blue-SiNps were prepared by
      reverse microemulsion with C.I. Reactive red 136 and C.I. Reactive Blue 14. Then
      the red-SiNps were sensitized with antibodies against E. sakazaki and denoted as
      IgG-red-SiNps; The blue-SiNps were coated with antibodies against S. pullorum and
      S. Gallinarum and denoted as IgGblue- SiNps. The mixture solution of IgG-red
      SiNps and IgG-blue-SiNps could simultaneously agglutinate with E. sakazakii and
      S. pullorum and S. gallinarum on glass slide. The E. sakazakii and S. pullorum
      and S. gallinarum could be simultaneously detected by agglutination test with
      obvious agglutination phenomena. The E. sakazakii and S. pullorum and S.
      gallinarum could both be detected in a range from 4*10(3) to 4*10(9) CFU/mL. The
      pullorum and S. gallinarum and E. sakazakii in the infected food sample were
      detected by mixture solution of IgG-red-SiNps and IgG-blue-SiNps too. This
      agglutination test was easy and rapid, it might be useful for in situ rapid
      detection method for simultaneously screening different pathogenic microorganisms
      of foods and feeds in the field. 

PMID- 25941887
TI  - Scalable downstream strategies for purification of recombinant adeno- associated
      virus vectors in light of the properties.
AB  - Recombinant adeno-associated virus (rAAV) vector is one of the promising delivery
      tools for gene therapy. Currently, hundreds of clinical trials are performed but
      the major barrier for clinical application is the absence of any ideal large
      scale production technique to obtain sufficient and highly pure rAAV vector. The
      large scale production technique includes upstream and downstream processing. The
      upstream processing is a vector package step and the downstream processing is a
      vector purification step. For large scale downstream processing, the scientists
      need to recover rAAV from dozens of liters of cell lysate or medium, and a
      variety of purification strategies have been developed but not comprehensively
      compared till now. Consequently, this review will evaluate the scalable
      downstream purification strategies systematically, especially those based on the
      physicochemical properties of AAV virus, and attempt to find better scalable
      downstream strategies for rAAV vectors. 

PMID- 25941892
TI  -    Paget's Disease of the Breast Mimicking a Chronic Wound .
AB  - Paget's disease of the breast is a rare malignancy of the nipple-areola complex
      and accounts for 1%-4% of all breast cancers. The disease is frequently
      associated with an underlying in-situ or invasive carcinoma in the breast tissue
      that extends to the nipple and areola. Paget's disease is characterized
      clinically by eczema-like inflammatory skin changes and histologically by
      malignant cell infiltration in the dermis (Paget's cells). Although Paget's
      presents less commonly than a palpable mass or mammography abnormality, it is an
      important consideration in the differential diagnosis of a persisting nipple
      areola abnormality. Diagnosis may be delayed by several months or even years
      because of Paget's seemingly benign appearance. The following case demonstrates
      this particular situation. Biopsy of a chronic wound that shows no evidence of
      healing over time is of paramount importance, especially in the case of a chronic
      breast lesion. 

PMID- 25941890
TI  - Triglyceride-Lowering Response to Plant Sterol and Stanol Consumption.
AB  - Phytosterols (PS) have long been recognized for their cholesterol-lowering
      action, however, recent work has highlighted triglyceride (TG)-lowering responses
      to PS that may have been overlooked in previous human interventions and
      mechanistic animal model studies. This review assesses the current state of
      knowledge regarding the effect of dietary PS supplementation on blood TG
      concentrations by examining the average therapeutic response, potential
      mechanisms, and metabolic and genetic factors that may contribute to inter
      individual variability. Data from human intervention trials demonstrates that,
      compared to baseline concentrations, PS supplementation results in a variable TG
      lowering response ranging from 0.8 to 28%. It is evident that
      hypertriglyceridemic individuals (>1.7 mmol/L) have a greater TG-lowering
      response to PS (11-28%) than subjects with normal plasma TG concentrations (0.8
      7%). Although a genetic basis for the variable TG-lowering effects of PS is
      probable, there are only limited studies to draw on. The available data suggest
      that polymorphisms in the apolipoprotein E (apoE) gene may affect responsiveness,
      with PS-induced reductions in TG more readily evident in apoE2 than apoE3 or E4
      subjects. Although only a minimal number of animal model studies have been
      conducted to specifically examine the mechanisms whereby PS may reduce blood TG
      concentrations, it appears that there may be multiple mechanisms involved
      including interruption of intestinal fatty acid absorption and modulation of
      hepatic lipogenesis and very low density lipoprotein packaging and secretion. In
      summary, the available data suggest that PS may be an effective therapy to lower
      blood TG, particularly in hypertriglyceridemic individuals. However, before PS
      can be widely recommended as a TG-lowering therapy, studies that are specifically
      powered and designed to fully access therapeutic responses and the mechanisms
      involved are required. 

PMID- 25941891
TI  - Organocatalytic asymmetric C-H vinylation and arylation of N-acyl
      tetrahydroisoquinolines.
AB  - The first organocatalytic enantioselective oxidative C-H functionalization of N
      acyl tetrahydroisoquinolines with vinyl and aryl boronates promoted by a chiral
      Bronsted acid is described. This metal-free process tolerates a wide range of
      electronically varied N-acyl tetrahydroisoquinolines and structurally diverse
      boronates with good to excellent enantioselectivities. 

PMID- 25941893
TI  - Unexpected wound effects of local arginine infusion: reduced granulation tissue
      formation and elevated homocysteine concentrations .
AB  - Background. Therapeutic use of supplemental arginine has been proposed as an
      efficacious method to produce nitric oxide (NO) from nitric oxide synthase (NOS)
      and proline and polyamines from arginase to improve wound healing. This study was
      designed to examine the effects of arginine on wound angiogenesis and granulation
      tissue formation. METHODS: A ventral hernia, surgically created in the abdominal
      wall of 12 swine, was repaired with silicone sheeting and skin closure. An
      osmotic infusion pump, inserted in a remote subcutaneous pocket, continuously
      delivered saline solution (n = 6) or L-arginine (n = 6) into the wound
      environment. Granulation tissue thickness was determined by ultrasonography.
      Fluid was aspirated serially from the developing wound compartment for
      measurement of nitrite/nitrate (NOx) and amino acid concentrations. On day 14,
      the animals were sacrificed, and the abdominal wall was harvested for histologic
      analysis. RESULTS: In animals that received saline, a 4-fold increase in
      granulation tissue thickness was measured during the 14-day interval. In
      contrast, in L-arginine treated animals, the day 14 granulation tissue thickness
      was unchanged from day 4 values of saline treated animals (10.1 mm +/- 1.1 mm
      versus 20.2 mm +/- 1.7 mm at day 14; P < 0.05). Wound vessel count and vascular
      surface area estimates derived from image analysis of histologic sections were 2-
      to 3-fold lower in L-arginine animals compared to controls (P < 0.05).
      Progressive and sustained increases in wound fluid NOx and homocysteine levels
      were noted in L-arginine treated animals compared to controls (230 um/L versus 75
      um/L at day 14 [P < 0.05]; peak 25.2 um/L versus 17.3 um/L at day 7 [P <0.05],
      respectively). CONCLUSION: Supplemental arginine induces sustained NO production
      and creates a methylation demand, resulting in elevated homocysteine
      concentrations with consequent reductions in wound angiogenesis and granulation
      tissue formation.    .

PMID- 25941894
TI  - The effects of topical and systemic Beta glucan administration on wound healing
      impaired by corticosteroids.
AB  - Background. Corticosteroid hormones are widely used to treat a variety of
      diseases. Corticosteriods have been shown to impair wound healing, which has
      become a serious clinical problem in wound care. The present study was designed
      to evaluate the efficacy of topical and systemic beta glucan administration on
      wound healing impaired by corticosteroids. METHODS: Wistar albino rats were used
      for the incision and excision wound models. Percentage of wound contraction,
      epithelialization period, hydroxyproline level, histopathological examination,
      and tensile strength were evaluated. RESULTS: Although both systemic and local
      administration of beta glucan enhanced percentage wound contraction, improved
      epithelialization time, tensile strength, and elevated hydroxyproline level,
      systemic administration was found to be more effective. CONCLUSION: These results
      indicate that systemic and topical beta glucan improve wound healing that has
      been impaired by corticosteroids, and that systemic administration is more
      effective than topical application.

PMID- 25941895
TI  -    A Review of Collagen and Collagen-based Wound Dressings.
AB  - Collagen is a key component of a healing wound. In this review, a general
      description of the wound healing process is provided focusing on collagen's
      unique role. The mode of action (MoA) of collagen-based dressings is also
      addressed. Due to a number of potential stimuli (local tissue ischemia,
      bioburden, necrotic tissue, repeated trauma, etc.), wounds can stall in the
      inflammatory phase contributing to the chronicity of the wound. One key component
      of chronic wounds is an elevated level of matrix metalloproteinases (MMPs). At
      elevated levels, MMPs not only degrade nonviable collagen but also viable
      collagen. In addition, fibroblasts in a chronic wound may not secrete tissue
      inhibitors of MMPs (TIMPs) at an adequate level to control the activity of MMPs.
      These events prevent the formation of the scaffold needed for cell migration and
      ultimately prevent the formation of the extracellular matrix (ECM) and
      granulation tissue. Collagen based wound dressings are uniquely suited to address
      the issue of elevated levels of MMPs by acting as a 'sacrificial substrate' in
      the wound. It has also been demonstrated that collagen breakdown products are
      chemotactic for a variety of cell types required for the formation of granulation
      tissue. In addition, collagen based dressings have the ability to absorb wound
      exudates and maintain a moist wound environment. 

PMID- 25941896
TI  - Efficiency of Therapeutic Ultrasound for Healing Venous Leg Ulcers in
      Surgically-treated Patients.
AB  - The aim of this study was to evaluate the efficiency of therapeutic ultrasound
      (US) for healing of venous leg ulcers in surgically treated patients. Study
      endpoints were the number of completely healed wounds and the clinical parameters
      predicting the outcome. Seventy patients with venous leg ulcers were included in
      this study, and ultimately allocated into two comparative groups. Group A
      consisted of 33 patients (21 women, 12 men). They were treated with the US,
      compression stockings, and drug therapy. Group B (control) consisted of 37
      patients (22 women, 15 men). They were treated with the compression stockings and
      drug therapy only, administered just as in group A. Ten patients in group A and
      12 in group B healed completely (P > 0.05). Comparison of Gilman Index and
      relative change of the total surface area, length, width, and volume did not
      demonstrate any difference (P > 0.05) between the groups. A more statistically
      efficient decrease of pus (P = 0.03) and greater promotion of granulation (P =
      0.03) were observed in group A compared to group B. However, the noted changes
      did not have an influence on acceleration of therapy or final stage of the wound
      healing process because no differences were detected in the epidermization rate
      of the ulcers in either group. There are no specific indications that US
      application promotes healing in patients after surgical operation. 

PMID- 25941897
TI  - Coherence Transfer by Passage Pulses in Electron Paramagnetic Resonance
      Spectroscopy.
AB  - Linear passage pulses provide a simple approach to ultra-wideband electron
      paramagnetic resonance (EPR) spectroscopy. We show by numerical simulations that
      the efficiency of inversion of polarization or coherence order on a single
      transition by idealized passage pulses is an exponential function of critical
      adiabaticity during passage, which allows for defining an effective flip angle
      for fast passage. This result is confirmed by experiments on E' centers in
      Herasil glass. Deviations from the exponential law arise due to relaxation and a
      distribution of the adiabaticity parameter that comes from inhomogeneity of the
      irradiation field. Such inhomogeneity effects as well as edge effects in finite
      sweep bands cause a distribution of dynamic phase shifts, which can be partially
      refocused in echo experiments. In multilevel systems, passage of several
      transitions leads to generation of coherence on formally forbidden transitions
      that can also be described by the concept of an effective flip angle. On the one
      hand, such transfer to coherence on forbidden transitions is a significant
      magnetization loss mechanism for dipole-dipole coupled electron spin pairs at
      distances below about 2 nm. On the other hand, it can potentially be harnessed
      for electron spin echo envelope modulation (ESEEM) experiments, where matching of
      the irradiation field strength to the nuclear Zeeman frequency leads to efficient
      generation of nuclear coherence and efficient back transfer to electron coherence
      on allowed transitions at high adiabaticity. 

PMID- 25941898
TI  - [Relationships between widespread pain and thresholds pain tolerance on tender
      points in Portuguese women with fibromyalgia: impact on daily life].
AB  - OBJECTIVES: to establish a relationship between widespread pain subjectively
      perceived and threshold pain tolerance on tender points, and to determine whether
      there are differences in threshold pain tolerance on tender points between the
      upper and lower body, as well as between the dominant and non-dominant side, and
      whether these differences have an impact on the daily life of Portuguese women
      with fibromyalgia (FM). MATERIAL & METHODS: thirty-one women with FM aged between
      34 and 67 years volunteered for the study. Threshold pain tolerance was assessed
      at critical points using a digital algometer pressure; the widespread pain index
      (WPI) was constructed by the addition of 19 painful body regions; and the impact
      on the daily life assessed by the Portuguese version of the Fibromyalgia Impact
      Questionnaire (FIQ), with individual interviews. RESULTS: significant differences
      between the percentage of threshold pain tolerance of the whole body and the
      scales of widespread pain subjectively perceived were observed, showing that the
      widespread pain subjectively perceived by patients was between +25.9% and +27.5%.
      Also, significant differences between threshold pain tolerance of tender points
      located on the upper and lower body (1.9 +/- 0.5 kg/cm2 vs. 2.6 +/- 0.7 kg/cm2;
      respectively) were observed. However, no significant differences were found
      between threshold pain tolerance of tender points located on dominant and non
      dominant sides (2.1 +/- 0.5 kg/cm2 e 2.1 +/- 0.6 kg/cm2; respectively).
      Additionally, the analysis showed significant correlations between pain and
      patient's daily life in: FIQ total score, physical function, feel good, job
      ability and fatigue. CONCLUSIONS: the women with FM show higher widespread pain
      subjectively perceived than threshold pain tolerance on tender points.
      Furthermore, the pain suffered by the patients with FM, especially that located
      on the upper body, either on the dominant or on the non-dominant side, has a
      negative influence on physical function, job ability, fatigue and feel good,
      affecting daily life.

PMID- 25941899
TI  - Transplantation of Adipose Tissue-Derived Mesenchymal Stem Cells Prevents the
      Development of Lupus Dermatitis.
AB  - MRL/lpr mice spontaneously develop high titers of anti-dsDNA antibodies and
      symptoms such as glomerular nephritis and organ weight gain. They also develop
      spontaneous skin inflammation similar to the cutaneous lesions common in human
      lupus erythematosus. This study aimed to compare the effects of long-term serial
      administration of human adipose tissue-derived mesenchymal stem cells (ASCs),
      CTLA4Ig-overexpressing ASCs, and cyclophosphamide treatment in MRL/lpr mice.
      MRL/lpr mice were divided into saline (C), cyclophosphamide (Y), ASC early (E),
      ASC late (L), and CTLA4Ig-overexpressing ASC (CT) treatment groups. Background
      matched control MRL/MPJ mice treated with saline (N) were also compared. The
      treatment period was 5-23 weeks, except for the L group (15-23 weeks). Blood and
      tissue samples were collected when the mice were 24 weeks old. Organ weight, anti
      dsDNA antibodies, urine protein, skin and kidney histologic abnormalities, and
      trabecular bone volume were evaluated. The Y group showed the greatest decrease
      in anti-dsDNA antibodies, organ weight, degree of kidney inflammation and
      glomerular infiltration of C3, and incidence rate of severe proteinuria; the E,
      L, and CT treatment groups showed better results than the C group. ASC
      transplantation reduced anti-dsDNA antibody levels significantly. Mice treated
      with ASCs or CTLA4Ig-ASCs starting from the early disease stage did not show
      dermatitis upon gross examination; they demonstrated significant improvement in
      hyperkeratosis, acanthosis, and inflammatory cell infiltration scores in
      histopathology. Micro-CT analysis revealed that cyclophosphamide treatment
      significantly decreased bone volume and increased bone spacing in the trabecular
      bone. Thus, we found that ASC and CTLA4-ASC treatments prevent lupus dermatitis
      development in MRL/lpr mice without adverse effects. 

PMID- 25941900
TI  - Single-molecule studies of acidity distributions in mesoporous aluminosilicate
      thin films.
AB  - Solid acid catalysts are important for many petrochemical processes. The ensemble
      methods most often employed to characterize acid site properties in catalyst
      materials provide limited insights into their heterogeneity. Single-molecule (SM)
      fluorescence spectroscopic methods provide a valuable route to probing the
      properties of individual microenvironments. In this work, dual-color SM methods
      are adopted to study acidity distributions in mesoporous aluminosilicate (Al-Si)
      films prepared by the sol-gel method. The highly fluorescent pH-sensitive dye C
      SNARF-1 was employed as a probe. The ratio of C-SNARF-1 emission in two bands
      centered at 580 and 640 nm provides an effective means to sense the pH of bulk
      solutions. In mesoporous thin films, SM emission data provide a measure of the
      effective pH of the microenvironment in which each molecule resides. SM emission
      data were obtained from mesoporous Al-Si films as a function of Al2O3 content for
      films ranging from 0% to 30% alumina. Histograms of the emission ratio reveal a
      broad distribution of acidity properties, with the film microenvironments
      becoming more acidic, on average, as the alumina content of the films increases.
      This work provides new insights into the distribution of Bronsted acidity in
      solid acids that cannot be obtained by conventional means. 

PMID- 25941901
TI  - Graphene/Cu nanoparticle hybrids fabricated by chemical vapor deposition as
      surface-enhanced Raman scattering substrate for label-free detection of
      adenosine.
AB  - We present a graphene/Cu nanoparticle hybrids (G/CuNPs) system as a surface
      enhanced Raman scattering (SERS) substrate for adenosine detection. The Cu
      nanoparticles wrapped by a monolayer graphene shell were directly synthesized on
      flat quartz by chemical vapor deposition in a mixture of methane and hydrogen.
      The G/CuNPs showed an excellent SERS enhancement activity for adenosine. The
      minimum detected concentration of the adenosine in serum was demonstrated as low
      as 5 nM, and the calibration curve showed a good linear response from 5 to 500
      nM. The capability of SERS detection of adenosine in real normal human urine
      samples based on G/CuNPs was also investigated and the characteristic peaks of
      adenosine were still recognizable. The reproducible and the ultrasensitive
      enhanced Raman signals could be due to the presence of an ultrathin graphene
      layer. The graphene shell was able to enrich and fix the adenosine molecules,
      which could also efficiently maintain chemical and optical stability of G/CuNPs.
      Based on the G/CuNPs system, the ultrasensitive SERS detection of adenosine in
      varied matrices was expected for the practical applications in medicine and
      biotechnology. 

PMID- 25941902
TI  - gamma-Glutamylcyclotransferase Knockdown Inhibits Growth of Lung Cancer Cells
      Through G0/G1 Phase Arrest.
AB  - Lung cancer as an aggressive type tumor is rapidly growing and has become the
      leading cause of cancer-related death worldwide. gamma-Glutamylcyclotransferase
      (GGCT) has been shown as a diagnostic marker in various cancers. To reveal
      whether there is a correlation between GGCT and lung cancer, GGCT expression in
      human lung cancer cell lines was first determined by real-time quantitative PCR
      and western blot. GGCT is expressed in all tested lung cancer cell lines, A549,
      H1299, and H460. Then, a lentivirus-based system was applied to knock down GGCT
      in A549 cells, which were thus divided into Lv-shGGCT, Lv-shCon, and Con
      (noninfected) groups. Methylthiazol tetrazolium assay showed that the cell
      proliferation was decreased by over 50% in the Lv-shGGCT group compared with
      controls. The size and number of colonies were dramatically reduced in the GGCT
      knockdown group, as measured by colony formation assay. Moreover, A549 cells
      infected with Lv-shGGCT were arrested in the G0/G1 phase as assayed by flow
      cytometry. Furthermore, the expression levels of CDK4, CDK6, and cyclin D1 were
      decreased and the cleaved level of PARP was increased in GGCT knockdown cells. In
      conclusion, GGCT plays a critical role in lung cancer cell proliferation and may
      be a potential cancer therapeutic target. 

PMID- 25941903
TI  - Tetrahydro Iso-Alpha Acids and Hexahydro Iso-Alpha Acids from Hops Inhibit
      Proliferation of Human Hepatocarcinoma Cell Lines and Reduce Diethylnitrosamine
      Induced Liver Tumor Formation in Rats.
AB  - Chronic inflammation plays important role in the pathogenesis of hepatocellular
      carcinoma (HCC). To date, no antiinflammatory approach has shown its efficacy in
      preventing HCC occurrence in humans. Because tetra- and hexahydro isoalpha acids
      (THIAA and HHIAA) from hops elicit antiinflammatory properties, we evaluated
      these compounds for antitumor effects in vitro in human HCC cell lines (HepG2,
      Hep3B, Huh7) and in vivo in diethylnitrosamine (DEN)-induced animal model of HCC.
      In human HCC cell lines, THIAA and HHIAA reduced cell proliferation and viability
      which was associated with the inhibition of the NF-kappaB-DNA binding and tumor
      necrosis factor alpha mRNA expression. Both compounds also inhibited
      phosphorylation of the mTOR effector p70S6 kinase without affecting ERK, AKT,
      JNK, and GSK3beta phosphorylation or activator protein-1 activation. In DEN
      treated rats, administration of THIAA and HHIAA in food reduced the tumor numbers
      and the expression of the cellular transformation marker glutathione-S
      transferase in the liver. In conclusion, THIAA and HHIAA show antitumor
      properties in vitro in human HCC cell lines as well as in vivo in a chemically
      induced animal model of HCC. 

PMID- 25941904
TI  - Uranyl adsorption at solvated edge surfaces of 2 : 1 smectites. A density
      functional study.
AB  - We systematically studied the adsorption of uranyl(vi) on two common edge
      surfaces, (010) and (110), of 2 : 1 smectite clay minerals, using standard
      periodic DFT models. To describe various types of permanently charged clay
      minerals, we introduced charged defects into the initially neutral layer of
      pyrophyllite, cation substitutions in tetrahedral (beidellitic) and octahedral
      (montmorillonitic) sheets. Comparing uranyl(vi) species at various sites of these
      two types of surfaces, we found that structural parameters of such adsorption
      complexes are essentially determined by the surface chemical groups forming the
      adsorption site, not by the type of the clay mineral. Even for sites involving a
      substituted cation we noticed only a weak effect of the substitution on the
      geometric parameters. Geometry optimization resulted in adsorbed uranyl or uranyl
      hydroxide, with coordination numbers of 4 or 5. However, in most cases the same
      species was determined on the same type of site, independent of the
      substitutions. Optimization of adsorbed uranyl leads to hydrolysis at sites close
      to a AlOH(-1/2) surface group, resulting in uranyl monohydroxide as adsorbate and
      protonation of the AlOH(-1/2) group. While most species are equatorially five
      coordinated, coordination 4 is preferred when uranyl adsorbs on mixed AlO(H)
      SiO(H) sites. Calculated formation energies of surface complexes do not single
      out a preferred species or site, but point to an equilibrium of several species.
      Comparison to experiment and consideration of pH conditions suggests AlOHOH and
      AlOH-SiO sites of (010) surfaces and AlOmOH, SiOOm, and AlOH-SiO sites of (110)
      surfaces as most probable for uranyl adsorption. 

PMID- 25941905
TI  - Suspended, Shrinkage-Free, Electrospun PLGA Nanofibrous Scaffold for Skin Tissue
      Engineering.
AB  - Electrospinning is a technique for creating continuous nanofibrous networks that
      can architecturally be similar to the structure of extracellular matrix (ECM).
      However, the shrinkage of electrospun mats is unfavorable for the triggering of
      cell adhesion and further growth. In this work, electrospun PLGA nanofiber
      assemblies are utilized to create a scaffold. Aided by a polypropylene auxiliary
      supporter, the scaffold is able to maintain long-term integrity without
      dimensional shrinkage. This scaffold is also able to suspend in cell culture
      medium; hence, keratinocyte cells seeded on the scaffold are exposed to air as
      required in skin tissue engineering. Experiments also show that human skin
      keratinocytes can proliferate on the scaffold and infiltrate into the scaffold. 

PMID- 25941906
TI  - Characteristics of back corona discharge in a honeycomb catalyst and its
      application for treatment of volatile organic compounds.
AB  - The main technical challenges for the treatment of volatile organic compounds
      (VOCs) with plasma-assisted catalysis in industrial applications are large volume
      plasma generation under atmospheric pressure, byproduct control, and aerosol
      collection. To solve these problems, a back corona discharge (BCD) configuration
      has been designed to evenly generate nonthermal plasma in a honeycomb catalyst.
      Voltage-current curves, discharge images, and emission spectra have been used to
      characterize the plasma. Grade particle collection results and flow field
      visualization in the discharge zones show not only that the particles can be
      collected efficiently, but also that the pressure drop of the catalyst layer is
      relatively low. A three-stage plasma-assisted catalysis system, comprising a
      dielectric barrier discharge (DBD) stage, BCD stage, and catalyst stage, was
      built to evaluate toluene treatment performance by BCD. The ozone analysis
      results indicate that BCD enhances the ozone decomposition by collecting aerosols
      and protecting the Ag-Mn-O catalyst downstream from aerosol contamination. The GC
      and FTIR results show that BCD contributes to toluene removal, especially when
      the specific energy input is low, and the total removal efficiency reaches almost
      100%. Furthermore, this removal results in the emission of fewer byproducts. 

PMID- 25941907
TI  - To gel or not to gel: correlating molecular gelation with solvent parameters.
AB  - Rational design of small molecular gelators is an elusive and herculean task,
      despite the rapidly growing body of literature devoted to such gels over the past
      decade. The process of self-assembly, in molecular gels, is intricate and must
      balance parameters influencing solubility and those contrasting forces that
      govern epitaxial growth into axially symmetric elongated aggregates. Although the
      gelator-gelator interactions are of paramount importance in understanding
      gelation, the solvent-gelator specific (i.e., H-bonding) and nonspecific (dipole
      dipole, dipole-induced and instantaneous dipole induced forces) intermolecular
      interactions are equally important. Solvent properties mediate the self-assembly
      of molecular gelators into their self-assembled fibrillar networks. Herein,
      solubility parameters of solvents, ranging from partition coefficients (log P),
      to Henry's law constants (HLC), to solvatochromic parameters (ET(30)), and Kamlet
      Taft parameters (beta, alpha and pi), and to Hansen solubility parameters
      (deltap, deltad, deltah), are correlated with the gelation ability of numerous
      classes of molecular gelators. Advanced solvent clustering techniques have led to
      the development of a priori tools that can identify the solvents that will be
      gelled and not gelled by molecular gelators. These tools will greatly aid in the
      development of novel gelators without solely relying on serendipitous
      discoveries. These tools illustrate that the quest for the universal gelator
      should be left in the hands of Don Quixote and as researchers we must focus on
      identifying gelators capable of gelling classes of solvents as there is likely no
      one gelator capable of gelling all solvents. 

PMID- 25941908
TI  - 2-Vinyl Threoninol Derivatives via Acid-Catalyzed Allylic Substitution of
      Bisimidates.
AB  - A diastereoselective synthesis of 4-vinyl oxazolines syn-2 was developed based on
      an acid-catalyzed cyclization of bistrichloroacetimidates (E)-1. The reaction
      likely involves an allyl carbenium ion intermediate in which the adjacent
      stereocenter directs the stereoselectivity for C-N bond formation. Oxazolines syn
      2 were transformed to C-quaternary threoninol, threoninal, and threonine
      derivatives which can be further incorporated into complex natural compounds. 

PMID- 25941909
TI  - A surface EMG test tool to measure proportional prosthetic control.
AB  - In upper limb amputees, prosthetic control training is recommended before and
      after fitting. During rehabilitation, the focus is on selective proportional
      control signals. For functional monitoring, many different tests are available.
      None can be used in the early phase of training. However, an early assessment is
      needed to judge if a patient has the potential to control a certain prosthetic
      set-up. This early analysis will determine if further training is needed or if
      other strategies would be more appropriate. Presented here is a tool that is
      capable of predicting achievable function in voluntary EMG control. This tool is
      applicable to individual muscle groups to support preparation of training and
      fitting. In four of five patients, the sEMG test tool accurately predicted the
      suitability for further myoelectric training based on SHAP outcome measures. (P1:
      "Poor" function in the sEMG test tool corresponded to 54/100 in the SHAP test;
      P2: Good: 85; P3: Good: 81; P4: Average: 78). One patient scored well during sEMG
      testing, but was unmotivated during SHAP testing. (Good: 50) Therefore, the
      surface EMG test tool may predict achievable control skills to a high extent,
      validated with the SHAP, but requires further clinical testing to validate this
      technique. 

PMID- 25941911
TI  - Reply to: GPR120 local regulation might explain the contradictory pro/anti
      inflammatory effects of omega-3 PUFA observed in gestational tissues.

PMID- 25941910
TI  - Computation of tooth axes of existent and missing teeth from 3D CT images.
AB  - Orientations of tooth axes are important quantitative information used in dental
      diagnosis and surgery planning. However, their computation is a complex problem,
      and the existing methods have respective limitations. This paper proposes new
      methods to compute 3D tooth axes from 3D CT images for existent teeth with single
      root or multiple roots and to estimate 3D tooth axes from 3D CT images for
      missing teeth. The tooth axis of a single-root tooth will be determined by
      segmenting the pulp cavity of the tooth and computing the principal direction of
      the pulp cavity, and the estimation of tooth axes of the missing teeth is modeled
      as an interpolation problem of some quaternions along a 3D curve. The proposed
      methods can either avoid the difficult teeth segmentation problem or improve the
      limitations of existing methods. Their effectiveness and practicality are
      demonstrated by experimental results of different 3D CT images from the clinic. 

PMID- 25941912
TI  - Cuvette carryover with the gentamicin assay on the Beckman AU480 analyser.

PMID- 25941913
TI  - Total folate and 5-methyltetrahydrofolate in the cerebrospinal fluid of children:
      correlation and reference values.
AB  - BACKGROUND: Cerebral folate deficiency (CFD) may be underdiagnosed, as it
      manifests with various non-specific neurological symptoms. The diagnosis of CFD
      requires a determination of 5-methyltetrahydrofolate (5MTHF) in the cerebrospinal
      fluid (CSF), which is available in a limited number of specialized laboratories.
      In clinical biochemistry laboratories, total folate (TF) determination in serum
      or plasma is routinely performed by automated analyzers. The aim of this study is
      to determine whether the automated assay of CSF TF is a helpful screening tool
      for CFD. METHODS: We analyzed CSF samples collected from 73 pediatric patients.
      We measured CSF TF, serum TF, and CSF 5MTHF in 73, 70, and 48 patients,
      respectively. The assay of 5MTHF was conducted by a newly developed system
      utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS). We
      investigated the correlation between TF and 5MTHF in the CSF. RESULTS: There was
      a strong positive correlation between CSF TF and 5MTHF (rho=0.930, p<0.0001,
      n=48). Age was negatively correlated with CSF TF (rho=-0.557, p<0.0001, n=51),
      serum TF (rho=-0.457, p=0.0008, n=51), and CSF 5MTHF (rho=-0.387, p=0.0263,
      n=33), but not with the CSF/serum TF ratio. CONCLUSIONS: The automated assay of
      CSF TF is helpful to estimate CSF 5MTHF. The CSF TF assay may have a significant
      impact on the early diagnosis of CFD, because clinicians have better access to it
      than the 5MTHF assay.

PMID- 25941914
TI  - Perivascular adipose tissue, inflammation and insulin resistance: link to
      vascular dysfunction and cardiovascular disease.
AB  - Obesity is a leading risk factor for the development of type 2 diabetes mellitus
      (DM2) and cardiovascular disease (CVD), however the underlying mechanisms still
      remain to be fully uncovered. It is now well accepted that dysfunctional adipose
      tissue in conditions of obesity is a critical source of inflammation that impacts
      the cardiovascular system and contributes to CVD. Although traditionally visceral
      adipose tissue has been linked to increased CVD risk, there is mounting interest
      in the role that fat accumulation around the vasculature plays in the
      pathogenesis of vascular dysfunction. Perivascular adipose tissue (PVAT) is in
      intimate contact with large, medium and small diameter arterial beds in several
      tissues, and has been shown to control vascular function as well as remodeling.
      PVAT does not merely mirror visceral adipose tissue changes seen in obesity, but
      has unique features that impact vascular biology. In lean individuals PVAT exerts
      vasodilatory and anti-inflammatory functions, however obesity results in PVAT
      inflammation, characterized by imbalance between pro- and anti-inflammatory cells
      as wells as adipokines. PVAT inflammation promotes insulin resistance in the
      vasculature, thus resulting in impaired insulin-mediated vasodilatory responses
      and vascular remodeling. In this review we address current knowledge about the
      mechanisms that link PVAT inflammation to insulin resistance and vascular
      dysfunction. Indeed, PVAT emerges as a novel type of adipose tissue that
      participates in the pathogenesis of CVD, independently to a large extent to
      visceral adipose tissue. 

PMID- 25941915
TI  - Retinol binding protein 4 and its membrane receptors: a metabolic perspective.
AB  - Nearly a decade of intense research has passed since the first report linking
      circulating retinol binding protein 4 (RBP4) to the development of insulin
      resistance. By now, a variety of underlying mechanisms have been identified; some
      of them are adherent to the canonical role of this circulating protein, which is
      to transport and deliver retinol to target tissues, and others that seem rather
      independent of retinol transport. Despite all these efforts, a consensus in the
      basic principles of RBP4's metabolic effects has not been reached and some
      controversy remains. Using this as an opportunity, we here review and discuss
      current data on RBP4's action on insulin sensitivity and its dependency on
      retinol homeostasis. We pay special attention to the involvement of RBP4 membrane
      receptors that were identified during these years, such as 'stimulated by
      retinoic acid 6' (STRA6), and whose identification added another layer of
      complexity to RBP4's diverse actions. A better understanding of RBP4's functions
      might allow its therapeutic exploitations, urgently needed in our period that is
      defined by an epidemic increase in metabolic diseases such as obesity and type 2
      diabetes. 

PMID- 25941916
TI  - A mutual information estimator with exponentially decaying bias.
AB  - A nonparametric estimator of mutual information is proposed and is shown to have
      asymptotic normality and efficiency, and a bias decaying exponentially in sample
      size. The asymptotic normality and the rapidly decaying bias together offer a
      viable inferential tool for assessing mutual information between two random
      elements on finite alphabets where the maximum likelihood estimator of mutual
      information greatly inflates the probability of type I error. The proposed
      estimator is illustrated by three examples in which the association between a
      pair of genes is assessed based on their expression levels. Several results of
      simulation study are also provided. 

PMID- 25941917
TI  - In vitro antioxidant and anti-lipoperoxidative activities of bark extracts of
      Xylopia aethiopica against ion-mediated toxicity on liver homogenates.
AB  - Reactive oxygen species (ROS), products of normal cell metabolism may cause
      damage to biological macromolecules leading to severe health threats when they
      are present in high concentrations. Aromatic plants contain phytochemicals rich
      of antioxidants that prevent oxidant formation or scavenge oxidants produced
      under oxidative stress conditions. In the present study, we investigated the free
      radical scavenging effects, the antioxidant and ion toxicity preventive effect of
      Xylopia aethiopica (X. aethiopica), a plant of the family of Annonaceae used as
      spice in Cameroon. The scavenging properties of extracts of X. aethiopica were
      tested on 2, 2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), hydroxyl
      (OH), 2,2'-azinobis(3-ethylbenzthiazoline)-6-sulfonic acid (ABTS) radicals. The
      total antioxidant capacity was assayed by ferric reducing ability of plasma
      (FRAP), phosphomolybdenum antioxidant power (PAP), reduction assays. The
      protective potential was carried on superoxide dismutase (SOD), catalase and
      peroxidases. The results showed that both the ethanolic (BEE) and the
      hydroethanolic (BEH) extracts from the barks of X. aethiopica scavenged all the
      tested radicals. The sample BEH showed the highest total antioxidant capacity
      both in the FRAP and the PAP. This result was positively correlated to its higher
      phenolic content (30.74+/-0.44 CAE/g dried extract). The higher protective
      capacity of BEH on SOD, catalase and peroxidase activities was comparable to that
      of the vitamin C used as standard. In conclusion, X. aethiopica has a higher
      antioxidant and protective potential against ion-mediated oxidative damage and
      may be considered as a potential drug against metal-mediated toxicity.

PMID- 25941918
TI  - Clinical prospects of IGF-signaling system components study in ovarian cancer
      patients.
AB  - Among various auto/paracrine growth-regulating signaling pathways an important
      role belongs to that of insulin-like growth factors (IGFs) and insulin. IGF
      signaling system is actively involved in the regulation of both normal ovarian
      function and ovarian tumor growth. On the one hand, all members of this system
      are expressed in malignant ovarian epithelial cells, and the prognostic
      significance of this expression has been revealed for some of them in ovarian
      cancer patients in several studies. On the other hand, circulating IGFs/IGFBPs
      levels have not been undoubtedly associated with ovarian cancer risk or disease
      progression, but some of them can be regarded as supplementary serological
      ovarian cancer markers. An important route to the clinical application of IGF
      signaling system studies in ovarian cancer is the growing possibility of using
      specific molecular targeted agents to suppress its growth-stimulating and other
      activities. However, the introduction of such agents to practical oncology has
      met serious problems, with the main difficulties resulting from the absence of
      reliable predictive molecular markers and metabolic side effects due to the tight
      connection between IGF-signaling and insulin-regulated processes. The prognostic
      and diagnostic values of various IGF system components and the current state of
      corresponding molecular targeted therapies development for ovarian cancer are
      reviewed. 

PMID- 25941919
TI  - Gene-gene interaction of MU-opioid receptor and GluR5 kainate receptor subunit is
      associated with smoking behavior in a Greek population: presence of a dose allele
      effect.
AB  - BACKGROUND: Components of nicotine reward system can potentially influence
      smoking behavior. The MU-opioid receptor (OPRM1) binds the endogenous opioid
      peptide beta-endorphin and mediates the reinforcing effects of nicotine, while
      the GluR5 kainate receptor subunit (encoded by GRIK1 gene), a binding site for
      known mediators of glutamate neurotransmission, potentially affects the
      glutaminergic system that is also indirectly implicated in the reward system.
      METHODS: In the present study, OPRM1 A118G and GRIK1 rs2832407C>A polymorphisms
      and their interactions were analyzed in 132 smoking initiators (SI) and 144 non
      initiators (NI) of Greek origin, using the PCR-RFLP method. RESULTS: No
      differences were found in the genotype or allele distribution of OPRM1 A118G and
      GRIK1 rs2832407C>A between SI and NI. However, we found a significant interaction
      of OPRM1 A118G and GRIK1 rs2832407C>A genotypes associated with smoking
      initiation in a model adjusted for age, sex, BMI and type 2 diabetes mellitus
      (odds ratio=1.341, 95% CI 1.024-1.755, p=0.033). A dose effect of OPRM1 and GRIK1
      variant alleles was present. Increased number of variant alleles (from 0 to 4)
      was associated with smoking initiation in the same adjusted model (odds
      ratio=1.537, 95% CI 1.030-2.293, p=0.036). CONCLUSIONS: Smoking phenotype is a
      complex interaction of genetic and environmental factors. In the present study,
      we have shown that gene-gene interaction of components of different systems
      associated with nicotine reinforcing effects, such as OPRM1 and GRIK1, rather
      than one gene polymorphism, is associated with smoking behavior.

PMID- 25941920
TI  - Comparison of the myotoxic effects of levobupivacaine, bupivacaine, and
      ropivacaine: an electron microscopic study.
AB  - The aim of this study was to investigate the myotoxic effects of bupivacaine,
      ropivacaine, and levobupivacaine which were applied intramuscularly to rat
      skeletal muscle. Forty Wistar-Albino rats were divided into four groups. In the
      study, .5% bupivacaine (Group B), .5% ropivacaine (Group R), .5% levobupivacaine
      (Group L), or .9% normal saline (Group SF) was applied intramuscularly to the
      right gastrocnemius muscle of rats. The rats in each group were sacrificed on the
      second day after injection. Sections of muscle samples were stained with
      hematoxylin-eosin for light microscopic investigation and prepared for the
      evaluation of ultrastructural changes in the subcellular level with transmission
      electron microscopy. All three local anesthetic agents caused qualitatively
      similar skeletal muscle damage. The most observed muscle damage was in Group B,
      muscle damage of Group R was less than that of Group B, and the least damage was
      seen in Group L quantitatively. Electron microscopic examination of each group
      that caused cellular damage was qualitatively similar. The most subcellular
      damage was observed in the group receiving bupivacaine, less was seen in the
      ropivacaine group, and the least was observed in the levobupivacaine group. The
      results indicated that bupivacaine caused more myotoxic damage than the other two
      agents in the skeletal muscle of rats and that levobupivacaine caused less
      myotoxic damage than both bupivacaine and ropivacaine at the cell and tissue
      levels. 

PMID- 25941921
TI  - RMR Estimation Model Accuracy Using Air Displacement Plethysmography-Derived Body
      Composition Measures in Young Adults.
AB  - OBJECTIVE: Predictive equations derived from regression techniques based on large
      samples are extensively utilized in estimating resting metabolic rate (RMR). Body
      composition assessments utilize model equations to estimate RMR. However, the
      agreement of these predictive models with indirect calorimetery (IC) has come
      into question. Our aim is to investigate the agreement of RMR estimation models
      using air displacement plethysmography (ADP) measures against a gas exchange IC
      system (RMR-C). METHODS: Sixty-six participants (25 men, 41 women) completed the
      study. RMR measurements were obtained from IC and ADP within 10 minutes of one
      another. IC RMR estimates were tested against 9 other validated models using ADP
      measures via analysis of variance (ANOVA) techniques with multiple comparisons
      testing and Bland-Altman analysis. RESULTS: Based on the ANOVA, the Nelson (1992)
      model underpredicted RMR compared to IC (p < 0.001). The Dore et al. (1982) model
      was the best predictor of RMR compared to the IC measures (p = 0.907).
      DISCUSSION: The current RMR estimation model using ADP measures underpredicts
      total caloric needs. The Dore et al. (1982) model more accurately predicted RMR
      in the entire sample.

PMID- 25941922
TI  - Lentivirus-Mediated RNAi silencing targeting ERCC1 reverses cisplatin resistance
      in cisplatin-resistant ovarian carcinoma cell line.
AB  - The aim of the study was to investigate the potential mechanisms that
      interferencing of excision repair cross-complementing gene 1 (ERCC1) mediated by
      lentiviral vector in cisplatin-resistant ovarian cancer SKOV3/DDP cells. The
      human platinum-resistant ovarian carcinoma cell line SKOV3/DDP was transfected by
      pLVX-shRNA lentivirus. Interference efficiency for ERCC1 by lentiviruses
      transfection was detected by real-time polymerase chain reaction and western blot
      assay. CCK-8 assay was used for cell proliferation on cell resistance after
      transfection with ERCC1. Effects of cell apoptosis and cell cycles were detected
      by flow cytometry. The expression levels of ERCC1 were significantly suppressed
      in SKOV3/DDP cells after stably transfecting with shERCC1-recombinant plasmid.
      The results of cell viability assay demonstrated that interference with ERCC1
      gene increased the sensitivity of SKOV3/DDP cells to cisplatin (p<0.01). ERCC1
      gene-specific silencing promoted cell apoptosis of SKOV3/DDP cells (p<0.01)
      detected by flow cytometry. Cell cycle analysis results showed that the
      proportion of cells in G1 and S phase decreased, while the proportion of G2 phase
      cells increased in ERCC1-silencing cells. The differences were statistically
      significant (p<0.01), which demonstrated that stable interferencing with ERCC1
      induced the cells arrest in G2 phase after being treated by DDP and silencing the
      expression of ERCC1 inhibited cell proliferation by preventing the progression of
      cell mitosis. ERCC1 gene silencing effectively reversed SKOV3/DDP cell resistance
      to cisplatin and increased sensitivity to cisplatin resistance in cisplatin
      resistant ovarian cancer cells. Interference of ERCC1 promoted the apoptosis of
      SKOV3/DDP cells and prevented cell mitosis by inducing G0/G1 phase arrest. Thus,
      ERCC1 could be a potential therapeutic target for the therapy of cisplatin
      resistant ovarian cancer and it would provide new ideas for epigenetic therapy of
      drug-resistant epithelial ovarian cancer. 

PMID- 25941923
TI  - Interethnic relationships of CYP2D6 variants in native and Mestizo populations
      sharing the same ecosystem.
AB  - AIM: To analyze the distribution of CYP2D6 variants in two ethnically-related
      Mexican Native and Mestizo populations cohabitating the same econiche and their
      relationships with a distant Mestizo community. MATERIALS & METHODS: 314
      volunteers were genotyped for CYP2D6 gene variants (*2, *3, *4, *6, *10, *13,
      *17, *35 and *41) using predesigned TaqMan probes. CYP2D6*5 and CYP2D6 wtxN were
      assessed by XL-PCR. RESULTS: CYP2D6*1, *2, *4 and *10 variants represented above
      80.9% of total alleles. Chiapanecan communities showed low allele diversity
      compared with the northeastern population. Principal component analyses
      demonstrated clustering of both Mestizo populations. Variants associated to
      ultrarapid and poor metabolism were rare in Natives. CONCLUSION: Sharing of
      CYP2D6 alleles in both Chiapanecan populations suggests an ongoing gene-flow.
      Original submitted 8 December 2014; Revision submitted 13 February 2015.

PMID- 25941924
TI  - The Impact of a 24-h Ultra-Marathon on Circulatory Endotoxin and Cytokine
      Profile.
AB  - The study aimed to determine circulatory endotoxin concentration, cytokine
      profile, and gastrointestinal symptoms of ultra-endurance runners (UER, n=17) in
      response to a 24-h continuous ultra-marathon competition (total distance range:
      122-208 km) conducted in temperate ambient conditions (0-20  degrees C) in
      mountainous terrain. Body mass and body temperature were measured, and venous
      blood samples were taken before and immediately after competition. Samples were
      analysed for gram-negative bacterial endotoxin, C-reactive protein, cytokine
      profile, and plasma osmolality. Gastrointestinal symptoms were also monitored
      throughout competition. Mean exercise-induced body mass loss was (mean+/-SD)
      1.7+/-1.8% in UER. Pre- and post-competition plasma osmolality in UER was 286+/
      11 mOsmol.kg(-1) and 286+/-9 mOsmol.kg(-1), respectively. Pre- to post
      competition increases (p<0.05) were observed for endotoxin (37%), C-reactive
      protein (2832%), IL-6 (3 436%), IL-1beta (332%), TNF-alpha (35%), IL-10 (511%),
      and IL-8 (239%) concentrations in UER, with no change in the control group (CON;
      n=12) observed (p>0.05). Gastrointestinal symptoms were reported by 75% of UER,
      with no symptoms reported by CON. IL-10 (r=0.535) and IL-8 (r=0.503) were
      positively correlated with gastrointestinal symptoms. A 24-h continuous ultra
      marathon competition in temperate ambient conditions resulted in a circulatory
      endotoxaemia and pro-inflammatory cytokinaemia, counteracted by a compensatory
      anti-inflammatory response.

PMID- 25941925
TI  - Whey or Casein Hydrolysate with Carbohydrate for Metabolism and Performance in
      Cycling.
AB  - The protein type most suitable for ingestion during endurance exercise is
      undefined. This study compared co-ingestion of either 15 g/h whey or casein
      hydrolysate with 63 g/h fructose: maltodextrin (0.8:1) on exogenous carbohydrate
      oxidation, exercise metabolism and performance. 2 h postprandial, 8 male cyclists
      ingested either: carbohydrate-only, carbohydrate-whey hydrolysate, carbohydrate
      casein hydrolysate or placebo-water in a crossover, double-blind design during 2
      h of exercise at 60%W max followed by a 16-km time trial. Data were evaluated by
      magnitude-based inferential statistics. Exogenous carbohydrate oxidation,
      measured from (13)CO2 breath enrichment, was not substantially influenced by co
      ingestion of either protein hydrolysate. However, only co-ingestion of
      carbohydrate-casein hydrolysate substantially decreased (98% very likely
      decrease) total carbohydrate oxidation (mean+/-SD, 242+/-44; 258+/-47; 277+/-33 g
      for carbohydrate-casein, carbohydrate-whey and carbohydrate-only, respectively)
      and substantially increased (93% likely increase) total fat oxidation (92+/-14;
      83+/-27; 73+/-19 g) compared with carbohydrate-only. Furthermore, only
      carbohydrate-casein hydrolysate ingestion resulted in a faster time trial (-3.6%;
      90% CI: +/-3.2%) compared with placebo-water (95% likely benefit). However,
      neither protein hydrolysate enhanced time trial performance when compared with
      carbohydrate-only. Under the conditions of this study, ingesting carbohydrate
      casein, but not carbohydrate-whey hydrolysate, favourably alters metabolism
      during prolonged moderate-strenuous cycling without substantially altering
      cycling performance compared with carbohydrate-only. 

PMID- 25941926
TI  - Physiological Interpretation of the Slope during an Isokinetic Fatigue Test.
AB  - To assess the relationship between selected measures (the slope and average
      performance) obtained during a high intensity isokinetic fatigue test of the knee
      (FAT) and relevant measures of anaerobic and aerobic capacities. 20 well-trained
      cyclists performed 3 randomly ordered sessions involving a FAT consisting in 30
      reciprocal maximal concentric contractions of knee flexors and extensors at 180
      degrees .s(-1), a maximal continuous graded exercise test (GXT), and a Wingate
      anaerobic test (WAnT). The slope calculated from peak torque (PT) and total work
      (TW) of knee extensors was highly associated to maximal PT (r=-0.86) and maximal
      TW (r=-0.87) measured during FAT, and moderately associated to peak power output
      measured during the WAnT (r=-0.64 to -0.71). Average PT and average TW were
      highly associated to maximal PT (r=0.93) and maximal TW (r=0.96), to mean power
      output measured during WAnT (r=0.83-0.90) and moderately associated to maximal
      oxygen uptake (0.58-0.67). In conclusion, the slope is mainly determined by
      maximal anaerobic power, while average performance is a composite measure
      depending on both aerobic and anaerobic energy systems according to proportions
      that are determined by the duration of the test. 

PMID- 25941927
TI  - Design, delivery, and outcomes from an interprofessional fall prevention course.
AB  - This article describes the development, delivery, and outcomes from an
      interprofessional evidence-based falls management course for undergraduate and
      graduate students. The 3-credit elective course was developed by a gerontological
      social work and nursing faculty member in partnership with community-based
      housing and case management organizations. Creation of the course was in response
      to a mandate by the Health Resources and Services Administration, funding source
      for federal Geriatric Education Centers, to train interprofessional students
      using an evidence-based approach while tying the outcomes to improved health
      measures in the target population. Therefore, this article describes student
      competencies pre- and postcourse completion and outcomes of community-dwelling
      older adults completing a Matter of Balance (MOB) program delivered by these
      students. A total of 16 students completed the course which included delivery of
      the MOB program to 41 older adults. Results indicate statistically significant
      improvements in student outcomes from a pre/post falls knowledge test. For older
      adult participants, many screened positively for fall risk factors pre-post MOB
      participation showed statistically significant improvements in falls efficacy,
      control, management, and overall mobility. Opportunities and challenges
      associated with course delivery are also described. 

PMID- 25941928
TI  - Abnormal mitochondrial function and impaired granulosa cell differentiation in
      androgen receptor knockout mice.
AB  - In the ovary, the paracrine interactions between the oocyte and surrounded
      granulosa cells are critical for optimal oocyte quality and embryonic
      development. Mice lacking the androgen receptor (AR-/-) were noted to have
      reduced fertility with abnormal ovarian function that might involve the promotion
      of preantral follicle growth and prevention of follicular atresia. However, the
      detailed mechanism of how AR in granulosa cells exerts its effects on oocyte
      quality is poorly understood. Comparing in vitro maturation rate of oocytes, we
      found oocytes collected from AR-/- mice have a significantly poor maturating rate
      with 60% reached metaphase II and 30% remained in germinal vesicle breakdown
      stage, whereas 95% of wild-type AR (AR+/+) oocytes had reached metaphase II.
      Interestingly, we found these AR-/- female mice also had an increased frequency
      of morphological alterations in the mitochondria of granulosa cells with reduced
      ATP generation (0.18 +/- 0.02 vs. 0.29 +/- 0.02 uM/mg protein; p < 0.05) and
      aberrant mitochondrial biogenesis. Mechanism dissection found loss of AR led to a
      significant decrease in the expression of peroxisome proliferator-activated
      receptor gamma (PPARgamma) co-activator 1-beta (PGC1-beta) and its sequential
      downstream genes, nuclear respiratory factor 1 (NRF1) and mitochondrial
      transcription factor A (TFAM), in controlling mitochondrial biogenesis. These
      results indicate that AR may contribute to maintain oocyte quality and fertility
      via controlling the signals of PGC1-beta-mediated mitochondrial biogenesis in
      granulosa cells.

PMID- 25941929
TI  - Generation of Rho Zero Cells: Visualization and Quantification of the mtDNA
      Depletion Process.
AB  - Human mitochondrial DNA (mtDNA) is located in discrete DNA-protein complexes, so
      called nucleoids. These structures can be easily visualized in living cells by
      utilizing the fluorescent stain PicoGreen. In contrary, cells devoid of
      endogenous mitochondrial genomes (rho0 cells) display no mitochondrial staining
      in the cytoplasm. A modified restriction enzyme can be targeted to mitochondria
      to cleave the mtDNA molecules in more than two fragments, thereby activating
      endogenous nucleases. By applying this novel enzymatic approach to generate mtDNA
      depleted cells the destruction of mitochondrial nucleoids in cultured cells could
      be detected in a time course. It is clear from these experiments that mtDNA
      depleted cells can be seen as early as 48 h post-transfection using the depletion
      system. To prove that mtDNA is degraded during this process, mtDNA of transfected
      cells was quantified by real-time PCR. A significant decline could be observed 24
      h post-transfection. Combination of both results showed that mtDNA of transfected
      cells is completely degraded and, therefore, rho0 cells were generated within 48
      h. Thus, the application of a mitochondrially-targeted restriction endonuclease
      proves to be a first and fast, but essential step towards a therapy for mtDNA
      disorders.

PMID- 25941931
TI  - Escherichia coli Maltose-Binding Protein Induces M1 Polarity of RAW264.7
      Macrophage Cells via a TLR2- and TLR4-Dependent Manner.
AB  - Maltose-binding protein (MBP) is a critical player of the maltose/maltodextrin
      transport system in Escherichia coli. Our previous studies have revealed that MBP
      nonspecifically induces T helper type 1 (Th1) cell activation and activates
      peritoneal macrophages obtained from mouse. In the present study, we reported a
      direct stimulatory effect of MBP on RAW264.7 cells, a murine macrophage cell
      line. When stimulated with MBP, the production of nitric oxide (NO), IL-1beta, IL
      6 and IL-12p70, and the expressions of CD80, MHC class II and inducible nitric
      oxide synthase (iNOS) were all increased in RAW264.7 cells, indicating the
      activation and polarization of RAW264.7 cells into M1 macrophages induced by MBP.
      Further study showed that MBP stimulation upregulated the expression of TLR2 and
      TLR4 on RAW264.7 cells, which was accompanied by subsequent phosphorylation of
      IkappaB-alpha and p38 MAPK. Pretreatment with anti-TLR2 or anti-TLR4 antibodies
      largely inhibited the phosphorylation of IkappaB-alpha and p38 MAPK, and greatly
      reduced MBP-induced NO and IL-12p70 production, suggesting that the MBP-induced
      macrophage activation and polarization were mediated by TLR2 and TLR4 signaling
      pathways. The observed results were independent of lipopolysaccharide
      contamination. Our study provides a new insight into a mechanism by which MBP
      enhances immune responses and warrants the potential application of MBP as an
      immune adjuvant in immune therapies. 

PMID- 25941932
TI  - Effects of dietary vitamin E on fertility functions in poultry species.
AB  - Vitamin E is found in high quantities in vegetable oils. Although vitamin E has
      multiple functions in humans and animals, its key function is protecting cells
      from oxidative damage. Since its discovery, several studies have demonstrated
      that vitamin E deficiency causes impaired fertility in humans and lab animals.
      However, the effects of vitamin E deficiency or of its supplementation on the
      fertility of farm animals, particularly on poultry, are less well studied.
      Therefore, a comprehensive review of the effects of dietary vitamin E on the
      fertility of poultry species is needed in order to understand the beneficial role
      of vitamin E in the maintenance of sperm and egg qualities. Based on the
      observations reviewed here, we found that a moderate amount of vitamin E in
      poultry diet significantly protects semen/sperm qualities in male birds and egg
      qualities in female birds via decreasing the lipid peroxidation in semen/sperms
      and eggs. This review provides an overall understanding of the effects of dietary
      vitamin E on fertility functions in poultry species. 

PMID- 25941930
TI  - Structural Insights into tRNA Dynamics on the Ribosome.
AB  - High-resolution structures at different stages, as well as biochemical, single
      molecule and computational approaches have highlighted the elasticity of tRNA
      molecules when bound to the ribosome. It is well acknowledged that the inherent
      structural flexibility of the tRNA lies at the heart of the protein synthesis
      process. Here, we review the recent advances and describe considerations that the
      conformational changes of the tRNA molecules offer about the mechanisms grounded
      in translation. 

PMID- 25941933
TI  - Quantitative Real-Time PCR Analysis of YKL-40 and Its Comparison with Mammalian
      Chitinase mRNAs in Normal Human Tissues Using a Single Standard DNA.
AB  - YKL-40 (YKL for the first three N-terminal residues of a 40 kDa protein) belongs
      to a group of human chitinase-like proteins (CLPs), which are similar to
      chitinases but lack chitinolytic activity. YKL-40 mRNA and its protein levels
      have been reported elevated in multiple disorders including asthma, cystic
      fibrosis, rheumatoid arthritis and malignant tumors. Here, we quantified the YKL
      40 mRNA levels and compared them with chitinases and housekeeping genes in normal
      human tissues. To establish the quantitative real-time PCR (qPCR) system for
      evaluation of relative YKL-40 mRNA levels, we constructed a human standard DNA
      molecule by ligating cDNAs of YKL-40, two mammalian chitinases and two
      housekeeping genes in a one-to-one ratio. We generated cDNAs from various normal
      human tissues and analyzed the YKL-40 mRNA expression levels using a qPCR system
      with the standard DNA. We found that YKL-40 mRNA is present widely in human
      tissues while its expression patterns exhibit clear tissue specificity. Highest
      YKL-40 mRNA levels were detected in the liver, followed by kidney, trachea and
      lung. The levels of YKL-40 mRNA in the kidney and liver were more than 100-times
      higher than those of chitotriosidase mRNA. Our study provides for the first time
      a comprehensive analysis of the relative expression levels of YKL-40 mRNA versus
      mammalian chitinases in normal human tissues. 

PMID- 25941934
TI  - Aminolevulinic acid-mediated photodynamic therapy of human meningioma: an in
      vitro study on primary cell lines.
AB  - OBJECTIVE: Five-aminolevulinic acid (5-ALA)-induced porphyrins in malignant
      gliomas are potent photosensitizers. Promising results of ALA-PDT (photodynamic
      therapy) in recurrent glioblastomas have been published. Recently, 5-ALA-induced
      fluorescence was studied in meningioma surgery. Here, we present an experimental
      study of ALA-PDT in an in vitro model of primary meningioma cell lines. METHODS:
      We processed native tumor material obtained intra-operatively within 24 h for
      cell culture. Epithelial membrane antigen (EMA) immunohistochemistry was
      performed after the first passage to confirm that cells were meningioma cells.
      For 5-ALA-PDT treatment, about 5000 cells per well were seeded in 20 wells of a
      blank 96-well plate. Each block of 4 wells was inoculated with 150 uL of 0, 25,
      50 and 100 ug/mL 5-ALA solutions; one block was used as negative control without
      5-ALA and without PDT. Following incubation for 3 h PDT was performed using a
      laser (635 nm, 18.75 J/cm2). The therapeutic response was analyzed by the water
      soluble tetrazolium salt (WST-1) cell viability assay 90 min after PDT. RESULTS:
      5-ALA-PDT was performed in 14 primary meningioma cell lines. EMA expression was
      verified in 10 primary cell cultures. The remaining 4 were EMA negative and PDT
      was without any effect in these cultures. All 10 EMA-positive cell lines showed a
      significant and dose-dependent decrease in viability rate (p < 0.001). Cell
      survival at 5-ALA concentrations of 12.5, 25, 50 and 100 MUg/mL was 96.5% +/-
      7.6%, 67.9% +/- 29.9%, 24.0% +/- 16.7% and 13.8% +/- 7.5%, respectively. For the
      negative controls (no 5-ALA/PDT and ALA/no PDT), the viability rates were 101.72%
      +/- 3.5% and 100.17% +/- 3.6%, respectively. The LD50 for 5-ALA was estimated
      between 25 and 50 ug/mL. CONCLUSION: This study reveals dose-dependent cytotoxic
      effects of 5-ALA-PDT on primary cell lines of meningiomas. Either 5-ALA or PDT
      alone did not affect cell survival. Further efforts are necessary to study the
      potential therapeutic effects of 5-ALA-PDT in vivo.

PMID- 25941936
TI  - Sasa quelpaertensis Leaf Extract Inhibits Colon Cancer by Regulating Cancer Cell
      Stemness in Vitro and in Vivo.
AB  - A rare subpopulation of cancer cells, termed cancer stem cells (CSCs), may be
      responsible for tumor relapse and resistance to conventional chemotherapy. The
      development of a non-toxic, natural treatment for the elimination of CSCs is
      considered a strategy for cancer treatment with minimal side effects. In the
      present study, the potential for Sasa quelpaertensis leaf extract (SQE) and its
      two bioactive compounds, tricin and p-coumaric acid, to exert anti-CSC effects by
      suppressing cancer stemness characteristics were evaluated in colon cancer cells.
      CD133+CD44+ cells were isolated from HT29 and HCT116 cell lines using flow
      activated cell sorting (FACs). SQE treatment was found to significantly suppress
      the self-renewal capacity of both cell lines. SQE treatment was also associated
      with the down-regulation of beta-catenin and phosphorylated GSK3beta, while
      significantly enhancing cell differentiation by up-regulating CK20 expression and
      blocking the expression of several stem cell markers, including DLK1, Notch1, and
      Sox-2. In vivo, SQE supplementation suppressed tumor growth in a xenograft model
      by down-regulating stem cell markers and beta-catenin as well as HIF-1alpha
      signaling. Compared with two bioactive compounds of SQE, SQE exhibited the most
      effective anti-CSC properties. Taken together, these results provide evidence
      that SQE inhibits colon cancer by regulating the characteristics of CSCs. 

PMID- 25941937
TI  - Evaluation and Selection of Appropriate Reference Genes for Real-Time
      Quantitative PCR Analysis of Gene Expression in Nile Tilapia (Oreochromis
      niloticus) during Vaccination and Infection.
AB  - qPCR as a powerful and attractive methodology has been widely applied to
      aquaculture researches for gene expression analyses. However, the suitable
      reference selection is critical for normalizing target genes expression in qPCR.
      In the present study, six commonly used endogenous controls were selected as
      candidate reference genes to evaluate and analyze their expression levels,
      stabilities and normalization to immune-related gene IgM expression during
      vaccination and infection in spleen of tilapia with RefFinder and GeNorm
      programs. The results showed that all of these candidate reference genes
      exhibited transcriptional variations to some extent at different periods. Among
      them, EF1A was the most stable reference with RefFinder, followed by 18S rRNA,
      ACTB, UBCE, TUBA and GAPDH respectively and the optimal number of reference genes
      for IgM normalization under different experiment sets was two with GeNorm.
      Meanwhile, combination the Cq (quantification cycle) value and the recommended
      comprehensive ranking of reference genes, EF1A and ACTB, the two optimal
      reference genes, were used together as reference genes for accurate analysis of
      immune-related gene expression during vaccination and infection in Nile tilapia
      with qPCR. Moreover, the highest IgM expression level was at two weeks post
      vaccination when normalized to EF1A, 18S rRNA, ACTB, and EF1A together with ACTB
      compared to one week post-vaccination before normalizing, which was also
      consistent with the IgM antibody titers detection by ELISA. 

PMID- 25941935
TI  - Pathogenesis of brain edema and investigation into anti-edema drugs.
AB  - Brain edema is a potentially fatal pathological state that occurs after brain
      injuries such as stroke and head trauma. In the edematous brain, excess
      accumulation of extracellular fluid results in elevation of intracranial
      pressure, leading to impaired nerve function. Despite the seriousness of brain
      edema, only symptomatic treatments to remove edema fluid are currently available.
      Thus, the development of novel anti-edema drugs is required. The pathogenesis of
      brain edema is classified as vasogenic or cytotoxic edema. Vasogenic edema is
      defined as extracellular accumulation of fluid resulting from disruption of the
      blood-brain barrier (BBB) and extravasations of serum proteins, while cytotoxic
      edema is characterized by cell swelling caused by intracellular accumulation of
      fluid. Various experimental animal models are often used to investigate
      mechanisms underlying brain edema. Many soluble factors and functional molecules
      have been confirmed to induce BBB disruption or cell swelling and drugs targeted
      to these factors are expected to have anti-edema effects. In this review, we
      discuss the mechanisms and involvement of factors that induce brain edema
      formation, and the possibility of anti-edema drugs targeting them. 

PMID- 25941938
TI  - Imperfect asymmetry: The mechanism governing asymmetric partitioning of damaged
      cellular components during mitosis.
AB  - Aging is universally associated with organism-wide dysfunction and a decline in
      cellular fitness. From early development onwards, the efficiency of self-repair,
      energy production, and homeostasis all decrease. Due to the multiplicity of
      systems that undergo agingrelated decline, the mechanistic basis of organismal
      aging has been difficult to pinpoint. At the cellular level, however, recent work
      has provided important insight. Cellular aging is associated with the
      accumulation of several types of damage, in particular damage to the proteome and
      organelles. Groundbreaking studies have shown that replicative aging is the
      result of a rejuvenation mechanism that prevents the inheritance of damaged
      components during division, thereby confining the effects of aging to specific
      cells, while removing damage from others. Asymmetric inheritance of misfolded and
      aggregated proteins, as well as reduced mitochondria, has been shown in yeast.
      Until recently, however, it was not clear whether a similar mechanism operates in
      mammalian cells, which were thought to mostly divide symmetrically. Our group has
      recently shown that vimentin establishes mitotic polarity in immortalized
      mammalian cells, and mediates asymmetric partitioning of multiple factors through
      direct interaction. These findings prompt a provocative hypothesis: that
      intermediate filaments serve as asymmetric partitioning modules or "sponges"
      that, when expressed prior to mitosis, can "clean" emerging cells of the damage
      they have accumulated. 

PMID- 25941939
TI  - Short Communication: HIV-1 Subtype B in the Dominican Republic: Evolution and
      Molecular Epidemiology.
AB  - The Caribbean region has the world second highest incidence rate of acquired
      immunodeficiency syndrome. The island of Hispaniola is composed of two sovereign
      nations: the Dominican Republic and Haiti. Together, they account for more than
      85% of HIV/AIDS cases in the Caribbean; and the Dominican Republic alone has
      approximately 46,000 (33,000-59,000) HIV-1-infected adults and children. Despite
      this, the magnitude of the genetic variability and evolution of the HIV-1 virus
      in the Dominican Republic is unclear. In the current study, we analyzed 195
      reverse transcriptase (RT) sequences obtained from the Los Alamos HIV database.
      The data were used to assess the course of the viral epidemic over time in the
      Dominican Republic, using a coalescent approach. Based on the data, we estimated
      that the timing of the most recent common ancestor (tMRCA) of local HIV-1 subtype
      B emerged in 1963, approximately. In addition, the Bayesian analysis provided new
      information that suggests that the epidemic in the Dominican Republic experienced
      a significant decrease in relative genetic diversity in the past 2 decades. The
      results suggest that adherence to antiretroviral therapy, adequate prevention
      campaigns, and better access to health care may be altering the virus's evolution
      in the Dominican Republic. 

PMID- 25941941
TI  - The role of the Utah Artificial Ear project in the development of the modern
      cochlear implant.
AB  - The cochlear implant has provided the first substantial restoration of a human
      sense by a medical intervention. This accomplishment was brought about by the
      efforts, over a 50+ year period, of many individuals in laboratories around the
      world. In this paper, we recount the history of one of the early projects - the
      Utah Artificial Ear project. In 1970 researchers at the University of Utah began
      work on an auditory prosthesis. A critical early decision was to create a
      'transparent' link between external signal processing and the electrodes
      implanted in the cochlea, i.e., a percutaneous pedestal. The pedestal allowed D.
      Eddington, then a graduate student, to conduct, in 1975-1978, the first thorough,
      parametric, psychophysical studies of electrical stimulation of the cochlea in
      multiple human volunteers. The early work by Eddington and colleagues evolved in
      1983 into the 4-channel, Ineraid cochlear implant. Many years later, highly
      effective, modern signal processing algorithms, e.g., continuous interleaved
      sampling (CIS), fine structure processing (FSP), and virtual channel processing,
      were first tested and developed with the aid of Ineraid patients fit with
      pedestals of the Utah design. Because for many years the Ineraid provided as high
      a level of speech understanding as that provided by other devices and because the
      percutaneous pedestal allowed the first testing of many modern signal processing
      algorithms, the Utah Artificial Ear project may be viewed as one of the most
      valuable research projects in the history of cochlear implants. 

PMID- 25941942
TI  - Electronic Structure and Magnetic Properties of CuFeS2.
AB  - Chalcopyrite (CuFeS2) is an antiferromagnetic semiconductor with unusual magnetic
      and electrical properties, which are still not clearly understood. Neutron
      diffraction experiments reveal a phase transition at ~50 K that has been
      attributed to an unexpected appearance of magnetic moments on Cu ions, having a
      paramagnetic arrangement down to 50 K and then ordering to an antiferromagnetic
      state at lower temperatures. In this study we use DFT-based computational methods
      to investigate the electronic structure and magnetic properties of CuFeS2 in
      order to obtain a reliable source of information for the interpretation of the
      observed magnetic behavior, and in particular to shed some light on the magnetic
      behavior of copper atoms in this compound. We have calculated the electronic
      structure of the ground and low-energy magnetically excited states and deduced a
      set of exchange coupling constants that are used afterward in classical Monte
      Carlo simulations to obtain magnetic susceptibility data, which compare
      successfully with our experimental results above ~170 K. From our results it can
      be inferred that copper atoms remain in a diamagnetic state in this temperature
      range, although spin delocalization from neighboring iron atoms results in a non
      negligible spin density on the copper atoms at high temperatures. 

PMID- 25941940
TI  - HDAC inhibition attenuates cardiac hypertrophy by acetylation and deacetylation
      of target genes.
AB  - Pharmacological histone deacetylase (HDAC) inhibitors attenuate pathological
      cardiac remodeling and hypertrophic gene expression; yet, the direct histone
      targets remain poorly characterized. Since the inhibition of HDAC activity is
      associated with suppressing hypertrophy, we hypothesized histone acetylation
      would target genes implicated in cardiac remodeling. Trichostatin A (TSA)
      regulates cardiac gene expression and attenuates transverse aortic constriction
      (TAC) induced hypertrophy. We used chromatin immunoprecipitation (ChIP) coupled
      with massive parallel sequencing (ChIP-seq) to map, for the first time, genome
      wide histone acetylation changes in a preclinical model of pathological cardiac
      hypertrophy and attenuation of pathogenesis with TSA. Pressure overload-induced
      cardiac hypertrophy was associated with histone acetylation of genes implicated
      in cardiac contraction, collagen deposition, inflammation, and extracellular
      matrix identified by ChIP-seq. Gene set enrichment analysis identified NF-kappa B
      (NF-kappaB) transcription factor activation with load induced hypertrophy.
      Increased histone acetylation was observed on the promoters of NFkappaB target
      genes (Icam1, Vcam1, Il21r, Il6ra, Ticam2, Cxcl10) consistent with gene
      activation in the hypertrophied heart. Surprisingly, TSA attenuated pressure
      overload-induced cardiac hypertrophy and the suppression of NFkappaB target genes
      by broad histone deacetylation. Our results suggest a mechanism for
      cardioprotection subject to histone deacetylation as a previously unknown target,
      implicating the importance of inflammation by pharmacological HDAC inhibition.
      The results of this study provides a framework for HDAC inhibitor function in the
      heart and argues the long held views of acetylation is subject to more
      flexibility than previously thought. 

PMID- 25941943
TI  - The Reaction Mechanism with Free Energy Barriers for Electrochemical Dihydrogen
      Evolution on MoS2.
AB  - We report density functional theory (M06L) calculations including Poisson
      Boltzmann solvation to determine the reaction pathways and barriers for the
      hydrogen evolution reaction (HER) on MoS2, using both a periodic two-dimensional
      slab and a Mo10S21 cluster model. We find that the HER mechanism involves
      protonation of the electron rich molybdenum hydride site (Volmer-Heyrovsky
      mechanism), leading to a calculated free energy barrier of 17.9 kcal/mol, in good
      agreement with the barrier of 19.9 kcal/mol estimated from the experimental
      turnover frequency. Hydronium protonation of the hydride on the Mo site is 21.3
      kcal/mol more favorable than protonation of the hydrogen on the S site because
      the electrons localized on the Mo-H bond are readily transferred to form
      dihydrogen with hydronium. We predict the Volmer-Tafel mechanism in which
      hydrogen atoms bound to molybdenum and sulfur sites recombine to form H2 has a
      barrier of 22.6 kcal/mol. Starting with hydrogen atoms on adjacent sulfur atoms,
      the Volmer-Tafel mechanism goes instead through the M-H + S-H pathway. In
      discussions of metal chalcogenide HER catalysis, the S-H bond energy has been
      proposed as the critical parameter. However, we find that the sulfur-hydrogen
      species is not an important intermediate since the free energy of this species
      does not play a direct role in determining the effective activation barrier.
      Rather we suggest that the kinetic barrier should be used as a descriptor for
      reactivity, rather than the equilibrium thermodynamics. This is supported by the
      agreement between the calculated barrier and the experimental turnover frequency.
      These results suggest that to design a more reactive catalyst from edge exposed
      MoS2, one should focus on lowering the reaction barrier between the metal hydride
      and a proton from the hydronium in solution. 

PMID- 25941944
TI  - Baccalaureate Nursing Students' Knowledge of and Attitudes Toward Older Adults.
AB  - Preparing nurses to care for a growing population of older adults is one of the
      most significant challenges for nursing education. The purpose of the current
      study was to describe baccalaureate nursing students' knowledge of and attitudes
      toward older adults, and explore the impact of a gerontological nursing course on
      their knowledge and attitudes. Results showed that students who had prior
      experience with older adults had significantly more positive attitudes toward
      them. Although students who participated in a gerontological nursing course had
      significantly higher knowledge scores than the comparison group, no significant
      difierence was noted in overall attitude. In addition, students who were enrolled
      in the gerontological nursing course or had prior experience with older adults
      were more likely to report plans to work with this population after graduation.
      Students who participated in interviews with older adults found the experience
      meaningful and their attitudes regarding older adults were largely positive.

PMID- 25941945
TI  - In Vitro Multiparameter Assay Development Strategy toward Differentiating
      Macrophage Responses to Inhaled Medicines.
AB  - Although foamy macrophages (FMPhi) are commonly observed during nonclinical
      development of medicines for inhalation, there are no accepted criteria to
      differentiate adaptive from adverse FMPhi responses in drug safety studies. The
      purpose of this study was to develop a multiparameter in vitro assay strategy to
      differentiate and characterize different mechanisms of drug-induced FMPhi.
      Amiodarone, staurosporine, and poly(vinyl acetate) nanoparticles were used to
      induce distinct FMPhi phenotypes in J774A.1 cells, which were then compared with
      negative controls. Treated macrophages were evaluated for morphometry, lipid
      accumulation, gene expression, apoptosis, cell activation, and phagocytosis.
      Analysis of vacuolization (number/area vacuoles per cell) and phospholipid
      content revealed inducer-dependent distinctive patterns, which were confirmed by
      electron microscopy. In contrast to the other inducers, amiodarone increased
      vacuole size rather than number and resulted in phospholipid accumulation. No
      pronounced dysregulation of transcriptional activity or apoptosis was observed in
      response to sublethal concentrations of all inducers. Functionally, FMPhi
      induction did not affect macrophage activation by lipopolysaccharide, but it
      reduced phagocytic capacity, with different patterns of induction, severity, and
      resolution observed with the different inducers. An in vitro multiparameter assay
      strategy is reported that successfully differentiates and characterizes
      mechanisms leading to FMPhi induction by different types of agents. 

PMID- 25941946
TI  - Assessing the authenticity of commercial deep-sea drinking water by chemical and
      isotopic approaches.
AB  - This study combines stable isotopes and chemical elements with statistical
      principal component analysis (PCA) to assess the authenticity of bottled
      commercial drinking water desalinized from deep seawater in the Taiwan market.
      Isotopic results indicate that true bottled deep-sea drinking water (DSDW)
      exhibits about 0 0/00 for both delta(2)H and delta(18)O values, which are values
      similar to those of open seawater. By comparison, suspected counterfeit DSDW
      products display delta(2)H and delta(18)O values of around -51 0/00 and -8 0/00,
      respectively. These values are representative of terrestrial freshwater. In
      addition, suspected counterfeit DSDWs have delta and electrical conductivity
      values similar to a mixed water (MW) product that was manufactured by purifying
      terrestrial freshwater and adulterating this with small amounts of brine.
      Furthermore, PCA results indicate the chemical constitution of suspected DSDW
      products to be similar to the MW product which falls between purified terrestrial
      freshwater and desalinized open seawater. These similarities imply that suspected
      counterfeit DSDW products are manufactured in a similar manner to the declared MW
      product. This study demonstrates how combining knowledge of stable water isotopes
      and PCA can be used in assessing the authenticity of commercial DSDW products.
      The method should be of great interest to similar investigations elsewhere. 

PMID- 25941947
TI  - Medicare and Medicaid Reimbursement Rates for Nursing Homes Motivate Select
      Culture Change Practices But Not Comprehensive Culture Change.
AB  - Components of nursing home (NH) culture change include resident-centeredness,
      empowerment, and home likeness, but practices reflective of these components may
      be found in both traditional and "culture change" NHs. We use mixed methods to
      examine the presence of culture change practices in the context of an NH's payer
      sources. Qualitative data show how higher pay from Medicare versus Medicaid
      influences implementation of select culture change practices, and quantitative
      data show NHs with higher proportions of Medicare residents have significantly
      higher (measured) environmental culture change implementation. Findings indicate
      that heightened coordination of Medicare and Medicaid could influence NH
      implementation of reform practices. 

PMID- 25941948
TI  - Momentum-resolved spectroscopy of a Fermi liquid.
AB  - We consider a recent momentum-resolved radio-frequency spectroscopy experiment,
      in which Fermi liquid properties of a strongly interacting atomic Fermi gas were
      studied. Here we show that by extending the Brueckner-Goldstone model, we can
      formulate a theory that goes beyond basic mean-field theories and that can be
      used for studying spectroscopies of dilute atomic gases in the strongly
      interacting regime. The model hosts well-defined quasiparticles and works across
      a wide range of temperatures and interaction strengths. The theory provides
      excellent qualitative agreement with the experiment. Comparing the predictions of
      the present theory with the mean-field Bardeen-Cooper-Schrieffer theory yields
      insights into the role of pair correlations, Tan's contact, and the Hartree mean
      field energy shift. 

PMID- 25941949
TI  - Why Hart found narrow ecospheres--a minor science mystery solved.
AB  - AIMS: To explain why two NASA computer simulation studies in the 1970s (Hart,
      1978 , 1979 ) briefly rocked the subfield of astrobiology and SETI studies by
      showing very narrow habitable zones (HZs) for solar-type stars. Although other
      studies later supported wider HZs, it was never clear why the Hart simulations
      found the narrow limits they did. RESULTS: Investigation of the state of climate
      studies and radiative transfer models in the period 1960-1970 provides a likely
      explanation. CONCLUSION: Hart's findings were in line with earlier results,
      preventing him from noticing that his radiation model was inadequate.

PMID- 25941951
TI  - Potentiation of the effect of a commercial animal feed additive mixed with
      different probiotic yeast strains on the adsorption of aflatoxin B1.
AB  - This study potentiates the adsorbent effect for aflatoxin B1 (AFB1) of a
      commercial additive (CA) of animal feed, containing inactive lysate of three
      Saccharomyces cerevisiae strains, active enzymes, adsorbents and a selenium-amino
      acid complex, when the additive was mixed separately with three S. cerevisiae
      strains. Levels of AFB1 of 20 and 50 ng g(-1) were used to determine the binding
      capacity of different concentrations of CA alone and in the presence of yeast
      strains, as well as toxin desorption, under gastrointestinal conditions. The
      viability of yeasts in the presence of CA was evaluated. The results show that
      the CA did not affect the viability of the yeast strains assayed. CA alone showed
      a low percentage adsorption. At 20 and at 50 ng g(-1), CA was highly efficient in
      adsorbing AFB1 when combined with RC016 and RC012 strains respectively.
      Desorption of AFB1 by CA alone and in combination with the yeasts increased with
      increasing levels of CA. The results demonstrate the improvement of CA in AFB1
      adsorption once it is mixed with live yeasts.

PMID- 25941950
TI  - Electronic system with memristive synapses for pattern recognition.
AB  - Memristive synapses, the most promising passive devices for synaptic
      interconnections in artificial neural networks, are the driving force behind
      recent research on hardware neural networks. Despite significant efforts to
      utilize memristive synapses, progress to date has only shown the possibility of
      building a neural network system that can classify simple image patterns. In this
      article, we report a high-density cross-point memristive synapse array with
      improved synaptic characteristics. The proposed PCMO-based memristive synapse
      exhibits the necessary gradual and symmetrical conductance changes, and has been
      successfully adapted to a neural network system. The system learns, and later
      recognizes, the human thought pattern corresponding to three vowels, i.e. /a /,
      /i /, and /u/, using electroencephalography signals generated while a subject
      imagines speaking vowels. Our successful demonstration of a neural network system
      for EEG pattern recognition is likely to intrigue many researchers and stimulate
      a new research direction. 

PMID- 25941952
TI  - Membrane potential and ion partitioning in an erythrocyte using the Poisson
      Boltzmann equation.
AB  - In virtually all mammal cells, we can observe a much higher concentration of
      potassium ions inside the cell and vice versa for sodium ions. Classical theories
      ignore the specific ion effects and the difference in the thermodynamic reference
      states between intracellular and extracellular environments. Usually, this
      differential ion partitioning across a cell membrane is attributed exclusively to
      the active ion transport. Our aim is to investigate how much the dispersion
      forces contribute to active ion pumps in an erythrocyte (red blood cell) as well
      as the correction of chemical potential reference states between intracellular
      and extracellular environments. The ionic partition and the membrane potential in
      an erythrocyte are analyzed by the modified Poisson-Boltzmann equation,
      considering nonelectrostatic interactions between ions and macromolecules.
      Results show that the nonelectrostatic potential calculated by Lifshitz theory
      has only a small influence with respect to the high concentration of K(+) in the
      intracellular environment in comparison with Na(+). 

PMID- 25941954
TI  - Peginterferon beta-1a (Plegridy) for multiple sclerosis.
AB  - Pegylated interferon beta-1a (Plegridy) injected subcutaneously every 2 weeks
      appears to be similar in its efficacy and adverse effects to older interferon
      formulations that must be injected more frequently.

PMID- 25941953
TI  - Hydrogen evolution catalyzed by cobalt diimine-dioxime complexes.
AB  - Mimicking photosynthesis and producing solar fuels is an appealing way to store
      the huge amount of renewable energy from the sun in a durable and sustainable
      way. Hydrogen production through water splitting has been set as a first-ranking
      target for artificial photosynthesis. Pursuing that goal requires the development
      of efficient and stable catalytic systems, only based on earth abundant elements,
      for the reduction of protons from water to molecular hydrogen. Cobalt complexes
      based on glyoxime ligands, called cobaloximes, emerged 10 years ago as a first
      generation of such catalysts. They are now widely utilized for the construction
      of photocatalytic systems for hydrogen evolution. In this Account, we describe
      our contribution to the development of a second generation of catalysts, cobalt
      diimine-dioxime complexes. While displaying similar catalytic activities as
      cobaloximes, these catalysts prove more stable against hydrolysis under strongly
      acidic conditions thanks to the tetradentate nature of the diimine-dioxime
      ligand. Importantly, H2 evolution proceeds via proton-coupled electron transfer
      steps involving the oxime bridge as a protonation site, reproducing the mechanism
      at play in the active sites of hydrogenase enzymes. This feature allows H2 to be
      evolved at modest overpotentials, that is, close to the thermodynamic equilibrium
      over a wide range of acid-base conditions in nonaqueous solutions. Derivatization
      of the diimine-dioxime ligand at the hydrocarbon chain linking the two imine
      functions enables the covalent grafting of the complex onto electrode surfaces in
      a more convenient manner than for the parent bis-bidentate cobaloximes.
      Accordingly, we attached diimine-dioxime cobalt catalysts onto carbon nanotubes
      and demonstrated the catalytic activity of the resulting molecular-based
      electrode for hydrogen evolution from aqueous acetate buffer. The stability of
      immobilized catalysts was found to be orders of magnitude higher than that of
      catalysts in the bulk. It led us to evidence that these cobalt complexes, as
      cobaloximes and other cobalt salts do, decompose under turnover conditions where
      they are free in solution. Of note, this process generates in aqueous phosphate
      buffer a nanoparticulate film consisting of metallic cobalt coated with a cobalt
      oxo/hydroxo-phosphate layer in contact with the electrolyte. This novel material,
      H2-CoCat, mediates H2 evolution from neutral aqueous buffer at low
      overpotentials. Finally, the potential of diimine-dioxime cobalt complexes for
      light-driven H2 generation has been attested both in water/acetonitrile mixtures
      and in fully aqueous solutions. All together, these studies hold promise for the
      construction of molecular-based photoelectrodes for H2 evolution and further
      integration in dye-sensitized photoelectrochemical cells (DS-PECs) able to
      achieve overall water splitting. 

PMID- 25941955
TI  - Concentrated insulin glargine (Toujeo) for diabetes.
AB  - Toujeo, the new 300 IU/mL formulation of insulin glargine, is as effective as
      insulin glargine 100 IU/mL (Lantus) in lowering HbA1c, and might cause less
      hypoglycemia.

PMID- 25941956
TI  - Extended-release hydrocodone (Hysingla ER) for pain.
AB  - Hysingla ER, the second single-ingredient extended-release hydrocodone product to
      become available in the US, is formulated for once-daily use. Zohydro ER is dosed
      twice daily and costs more. Both Hysingla ER and the new formulation of Zohydro
      ER have abuse-deterrent properties, but they will still be subject to misuse.

PMID- 25941957
TI  - Testosterone nasal gel (Natesto) for hypogonadism.
AB  - In one study, Natesto nasal gel administered intranasally 3 times daily was
      effective in raising low serum testosterone levels into the normal range in
      patients with hypogonadism. Whether patients will find this method of
      administration more acceptable than an intramuscular injection every 2-4 weeks or
      once-daily application to the skin remains to be determined. Based on the lack of
      convincing evidence of benefit in older men and concerns about its safety, the
      FDA has warned against using testosterone to treat hypogonadism due solely to
      aging.

PMID- 25941958
TI  - Blinatumomab (Blincyto) for acute lymphoblastic leukemia.
AB  - Blinatumomab (Blincyto) was effective in inducing a complete remission in 33% of
      patients with relapsed or refractory Philadelphia chromosome-negative (Ph-) B
      cell precursor acute lymphoblastic leukemia (ALL). Grade 3 or 4 adverse effects
      occur frequently.

PMID- 25941959
TI  - Safety and Efficacy of Epi-Bowman Keratectomy in Photorefractive Keratectomy and
      Corneal Collagen Cross-Linking: A Pilot Study.
AB  - PURPOSE: The purpose of this study is to compare the efficacy and safety of Epi
      Bowman Keratectomy (EBK) using Epi-clearTM epikeratome with a mechanical scraper
      for corneal epithelium debridement during photorefractive keratectomy (PRK) and
      corneal collagen cross-linking (CXL). METHODOLOGY: Sixty eyes of 30 patients
      undergoing PRK and 44 eyes of 44 patients undergoing CXL were included in this
      study. In the PRK group, one eye of each patient underwent EBK and the other eye
      epithelial debridement with a mechanical scraper. In the CXL group, 22 eyes of 22
      patients underwent EBK and the other 22 eyes with a mechanical scraping to remove
      the epithelium. Intra-operative spectral domain optical coherence tomography (SD
      OCT; Bioptigen Inc, Durham, NC) was performed to evaluate the integrity of
      Bowman's membrane following epithelial removal. The time taken for epithelial
      removal, post-operative pain score using the Wong-Baker's pain scale, time for
      epithelial healing, and the epithelial profile using the Optovue (Optovue Inc.
      Fremont, CA) during the healing was observed and analyzed between the two groups
      and subgroups. RESULTS: Intra-operative SD OCT showed a smooth and undamaged
      Bowman's membrane when EBK was performed. Post-operative pain was significantly
      less (p < 0.01 in the PRK group and p < 0.001 in the CXL group) with faster
      epithelial healing (p < 0.001 in the PRK group and p < 0.0001 in the CXL group)
      in the EBK subgroup as compared with the mechanical scraper subgroup. Epithelial
      profiling during the healing phase showed an edematous epithelium in the initial
      2 weeks in the mechanical scraper subgroup while the EBK subgroup showed minimal
      epithelial edema lasting up to a week with regularized and smooth corneal
      epithelium healing. CONCLUSION: Epi-Bowman Keratectomy appears to be an effective
      and safe method of corneal epithelial debridement with negligible damage to
      Bowman's membrane and the surrounding epithelium leading to early healing thereby
      reducing the post-operative pain and complications.

PMID- 25941960
TI  - Spinal form cerebrotendinous xanthomatosis patient with long spinal cord lesion.
AB  - CONTEXT: Cerebrotendinous xanthomatosis (CTX) is an autosomal recessively
      inherited lipid storage disease caused by mutation in the CYP27A1 gene. Spinal
      form CTX is a rare clinical subgroup of CTX and only 14 patients from 11 families
      have been reported to date. Here, we report the first Asian patient with spinal
      form CTX showing characteristic radiological findings. FINDINGS: The patient, a
      46-year-old Japanese male, developed sensory disturbance of the lower legs at 39
      and spastic gait at 46 years of age. Spinal cord magnetic resonance imaging (MRI)
      revealed a long hyperintense lesion involving lateral corticospinal tracts and
      gracile tracts in the cervical and thoracic cord on T2-weighted images. Gallium
      67 (67Ga) scintigraphy revealed abnormal uptake in the Achilles tendons and the
      serum cholestanol level was elevated. CYP27A1 gene analysis identified homozygous
      missense mutation, c.1214G>A (p.R405Q). The patient was treated with atorvastatin
      monotherapy, which reduced serum cholestanol to less than 50% of the pretreatment
      level. CONCLUSION: Spinal form CTX should be considered in the differential
      diagnosis of cryptogenic myelopathy, especially in patients with a long spinal
      cord lesion, as treatment with chenodeoxycholic acid and/or competitive
      inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase reverse
      the metabolic derangement and prevent the neurologiccal dysfunction.

PMID- 25941961
TI  - Evaluation of Prognostic Nutritional Index in Patients Undergoing Radical Surgery
      with Nonsmall Cell Lung Cancer.
AB  - The prognostic nutritional index (PNI) has been reported to be a prognostic
      indicator in some malignant tumors. However, its prognostic value in nonsmall
      cell lung cancer (NSCLC) has not been fully investigated. A retrospective review
      of 1416 patients with NSCLC who underwent radical surgery between January 2006
      and December 2011 was conducted. To obtain optimal cutoff levels of PNI, running
      log-rank statistics was applied. Survival was calculated by the Kaplan-Meier
      method. The prognostic significance of PNI, together with various
      clinicopathological factors, was evaluated by multivariate analysis. The optimal
      cutoff point for PNI was 52. The 1-, 3-, and 5-yr survival rates in patients with
      PNI of less than 52 were 80.0%, 61.3%, and 50.4%, respectively, and were
      significantly more unfavorable than those in patients with PNI 52 or higher
      (84.7%, 71.5%, and 60.3%, respectively, P < 0.001). Multivariate analysis
      suggested that gender (P = 0.026), age (P < 0.001), PNI (P = 0.005),
      differentiation (P = 0.024), pathology T category (P = 0.003), and pathology N
      category (P < 0.001) were revealed to be independent prognostic factors. Our
      results indicate that PNI is an independent predictor of survival for patients
      undergoing radical surgery with NSCLC. 

PMID- 25941962
TI  - Placenta Derived Adherent Cell (PDAC) Interaction and Response on Extracellular
      Matrix Isolated from Human Placenta t.
AB  - A method was developed to isolate extracellular matrix from the human placenta
      (pECM). The isolated material is composed primarily of collagen, in addition to,
      elastin, fibronectin, laminin, and glycosaminoglycans (GAGs). The pECM is
      isolated as a water insoluble paste. This paste can be molded into sheets, tubes,
      and other 3-D structures that are stable at room temperature. This report
      describes the interaction of the pluripotent progenitor cells (PDACs) with the
      isolated pECM. The stem cells used in this study are of human placental origin
      (placenta derived adherent cells or PDACs) and have a phenotype described as
      CD200+, CD105+, CD10+, CD34-, and CD45-. The PDACs bind to and proliferate on the
      pECM, and are stimulated to secrete soluble fibronectin. They actively assemble
      the soluble fibronectin into a complex network of detergent-insoluble
      extracellular matrix fibrils. While proliferating on the pECM, PDACs secrete key
      cytokines at levels well above that observed on tissue-treated tissue culture
      plates. These cytokines included monocyte chemoattractant protein (MCP-1), IL-6,
      and IL-8, all of which are important participants in wound healing processes.
      These results suggest the feasibility of designing a combination product of pECM
      with PDACs to augment repair processes in nonhealing deep wounds and in diabetic
      ulcers. 

PMID- 25941963
TI  - Duration of disease, neuropathic symptoms, and plantar sensitivity in patients
      with diabetes with and without previous plantar ulceration .
AB  - This study compared the duration of disease, the prevalence of neuropathy
      symptoms, and plantar insensitivity among subjects with diabetic neuropathy, with
      and without previous history of plantar ulcers, to a nondiabetic group of
      subjects. Correlations were made between the neuropathic symptoms observed and
      the results of sensory tests. Thermal and tactile sensitivities and sensitive
      chronaxie were measured in the control group (CG, n = 19), a diabetic neuropathic
      group (DG, n = 16), and a diabetic neuropathic group with previous history of
      plantar ulceration (UDG, n = 9). Plantar sensitivity was investigated in 5 areas
      of the plantar surface of both feet: heel, midfoot, lateral forefoot, medial
      forefoot, and hallux. The neuropathy symptoms were investigated using the
      Michigan Neuropathy Screening Instrument (MNSI). The neuropathic groups did not
      differ in duration of diabetes onset (DG = 13 years +/- 8; UDG = 14 years +/- 5;
      P = 0.243) and they presented similar mean for symptoms according to MNSI score
      (DG = 6.94 +/- 1.81; UDG = 6.78 +/- 2.44; P = 0.352). The frequency of subjects
      with abnormal sensitivity was higher in UDG. The MNSI showed moderate correlation
      with tactile sensitivity (r <-0.42, P <0.05). Patients with diabetic neuropathy
      and an ulcer had decreased sensitivity in their feet. The symptoms may indicate
      loss of sensation, but symptoms alone are not able to differentiate between
      neuropathic subjects with different progressions of diabetic peripheral
      neuropathy (DPN). Duration of diabetes and symptoms did not explain the severity
      of neuropathy in people with a diabetic ulcer. 

PMID- 25941964
TI  - Use of negative pressure wound therapy in the management of wound dehiscence in
      a pregnant patient.
AB  - The case reported herein describes use of a negative pressure wound therapy
      (NPWT) system in the treatment of surgical wound infection and dehiscence with
      exposed, gravid uterus after emergent small bowel resection in a woman 25 weeks
      pregnant. 

PMID- 25941965
TI  -  Limited access dressing.
AB  - The Limited Access Dressing (LAD) combines the principles of moist wound healing
      and topical negative pressure dressing along with a provision of an additional
      port (12-14 FR size tube) for instilling antimicrobial solution/gas of choice (to
      make wound environment aerobic/anaerobic) without any need to change the
      dressing. The efficacy of the dressing technique was proven by a study of 39
      cases, including 12 cases with exposed bone and tendon (July 2004 to March 2005)
      where wounds were prepared by LAD II and split-thickness skin grafting with LAD
      II. Efficacy of LAD was assessed by observing the time to development of healthy
      granulation tissue and by the quantity of graft take under LAD by day 10. For the
      wounds studied, an average of 1.51 LAD (range 1-3) was required to develop
      granulation tissue fit for skin grafting. The average number of days required to
      prepare the wound under LAD was 17.05 days. An average of 1.03 LAD was required
      for covering the wound with skin graft (range 1 to 2; median 1) and overall graft
      take under LAD was 99.87%. In 24 of 39 wounds, an average of 33.83 days of
      treatment with conventional dressing (range 7 to 120 days; median 22.5 days)
      could not achieve healthy granulation. When these wounds were switched to LAD,
      wound preparation took an average of 13.2 days (range 3 to 32 days; median 12
      days). It was concluded that LAD is a safe and effective alternative to
      conventional dressing methods. . 

PMID- 25941966
TI  - Multifunctional imidazobenzothiadiazole probe displaying solvatofluorochromism
      and ability to form ion-pair complexes in solid state and in solution.
AB  - Fluorescent solid 5-pyridylimidazobenzothiadiazole displays a remarkable
      solvatofluorochromism and with Zn(AcO)2 and Cd(AcO)2, either in solution or under
      solvent-free conditions, forms ion-pair complexes that in the solid state can be
      discriminated and separated by fluorescence measurements and selective extraction
      with diethyl ether or chloroform. 

PMID- 25941967
TI  - Polar Solvents Trigger Formation of Reverse Micelles.
AB  - We use molecular dynamics simulations and molecular thermodynamics to investigate
      the formation of reverse micelles in a system of surfactants and nonpolar
      solvents. Since the early observation of reverse micelles, the question has been
      whether the existence of polar solvent molecules such as water is the driving
      force for the formation of reverse micelles in nonpolar solvents. In this work,
      we use a simple coarse-grained model of surfactants and solvents to show that a
      small number of polar solvent molecules triggers the formation of large permanent
      aggregates. In the absence of polar molecules, both the thermodynamic model and
      molecular simulations show that small aggregates are more populated in the
      solution and larger ones are less frequent as the system evolves over time. The
      size and shape of reverse micelles depend on the size of the polar core: the
      shape is spherical for a large core and ellipsoidal for a smaller one. Using the
      coarse-grained model, we also investigate the effect of temperature and
      surfactant tail length. Our results reveal that the number of surfactant
      molecules in the micelle decreases as the temperature increases, but the average
      diameter does not change because the size of the polar core remains invariant. A
      reverse micelle with small polar core attracts fewer surfactants when the tail is
      long. The uptake of solvent particles by a micelle of longer surfactant tail is
      less than shorter ones when the polar solvent particles are initially distributed
      randomly. 

PMID- 25941968
TI  - Ultrafast primary processes of the stable neutral organic radical, 1,3,5
      triphenylverdazyl, in liquid solution.
AB  - Femtosecond spectroscopy with hyperspectral white-light detection was used to
      elucidate the ultrafast primary processes of the thermodynamically stable organic
      radical, 1,3,5-triphenylverdazyl, in liquid acetonitrile solution at room
      temperature. The radical was excited with optical pulses having a duration of 39
      fs and a center wavelength of 800 nm thereby accessing its energetically lowest
      electronically excited state (D1). The apparent spectrotemporal response is
      understood in terms of an ultrafast primary D1-to-D0 internal conversion that
      generates the electronic ground state of the radical in a highly vibrationally
      excited fashion within a few hundred femtoseconds. The replenished electronic
      ground state subsequently undergoes vibrational cooling on a time scale of a few
      picoseconds. The instantaneous absorption spectra of the radical derived from the
      femtosecond pump-probe data are analyzed within the Sulzer-Wieland formalism for
      calculating the electronic spectra of "hot" polyatomic molecules. The pump-probe
      spectra together with transient anisotropy data in the region of the D0 -> D1
      ground-state bleach gives evidence for an additional transient absorption that
      arises from a dark excited state, which gains oscillator strength with increasing
      vibrational excitation of the radical by virtue of vibronic coupling. 

PMID- 25941969
TI  - Safety, Health, and Methodological Aspects of Plant Sterols and Stanols.

PMID- 25941970
TI  - Hydrophilic, bactericidal nanoheater-enabled reverse osmosis membranes to improve
      fouling resistance.
AB  - Polyamide (PA) semipermeable membranes typically used for reverse osmosis water
      treatment processes are prone to fouling, which reduces the amount and quality of
      water produced. By synergistically coupling the photothermal and bactericidal
      properties of graphene oxide (GO) nanosheets, gold nanostars (AuNS), and
      hydrophilic polyethylene glycol (PEG) on PA reverse osmosis membrane surfaces, we
      have dramatically improved fouling resistance of these membranes. Batch fouling
      experiments from three classes of fouling are presented: mineral scaling (CaCO3
      and CaSO4), organic fouling (humic acid), and biofouling (Escherichia coli).
      Systematic analyses and a variety of complementary techniques were used to
      elucidate fouling resistance mechanisms from each layer of modification on the
      membrane surface. Both mineral scaling and organic fouling were significantly
      reduced in PA-GO-AuNS-PEG membranes compared to other membranes. The PA-GO-AuNS
      PEG membrane was also effective in killing all near-surface bacteria compared to
      PA membranes. In the PA-GO-AuNS-PEG membrane, the GO nanosheets act as templates
      for in situ AuNS growth, which then facilitated localized heating upon
      irradiation by an 808 nm laser inactivating bacteria on the membrane surface.
      Furthermore, AuNS in the membrane assisted PEG in preventing mineral scaling on
      the membrane surface. In flow-through flux and foulant rejection tests, PA-GO
      AuNS-PEG membranes performed better than PA membranes in the presence of CaSO4
      and humic acid model foulants. Therefore, the newly suggested membrane surface
      modifications will not only reduce fouling from RO feeds, but can improve overall
      membrane performance. Our innovative membrane design reported in this study can
      significantly extend the lifetime and water treatment efficacy of reverse osmosis
      membranes to alleviate escalating global water shortage from rising energy
      demands. 

PMID- 25941972
TI  - Alkali-Resistant Mechanism of a Hollandite DeNOx Catalyst.
AB  - A thorough understanding of the deactivation mechanism by alkalis is of great
      importance for rationally designing improved alkali-resistant deNOx catalysts,
      but a traditional ion-exchange mechanism cannot often accurately describe the
      nature of the deactivation, thus hampering the development of superior catalysts.
      Here, we establish a new exchange-coordination mechanism on the basis of the
      exhaustive study on the strong alkali resistance of a hollandite manganese oxide
      (HMO) catalyst. A combination of isothermal adsorption measurements of ammonia
      with X-ray absorption near-edge structure spectra and X-ray photoelectron spectra
      reveals that alkali metal ions first react with protons from Bronsted acid sites
      of HMO via the ion exchange. Synchrotron X-ray diffraction patterns and extended
      X-ray absorption fine structure spectra coupled with theoretical calculations
      demonstrate that the exchanged alkali metal ions are subsequently stabilized at
      size-suitable cavities in the HMO pores via a coordination model with an energy
      savings. This exchange-coordination mechanism not only gives a wholly convincing
      explanation for the intrinsic nature of the deactivation of the reported
      catalysts by alkalis but also provides a strategy for rationally designing
      improved alkali-resistant deNOx catalysts in general. 

PMID- 25941973
TI  - Changing the magnetic properties of microstructure by directing the self-assembly
      of superparamagnetic nanoparticles.
AB  - Magnetic nanoparticles (MNPs) in a liquid dispersion can be organized through
      controlled self-assembly by applying an external magnetic field that regulates
      inter-particle interactions. Thus, micro- and nanostructures of desired
      morphology and superlattice geometry that show emergent magnetic properties can
      be fabricated. We describe how superferromagnetism, which is a specific type of
      emergence, can be produced. Here, superparamagnetic nanoparticles that show no
      individual residual magnetization are organized into structures with substantial
      residual magnetization that behave as miniature permanent magnets. We investigate
      the emergence of superferromagnetism in an idealized system consisting of two
      MNPs, by considering the influence that interparticle magnetostatic interactions
      have on the dynamics of the magnetic moments. We use this model to illustrate the
      design principles for self-assembly in terms of the choice of material and MNP
      particle size. We simulate the dynamics of the interacting magnetic moments by
      applying the stochastic Landau-Lifshitz-Gilbert equation to verify our
      principles. The findings enable a method to pattern material magnetization with
      submicron resolution, a useful feature that has potential applications for
      magnetic recording and microfluidic particle traps. The analysis also yields
      useful empirical generalizations that could facilitate other theoretical
      developments. 

PMID- 25941971
TI  - Plant Sterols, Stanols, and Sitosterolemia.
AB  - Phytosterolemia (sitosterolemia) is a rare autosomal recessive sterol storage
      disease caused by mutations in either of the adenosine triphosphate (ATP) binding
      cassette transporter genes; (ABC) G5 or ABCG8, leading to impaired elimination of
      plant sterols and stanols, with their increased accumulation in the blood and
      tissues. Thus the disease is characterized by substantially elevated serum plant
      sterols and stanols, with moderate to high plasma cholesterol levels, and
      increased risk of premature atherosclerosis. Hematologic abnormalities including
      macrothrombocytopenia, stomatocytosis and hemolysis are frequently observed in
      sitosterolemia patients. Currently, ezetimibe, a sterol absorption inhibitor, is
      used as the routine treatment for sitosterolemia, with reported improvement in
      plant sterol levels and hemolytic parameters. This review summarizes the research
      related to the health impact of plant sterols and stanols on sitosterolemia. 

PMID- 25941974
TI  - Understanding the role of dysfunctional post-trauma cognitions in the co
      occurrence of Posttraumatic Stress Disorder and Generalized Anxiety Disorder: Two
      trauma samples.
AB  - This report focuses on the co-occurrence of PTSD-GAD and examines a factor that
      could operate to maintain both conditions, specifically negative post-trauma
      cognitions about the self, the world, and self-blame. Two separate help-seeking
      samples were examined: (a) a mixed gender sample of 301 individuals who had
      experienced a serious motor vehicle accident (MVA), a single incident, non
      interpersonal trauma; and (b) a sample of 157 women who had experienced intimate
      partner violence (IPV), a recurrent, interpersonal trauma. When examined at the
      diagnostic level, posttraumatic cognitions for one diagnosis did not vary as a
      function of whether the other diagnosis was present. In the MVA sample, both
      diagnosed PTSD and GAD were associated with elevations in negative thoughts about
      the self. Diagnosed GAD was also significantly associated with negative thoughts
      about the world. In the IPV sample, diagnosed PTSD was associated with elevations
      in negative thoughts about the self only. When continuously measured PTSD and GAD
      were examined, results indicated that negative thoughts about the self showed
      significant simultaneous associations with PTSD and GAD in both samples. In the
      MVA sample, negative thoughts about the world and self-blame showed significant
      associations with PTSD but not with GAD. In the IPV sample, negative thoughts
      about the world and self-blame were not significantly associated with either PTSD
      or GAD. Results are discussed in light of current treatment models for these
      conditions, with emphasis on the potential for addressing transdiagnostic
      processes as a more effective approach to treating comorbid conditions following
      trauma. 

PMID- 25941975
TI  - Serum levels of homocysteine, folate and vitamin B12 in patients with vitiligo
      before and after treatment with narrow band ultraviolet B phototherapy and in a
      group of controls.
AB  - The association between vitamin B12, folate, homocysteine and vitiligo were
      studied in several studies, but the results are contradictory. Narrow-band
      ultraviolet B (NBUVB) phototherapy is now considered as a gold standard for the
      treatment of diffuse vitiligo. The effects of NBUVB phototherapy on both vitamin
      B12, folate and homocysteine levels have not been studied in vitiligo patients
      yet. Serum levels of vitamin B12, folate and homocysteine were measured in
      vitiligo patients and control group and also both before and after NBUVB
      phototherapy in vitiligo patients. While levels of homocysteine in patients with
      vitiligo were significantly higher than controls (16.9+/-8.4 vs. 10. 9+/-3.4
      MUmol/L; p<0,001) vitamin B12 and folate levels were not different (p>0.05).
      NBUVB phototherapy led to a 33.7+/-21.9% (0-75%) response in patients with
      vitiligo after 80 seccions. Treatment with NBUVB improved vitiligo and decreased
      serum levels of vitamin B12 (375+/-151 vs. 346+/-119 pg/ml, p=0.024), while serum
      levels of folate and homocysteine did not change significantly after treatment
      (p=0.914, p=0.127). Further studies are needed to clarify the influence of NBUVB
      phototherapy on folate, vitamin B12 and homocysteine levels in patients with
      vitiligo. Furthermore, studies with the analysis of skin levels of homocysteine
      rather than circulating levels may be useful to elucidate the effects of
      phototherapy on homocysteine levels.

PMID- 25941976
TI  - Enzymatic Mechanism of Leishmania major Peroxidase and the Critical Role of
      Specific Ionic Interactions.
AB  - Leishmania major peroxidase (LmP) is very similar to the well-known yeast
      cytochrome c peroxidase (CcP). Both enzymes catalyze the peroxidation of
      cytochrome c. Like CcP, LmP reacts with H2O2 to form Compound I, which consists
      of a ferryl heme and a Trp radical, Fe(IV)?O;Trp(*+). Cytochrome c (Cytc) reduces
      the Trp radical to give Compound II, Fe(IV)?O;Trp, which is followed by an
      intramolecular electron transfer to give Fe(III)-OH;Trp(*+), and in the last
      step, Cytc reduces the Trp radical. In this study, we have used steady-state and
      single-turnover kinetics to improve our understanding of the overall mechanism of
      LmP catalysis. While the activity of CcP greatly increases with ionic strength,
      the kcat for LmP remains relatively constant at all ionic strengths tested.
      Therefore, unlike CcP, where dissociation of oxidized Cytc is limiting at low
      ionic strengths, association/dissociation reactions are not limiting at any ionic
      strength in LmP. We conclude that in LmP, the intramolecular electron transfer
      reaction, Fe(IV)?O;Trp to Fe(III)-OH;Trp(*+), is limiting at all ionic strengths.
      Unlike CcP, LmP depends on key intermolecular ion pairs to form the electron
      transfer competent complex. Mutating these sites causes the initial rate of
      association to decrease by 2 orders of magnitude and a substantial decrease in
      kcat. The drop in kcat is due to a switch in the rate-limiting step of the
      mutants from intramolecular electron transfer to the rate of association in
      forming the LmP-LmCytc complex. These studies show that while LmP and CcP form
      very similar complexes and exhibit similar activities, they substantially differ
      in how their activity changes as a function of ionic strength. This difference is
      primarily due to the heavy reliance of LmP on highly specific intermolecular ion
      pairs, while CcP relies mainly on nonpolar interactions. 

PMID- 25941977
TI  - Effects of ring size and polar functional groups on the glutathione peroxidase
      like antioxidant activity of water-soluble cyclic selenides.
AB  - To elucidate the effects of ring structure and a substituent on the glutathione
      peroxidase- (GPx-) like antioxidant activities of aliphatic selenides, series of
      water-soluble cyclic selenides with variable ring size and polar functional
      groups were synthesized, and their antioxidant activities were evaluated by NADPH
      coupled assay using H2O2 and glutathione (GSH) in water and also by NMR
      spectroscopy using H2O2 and dithiothreitol (DTT(red)) in methanol. Strong
      correlations were found among the GPx-like activity in water, the second-order
      rate constants for the oxidation of the selenides, and the HOMO energy levels
      calculated in water. The results support the conclusion that the oxidation
      process is the rate-determining step of the catalytic cycle. On the other hand,
      such correlations were not obtained for the activity observed in methanol. The
      optimal ring size was determined to be five. The type of substituent (NH2 < OH <
      CO2H) and the number can also control the activity, whereas the
      stereoconfiguration has only marginal effects on the activity in water. In
      methanol, however, the activity rank could not be explained by the simple
      scenarios applicable in water. 

PMID- 25941978
TI  - The Role of Psychological Symptomatology and Social Support in the Academic
      Adjustment of Previously Deployed Student Veterans.
AB  - CONTEXT: Research has indicated that returning Operation Enduring
      Freedom/Operation Iraqi Freedom (OEF/OIF) veterans are experiencing mental health
      concerns following deployment. Increasing numbers of veterans are enrolling in
      higher education institutions; there is a scarcity of empirical research
      investigating student veterans' experiences as they transition into college.
      OBJECTIVE: To examine the effects of psychological distress and social support on
      academic adjustment among a sample of student veterans who were previously
      deployed. DESIGN, SETTING, AND PARTICIPANTS: Participants were 117 military
      veterans enrolled in college. Questionnaires were administered via SurveyMonkey
      from June 2012 to April 2013. RESULTS: Results indicated that military unit
      support during deployment, current social support, anxiety, and posttraumatic
      symptoms, but not depressive symptoms, were significantly associated with
      academic adjustment. CONCLUSIONS: Results from the current study can be used by
      college administrators and counseling centers to improve service delivery and
      programming specifically for student veterans.

PMID- 25941980
TI  - Saccharide Composition of Carbohydrates Consumed during an Ultra-endurance
      Triathlon.
AB  - OBJECTIVE: Ingesting a mix of glucose and fructose during exercise increases
      exogenous carbohydrate oxidation while minimizing gastrointestinal (GI) distress.
      Several studies have suggested that a glucose-to-fructose ratio of 1.2:1 to 1:1
      is optimal. No studies have quantified saccharides consumed during a nonsimulated
      endurance event. The aim of this investigation was to quantify saccharide sources
      used during an ultra-endurance triathlon and provide a resource for athletes
      desiring to manipulate the saccharide content of carbohydrate consumed during
      training and competition. METHODS: Participant self-report and direct measurement
      were used to assess foods and beverages consumed during an ultra-endurance (70.3
      mile) triathlon. Manufacturer-supplied information, high-performance liquid
      chromatography, and the US Department of Agriculture Food Database were used to
      quantify saccharide profiles of foods and beverages. Participants reported GI
      distress during the run on a 0-10 scale. A subanalysis examined associations
      between saccharides and GI distress among participants consuming >= 50 g.h(-1) of
      carbohydrate during the swim and cycle. RESULTS: Fifty-four participants (43 men)
      used 80 foods and beverages with a unique saccharide profile. Of total
      carbohydrate, median proportions as glucose, fructose, and sucrose were 64%, 5%,
      and 10%, and only 7 foods (8.8%) had a glucose-to-fructose ratio of 1.2:1 to 1:1.
      The median glucose-to-fructose ratio of carbohydrate ingested was 2.9:1 (2.2:1
      5.3:1). Twenty participants consumed >= 50 g.h(-1) of carbohydrate during the
      swim and cycle, and significant correlations with incident GI distress at mile 1
      of the run were found for glucose (r = 0.480, p = 0.032) and fructose (r = 
      0.454, p = 0.044). CONCLUSIONS: The majority of foods and beverages consumed
      during an ultra-endurance triathlon did not contain an optimal saccharide
      profile. Furthermore, glucose intake was associated with greater GI distress
      among participants consuming a high rate of carbohydrate.

PMID- 25941981
TI  - Sulfur imidations: access to sulfimides and sulfoximines.
AB  - Being mono-aza analogues of sulfoxides and sulfones, sulfimides and sulfoximines,
      respectively, are important compounds in asymmetric synthesis, crop protection
      and medicinal chemistry. For their preparation various methods have been
      developed. In the search for the optimal synthetic approach for a given target
      compound, several parameters have to be considered which also include safety
      issues and availability of starting materials. In this tutorial review, we
      present an overview of sulfur imidation methods, classified by imidating agents
      and compounds with a related behaviour. The aim of this survey is to provide a
      practical "tool box" for the synthetic chemist by mapping the advantages and
      disadvantages associated with the use of these compounds. 

PMID- 25941982
TI  - The BE-ACTIV Project: How Research, Professional Training, Education, and
      Practice Were Integrated in a Single Clinical Trial.
AB  - This article describes how research, practice, and education were integrated in a
      National Institutes of Mental Health-funded clinical trial for treating
      depression in nursing homes. Involving undergraduate and doctoral students in
      this clinical trial supported the development of key competencies, expanded the
      professional pipeline, and provided an avenue for disseminating the treatment to
      other settings. The clinical trial served as a teaching laboratory for sixteen
      undergraduate and six doctoral students to (1) observe the culture of older
      adults in nursing homes, (2) develop and adapt clinical skills to a challenging
      patient population, (3) refine skills for collaborating in multidisciplinary
      teams, and (4) appreciate the relationship between science and practice.
      Dissemination of the intervention to nonresearch settings was served when the
      students took their skills to the settings where they launched their careers.
      Involvement of trainees in clinical trial research expands and enriches the
      capacity of the health care workforce in evidence-based practice and practice
      informed research. 

PMID- 25941983
TI  - Combined effects of repeated sauna therapy and exercise training on cardiac
      function and physical activity in patients with chronic heart failure.
AB  - PURPOSE: We investigated the combined effects of repeated sauna therapy and
      exercise training on subjective symptoms, cardiac function, daily activities and
      ambulation capacity in patients with chronic heart failure. METHODS: Fifty four
      patients including 26 patients with repeated sauna therapy and exercise training
      (combined therapy group) and 28 patients with repeated sauna therapy (monotherapy
      group) participated in the study. Repeated sauna therapy and exercise training
      were performed once a day, 5 days a week. Clinical symptoms, brain natriuretic
      peptide concentration, cardiac functions evaluated by echocardiography, cardiac
      size on chest radiography, Barthel Index (BI) and ambulation capacity were
      examined and compared between the time of hospital admission and the time of
      discharge. RESULTS: Both the groups showed significantly improved New York Heart
      Association functional class, cardiothoracic ratio, brain natriuretic peptide
      concentration, left ventricular ejection fraction, BI score and ambulation
      capacity grade. The changes of New York Heart Association functional class, BI
      score and ambulation capacity in the combined therapy group were a higher level
      of statistical significance than those in monotherapy group. Notably, significant
      between group difference was observed in the changes of BI score. CONCLUSIONS:
      The addition of exercise training programs to repeated sauna therapy may be
      efficient and effective for improvement of cardiac function and daily activities
      for patients with chronic heart failure. IMPLICATIONS OF REHABILITATION: Repeated
      sauna therapy is an effective means of improving cardiac, vascular function and
      mental health in CHF patients. Exercise training is an effective means of
      improving exercise capacity, thus improving ADL. Combination of repeated sauna
      therapy and exercise training may be recommended as a comprehensive treatment to
      improve cardiac function, ambulation capacity, and ADL in CHF patients.

PMID- 25941984
TI  - Molecular Analyses of Pyruvate Kinase Deficient Turkish Patients from a Single
      Center.
AB  - Erythrocyte pyruvate kinase deficiency is one of the most common causes of
      hereditary non-spherocytic hemolytic anemias. We investigated molecular
      alterations responsible for erythrocyte pyruvate kinase enzyme deficiency in four
      patients of the three unrelated Turkish families available from the pool of 12
      patients diagnosed as having pyruvate kinase deficiency in one center. One novel
      missense mutation located at cDNA nt 1623 G->C (Lys541Asn), and three previously
      described mutations at 1456 C->T (Arg486Trp), 1528 C->T (Arg510End), and 1675 C
      >G (Arg559Gly) were found to be associated with erythrocyte pyruvate kinase
      deficiency. All four mutations affect the C-domain of the protein. The three
      missense mutations result in amino acid changes, which cause an alteration in
      interaction between subunits by changing the local distribution of charges or by
      local conformational change on protein structure. The Arg510End mutation causes a
      deletion of terminal residues of the pyruvate kinase affecting the integrity of
      protein. This study presents the results of first molecular study on pyruvate
      kinase deficiency in Turkey. 

PMID- 25941986
TI  - [Why Psychotherapy Research should and can be Expanded in Germany].

PMID- 25941985
TI  - Camptothecin suppresses expression of matrix metalloproteinase-9 and vascular
      endothelial growth factor in DU145 cells through PI3K/Akt-mediated inhibition of
      NF-kappaB activity and Nrf2-dependent induction of HO-1 expression.
AB  - Though camptothecin (CPT) possesses potent anti-inflammatory, immunomodulatory,
      anticancerous, and antiproliferative effects, little is known about the mechanism
      by which CPT regulates the expression of matrix metalloproteinase-9 (MMP-9) and
      vascular endothelial growth factor (VEGF). Therefore, the current study aimed to
      investigate the effects of CPT on the expression of MMP-9 and VEGF, which are
      important factors for the invasion of tumors. In vitro application of CPT
      resulted in a slight inhibition of cell proliferation and a significant reduction
      in the matrigel invasion of DU145 cells. Treatment with CPT also downregulated
      phorbol-12-myristate-13-acetate (PMA)- and tumor necrosis factor-alpha (TNF
      alpha)-induced MMP-9 and VEGF expression by inhibiting nuclear factor-kappaB (NF
      kappaB) activity. Downregulation of phosphoinositide 3-kinase (PI3K)/Akt
      phosphorylation in response to CPT was revealed as an upstream pathway regulating
      the expression of MMP-9 and VEGF accompanying the inhibition of NF-kappaB
      activity. We further confirmed that CPT inhibits PMA-induced MMP-9 and VEGF
      expression by upregulating nuclear factor-erythroid related factor-2 (Nrf2)
      mediated heme oxygenase-1 (HO-1) induction. Taken together, these data indicate
      that CPT inhibits the invasion of cancer cells accompanied by suppression of MMP
      9 and VEGF production by suppressing the PI3K/Akt-mediated NF-kappaB pathway and
      enhancing the Nrf2-dependent HO-1 pathway, suggesting that CPT may be a good
      candidate to inhibit MMP-9 and VEGF expression. 

PMID- 25941987
TI  - [Agreement between Clinical Evaluation and Structured Clinical Interviews in
      Psychosomatic Inpatients].
AB  - The goal of this study was to determine the agreement between axis I mental
      disorders assessed with a structured clinical interview (SCID) and independently
      obtained non-structured clinical diagnoses in 185 psychosomatic in-patients.
      Additionally, the study focuses on the detection of potential predictors for the
      level of agreement. Diagnostic agreement was poor to moderate for the mood,
      anxiety and somatoform disorder cluster (kappa = 0.293-0.444). Only for eating
      disorders an almost complete concordance could be found (kappa = 0.812). The
      predictor analysis indicated a significant positive association between the
      comorbidity rate and the agreement in mood disorders. Furthermore, the diagnostic
      agreement of anxiety disorders was significantly higher for female than for male
      patients. These results reveal that even a team-based clinical diagnosis,
      assessed over the period of a hospital stay, shows little agreement with SCID
      diagnoses. The predictor analysis as well as the poor correlation in 3 of 4
      diagnostic clusters suggest that conceptual differences of the disorder criteria
      as well as their clinical interpretation might influence the concordance between
      diagnoses. Further studies focusing on methodical factors might reveal further
      insights to the cause of the diagnostic discrepancies.

PMID- 25941988
TI  - [From stand-alone solution to longitudinal communication curriculum--development
      and implementation at the Faculty of Medicine in Heidelberg].
AB  - At the Faculty of Medicine in Heidelberg, implementation of an interdisciplinary
      longitudinal curriculum was started in 2001 with the goal of achieving sustained
      promotion of communicative and clinical competences. The aim of this paper is to
      describe the development and implementation of Heidelberg's longitudinal
      communication curriculum. Furthermore, innovative aspects and strategies are
      discussed. The methodological approaches for development and implementation were
      Kern's "Six-step Approach" and a SWOT analysis. The process resulted in an
      innovative communication curriculum that starts with an integrated curriculum for
      developing clinical and communicative competence in the pre-clinical phase and
      continues in the clinical phase with medical communication and interactive
      training. Satisfaction with the communication curriculum and its effectiveness
      were rated highly by students. Residents who had graduated from Faculty of
      Medicine in Heidelberg rated the extent to which they had communicative
      competencies at the time of their graduation at their disposal significantly
      higher than residents who had graduated from the other 4 medical faculties in
      Baden-Wurttemberg. The experiences gained in Heidelberg can be applied by other
      faculties. 

PMID- 25941989
TI  - [Obituary: Gerhard Klumbies (5.12.1919-19.1.2015)--a pioneer of psychosomatic
      medicine in Germany].

PMID- 25941990
TI  - Nanomedicine approaches for corneal diseases.
AB  - Corneal diseases are the third leading cause of blindness globally. Topical
      nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, antibiotics and tissue
      transplantation are currently used to treat corneal pathological conditions.
      However, barrier properties of the ocular surface necessitate high concentration
      of the drugs applied in the eye repeatedly. This often results in poor efficacy
      and several side-effects. Nanoparticle-based molecular medicine seeks to overcome
      these limitations by enhancing the permeability and pharmacological properties of
      the drugs. The promise of nanomedicine approaches for treating corneal defects
      and restoring vision without side effects in preclinical animal studies has been
      demonstrated. Numerous polymeric, metallic and hybrid nanoparticles capable of
      transporting genes into desired corneal cells to intercept pathologic pathways
      and processes leading to blindness have been identified. This review provides an
      overview of corneal diseases, nanovector properties and their applications in
      drug-delivery and corneal disease management. 

PMID- 25941991
TI  - 25-hydroxyvitamin D levels, vitamin D binding protein gene polymorphisms and
      incident coronary heart disease among whites and blacks: The ARIC study.
AB  - BACKGROUND: In observational studies, low 25-hydroxyvitamin D (25(OH)D) has been
      associated with increased risk of coronary heart disease (CHD), and this
      association may vary by race. Racial differences in the frequency of vitamin D
      binding protein (DBP) single nucleotide polymorphisms (SNPs) might account for
      similar bioavailable vitamin D in blacks despite lower mean 25(OH)D. We
      hypothesized that the associations of low 25(OH)D with CHD risk would be stronger
      among whites and among persons with genotypes associated with higher DBP levels.
      METHODS: We measured 25(OH)D by mass spectroscopy in 11,945 participants in the
      ARIC Study (baseline 1990-1992, mean age 57 years, 59% women, 24% black). Two DBP
      SNPs (rs7041; rs4588) were genotyped. We used adjusted Cox proportional hazards
      models to examine the association of 25(OH)D with adjudicated CHD events through
      December 2011. RESULTS: Over a median of 20 years, there were 1230 incident CHD
      events. Whites in the lowest quintile of 25(OH)D (<17 ng/ml) compared to the
      upper 4 quintiles had an increased risk of incident CHD (HR 1.28, 95% CI 1.05
      1.56), but blacks did not (1.03, 0.82-1.28), after adjustment for demographics
      and behavioral/socioeconomic factors (p-interaction with race = 0.22). Results
      among whites were no longer significant after further adjustment for potential
      mediators of this association (i.e. diabetes, hypertension). There was no
      statistically significant interaction of 25(OH)D with the DBP SNPs rs4588 (p =
      0.92) or rs7041 (p = 0.87) in relation to CHD risk. CONCLUSIONS: Low 25(OH)D was
      associated with incident CHD in whites, but no interactions of 25(OH)D with key
      DBP genotypes was found.

PMID- 25941992
TI  - The neuron-derived orphan receptor 1 (NOR1) is induced upon human alternative
      macrophage polarization and stimulates the expression of markers of the M2
      phenotype.
AB  - BACKGROUND: Atherosclerosis is an inflammatory disease in which macrophages play
      a crucial role. Macrophages are present in different phenotypes, with at the
      extremes of the spectrum the classical M1 pro-inflammatory and the alternative M2
      anti-inflammatory macrophages. The neuron-derived orphan receptor 1 (NOR1),
      together with Nur77 and Nurr1, are members of the NR4A orphan nuclear receptor
      family, expressed in human atherosclerotic lesion macrophages. However, the role
      of NOR1 in human macrophages has not been studied yet. OBJECTIVES: To determine
      the expression and the functions of NOR1 in human alternative macrophages.
      METHODS AND RESULTS: In vitro IL-4 polarization of primary monocytes into
      alternative M2 macrophages enhances NOR1 expression in human but not in mouse
      macrophages. Moreover, NOR1 expression is most abundant in CD68+MR+ alternative
      macrophage-enriched areas of human atherosclerotic plaques in vivo. Silencing
      NOR1 in human alternative macrophages decreases the expression of several M2
      markers such as the Mannose Receptor (MR), Interleukin-1 Receptor antagonist (IL
      1Ra), CD200 Receptor (CD200R), coagulation factor XIII A1 polypeptide (F13A1),
      Interleukin 10 (IL-10) and the Peroxisome Proliferator-Activated Receptor
      (PPAR)gamma. Bioinformatical analysis identified F13A1, IL-1Ra, IL-10 and the
      Matrix Metalloproteinase-9 (MMP9) as potential target genes of NOR1 in human
      alternative macrophages. Moreover, expression and enzymatic activity of MMP9 are
      induced by silencing and repressed by NOR1 overexpression in M2 macrophages.
      CONCLUSIONS: These data identify NOR1 as a transcription factor induced during
      alternative differentiation of human macrophages and demonstrate that NOR1
      modifies the alternative macrophage phenotype.

PMID- 25941993
TI  - Fitting WWP-1 in the dietary restriction network.

PMID- 25941995
TI  - A randomized controlled trial of custom foot orthoses for the treatment of
      plantar heel pain.
AB  - BACKGROUND: Up to 10% of people will experience heel pain. The purpose of this
      prospective, double-blind, randomized clinical trial was to compare custom foot
      orthoses (CFO), prefabricated foot orthoses (PFO), and sham insole treatment for
      plantar fasciitis. METHODS: Seventy-seven patients with plantar fasciitis for
      less than 1 year were included. Outcome measures included first step and end of
      day pain, Revised Foot Function Index short form (FFI-R), 36-Item Short Form
      Health Survey (SF-36), activity monitoring, balance, and gait analysis. RESULTS:
      The CFO group had significantly improved total FFI-R scores (77.4 versus 57.2; P
      = .03) without group differences for FFI-R pain, SF-36, and morning or evening
      pain. The PFO and CFO groups reported significantly lower morning and evening
      pain. For activity, the CFO group demonstrated significantly longer episodes of
      walking over the sham (P = .019) and PFO (P = .03) groups, with a 125% increase
      for CFOs, 22% PFOs, and 0.2% sham. Postural transition duration (P = .02) and
      balance (P = .05) improved for the CFO group. There were no gait differences. The
      CFO group reported significantly less stretching and ice use at 3 months.
      CONCLUSIONS: The CFO group demonstrated 5.6-fold greater improvements in
      spontaneous physical activity versus the PFO and sham groups. All three groups
      improved in morning pain after treatment that included standardized athletic
      shoes, stretching, and ice. The CFO changes may have been moderated by decreased
      stretching and ice use after 3 months. These findings suggest that more objective
      measures, such as spontaneous physical activity improvement, may be more
      sensitive and specific for detecting improved weightbearing function than
      traditional clinical outcome measures, such as pain and disease-specific quality
      of life.

PMID- 25941994
TI  - Disruption of BRD4 at H3K27Ac-enriched enhancer region correlates with decreased
      c-Myc expression in Merkel cell carcinoma.
AB  - Pathologic c-Myc expression is frequently detected in human cancers, including
      Merkel cell carcinoma (MCC), an aggressive skin cancer with no cure for
      metastatic disease. Bromodomain protein 4 (BRD4) regulates gene transcription by
      binding to acetylated histone H3 lysine 27 (H3K27Ac) on the chromatin. Super
      enhancers of transcription are identified by enrichment of H3K27Ac. BET inhibitor
      JQ1 disrupts BRD4 association with super-enhancers, downregulates proto
      oncogenes, such as c-Myc, and displays antitumor activity in preclinical animal
      models of human cancers. Here we show that an enhancer proximal to the c-Myc
      promoter is enriched in H3K27Ac and associated with high occupancy of BRD4, and
      coincides with a putative c-Myc super-enhancer in MCC cells. This observation is
      mirrored in tumors from MCC patients. Importantly, depleted BRD4 occupancy at the
      putative c-Myc super-enhancer region by JQ1 correlates with decreased c-Myc
      expression. Thus, our study provides initial evidence that super-enhancers
      regulate c-Myc expression in MCC. 

PMID- 25941996
TI  - Efficient in vivo transfection and safety profile of a CpG-free and codon
      optimized luciferase plasmid using a cationic lipophosphoramidate in a multiple
      intravenous administration procedure.
AB  - As any drug, the success of gene therapy is largely dependent on the vehicle that
      has to selectively and efficiently deliver therapeutic nucleic acids into
      targeted cells with minimal side-effects. In the case of chronic diseases that
      require a life-long treatment, non-viral gene delivery vehicles are less likely
      to induce an immune response, thereby allowing for repeated administration.
      Beyond the gene delivery efficiency of a given vector, the nature of nucleic acid
      constructs also has a central importance in gene therapy protocols. Herein, we
      investigated the impact of two firefly luciferase encoding plasmids on the
      transgene expression profile following systemic delivery of lipoplexes in mice,
      as well as their potential to be safely and efficiently readministered. Whereas
      pTG11033 plasmid is driven by a strong ubiquitous cytomegalovirus promoter,
      pGM144 plasmid, which has been designed to avoid inflammation and provide
      sustained transgene expression in lungs, is CpG-free and is under control of the
      human elongation factor-1 alpha promoter. Combined to the efficient cationic
      lipophosphoramidate BSV4, bioluminescence data showed that both plasmids were
      mostly expressed in the lungs of mice following a primary injection of
      lipoplexes. However, mice transfected with pGM144 exhibited a higher and more
      sustained transgene expression than those treated with pTG11033. Repeated
      administration studies revealed that several injections of lipoplexes could lead
      to similar transgene expression profiles if an interval of several weeks between
      subsequent injections was respected. A transient hepatotoxicity and a partial
      inflammatory response were caused by lipoplex injection, irrespective of the
      plasmid used. Altogether, these results indicate that repeated systemic
      administration of lipophosphoramidate-based lipoplexes in mice conducts to an
      effective lung transfection without serious side effects, and highlight the need
      to use long-lasting expressing and well tolerated plasmids in order to
      efficiently renew transgene expression by the successive doses. 

PMID- 25941997
TI  - Generation of nanovesicles with sliced cellular membrane fragments for exogenous
      material delivery.
AB  - We propose a microfluidic system that generates nanovesicles (NVs) by slicing
      living cell membrane with microfabricated 500 nm-thick silicon nitride (SixNy)
      blades. Living cells were sliced by the blades while flowing through
      microchannels lined with the blades. Plasma membrane fragments sliced from the
      cells self-assembled into spherical NVs of ~100-300 nm in diameter. During self
      assembly, the plasma membrane fragments enveloped exogenous materials (here,
      polystyrene latex beads) from the buffer solution. About 30% of beads were
      encapsulated in NVs, and the generated NVs delivered the encapsulated beads
      across the plasma membrane of recipient cells, but bare beads could not penetrate
      the plasma membrane of recipient cells. This result implicates that the NVs
      generated using the method in this study can encapsulate and deliver exogenous
      materials to recipient cells, whereas exosomes secreted by cells can deliver only
      endogenous cellular materials.

PMID- 25941998
TI  - Simultaneously targeted imaging cytoplasm and nucleus in living cell by
      biomolecules capped ultra-small GdOF nanocrystals.
AB  - Simultaneously targeted imaging cytoplasm and nucleus in living cell by just one
      photoluminescent nanocrystals has been a giant challenge in nanobiotechnology and
      nanomedicine. Herein we report a novel Arg-Gly-Asp peptide (RGD) or cysteine
      (Cys) functionalized ultra-small GdOF nanocrystals for simultaneously targeted
      imaging cell cytoplasm and nucleus. As-prepared RGD@GdOF and Cys@GdOF
      nanocrystals possessed high water dispersibility, ultra-small size (about 5 nm)
      and double emissions (545 nm and 587 nm) with high quantum yield. Such
      functionalized nanocrystals presented high cellular biocompatibility and were
      successfully used to label living cells with very high signal to noise ratio. The
      living cells cytoplasm and nucleus (cancer cells and stem cells) could be imaged
      simultaneously through the mergence of green and red emission of nanocrystals,
      based on mechanism of fluorescent intensity difference. These functionalized
      nanocrystals also exhibited significantly higher photostability and brightness as
      compared to dyes. Such the ultra-small size, high photostability and intensity,
      double emissions, excellent biocompatibility and targeted ability, make as
      prepared functionalized nanocrystals particularly promising for cellular and
      molecular-level bioimaging applications.

PMID- 25941999
TI  - Biosorption of Cr(VI) ions from aqueous solutions by a newly isolated Bosea sp.
      strain Zer-1 from soil samples of a refuse processing plant.
AB  - The adsorption behavior of Cr(VI) ions from aqueous solution by a chromium
      tolerant strain was studied through batch experiments. An isolate designated Zer
      1 was identified as a species of Bosea on the basis of 16S rRNA results. It
      showed a maximum resistance to 550 mg.L(-1) Cr(VI). The effects of 3 important
      operating parameters, initial solution pH, initial Cr(VI) concentration, and
      biomass dose, were investigated by central composite design. On the basis of
      response surface methodology results, maximal removal efficiency of Cr(VI) was
      achieved under the following conditions: pH, 2.0; initial concentration of metal
      ions, 55 mg.L(-1); and biomass dose, 2.0 g.L(-1). Under the optimal conditions,
      the maximum removal efficiency of Cr(VI) ions was found to be nearly 98%. The
      experimental data exhibited a better fit with the Langmuir model than the
      Freundlich model. The biosorption mechanisms were investigated with pseudo-first
      order, pseudo-second-order, and intraparticle diffusion kinetics models. These
      results revealed that biosorption of Cr(VI) onto bacterial biomass could be an
      alternative method for the removal of metal ions from aqueous solution. 

PMID- 25942001
TI  - Solvent-Dependent Pyranopterin Cyclization in Molybdenum Cofactor Model
      Complexes.
AB  - The conserved pterin dithiolene ligand that coordinates molybdenum (Mo) in the
      cofactor (Moco) of mononuclear Mo enzymes can exist in both a tricyclic
      pyranopterin dithiolene form and as a bicyclic pterin-dithiolene form as observed
      in protein crystal structures of several bacterial molybdoenzymes.
      Interconversion between the tricyclic and bicyclic forms via pyran scission and
      cyclization has been hypothesized to play a role in the catalytic mechanism of
      Moco. Therefore, understanding the interconversion between the tricyclic and
      bicyclic forms, a type of ring-chain tautomerism, is an important aspect of study
      to understand its role in catalysis. In this study, equilibrium constants (K(eq))
      as well as enthalpy, entropy, and free energy values are obtained for pyran ring
      tautomerism exhibited by two Moco model complexes, namely,
      (Et4N)[Tp*Mo(O)(S2BMOPP)] (1) and (Et4N)[Tp*Mo(O)(S2PEOPP)] (2), as a solvent
      dependent equilibrium process. Keq values obtained from (1)H NMR data in seven
      deuterated solvents show a correlation between solvent polarity and tautomer
      form, where solvents with higher polarity parameters favor the pyran form.

PMID- 25942002
TI  - Pharmacokinetics of Inhaled Rifampicin Porous Particles for Tuberculosis
      Treatment: Insight into Rifampicin Absorption from the Lungs of Guinea Pigs.
AB  - Tuberculosis (TB) is a life-threatening infection that requires a lengthy
      treatment process that is often associated with adverse effects. Pulmonary
      delivery of anti-TB drugs has the potential to increase efficacy of treatment by
      increasing drug concentrations at the lungs, the primary site of infection. The
      aim of the present study is to evaluate the disposition of rifampicin (RIF) after
      its pulmonary administration as porous particles (PPs) to guinea pigs and
      contrast it to that after oral administration. RIF microparticles were prepared
      by spray drying a solution of RIF and L-leucine (9:1), and the resulting
      particles were characterized for their physicochemical properties. Animals
      received RIF either as intravenous solution (iv), as oral suspension of
      micronized RIF (ORS) and RIF-PPs (ORPP), or by insufflation of the PPs (IRPP).
      Plasma samples were collected at preselected time points, and bronchoalveolar
      lavage (BAL) was performed at the end of the study. RIF concentrations in
      biological samples were analyzed by HPLC. Plasma concentration versus time data
      was analyzed by compartmental and noncompartmental methods. RIF PPs were thin
      walled porous particles with mass median aerodynamic diameter (MMAD) of 4.8+/-0.1
      MUm, GSD=1.29+/-0.03, and fine particle fraction below 5.8 MUm of 52.9+/-2.0%.
      RIF content in the resulting particles was 91.8+/-0.1%. Plasma concentration vs
      time profiles revealed that the terminal slope of the iv group was different from
      that of the oral or pulmonary groups, indicating the possibility of flip-flop
      kinetics. RIF from IRPP appeared to be absorbed faster than that of ORPP or ORS
      as evidenced by higher RIF plasma concentrations up until 2 h. Notably, similar
      AUC (when corrected by dose), similar CL, lambda, and half-life were obtained
      after oral administration of RIF at 40 mg/kg and pulmonary administration of RIF
      at 20 mg/kg. However, RIF in the IRPP group had a shorter Tmax and higher
      bioavailability than orally dosed groups. In addition, RIF concentrations in the
      BAL of animals in the IRPP group were 3-4-fold larger than those in the orally
      dosed groups. The disposition in ORS and ORPP were best described by a model with
      two sequential compartments, whereas the disposition of IRPP was best described
      by a two parallel compartment model. The advantages of delivering RIF by the
      pulmonary route are demonstrated in the present study. These include achieving
      higher RIF concentrations in the lungs and similar systemic levels after
      pulmonary delivery of one-half of the oral nominal dose. This is expected to
      result in a more effective treatment of pulmonary TB, as shown previously in
      published efficacy studies.

PMID- 25942003
TI  - Optimization of carvacrol, rosmarinic, oleanolic and ursolic acid extraction from
      oregano herbs (Origanum onites L., Origanum vulgare spp. hirtum and Origanum
      vulgare L.).
AB  - The aim of our study was to increase the extraction efficiency of carvacrol,
      rosmarinic, oleanolic and ursolic acid from the different species of oregano
      herbs (Origanum onites L., Origanum vulgare spp. hirtum and Origanum vulgare L.).
      Various extraction methods (ultrasound-assisted, heat-reflux, continuous
      stirring, maceration, percolation) and extraction conditions (different solvent,
      material:solvent ratio, extraction temperature, extraction time) were used, and
      the active substances were determined by HPLC. The lowest content of carvacrol,
      rosmarinic, oleanolic and ursolic acid was obtained by percolation. During heat
      reflux extraction, the content of active substances depended on the solvent used:
      ethanol/non-aqueous solvent (glycerol or propylene glycol) mixture was more
      effective compared with ethanol alone. The results showed that for each species
      of oregano the most optimal extraction method should be selected to maximize the
      content of biologically active substances in the extracts. 

PMID- 25942005
TI  - Long-Term Services and Supports for Older Adults: A Review of Home and Community
      Based Services Versus Institutional Care.
AB  - Despite a shift from institutional services toward more home and community-based
      services (HCBS) for older adults who need long-term services and supports (LTSS),
      the effects of HCBS have yet to be adequately synthesized in the literature. This
      review of literature from 1995 to 2012 compares the outcome trajectories of older
      adults served through HCBS (including assisted living [AL]) and in nursing homes
      (NHs) for physical function, cognition, mental health, mortality, use of acute
      care, and associated harms (e.g., accidents, abuse, and neglect) and costs. NH
      and AL residents did not differ in physical function, cognition, mental health,
      and mortality outcomes. The differences in harms between HCBS recipients and NH
      residents were mixed. Evidence was insufficient for cost comparisons. More and
      better research is needed to draw robust conclusions about how the service
      setting influences the outcomes and costs of LTSS for older adults. Future
      research should address the numerous methodological challenges present in this
      field of research and should emphasize studies evaluating the effectiveness of
      HCBS. 

PMID- 25942004
TI  - Ultra-high density intra-specific genetic linkage maps accelerate identification
      of functionally relevant molecular tags governing important agronomic traits in
      chickpea.
AB  - We discovered 26785 and 16573 high-quality SNPs differentiating two parental
      genotypes of a RIL mapping population using reference desi and kabuli genome
      based GBS assay. Of these, 3625 and 2177 SNPs have been integrated into eight
      desi and kabuli chromosomes, respectively in order to construct ultra-high
      density (0.20-0.37 cM) intra-specific chickpea genetic linkage maps. One of these
      constructed high-resolution genetic map has potential to identify 33 major
      genomic regions harbouring 35 robust QTLs (PVE: 17.9-39.7%) associated with three
      agronomic traits, which were mapped within <1 cM mean marker intervals on desi
      chromosomes. The extended LD (linkage disequilibrium) decay (~15 cM) in
      chromosomes of genetic maps have encouraged us to use a rapid integrated approach
      (comparative QTL mapping, QTL-region specific haplotype/LD-based trait
      association analysis, expression profiling and gene haplotype-based association
      mapping) rather than a traditional QTL map-based cloning method to narrow-down
      one major seed weight (SW) robust QTL region. It delineated favourable natural
      allelic variants and superior haplotype-containing one seed-specific candidate
      embryo defective gene regulating SW in chickpea. The ultra-high-resolution
      genetic maps, QTLs/genes and alleles/haplotypes-related genomic information
      generated and integrated strategy for rapid QTL/gene identification developed
      have potential to expedite genomics-assisted breeding applications in crop
      plants, including chickpea for their genetic enhancement. 

PMID- 25942006
TI  - The ecology of pelagic freshwater methylotrophs assessed by a high-resolution
      monitoring and isolation campaign.
AB  - Methylotrophic planktonic bacteria fulfill a particular role in the carbon cycle
      of lakes via the turnover of single-carbon compounds. We studied two planktonic
      freshwater lineages (LD28 and PRD01a001B) affiliated with Methylophilaceae
      (Betaproteobacteria) in Lake Zurich, Switzerland, by a combination of molecular
      and cultivation-based approaches. Their spatio-temporal distribution was
      monitored at high resolution (n=992 samples) for 4 consecutive years. LD28
      methylotrophs constituted up to 11 * 10(7) cells l(-1) with pronounced peaks in
      spring and autumn-winter, concomitant with blooms of primary producers. They were
      rare in the warm water layers during summer but abundant in the cold hypolimnion,
      hinting at psychrophilic growth. Members of the PRD01a001B lineage were generally
      less abundant but also had maxima in spring. More than 120 axenic strains from
      these so far uncultivated lineages were isolated from the pelagic zone by
      dilution to extinction. Phylogenetic analysis separated isolates into two
      distinct genotypes. Isolates grew slowly (MUmax=0.4 d(-1)), were of conspicuously
      small size, and were indeed psychrophilic, with higher growth yield at low
      temperatures. Growth was enhanced upon addition of methanol and methylamine to
      sterile lake water. Genomic analyses of two strains confirmed a methylotrophic
      lifestyle with a reduced set of genes involved in C1 metabolism. The very small
      and streamlined genomes (1.36 and 1.75 Mb) shared several pathways with the
      marine OM43 lineage. As the closest described taxa (Methylotenera sp.) are only
      distantly related to either set of isolates, we propose a new genus with two
      species, that is, 'Candidatus Methylopumilus planktonicus' (LD28) and 'Candidatus
      Methylopumilus turicensis' (PRD01a001B). 

PMID- 25942008
TI  - Screening and Treating UN Peacekeepers to Prevent the Introduction of Artemisinin
      Resistant Malaria into Africa.

PMID- 25942007
TI  - mTORC1 Regulates Flagellin-Induced Inflammatory Response in Macrophages.
AB  - Bacterial flagellin triggers inflammatory responses. Phosphoinositide 3-kinase
      (PI3K) and mammalian target of rapamycin (mTOR) regulate the production of pro-
      and anti-inflammatory cytokines that are induced by extrinsic antigens, but the
      function of mTORC1 in flagellin-induced inflammatory response is unknown. The
      purpose of this study was to examine the role and the mechanism of PI3K/Akt/mTOR
      pathway in flagellin-induced cytokine expression in mouse macrophages. We
      observed that flagellin upregulated TNF-alpha time- and dose-dependently.
      Flagellin stimulated rapid (<15 min) PI3K/Akt/mTOR phosphorylation that was
      mediated by TLR5. Inhibition of PI3K with LY294002 and wortmannin, and of mTORC1
      with rapamycin decreased flagellin-induced TNF-alpha and IL-6 expression and cell
      proliferation. The activation of NF-kappaB p65 and STAT3 was regulated by mTORC1
      via degradation of IkappaBalpha and phosphorylation of STAT3 in response to
      flagellin, respectively. Thus, the PI3K/Akt/mTORC1 pathway regulates the innate
      immune response to bacterial flagellin. Rapamycin is potential therapy that can
      regulate host defense against pathogenic infections. 

PMID- 25942009
TI  - Years of Life Lost (YLL) in Colombia 1998-2011: Overall and Avoidable Causes of
      Death Analysis.
AB  - OBJECTIVE: Estimate the Years of Life Lost (YLL) for overall and avoidable causes
      of death (CoD) in Colombia for the period 1998-2011. METHODS: From the reported
      deaths to the Colombian mortality database during 1998-2011, we classified deaths
      from avoidable causes. With the reference life table of the Global Burden of
      Disease (GBD) 2010 study, we estimated the overall YLL and YLL due to avoidable
      causes. Calculations were performed with the difference between life expectancy
      and the age of death. Results are reported by group of cause of death, events,
      sex, year and department. Comparative analysis between number of deaths and YLL
      was carried out. RESULTS: A total of 83,856,080 YLL were calculated in Colombia
      during period 1998-2011, 75.9% of them due to avoidable CoD. The year 2000
      reported the highest number of missed YLL by both overall and avoidable CoD. The
      departments with the highest YLL rates were Caqueta, Guaviare, Arauca, Meta, and
      Risaralda. In men, intentional injuries and cardiovascular and circulatory
      diseases had the higher losses, while in women YLL were mainly due to
      cardiovascular and circulatory diseases. CONCLUSIONS: The public health
      priorities should focus on preventing the loss of YLL due to premature death and
      differentiated interventions by sex.

PMID- 25942010
TI  - Dynamic impedance model of the skin-electrode interface for transcutaneous
      electrical stimulation.
AB  - Transcutaneous electrical stimulation can depolarize nerve or muscle cells
      applying impulses through electrodes attached on the skin. For these
      applications, the electrode-skin impedance is an important factor which
      influences effectiveness. Various models describe the interface using constant or
      current-depending resistive-capacitive equivalent circuit. Here, we develop a
      dynamic impedance model valid for a wide range stimulation intensities. The model
      considers electroporation and charge-dependent effects to describe the impedance
      variation, which allows to describe high-charge pulses. The parameters were
      adjusted based on rectangular, biphasic stimulation pulses generated by a
      stimulator, providing optionally current or voltage-controlled impulses, and
      applied through electrodes of different sizes. Both control methods deliver a
      different electrical field to the tissue, which is constant throughout the
      impulse duration for current-controlled mode or have a very current peak for
      voltage-controlled. The results show a predominant dependence in the current
      intensity in the case of both stimulation techniques that allows to keep a simple
      model. A verification simulation using the proposed dynamic model shows
      coefficient of determination of around 0.99 in both stimulation types. The
      presented method for fitting electrode-skin impedance can be simple extended to
      other stimulation waveforms and electrode configuration. Therefore, it can be
      embedded in optimization algorithms for designing electrical stimulation
      applications even for pulses with high charges and high current spikes. 

PMID- 25942011
TI  - Antihypertensive peptides of animal origin: A review.
AB  - Many bioactive peptides trigger certain useful antihypertensive activities in the
      living body system and there is a mounting worldwide interest in the therapeutic
      potential of these bioactive peptides for exploitation in vivo against the
      hypertension. Studies suggest the antihypertensive properties for many bioactive
      peptides of animal origin with underlying mechanisms ranging from inhibition of
      angiotensin-converting enzyme to additional mechanisms to lower blood pressure
      such as opioid-like activities and mineral-binding and antithrombotic properties.
      Antihypertensive peptides are the most extensively studied of all the
      bioactivities induced by food protein hydrolysates, highlighting their importance
      in human health and disease prevention and treatment. There exist enormous
      opportunities for the production of novel peptide-based products in
      biopharmaceutical manufacturing industries for the treatment, prevention, and
      mitigation of hypertension. Numerous products have already struck on the global
      market and many more are in process. This article focuses on antihypertensive
      peptides identified in the meat, fish, blood, milk, dairy products, and egg and
      their probable application as novel ingredients in the development of functional
      food products as dietary treatment of hypertension.

PMID- 25942012
TI  - The effect of high-intensity circuit training on physical fitness.
AB  - BACKGROUND: The purpose of this study was to examine the effect of a high
      intensity circuit training regimen, using only body weight as resistance, on
      physical fitness. METHODS: Ninety-six recreationally active college aged subjects
      (53 female, 43 male) completed the study. Following baseline testing for height
      and weight, body composition, aerobic fitness, muscle strength and muscle
      endurance, subjects were randomly assigned to one of three groups: 7-minute
      circuit training (CT-7), 14-minute circuit training (CT-14), and a non-training
      control group (C). Subjects in the CT-7 group (females, N.=17; males, N.=15) were
      asked to complete a seven minute circuit training workout for eight weeks (three
      workouts per week). The CT-14 group (females, N.=15; males, N.=13) followed the
      same protocol as CT-7 through the first four weeks. For the second four weeks
      they increased exercise time to 14 minutes with the same 7 minute circuit
      performed twice consecutively. Subjects in group C (females, N.=21; males, N.=15)
      maintained their normal activity levels throughout the course of the study.
      RESULTS: There were no significant differences between the groups for any
      variables tested prior to the exercise intervention. A repeated measures analysis
      of variance revealed statistically significant improvements in muscular endurance
      (push-ups) for both male and female subjects in the CT-7 and CT-14 groups. Males
      in the two exercising groups also showed improvement in muscular strength while
      aerobic capacity increased for females in the CT-14 group. CONCLUSIONS: These
      results suggest that short duration, high intensity circuit training may improve
      muscle endurance in moderately fit populations. Slight improvements that are
      gender specific may also be observed in muscle strength as well as aerobic
      fitness.

PMID- 25942013
TI  - The association between plantar heel pain and running surfaces in competitive
      long-distance male runners.
AB  - BACKGROUND: Plantar heel pain (PHP) is a common complaint, and is most often
      caused by plantar fasciitis. Plantar fasciitis is reported to be associated with
      running surfaces, however the association between PHP and running surfaces has
      not previously been revealed in an epidemiological investigation. Therefore, the
      purpose of the current study was to examine the association between PHP and
      running surfaces. METHODS: This is a cross-sectional study. A total of 347
      competitive long-distance male runners participated in this study. The
      participants completed an original questionnaire, which included items assessing
      demographic characteristics, training characteristics focusing on running
      surfaces (soft surface, hard surface and tartan), and the prevalence of PHP
      during the previous 12 months. A logistic regression analysis was used to
      identify the effect of running surfaces on PHP. RESULTS: We found that 21.9% of
      participants had experienced PHP during the previous 12 months. The multivariate
      logistic regression analysis, after adjusting for demographic and training
      characteristics, revealed that running on tartan was associated with PHP (odds
      ratio 2.82, 95% confidence interval 1.42 to 5.61; P<0.01). CONCLUSIONS: Our
      findings suggest that running more than 25% on tartan is associated with PHP in
      competitive long-distance male runners.

PMID- 25942014
TI  - Effects of resistance exercise and the use of anabolic androgenic steroids on
      hemodynamic characteristics and muscle damage markers in bodybuilders.
AB  - BACKGROUND: Anabolic androgenic steroids (AAS), synthetic compounds of
      testosterone commonly used as sport performance enhancers, could cause
      cardiovascular dysfunction and cell damage. Even though the side effects of AAS
      intake have been widely studied, yet little is known about how resistance
      exercise can alter these side effects. This study aimed to determine the effects
      of one session resistance exercise and the use of AAS on hemodynamic
      characteristics and muscle damage markers in professional bodybuilders. METHODS:
      Sixteen bodybuilders were divided into two groups: bodybuilders using AAS for at
      least 5 years (users; N.=8) and AAS-free bodybuilders (non-users; N.=8). The
      exercise protocol was a circuit strength training session involved three sets of
      8-9 repetitions at 80-85% of 1-RM. Heart rate (HR), blood pressure (BP) and
      concentrations of serum creatine kinase (CK) and lactate dehydrogenase (LDH) were
      measured at three different time points, immediately before and after the
      exercise session and 24 hours following the exercise session. RESULTS: The users
      group showed greater basal levels of hemodynamic characteristics (i.e. HR and BP)
      and cell damage markers (i.e. CK and LDH) compared to those in the non-users
      group (all P<0.05). Furthermore, the exercise session significantly increased the
      levels of HR (P=0.02) and CK (P=0.01) in the users group compared to those in the
      non-users group immediately after the exercise. No significant differences were
      observed in BP and LDH responses to exercise between the users and the non-users
      groups (P>0.05). CONCLUSIONS: These findings indicate that the use of AAS could
      be potentially harmful as it enhances the levels of the hemodynamic
      characteristics and the muscle enzymes. These harmful effects of AAS intake could
      be more evident in response to resistance exercise.

PMID- 25942015
TI  - Acute effects of whole-body vibration on energy metabolism during aerobic
      exercise.
AB  - BACKGROUND: This study was undertaken to evaluate the effectiveness of preworkout
      whole-body vibration (WBV) in optimizing energy expenditure and substrate
      oxidation during subsequent aerobic exercise. METHODS: Nine male and seven female
      subjects underwent six sets of 10 body weight squats on a vibration platform with
      either no WBV (NV), 40-Hz WBV at lower amplitude (1-2 mm) (LV), or 40-Hz WBV at
      higher amplitude (2-3 mm) (HV) in a randomized order. Each WBV treatment was
      immediately followed by 20 min of constant-load cycle exercise at an intensity
      that elicited 65% VO2peak. Oxygen uptake (VO2) and carbon dioxide production
      (VCO2) were measured continuously during both the WBV treatment and the
      subsequent exercise. Heart rate (HR) was recorded at the end of each set of body
      weight squat during the vibration treatment and continuously during the
      subsequent exercise. Rates of carbohydrate (COX) and fat oxidation (FOX) were
      calculated based on VO2 and VCO2 using the stoichiometric equations. RESULTS:
      During the WBV treatment, VO2 in both l?min-1 and mL?kg-1?min-1 were higher
      (P<0.05) in HV than NV, while no differences in VO2 were seen between HV and LV
      and between LV and NV. These metabolic responses occurred similarly in both males
      and females. During subsequent exercise, VO2 was higher (P<0.05) in HV than NV at
      5th and 10th min of exercise. No between-trial differences in HR, COX, and FOX
      were observed during either the WBV treatment or the subsequent exercise.
      CONCLUSIONS: 40-Hz WBV at higher amplitude augments oxygen uptake, which persists
      through the early portion of aerobic exercise that commences immediately after
      WBV. The increased metabolic effect of WBV seems load-dependent as WVB with
      amplitude smaller than 2 mm did not elevate VO2 significantly. Men and women
      respond similarly to a vibratory stimulus despite the difference in body mass.

PMID- 25942016
TI  - Agility performance in high-level junior basketball players: the predictive value
      of anthropometrics and power qualities.
AB  - BACKGROUND: In basketball, anthropometric status is an important factor when
      identifying and selecting talents, while agility is one of the most vital motor
      performances. The aim of this investigation was to evaluate the influence of
      anthropometric variables and power capacities on different preplanned agility
      performances. METHODS: The participants were 92 high-level, junior-age basketball
      players (16-17 years of age; 187.6+/-8.72 cm in body height, 78.40+/-12.26 kg in
      body mass), randomly divided into a validation and cross-validation subsample.
      The predictors set consisted of 16 anthropometric variables, three tests of power
      capacities (Sargent-jump, broad-jump and medicine-ball-throw) as predictors. The
      criteria were three tests of agility: a T-Shape-Test; a Zig-Zag-Test, and a test
      of running with a 180-degree turn (T180). Forward stepwise multiple regressions
      were calculated for validation subsamples and then cross-validated. Cross
      validation included correlations between observed and predicted scores, dependent
      samples t-test between predicted and observed scores; and Bland Altman graphics.
      RESULTS: Analysis of the variance identified centres being advanced in most of
      the anthropometric indices, and medicine-ball-throw (all at P<0.05); with no
      significant between-position-differences for other studied motor performances.
      Multiple regression models originally calculated for the validation subsample
      were then cross-validated, and confirmed for Zig-zag-Test (R of 0.71 and 0.72 for
      the validation and cross-validation subsample, respectively). Anthropometrics
      were not strongly related to agility performance, but leg length is found to be
      negatively associated with performance in basketball-specific agility. Power
      capacities are confirmed to be an important factor in agility. CONCLUSIONS: The
      results highlighted the importance of sport-specific tests when studying pre
      planned agility performance in basketball. The improvement in power capacities
      will probably result in an improvement in agility in basketball athletes, while
      anthropometric indices should be used in order to identify those athletes who can
      achieve superior agility performance.

PMID- 25942017
TI  - A Novel Type II NAD+-Specific Isocitrate Dehydrogenase from the Marine Bacterium
      Congregibacter litoralis KT71.
AB  - In most living organisms, isocitrate dehydrogenases (IDHs) convert isocitrate
      into alpha-ketoglutarate (alpha-KG). Phylogenetic analyses divide the IDH protein
      family into two subgroups: types I and II. Based on cofactor usage, IDHs are
      either NAD+-specific (NAD-IDH) or NADP+-specific (NADP-IDH); NADP-IDH evolved
      from NAD-IDH. Type I IDHs include NAD-IDHs and NADP-IDHs; however, no type II NAD
      IDHs have been reported to date. This study reports a novel type II NAD-IDH from
      the marine bacterium Congregibacter litoralis KT71 (ClIDH, GenBank accession no.
      EAQ96042). His-tagged recombinant ClIDH was produced in Escherichia coli and
      purified; the recombinant enzyme was NAD+-specific and showed no detectable
      activity with NADP+. The Km values of the enzyme for NAD+ were 262.6+/-7.4 MUM or
      309.1+/-11.2 MUM with Mg2+ or Mn2+ as the divalent cation, respectively. The
      coenzyme specificity of a ClIDH Asp487Arg/Leu488His mutant was altered, and the
      preference of the mutant for NADP+ was approximately 24-fold higher than that for
      NAD+, suggesting that ClIDH is an NAD+-specific ancestral enzyme in the type II
      IDH subgroup. Gel filtration and analytical ultracentrifugation analyses revealed
      the homohexameric structure of ClIDH, which is the first IDH hexamer discovered
      thus far. A 163-amino acid segment of CIIDH is essential to maintain its
      polymerization structure and activity, as a truncated version lacking this region
      forms a non-functional monomer. ClIDH was dependent on divalent cations, the most
      effective being Mn2+. The maximal activity of purified recombinant ClIDH was
      achieved at 35 degrees C and pH 7.5, and a heat inactivation experiment showed
      that a 20-min incubation at 33 degrees C caused a 50% loss of ClIDH activity. The
      discovery of a NAD+-specific, type II IDH fills a gap in the current
      classification of IDHs, and sheds light on the evolution of type II IDHs. 

PMID- 25942018
TI  - Assessment of the quality of antenatal care services provided by health workers
      using a mobile phone decision support application in northern Nigeria: a pre/post
      intervention study.
AB  - BACKGROUND: Given the shortage of skilled healthcare providers in Nigeria,
      frontline community health extension workers (CHEWs) are commonly tasked with
      providing maternal and child health services at primary health centers. In 2012,
      we introduced a mobile case management and decision support application in twenty
      primary health centers in northern Nigeria, and conducted a pre-test/post-test
      study to assess whether the introduction of the app had an effect on the quality
      of antenatal care services provided by this lower-level cadre. METHODS: Using the
      CommCare mobile platform, the app dynamically guides CHEWs through antenatal care
      protocols and collects client data in real time. Thirteen health education audio
      clips are also embedded in the app for improving and standardizing client
      counseling. To detect changes in quality, we developed an evidence-based quality
      score consisting of 25 indicators, and conducted a total of 266 client exit
      interviews. We analyzed baseline and endline data to assess changes in the
      overall quality score as well as changes in the provision of key elements of
      antenatal care. RESULTS: Overall, the quality score increased from 13.3 at
      baseline to 17.2 at endline (p<0.0001), out of a total possible score of 25, with
      the most significant improvements related to health counseling, technical
      services provided, and quality of health education. CONCLUSION: These study
      results suggest that the introduction of a low-cost mobile case management and
      decision support application can spur behavior change and improve the quality of
      services provided by a lower level cadre of healthcare workers. Future research
      should employ a more rigorous experimental design to explore potential longer
      term effects on client health outcomes.

PMID- 25942020
TI  - Electronic structure of hole-conducting states in polyprolines.
AB  - Electron transfer over long distances in proteins by a hopping process requires
      transient relay stations that can harbor charge and spin for a short time span.
      Certain easily oxidizable or reducible side chains may assume that role, but it
      has been shown that charge transport in peptides can also take place in the
      absence of such groups which implies that the peptide backbone provides for
      hopping stations. We have identified three different types of radical cation
      states in such peptides that are associated with significantly lower ionization
      potentials than those of the constituent amino acids, and which may thus serve as
      relay stations for hole transport. Which of these states is the most stable one
      depends on the nature and the conformation of the peptide. In contrast to alpha
      helices which, due to their high dipole moments, can only form stable radical
      cation states that are localized on the C-terminal amino acids, polyprolines are
      capable of accommodating such states inside the PPII helices and those states may
      serve as relay stations for hole transfer through polyprolines. Of which type
      these states are depends often on small conformational changes, and sometimes the
      most stable states are hybrids of the three types we have identified. 

PMID- 25942019
TI  - The neural basis of testable and non-testable beliefs.
AB  - Beliefs about the state of the world are an important influence on both normal
      behavior and psychopathology. However, understanding of the neural basis of
      belief processing remains incomplete, and several aspects of belief processing
      have only recently been explored. Specifically, different types of beliefs may
      involve fundamentally different inferential processes and thus recruit distinct
      brain regions. Additionally, neural processing of truth and falsity may differ
      from processing of certainty and uncertainty. The purpose of this study was to
      investigate the neural underpinnings of assessment of testable and non-testable
      propositions in terms of truth or falsity and the level of certainty in a belief.
      Functional magnetic resonance imaging (fMRI) was used to study 14 adults while
      they rated propositions as true or false and also rated the level of certainty in
      their judgments. Each proposition was classified as testable or non-testable.
      Testable propositions activated the DLPFC and posterior cingulate cortex, while
      non-testable statements activated areas including inferior frontal gyrus,
      superior temporal gyrus, and an anterior region of the superior frontal gyrus. No
      areas were more active when a proposition was accepted, while the dorsal anterior
      cingulate was activated when a proposition was rejected. Regardless of whether a
      proposition was testable or not, certainty that the proposition was true or false
      activated a common network of regions including the medial prefrontal cortex,
      caudate, posterior cingulate, and a region of middle temporal gyrus near the
      temporo-parietal junction. Certainty in the truth or falsity of a non-testable
      proposition (a strong belief without empirical evidence) activated the insula.
      The results suggest that different brain regions contribute to the assessment of
      propositions based on the type of content, while a common network may mediate the
      influence of beliefs on motivation and behavior based on the level of certainty
      in the belief. 

PMID- 25942023
TI  - Cloning and chart similarity.

PMID- 25942022
TI  - How can dermatologists help dermatopathologists work "smarter" for them?

PMID- 25942021
TI  - Immobilization of Zidovudine Derivatives on the SBA-15 Mesoporous Silica and
      Evaluation of Their Cytotoxic Activity.
AB  - Novel zidovudine derivatives, able to be covalently conjugated to silica surface,
      have been obtained and grafted to SBA-15 mesoporous silica. Cytotoxic activity of
      the hybrid organic-inorganic (zidovudine derivatives-silica) systems against HeLa
      and KB cell lines has been analyzed. Addition of folic acid had a positive
      influence on the cytotoxicity. Up to 69% of HeLa and 65% of KB tumor cells growth
      inhibition has been achieved at low silica concentration used (10 MUg/mL). 

PMID- 25942024
TI  - Diagnosis and treatment of leprosy type 1 (reversal) reaction.
AB  - Leprosy is a chronic granulomatous infection caused by the organism Mycobacterium
      leprae that primarily affects the skin and peripheral nerves. Leprosy has several
      distinct clinical presentations ranging from moderate to severe, with the extent
      of disease generally depending on the host's immune response to the infection.
      Treatment typically involves antimicrobials (eg, clofazimine, dapsone, rifampin).
      Once treatment is started, an important aspect of patient care is the recognition
      of possible reversal reactions. We report the case of a 44-year-old man who
      repeatedly developed physical findings consistent with a type 1 (reversal)
      reaction after undergoing multiple treatments for leprosy. A discussion of
      leprosy along with its clinical manifestations, treatment methods, and management
      of reversal reactions also is provided. 

PMID- 25942025
TI  - Factors affecting the pursuit of academic careers among dermatology residents.
AB  - There is a shortage of academic dermatologists in the United States. This study
      aimed to examine characteristics of US dermatology residency programs that affect
      the odds of producing academic dermatologists. Data regarding program size,
      faculty, grants, alumni residency program attended, lectures, and publications
      for all accredited US dermatology residency programs were collected; these data
      were correlated with the ratio of graduating full-time faculty members to
      estimated total number of graduates for each respective program. Results
      emphasize that the ratio of faculty to residents and the number of full-time
      faculty publications may represent key factors by which residency programs can
      increase their graduation of academic dermatologists. 

PMID- 25942026
TI  - High-yield biopsy technique for subepidermal blisters.
AB  - Dermatologists often perform 2 biopsies in patients with widespread tense
      blisters: one for light microscopy and another for direct immunofluorescence
      (DIF). Biopsy techniques recommended for blistering diseases with tense blisters
      are discussed, and illustrations demonstrate an alternative approach utilizing a
      single punch biopsy. A single punch biopsy is more cost effective and provides
      the same diagnostic information as the standard 2-biopsy approach for
      subepidermal blisters plus additional salt-split skin-like diagnostic
      information. A limitation for bisecting the single punch biopsy specimen is a
      potential complete separation of the epidermis from the dermis. The single punch
      biopsy technique is a simple cost-effective method for obtaining necessary
      diagnostic information when sampling tense blisters in patients with blistering
      diseases. 

PMID- 25942027
TI  - Cholinergic urticaria with anaphylaxis: hazardous duty of a deployed US marine.
AB  - Cholinergic urticaria (CU) is triggered by a rise in body temperature and can be
      complicated by bronchial hyperresponsiveness and anaphylaxis. It primarily
      affects young adults who actively engage in strenuous exercise, such as
      servicemen and servicewomen. If the patient reports a history of wheezing or
      difficulty breathing with urticaria, a water challenge test in a warm bath can be
      performed to confirm the presence of anaphylaxis. The test should be conducted in
      an environment in which the patient's airway can be secured and epinephrine can
      be administered if necessary. Nonsedating antihistamines commonly are used to
      treat CU, but few other treatments have been thoroughly evaluated for cases that
      are refractory to antihistamines. We present the case of a 27-year-old US Marine
      with CU and anaphylaxis confirmed by a water challenge test in a warm bath. 

PMID- 25942028
TI  - Trichoepithelioma and spiradenoma collision tumor.

PMID- 25942029
TI  - Scalp hyperkeratosis in children with skin of color: diagnostic and therapeutic
      considerations.
AB  - Scalp hyperkeratosis is common in childhood and adolescence. Diagnosis is
      affected by age, race, and history of infectious exposure, and associated
      symptoms including atopic features, alopecia, inflammatory nodules, presence and
      type of cutaneous lesions outside of the scalp, and nuchal lymphadenopathy. Tinea
      capitis is common in children with skin of color, especially black and Hispanic
      children. In adolescents, seborrheic dermatitis predominates as the cause of
      scalp hyperkeratosis, but tinea is still of concern. This article aims to help
      the practitioner comfortably diagnose and treat scalp hyperkeratosis in children
      with skin of color. 

PMID- 25942030
TI  - What is your diagnosis? New World cutaneous leishmaniasis.

PMID- 25942031
TI  - Painful purpura and cutaneous necrosis.

PMID- 25942032
TI  - Fibrous forehead plaque.

PMID- 25942033
TI  - Pneumonic tularemia presenting with a vesicular eruption.

PMID- 25942034
TI  - Mucocutaneous presentation of Kaposi sarcoma in an asymptomatic human
      immunodeficiency virus-positive man.
AB  - Kaposi sarcoma (KS) is a malignant proliferation of endothelial cells within the
      skin. The clinical presentation is characterized by clusters of violaceous
      macules and papules that often appear on the distal extremities or trunk with or
      without oral mucosal involvement. Mucocutaneous lesions are present at onset of
      diagnosis in a minority of cases. The lesions can evolve to include the mucous
      membranes of the gastric mucosa and the lungs. We present a unique case of KS in
      a 45-year-old, asymptomatic, human immunodeficiency virus (HIV)-positive man with
      mucocutaneous involvement to highlight the importance of recognizing KS in
      immunocompromised patients. 

PMID- 25942035
TI  - Yoga for dermatologic conditions.
AB  - As both a dermatology resident and yoga instructor, I find the potential
      correlation between the 2 disciplines to be interesting and a growing topic of
      attention in the media today. With the rising trend of practicing yoga, which
      encompasses physical postures, breathing exercises, and meditation or
      mindfulness, it is inevitable that patients will inquire about the benefits of
      yoga in managing dermatologic problems. In this column, I will discuss the
      dermatologic manifestations of stress as well as the known health benefits of
      yoga as described in the literature so that residents may offer an objective
      opinion about yoga in response to patient inquiries. 

PMID- 25942036
TI  - Nodule on the second toe in an infant.

PMID- 25942037
TI  - Rapidly recurring keratoacanthoma.

PMID- 25942038
TI  - In vivo confocal microscopy in the diagnosis of onychomycosis.

PMID- 25942039
TI  - Effect of molecular diffusion on the spin dynamics of a micellized radical pair
      in low magnetic fields studied by Monte Carlo simulation.
AB  - Magnetic field effect is a powerful tool to study dynamics and kinetics of
      radical pairs (RPs), which are one of the most important intermediates for
      organic photon-energy conversion reactions. However, quantitative discussion
      regarding the relationship between the modulation of interelectron interactions
      and spin dynamics at low magnetic fields (<10 mT) is still an open question. We
      have studied the spin dynamics of a long-lived RP in a micelle by newly developed
      Monte Carlo simulation, in which fluctuations of the exchange and magnetic
      dipolar interactions by in-cage diffusion are directly introduced to the time
      domain spin dynamics calculation. State-dependent relaxation/dephasing times of a
      few to a few tens of nanoseconds are obtained by simulations without hyperfine
      interactions (HFIs) as a function of the mutual diffusion constant (~10(-6)
      cm(2)/s). Simulations with the HFIs exhibit incoherent singlet-triplet (S-T)
      mixings resulting from interplay between the HFIs and the fluctuating spin-spin
      interactions. The experimentally observed incoherent S-T mixing of ~20 ns at 3 mT
      for a singlet-born RP in a sodium dodecyl sulfate micelle is reproduced by the
      simulation with reasonable diffusion coefficients. The computational method
      developed here contributes to quantitative detection of molecular motion that
      governs the recombination efficiency of RPs. 

PMID- 25942040
TI  - Childhood trauma, midbrain activation and psychotic symptoms in borderline
      personality disorder.
AB  - Childhood trauma is believed to contribute to the development of borderline
      personality disorder (BPD), however the mechanism by which childhood trauma
      increases risk for specific symptoms of the disorder is not well understood.
      Here, we explore the relationship between childhood trauma, brain activation in
      response to emotional stimuli and psychotic symptoms in BPD. Twenty individuals
      with a diagnosis of BPD and 16 healthy controls were recruited to undergo a
      functional MRI scan, during which they viewed images of faces expressing the
      emotion of fear. Participants also completed the childhood trauma questionnaire
      (CTQ) and a structured clinical interview. Between-group differences in brain
      activation to fearful faces were limited to decreased activation in the BPD group
      in the right cuneus. However, within the BPD group, there was a significant
      positive correlation between physical abuse scores on the CTQ and BOLD signal in
      the midbrain, pulvinar and medial frontal gyrus to fearful (versus neutral)
      faces. In addition there was a significant correlation between midbrain
      activation and reported psychotic symptoms in the BPD group (P<0.05). These
      results show that physical abuse in childhood is, in individuals with BPD,
      associated with significantly increased activation of a network of brain regions
      including the midbrain in response to emotional stimuli. Sustained differences in
      the response of the midbrain to emotional stimuli in individuals with BPD who
      suffered childhood physical abuse may underlie the vulnerability of these
      patients to developing psychotic symptoms. 

PMID- 25942041
TI  - Effects of prenatal and postnatal depression, and maternal stroking, at the
      glucocorticoid receptor gene.
AB  - In animal models, prenatal and postnatal stress is associated with elevated
      hypothalamic-pituitary axis (HPA) reactivity mediated via altered glucocorticoid
      receptor (GR) gene expression. Postnatal tactile stimulation is associated with
      reduced HPA reactivity mediated via increased GR gene expression. In this first
      study in humans to examine the joint effects of prenatal and postnatal
      environmental exposures, we report that GR gene (NR3C1) 1-F promoter methylation
      in infants is elevated in the presence of increased maternal postnatal depression
      following low prenatal depression, and that this effect is reversed by self
      reported stroking of the infants by their mothers over the first weeks of life. 

PMID- 25942042
TI  - d-serine levels in Alzheimer's disease: implications for novel biomarker
      development.
AB  - Alzheimer's disease (AD) is a severe neurodegenerative disorder still in search
      of effective methods of diagnosis. Altered levels of the NMDA receptor co
      agonist, d-serine, have been associated with neurological disorders, including
      schizophrenia and epilepsy. However, whether d-serine levels are deregulated in
      AD remains elusive. Here, we first measured D-serine levels in post-mortem
      hippocampal and cortical samples from nondemented subjects (n=8) and AD patients
      (n=14). We next determined d-serine levels in experimental models of AD,
      including wild-type rats and mice that received intracerebroventricular
      injections of amyloid-beta oligomers, and APP/PS1 transgenic mice. Finally, we
      assessed d-serine levels in the cerebrospinal fluid (CSF) of 21 patients with a
      diagnosis of probable AD, as compared with patients with normal pressure
      hydrocephalus (n=9), major depression (n=9) and healthy controls (n=10), and
      results were contrasted with CSF amyloid-beta/tau AD biomarkers. d-serine levels
      were higher in the hippocampus and parietal cortex of AD patients than in control
      subjects. Levels of both d-serine and serine racemase, the enzyme responsible for
      d-serine production, were elevated in experimental models of AD. Significantly, d
      serine levels were higher in the CSF of probable AD patients than in non
      cognitively impaired subject groups. Combining d-serine levels to the amyloid/tau
      index remarkably increased the sensitivity and specificity of diagnosis of
      probable AD in our cohort. Our results show that increased brain and CSF d-serine
      levels are associated with AD. CSF d-serine levels discriminated between
      nondemented and AD patients in our cohort and might constitute a novel candidate
      biomarker for early AD diagnosis. 

PMID- 25942045
TI  - Nickel-catalyzed direct amination of arenes with alkylamines.
AB  - The efficient nickel-catalyzed direct amination of arenes with simple alkylamines
      has been achieved with the assistance of a bidentate directing group through
      sp(2) C-H bond functionalization. Preliminary mechanistic investigations indicate
      that the reaction probably proceeds through a Ni(I)/Ni(III) catalytic pathway. 

PMID- 25942043
TI  - TrkB reduction exacerbates Alzheimer's disease-like signaling aberrations and
      memory deficits without affecting beta-amyloidosis in 5XFAD mice.
AB  - Accumulating evidence shows that brain-derived neurotrophic factor (BDNF) and its
      receptor tropomyosin-related kinase B (TrkB) significantly decrease early in
      Alzheimer's disease (AD). However, it remains unclear whether BDNF/TrkB
      reductions may be mechanistically involved in the pathogenesis of AD. To address
      this question, we generated 5XFAD transgenic mice with heterozygous TrkB knockout
      (TrkB(+/-).5XFAD), and tested the effects of TrkB reduction on AD-like features
      in this mouse model during an incipient stage that shows only modest amyloid-beta
      (Abeta) pathology and retains normal mnemonic function. TrkB(+/-) reduction
      exacerbated memory declines in 5XFAD mice at 4-5 months of age as assessed by the
      hippocampus-dependent spontaneous alternation Y-maze task, while the memory
      performance was not affected in TrkB(+/-) mice. Meanwhile, TrkB(+/-).5XFAD mice
      were normal in nest building, a widely used measure for social behavior,
      suggesting the memory-specific aggravation of AD-associated behavioral
      impairments. We found no difference between TrkB(+/-).5XFAD and 5XFAD control
      mice in cerebral plaque loads, Abeta concentrations including total Abeta42 and
      soluble oligomers and beta-amyloidogenic processing of amyloid precursor protein.
      Interestingly, reductions in hippocampal expression of AMPA/NMDA glutamate
      receptor subunits as well as impaired signaling pathways downstream to TrkB such
      as CREB (cAMP response element-binding protein) and Akt/GSK-3beta (glycogen
      synthase kinase-3beta) were observed in TrkB(+/-).5XFAD mice but not in 5XFAD
      mice. Among these signaling aberrations, only Akt/GSK-3beta dysfunction occurred
      in TrkB(+/-) mice, while others were synergistic consequences between TrkB
      reduction and subthreshold levels of Abeta in TrkB(+/-).5XFAD mice. Collectively,
      our results indicate that reduced TrkB does not affect beta-amyloidosis but
      exacerbates the manifestation of hippocampal mnemonic and signaling dysfunctions
      in early AD. 

PMID- 25942044
TI  - The role of 5-HT1A receptors in mediating acute negative effects of
      antidepressants: implications in pediatric depression.
AB  - Acute antidepressant exposure elevates the frequency of impulsive behavior and
      suicidal thoughts in children and adolescents with major depressive disorder
      (MDD). Long-term antidepressant treatment, however, is beneficial for pediatric
      MDD, so it is necessary to explore novel treatments that prevent the potentially
      dangerous consequences of acute antidepressant initiation. In the present study,
      a treatment strategy designed to reverse the acute negative behavioral effects of
      antidepressants was tested in rodents. Co-administration of the 5-HT1A receptor
      (5-HT1AR) antagonist WAY-100635 reversed the negative effects of acute
      fluoxetine, a serotonin reuptake inhibitor, but not reboxetine, a norepinephrine
      reuptake inhibitor, supporting the involvement of 5-HT1AR in mediating the
      negative consequences of acute selective serotonin reuptake inhibitor (SSRI)
      treatment. No 5-HT1AR antagonists are currently approved for use in pediatric
      populations, so alternative strategies should be explored. One such strategy was
      suggested based on the hypothesis that the rate of 5-HT1AR activation and the
      subsequent inhibition of serotonergic neuron activity caused by acute SSRI
      administration is proportional to the loading rate of an antidepressant. Existing
      pharmacological data were examined, and significant correlations were observed
      between the half-life of antidepressants and the rate of suicide-related events
      (SREs). Specifically, antidepressants with longer half-lives have lower rates of
      SREs. On the basis of these data, novel dosing strategies were developed for five
      antidepressants to mimic the pharmacological profile of the antidepressant with
      the longest half-life, fluoxetine. These dosing strategies could be used to
      decrease the rate of SREs associated with acute antidepressant treatment in
      pediatric MDD until an improved pharmacological treatment is developed. 

PMID- 25942046
TI  - Corneal Viscoelastic Properties in Patients with Angioid Streaks.
AB  - PURPOSE: The aim of this study is to investigate the possible corneal
      biomechanical changes in patients with angioid streaks and to understand if the
      calcified and thickened Bruch's membrane associated with angioid streaks
      influences elasticity of the eye and intraocular pressure. MATERIALS AND METHODS:
      Twelve eyes of 12 patients with angioid streaks (six males and six females) and
      12 eyes of 12 age- and sex-matched healthy volunteers were enrolled in the study.
      Corneal hysteresis (CH), corneal resistance factor (CRF), corneal compensated
      intraocular pressure (IOPcc) and Goldmann-correlated intraocular pressure (IOPg)
      were measured with an Ocular Response Analyzer (ORA). Central corneal thickness
      (CCT) was measured with an ultrasound pachymeter. RESULTS: Mean CRF and IOPg
      values in eyes with angioid streaks (12.10 +/- 1.27 and 17.76 +/- 2.73,
      respectively) were significantly higher than those in matched control eyes (10.70
      +/- 1.28 and 14.67 +/- 2.72, respectively; p = 0.01 for CRF, p = 0.007 for IOPg).
      There was no statistically significant difference between eyes with angioid
      streaks and matched control eyes in measured CH, IOPcc and CCT values (p = 0.29,
      p = 0.09 and p = 0.86, respectively). CONCLUSIONS: This study revealed that
      angioid streaks can affect corneal biomechanical properties by increasing CRF, as
      compared to the healthy eyes. Increased CRF means increased resistance for effect
      of IOP on eye so it can be speculated that these patients tend to be more
      protected for glaucoma.

PMID- 25942047
TI  - Cell orientation gradients on an inverse opal substrate.
AB  - The generation of cell gradients is critical for understanding many biological
      systems and realizing the unique functionality of many implanted biomaterials.
      However, most previous work can only control the gradient of cell density and
      this has no effect on the gradient of cell orientation, which has an important
      role in regulating the functions of many connecting tissues. Here, we report on a
      simple stretched inverse opal substrate for establishing desired cell orientation
      gradients. It was demonstrated that tendon fibroblasts on the stretched inverse
      opal gradient showed a corresponding alignment along with the elongation gradient
      of the substrate. This "random-to-aligned" cell gradient reproduces the insertion
      part of many connecting tissues, and thus, will have important applications in
      tissue engineering. 

PMID- 25942049
TI  - Partial surface tension of components of a solution.
AB  - First, extending the boundaries of the thermodynamic framework of Gibbs, a
      definition of the partial surface tension of a component of a solution is
      provided. Second, a formal thermodynamic relationship is established between the
      partial surface tensions of different components of a solution and the surface
      tension of the same solution. Third, the partial surface tension of a component
      is derived as a function of bulk and surface concentrations of the given
      component, using general equations for the thermodynamics of solutions. The above
      equations are derived without an initial knowledge of the Gibbs adsorption
      equation and without imposing any restrictions on the thickness or structure of
      the surface region of the solution. Only surface tension and the composition of
      the surface region are used as independent thermodynamic parameters, similar to
      Gibbs, who used only the surface tension of the solution and the relative surface
      excesses of the components. The final result formally coincides with the
      historical Butler equation (1932), but without its theoretical restrictions.
      (Butler used too many unnecessary model restrictions during his work: he started
      from the Gibbs adsorption equation, and he assumed the existence of a surface
      monolayer.) Thus, the renovated Butler equation has gained general validity in
      this article. It was applied to derive both the Langmuir equation and the Gibbs
      adsorption equation, but the latter two equations do not follow from each other.
      Thus, it is shown that logically (not historically) the renovated Butler equation
      is a root equation for surface tension and the adsorption of solutions. It can be
      used to perform calculations for specific systems if the corresponding specific
      experimental data/models are loaded into it. In this case, both surface tension
      and surface composition can be calculated from the renovated Butler equation,
      which cannot be done using the Gibbs adsorption equation alone. 

PMID- 25942048
TI  - Comment on "Sphagnum mosses from 21 ombrotrophic bogs in the Athabasca bituminous
      sands region show no significant atmospheric contamination of 'heavy metals'".

PMID- 25942050
TI  -   Surgical management of chronic wounds T.
AB  - The management of chronic wounds poses a challenge to internists and surgeons
      alike. Chronic wounds are trapped in a nonadvancing phase of healing and are
      unable to progress through the sequential stages of tissue repair. The primary
      roles of surgery in managing these wounds are debridement and wound closure.
      Surgical debridement releases the chronic wound from its arrested state by
      removing nonviable tissue, bacteria, and other inhibitory factors, effectively
      converting it into an acute wound that can undergo healing more effectively.
      Debridement can be accomplished with a number of techniques, and recent
      innovations in the wound care industry have added invaluable tools to the wound
      healing armamentarium. While surgical debridement and closure provide definitive
      treatment, identifying and treating the underlying cause of a chronic wound is
      critical to promoting timely healing and preventing wound recurrence. 

PMID- 25942051
TI  -  Charcot foot deformity: surgical treatment options.
AB  - Charcot arthropathy can have a significant impact on the patient regarding limb
      salvage and overall health. With longer survival rates of patients with diabetes
      the incidence of Charcot arthropathy has been noted to be increasing in
      occurrence within the last several years. The treatment of the Charcot foot, both
      nonoperatively and operatively, has been a topic of debate as the number of
      complex wounds and lower extremity deformities has been increasing. In the past,
      amputation was arguably the most common surgical treatment. However, with the
      advent of a better understanding of the disease process and the development of
      new fixation and surgical techniques, more potential surgical treatment options
      besides amputation now exist. For any healthcare provider involved in the care of
      the diabetic foot, it is important to know when to seek referral or consultation
      for possible surgical correction, and what options are available in the limb
      salvage treatment arena. 

PMID- 25942052
TI  -  Surgical management of the diabetic foot.
AB  - Wounds of the foot are the most common reason for diabetes-related hospital
      admissions. In many of these cases, surgical intervention is the best option.
      This article will review the risk factors for foot wounds in people with
      diabetes, discuss preventative and surgical strategies, and present surgical
      management techniques to treat ulceration and chronic infection in these wounds.
      . 

PMID- 25942053
TI  - Endothelial inflammatory transcriptional responses to an altered plasma exposome
      following inhalation of diesel emissions.
AB  - BACKGROUND: Air pollution, especially emissions derived from traffic sources, is
      associated with adverse cardiovascular outcomes. However, it remains unclear how
      inhaled factors drive extrapulmonary pathology. OBJECTIVES: Previously, we found
      that canonical inflammatory response transcripts were elevated in cultured
      endothelial cells treated with plasma obtained after exposure compared with pre
      exposure samples or filtered air (sham) exposures. While the findings confirmed
      the presence of bioactive factor(s) in the plasma after diesel inhalation, we
      wanted to better examine the complete genomic response to investigate (1) major
      responsive transcripts and (2) collected response pathways and ontogeny that may
      help to refine this method and inform the pathogenesis. METHODS: We assayed
      endothelial RNA with gene expression microarrays, examining the responses of
      cultured endothelial cells to plasma obtained from six healthy human subjects
      exposed to 100 MUg/m(3) diesel exhaust or filtered air for 2 h on separate
      occasions. In addition to pre-exposure baseline samples, we investigated samples
      obtained immediately-post and 24 h-post exposure. RESULTS: Microarray analysis of
      the coronary artery endothelial cells challenged with plasma identified 855
      probes that changed over time following diesel exhaust exposure. Over
      representation analysis identified inflammatory cytokine pathways were
      upregulated both at the 2 and 24 h conditions. Novel pathways related to FOXO
      transcription factors and secreted extracellular factors were also identified in
      the microarray analysis. CONCLUSIONS: These outcomes are consistent with our
      recent findings that plasma contains bioactive and inflammatory factors following
      pollutant inhalation and provide a novel pathway to explain the well-reported
      extrapulmonary toxicity of ambient air pollutants.

PMID- 25942055
TI  - Gas-phase structure and reactivity of the keto tautomer of the deoxyguanosine
      radical cation.
AB  - Guanine radical cations are formed upon oxidation of DNA. Deoxyguanosine (dG) is
      used as a model, and the gas-phase infrared (IR) spectroscopic signature and gas
      phase unimolecular and bimolecular chemistry of its radical cation, dG(+), A,
      which is formed via direct electrospray ionisation (ESI/MS) of a methanolic
      solution of Cu(NO3)2 and dG, are examined. Quantum chemistry calculations have
      been carried out on 28 isomers and comparisons between their calculated IR
      spectra and the experimentally-measured spectra suggest that A exists as the
      ground-state keto tautomer. Collision-induced dissociation (CID) of A proceeds
      via cleavage of the glycosidic bond, while its ion-molecule reactions with amine
      bases occur via a number of pathways including hydrogen-atom abstraction, proton
      transfer and adduct formation. A hidden channel, involving isomerisation of the
      radical cation via adduct formation, is revealed through the use of two stages of
      CID, with the final stage of CID showing the loss of CH2O as a major
      fragmentation pathway from the reformed radical cation, dG(+). Quantum chemistry
      calculations on the unimolecular and bimolecular reactivity are also consistent
      with A being present as a ground-state keto tautomer.

PMID- 25942054
TI  - The beryllium bronchoalveolar lavage lymphocyte proliferation test: indicator of
      beryllium sensitization, inflammation or both?
AB  - CONTEXT: We had available records on over 300 workers evaluated with the
      beryllium bronchoalveolar lavage lymphocyte proliferation test (BeBALLPT) at
      three expert chronic beryllium disease (CBD) diagnostic centers. OBJECTIVE: The
      objective was to describe the contribution of the BeBALLPT to classification of
      workers with respect to beryllium sensitization (BeS) and beryllium-induced lung
      inflammation. METHODS: Company records were used to identify beryllium workers
      who had undergone diagnostic bronchoscopy with BeBALLPT. Clinical, work and
      smoking information was abstracted from electronic and paper databases. We
      analyzed factors influencing BeBALLPT outcome, and its relation to blood
      determined BeS and granulomatous inflammation. RESULTS: Positive BeBALLPTs
      contributed evidence of BeS in subjects without prior positive beryllium blood
      lymphocyte proliferation tests (BeBLPTs) and of pulmonary inflammation in persons
      without granulomata evident on lung biopsy. Positive BeBALLPTs were associated
      with positive BeBLPTs and more strongly with granulomata. The rate of both
      positive BeBALLPT and granulomata increased with time worked through 4 years and
      were lower in smoking subjects. The false negative rate of the BeBALLPT was 20%.
      CONCLUSION: A positive BeBALLPT is closely linked to the presence of granulomata
      on lung biopsy and can be considered as an indicator of lung inflammation in
      addition to BeS. The ability to use BeBALLPT as a substitute for the more risky
      lung biopsy is limited by the BeBALLPT false negative rate and lack of
      information on the false positive rate. It is not recommended that a positive
      BeBALLPT be considered sufficient evidence for both lung inflammation and BeS.

PMID- 25942056
TI  - Combustion Processes as a Source of High Levels of Indoor Hydroxyl Radicals
      through the Photolysis of Nitrous Acid.
AB  - Hydroxyl radicals (OH) are known to control the oxidative capacity of the
      atmosphere but their influence on reactivity within indoor environments is
      believed to be of little importance. Atmospheric direct sources of OH include the
      photolysis of ozone and nitrous acid (HONO) and the ozonolysis of alkenes. It has
      been argued that the ultraviolet light fraction of the solar spectrum is largely
      attenuated within indoor environments, thus, limiting the extent of photolytic OH
      sources. Conversely, the ozonolysis of alkenes has been suggested as the main
      pathway of OH formation within indoor settings. According to this hypothesis the
      indoor OH radical concentrations span in the range of only 10(4) to 10(5) cm(-3).
      However, recent direct OH radical measurements within a school classroom yielded
      OH radical peak values at moderate light intensity measured at evenings of 1.8 *
      10(6) cm(-3) that were attributed to the photolysis of HONO. In this work, we
      report results from chamber experiments irradiated with varying light intensities
      in order to mimic realistic indoor lighting conditions. The exhaust of a burning
      candle was introduced in the chamber as a typical indoor source causing a sharp
      peak of HONO, but also of nitrogen oxides (NOx). The photolysis of HONO yields
      peak OH concentration values, that for the range of indoors lightning conditions
      were estimated in the range 5.7 *. 10(6) to 1.6 * 10(7) cm(-3). Excellent
      agreement exists between OH levels determined by a chemical clock and those
      calculated by a simple PSS model. These findings suggest that significant OH
      reactivity takes place at our dwellings and the consequences of this reactivity
      that is, formation of secondary oxidants-ought to be studied hereafter. 

PMID- 25942058
TI  - Characterisation of the deleted in azoospermia like (Dazl)-green fluorescent
      protein mouse model generated by a two-step embryonic stem cell-based strategy to
      identify pluripotent and germ cells.
AB  - The deleted in azoospermia like (Dazl) gene is preferentially expressed in germ
      cells; however, recent studies indicate that it may have pluripotency-related
      functions. We generated Dazl-green fluorescent protein (GFP) transgenic mice and
      assayed the ability of Dazl-driven GFP to mark preimplantation embryo
      development, fetal, neonatal and adult tissues, and in vitro differentiation from
      embryonic stem cells (ESCs) to embryoid bodies (EBs) and to primordial germ cell
      (PGC)-like cells. The Dazl-GFP mice were generated by a two-step ESC-based
      strategy, which enabled primary and secondary screening of stably transfected
      clones before embryo injection. During preimplantation embryo stages, GFP was
      detected from the zygote to blastocyst stage. At Embryonic Day (E) 12.5, GFP was
      expressed in gonadal ridges and in neonatal gonads of both sexes. In adult mice,
      GFP expression was found during spermatogenesis from spermatogonia to elongating
      spermatids and in the cytoplasm of oocytes. However, GFP mRNA was also detected
      in other tissues harbouring multipotent cells, such as the intestine and bone
      marrow. Fluorescence was maintained along in vitro Dazl-GFP ESC differentiation
      to EBs, and in PGC-like cells. In addition to its largely known function in germ
      cell development, Dazl could have an additional role in pluripotency, supporting
      these transgenic mice as a valuable tool for the prospective identification of
      stem cells from several tissues.

PMID- 25942057
TI  - Deciphering the unconventional peptide binding to the PDZ domain of MAST2.
AB  - Phosphatase and tensin homologue (PTEN) and microtubule-associated serine
      threonine kinase 2 (MAST2) are key negative regulators of survival pathways in
      neuronal cells. The two proteins interact via the PDZ (PSD-95, Dlg1, Zo-1) domain
      of MAST2 (MAST2-PDZ). During infection by rabies virus, the viral glycoprotein
      competes with PTEN for interaction with MAST2-PDZ and promotes neuronal survival.
      The C-terminal PDZ-binding motifs (PBMs) of the two proteins bind similarly to
      MAST2-PDZ through an unconventional network of connectivity involving two anchor
      points. Combining stopped-flow fluorescence, analytical ultracentrifugation
      (AUC), microcalorimetry and NMR, we document the kinetics of interaction between
      endogenous and viral ligands to MAST2-PDZ as well as the dynamic and structural
      effects of these interactions. Viral and PTEN peptide interactions to MAST2-PDZ
      occur via a unique kinetic step which involves both canonical C-terminal PBM
      binding and N-terminal anchoring. Indirect effects induced by the PBM binding
      include modifications to the structure and dynamics of the PDZ dimerization
      surface which prevent MAST2-PDZ auto-association. Such an energetic communication
      between binding sites and distal surfaces in PDZ domains provides interesting
      clues for protein regulation overall. 

PMID- 25942059
TI  - Synthesis of cytotoxic 2,2-difluoroderivatives of dihydrobetulinic acid and
      allobetulin and study of their impact on cancer cells.
AB  - In this article, we describe the preparation and cytotoxic properties of a small
      focused library of lupane and 18alpha-oleanane triterpenoids that contain a
      combination of two structural motifs known to enhance the biological activities.
      First, we introduced two fluorine atoms to position 2 of the skeleton. Second, we
      synthesized a set of hemiester prodrugs, which were intended to increase the
      solubility and activity. Starting from betulin, we obtained two hydroxyketones
      (derivatives of dihydrobetulinic acid and allobetulin) and their fluorination
      using DAST provided 2,2-difluoro-3-oxo-compounds as the main products. Then the 3
      oxo group in each derivative was reduced by NaBH4 to obtain 3beta-hydroxy
      compounds suitable for modifying by various hemiesters. We prepared 21 compounds,
      11 of them new, their cytotoxicity was tested on T lymphoblastic leukemia CCRF
      CEM cells first and the most active derivatives were selected for screening on
      another six tumor and two non-tumor cell lines. All of them showed selectivity
      against cancer lines with therapeutic index between 2 and 8. All hemiesters had
      activity in the same range as the free hydroxyl derivatives and they would be
      suitable prodrugs for future in vivo experiments. Interestingly, all hemiesters
      of 2,2-difluorodihydrobetulonic acid had higher activity against p53 knock-out
      p53-/- cancer cell line than against the non-mutated analog. In active
      derivatives, the cell cycle was analyzed by flow cytometry and several compounds
      slowed down cell cycle progression through G0/G1 or S-phase.

PMID- 25942060
TI  - Design, synthesis and structure-activity relationship of phthalimides endowed
      with dual antiproliferative and immunomodulatory activities.
AB  - The present work reports the synthesis and evaluation of the antitumour and
      immunomodulatory properties of new phthalimides derivatives designed to explore
      molecular hybridization and bioisosterism approaches between thalidomide,
      thiosemicarbazone, thiazolidinone and thiazole series. Twenty-seven new molecules
      were assessed for their immunosuppressive effect toward TNFalpha, IFNgamma, IL-2
      and IL-6 production and antiproliferative activity. The best activity profile was
      observed for the (6a-f) series, which presents phthalyl and thiazolidinone
      groups. 

PMID- 25942061
TI  - Methodological Aspects of Plant Sterol and Stanol Measurement.
AB  - Cholesterol, its biosynthetic precursors, its metabolite 5alpha-cholestanol and
      plant sterols are widely used today in clinical lipid research as surrogate
      markers of cholesterol synthesis and absorption. Advances in analytical methods
      for the determination of serum noncholesterol sterols and stanols within the last
      century are highlighted. This review focuses on sample preparation, separation,
      and detection techniques. Various aspects related to sterol and stanol analysis
      from biological samples are discussed. 

PMID- 25942062
TI  - Comparing substrate specificity of two UDP-sugar pyrophosphorylases and efficient
      one-pot enzymatic synthesis of UDP-GlcA and UDP-GalA.
AB  - Uridine 5'-diphosphate-glucuronic acid (UDP-GlcA) and UDP-galacturonic acid (UDP
      GalA), the unique carboxylic acid-formed sugar nucleotides, are key precursors
      involved in the biosynthesis of numerous cell components. Limited availability of
      those components has been hindering the development of efficient ways towards
      facile synthesis of bioactive glycans such as glycosaminoglycans. In current
      study, we biochemically characterized two UDP-sugar pyrophosphorylases from
      Arabidopsis thaliana (AtUSP) and Bifidobacterium infantis ATCC15697 (BiUSP), and
      compared their activities towards a panel of sugar-1-phosphates and derivatives.
      Both enzymes showed significant pyrophosphorylation activities towards GlcA-1
      phosphate, and AtUSP also exhibited comparable activity towards GalA-1-phosphate.
      By combining with monosaccharide-1-phosphate kinases, we have developed an
      efficient and facile one-pot three-enzyme approach to quickly obtain hundreds
      milligrams of UDP-GlcA and UDP-GalA. 

PMID- 25942063
TI  - Characterization of a novel polysaccharide with anti-colon cancer activity from
      Lactobacillus helveticus MB2-1.
AB  - The present study aimed at investigating the potential anti-colon cancer activity
      of three purified exopolysaccharides fractions (LHEPS-1, LHEPS-2 and LHEPS-3)
      from the Lactobacillus helveticus MB2-1. The experimental evidence showed that
      LHEPS-1 significantly inhibited cell proliferation of human colon cancer Caco-2
      cells in both time- and concentration-dependent manners. In contrast, no
      significant improvements of the inhibitory effects of LHEPS-2 and LHEPS-3 on Caco
      2 cells were observed with increasing sample concentrations or prolonged
      incubation time. Furthermore, the structure of LHEPS-1 was elucidated using
      methylated analysis, gas chromatography-mass spectroscopy (GC-MS) and nuclear
      magnetic resonance spectroscopy (NMR), including one- and two-dimensional nuclear
      magnetic resonance (1D and 2D NMR). Results indicated that the LHEPS-1 consisted
      of a decasaccharide repeating unit with the following structure (n ~ 122): Our
      results suggested that the LHEPS-1 produced by L. helveticus MB2-1 might be
      suitable for using as natural anti-colon cancer drugs and functional foods
      ingredients.

PMID- 25942064
TI  - Inter-individual Variability in Response to Plant Sterol and Stanol Consumption.
AB  - Despite the abundance of clinical trial data demonstrating the cholesterol
      lowering action of plant sterol supplementation, substantial variability in
      efficacy exists in responsiveness across individuals. The goal of this review is
      to examine factors responsible for this heterogeneity in responsiveness of blood
      cholesterol levels to dietary plant sterols. Although initially thought to be due
      to random noise in the data, demonstrated consistency in degree of responsiveness
      in the context of controlled feeding designs from person to person suggests that
      other systematic drivers are responsible. Genetic explanations explaining this
      phenomenon appear to be gaining momentum. Particularly, single nucleotide
      polymorphisms within the genes coding for CYP7A1 and ApoE, as well as possibly
      other genes including ABCG5 and ABCG8, exist as predictors of whether LDL-C
      levels will decrease or even increase subsequent to plant sterol administration.
      In summary, nutrigenetic differences across genes associated with cholesterol
      trafficking pathways may be important in predicting how well any given individual
      will respond to dietary interventions. It is anticipated that eventually genetic
      tests will be developed that can guide health care professionals to optimize
      dietary strategies for health optimization. 

PMID- 25942065
TI  - Ultra-low dose of intravitreal bevacizumab in the treatment of retinopathy of
      prematurity.
AB  - Intravitreal bevacizumab is an increasingly common treatment choice for posterior
      retinopathy of prematurity. Despite concern about its systemic effects, there
      have been few studies on the lowest effective dose. The authors describe a case
      that was successfully treated with 0.16 mg of bevacizumab, the first time this
      dose has been reported.

PMID- 25942066
TI  - Prenatal diagnosis of colobomatous microphthalmos.
AB  - Optic nerve coloboma and microphthalmos with colobomatous cyst are rare
      congenital anomalies that are difficult to detect on prenatal ultrasonography and
      magnetic resonance imaging. Only four cases of optic nerve coloboma and two cases
      of microphthalmos with colobomatous cyst have been detected on prenatal imaging.
      The authors report a case of a fetus initially suspected to have retinoblastoma
      of the right eye on prenatal ultrasonography who was later diagnosed as having
      microphthalmos on fetal magnetic resonance imaging. Following delivery, she was
      noted to have microphthalmos with colobomatous cyst of the right eye and optic
      nerve coloboma of the left eye. The authors also review the prenatal ocular
      imaging findings of the differential diagnosis.

PMID- 25942068
TI  - Reducing High-Risk Drinking Among Student-Athletes: The Effects of a Targeted
      Athlete-Specific Brief Intervention.
AB  - OBJECTIVE: This study examined the effects of a single-session motivational
      interviewing-based in-person brief alcohol intervention that contained student
      athlete-specific personalized drinking feedback. PARTICIPANTS: Participants were
      170 National Collegiate Athletic Association Division I student-athletes meeting
      screening criteria for heavy episodic drinking. METHODS: Baseline assessments of
      alcohol use frequency and quantity, norm perceptions of peers' alcohol use,
      experiences of negative consequences, and use of protective behaviors were
      administered to student-athletes prior to a 1-session brief intervention
      containing personalized feedback highlighting the relationship between alcohol
      use and athletic performance. Follow-up assessment was conducted 3 months post
      intervention. RESULTS: Student-athletes participating in the athlete-specific
      brief intervention showed significant reductions in their alcohol use and alcohol
      related negative consequences, increases in use of protective behavioral
      strategies, and corrections in norm misperceptions at 3 months post intervention
      relative to a no-treatment comparison group. CONCLUSIONS: Student-athlete
      specific brief alcohol interventions show promise in addressing high-risk
      drinking, reducing associated harms, and supporting health.

PMID- 25942069
TI  - Molecular Structure-Intersystem Crossing Relationship of Heavy-Atom-Free BODIPY
      Triplet Photosensitizers.
AB  - A thiophene-fused BODIPY chromophore displays a large triplet-state quantum yield
      (PhiT = 63.7%). In contrast, when the two thienyl moieties are not fused into the
      BODIPY core, intersystem crossing (ISC) becomes inefficient and PhiT remains low
      (PhiT = 6.1%). First-principles calculations including spin-orbit coupling (SOC)
      were performed to quantify the ISC. We found larger SOC and smaller singlet
      triplet energy gaps for the thiophene-fused BODIPY derivative. Our results are
      useful for studies of the photochemistry of organic chromophores. 

PMID- 25942070
TI  - Reducing Communication Apprehension for New Patients Through Information Found
      Within Physicians' Biographies.
AB  - This study investigated whether state communication apprehension (CA) with
      physicians, for high CA patients, can be reduced before consultations by
      manipulating information found within physicians' online biographies.
      Participants were presented with three experimentally manipulated physician
      biographies and asked to choose which physician they would want to visit to get a
      hypothetical ailment checked out. Guided by uncertainty reduction theory, results
      support a path model where increases in perceived similarities between a patient
      and doctor led to greater uncertainty reduction, greater liking, and subsequent
      reductions in CA with the physician for high CA participants. In addition, the
      majority of participants decided to visit the physician with whom they perceived
      the greatest similarity. The importance of reducing CA in the medical context is
      discussed, as well as theoretical implications for communication researchers. The
      results also provide practical guidance for health care systems to help improve
      their current physician biographical offerings available to prospective patients.

PMID- 25942071
TI  - Analysis of serpentine polymorphs in investigations of natural occurrences of
      asbestos.
AB  - This work investigates potential analytical variability in environmental
      investigations of natural occurrences of asbestos (NOA) due to intergrown
      serpentine minerals. Franciscan complex and serpentinite rock samples were
      obtained from likely NOA sites in coastal Northern California with geographic
      information system (GIS) maps, then analyzed using polarized light microscopy
      (PLM), transmission electron microscopy with energy-dispersive X-ray analysis and
      selected area electron diffraction (TEM/SAED/EDS), and environmental scanning
      electron microscopy with EDS (ESEM/EDS). Non-asbestos serpentine fibers were
      superficially similar to chrysotile but were differentiated quickly using TEM
      morphology criteria and reference SAED overlays. 94 NOA fibers were classified as
      asbestiform chrysotile (62%), polygonal serpentine (34%), lizardite scrolls (2%),
      and lizardite laths (2%). Chrysotile fibril widths (mean = 42 nm) were
      significantly different from those of polygonal serpentine and lizardite laths
      (167 and 505 nm, respectively), but not lizardite scrolls (37 nm). Due to
      differing preparations and microscope resolutions, TEM analyses investigated a
      distinct, smaller population of particles (0.01-10 MUm) than did PLM analyses (10
      100 MUm). A higher proportion of asbestiform phases in the finer fraction could
      potentially bias TEM bulk percent asbestos determinations. ESEM/EDS of
      intermediate particle size ranges revealed 20-200 MUm, elongated particles with
      intermixed asbestiform and non-asbestiform structures on their surfaces. These
      particles were too thick and complex to be resolved by PLM, and too massive to be
      detected by TEM. These large particles are likely to exist in samples prepared by
      mechanical crushing or grinding, but are not likely to be generated by
      "releasable asbestos" methods. 

PMID- 25942074
TI  - Surprisingly High Conductivity and Efficient Exciton Blocking in Fullerene/Wide
      Energy-Gap Small Molecule Mixtures.
AB  - We find that mixtures of C60 with the wide energy gap, small molecular weight
      semiconductor bathophenanthroline (BPhen) exhibit a combination of surprisingly
      high electron conductivity and efficient exciton blocking when employed as buffer
      layers in organic photovoltaic cells. Photoluminescence quenching measurements
      show that a 1:1 BPhen/C60 mixed layer has an exciton blocking efficiency of 84 +/
      5% compared to that of 100% for a neat BPhen layer. This high blocking
      efficiency is accompanied by a 100-fold increase in electron conductivity
      compared with neat BPhen. Transient photocurrent measurements show that charge
      transport through a neat BPhen buffer is dispersive, in contrast to nondispersive
      transport in the compound buffer. Interestingly, although the conductivity is
      high, there is no clearly defined insulating-to-conducting phase transition with
      increased insulating BPhen fraction. Thus, we infer that C60 undergoes nanoscale
      (<10 nm domain size) phase segregation even at very high (>80%) BPhen fractions. 

PMID- 25942072
TI  - Fasting Enhances Pyroglutamyl Peptidase II Activity in Tanycytes of the
      Mediobasal Hypothalamus of Male Adult Rats.
AB  - Fasting down-regulates the hypothalamus-pituitary-thyroid (HPT) axis activity
      through a reduction of TRH synthesis in neurons of the parvocellular
      paraventricular nucleus of the hypothalamus (PVN). These TRH neurons project to
      the median eminence (ME), where TRH terminals are close to the cytoplasmic
      extensions of beta2 tanycytes. Tanycytes express pyroglutamyl peptidase II
      (PPII), the TRH-degrading ectoenzyme that controls the amount of TRH that reaches
      the anterior pituitary. We tested the hypothesis that regulation of ME PPII
      activity is another mechanism by which fasting affects the activity of the HPT
      axis. Semiquantitative in situ hybridization histochemistry data indicated that
      PPII and deiodinase 2 mRNA levels increased in tanycytes after 48 hours of
      fasting. This increase was transitory, followed by an increase of PPII activity
      in the ME, and a partial reversion of the reduction in PVN pro-TRH mRNA levels
      and the number of TRH neurons detected by immunohistochemistry. In fed animals,
      adrenalectomy and corticosterone treatment did not change ME PPII activity 72
      hours later. Methimazole-induced hypothyroidism produced a profound drop in
      tanycytes PPII mRNA levels, which was reverted by 3 days of treatment with T4.
      The activity of thyroliberinase, the serum isoform of PPII, was increased at most
      fasting time points studied. We conclude that delayed increases in both the ME
      PPII as well as the thyroliberinase activities in fasted male rats may facilitate
      the maintenance of the deep down-regulation of the HPT axis function, despite a
      partial reactivation of TRH expression in the PVN. 

PMID- 25942073
TI  - Adrenal and Ovarian Phenotype of a Tissue-Specific Urocortin 2-Overexpressing
      Mouse Model.
AB  - Urocortin 2 (UCN2) is a neuropeptide of the CRH family, involved in homeostatic
      mechanisms, the stress response, and control of anxiety. To elucidate the effects
      of UCN2 on steroidogenesis, we developed a mouse model that allows a Cre
      recombinase-determined conditional overexpression of UCN2 (UCN2-COE). In these
      mice SF1-Cre-driven overexpression of UCN2 was restricted to the adrenal glands,
      gonads, and parts of the hypothalamus. UCN2-COE animals of both sexes revealed
      significantly higher plasma UCN2 levels and significantly higher UCN2 expression
      levels in the adrenals and ovaries. In contrast, the baseline expression of UCN2
      was already high in the testes of control mice with no further increase
      achievable in UCN2-COE animals. Adrenal steroidogenesis of UCN2-COE animals was
      investigated under baseline conditions, upon an ACTH stimulation test, and
      following a restraint stress test. A tendency toward lower expression of
      steroidogenic enzymes was detectable in UCN2-COE animals of both sexes with
      slight differences between males and females. A similar reduction in the
      expression levels of the final steps of ovarian steroidogenesis, accompanied by
      reduced plasma estradiol levels, was observed in female UCN2-COE animals. Thus,
      adrenal UCN2 overexpression resulted in down-regulation of adrenal
      steroidogenesis, suggesting a reduction in the stress response in the mouse
      (stress coping behavior). Similarly, UCN2 overexpression in the ovaries caused a
      decrease in steroidogenesis and reduction of follicles that had undergone
      ovulation. Nevertheless, this finding was not associated with reduced fertility. 

PMID- 25942075
TI  - Age at Birth of First Child and Fecundity of Women Survivors of Childhood Acute
      Lymphoblastic Leukemia (1987-2007): A Study of the Childhood Cancer Registry of
      the Rhone-Alpes Region in France (ARCERRA).
AB  - We studied the fecundity of 174 successive ALL (1987-2007) in females of the
      Childhood Cancer Registry of the Rhone-Alpes Region (ARCERRA) with a median age
      at follow-up of 25.6 years (18.0-37.4). We distinguished five treatment groups:
      Group Ia, chemotherapy only (n = 130); Ib, chemotherapy with cranial radiotherapy
      (n = 10); II, TBI conditioning allograft (n = 27); III, chemotherapy conditioning
      allograft (n = 4); IV, TBI conditioning autograft (n = 3). Twenty-three women had
      their first child at the mean age of 25.8 +/-3.0 years, i.e., 2.0 +/-2.9 years
      earlier than the general population of the Rhone-Alpes region (P = 0.003). The
      standardized fertility ratio (SFR), expressed as the number of actual births
      observed (O) to the number that would be expected in women of the same age in the
      general population (E) (SFR = O/E) was decreased for Group Ia (0.62; 95%CI, 0.52
      0.74) and collapsed in Group II (0.17; 0.11-0.25). In univariate analysis, TBI (P
      = 0.013) and alkylating agents (P = 0.01) were negatively correlated with
      fecundity, but not with the age at diagnosis or the anthracyclines doses. In
      multivariate analysis including TBI and alkylating agents, we still found a
      negative correlation between TBI (P = 0.035), as well as alkylating agents (P =
      0.028), and fecundity. More precisely, fecundity was negatively correlated with
      cumulative cyclophosphamide equivalent dose (P = 0.001), with a fecundity
      decreased for >=1g/m(2), but without any dose effect; results not found in the
      Group Ia. Age at first child seems younger but the young median age of the cohort
      not allows concluding; fecundity is collapsed after fractionated total body
      irradiation and decreased after chemotherapy without any demonstrable cause. A
      delay of fertility is not excluded.

PMID- 25942076
TI  - [The "Psychiatrie-Enquete" - the German Report on the State of Psychiatry in
      1975].
AB  - Forty years ago an expert-commission submitted a report on the deplorable state
      of German psychiatric care, called the "Psychiatrie-Enquete" to the Bundestag,
      the German parliament. The Report initiated a substantial change of Psychiatric
      services in the country. Inhuman treatment and living conditions were superseded.
      Mental hospitals were not completely abolished. But they lost their importance in
      favour of decentralized psychiatric services including departments at general
      hospitals, day hospitals and outpatient services. Custodial care was largely
      successfully developed into therapeutic and rehabilitative care. This article
      attempts a mildly critical evaluation of the Enquete 40 years after. 

PMID- 25942077
TI  - [Crisis Cards for the Prevention of Compulsory Hospitalization].
AB  - OBJECTIVE: To assess early signs of mental-health crises, treatment-specific
      demands and individual coping strategies from the subjective patients'
      perspective, and to categorize these specifications on the patients' crisis
      cards. METHODS: A sample of 108 psychiatric patients with severe mental disorders
      is currently taking part in an intervention programme targeting the reduction of
      compulsory re-admission to psychiatry. As part of the programme, patients fill in
      a crisis card. Data are analysed by a qualitative approach using content
      analysis. RESULTS: A variety of early signs of a crisis was specified by the
      psychiatric patients, most often negative emotions/thoughts (48 %). Likewise, the
      analysis revealed a wide range of treatment-specific preferences and individual
      strategies to cope with mental-health crises. CONCLUSIONS: Drawing up a crisis
      card in collaboration with a patient and discussing its contents might be used as
      a treatment resource and be beneficial to increase the patient's empowerment.
      Essential for the long-term prevention of mental-health crises and relapses is
      the regular reflection of the contents of a patient's crisis card.

PMID- 25942078
TI  - [Iranian and German Patients in an Urban Psychiatric Practice: Are they Different
      Concerning Frequency and Severity of Mental Illness?].
AB  - OBJECTIVE: Frequency and severity of mental illness in patient samples of two
      culturally different origins. METHODS: Employment of the structured interview
      (Mini-DIPS) and self-assessment questionnaires on depression (BDI-II) and general
      psychiatric symptom load (SCL-90-R) as well as posttraumatic symptoms (ETI) and
      sense of coherence (SOC-29) in 55 Iranian and 51 German patients of a psychiatric
      practice. RESULTS: Iranian patients show higher symptom load, but also higher
      resilience. CONCLUSION: The higher burden of symptoms in Iranians can be
      attributed to traumatic experiences before migration on the one hand and is
      associated with insufficient language proficiency on the other hand.

PMID- 25942079
TI  - [Psychiatric Emergencies in Psychiatric Hospitals in Germany].
AB  - Objective: Psychiatric hospitals are confronted with high rates of psychiatric
      emergencies. There are, however, only few investigations that focus on
      psychiatric emergency care in German psychiatric hospitals, their supply
      structures and diagnostic and treatment standards. The aim of the survey was a
      systematic acquisition of the diagnostic and therapeutic approach in treating
      psychiatric emergencies in German psychiatric hospitals. Methods: We conducted a
      survey in psychiatric hospitals throughout Germany. The questionnaire consisted
      of questions concerning the structures of supply and diagnostic and therapeutic
      standards treating psychiatric emergencies. Results: 42 % of all admissions to
      German psychiatric hospitals were emergency admissions. More than 60 % of the
      patients in psychiatric emergency ambulances had to receive inpatient treatment.
      As standard procedures for medical clearing in psychiatric emergencies physical
      examination, measurement of heart rate and blood pressure and conducting certain
      laboratory tests and breath alcohol were named. The most common
      psychopharmacological agents for emergency situations were diazepam, lorazepam,
      haloperidol and zuclopenthixol. Conclusion: Diagnosing and treating psychiatric
      emergencies need more standardisation. More specific data is required to generate
      diagnostic and therapeutic standards.

PMID- 25942080
TI  - [Assessment-Based Home Treatment for People with Severe Psychotic Disorders].
AB  - OBJECTIVE: Although there is growing evidence for clinical effectiveness of
      crisis resolution teams (also called Home Treatment Teams) for patients with
      severe psychotic disorders, a lot of studies suffer from poor model fidelity,
      which leads to an ignorance of specific effective factors. METHODS: Here we
      present the implementation of an assessment-based Home Treatment in Germany.
      Assessment-derived therapeutic tasks are shared between team members by a
      manualized process. RESULTS: We visited 32 patients almost 600 times in 15
      months. The median was 15.5 visits per patient. Adherence to Home Treatment
      intervention was significantly stronger (unplanned discharge 16 %) compared to
      prior hospitalization (unplanned discharge 50 %) (Chi-square test, p = 0.003).
      CONCLUSION: Applying this model, a detailed definition of specific tasks for team
      members leads to a high model fidelity and increases patients' compliance to
      therapy.

PMID- 25942081
TI  - Tetradentate metal complexes derived from cephalexin and 2,6-diacetylpyridine
      bis(hydrazone): Synthesis, characterization and antibacterial activity.
AB  - Metal(II) coordination compounds of a hydrazone ligand (HL) derived from the
      condensation of cephalexin antibiotic with 2,6-diacetylpyridine bis(hydrazone)
      were synthesized. The hydrazone ligand and mononuclear [ML(H2O)2][PF6] (M(II)=Mn,
      Co, Ni, Zn) complexes were characterized by several techniques, including
      elemental and thermal analysis, molar conductance and magnetic susceptibility
      measurements, electronic, FT-IR, EPR and (1)H NMR spectral studies. The
      cephalexin 2,6-diacetylpyridine bis(hydrazone) ligand HL behaves as a monoanionic
      tetradentate NNNO chelating agent. The biological applications of complexes have
      been studied on two bacteria strains (Escherichia coli and Staphylococcus aureus)
      by agar diffusion disc method. 

PMID- 25942082
TI  - Validation of four different spectrophotometric methods for simultaneous
      determination of Domperidone and Ranitidine in bulk and pharmaceutical
      formulation.
AB  - Four simple, specific, accurate and precise spectrophotometric methods were
      developed and validated for simultaneous determination of Domperidone (DP) and
      Ranitidine Hydrochloride (RT) in bulk powder and pharmaceutical formulation. The
      first method was simultaneous ratio subtraction (SRS), the second was ratio
      subtraction (RS) coupled with zero order spectrophotometry (D(0)), the third was
      first derivative of the ratio spectra ((1)DD) and the fourth method was mean
      centering of ratio spectra (MCR). The calibration curve is linear over the
      concentration range of 0.5-5 and 1-45 MUg mL(-1) for DP and RT, respectively. The
      proposed spectrophotometric methods can analyze both drugs without any prior
      separation steps. The selectivity of the adopted methods was tested by analyzing
      synthetic mixtures of the investigated drugs, also in their pharmaceutical
      formulation. The suggested methods were validated according to International
      Conference of Harmonization (ICH) guidelines and the results revealed that; they
      were precise and reproducible. All the obtained results were statistically
      compared with those of the reported method, where there was no significant
      difference.

PMID- 25942083
TI  - Surface-enhanced Raman scattering (SERS) study of anthocyanidins.
AB  - Anthocyanins are an important class of natural compounds responsible for the red,
      purple and blue colors in a large number of flowers, fruits and cereal grains.
      They are polyhydroxy- and polymethoxy-derivatives of 2-phenylbenzopyrylium
      (flavylium) salts, which are present in nature as glycosylated molecules. The aim
      of the present study is to assess the identification of anthocyanidins, i.e.
      anthocyanins without the glycosidic moiety, by means of surface-enhanced Raman
      spectroscopy (SERS), a very chemically-specific technique which is moreover
      sensitive to subtle changes in molecular structures. These features can lead to
      elect SERS, among the spectroscopic tools currently at disposal of scientists, as
      a technique of choice for the identification of anthocyanidins, since: (1)
      anthocyanidins structurally present the same benzopyrylium moiety and
      differentiate only for the substitution pattern on their phenyl ring, (2)
      different species are present in aqueous solution depending on the pH. It will be
      demonstrated that, while resonance Raman spectra of anthocyanidins are very
      similar to one another, SER spectra show greater differences, leading to a
      further step in the identification of such important compounds in diluted
      solutions by means of vibrational spectroscopy. Moreover, the dependence on the
      pH of the six most common anthocyanidins, i.e. cyanidin, delphinidin,
      pelargonidin, peonidin, malvidin and petunidin, is studied. To the best of the
      authors' knowledge, a complete SERS study of such important molecules is reported
      in the present work for the first time. 

PMID- 25942084
TI  - Pure white OLED based on an organic small molecule: 2,6-Di(1H-benzo[d]imidazol-2
      yl)pyridine.
AB  - 2,6-Di(1H-benzo[d]imidazol-2-yl)pyridine (DBIP) was synthesized. The single
      crystal structure of DBIP was resolved. DBIP-based OLED was fabricated. The
      electroluminescence for the device corresponds to a pure white emission. In
      addition, thermal stability, UV-vis, photoluminescence and electrochemical
      behaviors of DBIP were investigated as well. 

PMID- 25942085
TI  - Ultrafast imaging of electronic relaxation in n-propylbenzene: Direct observation
      of intermediate state.
AB  - The ultrafast dynamics of the second singlet electronically excited state (S2) in
      n-propylbenzene has been investigated by femtosecond time-resolved photoelectron
      imaging coupled with photofragmentation spectroscopy. The intermediate state for
      the deactivation of the S2 state is observed by transient photoelectron kinetic
      energy distributions and photoelectron angular distributions. An ultrafast
      electronic relaxation process on timescale of the fitted ~50 fs was observed in
      the S2 state by time-resolved photoelectron imaging and it is attributed to the
      S1<-S2 internal conversion (IC). The time constant of 1.23 (+/-0.2) ps is
      determined for the further deactivation of the intermediate S1 state.

PMID- 25942086
TI  - Spectroscopic and statistical approach of archaeological artifacts recently
      excavated from Tamilnadu, South India.
AB  - The ancient materials characterization will bring back the more evidence of the
      ancient people life styles. In this study, the archaeological pottery shards
      recently excavated from Kodumanal, Erode District in Tamilnadu, South India were
      investigated. The experimental results enlighten us to the elemental and the
      mineral composition of the pottery shards. The FT-IR technique tells that the
      mineralogy and the firing temperature of the samples are less than 800  degrees
      C, in the oxidizing/reducing atmosphere and the XRD was used as a complementary
      technique for the mineralogy. A thorough scientific study of SEM-EDS with the
      help of statistical approach done to find the provenance of the selected pot
      shards has not yet been performed. EDS and XRF results revealed that the
      investigated samples have the elements O, Si, Al, Fe, Mn, Mg, Ca, Ti, K and Na
      are in different compositions. For establishing the provenance (same or different
      origin) of pottery samples, Al and Si concentration ratio as well as hierarchical
      cluster analysis (HCA) was used and the results are correlated.

PMID- 25942087
TI  - A direct method of quantification of maximal chemisorption of 3-aminopropylsilyl
      groups on silica gel using DRIFT spectroscopy.
AB  - 3-Aminopropylsilyl (APS) modified silica gel plays an important role as a
      precursor for further modifications, where APS acts as a spacer or bridging
      molecule. A monolayer of APS which is most suitable for this purpose was obtained
      in anhydrous conditions. The properties of the APS-modified silica gel depend on
      the amount of molecules chemisorbed on the surface. A direct quantitative method
      using Diffuse Reflectance Infrared Fourier Transform (DRIFT) spectroscopy was
      proposed. The obtained results were further supported by elemental analysis. The
      conclusion was that the proposed methodology can be used for the quantification
      of APS groups chemisorbed on silica gel when the grafting chemical reaction was
      mainly irreversible. 

PMID- 25942088
TI  - Charge-transfer complexes of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone with amino
      molecules in polar solvents.
AB  - The charge-transfer complexes have scientific relevance because this type of
      molecular interaction is at the basis of the activity of pharmacological
      compounds and because the absorption bands of the complexes can be used for the
      quantification of electron donor molecules. This work aims to assess the
      stability of the charge-transfer complexes between the electron acceptor 2,3
      dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and two drugs, procaine and atenolol,
      in acetonitrile and ethanol. The stability of DDQ in solution and the time
      required to obtain the maximum complex formation were evaluated. The
      stoichiometry and the stability of the complexes were determined, respectively,
      by Job's plot method and by the elaboration of UV-vis titrations data. The latter
      task was carried out by using the non-linear global analysis approach to
      determine the equilibrium constants. This approach to data elaboration allowed us
      to overcome the disadvantages of the classical linear-regression method, to
      obtain reliable values of the association constants and to calculate the entire
      spectra of the complexes. NMR spectra were recorded to identify the portion of
      the donor molecule that was involved in the interaction. The data support the
      participation of the aliphatic amino groups in complex formation and exclude the
      involvement of the aromatic amine present in the procaine molecule. 

PMID- 25942089
TI  - Solvent-dependent "turn-on" fluorescence chemosensor for Mg(2+) based on
      combination of C=N isomerization and inhibition of ESIPT mechanisms.
AB  - A fluorescent chemosensor (L) for Mg(2+) has been synthesized and characterized,
      which exhibits turn-on fluorescence response for Mg(2+) only in alcohol solvent
      (methanol or ethanol) with high sensitivity and selectivity. But in both nonpolar
      and polar solvents (cyclohexane, DCM, DMSO or MeCN), L showed negligible
      fluorescent response for Mg(2+). In order to discover the unique phenomenon,
      optical measurements, liquid chromatography coupled with tandem mass spectrometry
      (LC-MS/MS) and a high performance liquid chromatography with a fluorescence
      detector (HPLC-FLD) of L and L with Mg(2+) ions in solvents were studied. In
      alcohol solvent, [L+alcohol molecule] was formed and the mechanism aspect of L
      concerning the remarkable fluorescence response for Mg(2+) has been discussed. 

PMID- 25942090
TI  - A new chalcone structure of (E)-1-(4-Bromophenyl)-3-(napthalen-2-yl)prop-2-en-1
      one: Synthesis, structural characterizations, quantum chemical investigations and
      biological evaluations.
AB  - The structure of (E)-1-(4-Bromophenyl)-3-(napthalen-2-yl)prop-2-en-1-one
      (C19H13BrO) crystallized in the triclinic system of P-1 space group. The unit
      cell dimensions are: a=5.8944 (9)A, b=7.8190 (12)A, c=16.320 (2)A, alpha=102.4364
      (19) degrees , beta=95.943 (2) degrees , gamma=96.274 (2) degrees  and Z=2. The
      physical properties of this compound was determined by the spectroscopic methods
      (FTIR and (1)H and (13)C NMR). Quantum chemical investigations have been employed
      to investigate the structural and spectral properties. The molecular structure,
      vibrational assignments, (1)H and (13)C NMR chemical shift values, non-linear
      optical (NLO) effect, HOMO-LUMO analysis and natural bonding orbital (NBO)
      analysis were calculated using HF and DFT/B3LYP methods with 6-311++G(d,p) basis
      set in the ground state. The results show that the theoretical calculation of the
      geometrical parameters, vibrational frequencies and chemical shifts are
      comparable with the experimental data. The crystal structure is influenced and
      stabilized by weak C-H?pi interactions connecting the molecules into infinite
      supramolecular one dimensional ladder-like arrangement. Additionally, this
      compound is evaluated for their antibacterial activities against gram positive
      and gram negative strains using a micro dilution procedure and shows activities
      against a panel of microorganisms. 

PMID- 25942091
TI  - Visual detection of trace copper ions based on copper-catalyzed reaction of
      ascorbic acid with oxygen.
AB  - A visual detection method for trace Cu(2+) in aqueous solutions using triangular
      silver nanoplates (abbreviated as TAgNPs) as the probe was developed. The method
      is based on that TAgNPs could be corroded in sodium thiosulfate (Na2S2O3)
      solutions. The absorption spectrum of TAgNPs solution changed when it is corroded
      by Na2S2O3. The reaction of oxygen with ascorbic acid (Vc) in the presence of a
      low concentration of Cu(2+) generates hydrogen peroxide that reacts with Na2S2O3,
      which leads the concentration of Na2S2O3 in the solution to be decreased.
      Therefore, the reaction between TAgNPs and the reacted mixture of
      Na2S2O3/Vc/Cu(2+) was prevented efficiently. When the Na2S2O3 concentration and
      reaction time are constant, the decrease in the concentration of Na2S2O3 is
      directly proportional to the Cu(2+) concentration. Thus, morphology, color, and
      maximum absorption wavelength of TAgNPs changed with the change of Cu(2+)
      concentration. The changed maximum absorption wavelength of TAgNPs (Deltalambda)
      is proportional to Cu(2+) concentration in the range from 7.5*10(-9) to 5.0*10(
      7) M with a correlation coefficient of r=0.9956. Moreover, color change of TAgNP
      solution was observed clearly over a Cu(2+) concentration range from 7.5*10(-8)
      to 5.0*10(-7) M. This method has been used to detect the Cu(2+) content of a
      human hair sample, and the result is in agreement with that obtained by the
      atomic absorption spectroscopy (AAS) method.

PMID- 25942092
TI  - Dereplication and chemotaxonomical studies of marine algae of the Ochrophyta and
      Rhodophyta phyla.
AB  - Dereplication and chemotaxonomic studies of six marine algae of the Ochrophyta
      and one of the Rhodophyta phyla resulted in the detection of 22 separate
      compounds. All 16 secondary metabolites, including four new compounds (16-19),
      could be rapidly dereplicated using HPLC-NMR and HPLC-MS methodologies in
      conjunction with the MarinLit database. This study highlights the advantages of
      using NMR data (acquired via HPLC-NMR) for database searching and for the overall
      dereplication of natural products. 

PMID- 25942093
TI  - Anti-obese effect of glucosamine and chitosan oligosaccharide in high-fat diet
      induced obese rats.
AB  - OBJECTIVE: This study is to evaluate the anti-obese effects of glucosamine (GLC)
      and chitosan oligosaccharide (COS) on high-fat diet-induced obese rats. METHODS:
      The rats were randomly divided into twelve groups: a normal diet group (NF), a
      high-fat diet group (HF), Orlistat group, GLC high-, middle-, and low-dose groups
      (GLC-H, GLC-M, GLC-L), COS1 (COS, number-average molecular weight <=1000) high-,
      middle-, and low-dose groups (COS1-H, COS1-M, COS1-L), and COS2 (COS, number
      average molecular weight <=3000) high-, middle-, and low-dose groups (COS2-H,
      COS2-M, COS2-L). All groups received oral treatment by gavage once daily for a
      period of six weeks. RESULTS: Rats fed with COS1 gained the least weight among
      all the groups (P < 0.01), and these rats lost more weight than those treated
      with Orlistat. In addition to the COS2-H and Orlistat groups, the serum total
      cholesterol (CHO) and low-density lipoprotein cholesterol (LDL-C) levels were
      significantly reduced in all treatment groups compared to the HF group (P <
      0.01). The various doses of GLC, COS1 and COS2 reduced the expression levels of
      PPARgamma and LXRalpha mRNA in the white adipose tissue. CONCLUSIONS: The results
      above demonstrated that GLC, COS1, and COS2 improved dyslipidemia and prevented
      body weight gains by inhibiting the adipocyte differentiation in obese rats
      induced by a high-fat diet. Thus, these agents may potentially be used to treat
      obesity.

PMID- 25942095
TI  - Facile synthesis of CuO nanosheets via the controlled delamination of layered
      copper hydroxide acetate.
AB  - CuO nanosheets were prepared by the controlled delamination of layered copper
      hydroxide acetate followed by the in situ solvothermal transformation of
      hydroxide to oxide. The reaction was performed in 1-butanol in order to prevent
      recrystallization or nanoparticle aggregation. Analyses by small angle X-ray
      scattering, transmission electron microscopy, and atomic force microscopy
      revealed that the CuO nanosheets are approximately 1 nm thin, corresponding to
      three to four stacked CuO6 octahedral layers. The average lateral size is
      approximately 5 nm. The nanosheets form stable dispersions in 1-butanol that are
      suitable for the fabrication of transparent and homogeneous CuO thin films by
      spin-coating or inkjet printing techniques. The present synthesis is a rare
      example of the top down strategy leading to the nanometric two-dimensional
      nanosheets of non-layered oxide materials.

PMID- 25942094
TI  - Eunicellin-Based Diterpenoids, Hirsutalins S-V, from the Formosan Soft Coral
      Cladiella hirsuta.
AB  - Four new eunicellin-type hirsutalins S-V (1-4), along with a known compound (-)
      6alpha-hydroxy polyanthellin A (5), were isolated from the soft coral Cladiella
      hirsuta. The structures of the metabolites were determined by extensive
      spectroscopic analysis. Cytotoxity of compounds 1-5 against the proliferation of
      a limited panel of cancer cell lines was measured. Anti-inflammatory activity of
      compounds 1-5 was evaluated by measuring their ability in suppressing superoxide
      anion generation and elastase release in fMLP/ CB-induced human neutrophils. 

PMID- 25942096
TI  - Protein attachment to silane-functionalized porous silicon: A comparison of
      electrostatic and covalent attachment.
AB  - Porous silicon (pSi) is a prosperous biomaterial, biocompatible, and
      biodegradable. Obtaining regularly functionalized pSi surfaces is required in
      many biotechnology applications. Silane-PEG-NHS (triethoxysilane-polyethylene
      glycol-N-hydroxysuccinimide) is useful for single-molecule studies due to its
      ability to attach to only one biomolecule. We investigate the functionalization
      of pSi with silane-PEG-NHS and compare it with two common grafting agents: APTMS
      (3-aminopropylotrimethoxysilane) as electrostatic linker, and APTMS modified with
      glutaraldehyde as covalent spacer. We show the arrangement of two proteins
      (collagen and bovine serum albumin) as a function of the functionalization and of
      the pore size. FTIR is used to demonstrate correct functionalization while
      fluorescence confocal microscopy reveals that silane-PEG-NHS results in a more
      uniform protein distribution. Reflection interference spectroscopy (RIfS) is used
      to estimate the attachment of linker and proteins. The results open a way to
      obtain homogenous chemical modified silicon supports with a great value in
      biosensing, drug delivery and cell biology. 

PMID- 25942097
TI  - Layer-by-layer introduction of poly(phenylenevinylene) onto microspheres and
      probing the influence from the weak/strong polyanion spacer-layers.
AB  - The layer-by-layer (LBL) technique was employed for preparing fluorescent
      microspheres with a core-shell structure by the alternating adsorption of
      positively charged poly(p-phenylenevinylene) precursor (pre-PPV) and the
      polyanions onto polymer substrate spheres, followed by the thermal elimination to
      convert pre-PPV into fluorescent poly(p-phenylenevinylene) (PPV). Weak
      polyelectrolytes poly(acrylic acid) (PAA) (usually in a partly ionized form) and
      strong polyelectrolytes poly(sodium-p-styrenesulfonate) (PSS) were used as the
      anions to space the PPV layers and reduce the fluorescence self-quenching. Flow
      cytometry, combined with spectroscopy and microscopy, were used to study the
      structure and photophysical properties of the resulting microspheres.
      Optimization of the processing factors was carried out. PAA and PSS as weak and
      strong polyelectrolytes, respectively, displayed very different influence on the
      final emission of the spheres. Such difference was attributed to different
      inherent characteristics of PAA and PSS after detailed investigation in many
      aspects. In addition, the fluorescent spheres were found to have excellent
      photostability and thermal stability. 

PMID- 25942098
TI  - Microwave-assisted preparation of N-doped carbon dots as a biosensor for
      electrochemical dopamine detection.
AB  - A new N-doped carbon dots (NCDs) could be prepared by using the microwave
      assisted technique within 10 min without the need for any solvent or catalyst.
      The NCDs exhibited a highly sensitive electrochemical response toward dopamine
      (DA) in Phosphate Buffered Saline (PBS) (pH=6.5). The detection limit of DA was
      calculated by differential pulse voltammetry (DPV) as low as 1.2*10(-9) mol/L
      with a linear dynamic range of 5.0*10(-8) to 8.0*10(-6) mol/L. These results
      suggested that this new NCDs could be effectively used for the direct and rapid
      detection of trace levels of DA in human serum and urine samples.

PMID- 25942099
TI  - Loss of CDK5RAP2 affects neural but not non-neural mESC differentiation into
      cardiomyocytes.
AB  - Biallelic mutations in the gene encoding centrosomal CDK5RAP2 lead to autosomal
      recessive primary microcephaly (MCPH), a disorder characterized by pronounced
      reduction in volume of otherwise architectonical normal brains and intellectual
      deficit. The current model for the microcephaly phenotype in MCPH invokes a
      premature shift from symmetric to asymmetric neural progenitor-cell divisions
      with a subsequent depletion of the progenitor pool. The isolated neural
      phenotype, despite the ubiquitous expression of CDK5RAP2, and reports of
      progressive microcephaly in individual MCPH cases prompted us to investigate
      neural and non-neural differentiation of Cdk5rap2-depleted and control murine
      embryonic stem cells (mESC). We demonstrate an accumulating proliferation defect
      of neurally differentiating Cdk5rap2-depleted mESC and cell death of
      proliferative and early postmitotic cells. A similar effect does not occur in non
      neural differentiation into beating cardiomyocytes, which is in line with the
      lack of non-central nervous system features in MCPH patients. Our data suggest
      that MCPH is not only caused by premature differentiation of progenitors, but
      also by reduced propagation and survival of neural progenitors.

PMID- 25942100
TI  - Effects of DHA-rich fish oil supplementation on the lipid profile, markers of
      muscle damage, and neutrophil function in wheelchair basketball athletes before
      and after acute exercise.
AB  - We investigated the effects of docosahexaenoic acid (DHA)-rich fish oil (FO)
      supplementation on the lipid profile, levels of plasma inflammatory mediators,
      markers of muscle damage, and neutrophil function in wheelchair basketball
      players before and after acute exercise. We evaluated 8 male basketball
      wheelchair athletes before and after acute exercise both prior to (S0) and
      following (S1) FO supplementation. The subjects were supplemented with 3 g of FO
      daily for 30 days. The following components were measured: the plasma lipid
      profile (total cholesterol, high-density lipoprotein cholesterol, low-density
      lipoprotein cholesterol, and triglycerides), plasma inflammatory mediators (C
      reactive protein, interleukin (IL)-1beta, IL-1ra, IL-4, IL-6, IL-8, and tumor
      necrosis factor-alpha), markers of muscle damage (creatine kinase and lactate
      dehydrogenase (LDH)), and neutrophil function (cytokine production, phagocytic
      capacity, loss of membrane integrity, mitochondrial membrane potential, neutral
      lipid accumulation, phosphatidylserine externalization, DNA fragmentation, and
      production of reactive oxygen species (ROS)). Acute exercise increased the plasma
      levels of total cholesterol, LDH, IL1ra, and IL-6, led to the loss of membrane
      integrity, ROS production, and a high mitochondrial membrane potential in
      neutrophils, and reduced the phagocytic capacity and IL-6 production by the
      neutrophils (S0). However, supplementation prevented the increases in the plasma
      levels of LDH and IL-6, the loss of membrane integrity, and the alterations in
      ROS production and mitochondrial membrane potential in the neutrophils that were
      induced by exercise (S1). In conclusion, DHA-rich FO supplementation reduces the
      markers of muscle damage, inflammatory disturbances, and neutrophil death induced
      by acute exercise in wheelchair athletes. 

PMID- 25942101
TI  - Contamination of food crops grown on soils with elevated heavy metals content.
AB  - The exposure of inhabitants from 13 cities of The Upper Silesia Industrial Region
      to cadmium and lead has been estimated on the basis of heavy metals content in
      commonly consumed vegetables. The samples were collected from agricultural
      fields, allotments and home gardens in these cities. Cadmium and lead
      concentrations in samples of soil and vegetables - cabbage, carrots and potatoes
      were determined. High content of heavy metals in the arable layer of soil in
      Upper Silesia (max. 48.8 and 2470mgkg(-1) d.w. for Cd and Pb, respectively)
      explained high Cd and Pb concentrations in locally cultivated vegetables which
      are well above the permissible level. Three exposure scenarios with different
      concentrations of Pb and Cd in vegetables were taken into consideration. In the
      Scenario I where the content of heavy metals was equal to maximum permissible
      level, the value of hazard quotient (HQ) for Pb and Cd was 0.530 and 0.704,
      respectively. In the scenarios where were assumed consumption of contaminated
      vegetables from Upper Silesia the value of hazard quotient (HQ) for Pb and Cd was
      0.755 and 1.337 for Scenario II and 1.806 and 4.542 for Scenario III. The study
      showed that consumption of vegetables cultivated in Upper Silesia Region on the
      agricultural fields, allotments and in home gardens may pose a significant health
      risk. 

PMID- 25942102
TI  - Heavy-metal resistance in Gram-negative bacteria isolated from Kongsfjord,
      Arctic.
AB  - Isolation and characterization of heterotrophic Gram-negative bacteria was
      carried out from the sediment and water samples collected from Kongsfjord,
      Arctic. In this study, the potential of Arctic bacteria to tolerate heavy metals
      that are of ecological significance to the Arctic (selenium (Se), mercury (Hg),
      cadmium (Cd), copper (Cu), lead (Pb), and zinc (Zn)) was investigated.
      Quantitative assay of 130 isolates by means of plate diffusion and tube dilution
      methods was carried out by incorporation of different concentrations of metals.
      Growth in Se and Pb at a concentration of 3000 MUg/L was significantly lower
      (P<=0.0001) than at 2000 MUg/L. The minimum inhibitory concentration for Cd and
      Hg was 50 MUg/L (P<=0.0001, F=264.23 and P<=0.0001, F=291.08, respectively) even
      though in the tube dilution test, Hg-containing tubes showed much less growth,
      revealing its superior toxicity to Cd. Thus, the level of toxicity of heavy
      metals was found to be in the order of Hg>Cd>Cu>Zn>Pb>Se. Multiple-metal
      resistant isolates were investigated for their resistance against antibiotics,
      and a positive correlation was observed between antibiotic and metal resistance
      for all the isolates tested. The resistant organisms thus observed might
      influence the organic and inorganic cycles in the Arctic and affect the
      ecosystem.

PMID- 25942103
TI  - Barcelona Conference on Epigenetics and Cancer: 50 years of histone acetylation.
AB  - The Barcelona Conference on Epigenetics and Cancer (BCEC) was held in Barcelona,
      Spain, on October 1(st) and 2(nd), 2014. The meeting was co-organized by the
      Cancer Epigenetics and Biology Program (PEBC-IDIBELL) and B.Debate, an initiative
      of Biocat, with the support of "la Caixa" Foundation. The scientific committee
      was comprised of leading scientists in the field of epigenetics: Dr. Manel
      Esteller, director of PEBC-IDIBELL, Dr. Alejandro Vaquero and Dr. Esteban
      Ballestar, from PEBC-IDIBELL, Juan Ausio from the University of Victoria
      (Canada), and Marcus Buschbeck, from the Institute of Predictive and Personalized
      Medicine of Cancer (IMPPC), as BCEC series coordinator. This meeting was the
      second edition of the BCEC series, which was launched by 5 leading Barcelonan
      institutes to bring together leading investigators in the fields of epigenetics
      and chromatin research. The topics discussed during the meeting included the
      current challenges, opportunities, and perspectives surrounding the study of
      histone modifications (focusing in acetylation), chromatin structure and gene
      expression, and the involvement of histone acetylation in physiology and
      diseases, such as cancer or neurological diseases. 

PMID- 25942104
TI  - Glucocorticosteroids do not impact directly growth rate and biomass of Rhizopus
      arrhizus (syn. R. oryzae) in vitro.
AB  - Glucocorticoid (GC) use is a common risk factor for invasive fungal infections.
      This is attributed to the complex dysregulation of immunity caused by GCs.
      However, studies have demonstrated increased growth with GC exposure for some
      molds, such as Aspergillus fumigatus and Exserohilum rostratum. No such data
      exist for Mucorales. Therefore, we investigated the influence of GC exposure on
      the growth of Rhizopus arrhizus (syn. R. oryzae) in different culture media and
      in different atmospheres. We measured continuous spore growth using
      spectrophotometry and biomass variations using XTT assay. We did not observe
      enhanced growth or biomass variation with any of the GCs regardless of the medium
      or conditions. These results support the existence of fungus-specific differences
      in the effect of GCs on fungal biology. 

PMID- 25942108
TI  - Officers and executive committee.

PMID- 25942109
TI  - Welcome from the chairman.

PMID- 25942110
TI  - The plastic surgery research council 59th annual meeting abstract supplement.

PMID- 25942111
TI  - Historical perspective: the plastic surgery research council.

PMID- 25942112
TI  - Abstract 1: What's the Best Way to Allocate or Block Time? A Data Driven Approach
      to Departmental "Operations".

PMID- 25942113
TI  - Abstract 2: NOTCH3 Regulates Mural Cell Differentiation of HemSCs.

PMID- 25942106
TI  - Minireview: Activin Signaling in Gonadotropes: What Does the FOX say... to the
      SMAD?
AB  - The activins were discovered and named based on their abilities to stimulate FSH
      secretion and FSHbeta (Fshb) subunit expression by pituitary gonadotrope cells.
      According to subsequent in vitro observations, activins also stimulate the
      transcription of the GnRH receptor (Gnrhr) and the activin antagonist,
      follistatin (Fst). Thus, not only do activins stimulate FSH directly, they have
      the potential to regulate both FSH and LH indirectly by modulating gonadotrope
      sensitivity to hypothalamic GnRH. Moreover, activins may negatively regulate
      their own actions by stimulating the production of one of their principal
      antagonists. Here, we describe our current understanding of the mechanisms
      through which activins regulate Fshb, Gnrhr, and Fst transcription in vitro. The
      activin signaling molecules SMAD3 and SMAD4 appear to partner with the winged
      helix/forkhead transcription factor, forkhead box L2 (FOXL2), to regulate
      expression of all 3 genes. However, in vivo data paint a different picture.
      Although conditional deletion of Foxl2 and/or Smad4 in murine gonadotropes
      produces impairments in FSH synthesis and secretion as well as in pituitary Fst
      expression, Gnrhr mRNA levels are either unperturbed or increased in these
      animals. Surprisingly, gonadotrope-specific deletion of Smad3 alone or with Smad2
      does not impair FSH production or fertility; however, mice harboring these
      mutations may express a DNA binding-deficient, but otherwise functional, SMAD3
      protein. Collectively, the available data firmly establish roles for FOXL2 and
      SMAD4 in Fshb and Fst expression in gonadotrope cells, whereas SMAD3's role
      requires further investigation. Gnrhr expression, in contrast, appears to be
      FOXL2, SMAD4, and, perhaps, activin independent in vivo.

PMID- 25942107
TI  - Minireview: Role of intracellular scaffolding proteins in the regulation of
      endocrine G protein-coupled receptor signaling.
AB  - The majority of hormones stimulates and mediates their signal transduction via G
      protein-coupled receptors (GPCRs). The signal is transmitted into the cell due to
      the association of the GPCRs with heterotrimeric G proteins, which in turn
      activates an extensive array of signaling pathways to regulate cell physiology.
      However, GPCRs also function as scaffolds for the recruitment of a variety of
      cytoplasmic protein-interacting proteins that bind to both the intracellular face
      and protein interaction motifs encoded by GPCRs. The structural scaffolding of
      these proteins allows GPCRs to recruit large functional complexes that serve to
      modulate both G protein-dependent and -independent cellular signaling pathways
      and modulate GPCR intracellular trafficking. This review focuses on GPCR
      interacting PSD95-disc large-zona occludens domain containing scaffolds in the
      regulation of endocrine receptor signaling as well as their potential role as
      therapeutic targets for the treatment of endocrinopathies. 

PMID- 25942114
TI  - Abstract 3: propranolol accelerates involution in a murine model of infantile
      hemangioma.

PMID- 25942115
TI  - Abstract 4: Site Specific Targeting of PUMA Induced ROS Prevents Radiation Injury
      via a Smad3 Independent Mechanism.

PMID- 25942116
TI  - Abstract 5: A 28-Day Prospective, Randomized, Double-Blind, Placebo Controlled
      Clinical Trial of Botulinum Toxin Type A for Raynaud's Phenomen.

PMID- 25942117
TI  - Abstract 6: The BREASTrial: Breast Reconstruction Evaluation of Acellular Dermal
      Matrix as a Sling Trial, Design and Stage I Outcomes of a Randomized Trial.

PMID- 25942118
TI  - Abstract 7: Bioprosthetic versus Synthetic Mesh for Reconstruction of Oncologic
      Chest Wall Defects.

PMID- 25942119
TI  - Abstract 8: SDF-1 Regulates Adipose Niche Homeostasis and Adipose Derived Stromal
      Cell Function.

PMID- 25942120
TI  - Abstract 9: selectively permeable nanofiber constructs to prevent inflammatory
      scarring and enhance nerve regeneration in peripheral nerve injury.

PMID- 25942121
TI  - Abstract 10: Global and Endothelial Cell Specific Deletion of SDF-1 Results in
      Delayed Wound Healing.

PMID- 25942122
TI  - Abstract 11: the role of donor antigen persistance in maintaining immune
      tolerance to a vascularized composite allograft.

PMID- 25942124
TI  - Abstract 13: Functional Analysis of Connective Tissue Growth Factor (ctgf) in
      Neural Crest And Craniofacial Development.

PMID- 25942123
TI  - Abstract 12: Achieving Tolerance in a Mismatched VCA Transplant While Reducing
      the Risk of GVHD: The Goal of Transient Chimerism.

PMID- 25942125
TI  - Abstract 14: requirement of specc1lb in facial prominence integration and
      formation of the lower jaw.

PMID- 25942126
TI  - Abstract 15: Characterization of the Endothelial Progenitor Cell from Adult
      Tissue using Vav/Cre RFP-GFP Murine Model and Single Cell Microfluidics.

PMID- 25942127
TI  - Abstract 16: The Analgesic Efficacy of the Transversus Abdominis Plane (TAP)
      Block on the Abdominal Donor Site Following Autologous Tissue Breast
      Reconstruction: A Double-Blind, Placebo-Controlled Randomized Trial.

PMID- 25942128
TI  - Abstract 17: prototype sensory regenerative peripheral nerve interface for
      artificial limb somatosensory feedback.

PMID- 25942129
TI  - Abstract 18: real-time proportional control of a neuroprosthetic hand by a rodent
      regenerative peripheral nerve interface.

PMID- 25942130
TI  - Abstract 19: the effect of whole body vibration on life expectancy, cell damage
      and inflammation in a murine model.

PMID- 25942131
TI  - Abstract 20: prediction of optimal proximal interphalangeal joint fusion angle
      using simulated joint arthrodesis.

PMID- 25942132
TI  - Abstract 21: frequency and impact of inappropriate emergent transfer for hand
      surgical consultation.

PMID- 25942133
TI  - Abstract 22: a portable handheld facial-grading device for unilateral facial
      paralysis following facial reanimation surgery: reproducibility and reliability.

PMID- 25942134
TI  - Abstract 23: Novel Antimicrobial Coating of Non-crosslinked Acellular Porcine
      Dermal Matrix Provides Protection from Microbial Colonization by Common
      Pathogenic Microorganisms in a Rabbit Model.

PMID- 25942135
TI  - Abstract 24: Bibliometric Indices and Academic Promotion within Plastic Surgery.

PMID- 25942136
TI  - Abstract 25: electrical impedance spectroscopy as a tool for analysis of in vivo
      encapsulation of muscle electrodes.

PMID- 25942138
TI  - Abstract 27: an evaluation of a novel craniofacial skills laboratory curriculum:
      an aid to plastic surgery resident milestone achievement in technical skills and
      instrument knowledge.

PMID- 25942137
TI  - Abstract 26: an engineered lipoproteoplex presents robust delivery mechanism for
      topical gene therapy.

PMID- 25942139
TI  - Abstract 28: effect of glabellar paralysis by botulinum toxin on ability to
      communicate emotion.

PMID- 25942140
TI  - Abstract 29: Evaluation of 3D Photographic Imaging as a Method to Measure
      Differential Volumes in Reconstructed Breast Tissue.

PMID- 25942141
TI  - Abstract 30: the economic implications of changing trends in breast flap
      reconstruction in the United States.

PMID- 25942142
TI  - Abstract 31: DNA methylation analysis of radiated skin reveals chonic
      inflammation with a predominance of polymorphonuclear granulocytes.

PMID- 25942143
TI  - Abstract 32: amifostine reduces radiation-induced complications in a murine model
      of expander-based breast reconstruction.

PMID- 25942144
TI  - Abstract 33: Stress Offloading through Mechanomodulation is Associated with Down
      Regulation of Inflammatory Pathways in a Large Animal Model.

PMID- 25942145
TI  - Abstract 34: a novel immune competent murine hypertrophic scar contracture model:
      a tool to elucidate disease mechanism and develop new therapies.

PMID- 25942146
TI  - Abstract 35: central role of early vascularization in burn and trauma-induced
      heterotopic ossification.

PMID- 25942147
TI  - Abstract 36: development of a novel lymphatic reporter mouse.

PMID- 25942148
TI  - Abstract 37: peripheral nerve repair: multimodal comparison of the regenerative
      potential of adipose tissue derived cells in a biodegradable conduit.

PMID- 25942149
TI  - Abstract 38: tracheal allotransplantation and prefabrication for long tracheal
      stenosis with withdrawal of immunosuppression: from bed to bench.

PMID- 25942150
TI  - Abstract 39: the pig as an ideal training model for perforator flap dissection in
      living tissue.

PMID- 25942151
TI  - Abstract 40: hernia repair with coriumflap? - vascularized!

PMID- 25942152
TI  - Abstract 41: increased anesthesia duration increases venous thromboembolism risk
      in plastic surgery: a six-year analysis of over 19,000 cases.

PMID- 25942153
TI  - Abstract 42: Risk Assessment of Concurrent Panniculectomy with Open Ventral
      Hernia Repair: A Propensity Score-Matched Analysis Using the 2005-2011 ACS-NSQIP.

PMID- 25942154
TI  - Abstract 43: Prophylactic Mastectomies: Implications of Occult Histology and
      Lifetime Cost of Surveillance vs. Surgery.

PMID- 25942155
TI  - Abstract 44: components separation for abdominal wall reconstruction: the pitt
      experience, a review of 605 cases.

PMID- 25942156
TI  - Abstract 45: broadening indications for immediate implant-based breast
      reconstruction.

PMID- 25942157
TI  - Abstract 46: The BRA Score: Creating a General Risk Calculator for Breast
      Reconstruction Outcomes.

PMID- 25942158
TI  - Abstract 47: surgical treatment of nipple malposition in nipple sparing
      mastectomy device-based reconstruction.

PMID- 25942159
TI  - Abstract 48: identification and the effective repair of the athletic hernia.

PMID- 25942160
TI  - Abstract 49: a retrospective review of plastic surgery consultations to evaluate
      the effect of web-based education on patient satisfaction and consultation time.

PMID- 25942161
TI  - Abstract 50: fabrication of tissue-engineered human constructs for patient
      specific auricles.

PMID- 25942162
TI  - Abstract 51: Decreased Secondary Bone Grafting but Poorer Midface Growth after
      Primary Alveolar Cleft Repair with Gingivoperiosteoplasty and rhBMP-2.

PMID- 25942163
TI  - Abstract 52: mutating fibroblast growth factor receptor 1 (fgfr1) in zebrafish to
      create a new model of craniosynostosis.

PMID- 25942164
TI  - Abstract 53: prophylactic amifostine preserves the biomechanical properties of
      irradiated bone in the murine mandible.

PMID- 25942165
TI  - Abstract 54: TGF Beta and BMP Signaling Pathways Influence Regenerative Capacity
      of Calvarial Bones via Cross-Talk and Modulation of Apoptosis: The Potential
      Therapeutic Role of Small Molecule Inhibitors of TGF Beta Signaling.

PMID- 25942166
TI  - Abstract 55: management of problematic infantile hemangioma using intralesional
      triamcinolone: efficacy and safety in 87 consecutive infants.

PMID- 25942167
TI  - Abstract 56: Differential Effects of Inflammatory Mediators TNFalpha, TGFbeta1 on
      Cellular Differentiation in a Primary Murine Muscle Cell in vitro Model of
      Heterotopic Ossification.

PMID- 25942168
TI  - Abstract 57: Evaluation of Cranial Bone Transport Distraction with and without
      Adipose Grafting.

PMID- 25942169
TI  - Abstract 58: management of pediatric condylar and subcondylar fractures: the
      algorithmal impact of concomitant mandibular arch fractures.

PMID- 25942170
TI  - Abstract 59: management of pediatric brachial plexus palsy: the role of nerve
      transfer combined with neurolysis or nerve grafting of the upper trunk.

PMID- 25942171
TI  - Abstract 60: Signal Strength, Reliability, and Validity of Active Regenerative
      Peripheral Nerve Interface Device Operation during Voluntary Movement.

PMID- 25942172
TI  - Abstract 61: Characterization of Regenerative Peripheral Nerve Device Signaling
      during Evoked Maximal and Submaximal Fatiguing Conditions.

PMID- 25942173
TI  - Abstract 62: development of an optogenetic sensory peripheral nerve interface.

PMID- 25942174
TI  - Abstract 63: senescent schwann cells inhibit nerve regeneration in a short
      conduit model.

PMID- 25942175
TI  - Abstract 64: epineural sheath jacket as a new surgical technique for neuroma
      prevention in the rat sciatic nerve model: a preliminary report.

PMID- 25942176
TI  - Abstract 65: Subclinical Peroneal Nerve Entrapment May be an Under-recognized
      Cause of Falls in Hospitalized Patients.

PMID- 25942177
TI  - Abstract 66: Single Treatment with Alpha-1-antitrypsin Enhances Nerve
      Regeneration After Peripheral Nerve Injury.

PMID- 25942178
TI  - Abstract 67: The Monoclonal Antibody Herceptin Improves Regeneration after
      Injured Nerves are Repaired Immediately or after a Period of Chronic Denervation.

PMID- 25942179
TI  - Abstract 68: Identification of twist Expression Patterns and Localized
      Manipulation of fgfr1 Expression in Zebrafish Cranial Sutures.

PMID- 25942180
TI  - Abstract 69: analysis of the role of wls in craniofacial development.

PMID- 25942181
TI  - Abstract 70: Propranolol Effects on Hemangiomas are Mediated via Distinct
      Pathways.

PMID- 25942182
TI  - Abstract 71: obesity-induced lymphedema: presentation, diagnosis, and management.

PMID- 25942183
TI  - Abstract 72: keratinocytes gene expression of innate and adaptative
      proinflammatory cytokines and members of the toll-like receptor pathways in
      severe burned.

PMID- 25942184
TI  - Abstract 73: MicroRNA Regulates Hemangioendothelioma Growth by Targeting the Nox
      4/MCP-1 Pathway.

PMID- 25942185
TI  - Abstract 74: characterization of the koliber mutant: a new model for
      craniosynostosis research.

PMID- 25942186
TI  - Abstract 75: expression of follicle-stimulating hormone receptor in vascular
      anomalies.

PMID- 25942187
TI  - Abstract 76: Modeling Craniosynostosis in Zebrafish using the Genome Editing
      Technique CRISPR.

PMID- 25942188
TI  - Abstract 77: TGF Beta is a Potent Inhibitor of BMP2 Mediated Osteogenic
      Differentiation in a Primary Murine Muscle Cell in vitro Model of Heterotopic
      Ossification.

PMID- 25942189
TI  - Abstract 78: An Experimental Study of Particulate Bone Graft for Secondary Inlay
      Cranioplasty over Scarred Dura.

PMID- 25942190
TI  - Abstract 79: deferoxamine in combination with adipose-derived stromal cells
      rescues mineralization and improves union rate in the treatment of established
      radiotherapy induced non-unions.

PMID- 25942191
TI  - Abstract 80: Parathyroid Hormone Remediates Radiation Damage in a Murine Model of
      Distraction Osteogenesis via Histological Evaluation.

PMID- 25942192
TI  - Abstract 81: BMP2 Stimulation of Adipose, Bone Marrow, and Muscle-Derived Stromal
      Cells Fails to Augment Calvarial Repair.

PMID- 25942193
TI  - Abstract 82: What is the Optimal Age for Cranial Vault Remodeling in Syndromic
      Craniosynostosis? Insights from the Johns Hopkins Experience.

PMID- 25942194
TI  - Abstract 83: improved biomechanical metrics in the treatment of radiotherapy
      induced non-unions with a novel combination therapy.

PMID- 25942195
TI  - Abstract 84: fractures of the mandibular condylar base are associated with severe
      blunt internal carotid artery injuries.

PMID- 25942196
TI  - Abstract 85: the role of distraction osteogenesis in the surgical management of
      craniosynostosis: a systematic review.

PMID- 25942197
TI  - Abstract 86: lymph node transplantation generates spontaneous lymphatic
      reconnection and restoration of lymphatic flow.

PMID- 25942198
TI  - Abstract 87: Beyond Cotton Candy: Fabrication of Capillary Networks within
      Biocompatible Tissue- Engineered Constructs from Kerria Lacca Resin (Shellac).

PMID- 25942199
TI  - Abstract 88: microvascular integration into versatile tissue engineering
      platforms.

PMID- 25942200
TI  - Abstract 89: Novel Targeting of the Alk-2 Receptor Using the Cre/lox System to
      Enhance Osseous Regeneration by Mesenchymal Stem Cells.

PMID- 25942201
TI  - Abstract 90: donor-recipient chimeric cell transplantation as a novel rescue
      therapy for acute radiation syndrome: a preliminary report.

PMID- 25942202
TI  - Abstract 91: Engineering Primary Schwann Cells using Lentiviruses to Control GDNF
      Expression.

PMID- 25942203
TI  - Abstract 92: skeletal muscle regeneration in a rat model with extracellular
      matrix and adipose derived stem cells.

PMID- 25942205
TI  - Abstract 94: decellularized porcine stomach extracellular matrix for tissue
      engineering and repair.

PMID- 25942204
TI  - Abstract 93: optimized repopulation of extracellular matrix hydrogel: synergistic
      effects of combinations of growth factors and adipoderived stem cells.

PMID- 25942206
TI  - Abstract 95: results of primary repair of submucous cleft palate with furlow
      palatoplasty in both syndromic and non-syndromic children.

PMID- 25942207
TI  - Abstract 96: the venous anastomotic flow-coupler for free flap monitoring: a
      prospective analysis of 85 microsurgical breast reconstruction cases.

PMID- 25942208
TI  - Abstract 97: timing and technical implications of breast reconstruction in anemic
      women: the advantages of staged (delayed-immediate) breast reconstruction.

PMID- 25942209
TI  - Abstract 98: nipple-sparing mastectomy in patients with previous breast surgery:
      comparative analysis of 123 immediate reconstructions.

PMID- 25942210
TI  - Abstract 99: reducing unplanned reoperations for mastectomy skin flap necrosis -
      a multidisciplinary approach.

PMID- 25942211
TI  - Abstract 100: Comparison of the Histological Characteristics of ADM Capsules to
      No-ADM Breast Capsules in ADM-Assisted Breast Reconstruction.

PMID- 25942212
TI  - Abstract 101: Intrathymic in Vivo Two-photon Microscopy Reveals the Interaction
      of Donor Bone Marrow-Derived Dendritic Cells and Host Thymocytes in a Model Of
      VCA Central Tolerance.

PMID- 25942213
TI  - Abstract 102: inflammatory mediators modulate alloreactive T cell susceptibility
      to immune-regulation in reconstructive transplantation.

PMID- 25942214
TI  - Abstract 103: primed mesenchymal stem cells prevent endothelial activation and
      improve allograft perfusion following transplantation.

PMID- 25942215
TI  - Abstract 104: MHC class I sharing influences the fate of the epidermal component
      of vascularized composite allografts in mixed chimerism based tolerance protocols
      in miniature Swine.

PMID- 25942216
TI  - Abstract 105: a non-suture cuff technique for lymph-vein anastomosis in a rat
      model.

PMID- 25942217
TI  - Abstract 106: Development of a Chimeric Free Flap Allograft Using the LGR6+
      Epithelial Stem Cell.

PMID- 25942218
TI  - Abstract 107: Deferoxamine Mitigates Radiation-Induced Hypovascularity and
      Improves Tissue Elasticity in a Rat Irradiated TRAM Flap Model.

PMID- 25942219
TI  - Abstract 108: photochemical tissue passivation for prevention of vein graft
      intimal hyperplasia.

PMID- 25942220
TI  - Abstract 109: venous flow monitoring using an entirely implanted, wireless
      Doppler sensor.

PMID- 25942221
TI  - Abstract 110: The Impact of Deferoxamine on Vascularity and Soft Tissue
      Biomechanics in a Rat TRAM Flap Model.

PMID- 25942222
TI  - Abstract 111: An Alternative to the SGAP Flap in Autologous Breast
      Reconstruction: The Gluteal Upper Lateral Flap (GULF).

PMID- 25942223
TI  - Abstract 112: Hydrogen Peroxide Priming of Cadaveric Veins Reveals the Underlying
      Anatomical Basis for Venous Complications of DIEP, TRAM and Other Flaps of the
      Anterior Torso.

PMID- 25942224
TI  - Abstract 113: Comparison of Outcomes for Patients Undergoing Free Flap Autologous
      Breast Reconstruction Utilizing a Multimodal Enhanced Recovery Pathway versus
      Traditional Care.

PMID- 25942225
TI  - Abstract 114: use of morphomic analysis for preoperative risk stratification in
      patients undergoing major head and neck cancer surgery.

PMID- 25942226
TI  - Abstract 115: Combined Free Tissue Transfer For The Management Of Composite
      Achilles Defects: Functional Outcomes And Patient Satisfaction Following
      Vascularized Reconstruction With A Neo-tendon Construct.

PMID- 25942227
TI  - Abstract 116: the rate of oronasal fistula formation following primary cleft
      palate surgery: a meta-analysis.

PMID- 25942228
TI  - Abstract 117: Preoperative Anemia Increases the Risk of Adverse Outcomes in
      Patients Undergoing Free Tissue Transfer: a Critical Analysis of 2135 Patients
      from the ACS-NSQIP Database.

PMID- 25942229
TI  - Abstract 118: mastectomy weight and tissue expander fill volume predict skin
      necrosis and increased costs associated with breast reconstruction.

PMID- 25942230
TI  - Abstract 119: Validation of Clinical Criteria for Obtaining Maxillofacial CT in
      Trauma Patients.

PMID- 25942231
TI  - Abstract 120: Neoadjuvant Radiotherapy is not associated with Increased Post
      Mastectomy/Reconstruction Morbidity Events: A Critical Analysis of 85,851
      Patients from the ACS-NSQIP Database.

PMID- 25942232
TI  - Abstract 121: Evaluation of Otology Outcomes After Surgical Treatment of
      Symptomatic Pierre Robin Sequence: A Cohort Comparison Study Between Furlow
      Palatoplasty vs. Radical Intravelar Veloplasty.

PMID- 25942233
TI  - Abstract 122: prevalence and management of preoperative depression and anxiety
      disorders in patients undergoing mastectomy reconstruction.

PMID- 25942234
TI  - Abstract 123: Early Surgical Site Infection Following Tissue Expander Breast
      Reconstruction With And Without Acellular Dermal Matrix: National Benchmarking
      Using NSQIP.

PMID- 25942235
TI  - Abstract 124: outcomes of total skin-sparing mastectomy and reconstruction in 924
      breasts over 11 years.

PMID- 25942236
TI  - Abstract 125: adipogenesis by external volume expansion.

PMID- 25942237
TI  - Abstract 126: complication rates of fat grafting associated with various
      modalities of breast reconstruction.

PMID- 25942238
TI  - Abstract 127: Expression of SDF-1alpha in Skin Can be Upregulated by Mechanical
      Stretch and Induce Migration of Bone Marrow-Derived Stem Cells into Expanded
      Skin.

PMID- 25942239
TI  - Abstract 128: developing tumor-suppressing autologous fat grafts for breast
      cancer survivors.

PMID- 25942240
TI  - Abstract 129: Phosphodiesterase Type 5 Inhibition Enhances The Angiogenic Profile
      Of Adipose-derived Stem Cells.

PMID- 25942241
TI  - Abstract 130: Platelet-Rich Plasma Promotes Fat Graft Survival via Stemness and
      Angiogenesis on Adipose-derived Stem Cells.

PMID- 25942242
TI  - Abstract 131: Adipose Derived Stem Cell Count is Influenced by Receipt of
      Chemotherapy in Breast Cancer Patients.

PMID- 25942243
TI  - Abstract 132: the key components of schwann cell differentiation medium and the
      effects on the gene expression profile of adipose derived stem cells.

PMID- 25942244
TI  - Abstract 133: gender differences in heterotopic ossification.

PMID- 25942245
TI  - Abstract 134: Adipose Derived Stem Cells Express von Willebrand Factor and Factor
      VIII.

PMID- 25942246
TI  - Abstract 135: improved engraftment of autologous skin grafts in diabetic mice
      with adipose-derived stem cells.

PMID- 25942247
TI  - Abstract 136: Centrifugation Compared to a Combined Mesh/telfa Technique for Fat
      Grafting: Mechanism, Outcomes and Effect on ADSCs.

PMID- 25942248
TI  - Abstract 137: negative pressure wound therapy with instillation accelerates the
      granulation response with gene expression variations while maintaining comparable
      tissue quality compared to continuous and non-continuous negative pressure wound
      therapy in a porcine model.

PMID- 25942249
TI  - Abstract 138: Staphyloccocus aureus Biofilms Impair Reepithelialization and
      Granulation Tissue Deposition in Cutaneous Wounds via a MyD88-Dependent
      Mechanism.

PMID- 25942250
TI  - Abstract 139: macrophages regulate tissue fibrosis in lymphedema.

PMID- 25942251
TI  - Abstract 140: identification, characterization, and prospective isolation of a
      fibroblast lineage contributing to dermal development, cutaneous scarring,
      radiation fibrosis, and cancer stroma.

PMID- 25942252
TI  - Abstract 141: influence of MAPK signaling on ischemic wound healing in the
      elderly.

PMID- 25942253
TI  - Abstract 142: Prevention of Seroma and Post-operative Wound Complications Using
      Negative Pressure Wound Therapy Devices Following Panniculectomy in Massive
      Weight-Loss Patients.

PMID- 25942254
TI  - Abstract 143: morphologic and histological comparison of hypertrophic scar in
      nude and knockout mice deficient in T, B and natural killer cells.

PMID- 25942255
TI  - Abstract 144: cd4+ cells are key regulators of pathologic changes in lymphedema.

PMID- 25942256
TI  - Abstract 145: human keratinocytes have two distinct cell proliferation patterns
      on timelapse imaging in vitro with 8-cell microarrays revealing early molecular
      identifiers.

PMID- 25942257
TI  - Abstract 146: diet-induced obesity results in lymphatic dysfunction and impaired
      T cell function.

PMID- 25942258
TI  - Abstract 148: use of bmp type I alk-3 knockout mice to develop novel treatment
      strategies for trauma-induced heterotopic ossification.

PMID- 25942259
TI  - Abstract 149: effect of low energy laser on skin flap survival: a study in murine
      dorsal skin flap model.

PMID- 25942260
TI  - Abstract 150: Local Mild Hypothermia (30-32 degrees C) is Effective in Protection
      of Ex Vivo Human Skeletal Muscle from Hypoxia/Reoxygenation Injury.

PMID- 25942261
TI  - Abstract 151: short hairpin RNA interference therapy for diabetic murine wound
      closure and hindlimb ischemia.

PMID- 25942262
TI  - Abstract 152: pharmacologic inhibition of phosphodiesterase 5 as a strategy to
      improve outcomes in microvascular surgery.

PMID- 25942263
TI  - Abstract 153: A Novel 3D Platform to Investigate Neoangiogenesis,
      Transendothelial Migration and Metastasis of Breast Cancer Cells.

PMID- 25942264
TI  - Abstract 154: the anti-neoplastic effect of aminosterol squalamine on melanoma.

PMID- 25942266
TI  - Abstract 156: plastic surgery - quo vadis? Current trends and future projections
      of aesthetic plastic surgical procedures in the United States of america.

PMID- 25942265
TI  - Abstract 155: do unclothed images affect decision making in a conjoint analysis?

PMID- 25942267
TI  - Abstract 157: in vivo evaluation of a novel suture design for abdominal wall
      closure.

PMID- 25942268
TI  - Abstract 158: Identification of BMP-Responsive Long Noncoding RNAs in Pluripotent
      Cells.

PMID- 25942269
TI  - Abstract 159: SPY Imaging Use in Post-mastectomy Breast Reconstruction Patients:
      Preventative or Overly Conservative?

PMID- 25942270
TI  - Abstract 160: Biomechanical Considerations in Abdominal Wall Reconstruction using
      the Extended Component Separation Technique.

PMID- 25942271
TI  - Abstract 161: identification of cell-intrinsic mechanisms and differentially
      regulated genetic pathways responsible for the age-related functional decline in
      aged skeletal stem cells.

PMID- 25942272
TI  - Abstract 162: in vivo microanastomosis of microvessel containing tissue
      engineered constructs: the final frontier.

PMID- 25942273
TI  - Abstract 163: regional inflammation following lymph node transfer improves
      spontaneous lymphatic reconnection and functional drainage.

PMID- 25942274
TI  - Abstract 164: repair of critical size bone defects using bone marrow stromal
      cells a histomorphometric study in rabbit calvaria.

PMID- 25942275
TI  - Abstract 165: Enhanced Adipose-Derived Stromal Cell Osteogenesis through Surface
      Marker Enrichment and BMP Modulation using Magnet-assisted Transfection.

PMID- 25942278
TI  - Membership information.

PMID- 25942276
TI  - Abstract 166: electrospun synthetic scaffolds: a biomimetic approach to prevent
      hypertrophic scar contraction.

PMID- 25942279
TI  - Disclaimer.

PMID- 25942280
TI  - Stabilizing divalent europium in aqueous solution using size-discrimination and
      electrostatic effects.
AB  - We report two macrocyclic ligands containing a 1,10-diaza-18-crown-6 fragment
      functionalized with either two picolinamide pendant arms (bpa18c6) or one
      picolinamide and one picolinate arm (ppa18c6(-)). The X-ray structure of
      [La(ppa18c6)(H2O)](2+) shows that the ligand binds to the metal ion using the six
      donor atoms of the crown moiety and the four donor atoms of the pendant arms, 11
      coordination being completed by the presence of a coordinated water molecule. The
      X-ray structure of the [Sr(bpa18c6)(H2O)](2+) was also investigated due to the
      very similar ionic radii of Sr(2+) and Eu(2+). The structure of this complex is
      very similar to that of [La(ppa18c6)(H2O)](2+), with the metal ion being 11
      coordinated. Potentiometric measurements were used to determine the stability
      constants of the complexes formed with La(3+) and Eu(3+). Both ligands present a
      very high selectivity for the large La(3+) ion over the smaller Eu(3+), with a
      size-discrimination ability that exceeds that of the analogous ligand containing
      two picolinate pendant arms reported previously (bp18c6(2-)). DFT calculations
      using the TPSSh functional and the large-core pseudopotential approximation
      provided stability trends in good agreement with the experimental values,
      indicating that charge neutral ligands derived from 1,10-diaza-18-crown-6 enhance
      the selectivity of the ligand for the large Ln(3+) ions. Cyclic voltammetry
      measurements show that the stabilization of Eu(2+) by these ligands follows the
      sequence bp18c6(2-) < ppa18c6(-) < bpa18c6 with half-wave potentials of -753 mV
      (bp18c6(2-)), -610 mV (ppa18c6(-)), and -453 mV (bpa18c6) versus Ag/AgCl. These
      values reveal that the complex of bpa18c6 possesses higher stability against
      oxidation than the aquated ion, for which an E1/2 value of -585 mV has been
      measured. 

PMID- 25942281
TI  - Perovskite-Hematite Tandem Cells for Efficient Overall Solar Driven Water
      Splitting.
AB  - Photoelectrochemical water splitting half reactions on semiconducting
      photoelectrodes have received much attention but efficient overall water
      splitting driven by a single photoelectrode has remained elusive due to stringent
      electronic and thermodynamic property requirements. Utilizing a tandem
      configuration wherein the total photovoltage is generated by complementary
      optical absorption across different semiconducting electrodes is a possible
      pathway to unassisted overall light-induced water splitting. Because of the low
      photovoltages generated by conventional photovoltaic materials (e.g., Si, CIGS),
      such systems typically consist of triple junction design that increases the
      complexity due to optoelectrical trade-offs and are also not cost-effective.
      Here, we show that a single solution processed organic-inorganic halide
      perovskite (CH3NH3PbI3) solar cell in tandem with a Fe2O3 photoanode can achieve
      overall unassisted water splitting with a solar-to-hydrogen conversion efficiency
      of 2.4%. Systematic electro-optical studies were performed to investigate the
      performance of tandem device. It was found that the overall efficiency was
      limited by the hematite's photocurrent and onset potential. To understand these
      limitations, we have estimated the intrinsic solar to chemical conversion
      efficiency of the doped and undoped Fe2O3 photoanodes. The total photopotential
      generated by our tandem system (1.87 V) exceeds both the thermodynamic and
      kinetic requirements (1.6 V), resulting in overall water splitting without the
      assistance of an electrical bias. 

PMID- 25942282
TI  - A new furan derivative from an endophytic Aspergillus flavus of Cephalotaxus
      fortunei.
AB  - A new furan derivative named 5-acetoxymethylfuran-3-carboxylic acid (2), together
      with a known furan compound, 5-hydroxymethylfuran-3-carboxylic acid (1), were
      isolated from the fermentation of Aspergillus flavus, endophytic fungi in
      Cephalotaxus fortunei. The structures of 1 and 2 were elucidated by NMR, IR, UV
      and MS data, as well as compared with literature data. The compounds 1 and 2
      exhibited potent antibacterial activity against Staphylococcus aureus with MIC
      values of 31.3 and 15.6 MUg/mL, respectively. The compound 2 showed moderate
      antioxidant activity. 

PMID- 25942283
TI  - Group treatment for child sexual abuse: treatment referral and therapeutic
      outcomes.
AB  - A quasi-experimental design was used to compare the effectiveness of group (game
      based cognitive behavioral) therapy to group-plus-individual therapy for child
      sexual abuse. The sample consisted predominantly of children from economically
      disadvantaged, African-American or Latino backgrounds. Pretreatment scores were
      examined in order to determine which factors influence treatment referral
      decisions. Results suggest that children who were referred for individual therapy
      in addition to group therapy report higher pretreatment levels of sexualized
      behavior. Posttreatment differences were also compared across therapy conditions.
      Results suggest that individual therapy is needed to address the sexual concerns
      of survivors but that it may not be needed to augment the effects of group
      therapy for other symptoms. Implications for treatment are discussed. 

PMID- 25942284
TI  - Preservice teachers' sources of information on mandatory reporting of child
      sexual abuse.
AB  - Teachers in many countries are mandated by law, professional codes, or education
      authorities to report child abuse and neglect, including child sexual abuse.
      However, teachers may not receive adequate preparation for such sensitive
      interventions, as preservice teacher education degrees provide very few or no
      compulsory courses on child protection and crucially related, lifelong health and
      well-being issues. So, where do preservice teachers source their information
      regarding the mandatory reporting of such abuse? This research examines
      preservice teachers' professional university education for their sources of
      information about mandatory reporting and child sexual abuse. A sample cohort of
      56 final 4th-year university bachelor of education (primary school) student
      teachers in Australia identified the sources they used regarding 10 important
      aspects of child protection. The results suggest that most did not learn about
      mandatory reporting or child sexual abuse, and others cited sparse and sporadic
      public media as their primary information source. These findings, building on
      previous evidence about inadequate or nonexistent preservice mandatory
      intervention courses in primary teacher education, may guide the design of
      appropriate training responses enhancing educational professionals' knowledge,
      competencies, skills, and efficacies as mandatory reporters of child sexual
      abuse. 

PMID- 25942285
TI  - The NICHD Investigative Interview Protocol: A Meta-Analytic Review.
AB  - Systematic review and meta-analysis of literature were conducted examining the
      effectiveness of the National Institute for Child Health and Human Development
      Investigative Interview Protocol in improving the quality of child forensic
      interviews. Online databases were searched for journal articles published between
      the years 2000 and 2013. Measures of interview quality were the type of
      interviewer utterances and the amount of information provided by children. Five
      studies met criteria for inclusion in the meta-analysis. Weighted mean of the
      effect sizes was calculated for each outcome measure. Protocol interviews had
      more invitations (g = 1.60) and fewer option-posing (g = -.95) and suggestive
      prompts (g = -.63) than standard interviews. Children interviewed by the protocol
      provided more central details (g = .90) in response to invitations than controls.
      Meta-analyses of a subset of preschool children samples revealed that protocol
      interviews had more invitations (g = 1.46), fewer suggestive prompts (g = -.61),
      and fewer option-posing prompts (g = -1.05) than controls. Findings corroborate
      results from previous studies that suggested the benefits of the protocol on the
      interviewers' performance and on children's informativeness. However, protocol
      did not show the same performance with regard to preschool children. 

PMID- 25942286
TI  - A national survey of child advocacy center directors regarding knowledge of
      assessment, treatment referral, and training needs in physical and sexual abuse.
AB  - Mental health services are a core component of child advocacy centers in the
      United States. Child advocacy center directors were surveyed about (a) trauma and
      posttraumatic stress disorder; (b) referral criteria for treatment of abuse
      victims; (c) evidence-based treatments for abused children; (d) reliable, valid,
      and normed measures helpful in assessment; and (e) training needs. Directors
      accurately identified posttraumatic stress disorder symptoms, but additional
      symptoms were misidentified. Directors identified best practices for assessment
      and treatment, but they misidentified non-evidence-based practices. Primary
      reasons for referral for services included severity of abuse and emotional
      response of the child. However, referrals based on assessment findings were not a
      high priority. Directors expressed some training needs for staff consistent with
      issues identified in the study. 

PMID- 25942287
TI  - Mediators of sexual revictimization risk in adult sexual assault victims.
AB  - This study examined sexual risk behaviors and sexual refusal assertiveness in
      relationship to child sexual abuse, emotion dysregulation, and adult sexual
      revictimization. Path analyses of 1,094 survivors who had sex in the past year
      were done to examine sexual risk behavior and sexual refusal assertiveness
      mediational pathways by which child sexual abuse severity and emotion
      dysregulation may affect revictimization over one year in adult female sexual
      assault survivors. Exchanging sex for money and sexual refusal assertiveness were
      significantly associated with emotion dysregulation, whereas exchanging sex for
      money, and not sexual refusal assertiveness, was only significantly related to
      child sexual abuse severity. Both exchanging sex for money and sex refusal
      assertiveness mediated the relationship between emotion dysregulation and adult
      sexual revictimization. Exchanging sex for money mediated the child sexual abuse
      severity-revictimization relationship. These findings demonstrate the importance
      of considering both risky and protective sexual behaviors in research and
      prevention programming that address sexual revictimization in women. 

PMID- 25942288
TI  - Prevalence of Childhood Sexual Abuse among Lesbian, Gay, and Bisexual People: A
      Meta-Analysis.
AB  - In order to determine the prevalence of childhood sexual abuse among gay,
      lesbian, and bisexual individuals, we conducted a meta-analysis that compiled the
      results of 65 articles across 9 countries. The results revealed no significant
      difference in the prevalence of child sexual abuse between homosexual and
      bisexual people for both sexes. The prevalence of child sexual abuse among female
      sexual minorities was significantly higher than that among male sexual
      minorities. The lowest prevalence was found in South America, followed by Asia.
      The definition of child sexual abuse, dimension used to measure sexual
      orientation, year of data collection, and the mean age of participants at the
      time of assessment influenced the estimated prevalence of child sexual abuse. We
      conclude that many variables influence the reported prevalence of child sexual
      abuse among sexual minorities. 

PMID- 25942290
TI  - In vitro meat: A future animal-free harvest.
AB  - In vitro meat production is a novel idea of producing meat without involving
      animals with the help of tissue engineering techniques. This biofabrication of
      complex living products by using various bioengineering techniques is a potential
      solution to reduce the ill effects of current meat production systems and can
      dramatically transform traditional animal-based agriculture by inventing "animal
      free" meat and meat products. Nutrition-related diseases, food-borne illnesses,
      resource use and pollution, and use of farm animals are some serious consequences
      associated with conventional meat production methods. This new way of animal-free
      meat production may offer health and environmental advantages by reducing
      environmental pollution and resource use associated with current meat production
      systems and will also ensure sustainable production of designer, chemically safe,
      and disease-free meat as the conditions in an in vitro meat production system are
      controllable and manipulatable. Theoretically, this system is believed to be
      efficient enough to supply the global demand for meat; however, establishment of
      a sustainable in vitro meat production would face considerably greater technical
      challenges and a great deal of research is still needed to establish this animal
      free meat culturing system on an industrial scale.

PMID- 25942289
TI  - Opioid addiction and withdrawal differentially drive long-term depression of
      inhibitory synaptic transmission in the hippocampus.
AB  - Addictive behavior is increasingly accepted as a drug-associated pathological
      memory in which the hippocampus is profoundly engaged. It has been well
      documented that adaptations of synaptic plasticity of excitatory transmission in
      the hippocampus may contribute to opioid addiction. However, it remains unknown
      whether and how adaptive changes of synaptic plasticity of inhibitory
      transmission in the hippocampus occurs during opioid abuse. Here, we reported
      that a single in vivo morphine exposure (SM) did not affect inhibitory long-term
      depression (I-LTD) in the hippocampus, compared with saline control; while
      repeated morphine exposure (RM) abolished this I-LTD. Interestingly, opioid
      withdrawal for 3-5 days after repeated (RMW), but not a single morphine exposure
      (SMW), largely enhanced I-LTD. More importantly, the I-LTD in single morphine
      treatment is dependent on presynaptic mechanism since it can be blocked by AM251,
      a selective cannabinoid receptor 1 antagonist. While the large I-LTD in RMW group
      is dependent on combinatorial presynaptic and postsynaptic mechanisms since it
      can be blocked by co-application of AM251 and L-type calcium channel blocker
      LaCl3. Thus, these results demonstrate that opioid use and withdrawal drive the
      dynamics of presynaptic and postsynaptic I-LTD expression in the hippocampus that
      may contribute to the persistent behavioral changes during opioid abuse. 

PMID- 25942291
TI  - Complete bilayer adsorption of C16TAB on the surface of mica using neutron
      reflection.
AB  - We present neutron reflection data from an alkylammonium surfactant (C16TAB) at
      the mica/water interface. The system is studied in situ in a noninvasive manner
      and indicates the formation of a complete adsorbed bilayer with little evidence
      of defects. A detailed analysis suggests that the data are not consistent with
      some other previously reported adsorbed structures, such as micelles or
      cylinders. 

PMID- 25942293
TI  - Images of the Month: Tension Colothorax Following Esophageal Dilation.

PMID- 25942294
TI  - Images of the Month: Eosinophilic Colitis of a Nearly Full Colon.

PMID- 25942295
TI  - Images of the Month: Abdominal Leiomyoma: An Unusual Localization in a Male
      Patient.

PMID- 25942296
TI  - Images of the Month: Colonic Schistosomiasis.

PMID- 25942297
TI  - Video of the Month: Emergency Endoscopic Fenestration for Treatment of a
      Recurrence Pancreatic Pseudocyst.

PMID- 25942302
TI  - Usefulness of Measuring microRNAs in Bile and Plasma for Pancreatic Ductal
      Adenocarcinoma Diagnosis.

PMID- 25942303
TI  - Response to Le Large et al.

PMID- 25942304
TI  - Combination therapy with sorafenib and radiofrequency ablation for hepatocellular
      carcinoma: a glimmer of light after the storm trial?

PMID- 25942305
TI  - Response to Facciorusso et al.

PMID- 25942306
TI  - Pancreatic cancer in patients with recently diagnosed chronic pancreatitis.

PMID- 25942307
TI  - Response to Li et al.

PMID- 25942308
TI  - Diverticular disease of the colon and irritable bowel syndrome: it is time to
      differentiate.

PMID- 25942309
TI  - Fecal Microbiota Transplant for Clostridium difficile Colitis-Induced Toxic
      Megacolon.

PMID- 25942310
TI  - Kinetics of Antibodies Against Adalimumab Are Not Associated With Poor Outcomes
      in IBD.

PMID- 25942312
TI  - Bulbar microcircuit model predicts connectivity and roles of interneurons in odor
      coding.
AB  - Stimulus encoding by primary sensory brain areas provides a data-rich context for
      understanding their circuit mechanisms. The vertebrate olfactory bulb is an input
      area having unusual two-layer dendro-dendritic connections whose roles in odor
      coding are unclear. To clarify these roles, we built a detailed compartmental
      model of the rat olfactory bulb that synthesizes a much wider range of
      experimental observations on bulbar physiology and response dynamics than has
      hitherto been modeled. We predict that superficial-layer inhibitory interneurons
      (periglomerular cells) linearize the input-output transformation of the principal
      neurons (mitral cells), unlike previous models of contrast enhancement. The
      linearization is required to replicate observed linear summation of mitral odor
      responses. Further, in our model, action-potentials back-propagate along lateral
      dendrites of mitral cells and activate deep-layer inhibitory interneurons
      (granule cells). Using this, we propose sparse, long-range inhibition between
      mitral cells, mediated by granule cells, to explain how the respiratory phases of
      odor responses of sister mitral cells can be sometimes decorrelated as observed,
      despite receiving similar receptor input. We also rule out some alternative
      mechanisms. In our mechanism, we predict that a few distant mitral cells
      receiving input from different receptors, inhibit sister mitral cells
      differentially, by activating disjoint subsets of granule cells. This
      differential inhibition is strong enough to decorrelate their firing rate phases,
      and not merely modulate their spike timing. Thus our well-constrained model
      suggests novel computational roles for the two most numerous classes of
      interneurons in the bulb. 

PMID- 25942313
TI  - Type 2 diabetic rats on diet supplemented with chromium malate show improved
      glycometabolism, glycometabolism-related enzyme levels and lipid metabolism.
AB  - Our previous study showed that chromium malate improved the regulation of blood
      glucose in mice with alloxan-induced diabetes. The present study was designed to
      evaluate the effect of chromium malate on glycometabolism, glycometabolism
      related enzymes and lipid metabolism in type 2 diabetic rats. Our results showed
      that fasting blood glucose, serum insulin level, insulin resistance index and C
      peptide level in the high dose group had a significant downward trend when
      compared with the model group, chromium picolinate group and chromium trichloride
      group. The hepatic glycogen, glucose-6-phosphate dehydrogenase, glucokinase,
      Glut4, phosphor-AMPKbeta1 and Akt levels in the high dose group were
      significantly higher than those of the model, chromium picolinate and chromium
      trichloride groups. Chromium malate in a high dose group can significantly
      increase high density lipoprotein cholesterol level while decreasing the total
      cholesterol, low density lipoprotein cholesterol and triglyceride levels when
      compared with chromium picolinate and chromium trichloride. The serum chromium
      content in chromium malate and chromium picolinate group is significantly higher
      than that of the chromium trichloride group. The results indicated that the
      curative effects of chromium malate on glycometabolism, glycometabolism-related
      enzymes and lipid metabolism changes are better than those of chromium picolinate
      and chromium trichloride. Chromium malate contributes to glucose uptake and
      transport in order to improved glycometabolism and glycometabolism-related
      enzymes. 

PMID- 25942315
TI  - Role of Preschool and Primary School Children in Epidemics of Influenza A in a
      Local Community in Japan during Two Consecutive Seasons with A(H3N2) as a
      Predominant Subtype.
AB  - Enhanced influenza surveillance was implemented to analyze transmission dynamics
      particularly driving force of influenza transmission in a community during
      2011/12 and 2012/13 seasons in Odate City, Japan. In these two consecutive
      seasons, influenza A(H3N2) was the predominant influenza A subtype. Suspected
      influenza cases were tested by commercial rapid test kits. Demographic and
      epidemiological information of influenza positive cases were recorded using a
      standardized questionnaire, which included age or age group, date of visit, date
      of fever onset, and the result of rapid test kit. Epidemiological parameters
      including epidemic midpoint (EM) and growth rate (GR) were analyzed. In 2012/13
      season, numbers of influenza A positive cases were significantly lower among
      preschool (212 cases) and primary school (224 cases) children than in 2011/12
      season (461 and 538 cases, respectively). Simultaneously, total influenza A cases
      were also reduced from 2,092 in 2011/12 season to 1,846 in 2012/13 season. The
      EMs in preschool and primary school children were earlier than EMs for adult and
      all age group in both 2011/12 and 2012/13 seasons. The GR in 2012/13 season was
      significantly lower than that in 2011/12 season (0.11 and 0.18, respectively, p =
      0.003). Multiple linear regression analysis by school districts revealed that GRs
      in both seasons were significantly correlated with the incidence of school age
      children. Our findings suggest that preschool and primary school children played
      an important role as a driving force of epidemics in the community in both
      2011/12 and 2012/13 seasons. The reduction of total influenza A cases in 2012/13
      season can be explained by decreased susceptible population in these age groups
      due to immunity acquired by infections in 2011/12 season. Further investigations
      are needed to investigate the effect of pre-existing immunity on influenza
      transmission in the community. 

PMID- 25942314
TI  - Chronic Trichuris muris Infection Decreases Diversity of the Intestinal
      Microbiota and Concomitantly Increases the Abundance of Lactobacilli.
AB  - The intestinal microbiota is vital for shaping the local intestinal environment
      as well as host immunity and metabolism. At the same time, epidemiological and
      experimental evidence suggest an important role for parasitic worm infections in
      maintaining the inflammatory and regulatory balance of the immune system. In line
      with this, the prevalence of persistent worm infections is inversely correlated
      with the incidence of immune-associated diseases, prompting the use of controlled
      parasite infections for therapeutic purposes. Despite this, the impact of
      parasite infection on the intestinal microbiota, as well as potential downstream
      effects on the immune system, remain largely unknown. We have assessed the
      influence of chronic infection with the large-intestinal nematode Trichuris
      muris, a close relative of the human pathogen Trichuris trichiura, on the
      composition of the murine intestinal microbiota by 16S ribosomal-RNA gene-based
      sequencing. Our results demonstrate that persistent T. muris infection
      dramatically affects the large-intestinal microbiota, most notably with a drop in
      the diversity of bacterial communities, as well as a marked increase in the
      relative abundance of the Lactobacillus genus. In parallel, chronic T. muris
      infection resulted in a significant shift in the balance between regulatory and
      inflammatory T cells in the intestinal adaptive immune system, in favour of
      inflammatory cells. Together, these data demonstrate that chronic parasite
      infection strongly influences the intestinal microbiota and the adaptive immune
      system. Our results illustrate the complex interactions between these factors in
      the intestinal tract, and contribute to furthering the understanding of this
      interplay, which is of crucial importance considering that 500 million people
      globally are suffering from these infections and their potential use for
      therapeutic purposes. 

PMID- 25942316
TI  - Comparison of operative and non-operative treatment of acute undisplaced or
      minimally-displaced scaphoid fractures: a meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND: Traditionally, acute undisplaced or minimally-displaced scaphoid
      fractures are treated by casting in short- or long-arm casts. Although reports
      have shown that operative treatment is safe, effective and produces satisfactory
      results, outcomes from current studies comparing these two methods are
      questionable. The aim of this meta-analysis was to evaluate the effects of
      operative versus non-operative treatment for acute undisplaced or minimally
      displaced scaphoid fractures in adults. METHODS: Computerized searches were
      performed without language restrictions and all randomized controlled studies
      providing information on the effects of operative versus non-operative treatment
      on the outcomes of acute undisplaced or minimally-displaced scaphoid fractures
      were included. The weighted and standard mean difference (WMD and SMD) or the
      relative risk (RR) were calculated for continuous or dichotomous data
      respectively. RESULTS: A total of six studies reported in seven publications were
      included, representing data on 340 fractures. Meta-analysis indicated that
      operative treatment resulted in significantly better functional outcomes in the
      short term when compared with non-operative treatment. Consistently, patients who
      accepted surgery had a more rapid return to work. Further, surgery was
      advantageous in preventing delayed union of the fractures, a finding supported by
      the results of analysis of the time to fracture union. A number-needed-to-treat
      analysis revealed that more than 20 patients would have to undergo operative
      treatment to prevent one delayed union. CONCLUSION: Acute undisplaced or
      minimally-displaced scaphoid fractures demonstrate faster recovery with operative
      treatment; however, the current meta-analysis does not provide evidence
      supporting the routine use of operative treatment for all acute undisplaced or
      minimally-displaced scaphoid fractures.

PMID- 25942317
TI  - The impact of various time intervals on the supragingival plaque dynamic core
      microbiome.
AB  - OBJECTIVE: The aim of this study was to examine the influence of various time
      intervals on the composition of the supragingival plaque microbiome, especially
      the dynamic core microbiome, and to find a suitable observation interval for
      further studies on oral microbiota. METHODS AND MATERIALS: Eight qualified
      volunteers whose respective age ranges from 25 to 28 years participated in the
      present study. The supragingival plaque was collected from the buccogingival
      surface of the maxillary first molar at eight time slots with different intervals
      (day 0, 1 day, 3 days, 1 week, 2 weeks, 3 weeks, 1 month, and 3 months).
      Bioinformatic analyses was performed based on 16S rDNA pyrosequencing (454
      sequencing platform) targeting at the hypervariable V4-V5 region, in order to
      assess the diversity and variation of the supragingival plaque microbiome.
      RESULTS: A total of 359,565 qualified reads for 64 samples were generated for
      subsequent analyses, which represents 8,452 operational taxonomic units
      identified at 3% dissimilarity. The dynamic core microbiome detected in the
      current study included five phyla, 12 genera and 13 species. At the genus level,
      the relative abundance of bacterial communities under the "1 day," "1 month," and
      "3 months" intervals was clustered into sub-category. At the species level, the
      number of overlapping species remained stable between the "1 month" and "3
      months" intervals, whereas the number of dynamic core species became stable
      within only 1 week. CONCLUSIONS: This study emphasized the impact of different
      time intervals (days, weeks and months) on the composition, commonality and
      diversity of the supragingival microbiome. The analyses found that for various
      types of studies, the time interval of a month is more suitable for observing the
      general composition of the supragingival microbiome, and that a week is better
      for observing the dynamic core microbiome.

PMID- 25942318
TI  - Monetary reward modulates task-irrelevant perceptual learning for invisible
      stimuli.
AB  - Task Irrelevant Perceptual Learning (TIPL) shows that the brain's discriminative
      capacity can improve also for invisible and unattended visual stimuli. It has
      been hypothesized that this form of "unconscious" neural plasticity is mediated
      by an endogenous reward mechanism triggered by the correct task performance.
      Although this result has challenged the mandatory role of attention in perceptual
      learning, no direct evidence exists of the hypothesized link between target
      recognition, reward and TIPL. Here, we manipulated the reward value associated
      with a target to demonstrate the involvement of reinforcement mechanisms in
      sensory plasticity for invisible inputs. Participants were trained in a central
      task associated with either high or low monetary incentives, provided only at the
      end of the experiment, while subliminal stimuli were presented peripherally. Our
      results showed that high incentive-value targets induced a greater degree of
      perceptual improvement for the subliminal stimuli, supporting the role of
      reinforcement mechanisms in TIPL. 

PMID- 25942319
TI  - The Yellow Gorgonian Eunicella cavolini: Demography and Disturbance Levels across
      the Mediterranean Sea.
AB  - The yellow octocoral Eunicella cavolini is one of the most common gorgonians
      thriving in Mediterranean hard-bottom communities. However, information regarding
      its distribution and ecology in several parts of the Mediterranean is lacking,
      while population trends and conservation status remain largely unknown. We
      investigated 19 populations of E. cavolini over three representative geographic
      regions: the NW Mediterranean, CE Adriatic, and N Aegean. Focusing on the upper
      bathymetric range of the species (<40 m), data were collected on the populations'
      upper depth limit, density, colony height, and extent of injury. A three-level
      hierarchical sampling design was applied to assess the existence of spatial
      patterns, using: a) regions (located thousands of km apart), b) localities within
      regions (tens to hundreds of km apart), and c) sites within localities (hundreds
      of m to a few km apart). In the NW Mediterranean and CE Adriatic, the upper
      distribution limit was at depths <=15 m, whereas in the N Aegean most populations
      were found deeper than 30 m. Population density ranged between 4.46-62 colonies
      per m2, while mean colony height was 15.6+/-8.9 SD cm with a maximum of 62 cm.
      The NW Mediterranean sites were characterized by dense populations dominated by
      small colonies (<20 cm), periodic recruitment, and low proportion of large
      gorgonians (>30 cm). The CE Adriatic displayed intermediate densities, with well
      structured populations, and continuous recruitment. In the N Aegean, most
      populations presented low densities, high proportion of large colonies, but low
      number of small colonies, signifying limited recruitment. Disturbance levels, as
      a function of extent and type of injury, are discussed in relation to past or
      present human-induced threats. This work represents geographically the most wide
      ranging demographic study of a Mediterranean octocoral to date. The quantitative
      information obtained provides a basis for future monitoring at a Mediterranean
      scale. 

PMID- 25942320
TI  - Gas Phase Properties of MX2 and MX4 (X = F, Cl) for M = Group 4, Group 14,
      Cerium, and Thorium.
AB  - Structures, vibrational frequencies, and heats of formation were predicted for
      MX4 and both singlet and triplet states of MX2 (M = group 4, group 14, Ce, and
      Th; X = F and Cl) using the Feller-Peterson-Dixon composite electronic structure
      approach based on coupled cluster CCSD(T) calculations extrapolated to the
      complete basis set limit with additional corrections including spin orbit
      effects. The spin-orbit corrections are not large but need to be included for
      chemical accuracy of +/-1 kcal/mol. The singlet-triplet splittings were
      calculated for the dihalides and all compounds have singlet ground states except
      for the dihalides of Ti, Zr, and Ce which have triplet ground states. The
      calculated heats of formation are in good agreement with the available
      experimental data. Our predictions suggest that the experimental heats of
      formation need to be revised for a number of tetrahalides: TiF4, HfF4, PbF4,
      PbCl4, and ThCl4 as well as a number of dihalides: GeF2, SnF2, PbF2, TiF2, and
      TiCl2. The calculated heats of formation were used to predict various
      thermodynamic properties including average M-F and M-Cl bond dissociation
      energies and the reaction energies for MX2 + X2 -> MX4. Edge inversion barriers
      were predicted. The calculated edge inversion barriers for the tetrafluorides
      show that the barriers for the group 14 tetrafluorides decrease with increasing
      atomic number, the group 4 barriers are ~50 kcal/mol and CeF4 and ThF4 have
      inversion barriers of ~25 kcal/mol. 

PMID- 25942322
TI  - Oxidative inter-/intermolecular alkene diamination of hydroxy styrenes with
      electron-rich amines.
AB  - Doubly intermolecular alkene diamination is achieved with electron-rich, terminal
      alkenes through the use of a hypervalent iodine (PhI(OAc)2) reagent, iodide, and
      electron-rich amines. Mono- and disubstituted amines combine with electron-rich
      alkenes, particularly o-hydroxystyrenes, to achieve the greatest level of
      generality. This operationally straightforward protocol, unreliant on
      conventional metal-based activation, is compatible with a broad range of
      functional groups. 

PMID- 25942324
TI  - High-Performance Flexible Ultraviolet (UV) Phototransistor Using Hybrid Channel
      of Vertical ZnO Nanorods and Graphene.
AB  - A flexible ultraviolet (UV) photodetector based on ZnO nanorods (NRs) as
      nanostructure sensing materials integrated into a graphene (Gr) field-effect
      transistor (FET) platform is investigated with high performance. Based on the
      negative shift of the Dirac point (VDirac) in the transfer characteristics of a
      phototransistor, high-photovoltage responsivity (RV) is calculated with a maximum
      value of 3 * 10(8) V W(-1). The peak response at a wavelength of ~365 nm
      indicated excellent selectivity to UV light. The phototransistor also allowed
      investigation of the photocurrent responsivity (RI) and photoconductive gain (G)
      at various gate voltages, with maximum values of 2.5 * 10(6) A W(-1) and 8.3 *
      10(6), respectively, at a gate bias of 5 V. The UV response under bending
      conditions was virtually unaffected and was unchanged after 10,000 bending cycles
      at a bending radius of 12 mm, subject to a strain of 0.5%. The attributes of high
      stability, selectivity, and sensitivity of this flexible UV photodetector based
      on a ZnO NRs/Gr hybrid FET indicate promising potential for future flexible
      optoelectronic devices.

PMID- 25942323
TI  - Pharmacological characterization of the newly synthesized 5-amino-N-butyl-2-(4
      ethoxyphenoxy)-benzamide hydrochloride (BED) as a potent NCX3 inhibitor that
      worsens anoxic injury in cortical neurons, organotypic hippocampal cultures, and
      ischemic brain.
AB  - The Na(+)/Ca(2+) exchanger (NCX), a 10-transmembrane domain protein mainly
      involved in the regulation of intracellular Ca(2+) homeostasis, plays a crucial
      role in cerebral ischemia. In the present paper, we characterized the effect of
      the newly synthesized compound 5-amino-N-butyl-2-(4-ethoxyphenoxy)-benzamide
      hydrochloride (BED) on the activity of the three NCX isoforms and on the
      evolution of cerebral ischemia. BED inhibited NCX isoform 3 (NCX3) activity (IC50
      = 1.9 nM) recorded with the help of single-cell microflorimetry, (45)Ca(2+)
      radiotracer fluxes, and patch-clamp in whole-cell configuration. Furthermore,
      this drug displayed negligible effect on NCX2, the other isoform expressed within
      the CNS, and it failed to modulate the ubiquitously expressed NCX1 isoform.
      Concerning the molecular site of action, the use of chimera strategy and deletion
      mutagenesis showed that alpha1 and alpha2 repeats of NCX3 represented relevant
      molecular determinants for BED inhibitory action, whereas the intracellular
      regulatory f-loop was not involved. At 10 nM, BED worsened the damage induced by
      oxygen/glucose deprivation (OGD) followed by reoxygenation in cortical neurons
      through a dysregulation of [Ca(2+)]i. Furthermore, at the same concentration, BED
      significantly enhanced cell death in CA3 subregion of hippocampal organotypic
      slices exposed to OGD and aggravated infarct injury after transient middle
      cerebral artery occlusion in mice. These results showed that the newly
      synthesized 5-amino-N-butyl-2-(4-ethoxyphenoxy)-benzamide hydrochloride is one of
      the most potent inhibitor of NCX3 so far identified, representing an useful tool
      to dissect the role played by NCX3 in the control of Ca(2+) homeostasis under
      physiological and pathological conditions. 

PMID- 25942326
TI  - An Unexpected Detrimental Effect on the Incidence of Heel Pressure Ulcers
      After Local 5% DMSO Cream Application: A Randomized, Double-blind Study in
      Patients at Risk for Pressure Ulcers.
AB  - Background. Ischemia-reperfusion injury and reactive oxygen species (ROS) are
      considered to play an important role in the pathogenesis of pressure ulcers (PU).
      Antioxidants may diminish the inflammation and damage of these ROS in pressure
      ulcer formation. Dimethyl sulfoxide (DMSO) is a hydroxyl antioxidant that
      inhibits leukocyte adherence. When used topically, DMSO is a safe and well
      tolerated drug with excellent penetrating properties. In this prospective
      randomized study, the effect of topically applied DMSO on the prevention of PU
      formation is analyzed. METHODS: In a randomized double-blinded study, the effects
      of massage with or without DMSO creams were assessed against controls for 2
      locations (ie, heel and buttocks) in 79 patients prone for development of PU.
      RESULTS: There was no difference in PU incidence between the 3 interventions on
      the buttocks. Surprisingly, the topical 5% DMSO cream group showed an increase in
      superficial pressure ulcers for the heel location. CONCLUSION: This is the first
      study on the possible role of DMSO in the prevention of PU. The results suggest
      an adverse effect on PU incidence in heel, whereas on the buttocks the DMSO cream
      seems to have no effect. Possible explanations for this unexpected detrimental
      effect are discussed.

PMID- 25942325
TI  - Structural and biochemical characterization of novel bacterial alpha
      galactosidases belonging to glycoside hydrolase family 31.
AB  - Glycoside hydrolase family 31 (GH31) proteins have been reportedly identified as
      exo-alpha-glycosidases with activity for alpha-glucosides and alpha-xylosides. We
      focused on a GH31 subfamily, which contains proteins with low sequence identity
      (<24%) to the previously reported GH31 glycosidases and characterized two enzymes
      from Pedobacter heparinus and Pedobacter saltans. The enzymes unexpectedly
      exhibited alpha-galactosidase activity, but were not active on alpha-glucosides
      and alpha-xylosides. The crystal structures of one of the enzymes, PsGal31A, in
      unliganded form and in complexes with D-galactose or L-fucose and the catalytic
      nucleophile mutant in unliganded form and in complex with p-nitrophenyl-alpha-D
      galactopyranoside, were determined at 1.85-2.30 A (1 A=0.1 nm) resolution. The
      overall structure of PsGal31A contains four domains and the catalytic domain
      adopts a (beta/alpha)8-barrel fold that resembles the structures of other GH31
      enzymes. Two catalytic aspartic acid residues are structurally conserved in the
      enzymes, whereas most residues forming the active site differ from those of GH31
      alpha-glucosidases and alpha-xylosidases. PsGal31A forms a dimer via a unique
      loop that is not conserved in other reported GH31 enzymes; this loop is involved
      in its aglycone specificity and in binding L-fucose. Considering potential genes
      for alpha-L-fucosidases and carbohydrate-related proteins within the vicinity of
      Pedobacter Gal31, the identified Gal31 enzymes are likely to function in a novel
      sugar degradation system. This is the first report of alpha-galactosidases which
      belong to GH31 family. 

PMID- 25942327
TI  - Use of single or double local muscle flap transfers for coverage of tibia bone
      exposure.
AB  - Many studies emphasize the efficacy of combined orthopedic and plastic
      management for coverage of tibia bone exposure. However, many general hospitals
      do not have resident plastic surgery services to do free tissue transfers. This
      study, therefore, assesses the feasibility of applying single or double local
      muscle flap transfer to reconstruct soft-tissue defects and enhance orthopedic
      management. From July 2002 to December 2004, 34 patients with the same number of
      soft-tissue defects requiring 42 local muscle flaps were enrolled in the study.
      In this case series, no microvascular surgical intervention was performed and no
      plastic surgeons participated. Medical records were analyzed for clinical
      features, treatment strategies, and clinical outcomes. Comparisons were made
      between the single flap group and double flap group. All patients received
      regular follow-up for a minimum of 12 months. The survival rate of local muscle
      flap transfer was 95.2%. The double flap transfer group had significantly larger
      estimated defect areas than the single flap transfer group (P < 0.001). No
      statistical differences existed in healing time (P = 0.10) and complication rates
      (P = 0.58) between the groups. The authors conclude that local muscle flap
      transfer combined with orthopedic management, which is a far less complicated
      method than microvascular free tissue transfer, is suitable for the clinical
      practice when performed by orthopedic surgeons at regional hospitals that do not
      have plastic surgery support. When necessary, local transplantation of multiple
      muscle flaps is a safe, reliable, and effective treatment method. 

PMID- 25942328
TI  - Topical captopril as a novel agent against hypertrophic scar formation in new
      zealand white rabbit skin  .
AB  - Collagen constitutes the majority of extracellular matrix in tissues such as
      bone, cartilage, and especially the skin. Over production and/or decreased
      degradation of collagen fibers could lead to an abnormal wound healing response
      resulting in hypertrophic scarring or keloid formation. Recently, angiotensin II
      has been shown to be present in several cutaneous cells and that it stimulates
      fibroblast proliferation, collagen synthesis, and suppresses matrix
      metalloproteinase activity. The following study examines the effect of topical
      captopril, an inhibitor of angiotensin II production, against hypertrophic scar
      formation in New Zealand white rabbits.Two dermal wounds were made over the
      ventral surface of the ears of each rabbit (n = 6). In each animal, separate
      wounds were treated once per day with either topical 5% captopril or the vehicle
      alone (70% ethanol and 30% propylene glycol) for 7 consecutive days. Wounds were
      harvested at postoperative day 28, and the scar elevation index (SEI) as well as
      collagen organization was evaluated. SEI was reduced from 3.06 in the vehicle
      treated group to 1.94 in the captopril treated wounds (P < 0.05). However, an
      increase in collagen organization was achieved by captopril, while an 8.50%
      decrease in collagen organization scale was derived by captopril compared to the
      vehicle. Results of this study show, for the first time, the efficacy of topical
      captopril as a new agent for the prevention of hypertrophic scar formation in an
      animal model. Thus, captopril might represent the first angiotensin converting
      enzyme inhibitor with a novel pharmacologic application in dermatology. 

PMID- 25942329
TI  - Chronic wound infection: bacterial colonization in the dermal pericolostomic
      region.
AB  - Background. Little is known about the bacteriology of the pericolostomic skin
      region. Identifying these bacteria is important to reduce the morbidity resulting
      from this procedure both to control local infection and to reduce the risk of
      infection in other surgical sites. OBJECTIVE: The scope of this study was to
      determine the prevalence and type of peristomal skin bacteria in colostomy
      patients. METHODS: Thirty-four patients with a temporary colostomy were included
      in the study. Their mean age was 51.6 years. All patients had been colostomized
      for more than 7 weeks. RESULTS: Tissue samples were obtained from the peristomal
      skin and were cultured. Escherichia coli was present in the peristomal skin of
      81.2% of patients with malignant colorectal disease and in all cases of benign
      colorectal disease. The proportion of patients with Bacteroides fragilis (P =
      0.021) and Klebsiella spp (P = 0.003) was higher. The incidence of Peptococcus
      spp (P = 0.068) was lower in patients who had their colostomy for a longer
      period. The cultures in the 34 patients demonstrated that the most common
      bacteria present were: Escherichia coli (31/34), Bacteroides spp (13/34),
      Peptococcus spp (13/34), Klebsiella spp (11/34), and Enterobacter spp (06/34).
      CONCLUSION: The results of this study show that the dermal layer of the abdominal
      wall in the pericolostomic region is colonized by enteric bacteria.

PMID- 25942330
TI  -  Importance of skin perfusion pressure in treatment of critical limb ischemia .
AB  - The authors studied whether skin perfusion pressure (SPP) measurements can be
      used to accurately predict wound healing in critical limb ischemia (CLI) and to
      select peripheral arterial reconstructive procedures. METHODS: Forty-seven
      patients (33 men and 14 women, age 36-83 years) with 69 ischemic limbs with foot
      ulcers or gangrene were studied retrospectively. Skin perfusion pressure was
      compared to the treatment outcomes (ulcers healed and ulcers that failed to
      heal). As a diagnostic test for CLI, the sensitivity, specificity, and the
      positive and the negative predictive values (PPV, NPV) of SPP measurement were
      calculated; the data was then analyzed by the receiver operation characteristic
      (ROC) curve. RESULTS: According to the ROC curve, the best SPP measurement
      performance was at 35 mmHg. CONCLUSION: Wound healing at the appropriate
      amputation level must be predicted to minimize invasive debridement. Skin
      perfusion pressure measurement is useful for predicting wound healing in the
      presence of CLI. Skin perfusion pressure >= 35 mmHg is requisite for wound
      healing; at SPP <35 mmHg, peripheral arterial reconstruction is necessary before
      debridement.

PMID- 25942331
TI  - Controlling the shell formation in hydrothermally reduced graphene hydrogel.
AB  - Graphene hydrogels/aerogels are emerging three-dimensional graphene macroscopic
      assemblies of potential use in many applications including energy storage,
      pollutant adsorption, and gas sensing. In this Letter, we identify, characterize
      and control the formation of the exterior shell structure of graphene hydrogels
      prepared via hydrothermal reduction of graphene oxide. Unlike the porous bulk of
      the hydrogel, the shell is a compact, highly ordered layer with a higher
      electrical conductivity. Shell formation is dependent upon the surface anchoring
      of graphene oxide at the liquid-air and liquid-container interfaces. By
      purposefully weakening surface anchoring of graphene oxide using mild thermal or
      chemical prereduction method prior to hydrothermal reduction, we have succeeded
      in completely suppressing shell formation in the graphene hydrogel. The resulting
      graphene hydrogel shows a lower volume reduction with a porous bulk structure
      immediately accessible from the surface, in contrast to graphene hydrogels
      prepared under conventional conditions. 

PMID- 25942332
TI  - Spectral dependence of nonlinear optical properties of symmetrical octatetraynes
      with p-substituted phenyl end-groups.
AB  - Organic compounds containing conjugated carbon chains have been extensively
      investigated due to their interesting properties including nonlinear optical
      response. Polyynes are a group of compounds where the conjugation can be modified
      by appropriate selection of end-groups, enabling "control" and improvement of
      nonlinear effects. In this work, we investigate three newly synthesized aryl end
      capped octatetraynes, exhibiting strong nonlinear absorption and nonlinear
      refraction properties, which can be attributed to the presence of aryl end-groups
      with electron-withdrawing functional groups suitable for further extending the
      conjugation. Nonlinear optical measurements were performed using a f-scan
      (modified Z-scan) technique with a femtosecond laser system at various
      wavelengths in the visible and near-infrared range (540-1600 nm), revealing
      strong negative third-order nonlinear refraction (3NR) and two-photon absorption
      (2PA) below 600 nm and a noticeable three-photon absorption (3PA) at longer
      wavelengths. The results of spectroscopic characterization and the
      crystallographic data for the investigated compounds are also presented. 

PMID- 25942333
TI  - Identification of the Full 46 Cytochrome P450 (CYP) Complement and Modulation of
      CYP Expression in Response to Water-Accommodated Fractions of Crude Oil in the
      Cyclopoid Copepod Paracyclopina nana.
AB  - The 46 cytochrome P450 (CYP) gene superfamily was identified in the marine
      copepod Paracyclopina nana after searching an RNA-seq database and comparing it
      with other copepod CYP gene families. To annotate the 46 Pn-CYP genes, a
      phylogenetic analysis of CYP genes was performed using a Bayesian method. Pn-CYP
      genes were separated into five different clans: CYP2, CYP3, CYP20, CYP26, and
      mitochondrial. Among these, the principal Pn-CYP genes involved in detoxification
      were identified by comparing them with those of the copepod Tigriopus japonicus
      and were examined with respect to their responses to exposure to a water
      accommodated fraction (WAF) of crude oil and to the alkylated forms of two
      polycyclic aromatic hydrocarbons (PAHs; phenanthrene and fluorene). The
      expression of two Pn-CYP3027 genes (CYP3027F1 and CYP3027F2) was increased in
      response to WAF exposure and also was upregulated in response to the two
      alkylated PAHs. In particular, Pn-CYP3027F2 showed the most notable increase in
      response to 80% WAF exposure. These two responsive CYP genes (Pn-CYP3027F1 and
      CYP3027F2) were also phylogenetically clustered into the same clade of the WAF-
      and alkylated PAH-specific CYP genes of the copepod T. japonicus, suggesting that
      these CYP genes would be those chiefly involved in detoxification in response to
      WAF exposure in copepods. In this paper, we provide information on the copepod P.
      nana CYP gene superfamily and also speculate on its potential role in the
      detoxification of PAHs in marine copepods. Despite the nonlethality of WAF, Pn
      CYP3027F2 was rapidly and significantly upregulated in response to WAF that may
      serve as a useful biomarker of 40% or higher concentration of WAF exposure. This
      paper will be helpful to better understand the molecular mechanistic events
      underlying the metabolism of environmental toxicants in copepods. 

PMID- 25942334
TI  - Response to Comment on "Sphagnum mosses from 21 ombrotrophic bogs in the
      Athabasca bituminous sands region show no significant atmospheric contamination
      of 'heavy metals'".

PMID- 25942335
TI  - Comparison of Ciliary Body Anatomy between American Caucasians and Ethnic Chinese
      Using Ultrasound Biomicroscopy.
AB  - PURPOSE: To compare the ciliary body morphology between the Caucasians and
      Chinese, and to determine the associated anterior segment parameters. METHODS:
      The study groups were comprised of four age- and gender-matched cohorts: American
      Caucasians, American Chinese, southern and northern mainland Chinese. Ultrasound
      biomicroscopy (UBM) was performed to assess the following measurements of the
      ciliary body: trabecular-ciliary process distance (TCPD), trabecular-ciliary
      process angle (TCA) and ciliary body thickness at 1 mm posterior to the scleral
      spur (CBT1). A-scan ultrasonography was used to measure lens thickness (LT) and
      relative lens position (RLP), defined as (ACD + LT/2)/AL. RESULTS: There were
      109, 111, 115 and 117 subjects enrolled in the American Caucasian, American
      Chinese, and southern and northern mainland Chinese groups, respectively.
      Collectively, the Chinese had smaller TCPD (0.834 +/- 0.234 versus 0.940 +/-
      0.236 mm, p < 0.001) and TCA (75.1 +/- 17.9 versus 85.0 +/- 21.5, p < 0.001) than
      Caucasians. No difference was found between the three Chinese subgroups,
      therefore they were combined as one for the following analyses. After multiple
      linear regression analysis, adjusting for age, gender, spherical equivalent (SE)
      and axial length (AL), TCPD and TCA were positively associated with CBT1 and RLP,
      but negatively correlated with LT in the whole sample. The ethnic Chinese had
      significantly smaller CBT1 (SRC = -0.177, p < 0.001) and RLP (SRC = -0.254, p <
      0.001) than that of Caucasians. CONCLUSIONS: Compared with the Caucasians, the
      Chinese had a thinner ciliary body and a more anteriorly positioned lens, which
      may contribute to more anteriorly positioned ciliary processes in this
      population. These findings might help to explain the higher prevalence of angle
      closure in the Chinese.

PMID- 25942336
TI  - Breast cancer treatment by adipose-derived stem cells: an experimental study.
AB  - Breast cancer is a leading cause of deaths in humans. Mesenchymal stem cells
      (MSC) have been identified to possess powerful therapeutic properties in humans.
      The capability of MSC to migrate toward injured tissue suggests their potential
      in new clinical applications. The aim of this study was to investigate the
      potential role of adipose stem cells (ADSCs) for recovering cellular potential
      and delaying or treating breast cancer in an animals model of human breast
      cancer. Cellular adoptive immunotherapy using adipose derived mesenchymal stem
      cells tailored made for Breast Cancer patients would offer a new effective less
      invasive treatment method. ADSCs injected into the cancer tumor did not affect
      tumor growth and the cancer kept growing. ADSCs injected so that they surrounded
      the tumor decreased growth and the tumor had disappeared after 3 to 8 weeks and
      total recovery was maintained throughout the 6 months of study. The adipose stem
      cells are the "active" and "regenerative" part of fat. ADSCs may appear promising
      for their use as "secretor" of the supernatant substance against breast cancer
      cells.

PMID- 25942337
TI  - Clinical safety in using unmatched allogeneic umbilical cord blood mononuclear
      cells transplantations in non-haematopoietic degenerative conditions.
AB  - AIM: Evaluation of safety in using unmatched human allogeneic umbilical cord
      blood cells for therapeutic use in individuals with non-haematopoietic
      degenerative conditions. BACKGROUND: The historical data and several recent
      immunological arguments suggest the therapeutic use of allogeneic Cord Blood
      Mononuclear Cells (CBMNCs), as these cells do not elicit immune response.
      Customarily, HLA matched cord blood MNCs are used along with prolonged
      immunosuppression in treatment of haematological conditions. Lately, unmatched
      CBMNCs are widely used in case of unavailability of HLA matched cord blood. There
      have been suggestions for using unmatched allogeneic cord blood MNCs for
      degenerative conditions without an immunoconditioning regimen. METHOD: 49
      patients with non-haematopoietic degenerative conditions were treated with HLA
      unmatched allogeneic hUCB MNCs. Intrathecal/I.V injections (1-2 million cells/kg
      body weight) were given. Clinical, biochemical and haematological adverse events
      were evaluated. RESULTS: The haematological and biochemical parameters showed no
      major deviation from the normal. Clinically, no acute adverse effects or GVHD
      were observed with the used dosage. CONCLUSION: This study supports/suggests
      clinical safety in therapeutic medical use of unmatched allogeneic CBMNCs when
      used at low dosage in non-haematopoietic degenerative conditions.

PMID- 25942338
TI  - Influence of culture medium and age of bovine blastocysts in established colonies
      of embryonic stem cells.
AB  - The objective of this study was to evaluate the potential of bovine IVF
      blastocysts at different stages of embryonic development in establishing ESC
      like. Furthermore, blastocysts cultured in medium containing (10%) and (2.5%)
      fetal calf serum (FCS) were compared to determine if the serum concentration
      during in vitro culture alters the blastocyst's potential to establish ESC-like
      culture. It was observed that only ICM's from expanded blastocysts adhered to the
      monolayer (n=160) independent of the concentration of serum used during IVF
      culture. There were no observable differences in potential to establish ESC-like
      in embryos cultured with 2,5% or 10% FCS . The bFGF didn't seems to be required
      for maintenance of bovine ESC-like regardless of culture conditions. Blastocysts
      and colonies in primary culture and after the first passage were positive for
      Oct4, Nanog, SSEA-3 and TRA-1-81. Expanded blastocysts gave rise to ESC-like
      colonies, and the addition of LIF was sufficient to maintain cells
      undifferentiated in culture.

PMID- 25942339
TI  - Method of detecting new cancer stem cell-like enrichment in development front
      assay (DFA).
AB  - Wound healing is an inherent property of injured tissue or a group of cells. The
      healing front is always developed by new cells which are progenitor of
      differentiated parental cells. In cancer tissues we aim to study the healing
      front and observed an enriched population of stem cell like properties in the
      developing front when compared to the other areas of the cell matrix. METHOD: In
      vitro scratch assays with special focus on stem cell expression was used to
      analyze metastatic potential of the tumor cell, epithelial to mesenchymal
      transition and rate of cell migration to get an insight into the genes and the
      proteins getting expressed at the developing front. In this protocol we describe
      a fluorescence dependent method to document stem cell like enrichment at the
      developing front of a given wound in drug treated and untreated control cells
      under the same culture conditions in a time lag manner. We have tried to compare
      the rate of cell migration and the expression levels of stem cell markers between
      the treated and untreated cells. RESULTS: CD44 being a cell surface protein and
      being involved in cell migration and proliferation, higher intensity of CD44 was
      observed at the developing front with increasing time. The rate of cell migration
      differed with different treatments and so did the CD44 expression with expression
      being higher in 0.6mM concentration of bleomycin when compared to 0.4mM. Similar
      expression was observed for ALDH1 stem cell marker. This particular technique can
      not only be used for studying expression of CSC markers (like CD44, ALDH1) but
      also in assaying the expression profile of several proteins involved in cellular
      processes like EMT (Epithelial to Mesenchymal Transition), cell migration,
      tumorigeneisis and rate of proliferation. CONCLUSION: Would healing is an
      integral property of solid tissues and in solid tumors properties of solid tissue
      wound are important characteristics of tumor development. Therefore combining the
      properties of stem cell like enrichment in the development front would be an
      important and fast assay to study migratory and metastatic properties of an
      invitro culture.

PMID- 25942340
TI  - HCT116 colonospheres shows elevated expression of hTERT and beta-catenin protein 
      a short report.
AB  - AIM: Clonospheres formed due to modified culture conditions are often studied for
      their stem cell like behaviour. The main objective of the current study is to
      compare the stem cell markers and link it to hTERT levels by monitoring their
      quantitative gene expression as they are potential targets for new generation
      combination therapeutics. METHOD: In the present study we created stable
      colonospheres of Human colon cancer cell line HCT-116 long term culture
      conditions of Serum deprivation. Clonospheres formed after 15 days were collected
      by gentle and enzymatic dissociation was performed. Single cell suspension was
      obtained by mechanically dissociating the cells through a 22G needle. Single
      cells were replanted at a density 1200 cells/ml in Serum Free Medium in the 6
      well plates for further passage. Passaging of cells was done at an interval of 8
      days. The spheres formed were cyto-spun in special slides for Immunocytochemistry
      (ICC) studies for beta-catenin protein and hTERT. The colonospheres were also
      processed for real time PCR expression studies for the same genes to confirm.
      RESULTS: In this present study, immunofluorescence studies revealed high beta
      catenin expression in the nucleus in colonospheres as compared to that of
      differentiated cancer cell line HCT-116 where the signal was localized mostly in
      the membranous and non-nuclear regions. Also increased TRF2 signal in
      colonospheres indicated higher activity of hTERT gene as TRF2 is the direct
      activator of hTERT to protect the telomere. Quantitative PCR studies showed that
      there was a significant over expression (p<0.05) at the mRNA level of the hTERT,
      TRF2, Rap1 genes along with the beta-catenin over expression. Immunofluorescence
      analysis also revealed higher expression of CSC marker CD44 and ALDH1in
      colonospheres compared to the parental population. CONCLUSION: Clonospheres sub
      population is showing higher degree of hTERT gene expression along with beta
      catenin when compared to the parental HCT-116 cancer cells. We also checked the
      co expression of other telomere maintenance genes mainly TRF 2 and Rap1 which
      also showed similar results. Therefore, we conclude that not only hTERT but
      possibly other Sheltrin proteins are regulated by beta-catenin which is co
      expressed.

PMID- 25942341
TI  - Comparative evaluation of efficacy of stem cells in combination with PLA/PGA
      membrane versus sub-epithelial connective tissue for the treatment of multiple
      gingival recession defects: a clinical study.
AB  - BACKGROUND: Umbilical Mesenchymal Stem Cells possess immunoregulatory capacities
      that have been permissive to allogenic transplantation. Recent animal studies
      have demonstrated histologically that bone marrow- derived mesenchymal stem cells
      (MSCs) may enhance the regeneration of periodontal defects in dogs by
      differentiating MSCs into cementoblasts, osteoblasts and periodontal fibroblasts.
      AIM: To compare the clinical efficacy between stem cells in combination with
      PLA/PGA membrane and subepithelial connective tissue graft (SCTG) in the
      treatment of multiple gingival recession defects. METHODS: Twenty four patients
      aged between 20 to 33 years (mean age 27.41 +/- 1.06 years) with multiple
      gingival recession defects on labial or buccal surface of the teeth in the
      aesthetic zone either in maxilla or mandible were treated. The test group was
      treated using stem cells cultured on bioresorbable PLA/PGA membrane, while
      control group was treated using SCTG. Following parameters were assessed, Plaque
      Index (PI),Gingival Bleeding Point Index (GBI), Relative gingival margin level
      (RGML), Relative attachment level (RAL) and Probing pocket depth (PPD) Results:
      In the test group, mean percent defect coverage was 72.43 +/- 13.55 % and the
      predictability was 41.17% for root coverage i.e 14 of 34 defects, while in the
      control group, mean percent defect coverage was 82.06 +/- 10.99 % and the
      predictability was 50 % for root coverage i.e 15 of 30 defects. CONCLUSION: Stem
      cells in combination with bioresorbable PLA/PGA membrane was effective for root
      coverage resulted in a significant reduction in gingival recession, greater gain
      in CAL and WKG. Stem cells in combination with bioresorbable PLA/PGA membrane
      resulted in significantly higher CAL gain than SCTG.

PMID- 25942342
TI  - Indoor air pollution: impact on health and stem cells.
AB  - Nearly 2 million people annually die prematurely from various illness contributed
      by indoor air pollutants (IAP). Such pollutants affect the lungs leading to
      diseases ranging from bronchial diseases to malignant lung cancer. Stem cells
      (SC) with the property of self-renewal, pluripotency, and capability of homing
      into tumors and metastases, have been reported to be promising in treatment of
      lung cancer. In this review, we have tried to understand the role of components
      of IAP affect the SC. Although very few studies have been conducted in these
      lines, existing reports suggest that IAP causes damage to stem cells and their
      niches thereby reducing successful chances of autologous stem cell
      transplantation and therapy. The mechanism by which components of IAP affects the
      functioning of stem cells thus conferring toxicity remains unexplored. The future
      scope of this review lies in revealing answer to underlying questions of repair
      and modulation of stem cells in therapeutic treatment of lung diseases.

PMID- 25942343
TI  - Sensitive characterization of polyphenolic antioxidants in Polygonatum odoratum
      by selective solid phase extraction and high performance liquid chromatography
      diode array detector-quadrupole time-of-flight tandem mass spectrometry.
AB  - The complexity of natural products always leads to the co-elution of interfering
      compounds with bioactive compounds, which then has a detrimental effect on
      structural elucidation. Here, a new method, based on selective solid phase
      extraction combined with 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) spiking and
      high performance liquid chromatography-diode array detector-quadrupole time-of
      flight tandem mass spectrometry (HPLC-DAD-QTOF-MS/MS), is described for sensitive
      screening, selective extraction and identification of polyphenolic antioxidants
      in Polygonatum odoratum. First, 25 polyphenolic antioxidants (1-25) were screened
      by DPPH spiking with HPLC. Second, polydopamine coated Fe3O4 microspheres
      (Fe3O4@PDA) were prepared to selectively extract target antioxidants with
      extraction efficiency from 55% to 100% when the amount of Fe3O4@PDA, extraction
      time, desorption solvent and time were 10mg, 20 min, acetonitrile, and 5 min.
      Third, 25 antioxidants (10 cinnamides and 15 homoisoflavanones) were identified
      by HPLC-DAD-QTOF-MS/MS. Furthermore, the DPPH scavenging activities of purified
      compounds (IC50, 1.6-32.8 MUg/mL) validated the method. Among the identified
      antioxidants, four of them (12, 13, 18 and 19) were new compounds, four of them
      (2, 4, 8 and 14) were first obtained from family Liliaceae, five of them (1, 3,
      5, 7 and 9) were first reported in genus Polygonatum, while one compound (24) was
      first identified in this species. The results indicated that the proposed method
      was an efficient and sensitive approach to explore polyphenolic antioxidants from
      complex natural products.

PMID- 25942344
TI  - Association between CD24-P226-C/T polymorphism and multiple sclerosis: a meta
      analysis.
AB  - BACKGROUND: Multiple sclerosis (MS) is a progressive inflammatory and
      neurodegenerative disease of the central nervous system (CNS), the etiology of
      which is still uncertain. Several case-control studies investigated the
      association between CD24-P226-C/T polymorphism and MS risk, and these studies
      have shown inconsistent results. OBJECTIVE: To address the association of CD24
      P226-C/T polymorphism with MS risk by meta-analysis. METHODS: A comprehensive
      search was conducted to identify all eligible studies of CD24-P226-C/T
      polymorphism and MS risk up to July 2013. The odds ratios (ORs) of CD24 allele
      distributions in MS were analyzed against controls. RESULTS: In total, seven case
      control studies with 949 cases of MS and 1177 controls were included in this meta
      analysis. The overall results showed a significant association between CD24-P226
      C/T polymorphism and MS susceptibility under homozygote comparison model (OR =
      2.496, 95% CI = 1.813-3.435, p < 0.0005), dominant model (OR = 1.367, 95% CI =
      1.147-1.629, p < 0.0005), recessive model (OR = 2.305, 95% CI = 1.700-3.126, p <
      0.0005) and allelic model (OR = 1.422, 95% CI = 1.244-1.625, p < 0.0005).
      However, no significant association was observed under heterozygous comparison
      model (OR = 1.182, 95% CI = 0.982-1.423, p = 0.078). CONCLUSIONS: This meta
      analysis indicates that CD24 P266-C/T polymorphism is more associated with the
      risk of MS than healthy controls. However, due to the small sample size in most
      of the included studies, additional large-scale and well-designed case-control
      studies were required for the validation of this association.

PMID- 25942345
TI  - Meta-analysis: the relationship between CTLA-4 +49 A/G polymorphism and primary
      biliary cirrhosis and type I autoimmune hepatitis.
AB  - OBJECTIVES: CTLA-4 exon-1 +49A > G (rs231775) polymorphism has been reported to
      influence the risk for primary biliary cirrhosis (PBC) as well as type I
      autoimmune hepatitis (AIH-1) in many studies; however, the results still remain
      controversial and ambiguous. This study aimed to determine more precise
      estimations for the relationship between CTLA-4 +49 A > G polymorphism and the
      risk for PBC and AIH-1 by using a meta-analysis. DESIGN AND METHODS: PubMed,
      EMBASE and MEDLINE were searched. Odds ratios (ORs) with 95% confidence intervals
      (CIs) were calculated to estimate the strength of the association. RESULTS:
      Fifteen studies including 3661 patients with PBC and 4427 controls as well as
      seven studies including 1270 patients with AIH-1 and 1614 controls were
      identified. Our pooled analysis revealed that G allele of CTLA-4 gene +49A/G
      polymorphism may confer an increased risk of PBC in overall (p = 0.001, OR =
      1.29; 95% CI = 1.13-1.47) and Caucasians (p = 0.001, OR = 1.32; 95% CI = 1.21
      1.44). At genotypic level, the codominant, dominant and recessive models showed
      no significant association with PBC. With respect to AIH-1, the AG genotype
      demonstrated a trend for association with increased risk of AIH-1 (p = 0.04, AG
      vs. AA, OR = 1.20; 95% CI = 1.01-1.43). However, the CTLA-4 alleles as well as
      genotypes in dominant and recessive models were not associated with a risk for
      AIH-1 in both Caucasians and Asians. CONCLUSIONS: This meta-analysis concluded
      that the CTLA-4 G allele and the AG genotype were associated with an increased
      risk for PBC and AIH-1, respectively, suggesting the CTLA-4 +49 A/G polymorphism
      as a candidate of susceptibility locus to PBC and AIH-1.

PMID- 25942346
TI  - Significant impact of IL-6 -174G/C but inverse relation with -634 C/G
      polymorphism in patients with non-small cell lung cancer in Kashmiri population.
AB  - To study the possible role of proinflammatory interleukin 6 -174 G>C (rs 1800795)
      and -634 C>G (rs 1800796) polymorphism in the pathogenesis of non-small cell lung
      cancer (NSCLC). A total of 190 NSCLC patients and 200 healthy controls were
      evaluated for polymorphic analysis of -174 G/C and -634 C/G by PCR-RFLP followed
      by DNA sequencing. A significant association was observed in the genotypic and
      allelic distribution of IL-6 -174 G/C in the NSCLC group as compared to control
      group [OR = 2.7 (1.77-4.11), p < 0.0001]. Smokers with the -174C allele were
      found to be significantly associated with NSCLC (p = 0.01), while 634C/G SNP
      showed an inverse relation [OR-0.4, p < 0.0001]. The present investigation
      revealed a significant association of the IL6 -174 G/C gene promoter polymorphism
      with NSCLC, and thus, the IL-6 -174G/C genotype can be considered as one of the
      biological markers in the etiology of NSCLC.

PMID- 25942347
TI  - The polymorphisms K469E and G261R of intercellular adhesion molecule-1 and
      susceptibility to inflammatory bowel disease: a meta-analysis.
AB  - OBJECTIVE: The aim of this study was to explore whether polymorphisms of
      intercellular adhesion molecule-1 (ICAM-1) are associated with susceptibility to
      Crohn's disease (CD) and ulcerative colitis (UC). METHODS: The authors conducted
      a meta-analysis on the associations between the polymorphisms K469E and G241R of
      ICAM-1 and susceptibility to CD and UC. RESULTS: A total of 8 studies with 801
      patients with CD, 672 patients with UC, and 1,828 controls were included in the
      meta-analysis. The meta-analysis revealed no association between CD and the ICAM
      1 469E allele among the subjects (OR = 1.175, 95% CI = 0.901-1.533, p = 0.233).
      However, stratification by ethnicity indicated an association between the ICAM-1
      469E allele and CD in Europeans (OR = 1.425, 95% CI = 1.013-2.002, p = 0.042).
      Meta-analysis using the homozygosity also showed an association with CD in
      Europeans (OR = 2.054, 95% CI = 1.036-4.073, p = 0.039). The meta-analysis
      revealed no association between UC and the ICAM-1 K469E polymorphism. No
      association between CD or UC and the ICAM-1 G241R polymorphism was observed.
      CONCLUSIONS: This meta-analysis demonstrates that the ICAM-1 K469E polymorphism
      may be associated with susceptibility to CD in Europeans, but no association was
      found between ICAM-1 K469E and UC. In contrast, the G241R polymorphism was not
      found to be associated with susceptibility to either CD or UC.

PMID- 25942348
TI  - Combined induction therapy with rabbit antithymocyte globulin and rituximab in
      highly sensitized renal recipients.
AB  - Compared to non-sensitized renal transplant recipients, patients with preformed
      alloantibodies are at greater risk of cellular and humoral rejection and
      premature graft failure. We explored the effects of adding B-cell depleting agent
      (rituximab) to standard rabbit anti-thymocyte globulin (rATG) induction regimen
      for patients with panel reactive antibody levels >50%. Following induction
      therapy, 14 recipients were given two doses of rituximab (375 mg/m(2)) within the
      first month post-transplantation. Their long-term outcomes were compared to a
      historical control group of 23 recipients who received rATG alone. Graft survival
      at 5 years was superior with combination therapy compared to induction therapy
      alone (92.9 versus 48.3%, respectively, p = 0.02). While 30% of the rATG alone
      group experienced cellular rejection and 26% humoral rejection, none of rituximab
      plus rATG renal transplant recipients group had rejection. Thus, addition of
      rituximab to rATG provided superior outcomes to rATG alone. This combination
      induction therapy should be considered for a high-risk population.

PMID- 25942350
TI  - IgG Subclasses and Isotypes of VH4-34 Encoded Antibodies.
AB  - VH4-34 gene encoded autoantibodies are elevated in systemic lupus erythematosus
      (SLE) and in other diseases associated with B-cell
      hyperproliferation/dysfunction. One of the autoantigens recognized by VH4-34
      encoded antibodies are branched/linear poly N-acetyl lactosamine chains. Since
      the anti-carbohydrate response in humans is dominated by the IgG2 subclass, here
      we tested whether VH4-34 encoded IgG showed similar subclass segregation. Serum
      samples from SLE, infectious mononucleosis, nasopharyngeal carcinoma and
      hepatitis-C were analyzed. Levels of VH4-34-encoded IgM and IgA isotypes were
      also tested. VH4-34-IgM and IgA were elevated in all four clinical conditions.
      VH4-34-IgG was detected in the IgG1 and IgG3 subclass but not in the IgG2 and
      IgG4 subclass. Interestingly, VH4-34-IgG3 was also detected in serum samples of
      normal healthy adults. These observations are discussed in context of the VH4-34
      gene regulation. VH4-34 repertoire development is of interest since it is the
      only human VH gene profoundly overrepresented in the naive repertoire but counter
      selected for antibody secretion. VH4-34 B-cell could thus become a unique tool to
      inspect germinal center independent/dependent pathways of subclass and isotype
      specific antibody secretion.

PMID- 25942349
TI  - Antigen-specific killer polylactic-co-glycolic acid (PLGA) microspheres can
      prolong alloskin graft survival in a murine model.
AB  - BACKGROUND: The strategy of specifically depleting antigen-specific T cells can
      potentially be used for the treatment of allograft rejection and autoimmunity
      because it does not suppress the overall immune systems. METHODS: In this study,
      we generated killer polylactic-co-glycolic acid (PLGA) microspheres by covalently
      coupling major histocompatibility complex (MHC) class I antigens and apoptosis
      inducing anti-Fas monoclonal antibody (mAb) onto PLGA microspheres. A modified
      double-emulsion method was used for the preparation of cell-sized PLGA
      microspheres. H-2K(b)/peptide monomers were generated in-house and analyzed
      through flow cytometry. The killer PLGA microspheres were administered
      intravenously into BALB/c mice (H-2K(d)) that had previously been grafted with
      skin squares from C57BL/6 mice (H-2K(b)). Tumor cell challenge and third-party
      mixed lymphocyte culture were used to assess the general immune functions of
      host. RESULTS: The alloskin graft survival was prolonged by 4 days. The killer
      PLGA microspheres could specifically deplete the H-2K(b) alloantigen-reactive
      CD8(+) T cells that infiltrated into the alloskin graft but not CD4(+) T cells,
      without impairment of host overall immune function. CONCLUSIONS: Here, we
      initially report that PLGA microspheres, which have been widely used as medicine
      delivering carriers, were used to prepare antigen-specific killer complexes and
      treat allograft rejection. Our data highlight the therapeutic potential of this
      biocompatible and biodegradable antigen-specific killer effector for the
      treatment of allograft rejection and autoimmune disease.

PMID- 25942351
TI  - Triphala exhibits anti-arthritic effect by ameliorating bone and cartilage
      degradation in adjuvant-induced arthritic rats.
AB  - The present study was aimed to investigate the anti-arthritic effect of triphala
      and its underlying mechanism on adjuvant-induced rat model. For comparison
      purpose, non-steroidal anti-inflammatory drug indomethacin was used. Arthritis
      was induced by intradermal injection of complete Freund's adjuvant (0.1 ml) into
      the right hind paw of the Wistar albino rats. Triphala (100 mg/kg body weight
      [bwt]) was administered intraperitoneally (from 11th to 20th day) after the
      arthritis induction. Arthritis induction increased the levels of reactive oxygen
      species (LPO and NO), elastase, and mRNA expression of pro-inflammatory cytokines
      (TNF-alpha, IL-beta, IL-17, IL-6 and MCP-1), inflammatory marker enzymes (iNOS
      and COX-2), receptor activator of nuclear factor kappa-B ligand (RANKL), and
      transcription factors (NF-kB p65 and AP-1) in the paw tissues of rats. The levels
      of bone collagen were found to decrease with increased urinary constituents
      (hydroxyproline and total glycosaminoglycans) in arthritic rats. In addition, the
      immunohistochemistry analysis revealed increased expression of NF-kBp65 and COX-2
      in the paw tissues of arthritic rats. However, administration of triphala
      significantly inhibited the biochemical and molecular alterations in adjuvant
      induced arthritic rats compared to indomethacin (3 mg/kg bwt) as evidenced by the
      radiological and histopathological analysis. In conclusion, our results suggest
      that triphala administration ameliorate bone and cartilage degradation during
      rheumatoid arthritis.

PMID- 25942353
TI  - The role of antioxidants in the chemistry of oxidative stress: A review.
AB  - This Review Article is focused on the action of the reactive oxygenated species
      in inducing oxidative injury of the lipid membrane components, as well as on the
      ability of antioxidants (of different structures and sources, and following
      different mechanisms of action) in fighting against oxidative stress. Oxidative
      stress is defined as an excessive production of reactive oxygenated species that
      cannot be counteracted by the action of antioxidants, but also as a perturbation
      of cell redox balance. Reactive oxygenated/nitrogenated species are represented
      by superoxide anion radical, hydroxyl, alkoxyl and lipid peroxyl radicals, nitric
      oxide and peroxynitrite. Oxidative stress determines structure modifications and
      function modulation in nucleic acids, lipids and proteins. Oxidative degradation
      of lipids yields malondialdehyde and 4-hydroxynonenal, but also isoprostanes,
      from unsaturated fatty acids. Protein damage may occur with thiol oxidation,
      carbonylation, side-chain oxidation, fragmentation, unfolding and misfolding,
      resulting activity loss. 8-hydroxydeoxyguanosine is an index of DNA damage. The
      involvement of the reactive oxygenated/nitrogenated species in disease occurrence
      is described. The unbalance between the oxidant species and the antioxidant
      defense system may trigger specific factors responsible for oxidative damage in
      the cell: over-expression of oncogene genes, generation of mutagen compounds,
      promotion of atherogenic activity, senile plaque occurrence or inflammation. This
      leads to cancer, neurodegeneration, cardiovascular diseases, diabetes, kidney
      diseases. The concept of antioxidant is defined, along with a discussion of the
      existent classification criteria: enzymatic and non-enzymatic, preventative or
      repair-systems, endogenous and exogenous, primary and secondary, hydrosoluble and
      liposoluble, natural or synthetic. Primary antioxidants are mainly chain
      breakers, able to scavenge radical species by hydrogen donation. Secondary
      antioxidants are singlet oxygen quenchers, peroxide decomposers, metal chelators,
      oxidative enzyme inhibitors or UV radiation absorbers. The specific mechanism of
      action of the most important representatives of each antioxidant class
      (endogenous and exogenous) in preventing or inhibiting particular factors leading
      to oxidative injury in the cell, is then reviewed. Mutual influences, including
      synergistic effects are presented and discussed. Prooxidative influences likely
      to occur, as for instance in the presence of transition metal ions, are also
      reminded. 

PMID- 25942352
TI  - Vacillation, indecision and hesitation in moment-by-moment decoding of monkey
      motor cortex.
AB  - When choosing actions, we can act decisively, vacillate, or suffer momentary
      indecision. Studying how individual decisions unfold requires moment-by-moment
      readouts of brain state. Here we provide such a view from dorsal premotor and
      primary motor cortex. Two monkeys performed a novel decision task while we
      recorded from many neurons simultaneously. We found that a decoder trained using
      'forced choices' (one target viable) was highly reliable when applied to 'free
      choices'. However, during free choices internal events formed three categories.
      Typically, neural activity was consistent with rapid, unwavering choices.
      Sometimes, though, we observed presumed 'changes of mind': the neural state
      initially reflected one choice before changing to reflect the final choice.
      Finally, we observed momentary 'indecision': delay forming any clear motor plan.
      Further, moments of neural indecision accompanied moments of behavioral
      indecision. Together, these results reveal the rich and diverse set of internal
      events long suspected to occur during free choice. 

PMID- 25942354
TI  - Cu (I) catalyzed alkyne-azide 1,3-dipolar cycloaddition (CuAAC): Synthesis of
      17alpha-[1-(substituted phenyl)-1,2,3-triazol-4-yl]-19-nor-testosterone-17beta-yl
      acetates targeting progestational and antipro-liferative activities.
AB  - The progestational potency and selectivity of synthetic steroidal agonists can be
      enhanced by even larger chemical moieties at 17alpha-position of the steroid
      backbones. Hereby a series 5a-c and 6a-c of novel 17alpha-[1-(substituted phenyl)
      1,2,3-triazol-4-yl]-19-nortestosterone-17beta-yl acetates were designed and
      synthesized using click chemistry approach searching progestogenic derivatives
      with potential anticancer activity. Compounds 5a,b and 6a,c have affected to
      different extents the three histopatho-logical parameters considered for
      evaluation of their progestational activity. The compounds 5a,b and 6a,c showed
      modifications in rat uterus at 35.7-34.8 nM levels with privileged endometrial
      thickening effect and least change of uterine weight relative to NEA at 52.9 nM
      level. Up to 40 mg/kg dose compounds 5b and 6c were non-toxic. Molecular docking
      of the ligands in PR showed in the majority of cases a conformational fitting
      into the active site different from that of the reference steroid NEA. Compound
      6b revealed about 46.4% growth inhibition of CNS cancer SNB-75 cell line, 56%
      growth inhibition of renal cancer A498 cell line and 56.7% growth inhibition of
      prostate cancer PC-3 cell line which was mediated by cell cycle arrest.
      Drugability of the screened compounds showed tolerated results after being
      challenged to diverse physicochemical parameters. 

PMID- 25942355
TI  - The Process of Interactional Sensitivity Coding in Health Care: Conceptually and
      Operationally Defining Patient-Centered Communication.
AB  - This study aimed to develop a process for measuring sensitivity in provider
      patient interactions to better understand patient-centered communication. The
      authors developed the Process of Interactional Sensitivity Coding in Healthcare
      (PISCH) by incorporating a multimethod investigation into conversations between
      physicians and their patients with type 2 diabetes. The PISCH was then applied
      and assessed for its reliability across the unitization of interactions, the
      activities that were reflected, and the characteristics of patient-centered
      interactional sensitivity that were observed within each unit. In most cases, the
      PISCH resulted in reliable analysis of the interactions, but a few key areas
      (shared decision making, enabling self-management, and responding to emotion)
      were not reliably assessed. Implications of the test of this coding scheme
      include the expansion of the theoretical notion of interactional sensitivity to
      the health care context, rigorous implementation of a multimethod measurement
      development that relied on qualitative and quantitative assessments, and
      important future questions about the role of communication concepts in future
      interpersonal research. 

PMID- 25942358
TI  - One Size Doesn't Fit All: New Continua of Figure Drawings and Their Relation to
      Ideal Body Image.
AB  - OBJECTIVE: This study introduces a new figure drawing measure, the Presentation
      of Images on a Continuum Scale (PICS), which includes continua of bodies from
      thin to obese and thin to muscular for both men and women. PARTICIPANTS:
      Participants were undergraduate students from a private, Catholic university in
      Connecticut. The data were collected in the spring of 2010. METHODS: Three
      hundred forty-eight undergraduates completed an online survey that assessed
      current versus ideal body image as well as attractiveness of body types. RESULTS:
      Results showed that current versus ideal body selection discrepancies on the PICS
      among women (but not among men) were related to several negative outcomes
      involving increased body concerns, less body satisfaction, and lower self-esteem,
      as well as increased drive for muscularity among men. Study implications are
      described from a social norming perspective.

PMID- 25942357
TI  - Enhancing the Photostability of Arylvinylenebipyridyl Compounds as Fluorescent
      Indicators for Intracellular Zinc(II) Ions.
AB  - Arylvinylenebipyridyl (AVB) ligands are bright, zinc(II)-sensitive
      fluoroionophores. The applicability of AVBs as fluorescent indicators for imaging
      cellular zinc(II), however, is limited by low photostability, partially
      attributable to the photoisomerization of the vinylene functionality. Two
      configurationally immobilized (i.e., "locked") AVB analogues are prepared in this
      work. The zinc(II)-sensitive photophysical properties and zinc(II) affinities of
      both AVBs and their locked analogues are characterized in organic and aqueous
      media. The zinc(II) sensitivity of the emission is attributed to the zinc(II)
      dependent energies of the charge transfer excited states of these compounds. The
      configurationally locked ligands have improved photostability, while maintaining
      the brightness and zinc(II) sensibility of their AVB progenitors. The feasibility
      of the "locked" AVB analogues with improved photostability for imaging
      intracellular Zn(II) of eukaryotic cells using laser confocal fluorescence
      microscopy is demonstrated. 

PMID- 25942360
TI  - Docking study: PPARs interaction with the selected alternative plasticizers to
      di(2-ethylhexyl) phthalate.
AB  - Phthalates, used in medical devices (MDs), have been identified as reproductive
      and developmental toxicants. Their toxicity varies somewhat depending on the
      specific phthalate and is in part linked to the activation of Peroxisome
      Proliferating-Activated Receptors (PPARs). So, the use of MDs containing targeted
      phthalates such as di(2-ethylhexyl) phthalate (DEHP) has been challenged by
      European directive 2007/47/EC. Therefore, MDs manufacturers were forced to
      quickly find replacement plasticizers. However, very little toxicological and
      epidemiological studies are available on human health. So, we proceeded to dock
      these chemicals in order to identify compounds that are likely to interact with
      PPARs binding sites. The results obtained are generally very mixed on the
      harmlessness of these alternatives. Moreover, no data exist on the biological
      effects of their possible metabolites. As DEHP toxicity resulted mainly from its
      major metabolites, generalizing the use of these plasticizers without conducting
      extensive studies on the possible effects on human health of their metabolites
      seems inconceivable. 

PMID- 25942359
TI  - A novel recombinant BCG-expressing pro-apoptotic protein BAX enhances Th1
      protective immune responses in mice.
AB  - One-third of the world's population is infected with Mycobacterium tuberculosis
      (MTB). The protective efficacy of bacille Calmette Guerin (BCG) vaccine against
      tuberculosis (TB) in adults is highly controversial even though the BCG vaccine
      has been available for more than 90 years. Because BCG is effective against
      infantile tuberculosis meningitis and miliary tuberculosis in young children and
      provides cost-effective prevention from tuberculosis for developing countries, it
      would be desirable to modify the existing BCG vaccine to provide more
      comprehensive protection. In our study, we constructed a novel recombinant BCG
      strain expressing pro-apoptotic BAX (rBCG::BAX) and demonstrated that it
      significantly induced the apoptosis of macrophages infected with rBCG::BAX both
      in vitro and in vivo. In addition, it significantly enhanced Ag85B-specific IFN
      gamma enzyme-linked immunospot responses, IFN-gamma secretion, IL-2 secretion and
      the ratio of Ag85B-specific IgG2b/IgG1, and it significantly decreased Ag85B
      specific IL-4. Furthermore, it presumably facilitated antigen presentation by
      inducing a significant up-regulation in the expression of MHC-II and B7.1 (CD80)
      co-stimulatory molecules on macrophages. In conclusion, these results suggest
      that the rBCG::BAX strain elicited predominantly a Th1 protective immune
      responses and might be a potential tuberculosis vaccine candidate for further
      study.

PMID- 25942361
TI  - Studies of C-terminal naphthoquinone dipeptides as 20S proteasome inhibitors.
AB  - The ubiquitin proteasome pathway is crucial in regulating many processes in the
      cell. Modulation of proteasome activities has emerged as a powerful strategy for
      potential therapies against much important pathologies. In particular, specific
      inhibitors may represent a useful tool for the treatment of tumors. Here, we
      report studies of a new series of peptide-based analogues bearing a
      naphthoquinone pharmacophoric unit at the C-terminal position. Some derivatives
      showed inhibition in the uM range of the post-acidic-like and chymotrypsin-like
      active sites of the proteasome. 

PMID- 25942362
TI  - Searching for novel scaffold of triazole non-nucleoside inhibitors of HIV-1
      reverse transcriptase.
AB  - Azoles are a promising class of the new generation of HIV-1 non-nucleoside
      reverse transcriptase inhibitors (NNRTIs). From thousands of reported compounds,
      many possess the same basic structure of an aryl substituted azole ring linked by
      a thioglycolamide chain with another aromatic ring. In order to find novel
      extensions for this basic scaffold, we explored the 5-position substitution
      pattern of triazole NNRTIs using molecular docking followed by the synthesis of
      selected compounds. We found that heterocyclic substituents in the 5-position of
      the triazole ring are detrimental to the inhibitory activity of compounds with
      four-membered thioglycolamide linker and this substitution seems to be viable
      only for compounds with shorter two-membered linker. Promising compound, N-(4
      carboxy-2-chlorophenyl)-2-((4-benzyl-5-methyl-4H-1,2,4-triazol-3
      yl)sulfanyl)acetamide, with potent inhibitory activity and acceptable aqueous
      solubility has been identified in this study that could serve as lead scaffold
      for the development of novel water-soluble salts of triazole NNRTIs. 

PMID- 25942363
TI  - Synthesis and evaluation of antioxidant activity of new quinoline-2-carbaldehyde
      hydrazone derivatives: bioisosteric melatonin analogues.
AB  - Overproduction of reactive oxygen species results in oxidative stress that can
      cause fatal damage to vital cell structures. It is known that the use of
      antioxidants could be beneficial in the prevention or delay of numerous diseases
      associated with oxidative stress. Melatonin (MLT) is known as a powerful free
      radical scavenger and antioxidant. It was found that indole ring of MLT can be
      employed by bioisosteric replacement by other aromatic rings. Quinoline
      derivatives constitute an important class of compounds for new drug development.
      Owing to quinoline and hydrazones appealing physiological properties and are
      mostly found in numerous biologically active compounds a series of quinoline-2
      carbaldehyde hydrazone derivatives were synthesized as bioisosteric analogues of
      MLT, characterized and in vitro antioxidant activity was investigated by
      evaluating their reducing effect against oxidation of a redox-sensitive
      fluorescent probe. Cytotoxicity potential of all compounds was investigated both
      by lactate dehydrogenase leakage assay and by MTT assay. 

PMID- 25942364
TI  - Honey as an apitherapic product: its inhibitory effect on urease and xanthine
      oxidase.
AB  - The aim of this study was to evaluate new natural inhibitor sources for the
      enzymes urease and xanthine oxidase (XO). Chestnut, oak and polyfloral honey
      extracts were used to determine inhibition effects of both enzymes. In addition
      to investigate inhibition, the antioxidant capacities of these honeys were
      determined using total phenolic content (TPC), ferric reducing antioxidant power
      (FRAP), and DPPH radical scavenging activity assays. Due to their high phenolic
      content, chestnut and oak honeys are found to be a powerful source for inhibition
      of both enzymes. Especially, oak honeys were efficient for urease inhibition with
      0.012-0.021 g/mL IC50 values, and also chestnut honeys were powerful for XO
      inhibition with 0.028-0.039 g/mL IC50 values. Regular daily consumption of these
      honeys can prevent gastric ulcers deriving from Helicobacter pylori and
      pathological disorders mediated by reactive oxygen species.

PMID- 25942365
TI  - A Membrane-Free Ferrocene-Based High-Rate Semiliquid Battery.
AB  - We report here a ferrocene-based membrane-free, high-rate semiliquid battery that
      takes advantage of a highly soluble ferrocene/ferrocenium redox couple in
      nonaqueous phase. The designed battery exhibits stable capacity retention up to
      94% of theoretical capacity of ferrocene (145 mAh g(-1)) at a broad current rate
      up to 60 C owing to rapid mass transport in a liquid phase and fast redox
      kinetics. The diffusion coefficient and the standard reaction constant are
      determined to be in the order of 10(-6) cm(2) s(-1) and 10(-1) cm s(-1),
      respectively, orders of magnitude greater than those in a solid-phase electrode
      and those in conventional redox flow batteries. Additionally, the battery
      demonstrates power density and energy density exceeding 1400 W L(-1) and 40 Wh L(
      1), respectively, and stable cyclability with capacity retention of ~80% for 500
      cycles. Compared with state-of-the-art energy storage technologies such as Li-ion
      batteries or conventional redox flow batteries, the proposed liquid battery shows
      the potential to be an efficient energy storage system with exceptionally high
      power and reasonable energy density. 

PMID- 25942366
TI  - Positive pressure--analysing the effect of the addition of non-invasive
      ventilation (NIV) to home airway clearance techniques (ACT) in adult cystic
      fibrosis (CF) patients.
AB  - BACKGROUND: There is no published literature on the frequency of use of non
      invasive ventilation (NIV) with airway clearance techniques (ACT) throughout the
      cystic fibrosis (CF) population; 3.9% (191 people of 5062 registered) of the
      United Kingdom CF population older than 16 years are reported to use NIV in
      registry data; however, it is not specified if this is for ACT or respiratory
      failure. Using NIV with ACT decreases work of breathing and fatigue during in
      patient admissions for CF patients. We hypothesised these effects could be
      replicated at home, potentially reducing hospital admissions. METHOD: Fourteen
      adult patients with CF scored ease of clearance and breathlessness with ACT
      before and after addition of NIV to normal ACT routine using a visual analog
      scale. Patient views on NIV with ACT were collected via a structured interview.
      Number of home intravenous (IV) antibiotic courses and days in hospital was
      collected for one year pre- and post-NIV provision. RESULTS: Patients reported
      statistically significant improvements in ease of clearance (p = 0.011) and
      reduced breathlessness during ACT using NIV (p = 0.011). Structured interview
      results indicated patient reports of sputum clearance improved. In-patient days
      were lower, while home IV days were higher after NIV was set up, although not
      statistically significant. CONCLUSION: This study is limited by small numbers;
      however, trends towards less hospital admissions and greater patient ease while
      using NIV with ACT warrant further investigation.

PMID- 25942367
TI  - Fixed Bearings versus Rotating Platforms in Total Knee Arthroplasty.
AB  - Rotating platforms were introduced as an alternative to fixed bearings in hopes
      of providing more natural kinematics and improved clinical outcomes. In-vitro
      wear studies showed significantly less wear with rotating platforms as opposed to
      fixed-bearing designs. Kinematic follow-up studies showed significantly improved
      axial rotation with rotating-platform knees. However, these benefits have failed
      to translate into improved clinical outcomes or survivorship. This article
      reviews our institution's experience, as well as the latest clinical research on
      wear, kinematics, clinical outcomes, and survivorship of fixed-bearing and
      rotating-platform knees. 

PMID- 25942369
TI  - NHEJ enzymes LigD and Ku participate in stationary-phase mutagenesis in
      Pseudomonas putida.
AB  - Under growth-restricting conditions bacterial populations can rapidly evolve by a
      process known as stationary-phase mutagenesis. Bacterial nonhomologous end
      joining (NHEJ) system which consists of the DNA-end-binding enzyme Ku and the
      multifunctional DNA ligase LigD has been shown to be important for survival of
      bacteria especially during quiescent states, such as late stationary-phase
      populations or sporulation. In this study we provide genetic evidence that NHEJ
      enzymes participate in stationary-phase mutagenesis in a population of carbon
      starved Pseudomonas putida. Both the absence of LigD or Ku resulted in
      characteristic spectra of stationary-phase mutations that differed from each
      other and also from the wild-type spectrum. This indicates that LigD and Ku may
      participate also in mutagenic pathways that are independent from each other. Our
      results also imply that both phosphoesterase (PE) and polymerase (POL) domains of
      the LigD protein are involved in the occurrence of mutations in starving P.
      putida. The participation of both Ku and LigD in the occurrence of stationary
      phase mutations was further supported by the results of the analysis of mutation
      spectra in stationary-phase sigma factor RpoS-minus background. The spectra of
      mutations identified in the RpoS-minus background were also distinct if LigD or
      Ku was absent. Interestingly, the effects of the presence of these enzymes on the
      frequency of occurrence of certain types of mutations were different or even
      opposite in the RpoS-proficient and deficient backgrounds. These results imply
      that RpoS affects performance of mutagenic pathways in starving P. putida that
      utilize LigD and/or Ku. 

PMID- 25942370
TI  - Improving Properties of a Novel beta-Galactosidase from Lactobacillus plantarum
      by Covalent Immobilization.
AB  - A novel beta-galactosidase from Lactobacillus plantarum (LPG) was over-expressed
      in E. coli and purified via a single chromatographic step by using lowly
      activated IMAC (immobilized metal for affinity chromatography) supports. The pure
      enzyme exhibited a high hydrolytic activity of 491 IU/mL towards o-nitrophenyl
      beta-D-galactopyranoside. This value was conserved in the presence of different
      divalent cations and was quite resistant to the inhibition effects of different
      carbohydrates. The pure multimeric enzyme was stabilized by multipoint and
      multisubunit covalent attachment on glyoxyl-agarose. The glyoxyl-LPG immobilized
      preparation was over 20-fold more stable than the soluble enzyme or the one-point
      CNBr-LPG immobilized preparation at 50  degrees C. This beta-galactosidase was
      successfully used in the hydrolysis of lactose and lactulose and formation of
      different oligosaccharides was detected. High production of galacto
      oligosaccharides (35%) and oligosaccharides derived from lactulose (30%) was
      found and, for the first time, a new oligosaccharide derived from lactulose,
      tentatively identified as 3'-galactosyl lactulose, has been described.

PMID- 25942368
TI  - Role of the yeast DNA repair protein Nej1 in end processing during the repair of
      DNA double strand breaks by non-homologous end joining.
AB  - DNA double strand breaks (DSB)s often require end processing prior to joining
      during their repair by non-homologous end joining (NHEJ). Although the yeast
      proteins, Pol4, a Pol X family DNA polymerase, and Rad27, a nuclease, participate
      in the end processing reactions of NHEJ, the mechanisms underlying the
      recruitment of these factors to DSBs are not known. Here we demonstrate that
      Nej1, a NHEJ factor that interacts with and modulates the activity of the NHEJ
      DNA ligase complex (Dnl4/Lif1), physically and functionally interacts with both
      Pol4 and Rad27. Notably, Nej1 and Dnl4/Lif1, which also interacts with both Pol4
      and Rad27, independently recruit the end processing factors to in vivo DSBs via
      mechanisms that are additive rather than redundant. As was observed with
      Dnl4/Lif1, the activities of both Pol4 and Rad27 were enhanced by the interaction
      with Nej1. Furthermore, Nej1 increased the joining of incompatible DNA ends in
      reconstituted reactions containing Pol4, Rad27 and Dnl4/Lif1, indicating that the
      stimulatory activities of Nej1 and Dnl4/Lif1 are also additive. Together our
      results reveal novel roles for Nej1 in the recruitment of Pol4 and Rad27 to in
      vivo DSBs and the coordination of the end processing and ligation reactions of
      NHEJ. 

PMID- 25942371
TI  - A High-Throughput UHPLC-QqQ-MS Method for Polyphenol Profiling in Rose Wines.
AB  - A rapid, sensitive and selective analysis method using Ultra High Performance
      Liquid Chromatography coupled to triple-quadrupole Mass Spectrometry (UHPLC-QqQ
      MS) has been developed for the quantification of polyphenols in rose wines. The
      compound detection being based on specific MS transitions in Multiple Reaction
      Monitoring (MRM) mode, the present method allows the selective quantification of
      up to 152 phenolic and two additional non-phenolic wine compounds in 30 min
      without sample purification or pre-concentration, even at low concentration
      levels. This method was repeatably applied to a set of 12 rose wines and thus
      proved to be suitable for high-throughput and large-scale metabolomics studies. 

PMID- 25942372
TI  - Cytotoxic Lignan from the Non-Transformed Root Culture of Phyllanthus amarus.
AB  - A new lignan from the non-transformed root in vitro cultures of Phyllanthus
      amarus was isolated. The structure of the compound was established on the basis
      of one- and two-dimensional NMR, as well as mass spectrometry data, as 7'
      oxocubebin dimethylether (1,4-bis(benzo[d][1,3]dioxol-5-yl)-2,3
      bis(methoxymethyl)butan-1-on). The non-transformed root cultures of P. amarus
      showed to be a selective source of this compound. The lignan revealed strong
      cytotoxic activity against HeLa cell line with an IC50 value of 3.8 ug/mL. 

PMID- 25942373
TI  - Antinociceptive Activity and Toxicity Evaluation of the Fatty Oil from Plukenetia
      polyadenia Mull. Arg. (Euphorbiaceae).
AB  - Seed oil (Pp-oil) of Plukenetia polyadenia is used by native people of the
      Brazilian Amazon against arthritis and rheumatism, spreading it on the arms and
      legs to reduce the pain and inflammation. Pp-oil was obtained by pressing dried
      seeds at room temperature to give a 47.0% yield of oil. It was then subjected to
      fatty acid composition analysis. The principal fatty acids were linoleic acid
      (46.5%), alpha-linolenic acid (34.4%) and oleic acid (13.9%). Then, it was
      evaluated for its antinociceptive activity in mice, using the acetic acid-induced
      abdominal writhing, hot plate and formalin test models. Additionally, its
      toxicity was determined. The Pp-oil proved to have no toxicological effects,
      showing dose-dependent antinociceptive effect under chemical stimulation. At oral
      doses of 25-100 mg/kg, Pp-oil significantly reduced the abdominal writhes in the
      writhing test. A higher oral dose of 200 mg/kg did not induce alterations in the
      latency time of the hot plate test when compared to the control, suggesting an
      analgesic activity of peripheral origin. At oral doses of 50 and 100 mg/kg, the
      Pp-oil significantly reduced the second phase of the algic stimulus in the
      formalin test. In addition, the antinociception of Pp-oil was reversed by
      naloxone in the evaluation of its mechanism of action. Therefore, the Pp-oil
      proved to be safe at very high doses and to show significant analgesic
      properties. The role of Pp-oil is still being investigated with respect the
      mechanism of action, but the results suggest that opiod receptors could be
      involved in the antinociception action observed for the oil of P. polyadenia. 

PMID- 25942374
TI  - Effect of Culture Conditions on Metabolite Production of Xylaria sp.
AB  - Seeking a strategy for triggering the cryptic natural product biosynthesis to
      yield novel compounds in the plant-associated fungus Xylaria sp., the effect of
      culture conditions on metabolite production was investigated. A shift in the
      production of five known cytochalasin-type analogues 1-5 to six new alpha-pyrone
      derivatives, xylapyrones A-F (compounds 6-11), from a solid to a liquid medium
      was observed. These compounds were identified by analysis of 1D and 2D NMR and
      HRMS data. Compounds 1-3 showed moderate cytotoxicity against HepG2 and Caski
      cancer cell lines with IC50 values ranging from 25 to 63 MUM and compounds 4-11
      were found to be inactive, with IC50 values>100 MUM.

PMID- 25942375
TI  - Development of inhibition of return for eye gaze in adolescents.
AB  - Gaze is an important cue in social interaction. Gaze direction can attract
      attention and produce a cuing effect as well as cause inhibition of return (IOR)-
      a slower response to an item at a previously attended-to location. Because gaze
      cue is sensitive to an individual's social interaction ability and such ability
      matures in adolescents, we examined how social attention by gaze cue varies with
      age. Three typically developing groups-ages 6 to 8, 9 to 12, and 13 to 15 years-
      were recruited. Each age group had 27 participants. Three main findings were
      observed. First, younger participants generated greater cuing effects than older
      ones. Second, reliable gaze-induced IOR was observed only in the 9- to 12-year
      and 13- to 15--year age groups, whereas the 6- to 8-year age group paid attention
      to gaze direction regardless of cue duration. Third, the 13- to 15-year age group
      showed gaze-induced IOR earlier (1200 ms) in the time course than expected (2400
      ms). Our results suggest that the inhibition mechanism develops later than the
      facilitation mechanism in social attention.

PMID- 25942377
TI  - Influence of Food Matrix on Sterol and Stanol Activity.
AB  - The format and matrix in which functional food ingredients are delivered may
      influence their bioactivity in vivo. Therefore, this paper will review studies
      which have examined plant sterols and stanols being consumed in varying formats
      and matrices, i.e., fat-containing foods versus low or non-fat foods, solid foods
      versus liquid foods, capsules or tables versus foods. Furthermore, this paper
      will examine the issue of providing plant sterols and stanols in either free or
      esterified form. Finally, a discussion on the importance of microemulsion
      stability of the sterols and stanols is elaborated. Based on the reviewed
      information, it would seem that plant sterols and stanols are effective in all
      food and capsule/tablet formats, and in both free and esterified form. Some
      failures in clinical trials may be due to unstable microemulsion of sterols. 

PMID- 25942376
TI  - Inhibition of protein phosphatase 2A with the small molecule LB100 overcomes cell
      cycle arrest in osteosarcoma after cisplatin treatment.
AB  - Osteosarcoma is the most common primary malignant bone tumor and affects a
      significant portion of pediatric oncology patients. Although surgery and adjuvant
      chemotherapy confer significant survival benefits, many patients go on to develop
      metastatic disease, particularly to the lungs, secondary to development of drug
      resistance. Inhibition of protein phosphatase 2A with the small molecule, LB100,
      has demonstrated potent chemo- and radio-sensitizing properties in numerous pre
      clinical tumor models. In this study, we showed that LB100 overcame DNA repair
      mechanisms in osteosarcoma cells treated with cisplatin, in vitro, and
      recapitulated these findings in an in vivo xenograft model. Notably, the addition
      of LB100 to cisplatin prevented development of pulmonary metastases in the
      majority of treated animals. Our data indicated the mechanism of chemo
      sensitization by LB100 involved abrogation of the ATM/ATR-activated DNA damage
      response, leading to hyperphosphorylation of Chk proteins and persistent cyclin
      activity. In addition, LB100 exposure suppressed Akt signaling, leading to Mdm2
      mediated proteasomal degradation of functional p53. Taken together, LB100
      prevented repair of cisplatin-induced DNA damage, resulting in mitotic
      catastrophe and cell death.

PMID- 25942378
TI  - Effects of Plant Sterol and Stanol Consumption on Blood Pressure and Endothelial
      Function.
AB  - The cholesterol lowering effects of plant sterols and stanols are a well
      established complementary means by which to reduce blood cholesterol
      concentrations. The average reduction in LDL cholesterol concentrations is
      approximately -10% following a 28-day supplementation protocol. There is very
      little known regarding what, if any, effect plant sterols and stanols have on
      other cardiometabolic risk factors such as blood pressure and endothelial
      function. Here we review the available literature on this topic and attempt to
      draw conclusions regarding any benefit or risk for blood pressure and endothelial
      function linked to plant sterol and stanol supplementation. Generally there has
      been very little work focusing on changes in blood pressure or endothelial
      function following plant sterol or stanol intervention, but these factors have
      been measured in some cases as secondary outcomes. Overall, there is little
      evidence to support either positive or negative effects of plant sterol or stanol
      supplementation of blood pressure and the data surrounding endothelial function
      is quite inconclusive. This area of research would benefit from well controlled
      mechanistic studies in animals and primary interventions in humans which focus on
      ambulatory blood pressure, central blood pressure and endothelial function. 

PMID- 25942379
TI  - Influence of physical fitness on antioxidant activity and malondialdehyde level
      in healthy older adults.
AB  - The aim of this study was to investigate how physical fitness level could affect
      antioxidant activity and malondialdehyde (MDA) level at rest and in response to
      exhaustive exercise in healthy older adults. Fifty older adults (average age:
      66.1 +/- 3.8 years) were divided according to their physical fitness level into
      an unfit group (UG) (n = 15), a low fitness level group (LFG) (n = 18), and a
      high fitness level group (HFG) (n = 17). Fitness status was classified based on
      answers to a questionnaire about physical activity in the previous 12 months.
      Before and after an incremental cycle ergometer test to exhaustion, the following
      markers were assessed: superoxide dismutase (SOD), glutathione peroxidase (GPX),
      glutathione reductase, ascorbic acid, alpha-tocopherol, and MDA. At rest, SOD,
      GPX, and alpha-tocopherol activities were higher in the HFG (p < 0.05), whereas
      MDA level was lower in the LFG in comparison with the 2 other groups (p < 0.05).
      During the postexercise period, antioxidant activity increased only in the LFG
      and the HFG (GPX, SOD, and alpha-tocopherol). MDA level increased in all groups
      after the exercise (p < 0.05). In addition, MDA level was higher during the
      recovery period in the HFG as compared with the others groups. This study
      concluded that both low and high physical fitness levels help maintain better
      antioxidant defenses in older adults. However, a higher physical fitness level,
      rather than a lower physical fitness level, could increase lipid peroxidation. 

PMID- 25942380
TI  - A year-long quality improvement project on fluid management using blood volume
      monitoring during hemodialysis.
AB  - BACKGROUND: Inadequate removal of extracellular volume markedly increases blood
      pressure and contributes to high morbidity and mortality in hemodialysis
      patients. Advances in fluid management are needed to improve clinical outcomes.
      The aim of this quality improvement project was to examine the advantages of
      using a hematocrit-based, blood volume monitor (Crit-Line * ) for 12 months, as
      part of a clinic-wide, fluid management program in one dialysis facility.
      METHODS: Forty-five individuals were receiving hemodialysis at one facility at
      project initiation and are included in this analysis. Monthly averaged clinical
      parameters (dialysis treatment information, blood pressures, blood volume, and
      laboratory data) were compared from Months 1-12. Analyses were conducted overall
      and according to the presence/absence of hypertension at Month 1 (Baseline).
      Antihypertensive medication changes were assessed for patients with hypertension
      at Month 1. RESULTS: Average hemodialysis treatment time (+10.6 minutes, p =
      0.002), eKt/V (+0.25, p < 0.001) and online clearance (+0.21, p < 0.0001)
      increased significantly in Month 12 versus Month 1. Average albumin levels and
      normalized protein catabolic rate increased from Month 1 to 12. Post-dialysis
      systolic blood pressure (SBP) decreased by Month 12 (p = 0.003). In hypertensive
      patients (SBP >= 140 mmHg in Month 1), there were significant differences in pre-
      and post-dialysis SBP between Month 1 and Month 12 (pre-hemodialysis: p = 0.02;
      post-hemodialysis: p = 0.0003), and antihypertensive medication use decreased in
      29% of patients, while only 11% increased use. Treatment time in hypertensive
      patients increased by 15.4 minutes (p = 0.0005). LIMITATIONS: This was a single,
      clinic-wide, quality improvement project with no control group. All data analyzed
      were from existing clinical records, so only routinely measured clinical
      variables were available and missing data were possible. CONCLUSIONS: During this
      year-long fluid management quality improvement project, decreases in post
      dialysis SBP and increases in adequacy and treatment time were observed. Patients
      with hypertension at Month 1 experienced reductions in pre-dialysis SBP and
      antihypertensive medications.

PMID- 25942381
TI  - Marsdenia tenacssima extract and its functional components inhibits proliferation
      and induces apoptosis of human Burkitt leukemia/lymphoma cells in vitro and in
      vivo.
AB  - Burkitt lymphoma is a fast growing non-Hodgkin lymphoma that occurs primarily in
      young males. The causes of Burkitt lymphoma include chromosome rearrangement and
      virus infection, but accurate and complete reasons remain to be discovered. The
      available treatment for Burkitt lymphoma is chemotherapy and radiation therapy.
      It is a highly aggressive B-cell neoplasm with not all patients cured, in spite
      of current therapies. This study evaluated the effects of traditional Chinese
      medicine Marsdenia tenacssima (MTE) and its component compound Tenacigenoside A
      (TGTA) and 11alpha-O-benzoyl-12beta-O-acetyltenacigenin B (TGTB) on human Burkitt
      lymphoma growth. It was observed that MTE, TGTA or TGTB inhibited cell growth and
      induced apoptosis of Burkitt lymphoma cells in culture. In lymphoma bearing
      NOD/SCID nude mice, both TGTA and TGTB inhibited tumor growth and improved animal
      survival. TGTA and TGTB significantly increased tumor cell apoptosis on lymphoma
      bearing mice, primarily through down-regulation of BCL2 and BCL-XL and up
      regulation of BID.

PMID- 25942382
TI  - Safe and effective use of ponatinib in a patient with chronic myeloid leukemia
      and acute venous thromboembolism on therapeutic anti-coagulation.

PMID- 25942383
TI  - Synergism between arsenic trioxide and aclacinomycin in acute myeloid leukemia.

PMID- 25942384
TI  - Corneal sub-basal neural damage pattern in multiple myeloma patients treated with
      bortezomib: an in vivo confocal study.

PMID- 25942385
TI  - Alteration of the rat cecal microbiome during colonization with the helminth
      Hymenolepis diminuta.
AB  - The microbiome is now widely recognized as being important in health and disease,
      and makes up a substantial subset of the biome within the ecosystem of the
      vertebrate body. At the same time, multicellular, eukaryotic organisms such as
      helminths are being recognized as an important component of the biome that shaped
      the evolution of our genes. The absence of these macroscopic organisms during the
      early development and life of humans in Western culture probably leads to a wide
      range of human immunological diseases. However, the interaction between the
      microbiome and macroscopic components of the biome remains poorly characterized.
      In this study, the microbiome of the cecum in rats colonized for 2 generations
      with the small intestinal helminth Hymenolepis diminuta was evaluated. The
      introduction of this benign helminth, which is of considerable therapeutic
      interest, led to several changes in the cecal microbiome. Most of the changes
      were within the Firmicutes phylum, involved about 20% of the total bacteria, and
      generally entailed a shift from Bacilli to Clostridia species in the presence of
      the helminth. The results point toward ecological relationships between various
      components of the biome, with the observed shifts in the microbiome suggesting
      potential mechanisms by which this helminth might exert therapeutic effects. 

PMID- 25942386
TI  - A Comparison of Accelerometer Accuracy in Older Adults.
AB  - Older adults' gait disorders present challenges for accurate activity monitoring.
      The current study compared the accuracy of accelerometer-detected to hand-tallied
      steps in 50 residential care/assisted living residents. Participants completed
      two walking trials wearing a Fitbit(r) Tracker and waist-, wrist-, and ankle
      mounted Actigraph GT1M. Agreement between accelerometer and observed counts was
      calculated using concordance correlation coefficients (CCC), accelerometer to
      observed count ratios, accelerometer and observed count differences, and Bland
      Altman plots. Classification and Regression Tree analysis identified minimum gait
      speed thresholds to achieve accelerometer accuracy >=0.80. Participants' mean age
      was 84.2 and gait speed was 0.64 m/s. All accelerometers underestimated true
      steps. Only the ankle-mounted GT1M demonstrated positive agreement with observed
      counts (CCC = 0.205). Thresholds for 0.80 accuracy were gait speeds >=0.56 m/s
      for the Fitbit and gait speeds >=0.71 m/s for the ankle-mounted GT1M. Gait speed
      and accelerometer placement affected activity monitor accuracy in older adults.

PMID- 25942388
TI  - Age- and education-adjusted normative data for the Montreal Cognitive Assessment
      (MoCA) in older adults age 70-99.
AB  - The original validation study for the Montreal Cognitive Assessment (MoCA)
      suggests a cutoff score of 26; however, this may be too stringent for older
      adults, particularly for those with less education. Given the rapidly increasing
      number of older adults and associated risk of dementia, this study aims to
      provide appropriate age- and education-adjusted norms for the MoCA. Data from 205
      participants in an ongoing longevity study were used to derive normative data.
      Individuals were grouped based on age (70-79, 80-89, 90-99) and education level
      (<=12 Years, 13-15, >=16 Years). There were significant differences between age
      and education groups with younger and more educated participants outperforming
      their counterparts. Forty-six percent of our sample scored below the suggested
      cutoff of 26. These normative data may provide a more accurate representation of
      MoCA performance in older adults for specific age and education stratifications.

PMID- 25942389
TI  - Icosandrin, a novel peltogynoid from the fruits of Phytolacca icosandra
      (Phytolaccaceae).
AB  - Besides the known compounds ( +/- ) 3,3-bis-demethylpinoresinol (2), americanol A
      (3), spergulagenic acid (4), epi-acetylaleuritolic acid (5), 6'-palmityl-alpha
      spinateryl-d-glucoside (6a) and 6'-palmityl-delta(7)-stigmastenyl-d-glucoside
      (6b), a novel peltogynoid (1) named icosandrin was obtained from the dried fruits
      of Phytolacca icosandra. This new compound was characterised by 1D-/2D-NMR, UV,
      IR and HR-MS techniques as 11xi-methoxy-6,7-methylenedioxy-[2]benzopyrano-[4,3
      b][1]-benzopyran-4-one. Toxicity of 1 was assessed through the Brine Shrimp
      Lethality Assay. Lignan 2 is reported for the first time in Phytolaccaceae
      family. 

PMID- 25942390
TI  - Phytoscreening with SPME: Variability Analysis.
AB  - Phytoscreening has been demonstrated at a variety of sites over the past 15 years
      as a low-impact, sustainable tool in delineation of shallow groundwater
      contaminated with chlorinated solvents. Collection of tree cores is rapid and
      straightforward, but low concentrations in tree tissues requires sensitive
      analytics. Solid-phase microextraction (SPME) is amenable to the complex matrix
      while allowing for solvent-less extraction. Accurate quantification requires the
      absence of competitive sorption, examined here both in laboratory experiments and
      through comprehensive examination of field data. Analysis of approximately 2,000
      trees at numerous field sites also allowed testing of the tree genus and diameter
      effects on measured tree contaminant concentrations. Collectively, while these
      variables were found to significantly affect site-adjusted perchloroethylene
      (PCE) concentrations, the explanatory power of these effects was small (adjusted
      R(2) = 0.031). 90th quantile chemical concentrations in trees were significantly
      reduced by increasing Henry's constant and increasing hydrophobicity. Analysis of
      replicate tree core data showed no correlation between replicate relative
      standard deviation (RSD) and wood type or tree diameter, with an overall median
      RSD of 30%. Collectively, these findings indicate SPME is an appropriate
      technique for sampling and analyzing chlorinated solvents in wood and that
      phytoscreening is robust against changes in tree type and diameter.

PMID- 25942391
TI  - The decomposition of fine and coarse roots: their global patterns and controlling
      factors.
AB  - Fine root decomposition represents a large carbon (C) cost to plants, and serves
      as a potential soil C source, as well as a substantial proportion of net primary
      productivity. Coarse roots differ markedly from fine roots in morphology,
      nutrient concentrations, functions, and decomposition mechanisms. Still poorly
      understood is whether a consistent global pattern exists between the
      decomposition of fine (<2 mm root diameter) and coarse (>=2 mm) roots. A
      comprehensive terrestrial root decomposition dataset, including 530 observations
      from 71 sampling sites, was thus used to compare global patterns of decomposition
      of fine and coarse roots. Fine roots decomposed significantly faster than coarse
      roots in middle latitude areas, but their decomposition in low latitude regions
      was not significantly different from that of coarse roots. Coarse root
      decomposition showed more dependence on climate, especially mean annual
      temperature (MAT), than did fine roots. Initial litter lignin content was the
      most important predictor of fine root decomposition, while lignin to nitrogen
      ratios, MAT, and mean annual precipitation were the most important predictors of
      coarse root decomposition. Our study emphasizes the necessity of separating fine
      roots and coarse roots when predicting the response of belowground C release to
      future climate changes. 

PMID- 25942392
TI  - Bias in ligation-based small RNA sequencing library construction is determined by
      adaptor and RNA structure.
AB  - High-throughput sequencing (HTS) has become a powerful tool for the detection of
      and sequence characterization of microRNAs (miRNA) and other small RNAs (sRNA).
      Unfortunately, the use of HTS data to determine the relative quantity of
      different miRNAs in a sample has been shown to be inconsistent with quantitative
      PCR and Northern Blot results. Several recent studies have concluded that the
      major contributor to this inconsistency is bias introduced during the
      construction of sRNA libraries for HTS and that the bias is primarily derived
      from the adaptor ligation steps, specifically where single stranded adaptors are
      sequentially ligated to the 3' and 5'-end of sRNAs using T4 RNA ligases. In this
      study we investigated the effects of ligation bias by using a pool of randomized
      ligation substrates, defined mixtures of miRNA sequences and several combinations
      of adaptors in HTS library construction. We show that like the 3' adaptor
      ligation step, the 5' adaptor ligation is also biased, not because of primary
      sequence, but instead due to secondary structures of the two ligation substrates.
      We find that multiple secondary structural factors influence final representation
      in HTS results. Our results provide insight about the nature of ligation bias and
      allowed us to design adaptors that reduce ligation bias and produce HTS results
      that more accurately reflect the actual concentrations of miRNAs in the defined
      starting material. 

PMID- 25942393
TI  - Persistence of the recombinant genomes of woodchuck hepatitis virus in the mouse
      model.
AB  - Hydrodynamic injection (HI) with a replication competent hepatitis B virus (HBV)
      genome may lead to transient or prolonged HBV replication in mice. However, the
      prolonged HBV persistence after HI depends on the specific backbone of the vector
      carrying HBV genome and the genetic background of the mouse strain. We asked
      whether a genetically closely related hepadnavirus, woodchuck hepatitis virus
      (WHV), may maintain the gene expression and replication in the mouse liver after
      HI. Interestingly, we found that HI of pBS-WHV1.3 containing a 1.3 fold
      overlength WHV genome in BALB/c mouse led to the long presence of WHV DNA and WHV
      proteins expression in the mouse liver. Thus, we asked whether WHV genome
      carrying foreign DNA sequences could maintain the long term gene expression and
      persistence. For this purpose, the coding region of HBV surface antigen (HBsAg)
      was inserted into the WHV genome to replace the corresponding region. Three
      recombinant WHV-HBV genomes were constructed with the replacement with HBsAg a
      determinant, major HBsAg, and middle HBsAg. Serum HBsAg, viral DNA, hepatic WHV
      protein expression, and viral replication intermediates were detected in mice
      after HI with recombinant genomes. Similarly, the recombinant genomes could
      persist for a prolonged period of time up to 45 weeks in mice. WHV and
      recombinant WHV-HBV genomes did not trigger effective antibody and T-cell
      responses to viral proteins. The ability of recombinant WHV constructs to persist
      in mice is an interesting aspect for the future investigation and may be explored
      for in vivo gene transfer. 

PMID- 25942394
TI  - Modification of N staging systems for penile cancer: a more precise prediction of
      prognosis.
AB  - BACKGROUND: The tumour-node-metastasis (TNM) classification is the most widely
      used tool for penile cancer. However, the current system is based on few studies
      and has been unchanged since 2009. We determined whether a modified pathological
      N staging system that incorporates the laterality and number of lymph node
      metastases (LNMs) increases the accuracy of the results in predicting survival
      compared with the 7th edition of the pathological N staging system of the
      American Joint Committee on Cancer (AJCC) for penile cancer. METHODS: The
      clinical and histopathologic data from 111 patients with penile cancer with LNMs
      were analysed. Univariate and multivariate Cox proportional hazard regression
      analyses were used to determine the impact of the clinical and pathological
      factors on disease-specific survival of these patients. The predictive accuracy
      was further assessed using the concordance index. RESULTS: According to the 7th
      edition of the pathological N classification, the 3-year disease-specific
      survival (DSS) rates for patients with pN1, pN2, and pN3 disease are 89.6%,
      65.9%, and 33.6%, respectively (P(N1-N2)=0.030, P(N2-N3)<0.001, P<0.001). Under
      the modified pathological N category criteria, the 3-year DSS rates for pN1, pN2,
      and pN3 patients were 90.7%, 60.5%, and 31.4%, respectively (P(N1-N2)=0.005, P(N2
      N3)=0.004, P<0.001). In separate multivariate Cox regression models, only
      modified N stages (hazard ratio: 4.877, 10.895; P=0.018, P<0.001) exhibited
      independent effects on the outcome. The accuracy of the modified pathological N
      category was significantly increased. CONCLUSIONS: The modified pathological N
      staging system is a better reflection of the prognosis of patients with penile
      cancer. Our study should contribute to the improvement of prognostic
      stratification and systemic treatment to avoid overtreatment of patients.

PMID- 25942395
TI  - Effect of specialized diagnostic assessment units on the time to diagnosis in
      screen-detected breast cancer patients.
AB  - BACKGROUND: The duration of the cancer diagnostic process has considerable
      influence on patients' psychosocial well-being. Breast diagnostic assessment
      units (DAUs) in Ontario, Canada are designed to improve the quality and
      timeliness of care during a breast cancer diagnosis. We compared the diagnostic
      duration of patients diagnosed through a DAU vs usual care (UC). METHODS:
      Retrospective population-based cohort study of 2499 screen-detected breast
      cancers (2011) using administrative health-care databases linked to the Ontario
      Cancer Registry. The diagnostic interval was measured from the initial screen to
      cancer diagnosis. Diagnostic assessment unit use was based on the biopsy and/or
      surgery hospital. We compared the length of the diagnostic interval between the
      DAU groups using multivariable quantile regression. RESULTS: Diagnostic
      assessment units had a higher proportion of patients diagnosed within the 7-week
      target compared with UC (79.1% vs 70.2%, P<0.001). The median time to diagnosis
      at DAUs was 26 days, which was 9 days shorter compared with UC (95% CI: 6.4
      11.6). This effect was reduced to 8.3 days after adjusting for all study
      covariates. Adjusted DAU differences were similar at the 75th and 90th
      percentiles of the diagnostic interval distribution. CONCLUSIONS: Diagnosis
      through an Ontario DAU was associated with a reduced time to diagnosis for screen
      detected breast cancer patients, which likely reduces the anxiety and distress
      associated with waiting for a diagnosis.

PMID- 25942396
TI  - Interleukin-8 is a key mediator of FKBP51-induced melanoma growth, angiogenesis
      and metastasis.
AB  - BACKGROUND: FKBP51 is overexpressed in melanoma and impacts tumour cell
      properties. However, its comprehensive role in melanoma pathogenesis and
      underlying mechanism(s) remain elusive. METHODS: FKBP51 was stably silenced in
      aggressive melanoma cell lines and its effect examined in vitro and in mouse
      model. Histological/immunohistochemical analyses were performed to confirm
      metastasis, angiogenesis and neutrophil infiltration. Gene expression was
      analyzed by qRT-PCR, immunoblot and/or ELISA. NF-kappaB transcriptional activity
      and promoter binding were monitored by luciferase-based promoter-reporter and
      ChIP assays, respectively. Interleukin (IL)-8 inhibition was achieved by gene
      silencing or neutralising-antibody treatment. RESULTS: FKBP51 silencing reduced
      melanoma growth, metastasis, angiogenesis and neutrophil infiltration and led to
      IL-8 downregulation through NF-kappaB suppression in cell lines and tumour
      xenografts. IL-8 inhibition drastically decreased growth, migration and
      invasiveness of FKPB51-overexpressing cells; whereas its treatment partially
      restored the suppressed phenotypes of FKBP51-silenced melanoma cells. Interleukin
      8 depletion in conditioned medium (CM) of FKBP51-overexpressing melanoma cells
      inhibited endothelial cell proliferation and capillary-like structure formation,
      whereas its treatment promoted these effects in endothelial cells cultured in CM
      of FKBP51-silenced melanoma cells. CONCLUSIONS: FKBP51 promotes melanoma growth,
      metastasis and angiogenesis, and IL-8 plays a key role in these processes. Thus,
      targeting of FKBP51 or its upstream or downstream regulatory pathways could lead
      to effective therapeutic strategies against melanoma.

PMID- 25942397
TI  - Intratumoral tertiary lymphoid organ is a favourable prognosticator in patients
      with pancreatic cancer.
AB  - BACKGROUND: Host immunity has critical roles in tumour surveillance. Tertiary
      lymphoid organs (TLOs) are induced in various inflamed tissues. The aim of this
      study was to investigate the clinicopathological and pathobiological
      characteristics of tumour microenvironment in pancreatic ductal carcinoma (PDC)
      with TLOs. METHODS: We examined 534 PDCs to investigate the clinicopathological
      impact of TLOs and their association with tumour-infiltrating immune cells, the
      cytokine milieu, and tissue characteristics. RESULTS: There were two different
      localisations of PDC-associated TLOs, intratumoral and peritumoral. A better
      outcome was observed in patients with intratumoral TLOs, and this was independent
      of other survival factors. The PDC tissues with intratumoral TLOs showed
      significantly higher infiltration of T and B cells and lower infiltration of
      immunosuppressive cells, as well as significantly higher expression of Th1- and
      Th17-related genes. Tertiary lymphoid organs developed with an association with
      arterioles, venules, and nerves. These structures were reduced in an association
      with cancer invasion in PDC tissues, except for those with intratumoral TLOs. The
      PDC tissues with intratumoral TLOs had capillaries consisting of mature
      endothelial cells covered by pericytes. CONCLUSIONS: Our results suggest that the
      presence of intratumoral TLOs represents a microenvironment that has an active
      immune reaction, and shows a relatively intact vascular network retained.

PMID- 25942398
TI  - (18)F-fluorodeoxyglucose positron-emission tomography-computed tomography to
      diagnose recurrent cancer.
AB  - BACKGROUND: Sometimes the diagnosis of recurrent cancer in patients with a
      previous malignancy can be challenging. This prospective cohort study assessed
      the clinical utility of (18)F-fluorodeoxyglucose positron-emission tomography
      computed tomography ((18)F-FDG PET-CT) in the diagnosis of clinically suspected
      recurrence of cancer. METHODS: Patients were eligible if cancer recurrence (non
      small-cell lung (NSCL), breast, head and neck, ovarian, oesophageal, Hodgkin's or
      non-Hodgkin's lymphoma) was suspected clinically, and if conventional imaging was
      non-diagnostic. Clinicians were asked to indicate their management plan before
      and after (18)F-FDG PET-CT scanning. The primary outcome was change in planned
      management after (18)F-FDG PET-CT. RESULTS: Between April 2009 and June 2011, 101
      patients (age, median 65 years; 55% female) were enroled from four cancer centres
      in Ontario, Canada. Distribution by primary tumour type was: NSCL (55%), breast
      (19%), ovarian (10%), oesophageal (6%), lymphoma (6%), and head and neck (4%). Of
      the 99 subjects who underwent (18)F-FDG PET-CT, planned management changed after
      (18)F-FDG PET-CT in 52 subjects (53%, 95% confidence interval (CI), 42-63%); a
      major change in plan from no treatment to treatment was observed in 38 subjects
      (38%, 95% CI, 29-49%), and was typically associated with (18)F-FDG PET-CT
      findings that were positive for recurrent cancer (37 subjects). After 3 months,
      the stated post-(18)F-FDG PET-CT management plan was actually completed in 88
      subjects (89%, 95% CI, 81-94%). CONCLUSION: In patients with suspected cancer
      recurrence and conventional imaging that is non-diagnostic, (18)F-FDG PET-CT
      often provides new information that leads to important changes in patient
      management.

PMID- 25942399
TI  - BRAF and RAS mutations as prognostic factors in metastatic colorectal cancer
      patients undergoing liver resection.
AB  - BACKGROUND: Despite major advances in the management of metastatic colorectal
      cancer (mCRC) with liver-only involvement, relapse rates are high and reliable
      prognostic markers are needed. METHODS: To assess the prognostic impact of BRAF
      and RAS mutations in a large series of liver-resected patients, medical records
      of 3024 mCRC patients were reviewed. Eligible cases undergoing potentially
      curative liver resection were selected. BRAF and RAS mutational status was tested
      on primary and/or metastases by means of pyrosequencing and mass spectrometry
      genotyping assay. Primary endpoint was relapse-free survival (RFS). RESULTS: In
      the final study population (N=309) BRAF mutant, RAS mutant and all wild-type (wt)
      patients were 12(4%), 160(52%) and 137(44%), respectively. Median RFS was 5.7,
      11.0 and 14.4 months respectively and differed significantly (Log-rank, P=0.043).
      At multivariate analyses, BRAF mutant had a higher risk of relapse in comparison
      to all wt (multivariate hazard ratio (HR)=2.31; 95% CI, 1.09-4.87; P=0.029) and
      to RAS mutant (multivariate HR=2.06; 95% CI, 1.02-4.14; P=0.044). Similar results
      were obtained in terms of overall survival. Compared with all wt patients, RAS
      mutant showed a higher risk of death (HR=1.47; 95% CI, 1.05-2.07; P=0.025), but
      such effect was lost at multivariate analyses. CONCLUSIONS: BRAF mutation is
      associated with an extremely poor median RFS after liver resection and with
      higher probability of relapse and death. Knowledge of BRAF mutational status may
      optimise clinical decision making in mCRC patients potentially candidate to
      hepatic surgery. RAS status as useful marker in this setting might require
      further studies.

PMID- 25942400
TI  - Perioperative myocardial injury after adult heart transplant: determinants and
      prognostic value.
AB  - BACKGROUND AND AIM OF THE STUDY: Implications of Cardiac troponin (cTnI) release
      after cardiac transplantation are still unclear. This study disclosed risk
      factors and prognostic implication of cTnI early levels in a single centre cohort
      operated on between January 1999 and December 2010. METHODS: Data on 362
      consecutive recipients (mean age: 47.8+/-13.7, 20.2% female, 18.2% diabetics,
      22.1% with previous cardiac operations, 27.6% hospitalized, 84.9+/-29.4 ml/min
      preoperative glomerular filtration rate) were analyzed using multivariable
      logistic regression modeling. Target outcomes were determinants of troponin
      release, early graft failure (EGF), acute kidney injury (AKI) and operative
      death. RESULTS: Mean cTnI release measured 24 hours after transplant was 10.9+/
      11.6 MUg/L. Overall hospital mortality was 10.8%, EGF 10.5%, and AKI was 12.2%.
      cTnI release>10 MUg/L proved an independent predictor of EGF (OR 2.2; 95% CI,
      1.06-4.6) and AKI (OR 1.031; 95% CI, 1.001-1.064). EGF, in turn, proved a
      determinant of hospital mortality. Risk factors for cTnI>10 MUg/L release were:
      status 2B (OR 0.35; 95% CI, 0.18-0.69, protective), duration of the ischemic
      period (OR 1.006; 95% CI, 1.001-1.011), previous cardiac operation (OR 2.9; 95%
      CI, 1.67-5.0), and left ventricular hypertrophy (OR 3.3; 95% CI, 1.9-5.6).
      CONCLUSIONS: Myocardial enzyme leakage clearly emerged as an epiphenomenon of
      more complicated clinical course. The complex interplay between surgical
      procedure features, graft characteristics and recipient end-organ function
      highlights cTnI release as a risk marker of graft failure and acute kidney
      injury. The search for optimal myocardial preservation is still an issue.

PMID- 25942401
TI  - Accuracy of Telehealth-Administered Measures to Screen Language in Spanish
      Speaking Preschoolers.
AB  - INTRODUCTION: There is a critical need for telehealth language screening measures
      for use with Spanish-speaking children because of the shortage of bilingual
      providers and the current lack of psychometrically sound measures that can be
      administered via telehealth. The purpose of the current study was to describe the
      classification accuracy of individual telehealth language screening measures as
      well as the accuracy of combinations of measures used with Spanish-speaking
      preschoolers from rural and underserved areas of the country. MATERIALS AND
      METHODS: This study applied a hybrid telehealth approach that implemented
      synchronous videoconferencing, videocasting, and traditional pen and paper
      measures. Screening measures included a processing efficiency measure (Spanish
      nonword repetition [NWR]), language sampling, and a developmental language
      questionnaire. Eighty-two mostly Spanish-speaking preschool-age children and
      their parents participated. Thirty-four children had language impairment (LI),
      and 48 had typical language development. RESULTS: Although many of the individual
      measures were significantly associated with standardized language scores (r=0.27
      0.55), not one of the measures had classification values of 0.8 or higher, which
      is recommended when screening for LI. However, when NWR scores were combined with
      language sample or parent survey measures, promising classification accuracy
      values that approached or were higher than 0.8 were obtained. CONCLUSIONS: This
      research provides preliminary evidence showing the effectiveness of a hybrid
      telehealth model in screening the language development of Spanish-speaking
      children. A processing efficiency measure, NWR, combined with a parent survey or
      language sample measure can provide informative and accurate diagnostic
      information when screening Spanish-speaking preschool-age children for LI.

PMID- 25942402
TI  - Endoglin (CD105) Silencing Mediated by shRNA Under the Control of Endothelin-1
      Promoter for Targeted Gene Therapy of Melanoma.
AB  - Endoglin (CD105), a transforming growth factor (TGF)-beta coreceptor, and
      endothelin-1, a vasoconstrictor peptide, are both overexpressed in tumor
      endothelial and melanoma cells. Their targeting is therefore a promising
      therapeutic approach for melanoma tumors. The aim of our study was to construct a
      eukaryotic expression plasmid encoding the shRNA molecules against CD105 under
      the control of endothelin-1 promoter and to evaluate its therapeutic potential
      both in vitro in murine B16F10-luc melanoma and SVEC4-10 endothelial cells and in
      vivo in mice bearing highly metastatic B16F10-luc tumors. Plasmid encoding shRNA
      against CD105 under the control of the constitutive U6 promoter was used as a
      control. We demonstrated the antiproliferative and antiangiogenic effects of both
      plasmids in SVEC4-10 cells, as well as a moderate antitumor and pronounced
      antimetastatic effect in B16F10-luc tumors in vivo. Our results provide evidence
      that targeting melanoma with shRNA molecules against CD105 under the control of
      endothelin-1 promoter is a feasible and effective treatment, especially for the
      reduction of metastatic spread. 

PMID- 25942404
TI  - Uniform Local Binary Pattern Based Texture-Edge Feature for 3D Human Behavior
      Recognition.
AB  - With the rapid development of 3D somatosensory technology, human behavior
      recognition has become an important research field. Human behavior feature
      analysis has evolved from traditional 2D features to 3D features. In order to
      improve the performance of human activity recognition, a human behavior
      recognition method is proposed, which is based on a hybrid texture-edge local
      pattern coding feature extraction and integration of RGB and depth videos
      information. The paper mainly focuses on background subtraction on RGB and depth
      video sequences of behaviors, extracting and integrating historical images of the
      behavior outlines, feature extraction and classification. The new method of 3D
      human behavior recognition has achieved the rapid and efficient recognition of
      behavior videos. A large number of experiments show that the proposed method has
      faster speed and higher recognition rate. The recognition method has good
      robustness for different environmental colors, lightings and other factors.
      Meanwhile, the feature of mixed texture-edge uniform local binary pattern can be
      used in most 3D behavior recognition. 

PMID- 25942403
TI  - Hypertriglyceridemia Is Independently Associated with Renal, but Not Retinal
      Complications in Subjects with Type 2 Diabetes: A Cross-Sectional Analysis of the
      Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study.
AB  - OBJECTIVE: Atherogenic dyslipidemia seems to play a major role in microvascular
      complications and in residual microvascular risk after statin therapy, which
      reduces triglycerides up to 40%. We assessed whether raised TG levels are
      associated with an increased burden from microvascular complications in patients
      with type 2 diabetes. METHODS: Subjects from the Renal Insufficiency And
      Cardiovascular Events (RIACE) Italian Multicentre Study (n=15,773) were divided
      in 4 groups depending on whether they had plasma triglycerides below (NTG, 67.8%)
      or above (HTG, 32.2%) 1.7 mmol/L and were (42.4%) or not on (57.6%) statin
      therapy. Estimated GFR (eGFR) was calculated from serum creatinine, albuminuria
      was measured by immunonephelometry or immunoturbidimetry, and retinopathy was
      evaluated by fundus examination. RESULTS: HTG subjects, either with or without
      statin, had higher prevalence of albuminuria, reduced eGFR and chronic kidney
      disease (CKD), especially the albuminuric forms, but not of retinopathy, than NTG
      subjects. In contrast, cardiovascular disease and advanced DR were more prevalent
      in subjects on statin than in those not, independently of triglyceride levels.
      Logistic regression analysis confirmed that HTG, without or with statin, was
      independently associated with micro and macroalbuminuria, mildly to severely
      reduced eGFR, and all CKD phenotypes, but not with retinopathy. The adjusted odd
      ratios for CKD increased linearly for every 0.26 mmol/L increase (approximately
      one decile) in triglyceride levels. The increase was higher with increasing
      severity of albuminuria, eGFR loss and CKD phenotype as well as in subjects
      receiving than in those not receiving statin treatment. CONCLUSIONS:
      Triglycerides are associated with CKD, but not retinopathy in subjects with type
      2 diabetes, independently of statin treatment. These data point to a possible
      role of hypertriglyceridemia in the development of CKD, though it remains to be
      demonstrated that diabetic individuals might benefit from triglyceride reduction
      with statins and eventually with combination therapy with fibrates. TRIAL
      REGISTRATION: www.ClinicalTrials.gov NCT00715481.

PMID- 25942405
TI  - Pushing the envelope of in situ transmission electron microscopy.
AB  - Recent major improvements to the transmission electron microscope (TEM) including
      aberration-corrected electron optics, light-element-sensitive analytical
      instrumentation, sample environmental control, and high-speed and sensitive
      direct electron detectors are becoming more widely available. When these advances
      are combined with in situ TEM tools, such as multimodal testing based on
      microelectromechanical systems, key measurements and insights on nanoscale
      material phenomena become possible. In particular, these advances enable
      metrology that allows for unprecedented correlation to quantum mechanics and the
      predictions of atomistic models. In this Perspective, we provide a summary of
      recent in situ TEM research that has leveraged these new TEM capabilities as well
      as an outlook of the opportunities that exist in the different areas of in situ
      TEM experimentation. Although these advances have improved the spatial and
      temporal resolution of TEM, a critical analysis of the various in situ TEM fields
      reveals that further progress is needed to achieve the full potential of the
      technology. 

PMID- 25942406
TI  - HO + OClO Reaction System: Featuring a Barrierless Entrance Channel with Two
      Transition States.
AB  - Chlorine-containing compounds play a significant role in the troposphere and are
      key players in the stratosphere. The free radical compound OClO reacts with HO
      free radicals, but the existing experimental kinetics data are limited and
      uncertain. In the present theoretical investigation, the reaction mechanism, rate
      constants, and product branching ratios for the HO + OClO reaction system were
      computed over wide temperature and pressure ranges and compared with the existing
      experimental data. Stationary points on the singlet potential energy surface
      (PES) were calculated at high levels of theory, and the kinetics parameters were
      computed using several methods, including variational transition state theory
      (VTST) and RRKM/master equation techniques. The computed PES is in reasonable
      agreement with previous calculations, and the computed rate constants and
      branching ratio are in good agreement with the recent experiments. The results
      are used as the basis for recommendations for atmospheric chemistry modeling. The
      PES along the reaction path forming the peroxy bond has a steplike structure and
      only a very weakly bound prereactive complex, and yet it still supports two
      transition states along the reaction path. This feature may also be present in
      other reactions in which electrostatic forces align the approaching reactants in
      an unfavorable orientation at long distances, thus requiring a dramatic geometry
      change before reaction can take place. 

PMID- 25942407
TI  - The perils of adapting to dose errors in radiation therapy.
AB  - We consider adaptive robust methods for lung cancer that are also dose-reactive,
      wherein the treatment is modified after each treatment session to account for the
      dose delivered in prior treatment sessions. Such methods are of interest because
      they potentially allow for errors in the delivered dose to be corrected as the
      treatment progresses, thereby ensuring that the tumor receives a sufficient dose
      at the end of the treatment. We show through a computational study with real lung
      cancer patient data that while dose reaction is beneficial with respect to the
      final dose distribution, it may lead to exaggerated daily underdose and overdose
      relative to non-reactive methods that grows as the treatment progresses. However,
      by combining dose reaction with a mechanism for updating an estimate of the
      uncertainty, the magnitude of this growth can be mitigated substantially. The key
      finding of this paper is that reacting to dose errors - an adaptation strategy
      that is both simple and intuitively appealing - may backfire and lead to
      treatments that are clinically unacceptable. 

PMID- 25942410
TI  - Multifunctional Poly(L-lactide)-Polyethylene Glycol-Grafted Graphene Quantum Dots
      for Intracellular MicroRNA Imaging and Combined Specific-Gene-Targeting Agents
      Delivery for Improved Therapeutics.
AB  - Photoluminescent (PL) graphene quantum dots (GQDs) with large surface area and
      superior mechanical flexibility exhibit fascinating optical and electronic
      properties and possess great promising applications in biomedical engineering.
      Here, a multifunctional nanocomposite of poly(l-lactide) (PLA) and polyethylene
      glycol (PEG)-grafted GQDs (f-GQDs) was proposed for simultaneous intracellular
      microRNAs (miRNAs) imaging analysis and combined gene delivery for enhanced
      therapeutic efficiency. The functionalization of GQDs with PEG and PLA imparts
      the nanocomposite with super physiological stability and stable photoluminescence
      over a broad pH range, which is vital for cell imaging. Cell experiments
      demonstrate the f-GQDs excellent biocompatibility, lower cytotoxicity, and
      protective properties. Using the HeLa cell as a model, we found the f-GQDs
      effectively delivered a miRNA probe for intracellular miRNA imaging analysis and
      regulation. Notably, the large surface of GQDs was capable of simultaneous
      adsorption of agents targeting miRNA-21 and survivin, respectively. The combined
      conjugation of miRNA-21-targeting and survivin-targeting agents induced better
      inhibition of cancer cell growth and more apoptosis of cancer cells, compared
      with conjugation of agents targeting miRNA-21 or survivin alone. These findings
      highlight the promise of the highly versatile multifunctional nanocomposite in
      biomedical application of intracellular molecules analysis and clinical gene
      therapeutics. 

PMID- 25942409
TI  - Immunoassay for Capsular Antigen of Bacillus anthracis Enables Rapid Diagnosis in
      a Rabbit Model of Inhalational Anthrax.
AB  - Inhalational anthrax is a serious biothreat. Effective antibiotic treatment of
      inhalational anthrax requires early diagnosis; the further the disease has
      progressed, the less the likelihood for cure. Current means for diagnosis such as
      blood culture require several days to a result and require advanced laboratory
      infrastructure. An alternative approach to diagnosis is detection of a Bacillus
      anthracis antigen that is shed into blood and can be detected by rapid
      immunoassay. The goal of the study was to evaluate detection of poly-gamma-D
      glutamic acid (PGA), the capsular antigen of B. anthracis, as a biomarker
      surrogate for blood culture in a rabbit model of inhalational anthrax. The mean
      time to a positive blood culture was 26 +/- 5.7 h (mean +/- standard deviation),
      whereas the mean time to a positive ELISA was 22 +/- 4.2 h; P = 0.005 in
      comparison with blood culture. A lateral flow immunoassay was constructed for
      detection of PGA in plasma at concentrations of less than 1 ng PGA/ml. Use of the
      lateral flow immunoassay for detection of PGA in the rabbit model found that
      antigen was detected somewhat earlier than the earliest time point at which the
      blood culture became positive. The low cost, ease of use, and rapid time to
      result of the lateral flow immunoassay format make an immunoassay for PGA a
      viable surrogate for blood culture for detection of infection in individuals who
      have a likelihood of exposure to B. anthracis. 

PMID- 25942408
TI  - Prevalence of celiac disease in latin america: a systematic review and meta
      regression.
AB  - BACKGROUND: Celiac disease (CD) is an immune-mediated enteropathy triggered by
      the ingestion of gluten in susceptible individuals, and its prevalence varies
      depending on the studied population. Given that information on CD in Latin
      America is scarce, we aimed to investigate the prevalence of CD in this region of
      the world through a systematic review and meta-analysis. METHODS AND FINDINGS:
      This was a two-phase study. First, a cross-sectional analysis from 981
      individuals of the Colombian population was made. Second, a systematic review and
      meta-regression analysis were performed following the Preferred Reporting Items
      for Systematic Meta- Analyses (PRISMA) guidelines. Our results disclosed a lack
      of celiac autoimmunity in the studied Colombian population (i.e., anti-tissue
      transglutaminase (tTG) and IgA anti-endomysium (EMA)). In the systematic review,
      72 studies were considered. The estimated prevalence of CD in Latin Americans
      ranged between 0.46% and 0.64%. The prevalence of CD in first-degree relatives of
      CD probands was 5.5%. The coexistence of CD and type 1 diabetes mellitus varied
      from 4.6% to 8.7%, depending on the diagnosis methods (i.e., autoantibodies
      and/or biopsies). CONCLUSIONS: Although CD seems to be a rare condition in
      Colombians; the general prevalence of the disease in Latin Americans seemingly
      corresponds to a similar scenario observed in Europeans.

PMID- 25942411
TI  - Living cells or collagen matrix: which is more beneficial in the treatment of
      diabetic foot ulcers?
AB  - In a randomized multicenter study, 26 subjects with diabetes, neuropathy, and
      foot ulceration were treated with standard local wound care and application of
      either a living skin equivalent [LSE] (Dermagraft(r), Advanced BioHealing, La
      Jolla, Calif) or extracellular matrix [ECM] collagen wound dressing (OASIS(r)
      Wound Matrix, Healthpoint, Fort Worth, Tex). Subjects were analyzed to confirm
      that the wounds, demographics, and health characteristics of subjects in each
      group were equivalent. Depending on the randomization, subjects received up to 3
      applications of LSE or 8 applications of ECM. Subjects received this treatment in
      conjunction with standard saline dressings for a maximum of 12 weeks, and were
      observed for 20 weeks. No statistically significant difference was found in the
      size, distribution, or characteristics of the wounds evaluated in each group.
      There was no statistically significant difference in the time to closure or the
      rate of closure between the two groups. Similarly, no significant adverse events
      were reported in either group. The results of this study show comparable healing
      rates with use of either material. Further, it was hypothesized that both
      collagen and cellular components are necessary, and it is suggested that various
      conditions may make one or the other material more desirable. 

PMID- 25942412
TI  -    Classification, diagnosis, and treatment of diabetic foot ulcers.
AB  - The diabetic foot is one of the most significant complications of diabetes and
      is considered to be a major medical, social, and economic problem worldwide. The
      risk for foot ulceration in patients with diabetes is close to 25% and is also
      closely related to risk of limb amputation. Diabetic neuropathy, limited joint
      mobility, micro- and macroangiopathy, and high plantar pressures have been
      described as the main risk factors for diabetic foot ulceration. Proper diagnosis
      and adequate therapeutic treatment are considered the cornerstones to prevention
      of limb amputation and preservation of quality of life in patients with diabetes.
      The following review focuses on the classification, diagnosis, and current trends
      in the treatment of diabetic foot ulceration. 

PMID- 25942413
TI  - High rates of comorbid conditions in patients with type 2 diabetes and foot
      ulcers.
AB  - Background/Aim. Foot ulceration is one of the most important diabetic
      complications that results in major medical, social, and economic consequences
      for patients, their families, and society as a whole. Previous studies have shown
      increased mortality in patients with diabetes with foot ulcers; however, the
      reason for the high mortality in this group of patients is not known. The aim of
      this cross-sectional study was to investigate prevalence rates of comorbid
      conditions in patients with diabetes and foot ulcers. METHODS: A total of 742
      patients with type 2 diabetes (234 with foot ulcers and 508 without ulcers),
      consecutively attending the outpatient diabetes and diabetic foot clinics of the
      authors' hospital were reviewed. Clinical examination was performed to classify
      ulcers as neuropathic or neuroischemic, microvascular and macrovascular
      complications, as well as laboratory tests that were reviewed from medical
      records. RESULTS: Patients with diabetes with and without foot ulcers did not
      differ significantly in terms of age, sex, smoking habits, glycemic control, and
      prevalence rates of hypertension, dyslipidemia, and cerebrovascular disease.
      Known duration of diabetes was longer (P < 0.001), while the values of body mass
      index (P = 0.03) and creatinine clearance (P = 0.003) were lower in the patients
      with foot ulcers than in those without ulcers. In addition, prevalence rates of
      coronary artery disease (P = 0.005), lower extremity arterial disease (P <
      0.001), retinopathy (P < 0.001), and nephropathy (P = 0.04), were higher in the
      patients with foot ulcers compared to those without ulcers. Additionally,
      duration of diabetes was longer and the prevalence rates of microvascular and
      macrovascular complications as well as hypertension, dyslipidemia, and smoking
      were much higher in the patients with neuroischemic ulcers in comparison to those
      with neuropathic ulcers. CONCLUSION: The high mortality rates in patients with
      diabetes and foot ulcers may be due to the high prevalence rates of comorbid
      conditions, especially coronary artery disease and nephropathy.

PMID- 25942414
TI  -  The influence of gender as a risk factor in diabetic foot ulceration  .
AB  - Objective. In a previous large, prospective trial, 29% of all patients with
      diabetes were shown to ulcerate over a 30-month period. The influence of gender
      on foot ulcers has been controversial, with some studies demonstrating male
      gender as a risk factor, while other studies have shown no difference. The
      authors hypothesized that gender may pose a significant risk factor for the
      development of diabetic foot ulcers. METHODS: A total of 248 patients with
      diabetes were enrolled in a 30-month, multicenter, prospective study. There were
      124 men (M) and 124 women (W). There were no differences between M and W in age
      (59 +/- 12 years [mean +/- SD]) versus 57 +/- 13), duration of diabetes mellitus
      (15 +/- 11 years versus 13 +/- 11), or body mass index (BMI) (30.0 +/- 7.7 versus
      31.3 +/- 6.2). The following known risk factors for diabetic foot ulceration were
      measured in both groups: Neuropathy Disability Score (NDS), Vibration Perception
      Threshold (VPT), Semmes Weinstein Monofilament (SWM), plantar peak foot
      pressures, and subtalar joint (STJ) and first metatarsal joint (MTPJ) mobility.
      RESULTS: Men had higher NDS (13 +/- 8 versus 8 +/- 7, P < 0.0001), VPT (36 +/- 17
      V versus 23 +/- 16, P < 0.0001), SWM (5.9 +/- 1.4 versus 5.9 +/- 1.3, P <0.0001),
      and plantar peak foot pressures (6.4 +/- 3.4 kg/cm2 versus 5.0 +/- 2.3, P <
      0.0001), while women had higher MTPJ mobility (69 +/- 24 degrees versus 77 +/-
      23, P < 0.0001) and STJ mobility (22 +/- 10 degrees versus 26 +/- 8, P < 0.0001).
      Plantar foot ulceration developed in 49 (40%) men compared to 24 (19%) women (P
      <0.0001). However, when men and women were analyzed separately, univariate
      logistical regression analysis yielded similar odds ration (OR) in both groups
      for high NDS (>= 5, M 6.1, W 8.3), high VPT (>= 25 V, M 6.0, W 8.9), SWM (M 6.6,
      W 3.7), high foot pressures (>= 6 kg/cm2, M 2.7, W 3.0), and MTPJ mobility (M
      0.96, W 0.97). CONCLUSION: While women have a lower risk than men for foot
      ulceration, this appears to be the result of less severe neuropathy, increased
      joint mobility, and lower foot pressures. However, once neuropathy or other risk
      factors are present, women were found to have the same risk of developing a foot
      ulceration as men. Therefore, women with risk factors for foot ulceration should
      be considered to be at equal risk as men for developing future problems.

PMID- 25942415
TI  - Use of a Novel Hydrosurgery Device in Surgical Debridement of Difficult-to-heal
      Wounds   .
AB  - Debridement is a fundamental step in the management of all chronic and acute
      cutaneous wounds. VersajetTM Hydrosurgery System (Smith & Nephew, Hull, UK) is a
      novel waterjet dissection device designed to surgically debride difficult wounds.
      The authors used this new system on a variety of difficult chronic and acute
      lesions of different etiology (eg, necrotic infected traumatic and chronic
      wounds, burns, and post-surgical wounds), which were then managed with adequate
      dressings or different wound closure techniques such as skin grafting, use of
      dermal substitutes, negative pressure wound therapy (V.A.C.(r), KCI, San Antonio,
      Tex), or treatment by secondary intention.Debridement can be safely accomplished
      in a brief operating time with sufficient tissue selectivity and eclecticism.
      Satisfactory results often were obtained with a single operating session. After
      debridement, the quality of the wound bed was ideal for accelerating endogenous
      wound healing or maximizing the effectiveness of other therapeutic measures. The
      authors believe this hydrosurgery device (Versajet) is a selective, safe, and
      innovative tool for debridement that allows for better control, can reduce
      collateral damage, and subsequently achieve overall better outcomes than
      conventional debridement techniques. 

PMID- 25942417
TI  - Gadolinium-based Contrast Agent Accumulates in the Brain Even in Subjects without
      Severe Renal Dysfunction: Evaluation of Autopsy Brain Specimens with Inductively
      Coupled Plasma Mass Spectroscopy.
AB  - PURPOSE: To use inductively coupled plasma mass spectroscopy (ICP-MS) to evaluate
      gadolinium accumulation in brain tissues, including the dentate nucleus (DN) and
      globus pallidus (GP), in subjects who received a gadolinium-based contrast agent
      (GBCA). MATERIALS AND METHODS: Institutional review board approval was obtained
      for this study. Written informed consent for postmortem investigation was
      obtained either from the subject prior to his or her death or afterward from the
      subject's relatives. Brain tissues obtained at autopsy in five subjects who
      received a linear GBCA (GBCA group) and five subjects with no history of GBCA
      administration (non-GBCA group) were examined with ICP-MS. Formalin-fixed DN
      tissue, the inner segment of the GP, cerebellar white matter, the frontal lobe
      cortex, and frontal lobe white matter were obtained, and their gadolinium
      concentrations were measured. None of the subjects had received a diagnosis of
      severely compromised renal function (estimated glomerular filtration rate <45
      mL/min/1.73 m(2)) or acute renal failure. Fisher permutation test was used to
      compare gadolinium concentrations between the two groups and among brain regions.
      RESULTS: Gadolinium was detected in all specimens in the GBCA agent group (mean,
      0.25 ug per gram of brain tissue +/- 0.44 [standard deviation]), with
      significantly higher concentrations in each region (P = .004 vs the non-GBCA
      group for all regions). In the GBCA group, the DN and GP showed significantly
      higher gadolinium concentrations (mean, 0.44 ug/g +/- 0.63) than other regions
      (0.12 ug/g +/- 0.16) (P = .029). CONCLUSION: Even in subjects without severe
      renal dysfunction, GBCA administration causes gadolinium accumulation in the
      brain, especially in the DN and GP.

PMID- 25942416
TI  - Occurrence and Comparative Toxicity of Haloacetaldehyde Disinfection Byproducts
      in Drinking Water.
AB  - The introduction of drinking water disinfection greatly reduced waterborne
      diseases. However, the reaction between disinfectants and natural organic matter
      in the source water leads to an unintended consequence, the formation of drinking
      water disinfection byproducts (DBPs). The haloacetaldehydes (HALs) are the third
      largest group by weight of identified DBPs in drinking water. The primary
      objective of this study was to analyze the occurrence and comparative toxicity of
      the emerging HAL DBPs. A new HAL DBP, iodoacetaldehyde (IAL) was identified. This
      study provided the first systematic, quantitative comparison of HAL toxicity in
      Chinese hamster ovary cells. The rank order of HAL cytotoxicity is
      tribromoacetaldehyde (TBAL) ~ chloroacetaldehyde (CAL) > dibromoacetaldehyde
      (DBAL) ~ bromochloroacetaldehyde (BCAL) ~ dibromochloroacetaldehyde (DBCAL) > IAL
      > bromoacetaldehyde (BAL) ~ bromodichloroacetaldehyde (BDCAL) >
      dichloroacetaldehyde (DCAL) > trichloroacetaldehyde (TCAL). The HALs were highly
      cytotoxic compared to other DBP chemical classes. The rank order of HAL
      genotoxicity is DBAL > CAL ~ DBCAL > TBAL ~ BAL > BDCAL>BCAL ~ DCAL>IAL. TCAL was
      not genotoxic. Because of their toxicity and abundance, further research is
      needed to investigate their mode of action to protect the public health and the
      environment.

PMID- 25942418
TI  - Residual or retained gadolinium: practical implications for radiologists and our
      patients.

PMID- 25942419
TI  - Enhancing Change-of-Direction Speed in Soccer Players by Functional Inertial
      Eccentric Overload and Vibration Training.
AB  - PURPOSE: To examine the effects of a novel isoinertial eccentric-overload and
      vibration training (EVT) paradigm on change-of-direction (COD) speed and multiple
      performance tests applicable to soccer. METHODS: Twenty-four young male players
      were assigned to an EVT (n = 12) or conventional combined (CONV, n = 12) group,
      once weekly for 11 wk. EVT consisted of 2 sets of 6-10 repetitions in 5 specific
      and 3 complementary exercises. CONV used comparable volume (2 sets of 6-10 reps
      in 3 sequences of 3 exercises) of conventional combined weight, plyometric, and
      linear speed exercises. Pre- and postintervention tests included 25-m sprint with
      4 * 45 degrees  COD every 5th m (V-cut test), 10- and 30-m sprints, repeat-sprint
      ability, countermovement jump, and hopping (RJ5). RESULTS: Group comparison
      showed very likely to likely better performance for EVT in the COD (effect size
      [ES] = 1.42), 30-m (ES = 0.98), 10-m (ES = 1.17), and average power (ES = 0.69)
      and jump height (ES = 0.69) during RJ5. There was a large (r = -.55) relationship
      between the increase in average hopping power and the reduced V-cut time.
      CONCLUSIONS: As EVT, not CONV, improved not only COD ability but also linear
      speed and reactive jumping, this "proof-of-principle" study suggests that this
      novel exercise paradigm performed once weekly could serve as a viable adjunct to
      improve performance tasks specific to soccer.

PMID- 25942420
TI  - Galectin-3 Overrides PTRF/Cavin-1 Reduction of PC3 Prostate Cancer Cell
      Migration.
AB  - Expression of Caveolin-1 (Cav1), a key component of cell surface caveolae, is
      elevated in prostate cancer (PCa) and associated with PCa metastasis and a poor
      prognosis for PCa patients. Polymerase I and Transcript Release Factor
      (PTRF)/cavin-1 is a cytoplasmic protein required for Cav1-dependent formation of
      caveolae. Expression of PTRF reduces the motility of PC3 cells, a metastatic
      prostate cancer cell line that endogenously expresses abundant Cav1 but no PTRF
      and no caveolae, suggesting a role for non-caveolar Cav1 domains, or Cav1
      scaffolds, in PCa cell migration. Tyrosine phosphorylated Cav1 (pCav1) functions
      in concert with Galectin-3 (Gal3) and the galectin lattice to stabilize focal
      adhesion kinase (FAK) within focal adhesions (FAs) and promote cancer cell
      motility. However, whether PTRF regulation of Cav1 function in PCa cell migration
      is related to Gal3 expression and functionality has yet to be determined. Here we
      show that PTRF expression in PC3 cells reduces FAK stabilization in focal
      adhesions and reduces cell motility without affecting pCav1 levels. Exogenous
      Gal3 stabilized FAK in focal adhesions of PTRF-expressing cells and restored cell
      motility of PTRF-expressing PC3 cells to levels of PC3 cells in a dose-dependent
      manner, with an optimal concentration of 2 ug/ml. Exogenous Gal3 stabilized FAK
      in focal adhesions of Gal3 knockdown PC3 cells but not in Cav1 knockdown PC3
      cells. Cav1 knockdown also prevented Gal3 rescue of FA-associated FAK
      stabilization in PTRF-expressing PC3 cells. Our data support a role for
      PTRF/cavin-1, through caveolae formation, as an attenuator of the non-caveolar
      functionality of Cav1 in Gal3-Cav1 signalling and regulation of focal adhesion
      dynamics and cancer cell migration. 

PMID- 25942422
TI  - Toward a Comprehensive Instrument of Oral Health Literacy in Spanish.
AB  - To develop and assess the Spanish Oral Health Literacy Scale (SOHLS) in a Mexican
      adult population, a repeated survey was undertaken in 227 adults. Participants
      were interviewed and asked to complete the SOHLS on the basis of the Health
      Literacy Test developed by the Educational Testing Service. The SOHLS covered
      literacy skills: location, integration, generation, calculation and return.
      Cronbach's alpha was obtained for internal consistency and intraclass correlation
      coefficient for test-retest reliability. Construct validity was obtained
      comparing the test score with self perceived oral health and the Oral Health
      Impact Profile-14 (OHIP-14). Mean age was 47.2 years (SD = 14.3 years). Average
      time for test completion was 24.6 +/- 11 minutes; mean score was 24.2 +/- 3.8 and
      Cronbach's alpha was .748; the intraclass correlation coefficient was 0.766.
      Spearman's correlation was 0.426 between the test and self perceived oral health.
      Pearson's correlation was -0.336 between the total test score and the OHIP-14.
      The instrument has good values of reliability; construct validity is significant
      but could be improved. 

PMID- 25942421
TI  - Cost-Effectiveness of a Specialist Geriatric Medical Intervention for Frail Older
      People Discharged from Acute Medical Units: Economic Evaluation in a Two-Centre
      Randomised Controlled Trial (AMIGOS).
AB  - BACKGROUND: Poor outcomes and high resource-use are observed for frail older
      people discharged from acute medical units. A specialist geriatric medical
      intervention, to facilitate Comprehensive Geriatric Assessment, was developed to
      reduce the incidence of adverse outcomes and associated high resource-use in this
      group in the post-discharge period. OBJECTIVE: To examine the costs and cost
      effectiveness of a specialist geriatric medical intervention for frail older
      people in the 90 days following discharge from an acute medical unit, compared
      with standard care. METHODS: Economic evaluation was conducted alongside a two
      centre randomised controlled trial (AMIGOS). 433 patients (aged 70 or over) at
      risk of future health problems, discharged from acute medical units within 72
      hours of attending hospital, were recruited in two general hospitals in
      Nottingham and Leicester, UK. Participants were randomised to the intervention,
      comprising geriatrician assessment in acute units and further specialist
      management, or to control where patients received no additional intervention over
      and above standard care. Primary outcome was incremental cost per quality
      adjusted life year (QALY) gained. RESULTS: We undertook cost-effectiveness
      analysis for 417 patients (intervention: 205). The difference in mean adjusted
      QALYs gained between groups at 3 months was -0.001 (95% confidence interval [CI]:
      -0.009, 0.007). Total adjusted secondary and social care costs, including direct
      costs of the intervention, at 3 months were L4412 (?5624, $6878) and L4110
      (?5239, $6408) for the intervention and standard care groups, the incremental
      cost was L302 (95% CI: 193, 410) [?385, $471]. The intervention was dominated by
      standard care with probability of 62%, and with 0% probability of cost
      effectiveness (at L20,000/QALY threshold). CONCLUSIONS: The specialist geriatric
      medical intervention for frail older people discharged from acute medical unit
      was not cost-effective. Further research on designing effective and cost
      effective specialist service for frail older people discharged from acute medical
      units is needed. TRIAL REGISTRATION: ISRCTN registry ISRCTN21800480
      http://www.isrctn.com/ISRCTN21800480.

PMID- 25942423
TI  - Impact of Maternal HIV Seroconversion during Pregnancy on Early Mother to Child
      Transmission of HIV (MTCT) Measured at 4-8 Weeks Postpartum in South Africa 2011
      2012: A National Population-Based Evaluation.
AB  - BACKGROUND: Mother-to-child transmission of HIV (MTCT) depends on the timing of
      HIV infection. We estimated HIV-seroconversion during pregnancy (HSP) after
      having a HIV-negative result antenatally, and its contribution to early MTCT in
      South Africa (SA). METHODS AND FINDINGS: Between August 2011 and March 2012, we
      recruited a nationally representative sample of mother-infant pairs with infants
      aged 4-to-8 weeks from 578 health facilities. Data collection included mother
      interviews, child health-card reviews, and infant dried-blood-spots sample
      (iDBS). iDBS were tested for HIV antibodies and HIV-deoxyribonucleic-acid (HIV
      DNA). HSP was defined as maternal self-report of an HIV-negative test during this
      pregnancy, no documented use of antiretroviral drugs and a matched HIV sero
      positive iDBS. We used 20 imputations from a uniform distribution for time from
      reported antenatal HIV-negative result to delivery to estimate time of HSP. Early
      MTCT was defined based on detection of HIV-DNA in iDBS. Estimates were adjusted
      for clustering, nonresponse, and weighted by SA's 2011 live-births. RESULTS: Of
      9802 mother-infant pairs, 2738 iDBS were HIV sero-positive, including 212 HSP,
      resulting in a nationally weighted estimate of 3.3% HSP (95% Confidence Interval:
      2.8%-3.8%). Median time of HIV-seroconversion was 32.8weeks gestation;28.3%
      (19.7%- 36.9%) estimated to be >36 weeks. Early MTCT was 10.7% for HSP (6.2%
      16.8%) vs. 2.2% (1.7%-2.8%) for mothers with known HIV-positive status. Although
      they represent 2.2% of all mothers and 6.7% of HIV-infected mothers, HSP
      accounted for 26% of early MTCT. Multivariable analysis indicated the highest
      risk for HSP was among women who knew the baby's father was HIV-infected
      (adjusted-hazard ratio (aHR) 4.71; 1.49-14.99), or who had been screened for
      tuberculosis (aHR 1.82; 1.43-2.32). CONCLUSIONS: HSP risk is high and contributes
      significantly to early MTCT. Identification of HSP by repeat-testing at 32 weeks
      gestation, during labor, 6 weeks postpartum, in tuberculosis-exposed women, and
      in discordant couples might reduce MTCT.

PMID- 25942424
TI  - Decline in Coronary Mortality in Sweden between 1986 and 2002: Comparing
      Contributions from Primary and Secondary Prevention.
AB  - BACKGROUND: The relative importance of risk factor reduction in healthy people
      (primary prevention) versus that in patients with coronary heart disease
      (secondary prevention) has been debated. We aimed to quantify the contribution of
      the two. METHODOLOGY: We used the previously validated IMPACT model to estimate
      contributions from primary prevention (reducing risk factors in the population,
      particularly smoking, cholesterol and systolic blood pressure) and from secondary
      prevention (reducing risk factors in coronary heart disease patients) in the
      Swedish population. PRINCIPAL FINDINGS: Between 1986 and 2002, about 8,690 fewer
      deaths were related to changes in the three major risk factors. Population
      cholesterol fell by 0.64 mmol/L, with approximately 5,210 fewer deaths
      attributable to diet changes (4,470 in healthy people740 in patients.) plus 810
      to statin treatment (200 in healthy people, 610 in patients). Overall smoking
      prevalence decreased by 10.3%, resulting in 1,195 fewer deaths, attributable to
      smoking cessation (595 in healthy people, 600 in patients). Mean population
      systolic blood pressure fell by 2.6 mmHg, resulting in 900 fewer deaths (865 in
      healthy people, 35 in patients), plus 575 fewer deaths attributable to
      antihypertensive medication in healthy people. The majority of falls in deaths
      attributable to risk factors occurred in people without known heart disease:
      6,705 fewer deaths compared with 1,985 fewer deaths in patients (secondary
      prevention), emphasizing the importance of promoting health interventions in the
      general population. CONCLUSIONS: The largest effects on mortality came from
      primary prevention, giving markedly larger mortality reductions than secondary
      prevention.

PMID- 25942426
TI  - Direct Observation of Sublimation Behaviors in One-Dimensional In2Se3/In2O3
      Nanoheterostructures.
AB  - Recently, in situ transmission electron microscopy (TEM) has provided a route to
      analyze structural characterization and chemical evolution with its powerful and
      unique applications. In this paper, we disclose the detailed phenomenon of
      sublimation on the atomic scale. In2Se3/In2O3 nanowires were synthesized via the
      vapor-liquid-solid mechanism and studied in an ultra-high-vacuum (UHV) TEM at
      high temperature in real time. During in situ observation of the sublimation
      process of the nanowires, the evolution and reconstruction of the exposed In2Se3
      surface progressed in different manners with time. The surface structure was
      decomposed by mass-desorption and stepwise-migration processes, which are also
      energetically favored processes in the ab initio calculation. This study
      developed a new concept and will be essential in the development of atomic
      kinetics. 

PMID- 25942427
TI  - Decrease in longitudinal strain in heart transplant recipients is associated with
      rejection.
AB  - BACKGROUND: Around 20-40% of heart transplant patients experience moderate to
      severe rejection within the first year after heart transplantation.
      Endomyocardial biopsy (EMB) is a gold standard for diagnosing heart transplant
      rejection. There is a need for non-invasive alternatives that allow for early,
      safe and reliable diagnosis of acute graft rejection prior to the onset of
      clinical symptoms. AIMS: Our aim was to investigate the potential of speckle
      tracking derived strain analysis in the diagnosis of acute graft rejection.
      METHODS: Patients indicated for EMB consented to a trans-thoracic
      echocardiography examination (TTE) within 2 hours of the EMB. Of this cohort,
      those with at least 2 EMBs separated >= 1 week, and whose TTE could be analyzed
      for strain, were included. The relationship between strain and EMB results was
      evaluated. RESULTS: Of the 43 patients included (mean age 51.33+/-1.79, 67%
      male), 23 had findings of rejection identified on at least one EMB and at least
      one EMB without rejection for comparison. A significant deterioration in the
      longitudinal strain during rejection compared to non-rejection was found on
      apical 4-chamber views (-11.51+/-0.91 vs -13.48+/-0.96, P=0.025) and apical 2
      chamber views (-11.84+/-0.78 vs -14.43+/-0.83, P=0.002). In the patients in whom
      no rejection was identified on either EBM, there was no significant change in
      longitudinal strain values at two different time points. CONCLUSION: Worsening of
      longitudinal strain was associated with acute cellular rejection. Routine TTE
      based strain analysis could help in early detection of cardiac rejection and
      timing of EMB.

PMID- 25942425
TI  - Population Genetic Structure Within and among Seasonal Site Types in the Little
      Brown Bat (Myotis lucifugus) and the Northern Long-Eared Bat (M.
      septentrionalis).
AB  - During late summer and early autumn, temperate bats migrate from their summering
      sites to swarming sites, where mating likely occurs. However, the extent to which
      individuals of a single summering site migrate to the same swarming site, and
      vice versa, is not known. We examined the migratory connectivity between
      summering and swarming sites in two temperate, North American, bat species, the
      little brown bat (Myotis lucifugus) and the northern long-eared bat (Myotis
      septentrionalis). Using mitochondrial and microsatellite DNA markers, we examined
      population structuring within and among summering and swarming sites. Both
      species exhibited moderate degrees of mitochondrial DNA differentiation (little
      brown bat: FST(SUMMER) = 0.093, FST(SWARMING) = 0.052; northern long-eared bat:
      FST(SUMMER) = 0.117, FST(SWARMING) = 0.043) and little microsatellite DNA
      differentiation among summering and among swarming sites[corrected]. Haplotype
      diversity was significantly higher at swarming sites than summering sites,
      supporting the idea that swarming sites are comprised of individuals from various
      summering sites. Further, pairwise analyses suggest that swarming sites are not
      necessarily comprised of only individuals from the most proximal summering
      colonies.

PMID- 25942428
TI  - Mortality in patients with TIMI 3 flow after PCI in relation to time delay to
      reperfusion.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) performed within 12 h from
      symptom onset enables complete blood flow restoration in infarct-related artery
      in 90% of patients. Nevertheless, even with complete restoration of epicardial
      blood flow in culprit vessel (postprocedural Thrombolysis in Myocardial
      Infarction (TIMI) flow grade 3), myocardial perfusion at tissue level may be
      insufficient. We hypothesized that the outcome of patients with STEMI/bundle
      branch block (BBB)-myocardial infarction and post-PCI TIMI 3 flow is related to
      the time to reperfusion. METHODS: Observational study based on a retrospective
      analysis of population of 635 consecutive patients with STEMI/BBB-MI and post-PCI
      TIMI 3 flow from January 2009 to December 2011 (mean age 63 years, 69.6% males).
      Mortality of patients was evaluated in relation to the time from symptom onset to
      reperfusion. RESULTS: A total of 83 patients (13.07%) with postprocedural TIMI 3
      flow after PCI had died at 1-year follow-up. Median TD in patients who survived
      was 3.92 h (iqr 5.43), in patients who died 6.0 h (iqr 11.42), P = 0.004.
      Multiple logistic regression analysis identified time delay >= 9 h as
      significantly related to 1-year mortality of patients with STEMI/BBB-MI and post
      PCI TIMI 3 flow (OR 1.958, P = 0.026). Other significant variables associated
      with mortality in multivariate regression analysis were: left ventricle ejection
      fraction < 30% (P = 0.006), age > 65 years (P < 0.001), Killip class >2 (P
      <0.001), female gender (P = 0.019), and creatinine clearance < 30 mL/min (P <
      0.001). CONCLUSION: Time delay to reperfusion is significantly related to 1-year
      mortality of patients with STEMI/BBB-MI and complete restoration of epicardial
      blood flow in culprit vessel after PCI.

PMID- 25942429
TI  - TLR2 and TLR4 expression on CD14(++) and CD14(+) monocyte subtypes in adult-onset
      autoimmune diabetes.
AB  - BACKGROUND: Peripheral blood monocytes are key effectors of innate immunity.
      Dysfunction, changes in their counts or altered expression of cytokines and
      pattern-recognition receptors on monocytes may contribute to the development of
      the autoimmune type of diabetes mellitus (AD). AIMS: We aimed to analyze the
      counts and proportions of the two main subtypes of monocyte cells, CD14(++) and
      CD14(+), and to look for potential changes in the expression of toll-like
      receptors 2 (TLR2) and 4 (TLR4) as well as cytokine prolactin (PRL) in adult
      onset AD, including diabetes mellitus type 1 (T1DM) and latent autoimmune
      diabetes in adults (LADA). METHODS: We examined 21 T1DM patients, 9 patients with
      LADA, 16 control patients with type 2 diabetes mellitus (T2DM) and 24 healthy
      individuals. All diabetic patients were diagnosed after the age of 18 years.
      Expression at the mRNA level was determined by quantitative PCR. Flow cytometry
      was used to ascertain membrane expression and cell counts. RESULTS: T1DM patients
      had fewer CD14(++) (P < 0.01) and CD14(+) (P < 0.0001) monocytes whereas T2DM
      subjects showed decreased counts of CD14(+) monocytes compared to healthy
      controls (P < 0.001). TLR2 protein expression was significantly increased in T1DM
      CD14(+) monocytes compared to healthy controls (P < 0.05), while TLR4 expression
      in T1DM CD14(++) cells was significantly lower (P < 0.0001). There was no
      significant difference between the groups in terms of PRL mRNA expression in
      monocytes. CONCLUSIONS: The observed changes in the proportions of both immune
      cell types and in the expression of functional pattern-recognition receptors on
      monocytes in the subjects examined may arise as a consequence of chronic
      inflammation that accompanies long-term diabetes.

PMID- 25942431
TI  - Graphene nanoplatelets with selectively functionalized edges as electrode
      material for electrochemical energy storage.
AB  - In recent years, graphene-based materials have been in the forefront as electrode
      material for electrochemical energy generation and storage. Despite this
      prevalent interest, synthesis procedures have not attained three important
      efficiency requirements, that is, cost, energy, and eco-friendliness. In this
      regard, in the present work, graphene nanoplatelets with selectively
      functionalized edges (XGnPs) are prepared through a simple, eco-friendly and
      efficient method, which involves ball milling of graphite in the presence of
      hydrogen (H2), bromine (Br2), and iodine (I2). The resultant HGnP, BrGnP, and
      IGnP reveal significant exfoliation of graphite layers, as evidenced by high BET
      surface area of 414, 595, and 772 m(2) g(-1), respectively, in addition to
      incorporation of H, Br, and I along with other oxygen-containing functional
      groups at the graphitic edges. The BrGnP and IGnP are also found to contain 4.12
      and 2.20 at % of Br and I, respectively in the graphene framework. When tested as
      supercapacitor electrode, all XGnPs show excellent electrochemical performance in
      terms of specific capacitance and durability at high current density and long
      term operation. Among XGnPs, IGnP delivers superior performance of 172 F g(-1) at
      1 A g(-1) compared with 150 F g(-1) for BrGnP and 75 F g(-1) for HGnP because the
      large surface area and high surface functionality in the IGnP give rise to the
      outstanding capacitive performance. Moreover, all XGnPs show excellent retention
      of capacitance at high current density of 10 A g(-1) and for long-term operation
      up to 1000 charge-discharge cycles. 

PMID- 25942430
TI  - CSF Proteomics Identifies Specific and Shared Pathways for Multiple Sclerosis
      Clinical Subtypes.
AB  - Multiple sclerosis (MS) is an immune-mediated, neuro-inflammatory, demyelinating
      and neurodegenerative disease of the central nervous system (CNS) with a
      heterogeneous clinical presentation and course. There is a remarkable phenotypic
      heterogeneity in MS, and the molecular mechanisms underlying it remain unknown.
      We aimed to investigate further the etiopathogenesis related molecular pathways
      in subclinical types of MS using proteomic and bioinformatics approaches in
      cerebrospinal fluids of patients with clinically isolated syndrome, relapsing
      remitting MS and progressive MS (n=179). Comparison of disease groups with
      controls revealed a total of 151 proteins that are differentially expressed in
      clinically different MS subtypes. KEGG analysis using PANOGA tool revealed the
      disease related pathways including aldosterone-regulated sodium reabsorption
      (p=8.02x10-5) which is important in the immune cell migration, renin-angiotensin
      (p=6.88x10-5) system that induces Th17 dependent immunity, notch signaling
      (p=1.83x10-10) pathway indicating the activated remyelination and vitamin
      digestion and absorption pathways (p=1.73x10-5). An emerging theme from our
      studies is that whilst all MS clinical forms share common biological pathways,
      there are also clinical subtypes specific and pathophysiology related pathways
      which may have further therapeutic implications. 

PMID- 25942432
TI  - A Qualitative Approach to a Better Understanding of the Problems Underlying Drug
      Shortages, as Viewed from Belgian, French and the European Union's Perspectives.
AB  - The problem of drug shortages has been reported worldwide, gaining prominence in
      multiple domains and several countries in recent years. The aim of the study was
      to analyze, characterise and assess this problem in Belgium and France, while
      also adopting a wider perspective from the European Union. A qualitative
      methodological approach was employed, including semi-structured interviews with
      the representatives of respective national health authorities, pharmaceutical
      companies and wholesalers, as well as hospital and community pharmacists. The
      research was conducted in early 2014. Four themes, which were identified through
      the interviews, were addressed in the paper, i.e. a) defining drug shortages, b)
      their dynamics and perception, c) their determinants, d) the role of the European
      and national institutions in coping with the problem. Three groups of
      determinants of drug shortages were identified throughout this study:
      manufacturing problems, distribution and supply problems, and problems related to
      economic aspects. Currently, the Member States of the European Union are striving
      to resolve the problem very much on their own, although a far more focused and
      dedicated collaboration may well prove instrumental in coping with drug shortages
      throughout Europe more effectively. To the best of the authors' knowledge, this
      is the first qualitative study to investigate the characteristics, key
      determinants, and the problem drivers of drug shortages, focusing on this
      particular group of countries, while also adopting the European Union's
      perspective. 

PMID- 25942433
TI  - Children, computer exposure and musculoskeletal outcomes: the development of
      pathway models for school and home computer-related musculoskeletal outcomes.
AB  - Children's computer use is rapidly growing, together with reports of related
      musculoskeletal outcomes. Models and theories of adult-related risk factors
      demonstrate multivariate risk factors associated with computer use. Children's
      use of computers is different from adult's computer use at work. This study
      developed and tested a child-specific model demonstrating multivariate
      relationships between musculoskeletal outcomes, computer exposure and child
      factors. Using pathway modelling, factors such as gender, age, television
      exposure, computer anxiety, sustained attention (flow), socio-economic status and
      somatic complaints (headache and stomach pain) were found to have effects on
      children's reports of musculoskeletal symptoms. The potential for children's
      computer exposure to follow a dose-response relationship was also evident.
      Developing a child-related model can assist in understanding risk factors for
      children's computer use and support the development of recommendations to
      encourage children to use this valuable resource in educational, recreational and
      communication environments in a safe and productive manner. PRACTITIONER SUMMARY:
      Computer use is an important part of children's school and home life. Application
      of this developed model, that encapsulates related risk factors, enables
      practitioners, researchers, teachers and parents to develop strategies that
      assist young people to use information technology for school, home and leisure in
      a safe and productive manner.

PMID- 25942434
TI  - Efficacy of a contact lens sensor for monitoring 24-h intraocular pressure
      related patterns.
AB  - PURPOSE: To study performance of a contact lens sensor (CLS) for 24-hour
      monitoring of IOP-related short-term patterns and compare with IOP obtained by
      pneumatonometry. METHODS: Prospective clinical trial. Thirty-one healthy
      volunteers and 2 glaucoma patients were housed for 24 hours in a sleep
      laboratory. One randomly selected eye was fitted with a CLS (Triggerfish,
      Sensimed, Switzerland), which measures changes in ocular circumference. In the
      contralateral eye, IOP measurements were taken using a pneumatonometer every two
      hours with subjects in the habitual body positions. Heart rate (HR) was measured
      3 times during the night for periods of 6 minutes separated by 2 hours.
      Performance of CLS was defined in two ways: 1) recording the known pattern of IOP
      increase going from awake (sitting position) to sleep (recumbent), defined as the
      wake/sleep (W/S) slope and 2) accuracy of the ocular pulse frequency (OPF)
      concurrent to that of the HR interval. Strength of association between overall
      CLS and pneumatonometer curves was assessed using coefficients of determination
      (R2). RESULTS: The W/S slope was statistically significantly positive in both
      eyes of each subject (CLS, 57.0 +/- 40.5 mVeq/h, p<0.001 and 1.6 +/- 0.9 mmHg/h,
      p<0.05 in the contralateral eye). In all, 87 CLS plots concurrent to the HR
      interval were evaluated. Graders agreed on evaluability for OPF in 83.9% of CLS
      plots. Accuracy of the CLS to detect the OPF was 86.5%. Coefficient of
      correlation between CLS and pneumatonometer for the mean 24-h curve was R2 =
      0.914. CONCLUSIONS: CLS measurements compare well to the pneumatonometer and may
      be of practical use for detection of sleep-induced IOP changes. The CLS also is
      able to detect ocular pulsations with good accuracy in a majority of eyes. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01390779.

PMID- 25942435
TI  - Socioeconomic position, type 2 diabetes and long-term risk of death.
AB  - BACKGROUND: Both socioeconomic position (SEP) and type 2 diabetes have previously
      been found to be associated with mortality; however, little is known about the
      association between SEP, type 2 diabetes and long-term mortality when comorbidity
      is taken into account. METHODS: We conducted a population-based cohort study of
      all Danish citizens aged 40-69 years with no history of diabetes during 2001-2006
      (N=2,330,206). The cohort was identified using nationwide registers, and it was
      followed for up to 11 years (mean follow-up was 9.5 years (SD: 2.6)). We
      estimated the age-standardised mortality rate (MR) and performed Poisson
      regression to estimate the mortality-rate-ratio (MRR) by educational level,
      income and cohabiting status among people with and without type 2 diabetes.
      RESULTS: We followed 2,330,206 people for 22,971,026 person-years at risk and
      identified 139,681 individuals with type 2 diabetes. In total, 195,661 people
      died during the study period; 19,959 of these had type 2 diabetes. The age
      standardised MR increased with decreasing SEP both for people with and without
      diabetes. Type 2 diabetes and SEP both had a strong impact on the overall
      mortality; the combined effect of type 2 diabetes and SEP on mortality was
      additive rather than multiplicative. Compared to women without diabetes and in
      the highest income quintile, the MRR's were 2.8 (95%CI 2.6, 3.0) higher for women
      with type 2 diabetes in the lowest income quintile, while diabetes alone
      increased the risk of mortality 2.0 (95%CI 1.9, 2.2) times and being in the
      lowest income quintile without diabetes 1.8 (95%CI 1.7,1.9) times after adjusting
      for comorbidity. For men, the MRR's were 2.7 (95%CI 2.5,2.9), 1.9 (95%CI 1.8,2.0)
      and 1.8 (95%CI 1.8,1.9), respectively. CONCLUSION: Both Type 2 diabetes and SEP
      were associated with the overall mortality. The relation between type 2 diabetes,
      SEP, and all-cause mortality was only partly explained by comorbidity.

PMID- 25942436
TI  - Oxidative markers of Myeloperoxidase and Catalase and their diagnostic
      performance in bipolar disorder.
AB  - BACKGROUND: Recent researches suggest oxidative stress and generalized
      inflammatory state to be associated with bipolar I disorder (BID). Our aim is to
      evaluate Myeloperoxidase (MPO) and Catalase (CAT) activities in BID. METHODS: 73
      BID patients and 73 healthy controls were enrolled. Patients were classified into
      manic, depressive and euthymic state. Serum MPO and CAT were measured in both
      patients and controls. RESULTS: CAT activity was significantly lower in controls
      than manic, depressive and euthymics (p<0.001). MPO activity was significantly
      higher in controls compared to euthymics (p=0.007) and it was significantly
      higher in depressives compared to euthymics (p=0.023). CAT was negatively and MPO
      was positively correlated with disease duration in overall the patients. Positive
      Predictive Value was 94.5% and Negative Predictive Value was 100% above the
      cutoff point for CAT activity. CONCLUSION: MPO and CAT activities are impaired in
      BID, which may be associated with oxidative stress and inflammation.

PMID- 25942437
TI  - Sexual dysfunction in arterial hypertension women: The role of depression and
      anxiety.
AB  - INTRODUCTION: Although high blood pressure is known to be associated with sexual
      dysfunction, this phenomenon has been little studied in females and has received
      little intervention in clinical practice. OBJECTIVE: To identify the presence of
      sexual dysfunction, considering the different possible domains and to evaluate
      its relationship with the presence of symptoms of anxiety and depression in women
      with arterial hypertension. METHODOLOGY: One hundred fifty seven women (from 56.4
      years) with a diagnosis of arterial hypertension were evaluated with media
      through the Female Sexual Function Index (FSFI) and the Hospital Anxiety and
      Depression Scale (HADS). RESULTS: High rates of sexual dysfunction were detected
      in the women evaluated, and this dysfunction was in all domains as follows:
      desire (68.2%), excitement (68.2%), lubrication (41.1%), orgasm (55.4%),
      satisfaction (66.42%) and pain (56.1%). Elevated rates of symptoms of anxiety
      (43.3%) and depression (26.8%) were also found in our sample. Nevertheless, in
      the present study, such symptoms showed no relationship with sexual dysfunction
      levels for any of the domains assessed. CONCLUSION: Hypertensive patients exhibit
      an elevated presence of sexual dysfunction, as well as anxious and depressive
      symptoms. Although the literature on female sexuality indicates influences of
      these symptoms on sexual functions, this study did not identify such a
      relationship in the studied population. Sexuality is an important element in
      patient quality of life, and a broad understanding of female sexual function is
      fundamental for good follow-up in these patients.

PMID- 25942438
TI  - Leveraging the power of high performance computing for next generation sequencing
      data analysis: tricks and twists from a high throughput exome workflow.
AB  - Next generation sequencing (NGS) has been a great success and is now a standard
      method of research in the life sciences. With this technology, dozens of whole
      genomes or hundreds of exomes can be sequenced in rather short time, producing
      huge amounts of data. Complex bioinformatics analyses are required to turn these
      data into scientific findings. In order to run these analyses fast, automated
      workflows implemented on high performance computers are state of the art. While
      providing sufficient compute power and storage to meet the NGS data challenge,
      high performance computing (HPC) systems require special care when utilized for
      high throughput processing. This is especially true if the HPC system is shared
      by different users. Here, stability, robustness and maintainability are as
      important for automated workflows as speed and throughput. To achieve all of
      these aims, dedicated solutions have to be developed. In this paper, we present
      the tricks and twists that we utilized in the implementation of our exome data
      processing workflow. It may serve as a guideline for other high throughput data
      analysis projects using a similar infrastructure. The code implementing our
      solutions is provided in the supporting information files. 

PMID- 25942439
TI  - Quantitative Trait Loci and Candidate Genes for Neutrophil Recruitment in Sterile
      Inflammation Mapped in AXB-BXA Recombinant Inbred Mice.
AB  - Neutrophil recruitment (NR) to sites of sterile inflammation plays a key role in
      tissue damage and healing potential of lesions characteristic to non-infectious
      inflammatory diseases. Previous studies suggested significant genetic control of
      neutrophil survival, function, and migration in inflammatory responses to
      endogenous and exogenous stimuli. We have mapped the murine genome for
      quantitative trait loci (QTLs) harbouring genetic determinants that regulate NR
      in SI using a murine model of chemically-induced peritonitis. NR was quantified
      in 16 AXB-BXA recombinant inbred strains and their progenitors, A/J (A) and
      C57BL/6J (B). A continuous distribution of NR was found among the strains, with
      parent B showing higher NR and parent A showing lower NR (3.0-fold difference,
      p=0.05). Within the progeny strains, a 5.5-fold difference in NR was observed
      between the lowest, BXA1, and the highest responders AXB19 (p<0.001). This data
      was analyzed using GeneNetwork, which linked NR to one significant QTL on
      chromosome 12 (Peritoneal Neutrophil Recruitment 1, PNR1) and two suggestive QTLs
      (PNR2, PNR3) on chromosomes 12 and 16 respectively. Sixty-four candidate genes
      within PNR1 were cross-referenced with currently published data, mRNA expression
      from two NR microarrays, and single nucleotide polymorphism analysis. The present
      study brings new light into the genetics of NR in response to cell injury and
      highlights potential candidate genes Hif1alpha, Fntb, and Prkch and their
      products for further studies on neutrophil infiltration and inflammation
      resolution in sterile inflammation. 

PMID- 25942441
TI  - Flicker Noise as a Probe of Electronic Interaction at Metal-Single Molecule
      Interfaces.
AB  - Charge transport properties of metal-molecule interfaces depend strongly on the
      character of molecule-electrode interactions. Although through-bond coupled
      systems have attracted the most attention, through-space coupling is important in
      molecular systems when, for example, through-bond coupling is suppressed due to
      quantum interference effects. To date, a probe that clearly distinguishes these
      two types of coupling has not yet been demonstrated. Here, we investigate the
      origin of flicker noise in single molecule junctions and demonstrate how the
      character of the molecule-electrode coupling influences the flicker noise
      behavior of single molecule junctions. Importantly, we find that flicker noise
      shows a power law dependence on conductance in all junctions studied with an
      exponent that can distinguish through-space and through-bond coupling. Our
      results provide a new and powerful tool for probing and understanding coupling at
      the metal-molecule interface. 

PMID- 25942440
TI  - Antiviral Effects of Novel Herbal Medicine KIOM-C, on Diverse Viruses.
AB  - In order to identify new potential antiviral agents, recent studies have
      advocated thorough testing of herbal medicines or natural substances that are
      traditionally used to prevent viral infections. Antiviral activities and the
      mechanism of action of the total aqueous extract preparation of KIOM-C, a novel
      herbal medicine, against diverse types of viruses were investigated. In vitro
      antiviral activity against A/Puerto Rico/8/34 (H1N1) (PR8), vesicular stomatitis
      virus (VSV), and Newcastle disease virus (NDV) through the induction of type-I
      interferon related protein phosphorylation and up-regulation of pro-inflammatory
      cytokines in murine macrophage cells (RAW264.7) were determined. In vivo, KIOM-C
      treated BALB/c mice showed higher survivability and lower lung viral titers when
      challenged with A/Aquatic bird/Korea/W81/2005 (H5N2), A/PR/8/34(H1N1), A/Aquatic
      bird/Korea/W44/2005(H7N3) or A/Chicken/Korea/116 /2004(H9N2) influenza subtypes
      in contrast with the non-treated group. The present study revealed that total
      aqueous extract preparation of KIOM-C stimulates an antiviral state in murine
      macrophage cells and in mice leading to inhibition of viral infection and
      protection against lethal challenges. 

PMID- 25942442
TI  - The RCSB PDB "Molecule of the Month": Inspiring a Molecular View of Biology.
AB  - The Research Collaboratory for Structural Bioinformatics (RCSB) Molecule of the
      Month series provides a curated introduction to the 3-D biomolecular structures
      available in the Protein Data Bank archive and the tools that are available at
      the RCSB website for accessing and exploring them. A variety of educational
      materials, such as articles, videos, posters, hands-on activities, lesson plans,
      and curricula, build on this series for use in a variety of educational settings
      as a general introduction to key topics, such as enzyme action, protein
      synthesis, and viruses. The series and associated educational materials are
      freely available at www.rcsb.org. 

PMID- 25942443
TI  - Oral Valganciclovir as a Preemptive Treatment for Cytomegalovirus (CMV) Infection
      in CMV-Seropositive Liver Transplant Recipients.
AB  - OBJECTIVES: Cytomegalovirus (CMV) infections in liver transplant recipients are
      common and result in significant morbidity and mortality. Intravenous ganciclovir
      or oral valganciclovir are the standard treatment for CMV infection. The present
      study investigates the efficacy of oral valganciclovir in CMV infection as a
      preemptive treatment after liver transplantation. METHODS: Between 2012 and 2013,
      161 patients underwent liver transplantation at Samsung Medical Center. All
      patients received tacrolimus, steroids, and mycophenolate mofetil. Patients with
      CMV infection were administered oral valganciclovir (VGCV) 900mg/day daily or
      intravenous ganciclovir (GCV) 5mg/kg twice daily as preemptive treatment. Stable
      liver transplant recipients received VGCV. RESULTS: Eighty-three patients (51.6%)
      received antiviral therapy as a preemptive treatment because of CMV infection.
      The model for end-stage liver disease (MELD) score and the proportions of Child
      Pugh class C, hepatorenal syndrome, and deceased donor liver transplantation in
      the CMV infection group were higher than in the no CMV infection group. Sixty-one
      patients received GCV and 22 patients received VGCV. The MELD scores in the GCV
      group were higher than in the VGCV group, but there were no statistical
      differences in the pretransplant variables between the two groups. AST, ALT, and
      total bilirubin levels in the GCV group were higher than in the VGCV group when
      CMV infection occurred. The incidences of recurrent CMV infection in the GCV and
      VGCV groups were 14.8% and 4.5%, respectively (P=0.277). CONCLUSION: Oral
      valganciclovir is feasible as a preemptive treatment for CMV infection in liver
      transplant recipients with stable graft function.

PMID- 25942445
TI  - Genetic Map Construction and Detection of Genetic Loci Underlying Segregation
      Distortion in an Intraspecific Cross of Populus deltoides.
AB  - Based on a two-way pseudo-testcross strategy, high density and complete coverage
      linkage maps were constructed for the maternal and paternal parents of an
      intraspecific F2 pedigree of Populus deltoides. A total of 1,107 testcross
      markers were obtained, and the mapping population consisted of 376 progeny. Among
      these markers, 597 were from the mother, and were assigned into 19 linkage
      groups, spanning a total genetic distance of 1,940.3 cM. The remaining 519
      markers were from the father, and were also were mapped into 19 linkage groups,
      covering 2,496.3 cM. The genome coverage of both maps was estimated as greater
      than 99.9% at 20 cM per marker, and the numbers of linkage groups of both maps
      were in accordance with the 19 haploid chromosomes in Populus. Marker segregation
      distortion was observed in large contiguous blocks on some of the linkage groups.
      Subsequently, we mapped the segregation distortion loci in this mapping pedigree.
      Altogether, eight segregation distortion loci with significant logarithm of odds
      supports were detected. Segregation distortion indicated the uneven transmission
      of the alternate alleles from the mapping parents. The corresponding genome
      regions might contain deleterious genes or be associated with hybridization
      incompatibility. In addition to the detection of segregation distortion loci, the
      established genetic maps will serve as a basic resource for mapping genetic loci
      controlling traits of interest in future studies. 

PMID- 25942444
TI  - Parathyroid Hormone Induces Bone Cell Motility and Loss of Mature Osteocyte
      Phenotype through L-Calcium Channel Dependent and Independent Mechanisms.
AB  - Parathyroid Hormone (PTH) can exert both anabolic and catabolic effects on the
      skeleton, potentially through expression of the PTH type1 receptor (PTH1R), which
      is highly expressed in osteocytes. To determine the cellular and molecular
      mechanisms responsible, we examined the effects of PTH on osteoblast to osteocyte
      differentiation using primary osteocytes and the IDG-SW3 murine cell line, which
      differentiate from osteoblast to osteocyte-like cells in vitro and express GFP
      under control of the dentin matrix 1 (Dmp1) promoter. PTH treatment resulted in
      an increase in some osteoblast and early osteocyte markers and a decrease in
      mature osteocyte marker expression. The gene expression profile of PTH-treated
      Day 28 IDG-SW3 cells was similar to PTH treated primary osteocytes. PTH treatment
      induced striking changes in the morphology of the Dmp1-GFP positive cells in IDG
      SW3 cultures and primary cells from Dmp1-GFP transgenic mice. The cells changed
      from a more dendritic to an elongated morphology and showed increased cell
      motility. E11/gp38 has been shown to be important for cell migration, however,
      deletion of the E11/gp38/podoplanin gene had no effect on PTH-induced motility.
      The effects of PTH on motility were reproduced using cAMP, but not with protein
      kinase A (PKA), exchange proteins activated by cAMP (Epac), protein kinase C
      (PKC) or phosphatidylinositol-4,5-bisphosphonate 3-kinase (Pi3K) agonists nor
      were they blocked by their antagonists. However, the effects of PTH were mediated
      through calcium signaling, specifically through L-type channels normally
      expressed in osteoblasts but decreased in osteocytes. PTH was shown to increase
      expression of this channel, but decrease the T-type channel that is normally more
      highly expressed in osteocytes. Inhibition of L-type calcium channel activity
      attenuated the effects of PTH on cell morphology and motility but did not prevent
      the downregulation of mature osteocyte marker expression. Taken together, these
      results show that PTH induces loss of the mature osteocyte phenotype and promotes
      the motility of these cells. These two effects are mediated through different
      mechanisms. The loss of phenotype effect is independent and the cell motility
      effect is dependent on calcium signaling. 

PMID- 25942447
TI  - Dithiafulvalene functionalized diketopyrrolopyrrole based sensitizers for
      efficient hydrogen production.
AB  - We have designed and synthesized two new diketopyrrolopyrrole (DPP) based organic
      sensitizers (DPPCA and DPPCN) with the dithiafulvalene (DTF) unit as donor and
      cyanoacrylic acid/malononitrile as acceptor moieties. These dyes showed excellent
      efficiency of photocatalytic hydrogen production over a Pt-TiO2 composite via
      solar-induced water splitting. The sensitizers showed broad absorptions over the
      wide visible regime (500-800 nm). In DPPCN, the malononitrile moiety led to
      strong intra-molecular charge transfer, as evidenced by red shifted (~24 nm)
      absorption maxima with highly enhanced molar absorptivity (108 190 M(-1) cm(-1)).
      The electrochemical characterization of as-prepared sensitizers confirmed the
      feasible electron injection from the dye to the TiO2 conduction band (CB) which
      has been further validated by theoretical studies. In this study, the rate of the
      photocatalytic activity was found to be dependent on the acceptor part of the dye
      molecule as DPPCN sensitized Pt-TiO2 (DNPT) exhibited remarkable (1208 MUmol)
      hydrogen evolution yield in comparison to DPPCA sensitized Pt-TiO2 (DAPT) (840
      MUmol). The rigid DPP core made the sensitizers significantly photo-stable as
      affirmed by their high hydrogen production efficiency over 80 h of prolonged
      irradiation. As predicted from density functional theory (DFT) calculations,
      ground state geometry of the dyes was almost planar, facilitating continuous
      conjugation throughout the molecule. Time-dependent DFT (TD-DFT) calculations
      were also carried out to make clear the understanding of charge transfer
      transition of the dye molecules.

PMID- 25942446
TI  - Gender, Age, and Education Level Modify the Association between Body Mass Index
      and Physical Activity: A Cross-Sectional Study in Hangzhou, China.
AB  - INTRODUCTION: Numerous studies have reported a strong inverse association between
      BMI and physical activity in western populations. Recently, the association
      between BMI and physical activity has been considered bidirectional. This study
      aimed to examine the associations of body mass index (BMI) with physical activity
      and sedentary behavior and to explore whether those associations were modified by
      socio-demographic characteristics. MATERIALS AND METHODS: We conducted a
      multistage random sampling survey in three districts of Hangzhou, China, in 2012.
      The International Physical Activity Questionnaire long form was used to collect
      data regarding physical activity and sedentary behavior. A multilevel mixed
      effects regression model was used to assess the associations of BMI with physical
      activity and sedentary behavior. RESULTS: A total of 1362 eligible people (624
      men and 738 women, ages 23-59 years) completed the survey. People who are young
      or middle-aged and have the highest education level are the most inactive.
      Significant differences in the associations between physical activity and BMI
      across socio-demographic groups were identified (sex*BMI, P=0.018; age*BMI,
      P<0.001; education level*BMI, P=0.030). Women or individuals older than 50 had a
      higher level of physical activity with increasing BMI. There was no statistically
      significant association between BMI and sedentary behavior (P=0.450).
      CONCLUSIONS: The associations between BMI and physical activity were modified by
      sex, age, and education level in Hangzhou, China.

PMID- 25942448
TI  - Letter to the Editor: Is There a Retrospective Random Control Study?

PMID- 25942449
TI  - The Moderating Role of Autonomous Motivation on the Relationship between
      Subjective Well-Being and Physical Health.
AB  - The purpose of this study was to investigate the moderator effects of autonomous
      motivation on the relationship between subjective well-being and physical health.
      Using a cluster sampling approach 486 students (403 female and 83 male students)
      were included in this study. Subjective well-being, physical health and
      autonomous motivation were determined by self-report measures. Data were analysed
      using hierarchical regression analysis and analysis of variance. The results show
      that high self-determination moderates the relationship between high subjective
      well-being and physical health. Accordingly, the best physical health was
      reported by participants who had high level of subjective well-being and whose
      behaviours were self-determined. Additional analyses have shown that the
      moderating effect of self-determination is based on the moderational impact of
      autonomous motives and not the controlling ones. Additionally, whether autonomous
      motivation moderates the relationship between components of subjective well-being
      and physical health was also tested. The findings have shown that autonomous
      motives moderate relationship between physical health and one component of well
      being, positive affect. Consequently, a good physical health was found among
      participants with high positive affect and behaviours regulated by high degree of
      autonomous motives. Conclusion which can be drawn from these findings is that if
      an individual behaves autonomously then it can contribute to positive mind-body
      influences and support their own health. 

PMID- 25942450
TI  - The Primary Resistance of Helicobacter pylori in Taiwan after the National Policy
      to Restrict Antibiotic Consumption and Its Relation to Virulence Factors-A
      Nationwide Study.
AB  - OBJECTIVE: The Taiwan Government issued a policy to restrict antimicrobial usage
      since 2001. We aimed to assess the changes in the antibiotic consumption and the
      primary resistance of H. pylori after this policy and the impact of virulence
      factors on resistance. METHODS: The defined daily dose (DDD) of antibiotics was
      analyzed using the Taiwan National Health Insurance (NHI) research database. H.
      pylori strains isolated from treatment naive (N=1395) and failure from prior
      eradication therapies (N=360) from 9 hospitals between 2000 and 2012 were used
      for analysis. The minimum inhibitory concentration was determined by agar
      dilution test. Genotyping for CagA and VacA was determined by PCR method.
      RESULTS: The DDD per 1000 persons per day of macrolides reduced from 1.12 in 1997
      to 0.19 in 2008, whereas that of fluoroquinolones increased from 0.12 in 1997 to
      0.35 in 2008. The primary resistance of amoxicillin, clarithromycin,
      metronidazole, and tetracycline remained as low as 2.2%, 7.9%, 23.7%, and 1.9%
      respectively. However, the primary levofloxacin resistance rose from 4.9% in 2000
      2007 to 8.3% in 2008-2010 and 13.4% in 2011-2012 (p=0.001). The primary
      resistance of metronidazole was higher in females than males (33.1% vs. 18.8%,
      p<0.001), which was probably attributed to the higher consumption of
      nitroimidazole. Neither CagA nor VacA was associated with antibiotic resistance.
      CONCLUSIONS: The low primary clarithromycin and metronidazole resistance of H.
      pylori in Taiwan might be attributed to the reduced consumption of macrolides and
      nitroimidazole after the national policy to restrict antimicrobial usage. Yet,
      further strategies are needed to restrict the consumption of fluoroquinolones in
      the face of rising levofloxacin resistance.

PMID- 25942451
TI  - The NSD family of protein methyltransferases in human cancer.
AB  - The NSD family of protein lysine methyltransferases consists of NSD1,
      NSD2/WHSC1/MMSET and NSD3/WHSC1L1. NSD2 haploinsufficiency causes Wolf-Hirschhorn
      syndrome, while NSD1 mutations lead to the Sotos syndrome. Recently, a number of
      studies showed that the NSD methyltransferases were overexpressed, amplified or
      somatically mutated in multiple types of cancer, suggesting their critical role
      in cancer. These enzymes methylate specific lysine residues on histone tails and
      their dysfunction results in epigenomic aberrations which play a fundamental role
      in oncogenesis. Furthermore, NSD1 was also reported to methylate a nonhistone
      protein substrate, RELA/p65 subunit of NF-kappaB, implying its regulatory
      function through nonhistone methylation pathways. In this review, we summarize
      the current research regarding the role of the NSD family proteins in cancer and
      underline their potential as targets for novel cancer therapeutics. 

PMID- 25942452
TI  - Pressure-stabilized superconductive yttrium hydrides.
AB  - The search for high-temperature superconductors has been focused on compounds
      containing a large fraction of hydrogen, such as SiH4(H2)2, CaH6 and KH6. Through
      a systematic investigation of yttrium hydrides at different hydrogen contents
      using an structure prediction method based on the particle swarm optimization
      algorithm, we have predicted two new yttrium hydrides (YH4 andYH6), which are
      stable above 110 GPa. Three types of hydrogen species with increased H contents
      were found, monatomic H in YH3, monatomic H+molecular "H2" in YH4 and hexagonal
      "H6" unit in YH6. Interestingly, H atoms in YH6 form sodalite-like cage
      sublattice with centered Y atom. Electron-phonon calculations revealed the
      superconductive potential of YH4 and YH6 with estimated transition temperatures
      (Tc) of 84-95 K and 251-264 K at 120 GPa, respectively. These values are higher
      than the predicted maximal Tc of 40 K in YH3. 

PMID- 25942453
TI  - Reverse-correlation analysis of navigation dynamics in Drosophila larva using
      optogenetics.
AB  - Neural circuits for behavior transform sensory inputs into motor outputs in
      patterns with strategic value. Determining how neurons along a sensorimotor
      circuit contribute to this transformation is central to understanding behavior.
      To do this, a quantitative framework to describe behavioral dynamics is needed.
      In this study, we built a high-throughput optogenetic system for Drosophila larva
      to quantify the sensorimotor transformations underlying navigational behavior. We
      express CsChrimson, a red-shifted variant of channelrhodopsin, in specific
      chemosensory neurons and expose large numbers of freely moving animals to random
      optogenetic activation patterns. We quantify their behavioral responses and use
      reverse-correlation analysis to uncover the linear and static nonlinear
      components of navigation dynamics as functions of optogenetic activation patterns
      of specific sensory neurons. We find that linear-nonlinear models accurately
      predict navigational decision-making for different optogenetic activation
      waveforms. We use our method to establish the valence and dynamics of navigation
      driven by optogenetic activation of different combinations of bitter-sensing
      gustatory neurons. Our method captures the dynamics of optogenetically induced
      behavior in compact, quantitative transformations that can be used to
      characterize circuits for sensorimotor processing and their contribution to
      navigational decision making. 

PMID- 25942454
TI  - Chromosome mis-segregation and cytokinesis failure in trisomic human cells.
AB  - Cancer cells display aneuploid karyotypes and typically mis-segregate chromosomes
      at high rates, a phenotype referred to as chromosomal instability (CIN). To test
      the effects of aneuploidy on chromosome segregation and other mitotic phenotypes
      we used the colorectal cancer cell line DLD1 (2n = 46) and two variants with
      trisomy 7 or 13 (DLD1+7 and DLD1+13), as well as euploid and trisomy 13
      amniocytes (AF and AF+13). We found that trisomic cells displayed higher rates of
      chromosome mis-segregation compared to their euploid counterparts. Furthermore,
      cells with trisomy 13 displayed a distinctive cytokinesis failure phenotype. We
      showed that up-regulation of SPG20 expression, brought about by trisomy 13 in
      DLD1+13 and AF+13 cells, is sufficient for the cytokinesis failure phenotype.
      Overall, our study shows that aneuploidy can induce chromosome mis-segregation.
      Moreover, we identified a trisomy 13-specific mitotic phenotype that is driven by
      up-regulation of a gene encoded on the aneuploid chromosome. 

PMID- 25942455
TI  - Recurrent turnover of senescent cells during regeneration of a complex structure.
AB  - Cellular senescence has been recently linked to the promotion of age-related
      pathologies, including a decline in regenerative capacity. While such capacity
      deteriorates with age in mammals, it remains intact in species such as
      salamanders, which have an extensive repertoire of regeneration and can undergo
      multiple episodes through their lifespan. Here we show that, surprisingly, there
      is a significant induction of cellular senescence during salamander limb
      regeneration, but that rapid and effective mechanisms of senescent cell clearance
      operate in normal and regenerating tissues. Furthermore, the number of senescent
      cells does not increase upon repetitive amputation or ageing, in contrast to
      mammals. Finally, we identify the macrophage as a critical player in this
      efficient senescent cell clearance mechanism. We propose that effective
      immunosurveillance of senescent cells in salamanders supports their ability to
      undergo regeneration throughout their lifespan. 

PMID- 25942456
TI  - Altered Monoamine and Acylcarnitine Metabolites in HIV-Positive and HIV-Negative
      Subjects With Depression.
AB  - BACKGROUND: Depression is a frequent comorbidity in HIV infection that has been
      associated with worse treatment outcomes and increased mortality. Recent studies
      suggest that increased innate immune activation and tryptophan catabolism are
      associated with higher risk of depression in HIV infection and other chronic
      inflammatory diseases, but the mechanisms leading to depression remain poorly
      understood. METHODS: The severity of depressive symptoms was assessed by Beck
      Depression Inventory or Center for Epidemiological Studies Depression Scale.
      Untargeted metabolomic profiling of plasma from 104 subjects (68 HIV-positive and
      36 HIV-negative) across 3 independent cohorts was performed using liquid or gas
      chromatography followed by mass spectrometry. Cytokine profiling was by Bioplex
      array. Bioinformatic analysis was performed in Metaboanalyst and R. RESULTS:
      Decreased monoamine metabolites (phenylacetate, 4-hydroxyphenylacetate) and
      acylcarnitines (propionylcarnitine, isobutyrylcarnitine, isovalerylcarnitine, 2
      methylbutyrylcarnitine) in plasma distinguished depressed subjects from controls
      in HIV-positive and HIV-negative cohorts, and these alterations correlated with
      the severity of depressive symptoms. In HIV-positive subjects, acylcarnitines and
      other markers of mitochondrial function correlated inversely with tryptophan
      catabolism, a marker of interferon responses, suggesting interrelationships
      between inflammatory pathways, tryptophan catabolism, and metabolic alterations
      associated with depression. Altered metabolites mapped to pathways involved in
      monoamine metabolism, mitochondrial function, and inflammation, suggesting a
      model in which complex relationships between monoamine metabolism and
      mitochondrial bioenergetics contribute to biological mechanisms involved in
      depression that may be augmented by inflammation during HIV infection.
      CONCLUSIONS: Integrated approaches targeting inflammation, monoamine metabolism,
      and mitochondrial pathways may be important for prevention and treatment of
      depression in people with and without HIV.

PMID- 25942458
TI  - Pharmacokinetic Drug-Drug Interaction Study Between Raltegravir and Atorvastatin
      20 mg in Healthy Volunteers.
AB  - BACKGROUND: Dyslipidemia is highly prevalent among patients with HIV infection
      and contributes to an increased risk of cardiovascular disease. We investigated
      the influence of a frequently used statin, atorvastatin, on the pharmacokinetics
      of the HIV-integrase inhibitor raltegravir and vice versa. METHODS: Open-label,
      crossover 3-period phase I trial in 24 healthy volunteers. Subjects took
      raltegravir 400 mg two times a day for 7 days, atorvastatin 20 mg once a day for
      7 days, and the combination of atorvastatin 20 mg once a day + raltegravir 400 mg
      two times a day for 7 days with 2-week washout periods in between. Intensive
      steady-state 12- and 24-hour pharmacokinetic blood sampling was performed.
      Geometric mean ratios of the test treatment (combination raltegravir +
      atorvastatin) versus the reference treatment (raltegravir or atorvastatin alone)
      and 90% confidence intervals were calculated for the area under the plasma
      concentration-time curve (AUC). Fasting lipid profiles were obtained to assess
      short-term lipid-lowering effect of atorvastatin with or without concomitant
      raltegravir use. RESULTS: Twenty-four healthy volunteers (11 males) were
      enrolled. All but 1 subject completed the trial, and no serious adverse events
      were reported. Geometric mean ratios (90% confidence interval) were 1.01 (0.68
      1.51) for raltegravir AUC(0-12h) and 1.00 (0.90-1.11) for atorvastatin AUC(0
      24h). The AUC(0-24h) metabolite-to-parent ratio for atorvastatin lactone, ortho
      hydroxy, and para-hydroxy atorvastatin did not change during concomitant
      raltegravir use. The effect of atorvastatin on low-density lipoprotein
      cholesterol was not significantly different when combined with raltegravir versus
      atorvastatin alone (P = 0.638). CONCLUSIONS: Atorvastatin 20 mg has no clinically
      relevant effect on the pharmacokinetics of raltegravir and vice versa. The
      combination was well tolerated and can be administered without dose adjustments.

PMID- 25942457
TI  - Sexual Relationships Outside Primary Partnerships and Abstinence Are Associated
      With Lower Adherence and Adherence Gaps: Data From the Partners PrEP Ancillary
      Adherence Study.
AB  - OBJECTIVE: To assess the role of sexual relationships on levels and patterns of
      adherence to medication for pre-exposure prophylaxis against HIV. METHODS: We
      enrolled 1147 HIV-negative individuals in long-term serodiscordant relationships
      at 3 sites in Uganda from the Partners Pre-exposure Prophylaxis Study, a
      randomized placebo-controlled trial of daily oral tenofovir and
      emtricitabine/tenofovir. We used generalized estimation equations to assess the
      effects of sexual relationships on low adherence (<80%) and on gaps in adherence.
      RESULTS: Fifty-three percent were male, 51% were 18-34 years and 24% were
      polygamous. Participants who reported sex in the past month with someone other
      than their primary partner and with <100% condom use were more than twice as
      likely to have low adherence [adjusted odds ratio (aOR) = 2.48, 95% CI: 1.70 to
      3.62] compared with those who had sex with only their primary partners and 100%
      condom use. Using the same reference group, those who abstained from sex in the
      previous month had 30% increased odds of low adherence (aOR = 1.30, 95% CI: 1.05
      to 1.62) and participants in nonpolygamous marriages who reported sex with both
      their primary and other partners and <100% condom use were almost twice as likely
      to be low adherers (aOR = 1.76, 95% CI: 1.01 to 3.08). At least one 72-hour gap
      in adherence was seen in 598 participants (54.7%); 23.2% had at least one 1-week
      gap. CONCLUSIONS: Risk of low overall adherence was higher in participants who
      reported sex outside primary partnerships and suboptimal condom use, as well as
      in those who abstained from sex. Adherence gaps were common, potentially creating
      risk for HIV acquisition.

PMID- 25942459
TI  - Immune Reconstitution but Persistent Activation After 48 Weeks of Antiretroviral
      Therapy in Youth With Pre-Therapy CD4 >350 in ATN 061.
AB  - BACKGROUND: Measures of immune outcomes in youth who initiate combination
      antiretroviral therapy (cART) early in HIV infection are limited. DESIGN:
      Adolescent Trials Network 061 examined changes over 48 weeks of cART in T-cell
      subsets and markers of T-cell and macrophage activation in subjects with pre
      therapy CD4 > 350 cells/mm. All subjects had optimal viral suppression from weeks
      24 through 48. METHODS: Subjects (n = 48) initiated cART with
      tenofovir/emtricitabine plus ritonavir-boosted atazanavir. Data were collected at
      baseline and weeks 12, 24, and 48. Trends were compared to uninfected controls.
      RESULTS: Significant increases over 48 weeks were noted in all CD4 populations,
      including total, naive, central memory (CM), and effector memory RO (EM RO) and
      effector memory RA (EM RA), whereas numbers of CM and EM RO CD8 cells declined
      significantly. By week 48, CD4 naive cells were similar to controls, whereas CM
      CD4 cells remained significantly lower and EM RO and EM RA subsets were
      significantly higher. CD38 and HLA DR expression, both individually and when co
      expressed, decreased over 48 weeks of cART on CD8 cells but remained
      significantly higher than controls at week 48. In contrast, markers of macrophage
      activation measured by sCD14 and sCD163 in plasma did not change with cART and
      were significantly higher than controls. CONCLUSIONS: In youth initiating early
      cART, CD4 cell reconstitution is robust with decreases in CD8 cells. However, CD8
      T-cell and macrophage activation persists at higher levels than uninfected
      controls.

PMID- 25942460
TI  - HIV Infection Is Associated With Increased Risk for Acute Exacerbation of COPD.
AB  - BACKGROUND: Poorly controlled HIV infection is associated with increased risk for
      chronic obstructive pulmonary disease (COPD). Acute exacerbations of COPD
      (AECOPD) are major contributors to morbidity and mortality. Little is known about
      the association between HIV infection and AECOPD. METHODS: We identified 167
      individuals with spirometry-confirmed COPD from a longitudinal study of current
      or former injection drug users at risk or with HIV infection. AECOPD, defined as
      self-report of worsening breathing requiring treatment with antibiotics or
      steroids, was assessed at 6-month study visits. Multivariable logistic regression
      identified factors associated with AECOPD. RESULTS: Of 167 participants, the mean
      age was 52 years; 89% were black, 30% female, and 32% HIV infected (median CD4
      count: 312 cells per milliliter, 46% with detectable HIV RNA). After adjusting
      for age, gender, smoking history, comorbidity treatment, and airflow obstruction
      severity, HIV was independently associated with a 2.47 increased odds of AECOPD
      [95% confidence interval (CI): 1.22 to 5.00]. Compared with HIV-uninfected
      persons, HIV-infected persons with undetectable (<50 copies/mL) HIV RNA levels
      and those with a CD4 count >=350 cells per cubic millimeter demonstrated
      increased AECOPD (odds ratio, 2.91; 95% CI: 1.26 to 6.71; odds ratio, 4.16; 95%
      CI: 1.87 to 9.27, respectively). Higher AECOPD risk was observed with higher CD4
      counts irrespective of treatment for comorbid diseases. CONCLUSIONS: HIV
      infection is independently associated with increased odds of AECOPD, potentially
      due to differences in treatment access and to variable disease manifestation by
      immune status. Providers should be aware that HIV infection may increase risk for
      AECOPD and that symptom may be more discernible with intact immune function.

PMID- 25942461
TI  - Retention of Adult Patients on Antiretroviral Therapy in Low- and Middle-Income
      Countries: Systematic Review and Meta-analysis 2008-2013.
AB  - BACKGROUND: We previously published systematic reviews of retention in care after
      antiretroviral therapy initiation among general adult populations in sub-Saharan
      Africa. We estimated 36-month retention at 73% for publications from 2007 to
      2010. This report extends the review to cover 2008-2013 and expands it to all low
      and middle-income countries. METHODS: We searched PubMed, Embase, Cochrane
      Register, and ISI Web of Science from January 1, 2008, to December 31, 2013, and
      abstracts from AIDS and IAS from 2008-2013. We estimated retention across cohorts
      using simple averages and interpolated missing times through the last time
      reported. We estimated all-cause attrition (death, loss to follow-up) for
      patients receiving first-line antiretroviral therapy in routine settings in low-
      and middle-income countries. RESULTS: We found 123 articles and abstracts
      reporting retention for 154 patient cohorts and 1,554,773 patients in 42
      countries. Overall, 43% of all patients not retained were known to have died.
      Unweighted averages of reported retention were 78%, 71%, and 69% at 12, 24, and
      36 months, after treatment initiation, respectively. We estimated 36-month
      retention at 65% in Africa, 80% in Asia, and 64% in Latin America and the
      Caribbean. From lifetable analysis, we estimated retention at 12, 24, 36, 48, and
      60 months at 83%, 74%, 68%, 64%, and 60%, respectively. CONCLUSIONS: Retention at
      36 months on treatment averages 65%-70%. There are several important gaps in the
      evidence base, which could be filled by further research, especially in terms of
      geographic coverage and duration of follow-up.

PMID- 25942462
TI  - Super Learner Analysis of Electronic Adherence Data Improves Viral Prediction and
      May Provide Strategies for Selective HIV RNA Monitoring.
AB  - OBJECTIVE: Regular HIV RNA testing for all HIV-positive patients on
      antiretroviral therapy (ART) is expensive and has low yield since most tests are
      undetectable. Selective testing of those at higher risk of failure may improve
      efficiency. We investigated whether a novel analysis of adherence data could
      correctly classify virological failure and potentially inform a selective testing
      strategy. DESIGN: Multisite prospective cohort consortium. METHODS: We evaluated
      longitudinal data on 1478 adult patients treated with ART and monitored using the
      Medication Event Monitoring System (MEMS) in 16 US cohorts contributing to the
      MACH14 consortium. Because the relationship between adherence and virological
      failure is complex and heterogeneous, we applied a machine-learning algorithm
      (Super Learner) to build a model for classifying failure and evaluated its
      performance using cross-validation. RESULTS: Application of the Super Learner
      algorithm to MEMS data, combined with data on CD4 T-cell counts and ART regimen,
      significantly improved classification of virological failure over a single MEMS
      adherence measure. Area under the receiver operating characteristic curve,
      evaluated on data not used in model fitting, was 0.78 (95% confidence interval:
      0.75 to 0.80) and 0.79 (95% confidence interval: 0.76 to 0.81) for failure
      defined as single HIV RNA level >1000 copies per milliliter or >400 copies per
      milliliter, respectively. Our results suggest that 25%-31% of viral load tests
      could be avoided while maintaining sensitivity for failure detection at or above
      95%, for a cost savings of $16-$29 per person-month. CONCLUSIONS: Our findings
      provide initial proof of concept for the potential use of electronic medication
      adherence data to reduce costs through behavior-driven HIV RNA testing.

PMID- 25942463
TI  - Targeting pre-exposure prophylaxis among men who have sex with men in the United
      States and Peru: partnership types, contact rates, and sexual role.
AB  - BACKGROUND: We aim to identify optimal strategies for deploying pre-exposure
      prophylaxis among men who have sex with men (MSM) in the United States and Peru
      to maximize population-level effectiveness in an efficient manner. We use
      epidemic models to simulate the impact of targeting strategies. Most studies have
      focused on targeting either the general population or high-risk MSM. Alternative
      strategies, including serodiscordant couples, may better balance effectiveness
      and efficiency. METHODS: We use dynamic stochastic sexual network models based on
      exponential-family random graph modeling, parameterized from behavioral surveys
      of MSM in the United States and Peru. These models represent main partnerships
      and casual contacts separately, permitting modeling of interventions targeting
      men whose risk derives from combinations of relational types. We also model
      varying rates of uptake and adherence to pre-exposure prophylaxis (PrEP). We
      assess sensitivity of results to risk compensation through increases in
      condomless casual contacts and condomless sex in main partnerships. RESULTS:
      Targeting all men who are not exclusively insertive has the largest impact on HIV
      incidence, but targeting only those with high levels of casual activity yields
      comparable results using fewer person-years on PrEP. The effect is robust to risk
      compensation in the United States, but less so in Peru. Targeting serodiscordant
      main partnerships does not significantly impact incidence, but requires fewer
      person-years on PrEP per infection averted than other strategies. CONCLUSIONS:
      PrEP could be effective in reducing new infections at the population level in
      both settings. Serodiscordant partnerships are an attractive component of a
      targeting program, but targeting should include other high-risk men.

PMID- 25942464
TI  - Brief Report: Health-Seeking Behavior and Symptoms Associated With Early HIV
      Infection: Results From a Population-Based Cohort in Southern Malawi.
AB  - HIV transmission is most likely to occur during the first few months after
      infection, yet few cases are identified during this period. Using a population
      based cohort of young Malawian women, we identify the distinct symptomology and
      health-seeking behavior marking early HIV infection by comparing it with periods
      of seronegativity and chronic infection. During early HIV infection, women are
      more likely to report malaria-like symptoms and visit clinics for malaria care.
      In malaria-endemic contexts, where acute HIV symptoms are commonly mistaken for
      malaria, early diagnostic HIV testing and counseling should be integrated into
      health care settings where people commonly seek treatment for malaria. 

PMID- 25942465
TI  - Implementation and Operational Research: Evaluation of Swaziland's Hub-and-Spoke
      Model for Decentralizing Access to Antiretroviral Therapy Services.
AB  - BACKGROUND: In 2007, Swaziland initiated a hub-and-spoke model for decentralizing
      antiretroviral therapy (ART) access. Decentralization was facilitated through (1)
      down-referral of stable ART patients from overburdened central facilities (hubs)
      to primary health care clinics (spokes) and (2) ART initiation at spokes (spoke
      initiation). METHODS: We conducted a nationally representative retrospective
      cohort study among adult ART enrollees during 2004-2010 to assess the effect of
      down-referral and spoke-initiation on rates of loss to follow-up (LTFU), death,
      and attrition (death or LTFU). Sixteen of 31 hubs were randomly selected using
      probability-proportional-to-size sampling. Seven selected facilities had
      initiated the hub-and-spoke model by study start. At these facilities, 1149 of
      24,782 hub-initiated and maintained and 878 of 7722 down-referred or spoke
      initiated patient records were randomly selected and analyzed. At the 9 hub-only
      facilities, 483 of 6638 records were randomly selected and analyzed.
      Multivariable proportional hazards regression was used to assess effect of down
      referral (a time-varying covariate) and spoke-initiation on outcomes. RESULTS: At
      ART initiation, median age was 35, 65% were female, and median CD4 count was 147
      cells per microliter. Controlling for known confounders, down-referral was
      strongly protective against LTFU [adjusted hazard ratio (AHR) 0.38; 95%
      confidence interval (CI): 0.29 to 0.50] and attrition (AHR = 0.50; 95% CI: 0.34
      to 0.76) but not mortality. Compared with hub-initiated and maintained patients,
      spoke-initiated patients had lower LTFU (AHR 0.59; 95% CI: 0.45 to 0.77) and
      attrition rates (AHR 0.60; 95% CI: 0.47 to 0.77), but not mortality. CONCLUSIONS:
      Down-referral and spoke-initiation within a hub-and-spoke ART decentralization
      model were protective against LTFU and overall attrition and could facilitate
      future ART program expansion.

PMID- 25942466
TI  - Implementation and Operational Research: Evaluation of Loss-to-Follow-up and
      Postoperative Adverse Events in a Voluntary Medical Male Circumcision Program in
      Nyanza Province, Kenya.
AB  - BACKGROUND: More than 4.7 million voluntary medical male circumcisions (VMMCs)
      had been provided by HIV prevention programs in sub-Saharan Africa through 2013.
      All VMMC clients are recommended to return to the clinic for postoperative follow
      up, although adherence is variable. The clinical status of clients who do not
      return is largely unknown. METHODS: VMMC clients from Nyanza Province, Kenya,
      aged older than or equal to 13 years, were recruited immediately after surgery
      from April to October 2012 from high-volume sites. Medical record reviews at 13
      14 days after surgery indicated which clients had been adherent with recommended
      follow-up (ADFU) and which were lost-to-follow-up (LTFU). Clients in the LTFU
      group received clinical evaluations at home approximately 2 weeks postsurgery.
      Adverse events (AEs) and AE rates were compared between the ADFU and LTFU groups.
      RESULTS: Of 4504 males approached in 50 VMMC sites, 1699 (37.7%) were eligible
      and enrolled and 1600 of 1699 (94.2%) contributed to follow-up and AE data.
      Medical record review indicated 897 of 1600 (56.1%) were LTFU, and 762 (84.9%) of
      these received home-based clinical evaluations. The rate of moderate or severe AE
      diagnosis was 6.8% in the LTFU group vs. 3.3% in the ADFU group (relative risk =
      2.1, 95% confidence interval: 1.3 to 3.4). CONCLUSIONS: The moderate or severe AE
      diagnosis rate was approximately 2 times higher in the LTFU group. National
      programs should consider instituting surveillance systems to detect AEs that
      might otherwise go unnoticed. Providers should emphasize the importance of follow
      up and actively contact LTFU clients to ensure care is provided throughout the
      entire postoperative course for all.

PMID- 25942467
TI  - Similar Success Rates but Lower Incidence of Telaprevir-Related Rash in HIV/HCV
      Coinfected as Compared to HCV-Monoinfected Patients Treated With Triple Anti-HCV
      Therapy.

PMID- 25942468
TI  - Decreasing Impact of Requiring Assistance Injecting on HIV Incidence.

PMID- 25942470
TI  - Gender, coping strategies, homelessness stressors, and income generation among
      homeless young adults in three cities.
AB  - This study examined gender differences among homeless young adults' coping
      strategies and homelessness stressors as they relate to legal (e.g., full-time
      employment, selling personal possessions, selling blood/plasma) and illegal
      economic activity (e.g., selling drugs, theft, prostitution). A sample of 601
      homeless young adults was recruited from 3 cities (Los Angeles, CA [n = 200],
      Austin, TX [n = 200], and Denver, CO [n = 201]) to participate in semi-structured
      interviews from March 2010 to July 2011. Risk and resilience correlates of legal
      and illegal economic activity were analyzed using six Ordinary Least Squares
      regression models with the full sample and with the female and male sub-samples.
      In the full sample, three variables (i.e., avoidant coping, problem-focused
      coping, and mania) were associated with legal income generation whereas eight
      variables (i.e., social coping, age, arrest history, transience, peer substance
      use, antisocial personality disorder [ASPD], substance use disorder [SUD], and
      major depressive episode [MDE]) were associated with illegal economic activity.
      In the female sub-sample, three variables (i.e., problem-focused coping,
      race/ethnicity, and transience) were correlated with legal income generation
      whereas six variables (i.e., problem-focused coping, social coping, age, arrest
      history, peer substance use, and ASPD) were correlated with illegal economic
      activity. Among males, the model depicting legal income generation was not
      significant yet seven variables (i.e., social coping, age, transience, peer
      substance use, ASPD, SUD, and MDE) were associated with illegal economic
      activity. Understanding gender differences in coping strategies and economic
      activity might help customize interventions aimed at safe and legal income
      generation for this population. 

PMID- 25942469
TI  - Interferon-Inducible Transmembrane Protein 3 Genetic Variant rs12252 and
      Influenza Susceptibility and Severity: A Meta-Analysis.
AB  - BACKGROUND: The pandemic influenza A (H1N1) pdm09 virus, avian influenza A (H5N1)
      virus, and influenza A (H7N9) virus induced severe morbidity and mortality
      throughout the world. Previous studies suggested a close association between the
      interferon-induced transmembrane protein-3 (IFITM3) genetic variant rs12252 and
      influenza. Here, we explored the correlation between the rs12252 and influenza
      susceptibility and severity using meta-analysis. METHODS: Relevant studies
      published before May 22, 2014 were retrieved from PubMed, ISI web of knowledge,
      EBSCO, and Cochrane central register of controlled trials databases. Association
      between rs12252 and influenza susceptibility and severity were determined using
      statistical analysis of odds ratios (ORs). RESULTS: A total of four studies
      consisting of 445 cases and 4180 controls were included in our analysis.
      Generally, there is increased risk of influenza in subjects carrying rs12252 in
      the recessive model (CC vs. CT+TT: OR = 2.35, 95% CI: 1.49-3.70, P<0.001), the
      dominant model (CC+CT vs. TT: OR=1.60, 95% CI: 1.18-2.22, P=0.003), the
      homozygote comparison (CC vs. TT: OR=4.11, 95% CI: 2.15-7.84, P<0.001), and the
      allele contrast (C vs. T: OR=1.67, 95% CI: 1.32-2.13, P<0.001). Stratification
      analysis of ethnicity and severity revealed a significant increase in influenza
      susceptibility by IFITM3-SNP rs12252 among both Asian and Caucasian population.
      SNP rs12252 shows significant impact on severe infections (P<0.05), but not on
      mild influenza. Besides, our result also associated rs12252 with influenza
      severity (severe vs. mild: OR=2.37, 95% CI: 1.32-4.25, P=0.004), (severe vs.
      control: OR=2.70, 95% CI: 1.85-3.94, P<0.001). CONCLUSION: Our meta-analysis
      suggests a significant association between a minor IFITM3 allele (SNP rs12252-C)
      with severe influenza susceptibility, but not in mild influenza subjects, in both
      UK Caucasians and Han Chinese population. The rs12252-C allele causes a 23.7%
      higher chance of infection and also constitutes a risk factor for more severe
      influenza.

PMID- 25942471
TI  - P21 deficiency delays regeneration of skeletal muscular tissue.
AB  - The potential relationship between cell cycle checkpoint control and tissue
      regeneration has been indicated. Despite considerable research being focused on
      the relationship between p21 and myogenesis, p21 function in skeletal muscle
      regeneration remains unclear. To clarify this, muscle injury model was recreated
      by intramuscular injection of bupivacaine hydrochloride in the soleus of p21
      knockout (KO) mice and wild type (WT) mice. The mice were sacrificed at 3, 14,
      and 28 days post-operation. The results of hematoxylin-eosin staining and
      immunofluorescence of muscle membrane indicated that muscle regeneration was
      delayed in p21 KO mice. Cyclin D1 mRNA expression and both Ki-67 and PCNA
      immunohistochemistry suggested that p21 deficiency increased cell cycle and
      muscle cell proliferation. F4/80 immunohistochemistry also suggested the increase
      of immune response in p21 KO mice. On the other hand, both the mRNA expression
      and western blot analysis of MyoD, myogenin, and Pax7 indicated that muscular
      differentiation was delayed in p21KO mice. Considering these results, we
      confirmed that muscle injury causes an increase in cell proliferation. However,
      muscle differentiation in p21 KO mice was inhibited due to the low expression of
      muscular synthesis genes, leading to a delay in the muscular regeneration. Thus,
      we conclude that p21 plays an important role in the in vivo healing process in
      muscular injury. 

PMID- 25942473
TI  - Variations in Student Mental Health and Treatment Utilization Across US Colleges
      and Universities.
AB  - OBJECTIVE: On US college campuses, mental health problems are highly prevalent,
      appear to be increasing, and are often untreated. Concerns about student mental
      health are well documented, but little is known about potential variations across
      the diversity of institutions of higher education. PARTICIPANTS: Participants
      were 43,210 undergraduates at 72 campuses that participated in the Healthy Minds
      Study from 2007 to 2013. METHODS: Multivariable logistic regressions focus on
      associations between institutional characteristics and student mental health and
      treatment utilization. RESULTS: The following institutional characteristics are
      associated with worse mental health: doctoral-granting, public, large enrollment,
      nonresidential, less competitive, and lower graduation rates. Among students with
      apparent mental health problems, treatment utilization is higher at doctorate
      granting institutions, baccalaureate colleges, institutions with small
      enrollments, and schools with strong residential systems. CONCLUSIONS: Although
      high rates of mental health problems and low treatment utilization are major
      concerns at all types of institutions of higher education, substantial variation
      occurs across campuses.

PMID- 25942472
TI  - A Phase 1 Randomized, Open Label, Rectal Safety, Acceptability, Pharmacokinetic,
      and Pharmacodynamic Study of Three Formulations of Tenofovir 1% Gel (the CHARM-01
      Study).
AB  - OBJECTIVES: The CHARM-01 study characterized the safety, acceptability,
      pharmacokinetics (PK), and pharmacodynamics (PD) of three tenofovir (TFV) gels
      for rectal application. The vaginal formulation (VF) gel was previously used in
      the CAPRISA 004 and VOICE vaginal microbicide Phase 2B trials and the RMP-02/MTN
      006 Phase 1 rectal safety study. The reduced glycerin VF (RGVF) gel was used in
      the MTN-007 Phase 1 rectal microbicide trial and is currently being evaluated in
      the MTN-017 Phase 2 rectal microbicide trial. A third rectal specific formulation
      (RF) gel was also evaluated in the CHARM-01 study. METHODS: Participants received
      4 mL of the three TFV gels in a blinded, crossover design: seven daily doses of
      RGVF, seven daily doses of RF, and six daily doses of placebo followed by one
      dose of VF, in a randomized sequence. Safety, acceptability, compartmental PK,
      and explant PD were monitored throughout the trial. RESULTS: All three gels were
      found to be safe and acceptable. RF and RGVF PK were not significantly different.
      Median mucosal mononuclear cell (MMC) TFV-DP trended toward higher values for RF
      compared to RGVF (1136 and 320 fmol/106 cells respectively). Use of each gel in
      vivo was associated with significant inhibition of ex vivo colorectal tissue HIV
      infection. There was also a significant negative correlation between the tissue
      levels of TFV, tissue TFV-DP, MMC TFV-DP, rectal fluid TFV, and explant HIV-1
      infection. CONCLUSIONS: All three formulations were found to be safe and
      acceptable. However, the safety profile of the VF gel was only based on exposure
      to one dose whereas participants received seven doses of the RGVF and RF gels.
      There was a trend towards higher tissue MMC levels of TFV-DP associated with use
      of the RF gel. Use of all gels was associated with significant inhibition of ex
      vivo tissue HIV infection. TRIAL REGISTRATION: ClinicalTrials.gov NCT01575405.

PMID- 25942474
TI  - Beetroot juice does not enhance altitude running performance in well-trained
      athletes.
AB  - We hypothesized that acute dietary nitrate (NO3(-)) provided as concentrated
      beetroot juice supplement would improve endurance running performance of well
      trained runners in normobaric hypoxia. Ten male runners (mean (SD): sea level
      maximal oxygen uptake, 66 (7) mL.kg(-1).min(-1); 10 km personal best, 36 (2) min)
      completed incremental exercise to exhaustion at 4000 m and a 10-km treadmill time
      trial at 2500 m simulated altitude on separate days after supplementation with ~7
      mmol NO3(-) and a placebo at 2.5 h before exercise. Oxygen cost, arterial oxygen
      saturation, heart rate, and ratings of perceived exertion (RPE) were determined
      during the incremental exercise test. Differences between treatments were
      determined using means [95% confidence intervals], paired sample t tests, and a
      probability of individual response analysis. NO3(-) supplementation increased
      plasma nitrite concentration (NO3(-), 473 (226) nmol.L(-1) vs. placebo, 61 (37)
      nmol.L(-1), P < 0.001) but did not alter time to exhaustion during the
      incremental test (NO3(-), 402 (80) s vs. placebo 393 (62) s, P = 0.5) or time to
      complete the 10-km time-trial (NO3(-), 2862 (233) s vs. placebo, 2874 (265) s, P
      = 0.6). Further, no practically meaningful beneficial effect on time-trial
      performance was observed as the 11 [-60 to 38] s improvement was less than the a
      priori determined minimum important difference (51 s), and only 3 runners
      experienced a "likely, probable" performance improvement. NO3(-) also did not
      alter oxygen cost, arterial oxygen saturation, heart rate, or RPE. Acute dietary
      NO3(-) supplementation did not consistently enhance running performance of well
      trained athletes in normobaric hypoxia. 

PMID- 25942475
TI  - TTAC-0001, a human monoclonal antibody targeting VEGFR-2/KDR, blocks tumor
      angiogenesis.
AB  - Angiogenesis is one of the most important processes for cancer cell survival,
      tumor growth and metastasis. Vascular endothelial growth factor (VEGF) and its
      receptor, particularly VEGF receptor-2 (VEGFR-2, or kinase insert domain
      containing receptor, KDR), play critical roles in tumor-associated angiogenesis.
      We developed TTAC-0001, a human monoclonal antibody against VEGFR-2/KDR from a
      fully human naive single-chain variable fragment phage library. TTAC-0001 was
      selected as a lead candidate based on its affinity, ligand binding inhibition and
      inhibition of VEGFR-2 signal in human umbilical vein endothelial cells (HUVEC).
      TTAC-0001 inhibited binding of VEGF-C and VEGF-D to VEGFR-2 in addition to VEGF
      A. It binds on the N-terminal regions of domain 2 and domain 3 of VEGFR-2. It
      could inhibit the phosphorylation of VEGFR-2/KDR and ERK induced by VEGF in
      HUVEC. TTAC-0001 also inhibited VEGF-mediated endothelial cell proliferation,
      migration and tube formation in vitro, as well as ex vivo vessel sprouting from
      rat aortic rings and neovascularization in mouse matrigel model in vivo. Our data
      indicates that TTAC-0001 blocks the binding of VEGFs to VEGFR-2/KDR and inhibits
      VEGFR-induced signaling pathways and angiogenesis. Therefore, these data strongly
      support the further development of TTAC-0001 as an anti-cancer agent in the
      clinic. 

PMID- 25942476
TI  - Aberrant TGFbeta Signalling Contributes to Dysregulation of Sphingolipid
      Metabolism in Intrauterine Growth Restriction.
AB  - CONTEXT: Sphingolipids function as key bioactive mediators that regulate cell
      fate events in a variety of systems. Disruptions in sphingolipid metabolism
      characterize several human pathologies. OBJECTIVE: In the present study we
      examined sphingolipid metabolism in intrauterine growth restriction (IUGR), a
      severe disorder complicating 4-7% of pregnancies at increased risk of perinatal
      morbidity and mortality, which is characterized by placental dysfunction and
      augmented trophoblast cell death rates. DESIGN, SETTING, AND PARTICIPANTS:
      Placentae from early severe IUGR with documented abnormal umbilical artery
      Doppler defined as absence or reverse of end diastolic velocity and a birth
      weight below the fifth percentile for gestational age were collected (n = 58).
      Placental tissues obtained from healthy, age-matched preterm and term deliveries
      (n = 46; TC, n=28) were included as controls. RESULTS: Sphingolipid analysis by
      tandem mass spectrometry revealed elevated sphingosine and decreased ceramide
      levels in placentae from pregnancies complicated by IUGR relative to age-matched
      controls. Sphingosine accumulation was due to accelerated ceramide breakdown via
      increased acid ceramidase (ASAH1) expression/activity caused by augmented TGFbeta
      signalling via the ALK5/SMAD2 pathway. In addition, a marked reduction in
      sphingosine kinase 1 (SPHK1) expression/activity due to impaired TGFbeta
      signalling via ALK1/SMAD1 contributed to the sphingosine buildup in IUGR. Of
      clinical significance, ALK/SMAD signalling pathways were differentially altered
      in IUGR placentae. CONCLUSIONS: Altered TGFbeta signalling in IUGR placentae
      causes dysregulation of sphingolipid metabolism, which may contribute to the
      increased trophoblast cell death typical of this pathology.

PMID- 25942477
TI  - Elevated Lipoprotein Lipase Activity Does Not Account for the Association Between
      Adiponectin and HDL in Type 1 Diabetes.
AB  - CONTEXT: Increased high-density lipoprotein cholesterol (HDL-C) is common in type
      1 diabetes (T1D) and is associated both with hyperadiponectinemia and with
      elevated lipoprotein lipase activity (LPL). Because adiponectin has been shown to
      increase LPL expression, elevated LPL may link the hyperadiponectinemia in T1D
      with increased HDL. OBJECTIVE: The purpose of this study was to determine whether
      LPL activity accounts for the association between adiponectin and HDL in T1D.
      DESIGN, PARTICIPANTS, AND SETTING: A cohort of 127 patients with T1D attending
      the Diabetes Clinic at the University of Miami and 103 healthy control subjects
      were recruited. MAIN OUTCOME MEASURE: HDL-C and adiponectin were measured in the
      full cohort and in a subgroup, HDL subfractions were obtained by
      ultracentrifugation, and LPL and hepatic lipase were measured in postheparin
      plasma. RESULTS: Total HDL-C and the lowest density HDL subfraction,
      apolipoprotein A-I, LPL activity, and adiponectin levels were higher in subjects
      with T1D than in control subjects (P < .05). Both adiponectin and LPL activity
      were directly associated with total HDL-C and its lowest density subfraction, but
      adiponectin and LPL were not correlated (P = 0.13). Adiponectin alone explained
      11.6% and adiponectin plus LPL explained 23.8% of the HDL-C variance. In a
      multivariate model, adiponectin remained an independent predictor of HDL-C along
      with LPL and serum creatinine, explaining together 27% of HDL-C variance.
      CONCLUSIONS: Adiponectin was strongly associated with HDL-C in T1D, suggesting
      that hyperadiponectinemia is linked to the elevated HDL-C in this population.
      However, this relationship is independent of the association between LPL and HDL
      C. Thus, elevated adiponectin and LPL activity are independently related to
      increased HDL-C in T1D.

PMID- 25942480
TI  - Circulating Progenitor Cell Count Predicts Microvascular Outcomes in Type 2
      Diabetic Patients.
AB  - CONTEXT: Diabetes reduces the levels of circulating progenitor cells (CPCs) and
      endothelial progenitor cells (EPCs), which promote vascular repair and are
      inversely correlated with cardiovascular risk. OBJECTIVE: The objective of the
      study was to test whether CPC/EPC levels predict onset/progression of
      microangiopathy in a cohort of type 2 diabetic (T2D) patients. DESIGN: This was a
      pseudoprospective study with a 3.9-year follow-up. SETTING: The study was
      conducted at a tertial referral diabetes outpatient clinic. PATIENTS: A total of
      187 T2D patients having a baseline determination of CPCs/EPCs participated in the
      study. INTERVENTION: Baseline data on demographics, anthropometrics, concomitant
      risk factors, diabetic complications, and medications were collected. MAIN
      OUTCOME MEASURE: Onset or progression of microangiopathy was assessed at follow
      up compared with baseline. RESULTS: New onset or progression of microalbuminuria,
      chronic kidney disease, retinopathy, and neuropathy occurred in 70 patients
      (9.5%/y). After controlling the false discovery rate, baseline CD34(+) CPCs and
      EPCs were significantly lower in patients with onset/progression of
      microalbuminuria and any microangiopathy. Patients with baseline CD34(+) CPC or
      CD133(+)/kinase insert domain-containing receptor(+)/EPC levels below the median
      were more likely to experience worsening microangiopathy than those with high
      cell levels. Independently from confounders, including age, sex, glycated
      hemoglobin, and diabetes duration, CD34(+) cells predicted onset/progression of
      microalbuminuria, retinopathy, and any microangiopathy in false discovery rate
      adjusted analyses. A low CD34(+) cell count limited the beneficial effects of
      renin-angiotensin system blockers on microalbuminuria progression. CONCLUSIONS:
      Levels of circulating (endothelial) progenitor cells predict microvascular
      outcomes in T2D. Together with previous studies showing an association with
      cardiovascular events, these data indicate that CPCs/EPCs represent biomarkers of
      the global complication burden in diabetes.

PMID- 25942479
TI  - Cyclin E-Mediated Human Proopiomelanocortin Regulation as a Therapeutic Target
      for Cushing Disease.
AB  - CONTEXT: Cushing disease, due to pituitary corticotroph tumor ACTH
      hypersecretion, drives excess adrenal cortisol production with adverse morbidity
      and mortality. Loss of glucocorticoid negative feedback on the hypothalamic
      pituitary-adrenal axis leads to autonomous transcription of the corticotroph
      precursor hormone proopiomelanocortin (POMC), consequent ACTH overproduction, and
      adrenal hypercortisolism. We previously reported that R-roscovitine (CYC202,
      seliciclib), a 2,6,9-trisubstituted purine analog, suppresses cyclin-dependent
      kinase 2/cyclin E and inhibits ACTH in mice and zebrafish. We hypothesized that
      intrapituitary cyclin E signaling regulates corticotroph tumor POMC transcription
      independently of cell cycle progression. The aim was to investigate whether R
      roscovitine inhibits human ACTH in corticotroph tumors by targeting the cyclin
      dependent kinase 2/cyclin E signaling pathway. METHODS: Primary cell cultures of
      surgically resected human corticotroph tumors were treated with or without R
      roscovitine, ACTH measured by RIA and quantitative PCR, and/or Western blot
      analysis performed to investigate ACTH and lineage-specific transcription
      factors. Cyclin E and E2F transcription factor 1 (E2F1) small interfering RNA
      (siRNA) transfection was performed in murine corticotroph tumor AtT20 cells to
      elucidate mechanisms for drug action. POMC gene promoter activity in response to
      R-roscovitine treatment was analyzed using luciferase reporter and chromatin
      immunoprecipitation assays. RESULTS: R-roscovitine inhibits human corticotroph
      tumor POMC and Tpit/Tbx19 transcription with decreased ACTH expression. Cyclin E
      and E2F1 exhibit reciprocal positive regulation in corticotroph tumors. R
      roscovitine disrupts E2F1 binding to the POMC gene promoter and suppresses
      Tpit/Tbx19 and other lineage-specific POMC transcription cofactors via E2F1
      dependent and -independent pathways. CONCLUSION: R-roscovitine inhibits human
      pituitary corticotroph tumor ACTH by targeting the cyclin E/E2F1 pathway.
      Pituitary cyclin E/E2F1 signaling is a previously unappreciated molecular
      mechanism underlying neuroendocrine regulation of the hypothalamic-pituitary
      adrenal axis, providing a subcellular therapeutic target for small molecule
      cyclin-dependent kinase 2 inhibitors of pituitary ACTH-dependent
      hypercortisolism, ie, Cushing disease.

PMID- 25942478
TI  - The Gene of the Ubiquitin-Specific Protease 8 Is Frequently Mutated in Adenomas
      Causing Cushing's Disease.
AB  - CONTEXT: We have recently reported somatic mutations in the ubiquitin-specific
      protease USP8 gene in a small series of adenomas of patients with Cushing's
      disease. OBJECTIVE: To determine the prevalence of USP8 mutations and the
      genotype-phenotype correlation in a large series of patients diagnosed with
      Cushing's disease. DESIGN: We performed a retrospective, multicentric, genetic
      analysis of 134 functioning and 11 silent corticotroph adenomas using Sanger
      sequencing. Biochemical and clinical features were collected and examined within
      the context of the mutational status of USP8, and new mutations were
      characterized by functional studies. PATIENTS: A total of 145 patients who
      underwent surgery for an ACTH-producing pituitary adenoma. MAIN OUTCOMES
      MEASURES: Mutational status of USP8. Biochemical and clinical features included
      sex, age at diagnosis, tumor size, preoperative and postoperative hormonal
      levels, and comorbidities. RESULTS: We found somatic mutations in USP8 in 48
      (36%) pituitary adenomas from patients with Cushing's disease but in none of 11
      silent corticotropinomas. The prevalence was higher in adults than in pediatric
      cases (41 vs 17%) and in females than in males (43 vs 17%). Adults having USP8
      mutated adenomas were diagnosed at an earlier age than those with wild-type
      lesions (36 vs 44 y). Mutations were primarily found in adenomas of 10 +/- 7 mm
      and were inversely associated with the development of postoperative adrenal
      insufficiency. All the mutations affected the residues Ser718 or Pro720,
      including five new identified alterations. Mutations reduced the interaction
      between USP8 and 14-3-3 and enhanced USP8 activity. USP8 mutants diminished
      epidermal growth factor receptor ubiquitination and induced Pomc promoter
      activity in immortalized AtT-20 corticotropinoma cells. CONCLUSIONS: USP8 is
      frequently mutated in adenomas causing Cushing's disease, especially in those
      from female adult patients diagnosed at a younger age.

PMID- 25942481
TI  - CYP2R1 Mutations Impair Generation of 25-hydroxyvitamin D and Cause an Atypical
      Form of Vitamin D Deficiency.
AB  - CONTEXT: Production of the active vitamin D hormone 1,25-dihydroxyvitamin D
      requires hepatic 25-hydroxylation of vitamin D. The CYP2R1 gene encodes the
      principal vitamin D 25-hydroxylase in humans. OBJECTIVE: This study aimed to
      determine the prevalence of CYP2R1 mutations in Nigerian children with familial
      rickets and vitamin D deficiency and assess the functional effect on 25
      hydroxylase activity. DESIGN AND PARTICIPANTS: We sequenced the CYP2R1 gene in
      subjects with sporadic rickets and affected subjects from families in which more
      than one member had rickets. MAIN OUTCOME MEASURES: Function of mutant CYP2R1
      genes as assessed in vivo by serum 25-hydroxyvitamin D values after
      administration of vitamin D and in vitro by analysis of mutant forms of the
      CYP2R1. RESULTS: CYP2R1 sequences were normal in 27 children with sporadic
      rickets, but missense mutations were identified in affected members of 2 of 12
      families, a previously identified L99P, and a novel K242N. In silico analyses
      predicted that both substitutions would have deleterious effects on the variant
      proteins, and in vitro studies showed that K242N and L99P had markedly reduced or
      complete loss of 25-hydroxylase activity, respectively. Heterozygous subjects
      were less affected than homozygous subjects, and oral administration of vitamin D
      led to significantly lower increases in serum 25-hydroxyvitamin D in heterozygous
      than in control subjects, whereas homozygous subjects showed negligible
      increases. CONCLUSION: These studies confirm that CYP2R1 is the principal 25
      hydroxylase in humans and demonstrate that CYP2R1 alleles have dosage-dependent
      effects on vitamin D homeostasis. CYP2R1 mutations cause a novel form of genetic
      vitamin D deficiency with semidominant inheritance.

PMID- 25942482
TI  - Effect of Early Parenteral Nutrition on the HPA Axis and on Treatment With
      Corticosteroids in Intensive Care Patients.
AB  - BACKGROUND: Nutrition can affect the hypothalamus-pituitary-adrenal axis. We
      hypothesized that early administration of parenteral nutrition (PN) during
      critical illness reduces plasma ACTH and cortisol concentrations and thereby
      increases the use of corticosteroids. METHODS: This is a preplanned substudy of a
      randomized controlled trial (EPaNIC) that compared early PN with late PN in 4640
      critically ill patients. We investigated the effect of early vs late PN on any
      steroid treatment and on treatment for >= 5 days to capture patients with
      clinical suspicion of adrenal insufficiency, and assessed whether this was
      related to an effect on septic shock. Also, in a propensity score-matched
      subgroup (n=174) of patients not receiving steroids, plasma ACTH and (free)
      cortisol were quantified. RESULTS: Compared with late PN, more patients on early
      PN received treatment with corticosteroids (26.2% vs 23.8%; P = .05) and with
      corticosteroids for >= 5 days (14.0% vs 11.9%; P = .03). However, plasma ACTH and
      (free) cortisol concentrations were unaffected and thus could not explain the
      higher use of corticosteroids with early PN. Instead, more patients developed new
      septic shock with early PN (17.0%) than with late PN (14.2%) (P = .01). In
      multivariate logistic regression analysis, new septic shock was an independent
      determinant for >= 5 days steroid treatment (odds ratio, 6.25; 95% confidence
      interval, 4.93-7.94; P < .0001), statistically explaining the effect of early PN
      on steroid treatment. CONCLUSIONS: Early PN did not affect plasma concentrations
      of ACTH and (free) cortisol, but increased the incidence of septic shock, which
      statistically explained why more patients on early PN received corticosteroids.

PMID- 25942483
TI  - Huntingtin Is Required for Epithelial Polarity through RAB11A-Mediated Apical
      Trafficking of PAR3-aPKC.
AB  - The establishment of apical-basolateral polarity is important for both normal
      development and disease, for example, during tumorigenesis and metastasis. During
      this process, polarity complexes are targeted to the apical surface by a RAB11A
      dependent mechanism. Huntingtin (HTT), the protein that is mutated in Huntington
      disease, acts as a scaffold for molecular motors and promotes microtubule-based
      dynamics. Here, we investigated the role of HTT in apical polarity during the
      morphogenesis of the mouse mammary epithelium. We found that the depletion of HTT
      from luminal cells in vivo alters mouse ductal morphogenesis and lumen formation.
      HTT is required for the apical localization of PAR3-aPKC during epithelial
      morphogenesis in virgin, pregnant, and lactating mice. We show that HTT forms a
      complex with PAR3, aPKC, and RAB11A and ensures the microtubule-dependent apical
      vesicular translocation of PAR3-aPKC through RAB11A. We thus propose that HTT
      regulates polarized vesicular transport, lumen formation and mammary epithelial
      morphogenesis. 

PMID- 25942485
TI  - Energy crisis and the Hippo pathway.

PMID- 25942484
TI  - Moderate Hypothermia Significantly Decreases Hippocampal Cell Death Involving
      Autophagy Pathway after Moderate Traumatic Brain Injury.
AB  - Here, we evaluated changes in autophagy after post-traumatic brain injury (TBI)
      followed by moderate hypothermia in rats. Adult male Sprague-Dawley rats were
      randomly divided into four groups: sham injury with normothermia group (37 
      degrees C); sham injury with hypothermia group (32  degrees C); TBI with
      normothermia group (TNG; 37  degrees C); and TBI with hypothermia group (THG; 32 
      degrees C). Injury was induced by a fluid percussion TBI device. Moderate
      hypothermia (32  degrees C) was achieved by partial immersion in a water bath (0 
      degrees C) under general anesthesia for 4 h. All rats were killed at 24 h after
      fluid percussion TBI. The ipsilateral hippocampus in all rats was analyzed with
      hematoxylin and eosin staining; terminal deoxynucleoitidyl transferase-mediated
      nick end labeling staining was used to determine cell death in ipsilateral
      hippocampus. Immunohistochemistry and western blotting of microtubule-associated
      protein light chain 3 (LC3), Beclin-1, as well as transmission electron
      microscopy performed to assess changes in autophagy. At 24 h after TBI, the cell
      death index was 27.90 +/- 2.36% in TNG and 14.90 +/- 1.52% in THG. Expression
      level of LC3 and Beclin-1 were significantly increased after TBI and were further
      up-regulated after post-TBI hypothermia. Further, ultrastructural observations
      showed that there was a marked increase of autophagosomes and autolysosomes in
      ipsilateral hippocampus after post-TBI hypothermia. Our data demonstrated that
      moderate hypothermia significantly attenuated cell death and increased autophagy
      in ipsilateral hippocampus after fluid percussion TBI. In conclusion, autophagy
      pathway may participate in the neuroprotective effect of post-TBI hypothermia.

PMID- 25942486
TI  - Behavior of Multiclass Pesticide Residue Concentrations during the Transformation
      from Rose Petals to Rose Absolute.
AB  - This study investigates the concentrations of 54 multiclass pesticides during the
      transformation processes from rose petal to concrete and absolute using roses
      spiked with pesticides as a model. The concentrations of the pesticides were
      followed during the process of transforming the spiked rose flowers from an
      organic field into concrete and then into absolute. The rose flowers, the
      concrete, and the absolute, as well as their transformation intermediates, were
      analyzed for pesticide content using gas chromatography/tandem mass spectrometry.
      We observed that all the pesticides were extracted and concentrated in the
      absolute, with the exception of three molecules: fenthion, fenamiphos, and
      phorate. Typical pesticides were found to be concentrated by a factor of 100-300
      from the rose flowers to the rose absolute. The observed effect of pesticide
      enrichment was also studied in roses and their extracts from four classically
      phytosanitary treated fields. Seventeen pesticides were detected in at least one
      of the extracts. Like the case for the spiked samples in our model, the
      pesticides present in the rose flowers from Turkey were concentrated in the
      absolute. Two pesticides, methidathion and chlorpyrifos, were quantified in the
      rose flowers at approximately 0.01 and 0.01-0.05 mg kg(-1), respectively,
      depending on the treated field. The concentrations determined for the
      corresponding rose absolutes were 4.7 mg kg(-1) for methidathion and 0.65-27.25
      mg kg(-1) for chlorpyrifos. 

PMID- 25942487
TI  - Consumption of a polyphenol-rich grape-wine extract lowers ambulatory blood
      pressure in mildly hypertensive subjects.
AB  - Polyphenols in grape and wine have been suggested to contribute to the
      cardiovascular health benefits of the Mediterranean lifestyle. The reported
      effects of grape products on blood pressure (BP) remain, however, equivocal. In a
      double-blind placebo controlled crossover study, the effect of two grape extracts
      on BP and vascular function was assessed in 60 untreated, mildly hypertensive
      subjects after four weeks intervention. Both extracts (grape-red wine and grape
      alone) had high concentrations of anthocyanins and flavonols, but the grape alone
      was relatively poor in catechins and procyanidins. Parameters measured included
      ambulatory and office BP, flow-mediated vasodilation, arterial distensibility,
      platelet function and plasma lipoproteins. Results showed that 24-hour ambulatory
      systolic/diastolic BPs were significantly lower in the grape-wine extract
      intervention (135.9 +/- 1.3/84.7 +/- 0.8 mmHg; mean +/- SEM) compared to placebo
      (138.9 +/- 1.3/86.6 +/- 1.2 mmHg), predominantly during daytime. Plasma
      concentrations of the vasoconstrictor endothelin-1 decreased by 10%, but other
      measures of vascular function were not affected. Grape juice extract alone had no
      effect on BP or any measures of vascular function. Polyphenol-rich food products,
      and may be specifically catechins and procyanidins, may thus help sustain a
      healthy BP and contribute to the healthy Mediterranean lifestyle. 

PMID- 25942488
TI  - Enteral nutrition in pancreaticoduodenectomy: a literature review.
AB  - Pancreaticoduodenectomy (PD) is considered the gold standard treatment for
      periampullory carcinomas. This procedure presents 30%-40% of morbidity. Patients
      who have undergone pancreaticoduodenectomy often present perioperative
      malnutrition that is worse in the early postoperative days, affects the process
      of healing, the intestinal barrier function and the number of postoperative
      complications. Few studies focus on the relation between enteral nutrition (EN)
      and postoperative complications. Our aim was to perform a review, including only
      randomized controlled trial meta-analyses or well-designed studies, of evidence
      regarding the correlation between EN and main complications and outcomes after
      pancreaticoduodenectomy, as delayed gastric emptying (DGE), postoperative
      pancreatic fistula (POPF), postpancreatectomy hemorrhage (PPH), length of stay
      and infectious complications. Several studies, especially randomized controlled
      trial have shown that EN does not increase the rate of DGE. EN appeared safe and
      tolerated for patients after PD, even if it did not reveal any advantages in
      terms of POPF, PPH, length of stay and infectious complications. 

PMID- 25942489
TI  - alpha-Naphthoflavone Increases Lipid Accumulation in Mature Adipocytes and
      Enhances Adipocyte-Stimulated Endothelial Tube Formation.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated factor that regulates
      biological effects associated with obesity. The AhR agonists, such as
      environmental contaminants 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and beta
      naphthoflavone (BNF), inhibit preadipocyte differentiation and interfere with the
      functions of adipose tissue, whereas the antagonist may have opposite or
      protective effects in obesity. This study investigated the effects of alpha
      naphthoflavone (alpha-NF), an AhR antagonist, on adipogenesis- and angiogenesis
      associated factors in mature adipocytes and on cross-talk of mature adipocytes
      with endothelial cells (ECs). Besides, the roles of the AhR on lipid accumulation
      and on secretion of vascular endothelial growth factor were also determined by
      introducing siRNA of AhR. Differentiated 3T3-L1 cells were treated with alpha
      naphthoflavone (alpha-NF) (1-5 MUM) for 16 h. Lipid accumulation and the
      expressions of AhR-associated factors in the cells were determined. The
      interaction between adipocytes and ECs was investigated by cultivating ECs with
      conditioned medium (CM) from alpha-NF-treated mature adipocytes, followed by the
      determination of endothelial tube formation. The results showed that alpha-NF
      significantly increased triglyceride (TG) accumulation in mature adipocytes,
      which was associated with increased expression of hormone-sensitive lipase (HSL),
      estrogen receptor (ER), as well as decreased expression of AhR, AhR nuclear
      translocator (ARNT), cytochrome P4501B1 (CYP1B1), and nuclear factor erythroid-2
      related factor (NRF-2) proteins. In addition, CM stimulated formation of tube
      like structures in ECs, and alpha-NF further enhanced such stimulation in
      association with modulated the secretions of various angiogenic mediators by
      mature adipocytes. Similarly, increased TG accumulation and vascular endothelial
      growth factor (VEGF) secretion were observed in AhR-knockout cells. In
      conclusion, alpha-NF increased TG accumulation in mature adipocytes and enhanced
      mature adipocyte-stimulated tube formation in ECs, suggesting that the AhR may
      suppress obesity-induced adverse effects, and alpha-NF abolished the protective
      effects of the AhR. 

PMID- 25942490
TI  - Dietary RNAs: New Stories Regarding Oral Delivery.
AB  - microRNAs (miRNAs), a class of small RNAs, are important regulators of various
      developmental processes in both plants and animals. Several years ago, a report
      showed the detection of diet-derived plant miRNAs in mammalian tissues and their
      regulation of mammalian genes, challenging the traditional functions of plant
      miRNAs. Subsequently, multiple efforts have attempted to replicate these
      findings, with the results arguing against the uptake of plant dietary miRNAs in
      healthy consumers. Moreover, several reports suggest the potential for "false
      positive" detection of plant miRNAs in human tissues. Meanwhile, some research
      continues to suggest both the presence and function of dietary miRNAs in
      mammalian tissues. Here we review the recent literature and discuss the strengths
      and weaknesses of emerging work that suggests the feasibility of dietary delivery
      of miRNAs. We also discuss future experimental approaches to address this
      controversial topic. 

PMID- 25942492
TI  - A Telescreening Tool to Detect Aphasia in Patients with Stroke.
AB  - BACKGROUND: Early identification of patients with stroke-induced aphasia is
      essential because it is a significant disability affecting daily life and is
      linked to poor functional outcome after stroke. However, most patients with
      stroke are unable to undergo aphasia evaluation and detection and therefore
      remain undiagnosed. The purpose of this study is to develop a valid, reliable
      mobile aphasia screening test (MAST) for patients in remote locations. MATERIALS
      AND METHODS: To accomplish this, we enrolled patients with (n=30) and without
      (n=30) stroke-induced aphasia. A MAST, which adopted the Korean version of the
      shortened version of the Frenchay Aphasia Screening Test (K-FAST), was designed
      as an iPad((r)) (Apple, Cupertino, CA) application. To validate the MAST, we
      compared its performance with that of the Korean version of the Western Aphasia
      Battery (K-WAB) and conventional shortened FAST paper version (K-FAST). We
      analyzed interrater and internal reliability, using Cronbach's alpha coefficient,
      and assessed the diagnostic sensitivity, specificity, and power. RESULTS: There
      was significant correlation between K-FAST and MAST (intraclass correlation
      coefficient [ICC]=0.995, p<0.001). MAST also had a high correlation with K-WAB
      (ICC=0.752, p<0.001). Interrater reliability was very high (ICC=0.999, p<0.001).
      The test had high sensitivity (90.0%) and specificity (73.3%) with an accuracy of
      0.930 (95% confidence interval=0.853-1.000). The MAST is a valid and reliable
      tool for detecting aphasia in patients with stroke. CONCLUSIONS: This
      telescreening test may overcome the limitations of test administration and may be
      a convenient and cost-effective alternative to the existing aphasia screening
      tests for patients with stroke.

PMID- 25942491
TI  - Millennium development goal four and child health inequities in indonesia: a
      systematic review of the literature.
AB  - INTRODUCTION: Millennium Development Goal (MDG) 4 calls for reducing mortality of
      children under-five years by two-thirds by 2015. Indonesia is on track to
      officially meet the MDG 4 targets by 2015 but progress has been far from
      universal. It has been argued that national level statistics, on which MDG 4
      relies, obscure persistent health inequities within the country. Particularly
      inequities in child health are a major global public health challenge both for
      achieving MDG 4 in 2015 and beyond. This review aims to map out the situation of
      MDG 4 with respect to disadvantaged populations in Indonesia applying the Social
      Determinants of Health (SDH) framework. The specific objectives are to answer:
      Who are the disadvantaged populations? Where do they live? And why and how is the
      inequitable distribution of health explained in terms of the SDH framework?
      METHODS AND FINDINGS: We retrieved studies through a systematic review of peer
      reviewed and gray literature published in 1995-2014. The PRISMA-Equity 2012
      statement was adapted to guide the methods of this review. The dependent
      variables were MDG 4-related indicators; the independent variable "disadvantaged
      populations" was defined by different categories of social differentiation using
      PROGRESS. Included texts were analyzed following the guidelines for deductive
      content analysis operationalized on the basis of the SDH framework. We identified
      83 studies establishing evidence on more than 40 different determinants hindering
      an equitable distribution of child health in Indonesia. The most prominent
      determinants arise from the shortcomings within the rural health care system, the
      repercussions of food poverty coupled with low health literacy among parents, the
      impact of low household decision-making power of mothers, and the consequences of
      high persistent use of traditional birth attendants among ethnic minorities.
      CONCLUSION: This review calls for enhanced understanding of the determinants and
      pathways that create, detain, and overcome inequities in child health in resource
      constraint settings like Indonesia and the promotion of actionable health policy
      recommendations and tailored investments.

PMID- 25942493
TI  - The oldest record of ornithuromorpha from the early cretaceous of China.
AB  - Ornithuromorpha is the most inclusive clade containing extant birds but not the
      Mesozoic Enantiornithes. The early evolutionary history of this avian clade has
      been advanced with recent discoveries from Cretaceous deposits, indicating that
      Ornithuromorpha and Enantiornithes are the two major avian groups in Mesozoic.
      Here we report on a new ornithuromorph bird, Archaeornithura meemannae gen. et
      sp. nov., from the second oldest avian-bearing deposits (130.7 Ma) in the world.
      The new taxon is referable to the Hongshanornithidae and constitutes the oldest
      record of the Ornithuromorpha. However, A. meemannae shows few primitive features
      relative to younger hongshanornithids and is deeply nested within the
      Hongshanornithidae, suggesting that this clade is already well established. The
      new discovery extends the record of Ornithuromorpha by five to six million years,
      which in turn pushes back the divergence times of early avian lingeages into the
      Early Cretaceous. 

PMID- 25942495
TI  - Next-Generation Sequencing Analysis Reveals Differential Expression Profiles of
      MiRNA-mRNA Target Pairs in KSHV-Infected Cells.
AB  - Kaposi's sarcoma associated herpesvirus (KSHV) causes several tumors, including
      primary effusion lymphoma (PEL) and Kaposi's sarcoma (KS). Cellular and viral
      microRNAs (miRNAs) have been shown to play important roles in regulating gene
      expression. A better knowledge of the miRNA-mediated pathways affected by KSHV
      infection is therefore important for understanding viral infection and tumor
      pathogenesis. In this study, we used deep sequencing to analyze miRNA and
      cellular mRNA expression in a cell line with latent KSHV infection (SLKK) as
      compared to the uninfected SLK line. This approach revealed 153 differentially
      expressed human miRNAs, eight of which were independently confirmed by qRT-PCR.
      KSHV infection led to the dysregulation of ~15% of the human miRNA pool and most
      of these cellular miRNAs were down-regulated, including nearly all members of the
      14q32 miRNA cluster, a genomic locus linked to cancer and that is deleted in a
      number of PEL cell lines. Furthermore, we identified 48 miRNAs that were
      associated with a total of 1,117 predicted or experimentally validated target
      mRNAs; of these mRNAs, a majority (73%) were inversely correlated to expression
      changes of their respective miRNAs, suggesting miRNA-mediated silencing
      mechanisms were involved in a number of these alterations. Several dysregulated
      miRNA-mRNA pairs may facilitate KSHV infection or tumor formation, such as up
      regulated miR-708-5p, associated with a decrease in pro-apoptotic caspase-2 and
      leukemia inhibitory factor LIF, or down-regulated miR-409-5p, associated with an
      increase in the p53-inhibitor MDM2. Transfection of miRNA mimics provided further
      evidence that changes in miRNAs are driving some observed mRNA changes. Using
      filtered datasets, we also identified several canonical pathways that were
      significantly enriched in differentially expressed miRNA-mRNA pairs, such as the
      epithelial-to-mesenchymal transition and the interleukin-8 signaling pathways.
      Overall, our data provide a more detailed understanding of KSHV latency and guide
      further studies of the biological significance of these changes. 

PMID- 25942496
TI  - Sweet tasting solutions for reduction of needle-related procedural pain in
      children aged one to 16 years.
AB  - BACKGROUND: Extensive evidence exists showing analgesic effects of sweet
      solutions for newborns and infants. It is less certain if the same analgesic
      effects exist for children one year to 16 years of age. This is an updated
      version of the original Cochrane review published in Issue 10, 2011 (Harrison
      2011) titled Sweet tasting solutions for reduction of needle-related procedural
      pain in children aged one to 16 years. OBJECTIVES: To determine the efficacy of
      sweet tasting solutions or substances for reducing needle-related procedural pain
      in children beyond one year of age. SEARCH METHODS: Searches were run to the end
      of June 2014. We searched the following databases: the Cochrane Central Register
      of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews, Database
      of Abstracts of Reviews of Effects (DARE), Cochrane Methodology Register, Health
      Technology Assessment, the NHS Economic Evaluation Database, MEDLINE, EMBASE,
      PsycINFO, and ACP Journal Club (all via OvidSP), and CINAH (via EBSCOhost). We
      applied no language restrictions. SELECTION CRITERIA: Published or unpublished
      randomised controlled trials (RCT) in which children aged one year to 16 years,
      received a sweet tasting solution or substance for needle-related procedural
      pain. Control conditions included water, non-sweet tasting substances, pacifier,
      distraction, positioning/containment, breastfeeding, or no treatment. DATA
      COLLECTION AND ANALYSIS: Outcome measures included crying duration, composite
      pain scores, physiological or behavioral pain indicators, self-report of pain or
      parental or healthcare professional-report of the child's pain. We reported mean
      differences (MD), weighted mean difference (WMD), or standardized mean difference
      (SMD) with 95% confidence intervals (CI) using fixed-effect or random-effects
      models as appropriate for continuous outcome measures. We reported risk ratio
      (RR), risk difference (RD), and the number needed to treat to benefit (NNTB) for
      dichotomous outcomes. We used the I(2) statistic to assess between-study
      heterogeneity. MAIN RESULTS: We included one unpublished and seven published
      studies (total of 808 participants); four more studies and 478 more participants
      than the 2011 review. Six trials included young children aged one to four years
      receiving sucrose or candy lollypops for immunisation pain compared with water or
      no treatment. Usual care included topical anaesthetics, upright parental holding,
      and distraction. All studies were well designed blinded RCTs, however, five of
      the six studies had a high risk of bias based on small sample sizes.Two studies
      included school-aged children receiving sweet or unsweetened chewing gum before,
      or before and during, immunisation and blood collection. Both studies, conducted
      by the same author, had a high risk of bias based on small sample sizes.Results
      for the toddlers/pre-school children were conflicting. Duration of cry, using a
      random-effects model, was not significantly reduced by sweet taste (six trials,
      520 children, WMD -15 seconds, 95% CI -54 to 24, I(2) = 94%).Composite pain score
      at time of first needle was reported in four studies (n = 121 children). The
      scores were not significantly different between the sucrose and control group
      (SMD -0.26, 95% CI -1.27 to 0.75, I(2) = 86%).A Children's Hospital of Eastern
      Ontario Pain Scale score > 4 was significantly less common in the sucrose group
      compared to the control group in one study (n = 472, RR 0.55, 95% CI 0.45 to
      0.67; RD -0.29, 95% CI -0.37 to -0.20; NNTB 3, 95% CI 3 to 5; tests for
      heterogeneity not applicable.For school-aged children, chewing sweet gum before
      needle-related painful procedures (two studies, n = 111 children) or during the
      procedures (two studies, n = 103 children) did not significantly reduce pain
      scores. A comparison of the Faces Pain Scale scores in children chewing sweet gum
      before the procedures compared with scores of children chewing unsweetened gum
      revealed a WMD of -0.15 (95% CI -0.61 to 0.30). Similar results were found when
      comparing the chewing of sweet gum with unsweetened gum during the procedure (WMD
      0.23, 95% CI -0.28 to 0.74). The Colored Analogue Scale for children chewing
      sweet gum compared to unsweetened gum before the procedure was not significantly
      different (WMD 0.24 (-0.69 to 1.18)) nor was it different when children chewed
      the gum during the procedure (WMD 0.86 (95% CI -0.12 to 1.83)). There was no
      heterogeneity for any of these analyses in school-aged children (I(2) = 0%).
      AUTHORS' CONCLUSIONS: Based on the eight studies included in this systematic
      review update, two of which were subgroups of small numbers of eligible toddlers
      from larger studies, and three of which were pilot RCTs with small numbers of
      participants, there is insufficient evidence of the analgesic effects of sweet
      tasting solutions or substances during acutely painful procedures in young
      children between one and four years of age. Further rigorously conducted,
      adequately powered RCTs are warranted in this population. Based on the two
      studies by the same author, there was no evidence of analgesic effects of sweet
      taste in school-aged children. As there are other effective evidence-based
      strategies available to use in this age group, further trials are not
      warranted.Despite the addition of four studies in this review, conclusions have
      not changed since the last version of the review.

PMID- 25942497
TI  - The Plasmid Complement of the Cheese Isolate Lactococcus garvieae IPLA 31405
      Revealed Adaptation to the Dairy Environment.
AB  - Lactococcus garvieae is a lactic acid bacterium found in raw-milk dairy products
      as well as a range of aquatic and terrestrial environments. The plasmids in L.
      garvieae have received little attention compared to those of dairy Lactococcus
      lactis, in which the genes carried by these extrachromosomal elements are
      considered of adaptive value. The present work reports the sequencing and
      analysis of the plasmid complement of L. garvieae IPLA 31405, a strain isolated
      from a traditional, Spanish, starter-free cheese made from raw-milk. It consists
      of pLG9 and pLG42, of 9,124 and 42,240 nucleotides, respectively. Based on
      sequence and structural homology in the putative origin of replication (ori)
      region, pLG9 and pLG42 are predicted to replicate via a theta mechanism. Real
      time, quantitative PCR showed the number of copies per chromosome equivalent of
      pLG9 and pLG42 to be around two and five, respectively. Sequence analysis
      identified eight complete open reading frames (orfs) in pLG9 and 36 in pLG42;
      these were organized into functional modules or cassettes containing different
      numbers of genes. These modules were flanked by complete or interrupted insertion
      sequence (IS)-like elements. Among the modules of pLG42 was a gene cluster
      encoding specific components of a phosphoenolpyruvate-phosphotransferase (PEP
      PTS) system, including a phospho-beta-galacosidase. The cluster showed a complete
      nucleotide identity respect to that in plasmids of L. lactis. Loss of pLG42
      showed this to be involved in lactose assimilation. In the same plasmid, an
      operon encoding a type I restriction/modification (R/M) system was also
      identified. The specificity of this R/M system might be broadened by different
      R/M specificity subunits detected in pLG9 and in the bacterial chromosome.
      However, challenges of L. garvieae IPLA 31405 against L. lactis phages proved
      that the R/M system was not involved in phage resistance. Together, these results
      support the hypothesis that, as in L. lactis, pLG42 contribute towards the
      adaptation of L. garvieae to the dairy environment. 

PMID- 25942499
TI  - Formation of urban fine particulate matter.

PMID- 25942498
TI  - 8-Triazolylpurines: Towards Fluorescent Inhibitors of the MDM2/p53 Interaction.
AB  - Small molecule nonpeptidic mimics of alpha-helices are widely recognised as
      protein-protein interaction (PPIs) inhibitors. Protein-protein interactions
      mediate virtually all important regulatory pathways in a cell, and the ability to
      control and modulate PPIs is therefore of great significance to basic biology,
      where controlled disruption of protein networks is key to understanding network
      connectivity and function. We have designed and synthesised two series of 2,6,9
      substituted 8-triazolylpurines as alpha-helix mimetics. The first series was
      designed based on low energy conformations but did not display any biological
      activity in a biochemical fluorescence polarisation assay targeting MDM2/p53.
      Although solution NMR conformation studies demonstrated that such molecules could
      mimic the topography of an alpha-helix, docking studies indicated that the same
      compounds were not optimal as inhibitors for the MDM2/p53 interaction. A new
      series of 8-triazolylpurines was designed based on a combination of docking
      studies and analysis of recently published inhibitors. The best compound
      displayed low micromolar inhibitory activity towards MDM2/p53 in a biochemical
      fluorescence polarisation assay. In order to evaluate the applicability of these
      compounds as biologically active and intrinsically fluorescent probes, their
      absorption/emission properties were measured. The compounds display fluorescent
      properties with quantum yields up to 50%. 

PMID- 25942500
TI  - 4-Fluoro and 4-Hydroxy Pyrrolidine-thioxotetrahydropyrimidinones: Organocatalysts
      for Green Asymmetric Transformations in Brine.
AB  - The synthesis of both trans- and cis-diastereomers of pyrrolidinine
      thioxotetrahydropyrimidinone bearing either a fluorine or a hydroxyl group was
      accomplished. The new compounds were tested for their catalytic properties in a
      variety of asymmetric organic transformations and compared with the first
      generation catalyst. It was found that the new catalysts could efficiently
      catalyze the reactions in brine, without the use of organic solvent, and by
      employing an almost stoichiometric amount of reagents. Thus, the products were
      isolated by simple extractions, avoiding the use of chromatography in excellent
      yields, diastereoselectivities, and enantioselectivities. 

PMID- 25942501
TI  - Biological activities of Peristrophe bivalvis extracts: promising potential for
      anti-snake venoms against Naja kaouthia and Trimeresurus albolabris venoms.
AB  - This study evaluates the in vitro anti-snake venom potential of Peristrophe
      bivalvis (PB) extracts against Naja kaouthia (NK) and Trimeresurus albolabris
      (TA) venoms, including inhibition of cytotoxic effects and enzymatic activities,
      and the binding-precipitation of extracts and venom proteins analysis. In
      addition, the antioxidant, cytotoxic and in vivo acute oral toxic activities of
      PB extracts are also reported. The in vitro cytotoxic and enzymatic analysis
      reveals that the ethanol extracts of stems and leaves of PB showed good anti
      snake venom activity against NK and TA venoms. In addition, the antioxidant
      result indicated that only the ethanol extract of leaves exhibited weak DPPH
      radical-scavenging activity. The ethanol whole-plant extract of PB also showed no
      cytotoxicity against four cell lines. Moreover, the in vivo acute oral toxicity
      result of the ethanol whole-plant extract showed that all treated rats did not
      exhibit abnormal toxic signs or deaths.

PMID- 25942502
TI  - Somatostatin Analogs Treated Small Intestinal Neuroendocrine Tumor Patients
      Circulating MicroRNAs.
AB  - We previously detected and investigated nine altered microRNAs in small
      intestinal neuroendocrine tumor (SI-NET) tissues at different stages of disease.
      The aims of this study are to: 1) analyze whether SI-NET tissue microRNAs can be
      also detected in patient serum samples, 2) investigate a potential somatostatin
      analogs (SSAs) role on microRNA levels regulation in SSA-treated patient samples
      and 3) elucidate whether the serum microRNA levels in samples collected in
      different hospitals are predictable and steady. Our results show that tissue
      microRNAs are detectable in patient serum samples, and miR-96, -182, -183, -196a
      and -200a levels are lower in SI-NET untreated patients than in SSA-treated
      patients at all different stages. Conversely, miR-31, -129-5p, -133a and -215
      levels do not show any difference in untreated SI-NET patients and SSA-treated
      patients at all different stages. Our findings also show that miR-200a exhibits
      an atypical behavior with high levels in both untreated and SSA-treated patients
      at liver metastasis stage, and unequivocally never at the earlier stages. Serum
      samples collected in two hospitals keep alike microRNA level pattern, elucidating
      that the results are not dependent on samples handling. In conclusion, SI-NET
      tissue microRNAs are always detectable in untreated and SSA-treated patient serum
      samples, SSAs play an unknown role in eliciting SSA-treated patients' microRNA
      levels higher than in untreated patients, and this study enlightens that miR-200a
      might be involved in the liver metastasis during SI-NET progression. 

PMID- 25942504
TI  - CO2 sensing of La0.875Ca0.125FeO3 in wet vapor: a comparison of experimental
      results and first-principles calculations.
AB  - Experimental results show that with an increase of relative humidity, the
      resistance of La0.875Ca0.125FeO3 decreases at room temperature but increases at
      higher temperatures (140-360  degrees C). The humid effect at room temperature is
      due to the movement of H(+) or H3O(+) inside of the condensed water layer on the
      surface of La0.875Ca0.125FeO3. Regarding the humid effect at high temperatures,
      the density functional theory (DFT) calculations show that H2O can be adsorbed
      onto the La0.875Ca0.125FeO3 surface in the molecular and dissociative adsorption
      configurations, where the La0.875Ca0.125FeO3 surface gains some electrons from
      H2O or its dissociative products, consistent with our observation. Experimental
      results also show that CO2 sensing response at high temperatures decreases with
      an increase of room-temperature relative humidity. DFT calculations indicate that
      CO2 adsorbed onto the La0.875Ca0.125FeO3(010) surface, where high concentration
      oxygen adsorption occurs without water adsorption nearby, releases some electrons
      into the semiconductor surface, playing the role of a donor. The interaction
      between CO2 and the local La0.875Ca0.125FeO3(010) surface with pre-adsorption of
      H2O nearby results in some electron transfer from the La0.875Ca0.125FeO3 surface
      to CO2, which is responsible for the weakening of CO2 response at high
      temperatures for La0.875Ca0.125FeO3 with an increase of room-temperature relative
      humidity. 

PMID- 25942503
TI  - Diagnostic Accuracy of Quantitative and Qualitative Phase-Contrast Imaging for
      the ex Vivo Characterization of Human Coronary Atherosclerotic Plaques.
AB  - PURPOSE: To investigate the accuracy of x-ray grating interferometry phase
      contrast (PC) imaging for the characterization of human coronary artery plaque.
      MATERIALS AND METHODS: PC and conventional absorption computed tomographic (CT)
      imaging was performed ex vivo in this institutional review board-approved study
      in 40 human coronary artery segments by using a synchrotron radiation source.
      Qualitative analyses and calculations of image quality (McNemar test), plaque
      components (McNemar test), and plaque classification (Cohen kappa test) according
      to the American Heart Association classification were performed in 38 plaques
      detected at histopathologic examination (reference standard). Quantitative
      measurements of plaque components (ie, collagen, lipids, smooth muscle, and
      calcifications) were compared among PC and absorption images by using analysis of
      variance for repeated measures with post hoc Bonferroni correction. RESULTS:
      Image quality was superior in PC (median image score, 1) in all cases (100%)
      compared with absorption imaging (median image score, 3) (P < .001). Plaque
      components were detected by means of PC without significant differences (seven of
      seven calcifications, 22 of 22 plaques with collagen and smooth muscle cells, P >
      .99; 29 of 29 plaques with lipids, P = .10) with histopathologic findings,
      whereas absorption imaging was used to detect calcifications (seven of seven, P >
      .99) without statistical differences only (nine of 29 plaques with lipids, 0 of
      22 plaques with collagen and smooth muscle cells, P < .001). Accuracy for plaque
      stage assessment with PC (early vs advanced) was 100%, and characterization was
      correct in 33 of 38 plaques (87%), while conventional absorption imaging allowed
      correct characterization of seven plaques only (18%, P < .001). PC CT numbers
      were significantly different (P < .05) for all plaque components (mean for
      calcifications, 1236 HU +/- 69; collagen, 78 HU +/- 24; lipids, -18 HU +/- 23;
      and smooth muscle cells, 34 HU +/- 12), whereas absorption images showed
      significant differences (P < .001) between calcifications (1336 HU +/- 241) and
      other plaque components, but not for collagen (22 HU +/- 13), lipids (-15 HU +/-
      14), and smooth muscle (13 HU +/- 9) (P > .99). CONCLUSION: PC imaging allows
      accurate characterization of human coronary artery plaques and quantitative
      assessment of plaque components, thereby outperforming absorption imaging.

PMID- 25942505
TI  - Engineered crumpled graphene oxide nanocomposite membrane assemblies for advanced
      water treatment processes.
AB  - In this work, we describe multifunctional, crumpled graphene oxide (CGO) porous
      nanocomposites that are assembled as advanced, reactive water treatment
      membranes. Crumpled 3D graphene oxide based materials fundamentally differ from
      2D flat graphene oxide analogues in that they are highly aggregation and
      compression-resistant (i.e., pi-pi stacking resistant) and allow for the
      incorporation (wrapping) of other, multifunctional particles inside the 3D,
      composite structure. Here, assemblies of nanoscale, monomeric CGO with
      encapsulated (as a quasi core-shell structure) TiO2 (GOTI) and Ag (GOAg)
      nanoparticles, not only allow high water flux via vertically tortuous
      nanochannels (achieving water flux of 246 +/- 11 L/(m(2).h.bar) with 5.4 MUm
      thick assembly, 7.4 g/m(2)), outperforming comparable commercial ultrafiltration
      membranes, but also demonstrate excellent separation efficiencies for model
      organic and biological foulants. Further, multifunctionality is demonstrated
      through the in situ photocatalytic degradation of methyl orange (MO), as a model
      organic, under fast flow conditions (tres < 0.1 s); while superior antimicrobial
      properties, evaluated with GOAg, are observed for both biofilm (contact) and
      suspended growth scenarios (>3 log effective removal, Escherichia coli). This is
      the first demonstration of 3D, crumpled graphene oxide based nanocomposite
      structures applied specifically as (re)active membrane assemblies and highlights
      the material's platform potential for a truly tailored approach for next
      generation water treatment and separation technologies. 

PMID- 25942506
TI  - Framing risks and benefits of medical tourism: a content analysis of medical
      tourism coverage in Korean American community newspapers.
AB  - This study examines Korean American community newspapers' representation of risks
      and benefits involved with medical tourism offered in Korea. Using framing
      theory, this research attempts to explain Korean Americans' highly positive
      perceptions and high willingness to use health and medical services in Korea
      through medical tourism rather than using such services in the United States. The
      result of content analyses indicated that Korean American community newspapers
      are rarely engaged in risk communication and lack sufficient information about
      potential risks of medical tourism while emphasizing diverse benefits. Korean
      ethnic media, as the primary source of health communication for Korean Americans,
      should provide more reliable health and medical information for the population's
      appropriate health management. 

PMID- 25942507
TI  - Limitations of Daily Living Activities in Patients With Venous Stasis Ulcers
      Undergoing Compression Bandaging: Problems With the Concept of Self-bandaging.
AB  - Venous stasis ulcers (VSUs) represent both an enormous cost to the healthcare
      system and significant quality-of-life issue to patients. While certain high
      technology products have shown promise, compression bandaging continues to be the
      gold standard of care. Recently, some regional Medicare carriers suggested that
      patients with VSUs should be able to perform self-bandaging in an effort to avoid
      reimbursing caregivers to provide this service. Using a database of 7251 patients
      from 29 wound care facilities maintained as part of an agreement under the
      Intellicure Research Consortium for users of Intellicure Inc's (The Woodlands,
      Tex) wound care software; activity of daily living (ADL) data was extracted for
      all patients with a VSU in whom this was collected (547 patients) to examine such
      an impact. Analysis showed that 55% of these patients required assistance with
      ADLs-the majority had issues with dressing and toileting. It is unlikely that
      patients who require assistance with dressing and toileting will be able to
      achieve adequate positioning to perform self-bandaging. Since it is possible that
      even patients who do not require assistance with ADLs might be unable to perform
      self-bandaging, the authors consider these results a conservative estimation.
      These results indicate that a significant number of patients are not capable of
      self-bandaging, thus placing their prognosis and quality-of-life at risk if they
      are unable to pay for the necessary professional services or do not have family
      members who are capable of bandaging. 

PMID- 25942508
TI  - Extracellular Wound Matrix (OASIS(r)): Exploring the Contraindications. Results
      of Its Use in 32 Consecutive Outpatient Clinic Cases.
AB  - Background. In the authors' experience re-epithelialization after successful
      debridement and granulation can be the most difficult part of the wound closure
      process. Extracellular matrix products represent a possible solution. However, in
      studies discussing the effectiveness of extracellular wound matrix (porcine
      derived small intestine submucosa [SIS], [OASIS(r) Wound Matrix, Healthpoint Ltd,
      Fort Worth, Tex]), a long list of exclusion criteria has been presented. The
      present study was designed to explore the contraindications of OASIS Wound
      Matrix. METHODS: In this study, 32 patients in whom the wounds were fully
      debrided and granulated were treated with weekly applications of the wound
      matrix. The exclusion criteria formulated in the reported literature were
      followed. Seven different outcomes were defined. Various patient and wound
      characteristics that might influence outcome were recorded. RESULTS: Beneficial
      outcomes were seen in 80.6 % (n = 25) of the patients. The two main complications
      seen were infection and hypergranulation tissue. Infection was seen in 7 patients
      (22.6%). Four patients (57.1%) had an unsuccessful outcome. Hypergranulation
      tissue occurred in another 7 patients (22.6%) after a couple of applications.
      They all had a beneficial outcome. CONCLUSION: Much of the exclusion criteria
      used in previous reports are too strict. Infection should be the only absolute
      contraindication for starting treatment with OASIS, and it is a good reason to
      discontinue treatment with an ECM. Hypergranulation tissue (22.6%) is an easily
      treatable complication that has no negative influence on outcome. Some wounds
      (77.4%) had no complications, or had easily treatable complications that did not
      negatively influence the outcome.

PMID- 25942509
TI  - Open window thoracostomy: a new therapeutic option using topical negative
      pressure wound therapy.
AB  - Open window thoracostomy (OWT) is an invasive treatment option for thoracic
      empyema that is seldom indicated. These wounds are accompanied with a prolonged
      hospital stay and significant patient discomfort over an extended period of time.
      A retrospective report was conducted on patients who underwent OWT at the
      Academic Medical Center (Amsterdam, The Netherlands) and evaluated if topical
      negative pressure therapy ([TNP], V.A.C.(r) TherapyTM, KCI Medical BV, Houten,
      The Netherlands) is a valid treatment option for these wounds. Clinical outcome
      and applied management methods are analyzed. Between January 1986 and June 2005,
      15 patients, with a mean age of 54 years, were treated with OWT. Recently, the
      authors have used TNP in combination with OWT as a new treatment modality to
      obtain rapid control over pleural bacterial load and to achieve a well
      vascularized wound surface. Good clinical results and a trend toward shorter
      hospital stays and improved quality of life were seen. Open window thoracostomy
      as a treatment modality for thoracic empyema is a valid option but only when
      other means fail or are contraindicated. Treatment of open window thoracostomy in
      combination with TNP is a safe and adequate therapeutic option for thoracic
      empyema resulting in improved quality of life and overall shorter hospital stay. 

PMID- 25942510
TI  - Effect of Occlusion and Semi-occlusion on Experimental Skin Wound Healing: A
      Reevaluation.
AB  - The benefits of occlusive and/or semi-occlusive dressings to accelerate
      epidermal wound healing have been documented in experiments on human and animal
      models, as well as in clinical settings. Their benefits have been generally
      accepted. However, reports either from experimental or clinical observations
      suggest that occlusive dressings may occasionally delay wound healing. METHODS:
      Data presented here were reevaluated from experimental models conducted on
      controlled wounds. CONCLUSION: Although most human studies document that
      occlusive dressings facilitate epidermal wound healing, sufficient observations
      suggest that some experiment factors (latex rather than plastic and species) were
      not investigated in the earlier occlusive dressing observations, mandating the
      need for clarification. The differences between the earlier and more recent,
      significantly different, observations may relate to species (largely mouse rather
      than human), occlusive materials (latex rather than plastic), and type of wound
      (split-thickness versus stripping).

PMID- 25942511
TI  - Tissue engineering and wound healing: an overview of the past, present, and
      future.
AB  - Tissue engineering is described as the application of principles and methods of
      engineering and biology toward fundamental understanding of structure-function
      relationships in normal and pathological mammalian tissue. With this in mind,
      interest in applying tissue engineering in the evolving field of wound healing
      arose in the nineties of the previous century. This review provides an overview
      of the history and technique of tissue engineering, current wound healing related
      research, description of available tissue-engineered wound dressings, and future
      challenges. 

PMID- 25942512
TI  - Evolution of anti-IgE treatment.

PMID- 25942513
TI  - Development of an antibody that neutralizes soluble IgE and eliminates IgE
      expressing B cells.
AB  - Immunoglobulin E (IgE) plays a key role in allergic asthma and is a clinically
      validated target for monoclonal antibodies. Therapeutic anti-IgE antibodies block
      the interaction between IgE and the Fc epsilon (Fcepsilon) receptor, which
      eliminates or minimizes the allergic phenotype but does not typically curtail the
      ongoing production of IgE by B cells. We generated high-affinity anti-IgE
      antibodies (MEDI4212) that have the potential to both neutralize soluble IgE and
      eliminate IgE-expressing B-cells through antibody-dependent cell-mediated
      cytotoxicity. MEDI4212 variants were generated that contain mutations in the Fc
      region of the antibody or alterations in fucosylation in order to enhance the
      antibody's affinity for FcgammaRIIIa. All MEDI4212 variants bound to human IgE
      with affinities comparable to the wild-type (WT) antibody. Each variant was shown
      to inhibit the interaction between IgE and FcepsilonRI, which translated into
      potent inhibition of FcgammaRI-mediated function responses. Importantly, all
      variants bound similarly to IgE at the surface of membrane IgE expressing cells.
      However, MEDI4212 variants demonstrated enhanced affinity for FcgammaRIIIa
      including the polymorphic variants at position 158. The improvement in
      FcgammaRIIIa binding led to increased effector function in cell based assays
      using both engineered cell lines and class switched human IgE B cells. Through
      its superior suppression of IgE, we anticipate that effector function enhanced
      MEDI4212 may be able to neutralize high levels of soluble IgE and provide
      increased long-term benefit by eliminating the IgE expressing B cells before they
      differentiate and become IgE secreting plasma cells.

PMID- 25942515
TI  - "LOCK"ing up allergic responses with a Polish probiotic.

PMID- 25942516
TI  - Problematic game play: the diagnostic value of playing motives, passion, and
      playing time in men.
AB  - Internet gaming disorder is currently listed in the DSM-not in order to diagnose
      such a disorder but to encourage research to investigate this phenomenon. Even
      whether it is still questionable if Internet Gaming Disorder exists and can be
      judged as a form of addiction, problematic game play is already very well
      researched to cause problems in daily life. Approaches trying to predict
      problematic tendencies in digital game play have mainly focused on playing time
      as a diagnostic criterion. However, motives to engage in digital game play and
      obsessive passion for game play have also been found to predict problematic game
      play but have not yet been investigated together. The present study aims at (1)
      analyzing if obsessive passion can be distinguished from problematic game play as
      separate concepts, and (2) testing motives of game play, passion, and playing
      time for their predictive values for problematic tendencies. We found (N = 99
      males, Age: M = 22.80, SD = 3.81) that obsessive passion can be conceptually
      separated from problematic game play. In addition, the results suggest that
      compared to solely playing time immersion as playing motive and obsessive passion
      have added predictive value for problematic game play. The implications focus on
      broadening the criteria in order to diagnose problematic playing. 

PMID- 25942514
TI  - Colonization of germ-free mice with a mixture of three lactobacillus strains
      enhances the integrity of gut mucosa and ameliorates allergic sensitization.
AB  - Increasing numbers of clinical trials and animal experiments have shown that
      probiotic bacteria are promising tools for allergy prevention. Here, we analyzed
      the immunomodulatory properties of three selected lactobacillus strains and the
      impact of their mixture on allergic sensitization to Bet v 1 using a gnotobiotic
      mouse model. We showed that Lactobacillus (L.) rhamnosus LOCK0900, L. rhamnosus
      LOCK0908 and L. casei LOCK0919 are recognized via Toll-like receptor 2 (TLR2) and
      nucleotide-binding oligomerization domain-containing protein 2 (NOD2) receptors
      and stimulate bone marrow-derived dendritic cells to produce cytokines in species
      and strain-dependent manners. Colonization of germ-free (GF) mice with a mixture
      of all three strains (Lmix) improved the intestinal barrier by strengthening the
      apical junctional complexes of enterocytes and restoring the structures of
      microfilaments extending into the terminal web. Mice colonized with Lmix and
      sensitized to the Bet v 1 allergen showed significantly lower levels of allergen
      specific IgE, IgG1 and IgG2a and an elevated total IgA level in the sera and
      intestinal lavages as well as an increased transforming growth factor (TGF)-beta
      level compared with the sensitized GF mice. Splenocytes and mesenteric lymph node
      cells from the Lmix-colonized mice showed the significant upregulation of TGF
      beta after in vitro stimulation with Bet v 1. Our results show that Lmix
      colonization improved the gut epithelial barrier and reduced allergic
      sensitization to Bet v 1. Furthermore, these findings were accompanied by the
      increased production of circulating and secretory IgA and the regulatory cytokine
      TGF-beta. Thus, this mixture of three lactobacillus strains shows potential for
      use in the prevention of increased gut permeability and the onset of allergies in
      humans. 

PMID- 25942517
TI  - Letter to the Editor: Comment on Bevacizumab Treatment for Acute Branch Retinal
      Vein Occlusion Accompanied by Subretinal Hemorrhage.

PMID- 25942518
TI  - The stability of amino-functionalized polyhedral oligomeric silsesquioxanes in
      water.
AB  - Octa(aminopropylsilsesquioxane) Si8O12[(CH2)3NH2]8 is a very important precursor
      for many other hybrid organic/inorganic polyhedral oligomeric silsesquioxanes
      (POSS) because of the reactivity of its primary amine groups. Unfortunately, it
      is unstable in water, which can lead to the cleavage of its siloxane cage. In the
      present work, such a degradation was confirmed using solid-state (29)Si NMR
      spectroscopy, and the molecular features at the basis of this instability were
      studied using molecular dynamics simulations (MD). It was also investigated
      whether replacing the primary amine end groups by secondary amines or by amides
      with long aliphatic chains could lead to an improvement in the water stability of
      the Si/O framework. In the pure bulk models, all POSS interdigitate with their
      pendant organic arms intertwined. Upon insertion of isolated molecules into
      water, the dimensions of the primary amine POSS remain close to those of the
      bulk, while the secondary amine and the amide POSS favor conformations that
      optimize the intramolecular chain-chain interactions. When there are several POSS
      molecules in water, they cluster with each other through both intra- and
      intermolecular chain-chain interactions. This tendency for the organic chains to
      intertwine whenever possible provides some protection to the siloxane cages from
      water, but also leaves some of the siloxane O exposed. As such, the latter are
      accessible to form transient hydrogen bonds with the water molecules, which could
      be a precursor step to hydrolysis and thus cage breakage. In the molecular
      models, a better protection was obtained in the amide POSS for two reasons: its
      chains tended to wrap efficiently around its cage, and its ketone O kept water
      from getting close to the siloxanes. The molecular modeling characterizations
      were found to agree very well with experimental evidence. 

PMID- 25942519
TI  - Effects of GA3 on Plant Physiological Properties, Extraction, Subcellular
      Distribution and Chemical Forms of Pb in Lolium perenne.
AB  - The effects of growth-promoting hormone gibberellic acid 3 (GA3) on physiology,
      Pb phytoextraction, and metal detoxification mechanisms in Lolium perenne were
      studied. Results showed that addition of GA3 alone at lower doses (1 or 10 MUM)
      facilitated antioxidant defense of L. perenne under Pb stress, decreased the
      toxicity of Pb in plant shoot by increasing the proportion of Pb in cell wall,
      hence significantly enhanced photosynthesis and plant growth, as well as Pb
      uptake and accumulation in L. perenne (P < 0.05). However, these indicators
      showed the opposite changes when treated with GA3 at a higher dose (100 MUM). Of
      the total Pb in plant shoot, 36-51% was associated with cell wall, and 31-40% was
      soluble fraction, while 41.4-49.7% was NaCl extractable, 24.6-35.4% HAc
      extractable followed by other fractions. These findings suggest that Pb fixation
      by pectates and proteins in cell wall and sequestration in vacuole are
      responsible for Pb detoxification in plant, and the GA3 at 1 MUM appears to be
      optimal for enhancing Pb phytoextraction by L. perenne from Pb polluted soils. 

PMID- 25942520
TI  - Mast cell morphometry and densitometry in experimental skin wounds treated
      with a gel containing adelmidrol: a placebo controlled study.
AB  - The role of skin mast cells (MCs) in wound healing has been extensively
      investigated. The present study was designed to examine the effect of the
      aliamide adelmidrol on MCs during healing of experimental cutaneous wounds.
      Adelmidrol gel or the vehicle alone was applied 3 times daily on 5-mm punch
      biopsy wounds created on the thoracolumbar skin of 10 dogs. Wounds were allowed
      to heal by secondary intention. Eight-mm punch samples of the healing wounds were
      taken on days 1, 2, 4, 8, and 14, for histology. Mast cell numbers were counted
      and granular content assessed by densitometric analysis on toluidine blue-stained
      sections. The overall mean granule content was significantly greater in the
      treated wounds compared to control wounds, whereas no statistically significant
      differences in MC counts were observed. These data indicate a reduction in MC
      degranulation in wounds topically treated with adelmidrol suggesting that the
      compound is able to down-modulate skin MC releasability without affecting their
      number. 

PMID- 25942521
TI  - The Role of a Silver Releasing Lipido-colloid Contact Layer in Venous Leg
      Ulcers Presenting Inflammatory Signs Suggesting Heavy Bacterial Colonization:
      Results of a Randomized Controlled Study.
AB  - Objective. Clinical interest of silver in the management of chronic wounds is
      not fully established. The main objective of this clinical study was to assess
      the ability of a new silver releasing lipido-colloid contact layer to promote the
      healing process of venous leg ulcers (VLU) presenting inflammatory signs
      suggesting a heavy bacteria colonization and then a delayed healing, in
      comparison to the same wound dressing not impregnated with silver salts. METHODS:
      This was an open-labeled, randomized, controlled trial. VLU presenting at least 3
      out of 5 clinical signs suggesting heavy bacterial colonization were recruited.
      Patients were treated with contact layer silver dressing ([CLS], Restore(r)
      Contact Layer, Silver* (Hollister Wound Care, Libertyville, Ill) or contact layer
      dressing ([CL] Restore(r) Contact Layer**, Hollister Wound Care, Libertyville,
      Ill) for 4 weeks, then all treated ulcers were treated with CL for the 4
      additional weeks. Wound evaluation and area measurements were conducted weekly
      during the first 4 weeks and then at week 6 and 8. Main efficacy criterion was
      absolute wound area decrease (AD) at week 4 and week 8. RESULTS: Patients (N =
      102) were randomized and treated. Ulcers were present for nearly 11 months on
      average; 65% were recurrent and mean area was 20.0 +/- 17.8 cm2. Almost 80% of
      the treated VLU were stagnating/aggravating with their previous treatment. By
      week 4, mean surface area decreased by 6.5 +/- 13.4 cm2 (median: 4.2 cm2) and 1.3
      +/- 9.0 cm2 (median: 1.1 cm2) in CLS and CL groups, respectively (P = 0.023). At
      week 8, median decrease was 5.9 cm2 versus 0.8 cm2 (P = 0.002) with a wound
      percentage decrease of 47.9% and 5.6% (P = 0.036). Median closure rate was 0.145
      versus 0.044 cm2/day (P = 0.009) at week 4 and remained higher in the CLS group
      up to week 8 even after switching to CL dressing in these patients (P = 0.001).
      Odds ratio (multinomial logistic regression) of the chance to reach a >= 40%
      wound area reduction was 2.7 (95% CI: 1.1 to 6.7; P = 0.038) for silver treated
      ulcers. Dressing tolerance was good in both groups. CONCLUSION: A 4-week
      treatment with silver releasing lipido-colloid contact layer promotes a sustained
      increase of closure rate of venous leg ulcers presenting inflammatory signs
      suggesting a high bacterial load. Also marketed as *Urgotul(r) Silver and
      **Urgotul(r), Laboratoires Urgo, (France).   .

PMID- 25942522
TI  -  Assessment of a wound cleansing solution in the treatment of problem wounds.
AB  - Chronic wounds will heal in most cases if provided an optimal local wound
      environment and therapy that addresses underlying disease. The quality of topical
      wound management will influence the speed of the wound healing process. The value
      of cleansing chronic wounds is considered a basic principle in modern wound
      management. Several methods are available for wound cleansing and debridement.
      Currently, there has been focus on measures of wound cleansing whereby debris and
      exudate are gently and continuously removed to prepare the wound bed for wound
      closure. For this purpose, physiological solutions or specific disinfectants may
      be used. This retrospective analysis of existing data was performed looking at
      the clinical efficacy and cost-effectiveness of using a wound antiseptic to treat
      problem wounds. Wound cleansing upon dressing changes using a polyhexanide
      containing solution (Prontosan(r), B Braun, Melsungen AG, Germany) in venous leg
      ulcers was compared to cleansing with either Ringer's solution or saline. The
      wounds of the patients treated with polyhexanide solution healed faster and in
      more cases (97% versus 89%). The Kaplan-Meier mean estimate (and associated
      standard error [SE]) demonstrated a statistically significant difference between
      treatment groups (P < 0.0001) in time to healing. The Kaplan-Meier mean time to
      healing for the study group (SG) was 3.31 months (SE = 0.17) compared to 4.42
      months (SE = 0.19) for the control group ([CG], saline/Ringer's solution).  . 

PMID- 25942523
TI  - The Japanese pressure ulcer surveillance study: a retrospective cohort study
      to determine prevalence of pressure ulcers in Japanese hospitals.
AB  - Aim. To evaluate the governmental regulation system introduced in October
      2002 by investigating the prevalence of pressure ulcers (PUs) and to investigate
      the relationship between the change in prevalence and the structure and system
      within hospitals. METHODS: This retrospective cohort study used 2582 randomly
      sampled hospitals in Japan. Questionnaires were mailed to each type of hospital,
      including university hospitals, acute hospitals, acute and long-term (mixed care)
      hospitals, long-term care hospitals, and psychiatric hospitals. Prevalence and
      severity of pressure ulcers over 4 consecutive periods (1 month before the
      introduction of regulation, immediately after the introduction, 6 months later,
      and 1 year later) and related factors for the improved prevalence were assessed.
      RESULTS: The overall prevalence before the regulation was 4.26%, which decreased
      to 4.18% immediately after regulation, and to 3.95% and 3.64% 6 months and 1 year
      later, respectively. The overall proportion of Stage III and IV pressure ulcers
      acquired after admission was 23.9% and 10.9%, respectively, before introduction
      of regulation, and gradually decreased to 18.8% and 8.1%, respectively, after 1
      year. The related factor for improved PU prevalence was sufficient distribution
      of alternating air mattresses (odds ratio = 2.259, 95% CI; 1.091-4.679, P =
      0.028). CONCLUSION: The governmental regulation had a clinically important effect
      on the decrease in PU prevalence. The regulation focused on the structure of
      hospitals was confirmed to influence the outcome of hospital care quality.

PMID- 25942524
TI  - Prevention of projectile and aerosol contamination during pulsatile lavage
      irrigation using a wound irrigation bag  .
AB  - Pulsatile lavage is a high-pressure irrigation treatment commonly used in the
      debridement of wounds. The risk of exposure to bloodborne pathogens and
      contaminants using high-pressure irrigation has been well documented in the
      literature. Projectile droplets and aerosolized fine droplets may form and
      spread, potentially contaminating the treatment facility and infecting personnel.
      A new device (Wound Irrigation Bag(c), Pulse Care Medical LLC, North Andover,
      Mass) has been designed to decrease the dissemination of projectile and
      aerosolized particles. The wound irrigation bag (WIB) uses containment to
      decrease the amount of projectile and aerosolized pathogens spread during
      pulsatile lavage. This randomized prospective trial demonstrated that the WIB
      significantly decreased the amount of bacterial colony forming units disseminated
      during pulsatile lavage of infected wounds compared to standard wound irrigation
      techniques. The WIB is a useful new tool in the armamentarium of wound care that
      protects the debridement facility and the personnel who operate it by
      significantly reducing the dissemination of infectious particles. 

PMID- 25942525
TI  - Clinical trial transparency update: an assessment of the disclosure of results of
      company-sponsored trials associated with new medicines approved in Europe in
      2012.
AB  - BACKGROUND: The objective of this study was to assess the timely disclosure of
      results of company-sponsored clinical trials related to all new medicines
      approved by the European Medicines Agency (EMA) during 2012. This is an extension
      of the previously reported study of trials related to all new medicines approved
      in Europe in 2009, 2010 and 2011, which found that over three-quarters of all
      these trials were disclosed within 12 months and almost 90% were disclosed by the
      end of the study. METHODS: The methodology used was exactly as previously
      reported. Various publicly available information sources were searched for both
      clinical trial registration and disclosure of results. All completed company
      sponsored trials related to each new medicine approved for marketing by the EMA
      in 2012, carried out in patients and recorded on a clinical trials registry
      and/or included in an EMA European Public Assessment Report (EPAR), were
      included. Information sources were searched between 1 May and 31 July 2014.
      OUTCOME MEASURES AND RESULTS: The main outcome measure was the proportion of
      trials for which results had been disclosed on a registry or in the scientific
      literature either within 12 months of the later of either first regulatory
      approval or trial completion, or by 31 July 2014 (end of survey). Of the
      completed trials associated with 23 new medicines licensed to 17 different
      companies in 2012, results of 90% (307/340) had been disclosed within 12 months,
      and results of 92% (312/340) had been disclosed by 31 July 2014. CONCLUSIONS: The
      disclosure rate within 12 months of 90% suggests the industry is now achieving
      disclosure in a timely manner more consistently than before. The overall
      disclosure rate at study end of 92% indicates that the improvement in
      transparency amongst company-sponsored trials has been maintained in the trials
      associated with new medicines approved in 2012.

PMID- 25942526
TI  - 3-D gaming environment preferences: Inversion of the Y-axis.
AB  - Differences between preference groups based on the control scheme of the Y-axis
      or pitch (either default or inverted) in 3-D gaming were explored both with
      measures of pre-existing traits, as well as reactions to a short gaming session.
      Participants who preferred to invert the Y-axis controls showed significantly
      greater overall tendency for immersion than the non-inverters. Similarly, the
      participants who inverted the Y-axis also reported significantly higher levels of
      presence in the gaming task than the non-inverter. Finally, when participants'
      controls in the gaming task were mismatched to their preference, they exhibited
      significantly higher perceived workload in the gaming task. Implications of these
      findings focus on determining a basis for differences in the population, and how
      these differences may impact spatial reasoning and task-specific training,
      especially in aviation. PRACTITIONER SUMMARY: Differing preferences for
      controlling a user's visual perspective in a three-dimensional virtual
      environment were shown to exist in the population, with indications of increased
      workload when randomly assigned to use a non-preferred control scheme. These
      control preferences showed evidence of association with the user's tendency for
      immersion in virtual environments.

PMID- 25942527
TI  - Voltammetric Scanning Electrochemical Cell Microscopy: Dynamic Imaging of
      Hydrazine Electro-oxidation on Platinum Electrodes.
AB  - Voltammetric scanning electrochemical cell microscopy (SECCM) incorporates cyclic
      voltammetry measurements in the SECCM imaging protocol, by recording
      electrochemical currents in a wide potential window at each pixel in a map. This
      provides much more information compared to traditional fixed potential imaging.
      Data can be represented as movies (hundreds of frames) of current (over a surface
      region) at a series of potentials and are highly revealing of subtle variations
      in electrode activity. Furthermore, by combining SECCM data with other forms of
      microscopy, e.g. scanning electron microscopy and electron backscatter
      diffraction data, it is possible to directly relate the current-voltage
      characteristics to spatial position and surface structure. In this work we use a
      "hopping mode", where the SECCM pipet probe is translated toward the surface at a
      series of positions until meniscus contact. Small amounts of residue left on the
      surface, upon probe retraction, demark the precise area of each measurement. We
      use these techniques to study hydrazine oxidation on a polycrystalline platinum
      substrate both in air and in a deaerated environment. In both cases, the detected
      faradaic current shows a structural dependence on the surface crystallographic
      orientation. Significantly, in the presence of oxygen (aerated solution) the
      electrochemical current decreases strongly for almost all grains
      (crystallographic orientations). The results highlight the flexibility of
      voltammetric SECCM for electrochemical imaging and present important implications
      for hydrazine electroanalysis. 

PMID- 25942528
TI  - Cell-specific gene promoters are marked by broader spans of H3K4me3 and are
      associated with robust gene expression patterns.

PMID- 25942529
TI  - Technological advances in epigenomics lead to a better understanding of
      inflammatory diseases, decitabine and H3K27me3.

PMID- 25942530
TI  - The role of epigenomics in the neurodegeneration of ataxia-telangiectasia.

PMID- 25942531
TI  - Application of artificial neural networks to link genetic and environmental
      factors to DNA methylation in colorectal cancer.
AB  - AIMS: We applied artificial neural networks (ANNs) to understand the connections
      among polymorphisms of genes involved in folate metabolism, clinico-pathological
      features and promoter methylation levels of MLH1, APC, CDKN2A(INK4A), MGMT and
      RASSF1A in 83 sporadic colorectal cancer (CRC) tissues, and to link dietary and
      lifestyle factors with gene promoter methylation. MATERIALS & METHODS: Promoter
      methylation was assessed by means of methylation-sensitive high-resolution
      melting and genotyping by PCR-RFLP technique. Data were analyzed with the Auto
      Contractive Map, a special kind of ANN able to define the strength of the
      association of each variable with all the others and to visually show the map of
      the main connections. RESULTS: We observed a strong connection between the low
      methylation levels of the five CRC genes and the MTR 2756AA genotype. Several
      other connections were revealed, including those between dietary and lifestyle
      factors and the methylation levels of CRC genes. CONCLUSION: ANNs revealed the
      complexity of the interconnections among factors linked to DNA methylation in
      CRC.

PMID- 25942532
TI  - Epigenetic therapy for solid tumors: from bench science to clinical trials.
AB  - The cancer epigenome is characterized by global DNA methylation and chromatin
      changes, such as the hypermethylation of specific CpG island promoters.
      Epigenetic agents like DNA methyltransferase or histone deacetylase inhibitors
      induce phenotype changes by reactivation of epigenetically silenced tumor
      suppressor genes. Despite initial promise in hematologic malignancies, epigenetic
      agents have not shown significant efficacy as monotherapy against solid tumors.
      Recent trials showed that epigenetic agents exert favorable modifier effects when
      combined with chemotherapy, hormonal therapy, or other epigenetic agents. Due to
      the novel nature of their mechanism, it is important to reconsider the optimal
      patient selection, drug regimen, study design, and outcome measures when pursuing
      future trials in order to discover the full potential of this new therapeutic
      modality. 

PMID- 25942534
TI  - Genetic alterations of DNA methylation machinery in human diseases.
AB  - DNA methylation plays a critical role in the regulation of chromatin structure
      and gene expression and is involved in a variety of biological processes. The
      levels and patterns of DNA methylation are regulated by both DNA
      methyltransferases (DNMT1, DNMT3A and DNMT3B) and 'demethylating' proteins,
      including the ten-eleven translocation (TET) family of dioxygenases (TET1, TET2
      and TET3). The effects of DNA methylation on chromatin and gene expression are
      largely mediated by methylated DNA 'reader' proteins, including MeCP2. Numerous
      mutations in DNMTs, TETs and MeCP2 have been identified in cancer and
      developmental disorders, highlighting the importance of the DNA methylation
      machinery in human development and physiology. In this review, we describe these
      mutations and discuss how they may lead to disease phenotypes. 

PMID- 25942533
TI  - Epigenetic regulation of chronic pain.
AB  - Chronic pain arising from peripheral inflammation and tissue or nerve injury is a
      common clinical symptom. Although intensive research on the neurobiological
      mechanisms of chronic pain has been carried out during previous decades, this
      disorder is still poorly managed by current drugs such as opioids and
      nonsteroidal anti-inflammatory drugs. Inflammation, tissue injury and/or nerve
      injury-induced changes in gene expression in sensory neurons of the dorsal root
      ganglion, spinal cord dorsal horn and pain-associated brain regions are thought
      to participate in chronic pain genesis; however, how these changes occur is still
      elusive. Epigenetic modifications including DNA methylation and covalent histone
      modifications control gene expression. Recent studies have shown that peripheral
      noxious stimulation changes DNA methylation and histone modifications and that
      these changes may be related to the induction of pain hypersensitivity under
      chronic pain conditions. This review summarizes the current knowledge and
      progress in epigenetic research in chronic pain and discusses the potential role
      of epigenetic modifications as therapeutic antinociceptive targets in this
      disorder. 

PMID- 25942535
TI  - Acinar cell reprogramming: a clinically important target in pancreatic disease.
AB  - Acinar cells of the pancreas produce the majority of enzymes required for
      digestion and make up >90% of the cells within the pancreas. Due to a common
      developmental origin and the plastic nature of the acinar cell phenotype, these
      cells have been identified as a possible source of beta cells as a therapeutic
      option for Type I diabetes. However, recent evidence indicates that acinar cells
      are the main source of pancreatic intraepithelial neoplasias (PanINs), the
      predecessor of pancreatic ductal adenocarcinoma (PDAC). The conversion of acinar
      cells to either beta cells or precursors to PDAC is dependent on reprogramming of
      the cells to a more primitive, progenitor-like phenotype, which involves changes
      in transcription factor expression and activity, and changes in their epigenetic
      program. This review will focus on the mechanisms that promote acinar cell
      reprogramming, as well as the factors that may affect these mechanisms. 

PMID- 25942536
TI  - Oxidative stress and DNA methylation regulation in the metabolic syndrome.
AB  - DNA methylation is implicated in tissue-specific gene expression and genomic
      imprinting. It is modulated by environmental factors, especially nutrition.
      Modified DNA methylation patterns may contribute to health problems and
      susceptibility to complex diseases. Current advances have suggested that the
      metabolic syndrome (MS) is a programmable disease, which is characterized by
      epigenetic modifications of vital genes when exposed to oxidative stress.
      Therefore, the main objective of this paper is to critically review the central
      context of MS while presenting the most recent knowledge related to epigenetic
      alterations that are promoted by oxidative stress. Potential pro-oxidant
      mechanisms that orchestrate changes in methylation profiling and are related to
      obesity, diabetes and hypertension are discussed. It is anticipated that the
      identification and understanding of the role of DNA methylation marks could be
      used to uncover early predictors and define drugs or diet-related treatments able
      to delay or reverse epigenetic changes, thereby combating MS burden. 

PMID- 25942537
TI  - Epigenetic modifiers in normal and malignant hematopoiesis.
AB  - Genome scale sequencing in patients with cancer has revealed a lower frequency of
      genetic aberrations in hematologic disorders compared with most other
      malignancies, suggesting a prominent role for epigenetic mechanisms. In parallel,
      epigenetic modifiers that are altered in cancer play critical roles in normal
      hematopoietic development, influencing both self-renewal of hematopoietic stem
      cells and differentiation into the different lineages. In this review, we aim to
      compare the role of several key DNA or histone modifying enzymes and complexes in
      normal development and hematopoietic malignancies, including DNMT3A, TET2, IDH1,
      IDH2, MLL1, MLL4, DOT1L, PRC1/2 and WSHC1/NSD2/MMSET. Insights into their
      biological mechanisms led to the development of therapies designed to target
      mutant IDH1 and IDH2, DOT1L in MLL-rearranged leukemias and EZH2 in several
      cancer types including lymphomas. Inhibitors for these enzymes are currently in
      clinical trials. 

PMID- 25942539
TI  - Corrigendum.

PMID- 25942538
TI  - Histone methylations in heart development, congenital and adult heart diseases.
AB  - Heart development comprises myocyte specification, differentiation and cardiac
      morphogenesis. These processes are regulated by a group of core cardiac
      transcription factors in a coordinated temporal and spatial manner. Histone
      methylation is an emerging epigenetic mechanism for regulating gene
      transcription. Interplay among cardiac transcription factors and histone lysine
      modifiers plays important role in heart development. Aberrant expression and
      mutation of the histone lysine modifiers during development and in adult life can
      cause either embryonic lethality or congenital heart diseases, and influences the
      response of adult hearts to pathological stresses. In this review, we describe
      current body of literature on the role of several common histone methylations and
      their modifying enzymes in heart development, congenital and adult heart
      diseases. 

PMID- 25942540
TI  - Multi-domain short peptide molecules for in situ synthesis and
      biofunctionalization of gold nanoparticles for integrin-targeted cell uptake.
AB  - We describe design and synthesis model of multidomain (modular) peptides (MDPs),
      which direct a reaction cascade coupling the synthesis and surface
      functionalization of gold nanoparticles (AuNPs) in a single step. The synthesis
      is achieved via simple mixing of the aqueous solutions of auric acid and MDPs at
      room temperature without the addition of any surfactants or toxic intermediate
      reagents. This method allows facile control over the nanoparticle size between ~2
      15 nm, which opens a practical window for biomedical applications. In contrast to
      the conventional citrate-mediated methods, peptide-mediated synthesis and
      stabilization provide increased colloidal stability to AuNPs. As a proof of this
      concept, we demonstrate active targeting of human breast adenocarcinoma cell line
      (MCF7) using the one-step-prepared engineered AuNPs. Overall, we propose a single
      step, chemically greener, biologically safer method for the synthesis and surface
      functionalization of gold nanoparticles in a size-controlled manner. The chemical
      versatility of the MDP design broadens the applicability of this strategy,
      thereby emerging as a successful alternative for the currently available
      nanoparticle preparation technologies. 

PMID- 25942541
TI  - Experimental mixture design as a tool for the synthesis of antimicrobial
      selective molecularly imprinted monodisperse microbeads.
AB  - The effect of the cross-linker on the shape and size of molecular imprinted
      polymer (MIP) beads prepared by precipitation polymerization has been evaluated
      using a chemometric approach. Molecularly imprinted microspheres for the
      selective recognition of fluoroquinolone antimicrobials were prepared in a one
      step precipitation polymerization procedure using enrofloxacin (ENR) as the
      template molecule, methacrylic acid as functional monomer, 2-hydroxyethyl
      methacrylate as hydrophilic comonomer, and acetonitrile as the porogen. The type
      and amount of cross-linker, namely ethylene glycol dimethacrylate, divinylbenzene
      or trimethylolpropane trimethacrylate, to obtain monodispersed MIP spherical
      beads in the micrometer range was optimized using a simplex lattice design.
      Particle size and morphology were assessed by scanning electron microscopy,
      dynamic light scattering, and nitrogen adsorption measurements. Electron
      paramagnetic resonance spectroscopy in conjunction with a nitroxide as spin probe
      revealed information about the microviscosity and polarity of the binding sites
      in imprinted and nonimprinted polymer beads. 

PMID- 25942542
TI  - Aposematism.

PMID- 25942543
TI  - Deaf white cats.

PMID- 25942544
TI  - Polyploidy.
AB  - Polyploidy is defined as an increase in genome DNA content. Throughout the plant
      and animal kingdoms specific cell types become polyploid as part of their
      differentiation programs. When this occurs in subsets of tissues within an
      organism it is termed somatic polyploidy, because it is distinct from the
      increase in ploidy that is inherited through the germline and present in every
      cell type of the organism. Germline polyploidy is common in plants and occurs in
      some animals, such as amphibians, but will not be discussed further here. Somatic
      polyploid cells can be mononucleate or multinucleate, and the replicated sister
      chromatids can remain attached and aligned, producing polytene chromosomes, or
      they can be dispersed (Figure 1). In this Primer, we focus on why somatic
      polyploidy occurs and how cells become polyploid - the first of these issues
      being more speculative, given the status of the field.

PMID- 25942545
TI  - Immediate susceptibility to visual illusions after sight onset.
AB  - The dominant accounts of many visual illusions are based on experience-driven
      development of sensitivity to certain visual cues. According to such accounts,
      learned associations between observed two-dimensional cues (say, converging
      lines) and the real three-dimensional structures they represent (a surface
      receding in depth) render us susceptible to misperceiving some images that are
      cleverly contrived to contain those two-dimensional cues. While this explanation
      appears reasonable, it lacks direct experimental validation. To contrast it with
      an account that dispenses with the need for visual experience, it is necessary to
      determine whether susceptibility to the illusion is present immediately after
      birth; however, eliciting reliable responses from newborns is fraught with
      operational difficulties, and studies with older infants are incapable of
      resolving this issue. Our work with children who gain sight after extended early
      onset blindness, as part of Project Prakash, provides a potential way forward. We
      report here that the newly sighted children, ranging in age from 8 through 16
      years, exhibit susceptibility to two well-known geometrical visual illusions,
      Ponzo [1] and Muller-Lyer [2], immediately after the onset of sight. This finding
      has implications not only for the likely explanations of these illusions, but
      more generally, for the nature-nurture argument as it relates to some key aspects
      of visual processing. 

PMID- 25942546
TI  - Stretchy nerves are an essential component of the extreme feeding mechanism of
      rorqual whales.
AB  - Rorqual whales (Balaenopteridae) are among the largest vertebrates that have ever
      lived and include blue (Balaenoptera musculus) and fin (Balaenoptera physalus)
      whales. Rorquals differ from other baleen whales (Mysticeti) in possessing
      longitudinal furrows or grooves in the ventral skin that extend from the mouth to
      the umbilicus. This ventral grooved blubber directly relates to their
      intermittent lunge feeding strategy, which is unique among vertebrates and was
      potentially an evolutionary innovation that led to gigantism in this lineage [1].
      This strategy involves the rorqual whale rapidly engulfing a huge volume of prey
      laden water and then concentrating the prey by more slowly expelling the water
      through baleen plates (Figure 1A). The volume of water engulfed during a lunge
      can exceed the volume of the whale itself [2]. During engulfment, the whale
      accelerates, opens its jaw until it is almost perpendicular to the rostrum, and
      then the highly compliant floor of the oral cavity is inflated by the incoming
      water [3]. The floor of the oral cavity expands by inversion of the tongue and
      ballooning of the adjacent floor of the mouth into the cavum ventrale, an immense
      fascial pocket between the body wall and overlying blubber layer that reaches as
      far back as the umbilicus. The ventral grooved blubber in fin whales expands by
      an estimated 162% in the circumferential direction and 38% longitudinally [4]. In
      fin whales, multiple lunges can occur during a single dive, and the average time
      between lunges is just over forty seconds [3]. Here, we show that nerves in the
      floor of the oral cavity of fin whales are highly extensible. 

PMID- 25942547
TI  - Spatial representation: maps of fragmented space.
AB  - Grid cells in medial entorhinal cortex are thought to act as a neural metric for
      spatial navigation. A new study has examined the ability of grid cells to use
      self-motion cues to form a global map across fragmented spaces. 

PMID- 25942548
TI  - Cytokinesis: does Mid1 have an identity crisis?
AB  - New work shows the anillin-related protein Mid1 does not position the cytokinetic
      ring in the fission yeast Schizosaccharomyces japonicus, unlike its role in S.
      pombe. Further analysis suggests the conserved function of Mid1-like anillin
      proteins may be in scaffolding, not positioning, the cytokinetic ring. 

PMID- 25942549
TI  - Octopus movement: push right, go left.
AB  - Octopus arms have essentially infinite degrees of freedom. New research shows
      that, despite this potentially great complexity, to locomote octopuses simply
      elongate one or more arms, thus pushing the body in the opposite direction, and
      do so without activating the arms in an ordered pattern. 

PMID- 25942550
TI  - Biodiversity: the known, unknown, and rates of extinction.
AB  - How many species are there and how many have we lost? New estimates shed light on
      this question in the marine realm. 

PMID- 25942551
TI  - Planar polarity: converting a morphogen gradient into cellular polarity.
AB  - Epithelial cells are polarized within the apico-basal and planar axes. The latter
      - planar cell polarity - requires long-range regulation of orientation as well as
      short-range, cell-to-cell realignment through feedback loops. New insights into
      the long-range, gradient-type regulation reveal how a kinase translates the
      morphogen gradient input into cellular orientation. 

PMID- 25942552
TI  - Neural coding: time contraction and dilation in the striatum.
AB  - How the brain encodes time is poorly understood. New research on rats provides
      evidence that striatal neurons encode time, and that the code can dilate or
      contract to time different intervals. 

PMID- 25942553
TI  - Cell division: stem cells take the stage.
AB  - A pool of proliferating germline stem cells is essential for gamete production in
      Caenorhabditis elegans. A new study applies sophisticated live imaging to assess
      mitotic progression and cell cycle control in these cells, yielding new insights
      into stem cell division. 

PMID- 25942554
TI  - Social evolution: slimy cheats pay a price.
AB  - Variation in the routes to social success has led to the designation of 'cheats'
      and 'cooperators', but new work shows that selection on non-social traits can
      give the illusion of social cheating in the social amoeba Dictyostelium
      discoideum. 

PMID- 25942555
TI  - Human gustation: when the brain has taste.
AB  - What we put into our mouths can nourish or kill us. A new study uses state-of-the
      art electroencephalogram decoding to detail how we and our brains know what we
      taste. 

PMID- 25942556
TI  - Plant phototropic growth.
AB  - Plants are photoautotrophic sessile organisms that use environmental cues to
      optimize multiple facets of growth and development. A classic example is
      phototropism - in shoots this is typically positive, leading to growth towards
      the light, while roots frequently show negative phototropism triggering growth
      away from the light. Shoot phototropism optimizes light capture of leaves in low
      light environments and hence increases photosynthetic productivity. Phototropins
      are plasma-membrane-associated UV-A/blue-light activated kinases that trigger
      phototropic growth. Light perception liberates their protein kinase domain from
      the inhibitory action of the amino-terminal photosensory portion of the
      photoreceptor. Following a series of still poorly understood events, phototropin
      activation leads to the formation of a gradient of the growth hormone auxin
      across the photo-stimulated stem. The greater auxin concentration on the shaded
      compared with the lit side of the stem enables growth reorientation towards the
      light. In this Minireview, we briefly summarize the signaling steps starting from
      photoreceptor activation until the establishment of a lateral auxin gradient,
      ultimately leading to phototropic growth in shoots. 

PMID- 25942557
TI  - New method for the determination of parabens and bisphenol A in human milk
      samples using ultrasound-assisted extraction and clean-up with dispersive
      sorbents prior to UHPLC-MS/MS analysis.
AB  - A sensitive and accurate analytical method for the determination of methyl-,
      ethyl-, propyl- and butylparaben and bisphenol A in human milk samples has been
      developed and validated. The combination of ultrasound-assisted extraction (UAE)
      and a simplified and rapid clean-up technique that uses sorbent materials has
      been successfully applied for the preparation of samples prior to ultra-high
      performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS)
      analysis. The analytes were extracted from freeze-dried human milk samples using
      acetonitrile and ultrasonic radiation (three 15-min cycles at 70% amplitude), and
      further cleaned-up with C18 sorbents. The most influential parameters affecting
      the UAE method and the clean-up steps were optimized using design of experiments.
      Negative electrospray ionization (ESI) in the selected reaction monitoring (SRM)
      mode was used for MS detection. The use of two reactions for each compound
      allowed simultaneous quantification and identification in one run. The analytes
      were separated in less than 10min. Deuterium-labeled ethylparaben-d5 (EPB-d5) and
      deuterium-labeled bisphenol A-d16 (BPA-d16) were used as surrogates. The limits
      of quantification ranged from 0.4 to 0.7ngmL(-1), while inter- and intra-day
      variability was under 11.1% in all cases. In the absence of certified reference
      materials, recovery assays with spiked samples using matrix-matched calibration
      were used to validate the method. Recovery rates ranged from 93.8% to 112.2%. The
      proposed method was satisfactorily applied for the determination of four selected
      parabens and bisphenol A in human milk samples obtained from nursing mothers
      living in the province of Granada (Spain). 

PMID- 25942558
TI  - A New Technique for Making the Aberdeen Knot in Laparoscopic Surgery.
AB  - INTRODUCTION: Laparoscopic knot-tying is an advanced skill. The traditional
      square knot or surgeon's knot is often used at the end of a continuous suture
      line in laparoscopic surgery. The Aberdeen knot has been shown to be stronger and
      more secure than the surgeon's knot for ending a suture line but is rarely used
      in laparoscopic surgery. We have developed a new technique to make the Aberdeen
      knot laparoscopically. MATERIALS AND METHODS: At the end of a continuous suture
      line, the needle-attached end of the suture is held with a right-handed
      instrument and passed through the instrument into the loop of the last suture.
      The left-handed instrument is passed through the triangle made by the inserted
      suture, the right-handed instrument, and the loop through which the suture is
      inserted. The suture held by the right-handed instrument is then pulled, closing
      that loop and creating a new one on the left-handed instrument. The right-handed
      instrument is passed into the loop, and the same technique is then repeated two
      or more times. To finish the knot, the needle-attached end is passed through the
      loop, and the knot is tied. DISCUSSION AND CONCLUSIONS: Laparoscopic suturing and
      knotting are difficult, particularly in single-port laparoscopic surgery, where
      the angle between working instruments is narrow. Furthermore, knotting the end of
      a continuous suture is difficult when the thread becomes short. In all of these
      situations, this technique is able to facilitate and simplify knot-tying. No
      special instruments are required to make a "laparoscopic Aberdeen knot."

PMID- 25942559
TI  - The Impact of Combat Status on Veterans' Attitudes Toward Help Seeking: The
      Hierarchy of Combat Elitism.
AB  - Many veterans do not seek assistance for mental health concerns despite the
      staggering prevalence of trauma-related symptomatology. Barriers to service
      provision include personal and professional stigma and inter-veteran attitudes
      that dictate who is more or less deserving of services. Veteran attitudes are
      shaped by military culture, which promotes a hyper-masculine paradigm upholding
      combat experience as the defining feature of the "ideal soldier." The
      stratification of soldiers into combat or non-combat status creates a hierarchy
      of combat elitism that extends far beyond active duty. This pilot study surveyed
      veterans (n = 24) to explore how combat experience may affect attitudes toward
      help seeking. Findings indicate combat and non-combat veterans are less accepting
      of non-combat veterans' help-seeking behavior, supporting the notion that
      veterans' attitudes toward help seeking are influenced by combat status. Despite
      limitations, the results of this study reflect a need for increased attention to
      the attitudes veterans have about each other and themselves. 

PMID- 25942560
TI  - Tuning the Magnetic Anisotropy of Single Molecules.
AB  - The magnetism of single atoms and molecules is governed by the atomic scale
      environment. In general, the reduced symmetry of the surrounding splits the d
      states and aligns the magnetic moment along certain favorable directions. Here,
      we show that we can reversibly modify the magnetocrystalline anisotropy by
      manipulating the environment of single iron(II) porphyrin molecules adsorbed on
      Pb(111) with the tip of a scanning tunneling microscope. When we decrease the tip
      molecule distance, we first observe a small increase followed by an exponential
      decrease of the axial anisotropy on the molecules. This is in contrast to the
      monotonous increase observed earlier for the same molecule with an additional
      axial Cl ligand ( Nat. Phys. 2013 , 9 , 765 ). We ascribe the changes in the
      anisotropy of both species to a deformation of the molecules in the presence of
      the attractive force of the tip, which leads to a change in the d level
      alignment. These experiments demonstrate the feasibility of a precise tuning of
      the magnetic anisotropy of an individual molecule by mechanical control. 

PMID- 25942562
TI  - Bioeconomic analysis of the environmental impact of a marine fish farm.
AB  - The evaluation of the environmental impact of aquaculture installations is
      nowadays a common social demand in many countries. The usual scientific approach
      to this question has been to assess the outcome from an ecological perspective,
      focussing on the effects produced on benthos or the water column and interactions
      with marine flora and fauna. In this paper, a bioeconomic model is developed to
      extend this traditional approach, to determine both the amount of total settled
      matter, its dispersion on the ocean floor and impacts on the marine ecosystem,
      while also taking into account other social considerations such as discounted net
      profits and investment returns. The model was applied to the case of off-shore
      gilthead seabream production in a coastal area of the Canary Isles archipelago,
      where the tidal current is predominant. Cage emissions and the degree of
      degradation of seagrass meadows on the seabed were taken as ecological impact
      indicators, while the net present value (NPV) for a specific time period was used
      as an economic indicator. By analysing the simulation results obtained by the
      bioeconomic model, we were able to determine the combination of production volume
      and harvest quantity which yields the greatest economic efficiency for different
      levels of degraded area. 

PMID- 25942561
TI  - Apolipoprotein B48, the Structural Component of Chylomicrons, Is Sufficient to
      Antagonize Staphylococcus aureus Quorum-Sensing.
AB  - Serum lipoproteins (LP) are increasingly being recognized as dual purpose
      molecules that contribute to both cholesterol homeostasis and host innate
      defense. In fact, very low LP levels are associated with increased risk of
      bacterial infection in critically ill patients. In this respect, we reported that
      apolipoprotein B100 (apoB100), the 4536 amino acid structural protein of very low
      density lipoprotein (VLDL) produced by the liver, limits Staphylococcus aureus
      pathogenesis. S. aureus uses quorum-sensing (QS) via the accessory gene regulator
      (agr) operon and an autoinducing peptide (AIP) to coordinate expression of over
      200 virulence genes. ApoB100 prevents agr activation by binding and sequestering
      secreted AIP. Importantly, human serum LP are produced not only by the liver, but
      are also produced by enterocytes, in the form of chylomicrons, during uptake of
      dietary lipids. In contrast to apoB100 in VLDL, human enterocytes use apoB48, the
      N-terminal 2152 amino acids (48%) of apoB100, as the structural component of
      chylomicrons. Interestingly, enteral feeding of critically ill patients has been
      associated with decreased risk of infectious complications, suggesting
      chylomicrons could contribute to host innate defense in critically ill patients
      when serum LP production by the liver is limited during the acute phase response.
      Therefore, we hypothesized that apoB48 would be sufficient to antagonize S.
      aureus QS. As expected, isolated apoB48-LP bound immobilized AIP and antagonized
      agr-signaling. ApoB48- and apoB100-LP inhibited agr activation with IC50s of 3.5
      and 2.3 nM, respectively, demonstrating a conserved AIP binding site.
      Importantly, apoB48-LP antagonized QS, limited morbidity and promoted bacterial
      clearance in a mouse model of S. aureus infection. This work demonstrates that
      both naturally occurring forms of apolipoprotein B can antagonize S. aureus QS,
      and may suggest a previously unrecognized role for chylomicrons and enterocytes
      in host innate defense against S. aureus QS-mediated pathogenesis. 

PMID- 25942563
TI  - NMDA Receptor Antagonist Attenuates Bleomycin-Induced Acute Lung Injury.
AB  - BACKGROUND: Glutamate is a major neurotransmitter in the central nervous system
      (CNS). Large amount of glutamate can overstimulate N-methyl-D-aspartate receptor
      (NMDAR), causing neuronal injury and death. Recently, NMDAR has been reported to
      be found in the lungs. The aim of this study is to examine the effects of
      memantine, a NMDAR channel blocker, on bleomycin-induced lung injury mice.
      METHODS: C57BL/6 mice were intratracheally injected with bleomycin (BLM) to
      induce lung injury. Mice were randomized to receive saline, memantine (Me), BLM,
      BLM plus Me. Lungs and BALF were harvested on day 3 or 7 for further evaluation.
      RESULTS: BLM caused leukocyte infiltration, pulmonary edema and increase in
      cytokines, and imposed significant oxidative stress (MDA as a marker) in lungs.
      Memantine significantly mitigated the oxidative stress, lung inflammatory
      response and acute lung injury caused by BLM. Moreover, activation of NMDAR
      enhances CD11b expression on neutrophils. CONCLUSIONS: Memantine mitigates
      oxidative stress, lung inflammatory response and acute lung injury in BLM
      challenged mice.

PMID- 25942564
TI  - Resveratrol antibacterial activity against Escherichia coli is mediated by Z-ring
      formation inhibition via suppression of FtsZ expression.
AB  - Resveratrol exhibits a potent antimicrobial activity. However, the mechanism
      underlying its antibacterial activity has not been shown. In this study, the
      antibacterial mechanism of resveratrol was investigated. To investigate induction
      of the SOS response, a strain containing the lacZ+gene under the control of an
      SOS-inducible sulA promoter was constructed. DNA damage was measured by pulse
      field gel electrophoresis (PFGE). After resveratrol treatment, the cells were
      observed by confocal microscopy. For the RNA silencing assay, ftsZ-specific
      antisense peptide nucleic acid (PNA) was used. Reactive oxygen species (ROS)
      production increased in Escherichia coli after resveratrol treatment; however,
      cell growth was not recovered by ROS quenching, indicating that, in this
      experiment, ROS formation and cell death following resveratrol treatment were not
      directly correlated. Resveratrol treatment increased DNA fragmentation in cells,
      while SOS response-related gene expression levels increased in a dose-dependent
      manner. Cell elongation was observed after resveratrol treatment. Elongation was
      induced by inhibiting FtsZ, an essential cell-division protein in prokaryotes,
      and resulted in significant inhibition of Z-ring the formation in E. coli. The
      expression of ftsZ mRNA was suppressed by resveratrol. Our results indicate that
      resveratrol inhibits bacterial cell growth by suppressing FtsZ expression and Z
      ring formation.

PMID- 25942565
TI  - Improvement of Omega-3 Docosahexaenoic Acid Production by Marine Dinoflagellate
      Crypthecodinium cohnii Using Rapeseed Meal Hydrolysate and Waste Molasses as
      Feedstock.
AB  - Rapeseed meal and waste molasses are two important agro-industrial by-products
      which are produced in large quantities. In this study, solid state fermentation
      and fungal autolysis were performed to produce rapeseed meal hydrolysate (RMH)
      using fungal strains of Aspergillus oryzae, Penicillium oxalicum and Neurospora
      crassa. The hydrolysate was used as fermentation feedstock for heterotrophic
      growth of microalga Crypthecodinium cohnii that produce docosahexaenoic acid
      (DHA). The addition of waste molasses as a supplementary carbon source greatly
      increased the biomass and DHA yield. In the batch fermentations using media
      composed of diluted RMH (7%) and 1-9% waste molasses, the highest biomass
      concentration and DHA yield reached 3.43 g/L and 8.72 mg/L, respectively. The
      algal biomass produced from RMH and molasses medium also had a high percentage of
      DHA (22-34%) in total fatty acids similar to that of commercial algal biomass.
      RMH was shown to be rich in nitrogen supply comparable to the commercial nitrogen
      feedstock like yeast extract. Using RMH as sole nitrogen source, waste molasses
      excelled other carbon sources and produced the highest concentration of biomass.
      This study suggests that DHA production of the marine dinoflagellate C. cohnii
      could be greatly improved by concomitantly using the cheap by-products rapeseed
      meal hydrolysate and molasses as alternative feedstock. 

PMID- 25942568
TI  - Electronic structure and photoelectron spectra of Bn with n = 26-29: an overview
      of structural characteristics and growth mechanism of boron clusters.
AB  - Boron clusters have been of great interest over the last few decades due to their
      unique chemical and physical properties. In the present work, we performed a
      theoretical study of geometrical and electronic structures of boron clusters Bn
      with n = 26-29 in both neutral and anionic states using DFT and MO computational
      methods. The photoelectron spectra of anionic species were simulated using TDDFT
      methods. Our results predict that in the neutral state both the B26 and B27
      clusters exhibit tubular forms, whereas the larger species B28 and B29 are quasi
      planar structures. The anionic species Bn(-) are more favourable for 2D shapes.
      More importantly, based on known geometrical characteristics, we now establish a
      general growth mechanism of boron clusters, which gives us more insight into the
      formation and existence of boron based nanomaterials. 

PMID- 25942567
TI  - A Comparison of Mental Health and Alcohol Use Between Traditional and
      Nontraditional Students.
AB  - OBJECTIVE: To describe differences in life stress, anxiety, depression, and
      alcohol use between traditional and nontraditional college students.
      PARTICIPANTS: A targeted, stratified sample of college students (N = 1,187; Mage
      = 23.96, SD = 7.30; female, 67.2%) completed study surveys in Spring 2011.
      METHODS: Participants completed demographic information, life stress (Crisis in
      Family Systems), anxiety (Beck Anxiety Inventory), depression (Center for
      Epidemiologic Studies Depression Scale), and alcohol use (Alcohol Use Disorders
      Identification Test-Consumption) surveys during regularly scheduled class times.
      RESULTS: Fifty-three percent (n = 630) of study participants were nontraditional
      students. Nontraditional students scored significantly higher than traditional
      students on life stress (t[1182] = -3.05, p < .01), anxiety (t[1175] = -2.20, p <
      .05), and depression (t[1174] = -2.22, p < .05). Nontraditional and traditional
      students did not differ on alcohol use. CONCLUSIONS: Interventions for
      nontraditional college students should address the mental health issues specific
      to this growing college subpopulation.

PMID- 25942569
TI  - Long-term effect of early-life supplementation with probiotics on preventing
      atopic dermatitis: A meta-analysis.
AB  - The prevalence of allergic diseases has increased over the past few decades.
      Atopic dermatitis (AD) is a common allergic disease, for which there is currently
      no known cure. Administration of probiotics in early life may be an effective
      method to prevent AD, but very little is known about its long-time preventive
      effect. In this research, a meta-analysis has been conducted to evaluate the long
      term effect of early-life supplementation with probiotics on preventing AD. Meta
      analysis was performed by the Review Manager version 5.2 software. Risk ratio and
      95% confidence intervals were calculated by a fixed effect model. Six trials and
      a total of 1955 patients were included in this meta-analysis. The combined risk
      ratio of the meta-analysis comparing probiotics with placebo for investigating
      the long-term preventive effect of AD was 0.86 (95% CI 0.77-0.96), which
      demonstrates that probiotics is likely to produce long-term prevention of AD. 

PMID- 25942570
TI  - Direct detection of methicillin-resistant Staphylococcus aureus in sputum
      specimens from patients with hospital-associated pneumonia using a novel
      multilocus PCR assay.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of
      hospital-associated pneumonia (HAP). The rapid identification of MRSA would be
      beneficial for early diagnosis. The study aimed to evaluate a multilocus,
      fluorescence-based PCR assay based on the detection of mecA and nuc genes for
      identification of S. aureusin lower respiratory tract (LRT) specimens.
      Sensitivity and specificity of the PCR assay were analyzed. Clinical evaluation
      for the assay was performed using LRT specimens from patients with HAP, and the
      sensitivity, specificity, positive and negative predictive values (PPV and NPV)
      were evaluated in comparison with semi-quantitative culture methods. The result
      showed the assay provided positive identification of all MRSA reference strains
      with a limit of detection for MRSA of 4 * 103 CFU/mL. Compared with semi
      quantitative culture, the sensitivity, specificity, PPV and NPV were 100%, 89.6%,
      75.0%, and 100%, respectively. A positive correlation between MRSA bacterial
      colonies and PCR copy number was found. The specificity and PPV reached 96.6% and
      89.7% respectively, if the PCR copy number reached a definite positive threshold
      of 5.96 * 105. It suggested that this novel multilocus, fluorescence-based PCR
      assay proved to be a fast, sensitive and specific tool for direct detection of
      MRSA from LRT specimens. 

PMID- 25942571
TI  - ESCRTs breach the nuclear border.
AB  - The endosomal sorting complexes required for transport (ESCRT) are best known for
      their role in sorting ubiquitylated membrane proteins into endosomes. The most
      ancient component of the ESCRT machinery is ESCRT-III, which is capable of
      oligomerizing into a helical filament that drives the invagination and scission
      of membranes aided by the AAA ATPase, Vps4, in several additional subcellular
      contexts. Our recent study broadens the work of ESCRT-III by identifying its role
      in a quality control pathway at the nuclear envelope (NE) that ensures the normal
      biogenesis of nuclear pore complexes (NPCs). Here, we will elaborate on how we
      envision this mechanism to progress and incorporate ESCRT-III into an emerging
      model of nuclear pore formation. Moreover, we speculate there are additional
      roles for the ESCRT-III machinery at the NE that broadly function to ensure its
      integrity and the maintenance of the nuclear compartment. 

PMID- 25942572
TI  - Histone deacetylases 1 and 2 regulate DNA replication and DNA repair: potential
      targets for genome stability-mechanism-based therapeutics for a subset of
      cancers.
AB  - Histone deacetylases 1 and 2 (HDAC1,2) belong to the class I HDAC family, which
      are targeted by the FDA-approved small molecule HDAC inhibitors currently used in
      cancer therapy. HDAC1,2 are recruited to DNA break sites during DNA repair and to
      chromatin around forks during DNA replication. Cancer cells use DNA repair and
      DNA replication as survival mechanisms and to evade chemotherapy-induced
      cytotoxicity. Hence, it is vital to understand how HDAC1,2 function during the
      genome maintenance processes (DNA replication and DNA repair) in order to gain
      insights into the mode-of-action of HDAC inhibitors in cancer therapeutics. The
      first-in-class HDAC1,2-selective inhibitors and Hdac1,2 conditional knockout
      systems greatly facilitated dissecting the precise mechanisms by which HDAC1,2
      control genome stability in normal and cancer cells. In this perspective, I
      summarize the findings on the mechanistic functions of class I HDACs,
      specifically, HDAC1,2 in genome maintenance, unanswered questions for future
      investigations and views on how this knowledge could be harnessed for better
      targeted cancer therapeutics for a subset of cancers. 

PMID- 25942573
TI  - Development of a screening fluorescence polarization immunoassay for the
      simultaneous detection of fumonisins B1 and B2 in maize.
AB  - This paper reports the development of a screening fluorescence polarization
      immunoassay (FPIA) for the simultaneous detection of fumonisins B1 (FB1) and B2
      (FB2) in maize. Three FB1 tracers including FB1-fluorescein isothiocyanate isomer
      I (FB1-FITC), FB1-5-([4,6-dichlorotriazine-2-yl]amino)-fluorescein (FB1-5-DTAF),
      and FB1-Texas Red-X succinimidyl ester (FB1-TRX) were synthesized and studied to
      select appropriate tracer-antibody pairs using seven previously produced
      monoclonal antibodies (mAbs). An FPIA employing the pair of FB1-FITC and mAb 4B9
      showing 98.9% cross-reactivity (CR) toward FB2 was used to simultaneously detect
      FB1 and FB2. Maize flour samples were extracted with methanol/water (2:3, v/v).
      After optimization, the FPIA revealed a limit of detection (LOD) of 157.4 MUg/kg
      for FB1 and an LOD of 290.6 MUg/kg for FB2, respectively. Recoveries were
      measured for spiked samples of FB1 or FB2 separately, ranging from 84.7 to 93.6%,
      with a coefficient of variation (CV) of <9.9%. Total time needed for FPIA
      including sample pretreatment was <30 min. The FPIA was used to screen naturally
      contaminated maize samples. Results detected by FPIA showed good agreement with
      that of HPLC-MS/MS with a fit of R(2) = 0.99 for the simultaneous detection of
      FB1 and FB2. The established method offered a rapid, simple, sensitive, and high
      throughput screening tool for the detection of fumonisins in maize. 

PMID- 25942574
TI  - Crossreactivity to vinculin and microbes provides a molecular basis for HLA-based
      protection against rheumatoid arthritis.
AB  - The HLA locus is the strongest risk factor for anti-citrullinated protein
      antibody (ACPA)(+) rheumatoid arthritis (RA). Despite considerable efforts in the
      last 35 years, this association is poorly understood. Here we identify
      (citrullinated) vinculin, present in the joints of ACPA(+) RA patients, as an
      autoantigen targeted by ACPA and CD4(+) T cells. These T cells recognize an
      epitope with the core sequence DERAA, which is also found in many microbes and in
      protective HLA-DRB1*13 molecules, presented by predisposing HLA-DQ molecules.
      Moreover, these T cells crossreact with vinculin-derived and microbial-derived
      DERAA epitopes. Intriguingly, DERAA-directed T cells are not detected in HLA
      DRB1*13(+) donors, indicating that the DERAA epitope from HLA-DRB1*13 mediates
      (thymic) tolerance in these donors and explaining the protective effects
      associated with HLA-DRB1*13. Together our data indicate the involvement of
      pathogen-induced DERAA-directed T cells in the HLA-RA association and provide a
      molecular basis for the contribution of protective/predisposing HLA alleles. 

PMID- 25942575
TI  - Bright white light therapy in depression: A critical review of the evidence.
AB  - BACKGROUND: Light therapy is an accepted treatment option, at least for seasonal
      affective disorder (SAD). Our aim was to critically evaluate treatment effects of
      bright white light (BWL) on the depressive symptoms in both SAD and non-seasonal
      depression. METHODS: The systematic review was performed according to the PRISMA
      guidelines. PubMed, Embase, and PsycINFO were searched (December 1974 through
      June 2014) for randomized controlled trials published in peer-reviewed journals.
      Study quality was assessed with a checklist developed by the Swedish Council on
      Technology Assessment in Health Care. Only studies with high or medium quality
      were used in the meta-analyses. RESULTS: Eight studies of SAD and two studies of
      non-seasonal depression met inclusion and quality criteria. Effects on SAD were
      estimated in two meta-analyses. In the first, week by week, BWL reached
      statistical significance only at two and three weeks of treatment (Standardized
      Mean Difference, SMD: -0.50 (-CI 0.94, -0.05); -0.31 (-0.59, -0.03)
      respectively). The second meta-analysis, of endpoint data only, showed a SMD of 
      0.54 (CI: -0.95, -0.13), which indicates an advantage for BWL. No meta-analysis
      was performed for non-seasonal depression due to heterogeneity between studies.
      LIMITATIONS: This analysis is restricted to short-term effects of BWL measured as
      mean changes in scores derived from SIGH-SAD, SIGH-SAD self-report, or HDRS
      rating scales. CONCLUSIONS: Most studies of BWL have considerable methodological
      problems, and the results of published meta-analyses are highly dependent on the
      study selection. Even though quality criteria are introduced in the selection
      procedures of studies, when the results are carefully scrutinized, the evidence
      is not unequivocal.

PMID- 25942576
TI  - Altered effective connectivity model in the default mode network between bipolar
      and unipolar depression based on resting-state fMRI.
AB  - BACKGROUND: Bipolar depression (BD) is characterized by alternating episodes of
      depression and mania. Patients who spend the majority of their time in episodes
      of depression rather than mania are often misdiagnosed with unipolar depression
      (UD) that only exhibits depressive episodes. It would be important to explore the
      construction of more objective biomarkers which can be used to more accurately
      differentiate BD and UD. METHODS: The effective connectivity model of BD and UD
      in the default mode network (DMN) was constructed based on resting-state fMRI
      data of 17 BD (32.12+/-8.57 years old) and 17 UD (32.59+/-9.77 years old)
      patients using a linear non-Gaussian acyclic model (LiNGAM). The effective
      connectivity differences were obtained by conducting a permutation test. RESULTS:
      The following connections were stronger in the BD group than in the UD group:
      medial prefrontal cortex (MPFC) ->posterior cingulate cortex (PCC), right
      inferior parietal cortex (rIPC)->left hippocampus (lHC) and rIPC->right insula
      (rInsula). In contrast, the following connections were weak or unapparent in the
      BD group: MPFC->lHC, rHC->MPFC, rHC->rInsula and rInsula->lHC. LIMITATIONS:
      First, the medication effect is a confounding factor. Second, as with most fMRI
      studies, the subjects' thoughts during imaging are difficult to control.
      CONCLUSIONS: The brain regions in these altered connections, such as the HC,
      insula, MPFC and IPC, all play important roles in emotional processing,
      suggesting that these altered connections may be conducive to better distinguish
      between BD and UD.

PMID- 25942577
TI  - Genomic heritability: what is it?
AB  - Whole-genome regression methods are being increasingly used for the analysis and
      prediction of complex traits and diseases. In human genetics, these methods are
      commonly used for inferences about genetic parameters, such as the amount of
      genetic variance among individuals or the proportion of phenotypic variance that
      can be explained by regression on molecular markers. This is so even though some
      of the assumptions commonly adopted for data analysis are at odds with important
      quantitative genetic concepts. In this article we develop theory that leads to a
      precise definition of parameters arising in high dimensional genomic regressions;
      we focus on the so-called genomic heritability: the proportion of variance of a
      trait that can be explained (in the population) by a linear regression on a set
      of markers. We propose a definition of this parameter that is framed within the
      classical quantitative genetics theory and show that the genomic heritability and
      the trait heritability parameters are equal only when all causal variants are
      typed. Further, we discuss how the genomic variance and genomic heritability,
      defined as quantitative genetic parameters, relate to parameters of statistical
      models commonly used for inferences, and indicate potential inferential problems
      that are assessed further using simulations. When a large proportion of the
      markers used in the analysis are in LE with QTL the likelihood function can be
      misspecified. This can induce a sizable finite-sample bias and, possibly, lack of
      consistency of likelihood (or Bayesian) estimates. This situation can be
      encountered if the individuals in the sample are distantly related and linkage
      disequilibrium spans over short regions. This bias does not negate the use of
      whole-genome regression models as predictive machines; however, our results
      indicate that caution is needed when using marker-based regressions for
      inferences about population parameters such as the genomic heritability. 

PMID- 25942578
TI  - Agreement of central site measurements and land use regression modeled oxidative
      potential of PM2.5 with personal exposure.
AB  - Oxidative potential (OP) of ambient particulate matter (PM) has been suggested as
      a health-relevant exposure metric. In order to use OP for exposure assessment,
      information is needed about how well central site OP measurements and modeled
      average OP at the home address reflect temporal and spatial variation of personal
      OP. We collected 96-hour personal, home outdoor and indoor PM2.5 samples from 15
      volunteers living either at traffic, urban or regional background locations in
      Utrecht, the Netherlands. OP was also measured at one central reference site to
      account for temporal variations. OP was assessed using electron spin resonance
      (OP(ESR)) and dithiothreitol (OP(DTT)). Spatial variation of average OP at the
      home address was modeled using land use regression (LUR) models. For both OP(ESR)
      and OP(DTT), temporal correlations of central site measurements with home outdoor
      measurements were high (R>0.75), and moderate to high (R=0.49-0.70) with personal
      measurements. The LUR model predictions for OP correlated significantly with the
      home outdoor concentrations for OP(DTT) and OP(ESR) (R=0.65 and 0.62,
      respectively). LUR model predictions were moderately correlated with personal
      OP(DTT) measurements (R=0.50). Adjustment for indoor sources, such as vacuum
      cleaning and absence of fume-hood, improved the temporal and spatial agreement
      with measured personal exposure for OP(ESR). OP(DTT) was not associated with any
      indoor sources. Our study results support the use of central site OP for exposure
      assessment of epidemiological studies focusing on short-term health effects. 

PMID- 25942579
TI  - Healthcare Professionals' Perceptions of the Benefits and Challenges of a
      Teleconsultation Service in the Amansie-West District of Ghana.
AB  - OBJECTIVES: A teleconsultation service was introduced in the Amansie-West
      District, Ghana, in 2010 linking health center-based community health nurses
      (CHNs) with a teleconsultation center (TCC) at the district hospital. This study
      aimed to assess healthcare professionals' perceptions of the benefits and
      challenges of this service and to identify possible areas for improvement.
      MATERIALS AND METHODS: Qualitative semistructured interviews were conducted with
      eight CHNs and three TCC healthcare professionals to find their views on the
      benefits, challenges, and recommendations for improving the service. The data
      were analyzed using qualitative content analysis. RESULTS: Interviewees were
      generally positive when describing the use of the teleconsultation service. They
      were of the opinion that the service had improved the quality of care at health
      centers, thus reducing the need to refer patients to the district hospital.
      Practical problems, such as inadequate information provided over the phone,
      delays in responding to calls, and the additional workload for teleconsultation
      staff, were viewed as important challenges to the success of the project.
      Interviewees identified several possible options for improving the service
      through extension to other levels of the healthcare system or by adding
      additional functionalities to their phones. CONCLUSIONS: Teleconsultation
      services have the potential to improve quality of care in rural communities.
      However, practical problems in the operation of the service have to be taken
      seriously as they threaten sustainability of the intervention. Adequate training
      in phone-based clinical reporting appears to be essential. Teleconsultation staff
      should be compensated for additional workload through a reduction of other work
      related tasks.

PMID- 25942582
TI  - Water in N-heterocyclic carbene-assisted catalysis.

PMID- 25942580
TI  - Anti-IL-12/23p40 antibodies for induction of remission in Crohn's disease.
AB  - BACKGROUND: Ustekinumab (CNTO 1275) and briakinumab (ABT-874) are monoclonal
      antibodies that target the standard p40 subunit of the cytokines interleukin-12
      and interleukin-23 (IL-12/23p40), which are involved in the pathogenesis of
      Crohn's disease. OBJECTIVES: The objectives of this review were to assess the
      efficacy and safety of anti-IL-12/23p40 antibodies for induction of remission in
      Crohn's disease. SEARCH METHODS: The following databases were searched from
      inception to September 16, 2014: PubMed, MEDLINE, EMBASE, and the Cochrane
      Library (CENTRAL). References and conference abstracts were searched to identify
      additional studies. SELECTION CRITERIA: Randomized controlled trials (RCTs)
      trials in which monoclonal antibodies against IL-12/23p40 were compared to
      placebo or another active comparator in patients with active Crohn's disease were
      included.  DATA COLLECTION AND ANALYSIS: Two authors independently screened 
      studies for inclusion and extracted data. Methodological quality was assessed
      using the Cochrane risk of bias tool. The primary outcome was failure to induce
      clinical remission, defined as a Crohn's disease activity index (CDAI) of < 150
      points. Secondary outcomes included failure to induce clinical improvement,
      serious adverse events, and withdrawals due to adverse events. Clinical
      improvement was defined as decreases of > 70 or > 100 points in the CDAI from
      baseline. We calculated the risk ratio (RR) and 95% confidence intervals (95% CI)
      for each outcome. A fixed-effect model was used to pool data. Data were analyzed
      on an intention-to-treat basis. The overall quality of the evidence supporting
      the outcomes was evaluated using the GRADE criteria. MAIN RESULTS: Four
      randomized controlled trials (n = 955 patients) met the inclusion criteria. A low
      risk of bias was assigned to all studies. The two briakinumab trials were not
      pooled due to differences in doses and time points for analysis. In both studies
      there was no statistically significant difference in remission rates. One study
      (n = 79) compared doses of 1 mg/kg and 3 mg/kg to placebo. In the briakinumab
      group 70% (44/63) of patients failed to enter clinical remission at 6 or 9 weeks
      compared to 81% (13/16) of placebo patients (RR 0.86, 95% CI 0.65 to 1.14).
      Subgroup analysis revealed no significant differences by dose. The other
      briakinumab study (n = 230) compared intravenous doses of 200 mg, 400 mg and 700
      mg with placebo. Eighty-four per cent (154/184) of briakinumab patients failed to
      enter clinical remission at six weeks compared to 91% (42/46) of placebo patients
      (RR 0.92, 95% CI 0.83 to 1.03). Subgroup analysis revealed no significant
      differences by dose. GRADE analyses of the briakinumab studies rated the overall
      quality of the evidence for the outcome clinical remission as low due. Based on
      the results of these two studies the manufacturers of briakinumab stopped
      production of this medication. The two ustekinumab studies (630 patients) were
      pooled despite differences in intravenous doses (i.e. 1mg/kg, 3 mg/kg, 4.5 mg/kg,
      and 6 mg/kg), however the subcutaneous dose group was not included in the
      analysis, as it was unclear if subcutaneous was equivalent to intravenous dosing.
      There was no statistically significant difference in remission rates. At week
      six, 85% (356/420) of ustekinumab patients failed to enter remission compared to
      89% (142/159) of placebo patients (RR 0.94, 95% CI 0.88 to 1.01). Subgroup
      analysis showed no statistically significant difference by dose. There were
      statistically significant differences in clinical improvement between ustekinumab
      and placebo-treated patients. In the ustekinumab group, 55% (230/420) of patients
      failed to improve clinically (i.e. 70-point decline in CDAI score), compared to
      72% (115/159) of placebo patients (RR 0.75, 95% CI 0.66 to 0.86). Subgroup
      analysis revealed significant differences compared to placebo for the 1 mg/kg,
      4.5 mg/kg and 6 mg/kg dosage subgroups. Similarly for a 100-point decline in
      CDAI, 62% (262/420) of patients in the ustekinumab group failed to improve
      clinically compared to 78% (124/159) of placebo patients (RR 0.79, 95% CI 0.71 to
      0.89). Subgroup analysis showed a significant difference compared to placebo for
      the 4.5 mg/kg dose group. GRADE analyses of the ustekinumab studies rated the
      overall quality of the evidence for the outcomes clinical remission and clinical
      response as moderate. There were no statistically significant differences in the
      incidence of adverse events, serious adverse events or withdrawal due to adverse
      events. Sixty-seven per cent (316/473) of ustekinumab patients developed at least
      one adverse event compared to 73% (135/184) of placebo patients (RR 0.92, 95% CI
      0.83 to 1.03). A GRADE analysis indicated that the overall quality of the
      evidence for this outcome was high. Six per cent (29/473) of ustekinumab patients
      had a serious adverse event compared to 8% (14/184) of placebo patients (RR 0.81,
      95% CI 0.44 to 1.49). A GRADE analysis indicated that the overall quality of the
      evidence for this outcome was low. The most common adverse events in briakinumab
      patients were injection site reactions and infections. Infections were the most
      common adverse event in ustekinumab patients. Worsening of Crohn's disease and
      serious infections were the most common serious adverse events. AUTHORS'
      CONCLUSIONS: Although we are uncertain about the efficacy of ustekinumab for
      induction of remission, moderate quality evidence suggests that ustekinumab may
      be effective for induction of clinical improvement in patients with moderate to
      severe CD. Due to small numbers of patients in dose subgroups the optimal dosage
      of ustekinumab is unclear. Briakinumab and ustekinumab appear to be safe. Due to
      sparse data we were unable to determine the risk of serious adverse events.
      Further studies are required to determine the efficacy and safety of ustekinumab
      in patients with moderate to severe CD. The results of three phase III trials
      that are currently underway will provide important new information.

PMID- 25942583
TI  - Human umbilical cord matrix mesenchymal stem cells suppress the growth of breast
      cancer by expression of tumor suppressor genes.
AB  - Human and rat umbilical cord matrix mesenchymal stem cells (UCMSC) possess the
      ability to control the growth of breast carcinoma cells. Comparative analyses of
      two types of UCMSC suggest that rat UCMSC-dependent growth regulation is
      significantly stronger than that of human UCMSC. Their different tumoricidal
      abilities were clarified by analyzing gene expression profiles in the two types
      of UCMSC. Microarray analysis revealed differential gene expression between
      untreated naive UCMSC and those co-cultured with species-matched breast carcinoma
      cells. The analyses screened 17 differentially expressed genes that are commonly
      detected in both human and rat UCMSC. The comparison between the two sets of gene
      expression profiles identified two tumor suppressor genes, adipose
      differentiation related protein (ADRP) and follistatin (FST), that were
      specifically up-regulated in rat UCMSC, but down-regulated in human UCMSC when
      they were co-cultured with the corresponding species' breast carcinoma cells.
      Over-expression of FST, but not ADRP, in human UCMSC enhanced their ability to
      suppress the growth of MDA-231 cells. The growth of MDA-231 cells was also
      significantly lower when they were cultured in medium conditioned with FST, but
      not ADRP over-expressing human UCMSC. In the breast carcinoma lung metastasis
      model generated with MDA-231 cells, systemic treatment with FST-over-expressing
      human UCMSC significantly attenuated the tumor burden. These results suggest that
      FST may play an important role in exhibiting stronger tumoricidal ability in rat
      UCMSC than human UCMSC and also implies that human UCMSC can be transformed into
      stronger tumoricidal cells by enhancing tumor suppressor gene expression. 

PMID- 25942585
TI  - Syntheses of Dihydroconduramines (+/-)-B-1, (+/-)-E-1, and (+/-)-F-1 via
      Diastereoselective Epoxidation of N-Protected 4-Aminocyclohex-2-en-1-ols.
AB  - Diastereoselective syntheses of dihydroconduramines (+/-)-B-1, (+/-)-E-1, and (+/
      )-F-1 have been achieved from N-protected 4-aminocyclohex-2-en-1-ols via two
      complementary procedures for epoxidation as the key step. Treatment of either
      trans- or cis-4-N-benzylaminocyclohex-2-en-1-ol with Cl3CCO2H and then m
      chloroperoxybenzoic acid (m-CPBA) resulted in initial formation of the
      corresponding ammonium species, followed by epoxidation on the face syn to the
      ammonium moiety exclusively; chemoselective N-benzylation then provided either
      (1RS,2SR,3RS,4RS)- or (1RS,2RS,3SR,4SR)-2,3-epoxy-4-N,N-dibenzylaminocyclohexan-1
      ol, respectively. Treatment of either trans- or cis-4-N,N-dibenzylaminocyclohex-2
      en-1-ol with m-CPBA resulted in initial formation of the corresponding N-oxide,
      followed by epoxidation on the face syn to the hydroxyl group exclusively;
      reduction then provided either (1RS,2RS,3SR,4RS)- or an alternative route to
      (1RS,2RS,3SR,4SR)-2,3-epoxy-4-N,N-dibenzylaminocyclohexan-1-ol, respectively. In
      all cases, S(N)2-type ring opening of these epoxides upon treatment with aqueous
      H2SO4 proceeded by nucleophilic attack with inversion at C(2) preferentially,
      distal to the in situ formed ammonium moiety. Hydrogenolytic N-deprotection then
      gave the corresponding dihydroconduramines (+/-)-B-1, (+/-)-E-1, and (+/-)-F-1.

PMID- 25942584
TI  - Body mass index, mortality, and gender difference in advanced chronic kidney
      disease.
AB  - BACKGROUND AND AIM: A higher body mass index (BMI) appears to be reversely
      associated with mortality in dialysis patients. Moreover, although women have
      better survival in chronic kidney disease (CKD), this survival advantage is
      cancelled in dialysis. The association between BMI and mortality and the gender
      difference remain controversial in advanced CKD. METHODS: This study enrolled
      3,320 patients (1,938 men and 1,382 women) from southern Taiwan who had CKD
      stages 3-5 with a BMI of 15.0-35.0 kg/m2. RESULTS: During a median 2.9-year
      follow-up, there were 328 (16.9%) all-cause mortality and 319 (16.5%)
      cardiovascular (CV) events and death in male patients, 213 (15.4%) all-cause
      mortality and 224 (16.2%) CV events and death in female patients. Compared with
      the reference BMI of 27.6-30.0 kg/m2 in an adjusted Cox model, lower-BMI groups
      in men, BMI 15.0-20.0 kg/m2 and 20.1-22.5 kg/m2, were associated with higher
      risks of all-cause mortality: hazard ratios (HRs) 3.19 (95% confidence interval
      [CI], 1.97-5.18) and 2.01 (95% CI, 1.29-3.14), respectively. Higher-BMI group in
      men, BMI 30.1-35.0 kg/m2, was associated with a higher risk of all-cause
      mortality: HR 1.72 (95% CI, 1.02-2.96). Likewise, lower- and higher-BMI groups in
      men were associated with a higher risk of CV events and death. In women, these
      associations between BMI and poor outcomes were not observed. CONCLUSIONS: In
      advanced CKD, there was a reverse J-shaped association between BMI and all-cause
      mortality, and a U-shaped association between BMI and CV outcomes in men. Neutral
      associations between BMI and poor outcomes were detected in women. Gender could
      modify the effect of BMI on mortality in patients with CKD.

PMID- 25942586
TI  - A hydrodynamic instability is used to create aesthetically appealing patterns in
      painting.
AB  - Painters often acquire a deep empirical knowledge of the way in which paints and
      inks behave. Through experimentation and practice, they can control the way in
      which fluids move and deform to create textures and images. David Alfaro
      Siqueiros, a recognized Mexican muralist, invented an accidental painting
      technique to create new and unexpected textures. By pouring layers of paint of
      different colors on a horizontal surface, the paints infiltrate into each other
      creating patterns of aesthetic value. In this investigation, we reproduce the
      technique in a controlled manner. We found that for the correct color
      combination, the dual viscous layer becomes Rayleigh-Taylor unstable: the density
      mismatch of the two color paints drives the formation of a spotted pattern.
      Experiments and a linear instability analysis were conducted to understand the
      properties of the process. We also argue that this flow configuration can be used
      to study the linear properties of this instability. 

PMID- 25942587
TI  - Topical application of Scutellaria baicalensis suppresses 2,4
      dinitrochlorobenzene-induced contact dermatitis.
AB  - Allergic contact dermatitis (ACD) is a prototypic T-cell-mediated cutaneous
      inflammatory response. In the present study we describe the anti-allergic effect
      of topically applied Scutellaria bacalensis aqueous extract (WSBE) in suppressing
      2,4-dinitrochlorobenzene (DNCB)-induced ACD in BALB/c mice. Topically applied
      WSBE attenuated the epidermal thickness and mast cell infiltration into the skin
      in DNCB-induced contact dermatitis. Furthermore, WSBE suppressed DNCB-induced
      production of serum IgE as well as IL-4, IFN-gamma, and TNF-alpha in the skin.
      Topical application of WSBE also ameliorated the significant decrease in dermal
      glutathione and superoxide dismutase levels. Moreover, present results
      demonstrated that the baicalin, bioactive compound of WSBE, was able to penetrate
      into the skin following topical application, which was confirmed by the HPLC
      analysis using rat model. Taken together, topical application of WSBE exerts
      beneficial effects in contact dermatitis model, suggesting that WSBE might be a
      candidate for the treatment of contact dermatitis. 

PMID- 25942589
TI  - Environmental Distributions of Benzo[a]pyrene in China: Current and Future
      Emission Reduction Scenarios Explored Using a Spatially Explicit Multimedia Fate
      Model.
AB  - SESAMe v3.0, a spatially explicit multimedia fate model with 50 * 50 km(2)
      resolution, has been developed for China to predict environmental concentrations
      of benzo[a]pyrene (BaP) using an atmospheric emission inventory for 2007. Model
      predictions are compared with environmental monitoring data obtained from an
      extensive review of the literature. The model performs well in predicting
      multimedia concentrations and distributions. Predicted concentrations are
      compared with guideline values; highest values with some exceedances occur mainly
      in the North China Plain, Mid Inner Mongolia, and parts of three northeast
      provinces, Xi'an, Shanghai, and south of Jiangsu province, East Sichuan Basin,
      middle of Guizhou and Guangzhou. Two potential future scenarios have been
      assessed using SESAMe v3.0 for 2030 as BaP emission is reduced by (1)
      technological improvement for coal consumption in energy production and industry
      sectors in Scenario 1 (Sc1) and (2) technological improvement and control of
      indoor biomass burning for cooking and indoor space heating and prohibition of
      open burning of biomass in 2030 in Scenario 2 (Sc2). Sc2 is more efficient in
      reducing the areas with exceedance of guideline values. Use of SESAMe v3.0
      provides insights on future research needs and can inform decision making on
      options for source reduction. 

PMID- 25942590
TI  - Challenges of modelling real nanoparticles: Ni@Pt electrocatalysts for the oxygen
      reduction reaction.
AB  - Theoretical/computational methods have been extensively applied to screen
      possible nano-structures attempting to maximize catalytic and stability
      properties for applications in electrochemical devices. This work shows that the
      method used to model core@shell structures is of fundamental importance in order
      to truly represent the physicochemical changes arising from the formation of a
      core-shell structure. We demonstrate that using a slab approach for modelling
      nanoparticles the oxygen adsorption energies are qualitatively well represented.
      Although this is a good descriptor for the catalytic activity, huge differences
      are found for the calculated surface stability between the results of a nano
      cluster and those of a slab approach. Moreover, for the slab method depending on
      the geometric properties of the core and their similarity to the elements of the
      core or shell, contradictory effects are obtained. In order to determine the
      changes occurring as the number of layers and nano particle size are increased,
      clusters of Ni@Pt from 13 to 260 atoms were constructed and analyzed in terms of
      geometric parameters, oxygen adsorption, and dissolution potential shift. It is
      shown that the results of modelling the Ni@Pt nanoparticles with a cluster
      approach are in good agreement with experimental geometrical parameters,
      catalytic activity, and stability of a carefully prepared series of Ni@Pt
      nanostructures where the shell thickness is systematically changed. The maximum
      catalytic activity and stability are found for a monolayer of Pt whereas adding a
      second and third layer the behavior is almost the same than that in pure Pt
      nanoparticles. 

PMID- 25942588
TI  - Pathways of Leymus chinensis Individual Aboveground Biomass Decline in Natural
      Semiarid Grassland Induced by Overgrazing: A Study at the Plant Functional Trait
      Scale.
AB  - Natural grassland productivity, which is based on an individual plant's
      aboveground biomass (AB) and its interaction with herbivores, can obviously
      affect terrestrial ecosystem services and the grassland's agricultural
      production. As plant traits have been linked to both AB and ecosystem success,
      they may provide a useful approach to understand the changes in individual plants
      and grassland productivity in response to grazing on a generic level.
      Unfortunately, the current lack of studies on how plant traits affect AB affected
      by herbivores leaves a major gap in our understanding of the mechanism of
      grassland productivity decline. This study, therefore, aims to analyze the paths
      of overgrazing-induced decline in the individual AB of Leymus chinensis (the
      dominant species of meadow-steppe grassland in northern China) on a plant
      functional trait scale. Using a paired-sampling approach, we compared the
      differences in the functional traits of L. chinensis in long-term grazing
      excluded and experimental grazing grassland plots over a continuous period of
      approximately 20 years (located in meadow steppe lands in Hailar, Inner Mongolia,
      China). We found a highly significant decline in the individual height and
      biomass (leaf, stem, and the whole plant) of L. chinensis as a result of
      overgrazing. Biomass allocation and leaf mass per unit area were significantly
      affected by the variation in individual size. Grazing clearly enhanced the
      sensitivity of the leaf-to-stem biomass ratio in response to variation in
      individual size. Moreover, using a method of standardized major axis estimation,
      we found that the biomass in the leaves, stems, and the plant as a whole had
      highly significant allometric scaling with various functional traits. Also, the
      slopes of the allometric equations of these relationships were significantly
      altered by grazing. Therefore, a clear implication of this is that grazing
      promotes an asymmetrical response of different plant functional traits to
      variation in individual plant size, which influences biomass indirectly.
      Furthermore, we detected paths of individual AB decline in L. chinensis induced
      by grazing by fitting to a structural equation model. These results indicate that
      grazing causes AB decline primarily through a 'bottom-up' effect on plant height
      and stem traits. However, leaf traits, via the process of allometric scaling,
      affect plant AB indirectly. 

PMID- 25942591
TI  - : wound healing outcomes: the impact of site of care and patient stratification.
AB  - As healthcare providers prepare for pay for performance (P4P) and outcomes
      based reimbursement strategies, it is increasingly important to document clinical
      results. Historically, healing rates have been reported from hospital-based,
      outpatient wound clinics. Time-to-healing curves from one site of care may not
      accurately reflect the entire healing "episode of care." Few outpatients from a
      wound clinic require hospitalization and even fewer are admitted to sub-acute
      care. Care setting and population risk strata must be clearly identified before
      comparing wound outcomes data. AIM: Primary objectives were to determine
      comparability of complete healing and 50% wound volume reduction of current and
      prior sub-acute care programs. Predictive value of Minimum Data Set (MDS 2.0)
      items on admission was also explored in discriminating healing versus nonhealing
      patients. METHODS: Wound outcomes were analyzed for all patients (N = 101)
      treated at a dedicated sub-acute wound unit from January 2006 through April 2007
      in a prospective, longitudinal, intent-to-treat, cohort study. Results were
      compared to prior sub-acute care wound outcomes reported by a similarly composed
      team using similar protocols. RESULTS: Of 101 evaluable patients with 209 wounds,
      41.6% healed in a median of 7.9 weeks while 31.6% achieved > 50% volume
      reduction. Outcomes were similar to prior sub-acute results, but less than the
      72%-74% healing rate reported by a similar team in hospital outpatient clinic
      programs. Minimum Data Set comorbidities analyzed did not significantly predict
      nonhealing. CONCLUSION: To allow risk-adjusted P4P and reimbursement metrics,
      wound outcome reports should include clinical team involved, protocol
      utilization, care setting, and case mix severity to control for variables
      associated with different settings.

PMID- 25942592
TI  -  Measuring wound outcomes.
AB  - Chronic cutaneous wounds include leg ulcers, pressure ulcers, and diabetic foot
      ulcers. Each of these conditions is difficult to heal within an acceptably short
      time, and to maintain as healed. Patients suffer tremendous discomfort and pain,
      and are often socially deprived as a result. The financial consequences of this
      medical problem are enormous. Chronic or nonhealing ulcers are characterized by
      defective remodeling of the extracellular matrix, a failure to reepithelialize,
      and prolonged inflammation. In order to obtain biochemical and physical
      information about the wound bed and the surrounding skin, different options of
      noninvasive and invasive measurements have been developed and tested. Monitoring
      of acute and chronic wounds can be performed by measuring in an objective,
      precise, and reproducible way and by simply adapting existing validated
      technologies. When speaking of cutaneous wounds, one refers to defects in the
      skin surface. It is generally believed that a full and correct characterization
      of the level of tissue damage must be carried out by analyzing 2 distinct groups
      of parameters: dimensional parameters and chromatic parameters. Recently, the
      concept of wound bed preparation has been introduced and classified according to
      the clinical parameters of chronic wounds. In order to monitor the different
      aspects of wound bed preparation, various instrumental techniques are now under
      investigation, allowing improved, more objective characterization of the tissue
      repair process. The advantage of this new scientific discipline is the ability to
      study living skin in real time. The main physical wound parameters that have
      received the most attention over the past few years in terms of outcome in wound
      measurement are: area and volume, color, surface pH, temperature, wound fluid
      analysis, odor, pain, and tissue perfusion. 

PMID- 25942593
TI  - Closing the Gap Between Evidence and Action: How Outcome Measurement Informs the
      Implementation of Evidence-based Wound Care Practice in Home Care.
AB  - Measured outcomes can help assure successful implementation of evidence-based
      wound care programs by informing patients, professionals, and payors that a
      health care system is both efficient and effective. OBJECTIVE: Illustrate how
      clinical and economic outcome measurement was important to ensure sustainability
      of standardized evidence-based wound care programs implemented in Canadian
      community care. METHODS: Client assessments, dressing change frequency, wound
      healing, and economic outcomes were measured on 16,079 Canadian home care
      clients, including 8089 with a total of 11,160 chronic or acute wounds during
      standardized evidence-based protocol implementation that involved education,
      knowledge transfer, strategic planning, management accountability/receptivity,
      communication, and either prospective client assessment-based data or
      retrospective chart audit data to measure outcomes. RESULTS: Results from 3
      regions illustrate how evidence-based protocol use decreased length of service,
      dressing change frequency, wound care costs, and wound closure time. Client and
      staff empowerment and management involvement were among key factors for success.
      CONCLUSION: Objectively measuring and reporting outcomes provided a concrete
      context for increasing organizational efforts to improve wound care practices and
      provided a solid foundation for sustained evidence-based protocol usage as it
      allowed agencies to track improvement in health and economic outcomes.

PMID- 25942594
TI  - Incidence and Clinical Symptoms of Hourglass and Sandwich-shaped Tissue Necrosis
      in Stage IV Pressure Ulcer.
AB  - Measuring pressure ulcer outcomes for deep tissue injury (DTI) in pressure
      ulcers has improved the authors' understanding of DTI. The authors'
      multidisciplinary team has also identified previously unexplored patterns of
      tissue necrosis. OBJECTIVE: Illustrate these new patterns of tissue necrosis and
      report their incidence in a hospital setting. METHODS: Progressive tissue
      deterioration was explored using CT scans and ultrasonography of 326 Stage IV
      pressure ulcers with deep tissue injuries (DTI) managed by a multidisciplinary
      wound care team using standardized protocols of care in a Japanese hospital from
      June 2002 to June 2006. RESULTS: Two new patterns of pressure ulcer necrosis were
      found and are illustrated. All patients were checked consecutively and treated by
      the multidisciplinary team every 2 weeks. Among the consecutive sample of 326
      patients, 194 (60%) were common DTI with column-shaped necrosis, including 7 with
      relatively healthy tissue sandwiched between shallow and deep necrosis. The
      remaining 132 (40%) had hourglass-shaped area of necrosis, including 20 with
      sandwiched-shaped necrosis. Hourglass shaped necrosis was associated with a
      combination of shear forces and pressure over a bony prominence. Sandwich-shaped
      hourglass necrosis often appeared to heal the superficial tissue but was reopened
      with deep necrosis that liquified and sloughed. CONCLUSION: Understanding the
      morphology and course of deterioration and healing of these different types of
      necrosis has helped the team recognize and manage previously unpredictable DTI,
      improving staff, patient, and family expectations, and reducing misunderstandings
      about pressure ulcer development.

PMID- 25942595
TI  - Preventing infections to improve wound care outcomes: an epidemiological
      approach.
AB  - Measuring and tracking wound complications and associated risk factors are
      powerful tools in managing wound outcomes. The authors review fundamental
      epidemiological approaches to clinical investigation, beginning with some basic
      study designs, and their relative strengths and weaknesses, with respect to the
      usefulness of the findings. Examples of methods to calculate rates and
      proportions and ways to measure significant change over time are presented. A
      conceptual model that is universally used by infection prevention professionals
      in the development and implementation of prevention strategies is also described.
      Risk stratification systems that have been derived through the analysis of
      thousands of patients are presented. These systems help predict those patients
      who are at risk for developing adverse outcomes (eg, infections or pressure
      ulcers), and therefore, should help caregivers address those risks by applying
      scientifically derived prevention strategies. Finally, various prevention
      strategies and how they relate to the conceptual model of infection prevention
      are discussed. 

PMID- 25942596
TI  - The characteristic changes in hepatitis B virus x region for hepatocellular
      carcinoma: a comprehensive analysis based on global data.
AB  - OBJECTIVES: Mutations in hepatitis B virus (HBV) X region (HBx) play important
      roles in hepatocarcinogenesis while the results remain controversial. We sought
      to clarify potential hepatocellular carcinoma (HCC)-characteristic mutations in
      HBx from HBV genotype C-infected patients and the distribution of those mutations
      in different disease phases and genotypes. METHODS: HBx sequences downloaded from
      an online global HBV database were screened and then classified into Non-HCC or
      HCC group by diagnosis information. Patients' data of patient age, gender,
      country or area, and viral genotype were also extracted. Logistic regression was
      performed to evaluate the effects of mutations on HCC risk. RESULTS: 1) Full
      length HBx sequences (HCC: 161; Non-HCC: 954) originated from 1115 human sera
      across 29 countries/areas were extracted from the downloaded 5956 HBx sequences.
      Genotype C occupied 40.6% of Non-HCC (387/954) and 89.4% of HCC (144/161). 2)
      Sixteen nucleotide positions showed significantly different distributions between
      genotype C HCC and Non-HCC groups. 3) Logistic regression showed that mutations
      A1383C (OR: 2.32, 95% CI: 1.34-4.01), R1479C/T (OR: 1.96, 95% CI: 1.05-3.64; OR:
      5.15, 95% CI: 2.53-10.48), C1485T (OR: 2.40, 95% CI: 1.41-4.08), C1631T (OR:
      4.09, 95% CI: 1.41-11.85), C1653T (OR: 2.58, 95% CI: 1.59-4.19), G1719T (OR:
      2.11, 95% CI: 1.19-3.73), and T1800C (OR: 23.59, 95% CI: 2.25-247.65) were
      independent risk factors for genotype C HBV-related HCC, presenting different
      trends among individual disease phases. 4) Several genotype C HCC risk mutations
      pre-existed, even as major types, in early disease phases with other genotypes.
      CONCLUSIONS: Mutations associated with HCC risk were mainly located in HBx
      transactivation domain, viral promoter, protein/miRNA binding sites, and the area
      for immune epitopes. Furthermore, the signatures of these mutations were unique
      to disease phases leading to HCC, suggesting molecular counteractions between the
      virus and host during hepatocarcinogenesis.

PMID- 25942598
TI  - Disruption of key GTPase regulators of endocytic recycling compartment does not
      interfere with soluble antigen crosspresentation in dendritic cells.

PMID- 25942597
TI  - Regulatory T cells turn pathogenic.
AB  - Foxp3(+) regulatory T (Treg) cells are considered a sub-lineage of CD4(+) T cells
      that are protective against autoimmunity due to their essential roles in
      maintaining immune homeostasis and self-tolerance. However, Treg cells are
      unstable in vivo in terms of lineage specialization and suppressive function.
      These unstable Treg cells play roles in the pathogenesis of diseases, which cause
      safety concerns regarding human Treg cell therapy. In this review, we highlight
      recent findings that demonstrate the pathogenic conversion of Treg cells in
      different disease models. 

PMID- 25942599
TI  - Therapeutic effects of the artemisinin analog SM934 on lupus-prone MRL/lpr mice
      via inhibition of TLR-triggered B-cell activation and plasma cell formation.
AB  - We previously reported that SM934, a water-soluble artemisinin derivative, was a
      viable treatment in murine lupus models. In the current study, we further
      investigated the therapeutic effects of a modified dosage regimen of SM934 on
      lupus-prone MRL/lpr mice and explored its effects on B cell responses, a central
      pathogenic event in systemic lupus erythematosus (SLE). When orally administered
      twice-daily, SM934 significantly prolonged the life-span of MRL/lpr mice,
      ameliorated the lymphadenopathy symptoms and decreased the levels of serum anti
      nuclear antibodies (ANAs) and of the pathogenic cytokines IL-6, IL-10 and IL-21.
      Furthermore, SM934 treatment restored the B-cell compartment in the spleen of
      MRL/lpr mice by increasing quiescent B cell numbers, maintaining germinal center
      B-cell numbers, decreasing activated B cell numbers and reducing plasma cell (PC)
      numbers. Ex vivo, SM934 suppressed the Toll-like receptor (TLR)-triggered
      activation and proliferation of B cells, as well as antibody secretion. Moreover,
      the present study demonstrated that SM934 interfered with the B-cell intrinsic
      pathway by downregulating TLR7/9 mRNA expression, MyD88 protein expression and NF
      kappaB phosphorylation. In human peripheral blood mononuclear cells (PBMCs),
      consistent with the results in MRL/lpr mice, SM934 inhibited TLR-associated B
      cell activation and PC differentiation. In conclusion, a twice daily dosing
      regimen of SM934 had therapeutic effects on lupus-prone MRL/lpr mice by
      suppressing B cell activation and plasma cell formation.

PMID- 25942600
TI  - Short-term memory of danger signals or environmental stimuli in mesenchymal stem
      cells: implications for therapeutic potential.
AB  - Mesenchymal stem/stromal cells (MSCs) possess some characteristics of immune
      cells, including a pro-inflammatory phenotype, an immunosuppressive phenotype,
      antibacterial properties and the expression of Toll-like receptor proteins. Here
      we show that, similar to immune cells, MSCs retain information from danger
      signals or environmental stimuli for a period of time. When treated with the pro
      inflammatory factors lipopolysaccharide (LPS) or tumor necrosis factor-alpha (TNF
      alpha), MSCs display increased expression of IL-6, IL-8 and MCP-1. Following re
      plating and several rounds of cell division in the absence of stimulating
      factors, the expression of IL-6, IL-8 and MCP-1 remained higher than in untreated
      cells for over 7 days. A spike in cytokine secretion occurred when cells were
      exposed to a second round of stimulation. We primed MSCs with LPS and LPS-primed
      MSCs had better therapeutic efficacy at promoting skin flap survival in a
      diabetic rat model than did unprimed MSCs. Finally, we found that several
      microRNAs, including miR146a, miR150 and miR155, along with the modification of
      DNA by 5-hydroxymethylcytosine (5hmC), mediate the MSC response to LPS and TNF
      alpha stimulation. Collectively, our data suggest that MSCs have a short-term
      memory of environmental signals, which may impact their therapeutic potential.

PMID- 25942601
TI  - A new effect of IL-4 on human gammadelta T cells: promoting regulatory Vdelta1 T
      cells via IL-10 production and inhibiting function of Vdelta2 T cells.
AB  - Interleukin 4 (IL-4) has a variety of immune functions, including helper T-cell
      (Th-cell) differentiation and innate immune-response processes. However, the
      impact of IL-4 on gamma delta (gammadelta) T cells remains unclear. In this
      study, we investigate the effects of IL-4 on the activation and proliferation of
      gammadelta T cells and the balance between variable delta 1 (Vdelta1) and Vdelta2
      T cells in humans. The results show that IL-4 inhibits the activation of
      gammadelta T cells in the presence of gammadelta T-cell receptor (TCR)
      stimulation in a STAT6-dependent manner. IL-4 promoted the growth of activated
      gammadelta T cells and increased the levels of Vdelta1 T cells, which in turn
      inhibited Vdelta2 T-cell growth via significant IL-10 secretion. Vdelta1 T cells
      secreted significantly less interferon gamma (IFNgamma) and more IL-10 relative
      to Vdelta2. Furthermore, Vdelta1 T cells showed relatively low levels of Natural
      Killer Group 2D (NKG2D) expression in the presence of IL-4, suggesting that
      Vdelta1 T cells weaken the gammadelta T cell-mediated anti-tumor immune response.
      For the first time, our findings demonstrate a negative regulatory role of IL-4
      in gammadelta T cell-mediated anti-tumor immunity. 

PMID- 25942602
TI  - Relationship of Intraocular Pressure with Central Aortic Systolic Pressure.
AB  - PURPOSE: To examine the relationship between central aortic systolic pressure
      (CASP) and intraocular pressure (IOP), and to compare the strength of any
      association with that of peripheral blood pressure and IOP. METHODS: Adults
      ranging in age from 40 to 80 years were consecutively recruited from the
      population-based Singapore Chinese Eye Study. We measured CASP using arterial
      tonometry (BPro) and IOP using Goldmann applanation tonometry. All participants
      had a standardized examination including a complete ophthalmic and systemic
      examination. Systolic blood pressure (SBP) and diastolic blood pressure (DBP)
      were measured using peripheral blood pressure cuff. Univariable and multiple
      linear regression analyses were performed to examine the relationship between
      CASP and IOP. Standardized regression coefficients (sbeta) were calculated to
      compare the associations between CASP and SBP with IOP. RESULTS: A total of 372
      consecutive Chinese participants were analyzed. After adjusting for age, gender,
      body mass index, total cholesterol, use of antihypertensive medication and
      central corneal thickness, each 10 mmHg increase in CASP was associated with 0.32
      mmHg of IOP elevation [95% confidence interval (CI): 0.10-0.53, sbeta = 0.160, p
      value = 0.004]. SBP also had a positive relationship with IOP (beta = 0.279, 95%
      CI: 0.079-0.479, sbeta = 0.152, p value = 0.006). Associations between IOP and
      CASP, SBP and DBP were similar in participants using antihypertensive medication
      to participant not using antihypertensives. CONCLUSIONS: Increased CASP, as
      measured by arterial tonometry, is associated with higher IOP. Our results
      strengthen the relationship between systemic blood pressure and IOP.

PMID- 25942603
TI  - Integrated System of Phytodepuration for Agroindustrial Wastewater: Three
      Different Case Studies.
AB  - The effluents deriving from agricultural industries are sources of wastewater
      sensibly different from common civil wastewater treatment plants effluents,
      because they are characterized by significant amounts of nutrients and organic
      load. Agricultural industries require considerable water volumes for processing
      the farm products, in doing so generating huge volumes of wastewater, with high
      concentration of chemical oxygen demand (COD), nitrogen (N) and phosphorus (P).
      Advanced and low cost techniques for water depuration are required in such
      circumstances, as the use of Integrated System of Phytodepuration (ISP). In the
      present work, three different case studies (a dairy, a pig feedlot and a vinegar
      industry) are investigated: the performances of the ISPs were evaluated analyzing
      raw wastewaters and final effluents over a period ranging from 2 to 4 years. The
      results obtained show that the designed ISPs are characterized by a mean
      efficiency value higher than 85% for COD removal, 73% for N and 85% for P.
      Moreover, for the pig feedlot the ISP final effluent is characterized by a
      quality level not only suited for the release into surface waters but also for
      irrigation, while for the other two case studies is possible to release the final
      effluent in surface water. 

PMID- 25942604
TI  - How Cellulose Elongates--A QM/MM Study of the Molecular Mechanism of Cellulose
      Polymerization in Bacterial CESA.
AB  - The catalytic mechanism of bacterial cellulose synthase was investigated by using
      a hybrid quantum mechanics and molecular mechanics (QM/MM) approach. The
      Michaelis complex model was built based on the X-ray crystal structure of the
      cellulose synthase subunits BcsA and BcsB containing a uridine diphosphate
      molecule and a translocating glucan. Our study identified an SN2-type transition
      structure corresponding to the nucleophilic attack of the nonreducing end O4 on
      the anomeric carbon C1, the breaking of the glycosidic bond C1-O1, and the
      transfer of proton from the nonreducing end O4 to the general base D343. The
      activation barrier found for this SN2-type transition state is 68 kJ/mol. The
      rate constant of polymerization is estimated to be ~8.0 s(-1) via transition
      state theory. A similar SN2-type transition structure was also identified for a
      second glucose molecule added to the growing polysaccharide chain, which aligned
      with the polymer 180 degrees  rotated compared to the initially added unit. This
      study provides detailed insights into how cellulose is extended by one glucose
      molecule at a time and how the individual glucose units align into cellobiose
      repeating units. 

PMID- 25942607
TI  -  History of metabolic treatments in burn care.
AB  - This article discusses the recent history of advances in burn care and
      increased understanding that have led to achievements in modulating the metabolic
      response following burn injury and significant improvements in patient outcomes.
      The authors describe the development of pharmacological and nonpharmacological
      strategies to modulate post-burn metabolism and the catabolic response. 

PMID- 25942606
TI  - Safety and efficacy of oxycodone/naloxone vs. oxycodone vs. morphine for the
      treatment of chronic low back pain: results of a 12 week prospective, randomized,
      open-label blinded endpoint streamlined study with prolonged-release
      preparations.
AB  - BACKGROUND: Opioid-induced constipation (OIC) is the most prevalent patient
      complaint associated with opioid use and interferes with analgesic efficacy.
      OBJECTIVES: This PROBE trial compares the overall safety and tolerability of
      oxycodone/naloxone (OXN) with those of traditional opioid therapy with oxycodone
      (OXY) or morphine (MOR) in the setting of the German healthcare system. RESEARCH
      DESIGN AND METHODS: This was a prospective, randomized, open-label, blinded
      endpoint (PROBE) streamlined study (German pain study registry: 2012-0012-05;
      EudraCT: 2012-001317-16), carried out in 88 centers in Germany, where a total of
      453 patients, requiring WHO step III opioids to treat low back pain, were
      randomized to OXN, OXY or MOR (1:1:1) for 3 months. The primary outcome was the
      percentage of patients without adverse event-related study discontinuations who
      presented with a combination of a >=50% improvement of pain intensity, disability
      and quality-of-life and a <=50% worsening of bowel function at study end.
      RESULTS: Significantly more OXN patients met the primary endpoint (22.2%) vs. OXY
      (9.3%; OR: 2.80; p < 0.001) vs. MOR (6.3%; OR: 4.23; p < 0.001), with
      insignificant differences between OXY vs. MOR (p = 0.155). A >=50% improvement of
      pain intensity, functional disability and quality-of-life has been found for OXN
      in 75.0/61.1/66.0% of patients and thus for all parameters significantly more
      than with OXY (58.9/49.0/48.3; p < 0.001 for each) or MOR (52.5/46.2/37.3; p <
      0.001 for each). A total of 86.8% of OXN patients kept normal BFI scores during
      treatment, vs. 63.6% for OXY (p < 0.001) vs. 53.8% for MOR (p < 0.001). Overall
      189 TEAEs (OXN: 45, OXY: 69, MOR: 75) in 92 patients (OXN: 21, OXY: 44, MOR: 37)
      occurred, most gastrointestinal (50.8%). One limitation is the open-label design,
      which presents the possibility of interpretive bias. CONCLUSION: Under the
      conditions of this PROBE design, OXN was associated with a significantly better
      tolerability, a lower risk of OIC and a significantly better analgesic efficacy
      than OXY or MOR.

PMID- 25942605
TI  - Heme Degradation by Heme Oxygenase Protects Mitochondria but Induces ER Stress
      via Formed Bilirubin.
AB  - Heme oxygenase (HO), in conjunction with biliverdin reductase, degrades heme to
      carbon monoxide, ferrous iron and bilirubin (BR); the latter is a potent
      antioxidant. The induced isoform HO-1 has evoked intense research interest,
      especially because it manifests anti-inflammatory and anti-apoptotic effects
      relieving acute cell stress. The mechanisms by which HO mediates the described
      effects are not completely clear. However, the degradation of heme, a strong pro
      oxidant, and the generation of BR are considered to play key roles. The aim of
      this study was to determine the effects of BR on vital functions of hepatocytes
      focusing on mitochondria and the endoplasmic reticulum (ER). The affinity of BR
      to proteins is a known challenge for its exact quantification. We consider two
      major consequences of this affinity, namely possible analytical errors in the
      determination of HO activity, and biological effects of BR due to direct
      interaction with protein function. In order to overcome analytical bias we
      applied a polynomial correction accounting for the loss of BR due to its
      adsorption to proteins. To identify potential intracellular targets of BR we used
      an in vitro approach involving hepatocytes and isolated mitochondria. After
      verification that the hepatocytes possess HO activity at a similar level as liver
      tissue by using our improved post-extraction spectroscopic assay, we elucidated
      the effects of increased HO activity and the formed BR on mitochondrial function
      and the ER stress response. Our data show that BR may compromise cellular
      metabolism and proliferation via induction of ER stress. ER and mitochondria
      respond differently to elevated levels of BR and HO-activity. Mitochondria are
      susceptible to hemin, but active HO protects them against hemin-induced toxicity.
      BR at slightly elevated levels induces a stress response at the ER, resulting in
      a decreased proliferative and metabolic activity of hepatocytes. However, the
      proteins that are targeted by BR still have to be identified. 

PMID- 25942608
TI  -  Topical antimicrobials in burn wound care: a recent history    .
AB  - "It is nearly 100 years since antisepsis came to dominate the treatment of
      burns. All that has been accomplished, as far as we can see from the data
      available, has been to offset the good that sound physiological and surgical
      principles and modern aseptic technique should have afforded."1 Carl A. Moyer,
      MD, 1954    . 

PMID- 25942609
TI  -  Skin substitutes in burn care .
AB  - The history on the use of graft material aside from skin for both partial-
      and full-thickness burns was sought. METHODS: Medline and Google searches were
      performed using the key words: skin graft, skin substitute, allograft, homograft,
      xenograft, heterograft, autograft, burn grafting, and burn coverage. Articles
      retrieved were visually scanned for applicability and those thought to apply were
      reviewed as were appropriate references obtained within the articles. CONCLUSION:
      There have been several technological advances in the grafting of burns with
      synthetic materials, but autograft remains the standard to which all other graft
      resources must be compared.

PMID- 25942610
TI  - From cholera to "fluid creep": a historical review of fluid resuscitation of the
      burn trauma patient.
AB  - Resuscitation of the burn trauma patient presents unique dynamic challenges,
      which often involve the critical care management of multiple physiological
      derangements. It is well known that a major burn injury can lead to burn shock
      and involve multiple organ systems. Fluid resuscitation is the mainstay in
      prevention of burn shock and for initial stabilization. To date, many studies
      have focused on the importance of fluid resuscitation in the treatment of burn
      patients; however, there is no one universally accepted model for intravenous
      fluid therapy. Certainly, monumental advances have been made in burn
      resuscitation, which have lead to dramatically decreased mortality rates and
      virtually eliminated post-burn renal failure. The early work of Cope and Moore,
      Evans, Artz, Moyer, Baxter, Pruitt, and others have served us well and continue
      to drive modern fluid resuscitation. Which formula is most appropriate and which
      fluid, or combination of fluids, is most advantageous continues to be debated
      today. Regardless of which formula is used, it is clear that continuous
      individual titration of volume must be made according to the patients clinical
      response to avoid the detrimental problems associated with both over
      resuscitation and under resuscitation. 

PMID- 25942611
TI  -  A brief historical review of flaps and burn reconstruction.
AB  - Thermal, chemical, and electrical injuries contribute to some of the most
      disabling and deforming wound injury patterns. These challenges, ultimately cared
      for by burn and reconstructive specialists, require an evolution in the
      understanding of functional and aesthetic prioritization, 3-dimensional geometric
      rearrangement of tissues, anatomic considerations of neurovascularized
      constructs, as well as the development of fundamental technical skills. Flaps,
      generally defined as tissue constructs, transferred along with a defined vascular
      supply are considered principle elements in the armamentarium of the
      reconstructive specialist. The transfer and design of these flaps can augment
      most tissue type deficits, protect or transfer functional neurovascular and
      musculotendinous structures, and provide bone and durable soft tissue elements to
      restore both form and function. The history of flap construct and reconstruction
      precedes available written text and spans independent cultural, temporal and
      geographic divides. Several key flaps currently utilized in burn and
      reconstructive surgery will be reviewed with some historical context provided. A
      comprehensive review of the history of flaps in reconstructive surgery certainly
      exceeds the scope of any simplistic chapter or text. 

PMID- 25942612
TI  -  Skin grafting in burns    .
AB  - The purpose of this article is to review the history of skin grafting in burn
      injuries. A Medline and Google search were performed on the key words, skin
      graft, autograft, allograft, xenograft, burn surgery, burn excision, and burn
      grafting. The articles were reviewed and the additional references were provided
      by the bibliographies of these articles, which were also reviewed. The history of
      skin grafting in burn injury is traced from before the birth of Christ to present
      day. The first publication of successful skin grafts for wounds was authored by
      Swiss surgeon J.L. Reverdin in 1869. Progression in graft improvement was slow.
      The 1930s brought mechanical dermatomes into practice, while the mechanical
      mesher was not introduced until the 1960s. Finally, the practice of early
      excision and grafting, which is the cornerstone of burn care today, became common
      practice. 

PMID- 25942613
TI  - Automated Scalable Heat Shock Modification for Standard Aquatic Housing Systems.
AB  - Heat shock is a common technique for inducible gene expression system in a
      variety of organisms. Heat shock treatment of adult zebrafish is more involved
      and generally consists of manually transferring fish between housing rack tanks
      and preheated water tanks or the use of timed heaters in stand-alone aquaria. To
      avoid excessive fish handling and to take advantage of the continuous flow of a
      standard housing rack, proposed modifications consisted of installing an aquarium
      heater inside each tank, manually setting the heater to reach heat shocking
      temperatures (> 37 degrees C) and, after that, testing that every tank responded
      equally. To address the limitations in the existing systems, we developed a novel
      modification of standard zebrafish housing racks to perform heat shock treatment
      in conditions of continuous water flow. By adding an extra manifold to the
      housing rack and connecting it to a recirculating bath to create a parallel water
      flow system, we can increase the temperature from standard conditions (28.5
      degrees C) to heat shock conditions with high precision (38.0-38.3 degrees C,
      mean +/- SD = 38.1 degrees C +/- 0.14 degrees C) and minimal variation among
      experimental tanks (coefficient of variation [CV] = 0.04%). This means that there
      is virtually no need for laborious pretreatment calibrations or continuous
      adjustments to minimize intertank variation. To test the effectiveness of our
      design, we utilized this system to induce enhanced green fluorescent protein
      (EGFP) expression in hsp70-EGFP fish and performed a fin regeneration experiment
      with hsp70l:dnfgfr1-EGFP fish to confirm that heat-induced gene expression
      reached physiological levels. In summary, our newly described aquatic heat shock
      system minimizes effort during heat shock experiments, while ensuring the best
      water quality and fish welfare and facilitating large heat shock settings or the
      use of multiple transgenic lines for both research and teaching experiments.

PMID- 25942614
TI  - Selective Probing of the Penetration of Dexamethasone into Human Skin by Soft X
      ray Spectromicroscopy.
AB  - Selective probing of dexamethasone in excised human skin using soft X-ray
      spectromicroscopy provides quantitative concentration profiles as well as two
      dimensional drug distribution maps. Element- and site-selective excitation of
      dexamethasone at the oxygen K-edge with the lateral step width adjusted to 1 MUm
      provides detailed information on the location of the drug in the different skin
      layers. The key of this work is to probe dexamethasone selectively at the
      carbonyl site (C3) by the O 1s -> pi* transition, providing also a most efficient
      way to quantify the drug concentration as a function of penetration depth in
      correlation with structural properties of the skin containing carboxyl and amide
      oxygen sites occurring at higher transition energy than dexamethasone. Following
      drug exposure for 4 h, the glucocorticoide is located in about equal amounts in
      the stratum corneum, the outermost horny layer of skin, and in the viable
      epidermis, whereas in the dermis no dexamethasone is detected. In the stratum
      corneum, most of the lipophilic drug is found in regions between corneocytes,
      where epidermal lipids are dominating. 

PMID- 25942616
TI  - Highly Efficient Photoelectrochemical Hydrogen Generation Using Zn(x)Bi2S(3+x)
      Sensitized Platelike WO3 Photoelectrodes.
AB  - Zn(x)Bi2S(3+x) sensitized platelike WO3 photoelectrodes on FTO substrates were
      for the first time prepared via a sequential ionic layer adsorption reaction
      (SILAR) process. The samples were characterized by scanning electron microscopy
      (SEM), transmission electron microscopy (TEM), ultraviolet visible spectrometry
      (UV-vis), and Raman spectra. The results show that the ZnxBi2S3+x quantum dots
      (QDs) are uniformly coated on the entire surface of WO3 plates, forming a
      WO3/Zn(x)Bi2S(3+x) core/shell structure. The Zn(x)Bi2S(3+x)/WO3 films show a
      superior ability to capture visible light. High-efficiency photoelectrochemical
      (PEC) hydrogen generation is demonstrated using the prepared electrodes as
      photoanodes in a typical three-electrode electrochemical cell. Compared to the
      Bi2S3/WO3 photoelectrodes, the Zn(x)Bi2S(3+x)/WO3 photoelectrodes exhibit good
      photostability and excellent PEC activity, and the photocurrent density is up to
      7.0 mA cm(-2) at -0.1 V versus Ag/AgCl under visible light illumination.
      Investigation of the electron transport properties of the photoelectrodes shows
      that the introduction of ZnS enhances the photoelectrons' transport rate in the
      photoelectrode. The high PEC activity demonstrates the potential of the
      Zn(x)Bi2S(3+x)/WO3 film as an efficient photoelectrode for hydrogen generation.

PMID- 25942615
TI  - Role of chromatin structure modulation by the histone deacetylase inhibitor
      trichostatin A on the radio-sensitivity of ataxia telangiectasia.
AB  - At present, a lot is known about biochemical aspects of double strand breaks
      (DBS) repair but how chromatin structure affects this process and the sensitivity
      of DNA to DSB induction is still an unresolved question. Ataxia telangiectasia (A
      T) patients are characterised by very high sensitivity to DSB-inducing agents
      such as ionising radiation. This radiosensitivity is revealed with an enhancement
      of chromosomal instability as a consequence of defective DNA repair for a small
      fraction of breaks located in the heterochromatin, where they are less
      accessible. Besides, recently it has been reported that Ataxia Telangiectasia
      Mutated (ATM) mediated signalling modifies chromatin structure. In order to study
      the impact of chromatin compaction on the chromosomal instability of A-T cells,
      the response to trichostatin-A, an histone deacetylase inhibitor, in normal and A
      T lymphoblastoid cell lines was investigated testing its effect on chromosomal
      aberrations, cell cycle progression, DNA damage and repair after exposure to X
      rays. The results suggest that the response to both trichostatin-A pre- and
      continuous treatments is independent of the presence of either functional or
      mutated ATM protein, as the reduction of chromosomal damage was found also in the
      wild-type cell line. The presence of trichostatin-A before exposure to X-rays
      could give rise to prompt DNA repair functioning on chromatin structure already
      in an open conformation. Differently, trichostatin-A post-treatment causing
      hyperacetylation of histone tails and reducing the heterochromatic DNA content
      might diminish the requirement for ATM and favour DSBs repair reducing
      chromosomal damage only in A-T cells. This fact could suggest that trichostatin-A
      post-treatment is favouring the slow component of DSB repair pathway, the one
      impaired in absence of a functionally ATM protein. Data obtained suggest a
      fundamental role of chromatin compaction on chromosomal instability in A-T cells.

PMID- 25942617
TI  - Prevalence of Listeria spp. and Molecular Characterization of Listeria
      monocytogenes Isolates from Broilers at the Abattoir.
AB  - Products from three broiler abattoirs were sampled for Listeria species to
      evaluate the changes in the prevalence and contamination rates at two stages of
      processing. Sampling was performed at the evisceration stage and at the end of
      processing after packaging and refrigerating at 4 degrees C for 24 h. A total of
      212 samples were collected; 52 were from abattoir A, and 80 samples each were
      collected from abattoirs B and C. Among all samples, 99 (46.7%) tested positive
      for Listeria, including L. monocytogenes 19 (8.9%), L. innocua 69 (32.5%), L.
      grayi 10 (4.7%), and L. welshimeri 1 (0.5%). The L. monocytogenes contamination
      rate varied from 5% to 11.5% in the 3 abattoirs. L. innocua was the most common
      species identified and was found in 8.8% of the samples from abattoir A and 33.7%
      of the samples from both abattoirs B and C. Twenty-six of the L. monocytogenes
      isolates obtained from positive samples were subjected to serotyping by multiplex
      polymerase chain reaction and characterization by the pulsed-field gel
      electrophoresis (PFGE) method using two cutting enzymes, ApaI and AscI. Three
      molecular serogroups were identified: IIa, IIb, and IVb. Serogroup IIa was common
      to all abattoirs, and serogroups IIb and IVb were found only in abattoir C. The
      10 different obtained PFGE profiles were grouped into 7 clusters; some of these
      clusters were common to the 3 abattoirs, and others were specific to the
      abattoirs in which they were identified. This study revealed a high prevalence of
      Listeria spp., particularly L. monocytogenes, in raw broilers. This high
      incidence presents a risk to consumers due to the potential occurrence of cross
      contamination with other foods in domestic refrigerators and the ability of these
      microorganisms to survive in undercooked products. 

PMID- 25942618
TI  - Facile one-step photolithographic method for engineering hierarchically
      nano/microstructured transparent superamphiphobic surfaces.
AB  - It is of great value to develop a simple, controllable, and scalable method of
      making superamphiphobic surfaces. Here we present a facile one-step
      photolithographic method to engineer superamphiphobic surfaces consisting of
      photoresist micropillars decorated with nanoparticles of the same photoresist.
      The surface or coating is optically transparent and versatile, and can be
      fabricated on a broad range of substrates including stretchable elastomers.
      During the development of the micropillar array, photoresist nanoparticles are
      spontaneously grown on the micropillars by a well-controlled emulsification
      process of the un-cross-linked residual photoresist. This creates a hierarchical
      structure with a re-entrant and convex morphology which is the key for
      superoleophobicity. The chemical bonding between the nanoparticles and the
      micropillars is strong producing a robust and durable coating. This facile method
      is scalable and industry-applicable for a variety of applications such as self
      cleaning, antifouling, and deicing/antifrosting. 

PMID- 25942619
TI  - Vascular development for climate control.
AB  - Early anatomists noted the close juxtaposition of arteries and veins, which
      modern physiologists proposed aided temperature regulation. In this issue of
      Developmental Cell, Kidoya and colleagues (2015) demonstrate that the secreted
      protein Apelin and hematopoietic-endothelial cell interactions create this
      arrangement, providing genetic evidence for its function as a heat-exchange
      mechanism. 

PMID- 25942620
TI  - Mitotic spindle orientation: semaphorin-plexin signaling flags the way.
AB  - The extracellular signals and corresponding receptors that align the mitotic
      spindle of symmetrically dividing cells within an epithelial sheet are largely
      unknown. In this issue of Developmental Cell, Xia et al. (2015) identify
      semaphorin-plexin signaling as a regulator of spindle orientation critical for
      kidney development and repair.

PMID- 25942621
TI  - Stress Relief Downstream of TOR.
AB  - Reduced activity of the growth-regulating TOR complex 1 induces transcription of
      many genes. In this issue of Developmental Cell, Tiebe et al. (2015) identify a
      transcriptional regulator complex repressed by TORC1 and responsible for a vast
      majority of the observed transcriptional changes in Drosophila.

PMID- 25942622
TI  - Nuclear pore basket proteins are tethered to the nuclear envelope and can
      regulate membrane curvature.
AB  - Nuclear pore complexes (NPCs) are selective transport channels embedded in the
      nuclear envelope. The cylindrical NPC core forms a protein coat lining a highly
      curved membrane opening and has a basket-like structure appended to the
      nucleoplasmic side. How NPCs interact with lipids, promoting membrane bending and
      NPC integrity, is poorly understood. Here we show that the NPC basket proteins
      Nup1 and Nup60 directly induce membrane curvature by amphipathic helix insertion
      into the lipid bilayer. In a cell-free system, both Nup1 and Nup60 transform
      spherical liposomes into highly curved membrane structures. In vivo, high levels
      of the Nup1/Nup60 amphipathic helices cause deformation of the yeast nuclear
      membrane, whereas adjacent helical regions contribute to anchoring the basket to
      the NPC core. Basket amphipathic helices are functionally linked to distinct
      transmembrane nucleoporins of the NPC core, suggesting a key contribution to the
      membrane remodeling events that underlie NPC assembly.

PMID- 25942623
TI  - DNA Sequence-Specific Binding of CENP-B Enhances the Fidelity of Human Centromere
      Function.
AB  - Human centromeres are specified by a stably inherited epigenetic mark that
      maintains centromere position and function through a two-step mechanism relying
      on self-templating centromeric chromatin assembled with the histone H3 variant
      CENP-A, followed by CENP-A-dependent nucleation of kinetochore assembly.
      Nevertheless, natural human centromeres are positioned within specific megabase
      chromosomal regions containing alpha-satellite DNA repeats, which contain binding
      sites for the DNA sequence-specific binding protein CENP-B. We now demonstrate
      that CENP-B directly binds both CENP-A's amino-terminal tail and CENP-C, a key
      nucleator of kinetochore assembly. DNA sequence-dependent binding of CENP-B
      within alpha-satellite repeats is required to stabilize optimal centromeric
      levels of CENP-C. Chromosomes bearing centromeres without bound CENP-B, including
      the human Y chromosome, are shown to mis-segregate in cells at rates several-fold
      higher than chromosomes with CENP-B-containing centromeres. These data
      demonstrate a DNA sequence-specific enhancement by CENP-B of the fidelity of
      epigenetically defined human centromere function. 

PMID- 25942625
TI  - Zeb family members and boundary cap cells underlie developmental plasticity of
      sensory nociceptive neurons.
AB  - Dorsal root ganglia (DRG) sensory neurons arise from heterogeneous precursors
      that differentiate in two neurogenic waves, respectively controlled by Neurog2
      and Neurog1. We show here that transgenic mice expressing a Zeb1/2 dominant
      negative form (DBZEB) exhibit reduced numbers of nociceptors and altered pain
      sensitivity. This reflects an early impairment of Neurog1-dependent neurogenesis
      due to the depletion of specific sensory precursor pools, which is slightly later
      partially compensated by the contribution of boundary cap cells (BCCs). Indeed,
      combined DBZEB expression and genetic BCCs ablation entirely deplete second wave
      precursors and, in turn, nociceptors, thus recapitulating the Neurog1(-/-)
      neuronal phenotype. Altogether, our results uncover roles for Zeb family members
      in the developing DRGs; they show that the Neurog1-dependent sensory neurogenesis
      can be functionally partitioned in two successive phases; and finally, they
      illustrate plasticity in the developing peripheral somatosensory system supported
      by the BCCs, thereby providing a rationale for sensory precursor diversity.

PMID- 25942624
TI  - A family of tetraspans organizes cargo for sorting into multivesicular bodies.
AB  - The abundance of cell-surface membrane proteins is regulated by internalization
      and delivery into intralumenal vesicles (ILVs) of multivesicular bodies (MVBs).
      Many cargoes are ubiquitinated, allowing access to an ESCRT-dependent pathway
      into MVBs. Yet how nonubiquitinated proteins, such as
      glycosylphosphatidylinositol-anchored proteins, enter MVBs is unclear, supporting
      the possibility of mechanistically distinct ILV biogenesis pathways. Here we show
      that a family of highly ubiquitinated tetraspan Cos proteins provides a Ub signal
      in trans, allowing sorting of nonubiquitinated MVB cargo into the canonical ESCRT
      and Ub-dependent pathway. Cos proteins create discrete endosomal subdomains that
      concentrate Ub cargo prior to their envelopment into ILVs, and the activity of
      Cos proteins is required not only for efficient sorting of canonical Ub cargo but
      also for sorting nonubiquitinated cargo into MVBs. Expression of these proteins
      increases during nutrient stress through an NAD(+)/Sir2-dependent mechanism that
      in turn accelerates the downregulation of a broad range of cell-surface proteins.

PMID- 25942627
TI  - Diagnostic Yield and Clinical Implications of Preoperative Upper Gastrointestinal
      Endoscopy in Morbidly Obese Patients Undergoing Bariatric Surgery.
AB  - BACKGROUND AND AIMS: Upper gastrointestinal (UGI) endoscopy in patients
      undergoing bariatric surgery is controversial. It is recommended routinely by
      some authors to detect benign or malignant pathology that mostly remains
      asymptomatic. Others recommend selective use, suggesting not much impact on
      surgical management of detected pathology, especially in asymptomatic patients.
      The aim of this study was to evaluate the diagnostic yield and impact of
      pathological findings on routine UGI endoscopy before bariatric surgery in a
      cohort of morbidly obese Indian patients. MATERIALS AND METHODS: We
      retrospectively reviewed preoperative screening UGI endoscopy reports of 283
      patients who underwent bariatric surgery from February 2012 to August 2014. Data
      were collected on clinical information, UGI endoscopic findings, Helicobacter
      pylori testing, and management. RESULTS: Ten patients gave a history of
      gastroesophageal reflux, and the rest had no specific UGI complaints. Fifty-four
      had no abnormal findings. One hundred ninety-six had a lax lower esophageal
      hiatus, hiatal hernias of <5 cm, Grade I-II esophagitis, or mild to moderate
      gastritis or duodenitis that did not have an impact on surgery. Thirty-one had
      severe erosive gastritis or duodenitis, or polyposis that delayed surgery for
      treatment and review of biopsies. A large hiatal hernia >5 cm changed surgical
      plan to Roux-en-Y gastric bypass from a sleeve gastrectomy in 2 cases. None had
      varices or malignancy. CONCLUSIONS: Preoperative UGI endoscopy yielded a high
      proportion of endoscopic abnormalities even in asymptomatic patients. Surgery was
      delayed to treat severe mucosal lesions and to investigate polypoidal findings in
      the majority. A change in surgical approach and surveillance for malignancy was
      needed in a few cases.

PMID- 25942626
TI  - Endogenously tagged rab proteins: a resource to study membrane trafficking in
      Drosophila.
AB  - Membrane trafficking is key to the cell biological mechanisms underlying
      development. Rab GTPases control specific membrane compartments, from core
      secretory and endocytic machinery to less-well-understood compartments. We tagged
      all 27 Drosophila Rabs with YFP(MYC) at their endogenous chromosomal loci,
      determined their expression and subcellular localization in six tissues
      comprising 23 cell types, and provide this data in an annotated, searchable image
      database. We demonstrate the utility of these lines for controlled knockdown and
      show that similar subcellular localization can predict redundant functions. We
      exploit this comprehensive resource to ask whether a common Rab compartment
      architecture underlies epithelial polarity. Strikingly, no single arrangement of
      Rabs characterizes the five epithelia we examine. Rather, epithelia flexibly
      polarize Rab distribution, producing membrane trafficking architectures that are
      tissue- and stage-specific. Thus, the core machinery responsible for epithelial
      polarization is unlikely to rely on polarized positioning of specific Rab
      compartments.

PMID- 25942628
TI  - InAs/GaAs Sharply Defined Axial Heterostructures in Self-Assisted Nanowires.
AB  - We present the fabrication of axial InAs/GaAs nanowire heterostructures on
      silicon with atomically sharp interfaces by molecular beam epitaxy. Our method
      exploits the crystallization at low temperature, by As supply, of In droplets
      deposited on the top of GaAs NWs grown by the self-assisted (self-catalyzed)
      mode. Extensive characterization based on transmission electron microscopy sets
      an upper limit for the InAs/GaAs interface thickness within few bilayers (<=1.5
      nm). A detailed study of elastic/plastic strain relaxation at the interface is
      also presented, highlighting the role of nanowire lateral free surfaces. 

PMID- 25942629
TI  - Correlates of Child Maltreatment Among Adolescent Mothers With Young Children.
AB  - Child maltreatment and teen pregnancy are serious social problems facing America
      today. In 2010, 3.3 million referrals of child abuse and neglect resulted in
      approximately 461,297 confirmed victims. Teen pregnancy has similarly been a
      cause of serious political and social concern. Although the teen birth rate has
      declined overall during the last half century, the United States still has a
      higher teen birth rate than other industrialized countries. Young maternal age is
      generally considered a risk factor for child maltreatment. What is not known is
      what separates adolescent mothers who maltreat their children and those who do
      not. This study compares the ecological correlates of adolescent mothers who
      maltreat their children to adolescent mothers who do not maltreat. Implications
      for practice and future research are discussed. 

PMID- 25942630
TI  - Risk factors for glioblastoma therapy associated complications.
AB  - OBJECTIVE: Thromboembolic events, seizures, neurologic symptoms and adverse
      effects from corticosteroids and chemotherapies are frequent clinical
      complications seen in Glioblastoma (GB) patients. The exact impact these have on
      dismal patient outcome has not been fully elucidated. We aimed at assessing
      treatment associated complications, evaluating the impact on survival and
      defining risk factors. METHODS: Two hundred and thirty three consecutive adult
      patients operated on for newly diagnosed GB at a single tertiary institution over
      a 5-year-period (2006-2011) were assessed. Demographic parameters (age, gender,
      comorbidity status quantified by the Charlson-comorbidity-index (CCI), functional
      status computed by the Karnofsky Performance Scale (KPS), tumor characteristics
      (size, location, IDH-1 mutation and MGMT-Promotor-methylation-status) and
      treatment parameters (volumetrically quantified extent of resection and adjuvant
      therapy) were retrospectively reviewed. Complications assessed were recorded as
      neurological (N), surgical (S) and medical (M). Independent risk factor analysis
      was performed by the univariate and multivariate logistic regression method.
      Survival analysis was plotted by the Kaplan-Meier-method, influence of
      complication occurrence was evaluated by the log-rank test. RESULTS: One hundred
      and fifty nine (68.2%) patients had a total of 281 complications (90 N, 174 M and
      17 S). Univariate analysis identified age (P=0.003), KPS<70 (P=0.002), CCI>3
      (P=0.03), eloquent tumor location (P=0.001) and therapy other than the standard
      radio-chemotherapy with temozolomide therapy (P=0.034) as risk factors for
      complications. Multivariate analysis extracted the eloquent tumor location
      (P=0.007, odds ratio 1.94) as a significant predictor for complications. Having a
      complication significantly decreased patient survival (P=0.015). CONCLUSIONS:
      Complications significantly decrease GB patient survival. Age, poor functional
      status, other than standard adjuvant therapy and eloquent tumor location proved
      as significant risk factors for encountering a therapy associated complication.
      Not extensive surgery or tumor size but surgery at eloquent locations impacts
      complication occurrence the strongest with a 2 fold increased complication
      occurrence risk.

PMID- 25942631
TI  - Ultrasound-guided percutaneous microwave ablation for adenomyosis: efficacy of
      treatment and effect on ovarian function.
AB  - A total of 142 premenopausal women with symptomatic adenomyosis underwent
      ultrasound (US)-guided percutaneous microwave ablation (PMWA) at the Chinese PLA
      General Hospital. This study aimed to evaluate changes in serum pituitary,
      gonadal hormone and cancer antigen 125 (CA125) levels after US-guided PMWA.
      Therefore, estradiol (E2), follicle-stimulating hormone (FSH), prolactin (PRL)
      and CA125 levels were evaluated before ablation and at 3, 6, 9 and 12 months
      after ablation. No significant differences were observed in the E2 and FSH levels
      pre-ablation and during follow-up (E2: p=0.933, p=0.987, p=0.106, p=0.936; FSH:
      p=0.552, p=0.295, p=0.414, p=0.760). The mean absolute values of serum CA125 and
      PRL were significantly decreased at 3, 6, 9 and 12 months after ablation (CA125:
      p<0.001, p<0.001, p<0.001, p=0.003; PRL: p<0.001, p<0.001, p<0.001, p<0.001). A
      significant correlation between changes in CA125 levels and uterine volume was
      found (p<0.001). No evidence of a decline in ovarian function was observed after
      US-guided PMWA.

PMID- 25942632
TI  - The kinetics of blood lactate in boys during and following a single and repeated
      all-out sprints of cycling are different than in men.
AB  - This study characterized the impact of high-intensity interval training on the
      kinetics of blood lactate and performance in trained boys and men. Twenty-one
      boys (11.4 +/- 0.8 years) and 19 men (29.4 +/- 5.0 years) performed a set of four
      30-s sprints with 2-min of rest and a single 30-s sprint on 2 separate occasions
      (randomized order) with assessment of performance. Blood lactate was assayed
      after each sprint and during 30 min of recovery from both tests. The individual
      time-curves of blood lactate concentration were fitted to the biexponential
      function as follows: [Formula: see text], where the velocity parameters gamma1
      and gamma2 reflect the capacity to release lactate from the previously active
      muscle into the blood and to subsequently eliminate lactate from the organism,
      respectively. In both tests, peak blood lactate concentration was significantly
      lower in the boys (four 30-s sprints: 12.2 +/- 3.6 mmol.L(-1); single 30-s
      sprint: 8.7 +/- 1.8 mmol.L(-1)) than men (four 30-s sprints: 16.1 +/- 3.3 mmol.L(
      1); single 30-s sprint: 11.5 +/- 2.1; p < 0.001). The boys exhibited faster
      gamma1 (1.4531 +/- 0.65 min; p < 0.001) and gamma2 (0.059 +/- 0.023 min; p =
      0.01) in the single 30-s sprint and faster gamma2 (0.049 +/- 0.016 min; p = 0.01)
      in the four 30-s sprints. The worsening of performance from the first to the last
      of the four 30-s sprints was less pronounced in boys (9.2% +/- 13.9%) than men
      (19.2% +/- 11.5%; p = 0.01). In the present study boys, when compared with men,
      exhibited lower Peak blood lactate concentration; less pronounced decline in
      performance during the sprints concomitantly with more rapid release and
      elimination during the single 30-s sprint; and faster elimination of lactate
      following the four 30-s sprints. 

PMID- 25942634
TI  - An Italian population-based case-control study on the association between farming
      and cancer: Are pesticides a plausible risk factor?
AB  - This population-based case-control study investigated the association between
      farming (a proxy for pesticide exposure) and cancer in the Vercelli suburban area
      (northwest Italy). The residents, aged 25 to 79 years, in the above-mentioned
      area during the period 2002-2009 were considered. Cases were all the first
      hospital admissions for cancer. Controls were all the subjects not included in
      the cases and not excluded from the study. Cases and controls were classified
      according to whether they occupationally resulted farmers or nonfarmers during
      the period 1965-2009. Cancer odds ratios (ORs) between farmers and nonfarmers
      were calculated with generalized linear mixed models adjusted by gender and age.
      Farmers showed higher odds for all cancers (OR=1.459; p < .001), nonmelanoma skin
      cancer, colorectal cancer, and breast cancer. The results suggest a plausible
      association between pesticide exposure and cancer occurrence.

PMID- 25942633
TI  - Composition of Plant Sterols and Stanols in Supplemented Food Products.
AB  - All fruits, vegetables, grains and other plant materials contain small amounts of
      plant sterols, which are essential for the function of the biological membranes
      in living cells. The average human consumption of plant sterols has been
      estimated to be about 150-350 mg/day and trace amounts of stanols (which are
      defined as saturated sterols such as sitostanol), but this number varies
      regionally and is higher for vegetarians. When consumed in the diet, plant
      sterols reduce the levels of serum cholesterol. In 1995 the first functional food
      product, Benecol spread (enriched in plant stanol fatty acid esters), was
      developed by Raisio and marketed, first in Finland and then globally. Since then
      many other functional food products have been developed and are now available
      globally. In addition to stanol esters, other functional food products contain
      plant sterol esters and/or free (unesterified) plant sterols and stanols. In
      essentially all of the current functional foods that are enriched in sterols and
      stanols, the feedstock from which the sterols and stanols are obtained is either
      tall oil (a byproduct/coproduct of the pulping of pine wood) or vegetable oil
      deodorizer distillate (a byproduct/coproduct of the refining of vegetable oils).

PMID- 25942635
TI  - The histone H3 N-terminal tail: a computational analysis of the free energy
      landscape and kinetics.
AB  - Histone tails are the short peptide protrusions outside of the nucleosome core
      particle and they play a critical role in regulating chromatin dynamics and gene
      activity. A histone H3 N-terminal tail, like other histone tails, can be
      covalently modified on different residues to activate or repress gene expression.
      Previous studies have indicated that, despite its intrinsically disordered
      nature, the histone H3 N-terminal tail has regions of notable secondary
      structural propensities. To further understand the structure-dynamics-function
      relationship in this system, we have carried out 75.6 MUs long implicit solvent
      simulations and 29.3 MUs long explicit solvent simulations. The extensive
      samplings allow us to better characterize not only the underlying free energy
      landscape but also kinetic properties through Markov state models (MSM). Dihedral
      principal component analysis (dPCA) and locally scaled diffusion map (LSDMap)
      analysis yield consistent results that indicate an overall flat free energy
      surface with several shallow basins that correspond to conformations with a high
      alpha-helical propensity in two regions of the peptide. Kinetic information
      extracted from Markov state models reveals rapid transitions between different
      metastable states with mean first passage times spanning from several hundreds of
      nanoseconds to hundreds of microseconds. These findings shed light on how the
      dynamical nature of the histone H3 N-terminal tail is related to its function.
      The complementary nature of dPCA, LSDMap and MSM for the analysis of biomolecules
      is also discussed. 

PMID- 25942636
TI  - DNA Vaccine Encoding the Chimeric Form of Schistosoma mansoni Sm-TSP2 and Sm29
      Confers Partial Protection against Challenge Infection.
AB  - Schistosomiasis is an important parasitic disease worldwide that affects more
      than 207 million people in 76 countries and causes approximately 250,000 deaths
      per year. The best long-term strategy to control schistosomiasis is through
      immunization combined with drug treatment. Due to the ability of DNA vaccines to
      generate humoral and cellular immune responses, such vaccines are considered a
      promising approach against schistosomiasis. Sm29 and tetraspanin-2 (Sm-TSP2) are
      two proteins that are located in the S. mansoni tegument of adult worms and
      schistosomula and induce high levels of protection through recombinant protein
      immunization. In this study, we transfected BHK-21 cells with plasmids encoding
      Sm29, Sm-TSP2 or a chimera containing both genes. Using RT-PCR analysis and
      western blot, we confirmed that the DNA vaccine constructs were transcribed and
      translated, respectively, in BHK-21 cells. After immunization of mice, we
      evaluated the reduction in worm burden. We observed worm burden reductions of 17
      22%, 22%, 31-32% and 24-32% in animals immunized with the pUMVC3/Sm29,
      pUMVC3/SmTSP-2, pUMVC3/Chimera and pUMVC3/Sm29 + pUMVC3/SmTSP-2 plasmids,
      respectively. We evaluated the humoral response elicited by DNA vaccines, and
      animals immunized with pUMVC3/Sm29 and pUMVC3/Sm29 + pUMVC3/SmTSP-2 showed higher
      titers of anti-Sm29 antibodies. The cytokine profile produced by the spleen cells
      of immunized mice was then evaluated. We observed higher production of Th1
      cytokines, such as TNF-alpha and IFN-gamma, in vaccinated mice and no significant
      production of IL-4 and IL-5. The DNA vaccines tested in this study showed the
      ability to generate a protective immune response against schistosomiasis,
      probably through the production of Th1 cytokines. However, future strategies
      aiming to optimize the protective response induced by a chimeric DNA construct
      need to be developed. 

PMID- 25942638
TI  - A New MEMS Gyroscope Used for Single-Channel Damping.
AB  - The silicon micromechanical gyroscope, which will be introduced in this paper,
      represents a novel MEMS gyroscope concept. It is used for the damping of a single
      channel control system of rotating aircraft. It differs from common MEMS
      gyroscopes in that does not have a drive structure, itself, and only has a sense
      structure. It is installed on a rotating aircraft, and utilizes the aircraft spin
      to make its sensing element obtain angular momentum. When the aircraft is
      subjected to an angular rotation, a periodic Coriolis force is induced in the
      direction orthogonal to both the angular momentum and the angular velocity input
      axis. This novel MEMS gyroscope can thus sense angular velocity inputs. The
      output sensing signal is exactly an amplitude-modulation signal. Its envelope is
      proportional to the input angular velocity, and the carrier frequency corresponds
      to the spin frequency of the rotating aircraft, so the MEMS gyroscope can not
      only sense the transverse angular rotation of an aircraft, but also automatically
      change the carrier frequency over the change of spin frequency, making it very
      suitable for the damping of a single-channel control system of a rotating
      aircraft. In this paper, the motion equation of the MEMS gyroscope has been
      derived. Then, an analysis has been carried to solve the motion equation and
      dynamic parameters. Finally, an experimental validation has been done based on a
      precision three axis rate table. The correlation coefficients between the tested
      data and the theoretical values are 0.9969, 0.9872 and 0.9842, respectively.
      These results demonstrate that both the design and sensing mechanism are correct.

PMID- 25942637
TI  - Structure and assembly of group B streptococcus pilus 2b backbone protein.
AB  - Group B Streptococcus (GBS) is a major cause of invasive disease in infants. Like
      other Gram-positive bacteria, GBS uses a sortase C-catalyzed transpeptidation
      mechanism to generate cell surface pili from backbone and ancillary pilin
      precursor substrates. The three pilus types identified in GBS contain structural
      subunits that are highly immunogenic and are promising candidates for the
      development of a broadly-protective vaccine. Here we report the X-ray crystal
      structure of the backbone protein of pilus 2b (BP-2b) at 1.06A resolution. The
      structure reveals a classical IgG-like fold typical of the pilin subunits of
      other Gram-positive bacteria. The crystallized portion of the protein (residues
      185-468) encompasses domains D2 and D3 that together confer high stability to the
      protein due to the presence of an internal isopeptide bond within each domain.
      The D2+D3 region, lacking the N-terminal D1 domain, was as potent as the entire
      protein in conferring protection against GBS challenge in a well-established
      mouse model. By site-directed mutagenesis and complementation studies in GBS
      knock-out strains we identified the residues and motives essential for assembly
      of the BP-2b monomers into high-molecular weight complexes, thus providing new
      insights into pilus 2b polymerization. 

PMID- 25942639
TI  - Infrared thermal imaging system on a mobile phone.
AB  - A novel concept towards pervasively available low-cost infrared thermal imaging
      system lunched on a mobile phone (MTIS) was proposed and demonstrated in this
      article. Through digestion on the evolutional development of milestone
      technologies in the area, it can be found that the portable and low-cost design
      would become the main stream of thermal imager for civilian purposes. As a
      representative trial towards this important goal, a MTIS consisting of a thermal
      infrared module (TIM) and mobile phone with embedded exclusive software (IRAPP)
      was presented. The basic strategy for the TIM construction is illustrated,
      including sensor adoption and optical specification. The user-oriented software
      was developed in the Android environment by considering its popularity and
      expandability. Computational algorithms with non-uniformity correction and scene
      change detection are established to optimize the imaging quality and efficiency
      of TIM. The performance experiments and analysis indicated that the currently
      available detective distance for the MTIS is about 29 m. Furthermore, some family
      targeted utilization enabled by MTIS was also outlined, such as sudden infant
      death syndrome (SIDS) prevention, etc. This work suggests a ubiquitous way of
      significantly extending thermal infrared image into rather wide areas especially
      health care in the coming time. 

PMID- 25942640
TI  - Metal oxide gas sensor drift compensation using a two-dimensional classifier
      ensemble.
AB  - Sensor drift is the most challenging problem in gas sensing at present. We
      propose a novel two-dimensional classifier ensemble strategy to solve the gas
      discrimination problem, regardless of the gas concentration, with high accuracy
      over extended periods of time. This strategy is appropriate for multi-class
      classifiers that consist of combinations of pairwise classifiers, such as support
      vector machines. We compare the performance of the strategy with those of
      competing methods in an experiment based on a public dataset that was compiled
      over a period of three years. The experimental results demonstrate that the two
      dimensional ensemble outperforms the other methods considered. Furthermore, we
      propose a pre-aging process inspired by that applied to the sensors to improve
      the stability of the classifier ensemble. The experimental results demonstrate
      that the weight of each multi-class classifier model in the ensemble remains
      fairly static before and after the addition of new classifier models to the
      ensemble, when a pre-aging procedure is applied. 

PMID- 25942641
TI  - Mobile Robot Positioning with 433-MHz Wireless Motes with Varying Transmission
      Powers and a Particle Filter.
AB  - In wireless positioning systems, the transmitter's power is usually fixed. In
      this paper, we explore the use of varying transmission powers to increase the
      performance of a wireless localization system. To this extent, we have designed a
      robot positioning system based on wireless motes. Our motes use an inexpensive,
      low-power sub-1-GHz system-on-chip (CC1110) working in the 433-MHz ISM band. Our
      localization algorithm is based on a particle filter and infers the robot
      position by: (1) comparing the power received with the expected one; and (2)
      integrating the robot displacement. We demonstrate that the use of transmitters
      that vary their transmission power over time improves the performance of the
      wireless positioning system significantly, with respect to a system that uses
      fixed power transmitters. This opens the door for applications where the robot
      can localize itself actively by requesting the transmitters to change their power
      in real time. 

PMID- 25942642
TI  - A data acquisition protocol for a reactive wireless sensor network monitoring
      application.
AB  - Limiting energy consumption is one of the primary aims for most real-world
      deployments of wireless sensor networks. Unfortunately, attempts to optimize
      energy efficiency are often in conflict with the demand for network reactiveness
      to transmit urgent messages. In this article, we propose SWIFTNET: a reactive
      data acquisition scheme. It is built on the synergies arising from a combination
      of the data reduction methods and energy-efficient data compression schemes.
      Particularly, it combines compressed sensing, data prediction and adaptive
      sampling strategies. We show how this approach dramatically reduces the amount of
      unnecessary data transmission in the deployment for environmental monitoring and
      surveillance networks. SWIFTNET targets any monitoring applications that require
      high reactiveness with aggressive data collection and transmission. To test the
      performance of this method, we present a real-world testbed for a wildfire
      monitoring as a use-case. The results from our in-house deployment testbed of 15
      nodes have proven to be favorable. On average, over 50% communication reduction
      when compared with a default adaptive prediction method is achieved without any
      loss in accuracy. In addition, SWIFTNET is able to guarantee reactiveness by
      adjusting the sampling interval from 5 min up to 15 s in our application domain. 

PMID- 25942643
TI  - A new surface plasmon resonance immunosensor for triazine pesticide determination
      in bovine milk: a comparison with conventional amperometric and screen-printed
      immunodevices.
AB  - A detailed comparison was made of the analytical features of a new Surface
      Plasmon Resonance (SPR) immunodevice for triazine pesticide determination with
      those of two other amperometric (conventional and screen-printed) immunosensors
      and the advantages and disadvantages of the SPR method were thoroughly
      investigated. For conventional amperometric and screen-printed devices,
      "competitive" assays were used; conversely, the SPR transduction technique
      allowed a "direct" measurement format to be used. As far as the main analytical
      data are concerned, the SPR method does not seem to offer substantial advantages.
      Nevertheless the measurement time is much shorter and the measurement itself much
      easier to perform. Lastly several applications and recovery tests were carried
      out on bovine milk samples, before and after spiking, to check for triazine
      pesticides in the samples, obtaining satisfactory results. 

PMID- 25942644
TI  - Fluorescence spectroscopy and chemometric modeling for bioprocess monitoring.
AB  - On-line sensors for the detection of crucial process parameters are desirable for
      the monitoring, control and automation of processes in the biotechnology, food
      and pharma industry. Fluorescence spectroscopy as a highly developed and non
      invasive technique that enables the on-line measurements of substrate and product
      concentrations or the identification of characteristic process states. During a
      cultivation process significant changes occur in the fluorescence spectra. By
      means of chemometric modeling, prediction models can be calculated and applied
      for process supervision and control to provide increased quality and the
      productivity of bioprocesses. A range of applications for different
      microorganisms and analytes has been proposed during the last years. This
      contribution provides an overview of different analysis methods for the measured
      fluorescence spectra and the model-building chemometric methods used for various
      microbial cultivations. Most of these processes are observed using the BioView(r)
      Sensor, thanks to its robustness and insensitivity to adverse process conditions.
      Beyond that, the PLS-method is the most frequently used chemometric method for
      the calculation of process models and prediction of process variables. 

PMID- 25942645
TI  - Characterization of LEF1 High Expression and Novel Mutations in Adult Acute
      Lymphoblastic Leukemia.
AB  - Aberrant activation of the Wnt pathway plays a pathogenetic role in tumors and
      has been associated with adverse outcome in acute lymphoblastic leukemia (ALL).
      Lymphoid enhancer binding factor 1 (LEF1), a key mediator of Wnt signaling, has
      been linked to leukemic transformation, and LEF1 mutations have been identified
      in T-ALL. Here we found LEF1 is highly expressed in 25.0% adult ALL patients and
      LEF1 high expression was associated with high-risk leukemia factors (high WBC,
      Philadelphia chromosome positive, complex karyotype), shorter event-free survival
      (EFS), and high relapse rates in patients with B-ALL. LEF1 high expression is
      also associated with high mutation rate of Notch1 and JAK1 in T-ALL. We
      identified 2 novel LEF1 mutations (K86E and P106L) in 4 of 131 patients with ALL,
      and those patients with high-risk ALL (high WBC, complex karyotype). These
      results suggest a role for LEF1 mutations in leukemogenesis. We further explored
      the effect of the mutations on cell proliferation and found both mutations
      significantly promoted the proliferation of ALL cells. We also observed the
      effect of LEF1 and its mutations on the transcription of its targets, c-MYC and
      Cyclin D1. We found LEF1 increased the promoter activity of its targets c-MYC and
      Cyclin D1, and LEF1 K86E and P106L mutants further significantly enhanced this
      effect. We also observed that the c-MYC and Cyclin D1 mRNA levels were
      significantly increased in patients with LEF1 high expression compared with those
      with low expression. Taken together, our findings indicate high LEF1 expression
      and mutation are associated with high-risk leukemia and our results also revealed
      that LEF1 high expression and/or gain-of-function mutations are involved in
      leukemogenesis of ALL. 

PMID- 25942646
TI  - Intensive weekend group treatment for panic disorder and its impact on co
      occurring PTSD: A pilot study.
AB  - This pilot study examines the feasibility, acceptability, and potential
      effectiveness of delivering an intensive weekend group treatment for panic
      disorder (PD) to Veterans returning from deployments to Iraq and Afghanistan with
      co-occurring posttraumatic stress disorder (PTSD). The treatment program lasted
      6h each day and was delivered by two experienced therapists. Patients received
      core components of panic treatment, including psychoeducation, cognitive
      restructuring, and interoceptive exposure. The interoceptive exposure exercises
      directly targeted anxiety sensitivity, a psychological construct also implicated
      in the maintenance of PTSD. Eighty-nine percent of patients who expressed
      interest in the treatment attended a baseline evaluation, and 63% of those who
      were study eligible initiated treatment. Treatment retention was high, with all
      10 patients who initiated treatment completing the program. Veterans reported
      finding the treatment and delivery format highly acceptable and reported high
      levels of satisfaction. Panic symptoms improved significantly following the
      treatment and were maintained at a 7-month follow-up, with 71.4% of the sample
      reporting being panic free. Co-occurring PTSD symptoms also improved along with
      symptoms of anxiety and depression. Preliminary findings suggest that brief and
      intensive group treatments for PD/PTSD are a promising method of delivering
      cognitive behavioral therapy that may rapidly improve symptoms. This innovative
      treatment delivery format also may be a cost-effective way of increasing
      treatment engagement through increased access to quality care. 

PMID- 25942648
TI  - Gap analysis of pharmacokinetics and pharmacodynamics in burn patients: a review.
AB  - Severe burn injury results in a multifaceted physiological response that
      significantly alters drug pharmacokinetics and pharmacodynamics (PK/PD). This
      response includes hypovolemia, increased vascular permeability, increased
      interstitial hydrostatic pressure, vasodilation, and hypermetabolism. These
      physiologic alterations impact drug distribution and excretion-thus varying the
      drug therapeutic effect on the body or microorganism. To this end, in order to
      optimize critical care for the burn population it is essential to understand how
      burn injury alters PK/PD parameters. The purpose of this article is to describe
      the relationship between burn injury and drug PK/PD. We conducted a literature
      review via PubMed and Google to identify burn-related PK/PD studies. Search
      parameters included "pharmacokinetics," "pharmacodynamics," and "burns." Based on
      our search parameters, we located 38 articles that studied PK/PD parameters
      specifically in burns. Twenty-seven articles investigated PK/PD of antibiotics,
      10 assessed analgesics and sedatives, and one article researched an antacid. Out
      of the 37 articles, there were 19 different software programs used and eight
      different control groups. The mechanisms behind alterations in PK/PD in burns
      remain poorly understood. Dosing techniques must be adapted based on burn injury
      related changes in PK/PD parameters in order to ensure drug efficacy. Although
      several PK/PD studies have been undertaken in the burn population, there is wide
      variation in the analytical techniques, software, and study sample sizes used. In
      order to refine dosing techniques in burns and consequently improve patient
      outcomes, there must be harmonization among PK/PD analyses. 

PMID- 25942649
TI  - Estimating the national cost burden from burns resulting from methamphetamine
      manufacturing.

PMID- 25942647
TI  - Crossroads of PI3K and Rac pathways.
AB  - Rac and PI3Ks are intracellular signal transducers able to regulate multiple
      signaling pathways fundamental for cell behavior. PI3Ks are lipid kinases that
      produce phosphorylated lipids which, in turn, transduce extracellular cues within
      the cell, while Rac is a small G protein that impacts on actin organization.
      Compelling evidence indicates that in multiple circumstances the 2 signaling
      pathways appear intermingled. For instance, phosphorylated lipids produced by
      PI3Ks recruit and activate GEF and GAP proteins, key modulators of Rac function.
      Conversely, PI3Ks interact with activated Rac, leading to Rac signaling
      amplification. This review summarizes the molecular mechanisms underlying the
      cross-talk between Rac and PI3K signaling in 2 different processes, cell
      migration and ROS production. 

PMID- 25942651
TI  - Richard Dadd: the patient, the artist, and the "face of madness".
AB  - Richard Dadd (1817-1886) was a well-known Victorian artist who murdered his
      father, compelled by the delusion that a demonic force possessed his father's
      body. He was one of the first to bypass execution by reason of insanity and spent
      the remainder of his life in the Bethlem and Broadmoor asylums. Dadd is rare both
      as a patient and an artist because he left behind nearly a 40-year record of
      artwork and journals, which constitute a unique medical and psychiatric resource
      at a time when the ideas on the relationship of facial expression and madness
      were changing. Sir Charles Bell's (1774-1842) widely accepted views that the
      "face of madness" is bestial and anatomically distinctive were being challenged
      by such physicians as Sir Alexander Morison (1779-1866), who was also Dadd's own
      "alienist" (i.e., psychiatrist). The purpose of this article is to explore the
      nature and extent of the influence of Bell and Morison on Dadd, which has not
      been brought out in the existing studies. By a comparative analysis, it will be
      shown that Dadd may have conveyed a different view in his works that foreshadows
      subsequent developments that are closer to a modern understanding. 

PMID- 25942650
TI  - SK channels and calmodulin.
AB  - Calcium ions are Nature's most widely used signaling mechanism, mediating
      communication between pathways at virtually every physiological level. Ion
      channels are no exception, as the activities of a wide range of ion channels are
      intricately shaped by fluctuations in intracellular Ca(2+) levels. Mirroring the
      importance and the breadth of Ca(2+) signaling, free Ca(2+) levels are tightly
      controlled, and a myriad of Ca(2+) binding proteins transduce Ca(2+) signals,
      each with its own nuance, comprising a constantly changing symphony of metabolic
      activity. The founding member of Ca(2+) binding proteins is calmodulin (CaM), a
      small, acidic, modular protein endowed with gymnastic-like flexibility and E-F
      hand motifs that chelate Ca(2+) ions. In this review, I will trace the history
      that led to the realization that CaM serves as the Ca(2+)-gating cue for SK
      channels, the experiments that revealed that CaM is an intrinsic subunit of SK
      channels, and itself a target of regulation. 

PMID- 25942652
TI  - Cardiovascular Safety of Plant Sterol and Stanol Consumption.
AB  - Plant sterols and stanols as components of functional foods are widely used for
      cholesterol lowering. The regular intake of these functional foods is associated
      with a decrease in low density lipoprotein cholesterol of about 10 % and an
      increase in plasma plant sterol or stanol concentrations by about a factor of 2.
      There is no doubt that a decrease in low density lipoprotein cholesterol is
      beneficial to cardiovascular health. However, due to the concomitant increase in
      circulating plant sterols safety issues associated with the intake of plant
      sterol containing functional foods have been raised. Herein, we will review and
      evaluate those arguments raised against the use of plant sterols and stanols. 

PMID- 25942655
TI  - Is altered dopamine turnover the missing link between insulin resistance and
      cognitive decline?

PMID- 25942653
TI  - Disorders of sex development: effect of molecular diagnostics.
AB  - Disorders of sex development (DSDs) are a diverse group of conditions that can be
      challenging to diagnose accurately using standard phenotypic and biochemical
      approaches. Obtaining a specific diagnosis can be important for identifying
      potentially life-threatening associated disorders, as well as providing
      information to guide parents in deciding on the most appropriate management for
      their child. Within the past 5 years, advances in molecular methodologies have
      helped to identify several novel causes of DSDs; molecular tests to aid diagnosis
      and genetic counselling have now been adopted into clinical practice.
      Occasionally, genetic profiling of embryos prior to implantation as an adjunct to
      assisted reproduction, prenatal diagnosis of at-risk pregnancies and confirmatory
      testing of positive results found during newborn biochemical screening are
      performed. Of the available genetic tests, the candidate gene approach is the
      most popular. New high-throughput DNA analysis could enable a genetic diagnosis
      to be made when the aetiology is unknown or many differential diagnoses are
      possible. Nonetheless, concerns exist about the use of genetic tests. For
      instance, a diagnosis is not always possible even using new molecular approaches
      (which can be worrying for the parents) and incidental information obtained
      during the test might cause anxiety. Careful selection of the genetic test
      indicated for each condition remains important for good clinical practice. The
      purpose of this Review is to describe advances in molecular biological techniques
      for diagnosing DSDs. 

PMID- 25942656
TI  - Therapy: SGLT2 inhibitor dapagliflozin promotes glucagon secretion in alpha islet
      cells.

PMID- 25942654
TI  - Genetics of androgen metabolism in women with infertility and hypoandrogenism.
AB  - Hypoandrogenism in women with low functional ovarian reserve (LFOR, defined as an
      abnormally low number of small growing follicles) adversely affects fertility.
      The androgen precursor dehydroepiandrosterone (DHEA) is increasingly used to
      supplement treatment protocols in women with LFOR undergoing in vitro
      fertilization. Due to differences in androgen metabolism, however, responses to
      DHEA supplementation vary between patients. In addition to overall declines in
      steroidogenic capacity with advancing age, genetic factors, which result in
      altered expression or enzymatic function of key steroidogenic proteins or their
      upstream regulators, might further exacerbate variations in the conversion of
      DHEA to testosterone. In this Review, we discuss in vitro studies and animal
      models of polymorphisms and gene mutations that affect the conversion of DHEA to
      testosterone and attempt to elucidate how these variations affect female hormone
      profiles. We also discuss treatment options that modulate levels of testosterone
      by targeting the expression of steroidogenic genes. Common variants in genes
      encoding DHEA sulphotransferase, aromatase, steroid 5alpha-reductase, androgen
      receptor, sex-hormone binding globulin, fragile X mental retardation protein and
      breast cancer type 1 susceptibility protein have been implicated in androgen
      metabolism and, therefore, can affect levels of androgens in women. Short of
      screening for all potential genetic variants, hormonal assessments of patients
      with low testosterone levels after DHEA supplementation facilitate identification
      of underlying genetic defects. The genetic predisposition of patients can then be
      used to design individualized fertility treatments. 

PMID- 25942658
TI  - Infantile hemangiomas.

PMID- 25942659
TI  - Anesthetic blister induction to identify biopsy site prior to Mohs surgery.
AB  - BACKGROUND: Wrong-site surgery in dermatology often occurs due to difficulty
      finding the initial biopsy site prior to Mohs surgery. Patients frequently
      present for Mohs surgery weeks to months following the initial biopsy site.
      Visualization of the biopsy site may become difficult at presentation due to
      healing. <br/> OBJECTIVE: To investigate the utility of anesthetic blister
      induction at a suspected biopsy site to identify the location prior to Mohs
      surgery. The proposed technique is visualization of a blister that is induced by
      local anesthetic administration at the proposed biopsy site. The addition of this
      technique among others such as curettage, dermoscopy, and UV fluorescence can
      prevent wrong-site surgery. <br/> METHODS: A biopsy site of a squamous cell
      carcinoma on a patient was compared via photography for visibility at the time of
      initial biopsy, weeks following biopsy, and post-anesthetic blister induction.
      <BR/> RESULTS: The biopsy site was easier to locate with the assistance of a
      blister that formed as a result of local anesthetic administration. <br/>
      CONCLUSION: Blister induction by local anesthetic administration can assist in
      accurately identifying healed or obscured biopsy sites.

PMID- 25942660
TI  - Leprosy masquerading as rheumatoid arthritis.

PMID- 25942657
TI  - Thyroid hormone transporters--functions and clinical implications.
AB  - The cellular influx and efflux of thyroid hormones are facilitated by
      transmembrane protein transporters. Of these transporters, monocarboxylate
      transporter 8 (MCT8) is the only one specific for the transport of thyroid
      hormones and some of their derivatives. Mutations in SLC16A2, the gene that
      encodes MCT8, lead to an X-linked syndrome with severe neurological impairment
      and altered concentrations of thyroid hormones. Histopathological analysis of
      brain tissue from patients who have impaired MCT8 function indicates that brain
      lesions start prenatally, and are most probably the result of cerebral
      hypothyroidism. A Slc16a2 knockout mouse model has revealed that Mct8 is an
      important mediator of thyroid hormone transport, especially T3, through the blood
      brain barrier. However, unlike humans with an MCT8 deficiency, these mice do not
      have neurological impairment. One explanation for this discrepancy could be
      differences in expression of the T4 transporter OATP1C1 in the blood-brain
      barrier; OATP1C1 is more abundant in rodents than in primates and permits the
      passage of T4 in the absence of T3 transport, thus preventing full cerebral
      hypothyroidism. In this Review, we discuss the relevance of thyroid hormone
      transporters in health and disease, with a particular focus on the
      pathophysiology of MCT8 mutations. 

PMID- 25942661
TI  - Before or after: is there a connection between the use of adjunctive nonmelanoma
      skin cancer treatments and subsequent invasive tumors?
AB  - Although the therapeutic gold standard for basal cell carcinomas (BCCs) is
      surgical excision, imiquimod, fluorouracil cream, and photodynamic therapy are
      frequently used. All 3 modalities have been shown to be efficacious for the
      treatment of superficial BCCs as well as other nonmelanoma skin cancers; however,
      recent reports have emerged implicating these agents in causing more aggressive
      recurrent subtypes of BCCs. Here we review this literature as well as offer an
      alternative explanation for these tumors. 

PMID- 25942662
TI  - Characterization and assessment of nanoencapsulated sanguinarine chloride as a
      potential treatment for melanoma.
AB  - Sanguinarine has a history of use in both folk medicine and early dermatology for
      the treatment of cutaneous neoplasms. Applied indiscriminately, bloodroot is an
      escharotic agent with potential to cause extensive tissue necrosis. However, when
      used in a controlled fashion, sanguinarine imparts selective cytotoxic/anti
      proliferative activity through multiple mechanisms against human/ murine
      melanoma. To exploit sanguinarine's observed activity against melanoma, a
      targeted delivery system is required. We present a sol-gel based nanoparticulate
      platform for encapsulating sanguinarine chloride(sang-np)-a targeted therapeutic
      capable of steady, reliable delivery of predictable quantities of drug over a
      sustained time period with minimal undesirable effects. Size and release kinetics
      of sang-np were characterized using dynamic light scattering and ultraviolet
      visible spectroscopy respectively. In vitro efficacy of sang-np was assessed. At
      both 2 and 24 hours, free sanguinarine killed > 90% of B16 melanoma cells,
      assessed via MTT assay. At 2 hours, sang-np killed a portion of melanoma cells,
      increasing to percentages comparable to free sanguinarine by 24 hours.
      Control(empty) nanoparticles exerted minimal toxicity to melanoma cells at both
      time points. TUNEL assay revealed that treatment with both sanguinarine and sang
      np induces apoptosis in B16 melanoma cells, suggesting that both treatments act
      via the same mechanism of action. These data confirm controlled release of
      sanguinarine from sang-np, as well as comparable efficacy and mechanism of action
      to sanguinarine alone. This suggests that nanoparticle delivery of sanguinarine
      may be a unique approach to capitalize on this potent agent's inherent anti-tumor
      activity and overcome many of the limitations with its current formulation.

PMID- 25942663
TI  - The role of the cutaneous microbiome in skin cancer: lessons learned from the
      gut.
AB  - The human microbiome has recently gained prominence as a major factor in health
      and disease. Here we review the literature regarding the microbiome and cancer
      and suggest how the microbiome may be manipulated for improved health outcomes.
      The gut microbiome has been relatively well studied, and the mechanisms of how it
      may increase or decrease the risk of certain cancers may apply to the skin
      microbiome. Additionally, the gut microbiome may directly impact the risk of
      cancer in the skin and other organs by promoting systemic inflammation. The skin
      microbiome itself is as diverse as the gut microbiome, but research has just
      begun to unravel its influence on the host. Like the gut microbiome, it affects
      the risk for several diseases, including cancer. By using healthpromoting strains
      from the microbiome in oral or topical probiotics, it may be possible to reduce
      the risk of skin cancer and perhaps even increase the likelihood of successful
      treatment.

PMID- 25942664
TI  - Safe and efficacious use of intralesional steroids for the treatment of focally
      resistant mycosis fungoides.
AB  - Cutaneous T-cell lymphoma is a cancer of skin-homing T cells, of which mycosis
      fungoides (MF) is the most common variant. MF treatments range from topical
      steroids to systemic chemotherapy. Resistant cutaneous MF nodules can present a
      special challenge in that typical topical therapies may not penetrate thick
      lesions, and increasing systemic therapy brings added risk of side effects. We
      report successful use of intralesional steroids (ILS) for treatment-resistant MF,
      including tumor-stage plaques and nodules in 4 consecutive patients with focally
      resistant MF. ILS have been widely used to treat a broad range of cutaneous
      conditions such as alopecia areata and keloids. Side effects of ILS include
      hypopigmentation, atrophy, telangiectasias, lilac discoloration, acne, and
      striae. Rarely, and in circumstances involving unusually large doses, ILS may
      cause Cushing's syndrome, hypothalamus-pituitary-adrenal axis suppression, and
      reduced bone mineral density. The MF patients tolerated treatment well without
      any of the above side effects other than local hypopigmention in a single
      patient. These results point toward further exploration into ILS as a treatment
      for focally resistant MF.

PMID- 25942665
TI  - Bimatoprost-induced chemical blepharoplasty.
AB  - We report significant changes in the appearance of the periorbital area, beyond
      eyelash enhancement, induced by the topical application of bimatoprost ophthalmic
      solution, 0.03% (Latisse(r), Allergan, Inc., Irvine, CA). To our knowledge, this
      is the first report in the dermatology or plastic surgery literature describing
      the rejuvenating effect and overall improvement in the appearance of the
      periorbital area resulting from applying Latisse to the upper eyelid margins. To
      date, reports in the literature discuss side-effects and potential complications
      of topical bimatoprost therapy causing a constellation of findings known as PAP
      (prostaglandin-associated periorbitopathy). While periorbitopathy implies
      pathology or a state of disease, we report changes that can be perceived as an
      improvement in the overall appearance of the periorbital area. We, therefore,
      propose a name change from PAP to PAPS - prostaglandin- associated <i>periorbital
      syndrome</i>. This better describes the beneficial, as well as the possible
      negative effects of topical bimatoprost. Although there is a risk for periorbital
      disfigurement, when used bilaterally, in properly selected candidates and
      titrated appropriately, bimatoprost can be beneficial. The striking improvement
      in the appearance of some individuals warrants further research into the
      potential use of topical bimatoprost to achieve a "chemical blepharoplasty."

PMID- 25942666
TI  - Steroid-Free Over-the-Counter Eczema Skin Care Formulations Reduce Risk of Flare,
      Prolong Time to Flare, and Reduce Eczema Symptoms in Pediatric Subjects With
      Atopic Dermatitis.
AB  - INTRODUCTION: Atopic dermatitis (AD) is a chronic skin condition associated with
      decreased barrier function resulting in periodic flare-ups of erythematous and
      pruritic lesions. Guidelines recommend daily treatment of atopic skin with
      emollient moisturizers for prevention of flares and maintenance of the flare-free
      state. This study evaluated the efficacy of 2 steroid-free, nonprescription
      eczema skin care formulations for reducing the risk of flare and relieving
      symptoms in infants and children with AD: Body Cream for the daily maintenance
      treatment of atopic skin and Flare Treatment for the treatment of atopic flares.
      METHODS: After a 2-week washout period, subjects (N=45; mean age 3.5 years) were
      randomized to cleanser plus daily moisturizing with Body Cream (moisturizer
      group) or cleanser only (control group) for 6 months or until flare. Subjects
      experiencing flare received Flare Treatment for 4 weeks. RESULTS: The incidence
      of flare was significantly lower in the moisturizer group compared with the
      control group (21% vs 65%; <em>P</em>=.006), while the median time to flare was
      shorter in the control group (28 vs >180 days). Risk of flare was reduced by
      44.1% after 6 months of Body Cream application. Flare Treatment reduced overall
      eczema symptom severity at week 2 and week 4; 78.9% of flares had improved or
      cleared at week 4. CONCLUSIONS: Body Cream reduced the incidence of flare and the
      time to flare, reinforcing guidelines that daily emollient therapy should be an
      integral part of the maintenance treatment plan for the prevention of disease
      flares. Body Cream and Flare Treatment are effective over-the-counter steroid
      free options for management of AD in children.

PMID- 25942667
TI  - Cosmetic complications: rare and serious events following botulinum toxin and
      soft tissue filler administration.
AB  - BACKGROUND: Botulinum toxin (BTX) and soft tissue fillers continue to gain in
      popularity due to their safety, affordability, quick effects, and short recovery
      times. With the excellent safety profile of BTX and soft tissue fillers, patients
      may develop a nonchalant attitude towards treatment with injectables. However, it
      is important for both patient and physician to be familiar with all the possible
      complications, both common and uncommon. OBJECTIVE: This article aims to review
      the rare but serious complications associated with the injectables used in
      cosmetic dermatology, and the pathogenesis, diagnosis, and management of each.
      METHODS AND MATERIALS: A literature review for case reports pertaining to rare
      adverse events following botulinum toxin or soft tissue fillers was performed
      using the MEDLINE database. RESULTS: Complications of BTX included dry eye
      syndrome, strabismus and diplopia, superficial temporal artery pseudoaneurysm,
      neck weakness, hoarseness, and dysphagia. Complications associated with soft
      tissue fillers included tissue necrosis, inflammatory nodules, hypersensitivity
      reaction, and blindness and cerebral ischemia. CONCLUSION: The injector should be
      comfortable in diagnosing and managing the above complications, and the patient
      should be counseled about these potentially harmful adverse events prior to
      injection.

PMID- 25942668
TI  - Management of onychomycosis and co-existing tinea pedis.
AB  - Onychomycosis is a common nail infection that often co-exists with tinea pedis.
      Surveys have suggested the diseases co-exist in at least one third of patients,
      although actual numbers may be a lot higher due to significant under-reporting.
      The importance of evaluating and treating both diseases is being increasingly
      recognized, however, data on improved outcomes, and the potential to minimize re
      infection are limited. We review a recent post hoc analysis of two large studies
      treating mild to moderate onychomycosis with efinaconazole topical solution, 10%,
      demonstrating that complete cure rates of onychomycosis are significantly
      improved when any co-existing tinea pedis is also treated.

PMID- 25942669
TI  - Five-Year Trend in the Number of Dermatologic Clinical Drug Trials Registered on
      ClinicalTrials.gov.
AB  - BACKGROUND: There is a reported global decrease in the number of clinical trials
      conducted in recent years. We aimed to determine if this declining trend can be
      extrapolated to dermatologic clinical trials. METHODS: We conducted a query of
      ClinicalTrials.gov for dermatologic clinical trials from 2009 to 2013 for 6
      common skin conditions: acne, psoriasis, rosacea, eczema and atopic dermatitis,
      actinic keratosis, and skin cancer. Results were sorted by condition and number
      of study subjects. This study did not involve any participants apart from the
      researchers. RESULTS: Although there is an increasing trend in the number of
      trials performed annually, the results were not significant (P =.08). The average
      number of patients per study has not significantly changed (P =.12), but there
      was a significant increase in the number of large studies (201+ subjects)
      conducted over time (P =.002). Although there was significant variation based on
      dermatologic condition studied (global statistic P=.01), only skin cancer
      demonstrated a significant change in the number of studies registered annually
      (beta=10.6 studies/year, P =.04). CONCLUSIONS AND RELEVANCE: The sky does not
      appear to be falling, at least not yet, with regard to continued development of
      treatments for patients with skin disease.

PMID- 25942670
TI  - A case of multiple atypical nevi with co-localized Basal cell carcinomas on the
      scalp: insight into the pathogenesis.
AB  - The authors report a case of a 29-year-old female with multiple lesions on the
      scalp containing an atypical nevus and a co-localized basal cell carcinoma (BCC)
      in the same specimen. This is the first description of such a case in the
      literature. The peculiar co-existence of these 2 neoplasms in the same specimen
      in multiple skin lesions raises the possibility of an unknown mutation(s) that
      increases the risk of developing both conditions; and this case illustrates that
      the signaling pathways mediating the development of atypical nevi may interact
      with those associated with BCCs. Additionally, crosstalk between melanocytes and
      basal keratinocytes, which are both located in the basal layer of the epidermis,
      may contribute to the development of these coexisting neoplasms.

PMID- 25942671
TI  - Cutaneous manifestations of vemurafenib therapy for metastatic melanoma.
AB  - Vemurafenib, a BRAF inhibitor, is FDA-approved for the treatment of metastatic
      melanoma in patients who harbor the BRAF V600E mutation. By inhibiting BRAF,
      vemurafenib prevents the mitogen-activated protein kinase (MAPK) pathway from
      driving melanoma growth. Here we present a patient with paradoxical activation of
      the MAPK pathway by vemurafenib, ultimately resulting in deleterious cutaneous
      manifestations. An emphasis on close follow-up is warranted for new or changing
      lesions for patients on this medication and other BRAF inhibitors.

PMID- 25942672
TI  - Primary Cutaneous T-cell Lymphoma With Aberrant CD-20 Expression.
AB  - IMPORTANCE: Primary cutaneous T-cell lymphoma with aberrant expression of cluster
      of differentiation (CD) 20 is an exceedingly rare manifestation of cutaneous T
      cell lymphoma that is easily misdiagnosed as B-cell lymphoma. The significance
      and prognostic implications of T-cell neoplasms demonstrating the classic CD20 B
      cell marker have yet to be elucidated. OBSERVATIONS: We present a case of primary
      cutaneous T-cell lymphoma with aberrant CD20 expression in a 97-year-old male who
      presented with a 2-year history of pruritic plaques and nodules covering his
      body. Nodule biopsy demonstrated a dense, atypical dermal T-lymphocytic
      infiltrate consisting of predominantly large cells exhibiting classic T-cell
      markers (CD4 and CD3) along with aberrant expression of the B-cell marker CD20
      (expressed in late pro-B to mature B cells). CONCLUSIONS: The patient was
      tentatively diagnosed with primary cutaneous CD30-negative large T-cell lymphoma
      with aberrant CD20 co-expression, pending workup to exclude systemic lymphoma
      with cutaneous involvement. He unfortunately passed away 4 days after the initial
      dermatologic presentation. RELEVANCE: The prognostic implications of CD20
      positive T-cell lymphoma require further exploration, along with the potential
      role of CD20 antibody in treatment of this rare malignancy.

PMID- 25942673
TI  - Resident Rounds Part III: Case Report: Fatal Cryptococcal Panniculitis in a Lung
      Transplant Recipient.
AB  - Cryptococcal panniculitis is a rare entity previously reported in only 13 solid
      organ transplant (SOT) recipients. Cutaneous cryptococcosis in SOT recipients
      warrants extensive systemic workup and treatment as if central nervous system
      (CNS) disease is present. It should be included in the differential diagnosis of
      panniculitis in the immunocompromised host, as early diagnosis and treatment are
      critical. We report a fatal case of cryptococcal panniculitis in a 44-year-old
      lung transplant recipient. 

PMID- 25942674
TI  - Report of a case of a dermatophytoma successfully treated with topical
      efinaconazole 10% solution.
AB  - Onychomycosis is a common fungal infection of the nail unit that results in
      discoloration, subungual debris, thickening, onycholysis, and often pain and
      impairment of mobility. Dermatophytomas are characterized by a thick fungal mass
      within and under the nail plate and are especially resistant to treatment. Here
      we report a case of a patient with a dermatophytoma who had failed oral
      terbinafine but was successfully treated with efinaconazole 10% topical solution.

PMID- 25942675
TI  - Electrophysiologic identification and monitoring of the external branch of
      superior laryngeal nerve during thyroidectomy.
AB  - OBJECTIVE: The aim of the study is to examine the correlation between weight,
      gender, and race with external branch of superior laryngeal nerve (EBSLN)
      visualization. Furthermore, we compared normative EBSLN neural-monitoring values
      to those of the recurrent laryngeal nerve (RLN). STUDY DESIGN: Retrospective
      study. SETTING: North American tertiary academic hospital. SUBJECTS AND METHODS:
      A retrospective, institutional review board-approved review was carried out on
      patients undergoing thyroid surgery by a single surgeon over 3.5 years.
      Preoperative and postoperative laryngoscopy was done on all patients in
      accordance with recently published American Academy of Otolaryngology voice
      optimization at thyroidectomy guidelines, and patients' clinical and operative
      relevant data were collected. RESULTS: A total of 447 nerves were at risk in 371
      thyroidectomy patients. Of these nerves at risk, 237 (53.02%) were visualized and
      stimulated. The average amplitude and latency for the EBSLN were significantly
      lower when compared to the amplitude and the latency of RLN stimulation (P <
      0.0001, P < 0.0001, respectively). There was no gender or racial disparity. Out
      of our study population, the EBSLN was identified in 64.56% in nonobese patients,
      whereas it was only 40.00% in obese patients (P < 0.001). Additionally, of the 56
      patients in whom the EBSLN was visualized on one side and who further underwent
      bilateral neck exploration, 41 (73%) had visualization of the nerve on the
      contralateral side as well. CONCLUSION: EBSLN is less likely to be visualized in
      obese patients; however, there was no gender or racial disparity. Stimulation of
      EBSLN was felt to be a useful adjunct during superior pole dissection to assure
      the nerve integrity. LEVEL OF EVIDENCE: 4.

PMID- 25942677
TI  - Oxidative tryptophan modification by terpene- and squalene-hydroperoxides and a
      possible link to cross-reactions in diagnostic tests.
AB  - Hydroperoxides can act as specific haptens and oxidatively modify proteins.
      Terpene hydroperoxides trigger unusually high frequencies of positive skin
      reactions in human patients if tested at high concentrations. It is unknown
      whether this is due to specific hapten formation. Here, we show that both terpene
      hydroperoxides and the endogenous hydroperoxide formed from squalene can
      oxidatively modify tryptophan. Oxidative modifications of Trp were recently
      postulated to explain cross-sensitization between unrelated photosensitizers.
      Current observations may extend this hypothesis: Oxidative events triggered by
      endogenous hydroperoxides and hydroperoxides/oxidants derived from xenobiotics
      might lead to a sensitized state detected by patch tests with high concentrations
      of hydroperoxides.

PMID- 25942676
TI  - Overlapping Patterns of Rapid Evolution in the Nucleic Acid Sensors cGAS and OAS1
      Suggest a Common Mechanism of Pathogen Antagonism and Escape.
AB  - A diverse subset of pattern recognition receptors (PRRs) detects pathogen
      associated nucleic acids to initiate crucial innate immune responses in host
      organisms. Reflecting their importance for host defense, pathogens encode various
      countermeasures to evade or inhibit these immune effectors. PRRs directly engaged
      by pathogen inhibitors often evolve under recurrent bouts of positive selection
      that have been described as molecular 'arms races.' Cyclic GMP-AMP synthase
      (cGAS) was recently identified as a key PRR. Upon binding cytoplasmic double
      stranded DNA (dsDNA) from various viruses, cGAS generates the small nucleotide
      secondary messenger cGAMP to signal activation of innate defenses. Here we report
      an evolutionary history of cGAS with recurrent positive selection in the primate
      lineage. Recent studies indicate a high degree of structural similarity between
      cGAS and 2'-5'-oligoadenylate synthase 1 (OAS1), a PRR that detects double
      stranded RNA (dsRNA), despite low sequence identity between the respective genes.
      We present comprehensive comparative evolutionary analysis of cGAS and OAS1
      primate sequences and observe positive selection at nucleic acid binding
      interfaces and distributed throughout both genes. Our data revealed homologous
      regions with strong signatures of positive selection, suggesting common
      mechanisms employed by unknown pathogen encoded inhibitors and similar modes of
      evasion from antagonism. Our analysis of cGAS diversification also identified
      alternately spliced forms missing multiple sites under positive selection.
      Further analysis of selection on the OAS family in primates, which comprises
      OAS1, OAS2, OAS3 and OASL, suggests a hypothesis where gene duplications and
      domain fusion events result in paralogs that provide another means of escaping
      pathogen inhibitors. Together our comparative evolutionary analysis of cGAS and
      OAS provides new insights into distinct mechanisms by which key molecular
      sentinels of the innate immune system have adapted to circumvent viral-encoded
      inhibitors. 

PMID- 25942678
TI  - I2-Catalyzed Aerobic Oxidative C(sp(3))-H Amination/C-N Cleavage of Tertiary
      Amine: Synthesis of Quinazolines and Quinazolinones.
AB  - An iodine-catalyzed oxidative C(sp(3))-H amination/C-N cleavage of tertiary
      amines couducted under an oxygen atmosphere has been developed and affords a
      route to quinazolines and quinazolinones in good to excellent yields via a domino
      ring annulation. The method is metal-free, peroxide-free, and operationally
      simple to implement with a wide scope of substrates and represents a new avenue
      for multiple C-N bond formations. 

PMID- 25942679
TI  - Bioactivity and chemical characterisation of Lophostemon suaveolens--an endemic
      Australian Aboriginal traditional medicinal plant.
AB  - Lophostemon suaveolens is a relatively unexplored endemic medicinal plant of
      Australia. Extracts of fresh leaves of L. suaveolens obtained from sequential
      extraction with n-hexane and dichloromethane exhibited antibacterial activity in
      the disc diffusion and MTT microdilution assays against Streptococcus pyogenes
      and methicillin sensitive and resistant strains of Staphylococcus aureus (minimum
      bactericidal concentration < 63 MUg/mL). The dichloromethane extract and
      chromatographic fractions therein inhibited nitric oxide in RAW264.7 murine
      macrophages (IC50 3.7-11.6 MUg/mL) and also PGE2 in 3T3 murine fibroblasts (IC50
      2.8-19.7 MUg/mL). The crude n-hexane, dichloromethane and water extracts of the
      leaves and chromatographic fractions from the dichloromethane extract also showed
      modest antioxidant activity in the ORAC assay. GC-MS analysis of the n-hexane
      fraction showed the presence of the antibacterial compounds aromadendrene,
      spathulenol, beta-caryophyllene, alpha-humulene and alpha-pinene and the anti
      inflammatory compounds beta-caryophyllene and spathulenol. Fractionation of the
      dichloromethane extract led to the isolation of eucalyptin and the known anti
      inflammatory compound betulinic acid.

PMID- 25942680
TI  - Interfacial thermal transport and structural preferences in carbon nanotube
      polyamide-6,6 nanocomposites: how important are chemical functionalization
      effects?
AB  - We employ reverse nonequilibrium molecular dynamics simulations to investigate
      the interfacial heat transfer in composites formed by an ungrafted or a grafted
      carbon nanotube which is surrounded by oligomeric polyamide-6,6 chains. The
      structural properties of the polymer matrix and the grafted chains are also
      studied. The influence of the grafting density, the length of the grafted chains
      as well as their chemical composition on the interfacial thermal conductivity
      (lambdai) are in the focus of our computational study. For the considered grafted
      polyethylene and polyamide chains we do not find a sizeable difference in the
      observed lambdai values. In contrast to this insensitivity, we predict a rather
      strong influence on lambdai by the grafting density and the length of the grafted
      chains. This dependence is an outcome of modifications in the structural
      properties of the polymer matrix as well as the grafted chains. Functionalization
      of the nanotube has a sizeable influence on the interfacial thermal conductivity.
      Its enhancement is caused by the chemical bonds between the nanotube and grafted
      chain atoms which reduce the number of Kapitza resistances hindering the heat
      transfer in polymer samples. The phonon density of states profiles confined to
      the bonded nanotube and the grafted chain atoms are used to emphasize the phonon
      support of the thermal conductivity in nanocomposites with grafted tubes.
      Strategies to tailor nanotube containing composites with higher thermal
      conductivities than that realized in the bare polymer are shortly touched. 

PMID- 25942681
TI  - A Novel Technique of Vacuum-assisted Wound Closure That Functions as a Delayed
      Primary Closure.
AB  - Contaminated midline abdominal wounds are often left open and allowed to close
      via secondary intention to prevent surgical site infections. Negative pressure
      wound therapy (NPWT) devices have decreased time of healing by secondary
      intention when compared to the prior standard of moist dressings. The authors
      report a modification of NPWT that utilizes the unique characteristics of the
      negative pressure system to achieve delayed primary closure while preventing
      surgical site infections by continuously draining the wound effluent. 

PMID- 25942682
TI  -  Topical misoprostol and wound healing in rats.
AB  - Background. It is well known that prostaglandins play an integral part in wound
      healing, yet there is scant evidence to support the use of exogenous topical
      prostaglandins as potential wound healing agents. This study on rats begins that
      exploration by studying the effects of topical misoprostol on acute wound
      healing. METHODS: Twenty-six rats had 2-cm x 2-cm full-thickness wounds created
      on their dorsal surface: one-half had topical misoprostol powder mixed with
      saline applied daily for 3 weeks, while the other half had only normal saline
      applied. Photos to measure wound size were taken every 3 days to document any
      changes. RESULTS: Statistical analysis revealed that topical misoprostol can lead
      to decreased healing times. CONCLUSION: Topical misoprostol powder can decrease
      the healing time of acute wounds in rats. Further studies are needed to confirm
      this finding, as well as to explore its use in chronic wounds.

PMID- 25942683
TI  - Streamlining the management of patients with problematic wounds: must a
      multidisciplinary team formulate all patient management plans?
AB  - The importance of the management of patients with problem wounds by
      multidisciplinary teams (MDTs) is uniformly emphasized. The aim of this study was
      to examine the impact of the review of individual cases by MDT on the management
      plan proposed by the Surgical Wound Care Specialist (SWCS). METHODS: Trained
      "field" nurse specialists assessed problem wound patients in ambulatory care
      settings followed by the evaluation by the SWCS. The initial management plan
      (IMP), including a statement regarding the probability of the plan change by the
      MDT, was formulated by a SWCS based on evaluation of electronically transmitted
      patient record (including photographs) by a "field" nurse, followed by direct
      face-to-face evaluation by the same SWCS. Subsequently, the MDT reviewed
      individual cases formulating the final management plan (FMP). Over a 24-month
      period (2005-2006) the MDT reviewed clinical data for 124 new patients and a
      collective decision about the FMP was made. RESULTS: As the result of the MDT
      discussion, 3 of the 124 cases had clinical management changes (clinically
      important disagreement) and 5 trivial assessment changes. All cases were
      identified (among 4 others) by SWCS as potential "change cases" before the MDT
      meeting. CONCLUSION: The MDT review made no difference in the case management
      plan in 93.6%, with significant changes recommended only in 2.4% of cases. In
      consideration of a potential management plan change the SWCS correctly identified
      cases requiring discussion, which indicates that a selective rather than blanket
      approach would be effective. This has the potential to expedite patient care and
      to reduce costs without affecting patient care.

PMID- 25942684
TI  -   Mycobacterium abscessus Infection of a Puncture Wound of the Han.
AB  - The authors present a case report of a patient who suffered a puncture wound of
      the hand. The patient developed a chronic wound on the dorsum of her hand
      secondary to Mycobacterium abscessus. Debridement of the wound was performed and
      operative cultures grew M abscessus. Treatment of cutaneous infections from this
      organism includes debridement, culture of the organism, appropriate antibiotics,
      and wound care. 

PMID- 25942685
TI  - Pressure-sensing devices for assessment of soft tissue loading under bony
      prominences: technological concepts and clinical utilization.
AB  - Pressure-related chronic wounds, such as diabetic neuropathic foot ulcers and
      pressure ulcers, are an important health concern that affect millions of patients
      and accumulate billions in annual costs. Pressure-related chronic wounds may
      occur when soft tissues are mechanically compressed between bony prominences and
      a supporting surface. Interface pressure measurements allow the determination of
      the spatial and temporal mechanical loads that are transferred to soft tissues.
      These measurements are a basic engineering tool for evaluating the susceptibility
      of an individual to suffer a pressure-related wound. The purpose of this review
      is to: 1) describe the current techniques for body-support interface pressure
      measurements, 2) list the pressure value ranges measured under the foot in
      standing and walking, and under the buttocks in sitting (with particular emphasis
      on abnormal alterations in foot pressures as a result of diabetic neuropathy and
      alterations in sitting pressures in paralyzed patients), and 3) discuss clinical
      utilization of interface pressure measurements in the fitting of diabetic
      footwear and wheelchair cushions. 

PMID- 25942686
TI  - Healthcare professionals' and policy makers' views on implementing a clinical
      practice guideline of hypertension management: a qualitative study.
AB  - INTRODUCTION: Most studies have reported barriers to guideline usage mainly from
      doctors' perspective; few have reported the perspective of other stakeholders.
      This study aimed to determine the views and barriers to adherence of a national
      clinical practice guideline (CPG) on management of hypertension from the
      perspectives of policymakers, doctors and allied healthcare professionals.
      METHODS: This study used a qualitative approach with purposive sampling. Seven in
      depth interviews and six focus group discussions were conducted with 35
      healthcare professionals (policy makers, doctors, pharmacists and nurses) at a
      teaching hospital in Kuala Lumpur, Malaysia, between February and June 2013. All
      interviews were audio-recorded, transcribed verbatim and checked. Thematic
      approach was used to analyse the data. RESULTS: Two main themes and three sub
      themes emerged from this study. The main themes were (1) variation in the use of
      CPG and (2) barriers to adherence to CPG. The three sub-themes for barriers were
      issues inherent to the CPG, systems and policy that is not supportive of CPG use,
      and attitudes and behaviour of stakeholders. The main users of the CPG were the
      primary care doctors. Pharmacists only partially use the guidelines, while nurses
      and policy makers were not using the CPG at all. Participants had suggested few
      strategies to improve usage and adherence to CPG. First, update the CPG regularly
      and keep its content simple with specific sections for allied health workers.
      Second, use technology to facilitate CPG accessibility and provide protected time
      for implementation of CPG recommendations. Third, incorporate local CPG in
      professional training, link CPG adherence to key performance indicators and
      provide incentives for its use. CONCLUSIONS: Barriers to the use of CPG
      hypertension management span across all stakeholders. The development and
      implementation of CPG focused mainly on doctors with lack of involvement of other
      healthcare stakeholders. Guidelines should be made simple, current, reliable,
      accessible, inclusive of all stakeholders and with good policy support.

PMID- 25942687
TI  - RLT-S: A Web System for Record Linkage.
AB  - BACKGROUND: Record linkage integrates records across multiple related data
      sources identifying duplicates and accounting for possible errors. Real life
      applications require efficient algorithms to merge these voluminous data sources
      to find out all records belonging to same individuals. Our recently devised
      highly efficient record linkage algorithms provide best-known solutions to this
      challenging problem. METHOD: We have developed RLT-S, a freely available web
      tool, which implements our single linkage clustering algorithm for record
      linkage. This tool requires input data sets and a small set of configuration
      settings about these files to work efficiently. RLT-S employs exact match
      clustering, blocking on a specified attribute and single linkage based
      hierarchical clustering among these blocks. RESULTS: RLT-S is an implementation
      package of our sequential record linkage algorithm. It outperforms previous best
      known implementations by a large margin. The tool is at least two times faster
      for any dataset than the previous best-known tools. CONCLUSIONS: RLT-S tool
      implements our record linkage algorithm that outperforms previous best-known
      algorithms in this area. This website also contains necessary information such as
      instructions, submission history, feedback, publications and some other sections
      to facilitate the usage of the tool. AVAILABILITY: RLT-S is integrated into
      http://www.rlatools.com, which is currently serving this tool only. The tool is
      freely available and can be used without login. All data files used in this paper
      have been stored in https://github.com/abdullah009/DataRLATools. For copies of
      the relevant programs please see https://github.com/abdullah009/RLATools.

PMID- 25942689
TI  - Phytoremediation of Metal Contaminated Soil Using Willow: Exploiting Plant
      Associated Bacteria to Improve Biomass Production and Metal Uptake.
AB  - Short rotation coppice (SRC) of willow and poplar is proposed for economic
      valorization and concurrently as remediation strategy for metal contaminated land
      in northeast-Belgium. However, metal phytoextraction appears insufficient to
      effectuate rapid reduction of soil metal contents. To increase both biomass
      production and metal accumulation of SRC, two strategies are proposed: (i) in
      situ selection of the best performing clones and (ii) bioaugmentation of these
      clones with beneficial plant-associated bacteria. Based on field data, two
      experimental willow clones, a Salix viminalis and a Salix alba x alba clone, were
      selected. Compared to the best performing commercial clones, considerable
      increases in stem metal extraction were achieved (up to 74% for Cd and 91% for
      Zn). From the selected clones, plant-associated bacteria were isolated and
      identified. All strains were subsequently screened for their plant growth
      promoting and metal uptake enhancing traits. Five strains were selected for a
      greenhouse inoculation experiment with the selected clones planted in Cd-Zn-Pb
      contaminated soil. Extraction potential tended to increase after inoculation of
      S. viminalis plants with a Rahnella sp. strain due to a significantly increased
      twig biomass. However, although bacterial strains showing beneficial traits in
      vitro were used for inoculation, increments in extraction potential were not
      always observed. 

PMID- 25942690
TI  - Bullous hemorrhagic dermatosis induced by enoxaparin.
AB  - The bullous hemorrhagic dermatosis induced by enoxaparin is a rare adverse
      reaction, which may be under-reported given its favorable evolution. We report a
      71-year-old man who developed hemorrhagic bullae at sites distant from
      subcutaneous enoxaparin injections. It is important that clinicians be aware of
      the different adverse reactions of these widely used drugs. 

PMID- 25942691
TI  - Effect of oral photochemotherapy (8-methoxypsoralen + UVA) on the
      electrophysiologic function of retina.
AB  - CONTEXT: Since we had observed electroretinographic (ERG) abnormalities in some
      patients undergoing photochemotherapy with normal eye examination, we decided to
      investigate the effects of this therapy on retinal function. OBJECTIVE: To
      investigate the effects of oral photochemotherapy (8-methoxypsoralen +
      Ultraviolet-A) on electrophysiologic function of retina. MATERIALS AND METHODS:
      Patients with vitiligo, psoriasis or eczema were enrolled. Patients with any
      abnormal eye exam or a positive drug or family history for retinal disease were
      excluded. Baseline standard ERG was provided with the RETIport32 device. The
      second ERG was performed 6 months after the first and at least 1 week after the
      last photochemotherapy session (mean number of sessions: 45 +/- 11). The outcome
      measures were changes in rod response, standard combined response, single-flash
      cone response, 30-Hz flicker (N1-P1) and oscillatory potentials amplitudes.
      RESULTS: Forty patients were enrolled; 20 of them (mean age: 31.1 +/- 12 years)
      completed the study. The mean rod response b-wave amplitude decreased from 88.9
      +/- 47.5 to 86.4 +/- 36.6 and standard combined response b-wave amplitude
      decreased from 266.52 to 261.85 uV (p = 0.422 and p = 0.968, respectively) and
      the standard combined response a-wave amplitude increased from 155.4 +/- 40.0 at
      baseline to 165.1 +/- 48.4 in the follow-up ERG (p = 0.092). The mean single
      flash cone response a-wave amplitude decreased insignificantly in the follow-up
      ERG trace (34.5 +/- 13.7 and 29 +/- 15.4, respectively, p = 0.242). The mean
      single-flash cone response b-wave amplitude showed an insignificant increase (p =
      0.087). The amplitudes of 30-Hz flicker wave and oscillatory potentials did not
      change significantly in the follow-up ERG (p = 0.551 and p = 0.739,
      respectively). CONCLUSION: Since no significant change in ERG traces was
      observed, oral photochemotherapy seems safe for retinal electrophysiologic
      function.

PMID- 25942688
TI  - Growth factors for the treatment of ischemic brain injury (growth factor
      treatment).
AB  - In recent years, growth factor therapy has emerged as a potential treatment for
      ischemic brain injury. The efficacy of therapies that either directly introduce
      or stimulate local production of growth factors and their receptors in damaged
      brain tissue has been tested in a multitude of models for different Central
      Nervous System (CNS) diseases. These growth factors include erythropoietin (EPO),
      vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor
      (BDNF), and insulin-like growth factor (IGF-1), among others. Despite the promise
      shown in animal models, the particular growth factors that should be used to
      maximize both brain protection and repair, and the therapeutic critical period,
      are not well defined. We will review current pre-clinical and clinical evidence
      for growth factor therapies in treating different causes of brain injury, as well
      as issues to be addressed prior to application in humans. 

PMID- 25942692
TI  - Traffic fatality indicators in Brazil: State diagnosis based on data envelopment
      analysis research.
AB  - The intense economic growth experienced by Brazil in recent decades and its
      consequent explosive motorization process have evidenced an undesirable impact:
      the increasing and unbroken trend in traffic fatality numbers. In order to
      contribute to road safety diagnosis on a national level, this study presents a
      research into two main indicators available in Brazil: mortality rate
      (represented by fatalities per capita) and fatality rate (represented by two sub
      indicators, i.e., fatalities per vehicle and fatalities per vehicle kilometer
      traveled). These indicators were aggregated into a composite indicator or index
      through a multiple layer data envelopment analysis (DEA) composite indicator
      model, which looks for the optimum combination of indicators' weights for each
      decision-making unit, in this case 27 Brazilian states. The index score
      represents the road safety performance, based on which a ranking of states can be
      made. Since such a model has never been applied for road safety evaluation in
      Brazil, its parameters were calibrated based on the experience of more
      consolidated European Union research in ranking its member countries using DEA
      techniques. Secondly, cluster analysis was conducted aiming to provide more
      realistic performance comparisons and, finally, the sensitivity of the results
      was measured through a bootstrapping method application. It can be concluded that
      by combining fatality indicators, defining clusters and applying bootstrapping
      procedures a trustworthy ranking can be created, which is valuable for nationwide
      road safety planning. 

PMID- 25942694
TI  - Interactive Instrument-Driven Image Display in Laparoscopic Surgery.
AB  - BACKGROUND: A significant limitation of minimally invasive surgery is dependence
      of the entire surgical team on a single endoscopic viewpoint. An individualized,
      instrument-driven image display system that allows all operators to
      simultaneously define their viewing frame of the surgical field may be the
      solution. We tested the efficacy of such a system using a modified Fundamentals
      of Laparoscopic SurgeryTM (Society of American Gastrointestinal and Endoscopic
      Surgeons, Los Angeles, CA) bead transfer task. MATERIALS AND METHODS: A program
      was custom-written to allow zooming and centering of the image window on specific
      color signals, each attached near the tip of a different laparoscopic instrument.
      Two controls were used for the bead transfer task: (1) a static, wide-angle view
      and (2) a single moving camera allowing close-up and tracking of the bead as it
      was transferred. Time to task completion and number of bead drops were recorded.
      RESULTS: Thirty-six sessions were performed by surgical residents. Average time
      for bead transfer was 127.3+/-21.3 seconds in the Experimental group, 139.1+/
      27.8 seconds in the Control 1 group, and 186.2+/-18.5 seconds in the Control 2
      group (P=.034, by analysis of variance). Paired analysis (the Wilcoxon Signed
      Rank Test) showed that the Experimental group was significantly faster than the
      Control 1 group (P=.035) and the Control 2 group (P=.028). CONCLUSIONS: We have
      developed an image navigation system that allows intuitive and efficient
      laparoscopic performance compared with two controls. It offers high-resolution
      images and ability for multitasking. The tracking system centers close-up images
      on the laparoscopic target. Further development of robust prototypes will help
      transition this in vitro system into clinical application.

PMID- 25942693
TI  - How RIG-I like receptors activate MAVS.
AB  - RIG-I and MDA5 are well-conserved cytoplasmic pattern recognition receptors that
      detect viral RNAs during infection and activate the type I interferon (IFN)
      mediated antiviral immune response. While much is known about how these receptors
      recognize viral RNAs, how they interact with their common signaling adaptor
      molecule MAVS and activate the downstream signaling pathway had been less clear.
      Previous studies have shown that the signaling domains (tandem CARDs or 2CARDs)
      of RIG-I and MDA5 must form homo-oligomers in order to interact with MAVS, and
      that their interactions lead to filament formation of MAVS, a pre-requisite for
      downstream signal activation. More recent data suggest that multiple mechanisms
      synergistically promote tetramer formation of RIG-I 2CARD, and that this tetramer
      resembles a lock-washer, which serves as a helical template to nucleate the MAVS
      filament. We here summarize these recent findings and discuss the current
      understanding of the signal activation mechanisms of RIG-I and MDA5. 

PMID- 25942695
TI  - Diffusion and leachability index studies on stabilization of chromium
      contaminated soil using fly ash.
AB  - Experiments were performed to establish a feasible treatment process for the
      solidification and stabilization (S/S) of soil contaminated by leaching of Cr(VI)
      from Chromite ore processing residue (COPR). Reduction of the highly mobile
      Cr(VI) was performed using calcium polysulfide (CaS5) with a dosage of 3 times
      the molar stoichiometric ratio for the initial concentration of Cr(VI) present in
      the chromium contaminated soil (CCS). The CCS was solidified and stabilized (S/S)
      using fly ash (FA) in various proportions i.e., 1:1, 1:2, 1:3 (FA: CCS) with and
      without using reducing agent i.e., CaS5. Leachability tests such as Toxicity
      Characteristic Leaching Procedure (TCLP) and semi-dynamic long term leachability
      tests indicated that the CaS5 was effective in reduction of Cr(VI) followed by
      the S/S process. Leachability Index was derived from the results of the semi
      dynamic long term leachability tests and was between 8 and 9, indicating that FA
      is an effective treatment for disposal into secured landfills for CCS. The
      characteristic compressive strength of the CaS5 treated CCS with FA mortar blocks
      were between 24.47 and 40.49 kg/cm(2). Considering the cost of CaS5 and FA, a
      total expenditure of Rs. 7826 i.e., US $ 130.4 would be required for remediation
      of one tonne of CCS.

PMID- 25942696
TI  - Fabrication of fibrous amidoxime-functionalized mesoporous silica microsphere and
      its selectively adsorption property for Pb(2+) in aqueous solution.
AB  - Fibrous cyano-modified mesoporous SiO2 microspheres with specific surface area of
      ca. 300 m(2) g(-1) have been successfully fabricated respectively by in-situ
      synthesis and post-modification methods, based on the hydrolysis of ethyl
      silicate in the presence of (2-cyanoethyl)triethoxysilane at a certain condition.
      TEM observations show that the average diameters of the prepared fibrous cyano
      modified SiO2 microspheres by these two methods are 68 and 211 nm, respectively.
      The N2 adsorption-desorption isotherms analysis on the fibrous SiO2 microspheres
      show sharp peaks in the 10-20 nm range. After the cyano groups transformed to
      amidoxime groups, the adsorption behavior of the fibrous amidoxime-functionalized
      mesoporous SiO2 microspheres for Fe(3+), Cu(2+), and Pb(2+) was investigated. The
      results show that the prepared SiO2 microspheres can selectively adsorb Pb(2+).
      The maximum equilibrium adsorption capacity for Pb(2+) could reach 284 mg/g. The
      desorption of Pb(2+) in 2M HNO3 completes within 60 min. The efficiency of the
      desorption is as high as 96.2%. This work provides the methods to prepare
      amidoxime-functionalized SiO2 microsphere with high specific surface area and
      total pore volume, which has the potential to be applied as an efficient
      adsorbent for specific heavy metal ions.

PMID- 25942697
TI  - Solvent-free synthesis and application of nano-Fe/Ca/CaO/[PO4] composite for dual
      separation and immobilization of stable and radioactive cesium in contaminated
      soils.
AB  - This study assessed the synthesis and application of nano-Fe/Ca/CaO-based
      composite material for use as a separation and immobilizing treatment of dry soil
      contaminated by stable ((133)Cs) and radioactive cesium species ((134)Cs and
      (137)Cs). After grinding with nano-Fe/CaO, nano-Fe/Ca/CaO, and nano
      Fe/Ca/CaO/[PO4], approximately 31, 25, and 22 wt% of magnetic fraction soil was
      separated. Their resultant (133)Cs immobilization values were about 78, 81, and
      100%, respectively. When real radioactive cesium contaminated soil obtained from
      Fukushima was treated with nano-Fe/Ca/CaO/[PO4], approximately 27.3 wt% of
      magnetic and 72.75% of non-magnetic soil fractions were separated. The highest
      amount of entrapped (134)Cs and (137)Cs was found in the lowest weight of the
      magnetically separated soil fraction (i.e., 80% in 27.3% of treated soil).
      Results show that (134)Cs and (137)Cs either in the magnetic or non-magnetic soil
      fractions was 100% immobilized. The morphology and mineral phases of the nano
      Fe/Ca/CaO/[PO4] treated soil were characterized using SEM-EDS, EPMA, and XRD
      analysis. The EPMA and XRD patterns indicate that the main fraction of
      enclosed/bound materials on treated soil included Ca/PO4 associated crystalline
      complexes. These results suggest that simple grinding treatment with nano
      Fe/Ca/CaO/[PO4] under dry conditions might be an extremely efficient separation
      and immobilization method for radioactive cesium contaminated soil.

PMID- 25942698
TI  - Differential contribution of frugivorous birds to dispersal patterns of the
      endangered Chinese yew (Taxus chinensis).
AB  - The contribution of forest generalists and specialists to the dispersal pattern
      of tree species is not well understood. Specialists are considered low-quality
      dispersers because their dispersal distance is often short. However, disregard
      for seed deposition site may result in underestimation of the dispersal quality
      of specialists. The present study estimated the contribution of generalist and
      specialist species to the dispersal patterns of the endangered Chinese yew (Taxus
      chinensis) in a subtropical patchy forest in Southeast China. A relatively
      diverse assemblage of frugivorous birds visited T. chinensis source trees, and
      specialist Hypsipetes leucocephalus and generalist Urocissa erythrorhyncha were
      by far the highest-quantity dispersers. Considering dispersal effectiveness, the
      quantity aspect of effectiveness differed between the specialist assemblage and
      generalist assemblage; the contribution of specialists to the quantity part of
      effectiveness was significantly higher than that of generalists despite the
      relatively low diversity of specialists. After foraging, both specialist H.
      leucocephalus and generalist U. erythrorhyncha significantly contributed to the
      number of seedlings, and their contributions to seedling recruitment did not
      differ with regard to quality. Our results highlight the ability of T. chinensis
      to recruit an effective disperser assemblage in patchy habitats, thus increasing
      its persistence in this disturbed habitat. 

PMID- 25942699
TI  - Theoretical study of the oxidation mechanisms of naphthalene initiated by
      hydroxyl radicals: the O2 addition reaction pathways.
AB  - Atmospheric oxidation of the naphthalene-OH adduct [C10H8OH] (R1) by molecular
      oxygen in its triplet electronic ground state has been studied using density
      functional theory along with the B3LYP, omegaB97XD, UM05-2x and UM06-2x exchange
      correlation functionals. From a thermodynamic viewpoint, the most favourable
      process is O2 addition at the C2 position in syn mode, followed by O2 addition at
      the C2 position in anti mode, O2 addition at the C4 position in syn mode, and O2
      addition at the C4 position in anti mode, as the second, third and fourth most
      favourable processes. The syn modes of addition at these positions are
      thermodynamically favoured over the anti ones by the formation of an
      intramolecular hydrogen bond between the hydroxyl and peroxy substituents.
      Analysis of the computed structures, bond orders and free energy profiles
      demonstrate that the reaction steps involved in the oxidation of the naphthalene
      OH adduct by O2 satisfy Hammond's principle. Kinetic rate constants and branching
      ratios under atmospheric pressure and in the fall-off regime have been supplied,
      using transition state and RRKM theories. By comparison with experiment, these
      data confirm the relevance of a two-step reaction mechanism. Whatever the
      addition mode, O2 addition in C4 position is kinetically favoured over O2
      addition in C2 position, in contrast with the expectations drawn from
      thermodynamics and reaction energies. Under a kinetic control of the reaction,
      and in line with the computed reaction energy barriers, the most efficient
      process is O2 addition at the C4 position in syn mode, followed by O2 addition at
      the C2 position in syn mode, O2 addition at the C4 position in anti mode, and O2
      addition at the C2 position in anti mode as the second, third and fourth most
      rapid processes. The computed branching ratios also indicate that the
      regioselectivity of the reaction decreases with increasing temperatures and
      decreasing pressures. 

PMID- 25942700
TI  - Growth arrest and rapid capture of select pathogens following magnetic
      nanoparticle treatment.
AB  - Thorough understanding of magnetic nanoparticle (MNP) properties is essential for
      developing new theranostics. In this study, we provide evidence that non-modified
      magnetic iron oxide nanoparticles and their functionalized derivatives may be
      used to restrict growth and capture different pathogens. Coprecipitation of
      Fe(2+) and Fe(3+) ions in an alkaline solution was used to synthesize MNPs that
      subsequently were functionalized by gold and aminosilane coating. Transmission
      electron microscopy (TEM), differential scanning calorimetry (DSC) and Fourier
      transform infrared spectroscopy (FT-IR) were used to assess their physicochemical
      properties. A significant decrease of Escherichia coli, Staphylococcus aureus,
      Pseudomonas aeruginosa and Candida albicans outgrown from medium after addition
      of MNPs or their derivatives was observed during 24h culture. Measurement of
      optical density revealed that using MNPs, these pathogens can be quickly captured
      and removed (with efficiency reaching almost 100%) from purposely infected saline
      buffer and body fluids such as human blood plasma, serum, abdominal fluids and
      cerebrospinal fluids. These effects depend on nanoparticle concentration, surface
      chemistry, the type of pathogen, as well as the surrounding environment. 

PMID- 25942701
TI  - Use of Animal Models in Plant Sterol and Stanol Research.
AB  - Cholesterol-lowering properties of plant sterols were reported approximately six
      decades ago. However, over the past couple of decades we have learnt more about
      other cardiovascular benefits of regular consumption of plant sterols and/or
      plant stanols. In particular a series of animal studies has consistently reported
      that dietary plant sterols and/or plant stanols or their fatty acid esters can
      reduce atherogenesis to a different extent in different animal models. Such
      effects may be mediated not only through reductions in LDL cholesterol levels,
      but also through other mechanisms including anti-inflammatory effects. In this
      manuscript, various animal models including mice, rabbits, hamsters, and others
      which have been used to establish cardiovascular benefits of plant sterols are
      discussed. 

PMID- 25942702
TI  - Mitochondria-targeting nanoplatform with fluorescent carbon dots for long time
      imaging and magnetic field-enhanced cellular uptake.
AB  - In this study, a biocompatible nanoplatform has been constructed on the basis of
      magnetic mesoporous silica nanoparticles (Fe3O4@mSiO2) via surface modification
      of triphenylphospine (TPP) and then conjugation with fluorescent carbon dots
      (CDs). The as-prepared Fe3O4@mSiO2-TPP/CDs nanoplatform shows a very low
      cytotoxicity and apoptosis rate in various cell lines such as A549, CHO, HeLa, SH
      SY5Y, HFF, and HMEC-1. More importantly, this nanoplatform integrates long time
      cell imaging, mitochondria-targeting, and magnetic field-enhanced cellular uptake
      functionalities into an all-in-one system. Time-dependent mitochondrial
      colocalization in all of the cell lines has been proved by using confocal laser
      scanning microscopy and flow cytometry, while the multicolored fluorescence of
      the Fe3O4@mSiO2-TPP/CDs could remain bright and stable after coincubation for 24
      h. In addition, the cellular uptake efficiency could be enhanced in a short time
      as a static magnetic field of 0.30 T was applied to the coincubation system of
      A549 and HFF cell lines. This bionanoplatform may have potential applications in
      targeted drug delivery for mitochondria diseases as well as early cancer
      diagnosis and treatment. 

PMID- 25942703
TI  - Circumcision Status and Risk of HIV Acquisition during Heterosexual Intercourse
      for Both Males and Females: A Meta-Analysis.
AB  - In this study, we evaluated if male circumcision was associated with lower HIV
      acquisition for HIV (-) males and HIV (-) females during normal sexual behavior.
      We performed a systematic literature search of PubMed, EMBASE, and Cochrane
      Central Register of Controlled Trials (CENTRAL) databases to identify studies
      that compared HIV acquisition for the circumcised and uncircumcised groups. The
      reference lists of the included and excluded studies were also screened. Fifteen
      studies (4 RCTs and 11 prospective cohort studies) were included, and the related
      data were extracted and analyzed in a meta-analysis. Our study revealed strong
      evidence that male circumcision was associated with reduced HIV acquisition for
      HIV(-) males during sexual intercourse with females [pooled adjusted risk ratio
      (RR): 0.30, 95% CI 0.24 0.38, P < 0.00001] and provided a 70% protective effect.
      In contrast, no difference was detected in HIV acquisition for HIV (-) females
      between the circumcised and uncircumcised groups (pooled adjusted RR after
      sensitivity analysis: 0.68, 95%CI 0.40-1.15, P = 0.15). In conclusion, male
      circumcision could significantly protect males but not females from HIV
      acquisition at the population level. Male circumcision may serve as an additional
      approach toward HIV control, in conjunction with other strategies such as HIV
      counseling and testing, condom promotion, and so on. 

PMID- 25942704
TI  - IBD. Fishing for missing heritability in IBD.
AB  - A genetic predisposition to IBD is widely accepted; however IBD heritability is
      dependent on more than the simple additive risk of genetic variants. In a new
      study using zebrafish, convincing evidence is presented that alterations in the
      epigenetic regulation of TNF might contribute to the "missing heritability" of
      IBD.

PMID- 25942705
TI  - The Atherogenicity of Plant Sterols: The Evidence from Genetics to Clinical
      Trials.
AB  - The human diet is naturally varied and contains not only essential nutrients, but
      also contains molecules that the body actively excludes or minimizes exposure.
      Among these molecules are xenosterols, of which plant sterols comprise the
      greatest exposure risk. These sterols comprise approximately 50% of the total
      sterols we eat, yet we retain <0.5% of these in our bodies. The bulk of this
      exclusion takes place in the intestine and the heterodimeric transporters ABCG5
      and ABCG8 are key to keeping these xenosterols out of our bodies. In normal
      humans, pharmacological supplementation with plant sterols (and stanols) has been
      used to lower cholesterol as these impair intestinal absorption/ re-absorption of
      this molecule; lowering plasma cholesterol has cardiovascular risk benefits. This
      review challenges whether this intervention is beneficial and may even be
      harmful. We summarize the evidence involving humans who have genetic disruption
      of ABCG5/ABCG8 function, from clinical trial data examining plant sterols and
      cardiovascular risk, from genetic data affecting normal humans and ABCG5/ABCG8
      variations to data obtained using animal models. Accumulation of xenosterols in
      any significant amount is clearly associated with increased toxicity, and data
      suggest that at even low levels there may be effects. Importantly, there is also
      a paucity of data showing cardiovascular end-point benefits with plant
      sterol/stanol supplementation. The summary of evidence highlights not only
      caution in recommending such strategies to lower plasma cholesterol, but also in
      investigating how these xenosterols can affect processes ranging from
      cardiovascular, endocrine, and neurological function. 

PMID- 25942708
TI  - Bay Bridge anchorage construction: George Booth Post.

PMID- 25942709
TI  - Unraveling the influence of gut microbes on the mind.

PMID- 25942710
TI  - Innovating care for Medicare beneficiaries: time for riskier bets and embracing
      failure.

PMID- 25942719
TI  - An Affordable Care Act at year 5: key issues for improvement.

PMID- 25942720
TI  - A piece of my mind. The hero in medicine.

PMID- 25942721
TI  - Continued progress against hepatitis C infection.

PMID- 25942722
TI  - Administration of spores of nontoxigenic Clostridium difficile strain M3 for
      prevention of recurrent C. difficile infection: a randomized clinical trial.
AB  - IMPORTANCE: Clostridium difficile is the most common cause of health care
      associated infection in US hospitals. Recurrence occurs in 25% to 30% of
      patients. OBJECTIVE: To determine the safety, fecal colonization, recurrence
      rate, and optimal dosing schedule of nontoxigenic C. difficile strain M3
      (VP20621; NTCD-M3) for prevention of recurrent C. difficile infection (CDI).
      DESIGN, SETTING, AND PARTICIPANTS: Phase 2, randomized, double-blind, placebo
      controlled, dose-ranging study conducted from June 2011 to June 2013 among 173
      patients aged 18 years or older who were diagnosed as having CDI (first episode
      or first recurrence) and had successfully completed treatment with metronidazole,
      oral vancomycin, or both at 44 study centers in the United States, Canada, and
      Europe. INTERVENTIONS: Patients were randomly assigned to receive 1 of 4
      treatments: oral liquid formulation of NTCD-M3, 10(4) spores/d for 7 days (n =
      43), 10(7) spores/d for 7 days (n = 44), or 10(7) spores/d for 14 days (n = 42),
      or placebo for 14 days (n = 44). MAIN OUTCOMES AND MEASURES: The primary outcome
      was safety and tolerability of NTCD-M3 within 7 days of treatment. Exploratory
      secondary outcomes included fecal colonization with NTCD-M3 from end of study
      drug through week 6 and CDI recurrence from day 1 through week 6. RESULTS: Among
      168 patients who started treatment, 157 completed treatment. One or more
      treatment-emergent adverse events were reported in 78% of patients receiving NTCD
      M3 and 86% of patients receiving placebo. Diarrhea and abdominal pain were
      reported in 46% and 17% of patients receiving NTCD-M3 and 60% and 33% of placebo
      patients, respectively. Serious treatment-emergent adverse events were reported
      in 7% of patients receiving placebo and 3% of all patients who received NTCD-M3.
      Headache was reported in 10% of patients receiving NTCD-M3 and 2% of placebo
      patients. Fecal colonization occurred in 69% of NTCD-M3 patients: 71% with 10(7)
      spores/d and 63% with 10(4) spores/d. Recurrence of CDI occurred in 13 (30%) of
      43 placebo patients and 14 (11%) of 125 NTCD-M3 patients (odds ratio [OR], 0.28;
      95% CI, 0.11-0.69; P = .006); the lowest recurrence was in 2 (5%) of 43 patients
      receiving 10(7) spores/d for 7 days (OR, 0.1; 95% CI, 0.0-0.6; P = .01 vs
      placebo]). Recurrence occurred in 2 (2%) of 86 patients who were colonized vs 12
      (31%) of 39 patients who received NTCD-M3 and were not colonized (OR, 0.01; 95%
      CI, 0.00-0.05; P < .001). CONCLUSIONS AND RELEVANCE: Among patients with CDI who
      clinically recovered following treatment with metronidazole or vancomycin, oral
      administration of spores of NTCD-M3 was well tolerated and appeared to be safe.
      Nontoxigenic C. difficile strain M3 colonized the gastrointestinal tract and
      significantly reduced CDI recurrence. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT01259726.

PMID- 25942724
TI  - Daclatasvir in combination with asunaprevir and beclabuvir for hepatitis C virus
      genotype 1 infection with compensated cirrhosis.
AB  - IMPORTANCE: Effective and well-tolerated, interferon-free regimens are needed for
      treatment of patients with chronic hepatitis C virus (HCV) infection and
      cirrhosis. OBJECTIVE: All-oral therapy with daclatasvir (nonstructural protein 5A
      [NS5A] inhibitor), asunaprevir (NS3 protease inhibitor), and beclabuvir
      (nonnucleoside NS5B inhibitor), with or without ribavirin, was evaluated in
      patients with HCV genotype 1 infection and compensated cirrhosis. DESIGN,
      SETTING, AND PARTICIPANTS: The UNITY-2 study was conducted between December 2013
      and October 2014 at 49 outpatient sites in the United States, Canada, France, and
      Australia. Patients were treated for 12 weeks, with 24 weeks of follow-up after
      completion of treatment. Adult patients with cirrhosis were enrolled in 2
      cohorts: HCV treatment-naive or HCV treatment-experienced. Statistical analyses
      were based on historical controls; there were no internal controls.
      INTERVENTIONS: All patients received twice-daily treatment with the fixed-dose
      combination of daclatasvir (30 mg), asunaprevir (200 mg), and beclabuvir (75 mg).
      In addition, patients within each cohort were stratified according to HCV
      genotype 1 subtype (1a or 1b) and randomly assigned (1:1) to receive double
      blinded weight-based ribavirin (1000-1200 mg/d) or matching placebo. MAIN
      OUTCOMES AND MEASURES: Sustained virologic response at posttreatment week 12
      (SVR12). RESULTS: One hundred twelve patients in the treatment-naive group and 90
      patients in the treatment-experienced group were treated and included in the
      analysis. Enrolled patients were 88% white with a median age of 58 years
      (treatment-naive group) or 60 years (treatment-experienced group); 74% had
      genotype 1a infection. SVR12 rates were 98% (97.5% CI, 88.9%-100%) for patients
      in the treatment-naive group and 93% (97.5% CI, 85.0%-100.0%) for those in the
      treatment-experienced group when ribavirin was included in the regimen. With the
      fixed-dose combination alone, response rates were 93% (97.5% CI, 85.4%-100.0%)
      for patients in the treatment-naive group and 87% (97.5% CI, 75.3%-98.0%) for
      those in the treatment-experienced group. Three serious adverse events were
      considered to be treatment related and there were 4 adverse event-related
      discontinuations. Treatment-emergent grade 3 or 4 alanine aminotransferase
      elevations were observed in 4 patients, of which 1 had concomitant total
      bilirubin elevation. CONCLUSIONS AND RELEVANCE: In this open-label uncontrolled
      study, patients with chronic HCV genotype 1 infection and cirrhosis who received
      a 12-week oral fixed-dose regimen of daclatasvir, asunaprevir, and beclabuvir,
      with or without ribavirin, achieved high rates of SVR12.

PMID- 25942725
TI  - Ramelteon for prevention of delirium in hospitalized older patients.

PMID- 25942723
TI  - Fixed-dose combination therapy with daclatasvir, asunaprevir, and beclabuvir for
      noncirrhotic patients with HCV genotype 1 infection.
AB  - IMPORTANCE: The antiviral activity of all-oral, ribavirin-free, direct-acting
      antiviral regimens requires evaluation in patients with chronic hepatitis C virus
      (HCV) infection. OBJECTIVE: To determine the rates of sustained virologic
      response (SVR) in patients receiving the 3-drug combination of daclatasvir (a pan
      genotypic NS5A inhibitor), asunaprevir (an NS3 protease inhibitor), and
      beclabuvir (a nonnucleoside NS5B inhibitor). DESIGN, SETTING, AND PARTICIPANTS:
      This was an open-label, single-group, uncontrolled international study (UNITY-1)
      conducted at 66 sites in the United States, Canada, France, and Australia between
      December 2013 and August 2014. Patients without cirrhosis who were either
      treatment-naive (n = 312) or treatment-experienced (n = 103) and had chronic HCV
      genotype 1 infection were included. INTERVENTIONS: Patients received a twice
      daily fixed-dose combination of daclatasvir, 30 mg; asunaprevir, 200 mg; and
      beclabuvir, 75 mg. MAIN OUTCOMES AND MEASURES: The primary study outcome was
      SVR12 (HCV-RNA <25 IU/mL at posttreatment week 12) in patients naive to
      treatment. A key secondary outcome was SVR12 in the treatment-experienced cohort.
      RESULTS: Baseline characteristics were comparable between the treatment-naive and
      treatment-experienced cohorts. Patients were 58% male, 26% had IL28B (rs12979860)
      CC genotype, 73% were infected with genotype 1a, and 27% were infected with
      genotype 1b. Overall, SVR12 was observed in 379 of 415 patients (91.3%; 95% CI,
      88.6%-94.0%): 287 of 312 treatment-naive patients (92.0%; 95% CI, 89.0%-95.0%)
      and 92 of 103 treatment-experienced patients (89.3%; 95% CI, 83.4%-95.3%).
      Virologic failure occurred in 34 patients (8%) overall. One patient died at
      posttreatment week 3; this was not considered related to study medication. There
      were 7 serious adverse events, all considered unrelated to study treatment, and 3
      adverse events (<1%) leading to treatment discontinuation, including 2 grade 4
      alanine aminotransferase elevations. The most common adverse events (in >=10% of
      patients) were headache, fatigue, diarrhea, and nausea. CONCLUSIONS AND
      RELEVANCE: In this open-label, nonrandomized, uncontrolled study, a high rate of
      SVR12 was achieved in treatment-naive and treatment-experienced noncirrhotic
      patients with chronic HCV genotype 1 infection who received 12 weeks of treatment
      with the oral fixed-dose regimen of daclatasvir, asunaprevir, and beclabuvir.
      TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01979939.

PMID- 25942726
TI  - Tattoo rash.

PMID- 25942727
TI  - Testosterone levels for evaluation of androgen deficiency.

PMID- 25942728
TI  - Hospitalization for pneumonia and risk of cardiovascular disease.

PMID- 25942729
TI  - Hospitalization for pneumonia and risk of cardiovascular disease--reply.

PMID- 25942730
TI  - Sedation protocol for critically ill pediatric patients.

PMID- 25942731
TI  - Sedation protocol for critically ill pediatric patients--reply.

PMID- 25942732
TI  - Expanding long-term care options for persons with serious mental illness.

PMID- 25942733
TI  - Expanding long-term care options for persons with serious mental illness.

PMID- 25942734
TI  - Expanding long-term care options for persons with serious mental illness.

PMID- 25942735
TI  - Expanding long-term care options for persons with serious mental illness.

PMID- 25942736
TI  - Expanding long-term care options for persons with serious mental illness.

PMID- 25942737
TI  - Expanding long-term care options for persons with serious mental illness--reply.

PMID- 25942738
TI  - Incorrect alignment and omitted data in tables.

PMID- 25942739
TI  - Revisions in table.

PMID- 25942741
TI  - Anatomic nomenclature.

PMID- 25942742
TI  - JAMA patient page. Male infertility.

PMID- 25942743
TI  - New particle formation and growth from methanesulfonic acid, trimethylamine and
      water.
AB  - New particle formation from gas-to-particle conversion represents a dominant
      source of atmospheric particles and affects radiative forcing, climate and human
      health. The species involved in new particle formation and the underlying
      mechanisms remain uncertain. Although sulfuric acid is commonly recognized as
      driving new particle formation, increasing evidence suggests the involvement of
      other species. Here we study particle formation and growth from methanesulfonic
      acid, trimethylamine and water at reaction times from 2.3 to 32 s where particles
      are 2-10 nm in diameter using a newly designed and tested flow system. The flow
      system has multiple inlets to facilitate changing the mixing sequence of gaseous
      precursors. The relative humidity and precursor concentrations, as well as the
      mixing sequence, are varied to explore their effects on particle formation and
      growth in order to provide insight into the important mechanistic steps. We show
      that water is involved in the formation of initial clusters, greatly enhancing
      their formation as well as growth into detectable size ranges. A kinetics box
      model is developed that quantitatively reproduces the experimental data under
      various conditions. Although the proposed scheme is not definitive, it suggests
      that incorporating such mechanisms into atmospheric models may be feasible in the
      near future. 

PMID- 25942744
TI  - Antibacterial Honey (MedihoneyTM): in-vitro Activity Against Clinical Isolates
      of MRSA, VRE, and Other Multiresistant Gram-negative Organisms Including
      Pseudomonas aeruginosa.
AB  - The clinical use of honey has received increasing interest in recent years,
      particularly its use as a topical antibacterial dressing. Results thus far are
      extremely encouraging, and demonstrate that honey is effective against a broad
      range of microorganisms, including multiresistant strains. This in-vitro study
      complements the work of others and focuses on the impact that a standardized
      honey can have on multiresistant bacteria that are regularly found in wounds and
      are responsible for increased morbidity. 

PMID- 25942745
TI  - Insights on Virulence and Antibiotic Resistance: A Review of the Accessory
      Genome of Staphylococcus aureus.
AB  - Staphylococcus aureus continues to be a serious health problem worldwide due to
      its intrinsic nature of virulence, ability to cause a wide array of infection,
      and its capacity to develop resistance to a number of antibiotics. The S aureus
      genome has continually evolved through both mutation and acquisition of exogenous
      genes, leading to the emergence of antibiotic-resistant strains with the ability
      for clonal dissemination across nations and continents. Methicillin-resistant S
      aureus (MRSA) is one of the most commonly identified antibiotic-resistant
      pathogens in the hospital and community settings with substantial mortality and
      morbidity. This review examines the accessory genome of 8 sequenced S aureus
      strains regarding the variety of virulence factors and mechanisms of antibiotic
      resistance. The remarkable nature of this organism to acquire and disseminate an
      array of mobile genetic elements (MBEs) through horizontal gene transfer
      illustrates the mechanisms for evolution and its fitness level in the face of
      constant environmental challenges. The relative ease of transfer of genetic
      materials, especially antibiotic-resistant genes, across staphylococcal species
      indicates that there is a potential pandemic problem in the hospital and
      community environment. 

PMID- 25942746
TI  - The use of elastocompressive therapy in a patient with acroangiodermatitis of
      the lower limb.
AB  - Acroangiodermatitis is a rare vasoproliferative disorder, usually affecting the
      lower limbs and is associated with congenital or acquired vascular conditions.
      There are two variants of acroangiodermatitis-Mali type (associated with venous
      hypertension) and Stewart-Bluefarb type, which is associated with arteriovenous
      malformation, or acquired iatrogenic arteriovenous fistula in patients with
      chronic renal failure. Acroangiodermatitis is clinically characterized by
      angiomatous papules and plaques, which mimics Kaposi's sarcoma. The authors
      present a case of a 63-year-old man with acroangiodermatitis of the lower limbs
      and chronic venous insufficiency who was treated with elastocompressive therapy. 

PMID- 25942747
TI  -  Negative pressure wound therapy on diabetic foot ulcer.
AB  - The effects of negative pressure wound therapy ([NPWT], V.A.C.(r) Therapy, KCI,
      San Antonio, Tex) were compared with standard dressings in 45 patients with
      diabetic foot ulcers who were admitted to the Department of Plastic and
      Reconstructive Surgery, Medical Park Hospital, Bursa, Turkey. Twenty-four
      patients were randomly divided into 2 groups-NPWT group and control group.
      Initially, the mean surface area of wounds in the NPWT group was 109 cm2, the
      control group 94.8 cm2. The mean duration of open wound care was 11.25 days in
      the NPWT group and 15.75 days in the control group (P = 0.05). After wound
      management, mean surface area of the diabetic wounds was 88.6 cm2 in the NPWT
      group, and 85.3 cm2 in the control group (P < 0.05). The use of NPWT may be an
      effective initial wound therapy to achieve faster wound bed granulation in
      diabetic foot ulcers. Further studies are needed to clarify the effects and
      indications and to modify the technique of this alternative treatment for use on
      nonhealing wounds. 

PMID- 25942748
TI  - Partial glossectomy and floor of mouth (FOM) defect repair with biological dural
      graft: A case report.
AB  - INTRODUCTION: Oral carcinoma can cause significant defects that would necessitate
      a challenging reconstructive surgery. These techniques include biological or
      synthetic dressings, grafts, regional flaps, and free-vascularized flaps. Among
      these, the dural graft has demonstrated promising results in repairing the skull
      base defects. Our aim is to report a new, innovative technique for partial
      glossectomy and floor of mouth defect repair using a biological dural graft
      dressing when primary repair was not feasible and the patient did not consent to
      dermal graft or flap interventions. PRESENTATION OF CASE: This article reports
      the outcomes from a novel intervention of partial glossectomy repair using a
      biological dural dressing derived from bovine type-I collagen in a 57-year-old
      female patient with recurrent T1N1M0 squamous cell carcinoma of the left-sided
      tongue during the 12 month period of follow-up. DISCUSSION: The best option for
      large tongue defects is a free flap, while for a moderate defect is a regional
      oral flap. The biological graft, as an acellular dermal graft has been well known
      to facilitate secondary healing in the tongue as an alternative to the split
      thickness skin graft. In the current study, the dural dressing in tongue
      reconstruction was likewise shown to be an effective biological dressing; hence,
      the collagen membrane is biologically acceptable to the oral mucosa and an
      excellent wound graft material. However, it is absolutely contraindicated in
      bovine hypersensitive patients. CONCLUSION: The biological dural graft dressing
      appears to be an effective method for tongue reconstruction, as it promotes
      adequate wound healing and it preserves function.

PMID- 25942749
TI  - Toxic megacolon during pregnancy in ulcerative colitis: A case report.
AB  - INTRODUCTION: Ulcerative colitis is an idiopathic inflammatory bowel condition
      whose peak incidence coincides with fertility in female patients. In pregnancy,
      acute fulminant colitis is rare, and, when it becomes refractory to maximum
      medical therapy, emergency colectomy is mandated. Over the past quarter century,
      there have been few reports of this rare event in the literature. PRESENTATION OF
      CASE: We report a 26 year old primigravida female who presented with toxic
      megacolon during the third trimester of pregnancy, unresponsive to medical
      therapy. She subsequently underwent an urgent low transverse caesarean section
      with a total colectomy. Both mother and child made a satisfactory recovery post
      operatively. DISCUSSION: Although the fetus is at higher risk than the mother in
      such a circumstance, morbidity and mortality rates are still noticeably high for
      both, and therefore, prompt diagnosis is key. CONCLUSION: It is imperative that
      female patients planning to conceive with a known diagnosis of ulcerative colitis
      liaise with their obstetricians and gastroenterologists early to optimise medical
      treatment to prevent the development of a toxic megacolon and that conception is
      planned during a state of remission. Should surgical intervention become
      required, this can be performed with favourable outcomes for mother and child, as
      demonstrated in this report.

PMID- 25942750
TI  - Vacuum-assisted closure for open perineal wound after abdominoperineal resection.
AB  - INTRODUCTION: In colorectal cancer surgery, surgical site infection (SSI) is a
      common complication, and especially, perineal wound complications after
      abdominoperineal resection (APR) remain to be serious clinical problems. Vacuum
      assisted closure (VAC) therapy was first reported in another surgical field in
      1997, and it is useful for treating complex wounds because it promotes
      granulation. VAC therapy has been recently used for open abdominal wounds. We
      introduced VAC for treating open perineal wound of APR and report the usefulness
      of it. PRESENTATION OF CASE: We treated four patients. Firstly, in cases 1 and 2,
      we introduced VAC therapy to the management of SSI of the perineal wound after
      APR, and it was useful to control postoperative perineal wound infection. And
      also, in cases 3 and 4, we introduced VAC therapy to prevent perineal wound
      infection. Perineal wound infection did not happen. DISCUSSION: A vertical rectus
      abdominis myocutaneous flap has been reported to decrease perineal wound
      complications including pelvic abscess and open perineal wound; however it
      results in significant operative blood loss, increased operative time, and
      additional surgical complications. In our cases, there were no complications
      relating to VAC therapy and it promoted rapid wound healing. Our results
      suggested that it is an effective treatment for APR in a high-risk case of an
      open perineal wound. CONCLUSION: VAC therapy is a less invasive method and a
      useful treatment for open perineal wound of APR.

PMID- 25942751
TI  - A rate adaptive control method for Improving the imaging speed of atomic force
      microscopy.
AB  - A simple rate adaptive control method is proposed to improve the imaging speed of
      the atomic force microscope (AFM) in the paper. Conventionally, the probe
      implemented on the AFM scans the sample surface at a constant rate, resulting in
      low time efficiency. Numerous attempts have been made to realize high-speed AFMs,
      while little efforts are put into changing the constant-rate scanning. Here we
      report a rate adaptive control method based on variable-rate scanning. The method
      automatically sets the imaging speed for the x scanner through the analysis of
      the tracking errors in the z direction at each scanning point, thus improving the
      dynamic tracking performance of the z scanner. The development and functioning of
      the rate adaptive method are demonstrated, as well as how the approach
      significantly achieves faster scans and a higher resolution AFM imaging. 

PMID- 25942752
TI  - Methods for topography artifacts compensation in scanning thermal microscopy.
AB  - Thermal conductivity contrast images in scanning thermal microscopy (SThM) are
      often distorted by artifacts related to local sample topography. This is
      pronounced on samples with sharp topographic features, on rough samples and while
      using larger probes, for example, Wollaston wire-based probes. The topography
      artifacts can be so high that they can even obscure local thermal conductivity
      variations influencing the measured signal. Three methods for numerically
      estimating and compensating for topographic artifacts are compared in this paper:
      a simple approach based on local sample geometry at the probe apex vicinity, a
      neural network analysis and 3D finite element modeling of the probe-sample
      interaction. A local topography and an estimated probe shape are used as source
      data for the calculation in all these techniques; the result is a map of false
      conductivity contrast signals generated only by sample topography. This map can
      be then used to remove the topography artifacts from measured data or to estimate
      the uncertainty of conductivity measurements using SThM. The accuracy of the
      results and the computational demands of the presented methods are discussed. 

PMID- 25942754
TI  - Mechanisms Underlying the Health Benefits of Plant Sterol and Stanol Ester
      Consumption.
AB  - The recent IMPROVE-IT trial clearly showed that lowering serum low-density
      lipoprotein cholesterol (LDL-C) concentrations via inhibiting intestinal
      cholesterol absorption through ezetimibe effectively lowered the number of new
      cardiovascular disease (CVD) events. This supports the use of other (dietary)
      interventions that lower serum LDL-C concentrations via comparable mechanisms
      such as described for plant sterol and stanol ester enriched functional foods.
      Therefore it is tempting to suggest that these compounds may have the same
      effects on CVD outcome, as described for ezetimibe in the IMPROVE-IT trial. This
      has however not been proven so far. A possible advantage of plant sterol and
      stanol ester enriched foods over ezetimibe-a typical single-target drug-is that
      these dietary compounds act on multiple targets, since they not only lower serum
      LDL-C concentrations, but also lower serum triacylglycerol (TAG) concentrations
      in subjects with elevated serum TAG concentrations. In addition, they might
      influence the functioning of our immune system via a changed activity of the
      regulatory T-cells. This combination of effects makes these compounds highly
      attractive to decrease CVD risk. 

PMID- 25942755
TI  -   Relevance of animal models for wound healing.
AB  - Animal models and in-vitro assays have become indispensable tools for
      researchers in nearly every scientific discipline. Although definitive studies,
      which are conducted on human subjects, are the final testimonial of product
      efficacy, such studies can present several practical, ethical, and moral
      concerns. In-vitro assays are extremely useful when examining the effect of
      agents on particular cell types or specific environmental factors that could be
      influential during repair or infection. Some of the attractive benefits of these
      studies include: 1) relatively inexpensive, 2) fast, 3) convenient, and 4)
      provide important information on their potential cell to cell function. However,
      in-vitro assays are incapable of completely reproducing biological conditions
      such as immune response, healing, and disease. Animal models are the next step
      when assessing product efficacy. Animal models are beneficial to wound research
      because of their compliance, and are ethical, easily manipulated, and flexible.
      Both small and animal large animal studies have their benefits and limitations.
      Pre-clinical testing should address toxicology, safety, and efficacy effects,
      preferable in a dose-response fashion. Ultimately well-controlled, randomized
      clinical trials are needed to finally demonstrate the true potential of any
      formulation. Overall, product development of wound healing/infection therapies is
      a progression of steps within each stage (in-vitro to in-vivo) and need to be
      carefully conducted to obtain an optimal product for the patient. 

PMID- 25942753
TI  - Nuclear bodies: the emerging biophysics of nucleoplasmic phases.
AB  - The cell nucleus contains a large number of membrane-less bodies that play
      important roles in the spatiotemporal regulation of gene expression. Recent work
      suggests that low complexity/disordered protein motifs and repetitive binding
      domains drive assembly of droplets of nuclear RNA/protein by promoting
      nucleoplasmic phase separation. Nucleation and maturation of these structures is
      regulated by, and may in turn affect, factors including post-translational
      modifications, protein concentration, transcriptional activity, and chromatin
      state. Here we present a concise review of these exciting recent advances, and
      discuss current and future challenges in understanding the assembly, regulation,
      and function of nuclear RNA/protein bodies. 

PMID- 25942756
TI  - Animal models of tissue ischemia to evaluate the importance of oxygen in the
      wound healing environment .
AB  - Localized tissue ischemia is a key factor in the development and poor prognosis
      of chronic wounds. The wide variety of wounds that occur in humans along with
      multiple comorbidities has precluded the ability to truly define, understand, and
      optimize treatment(s) for chronic wounds. As these difficult wounds appear to be
      uniquely human, investigators have had to create models of impaired wound healing
      for experimental manipulation. The ideal animal model would be relatively
      inexpensive, reproducible, and adaptable so that laboratories could use it to
      mimic the human condition. This article will review the current understanding of
      the effect of ischemia on wound healing and examine the features of currently
      available animal models that simulate ischemic wounds. 

PMID- 25942757
TI  -  Wound healing kinetics of the genetically diabetic mouse.
AB  - The increased number of chronic nonhealing wounds mirrors the epidemic of type 2
      diabetes. Diabetic animal models may allow for better understanding of the
      pathophysiology of wound healing and may lead to the pre-clinical testing of a
      variety of therapeutic modalities for this patient group. The authors present an
      overview of the literature on excisional wound mouse models and focus on the
      authors' experience with the db/db mouse. Excisional wounds in wild type mice
      heal quickly due primarily to wound contraction, which is delayed in the db/db
      mouse. In this animal model it is possible to study and quantify the main
      mechanisms of healing and produce highly reproducible information. Differences in
      methodologies, infection control, as well as fine details such as the dressing
      option, partially explain heterogeneous results in the literature. Given the
      increase of the diabetic population, the db/db mouse model provides a powerful
      tool to study the effects of therapeutics for improving wound healing. The
      standardization of this animal model represents an important aspect to improve in
      the wound care field. 

PMID- 25942758
TI  - Regulatory Aspects Related to Plant Sterol and Stanol Supplemented Foods.
AB  - This chapter reviews regulatory frameworks for plant sterol containing functional
      foods in various jurisdictions including Europe, North America, South America,
      Asia and, Australia/New Zealand. Included is a discussion on approval of plant
      sterols as novel food ingredients in some countries, as well as details on the
      type of health claims permitted in the marketing and sale of foods enriched with
      plant sterols within each jurisdiction. Based on the abundance of clinical trial
      data, many countries around the world have now approved the use of claims
      relating the cholesterol-lowering effect of plant sterols, further attesting to
      their value as functional food ingredients. 

PMID- 25942759
TI  - [Five star dentistry - IV Congress of European Federation for the Advancement of
      Anesthesia in Dentistry].
AB  - The Russian delegation of the European Federation for the Advancement of
      Anesthesia in Dentistry (EFAAD) participated in IV Congress of EFAAD where were
      considered such problems of dental and anxiolysis in patients with severe
      concomitant diseases and training dentists improvements on such problems as
      anesthesia, sedation, prophylaxis and emergency management inpatients with
      accompanying diseases.

PMID- 25942761
TI  - Foot problems.

PMID- 25942762
TI  - New oral anticoagulants  and perioperative  management of 
      anticoagulant/antiplatelet  agents.

PMID- 25942763
TI  - Dear editor.

PMID- 25942764
TI  - [Role of morphofunctional adrenal changes in pathogenesis of water-electrolyte
      disorders in patients with acute intestinal obstruction].

PMID- 25942765
TI  - [Institute of main surgeons of fleets (by the 70th anniversary of the victory in
      the Great Patriotic War)].

PMID- 25942766
TI  - [Olaf Breidbach (1957-2014)].

PMID- 25942767
TI  - [In Process Citation].
AB  - While the history of Soviet forensic psychiatry remains a subject of continuing
      interest in the ,,politics of remembrance," there is a conspicuous dearth of
      historiographic studies in this area. Drawing on newly accessible source
      material, this study addresses this gap in the literature, delineating issues of
      key concern to the topic. The paper first explores specific interrelationships
      between legal and nosological points of view in the theories of forensic
      psychiatry that prevailed in the USSR. On this basis, it then reconstructs the
      functional characteristics of the "diagnosis factory" run under the auspices of
      Andrej V. Sneshnewski, illuminating the role of this school of psychiatry in the
      context of the history of medicine. In the third section of the paper, the
      discussion turns to institutional conditions, political factors, ideological
      implications, and socio-cultural contexts related to how hegemonic actors in
      Soviet forensic psychiatry dealt with non-conformers. In this context, a focus is
      placed on instances of resistance and dissidence within Soviet psychiatry. In
      particular, the paper discusses how polemics that relied on values and norms were
      of central importance to the political misuse of psychiatry as a nucleus and
      catalyst of democratic self-reflection during the reform era that took place
      under Mikhail Gorbachev.

PMID- 25942768
TI  - [In Process Citation].
AB  - A discrepancy of word choice can be noted in the account of Jacob's wrestling at
      the river Jabbok (Gen. 32, 23-33) if we compare the Hebrew version on one hand
      and the Greek and Latin versions on the other. The lesion that incurred Jacob a
      permanent limp and constitutes the dietary ban on the sciatic nerve is described
      as a luxation or strain (see symbol) of the hip joint (see symbol) in the Hebrew
      bible, whereas Septuagint, Vetus Latina and Vulgata use (see symbol) and emarceo
      or obstipesco as well as (see symbol) and latitudinem faemoris. They thus suggest
      hints of a painful sensory deficit felt on the outside of the thigh and a
      paralysis. In a synopsis of knowledge of sciatica in antiquity and modern
      knowledge on nerve root irritation and compression syndromes, it can be argued
      that the originators of the Septuagint and subsequent Greek and Latin translators
      and authors supported their translations with a diagnosis that we today would
      call an L5-syndrome with sciatica, sensory deficit, weak foot dorsiflexion and
      Trendelenburg gait.

PMID- 25942769
TI  - [In Process Citation].
AB  - Since the middle of the Nineteenth Century, neurophysiological researchers such
      as Theodor Fechner (1801-1887), Wilhelm Wundt (1832-1920), or Maximilian Ruppert
      Franz von Frey (1852-1932) started to analyze the causes, propagation, and
      perception of "pain" in the nervous system through the systematic use of
      experimental laboratory investigations. Particularly, Theodor Fechner's
      groundbreaking works made the contemporary neurophysiologists aware of the
      potential inclusion of psychological and subjective perceptions as a respectable
      object for the experimental study in mid-nineteenth century laboratories and
      clinical wards. Wilhelm Wundt frequently crossed the intersections between animal
      and human subject research and opened up many theoretical discussions, which also
      incorporated pluridisciplinary perspectives. On the research side, Wundt worked
      with many experimental physiological methods, developed theoretical
      psychophysiological considerations, and provided a detailed philosophical
      analysis of the new experimental findings and the subjective accounts of pain
      perceptions in his test persons--among many other experimental and investigative
      approaches. While each one of these neurophysiologists' research programs have
      been extensively studied in their own right, their mutual contributions to modern
      pain research and impact on this emerging interdisciplinary field of biomedical,
      psychophysiological and philosophical studies have so far not sufficiently been
      analyzed from a historiographical perspective. This even regards their highly
      sophisticated instruments and apparatuses that they applied to the study of pain,
      which Maximilian von Frey used further in the medical wards at the Fin de Siecle.
      These instruments became applied to many patients with acute or chronic pain
      disorders. In a way, the substantial time lag between early laboratory research
      and the application of these findings in the medical clinics of the time could
      also be explained as a process of newly defining the boundaries of the
      experimental instrumentation by situating the physiological apparatuses and
      experiments alongside the spectrum from threshold values to normal values. This
      hence led to the recalibration of the new field of investigations of pain
      phenomena. Until today, the elements of phenomenological "identification",
      "evaluation" and "physical reduction", which these pioneers had started and
      importantly put on the scientific map of nineteenth-century medicine and
      neuroscience, accompany the scientific endeavour of modern pain research.

PMID- 25942770
TI  - Brain ventricle diagrams: a century after Walther Sudhoff new manuscript sources
      from the XVth century.

PMID- 25942771
TI  - [In Process Citation].
AB  - We report on a newly discovered letter by Christoph Rothmann, dated July 1st
      1584, and addressed to Johann Ernst of Anhalt. The letter supports the earlier
      assumption that Johann Ernst recommended Rothmann to Landgrave Wilhelm of Hesse,
      as Rothmann asks for Johann Ernst's help on the matter in this new source. More
      importantly Rothmann refers to his attempts to make Copernicus' calculations
      compatible with the Ptolomean model, which demonstrates that already at this
      stage of his career he was working on such a compromise, and not only after being
      influenced by Raimarus Ursus or Tycho Brahe, as has been argued by some authors.

PMID- 25942772
TI  - Humans and uniqueness.
AB  - A defining force in the shaping of human identity is a person's need to feel
      special and different from others. Psychologists term this motivation Need for
      Uniqueness (NfU). There are manifold ways to establish feelings of uniqueness,
      e.g., by showing unusual consumption behaviour or by not conforming to majority
      views. The NfU can be seen as a stable personality trait, that is, individuals
      differ in their dispositional need to feel unique. The NfU is also influenced by
      situational factors and social environments. The cultural context is one
      important social setting shaping the NfU. This article aims to illuminate the NfU
      from a social psychological perspective.

PMID- 25942773
TI  - "Vibrational bonding": a new type of chemical bond is discovered.
AB  - A long-sought but elusive new type of chemical bond, occurring on a minimum-free,
      purely repulsive potential energy surface, has recently been convincingly shown
      to be possible on the basis of high-level quantum-chemical calculations. This
      type of bond, termed a vibrational bond, forms because the total energy,
      including the dynamical energy of the nuclei, is lower than the total energy of
      the dissociated products, including their vibrational zero-point energy. For this
      to be the case, the ZPE of the product molecule must be very high, which is
      ensured by replacing a conventional hydrogen atom with its light isotope muonium
      (Mu, mass = 1/9 u) in the system Br-H-Br, a natural transition state in the
      reaction between Br and HBr. A paramagnetic species observed in the reaction Mu
      +Br2 has been proposed as a first experimental sighting of this species, but
      definitive identification remains challenging.

PMID- 25942775
TI  - Sustainable nanotechnology.

PMID- 25942774
TI  - Advances in antihydrogen physics.
AB  - The creation of cold antihydrogen atoms by the controlled combination of
      positrons and antiprotons has opened up a new window on fundamental physics. More
      recently, techniques have been developed that allow some antihydrogen atoms to be
      created at low enough kinetic energies that they can be held inside magnetic
      minimum neutral atom traps. With confinement times of many minutes possible, it
      has become feasible to perform experiments to probe the properties of the
      antiatom for the first time. We review the experimental progress in this area,
      outline some of the motivation for studying basic aspects of antimatter physics
      and provide an outlook of where we might expect this field to go in the coming
      years.

PMID- 25942776
TI  - Fossil fuel use is limited by climate, if not by resources, and "peak soil"..

PMID- 25942779
TI  - Search is on for primary care providers.

PMID- 25942780
TI  - Health plans deploy new systems to control use of lab tests.

PMID- 25942781
TI  - Accolade's expanding clientele likes its emphasis on members.

PMID- 25942783
TI  - A conversation with Mark W. Friedberg, MD. Medical homes haven't proven
      themselves--yet.

PMID- 25942784
TI  - Many clinical studies may not be dependable.

PMID- 25942785
TI  - Formulary decisions without comparative effectiveness research.

PMID- 25942786
TI  - Specialty meds will put pressure on overall costs.

PMID- 25942787
TI  - You can get there from here with these new mobility aids.

PMID- 25942788
TI  - Plunging rate of elective preterm deliveries is something all stakeholders can
      celebrate.

PMID- 25942789
TI  - DNA-based stool-sample test might improve colorectal cancer screening.

PMID- 25942790
TI  - Engagement and advocacy.

PMID- 25942791
TI  - Cholecystocolonic fistula.
AB  - Cholecystoenteric fistulas are a complication of biliary disease, having an
      estimated incidence in the range of 0.1 - 0.5 percent. Roughly 8-27 percent of
      these are of the cholecystocolonic type,1 occurring most commonly at the hepatic
      flexure. An 82-year-old male presented to our tertiary hospital emergency
      department and was diagnosed with a cholecystocolonic fistula (CCF) by CT
      imaging. Surgical evaluation confirmed the CT diagnosis with subsequent removal
      of the fistula and gallbladder, which was curative.

PMID- 25942792
TI  - The hill battles of Khe Sanh: a marine corps doctor remembers.

PMID- 25942793
TI  - Katherine L. Esterly, MD.

PMID- 25942794
TI  - [Intravenous adenosine and radiopharmaceutical injection in the same line was
      feasible in adenosine stress myocardial perfusion. imaging].
AB  - Adenosine stress myocardial perfusion imaging was performed with an intravenous
      adenosine and radiopharmaceutical injection in the same line. A syringe
      containing 720 MUg/kg of adenosine in 40 ml of saline was prepared and injected
      at the constant infusion rate of 400 ml/h. Adenosine was temporarily stopped by
      the stopcock when 1.5 ml of thallium was injected for 0.5 second from the three
      way stopcock with two ways opened. Thereafter, the stopcock was returned to the
      original position in 0.5 second, and adenosine flow returned to the constant flow
      rate again. In this method, 0.75% of adenosine total dose was injected at a rate
      of 3.0 ml/s and adenosine was stopped for 3.6 second. There were no significant
      differences in either effects and adverse events of adenosine between this method
      and two intravenous injection line method. Adenosine stress in one venous line
      method would be an easy method maintaining the dose effect and safety.

PMID- 25942795
TI  - [Pixel values of [15O]H2O2 PET images with OSEM algorithm depending on numbers of
      subset and iteration times: comparative assessment to FBP].
AB  - To investigate a potential application of ordered subsets expectation
      maximization (OSEM) algorithm for clinical [15O]H2O PET studies, region of
      interest (ROI) measurements were performed on both images with OSEM and filtered
      back projection (FBP). Forty OSEM images were reconstructed with variable
      combinations of numbers of the subset (1-40) and iteration times (2-12). PET
      scans were acquired using a PET/CT scanner (Discovery ST Elite, GE), and 3T-MRI
      images were obtained for fusion images. The mean values were measured on the
      frontal cortical regions in the middle cerebral artery distribution. Differences
      of the values between the OSEM and FBP were evaluated as %Error. Relationship
      between ROI mean values and the iteration times was investigated on the OSEM
      images. The smallest %Error 0.4% was measured in the combination of the subset
      number 10 and iteration times 8 [10, 8], and in that of [28, 2].The mean values
      were stable with iteration number 8 or more. OSEM image with [28, 2] was
      reconstructed in a shorter time (2.5 min) than that with [10, 8] (6 min). OSEM
      image with [28, 2] was superior to that with [10, 8] in the qualitative
      evaluation. The mean values on OSEM images with [28, 2] were comparable with
      those on FBP images with little artifacts and higher spatial resolution. OSEM
      with optimal parameter setting seemed applicable for both quantitative and
      qualitative [15O]H2O PET studies.

PMID- 25942796
TI  - [Assessment of validity of the archived standard curve in endotoxin assay,
      produced in other facilities].
AB  - We have reported the possibility of the use of the archived standard curve of
      endotoxin assay, which is prepared in the same facility from the viewpoint of the
      accuracy and precision. In this study, the possibility of the use of the archived
      standard curves prepared in the different facilities was investigated with the
      same data set in the previous paper. The evaluation was performed with the
      recovery rate of the concentrations of the standard solutions, as the same method
      as the previous study. The clotting times of the standard solutions were
      substituted into the standard curves prepared in the different facilities from
      those, in which standard solutions were prepared. The recovery rates were 86.1
      125.0%, and the range was almost the same as that when the facility preparing
      standard solutions were the same as that preparing the standard curve. From this
      data, if the protocols of the preparation of standard solutions, such as mixing
      and the interval timing until set to the apparatus and so on, can be set the same
      between the endotoxin test and the preparation of the archived standard curves,
      the endotoxin concentration calculated with the archived standard curves prepared
      in other facilities were not varied very much, compared to the true values and
      the values obtained from the use of the archived standard curves prepared in the
      same facility.

PMID- 25942797
TI  - Fabrication of nanogels for delivery of molecules.
AB  - Recently, nanogels have been extensively studied as a means to deliver bioactive
      molecules such as drugs, proteins, and vaccines due to their versatile and unique
      properties such as high water absorption, easy production, surface modification,
      high stability and biocompatibility. Various materials including natural
      polymers, synthetic polymers, peptides, and proteins have been selected for
      fabrication of nanogels to achieve a targeted, sustained, or protected delivery
      depending on biomedical applications and bioactive molecules. This review
      describes a variety of nanogel fabrication for applications in molecular delivery
      systems. The detail of materials and approaches for preparation of nanogels will
      be discussed, including free radical polymerization, controlled/living radical
      polymerization, self-assembly, and metal/nanogel composites.

PMID- 25942798
TI  - Nanotechnology for diagnosis and treatment of infectious diseases.
AB  - The emergence of co-infections and the evolution of drug-resistant pathogens
      limit the utility of current therapies against infections, and developing
      countries in particular are facing a great challenge in combating infectious
      disease. Moreover, any failure to control the spread of infectious diseases would
      also represent a threat to developed countries. Recent developments in
      nanotechnology allow us to address this issue at two levels: diagnostics and
      treatment. Prevention of the spread of infectious pathogens requires rapid and
      accurate identification of the infectious agents for proper treatment. Recently
      developed fluorescent nanoparticles are so sensitive that even a single
      nanoparticle is capable of emitting a strong enough signal to be captured, thus
      enabling early identification of infections. Proper and effective treatment not
      only saves the patient, but also prevents the spread of the pathogens. Specific
      nanoparticle vehicles developed to encapsulate therapeutic agents and deliver
      them to a target site represent a promising strategy to boost immune responses
      for vaccination and boost the efficacy of drugs for treatment. Here, we describe
      a variety of nanotechnologies for use in applications such as immune response
      modulation, drug delivery, diagnostics, and treatment, which are especially
      needed in developing countries.

PMID- 25942800
TI  - Enhanced loading efficiency and sustained release of doxorubicin from hyaluronic
      acid/graphene oxide composite hydrogels by a mussel-inspired catecholamine.
AB  - Hydrogels have been widely investigated as depots and carriers for drug delivery.
      For example, hydrogels have been successfully used to encapsulate a variety of
      pharmaceuticals, such as peptides and proteins. Recently, carbon
      material/hydrogel hybrid systems have been of interest as new hydrogel systems
      because of the attractiveness of structural reinforcement for biomedical
      applications. In particular, graphene and graphene oxide (GO) have been
      recognized as novel biomaterials with unique physical, electrical, and thermal
      properties. Among the various applications of these materials, many research
      groups are intensively exploring the biomedical applications of graphene and GO.
      In this study, we propose a new role for GO in hybrid hydrogels, with the
      inclusion of GO in the gel network resulting in a nearly 90% enhancement in the
      loading of small, hydrophobic drugs (e.g., doxorubicin, Dox) compared to the
      hydrogel without encapsulated GO. The hydrogels were prepared from hyaluronic
      acid (HA), with a mussel-inspired crosslinking chemistry used to prepare the HA
      hydrogels. Dox was then loaded into the hydrogels. The HA/GO composite hydrogel
      not only enhanced the loading amount but also exhibited long-lasting anticancer
      activity over 10 days. We believe that these graphene oxide-containing composite
      hydrogels can solve one of the challenges in the application of hydrogels by
      improving the loading efficiency of small-molecule drugs.

PMID- 25942799
TI  - Hyaluronic acid-siRNA conjugate/reducible polyethylenimine complexes for targeted
      siRNA delivery.
AB  - The clinical applications of therapeutic siRNA remain as a challenge due to the
      lack of efficient delivery system. In the present study, hyaluronic acid-siRNA
      conjugate (HA-SS-siRNA)/reducible polyethylenimine (BPEI1.2k-SS) complexes were
      developed to efficiently deliver the siRNA to HA receptor abundant region with
      the improved siRNA stability. HA and siRNA were conjugated with disulfide bonds,
      which are cleavable in cytoplasm. The synthesized HA-SS-siRNA was further
      complexed with BPEI1.2k-SS, resulting in the formation of spherical
      nanostructures with approximately 190 nm of size and neutral surface charge. HA
      SS-siRNA/BPEI1.2k-SS complexes exhibited the improved stability against serum
      proteins or polyanions. These complexes were successfully translocated into
      intracellular region via HA receptor-mediated endocytosis, and silenced target
      gene expression.

PMID- 25942801
TI  - Selectively micro-patterned fibronectin for regulating fate of human mesenchymal
      stem cell.
AB  - Microenvironment of the extracellular matrix can influence cellular responses
      through alternation of initial attachment and induce production of new tissue. To
      study the effect of such microenvironment on the relationship of cell
      cytoskeletal shape and its biological behaviors such as adhesion, proliferation
      and differentiation, we designed a patterned strip line of fibronectin on self
      assembled monolayers via microcontact printing. The physiological behavior of
      human mesenchymal stem cell (hMSC) on defined micro-patterns of fibronectin was
      evaluated after 4 h and 2 days of culture. Initial adhesion of hMSCs on a
      substrate with pattern spacing of 11 MUm was stabilized faster than that on other
      substrates. Ratio of proliferating hMSC on 5 and 11 MUm substrate constantly
      maintained a high rate. hMSCs on 5 and 11 MUm substrate could adhere to substrate
      as spreading from fibronectin pattern line to several and lateral fibronectin
      pattern line. Their nucleus area could represent artificial increase by widely
      spreading on several fibronectin pattern lines. On the contrary to this, ratio of
      proliferating hMSC on 20 MUm substrate constantly maintained a low rate less than
      even control and 0 MUm substrate without fibronectin pattern. Tiny nucleus caused
      narrow and elongated hMSC morphology on 20 MUm substrate gave the negative effect
      on the cell adhesion and proliferation. However, hMSCs on 20 MUm substrate
      possessed not only slightly increased value of GO/G1 phase but also down
      regulation of CD marker expression compared with other groups. These results show
      initial adhesion and morphology of hMSC could regulate specific cellular behavior
      of hMSC.

PMID- 25942802
TI  - Effects of cyclic impacts on the performance of a piezo-composite electricity
      generating element in a d33 mode energy harvesting.
AB  - The increasing use of piezoelectric generators to harvest energy from various
      ambient sources requires the establishment of durability data for piezoelectric
      materials. In this paper, a d3 mode piezocomposite electricity generating element
      (PCGE) was tested for its durability under cyclic impact loading. For this
      purpose, a motor driven lever system was designed to apply constant impact force
      on PCGEs. To investigate the durability of PCGEs, the output voltage of the PCGEs
      was observed upon repeated application of an impact force until eventual loss of
      the generated voltage. The experimental results enabled to determine the number
      of cycles until which PCGEs can be used without loss of their electricity
      generation performance with respect to the stress level applied on the PCGEs. At
      low stress level (around 0.76 MPa or lower), the PCGE showed almost insignificant
      degradation even after 2 million cycles whereas degradation occurred sooner
      (after 8 x 10(5) cycles) at higher stress levels (around 0.92 MPa or higher). The
      effects of impact loading on the durability of the PCGEs were also examined by X
      ray photographs of the specimens.

PMID- 25942803
TI  - Structural design of microfluidic channels for blood plasma separation.
AB  - Microfluidics devices for separation of plasma from whole blood can be applied to
      numerous clinical laboratory and point-of-care diagnostics, since over 90% of
      blood diagnosis tests are conducted using plasma. This paper proposed a
      structural design of microfluidic channels for blood plasma separation. The Euler
      Euler Laminar Flow Model in COMSOL Multiphysics has been utilized to simulate the
      blood flow behavior in microchannels. Micro chips with separating microchannels
      of different designs were fabricated and tested. The geometrical effect of
      microchannels on plasma separation was investigated. Simulation results show that
      curved channel contributes little in lateral migration of cells in low flow rate
      and becomes a difficult choice in the case of high flow rate due to the coupling
      of centrifugal migration and Dean Vortex. Studies on the bifurcation corner
      radius and the angle between main channel and side channel show that an abrupt
      change in flow direction of cell free layer helps to get more plasma with higher
      purity. An optimal design of multi-bifurcation separator has been achieved by
      balancing the flow resistances of the side channels and the main channels.

PMID- 25942804
TI  - Low-cost design and fabrication of an anthropomorphic robotic hand.
AB  - Human hand signifies a magnificent and challenging example for scientists and
      engineers trying to replicate its complex structure and functionality. This paper
      proposes a bio-mechatronic approach for the design of an anthropomorphic
      artificial hand capable of performing basic human hand motions with fundamental
      gripping functionality. The dexterity of the artificial hand is exhibited by
      imitating the natural motion of the human fingers. Imitation is produced
      according to the data acquired from the flex sensors attached to the human
      fingers. In order to have proper gripping, closed-loop control is implemented
      using the tactile sensors. Feedback for the closed-loop control is provided by
      force sensing resistors (FSRs), attached on the fingertips of the robotic hand.
      These sensors also enable handling of fragile objects. The mathematical model is
      derived using forward kinematics and also simulated on MATLAB to ascertain the
      position of robotic fingers in 3D space.

PMID- 25942805
TI  - Transient analysis of biocomposite laminates with delamination.
AB  - The transient analysis of smart biocomposite laminates with delamination at ply
      interfaces is investigated, by using an electro-mechanical coupled improved
      layerwise theory. The piezoelectric coupling effect was modeled using higher
      order electric potential. Four-node plate elements were used for finite element
      implementation. Linear Lagrange interpolation functions were used for in-plane
      structural unknowns and electric unknowns, and a Hermite cubic interpolation
      function was used for out-of-plane structural unknowns. Single delamination was
      seeded in the biocomposite laminates at three different locations, to study the
      effects of delamination. Numerical results were obtained by using the Newmark
      beta algorithm. The results showed that the time history of nodal displacement
      and sensor output didn't give enough information of delamination. However, the
      power spectral density of the time history provided clear information of the
      delamination effects. From the results, it is expected that the proposed theory
      has the potential to predict the dynamic characteristics and delamination effects
      in smart biocomposite laminates.

PMID- 25942806
TI  - Dissipation factor of acrylic dielectric elastomer--an experimental study.
AB  - This paper studies the effects of frequency, pre-strain and electrode types on
      the dielectric property of a commercially available and most widely used acrylic
      elastomer, VHB 4910. The acrylic VHB film is pre-stretched in biaxial directions
      with the help of an in-house developed biaxial stretching device. The stretched
      film has been sandwiched between two card board frames to prepare samples of
      different pre-stretch values. Three different types of electrodes namely copper
      tape, silver grease and carbon grease have been pasted on the both sides of
      prestretched samples. Dissipation factor of pre-stretched and electrode adhered
      VHB sample has been experimentally determined at different frequency (upto 1 MHz)
      of input voltage using a LCR meter. Experimental results on the variation of
      dissipation factor with pre-straining, frequency (low to high) and electrode
      types are reported. The dissipation factor value is further used to estimate
      electrical efficiency at different biaxial pre-straining, frequency and electrode
      types.

PMID- 25942807
TI  - Fabrication and characteristics of a multilayered ionic polymer metal composite
      based on Nafion/tetraethyl orthosilicate and Nafion/MCNT nanocomposites.
AB  - Nafion/multi-walled carbon nanotubes (Nafion/MCNT) and Nafion/tetraethyl
      orthosilicate (Nafion/TEOS) nanocomposites were prepared and used as starting
      materials in the fabrication of an ionic polymer metal composite (IPMC).
      Experimental data show that the Nafion/MCNT-based IPMC exhibited a blocking force
      that is two times higher than that of bare Nafion-based IPMC. This higher
      blocking force is due to the stable homogeneous dispersions of multiwalled carbon
      nanotubes as well as to their improved conductivity. Meanwhile, the Nafion/TEOS
      based IPMC generated a blocking force that is more than two times higher than
      that of bare Nafion-based IPMC because of the induced channels and increased
      water content. In this paper, a novel Nafion membrane containing a primary
      Nafion/TEOS layer sandwiched between two outer Nafion/MCNT nanocomposite layers
      was prepared by consecutive casting of liquid solutions. By using the
      multilayered Nafion membrane, IPMC was carefully fabricated by electroless
      plating. In addition, the blocking force, displacement, and electric current of
      the IPMC were measured on the test apparatus. The multilayered IPMC exhibited a
      significantly improved blocking force of 6.5 gf as well as a long effective air
      operating life time. Finally, this multilayered IPMC was successfully used to
      actuate the robotic fish.

PMID- 25942809
TI  - Possibility of cellulose-based electro-active paper energy scavenging transducer.
AB  - In this paper, a cellulose-based Electro-Active Paper (EAPap) energy scavenging
      transducer is presented. Cellulose is proven as a smart material, and exhibits
      piezoelectric effect. Specimens were prepared by coating gold electrodes on both
      sides of cellulose film. The fabricated specimens were tested by a base excited
      aluminum cantilever beam at resonant frequency. Different tests were performed
      with single and multiple parallel connected electrodes coated on the cellulose
      film. A maximum of 131 mV output voltage was measured, when three electrodes were
      connected in parallel. It was observed that voltage output increases
      significantly with the area of electrodes. From these results, it can be
      concluded that the piezoelectricity of cellulose-based EAPap can be used in
      energy transduction application.

PMID- 25942808
TI  - Free-edge stress analysis of functionally graded material layered biocomposite
      laminates.
AB  - A stress function based theory is proposed to obtain free-edge stress
      distributions for three-dimensional, orthotropic, linearly elastic rectangular
      biocomposite laminates with surface-bonded functionally graded materials (FGM).
      The assumed stress fields automatically satisfy the pointwise equilibrium
      equation, as well as traction-free and free edge boundary conditions. The
      complementary virtual work principle, followed by the general eigenvalue solution
      procedure, is used to obtain 3-D free edge stress states. A typical stacking
      sequence of composite laminate is used as numerical investigation with surface
      bonded FGMs. It is shown that with proper exponential factor of FGMs, the
      interlaminar stresses at the FGM layer interface can be reduced significantly, in
      return to prevent debonding of FGM layers. This approach can be useful in the
      design of functionally graded material layered biocomposite structures.

PMID- 25942810
TI  - Bio-inspired bending actuator for controlling conical nose shape using
      piezoelectric patches.
AB  - In this paper, a bio-inspired bending actuator was designed and fabricated using
      piezoelectric patches and cantilever-shaped beam for controlling nose shape. The
      aim of this study is to investigate the use of the bending actuator. PZT and
      single crystal PMN-PT actuators were used to generate translational strain and
      shear stress. The piezoelectric patches were attached on the clamped cantilever
      beam to convert their translational strains to bending motion of the beam. First,
      finite element analysis was performed to identify and to make an accurate
      estimate of the feasibility on the bending actuation by applying various voltages
      and frequencies. Based on the results of the FEM analysis, the experiments were
      also performed. Static voltages and dynamic voltages with various frequencies
      were applied to the bending actuators with PZTs and PMN-PTs, and the rotation
      angles of the nose connected to the top of bending actuators were measured,
      respectively. As the results, the bending actuator using PMN-PT patches showed
      better performances in all cases. With the increases of signal frequency and
      input voltage, the rotation angle also found to be increased. Especially at the
      frequency of 5 Hz and input voltage of 600 V, the nose generated the maximum
      rotation angle of 3.15 degree.

PMID- 25942811
TI  - Discrete element method for emergency flow of pedestrian in S-type corridor.
AB  - Pedestrian flow in curved corridor should be modeled before design because this
      type of corridor can be most dangerous part during emergency evacuation. In this
      study, this flow is analyzed by Discrete Element Method with psychological
      effects. As the turning slope of corridor increases, the evacuation time is
      linearly increases. However, in the view of crashed death accident, the case with
      90 degree turning slope can be dangerous because there are 3 dangerous points. To
      solve this matter, the pedestrian gathering together in curved part should be
      dispersed.

PMID- 25942812
TI  - Mechanical behavior of polycarbonate fabricated at different cooling speeds.
AB  - This comparative study investigates the mechanical properties of polycarbonate in
      manufacturing conditions of different cooling speed. All experiments were
      conducted using 0.8 mm thick specimens made of commercial Polycarbonate granule
      (3 mm), according to the ASTM standard. The test results illustrate that
      polycarbonate specimens manufactured in fast-cooling (FC) condition exhibit at
      least five times higher resilience in ambient temperature than those of slow
      cooling (SC) condition. However, the resilience of FC polycarbonate specimen
      quickly deteriorates, as the test temperature reduces to negative 40 degrees C.
      On the other hand, SC specimens barely changed their tensile properties. Thus,
      the test reveals that tensile properties of polycarbonate are significantly
      affected by the cooling speed in the manufacturing stage, and exposed temperature
      conditions. In this manuscript, the correlations between toughness and yield
      strength of polycarbonate specimen are summarized and discussed in terms of the
      cooling conditions and environmental temperature.

PMID- 25942813
TI  - Bio-lnspired dielectric elastomer actuator with AgNWs coated on carbon black
      electrode.
AB  - Bio-inspired dielectric elastomer actuators with AgNW-coated carbon black
      electrodes were developed in this study. The novel elastomer actuators show large
      in-plane deformations by electrical stimulation through the both electrodes. When
      a certain input voltage is applied to the elastomer electrode, the electrostatic
      force between cathode and anode electrodes compress the dielectric elastomer
      film, resulting large in in-plane direction deformation. The expanded area of the
      circular actuation device under 70 mV/m electric field was measured up to 50% due
      to a synergistic effect of highly conductive AgNW network and ultrahigh
      capacitance of carbon black electrodes.

PMID- 25942814
TI  - Chitosan/polyurethane blended fiber sheets containing silver sulfadiazine for use
      as an antimicrobial wound dressing.
AB  - Electrospun chitosan (CTS) nanofibers have been well known for use as a wound
      dressing in the biomedical field. Nevertheless, fatal bacterial infections are
      still a serious problem when CTS nanofibers are used for wound treatment. In this
      study, we designed a novel wound dressing based on blending the chitosan with
      polyurethane (CTS/PU) containing silver sulfadiazine (AgSD) in order to enhance
      both antibacterial activity and mechanical strength. This fiber sheet was
      produced using the electrospinning (ELSP) technique. The CTS/PU containing AgSD
      fiber sheet was characterized by energy-dispersive X-ray spectroscopy (EDX). The
      physicochemical properties of the CTS/PU/AgSD fiber sheets were also
      characterized by thermogravimetric analysis (TGA) and Fourier transform infrared
      spectroscopy (FT-IR). The electrospun fibers were morphologically characterized
      by scanning electron microscopy (SEM) and transmission electron microscopy (TEM).
      For an in vitro evaluation, the CTS/PU/AgSD fiber sheets were tested for their
      antibacterial activity against gram-negative Pseudomonas aeruginosa (P.
      aeruginosa), gram-positive Staphylococcus aureus (S. aureus) and Methicillin
      resistant Staphylococcus aureus (MRSA). The results indicate that CTS/PU/AgSD
      fiber sheets have strong antimicrobial activity as displayed by inhibition of
      bacterial growth and prevention of infection during the healing process. These
      results indicate that this material would be good for use as a wound dressing
      material.

PMID- 25942816
TI  - Comparison between organic sensitizers containing stilbene and azo group as
      bridging unit for dye sensitized solar cells.
AB  - While azo dyes have been widely used in dye industry, the azo dyes have been
      seldom applied as sensitizers to dye sensitized solar cells. In this study, new
      metal-free organic sensitizers, ST and AZ, which are same structures except
      bridging units, were synthesized and evaluated. ST containing stilbene as
      bridging unit gave higher energy conversion efficiency than AZ containing azo
      group as bridging unit. As a result of density functional theory (DFT)
      calculations, ST displayed more localized frontier molecular orbitals at lowest
      unoccupied molecular orbital (LUMO) states than AZ.

PMID- 25942815
TI  - Cellulose-silica/gold nanomaterials for electronic applications.
AB  - Cellulose and one dimensional nano-material composite has been investigated for
      various industrial applications due to their optical, mechanical and electrical
      properties. In present investigation, cellulose/silica and silica-gold hybrid
      biomaterials were prepared by sol-gel covalent cross-linking process. The
      tetraethoxysiliane (TEOS) and gold precursors and gamma
      aminopropyltriethoxysilane (gamma-APTES) as coupling agent were used for sol-gel
      cross-linking process. The chemical and morphological properties of
      cellulose/silica and cellulose/silica-gold nano-materials via covalent cross
      linking hybrids were confirmed by FTIR, XRD, SEM, and TEM analysis. In the sol
      gel process, the inorganic particles were dispersed in the cellulose host matrix
      at the nanometer scale, bonding to the cellulose through the covalent bonds.

PMID- 25942817
TI  - Damage analysis of biocomposite laminates using model order reduction.
AB  - The transient quasi-static Ritz vector method (TQSRV) is applied to efficiently
      calculate the transient response of a delaminated biocomposite laminate.
      Delamination of the laminated biocomposite structure was modeled using an
      improved layerwise displacement field. The piezoelectric coupling effect was
      modeled using higher order electric potential. One piezoelectric actuator was
      used to excite the laminated biocomposite plate, and one piezoelectric sensor was
      used to detect the transient structural response of the plate. Single discrete
      delamination was seeded in the laminated biocomposite plate, to investigate the
      effect of delamination. Three different locations of delamination through the
      thickness direction were considered, to study the effects of delamination on
      structural response. The Newmark-beta algorithm and the model order reduction
      (MOR) method were used, to obtain transient response of the delaminated composite
      plate under impulse loading. The effects of delamination were clearly observed in
      the power spectral density of the piezoelectric sensor output. From the results,
      it is concluded that the MOR is a very efficient method in predicting the damage
      effects of delaminated biocomposite structures.

PMID- 25942818
TI  - Preparation and characterization of chlorine doped Li3V2(PO4)3 as high rate
      cathode active material for lithium secondary batteries.
AB  - Monoclinic Li3V2(PO4)2.99Cl0.01 was synthesized using the conventional solid
      state method and the X-ray diffraction pattern was indexed based on P2(1)/n space
      group. The sharp cyclic voltammetric curves clearly revealed three lithium
      extraction/insertion processes at approximately 3.64, 3.72, 4.13, and 4.58 V
      during the anodic scan and 3.96, 3.58, and 3.48 V during the cathodic scan.
      Charge/discharge studies showed reduced electrolyte decomposition contribution in
      the case of the chlorine doped Li3V2(PO4)2.99Cl0.01 sample with an initial
      capacity of 176 mA h g(-1) at a 0.1 C current rate. The chlorine doped
      Li3V2(PO4)3 sample showed an increased capacity retention with an increase in
      current rate, even at a very high C-rate (20 C), than the pristine and carbon
      coated samples. The pristine and carbon coated Li3V2(PO4)3 samples showed a lower
      capacity retention of 71% and 84%, respectively, at a current rate of 0.1 C. In
      contrast, the chlorine doped Li3V,(PO4)3 sample retained 87% of the initial
      capacity (176 mA h g(-1)) at the same current rate but with a higher coulombic
      efficiency of 91%. The enhanced capacity retention for the chlorine doped
      Li3V2(PO4)3 was attributed to the reduction in polarization and decreased charge
      transfer resistance of the electrode.

PMID- 25942819
TI  - Nanometer-scale displacement measurement with high resolution using dual cavity
      Fabry-Perot interferometer for biomimetic robots.
AB  - A sensor of a biomimetic robot has to measure very small environmental changes
      such as, nanometer scale strains or displacements. Fiber optic sensor can be also
      one of candidates for the biomimetic sensor because the sensor is like thread and
      the shape of the sensor is similar to muscle fiber. A fiber optic interferometer,
      which is an optical-based sensor, can measure displacement precisely, so such
      device has been widely studied for the measurement of displacement on a nanometer
      scale. Especially, a Quadrature Phase-Shifted Fiber Fabry-Perot interferometer
      (QPS-FFPI) uses phase-information for this measurement, allowing it to provide a
      precision result with high resolution. In theory, the QPS-FFPI generates two
      sinusoidal signals of which the phase difference should be 90 degrees for the
      exact measurement of the displacement. In order to guarantee the condition of the
      phase difference, the relative adjustment of the cavities of the optical fibers
      is required. However, with such precise adjustment it is very hard to fix the
      proper difference of the two cavities for quadrature-phase-shifting. In this
      paper, a dual-cavity FFPI is newly proposed to measure the displacement on a
      nanometer-scale with a specific type of signal processing. In the signal
      processing, a novel phase-compensation algorithm is applied to force the phase
      difference to be exactly 90 degrees without any physical adjustment. As a result,
      the paper shows that the phase-compensated dual-cavity FFPI can effectively
      measure nanometer-scale displacement with high resolution under dynamic
      conditions.

PMID- 25942820
TI  - Active vibration control of ring-stiffened cylindrical shell structure using
      macro fiber composite actuators.
AB  - Vibration control performance of the ring-stiffened cylindrical shell structure
      is experimentally evaluated in this work. In order to achieve high control
      performance, advanced flexible piezoelectric actuator whose commercial name is
      Macro-Fiber Composite (MFC) is adapted to the shell structure. Governing equation
      is derived by finite element method and dynamic characteristics are investigated
      from the modal analysis results. Ring-stiffened cylindrical shell structure is
      then manufactured and modal test is conducted to verify modal analysis results.
      An optimal controller is designed and experimentally realized to the proposed
      shell structure system. Vibration control performance is experimentally evaluated
      in time domain and verified by simulated control results.

PMID- 25942821
TI  - Biomimetic walking trajectory generation of humanoid robot on an inclined surface
      using Fourier series.
AB  - This article describes a novel method to generate a biomimetic walking trajectory
      for a biped humanoid robot on an inclined surface. We assume that the
      configuration of the inclined surface is known, and we solve the human-like
      walking trajectory generation problem by obtaining the solution from the desired
      zero moment point (ZMP) trajectory to the center of gravity (CoG) trajectory. We
      present an analytic solution for the walking trajectory generation by using
      Fourier series. From the given ZMP trajectory biomimetically represented by the
      Fourier series, we focus on how to find the CoG trajectory in an analytical way.
      A time-segmentation based approach is adopted for generating the trajectories.
      The trajectory functions need to be continuous between the segments; thus, the
      solution is found by calculating the coefficients under these connectivity
      conditions. We derive a general form of the ZMP equation using a simple inverted
      pendulum model (SIPM), which includes the ZMP and the CoG trajectories in the
      horizontal and vertical directions to quantify the walking parameters on the
      inclined surface. The performance of the proposed approach is verified by
      conducting walking simulations using a full-body dynamic simulator on three
      different inclined surfaces and comparing them to the authors' previous approach.

PMID- 25942822
TI  - Analysis of temperature distribution during tension test of glass fiber
      reinforced plastic by fiber orientation variation.
AB  - In this paper, analysis of temperature distribution by fiber orientation
      variation under tension test was proposed through IR thermography camera. Lock-in
      method, which is one of technique in IR thermography camera to measure minute
      change in temperature, was utilized to monitor temperature distribution and
      change during crack propagation. Method to analyze of temperature distribution by
      fiber orientation variation under tension test of GFRP via IR thermography camera
      was suggested. At the maximum stress point, temperature was significantly
      increased. As shown previously, specimen with shorter fracture time showed abrupt
      increment of temperature at the maximum stress point. Specimen with longer
      fracture time displayed increment of temperature after the maximum stress point.

PMID- 25942823
TI  - Metal oxide coated lithium cobalt fluorophosphate cathode materials for lithium
      secondary batteries--effect of aging and temperature.
AB  - Lithium cobalt fluorophosphate (Li2CoPO4F) is a promising 5 V class cathode
      material for lithium secondary batteries. In this study, surface coating with
      ZrO2 improved the electrochemical activity of Li2CoPO4F with a maximum discharge
      capacity of 144 mA h g(-1). The effectiveness of ZrO2 coating was evaluated using
      aging analysis with a commercial electrolyte, i.e., 1 M LiPF6 in EC:DMC (1:1,
      v/v). The metal ion dissolution was reduced to 1/8th of that observed in the non
      coated Li2CoPO4F. It was found that the thin coating layer had less or no
      contribution to the additional resistance for the cell, both at an open circuit
      potential and at a fully charged state; hence, the capacity of the cell was
      retained over cycling. Elevated temperature aging did not affect the intrinsic
      property of the coated Li2CoPO4F, as observed from the complete anodic and
      cathodic peaks from cyclic voltammetry studies after 30 days of storage at 50
      degrees C. An increase in impedance was observed for aged cells, which could be
      due to the thick SEI layer formed during storage. The ZrO2 coating over Li2CoPO4F
      was crucial for the improved performance of electrode active material at higher
      operating potentials of up to 5.2 V.

PMID- 25942824
TI  - Fabrication and characterization of dry conducting polymer actuator by vapor
      phase polymerization of polypyrrole.
AB  - A trilayered dry conducting polymer actuator was fabricated via application of a
      polypyrrole (PPy) coating on both sides of a solid polymer electrolyte film using
      vapor phase polymerization (VPP). The solid polymer electrolyte film was prepared
      by incorporation of different weight ratios of dodecylbenzene sulfonic acid
      sodium salt in poly(vinyl alcohol) (PVA) by solvent casting. The successful
      polymerization of PPy was confirmed by Fourier transform infrared spectroscopy; a
      uniform PPy coating on the solid polymer electrolyte film surface was also
      observed by scanning electron microscopy. The dry PVA/PPy actuator demonstrated
      good actuation behavior at a low applied voltage of 1-3 V. The actuator bending
      displacement was found to increase with an increase in the applied voltage. The
      VPP approach in this study provides a very effective method for achieving a
      uniform polymer coating in the fabrication of a dry conducting polymer actuator.

PMID- 25942825
TI  - Synthesis of cellulose-L-tyrosine-silica hybrid nanocomposites by sol-gel process
      for high performance applications.
AB  - Cellulose is the most abundant bio-renewable materials with a long and well
      established technological base products and important applications such as fiber
      and paper materials. The one dimensional nano-materials such as nanotubes,
      nanowires and nano-rods have been widely studied for their potential applications
      in the field of nano-devices and nano-sensors due to their excellent electronic,
      optical properties. In this present work, the homogeneous cellulose-L-tyrosine
      silica hybrid materials is prepared by in-situ sol-gel process using TEOS and
      gamma-aminopropyltriethoxysilane (gamma-APTES) as coupling agent. The silica nano
      materials could be attached to the surface of amino functionalized cellulose-L
      tyrosine matrices. The covalent bonding behavior of silica were characterized by
      Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy
      (SEM), X-ray diffraction analysis (XRD) and transmission electron Microscopy
      (TEM).

PMID- 25942826
TI  - Assessment of hydro/oleophobicity for shark skin replica with riblets.
AB  - The shark skin has a unique skin structure which enables the shark to swim faster
      and more efficiently due to an intriguing three-dimensional rib pattern. Shark
      skin has also known as having functional performances such as self cleaning and
      anti-fouling as well as excellent drag reduction due to a hierarchical structure
      built up by micro grooves and nano-long chain mucus drag reduction interface
      around the shark body. In this study, the wetting properties for the biomimetic
      surfaces that replicate shark skin are assessed. First of all, the shark skin
      replicas are obtained using the micro molding technique directly from a shark
      skin template. The quantitative replication precision of the shark skin replicas
      is evaluated comparing with the geometry of shark skin template using 3D and 2D
      surface profiles are measured. Then contact angles in the conditions of solid-air
      water, solid-air-oil and solid-water-oil interfaces are evaluated for shark skin
      replicas. The effect of Teflon coating on the wetting properties of shark skin
      replicas is also observed. The results show the shark skin replica by the micro
      molding technique gives better effect on the wetting performance, and the micro
      riblets on shark skin improve the wettability feature.

PMID- 25942827
TI  - Nanotube nucleation phenomena on Ti-25Ta-xZr alloys for implants using ATO
      technique.
AB  - The purpose of this study was to investigate nanotube nucleation phenomena on the
      Ti-25Ta-xZr alloys for implant materials, using an anodic titanium oxide (ATO)
      technique. Ti-25Ta-(0 wt.%-15 wt.%) Zr alloys were prepared using a vacuum arc
      melting furnace. The Ti-25Ta-xZr alloys were then homogenized for 12 hr at 1000
      degrees C, followed by water quenching. Formation of the nanotubular oxide
      surface structure was achieved initially on the Ti-25Ta-xZr alloys by anodization
      in a 1 M H3PO4 electrolyte containing 0.8 wt.% NaF at room temperature, using a
      potentiostat. After the first formation of the nanotubes was achieved, this
      initial nanotube layer was eliminated, and further anodization was carried out
      repeatedly. The microstructure, phase transformation, and morphology of
      nanotubular Ti-25Ta-xZr alloys and the process of nanotube growth using this ATO
      method were analyzed by X-ray diffraction, field-emission scanning electron
      microscopy, and energy dispersive X-ray spectroscopy. Microstructures of the Ti
      25Ta-xZr alloys changed from alpha" phase to beta phase. Nanotubes formed with
      the ATO technique had pit-like top holes, with thinner walls and lower contact
      angle, compared to the initially formed nanotubes.

PMID- 25942828
TI  - Encapsulated particles attached on electrospun fibers by in situ combination of
      electrospinning and coaxial electrospraying.
AB  - Electrohydrodynamic jetting has been widely used as a promising strategy for the
      development of functionalized scaffolds to mimic natural extracellular matrix.
      The current electrospun scaffolds achieve functionality through additional
      mechanical or chemical treatments, and their life-time depends on fiber
      degradation. An innovative in situ approach used to attach core-shell poly(D,L
      lactide-co-glycolide) (PLGA) particles on fibrous mats is described here. This
      particle/fiber composite was prepared by electrohydrodynamic jetting of
      countercharged nozzles (EJC) based on neutralization between electrospun
      nanofibers and coaxial electrosprayed droplets. The PLGA particles were
      successfully attached onto both water-soluble polyvinylpyrrolidone and
      hydrophobic poly(L-lactide-co-D,L-lactide). The resulting release rates of
      encapsulated model compounds were independently controlled by fiber degradation.
      Encapsulation efficiency and the dimensions of particles and fibers were easily
      engineered by changing solvents. The particle/fiber composite prepared by EJC
      could be a superior material for developing future biomaterials with
      architectured biological and mechanical properties.

PMID- 25942829
TI  - Hydroxyapatite precipitation on nanotube surfaces of Ti-35Ta-xNb alloys.
AB  - Hydroxyapatite precipitation on nanotube surfaces of Ti-35Ta-xNb alloys was
      investigated using electrochemical methods. The alloys were prepared by arc
      melting, heat treated at 1050 degrees C for 12 h in an Ar atmosphere, and
      quenched in 0 degrees C water. Nanotubes were created on the Ti-35Ta-xNb alloys
      in a 1 M H3PO4 + 1.2 wt.% NaF electrolyte at room temperature. Hydroxyapatite
      precipitation was carried out in a 0.03 M Ca(NO3)2 x 4H2O + 0.018 M NH4H2PO4
      solution at 80 +/- 1 degrees C, using 10 deposition cycles. Information about
      morphology and composition was obtained by FE-SEM and EDS. The microstructure of
      the Ti-35Ta-xNb alloys was transformed from alpha phase to betaphase as the Nb
      content increased. The HA precipitates had a plate-like morphology on bulk Ti
      35Ta-xNb alloys and a flower-like morphology on nanotubular Ti-35Ta-xNb alloys.

PMID- 25942830
TI  - Compliant topology optimization for planar passive flap micro valve.
AB  - This paper reports the compliant topology optimization for planar passive flap
      micro valve considering fluid-structure interaction with a monolithic approach.
      Although flap valve type check valve is easy to manufacture and use for the
      applications for Bio/Nano/MEMS, its structural optimization has been seldom
      conducted so far. The size of the Bio/Nano/MEMS devices becomes smaller and the
      simple straight type micro valve structure is required to be optimized
      considering fluid speed. To address this optimization problem, the structural
      topology optimization scheme which designs optimal topologies is applied for a
      flap type check valve structure. To consider the coupling effects of fluid domain
      and structural domain, the monolithic finite element approach is employed. In the
      new analysis approach, solid domain is simulated by introducing the inverse
      permeability in the Navier-Stokes equation and the fluid stress filter in the
      linear elasticity equation. Also it is a new idea that fluid domain is simulated
      by finite elements with a weak Young's modulus in the linear elasticity equation.
      The mutual couplings between fluid and structure are considered by the
      introduction of the deformation tensor which is one of the basic concepts of the
      continuum mechanism. By distributing material properties inside a design domain
      for compliant flap, optimal flap structures can be constructed with different
      fluid speeds. By investigating the optimal layouts of several passive flap
      designs, we prove that the structural topology optimization can provide optimal
      layouts for Bio, Nano, and MEMS applications.

PMID- 25942831
TI  - Application of nonlocal models to nano beams. Part I: Axial length scale effect.
AB  - Applicability of nonlocal models to nano-beams is discussed in terms of physical
      implications via the similarity between a nonlocal Euler-Bernoulli (EB) beam
      theory and a classical Rankine-Timoshenko (RT) beam theory. The nonlocal EB beam
      model, Eringen's model, is briefly reviewed and the classical RT beam theory is
      recast by the primary variables of the EB model. A careful comparison of these
      two models reveals that the scale parameter used to the Eringen's model has a
      strike resemblance to the shear flexibility in the RT model. This implies that
      the nonlocal model employed in literature consider the axial length scale effect
      only. In addition, the paradox for a cantilevered nano-beam subjected to tip
      shear force is clearly explained by finding appropriate displacement prescribed
      boundary conditions.

PMID- 25942832
TI  - Application of nonlocal models to nano beams. Part II: Thickness length scale
      effect.
AB  - Applicability of nonlocal models to nano-beams is discussed in terms of the
      Eringen's nonlocal Euler-Bernoulli (EB) beam model. In literature, most work has
      taken the axial coordinate derivative in the Laplacian operator presented in
      nonlocal elasticity. This causes that the non-locality always makes the beam
      soften as compared to the local counterpart. In this paper, the thickness scale
      effect is solely considered to investigate if the nonlocal model can simulate
      stiffening effect. Taking the thickness derivative in the Laplacian operator
      leads to the presence of a surface stress state. The governing equation derived
      is compared to that of the EB model with the surface stress. The results obtained
      reveal that the nonlocality tends to decrease the bending moment stiffness
      whereas to increase the bending rigidity in the governing equation. This tendency
      also depends on the surface conditions.

PMID- 25942833
TI  - Formation control for a network of small-scale robots.
AB  - In this paper, a network of small-scale robots (typically centimeter-scale
      robots) equipped with artificial actuators such as electric motors is considered.
      The purpose of this network is to have the robots keep a certain formation shape
      (or change to another formation shape) during maneuvers. The network has a fixed
      communication topology in the sense that robots have a fixed group of neighbors
      to communicate during maneuvers. Assuming that each robot and its actuator can be
      modeled as a linear system, a decentralized control law (such that each robot
      activates its actuator based on the information from its neighbors only) is
      introduced to achieve the purpose of formation keeping or change. A linear matrix
      inequality (LMI) for deriving the upper bound on the actuator's time constant is
      also presented. Simulation results are shown to demonstrate the merit of the
      introduced control law.

PMID- 25942834
TI  - Optimization of the surface immobilized folate on the magnetic nanoparticles.
AB  - Cancer cells overexpressing folate receptors have been targeted using a folate
      decorated carriers for anti-cancer drugs in aims to overcome the tissue non
      specificity of anti-cancer agents. We here prepared magnetic nanoparticles and
      surface-decorated them with different amounts of folate to optimize the number of
      the immobilized folate on the carriers for superior targeting effects. Magnetic
      nanoparticles were prepared by oxidizing ferric or ferrous chloride solution to
      iron oxide in the presence of poly(vinyl alcohol). The magnetic nanoparticles
      were functionalized with primary amines for subsequent reactions with the
      different feed ratios of the activated folate. The magnetization degree of the
      folate magnetic magnetization were slightly decreased when the folate on the
      particles were increased. Intracellular uptakes of the nanoparticles were shown
      to be increased and become saturated dependent on the amounts of the surface
      immobilized folate. The folate-decorated magnetic nanoparticles showed negligible
      cytotoxicity against KB cells from 5 MUg to 35 MUg of the nanoparticle weights.

PMID- 25942835
TI  - Preparation of biomimetic high adhesive superhydrophobic polymer pillar surfaces
      with crown-like metal microstructures.
AB  - High adhesive superhydrophobic polymer pillar surfaces with dispersed metallic
      crown-like micro structures were prepared by electroless plating on self
      organized honeycomb patterned polymer films and peeling off the top layer of the
      metal covered honeycomb films. Thus obtained polymer pillar surfaces with
      metallic crown-like microstructures possessed conflicting properties of water
      repellency and adhesion. The adhesion property was tuned by number density of
      metallic crown-like microstructures which were adjusted by polymer concentration
      in a catalytic solution for electroless plating.

PMID- 25942836
TI  - Influence of process parameters on the content of biomimetic calcium phosphate
      coating on titanium: a Taguchi analysis.
AB  - In this study, a statistical design of experimental methodology based on Taguchi
      orthogonal design has been used to study the effect of various processing
      parameters on the amount of calcium phosphate coating produced by such technique.
      Seven control factors with three levels each including sodium hydroxide
      concentration, pretreatment temperature, pretreatment time, cleaning method,
      coating time, coating temperature and surface area to solution volume ratio were
      studied. X-ray diffraction revealed that all the coatings consisted of the
      mixture of octacalcium phosphate (OCP) and hydroxyapatite (HA) and the presence
      of each phase depended on the process conditions used. Various content and size (
      1-100 MUm) of isolated spheroid particles with nanosized plate-like morphology
      deposited on the titanium surface or a continuous layer of plate-like
      nanocrystals having the plate thickness in the range of -100-300 nm and the plate
      width in the range of 3-8 MUm were formed depending on the process conditions
      employed. The optimum condition of using sodium hydroxide concentration of 1 M,
      pretreatment temperature of 70 degrees C, pretreatment time of 24 h, cleaning by
      ultrasonic, coating time of 6 h, coating temperature of 50 degrees C and surface
      area to solution volume ratio of 32.74 for producing the greatest amount of the
      coating formed on the titanium surface was predicted and validated. In addition,
      coating temperature was found to be the dominant factor with the greatest
      contribution to the coating formation while coating time and cleaning method were
      significant factors. Other factors had negligible effects on the coating
      performance.

PMID- 25942837
TI  - Fabrication of conductive polymer-based nanofiber scaffolds for tissue
      engineering applications.
AB  - Natural and synthetic polymers, in particular those that are conductive, are of
      great interest in the field of tissue engineering and the pursuit of biomimetic
      extracellular matrix (ECM) structures for adhesion, proliferation, and
      differentiation of cells. In the present study, natural chitin and conductive
      polyaniline (PANi) blended solutions were electrospun to produce biodegradable
      and conductive biomimetic nanostructured scaffolds. The chitin/PANi (Chi-PANi)
      nanofibrous materials were characterized using field emission scanning electron
      microscopy, Fourier transform-infrared spectroscopy, wettability analysis,
      mechanical testing, and electrical conductivity measurements using a 4-point
      probe method. The calculated electrical conductivities of the PANi-containing
      nanofiber scaffolds significantly increased as the amount of PANi increased,
      reaching 5.21 +/- 0.28 x 10(-3) S/cm for 0.3 wt% content of the conducting
      polymer. In addition, the viability of human mesenchymal stem cells (hMSCs)
      cultured on the Chi-PANi nanofiber scaffolds in vitro was found to be excellent.
      These results suggest that the Chi-PANi nanofiber scaffolds have great potential
      for use in tissue engineering applications that involve electrical stimulation.

PMID- 25942838
TI  - Colloidal particle assembly using piezoelectric inkjet printing of polystyrene
      colloidal ink formulations.
AB  - We report the feasibility of piezoelectric inkjet printing of colloidal
      dispersion inks for geometrical patterning to arrange colloids in desired
      locations. Polystyrene colloid (dia. = 3 MUm) inks dispersed with thermally
      curable binder in organic solvents are explored for fundamental study on
      colloidal patterning. The inkjet printability of colloidal inks is systematically
      investigated with different ink formulations and inkjet process variables. In
      addition, in order to maintain the structural stability of colloidal patterns
      fabricated on the substrate from externally applied forces such as mechanical,
      chemical and thermal stimuli, thermally curable binder was formulated into the
      colloidal ink formulations.

PMID- 25942839
TI  - Monitoring of surface roughness of plasma-deposited films using optical
      microscopy-measured dark particle distributions.
AB  - We present a dark field microscopy for the measurement of film surface roughness.
      The underlying principle is that a darker region in a film surface represents a
      deeper place from the top surface. The performance of the imaging system was
      demonstrated for silicon nitride films deposited in a SiH4-NH3 plasma. The system
      provided distributions of particles and the tendency of particle counts was
      compared with that of AFM-measured surface roughness. A strong correlation
      identified between them represents that the system is a viable alternative to
      AFM. The system is expected to find applications to roughness measurement during
      a real-time plasma processes.

PMID- 25942840
TI  - Improvement of dispersion stability and optical properties of CdSe/ZnSe
      structured quantum dots by polymer coating.
AB  - In this study, CdSe core and CdSe/ZnSe core/shell quantum dots with a narrow size
      distribution were synthesized in a micro-reactor. A PMMA coating applied to the
      surface of CdSe/ZnSe core/shell QDs to prevent degradation gave improved
      dispersion stability compared to the CdSe core and CdSe/ZnSe core/shell. Many
      previous approaches to dispersion stability have not been quantitatively
      assessed. The dispersion stability was confirmed by multiple light scattering
      measurement. Additionally, the PMMA-coated CdSe/ZnSe QDs showed greatly improved
      optical properties with a photoluminescence quantum yield up to 80%. This
      structural motif is expected to prevent the degradation of QDs.

PMID- 25942841
TI  - In-situ P doped epitaxial Si(1-x)C(x) growth under UHV-CVD.
AB  - Undoped and in-situ phosphorus-doped epitaxial Si(1-x)C(x) layers were grown on
      chemically cleaned Si (100) substrates by using a UHV-CVD process. The carbon
      concentrations of the epitaxial layers and growth temperatures were varied, and
      the effects of post annealing processes were then investigated. In the defect
      free films, the carbon content in the Si(1-x)C(x) layer was analyzed to be about
      1.2% by XRD measurement. About 20% loss of the substitutional carbon atoms
      occurred after annealing treatment at 1000 degrees C in N2 ambient due to the
      transfer of the substititual carbon atoms to interstitial sites as well as the
      formation of the beta-SiC precipitates. The changes in microstructures were
      analyzed by the cross sectional transmission electron microscopy. The surface of
      the films shows partially polycrystalline structures in high PH, flow rate, due
      to surface poisoning by phosphorus segregation. Fully a 100% substitutionality of
      carbon atoms in the epitaxial Si(1-x)C(x) film is achieved by the addition of PH3
      and post annealing.

PMID- 25942842
TI  - Fabrication and characterization of quantum dots-bound hydrogels with fluorescent
      and temperature-sensitive functionalities.
AB  - In this work, dual-functional composite particles possessing fluorescence and
      temperature-sensitive functionalities were developed in the form of QD-bound
      hydrogels for biomedical applications. First, the surface of silica nanoparticles
      (SNPs) was functionalized with olefin silanes, followed by hydrogel encapsulation
      through a radical polymerization. The encapsulated hydrogels were poly(N-
      isopropylacrylamide-co-acrylic acid) P(NIPAM-co-AAc) copolymer, showing the
      sensitive volume changes corresponding to the alternating temperature changes
      between 25 degrees C and 45 degrees C. At an optimal pH5, the hydrogel
      encapsulated SNPs (SiO2@hydrogel) were effectively anchored by amino quantum dots
      (amino-QDs) through electrostatic (attractive) interactions between carboxylate
      groups of hydrogels and amine groups of QDs. QD-bound hydrogels with co-monomer
      ratio of [NIPAM:AAc = 83:17 wt%] exhibited the higher PL intensity than other
      samples with [NIPAM:AAc = 96:4 wt% or 91:9 wt%], indicating that higher fraction
      of carboxylate groups by AAc induced the effective bounding with QDs possessing
      positively charged amine groups.

PMID- 25942843
TI  - Air atmospheric pressure plasma jet pretreatment for drop-wise loading of
      dexamethasone on hydroxyapatite scaffold for increase of osteoblast attachment.
AB  - Periodontal disease affects alveolar bone resorption around the involved teeth.
      To gain bone height, bone graft materials have been widely used with drug
      carriers. Application of an atmospheric pressure plasma jet (APPJ) treatment is
      widely studied due to its ability to change surface characteristics without
      topographical change. The aim of this study is to identify whether the air APPJ
      (AAPPJ) treatment before drop-wise loading performance could change loaded amount
      of dexamethasone, and induce increase of cell attachment and proliferation. The
      results suggested that AAPPJ treatment decreased the contact angle down to about
      13 degrees, which increased gradually but significantly lowered at least 4 days
      compared to no-treated group. After AAPPJ treatment, hydrocarbon was removed with
      change of zeta potential into positive charge. However, the AAPPJ treatment did
      not change the quantity or releasing profile of dexamethasone (p > 0.05).
      Confocal analysis combined with DNA proliferation analysis showed increase of
      osteoblast attachment and proliferation. Hence, AAPPJ could be a useful
      pretreatment method before drop-wise loading on HA scaffold with dexamethasone
      for increase of osteoblast attachment.

PMID- 25942844
TI  - Controllable synthesis of thiol-capped CdTe nanoparticles for optical sensing of
      triethylenetetramine dihydrochloride.
AB  - Highly luminescent CdTe quantum dots (QDs) were synthesized through a co
      precipitation route in aqueous salt solutions using different thiols as
      stabilizers. The synthetic procedure was simple, efficient, and stable. It could
      also allow controlling the emission wavelength by varying the experimental
      conditions such as reaction time and pH values. The strong luminescence of the
      QDs was observed under UV-excitation and emission colors could be adjusted. The
      interaction between CdTe QDs and triethylenetetramine dihydrochloride (TETA)
      which is a candidate treatment for diabetic cardiovascular complication was
      investigated by fluorescence spectroscopy. Based on the quenching effect on CdTe
      photoluminescence intensity by TETA, a simple assay system for analyzing the
      content of TETA in aqueous samples was developed. The linearity was maintained in
      the range of 0.2 MUM to 1.2 MUM (R2 = 0.994) with a limit of detection (LOD; S/N
      = 3) at 28 nM. The results showed that CdTe QDs capped with diverse thiols has a
      potential for the quantitative analysis of TETA in urine samples.

PMID- 25942845
TI  - Performance and durability of anode-supported flat-tubular solid oxide fuel cells
      with Ag-infiltrated cathodes.
AB  - An anode-supported flat-tubular solid oxide fuel cell is an advanced cell design,
      which offers many advantages including a high volumetric power density, a
      minimized sealing area and a high resistance to thermal cycling. Infiltration of
      nano-sized noble metal catalysts into a porous cathode is known to be an
      effective method to improve cathode performances at reduced temperatures, but the
      cathode stability is of potential concern. This study addresses the performance
      and durability of anode-supported flat-tubular solid oxide fuel cells with Ag
      infiltrated cathodes. Uniformly dispersed Ag nanoparticles on the cathode are
      formed via a wet infiltration technique combined with subsequent heat-treatment.
      Although the Ag infiltration results in improved cell performance, the durability
      tests indicate that the cell performance degrades over time and that the
      degradation rate increases with increasing Ag loading in the cathode. The
      observed performance degradation is mainly attributed to formation of large-scale
      Ag agglomerates. A strategy based on an inter-dispersed composite of Ag and CeO2
      nanoparticles is proposed to mitigate the performance degradation.

PMID- 25942846
TI  - Strategies for the modification of adhesion at graphene/Al Interfaces: a first
      principles study.
AB  - Possibility of improving the adhesion at graphene/Al interfaces has been
      investigated by predicting interactions between monolayer graphene and Al (111)
      plane using first principles simulations. For the property modifications, either
      Ni atoms were adsorbed on one side of the graphene or the graphene is
      substitutionally doped with B. It was predicted that the adatoms or dopants
      modify local electronic or orbital structure, which subsequently promotes the
      bonding between the graphene and Al at local level thereby improving the bond
      strength at the interface. While improvement of interfacial properties was
      expected with the surface modification by a foreign element adsorption or
      substitutional doping of the graphene, low-concentration substitutional doping
      was predicted to be more effective in achieving improved adhesive properties of
      the graphene/Al nanointerface.

PMID- 25942847
TI  - Size and shape effect of SiC source/drain on strained Si.
AB  - Strained Si is used to enhance carrier mobility in MOSFET devices. Epi-grown Si(1
      x)C(x) as a source/drain induces strain on a channel because its lattice constant
      is smaller than Si. The distribution of stress varies with the layout of the
      device and can involve gate length, source/drain width, elevation height, etc. In
      this work, we report on how these parameters effect channel strain by employing
      the Finite Element Method. A 3-dimensional model and anisotropic properties such
      as the elastic constant and Poisson's ratio were adopted for high accuracy.
      Si0.983C0.017 was used as the source/drain on a Si substrate. The lateral channel
      strain was calculated based on a 30-90 nm gate length, a 30-90 nm source/drain
      width and 0-30 nm elevated source/drain shapes. The results showed that, when the
      gate length is longer, the channel strain is lower. On the other hand,
      source/drain width affects channel strain in a reverse manner. For models with
      the same gate length and source/drain width: 30, 60, 90 nm, the average channel
      strain is lower when the gate length and source/drain width are shorter. An
      additional parameter, namely, source/drain elevation height, was also studied.
      Interestingly, the effect of elevated shape is dependent on gate length and
      source/drain width.

PMID- 25942848
TI  - Effects of interdigitated platinum finger geometry on spectral response
      characteristics of germanium metal-semiconductor-metal photodetectors.
AB  - We fabricated interdigitated germanium (Ge) metal-semiconductor-metal
      photodetectors (MSM PDs) with interdigitated platinum (Pt) finger electrodes and
      investigated the effects of Pt finger width and spacing on their spectral
      response. An increase in the incident optical power enhances the creation of
      electron-hole pairs, resulting in a significant increase in photo current.
      Lowering of the Schottky barrier could be a main cause of the increase in both
      photo and dark current with increasing applied bias. The manufactured Ge MSM PDs
      exhibited a considerable spectral response for wavelengths in the range of 1.53
      1.56 MUm, corresponding to the entire C-band spectrum range. A reduction in the
      area fraction of the Pt finger electrode in the active region by decreasing and
      increasing finger width and spacing, respectively, led to an increase in
      illuminated active area and suppression of dark current, which was responsible
      for the improvement in responsivity and quantum efficiency of Ge MSM PDs.

PMID- 25942849
TI  - Nanoscale amorphization of GeTe nanowire with conductive atomic force microscope.
AB  - We fabricated GeTe nanowires by using Au catalysis mediated vapor-liquid-solid
      method. The fabricated nanowires were confirmed by X-ray diffraction, scanning
      electron microscopy and transmission electron microscopy. For a nanowire with -
      150 nm diameter, we performed amorphization experiment with conductive atomic
      force microscope. We examined the structural change of the nanowire with several
      bias voltages from 0 V to 10 V. Above bias voltage of 6-7 V, some points of the
      nanowire showed transition to amorphous phase. The consumed energy for the
      amorphization was estimated to be 4-5 nJ, which was close to the other result of
      nanowire tested with a four probe device.

PMID- 25942850
TI  - Vancomycin-lnduced fluorescence and morphological changes in bis(dipeptide)
      containing biphenyl supramolecules.
AB  - A biphenyl derivative containing two D-Ala-D-Ala moieties was found to form
      fluorescent nano/microfibers when subjected to self-assembly conditions in
      aqueous EtOH. Incubation of the nano/microfibers with vancomycin results in the
      disappearance of the fibers along with a significant decrease in the fluorescence
      intensity. The detection limit of vancomycin determined by the fluorescence
      quenching strategy was calculated to be ca. 57 MUM. Regeneration of the original
      fiber structures were obtained in the presence of Ac-Lys(Ac)-D-Ala-D-Ala, a
      substance known to bind tightly to vancomycin. Other proteins including bovine
      serum albumin (BSA), casein, elastase, and chymotrypsin were found to cause no
      morphological and fluorescence changes in the supramolecules. The unique
      vancomycin-induced phase transition and fluorescence change were not observed
      with a biphenyl derivative having L-Ala-L-Ala moiety.

PMID- 25942851
TI  - Study on the impact of fiber length on the correlation of separation and
      orientation in flow molded glass fiber-reinforced plastic composites.
AB  - During the compression molding of fiber-reinforced plastic composites, there are
      two issues: one is separation of fiber and matrix because of the different flow
      state and fiber orientation. Due to separation and orientation, moldings become
      nonhomogeneous, and show anisotropy. Therefore, separation and orientation should
      be closely corresponded to molding condition and fiber structure. If fiber shows
      strong agglomeration, it increases the separation, but fiber orientation will be
      limited. That is, separation and orientation of fiber is closely related, and the
      relationship should be clearly defined. In this study, fiber content and length
      is varied for stacked laminates, and primary sheet is fabricated with thermal
      compression press. Primary sheet is heated and molded with 30-ton hydraulic
      press. Nonhomogeneity, one of indicators for separation, is measured from one
      dimensional rectangular plate after compression. Orientation function is
      calculated using X-ray image on moldings and image scanner for processing imagery
      data. From the correlation between the separation and the orientation of fiber
      and matrix, the correlation coefficient is defined, and the impact of fiber
      length on the coefficient is evaluated.

PMID- 25942852
TI  - Influence of TiCl4 post-treatment condition on TiO2 electrode for enhancement
      photovoltaic efficiency of dye-sensitized solar cells.
AB  - Titanium tetrachloride (TiCl4) treatment processed by chemical bath deposition is
      usually adopted as pre- and post-treatment for nanocrystalline titanium dioxide
      (TiO2) film deposition in the dye-sensitized solar cells (DSSCs) technology.
      TiCl4 post-treatment is a widely known method capable of improving the
      performance of dye-sensitized solar cells. In this work, the effect of TiCl4 post
      treatment on the TiO2 electrode is proposed and compared to the untreated film. A
      TiO2 passivating layer was deposited on FTO glass by RF magnetron sputtering. The
      TiO2 sol prepared sol-gel method, nanoporous TiO2 upper layer was deposited by
      screen printing method on the passivating layer. TiCl4 post-treatment was
      deposited on the substrate by hydrolysis of TiCl4 aqueous solution. Crystalline
      structure was adjusted by various TiCl4 concentration and dipping time: 20 mM-150
      mM and 30 min-120 min. The conversion efficiency was measured by solar simulator
      (100 mW/cm2). The dye-sensitized solar cell using TiCl4 post-treatment was
      measured the maximum conversion efficiency of 5.04% due to electron transport
      effectively. As a result, the DSSCs based on TiCl4 post-treatment showed better
      photovoltaic performance than cells made purely of TiO2 nanoparticles. The
      relative DSSCs devices are characterized in terms of short circuit current
      density, open circuit voltage, fill factor, conversion efficiency.

PMID- 25942853
TI  - Effects of target angle on the properties of aluminum doped zinc oxide films
      prepared by DC magnetron sputtering for thin film solar cell applications.
AB  - An aluminum doped zinc oxide (AZO) films for front contacts of thin film solar
      cells, in this work, were prepared by DC magnetron sputtering with different
      target angles. Effects of target angles on the structural and electro-optical
      properties of AZO films were investigated. Also, to clarify the light trapping of
      textured AZO film, amorphous silicon thin film solar cells were fabricated on the
      textured AZO/glass substrate and the performance of solar cells were studied. The
      surface became more irregular with increasing the target angle due to larger
      grains. The self-surface textured morphology, which is a favorable property as
      front layer of solar cell, exhibited at target angle of 72.5 degrees. We obtained
      the films with various opto-electronic properties by controlling target angle
      from 32.5 degrees to 72.5 degrees. The spectral haze increased substantially with
      the target angle, whereas the electrical resistivity was increased. The
      conversion efficiency of amorphous silicon solar cells with textured AZO film as
      a front electrode was improved by the increase of short-circuit current density
      and fill factor, compared to cell with relatively flat AZO films.

PMID- 25942854
TI  - Physical and electrochemical characterization of 0.3Li2MnO3 x
      0.7LiMn0.60Ni0.25Co0.15O2 material for Li secondary battery.
AB  - The 0.3Li2MnO3 x 0.7LiMn0.60Ni0.25Co0.15O2 cathode materials were synthesized
      using a coprecipitation method at a various heat-treatment temperature. From XRD
      pattern analysis, pure layered structure without impurities was confirmed from
      all samples and the peak intensity of Li2MnO3 was increased as the heat-treatment
      temperature increased. The primary particle size increased approximately from 100
      nm to 500 nm with increasing heat-treatment temperature. The initial discharge
      capacity of the materials obtained at 950 degrees C was 235 mA h/g at 0.1 C rate,
      but then decreased down to 228 mA h/g with further increasing heat-treatment
      temperature. And, in the voltage range of 2.0-4.6 V, the electrode heat-treated
      at 900 degrees C showed the highest capacity retention of 68% at 5 C rate against
      to 0.1 C rate.

PMID- 25942855
TI  - Densification and microstructure of the gas-atomized Cu-15%Ga alloy powder by
      cross-roll rolling.
AB  - In this study, the gas-atomized Cu-15%Ga alloy powder was consolidated by cross
      roll rolling using copper can without crack and oxidation, where the roll axis
      was tilted by 5 degrees against TD in the RD-TD plane. Microstructures of formed
      Cu-15%Ga alloy were examined by X-ray diffraction (XRD), scanning electron
      microscopy (SEM), electron backscatter diffraction (EBSD) and optical microscopy
      (OM). Density of the cross-roll rolled specimens was measured using Archemeded
      method. Also, the porosity was examined by an image analyzer. The porosity of the
      cross-roll rolled samples with rolling reduction of 60% was approximately 6.7
      times lower than that of the CR-rolled samples at 40% at a rolling temperature to
      850 degrees C. The specimen obtained with 5 degrees of cross-roll rolling degree
      and 60% of rolling reduction ratio at 850 degrees C was above 99% to the
      theoretical density and an average grain size was 19.2 MUm.

PMID- 25942856
TI  - Phase transition and thermal expansion studies of alumina thin films prepared by
      reactive pulsed laser deposition.
AB  - Aluminium oxide (Al2O3) thin films were deposited on Si (100) substrates at an
      optimized oxygen partial pressure of 3 x 10(-3) mbar at room temperature by
      pulsed laser deposition (PLD). The films were characterized by high temperature X
      ray diffraction (HTXRD), field emission scanning electron microscopy (FESEM) and
      atomic force microscopy (AFM). The HTXRD pattern showed the cubic y-Al2O3 phase
      in the temperature range 300-973 K. At temperatures >= 1073 K, the delta and
      theta-phases of Al2O3 were observed. The mean linear thermal expansion
      coefficient and volume thermal expansion coefficient of gamma-Al2O3 was found to
      be 12.66 x 10(-6) K(-1) and 38.87 x 10(-6) K(-1) in the temperature range 300 K
      1073 K. The field emission scanning electron microscopy revealed a smooth and
      structureless morphology of the films deposited on Si (100). The atomic force
      microscopy study indicated the increased crystallinity and surface roughness of
      the films after annealing at high temperature.

PMID- 25942857
TI  - High-yield growth of carbon nanofilaments on nickel foam using nickel-tin
      intermetallic catalysts.
AB  - The integration of nanomaterials into macroscopic structures is of importance to
      their practical use. We report the direct synthesis of carbon nanofilaments on Ni
      foam using Ni-Sn intermetallic nanoparticles. The use of SnO2 nanoparticles was
      highly effective for the high-yield growth of carbon nanofilaments without the
      occurrence of surface breakup, resulting from excessive carbon accumulation in
      the Ni foam. Carbon nanofilaments with a diameter of 50 nm were synthesized and
      contained Ni3Sn nanoparticles at the tip, indicating a tip-growth mechanism.
      Higher vacuum conditions led to the growth of highly crystalline carbon
      nanofilaments. The results obtained using different sources of hydrocarbon
      revealed that in contrast to C2H2, CH4 or C3H8 did not induce carbon nanofilament
      formation on Ni foam.

PMID- 25942858
TI  - Nanoindentation hardness and elastic modulus of nano-grained titanium produced by
      asymmetric and symmetric rolling.
AB  - To understand the nanomechanical properties of nano-grained (NG) Ti produced by
      combination of asymmetric and symmetric rolling, nanoindentation hardness (H(n))
      and elastic modulus (E(n)) of different planes within the NG Ti specimens were
      measured using continuous stiffness measurement mode at room temperature. For
      comparison, the nanomechanical properties of the as-received hot-rolled coarse
      grained (CG) Ti and ultrafine-grained (UFG) Ti with only asymmetric rolling
      process were also investigated. It was found that H(n) of the Ti samples
      increased significantly with the decrease of grain sizes, while E(n) exhibited a
      slight decrease as the grain sizes decreased from CG to NG regime. The increase
      of H(n) was expected to be caused by higher density of dislocations and finer
      grains attained by severer plastic deformation, while the slight decrease of E(n)
      was considered as a result of the increased density of lattice defects and volume
      fraction of the grain boundary atoms. Furthermore, the nanomechanical properties
      of different planes of the Ti specimen exhibited a little difference which can be
      expressed as H(n(RD-TD)) > H(n(N-RD)) > H(n(TD-ND)) and E(n(RD-TD)) > E(n(ND-RD))
      > E(n(TD-ND)). These differences were ascribed to crystallographic textures
      formed by rolling deformation.

PMID- 25942859
TI  - Surface characteristics of HA coating and micro-pore formation on the Ti-25Nb-xHf
      alloys for dental materials.
AB  - Micro-pore formation on titanium surface can increase the adhesion strength with
      increment of surface area, and hydroxyapatite is effective coating materials as a
      main chemical constituent of bone tissue for biomedical field. The aim of this
      study was to investigate the surface characteristics of HA coating and micro-pore
      formation on the Ti-25Nb-xHf alloys for dental materials. The Ti-25Nb-xHf alloys
      consisted of (0 and 7) wt.% Hf contents which were manufactured by vacuum arc
      melting furnace. The homogenization was performed at 1000 degrees C for 12 h and
      water quenched. Anodization was carried out using an electrochemical method in 1
      M H3PO4 electrolyte. The HA films were deposited by plasma sputtering method. The
      microstructures of alloys were transformed from alpha" phase to beta phase by
      addition of Hf element, and needle-like structures were translated to an equiaxed
      structure as Hf content increased. The peaks of anatase and rutile showed on the
      anodized surface of these alloys. The number of micro-pore decreased, with
      presence of Hf content increased, whereas size of micro-pore increased. Anodized
      surface was covered with HA particles at surface and in holes. Contact angle
      value of HA coating on anodized surface was lower than that of non-coating
      surface.

PMID- 25942860
TI  - Photocatalytic reaction characteristics of the titanium dioxide supported on the
      long phosphorescent phosphor by a low pressure chemical vapor deposition.
AB  - This study investigated the photocatalytic behavior of titanium dioxide (TiO2)
      supported on the long phosphorescent materials. Nanocrystalline TiO2 was directly
      deposited on the plate of alkaline earth aluminate phosphor, CaAl2O4: Eu2+, Nd3+
      by a low pressure chemical vapor deposition (LPCVD). Photocatalytic reaction
      performance was examined with the decomposition of benzene gas by using a gas
      chromatography (GC) system under ultraviolet and visible light (lambda > 410 nm)
      irradiations. The LPCVD TiO2-coated phosphors showed active photocatalytic
      reaction under visible irradiation. The mechanism of the photocatalytic
      reactivity for the TiO,-coated phosphorescent phosphor was discussed in terms of
      the energy band structure and phosphorescence. The coupling of TiO2 with phosphor
      may result in energy band bending in the junction region, which makes the TiO,
      crystal at the interface to be photo-reactive under visible light irradiation.
      The fastest degradation of ben- zene gas occurred for the TiO,-coated phosphor
      prepared with 1 min deposition time (-150 nm thickness). The LPCVD TiO,-coated
      phosphor is also photo-reactive under darkness through the light photons emitted
      from the CaAl2O4 phosphor. In addition, the TiO2-coated phosphorescent phosphors
      were characterized by X-ray diffraction (XRD) and scanning electron microscopy
      (SEM).

PMID- 25942861
TI  - Synthesis of Fe3O4/SiO2/CeO2 core-shell magnetic and their application as
      photocatalyst.
AB  - The Fe3O4/SiO2/CeO2 core-shell magnetic has been successfully synthesized by
      three steps of hydrothermal, sonochemical and homogeneous precipitation by
      coating CeO2 nanoparticles onto Fe3O4/SiO2 magnetic core. The prepared samples
      were characterized by X-ray diffraction (XRD), Field-emission scanning electron
      microscopy (FESEM) connected with energy dispersive X-ray analysis system (EDS),
      high resolution transmission electron microscopy (HRTEM), Nitrogen adsorption
      desorption analyses (BET), and vibrating sample magnetometer (VSM). The
      photocatalytic activities for Fe3O4/SiO2/CeO2 core-shell magnetic under UV and
      visible lights were measured by determining the degradation rate of formic and
      oxalic acid in spiral reactor for 120 min. The amounts of CO2 generated during
      the process were compared between the magnetic catalyst and bare CeO2. After the
      finished photocatalytic degradation, the magnetic catalyst was recovered by
      external magnetic field at the end of each experiment. The results showed that
      the photocatalytic activity of Fe3O4/SiO2/CeO2 core-shell magnetic had higher
      than that of bare CeO2 and was found to be constant for three cycles of the
      recycled use.

PMID- 25942862
TI  - CO detection of hydrothermally synthesized Pt-loaded WO3 films.
AB  - Unloaded WO3 and 0.25-1.0 wt% Pt-loaded WO3 nanoparticles were synthesized by
      hydrothermal method using sodium tungstate dihydrate and sodium chloride as
      precursors in the acidic condition and further by the impregnation method using
      platinum acetylacetonate. Pt-loaded WO3 films on Al2O3 substrate interdigitated
      with Au electrodes were prepared by spin-coating technique. The temperature has
      an obvious influence on the response of sensors to CO gas. In order to determine
      the optimal operating temperatures, the response of WO3 sensors with different Pt
      loading concentrations towards 50-2000 ppm of CO in air was tested as a function
      of operating temperature of 150-350 degrees C. It was found that 1.0 wt% Pt
      loaded WO3 sensing film showed the highest response of - 469 at 2000 ppm CO (250
      degrees C). Therefore an optimal operating temperature of 250 degrees C was
      chosen for CO detection.

PMID- 25942863
TI  - Enhanced ethanol selectivity of flame-spray-made Au/ZnO thick films.
AB  - Sensing characteristics of the spin-coated Au/ZnO nanoparticles thick films with
      different Au concentrations have been studied for various gases, namely, CO, SO2,
      ethanol and acetone. The influence on a dynamic range of Au concentration on
      ethanol response (0.005-0.1 vol.%) of thick film sensor elements was studied at
      the operating temperatures ranging from 300 to 400 degrees C in the presence of
      dry air. The optimum Au concentration was found to be 0.5 mol%. 0.5 mol% Au
      exhibited an optimum ethanol response of 5.0 x 10(2) and a short response time
      (10 s) for ethanol concentration of 0.1 vol.% at 400 degrees C. Plausible
      mechanisms explaining the enhanced ethanol selectivity by thick films of Au/ZnO
      are discussed.

PMID- 25942864
TI  - Ag contact properties according to the front grid width and firing temperature
      for silicon solar cells.
AB  - The effect of peak firing temperature and grid width on the contact properties
      between Ag metal and silicon (n+ emitter) was investigated for screen-printed
      silicon solar cells. We confirmed the factors that control the specific contact
      resistance as follows: (1) the Ag coverage fraction on the silicon surface, d(2)
      the thickness of the glass layer and (3) the etching depth on the n+ emitter
      region. The lowest specific contact resistance (8.27 mOmega x cm2) was obtained
      at the optimum firing temperature (720 degrees C). We also found that the grid
      width affected the contact quality of Ag paste because the contact width related
      to the absorbed heat of samples in RTP system. For this reason, when the grid
      width was further reduced, meaning more heat absorption, more Ag crystallites
      grew and the glass layer thickened. Light I-V results of a 6-inch silicon solar
      cell with minimum busbar width were similar to the PC1D simulation results. The
      efficiency was improved by 0.2% with the reduction of the busbar width.

PMID- 25942865
TI  - Indium tin oxide-free PEDOT:PSS/SAM/MoO3/Au/MoO3 multilayer electrodes for
      organic solar cells.
AB  - A MoO3/Au/MoO3 (MAM) tri-layer structure was developed as a transparent, low
      resistance anode for use in organic solar cells. Transmittance was maximized at
      82% using symmetric bottom and top MoO3 layers (each of thickness 30 nm) either
      side of a 12 nm Au layer. Low sheet resistance also resulted (7.4 ohm per
      square). The series resistance and optical transmission of devices employing
      these structures as anodes were tailored by varying the thickness of the top MoO3
      layer. Dissolution of the top MoO3 layer in PEDOT: PSS degraded the cells, which
      could be decreased by the deposition of a self-assembled monolayer of 16
      phosphonohexadecanoic acid on the MoO, prior to spin-coating the PEDOT: PSS.
      Cells fabricated on PEDOT: PSS/SAMs/MAM multilayer electrodes showed a power
      conversion efficiency of 2.33%, comparable to that of ITO-based organic solar
      cells. The PEDOT: PSS/SAMs/MAM electrode was shown to be a promising replacement
      of ITO for use in low-cost optoelectronic devices.

PMID- 25942866
TI  - Preparation and capacitive property of graphene nanosheets prepared by using an
      electrostatic method.
AB  - Graphite oxide (GO) is promising precursor for a bulk production of graphene
      based materials due to easy preparation. Typically, exfoliation and reduction of
      GO have depended on either sonication process using chemical agents or heat
      treatment. In this study, we introduce a preparation of exfoliated and reduced GO
      powder by using an electrostatic method. GO precursor was changed into black
      fluffy reduced GO powder by simple electrostatic force. The micro-structural and
      electrochemical properties are investigated by scanning electron microscopy
      (SEM), transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET)
      measurement, and cyclic voltammetry (CV). The prepared nanocomposites showed the
      superior capacitive performance with good rate capability, large specific
      capacitance, and excellent cyclic performance. As-prepared powder showed specific
      surface area of 516 m2/g, higher than value (283 m2/g) of microwave assisted
      reduced GNS powder. Using the exfoliated graphite oxide, we studied
      electrochemical behaviors for an application of supercapacitor electrode.

PMID- 25942867
TI  - Synthesis of amorphous carbon materials for lithium secondary batteries.
AB  - A new and effective approach to enhance electrochemical properties of amorphous
      carbons is presented. Phosphorus-doped amorphous carbons have been prepared by
      incorporating a phosphorus compound into petroleum cokes and carbonizing them at
      850 degrees C for 1 h. It was observed that reversible capacity of amorphous
      carbons was greatly improved by incorporating a very small amount of phosphorus
      (around 1%), implying that extra lithium-storage-sites were created by phosphorus
      doping. In addition, the phosphorus-doped amorphous carbons showed outstanding
      rate capability (205 mA h/g at 5 C) and excellent capacity retention of about 90%
      after 50 cycles, comparable to that of undoped carbons. Very interestingly, a
      trade-off relation between capacity and cycle property, which is very common in
      electrode materials, was not found in the phosphorus-doped amorphous carbons.

PMID- 25942868
TI  - Development of anion-conducting ionomer binder solutions for electrodes of solid
      alkaline fuel cells.
AB  - For solid alkaline fuel cell applications, membrane-electrode assemblies (MEAs)
      should be prepared. Thus, in this study, anion-conducting ionomer binder was
      prepared for electrodes of MEAs. Specifically, we synthesized water soluble
      anionic binder solutions based on quaternized chitosan derivatives (QCDs) and
      cross-linked QCDs and prepared a novel electrode. The electrochemical and
      physicochemical properties of ionomer binder and electrode were investigated by
      FT-IR, NMR and ionic conductivity. The ionic conductivity of these cross-linked
      QCDs was 9.7 x 10(-3) S cm(-1) in deionized water at room temperature. The
      membrane electrode assemblies (MEAs) were prepared by a spray method and were
      investigated in terms of cyclic voltammetry, impedance and fuel cell performance.
      The MEA with the 35 wt% QCD ionomer showed the highest performance and confirmed
      the successful formation of ionomer binder at the electrode of the MEA by the on
      site crosslinking reaction.

PMID- 25942869
TI  - Sulfonated poly(ether sulfone)s containing pyridine moiety for PEMFC.
AB  - Sulfonated poly(ether sulfone)s with varied degree of sulfonation (DS) were
      prepared via post-sulfonation of synthesized pyridine based poly(ether sulfone)
      (PPES) using concentrated sulfuric acid as sulfonating agent. The DS was varied
      with different mole ratio of 4,4'-(2,2-diphenylethenylidene)diphenol, DHTPE in
      the polymer unit. PPES copolymers were synthesized by direct polycondensation of
      pyridine unit with bis-(4-fluorophenyl)-sulfone, 4, 4'-sulfonyldiphenol and
      DHTPE. The structure of the resulting PPES copolymer membranes with different
      sulfonated units were studied by 1H NMR spectroscopy and thermogravimetric
      analysis (TGA). Sorption experiments were conducted to observe the interaction of
      sulfonated polymer with water. The ion exchange capacity (IEC) and proton
      conductivity were evaluated according to the increase of DS. The water uptake
      (WU) of the resulting membranes was in the range of 17-58%, compared to that of
      Nafion 211 28%. The membranes provided proton conductivities of 65-95 mS/cm in
      contrast to 103 mS/cm of Nafion 211.

PMID- 25942870
TI  - Preparation and Properties of Polysulfone-poly(ethylene glycol) graft copolymer
      membrane.
AB  - In this study, Graft copolymers composed of PSf backbones and PEG side chains
      were synthesized to prepare gas separation membranes with enhancing permeability
      and selectivity on carbon dioxide separation. PSf-g-PEG copolymers were
      synthesized by two steps, chloromethylation and graft reactions. Grafted PEG
      segment of PSf was controlled by molecular weight of PEG. Thermal properties of
      prepared mebrane were studied by TGA and DSC. T(g) of the copolymers was
      decreased with increasing of molecular weight of PEG. Hydrophilicity of PSf-g-PEG
      copolymer membrane was measured using contact angle method, and PEG grafted
      polymers showed lower contact angles due to higher hydrophilicity. Gas permeation
      properties of CO2 and N2 gases through the membranes were measured using time-lag
      method. The permeability of CO2 was enhanced with PEG moiety contents and
      increasing of number of PEG segment. The selectivity of CO2/N2 was increased with
      introducing of PEG due to higher solubility with CO2 gas.

PMID- 25942871
TI  - Size control of surfactant vesicles made by a mixture of cationic surfactants and
      organic derivatives.
AB  - Spontaneous size-controllable vesicles that are prepared by a mixture of
      surfactants with different alkyl chain lengths (n-alkyltrimethylammonium bromide,
      C(n)TAB) and an organic derivative (5-methyl salicylic acid, 5mS) in aqueous
      solution have been investigated. When the organic derivative 5mS is mixed with
      the C(n)TAB surfactants in aqueous solution, the surfactant vesicles are
      spontaneously formed above a certain 5mS concentration. Small angle neutron
      scattering reveals that the core radius of surfactant vesicles is clearly
      increased from ca. 31 nm to ca. 97 nm with the alkyl chain length of surfactants
      while the bilayer thickness of the vesicles is nearly constant. The structure of
      surfactant vesicles maintains against temperature change ranging from 30 degrees
      C to 45 degrees C, showing no structural change. These results can provide
      thermally stable surfactant vesicles with various sizes and constant bilayer
      thickness that may possess a different permeability and may allow the surfactant
      vesicle to be used in gene or drug delivery for a variety of goods.

PMID- 25942872
TI  - Initial oxidation of gallium arsenide (001)-beta2(2 x 4) surface using density
      functional theory.
AB  - The initial oxidation of a gallium arsenide (001)-beta2(2 x 4) surface with an
      oxygen molecule was investigated using density functional theory. The oxygen
      molecule was adsorbed on the surface without any energy barrier. The dissociation
      of the oxygen molecule on the first arsenic layer had two dissociation paths; the
      inter-dimer and intra-dimer. The inter-dimer dissociation was the dominant
      dissociation path based on the energy barriers. The two dissociated oxygen atoms
      preferred breaking the arsenic-gallium back-bond to form arsenic-oxygen-gallium
      bonds. Our results are in good agreement with literature of the scanning
      tunneling microscope study.

PMID- 25942873
TI  - Top-down fabrication of 4H-SiC nano-channel field effect transistors.
AB  - 4H-SiC nano-channel field effect transistors (FETs) with various widths of 3 MUm
      50 nm have been fabricated by "top-down" approach using electron-beam lithography
      process. It has been demonstrated that the gate controllability of the SiC FETs
      is improved with decreasing channel width. In the fabricated devices the
      threshold voltage V(th) for the 50 nm-width nano-channel FETs shows a positive
      shift (DeltaV(th) = 1.4 V) with respect to that of the reference FETs. The on
      current degradation of the SiC nano-channel FETs is found to be 1.5 times lower
      than that of the reference FETs at elevated temperatures up to 450 K. This
      attributed to the improved heat dissipation of the nano-channel structure with a
      large surface to volume ratio.

PMID- 25942874
TI  - Development of inorganic and organic hybrid nanocoating based on carbon nanotubes
      for corrosion resistance.
AB  - In this study, we report the synthesis and characterization of novel hybrid
      nanocoating based on carbon nanotubes (CNTs) on anodized aluminum surfaces (AAO).
      The hybrid nanocoating was deposited by number of methods which include spray
      coating, spin coating and dip coating. The bonding of nanocoating with metal
      surface is an important parameter for successful modification of the metal
      surfaces. The improved adhesion of nanocoating on metal surfaces could be
      attributed to chemical bonding of sol-gel nanocoating with anodized surfaces. The
      nanocoated anodized aluminum surfaces showed superior adhesion and excellent
      anticorrosive properties. The nanocoated panels showed enhanced galvanic
      protection comparable to 80% of titanium metal as determined by galvanic
      corrosion measurements. It also showed higher thermal conductivities than
      stainless steel and bare anodized surfaces.

PMID- 25942875
TI  - Emission enhancement of InGaN/GaN light emitting diode by using Ag nanoparticles.
AB  - We have studied the effect of surface plasmon (SP) coupling to enhance emission
      efficiency of light emitting diode (LED) with multiple quantum wells (MQWs)
      structure by positioning Ag nanoparticles on the line-arrayed patterns. The line
      arrayed patterns were fabricated by photolithography and inductively coupled
      plasma reactive ion etching process. The Ag nanoparticles were formed by thermal
      annealing at 300 degrees C and 400 degrees C for 30 min for Ag films with
      thickness of 10 nm and 15 nm deposited on the patterned LED structures,
      respectively. The photoluminescence (PL) emission intensity of line-patterned LED
      with Ag nanoparticles was overall enhanced. According to the spectra of time
      resolved PL, carrier life times of line-patterned LED with and without Ag
      nanoparticles appeared about 0.47 and 5.47 ns, respectively.

PMID- 25942876
TI  - Phosphorescent white organic light-emitting diodes by electron transporting layer
      engineering.
AB  - The authors describe the fabrication of white organic light-emitting diodes
      (WOLEDs) with dual electron transporting layers (D-ETL) using 2,9-dimethyl-4,7
      diphenyl-1,10-phenanhroline/ 4,7-diphenyl-1,10-phenanthroline (BPhen) and bis-(2
      methyl-8-quinolinolate)-4-(phenylphenolato) aluminum/BPhen. Stepwise D-ETL easily
      transports electrons easily to the emitting layer and reduces the leakage of
      electrons. Therefore, WOLEDs with D-ETL show higher external quantum efficiency
      (EQE) when compared to a control WOLED with a single ETL device. The optimized
      WOLEDs showed a peak EQE of 13.0%, luminous efficiency of 27.4 cd/A, and
      Commission Internationale de L'Eclairage coordinates of (0.40, 0.39) at 1000
      cd/m2.

PMID- 25942877
TI  - Growth of Er3+/Yb3+ co-doped CaMoO4 thin film by a spray coating and its
      upconverting luminescence.
AB  - Polycrystalline Er3+/Yb3+ co-doped CaMoO4 (CaMoO4:Er3+/Yb3+) film was
      successfully fabricated by a spray coating method. Crystal structure, surface
      morphology and upconversion (UC) luminescent properties were investigated. Under
      980-nm excitation, CaMoO4:Er3+/Yb3+ film exhibited strong green UC emissions at
      530 and 550 nm (2H,11/2 --> 4S3/2 - 4I15/2) visible to the naked eye with a weak
      red emission near 660 nm (4F9/2 --> 4I15/2) corresponding to the intra 4f
      transitions of Er3+. A possible UC mechanism related to the pump-power dependence
      is discussed in detail.

PMID- 25942878
TI  - Evaluation of the bonding strength of dental zirconia with veneering porcelains.
AB  - The effect of thermo-cycling treatment on the bond strength and flexural strength
      of porcelain veneered zirconia was evaluated. After thermo-cycling treatment
      between 5 degrees C to 55 degrees C, porcelain-zirconia bond strength and
      zirconia flexural strength was not significantly affected. In the phase analyses
      using XRD after thermo-cycling treatment, both the experimental group and the
      control group showed only tetragonal phases. That is, the porcelain-zirconia bond
      strength and zirconia flexural strength were not affected by low temperature
      degradation. So low temperature aging treatment did not reduce the flexural
      strength and the effect of temperature applied to the aging treatment could
      beignorable.

PMID- 25942879
TI  - Fabrication of bioactive, antibacterial TiO2 nanotube surfaces, coated with
      magnetron sputtered Ag nanostructures for dental applications.
AB  - We investigated whether a silver coating on an anodic oxidized titania (TiO2)
      nanotube surface would be useful for preventing infections in dental implants. We
      used a magnetron sputtering process to deposit Ag nanoparticles onto a TiO2
      surface. We studied different sputtering input power densities and maintained
      other parameters constant. We used scanning electron microscopy, X-ray
      diffraction, and contact angle measurements to characterize the coated surfaces.
      Staphylococcus aureus was used to evaluate antibacterial activity. The X-ray
      diffraction analysis showed peaks that corresponded to metallic Ag, Ti, O, and
      biocompatible anatase phase TiO2 on the examined surfaces. The contact angles of
      the Ag nanoparticle-loaded surfaces were significantly lower at 2.5 W/cm2 input
      power under pulsed direct current mode compared to commercial, untreated Ti
      surfaces. In vitro antibacterial analysis indicated that a significantly reduced
      number of S. aureus were detected on an Ag nanoparticle-loaded TiO2 nanotube
      surface compared to control untreated surfaces. No cytotoxicity was noted, except
      in the group treated with 5 W/cm2 input power density, which was the highest
      input of power density we tested for the magnetron sputtering process. Overall,
      we concluded that it was feasible to create antibacterial Ag nanoparticle-loaded
      titanium nanotube surfaces with magnetron sputtering.

PMID- 25942880
TI  - Thermoelectric characteristics of the p-type (Bi, Sb)2Te3 nanocomposites
      processed with silicon nanodispersion.
AB  - The p-type (Bi0.2Sb0.8)2Te3 powders were mechanically alloyed and hot pressed at
      500 degrees C for 30 minutes with dispersion of Si nanopowders up to 3 vol%. The
      thermal conductivity of the (Bi0.2Sb0.8)2Te3 nanocomposite was substantially
      reduced with dispersion of 0.3-3 vol% Si nanopowders due to the enhanced phonon
      scattering. The maximum dimensionless figure-of-merit of 1.32 at 75 degrees C was
      obtained for the (Bi0.2Sb0.8)2Te3 nanocomposite dispersed with 1 vol% Si
      nanopowders, compared to 1.08 of the specimen without Si nanopowder dispersion.

PMID- 25942881
TI  - The effect of Mn on flame spray pyrolysis-made ZnO nanoparticles for flammable
      gases detection.
AB  - The application of Mn-loaded ZnO nanoparticles to the design of flammable gas
      sensors is nowadays one of the most active research fields, due to their high
      activity, good adsorption characteristics and high selectivity with high response
      to toxic and combustible gases. It is sensitive to many gases at moderate
      temperature, such as C2H4, CH4 and C2H2 gases. FSP presents a new technique for
      0.25-1.00 mol% Mn-loaded ZnO nanoparticles synthesis which involves only a single
      step. The crystallite sizes of ZnO spherical and hexagonal particles were found
      to be ranging from 5 to 15 nm while ZnO nanorods were seen to be 5-15 nm in width
      and 20-40 nm in length. In addition, very fine Mn nanoparticles were uniformly
      deposited on the surface of ZnO particles. The highest response for CH4 gas was 
      240 towards 0.50 mol% Mn-loaded ZnO at 1.0 vol.% concentration of CH4 in dry air
      at 300 degrees C. The response of 0.50 mol% Mn-loaded ZnO of C2H4 gas was as high
      as 72 for 1.0 vol.% while the response for C2H2 gas was -13 towards 0.50 mol% Mn
      loaded ZnO at 1.0 vol.% concentration of C2H2 in dry air at 300 degrees C.

PMID- 25942882
TI  - Defect-induced ferromagnetism of mechanical-milled BaTi0.98Mn0.02O3
      nanoparticles.
AB  - Room-temperature ferromagnetism was found in BaTi0.98Mn0.02O3 nanoparticles
      fabricated by solid-state reaction and mechanical-ball milling. The nature of
      ferromagnetism was systematically investigated by means of X-ray diffraction
      (XRD), electron spin resonance (ESR), superconducting quantum interference device
      (SQUID), and X-ray absorption (XAS). A weak ferromagnetism was found in the
      defect-rich samples with the milling time (t(m)) longer than 6 hrs (i.e., t(m) >
      6 hrs), while defect-poor ones with t(m) = 0-6 hrs exhibited mainly the
      paramagnetic properties. Detailed analyses of ESR and XAFS data indicated the
      shift in the oxidation state of Mn from 4+ to 3+ after milling, and both Mn3+ and
      Mn4+ were incorporated into the Ti sites of the BaTiO3-tetragonal host lattice.
      With the results obtained, we believe that exchange interactions due to Mn(4+)
      Mn4+ and/or Mn(3+)-Mn3+ dipole pairs are responsible for broad ESR signals in the
      Lorentzian shape and the paramagnetic behaviors of the samples. Meanwhile, the
      weak ferromagnetic interaction is generated from various point defects such as Ti
      site cation vacancies or Ti(3+)-Ti3+ super-exchange interaction pairs.

PMID- 25942883
TI  - Photocurable, solventless, solution-processable, silica-nanoparticle-dispersed
      acryl hybrid materials.
AB  - Solventless silica-acryl hybrid materials composed of organically modified silica
      nanoparticles and acryl monomers were fabricated using a simple sol-gel process
      and solvent evaporation. The homogeneously dispersed silica-acryl hybrid
      materials can be formed into films through a simple solution-coating process and
      UV curing. The silica-acryl hybrid materials exhibited good photocurability with 
      90% conversion upon UV exposure and a high transmittance of above 95% in the
      visible wavelength region regardless of the silica nanoparticle content. In
      particular, the silica-acryl hybrid materials exhibited increased mechanical
      hardness and thermal stability directly proportional to the content of silica
      nanoparticles and exhibited a good surface roughness of -1 nm. Therefore, these
      silica-acryl hybrid materials are good candidates for coating applications in
      electronic, electro-optic, and energy devices.

PMID- 25942884
TI  - Effects of cementation factors on the Cu nanoparticle deposit of Cu-multi-wall
      carbon nanotubes composites.
AB  - Copper (Cu) coated carbon nanotubes (CNTs) were prepared and investigated by
      chemical reduction or cementation method. The morphology changes of Cu
      nanoparticles deposited onto the multiwall carbon nanotubes with metallic zinc
      (Zn) as a reducing agent have been examined at different cementation factors. The
      precipitated Cu nanoparticles from the copper ion in the reaction solution were
      deposited onto and entangled with the CNT substrates. CNTs used were multi-wall
      carbon nanotubes with average diameter of 10-20 nm and length of 10-50 MUm. As
      prepared CNTs products were purified by nitric acid solution, and then the CNTs
      were washed several times with distilled water, and dried in vacuum. The pre
      treated CNTs were suspended in solvent. Then, the copper salt was dissolved in
      the suspension containing the CNTs. The deposited morphology and distribution of
      copper particles on the CNTs substrate were investigated by changing the solute,
      solvent and reducing agent. The Cu/CNTs agglomerates were obtained in the
      presence of copper chloride and copper sulphate salts, and water and ethanol were
      used as the solvents. And the raw CNTs were pretreated with glacial acetic acid
      for increasing the coverage rate of copper particles over the CNTs surface at
      different acid concentrations. The Cu deposited CNTs were characterized in
      respect of morphology and distribution of CNTs and Cu particles with field
      emission scanning electron microscopy (FESEM). The copper crystals were
      identified by X-ray diffraction patterns.

PMID- 25942885
TI  - Uniform evolution of nanoporosity on amorphous Ti-Cu alloys.
AB  - Amorphous binary Ti(100-x)Cu(x) (x = 40, 50 and 60 at%) alloys, as the starting
      materials, were dealloyed in 0.03 and 0.13 M HF solutions under a free immersion
      condition, and a uniform nanoporous structure with a pore size of 71-220 nm and
      ligament size of 72-209 nm was obtained after immersion for 43.2 ks. The
      evolution of nanoporosity underwent more uniformly due to the absence of the
      intermetallics and defects such as grain boundary, segregation in the chemical
      composition in the amorphous precursors. The pore size and the ligament size
      increased with the immersion times and the concentration of the treatment
      solutions. The pore size increased with the dealloying times exponentially with
      an exponent of 0.41-0.79. The evolution of nanoporosity was influenced by the
      alloy compositions, and the formation of the ligaments was controlled by surface
      diffusion of the Cu adatoms, and also influenced by the coverage of noble Cu
      contents in Ti-Cu alloys.

PMID- 25942886
TI  - Synthesis and characterization of SiC nanocomposite catalyst supports with self
      formed nanowires.
AB  - Nickel-loaded SiC-alumina structural catalysts containing nanowires were facilely
      fabricated via modified sol-gel process mediated by supercritical carbon dioxide,
      followed by thermal-treatment. The nanowires were formed by metal-catalyzed
      growth on the outer and inner parts of SiC-alumina nanocomposite beads containing
      more than 3 wt.% of the metal seed at a moderate temperature of 1,100 degrees C
      under nitrogen gas flow. Highly dispersed Ni active catalysts were deposited on
      the surface of the nanowires formed outer and inner parts of the bead catalyst
      supports through the catalyst pretreatment process in the supercritical carbon
      dioxide. As a result, a new Ni/SiC heterogeneous catalyst with an enhanced
      surface area was successfully prepared using the SiC-alumina catalyst supports
      with a nanowire structure.

PMID- 25942887
TI  - Study on particle distribution in A356/SiCp upward suction castings.
AB  - In this investigation, cylindrical A356-5%50 MUm SiCp and A356-10%100 MUm SiCp
      castings of 40 mm diameter and 350 mm height were produced by stirring
      preparation and vertically upward suction casting process. The SiCp fractions in
      the casting different sections along the filling direction were quantitatively
      measured. The composite slurry flow during the casting mold filling was simulated
      based on the Euler method while the particle flow was calculated with the
      Lagrangian method for predicting the SiCp distribution. The simulated
      distributions were compared and validated with the experiment. It has shown that
      as the filling distance increased, the particle fractions decreased dramatically
      in the A356-10%100 MUm SiCp casting while varied slightly in the A356-5%50 MUm
      SiCp casting, and that the particles were prone to be aggregated near the mold
      wall at the filling beginning parts whereas more particles concentrated in the
      centre and fewer particles were present near the wall region in the casting
      front.

PMID- 25942888
TI  - Thermoelastic characteristics of thermal barrier coatings with layer thickness
      and edge conditions through mathematical analysis.
AB  - The thermoelastic behaviors of such as temperature distribution, displacements,
      and stresses in thermal barrier coatings (TBCs) are seriously influenced by top
      coat thickness and edge conditions, which were investigated based on the thermal
      and mechanical properties of plasma-sprayed TBCs. A couple of governing partial
      differential equations were derived based on the thermoelastic theory. Since the
      governing equations are too involved to solve analytically, a finite volume
      method was developed to obtain approximations. The thermoelastic characteristics
      of TBCs with the various thicknesses and microstructures were estimated through
      mathematical approaches with different edge conditions. The results demonstrated
      that the top coat thickness and the edge condition in theoretical analysis are
      crucial factors to be considered in controlling the thermoelastic characteristics
      of plasma-sprayed TBCs.

PMID- 25942889
TI  - Synthesis of Li2MnSiO4-graphene composite and its electrochemical performances as
      a cathode material for lithium ion batteries.
AB  - The Li2MnSiO4 is a promising candidate as a cathode for lithium ion batteries due
      to its large theoretical capacity of 330 mA h g(-1) and high thermal stability.
      However, the problems related to low electronic conductivity and large
      irreversible capacity at the first cycle limits its practical use as a Li-ion
      cathode material. We have developed a carbon coated Li2MnSiO4-graphene composite
      electrode to overcome these problems. Our designed electrode exhibits high
      reversible capacity of 301 mA h g(-1), with a high initial coulombic efficiency,
      and a discharge capacity at current rate of 0.5 C, that is double value of carbon
      coated Li2MnSiO4-carbon black composite electrode. These significant improvements
      are attributed to fast electron transport along the graphene sheet.

PMID- 25942890
TI  - Enhanced water splitting stability with controlled NiO co-catalyst on GaN
      photoanode.
AB  - Arrayed NiO co-catalyst on GaN is proposed to improve water splitting efficiency
      and to obtain stable photoelectrolysis without dissolution of photoanode. The
      characteristics of photoanodes were investigated by changing the height of NiO on
      n-GaN. The photoanode stability and performance of GaN with NiO was significantly
      improved compared to the reference GaN at zero bias. SEM measurements showed
      negligible etching of NiO and GaN surfaces, which confirmed considerably improved
      stability compared to the reference n-GaN. In summary, enhanced water splitting
      efficiency and photoanode stability were achieved by combining GaN with NiO co
      catalyst which are advantageous for water splitting applications.

PMID- 25942891
TI  - Using the hydrothermal method to grow p-type ZnO nanowires on Al-doped ZnO thin
      film to fabricate a homojunction diode.
AB  - In this study, the hydrothermal method is used to grow phosphorus-doped ZnO
      nanowires on Si/SiO2 substrates deposited with Al-doped ZnO thin film. This
      structure forms a homogeneous p-n junction. In this study, we are the pioneers to
      use ammonium hypophosphite (NH4H2PO2) as a source of phosphorus to prepare the
      precursor solution. Ammonium hypophosphite of different concentration levels is
      used to observe its effects on the growth of nanowires. The results show that the
      precursor solution prepared from ammonium hypophosphite can produce good
      crystalline ZnO nanowires while there is no linear relationship between the
      amounts and concentration levels of phosphorus doped into the nanowires. Whether
      the phosphorus-doped ZnO nanowires have the characteristics of a p-type
      semiconductor is indirectly verified by measuring whether the p-n junction made
      up of Al-doped ZnO thin film and phosphorus-doped ZnO nanowires shows rectifying
      behavior. I-V measurements are made on the specimens. The results show good
      rectifying behavior, proving that the phosphorus-doped ZnO nanowires and Al-doped
      AZO films have p-type and n-type semiconductor properties, constituting a good p
      n junction. This result also proves that ammonium hypophosphite is a better
      source of phosphorus in the hydrothermal method to synthesize phosphorus-doped
      ZnO nanowires.

PMID- 25942892
TI  - Electric-field-induced spin injection enhancement.
AB  - The spin diffusion process can be modified by the electric field in a
      semiconductor channel. The electric field generated by the bias current improves
      the spin injection efficiency as well as the spin diffusion length at a
      ferromagnet-semiconductor hybrid system. Spin-polarized electrons from the
      ferromagnetic electrode were electrically investigated in an inverted
      heterostructure with an In0.53Ga0.47As active layer. Using local and non-local
      spin valve geometries, the interfacial spin polarizations with and without an
      electric field are extracted from the magnitude of spin transport signals. The
      interfacial spin polarization is increased from 3.2% to 7.0% with a current of 1
      mA at T = 20 K. When the electric field assists the spin injection at the
      junction, the interfacial spin polarization remains 7% at the temperature ranged
      from 20 K to 200 K. Temperature dependence of the injected polarization shows
      that the electric field can compensate the thermal smearing of injection
      efficiency even at higher temperature.

PMID- 25942893
TI  - Fe-Si-Cr/PTFE magnetic composite thick films on polyethylene terephthalate sheets
      for near field communications by aerosol deposition.
AB  - Thick film growth of Fe-Si-Cr/poly-tetra-fluoro-ethylene (PTFE) composite films
      on polyethylene terephthalate (PET) sheets was investigated by aerosol deposition
      (AD) as a magnetic absorber for near field communication. The Fe-Si-Cr flakes
      were crushed to micro flakes smaller than 1 MUm after the deposition, and formed
      dense microstructure on the PET sheets. The Fe-Si-Cr/PTFE composite thick films
      using 0.2 wt.% PTFE starting powder showed dense and uniform microstructure
      compared to the 0.5 wt.% film. The real relative permeability /' and the
      imaginary permeability MU" of Fe-Si-Cr/PTFE composite thick films using the 0.2
      wt.% PTFE starting powder were 13.1 and 2.9 at 13.56 MHz, respectively. In the
      case of 0.5 wt.%, MU' and MU" respectively decreased to 7.4 and 1.0 at 13.56 MHz
      caused by adding PTFE.

PMID- 25942894
TI  - Synthesis of the thermoelectric nanopowder recovered from the used thermoelectric
      modules.
AB  - We fabricated the thermoelectric powder using the used thermoelectric modules in
      a vehicle. As a starting material, the used thermoelectric modules were collected
      and separated to substrate, electrode, solder, and thermoelectric parts by a
      thermal process. The separation process was performed in a wet process at the
      critical temperature. The solder in the module was the neighbor part of the
      thermoelectric material with the lowest melting temperature in the module. We
      focused on the thermal property of the solder to separate the thermoelectric
      chips in the module. After the separation process, we prepared the pure
      thermoelectric material by the chemical etching for an impurity removal. Also the
      thermoelectric nanopowder was fabricated by a chemical reduction reaction using
      the recycled thermoelectric materials. The recovered nanopowder was confirmed to
      the phase of bismuth telluride (Bi2Te3) with the particle size of -15 nm.

PMID- 25942895
TI  - Magnetic nanodiscs fabricated from multilayered nanowires.
AB  - We report a simple, high throughput synthesis method of producing magnetic
      nanodiscs, in which the diameter and thickness are easily controlled. This method
      consists of two steps: (1) Electrodeposition for growing multilayered nanowires
      and (2) Selective etching of sacrificial layers. The electrodeposition step
      results in a bundle of multilayered nanowires. The nanowires consist of
      alternating layers of magnetic (e.g., Co) and sacrificial materials (e.g., Cu)
      inside the nanometer-sized pores of an anodized aluminum oxide (AAO) template.
      The diameter of each layer is determined by pore size, while the thickness is
      controlled by electrodeposition time. The selective wet etching step removes
      sacrificial layers, leaving the magnetic nanodiscs. Through this process, the
      magnetic nanodiscs are fabricated with aspect ratios ranging from 0.25 to 2.0.

PMID- 25942896
TI  - Mechanical properties and microstructure of AZ31 Mg alloy containing Ca element
      fabricated by various rolling speeds.
AB  - It was reported that the yield strength (YS) of a rolled Mg-3 wt%, Al-1 wt%, Zn
      0.3 wt%, Ca alloy reached 340 MPa. The YS value of a rolled Mg-Al-Zn alloy
      decreases with increasing the rolling speed but that of a rolled Mg-Al-Zn-Ca
      alloy remains unchanged until the rolling speed of 5 m/min. Static
      recrystallization behavior in Mg-Al-Zn alloy occurred as a function of rolling
      speeds; on the other hand, it did not happen in Mg-Al-Zn-Ca alloy. A number of
      fine precipitates were observed in the grain of the latter alloy, suggesting that
      they restrain the dislocations from moving during rolling processes and keep the
      high strength. From the result of boss-forming test, the Mg-Al-Zn-Ca alloy shows
      more boss-formability than Mg-Al-Zn alloy.

PMID- 25942897
TI  - Thermal conductivities of nanostructured magnesium oxide coatings deposited on
      magnesium alloys by plasma electrolytic oxidation.
AB  - The resistances of magnesium alloys to wear, friction and corrosion can be
      effectively improved by depositing coatings on their surfaces. However, the
      coatings can also reduce the heat transfer from the coated components to the
      surroundings (e.g., coated cylinder bores for internal combustion of engine
      blocks). In this paper, nanostructured magnesium oxides were produced by plasma
      electrolytic oxidation (PEO) process on the magnesium alloy AJ62 under different
      current densities. The guarded comparative heat flow method was adopted to
      measure the thermal conductivities of such coatings which possess gradient
      nanoscale grain sizes. The aim of the paper is to explore how the current density
      in the PEO process affects the thermal conductivity of the nanostructured
      magnesium coatings. The experimental results show that, as the current density
      rises from 4 to 20 A/mm2, the thermal conductivity has a slight increase from
      0.94 to 1.21 W/m x K, which is significantly smaller than that of the
      corresponding bulk magnesium oxide materials (29.4 W/m x K). This mostly
      attributed to the variation of the nanoscale grain sizes of the PEO coatings.

PMID- 25942898
TI  - Molecular design and photovoltaic performance of organic dyes containing
      phenothiazine for dye-sensitized solar cells.
AB  - We synthesized novel organic photosensitizers based on fluorine-substituted
      phenothiazine with thiophene bridge units in the chromophore for application in
      dye-sensitized solar cells (DSSCs). Furthermore, organic dyes with different
      acceptors exhibited higher molar extinction coefficients, and better light
      absorption at longer wavelengths. The photovoltaic properties of organic dyes
      composed of different acceptors in their chromophores were measured to identify
      their effects on the DSSC performance. The organic dye, PFSCN2 containing multi
      cyanoacrylic acid as the electron acceptor, showed a power conversion efficiency
      of 4.67% under AM 1.5 illumination (100 mW/cm2). The retarded recombination
      kinetics from TiO2 electrode to electrolyte enhanced the electron life time of
      the organic dye, PFSCN2 in the photoanode of the DSSC. This was confirmed with
      impedance analysis.

PMID- 25942899
TI  - Electrochemical properties of the NiS powder prepared by co-precipitation method
      for lithium secondary battery.
AB  - We synthesized two nickel sulfide powders by simple method. One is nickel sulfide
      powder (CNS) by co-precipitation is composed of nano-sized nickel sulfides as NiS
      and NIS2. The other is nickel sulfide powder (HNS) by heat-treatment of CNS is
      composed nano-sized NIS. The electrode using CNS has a high first discharge
      capacity of 600 mA h g(-1) at 0.5 C and the discharge capacity after 20th cycle
      is 312 mA h g(-1). The electrode using HNS has a high first discharge capacity of
      551 mA h g(-1) at 0.5 C and has the discharge capacity of 412 mA h g(-1) after
      50th. The discharge rate capability has over 92% at 1 C versus 0.2 C. The nano
      sized nickel sulfides are synthesized by simple co-precipitation method has good
      electrochemical properties such as high first discharge capacity, good cycle life
      and good rate capability for lithium secondary battery.

PMID- 25942900
TI  - Synthesis and characterization of sulfonated poly(ether sulfone)s containing
      mesonaphthobifluorene for polymer electrolyte membrane fuel cell.
AB  - The novel sulfonated poly(ether sulfone)s containing mesonaphthobifluorene (MNF)
      moiety were synthesized and characterized their properties. The prepared polymers
      have highly conjugated aromatic structure due to the MNF group which is an
      allotrope of carbon and one atom thick planar sheets of sp2-bonded carbon atoms.
      Poly(ether sulfone)s bearing tetraphenylethylene on polymer backbone were
      synthesized by polycondensation and followed intra-cyclization from
      tetraphenylethylene to form MNF by Friedel-craft reaction with Lewis acid
      (FeCl3). The sulfonation was performed selectively on MNF units with conc.
      sulfuric acid. The structural properties of the sulfonated polymers were
      investigated by 1H-NMR spectroscopy. The membranes were studied by ion exchange
      capacity (IEC), water uptake, and proton conductivity. The synthesized polymer
      electrolyte membranes showed better thermal and dimensional stabilities owing to
      the inducted highly conjugated aromatic structure in the polymer backbone. The
      water uptake of the synthesized membranes ranged from 23-52%, compared with
      32.13% for Nafion 211 at 80 degrees C. The synthesized membranes exhibited proton
      conductivities (80 degrees C, RH 90%) of 74.6-100.4 mS/cm, compared with 102.7
      mS/cm for Nafion 211.

PMID- 25942901
TI  - Initial surface reaction of di-lsopropylaminosilane on a fully hydroxyl
      terminated Si (001) surface.
AB  - We studied the interaction of di-isopropylaminosilane (SiH3N(C3H7)2, DIPAS)
      molecules with a fully hydroxyl-terminated Si (001) surface for SiO2 thin-film
      growth by using density functional theory. The amino group consisting of DIPAS
      was chosen in order to obtain a high adsorption energy because its lone-pair
      electrons in the N atom would help in the adsorption of DIPAS. The absolute value
      of the adsorption energy (0.67 eV) of DIPAS was higher than its reaction energy
      barrier of 0.38 eV. Thus, DIPAS could react with the surface without desorption.
      The reaction between DIPAS and the surface produced a silyl group (-SiH3) as a
      primary product and di-isopropylamine (NH(C3H7)2, DIPA) as a by-product. A second
      DIPAS, which was adsorbed near the pre-adsorbed DIPAS or -SiH3 with DIPA,
      required higher reaction energy barriers of 3.91 or 1.92 eV, respectively,
      because of its interaction with the first DIPAS or DIPA. However, when the second
      DIPAS was adsorbed near -SiH3 without DIPA, a low reaction energy barrier of 0.42
      eV was required, indicating a negligible effect of -SiH3 on the second DIPAS
      reaction. Therefore, to obtain a highly dense Si layer, DIPA must desorb from the
      surface. DIPA requires a relatively high desorption energy of 0.40 eV because the
      lone-pair electrons in the N atom of DIPA also enhance its adsorption on the
      surface. The high desorption energy could reduce the process window of atomic
      layer deposition.

PMID- 25942902
TI  - Transmission electron microscopy study of 3.2 YSZ single crystals manufactured by
      the skull melting method.
AB  - Transmission electron microscopy (TEM) analyses were performed to examine the
      spontaneously ordered structure in single crystals of 3.2 mole% of Y2O3 added
      ZrO2 (3.2 YSZ) manufactured by the Skull melting method. The selected area
      electron diffraction patterns showed several super-structure reflections with
      symmetrical intensity at (100), (010), and (110) positions, indicating that
      Y0.5Zr0.5O(2-x) with L1(0)-like cation-ordered structure was formed in 3.2 YSZ.
      High-resolution TEM has been used to reveal the presence of the partially ordered
      structure, which was characterized by a doublet periodicity in the contrast of
      the {100} lattice planes.

PMID- 25942903
TI  - Characterization of protein-immobilized polystyrene nanoparticles using impedance
      spectroscopy.
AB  - A novel approach for characterization of non-conductive protein-immobilized
      nanoparticles using AC impedance spectroscopy combined with conductive atomic
      force microscopy was examined. As AC impedance spectroscopy can provide
      information on diverse electrical properties such as capacitance and inductance,
      it is applicable to the characterization of non-conductive substances. Several
      non-conductive protein-immobilized polystyrene nanoparticles were analyzed using
      AC impedance spectroscopy, and their impedance spectra were used as markers for
      nanoparticle identification. Analyses of impedance signals using an electrical
      circuit model established that the capacitance and inductance of each
      nanoparticle changed with the adsorbed protein and that impedance spectral
      differences were characteristic properties of the proteins. From this study, AC
      impedance spectroscopy was shown to be a useful tool for characterization of non
      conductive nanoparticles and is expected to be applicable to the development of
      sensors for nanomaterials.

PMID- 25942904
TI  - Nanocrystalline ZnO thin film deposition on flexible substrate by low-temperature
      sputtering process for plastic displays.
AB  - A low temperature sputter deposition process is adopted to fabricate
      nanocrystalline ZnO thin films on plastic (polyethylene terepthalate) substrate.
      Very good crystalline films are synthesized at a substrate temperature around 120
      degrees C. Structural and microstructural analyses confirm the proper phase
      formation of the nanomaterial with an average nanoparticle size around 5-10 nm.
      Optical transmission analysis of the film deposited on plastic substrate depicts
      nearly 90% visible transmittance with a direct bandgap around 3.56 eV. This cost
      effective, low-temperature fabrication of nanocrystalline thin film with very
      good structural and optical properties will find important applications in
      plastic display technology. Also the process is a vacuum-based clean process,
      which is compatible to CMOS-IC fabrication techniques and therefore, can easily
      be integrated with modern solid state device fabrication processes for diverse
      device applications.

PMID- 25942905
TI  - Synthesis and chemosensing properties of indole based donor- Pi-acceptor dye
      material.
AB  - In this work, we have designed and synthesized a new chemosensor for the
      detection of various metal ions. The chemosensor named 2-[2-(1 H-indole-2
      ylmethylene)-3-oxo-indan-1-yliden]- malononitrile was synthesized using 3-formyl
      indole and 2-(3-oxo-indan-1-yliden)-malononitrile. This chemosensor has been
      investigated the properties which are able to detect and recognize the detection
      function of heavy metal ions. D-pi-A system of dye chemosensor between electron
      withdrawing malononitrile and electron donating indole moieties provides the
      functions to interact with target metal ions. These recognizing sensing effects
      were studied using the absorption behaviors. Furthermore, cyclic voltammogram was
      used to determine HOMO/LUMO energy levels from their redox onset points. Measured
      energy levels of HOMO/LUMO were compared with computational calculation and
      discussed in details. Finally, the interaction type of metal ions binding was
      determined by Job's plot measurements.

PMID- 25942906
TI  - Microstructure and properties of cross-roll rolled and heat treated metastable
      TiNbSn alloy.
AB  - A (Ti-35mass%Nb)-4mass%Sn alloy was cross-roll rolled with a reduction ratio of
      70% in which the roll axes are tilted by +/- 5 degrees away from the transverse
      direction of the rolled sample and then aged at 250 degrees C for 2 h. Cross-roll
      rolling was found to increase yield strength and Young's modulus, simultaneously.
      Yield strength was higher in cross-roll rolled than in conventionally rolled at
      same reduction ratio. Yield and tensile strength further increased by a low
      temperature ageing by psi precipitation hardening and microstructure refinement.
      Yield and tensile strength of the aged 70% cross-roll rolled sample were higher
      than those of the aged 70% conventionally rolled one.

PMID- 25942907
TI  - Patterned growth of Au nanoparticles on polycrystalline lead zirconate titanate
      surfaces.
AB  - We report the patterned growth of Au nanoparticles (NPs) on polarity-patterned
      polycrystalline lead zirconate titanate (PZT) as a template through photochemical
      reaction. The photochemical deposition of the Au NPs includes ultraviolet (UV)
      light illumination of the patterned PZT while immersed in a HAuCl4 solution. In
      particular, the influence of the UV wavelength, and the influence of the solution
      with the stabilizer and reducer on the growth selectivity of the Au NPs on the
      polarity-patterned regions was investigated. For a UV light of 365 nm wavelength,
      corresponding to a band-gap excitation of the PZT, more Au NPs were deposited on
      the + z polar region than on the other non-polar regions. However, no deposition
      of the Au NPs was observed for UV light wave-lengths longer than - 365 nm. When
      ascorbic acid (AA) as a reducer and cetyl-trimethylammonium bromide (CTAB) as a
      stabilizer were added to the HAuCl4 solution, the Au NPs on the + z polar region
      were observed to be deposited with a UV light of 435 nm, which is larger than the
      optical band gap wavelength of the PZT. Also, the growth selectivity and size
      uniformity on the + z region was significantly improved. These results could be
      due to the defect-induced photo-excitation of electrons and enhanced reduction
      process of Au+ ions by adding the reducer and the stabilizer in the photo
      chemical process. This study suggests the possibility of the patterned growth of
      Au NPs on a ferroelectric surface through polarity patterning and photochemical
      reaction by optimizing the UV wavelength and employing reduction potential agents
      in a metal salt solution.

PMID- 25942908
TI  - Preparation of Janus silica particles with organo-silane compounds using
      polystyrene trapping layer.
AB  - In this study, the Janus silica particles were prepared by grafting reaction
      based on the sol-gel method. Before the surface modification reaction, the silica
      particles were trapped in the PS layer and some fraction of their surface were
      only reacted with APTES. XPS analysis confirmed that the nitrogen compounds were
      introduced on the surface of the Janus particles, and the curve fitting of
      nitrogen confirmed that the compounds were the amine groups. From the result of
      SEM analysis, there were no differences in the size and the surface morphology
      and no formation of the APTES clusters. Based on these results, it was confirmed
      that the Janus silica particles were prepared using PS trapping layer.

PMID- 25942909
TI  - Preparation of magnetite hollow structure for drug delivery application.
AB  - Monodispersed Fe3O4 nanospheres with hollow interior and porous shell structures
      were synthesized without any template by refluxing iron precursor solution in a
      Teflon-line autoclave at 200 degrees C. Those nanoparticles exhibited a
      ferromagnetic behavior with a high saturation magnetization of 76 emu/g. The
      hollow structure was formed based on the assembly of many small particles to form
      large-sized spheres, followed by chemical conversion coupled with Oswald ripening
      process. Due to the differences in size, density and/or crystallinity between the
      outer and interior particles in the spheres, the inner particles migrated to the
      outer shell, resulting in the formation of the empty space inside nanostructures.
      The potential application of Fe3O4 hollow nanoparticles as a drug carrier was
      evaluated with Rhodamine6G as a model drug, showing a pH-dependent release
      profile due to the difference of proton concentration.

PMID- 25942910
TI  - In-situ molybdenum nano-attached particle synthesis from spent Mo scrap.
AB  - Radio frequency thermal plasma is a versatile process for engineering powder
      preparation owing to its high energy density and reactivity. Molybdenum powders
      were prepared from molybdenum sheet scrap by RF thermal plasma in association
      with powder comminution process. Molybdenum scrap which was used in high
      temperature environment was friable enough to be broken into micropowders by
      hammer milling. Spherical molybdenum micro-powder was obtained from the hammer
      milled powders were treated via thermal plasma. On the other hand, vaporization
      and condensation pathway for nanoparticle synthesis is largely dependent on both
      thermo-physical properties and thermal plasma properties. In this regard,
      molybdenum trioxide was chosen for the feedstock of nanoparticle synthesis.
      Additional reactivity of argon-hydrogen thermal plasma, oxide feedstock was fully
      reduced to bcc molybdenum. Considering different reaction pathway of each
      feedstock, molybdenum nanoparticle attached molybdenum spherical micro-powder
      could be effectively synthesized by feeding a blended feedstock of molybdenum
      micro-powder and molybdenum trioxide micro-powder into argon-hydrogen thermal
      plasma.

PMID- 25942911
TI  - Effect of calcination temperature on the photocatalytic properties of electrospun
      TiO2 nanofibers.
AB  - In this study, TiO2 nanofibers with a high aspect ratio and a large specific
      surface area were synthesized using the electrospinning technique, and the effect
      of calcination temperature on their crystal structure, diameter, specific surface
      area and photocatalytic activity was systematically investigated. The
      electrospun, as-prepared PVP/TTIP nanofibers were several tens of micrometers in
      length with a diameter of 74 nm. TiO2 nanofibers with an average diameter of 50
      nm were prepared after calcination at various temperatures. The calcination
      temperature significantly influenced the photocatalytic and material properties
      of TiO2 including grain size and specific surface area. When compared to other
      nanostructured TiO2 materials, such as commercial TiO2 nanoparticles (P25,
      Degussa), the TiO2 nanofibers exhibited greater photocatalytic activity for the
      degradation of acetaldehyde and ammonia.

PMID- 25942912
TI  - Filler effect of ionic liquid attached titanium oxide on conducting property of
      poly(ethylene oxide)/poly(methyl methacrylate) composite electrolytes.
AB  - Composite polymer electrolytes (CPEs) were prepared by containing blend of
      poly(ethylene oxide) (PEO) and poly(methyl methacrylate) (PMMA) as a host
      polymer, propylene carbonate as a plasticizer, and LiClO4 as a salt. By an
      addition of a various content of ionic liquid attached TiO2 (IL-TiO2) to above
      electrolytes, the effects were studied. As a result, by increasing the IL-TiO2
      content, the crystallinity of PEO was decreased and the ionic conductivity was
      increased. The ionic conductivity of CPEs was dependent on the content of IL-TiO2
      and showed the highest value of 1.05 x 10(-4) S/cm at 9 wt.%. However, when IL
      TiO2 content exceeds 9 wt.%, the ionic conductivity was decreased due to the slow
      ionic transport due to immiscibility or aggregation of the IL-TiO2 filler within
      the polymer film matrix.

PMID- 25942913
TI  - Microstructure and mechanical properties of ultrafine grained complex copper
      alloy fabricated by accumulative roll-bonding process.
AB  - Accumulative roll-bonding (ARB) process using dissimilar copper alloys was
      performed up to six cycles (-an equivalent strain of 4.8) at ambient temperature
      without lubricant for fabrication of a new complex copper alloy. The dissimilar
      copper alloy sheets of oxygen free copper (OFC) and dioxide low-phosphorous
      copper (DLPC) with thickness of 1 mm were degreased and wire-brushed for the ARB
      process. The sheets were then stacked together and rolled by 50% reduction so
      that the thickness became 1 mm again. The sheet was then cut to the two pieces of
      same length and the same procedure was repeated up to six cycles. A new sound
      complex copper alloy sheet in which OFC and DLPC are combined each other was
      successfully fabricated by the ARB process. The tensile strength of the copper
      alloy increased with increasing the number of ARB cycles, reached 492 MPa after
      six cycles, which is about three times of the initial material. The average grain
      size was 12.6 MUm after the 1st cycle, but it became 1.5 MUm after six cycles.
      Microstructures and mechanical properties of the complex copper alloy fabricated
      by the ARB were investigated in detail.

PMID- 25942914
TI  - Evaluation of damage models by finite element prediction of fracture in
      cylindrical tensile test.
AB  - In this research, tensile tests of cylindrical specimens of a mild steel are
      predicted via the finite element method, with emphasis on the fracture
      predictions of various damage models. An analytical model is introduced for this
      purpose. An iterative material identification procedure is used to obtain the
      flow stress, making it possible to exactly predict a tensile test up to the
      fracture point, in the engineering sense. A node-splitting technique is used to
      generate the cracks on the damaged elements. The damage models of McClintock,
      Rice-Tracey, Cockcroft-Latham, Freudenthal, Brozzo et al. and Oyane et al. are
      evaluated by comparing their predictions from the tensile test perspective.

PMID- 25942915
TI  - Surface oxidation behaviors of Cd-rich CdSe quantum dot phosphors at high
      temperature.
AB  - The optical properties of quantum dots (QDs) are altered by exposure to air and
      light; upon such exposure, the quantum yield is typically reduced. Improved
      understanding of surface oxidation and oxide-layer behavior, both of which
      influence the photoluminescence of QDs, is necessary for advancing the use of
      QDs. In this study, the oxide layer properties of QDs are investigated. The QDs
      are synthesized and subsequently oxidized by heat treatment in atmospheric
      conditions, and the luminescence properties of the resultant QDs are
      investigated. The emission properties of QDs are characterized by
      photoluminescence. The composition and bonding structure of oxidized CdSe QDs are
      investigated by X-ray photoelectron spectroscopy (XPS). The XRD peaks of oxidized
      CdSe QDs match CdSe and CdO peaks. CdO is formed by partial oxidation of CdSe
      QDs. Transmission electron microscopy (TEM) image is confirmed morphology of
      oxidation before and after of CdSe QDs.

PMID- 25942916
TI  - Synthesis and properties of an ionic conducting material: in-situ preparation of
      poly(2-ethynyl-N-iodopyridinium iodide) and its electro-optical and
      electrochemical properties.
AB  - Poly(2-ethynyl-N-iodopyridinium iodide) [PEIPI] was easily prepared via in-situ
      uncatalyzed polymerization of 2-ethynylpyridine by using iodine. The activated
      acetylenic bond of 2-ethynyl-N-iodopyridinium iodide formed at the initial
      reaction time was assumed to be susceptible to linear polymerization, followed by
      an identical propagation step that contains the produced macroanion and
      quaternized monomeric species. The polymer structure was characterized by various
      instrumental methods to have the conjugated polymer backbone system bearing the
      designed substituents. The electro-optical and electrochemical properties of
      polymer were studied. The UV-visible spectrum of PEIPI showed a characteristic
      absorption peak in the visible region up to 800 nm. The PL emission spectrum of
      PEIPI shows two peaks at 515 and 550 nm. The cyclic voltammetry of PEIPI
      exhibited irreversible electrochemical behavior between the oxidation and
      reduction peaks.

PMID- 25942917
TI  - A bisindolylmaleimide-naphthalimide building block for the construction of the
      energy transfer cassette.
AB  - Double build-in chromophores with naphthalimide and bisindolylmaleimide
      incorporating to one molecule were synthesized efficiently and characterized
      fully. Its spectral properties were investigated. Effective intramolecular energy
      transfer together with the strong emission in solution and solid state were
      discussed in terms of its electronic structures. Optimized structure and frontier
      molecular orbital were calculated based on D3(mol) platform. Obviously electron
      delocalization before and after excitation was observed according to the
      molecular orbital calculation, which corresponds to the mechanism of excitation
      energy transfer through space occurred in the donor-linker-acceptor molecular
      system. The opto-physical properties of the dye indicated potential application
      of electro-optical materials.

PMID- 25942918
TI  - SnO2 nanowire gas sensor operating at room temperature.
AB  - The NO2 gas sensor based on SnO2 semiconducting nanowires workable at room
      temperature has been investigated. The network structure of SnO2 nanowires was
      fabricated on the electrodes by a simple thermal evaporation process from Sn
      metal powders and oxygen gas. The diameter of the nanowires was 20-60 nm
      depending on the processing conditions. When the concentration of NO2 was 10 ppm,
      the sensitivity of 43, the response time of 38 s, and the recovery time of 25 s
      were observed at the operating temperature of 200 degrees C. In particular, the
      operating temperature of the sensor could be decreased down below 50 degrees C by
      controlling the properties of the nanowires and the structures of the electrodes.
      The sensitivities were 10-15 when the NO2 concentrations were 10-50 ppm at the
      operating temperature of 50 degrees C.

PMID- 25942919
TI  - A comparative study of three cytotoxicity test methods for nanomaterials using
      sodium lauryl sulfate.
AB  - The biocompatibility evaluation of nanomaterials is essential for their medical
      diagnostic and therapeutic usage, where a cytotoxicity test is the simplest form
      of biocompatibility evaluation. Three methods have been commonly used in previous
      studies for the cytotoxicity testing of nanomaterials: trypan blue exclusion,
      colorimetric assay using water soluble tetrazolium (WST), and imaging under a
      microscope following calcein AM/ethidium homodimer-1 staining. However, there has
      yet to be a study to compare each method. Therefore, in this study three methods
      were compared using the standard reference material of sodium lauryl sulfate
      (SLS). Each method of the cytotoxicity test was carried out using mouse
      fibroblasts of L-929 exposed to different concentrations of SLS. Compared to the
      gold standard trypan blue exclusion test, both colorimetric assay using water
      soluble tetrazolium (WST) and imaging under microscope with calcein AM/ethidium
      homodimer-1 staining showed results that were not statistically different. Also,
      each method exhibited various advantages and disadvantages, which included the
      need of equipment, time taken for the experiment, and provision of additional
      information such as cell morphology. Therefore, this study concludes that all
      three methods of cytotoxicity testing may be valid, though careful consideration
      will be needed when selecting tests with regard to time, finances, and the amount
      of information required by the researcher(s).

PMID- 25942920
TI  - Adhesion phenomena between particles according to the content of organic binder
      in core for thin-wall casting.
AB  - The content of organic binder in a core for thin-wall casting has been controlled
      to investigate the adhesion phenomena of inorganic binder between starting
      particles, as directly related to the mechanical and thermal properties of the
      core. The inorganic binder precursor was composed of tetraethyl orthosilicate and
      sodium methoxide as the silicon dioxide and sodium oxide precursors,
      respectively. Poly(vinyl alcohol), a hydrophilic polymer, was used as an organic
      binder. The particles coated with the inorganic precursor were sculpted with the
      organic binder and then the prepared core samples were heated at 1000 degrees C
      for 1 h. The core samples prepared with the optimum content of organic binder
      show the highest fracture strength. This may be due to the enhancement of
      adhesion by the glass phase formed between starting particles. However, when too
      much or too little organic binder is employed, the strength values of the core
      samples are significantly decreased. This is because the network structure of the
      glass phase is not inadequately created or the glass phase is not uniformly
      developed between starting particles, resulting in the insufficient contact
      between starting particles during the convert process.

PMID- 25942921
TI  - Characterization and formic acid oxidation studies of PtAu nanoparticles.
AB  - Characterization and electrocatalytic oxidation of formic acid on PtAu
      nanoparticles supported multiwalled carbon nanotube (MWCNT) were studied.
      Electrochemical measurements were conducted in a self-made conventional three
      electrode glass cell at room temperature. A Pt wire and Ag/AgCl were used as
      auxiliary and reference electrodes, respectively. The Pt was electrodeposited
      onto the electrode and their catalytic activities in the electrooxidation of
      formic acid were examined and compared. The morphology and composition were
      studied by a combination of transmission electron microscopy (TEM) and energy
      dispersive X-ray spectroscopy (EDX). Cyclic voltamograms of formic acid
      electrooxidation show a distinguishing shape with a prominent oxidation peak in
      the forward scan contributed to the formic acid oxidation whilst the backward
      scan is associated with the oxidation of exclusion of carbonaceous species. On
      the basis of the onset potential and current density, the resulting PtAu
      nanoparticles showed much higher electrocatalytic activity than other
      counterparts. The results show an excellent sign of applications for fuel cell.

PMID- 25942922
TI  - The effects of propionic acid on nano-sized BaTiO3 particles synthesized by a
      hydrothermal method.
AB  - The influence of propionic acid on BaTiO3 particles prepared via hydorthermal
      method is discussed. The amount of the acid is varied in the experimental
      processes to enhance understanding of the roles of the propionic acid. Smaller
      sized BaTiO3 powders with more uniform particle sizes can be achieved at 200
      degrees C after 24 h using propionic acid. The acid is found to be excellent for
      size reduction and narrow size distribution. Reitveld refinement of the XRD
      patterns revealed that the synthesize BaTiO3 nanopowders have tetragonal
      asymmetry dominant structures. The "micro-capsules" caused by the acid are
      observed using high temperature in-situ TEM analysis. High vacuum condition of
      the TEM is attributed to the notable differences. It can thus be posited that the
      reduction of particle size and the narrow size distribution result from the
      "micro-capsule" effects of propionic acid. Moreover, the "capsules" are
      attributed to a decrease of intragranular pores in the BaTiO3 particles.

PMID- 25942923
TI  - Shape memory characteristics and mechanical properties of powder metallurgy
      processed Ti50Ni40Cu10 alloy.
AB  - Ti-Ni-Cu alloy powders were prepared by gas atomization and porous bulk specimens
      were fabricated by spark plasma sintering (SPS). The microstructure of as
      solidified powders exhibited a cellular structure and they contained a high
      density of nano-sized porosities which were located in the intercellular regions.
      XRD analysis showed that one-step martensitic transformation of B2-B19 occurred
      in all alloy powders and SPS specimens. When the martensitic transformation start
      temperature (M(s)) and austenite transformation finish temperature (A(f)) were
      determined in order to analyze the dependence of powder size on transformation
      temperatures, the M(s) increased slightly from -17.5 degrees C to - 14.6 degrees
      C as increasing the powder size ranging from between 25 and 50 MUm to ranging
      between 100 and 150 MUm. However, the M(s) and A(f) of the as-atomized powders is
      much smaller than those of SPS specimens and the M(s) of porous specimen was
      about 10.9 degrees C. Loading-unloading compressive tests were carried out to
      investigate the mechanical properties of porous Ti-Ni-Cu specimen. The specimen
      was compressed to the strain of 6% at a temperature higher than A,. After
      unloading, the residual strain was 2.1%. After the compressed specimen was heated
      to 60 degrees C and held for 30 minutes and then cooled to room temperature, the
      changes in the length of the specimens were measured. Then it was found that the
      recovered strain ascribed to shape memory effect was 1.5%.

PMID- 25942924
TI  - Analysis on the design and property of flow field plates of innovative direct
      methanol fuel cell.
AB  - The paper uses technology of lithography process to etch flow fields on single
      side of a printed circuit board (PCB), and combines flow field plate with
      collector plate to make innovative anode flow field plates and cathode flow field
      plates required in direct methanol fuel cell (DMFC), and meanwhile makes membrane
      electrode assembly (MEA) and methanol fuel plate. The flow field plates are
      designed to be in the form of serpentine flow field. The paper measured the
      assembled DMFC to achieve the overall efficiency of DMFC under the conditions of
      different screw torques and different concentration, flow rate and temperature of
      methanol. Experimental results show that when the flow field width of flow field
      plate is 1 mm, the screw torque is 16 kgf/cm, and the concentration, flow rate
      and temperature of methanol-water are 1 M, 180 ml/h and 50 degrees C
      respectively, the prepared DMFC can have better power density of 5.5 mW/cm2, 5.4
      mW/cm2, 11.2 mW/cm2 and 11.8 mW/cm2. Besides, the volume of the DMFC designed and
      assembled by the study is smaller than the generally existing DMFC by 40%.

PMID- 25942925
TI  - A study on the band gap and the doping level of V-doped TiO2 with respect to the
      visible-light photocatalytic activity.
AB  - The visible-light response is a necessary but not a sufficient condition for
      semiconductor photocatalyst to function as a visible-light active photocatalyst.
      To shed more light on the issue of visible-light response of semiconductor
      photocatalysts, the band-gaps and the doping levels of multivalency vanadium
      doped TiO2 were investigated from sonochemically prepared samples. Sonochemical
      doping, which relies on acoustic cavitation phenomena, is a one step process
      excluding chemical synthesis, and three types of vanadium doped TiO2 nanopowder
      were prepared using such vanadium oxides as V2O3, V2O4, and V2O5. The band-gaps
      of as-prepared samples were obtained from the diffuse reflectance measurement,
      and the doping levels of vanadium in these samples were measured using electron
      probe micro analyzer. In addition, X-ray photoelectron spectrometer was
      introduced to complement electron probe micro analyzer. Furthermore, quantum
      chemical calculations on simple cluster models for TiO2 and V-doped TiO2 were
      performed, and the resulting computational results in conjunction with
      experimental findings provided valuable information on oxygen vacancy and doping
      mechanism.

PMID- 25942926
TI  - The effect of inductively-coupled-plasma reactive ion etching power on the
      etching rate and the surface roughness of a sapphire substrate.
AB  - In this study, patterned sapphire substrates are fabricated using nanosphere
      lithography (NSL) and inductively-coupled-plasma reactive ion etching (ICP-RIE).
      Polystyrene nanospheres of approximately 600 nm diameter are self-assembled on c
      plane sapphire substrates by spin-coating. The diameter of the polystyrene
      nanospheres is modified to adjust the etching mask pitch cycle using oxygen
      plasma in the ICP-RIE system. A nickel thin film mask of 100 nm thickness is
      deposited by electron-beam evaporation on a substrate covered with treated
      nanospheres. The sapphire substrate is then etched in an inductively coupled
      plasma system using BCl3/Ar gas, to fabricate a structure with a periodic sub
      micron hole array with different sidewall intervals. The DC bias voltage, the
      sapphire etching rate, the surface roughness, are studied as a function of the
      ICP and the RF power. Different sub-micron hole arrays with spacing cycles of 89
      nm, 139 nm and 167 nm are successfully fabricated on the sapphire substrate,
      using suitable etching parameters.

PMID- 25942927
TI  - Effect of gas nitriding on CO2 corrosion for 35CrMo steel after surface
      nanocrystallization.
AB  - This paper studies the influence of ultrasonic surface rolling procession (USRP)
      and gas nitriding on CO2 corrosion for 35CrMo steel. The microstructure of the
      nanocrystallized surface caused by USRP and the nitrided layer were studied by
      means of HRTEM and optical microscope, respectively. High temperature high
      pressure autoclave was adopted to study the CO2 corrosion behavior of 35CrMo
      steel. The characteristics of CO2 corrosion scales on 35CrMo steel were
      investigated by the SEM, EDS and XRD techniques. The experimental results show
      that after USRP about 250 MUm rheological layer forms on the metal surface, and
      the average grain size is 25 nm. USRP thicken the nitrided layer, 10 hours' gas
      nitriding at 550 degrees C lower the corrosion rate while the combine of gas
      nitriding and USRP enhances the corrosion resistance furthest; and the surface
      nanocrystallization increases the content of Cr and changes the corrosion product
      film from FeCO3 to FeCO3 and Cr2O3, and from loose crystal structure to amorphous
      flocculent structure. The corrosion resistance of 35CrMo has been improved
      significantly by USRP and gas nitriding.

PMID- 25942928
TI  - Process analysis and mechanism investigation of low temperature synthesis of
      nanoscale calcium hexaboride powder.
AB  - The synthesis of nanoscale CaB6 powder via the low temperature chemical reaction
      of Calcium chloride (CaCl2) with Sodium Borohyride (NaBH4) in vacuum has been
      investigated in this study. The reaction temperature was determined by
      differential scanning calorimetry and thermogravimetric analysis (DSC and TG).
      Crystallization process was provided through studying the influence of heat
      preservation time on the crystal particles morphologies in vacuum. X-ray
      diffraction (XRD) was used to investigate the phase and structure of CaB6. The
      characterization for microstructure was performed by transmission electron
      microscopy (TEM) and high resolution transmission electron microscopy (HRTEM).
      The elemental analysis was conducted by X-ray photoelectron spectroscopy (XPS).
      It is concluded that CaB6 nanoparticles can be successfully prepared under low
      temperature at 500 degrees C. The results showed that in vacuum, 2 hours heat
      preservation time is enough for the reaction to complete at this temperature. The
      average size of crystal grains is 25.1 nm with high crystallinity and cubic
      shaped, which particles size is at the range of 20-100 nm. Longer heat
      preservation time more than 2 hours will make CaB6 particles connected together
      to form hard aggregations, that is the sintering process occurred under this
      temperature. However, the crystal grain size changed unobviously accompanying the
      holding time prolong due to the high chemical stability of CaB6. The atomic ratio
      of B to Ca is 5.37:1, less than but close to its stoichiometric ratio 6:1. The
      synthesis process and mechanism were investigated in this paper.

PMID- 25942930
TI  - Synthesis and characterization of silver nanoparticles using a solution plasma
      process.
AB  - In this study, Ag nanoparticles (AgNPs) were synthesized using a solution plasma
      process in which a discharge occurred directly in an aqueous environment with
      various discharge times from 120 to 600 s and discharge voltages from 800 to
      1,000 V. The effects of the discharge time and voltage on the size and shape of
      the AgNPs in the solution plasma process were studied using X-ray diffraction
      (XRD), high resolution transmission electron microscopy (HR-TEM) and a UV-Vis-NIR
      spectrophotometer. The formation of AgNPs was confirmed by the HR-TEM and XRD.
      The transition from spherical nanoparticles to dendritic nanoparticles was
      observed when the discharge time increased, and it was noted that the aggregation
      of AgNPs for dendrites was accelerated as the temperature increased due to the
      plasma in the solution. The average particle size of the AgNPs increased as the
      discharge time and voltage increased.

PMID- 25942929
TI  - Polymer encapsulation of magnesium to control biodegradability and
      biocompatibility.
AB  - Clinical utility of biodegradable magnesium implants is undermined by the
      untimely degradation of these materials in vivo. Their high corrosion rate leads
      to loss of mechanical integrity, peri-implant alkalization and localised
      accumulation of hydrogen gas. Biodegradable coatings were produced on pure
      magnesium using RF plasma polymerisation. A monoterpene alcohol with known anti
      inflammatory and antibacterial properties was used as a polymer precursor. The
      addition of the polymeric layer was found to reduce the degradation rate of
      magnesium in simulated body fluid. The in vitro studies indicated good
      cytocompatibility of non-adherent THP-1 cells and mouse macrophage cells with the
      polymer, and the polymer coated sample. The viability of THP-1 cells was
      significantly improved when in contact with polymer encapsulated magnesium
      compared to unmodified samples. Collectively, these results suggest plasma
      enhanced polymer encapsulation of magnesium as a suitable method to control
      degradation kinetics of this biomaterial.

PMID- 25942931
TI  - Fabrication of multilayer pancakelike basic magnesium carbonate.
AB  - The properties of nanomaterials was strongly affected by their microstructures.
      Here Mg5(CO3)4(OH)2 x 4H2O multilayer pancakelike structures were fabricated
      successfully by reaction of MgCl2 and Na2CO3 in aqueous solution at 363 K. The
      growth process of nanostructures was observed by XRD and SEM. Several transition
      states of multilayer pancakelike basic magnesium carbonates were observed, which
      help to understand better the formation process of this hierarchical
      nanostructures. The formation mechanism of Mg5(CO3)4(OH)2 x 4H2O multilayer
      pancakelike structures was discussed and helical growth was proposed. The
      amorphous nanoparticles were formed firstly. Then nanopartilces aggregated and
      oriented assembly under the direction of chemical bonds with the help of water
      molecules. The multilayer pancakelike basic magnesium carbonates was formed by
      helical growth of wafers along (100) and (001) direction. The diameter and volume
      decreased with the increasing concentration of reactants.

PMID- 25942932
TI  - Fabrication of nanocrystalline surface composite layer on Cu plate under ball
      collisions.
AB  - It was demonstrated that the severe plastic deformation of a surface induced by
      repeated ball collisions can be effectively used for fabrication of the
      nanocrystalline surface composite layers. The Cu disk was fixed at the top of a
      vibration chamber and ball treated. Al, Zr, Ni, Co and Fe were introduced into a
      Cu plate as contaminants from the grinding media one after the other by 15-min
      ball treatment. The composite structure was formed as a result of mechanical
      intermixing of the components. The particle size in as-fabricated layer ranged
      from 2 nm to 20 nm, with average values of about 7 nm. As-fabricated layer
      contained non-equilibrium multicomponent solid solution based on FCC Cu crystal
      structure, Zr-based phase, nanosized steel debris and amorphous phase. The
      hardness of the as-fabricated composite was almost ten times that of the initial
      Cu plate.

PMID- 25942933
TI  - Effect of molybdenum and niobium on the phase formation and hardness of
      nanocrystalline CoCrFeNi high entropy alloys.
AB  - In the present study, influence of molybdenum and niobium additions on phase
      formation during mechanical alloying and spark plasma sintering of CoCrFeNi high
      entropy alloy was studied. Major FCC and minor BCC phase were observed after
      mechanical alloying of CoCrFeNi. However, major FCC and sigma phase were observed
      after spark plasma sintering. A maximum relative density of 95% was obtained with
      the hardness of 570 HV in CoCrFeNi HEA. The phase formation behavior was not
      significantly affected by the addition of molybdenum or niobium. However,
      addition of Mo to CoCrFeNi increased the hardness from 570 HV to 620 HV, and the
      hardness increased to 710 HV with combined addition of molybdenum and niobium.
      After sintering, major FCC phase with crystallite size of 60-70 nm was observed
      in all the compositions. Further, the microstructure and hardness retention was
      observed in CoCrFeNiMo0.2 with annealing temperature up to 800 degrees C.

PMID- 25942934
TI  - Investigation of structural disorder using electron temperature in VHF-PECVD on
      hydrogenated amorphous silicon films for thin film solar cell applications.
AB  - Electrode distances and gas flow ratios are important parameters for fabricating
      intrinsic (i-type) layers of hydrogenated amorphous silicon (a-Si:H) films using
      a very high frequency plasma-enhanced chemical-vapor deposition (VHF-PECVD)
      system. In this work, we investigated the relationship between the electrode
      distances and gas flow ratios on the properties of i-type a-Si:H films. The
      electrical, chemical and structural properties are improved with decreasing
      electrode distances (20-40 mm) at a hydrogen ratio [R (H2/SiH4) = 4], due to the
      low electron temperature and heating effect. A low electron temperature generates
      silane-related-reactive species (SiH3) and decreases structural disorder
      resulting in high quality i-type a-Si:H films. The electrical, chemical and
      structural properties of the a-Si:H films are confirmed using Al coplanar
      electrodes, FTIR, Raman spectroscopy, and spectroscopy ellipsometry (SE). When a
      solar cell is fabricated using the a-Si:H film, J(sc) of 13.2-14.8 mA/cm2,
      photoconductivity of 1.5 x 10(-5)-8.6 x 10(-6) S/cm, Si--H2 content of 0-1.24
      at.%, and hydrogen content of about 10 at.% are obtained. These results together
      with a model of the plasma chemistry indicate that H atoms and SiH3 radicals play
      an important role in the deposition process.

PMID- 25942935
TI  - The grain growth behavior of NiO in thermally-stable mesoporous gadolinium-doped
      ceria network for intermediate-temperature solid oxide fuel cell anode materials.
AB  - The grain growth behavior of NiO nano grains in mesoporous gadolinium-doped ceria
      (GDC) network was investigated for anode materials of intermediate-temperature
      solid oxide fuel cell (SOFC). Both mesoporous GDC and NiO-GDC powders were
      synthesized using tri-block copolymer, Pluronic F127 as a structure-directing
      agent, and then X-ray diffraction, N2 adsorption/desorption isotherms, thermo
      gravimetric analysis, field-emission scanning electron microscopy and
      transmission electron microscopy were used for characterization of the mesoporous
      structure. Mesoporous GDC synthesized using pluronic F127 triblock copolymer had
      ordered double mesoporous structure with an average pore size of 9.68 nm and was
      thermally stable up to 700 degrees C. NiO grains in the mesoporous GDC network
      grew to have an octahedral shape with truncated-edges, but massive NiO
      agglomeration occurred as the calcination temperature increases up to 850 degrees
      C.

PMID- 25942936
TI  - Effect of HCl and H2SO4 treatment of TiO2 powder on the photosensitized
      degradation of aqueous rhodamine B under visible light.
AB  - The acid treatments of TiO2 nanopowder with HCI or H2SO4 solution increase the
      concentration of the hydroxyl group on TiO2 surfaces compared to bare TiO2, which
      acts as a Bronsted acid site. For the case of the HCl-treated TiO2, the
      dissociation of Bronsted acid (proton donor) sites on TiO2 leads to a drop in the
      pH levels of rhodamine B (RhB) dye solutions (leading to the protonation of the
      RhB molecule), which allows the physisorption of the uncharged carboxyl acid
      group on the positively charged TiO2 surface. The carboxyl acid group is believed
      to afford a more efficient charge injection from the Visible-light-excited RhB to
      the conduction band of TiO2 compared to the N-ethyl group, yielding a
      significantly enhanced photodegradation of RhB mainly via the N-de-ethylation
      pathway. For the case of the H2SO4-treated TiO2, although the dissociation of
      Bronsted acid sites on TiO2 is also achieved, its photoactivity is much lower
      than that of the HCl-treated TiO2. It seems that the presence of SO4(2-) on the
      H2SO4-treated TiO2 behaves as an *OH scavenger to prevent the photodegradation of
      the dye.

PMID- 25942937
TI  - [Neuronal organization of the main olfactory bulb revisited].

PMID- 25942938
TI  - [Analysis of influenza A/H3N2 neuraminidase genes obtained from influenza
      patients in the 2011/12 and 2012/13 seasons in Japan].
AB  - BACKGROUND: Influenza virus has neuraminidase (NA), a surface protein with
      enzymatic activity that is essential for virus replication. Mutation may affect
      the effectiveness of NA inhibitors that are used for the treatment of influenza
      patients. In this study, we determined the NA gene sequences from the clinical
      isolates of influenza patients to examine the chronological genetic changes and
      the relation to drug susceptibility. METHODS: For 96 A/H3N2 virus isolates the
      50% inhibitory concentration (IC50) (48 each from the 2011-12 and 12-13 influenza
      seasons) was measured. RT-PCR was done with extracted viral RNA, followed by
      nucleotide sequencing. RESULTS: One putative amino acid mutation, D151N, was
      found in an NA activity-related cite in five of ninety-six tested isolate. The
      mutation did not affect the IC50 value. The mutations identified at amino acid
      positions 387 and 400 were statistically correlated with an increased IC50 value,
      although the change was less than ten times, suggesting no significant difference
      in the clinical effectiveness. A small number .of isolates showed mutation in the
      T and/or B cell epitope region of NA. CONCLUSION: No mutation that affected the
      IC50 value or effectiveness of NAIs was detected. Antigenic mutations of NA,
      which influence the selection of epidemic strains, were not determined.
      Continuous observation will be necessary to further clarify the genetic features
      of NA.

PMID- 25942939
TI  - She's a wonderful nurse and our worthy winner.

PMID- 25942940
TI  - Amanda named Nurse of the Year for tackling domestic violence.

PMID- 25942941
TI  - RCN urges new government to take action on low staff morale.

PMID- 25942942
TI  - Stonewall ranks St Andrew's top of equality index.

PMID- 25942943
TI  - Nepalese Nurse Association appeals for donations to support earthquake fund.

PMID- 25942944
TI  - Nurse sues NHS after trust admits 'terrible error'.

PMID- 25942945
TI  - Staff rally against pay proposal.

PMID- 25942946
TI  - 'Work together towards integration and get heard,' Scottish nurses told.

PMID- 25942948
TI  - Important point of contact for tackling obesity being missed.

PMID- 25942949
TI  - NHS is failing the nation's children.

PMID- 25942950
TI  - Rapid access to nurse-led detox units could save the NHS millions.

PMID- 25942951
TI  - Childhood bullying has greatest impact on mental ill-health.

PMID- 25942952
TI  - Spotlight on the nation's finest nurses.

PMID- 25942953
TI  - Sheer dedication makes Sarah the patients' choice.

PMID- 25942954
TI  - Professionals who have enhanced patients' lives.

PMID- 25942960
TI  - Harmful alcohol use.

PMID- 25942961
TI  - Breaking the cycle of violence.

PMID- 25942963
TI  - Pre-load syringes safely.

PMID- 25942962
TI  - 'You're a nurse in 100 million'.

PMID- 25942971
TI  - Dementia festival of ideas.

PMID- 25942975
TI  - Diabetes Journal.

PMID- 25942976
TI  - Never mind 'efficiencies'--the NHS needs L 30 billion just to stand still.

PMID- 25942977
TI  - England-centric standpoint fails to give readers key information.

PMID- 25942978
TI  - RCN would only decide on a ballot once all the facts were available.

PMID- 25942979
TI  - Guidance helps open discussion of neonate organ donation.

PMID- 25942981
TI  - I feel unsure about how to fulfil the requirements of revalidation.

PMID- 25942982
TI  - Input of clinicians is vital in the shift to digital health care.

PMID- 25942984
TI  - Ethnography: principles, practice and potential.
AB  - Ethnography is a methodology that is gaining popularity in nursing and healthcare
      research. It is concerned with studying people in their cultural context and how
      their behaviour, either as individuals or as part of a group, is influenced by
      this cultural context. Ethnography is a form of social research and has much in
      common with other forms of qualitative enquiry. While classical ethnography was
      characteristically concerned with describing 'other' cultures, contemporary
      ethnography has focused on settings nearer to home. This article outlines some of
      the underlying principles and practice of ethnography, and its potential for
      nursing and healthcare practice. 

PMID- 25942985
TI  - Palliative care for patients with non-malignant respiratory disease.
AB  - Non-malignant respiratory disease is a chronic life-limiting condition that
      requires holistic palliative care. Patients with non-malignant respiratory
      disease have a range of biopsychosocial and spiritual needs, which healthcare
      professionals should recognise and manage effectively. Healthcare professionals
      have an important role in enabling the delivery of effective palliative care to
      this group of patients and their carers, and in recognising the many factors that
      may impede delivery of palliative care. 

PMID- 25942986
TI  - Preceptorship.

PMID- 25942987
TI  - Documentation and record-keeping in pressure ulcer management.
AB  - National and international guidelines recommend the use of clinical assessments
      and interventions to prevent pressure-related skin damage. This includes the
      categorisation of pressure ulcers as avoidable or unavoidable, which is
      challenging in clinical practice, mainly because of poor documentation and record
      keeping for care delivered. Documentation and record-keeping are influenced by
      the individual's employing organisation, maintenance procedures for documentation
      and record-keeping, and local auditing processes. A transfer sticker to enable
      patient assessment and promote pressure ulcer documentation was designed and
      implemented. The transfer sticker captures the date, time and location of a
      pressure ulcer preventive risk assessment and the plan of care to be implemented.
      The increased clarity of record of care achieved by using the transfer sticker
      has enabled the number of avoidable hospital-acquired pressure ulcers resulting
      from poor documentation on admission or ward transfers to be reduced. The
      transfer sticker helps staff identify patients at risk and allows interventions
      to be implemented in a timely manner. 

PMID- 25942989
TI  - Too busy to be sick?

PMID- 25942988
TI  - Engaging patients in pressure ulcer prevention.
AB  - As patients increasingly care for themselves at home, they require accessible
      information to enable informed self-care. This article describes the development
      of an educational electronic application (app) designed for use by patients at
      risk of pressure ulcers, and their carers. The app can be downloaded to Windows,
      Android or Apple smartphones or tablets. The app is based on the current pressure
      ulcer prevention and management guidelines from the National Pressure Ulcer
      Advisory Panel and the National Institute for Health and Care Excellence, and is
      designed to educate patients and carers about how to prevent a pressure ulcer,
      how to recognise a pressure ulcer, and what to do if they suspect they are
      developing a pressure ulcer. We hope the app will be used to help with
      educational conversations among patients, carers and healthcare professionals. 

PMID- 25942991
TI  - Improving the lives of many.

PMID- 25942993
TI  - Preparing for reality.

PMID- 25942994
TI  - Phase 1 study of the safety, pharmacokinetics, and antitumour activity of the
      BCL2 inhibitor navitoclax in combination with rituximab in patients with relapsed
      or refractory CD20+ lymphoid malignancies.
AB  - The oral BCL2 inhibitor navitoclax has moderate single-agent efficacy in chronic
      lymphocytic leukaemia (CLL) and minor activity in lymphoma in Phase 1 trials.
      Navitoclax synergizes with rituximab in preclinical models of B-cell lymphoid
      cancers. We report the safety, pharmacokinetics and clinical activity of this
      combination. Patients received navitoclax (200-325 mg) daily and four standard
      weekly doses of rituximab. Twenty-nine patients were enrolled across three dose
      escalation cohorts and a safety expansion cohort (250 mg/d navitoclax). The
      combination was well tolerated. Common toxicities were mild diarrhoea (79%) and
      nausea (72%). Grade 4 thrombocytopenia occurred in 17% of patients (dose limiting
      at 325 mg/d). CD19(+) counts were severely reduced, while CD3(+) cells (~ 20%)
      and serum immunoglobulin M levels (~ 33%) were also reduced during the first
      year. The maximum tolerated dose for navitoclax in combination was 250 mg/d.
      Pharmacokinetic analyses revealed no apparent interactions between the drugs. The
      response rate in patients with follicular lymphoma was 9/12, including five
      complete responses. All five patients with CLL/small lymphocytic leukaemia
      achieved partial responses. One of nine patients with aggressive lymphoma
      responded. The addition of rituximab to navitoclax 250 mg/d is safe; the
      combination demonstrates higher response rates for low-grade lymphoid cancers
      than observed for either agent alone in previous Phase 1 trials. 

PMID- 25942996
TI  - Slowly progressive behavioural presentation in two UK cases with the R406W MAPT
      mutation.

PMID- 25942995
TI  - Cyclin-dependent kinase-activating kinases CDKD;1 and CDKD;3 are essential for
      preserving mitotic activity in Arabidopsis thaliana.
AB  - For the full activation of cyclin-dependent kinases (CDKs), not only cyclin
      binding but also CDK phosphorylation is required. This activating phosphorylation
      is mediated by CDK-activating kinases (CAKs). Arabidopsis has four genes showing
      similarity to vertebrate-type CAKs, three CDKDs (CDKD;1-CDKD;3) and one CDKF
      (CDKF;1). We previously found that the cdkf;1 mutant is defective in post
      embryonic development, even though the kinase activities of core CDKs remain
      unchanged relative to the wild type. This raised a question about the involvement
      of CDKDs in CDK activation in planta. Here we report that the cdkd;1 cdkd;3
      double mutant showed gametophytic lethality. Most cdkd;1-1 cdkd;3-1 pollen grains
      were defective in pollen mitosis I and II, producing one-cell or two-cell pollen
      grains that lacked fertilization ability. We also found that the double knock-out
      of CDKD;1 and CDKD;3 caused arrest and/or delay in the progression of female
      gametogenesis at multiple steps. Our genetic analyses revealed that the functions
      of CDKF;1 and CDKD;1 or CDKD;3 do not overlap, either during gametophyte and
      embryo development or in post-embryonic development. Consistent with these
      analyses, CDKF;1 expression in the cdkd;1-1 cdkd;3-1 mutant could not rescue the
      gametophytic lethality. These results suggest that, in Arabidopsis, CDKD;1 and
      CDKD;3 function as CAKs controlling mitosis, whereas CDKF;1 plays a distinct
      role, mainly in post-embryonic development. We propose that CDKD;1 and CDKD;3
      phosphorylate and activate all core CDKs, CDKA, CDKB1 and CDKB2, thereby
      governing cell cycle progression throughout plant development. 

PMID- 25942997
TI  - HEDIS Antidepressant Measures Biased by 2013 Revision.

PMID- 25942998
TI  - FDAMA Section 114: Why the Renewed Interest?
AB  - The FDA regulates the use of information by biopharmaceutical companies in their
      promotional activities. Section 114 of the Food and Drug Administration
      Modernization Act of 1997 (FDAMA) was specifically designed to allow companies to
      more readily disseminate health care economic information (HCEI) to those who
      need it for formulary decision making. However, very little HCEI has been
      distributed promotionally under this provision over the past 17 years. There are
      recent discussions by stakeholders regarding the need for updates, revisions, or
      guidance regarding Section 114.In light of recent renewed interest in Section 114
      of the FDAMA, the purpose of this commentary is to equip managed care decision
      makers with the information they need to understand and respond to industry
      communications that are governed by Section 114. This commentary reviews and
      synthesizes the regulatory history and language of the statute and changes to the
      promotion regulation generated by Section 114. It explores the reasons for the
      section's limited use to date, for recent renewed interest, and why changes by
      various stakeholders are suggested at this time. Also discussed is what managed
      care pharmacists need to know about Section 114, and suggestions are included
      regarding the active role pharmacists can play in this change process. Renewed
      interest in FDAMA Section 114 appears to stem largely from the increasingly
      visible and growing interest in comparative effectiveness research, the emergence
      of "big data," the expanding range of data sources available for deriving HCEI,
      and recent court decisions that might indicate a change in the regulatory
      environment. Various stakeholders are proposing recommendations regarding changes
      to FDAMA Section 114. Managed care pharmacists should be aware that companies are
      restricted when communicating HCEI promotional messages; this may mean seeing the
      use of FDAMA Section 114 as the "competent and reliable" effectiveness standard
      in promotion. If the managed care pharmacy community communicates clearly about
      what information it needs and the format in which it wants to receive that
      information, companies, policymakers, and regulatory bodies can work
      collaboratively with managed care pharmacy to create a regulatory environment
      that supports transparent communication of desired information. 

PMID- 25942999
TI  - Cost-effectiveness of comprehensive medication reviews versus noncomprehensive
      medication review interventions and subsequent successful medication changes in a
      Medicare Part D population.
AB  - BACKGROUND: An estimated 1.5 million preventable medication-related adverse
      events occur annually, with some resulting in serious injury and even death. To
      help address this issue, the Centers for Medicare Medicaid Services (CMS) now
      require medication therapy management (MTM) programs to offer comprehensive
      medication reviews (CMRs) to all Medicare Part D beneficiaries at least once a
      year. During a CMR, patients receive an extensive amount of medication and
      educational information. In contrast, noncomprehensive medication reviews (non
      CMRs) are more targeted and focus on resolving a particular medication-related
      problem (MRP) via short patient consultations, patient letters, and direct
      provider interventions.   OBJECTIVE: To conduct a cost-effectiveness analysis
      comparing CMRs with non-CMR interventions on successful medication regimen
      changes and reductions in adverse drug events (ADEs). METHODS: This decision
      analytic model compared the cost-effectiveness of CMRs with other intervention
      methods (non-CMRs) from a payer's perspective. For this model, a successful
      outcome was defined as a beneficiary case devoid of an ADE due to MRPs. The model
      was extensively tested and subjected to a thorough one-way sensitivity analysis
      and a second-order probabilistic sensitivity analysis with 10,000 iterations from
      the variable distributions.  RESULTS: Non-CMR interventions were less costly and
      more effective than CMRs. The point estimate for direct medical costs was $193
      for CMRs and $157 for non-CMRs, and the estimated probability of avoiding an ADE
      was 0.93 and 0.94 for CMRs and non-CMRs, respectively. The 10,000 iteration-Monte
      Carlo simulation scatterplot and cost-effectiveness acceptability curve (CEAC)
      revealed a dominance by non-CMRs in preventing harmful ADEs from cost and
      effectiveness perspectives; however, there was an overlap in the 95% CIs for both
      cost and ADEs prevented. Despite this, a non-CMR intervention saved estimated
      $5,377.08 per ADE prevented. One-way sensitivity analysis indicated the results
      were sensitive to the cost of treating a preventable ADE. In 100% of cases, the
      CEAC demonstrated that non-CMRs were likely the most cost-effective intervention
      regardless of the health plan's willingness to pay.  CONCLUSIONS: The cost
      effectiveness acceptability curve suggests that non-CMR interventions were less
      costly and more effective than CMRs; however, there was overlap in the 95% CIs
      for costs and ADEs prevented. In all cases, the CEAC demonstrated that non-CMRs
      were the most economical intervention with regard to time and cost. Non-CMRs show
      promise as a viable method to address MRPs, reduce ADEs, and improve patient
      related health outcomes.

PMID- 25943000
TI  - Understanding reasons for nonadherence to medications in a medicare part d
      beneficiary sample.
AB  - BACKGROUND: Poor medication adherence is a predictor of poor health outcomes,
      especially in populations with chronic diseases. Although several self-reported
      measures of medication adherence exist, the scope of each is limited.  OBJECTIVE:
      To identify barriers to medication adherence in order to facilitate effective
      delivery of telephone-based medication therapy management (MTM) services to
      beneficiaries of contracted Medicare Part D plans. METHODS: This study used a
      cross-sectional telephone-based questionnaire designed to elicit reasons for low
      medication adherence. Patients were eligible to participate if they were
      identified as nonadherent for an antilipidemic, antihypertensive, or antidiabetic
      agent. Nonadherence was defined as less than 80% of proportion of days covered
      (PDC). The questionnaire included 17 items pertaining to medication use and 3
      demographic items. Data were collected between September 2012 and February 2013.
      Data analyses included descriptive statistics and Rasch analyses. RESULTS: A
      total of 124 patients participated in the telephone survey. Of those completing
      the survey, the majority were patients (97.6%); only 3 surveys (2.4%) were
      completed by caregivers. The sample population had a mean age of 69.8 years (SD =
      9.9), and more than half of participants (60.4%) were female. Nineteen percent of
      respondents received their medications by mail. Medication nonadherence generated
      alerts mostly associated with antilipidemic agents (n = 50, 40.3%), followed by
      antihypertensive drugs (n = 36, 29.0%), and antidiabetic medications (n = 23,
      18.5%). The response categories for medication belief items were collapsed from 4
      to 3 categories to achieve acceptable Rasch model fit (to fit the model and
      approximate interval level data). Ten percent of participants reported having
      medications prescribed either that they did not get or that they obtained but did
      not use. Almost 30% of patients reported having medications prescribed that they
      started using but stopped. However, only 4% of patients reporting adherence
      issues were related to the alert triggering for chronic medications; 96% of
      reports were linked to unrelated medications that did not generate an alert. The
      most common reason cited for medication nonadherence was experiencing side
      effects. CONCLUSIONS: Most participants reported positive beliefs about
      medications and did not report adherence issues related to those triggering
      alerts. MTM programs offer potential solutions to a number of barriers to
      medication adherence and a unique opportunity to raise awareness about the
      importance of medication adherence among members.

PMID- 25943001
TI  - Factors associated with the initiation of biologic disease-modifying
      antirheumatic drugs in Texas Medicaid patients with rheumatoid arthritis.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a progressive autoimmune disorder of
      joints that is associated with high health care costs, yet guidance is lacking on
      how early to initiate biologic disease-modifying antirheumatic drugs (DMARDs), a
      class of medications that is the major cost driver in RA management. Few studies
      have examined the factors associated with the transition from nonbiologic DMARDs,
      the first-line therapy for RA, to biologic DMARDs in RA patients.  OBJECTIVE: To
      examine patient sociodemographics, medication use patterns, and clinical
      characteristics associated with initiation of biologic DMARDs.   METHODS: This
      was a retrospective study using the Texas Medicaid prescription and medical
      claims database from July 1, 2003-December 31, 2010. Adults (aged 18-63 years)
      with an RA diagnosis (ICD-9-CM code 714.xx), no nonbiologic DMARD or biologic
      DMARD use during the 6-month pre-index period, and a minimum of 2 prescription
      claims for the same nonbiologic DMARD during the post-index period were included
      in the study. The index date was defined as the date when the first nonbiologic
      DMARD claim was made. Predictors of initiation of biologic DMARDs were age,
      gender, race, adherence (proportion of days covered), persistence to nonbiologic
      DMARDs, comorbidity (Charlson Comorbidity Index [CCI]), pain medication use,
      glucocorticoid use, and rheumatologist visit. Logistic regression was used to
      examine the factors associated with the initiation of biologic DMARDs.   RESULTS:
      A total of 2,714 patients were included. After controlling for patient
      characteristics, logistic regression showed, that compared with methotrexate
      (MTX) users, sulfasalazine (SSZ) and hydroxychloroquine (HCQ) users were less
      likely to initiate biologic DMARDs by 69.0% (OR = 0.310, 95% CI = 0.221-0.434, P 
      less than  0.0001) and 79.9% (OR = 0.201, 95% CI = 0.152-0.265, P  less than 
      0.0001), respectively. Nonbiologic DMARD dual therapy users were 39.1% less
      likely to initiate biologic DMARDs compared with nonbiologic DMARD monotherapy
      users (OR = 0.609, 95% CI = 0.463-0.803, P = 0.0004). With each year increase in
      age, patients were 1.6% less likely to start biologic DMARDs (OR = 0.984, 95% CI
      = 0.975-0.993, P = 0.0006). Compared with glucocorticoid users, glucocorticoid
      nonusers were 53.8% less likely to start on biologic DMARDs (OR = 0.462, 95% CI =
      0.372-0.573, P  less than  0.0001). Patients with CCI scores of >= 3 were
      approximately 1.6 times more likely to initiate biologic DMARDs than those with
      CCI scores of 1 (OR = 1.618, 95% CI = 1.228-2.132, P = 0.0006).  CONCLUSIONS:
      Younger age, CCI scores >=3, glucocorticoid use, MTX users (vs. SSZ and HCQ
      users), and nonbiologic DMARD monotherapy users (vs. dual therapy users) were
      significantly associated with higher likelihood to initiate biologic DMARDs.
      Recognizing these potential factors that drive the initiation of biologic DMARDs
      in this patient population, health care providers and Texas Medicaid should take
      measures to achieve optimal therapy for RA patients through thorough RA
      medication evaluation, well-structured RA monitoring programs, and patient
      education.

PMID- 25943002
TI  - Comparative Efficacy of Novel DMARDs as Monotherapy and in Combination with
      Methotrexate in Rheumatoid Arthritis Patients with Inadequate Response to
      Conventional DMARDs: A Network Meta-Analysis.
AB  - BACKGROUND: Given the availability of a number of alternative biologic treatment
      options and other novel disease-modifying antirheumatic drugs (DMARDs) for the
      treatment of patients with rheumatoid arthritis (RA), clinicians are faced with
      an increasingly challenging choice regarding optimal treatment. Biologics are
      usually combined with traditional DMARDs, primarily methotrexate (MTX), but some
      biologics and tofacitinib (together referred to in this article as novel DMARDs)
      have been shown to be efficacious as monotherapy as well. In real-world practice,
      approximately one-third of RA patients receiving biologics are on monotherapy,
      primarily because of intolerance of, or noncompliance with, MTX. Limited data,
      however, are available analyzing the effectiveness of monotherapy compared with
      combination therapy across novel DMARDs. OBJECTIVE: To compare American College
      of Rheumatology (ACR) responses to approved novel DMARDs used as monotherapy or
      as combination therapy with methotrexate (MTX) at 24 weeks in RA patients who
      have shown inadequate response to conventional DMARDs (DMARD-IR).  METHODS:
      Through a systematic review of the literature, we identified randomized
      controlled trials that assessed approved novel DMARDs used as monotherapy or as
      combination therapy with MTX in DMARD-IR RA patients. Twenty-eight RCTs were
      identified that evaluated abatacept, anakinra, adalimumab, certolizumab pegol,
      etanercept, golimumab, infliximab, tocilizumab, or tofacitinib. ACR responses at
      24 weeks were extracted and combined by means of Bayesian network meta-analyses. 
      RESULTS: With the exception of anakinra plus MTX, which was less efficacious,
      most novel DMARDs, when used in combination with MTX, demonstrated comparable ACR
      responses. When novel DMARDs were used as monotherapies, greater ACR20/50/70
      responses were observed with tocilizumab than with anti-tumor necrosis factor
      agents (aTNF) or tofacitinib. Furthermore, ACR20/50/70 responses with tocilizumab
      plus MTX were similar to those with tocilizumab monotherapy (odds ratio [OR] for
      the indirect comparison = 1.08, 95% credible interval [CrI] = 0.40-2.84; OR =
      1.24, CrI = 0.44-3.61; OR = 0.95, CrI = 0.33-2.72, respectively), whereas greater
      responses were observed with aTNF plus MTX than with aTNF monotherapy (OR = 2.41,
      CrI = 0.51-11.61; OR = 2.85, CrI = 0.51-17.67; OR = 1.28, CrI = 0.21-8.42,
      respectively). Relative efficacy estimates for the indirect comparison of
      tofacitinib plus MTX with tofacitinib monotherapy were very uncertain.
      CONCLUSIONS: Results suggest that in combination with MTX most of the available
      novel DMARDs have similar levels of efficacy in DMARD-IR patients. As
      monotherapy, however, tocilizumab displayed higher ACR responses than aTNF or
      tofacitinib. ACR responses with tocilizumab plus MTX were similar to those with
      tocilizumab as monotherapy, whereas aTNF in combination with MTX demonstrated
      greater ACR responses than aTNF as monotherapy.

PMID- 25943004
TI  - Nitrogen-Doped Reduced Graphene Oxide as a Bifunctional Material for Removing
      Bisphenols: Synergistic Effect between Adsorption and Catalysis.
AB  - Nitrogen modified reduced graphene oxide (N-RGO) was prepared by a hydrothermal
      method. The nitrogen modification enhanced its adsorption and catalysis ability.
      For an initial bisphenol concentration of 0.385 mmol L(-1), the adsorption
      capacity of N-RGO was evaluated as 1.56 and 1.43 mmol g(-1) for bisphenol A (BPA)
      and 1.43 mmol g(-1) for bisphenol F (BPF), respectively, both of which were about
      1.75 times that (0.90 and 0.84 mmol g(-1)) on N-free RGO. N-RGO could activate
      persulfate, producing strong oxidizing sulfate radicals. The apparent degradation
      rate constant of BPA on N-RGO was 0.71 min(-1), being about 700 times that (0.001
      min(-1)) on N-free RGO. In mixtures of various phenols, the degradation rate
      constant of each phenol was linearly increased with its adsorption capacity. A
      simultaneous use of N-RGO and persulfate yielded fast and efficient removal of
      bisphenols. The use of N-RGO (120 mg L(-1)) and persulfate (0.6 mmol L(-1))
      almost completely removed the added bisphenols (0.385 mmol L(-1)) at pH 6.6
      within 17 min. A mechanism study indicated that the adsorption enriched the
      pollutant, and the catalytically generated sulfate radicals rapidly degrade the
      adsorbed pollutant, accelerating in turn the adsorption of residual pollutant. 

PMID- 25943003
TI  - Predictors of start of different antidepressants in patient charts among patients
      with depression.
AB  - BACKGROUND: In usual psychiatric care, antidepressant treatments are selected
      based on physician and patient preferences rather than being randomly allocated,
      resulting in spurious associations between these treatments and outcome studies.
      OBJECTIVE: To identify factors recorded in electronic medical chart progress
      notes predictive of antidepressant selection among patients who had received a
      depression diagnosis.  METHODS: This retrospective study sample consisted of 556
      randomly selected Veterans Health Administration patients diagnosed with
      depression from April 1, 1999, to September 30, 2004, stratified by the
      antidepressant agent, geographic region, gender, and year of depression cohort
      entry. Predictors were obtained from administrative data, and additional
      variables were abstracted from electronic medical chart notes in the year prior
      to the start of the antidepressant in 5 categories: clinical symptoms and
      diagnoses, substance use, life stressors, behavioral/ideation measures (e.g.,
      suicide attempts), and treatments received. Multinomial logistic regression
      analysis was used to assess the predictors associated with different
      antidepressant prescribing, and adjusted relative risk ratios (RRR) were
      reported. RESULTS: Of the administrative data-based variables, gender, age,
      illicit drug abuse or dependence, and number of psychiatric medications in the
      prior year were significantly associated with antidepressant selection. After
      adjusting for administrative data-based variables, sleep problems (relative risk
      ratio [RRR] = 2.47) or marital issues (RRR = 2.64) identified in the charts were
      significantly associated with prescribing mirtazapine rather than sertraline;
      however, no other chart-based variables showed a significant association or an
      association with a large magnitude.  CONCLUSIONS: Some chart data-based variables
      were predictive of antidepressant selection, but we neither found many nor found
      them highly predictive of antidepressant selection in patients treated for
      depression.

PMID- 25943005
TI  - Renal function and symptoms/adverse effects in opioid-treated patients with
      cancer.
AB  - BACKGROUND: Renal impairment and the risk of toxicity caused by accumulation of
      opioids and/or active metabolites is an under-investigated issue. This study
      aimed at analysing if symptoms/adverse effects in opioid-treated patients with
      cancer were associated with renal function. METHODS: Cross-sectional multicentre
      study (European Pharmacogenetic Opioid Study, 2005-2008), in which 1147 adult
      patients treated exclusively with only one of the most frequently reported
      opioids (morphine/oxycodone/fentanyl) for at least 3 days were analysed. Fatigue,
      nausea/vomiting, pain, loss of appetite, constipation and cognitive dysfunction
      were assessed (EORTC QLQ-C30). Glomerular filtration rate (GFR) was estimated
      using Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and
      Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI Creatinine) equations.
      RESULTS: Mild to severe low GFR was observed among 40-54% of patients. CG
      equation showed that patients with mild and moderate/severe low GFR on morphine
      treatment had higher odds of having severe constipation (P < 0.01) than patients
      with normal GFR. In addition, patients with moderate/severe low GFR on morphine
      treatment were more likely to have loss of appetite (P = 0.04). No other
      significant associations were found. CONCLUSION: Only severe constipation and
      loss of appetite were associated with low GFR in patients treated with morphine.
      Oxycodone and fentanyl, in relation to the symptoms studied, seem to be safe as
      used and titrated in routine cancer pain care.

PMID- 25943006
TI  - The effectiveness of environmental strategies on noise reduction in a pediatric
      intensive care unit: creation of single-patient bedrooms and reducing noise
      sources.
AB  - PURPOSE: Noise is a substantial problem for both patients and healthcare workers
      in hospitals. This study aimed to determine the effectiveness of environmental
      strategies (creating single-patient rooms and reducing noise sources) in noise
      reduction in a pediatric intensive care unit. DESIGN AND METHODS: Noise
      measurement in the unit was conducted in two phases. In the first phase,
      measurements aimed at determining the unit's present level of noise were
      performed over 4 weeks in December 2013. During the month following the first
      measurement phase, the intensive care unit (ICU) was moved to a new location and
      noise-reducing strategies were implemented. The second phase, in May 2014,
      measured noise levels in the newly constructed environment. RESULTS: The noise
      levels before and after environmental changes were statistically significant at
      72.6 dB-A and 56 dB-A, respectively (p < .05). PRACTICE IMPLICATIONS: Single
      patient rooms and noise-reducing strategies can be effective in controlling
      environmental noise in the ICU.

PMID- 25943008
TI  - [Study of Health Education in Secondary Schools in Albacete in 2014].

PMID- 25943007
TI  - Accumulation of type VI collagen in the primary osteon of the rat femur during
      postnatal development.
AB  - In rodents, the long bone diaphysis is expanded by forming primary osteons at the
      periosteal surface of the cortical bone. This ossification process is thought to
      be regulated by the microenvironment in the periosteum. Type VI collagen (Col
      VI), a component of the extracellular matrix (ECM) in the periosteum, is involved
      in osteoblast differentiation at early stages. In several cell types, Col VI
      interacts with NG2 on the cytoplasmic membrane to promote cell proliferation,
      spreading and motility. However, the detailed functions of Col VI and NG2 in the
      ossification process in the periosteum are still under investigation. In this
      study, to clarify the relationship between localization of Col VI and formation
      of the primary osteon, we examined the distribution of Col VI and osteoblast
      lineages expressing NG2 in the periosteum of rat femoral diaphysis during
      postnatal growing periods by immunohistochemistry. Primary osteons enclosing the
      osteonal cavity were clearly identified in the cortical bone from 2 weeks old.
      The size of the osteonal cavities decreased from the outer to the inner region of
      the cortical bone. In addition, the osteonal cavities of newly formed primary
      osteons at the outermost region started to decrease in size after rats reached
      the age of 4 weeks. Immunohistochemistry revealed concentrated localization of
      Col VI in the ECM in the osteonal cavity. Col VI-immunoreactive areas were
      reduced and they disappeared as the osteonal cavities became smaller from the
      outer to the inner region. In the osteonal cavities of the outer cortical
      regions, Runx2-immunoreactive spindle-shaped cells and mature osteoblasts were
      detected in Col VI-immunoreactive areas. The numbers of Runx2-immunoreactive
      cells were significantly higher in the osteonal cavities than in the osteogenic
      layers from 2 to 4 weeks. Most of these Runx2-immunoreactive cells showed NG2
      immunoreactivity. Furthermore, PCNA-immunoreactivity was detected in the Runx2
      immunoreactive spindle cells in the osteonal cavities. These results indicate
      that Col VI provides a characteristic microenvironment in the osteonal cavity of
      the primary osteon, and that differentiation and proliferation of the osteoblast
      lineage occur in the Col VI-immunoreactive area. Interaction of Col VI and NG2
      may be involved in the structural organization of the primary osteon by
      regulating osteoblast lineages. 

PMID- 25943010
TI  - Successive Reduction Dry Milling of Normal and Waxy Corn: Grain, Grit, and Flour
      Properties.
AB  - Dry milling of different corn types resulted in varied proportions of germ,
      pericarp, grit and flour. Grit and flour produced during different reduction
      stages varied in particle size and chemical constituents, hence applications in
      food industry. In this study, recovery of different fractions and variation in
      physicochemical and pasting properties of grit and flour fractions obtained
      during 3 successive reduction dry millings of 2 normal (African tall, HQPM1) and
      1 waxy corn (IC 550353) were evaluated. Waxy corn grains had the highest L*, a*,
      b*, ash, fat, and protein content and the lowest weight. Waxy and African tall
      gave the highest recovery of germ and pericarp, respectively. Waxy corn showed
      lower grit and flour recovery as compared to normal corn. Flour fractions showed
      higher L* and lower a* and b* values than grit fractions. Particle size of grit
      and flour fractions ranged from 840 to 982 MUm and 330 to 409 MUm, respectively.
      Fractions with larger particle size showed lower L* value. The b* value showed
      positive correlation with yellow pigment content. Grit and flour from the 1st
      reduction stage showed higher ash and fat content. Protein content was correlated
      positively with ash content and negatively with L* value. Grit and flour
      fractions with higher protein content had lower pasting viscosities. Pasting
      viscosities were higher for flours than their corresponding grits. Protein
      profiling of grit and flour fractions from different stages showed quantitative
      and qualitative differences in medium (22, 28, and 35 kDa) and low molecular
      weight (16, 17, and 19 kDa) polypeptides and were related to grit and flour
      yield. 

PMID- 25943009
TI  - When a patient's ethnicity is declared, medical students' decision-making
      processes are affected.
AB  - BACKGROUND: Disparity in health status and healthcare outcomes is widespread and
      well known. This holds true for Indigenous peoples in many settings including
      Australia and Hawaii. While multi-factorial, there is increasing evidence of
      health practitioner contribution to this disparity. This research explored senior
      medical students' clinical decision-making processes. METHODS: A qualitative
      study was conducted in 2014 with 30 final year medical students from The
      University of Melbourne, Australia, and The John Burns Medical School, Hawaii,
      USA. Each student responded to questions about a paper-based case, first in
      writing and elaborated further in an interview. Half the students were given a
      case of a patient whose ethnicity was not declared; the other half considered the
      patient who was Native Hawaiian or Australian Aboriginal. A systematic thematic
      analysis of the interview transcripts was conducted. RESULTS: The study detected
      subtle biases in students' ways of talking about the Indigenous person and their
      anticipation of interacting with her as a patient. Four main themes emerged from
      the interview transcripts: the patient as a person; constructions of the person
      as patient; patient-student/doctor interactions; and the value of various
      education settings. There was a strong commitment to the patient's agenda and to
      the element of trust in the doctor-patient interaction. CONCLUSION: These
      findings will help to advance medical curricula so that institutions graduate
      physicians who are increasingly able to contribute to equitable outcomes for all
      patients in their care. The study also draws attention to subtle biases based on
      ethnicity that may be currently at play in physicians' practices.

PMID- 25943011
TI  - A single-centre observational cohort study of admission National Early Warning
      Score (NEWS).
AB  - INTRODUCTION: Early warning scores are commonly used in hospitals to identify
      patients at risk of deterioration. The National Early Warning Score (NEWS) has
      recently been introduced to UK practice. However, it is not yet widely
      implemented. We aimed to compare NEWS to the early warning score currently used
      in our hospital--the Patient at Risk Score (PARS). METHODS: We conducted a
      prospective observational cohort study of all adult general medical patients
      admitted to a single hospital over a 20-day period. Physiological data and early
      warning scores recorded in bedside charts were collected on admission and a NEWS
      score was retrospectively calculated. The patient notes were reviewed at 48 h
      after admission. The primary outcome was a composite of critical care admission
      or death within 2 days of admission. The secondary outcome was hospital length of
      stay. RESULTS: NEWS was more strongly associated with the primary outcome than
      PARS (odds ratio 1.54, p < 0.001 compared to 1.42, p = 0.056). A NEWS of 3 or
      more was associated with the primary outcome (odds ratio 7.03, p = 0.003).
      Neither score was correlated with hospital length of stay. CONCLUSION: NEWS on
      admission is superior to PARS for identifying patients at risk of death or
      critical care admission within the first 2 days of hospital stay. Current
      guidelines advocate a threshold of 5 for triggering a clinical review. However,
      since a score of 3 or more was associated with a poor outcome, this
      recommendation should be reviewed. Both scores were poor predictors of hospital
      length of stay.

PMID- 25943012
TI  - Two glycerol uptake systems contribute to the high osmotolerance of
      Zygosaccharomyces rouxii.
AB  - The accumulation of glycerol is essential for yeast viability upon hyperosmotic
      stress. Here we show that the osmotolerant yeast Zygosaccharomyces rouxii has two
      genes, ZrSTL1 and ZrSTL2, encoding transporters mediating the active uptake of
      glycerol in symport with protons, contributing to cell osmotolerance and
      intracellular pH homeostasis. The growth of mutants lacking one or both
      transporters is affected depending on the growth medium, carbon source, strain
      auxotrophies, osmotic conditions and the presence of external glycerol. These
      transporters are localised in the plasma membrane, they transport glycerol with
      similar kinetic parameters and besides their expected involvement in the cell
      survival of hyperosmotic stress, they surprisingly both contribute to an
      efficient survival of hypoosmotic shock and to the maintenance of intracellular
      pH homeostasis under non-stressed conditions. Unlike STL1 in Sa. cerevisiae, the
      two Z. rouxii STL genes are not repressed by glucose, but their expression and
      activity are downregulated by fructose and upregulated by non-fermentable carbon
      sources, with ZrSTL1 being more influenced than ZrSTL2. In summary, both
      transporters are highly important, though Z. rouxii CBS 732(T) cells do not use
      external glycerol as a source of carbon. 

PMID- 25943022
TI  - On "The role of parents in the ontogeny of achievement-related motivation and
      behavioral choices".
AB  - This monograph offers a comprehensive test of an important theory of motivation.
      Because the theory is sufficiently precise to permit disconfirmation, the results
      that support and those that fail to support it are both informative. The finding
      that parents' influence appears primarily for peripheral subjects (sports and
      music), but not for reading and math raises many issues for further research. The
      study also informs our understanding of gender differences in motivation. 

PMID- 25943024
TI  - The role of parents in the ontogeny of achievement-related motivation and
      behavioral choices.
AB  - Parents believe what they do matters. But, how does it matter? How do parents'
      beliefs about their children early on translate into the choices those children
      make as adolescents? The Eccles' expectancy-value model asserts that parents'
      beliefs about their children during childhood predict adolescents' achievement
      related choices through a sequence of processes that operate in a cumulative,
      cascading fashion over time. Specifically, parents' beliefs predict parents'
      behaviors that predict their children's motivational beliefs. Those beliefs
      predict children's subsequent choices. Using data from the Childhood and Beyond
      Study (92% European American; N = 723), we tested these predictions in the
      activity domains of sports, instrumental music, mathematics, and reading across a
      12-year period. In testing these predictions, we looked closely at the idea of
      reciprocal influences and at the role of child gender as a moderator. The cross
      lagged models generally supported the bidirectional influences described in
      Eccles' expectancy-value model. Furthermore, the findings demonstrated that: (a)
      these relations were stronger in the leisure domains than in the academic
      domains, (b) these relations did not consistently vary based on youth gender, (c)
      parents were stronger predictors of their children's beliefs than vice versa, and
      (d) adolescents' beliefs were stronger predictors of their behaviors than the
      reverse. The findings presented in this monograph extend our understanding of the
      complexity of families, developmental processes that unfold over time, and the
      extent to which these processes are universal across domains and child gender.

PMID- 25943025
TI  - Coupling actin dynamics to phase-field in modeling neural growth.
AB  - In this paper we model the growth of a neural cell together with the actin
      dynamics taking place at its growing region by constructing a phase-field model.
      This is done by assigning auxiliary fields to different constituents of the cell
      in order to differentiate them. Specifically, the inner and outer regions of the
      neural cell are described by phi = 1 and phi = 0 respectively, whereas the inside
      and outside of its leading edge are portrayed by psi = 1 and psi = 0. This
      formulation inherently locates the boundary, which is required to determine the
      evolution of the underlying actin dynamics. Therefore, it provides an alternative
      to boundary tracking algorithms. Then the equations governing the molecular
      workings of the cell specifically those of actin are modified in order to satisfy
      their corresponding boundary conditions. 

PMID- 25943026
TI  - Reno-protection of G004, a novel anti-diabetic sulfonylurea in db/db mice.
AB  - 1-[4-[2-(4-Bromobenzene-sulfonamino)ethyl]phenylsulfonyl]-3-(trans-4
      methylcyclohexyl) urea (G004, CAS865483-06-3) is a synthetic sulfonylurea,
      incorporating the hypoglycemic active structure of glimepiride (CAS 93479-97-1)
      and anti-TXA2 receptor (TP) active structure of BM-531(CAS 284464-46-6). In this
      study, we evaluated the effect of G004 on hyperglycemia and dyslipidemia as well
      as diabetic nephropathy (DN) in db/db mice by gavage over 90 consecutive days of
      treatment. The fasting blood glucose (FBG), glucose, and insulin tolerance as
      well as dyslipidemia were effectively ameliorated in db/db mice treated with
      G004. Interestingly, renal histological results of db/db mice revealed that G004
      markedly reversed the expansion of mesangial extracellular matrix (ECM), the
      early hallmark of DN. Indeed, G004 treatment downregulated the renal expressions
      of type 4 collagen (Col IV) and transforming growth factor-beta1 (TGF-beta1) in
      db/db mice. In addition, imbalance in expressions of matrix metalloproteinase-9
      (MMP-9) and its tissue inhibitor-1 (TIMP-1) in db/db mice kidneys was observed.
      However, G004 increased and decreased the expressions of MMP-9 and TIMP-1,
      respectively. It is well known that TGF-beta pathway signaling plays an essential
      role in hyperglycemia-induced cell protein synthesis. On the other hand, MMP/TIMP
      system is responsible for the breakdown and turnover of ECM. Thus, we speculate
      that G004 possibly attenuated ECM accumulation via remodeling the synthesis and
      degradation of ECM component Col IV through modulation in TGF-beta1 and MMP
      9/TIMP-1 expressions in kidneys of db/db mice. Results from this study provide a
      strong rationale for G004 to be an efficient glucose-controlling agent with
      significant reno-protective properties. 

PMID- 25943028
TI  - Erratum to: Abstract supplement Deutsche Gesellschaft fur Experimentelle und
      Klinische Pharmakologie und Toxikologie e.V. Abstracts of the 81(th) Annual
      Meeting, March 10-12, 2015, Kiel, Germany.

PMID- 25943027
TI  - Salvianolic acid A attenuates TNF-alpha- and D-GalN-induced ER stress-mediated
      and mitochondrial-dependent apoptosis by modulating Bax/Bcl-2 ratio and calcium
      release in hepatocyte LO2 cells.
AB  - Salvianolic acid (Sal A) is a water-soluble compound extracted from Radix Salvia
      miltiorrhiza (danshen), which has been widely used to treat acute hepatitis and
      hepatic damage in traditional Chinese medicine. The aim of the present study was
      to delineate the antiapoptotic signaling pathways involved in Sal A's hepato
      protective action in hepatocyte LO2 cells and to further elucidate the mechanism
      by which Sal A elicits the antiapoptotic effects on hepatocytes. Here, the study
      showed that Sal A had antiapoptotic effects on the TNF-alpha/D-GalN-treated LO2
      cells. Moreover, Western blotting demonstrated that the levels of p-eIF2alpha,
      ATF4, GRP78, CHOP and caspase-4 were markedly decreased in Sal A group.
      Additionally, the decrease of the cell mitochondrial membrane permeability and
      increase of DeltaPsim were detected in Sal A-treated cells by high-content
      screening (HCS) analysis. And the levels of cleaved-caspase-9, cleaved-caspase-3,
      apoptosis-inducing factor (AIF), Apaf-1, and Cytc (cyto) were downregulated,
      while Cytc (mito) was upregulated by Sal A via Western blotting. Furthermore, the
      decreased levels of Bax/Bcl-2 ratio and calcium release were measured in Sal A
      treated cells. In summary, Sal A attenuates TNF-alpha- and D-GalN-induced both ER
      stress and mitochondrial-dependent apoptosis by suppression of Bax/Bcl-2 ratio
      and prevention of calcium release, which support the notion that Sal A could be
      developed into a novel hepatic protectant. 

PMID- 25943029
TI  - Resveratrol improves hepatic steatosis by inducing autophagy through the cAMP
      signaling pathway.
AB  - SCOPE: Resveratrol (RSV), a natural polyphenol, has been reported to attenuate
      nonalcoholic fatty liver disease (NAFLD); however, its underlying mechanism is
      unclear. Autophagy was recently identified as a critical protective mechanism
      during NAFLD development. Therefore, we investigated the role of autophagy in the
      beneficial effects of RSV on hepatic steatosis. METHODS AND RESULTS: Via Oil red
      O staining, triglyceride, and beta-hydroxybutyrate detection, we found that RSV
      decreased palmitate-induced lipid accumulation and stimulated fatty acid beta
      oxidation in hepatocytes. Based on Western blot assay, confocal microscopy and
      transmission electron microscopy, we found that RSV induced autophagy in
      hepatocytes, whereas autophagy inhibition markedly abolished RSV-mediated hepatic
      steatosis improvement. Moreover, RSV increased cAMP levels and the levels of
      SIRT1 (sirtuin 1), pPRKA (phosphorylated protein kinase A), and pAMPK
      (phosphorylated AMP-activated protein kinase), as well as SIRT1 activity in HepG2
      cells. Incubation with inhibitors of AC (adenylyl cyclase), PRKA, AMPK, SIRT1, or
      with AC, PRKA, AMPK, or SIRT1 siRNA abolished RSV-mediated autophagy. Similar
      results were obtained in mice with hepatic steatosis. CONCLUSION: RSV improved
      hepatic steatosis partially by inducing autophagy via the cAMP-PRKA-AMPK-SIRT1
      signaling pathway, which provides new evidence regarding RSV's effects on NAFLD
      treatment.

PMID- 25943030
TI  - Minimally invasive (13)C-breath test to examine phenylalanine metabolism in
      children with phenylketonuria.
AB  - BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive disorder caused by
      deficiency of hepatic phenylalanine hydroxylase (PAH) leading to increased levels
      of phenylalanine in the plasma. Phenylalanine levels and phenylalanine
      hydroxylase (PAH) activity monitoring are currently limited to conventional blood
      dot testing. 1-(13)C-phenylalanine, a stable isotope can be used to examine
      phenylalanine metabolism, as the conversion of phenylalanine to tyrosine occurs
      in vivo via PAH and subsequently releases the carboxyl labeled (13)C as (13)CO2
      in breath. OBJECTIVE: Our objective was to examine phenylalanine metabolism in
      children with PKU using a minimally-invasive 1-(13)C-phenylalanine breath test
      ((13)C-PBT). DESIGN: Nine children (7 M: 2 F, mean age 12.5 +/- 2.87 y) with PKU
      participated in the study twice: once before and once after sapropterin
      supplementation. Children were provided 6 mg/kg oral dose of 1-(13)C
      phenylalanine and breath samples were collected at 20 min intervals for a period
      of 2h. Rate of CO2 production was measured at 60 min post-oral dose using
      indirect calorimetry. The percentage of 1-(13)C-phenylalanine exhaled as (13)CO2
      was measured over a 2h period. Prior to studying children with PKU, we tested the
      study protocol in healthy children (n = 6; 4M: 2F, mean age 10.2 +/- 2.48 y) as
      proof of principle. RESULTS: Production of a peak enrichment (Cmax) of (13)CO2 (%
      of dose) in all healthy children occurred at 20 min ranging from 17-29% of dose,
      with a subsequent return to ~5% by the end of 2h. Production of (13)CO2 from 1
      (13)C-phenylalanine in all children with PKU prior to sapropterin treatment
      remained low. Following sapropterin supplementation for a week, production of
      (13)CO2 significantly increased in five children with a subsequent decline in
      blood phenylalanine levels, suggesting improved PAH activity. Sapropterin
      treatment was not effective in three children whose (13)CO2 production remained
      unchanged, and did not show a reduction in blood phenylalanine levels and
      improvement in dietary phenylalanine tolerance. CONCLUSIONS: Our study shows that
      the (13)C-PBT can be a minimally invasive, safe and reliable measure to examine
      phenylalanine metabolism in children with phenylketonuria. The breath data are
      corroborated by blood phenylalanine levels in children who had increased
      responses in (13)CO2 production, as reviewed post-hoc from clinical charts.

PMID- 25943031
TI  - Expanding the clinical and molecular characteristics of PIGT-CDG, a disorder of
      glycosylphosphatidylinositol anchors.
AB  - PIGT-CDG, an autosomal recessive syndromic intellectual disability disorder of
      glycosylphosphatidylinositol (GPI) anchors, was recently described in two
      independent kindreds [Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 3
      (OMIM, #615398)]. PIGT encodes phosphatidylinositol-glycan biosynthesis class T,
      a subunit of the heteropentameric transamidase complex that facilitates the
      transfer of GPI to proteins. GPI facilitates attachment (anchoring) of proteins
      to cell membranes. We describe, at ages 7 and 6 years, two children of non
      consanguineous parents; they had hypotonia, severe global developmental delay,
      and intractable seizures along with endocrine, ophthalmologic, skeletal, hearing,
      and cardiac anomalies. Exome sequencing revealed that both siblings had compound
      heterozygous variants in PIGT (NM_015937.5), i.e., c.918dupC, a novel duplication
      leading to a frameshift, and c.1342C > T encoding a previously described missense
      variant. Flow cytometry studies showed decreased surface expression of GPI
      anchored proteins on granulocytes, consistent with findings in previous cases.
      These siblings further delineate the clinical spectrum of PIGT-CDG, reemphasize
      the neuro-ophthalmologic presentation, clarify the endocrine features, and add
      hypermobility, low CSF albumin quotient, and hearing loss to the phenotypic
      spectrum. Our results emphasize that GPI anchor-related congenital disorders of
      glycosylation (CDGs) should be considered in subjects with early onset severe
      seizure disorders and dysmorphic facial features, even in the presence of a
      normal carbohydrate-deficient transferrin pattern and N-glycan profiling.
      Currently available screening for CDGs will not reliably detect this family of
      disorders, and our case reaffirms that the use of flow cytometry and genetic
      testing is essential for diagnosis in this group of disorders.

PMID- 25943033
TI  - CD47 protein expression in acute myeloid leukemia: A tissue microarray-based
      analysis.
AB  - Binding of CD47 to signal regulatory protein alpha (SIRPalpha), an inhibitory
      receptor, negatively regulates phagocytosis. In acute myeloid leukemia (AML),
      CD47 is overexpressed on peripheral blasts and leukemia stem cells and inversely
      correlates with survival. Aim of the study was to investigate the correlation
      between CD47 protein expression by immunohistochemistry (IHC) in a bone marrow
      (BM) tissue microarray (TMA) and clinical outcome in AML patients. CD47 staining
      on BM leukemia blasts was scored semi-quantitatively and correlated with clinical
      parameters and known prognostic factors in AML. Low (scores 0-2) and high (score
      3) CD47 protein expression were observed in 75% and 25% of AML patients. CD47
      expression significantly correlated with percentage BM blast infiltration and
      peripheral blood blasts. Moreover, high CD47 expression was associated with
      nucleophosmin (NPM1) gene mutations. In contrast, CD47 expression did not
      significantly correlate with overall or progression free survival or response to
      therapy. In summary, a BM TMA permits rapid and reproducible semi-quantitative
      analysis of CD47 protein expression by IHC. While CD47 expression on circulating
      AML blasts has been shown to be a negative prognostic marker for a very defined
      population of AML patients with NK AML, CD47 expression on AML BM blasts is not. 

PMID- 25943032
TI  - Genetic Architecture of Micro-Environmental Plasticity in Drosophila
      melanogaster.
AB  - Individuals of the same genotype do not have the same phenotype for quantitative
      traits when reared under common macro-environmental conditions, a phenomenon
      called micro-environmental plasticity. Genetic variation in micro-environmental
      plasticity is assumed in models of the evolution of phenotypic variance, and is
      important in applied breeding and personalized medicine. Here, we quantified
      genetic variation for micro-environmental plasticity for three quantitative
      traits in the inbred, sequenced lines of the Drosophila melanogaster Genetic
      Reference Panel. We found substantial genetic variation for micro-environmental
      plasticity for all traits, with broad sense heritabilities of the same magnitude
      or greater than those of trait means. Micro-environmental plasticity is not
      correlated with residual segregating variation, is trait-specific, and has
      genetic correlations with trait means ranging from zero to near unity. We
      identified several candidate genes associated with micro-environmental plasticity
      of startle response, including Drosophila Hsp90, setting the stage for future
      genetic dissection of this phenomenon. 

PMID- 25943034
TI  - Social Networks and the Diffusion of Adolescent Problem Behavior: Reliable
      Estimates of Selection and Influence from Sixth Through Ninth Grades.
AB  - Seeking to reduce problematic peer influence is a prominent theme of programs to
      prevent adolescent problem behavior. To support the refinement of this aspect of
      prevention programming, we examined peer influence and selection processes for
      three problem behaviors (delinquency, alcohol use, and smoking). We assessed not
      only the overall strengths of these peer processes, but also their consistency
      versus variability across settings. We used dynamic stochastic actor-based models
      to analyze five waves of friendship network data across sixth through ninth
      grades for a large sample of U.S. adolescents. Our sample included two successive
      grade cohorts of youth in 26 school districts participating in the PROSPER study,
      yielding 51 longitudinal social networks based on respondents' friendship
      nominations. For all three self-reported antisocial behaviors, we found evidence
      of both peer influence and selection processes tied to antisocial behavior. There
      was little reliable variance in these processes across the networks, suggesting
      that the statistical imprecision of the peer influence and selection estimates in
      previous studies likely accounts for inconsistencies in results. Adolescent
      friendship networks play a strong role in shaping problem behavior, but problem
      behaviors also inform friendship choices. In addition to preferring friends with
      similar levels of problem behavior, adolescents tend to choose friends who engage
      in problem behaviors, thus creating broader diffusion.

PMID- 25943036
TI  - Editorial comment: change in leadership.

PMID- 25943035
TI  - In vivo Antimalarial Activity of alpha-Mangostin and the New Xanthone delta
      Mangostin.
AB  - Based on the previously reported in vitro antiplasmodial activity of several
      xanthones from Garcinia mangostana, two xanthones, alpha-mangostin and a new
      compound, delta-mangostin, were isolated from mangosteen husk, and the in vitro
      antiplasmodial and cytotoxic effects were determined. alpha-Mangostin was more
      active against the resistant Plasmodium falciparum chloroquine-resistant (FCR3)
      strain (IC50  = 0.2 +/- 0.01 MUM) than delta-mangostin (IC50  = 121.2 +/- 1.0
      MUM). Furthermore, the therapeutic response according to the administration route
      was evaluated in a Plasmodium berghei malarial murine model. The greatest
      therapeutic response was obtained with intraperitoneal administration; these
      xanthones reduced parasitemia by approximately 80% with a daily dose of 100 mg/kg
      administered twice a day for 7 days of treatment. Neither compound was effective
      by oral administration. Noticeable toxicological effects were not observed. In
      addition to the antimalarial effect of these xanthones isolated from G.
      mangostana husk, the availability of larger amounts of husk raw material to
      purify the bioactive xanthones is advantageous, permitting additional preclinical
      assays or chemical transformations to enhance the biological activity of these
      substances.

PMID- 25943037
TI  - Global surgery - how much of the burden is urological?

PMID- 25943038
TI  - The Neuroprotective Effect of Coumaric Acid on Spinal Cord Ischemia/Reperfusion
      Injury in Rats.
AB  - The main causes of spinal cord ischemia are a variety of vascular pathologies
      causing acute arterial occlusions. We investigated neuroprotective effects of
      coumaric acid on spinal cord ischemia injury in rats. Rats were divided randomly
      into four groups of eight animals as follows: control, ischemia, ischemia +
      coumaric acid, and ischemia + methylprednisolone. In the control group, only a
      laparotomy was performed. In all other groups, the spinal cord ischemia was
      performed by the infrarenal aorta cross-clamping model. Levels of malondialdehyde
      and nuclear respiratory factor 1 were analyzed, as were the activity of
      superoxide dismutase. Histopathological and immunohistochemical evaluations were
      performed. Neurological evaluation was performed with the Tarlov scoring system.
      The ischemia + coumaric acid group was compared with the ischemia group, and a
      significant decrease in malondialdehyde and levels was observed. Nuclear
      respiratory factor 1 level and superoxide dismutase activity of the ischemia +
      coumaric acid group were significantly higher than in the ischemia group. In
      histopathological samples, the ischemia + coumaric acid group is compared with
      the ischemia group, and there was a significant increase in numbers of normal
      neurons. In immunohistochemical staining, hypoxia-inducible factor-1alpha and NF
      kappa B immunopositive neurons were significantly decreased in the ischemia +
      coumaric acid group compared with that in the ischemia group. The neurological
      deficit scores of the ischemia + coumaric acid group were significantly higher
      than the ischemia group at 24 h. Our results revealed for the first time that
      coumaric acid exhibits meaningful neuroprotective activity following ischemia
      reperfusion injury of the spinal cord. 

PMID- 25943039
TI  - (-)-Epicatechin reduces blood pressure increase in high-fructose-fed rats:
      effects on the determinants of nitric oxide bioavailability.
AB  - This work investigated the blood pressure (BP)-lowering effect of the flavanol (
      )-epicatechin in a model of metabolic syndrome. Rats were fed a regular chow diet
      without (Control) or with 10% (w/v) fructose in the drinking water (high
      fructose, HF) for 8 weeks. A subgroup of the HF-fed rats was supplemented with (
      )-epicatechin 20 mg/kg body weight (HF-EC). Dietary (-)-epicatechin reverted the
      increase in BP caused by the fructose treatment. In aorta, superoxide anion
      production and the expression of the NADPH oxidase (NOX) subunits p47(phox) and
      p22(phox) were enhanced in the HF-fed rats. The increase was prevented by (-)
      epicatechin. Similar profile was observed for NOX4 expression. The activity of
      aorta nitric oxide synthase (NOS) was increased in the HF group and was even
      higher in the HF-EC rats. These effects were paralleled by increased endothelial
      NOS phosphorylation at the activation site Ser1177. Among the more relevant
      mitogen-activated protein kinase pathways in vascular tissue, c-Jun-N-terminal
      kinase was shown to be activated in the aorta of the HF-fed rats, and (-)
      epicatechin supplementation mitigated this activation. Thus, the results suggest
      that dietary (-)-epicatechin supplementation prevented hypertension in HF-fed
      rats, decreasing superoxide anion production and elevating NOS activity, favoring
      an increase in NO bioavailability. 

PMID- 25943040
TI  - Cardiac arrest with initial arrest rhythm of pulseless electrical activity: do
      rhythm characteristics correlate with outcome?
AB  - OBJECTIVES: Cardiac arrest is a leading cause of death in the United States, with
      pulseless electrical activity (PEA) as a common initial arrest rhythm. We sought
      to determine if rate of electrical activity and QRS width correlate with survival
      in patients who present with PEA out-of-hospital cardiac arrest. METHODS AND
      RESULTS: This is a retrospective review of patients with PEA out-of-hospital
      cardiac arrest with first documented cardiac rhythm of PEA from January 2010 to
      September 2013. Demographic, arrest and initial rhythm characteristics, and
      patient outcome were abstracted via systematic chart review. The initial 20
      seconds of each rhythm strip were used to ascertain electrical rate and QRS
      width. Primary outcome was survival to hospital discharge. Four hundred fourteen
      patients were eligible for the study. One hundred fifty-two patients did not have
      sufficient data for analysis. Two hundred sixty-two patients were included in the
      final analysis with mean age, 66 years. There were 23 (8.8%) survivors and 17
      (6.5%) neurologically intact survivors. Mean heart rate was 58 (confidence
      interval, 54-63) beats per minute, and mean QRS interval was 100 (confidence
      interval, 95-106) milliseconds. Twenty-nine point seven percent of patients had
      wide QRS complexes, and 70.3% were narrow. There was no difference in survival in
      patients based on heart rate (13.1% vs 7.4%, P = .16) or QRS interval (8.7% vs
      7.7%, P = .79). CONCLUSIONS: In this single emergency medical services agency
      study, neither PEA electrical rate nor QRS width correlated with survival or
      neurologic outcome.

PMID- 25943041
TI  - Recognizing acute appendicitis criteria on abdominal CT: do emergency physicians
      need a preliminary report?
AB  - BACKGROUND: Computed tomography (CT) is invaluable for the diagnosis of acute
      appendicitis (AA) in the emergency setting when used appropriately with proper
      risk stratification. The aim of this study is to investigate the capability and
      accuracy of emergency physicians (EPs) at recognizing AA criteria in intravenous
      contrast-enhanced abdominal CT and to investigate the level of interobserver
      agreement among them. METHODS: Consecutive patients who presented to Izmir
      University Hospital from January 1, 2014, to December 31, 2014, were evaluated.
      Patients with histopathologically confirmed AA and had intravenous contrast
      enhanced abdominal CT were enrolled. Abdominal CT were interpreted by 4 EPs in a
      blind fashion. To compare differences in performances between observers,
      sensitivity, specificity, positive predictive value, negative predictive value,
      and kappa values were calculated. The results were then compared with the
      radiology department's official reports. RESULTS: There were 48 patients eligible
      for the study. Among these patients, 19 were male (41%), with a mean age of 34.4
      years (+/-11.3 years). Five patients were CT-negative appendicitis according to
      official radiology reports that were accepted as the criterion standard. The best
      sensitivity and negative predictive values were achieved at criterion
      "enlargement of the appendix," whereas the least sensitivity was for criterion
      "lack of opacification in an enlarged appendix." CONCLUSIONS: The recognition of
      the CT criteria for AA among EPs is substantial at best, and their ability to
      recognize the primary criteria for diagnosing AA is good. Emergency physicians
      have to gain a higher level of expertise to use this invaluable diagnostic tool
      more efficiently.

PMID- 25943042
TI  - National trends in resource utilization associated with ED visits for syncope.
AB  - BACKGROUND: Over the last 20 years, numerous research articles and clinical
      guidelines aimed at optimizing resource utilization for emergency department (ED)
      patients presenting with syncope have been published. HYPOTHESIS: We hypothesized
      that there would be temporal trends in syncope-related ED visits and associated
      trends in imaging, hospital admissions, and diagnostic frequencies. METHODS: The
      ED component of National Hospital Ambulatory Medical Care Survey was analyzed
      from 2001 through 2010, comprising more than 358000 visits (representing an
      estimated 1.18 billion visits nationally). We selected ED visits with a reason
      for visit of syncope or fainting and calculated nationally representative
      weighted estimates for prevalence of such visits and associated rates of advanced
      imaging utilization and admission. For admitted patients from 2005 to 2010, the
      most frequent hospital discharge diagnoses were tabulated. RESULTS: During the
      study period, there were more than 3500 actual ED visits (representing 11.9
      million visits nationally) related to syncope, representing roughly 1% of all ED
      visits. Admission rates for syncope patients ranged from 27% to 35% and showed no
      significant downward trend (P = .1). Advanced imaging rates increased from about
      21% to 45% and showed a significant upward trend (P < .001). For admitted
      patients, the most common hospital discharge diagnosis was the symptomatic
      diagnosis of "syncope and collapse" (36.4%). CONCLUSIONS: Despite substantial
      efforts by medical researchers and professional societies, resource utilization
      associated with ED visits for syncope appears to have actually increased. There
      have been no apparent improvements in diagnostic yield for admissions. Novel
      strategies may be needed to change practice patterns for such patients.

PMID- 25943043
TI  - Septic Pulmonary Embolism Caused by Internal Shunt Infection.

PMID- 25943044
TI  - Characterization of Novel Family IV Esterase and Family I.3 Lipase from an Oil
      Polluted Mud Flat Metagenome.
AB  - Two genes encoding lipolytic enzymes were isolated from a metagenomic library
      constructed from oil-polluted mud flats. An esterase gene, est3K, encoded a
      protein of 299 amino acids (ca. 32,364 Da). Est3K was a family IV esterase with
      typical motifs, HGGG, and HGF. Although est3K showed high identity to many genes
      with no information on their enzymatic properties, Est3K showed the highest
      identity (36 %) to SBLip5.1 from forest soil metagenome when compared to the
      enzymes with reported properties. A lipase gene, lip3K, encoded a protein of 616
      amino acids (ca. 64,408 Da). Lip3K belonged to family I.3 lipase with a C
      terminal secretion signal and showed the highest identity (93 %) to the lipase of
      Pseudomonas sp. MIS38. The presence of several newly identified conserved motifs
      in Est3K and Lip3K are suggested. Both Est3K and Lip3K exerted their maximal
      activity at pH 9.0 and 50  degrees C. The activity of Lip3K was significantly
      increased by the presence of 30 % methanol. The ability of the enzymes to retain
      activities in the presence of methanol and the substrates may offer a merit to
      the biotechnological applications of the enzymes such as transesterification. The
      activity and the thermostability of Lip3K were increased by Ca(2+). Est3K and
      Lip3K preferred p-nitrophenyl butyrate (C4) and octanoate (C8), respectively, as
      the substrate and acted independently on the substrates with no synergistic
      effect. 

PMID- 25943045
TI  - Laminoplasty with adjunct anterior short segment fusion for multilevel cervical
      myelopathy associated with local kyphosis.
AB  - BACKGROUND: When treating patients who have multilevel cervical spondylotic
      myelopathy (MCSM) with short-segment kyphosis, instability, or major anterior
      foci, long-level anterior decompression with fusion is often a standard method
      but can cause obvious loss of range of motion and usually needs further posterior
      stabilization. For MCSM with correctable kyphosis or simple instability,
      laminectomy with lateral-mass instrumented fusion is also a treatment of choice,
      but all the involved segments are immobilized. Combining expansive open-door
      laminoplasty (EOLP) and anterior short-segment fusion may be an alternative
      treatment to save more motion segments. METHODS: This study included 109 patients
      who exhibited MCSM with combined local kyphosis, instability, and anterior
      pathology, and received EOLP and concomitant anterior short-segment fusion. The
      patients were enrolled from August 2005 to July 2012. Nurick scores and Japanese
      Orthopedics Association cervical myelopathy scores were used to evaluate the
      functional outcomes. Follow-up plain films were collected and magnetic resonance
      imaging was conducted to assess the radiographic outcomes. RESULTS: One year
      after the operation, the Japanese Orthopedics Association recovery rate was 83.4
      +/- 16.6%. The improvement in the functional scores and decrease in neck pain
      were significant. The canal width improved without further collapse at 12 months.
      The preservation of range of motion was approximately 57% at 1 year. CONCLUSION:
      EOLP with adjunct anterior short-segment decompression fusion yields an excellent
      outcome for MCSM patients who exhibit concomitant short-segment kyphosis,
      instability or major anterior pathology. Performing laminoplasty first is safer
      for the spinal cord due to its posterior shifting while anterior procedures are
      being done.

PMID- 25943046
TI  - Improvement of regressive autism symptoms in a child with TMLHE deficiency
      following carnitine supplementation.
AB  - Disorders of carnitine biosynthesis have recently been associated with
      neurodevelopmental syndromes such as autism spectrum disorder (ASD). A 4-year-old
      male with autism and two episodes of neurodevelopmental regression was identified
      to have a mutation in the TMLHE gene, which encodes the first enzyme in the
      carnitine biosynthesis pathway, and concurrent carnitine deficiency. Following
      carnitine supplementation, the patient's regression ended, and the boy started
      gaining developmental milestones. This case report suggests that deficits in
      carnitine biosynthesis may be responsible for some cases of regression in
      individuals with ASD, and that testing for the respective biochemical pathway
      should be considered. Furthermore, this case suggests that carnitine
      supplementation may be useful in treating (and potentially preventing) regressive
      episodes in patients with carnitine deficiency. Further work to better define the
      role of disorders of carnitine biosynthesis in autism spectrum disorder is
      warranted.

PMID- 25943047
TI  - Hb Cervantes, Hb Maranon, Hb La Mancha and Hb Goya: Description of 4 new
      haemoglobinopathies.
AB  - OBJECTIVES: alpha-thalassemias are caused by a deficiency in or absence of
      synthesis of the alpha-chain of haemoglobin (Hb). In contrast, structural
      haemoglobinopathies are due to mutations that change the amino acid sequence of
      the protein chain. We report 4 newly identified alpha-chain Hb variants. Two
      variants were hyper-unstable, whereas the other 2 were structural variants with
      an altered electrophoretic mobility. DESIGN AND METHODS: The first 2 families
      were identified because of microcytosis and hypochromia with a normal Hb A2 and
      Hb F but without iron deficiency. The other 2 families came to scrutiny because
      of a peak of abnormal Hb during routine analytical assays. These Hb variants were
      characterized by specific sequencing. RESULTS: The hyper-instability of Hb
      Cervantes is probably due to its lower affinity for the alpha chain haemoglobin
      stabilizing protein (AHSP). Hb Maranon is another unstable Hb variant that
      produces an alpha-thalassemia phenotype. For the identification of Hb La Mancha,
      a molecular characterization by sequencing was required. Finally, Hb Goya was
      found to have the same electrophoretic mobility as Hb J. A lower percentage of
      the variant was obtained due to a possible component of instability, though the
      patient did not show evidence of anaemia. CONCLUSION: These variants of Hb add to
      the variety and complexity of disorders of the genes that encode Hb.

PMID- 25943048
TI  - [Perforating keratoplasty versus Descemet stripping automated endothelial
      keratoplasty in the partner eye: Functional results and patient satisfaction].
AB  - BACKGROUND: This study compared the postoperative results and patient
      satisfaction between penetrating keratoplasty (PK) and Descemet stripping
      automated endothelial keratoplasty (DSAEK) in patients who underwent PK in one
      eye and DSAEK in the other eye. METHODS: A total of 15 patients were identified
      from the corneal database register and the medical charts were analyzed for best
      corrected visual acuity (BCVA), keratometric astigmatism, endothelial cell
      density and postoperative complications. Patient satisfaction was evaluated by a
      standardized interview. RESULTS: Median follow-up time for PK was 55 months and
      18 months for DSAEK (p < 0.01). Median BCVA in PK was 0.8 and 0.5 in DSAEK (p =
      0.01) at the end of follow-up. Median keratometric astigmatism was 3.1 diopters
      after PK and 1.9 diopters after DSAEK (p = 0.2). Median endothelial cell density
      was 831 cells/mm(2) after PK and 860 cells/mm(2) after DSAEK (p = 0.63). For the
      interventions 57 % of the patients preferred PK, 36 % preferred DSAEK and 7 %
      were undecided. Patients assigned the better performing eye to the PK side in 64
      % and in 29 % to the DSAEK side and 7 % perceived equal visual performance in
      both eyes. CONCLUSION: The results leave doubt about the superiority of DSAEK
      compared to PK; however, exceptionally good refractive results of the 15 PK eyes
      analyzed and significantly longer follow-up times after PK could be the reason
      for the unexpectedly high patient preference for PK.

PMID- 25943049
TI  - [Adenoviral keratoconjunctivitis].
AB  - Keratoconjunctivitis caused by adenoviruses (epidemic keratoconjunctivitis, EKC,
      ICD-10 B30.0+) is common, can be severe and may cause significant morbidity. In
      the early stages of adenoviral infections it is often difficult to differentiate
      the clinical presentation from other causes of a red eye. Because of its highly
      contagious nature that can rapidly lead to epidemic outbreaks, prompt viral
      identification and prevention of further spread are major challenges. Even today
      the diagnosis is still mainly clinical, with laboratory tests only rarely
      contributing. New diagnostic tests, such as the Rapid Pathogen Detector (RPS,
      Sarasota FL) AdenoPlus detection kit, that are practical, rapid and inexpensive
      to use in the general practice may obviate these problems. Because of its highly
      resistant properties to desiccation and highly developed escape mechanisms which
      protect the virus from the host's immune response, long-term problems often
      remain. Remnants of viral proteins often persist on the corneal surface of
      Bowman's layer for a long time and may lead to the formation of subepithelial
      infiltrates. No treatment other than symptomatic eye drops is available. The
      major sequelae are subepithelial infiltrates, which are difficult to treat.
      Cyclosporin A eye drops are a good option with a low risk profile. The use of
      topical steroids can possibly be disadvantageous but can be discussed at all
      stages of the disease. As nosocomial spread of adenoviruses is relatively common,
      preventive measures remain a major responsibility for ophthalmologists. 

PMID- 25943050
TI  - A Comparison of Three Methods to Increase Scleral Contact Lens On-Eye Stability.
AB  - PURPOSE: To quantify on-eye rotational and translational stability of three
      scleral contact lens stabilization methods and to model the variation in visual
      acuity when these movements occur in a wavefront-guided correction for highly
      aberrated eyes. METHODS: Three lens stabilization methods were integrated into
      the posterior periphery of a scleral contact lens designed at the Visual Optics
      Institute. For comparison, a lens with no stabilization method (rotationally
      symmetric posterior periphery) was designed. The lenses were manufactured and
      lens movements were quantified on 8 eyes as the average SD of the observed
      translations and rotations over 60 min of wear. In addition, the predicted
      changes in acuity for five eyes with keratoconus wearing a simulated wavefront
      guided correction (full correction through the fifth order) were modeled using
      the measured movements. RESULTS: For each lens design, no significant differences
      in the translation and rotation were found between left and right eyes, and
      lenses behaved similarly on all subjects. All three designs with peripheral
      stability modifications exhibited no statistically significant differences in
      translation and rotation distributions of lens movement and were statistically
      more stable than the spherical lens in rotation. When the measured movements were
      used to simulate variation in visual performance, the 3 lenses with integrated
      stability methods showed a predicted average loss in acuity from the perfectly
      aligned condition of approximately 0.06 logMAR (3 letters), compared with the
      loss of over 0.14 logMAR (7 letters) for the lens with the spherical periphery.
      CONCLUSION: All three stabilization methods provided superior stability, as
      compared with the spherical lens design. Simulations of the optical and visual
      performance suggest that all three stabilization designs can provide desirable
      results when used in the delivery of a wavefront-guided correction for a highly
      aberrated eye.

PMID- 25943051
TI  - Symptoms and Signs in Rigid Gas Permeable Lens Wearers During Adaptation Period.
AB  - OBJECTIVES: To evaluate neophyte contact lens wearers' fitting to rigid gas
      permeable (RGP) contact lenses in terms of wearing time, tear volume, stability,
      corneal staining, and subjective ratings, over a 1-month period of time. METHODS:
      Twenty-two young healthy subjects were enrolled for wearing RGP on a daily wear
      basis. The participants included in this study never wore contact lenses and
      showed a value under 10 in McMonnies Questionnaire. Contact Lens Dry Eye
      Questionnaire, Visual Analog Scales, Schirmer test, tear film break-up time
      (BUT), and corneal staining grading were performed. Follow-up visits were
      scheduled at 1, 7, 15, and 28 days. RESULTS: Six subjects dropped out due to
      discomfort from the study before 1 month (27% of discontinuation rate).
      Successful RGP wearers (16 participants) achieved high levels of subjective
      vision and reported comfort scores of approximately 9 of 10 between 10 and 15
      days. They reported wearing their lenses for an average of 10.12+/-2.43 hr after
      1 month of wear. Conversely, unsuccessful wearers discontinued wearing the lenses
      after the first 10 to 15 days, showing comfort scores and wearing time
      significantly lower compared with the first day of wear. Schirmer test showed a
      significant increase at 10 days (P<0.001), and the BUT trends decreased after the
      first week of wear in unsuccessful group. CONCLUSIONS: Symptomatology related
      with dryness and discomfort, detected during the first 10 days of the adaptation,
      may help the clinician to predict those participants who will potentially fail to
      adapt to RGP lens wear.

PMID- 25943053
TI  - Little Stars.

PMID- 25943052
TI  - Cancer immunotherapy: enthusiasm and reality aligning at last.

PMID- 25943054
TI  - Mobile medicine.

PMID- 25943055
TI  - Terminal cancer: a happy ending?

PMID- 25943056
TI  - Recalibrating emergency care in the UK: pulling our weight.

PMID- 25943057
TI  - Should patients with melanoma brain metastases receive adjuvant whole-brain
      radiotherapy?

PMID- 25943058
TI  - Radiotherapy for elderly patients with low-risk breast cancer.

PMID- 25943059
TI  - PET-adapted salvage therapy for Hodgkin's lymphoma.

PMID- 25943060
TI  - PET-adapted salvage therapy for Hodgkin's lymphoma--authors' reply.

PMID- 25943061
TI  - Correction to Lancet Oncol 2015; 16: e163.

PMID- 25943062
TI  - Correction to Lancet Oncol 2015; 16: 545.

PMID- 25943063
TI  - Correction to Lancet Oncol 2013; 14: e374.

PMID- 25943064
TI  - Correction to Lancet Oncol 2015; 16: 447, 448.

PMID- 25943065
TI  - Present status of human papillomavirus vaccine development and implementation.
AB  - Oncogenic human papillomavirus (HPV) infection is the cause of nearly all
      cervical cancers and a proportion of other anogenital and oropharyngeal cancers.
      A bivalent vaccine containing HPV 16 and 18 and a quadrivalent vaccine containing
      HPV 6, 11, 16, and 18 antigens are in use in vaccination programmes around the
      world. In clinical trials, three vaccine doses provided 90-100% protection
      against cervical infection and pre-cancer related to HPV 16 and 18 in women aged
      15-26 years who were not infected at vaccination. Partial cross-protection
      against other HPV types has been reported but its duration is unknown. The
      vaccines were also efficacious at the prevention of HPV 16 and 18 infections at
      other anatomical sites in both sexes. Immunobridging studies allowed licensing of
      the vaccines for use starting at age 9 years for both sexes. Two-dose schedules
      elicit high antibody concentrations, leading to the recommendation of two-dose
      schedules for girls aged 9-14 years. Pre-licensure and post-licensure studies
      have provided data supporting vaccine safety. In 2014, a nonavalent vaccine
      containing HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 antigens was licensed by the
      US Food and Drug Administration. HPV vaccination was first introduced in high
      income countries owing to vaccine cost, logistic challenges, and competing health
      priorities. Since 2011, vaccine prices have lowered, allowing the introduction of
      the vaccine in some middle-income countries. Funding of the vaccine by the GAVI
      Alliance in 2012 led to demonstration projects in some low-income countries. By
      2014, more than 57 countries had included the HPV vaccine in their national
      health programmes. Data from several countries have shown the effect of
      vaccination on HPV infection and associated disease, and provided evidence of
      herd immunity. Expansion of programmes to countries with the highest burden of
      disease is beginning, but further efforts are needed to realise the potential of
      HPV vaccines. 

PMID- 25943066
TI  - Next generation prophylactic human papillomavirus vaccines.
AB  - The two licensed bivalent and quadrivalent human papillomavirus (HPV) L1 (the
      major papillomavirus virion protein) virus-like particle (VLP) vaccines are
      regarded as safe, effective, and well established prophylactic vaccines. However,
      they have some inherent limitations, including a fairly high production and
      delivery cost, virus-type restricted protection, and no reported therapeutic
      activity, which might be addressed with the development of alternative dosing
      schedules and vaccine products. A change from a three-dose to a two-dose protocol
      for the licensed HPV vaccines, especially in younger adolescents (aged 9-13
      years), is underway in several countries and is likely to become the future norm.
      Preliminary evidence suggests that recipients of HPV vaccines might derive
      prophylactic benefits from one dose of the bivalent vaccine. Substantial interest
      exists in both the academic and industrial sectors in the development of second
      generation L1 VLP vaccines in terms of cost reduction-eg, by production in
      Escherichia coli or alternative types of yeast. However, Merck's nonavalent
      vaccine, produced via the Saccharomyces cerevisiae production system that is also
      used for their quadrivalent vaccine, is the first second-generation HPV VLP
      vaccine to be available on the market. By contrast, other pharmaceutical
      companies are developing microbial vectors that deliver L1 genes. These two
      approaches would add an HPV component to existing live attenuated vaccines for
      measles and typhoid fever. Prophylactic vaccines that are based on induction of
      broadly cross-neutralising antibodies to L2, the minor HPV capsid protein, are
      also being developed both as simple monomeric fusion proteins and as virus-like
      display vaccines. The strong interest in developing the next generation of
      vaccines, particularly by manufacturers in middle-to-high income countries,
      increases the likelihood that vaccine production will become decentralised with
      the hope that effective HPV vaccines will be made increasingly available in low
      resource settings where they are most needed. 

PMID- 25943067
TI  - Primary endpoints for future prophylactic human papillomavirus vaccine trials:
      towards infection and immunobridging.
AB  - Although available human papillomavirus (HPV) vaccines have high efficacy against
      incident infection and disease caused by HPV types that they specifically target,
      new vaccine trials continue to be needed. The goals of these trials could include
      change of vaccine dose or route of administration (or both), development of
      second-generation vaccines, and the regional manufacture of biosimilar vaccines.
      We summarise present thinking about primary endpoints for HPV vaccine trials as
      developed at an experts workshop convened by the International Agency for
      Research on Cancer and the US National Cancer Institute in September, 2013.
      Efficacy trials that have led to licensure for cervical cancer prevention have
      used the disease endpoint of cervical intraepithelial neoplasia grade 2 or worse
      (CIN2+). However, on the basis of experience from the trials and present
      knowledge of HPV infection, future efficacy trials for new vaccines can be safely
      streamlined by the use of persistent HPV infection, which occurs more frequently
      than CIN2+, and can be more reproducibly measured as a primary endpoint.
      Immunobridging trials can be sufficient to ascertain immunological non
      inferiority for licensure for alternate dosing schedules, bridging to age 26
      years or younger, and biosimilar vaccines, with post-licensure surveillance
      confirming effectiveness. These recommendations are intended to help stimulate
      continued vaccine development while ensuring appropriate assessment of safety and
      efficacy. 

PMID- 25943068
TI  - Programmed cell death-1 inhibition in lymphoma.
AB  - Cancers can evade the host immune system by inducing upregulation of immune
      inhibitory signals. Anti-programmed cell death-1 (PD-1) monoclonal antibodies
      block these inhibitory signals allowing the host to mount an immune response
      against malignant cells. This class of drugs is active in solid tumours, where
      upregulation of cell-surface PD-1 ligand proteins is nearly uniform. Because
      lymphoma is a malignancy of immune system cells, the role of the PD-1 pathway in
      these neoplasms is more complex. However, early clinical trials using PD-1
      inhibitors have shown significant clinical activity in various subtypes of
      relapsed lymphoma. In this Review, we assess the scientific literature on the
      role of the PD-1 pathway in lymphoma, the relevant clinical data for PD-1
      inhibition, and future strategies for this next generation of anticancer agents. 

PMID- 25943069
TI  - Tackling cancer control in the Gulf Cooperation Council Countries.
AB  - Cancer is a major health problem in both high income and middle-to-low income
      countries, and is the second leading cause of death in the world. Although more
      than a third of cancer could be prevented and another third could be cured if
      diagnosed early, it remains a huge challenge to health-care systems worldwide.
      Despite substantial improvements in health services some of the countries in the
      Gulf region, the burden of non-communicable diseases is a major threat, primarily
      due to the rapid socioeconomic shifts that have led to unfavourable changes in
      lifestyle such as increased tobacco use, decreased physical activity, and
      consumption of unhealthy food. In the Gulf Cooperation Council states (United
      Arab Emirates, Bahrain, Saudi Arabia, Oman, Qatar, and Kuwait), advanced breast
      cancer, colorectal cancer, leukaemia, thyroid cancer, and non-Hodgkin lymphomas
      are the most common cancers affecting younger populations compared with other
      countries. By contrast with cancer prevalence in developed countries, prostate,
      lung, and cervical cancers are not among the most common cancers in the Gulf
      region. In view of the increased cost of cancer management worldwide, integrated
      approaches between primary, secondary, and tertiary health-care systems with
      special focus on prevention and early detection is an essential step in the
      countries' efforts in the fight against cancer.

PMID- 25943071
TI  - Preparation, cytotoxicity and in vivo bioimaging of highly luminescent water
      soluble silicon quantum dots.
AB  - Designing various inorganic nanomaterials that are cost effective, water soluble,
      optically photostable, highly fluorescent and biocompatible for bioimaging
      applications is a challenging task. Similar to semiconducting quantum dots (QDs),
      silicon QDs are another alternative and are highly fluorescent, but non-water
      soluble. Several surface modification strategies were adopted to make them water
      soluble. However, the photoluminescence of Si QDs was seriously quenched in the
      aqueous environment. In this report, highly luminescent, water-dispersible, blue-
      and green-emitting Si QDs were prepared with good photostability. In vitro
      studies in monocytes reveal that Si QDs exhibit good biocompatibility and
      excellent distribution throughout the cytoplasm region, along with the
      significant fraction translocated into the nucleus. The in vivo zebrafish studies
      also reveal that Si QDs can be evenly distributed in the yolk-sac region.
      Overall, our results demonstrate the applicability of water-soluble and highly
      fluorescent Si QDs as excellent in vitro and in vivo bioimaging probes. 

PMID- 25943072
TI  - The phase diagram and hardness of carbon nitrides.
AB  - Novel superhard materials, especially those with superior thermal and chemical
      stability, are needed to replace diamond. Carbon nitrides (C-N), which are likely
      to possess these characteristics and have even been expected to be harder than
      diamond, are excellent candidates. Here we report three new superhard and
      thermodynamically stable carbon nitride phases. Based on a systematic
      evolutionary structure searches, we report a complete phase diagram of the C-N
      system at 0-300 GPa and analyze the hardest metastable structures. Surprisingly,
      we find that at zero pressure, the earlier proposed graphitic-C3N4 structure ()
      is dynamically unstable, and we find the lowest-energy structure based on s
      triazine unit and s-heptazine unit. 

PMID- 25943073
TI  - Lactobacillus fermentum AGR1487 cell surface structures and supernatant increase
      paracellular permeability through different pathways.
AB  - Lactobacillus fermentum is commonly found in food products, and some strains are
      known to have beneficial effects on human health. However, our previous research
      indicated that L. fermentum AGR1487 decreases in vitro intestinal barrier
      integrity. The hypothesis was that cell surface structures of AGR1487 are
      responsible for the observed in vitro effect. AGR1487 was compared to another
      human oral L. fermentum strain, AGR1485, which does not cause the same effect.
      The examination of phenotypic traits associated with the composition of cell
      surface structures showed that compared to AGR1485, AGR1487 had a smaller genome,
      utilized different sugars, and had greater tolerance to acid and bile. The effect
      of the two strains on intestinal barrier integrity was determined using two
      independent measures of paracellular permeability of the intestinal epithelial
      Caco-2 cell line. The transepithelial electrical resistance (TEER) assay
      specifically measures ion permeability, whereas the mannitol flux assay measures
      the passage of uncharged molecules. Both live and UV-inactivated AGR1487
      decreased TEER across Caco-2 cells implicating the cell surfaces structures in
      the effect. However, only live AGR1487, and not UV-inactivated AGR1487, increased
      the rate of passage of mannitol, implying that a secreted component(s) is
      responsible for this effect. These differences in barrier integrity results are
      likely due to the TEER and mannitol flux assays measuring different
      characteristics of the epithelial barrier, and therefore imply that there are
      multiple mechanisms involved in the effect of AGR1487 on barrier integrity.

PMID- 25943075
TI  - Poland's syndrome: a concise review of the clinical features highlighting
      associated dermatologic manifestations.
AB  - Poland's syndrome is a rare congenital condition characterized by absence of the
      pectoralis major muscle and a wide spectrum of associated ipsilateral chest wall
      and upper extremity anomalies. Associated dermatologic anomalies classically
      include pectoral and axillary alopecia, anhidrosis due to the absence of sweat
      glands, and deficiency in subcutaneous fat. Functional limitations are minimal,
      and thus surgical correction is primarily indicated for aesthetic purposes. Chest
      wall reconstruction typically involves transposition of a latissimus dorsi
      myocutaneous flap with or without a temporary subcutaneous tissue expander prior
      to surgical reconstruction. Using the PubMed database, a literature review was
      done on Poland's syndrome. We summarize the key features of Poland's syndrome,
      including the epidemiology, clinical presentation, pathogenesis, and management,
      and highlight the dermatologic associations reported in the literature. 

PMID- 25943074
TI  - Cervical cancer screening in low-resource settings: A cost-effectiveness
      framework for valuing tradeoffs between test performance and program coverage.
AB  - As cervical cancer screening programs are implemented in low-resource settings,
      protocols are needed to maximize health benefits under operational constraints.
      Our objective was to develop a framework for examining health and economic
      tradeoffs between screening test sensitivity, population coverage and follow-up
      of screen-positive women, to help decision makers identify where program
      investments yield the greatest value. As an illustrative example, we used an
      individual-based Monte Carlo simulation model of the natural history of human
      papillomavirus (HPV) and cervical cancer calibrated to epidemiologic data from
      Uganda. We assumed once in a lifetime screening at age 35 with two-visit HPV DNA
      testing or one-visit visual inspection with acetic acid (VIA). We assessed the
      health and economic tradeoffs that arise between (i) test sensitivity and
      screening coverage; (ii) test sensitivity and loss to follow-up (LTFU) of screen
      positive women; and (iii) test sensitivity, screening coverage and LTFU
      simultaneously. The decline in health benefits associated with sacrificing HPV
      DNA test sensitivity by 20% (e.g., shifting from provider- to self-collection of
      specimens) could be offset by gains in coverage if coverage increased by at least
      20%. When LTFU was 10%, two-visit HPV DNA testing with 80-90% sensitivity was
      more effective and more cost-effective than one-visit VIA with 40% sensitivity
      and yielded greater health benefits than VIA even as VIA sensitivity increased to
      60% and HPV test sensitivity declined to 70%. As LTFU increased, two-visit HPV
      DNA testing became more costly and less effective than one-visit VIA. Setting
      specific data on achievable test sensitivity, coverage, follow-up rates and
      programmatic costs are needed to guide decision making for cervical cancer
      screening. 

PMID- 25943076
TI  - Quantitative Evaluation of the Total Magnetic Moments of Colloidal Magnetic
      Nanoparticles: A Kinetics-based Method.
AB  - A kinetics-based method is proposed to quantitatively characterize the collective
      magnetization of colloidal magnetic nanoparticles. The method is based on the
      relationship between the magnetic force on a colloidal droplet and the movement
      of the droplet under a gradient magnetic field. Through computational analysis of
      the kinetic parameters, such as displacement, velocity, and acceleration, the
      magnetization of colloidal magnetic nanoparticles can be calculated. In our
      experiments, the values measured by using our method exhibited a better linear
      correlation with magnetothermal heating, than those obtained by using a vibrating
      sample magnetometer and magnetic balance. This finding indicates that this method
      may be more suitable to evaluate the collective magnetism of colloidal magnetic
      nanoparticles under low magnetic fields than the commonly used methods. Accurate
      evaluation of the magnetic properties of colloidal nanoparticles is of great
      importance for the standardization of magnetic nanomaterials and for their
      practical application in biomedicine. 

PMID- 25943077
TI  - Atherogenesis and inflammation. From cellular mediators to regulatory mechanisms
      of inflammation in atherosclerosis.

PMID- 25943078
TI  - [Haemostatic aspects in clinical oncology].
AB  - The clinical link between cancer and thrombosis has been recognized by Armand
      Trousseau in 1865. It has become clear that activation of coagulation and
      fibrinolysis plays an important role not only in the pathophysiology of
      Trousseau's syndrome, but also in the progression of solid malignancies. In
      particular, tissue factor is critical for both primary tumour growth and
      haematogenous metastasis. Haemostatic perturbations in cancer patients are, at
      least in part, controlled by defined genetic events in molecular tumourigenesis,
      including activating and inactivating mutations of oncogenes and tumour
      suppressor genes, respectively. While long-term treatment with low-molecular
      weight heparin (LMWH) is considered standard therapy for established venous
      thromboembolism (VTE), pharmacological VTE prophylaxis in ambulatory cancer
      patients and the management of complex systemic coagulopathies remain a challenge
      and have to be decided on an individual basis and in a risk-adapted manner.
      Experimental and preclinical studies further suggest that LMWH may be beneficial
      in cancer therapy, but this innovative concept has not yet been proven beyond
      doubt in rigorously designed clinical trials. 

PMID- 25943079
TI  - Linking mechanistic toxicology to population models in forecasting recovery from
      chemical stress: A case study from Jackfish Bay, Ontario, Canada.
AB  - Recovery of fish and wildlife populations after stressor mitigation serves as a
      basis for evaluating remediation success. Unfortunately, effectively monitoring
      population status on a routine basis can be difficult and costly. In the present
      study, the authors describe a framework that can be applied in conjunction with
      field monitoring efforts (e.g., through effects-based monitoring programs) to
      link chemically induced alterations in molecular and biochemical endpoints to
      adverse outcomes in whole organisms and populations. The approach employs a
      simple density-dependent logistic matrix model linked to adverse outcome pathways
      (AOPs) for reproductive effects in fish. Application of this framework requires a
      life table for the organism of interest, a measure of carrying capacity for the
      population of interest, and estimation of the effect of stressors on vital rates
      of organisms within the study population. The authors demonstrate the framework
      using linked AOPs and population models parameterized with long-term monitoring
      data for white sucker (Catostomus commersoni) collected from a study site at
      Jackfish Bay, Lake Superior, Canada. Individual responses of fish exposed to pulp
      mill effluent were used to demonstrate the framework's capability to project
      alterations in population status, both in terms of ongoing impact and subsequent
      recovery after stressor mitigation associated with process changes at the mill.
      The general approach demonstrated at the Jackfish Bay site can be applied to
      characterize population statuses of other species at a variety of impacted sites
      and can account for effects of multiple stressors (both chemical and nonchemical)
      and dynamics within complex landscapes (i.e., meta-populations including
      emigration and immigration processes).

PMID- 25943080
TI  - Validation of the Roland Morris Questionnaire in Colombia to Evaluate Disability
      in Low Back Pain.
AB  - STUDY DESIGN: An observational study was performed to validate a scale.
      OBJECTIVE: This study validated the Roland Morris Questionnaire (RMQ) in
      Colombia. SUMMARY OF BACKGROUND DATA: The RMQ is a frequently used instrument for
      the evaluation of disability in patients with low back pain. The psychometric
      properties of the RMQ are highly reliable, but a validated version is not
      available in our country. METHODS: The RMQ 24-item scale ranges from 0 (no
      disability) to 24 (maximum disability) and it was applied to 133 patients older
      than 18 years of age with low back pain of any etiology and duration.
      Reliability, validity of content, construct and criterion were evaluated, and the
      latter was compared with the Oswestry Disability Index 2.1a, SF-36, and the
      visual analogue scale. Sensitivity to change was evaluated in patients with
      subacute low back pain, and a pharmacological and/or physical rehabilitation
      intervention was performed and the effect size of the treatment was calculated
      with Cohen's d coefficient. RESULTS: The patients' average age was 43.4 (16.3)
      years, out of which 67.7% were females. Internal consistency revealed a
      coefficient of Cronbach's alpha of 0.86. Intraobserver reliability revealed an
      intraclass correlation coefficient of 0.92. Construct validity between acute and
      chronic patients showed no significant differences (P = 0.405). Concurrent
      criterion validity compared with the Oswestry Disability Index 2.1a revealed a
      Pearson correlation coefficient of 0.745 which is a very good correlation. The
      correlation between RMQ and SF-36 was significant. The Pearson correlation
      between the RMQ and visual analogue scale was r = 0.438 with a P < 0.005.
      Sensitivity to change had a Cohen's d coefficient of 1.27, which corresponds to a
      very large effect size. CONCLUSION: The RMQ is a useful and reliable instrument
      for the evaluation of patients with low back pain, and it allows an adequate
      clinical postintervention follow-up. LEVEL OF EVIDENCE: 3.

PMID- 25943081
TI  - A Biomechanical Assessment of Kyphoplasty as a Stand-Alone Treatment in a Human
      Cadaveric Burst Fracture Model.
AB  - STUDY DESIGN: In vitro biomechanics study. OBJECTIVE: To determine whether
      kyphoplasty is an adequate stand-alone treatment for restoring biomechanical
      stability in the spine after experiencing high-energy vertebral burst fractures.
      SUMMARY OF BACKGROUND DATA: Kyphoplasty in the treatment of high-energy vertebral
      burst fractures has been shown by previous studies to significantly improve
      stiffness when used in conjunction with pedicle screw instrumentation. However,
      it is not known whether kyphoplasty as a stand-alone treatment may be an
      acceptable method for restoring biomechanical stability of a spinal motion
      segment post-burst fracture while allowing flexibility of the motion segment
      through the intervertebral discs. METHODS: Young cadaveric spines (15-50 yr old;
      3 males and 1 female; bone mineral density 0.27-0.31 gHA/cm) were divided into
      motion segments consisting of 3 intact vertebrae separated by 2 intervertebral
      discs (T11-L1 and L2-L4). Mechanical testing in axial, flexion/extension, lateral
      bending, and torsion was performed on each specimen in an intact state, after an
      experimentally simulated burst fracture and postkyphoplasty. Computed tomography
      was used to confirm the burst fractures and quantify cement placement. RESULTS:
      Between the intact and burst-fractured states significant decreases in stiffness
      were seen in all loading modes (63%-69%). Burst fracture increased the average
      angulation of the vertebral endplates 147% and decreased vertebral body height by
      an average of 40%. Postkyphoplasty, only small recoveries in stiffness were seen
      in axial, flexion/extension, and lateral bending (4%-12%), with no improvement in
      torsional stiffness. Large angular deformations (85%) and height loss (31%)
      remained postkyphoplasty as compared with the intact state. CONCLUSION: Lack of
      overall improvement in biomechanical stiffness indicates failure of kyphoplasty
      to sufficiently restore stability as a stand-alone treatment after high-energy
      burst fracture. The lack of stability can be explained by an inability to
      biomechanically repair the compromised intervertebral discs. LEVEL OF EVIDENCE:
      3.

PMID- 25943082
TI  - Three-Dimensional Computed Tomography-Based Specimen-Specific Kinematic Model for
      Ex Vivo Assessment of Lumbar Neuroforaminal Space.
AB  - STUDY DESIGN: Cadaveric study to accurately measure lumbar neuroforaminal area
      and height throughout the flexion-extension range of motion (ROM). OBJECTIVE:
      Create a new computed tomography (CT)-based specimen-specific model technique to
      provide insight on the effects of kinematics on lumbar neuroforamen morphology
      during flexion-extension ROM. SUMMARY OF BACKGROUND DATA: Nerve root compression
      is a key factor in symptomatic progression of degenerative disc disease because
      these changes directly affect neuroforaminal area. Traditional techniques to
      evaluate the neuroforamen suffer from poor accuracy, have inherent limitations,
      and fail to provide data throughout the ROM. METHODS: Six cadaveric specimens (L1
      sacrum) were instrumented with radiopaque spheres and CT scanned. 3-Dimensional
      reconstructions were made of each vertebra and the sphere locations determined.
      During kinematic testing, the spheres were located in relation to optoelectronic
      targets attached to each vertebra. The result was a 3-dimensional representation
      of the specimen's CT reconstruction moving in response to experimental data. Bony
      contours of the L2-L3 and L4-L5 neuroforamen were digitized producing continuous
      neuroforaminal area and height data throughout the ROM. RESULTS: Neuroforaminal
      area and height linearly increased in flexion and decreased in extension. There
      was significant correlation between flexion-extension motion and percent change
      in area (L2-L3: 3.1%/deg, R = 0.94, L4-L5: 2.5%/deg, R = 0.90) and neuroforaminal
      height (L2-L3: 2.1%/deg, R = 0.95, L4-L5: 1.6%/deg, R = 0.93). Regression
      analysis showed that the ratio between neuroforaminal height and area is at least
      1:1.5 such that a 100% increase in height is associated with an area increase of
      more than 150%. CONCLUSION: This is the first study to measure lumbar
      neuroforaminal area and height throughout flexion-extension ROM. The CT-based
      specimen-specific model technique can accurately evaluate the effect of
      kinematics on morphological features of the spine. The demonstrated increase in
      neuroforaminal dimension in flexion is consistent with treatment modalities used
      in clinical therapies to relieve radicular symptoms. LEVEL OF EVIDENCE: N/A.

PMID- 25943083
TI  - Which daily functions are most affected by stiffness following total lumbar
      fusion: comparison of upper thoracic and thoracolumbar proximal endpoints.
AB  - STUDY DESIGN: Retrospective review of a multicenter, prospective adult spinal
      deformity (ASD) database. OBJECTIVE: The objective was to evaluate the impact of
      stiffness on activities of daily living (ADL) after instrumented total lumbar
      fusions to the pelvis; specifically between patients with the upper-most
      instrumented vertebra (UIV) within the upper thoracic (UT) versus the
      thoracolumbar (TL) region. SUMMARY OF BACKGROUND DATA: The Lumbar Stiffness
      Disability Index (LSDI) has been validated and used in clinical studies as a self
      reported outcomes tool; however, the impact of stiffness on the 10 specific ADLs
      comprising the LSDI has not been evaluated. METHODS: A retrospective comparison
      of prospectively collected pre- and 2-year minimum postoperative answers to the
      10 questions comprising the LSDI among patients with ASD was conducted. Cohorts
      were defined based on the UIV as UT (T1-T6) or TL (T9-L1). RESULTS: 134 patients
      were included (UT:64, TL:70). Both groups had statistically similar changes in
      all individual LSDI scores at 2 years versus preoperative values (P > 0.05l) with
      the exception of questions #2 (Bend through your waist to put socks and shoes on)
      and #8 (bathe lower half of body) in which UT reported increased difficulty (P <
      0.05). Both groups had statistically similar individual LSDI question scores with
      the exception of 2-year question #4 (hygiene after toileting) in which UT had a
      significantly worse score (P < 0.05). CONCLUSION: Patients with ASD undergoing
      instrumented total lumbar fusions to the ilium report limited changes from
      baseline in the ability to perform the 10 ADL functions of the LSDI and had
      limited differences in final scores regardless of whether the UIV was in the UT
      or TL region. Domains showing the greatest change from baseline involved dressing
      or bathing the lower half of the body among patients with UT. The only domain for
      which UT had greater impairment was in performing personal hygiene functions
      after toileting. LEVEL OF EVIDENCE: 3.

PMID- 25943084
TI  - Clinical pedicle screw accuracy and deviation from planning in robot-guided spine
      surgery: robot-guided pedicle screw accuracy.
AB  - STUDY DESIGN: A retrospective chart review was performed for 112 consecutive
      minimally invasive spinal surgery patients who underwent pedicular screw fixation
      in a community hospital setting. OBJECTIVE: To assess the clinical accuracy and
      deviation in screw positions in robot-assisted pedicle screw placement. SUMMARY
      OF BACKGROUND DATA: Accuracy of pedicle screw placement in in vivo studies varies
      widely, especially when minimally invasive techniques are used. Robotic guidance
      was recently introduced to increase screw placement accuracy but still reported
      accuracies vary. METHODS: Reproducibility of the surgeon's plan using robotic
      guidance was assessed by fusing individual vertebras from the preoperative
      computed tomography (CT) containing the planning with a postoperative CT.
      Deviation in entry point and difference in angle of insertion was measured on
      axial and sagittal planes. Grading of pedicle screw placement was performed on
      postoperative CTs using the Gertzbein-Robbins classification. RESULTS: CT-to-CT
      fusion succeeded for 178 screws, but these appeared to be random, with no
      apparent selection bias. Mean deviation in entry point was 2.0 +/- 1.2 mm. Mean
      difference in angle of insertion was 2.2 degrees  +/- 1.7 degrees  on the axial
      plane and 2.9 degrees  +/- 2.4 degrees  on the sagittal plane. Assessment of
      pedicle screw accuracy showed that 477 of 487 screws (97.9%) were safely placed
      (<2 mm, category A+B), 8 screws in category C and 1 in category D. None of the
      screws necessitated resurgery for revised placement. CONCLUSION: Preoperative
      planning of robotic guidance is reproduced intraoperatively within acceptable
      deviations. We conclude that robotic guidance allows for highly accurate
      execution of the preoperative plan, leading to accurate screw placement. LEVEL OF
      EVIDENCE: 3.

PMID- 25943085
TI  - The Effect of Epidural Steroid Injection on Postoperative Outcome in Patients
      From the Lumbar Spinal Stenosis Outcome Study.
AB  - STUDY DESIGN: Retrospective analysis of data from patients participating in the
      Lumbar Spinal Stenosis Outcome Study (LSOS). OBJECTIVE: The aim of LSOS was to
      assess clinical outcomes after surgical or nonoperative treatment in patients
      with and without prior epidural steroid injections. SUMMARY OF BACKGROUND DATA:
      Epidural steroid injections (ESI), a common treatment modality, reduce symptoms
      in the short-term, but according to a subgroup analysis from the Spine Patient
      Outcomes Research Trial (SPORT) they reduce the amount of improvement after
      subsequent surgical or nonoperative treatment. METHODS: The data of 281 patients
      with lumbar spinal stenosis who had completed baseline and 6-month follow-up
      assessments were analyzed. Patients completed the Spinal Stenosis Measure (SSM).
      Changes in the SSM scores from baseline to follow-up were compared between
      patients with and without prior ESI, for the surgical and nonsurgical treatment
      groups. RESULTS: The mean (SD) age of the patients was 75 (8.7) years. 229
      patients underwent surgery and 111 of these had received an ESI in the 12 months
      before surgery. Of the 52 patients treated nonoperatively, 29 had received a
      prior ESI. The unadjusted changes (improvement) in the SSM-symptom scores between
      baseline and 6 months' follow up were: surgery and prior ESI 0.95, surgery and no
      prior ESI 0.78 (P = 0.15); no surgery and prior ESI 0.28, no surgery and no prior
      ESI 0.29 (P = 0.85). When adjusted for confounding factors, the reduction in SSM
      symptom score was greater for surgery than for nonoperative treatment by 0.41
      points (P < 0.001); the effect of having had an ESI prior to study entry was 
      0.08 (P = 0.40). CONCLUSION: The analysis of outcomes in the LSOS cohort provided
      no evidence that ESIs have a negative effect on the short-term outcome of surgery
      or nonoperative treatment in patients with lumbar spinal stenosis. LEVEL OF
      EVIDENCE: 3.

PMID- 25943087
TI  - Beyond the Jargon: Architecture, Process, and Clinical Care.

PMID- 25943086
TI  - SRS22R Appearance Domain Correlates Most With Patient Satisfaction After Adult
      Deformity Surgery to the Sacrum at 5-year Follow-up.
AB  - STUDY DESIGN: Longitudinal cohort. OBJECTIVE: To evaluate the relationship
      between Scoliosis Research Society-22R (SRS22-R) domains and satisfaction with
      management in patients who underwent surgical correction for adult spine
      deformity. SUMMARY OF BACKGROUND DATA: The SRS-22R is used to measure clinical
      outcomes in adult spine deformity patients. The relationship between patient
      satisfaction and SRS-22R domain scores, the Oswestry Disability Index (ODI) and
      radiographical parameters has not been reported at 5-year follow-up. METHODS: 135
      patients with adult spinal deformity at a single institution who underwent a
      posterior spinal fusion of 5 levels or more to the sacrum and had complete SRS
      22R pre- and minimum 5-year postoperative were identified. Wilcoxon tests were
      used to compare preoperative and 5-year postoperative scores. Spearman
      correlations were used to evaluate associations between the 5-year SRS-22R
      Satisfaction score and changes in SRS-22R domain scores, SubScore (SRS-22R Total
      Satisfaction), ODI, and radiographical parameters. RESULTS: There were 125
      females and 10 males with a mean BMI of 26.6 kg/m and mean age of 53.6 years.
      There were 74 primary and 61 revision surgeries with a mean 9.9 levels fused and
      mean follow-up of 67 months. There was a statistically significant improvement
      between paired pre- and 5-year postop SRS-22R domain scores and most
      radiographical parameters, commonly P <= 0.001. The majority of patients had an
      SRS-22R Satisfaction score of 3.0 or more (88%) or 4.0 or more (67%), consistent
      with a moderate ceiling effect. Correlations for SRS-22R domain scores were all
      statistically significant and either weak [Mental (0.26), Activity (0.27), Pain
      (0.35), or moderate (Appearance (0.59))]. SRS-22R SubScore (0.54) and ODI (0.43)
      also had a moderate correlation. Correlations for all radiographical and
      operative parameters were either very weak or weak. CONCLUSION: SRS-22R
      Appearance, SubScore, and ODI correlate most with patient satisfaction in adult
      deformity patients undergoing 5 or more level fusion to the sacrum at 5-year
      follow-up. LEVEL OF EVIDENCE: 2.

PMID- 25943088
TI  - The Influence of No Fault Compensation on Functional Outcomes After Lumbar Spine
      Fusion.
AB  - STUDY DESIGN: Prospective cohort study and systematic literature review.
      OBJECTIVE: To compare the functional outcomes for lumbar spinal fusion in both
      compensation and noncompensation patients in an environment of universal no fault
      compensation and then to compare these outcomes with those in worker's
      compensation and nonworkers compensation cohorts from other countries. SUMMARY OF
      BACKGROUND DATA: Compensation has an adverse effect on outcomes in spine fusion
      possibly based on adversarial environment, delayed resolution of claims and care,
      and increased compensation associated with prolonged disability. It is unclear
      whether a universal no fault compensation system would provide different outcomes
      for these patients. New Zealand's Accident Compensation Corporation (ACC)
      provides universal no fault compensation for personal injury secondary to
      accident and offers an opportunity to compare results with differing provision of
      compensation. METHODS: A total of 169 patients undergoing lumbar spinal fusion
      were assessed preoperatively, at 1 year, and at long-term follow-up out to 14
      years, using functional outcome measures and health-related quality-of-life
      measures. Comparison was made between those covered and not covered by ACC for 3
      distinct diagnostic categories. A systematic literature review comparing outcomes
      in Worker's Compensation and non-Compensation cohorts was also performed.
      RESULTS: The functional outcomes for both ACC and non-ACC cohorts were similar,
      with significant and comparable improvements over the first year that were then
      sustained out to long-term follow-up for both cohorts. At long-term follow-up,
      the health-related quality-of-life measures were the same between the 2
      cohorts.The literature review revealed a marked difference in outcomes between
      worker's compensation and non-worker's compensation cohorts with a near universal
      inferior outcome for the compensation group. CONCLUSION: The similarities in
      outcomes of patients undergoing lumbar spine fusion under New Zealand's universal
      no fault compensation system, when compared with the dramatically inferior
      outcomes for these patients under other worker's compensation systems, suggest
      that the system of compensation has a major influence on patient outcomes, and
      that change of compensation to a universal no fault system is beneficial for
      patients undergoing lumbar fusion surgery. LEVEL OF EVIDENCE: 2.

PMID- 25943089
TI  - Point of View.

PMID- 25943090
TI  - Multifidus Muscle Changes After Back Injury Are Characterized by Structural
      Remodeling of Muscle, Adipose and Connective Tissue, but Not Muscle Atrophy:
      Molecular and Morphological Evidence.
AB  - STUDY DESIGN: Longitudinal case-controlled animal study. OBJECTIVE: To
      investigate putative cellular mechanisms to explain structural changes in muscle
      and adipose and connective tissues of the back muscles after intervertebral disc
      (IVD) injury. SUMMARY OF BACKGROUND DATA: Structural back muscle changes are
      ubiquitous with back pain/injury and considered relevant for outcome, but their
      exact nature, time course, and cellular mechanisms remain elusive. We used an
      animal model that produces phenotypic back muscle changes after IVD injury to
      study these issues at the cellular/molecular level. METHODS: Multifidus muscle
      was harvested from both sides of the spine at L1-L2 and L3-L4 IVDs in 27
      castrated male sheep at 3 (n = 10) or 6 (n = 17) months after a surgical
      anterolateral IVD injury at both levels. Ten control sheep underwent no surgery
      (3 mo, n = 4; 6 mo, n = 6). Tissue was harvested at L4 for histological analysis
      of cross-sectional area of muscle and adipose and connective tissue (whole
      muscle), plus immunohistochemistry to identify proportion and cross-sectional
      area of individual muscle fiber types in the deepest fascicle. Quantitative
      polymerase chain reaction measured gene expression of typical cytokines/signaling
      molecules at L2. RESULTS: Contrary to predictions, there was no multifidus muscle
      atrophy (whole muscle or individual fiber). There was increased adipose and
      connective tissue (fibrotic proliferation) cross-sectional area and slow-to-fast
      muscle fiber transition at 6 but not 3 months. Within the multifidus muscle,
      increases in the expression of several cytokines (tumor necrosis factor alpha and
      interleukin-1beta) and molecules that signal trophic/atrophic processes for the 3
      tissue types (e.g., growth factor pathway [IGF-1, PI3k, Akt1, mTOR], potent
      tissue modifiers [calcineurin, PCG-1alpha, and myostatin]) were present.
      CONCLUSION: This study provides cellular evidence that refutes the presence of
      multifidus muscle atrophy accompanying IVD degeneration at this intermediate time
      point. Instead, adipose/connective tissue increased in parallel with the
      expression of the genes that provide putative mechanisms for multifidus
      structural remodeling. This provides novel targets for pharmacological and
      physical interventions. LEVEL OF EVIDENCE: N/A.

PMID- 25943091
TI  - Postpartum cervical repair in mice: a morphological characterization and
      potential role for angiogenic factors.
AB  - The cervix undergoes marked mechanical trauma during delivery of the baby at
      birth. As such, a timely and complete tissue repair postpartum is necessary to
      prevent obstetrical complications, such as cervicitis, ectropion, hemorrhage,
      repeated miscarriages or abortions and possibly preterm labor and malignancies.
      However, our knowledge of normal cervical repair is currently incomplete and
      factors that influence repair are unclear. Here, we characterize the
      morphological and angiogenic profile of postpartum repair in mice cervix during
      the first 48 h of postpartum. The key findings presented here are: (1) cervical
      epithelial folds and size are diminished during the first 48 h of postpartum
      repair, (2) hypoxic inducible factor 1a, vascular endothelial growth factor
      (VEGF), and VEGF receptor 1 expression are pronounced early in postpartum
      cervical repair, and (3) VEGF receptor 2 gene and protein expressions are
      variable. We conclude that postpartum cervical repair involves gross and
      microscopic changes and is linked to expression of angiogenic factors. Future
      studies will assess the suitability of these factors, identified in the present
      study, as potential markers for determining the phase of postpartum cervical
      repair in obstetrical complications, such as cervical lacerations. 

PMID- 25943092
TI  - Autophagy may contribute to the recovery of rat mesothelium following acute
      inflammation in vivo.
AB  - Following Freund's adjuvant-induced acute inflammation, the regeneration of rat
      mesothelium is accompanied by the reduction of cell organelles. The aim of the
      present study is to test whether autophagy may play a role in the recovery
      process of mesothelial cells by eliminating accumulated cell organelles and also
      to investigate the presence of potential inducers and molecular transmitters of
      the process. Control and treated (from day 2 to day 11; D2-D11) mesothelial cells
      (n = 16 samples/group) obtained from male rats were isolated and phenotypically
      characterized. Morphological studies included light and electron microscopy.
      Biochemical studies performed on tissue samples as well as isolated cells were
      used to evaluate the dynamics of autophagy and also to detect the expression
      levels of TNF-alpha, LC3B, estrogen receptors (ER-alpha and GPR30) and Erk1/2.
      Gene expression was measured by individual Taqman assays on quantitative RT-PCR.
      Protein expression study was performed by Western blotting and immunolabeling.
      Estradiol concentration was measured both in peritoneal fluid and plasma samples
      in control and treated animals (n = 3-10 animals per group). Our conventional
      electron microscopic and morphometric results showed a progressive autophagosome
      formation with a peak by the termination of inflammation (D5). Subsequently,
      autophagolysosome formation dominated between D6 and D8 with a concomitant
      expression of LC3B proved by immunoblotting. We further observed the reduction of
      cell compartments by D11 parallel with the morphological restitution of
      mesothelium. Estradiol showed a sustained level in the peritoneal fluid but not
      in plasma samples between D3 and D11 compared to levels obtained from untreated
      animals. The mRNA expression of TNF-alpha was increased between D2 and D11
      compared to control. Western blot analysis showed a constitutive expression of
      GPR30, while ER-alpha could not be detected between D6 and D11. Erk1/2 was
      activated by phosphorylation with a peak at D6. Considering our present in vivo
      results, we hypothesize that the facilitated autophagy might play an important
      role in the removal of cytoplasmic organelles during the recovery of mesothelium,
      while our results also suggest that the detected peritoneal estradiol as well as
      TNF-alpha may contribute to this process. 

PMID- 25943093
TI  - Subcutaneous Stimulation as an Additional Therapy to Spinal Cord Stimulation for
      the Treatment of Low Back Pain and Leg Pain in Failed Back Surgery Syndrome: Four
      Year Follow-Up.
AB  - OBJECTIVE: The objective of this study is to investigate the efficacy of long
      term follow-up of subcutaneous stimulation (SubQ) as an additional therapy for
      patients with failed back surgery syndrome (FBSS) with chronic refractory pain,
      for whom spinal cord stimulation (SCS) alone was unsuccessful in treating low
      back pain. STUDY DESIGN: Prospective case series. MATERIALS AND METHODS: FBSS
      patients with leg and/or low back pain whose conventional therapies had failed,
      received a combination of SCS (8-contact Octad lead, 3877-45 cm, Medtronic,
      Minneapolis, MN, USA) and/or SubQ (4-contact Quad Plus lead (s), 2888-28 cm,
      Medtronic). Initially, an Octad lead was placed in the epidural space for SCS for
      a trial stimulation to assess the suppression of leg and/or low back pain. Where
      SCS alone was insufficient in treating low back pain, lead(s) were placed
      superficially in the subcutaneous tissue of the lower back, exactly in the middle
      of the pain area. A pulse generator (Prime Advanced, 37702, Medtronic) was
      implanted if the patient reported more than 50% pain relief during the trial
      period. We investigated the long-term effect of neuromodulation on pain with the
      visual analog scale (VAS), and disability using the Quebec Pain Disability Scale.
      The results after 46 months are presented. RESULTS: Eleven patients, five men and
      six women (age 51 +/- 8 years, mean +/- SD) were included in the pilot study. In
      nine cases, SCS was used in combination with SubQ leads. Two patients received
      only SubQ leads. In one patient, the SCS + SubQ system was removed after nine
      months and these results were not taken into account for the analysis. Baseline
      scores for leg (N = 8) and low back pain (N = 10) were VASbl: 59 +/- 15 and
      VASbl: 63 +/- 14, respectively. The long-term follow-up period was 46 +/- 4
      months. SCS significantly reduced leg pain after 12 months (VAS12: 20 +/- 11, p12
      = 0.001) and 46 months (VAS46: 37 +/- 17, p46 = 0.027). Similarly, SubQ
      significantly reduced back pain after 12 months(VAS12: 33 +/- 16, p12 = 0.001)
      and 46 months (VAS46: 40 +/- 21, p46 = 0.013). At 12 months, the Quebec Pain
      Disability Scale (QPDS) was 49 +/- 12 and after 46 months, 53 +/- 15. Both at 12
      and 46 months, the QPDS values were statistically significantly better (p12 =
      0.001, p46 = 0.04) compared with baseline values (QPDSbl: 61 +/- 15). In one
      patient, the pain suppressive effect of SCS/SubQ had disappeared completely over
      time and the pain scores returned to prestimulation values. In four, patients
      back pain scores increased over time due to new issues (SI-joint problems,
      degenerative spine problems, disc problems, and hip pain) unrelated to FBSS and
      for which SCS/SubQ was not targeted or a reason for implantation at the start of
      the pilot study. DISCUSSION: This is the first prospective report on the combined
      use of SCS and SubQ with a follow-up period of four years. These data show that
      SCS and/or SubQ provide persistent long-term pain relief for leg and back pain in
      patients with FBSS. One should also take into account that new back/leg pain
      problems may evolve over time and increase the pain score which impact overall
      pain treatment. CONCLUSION: SCS combined with SubQ can be considered an effective
      long term treatment for low back pain in patients with FBSS for whom SCS alone is
      insufficient in alleviating their pain symptoms.

PMID- 25943094
TI  - Injectable Hyaluronan Hydrogels with Peptide-Binding Dendrimers Modulate the
      Controlled Release of BMP-2 and TGF-beta1.
AB  - BMP-2 and TGF-beta1 released from injectable thermoresponsive hydrogels are
      studied in the presence and absence of branched macromolecules bearing BMP-2 or
      TGF-beta1 affinity binding peptides. The synthesized branched macromolecules and
      the gelling compositions before and after loading with either BMP-2 or TGF-beta1
      are characterized physico-chemically and show a significantly lower amount of
      proteins released in the presence of the affinity binding peptide macromolecules.
      This study illustrates the potential of affinity binding peptide functionalized
      dendrimers to modulate the local delivery and availability of growth factors
      important for musculoskeletal regeneration therapies. 

PMID- 25943095
TI  - CRISPR-Cas targeted plasmid integration into mammalian cells via non-homologous
      end joining.
AB  - Mammalian cells are widely used for the production of therapeutic recombinant
      proteins, as these cells facilitate accurate folding and post-translational
      modifications often essential for optimum activity. Targeted insertion of a
      plasmid harboring a gene of interest into the genome of mammalian cells for the
      expression of a desired protein is a key step in production of such biologics.
      Here we show that a site specific double strand break (DSB) generated both in the
      genome and the donor plasmid using the CRISPR-Cas9 system can be efficiently used
      to target ~5 kb plasmids into mammalian genomes via nonhomologous end joining
      (NHEJ). We were able to achieve efficiencies of up to 0.17% in HEK293 cells and
      0.45% in CHO cells. This technique holds promise for quick and efficient
      insertion of a large foreign DNA sequence into a predetermined genomic site in
      mammalian cells.

PMID- 25943096
TI  - Complete transection of the urethra and corpora cavernosa: a complication after
      laparoscopic repair (TEP) of an inguinal hernia.
AB  - Complete transection of both corpora cavernosa and the urethra is a very rare
      condition in urology. We report the case of a 59-year-old man with complete
      transection of the corpora cavernosa and the urethra during a laparoscopic repair
      of a recurrent inguinal hernia.

PMID- 25943097
TI  - Multi-innovation auto-constructed least squares identification for 4 DOF ship
      manoeuvring modelling with full-scale trial data.
AB  - This research is concerned with the problem of 4 degrees of freedom (DOF) ship
      manoeuvring identification modelling with the full-scale trial data. To avoid the
      multi-innovation matrix inversion in the conventional multi-innovation least
      squares (MILS) algorithm, a new transformed multi-innovation least squares
      (TMILS) algorithm is first developed by virtue of the coupling identification
      concept. And much effort is made to guarantee the uniformly ultimate convergence.
      Furthermore, the auto-constructed TMILS scheme is derived for the ship
      manoeuvring motion identification by combination with a statistic index.
      Comparing with the existing results, the proposed scheme has the significant
      computational advantage and is able to estimate the model structure. The
      illustrative examples demonstrate the effectiveness of the proposed algorithm,
      especially including the identification application with full-scale trial data. 

PMID- 25943098
TI  - Key challenges in the treatment of rare pediatric skeletal genetic disorders:
      from bench to bedside.

PMID- 25943099
TI  - Hyperinflation deteriorates arterial oxygenation and lung injury in a rabbit
      model of ARDS with repeated open endotracheal suctioning.
AB  - BACKGROUND: Hyperinflation (HI) is performed following open endotracheal
      suctioning (OES), whose goals include: to stimulate a cough, recover oxygenation
      and improve compliance. However, it may also induce unintended consequences,
      including: lung stress and strain, failure to maintain high distending pressure,
      and subsequently cycling recruitment and derecruitment. Here, our aim was to
      investigate the effects of hyperinflation after repeated OES on sequential
      alteration of arterial oxygenation and lung injury profile using a saline lavage
      induced surfactant depleted ARDS rabbit model. METHODS: Briefly, 30 Japanese
      White Rabbits were anesthetized and ventilated in pressure-controlled setting
      with a tidal volume of 6-8 ml/kg. Animals were divided into four groups, i.e.;
      Control, ARDS, OES, and HI. Saline-lavage-induced lung injury was induced except
      for Control group. Thereafter, rabbits were ventilated with positive-end
      expiratory pressure (PEEP) at 10 cm H2O. The ARDS group received ventilation with
      the same PEEP without derecruitment. As intervention, OES and HI were performed
      in ARDS animals. OES was performed for 15 seconds at 150 mm Hg, whereas HI was
      performed with PEEP at 0 cm H2O and peak inspiratory pressure at +5 cm H2O for a
      minute. Total duration of the experiment was for 3 hours. OES and HI were
      performed every 15 minutes from beginning of the protocol. RESULTS: PaO2 was
      maintained at about 400 mm Hg in both control and ARDS groups for the duration of
      this study, while in both OES and HI groups, PaO2 decreased continuously up to 3
      hours, dropped to a mean (+/-SD) of 226 +/- 28.9 and 97.0 +/- 30.7 mmHg at 3 h,
      respectively. HI group had the lowest PaO2 in the present investigation.
      Histological lung injury score was the highest in HI group than other three
      groups. Pulmonary TNF-alpha and IL-8 levels were the highest in HI group compared
      to other groups, but without significant alterations at circulatory level in all
      the experimental groups. CONCLUSIONS: We show in the present study that
      hyperinflation following repeated OES deteriorate arterial oxygenation and the
      severity of lung injury in a rabbit model of ARDS undergoing mechanical
      ventilation.

PMID- 25943100
TI  - DNA methylation differences in monozygotic twin pairs discordant for
      schizophrenia identifies psychosis related genes and networks.
AB  - BACKGROUND: Despite their singular origin, monozygotic twin pairs often display
      discordance for complex disorders including schizophrenia. It is a common (1%)
      and often familial disease with a discordance rate of ~50% in monozygotic twins.
      This high discordance is often explained by the role of yet unknown
      environmental, random, and epigenetic factors. The involvement of DNA methylation
      in this disease appears logical, but remains to be established. METHODS: We have
      used blood DNA from two pairs of monozygotic twins discordant for schizophrenia
      and their parents in order to assess genome-wide methylation using a NimbleGen
      Methylation Promoter Microarray. RESULTS: The genome-wide results show that
      differentially methylated regions (DMRs) exist between members representing
      discordant monozygotic twins. Some DMRs are shared with parent(s) and others
      appear to be de novo. We found twenty-seven genes affected by DMR changes that
      were shared in the affected member of two discordant monozygotic pairs from
      unrelated families. Interestingly, the genes affected by pair specific DMRs share
      specific networks. Specifically, this study has identified two networks; "cell
      death and survival" and a "cellular movement and immune cell trafficking". These
      two networks and the genes affected have been previously implicated in the
      aetiology of schizophrenia. CONCLUSIONS: The results are compatible with the
      suggestion that DNA methylation may contribute to the discordance of monozygotic
      twins for schizophrenia. Also, this may be accomplished by the direct effect of
      gene specific methylation changes on specific biological networks rather than
      individual genes. It supports the extensive genetic, epigenetic and phenotypic
      heterogeneity implicated in schizophrenia.

PMID- 25943101
TI  - HBx induced AFP receptor expressed to activate PI3K/AKT signal to promote
      expression of Src in liver cells and hepatoma cells.
AB  - BACKGROUND: Hepatitis B virus (HBV)-X protein(HBx) is a transactivator of host
      several cellular genes including alpha-fetoprotein(AFP) and AFP receptor(AFPR)
      which contributes to HBV-associated tumor development. The expression of AFP/AFPR
      are correlated with hepatocellular carcinoma(HCC)-initial cells. But the role of
      AFP and AFPR in promoting occurrence of HBV-related HCC were still unclear.
      METHODS: A total of 71 clinical patients' liver specimens, normal human liver
      cells L-02 and HCC cell lines, PLC/PRF/5 were selected for analyzing the effects
      of HBx on expression of AFP, AFPR and Src. The expression of goal proteins were
      detected by Immunohistochemical stained and Western blotting; HBx-expressed
      vectors were constructed and transfected into L-02 cells, laser confocal
      microscopy was applied to observe expression and location of AFP, AFPR and Src in
      the normal liver cells and HCC cells, soft agar colony formation assay was used
      to observe colonies formed of the cells. RESULTS: We confirmed HBx gives
      preference to promote the expression of AFP and AFPR; HBx priors to up-regulate
      the expression of AFPR and AFP in L-02 cells and in normal liver specimens; AFPR
      signal been able to stimulate Src expression. The results also indicated that
      phosphatidylinositol 3-kinase(PI3K) inhibitors Ly294002 and GDC0941 effectively
      suppress AFPR mediated up-regulation expression of Src in AFPR positive HCC
      lines. CONCLUSIONS: HBx priors to drive the expression of AFP and AFPR to promote
      expression of Src in normal liver cells and hepatoma cells; AFP and AFPR maybe
      play pivotal role in HBV-related hepatocarcinogenesis; Targeting AFPR is an
      available therapeutic strategy of HCC.

PMID- 25943102
TI  - Development of oral health policy in Nigeria: an analysis of the role of context,
      actors and policy process.
AB  - BACKGROUND: In Nigeria, there is a high burden of oral health diseases, poor
      coordination of health services and human resources for delivery of oral health
      services. Previous attempts to develop an Oral Health Policy (OHP) to decrease
      the oral disease burden failed. However, a policy was eventually developed in
      November 2012. This paper explores the role of contextual factors, actors and the
      policy process in the development of the OHP and possible reasons why the current
      approved OHP succeeded. METHODS: The study was undertaken across Nigeria;
      information gathered through document reviews and in-depth interviews with five
      groups of purposively selected respondents. Analysis of the policy development
      process was guided by the policy triangle framework, examining context, policy
      process and actors involved in the policy development. RESULTS: The foremost
      enabling factor was the yearning among policy actors for a policy, having had
      four failed attempts. Other factors were the presence of a democratically elected
      government, a framework for health sector reform instituted by the Federal
      Ministry of Health (FMOH). The approved OHP went through all stages required for
      policy development unlike the previous attempts. Three groups of actors played
      crucial roles in the process, namely academics/researchers, development partners
      and policy makers. They either had decision making powers or influenced policy
      through funding or technical ability to generate credible research evidence, all
      sharing a common interest in developing the OHP. Although evidence was used to
      inform the development of the policy, the complex interactions between the
      context and actors facilitated its approval. CONCLUSIONS: The OHP development
      succeeded through a complex inter-relationship of context, process and actors,
      clearly illustrating that none of these factors could have, in isolation,
      catalyzed the policy development. Availability of evidence is necessary but not
      sufficient for developing policies in this area. Wider socio-political contexts
      in which actors develop policy can facilitate and/or constrain actors' roles and
      interests as well as policy process. These must be taken into consideration at
      stages of policy development in order to produce policies that will strengthen
      the health system, especially in low and middle-income countries, where policy
      processes and influences can be often less than transparent.

PMID- 25943103
TI  - A systematic review of hepatic tuberculosis with considerations in human
      immunodeficiency virus co-infection.
AB  - BACKGROUND: Mycobacterium tuberculosis (TB) infection of the liver, known as
      hepatic TB, is an extrapulmonary manifestation of TB. Hepatic TB has become more
      prevalent, likely as a result of the human immunodeficiency virus/acquired
      immunodeficiency syndrome (HIV/AIDS) epidemic. We sought to review case series to
      characterize the epidemiology, pathophysiology, clinical features, diagnosis, and
      treatment of hepatic TB and to comment on the impact of HIV co-infection on these
      characteristics. METHODS: We conducted a systematic literature search in PubMed
      and ScienceDirect for articles pertaining to hepatic TB with human subjects from
      1960 to July 2013. RESULTS: We obtained data on 618 hepatic TB patients from 14
      case series. The most common reported signs and symptoms were hepatomegaly
      (median: 80%, range: 10-100%), fever (median: 67%, range: 30-100), respiratory
      symptoms (median: 66%, range: 32-78%), abdominal pain (median: 59.5%, range: 40
      83%), and weight loss (median: 57.5%, range: 20-100%). Common laboratory
      abnormalities were elevated alkaline phosphatase and gamma-glutamyl transferase.
      Ultrasound and computerized tomography (CT) were sensitive but non-specific. On
      liver biopsy, smear microscopy for acid-fast bacilli had a median sensitivity of
      25% (range: 0-59%), histology of caseating granulomas had a median sensitivity of
      68% (range: 14-100%), and polymerase chain reaction for TB had a median
      sensitivity of 86% (range: 30-100%). Standard anti-tuberculous chemotherapy for 6
      to 12 months achieved positive outcomes for nearly all patients with drug
      susceptible TB. CONCLUSIONS: Clinicians in TB-endemic regions should maintain a
      high index of suspicion for hepatic TB in patients presenting with hepatomegaly,
      fever, respiratory symptoms, and elevated liver enzymes. The most sensitive
      imaging modality is a CT scan, while the most specific diagnostic modality is a
      liver biopsy with nucleic acid testing of liver tissue samples. Upon diagnosis, 4
      drug anti-TB therapy should promptly be initiated. HIV co-infected patients may
      have more complex cases and should be closely monitored for complications.

PMID- 25943104
TI  - Activation of defence pathways in Scots pine bark after feeding by pine weevil
      (Hylobius abietis).
AB  - BACKGROUND: During their lifetime, conifer trees are exposed to numerous
      herbivorous insects. To protect themselves against pests, trees have developed a
      broad repertoire of protective mechanisms. Many of the plant's defence reactions
      are activated upon an insect attack, and the underlying regulatory mechanisms are
      not entirely understood yet, in particular in conifer trees. Here, we present the
      results of our studies on the transcriptional response and the volatile compounds
      production of Scots pine (Pinus sylvestris) upon the large pine weevil (Hylobius
      abietis) feeding. RESULTS: Transcriptional response of Scots pine to the weevil
      attack was investigated using a novel customised 36.4 K Pinus taeda microarray.
      The weevil feeding caused large-scale changes in the pine transcriptome. In
      total, 774 genes were significantly up-regulated more than 4-fold (p<=0.05),
      whereas 64 genes were significantly down-regulated more than 4-fold. Among the up
      regulated genes, we could identify genes involved in signal perception,
      signalling pathways, transcriptional regulation, plant hormone homeostasis,
      secondary metabolism and defence responses. The weevil feeding on stem bark of
      pine significantly increased the total emission of volatile organic compounds
      from the undamaged stem bark area. The emission levels of monoterpenes and
      sesquiterpenes were also increased. Interestingly, we could not observe any
      correlation between the increased production of the terpenoid compounds and
      expression levels of the terpene synthase-encoding genes. CONCLUSIONS: The
      obtained data provide an important insight into the transcriptional response of
      conifer trees to insect herbivory and illustrate the massive changes in the host
      transcriptome upon insect attacks. Moreover, many of the induced pathways are
      common between conifers and angiosperms. The presented results are the first ones
      obtained by the use of a microarray platform with an extended coverage of pine
      transcriptome (36.4 K cDNA elements). The platform will further facilitate the
      identification of resistance markers with the direct relevance for conifer tree
      breeding.

PMID- 25943105
TI  - Optimization of genomic selection training populations with a genetic algorithm.
AB  - In this article, we imagine a breeding scenario with a population of individuals
      that have been genotyped but not phenotyped. We derived a computationally
      efficient statistic that uses this genetic information to measure the reliability
      of genomic estimated breeding values (GEBV) for a given set of individuals (test
      set) based on a training set of individuals. We used this reliability measure
      with a genetic algorithm scheme to find an optimized training set from a larger
      set of candidate individuals. This subset was phenotyped to create the training
      set that was used in a genomic selection model to estimate GEBV in the test set.
      Our results show that, compared to a random sample of the same size, the use of a
      set of individuals selected by our method improved accuracies. We implemented the
      proposed training selection methodology on four sets of data on Arabidopsis,
      wheat, rice and maize. This dynamic model building process that takes genotypes
      of the individuals in the test sample into account while selecting the training
      individuals improves the performance of genomic selection models. 

PMID- 25943106
TI  - Carbon Ion irradiation in the treatment of grossly incomplete or unresectable
      malignant peripheral nerve sheaths tumors: acute toxicity and preliminary
      outcome.
AB  - BACKGROUND: To report our early experience with carbon ion irradiation in the
      treatment of gross residual or unresectable malignant peripheral nerve sheath
      tumors (MPNST). METHODS: We retrospectively analysed 11 patients (pts) with
      MPNST, who have been treated with carbon ion irradiation (C12) at our institution
      between 2010 and 2013. All pts had measurable gross disease at the initiation of
      radiation treatment. Median age was 47 years (29-79). Tumors were mainly located
      in the pelvic/sacral (5 pts) and sinunasal/orbital region (5 pts). 5 pts
      presented already in recurrent situation, 3 pts had been previously irradiated,
      and in 3 pts MPNST were neurofibromatosis type 1 (NF1) associated. Median
      cumulative dose was 60 GyE. Treatment was carried out either as a combination of
      IMRT plus C12 boost (4 pts) or C12 only (7 pts). RESULTS: Median follow-up was 17
      months (3-31 months). We observed 3 local progressions, translating into
      estimated 1- and 2-year local control rates of 65%. One patient developed distant
      failure, resulting in estimated 1- and 2-year PFS rates of 56%. Two patients have
      died, therefore the estimated 1- and 2-year OS rates are 75%. Acute radiation
      related toxicities were generally mild, no grade 3 side effects were observed.
      Severe late toxicity (grade 3) was scored in 2 patients (trismus, wound healing
      delays). CONCLUSION: Carbon ion irradiation yields very promising short term
      local control and overall survival rates with low morbidity in patients suffering
      from gross residual or unresectable malignant peripheral nerve sheath tumors and
      should be further investigated in a prospective trial.

PMID- 25943108
TI  - Acute abdominal pain in a man with Cushing syndrome.
AB  - Arterial thrombosis or emboli have rarely been reported in Cushing syndrome (CS).
      Here we describe the first case of mesenteric ischaemia secondary to ventricular
      emboli in a patient with CS. Laboratory evaluation showed increased fibrinogen
      and factor VIII. Previous studies showed that venous thromboembolism (VTE)
      increases in CS. This case for the first time described arterial system
      thrombosis and emboli in a patient with adrenocorticotropin (ACTH)-dependent CS. 

PMID- 25943107
TI  - Oxygen and glucose deprivation induces widespread alterations in mRNA translation
      within 20 minutes.
AB  - BACKGROUND: Oxygen and glucose metabolism play pivotal roles in many
      (patho)physiological conditions. In particular, oxygen and glucose deprivation
      (OGD) during ischemia and stroke results in extensive tissue injury and cell
      death. RESULTS: Using time-resolved ribosome profiling, we assess gene expression
      levels in a neural cell line, PC12, during the first hour of OGD. The most
      substantial alterations are seen to occur within the first 20 minutes of OGD.
      While transcription of only 100 genes is significantly altered during one hour of
      OGD, the translation response affects approximately 3,000 genes. This response
      involves reprogramming of initiation and elongation rates, as well as the
      stringency of start codon recognition. Genes involved in oxidative
      phosphorylation are most affected. Detailed analysis of ribosome profiles reveals
      salient alterations of ribosome densities on individual mRNAs. The mRNA-specific
      alterations include increased translation of upstream open reading frames, site
      specific ribosome pauses, and production of alternative protein isoforms with
      amino-terminal extensions. Detailed analysis of ribosomal profiles also reveals
      six mRNAs with translated ORFs occurring downstream of annotated coding regions
      and two examples of dual coding mRNAs, where two protein products are translated
      from the same long segment of mRNA, but in two different frames. CONCLUSIONS:
      These findings uncover novel regulatory mechanisms of translational response to
      OGD in mammalian cells that are different from the classical pathways such as
      hypoxia inducible factor (HIF) signaling, while also revealing sophisticated
      organization of protein coding information in certain genes.

PMID- 25943110
TI  - Spontaneous closure of stoma.
AB  - Intestinal loop stoma is a common surgical procedure performed for various benign
      and malignant abdominal problems, but it rarely undergoes spontaneous closure,
      without surgical intervention. Two male patients presented to our emergency
      surgical department with acute abdominal pain. One of them was diagnosed as
      having rectosigmoid perforation and underwent diversion sigmoid loop colostomy
      after primary closure of the perforation. The other was a known case of carcinoma
      of the rectum who had already undergone low anterior resection with covering loop
      ileostomy; the patient underwent second loop ileostomy, this time for complicated
      intestinal obstruction. To our surprise, both the loop colostomy and ileostomy
      closed spontaneously at 8 weeks and 6 weeks, respectively, without any
      consequences. Spontaneous stoma closure is a rare and interesting event. The
      exact etiology for spontaneous closure remains unknown, but it may be
      hypothesized to result from slow retraction of the stoma, added to the concept of
      a tendency towards spontaneous closure of enterocutaneous fistula.

PMID- 25943109
TI  - Effect of lipopolysaccharide on glucocorticoid receptor function in control nasal
      mucosa fibroblasts and in fibroblasts from patients with chronic rhinosinusitis
      with nasal polyps and asthma.
AB  - BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic
      inflammatory disease of the upper airways frequently associated with asthma.
      Bacterial infection is a feature of CRSwNP that can aggravate the disease and the
      response to glucocorticoid treatment. OBJECTIVE: We examined whether the
      bacterial product lipopolysaccharide (LPS) reduces glucocorticoid receptor (GR)
      function in control nasal mucosa (NM) fibroblasts and in nasal polyp (NP)
      fibroblasts from patients with CRSwNP and asthma. METHODS: NP (n = 12) and NM
      fibroblasts (n = 10) were in vitro pre-incubated with LPS (24 hours) prior to the
      addition of dexamethasone. Cytokine/chemokine secretion was measured by ELISA and
      Cytometric Bead Array. GRalpha, GRbeta, mitogen-activated protein-kinase
      phosphatase-1 (MKP-1) and glucocorticoid-induced leucine zipper (GILZ) expression
      was measured by RT-PCR and immunoblotting, GRalpha nuclear translocation by
      immunocytochemistry, and GRbeta localization by immunoblotting. The role of MKP-1
      and GILZ on dexamethasone-mediated cytokine inhibition was analyzed by small
      interfering RNA silencing. RESULTS: Pre-incubation of nasal fibroblasts with LPS
      enhanced the secretion of IL-6, CXCL8, RANTES, and GM-CSF induced by FBS. FBS
      induced CXCL8 secretion was higher in NP than in NM fibroblasts. LPS effects on
      IL-6 and CXCL8 were mediated via activation of p38alpha/beta MAPK and IKK/NF
      kappaB pathways. Additionally, LPS pre-incubation: 1) reduced dexamethasone's
      capacity to inhibit FBS-induced IL-6, CXCL8 and RANTES, 2) reduced dexamethasone
      induced GRalpha nuclear translocation (only in NM fibroblasts), 3) did not alter
      GRalpha/GRbeta expression, 4) decreased GILZ expression, and 5) did not affect
      dexamethasone's capacity to induce MKP-1 and GILZ expression. MKP-1 knockdown
      reduced dexamethasone's capacity to suppress FBS-induced CXCL8 release.
      CONCLUSION: The bacterial product LPS negatively affects GR function in control
      NM and NP fibroblasts by interfering with the capacity of the activated receptor
      to inhibit the production of pro-inflammatory mediators. This study contributes
      to the understanding of how bacterial infection of the upper airways may limit
      the efficacy of glucocorticoid treatment.

PMID- 25943111
TI  - Medical Journal of Australia editor sacked over opposition to Elsevier
      outsourcing.

PMID- 25943112
TI  - Does Early Versus Delayed Active Range of Motion Affect Rotator Cuff Healing
      After Surgical Repair? A Systematic Review and Meta-analysis.
AB  - BACKGROUND: The timing of passive range of motion (ROM) after surgical repair of
      the rotator cuff (RC) has been shown to affect healing. However, it is unknown if
      early or delayed active ROM affects healing. PURPOSE: To determine whether early
      versus delayed active ROM affects structural results of RC repair surgery. STUDY
      DESIGN: Systematic review and meta-analysis. METHODS: A systematic review of
      articles published between January 2004 and April 2014 was conducted. Structural
      results were compared for early (<6 weeks after surgery) versus delayed (>=6
      weeks after surgery) active ROM using chi-square and Fisher exact tests, as well
      as relative risks (RRs) and 95% CIs. The analyses were stratified by tear size
      and repair method. RESULTS: A total of 37 studies (2251 repairs) were included in
      the analysis, with 10 (649 repairs) in the early group and 27 (1602 repairs) in
      the delayed group. For tears <=3 cm, the risk of a structural tendon defect was
      higher in the early versus delayed group for transosseous plus single-row suture
      anchor repairs (39.7% vs 24.3%; RR, 1.63 [95% CI, 1.28-2.08]). For tears >3 cm,
      the risk of a structural tendon defect was higher in the early versus delayed
      group for suture bridge repairs (48% vs 17.5%; RR, 2.74 [95% CI, 1.59-4.73]) and
      all repair methods combined (40.5% vs 26.7%; RR, 1.52 [95% CI, 1.17-1.97]). For
      tears >5 cm, the risk of structural tendon defect was higher in the early versus
      delayed group for suture bridge repairs (100% vs 16.7%; RR, 6.00 [95% CI, 1.69
      21.26]). There were no statistically significant associations for tears measuring
      <=1, 1-3, or 3-5 cm. CONCLUSION: Early active ROM was associated with increased
      risk of a structural defect for small and large RC tears, and thus might not be
      advisable after RC repair.

PMID- 25943113
TI  - Next-generation microfluidic point-of-care diagnostics.

PMID- 25943114
TI  - Phosphatidylethanols in breath: a possible noninvasive screening test for heavy
      alcohol consumption.

PMID- 25943115
TI  - The First 50 Years of Molecular Pharmacology.
AB  - In this Perspective, former and current editors of Molecular Pharmacology,
      together with the guest editors for this 50th Anniversary Issue, provide a
      historical overview of the journal since its founding in 1965. The substantial
      impact that Molecular Pharmacology has had on the field of pharmacology as well
      as on biomedical science is discussed, as is the broad scope of the journal. The
      authors conclude that, true to the original goals for the journal, Molecular
      Pharmacology today remains an outstanding venue for work that provides a
      mechanistic understanding of drugs, molecular probes, and their biologic targets.

PMID- 25943116
TI  - Estrogen-Induced Cholestasis Leads to Repressed CYP2D6 Expression in CYP2D6
      Humanized Mice.
AB  - Cholestasis activates bile acid receptor farnesoid X receptor (FXR) and
      subsequently enhances hepatic expression of small heterodimer partner (SHP). We
      previously demonstrated that SHP represses the transactivation of cytochrome P450
      2D6 (CYP2D6) promoter by hepatocyte nuclear factor (HNF) 4alpha. In this study,
      we investigated the effects of estrogen-induced cholestasis on CYP2D6 expression.
      Estrogen-induced cholestasis occurs in subjects receiving estrogen for
      contraception or hormone replacement, or in susceptible women during pregnancy.
      In CYP2D6-humanized transgenic (Tg-CYP2D6) mice, cholestasis triggered by
      administration of 17alpha-ethinylestradiol (EE2) at a high dose led to 2- to 3
      fold decreases in CYP2D6 expression. This was accompanied by increased hepatic
      SHP expression and subsequent decreases in the recruitment of HNF4alpha to CYP2D6
      promoter. Interestingly, estrogen-induced cholestasis also led to increased
      recruitment of estrogen receptor (ER) alpha, but not that of FXR, to Shp
      promoter, suggesting a predominant role of ERalpha in transcriptional regulation
      of SHP in estrogen-induced cholestasis. EE2 at a low dose (that does not cause
      cholestasis) also increased SHP (by ~ 50%) and decreased CYP2D6 expression (by
      1.5-fold) in Tg-CYP2D6 mice, the magnitude of differences being much smaller than
      that shown in EE2-induced cholestasis. Taken together, our data indicate that EE2
      induced cholestasis increases SHP and represses CYP2D6 expression in Tg-CYP2D6
      mice in part through ERalpha transactivation of Shp promoter.

PMID- 25943117
TI  - The ClC-7 Chloride Channel Is Downregulated by Hypoosmotic Stress in Human
      Chondrocytes.
AB  - Articular chondrocytes in osteoarthritis (OA) patients are exposed to hypoosmotic
      stress because the osmolality of this synovial fluid is significantly decreased.
      Hypoosmotic stress can cause an efflux of Cl(-) and an associated decrease of
      cell volume. We have previously reported that a Cl(-) conductance contributes to
      the regulation of resting membrane potential and thus can alter intracellular
      Ca(2+) concentration ([Ca(2+)]i) in human chondrocytes. The molecular identity
      and pathologic function of these Cl(-) channels, however, remained to be
      determined. Here, we show that the ClC-7 Cl(-) channel is strongly expressed in a
      human chondrocyte cell line (OUMS-27) and that it is responsible for Cl(-)
      currents that are activated by extracellular acidification (pH 5.0). These acid
      sensitive currents are inhibited by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic
      acid (DIDS; IC50 = 13 MUM) and are markedly reduced by small-interfering RNA
      induced knockdown of ClC-7. DIDS hyperpolarized these chondrocytes, and this was
      followed by an increase in [Ca(2+)]i. ClC-7 knockdown caused a similar
      hyperpolarization of the membrane potential. Short-term culture (48 hours) in
      hypoosmotic medium (270 mOsm) reduced the expression of ClC-7 and decreased the
      acid-sensitive currents. Interestingly, these hypoosmotic culture conditions, or
      ClC-7 knockdown, resulted in enhanced cell death. Taken together, our results
      show that the significant hyperpolarization due to ClC-7 impairment in
      chondrocytes can significantly increase [Ca(2+)]i and cell death. Thus,
      downregulation of ClC-7 channels during the hypoosmotic stress that accompanies
      OA progression is one important concept of the complex etiology of OA. These
      findings suggest novel targets for therapeutic intervention(s) and drug
      development for OA. 

PMID- 25943118
TI  - Evaluation of the piezoelectric properties and voltage generation of flexible
      zinc oxide thin films.
AB  - Local piezoresponse and piezoelectric output voltage were evaluated on ZnO thin
      films deposited by radio-frequency magnetron sputtering on hard Si/Ti/Au and
      flexible Cu-coated polyimide substrates. Three different thicknesses of ZnO films
      were studied (285 nm, 710 nm, and 1380 nm), focusing on characteristics like
      crystallinity, grain size, surface roughness, and morphology. Independent of the
      nature of the metal layer and the substrate, our results show that thicker films
      presented a higher level of crystallinity and a preferential orientation along
      the c-axis direction, as well as a lower density of grain boundaries and larger
      crystal sizes. The improvement of the crystalline structure of the material
      directly enhances its piezoelectric properties, as confirmed by the local
      characterizations performed by piezoresponse force microscopy and by the
      evaluation of the output voltage generation under the application of a periodical
      mechanical deformation on the whole film. In particular, the highest value of the
      d33 coefficient obtained (8 pm V(-1)) and the highest generated output voltage
      (0.746 V) belong to the thickest films on hard and flexible substrates,
      respectively. These results envision the use of ZnO thin films--particularly on
      flexible substrates--as conformable, reliable, and efficient active materials for
      use in nanosensing, actuation, and piezoelectric nanogenerators.

PMID- 25943119
TI  - Bovine non-competent oocytes (BCB-) negatively impact the capacity of competent
      (BCB+) oocytes to undergo in vitro maturation, fertilisation and embryonic
      development.
AB  - Competent oocyte selection remains a bottleneck in the in vitro production (IVP)
      of mammalian embryos. Among the vital assays described for selecting competent
      oocytes for IVP, the brilliant cresyl blue (BCB) test has shown consistent
      results. The aim of the first experiment was to observe if oocytes directly
      submitted to IVM show similar cleavage and blastocyst rates as those obtained
      with oocytes maintained under the same in vitro conditions as the oocytes that
      undergo the BCB test. Bovine cumulus-oocyte complexes (COCs) were recovered from
      slaughterhouse-derived ovaries and, after morphological evaluation, were
      randomised grouped into three groups: (1) directly submitted to IVM; (2) oocytes
      submitted to the BCB test without the addition of BCB stain (BCB control group);
      and (3) submitted to the BCB test. The results showed that oocytes directly
      submitted to IVM reached similar cleavage (48/80 - 60%) and embryonic development
      rates to the blastocyst stage (10/48 - 21%) as the results obtained with the BCB
      control group oocytes (45/77 - 58% and 08/45 - 18%, respectively). The aim of the
      second experiment was to determine the cleavage and blastocyst rates obtained
      from BCB+ oocytes undergoing IVM in the presence of BCB- oocytes at a ratio of
      10:1. COCs were recovered from slaughterhouse-derived ovaries and, after
      morphological evaluation, were randomised into two groups that were submitted to
      IVM either directly (1: control group) or submitted to the BCB test prior to IVM.
      After the BCB test, the COCs were classified as either BCB+ (blue cytoplasm) or
      BCB- (colourless cytoplasm) and then divided into four experimental groups: (2)
      BCB+; (3) BCB-; and (4) BCB+ matured in same IVM medium drop as (5) BCB- at a
      ratio of 10:1. After IVM (24 h), oocytes from the different experimental groups
      were submitted to in vitro fertilisation (IVF) and in vitro culture (IVC) under
      the same culture conditions until they reached the blastocyst stage (D7). With
      regards to the cleavage rate (48 h after IVF), only group 3 (102/229 - 44%)
      differed (P < 0.05) from the other groups [1 (145/241 - 60%); 2 (150/225 - 67%);
      4 (201/318 - 63%) and 5 (21/33 - 63%)]. On day 7, the embryos from group 2 (BCB+)
      achieved the highest blastocyst rate (46/150 - 31%) (P < 0.05) when compared with
      the embryo development capacity of the other experimental groups (1: 31/145 -
      21%; group 3: 17/102 - 17%; group 4: 46/201 - 23%; and group 5: 2/21 - 10%). In
      conclusion, submitting BCB+ oocytes that were separated from BCB- oocytes to IVM
      increases the rate of embryonic development to the blastocyst stage when compared
      to the control group, BCB- oocyte group, BCB+ paracrine group and BCB- paracrine
      group. The presence of non-competent oocytes during IVM, even in low proportion
      (1:10), reduces the capacity of competent oocytes to undergo embryo development
      and achieve blastocyst stage during IVC. 

PMID- 25943120
TI  - Measurement of cholinesterase enzyme activity before and after exposure to
      organophosphate pesticides in farmers of a suburb region of Mazandaran, a
      northern province of Iran.
AB  - INTRODUCTION: Accidental toxicity by organophosphate (OP) agents may occur among
      farmers during spraying season due to improper use and handling. Plasma
      cholinesterase (ChE) activity measurement is recommended to monitor the extent of
      exposure to the OP agent. The aim of the current study was to measure plasma ChE
      activity before and after exposure with OP pesticides. METHODS: This was a
      prospective study conducted on 36 farmers working in the farm field. The plasma
      ChE level was measured before spraying and 2 days and 8 weeks after spraying
      season and exposure to OP agent. Farmers were observed for clinical signs and
      symptoms of toxicity after exposure. RESULTS: Vertimac was the most common agent
      used by farmers followed by diazinon and chlorpyrifos. The plasma ChE level
      significantly decreased after exposure by over 50%. The level returned to
      preexposure level after 8 weeks. CONCLUSION: Exposure to OP pesticide is a major
      concern in the developing countries. More than 50% reduction in the plasma ChE
      activity after spraying is an alarming message for health-care system and policy
      makers. Furthermore, workplace evaluation, serial ChE monitoring, and appropriate
      training and education to exposed individuals would be initial important steps to
      avoid the toxicity or reduce the severity of poisoning.

PMID- 25943121
TI  - The impact of social networks on the relationship between functional impairment
      and depressive symptoms in older adults.
AB  - BACKGROUND: To examine the role of meaningful relationship characteristics,
      defined here as social network type, in relation to the association between
      functional impairment and depressive symptoms. METHODS: The sample included
      respondents aged 65 years and older (n = 26,401) from the fourth wave of the
      Survey of Health, Ageing and Retirement in Europe (SHARE). Respondents were
      classified into one of seven relationship network types (Distal Children (living
      at a distance), Proximal Family (living nearby), Spouse, Other Family, Friend,
      Other, and No Network) according to the predominant characteristics of their most
      meaningful relationships. A two-stage regression analysis was performed in which
      the number of depressive symptoms was first regressed on the extent of functional
      impairment and network type, controlling for sociodemographic characteristics,
      cognition, health, and country. In the second stage, variables representing the
      interactions between functional impairment and network type were considered.
      RESULTS: The compositional characteristics of respondents' relationships in later
      life, as defined by social network type, were associated with depressive
      symptoms. In particular, when experiencing functional impairment, those without
      any meaningful relationships were found to have more depressive symptoms when
      compared to all other network types. The findings underscore the importance of
      meaningful relationships for the mental health of older adults experiencing
      functional impairment as well as the risk of experiencing depression among those
      who maintain no personal social network. CONCLUSIONS: The study shows that
      differing constellations of meaningful relationships in later life yield
      different associations with mental health, especially when taking functional
      limitations into account.

PMID- 25943122
TI  - Disintegration of Sensorimotor Brain Networks in Schizophrenia.
AB  - BACKGROUND: Schizophrenia is a severe mental disorder associated with derogated
      function across various domains, including perception, language, motor,
      emotional, and social behavior. Due to its complex symptomatology, schizophrenia
      is often regarded a disorder of cognitive processes. Yet due to the frequent
      involvement of sensory and perceptual symptoms, it has been hypothesized that
      functional disintegration between sensory and cognitive processes mediates the
      heterogeneous and comprehensive schizophrenia symptomatology. METHODS: Here,
      using resting-state functional magnetic resonance imaging in 71 patients and 196
      healthy controls, we characterized the standard deviation in BOLD (blood-oxygen
      level-dependent) signal amplitude and the functional connectivity across a range
      of functional brain networks. We investigated connectivity on the edge and node
      level using network modeling based on independent component analysis and utilized
      the brain network features in cross-validated classification procedures. RESULTS:
      Both amplitude and connectivity were significantly altered in patients, largely
      involving sensory networks. Reduced standard deviation in amplitude was observed
      in a range of visual, sensorimotor, and auditory nodes in patients. The strongest
      differences in connectivity implicated within-sensorimotor and sensorimotor
      thalamic connections. Furthermore, sensory nodes displayed widespread alterations
      in the connectivity with higher-order nodes. We demonstrated robustness of
      effects across subjects by significantly classifying diagnostic group on the
      individual level based on cross-validated multivariate connectivity features.
      CONCLUSION: Taken together, the findings support the hypothesis of disintegrated
      sensory and cognitive processes in schizophrenia, and the foci of effects
      emphasize that targeting the sensory and perceptual domains may be key to enhance
      our understanding of schizophrenia pathophysiology.

PMID- 25943123
TI  - Psychopathology of Lived Time: Abnormal Time Experience in Persons With
      Schizophrenia.
AB  - Abnormal time experience (ATE) in schizophrenia is a long-standing theme of
      phenomenological psychopathology. This is because temporality constitutes the
      bedrock of any experience and its integrity is fundamental for the sense of
      coherence and continuity of selfhood and personal identity. To characterize ATE
      in schizophrenia patients as compared to major depressives we interviewed, in a
      clinical setting over a period of 15 years, 550 consecutive patients affected by
      schizophrenic and affective disorders. Clinical files were analyzed by means of
      Consensual Qualitative Research (CQR), an inductive method suited to research
      that requires rich descriptions of inner experiences. Of the whole sample, 109
      persons affected by schizophrenic (n = 95 acute, n = 14 chronic) and 37 by major
      depression reported at least 1 ATE. ATE are more represented in acute (N = 109
      out of 198; 55%) than in chronic schizophrenic patients (N = 14 out of 103; 13%).
      The main feature of ATE in people with schizophrenia is the fragmentation of time
      experience (71 out of 109 patients), an impairment of the automatic and
      prereflexive synthesis of primal impression-retention-protention. This includes 4
      subcategories: disruption of time flowing, deja vu/vecu, premonitions about
      oneself and the external world. We contrasted ATE in schizophrenia and in major
      depression, finding relevant differences: in major depressives there is no
      disarticulation of time experience, rather timelessness because time lacks
      duration, not articulation. These core features of the schizophrenic pheno
      phenotype may be related to self-disorders and to the manifold of characteristic
      schizophrenic symptoms, including so called bizarre delusions and verbal-acoustic
      hallucinations. 

PMID- 25943125
TI  - Social Cognition Psychometric Evaluation: Results of the Initial Psychometric
      Study.
AB  - Measurement of social cognition in treatment trials remains problematic due to
      poor and limited psychometric data for many tasks. As part of the Social
      Cognition Psychometric Evaluation (SCOPE) study, the psychometric properties of 8
      tasks were assessed. One hundred and seventy-nine stable outpatients with
      schizophrenia and 104 healthy controls completed the battery at baseline and a 2
      4-week retest period at 2 sites. Tasks included the Ambiguous Intentions
      Hostility Questionnaire (AIHQ), Bell Lysaker Emotion Recognition Task (BLERT),
      Penn Emotion Recognition Task (ER-40), Relationships Across Domains (RAD),
      Reading the Mind in the Eyes Task (Eyes), The Awareness of Social Inferences Test
      (TASIT), Hinting Task, and Trustworthiness Task. Tasks were evaluated on: (i)
      test-retest reliability, (ii) utility as a repeated measure, (iii) relationship
      to functional outcome, (iv) practicality and tolerability, (v) sensitivity to
      group differences, and (vi) internal consistency. The BLERT and Hinting task
      showed the strongest psychometric properties across all evaluation criteria and
      are recommended for use in clinical trials. The ER-40, Eyes Task, and TASIT
      showed somewhat weaker psychometric properties and require further study. The
      AIHQ, RAD, and Trustworthiness Task showed poorer psychometric properties that
      suggest caution for their use in clinical trials. 

PMID- 25943126
TI  - Cerebral oligodendroglioma mimicking intraventricular neoplasia in three dogs.
AB  - Oligodendroglioma is one of the most common primary central nervous system
      neoplasms of dogs. It is often diagnosed in older, brachycephalic breeds, and
      although its typical clinical features and neuroanatomic location have been well
      described, less common presentations may hinder its diagnosis. We describe 3
      cases of canine cerebral oligodendroglioma that clinically and grossly present as
      intraventricular tumors. Histologic findings in all cases were typical of
      oligodendroglioma. Neoplastic cells were uniformly immunoreactive for Olig2 and
      negative for neuron-specific enolase, neurofilament, and glial fibrillary acidic
      protein. In addition to the immunopositivity for Olig2, a cluster of
      morphologically distinct neoplastic cells in one of the cases was immunoreactive
      for synaptophysin, and the case was diagnosed as an oligodendroglioma with
      neurocytic differentiation. Based on these findings, oligodendroglioma should be
      included as a differential diagnosis for intraventricular neoplasia in dogs.
      Furthermore, oligodendroglioma with ventricular involvement should be
      differentiated from central neurocytoma by immunohistochemistry.

PMID- 25943124
TI  - Endophenotypes in Schizophrenia for the Perinatal Period: Criteria for
      Validation.
AB  - Endophenotypes are disease-associated phenotypes that are thought to reflect the
      neurobiological or other mechanisms that underlie the more overt symptoms of a
      psychiatric illness. Endophenotypes have been critical in understanding the
      genetics, neurobiology, and treatment of schizophrenia. Because psychiatric
      illnesses have multiple causes, including both genetic and nongenetic risk
      factors, an endophenotype linked to one of the mechanisms may be expressed more
      frequently than the disease itself. However, in schizophrenia research,
      endophenotypes have almost exclusively been studied in older adolescents or
      adults who have entered or passed through the age of risk for the disorder. Yet,
      schizophrenia is a neurodevelopmental disorder where prenatal development starts
      a cascade of brain changes across the lifespan. Endophenotypes have only
      minimally been utilized to explore the perinatal development of vulnerability.
      One major impediment to the development of perinatally-useful endophenotypes has
      been the established validity criteria. For example, the criterion that the
      endophenotype be more frequently present in those with disease than those without
      is difficult to demonstrate when there can be a decades-long period between
      endophenotype measurement and the age of greatest risk for onset of the disorder.
      This article proposes changes to the endophenotype validity criteria appropriate
      to perinatal research and reviews how application of these modified criteria
      helped identify a perinatally-usable phenotype of risk for schizophrenia, P50
      sensory gating, which was then used to propose a novel perinatal primary
      prevention intervention. 

PMID- 25943127
TI  - Assessment of platelet function in healthy sedated cats using three whole blood
      platelet function tests.
AB  - The objectives of this study were to establish feline references intervals for 3
      commercial whole blood platelet function test analyzer systems: Multiplate
      analyzer (MP; Roche Diagnostics International Ltd., Rotkreuz, Switzerland),
      Platelet Function Analyzer-100 (PF: Siemens Canada, Mississauga, Ontario,
      Canada), and Plateletworks Combo-25 kit (PW; Helena Laboratories, Beaumont, TX).
      Venipuncture was performed on 55 healthy sedated cats, and platelet aggregation
      in response to adenosine diphosphate (ADP), collagen (COL), and arachidonic acid
      (AA; MP only) was assessed using citrated blood. For the MP analyzer, median (95%
      confidence intervals [CIs]) area under curve (Units) for ADP, COL, and AA
      agonists were 87 (11-176), 81 (32-129), and 91 (59-129), respectively. For the PF
      analyzer, median (95% CIs) closure time, using COL-ADP cartridges, was 69 (46-89)
      sec. For the PW assay, median (95% CIs) percent aggregations for ADP and COL
      agonists were 71 (18-92) and 49 (9-96), respectively, using impedance hematology
      analyzer platelet counts, and 94 (25-98) and 68 (14-119), respectively, using
      flow cytometry hematology analyzer platelet counts. There were low correlations
      between the PF analyzer (COL-ADP cartridge) and MP analyzer (COL agonist; rho =
      0.11), and between the PF analyzer (COL-ADP cartridge) and PW assay (COL agonist
      using impedance platelet counts; rho = 0.14). The PW assay percent aggregations
      using impedance and flow cytometric platelet counts were correlated for both ADP
      (rho = 0.64) and COL (rho = 0.64) agonists. Platelet function testing using these
      tests are feasible in cats, but 95% CIs are wide, so single results may be
      difficult to interpret. Platelet counting by impedance or flow cytometry may be
      used for the PW assay but are not interchangeable.

PMID- 25943128
TI  - Emydid herpesvirus 1 infection in northern map turtles (Graptemys geographica)
      and painted turtles (Chrysemys picta).
AB  - A captive, juvenile, female northern map turtle (Graptemys geographica) was found
      dead following a brief period of weakness and nasal discharge. Postmortem
      examination identified pneumonia with necrosis and numerous epithelial,
      intranuclear viral inclusion bodies, consistent with herpesviral pneumonia.
      Similar intranuclear inclusions were also associated with foci of hepatocellular
      and splenic necrosis. Polymerase chain reaction (PCR) screening of fresh, frozen
      liver for the herpesviral DNA-dependent DNA polymerase gene yielded an amplicon
      with 99.2% similarity to recently described emydid herpesvirus 1 (EmyHV-1).
      Molecular screening of turtles housed in enclosures that shared a common
      circulation system with the affected map turtle identified 4 asymptomatic, EmyHV
      1 PCR-positive painted turtles (Chrysemys picta) and 1 asymptomatic northern map
      turtle. Herpesvirus transmission between painted and map turtles has been
      previously suggested, and our report provides the molecular characterization of a
      herpesvirus in asymptomatic painted turtles that can cause fatal herpesvirus
      associated disease in northern map turtles.

PMID- 25943130
TI  - Pneumonia and bacteremia in a golden-headed lion tamarin (Leontopithecus
      chrysomelas) caused by Klebsiella pneumoniae subsp. pneumoniae during a
      translocation program of free-ranging animals in Brazil.
AB  - Klebsiella pneumoniae is an important emerging pathogen in humans, particularly
      the invasive hypermucoviscosity (HMV) phenotype. In addition, the organism is an
      important public health concern because of nosocomial infections and
      antimicrobial resistance. Nonhuman primates in captivity are susceptible to
      Klebsiella, particularly when a stress factor is involved. Infections vary
      depending on the species but can cause significant morbidity and mortality in
      these animals. The objective of this study was to describe a case of
      bronchopneumonia and bacteremia caused by Klebsiella pneumoniae in a free-ranging
      golden-headed lion tamarin (Leontopithecus chrysomelas) caught and maintained in
      quarantine during a translocation program for conservation purposes. An adult
      male, that had showed emaciation and apathy, was clinically examined and, despite
      being provided supportive therapy, died 2 days after onset of clinical signs. At
      postmortem examination, generalized bilateral pneumonia and pericarditis were
      observed. Tissue samples were fixed in 10% formalin for histology, and pulmonary
      tissues and cardiac blood were collected for microbiologic diagnostic procedures.
      Bacteria that were shown to be HMV K. pneumoniae subsp. pneumoniae strains were
      isolated from the pulmonary fluids and cardiac blood in pure cultures. Severe
      bronchopneumonia was the main pathological finding. The consequences of the
      confirmed presence of the HMV phenotype of K. pneumoniae subsp. pneumoniae in
      this wildlife species for human, animal, and ecosystem health should be
      determined. These results demonstrate the importance of quarantine and potential
      pathogen screening during wildlife translocation procedures.

PMID- 25943131
TI  - Special section guest editorial: Laser applications in life sciences.

PMID- 25943129
TI  - A new trivalent SnSAG surface antigen chimera for efficient detection of
      antibodies against Sarcocystis neurona and diagnosis of equine protozoal
      myeloencephalitis.
AB  - Enzyme-linked immunosorbent assays (ELISAs) based on the SnSAG surface antigens
      of Sarcocystis neurona provide reliable detection of infection by the parasite.
      Moreover, accurate serodiagnosis of equine protozoal myeloencephalitis (EPM) is
      achieved with the SnSAG ELISAs by measuring antibodies in serum and cerebrospinal
      fluid (CSF) to reveal active infection in the central nervous system. Two
      independent ELISAs based on recombinant (r)SnSAG2 or a chimeric fusion of SnSAG3
      and SnSAG4 (rSnSAG4/3) are currently used together for EPM serodiagnosis to
      overcome varied antibody responses in different horses. To achieve reliable
      antibody detection with a single ELISA instead of 2 separate ELISAs, rSnSAG2 was
      fused with rSnSAG4/3 into a single trivalent protein, designated rSnSAG2/4/3.
      Paired serum and CSF from 163 horses were tested with all 3 ELISAs. When the
      consensus antibody titers obtained with the rSnSAG2 and rSnSAG4/3 ELISAs were
      compared to the single SAG2/4/3 ELISA titers, Spearman rank correlation
      coefficients of rho = 0.74 and rho = 0.90 were obtained for serum and CSF,
      respectively, indicating strong agreement between the tests. When the rSnSAG2 and
      rSnSAG4/3 consensus serum-to-CSF titer ratio was compared to the rSnSAG2/4/3
      serum-to-CSF titer ratio, the Spearman correlation coefficient was rho = 0.87,
      again signifying strong agreement. Importantly, comparing the diagnostic
      interpretation of the serum-to-CSF titer ratios yielded a Cohen kappa value of
      0.77. These findings suggest that the single ELISA based on the trivalent
      rSnSAG2/4/3 will provide serologic and diagnostic results that are highly
      comparable to the consensus of the 2 independent ELISAs based on rSnSAG2 and
      rSnSAG4/3.

PMID- 25943132
TI  - Image distortion and its correction in linear galvanometric mirrors-based laser
      scanning microscopy.
AB  - To simplify imaging focusing and calibration tasks, a laser-scanning microscope
      needs to scan ata moderate frame rate. The inertia of a galvanometric scanner
      leads to time delays when following external commands, which subsequently
      introduces image distortions that deteriorate as scan frequency increases.
      Sinusoidal and triangular waveforms were examined as fast axis driving patterns.
      The interplay among driving pattern, frequency, sampling rate, phase shift,
      linear scanning range, and their effect on reconstructed images was discussed.
      Utilizing position feedback from the linear galvo scanners, the effect of
      response time could be automatically compensated in real time. Precompensated
      triangular driving waveform offered the least amount of image distortion.

PMID- 25943133
TI  - Dynamics of statistically confident particle sizes and concentrations in blood
      plasma obtained by the dynamic light scattering method.
AB  - The work is devoted to the study of sizes and concentrations of proteins, and
      their aggregates in blood plasma samples, using static and dynamic light
      scattering methods. A new approach is proposed based on multiple repetition of
      measurements of intensity size distribution and on counting the number of
      registrations of different sizes, which made it possible to obtain statistically
      confident particle sizes and concentrations in the blood plasma. It was revealed
      that statistically confident particle sizes in the blood plasma were stable
      during 30 h of observations, whereas the concentrations of particles of different
      sizes varied as a result of redistribution of material between them owing to the
      protein degradation processes.

PMID- 25943134
TI  - The Journal of School Nursing -SAGE Writing Awards.

PMID- 25943135
TI  - Kinetico-Mechanistic Studies of Nucleoside and Nucleotide Substitution Reactions
      of Co(III) Complexes of Fully Alkylated Cyclen.
AB  - The solution chemistry of complex [Co{(Me)2(MU-ET)cyclen}(H2O)2](3+) containing a
      fully substituted tetraammine ligand designed for the avoidance of base
      conjugated substitution mechanisms in the 6-8 pH range has been studied. The
      study should shed some light on the possible involvement of such Co(III) skeleton
      in inert interactions with biomolecules. The reactivity and speciation of the
      complex has been found similar to that of the parent cyclen derivative with the
      presence of mono- and bis-hydroxo-bridged species; at pH < 7.1, all reactivity
      has been found to be related to the aqua/hydroxo monomeric complexes. Under these
      pH conditions, the substitution reactions of the aqua/hydroxo ligands by
      chloride, inorganic phosphate, thymidine, cytidine 5'-monophosphate (5'-CMP), and
      thymidine-5'-monophosphate (5'-TMP) have been studied at varying conditions;
      ionic strength has been kept at 1.0 NaClO4 due to the high concentration of 2-(N
      morpholino)ethanesulfonic acid (MES) or N-2-hydroxyethylpiperazine-N'-2
      ethanesulfonic acid (HEPES) used to ensure buffering. Except for chloride, the
      process occurs neatly in a one or two step process, showing dissociatively
      activated substitution mechanisms, having in general large DeltaH(?), positive
      DeltaS(?), and values of DeltaV(?) close to those corresponding to the liberation
      of an aqua ligand to the reaction medium. The actuation of noticeable encounter
      complex formation equilibrium constants has been found to be the determinant for
      the reactions with nucleosides and nucleotides, a clear indication of the
      relevance of hydrogen-bonding interactions in the reactivity of these molecules,
      even in this highly ionic strength medium. For the substitution of the active
      aqua/hydroxo ligands with 5'-TMP, the first substitution reaction produces an
      Nthymine-bound 5'-TMP complex that evolves to a bis-5'-TMP with an
      Nthymine,Ophosphate-bonding structure. The formation of outer-sphere complexes
      between the dangling phosphate group of the Nthymine-bound 5'-TMP and the thymine
      moiety of another entering 5'-TMP has been found to be responsible for this fact,
      which leaves only the phosphate group for coordination available. 

PMID- 25943136
TI  - Goal setting in cancer rehabilitation and relation to quality of life among women
      with gynaecological cancer.
AB  - BACKGROUND: Rehabilitation should be integrated in the routine cancer care of
      women treated for gynaecological cancers. Goal setting is expected to facilitate
      the process through patient involvement and motivation. Our knowledge about goal
      setting in cancer rehabilitation is, however, sparse. OBJECTIVES: This study
      aimed to: 1) analyse rehabilitation goals defined during hospital-based
      rehabilitation in patients with gynaecological cancer, with regard to number,
      category, changes over time, and differences between cancer diagnosis, and 2)
      analyse the association between health-related quality of life and goals defined
      for rehabilitation. MATERIAL AND METHODS: Consecutively, all patients treated
      surgically for endometrial, ovarian, and cervical cancer were invited for
      hospital-based rehabilitation at Odense University Hospital, Denmark, including
      two sessions at the hospital one and three months following surgery and two phone
      calls for follow-up. Questionnaires from the EORTC were used to prepare patients
      and facilitate individual goal setting with definitions of up to three goals. All
      goals were grouped into six categories. RESULTS: A total of 151 (63%) patients
      accepted the invitation including 50 endometrial, 65 ovarian, and 36 cervical
      cancers patients. All patients defined goals at the first session, 76.4% defined
      three goals, 21.9% two, and 1.6% had one goal. Physical goals decreased over time
      but were the most frequent at both sessions (98% and 89%). At both sessions, the
      social and emotional categories were the second and third most frequent among
      patients with endometrial and ovarian cancer. Sexual issues were dominant among
      the cervical cancer patients. Regression analysis showed significant association
      between quality of life scores and goal setting within the social and emotional
      domains. CONCLUSION: Goal setting seemed feasible in all problem areas. The EORTC
      questionnaires were helpful during the process although expectations of the sub
      scores being predictive of which areas to address were not convincing.

PMID- 25943137
TI  - Microbial synthesis of Flower-shaped gold nanoparticles.
AB  - The shape of nanoparticles has been recognized as an important attribute that
      determines their applicability in various fields. The flower shape (F-shape) has
      been considered and is being focused on, because of its enhanced properties when
      compared to the properties of the spherical shape. The present study proposed the
      microbial synthesis of F-shaped gold nanoparticles within 48 h using the
      Bhargavaea indica DC1 strain. The F-shaped gold nanoparticles were synthesized
      extracellularly by the reduction of auric acid in the culture supernatant of B.
      indica DC1. The shape, size, purity, and crystalline nature of F-shaped gold
      nanoparticles were revealed by various instrumental techniques including UV-Vis,
      FE-TEM, EDX, elemental mapping, XRD, and DLS. The UV-Vis absorbance showed a
      maximum peak at 536 nm. FE-TEM revealed the F-shaped structure of nanoparticles.
      The EDX peak obtained at 2.3 keV indicated the purity. The peaks obtained on XRD
      analysis corresponded to the crystalline nature of the gold nanoparticles. In
      addition, the results of elemental mapping indicated the maximum distribution of
      gold elements in the nanoproduct obtained. Particle size analysis revealed that
      the average diameter of the F-shaped gold nanoparticles was 106 nm, with a
      polydispersity index (PDI) of 0.178. Thus, the methodology developed for the
      synthesis of F-shaped gold nanoparticles is completely green and economical. 

PMID- 25943138
TI  - Ebola virus disease - gaps in knowledge and practice among healthcare workers in
      Lagos, August 2014.
AB  - OBJECTIVE: Healthcare workers (HCWs) play pivotal roles in outbreak responses.
      Ebola virus disease (EVD) outbreak spread to Lagos, Nigeria, in July 2014,
      infecting 11 HCWs (case fatality rate of 45%). This study was conducted during
      the outbreak to assess HCWs' EVD-related knowledge and practices. METHODS: A
      health facility-based cross-sectional study was conducted among HCWs across Lagos
      State using stratified sampling technique. An interviewer-administered
      questionnaire was administered to elicit respondents' socio-demographic
      characteristics, knowledge and practices. A checklist assessing health facility's
      level of preparedness and HCWs' EVD-related training was employed. HCWs'
      knowledge and practices were scored and classified as either good or poor.
      Multivariate analysis was performed with confidence interval set at 95%. RESULTS:
      A total of 112 health facilities with 637 HCWs were recruited. Mean age of
      respondents was 40.1 +/- 10.9 years. Overall, 72.5% had good knowledge; doctors
      knew most. However, only 4.6% of HCWs reported good practices. 16.6% reported
      having been trained in identifying suspected EVD patient(s); 12.2% had a triaging
      area for febrile patients in their facilities. Higher proportions of HCWs with
      good knowledge and training reported good practices. HCWs with EVD-related
      training were three times more likely to adopt good practices. CONCLUSION: Lagos
      State HCWs had good knowledge of EVD without a corresponding level of good
      practices. Training was a predictor of good practices.

PMID- 25943140
TI  - H2A.Z mediates different aspects of chromatin function and modulates flowering
      responses in Arabidopsis.
AB  - Eukaryotic organisms have canonical histones and a number of histone variants
      that perform specialized functions and confer particular structural properties to
      the nucleosomes that contain them. The histone H2A family comprises several
      variants, with H2A.Z being the most evolutionarily conserved. This variant is
      essential in eukaryotes and has emerged as a key player in chromatin function,
      performing an essential role in gene transcription and genome stability. During
      recent years, biochemical, genetic and genomic studies have begun to uncover the
      role of several ATP-dependent chromatin-remodeling complexes in H2A.Z deposition
      and removal. These ATPase complexes are widely conserved from yeast to mammals.
      In Arabidopsis there are homologs for most of the subunits of these complexes,
      and their functions are just beginning to be unveiled. In this review, we discuss
      the major contributions made in relation to the biology of the H2A.Z in plants,
      and more specifically concerning the function of this histone variant in the
      transition from vegetative to reproductive development. Recent advances in the
      understanding of the molecular mechanisms underlying the H2A.Z-mediated
      modulation of the floral transition, and thermosensory flowering responses in
      particular, are discussed. The emerging picture shows that plants contain
      chromatin-remodeling complexes related to those involved in modulating the
      dynamics of H2A.Z in other eukaryotes, but their precise biochemical nature
      remains elusive. 

PMID- 25943141
TI  - In the backwater of convective dialysis: decreased 25-hydroxyvitamin D levels
      following the switch to online hemodiafiltration.
AB  - BACKGROUND/AIMS: Vitamin D deficiency and elevated serum fibroblast growth factor
      23 (FGF23) levels are hallmark features and surrogate markers of adverse clinical
      outcomes in patients with chronic kidney disease (CKD). Convection of molecules
      over the dialysis membrane during online hemodiafiltration (ol-HDF) increases the
      removal of larger waste molecules compared with traditional high-flux
      hemodialysis (HD). The primary aim of this study was to explore the long-term
      impact of ol-HDF on serum 25(OH)D and FGF23. METHOD: An observational,
      prospective, noncomparator study including 35 patients who were switched from HD
      to ol-HDF. Serum 25(OH)D and FGF23 were measured at baseline (i.e., time of
      switch to ol-HDF) and at 6, 12, and 24 months. RESULTS: At follow-up time points,
      there was a significant reduction in serum 25(OH)D compared with baseline
      (p<0.0001) whereas FGF23 was unaltered (p>0.05). The decrease in 25(OH)D was more
      prominent in individuals with higher baseline 25(OH)D levels. CONCLUSION: Ol-HDF
      may lower systemic 25(OH)D levels by convective mechanisms although the clinical
      significance remains unknown. Further controlled studies are warranted to
      replicate these findings in larger patient cohorts.

PMID- 25943143
TI  - The relation of mean platelet volume with microalbuminuria and glomerular
      filtration rate in obese individuals without other metabolic risk factors: the
      role of platelets on renal functions.
AB  - INTRODUCTION: Mean platelet volume (MPV) is an indirect indicator of platelet
      activity that plays a major role in the pathogenesis of endothelial injury. Obese
      individuals have higher microalbuminuria which is the initial step of renal
      endothelial injury. We aimed to analyze the relation of microalbuminuria and MPV
      in obese individuals without metabolic risk factors. METHODS: A total of 290
      obese individuals (body mass index (BMI)>30 kg/m2) without an accompanying
      chronic disorder, and 204 nonobese healthy subjects were enrolled into the study.
      All participants underwent physical examination. Biochemical, hemogram, and
      hormonal parameters along with urine albumin analysis were performed. Glomerular
      filtration rate (GFR) was measured by Cockcroft-Gault (GFRC&G), modification of
      diet in renal disease (MDRD). The BMI was calculated as weight/height2 (kg/m2).
      Logistic regression analysis was used to analyze relation of variables. RESULTS:
      The patient group consisted of 171 (59%) female (mean age: 37.15+/-8.05 years)
      and 119 (41%) male (mean age 38.98+/-10.68 years) obese individuals. 130 (63.7%)
      age matched female (mean age 36.18+/-8.26 years) and 74 (36.3%) age matched male
      (mean age 36.49+/-10.25 years) controls were assigned to the control group. There
      was a significant difference between groups with regard to BMI, spot
      microalbuminuria, spot urine microalbuminuria/creatinine ratio but not with to
      MPV and spot urine creatinine (p: 0.01, 0.004, 0.002; respectively). GFR measured
      by MDRD and Cockcroft-Gault formula were significantly higher in the obese group
      (p<0.001 for both). Correlation analysis revealed a significant correlation
      between BMI and spot urine microalbuminuria, spot urine
      microalbuminuria/creatinine ratio, GFR (Cockcroft-Gault Formula), Homeostasis
      Model Assessment of Insulin resistance (HOMA-IR), insulin, C-peptide, diastolic
      blood pressure, glucose, uric acid, total cholesterol, low density lipoprotein
      (LDL)-cholesterol, c-reactive protein (CRP), thyroid stimulating hormone (TSH),
      leukocyte count, platelet count. MPV was inversely and significantly correlated
      with spot urine creatinine, systolic blood pressure, triglyceride, C-peptide, and
      platelet count. Mean urea, creatinine, uric acid, triglyceride, total
      cholesterol, LDL-cholesterol, insulin, C-peptide, HOMA-IR were significantly
      higher in obese male individuals while obese female individuals had higher levels
      of mean high density lipoprotein (HDL), CRP, TSH, platelet count, spot urine
      microalbumin/creatinine rate, and GFR measured by MDRD. CONCLUSIONS: Obese
      individuals have higher microalbuminuria and nonsignificantly elevated MPV,
      however, urine albumin loss is independent of MPV.

PMID- 25943142
TI  - Tubular dysfunction in renal transplant patients using sirolimus or tacrolimus.
AB  - BACKGROUND: Tubular dysfunction is prevalent among kidney transplant patients
      using calcineurin inhibitors, but our knowledge of the tubular effects of mTOR
      inhibitors is more limited. METHODS: 60 kidney transplant outpatients using
      either the calcineurin inhibitor tacrolimus or the mTOR inhibitor sirolimus were
      investigated for renal tubular dysfunction. Proximal tubule function was assessed
      by quantification of albumin and beta2-microglobulin, tubular reabsorption of
      phosphate and fractional excretion of bicarbonate. Distal tubular function was
      evaluated by water deprivation test and by urinary acidification test using
      furosemide and fludrocortisone for pH, ammonium and titratable acidity
      measurements. RESULTS: The prevalence of distal renal tubular acidosis (dRTA) was
      17% for both treatment groups. 70% of patients treated with sirolimus and 94%
      using tacrolimus presented with urine concentrating defect (p=0.04). CONCLUSION:
      Distal RTA and urine concentrating defect were highly prevalent after kidney
      transplantation both in the sirolimus and tacrolimus treated patients.
      Acidification test was essential for the appropriate diagnosis of dRTA while
      dipstick urine specific gravity test was able to detect urine concentrating
      defect in this population.

PMID- 25943139
TI  - Left-right asymmetry in the light of TOR: An update on what we know so far.
AB  - The internal left-right (LR) asymmetry is a characteristic that exists throughout
      the animal kingdom from roundworms over flies and fish to mammals. Cilia, which
      are antenna-like structures protruding into the extracellular space, are involved
      in establishing LR asymmetry during early development. Humans who suffer from
      dysfunctional cilia often develop conditions such as heterotaxy, where internal
      organs appear to be placed randomly. As a consequence to this failure in
      asymmetry development, serious complications such as congenital heart defects
      (CHD) occur. The mammalian (or mechanistic) target of rapamycin (mTOR) pathway
      has recently emerged as an important regulator regarding symmetry breaking. The
      mTOR pathway governs fundamental processes such as protein translation or
      metabolism. Its activity can be transduced by two complexes, which are called
      TORC1 and TORC2, respectively. So far, only TORC1 has been implicated with
      asymmetry development and appears to require very precise regulation. A number of
      recent papers provided evidence that dysregulated TORC1 results in alterations of
      motile cilia and asymmetry defects. In here, we give an update on what we know so
      far of mTORC1 in LR asymmetry development. 

PMID- 25943144
TI  - Non-functioning pituitary macroadenoma in a child with neurofibromatosis type 1.

PMID- 25943145
TI  - The Effect of Proanthocyanidins on Growth and Alcoholic Fermentation of Wine
      Yeast under Copper Stress.
AB  - Proanthocyanidins (PAs) derived from the grape skin, as well as from grape seeds,
      grape stems, are an important group of polyphenols in wine. The aim of this study
      was to understand the effect of PAs (0.1, 1.0 g/L) on growth and alcoholic
      fermentation of 2 strains of Saccharomyces cerevisiae (commercial strain FREDDO
      and newly selected strain BH8) during copper-stress fermentation, using a simple
      model fermentation system. Our results showed that both PAs and Cu(2+) could pose
      significant inhibition effects on the growth of yeast cells, CO2 release, sugar
      consumption, and ethanol production during the initial phase of the fermentation.
      Compared to PAs, Cu(2+) performed more obvious inhibition on the yeast growth and
      fermentation. However, adding 1.0 g/L PAs increased in the vitality and
      metabolism activity of yeast cells at the mid-exponential phase of fermentation
      in the mediums with no copper and 0.1 mM Cu(2+) added, shortened the period of
      wine fermentation, and decreased the copper residues. It indicated that PAs could
      improve the ability of wine yeast to resist detrimental effects under copper
      stress fermentation condition, maintaining cells metabolic activity, and
      fermentation could be controlled by manipulating PAs supplementation. 

PMID- 25943146
TI  - Validation of Hospitalization Impact Scale among families with children
      hospitalized for cancer treatment.
AB  - AIM: To make further modifications to and validate the psychometric properties of
      the Hospitalization Impact Scale. BACKGROUND: A child's repeated and prolonged
      hospitalization for cancer treatment can result in great changes for the entire
      family. A hospitalization-specific screening tool is needed to help clinical
      nurses identify families who are experiencing major impacts during their child's
      hospitalization. DESIGN: A cross-sectional study was employed to examine the
      psychometric properties of the Hospitalization Impact Scale. METHOD: The sample
      consisted of 253 families with children hospitalized for cancer treatment in four
      paediatric oncology departments in four hospitals in mainland China from
      September 2013 - March 2014. Parents completed the 36-item Hospitalization Impact
      Scale, demographic measures and the Family Impact Module of the Pediatric Quality
      of Life Inventory. Reliability, construct validity, known-group validity and
      concurrent validity were examined. RESULT: The revised Hospitalization Impact
      Scale included six factors containing 34 items. It demonstrated sound concurrent
      validity with the Family Impact Module of the Pediatric Quality of Life Inventory
      and excellent internal consistency. CONCLUSION: The revised Hospitalization
      Impact Scale met the standard psychometric criteria for reliability and validity.
      Thus, it could be applied in paediatric oncology departments to help nurses
      assess and identify families experiencing major impacts during a child's
      hospitalization for cancer treatment.

PMID- 25943147
TI  - Blockade of Extracellular HMGB1 Suppresses Xenoreactive B Cell Responses and
      Delays Acute Vascular Xenogeneic Rejection.
AB  - Blockade of extracellular high mobility group box 1 (HMGB1) can significantly
      prolong murine cardiac allograft survival. Here, we determined the role of HMGB1
      in xenotransplantation. Sprague-Dawley rat hearts were transplanted
      heterotopically into BALB/c mice. Xenografts without any treatment developed
      predominant acute vascular rejection within 6 days. Both passively released HMGB1
      from xenografts and actively secreted HMGB1 from infiltrated immune cells were
      significantly increased after xenotransplantation. HMGB1-neutralizing antibody
      treatment significantly prolonged xenograft survival and attenuated pathologic
      damage, immune cell infiltration, and HMGB1 expression and release in the
      xenografts. Compared to control IgG treatment evaluated at study endpoint,
      treatment with HMGB1-neutralizing antibody markedly suppressed xenoreactive B
      cell responses, as evidenced by the significant inhibition of anti-rat antibody
      production and deposition in xenografts at Day 6 posttransplant. Furthermore,
      treatment with anti-HMGB1 antibody suppressed B cell activation and reduced IFN
      gamma and IL-17A production after xenotransplantation. These results demonstrate
      for the first time that HMGB1 plays an important role in mediating acute
      xenograft rejection. Thus, we have shown that neutralization of extracellular
      HMGB1 can significantly inhibit xenoreactive B cell responses and delay xenograft
      rejection in a rat-to-mouse model of xenotransplantation, uncovering new insights
      in the role of HMGB1 in transplantation. 

PMID- 25943148
TI  - Age and growth of mangrove red snapper Lutjanus argentimaculatus at its cool
      water-range limits.
AB  - This study investigates the age and growth of Lutjanus argentimaculatus at its
      southern (cooler) range limits in eastern Australia. Specimens were collected
      from New South Wales and southern Queensland between November 2011 and December
      2013. Fork lengths (LF ) ranged from 190 to 1019 mm, and ages ranged from 2+ to
      57+ years. Growth was described by the von Bertalanffy growth function with
      coefficients Linfinity = 874.92 mm, K = 0.087 year(-1) and t0 = -2.76 years.
      Estimates of the instantaneous natural mortality rate (M) ranged from 0.072 to
      0.25. The LF (mm) and mass (W; g) relationship was represented by the equation:
      W=2.647*10-5LF2.92. The maximum age of 57+ years is the oldest reported for any
      lutjanid and comparisons with tropical studies suggest that the age-based
      demography of L. argentimaculatus follows a latitudinal gradient. High maximum
      ages and low natural mortality rates indicate considerable vulnerability to
      overexploitation at the species' cool-water-range limits. These results
      demonstrate the need to identify underlying processes driving latitudinal
      gradients in fish demography. 

PMID- 25943149
TI  - Biochemical composition of the ovarian fluid and its effects on the fertilization
      capacity of turbot Scophthalmus maximus during the spawning season.
AB  - This study investigated the biochemical composition of ovarian fluid and its
      effect on the fertilization capacity of turbot Scophthalmus maximus during the
      spawning season. The fertilization rate and pH of ovarian fluid varied throughout
      the spawning season, with the highest values recorded at the mid-season. Positive
      correlations were found between the fertilization rate and the ovarian fluid pH.
      The composition of major inorganic ions (Na(+) , K(+) , Ca(2+) and Cl(-) ) showed
      no significant changes during the spawning season. Alkaline phosphatase (AKP)
      activity was significantly higher during mid-season than other seasons. The
      lowest levels of protein, acid phosphatase (ACP) and aspartate aminotransferase
      (AAT) were in the ovarian fluid released at the mid-season. Moreover, significant
      relationships were observed between the fertilization rate and the levels of
      protein, ACP, AKP and AAT. These observations suggest that the biochemical
      profile of ovarian fluid affects the insemination microenvironment as well as the
      fertilization capacity of S. maximus eggs. Determination of such profiles may
      prove to be a useful strategy to improve S. maximus breeding techniques. 

PMID- 25943150
TI  - High-density aggregations of rodlet cells in the gonads of Greenland halibut
      Reinhardtius hippoglossoides, a deep-water marine flatfish.
AB  - Large aggregations of rodlet cells in the gonads of male and female Greenland
      halibut Reinhardtius hippoglossoides are reported for the first time. These
      rodlet cells were not arranged epithelially but rather were found throughout the
      connective tissue between oocytes (females) or within lymphatic spaces between
      testicular lobules (males). The reason for large aggregations of rodlet cells in
      the gonads and not other tissues of this species is uncertain. 

PMID- 25943151
TI  - Evaluating the resolution power of new microsatellites for species identification
      and stock delimitation in the Cape hakes Merluccius paradoxus and Merluccius
      capensis (Teleostei: Merlucciidae).
AB  - The utility of 15 new and 17 previously published microsatellite markers was
      evaluated for species identification and stock delimitation in the deep-water
      hake Merluccius paradoxus and the shallow-water hake Merluccius capensis. A total
      of 14 microsatellites were polymorphic in M. paradoxus and 10 in M. capensis. Two
      markers could individually discriminate the species using Bayesian clustering
      methods and a statistical power analysis showed that the set of markers for each
      species is likely to detect subtle genetic differentiation (FST < 0.006) that
      will be valuable to delimit and characterize genetic stocks. 

PMID- 25943152
TI  - Discovery of a pupping site and nursery for critically endangered green sawfish
      Pristis zijsron.
AB  - A pilot study targeting sawfishes in the southern Pilbara region of Western
      Australia, which is undergoing a major expansion in human activity, was conducted
      using gillnets during April and October 2011 in the Ashburton Estuary and
      adjacent mangrove creeks. Catch per unit effort was greatest in the Ashburton
      Estuary in October, due to an influx of green sawfish Pristis zijsron pups, and
      was orders of magnitude higher than previously reported for any Pristidae; the
      study sites contained P. zijsron up to almost 3 m total length. This study
      identified the first pupping site for P. zijsron in Western Australia, and the
      most southerly known nursery area for the species in Australian waters, and is
      potentially the most important globally. 

PMID- 25943153
TI  - A phenomenology of occupation-based hand therapy.
AB  - BACKGROUND/AIM: The existing tension between holistic, occupation focused
      approaches and the medical model in occupational therapy is most evident in the
      area of hand therapy. Occupation-based hand therapy has been proposed as a means
      to alleviate this tension. However, there is a lack of research on occupation
      based hand therapy. Clearly describing and defining what constitutes occupation
      based hand therapy can facilitate efficacy research and help promote occupation
      based practice in keeping with the philosophy of the profession. METHODS: The
      qualitative approach of phenomenology as described by Moustakas was used.
      Participants who were occupational therapists with more than 5 years of
      experience who self -identified as occupation-based practitioners were recruited
      to the point of saturation using criterion and chain sampling for a final total
      of 10 participants. Data were collected through audio recorded telephone
      interviews and electronic mail. The data were reduced and distilled into a
      description of the experience of providing occupation-based hand therapy.
      RESULTS: Participants described the experience of providing occupation-based hand
      therapy around the concepts of influences, psychosocial benefits, procedural
      elements of practice and challenges. CONCLUSION: Findings of this study can
      assist occupational therapists to develop a more occupation-based intervention
      program through focusing on occupation-based theory, being intentional, using
      occupation-focused interventions and building an occupation focused context.
      Findings can also inform future research into the efficacy of occupation-based
      hand therapy, appropriate timing for balancing occupation with tissue protection,
      and the effects of therapist experience on their ability to use an occupation
      based approach in hand therapy.

PMID- 25943154
TI  - Challenges for Plasmodium vivax malaria elimination in the genomics era.

PMID- 25943155
TI  - Immature reticulocytes as preferential host cells and the challenges for in vitro
      culture of Plasmodium vivax.

PMID- 25943158
TI  - Robot-assisted radical cystectomy with intracorporeal urinary diversion: impact
      on an established enhanced recovery protocol.
AB  - OBJECTIVES: To assess the impact of the introduction of robot-assisted radical
      cystectomy (RARC) on an established enhanced recovery programme (ERP) and to
      examine the effect on mortality and morbidity rates, transfusion rates, and
      length of stay (LOS). PATIENTS AND METHODS: Data on 102 consecutive patients
      undergoing RARC with full intracorporeal reconstruction were obtained from our
      prospectively updated institutional database. These data were compared to
      previously published retrospective results from three separate groups of patients
      undergoing open radical cystectomy (ORC) at our centre. Our primary focus was
      perioperative outcomes including transfusion rate, complication rates, 30- and 90
      day mortality rates, and LOS. RESULTS: The demographics of the comparative groups
      showed no significant difference in age, gender distribution, and American
      Society of Anesthesiologists grade. A significant reduction in transfusion rate
      was seen in RARC vs ORC (P < 0.001). The median LOS for the RARC group was 8 vs
      13 days for the ORC group (P < 0.001). There was trend to a lower total
      complication rate (48% vs 31%). The 30- and 90-day mortality rates were
      equivalent between the groups (2%). CONCLUSIONS: Introduction of RARC and
      intracorporeal reconstruction represents the single biggest impact on our ERP,
      with significant reduction in transfusion rates and LOS, and a trend towards a
      lower complication rate.

PMID- 25943156
TI  - Origins and implications of neglect of G6PD deficiency and primaquine toxicity in
      Plasmodium vivax malaria.
AB  - Most of the tens of millions of clinical attacks caused by Plasmodium vivax each
      year likely originate from dormant liver forms called hypnozoites. We do not
      systematically attack that reservoir because the only drug available, primaquine,
      is poorly suited to doing so. Primaquine was licenced for anti-relapse therapy in
      1952 and became available despite threatening patients having an inborn
      deficiency of glucose-6-phosphate dehydrogenase (G6PD) with acute haemolytic
      anaemia. The standard method for screening G6PD deficiency, the fluorescent spot
      test, has proved impractical where most malaria patients live. The blind
      administration of daily primaquine is dangerous, but so too are the relapses
      invited by withholding treatment. Absent G6PD screening, providers must choose
      between risking harm by the parasite or its treatment. How did this dilemma
      escape redress in science, clinical medicine and public health? This review
      offers critical historic reflection on the neglect of this serious problem in the
      chemotherapy of P. vivax. 

PMID- 25943159
TI  - Design and Synthesis of Pyrimidine-Based Iridium(III) Complexes with Horizontal
      Orientation for Orange and White Phosphorescent OLEDs.
AB  - Two phosphorescent Ir(III) complexes Ir(ppm)2(acac) and Ir(dmppm)2(acac) were
      synthesized and characterized with emission ranged at 584/600 nm and high
      photoluminescence quantum yields (PLQYs) of 0.90/0.92, respectively. The angle
      dependent PL spectra analysis reveals that the two orange iridium(III) complexes
      embodied horizontal orientation property. The high photoluminescence quantum
      yield and high horizontal dipoles ratio determine their excellent device
      performance. The devices based on Ir(ppm)2(acac) and Ir(dmppm)2(acac) achieved
      efficiencies of 26.8% and 28.2%, respectively, which can be comparable to the
      best orange phosphorescent devices reported in the literature. Furthermore, with
      the introduction of FIrpic as sky-blue emitter, phosphorescent two-element white
      organic light-emitting devices (OLEDs) have been realized with external quantum
      efficiencies (EQEs) as high as 25%, which are the highest values among the
      reported two-element white OLEDs. 

PMID- 25943160
TI  - Multiple modes of iron uptake by the filamentous, siderophore-producing
      cyanobacterium, Anabaena sp. PCC 7120.
AB  - Iron is a member of a small group of nutrients that limits aquatic primary
      production. Mechanisms for utilizing iron have to be efficient and adapted
      according to the ecological niche. In respect to iron acquisition cyanobacteria,
      prokaryotic oxygen evolving photosynthetic organisms can be divided into
      siderophore- and non-siderophore-producing strains. The results presented in this
      paper suggest that the situation is far more complex. To understand the
      bioavailability of different iron substrates and the advantages of various uptake
      strategies, we examined iron uptake mechanisms in the siderophore-producing
      cyanobacterium Anabaena sp. PCC 7120. Comparison of the uptake of iron complexed
      with exogenous (desferrioxamine B, DFB) or to self-secreted (schizokinen)
      siderophores by Anabaena sp. revealed that uptake of the endogenous produced
      siderophore complexed to iron is more efficient. In addition, Anabaena sp. is
      able to take up dissolved, ferric iron hydroxide species (Fe') via a reductive
      mechanism. Thus, Anabaena sp. exhibits both, siderophore- and non-siderophore
      mediated iron uptake. While assimilation of Fe' and FeDFB are not induced by iron
      starvation, FeSchizokinen uptake rates increase with increasing iron starvation.
      Consequently, we suggest that Fe' reduction and uptake is advantageous for low
      density cultures, while at higher densities siderophore uptake is preferred. 

PMID- 25943157
TI  - Advances in genetics and genomics: use and limitations in achieving malaria
      elimination goals.
AB  - Success of the global research agenda towards eradication of malaria will depend
      on the development of new tools, including drugs, vaccines, insecticides and
      diagnostics. Genetic and genomic information now available for the malaria
      parasites, their mosquito vectors and human host, can be harnessed to both
      develop these tools and monitor their effectiveness. Here we review and provide
      specific examples of current technological advances and how these genetic and
      genomic tools have increased our knowledge of host, parasite and vector biology
      in relation to malaria elimination and in turn enhanced the potential to reach
      that goal. We then discuss limitations of these tools and future prospects for
      the successful achievement of global malaria elimination goals. 

PMID- 25943163
TI  - National tuberculosis prevalence surveys in Asia, 1990-2012: an overview of
      results and lessons learned.
AB  - OBJECTIVE AND METHODS: In many countries, national tuberculosis (TB) prevalence
      surveys are the only way to reliably measure the burden of TB disease and monitor
      trends. They can also provide evidence about the current performance of TB care
      and control and how this could be improved. We developed an inventory of Asian
      surveys from 1953 to 2012 and then compiled and analysed a standard set of data
      for all national surveys implemented between 1990 (the baseline year for 2015
      global TB targets) and 2012. RESULTS: There were 21 surveys in 12 countries
      between 1990 and 2012; published results were available for 18. The participation
      rate was at least 80% and often much higher except for two surveys in Thailand.
      The prevalence of bacteriologically-positive TB disease among adults aged >=15
      years varied widely among countries (1.2 per 1000 population in China in 2010 to
      15 per 1000 population in Cambodia in 2002), but age and sex distribution
      patterns were consistent with a progressive increase in rates of disease by age,
      and men accounting for 66-75% of prevalent cases. A high proportion of cases (40
      79% across all surveys) did not report TB symptoms that met screening criteria
      (generally cough of 2-3 weeks or more, and blood in the sputum) and were only
      detected due to chest X-ray screening of all survey participants; this proportion
      increased over time in countries with repeat survey data. The ratio of prevalent
      cases to cases notified to national TB programmes was typically around two, but
      was as high as three in Lao PDR and Pakistan even after the internationally
      recommended TB control strategy had been implemented nationwide for several
      years. Four countries (China, Cambodia, the Republic of Korea and the Philippines
      demonstrated declines in smear or culture-positive pulmonary TB prevalence of
      approximately 50% over 10 years. CONCLUSIONS: National TB prevalence surveys in
      Asia show that large reductions in the prevalence of TB disease can be achieved
      within a decade, that men bear much more of the burden than women and that the
      epidemic is ageing. Comparisons among countries show that more can be achieved in
      TB control in some countries with existing strategies and technologies. However,
      with many prevalent cases not reporting classic TB symptoms, all countries face
      the challenge of defining and implementing strategies that will result in earlier
      detection and treatment of cases.

PMID- 25943162
TI  - Ventricular rate during acute atrial fibrillation and outcome of electrical
      cardioversion: The FinCV Study.
AB  - INTRODUCTION: The impact of ventricular rate (VR) on the outcome of electrical
      cardioversion (ECV) of acute atrial fibrillation (AF) is currently unknown. We
      aimed to determine the effect of VR during acute AF on the success of ECV,
      recurrence of AF, and occurrence of post-cardioversion complications in 30 days
      of follow-up. METHODS: A total of 6,624 ECVs were performed in 2,821 consecutive
      patients with AF lasting < 48 hours. VR <= 60 bpm was defined low, and VR >= 160
      bpm high. RESULTS: The median VR before ECV was 109 bpm. The success rate of ECV
      was 94.2%. Bradycardia occurred in 62 (0.9%) and thromboembolic complications in
      39 (0.6%) ECVs. Low VR was observed before 75 (1.1%) ECVs, and male sex was its
      only independent predictor. High VR was observed in 165 (2.5%) ECVs. The
      independent predictors of high VR were younger age, < 12 h episode duration, no
      previous history of AF, and alcohol abuse. Low or high VR were not related to the
      success of ECV, incidence of thromboembolic or bradycardic complications, or
      recurrence of AF, although VR was significantly (P < 0.001) lower in the patients
      in whom AF recurred. CONCLUSION: VR during acute AF does not affect the efficacy
      or safety of ECV.

PMID- 25943165
TI  - Sex differences in the long-lasting consequences of adolescent ethanol exposure
      for the rewarding effects of cocaine in mice.
AB  - RATIONALE: The practice of binge drinking is very common among adolescents of
      both sexes. It can have long-term consequences with respect to drug consumption
      during adulthood, but knowledge on these effects in females is limited.
      OBJECTIVES: The long-lasting effects of intermittent exposure to ethanol (EtOH)
      during adolescence on different cocaine-elicited behaviours, including locomotor
      reactivity, conditioned place preference (CPP) and intravenous self
      administration, were evaluated in male and female adult mice. It was hypothesized
      that an EtOH binge during adolescence would increase sensitivity to the effects
      of a sub-threshold dose of cocaine and has a differential impact on the drug's
      effects in males and females. METHODS: Adolescent OF1 mice (postnatal day (PND)
      26) underwent a 2-week pre-treatment schedule consisting of 16 doses of EtOH (2.5
      g/kg) or saline (twice daily administrations separated by a 4-h interval i.p.)
      administered on two consecutive days separated by an interval of 2 days. Three
      weeks later (PND > 60), we assessed locomotor activity responses induced by an
      acute injection of different doses of cocaine in experiment 1 and the rewarding
      effects of cocaine on the CPP (1 mg/kg) and intravenous self-administration (1
      mg/kg/infusion) paradigms in experiment 2. RESULTS: Pre-exposure to EtOH during
      adolescence altered motor reactivity to cocaine in a dose- and sex-dependent
      manner, increased sensitivity to cocaine in CPP and enhanced self-administration
      in adult mice. CONCLUSIONS: The effects of intermittent exposure to ethanol
      during adolescence are evident in adulthood, during which greater sensitivity and
      intake of cocaine is observed and differ in each sex.

PMID- 25943166
TI  - Cannabidiol effects in the prepulse inhibition disruption induced by amphetamine.
AB  - RATIONALE: The information processing appears to be deficient in schizophrenia.
      Prepulse inhibition (PPI), which measures the inhibition of a motor response by a
      weak sensory event, is considered particularly useful to understand the biology
      of information processing in schizophrenia patients. Drugs that facilitate
      dopaminergic neurotransmission such as amphetamine induce PPI disruption in human
      and rodents. Clinical and neurobiological findings suggest that the
      endocannabinoid system and cannabinoids may be implicated in the pathophysiology
      and treatment of schizophrenia. Cannabidiol (CBD), a non-psychotomimetic
      constituent of the Cannabis sativa plant, has also been reported to have
      potential as an antipsychotic. OBJECTIVE: Our aim was to investigate if CBD
      pretreatment was able to prevent PPI disruption induced by amphetamine. Since one
      possible mechanism of CBD action is the facilitation of endocannabinoid-mediated
      neurotransmission through anandamide, we tested the effects of an anandamide
      hydrolysis inhibitor (URB597) in the amphetamine-induced PPI disruption. METHODS:
      Male Swiss mice were treated with CBD systemic or intra-accumbens, or URB597
      (systemic) prior to amphetamine and were exposed to PPI test. RESULTS:
      Amphetamine (10 mg/kg) disrupted PPI while CBD (15-60 mg/kg) or URB597 (0.1-1
      mg/kg) administered alone had no effect. Pretreatment with CBD attenuated the
      amphetamine-disruptive effects on PPI test after systemic or intra-accumbens
      administration. Similar effects were also found with the inhibitor of anandamide
      hydrolysis. CONCLUSION: These results corroborate findings indicating that CBD
      induces antipsychotic-like effects. In addition, they pointed to the nucleus
      accumbens as a possible site of these effects. The increase of anandamide
      availability may be enrolled in the CBD effects.

PMID- 25943167
TI  - PCP-based mice models of schizophrenia: differential behavioral, neurochemical
      and cellular effects of acute and subchronic treatments.
AB  - RATIONALE: N-methyl-D-aspartate receptor (NMDA-R) hypofunction has been proposed
      to account for the pathophysiology of schizophrenia. Thus, NMDA-R blockade has
      been used to model schizophrenia in experimental animals. Acute and repeated
      treatments have been successfully tested; however, long-term exposure to NMDA-R
      antagonists more likely resembles the core symptoms of the illness. OBJECTIVES:
      To explore whether schizophrenia-related behaviors are differentially induced by
      acute and subchronic phencyclidine (PCP) treatment in mice and to examine the
      neurobiological bases of these differences. RESULTS: Subchronic PCP induced a
      sensitization of acute locomotor effects. Spontaneous alternation in a T-maze and
      novel object recognition performance were impaired after subchronic but not acute
      PCP, suggesting a deficit in working memory. On the contrary, reversal learning
      and immobility in the tail suspension test were unaffected. Subchronic PCP
      significantly reduced basal dopamine but not serotonin output in medial
      prefrontal cortex (mPFC) and markedly decreased the expression of tyrosine
      hydroxylase in the ventral tegmental area. Finally, acute and subchronic PCP
      treatments evoked a different pattern of c-fos expression. At 1 h post-treatment,
      acute PCP increased c-fos expression in many cortical regions, striatum,
      thalamus, hippocampus, and dorsal raphe. However, the increased c-fos expression
      produced by subchronic PCP was restricted to the retrosplenial cortex, thalamus,
      hippocampus, and supramammillary nucleus. Four days after the last PCP injection,
      c-fos expression was still increased in the hippocampus of subchronic PCP-treated
      mice. CONCLUSIONS: Acute and subchronic PCP administration differently affects
      neuronal activity in brain regions relevant to schizophrenia, which could account
      for their different behavioral effects.

PMID- 25943168
TI  - Escalation of cocaine self-administration in adulthood after social defeat of
      adolescent rats: role of social experience and adaptive coping behavior.
AB  - BACKGROUND: The link between adolescent social stress and substance abuse is
      modeled in social defeat of adolescent male rats, at an age when social
      experiences are essential for neurobehavioral maturation. OBJECTIVE: We
      investigated the role of social experience and social defeat stress during
      adolescence on social behavior and cocaine self-administration (CocSelfAd) in
      early adulthood. METHODS: We manipulated social experience by housing male rats
      in pairs (PH) or singly (SH) on postnatal day (P) 21. In addition, rats were
      subjected to social defeat from P35-44. Social behavior was measured during the
      first and last social defeat in PH and SH adolescents and PH adults. After
      assessing the behavioral response to novelty and cocaine (P57-61), intrajugular
      catheters were implanted and CocSelfAd was analyzed. RESULTS: Residents were less
      aggressive toward PH adolescent intruders compared to PH adult intruders. Adults
      were submissive and defensive when attacked, whereas PH adolescents froze. In the
      course of repeated defeats, adolescent PH rats increased freezing, while SH rats
      decreased freezing. Longer attack-induced freezing after repeated defeats
      predicted escalated CocSelfAd in adulthood. PH controls acquired CocSelfAd more
      slowly than PH defeated and SH rats. Defeated PH rats increased CocSelfAd during
      progressive ratio schedules of reinforcement and during a 24-h continuous access
      binge compared to PH controls and SH defeated rats. CONCLUSIONS: Social defeat in
      adolescence of PH rats caused persistent increases in adult CocSelfAd. Adolescent
      PH rats coped with attacks adaptively by increasing freezing behavior after
      repeated social defeats, a measure that predicted CocSelfAd in adulthood.

PMID- 25943170
TI  - Quality of life changes in patients undergoing treatment for hepatocellular
      carcinoma.
AB  - PURPOSE: Hepatocellular carcinoma (HCC) is the second leading cause of cancer
      related death worldwide. One of the primary treatment goals for incurable
      advanced cases is to prolong quality of life (QoL). Thus, to determine which HCC
      therapies may be linked to a more favorable QoL, we assessed the association
      between QoL changes and different treatments in HCC patients. METHODS: We
      analyzed a non-randomized multicenter longitudinal study, which included 171
      patients treated with surgery (n = 53), ablation (n = 53) or embolization (n =
      65) from seven centers: four Asian and three European sites. All participants
      completed the EORTC QLQ-C30 and QLQ-HCC18 questionnaires before and after
      treatment. Propensity scores were calculated and used in addition to race for
      adjustment in the logistic regression model to account for the confounding
      effects of patient characteristics including age, gender, race, employment,
      living with family, at least one comorbid condition, years since diagnosis, prior
      treatment history, BCLC stage, Child-Pugh grade, cirrhosis, bilirubin levels and
      QoL score before treatment. RESULTS: After adjustment for confounders, patients
      tended to have higher odds of QoL deterioration when treated with ablation versus
      embolization (dyspnea: p = 0.019; appetite loss: p = 0.018; body image: p =
      0.035) or ablation versus surgery (dyspnea: p = 0.099; appetite loss: p = 0.100;
      body image: p = 0.038). CONCLUSIONS: There were significant differences in QoL
      deterioration across different treatment groups. This information may assist
      patients and providers when selecting patient-centered treatment approaches for
      HCC.

PMID- 25943169
TI  - Dissociation of mGlu2/3 agonist effects on ketamine-induced regional and event
      related oxygen signals.
AB  - RATIONALE: Validating preclinical biomarkers that predict treatment efficacy
      remains a critical imperative for neuropsychiatric drug discovery. With the
      establishment of novel in vivo imaging methods, it has become possible to think
      how such translational proof-of-concept studies may look. OBJECTIVES: The aim of
      this study was to use in vivo oxygen (O2) amperometry to simultaneously assess
      the regional and event/task-related O2 changes induced by ketamine challenge in
      rats, and to determine whether both of these signals are equivalently affected by
      the mGlu2/3 receptor agonist LY379268. METHODS: O2 signals were measured via
      carbon paste electrodes implanted in the anterior cingulate cortex (ACC) of rats
      trained to perform a simple reaction time task (SRT). SRT performance, event
      related ACC O2 responses, and regional ACC O2 signal were recorded simultaneously
      in animals treated with ketamine (10 mg/kg) and/or LY379268 (3 mg/kg). RESULTS: A
      consistent relationship was observed between baseline SRT performance and related
      ACC O2 signals, suggesting that ACC engagement is likely to be a requirement for
      optimal task performance. Ketamine induced a robust and consistent slowing in
      reaction times that was reflected by a delayed event-related ACC O2 signal
      increase compared to vehicle controls. Ketamine also produced a regional and task
      independent 60-min increase in ACC O2 levels which was effectively attenuated by
      LY379268. However, LY379238 failed to reverse alterations in event-related O2
      signals and associated SRT task performance. CONCLUSIONS: These findings raise
      questions about the degree to which such reversals of regional ketamine O2
      signals could potentially be claimed to predict drug treatment efficacy.

PMID- 25943171
TI  - Formation of Poly[d(A-T)2] Specific Z-DNA by a Cationic Porphyrin.
AB  - Typical CD spectrum of the right-handed poly[d(A-T)2] was reversed when trans
      bis(N-methylpyrimidium-4-yl)diphenyl porphyrin (trans-BMPyP) was bound,
      suggesting that the helicity of the polynucleotide was reversed to the left
      handed form. The formation of the left-handed Z-form poly[d(A-T)2] was confirmed
      by (31)P NMR, in which a single (31)P peak of B-form poly[d(A-T)2] was split into
      two peaks, which is similar to the conventional B-Z transition of poly[d(G-C)2]
      induced by the high ionic strength. The observed B-Z transition is unique for
      poly[d(A-T)2]. The other polynucleotides, including poly[d(G-C)2],
      poly(dG).poly(dC) and poly(dA).poly(dT) remained as the right-handed form in the
      presence of the same porphyrin. This observation suggests that the porphyrin
      array that was formed along the poly[d(A-T)2] provides a template to which left
      handed poly[d(A-T)2] is associated with an electrostatic interaction. 

PMID- 25943172
TI  - A comparative study of different concentrations of topical bevacizumab on the
      recurrence rate of excised primary pterygium: a short-term follow-up study.
AB  - The present study was undertaken to compare the pterygium recurrence rates after
      treatment with two different concentrations of topical bevacizumab in those who
      had undergone a primary pterygium excision. The 90 patients who underwent
      pterygium excision were enrolled in this prospective, placebo-controlled double
      blinded interventional case series. The participants were randomly categorized
      into 3 groups each consisting of 30 subjects. 24 h after surgery, Group II and
      Group III received a total of 5 and 10 mg/mL dose of topical bevacizumab,
      respectively; whereas patients in Group I were administered only a placebo
      starting a day after surgery. Participants were instructed to instill their
      topical medicines 4 times a day for 1 week. The patients were examined for
      pterygium recurrence and complications at postoperative 1, 7, and 14 days as well
      as each month during the following year. Pterygia recurred in 14 patients (46.7
      %) in Group I and in 4 patients (13.3 %) in Group II. No recurrence was observed
      in Group III during the follow-up period. The Kaplan-Meier survival analysis
      disclosed a significantly better outcome for those who had been treated with 10
      mg/mL concentrations of bevacizumab (Mantel-Cox log rank analysis, P < 0.001).
      The mean recurrence time was not significantly different between Group I and
      Group II. No ocular or systemic complication developed till the end of follow-up.
      Thus, 10 mg/mL concentration of topical bevacizumab was more efficacious than 5
      mg/mL dose in preventing pterygium recurrence.

PMID- 25943173
TI  - Changes in choroidal thickness after photodynamic therapy for Sturge-Weber
      syndrome.

PMID- 25943174
TI  - Selective laser trabeculoplasty (SLT): 1-year results in early and advanced open
      angle glaucoma.
AB  - The purpose of this study was to examine the efficacy of selective laser
      trabeculoplasty (SLT) in eyes with early and more advanced stages of open angle
      glaucoma within 1 year of follow-up. Retrospective chart review in a consecutive
      series of patients treated by SLT to reduce intraocular pressure (IOP) or
      decrease number of topical medications in cases of discomfort and allergy. The
      cup-to-disc ratio of the optic nerve and the GSS 2 (glaucoma staging system 2)
      was used to differentiate between early (group 1) and more advanced (group 2)
      stages of glaucoma. At the time of SLT treatment, no new signs of glaucoma
      progression were seen. Only the first treated eye of every patient was included
      in the analysis. In group 1 (early glaucoma), 27 eyes were included. IOP
      reduction <21 mmHg/>20 % of the preoperative IOP-value and reduction of
      medication were achieved in 17 eyes (62.96 %). Successful re-treatment was
      necessary in 2 eyes (7.4 %). In group 2 (advanced glaucoma), 44 eyes underwent
      SLT. In eight eyes (18.18 %), filtrating surgery was necessary after initial SLT.
      In the remaining 36 eyes, IOP reduction <21 mmHg/>20 % of the baseline IOP was
      achieved in 26 eyes (59.09 % of 44 eyes) and IOP reduction <18 mmHg/> 30 % of the
      baseline IOP in 22 eyes (50 % of 44 eyes). SLT was safe and effective in nearly
      2/3 of early glaucoma patients and also in 50 % of advanced glaucoma patients
      using stronger criteria of success. Failure of SLT in advanced glaucoma should
      lead to immediate filtrating surgery, which seems not to be associated with
      higher risk of fibrosis.

PMID- 25943175
TI  - Clinical relevance of genetic polymorphism in CYP2C9 gene to pharmacodynamics and
      pharmacokinetics of phenytoin in epileptic patients: validatory pharmacogenomic
      approach to pharmacovigilance.
AB  - AIMS AND OBJECTIVES: Variations in drug metabolizing genes are known to have a
      clinical impact on AED therapy. We genotyped normal and epileptic patient cohorts
      of monoethnic population of Kashmir valley for CYP2C9 gene and allelic
      polymorphism and investigated the effect of CYP2C9*2 and *3 polymorphism on the
      Pharmacokinetic and therapeutic and/or adverse pharmacodynamic responses to
      Phenytoin in the idiopathic epilepsy patients. METHODS: PCR-RFLP methods were
      used for genotyping of 121 normal controls and 92 idiopathic epilepsy patients
      for CYP2C9*2 and *3 polymorphism, the results were validated by direct
      sequencing. Phenytoin pharmacokinetic (PK) analysis in idiopathic epilepsy
      patients was done using a validated EMIT assay technique. Pharmacodynamic
      analysis was done by evaluating clinical response to phenytoin therapy and ADR
      monitoring. RESULTS: The respective frequencies of CYP2C9 *1, *2, and *3 alleles
      were 64%, 6.6%, 29.3%, and 58%, 9.8%, 32.6% in controls and idiopathic epilepsy
      patients from Kashmir valley. PK analysis revealed that AUC0a??4 was a better
      surrogate biomarker of CYP2C9 metabolizer status compared to C4 and C0
      concentrations alone. A comparison of a??phenytoin response categoriesa?? among
      CYP2C9 Wild and Heterozygous groups did not reveal any significant difference
      between the groups (p=0.3800). CONCLUSION: CYP2C9* 3 was the most frequent mutant
      allele found in healthy controls and idiopathic epilepsy patients of ethnic
      Kashmiri population. CYP2C9 genotype based phenytoin therapy is highly relevant
      in Kashmiri population due to a high incidence of genetic variations associated
      with therapeutic and adverse responses to phenytoin. Phenytoin AUC0a??4 tends to
      correlate better with genetic polymorphism of CYP2C9.

PMID- 25943176
TI  - Effect of mavoglurant (AFQ056), a selective mGluR5 antagonist, on the
      pharmacokinetics of a combined oral contraceptive containing ethinyl estradiol
      and levonorgestrel in healthy women.
AB  - OBJECTIVE: To compare the pharmacokinetics (PKs) of a combination oral
      contraceptive (OC) when given alone or concomitantly with the selective
      metabotropic glutamate receptor 5 antagonist mavoglurant (AFQ056). METHODS: This
      open-label, fixed-sequence, two-period study included 30 healthy female subjects
      aged 18-40 years. In period 1, a single oral dose of an OC containing 30 MUg
      ethinyl estradiol (EE)/150 MUg levonorgestrel (LNG) was administered alone. In
      period 2, the OC was administered with a clinically relevant multiple dose of
      mavoglurant 100 mg b.i.d. under steady-state conditions. Plasma concentrations of
      EE and LNG were measured up to 72 hours post administration, and the PK
      parameters Cmax and AUClast were estimated using noncompartmental methods.
      RESULTS: The geometric mean ratios of EE Cmax and AUClast obtained with and
      without mavoglurant were 0.97 (90% confidence interval (CI): 0.90-1.06) and 0.94
      (90% CI: 0.86-1.03), respectively. The corresponding Cmax and AUClast for LNG
      were 0.81 (90% CI: 0.75-0.87) and 0.68 (90% CI: 0.63-0.73), respectively.
      CONCLUSIONS: In conclusion, EE PK was unchanged, whereas Cmax and AUClast of LNG
      were 19% and 32% lower, respectively, when given with mavoglurant Further
      investigation regarding the impact on contraceptive efficacy is warranted.

PMID- 25943177
TI  - Acute alcohol intoxication in a child following ingestion of an ethyl-alcohol
      based hand sanitizer.
AB  - While uncommon, ingestion of ethanol-based hand sanitizers by children may be
      associated with significant intoxication. We report the case of a 7-year-old with
      acute alcohol intoxication following hand sanitizer ingestion. Alcohol
      elimination in this patient followed zero-order kinetics with a clearance rate of
      22.5 mg/kg/h, consistent with the limited pharmacokinetic information available
      for children who experience alcohol intoxication from more traditional sources. 

PMID- 25943178
TI  - A novel recurrent EP300-ZNF384 gene fusion in B-cell precursor acute
      lymphoblastic leukemia.

PMID- 25943179
TI  - High concordance of genomic and cytogenetic aberrations between peripheral blood
      and bone marrow in myelodysplastic syndrome (MDS).
AB  - Bone marrow (BM) genetic abnormalities in myelodysplastic syndrome (MDS) have
      provided important biological and prognostic information; however, frequent BM
      sampling in older patients has been associated with significant morbidity.
      Utilizing single-nucleotide polymorphism array (SNP-A) and targeted gene
      sequencing (TGS) of 24 frequently mutated genes in MDS, we assessed the
      concordance of genetic abnormalities in BM and peripheral blood (PB) samples
      concurrently from 201 MDS patients. SNP-A karyotype in BM was abnormal in 108
      (54%) and normal in 93 (46%) patients, with 95% (190/201) having an identical PB
      karyotype. The median copy number (CN) for deletions was significantly lower in
      BM (CN:1.4 (1-1.9)) than in PB (CN:1.5 (1-1.95), P<0.001). Using TGS, 71%
      (130/183) patients had BM somatic mutations with 95% (124/130) having identical
      mutations in PB. The mutant allele burden was lower in PB (median 27% (1-96%))
      compared with BM (median 29% (1-100%); P=0.14) with no significant difference in
      the number, types of mutations or World Health Organization subtype. In all
      patients with discordant SNP (n=11) and mutation (n=6) profiles between BM and
      PB, shared abnormalities were always present irrespective of treatment status.
      Overall, 86% of patients had a clonal aberration with 95% having identical SNP-A
      karyotype and mutations in PB, thus enabling frequent assessment of response to
      treatment and disease evolution especially in patients with fibrotic or
      hypocellular marrows. 

PMID- 25943182
TI  - Research on the health of people who experience detention or incarceration in
      Canada: a scoping review.
AB  - BACKGROUND: We conducted a scoping review to define the extent and type of
      quantitative health status research conducted from 1993 to 2014 with people who
      have experienced detention or incarceration in correctional facilities in Canada.
      METHODS: We searched 15 databases, reviewed reference lists and relevant
      websites, and consulted with key stakeholders to identify eligible studies. We
      reviewed records for eligibility and extracted relevant data from eligible
      articles. RESULTS: We identified 194 studies that were eligible for inclusion.
      Most studies were conducted with males and with persons in federal facilities,
      and focused on mental health, substance use, and social determinant of health
      outcomes. CONCLUSIONS: Health status data are limited for several outcomes, such
      as chronic disease, injury and sexual and reproductive health, and for persons in
      provincial facilities and post-release. Efforts should be made to improve data
      collection and knowledge dissemination, so that relevant data can be used more
      effectively to improve health and health care in this population.

PMID- 25943181
TI  - Effectiveness of azacitidine in unselected high-risk myelodysplastic syndromes:
      results from the Spanish registry.
AB  - The benefit of azacitidine treatment in survival of high-risk myelodysplastic
      syndromes (MDS) patients compared with conventional care treatment (CCT) has not
      been established outside clinical trials. To assess its effectiveness, we
      compared overall survival (OS) between azacitidine and conventional treatment
      (CCT) in high-risk MDS patients, excluding those undergoing stem cell
      transplantation, submitted to the Spanish MDS registry from 2000 to 2013. Several
      Cox regression and competing risk models, considering azacitidine as a time
      dependent covariate, were used to assess survival and acute myeloblastic leukemia
      (AML) progression. Among 821 patients included, 251 received azacitidine. Median
      survival was 13.4 (11.8-16) months for azacitidine-treated patients and 12.2 (11
      14.1) for patients under CCT (P=0.41). In a multivariate model, age,
      International prognostic scoring system and lactate dehydrogenase were predictors
      of OS whereas azacitidine was not (adjusted odds ratio 1.08, 95% confidence
      interval 0.86-1.35, P=0.49). However, in patients with chromosome 7
      abnormalities, a trend toward a better survival was observed in azacitidine
      treated patients (median survival 13.3 (11-18) months) compared with CCT (median
      survival 8.6 (5-10.4) months, P=0.08). In conclusion, our data show that, in
      spite of a widespread use of azacitidine, there is a lack of improvement in
      survival over the years. Identification of predicting factors of response and
      survival is mandatory. 

PMID- 25943180
TI  - The pre-B-cell receptor checkpoint in acute lymphoblastic leukaemia.
AB  - The B-cell receptor (BCR) and its immature form, the precursor-BCR (pre-BCR),
      have a central role in the control of B-cell development, which is dependent on a
      sequence of cell-fate decisions at specific antigen-independent checkpoints. Pre
      BCR expression provides the first checkpoint, which controls differentiation of
      pre-B to immature B-cells in normal haemopoiesis. Pre-BCR signalling regulates
      and co-ordinates diverse processes within the pre-B cell, including clonal
      selection, proliferation and subsequent maturation. In B-cell precursor acute
      lymphoblastic leukaemia (BCP-ALL), B-cell development is arrested at this
      checkpoint. Moreover, malignant blasts avoid clonal extinction by hijacking pre
      BCR signalling in favour of the development of BCP-ALL. Here, we discuss three
      mechanisms that occur in different subtypes of BCP-ALL: (i) blocking pre-BCR
      expression; (ii) activating pre-BCR-mediated pro-survival and pro-proliferative
      signalling, while inhibiting cell cycle arrest and maturation; and (iii)
      bypassing the pre-BCR checkpoint and activating pro-survival signalling through
      pre-BCR independent alternative mechanisms. A complete understanding of the BCP
      ALL-specific signalling networks will highlight their application in BCP-ALL
      therapy. 

PMID- 25943183
TI  - Preoperative and postoperative analgesic techniques in the treatment of patients
      undergoing transabdominal hysterectomy: a preliminary randomized trial.
AB  - BACKGROUND: Although pre-emptive analgesia is commonly used for the management of
      postoperative pain in developed countries, no defined protocol has been carried
      out and widely practiced, especially in transabdominal hysterectomy. Keeping this
      in mind the present study aimed to investigate the effects of multimodal pre
      emptive analgesia on pain management, stress response and inflammatory factors of
      patients undergoing transabdominal hysterectomy to find an optimized way of pre
      emptive analgesia. METHODS: One hundred patients undergoing abdominal
      hysterectomy were randomly divided into four groups (Trial registration: ChiCTR
      IPR-15005848). Group P1 was given intravenous flurbiprofen and epidural fentanyl
      + ketamine before surgery; Group P2 received intravenous flurbiprofen before
      surgery and epidural fentanyl + ketamine after surgery; Group P3 was given
      epidural fentanyl + ketamine before surgery and intravenous flurbiprofen after
      surgery; Patients in Group C received normal saline treatment. RESULTS: Compared
      with control group, the first time to request additional analgesics after surgery
      were significantly later (P < 0.05), 24 h dosage of analgesia were significantly
      less (P < 0.05), VAS score at all time periods after surgery were significantly
      lower (P < 0.05) in Group P1, P2, or P3. At 12 h or 24 h after surgery, VAS score
      in Group P1 was significantly lower than that in group P2 or P3 (P < 0.05, P <
      0.05). No significant adverse effects were found among the groups (P > 0.05). At
      1 or 2 days after surgery, the levels of cortisol, glucose, and IL-6, TNF-alpha
      in group P1, P2, and P3 were significantly lower than those in group C (P <
      0.05); while, the levels in group P2, P3 were significantly lower than those in
      group P1 (P < 0.05). CONCLUSION: Multimodal pre-emptive analgesia could
      significantly lower VAS score, inhibit stress response, and reduce inflammatory
      response in patients undergoing transabdominal hysterectomy, which can be a
      rational strategy for pain control in future. TRIAL REGISTRATION: ChiCTR-IPR
      15005848 on January 17, 2015.

PMID- 25943185
TI  - The reduction of surface plasmon losses in quasi-suspended graphene.
AB  - Highly confined surface plasmons on graphene attract substantial interest as
      potential information carriers for highly integrated photonic data processing
      circuits. However, plasmon losses remain the main obstacle for implementation of
      such devices. In near-field microscopic experiments performed at the wavelength
      of 10 MUm we show that a substantial reduction of plasmon damping can be achieved
      by placing a nanometric polymer nano-dots spacer between the graphene layer and
      the supporting silicon oxide slab making graphene quasi-suspended. We argue that
      reduction of plasmon losses is attributed to weaker coupling with substrate
      phonons in the quasi-suspended graphene. 

PMID- 25943184
TI  - Involvement of PI3K/Akt Signaling Pathway and Its Downstream Intracellular
      Targets in the Antidepressant-Like Effect of Creatine.
AB  - Creatine has been proposed to exert beneficial effects in the management of
      depression, but the cell signaling pathways implicated in its antidepressant
      effects are not well established. This study investigated the involvement of
      PI3K/Akt signaling pathway and its downstream intracellular targets in the
      antidepressant-like effect of creatine. The acute treatment of mice with creatine
      (1 mg/kg, po) increased the Akt and P70S6K phosphorylation, and HO-1, GPx and
      PSD95 immunocontents. The pretreatment of mice with LY294002 (10 nmol/mouse, icv,
      PI3K inhibitor), wortmannin (0.1 MUg/mouse, icv, PI3K inhibitor), ZnPP (10
      MUg/mouse, icv, HO-1 inhibitor), or rapamycin (0.2 nmol/mouse, icv, mTOR
      inhibitor) prevented the antidepressant-like effect of creatine (1 mg/kg, po) in
      the TST. In addition, the administration of subeffective dose of either the
      selective GSK3 inhibitor AR-A014418 (0.01 MUg/mouse, icv), the nonselective GSK3
      inhibitor lithium chloride (10 mg/kg, po), or the HO-1 inductor CoPP (0.01
      MUg/mouse, icv), in combination with a subeffective dose of creatine (0.01 mg/kg,
      po) reduced the immobility time in the TST as compared with either drug alone. No
      treatment caused significant changes in the locomotor activity of mice. These
      results indicate that the antidepressant-like effect of creatine in the TST
      depends on the activation of Akt, Nrf2/HO-1, GPx, and mTOR, and GSK3 inhibition.

PMID- 25943186
TI  - Bilateral occipito-condylar hyperplasia: a very rare anomaly treated with
      endoscopic endo-nasal approach.
AB  - INTRODUCTION: Occipito-condylar hyperplasia is a very rare anomaly of the cranio
      vertebral junction that was only reported in two patients before and managed
      through posterior approach. CASE MATERIAL: A 10-year-old girl with a sudden
      attack of quadriparesis and respiratory distress was admitted to our center. A
      detailed work up favored a high cervical myelopathy due to bilateral occipito
      condylar hyperplasia and Chiari malformation. RESULTS: An endoscopic endo-nasal
      approach under navigation guide was used to drill the compressive lesion.
      CONCLUSION: Our patient is added to the literature as the third one that was
      approached through a different surgical corridor. Successful decompression with
      excellent results was gained.

PMID- 25943188
TI  - Anesthesia and organic aciduria: is the use of lactated Ringer's solution
      absolutely contraindicated?
AB  - BACKGROUND: Organic acidurias (OAs) are rare inborn errors of metabolism that can
      present with various neurologic manifestations, propensity for acute metabolic
      decompensation with anion-gap metabolic acidosis, developmental delay, poor
      feeding, and failure to thrive. OBJECTIVE: In this case series, we outline the
      anesthetic management and perioperative outcomes of OA patients. METHODS: We
      reviewed demographic characteristics, comorbidities, and perioperative course of
      patients with four different OAs who underwent anesthetic care at our institution
      between January 1, 2000, and December 31, 2013. RESULTS: Eleven patients with OA
      underwent 19 anesthetic procedures, of which 13 were <2 h in duration and seven
      were outpatient procedures. One patient with methylmalonic acidemia developed
      metabolic acidosis during a 10-h procedure with substantial blood loss but lacked
      evidence that this acidosis could be attributed to his underlying metabolic
      disease. The patients who received hydration with lactated Ringer's solution
      and/or nitrous oxide anesthetic had a perioperative course free of metabolic
      complication. Two patients died within 30 days of surgery from causes likely to
      be unrelated to anesthetic exposure. CONCLUSIONS: Our patients with various forms
      of metabolically compensated OAs tolerated anesthetics for surgical procedures
      without metabolic decompensation, even when lactated Ringer's solution was used
      for hydration. Measures to prevent protein catabolism and intraoperative events
      that may precipitate metabolic acidosis, in addition to close monitoring of acid
      base status during more extensive procedures, must be part of perioperative
      treatment of these patients.

PMID- 25943189
TI  - Erratum to: Comparison of tocilizumab as monotherapy or with add-on disease
      modifying antirheumatic drugs in patients with rheumatoid arthritis and
      inadequate responses to previous treatments: an open-label study close to
      clinical practice.

PMID- 25943187
TI  - A Comprehensive Review of Drug-Drug Interactions with Metformin.
AB  - Metformin is the world's most commonly used oral glucose-lowering drug for type 2
      diabetes, and this is mainly because it protects against diabetes-related
      mortality and all-cause mortality. Although it is an old drug, its mechanism of
      action has not yet been clarified and its pharmacokinetic pathway is still not
      fully understood. There is considerable inter-individual variability in the
      response to metformin, and this has led to many drug-drug interaction (DDI)
      studies of metformin. In this review, we describe both in vitro and human
      interaction studies of metformin both as a victim and as a perpetrator. We also
      clarify the importance of including pharmacodynamic end points in DDI studies of
      metformin and taking pharmacogenetic variation into account when performing these
      studies to avoid hidden pitfalls in the interpretation of DDIs with metformin.
      This evaluation of the literature has revealed holes in our knowledge and given
      clues as to where future DDI studies should be focused and performed. 

PMID- 25943192
TI  - Advantage of specialism: reproductive output is related to prey choice in a small
      raptor.
AB  - Predatory species' usage of different prey types is affected by both prey
      availability and selectivity. The diet during the breeding season may affect the
      reproductive success of individual pairs. We studied the prey use of a small
      reversed size-dimorphic raptor, the Eurasian sparrowhawk Accipiter nisus, with
      respect to prey weight on two organizational levels. Using 13 years of data from
      southern Norway, we related reproductive output of individual breeding events to
      prey size taken. Further, we assessed the regional variation in prey usage
      between five Fennoscandian populations. This was done by fitting optimum-type
      functions to the prey species' numbers or relative predation risks. Pairs that
      successfully completed the season with more fledglings displayed less variation
      in prey size, suggesting a possible adaptive benefit of diet specialism, or
      possibly a correlative effect due to higher prey availability or lower female
      hunting effort. This finding contrasts with earlier raptor studies, which have
      suggested benefits of dietary (and hence nutritional) diversity. Indeed, our
      results might be limited to nutritionally substitutable prey items. We also found
      a tendency suggesting that older females raised more fledglings than 1-year-old
      females. In the population-level analysis, we found that optimum-type functions
      with constant width and spatially variable average best described the
      relationship between relative predation risk and log weight. This can reflect
      local conditions, such as prey availability. Our findings and new methodological
      tools could apply to a broader spectrum of predators. They also highlight the
      role of viewing usage or choice of prey at several spatial scales.

PMID- 25943190
TI  - Decreased expression of the NF-kappaB family member RelB in lung fibroblasts from
      Smokers with and without COPD potentiates cigarette smoke-induced COX-2
      expression.
AB  - BACKGROUND: Heightened inflammation, including expression of COX-2, is associated
      with COPD pathogenesis. RelB is an NF-kappaB family member that attenuates COX-2
      in response to cigarette smoke by a mechanism that may involve the miRNA miR
      146a. There is no information on the expression of RelB in COPD or if RelB
      prevents COX-2 expression through miR-146a. METHODS: RelB, Cox-2 and miR-146a
      levels were evaluated in lung fibroblasts and blood samples derived from non
      smokers (Normal) and smokers (At Risk) with and without COPD by qRT-PCR. RelB and
      COX-2 protein levels were evaluated by western blot. Human lung fibroblasts from
      Normal subjects and smokers with and without COPD, along with RelB knock-down
      (siRNA) in Normal cells, were exposed to cigarette smoke extract (CSE) in vitro
      and COX-2 mRNA/protein and miR-146a levels assessed. RESULTS: Basal expression of
      RelB mRNA and protein were significantly lower in lung cells derived from smokers
      with and without COPD, the latter of which expressed more Cox-2 mRNA and protein
      in response to CSE. Knock-down of RelB in Normal fibroblasts increased Cox-2 mRNA
      and protein induction by CSE. Basal miR-146a levels were not different between
      the three groups, and only Normal fibroblasts increased miR-146a expression in
      response to smoke. There was a positive correlation between systemic RelB and Cox
      2 mRNA levels and circulating miR-146a levels were higher only in GOLD stage I
      subjects. CONCLUSIONS: Our data indicate that RelB attenuates COX-2 expression in
      lung structural cells, such that loss of pulmonary RelB may be an important
      determinant in the aberrant, heightened inflammation associated with COPD
      pathogenesis.

PMID- 25943191
TI  - Prognostic model for long-term survival of locally advanced non-small-cell lung
      cancer patients after neoadjuvant radiochemotherapy and resection integrating
      clinical and histopathologic factors.
AB  - BACKGROUND: Outcome of consecutive patients with locally advanced non-small cell
      lung cancer and histopathologically proven mediastional lymph node metastases
      treated with induction chemotherapy, neoadjuvant radiochemotherapy and
      thoracotomy at the West German Cancer Center between 08/2000 and 06/2012 was
      analysed. A clinico-pathological prognostic model for survival was built
      including partial or complete response according to computed tomography imaging
      (CT) as clinical parameters as well as pathologic complete remission (pCR) and
      mediastinal nodal clearance (MNC) as histopathologic factors. METHODS:
      Proportional hazard analysis (PHA) and recursive partitioning analysis (RPA) were
      used to identify prognostic factors for survival. Long-term survival was defined
      as survival >= 36 months. RESULTS: A total of 157 patients were treated, median
      follow-up was 97 months. Among these patients, pCR and MNC were observed in 41
      and 85 patients, respectively. Overall survival was 56 +/- 4% and 36 +/- 4% at 24
      and 60 months, respectively. Sensitivities of pCR and MNC to detect long-term
      survivors were 38% and 61%, specificities were 84% and 52%, respectively.
      Multivariable survival analysis revealed pCR, cN3 category, and gender, as
      prognostic factors at a level of alpha < 0.05. Considering only preoperative
      available parameters, CT response became significant. Classifying patients with a
      predicted hazard above the median as high risk group and the remaining as low
      risk patients yielded better separation of the survival curves by the inclusion
      of histopathologic factors than by preoperative factors alone (p < 0.0001, log
      rank test). Using RPA, pCR was identified as the top prognostic factor above
      clinical factors (p = 0.0006). No long term survivors were observed in patients
      with cT3-4 cN3 tumors without pCR. CONCLUSIONS: pCR is the dominant
      histopathologic response parameter and improves prognostic classifiers, based on
      clinical parameters. The validated prognostic model can be used to estimate
      individual prognosis and forms a basis for patient selection for treatment
      intensification.

PMID- 25943193
TI  - Habitat selection of a parasitoid mediated by volatiles informing on host and
      intraguild predator densities.
AB  - To locate and evaluate host patches before oviposition, parasitoids of
      herbivorous insects utilize plant volatiles and host-derived cues, but also
      evaluate predator-derived infochemicals to reduce predation risks. When foraging
      in host habitats infested with entomopathogenic fungi that can infect both a
      parasitoid and its host, parasitoids may reduce the risk of intraguild predation
      (IGP) by avoiding such patches. In this study, we examined whether the presence
      of the entomopathogenic fungi Metarhizium brunneum and Beauveria bassiana in soil
      habitats of a root herbivore, Delia radicum, affects the behavior of
      Trybliographa rapae, a parasitoid of D. radicum. Olfactometer bioassays revealed
      that T. rapae avoided fungal infested host habitats and that this was dependent
      on fungal species and density. In particular, the parasitoid avoided habitats
      with high densities of the more virulent fungus, M. brunneum. In addition, host
      density was found to be important for the attraction of T. rapae. Volatiles
      collected from host habitats revealed different compound profiles depending on
      fungal presence and density, which could explain the behavior of T. rapae. We
      conclude that T. rapae females may use volatile compounds to locate high
      densities of prey, but also compounds related to fungal presence to reduce the
      risk of IGP towards themselves and their offspring.

PMID- 25943195
TI  - Biochemical composition of the saliva and dental biofilm of children with Down
      syndrome.
AB  - BACKGROUND: The biochemical composition of the saliva and biofilm of children
      with Down syndrome (DS) may be associated with the incidence of caries in this
      population. AIM: To evaluate the biochemical composition of the saliva and dental
      biofilm of children with DS in the city of Porto Alegre, RS. DESIGN: The sample
      comprised 144 children between 6 and 14 years of age, of whom 61 had DS and 83
      did not. Stimulated saliva samples were collected from all participants, as were
      samples of 48-h biofilm. Fluoride (F), calcium (Ca), and phosphorus (Pi )
      concentrations in saliva and biofilm were determined by colorimetric method (Ca
      and Pi ) or selective electrode (F). The level of insoluble extracellular
      polysaccharide (EPS) in dental biofilm was measured using sulphuric acid method.
      RESULTS: Salivary concentration of F, Ca, and Pi did not differ between children
      with and without DS. The dental biofilm of children with DS, however, showed
      higher Pi and EPS levels than that of children without the syndrome (P < 0.05).
      CONCLUSIONS: The present results suggest that despite the salivary composition
      being similar between groups, the dental biofilm of children with DS has higher
      cariogenic potential than that of children without this condition.

PMID- 25943194
TI  - A novel large deletion of the ICR1 region including H19 and putative enhancer
      elements.
AB  - BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is a rare pediatric overgrowth
      disorder with a variable clinical phenotype caused by deregulation affecting
      imprinted genes in the chromosomal region 11p15. Alterations of the imprinting
      control region 1 (ICR1) at the IGF2/H19 locus resulting in biallelic expression
      of IGF2 and biallelic silencing of H19 account for approximately 10% of patients
      with BWS. The majority of these patients have epimutations of the ICR1 without
      detectable DNA sequence changes. Only a few patients were found to have
      deletions. Most of these deletions are small affecting different parts of the
      ICR1 differentially methylated region (ICR1-DMR) removing target sequences for
      CTCF. Only a very few deletions reported so far include the H19 gene in addition
      to the CTCF binding sites. None of these deletions include IGF2. CASE
      PRESENTATION: A male patient was born with hypotonia, facial dysmorphisms and
      hypoglycemia suggestive of Beckwith-Wiedemann syndrome. Using methylation
      specific (MS)-MLPA (Multiplex ligation-dependent probe amplification) we have
      identified a maternally inherited large deletion of the ICR1 region in a patient
      and his mother. The deletion results in a variable clinical expression with a
      classical BWS in the mother and a more severe presentation of BWS in her son. By
      genome-wide SNP array analysis the deletion was found to span ~100 kb genomic DNA
      including the ICR1DMR, H19, two adjacent non-imprinted genes and two of three
      predicted enhancer elements downstream to H19. Methylation analysis by deep
      bisulfite next generation sequencing revealed hypermethylation of the maternal
      allele at the IGF2 locus in both, mother and child, although IGF2 is not affected
      by the deletion. CONCLUSIONS: We here report on a novel large familial deletion
      of the ICR1 region in a BWS family. Due to the deletion of the ICR1-DMR CTCF
      binding cannot take place and the residual enhancer elements have access to the
      IGF2 promoters. The aberrant methylation (hypermethylation) of the maternal IGF2
      allele in both affected family members may reflect the active state of the
      normally silenced maternal IGF2 copy and can be a consequence of the deletion.
      The deletion results in a variable clinical phenotype and expression.

PMID- 25943196
TI  - Restitution and genetic differentiation of salmon populations in the southern
      Baltic genotyped with the Atlantic salmon 7K SNP array.
AB  - BACKGROUND: Native populations of Atlantic salmon in Poland, from the southern
      Baltic region, became extinct in the 1980s. Attempts to restitute salmon
      populations in Poland have been based on a Latvian salmon population from the
      Daugava river. Releases of hatchery reared smolts started in 1986, but to date,
      only one population with confirmed natural reproduction has been observed in the
      Slupia river. Our aim was to investigate the genetic differentiation of salmon
      populations in the southern Baltic using a 7K SNP (single nucleotide
      polymorphism) array in order to assess the impact of salmon restitution in
      Poland. METHODS: One hundred and forty salmon samples were collected from: the
      Polish Slupia river including wild salmon and individuals from two hatcheries,
      the Swedish Morrum river and the Lithuanian Neman river. All samples were
      genotyped using an Atlantic salmon 7K SNP array. A set of 3218 diagnostic SNPs
      was used for genetic analyses. RESULTS: Genetic structure analyses indicated that
      the individuals from the investigated populations were clustered into three
      groups i.e. one clade that included individuals from both hatcheries and the wild
      population from the Polish Slupia river, which was clearly separated from the
      other clades. An assignment test showed that there were no stray fish from the
      Morrum or Neman rivers in the sample analyzed from the Slupia river. Global FST
      over polymorphic loci was high (0.177). A strong genetic differentiation was
      observed between the Lithuanian and Swedish populations (FST = 0.28).
      CONCLUSIONS: Wild juvenile salmon specimens that were sampled from the Slupia
      river were the progeny of fish released from hatcheries and, most likely, were
      not progeny of stray fish from Sweden or Lithuania. Strong genetic differences
      were observed between the salmon populations from the three studied locations.
      Our recommendation is that future stocking activities that aim at restituting
      salmon populations in Poland include stocking material from the Lithuanian Neman
      river because of its closer geographic proximity.

PMID- 25943197
TI  - Genomic characterization of mutant laboratory mouse strains by exome sequencing
      and annotation lift-over.
AB  - BACKGROUND: Exome sequencing has become a popular method to evaluate undirected
      mutagenesis experiments in mice. However, the most suitable mouse strain for the
      biological model may be relatively distant from the standard mouse reference
      genome. For pinpointing causative variants, a matching reference with gene
      annotations is essential, but not always readily available. RESULTS: We present
      an approach that allows to use murine Ensembl annotations on alternative mouse
      strain assemblies. We resolved ENU-induced mutation screening for 8 phenotypic
      mutant lines generated on C3HeB/FeJ background aligning the sequences against the
      closely related, but not annotated reference of C3H/HeJ. Variants occurring in
      all strains were filtered out as specific for the C3HeB/FeJ strain but unrelated
      to mutagenesis. Variants occurring exclusively in all individuals of one mutant
      line and matching the inheritance model were selected as mutagenesis-related.
      These variants were annotated with gene and exon names lifted over from the
      standard murine reference mm9 to C3H/HeJ using megablast. For each mutant line,
      we could restrict the results to exonic variants in between 1 and 23 genes.
      CONCLUSIONS: The presented method of exonic annotation lift-over proved to be a
      valuable tool in the search for mutagenesis-derived coding genomic variants and
      the assessment of genotype-phenotype relationships.

PMID- 25943198
TI  - Type 3 endoleak following endovascular abdominal aortic aneurysm repair.

PMID- 25943199
TI  - Interferon alpha/beta Receptor-Deficient Mice as a Model for Ebola Virus Disease.
AB  - A major obstacle in ebolavirus research is the lack of a small-animal model for
      Sudan virus (SUDV), as well as other wild-type (WT) ebolaviruses. Here, we expand
      on research by Bray and by Lever et al suggesting that WT ebolaviruses are
      pathogenic in mice deficient for the type 1 interferon (IFN) alpha/beta receptor
      (IFNalpha/betaR-/-). We examined the disease course of several WT ebolaviruses:
      Boneface (SUDV/Bon) and Gulu variants of SUDV, Ebola virus (EBOV), Bundibugyo
      virus (BDBV), Tai Forest virus, and Reston virus (RESTV). We determined that
      exposure to WT SUDV or EBOV results in reproducible signs of disease in
      IFNalpha/betaR-/- mice, as measured by weight loss and partial lethality.
      Vaccination with the SUDV or EBOV glycoprotein (GP)-expressing Venezuelan equine
      encephalitis viral replicon particle vaccine protected these mice from SUDV/Bon
      and EBOV challenge, respectively. Treatment with SUDV- or EBOV-specific anti-GP
      antibodies protected mice from challenge when delivered 1-3 days after infection.
      Serial sampling experiments revealed evidence of disseminated intravascular
      coagulation in the livers of mice infected with the Boneface variant of SUDV,
      EBOV, and BDBV. Taken together, these data solidify the IFNalpha/betaR-/- mouse
      as an important and useful model for the study of WT EBOV disease. 

PMID- 25943200
TI  - Emergence of Multidrug-Resistant Influenza A(H1N1)pdm09 Virus Variants in an
      Immunocompromised Child Treated With Oseltamivir and Zanamivir.
AB  - Prolonged treatment of an immunocompromised child with oseltamivir and zanamivir
      for A(H1N1)pdm09 virus infection led to the emergence of viruses carrying H275Y
      and/or E119G in the neuraminidase (NA). When phenotypically evaluated by NA
      inhibition, the dual H275Y-E119G substitution caused highly reduced inhibition by
      4 NA inhibitors: oseltamivir, zanamivir, peramivir, and laninamivir. 

PMID- 25943201
TI  - Herpes Simplex [corrected] Virus Type 2 Shedding From Male Circumcision Wounds in
      Rakai, Uganda.
AB  - A prospective observational study of 176 men coinfected with human
      immunodeficiency virus and herpes simplex virus type 2 (HSV-2) was conducted to
      assess whether their sexual partners may be at an increased risk of HSV-2 from
      male circumcision (MC) wounds. Preoperative and weekly penile lavage samples were
      tested for penile HSV-2 shedding. Prevalence risk ratios (PRRs) were estimated
      using Poisson regression. Detectable penile HSV-2 shedding was present in 9.7% of
      men (17 of 176) before MC, compared with 12.9% (22 of 170) at 1 week (PRR, 1.33;
      95% confidence interval [CI], .74-2.38) and 14.8% (23 of 155) at 2 weeks (PRR,
      1.50; 95% CI, .86-2.62) after MC. HSV-2 shedding was lower among men with healed
      MC wounds (adjusted PRR, 0.62; 95% CI, .35-1.08). Men undergoing MC should be
      counseled on sexual abstinence and condom use. 

PMID- 25943202
TI  - Macrophage Migration Inhibitory Factor Is Detrimental in Pneumococcal Pneumonia
      and a Target for Therapeutic Immunomodulation.
AB  - Mortality from pneumococcal pneumonia remains high despite antibiotic therapy,
      highlighting the pathogenic potential for host inflammation. We demonstrate that
      macrophage migration inhibitory factor (MIF), an innate immune mediator, is
      detrimental for survival and associated with lung pathology, inflammatory
      cellular infiltration, and bacterial replication in a mouse model of pneumococcal
      pneumonia, despite being necessary for clearance from the nasopharynx. Treatment
      of animals with a small-molecule inhibitor of MIF improves survival by reducing
      inflammation and improving bacterial control. Our work demonstrates that MIF
      modulates beneficial versus detrimental inflammatory responses in the host
      pneumococcal interaction and is a potential target for therapeutic modulation. 

PMID- 25943204
TI  - Viral Interference: The Case of Influenza Viruses.

PMID- 25943203
TI  - CD8+ T-cell Responses in Flavivirus-Naive Individuals Following Immunization with
      a Live-Attenuated Tetravalent Dengue Vaccine Candidate.
AB  - We are developing a live-attenuated tetravalent dengue vaccine (TDV) candidate
      based on an attenuated dengue 2 virus (TDV-2) and 3 chimeric viruses containing
      the premembrane and envelope genes of dengue viruses (DENVs) -1, -3, and -4
      expressed in the context of the attenuated TDV-2 genome (TDV-1, TDV-3, and TDV-4,
      respectively). In this study, we analyzed and characterized the CD8(+) T-cell
      response in flavivirus-naive human volunteers vaccinated with 2 doses of TDV 90
      days apart via the subcutaneous or intradermal routes. Using peptide arrays and
      intracellular cytokine staining, we demonstrated that TDV elicits CD8(+) T cells
      targeting the nonstructural NS1, NS3, and NS5 proteins of TDV-2. The cells were
      characterized by the production of interferon-gamma, tumor necrosis factor-alpha,
      and to a lesser extent interleukin-2. Responses were highest on day 90 after the
      first dose and were still detectable on 180 days after the second dose. In
      addition, CD8(+) T cells were multifunctional, producing >=2 cytokines
      simultaneously, and cross-reactive to NS proteins of the other 3 DENV serotypes.
      Overall, these findings describe the capacity of our candidate dengue vaccine to
      elicit cellular immune responses and support the further evaluation of T-cell
      responses in samples from future TDV clinical trials. 

PMID- 25943205
TI  - What Is the Added Benefit of Oropharyngeal Swabs Compared to Nasal Swabs Alone
      for Respiratory Virus Detection in Hospitalized Children Aged <10 Years?
AB  - We evaluated the added value of collecting both nasal and oropharyngeal swabs,
      compared with collection of nasal swabs alone, for detection of common
      respiratory viruses by reverse transcription-polymerase chain reaction in
      hospitalized children aged <10 years. Nasal swabs had equal or greater
      sensitivity than oropharyngeal swabs for detection of respiratory syncytial
      virus, adenovirus, human metapneumovirus, rhinovirus, and influenza virus but not
      parainfluenza virus. The addition of an oropharyngeal swab, compared with use of
      a nasal swab alone, increased the frequency of detection of each respiratory
      virus by no more than 10% in children aged <10 years. 

PMID- 25943206
TI  - Interval Between Infections and Viral Hierarchy Are Determinants of Viral
      Interference Following Influenza Virus Infection in a Ferret Model.
AB  - BACKGROUND: Epidemiological studies suggest that, following infection with
      influenza virus, there is a short period during which a host experiences a lower
      susceptibility to infection with other influenza viruses. This viral interference
      appears to be independent of any antigenic similarities between the viruses. We
      used the ferret model of human influenza to systematically investigate viral
      interference. METHODS: Ferrets were first infected then challenged 1-14 days
      later with pairs of influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B
      viruses circulating in 2009 and 2010. RESULTS: Viral interference was observed
      when the interval between initiation of primary infection and subsequent
      challenge was <1 week. This effect was virus specific and occurred between
      antigenically related and unrelated viruses. Coinfections occurred when 1 or 3
      days separated infections. Ongoing shedding from the primary virus infection was
      associated with viral interference after the secondary challenge. CONCLUSIONS:
      The interval between infections and the sequential combination of viruses were
      important determinants of viral interference. The influenza viruses in this study
      appear to have an ordered hierarchy according to their ability to block or delay
      infection, which may contribute to the dominance of different viruses often seen
      in an influenza season.

PMID- 25943207
TI  - Effect of High Hydrostatic Pressure Combined with Moderate Heat to Inactivate
      Pressure-Resistant Bacteria in Water-Boiled Salted Duck.
AB  - The objective of this work was to study the effect of high hydrostatic pressure
      combined with moderate heat to inactivate pressure-resistant bacteria in water
      boiled salted duck meat (WBSDM), and to establish suitable procedures to improve
      the quality of WBSDM. The conditions (300 MPa/60  degrees C, 400 MPa/60  degrees
      C, and 500 MPa/50  degrees C) effectively inactivated the pressure-resistant
      bacteria (Bacillus cereus and Staphylococcus warneri) in WBSDM. Although more
      pressure-resistant than S. warneri, the above treatment conditions inactivated B.
      cereus more than 10(7) CFU/mL in buffer, and more than 10(6) CFU/g in WBSDM, and
      did not cause any changes in color, texture, or moisture content of products. The
      interaction between pressure and temperature is a more significant factor than
      only pressure in inactivating both B. cereus and S. warneri, the treatment of
      WBSDM at 400 MPa/ 60  degrees C/ 10 min is the most practical condition for
      postprocess of WBSDM after cooking. 

PMID- 25943210
TI  - Rapamycin Prolongs Cardiac Allograft Survival in a Mouse Model by Inducing
      Myeloid-Derived Suppressor Cells.
AB  - Mammalian target of rapamycin (mTOR) inhibitors are the main immunosuppressive
      drugs for organ transplant recipients. Nevertheless, the mechanisms by which mTOR
      inhibitors induce immunosuppression is not fully understood. Myeloid-derived
      suppressor cells (MDSCs) maintain host immunity; however, the relationship
      between mTOR inhibitors and MDSCs is unclear. Here, the results from a murine
      cardiac transplantation model revealed that rapamycin treatment (3 mg/kg,
      intraperitoneally on postoperative days 0, 2, 4, and 6) led to the recruitment of
      MDSCs and increased their expression of inducible nitric oxide synthase (iNOS).
      Immunohistochemical analysis revealed that rapamycin induced the migration of
      iNOS-expressing MDSCs into the subintimal space within the allograft vessels,
      resulting in a significant prolongation of graft survival compared with that in
      the untreated group (67 days vs. 7 days, respectively). These effects were
      counterbalanced by the administration of an anti-Gr-1, which reduced allograft
      survival to 21 days. Moreover, adoptive transcoronary arterial transfer of MDSCs
      from rapamycin-treated recipients prolonged allograft survival; this increase was
      reversed by the anti-Gr-1 antibody. Finally, co-administration of rapamycin and a
      mitogen-activated protein kinase kinase (MEK) inhibitor trametinib reversed
      rapamycin-mediated MDSC recruitment. Thus, the mTOR and Raf/MEK/extracellular
      signal regulated kinase (ERK) signaling pathways appear to play an important role
      in MDSC expansion. 

PMID- 25943209
TI  - Seeing Like a Geologist: Bayesian Use of Expert Categories in Location Memory.
AB  - Memory for spatial location is typically biased, with errors trending toward the
      center of a surrounding region. According to the category adjustment model (CAM),
      this bias reflects the optimal, Bayesian combination of fine-grained and
      categorical representations of a location. However, there is disagreement about
      whether categories are malleable. For instance, can categories be redefined based
      on expert-level conceptual knowledge? Furthermore, if expert knowledge is used,
      does it dominate other information sources, or is it used adaptively so as to
      minimize overall error, as predicted by a Bayesian framework? We address these
      questions using images of geological interest. The participants were experts in
      structural geology, organic chemistry, or English literature. Our data indicate
      that expertise-based categories influence estimates of location memory
      particularly when these categories better constrain errors than alternative
      ("novice") categories. Results are discussed with respect to the CAM. 

PMID- 25943211
TI  - Memory, emotion, and pupil diameter: Repetition of natural scenes.
AB  - Recent studies have suggested that pupil diameter, like the "old-new" ERP, may be
      a measure of memory. Because the amplitude of the old-new ERP is enhanced for
      items encoded in the context of repetitions that are distributed (spaced),
      compared to massed (contiguous), we investigated whether pupil diameter is
      similarly sensitive to repetition. Emotional and neutral pictures of natural
      scenes were viewed once or repeated with massed (contiguous) or distributed
      (spaced) repetition during incidental free viewing and then tested on an explicit
      recognition test. Although an old-new difference in pupil diameter was found
      during successful recognition, pupil diameter was not enhanced for distributed,
      compared to massed, repetitions during either recognition or initial free
      viewing. Moreover, whereas a significant old-new difference was found for erotic
      scenes that had been seen only once during encoding, this difference was absent
      when erotic scenes were repeated. Taken together, the data suggest that pupil
      diameter is not a straightforward index of prior occurrence for natural scenes. 

PMID- 25943208
TI  - The goose genome sequence leads to insights into the evolution of waterfowl and
      susceptibility to fatty liver.
AB  - BACKGROUND: Geese were domesticated over 6,000 years ago, making them one of the
      first domesticated poultry. Geese are capable of rapid growth, disease
      resistance, and high liver lipid storage capacity, and can be easily fed coarse
      fodder. Here, we sequence and analyze the whole-genome sequence of an
      economically important goose breed in China and compare it with that of
      terrestrial bird species. RESULTS: A draft sequence of the whole-goose genome was
      obtained by shotgun sequencing, and 16,150 protein-coding genes were predicted.
      Comparative genomics indicate that significant differences occur between the
      goose genome and that of other terrestrial bird species, particularly regarding
      major histocompatibility complex, Myxovirus resistance, Retinoic acid-inducible
      gene I, and other genes related to disease resistance in geese. In addition,
      analysis of transcriptome data further reveals a potential molecular mechanism
      involved in the susceptibility of geese to fatty liver disease and its associated
      symptoms, including high levels of unsaturated fatty acids and low levels of
      cholesterol. The results of this study show that deletion of the goose lep gene
      might be the result of positive selection, thus allowing the liver to adopt
      energy storage mechanisms for long-distance migration. CONCLUSIONS: This is the
      first report describing the complete goose genome sequence and contributes to
      genomic resources available for studying aquatic birds. The findings in this
      study are useful not only for genetic breeding programs, but also for studying
      lipid metabolism disorders.

PMID- 25943213
TI  - Home care work environment.

PMID- 25943212
TI  - CHL1, ITGB3 and SLC6A4 gene expression and antidepressant drug response: results
      from the Munich Antidepressant Response Signature (MARS) study.
AB  - AIM: The identification of antidepressant drugs (ADs) response biomarkers in
      depression is of high clinical importance. We explored CHL1 and ITGB3 expression
      as tentative response biomarkers. MATERIALS & METHODS: In vitro sensitivity to
      ADs, as well as gene expression and genetic variants of the candidate genes CHL1,
      ITGB3 and SLC6A4 were measured in lymphoblastoid cell lines (LCLs) of 58
      depressed patients. RESULTS: An association between the clinical remission of
      depression and the basal expression of CHL1 and ITGB3 was discovered. Individuals
      whose LCLs expressed higher levels of CHL1 or ITGB3 showed a significantly better
      remission upon AD treatment. In addition individuals with the CHL1 rs1516338 TT
      genotype showed a significantly better remission after 5 weeks AD treatment than
      those carrying a CC genotype. No association between the in vitro sensitivity of
      LCLs toward AD and the clinical remission could be detected. CONCLUSION: CHL1
      expression in patient-derived LCLs correlated with the clinical outcome. Thus, it
      could be a valid biomarker to predict the success of an antidepressant therapy.
      Original submitted 8 December 2014; Revision submitted 2 March 2015.

PMID- 25943215
TI  - Safe chemotherapy in the home environment.
AB  - The Oncology Nursing Society and the American Society of Clinical Oncology have
      established guidelines for the safe and effective use of chemotherapeutic
      medications in the acute and outpatient care settings. A review of literature was
      performed to determine the safe and effective administration of chemotherapy in
      the home environment. The administration of oral and intravenous chemotherapy in
      the home has become a common intervention for patients being treated for cancer
      based on patient preference, cost-effectiveness of healthcare delivery, and
      increasing demand for oncology services. Home healthcare nurses can greatly
      impact the management of adverse effects of chemotherapy in the home, increasing
      the quality of life and improving patient outcomes. 

PMID- 25943217
TI  - Telehealth etiquette in home healthcare: the key to a successful visit.
AB  - The use of telehealth by home healthcare agencies is growing. It has been shown
      to reduce rehospitalizations by up to 62%, reduce costs, and increase efficiency.
      Due to the use of telehealth technology, new and unique rules of etiquette must
      be followed to make both the patient and clinician comfortable and satisfied with
      the process. Little literature exists regarding telehealth etiquette. This
      article explores the techniques and methods that home care clinicians should
      utilize to assure that the telehealth experience is positive and effective. After
      providing a less successful scenario, steps for success are outlined and a
      suggested successful conclusion is provided for the scenario. Home care agencies
      will benefit greatly from expanding their ability to visit patients in different
      ways. Simple steps need to be taken to assure successful visits that follow the
      rules for assuring patient comfort, autonomy, and protection. 

PMID- 25943218
TI  - West Nile Virus: an overview.
AB  - West Nile Virus is the most frequent cause of arboviral disease in the United
      States. It was first identified in the United States in 1999. Since that time,
      each of the 48 contiguous states in the United States has seen the disease, and
      it has been found in 96% of the U.S. counties in infected humans, mosquitoes,
      birds, horses, or other mammals. Although most often the disease resolves on its
      own, patients can develop serious and life-threatening complications, and may
      need further monitoring and treatment. This article reviews the prevalence,
      transmission, signs and symptoms, complications, treatment, surveillance, and
      prevention of the disease. 

PMID- 25943219
TI  - Outcomes of usual versus a specialized falls and balance program in the home.
AB  - A retrospective cohort study with adjustment for baseline group differences was
      conducted to determine if there was a difference in Outcome and Information Data
      Set (OASIS-C) activities of daily living (ADL) outcomes as well as the duration
      and number of home care visits between usual home care rehabilitation services
      and a home care rehabilitation team that was specially trained in falls
      identification and prevention. Data from adult Medicare beneficiaries who were
      treated in a large multistate home care practice with at least one visit by a
      physical therapist were retrieved retrospectively for analysis (n = 3,907
      records). Patients identified as having multiple fall risk factors based on OASIS
      C assessment undergoing a specialized care program demonstrated greater
      improvements in mean total ADL scores after home healthcare rehabilitation
      services compared with subjects at fall risk receiving usual care.
      Interdisciplinary care delivered by a healthcare team specially trained in fall
      prevention appeared to decrease the number of home care visits and resulted in
      improved ADL OASIS-C outcome scores after adjustment for potential confounders. 

PMID- 25943220
TI  - Comprehensive foot care education in home-based settings: a tool for clinicians.
AB  - Prevention of diabetic foot ulcers and amputations does not receive the same
      priority as problem resolution in the primary care setting. Educating patients
      with diabetes about foot care in a home-based setting could enable the home
      healthcare clinician to provide information that could help reduce the risk of
      ulcerations and amputations. The development of an algorithm to aid clinicians in
      providing recommended education would enable clinicians to practice using the
      best-available evidence. 

PMID- 25943221
TI  - Gliflozins.

PMID- 25943222
TI  - ISMP Medication Errors.

PMID- 25943223
TI  - Urine specimen collection and transport.

PMID- 25943224
TI  - A day in the life of...A home healthcare director.

PMID- 25943225
TI  - Gentle teaching.

PMID- 25943226
TI  - The voice of the patient.

PMID- 25943227
TI  - Interprofessional care management: more than comparing notes.

PMID- 25943228
TI  - Residency and movement patterns of Arctic charr Salvelinus alpinus relative to
      major estuaries.
AB  - Estuarine residency and marine movements of 43 anadromous Arctic charr Salvelinus
      alpinus (mean +/- s.d. fork length = 523 +/- 97 mm) were examined using acoustic
      tracking in inner Frobisher Bay (IFB; 63 degrees  N; 68 degrees  W), Canada, from
      July to September 2008 and 2009. A mean +/- s.d. migration duration of 63 +/- 7
      days occurred from late June to early September. Detected S. alpinus were either
      continuously (maximum 34 days) or intermittently present in estuarine zones, on
      average residing approximately one third of time tracked and returning once every
      9 days. Significantly higher estuarine residency during the final 15 migration
      days suggested that a transition phase may occur prior to freshwater re-entry.
      Low travel rates during flood tide suggested individuals staged before accessing
      intertidal and estuarine zones. Although the two main estuaries were c. 22 km
      apart, 19% of tagged individuals used both. Individuals remained relatively close
      to freshwater overwintering systems, although late-migration inter-estuarine
      movements may have indicated natal homing. Approximately half of the individuals
      exhibited extra-estuarine travel, mostly during mid-migration, but remained
      within 3 km of shore ranging < 30 km straight line distance (SLD) of either
      estuary. It was concluded that IFB S. alpinus (1) spent a significant portion of
      their migration within or adjacent to the estuaries and (2) had a restricted
      marine distribution within 30 km SLD of the river mouths. 

PMID- 25943230
TI  - A different view on immunity: spatial mapping of human T cells over a lifetime.

PMID- 25943231
TI  - Macrophages in transplantation.

PMID- 25943232
TI  - Sir Roy Calne, artist with scalpel and brush, transplant pioneer, researcher,
      artist, lasker and pride of Britain awardee.

PMID- 25943233
TI  - Virtual populations, real decisions: making sense of stochastic simulation
      studies.

PMID- 25943234
TI  - The relative benefits and costs of solid phase bead technology to detect
      preformed donor specific antihuman leukocyte antigen antibodies in determining
      suitability for kidney transplantation.
AB  - BACKGROUND: Screening for donor-specific anti-HLA antibodies (DSA) using bead
      based multiplex assays to determine transplant suitability is standard practice
      in many countries. We compared the health benefits and costs of screening
      preformed DSA using bead-based assay as an add-on test to complement-dependent
      cytotoxicity (CDC) crossmatch with CDC crossmatch alone, and determined the
      optimal threshold to determine transplant suitability. METHODS: Three
      probabilistic Markov models were developed to compare bead-based assay with CDC
      and CDC alone. The model assumed a hypothetical cohort of 10,000 patients who
      received only a single kidney transplant and terminated when all patients were
      deceased. RESULTS: Assuming transplantation was permitted for recipients with no
      DSA or with a DSA mean fluorescence intensity (MFI) value of 500 or less,
      screening by bead-based assay and CDC saved 6.5 grafts and U.S. $1,192,303 per
      100 transplants compared with CDC alone. If the thresholds were increased to an
      MFI of 2000 or less and 5000 or less, an extra 6.4 and 6.1 grafts would be saved,
      with cost savings of U.S. $867,203 and U.S. $830,664 per 100 transplants compared
      with CDC alone. The total number of kidney transplants performed would have
      increased by 8 and 9, respectively, but at the expense of an extra 0.1 and 0.4
      graft lost per 100 transplants after 5 years. CONCLUSIONS: Screening using bead
      based assay is cost-saving and improves graft outcomes. The greatest benefits and
      cost-savings are achieved if transplantation occurs at a threshold of MFI of 500
      or less or in those without preformed DSA. Increasing the threshold to an MFI of
      2000 or less may provide an acceptable balance for improving transplant
      eligibility without compromising longer-term outcomes.

PMID- 25943235
TI  - Use of MALDI-TOF Mass Spectrometry to Assay the Transthyretin V30M Mutation in
      Serum From a Liver Transplant Donor: A Case Report.

PMID- 25943236
TI  - HbA1c Is Insensitive at Month 3 After Kidney Transplantation.

PMID- 25943237
TI  - The Authors' Reply: HbA1c Is Insensitive at Month 3 After Kidney Transplantation.

PMID- 25943238
TI  - Neuromyotonia with polyneuropathy, prominent psychoorganic syndrome, insomnia,
      and suicidal behavior without antibodies: a case report.
AB  - INTRODUCTION: Peripheral nerve hyperexcitability disorders are characterized by
      constant muscle fiber activity. Acquired neuromyotonia manifests clinically in
      cramps, fasciculations, and stiffness. In Morvan's syndrome the signs of
      peripheral nerve hyperexcitability are accompanied by autonomic symptoms, sensory
      abnormalities, and brain disorders. CASE PRESENTATION: A 70-year-old Caucasian
      man developed, in the course of 3 months, polyneuropathy with unpleasant
      dysesthesia of lower extremities and gradually increasing fasciculations, muscle
      stiffness and fatigue. Subsequently, he developed a prominent insomnia with
      increasing psychological changes and then he attempted a suicide.
      Electromyography confirmed a sensory-motor polyneuropathy of a demyelinating
      type. The findings included fasciculations as well as myokymia, doublets and
      multiplets, high frequency discharges, and afterdischarges, following motor nerve
      stimulation. No auto-antibodies were found either in his blood or cerebrospinal
      fluid. Magnetic resonance imaging of his brain showed small, unspecific, probably
      postischemic changes. A diagnosis of Morvan's syndrome was confirmed;
      immunoglobulin (2g/kg body weight) was applied intravenously, and, subsequently,
      carbamazepine 2 * 200 mg, venlafaxine 150 mg, and mirtazapine each night were
      prescribed. His sleep improved, suicidal tendencies stopped, less fasciculations
      occurred, and muscle hypertonia also improved. Hyperexcitation also partially
      remitted including the electromyography finding. CONCLUSIONS: We described here
      the case of a patient with Morvan's syndrome; his case is rare because of severe
      psychical changes with a suicide attempt, short admission to a psychiatric ward,
      prominent electromyographic changes, and because antibodies were not detected.
      After therapy with immunoglobulins followed by corticosteroids with sodium
      channel blocker, his motor, autonomic, psychical signs and symptoms, and
      electromyography changes substantially improved.

PMID- 25943239
TI  - Towards a paradigm shift in cancer screening: informed citizens instead of
      greater participation.

PMID- 25943240
TI  - An Extraordinary Association of Glomus Tumor and Pacinian Hyperplasia in the Hand
      of a Female Patient.
AB  - BACKGROUND: Glomus tumor is a benign neoplasm of the glomus body, a
      neuromyoarterial structure that regulates temperature and pressure in the
      cutaneous vasculature. Approximately 1%-4.5% of glomus tumors present in the
      hands of females; of these, 65% are seen in the subungual region of the index and
      long fingers. Pacinian hyperplasia is a benign lesion of the Pacinian corpuscle,
      a mechanoreceptor located in the subcutis of the hands and feet. METHODS: A 65
      year-old woman with a history of hand trauma and a 1-year chief complaint of
      tingling, pain, and burning sensations in her proximal thumb underwent
      exploration of the digital nerve after an x-ray and 2 magnetic resonance imaging
      examinations failed to detect a mass. Two lesions immediately adjacent to each
      other were excised. RESULTS: Microscopic examination showed Pacinian hyperplasia,
      and a second proliferation of solid epithelioid cells related to benign blood
      vessels. Immunohistochemistry confirmed the epithelioid cells to be strongly
      positive for smooth muscle actin, CD34, and type 4 collagen, which is consistent
      with the phenotype of a glomus tumor. The cells were negative for S100 protein.
      CONCLUSIONS: The association of glomus tumor with Pacinian hyperplasia has rarely
      been reported in the literature. We present another rare case to bring awareness
      to this differential diagnostic consideration.

PMID- 25943241
TI  - Dermatofibrosarcoma Protuberans of the Vulva With Myoid Differentiation.
AB  - Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft-tissue tumor
      characterized by a relatively high risk for local recurrence and low risk for
      metastasis. Many histopathologic variants of DFSP have been described, including
      the fibrosarcomatous and myoid variants, which may obscure the diagnosis in some
      cases, especially when arising in unusual locations. Of all the variants
      described so far, the only one with prognostic relevance is the FS-DFSP variant,
      which implies tumor progression and a higher possibility for metastasis. The
      authors report a case of a giant DFSP, located on the vulvar area, which
      histopathologically showed areas of fibrosarcomatous and myoid differentiation,
      and discuss the importance of the myoid variant in regards of the debated
      histogenesis of DFSP. 

PMID- 25943242
TI  - Atypical Spitz Tumor Arising on a Congenital Linear Plaque-Type Blue Nevus: A
      Case Report With a Review of the Literature on Plaque-Type Blue Nevus.
AB  - The plaque-type blue nevus (PTBN) is a rare variant of blue nevus, of which only
      a few reports are described. A nodular growth within a preexistent PTBN should
      always alert to the possibility of malignant transformation. The authors report
      the first case of an atypical Spitz tumor arising on a congenital linear PTBN in
      a 60-year-old woman. The diagnosis of "atypical Spitz tumor" is here used to
      describe a microscopic "gray zone" in which it is not possible to differentiate
      with adequate certainty between a Spitz nevus and a spitzoid melanoma. This
      report adds to and summarizes the small body of literature describing PTBN and
      discusses diagnostic and clinical implications. 

PMID- 25943243
TI  - Lentigo Maligna Melanoma With Local and Distant Blue Nevus-like Metastases.
AB  - Melanoma or melanoma metastases can rarely mimic blue nevi clinically and/or
      histologically, presenting a diagnostic pitfall for both the clinician and the
      dermatopathologist. We report a case of an invasive lentigo maligna melanoma with
      subsequent development of multiple, cutaneous blue nevus-like localized
      metastases followed by a distant metastasis, heralding widespread systemic
      metastases. 

PMID- 25943244
TI  - The essential role of SepF in mycobacterial division.
AB  - Mycobacteria lack several of the components that are essential in model systems
      as Escherichia coli or Bacillus subtilis for the formation of the divisome, a
      ring-like structure assembling at the division site to initiate bacterial
      cytokinesis. Divisome assembly depends on the correct placement of the FtsZ
      protein into a structure called the Z ring. Notably, early division proteins that
      assist in the localisation of the Z ring to the cytoplasmic membrane and modulate
      its structure are missing in the so far known mycobacterial cell division
      machinery. To find mycobacterium-relevant components of the divisome that might
      act at the level of FtsZ, a yeast two-hybrid screening was performed with FtsZ
      from Mycobacterium tuberculosis. We identified the SepF homolog as a new
      interaction partner of mycobacterial FtsZ. Depending on the presence of FtsZ,
      SepF-GFP fusions localised in ring-like structures at potential division sites.
      Alteration of SepF levels in Mycobacterium smegmatis led to filamentous cells,
      indicating a division defect. Depletion of SepF resulted in a complete block of
      division. The sepF gene is highly conserved in the M. tuberculosis complex
      members. We therefore propose that SepF is an essential part of the core division
      machinery in the genus Mycobacterium. 

PMID- 25943245
TI  - Tissue Doppler Imaging Measures Correlate Poorly with Left Ventricular Filling
      Pressures in Pediatric Cardiomyopathy.
AB  - SETTING: In adults with cardiomyopathy, tissue Doppler imaging (TDI) has been
      shown to correlate with left ventricular filling pressures (LVFPs) and has been
      advocated as a surrogate to catheterization. However, this has not been validated
      in children. DESIGN: This is a retrospective review of children <=18 years old
      with dilated, hypertrophic, restrictive, and left ventricular noncompaction
      cardiomyopathy who underwent cardiac catheterization within 3 months of an
      echocardiogram. Spearman's correlation coefficients were calculated to assess a
      correlation between LVFP and mitral inflow E/A ratio, lateral mitral E/E', and
      septal E/E'. RESULTS: Thirty-eight patients were included in the study; median
      age was 8.6 years old. The median LVFP was 19 mm Hg, median mean pulmonary artery
      pressure was 25 mm Hg, and median pulmonary vascular resistance index (PVRi) was
      2.4 Wu. There was no significant correlation between LVFP or PVRi with lateral
      mitral E/E' or septal E/E'. There was a positive correlation between LVFP and
      mitral inflow E/A ratio (rs = 0.59, P < .01). In a subgroup analysis of patients
      with hypertrophic or restrictive cardiomyopathy, there was a negative correlation
      (rs = 0.56, P = .02) between the mean pulmonary artery pressure and septal A'.
      CONCLUSIONS: TDI measures of diastolic function are not reliable surrogates for
      LVFP, mean pulmonary artery pressures, and PVRi at catheterization in children.

PMID- 25943247
TI  - Cutaneous manifestations in trisomy 13 mosaicism: A rare case and review of the
      literature.
AB  - Trisomy 13 mosaicism is a rare genetic disorder affecting a small minority of all
      trisomy 13 cases. It occurs when two cell populations that are karyotypically
      different are present in the same individual and are derived from a single
      zygote. As a rule, the phenotype is mitigated to a less dysmorphic appearance and
      longer survival, making genetic counseling a difficult task. Capillary
      hemangiomas are a common feature of full trisomy 13, seen in 27-56% of all cases.
      We report on an 18-months-old girl with extensive cutaneous anomalies, mild
      dysmorphic features, and slight psychomotor delay, without structural defects and
      provide an up-to-date review of all cases of trisomy 13 mosaicism with skin
      involvement. To our knowledge, this is the second clinical report of a patient
      with trisomy 13 mosaicism with hemangiomas and port wine stains, but no
      structural defects. (c) 2015 Wiley Periodicals, Inc. 

PMID- 25943246
TI  - MRS thermometry calibration at 3 T: effects of protein, ionic concentration and
      magnetic field strength.
AB  - MRS thermometry has been utilized to measure temperature changes in the brain,
      which may aid in the diagnosis of brain trauma and tumours. However, the
      temperature calibration of the technique has been shown to be sensitive to non
      temperature-based factors, which may provide unique information on the tissue
      microenvironment if the mechanisms can be further understood. The focus of this
      study was to investigate the effects of varied protein content on the calibration
      of MRS thermometry at 3 T, which has not been thoroughly explored in the
      literature. The effects of ionic concentration and magnetic field strength were
      also considered. Temperature reference materials were controlled by water
      circulation and freezing organic fixed-point compounds (diphenyl ether and
      ethylene carbonate) stable to within 0.2  degrees C. The temperature was measured
      throughout the scan time with a fluoro-optic probe, with an uncertainty of 0.16 
      degrees C. The probe was calibrated at the National Physical Laboratory (NPL)
      with traceability to the International Temperature Scale 1990 (ITS-90). MRS
      thermometry measures were based on single-voxel spectroscopy chemical shift
      differences between water and N-acetylaspartate (NAA), Delta(H20-NAA), using a
      Philips Achieva 3 T scanner. Six different phantom solutions with varying protein
      or ionic concentration, simulating potential tissue differences, were
      investigated within a temperature range of 21-42  degrees C. Results were
      compared with a similar study performed at 1.5 T to observe the effect of field
      strengths. Temperature calibration curves were plotted to convert Delta(H20-NAA)
      to apparent temperature. The apparent temperature changed by -0.2  degrees C/% of
      bovine serum albumin (BSA) and a trend of 0.5  degrees C/50 mM ionic
      concentration was observed. Differences in the calibration coefficients for the
      10% BSA solution were seen in this study at 3 T compared with a study at 1.5 T.
      MRS thermometry may be utilized to measure temperature and the tissue
      microenvironment, which could provide unique unexplored information for brain
      abnormalities and other pathologies.

PMID- 25943248
TI  - Some arguments in favor of a Myriophyllum aquaticum growth inhibition test in a
      water-sediment system as an additional test in risk assessment of herbicides.
AB  - The present study compares the practicability, reproducibility, power, and
      sensitivity of a Myriophyllum aquaticum growth inhibition test in a water
      sediment system with the recently accepted Myriophyllum spicatum test in an
      equivalent testing system and the standard Lemna sp. test. Special consideration
      was given to endpoints based on M. aquaticum control plant growth and variability
      of relative growth rate and yield: shoot length, fresh weight, dry weight, and
      root weight. Sensitivity analysis was based on tests performed with 3,5
      dichlorophenol, atrazine, isoproturon, trifluralin, 2,4-dichlorophenoloxyacetic
      acid, and dicamba. Growth rates for average M. aquaticum control plants were
      0.119 d(-1) and 0.112 d(-1), with average estimated doubling time 6.33 d and 6.74
      d for relative growth rate fresh weight and shoot length, respectively. Intrinsic
      variability of M. aquaticum endpoints was low: 12.9%, 12.5%, and 17.8% for
      relative growth rate shoot length, relative growth rate fresh weight and yield
      fresh weight, respectively. The power of the test was fairly high. When the most
      sensitive endpoints were used for comparison, the 2 Myriophyllum species were
      similarly sensitive, more sensitive (in the case of auxin simulators), or at
      least equally sensitive as Lemna minor to other tested herbicides. The M.
      aquaticum 10-d test with a 7-d exposure period in a water-sediment system has
      acceptable sensitivity and can provide repeatable, reliable, and reproducible
      results; therefore, it should not be disregarded as a good and representative
      additional test in environmental risk assessment.

PMID- 25943249
TI  - alpha-Tocopherol long-chain metabolite alpha-13'-COOH affects the inflammatory
      response of lipopolysaccharide-activated murine RAW264.7 macrophages.
AB  - SCOPE: Inflammatory response of macrophages is regulated by vitamin E forms. The
      long-chain metabolite alpha-13'-carboxychromanol (alpha-13'-COOH) is formed by
      hepatic alpha-tocopherol (alpha-TOH) catabolism and acts as a regulatory
      metabolite via pathways that are different from its metabolic precursor. METHODS
      AND RESULTS: Using semisynthetically-derived alpha-13'-COOH we profiled its
      action on LPS-induced expression of pro- and anti-inflammatory genes using RT
      qPCR and of key proteins by Western blotting. Effects on inflammatory response
      were assessed by measuring production of nitric oxide and prostaglandin (PG) E2 ,
      PGD2 , and PGF2alpha. alpha-13'-COOH inhibits proinflammatory pathways in LPS
      stimulated RAW264.7 macrophages more efficiently than alpha-TOH. Profiling
      inflammation-related genes showed significant blocking of interleukin (Il)1beta
      by the metabolite and its precursor as well, while upregulation of Il6 was not
      impaired. However, induction of Il10, cyclooxygenase 2 (Cox2) and inducible
      nitric oxide synthase (iNos) by LPS and consequently the formation of nitric
      oxide and PG was significantly reduced by alpha-13'-COOH. Interestingly, alpha
      13'-COOH acted independently from translocation of NFkappaB subunit p65.
      CONCLUSION: Our study sheds new light on the mode of action of alpha-TOH on the
      inflammatory response in macrophages, which may be mediated in vivo at least in
      part by its metabolite alpha-13'-COOH. Our data show that alpha-13'-COOH is a
      potent anti-inflammatory molecule.

PMID- 25943250
TI  - CDKN2a mutation-negative melanoma families have increased risk exclusively for
      skin cancers but not for other malignancies.
AB  - Germline CDKN2A mutations are found in 5-20% of melanoma families. Numerous
      studies have shown that carriers of CDKN2A mutations have increased risks of non
      melanoma cancers, but so far there have been no studies investigating cancer
      risks in CDKN2A wild type (wt) melanoma families. In this prospective cohort
      study, index melanoma cases (n = 224) and their first-degree relatives (n = 944)
      were identified from 154 confirmed CDKN2A wt melanoma families. Cancer diagnoses
      in family members and matched controls were obtained from the Swedish Cancer
      Registry. Relative risks (RR), odds ratios (OR) and two-sided 95% confidence
      intervals (95% CI) were calculated. In index cases and first-degree relatives,
      the prospective RR for melanoma was 56.9 (95% CI 31.4-102.1) and 7.0 (95% CI 4.2
      11.4), respectively, and for squamous cell skin cancers 9.1 (95% CI 6.0-13.7) and
      3.4 (95% CI 2.2-5.2), respectively. In neither group, elevated risks were seen
      for non-skin cancers. In a subgroup analysis, CDKN2A wt melanoma families with
      young (<40 years) melanoma cases were found to have increased risk of non-skin
      cancers (RR 1.5, 95% CI 1.0-1.5). Further, MC1R gene variants were increased in
      familial melanoma cases compared to controls (OR 2.4, 95% CI 1.6-3.4). Our
      findings suggest that in the majority of CDKN2A wt melanoma families, a
      segregation of variants in low-risk melanoma genes such as MC1R causes increased
      skin cancer susceptibility, rather than mutations in high-risk cancer
      predisposing genes, such mutations are more probable to be found in melanoma
      families with young melanoma cases. This study further supports an implication of
      CDKN2A mutation screening as a clinical test that determines counseling and
      follows up routines of melanoma families.

PMID- 25943251
TI  - Directed Neural Stem Cell Differentiation with a Functionalized Graphene Oxide
      Nanocomposite.
AB  - Neural stem cell (NSC) transplantation has the potential to restore function to
      diseased or damaged nervous tissue, but poor control over cell survival,
      differentiation, and maturation limits therapeutic prospects. Engineered
      scaffolds that have the ability to drive neural stem cell behavior can address
      these limitations facing cell transplantation. Conducting polymers, which have
      the ability to electrically interface with cells, are attractive scaffolding
      candidates, but they lack the capacity for simple covalent modification, which
      would enable surface patterning of biomolecules. In this work, the NSC
      scaffolding performance of a nanocomposite composed of conducting polymer
      poly(3,4-ethylenedioxythiophene) (PEDOT) and graphene oxide (GO) nanosheets
      (GO/PEDOT) is investigated. The GO/PEDOT material is nontoxic and improves NSC
      differentiation toward the neuronal lineage. Biomolecules interferon-gamma
      (IFNgamma) and platelet-derived growth factor (PDGF) that selectively promote
      neuronal or oligodendrocyte lineage differentiation, respectively, are covalently
      cross-linked to the surface of the GO/PEDOT nanocomposite via carboxylic acid
      functional groups provided by GO using carbodiimide chemistry. The surfaces
      support a larger population of neurons when modified with IFNgamma and a larger
      population of oligodendrocytes when modified by PDGF. This work demonstrates the
      customizability of GO/PEDOT for cell scaffolding applications and underlines its
      potential for controlling NSC behavior to improve therapeutic potential. 

PMID- 25943252
TI  - Understanding the Aldo-Enediolate Tautomerism of Glycolaldehyde in Basic Aqueous
      Solutions.
AB  - The biochemically important interconversion process between aldoses and ketoses
      is assumed to take place via 1,2-enediol or 1,2-enediolate intermediates, but
      such intermediates have never been isolated. The current work was undertaken in
      an attempt to detect the presence of the 1,2-enediol structure of glycolaldehyde
      in alkaline medium, actually a 1,2-enediolate, and to try to clarify the scarce
      data existing about both the formation of deprotonated enediol and the aldo
      enediolate equilibrium. The Raman spectra of neutral and basic solutions were
      recorded as a function of time for eleven days. Several bands associated with the
      presence of the enediolate were observed in alkaline medium. Glycolaldehyde
      exists as three different structures in aqueous solution at neutral pH, that is,
      hydrated aldehydes, aldehydes and dimers, with a respective ratio of
      approximately 4:0.25:1. Additionally, the formation of Z-enediolate forms takes
      place at basic pH, together with an increase in the concentration of aldehyde
      species, such as 2-oxoethan-1-olate, and a decrease in the concentrations of the
      hydrated aldehyde and dimeric forms. The theoretical ratio of ~1.5:1 for
      aldehyde:Z-enediolate reproduces the experimental Raman spectrum in basic medium,
      with an additional contribution of the previously mentioned ratio between the
      hydrated aldehyde and dimeric forms. Finally, Raman spectroscopy allowed us to
      monitor the enolization of this carbohydrate model and conclude that aldo-enediol
      tautomerism-formally aldo-enediolate-happens when a suitable amount of basic
      species is added. 

PMID- 25943253
TI  - Spontaneous self-coating of a water drop by flaky copper powders: critical role
      of the particle shape.
AB  - The self-coating process of solid particles over a liquid drop is important for
      the formation of a liquid marble. Generally, some external forces such as rolling
      or flipping are used to cover a drop by small particles. In this work, it is
      observed that flaky copper powders can spontaneously spread over the planar water
      surface and form a dense flat cluster with a fractal dimension of 2. Moreover,
      flaky copper powders can cover the water pendant and sessile drops spontaneously
      and rapidly. This powder-coated drop can roll on an inclined plane at a
      relatively high speed. However, spontaneous self-coating disappears for
      spheroidal copper powders. To explain our observations, the shape factors of
      particles are introduced into the spreading coefficient S for powders on the
      liquid surface. The flaky powders have the lowest shape factors and therefore
      spontaneous self-coating formation, with S > 0. 

PMID- 25943254
TI  - Turkish critical care nurses' views on end-of-life decision making and practices.
AB  - BACKGROUND: Life-sustaining treatments are increasingly used in intensive care
      units (ICUs) for EOL care, but the decision to use these may cause ethical
      issues. AIMS AND OBJECTIVES: The aim of this study was to investigate the views
      and practices of critical care nurses in Turkey on the end-of-life (EOL) care.
      DESIGN: This was a cross-sectional study. METHODS: The research was conducted in
      32 second- and third-level ICUs of 19 Ministry of Health research hospitals in
      Turkey. The Views of European Nurses in Intensive Care on EOL Care tool was used
      for data collection. RESULTS: The total sample size was 602. While half of the
      nurses stated that the withholding and withdrawal of life support were ethically
      different decisions, 40% felt both decisions were unethical. The expected quality
      of life as viewed by the patient, the medical team, the family and the nursing
      team (90.4%, 85.4%, and 83.4%, respectively) was an important factor in EOL
      decision making. The majority of the nurses (75.7%) were not directly involved in
      the EOL decision making and 78.4% of nurses were committed to family involvement
      in EOL decisions. When withdrawing treatment, 87.2% of ICU nurses agreed that the
      patient and family members should perform their final religious and spiritual
      duties. Further results showed that after withdrawing treatment, a majority of
      nurses (86%) agreed to continue pressure sore prevention, effective pain relief
      (85.5%), nutritional support (77.6%) and hydration (64.8%). Almost half (48.2%)
      indicated that keeping the patients in the ICU was unnecessary. CONCLUSION: ICU
      nurses expressed a range of experiences and practices regarding EOL care. ICU
      nurses should be more involved in the decision-making process about EOL care.
      RELEVANCE TO CLINICAL PRACTICE: Due to their unique relationship with patients,
      nurses should be involved in EOL care decision making; however, patients,
      families or nurses are not often involved in the decision-making process in
      Turkey.

PMID- 25943255
TI  - High-throughput sequencing reveals adaptation-induced mutations in pentose
      fermenting strains of Zymomonas mobilis.
AB  - Zymomonas mobilis is capable of producing ethanol at high rates and titers from
      glucose. This bacterium has previously been engineered to consume the pentose
      sugars xylose and arabinose, but the rate of consumption of these sugars is low.
      Recent research has utilized adaptive evolution to isolate strains of Z. mobilis
      capable of rapidly fermenting xylose. In this study, we also used adaptive
      evolution to isolate strains of Z. mobilis capable of rapidly fermenting xylose
      and arabinose. To determine the bottlenecks in pentose metabolism, we then used
      high-throughput sequencing to pinpoint the genetic changes responsible for the
      phenotypes of the adapted strains. We found that the transport of both xylose and
      arabinose through the native sugar transporter, Glf, limits pentose fermentations
      in Z. mobilis. We also found that mutations in the AddB protein increase plasmid
      stability and can reduce cellular aggregation in these strains. Consistent with
      previous research, we found that reduced xylitol production improves xylose
      fermentations in Z. mobilis. We also found that increased transketolase activity
      and reduced glyceraldehyde-3-phosphate dehydrogenase activity improve arabinose
      fermentations in Z. mobilis. Biotechnol.

PMID- 25943256
TI  - New Ti-decorated B40 fullerene as a promising hydrogen storage material.
AB  - The newly found B40 is the first experimentally observed all-boron fullerene and
      has potential applications in hydrogen storage. Here we investigate the binding
      ability and hydrogen storage capacity of Ti-decorated B40 fullerene based on DFT
      calculations. Our results indicate that Ti shows excellent binding capability to
      B40 compared with other transition metals. The B40 fullerene coated by 6 Ti atoms
      (Ti6B40) can store up to 34 H2 molecules, corresponding to a maximum gravimetric
      density of 8.7 wt%. It takes 0.2-0.4 eV/H2 to add one H2 molecule, which assures
      reversible storage of H2 molecules under ambient conditions. The evaluated
      reversible storage capacity is 6.1 wt%. Our results demonstrate that the new Ti
      decorated B40 fullerene is a promising hydrogen storage material with high
      capacity.

PMID- 25943257
TI  - Imaging phosphorylated peptide distribution in human lens by MALDI MS.
AB  - Phosphorylation plays vital roles in complex biological processes such as
      cellular growth, division and signaling transduction. However, due to the low
      ionization efficiency of phosphorylated peptides, it is still a huge challenge to
      obtain region-specific phosphorylated peptide distribution by imaging mass
      spectrometry. To achieve the on-tissue analysis of phosphorylated peptides, we
      took advantage of a graphene oxide-immobilized enzyme reactor to conduct the in
      situ digestion, followed by dephosphorylation treatment that removed the
      phosphate groups and thereby helped to improve the signal intensity of
      phosphorylated peptides. A visual representation of the phosphoproteome of a
      human lens was successfully mapped. Results showed that phosphorylated peptides
      localized mainly in the nucleus region of a healthy lens while the outer cortex
      is the dominant region for phosphorylated peptides of a cataractous lens. 

PMID- 25943258
TI  - Characterizing metabolic changes in human colorectal cancer.
AB  - Colorectal cancer (CRC) remains a leading cause of cancer death worldwide,
      despite the fact that it is a curable disease when diagnosed early. The
      development of new screening methods to aid in early diagnosis or identify
      precursor lesions at risk for progressing to CRC will be vital to improving the
      survival rate of individuals predisposed to CRC. Metabolomics is an advancing
      area that has recently seen numerous applications to the field of cancer
      research. Altered metabolism has been studied for many years as a means to
      understand and characterize cancer. However, further work is required to
      establish standard procedures and improve our ability to identify distinct
      metabolomic profiles that can be used to diagnose CRC or predict disease
      progression. The present study demonstrates the use of direct infusion traveling
      wave ion mobility mass spectrometry to distinguish metabolic profiles from CRC
      samples and matched non-neoplastic epithelium as well as metastatic and primary
      tumors at different stages of disease (T1-T4). By directly infusing our samples,
      the analysis time was reduced significantly, thus increasing the speed and
      efficiency of this method compared to traditional metabolomics platforms. Partial
      least squares discriminant analysis was used to visualize differences between the
      metabolic profiles of sample types and to identify the specific m/z features that
      led to this differentiation. Identification of the distinct m/z features was made
      using the human metabolome database. We discovered alterations in fatty acid
      biosynthesis and oxidative, glycolytic, and polyamine pathways that distinguish
      tumors from non-malignant colonic epithelium as well as various stages of CRC.
      Although further studies are needed, our results indicate that colonic epithelial
      cells undergo metabolic reprogramming during their evolution to CRC, and the
      distinct metabolites could serve as diagnostic tools or potential targets in
      therapy or primary prevention. Graphical Abstract Colon tissue biopsy samples
      were collected from patients after which metabolites were extracted via
      sonication. Two-dimensional data were collected via IMS in tandem with MS (IMMS).
      Data were then interpreted statistically via PLS-DA. Scores plots provided a
      visualization of statistical separation and groupings of sample types. Loading
      plots allowed identification of influential ion features. Lists of these features
      were exported and analyzed for specific differences. Direct comparisons of the
      ion features led to the identification and comparative analyses of candidate
      biomarkers. These differences were then expressed visually in charts and tables. 

PMID- 25943259
TI  - Liquid chromatography Orbitrap mass spectrometry with simultaneous full scan and
      tandem MS/MS for highly selective pesticide residue analysis.
AB  - This paper describes the application of LC/Q-Orbitrap MS for the analysis of
      pesticide residues in fruit and vegetable commodities. LC/Q-Orbitrap MS working
      in full scan simultaneously with a single MS/MS scan was used to analyse 139
      pesticide residues in QuEChERS extracts of tomato, pepper, orange and green tea.
      Full scan data were obtained at a resolution of 70,000 whereas MS/MS data were
      obtained at a resolution of 17,500. Quantitation and detection was carried out
      using full scan data while MS/MS data were used only for identification. MS/MS
      scans did not have a negative influence on quantitation under the applied
      conditions. Some peak area reproducibility problems were the consequence of the
      low sensitivity for some compounds (aldicarb, chlorpyriphos methyl, fenitrothion
      and fipronil) under the applied conditions. The relation between the operational
      parameters (viz. automatic gain control (AGC) target, maximum injection time
      (IT), underfill ratio, isolation window and apex trigger) and the number of
      automatically identified compounds was investigated. Mass error and minimal
      intensity of selected fragment ions were also studied. Various working modes were
      compared, such as full scan with single MS/MS scan and full scan with multiple
      MS/MS scans. In both cases, the number of automatically reported pesticides was
      the same. However full scan with single MS/MS scan ensured more points per peak
      in full scan mode and better peak area reproducibility. The evaluation of the
      identification and quantitation capabilities of the instrument was performed
      through the analysis of 100 real samples. The samples were also analysed by LC
      QqQ MS/MS and the results of both analytical systems were compared. The
      comparison revealed that the two instruments were consistent with each other.
      They found the same pesticides and neither false positive nor false negatives
      were reported. Nevertheless the Q-Orbitrap MS allowed one to work in high
      resolution mass spectrometry, increasing the selectivity and, in full scan mode,
      permitting the retrospective analysis of the data feature that cannot be achieved
      with QqQ. 

PMID- 25943260
TI  - Exploring LA-ICP-MS as a quantitative imaging technique to study nanoparticle
      uptake in Daphnia magna and zebrafish (Danio rerio) embryos.
AB  - The extent and the mechanisms by which engineered nanoparticles (ENPs) are
      incorporated into biological tissues are a matter of intensive research.
      Therefore, laser ablation coupled to inductively coupled plasma mass spectrometry
      (LA-ICP-MS) is presented for the detection and visualization of engineered
      nanoparticles (Al2O3, Ag, and Au) in ecotoxicological test organisms (Danio rerio
      and Daphnia magna). While ENPs are not taken up by the zebrafish embryo but
      attach to its chorion, incorporation into the gut of D. magna is clearly visible
      by a 50-MUm spot ablation of 40-MUm-thick organism sections. During laser
      ablation of the soft organic matrix, the hard ENPs are mobilized without a
      significant change in their size, leading to decreasing sensitivity with
      increasing size of ENPs. To compensate for these effects, a matrix-matched
      calibration with ENPs of the same size embedded in agarose gels is proposed.
      Based on such a calibration, the mass of ENPs within one organism section was
      calculated and used to estimate the total mass of ENPs per organism. Compared to
      the amount determined after acid digestion of the test organisms, recoveries of
      20-100% (zebrafish embryo (ZFE)) and of 4-230% (D. magna) were obtained with LODs
      in the low ppm range. It is likely that these differences are primarily due to an
      inhomogeneous particle distribution in the organisms and to shifts in the
      particle size distribution from the initial ENPs to those present in the
      organism. It appears that quantitative imaging of ENPs with LA-ICP-MS requires
      knowledge of the particle sizes in the biological tissue under study.

PMID- 25943261
TI  - Overcoming the equivalent-chain-length rule with pH-zone-refining countercurrent
      chromatography for the preparative separation of fatty acids.
AB  - Purification of individual fatty acids from vegetable oils by preparative liquid
      chromatography techniques such as countercurrent chromatography (CCC) is a
      challenging task due to the equivalent-chain-length (ECL) rule. It implies that
      one double bond equals two carbon atoms in the alkyl chain of a fatty acid and
      therefore causes co-elutions of saturated and unsaturated fatty acids.
      Accordingly, existing methods for the purification of individual fatty acids are
      cumbersome and time-consuming as two or more steps with different conditions are
      required. To avoid additional purification steps, we report a method utilizing pH
      zone-refining CCC which enabled the purification of all major fatty acids from
      sunflower oil (purities >95 %) in one step by circumventing co-elutions caused by
      the ECL rule. This method is based on the involvement of acid strength and
      hydrophobicity of fatty acids during the separation process. By exploiting the
      preparative character of the pH-zone-refining mode, a tenfold sample amount of
      free fatty acids from sunflower oil could be separated in comparison to regular
      CCC.

PMID- 25943262
TI  - Comparative study of the endoscope-based bevelled and volume fiber-optic Raman
      probes for optical diagnosis of gastric dysplasia in vivo at endoscopy.
AB  - This study aims to compare the diagnostic performance of the two different
      endoscope-based fiber-optic Raman probe designs (i.e., bevelled and volume Raman
      probes) for real-time, in vivo detection of gastric dysplasia at endoscopy. To
      conduct the clinical comparison, a total of 1,050 in vivo tissue Raman spectra
      (normal: n = 864; dysplasia: n = 186) were acquired from 66 gastric patients
      (normal: n = 48; dysplasia: n = 18) by using bevelled Raman probe, while a total
      of 1,913 in vivo tissue Raman spectra (normal: n = 1,786; dysplasia: n = 127)
      were acquired from 98 gastric patients (normal: n = 87; dysplasia: n = 11) by
      using volume Raman probe. The bevelled Raman probe provides approximately twofold
      improvements in tissue Raman-to-autofluorescence intensity ratios as compared to
      the use of volume Raman probe. Partial least squares discriminant analysis
      together with leave-one patient-out cross-validation on in vivo tissue Raman
      spectra acquired yields a diagnostic accuracy of 93.0 % (sensitivity of 92.5 %;
      specificity of 93.1 %) for differentiating gastric dysplasia from normal gastric
      tissue by using the bevelled fiber-optic Raman probe, which is superior to the
      diagnostic performance (accuracy of 88.4 %; sensitivity of 85.8 %; specificity of
      88.6 %) by using the volume Raman probe. This work demonstrates that the Raman
      spectroscopic technique coupled with bevelled fiber-optic Raman probe has great
      potential to enhance in vivo diagnosis of gastric precancer and early cancer at
      endoscopy. Graphical Abstract Comparison of in vivo gastric tissue Raman spectra
      acquired by using bevelled and volume fiber-optic Raman probes. 

PMID- 25943263
TI  - Development and validation of an UPLC-MS/MS assay for quantitative analysis of
      the ghrelin receptor inverse agonist PF-5190457 in human or rat plasma and rat
      brain.
AB  - PF-5190457 is a ghrelin receptor inverse agonist that is currently undergoing
      clinical development for the treatment of alcoholism. Our aim was to develop and
      validate a simple and sensitive assay for quantitative analysis of PF-5190457 in
      human or rat plasma and rat brain using liquid chromatography-tandem mass
      spectrometry. The analyte and stable isotope internal standard were extracted
      from 50 MUL plasma or rat brain homogenate by protein precipitation using 0.1%
      formic acid in acetonitrile. Chromatography was carried out on an Acquity UPLC
      BEH C18 (2.1 mm * 50 mm) column with 1.7 MUm particle size and 130 A pore size.
      The flow rate was 0.5 mL/min and total chromatographic run time was 2.2 min. The
      mobile phase consisted of a gradient mixture of water: acetonitrile 95:5% (v/v)
      containing 0.1% formic acid (solvent A) and 100% acetonitrile containing 0.1%
      formic acid (solvent B). Multiple reaction monitoring was carried out in positive
      electro-spray ionization mode using m/z 513.35 -> 209.30 for PF-5190457 and m/z
      518.47 -> 214.43 for the internal standard. The recovery ranged from 102 to 118%
      with coefficient of variation (CV) less than 6% for all matrices. The calibration
      curves for all matrices were linear over the studied concentration range (R(2) >=
      0.998, n = 3). The lower limit of quantification was 1 ng/mL in rat or human
      plasma and 0.75 ng/g in rat brain. Intra- and inter-run mean percent accuracies
      were between 85 and 115% and percent imprecision was <=15%. The assays were
      successfully utilized to measure the concentration of PF-5190457 in pre-clinical
      and clinical pharmacology studies of the compound.

PMID- 25943264
TI  - Enhanced Neural Reactivity to Threatening Faces in Anxious Youth: Evidence from
      Event-Related Potentials.
AB  - Anxiety disorders are characterized by enhanced reactivity to threat, and event
      related potentials (ERPs) are useful neural measures of the dynamics of threat
      processing. In particular, the late positive potential (LPP) is an ERP component
      that reflects sustained attention towards motivationally salient information.
      Previous studies in adults suggest that the LPP is enhanced to threatening
      stimuli in anxiety but blunted in depression; however, very little work has
      evaluated the LPP to threat in anxious youth. We measured the LPP during an
      emotional face-matching task in youth (age 7-19) with current anxiety disorders
      (n = 53) and healthy controls with no history of psychopathology (n = 37). We
      evaluated group differences, as well as the effect of depressive symptoms on the
      LPP. Youth with anxiety disorders exhibited enhanced LPPs to angry and fearful
      faces 1000-2000 ms after stimulus onset. Higher depressive symptoms were
      associated with reduced LPPs to angry faces across both groups. Enhanced LPPs to
      threatening faces were most apparent for social anxiety disorder, as opposed to
      generalized anxiety disorder or separation anxiety disorder. Results suggest the
      LPP may be a useful neural measure of threat reactivity in youth with anxiety
      disorders and highlight the importance of accounting for symptoms of both
      depression and anxiety when examining emotional processing.

PMID- 25943265
TI  - Nodules in scrotum. Manifestation of urothelial carcinoma.

PMID- 25943266
TI  - Current radiological techniques used to evaluate unilateral partial ureteral
      obstruction: an experimental rabbit study.
AB  - AIM: The aim of this study was to evaluate functional and prognostic benefits of
      Doppler ultrasonography (DU), diuretic renal scintigraphy (DRS), and magnetic
      resonance urography (MRU) during diagnosis and follow-up of ureteropelvic
      junction obstruction (UPJO) and to examine apoptosis rates caused by UPJO in an
      experimental rabbit model. METHOD: Twenty-four rabbits were divided randomly into
      two groups. The left kidneys of 15 rabbits from the first group underwent Ulm
      Miller surgery to create UPJO, whereas the left kidneys of nine rabbits from the
      second group underwent sham surgery. A pressure flow study (Whitaker's test) was
      done during postoperative week 6. Based on the Whitaker test, the DU, DRS, and
      MRU findings were compared. The number of apoptotic renal cells was counted after
      death. RESULT: The Whitaker test run during postoperative week 6 revealed
      obstructions in 15 rabbits from group 1; the nine rabbits of the sham group had
      no obstructions. Sensitivity and specificity of DRS were 93.3 and 88.8 %,
      respectively, and those of MRU were 93.3 and 88.8 %, respectively. The
      postoperative mean RI values were significantly higher than the preoperative
      values, associated with sensitivity of 86.6 % and specificity of 77.5 % for
      detecting UPJO. DRS, MRU, and RI could not predict UPJO in one (8 %), one (8 %),
      and two (16 %) kidneys, respectively. Likelihood ratio (LR) was 8.4 for MRU and
      scintigraphy, while for RI, LR was 3.9. Pathology specimens revealed that all
      kidneys with UPJO underwent apoptosis, and the number of apoptotic cells was
      significantly higher on the UPJO-created side than on the contralateral and in
      the sham group (p < 0.05). No test predicted all apoptosis related to UPJO.
      CONCLUSION: The RI, DRS, and DMRU results correlated with the pressure flow
      results for detecting UPJO. No single radiological technique predicted all
      initial UPJO-created kidneys that concluded with apoptosis. Further studies are
      required to seek with better methods for diagnosing an obstruction or to define a
      combination of radiological techniques aiding in the management decision.

PMID- 25943267
TI  - Backbone assignment and secondary structure of the PLAT domain of human
      polycystin-1.
AB  - Polycystin-1 is a large transmembrane protein mutated in the common genetic
      disorder autosomal dominant polycystic kidney disease. One of the predicted
      intracellular domains of polycystin-1 is PLAT (Polycystin-1, Lipoxygenase and
      Alpha Toxin), which consists of 116 amino acids and is anchored to the membrane
      by linkers at both ends. It is predicted to have a large number of hydrophobic
      residues on the surface. Assignment of the NMR spectrum was hampered by
      considerable line broadening, and hence a programme of site-directed mutagenesis
      and searching for suitable solution conditions was undertaken. The optimum
      construct required fusion of the GB1 domain at the N-terminus and a His tag at
      the C-terminus, and proved to have several additional amino acids at both ends
      beyond the canonical domain boundaries, as well as mutation of W3128 to alanine.
      Optimum solubility required 500 mM sodium chloride, and usable spectra could only
      be obtained by perdeuteration. Backbone assignment was made using standard triple
      resonance spectra and is 88 % complete. The chemical shifts obtained suggest that
      a loop consisting of residues 3223-3228 is mobile in solution, and that the
      protein is similar in structure to a prediction produced by Swiss-Model based on
      the structure of a homologous protein. 

PMID- 25943268
TI  - (1)H, (13)C and (15)N resonance assignments of sigma(S) activating protein Crl
      from Salmonella enterica serovar Typhimurium.
AB  - The general stress response in Enterobacteria, like Escherichia coli or
      Salmonella, is controlled by the transcription factor sigma(S), encoded by the
      rpoS gene, which accumulates during stationary phase growth and associates with
      the core RNA polymerase enzyme (E) to promote transcription of genes involved in
      cell survival. Tight regulation of sigma(S) is essential to preserve the balance
      between self-preservation under stress conditions and nutritional competence in
      the absence of stress. Whereas sigma factors are generally inactivated upon
      interaction with anti-sigma proteins, sigma(S) binding by the Crl protein
      facilitates the formation of the holoenzyme Esigma(S), and therefore sigma(S)
      controlled transcription. Previously, critical residues in both Crl and sigma(S)
      were identified and assigned to the binding interface in the Crl-sigma(S)
      complex. However, high-resolution structural data are missing to fully understand
      the molecular mechanisms underlying sigma(S) activation by Crl, in particular the
      possible role of Crl in triggering domain rearrangements in the multi-domain
      protein sigma(S). Here we provide the (1)H, (13)C and (15)N resonance assignments
      of Salmonella enterica serovar Typhimurium Crl, as a starting point for CrlSTM
      structure determination and further structural investigation of the CrlSTM-sigma
      STM (S) complex. 

PMID- 25943269
TI  - INF2 mutations associated with dominant inherited intermediate Charcot-Marie
      Tooth neuropathy with focal segmental glomerulosclerosis in two Chinese patients.
AB  - Recently, mutations in the inverted formin 2 (INF2) gene have been indentified in
      patients with dominant inherited intermediate Charcot-Marie-Tooth neuropathy (DI
      CMT) with focal segmental glomerulosclerosis (FSGS). We report clinical and nerve
      pathological changes in two Chinese patients. Case 1 is 27 years old and
      presented with distal muscle weakness and atrophy of legs at the age of 13 and
      renal failure at the age of 26. Three of his family members died due to pure
      renal failure. Case 2 is 22 years old and presented with distal muscle weakness
      and atrophy of the legs with transient attacks of difficulty in speaking at age
      17. Proteinuria was found by routine urine test at the same time. Sural nerve
      biopsy revealed moderate-to-severe loss of myelinated fibers with union bulbs and
      regeneration clusters in both patients. Ultrastructurally, numerous elongated
      extensions of Schwann cells of unmyelinated fibers could be seen in both
      patients. INF2 gene mutation screening revealed c.451 T>C in case 1 and c.341 G>A
      in case 2. This is the first report of Chinese patients with INF2-related DI-CMT.
      The c.451 T>C mutant was responsible for both isolated FSGS and a dual phenotype
      of FSGS and neuropathy within one family. Intrafamilial variability can be found
      with the same INF2 mutation. The CNS manifestations further broadened the
      clinical spectrum of INF2- associated disorders. 

PMID- 25943270
TI  - A 29-year-old pregnant woman with worsening left hemiparesis, encephalopathy, and
      hemodynamic instability: a case report of subacute sclerosing panencephalitis.
AB  - A 29-year-old pregnant woman developed progressively worsening encephalopathy,
      left hemiparesis, and hemodynamic instability over a 6-week period. Initial brain
      MRI and work-up for infectious and autoimmune causes were normal, although
      elevated IgG and oligoclonal bands were seen on analysis of the cerebrospinal
      fluid (CSF). After uncomplicated spontaneous delivery of a preterm healthy
      infant, her condition worsened. Repeat brain MRI demonstrated generalized volume
      loss and evidence of corticospinal tract degeneration. She underwent a brain
      biopsy, which showed characteristic viral inclusions of the type seen in subacute
      sclerosing panencephalitis (SSPE). The diagnosis was confirmed by
      immunohistochemistry and electron microscopy, and additional CSF analysis also
      showed markedly elevated IgG titer for measles. Sequence analysis of the
      nucleoprotein gene N-450 demonstrated a close relationship to the sequences of
      viruses in genotype D7. This case documents an ~ 6-month progression to death of
      SSPE in a pregnant woman. 

PMID- 25943271
TI  - Rapidly progressive dementia with psychotic onset in a patient with the C9ORF72
      mutation.

PMID- 25943272
TI  - Long-lived plasma cells are generated in mucosal immune responses and contribute
      to the bone marrow plasma cell pool in mice.
AB  - During systemic immune responses, plasma blasts are generated in secondary
      lymphoid organs and migrate to the bone marrow, where they can become long-lived,
      being responsible for the maintenance of long-term antibody titers. Plasma blasts
      generated in mucosal immune responses of the small intestine home to the lamina
      propria (LP), producing mainly immunoglobulin A. The migration of these antibody
      secreting cells is well characterized during acute immune responses. Less is
      known about their lifetime and contribution to the long-lived bone marrow
      compartment. Here we investigate the lifetime of plasma cells (PCs) and the
      relationship between the PC compartments of the gut and bone marrow after oral
      immunization. Our findings indicate that PCs in the LP can survive for extended
      time periods. PCs specific for orally administered antigens can be detected in
      the bone marrow for at least 9 months after immunization, indicating that the
      mucosal PC compartment can contribute to the long-lived PC pool in this organ,
      independent of the participation of splenic B cells. Our findings suggest that
      the compartmentalization between mucosal and systemic PC pools is less strict
      than previously thought. This may have implications for the development of
      vaccines as well as for autoantibody-mediated diseases. 

PMID- 25943273
TI  - Intestinal barrier loss as a critical pathogenic link between inflammatory bowel
      disease and graft-versus-host disease.
AB  - Compromised intestinal barrier function is a prominent feature of inflammatory
      bowel disease (IBD). However, links between intestinal barrier loss and disease
      extend much further, including documented associations with celiac disease, type
      I diabetes, rheumatoid arthritis, and multiple sclerosis. Intestinal barrier loss
      has also been proposed to have a critical role in the pathogenesis of graft
      versus-host disease (GVHD), a serious, potentially fatal consequence of
      hematopoietic stem cell transplantation. Experimental evidence has begun to
      support this view, as barrier loss and its role in initiating and establishing a
      pathogenic inflammatory cycle in GVHD is emerging. Here we discuss similarities
      between IBD and GVHD, mechanisms of intestinal barrier loss in these diseases,
      and the crosstalk between barrier loss and the immune system, with a special
      focus on natural killer (NK) cells. Unanswered questions and future research
      directions on the topic are discussed along with implications for treatment. 

PMID- 25943274
TI  - Tissue heme oxygenase-1 exerts anti-inflammatory effects on LPS-induced pulmonary
      inflammation.
AB  - Heme oxygenase-1 (HO-1) has been shown to display anti-inflammatory properties in
      models of acute pulmonary inflammation. For the first time, we investigated the
      role of leukocytic HO-1 using a model of HO-1(flox/flox) mice lacking leukocytic
      HO-1 that were subjected to lipopolysaccharide (LPS)-induced acute pulmonary
      inflammation. Immunohistology and flow cytometry demonstrated that activation of
      HO-1 using hemin decreased migration of polymorphonuclear leukocytes (PMNs) to
      the lung interstitium and bronchoalveolar lavage (BAL) in the wild-type and,
      surprisingly, also in HO-1(flox/flox) mice, emphasizing the anti-inflammatory
      potential of nonmyeloid HO-1. Nevertheless, hemin reduced the CXCL1, CXCL2/3,
      tumor necrosis factor-alpha (TNFalpha), and interleukin 6 (IL6) levels in both
      animal strains. Microvascular permeability was attenuated by hemin in wild-type
      and HO-1(flox/flox) mice, indicating a crucial role of non-myeloid HO-1 in
      endothelial integrity. The determination of the activity of HO-1 in mouse lungs
      revealed no compensatory increase in the HO-1(flox/flox) mice. Topical
      administration of hemin via inhalation reduced the dose required to attenuate PMN
      migration and microvascular permeability by a factor of 40, emphasizing its
      clinical potential. In addition, HO-1 stimulation was protective against
      pulmonary inflammation when initiated after the inflammatory stimulus. In
      conclusion, nonmyeloid HO-1 is crucial for the anti-inflammatory effect of this
      enzyme on PMN migration to different compartments of the lung and on
      microvascular permeability. 

PMID- 25943276
TI  - Ozone-induced stomatal sluggishness changes carbon and water balance of temperate
      deciduous forests.
AB  - Tropospheric ozone concentrations have increased by 60-100% in the Northern
      Hemisphere since the 19(th) century. The phytotoxic nature of ozone can impair
      forest productivity. In addition, ozone affects stomatal functions, by both
      favoring stomatal closure and impairing stomatal control. Ozone-induced stomatal
      sluggishness, i.e., a delay in stomatal responses to fluctuating stimuli, has the
      potential to change the carbon and water balance of forests. This effect has to
      be included in models for ozone risk assessment. Here we examine the effects of
      ozone-induced stomatal sluggishness on carbon assimilation and transpiration of
      temperate deciduous forests in the Northern Hemisphere in 2006-2009 by combining
      a detailed multi-layer land surface model and a global atmospheric chemistry
      model. An analysis of results by ozone FACE (Free-Air Controlled Exposure)
      experiments suggested that ozone-induced stomatal sluggishness can be
      incorporated into modelling based on a simple parameter (gmin, minimum stomatal
      conductance) which is used in the coupled photosynthesis-stomatal model. Our
      simulation showed that ozone can decrease water use efficiency, i.e., the ratio
      of net CO2 assimilation to transpiration, of temperate deciduous forests up to
      20% when ozone-induced stomatal sluggishness is considered, and up to only 5%
      when the stomatal sluggishness is neglected. 

PMID- 25943277
TI  - Defect-related luminescent mesoporous silica nanoparticles employed for novel
      detectable nanocarrier.
AB  - Uniform and well-dispersed walnut kernel-like mesoporous silica nanoparticles
      (MSNs) with diameters about 100 nm have been synthesized by a templating sol-gel
      route. After an annealing process, the as-obtained sample (DLMSNs) inherits the
      well-defined morphology and good dispersion of MSNs, and exhibits bright white
      blue luminescence, higher specific surface area and pore volume, and better
      biocompatibility. The drug loading and release profiles show that DLMSNs have
      high drug loading capacity, and exhibit an initial burst release followed by a
      slow sustained release process. Interestingly, the luminescence intensity of the
      DLMSNs-DOX system increases gradually with the increase of cumulative released
      DOX, which can be verified by the confocal laser scanning images. The drug
      carrier DLMSNs can potentially be applied as a luminescent probe for monitoring
      the drug release process. Moreover, the DLMSNs-DOX system exhibits potent
      anticancer effect against three kinds of cancer cells (HeLa, MCF-7, and A549
      cells). 

PMID- 25943275
TI  - Chemokine-adjuvanted electroporated DNA vaccine induces substantial protection
      from simian immunodeficiency virus vaginal challenge.
AB  - There have been encouraging results for the development of an effective HIV
      vaccine. However, many questions remain regarding the quality of immune responses
      and the role of mucosal antibodies. We addressed some of these issues by using a
      simian immunodeficiency virus (SIV) DNA vaccine adjuvanted with plasmid-expressed
      mucosal chemokines combined with an intravaginal SIV challenge in rhesus macaque
      (RhM) model. We previously reported on the ability of CCR9 and CCR10 ligand (L)
      adjuvants to enhance mucosal and systemic IgA and IgG responses in small animals.
      In this study, RhMs were intramuscularly immunized five times with either DNA or
      DNA plus chemokine adjuvant delivered by electroporation followed by challenge
      with SIVsmE660. Sixty-eight percent of all vaccinated animals (P<0.01) remained
      either uninfected or had aborted infection compared with only 14% in the vaccine
      naive group. The highest protection was observed in the CCR10L chemokines group,
      where six of nine animals had aborted infection and two remained uninfected,
      leading to 89% protection (P<0.001). The induction of mucosal SIV-specific
      antibodies and neutralization titers correlated with trends in protection. These
      results indicate the need to further investigate the contribution of chemokine
      adjuvants to modulate immune responses and the role of mucosal antibodies in
      SIV/HIV protection. 

PMID- 25943278
TI  - Alcopops, taxation and harm: a segmented time series analysis of emergency
      department presentations.
AB  - BACKGROUND: In Australia, a Goods and Services Tax (GST) introduced in 2000 led
      to a decline in the price of ready-to-drink (RTD) beverages relative to other
      alcohol products. The 2008 RTD ("alcopops") tax increased RTD prices. The
      objective of this study was to estimate the change in incidence of Emergency
      Department (ED) presentations for acute alcohol problems associated with each
      tax. METHODS: Segmented regression analyses were performed on age and sex
      specific time series of monthly presentation rates for acute alcohol problems to
      39 hospital emergency departments across New South Wales, Australia over 15
      years, 1997 to 2011. Indicator variables represented the introduction of each
      tax. Retail liquor turnover controlled for large-scale economic factors such as
      the global financial crisis that may have influenced demand. Under-age (15-17
      years) and legal age (18 years and over) drinkers were included. RESULTS: The GST
      was associated with a statistically significant increase in ED presentations for
      acute alcohol problems among 18-24 year old females (0 . 14/100,000/month, 95% CI
      0 . 05-0 . 22). The subsequent alcopops tax was associated with a statistically
      significant decrease in males 15-50 years, and females 15-65 years, particularly
      in 18-24 year old females (-0 . 37/100,000/month, 95% CI -0 . 45 to -0 . 29). An
      increase in retail turnover of liquor was positively and statistically
      significantly associated with ED presentations for acute alcohol problems across
      all age and sex strata. CONCLUSIONS: Reduced tax on RTDs was associated with
      increasing ED presentations for acute alcohol problems among young women. The
      alcopops tax was associated with declining presentations in young to middle-aged
      persons of both sexes, including under-age drinkers.

PMID- 25943279
TI  - Hemospray rescue treatment of severe refractory bleeding associated with ischemic
      colitis: a case series.

PMID- 25943280
TI  - Undergraduate nursing students' experiences when examining nursing skills in
      clinical simulation laboratories with high-fidelity patient simulators: A
      phenomenological research study.
AB  - Simulation has become a widely used and established pedagogy for teaching
      clinical nursing skills. Nevertheless, the evidence in favour of this pedagogical
      approach is weak, and more knowledge is needed in support of its use. The aim of
      this study was (a) to explore the experiences of undergraduate nursing students
      when examining knowledge, skills and competences in clinical simulation
      laboratories with high-fidelity patient simulators and (b) to analyse these
      students' learning experiences during the examination. A phenomenological
      approach was used, and qualitative interviews were conducted among 23 second-year
      undergraduate nursing students-17 women and 6 men. The findings revealed that,
      irrespective of whether they passed or failed the examination, it was experienced
      as a valuable assessment of the students' knowledge and skills. Even if the
      students felt that the examination was challenging, they described it as a
      learning opportunity. In the examination, the students were able to integrate
      theory with practice, and earlier established knowledge was scrutinised when
      reflecting on the scenarios. The examination added aspects to the students'
      learning that prepared them for the real world of nursing in a safe environment
      without risking patient safety. The study findings suggest that examinations in
      clinical simulation laboratories can be a useful teaching strategy in nursing
      education. The use of high-fidelity patient simulators made the examination
      authentic. The reflections and feedback on the scenario were described as
      significant for the students' learning. Undergraduate nursing students can
      improve their knowledge, understanding, competence and skills when such
      examinations are performed in the manner used in this study. 

PMID- 25943282
TI  - Erratum to: panobinostat: first global approval.

PMID- 25943281
TI  - Treatment of hepatitis C in patients with cirrhosis: remaining challenges for
      direct-acting antiviral therapy.
AB  - Chronic hepatitis C virus (HCV) infection is a major global health concern,
      resulting in significant morbidity and mortality. Treatment using interferon
      based therapy in patients with HCV-related cirrhosis has been problematic due to
      toxicity and poor tolerability. Furthermore, interferon therapy is
      contraindicated in those with advanced cirrhosis or clinical decompensation, who
      are arguably the group most in need of viral eradication. The arrival of the
      direct-acting antiviral (DAA) era has resulted in the development of well
      tolerated and highly effective interferon-free drug regimens that promise to
      dramatically change the therapeutic landscape for those with advanced HCV-related
      liver disease, including patients with clinical decompensation or pre-liver
      transplantation. Many successful DAA combinations have emerged; however, a number
      of challenges remain including the establishment of the optimal treatment
      duration, the ideal combination of drug classes and determining the role of
      ribavirin. Moreover, the identification of treatment-experienced patients with
      genotype 3 HCV cirrhosis as a difficult-to-treat subgroup is a significant
      impediment to overcome, as are those who have failed prior DAA therapy. Despite
      these barriers, the ongoing prolific development of safe and effective DAA
      combinations indicates the future is optimistic for the ultimate goal of HCV
      eradication.

PMID- 25943283
TI  - Neuroprotective effects of MK-801 against traumatic brain injury in immature
      rats.
AB  - Traumatic brain injury (TBI) is a major health problem in pediatric ages and also
      has major social, economic, and emotional outcomes, with diverse sequelae in many
      spheres of everyday life. We aimed to investigate the effect of MK-801, a
      competitive NMDA receptor antagonist, on hippocampal damage and behavioral
      deficits on 10-day-old rat pups subjected to contusion injury. The aims of the
      present study were to determine: (i) the short term effects of MK-801 on
      hippocampal BDNF, NGF and NMDA receptor immunoreactivity and neuron density in
      hippocampus (ii) long term effects of MK-801 on cognitive dysfunction following
      TBI in the immature rats. MK-801, was injected intraperitoneally at the doses of
      1mg/kg of body weight immediately after induction of traumatic injury.
      Hippocampal damage was examined by cresyl violet staining, BDNF, NGF and NMDAR
      receptor immunohistochemistry on P10 day and behavioral alterations were
      evaluated using elevated plus maze and novel object recognition tests two months
      after the trauma. Histopathological and immunohistochemical evaluations showed
      that treatment with a single dose of 1mg/kg MK-801 (i.p.) significantly
      ameliorated the trauma induced hippocampal neuron loss and decreased BDNF, NGF
      and NMDAR expressions in CA1, CA3 and DG hippocampal brain regions. Additionally,
      treatment with MK-801 ameliorated anxiety and hippocampus dependent memory of
      animals subjected to trauma. These results show that acute treatment of MK-801
      has a neuroprotective role against trauma induced hippocampal neuron loss and
      associated cognitive impairment in immature rats. 

PMID- 25943284
TI  - Rapid induction of granule cell elimination in the olfactory bulb by noxious
      stimulation in mice.
AB  - Elimination of granule cells (GCs) in the olfactory bulb (OB) is not a continuous
      event but is rather promoted during short time windows associated with the
      animal's behavior. We previously showed that apoptotic GC elimination is enhanced
      during food eating and subsequent rest or sleep, and that top-down inputs from
      the olfactory cortex (OC) to the OB during the postprandial period are the
      crucial signal promoting GC elimination. However, whether enhanced GC elimination
      occurs during behaviors other than postprandial behavior is not clear. Here, we
      investigated whether exposure to noxious stimulation promotes apoptotic GC
      elimination in mice. Mice were delivered a brief electrical foot shock, during
      and immediately after which they showed startle and fear responses. Surprisingly,
      the number of apoptotic GCs increased 2-fold within 10 min after the start of
      foot shock delivery. This enhancement of GC apoptosis was significantly
      suppressed by injection of the GABAA receptor agonist muscimol in the OC, despite
      these muscimol-injected mice showing similar behavioral responses by foot shock
      as control mice. These results indicate that GC elimination is promoted in foot
      shock-delivered mice within a short time period of startle and fear responses.
      They also indicate that OC activity plays a central role in the enhanced GC
      elimination during this period, as is also the case in GC elimination during the
      postprandial period.

PMID- 25943285
TI  - Exploring alternate specifications to explain agency-level effects in placement
      decisions regarding Aboriginal children: Further analysis of the Canadian
      Incidence Study of Reported Child Abuse and Neglect Part C.
AB  - A series of papers using data from the Canadian Incidence Study of Reported Child
      Abuse and Neglect (CIS) explored the influence of clinical and organizational
      characteristics on the decision to place Aboriginal children in out-of-home
      placements at the conclusion of child maltreatment investigations. The purpose of
      this paper is to further explore a consistent finding of the previous analyses:
      the proportion of investigations involving Aboriginal children at a child welfare
      agency is associated with placement for all children in that agency. CIS-2008
      data were used in the analysis, which allowed for inclusion of previously
      unavailable organizational and contextual variables. Multi-level statistical
      models were developed to analyze the influence of clinical and organizational
      variables on the placement decision. Final models revealed that the proportion of
      investigations conducted by the child welfare agency involving Aboriginal
      children was again a key agency-level predictor of the placement decision for any
      child served by the agency. Specifically, the higher the proportion of
      investigations of Aboriginal children, the more likely placement was to occur for
      any child. Further, this analysis demonstrated that structure of governance, an
      organizational-level variable not available in previous cycles of the CIS, is an
      important agency-level predictor of out-of-home placement. Further analysis is
      needed to fully understand individual and organizational level variables that may
      influence decisions regarding placement of Aboriginal children. 

PMID- 25943286
TI  - Extracapillary proliferation is an independent predictive factor in
      Immunoglobulin A nephropathy.
AB  - BACKGROUND: Oxford classification of Immunoglobulin A Nephropathy (IgAN)
      identifies four pathological features as predictors of renal outcome (MEST
      score): mesangial proliferation (M); endocapillary proliferation (E); segmental
      glomerulosclerosis (S); tubular atrophy/interstitial fibrosis (T). In particular
      extracapillary proliferation (Ex) was not considered as an independent
      histological variable predicting renal outcome. Recently the VALIGA study
      provided a validation of the Oxford classification in a large European cohort of
      IgAN patients and re-stated that Ex is not associated with a worse renal
      prognosis. We propose a retrospective study to evaluate the predictive value of
      the MEST-score in a multi-centre, single region group of patients from central
      Italy and in addition, to investigate Ex as a marker predicting renal outcome.
      METHODS: One hundred and seven patients were enrolled in this study. Clinical
      data of each patient were available at diagnosis and follow-up. The median age at
      diagnosis was 36.7 years; 72% of the patients were males. Histological parameters
      were those included in the MEST-score of the Oxford classification; in addition,
      Ex was also assessed. RESULTS: Multiple linear regression models for survey were
      used. Statistical analysis showed a correlation between the progression of renal
      decline, in terms of estimated glomerular filtration rate (slope eGFR), and M, S,
      T. Differently from Oxford and VALIGA studies, no correlation was found with E,
      while Ex correlated with a decline of eGFR. CONCLUSIONS: Our results suggest that
      Ex represents an additional independent variable associated with a faster decline
      of renal function in IgAN.

PMID- 25943287
TI  - Treatment and disposal of tyres: Two EU approaches. A review.
AB  - The treatment and disposal of tyres from vehicles has long been of considerable
      environmental importance. The main problem lies in the mixed composition of the
      tyres. Studies have been undertaken to modify the structure of the tyres,
      especially with reference to the percentage of granulated rubber incorporated, in
      order to improve their performance, and also to reduce their environmental impact
      during normal functioning (noise, particulates, etc.) and facilitate recycling
      and final disposal. The aim of the present study is to review and compare how
      used tyres are treated and disposed of in two different EU countries. The first
      is Italy, which has been part of the European Union since its inception, and has
      important industrial traditions. The second is Romania, an emerging country which
      recently became part of the EU, and whose economic and industrial development has
      had a major boost in recent years, with a strong growth in waste production,
      together with consumption in urban areas. The occasion was useful to consider the
      situation concerning the evolution of the different aspects related to the
      management of the end-of-life tyres. In particular, the paper considers the
      properties of tyre waste and their potential reuse, the enhancement of end-of
      life tires and the various types of recovery, such as the reconstruction of tyres
      and the material recovery. The aspects related to the energy recovery and the use
      of the life cycle analysis, as a tool to support the choices of the best
      management system, were also taken into consideration, not forgetting that an
      adequate end-of-life planning is important when developing a sustainable product,
      since it can affect considerably its overall life cycle. 

PMID- 25943288
TI  - Emergency Physicians' Perceptions and Decision-making Processes Regarding
      Patients Presenting with Palpitations.
AB  - BACKGROUND: Palpitations are a common emergency department (ED) complaint, yet
      relatively little research exists on this topic from an emergency care
      perspective. OBJECTIVES: We sought to describe the perceptions and clinical
      decision-making processes of emergency physicians (EP) surrounding patients with
      palpitations. METHODS: We conducted 21 semistructured interviews with a
      convenience sample of EPs. We recruited participants from academic and community
      practice settings from four regions of the United States. The transcribed
      interviews were analyzed using a combination of structural coding and grounded
      theory approaches with ATLAS.ti, a qualitative data analysis software program
      (version 7; Atlas.ti Scientific Software Development GmbH, Berlin, Germany).
      RESULTS: EPs perceive palpitations to be a common but generally benign chief
      complaint. EPs' clinical approach to palpitations, with regards to testing,
      treatment, and ED management, can be classified as relating to one or more of the
      following themes: (1) risk stratification, (2) diagnostic categorization, (3)
      algorithmic management, and (4) case-specific gestalt. With regard to disposition
      decisions, four main themes emerged: (1) presence of a serious diagnosis, (2)
      perceived need for further cardiac testing/monitoring, (3) presence of key
      associated symptoms, (4) request of other physician or patient desire. The
      interrater reliability exercise yielded a Fleiss' kappa measure of 0.69,
      indicating substantial agreement between coders. CONCLUSION: EPs perceive
      palpitations to be a common but generally benign chief complaint. EPs rely on one
      or more of four main clinical approaches to manage these patients. These findings
      could help guide future efforts at developing risk-stratification tools and
      clinical algorithms for patients with palpitations.

PMID- 25943289
TI  - Subcapsular renal hematoma after ureteroscopy with holmium:yttrium-aluminum
      garnet laser lithotripsy.
AB  - Subcapsular renal hematoma (SRH) after ureteroscopic lithotripsy (URSL) using
      holmium:yttrium-aluminum-garnet (Ho:YAG) laser to treat ureteric stones is a rare
      complication. We aimed to review our unit's experience of post-URSL subcapsular
      renal hematoma. From 2006 to 2012, 2059 URSLs using F9.5 rigid ureteroscope were
      performed in our unit. Patients with post-URSL symptomatic renal hematoma were
      reviewed. Perioperative information on patients' renal function, stone
      characteristics, and degree of renal hydronephrosis were reviewed. Operative
      data, postoperative information such as clinical manifestation, changes in blood
      parameters, CT findings, and subsequent treatment were documented. Of the 2059
      patients treated with URSL and Ho:YAG laser, three patients were diagnosed as
      subcapsular renal hematoma after surgery; the age is 57, 61, and 63 years old,
      respectively. Preoperative imaging examination showed that two patients and one
      patient had obstructing middle and proximal ureteral stones ranging in size from
      0.8 to 1.6 cm, and three patients had thin renal cortices. The double-J ureteral
      stents were inserted in all cases regularly. All three subcapsular renal hematoma
      patients had the loin pain of the operation side and fever, and one patient had
      significant hemoglobin drop (from 111 to 61 g/L) who need to transfusion. Two
      patients presented within 24 h of URSL, and one patient presented on day 10. One
      patient was treated conservatively for 3 weeks and recovered with bed rest,
      antibiotics, hemostasis, and analgesia with no intervention or drain. The other
      two patients underwent ultrasonography-guided drainage of the hematoma. Two-month
      follow-up CT scans or ultrasonography confirmed the resolution of the hematoma in
      all three cases. Renal subcapsular hematoma after URSL is a rare and one of
      serious complications. Subcapsular renal hematoma should be considered when
      patients have the symptoms of significant loin pain after URSL for obstructing
      ureteral stones with thin renal cortices. The treatment of post-URSL renal
      subcapsular hematomas needs to be customized for each patient. 

PMID- 25943290
TI  - Mast cells in rheumatic disease.
AB  - Rheumatoid Arthritis is a chronic autoimmune disease with a complex disease
      pathogenesis leading to inflammation and destruction of synovial tissue in the
      joint. Several molecules lead to activation of immune pathways, including
      autoantibodies, Toll-Like Receptor ligands and cytokines. These pathways can
      cooperate to create the pro-inflammatory environment that results in tissue
      destruction. Each of these pathways can activate mast cells, inducing the release
      of a variety of inflammatory mediators, and in combination can markedly enhance
      mast cell responses. Mast cell-derived cytokines, chemokines, and proteases have
      the potential to induce recruitment of other leukocytes able to evoke tissue
      remodeling or destruction. Likewise, mast cells can secrete a plethora of factors
      that can contribute to tissue remodeling and fibroblast activation. Although the
      functional role of mast cells in arthritis pathogenesis in mice is not yet
      elucidated, the increased numbers of mast cells and mast cell-specific mediators
      in synovial tissue of rheumatoid arthritis patients suggest that mast cell
      activation in rheumatoid arthritis may contribute to its pathogenesis. 

PMID- 25943291
TI  - Epidemiology of occupational injuries by nationality in Qatar: Evidence for
      focused occupational safety programmes.
AB  - INTRODUCTION: Occupational injuries are the second leading cause of trauma
      admission in Qatar. Given the wide diversity of the country's migrant worker
      populations at risk, this study aimed to analyse and describe the epidemiology of
      these injuries based on the workers nationality residing in Qatar. METHODS: A
      retrospective analysis of trauma registry data on occupational-related injuries
      was conducted. The analysis included all patients [aged >=18 years] admitted to
      the Level I Hamad Trauma Center, from January 1, 2010 to December 31, 2013.
      RESULTS: Out of 6555 trauma admissions, 2015 (30.7%) patients had occupational
      injury. The admitted Case Fatality Rate (CFR) was 4.3 per 100 occupational injury
      related trauma admissions. Overall non-fatal occupational injury rate was 37.34
      per 100,000 workers, whereas fatal injury rate was 1.58 per 100,000 workers. Most
      of the workers experiencing occupational injuries were from Nepal (28%), India
      (20%) and Bangladesh (9%). Fatal occupational injuries were predominately among
      Indians (20%), Nepalese (19%), and Filipinos/Bangladeshis (both 8%). Filipinos
      had the highest admitted CFR at 8.2 deaths per 100 trauma admissions with the
      next highest being Indians and Indonesians (4.2 per 100 trauma admissions).
      During the study period, the incidence of severe occupational injuries decreased
      despite a simultaneous increase in the worker population within Qatar. Almost one
      in four occupational injuries was a major trauma (ISS>=16). Nepalese and Indian
      workers represented 29% and 18% of all major trauma cases. CONCLUSIONS: Non-fatal
      occupational injuries appear to follow a pattern distinct from fatal ones. High
      risk worker populations as defined by those with high admitted CFRs, experiencing
      the most severe or fatal injuries, must be the focus of targeted risk factor
      analysis and occupational safety interventions.

PMID- 25943292
TI  - Severe osteogenesis imperfecta Type-III and its challenging treatment in newborn
      and preschool children. A systematic review.
AB  - Osteogenesis imperfecta (OI) is a group of genetic disorders, of which Type III
      is the most severe among survivors. The disease is characterised in particular by
      bone fragility, decreased bone mass and increased incidence of fractures. Other
      usual findings are muscle hypotonia, joint hypermobility and short stature.
      Fractures and weak bones may consequently cause limb and spinal deformity and
      chronic physical disability. Bisphosphonates have revolutionised the treatment of
      newborn children with severe OI type III. Surgery is still needed in most
      patients due to high frequency of the fractures. In this systematic review we
      describe the present state-of-art in treating the most severe type of OI in
      newborn and preschool children with their bone fractures. 

PMID- 25943293
TI  - Admission fibrinogen levels in severe trauma patients: A comparison of elderly
      and younger patients.
AB  - INTRODUCTION: Acute coagulopathy of trauma has been much discussed recently.
      However, the changes in coagulation markers after trauma in the elderly are
      unknown. Furthermore, the baseline fibrinogen level is high in elderly patients,
      and the question remains as to whether fibrinogen levels also decrease early and
      the degree of decrease in elderly trauma patients. The purpose of this study was
      to compare coagulation markers including the fibrinogen level on admission in
      younger and elderly severe trauma patients. METHODS: A cohort of severe trauma
      patients (Injury Severity Score (ISS) >=16), admitted from January 2011 to June
      2014, with coagulation markers including the fibrinogen level on admission
      available, was reviewed retrospectively. The patients were divided into a younger
      (16-64 years old) and an older (>=65 years old) group based upon their age at
      presentation. Activated partial thromboplastin time (aPTT), international
      normalized ratio (INR), fibrinogen, and D-dimer were compared between the younger
      and older groups. RESULTS: There were 251 patients who met the inclusion criteria
      for this analysis. The younger group included 117 patients and the older group
      included 134 patients. The median aPTT (26.3 vs 27.5s, P=0.001) and median D
      dimer levels (18.8 vs 40.2 MUg/dL, P=0.006) were significantly higher in the
      older group. However, the fibrinogen level (205 vs 248 mg/dL, P<0.001) was
      significantly higher in the older group. The regression lines of fibrinogen and
      age in non-massive transfusion and massive transfusion cases are given by Y=1.03
      X+185 (r=0.24, r(2)=0.06, P<0.001) and Y=0.86 X+134 (r=0.25, r(2)=0.06, P=0.09)
      respectively, and the fibrinogen levels tended to increase with older age in
      severe trauma patients. CONCLUSIONS: The fibrinogen level did not show a low
      value as it can in younger patients in elderly patients. Therefore, the
      fibrinogen level is difficult to use as an early indicator of acute blood loss
      with haemorrhage in elderly severe trauma patients, as it can be used in younger
      patients. Thus, it is necessary to keep in mind that the fibrinogen level
      increases by approximately 1mg/dL when the age increases by 1 year and to
      carefully observe the fibrinogen level even if the admission level is not low.

PMID- 25943294
TI  - Successful reimplantation of extruded long bone segments in open fractures of
      lower limb--a report of 3 cases.
AB  - Extruded bone segments are rare complication of high energy open fractures.
      Routinely these fractures are treated by debridement followed by bone loss
      management in the form of either bone transport or free fibula transfer. There
      are very few reports in the literature about reimplantation of extruded segments
      of bone and there are no clear guidelines regarding timing of reimplantation,
      bone stabilisation and sterilisation techniques. Reimplantation of extruded bone
      is a risky procedure due to high chances of infection which determines the final
      outcome and can result in secondary amputations. We present two cases of
      successful reimplantation of extruded diaphyseal segment of femur and one case of
      reimplantation of extruded segment of tibia.

PMID- 25943295
TI  - Electromagnetic Sensor-Guided Enteral Access Systems: A Literature Review.
AB  - Enteral feeding is the nutritional support of choice for acutely ill patients
      with functional gastrointestinal tracts who are unable to swallow. Several
      benefits including reduced mortality and length of hospital stay have been
      associated with early initiation of enteral feeding. However, misplacement of
      conventional nasoenteric tubes is relatively common and can result in
      complications including pneumothorax. In addition, the need to confirm the
      position by X-ray can delay the start of using the tube. Eliminating these delays
      can help patients start feeding, and minimise the adverse impact on initiating
      hydration and medication. The purpose of this review was to critically examine
      whether electromagnetic sensor-guided enteral access systems (EMS-EAS) can help
      overcome the challenges of conventional nasoenteric feeding tube placement and
      confirmation. The Royal Society of Medicine's library performed two searches on
      Medline (1946-March 2014) and Embase (1947-March 2014) covering all papers on
      Cortrak or electromagnetic or magnetic guidance systems for feeding tubes in
      adults. Results from the literature search found an agreement between the
      radiographic and EMS-EAS confirmation of placement. EMS-EAS virtually eliminated
      the risk of misplacement and pneumothorax was not reported. In addition, studies
      showed a small decrease in the number of X-rays with EMS-EAS and a reduced
      average time to start feeding compared with blind placement. This review suggests
      that EMS-EAS reduces several complications associated with the misplacement of
      nasoenteric feeding tubes, and that there could be considerable improvements in
      mortality, morbidity, patient experience and cost if EMS-EAS is used instead of
      conventional methods. 

PMID- 25943296
TI  - Penetration-Aspiration: Is Their Detection in FEES (r) Reliable Without Video
      Recording?
AB  - Penetration-aspiration is known as the main finding in deglutition-disordered
      patients with implications for diagnostics and therapeutic management. Reliable
      detection of penetration-aspiration is given with fiberoptic endoscopic
      evaluation of swallowing (FEES((r))) as one of the gold standards in instrumental
      swallowing evaluation. The advice to implement video recording in FEES((r)) to
      assure quality in identifying penetration-aspiration is often ignored, especially
      in bed-side settings. Thus, the aim of this study was to compare reliability and
      validity in detecting penetration-aspiration events with and without video
      recording. Eighty FEES((r)) sequences, ten per severity grade of the Penetration
      Aspiration Scale by Rosenbek et al., were rated by four blinded ENTs with two
      different methods. The first method simulated the evaluation without video
      recording (Method A), and the second one with video recording (Method B). Rating
      was performed twice per setting with 2 weeks in between and every time newly
      randomized. Intra- and inter-rater reliability as well as validity were analyzed
      for both evaluation methods. R-to-Z transformation was used to reveal the more
      reliable method and ordinal regression to determine potential rating influences.
      Method B demonstrated higher intra- and inter-rater reliability values than
      Method A and was revealed as more reliable in identifying penetration-aspiration
      according to r-to-Z transformation (Z = -2.92, p = .004). Ordinal regression
      detected a significant influence of the evaluation method choice on the rating
      results (p = .016). As Method B turned out to be more reliable than Method A in
      detecting penetration-aspiration, the presented study recommends the
      implementation of video recording in swallowing diagnostics.

PMID- 25943297
TI  - Chronic toxicity of the antiepileptic carbamazepine on the clam Ruditapes
      philippinarum.
AB  - The impacts of carbamazepine (CBZ) on aquatic organisms are yet not well
      investigated. The present study aimed to better understand the chronic effects of
      environmentally relevant concentrations of CBZ. The experiment was performed by
      exposing the filter feeding clam Ruditapes philippinarum to 0.00, 0.03, 0.30,
      3.00 and 9.00MUg/L, during 28days. To assess the chronic toxicity of the drug a
      battery of biomarkers related with health status and oxidative stress was
      applied. In order to quantify CBZ in the clam's tissues and in water samples
      ELISA was used. The present study showed three types of responses on the clams
      after a chronic exposure to CBZ. For control condition and the lower
      concentrations (0.03 and 0.30MUg/L) a "similar" metabolic state was observed and
      the most efficient antioxidant status leading to the elimination of reactive
      oxygen species formed during the metabolism of CBZ. The concentration of
      3.00MUg/L seemed to be a "threshold" concentration, beyond which the
      concentration levels of CBZ began to exert a toxic effect, compromising the
      activity of biotransformation and antioxidant enzymes, with notorious effects at
      the highest CBZ concentration (9.00MUg/L). CBZ also seemed to alter the energy
      related responses, especially the glycogen and electron system responses,
      revealing a slowdown in metabolism at the higher exposure concentrations (3.00
      and 9.00MUg/L). Overall, the present study demonstrated that the higher CBZ
      concentrations can lead to the impairment of antioxidant enzymes compromising the
      neutralization of reactive oxygen species, and thus the ability to cope with
      oxidative stress. 

PMID- 25943298
TI  - Atmospheric N deposition alters connectance, but not functional potential among
      saprotrophic bacterial communities.
AB  - The use of co-occurrence patterns to investigate interactions between micro
      organisms has provided novel insight into organismal interactions within
      microbial communities. However, anthropogenic impacts on microbial co-occurrence
      patterns and ecosystem function remain an important gap in our ecological
      knowledge. In a northern hardwood forest ecosystem located in Michigan, USA, 20
      years of experimentally increased atmospheric N deposition has reduced forest
      floor decay and increased soil C storage. This ecosystem-level response occurred
      concomitantly with compositional changes in saprophytic fungi and bacteria. Here,
      we investigated the influence of experimental N deposition on biotic interactions
      among forest floor bacterial assemblages by employing phylogenetic and molecular
      ecological network analysis. When compared to the ambient treatment, the forest
      floor bacterial community under experimental N deposition was less rich, more
      phylogenetically dispersed and exhibited a more clustered co-occurrence network
      topology. Together, our observations reveal the presence of increased biotic
      interactions among saprotrophic bacterial assemblages under future rates of N
      deposition. Moreover, they support the hypothesis that nearly two decades of
      experimental N deposition can modify the organization of microbial communities
      and provide further insight into why anthropogenic N deposition has reduced
      decomposition, increased soil C storage and accelerated phenolic DOC production
      in our field experiment.

PMID- 25943299
TI  - Transmission of Hepatitis C Virus From Organ Donors Despite Nucleic Acid Test
      Screening.
AB  - Nucleic acid testing (NAT) for hepatitis C virus (HCV) is recommended for
      screening of organ donors, yet not all donor infections may be detected. We
      describe three US clusters of HCV transmission from donors at increased risk for
      HCV infection. Donor's and recipients' medical records were reviewed. Newly
      infected recipients were interviewed. Donor-derived HCV infection was considered
      when infection was newly detected after transplantation in recipients of organs
      from increased risk donors. Stored donor sera and tissue samples were tested for
      HCV RNA with high-sensitivity quantitative PCR. Posttransplant and pretransplant
      recipient sera were tested for HCV RNA. Quasispecies analysis of hypervariable
      region-1 was used to establish genetic relatedness of recipient HCV variants.
      Each donor had evidence of injection drug use preceding death. Of 12 recipients,
      8 were HCV-infected-6 were newly diagnosed posttransplant. HCV RNA was
      retrospectively detected in stored samples from donor immunologic tissue
      collected at organ procurement. Phylogenetic analysis showed two clusters of
      closely related HCV variants from recipients. These investigations identified the
      first known HCV transmissions from increased risk organ donors with negative NAT
      screening, indicating very recent donor infection. Recipient informed consent and
      posttransplant screening for blood-borne pathogens are essential when considering
      increased risk donors. 

PMID- 25943300
TI  - Acute and chronic pseudo-obstruction: a current update.
AB  - Acute colonic pseudo-obstruction (ACPO) and chronic intestinal pseudo-obstruction
      (CIPO) are distinct clinical entities in which patients present similarly with
      symptoms of a mechanical obstruction without an occlusive lesion. Unfortunately,
      they also share the issues related to a delay in diagnosis, including
      inappropriate management and poor outcomes. Advancements have been made in our
      understanding of the aetiologies of both conditions. Several predisposing factors
      linked to critical illness have been implicated in ACPO. CIPO is a functional
      motility disorder, historically misdiagnosed, with unnecessary surgery being
      performed in many patients with dire consequences. This review discusses the
      pathophysiology, clinical and diagnostic features, and treatment of each. For
      ACPO, a safer pharmacological approach to treatment is presented in a modified up
      to-date algorithm. The importance of CIPO as a differential diagnosis when seeing
      patients with recurrent admissions for abdominal pain and distention is also
      discussed, as well as specific indications for surgery. While surgery is often a
      last resort, the role of the surgeon in the management of both ACPO and CIPO
      cannot be undervalued. By characterizing each condition in a common review, the
      knowledge gleaned aims to optimize outcomes for these frequently complex
      patients. 

PMID- 25943301
TI  - The natural yeast extract isolated by ethanol precipitation inhibits melanin
      synthesis by modulating tyrosinase activity and downregulating melanosome
      transfer.
AB  - This study was conducted to examine the effects of EP-2, a natural yeast extract
      isolated by ethanol precipitation from Saccharomyces cerevisiae, on melanogenesis
      and to determine its underlying mechanism of action. Our results show that
      although EP-2 is not a direct tyrosinase inhibitor, when EP-2 was added to the
      culture media of B16F10 melanoma cells, intracellular tyrosinase activity was
      decreased. However, EP-2 had no effect on the expression of microphthalmia
      associated transcription factor or tyrosinase. EP-2 was found to inhibit
      melanogenesis and melanosome transfer when it was added to melanocytes and
      keratinocytes in coculture. In addition, protease-activated receptor 2, a key
      protein associated with melanosome transfer from melanocytes to keratinocytes,
      was downregulated in the presence of EP-2. In conclusion, EP-2 is a potent
      inhibitor of melanogenesis and its hypomelanogenic effect is related to the
      inhibition of tyrosinase activity and transfer of melanosomes. 

PMID- 25943302
TI  - Cross-Linguistic Differences in Processing Double-Embedded Relative Clauses:
      Working-Memory Constraints or Language Statistics?
AB  - An English double-embedded relative clause from which the middle verb is omitted
      can often be processed more easily than its grammatical counterpart, a phenomenon
      known as the grammaticality illusion. This effect has been found to be reversed
      in German, suggesting that the illusion is language specific rather than a
      consequence of universal working memory constraints. We present results from
      three self-paced reading experiments which show that Dutch native speakers also
      do not show the grammaticality illusion in Dutch, whereas both German and Dutch
      native speakers do show the illusion when reading English sentences. These
      findings provide evidence against working memory constraints as an explanation
      for the observed effect in English. We propose an alternative account based on
      the statistical patterns of the languages involved. In support of this
      alternative, a single recurrent neural network model that is trained on both
      Dutch and English sentences is shown to predict the cross-linguistic difference
      in the grammaticality effect. 

PMID- 25943303
TI  - Micro-anatomical characterization of vertebral curvatures in Senegalese sole
      Solea senegalensis.
AB  - The micro-anatomical changes associated with lordotic and kyphotic vertebral
      curvatures (VC) in juvenile and adult Senegalese sole Solea senegalensis are
      described. In addition, it is demonstrated that the tissue and cellular
      structures of individual vertebrae can be severely affected. Two main
      conformations were found in deformed juvenile specimens: flattened vertebrae with
      dorso-ventral compression and trapezoidal vertebrae forming concave and convex
      sides under compressive and tensile stresses. Histological analyses revealed the
      occurrence of an ectopic cartilaginous tissue within the acellular bone, both in
      juveniles and adults, possibly to cope with altered mechanical stress in deformed
      vertebrae. The results suggest that the alteration in loading to which curved
      vertebral columns are subjected might trigger vertebral reshaping and
      differentiation of cells towards this ectopic tissue. In addition, mesenchymal
      cells appear to play an important role in its formation. It is here proposed that
      the acellular bone of S. senegalensis is capable of adaptively responding to
      altered loading regimes at the structural level by reshaping vertebrae and at the
      micro-anatomical level by recruiting chondrocyte-like cells to areas of altered
      mechanical stress. 

PMID- 25943304
TI  - Effects of High-Hydrostatic Pressure on Inactivation of Human Norovirus and
      Physical and Sensory Characteristics of Oysters.
AB  - The purpose of the study was to determine the effect of high-hydrostatic pressure
      (HHP) on inactivation of human norovirus (HuNoV) in oysters and to evaluate
      organoleptic characteristics of oysters treated at pressure levels required for
      HuNoV inactivation. Genogroup I.1 (GI.1) or Genogroup II.4 (GII.4) HuNoV was
      inoculated into oysters and treated at 300 to 600 MPa at 25 and 0  degrees C for
      2 min. After HHP, viral particles were extracted by porcine gastric mucin
      conjugated magnetic beads (PGM-MBs) and viral RNA was quantified by real-time RT
      PCR. Lower initial temperature (0  degrees C) significantly enhanced HHP
      inactivation of HuNoV compared to ambient temperature (25  degrees C; P < 0.05).
      HHP at 350 and 500 MPa at 0  degrees C could achieve more than 4 log10 reduction
      of GII.4 and GI.1 HuNoV in oysters, respectively. HHP treatments did not
      significantly change color or texture of oyster tissue. A 1- to 5-scale hedonic
      sensory evaluation on appearance, aroma, color, and overall acceptability showed
      that pressure-treated oysters received significantly higher quality scores than
      the untreated control (P < 0.05). Elevated pressure levels at 450 and 500 MPa did
      not significantly affect scores compared to 300 MPa at 0  degrees C, indicating
      increasing pressure level did not affect sensory acceptability of oysters.
      Oysters treated at 0  degrees C had slightly lower acceptability than the group
      treated at room temperature on day 1 (P < 0.05), but after 1 wk storage, no
      significant difference in sensory attributes and consumer desirability was
      observed (P > 0.05). 

PMID- 25943305
TI  - Food safety considerations for innovative nutrition solutions.
AB  - Failure to secure safe and affordable food to the growing global population leads
      far too often to disastrous consequences. Among specialists and other
      individuals, food scientists have a key responsibility to improve and use science
      based tools to address risk and advise food handlers and manufacturers with best
      practice recommendations. With collaboration from production agriculture, food
      processors, state and federal agencies, and consumers, it is critical to
      implement science-based strategies that address food safety and that have been
      evaluated for effectiveness in controlling and/or eliminating hazards. It is an
      open question whether future food safety concerns will shift in priority given
      the imperatives to supply sufficient food. This report brings together leading
      food safety experts to address these issues with a focus on three areas:
      economic, social, and policy aspects of food safety; production and postharvest
      technology for safe food; and innovative public communication for food safety and
      nutrition. 

PMID- 25943308
TI  - Abscisic acid deficiency increases defence responses against Myzus persicae in
      Arabidopsis.
AB  - Comparison of Arabidopsis thaliana (Arabidopsis) gene expression induced by Myzus
      persicae (green peach aphid) feeding, aphid saliva infiltration and abscisic acid
      (ABA) treatment showed a significant positive correlation. In particular, ABA
      regulated genes are over-represented among genes that are induced by M. persicae
      saliva infiltration into Arabidopsis leaves. This suggests that the induction of
      ABA-related gene expression could be an important component of the Arabidopsis
      aphid interaction. Consistent with this hypothesis, M. persicae populations
      induced ABA production in wild-type plants. Furthermore, aphid populations were
      smaller on Arabidopsis aba1-1 mutants, which cannot synthesize ABA, and showed a
      significant preference for wild-type plants compared with the mutant. Total free
      amino acids, which play an important role in aphid nutrition, were not altered in
      the aba1-1 mutant line, but the levels of isoleucine (Ile) and tryptophan (Trp)
      were differentially affected by aphids in wild-type and mutant plants. Recently,
      indole glucosinolates have been shown to promote aphid resistance in Arabidopsis.
      In this study, 4-methoxyindol-3-ylmethylglucosinolate was more abundant in the
      aba1-1 mutant than in wild-type Arabidopsis, suggesting that the induction of ABA
      signals that decrease the accumulation of defence compounds may be beneficial for
      aphids. 

PMID- 25943309
TI  - A cis-acting antitoxin domain within the chromosomal toxin-antitoxin module EzeT
      of Escherichia coli quenches toxin activity.
AB  - Toxin-antitoxin (TA) systems are widespread genetic modules in the genomes of
      bacteria and archaea emerging as key players that modulate bacterial physiology.
      They consist of two parts, a toxic component that blocks an essential cellular
      process and an antitoxin that inhibits this toxic activity during normal growth.
      According to the nature of the antitoxin and the mode of inhibition, TA systems
      are subdivided into different types. Here, we describe the characterization of a
      type II-like TA system in Escherichia coli called EzeT. While in conventional
      type II systems the antitoxin is expressed in trans to form an inactive protein
      protein complex, EzeT consists of two domains combining toxin and cis-acting
      antitoxin functionalities in a single polypeptide chain. We show that the C
      terminal domain of EzeT is homologous to zeta toxins and is toxic in vivo. The
      lytic phenotype could be attributed to UDP-N-acetylglucosamine phosphorylation,
      so far only described for type II epsilon/zeta systems from Gram-positive
      streptococci. Presence of the N-terminal domain inhibits toxicity in vivo and
      strongly attenuates kinase activity. Autoinhibition by a cis-acting antitoxin as
      described here for EzeT-type TA systems can explain the occurrence of single or
      unusually large toxins, further expanding our understanding of the TA system
      network. 

PMID- 25943307
TI  - Adaptation to antiangiogenic therapy in neurological tumors.
AB  - Because tumors require a vascular supply for their survival and growth,
      angiogenesis is considered an important therapeutic target in most human cancers
      including cancer of the central nervous system. Antiangiogenic therapy has
      focused on inhibitors of the vascular endothelial growth factor (VEGF) signaling
      pathway. VEGF pathway-targeted drugs have shown therapeutic efficacy in several
      CNS tumors and have been tried most frequently in glioblastoma. These therapies,
      however, have been less effective than anticipated as some patients do not
      respond to therapy and some receive only modest benefit. Underlying this
      suboptimal response are multiple mechanisms of drug resistance involving changes
      in both tumor cells and their microenvironment. In this review, we discuss the
      multiple proposed mechanisms by which neurological tumors evolve to become
      resistant to antiangiogenic therapies. A better understanding of these
      mechanisms, their context, and their interplay will likely facilitate
      improvements in pharmacological strategies for the targeted treatment of
      neurological tumors. 

PMID- 25943306
TI  - Physiological, pathological, and structural implications of non-enzymatic protein
      protein interactions of the multifunctional human transglutaminase 2.
AB  - Transglutaminase 2 (TG2) is a ubiquitously expressed member of an enzyme family
      catalyzing Ca(2+)-dependent transamidation of proteins. It is a multifunctional
      protein having several well-defined enzymatic (GTP binding and hydrolysis,
      protein disulfide isomerase, and protein kinase activities) and non-enzymatic
      (multiple interactions in protein scaffolds) functions. Unlike its enzymatic
      interactions, the significance of TG2's non-enzymatic regulation of its
      activities has recently gained importance. In this review, we summarize all the
      partners that directly interact with TG2 in a non-enzymatic manner and analyze
      how these interactions could modulate the crosslinking activity and cellular
      functions of TG2 in different cell compartments. We have found that TG2 mostly
      acts as a scaffold to bridge various proteins, leading to different functional
      outcomes. We have also studied how specific structural features, such as
      intrinsically disordered regions and embedded short linear motifs contribute to
      multifunctionality of TG2. Conformational diversity of intrinsically disordered
      regions enables them to interact with multiple partners, which can result in
      different biological outcomes. Indeed, ID regions in TG2 were identified in
      functionally relevant locations, indicating that they could facilitate
      conformational transitions towards the catalytically competent form. We reason
      that these structural features contribute to modulating the physiological and
      pathological functions of TG2 and could provide a new direction for detecting
      unique regulatory partners. Additionally, we have assembled all known anti-TG2
      antibodies and have discussed their significance as a toolbox for identifying and
      confirming novel TG2 regulatory functions. 

PMID- 25943312
TI  - First-episode psychosis in the criminal justice system: identifying a critical
      intercept for early intervention.
AB  - LEARNING OBJECTIVE: After participating in this activity, learners should be
      better able to:Evaluate emerging concepts of identification, treatment and
      discharge planning for individuals who are experiencing a first psychotic episode
      while detained in the criminal justice system. ABSTRACT: The United States
      incarcerates more people than any other nation in the world. The system of jails
      and prisons that holds those individuals has become the largest provider of
      mental health care in the country, with rates of psychotic illness many times
      higher than in the community. A subset of this population includes individuals
      experiencing their first episode of psychosis who are untreated and are new to
      the rules of institutional settings. Retrospective and anecdotal reports indicate
      that many individuals in the criminal justice system have first-episode
      psychosis, yet no published information is available about the actual rates. For
      these patients, behavior associated with psychotic symptoms may have led to their
      arrest, but correctional facilities are poorly equipped to identify their needs
      and to provide the type of comprehensive treatment needed to improve functional
      status, quality of life, and illness recovery. Even as first-episode programs are
      flourishing in community settings, we know little about how to identify, engage,
      possibly divert, and treat these patients in settings designed as punishment.
      Efforts should be made both to reduce the number of these individuals
      inappropriately prosecuted within the criminal justice system and to begin in
      jail efforts to engage them in treatment, in anticipation of their eventual
      return to the community.

PMID- 25943310
TI  - Patient and health care professional decision-making to commence and withdraw
      from renal dialysis: a systematic review of qualitative research.
AB  - BACKGROUND AND OBJECTIVE: To ensure that decisions to start and stop dialysis in
      ESRD are shared, the factors that affect patients and health care professionals
      in making such decisions must be understood. This systematic review sought to
      explore how and why different factors mediate the choices about dialysis
      treatment. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: MEDLINE, Embase,
      CINAHL, and PsychINFO were searched for qualitative studies of factors that
      affect patients' or health care professionals' decisions to commence or withdraw
      from dialysis. A thematic synthesis was conducted. RESULTS: Of 494 articles
      screened, 12 studies (conducted from 1985 to 2014) were included. These involved
      206 patients (most receiving hemodialysis) and 64 health care professionals (age
      ranges: patients, 26-93 years; professionals, 26-61 years). For commencing
      dialysis, patients based their choice on "gut instinct," as well as deliberating
      over the effect of treatment on quality of life and survival. How individuals
      coped with decision-making was influential: Some tried to take control of the
      problem of progressive renal failure, whereas others focused on controlling their
      emotions. Health care professionals weighed biomedical factors and were led by an
      instinct to prolong life. Both patients and health care professionals described
      feeling powerless. With regard to dialysis withdrawal, only after prolonged
      periods on dialysis were the realities of life on dialysis fully appreciated and
      past choices questioned. By this stage, however, patients were physically
      dependent on treatment. As was seen with commencing dialysis, individuals coped
      with treatment withdrawal in a problem- or emotion-controlling way. Families
      struggled to differentiate between choosing versus allowing death. Health care
      teams avoided and queried discussions regarding dialysis withdrawal. Patients,
      however, missed the dialogue they experienced during predialysis education.
      CONCLUSIONS: Decision-making in ESRD is complex and dynamic and evolves over time
      and toward death. The factors at work are multifaceted and operate differently
      for patients and health professionals. More training and research on open
      communication and shared decision-making are needed.

PMID- 25943311
TI  - The androgen receptor plays a suppressive role in epithelial- mesenchymal
      transition of human prostate cancer stem progenitor cells.
AB  - BACKGROUND: To investigate the roles of androgen receptor (AR) in epithelial-
      mesenchymal transition (EMT) in human prostate cancer stem progenitor (S/P) cells
      isolated from LNCaP cell line. METHODS: The S/P cells were obtained from LNCaP
      cell line through florescence-activated cell sorting (FACS). AR was overexpressed
      in S/P cells through lentivirus. Western blot assay was used to detect the EMT
      markers expression, such as E Cadherin, N Cadherin, Vimentin and Snail. MTT
      assay, soft agar colony formation assay, sphere formation assay and migration
      assay were used to investigate AR's roles in EMT of S/P cells. Cell signaling
      pathways associated with proliferation and apoptosis of S/P cells were detected
      simultaneously. And S/P cells were treated with in vitro combinatory use of LY
      294002 (inhibitor of AKT signaling molecules) with gamma-TT and/or 5-AZA.
      RESULTS: Our data showed that S/P cells from LNCaP had high EMT markers
      expression, more tumorigenesis and strong migration ability. And in S/P cells
      overexpressed with AR, the expression of EMT markers decreased. In addition,
      these cells had less proliferation ability, tumorigenesis ability, self-renewal
      and migration ability. At the same time, targeting S/P cells with AKT signaling
      pathway inhibitor LY29004 and gamma-TT and/or 5-AZA could inhibit S/P cell's
      proliferation and tumorigenesis. CONCLUSIONS: Our data suggest that AR played a
      negative role in EMT of PCa S/P cells, by regulating AKT cell signaling pathway,
      which could be a new strategy to treat castration resistant prostate cancer
      (CRPC).

PMID- 25943313
TI  - Psychiatry department response to the Boston Marathon bombings within a level-1
      trauma center.
AB  - In this article we present how the consultation-liaison and psychology divisions
      of an academic medical center's Department of Psychiatry responded in the first
      week after the Boston Marathon bombings, specifically in the context of disaster
      response guidelines and evidence-based approaches to acute trauma. Since the
      department had to address several complicated matters at multiple levels within
      the hospital system, we highlight unexpected issues unique to this particular
      event as they arose within the primary domains of our involvement. This article
      aims to (1) provide a descriptive analysis of how we enacted disaster and trauma
      guidelines and evidence-based care within a hospital setting, (2) shed light on
      the unique and unexpected administrative and systemic issues encountered in our
      response, and (3) discuss lessons learned, including opportunities to improve
      trauma-related care. 

PMID- 25943314
TI  - Building bridges in a fractured family: developing new conversations around
      technology and sexual orientation.

PMID- 25943315
TI  - Epigenetic mechanisms in the pathophysiology of psychotic disorders.
AB  - Epigenetics is the study of chromatin-the physical material that forms
      chromosomes, composed of DNA wound around specialized histone proteins-and of how
      the modification of chromatin acts to establish stable states of gene expression
      in a cell-specific manner. Chromatin is regulated through three mechanisms: DNA
      methylation, histone modification, and RNA interference. These basic biological
      processes form the molecular interface between the genome and the environment,
      contributing to the regulation of gene expression in health and disease.
      Investigation of epigenetic mechanisms is yielding exciting insights in many
      areas of medicine, and a large and rapidly growing literature describes
      epigenetics as central to many aspects of the pathophysiology of psychotic
      disorders. This article first discusses speculative points as to why the
      mechanisms of epigenetics may be satisfying explanatory mechanisms in the
      etiology of psychotic disorders, then details emerging experimental evidence of
      roles for the three types of epigenetic mechanisms in these illnesses, and
      finally discusses these mechanisms as potentially compelling areas of research
      for the development of future treatments.

PMID- 25943317
TI  - Patch time allocation and oviposition behavior in response to patch quality and
      the presence of a generalist predator in Meteorus pulchricornis (Hymenoptera:
      Braconidae).
AB  - Foraging parasitoids often must estimate local risk of predation just as they
      must estimate local patch value. Here, we investigate the effects a generalist
      predator Chlaenius bioculatus (Coleoptera: Carabidae), has on the oviposition
      behavior and the patch residence decisions of a solitary parasitoid Meteorus
      pulchricornis (Hymenoptera: Braconidae) in response to the varying host quality
      of Spodoptera litura (Lepidoptera: Noctuidae) larvae (L2 and L4). M.
      pulchricornis attacked more L4 than on L2 hosts, with the difference in attack
      rate varying depending on predation treatments, greater in the presence (either
      actively feeding or not) of the predator than in the absence of it. The
      parasitoid attacked fewer L2 and L4 hosts when the predator was actively feeding
      than when it was not feeding or not present in the patch. M. pulchricornis
      decreased the patch leaving tendency with increasing rejections of hosts, but
      increased the tendency in response to the presence of the predator as compared
      with the absence of it, and furthermore, increased the patch leaving tendency
      when the predator was actively feeding as compared with when it was not. Our
      study suggests that M. pulchricornis can exploit high quality patches while
      minimizing predation risk, by attacking more hosts in high quality patches while
      reducing total patch time in response to risk of predation. 

PMID- 25943316
TI  - Transcriptome assembly, profiling and differential gene expression analysis of
      the halophyte Suaeda fruticosa provides insights into salt tolerance.
AB  - BACKGROUND: Improvement of crop production is needed to feed the growing world
      population as the amount and quality of agricultural land decreases and soil
      salinity increases. This has stimulated research on salt tolerance in plants.
      Most crops tolerate a limited amount of salt to survive and produce biomass,
      while halophytes (salt-tolerant plants) have the ability to grow with saline
      water utilizing specific biochemical mechanisms. However, little is known about
      the genes involved in salt tolerance. We have characterized the transcriptome of
      Suaeda fruticosa, a halophyte that has the ability to sequester salts in its
      leaves. Suaeda fruticosa is an annual shrub in the family Chenopodiaceae found in
      coastal and inland regions of Pakistan and Mediterranean shores. This plant is an
      obligate halophyte that grows optimally from 200-400 mM NaCl and can grow at up
      to 1000 mM NaCl. High throughput sequencing technology was performed to provide
      understanding of genes involved in the salt tolerance mechanism. De novo assembly
      of the transcriptome and analysis has allowed identification of differentially
      expressed and unique genes present in this non-conventional crop. RESULTS: Twelve
      sequencing libraries prepared from control (0 mM NaCl treated) and optimum (300
      mM NaCl treated) plants were sequenced using Illumina Hiseq 2000 to investigate
      differential gene expression between shoots and roots of Suaeda fruticosa. The
      transcriptome was assembled de novo using Velvet and Oases k-45 and clustered
      using CDHIT-EST. There are 54,526 unigenes; among these 475 genes are
      downregulated and 44 are upregulated when samples from plants grown under optimal
      salt are compared with those grown without salt. BLAST analysis identified the
      differentially expressed genes, which were categorized in gene ontology terms and
      their pathways. CONCLUSIONS: This work has identified potential genes involved in
      salt tolerance in Suaeda fruticosa, and has provided an outline of tools to use
      for de novo transcriptome analysis. The assemblies that were used provide
      coverage of a considerable proportion of the transcriptome, which allows analysis
      of differential gene expression and identification of genes that may be involved
      in salt tolerance. The transcriptome may serve as a reference sequence for study
      of other succulent halophytes.

PMID- 25943318
TI  - A Study on Unsafe Abortion Presented for Medicolegal Examination: Medicolegal
      Evidence and Limitations in Opinion.
AB  - INTRODUCTION: Unsafe abortion is a major health problem causing women's health at
      risk. It is the third leading cause of maternal mortality in Sri Lanka during the
      last decade. Strong evidence for administration of justice and thereby to improve
      the health care and policies regarding such victims is the expected aim of
      medicolegal examination. OBJECTIVE: The aims of the study were to determine the
      pattern of unsafe abortions in medicolegally referred cases and to assess the
      strengths and the limitations of medicolegal opinion in such cases. STUDY DESIGN:
      Retrospective descriptive study was done based on the notes of the medicolegal
      examinations performed by the authors, on women who underwent illegal abortions
      during past 5 years. RESULTS: Of 51 cases reviewed, mechanical interference was
      the method used in 45% of cases. Sixty-eight percent of the women were admitted
      to hospital with heavy bleeding. The condition on admission was critical
      requiring medical interventions to save the life in 53% of cases. Referral for
      medicolegal examination had been performed after 3 days of admission in the
      majority (59%) of cases, whereas in 47% of cases, there was a therapeutic
      interference within 3 days of medicolegal examination. At the time of medicolegal
      examination, evidence of initial interference could not be identified in majority
      (84%). CONCLUSION: Provision of strong evidence to give expected legal outcome in
      cases of illegal abortion is limited. Judiciary and law enforcement authorities
      should be aware of these limitations and look for strong corroborative evidence
      to implement the penalty.

PMID- 25943319
TI  - Epidermal Growth Factor Receptor Mutation Status in the Treatment of Non-small
      Cell Lung Cancer: Lessons Learned.
AB  - Advances in oncology research have led to identification of tumor-specific
      biomarkers, some of which are important predictive indicators and ideal targets
      for novel therapeutics. One such biomarker in non-small cell lung cancer (NSCLC)
      is the epidermal growth factor receptor (EGFR). Patients with NSCLC who harbor an
      activating EGFR mutation show a more favorable response to treatment with an EGFR
      inhibitor, such as gefitinib, erlotinib, or afatinib, than to chemotherapy. The
      prevalence of EGFR mutations in East Asian patients is higher than that in other
      populations, and in some clinical settings, patients have been treated with EGFR
      inhibitors based on clinicopathologic characteristics with no information on EGFR
      status. However, based on results from a series of studies in which East Asian
      patients with advanced non-squamous NSCLC were treated with EGFR inhibitors alone
      or in combination with standard chemotherapy, this may not be the best practice
      because EGFR mutation status was found to be a key predictor of outcome. Data
      from these studies highlight the necessity of EGFR testing in determining the
      most suitable treatment for patients with advanced or metastatic NSCLC. 

PMID- 25943320
TI  - Consequences of Incomplete Smoke-Free Legislation in the Republic of Korea:
      Results from Environmental and Biochemical Monitoring: Community Based Study.
AB  - PURPOSE: In some countries with high smoking prevalence, smoke-free legislation
      has only been implemented in specific public places, as opposed to a
      comprehensive ban on smoking in all public places. The purpose of this study was
      to provide valid data on second-hand smoke (SHS) exposure that reflect the
      consequences of incomplete smoke-free legislation, and provide a rationale for
      expanding this legislation. MATERIALS AND METHODS: Indoor and outdoor
      environmental exposure (fine particulate matter [PM2.5], air nicotine, and dust 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone [NNK]) was monitored in 35 public
      places where smoking is prohibited by law in Goyang, Republic of Korea.
      Biomarkers of SHS exposure (urinary cotinine, hair nicotine, and urinary 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanol) were measured in 37 non-smoking
      employees. Geometric means and standard deviations were used in comparison of
      each measure. RESULTS: Considerable exposure of SHS was detected at all indoor
      monitoring sites (PM2.5, 95.5 MUg/m(3) in private educational institutions; air
      nicotine, 0.77 MUg/m(3) in large buildings; and dust NNK, 160.3 pg/mg in large
      buildings); environmental measures were higher in private or closed locations,
      such as restrooms. Outdoor measures of SHS exposure were lowest in nurseries and
      highest in government buildings. Biochemical measures revealed a pattern of SHS
      exposure by monitoring site, and were highest in private educational
      institutions. CONCLUSION: The evidence of SHS exposure in legislative smoke-free
      places in Korea suggests that incomplete smoke free legislation and lack of
      enforcement of it might not protect people from exposure to smoke. Therefore,
      active steps should be taken toward a comprehensive ban on smoking in all public
      places and its enforcement.

PMID- 25943321
TI  - p16 Hypermethylation and KRAS Mutation Are Independent Predictors of Cetuximab
      Plus FOLFIRI Chemotherapy in Patients with Metastatic Colorectal Cancer.
AB  - PURPOSE: Hypermethylation of the CpG island of p16(INK4a) occurs in a significant
      proportion of colorectal cancer (CRC). We aimed to investigate its predictive
      role in CRC patients treated with 5-fluorouracil, leucovorin, irinotecan
      (FOLFIRI), and cetuximab. MATERIALS AND METHODS: Pyrosequencing was used to
      identify KRAS mutation and hypermethylation of 6 CpG island loci (p16, p14,
      MINT1, MINT2, MINT31, and hMLH1) in DNA extracted from formalin-fixed paraffin
      embedded specimens. Logistic regression and Cox regression were performed for
      analysis of the relation between methylation status of CpG island methylator
      phenotype (CIMP) markers including p16 and clinical outcome. RESULTS:
      Hypermethylation of the p16 gene was detected in 14 of 49 patients (28.6%) and
      showed significant association with KRAS mutation (Fisher exact, p=0.01) and CIMP
      positivity (Fisher exact, p=0.002). Patients with p16-unmethylated tumors had
      significantly longer time to progression (TTP; median, 9.0 months vs. 3.5 months;
      log-rank, p=0.001) and overall survival (median, 44.9 months vs. 16.4 months; log
      rank, p=0.008) than those with p16-methylated tumors. Patients with both KRAS and
      p16 aberrancy (n=6) had markedly shortened TTP (median, 2.8 months) compared to
      those with either KRAS or p16 aberrancy (n=11; median, 8.6 months; p=0.021) or
      those with neither (n=32; median, 9.0 months; p < 0.0001). In multivariate
      analysis, KRAS mutation and p16 methylation showed independent association with
      shorter TTP (KRAS mutation: hazard ratio [HR], 3.21; p=0.017; p16 methylation:
      HR, 2.97; p=0.027). CONCLUSION: Hypermethylation of p16 was predictive of
      clinical outcome in metastatic CRC patients treated with cetuximab and FOLFIRI,
      irrespective of KRAS mutation.

PMID- 25943322
TI  - A Study of Relationship of Atheroembolic Risk Factors with Postoperative Recovery
      in Renal Function after Partial Nephrectomy in Patients Staged T1-2 Renal Cell
      Carcinoma during Median 4-Year Follow-up.
AB  - PURPOSE: The objective of this study is to evaluate the relationship of
      atheroembolic risk factors with postoperative recovery of renal function after on
      clamp partial nephrectomy (PN) with warm ischemia in patients with staged T1-2
      renal cell carcinoma (RCC). MATERIALS AND METHODS: A total of 234 patients from
      2004 to 2012 were included, and their clinicopathologic and operative parameters,
      including atheroembolic risk factors were reviewed retrospectively. Renal
      function, as determined by estimated glomerular filtration rate (eGFR) and
      measurement of serum creatinine level (Cr) at each scheduled follow-up for a
      median four years, was compared between the high-risk (HR) group (n=49, >= five
      risk factors) and the low-risk (LR) group (n=185, < five risk factors). RESULTS:
      Except for baseline renal function and number of risk factors for atheroembolism,
      differences in characteristics between groups were comparatively insignificant.
      At 3 months after the operation, Cr and eGFR differed significantly between the
      two groups (p < 0.05), but no differences were observed afterward. Significant
      deterioration from baseline in Cr and eGFR was observed in both groups at 1 month
      after the operation, with a greater change in the HR group (p < 0.05). From
      measurement to measurement, significantly faster deterioration in Cr and eGFR was
      observed in the HR group than in the LR group until 6 months after the operation
      (Cr: LR, 0.02 mg/dL and HR, 0.13 mg/dL; eGFR: LR, 1.50 mL/min/1.73 m(2) and HR,
      6.38 mL/min/1.73 m(2); p < 0.05). CONCLUSION: The presence of atheroembolic risk
      factors may negatively influence postoperative recovery of renal function after
      PN in patients with localized RCC.

PMID- 25943323
TI  - Novel Methods of Lymph Node Evaluation for Predicting the Prognosis of Colorectal
      Cancer Patients with Inadequate Lymph Node Harvest.
AB  - PURPOSE: Lymph node metastasis is an important factor for predicting the
      prognosis of colorectal cancer patients. However, approximately 60% of patients
      do not receive adequate lymph node evaluation (less than 12 lymph nodes). In this
      study, we identified a more effective tool for predicting the prognosis of
      patients who received inadequate lymph node evaluation. MATERIALS AND METHODS:
      The number of metastatic lymph nodes, total number of lymph nodes examined,
      number of negative metastatic lymph nodes (NL), lymph node ratio (LR), and the
      number of apical lymph nodes (APL) were examined, and the prognostic impact of
      these parameters was examined in patients with colorectal cancer who underwent
      surgery from January 2004 to December 2011. In total, 806 people were analyzed
      retrospectively. RESULTS: In comparison of different lymph node analysis methods
      for rectal cancer patients who did not receive adequate lymph node dissection,
      the LR showed a significant difference in overall survival (OS) and the APL
      predicted a significant difference in disease-free survival (DFS). In the case of
      colon cancer patients who did not receive adequate lymph node dissection, LR
      predicted a significant difference in DFS and OS, and the APL predicted a
      significant difference in DFS. CONCLUSION: If patients did not receive adequate
      lymph node evaluation, the LR and NL were useful parameters to complement N stage
      for predicting OS in colon cancer, whereas LR was complementary for rectal
      cancer. The APL could be used for prediction of DFS in all patients.

PMID- 25943324
TI  - Trends in Cancer Screening Rates among Korean Men and Women: Results of the
      Korean National Cancer Screening Survey, 2004-2013.
AB  - PURPOSE: The Korean National Cancer Screening Survey (KNCSS), a nationwide cross
      sectional survey, has been conducted annually since 2004. The current study was
      conducted to report on the trends in screening rates among Korean men and women,
      and to evaluate policies regarding cancer screening programs implemented to
      reduce the burden of cancer. MATERIALS AND METHODS: The current study used KNCSS
      data. The eligible study population included men aged 40-74 years and women aged
      30-74 years with no cancer history. The lifetime screening rate, screening rate
      with recommendation, and changes in annual rates were calculated for five major
      cancers (i.e., stomach, liver, colorectal, breast, and cervix uteri). RESULTS:
      The screening rates with recommendation increased by 4.2% (95% confidence
      interval [CI], 3.7% to 4.8%) annually for stomach cancer, 1.2% (95% CI, 0.1% to
      2.4%) for liver cancer, 3.0% (95% CI, 1.8% to 4.1%) for colorectal cancer, 3.7%
      (95% CI, 2.7% to 4.8%) for breast cancer, and 1.3% (95% CI, 0.8% to 1.8%) for
      cervical cancer. In 2013, the screening rates with recommendation for stomach,
      liver, colorectal, breast, and cervical cancers were 73.6%, 33.6%, 55.6%, 59.7%,
      and 67.0%, respectively. CONCLUSION: Both the lifetime screening rates and
      screening rates with recommendation for the five above-mentioned cancers
      increased annually from 2004 to 2013.

PMID- 25943325
TI  - Cutaneous metastasis of transitional cell carcinoma of the urinary bladder eight
      years after the primary: a case report.
AB  - INTRODUCTION: Cutaneous metastasis of bladder carcinoma is extremely rare with a
      limited number of published cases. An awareness of this rare clinical entity and
      high index of suspicion is needed for diagnosis, as it can occur months or rarely
      as in this case, even years, after the primary cancer. CASE PRESENTATION: An 81
      year-old Caucasian man presented with a one-year history of increasing left leg
      swelling and a two-month history of a macular-nodular rash on the anterior thigh,
      on a background of a high-grade (WHO Grade 2 of 3) papillary and invasive
      transitional cell carcinoma of the bladder in 2006. Following investigations, he
      was diagnosed as having probable locoregional recurrence of previously resected
      urothelial cancer of the bladder with extensive retrograde lymphatic permeation
      into the left thigh with cutaneous eruptions of malignancy. He completed a
      planned course of palliative radiation therapy to the left thigh lesions (30 Gy
      divided over 10 fractions) as well as the left pelvic node (a total dose of 18 Gy
      divided over six fractions). The disease ran an aggressive course and our patient
      died six months after the diagnosis of cutaneous metastases. CONCLUSIONS:
      Metastatic disease should always be considered in the differential diagnosis in
      patients with a previous history of bladder cancer who present with cutaneous
      nodules, even many years after the initial diagnosis at the primary site.

PMID- 25943326
TI  - Further evidence for the role of gap junctions in the delayed antiarrhythmic
      effect of cardiac pacing.
AB  - The objective of this study was to provide evidence that gap junctions are
      involved in the delayed antiarrhythmic effect of cardiac pacing. Twenty-four dogs
      were paced through the right ventricle (4 * 5 min, rate of 240 beats/min) 24 h
      prior to a 25 min occlusion of the left anterior descending coronary artery. Some
      of these paced dogs were infused with 50 (n = 7) or 100 MUmol/L (n = 7) of the
      gap junction uncoupler carbenoxolone (CBX), prior to and during the occlusion.
      Ten sham-paced dogs, subjected only to occlusion, served as the controls. Cardiac
      pacing markedly reduced the number of ectopic beats and episodes of ventricular
      tachycardia (VT), as well the incidence of VT and ventricular fibrillation during
      occlusion. The changes in severity of ischaemia and tissue electrical resistance
      were also less marked compared with the unpaced controls. Pacing also preserved
      the permeability of gap junctions, the phosphorylation of connexin43, and the
      structural integrity of the intercalated discs. The closing of gap junctions with
      CBX prior to and during ischaemia markedly attenuated or even abolished these
      protective effects of pacing. CONCLUSION: Our results support the previous
      findings that gap junctions play a role in the delayed antiarrhythmic effect of
      cardiac pacing.

PMID- 25943327
TI  - A novel splice site mutation in SMARCAL1 results in aberrant exon definition in a
      child with Schimke immunoosseous dysplasia.
AB  - Schimke Immunoosseous Dysplasia (SIOD) is a rare, autosomal recessive disorder of
      childhood characterized by spondyloepiphyseal dysplasia, focal segmental
      glomerulosclerosis and renal failure, T-cell immunodeficiency, and cancer in
      certain instances. Approximately half of patients with SIOD are reported to have
      biallelic mutations in SMARCAL1 (SWI/SNF-related matrix-associated actin
      dependent regulator of chromatin, subfamily a-like 1), which encodes a DNA
      translocase that localizes to sites of DNA replication and repairs damaged
      replication forks. We present a novel mutation (NM_014140.3:c.2070+2insT) that
      results in defective SMARCAL1 mRNA splicing in a child with SIOD. This mutation,
      within the donor site of intron 12, results in the skipping of exon 12, which
      encodes part of a critical hinge region connecting the two lobes of the ATPase
      domain. This mutation was not recognized as deleterious by diagnostic SMARCAL1
      sequencing, but discovered through next generation sequencing and found to result
      in absent SMARCAL1 expression in patient-derived lymphoblasts. The splicing
      defect caused by this mutation supports the concept of exon definition.
      Furthermore, it illustrates the need to broaden the search for SMARCAL1 mutations
      in patients with SIOD lacking coding sequence variants.

PMID- 25943329
TI  - Salinity changes impact of hazardous chemicals in Enchytraeus albidus.
AB  - Supralittoral ecosystems are among the most challenging environments for soil
      organisms, particularly when salinity fluctuations are involved, frequently
      combined with the presence of contaminants as a result of intense anthropogenic
      activities. Knowledge of how salinity influences the effect of contaminants in
      supralittoral species is crucial for determining the safety factors required when
      extrapolating results from optimal laboratory conditions to these natural
      ecosystems. The present study therefore evaluated the effects of 2 metals (copper
      and cadmium) and 2 organic compounds (carbendazim and 4-nonylphenol) in the
      absence or presence of 150/00 NaCl in the potworm Enchytraeus albidus, a model
      organism for ecotoxicology studies commonly found in supralittoral ecosystems,
      The potworms had a higher reproduction in saline soil than in control soil.
      Moreover, the effects of copper and carbendazim on reproduction were smaller than
      when they were tested in nonsaline soil. Potworms exposed to nonsaline soils also
      had significantly higher tissue concentrations of metals, which partly explains
      the effects on reproduction. The influence of salinity on effects of 4
      nonylphenol was, however, less clear; effects on survival decreased in saline
      soil, but effects on reproduction were highest in saline soil. The latter
      slightly correlated with tissue concentrations of the chemical. The present study
      provides the first evidence that soil salinity has a significant influence on the
      impact of contaminants evaluated with the enchytraeid reproduction test.

PMID- 25943330
TI  - Fishing upstream: health and the social history.

PMID- 25943328
TI  - A simple approach to evaluate the kinetic rate constant for ATP synthesis in
      resting human skeletal muscle at 7 T.
AB  - Inversion transfer (IT) is a well-established technique with multiple attractive
      features for analysis of kinetics. However, its application in measurement of ATP
      synthesis rate in vivo has lagged behind the more common saturation transfer (ST)
      techniques. One well-recognized issue with IT is the complexity of data analysis
      in comparison with much simpler analysis by ST. This complexity arises, in part,
      because the gamma-ATP spin is involved in multiple chemical reactions and
      magnetization exchanges, whereas Pi is involved in a single reaction, Pi -> gamma
      ATP. By considering the reactions involving gamma-ATP only as a lumped constant,
      the rate constant for the reaction of physiological interest, kPi->gammaATP , can
      be determined. Here, we present a new IT data analysis method to evaluate kPi
      >gammaATP using data collected from resting human skeletal muscle at 7 T. The
      method is based on the basic Bloch-McConnell equation, which relates kPi
      >gammaATP to mPi, the rate of Pi magnetization change. The kPi->gammaATP value is
      accessed from mPi data by more familiar linear correlation approaches. For a
      group of human subjects (n = 15), the kPi->gammaATP value derived for resting
      calf muscle was 0.066 +/- 0.017 s(-1) , in agreement with literature-reported
      values. In this study we also explored possible time-saving strategies to speed
      up data acquisition for kPi->gammaATP evaluation using simulations. The analysis
      indicates that it is feasible to carry out a (31) P IT experiment in about 10 min
      or less at 7 T with reasonable outcome in kPi->gammaATP variance for measurement
      of ATP synthesis in resting human skeletal muscle. We believe that this new IT
      data analysis approach will facilitate the wide acceptance of IT to evaluate ATP
      synthesis rate in vivo. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 25943331
TI  - The current state of e-prescribing: Implications for advanced practice registered
      nurses.
AB  - PURPOSE: The purpose of this study was to review legislation, barriers and
      challenges, and current state of e-prescribing (eRx) in the United States. DATA
      SOURCES: Literature search of CINAHL, MEDLINE, PubMed, and Google Scholar was
      performed. CONCLUSIONS: Challenges to eRx implementation and effective use
      include transcription, workflow issues, alert fatigue, educational and tangible
      reminders, and eRx of controlled substances. IMPLICATIONS FOR PRACTICE: Further
      research could be best focused on user-friendly and interactive software
      improvements for both patient and provider use, bidirectional communication, and
      workflow studies to improve efficiency of eRx.

PMID- 25943332
TI  - Controlling the Formation of Ionic-Liquid-based Aqueous Biphasic Systems by
      Changing the Hydrogen-Bonding Ability of Polyethylene Glycol End Groups.
AB  - The formation of aqueous biphasic systems (ABS) when mixing aqueous solutions of
      polyethylene glycol (PEG) and an ionic liquid (IL) can be controlled by modifying
      the hydrogen-bond-donating/-accepting ability of the polymer end groups. It is
      shown that the miscibility/immiscibility in these systems stems from both the
      solvation of the ether groups in the oxygen chain and the ability of the PEG
      terminal groups to preferably hydrogen bond with water or the anion of the salt.
      The removal of even one hydrogen bond in PEG can noticeably affect the phase
      behavior, especially in the region of the phase diagram in which all the ethylene
      oxide (EO) units of the polymeric chain are completely solvated. In this region,
      removing or weakening the hydrogen-bond-donating ability of PEG results in
      greater immiscibility, and thus, in a higher ability to form ABS, as a result of
      the much weaker interactions between the IL anion and the PEG end groups. 

PMID- 25943333
TI  - Prospective study of a molecular selection profile for RAS wild type colorectal
      cancer patients receiving irinotecan-cetuximab.
AB  - BACKGROUND: The aim of our study was to evaluate whether a panel of biomarkers,
      prospectively analysed might be able to predict patients' clinical outcome more
      accurately than RAS status alone. METHODS: K-RAS (exons 2, 3, 4) wild type
      colorectal cancer patients, candidates to second/third-line cetuximab with
      chemotherapy were prospectively allocated into 2 groups on the basis of their
      profile: favourable (BRAF and PIK3CA exon 20 wild type, EGFR GCN >= 2.6, HER-3
      Rajkumar score <= 8, IGF-1 immunostaining < 2) or unfavourable (any of the
      previous markers altered or mutated). After the introduction of N-RAS status
      (exons 2, 3, 4) only RAS wild type patients were considered eligible. Primary aim
      was response rate (RR). To detect a difference in terms of RR among patients with
      an unfavourable profile (estimated around 25%) and patients with a favourable
      profile (estimated around 60%), with a probability alpha of 0.05 and beta of
      0.05, required sample size was 46 patients. Secondary endpoints were progression
      free survival (PFS) and overall survival (OS). RESULTS: Forty-six patients were
      enrolled. Seventeen patients (37%) were allocated to the favourable and 29
      patients (63%) to the unfavourable profile. RR in the favourable and unfavourable
      group was 11/17 (65%) and 2/29 (7%) (p = 0.007) respectively. The favourable
      group also showed an improved PFS (8 months vs. 3 months, p < 0.0001) and OS (15
      months vs. 6 months, p < 0.0001). CONCLUSIONS: Our results suggest that
      prospective selection of optimal candidates for cetuximab treatment is feasible
      and may be able to improve clinical outcome.

PMID- 25943335
TI  - Autonomous Motivation Predicts 7-Day Physical Activity in Hong Kong Students.
AB  - Autonomous motivation predicts positive health behaviors such as physical
      activity. However, few studies have examined the relation between motivational
      regulations and objectively measured physical activity and sedentary behaviors.
      Thus, we investigated whether different motivational regulations (autonomous
      motivation, controlled motivation, and amotivation) predicted 7-day physical
      activity, sedentary behaviors, and health-related quality of life (HRQoL) of
      students. A total of 115 students (mean age = 11.6 years, 55.7% female) self
      reported their motivational regulations and health-related quality of life.
      Physical activity and sedentary behaviors were measured using accelerometers for
      seven days. Using multilevel modeling, we found that autonomous motivation
      predicted higher levels of moderate-to-vigorous physical activity, less sedentary
      behaviors, and better HRQoL. Controlled motivation and amotivation each only
      negatively predicted one facet of HRQoL. Results suggested that autonomous
      motivation could be an important predictor of physical activity behaviors in Hong
      Kong students. Promotion of this form of motivational regulation may also
      increase HRQoL.

PMID- 25943334
TI  - Risk Assessment of the Carbon Nanotube Group.
AB  - This study assessed the health risks via inhalation and derived the occupational
      exposure limit (OEL) for the carbon nanotube (CNT) group rather than individual
      CNT material. We devised two methods: the integration of the intratracheal
      instillation (IT) data with the inhalation (IH) data, and the "biaxial approach."
      A four-week IH test and IT test were performed in rats exposed to representative
      materials to obtain the no observed adverse effect level, based on which the OEL
      was derived. We used the biaxial approach to conduct a relative toxicity
      assessment of six types of CNTs. An OEL of 0.03 mg/m(3) was selected as the
      criterion for the CNT group. We proposed that the OEL be limited to 15 years. We
      adopted adaptive management, in which the values are reviewed whenever new data
      are obtained. The toxicity level was found to be correlated with the Brunauer
      Emmett-Teller (BET)-specific surface area (BET-SSA) of CNT, suggesting the BET
      SSA to have potential for use in toxicity estimation. We used the published
      exposure data and measurement results of dustiness tests to compute the risk in
      relation to particle size at the workplace and showed that controlling micron
      sized respirable particles was of utmost importance. Our genotoxicity studies
      indicated that CNT did not directly interact with genetic materials. They
      supported the concept that, even if CNT is genotoxic, it is secondary
      genotoxicity mediated via a pathway of genotoxic damage resulting from oxidative
      DNA attack by free radicals generated during CNT-elicited inflammation. Secondary
      genotoxicity appears to involve a threshold. 

PMID- 25943336
TI  - How can nurses support relatives of a dying patient with the organ donation
      option?
AB  - BACKGROUND: The UK Department of Health in 2008 established the Organ Donation
      Taskforce to improve organ donation within the UK. Knowing how nurses can best
      support families during this time is important to maintain best practice. AIMS:
      The purpose of the literature review was to summarise evidence related to nursing
      support for a dying patient's family with the option of organ donation. SEARCH
      STRATEGY: The (a) Allied Medical Education Database (AMED), (b) British Nursing
      Index (BNI), (c) Cochrane Library, (d) Cumulative Index to Nursing and Allied
      Health Literature (CINAHL), (e) NHS Evidence, and (f) PubMed were searched during
      January to May 2013 using the key words: organ donation, nurse, support, organ
      donor, family. A total of 23 articles were critiqued to synthesise available
      evidence over 25 years. INCLUSION AND EXCLUSION CRITERIA: Primary sources
      addressing deceased organ donors, their families and nurses, written in English,
      in peer reviewed journals over the last 25 years and conducted internationally
      were included. Articles related to consent, attitudes towards donation and
      physicians' views were excluded. FINDINGS: Two major themes emerged: (a) clarity
      of communication and understanding of information and (b) the nurse's competency.
      CONCLUSIONS: This study adds to the topic by addressing support needed by a
      family. Correct information given to a family clearly, sensitively and in a
      professional manner can accommodate relatives' understanding why their loved one
      is in a critical condition, which can help them accept death and therefore
      consider the option of organ donation. Nurses must acquire through regular
      training specific skills and knowledge in order to practice efficiently and
      adhere to the needs of a dying patient's family. RELEVANCE TO CLINICAL PRACTICE:
      By incorporating organ donation as a norm in end-of-life care, bereavement needs
      can be addressed in addition to improving organ donation rates.

PMID- 25943337
TI  - Rapid and marker-free refactoring of xylose-fermenting yeast strains with
      Cas9/CRISPR.
AB  - Genomic integration of expression cassettes containing heterologous genes into
      yeast with traditional methods inevitably deposits undesirable genetic elements
      into yeast chromosomes, such as plasmid-borne multiple cloning sites, antibiotic
      resistance genes, Escherichia coli origins, and yeast auxotrophic markers.
      Specifically, drug resistance genes for selecting transformants could hamper
      further industrial usage of the resulting strains because of public health
      concerns. While we constructed an efficient and rapid xylose-fermenting
      Saccharomyces cerevisiae, the engineered strain (SR8) might not be readily used
      for a large-scale fermentation because the SR8 strain contained multiple copies
      of drug resistance genes. We utilized the Cas9/CRISPR-based technique to refactor
      an efficient xylose-fermenting yeast strain without depositing any undesirable
      genetic elements in resulting strains. In order to integrate genes (XYL1, XYL2,
      and XYL3) coding for xylose reductase, xylitol dehydrogenase, and xylulokinase
      from Scheffersomyces stipitis, and delete both PHO13 and ALD6, a double-strand
      break formation by Cas9 and its repair by homologous recombination were
      exploited. Specifically, plasmids containing guide RNAs targeting PHO13 and ALD6
      were sequentially co-transformed with linearized DNA fragments containing XYL1,
      XYL2, and XYL3 into S. cerevisiae expressing Cas9. As a result, two copies of
      XYL1, XYL2, and XYL3 were integrated into the loci of PHO13 and ALD6 for
      achieving overexpression of heterologous genes and knockout of endogenous genes
      simultaneously. With further prototrophic complementation, we were able to
      construct an engineered strain exhibiting comparable xylose fermentation
      capabilities with SR8 within 3 weeks. We report a detailed procedure for
      refactoring xylose-fermenting yeast using any host strains. The refactored
      strains using our procedure could be readily used for large-scale fermentations
      since they have no antibiotic resistant markers.

PMID- 25943339
TI  - Highly active chromium(III) complexes based on tridentate pyrazolyl pyridyl
      ligands for ethylene polymerization and oligomerization.
AB  - A set of new chromium(III) [Cr(III)] complexes based on the tridentate ligand
      HC(Pz)2Py (Pz = pyrazole; Py = pyridine) and its derivatives were prepared,
      characterized, and evaluated for ethylene polymerization/oligomerization. X-ray
      single-crystal analyses of the Cr(III) complexes showed tridentate coordination
      on the fac-octahedral Cr sphere. Upon activation with methylaluminoxane (MAO),
      the precatalysts and the ligands L1-L3 mixed in situ with Cr(acac)3 were highly
      active and generally produced polyethylene as a major product. Their catalytic
      performances were markedly affected by the substituents on the methine carbon
      atom of the ligands and reaction conditions.

PMID- 25943338
TI  - Nucleic acid reactivity: challenges for next-generation semiempirical quantum
      models.
AB  - Semiempirical quantum models are routinely used to study mechanisms of RNA
      catalysis and phosphoryl transfer reactions using combined quantum mechanical
      (QM)/molecular mechanical methods. Herein, we provide a broad assessment of the
      performance of existing semiempirical quantum models to describe nucleic acid
      structure and reactivity to quantify their limitations and guide the development
      of next-generation quantum models with improved accuracy. Neglect of diatomic
      differential overlap and self-consistent density-functional tight-binding
      semiempirical models are evaluated against high-level QM benchmark calculations
      for seven biologically important datasets. The datasets include: proton
      affinities, polarizabilities, nucleobase dimer interactions, dimethyl phosphate
      anion, nucleoside sugar and glycosidic torsion conformations, and RNA phosphoryl
      transfer model reactions. As an additional baseline, comparisons are made with
      several commonly used density-functional models, including M062X and B3LYP (in
      some cases with dispersion corrections). The results show that, among the
      semiempirical models examined, the AM1/d-PhoT model is the most robust at
      predicting proton affinities. AM1/d-PhoT and DFTB3-3ob/OPhyd reproduce the MP2
      potential energy surfaces of 6 associative RNA phosphoryl transfer model
      reactions reasonably well. Further, a recently developed linear-scaling "modified
      divide-and-conquer" model exhibits the most accurate results for binding energies
      of both hydrogen bonded and stacked nucleobase dimers. The semiempirical models
      considered here are shown to underestimate the isotropic polarizabilities of
      neutral molecules by approximately 30%. The semiempirical models also fail to
      adequately describe torsion profiles for the dimethyl phosphate anion, the
      nucleoside sugar ring puckers, and the rotations about the nucleoside glycosidic
      bond. The modeling of pentavalent phosphorus, particularly with thio
      substitutions often used experimentally as mechanistic probes, was problematic
      for all of the models considered. Analysis of the strengths and weakness of the
      models suggests that the creation of robust next-generation models should
      emphasize the improvement of relative conformational energies and barriers, and
      nonbonded interactions.

PMID- 25943340
TI  - Evolution of proteasome regulators in eukaryotes.
AB  - All living organisms require protein degradation to terminate biological
      processes and remove damaged proteins. One such machine is the 20S proteasome, a
      specialized barrel-shaped and compartmentalized multicatalytic protease. The
      activity of the 20S proteasome generally requires the binding of
      regulators/proteasome activators (PAs), which control the entrance of substrates.
      These include the PA700 (19S complex), which assembles with the 20S and forms the
      26S proteasome and allows the efficient degradation of proteins usually labeled
      by ubiquitin tags, PA200 and PA28, which are involved in proteolysis through
      ubiquitin-independent mechanisms and PI31, which was initially identified as a
      20S inhibitor in vitro. Unlike 20S proteasome, shown to be present in all
      Eukaryotes and Archaea, the evolutionary history of PAs remained fragmentary.
      Here, we made a comprehensive survey and phylogenetic analyses of the four types
      of regulators in 17 clades covering most of the eukaryotic supergroups. We found
      remarkable conservation of each PA700 subunit in all eukaryotes, indicating that
      the current complex PA700 structure was already set up in the last eukaryotic
      common ancestor (LECA). Also present in LECA, PA200, PA28, and PI31 showed a more
      contrasted evolutionary picture, because many lineages have subsequently lost one
      or two of them. The paramount conservation of PA700 composition in all eukaryotes
      and the dynamic evolution of PA200, PA28, and PI31 are discussed in the light of
      current knowledge on their physiological roles. 

PMID- 25943342
TI  - Associations between subjective social status and physical and mental health
      functioning among patients with hypertension.
AB  - We examine the cross-sectional association between subjective social status and
      self-rated physical and mental health functioning in 518 Black and White patients
      enrolled in a community-based hypertension control research study. We found that
      (1) subjective social status, measured using both a proximal and distal referent
      group, was positively associated with physical and mental health functioning
      scores independent of educational level, household income, or both; (2) the
      effect of subjective social status on physical and mental health functioning
      differed significantly by race when using the distal, not the proximal, referent
      group. When the associations differed, they were stronger for Whites than Blacks.

PMID- 25943341
TI  - Differential Expression of Genes that Control Respiration Contribute to Thermal
      Adaptation in Redband Trout (Oncorhynchus mykiss gairdneri).
AB  - Organisms can adapt to local environmental conditions as a plastic response or
      become adapted through natural selection on genetic variation. The ability to
      adapt to increased water temperatures will be of paramount importance for many
      fish species as the climate continues to warm and water resources become limited.
      Because increased water temperatures will reduce the dissolved oxygen available
      for fish, we hypothesized that adaptation to low oxygen environments would
      involve improved respiration through oxidative phosphorylation (OXPHOS). To test
      this hypothesis, we subjected individuals from two ecologically divergent
      populations of inland (redband) rainbow trout (Oncorhynchus mykiss gairdneri)
      with historically different temperature regimes (desert and montane) and their F1
      progeny to diel cycles of temperature stress and then examined gene expression
      data for 80 nuclear- and mitochondrial-encoded OXPHOS subunits that participate
      in respiration. Of the 80 transcripts, 7 showed >= 2-fold difference in
      expression levels in gill tissue from desert fish under heat stress whereas the
      montane fish had none and the F1 only had one differentially expressed gene. A
      structural analysis of the proteins encoded by those genes suggests that the
      response could coordinate the formation of supercomplexes and oligomers.
      Supercomplexes may increase the efficiency of respiration because complexes I,
      III, and IV are brought into close proximity and oligomerization of complex V
      alters the macrostructure of mitochondria to improve respiration. Significant
      differences in gene expression patterns in response to heat stress in a common
      environment indicate that the response was not due to plasticity but had a
      genetic basis. 

PMID- 25943343
TI  - Patient experiences of awake craniotomy: An Interpretative Phenomenological
      Analysis.
AB  - Awake craniotomy with language mapping enables maximum resection of tumours in
      eloquent areas while preserving function. This study aims to understand the lived
      experiences of those undergoing an awake craniotomy. Six participants who
      underwent awake craniotomy were interviewed, and the data were analysed using
      Interpretative Phenomenological Analysis. Themes were identified as 'Unspeakable
      Fear', 'Dissociation' and 'Control and Responsibility'. Participants discussed
      how surgery was a threat to the sense of self. Dissociation during surgery
      operated as a protective mechanism, while the surgical team all had roles in
      maintaining this bubble of dissociation, such as being a support to the patient's
      emotional needs.

PMID- 25943344
TI  - Tuning noise in gene expression.
AB  - The relative contribution of promoter architecture and the associated chromatin
      environment in regulating gene expression noise has remained elusive. In their
      recent work, Arkin, Schaffer and colleagues (Dey et al, 2015) show that mean
      expression and noise for a given promoter at different genomic loci are
      uncorrelated and influenced by the local chromatin environment.

PMID- 25943346
TI  - Imaging characteristics and safety of florbetapir (18F) in Japanese healthy
      volunteers, patients with mild cognitive impairment and patients with Alzheimer's
      disease.
AB  - OBJECTIVE: The purpose of this study was to evaluate the performance
      characteristics and safety of florbetapir ((I8)F) positron emission tomography
      (PET) in patients with Alzheimer's disease (AD) and mild cognitive impairment
      (MCI) and cognitively normal (CN) control patients from Japan. METHODS:
      Florbetapir ((I8)F) PET was obtained in 48 subjects (15 AD patients, 15 MCI
      patients, and 18 CNs) within a multicenter phase 2/3 study. Amyloid burden was
      assessed visually and classified as positive or negative for pathologic levels of
      amyloid aggregation, blind to diagnostic classification. Cerebral to cerebellar
      standardized uptake value ratios (SUVRs) were determined from the florbetapir
      ((I8)F) PET images. Safety was assessed by monitoring adverse events, vital
      signs, clinical laboratory assessments, and electrocardiograms. Demographic
      variables and cognitive scales were summarized by using descriptive statistics
      for each group. Fisher's exact test and one-way analysis of variance were used to
      compare amyloid positivity and mean SUVRs, respectively, between diagnostic
      groups. RESULTS: Florbetapir ((I8)F) PET was rated visually amyloid positive in
      80.0% of AD patients, 33.3% of MCI patients, and 16.7% of CNs. Mean SUVRs were
      highest in the AD group and lowest in the CN group for each brain region (P <
      0.01) and globally (P < 0.05). Kappa statistics showed strong inter-reader
      agreement (Fleiss' kappa = 0.82) and individual reader's agreement with the
      majority of readers (kappa ranged from 0.79 to 1.0). Seventeen of the 48 subjects
      (35.4%) were Apolipoprotein E genotype epsilon4 positive, which included 10
      subjects in the AD group and 7 subjects in the MCI group. A total of 6 subjects
      (5 of whom were in the CN group) had at least 1 treatment-emergent adverse event
      (TEAE). CONCLUSIONS: These data indicate that amyloid positivity increased with
      diagnostic category (CN < MCI < AD) and are consistent with expected rates of
      amyloid positivity among individuals with clinical diagnoses of AD and MCI. In
      addition, these results were similar to those obtained in United States studies.
      Florbetapir ((18)F) was safe and well tolerated. The reliability of both
      qualitative and quantitative assessments of florbetapir ((18)F) in this study
      population provides support for potential use in clinical settings in Japan.

PMID- 25943345
TI  - Orthogonal control of expression mean and variance by epigenetic features at
      different genomic loci.
AB  - While gene expression noise has been shown to drive dramatic phenotypic
      variations, the molecular basis for this variability in mammalian systems is not
      well understood. Gene expression has been shown to be regulated by promoter
      architecture and the associated chromatin environment. However, the exact
      contribution of these two factors in regulating expression noise has not been
      explored. Using a dual-reporter lentiviral model system, we deconvolved the
      influence of the promoter sequence to systematically study the contribution of
      the chromatin environment at different genomic locations in regulating expression
      noise. By integrating a large-scale analysis to quantify mRNA levels by smFISH
      and protein levels by flow cytometry in single cells, we found that mean
      expression and noise are uncorrelated across genomic locations. Furthermore, we
      showed that this independence could be explained by the orthogonal control of
      mean expression by the transcript burst size and noise by the burst frequency.
      Finally, we showed that genomic locations displaying higher expression noise are
      associated with more repressed chromatin, thereby indicating the contribution of
      the chromatin environment in regulating expression noise. 

PMID- 25943347
TI  - Image accuracy and quality test in rate constant depending on reconstruction
      algorithms with and without incorporating PSF and TOF in PET imaging.
AB  - OBJECTIVE: Positron emission tomography allows imaging of patho-physiological
      information as a form of rate constants from scanned and reconstructed dynamic
      image. Some reconstruction algorithms incorporated with time of flight and point
      spread function have been developed, and quantitative accuracy and quality in the
      image have been investigated. However, feasibility of the rate constants from the
      dynamic image has not been directly investigated. We investigated the accuracy
      and quality in the rate constant by scanning a phantom filled simultaneously with
      (11)C and (18)F. METHOD: We utilized a phantom filled with (18)F-F(-) solution in
      the main cylinder and with (11)C-flumazenil solution in seven sub-cylinders. The
      phantom was scanned by a Biograph mCT and the scanned data were reconstructed
      with FBP- and OSEM-based algorithms incorporating with and without TOF and/or PSF
      corrections. Decay rate images as kinetic rate constant were computed for all the
      reconstructed images and quantitative accuracy and quality in the rate images
      were investigated. RESULTS: The obtained decay rates were not significantly
      different from the reference values for both isotopes for all applied algorithms
      when noise on image was not large. Respective SD was smaller in OSEM with TOF in
      the (11)C-filled region. CONCLUSION: The present study suggests that OSEM
      incorporating with TOF provides reasonable quantitative accuracy and image
      quality regarding decay rates.

PMID- 25943348
TI  - Complement activation, placental malaria infection, and birth weight in areas
      characterized by unstable malaria transmission in central Sudan.
AB  - BACKGROUND: The pathogenesis of malaria during pregnancy is not completely
      understood. There are few published data on complement activation and malaria
      during pregnancy. This study aimed to investigate complement activation and
      malaria during pregnancy, and their association with hemoglobin and birth weight.
      METHODS: A cross-sectional study was conducted at Medani, Sudan. Soluble terminal
      complement complex (TCC) levels were measured using ELISA in maternal and cord
      blood samples from 126 parturient women. RESULTS: There were no Plasmodium
      falciparum-positive blood films from maternal peripheral blood, the placenta, or
      cord blood samples. Three (2.4%) and 22 (17.5%) of the placentas showed chronic
      and previous infection with histopathological examination, respectively, while
      101 (80.2%) of them had no malaria infection. The mean [SD] of the maternal (22.4
      [6.1] vs. 26.5 [3.5] ng/ml, P < 0.001) and cord blood (24.5 [4.5] vs. 26.8 [4.4]
      ng/ml, P = 0.024) TCC levels were significantly lower in cases of placental
      malaria infection (n = 25) than in those without placental malaria infection (n =
      101). Linear regression showed that placental malaria infection was significantly
      associated with birth weight (-0.353 g, P = 0.013), but there were no
      associations between maternal and cord TCC levels and maternal hemoglobin, or
      between TCC levels and birth weight. CONCLUSION: Maternal and cord blood TCC
      levels are lower in women with placental malaria infection than in those without
      placental malaria infection. VIRTUAL SLIDE: The virtual slide(s) for this article
      can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/9600054761463915.

PMID- 25943349
TI  - The association of body size in early to mid-life with adult urinary 6
      sulfatoxymelatonin levels among night shift health care workers.
AB  - BACKGROUND: Adult body mass index (BMI) has been associated with urinary
      melatonin levels in humans; however, whether earlier-life body size is associated
      with melatonin, particularly among night shift workers, remains unknown. METHODS:
      We evaluated associations of birth weight, body shape (or somatotype) at ages 5
      and 10, BMI at age 18 and adulthood, weight change since age 18, waist
      circumference, waist to hip ratio, and height with creatinine-adjusted morning
      urinary melatonin (6-sulfatoxymelatonin, aMT6s) levels among 1,343 healthy women
      (aged 32-53 at urine collection, 1996-1999) in the Nurses' Health Study (NHS) II
      cohort. Using multivariable linear regression, we computed least-square mean
      aMT6s levels across categories of body size, and evaluated whether these
      associations were modified by night shift work. RESULTS: Adult BMI was inversely
      associated with aMT6s levels (mean aMT6s levels = 34 vs. 50 ng/mg creatinine,
      comparing adult BMI >= 30 vs. <20 kg/m(2); P trend < 0.0001); however, other
      measures of body size were not related to aMT6s levels after accounting for adult
      BMI. Night shifts worked prior to urine collection, whether recent or
      cumulatively over time, did not modify the association between adult BMI and
      aMT6s levels (e.g., P interaction = 0.72 for night shifts worked within two weeks
      of urine collection). CONCLUSIONS: Our results suggest that adult BMI, but not
      earlier measures of body size, is associated with urinary aMT6s levels in
      adulthood. These observations did not vary by night shift work status, and
      suggest that adult BMI may be an important mechanism by which melatonin levels
      are altered and subsequently influence chronic disease risk.

PMID- 25943350
TI  - UNICANCER-PEGASE 07 study: a randomized phase III trial evaluating postoperative
      docetaxel-5FU regimen after neoadjuvant dose-intense chemotherapy for treatment
      of inflammatory breast cancer.
AB  - BACKGROUND: Inflammatory breast cancer (IBC) is a rare and aggressive disease
      requiring a multimodal treatment. We evaluated the benefit of adding docetaxel-5
      fluorouracil (D-5FU) regimen after preoperative dose-intense (DI) epirubicin
      cyclophosphamide (EC) and locoregional treatment in IBC patients. PATIENTS AND
      METHODS: PEGASE 07 was a national randomized phase III open-label study involving
      14 hospitals in France. Women with nonmetastatic IBC were eligible and randomly
      assigned to receive either four cycles of DI EC (E 150 mg/m(2) and C 4000 mg/m(2)
      every 3 weeks with repeated hematopoietic stem cell support), then mastectomy
      with axillary lymph node dissection, and radiotherapy (arm A) or the same
      treatment followed by four cycles of D-5FU (D 85 mg/m(2), day 1 and 5FU 750
      mg/m(2)/day continuous infusion, days 1-5 every 3 weeks) administered
      postradiotherapy (arm B). Patients with hormone receptor-positive tumors received
      hormonal therapy. Disease-free survival (DFS) was the primary end point.
      Secondary end points included tolerance, pathological complete response (pCR)
      rate, and overall survival (OS). RESULTS: Between January 2001 and May 2005, 174
      patients were enrolled and treated (87 in each arm). Median follow-up was similar
      in both arms: 59.6 months [95% confidence interval (CI) 58.4-60.3] in arm A and
      60.5 months (95% CI 58.3-61.4) in arm B. The estimated 5-year DFS rates were not
      different: 55% (95% CI 43.9-64.7) in arm A and 55.5% (95% CI 44.3-65.3) in arm B
      [hazard ratio (HR) = 0.94 (0.61-1.48); P = 0.81]. Identical results were observed
      for 5-year OS: 70.2% (95% CI 59.1-78.8) in arm A and 70% (95% CI 58.8-78.7) in
      arm B [HR = 0.93 (0.55-1.60); P = 0.814]. Following DI EC induction, in-breast
      and global (breast plus nodes) pCR were 28.9% and 20.1%, respectively. Estrogen
      receptor and pCR status were independently associated with survival. CONCLUSION:
      The addition of D-5FU after preoperative DI EC and standard local therapy did not
      improve DFS in IBC. CLINICAL TRIAL NUMBER: ClinicalTrials.gov identifier:
      NCT02324088.

PMID- 25943351
TI  - Actin cytoskeletal remodeling with protrusion formation is essential for heart
      regeneration in Hippo-deficient mice.
AB  - The mammalian heart regenerates poorly, and damage commonly leads to heart
      failure. Hippo signaling is an evolutionarily conserved kinase cascade that
      regulates organ size during development and prevents adult mammalian
      cardiomyocyte regeneration by inhibiting the transcriptional coactivator Yap,
      which also responds to mechanical signaling in cultured cells to promote cell
      proliferation. To identify Yap target genes that are activated during
      cardiomyocyte renewal and regeneration, we performed Yap chromatin
      immunoprecipitation sequencing (ChIP-Seq) and mRNA expression profiling in Hippo
      signaling-deficient mouse hearts. We found that Yap directly regulated genes
      encoding cell cycle progression proteins, as well as genes encoding proteins that
      promote F-actin polymerization and that link the actin cytoskeleton to the
      extracellular matrix. Included in the latter group were components of the
      dystrophin glycoprotein complex, a large molecular complex that, when defective,
      results in muscular dystrophy in humans. Cardiomyocytes near the scar tissue of
      injured Hippo signaling-deficient mouse hearts showed cellular protrusions
      suggestive of cytoskeletal remodeling. The hearts of mdx mutant mice, which lack
      functional dystrophin and are a model for muscular dystrophy, showed impaired
      regeneration and cytoskeleton remodeling, but normal cardiomyocyte proliferation,
      after injury. Our data showed that, in addition to genes encoding cell cycle
      progression proteins, Yap regulated genes that enhance cytoskeletal remodeling.
      Thus, blocking the Hippo pathway input to Yap may tip the balance so that Yap
      responds to mechanical changes associated with heart injury to promote repair. 

PMID- 25943352
TI  - Feedback circuitry between miR-218 repression and RTK activation in glioblastoma.
AB  - Receptor tyrosine kinase (RTK) signaling promotes the growth and progression of
      glioblastoma (GBM), a highly aggressive type of brain tumor. We previously
      reported that decreased miR-218 expression in GBM directly promotes RTK activity
      by increasing the expression of key RTKs and their signaling mediators, including
      the RTK epidermal growth factor receptor (EGFR), phospholipase C-gamma1
      (PLCgamma1), and the kinases PIK3CA and ARAF. However, increased RTK signaling
      usually activates negative feedback mechanisms to maintain homeostasis. We found
      that decreased miR-218 expression in GBM cells also increased the expression of
      genes encoding additional upstream and downstream components of RTK signaling
      pathways, including the RTK platelet-derived growth factor receptor alpha
      (PDGFRalpha) and the kinases ribosomal S6 kinase 2 (RSK2) and S6 kinase 1 (S6K1),
      that collectively overrode the negative feedback mechanism. Furthermore,
      increased RTK signaling itself suppressed miR-218 expression. Mass spectrometry
      and DNA pull-down identified binding of signal transducer and activator of
      transcription 3 (STAT3) along with the transcriptional repressor BCL2-associated
      transcription factor 1 (BCLAF1) directly to the miR-218 locus. These data
      identify previously unknown feedback loops by which miR-218 repression promotes
      increased RTK signaling in high-grade gliomas. 

PMID- 25943353
TI  - Nitrate sensing and uptake in Arabidopsis are enhanced by ABI2, a phosphatase
      inactivated by the stress hormone abscisic acid.
AB  - Living organisms sense and respond to changes in nutrient availability to cope
      with diverse environmental conditions. Nitrate (NO3-) is the main source of
      nitrogen for plants and is a major component in fertilizer. Unraveling the
      molecular basis of nitrate sensing and regulation of nitrate uptake should enable
      the development of strategies to increase the efficiency of nitrogen use and
      maximize nitrate uptake by plants, which would aid in reducing nitrate pollution.
      NPF6.3 (also known as NRT1.1), which functions as a nitrate sensor and
      transporter; the kinase CIPK23; and the calcium sensor CBL9 form a complex that
      is crucial for nitrate sensing in Arabidopsis thaliana. We identified two
      additional components that regulate nitrate transport, sensing, and signaling:
      the calcium sensor CBL1 and protein phosphatase 2C family member ABI2, which is
      inhibited by the stress-response hormone abscisic acid. Bimolecular fluorescence
      complementation assays and in vitro kinase assays revealed that ABI2 interacted
      with and dephosphorylated CIPK23 and CBL1. Coexpression studies in Xenopus
      oocytes and analysis of plants deficient in ABI2 indicated that ABI2 enhanced
      NPF6.3-dependent nitrate transport, nitrate sensing, and nitrate signaling. These
      findings suggest that ABI2 may functionally link stress-regulated control of
      growth and nitrate uptake and utilization, which are energy-expensive processes.

PMID- 25943354
TI  - Inferior thyroid artery pseudoaneurysm associated with internal jugular vein
      puncture: a case report.
AB  - BACKGROUND: Central venous catheter placement is an important aspect of patient
      care for the administration of fluids and medications and for monitoring
      purposes. However, it is still associated with significant morbidity and
      mortality. CASE PRESENTATION: We report a case of iatrogenic inferior thyroid
      artery pseudoaneurysm during the central line placement due to internal jugular
      vein puncture. This is a rare complication of central venous cannulation.
      Fortunately the pseudoaneurysm was monitored closely, diagnosed promptly and
      obliterated by using radiological intervention. We discuss the risk factors and
      management of the unintended artery puncture. CONCLUSION: The pathway of the
      management post arterial puncture depends on the size of the needle or catheter,
      which is direct related to the consequence of arterial injuries. Identifying risk
      factors is very important to avoid the complications. However, the use of
      ultrasound guided venipuncture is the most important method to avoid mechanical
      complications.

PMID- 25943355
TI  - Use of mechanical airway clearance devices in the home by people with
      neuromuscular disorders: effects on health service use and lifestyle benefits.
AB  - BACKGROUND: People with neuromuscular disorders (NMD) exhibit weak coughs and are
      susceptible to recurrent chest infections and acute respiratory complications,
      the most frequent reasons for their unplanned hospital admissions. Mechanical
      insufflation-exsufflation (MI-E) devices are a non-invasive method of increasing
      peak cough flow, improving cough efficacy, the clearance of secretion and
      overcoming atelectasis. There is limited published evidence on the impact of home
      use MI-E devices on health service utilisation. The aims of the study were: to
      assess the self-reported health and lifestyle benefits experienced as a result of
      home use of MI-E devices; and evaluate the effects of in-home use of MI-E devices
      on Emergency Department (ED) presentations, hospital admissions and inpatient
      length of stay (LOS). METHODS: Individuals with NMD who were accessing a home MI
      E device provided through Muscular Dystrophy Western Australia were invited to
      participate in a quantitative survey to obtain information on their experiences
      and self-assessed changes in respiratory health. An ad-hoc record linkage was
      performed to extract hospital, ED and mortality data from the Western Australian
      Department of Health (DOHWA). The main outcome measures were ED presentations,
      hospital separations and LOS, before and after commencement of home use of an MI
      E device. RESULTS: Thirty seven individuals with NMD using a MI-E device at home
      consented to participate in this study. The majority (73%) of participants
      reported using the MI-E device daily or weekly at home without medical assistance
      and 32% had used the machine to resolve a choking episode. The survey highlighted
      benefits to respiratory function maintenance and the ability to manage increased
      health care needs at home. Not using a home MI-E device was associated with an
      increased risk of ED presentations (RR = 1.76, 95% CI 1.1-2.84). The number of
      hospital separations and LOS reduced after the use of MI-E device, but not
      significantly. No deaths were observed in participants using the MI-E device at
      home. CONCLUSIONS: Home use of a MI-E device by people living with NMD may have a
      potential impact on reducing their health service utilisation and risk of death.
      Future research with greater subject numbers and longer follow-up periods is
      recommended to enhance this field of study.

PMID- 25943356
TI  - Myositis ossificans occupying the thenar region: a case report.
AB  - INTRODUCTION: Myositis ossificans is a benign, self-limiting, tumor-like lesion
      that usually affects the elbow and thigh; occurrence in the hand is uncommon. We
      report a rare case of a patient with myositis ossificans in the thenar region.
      CASE PRESENTATION: A 15-year-old Japanese girl presented to our hospital with a 2
      month history of a painful mass in the right thenar region without previous
      trauma. The clinical and radiological examination findings suggested an
      osteoblastic malignancy. A diagnosis of myositis ossificans was made on the basis
      of an incisional biopsy. Despite the location of the lesion in the thenar region,
      a normal functional outcome was achieved after marginal resection of the mature
      lesion. CONCLUSIONS: Clinicians should consider myositis ossificans as a possible
      diagnosis for a soft tissue mass in the hand, thereby avoiding unnecessarily
      aggressive therapy.

PMID- 25943357
TI  - Development of genetically engineered iNKT cells expressing TCRs specific for the
      M. tuberculosis 38-kDa antigen.
AB  - INTRODUCTION: The invariant natural killer T (iNKT) cell has been shown to play a
      central role in early stages immune responses against Mycobacterium tuberculosis
      (Mtb) infection, which become nonresponsive (anergic) and fails to control the
      growth of Mtb in patients with active tuberculosis. Enhancement of iNKT cell
      responses to Mtb antigens can help to resist infection. STUDY DESIGN AND METHODS:
      In the present study, an Mtb 38-kDa antigen-specific T cell receptor (TCR) was
      isolated from human CD8(+) T cells stimulated by 38-kDa antigen in vitro, and
      then transduced into primary iNKT cells by retrovirus vector. RESULTS: The TCR
      gene-modified iNKT cells are endowed with new features to behave as a
      conventional MHC class I restricted CD8(+) T lymphocyte by displaying specific
      antigen recognition and anti-Mtb antigen activity in vitro. At the same time, the
      engineered iNKT cells retaining its original capacity to be stimulated
      proliferation by non-protein antigens alpha-Gal-Cer. CONCLUSIONS: This work is
      the first attempt to engineer iNKT cells by exogenous TCR genes and demonstrated
      that iNKT cell, as well as CD4(+) and CD8(+) T cells, can be genetically
      engineered to confer them a defined and alternative specificity, which provides
      new insights into TCR gene therapy for tuberculosis patients, especially those
      infected with drug-resistant Mtb.

PMID- 25943358
TI  - Use of cassette dosing to enhance the throughput of rat brain microdialysis
      studies.
AB  - This study was designed to increase the throughput of rat brain microdialysis
      studies by administration of compounds as a cassette as opposed to discrete
      study. Eight compounds (carbamazepine, citalopram, desmethylclozapine,
      diphenhydramine, gabapentin, metoclopramide, naltrexone, and stavudine) were
      selected and administered as an intravenous bolus dose at 0.5-3.3 mg/kg each
      followed by an intravenous infusion at 1 mg/kg per hour for 6 hours in rats in a
      cassette or discrete dosing. The dialysate, plasma, brain, and cerebrospinal
      fluid were collected and analyzed using liquid chromatography-tandem mass
      spectrometry. The microdialysis probe recovery was determined by an in vitro gain
      method. The recovery between the cassette and discrete dosing was similar, with
      an average of 1.0 +/- 0.10-fold difference. The stavudine interstitial fluid
      (ISF) concentration, as measured by brain microdialysis, was below the low limit
      of quantitation and was excluded from the analyses. The ratios of ISF
      concentration to unbound plasma concentration were within 2-fold for six of the
      remaining seven compounds, with an average of 0.92 +/- 0.51-fold difference
      between the cassette and discrete methods. The ratios of ISF concentration to
      unbound brain concentration, as measured by the brain homogenate method, were
      also similar, with a 1.1 +/- 0.7-fold difference. In addition, the ratios of ISF
      to cerebrospinal fluid concentrations were similar, with a 1.5 +/- 0.6-fold
      difference. The results from this study support the use of a cassette dosing
      approach to enhance the throughput of rat brain microdialysis studies in drug
      discovery. 

PMID- 25943359
TI  - Pathologic manifestations of levamisole-adulterated cocaine exposure.
AB  - Rheumatic manifestations of cocaine have been well described, but more recently,
      a dramatic increase in the levamisole-adulterated cocaine supply in the United
      States has disclosed unique pathologic consequences that are distinct from pure
      cocaine use. Most notably, patients show skin lesions and renal dysfunction in
      the setting of extremely high perinuclear anti-neutrophil cytoplasmic antibodies
      (p-ANCA). Unexpectedly, antibodies to myeloperoxidase, the typical target of p
      ANCA, are relatively low if at all present. This discrepancy is due to the fact
      that p-ANCA seen in association with levamisole-adulterated cocaine exposure is
      often directed against atypical p-ANCA-associated antigens within the neutrophil
      granules such as human neutrophil elastase, lactoferrin, and cathepsin G.
      Biopsies of the skin lesions reveal leukocytoclastic vasculitis often involving
      both superficial and deep dermal vessels. Renal injury most typically manifests
      as crescentic and necrotizing pauci-immune glomerulonephritis. In this review,
      the manifestations of levamisole-adulterated cocaine-induced vasculitis are
      discussed with an emphasis on the typical histomorphologic findings seen on
      biopsy. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1764738711370019 .

PMID- 25943360
TI  - Ringer's lactate, but not hydroxyethyl starch, prolongs the food intolerance time
      after major abdominal surgery; an open-labelled clinical trial.
AB  - BACKGROUND: The infusion of large amounts of Ringer's lactate prolongs the
      functional gastrointestinal recovery time and increases the number of
      complications after open abdominal surgery. We performed an open-labelled
      clinical trial to determine whether hydroxyethyl starch or Ringer's lactate
      exerts these adverse effects when the surgery is performed by laparoscopy.
      METHODS: Eighty-eight patients scheduled for major abdominal cancer surgery (83%
      by laparoscopy) received a first-line fluid treatment with 9 ml/kg of either 6%
      hydroxyethyl starch 130/0.4 (Voluven) or Ringer's lactate, just after induction
      of anaesthesia; this was followed by a second-line infusion with 12 ml/kg of
      either starch or Ringer's lactate over 1 hour. Further therapy was managed at the
      discretion of the attending anaesthetist. Outcome data consisted of postoperative
      gastrointestinal recovery time, complications and length of hospital stay.
      RESULTS: The order of the infusions had no impact on the outcome. Both the
      administration of >= 2 L of Ringer's lactate and the development of a surgical
      complication were associated with a longer time period of paralytic ileus and
      food intolerance (two-way ANOVA, P < 0.02), but only surgical complications
      prolonged the length of hospital stay (P < 0.001). The independent effect of
      Ringer's lactate and complications of food intolerance time amounted to 2 days
      each. The infusion of >= 1 L of hydroxyethyl starch did not adversely affect
      gastrointestinal recovery. CONCLUSIONS: Ringer's lactate, but not hydroxyethyl
      starch, prolonged the gastrointestinal recovery time in patients undergoing
      laparoscopic cancer surgery. Surgical complications prolonged the hospital stay.

PMID- 25943361
TI  - Comparative genome analysis of rice-pathogenic Burkholderia provides insight into
      capacity to adapt to different environments and hosts.
AB  - BACKGROUND: In addition to human and animal diseases, bacteria of the genus
      Burkholderia can cause plant diseases. The representative species of rice
      pathogenic Burkholderia are Burkholderia glumae, B. gladioli, and B. plantarii,
      which primarily cause grain rot, sheath rot, and seedling blight, respectively,
      resulting in severe reductions in rice production. Though Burkholderia rice
      pathogens cause problems in rice-growing countries, comprehensive studies of
      these rice-pathogenic species aiming to control Burkholderia-mediated diseases
      are only in the early stages. RESULTS: We first sequenced the complete genome of
      B. plantarii ATCC 43733T. Second, we conducted comparative analysis of the newly
      sequenced B. plantarii ATCC 43733T genome with eleven complete or draft genomes
      of B. glumae and B. gladioli strains. Furthermore, we compared the genome of
      three rice Burkholderia pathogens with those of other Burkholderia species such
      as those found in environmental habitats and those known as animal/human
      pathogens. These B. glumae, B. gladioli, and B. plantarii strains have unique
      genes involved in toxoflavin or tropolone toxin production and the clustered
      regularly interspaced short palindromic repeats (CRISPR)-mediated bacterial
      immune system. Although the genome of B. plantarii ATCC 43733T has many common
      features with those of B. glumae and B. gladioli, this B. plantarii strain has
      several unique features, including quorum sensing and CRISPR/CRISPR-associated
      protein (Cas) systems. CONCLUSIONS: The complete genome sequence of B. plantarii
      ATCC 43733T and publicly available genomes of B. glumae BGR1 and B. gladioli BSR3
      enabled comprehensive comparative genome analyses among three rice-pathogenic
      Burkholderia species responsible for tissue rotting and seedling blight. Our
      results suggest that B. glumae has evolved rapidly, or has undergone rapid genome
      rearrangements or deletions, in response to the hosts. It also, clarifies the
      unique features of rice pathogenic Burkholderia species relative to other animal
      and human Burkholderia species.

PMID- 25943362
TI  - Vitamin D status in Saudi school children based on knowledge.
AB  - BACKGROUND: The prevalence of vitamin D deficiency in the kingdom of Saudi Arabia
      is rising unexpectedly in every age group. Apart from several risk factors, the
      lack of awareness is posing a serious threat for low vitamin D levels in children
      as well. The aim of our study was to compare the knowledge and status of vitamin
      D in Saudi school children. METHODS: Saudi students, 1188 boys (15.1 +/- 2.2
      years) and 1038 girls (15.1 +/- 2.0 years), were recruited and a pre-designed
      questionnaire with regards to knowledge about vitamin D was administered. Blood
      samples were collected and serum 25hydroxyvitamin D (25(OH)D was measured.
      RESULTS: A significantly higher percentage of boys answered correctly than girls
      regarding knowledge questions as sun exposure (p = 0.002, and 0.011),
      breastfeeding (p < 0.001) and diseases (p < 0.001). The percentage of girls was
      significantly higher who thought that fruits and vegetables are not rich sources
      of vitamin D (24.7% girls vs. 15.4% boys; p < 0.001and 29.6% girls vs. 20.9% boys
      p < 0.001), respectively. Boys had a higher prevalence and frequency of sun
      exposure than girls (p < 0.001 for both). Girls showed a significantly higher
      percentage of sunscreen use and full covering during sun exposure (p = 0.001 for
      both).Vitamin D deficiency was significantly higher in girls than boys (47.0%
      versus 19.4.0%; p < 0.001). Vitamin D status in boys was significantly higher
      than girls (p < 0.001). In girls, those who answered correctly about vitamin D
      related disease (p = 0.03) and sources (p = 0.015), demonstrated significantly
      higher vitamin D levels. CONCLUSIONS: The awareness of vitamin D and sunlight in
      children needs to be improved by provision of trained physicians and school
      teachers. Creating more areas where girls can uncover freely during routine works
      and outdoor activities will help increase their vitamin D levels.

PMID- 25943363
TI  - Marked improvement in autoimmune pulmonary alveolar proteinosis with severe
      hypoxemia in a patient treated with ambroxol: a case report.
AB  - INTRODUCTION: Pulmonary alveolar proteinosis is characterized by accumulation of
      surfactant and phospholipids in the pulmonary alveoli. Whole lung lavage is
      considered the first-line therapy, which requires special techniques. To the best
      of our knowledge, there have only been limited reports that have demonstrated the
      effectiveness of ambroxol on a mild case of pulmonary alveolar proteinosis. CASE
      PRESENTATION: A 72-year-old Japanese woman presented to our hospital with a one
      year history of productive cough and progressive dyspnea. Her chest computed
      tomography scan showed a bilateral crazy-paving pattern in both of her lungs. She
      was diagnosed with autoimmune pulmonary alveolar proteinosis based on
      bronchoalveolar lavage findings and the presence of serum anti-granulocyte
      macrophage colony-stimulating factor antibodies. She was severely hypoxemic, so
      we recommended whole lung lavage or inhaled granulocyte macrophage colony
      stimulating factor treatment, which she refused. We initiated treatment with
      ambroxol and her symptoms markedly improved. CONCLUSIONS: Although whole lung
      lavage is the first-line therapy for pulmonary alveolar proteinosis, oral
      ambroxol could be an alternative treatment option, even in patients with severe
      respiratory compromise.

PMID- 25943364
TI  - Gender Differences in the Routine Activities Associated With Risks for Larceny in
      South Korea.
AB  - The present research uses data from the 2010 Korean National Criminal
      Victimization Survey to examine gender differences in larceny victimization and
      in predictors of victimization (i.e., target attractiveness, exposure to
      potential offenders, target hardening, guardianship, and proximity to crime and
      social disorder) identified by routine activity theory. The findings show no
      significant gender difference in general larceny victimization, suggesting that
      Korean females are just as likely to be victims of theft of personal belongings
      as males. Consistent with the theory, physical proximity to crime and social
      disorder are significant predictors of larceny victimization for both males and
      females. However, public transportation appears to have unexpected protective
      influences for both gender groups, showing the importance of differences in
      national context. Overall, the current research provides partial support for
      routine activity theory's applicability in explaining larceny victimization
      across gender groups outside of the Western context. It also raises questions
      about reasons for women's increasing larceny victimization rates in Korea. 

PMID- 25943365
TI  - Parental Low Self-Control, Family Environments, and Juvenile Delinquency.
AB  - Research consistently finds that low self-control is significantly correlated
      with delinquency. Only recently, however, have researchers started to examine
      associations between parental low self-control, family environments, and child
      antisocial behavior. Adding to this emerging area of research, the current study
      examines associations between parental low self-control, aspects of the family
      environment, and officially recoded juvenile delinquency among a sample (N = 101)
      of juveniles processed through a juvenile justice assessment facility located in
      the Southeastern United States. Furthermore, it considers whether aspects of
      family environments, particularly family cohesion, family conflict, and parental
      efficacy, mediate the influence of parental low self-control on delinquency. The
      results of a series of analyses indicate that parental low self-control is
      correlated with various aspects of family environments and juvenile delinquency,
      and that the association between parental low self-control and juvenile
      delinquency is mediated by family environments. Supplementary analyses also
      suggest that the association between parental low self-control and the family
      environment may be reciprocal. 

PMID- 25943366
TI  - A General Method of Empirical Q-matrix Validation.
AB  - In contrast to unidimensional item response models that postulate a single
      underlying proficiency, cognitive diagnosis models (CDMs) posit multiple,
      discrete skills or attributes, thus allowing CDMs to provide a finer-grained
      assessment of examinees' test performance. A common component of CDMs for
      specifying the attributes required for each item is the Q-matrix. Although
      construction of Q-matrix is typically performed by domain experts, it
      nonetheless, to a large extent, remains a subjective process, and
      misspecifications in the Q-matrix, if left unchecked, can have important
      practical implications. To address this concern, this paper proposes a
      discrimination index that can be used with a wide class of CDM subsumed by the
      generalized deterministic input, noisy "and" gate model to empirically validate
      the Q-matrix specifications by identifying and replacing misspecified entries in
      the Q-matrix. The rationale for using the index as the basis for a proposed
      validation method is provided in the form of mathematical proofs to several
      relevant lemmas and a theorem. The feasibility of the proposed method was
      examined using simulated data generated under various conditions. The proposed
      method is illustrated using fraction subtraction data.

PMID- 25943367
TI  - Organization and evaluation of generalist palliative care in a Danish hospital.
AB  - BACKGROUND: Hospitals have a responsibility to ensure that palliative care is
      provided to all patients with life-threatening illnesses. Generalist palliative
      care should therefore be acknowledged and organized as a part of the clinical
      tasks. However, little is known about the organization and evaluation of
      generalist palliative care in hospitals. Therefore the aim of the study was to
      investigate the organization and evaluation of generalist palliative care in a
      large regional hospital by comparing results from existing evaluations. METHODS:
      Results from three different data sets, all aiming to evaluate generalist
      palliative care, were compared retrospectively. The data-sets derived from; 1. a
      national accreditation of the hospital, 2. a national survey and 3. an internal
      self-evaluation performed in the hospital. The data were triangulated to
      investigate the organization and evaluation of palliative care in order to
      identify concordances and/or discrepancies. RESULTS: The triangulation indicated
      poor validity of the results from existing methods used to evaluate palliative
      care in hospitals. When the datasets were compared, several discrepancies
      occurred with regard to the organization and the performance of generalist
      palliative care. Five types of discrepancies were found in 35 out of 56 sections
      in the fulfilment of the national accreditation standard for palliative care.
      Responses from the hospital management and the department managements indicated
      that generalist palliative care was organized locally--if at all--within the
      various departments and with no overall structure or policy. CONCLUSIONS: This
      study demonstrates weaknesses in the existing evaluation methods for generalist
      palliative care and highlights the lack of an overall policy, organization and
      goals for the provision of palliative care in the hospital. More research is
      needed to focus on the organization of palliative care and to establish
      indicators for high quality palliative care provided by the hospital. The lack of
      valid indicators, both for the hospital's and the departments' provision of
      palliative care, calls for more qualitative insight in the clinical staff's daily
      work including their culture and acceptance of the provision of palliative care.

PMID- 25943368
TI  - Ceruloplasmin activity and iron chelation treatment of patients with Parkinson's
      disease.
AB  - BACKGROUND: Growing body of evidence suggests that Parkinson's disease (PD) is
      associated with oxidative damage via iron accumulation in the substantia nigra
      (SN). Low ceruloplasmin (CP)-ferroxidase activity has been identified in the SN
      and the cerebrospinal fluid (CSF) of patients with PD. The iron chelator,
      deferiprone, reduces the abnormally high levels of iron in the SN. In order to
      determine CP's involvement in iron accumulation in SN and PD progression, we aim
      to compare the ability of iron chelation treatment to reducing both SN iron
      levels and motor handicap in PD patients according to the level of ceruloplasmin
      activity. METHODS: We used a moderate chelation protocol with deferiprone (DFP)
      based on a, 6-month delayed-start paradigm, randomized placebo controlled
      clinical trial in 40 PD patients. CP-ferroxidase activity was determined in blood
      and CSF together with the D544E gene polymorphism (rs701753). Iron levels were
      determined by R2* MRI sequence and the motor handicap by the UPDRS motor score.
      RESULTS: After 6 to 12 months of DFP treatment, greater reductions in SN iron
      levels and UPDRS motor scores were obtained in patients with higher serum and CSF
      levels of CP-ferroxidase activity. After 6 months of DFP treatment, the AT
      genotype group displayed greater reduction of iron level in the SN with greater
      CSF and serum levels of CP activity than the AA genotype group. CONCLUSION:
      Although most of the DFP-treated patients displayed clinical and radiological
      improvements, those with the lower CP activity appeared to respond better to iron
      chelation. Larger RCTs are now needed to establish whether pharmacological
      modulation of CP activity could be an innovative neuroprotective strategy in PD.
      TRIAL REGISTRATION: FAIR-PARK study (ClinicalTrials.gov reference: NCT00943748 ;
      French national reference number: 2008-006842-25). This study was approved by the
      French Drug Agency (ANSM) and the local institutional review board ("Comite de
      Protection des Personnes of Lille").

PMID- 25943369
TI  - Field phenotyping of grapevine growth using dense stereo reconstruction.
AB  - BACKGROUND: The demand for high-throughput and objective phenotyping in plant
      research has been increasing during the last years due to large experimental
      sites. Sensor-based, non-invasive and automated processes are needed to overcome
      the phenotypic bottleneck, which limits data volumes on account of manual
      evaluations. A major challenge for sensor-based phenotyping in vineyards is the
      distinction between the grapevine in the foreground and the field in the
      background - this is especially the case for red-green-blue (RGB) images, where
      similar color distributions occur both in the foreground plant and in the field
      and background plants. However, RGB cameras are a suitable tool in the field
      because they provide high-resolution data at fast acquisition rates with
      robustness to outdoor illumination. RESULTS: This study presents a method to
      segment the phenotypic classes 'leaf', 'stem', 'grape' and 'background' in RGB
      images that were taken with a standard consumer camera in vineyards. Background
      subtraction is achieved by taking two images of each plant for depth
      reconstruction. The color information is furthermore used to distinguish the
      leaves from stem and grapes in the foreground. The presented approach allows for
      objective computation of phenotypic traits like 3D leaf surface areas and fruit
      to-leaf ratios. The method has been successfully applied to objective assessment
      of growth habits of new breeding lines. To this end, leaf areas of two breeding
      lines were monitored and compared with traditional cultivars. A statistical
      analysis of the method shows a significant (p <0.001) determination coefficient R
      (2)= 0.93 and root-mean-square error of 3.0%. CONCLUSIONS: The presented approach
      allows for non-invasive, fast and objective assessment of plant growth. The main
      contributions of this study are 1) the robust segmentation of RGB images taken
      from a standard consumer camera directly in the field, 2) in particular, the
      robust background subtraction via reconstruction of dense depth maps, and 3)
      phenotypic applications to monitoring of plant growth and computation of fruit-to
      leaf ratios in 3D. This advance provides a promising tool for high-throughput,
      automated image acquisition, e.g., for field robots.

PMID- 25943370
TI  - The cost-effectiveness of initiating ranibizumab therapy in eyes with neovascular
      AMD with good vision: an economic model using real-world outcomes.
AB  - OBJECTIVES: To evaluate the cost-effectiveness of immediate treatment with
      ranibizumab in patients with neovascular age-related macular degeneration (nAMD)
      with good (better than 6/12) starting visual acuity compared with current UK
      clinical guidance of waiting until vision falls below 6/12 to begin treatment,
      using real-world outcomes data. DESIGN: A patient-level health economic state
      transition model based on levels of visual acuity in the better seeing eye was
      constructed to simulate the costs and consequences of treating patients with nAMD
      with ranibizumab. SETTING: The model took the perspective of the UK National
      Health Service (NHS). PARTICIPANTS: The model was populated with real-world
      outcomes and resource use from a prospective multicentre national nAMD database
      study containing 92,976 ranibizumab treatment episodes. INTERVENTIONS: Two
      treatment approaches were compared: immediate intervention with 0.5 mg
      ranibizumab pro re nata, PRN (on detection of nAMD) or delayed intervention
      (waiting until vision fell to 6/12 before beginning treatment). MAIN OUTCOME
      MEASURES: Quality-adjusted life years (QALYs) for health states and healthcare
      costs were accrued for each strategy, and an incremental cost-effectiveness ratio
      (ICER) was calculated. One-way and probabilistic sensitivity analyses were
      employed to test the uncertainty of the model. RESULTS: Over a 2-year time
      horizon, based on 10,000 Monte Carlo simulations, the early treatment arm
      accumulated 1.59 QALYs and L8469.79 cost. The delayed treatment arm accumulated
      1.35 QALYs and L7460.21 cost. The central ICER estimate was L4251.60.
      CONCLUSIONS: A model based on real-world data is likely to be a realistic
      reflection of the health gains and resource use of ranibizumab for nAMD in the UK
      NHS. Initiating treatment immediately with ranibizumab PRN regimen is a cost
      effective strategy compared with current guidance of initiating treatment at a
      level of 6/12 or worse vision.

PMID- 25943371
TI  - Evidence-informed recommendations to reduce dissemination bias in clinical
      research: conclusions from the OPEN (Overcome failure to Publish nEgative
      fiNdings) project based on an international consensus meeting.
AB  - BACKGROUND: Dissemination bias in clinical research severely impedes informed
      decision-making not only for healthcare professionals and patients, but also for
      funders, research ethics committees, regulatory bodies and other stakeholder
      groups that make health-related decisions. Decisions based on incomplete and
      biased evidence cannot only harm people, but may also have huge financial
      implications by wasting resources on ineffective or harmful diagnostic and
      therapeutic measures, and unnecessary research. Owing to involvement of multiple
      stakeholders, it remains easy for any single group to assign responsibility for
      resolving the problem to others. OBJECTIVE: To develop evidence-informed general
      and targeted recommendations addressing the various stakeholders involved in
      knowledge generation and dissemination to help overcome the problem of
      dissemination bias on the basis of previously collated evidence. METHODS: Based
      on findings from systematic reviews, document analyses and surveys, we developed
      general and targeted draft recommendations. During a 2-day workshop in summer
      2013, these draft recommendations were discussed with external experts and key
      stakeholders, and refined following a rigorous and transparent methodological
      approach. RESULTS: Four general, overarching recommendations applicable to all or
      most stakeholder groups were formulated, addressing (1) awareness raising, (2)
      implementation of targeted recommendations, (3) trial registration and results
      posting, and (4) systematic approaches to evidence synthesis. These general
      recommendations are complemented and specified by 47 targeted recommendations
      tailored towards funding agencies, pharmaceutical and device companies, research
      institutions, researchers (systematic reviewers and trialists), research ethics
      committees, trial registries, journal editors and publishers, regulatory
      agencies, benefit (health technology) assessment institutions and legislators.
      CONCLUSIONS: Despite various recent examples of dissemination bias and several
      initiatives to reduce it, the problem of dissemination bias has not been
      resolved. Tailored recommendations based on a comprehensive approach will
      hopefully help increase transparency in biomedical research by overcoming the
      failure to disseminate negative findings.

PMID- 25943372
TI  - Who is in control? Clinicians' view on their role in self-management approaches:
      a qualitative metasynthesis.
AB  - OBJECTIVE: To explore clinician perceptions of involvement in delivery of self
      management approaches. SETTING: All healthcare settings. DESIGN: EBSCO, Scopus
      and AMED databases were searched, in July 2013, for peer-reviewed studies in
      English reporting original qualitative data concerning perceptions of clinicians
      regarding their involvement in or integration of a self-management approach. Of
      1930 studies identified, 1889 did not meet the inclusion criteria. Full text of
      41 studies were reviewed by two independent reviewers; 14 papers were included
      for metasynthesis. Findings and discussion sections were imported into Nvivo-10
      and coded line-by-line. Codes were organised into descriptive themes and cross
      checked against original sources to check interpretation, and refined iteratively
      until findings represented an agreed understanding. Studies were appraised for
      quality. RESULTS: Delivering self-management in practice appeared to be a complex
      process for many clinicians. The issue of 'control' arose in all studies, both in
      the qualitative data and authors' interpretations. The first theme: Who is in
      control?--represented ways clinicians talked of exercising control over patients
      and the control they expected patients to have over their condition. The second
      theme: Changing clinician views--reflected what appeared to be an essential
      transformation of practice experienced by some clinicians in the process of
      integrating self-management approaches into the practice. A range of challenges
      associated with shifting towards a self-management approach were reflected in the
      third theme, Overcoming challenges to change. Tensions appeared to exist around
      forming partnerships with patients. Strategies found helpful in the process of
      change included: dedicating time to practice reciprocity in communication style,
      peer support and self-reflection. CONCLUSIONS: A consistent finding across
      studies is that 'control' is a key feature of how self-management is viewed by
      clinicians. They described challenges associated with the paradigm shift required
      to share or let go of control. Future research should identify whether strategies
      described by clinicians are key to successful self-management.

PMID- 25943373
TI  - Development of LNA oligonucleotide-PCR clamping technique in investigating the
      community structures of plant-associated bacteria.
AB  - Simultaneous extraction of plant organelle (mitochondria and plastid) genes
      during the DNA extraction step is major limitation in investigating the community
      structures of plant-associated bacteria. Although locked nucleic acid (LNA)
      oligonucleotides was designed to selectively amplify the bacterial small subunit
      rRNA genes by applying the PCR clamping technique, those for plastids were
      applicable only for particular plants, while those for mitochondria were
      available throughout most plants. To widen the applicable range, new LNA
      oligonucleotides specific for plastids were designed, and the efficacy was
      investigated. PCR without LNA oligonucleotides predominantly amplified the
      organelle genes, while bacterial genes were predominantly observed in having
      applied the LNA oligonucleotides. Denaturing gradient gel electrophoresis (DGGE)
      analysis displayed additional bacterial DGGE bands, the amplicons of which were
      prepared using the LNA oligonucleotides. Thus, new designed LNA oligonucleotides
      specific for plastids were effective and have widened the scope in investigating
      the community structures of plant-associated bacteria. 

PMID- 25943374
TI  - Lithotomy versus jack-knife position on haemodynamic parameters assessed by
      impedance cardiography during anorectal surgery under low dose spinal
      anaesthesia: a randomized controlled trial.
AB  - BACKGROUND: Although the prone position providing better exposure for anorectal
      surgery is required it can cause a reduction of cardiac output and cardiac index.
      The goal was to compare haemodynamic changes assessed by impedance cardiography
      during anorectal surgery under low-dose spinal anaesthesia in lithotomy and jack
      knife position. METHODS: The prospective randomized controlled study included
      104, ASA I-II adult patients admitted for elective minor anorectal surgery,
      assigned to be performed in lithotomy (groupL, n = 52) or jack-knife position
      (groupJ, n = 52). After arrival to operating room the standard monitoring,
      impedance cardiography device was connected to the patient, and the following
      variables were recorded: cardiac output, cardiac index, systemic vascular
      resistance, stroke index at times of arrival to operating room, placement for,
      start and end of surgery and placement to bed. Spinal block was made in the
      sitting position with 4 mg of 0.5% hyperbaric bupivacaine and 10 MUg of Fentanyl
      injected over 2 min. Comparison was based on haemodynamic changes between and
      inside groups over time. Student's t, chi square tests were used for statistical
      analysis with p < 0.05 regarded as statistically significant. RESULTS: The
      reduction of cardiac output was statistically significant after placement of the
      patient into the prone position: from baseline 7.4+/-1.6 to 4.9+/-1.2 after
      placement for and 4.7+/-1.2 at the start and end of surgery (mean +/-SD l/min).
      The difference of cardiac output between groups was 2.0 l/min after positioning
      for and the start of surgery and 1.5 l/min at the end of surgery (p < 0.05). Mean
      cardiac index reduced from baseline 3.9+/-0.8 to 2.6+/-0.7 and 2.4+/-0.6 (mean+/
      SD l/min/m(2)) in groupJ and between groups: by 1.0 l/min/m(2) after placement
      for, 1.1 at the start and 0.8 at the end of surgery (p < 0.05). Systemic vascular
      resistance increased from baseline 1080+/-338 to 1483+/-479 after placement for,
      1523+/-481 at the start and 1525+/-545 at the end of surgery in groupJ (mean+/-SD
      dynes/sec/cm(-5), p < 0.05). CONCLUSIONS: According to impedance cardiography,
      jack-knife position after low-dose spinal anaesthesia produces transitory, but
      statistically significant reduction of cardiac output and cardiac index with
      increase of systemic vascular resistance, compared to insignificant changes in
      lithotomy position. TRIAL REGISTRATION: Clinical Trials NCT02115178.

PMID- 25943375
TI  - Structural transitions of centromeric chromatin regulate the cell cycle-dependent
      recruitment of CENP-N.
AB  - Specific recognition of centromere-specific histone variant CENP-A-containing
      chromatin by CENP-N is an essential process in the assembly of the kinetochore
      complex at centromeres prior to mammalian cell division. However, the mechanisms
      of CENP-N recruitment to centromeres/kinetochores remain unknown. Here, we show
      that a CENP-A-specific RG loop (Arg80/Gly81) plays an essential and dual
      regulatory role in this process. The RG loop assists the formation of a compact
      "ladder-like" structure of CENP-A chromatin, concealing the loop and thus
      impairing its role in recruiting CENP-N. Upon G1/S-phase transition, however,
      centromeric chromatin switches from the compact to an open state, enabling the
      now exposed RG loop to recruit CENP-N prior to cell division. Our results provide
      the first insights into the mechanisms by which the recruitment of CENP-N is
      regulated by the structural transitions between compaction and relaxation of
      centromeric chromatin during the cell cycle. 

PMID- 25943376
TI  - Unilateral horizontal semicircular canal occlusion induces serotonin increase in
      medial vestibular nuclei: a study using microdialysis in vivo coupled with HPLC
      ECD.
AB  - Unilateral single semicircular canal occlusion (USSCO) is an effective treatment
      for some cases of intractable vertigo. All patients suffer behavioural imbalance
      caused by surgery, and then recover with a resumption of vestibular function.
      However, the compensation mechanism has not been fully evaluated. Findings
      suggest that serotonin (5-HT) is released from nerve terminals, and plays a vital
      role in the plasticity of the central nervous system. In this study, we performed
      surgery of unilateral single semicircular canal occlusion (USSCO) on guinea pigs,
      and investigated the change of 5-HT by in vivo microdialysis of the medial
      vestibular nucleus (MVN) coupled with high-performance liquid chromatography and
      electrochemical detection (HPLC-ECD). A total of 12 guinea pigs were divided
      randomly into two groups, namely the USSCO group and the control group. Animals
      in the USSCO group underwent surgery of lateral horizontal semicircular canal
      occlusion, and those in the control group experienced the same operation but just
      to expose the horizontal semicircular canal without occlusion. Vestibular
      disturbance symptoms were observed in the case of the USSCO group, e.g. head
      tilting, and forced circular movements and spontaneous nystagmus at postoperative
      days 1 and 3. The basal level of 5-HT was determined to be 316.78 +/- 16.62 nM.
      It elevated to 448.85 +/- 24.56 nM at one day following occlusion (P = 0.001).
      The increase was completely abolished with the vestibular dysfunction recovery.
      The results showed that unilateral horizontal semicircular canal occlusion could
      increase the 5-HT level in MVN. 5-HT may play a significant role in the process
      of central vestibular compensation with residual vestibular function. 

PMID- 25943377
TI  - Body composition among Sri Lankan infants by 18O dilution method and the validity
      of anthropometric equations to predict body fat against 18O dilution.
AB  - BACKGROUND: Body composition indicators provide a better guidance for growth and
      nutritional status of the infants. This study was designed to (1) measure the
      body composition of the Sri Lankan infants using a reference method, the (18)O
      dilution method; (2) calculate the body fat content of the infants using
      published skinfold prediction equations; and (3) evaluate the applicability of
      the skinfold equations to predict body fat among Sri Lankan infants against the
      (18)O dilution method. METHODS: Twenty five healthy, exclusively breast-fed
      infants were randomly recruited at well-baby clinics, for this cross-sectional
      study. Body composition was measured using (18)O dilution. Infant body weight,
      length, skinfold thicknesses and mid upper-arm circumference were measured using
      standard procedures. The Bland and Atlman pair-wise comparison method was used to
      evaluate the agreement of body fat generated using the anthropometric prediction
      equations against the (18)O dilution values as the reference. RESULTS: Mean (SD)
      body weight and length of the infants were 6.5 kg (0.9) and 64.7 cm (2.8)
      respectively. Mean total body water, fat free mass, fat mass and % fat mass as
      measured by (18)O dilution method were 58.8% (5.0), 4.6 kg (0.8), 1.9 (0.5) and
      29.5% (6.1). Total body water and fat free mass were significantly higher in boys
      when compared to girls. With the exception of three prediction equations (Bandana
      et al., Goran et al. and Durnin and Wormsley), most of the other commonly used
      anthropometry-based prediction equations yielded a bias which was not constant
      but a function of the % fat mass. CONCLUSIONS: Body composition of Sri Lankan
      infants is comparable to the normative data available from the industrialized
      countries. Most of the commonly used anthropometric prediction equations
      generated a bias which varies with the size of the body fat. Only three
      prediction equations (Bandana, Goran, Durnin & Wormsley) yield a constant bias.
      The Durnin & Wormsely equation showed the smallest bias when compared to the
      (18)O dilution values with the narrowest limits of agreement. Accuracy of some of
      the prediction equations is a function of gender.

PMID- 25943378
TI  - Rare non-traumatic periprosthetic femoral fracture with features of an atypical
      femoral fracture: a case report.
AB  - INTRODUCTION: Atypical femoral fractures have emerged as one of the potential
      complications of bisphosphonates during the past decade. The American Society for
      Bone and Mineral Research published a Task Force report on atypical femoral
      fractures in 2010 and a second report in 2014. Although the current definition of
      atypical femoral fractures in these reports excludes periprosthetic fractures,
      each of three published case reports describe a bisphosphonate-associated
      atypical femoral fracture that occurred around the stem of a total hip
      arthroplasty. We report a rare case of an atypical femoral fracture that occurred
      at the stem tip of a total hip arthroplasty that fulfills the major criteria
      defined by the second American Society for Bone and Mineral Research Task Force
      report for an atypical femoral fracture and that was associated with prolonged
      use of bisphosphonate. CASE PRESENTATION: A 69-year-old Japanese woman with a
      right cementless total hip arthroplasty undertaken 44 months previously had a
      right femoral shaft fracture that occurred without trauma. She related that the
      bone fractured while she was standing, after which she fell down. Radiographs
      showed a noncomminuted transverse fracture located at the tip of the stem with
      localized periosteal thickening of the lateral cortex. The fracture was complete,
      extending through both cortices, and was associated with a medial spike. Her
      history revealed that she had been taking prednisolone to treat dermatomyositis
      and interstitial pneumonia for approximately 15 years. Alendronate was
      administered for more than 7 years. We performed open reduction and internal
      fixation using a locking plate with cable grip. The latest follow-up was
      performed 2 years after the fracture surgery. Bony union was successful. She
      regained the ability to walk, although her activity was limited by her
      comorbidities. CONCLUSIONS: Although the current definition of an atypical
      femoral fracture excludes periprosthetic fractures, there may be a periprosthetic
      fracture with the same or similar pathology as that of an atypical femoral
      fracture. We must be vigilant and aware of this type of fracture, especially in
      patients with prolonged bisphosphonate use.

PMID- 25943379
TI  - High prevalence of dhfr and dhps molecular markers in Plasmodium falciparum in
      pregnant women of Nchelenge district, Northern Zambia.
AB  - BACKGROUND: Sulphadoxine-pyrimethamine (SP) is the recommended drug for
      intermittent preventive treatment in pregnancy (IPTp) in most African countries,
      including Zambia. However, malaria is still one of the leading causes of
      morbidity and mortality in pregnant women despite reports of greater than 50% of
      women taking at least two doses of SP in IPTp. Studies have shown that resistance
      to SP is associated with mutations in the dhfr and dhps gene of Plasmodium
      falciparum. This study examined the prevalence of dhfr and dhps polymorphisms in
      P. falciparum found in pregnant women of Nchelenge district. METHOD: This cross
      sectional study was conducted in 2013 in Nchelenge, a holoendemic area with
      malaria prevalence estimated at 50% throughout the year. Three rural health
      centres were randomly selected and a census survey carried out at each health
      centre. A questionnaire was administered and malaria testing done using RDT and
      microscopy, with collection of a dried blood spot. A chelex extraction was done
      to extract parasite DNA from dried blood spots followed by nested PCR and enzyme
      restriction digestion. RESULTS: Of the enrolled participants (n = 375), the
      median age of the women was 23. The prevalence of malaria by PCR was 22%. The PCR
      positive samples examined (n = 72) showed a high prevalence of dhfr triple (Asn
      108 + Arg-59 + Ile-59) mutant (68%) and dhps double (Gly -437 + Glu-540) mutant
      (21%). The quintuple haplotype was found in 17% with 2 samples with an additional
      Gly-581mutation. In addition 6% mutations at Val-16 were found and none found at
      Thr-108 respectively, these both confer resistance to cycloguanil. Multivariate
      analysis showed that there was an association between malaria and women aged 30
      34 years old p < 0.05(AOR: 0.36) at 95% CI. CONCLUSION: This study showed a high
      number of mutations in the dhfr and dhps genes. The high malaria endemicity in
      the general population of this area may have contributed to the high prevalence
      of resistant parasites in pregnant women, suggesting a need to examine the
      efficacy of SP given that it is the only approved drug for IPTp in Zambia.

PMID- 25943380
TI  - On aging and aged care in Serbia.
AB  - Serbia is a demographically old nation, with 17.4 % of its residents being aged
      65 years and older in 2011. The previous two decades of turbulent history have
      significantly affected the demographic picture of this country, and their
      ramifications remain visible in Serbia's economic, political, cultural, and
      health spheres. Major demographic forces behind population aging in Serbia can be
      attributed to lower fertility rates, migrations, and declining mortality
      (reflecting improvements in overall health leading to a longer life expectancy).
      In Serbia, low fertility and migrations appear to play major roles, although the
      relative contribution of recent migrations cannot be measured with accuracy.
      Patterns of demographic aging vary considerably across different geographic,
      socioeconomic, and cultural settings. The common denominator throughout present
      day Serbia is extensive political and economic transition. One would expect that,
      given sufficient time, this process will result in improved population health,
      and yet, at this stage outcomes of major health care reform in Serbia are
      somewhat perplexing. For the second consecutive year, Serbia's health care system
      has been ranked at the very bottom of the scale among 34 European countries. It
      is then no surprise that the elderly represent particularly vulnerable population
      segment. This paper discusses some of the issues relevant to these demographic
      patterns of aging and aged care in contemporary Serbia, focusing on the period
      after 2000.

PMID- 25943381
TI  - Grey-scale ultrasound findings of lower extremity entheses in healthy children.
AB  - BACKGROUND: To describe grey-scale sonographic findings in lower extremity
      entheses in healthy children. METHODS: Healthy patients referred to Orthopedic
      Surgery or Adolescent Medicine outpatient clinics or their siblings ages 5-18
      years were recruited. Grey-scale ultrasound was performed on 3 entheseal sites
      bilaterally, the proximal patellar ligament insertion (PPL), distal patellar
      ligament insertion (DPL), and Achilles tendon insertion (AT). Entheseal thickness
      and quality were recorded. Comparison of thickness between contralateral sites
      was evaluated to determine within subject site variability. RESULTS: 702 entheses
      were examined in 117 children. Age had a weak positive correlation with thickness
      with large variability. Weight had the strongest correlation to thickness.
      Contralateral sites are comparable in thickness; a difference of 28%, 26%, and
      18% between bilateral PPL, DPL, and AT, respectively, falls within the 95th
      percentile of the healthy pediatric population in this study. The patellar
      ligament contour evolved with age from a curved to linear contour. CONCLUSIONS:
      Weight is the best predictor of entheseal thickness in children although there is
      a large degree of variability. Contralateral entheses are comparable in
      thickness. A difference below 28%, 26%, and 18% between bilateral PPL, DPL, and
      AT, respectively, falls within the 95(th) percentile.

PMID- 25943382
TI  - Se-Methyl-L-selenocysteine Induces Apoptosis via Endoplasmic Reticulum Stress and
      the Death Receptor Pathway in Human Colon Adenocarcinoma COLO 205 Cells.
AB  - Selenomethionine (SeMet) and Se-methyl-L-selenocysteine (MSeC) are natural
      organoselenium compounds found in garlic, onion, and broccoli. In addition, these
      compounds have lower toxicity and better anticancer activities than inorganic Se.
      This study investigated the effects of MSeC treatment on the growth of COLO 205
      human colorectal adenocarcinoma cells and evaluated the mechanisms related to the
      MSeC-induced effects. When COLO 205 cells were treated with 200 MUM MSeC for 24
      h, MSeC caused 80% apoptosis in cells. MSeC increased the expression of Fas and
      FasL, followed by the cleavage of caspase-3, caspase-8, DNA fragmentation factor
      (DFF45), and poly(ADP-ribose) polymerase (PARP). MSeC also increased the levels
      of Bax protein and decreased the levels of Bid and Bcl-2 proteins. However, MSeC
      did not cause apoptosis through reactive oxygen species (ROS) stress but instead
      through endoplasmic reticulum (ER) stress. The cleavage of caspase-12 and caspase
      9 was shown to increase the growth arrest and protein levels of DNA-damage
      inducible genes (GADD) 153 and 45. MSeC also downregulated the ERK1/2 and
      PI3K/AKT protein levels and upregulated the p38 and JNK protein levels in COLO
      205 cells. These results showed that the mechanism by which MSeC induced
      apoptosis in COLO 205 cells involved caspase activation, the extrinsic apoptotic
      pathway, and the regulation of ER-stress-induced apoptosis.

PMID- 25943383
TI  - Efficient production of free fatty acids from soybean meal carbohydrates.
AB  - Conversion of biomass feedstock to chemicals and fuels has attracted increasing
      attention recently. Soybean meal, containing significant quantities of
      carbohydrates, is an inexpensive renewable feedstock. Glucose, galactose, and
      fructose can be obtained by enzymatic hydrolysis of soluble carbohydrates of
      soybean meal. Free fatty acids (FFAs) are valuable molecules that can be used as
      precursors for the production of fuels and other value-added chemicals. In this
      study, free fatty acids were produced by mutant Escherichia coli strains with
      plasmid pXZ18Z (carrying acyl-ACP thioesterase (TE) and (3R)-hydroxyacyl-ACP
      dehydratase) using individual sugars, sugar mixtures, and enzymatic hydrolyzed
      soybean meal extract. For individual sugar fermentations, strain ML211 (MG1655
      fadD(-) fabR(-) )/pXZ18Z showed the best performance, which produced 4.22, 3.79,
      3.49 g/L free fatty acids on glucose, fructose, and galactose, respectively.
      While the strain ML211/pXZ18Z performed the best with individual sugars, however,
      for sugar mixture fermentation, the triple mutant strain XZK211 (MG1655 fadD(-)
      fabR(-) ptsG(-) )/pXZ18Z with an additional deletion of ptsG encoding the glucose
      specific transporter, functioned the best due to relieved catabolite repression.
      This strain produced approximately 3.18 g/L of fatty acids with a yield of 0.22 g
      fatty acids/g total sugar. Maximum free fatty acids production of 2.78 g/L with a
      high yield of 0.21 g/g was achieved using soybean meal extract hydrolysate. The
      results suggested that soybean meal carbohydrates after enzymatic treatment could
      serve as an inexpensive feedstock for the efficient production of free fatty
      acids.

PMID- 25943384
TI  - Population pharmacokinetics of mycophenolic acid in lung transplant recipients
      with and without cystic fibrosis.
AB  - PURPOSE: The objective of this work was to characterize and compare the
      population pharmacokinetics (PK) mycophenolic acid (MPA) in adult lung transplant
      recipients with cystic fibrosis (CF) and without the disease (NCF) following
      repeated oral administration of the prodrug mycophenolate mofetil (MMF) as an
      immunosuppressant. METHODS: Three separate 12-h PK visits were conducted for lung
      transplant patients with or without CF following repeated MPA treatment with at
      least a 2-week break between the visits. A population PK model was developed
      using nonlinear mixed effects modeling (NONMEM), and the contribution of
      physiological and pathological factors and time dependence of apparent oral
      clearance (CL/F) were assessed. RESULTS: For both CF and NCF patients, MPA serum
      concentration-time profiles were best described by a two-compartment PK model
      with first-order absorption. CF patients had a slower absorption rate (Ka), and
      elevated CL/F and volume of distribution (Vd/F) compared with NCF patients. There
      is a significant contribution of body weight and CF disease to MPA CL/F, and both
      were included in the final model as covariates. CONCLUSIONS: The population PK
      model developed from our study successfully characterizes the absorption,
      distribution, and elimination of MPA in lung transplant recipients with or
      without CF disease. The decrease of MPA absorption and increase of both oral
      clearance (CL/F) and volume of distribution (V2/F and V3/F) in the CF patients
      would suggest the importance of MPA therapeutic monitoring for this group.

PMID- 25943385
TI  - Socioeconomic inequalities in smoking in The Netherlands before and during the
      Global Financial Crisis: a repeated cross-sectional study.
AB  - BACKGROUND: The Global Financial Crisis (GFC) increased levels of financial
      strain, especially in those of low socioeconomic status (SES). Financial strain
      can affect smoking behaviour. This study examines socioeconomic inequalities in
      current smoking and smoking cessation in The Netherlands before and during the
      Global Financial Crisis (GFC). METHODS: Participants were 66,960 Dutch adults (>=
      18 years) who took part in the annual national Health Survey (2004-2011). Period
      was dichotomised: 'pre-' and 'during-GFC'. SES measures used were income,
      education and neighbourhood deprivation. Outcomes were current smoking rates
      (smokers/total population) and smoking cessation ratios (former smokers/ever
      smokers). Multilevel logistic regression models controlled for individual
      characteristics and tested for interaction between period and SES. RESULTS: In
      both periods, high SES respondents (in all indicators) had lower current smoking
      levels and higher cessation ratios than those of middle or low SES. Inequalities
      in current smoking increased significantly in poorly educated adults of 45-64
      years of age (Odds Ratio (OR) low educational level compared with high: 2.00[1.79
      2.23] compared to pre-GFC 1.67[1.50-1.86], p for interaction = 0.02). Smoking
      cessation inequalities by income in 18-30 year olds increased with borderline
      significance during the GFC (OR low income compared to high income: 0.73[0.58
      0.91]) compared to pre-GFC (OR: 0.98[0.80-1.20]), p for interaction = 0.051).
      CONCLUSIONS: Overall, socioeconomic inequalities in current smoking and smoking
      cessation were unchanged during the GFC. However, current smoking inequalities by
      education, and smoking cessation inequalities by income, increased in specific
      age groups. Increased financial strain caused by the crisis may
      disproportionately affect smoking behaviour in some disadvantaged groups.

PMID- 25943386
TI  - qRT-PCR evaluation of the transcriptional response of zebra mussel to heavy
      metals.
AB  - BACKGROUND: The transcriptional response of adult zebra mussels (Dreissena
      polymorpha) to heavy metals (mercury, copper, and cadmium) was analyzed by
      quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) to study the
      coordinated regulation of different metal-, oxidative stress- and xenobiotic
      defence-related genes in gills and digestive gland. Regulatory network analyses
      allowed the comparison of this response between different species and taxa.
      RESULTS: Chemometric analyses allowed identifying the effects of these metals
      clearly separating control and treated samples of both tissues. Interactions
      between the different genes, either in the same or between both tissues, were
      analysed to identify correlations and to propose stress-related genes' regulatory
      networks. These networks were finally compared with existing data from human,
      mouse, zebrafish, Drosophila and the roundworm to evaluate their mechanistically
      known response to metals (and to stressors in general) with the correlations
      observed in the still poorly-known, invasive zebra mussel. CONCLUSIONS: Our
      analyses found a general conservation of regulation genes and of their
      interactions among the different considered species, and may serve as a guide to
      extrapolate regulatory data from model species to lesser-known environmentally
      (or medically) relevant species.

PMID- 25943387
TI  - Cross-species chimeras reveal BamA POTRA and beta-barrel domains must be fine
      tuned for efficient OMP insertion.
AB  - BAM is a conserved molecular machine, the central component of which is BamA.
      Orthologues of BamA are found in all Gram-negative bacteria, chloroplasts and
      mitochondria where it is required for the folding and insertion of beta-barrel
      containing integral outer membrane proteins (OMPs) into the outer membrane. BamA
      binds unfolded beta-barrel precursors via the five polypeptide transport
      associated (POTRA) domains at its N-terminus. The C-terminus of BamA folds into a
      beta-barrel domain, which tethers BamA to the outer membrane and is involved in
      OMP insertion. BamA orthologues are found in all Gram-negative bacteria and
      appear to function in a species-specific manner. Here we investigate the nature
      of this species-specificity by examining whether chimeric Escherichia coli BamA
      fusion proteins, carrying either the beta-barrel or POTRA domains from various
      BamA orthologues, can functionally replace E. coli BamA. We demonstrate that the
      beta-barrel domains of many BamA orthologues are functionally interchangeable. We
      show that defects in the orthologous POTRA domains can be rescued by compensatory
      mutations within the beta-barrel. These data reveal that the POTRA and barrel
      domains must be precisely aligned to ensure efficient OMP insertion. 

PMID- 25943388
TI  - Dynamic prediction of outcome for patients with severe aortic stenosis:
      application of joint models for longitudinal and time-to-event data.
AB  - BACKGROUND: Physicians utilize different types of information to predict patient
      prognosis. For example: confronted with a new patient suffering from severe
      aortic stenosis (AS), the cardiologist considers not only the severity of the AS
      but also patient characteristics, medical history, and markers such as BNP.
      Intuitively, doctors adjust their prediction of prognosis over time, with the
      change in clinical status, aortic valve area and BNP at each outpatient clinic
      visit. With the help of novel statistical approaches to model outcomes, it is now
      possible to construct dynamic event prediction models, employing longitudinal
      data such as AVA and BNP, and mimicking the dynamic adjustment of prognosis as
      employed intuitively by cardiologists. We illustrate dynamic prediction of
      patient survival and freedom from intervention, using baseline patient
      characteristics and longitudinal BNP data that are becoming available over time,
      from a cohort of patients with severe aortic stenosis. METHODS: A 3-step approach
      was employed: (1) construction of a mixed-effects model to describe temporal BNP
      progression, (2) jointly modeling the mixed-effects model with time-to-event data
      (death and freedom from intervention), and (3) using the joint model to build
      subject-specific prediction risk models. The dataset used for this purpose
      includes 191 patients with severe aortic stenosis who were followed over a 3-year
      time period. RESULTS: In the mixed-effects model BNP was significantly influenced
      by time, baseline patient age, gender, LV fractional ejection fraction and
      creatinine. Additionally, the joint model showed that an increasing BNP trend
      over time was found to be a significant predictor of death. CONCLUSIONS: By
      jointly modeling longitudinal data with time-to-event outcomes it is possible to
      construct individualized dynamic event prediction models that renew over time
      with accumulating evidence. It provides a potentially valuable evidence-based
      tool for everyday use in medical practice.

PMID- 25943389
TI  - Lesson to be learned from the renal denervation trials.

PMID- 25943390
TI  - Transverse colon cancer occurring at a colostomy site 35 years after colostomy: a
      case report.
AB  - BACKGROUND: Carcinomas occurring at colostomy sites are rare, and most of these
      are metachronous colorectal cancers. The median time between colostomy and
      development of a carcinoma at a colostomy site is 22 years, which exceeds the
      length of the recommended follow-up period. We report a rare case of a carcinoma
      of the transverse colon occurring at a colostomy site in a patient without a
      history of colorectal cancer. CASE REPORT: An 89-year-old woman presented with a
      tumor occurring at a colostomy site. Thirty-five years previously, she had
      undergone a transverse loop colostomy for an iatrogenic colon perforation that
      occurred during left ureteral lithotomy. Upon physical examination, the patient
      had a hard nodule measuring 3 cm at the colostomy site. A biopsy of the nodule
      suggested adenocarcinoma, and the preoperative diagnosis was transverse colon
      cancer. A laparotomy was performed via a peristomal incision with 5-mm skin
      margins, and the tumor was covered by a surgical glove to avoid any tumor
      seeding. The colon was separated from the tumor by 5-cm margins, and the specimen
      was removed en bloc. An end colostomy was constructed to a new site on the right
      side of the abdomen. The deficit in the abdominal wall was repaired, and the skin
      was closed via a purse-string suture. The final diagnosis of the stoma tumor was
      transverse colon cancer (T2, N0, M0, stage I). One year and five months after
      surgery, there was no evidence of recurrence. CONCLUSIONS: The occurrence of
      carcinomas at colostomy sites in patients without a history of colorectal cancer
      is rare. It is important to train ostomates to monitor the stoma for possible
      tumor recurrence.

PMID- 25943392
TI  - IL6 induces TAM resistance via kinase-specific phosphorylation of ERalpha in OVCA
      cells.
AB  - About 40-60% of ovarian cancer (OVCA) cases express ERalpha, but only a small
      proportion of patients respond clinically to anti-estrogen treatment with
      estrogen receptor (ER) antagonist tamoxifen (TAM). The mechanism of TAM
      resistance in the course of OVCA progression remains unclear. However, IL6 plays
      a critical role in the development and progression of OVCA. Our recent results
      indicated that IL6 secreted by OVCA cells may promote the resistance of these
      cells to TAM via ER isoforms and steroid hormone receptor coactivator-1. Here we
      demonstrate that both exogenous (a relatively short period of treatment with
      recombinant IL6) and endogenous IL6 (generated as a result of transfection with a
      plasmid encoding sense IL6) increases expression of pERalpha-Ser118 and pERalpha
      Ser167 in non-IL6-expressing A2780 cells, while deleting endogenous IL6
      expression in IL6-overexpressing CAOV-3 cells (by transfection with a plasmid
      encoding antisense IL6) reduces expression of pERalpha-Ser118 and pERalpha
      Ser167, indicating that IL6-induced TAM resistance may also be associated with
      increased expression of pERalpha-Ser118 and pERalpha-Ser167 in OVCA cells.
      Results of further investigation indicate that IL6 phosphorylates ERalpha at
      Ser118 and Ser167 by triggering activation of MEK/ERK and phosphotidylinositol 3
      kinase/Akt signaling, respectively, to activate the ER pathway and thereby induce
      OVCA cells resistance to TAM. These results indicate that IL6 secreted by OVCA
      cells may also contribute to the refractoriness of these cells to TAM via the
      crosstalk between ER and IL6-mediated intracellular signal transduction cascades.
      Overexpression of IL6 not only plays an important role in OVCA progression but
      also promotes TAM resistance. Our results indicate that TAM-IL6-targeted
      adjunctive therapy may lead to a more effective intervention than TAM alone. 

PMID- 25943394
TI  - Blood pressure measurement at two years in offspring of women randomized to a
      trial of metformin for GDM: follow up data from the MiG trial.
AB  - BACKGROUND: Offspring born following maternal gestational diabetes are at risk of
      excessive childhood weight gain and Type 2 diabetes in childhood, which in turn
      is associated with an increased rate of hypertension. We aimed to determine the
      systolic and diastolic blood pressure at two years of age in a cohort of children
      exposed to gestational diabetes mellitus using data from the MiG trial of
      metformin use in gestational diabetes. The secondary aim was to analyze these
      data by randomization of treatment to insulin or metformin. METHODS: The
      offspring of women who had gestational diabetes and had been assigned to either
      open treatment with metformin (with supplemental insulin if required) or insulin
      in the MiG trial were followed up at 2 years of age. Oscillometric measurement of
      BP in the right arm was performed by a researcher using an appropriately sized
      cuff. RESULTS: A total of 489 measurement blood pressure measurements were
      obtained in 170 of the 222 children who were seen at a median (range) age of 29
      (22-38) months corrected gestational age. At the time of assessment the mean (SD)
      weight and height was 13.8(2) kg and 90 (4.2) cm respectively. For the whole
      group the mean (SD) systolic pressure was 90.9 (9.9) mmHg and mean (SD) diastolic
      pressure was 55.7 (8.1) mmHg. No difference was found between the metformin and
      insulin treatment arms. In a regression model, height and weight were only two
      factors associated with the levels of systolic blood pressure. For each
      additional kg the systolic blood pressure increased by 1.0 mmHg. For each
      additional cm of height the systolic blood pressure increased by 0.42 mmHg.
      CONCLUSIONS: Blood pressure data was obtained at approximately two years of age
      in a substantial cohort of children whose mothers received treatment for GDM.
      These novel data compare favorably with published norms. CLINICAL TRIALS
      REGISTRY: This study was registered under the Australian New Zealand Clinical
      Trials Registry ( ACTRN12605000311651 ).

PMID- 25943391
TI  - Ubiquitylation of nuclear receptors: new linkages and therapeutic implications.
AB  - The nuclear receptor (NR) superfamily is a group of transcriptional regulators
      that control multiple aspects of both physiology and pathology and are broadly
      recognized as viable therapeutic targets. While receptor-modulating drugs have
      been successful in many cases, the discovery of new drug targets is still an
      active area of research, because resistance to NR-targeting therapies remains a
      significant clinical challenge. Many successful targeted therapies have harnessed
      the control of receptor activity by targeting events within the NR signaling
      pathway. In this review, we explore the role of NR ubiquitylation and discuss how
      the expanding roles of ubiquitin could be leveraged to identify additional entry
      points to control receptor function for future therapeutic development. 

PMID- 25943393
TI  - Evidence That the Origin of Naked Kernels During Maize Domestication Was Caused
      by a Single Amino Acid Substitution in tga1.
AB  - teosinte glume architecture1 (tga1), a member of the SBP-box gene family of
      transcriptional regulators, has been identified as the gene conferring naked
      kernels in maize vs. encased kernels in its wild progenitor, teosinte. However,
      the identity of the causative polymorphism within tga1 that produces these
      different phenotypes has remained unknown. Using nucleotide diversity data, we
      show that there is a single fixed nucleotide difference between maize and
      teosinte in tga1, and this difference confers a Lys (teosinte allele) to Asn
      (maize allele) substitution. This substitution transforms TGA1 into a
      transcriptional repressor. While both alleles of TGA1 can bind a GTAC motif,
      maize-TGA1 forms more stable dimers than teosinte-TGA1. Since it is the only
      fixed difference between maize and teosinte, this alteration in protein function
      likely underlies the differences in maize and teosinte glume architecture. We
      previously reported a difference in TGA1 protein abundance between maize and
      teosinte based on relative signal intensity of a Western blot. Here, we show that
      this signal difference is not due to tga1 but to a second gene, neighbor of tga1
      (not1). Not1 encodes a protein that has 92% amino acid similarity to TGA1 and
      that is recognized by the TGA1 antibody. Genetic mapping and phenotypic data show
      that tga1, without a contribution from not1, controls the difference in covered
      vs. naked kernels. No trait differences could be associated with the maize vs.
      teosinte alleles of not1. Our results document how morphological evolution can be
      driven by a simple nucleotide change that alters protein function.

PMID- 25943395
TI  - Cardiovascular surgery nurses' level of knowledge regarding delirium.
AB  - BACKGROUND: Studies have shown that nurses have a crucial role in the recognition
      of delirium; however, they have insufficient knowledge regarding the issue.
      OBJECTIVE: The aim of the study is to determine the knowledge level of
      cardiovascular surgery nurses regarding delirium. METHODS: A survey design was
      used. The population of the study consisted of 124 nurses employed at the
      cardiovascular surgery wards and intensive care units of universities as well as
      state and private hospitals located in two different cities in Turkey between May
      and June 2014. The sample consisted of 97 nurses employed at the aforementioned
      institutions and time. Data were collected using the questionnaire form depicting
      the demographic characteristics of the nurses and the knowledge form including
      the level of nurses' knowledge regarding delirium. For the evaluation of data,
      number, percentage, Kruskal-Wallis, Mann-Whitney U- and independent-samples t
      test were used. RESULTS: Nurses were between 18 and 47 years of age with a mean
      29.8 (SD = 6.80, the youngest = 18 and the oldest = 47) years. They spent a
      minimum of 1, a maximum of 25 and a median value of 3 (interquartile range, IQR:
      5) years working in cardiovascular surgery. As for the scores received from the
      knowledge form regarding delirium, the lowest was zero, the highest was 60, and
      the average score was 41.18 +/- 12.50 (a moderate level of knowledge). It was
      found that the nurses working in intensive care units, those who were chief
      nurses and those who received in-service training scored higher than the others.
      CONCLUSIONS: Cardiovascular surgery nurses had a moderate level of knowledge
      regarding delirium. This may result in the neglect of delirium or a misdiagnosis.
      RELEVANCE TO CLINICAL PRACTICE: It is recommended that training is provided that
      includes recognition, assessment and application of appropriate interventions to
      minimise the incidence of delirium.

PMID- 25943396
TI  - Safety of alternate day fasting and effect on disordered eating behaviors.
AB  - BACKGROUND: Alternate day fasting (ADF; ad libitum intake "feed day" alternated
      with 75% restriction "fast day"), is effective for weight loss, but the safety of
      the diet has been questioned. Accordingly, this study examined occurrences of
      adverse events and eating disorder symptoms during ADF. FINDINGS: Obese subjects
      (n = 59) participated in an 8-week ADF protocol where food was provided on the
      fast day. Body weight decreased (P < 0.0001) by 4.2 +/- 0.3%. Some subjects
      reported constipation (17%), water retention (2%), dizziness (<20%), and general
      weakness (<15%). Bad breath doubled from baseline (14%) to post-treatment (29%),
      though not significantly. Depression and binge eating decreased (P < 0.01) with
      ADF. Purgative behavior and fear of fatness remained unchanged. ADF helped
      subjects increase (P < 0.01) restrictive eating and improve (P < 0.01) body image
      perception. CONCLUSIONS: Therefore, ADF produces minimal adverse outcomes, and
      has either benign or beneficial effects on eating disorder symptoms.

PMID- 25943397
TI  - Neuroimmune and neuroendocrine abnormalities in depression: two sides of the same
      coin.
AB  - Major depressive disorder has been linked to alterations in several interacting
      systems, particularly with respect to neuroendocrine and neuroinflammatory
      dysfunction. Increased levels of both cortisol and proinflammatory cytokines have
      regularly been described. This presents an apparent paradox, given the well-known
      anti-inflammatory properties of glucocorticoids, including inhibition of cytokine
      release. There are two competing theories to resolve this paradox: one proposes
      that reduced glucocorticoid signaling, as a result of glucocorticoid resistance,
      creates a permissive environment for an overactive innate immune system; the
      other theory focuses on evidence that glucocorticoids can be proinflammatory
      under some circumstances, depending on context and temporal factors. This review
      assesses the evidence base and limitations of both theories, discussing animal
      and clinical data, and preliminary work in human neural cells. Further work to
      delineate the relationship between neuroimmune and neuroendocrine systems in
      depression will be critical for understanding the biological perturbations
      underpinning depression, and therefore, for discerning treatment targets, and we
      include suggestions for future directions. 

PMID- 25943398
TI  - Effectiveness of peer support for improving glycaemic control in patients with
      type 2 diabetes: a meta-analysis of randomized controlled trials.
AB  - BACKGROUND: To assess the effects of peer support at improving glycemic control
      in patients with type 2 diabetes. METHODS: Relevant electronic databases were
      sought for this investigation up to Dec 2014. Randomized controlled trials
      involving patients with type 2 diabetes that evaluated the effect of peer support
      on glycated hemoglobin (HbA1c) concentrations were included. The pooled mean
      differences (MD) between intervention and control groups with 95% confidence
      interval (CI) were calculated using random-effects model. The Cochrane
      Collaboration's tool was used to assess the risk of bias. RESULTS: Thirteen
      randomized controlled trials met the inclusion criteria. Peer support resulted in
      a significant reduction in HbA1c (MD -0.57 [95% CI: -0.78 to -0.36]). Programs
      with moderate or high frequency of contact showed a significant reduction in
      HbA1c levels (MD -0.52 [95% CI: -0.60 to -0.44] and -0.75 [95% CI: -1.21 to 
      0.29], respectively), whereas programs with low frequency of contact showed no
      significant reduction (MD -0.32 [95% CI: -0.74 to 0.09]). The reduction in HbA1c
      were greater among patients with a baseline HbA1c >= 8.5% (MD -0.78 [95% CI: 
      1.06 to -0.51]) and between 7.5 ~ 8.5% (MD -0.76 [95% CI: -1.05 to -0.47]), than
      patients with HbA1c < 7.5% (MD -0.08 [95% CI: -0.32 to 0.16]). CONCLUSIONS: Peer
      support had a significant impact on HbA1c levels among patients with type 2
      diabetes. Priority should be given to programs with moderate or high frequency of
      contact for target patients with poor glycemic control rather than programs with
      low frequency of contact that target the overall population of patients.

PMID- 25943399
TI  - Midwives' perspectives of their ability to promote the oral health of pregnant
      women in Victoria, Australia.
AB  - BACKGROUND: Midwives have a potential role in promoting the oral health of
      pregnant women although they have little formal training in this area. The aim of
      this study was to explore the perspectives of midwives in Victoria towards
      incorporating oral health promotion into their antenatal practice after
      undergoing training through the Midwifery Initiated Oral Health (MIOH) online
      education program. METHODS: A purposive sample of thirty-nine midwives from
      maternity services across Victoria, Australia were invited to participate in an
      online MIOH education program in October 2012. The program included three self
      paced modules covering oral health screening, referral processes, and theoretical
      and practical skill assessments. A mixed methods design was used to capture
      midwives perspectives. Evaluation questionnaires, completed pre- and post
      training, captured knowledge and confidence (confidence likert scale), and also
      included five opened-ended questions post-training. Open-ended questions,
      feedback forms and unsolicited emails formed the data for qualitative analysis.
      Data were analysed using content and thematic analysis and descriptive
      statistics. RESULTS: Thirty-three midwives completed the MIOH education program
      and demonstrated a significant increase (51.5%) in their confidence to promote
      oral health. All participants viewed the program as suitable, acceptable and
      useful for their practice and were happy to recommend the course to other
      Victorian midwives. Participants indicated that it would be feasible to
      incorporate oral health into the first antenatal booking visit and recognised
      that oral health promotion was within their scope of practice. CONCLUSIONS: This
      study has shown that the MIOH education program is a valued resource that can
      assist midwives to increase their confidence and skills to incorporate oral
      health promotion into their practice. A key barrier identified was time
      constraints during antenatal care booking visits. However, it is evident that
      with relevant training it would be feasible and acceptable for Victorian midwives
      to incorporate oral health promotion within their practice. The current
      engagement with midwives in Victoria and other parts of Australia provides an
      opportunity to continue to explore and define the role of antenatal health care
      professionals in oral health promotion at a state and national level.

PMID- 25943400
TI  - Development of nanosized silver-substituted apatite for biomedical applications:
      A review.
AB  - The favorable biocompatibility of hydroxyapatite (HA) makes it a popular bone
      graft material as well as a coating layer on metallic implant. To reduce implant
      related infections, silver ions were either incorporated into the apatite during
      co-precipitation process (AgHA-CP) or underwent ion-exchange with the calcium
      ions in the apatite (AgHA-IE). However, the distribution of silver ions in AgHA
      CP and AgHA-IE was different, thus affecting the antibacterial action. Several
      studies reported that nanosized AgHA-CP containing 0.5 wt.% of silver provided an
      optimal trade-off between antibacterial properties and cytotoxicity.
      Nevertheless, nanosized AgHA and AgHA nanocoatings could not function ideally due
      to the compromise in the bone differentiation of mesenchymal stem cells, as
      evidenced in the reduced alkaline phosphatase, type I collagen and osteocalcin.
      Preliminary studies showed that biological responses of nanosized AgHA and AgHA
      nanocoatings could be improved with the addition of silicon. This review will
      discuss on nanosized AgHA and AgHA nanocoatings. FROM THE CLINICAL EDITOR: In
      many patients needing bone graft material, hydroxyapatite (HA) has proven to be a
      popular choice. Nonetheless, implant-related infections remain a major concern.
      Hence, effective preventive measures are needed. In this review article, the
      authors discussed the application of incorporating silver nanoparticles in HA and
      its use as bone graft biomaterials together with the addition of silica.

PMID- 25943401
TI  - Desmoid tumor of the pancreas: a case report.
AB  - INTRODUCTION: Desmoid tumor is a rare, benign, usually asymptomatic fibromatous
      lesion. The etiology is unknown and the diagnosis is based on histopathological
      examination. The treatment is complete resection of the tumor. Pancreatic desmoid
      tumor is extremely rare. In the literature there have been only 11 cases
      described, most of them as solid or solid-cystic masses. We report the case of a
      patient with an isolated cystic pancreatic desmoid tumor that is, to the best of
      our knowledge, the second reported case. CASE PRESENTATION: A 13-year old
      Caucasian boy presented with recurrent pain of two months' duration in the left
      hypochondrium of his abdomen. An ultrasound examination and computed tomography
      scan revealed the presence of a cystic mass located in his splenic hilum, tightly
      adjacent to the pancreatic tail. A splenic cyst was suspected. Operative findings
      showed a 10 x 10 cm cystic mass tightly connected to the pancreatic tail and left
      colonic flexure, adherent to the spleen, splenic vein and artery. Distal
      splenopancreatectomy with en bloc resection of the left colonic flexure was
      performed. Histological analysis confirmed that the resection was complete. The
      mass had infiltrated the pancreatic parenchyma. All tumor cells were positive for
      anti-beta-catenin staining characteristic for desmoid tumor. No abnormalities in
      the spleen and colon were found. CONCLUSIONS: Isolated sporadic pancreatic
      desmoid tumor with cyst formation is extremely rare and its diagnosis can be
      difficult, especially because of uncharacteristic symptoms and radiological
      findings, as in our patient. This case report should be of interest not only to
      surgeons, as the treatment of choice is radical resection, but also
      gastroenterologists, considering it is in close relation with familial
      adenomatous polyposis, and oncologists as the reason for differentiation with
      other pancreatic tumors.

PMID- 25943402
TI  - Steps towards establishing a new medical college in the Kingdom of Saudi Arabia:
      an insight into medical education in the Kingdom.
AB  - BACKGROUND: The percentage of Saudi physicians practicing in the public health
      sector did not exceed 22.6% in 2009, and did not reach 20% in 2006. This is
      despite the fact that more than 80% of the Saudi population seeks health care in
      the public health sector. Such a low percentage of Saudi physicians is even
      significantly lower in the private health sector. With a fast growing population,
      and a low percentage of Saudi nationals practicing medicine, the need to
      establish new medical colleges in the Kingdom became a must. This study reflects
      on the steps followed in establishing the College of Medicine at Al-Imam Mohammad
      Ibn Saud Islamic University, and provides a comprehensive insight into medical
      education in the Kingdom. METHODS: A sub-committee derived from the Saudi Medical
      Colleges Deans' Committee was created and chaired by the founding dean of Al-Imam
      College of Medicine. The main goals of the sub-committee were to analyze the
      status of medical education in the Kingdom, and to produce an action plan to be
      followed when establishing a new medical college in the country. RESULTS: The sub
      committee produced a working document, which included recommendations and action
      plan. A medical college yet to be established should take into consideration
      right from the beginning both institutional and program accreditation. To achieve
      this goal, there are five main pillars to be planned by six main task forces.
      Embedded among these pillars are twenty-one domains. The analysis of the status
      of medical education in the Kingdom revealed some interesting observations, which
      are discussed in details in the manuscript. CONCLUSIONS: Establishing a new
      medical college should not be about just increasing the number of medical
      colleges as a response to the shortage of doctors. It is a lengthy "surgical
      operation" that requires careful and timely planning in order to anticipate and
      prevent any damage, and to ensure optimal outcomes. In this regard, a detailed
      analysis of what already exists and what needs to be done is crucial.

PMID- 25943403
TI  - Primary intestinal lymphangiectasia treated with rapamycin in a child with
      tuberous sclerosis complex (TSC).
AB  - Primary intestinal lymphangiectasia (PIL) is a rare protein-losing enteropathy
      characterized by a congenital malformation of the lymphatic vessels of the small
      intestine causing insufficient drainage and leakage of lymph fluid. Tuberous
      sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized
      by benign hamartomas in multiple organ systems. While the lymphatic system has
      been implicated in TSC through lymphangioleiomyomatosis (LAM) and lymphedema,
      this paper reports the first case of PIL in TSC, a female patient with a TSC2
      mutation. She developed persistent and significant abdominal distension with
      chronic diarrhea during her first year of life. Due to lack of treatment options
      and the involvement of the mTOR pathway in TSC, a trial of an mTOR inhibitor,
      rapamycin, was initiated. This treatment was highly effective, with improvement
      in clinical symptoms of PIL as well as abnormal laboratory values including VEGF
      C, which was elevated to over seven times the normal upper limit before
      treatment. This case suggests that PIL is a rare manifestation of TSC, warranting
      the use of mTOR inhibitors in future studies.

PMID- 25943404
TI  - Quantitative and multiplexed DNA methylation analysis using long-read single
      molecule real-time bisulfite sequencing (SMRT-BS).
AB  - BACKGROUND: DNA methylation has essential roles in transcriptional regulation,
      imprinting, X chromosome inactivation and other cellular processes, and aberrant
      CpG methylation is directly involved in the pathogenesis of human imprinting
      disorders and many cancers. To address the need for a quantitative and highly
      multiplexed bisulfite sequencing method with long read lengths for targeted CpG
      methylation analysis, we developed single-molecule real-time bisulfite sequencing
      (SMRT-BS). RESULTS: Optimized bisulfite conversion and PCR conditions enabled the
      amplification of DNA fragments up to ~1.5 kb, and subjecting overlapping 625-1491
      bp amplicons to SMRT-BS indicated high reproducibility across all amplicon
      lengths (r=0.972) and low standard deviations (<=0.10) between individual CpG
      sites sequenced in triplicate. Higher variability in CpG methylation quantitation
      was correlated with reduced sequencing depth, particularly for intermediately
      methylated regions. SMRT-BS was validated by orthogonal bisulfite-based
      microarray (r=0.906; 42 CpG sites) and second generation sequencing (r=0.933; 174
      CpG sites); however, longer SMRT-BS amplicons (>1.0 kb) had reduced, but very
      acceptable, correlation with both orthogonal methods (r=0.836-0.897 and r=0.892
      0.927, respectively) compared to amplicons less than ~1.0 kb (r=0.940-0.951 and
      r=0.948-0.963, respectively). Multiplexing utility was assessed by simultaneously
      subjecting four distinct CpG island amplicons (702-866 bp; 325 CpGs) and 30
      hematological malignancy cell lines to SMRT-BS (average depth of 110X), which
      identified a spectrum of highly quantitative methylation levels across all
      interrogated CpG sites and cell lines. CONCLUSIONS: SMRT-BS is a novel, accurate
      and cost-effective targeted CpG methylation method that is amenable to a high
      degree of multiplexing with minimal clonal PCR artifacts. Increased sequencing
      depth is necessary when interrogating longer amplicons (>1.0 kb) and the
      previously reported bisulfite sequencing PCR bias towards unmethylated DNA should
      be considered when measuring intermediately methylated regions. Coupled with an
      optimized bisulfite PCR protocol, SMRT-BS is capable of interrogating ~1.5 kb
      amplicons, which theoretically can cover ~91% of CpG islands in the human genome.

PMID- 25943405
TI  - Case of a lung mass due to melioidosis in Mexico.
AB  - BACKGROUND: Melioidosis, an infection caused by the gram-negative bacterium
      Burkholderia pseudomallei, is an important cause of pneumonia, skin infection,
      sepsis, and death in Southeast Asia and Australia, but is exceedingly rare in
      North America. Pulmonary melioidosis typically presents as acute bacterial
      pneumonia or cavitary lung lesions resembling tuberculosis. CASE REPORT: We
      report melioidosis in a 70-year-old active smoker from Mexico with no history of
      travel to disease-endemic areas. The patient presented with a left
      supraclavicular abscess and a non-cavitary, left lung mass encasing a pulmonary
      vein. Incision and drainage of the patient's subcutaneous abscess isolated B.
      pseudomallei, and fine-needle aspiration of enlarged mediastinal lymph nodes
      revealed the presence of intracellular gram-negative bacilli with no evidence of
      malignancy. Biochemical tests determined that the strain the patient acquired
      from Mexico is identical to only 1 other isolate from Thailand. CONCLUSIONS: This
      report highlights the blurring epidemiological borders of this organism, its rare
      presentation mimicking lung malignancy, and an aggressive antimicrobial treatment
      that resulted in resolution of the patient's symptoms.

PMID- 25943406
TI  - Highly reliable top-gated thin-film transistor memory with semiconducting,
      tunneling, charge-trapping, and blocking layers all of flexible polymers.
AB  - The core components of a floating-gate organic thin-film transistor nonvolatile
      memory (OTFT-NVM) include the semiconducting channel layer, tunneling layer,
      floating-gate layer, and blocking layer, besides three terminal electrodes. In
      this study, we demonstrated OTFT-NVMs with all four constituent layers made of
      polymers based on consecutive spin-coating. Ambipolar charges injected and
      trapped in a polymer electret charge-controlling layer upon gate program and
      erase field successfully allowed for reliable bistable channel current levels at
      zero gate voltage. We have observed that the memory performance, in particular
      the reliability of a device, significantly depends upon the thickness of both
      blocking and tunneling layers, and with an optimized layer thickness and
      materials selection, our device exhibits a memory window of 15.4 V, on/off
      current ratio of 2 * 10(4), read and write endurance cycles over 100, and time
      dependent data retention of 10(8) s, even when fabricated on a mechanically
      flexible plastic substrate. 

PMID- 25943407
TI  - Freely chosen stride frequencies during walking and running are not correlated
      with freely chosen pedalling frequency and are insensitive to strength training.
AB  - Despite biomechanical differences between walking, running, and cycling, these
      types of movement are supposedly generated by shared neural networks. According
      to this hypothesis, we investigated relationships between movement frequencies in
      these tasks as well as effects of strength training on locomotion behaviour. The
      movement frequencies during walking, running, and cycling were 58.1+/-2.6 strides
      min(-1), 81.3+/-4.4 strides min(-1), and 77.2+/-11.5 revolutions min(-1),
      respectively (n=27). Stride frequencies in walking and running correlated
      positively (r=0.72, p<0.001) while no significant correlations were found between
      stride frequencies during walking and running, respectively, and pedalling
      frequency (r=0.16, p=0.219 and r=0.04, p=0.424). Potential changes in the freely
      chosen stride frequencies and stride phase characteristics were also investigated
      during walking and running through 4 weeks of (i) hip extension strength training
      (n=9), (ii) hip flexion strength training (n=9), and (iii) no intervention (n=9).
      Results showed that stride characteristics were unaffected by strength training.
      That is in contrast to previous observations of decreased pedalling frequency
      following strength training. In total, these results are proposed to indicate
      that walking and running movements are robustly generated due to an evolutionary
      consolidation of the interaction between the musculoskeletal system and neural
      networks. Further, based on the present results, and the fact that cycling is a
      postnatally developed task that likely results in a different pattern of
      descending and afferent input to rhythm generating neural networks than walking
      and running, we propose pedalling to be generated by neural networks mainly
      consolidated for locomotion.

PMID- 25943408
TI  - Gait characteristics and sensory abilities of older adults are modulated by
      gender.
AB  - Despite the general perception that women and men walk differently, little is
      known about the reasons for these differences, especially in older adults.
      Previous work on gender differences in older adults has focused on spatiotemporal
      parameters. This study aims to assess gender-related differences in gait
      spatiotemporal and quality parameters when walking on a flat walkway at two
      different self-selected speeds: comfortable and fast. Sensorimotor abilities
      (Strength, agility, standing balance, reaction time) were also compared by
      gender, and gender-specific associations between spatiotemporal and sensorimotor
      parameters and gait quality were studied. Two tri-axial accelerometers were used
      at head and pelvis levels to investigate spatiotemporal parameters (step length,
      velocity and cadence), and gait quality (harmonic ratios (HR) and attenuation of
      accelerations between body levels) in 122 older adults (90 women, 69.7+/-5.1 y.o.
      and 32 men, 71.6+/-6.4 y.o.). Both men and women walked with similar speed;
      however women presented faster cadence and shorter steps than men at both walking
      speeds. Women also walked with greater vertical HR (head and pelvis),
      mediolateral pelvis HR, and attenuation (mediolateral and anteroposterior) than
      men. Women had better control of standing balance on foam (eyes open and closed)
      and tandem test. Moreover, balance on foam, tandem test, step length and cadence
      were associated to gender-specific gait quality parameters. The aging process
      seems to be affecting men and women differently, thus, gender differences should
      be considered when preparing intervention programs to improve balance and gait in
      older populations or when establishing normative data for balance and gait in
      older adults.

PMID- 25943409
TI  - [Double-balloon device and intravaginal dinoprostone for cervical ripening in
      women with unfavourable cervix].
AB  - OBJECTIVES: To compare the efficiency of a double cervical ripening (mechanical
      agent and dinoprostone) to a dinoprostone-only ripening in women with an
      unfavourable cervix. METHODS: In a retrospective study from January 2008 to
      October 2013, 96 patients were included with the following criteria: pregnancies
      over 37 weeks, singleton, vertex presentation, medical indication for induction
      of labor, no premature rupture of membranes and very unfavourable cervix (Bishop
      score <= 3). Patients were classified into 2 groups: intravaginal dinoprostone
      for 24h (prostaglandin group, n=38) and double-balloon device for 12h followed by
      intravaginal dinoprostone for 24h (balloon+prostaglandin group, n=58). RESULTS:
      There was no difference in vaginal delivery rates between the 2 groups
      (balloon+prostaglandin group 51.7%, prostaglandin group 50%, P=0.87). The Bishop
      score after cervical ripening was significantly higher in the
      balloon+prostaglandin group (4.4 versus 2.4, P<0.0001), but the interval between
      the induction and the delivery was longer (33.6h versus 24.9h, P=0.0044). There
      was no significant difference for maternal and neonatal complications.
      CONCLUSION: A double cervical ripening (with mechanical agent and dinoprostone)
      allows the Bishop score to be improved without increasing the rate of vaginal
      delivery, for patients with a Bishop score <= 3.

PMID- 25943410
TI  - Anaesthesia and the patient with diabetes.
AB  - AIMS: To provide updated knowledge regarding the airway management and the
      possibility of difficult intubation in diabetic patients. MATERIALS AND METHODS:
      We preformed a systematic literature review of the English language literature,
      published over the past 10 years which deals with this subject. RESULTS: The vast
      majority of the modern literature data supports the fact that diabetic population
      has higher risk for difficult intubation occurrence. The most important
      characteristics of diabetic patients that are considered to be contributing
      factors for the difficult intubation are obesity, increased neck circumference
      and stiff joint syndrome. CONCLUSION: A special attention and thorough
      preoperative preparation should be given to patients with diabetes. In order to
      predict and prevent difficult intubation in these patients, further studies are
      needed to investigate this issue closely.

PMID- 25943411
TI  - Levels of triglycerides, cholesterol, LDL, HDL and glucose in patients with
      schizophrenia, unipolar depression and bipolar disorder.
AB  - AIMS: The aim of this study is to investigate differences in triglycerides (TGA),
      cholesterol (TC), HDL, LDL and glucose (FPG) levels in patients with acute
      schizophrenia, unipolar depression, bipolar depression and bipolar mania.
      RESULTS: Results for 2305 Caucasian patients were included in the study (1377
      women, 59.7%; mean age 45.6). Mean TGA level was: schizophrenia: 139.9+/-90.6
      mg/dL, unipolar depression: 125.4+/-70.8 mg/dL, bipolar disorder: 141.1+/-81.9
      mg/dL, bipolar depression: 147.7+/-82.8 mg/dL mg/dL, bipolar mania: 120.2+/-76.1
      mg/dL, inter-group differences were significant (p<0.001). Mean TC level was:
      schizophrenia: 188.5+/-40.4 mg/dL, unipolar depression: 198.8+/-50.7 mg/dL,
      bipolar disorder: 194.4+/-48.3 mg/dL, bipolar depression: 198.9+/-48.8 mg/dL,
      bipolar mania: 180.1+/-43.8 mg/dL, inter-group differences were significant
      (p<0.001). Mean HDL level was: schizophrenia: 45.3+/-13.9 mg/dL, unipolar
      depression: 48.1+/-14.8 mg/dL, bipolar disorder: 45.4+/-15.3 mg/dL, bipolar
      depression: 45.1+/-15.4 mg/dL, bipolar mania: 46.4+/-15.1 mg/dL, inter-group
      differences were significant (p<0.001). Mean LDL level was: schizophrenia:
      115.4+/-34.7 mg/dL, unipolar depression: 125.7+/-44.1 mg/dL, bipolar disorder:
      120.9+/-42.1 mg/dL, bipolar depression: 124.5+/-43.1 mg/dL, bipolar mania:
      109.3+/-36.9 mg/dL, inter-group differences were significant (p<0.001). Mean FPG
      level was: schizophrenia: 95.9+/-24.9 mg/dL, unipolar depression: 94.8+/-22.9
      mg/dL, bipolar disorder: 97.2+/-24.4 mg/dL, bipolar depression: 98.3+/-25.3
      mg/dL, bipolar mania: 93.9+/-21.1 mg/dL, inter-group differences were not
      significant (p=0.08). Odds ratios for glucose and lipids abnormalities,
      correlations with age, sex distribution in diagnostic groups for normal ranges of
      glucose and lipids, differences in glucose and lipids levels between the age
      groups were also calculated. CONCLUSIONS: Our results confirm that there is a
      high prevalence of lipid and glucose abnormalities in patients with schizophrenia
      and mood disorders (both unipolar and bipolar). However, we have demonstrated
      that these diagnostic groups differ in terms of types and frequency of these
      metabolic dysfunctions. Women and patients aged 40+ are at particularly high
      risk.

PMID- 25943412
TI  - The UK Pancreas Allocation Scheme for Whole Organ and Islet Transplantation.
AB  - In order to develop a national allocation scheme for donor pancreases, factors
      affecting waiting time and transplant outcomes in the United States (US) and
      United Kingdom (UK) were analyzed and compared. Blood group, sensitization,
      dialysis requirement, and whether the patient was waiting for a kidney and
      pancreas or pancreas alone affected waiting time in both countries; ethnicity and
      body mass index (BMI) also affected waiting time in the US. Ninety-day pancreas
      survival was similar in the UK and US, and was poorer for patients receiving a
      pancreas alone, with older donors, higher BMI and longer duration of ischemia in
      both countries. Factors affecting outcome, together with published data on
      factors affecting islet transplantation, informed the development of a points
      based allocation scheme for deceased donor pancreases in the UK providing
      equitable access for both whole organ and islet recipients through a single
      waiting list. Analysis of the allocation scheme 3 years after its introduction in
      December 2010 showed that the results were broadly as simulated, with a
      significant reduction in the number of long waiting patients and an increase in
      the number of islet transplants. There remains a surplus of highly sensitized
      patients in the waiting list, which the scheme should address in time. 

PMID- 25943413
TI  - Nurse staffing issues are just the tip of the iceberg: a qualitative study about
      nurses' perceptions of nurse staffing.
AB  - OBJECTIVE: To obtain in-depth insight into the perceptions of nurses in the
      Netherlands regarding current nurse staffing levels and use of nurse-to-patient
      ratios (NPR) and patient classification systems (PCS). BACKGROUND: In response to
      rising health care demands due to ageing of the patient population and increasing
      complexity of healthcare, hospital boards have been implementing NPRs and PCSs.
      However, many nurses at the unit level believe that staffing levels have become
      critically low, endangering the quality and safety of their patient care.
      METHODS: This descriptive phenomenological qualitative study was conducted in a
      1000-bed Dutch university hospital among 24 wards of four specialties (surgery,
      internal medicine, neurology, gynaecology & obstetrics and paediatric care). Data
      were collected from September until December 2012. To collect data four focus
      groups (n=44 nurses) were organized. Additionally, a total of 27 interviews (20
      head nurses, 4 nurse directors and 3 quality advisors) were conducted using
      purposive sampling. The focus groups and interviews were audiotaped, transcribed
      and subjected to thematic analysis. RESULTS: Nurse staffing issues appear to be
      merely the 'tip of the iceberg'. Below the surface three underlying main themes
      became clear - nursing behaviour, authority, and autonomy - which are linked by
      one overall theme: nurses' position. In general, nurses' behaviour, way of
      thinking, decision-making and communication of thoughts or information differs
      from other healthcare disciplines, e.g. physicians and quality advisors. This
      results in a perceived and actual lack of authority and autonomy. This in turn
      hinders them to plead for adequate nurse staffing in order to achieve the common
      goal of safe and high-quality patient care. Nurses desired a valid nursing care
      intensity system as an interdisciplinary and objective communication tool that
      makes nursing care visible and creates possibilities for better positioning of
      nurses in hospitals and further professionalization in terms of enhanced
      authority and autonomy. CONCLUSIONS: The perceived subservient position of nurses
      in the hospital appears to be the root cause of nurse staffing problems. It is
      yet unknown whether an objective PCS to measure nursing care intensity would help
      them communicate effectively and credibly, thereby improving their own position.

PMID- 25943414
TI  - A Tumor-Hosting Parasite!

PMID- 25943415
TI  - Martin F. Kagnoff, MD: 1941-2014.

PMID- 25943416
TI  - Erratum: Epithelial-specific A2B adenosine receptor signaling protects the
      colonic epithelial barrier during acute colitis.

PMID- 25943417
TI  - Inferring natural selection signals in Plasmodium vivax-encoded proteins having a
      potential role in merozoite invasion.
AB  - Detecting natural selection signals in Plasmodium parasites antigens might be
      used for identifying potential new vaccine candidates. Fifty-nine Plasmodium
      vivax-Sal-I genes encoding proteins having a potential role in invasion were used
      as query for identifying them in recent P. vivax strain genome sequences and two
      closely-related Plasmodium species. Several measures of DNA sequence variation
      were then calculated and selection signatures were detected by using different
      approaches. Our results may be used for determining which genes expressed during
      P. vivax merozoite stage could be prioritised for further population genetics or
      functional studies for designing a P. vivax vaccine which would avoid allele
      specific immune responses. 

PMID- 25943418
TI  - Merkel cell carcinoma of the lower leg with retroperitoneal GIST: a very rare
      association.
AB  - Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin. Although
      its association with other malignancies is well known, an association with
      gastrointestinal stromal tumor (GIST) has yet not been described.We report about
      a 65-year-old female patient who presented with a hypervascularized subcutaneous
      tumor mass of her left calf. Resection of the primary tumor and histopathological
      investigations confirmed the diagnosis of MCC. The patient was treated by delayed
      Mohs surgery, and tumor-free margins were obtained. Sentinel lymph node biopsy
      was negative for metastatic spread. Primary tumor and lymph node basin were
      treated by adjuvant radiotherapy. During staging of the patient, a second
      malignancy-a GIST-was detected. Neoadjuvant treatment with multikinase inhibitor
      imatinib induced a partial response of GIST that was eventually removed by
      surgery. However, 8 months later, the patient developed subcutaneous regional
      metastases of MCC, which were surgically removed. Adjuvant therapy was planned by
      oncologists.To the best of our knowledge, the occurrence of MCC and GIST in the
      same patient has yet not been reported. In contrast to GIST, MCC did not respond
      to imatinib, although c-kit mutations are common in MCC. 

PMID- 25943419
TI  - High proline-related inhibition of serum prolidase enzyme activity in
      scleroderma.

PMID- 25943420
TI  - Postprandial Dysmetabolism and Oxidative Stress in Type 2 Diabetes: Pathogenetic
      Mechanisms and Therapeutic Strategies.
AB  - Postprandial dysmetabolism in type 2 diabetes (T2D) is known to impact the
      progression and evolution of this complex disease process. However, the
      underlying pathogenetic mechanisms still require full elucidation to provide
      guidance for disease prevention and treatment. This review focuses on the marked
      redox changes and inflammatory stimuli provoked by the spike in blood glucose and
      lipids in T2D individuals after meals. All the causes of exacerbated postprandial
      oxidative stress in T2D were analyzed, also considering the consequence of
      enhanced inflammation on vascular damage. Based on this in-depth analysis,
      current strategies of prevention and pharmacologic management of T2D were
      critically reexamined with particular emphasis on their potential redox-related
      rationale. 

PMID- 25943421
TI  - Prescribing of long-acting beta-2-agonists/inhaled corticosteroids after the
      SMART trial.
AB  - BACKGROUND: After the SMART trial evaluating the safety of salmeterol (long
      acting beta-2-agonist (LABA)) in asthma patients, regulatory actions were taken
      to promote a guideline-adherent prescribing of LABA only to patients receiving
      inhaled corticosteroids (ICS). We aim to analyse LABA- and ICS-related
      prescription patterns after the SMART trial in Germany. METHODS: Patients
      documented in the Bavarian Association of Statutory Health Insurance Physicians
      database (approximately 10.5 million people) were included if they had a
      diagnosis of asthma and at least one prescription of LABA and/or ICS between 2004
      and 2008. Annual period prevalence rates (PPRs) were estimated and Cochrane
      Armitage tests were used for time trend analyses. RESULTS: Highest annual PPRs
      were found for budesonide and the fixed combination of salmeterol/fluticasone.
      The proportion of "concomitant LABA and ICS users" increased from 52.0 to 57.6%
      within the study period, whereas for "LABA users without ICS" a slight decrease
      from 6.5 to 5.4% was found. In 2008, the proportion of patients with at least one
      quarter with a LABA prescription without concomitant ICS was highest in elderly,
      male patients (~20%). In the majority of these patients, a concomitant diagnosis
      of COPD (i.e. asthma-COPD overlap syndrome [ACOS]) was present. CONCLUSIONS:
      Between 2004 and 2008, we found a moderate increase in guideline-adherent LABA
      prescribing in a representative German population. Elderly men received a
      significant number of LABA prescriptions without concomitant ICS probably due to
      ACOS.

PMID- 25943423
TI  - Capsaicin-sensitive C- and A-fibre nociceptors control long-term potentiation
      like pain amplification in humans.
AB  - Long-term potentiation in the spinal dorsal horn requires peptidergic C-fibre
      activation in animals. Perceptual correlates of long-term potentiation following
      high-frequency electrical stimulation in humans include increased sensitivity to
      electrical stimuli at the high frequency stimulation site (homotopic pain-long
      term potentiation) and increased sensitivity to pinprick surrounding the high
      frequency stimulation site (heterotopic pain-long-term potentiation, equivalent
      to secondary hyperalgaesia). To characterize the peripheral fibre populations
      involved in induction of pain-long-term potentiation, we performed two selective
      nerve block experiments in 30 healthy male volunteers. Functional blockade of
      TRPV1-positive nociceptors by high-concentration capsaicin (verified by loss of
      heat pain) significantly reduced pain ratings to high frequency stimulation by
      47% (P < 0.001), homotopic pain-long-term potentiation by 71% (P < 0.01),
      heterotopic pain-long-term potentiation by 92% (P < 0.001) and the area of
      secondary hyperalgesia by 76% (P < 0.001). The selective blockade of A-fibre
      conduction by nerve compression (verified by loss of first pain to pinprick)
      significantly reduced pain ratings to high frequency stimulation by 37% (P <
      0.01), but not homotopic pain-long-term potentiation (-5%). It had a marginal
      effect on heterotopic pain-long-term potentiation (-35%, P = 0.059), while the
      area of secondary hyperalgesia remained unchanged (-2%, P = 0.88). In conclusion,
      all nociceptor subclasses contribute to high frequency stimulation-induced pain
      (with a relative contribution of C > Adelta fibres, and an equal contribution of
      TRPV1-positive and TRPV1-negative fibres). TRPV1-positive C-fibres are the main
      inducers of both homotopic and heterotopic pain-long-term potentiation. TRPV1
      positive A-fibres contribute substantially to the induction of heterotopic pain
      long-term potentiation. TRPV1-negative C-fibres induce a component of homotopic
      self-facilitation but not heterotopic pain-long-term potentiation. TRPV1-negative
      A-fibres are the main afferents mediating pinprick pain and hyperalgesia,
      however, they do not appear to contribute to the induction of pain-long-term
      potentiation. These findings show that distinct peripheral fibre classes mediate
      induction of long-term potentiation-like pain amplification, its spatial spread
      to adjacent skin (i.e. secondary hyperalgesia), and the resulting enhanced
      sensitivity to pinprick in humans. Nociceptive afferents that induce pain
      amplification can be readily dissociated from those mediating pain. These
      findings add substantially to our understanding of the mechanisms of pain
      amplification, that form the basis for understanding the mechanisms of
      hyperalgesia encountered in patients.See Sandkuhler (doi:10.1093/brain/awv193)
      for a scientific commentary on this article. 

PMID- 25943422
TI  - Brain structure-function associations in multi-generational families genetically
      enriched for bipolar disorder.
AB  - Recent theories regarding the pathophysiology of bipolar disorder suggest
      contributions of both neurodevelopmental and neurodegenerative processes. While
      structural neuroimaging studies indicate disease-associated neuroanatomical
      alterations, the behavioural correlates of these alterations have not been well
      characterized. Here, we investigated multi-generational families genetically
      enriched for bipolar disorder to: (i) characterize neurobehavioural correlates of
      neuroanatomical measures implicated in the pathophysiology of bipolar disorder;
      (ii) identify brain-behaviour associations that differ between diagnostic groups;
      (iii) identify neurocognitive traits that show evidence of accelerated ageing
      specifically in subjects with bipolar disorder; and (iv) identify brain-behaviour
      correlations that differ across the age span. Structural neuroimages and multi
      dimensional assessments of temperament and neurocognition were acquired from 527
      (153 bipolar disorder and 374 non-bipolar disorder) adults aged 18-87 years in 26
      families with heavy genetic loading for bipolar disorder. We used linear
      regression models to identify significant brain-behaviour associations and test
      whether brain-behaviour relationships differed: (i) between diagnostic groups;
      and (ii) as a function of age. We found that total cortical and ventricular
      volume had the greatest number of significant behavioural associations, and
      included correlations with measures from multiple cognitive domains, particularly
      declarative and working memory and executive function. Cortical thickness
      measures, in contrast, showed more specific associations with declarative memory,
      letter fluency and processing speed tasks. While the majority of brain-behaviour
      relationships were similar across diagnostic groups, increased cortical thickness
      in ventrolateral prefrontal and parietal cortical regions was associated with
      better declarative memory only in bipolar disorder subjects, and not in non
      bipolar disorder family members. Additionally, while age had a relatively strong
      impact on all neurocognitive traits, the effects of age on cognition did not
      differ between diagnostic groups. Most brain-behaviour associations were also
      similar across the age range, with the exception of cortical and ventricular
      volume and lingual gyrus thickness, which showed weak correlations with verbal
      fluency and inhibitory control at younger ages that increased in magnitude in
      older subjects, regardless of diagnosis. Findings indicate that neuroanatomical
      traits potentially impacted by bipolar disorder are significantly associated with
      multiple neurobehavioural domains. Structure-function relationships are generally
      preserved across diagnostic groups, with the notable exception of ventrolateral
      prefrontal and parietal association cortex, volumetric increases in which may be
      associated with cognitive resilience specifically in individuals with bipolar
      disorder. Although age impacted all neurobehavioural traits, we did not find any
      evidence of accelerated cognitive decline specific to bipolar disorder subjects.
      Regardless of diagnosis, greater global brain volume may represent a protective
      factor for the effects of ageing on executive functioning. 

PMID- 25943424
TI  - Mashhad stroke and heart atherosclerotic disorder (MASHAD) study: design,
      baseline characteristics and 10-year cardiovascular risk estimation.
AB  - OBJECTIVE: The Mashhad stroke and heart atherosclerotic disorder (MASHAD) study
      is a 10-year cohort study that aims to evaluate the impact of various genetic,
      environmental, nutritional and psychosocial risk factors on the incidence of
      cardiovascular events among an urban population in eastern Iran. METHODS: The
      MASHAD study comprises a cohort of 9704 individuals aged 35-65 years using a
      stratified cluster random sampling design. This cohort will be followed up until
      2020, with follow-up examinations being undertaken every 3 years. Ten-year
      cardiovascular disease (CVD) risk estimation was determined using NCEP ATP III
      criteria. RESULTS: Overall, 88.4 % of women and 79.2 % of men (P < 0.001) had at
      least one lipid abnormality. The 10-year risk for CVD of <10, 10-20 and >20 %
      were observed to be 86.6, 11 and 2.5 %, respectively. Predicted risk of CVD > 10
      % using the Framingham algorithm was considerably higher in men compared to
      women. Overall, 9.5 % [95 % confidence interval (CI) 8.9-10.1 %] of our subjects
      had prevalent CAD. CONCLUSION: The prevalence of CVD risk factors within our
      population is high compared to Western countries, indicating the necessity for
      interventional risk modifications.

PMID- 25943425
TI  - Laparoscopic radical right hemicolectomy for cecal cancer and middle colic artery
      aneurysm.
AB  - BACKGROUND: Middle colic artery (MCA) aneurysms are very rare and exclusively
      reported with symptoms or rupture. We report successful laparoscopic elective
      surgery for both cecal cancer and MCA aneurysm in an 87-year-old man who
      presented with bloody stools. METHODS: Diagnostic colonoscopy revealed a cecal
      tumor 40 mm in diameter that was histologically confirmed as a well
      differentiated adenocarcinoma. The three-phase dynamic computed tomography showed
      a cecal tumor without any metastasis and an MCA aneurysm 10 mm in diameter.
      Radical right hemicolectomy with D3 lymph node dissection that included the MCA
      aneurysm was performed. The postoperative course was uneventful, and the patient
      survived without recurrence. CONCLUSIONS: Even though the present patient was
      very elderly, the postoperative course of laparoscopic radical surgery for both
      an MCA aneurysm and cecal cancer was uneventful with good short-term outcomes.

PMID- 25943426
TI  - Third stage of labor risks in velamentous and marginal cord insertion: a
      population-based study.
AB  - OBJECTIVE: To assess whether anomalous cord insertion is associated with risk of
      complications in the third stage of labor. DESIGN: A population-based study.
      SETTING: Norwegian Medical Birth Register. POPULATION: All singleton births
      (gestational age >16 weeks and <45 weeks) during the period 1999-2011 (n =
      738,443 singletons). Deliveries by cesarean were excluded, leaving 628,680
      vaginal singleton deliveries for the analyses. METHODS: Calculation of odds
      ratios for complications in the third stage of labor (postpartum hemorrhage,
      manual delivery of the placenta, curettage) in velamentous and marginal cord
      insertion by logistic regression with adjustment for confounders. MAIN OUTCOME
      MEASURES: Complications in the third stage of labor, postpartum hemorrhage,
      manual placental removal and curettage. RESULTS: Anomalous cord insertion was
      associated with an increased risk of complications in the third stage of labor,
      the risk being higher for velamentous than for marginal insertion. The risks
      persisted after adjusting for possible confounding factors. Velamentous cord
      insertion carried a 5.6% risk of a need for manual removal of the placenta,
      compared with the risk of 1.1% for nonvelamentous insertion (odds ratio = 5.21,
      95% confidence interval 4.71-5.76) in vaginal delivery, and we found increased
      risks of curettage (odds ratio = 3.29, 95% confidence interval 2.87-3.77) and
      postpartum hemorrhage (odds ratio = 2.06, 95% confidence interval 1.77-2.39).
      CONCLUSIONS: Marginal and especially velamentous cord insertion is associated
      with an increased risk of hemorrhage in the third stage of labor, need for manual
      removal of the placenta and curettage. Anomalous cord insertion can be identified
      prenatally and so possibly influence obstetric management.

PMID- 25943427
TI  - Quantifying alosine prey in the diets of marine piscivores in the Gulf of Maine.
AB  - The objectives of this work were to quantify the spatial and temporal
      distribution of the occurrence of anadromous fishes (alewife Alosa
      pseudoharengus, blueback herring Alosa aestivalis and American shad Alosa
      sapidissima) in the stomachs of demersal fishes in coastal waters of the north
      west Atlantic Ocean. Results show that anadromous fishes were detectable and
      quantifiable in the diets of common marine piscivores for every season sampled.
      Even though anadromous fishes were not the most abundant prey, they accounted for
      c. 5-10% of the diet by mass for several marine piscivores. Statistical
      comparisons of these data with fish diet data from a broad-scale survey of the
      north-west Atlantic Ocean indicate that the frequency of this trophic interaction
      was significantly higher within spatially and temporally focused sampling areas
      of this study than in the broad-scale survey. Odds ratios of anadromous predation
      were as much as 460 times higher in the targeted sampling as compared with the
      broad-scale sampling. Analyses indicate that anadromous prey consumption was more
      concentrated in the near-coastal waters compared with consumption of a similar,
      but more widely distributed species, the Atlantic herring Clupea harengus. In the
      context of ecosystem-based fisheries management, the results suggest that even
      low-frequency feeding events may be locally important, and should be incorporated
      into ecosystem models. 

PMID- 25943429
TI  - What are the most important tasks of tutors during the tutorials in hybrid
      problem-based learning curricula?
AB  - BACKGROUND: In problem-based learning, a tutor, the quality of the problems and
      group functioning play a central role in stimulating student learning. This study
      is conducted in a hybrid medical curriculum where problem-based learning is one
      of the pedagogical approaches. The aim of this study was to examine which tutor
      tasks are the most important during the tutorial sessions and thus should be
      promoted in hybrid (and in maybe all) problem-based learning curricula in higher
      education. METHODS: A student (N = 333) questionnaire was used to obtain data
      about the problem-based learning process, combined with the achievement score of
      the students on a multiple-choice exam. Structural equation modeling was used to
      test the fit of different models (two existing models and a new simplified model)
      representing the factors of interest and their relationships, in order to
      determine which tutor characteristics are the most important in the present
      study. RESULTS: A new simplified model is presented, which demonstrates that
      stimulation of active and self-directed learning by tutors enhances the perceived
      case quality and the perceived group functioning. There was no significant effect
      between the stimulation of collaborative learning and perceived group
      functioning. In addition, group functioning was not a significant predictor for
      achievement. CONCLUSIONS: We found that stimulating active and self-directed
      learning are perceived as tutors' most important tasks with regard to perceived
      case quality and group functioning. It is necessary to train and teach tutors how
      they can stimulate active and self-directed learning by students.

PMID- 25943430
TI  - Rapid Low-Temperature 3D Integration of Silicon Nanowires on Flexible Substrates.
AB  - The vertical integration of 1D nanostructures onto the 2D substrates has the
      potential to offer significant performance gains to flexible electronic devices
      due to high integration density, large surface area, and improved light
      absorption and trapping. A simple, rapid, and low temperature transfer bonding
      method has been developed for this purpose. Ultrasonic vibration is used to
      achieve a low temperature bonding within a few seconds, resulting in a polymer
      matrix-free, electrically conducting vertical assembly of silicon nanowires
      (SiNWs) with a graphene/PET substrate. The microscopic structure, and mechanical
      and electrical characteristics of the interface between the transferred SiNW
      array and graphene layer are subsequently investigated, revealing that this
      creates a mechanically robust and electrically Ohmic contact. This newly
      developed ultrasonic transfer bonding technique is also found to be readily
      adaptable for diverse substrates of both metal and polymer. It is therefore
      considered as a valuable technique for integrating 1D vertical nanostructures
      onto the 2D flexible substrates for flexible photovoltaics, energy storage, and
      water splitting systems. 

PMID- 25943428
TI  - Homozygosity mapping reveals novel and known mutations in Pakistani families with
      inherited retinal dystrophies.
AB  - Inherited retinal dystrophies are phenotypically and genetically heterogeneous.
      This extensive heterogeneity poses a challenge when performing molecular
      diagnosis of patients, especially in developing countries. In this study, we
      applied homozygosity mapping as a tool to reduce the complexity given by genetic
      heterogeneity and identify disease-causing variants in consanguineous Pakistani
      pedigrees. DNA samples from eight families with autosomal recessive retinal
      dystrophies were subjected to genome wide homozygosity mapping (seven by SNP
      arrays and one by STR markers) and genes comprised within the detected homozygous
      regions were analyzed by Sanger sequencing. All families displayed consistent
      autozygous genomic regions. Sequence analysis of candidate genes identified four
      previously-reported mutations in CNGB3, CNGA3, RHO, and PDE6A, as well as three
      novel mutations: c.2656C > T (p.L886F) in RPGRIP1, c.991G > C (p.G331R) in CNGA3,
      and c.413-1G > A (IVS6-1G > A) in CNGB1. This latter mutation impacted pre-mRNA
      splicing of CNGB1 by creating a -1 frameshift leading to a premature termination
      codon. In addition to better delineating the genetic landscape of inherited
      retinal dystrophies in Pakistan, our data confirm that combining homozygosity
      mapping and candidate gene sequencing is a powerful approach for mutation
      identification in populations where consanguineous unions are common. 

PMID- 25943431
TI  - Addressing spontaneous signal voids in repetitive single-shot DWI of musculature:
      spatial and temporal patterns in the calves of healthy volunteers and
      consideration of unintended muscle activities as underlying mechanism.
AB  - Single-shot diffusion-weighted MRI sensitive to different types of incoherent
      motion inside tissue shows sporadic signal voids with a considerable size (>1 cm)
      in calf musculature at rest. Spatial and temporal patterns of these signal voids
      and their dependence on measurement conditions were tested systematically in
      order to obtain more insight into the underlying mechanism. Lower leg muscles of
      10 healthy subjects were examined by recording series of 1000 echo-planar single
      shot scans with repetition time 500 ms and b-value 100 s/mm(2) . Effects of
      strength and orientation of motion sensitization gradients and of repetition
      times were analysed. Potential influences of arterial blood pulsations and
      positioning of the subject were studied. Comparison of calf muscle groups showed
      more frequent signal voids in gastrocnemius and soleus muscle compared with
      tibialis muscles. Large inter-individual variance in the total number of signal
      voids visible in a transverse slice of the lower leg was observed (minimum
      40/1000 scans; maximum >550/1000 scans). Typical sizes of the affected muscular
      areas ranged from 1.5 to 2.5 cm in the transverse and from 1.5 to 7 cm in the
      head-feet direction. Signal voids occurred nearly independent of the cardiac
      phase and with similar frequencies for supine and prone positions. Resting calf
      muscles show spontaneous signal voids in single-shot DWI at low b-values with an
      irregular temporal and spatial pattern. Values of mean diffusivity, diffusion
      tensor parameters, and IVIM-derived perfusion are expected to be clearly
      distorted by such signal voids if no rejection of affected data is applied.
      Several potential causes for the signal voids are discussed. The most probable
      explanation for the phenomenon is seen in the occurrence of spontaneous
      incoherent mechanical activity in musculature based on weak muscle fibre
      contractions. If this is the case it opens up a new field for studies on the
      physiological role and regulation of these unintended muscle activities.

PMID- 25943432
TI  - Index for Predicting Insurance Claims from Wind Storms with an Application in
      France.
AB  - For insurance companies, wind storms represent a main source of volatility,
      leading to potentially huge aggregated claim amounts. In this article, we compare
      different constructions of a storm index allowing us to assess the economic
      impact of storms on an insurance portfolio by exploiting information from
      historical wind speed data. Contrary to historical insurance portfolio data,
      meteorological variables show fewer nonstationarities between years and are
      easily available with long observation records; hence, they represent a valuable
      source of additional information for insurers if the relation between
      observations of claims and wind speeds can be revealed. Since standard
      correlation measures between raw wind speeds and insurance claims are weak, a
      storm index focusing on high wind speeds can afford better information. A storm
      index approach has been applied to yearly aggregated claim amounts in Germany
      with promising results. Using historical meteorological and insurance data, we
      assess the consistency of the proposed index constructions with respect to
      various parameters and weights. Moreover, we are able to place the major
      insurance events since 1998 on a broader horizon beyond 40 years. Our approach
      provides a meteorological justification for calculating the return periods of
      extreme-storm-related insurance events whose magnitude has rarely been reached. 

PMID- 25943433
TI  - Pathways Through Care for Long-Term Pain After Knee Replacement: A Qualitative
      Study With Healthcare Professionals.
AB  - BACKGROUND: Chronic pain after total knee replacement is experienced by around
      20% of patients in the UK. Ensuring that services are designed to best meet the
      needs of patients requires a foundation of empirical work. The present study
      sought to describe healthcare professionals' experiences and views on the
      assessment and care of patients with chronic pain after total knee replacement.
      METHODS: We undertook a qualitative focus group study with healthcare
      professionals at a large acute NHS hospital trust, all of whom came into contact
      with patients experiencing chronic pain after total knee replacement. Snowball
      sampling was used to recruit participants to four focus groups. Transcripts of
      the audio-recorded groups were analysed thematically. RESULTS: Eighteen
      healthcare professionals from a range of disciplines took part. Participants
      found it difficult to conceptualize chronic pain; its character varied between
      patients, and its origins and progress were often ambiguous. In the first of two
      superordinate themes, participants recognized chronic pain as a possible outcome
      of total knee replacement, but felt that patients may be unprepared for this. In
      the second superordinate theme, apparent complexities in assessing and managing
      patients with chronic pain after total knee replacement and a lack of explicit
      access points meant that healthcare professionals often saw no clear way to help
      patients. Participants agreed that a multidisciplinary approach that adapts to
      individual patient context was an ideal approach. CONCLUSION: The present study
      illustrated potential obstacles to 'best practice' in the management of chronic
      pain after total knee replacement, identified through research with healthcare
      professionals. There is a need to improve access to services and develop well
      defined and flexible care pathways that can accommodate complexities inherent to
      chronic pain, such as an unpredictable course. Copyright (c) 2015 John Wiley &
      Sons, Ltd.

PMID- 25943434
TI  - Evaluation of porcine epidemic diarrhea virus transmission and the immune
      response in growing pigs.
AB  - Clinical disease associated with porcine epidemic diarrhea virus (PEDV) infection
      in naive pigs is well chronicled; however, information on endemic PEDV infection
      is limited. To characterize chronic PEDV infection, the duration of infectious
      virus shedding and development of protective immunity was determined. On Day 0
      (D0), a growing pig was challenged with PEDV and 13 contacts were commingled. On
      D7, 9 contact pigs (principal virus group (PG)), were selected, moved to a
      separate room and commingled with one sentinel pig (S1). This process was
      repeated weekly with S2, S3 and S4. The PG was PEDV-positive by PCR from D3-11,
      with some pigs intermittently positive to D42. Pigs S1 and S2 were PEDV-positive
      within 24 hours of commingling. Antibodies were detected in all PG by D21 and by
      7 days post-contact in S1 and S2. Pigs S3 and S4 were PCR and antibody negative
      following commingling. To evaluate protective immunity, 5 naive pigs (N) and the
      PG were challenged (N/C, PG/C) with homologous virus on D49. All N/C pigs were
      PEDV PCR-positive by D52 with detection out to D62 in 3/5 N/C pigs. All PG/C pigs
      were PEDV PCR-negative post-challenge. By D63, all N/C seroconverted. Although
      PEDV RNA was demonstrated in pigs after primary infection until D42, infectious
      PEDV capable of horizontal transmission to naive pigs was only shed 14-16 days
      after infection to age-matched pigs. Homologous re-challenge 49 days post initial
      PEDV exposure did not result in re-infection of the pigs. This demonstrates
      potential for an effective PEDV vaccine. 

PMID- 25943436
TI  - E-assessment and an e-training program among elderly care staff lacking formal
      competence: results of a mixed-methods intervention study.
AB  - BACKGROUND: Among staff working in elderly care, a considerable proportion lack
      formal competence for their work. Lack of formal competence, in turn, has been
      linked to higher staff ratings of stress symptoms, sleep disturbances and
      workload. OBJECTIVES: 1) To describe the strengths and weaknesses of an e
      assessment and subsequent e-training program used among elderly care staff who
      lack formal competence and 2) to study the effects of an e-training program on
      staff members' working life (quality of care and psychological and structural
      empowerment) and well-being (job satisfaction and psychosomatic health). The
      hypothesis was that staff who had completed the e-assessment and the e-training
      program would rate greater improvements in working life and well-being than would
      staff who had only participated in the e-assessments. METHODS: An intervention
      study with a mixed-methods approach using quantitative (2010-2011) and
      qualitative data (2011) was conducted in Swedish elderly care. Participants
      included a total of 41 staff members. To describe the strengths and weaknesses of
      the e-assessment and the e-training program, qualitative data were gathered using
      semi-structured interviews together with a study-specific questionnaire. To study
      the effects of the intervention, quantitative data were collected using
      questionnaires on: job satisfaction, psychosomatic health, psychological
      empowerment, structural empowerment and quality of care in an intervention and a
      comparison group. RESULTS: Staff who completed the e-assessments and the e
      training program primarily experienced strengths associated with this approach.
      The results were also in line with our hypotheses: Staff who completed the e
      assessment and the e-training program rated improvements in their working life
      and well-being. CONCLUSION: Use of the e-assessments and e-training program
      employed in the present study could be one way to support elderly care staff who
      lack formal education by increasing their competence; increased competence, in
      turn, could improve their self-confidence, working life, and well-being.

PMID- 25943435
TI  - QF2011: a protocol to study the effects of the Queensland flood on pregnant
      women, their pregnancies, and their children's early development.
AB  - BACKGROUND: Retrospective studies suggest that maternal exposure to a severe
      stressor during pregnancy increases the fetus' risk for a variety of disorders in
      adulthood. Animal studies testing the fetal programming hypothesis find that
      maternal glucocorticoids pass through the placenta and alter fetal brain
      development, particularly the hypothalamic-pituitary-adrenal axis. However, there
      are no prospective studies of pregnant women exposed to a sudden-onset
      independent stressor that elucidate the biopsychosocial mechanisms responsible
      for the wide variety of consequences of prenatal stress seen in human offspring.
      The aim of the QF2011 Queensland Flood Study is to fill this gap, and to test the
      buffering effects of Midwifery Group Practice, a form of continuity of maternity
      care. METHODS/DESIGN: In January 2011 Queensland, Australia had its worst
      flooding in 30 years. Simultaneously, researchers in Brisbane were collecting
      psychosocial data on pregnant women for a randomized control trial (the M@NGO
      Trial) comparing Midwifery Group Practice to standard care. We invited these and
      other pregnant women to participate in a prospective, longitudinal study of the
      effects of prenatal maternal stress from the floods on maternal, perinatal and
      early childhood outcomes. Data collection included assessment of objective
      hardship and subjective distress from the floods at recruitment and again 12
      months post-flood. Biological samples included maternal bloods at 36 weeks
      pregnancy, umbilical cord, cord blood, and placental tissues at birth.
      Questionnaires assessing maternal and child outcomes were sent to women at 6
      weeks and 6 months postpartum. The protocol includes assessments at 16 months,
      21/2 and 4 years. Outcomes include maternal psychopathology, and the child's
      cognitive, behavioral, motor and physical development. Additional biological
      samples include maternal and child DNA, as well as child testosterone, diurnal
      and reactive cortisol. DISCUSSION: This prenatal stress study is the first of its
      kind, and will fill important gaps in the literature. Analyses will determine the
      extent to which flood exposure influences the maternal biological stress response
      which may then affect the maternal-placental-fetal axis at the biological,
      biochemical, and molecular levels, altering fetal development and influencing
      outcomes in the offspring. The role of Midwifery Group Practice in moderating
      effects of maternal stress will be tested.

PMID- 25943437
TI  - Lung MRI and impairment of diaphragmatic function in Pompe disease.
AB  - BACKGROUND: Pompe disease is a progressive metabolic myopathy. Involvement of
      respiratory muscles leads to progressive pulmonary dysfunction, particularly in
      supine position. Diaphragmatic weakness is considered to be the most important
      component. Standard spirometry is to some extent indicative but provides too
      little insight into diaphragmatic dynamics. We used lung MRI to study
      diaphragmatic and chest-wall movements in Pompe disease. METHODS: In ten adult
      Pompe patients and six volunteers, we acquired two static spirometer-controlled
      MRI scans during maximum inspiration and expiration. Images were manually
      segmented. After normalization for lung size, changes in lung dimensions between
      inspiration and expiration were used for analysis; normalization was based on the
      cranial-caudal length ratio (representing vertical diaphragmatic displacement),
      and the anterior-posterior and left-right length ratios (representing chest-wall
      movements due to thoracic muscles). RESULTS: We observed striking dysfunction of
      the diaphragm in Pompe patients; in some patients the diaphragm did not show any
      displacement. Patients had smaller cranial-caudal length ratios than volunteers
      (p < 0.001), indicating diaphragmatic weakness. This variable strongly correlated
      with forced vital capacity in supine position (r = 0.88) and postural drop (r =
      0.89). While anterior-posterior length ratios also differed between patients and
      volunteers (p = 0.04), left-right length ratios did not (p = 0.1). CONCLUSIONS:
      MRI is an innovative tool to visualize diaphragmatic dynamics in Pompe patients
      and to study chest-walland diaphragmatic movements in more detail. Our data
      indicate that diaphragmatic displacement may be severely disturbed in patients
      with Pompe disease.

PMID- 25943439
TI  - Tandem Duplication and Random Loss for mitogenome rearrangement in Symphurus
      (Teleost: Pleuronectiformes).
AB  - BACKGROUND: The mitochondrial genomes (mitogenomes) of flatfishes
      (Pleuronectiformes) exhibit highly diversified types of large-scale gene
      rearrangements. We have reported that the mitogenomes of Crossorhombus azureus
      (Bothidae), Samariscus latus (Samaridae) and Cynoglossus fishes (Cynoglossidae)
      show different types of gene rearrangements. RESULTS: In the present study, the
      complete mitogenomes of two Symphurus species (Cynoglossidae), Symphurus plagiusa
      and Symphurus orientalis, were determined. The gene order in the S. plagiusa
      mitogenome is the same as that of a typical vertebrate (without any gene
      rearrangements). Surprisingly, large-scale gene rearrangements have occurred in
      S. orientalis. In the rearranged fragment from the control region (CR) to the
      WANCY tRNA cluster (tRNA cluster of tRNA-W, tRNA-A, tRNA-N, tRNA-C and tRNA-Y) in
      the S. orientalis mitogenome, tRNA-V and tRNA-M have been translocated to the 3'
      end of the 16S rRNA gene, with six large intergenic spacers over 20 bp in length.
      In addition, an origin for light-strand replication (OL) structure that is
      typically located in the WANCY region was absent in both the S. plagiusa and S.
      orientalis mitogenomes. It is generally recognized that a sequence in the WANCY
      region that encodes tRNAs forms a hairpin structure (OL-like structure) and can
      act as the OL when the typical locus is lost. Moreover, an additional OL-like
      structure was identified near the control region in the S. plagiusa mitogenome.
      CONCLUSIONS: The positions of the intergenic spacers and the rearranged genes of
      the S. orientalis mitogenome strongly indicate that the mechanism underlying the
      rearrangement of this mitogenome was Tandem Duplication and Random Loss.
      Additionally, two OL-like regions substituting for the typical locus were found
      in the S. plagiusa mitogenome. We speculate that the ancestral mitogenomes of S.
      plagiusa and S. orientalis also had this characteristic, such that if both OL
      like structures functioned during mitochondrial replication, they could initiate
      duplicate replications of the light strand (L-strand), leading to duplication of
      the region between the two structures. We consider that this mechanism may
      account for the gene duplication that occurred during the gene rearrangement
      process in the evolution of the ancestral mitogenome to the S. orientalis
      mitogenome.

PMID- 25943440
TI  - The effect of upper-extremity aerobic exercise on complex regional pain syndrome
      type I: a randomized controlled study on subacute stroke.
AB  - BACKGROUND AND PURPOSE: Complex regional pain syndrome type I (CPRS I), is a
      complex of symptoms characterized by diffuse pain usually with associated
      swelling, vasomotor instability, and severe functional impairment of the affected
      extremity in stroke patients. Pain is a prominent feature and is often refractory
      to variety of treatment. METHODS: To investigate the clinical, functional, and
      psychosocial effects of upper extremity aerobic exercise (UEAE) and compare the
      effect of aerobic exercise with that of conventional physiotherapy in patients
      with CPRS type I following stroke as a randomized controlled assesor blinded 4 
      week-study. A total of 52 inpatients with stroke [mean age: 65.95 +/- 8.7 (min. =
      53, max. = 80) years, and the mean age of the control group was 67.50 +/- 11.2
      years], all within 6  months post-stroke and diagnosed with CPRS I. The UEAE
      program consisted of an arm crank ergometer (10  W/min), in addition to a
      conventional physiotherapy (whirlpool, TENS, retrograd massage). Primary outcome
      measures were CPRS clinical determinants (pain, hyperalgesia, allodynia, and
      autonomic abnormalities) secondary outcome measures were functional independence
      measure (FIM), Nottingham Health Profile (NHP), and Beck Depression Scale scores
      that were performed at 0  month (baseline) and 4  weeks (post-treatment).
      RESULTS: In UEAE group, patients reported significant pain relief (89.9%) and
      significant decline in CRPS signs and symptoms. The mean change in pain at
      shoulder, pain at the hand as well as and NHP and BDS scores between groups were
      statistically significant (P < 0.05). CONCLUSIONS: UEAE made an excellent
      improvement in the symptoms and signs of CRPS I. Combined treatment of
      conventional physiotherapy and aerobic exercises may be an excellent synthesis
      for this syndrome in these patients.

PMID- 25943442
TI  - Synthetic investigation of glycine catalyzed triarylimidazole based
      organophosphorous heterocyclic functionalized vinyl polymer - A green approach.
AB  - In the present investigation, an efficient and environmentally adopted synthesis
      of triaryl substituted imidazole in one-pot was reported. The multicomponent
      reaction between various aldehydes, benzil, benzoin, ammonium acetate and glycine
      under solvent free condition has been explained. Instead of using toxic reagents
      for the synthesis of heterocyclic compounds, Glycine has been selected as a green
      catalyst due to simple work-up procedure, shorter reaction time and high yield.
      The synthesized imidazole derivatives on further treatment with phosphorous
      oxychloride resulted in an organophosphorous containing N-heterocyclic compound
      (N-P) thus by altering acidic hydrogen of imidazole. Further, N-P was reacted
      with polyvinyl alcohol resulted into organophosphorous N-heterocyclic vinyl
      polymers. The synthesized vinyl polymers were characterized using, FTIR, NMR and
      Mass spectral studies. Results of the spectral studies were well supported the
      formation of the compounds. Thermal stability have also been studied using TGA. 

PMID- 25943444
TI  - Primary renal osteosarcoma: a very rare tumour with an ominous prognosis.

PMID- 25943443
TI  - Outcomes of patients with lymph node metastasis treated with radical
      prostatectomy and adjuvant androgen deprivation therapy in a Chinese population:
      results from a cohort study.
AB  - BACKGROUND: The aim of this study is to assess the prognosis of prostate cancer
      (PCa) with lymph node metastases (LNM) detected in pelvic lymph node dissection
      (PLND) after radical prostatectomy (RP) and adjuvant androgen deprivation therapy
      (ADT) in a Chinese population. METHODS: From June 2005 to September 2012, the
      medical histories of 67 Chinese PCa patients with LNM detected after RP and
      extended PLND were collected, and all these patients received continuous adjuvant
      ADT. Postoperative survival was estimated using the Kaplan-Meier method. The
      impact of various clinicopathological factors on outcome was analyzed using Cox
      proportional hazard regression models. All tests were two-sided with P < 0.05
      considered significant. RESULTS: Median follow-up was 46.7 months, and two
      patients were lost to follow-up. Five-year event-free survival for patients with
      positive lymph nodes was 93.0%, 83.0%, and 96.0% for local recurrence, systemic
      progression, and cancer death, respectively. One-year, 2-year, and 3-year
      biochemical recurrence (BCR)-free survival was 52%, 40%, and 22%, respectively.
      Postoperative BCR-free survival was 25.7 months. BCR-free survival for patients
      with a single LNM was longer than those with two or more LNM (median 39.1 months
      vs. median 17.2 months, P = 0.002). In a multivariate Cox model, only two or more
      LNM was a significant predictor of BCR (hazard ratio 2.6, P = 0.005).
      CONCLUSIONS: Despite low BCR-free survival, Chinese patients with LNM can benefit
      from RP and adjuvant ADT. Patients with low nodal metastatic burden had a
      favorable prognosis.

PMID- 25943445
TI  - (1)H MR spectroscopic imaging of the prostate at 7T using spectral-spatial
      pulses.
AB  - PURPOSE: To assess the feasibility of prostate (1)H MR spectroscopic imaging
      (MRSI) using low-power spectral-spatial (SPSP) pulses at 7T, exploiting accurate
      spectral selection and spatial selectivity simultaneously. METHODS: A double spin
      echo sequence was equipped with SPSP refocusing pulses with a spectral
      selectivity of 1 ppm. Three-dimensional prostate (1)H-MRSI at 7T was performed
      with the SPSP-MRSI sequence using an 8-channel transmit array coil and an
      endorectal receive coil in three patients with prostate cancer and in one healthy
      subject. No additional water or lipid suppression pulses were used. RESULTS:
      Prostate (1)H-MRSI could be obtained well within specific absorption rate (SAR)
      limits in a clinically feasible time (10 min). Next to the common citrate
      signals, the prostate spectra exhibited high spermine signals concealing creatine
      and sometimes also choline. Residual lipid signals were observed at the edges of
      the prostate because of limitations in spectral and spatial selectivity.
      CONCLUSION: It is possible to perform prostate (1)H-MRSI at 7T with a SPSP-MRSI
      sequence while using separate transmit and receive coils. This low-SAR MRSI
      concept provides the opportunity to increase spatial resolution of MRSI within
      reasonable scan times.

PMID- 25943447
TI  - Routine characterization of biomarkers in non-small cell lung carcinoma: how much
      is enough?

PMID- 25943446
TI  - Genome-wide characterization and expression profiling of immune genes in the
      diamondback moth, Plutella xylostella (L.).
AB  - The diamondback moth, Plutella xylostella (L.), is a destructive pest that
      attacks cruciferous crops worldwide. Immune responses are important for
      interactions between insects and pathogens and information on these underpins the
      development of strategies for biocontrol-based pest management. Little, however,
      is known about immune genes and their regulation patterns in P. xylostella. A
      total of 149 immune-related genes in 20 gene families were identified through
      comparison of P. xylostella genome with the genomes of other insects. Complete
      and conserved Toll, IMD and JAK-STAT signaling pathways were found in P.
      xylostella. Genes involved in pathogen recognition were expanded and more
      diversified than genes associated with intracellular signal transduction. Gene
      expression profiles showed that the IMD pathway may regulate expression of
      antimicrobial peptide (AMP) genes in the midgut, and be related to an observed
      down-regulation of AMPs in experimental lines of insecticide-resistant P.
      xylostella. A bacterial feeding study demonstrated that P. xylostella could
      activate different AMPs in response to bacterial infection. This study has
      established a framework of comprehensive expression profiles that highlight cues
      for immune regulation in a major pest. Our work provides a foundation for further
      studies on the functions of P. xylostella immune genes and mechanisms of innate
      immunity. 

PMID- 25943448
TI  - Omalizumab: a treatment for severe asthma in real life?

PMID- 25943449
TI  - Erratum to "The future of lung transplantation".

PMID- 25943450
TI  - Patients' participation in decision-making in the medical field-
      'projectification' of patients in a neoliberal framed healthcare system.
AB  - This article focuses on patients' participation in decision-making in meetings
      with healthcare professionals in a healthcare system, based on neoliberal
      regulations and ideas. Drawing on two constructed empirical cases, primarily from
      the perspective of patients, this article analyses and discusses the clinical
      practice around decision-making meetings within a Foucauldian perspective.
      Patients' participation in decision-making can be seen as an offshoot of respect
      for patient autonomy. A treatment must be chosen, when patients consult
      physicians. From the perspective of patients, there is a tendency for healthcare
      professionals to supply the patients with the information that they think are
      necessary for them to make their own decision. But patients do not always want to
      be a 'customer' in the healthcare system; they want to be a patient, consulting
      an expert for help and advice, which creates resistance to some parts of the
      decision-making process. Both professionals and patients are subject to the
      structural frame of the medical field, formed of both neoliberal framework and
      medical logic. The decision-making competence in relation to the choice of
      treatment is placed away from the professionals and seen as belonging to the
      patient. A 'projectification' of the patient occurs, whereby the patient becomes
      responsible for his/her choices in treatment and care and the professionals
      support him/her with knowledge, preferences, and alternative views, out of which
      he/she must make his/her own choices, and the responsibility for those choices
      now and in the future. At the same time, there is a tendency towards de
      professionalization. In that light, participation of patients in decision-making
      can be regarded as a tacit governmentality strategy that shapes the location of
      responsibility between individual and society, and independent patients and
      healthcare professionals, despite the basically desirable, appropriate, and
      necessary idea of involving patients in their own situations from a humanistic
      perspective. 

PMID- 25943451
TI  - Autologous alternative veins may not provide better outcomes than prosthetic
      conduits for below-knee bypass when great saphenous vein is unavailable.
AB  - BACKGROUND: There is a need to better define the role of alternative autologous
      vein (AAV) segments over contemporary prosthetic conduits in patients with
      critical limb ischemia when great saphenous vein (GSV) is not available for use
      as the bypass conduit. METHODS: Consecutive patients who underwent bypass to
      infrageniculate targets between 2007 and 2011 were categorized in three groups:
      GSV, AAV, and prosthetic. The primary outcome was graft patency. The secondary
      outcome was limb salvage. Cox proportional hazards regression was used to adjust
      for baseline confounding variables. RESULTS: A total of 407 infrainguinal
      bypasses to below-knee targets were analyzed; 255 patients (63%) received a
      single-segment GSV, 106 patients (26%) received an AAV, and 46 patients (11%)
      received a prosthetic conduit. Baseline characteristics were similar among
      groups, with the exception of popliteal targets and anticoagulation use being
      more frequent in the prosthetic group. Primary patency at 2 and 5 years was
      estimated at 47% and 32%, respectively, for the GSV group; 24% and 23% for the
      AAV group; and 43% and 38% for the prosthetic group. Primary assisted patency at
      2 and 5 years was estimated at 71% and 55%, respectively, for the GSV group; 53%
      and 51% for the AAV group; and 45% and 40% for the prosthetic group. Secondary
      patency at 2 and 5 years was estimated at 75% and 60%, respectively, for the GSV
      group; 57% and 55% for the AAV group; and 46% and 41% for the prosthetic group.
      In Cox analysis, primary patency (hazard ratio [HR], 0.55; P < .001; 95%
      confidence interval [CI], 0.404-0.758), primary assisted patency (HR, 0.57; P =
      .004; 95% CI, 0.388-0.831), and secondary patency (HR, 0.56; P = .005; 95% CI,
      0.372-0.840) were predicted by GSV compared with AAV, but there was no difference
      between AAV and prosthetic grafts except for the primary patency, for which
      prosthetic was protective (HR, 0.38; P < .001; 95% CI, 0.224-0.629). Limb salvage
      was similar among groups. CONCLUSIONS: AAV conduits may not offer a significant
      patency advantage in midterm follow-up over prosthetic bypasses.

PMID- 25943452
TI  - Outcome after open and endovascular repairs of abdominal aortic aneurysms in
      matched cohorts using propensity score modeling.
AB  - OBJECTIVE: The objective of this study was to compare outcomes after open repair
      (OR) vs endovascular aneurysm repair (EVAR) of infrarenal abdominal aortic
      aneurysms (AAAs). METHODS: Clinical data of consecutive patients treated for
      asymptomatic AAA between 2000 and 2011 were reviewed. Patients were stratified
      into low/normal-risk (comorbidity score <= 10) and high-risk (score > 10)
      categories. The primary end point was all-cause mortality; secondary end points
      were complications, reinterventions, conversions, and ruptures. Propensity score
      based matching was performed to compare outcomes. RESULTS: There were 1534
      patients, of whom 207 were women (13%); 641 (42%) were treated with OR and 893
      (58%) with EVAR. After propensity score matching, we selected 558 pairs of OR and
      EVAR (mean age, 73 +/- 7.6 years); 158 were women (14%). The 30-day mortality
      rate was 1.3% after OR and 0.9% after EVAR (P = .56). In multivariable analysis,
      only high risk was an independent predictor of early mortality (odds ratio, 4.65;
      95% confidence interval [CI], 1.20-18; P = .03). The early complication rate was
      lower for EVAR (13%; odds ratio, 0.5; 95% CI, 0.4-0.8; P < .001) than for OR
      (24%). Median follow-up was 7.6 years (31 days-13.1 years). The cumulative 5-year
      survival rate was 72% after EVAR and 81% after OR (hazard ratio, 1.44; 95% CI,
      1.19-1.73; P < .001). The 5-year survival was not significantly different in
      matched cohorts operated on after 2005 (77% vs 81%; P = .57). High risk, advanced
      age, cancer history, AAA size, and EVAR predicted all-cause mortality. Freedom
      from reintervention was 74% after EVAR and 88% after OR (hazard ratio, 2.60; 95%
      CI, 1.92-3.51; P < .001). Freedom from rupture was 99.2% after EVAR and 99.8%
      after OR (P = .04). In multivariable models, female gender was associated with
      complications; EVAR was associated with reinterventions (P < .05). CONCLUSIONS:
      In this retrospective propensity score-matched study, early mortality was
      similarly low after both EVAR and OR, significantly different from all except one
      large randomized controlled trial. EVAR had fewer early complications, but it was
      associated with late all-cause mortality and reinterventions and had a small but
      definite risk of late rupture. Significantly increased mortality at 5 years was
      no longer observed when operations were performed after 2005. High risk, advanced
      age, cancer history, and AAA size predicted late all-cause mortality. This study
      failed to confirm early or late survival benefit for EVAR vs OR. Improved
      surveillance, longer follow-up, and analysis of factors affecting late death in
      prospective studies are warranted.

PMID- 25943453
TI  - The Vascular Surgical Milestones Project.

PMID- 25943455
TI  - Results of complex aortic stent grafting of abdominal aortic aneurysms stratified
      according to the proximal landing zone using the Society for Vascular Surgery
      classification.
AB  - BACKGROUND: Advances in endovascular technology have led to the successful
      treatment of complex abdominal aortic aneurysms. However, there is currently no
      consensus on what constitutes a juxtarenal, pararenal, or suprarenal aneurysm.
      There is emerging evidence that the extent of the aneurysm repair is associated
      with outcome. We compare the outcomes of 150 consecutive patients treated with a
      fenestrated or branched stent graft and present the data stratified according to
      the Society for Vascular Surgery classification based on proximal anatomic
      landing zones. METHODS: A prospectively collected database of consecutive
      patients undergoing fenestrated or branched stent graft insertion in a tertiary
      center between 2008 and 2013 was retrospectively analyzed. Aneurysms were
      subdivided into zones according to where the area of proximal seal could be
      achieved in relation to the visceral arteries. Zone 8 covers the renal arteries,
      zone 7 covers the superior mesenteric artery, and zone 6 covers the celiac axis.
      Patient demographics, operative variables, mortality, and major morbidity were
      analyzed by univariate and multivariate analysis to assess for differences
      between zones. RESULTS: During the study period, 150 patients were treated. There
      were 49 in zone 8, 76 in zone 7, and 25 in zone 6. Prior aortic surgery had been
      performed in 19 patients, which included 11 patients with previous endovascular
      aneurysm repairs. There was significantly increased blood loss (P < .001),
      operative time (P < .0001), total hospital stay (P = .018), and intensive care
      unit stay (P < .0001) as the zones ascended the aorta. There were 14 inpatient
      deaths recorded across all zones with a 30-day mortality rate of 8%. Logistic
      regression analysis for 30 day mortality showed a significant increase as the
      zones ascended (P = .007). Kaplan-Meier analysis showed that 5-year survival
      significantly deteriorated as the zones ascended (P = .039), with no significant
      difference in the freedom from reintervention curves between zones (P = .37).
      CONCLUSIONS: We have shown that the extent of the aneurysm repair as determined
      by the proximal sealing zone is associated with outcome. Mortality, operative
      duration, blood loss, and hospital stay all significantly increased as the zones
      ascended. These data also validate the use of the proposed new classification
      based on aortic anatomy.

PMID- 25943454
TI  - The effect of endovascular treatment on isolated iliac artery aneurysm treatment
      and mortality.
AB  - OBJECTIVE: Isolated iliac artery aneurysms are rare, but potentially fatal. The
      effect of recent trends in the use of endovascular iliac aneurysm repair (EVIR)
      on isolated iliac artery aneurysm-associated mortality is unknown. METHODS: We
      identified all patients with a primary diagnosis of iliac artery aneurysm in the
      National Inpatient Sample from 1988 to 2011. We examined trends in management
      (open vs EVIR, elective and urgent) and overall isolated iliac artery aneurysm
      related deaths (with or without repair). We compared in-hospital mortality and
      complications for the subgroup of patients undergoing elective open and EVIR from
      2000 to 2011. RESULTS: We identified 33,161 patients undergoing isolated iliac
      artery aneurysm repair from 1988 to 2011, of which there were 9016 EVIR and 4933
      open elective repairs from 2000 to 2011. Total repairs increased after the
      introduction of EVIR, from 28 to 71 per 10 million United States (U.S.)
      population (P < .001). EVIR surpassed open repair in 2003. Total isolated iliac
      artery aneurysm-related deaths, due to rupture or elective repair, decreased
      after the introduction of EVIR from 4.4 to 2.3 per 10 million U.S. population (P
      < .001). However, urgent admissions did not decrease during this time period (15
      to 15 procedures per 10 million U.S. population; P = .30). Among elective repairs
      after 2000, EVIR patients were older (72.4 vs 69.4 years; P = .002) and were more
      likely to have a history of prior myocardial infarction (14.0% vs 11.3%; P <
      .001) and renal failure (7.2% vs 3.6%; P < .001). Open repair had significantly
      higher rate of in-hospital mortality (1.8% vs 0.5%; P < .001) and complications
      (17.9% vs 6.7%; P < .001) and a longer length of stay (6.7 vs 2.3 days; P <
      .001). CONCLUSIONS: Treatment of isolated iliac artery aneurysms has increased
      since the introduction of EVIR and is associated with lower perioperative
      mortality, despite a higher burden of comorbid illness. Decreasing iliac artery
      aneurysm-attributable in-hospital deaths are likely related primarily to lower
      elective mortality with EVIR rather than rupture prevention.

PMID- 25943456
TI  - Betacellulin transgenic mice develop urothelial hyperplasia and show sex
      dependent reduction in urinary major urinary protein content.
AB  - The epidermal growth factor (EGF)-like ligands and their cognate ERBB1-4
      receptors represent important signaling pathways that regulate tissue and cell
      proliferation, differentiation and regeneration in a wide variety of tissues,
      including the urogenital tract. Betacellulin (BTC) can activate all four ERBB
      tyrosine kinase receptors and is a multifunctional EGF-like ligand with diverse
      roles in beta cell differentiation, bone maturation, formation of functional
      epithelial linings and vascular permeability in different organs. Using
      transgenic BTC mice, we have studied the effect of constitutive systemic BTC over
      expression on the urinary bladder. BTC was detected in microvascular structures
      of the stromal bladder compartment and in umbrella cells representing the
      protective apical lining of the uroepithelium. ERBB1 and ERBB4 receptors were co
      localized in the urothelium. Mice transgenic for BTC and double transgenic for
      both BTC and the dominant kinase-dead mutant of EGFR (Waved 5) developed
      hyperplasia of the uroepithelium at 5months of age, suggesting that urothelial
      hyperplasia was not exclusively dependent on ERBB1/EGFR. Mass spectrometric
      analysis of urine revealed a significant down-regulation of major urinary
      proteins in female BTC transgenic mice, suggesting a novel role for systemic BTC
      in odor-based signaling in female transgenic BTC mice.

PMID- 25943457
TI  - Assessing prevention measures and Sin Nombre hantavirus seroprevalence among
      workers at Yosemite National Park.
AB  - BACKGROUND: During 2012, a total of 10 overnight visitors to Yosemite National
      Park (Yosemite) became infected with a hantavirus (Sin Nombre virus [SNV]); three
      died. SNV infections have been identified among persons with occupational
      exposure to deer mice (Peromyscus maniculatus). METHODS: We assessed SNV
      infection prevalence, work and living environments, mice exposures, and SNV
      prevention training, knowledge, and practices among workers of two major
      employers at Yosemite during September-October, 2012 by voluntary blood testing
      and a questionnaire. RESULTS: One of 526 participants had evidence of previous
      SNV infection. Participants reported frequently observing rodent infestations at
      work and home and not always following prescribed safety practices for tasks,
      including infestation cleanup. CONCLUSION: Although participants had multiple
      exposures to deer mice, we did not find evidence of widespread SNV infections.
      Nevertheless, employees working around deer mice should receive appropriate
      training and consistently follow prevention policies for high-risk activities.

PMID- 25943459
TI  - Expression of apoptosis-related genes in the mouse skin during the first
      postnatal catagen stage, focused on localization of Bnip3L and caspase-12.
AB  - Hair follicles undergo repetitive stages of cell proliferation and programmed
      cell death. The catagen stage of physiological apoptosis is connected with
      dynamic changes in morphology and alterations in gene expression. However, hair
      follicle apoptosis must be in balance with events in surrounding tissues, such as
      keratinocyte cornification, to maintain complex skin homeostasis. Several pro-
      and anti-apoptotic molecules in the skin have been reported but mainly in
      pathological states. In this investigation, apoptosis-related gene expression was
      examined during the first catagen stage of mouse hair follicle development by PCR
      arrays under physiological conditions. Postnatal stages P15 and P17, representing
      early and late catagen stages, were evaluated relatively to stage P6,
      representing the hair follicle growing phase, to demonstrate dynamics of gene
      activation during the catagen. Several statistically significant alterations were
      observed at P15 and particularly at P17. Bnip3L and caspase-12 identified by the
      PCR arrays at both catagen stages were additionally localized using
      immunofluorescence and were reported in physiological hair development for the
      first time. 

PMID- 25943458
TI  - Comparative Pharmacology of Risperidone and Paliperidone.
AB  - Antipsychotics, risperidone, and risperidone's active metabolite, paliperidone (9
      hydroxyrisperidone), are related molecules used for the treatment of
      schizophrenia and related disorders. Differences in receptor binding, 5-HT2A/D2
      (serotonin/dopamine) binding ratios, and mitochondrial proteomics suggest that
      the effects of risperidone and paliperidone on neuronal firing, regulation of
      mitochondrial function, and movement are different. This review seeks to explore
      the most significant differences at the molecular level between risperidone and
      paliperidone, as reported in preclinical studies. Although risperidone shows
      higher affinity for 5-HT receptors, paliperidone does not fit this profile. Thus,
      the risperidone 5-HT2A/D2 binding ratio is significantly lower than the
      paliperidone 5-HT2A/D2 binding ratio. Paliperidone, similar to lithium and
      valproate, affects expression levels and phosphorylation of complex I and V
      proteins in synaptoneurosomal preparations of rat prefrontal cortex, suggesting
      that paliperidone behaves as a mood stabilizer. It is apparent that the presence
      of a hydroxyl group in the paliperidone molecule confers increased hydrophilicity
      to this drug compared with its parent, risperidone; thus, this contributes to
      differential effects on mitochondrial movement, protein expression, and
      phosphorylation. These differences are reflected in synaptic plasticity and
      neuronal firing and have only recently been implicated in the mechanisms of
      mitochondrial function and movement. 

PMID- 25943460
TI  - High-magnitude mechanical strain inhibits the differentiation of bone-forming rat
      calvarial progenitor cells.
AB  - PURPOSE: Orthodontic tooth movement occurs during the bone remodeling induced by
      therapeutic mechanical strain. It is important to investigate the relation
      between the strength of mechanical stress and bone formation activity. The aim of
      this study was to determine the effect of high-magnitude mechanical strain on
      bone formation in detail. MATERIALS AND METHODS: Osteoblast-like cells isolated
      from fetal rat calvariae were loaded with 18% cyclic tension force (TF) for 48 h.
      To phenotypically investigate the effect of TF, we measured the number and the
      size of bone nodules stained by von Kossa technique on day 21 after cell seeding
      and determined the calcium content of bone nodules on day 14. Furthermore, we
      examined the gene expression of BMP-2, Runx2 and Msx2, which are important
      factors for bone nodule formation, on days 1, 4 and 7 after TF loading. RESULTS:
      The maximum bone nodule size in the control group was 1620 and 719 MUm in the TF
      group. Furthermore, the mean number of bone nodules sized over 360 MUm in the TF
      group was significantly decreased compared to the control group. The calcium
      content was also significantly decreased to 42% by TF loading. The mRNA
      expression of BMP-2, Runx2 and Msx2 was decreased 1 and 4 days after TF loading.
      CONCLUSION: The differentiation of bone forming progenitor cells into bone nodule
      forming cells was inhibited by TF due to the decreased expression of bone
      formation related factors such as BMP-2, Runx2 and Msx2.

PMID- 25943461
TI  - Expression of thrombospondin-1 by tumor cells in patient-derived ovarian
      carcinoma xenografts.
AB  - PURPOSE: Thrombospondin-1 (TSP-1), a major regulator of cell interaction with the
      environment, is often deregulated in cancers, including ovarian carcinoma. Both
      the tumor and the host cells can release TSP-1 in the tumor microenvironment. The
      relative contribution of the two sources in determining TSP-1 levels in ovarian
      cancer remains to be elucidated. This study was designed to investigate the
      expression of tumor TSP-1 in a panel of 29 patient-derived ovarian adenocarcinoma
      xenografts (PDX), using analytical tools specific for human (tumor-derived)
      rather than murine (host-derived) TSP-1. METHODOLOGY: Human-specific microarray
      and ELISA were used to measure tumor TSP-1 expression and plasma levels. RESULTS:
      Tumor-derived TSP-1 was heterogeneously expressed in PDX. Expression was higher
      in the corresponding original patient's tumor, where stroma-derived TSP-1 is also
      analyzed, indicating that both the tumor and the host contribute to TSP-1
      production. TSP-1 was differentially expressed according to tumor grade, but not
      affected by p53 expression or mutational status. Findings were confirmed in an
      external gene expression dataset (101 patients). In a functional enrichment
      analysis, TSP-1 correlated with genes related to angiogenesis, cell motility,
      communication and shape. Plasma TSP-1, detectable in 10/11 PDX, was not
      associated to its expression in the tumor. The possible association of plasma TSP
      1 with p53 mutations and response to chemotherapy warrants further investigation.
      CONCLUSIONS: Ovarian carcinoma PDX are a useful tool to investigate the relative
      contribution of stroma and tumor cells in the production of tumor associated
      factors, in relation to the tumor behavior, molecular properties and response to
      therapy.

PMID- 25943462
TI  - Repair of urethral defects with polylactid acid fibrous membrane seeded with
      adipose-derived stem cells in a rabbit model.
AB  - AIM: The aim of this study is to evaluate the capacity of polylactid acid (PLA)
      fibrous membrane seeded with allogeneic rabbit adipose tissue-derived stem cells
      (ADSCs) to repair urethral defects in a rabbit model. MATERIALS AND METHODS:
      Rabbit ADSCs were harvested and phenotypically characterized. Twenty-four New
      Zealand male rabbits with 5-mm urethral mucosal defects were randomly divided
      into two groups. They underwent urethroplasty either with PLA fibrous membrane
      seeded with ADSCs (group A) or blank PLA fibrous membrane (group B). At 4 and 6
      weeks after urethroplasty, the urethral grafts were collected and analyzed
      grossly and histologically. The incidence rate of urethrostenosis was measured.
      RESULTS: The adipose tissue-derived cells in monolayer culture showed a typical
      morphology of mesenchymal stem cells (MSCs). They were positive for the MSC
      marker CD44 but negative for lineage markers CD45 and CD105. Six weeks after
      surgery, the incidence rate of urethrostenosis in group A was significantly lower
      than that in group B (p < 0.05). In group A, the ADSC-seeded grafts showed a
      normal urethral architecture with a thickened muscle layer. In contrast, the
      newly developed urethra in group B demonstrated a fewer number of urothelial
      layers and scarce or no smooth muscle cells. CONCLUSION: The PLA scaffold seeded
      with ADSCs is effective in urethral regeneration in a rabbit model. ADSCs may
      represent a promising source of seed cells for urethral tissue engineering.

PMID- 25943463
TI  - Reflex anuria: a rare complication of prophylactic ureteral catheterization.

PMID- 25943464
TI  - Co-suturing SURGICEL((r)) and colonic fat to achieve hemostasis in presacral
      hemorrhage.

PMID- 25943465
TI  - Teaching braille letters, numerals, punctuation, and contractions to sighted
      individuals.
AB  - Braille-character recognition is one of the foundational skills required for
      teachers of braille. Prior research has evaluated computer programming for
      teaching braille-to-print letter relations (e.g., Scheithauer & Tiger, 2012). In
      the current study, we developed a program (the Visual Braille Trainer) to teach
      not only letters but also numerals, punctuation, symbols, and contractions; we
      evaluated this program with 4 sighted undergraduate participants. Exposure to
      this program resulted in mastery of all braille-to-print relations for each
      participant. 

PMID- 25943466
TI  - Beat-to-beat, ambulatory hour-to-hour, and home day-to-day variabilities in blood
      pressure, pulse pressure, and heart rate in comparison with each other and with
      target-organ damage.
AB  - OBJECTIVE: The objective was to compare beat-to-beat, ambulatory hour-to-hour,
      and home day-to-day variability in blood pressure (BP), pulse pressure (PP), and
      heart rate (HR) with each other and with target-organ damage. METHODS: We studied
      a population-based sample of Finnish adults including 150 healthy participants
      aged between 35 and 64 years. Variability in BP and HR was assessed using self
      measured morning and evening recordings from seven consecutive days and 24-h
      ambulatory recordings. Frequency domain measures of beat-to-beat BP variability
      and baroreflex sensitivity were determined from 5-min time series. The study
      participants underwent clinical examination, a clinical interview, measurement of
      urine albumin levels, and echocardiographic examination. RESULTS: Home BP/PP
      variability parameters and low frequency (LF) power of beat-to-beat BP/PP
      variability were mainly associated with left ventricular mass index (LVMI) in
      models adjusted for age, sex, and BP/PP level. The associations of LVMI with PP
      variability parameters were stronger than the corresponding associations with BP
      parameters. The associations of PP variability parameters with LVMI were stronger
      in old than in young individuals. Home BP/PP variability parameters were mainly
      associated with the LF power of beat-to-beat BP/PP variability in models adjusted
      for age, sex, and beat-to-beat BP/PP level and the associations were stronger in
      old than in young individuals. Home HR variability parameters and 24-h hour-to
      hour HR variability were mainly associated with LF/high-frequency powers of beat
      to-beat HR variability. CONCLUSION: Reading-to-reading BP/PP variability
      parameters and their corresponding beat-to-beat variability parameters are
      partially connected, possibly to common regulatory mechanisms. Their prognostic
      significance in relation to cardiovascular outcome needs further investigation.

PMID- 25943467
TI  - Blood pressure measurement reliability among different racial-ethnic groups in a
      stroke prevention study: methodological issues to avoid misinterpretation.

PMID- 25943468
TI  - Response: Blood pressure measurement reliability among different racial-ethnic
      groups in a stroke prevention study: methodological issues that strengthen our
      results.

PMID- 25943469
TI  - How to reform western care payment systems according to physicians, policy
      makers, healthcare executives and researchers: a discrete choice experiment.
AB  - BACKGROUND: Many developed countries are reforming healthcare payment systems in
      order to limit costs and improve clinical outcomes. Knowledge on how different
      groups of professional stakeholders trade off the merits and downsides of
      healthcare payment systems is limited. METHODS: Using a discrete choice
      experiment we asked a sample of physicians, policy makers, healthcare executives
      and researchers from Canada, Europe, Oceania, and the United States to choose
      between profiles of hypothetical outcomes on eleven healthcare performance
      objectives which may arise from a healthcare payment system reform. We used a
      Bayesian D-optimal design with partial profiles, which enables studying a large
      number of attributes, i.e. the eleven performance objectives, in the experiment.
      RESULTS: Our findings suggest that (a) moving from current payment systems to a
      value-based system is supported by physicians, despite an income trade-off, if
      effectiveness and long term cost containment improve. (b) Physicians would gain
      in terms of overall objective fulfillment in Eastern Europe and the US, but not
      in Canada, Oceania and Western Europe. Finally, (c) such payment reform more
      closely aligns the overall fulfillment of objectives between stakeholders such as
      physicians versus healthcare executives. CONCLUSIONS: Although the findings
      should be interpreted with caution due to the potential selection effects of
      participants, it seems that the value driven nature of newly proposed and/or
      introduced care payment reforms is more closely aligned with what stakeholders
      favor in some health systems, but not in others. Future studies, including the
      use of random samples, should examine the contextual factors that explain such
      differences in values and buy-in. JEL CLASSIFICATION: C90, C99, E61, I11, I18,
      O57.

PMID- 25943470
TI  - Lack of physical activity in Hispanic adults.

PMID- 25943471
TI  - The SwissLipids knowledgebase for lipid biology.
AB  - MOTIVATION: Lipids are a large and diverse group of biological molecules with
      roles in membrane formation, energy storage and signaling. Cellular lipidomes may
      contain tens of thousands of structures, a staggering degree of complexity whose
      significance is not yet fully understood. High-throughput mass spectrometry-based
      platforms provide a means to study this complexity, but the interpretation of
      lipidomic data and its integration with prior knowledge of lipid biology suffers
      from a lack of appropriate tools to manage the data and extract knowledge from
      it. RESULTS: To facilitate the description and exploration of lipidomic data and
      its integration with prior biological knowledge, we have developed a knowledge
      resource for lipids and their biology-SwissLipids. SwissLipids provides curated
      knowledge of lipid structures and metabolism which is used to generate an in
      silico library of feasible lipid structures. These are arranged in a hierarchical
      classification that links mass spectrometry analytical outputs to all possible
      lipid structures, metabolic reactions and enzymes. SwissLipids provides a
      reference namespace for lipidomic data publication, data exploration and
      hypothesis generation. The current version of SwissLipids includes over 244 000
      known and theoretically possible lipid structures, over 800 proteins, and curated
      links to published knowledge from over 620 peer-reviewed publications. We are
      continually updating the SwissLipids hierarchy with new lipid categories and new
      expert curated knowledge. AVAILABILITY: SwissLipids is freely available at
      http://www.swisslipids.org/. CONTACT: alan.bridge@isb-sib.ch SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 25943472
TI  - Automated band annotation for RNA structure probing experiments with numerous
      capillary electrophoresis profiles.
AB  - MOTIVATION: Capillary electrophoresis (CE) is a powerful approach for structural
      analysis of nucleic acids, with recent high-throughput variants enabling three
      dimensional RNA modeling and the discovery of new rules for RNA structure design.
      Among the steps composing CE analysis, the process of finding each band in an
      electrophoretic trace and mapping it to a position in the nucleic acid sequence
      has required significant manual inspection and remains the most time-consuming
      and error-prone step. The few available tools seeking to automate this band
      annotation have achieved limited accuracy and have not taken advantage of
      information across dozens of profiles routinely acquired in high-throughput
      measurements. RESULTS: We present a dynamic-programming-based approach to
      automate band annotation for high-throughput capillary electrophoresis. The
      approach is uniquely able to define and optimize a robust target function that
      takes into account multiple CE profiles (sequencing ladders, different chemical
      probes, different mutants) collected for the RNA. Over a large benchmark of multi
      profile datasets for biological RNAs and designed RNAs from the EteRNA project,
      the method outperforms prior tools (QuSHAPE and FAST) significantly in terms of
      accuracy compared with gold-standard manual annotations. The amount of
      computation required is reasonable at a few seconds per dataset. We also
      introduce an 'E-score' metric to automatically assess the reliability of the band
      annotation and show it to be practically useful in flagging uncertainties in band
      annotation for further inspection. AVAILABILITY AND IMPLEMENTATION: The
      implementation of the proposed algorithm is included in the HiTRACE software,
      freely available as an online server and for download at
      http://hitrace.stanford.edu. CONTACT: sryoon@snu.ac.kr or rhiju@stanford.edu
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 25943473
TI  - Fracture diagnostics, unnecessary travel and treatment: a comparative study
      before and after the introduction of teleradiology in a remote general practice.
AB  - BACKGROUND: Teleradiology entails attainment of x-rays in one location, transfer
      over some distance and assessment at another location for diagnosis or
      consultation. This study documents fracture diagnostics, unnecessary trips to the
      hospital, treatment and number of x-rays for the years 2006 and 2009, before and
      after the introduction of teleradiology in a general practice on the island of
      Ameland in the north of the Netherlands. METHODS: In a retrospective,
      descriptive, observational before and after study of the introduction of x-ray
      facilities in an island-based general practice, we compared the number of
      accurately diagnosed fractures, unnecessary trips, treatments and number of x
      rays taken in 2006 when only a hospital x-ray facility was available 5 hours away
      with those in 2009 after an x-ray facility became available at a local general
      practice. All patients visiting a general practice on the island of Ameland in
      2006 and 2009 with trauma and clinical suspicion of a fracture, dislocation or
      sprain were included in the study. The initial clinical diagnoses, including
      those based on the outcomes of x-rays, were compared for the two years and also
      whether the patients were treated at home or in hospital. RESULTS: A total of 316
      and 490 patients with trauma visited a general practice in 2006 and 2009,
      respectively. Of these patients, 66 and 116 were found to have fractures or
      dislocations in the two years, respectively. In 2006, 83 x-rays were ordered; in
      2009, this was 284. In 2006, 9 fractures were missed; in 2009, this was only 2.
      In 2006, 15 patients with fractures or dislocations were treated at the general
      practice; in 2009, this had increased to 77. CONCLUSION: Since the introduction
      of teleradiology the number of missed fractures in patients visiting the general
      practice with trauma and the number of the unnecessary trips to a hospital are
      reduced. In addition more patients with fractures and dislocations can be treated
      in the general practice as opposed to the hospital.

PMID- 25943474
TI  - A shared language regarding sedation and delirium in critically ill patients.
AB  - BACKGROUND: Patients in intensive care units who develop delirium, experience
      longer stay in intensive care as well as increased morbidity and mortality. A
      questionnaire in 2009 showed that there was no consensus in Denmark regarding the
      tools to be used to assess sedation or delirium, the patient groups they should
      be used in, or the frequency of assessment. AIMS: The aims of this survey were to
      describe clinical practice regarding the assessment of sedation and delirium in
      intensive care patients and to compare the results with those obtained in 2009.
      METHOD: A questionnaire was sent via e-mail to all intensive care units in
      Denmark caring for ventilated adult patients. An intensive care nurse with daily
      patient contact was asked to answer questions about the unit's practice regarding
      the tools used to assess sedation and delirium in adult patients. RESULTS: In
      all, 98% of the intensive care units responded. Richmond Agitation-Sedation Scale
      was the most used tool for sedation assessment, and Confusion Assessment Method
      for the Intensive Care Unit was used only for delirium assessment. CONCLUSION: A
      shared language for sedation and delirium assessment was identified as essential
      in supporting care delivery. RELEVANCE TO CLINICAL PRACTICE: A systematic use of
      a shared language according to sedation and delirium in intensive care units can
      minimize mistakes in transfer of patients and minimize the risk of doubly
      traumatising patients.

PMID- 25943475
TI  - Enhanced fitness and renal function in Type 2 diabetes.
AB  - AIMS: To investigate the renal effects of fitness in people with diabetes with
      mild renal dysfunction. METHODS: The effect of a 12-week exercise programme on
      estimated GFR in 128 people with diabetes was evaluated. RESULTS: All
      cardiometabolic variables improved after 12 weeks of supervised exercise.
      Although there was a modest 3.9% increase in estimated GFR from baseline in the
      128 people who completed the study, those with baseline chronic kidney disease
      stages 2 and 3 were found to have significant (6 and 12%, respectively; p < 0.01)
      improvements in post-exercise estimated GFR. Moreover, 42% of the people with
      chronic kidney disease stage 3 improved to chronic kidney disease stage 2 after
      the intervention. CONCLUSION: Short-term exercise improves renal function in
      those with more moderate baseline chronic kidney disease. Thus, renal function
      appears to be responsive to enhanced physical fitness. Being a strong and
      modifiable risk factor, enhanced fitness should be considered a non
      pharmacological adjunct in the management of diabetic kidney disease.

PMID- 25943476
TI  - Early prenatal exposure to LPS results in anxiety- and depression-related
      behaviors in adulthood.
AB  - Maternal immune activation can result in different behavioral abnormalities and
      brain dysfunction, depending on the nature of the inflammogen and the timing of
      the challenge. Few studies report the possible link between prenatal exposure to
      inflammation and mood disorders. Here we aimed to evaluate the effects of a
      single low lipopolysaccharide (LPS) injection to the dam at gestational day 9 on
      the offspring behavior and hippocampal function. We found that mice exposed to
      LPS show anxiety- and depression-related behaviors. Specifically, we found that
      animals prenatally exposed to LPS avoided the open arms of an elevated plus maze,
      the center of an open field and the lit side of a light/dark box, and they spent
      more time immobile in both the forced swimming and tail suspension tests, when
      compared with offspring of saline-injected dams. In addition, LPS mice had
      reduced serotonin and noradrenaline levels in the hippocampus and diminished
      Reelin immunoreactivity in the dentate gyrus, while their adult hippocampal
      neurogenesis was not affected. Results presented here support specific long-term
      effects of the response to a bacterial immunogen early in pregnancy, as opposed
      to different effects previously reported of viral immunogens and/or responses in
      late pregnancy. Our work adds to recent reports and stresses the relevance of
      considering prenatal exposure to a maternal immune response as a risk factor for
      mood disorders. 

PMID- 25943477
TI  - Developmental expression of vascular endothelial growth factor receptor 3 and
      vascular endothelial growth factor C in forebrain.
AB  - Increased understanding of the neurovascular niche suggests that development of
      the central nervous system (CNS) and its vasculature is coordinated through
      shared regulatory factors. These include the vascular endothelial growth factor
      (VEGF) family, reported to promote neuroproliferation and neuroprotection in
      addition to angiogenesis via its receptors VEGFR1-3. VEGFR3, a mediator of
      lymphangiogenesis, is expressed in murine and rat brain from early gestation, has
      been associated with neural progenitors and neurons (Choi et al., 2010) and
      oligodendroglia (Le Bras et al., 2006) in the developing cortex and is reported
      to mediate adult neurogenesis in the subventricular zone (SVZ) (Calvo et al.,
      2011). The early expression pattern of VEGFR3 protein and its cellular
      associations has not as yet been comprehensively reported. We describe the
      temporal expression of VEGFR3 protein at a cellular level and its close
      association with its VEGFC ligand, determined by double-labeling
      immunohistochemistry in the developing rat brain from embryonic day (E) 13 to
      postnatal day (P) 23. We found high expression of VEGFR3 in the ventricular zone
      and along radial glia in early gestation in association with neural stem cells
      and neuroblasts. Similar expression patterns were seen in the immature olfactory
      bulb and optic cup. In later development we found less expression by neural
      progenitors in proliferative regions including the SVZ and dentate gyrus of the
      hippocampus. In contrast, VEGFR3 expression increased with development in the
      cortex in neurons and astrocytes, and appeared in the emerging population of
      oligodendroglial progenitors. High expression in ventricular ependyma, choroid
      plexus and pigmented retinal epithelium was noted from E18. VEGFC ligand was
      found in association with VEGFR3 throughout development, with highest expression
      in embryonic stages. Our findings suggest an important role for VEGFC/VEGFR3
      signaling in neuronal proliferation in early forebrain development, and ongoing
      functions with niche neurogenesis, glial and ependymal function in the maturing
      postnatal brain. 

PMID- 25943478
TI  - Gray matter correlates of migraine and gender effect: A meta-analysis of voxel
      based morphometry studies.
AB  - BACKGROUND: An increasing number of neuroimaging studies have revealed gray
      matter (GM) anomalies of several brain regions by voxel-based morphometry (VBM)
      studies in migraineurs. However, not all the studies reported entirely consistent
      findings. Our aim is to investigate concurrence across VBM studies to help
      clarify the structural anomalies underpinning this condition. METHODS: A
      systematic search of VBM studies of patients with migraine and healthy controls
      (HC) published in PubMed and Embase databases from January 2000 to March 2014 was
      conducted. A quantitative meta-analysis of whole-brain VBM studies in patients
      with migraine compared with HC was performed by means of anisotropic effect size
      version of signed differential mapping (AES-SDM) software package. RESULTS: Nine
      studies comprising 222 patients with migraine and 230 HC subjects were included
      in the present study. Compared to HC subjects, the patients group showed
      consistent decreased GM in the posterior insular-opercular regions, the
      prefrontal cortex, and the anterior cingulate cortex. Results remained largely
      unchanged in the following jackknife sensitivity analyses. Meta-regression
      analysis showed that a higher percentage of females in the patient sample was
      associated with decreased GM in the right dorsolateral prefrontal cortex.
      CONCLUSIONS: This is the first quantitative whole-brain VBM meta-analysis in
      migraine showing strong evidence of brain GM anomalies within the pain-processing
      neural network. Further longitudinal investigations are needed to determine
      whether these structural anomalies are reversible with effective treatment on
      migraine.

PMID- 25943479
TI  - GABAergic inhibition shapes SAM responses in rat auditory thalamus.
AB  - Auditory thalamus (medial geniculate body [MGB]) receives ascending inhibitory
      GABAergic inputs from inferior colliculus (IC) and descending GABAergic
      projections from the thalamic reticular nucleus (TRN) with both inputs postulated
      to play a role in shaping temporal responses. Previous studies suggested that
      enhanced processing of temporally rich stimuli occurs at the level of MGB, with
      our recent study demonstrating enhanced GABA sensitivity in MGB compared to IC.
      The present study used sinusoidal amplitude-modulated (SAM) stimuli to generate
      modulation transfer functions (MTFs), to examine the role of GABAergic inhibition
      in shaping the response properties of MGB single units in anesthetized rats. Rate
      MTFs (rMTFs) were parsed into "bandpass (BP)", "mixed (Mixed)", "highpass (HP)"
      or "atypical" response types, with most units showing the Mixed response type.
      GABAA receptor blockade with iontophoretic application of the GABAA receptor
      (GABAAR) antagonist gabazine (GBZ) selectively altered the response properties of
      most MGB neurons examined. Mixed and HP units showed significant GABAAR-mediated
      SAM-evoked rate response changes at higher modulation frequencies (fms), which
      were also altered by N-methyl-d-aspartic acid (NMDA) receptor blockade (2R)-amino
      5-phosphonopentanoate (AP5). BP units, and the lower arm of Mixed units responded
      to GABAAR blockade with increased responses to SAM stimuli at or near the rate
      best modulation frequency (rBMF). The ability of GABA circuits to shape responses
      at higher modulation frequencies is an emergent property of MGB units, not
      observed at lower levels of the auditory pathway and may reflect activation of
      MGB NMDA receptors (Rabang and Bartlett, 2011; Rabang et al., 2012). Together,
      GABAARs exert selective rate control over selected fms, generally without
      changing the units' response type. These results showed that coding of modulated
      stimuli at the level of auditory thalamus is at least, in part, strongly
      controlled by GABA neurotransmission, in delicate balance with glutamatergic
      neurotransmission. 

PMID- 25943480
TI  - Stimulation of alpha1-adrenoceptors facilitates GABAergic transmission onto
      pyramidal neurons in the medial prefrontal cortex.
AB  - Whereas activation of alpha1-adrenoceptors (alpha1-ARs) modulates glutamatergic
      transmission, the roles of alpha1-ARs in GABAergic transmission in the medial
      prefrontal cortex (mPFC) are elusive. Here, we examined the effects of the alpha1
      AR agonist phenylephrine (Phe) on GABAergic transmission onto pyramidal neurons
      in the deep layers of the mPFC. We found that bath application of Phe dose
      dependently increased the amplitude of evoked IPSCs (eIPSCs). Phe increased the
      frequency but not the amplitude of miniature IPSCs (mIPSCs). Ca(2+) influx
      through T-type voltage-gated calcium channels is required for Phe-induced
      increases in GABA release. Phe increases GABA release probability and the number
      of releasable vesicles. Phe depolarizes the fast-spiking (FS) interneurons
      without effects on the firing rate of action potentials (APs) of interneurons.
      Phe-induced depolarization is independent of extracellular Na(+), Ca(2+) and T
      type calcium channels, but requires inward rectifier K(+) channels (Kirs). The
      present study demonstrates that Phe enhances GABAergic transmission onto mPFC
      pyramidal neurons through inhibiting interneurons Kirs, which further depolarizes
      interneurons leading to increase in Ca(2+) influx via T-type calcium channels.
      Our results may provide a cellular and molecular mechanism that helps explain
      alpha1-AR-induced PFC dysfunction.

PMID- 25943481
TI  - Intervention with exercise restores motor deficits but not nigrostriatal loss in
      a progressive MPTP mouse model of Parkinson's disease.
AB  - Many studies have investigated exercise therapy in Parkinson's disease (PD) and
      have shown benefits in improving motor deficits. However, exercise does not slow
      down the progression of the disease or induce the revival of lost nigrostriatal
      neurons. To examine the dichotomy of behavioral improvement without the slowing
      or recovery of dopaminergic cell or terminal loss, we tested exercise therapy in
      an intervention paradigm where voluntary running wheels were installed half-way
      through our progressive PD mouse model. In our model, 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) is administered over 4 weeks with increased doses each
      week (8, 16, 24, 32-kg/mg). We found that after 4 weeks of MPTP treatment, mice
      that volunteered to exercise had behavioral recovery in several measures despite
      the loss of 73% and 53% tyrosine hydroxylase (TH) within the dorsolateral (DL)
      striatum and the substantia nigra (SN), respectively which was equivalent to the
      loss seen in the mice that did not exercise but were also administered MPTP for 4
      weeks. Mice treated with 4 weeks of MPTP showed a 41% loss of vesicular monoamine
      transporter II (VMAT2), a 71% increase in the ratio of glycosylated/non
      glycosylated dopamine transporter (DAT), and significant increases in glutamate
      transporters including VGLUT1, GLT-1, and excitatory amino acid carrier 1. MPTP
      mice that exercised showed recovery of all these biomarkers back to the levels
      seen in the vehicle group and showed less inflammation compared to the mice
      treated with MPTP for 4 weeks. Even though we did not measure tissue dopamine
      (DA) concentration, our data suggest that exercise does not alleviate motor
      deficits by sparing nigrostriatal neurons, but perhaps by stabilizing the
      extraneuronal neurotransmitters, as evident by a recovery of DA and glutamate
      transporters. However, suppressing inflammation could be another mechanism of
      this locomotor recovery. Although exercise will not be a successful treatment
      alone, it could supplement other pharmaceutical approaches to PD therapy.

PMID- 25943482
TI  - Auditory cortex involvement in emotional learning and memory.
AB  - Emotional memories represent the core of human and animal life and drive future
      choices and behaviors. Early research involving brain lesion studies in animals
      lead to the idea that the auditory cortex participates in emotional learning by
      processing the sensory features of auditory stimuli paired with emotional
      consequences and by transmitting this information to the amygdala. Nevertheless,
      electrophysiological and imaging studies revealed that, following emotional
      experiences, the auditory cortex undergoes learning-induced changes that are
      highly specific, associative and long lasting. These studies suggested that the
      role played by the auditory cortex goes beyond stimulus elaboration and
      transmission. Here, we discuss three major perspectives created by these data. In
      particular, we analyze the possible roles of the auditory cortex in emotional
      learning, we examine the recruitment of the auditory cortex during early and late
      memory trace encoding, and finally we consider the functional interplay between
      the auditory cortex and subcortical nuclei, such as the amygdala, that process
      affective information. We conclude that, starting from the early phase of memory
      encoding, the auditory cortex has a more prominent role in emotional learning,
      through its connections with subcortical nuclei, than is typically acknowledged. 

PMID- 25943483
TI  - Cardiac over-expression of microRNA-1 induces impairment of cognition in mice.
AB  - Large cohort studies have revealed a close relationship between cognitive
      impairment and cardiovascular diseases, although the mechanism underlying this
      relationship remains incompletely understood. In this study, using a transgenic
      (Tg) mouse model of cardiac-specific over-expression of microRNA-1-2 (miR-1-2),
      we observed that microRNA-1 (miR-1) levels were increased not only in the heart
      but also in the hippocampus and blood, whereas its levels did not change in the
      skeletal muscle of Tg mice compared with age-matched wild-type (WT) mice. Six
      month-old Tg mice showed cognitive impairment compared with age-matched WT mice,
      as assessed using the Morris Water Maze test. The brain-derived neurotrophic
      factor (BDNF) level and cyclic AMP-responsive element-binding protein (CREB)
      phosphorylation were also significantly reduced in the hippocampi of the Tg mice,
      as evaluated by Western blot. Further examination showed that BDNF protein
      expression was down- or up-regulated by miR-1 over-expression or inhibition,
      respectively, and was unchanged by binding site mutations or miRNA-masks for the
      3'UTR of Bdnf, indicating that this gene is a potential target of miR-1.
      Knockdown of miR-1 by hippocampal stereotaxic injection of an anti-miR-1
      oligonucleotide fragment carried by a lentivirus vector (lenti-pre-AMO-miR-1) led
      to up-regulation of BDNF expression and prevented the reduction in cognitive
      performance in the Tg mice without affecting cardiac function. Our findings
      demonstrate that cardiac over-expression of miR-1 also induces behavioral
      abnormalities that may be associated, at least in part, with the down-regulation
      of BDNF expression in the hippocampus. This study definitely contributes to the
      understanding of the relationship between cardiovascular disease and cognitive
      impairment. 

PMID- 25943484
TI  - Involvement of dopaminergic and cholinergic systems in social isolation-induced
      deficits in social affiliation and conditional fear memory in mice.
AB  - Post-weaning social isolation rearing (SI) in rodents elicits various behavioral
      abnormalities including attention deficit hyperactivity disorder-like behaviors.
      In order to obtain a better understanding of SI-induced behavioral abnormalities,
      we herein investigated the effects of SI on social affiliation and conditioned
      fear memory as well as the neuronal mechanism(s) underlying these effects. Four
      week-old male mice were group-housed (GH) or socially isolated for 2-4 weeks
      before the experiments. The social affiliation test and fear memory conditioning
      were conducted at the age of 6 and 7 weeks, respectively. SI mice were
      systemically administered saline or test drugs 30 min before the social
      affiliation test and fear memory conditioning. Contextual and auditory fear
      memories were elucidated 1 and 4 days after fear conditioning. Social affiliation
      and contextual and auditory fear memories were weaker in SI mice than in GH mice.
      Methylphenidate (MPH), an inhibitor for dopamine transporters, ameliorated the SI
      induced social affiliation deficit and the effect was attenuated by SCH23390, a
      D1 receptor antagonist, but not by sulpiride, a D2 receptor antagonist. On the
      other hand, tacrine, an acetylcholinesterase inhibitor, had no effect on this
      deficit. In contrast, tacrine improved SI-induced deficits in fear memories in a
      manner that was reversed by the muscarinic receptor antagonist scopolamine, while
      MPH had no effect on memory deficits. Neurochemical studies revealed that SI down
      regulated the expression levels of the phosphorylated forms of neuro-signaling
      proteins, calmodulin-dependent kinase II (p-CaMKII), and cyclic AMP-responsive
      element binding protein (p-CREB), as well as early growth response protein-1 (Egr
      1) in the hippocampus. The administration of MPH or tacrine before fear
      conditioning had no effect on the levels of the phosphorylated forms of the neuro
      signaling proteins elucidated following completion of the auditory fear memory
      test; however, when analyzed 30 min after the administration of the test drugs,
      tacrine significantly attenuated the SI-induced decrease in p-CaMKII, p-CREB, and
      Egr-1 in a manner reversible by scopolamine. Our results suggest that SI-induced
      deficits in social affiliation and conditioned fear memory were mediated by
      functional alterations to central dopaminergic and cholinergic systems,
      respectively.

PMID- 25943485
TI  - Lipoxin A4 attenuates radicular pain possibly by inhibiting spinal ERK, JNK and
      NF-kappaB/p65 and cytokine signals, but not p38, in a rat model of non
      compressive lumbar disc herniation.
AB  - Inflammatory response induced by protrused nucleus pulposus (NP) has been shown
      to play a crucial role in the process of radicular pain. Lipoxins represent a
      unique class of lipid mediators that have anti-inflammatory and pro-resolving
      action. The present study was undertaken to investigate if intrathecal lipoxin A4
      (LXA4) could alleviate mechanical allodynia in the rat models of application of
      NP to the L5 dorsal root ganglion (DRG). Non-compressive models of application of
      NP to L5 DRG were established and intrathecal catheterization for drug
      administration was performed in rats. Daily intrathecal injection of vehicle or
      LXA4 (10ng or 100ng) was performed for three successive days post-operation.
      Mechanical thresholds were tested and the ipsilateral lumbar (L4-L6) segment of
      spinal dorsal horns were removed for the determination of tumor necrosis factor
      alpha (TNF-alpha), IL-1beta, transforming growth factor-beta1 (TGF-beta1) and IL
      10 expression and NF-kappaB/p65, extracellular signal-regulated kinase (ERK), C
      Jun N-terminal kinase (JNK) and P38 expression. Application of NP to DRG in rats
      induced mechanical allodynia, increased the expression of pro-inflammatory
      factors (TNF-alpha and IL-1beta), NF-kappaB/p65, the phosphorylated-ERK (p-ERK), 
      JNK (p-JNK) and -P38 (p-p38) and decreased the expression of anti-inflammatory
      cytokines (TGF-beta1 and IL-10) in the ipsilateral lumbar (L4-L6) segment of
      spinal dorsal horns. Intrathecal injection of LXA4 alleviated the development of
      neuropathic pain, inhibited the upregulation of pro-inflammatory cytokines (TNF
      alpha and IL-1beta), upregulated the expression of anti-inflammatory cytokines
      (TGF-beta1 and IL-10) and attenuated the activation of NF-kappaB/p65, p-ERK, p
      JNK, but not p-p38, in a dose-dependent manner. In this study, we have
      demonstrated that LXA4 potently alleviate radicular pain in a rat model of non
      compressive lumbar disc herniation. The anti-inflammatory and pro-resolution
      properties of LXA4 have shown a great promise for the management of radicular
      pain caused by intervertebral disc herniation.

PMID- 25943486
TI  - Nutraceutical properties of the methanolic extract of edible mushroom
      Cantharellus cibarius (Fries): primary mechanisms.
AB  - The methanolic extract of the wild edible mushroom Cantharellus cibarius Fr.
      (chanterelle) was analyzed for in vitro antioxidative, cytotoxic,
      antihypertensive and antibacterial activities. Various primary and secondary
      metabolites were found. Phenols were the major antioxidant components found in
      the extract (49.8 mg g(-1)), followed by flavonoids, whose content was
      approximately 86% of the total phenol content. Antioxidant activity, measured by
      four different methods, was high for inhibition of lipid peroxidation (EC50 =
      1.21 mg mL(-1)) and chelating ability (EC50 = 0.64 mg mL(-1)). The antioxidant
      activity of the C. cibarius methanol extract was achieved through chelating iron
      compared to hydrogen atom and/or electron transfer. The extract showed good
      selectivity in cytotoxicity on human cervix adenocarcinoma HeLa, breast carcinoma
      MDA-MB-453 and human myelogenous leukemia K562, compared to normal control human
      fetal lung fibroblasts MRC-5 and human lung bronchial epithelial cells BEAS-2B.
      The extract had inhibitory activity against angiotensin converting I enzyme (ACE)
      (IC50 = 0.063 mg mL(-1)). The extract revealed selective antimicrobial activity
      against Gram-positive bacteria with the highest potential against E. faecalis.
      The medicinal and health benefits, observed in wild C. cibarius mushroom, seem an
      additional reason for its traditional use as a popular delicacy food.

PMID- 25943487
TI  - Unexpected cryptic species diversity in the widespread coral Seriatopora hystrix
      masks spatial-genetic patterns of connectivity.
AB  - Mounting evidence of cryptic species in a wide range of taxa highlights the need
      for careful analyses of population genetic data sets to unravel within-species
      diversity from potential interspecies relationships. Here, we use microsatellite
      loci and hierarchical clustering analysis to investigate cryptic diversity in
      sympatric and allopatric (separated by 450 km) populations of the widespread
      coral Seriatopora hystrix on the Great Barrier Reef. Structure analyses delimited
      unique genetic clusters that were confirmed by phylogenetic and extensive
      population-level analyses. Each of four sympatric yet distinct genetic clusters
      detected within S. hystrix demonstrated greater genetic cohesion across regional
      scales than between genetic clusters within regions (<10 km). Moreover, the
      magnitude of genetic differentiation between different clusters (>0.620 G"ST )
      was similar to the difference between S. hystrix clusters and the congener S.
      caliendrum (mean G"ST 0.720). Multiple lines of evidence, including differences
      in habitat specificity, mitochondrial identity, Symbiodinium associations and
      morphology, corroborate the nuclear genetic evidence that these distinct clusters
      constitute different species. Hierarchical clustering analysis combined with more
      traditional population genetic methods provides a powerful approach for
      delimiting species and should be regularly applied to ensure that ecological and
      evolutionary patterns interpreted for single species are not confounded by the
      presence of cryptic species.

PMID- 25943488
TI  - Chronic arsenic toxicity in sheep of Kurdistan province, western Iran.
AB  - After the detection of arsenic (As) toxicity in sheep from Ebrahim-abad and
      Babanazar villages in Kurdistan province, the concentration of this element in
      drinking water, cultivated soil, alfalfa hay, wool, and blood samples was
      evaluated. Total As concentrations ranged from 119 to 310 MUg/L in drinking
      water, 46.70-819.20 mg/kg in soil 1.90-6.90 mg/kg in vegetation 1.56-10.79 mg/kg
      in sheep's wool, and 86.30-656 MUg/L in blood samples. These very high As
      contents, in all parts of the biogeochemical cycle, exceed the recommended normal
      range for this element compared with a control area. Results indicate that As has
      moved through all compartments of the biogeochemical cycle by way of direct or
      indirect pathways. The present investigation illustrated decreased packed cell
      volume and hemoglobin in sheep from the As-contaminated zone. It was concluded
      that sheep from the contaminated areas suffer from anemia. Chronic As exposure of
      the liver was determined by liver function tests. For this purpose, blood
      aspartate transaminase (AST) and alanine transaminase (ALT) were measured. The
      results show that serum ALT and AST activities are increased significantly (p <
      0.01) in the sheep population exposed to As in the contaminated zone. Moreover,
      chronic As exposure causes injury to hepatocytes and damages the liver.

PMID- 25943489
TI  - Genomic landscape of rat strain and substrain variation.
AB  - BACKGROUND: Since the completion of the rat reference genome in 2003, whole
      genome sequencing data from more than 40 rat strains have become available. These
      data represent the broad range of strains that are used in rat research including
      commonly used substrains. Currently, this wealth of information cannot be used to
      its full extent, because the variety of different variant calling algorithms
      employed by different groups impairs comparison between strains. In addition, all
      rat whole genome sequencing studies to date used an outdated reference genome for
      analysis (RGSC3.4 released in 2004). RESULTS: Here we present a comprehensive,
      multi-sample and uniformly called set of genetic variants in 40 rat strains,
      including 19 substrains. We reanalyzed all primary data using a recent version of
      the rat reference assembly (RGSC5.0 released in 2012) and identified over 12
      million genomic variants (SNVs, indels and structural variants) among the 40
      strains. 28,318 SNVs are specific to individual substrains, which may be
      explained by introgression from other unsequenced strains and ongoing evolution
      by genetic drift. Substrain SNVs may have a larger predicted functional impact
      compared to older shared SNVs. CONCLUSIONS: In summary we present a comprehensive
      catalog of uniformly analyzed genetic variants among 40 widely used rat inbred
      strains based on the RGSC5.0 assembly. This represents a valuable resource, which
      will facilitate rat functional genomic research. In line with previous
      observations, our genome-wide analyses do not show evidence for contribution of
      multiple ancestral founder rat subspecies to the currently used rat inbred
      strains, as is the case for mouse. In addition, we find that the degree of
      substrain variation is highly variable between strains, which is of importance
      for the correct interpretation of experimental data from different labs.

PMID- 25943491
TI  - The ups and downs of clinical translation of new technologies: deja vu all over
      again.

PMID- 25943490
TI  - Placebo-controlled dietary intervention of stress-induced neurovegetative
      disorders with a specific amino acid composition: a pilot-study.
AB  - BACKGROUND: Psychosocial stress leads to altered neuroendocrine functions, such
      as serotonergic dysfunction, as well as alterations of the autonomic nervous
      system and the hypothalamic-pituitary-adrenal (HPA)-axis activity resulting in an
      imbalance between inhibitory and excitatory neurotransmitters. Poor dietary
      intake of L-tryptophan as a precursor of serotonin increases sensitivity to
      stress. METHODS: This randomized, double-blind, placebo-controlled study
      investigated the effect of a specific amino acid composition with micronutrients
      on neurovegetative disorders and the cardiometabolic risk profile in
      psychosocially stressed patients. 32 patients (18-65 years) were eligible for
      protocol analysis. Points in the Psychological Neurological Questionnaire (PNF),
      clinical and blood parameter, in particular the serotonin level, salivary
      cortisol levels, and dietary intake were evaluated at baseline and 12 weeks after
      supplementation. RESULTS: The intervention in the form of either verum or placebo
      resulted in both groups in a significant decrease of neurovegetative symptoms.
      However, patients of the placebo group achieved significantly less points in the
      PNF compared to the verum group. But the rate of responders (>=10 points loss in
      PNF) was not significantly different between the groups. The macronutrient intake
      did not differ between verum and placebo group. On average, the HPA-axis was not
      disturbed in both groups. Blood serotonin indicated in both groups no significant
      correlation with dietary tryptophan intake or PNF. CONCLUSIONS: Daily
      supplementation of a specific amino acid composition with micronutrients in
      psychologically stressed patients resulted in no improvement of neurovegetative
      disorders as measured by the PNF when compared to the placebo group. TRIAL
      REGISTRATION: Clinical Trials.gov ( NCT01425983 ).

PMID- 25943495
TI  - AAV's Golden Jubilee.

PMID- 25943494
TI  - Genome editing technologies: defining a path to clinic.

PMID- 25943496
TI  - Moving forward toward a cure for hemophilia B.

PMID- 25943497
TI  - In utero exposure to methotrexate and risk of congenital malformations.

PMID- 25943498
TI  - [Ketamine as anesthetic agent in electroconvulsion therapy].
AB  - BACKGROUND: Electroconvulsive therapy (ECT) is a well-established, safe and
      effective treatment for severe psychiatric disorders. Ketamine is known as a core
      medication in anesthesiology and has recently gained interest in ECT practice as
      there are three potential advantages: (1) ketamine has no anticonvulsive actions,
      (2) according to recent studies ketamine could possess a unique intrinsic
      antidepressive potential and (3) ketamine may exhibit neuroprotective properties,
      which again might reduce the risk of cognitive side effects associated with ECT.
      OBJECTIVES: The use of ketamine in psychiatric patients has been controversially
      discussed due to its dose-dependent psychotropic and psychotomimetic effects.
      This study was carried out to test if the occurrence of side effects is
      comparable and if seizure quality is better with ketamine when compared to
      thiopental. MATERIAL AND METHODS: This retrospective study analyzed a total of
      199 patients who received ketamine anesthesia for a total of 2178 ECT sessions.
      This cohort was compared to patients who were treated with thiopental for 1004
      ECT sessions. RESULTS AND DISCUSSION: A repeated measurement multiple logistic
      regression analysis revealed significant advantages in the ketamine group for
      seizure concordance and postictal suppression (both are surrogates for central
      inhibition). S-ketamin also necessitated the use of a higher dose of urapidil and
      a higher maximum postictal heart frequency. Clinically relevant psychiatric side
      effects were rare in both groups. No psychiatric side effects occurred in the
      subgroup of patients with schizophrenia (ketamine: n = 30). The mean dose of S
      ketamine used increased in the first years but stabilized at 63 mg per patient in
      2014. From these experiences it can be concluded that S-ketamine can be
      recommended at least as a safe alternative to barbiturates.

PMID- 25943499
TI  - Citrinin Determination in Red Fermented Rice Products by Optimized Extraction
      Method Coupled to Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS).
AB  - A rapid and sensitive method was developed and validated for citrinin
      determination in red fermented rice products by liquid chromatography tandem mass
      spectrometry (LC-MS/MS) under the selected reaction monitoring mode. Sample
      preparation was especially focused, and the quantitative methods of LC-MS/MS and
      high-performance liquid chromatography with fluorescence detection (HPLC-FLD)
      were compared. In red fermented rice samples, the limit of detection was 1.0
      MUg/kg for LC-MS/MS compared to 250 MUg/kg for HPLC-FLD, the limit of
      quantification was 3.0 MUg/kg for LC-MS/MS compared to 825 MUg/kg for HPLC-FLD.
      High correlation coefficient was obtained (R(2) = 0.999) within the linear range
      (0.1 to 100 MUg/L) in the MS method. The recoveries ranging from 80.9% to 106.5%
      were obtained in different spiking concentrations. The average intra- and inter
      day accuracy ranged from 75.4% to 103.1%, and the intra- and inter-day precisions
      were from 3.3% to 7.9%. The developed method was applied to 12 commercial red
      fermented rice products, and citrinin was found in 10 samples ranging from 0.14
      to 44.24 mg/kg. Compared to traditional qualitative and quantitative methods, the
      newly developed LC-MS/MS method for citrinin determination includes the merits of
      using a small amount of extraction solvent, simple preparation steps, and high
      sensitivity. 

PMID- 25943500
TI  - Shaping a Subwavelength Needle with Ultra-long Focal Length by Focusing
      Azimuthally Polarized Light.
AB  - Flat optics, which could planarize and miniaturize the traditional optical
      elements, possesses the features of extremely low profile and high integration
      for advanced manipulation of light. Here we proposed and experimentally
      demonstrated a planar metalens to realize an ultra-long focal length of
      ~240lambda with a large depth of focus (DOF) of ~12lambda, under the illumination
      of azimuthally polarized beam with vortical phase at 633 nm. Equally important is
      that such a flat lens could stably keep a lateral subwavelength width of
      0.42lambda to 0.49lambda along the needle-like focal region. It exhibits one
      order improvement in the focal length compared to the traditional focal lengths
      of 20~30lambda of flat lens, under the criterion of having subwavelength focusing
      spot. The ultra-long focal length ensures sufficient space for subsequent
      characterization behind the lens in practical industry setups, while
      subwavelength cross section and large DOF enable high resolution in transverse
      imaging and nanolithography and high tolerance in axial positioning in the
      meantime. Such planar metalens with those simultaneous advantages is prepared by
      laser pattern generator rather than focused ion beam, which makes the mass
      production possible. 

PMID- 25943501
TI  - Neutrophil gelatinase-associated lipocalin attenuates injury in the rat cecal
      ligation and puncture model of sepsis via apoptosis inhibition.
AB  - AIM: The aim of this study was to investigate the effect of neutrophil gelatinase
      associated lipocalin (NGAL) on the rat cecal ligation and puncture (CLP)-induced
      sepsis and the possible mechanism. METHODS: Thirty male Sprague-Dawley rats
      underwent CLP as sepsis models and were randomized into three groups including
      the sham-operated group (sham, n = 10), which only underwent a laparotomy; the
      sepsis group (sepsis, n = 10), which underwent CLP and subcutaneous injection of
      normal saline; and the sepsis + NGAL group (sepsis + NGAL, n = 10), which
      underwent CLP and subcutaneous injection of NGAL. Urine, blood and kidney tissue
      samples were collected for the determination of urine NGAL (uNGAL), plasma NGAL
      (pNGAL), serum creatinine (Scr), blood urea nitrogen (BUN), histomorphological
      and immunohistochemical examination, lipid peroxidation product malondialdehyde
      (MDA) and superoxide dismutase (SOD), and expression of heme oxygenase-1 (HO)-1.
      RESULTS: The levels of uNGAL, pNGAL, Scr, BUN, kidney injury score, positive
      TUNEL staining, activated Caspase-3 and Bax, and kidney tissue MDA levels in the
      sepsis group were significantly increased compared with those in the sham
      operated group and the sepsis + NGAL group (P < 0.05). SOD level and HO-1
      expression in sepsis + NGAL group were significantly higher than those in the
      sham-operated group and the sepsis group (P < 0.05). CONCLUSION: NGAL can
      attenuate kidney injury and apoptosis in the rat CLP model of sepsis. And the
      protective effect of NGAL was probably due to the inhibition of apoptosis and
      lipid peroxidation, and increased expression of HO-1.

PMID- 25943502
TI  - The need for an objective measure in septorhinoplasty surgery: are we any closer
      to finding an answer?
AB  - OBJECTIVES: To assess the reliability of nasal inspiratory peak flow (NIPF) in
      providing a clinically accurate objective measure following functional
      septorhinoplasty by comparing it to the validated disease-specific quality-of
      life questionnaire, SNOT-22. Studies so far have demonstrated poor correlation
      between bilateral NIPF and symptom-specific nasal questionnaires following
      septorhinoplasty. DESIGN: To perform a prospective comparative analysis between
      NIPF and the validated disease-specific quality-of-life questionnaire SNOT-22 and
      to determine whether a correlation exists following septorhinoplasty surgery.
      SETTING: The Royal National Throat Nose and Ear Hospital, London. PARTICIPANTS: A
      total of 122 patients (78 males, 44 females; mean age 33.5 +/- 12.2 years) were
      recruited from the senior authors rhinology clinic and underwent functional
      septorhinoplasty surgery. MAIN OUTCOME MEASURES: Preoperative and postoperative
      nasal inspiratory peak flow (NIPF) measurements were performed in addition to the
      completion of three subjective quality-of-life and symptom assessment tool
      questionnaires; Sinonasal Outcome Test 22 (SNOT-22), Nasal Obstruction Symptom
      Evaluation (NOSE) and Visual Analogue Scale (VAS: 0-10). RESULTS: The mean
      preoperative NIPF was 88.2 L/min, and the postoperative value was 101.6 L/min and
      showed a significant improvement following surgery (P = 0.0064). The mean total
      SNOT-22 score improved significantly from 48.6 to 26.6 (P < 0.0001); the NOSE
      score from 14.1 to 6.6 (P < 0.0001); and the Visual Analogue Scale (VAS) blockage
      score from 6.9 to 3.2 (P < 0.0001). All individual domains assessed showed
      improvements postoperatively, but no correlation was found between the NIPF and
      SNOT-22 score. Equally, we did not find a correlation between NIPF and the
      symptom-specific NOSE questionnaire and the nasal blockage domain on the Visual
      Analogue Scale (VAS) scale. CONCLUSION: We have demonstrated that NIPF does not
      correlate with the SNOT-22 disease-specific questionnaire, although both outcomes
      significantly improve postoperatively. At present, we are still lacking a
      clinically accurate objective measure of nasal function for the evaluation of
      patients undergoing septorhinoplasty surgery.

PMID- 25943503
TI  - Regulation of Generic Drugs in Japan: the Current Situation and Future Prospects.
AB  - Generic drugs are interchangeable with original proprietary drugs, as they have
      the same active pharmaceutical ingredients, dosage forms, strength, quality,
      indications, effects, directions, and dosage. The cost of generic drugs is lower
      than original drugs, because the developmental cost is lower. The expansion of
      medical expenses is an important issue in many countries, including Japan, the
      USA, and Europe, and promotion of generic drugs has been demanded to solve this
      issue in Japan. Generic drug approval review in Japan is conducted by the
      Pharmaceuticals and Medical Devices Agency (PMDA), which reviews the equivalence
      of the original drugs from the viewpoint of quality, efficacy, and safety, based
      on documentation submitted by the generic drug applicants. However, the details
      of the generic drug review in Japan have not been reported. In this report, we
      introduce the application types, the number of applications and approvals, and
      the review timeline of generic drugs in Japan. In addition, we discuss recent
      consultations and future prospects. 

PMID- 25943504
TI  - Restricted accessed nanoparticles for direct magnetic solid phase extraction of
      trace metal ions from human fluids followed by inductively coupled plasma mass
      spectrometry detection.
AB  - Herein, restricted accessed magnetic nanoparticles were synthesized by self
      assembly of a non-ionic surfactant (Tween-20) onto the 4-(2-pyridylazo)resorcinol
      (PAR) functionalized magnetic nanoparticles (MNPs). A series of analytical
      techniques were employed for the characterization of the as-prepared restricted
      accessed Fe3O4@SiO2@PAR, and it was found that the as-prepared restricted
      accessed Fe3O4@SiO2@PAR nanoparticles have a porous structure with a BET surface
      area of around 99.4 m(2) g(-1), an average pore size of about 6.14 nm and a pore
      volume of 0.47 cm(3) g(-1). Besides, the prepared restricted accessed
      Fe3O4@SiO2@PAR showed good size exclusion properties toward proteins, providing
      application potential for the direct analysis of biological samples. Based on
      this, a novel method of restricted accessed magnetic solid phase extraction
      (MSPE) combined with inductively coupled plasma-mass spectrometry (ICP-MS) was
      developed for the direct determination of trace metal ions in human fluids. The
      parameters affecting the extraction of the target metals by MSPE were studied and
      the optimized conditions were established. Under the optimum conditions, the
      adsorption capacity of Cr(III), Cd(II), La(III), Nd(III) and Pb(II) on the as
      prepared restricted accessed Fe3O4@SiO2@PAR was 62.9, 56.6, 33.7, 36.9 and 43.3
      mg g(-1), respectively. With an enrichment factor of 30, the limits of detection
      for Cr(III), Cd(II), La(III), Nd(III) and Pb(II) were as low as 11.9, 0.8, 0.7,
      1.6 and 4.1 ng L(-1), and the relative standard deviations were 7.6, 8.7, 8.4,
      8.1 and 5.0 (C(Cr, Pb) = 0.05 MUg L(-1), C(Cd, La) = 0.005 MUg L(-1), C(Nd) =
      0.01 MUg L(-1), n = 7), respectively. The developed method was successfully
      applied for the direct analysis of free metal ions in human urine and serum
      samples, and has the advantages of good anti-interference ability, high
      sensitivity and exhibits great application potential in the direct analysis of
      trace metals in biological fluids.

PMID- 25943505
TI  - Effect of external phosphate addition on solid-phase iron distribution and iron
      accumulation in Mangrove Kandelia obovata (S. L.).
AB  - In this study, a pot experiment was conducted to evaluate the effect of phosphate
      (PO4 (3-)) addition on iron (Fe) cycling in mangrove ecosystem. Kandelia obovata
      (S. L.), one of the dominant mangrove species in the southeast of China, was
      cultivated in rhizoboxes under three different levels of P concentrations.
      Results showed the solid-phase Fe distribution and Fe(II)/Fe(III) values in both
      the root zone (rhizosphere) and bulk soil (non-rhizosphere) were comparable among
      all P levels (p > 0.05); P addition significantly decreased the pore water Fe
      content both in the rhizosphere and non-rhizosphere zone (p < 0.05); higher
      amount of reactive Fe was found in rhizosphere sediments, while in the non
      rhizosphere sediments, higher concentration of crystalline Fe was determined; P
      significantly increased iron plaque formation and iron accumulation in K. obovata
      (S. L.) tissues (p < 0.05); P addition increased K. obovata (S. L.) biomass and
      chlorophyll content. It was suggested that P is implicated in the Fe cycling in
      mangrove plants; more reactive iron, higher abundance of root Fe-reducing
      bacteria (FeRB) and Fe-oxidizing bacteria (FeOB), and together with higher amount
      of K. obovata (S. L.) root organic acids exudation result in a rapid Fe cycling
      in rhizosphere, which contribute to comparable solid-phase iron distribution
      among different P levels. 

PMID- 25943506
TI  - Effects of chitosan, gallic acid, and algicide on the physiological and
      biochemical properties of Microcystis flos-aquae.
AB  - The effects of chitosan, gallic acid, and algicide chitosan-gallate on the
      activities of antioxidant enzymes, malonaldehyde (MDA) content, and
      photosynthetic activity of Microcystis flos-aquae were investigated to explore
      the physiological and biochemical mechanisms of algicides. Results demonstrated
      that chitosan did not significantly affect catalase (CAT) and superoxide
      dismutase (SOD) activities, MDA content, and photosynthetic activity in this
      alga. At 30 mg L(-1), gallic acid, CAT, and SOD activities and MDA of M. flos
      aquae cells showed maximums of 2.872 * 10(-10) mg.cell(-1) min(-1), 0.787 * 10(
      8) U.cell(-1), and 0.626 * 10(-8) nmol.cell(-1), respectively. Photosynthetic
      organs in algal cells were severely damaged under the stress of high gallic acid
      concentrations, inducing blockage of photosynthetic electron transport and
      resulting in the inability to restore normal photosynthetic activity. CAT and SOD
      activities and MDA content with lower algicide concentration were significantly
      higher than the control group (p < 0.05) and, in higher algicide groups,
      significantly lower than the control (p < 0.05). Algicide releasing gallic acid
      in groups treated with 60, 90, and 130 mg/L algicide was strong enough to cause
      severe damage to photosynthetic organs in these algal cells. The algicide
      suppression time was longer than that of directly added gallic acid. 

PMID- 25943507
TI  - Nitric oxide mitigates arsenic-induced oxidative stress and genotoxicity in Vicia
      faba L.
AB  - The protective effects of nitric oxide (NO) against arsenic (As)-induced
      structural disturbances in Vicia faba have been investigated. As treatment (0.25,
      0.50, and 1 mM) resulted in a declined growth of V. faba seedlings. Arsenic
      treatment stimulates the activity of SOD and CAT while the activities of APX and
      GST content were decreased. The oxidative stress markers such as superoxide
      radical, hydrogen peroxide and malondialdehyde (lipid peroxidation) contents were
      enhanced by As. Overall results revealed that significant accumulation of As
      suppressed growth, photosynthesis, antioxidant enzymes (SOD, CAT, APX, and GST
      activity), mitotic index, and induction of different chromosomal abnormalities,
      hence led to oxidative stress. The concentration of SNP (0.02 mM) was very
      effective in counteracting the adverse effect of As toxicity. These abnormalities
      use partially or fully reversed by a simultaneous application of As and NO donor
      and sodium nitroprusside and has an ameliorating effect against As-induced
      oxidative stress and genotoxicity in V. faba roots. 

PMID- 25943509
TI  - Selenate removal by zero-valent iron in oxic condition: the role of Fe(II) and
      selenate removal mechanism.
AB  - In this study, batch experiments were conducted to investigate the effect of the
      concentration of ferrous [Fe(II)] ions on selenate [Se(VI)] removal using zero
      valent iron (ZVI). The mechanism of removal was investigated using spectroscopic
      and image analyses of the ZVI-Fe(II)-Se(VI) system. The test to remove 50 mg/L of
      Se(VI) by 1 g/L of ZVI resulted in about 60% removal of Se(VI) in the case with
      absence of Fe(II), but other tests with the addition of 50 and 100 mg/L of the
      Fe(II) had increased the removal efficiencies about 93 and 100% of the Se(VI),
      respectively. In other batch tests with the absence of ZVI, there were little
      changes on the Se(VI) removal by the varied concentration of the Fe(II). From
      these results, we found that Fe(II) ion plays an accelerator for the reduction of
      Se(VI) by ZVI with the stoichiometric balance of 1.4 (=nFe(2+)/nSe(6+)). Under
      anoxic conditions, the batch test revealed about 10% removal of the Se(VI),
      indicating that the presence of dissolved oxygen increased the kinetics of Se(VI)
      removal due to the Fe(II)-containing oxides on the ZVI, as analyzed by scanning
      electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDS) and X-ray
      photoelectron spectroscopy (XPS). The X-ray absorption near edge spectroscopy
      (XANES) and extended X-ray absorption fine structure (EXAFS) spectra also showed
      that the reductive process of Se(VI) to Se(0)/Se(-II) occurred in the presence of
      the both ZVI and Fe(II). The final product of iron corrosion was lepidocrocite
      (gamma-FeOOH), which acts as an electron transfer barrier from Fe(0) core to
      Se(VI). Therefore, the addition of Fe(II) enhanced the reactivity of ZVI through
      the formation of iron oxides (magnetite) favoring electron transfer during the
      removal of Se(VI), which was through the exhaustion of the Fe(0) core reacted
      with Se(VI).

PMID- 25943508
TI  - Thermal co-reduction approach to vary size of silver nanoparticle: its microbial
      and cellular toxicology.
AB  - In recent years, silver nanoparticles (AgNPs) have attracted considerable
      interest in the field of food, agriculture and pharmaceuticals mainly due to its
      antibacterial activity. AgNPs have also been reported to possess toxic behavior.
      The toxicological behavior of nanomaterials largely depends on its size and shape
      which ultimately depend on synthetic protocol. A systematic and detailed analysis
      for size variation of AgNP by thermal co-reduction approach and its efficacy
      toward microbial and cellular toxicological behavior is presented here. With the
      focus to explore the size-dependent toxicological variation, two different-sized
      NPs have been synthesized, i.e., 60 nm (Ag60) and 85 nm (Ag85). A detailed
      microbial toxicological evaluation has been performed by analyzing minimum
      inhibitory concentration (MIC), minimum bactericidal concentration (MBC),
      diameter of inhibition zone (DIZ), growth kinetics (GrK), and death kinetics
      (DeK). Comparative cytotoxicological behavior was analyzed by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. It has been
      concluded by this study that the size of AgNPs can be varied, by varying the
      concentration of reactants and temperature called as "thermal co-reduction"
      approach, which is one of the suitable approaches to meet the same. Also, the
      smaller AgNP has shown more microbial and cellular toxicity.

PMID- 25943510
TI  - Exposure to polycyclic aromatic hydrocarbons and assessment of potential risks in
      preschool children.
AB  - As children represent one of the most vulnerable groups in society, more
      information concerning their exposure to health hazardous air pollutants in
      school environments is necessary. Polycyclic aromatic hydrocarbons (PAHs) have
      been identified as priority air pollutants due to their mutagenic and
      carcinogenic properties that strongly affect human health. Thus, this work aims
      to characterize levels of 18 selected PAHs in preschool environment, and to
      estimate exposure and assess the respective risks for 3-5-year-old children (in
      comparison with adults). Gaseous PAHs (mean of 44.5 +/- 12.3 ng m(-3)) accounted
      for 87% of the total concentration (SigmaPAHs) with 3-ringed compounds being the
      most abundant (66% of gaseous SigmaPAHs). PAHs with 5 rings were the most
      abundant ones in the particulate phase (PM; mean of 6.89 +/- 2.85 ng m(-3)) being
      predominantly found in PM1 (78% particulate SigmaPAHs). Overall child exposures
      to PAHs were not significantly different between older children (4-5 years old)
      and younger ones (3 years old). Total carcinogenic risks due to particulate-bound
      PAHs indoors were higher than outdoor ones. The estimated cancer risks of both
      preschool children and the staff were lower than the United States Environmental
      Protection Agency (USEPA) threshold of 10(-6) but slightly higher than WHO-based
      guideline.

PMID- 25943511
TI  - Effect of biochars and microorganisms on cadmium accumulation in rice grains
      grown in Cd-contaminated soil.
AB  - Cadmium (Cd) contaminated in rice grains is a serious problem because most Asians
      consume rice on a daily basis. Rice grown in Cd-contaminated soil normally did
      not have high concentration of Cd. However, soil samples used in this study had
      high concentrations of Cd. The purpose of this study was to clearly see the
      effects of biochar and microorganism addition in rice growing in Cd-contaminated
      soil. The initial Cd concentration in Cd-contaminated soil used in this study was
      about 650 mg kg(-1). Cadmium concentration in rice plants grown in Cd
      contaminated soil with the addition of 1% (w/w) different biochars such as
      sawdust fly ash (SDFA), bagasse fly ash (BGFA), and rice husk ash (RHA) was
      investigated. The results showed that SDFA was the best biochar in terms of
      reducing cadmium accumulation in rice grains when compared to BGFA and RHA under
      the same conditions. In addition, rice plants grown in Cd-contaminated soil with
      the addition of various nonpathogenic microorganisms, such as Pseudomonas
      aeruginosa, Bacillus subtilis, and Beauveria bassiana were also studied. The
      results showed that the addition of 2% (v/v) microorganisms can reduce Cd
      accumulation in grains. It was found that grains obtained from Cd-contaminated
      soil with the addition of P. aeruginosa had the lowest cadmium concentration
      compared to the ones from soil amended with other strains. This was due to the
      fact that P. aeruginosa adsorbed more Cd itself into its cells than other
      strains. The rice plants grown in Cd-contaminated soil with the addition of
      biochars and microorganisms were also compared. The results showed that adding 2%
      (v/v) microorganisms seemed to reduce Cd accumulation in rice grains better than
      adding 1% (w/w) biochars. In addition, the amounts of calcium and magnesium in
      rice grains and the dry weight of plant in Cd-contaminated soil amended with P.
      aeruginosa were the highest in comparison to other microorganisms, biochars, and
      the soil without any amendments (Cd-soil control). It might be possible that
      microorganisms can cause leaching of Ca, Mg, etc. from contaminated soil and
      compete with Cd to be uptaken by plants. This would cause the increase in plant
      dry weight and higher mineral nutrients accumulation in grains. Both biochars and
      microorganisms are suitable for reducing the amount of Cd in rice grains. The
      application should depend on farmers, biochars available in nearby areas, etc.
      Therefore, microorganisms and biochars can be used to solve the problem of
      cadmium contamination in rice grains.

PMID- 25943513
TI  - Effects of waterborne nickel on the physiological and immunological parameters of
      the Pacific abalone Haliotis discus hannai during thermal stress.
AB  - In this study, the 96-h LC50 at 22 and 26  degrees C values was 28.591 and 11.761
      mg/L, respectively, for NiCl2 exposure in the abalone. The alteration of
      physiological and immune-toxicological parameters such as the total hemocyte
      count (THC), lysozyme, phenoloxidase (PO), and phagocytosis activity was measured
      in the abalone exposed to nickel (200 and 400 MUg/L) under thermal stress for 96
      h. In this study, Mg and THC decreased, while Ca, lysozyme, PO, and phagocytosis
      activity increased in the hemolymph of Pacific abalone exposed to NiCl2 when
      compared to a control at both 22 and 26  degrees C. However, these parameters
      were not affected by a rise in temperature from 22 to 26  degrees C in non
      exposed groups. Our results showed that NiCl2 below 400 MUg/L was able to
      stimulate immune responses in abalone. However, complex stressors, thermal
      changes, or NiCl2 can modify the immunological response and lead to changes in
      the physiology of host-pollutant interactions in the abalone. 

PMID- 25943512
TI  - Genotoxic potential of selected cytostatic drugs in human and zebrafish cells.
AB  - Due to their increasing use, the residues of anti-neoplastic drugs have become
      emerging pollutants in aquatic environments. Most of them directly or indirectly
      interfere with the cell's genome, which classifies them into a group of
      particularly dangerous compounds. The aim of the present study was to conduct a
      comparative in vitro toxicological characterisation of three commonly used
      cytostatics with different mechanisms of action (5-fluorouracil [5-FU], cisplatin
      [CDDP] and etoposide [ET]) towards zebrafish liver (ZFL) cell line, human
      hepatoma (HepG2) cells and human peripheral blood lymphocytes (HPBLs).
      Cytotoxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay and acridine orange/ethidium bromide
      staining. All three drugs induced time- and dose-dependent decreases in cell
      viability. The sensitivity of ZFL and HepG2 cells towards the cytotoxicity of 5
      FU was comparable (half maximal inhibitory concentration (IC50) 5.3 to 10.4
      MUg/mL). ZFL cells were more sensitive towards ET- (IC50 0.4 MUg/mL) and HepG2
      towards CDDP- (IC50 1.4 MUg/mL) induced cytotoxicity. Genotoxicity was determined
      by comet assay and cytokinesis block micronucleus (CBMN) assay. ZFL cells were
      the most sensitive, and HPBLs were the least sensitive. In ZFL cells, induction
      of DNA strand breaks was a more sensitive genotoxicity endpoint than micronuclei
      (MNi) induction; the lowest effective concentration (LOEC) for DNA strand break
      induction was 0.001 MUg/mL for ET, 0.01 MUg/mL for 5-FU and 0.1 MUg/mL for CDDP.
      In HepG2 cells, MNi induction was a more sensitive genotoxicity endpoint. The
      LOEC values were 0.01 MUg/mL for ET, 0.1 MUg/mL for 5-FU and 1 MUg/mL for CDDP.
      The higher sensitivity of ZFL cells to cytostatic drugs raises the question of
      the impact of such compounds in aquatic ecosystem. Since little is known on the
      effect of such drugs on aquatic organisms, our results demonstrate that ZFL cells
      provide a relevant and sensitive tool to screen genotoxic potential of
      environmental pollutant in the frame of hazard assessment. 

PMID- 25943514
TI  - Urea-induced oxidative damage in Elodea densa leaves.
AB  - Urea being a fertilizer is expected to be less toxic to plants. However, it was
      found that urea at 100 mg L(-1) caused the oxidative stress in Elodea leaves due
      to the formation of reactive oxygen species (ROS) and lipid peroxidation that are
      known to stimulate antioxidant pathway. Urea at a concentration of 500 and 1000
      mg L(-1) decreased low-molecular-weight antioxidants. In this case, the
      antioxidant status of plants was supported by the activity of antioxidant enzymes
      such as superoxide dismutase and guaiacol peroxidase. A significant increase in
      the soluble proteins and -SH groups was observed with high concentrations of urea
      (30-60 % of control). Thus, the increased activity of antioxidant enzymes, low
      molecular-weight antioxidants, and induced soluble protein thiols are implicated
      in plant resistance to oxidative stress imposed by urea. We found that guaiacol
      peroxidase plays an important role in the removal of the peroxide in Elodea
      leaves exposed to 1000 mg L(-1)of urea. 

PMID- 25943515
TI  - Urinary arsenic, heavy metals, phthalates, pesticides, polyaromatic hydrocarbons
      but not parabens, polyfluorinated compounds are associated with self-rated
      health: USA NHANES, 2011-2012.
AB  - Links between environmental chemicals and human health have emerged, but the
      effects on self-rated health were less studied. Therefore, it was aimed to study
      the relationships of different sets of urinary environmental chemicals and the
      self-rated health in a national and population-based study in recent years. Data
      was retrieved from the US National Health and Nutrition Examination Surveys, 2011
      2012, including demographics, serum measurements, lifestyle factors, self-rated
      health (with two grouping approaches) and urinary environmental chemical
      concentrations. T test and survey-weighted logistic regression modeling were
      performed. Among American adults aged 12-80 (n = 6833), 5892 people had reported
      their general health condition. Two thousand three hundred sixty-nine (40.2 %)
      people reported their general health condition as excellent or very good while
      3523 (59.8 %) reported good, fair, or poor. People who reported their general
      health condition as good, fair, or poor had higher levels of urinary arsenic,
      heavy metals (including cadmium, cobalt, manganese, molybdenum, lead, antimony,
      strontium, tungsten and uranium), phthalates, pesticides and polyaromatic
      hydrocarbons but lower levels of benzophenone-3 and triclosan. There were no
      associations with urinary parabens, perchlorate, nitrate, thiocyanate or
      polyfluorinated compounds. However, only urinary cadmium, benzophenone-3,
      triclosan, and 2-hydroxynaphthalene remained significant when comparing between
      "good to excellent" and "poor to fair." This is the first time observing risk
      associations of urinary arsenic, heavy metal, phthalate, pesticide, and
      hydrocarbon concentrations and self-rated health in people aged 12-80, although
      the causality cannot be established. Further elimination of these environmental
      chemicals in humans might need to be considered in health and environmental
      policies.

PMID- 25943516
TI  - The brown mussel Perna perna (L., 1758) as a sentinel species for chlorinated
      pesticide and dioxin-like compounds.
AB  - To contribute to the use of the tropical brown mussel Perna perna as a sentinel
      species for organochlorine pesticides (OCP) and polychlorinated biphenyls (PCB),
      the present study reports data on the toxicokinetics of these compounds in P.
      perna. Specifically, the authors present data on OCP and PCB bioaccumulation for
      eight sampling months from three bays (SE Brazil) and two transplant experiments
      (each 1 month long). Although seasonality is observed in the total lipid content
      of the whole soft tissue, with summer samples showing higher values, no such
      seasonality is observed in the OCP and PCB concentrations bioaccumulated by the
      mussel P. perna. Because no seasonal effect is observed in the annual OCP and PCB
      concentrations bioaccumulated by P. perna, the use of this species as a sentinel
      organism to monitor organochlorinated compounds is encouraged. One month of
      transplantation is not enough to allow the transplanted specimens to reach the
      concentrations observed in animals reared at the destination site. Nevertheless,
      P. perna showed a clear tendency to depurate the DDT metabolites p,p'-DDD and
      p,p'-DDE after 1 month of transplantation. 

PMID- 25943517
TI  - Investigation of gasoline distributions within petrol stations: spatial and
      seasonal concentrations, sources, mitigation measures, and occupationally exposed
      symptoms.
AB  - We measured levels of VOCs and determined the distributions of benzene
      concentrations over the area of two petrol stations in all three seasons. Using
      the concentrations and sampling positions, we created isoconcentration contour
      maps. The average concentrations ranged 18-1288 MUg m(-3) for benzene and 12-81
      MUg m(-3) for toluene. The contour maps indicate that high-level contours of
      benzene were found not only at the fuel dispenser areas but also at the storage
      tank refilling points, open drainage areas where gasoline-polluted wastewater was
      flowing, and the auto service center located within the station area. An
      assessment of the benzene to toluene ratio contour plots implicates that airborne
      benzene and toluene near the fuel dispenser area were attributed to gasoline
      evaporation although one of the studied stations may be influenced by other VOC
      sources besides gasoline evaporation. Additionally, during the routine refilling
      of the underground fuel storage tanks by a tank truck, the ambient levels of
      benzene and toluene increased tremendously. The implementation of source control
      by replacing old dispensers with new fuel dispensers that have an efficient
      cutoff feature and increased delivery speed can reduce spatial benzene
      concentrations by 77%. Furthermore, a questionnaire survey among 63 service
      attendants in ten stations revealed that headache was the most reported health
      complaint with a response rate of 32%, followed by fatigue with 20%. These
      prominent symptoms could be related to an exposure to high benzene
      concentrations.

PMID- 25943518
TI  - Evidence for the importance of litter as a co-substrate for MCPA dissipation in
      an agricultural soil.
AB  - Environmental controls of 2-methyl-4-chlorophenoxyacetic acid (MCPA) degradation
      are poorly understood. We investigated whether microbial MCPA degraders are
      stimulated by (maize) litter and whether this process depends on concentrations
      of MCPA and litter. In a microcosm experiment, different amounts of litter (0, 10
      and 20 g kg(-1)) were added to soils exposed to three levels of the herbicide (0,
      5 and 30 mg kg(-1)). The treated soils were incubated at 20  degrees C for 6
      weeks, and samples were taken after 1, 3 and 6 weeks of incubation. In soils with
      5 mg kg(-1) MCPA, about 50 % of the MCPA was dissipated within 1 week of the
      incubation. Almost complete dissipation of the herbicide had occurred by the end
      of the incubation with no differences between the three litter amendments. At the
      higher concentration (30 mg kg(-1)), MCPA endured longer in the soil, with only
      31 % of the initial amount being removed at the end of the experiment in the
      absence of litter. Litter addition greatly increased the dissipation rate with 70
      and 80 % of the herbicide being dissipated in the 10 and 20 g kg(-1) litter
      treatments, respectively. Signs of toxic effects of MCPA on soil bacteria were
      observed from related phospholipid fatty acid (PLFA) analyses, while fungi showed
      higher tolerance to the increased MCPA levels. The abundance of bacterial tfdA
      genes in soil increased with the co-occurrence of litter and high MCPA
      concentration, indicating the importance of substrate availability in fostering
      MCPA-degrading bacteria and thereby improving the potential for removal of MCPA
      in the environment.

PMID- 25943519
TI  - Efficiency and detrimental side effects of denitrifying bioreactors for nitrate
      reduction in drainage water.
AB  - A laboratory column experiment was conducted to test the efficiency of
      denitrifying bioreactors for the nitrate (NO3-N) removal in drainage waters at
      different flow rates and after desiccation. In addition, we investigated
      detrimental side effects in terms of the release of nitrite (NO2-N), ammonium
      (NH4-N), phosphate (PO4-P), dissolved organic carbon (DOC), methane (CH4), and
      dinitrogen oxide (N2O). The NO3-N removal efficiency decreased with increasing
      NO3-N concentrations, increasing flow rates, and after desiccation. Bioreactors
      with purely organic fillings showed higher NO3-N removal rates (42.6-55.7 g NO3-N
      m(-3) day(-1)) than those with organic and inorganic fillings (6.5-21.4 g NO3-N
      m(-3) day(-1)). The release of NO2-N and DOC was considerable and resulted in
      concentrations of up to 800 MUg NO2-N L(-1)and 25 mg DOC L(-1) in the effluent
      water. N2O concentrations increased by 4.0 to 15.3 MUg N2O-N L(-1) between the
      influent and the effluent, while CH4 production rates were low. Our study
      confirms the high potential of denitrifying bioreactors to mitigate NO3-N
      pollution in drainage waters, but highlights also the potential risks for the
      environment. 

PMID- 25943520
TI  - Maternal exposure to hexachlorophene targets intermediate-stage progenitor cells
      in the hippocampal neurogenesis involving myelin vacuolation of cholinergic and
      glutamatergic inputs in mice.
AB  - Hexachlorophene (HCP) has been shown to induce myelin vacuolation due to
      intramyelinic edema of the nerve fibers in animal neural tissue. We investigated
      the maternal exposure effect of HCP on hippocampal neurogenesis in the offspring
      of pregnant mice supplemented with 0 (control), 33 or 100 ppm HCP in diet from
      gestational day 6 to day 21 after delivery. On postnatal day (PND) 21, offspring
      as examined in males exhibited decreased granule cell lineage populations
      expressing paired box 6, sex-determining region Y-box 2 and eomesodermin in the
      hippocampal subgranular zone (SGZ) accompanied by myelin vacuolation involving
      white matter tracts of the hippocampal fimbria at >= 33 ppm. However, SGZ
      cellular populations expressing brain lipid binding protein and doublecortin were
      unchanged at any dose. Transcript expression of cholinergic receptor genes,
      Chrna4 and Chrnb2, and glutamate receptor genes, Grm1 and Grin2d, examined at 100
      ppm, decreased in the dentate gyrus. HCP exposure did not alter the number of
      proliferating or apoptotic cells in the SGZ, or reelin- or calcium-binding
      protein-expressing gamma-aminobutyric acid (GABA)ergic interneurons in the
      dentate hilus, on PND 21 and PND 77. All neurogenesis-related changes observed in
      HCP-exposed offspring on PND 21 disappeared on PND 77, suggesting that maternal
      HCP exposure at >= 33 ppm reversibly decreased type 2 intermediate-stage
      progenitor cells in the hippocampal neurogenesis. Myelin vacuolation might be
      responsible for changes in neurogenesis possibly by reducing nerve conduction
      velocity of cholinergic inputs from the septal-hippocampal pathway to granule
      cell lineages and/or GABAergic interneurons, and of glutamatergic inputs to
      granule cell lineages.

PMID- 25943521
TI  - Identification of QTLs for Rust Resistance in the Peanut Wild Species Arachis
      magna and the Development of KASP Markers for Marker-Assisted Selection.
AB  - Rust is a major pathogen of the peanut crop. Development and adoption of rust
      resistant cultivars is the most cost efficient and effective way to control the
      spread of the disease and reduce yield losses. Some cultivated peanut germplasm
      accessions have a degree of resistance, but the secondary gene pool is a source
      of much stronger resistance alleles. Wild species, however, have undesirable
      agronomic traits that are a disincentive to their use in breeding. The
      identification of genomic regions that harbor disease resistance in wild species
      is the first step in the implementation of marker-assisted selection that can
      speed the introgression of wild disease resistances and the elimination of
      linkage drag. In this work, we identify genome regions that control different
      components of rust resistance in a recombinant inbred line population developed
      from a cross between two Arachis species, the susceptible most probable B genome
      ancestor of cultivated peanut, Arachis ipaensis, and an accession of its closest
      relative, Arachis magna, which is resistant to rust. Quantitative trait loci for
      several components of resistance were placed in the same position on linkage
      group B08. Single-nucleotide polymorphism Kompetitive allele-specific polymerase
      chain reaction markers for rust resistance region were designed and validated for
      marker function in both diploid and tetraploid contexts. 

PMID- 25943522
TI  - Using the Animal Model to Accelerate Response to Selection in a Self-Pollinating
      Crop.
AB  - We used the animal model in S0 (F1) recurrent selection in a self-pollinating
      crop including, for the first time, phenotypic and relationship records from self
      progeny, in addition to cross progeny, in the pedigree. We tested the model in
      Pisum sativum, the autogamous annual species used by Mendel to demonstrate the
      particulate nature of inheritance. Resistance to ascochyta blight (Didymella
      pinodes complex) in segregating S0 cross progeny was assessed by best linear
      unbiased prediction over two cycles of selection. Genotypic concurrence across
      cycles was provided by pure-line ancestors. From cycle 1, 102/959 S0 plants were
      selected, and their S1 self progeny were intercrossed and selfed to produce 430
      S0 and 575 S2 individuals that were evaluated in cycle 2. The analysis was
      improved by including all genetic relationships (with crossing and selfing in the
      pedigree), additive and nonadditive genetic covariances between cycles, fixed
      effects (cycles and spatial linear trends), and other random effects. Narrow
      sense heritability for ascochyta blight resistance was 0.305 and 0.352 in cycles
      1 and 2, respectively, calculated from variance components in the full model. The
      fitted correlation of predicted breeding values across cycles was 0.82. Average
      accuracy of predicted breeding values was 0.851 for S2 progeny of S1 parent
      plants and 0.805 for S0 progeny tested in cycle 2, and 0.878 for S1 parent plants
      for which no records were available. The forecasted response to selection was
      11.2% in the next cycle with 20% S0 selection proportion. This is the first
      application of the animal model to cyclic selection in heterozygous populations
      of selfing plants. The method can be used in genomic selection, and for traits
      measured on S0-derived bulks such as grain yield. 

PMID- 25943526
TI  - Editorial: Can modern vaccine technology pursue the success of traditional
      vaccine manufacturing?

PMID- 25943523
TI  - Systematic Global Analysis of Genes Encoding Protein Phosphatases in Aspergillus
      fumigatus.
AB  - Aspergillus fumigatus is a fungal pathogen that causes several invasive and
      noninvasive diseases named aspergillosis. This disease is generally regarded as
      multifactorial, considering that several pathogenicity determinants are present
      during the establishment of this illness. It is necessary to obtain an increased
      knowledge of how, and which, A. fumigatus signal transduction pathways are
      engaged in the regulation of these processes. Protein phosphatases are essential
      to several signal transduction pathways. We identified 32 phosphatase catalytic
      subunit-encoding genes in A. fumigatus, of which we were able to construct 24
      viable deletion mutants. The role of nine phosphatase mutants in the HOG (high
      osmolarity glycerol response) pathway was evaluated by measuring phosphorylation
      of the p38 MAPK (SakA) and expression of osmo-dependent genes. We were also able
      to identify 11 phosphatases involved in iron assimilation, six that are related
      to gliotoxin resistance, and three implicated in gliotoxin production. These
      results present the creation of a fundamental resource for the study of signaling
      in A. fumigatus and its implications in the regulation of pathogenicity
      determinants and virulence in this important pathogen. 

PMID- 25943524
TI  - Tryptophan-Dependent Control of Colony Formation After DNA Damage via Sea3
      Regulated TORC1 Signaling in Saccharomyces cerevisiae.
AB  - The Saccharomyces cerevisiae Iml1 complex inhibits TORC1 signaling and SEACAT
      antagonizes the Iml1 complex. Conditions in which SEACAT functions to inhibit
      Iml1 and, hence, TORC1 signaling, remain largely unknown. The SEACAT member Sea3
      was linked previously to telomere maintenance and DNA repair via genome-wide
      genetic and physical interaction studies. Therefore, we questioned whether Sea3
      functioned through TORC1 to influence these pathways. Deletion of SEA3 delayed
      the emergence of telomerase-independent survivors that use break-induced
      replication (BIR) to maintain their telomeres. Similarly, sea3? mutants exhibited
      a delay in colony formation in a BIR assay strain after double-strand break (DSB)
      induction as well as on the DNA-damaging agent bleomycin. Deletion of IML1
      rescued the impaired growth of sea3? mutants after DNA damage, consistent with
      Sea3 functioning as a regulator of TORC1 signaling. The delay was not
      attributable to slowed DSB repair or termination of the DNA damage checkpoint but
      to tryptophan auxotrophy. High levels of tryptophan in yeast peptone dextrose
      media did not rescue the delay in colony formation, suggesting a defect in
      tryptophan import, although levels of the high-affinity tryptophan permease Tat2
      were not perturbed in the sea3Delta mutant. Addition of quinolinic acid, an
      intermediate of the de novo NAD+ biosynthetic pathway, however, rescued the delay
      in colony formation in the sea3Delta mutant. Together, these findings highlight
      the importance of enforcement of TORC1 signaling and suggest that internal
      tryptophan levels influence growth recovery post DNA damage through the role of
      tryptophan in NAD+ synthesis. 

PMID- 25943527
TI  - Human amniocyte-derived cells are a promising cell host for adenoviral vector
      production under serum-free conditions.
AB  - Recombinant adenovirus vectors (AdVs) have been used for the development of
      vaccines, as gene therapy vectors and for protein production. Currently, the
      production of clinical grade batches of recombinant E1-deleted adenovirus type 5
      vectors is performed using human-derived HEK293 or PER.C6((r)) cell lines. In
      this work we describe the generation of a new human amniocyte-derived cell line
      named 1G3 and show that it can be used as a very promising cell host for AdV
      production in serum-free conditions, allowing for production in high cell density
      cultures and avoiding the typical cell density effect observed for HEK293. By
      design, this cell line makes the generation of replication-competent adenovirus
      during production of E1-deleted AdVs very unlikely. The impact of the culture
      system (static versus agitated) and AdV infection parameters such as multiplicity
      of infection, time of harvesting and cell concentration at infection were
      evaluated and compared with HEK293. Using stirred tanks bioreactors, it was
      possible to grow 1G3 cells to cell densities of up to 9 * 10(6) cells/mL using
      serum-free media. Moreover, without a medium exchange step at infection, a three
      fold increase in AdV volumetric titers was obtained, as no cell density effect
      was observed at CCI 3. Overall, our results clearly demonstrate the potential of
      the human amniocyte-derived newly established cell line 1G3 for AdV production in
      a serum-free scalable process, paving the way for further process improvements
      based on fed-batch or perfusion strategies.

PMID- 25943530
TI  - Fatigue is frequent and severe in spinocerebellar ataxia type 1.

PMID- 25943531
TI  - Mass Spectrometry Imaging Analysis of Location of Procymidone in Cucumber
      Samples.
AB  - The localization of procymidone fungicide residue in cucumbers was investigated
      by mass spectrometry imaging (MSI). Cucumbers were grown, harvested, and then
      divided into two groups that were either sprayed or not sprayed with procymidone.
      The content of procymidone in the cucumbers was quantitatively determined by
      chromatographic techniques. Subsequently, the spatial distribution of procymidone
      was imaged by MSI. Procymidone reached the central part of the cucumbers
      following spraying compared with the control. 

PMID- 25943529
TI  - Association of cognitive domains with postural instability/gait disturbance in
      Parkinson's disease.
AB  - INTRODUCTION: Research suggests an association between global cognition and
      postural instability/gait disturbance (PIGD) in Parkinson disease (PD), but the
      relationship between specific cognitive domains and PIGD symptoms is not clear.
      This study examined the association of cognition (global and specific cognitive
      domains) with PIGD symptoms in a large, well-characterized sample of individuals
      with PD. METHODS: Cognitive function was measured with a detailed
      neuropsychological assessment, including global cognition, executive function,
      memory, visuospatial function, and language. PIGD symptoms were measured using
      the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS
      UPDRS) Part III, Motor Examination subscale. Multiple linear regression analyses
      were performed to assess the relationship between cognition and PIGD symptoms
      with models adjusting for age, sex, education, enrollment site, disease duration,
      and motor symptom severity. RESULTS: The analysis included 783 participants, with
      mean (standard deviation) age of 67.3 (9.7) years and median (interquartile
      range) MDS-UPDRS Motor Subscale score of 26 (17, 35). Deficits in global
      cognition, executive function, memory, and phonemic fluency were associated with
      more severe PIGD symptoms. Deficits in executive function were associated with
      impairments in gait, freezing, and postural stability, while visuospatial
      impairments were associated only with more severe freezing, and poorer memory
      function was associated only with greater postural instability. DISCUSSION: While
      impairments in global cognition and aspects of executive functioning were
      associated with more severe PIGD symptoms, specific cognitive domains were
      differentially related to distinct PIGD components, suggesting the presence of
      multiple neural pathways contributing to associations between cognition and PIGD
      symptoms in persons with PD.

PMID- 25943532
TI  - Survival Outcomes of Sipuleucel-T Phase III Studies: Impact of Control-Arm Cross
      Over to Salvage Immunotherapy.
AB  - Sipuleucel-T is an autologous cellular immunotherapy for asymptomatic/minimally
      symptomatic metastatic castrate-resistant prostate cancer (CRPC). After disease
      progression, control-arm patients on three double-blind, randomized phase III
      sipuleucel-T trials were offered, in nonrandomized open-label protocols,
      APC8015F, an autologous immunotherapy made from cells cryopreserved at the time
      of control manufacture. These exploratory analyses evaluated potential effects on
      survival outcomes associated with such treatment. Of 249 control-treated
      patients, 165 (66.3%) received APC8015F. We explored the effects of APC8015F on
      the overall survival (OS; Cox regression) of control-arm patients and treatment
      effects of sipuleucel-T versus control adjusted for APC8015F treatment [iterative
      parameter estimation model (IPE)]. The median time to first APC8015F infusion was
      5.2 months (range, 1.8-33.1) after randomization and 2.2 months (0.5-14.6) after
      progression. After disease progression, median survival was longer for APC8015F
      treated versus control-only treated patients [20.0 vs. 9.8 months; HR, 0.53; 95%
      confidence interval (CI), 0.38-0.74; P < 0.001]; however, baseline
      characteristics were more favorable for APC8015F-treated patients. Multivariate
      regression analyses identified lactate dehydrogenase, alkaline phosphatase,
      hemoglobin, ECOG status, age, and number of bone metastases as potential (P <
      0.1) independent predictors of postprogression survival. After adjusting for
      these predictors, APC8015F (HR, 0.78; 95% CI, 0.54-1.11; P = 0.17) treatment
      trended toward improved survival. Estimated median OS benefit for sipuleucel-T
      versus control adjusted for APC8015F treatment was 3.9 months if APC8015F had no
      effect and was 8.1 months if APC8015F was equally as effective as sipuleucel-T.
      Exploratory analyses indicate that APC8015F treatment may have extended patient
      survival, suggesting the sipuleucel-T OS advantage in CRPC may be more robust
      than previously estimated.

PMID- 25943533
TI  - Optimization of T-cell Reactivity by Exploiting TCR Chain Centricity for the
      Purpose of Safe and Effective Antitumor TCR Gene Therapy.
AB  - Adoptive transfer of T cells redirected by a high-affinity antitumor T-cell
      receptor (TCR) is a promising treatment modality for cancer patients. Safety and
      efficacy depend on the selection of a TCR that induces minimal toxicity and
      elicits sufficient antitumor reactivity. Many, if not all, TCRs possess cross
      reactivity to unrelated MHC molecules in addition to reactivity to target self
      MHC/peptide complexes. Some TCRs display chain centricity, in which recognition
      of MHC/peptide complexes is dominated by one of the TCR hemi-chains. In this
      study, we comprehensively studied how TCR chain centricity affects reactivity to
      target self-MHC/peptide complexes and alloreactivity using the TCR, clone TAK1,
      which is specific for human leukocyte antigen-A*24:02/Wilms tumor 1(235-243)
      (A24/WT1(235)) and cross-reactive with B*57:01 (B57). The TAK1beta, but not the
      TAK1alpha, hemi-chain possessed chain centricity. When paired with multiple
      clonotypic TCRalpha counter-chains encoding TRAV12-2, 20, 36, or 38-2, the de
      novo TAK1beta-containing TCRs showed enhanced, weakened, or absent reactivity to
      A24/WT1(235) and/or to B57. T cells reconstituted with these TCRalpha genes along
      with TAK1beta possessed a very broad range (>3 log orders) of functional and
      structural avidities. These results suggest that TCR chain centricity can be
      exploited to enhance desired antitumor TCR reactivity and eliminate unwanted TCR
      cross-reactivity. TCR reactivity to target MHC/peptide complexes and cross
      reactivity to unrelated MHC molecules are not inextricably linked and are
      separable at the TCR sequence level. However, it is still mandatory to carefully
      monitor for possible harmful toxicities caused by adoptive transfer of T cells
      redirected by thymically unselected TCRs.

PMID- 25943534
TI  - Identification and Characterization of MEDI4736, an Antagonistic Anti-PD-L1
      Monoclonal Antibody.
AB  - Programmed cell-death 1 ligand 1 (PD-L1) is a member of the B7/CD28 family of
      proteins that control T-cell activation. Many tumors can upregulate expression of
      PD-L1, inhibiting antitumor T-cell responses and avoiding immune surveillance and
      elimination. We have identified and characterized MEDI4736, a human IgG1
      monoclonal antibody that binds with high affinity and specificity to PD-L1 and is
      uniquely engineered to prevent antibody-dependent cell-mediated cytotoxicity. In
      vitro assays demonstrate that MEDI4736 is a potent antagonist of PD-L1 function,
      blocking interaction with PD-1 and CD80 to overcome inhibition of primary human T
      cell activation. In vivo MEDI4736 significantly inhibits the growth of human
      tumors in a novel xenograft model containing coimplanted human T cells. This
      activity is entirely dependent on the presence of transplanted T cells,
      supporting the immunological mechanism of action for MEDI4736. To further
      determine the utility of PD-L1 blockade, an anti-mouse PD-L1 antibody was
      investigated in immunocompetent mice. Here, anti-mouse PD-L1 significantly
      improved survival of mice implanted with CT26 colorectal cancer cells. The
      antitumor activity of anti-PD-L1 was enhanced by combination with oxaliplatin,
      which resulted in increased release of HMGB1 within CT26 tumors. Taken together,
      our results demonstrate that inhibition of PD-L1 function can have potent
      antitumor activity when used as monotherapy or in combination in preclinical
      models, and suggest it may be a promising therapeutic approach for the treatment
      of cancer. MEDI4736 is currently in several clinical trials both alone and in
      combination with other agents, including anti-CTLA-4, anti-PD-1, and inhibitors
      of IDO, MEK, BRAF, and EGFR.

PMID- 25943535
TI  - Single Institution Experience of Ipilimumab 3 mg/kg with Sargramostim (GM-CSF) in
      Metastatic Melanoma.
AB  - Ipilimumab, 10 mg/kg with sargramostim (GM-CSF; GM), improved overall survival
      (OS) and safety of patients with advanced melanoma over ipilimumab in a
      randomized phase II trial. The FDA-approved dose of ipilimumab of 3 mg/kg has not
      been assessed with GM (IPI-GM). Consecutive patients treated with IPI-GM at a
      single institution were reviewed. Treatment included ipilimumab every 3 weeks * 4
      and GM, 250-MUg s.c. injection days 1 to 14 of each ipilimumab cycle. Efficacy,
      clinical characteristics, toxicities, and blinded radiology review of tumor
      burden were evaluated. Thirty-two patients were identified with 25 (78%) having
      immune-related response criteria (irRC) measurable disease and 41% with central
      nervous system metastases. A total of 88.6% of GM doses were administered.
      Response rate by irRC and disease control rate at 12 weeks were 20% and 44%,
      respectively (median follow-up 37 weeks). Immune-related adverse events (irAE)
      were observed in 10 (31.3%) patients, with 3 (9.4%) grade 3 events. Patients with
      grade 3 irAEs had prior autoimmunity, advanced age, and poor performance status.
      The median OS from first dose of ipilimumab was 41 weeks. Ipi-GM treatment is
      feasible and in this poor-risk advanced melanoma population, efficacy appeared
      similar but safety appeared improved relative to historical ipilimumab alone.

PMID- 25943536
TI  - Effect of intentional abutment disconnection on the micro-movements of the
      implant-abutment assembly: a 3D digital image correlation analysis.
AB  - BACKGROUND: Implant-abutment assembly stability is critical for the success of
      implant-supported rehabilitation. The intentional removal of the prosthetic
      components may hamper the achievement of the essential stability due to preload
      reduction in the screw joint and implant-screw mating surface changes. OBJECTIVE:
      To evaluate the effect of intentional abutment disconnection and reconnection in
      the stability of internal locking hex implants and corresponding abutments using
      the method of 3D digital image correlation. MATERIAL AND METHODS: Ten conical
      shape and internal hexagon connection implants were embedded in acrylic resin and
      assembled to prosthetic abutments with 30 Ncm torque and assigned to two groups:
      group 1 - tested for static load-bearing capacity at 30 degrees  off-axis for two
      times and group 2 - underwent intentional disconnection and reconnection between
      tests. Micro-movements were captured with two high-speed photographic cameras and
      analyzed with video correlation system in three spacial axes U, V and W. Screw
      abutment and internal implant thread morphology was observed with a field
      emission scanning electron microscopy. RESULTS: After the intentional
      disconnection of the abutment, group 2 showed generally higher maximum
      displacements for U and V directions. Under 50N load, mean difference was 24.7
      MUm (P = 0.008) for U direction and -7.7 MUm (P = 0.008) for V direction. No
      significant differences were found for maximum and minimum displacements in the W
      direction. Mean displacement of the speckle surface presented was statistically
      different in the two groups (P = 0.016). SEM revealed non-homogenous screw
      surfaces with scoring on group 2 plus striations and debris in the implant
      threads. CONCLUSION: Micro-movements were higher for the group submitted to
      intentional disconnection and reconnection of the abutment, particularly under
      average bite forces.

PMID- 25943538
TI  - Orthostatic hypotension: a new cardiac risk factor?

PMID- 25943537
TI  - Implantable cardioverter defibrillators: even better than we thought?

PMID- 25943539
TI  - Cardiac sarcoma causing mechanical tamponade: a radiological dilemma!

PMID- 25943540
TI  - More transparency for a therapeutic window in platelet P2Y12 inhibition?

PMID- 25943542
TI  - Ethnoveterinary practices of Covasna County, Transylvania, Romania.
AB  - BACKGROUND: Ethnoveterinary medicine is a topic of growing interest among
      ethnobiologists, and is integral to the agricultural practices of many ethnic
      groups across the globe. The ethnoveterinary pharmacopoeia is often composed of
      ingredients available in the local environment, and may include plants, animals
      and minerals, or combinations thereof, for use in treating various ailments in
      reared animals. The aim of this study was to survey the current day
      ethnoveterinary practices of ethnic Hungarian (Szekely) settlements situated in
      the Erdovidek commune (Covasna County, Transylvania, Romania) and to compare them
      with earlier works on this topic in Romania and other European countries.
      METHODS: Data concerning ethnoveterinary practices were collected through semi
      structured interviews and direct observation in 12 villages from 2010 to 2014.
      The cited plant species were collected, identified, dried and deposited in a
      herbarium. The use of other materials (e.g. animals, minerals and other
      substances) were also documented. Data were compared to earlier reports of
      ethnoveterinary knowledge in Transylvania and other European countries using
      various databases. RESULTS: In total, 26 wild and cultivated plants, 2 animals,
      and 17 other substances were documented to treat 11 ailments of cattle, horses,
      pigs, and sheep. The majority of applications were for the treatment of mastitis
      and skin ailments, while only a few data were reported for the treatment of
      cataracts, post-partum ailments and parasites. The traditional uses of Armoracia
      rusticana, Rumex spp., powdered sugar and glass were reported in each village.
      The use of some plant taxa, such as Allium sativum, Aristolochia clematitis, and
      Euphorbia amygdaloides was similar to earlier reports from other Transylvanian
      regions. CONCLUSIONS: Although permanent veterinary and medical services are
      available in some of the villages, elderly people preferred the use of wild and
      cultivated plants, animals and other materials in ethnoveterinary medicine. Some
      traditional ethnoveterinary practices are no longer in use, but rather persist
      only in the memories of the eldest subset of the population. A decline in the
      vertical transmission of ethnoveterinary knowledge was evident and loss of
      practice is likely compounded by market availability of ready-made
      pharmaceuticals.

PMID- 25943541
TI  - Solitary pulmonary metastasis from prostate cancer with neuroendocrine
      differentiation: a case report and review of relevant cases from the literature.
AB  - BACKGROUND: Solitary lung metastasis from prostate cancer is rare. There are few
      reports of such cases with neuroendocrine differentiation. CASE PRESENTATION: A
      50-year-old man presented to our hospital with a chief complaint of dysuria.
      Histological examination revealed prostate cancer, which was classified as cT4 N0
      M0, stage IV adenocarcinoma. Since the patient was at high risk, endocrine and
      radiation therapies were started. One year after starting radiation therapy, the
      patient developed bloody sputum. Chest radiography revealed a nodular shadow in
      his left lung (S5). Although 18-fluoro-2-deoxyglucose positron emission
      tomography revealed abnormal accumulation in the lesion, the cytological
      diagnosis was class IIIa, which did not yield a definitive diagnosis. Given that
      prostate specific antigen (PSA) was not elevated, a primary lung tumor was
      suspected, and thoracoscopic segmental resection of the lung was performed with
      lymph node dissection. The final pathological diagnosis was solitary lung
      metastasis from prostate cancer with neuroendocrine differentiation and
      mediastinal lymph node metastasis. The specimen showed a mixed pattern of
      conventional prostatic and neuroendocrine carcinomas. CONCLUSION: We herein
      report a case with neuroendocrine differentiation (NED), along with a review of
      the relevant literature, including histopathological findings. According to
      previous case reports, some patients with solitary lung metastasis from prostate
      cancer achieved relatively good long-term survival. We consider establishing the
      correct diagnosis and implementing an appropriate treatment plan to be essential
      in prostate cancer patients with oligometastases that have the potential to be
      neuroendocrine (NE) tumors.

PMID- 25943543
TI  - TFmiR: a web server for constructing and analyzing disease-specific transcription
      factor and miRNA co-regulatory networks.
AB  - TFmiR is a freely available web server for deep and integrative analysis of
      combinatorial regulatory interactions between transcription factors, microRNAs
      and target genes that are involved in disease pathogenesis. Since the inner
      workings of cells rely on the correct functioning of an enormously complex system
      of activating and repressing interactions that can be perturbed in many ways,
      TFmiR helps to better elucidate cellular mechanisms at the molecular level from a
      network perspective. The provided topological and functional analyses promote
      TFmiR as a reliable systems biology tool for researchers across the life science
      communities. TFmiR web server is accessible through the following URL:
      http://service.bioinformatik.uni-saarland.de/tfmir. 

PMID- 25943545
TI  - CABS-dock web server for the flexible docking of peptides to proteins without
      prior knowledge of the binding site.
AB  - Protein-peptide interactions play a key role in cell functions. Their structural
      characterization, though challenging, is important for the discovery of new
      drugs. The CABS-dock web server provides an interface for modeling protein
      peptide interactions using a highly efficient protocol for the flexible docking
      of peptides to proteins. While other docking algorithms require pre-defined
      localization of the binding site, CABS-dock does not require such knowledge.
      Given a protein receptor structure and a peptide sequence (and starting from
      random conformations and positions of the peptide), CABS-dock performs simulation
      search for the binding site allowing for full flexibility of the peptide and
      small fluctuations of the receptor backbone. This protocol was extensively tested
      over the largest dataset of non-redundant protein-peptide interactions available
      to date (including bound and unbound docking cases). For over 80% of bound and
      unbound dataset cases, we obtained models with high or medium accuracy
      (sufficient for practical applications). Additionally, as optional features, CABS
      dock can exclude user-selected binding modes from docking search or to increase
      the level of flexibility for chosen receptor fragments. CABS-dock is freely
      available as a web server at http://biocomp.chem.uw.edu.pl/CABSdock. 

PMID- 25943544
TI  - FlyNet: a versatile network prioritization server for the Drosophila community.
AB  - Drosophila melanogaster (fruit fly) has been a popular model organism in animal
      genetics due to the high accessibility of reverse-genetics tools. In addition,
      the close relationship between the Drosophila and human genomes rationalizes the
      use of Drosophila as an invertebrate model for human neurobiology and disease
      research. A platform technology for predicting candidate genes or functions would
      further enhance the usefulness of this long-established model organism for gene
      to-phenotype mapping. Recently, the power of network prioritization for gene-to
      phenotype mapping has been demonstrated in many organisms. Here we present a
      network prioritization server dedicated to Drosophila that covers ~95% of the
      coding genome. This server, dubbed FlyNet, has several distinctive features,
      including (i) prioritization for both genes and functions; (ii) two complementary
      network algorithms: direct neighborhood and network diffusion; (iii)
      spatiotemporal-specific networks as an additional prioritization strategy for
      traits associated with a specific developmental stage or tissue and (iv)
      prioritization for human disease genes. FlyNet is expected to serve as a
      versatile hypothesis-generation platform for genes and functions in the study of
      basic animal genetics, developmental biology and human disease. FlyNet is
      available for free at http://www.inetbio.org/flynet. 

PMID- 25943546
TI  - (PS)2: protein structure prediction server version 3.0.
AB  - Protein complexes are involved in many biological processes. Examining coupling
      between subunits of a complex would be useful to understand the molecular basis
      of protein function. Here, our updated (PS)(2) web server predicts the three
      dimensional structures of protein complexes based on comparative modeling;
      furthermore, this server examines the coupling between subunits of the predicted
      complex by combining structural and evolutionary considerations. The predicted
      complex structure could be indicated and visualized by Java-based 3D graphics
      viewers and the structural and evolutionary profiles are shown and compared chain
      by-chain. For each subunit, considerations with or without the packing
      contribution of other subunits cause the differences in similarities between
      structural and evolutionary profiles, and these differences imply which form,
      complex or monomeric, is preferred in the biological condition for the subunit.
      We believe that the (PS)(2) server would be a useful tool for biologists who are
      interested not only in the structures of protein complexes but also in the
      coupling between subunits of the complexes. The (PS)(2) is freely available at
      http://ps2v3.life.nctu.edu.tw/. 

PMID- 25943547
TI  - HMMER web server: 2015 update.
AB  - The HMMER website, available at http://www.ebi.ac.uk/Tools/hmmer/, provides
      access to the protein homology search algorithms found in the HMMER software
      suite. Since the first release of the website in 2011, the search repertoire has
      been expanded to include the iterative search algorithm, jackhmmer. The continued
      growth of the target sequence databases means that traditional tabular
      representations of significant sequence hits can be overwhelming to the user.
      Consequently, additional ways of presenting homology search results have been
      developed, allowing them to be summarised according to taxonomic distribution or
      domain architecture. The taxonomy and domain architecture representations can be
      used in combination to filter the results according to the needs of a user.
      Searches can also be restricted prior to submission using a new taxonomic filter,
      which not only ensures that the results are specific to the requested taxonomic
      group, but also improves search performance. The repertoire of profile hidden
      Markov model libraries, which are used for annotation of query sequences with
      protein families and domains, has been expanded to include the libraries from
      CATH-Gene3D, PIRSF, Superfamily and TIGRFAMs. Finally, we discuss the relocation
      of the HMMER webserver to the European Bioinformatics Institute and the potential
      impact that this will have. 

PMID- 25943548
TI  - Cosmetics-triggered percutaneous remote control of transgene expression in mice.
AB  - Synthetic biology has significantly advanced the rational design of trigger
      inducible gene switches that program cellular behavior in a reliable and
      predictable manner. Capitalizing on genetic componentry, including the repressor
      PmeR and its cognate operator OPmeR, that has evolved in Pseudomonas syringae
      pathovar tomato DC3000 to sense and resist plant-defence metabolites of the
      paraben class, we have designed a set of inducible and repressible mammalian
      transcription-control devices that could dose-dependently fine-tune transgene
      expression in mammalian cells and mice in response to paraben derivatives. With
      an over 60-years track record as licensed preservatives in the cosmetics
      industry, paraben derivatives have become a commonplace ingredient of most skin
      care products including shower gels, cleansing toners and hand creams. As
      parabens can rapidly reach the bloodstream of mice following topical application,
      we used this feature to percutaneously program transgene expression of
      subcutaneous designer cell implants using off-the-shelf commercial paraben
      containing skin-care cosmetics. The combination of non-invasive, transdermal and
      orthogonal trigger-inducible remote control of transgene expression may provide
      novel opportunities for dynamic interventions in future gene and cell-based
      therapies. 

PMID- 25943549
TI  - CCTOP: a Consensus Constrained TOPology prediction web server.
AB  - The Consensus Constrained TOPology prediction (CCTOP;
      http://cctop.enzim.ttk.mta.hu) server is a web-based application providing
      transmembrane topology prediction. In addition to utilizing 10 different state-of
      the-art topology prediction methods, the CCTOP server incorporates topology
      information from existing experimental and computational sources available in the
      PDBTM, TOPDB and TOPDOM databases using the probabilistic framework of hidden
      Markov model. The server provides the option to precede the topology prediction
      with signal peptide prediction and transmembrane-globular protein discrimination.
      The initial result can be recalculated by (de)selecting any of the prediction
      methods or mapped experiments or by adding user specified constraints. CCTOP
      showed superior performance to existing approaches. The reliability of each
      prediction is also calculated, which correlates with the accuracy of the per
      protein topology prediction. The prediction results and the collected
      experimental information are visualized on the CCTOP home page and can be
      downloaded in XML format. Programmable access of the CCTOP server is also
      available, and an example of client-side script is provided. 

PMID- 25943550
TI  - An end-to-end hybrid algorithm for automated medication discrepancy detection.
AB  - BACKGROUND: In this study we implemented and developed state-of-the-art machine
      learning (ML) and natural language processing (NLP) technologies and built a
      computerized algorithm for medication reconciliation. Our specific aims are: (1)
      to develop a computerized algorithm for medication discrepancy detection between
      patients' discharge prescriptions (structured data) and medications documented in
      free-text clinical notes (unstructured data); and (2) to assess the performance
      of the algorithm on real-world medication reconciliation data. METHODS: We
      collected clinical notes and discharge prescription lists for all 271 patients
      enrolled in the Complex Care Medical Home Program at Cincinnati Children's
      Hospital Medical Center between 1/1/2010 and 12/31/2013. A double-annotated, gold
      standard set of medication reconciliation data was created for this collection.
      We then developed a hybrid algorithm consisting of three processes: (1) a ML
      algorithm to identify medication entities from clinical notes, (2) a rule-based
      method to link medication names with their attributes, and (3) a NLP-based,
      hybrid approach to match medications with structured prescriptions in order to
      detect medication discrepancies. The performance was validated on the gold
      standard medication reconciliation data, where precision (P), recall (R), F-value
      (F) and workload were assessed. RESULTS: The hybrid algorithm achieved
      95.0%/91.6%/93.3% of P/R/F on medication entity detection and 98.7%/99.4%/99.1%
      of P/R/F on attribute linkage. The medication matching achieved 92.4%/90.7%/91.5%
      (P/R/F) on identifying matched medications in the gold-standard and
      88.6%/82.5%/85.5% (P/R/F) on discrepant medications. By combining all processes,
      the algorithm achieved 92.4%/90.7%/91.5% (P/R/F) and 71.5%/65.2%/68.2% (P/R/F) on
      identifying the matched and the discrepant medications, respectively. The error
      analysis on algorithm outputs identified challenges to be addressed in order to
      improve medication discrepancy detection. CONCLUSION: By leveraging ML and NLP
      technologies, an end-to-end, computerized algorithm achieves promising outcome in
      reconciling medications between clinical notes and discharge prescriptions.

PMID- 25943551
TI  - Gaps in continuity of care: patients' perceptions of the quality of care during
      labor ward handover in Mulago hospital, Uganda.
AB  - BACKGROUND: Client satisfaction is a common outcome measure for quality of care
      and goal for quality improvement in healthcare. We assessed women's perceptions
      of the structure, process and outcome of intrapartum care in Mulago hospital,
      specifically, labor ward duty shift handovers. METHODS: Data was collected
      through 40 in-depth interviews conducted on two occasions: during the time of
      hospitalization and within 4-6 months after childbirth. Participants were women
      who delivered at the hospital, of whom some had life-threatening obstetric
      complications. Data was analyzed by thematic analysis. RESULTS: Maternity duty
      handovers were associated with patient dissatisfaction, particularly the process
      of hand-over, the decision-making that follows handovers and failure of
      communication of information to patients and their caretakers. Consequently, duty
      handovers were perceived inadequate. They were described as gaps in the
      continuity of care, and contributed to poor quality of care, birth trauma and
      mothers' dissatisfaction with the childbirth experience. CONCLUSION: The handover
      process and practices should be standardized using protocols and checklists.
      Health workers need training on handover practices, team work and communication
      skills (so as to improve patient-health provider and provider-provider
      interaction.

PMID- 25943552
TI  - Impact of extracardiac findings during cardiac MR on patient management and
      outcome.
AB  - BACKGROUND: Cardiac magnetic resonance (CMR) is increasingly used to assess heart
      diseases. Relevant non-cardiac diseases may also be incidentally found on CMR
      images. The aim of this study was to determine the prevalence and nature of
      incidental extra-cardiac findings (IEF) and their clinical impact in non-selected
      patients referred for CMR. MATERIAL/METHODS: MR images of 762 consecutive
      patients (515 men, age: 56+/-18 years) referred for CMR were prospectively
      interpreted by 2 radiologists blinded for any previous imaging study. IEFs were
      classified as major when requiring treatment, follow-up, or further
      investigation. Clinical follow-up was performed by checking hospital information
      records and by calling referring physicians. The 2 endpoints were: 1) non-cardiac
      death and new treatment related to major IEFs, and 2) hospitalization related to
      major IEFs during follow-up. RESULTS: Major IEFs were proven in 129 patients
      (18.6% of the study population), 14% of those being unknown before CMR. During
      15+/-6 month follow-up, treatment of confirmed major IEFs was initiated in 1.4%,
      and no non-cardiac deaths occurred. Hospitalization occurred in 8 patients (1.0%
      of the study population) with confirmed major IEFs and none occurred in the
      remaining 110 patients with unconfirmed/unexplored major IEFs (p<0.001).
      CONCLUSIONS: Screening for major IEFs in a population referred for routine CMR
      changed management in 1.4% of patients. Major IEFs unknown before CMR but without
      further exploration, however, carried a favorable prognosis over a follow-up
      period of 15 months.

PMID- 25943553
TI  - Does the availability of a South Asian language in practices improve reports of
      doctor-patient communication from South Asian patients? Cross sectional analysis
      of a national patient survey in English general practices.
AB  - BACKGROUND: Ethnic minorities report poorer evaluations of primary health care
      compared to White British patients. Emerging evidence suggests that when a doctor
      and patient share ethnicity and/or language this is associated with more positive
      reports of patient experience. Whether this is true for adults in English general
      practices remains to be explored. METHODS: We analysed data from the 2010/2011
      English General Practice Patient Survey, which were linked to data from the NHS
      Choices website to identify languages which were available at the practice. Our
      analysis was restricted to single-handed practices and included 190,582 patients
      across 1,068 practices. Including only single-handed practices enabled us to
      attribute, more accurately, reported patient experience to the languages that
      were listed as being available. We also carried out sensitivity analyses in multi
      doctor practices. We created a composite score on a 0-100 scale from seven survey
      items assessing doctor-patient communication. Mixed-effect linear regression
      models were used to examine how differences in reported experience of doctor
      communication between patients of different self-reported ethnicities varied
      according to whether a South Asian language concordant with their ethnicity was
      available in their practice. Models were adjusted for patient characteristics and
      a random effect for practice. RESULTS: Availability of a concordant language had
      the largest effect on communication ratings for Bangladeshis and the least for
      Indian respondents (p < 0.01). Bangladeshi, Pakistani and Indian respondents on
      average reported poorer communication than White British respondents [-2.9 (95%CI
      -4.2, -1.6), -1.9 (95%CI -2.6, -1.2) and -1.9 (95%CI -2.5, -1.4), respectively].
      However, in practices where a concordant language was offered, the experience
      reported by Pakistani patients was not substantially worse than that reported by
      White British patients (-0.2, 95%CI -1.5,+1.0), and in the case of Bangladeshi
      patients was potentially much better (+4.5, 95%CI -1.0,+10.1). This contrasts
      with a worse experience reported among Bangladeshi (-3.3, 95%CI -4.6, -2.0) and
      Pakistani (-2.7, 95%CI -3.6, -1.9) respondents when a concordant language was not
      offered. CONCLUSIONS: Substantial differences in reported patient experience
      exist between ethnic groups. Our results suggest that patient experience among
      Bangladeshis and Pakistanis is improved where the practice offers a language that
      is concordant with the patient's ethnicity.

PMID- 25943554
TI  - Impact of preoperative use of P2Y12 receptor inhibitors on clinical outcomes in
      cardiac and non-cardiac surgery: A systematic review and meta-analysis.
AB  - OBJECTIVE: To review systematically the evidence and perform a meta-analysis of
      benefits and risks associated with use of P2Y12 receptor inhibitors in coronary
      artery bypass graft-, non-cardiac- and device surgery. Data selection and
      analysis: We performed a meta-analysis of published studies. Patients with
      preoperative use of clopidogrel, ticagrelor or prasugrel (late discontinuation:
      <5 days before surgery or no discontinuation) were compared with patients without
      preoperative use of the respective drug (early discontinuation: ?5 days before
      surgery or no users of P2Y12 receptor inhibitors). Outcomes evaluated were re
      operation for major bleeding, death, myocardial infarction, combined major
      adverse cardiac events (MACEs) and major haematoma. Using a random effect model,
      relative risks (RRs) and 95% confidence intervals (CI) were calculated for each
      outcome. RESULTS: Fifty-four studies met the selection criteria and included
      50,048 patients. Preoperative use of clopidogrel on top of aspirin in patients
      undergoing coronary artery bypass graft was associated with a 2.5-fold increased
      risk of re-operation for bleeding (95% CI: 1.92-3.25; p<0.001) and a 1.47-fold
      increased risk of death (95% CI: 1.25-1.72; p<0.001), but did not diminish the
      risk for myocardial infarction (RR: 0.96; 95% CI: 0.75-1.25; p=0.18) or MACE (RR:
      1.16; 95% CI: 0.90--1.50; p=0.30). In patients undergoing non-cardiac surgery,
      preoperative use of clopidogrel increased the RR of re-operation for major
      bleeding by 2.05-fold (95% CI: 1.13-3.73; p=0.002) but did not reduce the RR for
      MACE or death. Clopidogrel use during cardiac device implantation raised the RR
      for procedure-related haematoma by 3.0-fold (95% CI: 1.30--6.94; p=0.001).
      Whereas preoperative ticagrelor use did not increase the risk for mortality (RR:
      1.03; 95% CI: 0.49-2.14), preoperative prasugrel use tended to increase the risk
      for death (RR: 5.06; 95% CI: 0.54-47.65). CONCLUSION: Preoperative exposure to
      clopidogrel on top of aspirin did not reduce the risk of MACE but was associated
      with increased risk of bleeding and mortality.

PMID- 25943555
TI  - Editor's Choice-Is the pre-hospital ECG after out-of-hospital cardiac arrest
      accurate for the diagnosis of ST-elevation myocardial infarction?
AB  - BACKGROUND: Current guidelines recommend that comatose out-of-hospital cardiac
      arrest patients with ST-segment elevations (STEs) following return of spontaneous
      circulation (ROSC) should be referred for an acute coronary angiography. We
      sought to investigate the diagnostic value of the pre-hospital ROSC-ECG in
      predicting ST-elevation myocardial infarction (STEMI). METHOD: ROSC-ECGs of 145
      comatose survivors of out-of-hospital cardiac arrest, randomly assigned in the
      Target Temperature Management trial, were classified according to the current
      STEMI ECG criteria (third universal definition of myocardial infarction).
      RESULTS: STEs were present in the pre-hospital ROSC-ECG of 78 (54%) patients. A
      final diagnosis revealed that 69 (48%) patients had STEMI, 31 (21%) patients had
      non-STEMI and 45 (31%) patients had no myocardial infarction. STE in ROSC-ECGs
      had a sensitivity of 74% (95% confidence interval (CI) 62-84), specificity of 65%
      (95% CI 53-75) and a positive and negative predictive value of 65% (95% CI 54-76)
      and 73% (95% CI 61-83) in predicting STEMI. Time to ROSC was significantly longer
      (24 minutes vs. 19 minutes, P=0.02) in STE compared with no STE patients.
      Percutaneous coronary intervention was successful in 68% versus 36% (P<0.001) of
      STE compared to no STE patients. No significant difference was found in 180-day
      mortality rates between STE and no STE patients (36% vs. 30%, Plogrank=0.37).
      CONCLUSION: The pre-hospital ROSC-ECG is a suboptimal diagnostic tool to predict
      STEMI and therefore not a sensitive tool for triage to cardiac centres. This
      supports the incentive of referring all comatose survivors of out-of-hospital
      cardiac arrest of suspected cardiac origin to a tertiary heart centre with the
      availability of acute coronary angiography, even in the absence of STEs.

PMID- 25943556
TI  - The use of discharge haemoglobin and NT-proBNP to improve short and long-term
      outcome prediction in patients with acute heart failure.
AB  - AIMS: To examine the prognostic value of admission (A) and discharge (D)
      haemoglobin (Hb) and its relationship with N-terminal pro-hormone B-type
      natriuretic peptide (NT-proBNP) in patients hospitalised for acute heart failure
      (AHF). The outcomes of interests were rehospitalisation or death after one, six
      or twelve months after discharge. METHODS: 317 hospitalised AHF patients (74.7+/
      9.4 years) were enrolled in two academic centres in Belgrade and Rome. Laboratory
      analyses, including NT-proBNP were assessed at admission, and Hb also at
      discharge. Patients were divided into two groups according to the presence of
      anaemia. Follow-up contact was made by telephone. Statistical analyses were
      performed using SPSS software version 21.0. RESULTS: According to A and DHb
      levels (<120 g/l for women and <130 g/l for men), anaemia was present in 55% and
      62% of patients, respectively ( P=0.497). Lower DHb was associated with the
      rehospitalisation risk after one (OR=0.96, P=0.004), six (OR=0.97, P<0.001) and
      12 months (OR=0.97, P<0.001). For every g/l decrease of DHb, the risk of
      rehospitalisation after one year was increased by 3.3%. In the first six months,
      DHb contributed to increased risk of death (OR=0.97, P=0.005), but NT-proBNP
      showed greater power (OR=2.1, P<0.001). CONCLUSIONS: In AHF patients discharge
      anaemia is a strong predictor for short and long-term rehospitalisation, while NT
      proBNP seems to be a better predictor for mortality. Discharge Hb and NT-proBNP
      should be assessed together in order to detect the patients with higher risk of
      future death and rehospitalisation.

PMID- 25943557
TI  - Kinetics of high-sensitivity cardiac troponin T and I differ in patients with ST
      segment elevation myocardial infarction treated by primary coronary intervention.
AB  - PURPOSE: Cardiac biomarkers including troponins are the cornerstone of the
      biological definition of acute myocardial infarction. New high-sensitivity
      cardiac assays determining troponin T (hs-cTnT) as well as I ((hs-cTnI) from
      Abbott and s-cTnI from Siemens) raise concerns because of their unclear kinetics
      following the peak. AIMS: This study aims to compare kinetics of creatine
      kinases, hs-cTnT, hs-cTnI and s-cTnI in patients with ST-segment elevation
      myocardial infarction (STEMI) treated by percutaneous coronary intervention.
      METHODS: We prospectively studied 106 consecutive patients admitted in our
      institution for STEMI and treated by percutaneous coronary intervention. We
      evaluated for all the patients simultaneously kinetics of creatine kinases, hs
      cTnT (Roche) and two different cTnIs (hs-cTnI from Abbott and s-cTnI from
      Siemens). Modelling of kinetics was realized using mixed effects with cubic
      splines. RESULTS: Kinetics of markers showed a first peak at 10.7h (8.0-12.0) for
      creatine kinases, 11.8h (10.4-13.3) for hs-cTnT (Roche); 11.8h (10.7-11.8) for hs
      cTnI from Abbott and 10.2h (8.7-11.6) for s-cTnI from Siemens, respectively. This
      peak was followed by a nearly log linear decrease for hs-cTnI/s-cTnI and creatine
      kinases in contrast to hs-cTnT, which appeared with a biphasic shape curve marked
      by a second peak at 76.9h (69.5-82.8). The analysis of the decrease in percentage
      of the peak value at 77h showed that hs-cTnT follows a twice lower decrease than
      other markers. CONCLUSION: Kinetics of hs-cTnT, hs-cTnI and s-cTnI differ
      significantly with a linear decrease regarding both cTnI assays contrasting with
      a biphasic shape curve for hs-cTnT. This is of importance for clinical management
      of patients in routine settings especially in follow-up after STEMI including the
      suspicion of reinfarction.

PMID- 25943558
TI  - Ocular neuropathic pain.
AB  - As the biological alarm of impending or actual tissue damage, pain is essential
      for our survival. However, when it is initiated and/or sustained by dysfunctional
      elements in the nociceptive system, it is itself a disease known as neuropathic
      pain. While the critical nociceptive system provides a number of protective
      functions, it is unique in its central role of monitoring, preserving and
      restoring the optical tear film in the face of evaporative attrition without
      which our vision would be non-functional. Meeting this existential need resulted
      in the evolution of the highly complex, powerful and sensitive dry eye alarm
      system integrated in the peripheral and central trigeminal sensory network. The
      clinical consequences of corneal damage to these nociceptive pathways are
      determined by the type and location of its pathological elements and can range
      from the spectrum known as dry eye disease to the centalised oculofacial
      neuropathic pain syndrome characterised by a striking disparity between the high
      intensity of symptoms and paucity of external signs. These changes parallel those
      observed in somatic neuropathic pain. When seen through the neuroscience lens,
      diseases responsible for inadequately explained chronic eye pain (including those
      described as dry eye) can take on new meanings that may clarify long-standing
      enigmas and point to new approaches for developing preventive, symptomatic and
      disease-modifying interventions for these currently refractory disorders. 

PMID- 25943559
TI  - Non-uniqueness of factors constraint on the codon usage in Bombyx mori.
AB  - BACKGROUND: The analysis of codon usage is a good way to understand the genetic
      and evolutionary characteristics of an organism. However, there are only a few
      reports related with the codon usage of the domesticated silkworm, Bombyx mori
      (B. mori). Hence, the codon usage of B. mori was analyzed here to reveal the
      constraint factors and it could be helpful to improve the bioreactor based on B.
      mori. RESULTS: A total of 1,097 annotated mRNA sequences from B. mori were
      analyzed, revealing there is only a weak codon bias. It also shows that the gene
      expression level is related to the GC content, and the amino acids with higher
      general average hydropathicity (GRAVY) and aromaticity (Aromo). And the genes on
      the primary axis are strongly positively correlated with the GC content, and
      GC3s. Meanwhile, the effective number of codons (ENc) is strongly correlated with
      codon adaptation index (CAI), gene length, and Aromo values. However, the ENc
      values are correlated with the second axis, which indicates that the codon usage
      in B. mori is affected by not only mutation pressure and natural selection, but
      also nucleotide composition and the gene expression level. It is also associated
      with Aromo values, and gene length. Additionally, B. mori has a greater relative
      discrepancy in codon preferences with Drosophila melanogaster (D. melanogaster)
      or Saccharomyces cerevisiae (S. cerevisiae) than with Arabidopsis thaliana (A.
      thaliana), Escherichia coli (E. coli), or Caenorhabditis elegans (C. elegans).
      CONCLUSIONS: The codon usage bias in B. mori is relatively weak, and many
      influence factors are found here, such as nucleotide composition, mutation
      pressure, natural selection, and expression level. Additionally, it is also
      associated with Aromo values, and gene length. Among them, natural selection
      might play a major role. Moreover, the "optimal codons" of B. mori are all
      encoded by G and C, which provides useful information for enhancing the gene
      expression in B. mori through codon optimization.

PMID- 25943561
TI  - A metabolomic study of the PPARdelta agonist GW501516 for enhancing running
      endurance in Kunming mice.
AB  - Exercise can increase peroxisome proliferator-activated receptor-delta
      (PPARdelta) expression in skeletal muscle. PPARdelta regulates muscle metabolism
      and reprograms muscle fibre types to enhance running endurance. This study
      utilized metabolomic profiling to examine the effects of GW501516, a PPARdelta
      agonist, on running endurance in mice. While training alone increased the
      exhaustive running performance, GW501516 treatment enhanced running endurance and
      the proportion of succinate dehydrogenase (SDH)-positive muscle fibres in both
      trained and untrained mice. Furthermore, increased levels of intermediate
      metabolites and key enzymes in fatty acid oxidation pathways were observed
      following training and/or treatment. Training alone increased serum inositol,
      glucogenic amino acids, and branch chain amino acids. However, GW501516 increased
      serum galactose and beta-hydroxybutyrate, independent of training. Additionally,
      GW501516 alone raised serum unsaturated fatty acid levels, especially
      polyunsaturated fatty acids, but levels increased even more when combined with
      training. These findings suggest that mechanisms behind enhanced running capacity
      are not identical for GW501516 and training. Training increases energy
      availability by promoting catabolism of proteins, and gluconeogenesis, whereas
      GW501516 enhances specific consumption of fatty acids and reducing glucose
      utilization. 

PMID- 25943560
TI  - GH action influences adipogenesis of mouse adipose tissue-derived mesenchymal
      stem cells.
AB  - GH influences adipocyte differentiation, but both stimulatory and inhibitory
      effects have been described. Adipose tissue-derived mesenchymal stem cells (AT
      MSCs) are multipotent and are able to differentiate into adipocytes, among other
      cells. Canonical Wnt/beta-catenin signaling activation impairs adipogenesis. The
      aim of the present study was to elucidate the role of GH on AT-MSC adipogenesis
      using cells isolated from male GH receptor knockout (GHRKO), bovine GH transgenic
      (bGH) mice, and wild-type littermate control (WT) mice. AT-MSCs from subcutaneous
      (sc), epididiymal (epi), and mesenteric (mes) AT depots were identified and
      isolated by flow cytometry (Pdgfralpha+ Sca1+ Cd45- Ter119- cells). Their in
      vitro adipogenic differentiation capacity was determined by cell morphology and
      real-time RT-PCR. Using identical in vitro conditions, adipogenic differentiation
      of AT-MSCs was only achieved in the sc depot, and not in epi and mes depots.
      Notably, we observed an increased differentiation in cells isolated from sc-GHRKO
      and an impaired differentiation of sc-bGH cells as compared to sc-WT cells.
      Axin2, a marker of Wnt/beta-catenin activation, was increased in mature sc-bGH
      adipocytes, which suggests that activation of this pathway may be responsible for
      the decreased adipogenesis. Thus, the present study demonstrates that (i) adipose
      tissue in mice has a well-defined population of Pdgfralpha+ Sca1+ MSCs; (ii) the
      differentiation capacity of AT-MSCs varies from depot to depot regardless of GH
      genotype; (iii) the lack of GH action increases adipogenesis in the sc depot; and
      iv) activation of the Wnt/beta-catenin pathway might mediate the GH effect on AT
      MSCs. Taken together, the present results suggest that GH diminishes fat mass in
      part by altering adipogenesis of MSCs.

PMID- 25943562
TI  - Dissolved carbon dioxide determines the productivity of a recombinant
      hemagglutinin component of an influenza vaccine produced by insect cells.
AB  - Dissolved carbon dioxide (dCO2 ) accumulation during cell culture has been
      recognized as an important parameter that needs to be controlled for successful
      scale-up of animal cell culture because above a certain concentration there are
      adverse effects on cell growth performance and protein production. We
      investigated the effect of accumulation of dCO2 in bioreactor cultures of
      expresSF+((r)) insect cells infected with recombinant baculoviruses expressing
      recombinant influenza virus hemagglutinins (rHA). Different strategies for
      bioreactor cultures were used to obtain various ranges of concentrations of dCO2
      (<50, 50-100, 100-200, and >200 mmHg) and to determine their effects on
      recombinant protein production and cell metabolic activity. We show that the
      accumulation of dCO2 at levels > 100 mmHg resulted in reduced metabolic activity,
      slowed cell growth, prolonged culture viability after infection, and decreased
      infection kinetics. The reduced rHA yields were not caused by the decrease in the
      extracellular pH that resulted from dCO2 accumulation, but were most likely due
      to the effect of dCO2 accumulation in cells. The results obtained here at the 2 L
      scale have been used for the design of large-scale processes to manufacture the
      rHA based recombinant vaccine FlublokTM at the 2500 L scale Biotechnol. Bioeng.
      2015;112: 2267-2275. (c) 2015 Wiley Periodicals, Inc. 

PMID- 25943563
TI  - Controlled Self-Assembly of Proteins into Discrete Nanoarchitectures Templated by
      Gold Nanoparticles via Monovalent Interfacial Engineering.
AB  - Designed rational assembly of proteins promises novel properties and
      functionalities as well as new insights into the nature of life. De novo design
      of artificial protein nanostructures has been achieved using protein subunits or
      peptides as building blocks. However, controlled assembly of protein
      nanostructures into higher-order discrete nanoarchitectures, rather than infinite
      arrays or aggregates, remains a challenge due to the complex or symmetric surface
      chemistry of protein nanostructures. Here we develop a facile strategy to control
      the hierarchical assembly of protein nanocages into discrete nanoarchitectures
      with gold nanoparticles (AuNPs) as scaffolds via rationally designing their
      interfacial interaction. The protein nanocage is monofunctionalized with a
      polyhistidine tag (Histag) on the external surface through a mixed assembly
      strategy, while AuNPs are modified with Ni(2+)-NTA chelates, so that the protein
      nanocage can controllably assemble onto the AuNPs via the Histag-Ni(2+) affinity.
      Discrete protein nanoarchitectures with tunable composition can be generated by
      stoichiometric control over the ratio of protein nanocage to AuNP or change of
      AuNP size. The methodology described here is extendable to other protein
      nanostructures and chemically synthesized nanomaterials, and can be borrowed by
      synthetic biology for biomacromolecule manipulation. 

PMID- 25943564
TI  - Methylene blue attenuates acute liver injury induced by paraquat in rats.
AB  - Paraquat (PQ) poisoning often leads to severe oxidative liver injury. Recent
      studies have reported that methylene blue (MB) can prevent oxidative stress
      induced diseases. This study tested the hypothesis that MB treatment reduced
      acute liver injury induced by PQ in rats. Adult male Sprague-Dawley (SD) rats
      were randomly divided into four groups: (1) normal group, (2) MB group (2mg/kg
      i.p.), (3) PQ group (35 mg/kg i.p.) and (4) PQ+MB group (MB 2mg/kg i.p.
      administrated 2h after PQ). We evaluated the changes of liver histopathology,
      serum liver enzymatic activities, oxidative stress, heme oxygenase-1 expression,
      and mitochondrial permeability transition. The rats were injected with PQ
      produced liver injury, evidenced by histological changes and elevated serum
      alkaline phosphatase and alanine transaminase levels; PQ also led to oxidative
      stress, an increase of malondialdehyde content and mitochondrial permeability
      transition pore opening. Pathological damage and all of the above mentioned
      markers were reversed in the animals treated with MB than in those who received
      PQ alone. Meanwhile, MB significantly increased the contents of superoxide
      dismutase, adenosine triphosphate and the expression of heme oxygenase-1. In
      conclusion, MB had a protective effect against PQ-induced hepatic damage in rats.
      The mechanisms of the protection seem to be the inhibition of mitochondrial
      permeability transition opening and the increase of heme oxygenase-1 expression.

PMID- 25943565
TI  - Controlling false discoveries in high-dimensional situations: boosting with
      stability selection.
AB  - BACKGROUND: Modern biotechnologies often result in high-dimensional data sets
      with many more variables than observations (n?p). These data sets pose new
      challenges to statistical analysis: Variable selection becomes one of the most
      important tasks in this setting. Similar challenges arise if in modern data sets
      from observational studies, e.g., in ecology, where flexible, non-linear models
      are fitted to high-dimensional data. We assess the recently proposed flexible
      framework for variable selection called stability selection. By the use of
      resampling procedures, stability selection adds a finite sample error control to
      high-dimensional variable selection procedures such as Lasso or boosting. We
      consider the combination of boosting and stability selection and present results
      from a detailed simulation study that provide insights into the usefulness of
      this combination. The interpretation of the used error bounds is elaborated and
      insights for practical data analysis are given. RESULTS: Stability selection with
      boosting was able to detect influential predictors in high-dimensional settings
      while controlling the given error bound in various simulation scenarios. The
      dependence on various parameters such as the sample size, the number of truly
      influential variables or tuning parameters of the algorithm was investigated. The
      results were applied to investigate phenotype measurements in patients with
      autism spectrum disorders using a log-linear interaction model which was fitted
      by boosting. Stability selection identified five differentially expressed amino
      acid pathways. CONCLUSION: Stability selection is implemented in the freely
      available R package stabs (http://CRAN.R-project.org/package=stabs). It proved to
      work well in high-dimensional settings with more predictors than observations for
      both, linear and additive models. The original version of stability selection,
      which controls the per-family error rate, is quite conservative, though, this is
      much less the case for its improvement, complementary pairs stability selection.
      Nevertheless, care should be taken to appropriately specify the error bound.

PMID- 25943567
TI  - Homocysteinemia as a risk factor for atherosclerosis: a review.
AB  - Elevation in plasma homocysteine has been widely studied as an independent risk
      factor for atherosclerosis. Animal laboratory models have demonstrated rapid
      onset vascular lesions with homocysteine infusion. A large body of data indicates
      a consistent relationship between plasma homocysteine and symptomatic
      atherosclerotic disease involving the coronary, peripheral, and cerebral
      circulations. Elevated plasma homocysteine can be predictably normalized with
      oral folate in most patients. Despite the wealth of published clinical data on
      this topic, it is unknown if normalization of plasma homocysteine in patients
      with symptomatic atherosclerosis will prevent or arrest the disease process. 

PMID- 25943566
TI  - Ask about ice, then consider iron.
AB  - BACKGROUND AND PURPOSE: The study aims to review a condition defined by the
      desire to consume ice in order to satisfy an addictive-like compulsion, rather
      than for purposes of hydration or pain relief. This condition is called ice pica,
      or pagophagia. Associations between ice pica and iron deficiency, suggestions for
      clinical screening of at risk populations, and recommendations for treatment and
      follow-up care are provided. DATA SOURCES: An extensive literature review of
      original research articles, reviews, clinical practice manuscripts, and
      scientific publications on pica and pagophagia. CONCLUSIONS: A compulsion or
      craving for the consumption of ice is often overlooked in clinical practice. It
      is therefore important for clinicians to include ice pica as part of the review
      of systems for certain patient populations. Ice pica is frequently associated
      with iron deficiency, and iron supplementation is an effective therapy in most
      cases. IMPLICATIONS FOR PRACTICE: Knowledge gained from screening for ice pica
      can generate valuable patient information and lead to the diagnosis and treatment
      of iron deficiency. The populations at risk include young women and blood donors
      of either sex.

PMID- 25943568
TI  - Intracoronary Low-Dose Ionizing Irradiation (beta or gamma) for Prevention of
      Restenosis: Could It Succeed Where Pharmacotherapy Failed?
AB  - Although the precise pathogenesis of restenosis after percutaneous transluminal
      coronary angioplasty (PTCA) remains somewhat elusive, our understanding about the
      reparative phenomena at the site of dilatation has been significantly improved in
      recent years. Thus, restenosis appears to be the result of migration,
      proliferation, and excessive matrix formation by smooth muscle cells plus
      vascular wall remodeling leading to chronic recoil (constriction). Proposed
      pharmacotherapies to prevent restenosis have been ineffective in humans, in spite
      of a relative success in certain experimental animals. The rationale for low-dose
      irradiation (either beta or gamma) in order to prevent restenosis is based on the
      known ability of ionizing irradiation to arrest cell division and, therefore, to
      reduce the number of clonal progenitors in situations like angioplasty. 

PMID- 25943569
TI  - Histological and immunohistochemical characteristics of eccentric coronary artery
      lesions retrieved by atherectomy from cardiac transplant recipients.
AB  - The lesions of cardiac allograft vasculopathy are thought to be strongly related
      to an immune inflammatory process. Little is known about the biology of these
      eccentric lesions. However, transplant patients may present with focal disease.
      Coronary atherectomy provides a unique opportunity to study these clinically
      relevant lesions in surviving transplant patients. In this series we
      characterized the features of four lesions (two restenotic and two primary) from
      three cardiac transplant recipients who underwent coronary atherectomy. The
      histologic characteristics of the lesions were analyzed and immunohistochemistry
      was used to assess qualitatively the presence of specific markers of inflammation
      and the extracellular matrix component fibronectin. Histology showed cholesterol
      clefts, calcium deposits, and foam cells with low to moderate cellularity and
      moderate to high fibrosis. Interleukin (IL)-1beta was present in two lesions, but
      tumor necrosis factor (TNF)-alpha was absent. The adhesion molecules
      intercellular adhesion molecule (ICAM)-1 and vascular cellular adhesion molecule
      (VCAM)-1 and the integrins alpha5beta1 and alpha4 were present in all lesions.
      There was mild to moderate accumulation of fibronectin. Thus, atheroscleroticlike
      features were present with only low to moderate degrees of immune inflammation.
      Our findings suggest that eccentric focal plaques in cardiac allograft
      vasculopathy are less likely to be primarily related to a prominent immune
      inflammatory process and are similar to atherosclerosis. We speculate that these
      eccentric lesions that resemble atherosclerosis may be more related to the
      conventional risk factors for coronary artery disease frequently seen in this
      population. 

PMID- 25943570
TI  - Pathology of internal mammary arteries used as bypass grafts.
AB  - We describe four patients in whom internal mammary arteries used as coronary
      artery bypass grafts demonstrated pathologic changes that could affect long-term
      patency. Two grafts showed evidence of arteritis, and two showed degenerative
      changes as seen in so-called cystic medial necrosis. In one of these two cases
      intraoperative dissection of the internal mammary artery and aorta occurred.
      Aside from the rare occurrence of atherosclerosis, we have found no previous
      reports of systemic vascular disease affecting this artery. 

PMID- 25943571
TI  - Morphologic Study of Homograft Valves before and after Cryopreservation and after
      Short-Term Implantation in Patients.
AB  - Cryopreserved heart valve homografts have been implanted in patients for the past
      15 years, but controversies still exist on the survival of donor cells, matrix
      maintenance, and possible rejection by the host. Therefore a full morphologic
      study (histology, immunohistochemistry, transmission electron microscopy, and
      cuprolinic blue-TEM for glycosaminoglycans [GAG]) of short-term implanted
      uninfected grafts was done using unimplanted valves as the reference. Unimplanted
      tissues consisted of 5 fresh and 11 cryopreserved valves. Eight implants were
      recovered at reoperation [4] or autopsy [4], 4 from the right and 4 from the left
      ventricular outflow tract. The implantation time was 2 hours to 30 days. For
      unimplanted valves we found a partial preservation of the endothelium, the
      presence of dendritic Langerhans cells (Lc) and macrophages, and no significant
      damage to fibroblasts, collagen framework, and GAG pattern, except when the
      tissues had been ischemic for a long time. Explanted cusps exhibited (i) early
      disappearance of endothelium and Lc; (ii) nonspecific low-grade inflammatory cell
      infiltration, mostly of monocytoid type; (iii) viable degree of devitalization of
      fibroblasts with persistence of viable cells in some areas in most cusps; and
      (iv) fair preservation of collagen framework and GAGs. It is likely that, in view
      of the good graft preservation at implantation, humoral rejection is responsible
      for the earlier destruction of the endothelium and dendritic cells and the
      delayed devitalization of the fibroblasts and that preservation of the collagen
      framework and other intercellular matrix components (glycosaminoglycans) should
      guarantee longterm graft function. 

PMID- 25943572
TI  - Cardiomyopathy in a male with cystinosis.
AB  - Cystinosis is a lysosomal storage disease classically associated with renal
      failure, photophobia, and hypothyroidism. Multi-organ dysfunction tends to
      develop over time, a factor of increasing significance as patient survival
      improves. Herein, we describe a male patient with cystinosis who developed a
      restrictive cardiomyopathy associated with myocardial cystine deposition and an
      ap-proximately 1000-fold elevation in myocardial cystine levels. Renal failure
      necessitated a kidney transplant at age 12. At age 31, the patient was diagnosed
      with progressive cardiac failure poorly responsive to aggressive antifailure
      therapy and risk factor modification. The patient died at age 33 in hypovolemic
      shock due to a ruptured pseudoaneurysm at an old renal transplant site. 

PMID- 25943573
TI  - Neuroendocrine and viral correlates of premature immunosenescence.
AB  - Aging continuously remodels the immune system, a process known as
      immunosenescence. Here, we review evidence of premature immunosenescence in
      younger individuals under conditions of chronic psychological stress, chronic
      inflammation, or exposure to certain persistent viral infections. Chronic stress
      may accelerate various features of immunosenescence by activating key allostatic
      systems, notably the hypothalamic-pituitary-adrenal axis and increased cortisol
      levels. Chronic stress is associated with thymic involution, blunted T cell
      proliferation, increased serum proinflammatory markers, and shorter telomere
      lengths. Human cytomegalovirus (CMV) infection has been implicated in
      accelerating immunosenescence by shrinking the T cell receptor repertoire and
      causing clonal expansion of senescent CD8(+) CD28(-) T cells with a
      proinflammatory profile. These factors increase inflammation associated with
      aging, or "inflammaging," particularly as it relates to etiology of several age
      related diseases and increased mortality. Patients with rheumatoid arthritis have
      been shown to have several signatures of premature immunosenescence, including
      expansion of senescent T cells associated with cognitive impairment. We end by
      speculating that bipolar disorder can be considered as a model of accelerated
      aging because it has been associated with shortened telomeres, higher CMV IgG
      titers, and expansion of senescent and regulatory T cells. 

PMID- 25943575
TI  - The abdominal compartment syndrome: evolving concepts and future directions.

PMID- 25943574
TI  - Treatment strategies in colorectal cancer patients with initially unresectable
      liver-only metastases, a study protocol of the randomised phase 3 CAIRO5 study of
      the Dutch Colorectal Cancer Group (DCCG).
AB  - BACKGROUND: Colorectal cancer patients with unresectable liver-only metastases
      may be cured after downsizing of metastases by neoadjuvant systemic therapy.
      However, the optimal neoadjuvant induction regimen has not been defined, and the
      lack of consensus on criteria for (un)resectability complicates the
      interpretation of published results. METHODS/DESIGN: CAIRO5 is a multicentre,
      randomised, phase 3 clinical study. Colorectal cancer patients with initially
      unresectable liver-only metastases are eligible, and will not be selected for
      potential resectability. The (un)resectability status is prospectively assessed
      by a central panel consisting of at least one radiologist and three liver
      surgeons, according to predefined criteria. Tumours of included patients will be
      tested for RAS mutation status. Patients with RAS wild type tumours will be
      treated with doublet chemotherapy (FOLFOX or FOLFIRI) and randomised between the
      addition of either bevacizumab or panitumumab, and patients with RAS mutant
      tumours will be randomised between doublet chemotherapy (FOLFOX or FOLFIRI) plus
      bevacizumab or triple chemotherapy (FOLFOXIRI) plus bevacizumab. Radiological
      evaluation to assess conversion to resectability will be performed by the central
      panel, at an interval of two months. The primary study endpoint is median
      progression-free survival. Secondary endpoints are the R0/1 resection rate,
      median overall survival, response rate, toxicity, pathological response of
      resected lesions, postoperative morbidity, and correlation of baseline and follow
      up evaluation with respect to outcomes by the central panel. DISCUSSION: CAIRO5
      is a prospective multicentre trial that investigates the optimal systemic
      induction therapy for patients with initially unresectable, liver-only colorectal
      cancer metastases. TRIAL REGISTRATION: CAIRO 5 is registered at European Clinical
      Trials Database (EudraCT) (2013-005435-24). CAIRO 5 is registered at
      ClinicalTrials.gov: NCT02162563 , June 10, 2014.

PMID- 25943577
TI  - Corrigendum: doctors and numbers: an assessment of the critical risk
      interpretation test.

PMID- 25943576
TI  - Pitch processing of dynamic lexical tones in the auditory cortex is influenced by
      sensory and extrasensory processes.
AB  - The aim is to evaluate how language experience (Chinese, English) shapes
      processing of pitch contours as reflected in the amplitude of cortical pitch
      response components. Responses were elicited from three dynamic curvilinear
      nonspeech stimuli varying in pitch direction and location of peak acceleration:
      Mandarin lexical Tone 2 (rising) and Tone 4 (falling), and a flipped variant of
      Tone 2, Tone 2' (nonnative). At temporal sites (T7/T8), Chinese listeners' Na-Pb
      response amplitudes to Tones 2 and 4 were greater than those of English listeners
      in the right hemisphere only; a rightward asymmetry for Tones 2 and 4 was
      restricted to the Chinese group. In common to both Fz-to-linked T7/T8 and T7/T8
      electrode sites, the stimulus pattern (Tones 2 and 4 > Tone 2') was found in the
      Chinese group only. As reflected by Pb-Nb at Fz, Chinese subjects' amplitudes
      were larger than those of English subjects in response to Tones 2 and 4, and
      Tones 2 and 4 were larger than Tone 2', whereas for English subjects, Tone 2 was
      larger than Tone 2' and Tone 4. At frontal electrode sites (F3/F4), regardless of
      component or hemisphere, Chinese subjects' responses were larger in amplitude
      than those of English subjects across stimuli. For either group, responses to
      Tones 2 and 4 were larger than Tone 2'. No hemispheric asymmetry was observed at
      the frontal electrode sites. These findings demonstrate that cortical pitch
      response components are differentially modulated by experience-dependent,
      temporally distinct but functionally overlapping, weighting of sensory and
      extrasensory effects on pitch processing of lexical tones in the right temporal
      lobe and, more broadly, are consistent with a distributed hierarchical predictive
      coding process. 

PMID- 25943578
TI  - Patients or volunteers? The impact of motivation for trial participation on the
      efficacy of patient decision Aids: a secondary analysis of a Cochrane systematic
      review.
AB  - BACKGROUND: Efficacy of patient decision aids (PtDAs) may be influenced by trial
      participants' identity either as patients seeking to benefit personally from
      involvement or as volunteers supporting the research effort. AIM: To determine if
      study characteristics indicative of participants' trial identity might influence
      PtDA efficacy. METHODS: We undertook exploratory subgroup meta-analysis of the
      2011 Cochrane review of PtDAs, including trials that compared PtDA with usual
      care for treatment decisions. We extracted data on whether participants initiated
      the care pathway, setting, practitioner interactions, and 6 outcome variables
      (knowledge, risk perception, decisional conflict, feeling informed, feeling clear
      about values, and participation). The main subgroup analysis categorized trials
      as "volunteerism" or "patienthood" on the basis of whether participants initiated
      the care pathway. A supplementary subgroup analysis categorized trials on the
      basis of whether any volunteerism factors were present (participants had not
      initiated the care pathway, had attended a research setting, or had a face-to
      face interaction with a researcher). RESULTS: Twenty-nine trials were included.
      Compared with volunteerism trials, pooled effect sizes were higher in patienthood
      trials (where participants initiated the care pathway) for knowledge, decisional
      conflict, feeling informed, feeling clear, and participation. The subgroup
      difference was statistically significant for knowledge only (P = 0.03). When
      trials were compared on the basis of whether volunteerism factors were present,
      knowledge was significantly greater in patienthood trials (P < 0.001), but there
      was otherwise no consistent pattern of differences in effects across outcomes.
      CONCLUSIONS: There is a tendency toward greater PtDA efficacy in trials in which
      participants initiate the pathway of care. Knowledge acquisition appears to be
      greater in trials where participants are predominantly patients rather than
      volunteers.

PMID- 25943579
TI  - Is patients' numeracy related to physical and mental health?
AB  - OBJECTIVE: There is compelling evidence showing that health literacy influences
      health outcomes. However, there is a dearth of research investigating this issue
      in the vast literature on numeracy-the ability to accurately interpret numerical
      information about risk, a skill that is only moderately correlated with health
      literacy. In a cross-sectional study, we investigated whether objective and
      subjective numeracy is related to objective and subjective health outcomes.
      Objective (subjective) numeracy is actual (self-reported) numerical competence.
      Objective outcomes include prevalence of comorbidity and prescribed medications.
      Subjective outcomes include perceptions of physical and mental health. METHODS: A
      convenience sample of 502 male individuals receiving outpatient care at a
      Veterans Affairs Medical Center reported their demographics and answered a survey
      measuring objective and subjective numeracy, trust in physicians, satisfaction
      with role in medical decision making, perceptions of physical and mental health,
      and risky habits. We computed patients' body mass index (BMI) and their age
      adjusted Charlson index-an extensively studied comorbidity index for predicting
      mortality in clinical research. We retrieved number of prescribed medications
      from medical records. RESULTS: Compared with patients who had high objective
      numeracy, patients with low objective numeracy showed higher prevalence of
      comorbidities and took more prescribed medications. Compared with patients who
      had high subjective numeracy, patients with low subjective numeracy had more
      negative perceptions of their physical and mental health. These conclusions held
      after controlling for the effect of demographics, risky habits, BMI, trust in
      physicians, and satisfaction with role in decision making, suggesting that
      numeracy has a unique, significant contribution to health outcomes beyond the
      effect of these factors. CONCLUSIONS: Our research documents for the first time
      that self-reported numeracy is related to perceptions of health, whereas
      objective numeracy is related to actual health, laying the groundwork for future
      research on the effect of numeracy on health outcomes.

PMID- 25943580
TI  - Prevalence of the F-type lectin domain.
AB  - F-type lectins are fucolectins with characteristic fucose and calcium-binding
      sequence motifs and a unique lectin fold (the "F-type" fold). F-type lectins are
      phylogenetically widespread with selective distribution. Several eukaryotic F
      type lectins have been biochemically and structurally characterized, and the F
      type lectin domain (FLD) has also been studied in the bacterial proteins,
      Streptococcus mitis lectinolysin and Streptococcus pneumoniae SP2159. However,
      there is little knowledge about the extent of occurrence of FLDs and their domain
      organization, especially, in bacteria. We have now mined the extensive genomic
      sequence information available in the public databases with sensitive sequence
      search techniques in order to exhaustively survey prokaryotic and eukaryotic
      FLDs. We report 437 FLD sequence clusters (clustered at 80% sequence identity)
      from eukaryotic, eubacterial and viral proteins. Domain architectures are diverse
      but mostly conserved in closely related organisms, and domain organizations of
      bacterial FLD-containing proteins are very different from their eukaryotic
      counterparts, suggesting unique specialization of FLDs to suit different
      requirements. Several atypical phylogenetic associations hint at lateral
      transfer. Among eukaryotes, we observe an expansion of FLDs in terms of
      occurrence and domain organization diversity in the taxa Mollusca, Hemichordata
      and Branchiostomi, perhaps coinciding with greater emphasis on innate immune
      strategies in these organisms. The naturally occurring FLDs with diverse domain
      organizations that we have identified here will be useful for future studies
      aimed at creating designer molecular platforms for directing desired biological
      activities to fucosylated glycoconjugates in target niches. 

PMID- 25943581
TI  - Informed consent: the dawning of a new era.

PMID- 25943582
TI  - Improved recovery of Listeria monocytogenes from stainless steel and
      polytetrafluoroethylene surfaces using air/water ablation.
AB  - AIMS: To develop a gentle ablation technique to recover Listeria monocytogenes
      biofilms from stainless steel (SS) and polytetrafluoroethylene (PTFE) surfaces by
      using compressed air and water injection. METHODS AND RESULTS: Biofilms were
      grown for 4, 24 and 48 h or 7 days and a compressed air and water flow at 2, 3
      and 4 bars was applied for cell removal. Collected cells were quantified for
      total/dead by staining with SYTO 9/PI double staining and cultivable populations
      were determined by plating onto brain heart infusion (BHI) agar, while coupon
      surfaces also were stained with DAPI to quantify in situ the remaining cells. The
      recovery efficiency was compared to that of conventional swabbing. Results showed
      that the air/water ablation is able to collect up to 98.6% of cells from SS
      surfaces while swabbing only recovered 11.2% of biofilm. Moreover, air/water
      ablation recovered 99.9% of cells from PTFE surfaces. CONCLUSIONS: The high
      recovery rate achieved by this technique, along with the fact that cells were
      able to retain membrane integrity and cultivability, indicate that this device is
      suitable for the gentle recovery of viable L. monocytogenes biofilm cells.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This work presents a highly efficient
      technique to remove, collect and quantify L. monocytogenes from surfaces commonly
      used in the food industry, which can thus serve as an important aid in verifying
      cleaning and sanitation as well as in reducing the likelihood of cross
      contamination events.

PMID- 25943584
TI  - A combination of alfaxalone and medetomidine followed by an alfaxalone continuous
      rate infusion in cynomolgus monkeys (Macaca fascicularis) undergoing pharmacoMRS.

PMID- 25943583
TI  - Clock genes * stress * reward interactions in alcohol and substance use
      disorders.
AB  - Adverse life events and highly stressful environments have deleterious
      consequences for mental health. Those environmental factors can potentiate
      alcohol and drug abuse in vulnerable individuals carrying specific genetic risk
      factors, hence producing the final risk for alcohol- and substance-use disorders
      development. The nature of these genes remains to be fully determined, but
      studies indicate their direct or indirect relation to the stress hypothalamo
      pituitary-adrenal (HPA) axis and/or reward systems. Over the past decade, clock
      genes have been revealed to be key-players in influencing acute and chronic
      alcohol/drug effects. In parallel, the influence of chronic stress and stressful
      life events in promoting alcohol and substance use and abuse has been
      demonstrated. Furthermore, the reciprocal interaction of clock genes with various
      HPA-axis components, as well as the evidence for an implication of clock genes in
      stress-induced alcohol abuse, have led to the idea that clock genes, and Period
      genes in particular, may represent key genetic factors to consider when examining
      gene * environment interaction in the etiology of addiction. The aim of the
      present review is to summarize findings linking clock genes, stress, and alcohol
      and substance abuse, and to propose potential underlying neurobiological
      mechanisms.

PMID- 25943586
TI  - A paradigm shift in pharmacokinetic-pharmacodynamic (PKPD) modeling: rule of
      thumb for estimating free drug level in tissue compared with plasma to guide drug
      design.
AB  - A basic assumption in pharmacokinetics-pharmacodynamics research is that the free
      drug concentration is similar in plasma and tissue, and, hence, in vitro plasma
      data can be used to estimate the in vivo condition in tissue. However, in a
      companion manuscript, it has been demonstrated that this assumption is violated
      for the ionized drugs. Nonetheless, these observations focus on in vitro static
      environments and do not challenge data with an in vivo dynamic system. Therefore,
      an extension from an in vitro to an in vivo system becomes the necessary next
      step. The objective of this study was to perform theoretical simulations of the
      free drug concentration in tissue and plasma by using a physiologically based
      pharmacokinetics (PBPK) model reproducing the in vivo conditions in human.
      Therefore, the effects of drug ionization, lipophilicity, and clearance have been
      taken into account in a dynamic system. This modeling exercise was performed as a
      proof of concept to demonstrate that free drug concentration in tissue and plasma
      may also differ in a dynamic system for passively permeable drugs that are
      ionized at the physiological pH. The PBPK model simulations indicated that free
      drug concentrations in tissue cells and plasma significantly differ for the
      ionized drugs because of the pH gradient effect between cells and interstitial
      space. Hence, a rule of thumb for potentially performing more accurate PBPK/PD
      modeling is suggested, which states that the free drug concentration in tissue
      and plasma will differ for the ionizable drugs in contrast to the neutral drugs.
      In addition to the pH gradient effect for the ionizable drugs, lipophilicity and
      clearance effects will increase or decrease the free drug concentration in tissue
      and plasma for each class of drugs; thus, higher will be the drug lipophilicity
      and clearance, lower would be the free drug concentration in plasma, and, hence,
      in tissue, in a dynamic in vivo system. Therefore, only considering the value of
      free fraction in plasma derived from a static in vitro environment might be
      biased to guide drug design (the old paradigm), and, hence, it is recommended to
      use a PBPK model to reproduce more accurately the in vivo condition in tissue
      (the new paradigm). This newly developed approach can be used to predict free
      drug concentration in diverse tissue compartments for small molecules in
      toxicology and pharmacology studies, which can be leveraged to optimize the
      pharmacokinetics drivers of tissue distribution based upon physicochemical and
      physiological input parameters in an attempt to optimize free drug level in
      tissue. Overall, this present study provides guidance on the application of
      plasma and tissue concentration information in PBPK/PD research in preclinical
      and clinical studies, which is in accordance with the recent literature.

PMID- 25943585
TI  - Modeling early-onset post-ischemic seizures in aging mice.
AB  - Stroke is the leading cause of seizures and epilepsy in the aged population, with
      post-stroke seizures being a poor prognostic factor. The pathological processes
      underlying post-stroke seizures are not well understood and studies of these
      seizures in aging/aged animals remain scarce. Therefore, our primary objective
      was to model post-stroke seizures in aging mice (C57 black strain, 16-20 months
      old), with a focus on early-onset, convulsive seizures that occur within 24-hours
      of brain ischemia. We utilized a middle cerebral artery occlusion model and
      examined seizure activity and brain injury using combined behavioral and
      electroencephalographic monitoring and histological assessments. Aging mice
      exhibited vigorous convulsive seizures within hours of the middle cerebral artery
      occlusion. These seizures manifested with jumping, rapid running, barrel-rolling
      and/or falling all in the absence of hippocampal-cortical electrographic
      discharges. Seizure development was closely associated with severe brain injury
      and acute mortality. Anticonvulsive treatments after seizure occurrence offered
      temporary seizure control but failed to improve animal survival. A separate
      cohort of adult mice (6-8 months-old) exhibited analogous early-onset convulsive
      seizures following the middle cerebral artery occlusion but had better survival
      outcomes following anticonvulsive treatment. Collectively, our data suggest that
      early-onset convulsive seizures are a result of severe brain ischemia in aging
      animals.

PMID- 25943587
TI  - Outbreak of Influenza A(H1N1) in a Kidney Transplant Unit-Protective Effect of
      Vaccination.
AB  - Seasonal influenza vaccination is recommended for patients with end-stage renal
      disease (ESRD), despite suggested inferior efficacy among these patients. We
      characterize an outbreak of influenza A(H1N1) in a kidney transplant unit.
      Altogether 23 patients were treated on the ward for postoperative care after
      kidney transplantation during the outbreak. After the first positive case, all
      patients were tested with nasopharyngeal swab tests and 7 patients were diagnosed
      with influenza A(H1N1). Altogether 17/23 patients had received adequate seasonal
      influenza vaccination, of whom 2/17 tested positive for influenza (one
      asymptomatic, one with mild cough). Five of six unvaccinated patients were
      diagnosed with influenza A(H1N1); 3/5 suffered from severe respiratory failure
      and were treated with ventilator support in the ICU, but all died due to acute
      respiratory distress syndrome, whereas 2/5 suffered from mild viral pneumonitis
      and recovered fully. The risk of influenza infection and mortality was
      significantly increased in unvaccinated patients (odds ratio 37.5 [95% CI 2.7
      507.5, p = 0.01] and 6.7 [95% CI 2.3-18.9, p = 0.003], respectively). Influenza
      A(H1N1) had a high mortality in our cohort of nonvaccinated immunosuppressed
      patients early after kidney transplantation. None of the vaccinated patients
      developed serious disease, supporting the role of vaccination also for ESRD
      patients. 

PMID- 25943588
TI  - Fractalkine neutralization improves cardiac function after myocardial infarction.
AB  - NEW FINDINGS: What is the central question of this study? What is the
      cardioprotective role of fractalkine neutralization in heart failure and what are
      the mechanisms responsible? What is the main finding and its importance? The
      concentration of fractalkine is increased in the left ventricle of mice with
      myocardial infarction, similar to the increases in plasma from heart failure
      patients. The present study shows a clear beneficial effect of neutralizing
      fractalkine in a model of myocardial infarction, which results in increased
      survival. Such an approach may be worthwhile in human patients. Concentrations of
      the chemokine fractalkine (FKN) are increased in patients with chronic heart
      failure, and our previous studies show that aged mice lacking the prostaglandin
      E2 EP4 receptor subtype (EP4-KO) have increased cardiac FKN, with a phenotype of
      dilated cardiomyopathy. However, how FKN participates in the pathogenesis of
      heart failure has rarely been studied. We hypothesized that FKN contributes to
      the pathogenesis of heart failure and that anti-FKN treatment prevents heart
      failure induced by myocardial infarction (MI) more effectively in EP4-KO mice.
      Male EP4-KO mice and wild-type littermates underwent sham or MI surgery and were
      treated with an anti-FKN antibody or control IgG. At 2 weeks post-MI,
      echocardiography was performed and hearts were excised for determination of
      infarct size, immunohistochemistry and Western blot of signalling molecules.
      Given that FKN protein levels in the left ventricle were increased to a similar
      extent in both strains after MI and that anti-FKN treatment improved survival and
      cardiac function in both strains, we subsequently used only wild-type mice to
      examine the mechanisms whereby anti-FKN is cardioprotective. Myocyte cross
      sectional area and interstitial collagen fraction were reduced after anti-FKN
      treatment, as were macrophage migration and gelatinase activity. Activation of
      ERK1/2 and p38 MAPK were reduced after neutralization of FKN. In vitro, FKN
      increased fibroblast proliferation. In conclusion, increased FKN contributes to
      heart failure after MI. This effect is not exacerbated in EP4-KO mice, suggesting
      that there is no link between FKN and lack of EP4. Overall, inhibition of FKN may
      be important to preserve cardiac function post-MI.

PMID- 25943589
TI  - Critique of a systematic review and meta-analysis of premature mortality in
      bipolar affective disorder.

PMID- 25943591
TI  - Remembering Dr. Carlos Salinas.

PMID- 25943590
TI  - Smartphone apps for calculating insulin dose: a systematic assessment.
AB  - BACKGROUND: Medical apps are widely available, increasingly used by patients and
      clinicians, and are being actively promoted for use in routine care. However,
      there is little systematic evidence exploring possible risks associated with apps
      intended for patient use. Because self-medication errors are a recognized source
      of avoidable harm, apps that affect medication use, such as dose calculators,
      deserve particular scrutiny. We explored the accuracy and clinical suitability of
      apps for calculating medication doses, focusing on insulin calculators for
      patients with diabetes as a representative use for a prevalent long-term
      condition. METHODS: We performed a systematic assessment of all English-language
      rapid/short-acting insulin dose calculators available for iOS and Android.
      RESULTS: Searches identified 46 calculators that performed simple mathematical
      operations using planned carbohydrate intake and measured blood glucose. While
      59% (n = 27/46) of apps included a clinical disclaimer, only 30% (n = 14/46)
      documented the calculation formula. 91% (n = 42/46) lacked numeric input
      validation, 59% (n = 27/46) allowed calculation when one or more values were
      missing, 48% (n = 22/46) used ambiguous terminology, 9% (n = 4/46) did not use
      adequate numeric precision and 4% (n = 2/46) did not store parameters faithfully.
      67% (n = 31/46) of apps carried a risk of inappropriate output dose
      recommendation that either violated basic clinical assumptions (48%, n = 22/46)
      or did not match a stated formula (14%, n = 3/21) or correctly update in response
      to changing user inputs (37%, n = 17/46). Only one app, for iOS, was issue-free
      according to our criteria. No significant differences were observed in issue
      prevalence by payment model or platform. CONCLUSIONS: The majority of insulin
      dose calculator apps provide no protection against, and may actively contribute
      to, incorrect or inappropriate dose recommendations that put current users at
      risk of both catastrophic overdose and more subtle harms resulting from
      suboptimal glucose control. Healthcare professionals should exercise substantial
      caution in recommending unregulated dose calculators to patients and address app
      safety as part of self-management education. The prevalence of errors
      attributable to incorrect interpretation of medical principles underlines the
      importance of clinical input during app design. Systemic issues affecting the
      safety and suitability of higher-risk apps may require coordinated surveillance
      and action at national and international levels involving regulators, health
      agencies and app stores.

PMID- 25943592
TI  - Morphological and molecular characterization of separated pelagic eggs from
      Lophius litulon (Lophiiformes; Lophiidae).
AB  - Free-floating eggs of Lophius litulon were collected using plankton nets after
      their release from a pelagic egg mass. The eggs were identified based on
      molecular analysis and several morphological characteristics. These rare,
      separated eggs have not been reported previously and represent the first such
      finding for Lophiiformes. 

PMID- 25943593
TI  - To what extent does sociodemographic composition of the neighbourhood explain
      regional differences in demand of primary out-of-hours care: a multilevel study.
AB  - BACKGROUND: In the Netherlands, primary out-of-hours (OOH) care is provided by
      large scale General Practitioner (GP) cooperatives. GP cooperatives can be
      contacted by patients living in the area surrounding the GP cooperative
      (catchment area) at hours when the patient's own general practice is closed. The
      frequency of primary OOH care use substantially differs between GP cooperative
      catchment areas. To enable a better match between supply and demand of OOH
      services, understanding of the factors associated with primary OOH care use is
      essential. The present study evaluated the contribution of sociodemographic
      composition of the neighbourhood in explaining differences in primary OOH care
      use between GP cooperative catchment areas. METHODS: Data about patients'
      contacts with primary OOH services (n = 1,668,047) were derived from routine
      electronic health records of 21 GP cooperatives participating in the NIVEL
      Primary Care Database in 2012. The study sample is representative for the Dutch
      population (for age and gender). Data were matched with sociodemographic
      characteristics (e.g. gender, age, low-income status, degree of urbanisation) on
      postcode level. Multilevel linear regression models included postcode level
      (first level), nested within GP cooperative catchment areas (second level). We
      investigated whether contacts in primary OOH care were associated with
      neighbourhood sociodemographic characteristics. RESULTS: The demand of primary
      OOH care was significantly higher in neighbourhoods with more women, low-income
      households, non-Western immigrants, neighbourhoods with a higher degree of
      urbanisation, and low neighbourhood socioeconomic status. Conversely, lower
      demand was associated with neighbourhoods with more 5 to 24 year old inhabitants.
      Sociodemographic neighbourhood characteristics explained a large part of the
      variation between GP cooperatives (R-squared ranging from 8% to 52%).
      Nevertheless, the multilevel models also showed that a considerable amount of
      variation in demand between GP cooperatives remained unexplained by
      sociodemographic characteristics, particularly regarding high-urgency contacts.
      CONCLUSIONS: Although part of the variation between GP cooperatives could not be
      attributed to neighbourhood characteristics, the sociodemographic composition of
      the neighbourhood is a fair predictor of the demand of primary OOH care.
      Accordingly, this study provides a useful starting point for an improved planning
      of the supply of primary OOH care.

PMID- 25943595
TI  - Biocompatibility of single-walled carbon nanotube composites for bone
      regeneration.
AB  - OBJECTIVES: The purpose of this study was to evaluate in vivo biocompatibility of
      novel single-walled carbon nanotubes (SWCNT)/poly(lactic-co-glycolic acid)
      (PLAGA) composites for applications in bone and tissue regeneration. METHODS: A
      total of 60 Sprague-Dawley rats (125 g to 149 g) were implanted subcutaneously
      with SWCNT/PLAGA composites (10 mg SWCNT and 1gm PLAGA 12 mm diameter two
      dimensional disks), and at two, four, eight and 12 weeks post-implantation were
      compared with control (Sham) and PLAGA (five rats per group/point in time). Rats
      were observed for signs of morbidity, overt toxicity, weight gain and food
      consumption, while haematology, urinalysis and histopathology were completed when
      the animals were killed. RESULTS: No mortality and clinical signs were observed.
      All groups showed consistent weight gain, and the rate of gain for each group was
      similar. All groups exhibited a similar pattern for food consumption. No
      difference in urinalysis, haematology, and absolute and relative organ weight was
      observed. A mild to moderate increase in the summary toxicity (sumtox) score was
      observed for PLAGA and SWCNT/PLAGA implanted animals, whereas the control animals
      did not show any response. Both PLAGA and SWCNT/PLAGA showed a significantly
      higher sumtox score compared with the control group at all time intervals.
      However, there was no significant difference between PLAGA and SWCNT/PLAGA
      groups. CONCLUSIONS: Our results demonstrate that SWCNT/PLAGA composites
      exhibited in vivo biocompatibility similar to the Food and Drug Administration
      approved biocompatible polymer, PLAGA, over a period of 12 weeks. These results
      showed potential of SWCNT/PLAGA composites for bone regeneration as the low
      percentage of SWCNT did not elicit a localised or general overt toxicity.
      Following the 12-week exposure, the material was considered to have an acceptable
      biocompatibility to warrant further long-term and more invasive in vivo studies.
      Cite this article: Bone Joint Res 2015;4:70-7.

PMID- 25943594
TI  - Multi-layered epigenetic mechanisms contribute to transcriptional memory in T
      lymphocytes.
AB  - BACKGROUND: Immunological memory is the ability of the immune system to respond
      more rapidly and effectively to previously encountered pathogens, a key feature
      of adaptive immunity. The capacity of memory T cells to "remember" previous
      cellular responses to specific antigens ultimately resides in their unique
      patterns of gene expression. Following re-exposure to an antigen, previously
      activated genes are transcribed more rapidly and robustly in memory T cells
      compared to their naive counterparts. The ability for cells to remember past
      transcriptional responses is termed "adaptive transcriptional memory". RESULTS:
      Recent global epigenome studies suggest that epigenetic mechanisms are central to
      establishing and maintaining transcriptional memory, with elegant studies in
      model organisms providing tantalizing insights into the epigenetic programs that
      contribute to adaptive immunity. These epigenetic mechanisms are diverse, and
      include not only classical acetylation and methylation events, but also exciting
      and less well-known mechanisms involving histone structure, upstream signalling
      pathways, and nuclear localisation of genomic regions. CONCLUSIONS: Current
      global health challenges in areas such as tuberculosis and influenza demand not
      only more effective and safer vaccines, but also vaccines for a wider range of
      health priorities, including HIV, cancer, and emerging pathogens such as Ebola.
      Understanding the multi-layered epigenetic mechanisms that underpin the rapid
      recall responses of memory T cells following reactivation is a critical component
      of this development pathway.

PMID- 25943596
TI  - Projected Clinical, Resource Use, and Fiscal Impacts of Implementing Low-Dose
      Computed Tomography Lung Cancer Screening in Medicare.
AB  - PURPOSE: The Centers for Medicare and Medicaid Services (CMS) recently issued a
      national coverage determination that provides reimbursement for low-dose computed
      tomography (CT) lung cancer screening for enrollees age 55 to 77 years with >= 30
      pack-year smoking history who currently smoke or quit in the last 15 years. The
      clinical, resource use, and fiscal impacts of this change in screening coverage
      policy remain uncertain. METHODS: We developed a simulation model to forecast the
      5-year health outcome impacts of the CMS low-dose CT screening policy in Medicare
      compared with no screening. The model used data from the National Lung Screening
      Trial, CMS enrollment statistics and reimbursement schedules, and peer-reviewed
      literature. Outcomes included counts of screening examinations, patient cases of
      lung cancer detected, stage distribution, and total and per-enrollee per-month
      fiscal impact. RESULTS: Over 5 years, we project that low-dose CT screening will
      result in 10.7 million more low-dose CT scans, 52,000 more lung cancers detected,
      and increased overall expenditure of $6.8 billion ($2.22 per Medicare enrollee
      per month). The most fiscally impactful factors were the average cost-per
      screening episode, proportion of enrollees eligible for screening, and cost of
      treating stage I lung cancer. CONCLUSION: Low-dose CT screening is expected to
      increase lung cancer diagnoses, shift stage at diagnosis toward earlier stages,
      and substantially increase Medicare expenditures over a 5-year time horizon.
      These projections can inform planning efforts by Medicare administrators,
      contracted health care providers, and other stakeholders.

PMID- 25943597
TI  - Looking to the future: predicting renal replacement outcomes in a large community
      cohort with chronic kidney disease.
AB  - BACKGROUND: Chronic kidney disease (CKD) is common and important due to poor
      outcomes. An ability to stratify CKD care based on outcome risk should improve
      care for all. Our objective was to develop and validate 5-year outcome prediction
      tools in a large population-based CKD cohort. Model performance was compared with
      the recently reported 'kidney failure risk equation' (KFRE) models. METHODS:
      Those with CKD in the Grampian Laboratory Outcomes Mortality and Morbidity Study
      I (3396) and -II (18 687) cohorts were used to develop and validate a renal
      replacement therapy (RRT) prediction tool. The discrimination, calibration and
      overall performance were assessed. The net reclassification index compared
      performance of the developed model and the 3- and 4-variable KFRE model to
      predict RRT in the validation cohort. RESULTS: The developed model (with measures
      of age, sex, excretory renal function and proteinuria) performed well with a C
      statistic of 0.938 (0.918-0.957) and Hosmer-Lemeshow (HL) chi(2) statistic 4.6.
      In the validation cohort (18 687), the developed model falsely identified fewer
      as high risk (414 versus 3278 individuals) compared with the KFRE 3-variable
      model (measures of age, sex and excretory renal function), but had more false
      negatives (58 versus 21 individuals). The KFRE 4-variable model could only be
      applied to 2274 individuals because of a lack of baseline urinary albumin
      creatinine ratio data, thus limiting its use in routine clinical practice.
      CONCLUSIONS: CKD outcome prediction tools have been developed by ourselves and
      others. These tools could be used to stratify care, but identify both false
      positives and -negatives. Further refinement should optimize the balance between
      identifying those at increased risk with clinical utility for stratifying care.

PMID- 25943598
TI  - Risk factors for foot ulceration and lower extremity amputation in adults with
      end-stage renal disease on dialysis: a systematic review and meta-analysis.
AB  - BACKGROUND: Adults with end-stage renal disease are at increased risk of foot
      ulceration and lower extremity amputation. However, the central determinants of
      lower limb injury and loss are incompletely understood. METHODS: We conducted a
      systematic review of non-randomized studies that quantified the major risk
      factors for foot ulceration and amputation in adults treated with dialysis and
      analysed patient populations in which risks were greatest. Random-effects meta
      analysis was used to generate summary estimates. RESULTS: Thirty studies (48 566
      participants) were identified. Risk factors for foot ulceration and amputation
      included previous foot ulceration (odds ratios, OR, 17.56 and 70.13), peripheral
      arterial disease (OR, 7.52 and 9.12), diabetes (OR, 3.76 and 7.48), peripheral
      neuropathy (OR, 3.24 and 3.36) and coronary artery disease (OR, 3.92 and 2.49).
      Participants with foot ulceration or amputation had experienced a longer duration
      of diabetes (mean difference, MD, 4.04 and 6.07 years) and had lower serum
      albumin levels (MD, -0.23 and -0.13 g/dL). Risk factors for foot ulceration also
      included retinopathy (OR, 3.03), previous amputation (OR, 15.50) and higher serum
      phosphorus levels (MD, 0.40 mg/dL), while risk factors for amputation also
      included male sex (OR, 1.50), current smoking (OR, 2.26) and higher glycated
      haemoglobin levels (MD, 0.75%). CONCLUSIONS: Dialysis patients who have markedly
      higher risks of ulceration or amputation include those with previous foot
      ulceration or amputation, peripheral neuropathy, diabetes or macrovascular
      disease. The temporal relationship between these risk factors and the development
      of foot ulceration and/or limb loss is uncertain and requires further study.
      Stable estimates of the key risk factors for ulceration and amputation can inform
      the design of future trials investigating clinical interventions to reduce the
      burden of lower limb disease in the dialysis population.

PMID- 25943599
TI  - The development of laryngoscope blades for more challenging situations.

PMID- 25943600
TI  - Research subjects' voices: the missing element in research ethics.

PMID- 25943601
TI  - Debriefing after simulation-based non-technical skill training in healthcare: a
      systematic review of effective practice.
AB  - Non-technical skills training in healthcare frequently uses high-fidelity
      simulation followed by a facilitated discussion known as debriefing. This type of
      training is mandatory for anaesthesia training in Australia and New Zealand.
      Debriefing by a skilled facilitator is thought to be essential for new learning
      through feedback and reflective processes. Key elements of effective debriefing
      need to be clearly identified to ensure that the training is evidence-based. We
      undertook a systematic review of empirical studies where elements of debriefing
      have been systematically manipulated during non-technical skills training. Eight
      publications met the inclusion criteria, but seven of these were of limited
      generalisability. The only study that was generalisable found that debriefing by
      novice instructors using a script improved team leader performance in paediatric
      resuscitation. The remaining seven publications were limited by the small number
      of debriefers included in each study and these reports were thus analogous to
      case reports. Generally, performance improved after debriefing by a skilled
      facilitator. However, the debriefer provided no specific advantage over other
      post-experience educational interventions. Acknowledging their limitations, these
      studies found that performance improved after self-led debrief, no debrief (with
      experienced practitioners), standardised multimedia debrief or after reviewing a
      DVD of the participants' own eye-tracking. There was no added performance
      improvement when review of a video recording was added to facilitator-led
      debriefing. One study reported no performance improvement after debriefing.
      Without empirical evidence that is specific to the healthcare domain, theories of
      learning from education and psychology should continue to inform practices and
      teaching for effective debriefing. 

PMID- 25943602
TI  - Intensive care unit research ethics and trials on unconscious patients.
AB  - There are widely acknowledged ethical issues in enrolling unconscious patients in
      research trials, particularly in intensive care unit (ICU) settings. An analysis
      of those issues shows that, by and large, patients are better served in units
      where research is actively taking place for several reasons: i) they do not fall
      prey to therapeutic prejudices without clear evidential support, ii) they get a
      chance of accessing new and potentially beneficial treatments, iii) a climate of
      careful monitoring of patients and their clinical progress is necessary for good
      clinical research and affects the care of all patients and iv) even those not in
      the treatment arm of a trial of a new intervention must receive best current
      standard care (according to international evidence-based treatment guidelines).
      Given that we have discovered a number of 'best practice' regimens of care that
      do not optimise outcomes in ICU settings, it is of great benefit to all patients
      (including those participating in research) that we are constantly updating and
      evaluating what we do. Therefore, the practice of ICU-based clinical research on
      patients, many of whom cannot give prospective informed consent, ticks all the
      ethical boxes and ought to be encouraged in our health system. It is very
      important that the evaluation of protocols for ICU research should not overlook
      obvious (albeit probabilistic) benefits to patients and the acceptability of
      responsible clinicians entering patients into well-designed trials, even though
      the ICU setting does not and cannot conform to typical informed consent
      procedures and requirements. 

PMID- 25943603
TI  - Research without informed patient consent in incompetent patients.
AB  - Most patients needing intensive care cannot give informed consent to
      participation in research. This includes the most acutely and severely ill, with
      the highest mortality and morbidity where research has the greatest potential to
      improve patient outcomes. In these circumstances consent is usually sought from a
      substitute decision maker, but while survivors of intensive care believe
      substitute decision makers will look after their interests, evidence suggests
      substitute decision makers are poorly equipped for this task. Various models have
      been suggested for research without patient informed consent when intervention is
      urgent and cannot wait until first person consent is possible, including a waiver
      of consent if conditions are met. A nationally consistent model is proposed for
      Australia with a robust process for initial waiver of consent followed by first
      person consent to further research-related procedures or ongoing follow-up when
      this can be competently provided. 

PMID- 25943604
TI  - Predictors of an increased in vitro thrombotic and bleeding tendency in
      critically ill trauma and non-trauma patients.
AB  - Trauma patients are at a high risk of both bleeding and thromboembolism. This
      study assessed whether conventional coagulation blood tests were reliable
      predictors of an increased in vitro thrombotic and bleeding tendency of trauma
      and non-trauma patients. Conventional coagulation blood tests and
      thromboelastographs of 63 trauma and 63 randomly selected, critically ill non
      trauma patients were compared. Increased in vitro thrombotic and bleeding
      tendencies were defined by a maximum amplitude>72 mm or an angle>74 degrees  on
      the thromboelastograph and a maximum amplitude<54 mm or an angle<47 degrees ,
      respectively. In vitro thrombotic tendency was more common than bleeding tendency
      and this was not different between the critically ill trauma and non-trauma
      patients (59% versus 67% with thrombotic tendency, P=0.461; 11% versus 10% with
      bleeding tendency, respectively, P=0.999). Thrombocytopenia (<150x10(9)/l) and
      low fibrinogen concentrations (<2 g/l) were the only two factors associated with
      an increased in vitro bleeding tendency (both P=0.001) and thrombocytopenia was
      the only factor associated with a lower risk of in vitro thrombotic tendency (21%
      versus 75%, P=0.001). Platelet counts (Pearson's correlation coefficient [r]:
      0.59, P=0.001) and fibrinogen concentrations (r 0.61, P=0.001) both had a
      relatively linear association with maximum amplitude of the thromboelastograph.
      Prolonged International Normalized Ratio (>1.5) and activated Partial
      Thromboplastin Time (>40 seconds) were, however, not significantly associated
      with an increased in vitro thrombotic or bleeding tendency. In conclusion, in
      vitro thrombotic tendency was more common than bleeding tendency in critically
      ill trauma and non-trauma patients. Platelet counts and fibrinogen concentrations
      were better predictors of increased in vitro thrombotic and bleeding risks than
      International Normalized Ratio or activated Partial Thromboplastin Time.

PMID- 25943605
TI  - Consent for labour epidural analgesia: an observational study in a single
      institution.
AB  - There is a wide range of practice amongst obstetric anaesthetists when obtaining
      consent for women requesting labour epidural analgesia. This is the first
      prospective observational study recording the number and types of risks mentioned
      and whether the risk was quantified. Statements of benefits and alternatives to
      the procedure were also noted. Fourteen anaesthetists, each consulting a single
      patient, were recorded during the process of obtaining consent and inserting the
      epidural. The most commonly mentioned risks (median 7) were headache/dural
      puncture, failure/difficulty with insertion, nerve damage, bleeding/haematoma and
      infection/epidural abscess. There was no difference between consultants and
      trainees, although consultants showed greater variance. It was uncommon for
      anaesthetists to state a benefit (21%) or mention an alternative option (21%),
      but there was usually a quantitative statement of risk (71%). Data showed a
      deviation from the Australian and New Zealand College of Anaesthetists guidelines
      and these findings may encourage anaesthetists to reflect on their own practice
      and guide future research. 

PMID- 25943606
TI  - The teaching portfolio as a professional development tool for anaesthetists.
AB  - A teaching portfolio (TP) is a document containing a factual description of a
      teacher's teaching strengths and accomplishments, allowing clinicians to display
      them for examination by others. The primary aim of a TP is to improve quality of
      teaching by providing a structure for self-reflection, which in turn aids
      professional development in medical education. Contents typically include a
      personal statement on teaching, an overview of teaching accomplishments and
      activities, feedback from colleagues and learners, a reflective component and
      some examples of teaching material. Electronic portfolios are more portable and
      flexible compared to paper portfolios. Clinicians gain the most benefit from a TP
      when it is used as a tool for self-reflection of their teaching practice and not
      merely as a list of activities and achievements. This article explains why and
      how anaesthetists might use a TP as a tool for professional development in
      medical education. 

PMID- 25943607
TI  - Protocolised approach to end-of-life care in the ICU--the ICU PALCare Pilot
      Project.
AB  - International literature on end-of-life care in intensive care units (ICUs)
      supports the use of 'protocol bundles', which is not common practice in our 18
      bed adult general ICU in Sydney, New South Wales. We conducted a prospective
      observational study to identify problems related to end-of-life care practices
      and to determine whether there was a need to develop protocol bundles. Any ICU
      patient who had 'withdrawal' of life-sustaining treatment to facilitate a
      comfortable death was eligible. Exclusion criteria included organ donors,
      unsuitable family dynamics and lack of availability of research staff to obtain
      family consent. Process-of-care measures were collected using a standardised
      form. Satisfaction ratings were obtained using de-identified questionnaire
      surveys given to the healthcare staff shortly after the withdrawal of therapy and
      to the families 30 days later. Twenty-three patients were enrolled between June
      2011 and July 2012. Survey questionnaires were given to 25 family members and 30
      healthcare staff, with a high completion rate (24 family members [96%] and 28
      staff [93.3%]). Problems identified included poor documentation of family
      meetings (39%) and symptom management. Emotional/spiritual support was not
      offered to families (39.1%) or ICU staff (0%). The overall level of end-of-life
      care was good. The overwhelming majority of families and healthcare staff were
      highly satisfied with the care provided. Problems identified related to
      communication documentation and lack of spiritual/emotional support. To address
      these problems, targeted measures would be more useful than the adoption of
      protocol bundles. Alternate models of satisfaction surveys may be needed. 

PMID- 25943608
TI  - Systematic review and meta-analysis of method comparison studies of Masimo pulse
      co-oximeters (Radical-7TM or Pronto-7TM) and HemoCue(r) absorption spectrometers
      (B-Hemoglobin or 201+) with laboratory haemoglobin estimation.
AB  - We assessed agreement in haemoglobin measurement between Masimo pulse co
      oximeters (Rad-7TM and Pronto-7TM) and HemoCue(r) photometers (201+ or B
      Hemoglobin) with laboratory-based determination and identified 39 relevant
      studies (2915 patients in Masimo group and 3084 patients in HemoCue group). In
      the Masimo group, the overall mean difference was -0.03 g/dl (95% prediction
      interval -0.30 to 0.23) and 95% limits of agreement -3.0 to 2.9 g/dl compared to
      0.08 g/dl (95% prediction interval -0.04 to 0.20) and 95% limits of agreement 
      1.3 to 1.4 g/dl in the HemoCue group. Only B-Hemoglobin exhibited bias (0.53, 95%
      prediction interval 0.27 to 0.78). The overall standard deviation of difference
      was larger (1.42 g/dl versus 0.64 g/dl) for Masimo pulse co-oximeters compared to
      HemoCue photometers. Masimo devices and HemoCue 201+ both provide an unbiased,
      pooled estimate of laboratory haemoglobin. However, Masimo devices have lower
      precision and wider 95% limits of agreement than HemoCue devices. Clinicians
      should carefully consider these limits of agreement before basing transfusion or
      other clinical decisions on these point-of-care measurements alone. 

PMID- 25943610
TI  - The relationship between superior vena cava diameter and collapsibility and
      central venous pressure.
AB  - The aim of this study was to assess the relationship between superior vena cava
      (SVC) diameter, collapsibility and central venous pressure (CVP) in cardiac
      surgical patients. SVC maximum and minimum diameters, plus collapsibility with
      ventilation, were measured with transoesophageal echocardiography in the mid
      oesophageal bicaval view with M-mode. Simultaneously, CVP was measured via the
      right atrial port of a pulmonary artery catheter. Measurements were possible in
      91 out of 92 patients. The median CVP was 10 mmHg with a range of 2 to 19 mmHg.
      There was a weak, but statistically significant, correlation between CVP and SVC
      collapsibility index (r=-0.21, P=0.049). There was no statistically significant
      correlation between maximum SVC diameter and CVP. Maximum SVC diameter was
      statistically significantly correlated with weight (Pearson's r=0.28, P=0.008).
      There was no statistically significant correlation between CVP and age or body
      dimensions. Our findings indicate that SVC diameter and collapsibility are easily
      measured with transoesophageal echocardiography but do not reliably reflect CVP
      in anaesthetised cardiac surgical patients. 

PMID- 25943609
TI  - Selective unilateral spinal anaesthesia for outpatient knee arthroscopy using
      real-time monitoring of lower limb sympathetic tone.
AB  - Selective unilateral spinal anaesthesia is a useful approach for ambulatory lower
      limb surgery because it allows more rapid home discharge compared to bilateral
      block. Infrequent use is due to the fact that obtaining selective unilateral
      block can be difficult, requiring attention to technique. We present a method
      with a high success rate that uses real-time monitoring of the sympathetic
      activity of the legs. In this prospective study, 56 patients scheduled for
      ambulatory knee arthroscopy had spinal anaesthesia in the lateral recumbent
      position, with hyperbaric bupivacaine 0.5% injected at 0.33 ml/min up to a
      maximum dose of 5 mg. Sympathetic tone of the legs was monitored by plantar
      electrical dermal resistance. The clinical effect was assessed by loss of
      sensation and muscle strength. The haemodynamic course and adverse events were
      monitored. The motor block was strictly unilateral in 55 patients (98%) and the
      sensory block was strictly unilateral in 53 patients (94%). The median decrease
      in systolic blood pressure was 6 mmHg. The time from subarachnoid puncture to
      arrival in the recovery room was 73+/-23 minutes; the duration of stay in the
      recovery room was 70+/-30 minutes. Three patients with a well-established block
      of adequate extent required conversion to general anaesthesia because of
      tourniquet pain. Urinary retention only occurred in the sole patient with
      bilateral block. This method of performing selective unilateral spinal
      anaesthesia using real-time monitoring of sympathetic tone of the legs has a high
      success rate and is associated with rapid eligibility for home discharge.

PMID- 25943611
TI  - Predicting intensive care and hospital outcome with the Dalhousie Clinical
      Frailty Scale: a pilot assessment.
AB  - Frailty may help to predict intensive care unit (ICU) patient outcome. The
      Dalhousie Clinical Frailty Scale (DCFS) is validated to assess frailty in
      ambulatory settings but has not been investigated in Australian ICUs. We
      conducted a prospective three-month study of patients admitted to a tertiary
      level ICU. Within 24 hours of ICU admission, the next of kin or nurse in charge
      assigned a DCFS score to the patient. Data were obtained to assess the
      association between frailty and patient outcome. The DCFS score was completed in
      205 of 348 (59%) of eligible patient admissions. The mean DCFS score was 3.2 (+/
      1.6). Overall frailty (DCFS>4) occurred in 28 of 205 patients (13%, confidence
      interval 9% to 17%), 13 of 93 (15%, confidence interval 10% to 25%) in patients
      aged >65 years and 5 of 11 (45%, confidence interval 21% to 71%) in those>85
      years. Patients with chronic liver disease (P<0.001) and end-stage renal failure
      (P=0.009) were more likely to be frail. The DCFS score was not significantly
      associated with ICU or hospital mortality: odds ratio 0.98 (95% confidence
      interval 0.6 to 1.6) and odds ratio 1.07 (95% confidence interval 0.8 to 1.4),
      respectively. However, after adjustment for illness severity and requirement for
      palliative care, the DCFS score was significantly associated with increased (log)
      hospital length-of-stay (P=0.04) and age (P=0.001). Approximately 1 in 10 ICU
      patients were frail and this frequency increased with age. The DCFS was
      associated with patient age and comorbidities and potentially predicts increased
      hospital length-of-stay but not other outcomes. Strategies to improve compliance
      with DCFS completion are needed.

PMID- 25943612
TI  - Findings of the first ANZICS conference on the role of intensive care in Rapid
      Response Teams.
AB  - Rapid Response Teams (RRTs) are specialised teams introduced into hospitals to
      improve the outcomes of deteriorating ward patients. Although Rapid Response
      Systems (RRSs) were developed by the intensive care unit (ICU) community, there
      is variability in their delivery, and consultant involvement, supervision and
      leadership appears to be relatively infrequent. In July 2014, the Australian and
      New Zealand Intensive Care Society (ANZICS) convened the first conference on the
      role of intensive care medicine in RRTs in Australia and New Zealand. The
      conference explored RRSs in the broader role of patient safety, resourcing and
      staffing of RRTs, effect on ICU workload, different RRT models, the outcomes of
      RRT patients and original research projects in the area of RRSs. Issues around
      education and training of both ICU registrars and nurses were examined, and the
      role of team training explored. Measures to assess the effectiveness of the RRS
      and RRT at the level of health system and hospital, team performance and team
      effectiveness were discussed, and the need to develop a bi-national ANZICS RRT
      patient database was presented. Strategies to prevent patient deterioration in
      the 'pre-RRT' period were discussed, including education of ward nurses and
      doctors, as well as an overarching governance structure. The role of the ICU in
      deteriorating ward patients was debated and an integrated model of acute care
      presented. This article summarises the findings of the conference and presents
      recommendations on the role of intensive care medicine in RRTs in Australia and
      New Zealand.

PMID- 25943613
TI  - Inclusion of financial issues in the surgery cancellation categories introduced
      by Emanuel et al.

PMID- 25943614
TI  - In response to Katsiampoura et al.

PMID- 25943615
TI  - Intentional oesophageal intubation for managing regurgitation during endotracheal
      intubation.

PMID- 25943616
TI  - Impact of anaesthesia on outcomes after radiocephalic arteriovenous fistula
      creation.

PMID- 25943617
TI  - A pictorial display of contents for quick revision: improving the efficacy and
      efficiency of cricothyroidotomy kits.

PMID- 25943618
TI  - Lactic acidosis and asymptomatic hypoglycaemia due to plasmablastic lymphoma.

PMID- 25943619
TI  - Successful conservative management of an iatrogenic ECMO cannula--related
      inferior vena cava injury.

PMID- 25943620
TI  - Morbidity and mortality in patients admitted with submandibular space infections
      to the intensive care unit.

PMID- 25943621
TI  - Outcomes and clinical characteristics of critically ill patients requiring
      inferior vena cava filters in a tertiary referral centre.

PMID- 25943622
TI  - A dilemma while achieving rapid reversal of anticoagulation in a rural setting.

PMID- 25943623
TI  - Self-directed simulator echocardiography training: a scalable solution.

PMID- 25943624
TI  - Unusual volatile agent switch: implications for checking unsealed volatile agent
      containers.

PMID- 25943625
TI  - Feasibility and safety of catheter ablation of electrical storm in ischemic
      dilated cardiomyopathy.
AB  - AIMS: Electrical storm is an emergency in 'implantation of a cardioverter
      defibrillator' carriers with ischemic dilated cardiomyopathy (DCM) and negatively
      impacts long-term prognosis. We evaluated the feasibility, safety, and
      effectiveness of radiofrequency catheter ablation (RFCA) in controlling
      electrical storm and its impact on survival and ventricular
      tachycardia/fibrillation recurrence. METHODS: We enrolled 27 consecutive patients
      (25 men, age 73.1 +/- 6.5 years) with ischemic DCM and an indication to RFCA for
      drug-refractory electrical storm. The immediate outcome was defined as failure or
      success, depending on whether the patient's clinical ventricular tachycardia
      could still be induced after RFCA; electrical storm resolution was defined as no
      sustained ventricular tachycardia/ventricular fibrillation in the next 7 days.
      RESULTS: Of the 27 patients, 1 died before RFCA; in the remaining 26 patients, a
      total of 33 RFCAs were performed. In all 26 patients, RFCA was successful,
      although in 6/26 patients (23.1%), repeated procedures were needed, including
      epicardial ablation in 3/26 (11.5%). In 23/26 patients (88.5%), electrical storm
      resolution was achieved. At a follow-up of 16.7 +/- 8.1 months, 5/26 patients
      (19.2%) had died (3 nonsudden cardiac deaths, 2 noncardiac deaths) and 10/26
      patients (38.5%) had ventricular tachycardia recurrence; none had electrical
      storm recurrence. A worse long-term outcome was associated with lower glomerular
      filtration rate, wider baseline QRS, and presence of atrial fibrillation before
      electrical storm onset. CONCLUSION: In patients with ischemic DCM, RFCA is well
      tolerated, feasible and effective in the acute management of drug-refractory
      electrical storm. It is associated with a high rate of absence of sustained
      ventricular tachycardia episodes over the subsequent 7 days. After successful
      ablation, long-term outcome was mainly predicted by baseline clinical variables.

PMID- 25943626
TI  - Epidemiology and outcomes of peripartum cardiomyopathy in the United States:
      findings from the Nationwide Inpatient Sample.
AB  - AIMS: Peripartum cardiomyopathy (PPCM) is defined as systolic heart failure
      within the last month of pregnancy or 5 months after delivery in the absence of
      any identifiable cause of heart failure. We aimed to investigate the prevalence
      of PPCM and predictors of in-hospital mortality in patients with PPCM. METHODS:
      We analyzed patients with diagnosis of PPCM from the Nationwide Inpatient Sample
      database using the Ninth Revision of International Classification of Diseases
      (ICD-9) from 2009 to 2010. We categorized PPCM (n = 4871) into three groups of
      presentation based on their ICD-9 codes: antepartum (674.53; n = 189), peripartum
      (674.51, 674.52; n = 887) and postpartum (674.54; n = 3741). RESULTS: PPCM was
      more common in African-Americans (43.9%) as compared with white (40.8%), Hispanic
      (8.7%) and Asian (2.7%) women. Hypertensive disorders were classified as pre
      existing hypertension (31.6%), gestational hypertension (3.7%), preeclampsia
      (9.9%), eclampsia (2.4%) and preeclampsia/eclampsia superimposed on hypertension
      (3.1%). Among different ethnicities, pre-existing hypertension (1 : 2.3) and
      diabetes (1 : 10.4) were more prevalent in African-Americans, whereas
      preeclampsia (1 : 4.3) and premature labor (1 : 5.4) were more common in Asians.
      In-hospital mortality rate was 1.8%, with 2.1% in the postpartum and 0.5% in the
      peripartum group. Asians had the highest mortality (8.3%). In multimodel
      regression analysis, Asians [odds ratio (OR) 9.68, 95% confidence interval (CI)
      1.11-83.9, P = 0.03] and length of stay (OR 1.06, 95% CI 1.03-1.10, P < 0.01)
      were associated with increased mortality, whereas white women were associated
      with reduced mortality (OR 0.10, 95% CI 0.02-0.59, P = 0.01). CONCLUSION:
      Although PPCM was prevalent in African-Americans, Asians had higher in-hospital
      mortality, increased prevalence of preeclampsia and premature labor. Also,
      mortality rate was significantly higher in the postpartum group.

PMID- 25943627
TI  - Symptomatic males and female carriers in a large Caucasian kindred with XIAP
      deficiency.
AB  - PURPOSE: X-linked inhibitor of apoptosis (XIAP) deficiency caused by mutations in
      BIRC4 was originally described in male patients with X-linked lymphoproliferative
      syndrome type 2 (XLP2). Recent observations have highlighted a critical role of
      XIAP for the regulation of NOD2 signaling and are probably the molecular basis
      for increasingly recognized further immune dysregulatory symptoms of XIAP
      deficient patients, such as inflammatory bowel disease (IBD). We describe a large
      Caucasian family in which IBD and erythema nodosum (EN) also manifested in female
      carriers of XIAP mutations. METHODS: Clinical data and laboratory findings
      including flow cytometric analysis of XIAP protein expression and sequencing of
      the BIRC4 gene. NOD2 signaling was investigated by determination of TNFalpha
      production in monocytes upon L18-MDP stimulation in vitro. RESULTS: The BIRC4
      nonsense mutation p.P225SfsX226 was identified as the genetic cause of XIAP
      deficiency in our family. Surprisingly, clinical symptoms were not restricted to
      male patients, but also occurred in several female carriers. The most severely
      affected carrier demonstrated random X-inactivation, leading to a significant
      expression of mutated XIAP protein in monocytes, and consequently to impaired
      NOD2 responses in vitro. CONCLUSION: Our report provides further evidence that
      clinical symptoms of XIAP deficiency are not restricted to male patients. Random
      X-inactivation may be associated with EN and mild IBD also in female carriers of
      BIRC4 mutations. Analysis of the X-inactivation pattern reflected by XIAP protein
      expression can identify such carriers and the analysis of NOD2 signaling by flow
      cytometry can confirm the functional significance. XIAP expression patterns
      should be investigated in female patients with a family history of EN and/or IBD.

PMID- 25943628
TI  - In vitro expression of Streptococcus pneumoniae ply gene in human monocytes and
      pneumocytes.
AB  - BACKGROUND: Streptococcus pneumoniae is one major cause of pneumonia in human and
      contains various virulence factors that contribute to pathogenesis of
      pneumococcal disease. This study investigated the role of pneumolysin, Ply, in
      facilitating S. pneumoniae invasion into the host blood stream. METHODS: S.
      pneumoniae strains were isolated from clinical blood and sputum samples and
      confirmed by PCR. Expression of ply gene was assessed by infecting human
      monocytes and pneumocytes. RESULTS: A total of 23 strains of S. pneumoniae
      isolated from blood (n = 11) and sputum (n = 12) along with S. pneumoniae
      ATCC49619 were used to infect human monocyte (THP-1) and Type II pneumocyte
      (A549) cell lines. All clinical strains of S. pneumoniae showed higher expression
      of ply mRNA than the American Type Culture Collection (ATCC) strain. Among the
      clinical strains, blood isolates showed higher expression of ply genes than
      sputum isolates, i.e., 2(1.5)- to 2(1.6)-folds in THP-1 and 2(0.4)- to 2(4.9)
      folds in A549 cell lines. CONCLUSIONS: The data from the current study
      demonstrated that ply gene of blood- and sputum-derived S. pneumoniae is
      differentially expressed in two different cell lines. Under survival pressure,
      ply is highly expressed in these two cell lines for blood-derived S. pneumoniae,
      indicating that ply gene may facilitate S. pneumoniae invasion into the host
      blood system.

PMID- 25943629
TI  - Is the state of health of rheumatoid arthritis patients receiving adequate
      treatment, predictable? - Results of a survey.
AB  - BACKGROUND: A survey was conducted to evaluate whether a steady improvement in
      the quality of life of Rheumatoid Arthritis (RA) patients as frequently reported
      in clinical studies, does actually occur. The focus of this study laid on the
      personal perception of RA patients. How do patients who have been treated along
      accepted guidelines see the state of their health and their joint pain at
      different points in time? METHODS: RA patients were asked to complete a
      questionnaire and return it to an opinion research centre. The questionnaire,
      which was developed by the authors, was divided into the areas: demography,
      symptom description and medical care, as well as the illness in a personal
      context. Three telephone interviews followed in monthly intervals when the
      patients' feelings about their illness, their every-day coping mechanisms and
      their social lives were rated. Intra-subject correlation and the level of
      agreement among patients when assessed at three different points within a two
      month period, was determined. RESULTS: 127 patients replied to the questionnaire.
      RA exerts a significant impact on a patient's daily life. Average ratings of
      current state of health and joint pain (answered on a 5-part scale extending from
      1 (very good) to 5 (very bad)) range between 2.6 and 2.9 all three times.
      However, intra-subject correlation between the different assessment times, is in
      general quite modest. Concerning the question: "How is your join pain today?"
      only 14 of 127 participants express identical ratings all three times , while in
      one third of the participants, a difference of two digits on the 5-part scale, at
      least twice had to be noticed. Intra-class correlation coefficients between
      answers at different points are often much smaller than 0.5. Results were similar
      in all subgroups analysed (men vs. women; patients receiving biologics vs. those
      not receiving biologics; disease duration <=3 years vs. 4 to 10 years vs. >=11
      years). CONCLUSION: On an individual level personal assessments of health, well
      being and joint pain are nevertheless unsteady even within the timeframe of two
      months. This is why, even now, RA patients still cannot plan their lives as non
      affected people can.

PMID- 25943630
TI  - Bilateral pulmonary emboli associated with intraoperative use of thrombin-based
      hemostatic matrix following lumbar spine interbody fusion.
AB  - Here we describe a patient with bilateral pulmonary emboli (PE) associated with
      thrombin-based hemostatic matrix (TBHM) use in the setting of a possible venous
      injury during transforaminal lumbar interbody fusion in the treatment of
      degenerative spondylolisthesis at L4-5. TBHM products are gelatin granules mixed
      with human or bovine thrombin. They have been used in a wide variety of surgical
      procedures to facilitate local hemostasis though their use is not without
      complications. This is the first reported patient, to our knowledge, with a TBHM
      related PE following spinal fusion. As TBHM is a widely used intraoperative
      hemostatic agent, surgeons should be aware of the risk of TBHM-associated PE,
      particularly when there is the potential for intravascular injection or
      dissemination. While our experience indicates that common pharmacological
      prophylaxis such as subcutaneous heparin is likely ineffective in reducing
      occurrence of PE in the setting of TBHM use, the PE was successfully treated with
      standard systemic anticoagulation. The authors would also add that when iliac
      injury is encountered during discectomy or interbody fusion through a posterior
      approach, use of TBHM may be a life-saving technique. Postoperatively, vascular
      surgery consultation is recommended and consideration should be given to systemic
      anticoagulation. 

PMID- 25943631
TI  - Sudden unexpected death in epilepsy following resective epilepsy surgery in two
      patients withdrawn from anticonvulsants.
AB  - We report sudden unexpected death in epilepsy (SUDEP) following resective
      epilepsy surgery in two patients who had been documented as seizure free. One
      patient had been weaned off of anticonvulsants and was leading a normal life. The
      other patient had discontinued only one anticonvulsant but had recently started
      working night shifts. Following resective epilepsy surgery, one of the major
      objectives among patients, caregivers, and the healthcare team is to safely wean
      patients off anticonvulsant medications. The main concern regarding
      anticonvulsant withdrawal is seizure recurrence. While SUDEP following surgical
      resection has been reported, to our knowledge, there have been no confirmed cases
      in patients who have been seizure free. Considering the patients reported here,
      and given that there are no concrete guidelines for the safe withdrawal of
      anticonvulsants following epilepsy surgery, the discontinuation of
      anticonvulsants should be considered carefully and must be accompanied by close
      monitoring and counseling of patients regarding activities that lower seizure
      threshold, even after successful epilepsy surgery. 

PMID- 25943633
TI  - MiR-27a modulates radiosensitivity of triple-negative breast cancer (TNBC) cells
      by targeting CDC27.
AB  - BACKGROUND: MiR-27a is significantly overexpressed in triple-negative breast
      cancer (TNBC). However, the exact biological function of MiR-27a in TNBC is not
      fully understood. In this study, we verified miR-27a expression in TNBC cells and
      explored how its overexpression modulates radiosensitivity of the cells.
      MATERIAL/METHODS: qRT-PCR analysis was performed to study miR-27a expression in
      TNBC lines MDA-MB-435 and MDA-MB-231 and in normal human breast epithelial cell
      line MCF10A. Dual luciferase assay was performed to verify a putative downstream
      target of miR-27a, CDC27. CCK-8 assay was used to assess the influence of miR-27a
      CDC27 axis on cell proliferation under irradiation (IR) treatment. RESULTS: We
      confirmed significantly higher miR-27a expression in 2 TNBC cell lines--MDA-MB
      435 and MDA-MB-231--than in human breast epithelial cell line MCF10A. miR-27a
      could modulate proliferation and radiosensitivity of TNBC cells. CDC-27 is a
      direct target of miR-27a and its downregulation conferred increased
      radioresistance of the cells. CONCLUSIONS: The miR-27a-CDC27 axis might play an
      important role in modulating response to radiotherapy in TNBC cells. Testing miR
      27a expression might be a useful way to identify a subgroup of patients who will
      benefit from an IR-based therapeutic approach.

PMID- 25943632
TI  - A possible new focus for stroke treatment - migrating stem cells.
AB  - INTRODUCTION: Stroke is a leading cause of mortality in the US. More so, its
      infliction often leaves patients with lasting morbidity and deficits. Ischemic
      stroke comprises nearly 90% of incidents and the majority of medical treatment
      aims at reestablishing perfusion and preventing recurrence. AREAS COVERED: Long
      term options for neurorestoration are limited by the infancy of their innovative
      approach. Accumulating evidence suggests the therapeutic potential of stem cells
      in neurorestoration, however, proper stem cell migration remains a challenge in
      translating stem cell therapy from the laboratory to the clinic. In this paper,
      we propose the role that exogenous stem cell transplantation may serve in
      facilitating the migration of endogenous stem cells to the site of injury, an
      idea termed 'biobridge'. EXPERT OPINION: Recent research in the field of
      traumatic brain injury has provided a foundational understanding that, through
      the use of exogenous stem cells, native tissue architecture may be manipulated by
      proteinases to allow better communication between the endogenous sites of neural
      stem cells and the regions of injury. There is still much to be learned about
      these mechanisms, though it is the devastating nature of stroke that necessitates
      continued research into the prospective therapeutic potential of this novel
      approach.

PMID- 25943634
TI  - miR-24-2 regulates genes in survival pathway and demonstrates potential in
      reducing cellular viability in combination with docetaxel.
AB  - MicroRNAs the small (18-22 in length) noncoding RNA molecules are negative
      regulators of gene expression, modulating biological processes of cell
      differentiation, survival and death. The latter two phenomena are critical in
      tumour biology. We provide here the results of human genome wide target
      prediction of one such microRNA, hsa-miR-24-2, shown to target genes essential
      for initiating cellular stability and cell survival. The protein-protein
      interaction study showed important nodes which could affect cell cycle
      progression and differential oncogenesis. An analysis of hsa-miR-24-2 in sporadic
      breast tumours showed a negative correlation with metastasis and increasing
      nodes. The conclusion drawn of hsa-miR-24-2 targeting the genes of cell survival
      correlated with the methylation profile and resultant transcription factor
      binding site gain or loss in support of absence of cell survival. In order to
      accentuate the potential of hsa-miR-24-2 to reduce cellular viability under
      experimental conditions, in vitro studies in the presence and absence of anti
      cancer drugs, such as docetaxel resulted in a significant decrease in cellular
      viability even at a 200-fold reduced dose of the drug in combination with hsa-miR
      24-2. 

PMID- 25943635
TI  - A functionally critical single nucleotide polymorphism in the gene encoding the
      membrane-bound alcohol dehydrogenase found in ethanol oxidation-deficient
      Gluconobacter thailandicus.
AB  - The Gluconobacter thailandicus strains NBRC3254, NBRC3255, NBRC3256, NBRC3257,
      and NBRC3258 are naturally deficient in the ethanol-oxidizing respiratory chain
      because they do not produce the cytochrome subunit of the membrane-bound alcohol
      dehydrogenase (ADH). Draft genomes of G. thailandicus strains NBRC3255 and
      NBRC3257 indicated that the adhB gene encoding the cytochrome subunit contains
      four base differences when compared to a closely related gene in the public
      database One of the nucleotide differences results in an Opal codon at the -19th
      tryptophan (Trp) in the signal sequence for translocation to the periplasmic
      space (here, the position of +1st residue is assigned to the N-terminal amino
      acid residue after signal peptide cleavage), while the other differences result
      in one missense and two silent amino acid alterations. All five of the G.
      thailandicus strains were shown to have the Trp(-19)Opal alteration. Ethanol
      oxidation and ADH activities in NBRC3255 were restored by transformation with a
      derivative of the endogenous adhB gene, of which the -19th Opal codon was altered
      to encode Trp. These results indicate that this sequence is a functionally
      critical single nucleotide polymorphism in the cytochrome subunit. Comparative
      genomic analyses between the draft genomes of NBRC3255 and NBRC3257 revealed that
      although the two genomes are closely related, they both have a significant number
      of unique open reading frames. We suggest that the closely related NBRC3255 and
      NBRC3257 diverged from a common ancestor having the mutation in the adhB gene,
      whereas no additional functionally critical mutation occurred in the adhB
      pseudogene over the course of evolution. 

PMID- 25943636
TI  - Iron deficiency stress can induce MxNRAMP1 protein endocytosis in M.
      xiaojinensis.
AB  - BACKGROUND: Iron deficiency is one of the most common nutritional disorders in
      plants, especially in fruit trees grown in calcareous soil. Iron deficiency
      stress can induce a series of adaptive responses in plants, the cellular and
      molecular mechanisms of which remain unclear. NRAMPs (natural resistance
      associated macrophage proteins) play an important role in divalent metal ion
      transportation. RESULTS: In this study, we cloned MxNRAMP1, an NRAMP family gene
      from a highly iron-efficient apple genotype, Malus xiaojinensis. Further research
      showed that iron deficiency stress could induce MxNRAMP1 expression in roots and
      leaves. A protoplast transient expression system and immune electron microscopy
      localization techniques were used to prove that MxNRAMP1 mainly exists in the
      plasma membrane and vesicles. Interestingly, iron deficiency stress could induce
      the MxNRAMP protein to transport iron ions to specific organelles (lysosome and
      chloroplast) through vesicle endocytosis. Stable transgenic tobacco showed that
      MxNRAMP1 over-expression could promote iron absorption and accumulation in
      plants, and increase the plant's resistance against iron deficiency stress.
      CONCLUSIONS: These results showed that, in M. xiaojinensis, MxNRAMP1 not only
      plays an important role in iron absorption and transportation, it can also
      produce adaptive responses against iron deficiency through endocytosis.

PMID- 25943637
TI  - The relative expression levels of insulin-like growth factor 1 and myostatin mRNA
      in the asynchronous development of skeletal muscle in ducks during early
      development.
AB  - Genetic selection is a powerful tool for modifying poultry muscle yield. Insulin
      like growth factor I (IGF-I) and myostatin (MSTN) are important regulators of
      muscle growth, especially in the myogenesis stage. This study compared the
      developmental pattern of the pectoralis major (PM) and lateral gastrocnemius (LM)
      muscles, mRNA expression characterization of IGF-I and MSTN-A and their
      correlation between 14 days in ovo and 1 week post-hatch in two Chinese local
      duck breeds. During early development, the growth of duck PM and LM followed an
      asynchronous pattern. Variations in PM growth rate observed with development
      followed the relative variations of MSTN and IGF-I expression; however, the same
      behavior was not observed in LM. Moreover, the profile of IGF-I expression in
      duck skeletal muscles indicated that genetic selection for high meat-yield
      poultry has altered the temporal expression of IGF-I and affected cellular
      characteristics and mass by hatch in a PM-specific manner. The MSTN-A expression
      profile showed synchronization with the growth of skeletal muscle and peaks of
      myofiber proliferation. The expression patterns of IGF-I and MSTN suggest that
      duck pectoralis fibers are prioritized for proliferation in embryogenesis. The
      IGF-1/MSTN-A mRNA ratios in PM and LM presented very similar trends in the
      changes of myofiber characteristics, and differences in the IGF-1/MSTN-A mRNA
      ratio in PM between the two breeds corresponded to the timing of differences in
      PM mass between the varieties. Our results support the hypothesis that relative
      levels of IGF-I and MSTN mRNA may participate in ordering muscle growth rates
      with selected development.

PMID- 25943638
TI  - Pregnancy and pulmonary arterial hypertension: A clinical conundrum.
AB  - Pulmonary arterial hypertension (PAH) is a rare and devastating disease
      characterized by progressive increases in pulmonary arterial pressure and
      pulmonary vascular resistance which eventually leads to right ventricular failure
      and death. PAH inflicts most commonly women, majority of who are of childbearing
      age. Pregnancy in the setting of PAH is absolutely contraindicated due to high
      maternal fetal morbidity and guidelines do not exist for the management of such
      cases. A MEDLINE/PubMed search was performed identifying all relevant articles
      with "pulmonary arterial hypertension" and "pregnancy" in the title. Six case
      series were reviewed as well as our own center's experience outlined. Though
      there exists generalized treatment measures that are followed in such cases,
      management varies among different national centers as well an on an international
      level. At our center patients are managed using a multidisciplinary approach at a
      high risk obstetric center with preference for intravenous prostacyclin therapy.
      Women of child bearing age with possible signs and symptoms of PAH must be
      promptly diagnosed and managed expectantly with an emphasis on maternal-fetal
      safety. 

PMID- 25943639
TI  - Pregnancy outcomes in women with heart disease: Experience of a tertiary center
      in the Netherlands.
AB  - OBJECTIVES: Clinical data of pregnant women with heart disease were obtained with
      the intention to provide input for local counseling and management guidelines.
      STUDY DESIGN: Retrospective data from all pregnant women with congenital or
      acquired heart disease between 2000 and 2011 in the VU University Medical Centre
      Amsterdam. MAIN OUTCOME MEASURES: Maternal and neonatal outcomes were evaluated.
      RESULTS: Data of 122 women with 160 pregnancies were obtained. The most common
      heart diseases were congenital heart disease (n=65, 53.3%) and arrhythmia (n =
      20, 16.4%). Based on the functional criteria of the New York Heart Association
      (NYHA), 114/122 patients (93.4%) were classified NYHA class I-II. Patients in
      NYHA class III-IV (n = 8/122, 6.6%), mainly had a history of myocardial
      infarction or pulmonary hypertension. There were 156 singleton and 4 twin
      pregnancies. 22 (13.5%) pregnancies were complicated by hypertensive disorders.
      Heart failure developed in 11 women (9.0%), 37.5% in NYHA class III-IV and 6.5%
      in NYHA class I-II. Mean gestational age and birth weight were 270 days and 3196
      g in NYHA class I-II compared to 237 days and 1972 g for NHYA class III-IV. There
      were two maternal deaths (1.6%) and 5 fetal deaths (3.1%). There were 29 (12.8%)
      preterm births, 20 (12.8%) neonates small for gestational age and 34 (21.8%)
      admittances on the Neonatal Intensive Care Unit (NICU). CONCLUSIONS: Pregnancy in
      women with pre-existing heart disease in all NYHA classes is associated with
      increased maternal morbidity and perinatal morbidity. Risk of structural fetal
      anomalies is especially high in women with congenital heart disease.

PMID- 25943640
TI  - Is gestational hypertension beneficial in twin pregnancies?
AB  - OBJECTIVES: Hypertensive disorders of pregnancy are commonly associated with
      impaired foetal growth. However, some studies observed that gestational
      hypertension in twin pregnancy could be beneficial for foetal growth. The aim of
      this study is to investigate the influence of gestational hypertension on
      neonatal birth weight among twin pregnancies. STUDY DESIGN: This is a
      retrospective study about the comparison of 196 hypertensive twin pregnancies to
      912 normotensive ones, who gave birth in the teaching hospital "A. Gemelli" in
      Rome from 1980 to 2006. MAIN OUTCOME MEASURES: Birth weight, inter-twin weight
      discordance and rate of small for gestational age neonates in the first and
      second twin. RESULTS: Birth weight, inter-twin weight discordance and rate of
      small for gestational age neonates were similar between the two groups. In the
      normotensive group, the discordance >25% was associated with lower gestational
      age at the delivery (p<0.00001), data not observed in the hypertensive group. The
      rate of pregnancies with second twin small for gestational age rose while
      paralleling the degree of the discordance in both groups. CONCLUSION: Gestational
      hypertension in twin pregnancies, if compared to normotensive ones, is not
      detrimental for foetal growth.

PMID- 25943641
TI  - Haemodynamic assessment in pregnancy and pre-eclampsia: A Guytonian approach.
AB  - OBJECTIVES: Hypertensive disorders of pregnancy continue to be amongst the
      leading causes of maternal morbidity and mortality. There is debate about the
      optimal monitoring and treatment for these women, particularly in regard to
      circulatory and fluid management. A restrictive fluid strategy is advocated,
      which conflicts with the prevailing view that the circulating volume is
      contracted in pre-eclampsia. This belief has been erroneously reinforced by use
      of the central venous pressure (CVP) as a measure of the volume state. METHODS:
      We used a Guytonian model of the circulation involving the mean systemic filling
      pressure (Pms) to review published data using a cohort of normal pregnant/post
      partum women and a pre-eclamptic cohort. The Pms is the pressure left in the
      circulation when the heart is stopped, arguably the true volume state measure. An
      analogue of the Pms (Pmsa) can be calculated using commonly measured haemodynamic
      variables. RESULTS: Our results show the Pmsa to be elevated in normal pregnancy
      versus post partum (10.79 vs. 9.58, a 12.6% difference) and elevated further in
      pre-eclamptic pregnancy (13.86, 29% higher than the normal pregnant group).
      CONCLUSIONS: There is scope to challenge the long held belief that the volume
      state is contracted in pre-eclampsia. This approach indicates that the maternal
      volume state in pre-eclampsia is often elevated. When viewed in combination with
      recent echocardiographic insights this model helps to explain some of the
      haemodynamic management paradoxes that these women present. Most importantly, it
      provides a sound physiological basis for the restrictive fluid strategy that is
      currently recommended.

PMID- 25943643
TI  - Left ventricular remodeling and diastolic function in chronic hypertensive
      pregnant women.
AB  - Hypertension during pregnancy is a problem that impacts maternal morbidity and
      mortality. Dyspnea and edema are common symptoms, often secondary to
      physiological changes, but may raise doubts as to ventricular dysfunction.
      OBJECTIVE: To evaluate the ventricular geometry pattern and diastolic function in
      chronic hypertensive pregnant women (HPW). METHODS: Prospective, cross-sectional
      study on 62 pregnant women over a 29-month period, from March 2009 to July 2011,
      in Brazil was done. Thirty-one HPWs and 31 normotensive pregnant women (NPW)
      underwent clinical and cardiovascular evaluations, and were subjected to
      transthoracic echocardiogram. RESULTS: LV mass (HPW: 220.9 +/- 43.3 vs. NPW:
      192.9 +/- 39.8 g, p = 0.01), posterior wall thickness (HPW: 9.9 +/- 1.1 vs. NPW:
      9.2 +/- 0.9 mm, p = 0.005), mitral flow A wave velocity (HPW: 0.60 +/- 0.16 vs.
      NPW: 0.52 +/- 0.10 m/s, p = 0.02), tissue Doppler A' wave velocity (HPW: 10 +/- 2
      vs. NPW: 8.9 +/- 1cm/s, p=0.02), and E/E' ratio (HPW: 6.8 +/- 2.2 vs. NPW: 5.5 +/
      1.6, p = 0.01) were higher in HPWs. Septal and lateral walls E' wave velocities
      (HPW: 13 +/- 2 vs. NPW: 15 +/- 3 cm/s, p=0.001), and E'/A' ratio (HPW: 1.26 +/-
      0.38 vs. NPW: 1.77 +/- 0.49, p = 0.00003) were lower in HPWs. There was a
      positive linear correlation between body mass index (BMI) and ventricular mass, A
      wave, systolic, diastolic blood pressures, and a negative correlation between
      BMI, E' wave and E'/A' ratio. CONCLUSION: Ventricular remodeling showed a direct
      relationship with body weight, and both groups showed a predominant pattern of
      eccentric ventricular hypertrophy. The LV diastolic function was abnormal in
      HPWs.

PMID- 25943642
TI  - Evaluation of specificity and sensitivity of gastric aspirate shake test to
      predict surfactant deficiency in Iranian premature infants.
AB  - INTRODUCTION: Respiratory failure secondary to pulmonary surfactant deficiency is
      an important cause of severe respiratory distress in term and preterm infants.
      The aim of this study was to evaluate the specificity and sensitivity of gastric
      aspirate shake test (GAST) to predict surfactant deficiency in newly born
      premature infants in Arash Hospital (Iran) during 2012-13. METHODS: In this case
      control study, the case group comprised 69 premature infants (gestational age<37
      weeks) who were admitted to the neonatal intensive care unit due to respiratory
      distress. The control group included 50 healthy infants .GAST test was done. The
      subjects were finally categorized as healthy or surfactant-deficient based on
      clinical and radiological assessments. RESULTS: Using statistical methods the
      sensitivity, specificity, and positive and negative predictive values of GAST
      were 60%, 75%, 15%, and 52%, respectively. There was a significant difference
      between respiratory distress syndrome (RDS) scores and receiving surfactant in
      neonates with gestational age below 34 weeks. Moreover, there were significant
      differences between GAST results and both radiological findings of RDS and
      receiving oxygen in premature infants (gestational age<34 weeks). Negative GAST
      results were more prevalent in neonates who were born to mothers with
      hypothyroidism, preeclampsia, diabetes mellitus, and premature rupture of
      membranes. However, this difference was not significant. CONCLUSION: According to
      our findings, the application of GAST on gastric aspirate secretions is not a
      useful method to predict surfactant deficiency. Therefore, decisions for RDS
      management must be made based on clinical and radiological findings.

PMID- 25943644
TI  - Assessment of total vascular resistance and total body water in normotensive
      women during the first trimester of pregnancy. A key for the prevention of
      preeclampsia.
AB  - INTRODUCTION: Maternal cardiovascular system adapts to pregnancy, thanks to
      complex physiological mechanisms that involve cardiac output, total vascular
      resistance and water body distribution. Abnormalities of these adaptive
      mechanisms are connected with hypertensive disorders. OBJECTIVE: To identify
      patients at a high risk of developing hypertensive complications of pregnancy
      during the first trimester of pregnancy, through the use of non-invasive methods
      such as USCOM (Ultrasonic Cardiac Output Monitor) and Bioimpedance. MATERIALS AND
      METHODS: We enrolled 120 healthy normotensive women during the first trimester of
      pregnancy obtaining all measurements with the USCOM system and Bioimpedance.
      RESULTS: 20 patients were excluded for a bad USCOM signal. The remaining patients
      (n = 100) were retrospectively divided into two groups: Group A (n = 75) TVR<1200
      dynes s cm(-5), Group B (n = 25) TVR>1200 dynes s cm(-5). No statistically
      significant difference was identified in terms of water distribution, Fat Free
      Mass, Systolic/Diastolic Blood Pressure, Heart Rate, Hematocrit, Flow Time
      Corrected and Water Balance Index between the two groups. In contrast, higher
      values of the Cardiac Output, Stroke Volume, Fat Mass and Inotropy Index have
      been highlighted in the Group A. Moreover, in the Group A we found a better
      maternal-neonatal outcome and a lower incidence of hypertensive complications.
      CONCLUSIONS: High TVR during the first weeks of gestation may be an early marker
      of cardiovascular maladaptation more than the evaluation of water distribution
      and, in particular, with respect to the single blood pressure assessment.
      Moreover lower values of Inotropy Index could be an indicative of the worst
      cardiac performance.

PMID- 25943645
TI  - Pre-eclampsia causes adverse maternal outcomes across the gestational spectrum.
AB  - OBJECTIVE: To determine if women with early onset pre-eclampsia (EOP) have worse
      maternal outcomes than those who present later. Specifically, we aimed to
      determine whether term preeclamptic women and their infants have better outcomes
      than either their late pre-term or early onset counterparts. STUDY DESIGN:
      Between 1991 and 2011, 4657 pregnancies complicated by hypertension were recorded
      in our database; 2148 (45%) had pre-eclampsia (PE). Six hundred ninety six cases
      (32%) that had accurate data for the gestation at which PE developed were
      analysed. Pre-eclampsia was defined as per the International Society for the
      Study of Hypertension in Pregnancy guidelines. Maternal outcomes included (1)
      episodes of severe hypertension, (2) proteinuria, (3) acute kidney injury, (4)
      abnormal liver function, (5) thrombocytopenia and (6) neurological complications.
      Perinatal outcomes were also analysed. RESULTS: Eighty seven (13%) of 696 cases
      had EOP; 226 (32%) had late pre-term PE and 383 (55%) term PE. Maternal age was
      similar amongst the three groups. Women with late pre-term and term PE had
      similar rates of maternal and foetal outcomes. Compared with term PE, women with
      EOP had similar rates of adverse maternal outcomes, however their babies had
      significantly increased rates of morbidity and mortality. CONCLUSION: Pre
      eclampsia causes significant maternal organ involvement regardless of gestation
      at onset. Outcomes for babies of women with EOP are significantly worse than for
      those who present later. Overall, women presenting with PE after 34 weeks have
      generally good maternal and foetal outcomes in a unit equipped to manage such
      cases.

PMID- 25943646
TI  - Positive correlations between circulating adiponectin and MMP2 in preeclampsia
      pregnant.
AB  - OBJECTIVE: The aims of the present study were to compare plasma concentrations of
      the adiponectin, leptin, metalloproteinases (MMP9 and MMP2) and its tissue
      inhibitors (TIMP1 and TIMP2) in preeclamptic (PE) and healthy pregnant (HP)
      groups and correlate them. METHODS: A total of 105 pregnant women with pre
      pregnancy body mass index (BMI) values ? 30 kg/m(2) were enrolled for this study
      (59 PE and 46 HP). Biomarkers were measured using ELISAs. RESULTS: Adiponectin
      (32%), leptin (45%), MMP2 (20%), TIMP1 (31%) and TIMP2 (23%) levels were higher
      in PE compared to HP (all P < 0.05). In addition there were positive correlations
      between adiponectin and MMP2 (r = 0.33; P = 0.03) and adiponectin and TIMP2 (r =
      0.33; P = 0.03) in PE group, but not in HP. CONCLUSION: Our findings show that
      adiponectin, leptin, MMP2, TIMP1 and TIMP2 levels are increased in PE and
      adiponectin may contribute to higher levels of MMP2 and TIMP2 in this disease.

PMID- 25943647
TI  - Folic acid causes higher prevalence of detectable unmetabolized folic acid in
      serum than B-complex: a randomized trial.
AB  - PURPOSE: Unmetabolized folic acid (UMFA) is common in serum of elderly
      individuals receiving folic acid (FA)-fortified foods or supplements. We studied
      the effect of supplementing FA or B-complex on serum concentrations of (6S)-5
      methyltetrahydropteroylglutamate [(6S)-5-CH3-H4Pte] and UMFA in elderly people
      and explored factors associated with detectable UMFA post-supplementation.
      METHODS: This is a randomized single-blind non-controlled trial on 58 elderly
      people using daily 400 ug FA (n = 31) or 400 ug FA, 10 ug cyanocob(III)alamin and
      8 mg pyridoxine (n = 27) for a median of 23 days. Main outcome includes changes
      in concentrations of serum (6S)-5-CH3-H4Pte and UMFA. RESULTS: Total homocysteine
      declined by a median of 1.6 (p = 0.074) in the FA and 1.3 umol/L (p = 0.009) in
      the B-complex arms (p = 0.66 between the arms). Serum (6S)-5-CH3-H4Pte
      significantly (p < 0.001 vs. baseline) increased by a median of 9.2 and 6.5
      nmol/L in the FA and B-complex groups, respectively (p = 0.152 between the
      groups). Compared to FA, B-complex reduced cystathionine and caused lower post
      intervention serum UMFA, percentage of UMFA to (6S)-5-CH3-H4Pte and prevalence of
      UMFA >= 0.21 nmol/L. Higher serum cystathionine and whole-blood folate predicted
      higher post-intervention serum UMFA. CONCLUSIONS: FA caused higher UMFA as
      compared to B-complex. Pyridoxine appears to improve folate recycling. Data on
      serum UMFA should be interpreted in relation to other vitamins involved in folate
      metabolism. Serum UMFA is suggested to play a sensory role through which the cell
      recognizes FA available for metabolism via dihydrofolate reductase.

PMID- 25943648
TI  - Urinary phytoestrogens and cancer, cardiovascular, and all-cause mortality in the
      continuous National Health and Nutrition Examination Survey.
AB  - PURPOSE: Experimental studies suggest that phytoestrogen intake alters cancer and
      cardiovascular risk. This study investigated the associations of urinary
      phytoestrogens with total cancer (n = 79), cardiovascular (n = 108), and all
      cause (n = 290) mortality among 5179 participants in the continuous National
      Health and Nutrition Examination Survey (1999-2004). METHODS: Urinary
      phytoestrogens were measured using high-performance liquid chromatography with
      tandem mass spectrometric detection. Survival analysis was performed to evaluate
      hazard ratios (HRs) and 95 % confidence intervals (CIs) for each of the three
      outcomes in relation to urinary phytoestrogens. RESULTS: After adjustment for
      confounders, higher urinary concentrations of total enterolignans were associated
      with a reduced risk of death from cardiovascular disease (HR for tertile 3 vs.
      tertile 1 0.48; 95 % CI 0.24, 0.97), whereas higher urinary concentrations of
      total isoflavones (HR for tertile 3 vs. tertile 1 2.14; 95 % CI 1.03, 4.47) and
      daidzein (HR for tertile 3 vs. tertile 1 2.05; 95 % CI 1.02, 4.11) were
      associated with an increased risk. A reduction in all-cause mortality was
      observed for elevated urinary concentrations of total enterolignans (HR for
      tertile 3 vs. tertile 1 0.65; 95 % CI 0.43, 0.96) and enterolactone (HR for
      tertile 3 vs. tertile 1 0.65; 95 % CI 0.44, 0.97). CONCLUSIONS: Some urinary
      phytoestrogens were associated with cardiovascular and all-cause mortality in a
      representative sample of the US population. This is one of the first studies that
      used urinary phytoestrogens as biomarkers of their dietary intake to evaluate the
      effect of these bioactive compounds on the risk of death from cancer and
      cardiovascular disease.

PMID- 25943651
TI  - Training and competing in the heat.

PMID- 25943649
TI  - Fasting for 3 days during the suckling-weaning transient period in male rats
      induces metabolic abnormalities in the liver and is associated with impaired
      glucose tolerance in adulthood.
AB  - PURPOSE: Recent studies suggest that nutritional status during developmental
      periods is associated with subsequent development of metabolic abnormalities. In
      this study, we examined whether malnutrition by fasting for 3 days during the
      suckling-weaning transient period induces subsequent development of metabolic
      abnormalities in rats. METHODS: Male Sprague-Dawley rats were fasted for 3 days
      during the suckling-weaning transient period. They are subsequently fed a high
      fat, high-sucrose (HF) or low-fat, high-starch (LF) diet for 14 weeks from 17
      weeks of age, and the liver and blood samples were collected for measuring mRNA
      and protein levels of metabolic genes and blood concentrations of glucose and
      insulin, respectively. RESULTS: Fasting for 3 days during the suckling-weaning
      transient period induced impaired glucose tolerance in rats fed the LF diet in
      adulthood. Liver triglycerides in rats fed the HF diet in adulthood increased to
      140 % in rats fasted for 3 days during the suckling-weaning transient period
      compared with those non-fasted. Furthermore, liver expression of FBP1 and
      ACCalpha genes in adult rats fed the LF diet increased to 125 and 145 %,
      respectively, in rats fasted for 3 days during the suckling-weaning transient
      period compared to non-fasted rats. PEPCK1 protein expression levels in rats fed
      the LF diet were higher in rats fasted for 3 days during the suckling-weaning
      transient period than in non-fasted rats. CONCLUSION: Fasting for 3 days in rats
      during the suckling-weaning transient period enhances metabolic abnormalities in
      animals fed a HF or LF diet in adulthood by confounding metabolism of lipid and
      sugar in the liver.

PMID- 25943652
TI  - Critical core temperature: a hypothesis too simplistic to explain hyperthermia
      induced fatigue.

PMID- 25943653
TI  - Consensus recommendations on training and competing in the heat.
AB  - Exercising in the heat induces thermoregulatory and other physiological strain
      that can lead to impairments in endurance exercise capacity. The purpose of this
      consensus statement is to provide up-to-date recommendations to optimize
      performance during sporting activities undertaken in hot ambient conditions. The
      most important intervention one can adopt to reduce physiological strain and
      optimize performance is to heat acclimatize. Heat acclimatization should comprise
      repeated exercise-heat exposures over 1-2 weeks. In addition, athletes should
      initiate competition and training in a euhydrated state and minimize dehydration
      during exercise. Following the development of commercial cooling systems (e.g.,
      cooling vest), athletes can implement cooling strategies to facilitate heat loss
      or increase heat storage capacity before training or competing in the heat.
      Moreover, event organizers should plan for large shaded areas, along with cooling
      and rehydration facilities, and schedule events in accordance with minimizing the
      health risks of athletes, especially in mass participation events and during the
      first hot days of the year. Following the recent examples of the 2008 Olympics
      and the 2014 FIFA World Cup, sport governing bodies should consider allowing
      additional (or longer) recovery periods between and during events for hydration
      and body cooling opportunities when competitions are held in the heat. 

PMID- 25943654
TI  - Adaptations and mechanisms of human heat acclimation: Applications for
      competitive athletes and sports.
AB  - Exercise heat acclimation induces physiological adaptations that improve
      thermoregulation, attenuate physiological strain, reduce the risk of serious heat
      illness, and improve aerobic performance in warm-hot environments and potentially
      in temperate environments. The adaptations include improved sweating, improved
      skin blood flow, lowered body temperatures, reduced cardiovascular strain,
      improved fluid balance, altered metabolism, and enhanced cellular protection. The
      magnitudes of adaptations are determined by the intensity, duration, frequency,
      and number of heat exposures, as well as the environmental conditions (i.e., dry
      or humid heat). Evidence is emerging that controlled hyperthermia regimens where
      a target core temperature is maintained, enable more rapid and complete
      adaptations relative to the traditional constant work rate exercise heat
      acclimation regimens. Furthermore, inducing heat acclimation outdoors in a
      natural field setting may provide more specific adaptations based on direct
      exposure to the exact environmental and exercise conditions to be encountered
      during competition. This review initially examines the physiological adaptations
      associated with heat acclimation induction regimens, and subsequently emphasizes
      their application to competitive athletes and sports. 

PMID- 25943655
TI  - The role of fluid temperature and form on endurance performance in the heat.
AB  - Exercising in the heat often results in an excessive increase in body core
      temperature, which can be detrimental to health and endurance performance.
      Research in recent years has shifted toward the optimum temperature at which
      drinks should be ingested. The ingestion of cold drinks can reduce body core
      temperature before exercise but less so during exercise. Temperature of drinks
      does not seem to have an effect on the rate of gastric emptying and intestinal
      absorption. Manipulating the specific heat capacity of a solution can further
      induce a greater heat sink. Ingestion of ice slurry exploits the additional
      energy required to convert the solution from ice to water (enthalpy of fusion).
      Body core temperature is occasionally observed to be higher at the point of
      exhaustion with the ingestion of ice slurry. There is growing evidence to suggest
      that ingesting ice slurry is an effective and practical strategy to prevent
      excessive rise of body core temperature and improve endurance performance. This
      information is especially important when only a fixed amount of fluid is allowed
      to be carried, often seen in some ultra-endurance events and military operations.
      Future studies should evaluate the efficacy of ice slurry in various exercise and
      environmental conditions. 

PMID- 25943656
TI  - Human behavioral thermoregulation during exercise in the heat.
AB  - The human capacity to perform prolonged exercise is impaired in hot environments.
      To address this issue, a number of studies have investigated behavioral aspects
      of thermoregulation that are recognized as important factors in determining
      performance. In this review, we evaluated and interpreted the available knowledge
      regarding the voluntary control of exercise work rate in hot environments. Our
      analysis indicated that: (a) Voluntary reductions in exercise work rate in
      uncompensable heat aid thermoregulation and are, therefore, thermoregulatory
      behaviors. (b) Unlike thermal behavior during rest, the role of thermal comfort
      as the ultimate mediator of thermal behavior during exercise in the heat remains
      uncertain. By contrast, the rating of perceived exertion appears to be the key
      perceptual controller under such conditions, with thermal perception playing a
      more modulatory role. (c) Prior to increases in core temperature (when only skin
      temperature is elevated), reductions in self-selected exercise work rate in the
      heat are likely mediated by thermal perception (thermal comfort and sensation)
      and its influence on the rating of perceived exertion. (d) However, when both
      core and skin temperatures are elevated, factors associated with cardiovascular
      strain likely dictate the rate of perceived exertion response, thereby mediating
      such voluntary reductions in exercise work rate. 

PMID- 25943657
TI  - Neurophysiological effects of exercise in the heat.
AB  - Fatigue during prolonged exercise is a multifactorial phenomenon. The complex
      interplay between factors originating from both the periphery and the brain will
      determine the onset of fatigue. In recent years, electrophysiological and imaging
      tools have been fine-tuned, allowing for an improved understanding of what
      happens in the brain. In the first part of the review, we present literature that
      studied the changes in electrocortical activity during and after exercise in
      normal and high ambient temperature. In general, exercise in a thermo-neutral
      environment or at light to moderate intensity increases the activity in the beta
      frequency range, while exercising at high intensity or in the heat reduces beta
      activity. In the second part, we review literature that manipulated brain
      neurotransmission, through either pharmacological or nutritional means, during
      exercise in the heat. The dominant outcomes were that manipulations changing
      brain dopamine concentration have the potential to delay fatigue, while the
      manipulation of serotonin had no effect and noradrenaline reuptake inhibition was
      detrimental for performance in the heat. Research on the effects of
      neurotransmitter manipulations on brain activity during or after exercise is
      scarce. The combination of brain imaging techniques with electrophysiological
      measures presents one of the major future challenges in exercise
      physiology/neurophysiology. 

PMID- 25943658
TI  - Sprint performance under heat stress: A review.
AB  - Training and competition in major track-and-field events, and for many team or
      racquet sports, often require the completion of maximal sprints in hot (>30 
      degrees C) ambient conditions. Enhanced short-term (<30 s) power output or single
      sprint performance, resulting from transient heat exposure (muscle temperature
      rise), can be attributed to improved muscle contractility. Under heat stress,
      elevations in skin/core temperatures are associated with increased cardiovascular
      and metabolic loads in addition to decreasing voluntary muscle activation; there
      is also compelling evidence to suggest that large performance decrements occur
      when repeated-sprint exercise (consisting of brief recovery periods between
      sprints, usually <60 s) is performed in hot compared with cool conditions.
      Conversely, poorer intermittent-sprint performance (recovery periods long enough
      to allow near complete recovery, usually 60-300 s) in hotter conditions is solely
      observed when exercise induces marked hyperthermia (core temperature >39  degrees
      C). Here we also discuss strategies (heat acclimatization, precooling, hydration
      strategies) employed by "sprint" athletes to mitigate the negative influence of
      higher environmental temperatures. 

PMID- 25943659
TI  - Exercise intensity prescription during heat stress: A brief review.
AB  - Exercise intensity can be prescribed using a variety of indices, such as rating
      of perceived exertion, heart rate, levels of absolute intensity (e.g., metabolic
      equivalents), and levels of relative intensity [e.g., percentage of maximal
      aerobic capacity (% V  O 2 m a x ) or percentage of oxygen uptake reserve (% V  O
      2 R )]. Heart rate has a linear relationship with oxygen uptake, is easy to
      measure, and requires relatively inexpensive monitoring equipment, so it is
      commonly used to monitor exercise intensity. During heat stress, however,
      cardiovascular adjustments - including a rise in heart rate that is
      disproportionate to absolute intensity - result in diminished aerobic capacity
      and performance. These adjustments include cardiovascular drift, the progressive
      rise in heart rate and fall in stroke volume over time during prolonged, constant
      rate exercise. A variety of factors have been shown to modulate the magnitude of
      cardiovascular drift, e.g., hyperthermia, dehydration, exercise intensity, and
      ambient temperature. Regardless of the mode of manipulation, decreases in stroke
      volume with cardiovascular drift are associated with proportionally similar
      decreases in V  O 2 m a x , which affects the relationship between heart rate and
      relative metabolic intensity (% V  O 2 m a x or % V  O 2 R ). This review
      summarizes the current state of knowledge regarding the influence of
      cardiovascular drift and reduced V  O 2 m a x on exercise intensity prescription
      in hot conditions. 

PMID- 25943660
TI  - Acute acetaminophen ingestion does not alter core temperature or sweating during
      exercise in hot-humid conditions.
AB  - Acute acetaminophen (ACT) ingestion has been reported to reduce thermal strain
      during cycling in the heat. In this study, nine active participants ingested 20
      mg of ACT per kg of total body mass (ACT) or a placebo (PLA), 60 min prior to
      cycling at a fixed rate of metabolic heat production (ACT: 8.3 +/- 0.3 W/kg; PLA:
      8.5 +/- 0.5 W/kg), which was equivalent to 55 +/- 6% VO2max , for 60 min at 34.5
      +/- 0.1  degrees C, 52 +/- 1% relative humidity. Resting rectal temperature (Tre
      ; ACT: 36.70 +/- 0.17  degrees C; PLA: 36.80 +/- 0.16  degrees C, P = 0.24),
      esophageal temperature (Tes ; ACT: 36.54 +/- 0.22  degrees C; PLA: 36.61 +/- 0.17
      degrees C, P = 0.50) and mean skin temperature (Tsk ; ACT: 34.00 +/- 0.14 
      degrees C; PLA: 33.96 +/- 0.20  degrees C, P = 0.70) were all similar among
      conditions. At end-exercise, no differences in DeltaTre (ACT: 1.12 +/- 0.15 
      degrees C; PLA: 1.11 +/- 0.21  degrees C, P = 0.92), DeltaTes (ACT: 0.90 +/- 0.28
      degrees C; PLA: 0.88 +/- 0.23  degrees C, P = 0.84), DeltaTsk (ACT: 0.80 +/-
      0.39  degrees C; PLA: 0.70 +/- 0.46  degrees C, P = 0.63), mean local sweat rate
      (ACT: 1.02 +/- 0.15 mg/cm(2) /min; PLA: 1.02 +/- 0.13 mg/cm(2) /min, P = 0.98)
      and whole-body sweat loss (ACT: 663 +/- 83 g; PLA: 663 +/- 77 g, P = 0.995) were
      evident. Furthermore, ratings of perceived exertion and thermal sensation and
      thermal comfort were not different between ACT and PLA conditions. In conclusion,
      ACT ingested 60 min prior to moderate intensity exercise in hot-humid conditions
      does not alter physiologic thermoregulatory control nor perceived strain. 

PMID- 25943661
TI  - Separate and combined effects of dehydration and thirst sensation on exercise
      performance in the heat.
AB  - Using intravenous infusion, we separated the physiologic consequences of 3% body
      mass dehydration from the conscious awareness of fluid replacement on time trial
      (TT) performance in the heat. Eleven trained cyclists performed 90 min of steady
      state (50% V  O 2 peak ) cycling followed by a self-paced 20-km TT in a hot-dry
      (35  degrees C, 10% relative humidity, wind speed 3.0 m/s) environment while
      euhydrated-not thirsty (EU-NT), euhydrated-thirsty (EU-T), dehydrated-not thirsty
      (DH-NT), or dehydrated-thirsty (DH-T). Thirst was manipulated by providing (NT)
      or withholding (T) ad libitum 35  degrees C water oral rinse. Distinct hydration
      states existed, with 0.4 +/- 0.5% dehydration following the 20-km TT (EU)
      compared with 3.2 +/- 0.6% in DH (P < 0.001). Greater perceived thirst existed in
      T (7 +/- 2 on a 1-9 scale) than NT (4 +/- 2, P < 0.001) after the TT. No
      significant differences in power output existed during the TT between hydration
      (EU 202.9 +/- 36.5 W vs DH 207.0 +/- 35.9 W, P = 0.362) and thirst conditions (NT
      203.3 +/- 35.6 W vs T 206.6 +/- 36.8 W, P = 0.548), nor were there differences in
      completion time (P = 0.832) or pacing profile (P = 0.690). Within the range of up
      to 3% body mass loss, neither the physiologic effects from lowered hydration
      status nor the perception of thirst, separately or combined, affected sustained
      submaximal exercise performance in the heat for a healthy and fit population. 

PMID- 25943662
TI  - Hydration and endocrine responses to intravenous fluid and oral glycerol.
AB  - Athletes use intravenous (IV) saline in an attempt to maximize rehydration. The
      diuresis from IV rehydration may be circumvented through the concomitant use of
      oral glycerol. We examined the effects of rehydrating with differing regimes of
      oral and IV fluid, with or without oral glycerol, on hydration, urine, and
      endocrine indices. Nine endurance-trained men were dehydrated by 4% bodyweight,
      then rehydrated with 150% of the fluid lost via four protocols: (a) oral = oral
      fluid only; (b) oral glycerol = oral fluid with added glycerol (1.5 g/kg); (c) IV
      = 50% IV fluid, 50% oral fluid; and (d) IV with oral glycerol = 50% IV fluid, 50%
      oral fluid with added glycerol (1.5 g/kg), using a randomized, crossover design.
      They then completed a cycling performance test. Plasma volume restoration was
      highest in IV with oral glycerol > IV > oral glycerol  > oral. Urine volume was
      reduced in both IV trials compared with oral. IV and IV with oral glycerol
      resulted in lower aldosterone levels during rehydration and performance, and
      lower cortisol levels during rehydration. IV with oral glycerol resulted in the
      greatest fluid retention. In summary, the IV conditions resulted in greater fluid
      retention compared with oral and lower levels of fluid regulatory and stress
      hormones compared with both oral conditions. 

PMID- 25943663
TI  - Hyperthermia, but not muscle water deficit, increases glycogen use during intense
      exercise.
AB  - We determined if dehydration alone or in combination with hyperthermia
      accelerates muscle glycogen use during intense exercise. Seven endurance-trained
      cyclists (VO2max  = 54.4 +/- 1.05 mL/kg/min) dehydrated 4.6% of body mass (BM)
      during exercise in the heat (150 min at 33 +/- 1  degrees C, 25 +/- 2% humidity).
      During recovery (4 h), subjects remained dehydrated (HYPO trial) or recovered all
      fluid losses (REH trials). Finally, subjects exercised intensely (75% VO2max )
      for 40 min in a neutral (25 +/- 1  degrees C; HYPO and REH trials) or in a hot
      environment (36 +/- 1  degrees C; REHHOT ). Before the final exercise bout vastus
      lateralis glycogen concentration was similar in all three trials (434 +/- 57
      mmol/kg of dry muscle (dm)) but muscle water content was lower in the HYPO (357
      +/- 14 mL/100 g dm) than in REH trials (389 +/- 25 and 386 +/- 25 mL/100 g dm; P
      < 0.05). After 40 min of intense exercise, intestinal temperature was similar
      between the HYPO and REHHOT trials (39.2 +/- 0.5 and 39.2 +/- 0.4  degrees C,
      respectively) and glycogen use was similar (172 +/- 86 and 185 +/- 97 mmol/kg dm,
      respectively) despite large differences in muscle water content. In contrast,
      during REH, intestinal temperature (38.5 +/- 0.4  degrees C) and glycogen use
      (117 +/- 52 mmol/kg dm) were significantly lower than during HYPO and REHHOT .
      Our data suggest that hyperthermia stimulates glycogen use during intense
      exercise while muscle water deficit has a minor role. 

PMID- 25943664
TI  - Heat stress exacerbates the reduction in middle cerebral artery blood velocity
      during prolonged self-paced exercise.
AB  - This study examined the influence of hyperthermia on middle cerebral artery mean
      blood velocity (MCA Vmean). Eleven cyclists undertook a 750 kJ self-paced time
      trial in HOT (35  degrees C) and COOL (20  degrees C) conditions. Exercise time
      was longer in HOT (56 min) compared with COOL (49 min; P < 0.001). Power output
      in HOT was significantly lower from 40% of work completed onward (P < 0.01).
      Rectal temperature increased to 39.6 +/- 0.6  degrees C (HOT) and 38.8 +/- 0.5 
      degrees C (COOL; P < 0.01). Skin temperature, skin blood flow, and heart rate
      were higher throughout HOT compared with COOL (P < 0.05). A similar increase in
      ventilation (P < 0.05) and decrease in end-tidal partial pressure of CO2 (PETCO2
      ; P < 0.05) occurred in both conditions. Arterial blood pressure and oxygen
      uptake were lower from 50% of work completed onward in HOT compared with COOL (P
      < 0.01). MCA Vmean increased at 10% in both conditions (P < 0.01), decreasing
      thereafter (P < 0.01) and to a greater extent in HOT from 40% of work completed
      onward (P < 0.05). Therefore, despite a comparable ventilatory response and
      PETCO2 in the HOT and COOL conditions, the greater level of thermal strain
      developing in the heat appears to have exacerbated the reduction in MCA Vmean, in
      part via increases in peripheral blood flow and a decrease in arterial blood
      pressure. 

PMID- 25943665
TI  - Restoring heat stress-associated reduction in middle cerebral artery velocity
      does not reduce fatigue in the heat.
AB  - Heat-induced hyperventilation may reduce PaCO2 and thereby cerebral perfusion and
      oxygenation and in turn exercise performance. To test this hypothesis, eight
      volunteers completed three incremental exercise tests to exhaustion: (a) 18 
      degrees C ambient temperature (CON); (b) 38  degrees C (HEAT); and (c) 38 
      degrees C with addition of CO2 to inspiration to prevent the hyperventilation
      induced reduction in PaCO2 (HEAT + CO2 ). In HEAT and HEAT + CO2 , rectal
      temperature was elevated prior to the exercise tests by means of hot water
      submersion and was higher (P < 0.05) than in CON. Compared with CON, ventilation
      was elevated (P < 0.01), and hence, PaCO2 reduced in HEAT. This caused a
      reduction (P < 0.05) in mean cerebral artery velocity (MCAvmean ) from 68.6 +/-
      15.5 to 53.9 +/- 10.0 cm/s, which was completely restored in HEAT + CO2 (68.8 +/-
      5.8 cm/s). Cerebral oxygenation followed a similar pattern. V  O 2   m a x was
      4.6 +/- 0.1 L/min in CON and decreased (P < 0.05) to 4.1 +/- 0.2 L/min in HEAT
      and remained reduced in HEAT + CO2 (4.1 +/- 0.2 L/min). Despite normalization of
      MCAvmean and cerebral oxygenation in HEAT + CO2 , this did not improve exercise
      performance, and thus, the reduced MCAvmean in HEAT does not seem to limit
      exercise performance. 

PMID- 25943666
TI  - Plantar flexor neuromuscular adjustments following match-play football in hot and
      cool conditions.
AB  - We assessed neuromuscular fatigue and recovery of the plantar flexors after
      playing football with or without severe heat stress. Neuromuscular
      characteristics of the plantar flexors were assessed in 17 male players at
      baseline and ~30 min, 24, and 48 h after two 90-min football matches in temperate
      (~20  degrees C and 55% rH) and hot (~43  degrees C and 20% rH) environments.
      Measurements included maximal voluntary strength, muscle activation, twitch
      contractile properties, and rate of torque development and soleus EMG (i.e., root
      mean square activity) rise from 0 to 30, -50, -100, and -200 ms during maximal
      isometric contractions for plantar flexors. Voluntary activation and peak twitch
      torque were equally reduced (-1.5% and -16.5%, respectively; P < 0.05) post
      matches relative to baseline in both conditions, the latter persisting for at
      least 48 h, whereas strength losses (~5%) were not significant. Absolute
      explosive force production declined (P < 0.05) 30 ms after contraction onset
      independently of condition, with no change at any other epochs. Globally,
      normalized rate of force development and soleus EMG activity rise values remained
      unchanged. In football, match-induced alterations in maximal and rapid torque
      production capacities of the plantar flexors are moderate and do not differ after
      competing in temperate and hot environments. 

PMID- 25943667
TI  - Augmented supraspinal fatigue following constant-load cycling in the heat.
AB  - The development of central fatigue is prominent following exercise-induced
      hyperthermia, but the contribution of supraspinal fatigue is not well understood.
      Seven endurance-trained cyclists (mean +/- SD peak O2 uptake, 62.0 +/- 5.6
      mL/kg/min) completed two high-intensity constant-load cycling trials (296 +/- 34
      W) to the limit of tolerance in a hot (34  degrees C, 20% relative humidity) and,
      on a separate occasion, for the same duration, a control condition (18  degrees
      C, 20% relative humidity). Core body temperature (Tc ) was measured throughout.
      Before and immediately after each trial, twitch responses to supramaximal femoral
      nerve and transcranial magnetic stimulation were obtained from the knee extensors
      to assess neuromuscular and corticospinal function, respectively. Exercise time
      was 11.4 +/- 2.6 min. Peak Tc was higher in the hot compared with control (38.36
      +/- 0.43  degrees C vs 37.86 +/- 0.36  degrees C; P = 0.035). Post-exercise
      reductions in maximal voluntary contraction force (13 +/- 9% vs 9 +/- 5%),
      potentiated twitch force (16 +/- 12% vs 21 +/- 13%) and voluntary activation (9
      +/- 7% vs 7 +/- 7%) were similar in hot and control trials, respectively.
      However, cortical voluntary activation declined more in the hot compared with the
      control (8 +/- 3% vs 3 +/- 2%; P = 0.001). Exercise-induced hyperthermia elicits
      significant central fatigue of which a large portion can be attributed to
      supraspinal fatigue. These data indicate that performance decrements in the heat
      might initially originate in the brain. 

PMID- 25943668
TI  - Influence of exercise training with thigh compression on heat-loss responses.
AB  - We investigated the effect of thigh compression, which accelerates activation of
      central command and muscle metabo- and mechanoreceptors, on the adaptation of
      sweating and cutaneous vascular responses during exercise heat acclimation. Nine
      non-heat-acclimated male subjects were acclimated to heat (32  degrees C and 50%
      RH) while cycling [50% of maximum oxygen uptake ( V  O 2 m a x )] 60 min/day for
      7 days (control group). The experimental group (n = 9) conducted the same
      training while the proximal thighs were compressed by a cuff at 60 mmHg. V  O 2 m
      a x , acetylcholine-induced forearm sweating rate (iontophoresis), and mean
      sweating and cutaneous vascular responses on the forehead, chest, and forearm
      (SRmean and CVCmean ) during passive heating were evaluated before and after
      training. Training significantly increased V  O 2 m a x while did not affect
      acetylcholine-induced sweating rates in either group. Training significantly
      decreased Tb thresholds for SRmean and CVCmean during passive heating without the
      alternations of sensitivities in both groups. Although SRmean during passive
      heating at a given DeltaTb was not improved in either group, CVCmean was
      significantly (P < 0.05) attenuated after exercise training only in experimental
      group. Our results indicate that thigh cuff compression during exercise heat
      acclimation does not influence adaptation of the sweating response but attenuate
      cutaneous vasodilation. 

PMID- 25943669
TI  - Conductive and evaporative precooling lowers mean skin temperature and improves
      time trial performance in the heat.
AB  - Self-paced endurance performance is compromised by moderate-to-high ambient
      temperatures that are evident in many competitive settings. It has become common
      place to implement precooling prior to competition in an attempt to alleviate
      perceived thermal load and performance decline. The present study aimed to
      investigate precooling incorporating different cooling avenues via either
      evaporative cooling alone or in combination with conductive cooling on cycling
      time trial performance. Ten trained male cyclists completed a time trial on three
      occasions in hot (35  degrees C) ambient conditions with the cooling garment
      prepared by (a) immersion in water (COOL, evaporative); (b) immersion in water
      and frozen (COLD, evaporative and conductive); or (c) no precooling (CONT). COLD
      improved time trial performance by 5.8% and 2.6% vs CONT and COOL, respectively
      (both P < 0.05). Power output was 4.5% higher for COLD vs CONT (P < 0.05). Mean
      skin temperature was lower at the onset of the time trial following COLD compared
      with COOL and CONT (both P < 0.05) and lasted for the first 20% of the time
      trial. Thermal sensation was perceived cooler following COOL and COLD. The
      combination of evaporative and conductive cooling (COLD) had the greatest benefit
      to performance, which is suggested to be driven by reduced skin temperature
      following cooling. 

PMID- 25943670
TI  - Physiological responses to incremental exercise in the heat following internal
      and external precooling.
AB  - Twelve males completed three incremental, discontinuous treadmill tests in the
      heat [31.9(1.0)  degrees C, 61.9(8.9)%] to determine speed at two fixed blood
      lactate concentrations (2 and 3.5 mmol/L), running economy (RE), and maximum
      oxygen uptake ( V  O 2 m a x ). Trials involved 20 min of either internal cooling
      (ICE, 7.5 g/kg ice slurry ingestion) or mixed-methods external cooling (EXT, cold
      towels, forearm immersion, ice vest, and cooling shorts), alongside no
      intervention (CON). Following precooling, participants ran 0.3 km/h faster at 2
      mmol/L and 0.2 km/h faster at 3.5 mmol/L (P = 0.04, partial eta(2)  = 0.27).
      Statistical differences were observed vs CON for ICE (P = 0.03, d = 0.15), but
      not EXT (P = 0.12, d = 0.15). There was no effect of cooling on RE (P = 0.81,
      partial eta(2)  = 0.02), nor on V  O 2 m a x (P = 0.69, partial eta(2)  = 0.04).
      An effect for cooling on physiological strain index was observed (P < 0.01,
      partial eta(2)  = 0.41), with differences vs CON for EXT (P = 0.02, d = 0.36),
      but not ICE (P = 0.06, d = 0.36). Precooling reduced thermal sensation (P < 0.01,
      partial eta(2)  = 0.66) in both cooling groups (P < 0.01). Results indicate ICE
      and EXT provide similar physiological responses for exercise up to 30 min
      duration in the heat. Differing thermoregulatory responses are suggestive of
      specific event characteristics determining the choice of cooling. Precooling
      appears to reduce blood lactate accumulation and reduce thermoregulatory and
      perceptual strain during incremental exercise. 

PMID- 25943671
TI  - Mild evaporative cooling applied to the torso provides thermoregulatory benefits
      during running in the heat.
AB  - We investigated the effects of mild evaporative cooling applied to the torso,
      before or during running in the heat. Nine male participants performed three
      trials: control-no cooling (CTR), pre-exercise cooling (PRE-COOL), and during
      exercise cooling (COOL). Trials consisted of 10-min neutral exposure and 50-min
      heat exposure (30  degrees C; 44% humidity), during which a 30-min running
      protocol (70% VO2max ) was performed. An evaporative cooling t-shirt was worn
      before the heat exposure (PRE-COOL) or 15 min after the exercise was started
      (COOL). PRE-COOL significantly lowered local skin temperature (Tsk ) (up to -5.3
      +/- 0.3  degrees C) (P < 0.001), mean Tsk (up to -2 +/- 0.1  degrees C) (P <
      0.001), sweat losses (-143 +/- 40 g) (P = 0.002), and improved thermal comfort (P
      = 0.001). COOL suddenly lowered local Tsk (up to -3.8 +/- 0.2  degrees C) (P <
      0.001), mean Tsk (up to -1 +/- 0.1  degrees C) (P < 0.001), heart rate (up to -11
      +/- 2 bpm) (P = 0.03), perceived exertion (P = 0.001), and improved thermal
      comfort (P = 0.001). We conclude that the mild evaporative cooling provided
      significant thermoregulatory benefits during exercise in the heat. However, the
      timing of application was critical in inducing different thermoregulatory
      responses. These findings provide novel insights on the thermoregulatory role of
      Tsk during exercise in the heat. 

PMID- 25943673
TI  - Low-frequency electrical stimulation combined with a cooling vest improves
      recovery of elite kayakers following a simulated 1000-m race in a hot
      environment.
AB  - This study compared the effects of a low-frequency electrical stimulation (LFES;
      Veinoplus((r)) Sport, Ad Rem Technology, Paris, France), a low-frequency
      electrical stimulation combined with a cooling vest (LFESCR ) and an active
      recovery combined with a cooling vest (ACTCR ) as recovery strategies on
      performance (racing time and pacing strategies), physiologic and perceptual
      responses between two sprint kayak simulated races, in a hot environment (~32 wet
      bulb-globe temperature). Eight elite male kayakers performed two successive 1000
      m kayak time trials (TT1 and TT2), separated by a short-term recovery period,
      including a 30-min of the respective recovery intervention protocol, in a
      randomized crossover design. Racing time, power output, and stroke rate were
      recorded for each time trial. Blood lactate concentration, pH, core, skin and
      body temperatures were measured before and after both TT1 and TT2 and at mid- and
      post-recovery intervention. Perceptual ratings of thermal sensation were also
      collected. LFESCR was associated with a very likely effect in performance
      restoration compared with ACTCR (99/0/1%) and LFES conditions (98/0/2%). LFESCR
      induced a significant decrease in body temperature and thermal sensation at post
      recovery intervention, which is not observed in ACTCR condition. In conclusion,
      the combination of LFES and wearing a cooling vest (LFESCR ) improves performance
      restoration between two 1000-m kayak time trials achieved by elite athletes, in
      the heat. 

PMID- 25943672
TI  - Relieving thermal discomfort: Effects of sprayed L-menthol on perception,
      performance, and time trial cycling in the heat.
AB  - L-menthol stimulates cutaneous thermoreceptors and induces cool sensations
      improving thermal comfort, but has been linked to heat storage responses; this
      could increase risk of heat illness during self-paced exercise in the heat.
      Therefore, L-menthol application could lead to a discrepancy between behavioral
      and autonomic thermoregulatory drivers. Eight male participants volunteered. They
      were familiarized and then completed two trials in hot conditions (33.5  degrees
      C, 33% relative humidity) where their t-shirt was sprayed with CONTROL-SPRAY or
      MENTHOL-SPRAY after 10 km (i.e., when they were hot and uncomfortable) of a 16.1
      km cycling time trial (TT). Thermal perception [thermal sensation (TS) and
      comfort (TC)], thermal responses [rectal temperature (Trec ), skin temperature
      (Tskin )], perceived exertion (RPE), heart rate, pacing (power output), and TT
      completion time were measured. MENTHOL-SPRAY made participants feel cooler and
      more comfortable and resulted in lower RPE (i.e., less exertion) yet performance
      was unchanged [TT completion: CONTROL-SPRAY 32.4 (2.9) and MENTHOL-SPRAY 32.7
      (3.0) min]. Trec rate of increase was 1.40 (0.60) and 1.45 (0.40)  degrees C/h
      after CONTROL-SPRAY and MENTHOL-SPRAY application, which were not different.
      Spraying L-menthol toward the end of self-paced exercise in the heat improved
      perception, but did not alter performance and did not increase heat illness risk.

PMID- 25943674
TI  - Effectiveness of cold water immersion for treating exertional heat stress when
      immediate response is not possible.
AB  - Immediate treatment with cold water immersion (CWI) is the gold standard for
      exertional heatstroke. In the field, however, treatment is often delayed due to
      delayed paramedic response and/or inaccurate diagnosis. We examined the effect of
      treatment (reduction of rectal temperature to 37.5  degrees C) delays of 5, 20,
      and 40 min on core cooling rates in eight exertionally heat-stressed (40.0 
      degrees C rectal temperature) individuals. We found that rectal temperature was
      elevated above baseline (P < 0.05) at the end of all delay periods (5 min: 40.08
      +/- 0.32; 20 min: 39.92 +/- 0.40; 40 min: 39.57 +/- 0.29  degrees C). Mean
      arterial pressure was reduced (P < 0.05) below baseline (92 +/- 1.8 mm Hg) after
      all delay periods (5 min: 75 +/- 2.6; 20 min: 74 +/- 1.7; 40 min: 70 +/- 2.1 mm
      Hg; P > 0.05). Rectal core cooling rates were similar among conditions (5 min:
      0.20 +/- 0.01; 20 min: 0.17 +/- 0.02; 40 min: 0.17 +/- 0.01  degrees C/min; P >
      0.05). The rectal temperature afterdrop following CWI was similar across
      conditions (5 min: 35.95; 20 min: 35.61; 40 min: 35.87  degrees C; P > 0.05). We
      conclude that the effectiveness of 2  degrees C CWI as a treatment for exertional
      heat stress remains high even when applied with a delay of 40 min. Therefore, our
      results support that CWI is the most appropriate treatment for exertional
      heatstroke as it is capable of quickly reversing hyperthermia even when treatment
      is commenced with a significant delay. 

PMID- 25943675
TI  - Time course of natural heat acclimatization in well-trained cyclists during a 2
      week training camp in the heat.
AB  - The aim of this study was to determine the time course of physiological
      adaptations and their relationship with performance improvements during 2 weeks
      of heat acclimatization. Nine trained cyclists completed 2 weeks of training in
      naturally hot environment (34 +/- 3  degrees C; 18 +/- 5% relative humidity). On
      days 1, 6, and 13, they performed standardized heat response tests (HRT-1, 2, 3),
      and 43.4-km time trials in the heat (TTH-1, 2, 3) were completed on days 2, 7,
      and 14. Within the first 5-6 days, sweat sodium concentration decreased from 75
      +/- 22 mmol/L to 52 +/- 24 mmol/L, sweat rate increased (+20 +/- 15%), and
      resting hematocrit decreased (-5.6 +/- 5.4%), with no further changes during the
      remaining period. In contrast, power output during TTHs gradually improved from
      TTH-1 to TTH-2 (+11 +/- 8%), and from TTH-2 to TTH-3 (+5 +/- 4%). Individual
      improvements in performance from TTH-1 to TTH-2 correlated with individual
      changes in hematocrit (assessed after the corresponding HRT; r = -0.79, P <
      0.05), however, were not related to changes in performance from TTH-2 to TTH-3.
      In trained athletes, sudomotor and hematological adaptations occurred within 5-6
      days of training, whereas the additional improvement in performance after the
      entire acclimatization period did not relate to changes in these parameters. 

PMID- 25943676
TI  - A comparison of males and females' temporal patterning to short- and long-term
      heat acclimation.
AB  - The current study assessed sex differences in thermoregulatory and physiological
      adaptation to short-term (STHA) and long-term heat acclimation (LTHA). Sixteen
      (eight males; eight females) participants performed three running heat tolerance
      tests (RHTT), preceding HA (RHTT1), following 5 days HA (RHTT2) and 10 days HA
      (RHTT3). The RHTT involved 30-min running (9 km/h, 2% gradient) in 40  degrees C,
      40% relative humidity. Following STHA, resting rectal temperature (Trrest )
      (males: -0.24 +/- 0.16  degrees C, P <= 0.001; females: -0.02 +/- 0.08  degrees
      C, P = 0.597), peak rectal temperature (Trpeak ) (males: -0.39 +/- 0.36  degrees
      C, P <= 0.001; females -0.07 +/- 0.18  degrees C, P = 0.504), and peak heart rate
      (males: -14 +/- 12 beats/min, P <= 0.001; females: -5 +/- 3 beats/min, P = 0.164)
      reduced in males, but not females. Following STHA, sweat rate relative to body
      surface area (SRBSA ) increased (428 +/- 269 g/h/m(2) , P = 0.029) in females,
      but not males (-11 +/- 286 g/h/m(2) , P = 0.029). Following LTHA, Trrest (males: 
      0.04 +/- 0.15  degrees C, P = 0.459; females: -0.22 +/- 0.12  degrees C, P <=
      0.01) and Trpeak (males: -0.05 +/- 0.26  degrees C, P = 0.590; females: -0.41 +/-
      0.24  degrees C, P <= 0.01) reduced in females, but not males. Following LTHA,
      SRBSA increased in males (308 +/- 346 g/h/m(2) , P = 0.029), but not females (44
      +/- 373 g/h/m(2) , P = 0.733). Males and females responded to STHA; however,
      females required LTHA to establish thermoregulatory and cardiovascular stability.
      HA protocols should be designed to target sex differences in thermoregulation for
      optimal adaptation. 

PMID- 25943677
TI  - Isothermic and fixed-intensity heat acclimation methods elicit equal increases in
      Hsp72 mRNA.
AB  - Thermotolerance, to which heat shock protein-72 (Hsp72) contributes, is an
      acquired state achieved following heat acclimation (HA), eliciting cellular
      adaption and protection against thermal stress. Optimal HA methods achieving the
      greatest heat shock response (HSR) are equivocal; therefore, investigation of
      methods provoking the greatest sustained HSR is required to optimize cellular
      adaptation. Twenty-four males performed short-term HA (STHA; five sessions) and
      long-term HA (LTHA; STHA plus further five sessions) utilizing fixed-intensity
      (FIXED; workload = 50% V  O 2 p e a k ), continuous isothermic HA [ISOCONT ;
      target rectal temperature (Trec ) = 38.5  degrees C], or progressive isothermic
      HA (ISOPROG ; target Trec  = 38.5  degrees C for STHA then target Trec  = 39.0 
      degrees C for LTHA). Leukocyte Hsp72 mRNA was measured pre- and post day 1, day
      5, and day 10 of HA via reverse transcription quantitative polymerase chain
      reaction to determine the HSR. Hsp72 mRNA increased (P < 0.05) pre- to post day
      1, pre- to post day 5, and pre to post day 10 in FIXED, ISOCONT , and ISOPROG ,
      but no differences were observed between methods (P > 0.05). The equal Hsp72 mRNA
      increases occurring from consistent, reduced, or increased endogenous strain
      following STHA and LTHA suggest that transcription occurs following attainment of
      sufficient endogenous criteria. These data give confidence that all reported HA
      methods increase Hsp72 mRNA and are capable of eliciting adaptations toward
      thermotolerance. 

PMID- 25943678
TI  - Heat acclimatization does not improve VO2max or cycling performance in a cool
      climate in trained cyclists.
AB  - This study investigated if well-trained cyclists improve V  O 2 m a x and
      performance in cool conditions following heat acclimatization through natural
      outdoor training in hot conditions. Eighteen trained male cyclists were tested
      for physiological adaptations, V  O 2 m a x , peak aerobic power output, exercise
      efficiency, and outdoor time trial (TT) performance (43.4 km in cool environment,
      ~5-13  degrees C) before and after 2 weeks of training in a cool (CON, n = 9) or
      hot (~35  degrees C, HA, n = 9) environment. After heat acclimatization, TT
      performance in the heat was improved by 16%; however, there was no change in the
      HA group in V  O 2 m a x (4.79 +/- 0.21 L/min vs 4.82 +/- 0.35 L/min), peak
      aerobic power output (417 +/- 16 W vs 422 +/- 17 W), and outdoor TT performance
      in cool conditions (300 +/- 14 W/69 +/- 3 min vs 302 +/- 9 W/69 +/- 4 min). The
      present study shows that 2 weeks of heat acclimatization was associated with
      marked improvements in TT performance in the heat. However, for the well-trained
      endurance athletes, this did not transfer to an improved aerobic exercise
      capacity or outdoor TT performance in cool conditions. 

PMID- 25943679
TI  - Swimming in warm water is ineffective in heat acclimation and is non-ergogenic
      for swimmers.
AB  - Heat acclimation (HA) in air confers adaptations that improve exercise
      capabilities in hot and possibly temperate air. Swimmers may benefit from HA, yet
      immersion may constrain adaptation. Therefore, we examined whether warm-water
      swimming constitutes effective HA. In a randomized-crossover study, eight male
      swimmers swam 60 min/day on 7 days in 33  degrees C (HA) or 28  degrees C (CON)
      water. They performed 20-min distance trials before and after each regime: in 33 
      degrees C water (Warm); 28  degrees C water (Temperate); and cycling in 29 
      degrees C air (Terrestrial) following standardized exercise. Rectal temperature
      (Tre ) rose ~ 1  degrees C in HA sessions, and sweat loss averaged 1.4 L/h. After
      accounting for CON, HA did not confer any clear expansion of plasma volume [1.9%
      (95% CI: 7.7)], reduction in heart rate during standardized cycling exercise [1
      b/min (9)], reduction in Tre during rest [+0.1  degrees C (0.1)] or exercise, or
      change in sudomotor function. Only perceived temperature and discomfort tended to
      improve. Performance was clearly not improved for Warm [+0.3% (1.8)] or Temperate
      [+0.3% (1.9)], was unclear for Terrestrial [+0.4% (17.7)], and was unrelated to
      changes in resting plasma volume (r < 0.3). In conclusion, short-term HA using
      swimming in 33  degrees C water confers little adaptation and is not ergogenic
      for warm or temperate conditions. 

PMID- 25943680
TI  - Monitoring training to assess changes in fitness and fatigue: The effects of
      training in heat and hypoxia.
AB  - This study examined the association between monitoring tools, training loads, and
      performance in concurrent heat and hypoxia (H + H) compared with temperate
      training environments. A randomized parallel matched-group design involved 18
      well-trained male cyclists. Participants performed 12 interval sessions (3 weeks)
      in either H + H (32 +/- 1  degrees C, 50% RH, 16.6% O2 normobaric hypoxia) or
      control (21  degrees C, 50% RH, 21% O2 ), followed by a seven-session taper (3
      weeks; 21  degrees C, 50% RH, 21% O2 ), while also maintaining external training
      (~ 6-10 h/week). A 20-km time trial (TT) was completed pre- and post-training
      block (21  degrees C, 50% RH, 21% O2 ). Before each TT and once weekly, a 4-min
      cycle warm-up (70% 4-min mean maximum power) was completed. Visual analog scale
      rating for pain, recovery, and fatigue was recorded before the warm-up, with
      heart rate (HREx ), heart rate recovery (HRR), and rating of perceived exertion
      (RPEWU ) recorded following. Training load was quantified using the session
      rating of perceived exertion (sRPE) method throughout. Overall TT improved 35 +/-
      47 s with moderate correlations to HRR (r = 0.49) and recovery (r = -0.55). H + H
      group had a likely greater reduction in HREx [ES = -0.50 (90% CL) (-0.88; 0.12)]
      throughout and a greater sRPE (ES = 1.20 [0.41; 1.99]), and reduction in HRR [ES
      = -0.37 (-0.70;-0.04)] through the overload. RPEWU was associated with weekly
      training load (r = 0.37). These findings suggest that recovery and HRR in a
      temperate environment may be used as simple measures to identify an athlete's
      readiness to perform. Alternatively, the relationship of RPEWU and training load
      suggests that perception of effort following a standardized warm-up may be a
      valid measure when monitoring an athlete's training response, irrespective of the
      training environment. 

PMID- 25943681
TI  - A reliable preloaded cycling time trial for use in conditions of significant
      thermal stress.
AB  - The purpose of this study was to assess the reliability of a 15-min time trial
      preloaded with 45 min of fixed-intensity cycling under laboratory conditions of
      thermal stress. Eight trained cyclists/triathletes (41 +/- 10 years, VO2 peak: 69
      +/- 8 mL/kg/min, peak aerobic power: 391 +/- 72 W) completed three trials (the
      first a familiarization) where they cycled at ~ 55% VO2 peak for 45 min followed
      by a 15-min time trial (~75% VO2 peak) under conditions of significant thermal
      stress (WBGT: 26.7 +/- 0.8  degrees C, frontal convective airflow: 20 km/h).
      Seven days separated the trials, which were conducted at the same time of day
      following 24 h of exercise and dietary control. Reliability increased when a
      familiarization trial was performed, with the resulting coefficient of variation
      and intraclass correlation coefficient of the work completed during the 15-min
      time trial, 3.6% and 0.96, respectively. Therefore, these results demonstrate a
      high level of reliability for a 15-min cycling time trial following a 45-min
      preload when performed under laboratory conditions of significant thermal stress
      using trained cyclists/triathletes. 

PMID- 25943682
TI  - Supernumerary punctum: an unusual case of seeing double.
AB  - Supernumerary punctum is an under-reported congenital anomaly, in which there is
      more than one lacrimal punctum. Although usually asymptomatic, supernumerary
      puncta have been reported to cause dry eye or epiphora (excessive tearing) and
      should be included in their differential diagnosis. Tearing is often associated
      with dry eyes and can lead to discontinuation of contact lens wear. A
      comprehensive evaluation of the causes of tearing may uncover other contributory
      factors of epiphora. This case report highlights unilateral inferior double
      puncta in an otherwise asymptomatic patient. Due to increased evacuation of tears
      in the affected eye, manual occlusion of the puncta was advocated to allow
      topical medication to be more efficacious. 

PMID- 25943683
TI  - Factors associated with disability and impact of tension-type headache: findings
      of the Korean headache survey.
AB  - BACKGROUND: Although mostly mild in symptom severity, tension-type headache (TTH)
      can cause disability. However, factors associated with disability of TTH have
      been rarely reported. This study sought to assess the factors associated with TTH
      related disability and impact. METHODS: We analyzed data form the Korean Headache
      Survey, a nation-wide survey regarding headache in all Korean adults aged 19-69
      years. TTH-related disability was measured by surveying actual disability and
      Headache Impact Test-6 (HIT-6). Actual disability was defined as having one or
      more days of activity restriction or missed activity due to headache in the last
      3 months. The HIT-6 score >= 50 was regarded as significant headache impact
      associated with TTH. We assessed factors associated with TTH-related disability
      and impact using logistic regression analyses adjusting for sociodemographic
      variables and headache characteristics. RESULTS: Among 1507 individuals, the 1
      year prevalence rate of TTH was 30.7% (n = 463), of which 4.8% reported actual
      disability and 21.3% had headache impact, respectively. In univariate analyses,
      sociodemographic variables were not associated with actual disability and
      headache impact, respectively. There were relationships between several headache
      characteristics and actual disability/headache impact. After adjustment of
      potential confounders, moderate headache intensity was correlated with actual
      disability (odds ratio [OR]: 4.41, 95% confidence interval [CI]: 1.46-13.27),
      while an inverse association was observed between no aggravation by routine
      activity and actual disability (OR: 0.32, 95% CI: 0.12-0.88). Multivariate
      analyses showed that ORs for headache impact were increased in those with higher
      headache frequency (OR: 2.54, 95% CI: 1.47-4.39 for 1-14 days/month; OR: 23.83,
      95% CI: 5.46-104.03 for >= 15 days/month), longer headache time duration (OR:
      1.84, 95% CI: 1.04-3.25 for >= 1 and < 4 hours; OR: 2.44 95% CI: 1.17-5.11 for >=
      4 hours), and phonophobia (OR: 1.73, 95% CI: 1.02-2.95), whereas decreased in
      those with no aggravation by routine activity (OR: 0.32, 95% CI: 0.12-0.88).
      CONCLUSIONS: Several headache characteristics were associated with actual
      disability and headache impact among TTH individuals. Our findings suggest that
      there needs to be consideration careful of troublesome headache characteristics
      for TTH individuals suffering from disability and impact.

PMID- 25943684
TI  - A Health Economic Evaluation of Stroke Prevention in Atrial Fibrillation:
      Guideline Adherence Versus the Observed Treatment Strategy Prior to 2012 in
      Denmark.
AB  - BACKGROUND: In 2012 the European Society of Cardiology (ESC) published new
      guidelines on pharmacological stroke prophylaxis in non-valvular atrial
      fibrillation (AF). The health economics of adhering to these guidelines in
      clinical practice remains to be elucidated. OBJECTIVE: This paper offers a health
      economic evaluation of two stroke-prophylactic treatment strategies: complete
      national adherence to the ESC guidelines on stroke prophylaxis in AF versus
      stroke-prophylactic treatment prior to 2012 in Denmark. METHODS: A cost-utility
      analysis was performed to compare two treatment strategies. The first strategy
      reflected national guideline adherence with the use of non-vitamin K antagonist
      oral anticoagulants (i.e. dabigatran etexilate), warfarin, and no treatment. The
      second strategy reflected observed stroke prophylaxis prior to 2012 with the
      utilization of warfarin, acetylsalicylic acid, and no treatment. A Danish health
      sector perspective was adopted. A Markov model was designed and populated with
      information on input parameters from the literature and local cost data
      reflecting 2014 values. A modeled patient cohort was constructed with a risk
      profile intended to reflect that of the Danish patient population with AF. The
      applied outcome was quality-adjusted life-years (QALYs). RESULTS: The incremental
      cost-effectiveness ratio amounted to <euro>3557 per QALY for the guideline
      adherent treatment strategy (GTS) compared with the pre-2012 treatment strategy.
      This ratio is below a threshold of <euro>25,000 (L20,000) per QALY. Sensitivity
      analyses revealed that the result was largely robust to changes in input
      parameters. All analyses found the GTS to be cost effective. CONCLUSIONS:
      Guideline adherence is a cost-effective treatment strategy compared with the
      strategy employed prior to 2012 for pharmacological stroke prophylaxis in AF.

PMID- 25943685
TI  - Calculating the Baseline Incidence in Patients Without Risk Factors: A Strategy
      for Economic Evaluation.
AB  - Economic and epidemiological models need various inputs to estimate the
      occurrence of events in different subsets of the population, such as the
      incidence of events for patients with risk factors compared with those without.
      However, the baseline event incidence for patients without risk factors
      (incidence_no_risk) may not be reported in the literature, therefore the event
      incidence in the population (incidence_pop) is commonly used in its place as the
      baseline. However, this is problematic because incidence_pop is a weighted
      average of a heterogeneous population. We therefore developed a method for
      deriving the incidence for persons without risk factors (incidence_no_risk) by
      adjustment of incidence_pop. We calculated incidence_no_risk using the relative
      risk for events due to risk factors (RR_risk), incidence_pop, and the prevalence
      of the risk factor (pRF), which are typically available in the literature. Since
      the incidence for patient with risk factors (incidence_risk) can be expressed as
      incidence_risk = incidence_no_risk * RR_risk, we found that incidence_no_risk =
      incidence_pop/((RR_risk * pRF) + (1 - pRF)). We validated the equation by
      modeling the fracture incidence in high-risk patients in an osteoporosis
      transition-state model. With incidence_pop used as the baseline fracture
      incidence, the model overestimated hip fractures in the study population (10.72
      fractures/1000 patient-years). After adjustment of incidence_pop using
      incidence_no_risk as the baseline incidence, the model accurately predicted hip
      fractures (2.27/1000 patient-years). Therefore, incidence_no_risk can be
      calculated using this method based on the event incidence for the study
      population, the relative risk increase associated with the risk factor, and the
      prevalence of the risk factor. 

PMID- 25943686
TI  - The Effect of Obesity and Chronic Conditions on Medicare Spending, 1987-2011.
AB  - BACKGROUND: Slowing the growth in Medicare expenditure is a key policy goal.
      Rising chronic disease prevalence is responsible for much of this growth.
      OBJECTIVE: The first goal of this study is to estimate the percentage of Medicare
      spending growth that is attributable to increasing disease prevalence rates of
      diabetes, hyperlipidaemia, hypertension and heart disease. Second, we estimate
      how much of this prevalence-related spending growth is attributable to rising
      obesity rates. METHODS: We employ spending decomposition equations to estimate
      the percentage of Medicare spending growth that is attributable to rising chronic
      disease prevalence, and we use two-part models to estimate the portion of
      prevalence-related spending that is potentially due to obesity. RESULTS: For our
      four conditions of interest, growing disease prevalence accounted for between
      13.6 % (in heart disease) and 58.9 % (in hyperlipidaemia) of Medicare expenditure
      growth. Up to 17.0 % (in diabetes) of the expenditure growth due to prevalence
      increases may be attributable to obesity and therefore may be modifiable.
      CONCLUSIONS: Rising obesity rates contribute to chronic disease prevalence,
      which, in turn, can lead to higher Medicare expenditures. To slow the growth in
      spending, policy makers should consider targeting obesity, using approaches such
      as improving pharmacotherapy coverage and providing intensive care coordination
      services to Medicare enrollees.

PMID- 25943687
TI  - Understanding device-structure-induced variations in open-circuit voltage for
      organic photovoltaics.
AB  - We investigate the structural influences on the device performance, especially on
      open-circuit voltage (V(OC)) in squaraine (SQ)/fullerene (C60) bilayer cells.
      Simply changing the SQ thickness could lead to 40% variation in V(OC) from 0.62
      to 0.86 V. The ionization potential (IP) of SQ films and recombination at the
      anode surface as well as donor/acceptor (D/A) interface sensitively vary with
      film thicknesses, which account for the shifts in V(OC). The anode recombination
      can be effectively suppressed by preventing direct contact between C60 and the
      anode with a buffer layer, delivering an elevated V(OC). Through polarized
      infrared-multiple-angle incidence resolution spectroscopy measurement, the
      molecular structure of SQ films is found to gradually evolve from lying-down on
      indium-tin oxide substrates with noncentrosymmetric orientation at low
      thicknesses to random structure at high thicknesses. The different molecular
      orientation may yield different strengths of electronic coupling, which affects
      the charge-carrier recombination and thus V(OC). Moreover, the oriented SQ films
      would spontaneously compose aligned dipole moments at the D/A interface because
      of the strong dipolar effects in SQ molecules identified by density functional
      theory calculations, whereas no aligned interfacial dipole moment exists in the
      random structure. The resulting interfacial dipole moments would form an electric
      field at the D/A interface, leading to variations in the IP and thus impacting
      V(OC). Our findings demonstrate that V(OC) in organic photovoltaic cells is
      critically associated with the molecular orientation that affects the charge
      carrier recombination and interfacial dipole alignment, which should be seriously
      taken into consideration for the design of organic molecules and optimization of
      the cell efficiency.

PMID- 25943688
TI  - Stroke unit Nurse Managers' views of individual and organizational factors liable
      to influence evidence-based practice: A survey.
AB  - The uptake of evidence into practice may be impeded or facilitated by individual
      and organizational factors within the local context. This study investigated
      Nurse Managers of New South Wales, Australia, stroke units (n = 19) in their
      views on: leadership ability (measured by the Leadership Practices Inventory),
      organizational learning (measured by the Organizational Learning Survey),
      attitudes and beliefs towards evidence-based practice (EBP) and readiness for
      change. Overall Nurse Managers reported high-level leadership skills and a
      culture of learning. Nurse Managers' attitude towards EBP was positive, although
      nursing colleague's attitudes were perceived as less positive. Nurse Managers
      agreed that implementing evidence in practice places additional demands on staff;
      and almost half (n = 9, 47%) reported that resources were not available for
      evidence implementation. The findings indicate that key persons responsible for
      evidence implementation are not allocated sufficient time to coordinate and
      implement guidelines into practice. The findings suggest that barriers to
      evidence uptake, including insufficient resources and time constraints,
      identified by Nurse Managers in this study are not likely to be unique to stroke
      units. Furthermore, Nurse Managers may be unable to address these organizational
      barriers (i.e. lack of resources) and thus provide all the components necessary
      to implement EBP. 

PMID- 25943689
TI  - Detecting balancing selection in genomes: limits and prospects.
AB  - In spite of the long-term interest in the process of balancing selection, its
      frequency in genomes and evolutionary significance remain unclear due to
      challenges related to its detection. Current statistical approaches based on
      patterns of variation observed in molecular data suffer from low power and a high
      incidence of false positives. This raises the question whether balancing
      selection is rare or is simply difficult to detect. We discuss genetic signatures
      produced by this mode of selection and review the current approaches used for
      their identification in genomes. Advantages and disadvantages of the available
      methods are presented, and areas where improvement is possible are identified.
      Increased specificity and reduced rate of false positives may be achieved by
      using a demographic model, applying combinations of tests, appropriate sampling
      scheme and taking into account intralocus variation in selection pressures. We
      emphasize novel solutions, recently developed model-based approaches and good
      practices that should be implemented in future studies looking for signals of
      balancing selection. We also draw attention of the readers to the results of
      recent theoretical studies, which suggest that balancing selection may be
      ubiquitous but transient, leaving few signatures detectable by existing methods.
      Testing this new theory may require the development of novel high-throughput
      methods extending beyond genomic scans. 

PMID- 25943690
TI  - Boymaw, overexpressed in brains with major psychiatric disorders, may encode a
      small protein to inhibit mitochondrial function and protein translation.
AB  - The t(1,11) chromosome translocation co-segregates with major psychiatric
      disorders in a large Scottish family. The translocation disrupts the DISC1and
      Boymaw (DISC1FP1) genes on chromosomes 1 and 11, respectively. After
      translocation, two fusion genes are generated. Our recent studies found that the
      DISC1-Boymaw fusion protein is localized in mitochondria and inhibits
      oxidoreductase activity, rRNA expression, and protein translation. Mice carrying
      the DISC1-Boymaw fusion genes display intermediate behavioral phenotypes related
      to major psychiatric disorders. Here, we report that the Boymaw gene may encode a
      small protein predominantly localized in mitochondria. The Boymaw protein
      inhibits oxidoreductase activity, rRNA expression, and protein translation in the
      same way as the DISC1-Boymaw fusion protein. Interestingly, Boymaw expression is
      up-regulated by different stressors at RNA and/or protein translational levels.
      In addition, we found that Boymaw RNA expression is significantly increased in
      the postmortem brains of patients with major psychiatric disorders. Our studies
      therefore suggest that the Boymaw gene could potentially be a susceptibility gene
      for major psychiatric disorders in both the Scottish t(1,11) family and the
      general population of patients.

PMID- 25943691
TI  - Contribution of acoustic radiation force impulse (ARFI) elastography to the
      ultrasound diagnosis of biliary atresia.
AB  - BACKGROUND: Children with biliary atresia rapidly develop liver fibrosis
      secondary to inflammatory destruction of the biliary tract. Noninvasive detection
      of liver fibrosis in neonatal/infantile cholestasis is an additional criterion
      for the diagnosis of biliary atresia, leading to prompt surgical exploration.
      OBJECTIVE: To assess the value of US with acoustic radiation force impulse (ARFI)
      elastography to detect biliary atresia in the workup of neonatal/infantile
      cholestasis. MATERIALS AND METHODS: In this retrospective study, 20 children with
      cholestasis suspected of having biliary atresia were investigated by US and ARFI.
      We evaluated the association between US findings and the diagnosis of biliary
      atresia and with two scores of liver fibrosis obtained from liver biopsy.
      RESULTS: In univariate analyses, gallbladder size, triangular cord sign, spleen
      size and ARFI values were found to be associated with biliary atresia, though
      only the triangular cord sign remained significant when elevated gamma
      glutamyltransferase (GGT) was included as a predictor. In contrast, spleen size
      and ARFI correlated with the degree of liver fibrosis on biopsy (r > 0.70, P <
      0.001), which remained significant when gamma glutamyltransferase elevation was
      included as a predictor. CONCLUSION: The addition of ARFI to a standard abdominal
      US in the initial workup of the neonate with possible infantile cholestasis can
      provide reliable information on liver fibrosis and help in the diagnosis of
      biliary atresia.

PMID- 25943692
TI  - Olfactory receptor genes cooperate with protocadherin genes in human extreme
      obesity.
AB  - Worldwide, the incidence of obesity has increased dramatically over the past
      decades. More knowledge about the complex etiology of obesity is needed in order
      to find additional approaches for treatment and prevention. Investigating the
      exome sequencing data of 30 extremely obese subjects (BMI 45-65 kg/m(2)) shows
      that predicted damaging missense variants in olfactory receptor genes on
      chromosome 1q and rare predicted damaging variants in the protocadherin (PCDH)
      beta-cluster genes on chromosome 5q31, reported in our previous work, co-localize
      in subjects with extreme obesity. This implies a synergistic effect between
      genetic variation in these gene clusters in the predisposition to extreme
      obesity. Evidence for a general involvement of the olfactory transduction pathway
      on itself could not be found. Bioinformatic analysis indicates a specific
      involvement of the PCDH beta-cluster genes in controlling tissue development.
      Further mechanistic insight needs to await the identification of the ligands of
      the 1q olfactory receptors. Eventually, this may provide the possibility to
      manipulate food flavor in a way to reduce the risk of overeating and of extreme
      obesity in genetically predisposed subjects. 

PMID- 25943694
TI  - Nasal bone fractures are successfully managed under local anaesthesia -
      experience on 483 patients.

PMID- 25943693
TI  - [Multiphoton tomography].
AB  - In recent years, multiphoton tomography (MPT) and multiphoton microscopy have
      gained increasing importance as noninvasive examination techniques in
      dermatology. MPT imaging is based on the specific stimulation of biogenic
      fluorophores. The induction of second harmonic generation is also used for
      imaging of particular molecules. Additional fluorescence staining or fluorescence
      markers are not necessary-an important advantage for the in vivo examination of
      human skin. Multiphoton techniques are not only appropriate for clinical
      diagnostics but also for biomedical research. MPT provides an optical biopsy
      depth up to 200 um with subcellular resolution depicting cellular and
      extracellular structures. In combination with fluorescence lifetime imaging,
      additional information about the microenvironment, the energetic state and the
      cellular metabolism can be obtained. This review presents recent developments of
      MPT for the in vivo evaluation of physiological and pathological changes of skin
      and diagnostics of dermal diseases. 

PMID- 25943695
TI  - Prdx4 is a compartment-specific H2O2 sensor that regulates neurogenesis by
      controlling surface expression of GDE2.
AB  - Neural progenitors and terminally differentiated neurons show distinct redox
      profiles, suggesting that coupled-redox cascades regulate the initiation and
      progression of neuronal differentiation. Discrete cellular compartments have
      different redox environments and how they contribute to differentiation is
      unclear. Here we show that Prdx4, an endoplasmic reticulum (ER) enzyme that
      metabolizes H2O2, acts as a tunable regulator of neurogenesis via its
      compartmentalized thiol-oxidative function. Prdx4 ablation causes premature motor
      neuron differentiation and progenitor depletion, leading to imbalances in subtype
      specific motor neurons. GDE2, a six-transmembrane protein that induces
      differentiation by downregulating Notch signalling through surface cleavage of
      GPI-anchored proteins, is targeted by Prdx4 oxidative activity. Prdx4 dimers
      generated by H2O2 metabolism oxidize two cysteine residues within the GDE2
      enzymatic domain, which blocks GDE2 trafficking to the plasma membrane and
      prevents GDE2 neurogeneic function. Thus, Prdx4 oxidative activity acts as a
      sensor to directly couple neuronal differentiation with redox environments in the
      ER. 

PMID- 25943696
TI  - Laparoscopic repair of an incarcerated Bochdalek hernia in an elderly man.

PMID- 25943697
TI  - An unusual presentation of acute appendicitis with mobile cecum syndrome.

PMID- 25943698
TI  - Cohort study of physical activity and injury among Latino farm workers.
AB  - INTRODUCTION: This study characterized physical activity and its association with
      injury among Latino farm workers. METHODS: An interviewer-administered
      questionnaire was used to collect baseline and follow-up data on 843 and 640
      Latino farm workers, respectively. Participants were 18-55 years old, engaged in
      farm work and residing in Mendota, CA at baseline interview. The questionnaire
      assessed self-reported physical activity and risk of injury. RESULTS: The 12
      month prevalence of injury decreased from 9.0% at baseline to 6.9% at follow up
      interview. In GEE models adjusted for age, follow-up time, gender, smoking,
      income and years working in agriculture, poor/fair self-assessed health status
      (OR = 1.82, 95% CI: 1.18-2.82) and 2-3 hr per day of sitting/watching TV/using a
      computer (OR = 0.50, 95% CI: 0.30-0.83) were significantly associated with
      injury. CONCLUSIONS: Physical activity was not associated with injury in this
      population. Efforts to reduce injuries should focus on known risk factors such as
      poor health status.

PMID- 25943699
TI  - Age-related variations of protein carbonyls in human saliva and plasma: is saliva
      protein carbonyls an alternative biomarker of aging?
AB  - Free radical hypothesis which is one of the most acknowledged aging theories was
      developed into oxidative stress hypothesis. Protein carbonylation is by far one
      of the most widely used markers of protein oxidation. We studied the role of age
      and gender in protein carbonyl content of saliva and plasma among 273 Chinese
      healthy subjects (137 females and 136 males aged between 20 and 79) and discussed
      the correlation between protein carbonyl content of saliva and plasma. Protein
      carbonyl content of saliva and plasma were, respectively, 2.391 +/- 0.639 and
      0.838 +/- 0.274 nmol/mg. Variations of saliva and plasma different age groups all
      reached significant differences in both male and female (all p < 0.05) while both
      saliva and plasma protein carbonyls were found to be significantly correlated
      with age (r = 0.6582 and r = 0.5176, all p < 0.001). Gender was discovered to be
      unrelated to saliva and plasma protein carbonyl levels (all p > 0.05). Saliva and
      plasma protein carbonyls were positively related (r = 0.4405, p < 0.001).
      Surprisingly, saliva and plasma protein carbonyls/ferric reducing ability of
      plasma (FRAP) ratios were proved to be significantly correlated with age (r =
      0.7796 and r = 0.6938, all p < 0.001) while saliva protein carbonyls/FRAP ratio
      and plasma protein carbonyls/FRAP ratio were also correlated (r = 0.5573, p <
      0.001). We concluded that saliva protein carbonyls seem to be an alternative
      biomarker of aging while the mechanisms of protein carbonylation and oxidative
      stress and the relationship between saliva protein carbonyls and diseases need to
      be further investigated.

PMID- 25943700
TI  - Older men are more fatigable than young when matched for maximal power and knee
      extension angular velocity is unconstrained.
AB  - The underlying factors related to the divergent findings of age-related fatigue
      for dynamic tasks are not well understood. The purpose here was to investigate
      age-related fatigability and recovery between a repeated constrained (isokinetic)
      and an unconstrained velocity (isotonic) task, in which participants performed
      fatiguing contractions at the velocity (isokinetic) or resistance (isotonic)
      corresponding with maximal power. To compare between tasks, isotonic torque-power
      relationships were constructed prior to and following both fatiguing tasks and
      during short-term recovery. Contractile properties were recorded from 9 old (~75
      years) and 11 young (~25 years) men during three testing sessions. In the first
      session, maximal power was assessed, and sessions 2 and 3 involved an isokinetic
      or an isotonic concentric fatigue task performed until maximal power was reduced
      by 40 %. Compared with young, the older men performed the same number of
      contractions to task failure for the isokinetic task (~45 contractions), but 20 %
      fewer for the isotonic task (p < 0.05). Regardless of age and task, maximal
      voluntary isometric contraction strength, angular velocity, and power were
      reduced by ~30, ~13, and ~25 %, respectively, immediately following task failure,
      and only isometric torque was not recovered fully by 10 min. In conclusion, older
      men are more fatigable than the young when performing a repetitive maximal
      dynamic task at a relative resistance (isotonic) but not an absolute velocity
      (isokinetic), corresponding to maximal power.

PMID- 25943701
TI  - Characterization and mitigation of nitrous oxide (N2 O) emissions from partial
      and full-nitrification BNR processes based on post-anoxic aeration control.
AB  - It has been reported that a directional change from anoxic to aerobic conditions
      is a common trigger for nitrous oxide (N2 O) production by ammonia oxidizing
      bacteria (AOB). By extension, during anoxic-aerobic cycling, post-anoxic
      dissolved oxygen (DO) concentrations might likely play a role in the magnitude of
      N2 O emissions observed. The overall goal of this study was to determine the
      impact of three select post-anoxic DO concentrations (0.8, 2.0, and 3.0 mg O2 /L)
      on N2 O emissions from partial-nitrification (PN) and full-nitrification (FN)
      reactors subjected to anoxic-aerobic cycling and, ultimately, to explore the
      development of strategies to minimize N2 O emissions from PN and FN based
      biological nitrogen removal (BNR) processes. Statistically similar N2 O emissions
      were observed during anoxia for both PN (0.62 +/- 0.21% N load) and FN (0.61 +/-
      0.070% N load) processes. In contrast, N2 O emissions were statistically lower
      for PN (0.86 +/- 0.25% N load) than for FN (4.6 +/- 2.8% N load), during the post
      anoxic aerobic phase, when compared together for all three post-anoxic DO
      concentrations. Further, for PN, the highest N2 O emissions were observed at the
      highest post-anoxic DO concentration of 3.0 mg O2 /L (1.2% N load), likely due to
      the highest corresponding AOB specific growth rate. In contrast, for FN, the
      highest N2 O emissions were at the lowest post-anoxic DO concentration of 0.8 mg
      O2 /L (8.5% N load). The higher emissions from FN process at low DO
      concentrations were associated with a lag in nitrite oxidizing bacteria activity
      upon recovery to aerobic conditions. This lag phase contributed to transient
      nitrite accumulation, and in turn correlated positively to the observed N2 O
      emissions. Based on our findings, a gradual ramp up in post-anoxic DO
      concentrations can minimize N2 O emissions during PN-based BNR, whereas a
      completely different strategy, entailing a rapid increase in post-anoxic DO
      concentrations can minimize emissions during FN-based BNR operations.

PMID- 25943702
TI  - Modulation of neuronal activity by reward identity in the monkey subthalamic
      nucleus.
AB  - The subthalamic nucleus (STN) has been argued to be an important component of
      reward-sensitive basal ganglia circuitry. This view is especially supported by
      the behavioral changes observed after STN inactivation, which could reflect
      impairments in the motivational control of action. However, it is still unclear
      how the STN integrates reward information and to what extent such integration
      correlates with behavior. In this study, the response properties of STN neurons
      in monkeys performing reaching movements with a cue predicting the identity of an
      upcoming liquid reward (juice or water) were investigated. Although the timing of
      movements reliably indicated that monkeys had greater motivation for juice than
      water, rarely did task-related changes in neuronal activity depend on the nature
      of the expected reward. Conversely, when presented with a choice of selecting a
      response that leads to juice or water delivery, animals showed a clear preference
      for juice and more than half of the neurons were differentially modulated
      dependent on the reward obtained, mostly after the monkeys's overt choice of
      action. Under such circumstances, an increase in activity specifically followed
      the action outcomes across the population of neurons when monkeys failed to
      choose the juice reward. These results indicate that STN neurons encode whether
      or not a preferred reward had been received when a choice between response
      alternatives is required. This differential neuronal activity might reflect the
      participation of the STN in evaluating the reward value of chosen actions, thus
      highlighting its contribution to decision-making processes. 

PMID- 25943703
TI  - Robotic oncologic complexity score - a new tool for predicting complications in
      computer-enhanced oncologic surgery.
AB  - BACKGROUND: While there is little doubt that robotic interventions have already
      opened new horizons in surgery due to its inherent complexity, there is still an
      unmet need for tools allowing center-to-center performance comparisons. A
      complexity score could be a valuable instrument for further research. METHODS:
      The items of the robotic oncologic complexity score (ROCS) were based on risk
      factors identified in previous studies. We attempt to build the score and
      validate it on 400 consecutive cases of robotic oncologic surgery. The primary
      endpoint is to assess the value of ROCS in predicting major complications.
      RESULTS: The mean ROCS in the group was 3.3(+/-1.4). Different correlations were
      calculated: the score and the complications (r=0.38), the major complications
      (r=0.42), Clavien grade (r=0.5), the operating time (r=0.35), and the length of
      stay (r=0.47). On the ROC-curve a score >4 has the best specificity and
      sensibility for predicting major complications (P<0.05). CONCLUSION: ROCS has
      potential in predicting complications and hospital length of stay, as well as a
      role in classifying oncologic robotic surgical interventions. Copyright (c) 2015
      John Wiley & Sons, Ltd.

PMID- 25943704
TI  - Direct electrochemistry of glucose oxidase on novel free-standing nitrogen-doped
      carbon nanospheres@carbon nanofibers composite film.
AB  - We have proposed a novel free-standing nitrogen-doped carbon nanospheres@carbon
      nanofibers (NCNSs@CNFs) composite film with high processability for the
      investigation of the direct electron transfer (DET) of glucose oxidase (GOx) and
      the DET-based glucose biosensing. The composites were simply prepared by
      controlled thermal treatment of electrospun polypyrrole nanospheres doped
      polyacrylonitrile nanofibers (PPyNSs@PAN NFs). Without any pretreatment, the as
      prepared material can directly serve as a platform for GOx immobilization. The
      cyclic voltammetry of immobilized GOx showed a pair of well-defined redox peaks
      in O2-free solution, indicating the DET of GOx. With the addition of glucose, the
      anodic peak current increased, while the cathodic peak current decreased, which
      demonstrated the DET-based bioelectrocatalysis. The detection of glucose based on
      the DET of GOx was achieved, which displayed high sensitivity, stability and
      selectivity, with a low detection limit of 2 MUM and wide linear range of 12-1000
      MUM. These results demonstrate that the as-obtained NCNSs@CNFs can serve as an
      ideal platform for the construction of the third-generation glucose biosensor. 

PMID- 25943706
TI  - Cytokines, adhesion molecules, antiendothelial cell autoantibodies and vascular
      disease.
AB  - Vascular endothelial cells present a surface to circulating blood elements that
      is continuously changing its phenotype under the influence of cytokines and other
      soluble mediators, and as a result of cell-cell interactions. Phenotypic changes
      enable endothelial cells to respond to local environmental conditions, for
      example, promoting pro-inflammatory or pro-coagulant properties. Antibodies may
      also develop to structures on this changing endothelial surface. The
      characteristics of antiendothelial cell antibodies identified to date and their
      perceived role in vascular disease is discussed. 

PMID- 25943705
TI  - Analyses of soil microbial community compositions and functional genes reveal
      potential consequences of natural forest succession.
AB  - The succession of microbial community structure and function is a central
      ecological topic, as microbes drive the Earth's biogeochemical cycles. To
      elucidate the response and mechanistic underpinnings of soil microbial community
      structure and metabolic potential relevant to natural forest succession, we
      compared soil microbial communities from three adjacent natural forests: a
      coniferous forest (CF), a mixed broadleaf forest (MBF) and a deciduous broadleaf
      forest (DBF) on Shennongjia Mountain in central China. In contrary to plant
      communities, the microbial taxonomic diversity of the DBF was significantly (P <
      0.05) higher than those of CF and MBF, rendering their microbial community
      compositions markedly different. Consistently, microbial functional diversity was
      also highest in the DBF. Furthermore, a network analysis of microbial carbon and
      nitrogen cycling genes showed the network for the DBF samples was relatively
      large and tight, revealing strong couplings between microbes. Soil temperature,
      reflective of climate regimes, was important in shaping microbial communities at
      both taxonomic and functional gene levels. As a first glimpse of both the
      taxonomic and functional compositions of soil microbial communities, our results
      suggest that microbial community structure and function potentials will be
      altered by future environmental changes, which have implications for forest
      succession. 

PMID- 25943707
TI  - The discovery of circulation and the origin of modern medicine during the italian
      renaissance.
AB  - This historical article discusses the dawn of anatomy during the Italian
      Renaissance, the role of the University of Padua in the origin of modern
      medicine, milestones in the development of modern medicine, the discovery of
      circulation, Padua leadership and Galileo's persecution for his scientific
      theories. 

PMID- 25943709
TI  - Reply: To PMID 25735195.

PMID- 25943708
TI  - Interferon Gamma, but not Calcitriol Improves the Osteopetrotic Phenotypes in
      ADO2 Mice.
AB  - ADO2 is a heritable osteosclerotic disorder that usually results from
      heterozygous missense dominant negative mutations in the chloride channel 7 gene
      (CLCN7). ADO2 is characterized by a wide range of features and severity,
      including multiple fractures, impaired vision due to secondary bony overgrowth
      and/or the lack of the optical canal enlargement with growth, and
      osteonecrosis/osteomyelitis. The disease is presently incurable, although
      anecdotal evidence suggests that calcitriol and interferon gamma-1b (IFN-G) may
      have some beneficial effects. To identify the role of these drugs for the
      treatment of ADO2, we utilized a knock-in (G213R mutation in Clcn7) ADO2 mouse
      model that resembles the human disease. Six-week-old ADO2 heterozygous mice were
      administered vehicle (PBS) or calcitriol or IFN-G 5 times per week for 8 weeks.
      We determined bone phenotypes using DXA and MUCT, and analyzed serum biochemistry
      and bone resorption markers. ADO2 mice treated with all doses of IFN-G
      significantly (p<0.05) attenuated the increase of whole body aBMD and distal
      femur BV/TV gain in both male and female compared to the vehicle group. In
      contrast, mice treated with low and medium doses of calcitriol showed a trend of
      higher aBMD and BV/TV whereas high dose calcitriol significantly (p<0.05)
      increased bone mass compared to the vehicle group. The calcium and phosphorus
      levels did not differ between vehicle and IFN-G or calcitriol treated mice;
      however, we detected significantly (p<0.05) elevated levels of CTX/TRAP5b ratio
      in IFN-G treated mice. Our findings indicate that while IFN-G at all doses
      substantially improved the osteopetrotic phenotypes in ADO2 heterozygous mice,
      calcitriol treatment at any dose did not improve the phenotype and at high dose
      further increased bone mass. Thus, use of high dose calcitriol therapy in ADO2
      patients merits serious reconsideration. Importantly, our data support the
      prospect of a clinical trial of IFN-G in ADO2 patients. 

PMID- 25943710
TI  - Multiple amplification detection of microRNA based on the host-guest interaction
      between beta-cyclodextrin polymer and pyrene.
AB  - MicroRNAs (miRNAs) participate in various biological processes during the course
      of life. The levels of miRNAs can be useful biomarkers for cellular events or
      cancer diagnosis, thus sensitive and accurate analysis of miRNA expression is
      crucial for better understanding its functions and the early diagnosis of human
      disease. Here, we developed a multiple amplification detection method for miRNA
      based on the host-guest interaction between beta-cyclodextrin polymer and pyrene,
      which takes advantage of the polymerase-aided strand displacement amplification
      and lambda exonuclease-assisted cyclic enzymatic amplification. The proposed
      method allowed quantitative detection of miRNA-21 in a dynamic range of 1 pM to 5
      nM with a detection limit of 0.3 pM and demonstrated good ability to discriminate
      the target sequence from the single-base mismatched miRNA sequence. Moreover, the
      assay was applied successfully in a complex biological matrix. We believe that
      this proposed sensitive and specific assay has great potential as a
      quantification method for miRNA detection in biomedical research and clinical
      diagnosis. 

PMID- 25943711
TI  - The Effect of Phacoemulsification on Intraocular Pressure in Glaucoma Patients: A
      Report by the American Academy of Ophthalmology.
AB  - OBJECTIVE: To examine effects of phacoemulsification on longer-term intraocular
      pressure (IOP) in patients with medically treated primary open-angle glaucoma
      (POAG; including normal-tension glaucoma), pseudoexfoliation glaucoma (PXG), or
      primary angle-closure glaucoma (PACG), without prior or concurrent incisional
      glaucoma surgery. METHODS: PubMed and Cochrane database searches, last conducted
      in December 2014, yielded 541 unique citations. Panel members reviewed titles and
      abstracts and selected 86 for further review. The panel reviewed these articles
      and identified 32 studies meeting the inclusion criteria, for which the panel
      methodologist assigned a level of evidence based on standardized grading adopted
      by the American Academy of Ophthalmology. One, 15, and 16 studies were rated as
      providing level I, II, and III evidence, respectively. RESULTS: All follow-up,
      IOP, and medication data listed are weighted means. In general, the studies
      reported on patients using few glaucoma medications (1.5-1.9 before surgery among
      the different diagnoses). For POAG, 9 studies (total, 461 patients; follow-up, 17
      months) showed that phacoemulsification reduced IOP by 13% and glaucoma
      medications by 12%. For PXG, 5 studies (total, 132 patients; follow-up, 34
      months) showed phacoemulsification reduced IOP by 20% and glaucoma medications by
      35%. For chronic PACG, 12 studies (total, 495 patients; follow-up, 16 months)
      showed phacoemulsification reduced IOP by 30% and glaucoma medications by 58%.
      Patients with acute PACG (4 studies; total, 119 patients; follow-up, 24 months)
      had a 71% reduction from presenting IOP and rarely required long-term glaucoma
      medications when phacoemulsification was performed soon after medical reduction
      of IOP. Trabeculectomy after phacoemulsification was uncommon; the median rate
      reported within 6 to 24 months of follow-up in patients with controlled POAG,
      PXG, or PACG was 0% and was 7% in patients with uncontrolled chronic PACG.
      CONCLUSIONS: Phacoemulsification typically results in small, moderate, and marked
      reductions of IOP and medications for patients with POAG, PXG, and PACG,
      respectively, and using 1 to 2 medications before surgery. Trabeculectomy within
      6 to 24 months after phacoemulsification is rare in such patients. However,
      reports on its effects in eyes with advanced disease or poor IOP control before
      surgery are few, particularly for POAG and PXG.

PMID- 25943712
TI  - Morbidly obese patient with non-alcoholic steatohepatitis-related cirrhosis who
      died from sepsis caused by dental infection of Porphyromonas gingivalis: A case
      report.
AB  - Non-alcoholic steatohepatitis (NASH) is associated with increased risks of
      developing lifestyle-related diseases including type 2 diabetes, cardiovascular
      disease and cerebral vessel disease. While the two-hit hypothesis and, recently,
      multiple parallel hits hypothesis of NASH pathogenesis were proposed, further
      details have not emerged. Recently, dental infection of Porphyromonas gingivalis
      (P. gingivalis) has been reported as a critical risk factor for NASH progression,
      which acts as multiple parallel hits to induce inflammation and fibrogenic
      responses in steatosis. We describe here a 54-year-old woman who died from sepsis
      and was diagnosed with NASH. Briefly, her body mass index (BMI) at the age of 35
      years old had been 25.6 kg/m(2) , but she became obese after withdrawing into her
      home at the age of 45 years. Severe obesity continued over 19 years without
      diabetes mellitus. She was admitted to our hospital due to a sudden disturbance
      of consciousness. On admission, her BMI was 48.5 kg/m(2) . Computed tomography
      revealed cirrhotic liver with massive ascites, and laboratory data indicated
      increased inflammatory responses, renal failure and C grade Child-Pugh
      classification, suggesting the diagnosis of sepsis. Also, severe periodontal
      disease was present, because the patient's front teeth fell out easily during
      intubation. Although the focus of infection was not specified, the oral flora
      Parvimonas micra, a periodontal pathogen, was detected in venous blood. In spite
      of intensive care including artificial respiration management and continuous
      hemodiafiltration, she died on the 43rd day after admission. Surprisingly, P.
      gingivalis was detected in her hepatocytes. This case may represent the
      significance of P. gingivalis in the progress to cirrhosis in NASH patients. 

PMID- 25943713
TI  - Regulation of Hox orthologues in the oyster Crassostrea gigas evidences a
      functional role for promoter DNA methylation in an invertebrate.
AB  - DNA methylation within promoter regions (PRDM) controls vertebrate early gene
      transcription and thereby development, but is neglected outside this group.
      However, epigenetic features in the oyster Crassostrea gigas suggest functional
      significance of PDRM in invertebrates. To investigate this, reporter constructs
      containing in vitro methylated oyster Hox gene promoters were transfected into
      oyster embryos. The influence of in vivo methylation was studied using bisulfite
      sequencing and DNA methyltransferase inhibition during development. Our results
      demonstrate that methylation controls the transcriptional activity of the
      promoters investigated, unraveling a functional role for PRDM in a
      lophotrochozoan, an important finding regarding the evolution of epigenetic
      regulation. 

PMID- 25943714
TI  - Effects of acepromazine or dexmedetomidine on fentanyl disposition in dogs during
      recovery from isoflurane anesthesia.
AB  - OBJECTIVE: To describe fentanyl pharmacokinetics during isoflurane anesthesia and
      on recovery from anesthesia with concurrent administration of acepromazine,
      dexmedetomidine or saline in dogs. STUDY DESIGN: Experimental blinded,
      randomized, crossover study. ANIMALS: Seven adult hound dogs. METHODS: Dogs were
      administered intravenous (IV) fentanyl as a bolus (5 MUg kg(-1)) followed by an
      infusion (5 MUg kg(-1) hour(-1)) for 120 minutes during isoflurane anesthesia and
      emergence from anesthesia, and for 60 minutes after extubation during recovery
      from anesthesia. At the time of extubation, dexmedetomidine (2.5 MUg kg(-1)),
      acepromazine (0.05 mg kg(-1)) or saline were administered IV. Venous blood was
      sampled during the maintenance and recovery periods. Fentanyl plasma
      concentrations were measured using high-performance liquid chromatography-mass
      spectrometry and population pharmacokinetic analyses were performed. RESULTS:
      Mean fentanyl plasma concentrations were 1.6-4.5 ng mL(-1) during isoflurane
      anesthesia and 1.6-2.0 ng mL(-1) during recovery from anesthesia. Recovery from
      isoflurane anesthesia without sedation was associated with an increase in the
      volume of the central compartment from 0.80 to 1.02 L kg(-1). After
      administration of acepromazine, systemic clearance of fentanyl increased from
      31.5 to 40.3 mL minute(-1) kg(-1) and the volume of the central compartment
      increased from 0.70 to 0.94 L kg(-1). Administration of dexmedetomidine did not
      significantly change fentanyl pharmacokinetics. Inter-individual variability for
      fentanyl parameter estimates in all treatments ranged from 2.2% to 54.5%, and
      residual error ranged from 6.3% to 13.4%. CONCLUSIONS AND CLINICAL RELEVANCE: The
      dose rates of fentanyl used in this study achieved previously established
      analgesic plasma concentrations for the duration of the infusion. Despite
      alterations in fentanyl pharmacokinetics, differences in fentanyl plasma
      concentrations among treatments during recovery from anesthesia were small and
      were unlikely to be of clinical significance.

PMID- 25943715
TI  - Longer-term outcomes of darbepoetin alfa versus epoetin alfa in patients with
      ESRD initiating hemodialysis: a quasi-experimental cohort study.
AB  - BACKGROUND: Adequately powered studies directly comparing hard clinical outcomes
      of darbepoetin alfa (DPO) versus epoetin alfa (EPO) in patients undergoing
      dialysis are lacking. STUDY DESIGN: Observational, registry-based, retrospective
      cohort study; we mimicked a cluster-randomized trial by comparing mortality and
      cardiovascular events in US patients initiating hemodialysis therapy in
      facilities (almost) exclusively using DPO versus EPO. SETTING & PARTICIPANTS:
      Nonchain US hemodialysis facilities; each facility switching from EPO to DPO
      (2003-2010) was matched for location, profit status, and facility type with one
      EPO facility. Patients subsequently initiating hemodialysis therapy in these
      facilities were assigned their facility-level exposure. INTERVENTION: DPO versus
      EPO. OUTCOMES: All-cause mortality, cardiovascular mortality; composite of
      cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal stroke.
      MEASUREMENTS: Unadjusted and adjusted HRs from Cox proportional hazards
      regression models. RESULTS: Of 508 dialysis facilities that switched to DPO, 492
      were matched with a similar EPO facility; 19,932 (DPO: 9,465 [47.5%]; EPO: 10,467
      [52.5%]) incident hemodialysis patients were followed up for 21,918 person-years
      during which 5,550 deaths occurred. Almost all baseline characteristics were
      tightly balanced. The demographics-adjusted mortality HR for DPO (vs EPO) was
      1.06 (95% CI, 1.00-1.13) and was materially unchanged after adjustment for all
      other baseline characteristics (HR, 1.05; 95% CI, 0.99-1.12). Cardiovascular
      mortality did not differ between groups (HR, 1.05; 95% CI, 0.94-1.16). Nonfatal
      outcomes were evaluated among 9,455 patients with fee-for-service Medicare: 4,542
      (48.0%) in DPO and 4,913 (52.0%) in EPO facilities. During 10,457 and 10,363
      person-years, 248 and 372 events were recorded, respectively, for strokes and
      MIs. We found no differences in adjusted stroke or MI rates or their composite
      with cardiovascular death (HR, 1.10; 95% CI, 0.96-1.25). LIMITATIONS: Nonrandom
      treatment assignment, potential residual confounding. CONCLUSIONS: In incident
      hemodialysis patients, mortality and cardiovascular event rates did not differ
      between patients treated at facilities predominantly using DPO versus EPO.

PMID- 25943716
TI  - Research Priorities in CKD: Report of a National Workshop Conducted in Australia.
AB  - Research aims to improve health outcomes for patients. However, the setting of
      research priorities is usually performed by clinicians, academics, and funders,
      with little involvement of patients or caregivers and using processes that lack
      transparency. A national workshop was convened in Australia to generate and
      prioritize research questions in chronic kidney disease (CKD) among diverse
      stakeholder groups. Patients with CKD (n=23), nephrologists/surgeons (n=16),
      nurses (n=8), caregivers (n=7), and allied health professionals and researchers
      (n=4) generated and voted on intervention questions across 4 treatment
      categories: CKD stages 1 to 5 (non-dialysis dependent), peritoneal dialysis,
      hemodialysis, and kidney transplantation. The 5 highest ranking questions (in
      descending order) were as follows: How effective are lifestyle programs for
      preventing deteriorating kidney function in early CKD? What strategies will
      improve family consent for deceased donor kidney donation, taking different
      cultural groups into account? What interventions can improve long-term post
      transplant outcomes? What are effective interventions for post hemodialysis
      fatigue? How can we improve and individualize drug therapy to control post
      transplant side effects? Priority questions were focused on prevention,
      lifestyle, quality of life, and long-term impact. These prioritized research
      questions can inform funding agencies, patient/consumer organizations, policy
      makers, and researchers in developing a CKD research agenda that is relevant to
      key stakeholders. 

PMID- 25943718
TI  - Thrombotic microangiopathy, cancer, and cancer drugs.
AB  - Thrombotic microangiopathy (TMA) is a complication that can develop directly from
      certain malignancies, but more often results from anticancer therapy. Currently,
      the incidence of cancer drug-induced TMA during the last few decades is >15%,
      primarily due to the introduction of anti-vascular endothelial growth factor
      (VEGF) agents. It is important for clinicians to understand the potential causes
      of cancer drug-induced TMA to facilitate successful diagnosis and treatment. In
      general, cancer drug-induced TMA can be classified into 2 types. Type I cancer
      drug-induced TMA includes chemotherapy regimens (ie, mitomycin C) that can
      potentially promote long-term kidney injury, as well as increased morbidity and
      mortality. Type II cancer drug-induced TMA includes anti-VEGF agents that are not
      typically associated with cumulative dose-dependent cell damage. In addition,
      functional recovery of kidney function often occurs after drug interruption,
      assuming a type I agent was not given prior to or during therapy. There are no
      randomized controlled trials to provide physician guidance in the management of
      TMA. However, previously accumulated information and research suggest that
      endothelial cell damage has an underlying immunologic basis. Based on this, the
      emerging trend includes the use of immunosuppressive agents if a refractory or
      relapsing clinical course that does not respond to plasmapheresis and steroids is
      observed. 

PMID- 25943719
TI  - The urine sediment as a biomarker of kidney disease.
AB  - The modern era of medicine has ushered in new diagnostic technologies to assist
      the clinician in evaluating patients with kidney disease. The birth of automated
      urine analysis technology and centralized laboratory testing has unfortunately
      made examination of urine sediment by physicians a rare event. At the same time,
      identifying novel urine biomarkers for kidney disease has become a research
      priority in nephrology, and the search for the "renal troponin" has progressed at
      a fast pace. Despite this, urine sediment examination remains a time-honored test
      that provides a wealth of information about the patient's kidney condition and
      performs favorably as a urinary biomarker. It alerts the clinician to the
      presence of kidney disease and provides diagnostic information that often
      identifies the compartment of kidney injury. In addition, sediment findings may
      guide therapy and assist in prognostication. As such, it is premature to abandon
      urine sediment examination. It may be more appropriate to combine urine sediment
      examination with new candidate biomarkers that enter clinical practice to create
      a "diagnostic panel" that provides clinicians with a useful battery of diagnostic
      tests. To accomplish this, we as nephrologists must encourage continued training
      and maintenance of competency in urine sediment examination. 

PMID- 25943717
TI  - A Meta-analysis of the Association of Estimated GFR, Albuminuria, Age, Race, and
      Sex With Acute Kidney Injury.
AB  - BACKGROUND: Acute kidney injury (AKI) is a serious global public health problem.
      We aimed to quantify the risk of AKI associated with estimated glomerular
      filtration rate (eGFR), albuminuria (albumin-creatinine ratio [ACR]), age, sex,
      and race (African American and white). STUDY DESIGN: Collaborative meta-analysis.
      SETTING & POPULATION: 8 general-population cohorts (1,285,049 participants) and 5
      chronic kidney disease (CKD) cohorts (79,519 participants). SELECTION CRITERIA
      FOR STUDIES: Available eGFR, ACR, and 50 or more AKI events. PREDICTORS: Age,
      sex, race, eGFR, urine ACR, and interactions. OUTCOME: Hospitalized with or for
      AKI, using Cox proportional hazards models to estimate HRs of AKI and random
      effects meta-analysis to pool results. RESULTS: 16,480 (1.3%) general-population
      cohort participants had AKI over a mean follow-up of 4 years; 2,087 (2.6%) CKD
      participants had AKI over a mean follow-up of 1 year. Lower eGFR and higher ACR
      were strongly associated with AKI. Compared with eGFR of 80mL/min/1.73m(2), the
      adjusted HR of AKI at eGFR of 45mL/min/1.73m(2) was 3.35 (95% CI, 2.75-4.07).
      Compared with ACR of 5mg/g, the risk of AKI at ACR of 300mg/g was 2.73 (95% CI,
      2.18-3.43). Older age was associated with higher risk of AKI, but this effect was
      attenuated with lower eGFR or higher ACR. Male sex was associated with higher
      risk of AKI, with a slight attenuation in lower eGFR but not in higher ACR.
      African Americans had higher AKI risk at higher levels of eGFR and most levels of
      ACR. LIMITATIONS: Only 2 general-population cohorts could contribute to analyses
      by race; AKI identified by diagnostic code. CONCLUSIONS: Reduced eGFR and
      increased ACR are consistent strong risk factors for AKI, whereas associations of
      AKI with age, sex, and race may be weaker in more advanced stages of CKD.

PMID- 25943720
TI  - Is there an androgen level threshold for aneuploidy risk in infertile women?
AB  - BACKGROUND: Low functional ovarian reserve (LFOR) has been associated with
      hypoandrogenemia and increased embryo aneuploidy, while androgen supplementation
      has been reported to improve aneuploidy rates. We, therefore, assessed whether in
      infertile women undergoing in vitro fertilization (IVF) androgen concentrations
      are associated with aneuploidy rates. METHODS: This study was performed in 2
      academically affiliated fertility centers in New York City and an academically
      affiliated steroid chemistry laboratory in Utah. Androgen concentrations were
      measured in blinded fashion from 84 infertile women (age 40.3+/-2.4 years) at New
      York University (NYU), using a validated LC-MS/MS method, in cryopreserved serum
      samples of patients who had undergone IVF with concomitant preimplantation
      genetic screening (PGS), utilizing a 24-chromosome platform. The Center for Human
      Reproduction (CHR) provided plasma samples of 100 historical controls (ages
      38.6+/-5.0 years) undergoing IVF without PGS. Statistical comparisons were made
      of androgen concentrations, and of associations between androgen concentrations
      and embryo aneuploidy. RESULTS: Women undergoing IVF+PGS at NYU revealed no
      association between embryo aneuploidy and androgen concentrations but
      demonstrated significantly lower androgen concentrations than the 100 control
      patients from CHR, CONCLUSIONS: Though this study revealed no association between
      androgen levels and embryo ploidy, the extremely low androgen levels in the NYU
      study group raise the possibility of a threshold effect below which testosterone
      no longer affects aneuploidy. Before an androgen effect on embryo ploidy can be
      completely ruled out, a patient population with more normal androgen levels has
      to be investigated.

PMID- 25943721
TI  - Predonation Direct and Indirect Costs Incurred by Adults Who Donated a Kidney:
      Findings From the KDOC Study.
AB  - Limited information exists on the predonation costs incurred by eventual living
      kidney donors (LKDs). Expenses related to completion of the donation evaluation
      were collected from 194 LKDs participating in the multi-center, prospective
      Kidney Donor Outcomes Cohort (KDOC) Study. Most LKDs (n = 187, 96%) reported one
      or more direct costs, including ground transportation (80%), healthcare (24%),
      lodging (17%) and air transportation (14%), totaling $101 484 (USD; mean = $523
      +/- 942). Excluding paid vacation or sick leave, donor and companion lost wages
      totaled $35 918 (mean = $187 +/- 556) and $14 378 (mean = $76 +/- 311),
      respectively. One-third of LKDs used paid vacation or sick leave to avoid
      incurring lost wages. Few LKDs reported receiving financial support from the
      transplant candidate (6%), transplant candidate's family (3%), a nonprofit
      organization (3%), the National Living Donor Assistance Center (7%), or
      transplant center (3%). Higher total costs were significantly associated with
      longer distance traveled to the transplant center (p < 0.001); however, total
      costs were not associated with age, sex, race/ethnicity, household income,
      marital status, insurance status, or transplant center. Moderate predonation
      direct and indirect costs are common for adults who complete the donation
      evaluation. Potential LKDs should be advised of these possible costs, and the
      transplant community should examine additional strategies to reimburse donors for
      them.

PMID- 25943722
TI  - Drug delivery from gelatin-based systems.
AB  - INTRODUCTION: Carriers for controlled drug release offer many advantages compared
      with conventional dosage forms. Gelatin has been investigated extensively as a
      drug delivery carrier, due to its properties and history of safe use in a wide
      range of medical applications. AREAS COVERED: Gelatin was shown to be versatile
      due to its intrinsic features that enable the design of different carrier
      systems, such as microparticles and nanoparticles, fibers and even hydrogels.
      Gelatin microparticles can serve as vehicles for cell amplification and for
      delivery of large bioactive molecules, whereas gelatin nanoparticles are better
      suited for intravenous delivery or for drug delivery to the brain. Gelatin fibers
      contain a high surface area-to-volume ratio, whereas gelatin hydrogels can trap
      molecules between the polymer's crosslink gaps, allowing these molecules to
      diffuse into the blood stream. Another interesting area is the combination of
      tissue bioadhesive-based gelatin with controlled drug release for pain management
      and wound healing. EXPERT OPINION: The modification of gelatin and its
      combinations with other biomaterials have demonstrated the flexibility of these
      systems and can be employed for meeting the challenges of finding ideal carrier
      systems that enable specific, targeted and controlled release in response to
      demands in the body.

PMID- 25943723
TI  - The chorion ultrastructure of ova of Lophius spp.
AB  - The chorion surface ultrastructure of unfertilized eggs of black anglerfish
      Lophius budegassa and white anglerfish Lophius piscatorius was examined by
      scanning electron microscopy. Species-specific differences were observed. 

PMID- 25943725
TI  - Retinal Nerve Fiber Layer Converges More Convexly on Normal Smaller Optic Nerve
      Head.
AB  - PURPOSE: To investigate retinal nerve fiber layer (RNFL) configuration in the
      optic nerve head (ONH) and peripapillary area according to disc size and to
      determine whether it explains cup discrepancy among eyes with different disc
      sizes. METHODS: Horizontal and vertical RNFL curvature and mean thickness were
      measured using confocal scanning laser ophthalmoscopy (Heidelberg Retina
      Tomograph) in 63 normal subjects grouped by disc size. Average and quadrant RNFL
      thickness, disc size, average cup-to-disc ratio (CDR), and convergence angle at
      the optic disc were also measured using Cirrus HD-optical coherence tomography.
      The relationships between disc size and RNFL curvature, thickness, angle at optic
      disc, and CDR were evaluated. RNFL curvature and convergence angle reflects
      convexity "on" and "into" the optic disc, respectively. RESULTS: CDR was smaller
      for small discs and was positively correlated with disc size (P<0.001).
      Horizontal and vertical RNFL curvatures were significantly more convex for small
      than large discs (P=0.001, 0.017). Horizontal and vertical RNFL angles at the
      optic disc were positively correlated with disc size (P<0.001, P=0.012). Optic
      disc area was negatively correlated with mean RNFL thickness at the optic disc
      margin measured by HRT (P=0.002), but not in the peripapillary area by optical
      coherence tomography. CONCLUSIONS: Using imaging techniques, we demonstrated that
      the shape of the RNFLs converging "on" and entering "into" the optic disc was
      more convex for small optic discs compared with large discs. A low CDR for small
      discs could be mediated by these RNFL profiles at the ONH, which may guide the
      clinical evaluation of glaucomatous ONH damage.

PMID- 25943724
TI  - Therapeutic radiotherapy for giant cell tumor of the spine: a systemic review.
AB  - BACKGROUND: Giant cell tumor of the bone (GCTB) is a benign but locally
      aggressive tumor. Giant cell tumor of the spine (GCTS) accounts for 3-6 % of
      GCTB. Surgery remains the treatment of choice. For those not suitable for
      surgery, therapeutic radiotherapy (RT) is one classic modality. Although there
      are several articles on therapeutic RT for GCTS therapy, few systemic reviews
      have been performed on effects of therapeutic RT on GCTS. METHODS AND MATERIALS:
      We searched EMBASE and Medline databases for papers reporting therapeutic
      radiotherapy for GCTS patients not suitable for surgical resection. The inclusion
      criteria and prognosis indicators have been defined prior to data extraction.
      Information of the included patients has been discreetly recorded. We analyzed
      the prognosis of therapeutic RT and multiple data concerning the GCTS patients.
      The indicators for prognosis were computed by SPSS software. The local control
      (LC) and overall survival (OS) rate was estimated by the Kaplan-Meier method. p
      values <=0.5 were considered statistically significant. RESULT: We included 13
      studies comprising 42 patients who received therapeutic radiotherapy with doses
      ranging from 21 to 80 Gy. The results suggested a response rate of 100 %, OS of
      97.6 %, 1-year local control rate (LC) of 85.4 %, 2-year LC rate of 80.2 %, and
      overall LC of 79 %. No patient reported malignant transformation albeit four had
      post-RT neurological complications. Four had distant metastasis of the tumor.
      Patients with previously repeated recurrence had worse prognosis after RT (p =
      0.028). No association between dosage and prognosis was found. CONCLUSION:
      Therapeutic RT could provide a satisfactory prognosis for GCTS patients according
      to this study, and can be an alternative treatment modality for GCTS patients not
      suitable for surgery.

PMID- 25943726
TI  - Structural Differences in the Optic Nerve Head of Glaucoma Patients With and
      Without Disc Hemorrhages.
AB  - PURPOSE: The aim of the study was to evaluate differences in planimetry, optic
      nerve parameters, and visual field (VF) indices in glaucomatous eyes with a disc
      hemorrhage (DH), their contralateral counterparts without DH, and normal
      controls. PATIENTS AND METHODS: We retrospectively reviewed the records (from
      1995 to 2013) of 44 glaucoma subjects with unilateral DH and 50 normal controls.
      In the DH group, 33 had bilateral fundus photos for planimetric analysis
      (Cyoptique GL), 15 had spectral domain-optical coherence tomography (SD-OCT), 15
      had VF indices (Humphrey Visual Field Analyser), and 39 had >= 5 perimetry
      outputs for progression analysis (Progressor). RESULTS: Structurally, planimetric
      analysis revealed that the eye with DH had a larger cup-disc ratio, more
      significantly in the vertical aspect (P<0.001), and a thinner rim (P=0.010),
      compared with the contralateral eye without DH. SD-OCT analysis also showed a
      thinner rim area (P<0.001), most significantly in 2, 3, and 9 clock hours and the
      inferior and superior quadrants (P<0.001) compared with the contralateral eye
      without DH and normal controls. Also, the vertical cup-disc ratio was larger
      (P<0.001). Functionally, VF deterioration was demonstrated by VF indices in eyes
      with DH-mean deviation: -10.69 versus -0.97, P<0.001 and pattern standard
      deviation: 6.60 versus 1.59, P<0.001, compared with normal controls. CONCLUSIONS:
      Eyes with DH consistently displayed both structural features of more advanced
      glaucoma confirmed simultaneously on planimetry and SD-OCT, with concurrent VF
      deterioration.

PMID- 25943727
TI  - Plateau Iris in Primary Angle Closure Glaucoma: An Ultrasound Biomicroscopy
      Study.
AB  - PURPOSE: To determine prevalence and anterior segment morphology of plateau iris
      in patients with primary angle closure glaucoma (PACG) after laser peripheral
      iridotomy using ultrasound biomicroscopy (UBM). METHODS: In this prospective
      study, 262 PACG patients and 144 normal controls underwent UBM examination.
      Plateau iris in a quadrant was defined by the presence of anteriorly directed
      ciliary process, absent ciliary sulcus, steep iris root from its point of
      insertion followed by a downward angulation, flat iris plane, and irido-angle
      contact in the same quadrant. At least 2 quadrants had to fulfill these UBM
      criteria. RESULTS: UBM analysis showed plateau iris in 83/262 (31.68%, 95%
      confidence interval: 26.7%-37.9%) PACG eyes, it was common in female individuals
      (61.44%), and patients were significantly younger than PACG patients (P=0.006).
      Plateau iris was found in superior quadrant in 19/83 (22.89%) eyes, inferior
      quadrant in 19/83 (22.89%) eyes, nasal quadrant in 21/83 (25.3%) eyes, and
      temporal quadrant in 24/83 (28.91%) eyes. In plateau iris patients, the central
      anterior chamber depth was shallower, the anterior chamber angle, the scleral
      iris angle, and the sclera-ciliary process angle were significantly narrower, and
      the trabecular ciliary process distance and the iris ciliary process distance
      were significantly shorter in patients than in PACG subjects. CONCLUSIONS:
      Patients with plateau iris had significantly shallow central ACD when compared
      with those with pupillary block and normal eyes. After laser peripheral
      iridotomy, about a third of PACG eyes had plateau iris. This is clinically
      important because these patients can develop synechial angle closure and should
      be followed up closely.

PMID- 25943728
TI  - Icare ONE Home Tonometry in Children With and Without Known Glaucoma.
AB  - PURPOSE: The Icare ONE (Finland Oy) rebound tonometer may have promise for home
      tonometry in children with glaucoma. The purpose of this study was: (1) to assess
      the feasibility of Icare ONE home tonometry in a small number of children with
      and without glaucoma and (2) to characterize diurnal intraocular pressure (IOP)
      variations in children with and without glaucoma. METHODS: Patients were
      recruited from Duke pediatric ophthalmology clinic. Parents underwent in-clinic
      training for Icare ONE tonometry. Parents were instructed to record the subject's
      IOP using Icare ONE at 6 time intervals daily for 10 sequential days. RESULTS:
      Eight normal subjects (16 eyes) and 10 subjects (10 eyes) with glaucoma were
      included. All parents successfully performed Icare ONE home tonometry. In-clinic
      Icare ONE IOP exceeded Goldmann applanation in both groups. Normal subjects (mean
      age, 11.8 y) had a mean daily IOP range of 4.8 +/- 4.6 mm Hg for right eyes and
      5.2 +/- 1.7 mm Hg for left eyes, and demonstrated relative peaks in the morning
      and relative troughs in the evening. Subjects with glaucoma (mean age, 12.4 y)
      had a mean daily IOP range of 8.6 +/- 8.2 mm Hg, and demonstrated an even
      distribution of relative peaks and troughs throughout the day. CONCLUSIONS: Icare
      ONE home tonometry seems feasible in a small number of children. Normal eyes
      demonstrated smaller daily IOP ranges than glaucomatous eyes. Normal eyes were
      also more likely to show a relative early morning IOP peak and a late evening IOP
      trough. It is likely that the limited sampling in this study limits its
      generalizability to all children with glaucoma or to normal children.

PMID- 25943729
TI  - Diagnostic Abilities of Variable and Enhanced Corneal Compensation Algorithms of
      GDx in Different Severities of Glaucoma.
AB  - PURPOSE: To compare the abilities of retinal nerve fiber layer (RNFL) parameters
      of variable corneal compensation (VCC) and enhanced corneal compensation (ECC)
      algorithms of scanning laser polarimetry (GDx) in detecting various severities of
      glaucoma. METHODS: Two hundred and eighty-five eyes of 194 subjects from the
      Longitudinal Glaucoma Evaluation Study who underwent GDx VCC and ECC imaging were
      evaluated. Abilities of RNFL parameters of GDx VCC and ECC to diagnose glaucoma
      were compared using area under receiver operating characteristic curves (AUC),
      sensitivities at fixed specificities, and likelihood ratios. RESULTS: After
      excluding 5 eyes that failed to satisfy manufacturer-recommended quality
      parameters with ECC and 68 with VCC, 56 eyes of 41 normal subjects and 161 eyes
      of 121 glaucoma patients [36 eyes with preperimetric glaucoma, 52 eyes with early
      (MD>-6 dB), 34 with moderate (MD between -6 and -12 dB), and 39 with severe
      glaucoma (MD<-12 dB)] were included for the analysis. Inferior RNFL, average
      RNFL, and nerve fiber indicator parameters showed the best AUCs and sensitivities
      both with GDx VCC and ECC in diagnosing all severities of glaucoma. AUCs and
      sensitivities of all RNFL parameters were comparable between the VCC and ECC
      algorithms (P>0.20 for all comparisons). Likelihood ratios associated with the
      diagnostic categorization of RNFL parameters were comparable between the VCC and
      ECC algorithms. CONCLUSION: In scans satisfying the manufacturer-recommended
      quality parameters, which were significantly greater with ECC than VCC algorithm,
      diagnostic abilities of GDx ECC and VCC in glaucoma were similar.

PMID- 25943730
TI  - Drug-induced Bilateral Secondary Angle-Closure Glaucoma: A Literature Synthesis.
AB  - PURPOSE: We performed a literature synthesis to identify the full spectrum of
      compounds implicated in drug-induced, bilateral secondary angle-closure glaucoma
      (2 degrees  ACG). METHODS: Systematic PubMed literature review identified
      relevant bilateral 2 degrees  ACG case reports. We evaluated these reports with
      both the Naranjo adverse drug reaction probability scale to assess the causality
      of reported drug reactions and a 2 degrees  ACG scale scoring system we developed
      to determine the likelihood that the event represented bilateral 2 degrees  ACG.
      Two independent graders performed these analyses and their scores were averaged
      for interpretation. The Naranjo scale ranges from -4 to +13 and the drug reaction
      was considered definite if the score was >= 9, probable if 5 to 8, possible if 1
      to 4, and doubtful if <= 0. The 2 degrees  ACG score ranges from 0 to 7. We
      considered a 2 degrees  ACG score of >= 4 as evidence of significant likelihood
      that the drug reaction represented bilateral 2 degrees  ACG. RESULTS: No drug had
      a definite Naranjo score, but the following drug entities had probable Naranjo
      scores and 2 degrees  ACG scores >= 4: acetazolamide, "anorexiant mix,"
      bupropion, cabergoline, "ecstasy," escitalopram, flavoxate, flucloxacillin,
      hydrochlorothiazide, hydrochlorothiazide/triamterene, mefenamic acid,
      methazolamide, oseltamivir, topiramate, topiramate/bactrim, and venlafaxine. Root
      chemical analysis revealed that sulfur-containing and non-sulfur-containing
      compounds contributed to bilateral 2 degrees  ACG. CONCLUSIONS: Several compound
      preparations were implicated in drug-induced bilateral 2 degrees  ACG. Treating
      physicians should be aware that some forms of recreational drug use, which the
      patient may not admit to, could contribute to this vision-threatening side
      effect.

PMID- 25943731
TI  - Outcomes of Primary Trabeculectomy With Mitomycin-C in Glaucoma Secondary to
      Iridocorneal Endothelial Syndrome.
AB  - PURPOSE: To report the outcomes of primary trabeculectomy with mitomycin-C (MMC)
      in eyes with glaucoma secondary to iridocorneal endothelial (ICE) syndrome.
      METHODS: We included 16 eyes of 15 subjects with ICE syndrome who underwent
      primary trabeculectomy with MMC between 1991 and 2013. Surgical success was
      defined as complete when the intraocular pressure (IOP) was >=5 and <=21 mm Hg
      with no additional antiglaucoma medication (AGM) or surgery and as qualified if
      IOP was controlled with AGM. RESULTS: The median age (interquartile range) of
      subjects at the time of trabeculectomy was 41 years (37, 44 y) and the median
      follow-up period was 23 months (7, 79 mo). Postoperatively, the median IOP
      significantly reduced from 36 (26, 43) to 14 mm Hg (12, 17 mm Hg) (P<0.001) and
      median number of AGMs reduced from 3 (2, 4) to 0 (0, 0) (P<0.001). The percentage
      of complete success was 75% at 6 months, 64% at 12 months, 57% at 36 months, and
      33% at 60 months. The percentage of qualified success was 94% at 6 months, 82% at
      12 months, 71% at 36 months, and 60% at 60 months. Five eyes failed during the
      follow-up period. The mean (+/-SD) number of glaucoma surgeries per eye was 1.3+/
      0.5. Eight eyes developed corneal edema at a median follow-up of 78.5 months and
      4 eyes underwent keratoplasty. CONCLUSIONS: Primary trabeculectomy with MMC
      offers moderate surgical success in patients with ICE syndrome. Maintaining long
      term IOP control and corneal clarity in these eyes is a big challenge.

PMID- 25943732
TI  - Anterior Chamber Angle and Intraocular Pressure Changes After
      Phacoemulsification: A Comparison Between Eyes With Closed-angle and Open-angle
      Glaucoma.
AB  - PURPOSE: To compare the angle and intraocular pressure (IOP) changes after
      phacoemulsification between eyes with closed-angle or open-angle glaucoma.
      METHODS: Angle measurements using Visante AS-OCT imaging was performed for a
      prospective cohort of 24 subjects with closed-angle and 30 subjects with open
      angle glaucoma before and 3 months after phacoemulsification. IOP measurement was
      measured at 6 and 12 months after surgery using Goldmann applanation tonometry as
      secondary outcome measures. RESULTS: Eyes with closed angles were smaller than
      those with open angles (mean axial length 22.88 vs. 24.11 mm, P<0.001). Mean
      anterior chamber depth, area, volume, AOD500, AOD750, ARA, TISA500, and TISA750
      increased after phacoemulsification in all eyes regardless of preexisting angle
      status (all P<0.001). Increase in AOD500, AOD750, TISA500, and TISA750 were
      greater in eyes with open angles compared with closed angles (P=0.03, 0.04. 0.04,
      0.04, respectively). Mean IOP decreased by 1.8 and 2.1 mm Hg at 6 and 12 months,
      respectively, after phacoemulsification for all eyes (P<0.001 for both timepoints
      compared with preoperative baseline). However, postoperative reduction in the
      mean IOP was not significantly different between eyes with closed and open angles
      (Mann-Whitney test P=0.32 at 6 mo and P=0.75 at 12 mo postsurgery compared with
      preoperative). CONCLUSIONS: Angle opening postphacoemulsification was
      considerable in all eyes. A similar IOP reduction after phacoemulsification was
      observed in all eyes regardless of angle status.

PMID- 25943733
TI  - Technique for Tube Extender Implantation.
AB  - PURPOSE: To describe a novel technique to facilitate Tube Extender implantation.
      MATERIALS AND METHODS: Two Tube Extender implantations were performed on 2 eyes
      of 2 patients. RESULTS: Before implanting the Tube Extender onto the cut tube of
      the glaucoma drainage device, a 30-G cannula, coated with viscoelastic, is
      threaded through the distal end of the extender and emerges from the proximal
      end. The cannula, with the extender laced over it, is then inserted into the cut
      tube, and the surgeon slides the Tube Extender down the cannula for insertion
      onto the cut tube. CONCLUSIONS: Retraction of the glaucoma drainage device from
      the anterior chamber occurs for various reasons, often the growth of the globe in
      pediatric patients. Tube Extenders can be implanted to lengthen the glaucoma
      drainage device to reenter the anterior chamber. However, the surgical technique
      can often be technically difficult to perform due to the flexibility of the
      glaucoma drainage device tube. We present a novel technique for Tube Extender
      implantation that makes the procedure easier to perform.

PMID- 25943734
TI  - No Evidence of Association of Heterozygous Galactosylceramidase Deletion With
      Normal-Tension Glaucoma in a Korean Population.
AB  - PURPOSE: A significant association between primary open-angle glaucoma risk and
      copy-number variation in the galactosylceramidase (GALC) gene was reported
      recently. This study investigated whether a heterozygous deletion of the GALC
      gene plays a significant role in normal-tension glaucoma (NTG) in Koreans.
      METHODS: A 3-primer polymerase chain reaction assay was used to examine the
      heterozygous deletion of GALC in all Korean NTG cases (n=276) and controls
      (n=135). RESULTS: We did not identify any deletion variant of GALC gene in the
      NTG patients. CONCLUSIONS: This is the first copy-number variation study of the
      GALC gene in the Korean population with NTG. We demonstrated that a heterozygous
      GALC deletion does not play a significant role in the pathogenesis of NTG in a
      representative clinic-based population of South Koreans, unlike whites.

PMID- 25943735
TI  - Blebitis After EX-PRESS Glaucoma Filtration Device Implantation-A Case Series.
AB  - PURPOSE: To present the management and outcomes of blebitis in patients who
      underwent EX-PRESS Glaucoma Filtration Device (GFD) implantation. DESIGN:
      Retrospective case series. PARTICIPANTS: The study included 5 patients who
      developed blebitis following EX-PRESS GFD implantation. METHODS: Charts of all
      patients who underwent EX-PRESS GFD implantation at the Glaucoma Center of San
      Francisco between 2007 and 2013 were reviewed. Five patients with blebitis were
      identified and their clinical course was recorded. MAIN OUTCOME MEASURES:
      Clinical course of blebitis. RESULTS: Of 325 eyes that underwent EX-PRESS GFD
      implantation, 5 eyes (1.5%) with blebitis were identified. The mean interval
      between EX-PRESS GFD surgery and blebitis was 2.3+/-0.8 years. Four of the 5 eyes
      with blebitis had potential risk factors for bleb-related infection; 1 had
      chronic blepharitis, 2 had contact lens use, and one had 2 episodes of bleb leak
      before blebitis. All patients were treated with topical antibiotics; in addition,
      3 received oral antibiotics and 1 received intravitreal antibiotics. None of the
      patients developed endophthalmitis. One patient had recurrent blebitis, which was
      treated with topical, oral, and intravitreal antibiotics. None of the patients
      had the device removed. The mean follow-up time after blebitis was 16.8+/-8.9
      months (range, 10 to 32 mo). CONCLUSIONS: This case series suggests that blebitis
      after EX-PRESS GFD implanted under a scleral flap may be treated without removal
      of the device. Further study is required to determine the optimal method of
      treating this condition.

PMID- 25943736
TI  - Endophthalmitis Trends and Outcomes Following Glaucoma Surgery at a Tertiary Eye
      Care Hospital in Saudi Arabia.
AB  - PURPOSE: To compare the incidence, microbial profile, management and outcomes of
      endophthalmitis after glaucoma drainage implant (GDI), or trabeculectomy over 2
      separate time periods before and after the year 2000. METHODS: A chart review was
      performed for patients with endophthalmitis after trabeculectomy (trabeculectomy
      group) or GDI group between 1983 to 1999 (group 1) and 2000 to 2011 (group 2) at
      a tertiary care hospital. Data were compared between groups and time periods.
      RESULTS: There were 56 cases of endophthalmitis after trabeculectomy in group 1
      and 17 cases in group 2. After GDI, there were 10 cases of endophthalmitis in
      group 1 and 1 case in group 2. The incidence of endophthalmitis after GDI
      decreased significantly from 0.0105% to 0.00074% in groups 1 and 2, respectively
      (P<0.05). The incidence of endophthalmitis decreased significantly after
      trabeculectomy from 0.007% in group 1 to 0.00197% in group 2 (P=0.0004). There
      were 26 culture-positive cases in group 1 and 10 in group 2. The most common
      isolates were Streptococcus species in group 1 and Staphylococcus species in
      group 2. Indicators of morbidity were lower in group 2. The final visual outcome
      in either group was not correlated to the type of surgery, microbes, or initial
      management. CONCLUSIONS: There was a greater incidence of endophthalmitis after
      trabeculectomy compared with GDI. The incidence of endophthalmitis decreased from
      2001 to 2011 compared with 1983 to 1999, which is likely due to advances in
      surgical technique. However, significant visual morbidity does occur despite
      prompt treatment.

PMID- 25943737
TI  - Choroidal Thickness and Open-Angle Glaucoma: A Meta-Analysis and Systematic
      Review.
AB  - PURPOSE: Numerous studies have detected choroidal thickness abnormalities and
      changes in open-angle glaucoma (OAG), as measured by enhanced depth imaging
      optical coherence tomography technologies, but the results have not always been
      consistent. Therefore, a meta-analysis and systematic review was performed to
      evaluate the choroidal thickness in OAG. MATERIALS AND METHODS: A comprehensive
      literature search was performed on Medline, Embase, ISI Web of Science, Cochrane
      Central Register of Controlled Trials, Google Scholar, and Chinese databases
      including Wangfang and CNKI (China National Knowledge Infrastructure). Eligible
      articles were identified by reviewing the retrieved results. For continuous
      outcomes, we calculated the weighted mean difference (WMD) and 95% confidence
      interval (CI). Statistical analysis was performed using STATA 12.0 software.
      RESULTS: Twenty-two case-control or cross-sectional studies were included in the
      present meta-analysis. The results of our study showed that there was no
      significant difference in subfoveal choroidal thickness between patients with OAG
      and controls (WMD=-7.94; 95% CI, -26.01 to 10.13; P=0.389). Similar findings were
      obtained for the average peripapillary choroidal thickness (WMD=-14.24; 95% CI, 
      30.20 to 1.73; P=0.08). CONCLUSIONS: Our meta-analysis found no significant
      difference in the choroidal thickness both under the fovea and around the optic
      nerve head between OAG patients and controls. On the basis of the anatomic
      features of blood supply in optic nerve head, it is plausible that the choroidal
      thickness is not an appropriate parameter to evaluate the damage of OAG, and
      choroidal thinning may not be an important component of glaucomatous optic
      neuropathy.

PMID- 25943738
TI  - The Impact of Lens Vault on Visual Acuity and Refractive Error: Implications for
      Management of Primary Angle-closure Glaucoma.
AB  - PURPOSE: To investigate the relationship between lens vault (LV), visual acuity
      (VA), and refraction. METHODS: This was a cross-sectional study of 2047 subjects
      aged 50 years and older recruited from a community polyclinic. Anterior segment
      optical coherence tomography was performed, and customized software was used to
      measure LV. VA was measured using a logarithm of minimum angle of resolution
      chart (logMAR chart; Lighthouse Inc.), and was classified as normal (logMAR<0.3),
      mild impairment (0.3<logMAR<0.6), and moderate/severe impairment (logMAR>0.6).
      Refraction was measured with an autorefractor machine and spherical equivalent
      was defined as sphere plus half cylinder. Angle closure was defined as posterior
      trabecular meshwork not visible for >=2 quadrants on nonindentation gonioscopy.
      RESULTS: Complete data were available for 1372 subjects including 295 (21.5%)
      with angle closure. Angle-closure subjects were significantly older (P<0.001),
      with shorter axial length (P<0.001), shallower anterior chamber depth (P<0.001),
      and greater LV (P<0.001). There was no significant difference in VA (P=0.12)
      compared with those without angle closure. After adjusting for age, sex, axial
      length, anterior chamber depth, and spherical equivalent, there was no
      significant association between LV and VA (P=0.35) or between LV and spherical
      equivalent (P=0.06). CONCLUSIONS: The magnitude of LV was not associated with VA
      or spherical equivalent. Lens extraction may be a consideration in eyes with
      angle closure with large LV in the absence of visually significant cataract.

PMID- 25943739
TI  - Development of Glaucomatous Visual Field Defects in Preperimetric Glaucoma
      Patients Within 3 Years of Diagnosis.
AB  - PURPOSE: To determine the characteristics of eyes diagnosed with preperimetric
      glaucoma (PPG) that developed glaucomatous visual field defects (VFDs) within 3
      years of the diagnosis. PATIENTS AND METHODS: The medical charts of 77 eyes of 77
      patients with PPG were reviewed. An eye was diagnosed with PPG when there was
      neuroretinal rim thinning, cupping of the optic disc, or a suspicious retinal
      nerve fiber layer (RNFL) defect, and had no conditions fulfilling Anderson's
      criteria for glaucoma. The Central 30-2 SITA-Standard program of the Humphrey
      Field Analyzer was used to determine the presence of VFDs and the thicknesses of
      the retinal layers was determined by spectral-domain optical coherence
      tomography. RESULTS: Ten of the 77 patients with PPG (13.0%) developed
      glaucomatous VFD. These 10 eyes had significantly thinner macular ganglion cell
      and inner plexiform layer (mGCIPL) thickness in the inferior and inferotemporal
      sectors, and also the circumpapillary retinal nerve fiber layer (cpRNFL)
      thickness at the 7 or 8 o'clock sectors. In the 3 years post-PPG period, these
      eyes had significant decreases in the mGCIPL thickness of all the inferior
      sectors, and cpRNFL at the 7 or 8 o'clock sectors. The mean intraocular pressure
      in eyes with VFDs (15.2+/-2.0 mm Hg) was significantly higher than that in those
      without VFDs (13.5+/-2.6 mm Hg; P=0.042). CONCLUSIONS: Significant structural
      changes were observed in the mGCIPL and cpRNFL at PPG diagnosis, before the
      development of a VFDs. Close monitoring of intraocular pressure is essential for
      the appropriate management of PPG.

PMID- 25943741
TI  - Is Daylight-PDT a good treatment option during solar eclipse?

PMID- 25943740
TI  - Decline in arylsulfatase B and Increase in chondroitin 4-sulfotransferase combine
      to increase chondroitin 4-sulfate in traumatic brain injury.
AB  - In an established rat model of penetrating ballistic-like brain injury (PBBI),
      arylsulfatase B (ARSB; N-acetylgalactosamine 4-sulfatase) activity was
      significantly reduced at the ipsilateral site of injury, but unaffected at the
      contralateral site or in sham controls. In addition, the ARSB substrate
      chondroitin 4-sulfate (C4S) and total sulfated glycosaminoglycans increased. The
      mRNA expression of chondroitin 4-sulfotransferase 1 (C4ST1; CHST11) and the
      sulfotransferase activity rose at the ipsilateral site of injury (PBBI-I),
      indicating contributions from both increased production and reduced degradation
      to the accumulation of C4S. In cultured, fetal rat astrocytes, following scratch
      injury, the ARSB activity declined and the nuclear hypoxia inducible factor
      1alpha increased significantly. In contrast, sulfotransferase activity and
      chondroitin 4-sulfotransferase expression increased following astrocyte exposure
      to TGF-beta1, but not following scratch. These different pathways by which C4S
      increased in the cell preparations were both evident in the response to injury in
      the PBBI-I model. Hence, findings support effects of injury because of mechanical
      disruption inhibiting ARSB and to chemical mediation by TGF-beta1 increasing
      CHST11 expression and sulfotransferase activity. The increase in C4S following
      traumatic brain injury is because of contributions from impaired degradation and
      enhanced synthesis of C4S which combine in the pathogenesis of the glial scar.
      This is the first report of how two mechanisms contribute to the increase in
      chondroitin 4-sulfate (C4S) in TBI. Following penetrating ballistic-like brain
      injury in a rat model and in the scratch model of injury in fetal rat astrocytes,
      Arylsulfatase B activity declined, leading to accumulation of C4S. TGF-beta1
      exposure increased expression of chondroitin 4-sulfotransferase. Hence, the
      increase in C4S in TBI is attributable to both impaired degradation and enhanced
      synthesis, combining in the pathogenesis of the glial scar. 

PMID- 25943742
TI  - Crystallization and preliminary X-ray crystallographic study of a 3.8-MDa
      respiratory supermolecule hemocyanin.
AB  - Many molluscs transport oxygen using a very large cylindrical multimeric copper
      containing protein named hemocyanin. The molluscan hemocyanin forms a decamer
      (cephalopods) or multidecamer (gastropods) of approximately 330-450kDa subunits,
      resulting in a molecular mass >3.3MDa. Therefore, molluscan hemocyanin is one of
      the largest proteins. The reason why these organisms use such a large
      supermolecule for oxygen transport remains unclear. Atomic-resolution X-ray
      crystallographic analysis is necessary to unveil the detailed molecular structure
      of this mysterious large molecule. However, its propensity to dissociate in
      solution has hampered the crystallization of its intact form. In the present
      study, we successfully obtained the first crystals of an intact decameric
      molluscan hemocyanin. The diffraction dataset at 3.0-A resolution was collected
      by merging the datasets of two isomorphic crystals. Electron microscopy analysis
      of the dissolved crystals revealed cylindrical particles. Furthermore, self
      rotation function analysis clearly showed the presence of a fivefold symmetry
      with several twofold symmetries perpendicular to the fivefold axis. The
      absorption spectrum of the crystals showed an absorption peak around 345nm. These
      results indicated that the crystals contain intact hemocyanin decamers in the
      oxygen-bound form. 

PMID- 25943743
TI  - Increasing Efforts to Reduce Cervical Cancer through State-Level Comprehensive
      Cancer Control Planning.
AB  - Reducing cervical cancer disparities in the United States requires intentional
      focus on structural barriers such as systems and policy that impact access to
      human papillomavirus (HPV) vaccination, cervical cancer screening, and treatment.
      Such changes are difficult and often politicized. State comprehensive cancer
      control (CCC) plans are vehicles that, if designed well, can help build
      collective focus on structural changes. Study objectives were to identify the
      prioritization of cervical cancer in state CCC plans, the conceptualization of
      HPV within these plans, and the focus of plans on structural changes to reduce
      cervical cancer disparities. Data were gathered by systematic content analysis of
      CCC plans from 50 states and the District of Columbia from February-June 2014 for
      evidence of cervical cancer prioritization, conceptualization of HPV, and focus
      on structural barriers to cervical cancer vaccination, screening or treatment.
      Findings indicate that prioritization of cervical cancer within state CCC plans
      may not be a strong indicator of state efforts to reduce screening and treatment
      disparities. While a majority of plans reflected scientific evidence that HPV
      causes cervical and other cancers, they did not focus on structural elements
      impacting access to evidence-based interventions. Opportunities exist to improve
      state CCC plans by increasing their focus on structural interventions that impact
      cervical cancer prevention, detection, and treatment, particularly for the 41% of
      plans ending in 2015 and the 31% ending between 2016 and 2020. Future studies
      should focus on the use of policy tools in state CCC plans and their application
      to cervical cancer prevention and treatment.

PMID- 25943744
TI  - Telerehabilitation for persons with multiple sclerosis. A Cochrane review.
AB  - A wide range of telerehabilitation interventions are trialled in persons with
      multiple sclerosis (pwMS). However, the evidence for their effectiveness is
      unclear. Aim of the review was to systematically assess the effectiveness and
      safety of telerehabilitation intervention in pwMS, the types of approaches that
      are effective (setting, type, intensity) and the outcomes (impairment, activity
      limitation and participation) that are affected. The search strategy comprised:
      Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System
      Review Group Specialised Register (up to 9 July, 2014). Relevant journals and
      reference lists of identified studies were screened for additional data. Selected
      studies included randomized and controlled clinical trials that compared
      telerehabilitation intervention/s in pwMS with a control intervention (such as
      lower level or different types of intervention, minimal intervention; waiting
      list controls, no treatment or usual care; interventions given in different
      settings). Best evidence synthesis was based on methodological quality using the
      GRADEpro software. Nine RCTs (N.=531 participants, 469 included in analyses)
      investigated a variety of telerehabilitation interventions in adults with MS. The
      interventions evaluated were complex, with more than one rehabilitation component
      and included physical activity, educational, behavioural and symptom management
      programmes. All studies scored "low" on the methodological quality assessment.
      Evidence from included studies provides 'low-level' evidence for reduction in
      short-term disability (and symptoms) such as fatigue. There was also "low-level"
      evidence supporting telerehabilitation in the longer term for improved functional
      activities, impairments (such as fatigue, pain, insomnia); and participation.
      There were limited data on process evaluation (participants'/therapists'
      satisfaction) and no data available for cost effectiveness. There were no adverse
      events reported as a result of telerehabilitation intervention. There is limited
      evidence to date, on the efficacy of telerehabilitation in improving functional
      activities, fatigue and quality of life in adults with MS. There is also
      insufficient evidence to support what types of telerehabilitation interventions
      are effective, and in which setting. More robust trials are needed to build
      evidence for the clinical and cost effectiveness of these interventions. 

PMID- 25943745
TI  - Rosuvastatin Decreases Mean Platelet Volume in Patients With Diabetes Mellitus.
AB  - Statins have multiple effects (also known as pleiotropic effects) on
      inflammation, plaque stabilization, endothelial function, and hemostasis. We
      evaluated the effects of rosuvastatin on mean platelet volume (MPV)--a marker for
      platelet activity--in patients with diabetes mellitus (DM) on rosuvastatin
      medication. Patients (n = 178) who were to be prescribed high-intensity
      rosuvastatin were retrospectively enrolled according to their medical records.
      Baseline and 6-month biochemical tests, automated blood count, cell-volume
      analysis, and their cardiovascular risk factors were recorded. Rosuvastatin
      significantly reduced the MPV and the lipid parameters including total
      cholesterol, triglyceride, and low-density lipoprotein cholesterol (LDL-C).
      However, there was no correlation between MPV and LDL-C before (r = -.66; P =
      .383) and after (r = -.112; P = .135) rosuvastatin treatment or between DeltaMPV
      and DeltaLDL-C after 40 mg rosuvastatin daily therapy (r = -.155; P = .073).
      Rosuvastatin significantly decreases the MPV as well as cholesterol levels. The
      antiplatelet activation properties of high-dose rosuvastatin treatment in
      patients with DM are not lipid dependent.

PMID- 25943746
TI  - Estimation of the methylation pattern distribution from deep sequencing data.
AB  - BACKGROUND: Bisulphite sequencing enables the detection of cytosine methylation.
      The sequence of the methylation states of cytosines on any given read forms a
      methylation pattern that carries substantially more information than merely
      studying the average methylation level at individual positions. In order to
      understand better the complexity of DNA methylation landscapes in biological
      samples, it is important to study the diversity of these methylation patterns.
      However, the accurate quantification of methylation patterns is subject to
      sequencing errors and spurious signals due to incomplete bisulphite conversion of
      cytosines. RESULTS: A statistical model is developed which accounts for the
      distribution of DNA methylation patterns at any given locus. The model
      incorporates the effects of sequencing errors and spurious reads, and enables
      estimation of the true underlying distribution of methylation patterns.
      CONCLUSIONS: Calculation of the estimated distribution over methylation patterns
      is implemented in the R Bioconductor package MPFE. Source code and documentation
      of the package are also available for download at
      http://bioconductor.org/packages/3.0/bioc/html/MPFE.html .

PMID- 25943747
TI  - Metronomic oral vinorelbine as first-line treatment in elderly patients with
      advanced non-small cell lung cancer: results of a phase II trial (MOVE trial).
AB  - BACKGROUND: Metronomic oral vinorelbine could be a safe option for elderly
      patients with advanced non small cell lung cancer (NSCLC). Metronomic
      administration of chemotherapy leads to a cytostatic action shifting treatment
      target from cancer cell to tumor angiogenesis. METHODS: 43 chemotherapy naive
      elderly (>= 70 yrs) PS 0-2 patients with stage IIIB-IV NSCLC were prospectively
      recruited. Median age was 80 yrs (M/F 36/7) with predominantly squamous
      histology. PS distribution was 0-1(16)/2(27) with a median of 3 serious co-morbid
      illnesses. Study treatment consisted of oral vinorelbine 50mg three times weekly
      (Monday-Wednesday-Friday) continuously until disease progression, unacceptable
      toxicity or patient refusal. Primary endpoints were overall response rate (ORR),
      clinical benefit (CB--disease response plus disease stabilization >12 weeks) and
      safety. Health-related QoL (HRQoL) was also assessed with FACT-L V4 scoring
      questionnaire. We conducted an exploratory time-course analysis of VEGF and
      thrombospondin-1 (TSP1) serum levels in a subgroup of patients. RESULTS: Patients
      received a median of 5 (range 1-21) cycles with a total of 272 cycles delivered.
      ORR was 18.6% with 7 partial and 1 complete responses; 17/43 experienced stable
      disease lasting more than 12 weeks leading to an overall CB of 58.1%. Median time
      to progression was 5 (range 2-21) and median overall survival 9 (range 3-29)
      months. Treatment was well tolerated with rare serious toxicity. Regardless of
      severity main toxicities observed were anemia in 44%, fatigue in 32.4%, and
      diarrhoea 10.5%. FACT-L v4 scores did not significantly vary during treatment.
      Baseline VEGF levels were lower and showed a rapid increase during treatment in
      non-responders pts only while TSP1 levels did not change. CONCLUSIONS: Metronomic
      oral vinorelbine is safe in elderly patients with advanced NSCLC with an
      interesting activity mainly consisting in long-term disease stabilization coupled
      with an optimal patient compliance (Eudra-CT 2010-018762-23, AIFA OSS on 26
      February 2010).

PMID- 25943748
TI  - Sugar intake: lowering the bar.

PMID- 25943749
TI  - Reversible biological adaptations in obesity.

PMID- 25943750
TI  - Reversible biological adaptations in obesity - Authors' reply.

PMID- 25943751
TI  - Effects of RAS inhibitors on diabetic retinopathy.

PMID- 25943752
TI  - Cardiovascular disease risk in type 1 diabetes.

PMID- 25943753
TI  - Effects of RAS inhibitors on diabetic retinopathy - Authors' reply.

PMID- 25943754
TI  - Cardiovascular disease risk in type 1 diabetes - Authors' reply.

PMID- 25943756
TI  - Pleiotropic effects of type 2 diabetes management strategies on renal risk
      factors.
AB  - In parallel with the type 2 diabetes pandemic, diabetic kidney disease has become
      the leading cause of end-stage renal disease worldwide, and is associated with
      high cardiovascular morbidity and mortality. As established in landmark
      randomised trials and recommended in clinical guidelines, prevention and
      treatment of diabetic kidney disease focuses on control of the two main renal
      risk factors, hyperglycaemia and systemic hypertension. Treatment of systemic
      hypertension with angiotensin-converting enzyme inhibitors or angiotensin
      receptor blockers is advocated because these drugs seem to exert specific
      renoprotective effects beyond blood pressure lowering. Emerging evidence shows
      that obesity, glomerular hyperfiltration, albuminuria, and dyslipidaemia might
      also adversely affect the kidney in diabetes. Control of these risk factors could
      have additional benefits on renal outcome in patients with type 2 diabetes.
      However, despite multifactorial treatment approaches, residual risk for the
      development and progression of diabetic kidney disease in patients with type 2
      diabetes remains, and novel strategies or therapies to treat the disease are
      urgently needed. Several drugs used in the treatment of type 2 diabetes are
      associated with pleiotropic effects that could favourably or unfavourably change
      patients' renal risk profile. We review the risk factors and treatment of
      diabetic kidney disease, and describe the pleiotropic effects of widely used
      drugs in type 2 diabetes management on renal outcomes, with special emphasis on
      antihyperglycaemic drugs. 

PMID- 25943757
TI  - Non-proteinuric pathways in loss of renal function in patients with type 2
      diabetes.
AB  - Largely on the basis of data from patients with type 1 diabetes, the natural
      history of diabetic renal disease has been classified as a sequence of three
      stages: normoalbuminuria, microalbuminuria, and macroalbuminuria. Progressive
      decline of glomerular filtration rate (GFR) was thought to parallel the onset of
      macroalbuminuria (overt nephropathy), whereas glomerular hyperfiltration was
      deemed a hallmark of early disease. However, researchers have since shown that
      albuminuria is a continuum and that GFR can start to decline before progression
      to overt nephropathy. In addition to proteinuria, other risk factors might
      contribute to GFR deterioration including female sex, obesity, dyslipidaemia (in
      particular hypertriglyceridaemia), hypertension, and glomerular hyperfiltration,
      at least in a subgroup of patients. This phenomenon could explain why patients
      with type 2 diabetes can have renal insufficiency even before the onset of overt
      nephropathy, and might also suggest why the heterogeneous phenotype of type 2
      diabetic renal disease does not necessarily associate with typical histological
      lesions of diabetic renal disease, unlike in type 1 diabetic renal disease.
      Patients with renal insufficiency but without albuminuria are usually excluded
      from randomised clinical trials in overt nephropathy, thus optimum treatment for
      this group of patients is unknown. The wide inter-patient variability of the
      disease probably needs individually tailored intervention. 

PMID- 25943758
TI  - Effects of a fruit-vegetable dietary pattern on oxidative stress and genetic
      damage in coke oven workers: a cross-sectional study.
AB  - BACKGROUND: Coke oven workers (COWs) are exposed to high level of genotoxic
      chemicals that induce oxidative stress and genetic damage. The dietary intake of
      certain types of foods may reverse these effects. METHODS: We conducted a cross
      sectional study with 51 topside COWs, 79 other COWs, and 67 controls, to assess
      the effects of dietary patterns on oxidative stress and genetic damage. RESULTS:
      Compared to the controls, both topside and other COWs had significantly higher
      urinary 1-hydroxypyrene levels, serum oxidant levels [malondialdehyde, (MDA)],
      and genetic damage [micronucleus (MN) frequency & 8-oxo-2'-deoxyguanosine (8-OH
      dG)], but lower antioxidant levels [superoxide dismutase (SOD) and glutathione
      peroxidase, (GPx)]. The fruit-vegetable (FV) dietary pattern was positively
      correlated with serum SOD levels and negative correlated with serum MDA, MN
      frequency, and urinary 8-OH-dG. COWs with an FV patter in the highest quartile
      (Q4) had significantly increased antioxidant levels (SOD and GPx) and decreased
      oxidant levels (MDA) and genetic damage (MN frequency and 8-OH-dG) than those
      with an FV pattern in the lowest quartile (Q1). CONCLUSION: Compared to control
      subjects, COWs had increased oxidative stress and genetic damage. A FV dietary
      pattern may reverse oxidative stress and genetic damage in COWs.

PMID- 25943759
TI  - Effect of fipronil on energy metabolism in the perfused rat liver.
AB  - Fipronil is an insecticide used to control pests in animals and plants that can
      causes hepatotoxicity in animals and humans, and it is hepatically metabolized to
      fipronil sulfone by cytochrome P-450. The present study aimed to characterize the
      effects of fipronil (10-50MUM) on energy metabolism in isolated perfused rat
      livers. In fed animals, there was increased glucose and lactate release from
      glycogen catabolism, indicating the stimulation of glycogenolysis and glycolysis.
      In the livers of fasted animals, fipronil inhibited glucose and urea production
      from exogenous l-alanine, whereas ammonia and lactate production were increased.
      In addition, fipronil at 50MUM concentration inhibited the oxygen uptake and
      increased the cytosolic NADH/NAD+ ratio under glycolytic conditions. The
      metabolic alterations were found both in livers from normal or proadifen
      pretreated rats revealing that fipronil and its reactive metabolites contributed
      for the observed activity. The effects on oxygen uptake indicated that the
      possible mechanism of toxicity of fipronil involves impairment on mitochondrial
      respiratory activity, and therefore, interference with energy metabolism. The
      inhibitory effects on oxygen uptake observed at the highest concentration of
      50MUM was abolished by pretreatment of the rats with proadifen indicating that
      the metabolites of fipronil, including fipronil sulfone, acted predominantly as
      inhibitors of respiratory chain. The hepatoxicity of both the parent compound and
      its reactive metabolites was corroborated by the increase in the activity of
      lactate dehydrogenase in the effluent perfusate in livers from normal or
      proadifen-pretreated rats.

PMID- 25943760
TI  - Acrylamide increases dopamine levels by affecting dopamine transport and
      metabolism related genes in the striatal dopaminergic system.
AB  - Dopaminergic system dysfunction is proved to be a possible mechanism in
      acrylamide (ACR) -induced neurotoxicity. The neurotransmitter dopamine (DA) has
      an increasingly important role in the dopaminergic system. Thus, the goal of this
      study is to evaluate effects of ACR on dopamine and its metabolite levels,
      dopamine transport and metabolic gene expression in dopaminergic neurons. Male
      Sprague-Dawley (SD) rats were dosed orally with ACR at 0 (saline), 20, 30, and 40
      mg/kg/day for 20 days. Splayed hind limbs, reduced tail flick time and abnormal
      gait which preceded other neurologic parameters were observed in the above rats.
      ACR significantly increased dopamine levels, decreased 3,4-dihydroxyphenylacetic
      acid (DOPAC) and homovanilic acid (HVA) contents in an area dependent manner in
      rat striatum. Immunohistochemical staining of the striatum revealed that the
      number of tyrosine hydroxylase (TH) positive cells significantly increased, while
      monoamine oxidase (MAO) positive cells were drastically reduced, which was
      consistent with changes in their mRNA and protein expressions. In addition,
      dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2)
      expression levels were both down-regulated in the striatum. These results suggest
      that dopamine levels increase significantly in response to ACR, presumably due to
      changes in the dopamine transport and metabolism related genes expression in the
      striatal dopaminergic neurons.

PMID- 25943761
TI  - Cost-Effectiveness of Integrating Tobacco Cessation Into Post-Traumatic Stress
      Disorder Treatment.
AB  - INTRODUCTION: We examined the cost-effectiveness of smoking cessation integrated
      with treatment for post-traumatic stress disorder (PTSD). METHODS: Smoking
      veterans receiving care for PTSD (N = 943) were randomized to care integrated
      with smoking cessation versus referral to a smoking cessation clinic. Smoking
      cessation services, health care cost and utilization, quality of life, and
      biochemically-verified abstinence from cigarettes were assessed over 18-months of
      follow-up. Clinical outcomes were combined with literature on changes in smoking
      status and the effect of smoking on health care cost, mortality, and quality of
      life in a Markov model of cost-effectiveness over a lifetime horizon. We
      discounted cost and outcomes at 3% per year and report costs in 2010 US dollars.
      RESULTS: The mean of smoking cessation services cost was $1286 in those
      randomized to integrated care and $551 in those receiving standard care (P <
      .001). There were no significant differences in the cost of mental health
      services or other care. After 12 months, prolonged biochemically verified
      abstinence was observed in 8.9% of those randomized to integrated care and 4.5%
      of those randomized to standard care (P = .004). The model projected that
      Integrated Care added $836 in lifetime cost and generated 0.0259 quality adjusted
      life years (QALYs), an incremental cost-effectiveness ratio of $32 257 per QALY.
      It was 86.0% likely to be cost-effective compared to a threshold of $100
      000/QALY. CONCLUSIONS: Smoking cessation integrated with treatment for PTSD was
      cost-effective, within a broad confidence region, but less cost-effective than
      most other smoking cessation programs reported in the literature.

PMID- 25943763
TI  - Simultaneous And Extended Delivery Of Stavudine, Lamivudine And Nevirapine In
      Fixed Dose Combination Using Sandwiched Osmotic Tablets For Hiv Therapy.
AB  - Current HIV-therapy recommends combination of stavudine, lamivudine and
      nevirapine. Stavudine and lamivudine are administered as fixed combination while
      nevirapine as separate dosage form which often results in poor compliance and
      adherence to therapy by patients and therefore, there is a need to develop dosage
      forms that can overcome the problems of currently available dosage forms for
      treatment of HIV infection. The present study developed a single unit osmotic
      system for simultaneous and extended delivery of stavudine, lamivudine and
      nevirapine that can ensure patients compliance and adherence to HIV-therapy.
      Sandwich osmotic pump tablets (SOPTs) of stavudine, lamivudine and nevirapine in
      fixed dose combination were designed and evaluated for the effect of variables
      such as PEO (polymer), KCl (osmogen), and orifice diameter on the physicochemical
      characteristics and the release behavior of the drugs. A 24 h zero order release
      of stavudine, lamivudine and nevirapine from the formulations was observed and
      the release rate of the drugs was found to be affected by PEO, KCl, and orifice
      diameter. The in vitro release data of SOPT correlated with in vivo predictions
      by super - position method. The results of the study propose that a single unit
      osmotic system (SOPT) of stavudine, lamivudine and nevirapine is beneficial to
      overcome the disadvantages of currently available dosage forms for effective
      control of HIV infection. 

PMID- 25943762
TI  - Frequency of sarcopenia and associated factors among hospitalized elderly
      patients.
AB  - BACKGROUND: Sarcopenia is an important public health problem that affects mainly
      elders, and has negative consequences, such as disability and even death. Due to
      the lack of studies evaluating sarcopenia in elderly persons hospitalized in
      Brazil, the aim of the present study was to describe the frequency of sarcopenia
      and associated factors among elders in a hospital in the city of Salvador-Brazil.
      METHODS: This cross-sectional study included 110 hospitalized elderly patients in
      a multi-specialty hospital in Salvador-BA, Brazil. Inclusion criteria: were
      elders aged >=60 years between the first and fifth day of hospitalization; who
      were able to walk without external assistance; with medical permission to walk,
      and who did not take vasoactive and inotropic drugs. The diagnosis of sarcopenia
      was determined by combining the reduction in skeletal muscle mass with muscle
      weakness (women, <20 kg; men, <30 kg) and/or poor physical performance (gait
      speed <=0.8 m/s). To obtain reduced skeletal muscle mass, the skeletal muscle
      mass index <=6.37 kg/m(2) for women and <=8.90 kg/m(2) for men was used.
      Cognitive function, Charlson index, admission profile (clinical and surgical),
      smoking, falls suffered in the last year and physical inactivity prior to
      admission were also evaluated. The frequency of sarcopenia was described in
      percentages with their respective confidence intervals and logistic regression
      was performed for multivariate analysis of factors associated with sarcopenia.
      RESULTS: Among the 110 patients included, the frequency of sarcopenia was 21.8%,
      with 10.0% being of the severe type. There was a predominance of clinical profile
      (59.1%), such as heart disease (20.0%), pneumonia (13.6%) and skin infections
      (9.1%), with a Charlson index of 5.4 +/- 1.8. The factors associated with
      sarcopenia were age (OR = 1.14; 95% CI = 1.06 to 1.23), clinical profile on
      admission (OR = 5.15; 95% CI = 1.16-22.9) and smoking (OR = 7.8; 95% CI = 1.53
      39.9). CONCLUSIONS: The frequency of sarcopenia in elderly hospitalized patients
      was high (1 in 5 elderly) and anthropometric equation can be a viable and
      inexpensive alternative to screening and programming intervention in this
      population.

PMID- 25943764
TI  - Altering metabolic profiles of drugs by precision deuteration: reducing mechanism
      based inhibition of CYP2D6 by paroxetine.
AB  - Selective deuterium substitution as a means of ameliorating clinically relevant
      pharmacokinetic drug interactions is demonstrated in this study. Carbon-deuterium
      bonds are more stable than corresponding carbon-hydrogen bonds. Using a precision
      deuteration platform, the two hydrogen atoms at the methylenedioxy carbon of
      paroxetine were substituted with deuterium. The new chemical entity, CTP-347
      [(3S,4R)-3-((2,2-dideuterobenzo[d][1,3]dioxol-5-yloxy)methyl)-4-(4
      fluorophenyl)piperidine], demonstrated similar selectivity for the serotonin
      receptor, as well as similar neurotransmitter uptake inhibition in an in vitro
      rat synaptosome model, as unmodified paroxetine. However, human liver microsomes
      cleared CTP-347 faster than paroxetine as a result of decreased inactivation of
      CYP2D6. In phase 1 studies, CTP-347 was metabolized more rapidly in humans and
      exhibited a lower pharmacokinetic accumulation index than paroxetine. These
      alterations in the metabolism profile resulted in significantly reduced drug-drug
      interactions between CTP-347 and two other CYP2D6-metabolized drugs: tamoxifen
      (in vitro) and dextromethorphan (in humans). Our results show that precision
      deuteration can improve the metabolism profiles of existing pharmacotherapies
      without affecting their intrinsic pharmacologies. 

PMID- 25943765
TI  - Effects of acute, intermittent exercise in hypoxic environments on the release of
      cardiac troponin.
AB  - The purpose of this study was to examine the effects of acute, intermittent
      exercise performed in hypoxic environments on the release of cardiac troponin
      (cTn). Ten well-trained, male marathon runners (22.1 +/- 2.6 years, 64.0 +/- 4.9
      kg and 177.3 +/- 3.9 cm) completed three intermittent exercise protocols under
      normoxic (trial N) and hypoxic (trial AH and RH) conditions. In trial N, the
      fraction of inspiration oxygen (FIO2 ) was 21.0% and exercise intensity was 90%
      and 50% normoxic velocity of VO2max (vVO2max). In trial AH, FIO2 was 14.4%
      (simulated altitude of 3000 m) and exercise intensity was 90% and 50% normoxic
      vVO2max. In trial RH, FIO2 was 14.4% and exercise intensity was 90% and 50%
      hypoxic vVO2max. High-sensitivity cardiac troponin T (hs-cTnT) and cardiac
      troponin I (cTnI) were measured pre- and 0, 2, 4, and 24 h post-exercise. Hs-cTnT
      was elevated in all three trials, peaking at 2 to 4 h and returning to the
      baseline 24 h post-exercise. CTnI increased in trial AH, peaking at 2 to 4 h and
      returning below the detection limit 24 h post-exercise. It is concluded that the
      stimulus of hypoxia did not in and of itself induce more cTn to be released, but
      exercise intensity could affect this response in hypoxic environments.

PMID- 25943766
TI  - Representation of Naturalistic Image Structure in the Primate Visual Cortex.
AB  - The perception of complex visual patterns emerges from neuronal activity in a
      cascade of areas in the primate cerebral cortex. We have probed the early stages
      of this cascade with "naturalistic" texture stimuli designed to capture key
      statistical features of natural images. Humans can recognize and classify these
      synthetic images and are insensitive to distortions that do not alter the local
      values of these statistics. The responses of neurons in the primary visual
      cortex, V1, are relatively insensitive to the statistical information in these
      textures. However, in the area immediately downstream, V2, cells respond more
      vigorously to these stimuli than to matched control stimuli. Humans show blood
      oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI responses
      in V1 and V2) that are consistent with the neuronal measurements in macaque.
      These fMRI measurements, as well as neurophysiological work by others, show that
      true natural scenes become a more prominent driving feature of cortex downstream
      from V2. These results suggest a framework for thinking about how information
      about elementary visual features is transformed into the specific representations
      of scenes and objects found in areas higher in the visual pathway. 

PMID- 25943767
TI  - Causal Model Comparison Shows That Human Representation Learning Is Not Bayesian.
AB  - How do we learn what features of our multidimensional environment are relevant in
      a given task? To study the computational process underlying this type of
      "representation learning," we propose a novel method of causal model comparison.
      Participants played a probabilistic learning task that required them to identify
      one relevant feature among several irrelevant ones. To compare between two models
      of this learning process, we ran each model alongside the participant during task
      performance, making predictions regarding the values underlying the participant's
      choices in real time. To test the validity of each model's predictions, we used
      the predicted values to try to perturb the participant's learning process: We
      crafted stimuli to either facilitate or hinder comparison between the most highly
      valued features. A model whose predictions coincide with the learned values in
      the participant's mind is expected to be effective in perturbing learning in this
      way, whereas a model whose predictions stray from the true learning process
      should not. Indeed, we show that in our task a reinforcement-learning model could
      help or hurt participants' learning, whereas a Bayesian ideal observer model
      could not. Beyond informing us about the notably suboptimal (but computationally
      more tractable) substrates of human representation learning, our manipulation
      suggests a sensitive method for model comparison, which allows us to change the
      course of people's learning in real time. 

PMID- 25943768
TI  - Early Language Learning and the Social Brain.
AB  - Explaining how every typically developing child acquires language is one of the
      grand challenges of cognitive neuroscience. Historically, language learning
      provoked classic debates about the contributions of innately specialized as
      opposed to general learning mechanisms. Now, new data are being brought to bear
      from studies that employ magnetoencephalograph (MEG), electroencephalograph
      (EEG), magnetic resonance imaging (MRI), and diffusion tensor imaging (DTI)
      studies on young children. These studies examine the patterns of association
      between brain and behavioral measures. The resulting data offer both expected
      results and surprises that are altering theory. As we uncover what it means to be
      human through the lens of young children, and their ability to speak, what we
      learn will not only inform theories of human development, but also lead to the
      discovery of neural biomarkers, early in life, that indicate risk for language
      impairment and allow early intervention for children with developmental
      disabilities involving language. 

PMID- 25943769
TI  - Dopaminergic Dynamics Contributing to Social Behavior.
AB  - Social interaction is a complex behavior that is essential for the survival of
      many species, and it is impaired in a broad range of neuropsychiatric disorders.
      Several cortical and subcortical brain regions have been implicated in a variety
      of sociosexual behaviors, with pharmacological studies pointing to a key role of
      the neurotransmitter dopamine. However, little is understood about the real-time
      circuit dynamics causally underlying social interaction. Here, we consider
      current knowledge on the role of brain reward circuitry in same-sex social
      behavior and describe findings from new methods for probing how this circuitry
      governs social motivation in health and disease. 

PMID- 25943770
TI  - The Macaque Face Patch System: A Window into Object Representation.
AB  - The macaque brain contains a set of regions that show stronger fMRI activation to
      faces than other classes of object. This "face patch system" has provided a
      unique opportunity to gain insight into the organizing principles of IT cortex
      and to dissect the neural mechanisms underlying form perception, because the
      system is specialized to process one class of complex forms, and because its
      computational components are spatially segregated. Over the past 5 years, we have
      set out to exploit this system to clarify the nature of object representation in
      the brain through a multilevel approach combining electrophysiology, anatomy, and
      behavior. These experiments reveal (1) a remarkably precise connectivity of face
      patches to each other, (2) a functional hierarchy for representation of view
      invariant identity comprising at least three distinct stages along the face patch
      system, and (3) the computational mechanisms used by cells in face patches to
      detect and recognize faces, including measurement of diagnostic local contrast
      features for detection and measurement of face feature values for recognition. 

PMID- 25943771
TI  - Visual profile of students in integrated schools in Malawi.
AB  - BACKGROUND: Blindness and visual impairment are very common in African countries
      and are often loosely linked to inadequate resources. We designed this study to
      assess clinical visual and ocular characteristics of children in three integrated
      schools in Malawi, so that students needing low vision services or those with
      correctable refractive error will be identified. METHODS: We included 95
      students, who underwent a detailed optometric examination. The assessment
      included distance visual acuity measurement in logMAR notation, near visual
      acuity, oculo-motor assessment, pupillary assessment and anterior as well as
      posterior segment evaluation. Non-cycloplegic refraction was done in all the
      participants. RESULTS: Mean age of students was 13.84 +/-4.61 years. Almost 90
      per cent of students had presenting visual acuity worse than logMAR 0.54. Visual
      acuity improved significantly after refractive correction by more than two logMAR
      lines in 31.8 per cent (p < 0.0001). Refractive error was very common (36.5 per
      cent) and the most common causes of visual impairment were lenticular (21.2 per
      cent), corneal (20.0 per cent) and albinism (15.3 per cent). One-tenth (10.5 per
      cent) of the students were wrongly enrolled in the schools, even though they did
      not have visual impairment. The compliance to spectacles wear was very poor (37
      per cent). An adequate refractive correction improved visual acuity in more than
      a third (36.5 per cent) of the students. Students benefited from spectacle
      magnifiers (18.8 per cent), handheld magnifiers (4.7 per cent) and telescopes
      (5.9 per cent). Mobility canes were advised for 36.5 per cent of the students.
      CONCLUSION: Nine out of ten students in three integrated schools in Malawi had
      visual impairment and 41 per cent had low vision. Inappropriate placement in the
      integrated schools and poor spectacle compliance are very common. Well accepted
      optical and non-optical devices could improve visual performance in visually
      disabled children, for which public awareness and parental education is
      important.

PMID- 25943772
TI  - Influence of the aortic valve leaflets on the fluid-dynamics in aorta in presence
      of a normally functioning bicuspid valve.
AB  - In this work, we consider the blood fluid-dynamics in the ascending aorta in
      presence of a normally functioning bicuspid aortic valve (BAV). In particular, we
      perform an unsteady finite element study in real geometries with physiological
      velocity boundary conditions at the inlet to assess the effect of the inclusion
      of the leaflets on the fluid-dynamic abnormalities characterizing BAV cases. To
      this aim, we perform a comparison in two geometries (a dilated and a non-dilated
      ones) among three scenarios which are built up for each geometry: BAV without
      leaflets, BAV with leaflets, and tricuspid case with leaflets. For each case, we
      compute four indices quantifying flow asymmetry, reversal flows, helical
      patterns, and wall shear stresses. Our results show that the inclusion of the
      leaflets increases the fluid-dynamics abnormalities, especially for the non
      dilated configuration, which presents a greater increment of the indices. In
      particular, we observe that the values of the time-averaged wall shear stress and
      of the systolic jet asymmetry increase by approximatively 100 and 40%,
      respectively, when considering the leaflets.

PMID- 25943773
TI  - The influence of Helicobacter pylori eradication on the expression and
      methylation status of the FHIT gene in non-cancerous gastric mucosa of dyspeptic
      patients.
AB  - OBJECTIVE: To investigate the effect of Helicobacter pylori (H. pylori)
      eradication on the expression level of the FHIT gene and its methylation status
      in the gastric mucosa of dyspeptic patients with or without a family history of
      gastric cancer (FHGC). METHODS: In all, 31 patients with H. pylori infection
      including 13 with FHGC were enrolled in the study. The effectiveness of H. pylori
      eradication were confirmed by UBT, RUT and multiplex PCR (the presence of
      selected H. pylori strains) for biopsy samples from the antrum and corpus.
      Histopathological assessment was also performed. The expression of FHIT mRNA was
      determined by quantitative reverse transcription-polymerase chain reaction and
      the methylation status of the FHIT promoter was assessed by methylation-specific
      polymerase chain reaction. RESULTS: After H. pylori eradication, the improvement
      of inflammation from superficial gastritis to normal mucosa (G -> N) was observed
      in 39% of the patients without FHGC and in 54% of those with FHGC. FHIT mRNA
      expression was increased in patients without FHGC after H. pylori eradication (P
      < 0.05), while there was no statistically significant change in gene methylation
      status after H. pylori eradication (P > 0.05). For the samples from those with
      FHGC, the FHIT mRNA expression was not significantly changed and the methylation
      status fluctuated evenly. CONCLUSIONS: H. pylori eradication results in the
      improvement of gastric mucosal inflammation and histopathological non-atrophic
      changes. The FHIT gene expression is increased in patients without FHGC, which
      may contribute to the prevention of GC development.

PMID- 25943774
TI  - Highly Regiosymmetric Homopolymer Based on Dioxythiophene for Realizing Water
      Processable Blue-to-Transmissive Electrochrome.
AB  - A highly regiosymmetric homopolymer based on a diethyl malonate derivatized 3,4
      propylenedioxythiophene (ProDOT) monomer was synthesized through FeCl3 oxidative
      polymerization and postpolymerization functionalization to realize a water
      processable blue-to-transmissive switching electrochromic polymer (WPECP-blue).
      As an electrochromic material, the polymer has a high electrochromic contrast
      DeltaTmax=56% at 580 nm and a relatively fast switching speed t95=1.8 s, and
      shows only contrast loss of 11% (from 56% to 45%) at square wave potential step
      of 5 s over 11,000 switching cycles, making it a desirable candidate for
      electrochromic applications such as windows and displays.

PMID- 25943775
TI  - Identification of the salmonid IL-17A/F1a/b, IL-17A/F2b, IL-17A/F3 and IL-17N
      genes and analysis of their expression following in vitro stimulation and
      infection.
AB  - This study identifies four new IL-17A/F isoforms in salmonids, as well as IL-17N.
      IL-17A/F1 and IL-17A/F2 are each represented by two paralogues, with a predicted
      pseudogene of IL-17N also apparent in the salmonid genome. Analysis of the
      sequences and genes of the known IL-17A/F and IL-17N molecules suggests that IL
      17N is a member within the IL-17A/F subfamily. Analysis of factors that modulated
      the expression of these genes showed that PHA and PMA were good inducers of
      salmon IL-17A/F1a and IL-17A/F2a, with rIL-21 a potent stimulator of IL-17A/F1a
      and IL-17A/F3. The potential involvement of these isoforms during responses post
      vaccination and infection was also studied. In unvaccinated control fish,
      Yersinia ruckeri infection resulted in a marked up-regulation of IL-17A/F1a and
      IL-17N in the spleen and head kidney and IL-17A/F2a and IL-17A/F3 in the spleen.
      In the vaccinated fish, only one significant increase was seen relative to
      control fish, of IL-17A/F2a in the gills, whether the fish were challenged with
      Y. ruckeri or given the saline placebo. It was also apparent in the gills and
      head kidney that the level of IL-17A/F1b remained elevated in the Y. ruckeri
      challenged fish at a time when it had decreased in saline-injected fish. The
      relative importance of these isoforms for disease resistance remains to be
      determined. 

PMID- 25943776
TI  - Clinical and parental age characteristics of rare copy number variant burden in
      patients with schizophrenia.
AB  - Copy number variant (CNV) burden, especially for rare deletions, has been
      associated with risk for schizophrenia as well as phenotypic differences within
      cognitive and neuroimaging domains. The current study investigated clinical and
      parental age characteristics of rare CNV burden in patients with schizophrenia.
      Clinical data was collected for 629 patients with schizophrenia who formed part
      of a genomewide association study, which included CNV data. Parental age was
      available for 368 patients. Correlations were calculated between burden scores
      and positive, negative, and mood symptoms from the Lifetime Diagnostic Psychosis
      Scale as well as age at onset. Patients were grouped according to number of rare
      deletions, duplications, or total CNVs and MANOVAs used to investigate
      differences in clinical and parental age characteristics. Patients with the least
      number of CNVs had older fathers and larger parental age difference. Patients
      with no deletions had older mothers and those with five or more deletions had
      younger mothers. Total deletion, duplication, and CNV burden, as measured by
      number of base pairs, were not associated with clinical or parental age
      differences although total rare duplication burden had a negative correlation
      with positive symptoms that did not survive correction for multiple testing.
      Likewise, a positive correlation between age at onset and total CNV burden did
      not survive correction. Rare CNVs are associated with differences in parental age
      in patients with schizophrenia. No robust clinical differences were identified.
      However, duplication burden may have a small protective effect against positive
      symptoms and age at onset may be influenced by total CNV burden. No clinical
      differences were associated with deletion burden measures.

PMID- 25943778
TI  - Transcriptome analysis of predator- and prey-induced phenotypic plasticity in the
      Hokkaido salamander (Hynobius retardatus).
AB  - Predator- and prey-induced phenotypic plasticity is widely observed among
      amphibian species. Although ecological factors inducing diverse phenotypic
      responses have been extensively characterized, we know little about the molecular
      bases of variation in phenotypic plasticity. Larvae of the Hokkaido salamander,
      Hynobius retardatus, exhibit two distinct morphs: the presence of their prey,
      Rana pirica tadpoles, induces a broad-headed attack morph, and the presence of
      predatory dragonfly nymphs (Aeshna nigroflava) induces a defence morph with
      enlarged external gills and a high tail. To compare the genes involved in
      predator- and prey-induced phenotypic plasticity, we carried out a de novo
      transcriptome analysis of Hokkaido salamander larvae exposed to either prey or
      predator individuals. First, we found that the number of genes involved in the
      expression of the defence morph was approximately five times the number involved
      in the expression of the attack morph. This result is consistent with the fact
      that the predator-induced plasticity involves more drastic morphological changes
      than the prey-induced plasticity. Second, we found that particular sets of genes
      were upregulated during the induction of both the attack and defence morphs, but
      others were specific to the expression of one or the other morph. Because both
      shared and unique molecular mechanisms were used in the expression of each morph,
      the evolution of a new plastic phenotype might involve both the co-option of pre
      existing molecular mechanisms and the acquisition of novel regulatory mechanisms.

PMID- 25943777
TI  - Granulosa Cell-Specific Brca1 Loss Alone or Combined with Trp53
      Haploinsufficiency and Transgenic FSH Expression Fails to Induce Ovarian Tumors.
AB  - BRCA1 mutations are associated with ovarian cancer. Previous studies reported
      that murine granulosa cell (GC) Brca1 loss caused ovarian-uterine tumors
      resembling serous cystadenomas, but the pathogenesis of these tumors may have
      been confounded by ectopic Brca1 expression and altered estrous cycling. We have
      used Tg.AMH.Cre conferring proven ovarian and GC-specific Cre activity to
      selectively target Brca1 disruption, denoted Brca1(GC-/-). Furthermore, ovary
      specific Brca1(GC-/-) was combined with global Trp53 haploinsufficiency (Trp53(+/
      )) and transgenic follicle-stimulating hormone (Tg.FSH) overexpression as a multi
      hit strategy to investigate additional genetic and hormonal ovarian tumorigenesis
      mechanisms. However, 12-month-old Brca1(GC-/-) mice had no detectable ovarian or
      uterine tumors. Brca1(GC-/-) mice had significantly increased ovary weights,
      follicles exhibiting more pyknotic granulosa cells, and fewer corpora lutea with
      regular estrous cycling compared to controls. Isolated Brca1(GC-/-) mutation
      lengthened the estrous cycle and proestrus stage; however, ovarian cystadenomas
      were not observed, even when Brca1(GC-/-) was combined with Trp53(+/-) and
      overexpressed Tg.FSH. Our Brca1(GC-/-) models reveal that specific intra
      follicular Brca1 loss alone, or combined with cancer-promoting genetic (Trp53
      loss) and endocrine (high serum FSH) changes, was not sufficient to cause ovarian
      tumors. Our findings show that the ovary is remarkably resistant to oncogenesis,
      and support the emerging view of an extragonadal, multi-hit origin for ovarian
      tumorigenesis.

PMID- 25943779
TI  - In memory of Professor John H. Laragh.

PMID- 25943781
TI  - Quality of life, social support and cognitive impairment in heart failure
      patients without diagnosed dementia.
AB  - Improving health-related quality of life (HRQL) is an important goal for heart
      failure (HF) patients, and understanding the factors that influence HRQL is
      essential to this process. We investigated the influence of social support and
      cognitive impairment on HRQL in community dwelling HF patients (n = 104) without
      diagnosed dementia. Patients were aged mean 80.93 years (SD 11.01) and were
      classified as New York Heart Association Class 1/II (45%) or III/IV (53%). Age,
      social support and cognition had important independent effects. Younger people
      had the most negative effects of HF in all areas of HRQL: emotional (B = -0.32),
      physical (B = -0.44) and overall (B = -1). Well-supported patients (general
      social support) had the least negative effect from HF on HRQL: emotional domain
      (B = -4.62) and overall (B = -11.72). Patients with normal cognition had more
      negative impact of HF on HRQL: physical domain (B = 5.51) and overall HRQL (B =
      10.42). A clearer understanding of the relationships between age, social support
      and cognition and the effect on the impact of HF on HRQL is needed before
      interventions can be appropriately developed. 

PMID- 25943782
TI  - Appendiceal mucocele: the importance of getting a preoperative diagnosis.

PMID- 25943780
TI  - Generation of cardiac progenitor cells through epicardial to mesenchymal
      transition.
AB  - The epithelial to mesenchymal transition (EMT) is a biological process that
      drives the formation of cells involved both in tissue repair and in pathological
      conditions, including tissue fibrosis and tumor metastasis by providing cancer
      cells with stem cell properties. Recent findings suggest that EMT is reactivated
      in the heart following ischemic injury. Specifically, epicardial EMT might be
      involved in the formation of cardiac progenitor cells (CPCs) that can
      differentiate into endothelial cells, smooth muscle cells, and, possibly,
      cardiomyocytes. The identification of mechanisms and signaling pathways governing
      EMT-derived CPC generation and differentiation may contribute to the development
      of a more efficient regenerative approach for adult heart repair. Here, we
      summarize key literature in the field. 

PMID- 25943783
TI  - Adenoid cystic carcinoma of the head and neck--An update.
AB  - This article provides an update on the current understanding of adenoid cystic
      carcinoma of the head and neck, including a review of its epidemiology, clinical
      behavior, pathology, molecular biology, diagnostic workup, treatment and
      prognosis. Adenoid cystic carcinoma is an uncommon salivary gland tumor that may
      arise in a wide variety of anatomical sites in the head and neck, often with an
      advanced stage at diagnosis. The clinical course is characterized by very late
      recurrences; consequently, clinical follow-up should extend at least >15 years.
      The optimal treatment is generally considered to be surgery with postoperative
      radiotherapy to optimize local disease control. Much effort has been invested
      into understanding the tumor's molecular biological processes, aiming to identify
      patients at high risk of recurrence, in hopes that they could benefit from other,
      still unproven treatment modalities such as chemotherapy or biological therapy.

PMID- 25943784
TI  - Triangular prism-shaped beta-peptoid helices as unique biomimetic scaffolds.
AB  - beta-Peptoids are peptidomimetics based on N-alkylated beta-aminopropionic acid
      residues (or N-alkyl-beta-alanines). This type of peptide mimic has previously
      been incorporated in biologically active ligands and has been hypothesized to be
      able to exhibit foldamer properties. Here we show, for the first time, that beta
      peptoids can be tuned to fold into stable helical structures. We provide high
      resolution X-ray crystal structures of homomeric beta-peptoid hexamers, which
      reveal right-handed helical conformations with exactly three residues per turn
      and a helical pitch of 9.6-9.8 A between turns. The presence of folded
      conformations in solution is supported by circular dichroism spectroscopy showing
      length- and solvent dependency, and molecular dynamics simulations provide
      further support for a stabilized helical secondary structure in organic solvent.
      We thus outline a framework for future design of novel biomimetics that display
      functional groups with high accuracy in three dimensions, which has potential for
      development of new functional materials. 

PMID- 25943785
TI  - Molecular and immunological characterization of three strains of Anaplasma
      marginale grown in cultured tick cells.
AB  - Anaplasma marginale is an economically important tick-borne pathogen of cattle
      that causes bovine anaplasmosis. A wide range of geographic strains of A.
      marginale have been isolated from cattle, several of which have been
      characterized using genomics and proteomics. While many of these strains have
      been propagated in tick lines, comparative analyses after propagation in tick
      cells have not been reported. The overall purpose of this research therefore was
      to compare the degree of conservation of selected genes after propagation in tick
      cell culture among A. marginale strains from the U.S. (the Virginia strain) and
      Brazil (UFMG1 and UFMG2 strains). The genes studied herein included those which
      encode the proteins HSP70 and SODB involved in heat shock and stress responses,
      respectively, and two genes that encode major surface proteins MSP4 and MSP5.
      Strain identities were first confirmed by sequencing the tandem repeats of the
      msp1a gene which encodes for the adhesin, MSP1a. The results of these studies
      demonstrated that the genes encoding for both stress response and heat shock
      proteins were highly conserved among the three A. marginale strains. Antibodies
      specific for MSP4, MSP5, SODB and HSP70 proteins were used to further
      characterize the A. marginale strains, and they reacted with all of these strains
      propagated in tick cell culture, providing further evidence for antigenic
      conservation. Although antigenic differences were not found among the three A.
      marginale strains, multi-locus sequence analysis (MLSA) performed with nucleotide
      sequences of these genes demonstrated that the A. marginale Brazilian and U.S.
      strains fall in different clades. These results showed that phylogenetically
      distant strains of A. marginale are antigenically conserved, even after several
      in vitro passages, supporting the use of some of the above conserved proteins as
      candidates for universal vaccines. 

PMID- 25943786
TI  - Evidence of an epigenetic origin for high-risk 1q21 copy number aberrations in
      multiple myeloma.
AB  - Multiple myeloma is a B-cell malignancy stratified in part by cytogenetic
      abnormalities, including the high-risk copy number aberrations (CNAs) of +1q21
      and 17p(-). To investigate the relationship between 1q21 CNAs and DNA
      hypomethylation of the 1q12 pericentromeric heterochromatin, we treated in vitro
      peripheral blood cultures of 5 patients with balanced constitutional
      rearrangements of 1q12 and 5 controls with the hypomethylating agent 5
      azacytidine. Using G-banding, fluorescence in situ hybridization, and spectral
      karyotyping, we identified structural aberrations and copy number gains of 1q21
      in the treated cells similar to those found in patients with cytogenetically
      defined high-risk disease. Aberrations included 1q12 triradials, amplifications
      of regions juxtaposed to 1q12, and jumping translocations 1q12. Strikingly, all 5
      patients with constitutional 1q12 rearrangements showed amplifications on the
      derivative chromosomes distal to the inverted or translocated 1q12 region,
      including MYCN in 1 case. At the same time, no amplification of the 1q21 region
      was found when the 1q12 region was inverted or absent. These findings provide
      evidence that the hypomethylation of the 1q12 region can potentially amplify any
      genomic region juxtaposed to it and mimic CNAs found in the bone marrow of
      patients with high-risk disease. 

PMID- 25943787
TI  - Dengue virus binding and replication by platelets.
AB  - Dengue virus (DENV) infection causes ~200 million cases of severe flulike illness
      annually, escalating to life-threatening hemorrhagic fever or shock syndrome in
      ~500,000. Although thrombocytopenia is typical of both mild and severe diseases,
      the mechanism triggering platelet reduction is incompletely understood. As a
      probable initiating event, direct purified DENV-platelet binding was followed in
      the current study by quantitative reverse transcription-polymerase chain reaction
      and confirmed antigenically. Approximately 800 viruses specifically bound per
      platelet at 37 degrees C. Fewer sites were observed at 25 degrees C, the blood
      bank storage temperature (~350 sites), or 4 degrees C, known to attenuate virus
      cell entry (~200 sites). Dendritic cell-specific intercellular adhesion molecule
      3-grabbing nonintegrin (DC-SIGN) and heparan sulfate proteoglycan were implicated
      as coreceptors because only the combination of anti-DC-SIGN and low-molecular
      weight heparin prevented binding. Interestingly, at 37 degrees C and 25 degrees
      C, platelets replicated the positive sense single-stranded RNA genome of DENV by
      up to ~4-fold over 7 days. Further time course experiments demonstrated
      production of viral NS1 protein, which is known to be highly antigenic in patient
      serum. The infectivity of DENV intrinsically decayed in vitro, which was
      moderated by platelet-mediated generation of viable progeny. This was shown using
      a transcription inhibitor and confirmed by freeze-denatured platelets being
      incapable of replicating the DENV genome. For the first time, these data
      demonstrate that platelets directly bind DENV saturably and produce infectious
      virus. Thus, expression of antigen encoded by DENV is a novel consideration in
      the pathogen-induced thrombocytopenia mechanism. These results furthermore draw
      attention to the possibility that platelets may produce permissive RNA viruses in
      addition to DENV.

PMID- 25943788
TI  - Occupational exposures and risk of dementia-related mortality in the prospective
      Netherlands Cohort Study.
AB  - BACKGROUND: Occupational exposures may be associated with non-vascular dementia.
      METHODS: We analyzed the effects of occupational exposures to solvents,
      pesticides, metals, extremely low frequency magnetic fields (ELF-MF), electrical
      shocks, and diesel motor exhaust on non-vascular dementia related mortality in
      the Netherlands Cohort Study (NLCS). Exposures were assigned using job-exposure
      matrices. After 17.3 years of follow-up, 682 male and 870 female cases were
      available. Analyses were performed using Cox regression. RESULTS: Occupational
      exposure to metals, chlorinated solvents and ELF-MF showed positive associations
      with non-vascular dementia among men, which seemed driven by metals (hazard ratio
      ever high vs. background exposure: 1.35 [0.98-1.86]). Pesticide exposure showed
      statistically significant, inverse associations with non-vascular dementia among
      men. We found no associations for shocks, aromatic solvents, and diesel motor
      exhaust. CONCLUSIONS: Consistent positive associations were found between
      occupational exposure to metals and non-vascular dementia. The finding on
      pesticides is not supported in the overall literature.

PMID- 25943789
TI  - Optimization of surface-immobilized extracellular matrices for the proliferation
      of neural progenitor cells derived from induced pluripotent stem cells.
AB  - Neural progenitor cells derived from induced pluripotent stem cells have been
      considered as a potential source for cell-transplantation therapy of central
      nervous disorders. However, efficient methods to expand neural progenitor cells
      are further required for their clinical applications. In this study, a protein
      array was fabricated with nine extracellular matrices and used to screen
      substrates suitable for the expansion of neural progenitor cells derived from
      mouse induced pluripotent stem cells. The results showed that neural progenitor
      cells efficiently proliferated on substrates with immobilized laminin-1, laminin
      5, or Matrigel. Based on this result, further attempts were made to develop
      clinically compliant substrates with immobilized polypeptides that mimic laminin
      1, one of the most effective extracellular matrices as identified in the array
      based screening. We used here recombinant DNA technology to prepare polypeptide
      containing the globular domain 3 of laminin-1 and immobilized it onto glass-based
      substrates. Our results showed that neural progenitor cells selectively
      proliferated on substrate with the immobilized polypeptide while maintaining
      their differentiated state.

PMID- 25943790
TI  - Results of sequential chemoradiotherapy for intracranial germinoma.
AB  - PURPOSE: To evaluate the efficacy of sequential chemoradiotherapy (CRT) for
      intracranial germinoma by long-term follow-up. MATERIALS AND METHODS: We
      retrospectively evaluated 23 consecutive intracranial germinoma patients without
      spinal dissemination, who had been treated by sequential CRT. All patients except
      for one were biopsied or surgically resected before treatment and all patients
      received both cranial and spinal magnetic resonance imaging. Three cycles of
      induction chemotherapy composed of etoposide and platinum agents were
      administered. The prescription of radiotherapy was 24 Gy per 12 fractions. No
      patients received spinal irradiation. RESULTS: All patients accomplished CRT and
      achieved complete remission. No severe acute and late toxicities were observed.
      Median follow-up time was 11.8 years. The 5- and 10-year overall survival rates
      were 100 and 100 %, and relapse-free survival rates were 96 and 89 %,
      respectively. Three patients developed intracranial recurrence and all of them
      were successfully salvaged by additional CRT. All patients were alive without
      disease at final follow-up. CONCLUSION: Treatment of 24 Gy of sequential CRT for
      intracranial germinoma might be promising as an alternative to radiotherapy
      alone. Spinal irradiation may not be necessary for patients who had no spinal
      dissemination and who were treated with CRT.

PMID- 25943791
TI  - Non-contact acoustic capture of microparticles from small plasma volumes.
AB  - Microparticles (MP) are small (100-1000 nm) membrane vesicles shed by cells as a
      response to activation, stress or apoptosis. Platelet-derived MP (PMP) has been
      shown to reflect the pathophysiological processes of a range of cardiovascular
      diseases and there is a potential clinical value in using PMPs as biomarkers, as
      well as a need to better understand the biology of these vesicles. The current
      method for isolating MP depends on differential centrifugation steps, which
      require relatively large sample volumes and have been shown to compromise the
      integrity and composition of the MP population. We present a novel method for
      rapid, non-contact capture of PMP in minute sample volumes based on a microscale
      acoustic standing wave technology. Capture of PMPs from plasma is shown by
      scanning electron microscopy and flow cytometry. Furthermore, the system is
      characterized with regards to plasma sample concentration and flow rate. Finally,
      the technique is compared to a standard differential centrifugation protocol
      using samples from both healthy controls and ST-elevation myocardial infarction
      (STEMI) patient samples. The acoustic system is shown to offer a quick and
      automated setup for extracting microparticles from small sample volumes with
      higher recovery than a standard differential centrifugation protocol. 

PMID- 25943792
TI  - Adverse Outcome Pathways can drive non-animal approaches for safety assessment.
AB  - Adverse Outcome Pathways (AOPs) provide an opportunity to develop new and more
      accurate safety assessment processes for drugs and other chemicals, and may
      ultimately play an important role in regulatory decision making. Not only can the
      development and application of AOPs pave the way for the development of improved
      evidence-based approaches for hazard and risk assessment, there is also the
      promise of a significant impact on animal welfare, with a reduced reliance on
      animal-based methods. The establishment of a useable and coherent knowledge
      framework under which AOPs will be developed and applied has been a first
      critical step towards realizing this opportunity. This article explores how the
      development of AOPs under this framework, and their application in practice,
      could benefit the science and practice of safety assessment, while in parallel
      stimulating a move away from traditional methods towards an increased acceptance
      of non-animal approaches. We discuss here the key areas where current, and future
      initiatives should be focused to enable the translation of AOPs into routine
      chemical safety assessment, and lasting 3Rs benefits.

PMID- 25943793
TI  - The proportion of genes in a functional category is linked to mass-specific
      metabolic rate and lifespan.
AB  - Metabolic rate and lifespan are important biological parameters that are studied
      in a wide range of research fields. They are known to correlate with body mass,
      but their association with gene (protein) functions is poorly understood. In this
      study, we collected data on the metabolic rate and lifespan of various organisms
      and investigated the relationship of these parameters with their genomes. We
      showed that the proportion of genes in a functional category, but not genome
      size, was correlated with mass-specific metabolic rate and maximal lifespan. In
      particular, the proportion of genes in oxic reactions (which occur in the
      presence of oxygen) was significantly associated with these two biological
      parameters. Additionally, we found that temperature, taxonomy, and mode-of-life
      traits had little effect on the observed associations. Our findings emphasize the
      importance of considering the biological functions of genes when investigating
      the relationships between genome, metabolic rate, and lifespan. Moreover, this
      provides further insights into these relationships, and may be useful for
      estimating metabolic rate and lifespan in individuals and the ecosystem using a
      combination of body mass measurements and genomic data. 

PMID- 25943794
TI  - Imaging learned fear circuitry in awake mice using fMRI.
AB  - Functional magnetic resonance imaging (fMRI) of learned behaviour in 'awake
      rodents' provides the opportunity for translational preclinical studies into the
      influence of pharmacological and genetic manipulations on brain function. fMRI
      has recently been employed to investigate learned behaviour in awake rats. Here,
      this methodology is translated to mice, so that future fMRI studies may exploit
      the vast number of genetically modified mouse lines that are available. One group
      of mice was conditioned to associate a flashing light (conditioned stimulus, CS)
      with foot shock (PG; paired group), and another group of mice received foot shock
      and flashing light explicitly unpaired (UG; unpaired group). The blood oxygen
      level-dependent signal (proxy for neuronal activation) in response to the CS was
      measured 24 h later in awake mice from the PG and UG using fMRI. The amygdala,
      implicated in fear processing, was activated to a greater degree in the PG than
      in the UG in response to the CS. Additionally, the nucleus accumbens was
      activated in the UG in response to the CS. Because the CS signalled an absence of
      foot shock in the UG, it is possible that this region is involved in processing
      the safety aspect of the CS. To conclude, the first use of fMRI to visualise
      brain activation in awake mice that are completing a learned emotional task is
      reported. This work paves the way for future preclinical fMRI studies to
      investigate genetic and environmental influences on brain function in transgenic
      mouse models of disease and aging.

PMID- 25943796
TI  - Vaccines: a step change in malaria prevention?

PMID- 25943795
TI  - [Preventive health care and health promotion: Which models for supporting the
      evolution of clinical practice in primary health care?].
AB  - OBJECTIVES: Published operating models about preventive health care and health
      promotion in primary care were sought with the aim of (1) compiling a functional
      inventory; and (2) to formulate working hypotheses for the improvement of
      clinical practice towards more efficiency and more equity. METHODS: Narrative
      literature review, using keywords related to the various prevention classes,
      health promotion, primary care, practice models and health care delivery. The
      diversity of models led to a multi-criteria analysis. RESULTS: Twelve models were
      selected. Their characteristics were unevenly distributed. The models, whose
      authors announce that they apply to prevention, mainly describe approaches that
      focus on individuals within physician-patient relationship, and take into account
      practice organization. Some socio-ecological and systems models illustrate health
      promotion: educational practice, group- or population-based targets, community
      environment and social determinants of health. There is little room for patients
      in elaborating the models, as they have little role in health care systems. The
      definitions of prevention, health promotion and patient education greatly differ
      from one model to another. DISCUSSION: Little is known about practical
      implementation of the models; assessment data are scarce. Some elements valued by
      health promotion could be integrated to health care: empowerment of citizens,
      addressing community environment; increased involvement in local health
      professionals' networks; integration of individual and collective approaches
      within the same health care facilities to address simultaneously individual
      customization, efficiency and equity objectives. These developments may call for
      adaptation in vocational training and continuous professional development:
      communication skills, awareness to public health concepts, and early and
      longitudinal exposure to community-based learning experiences for students.

PMID- 25943797
TI  - The African CDC and WHO AFRO.

PMID- 25943798
TI  - Cognitive ageing: wisdom in the bigger picture.

PMID- 25943799
TI  - Reducing the burden of iatrogenic harm in children.

PMID- 25943801
TI  - Obama steps up US campaign on climate change.

PMID- 25943802
TI  - ECDC left leaderless after EU vote.

PMID- 25943803
TI  - Yemen health situation "moving from a crisis to a disaster".

PMID- 25943807
TI  - Pedro L Alonso: mapping out the future of malaria control.

PMID- 25943808
TI  - What kind of society do we want: getting the balance right.

PMID- 25943809
TI  - Henry Harris.

PMID- 25943810
TI  - Is precision medicine the route to a healthy world?

PMID- 25943811
TI  - beta blockers in patients with heart failure and atrial fibrillation.

PMID- 25943812
TI  - beta blockers in patients with heart failure and atrial fibrillation - Authors'
      reply.

PMID- 25943814
TI  - Alcohol-related deaths: is misinformation hindering care improvement?

PMID- 25943813
TI  - beta blockers in patients with heart failure and atrial fibrillation.

PMID- 25943815
TI  - The Middle East Cancer Consortium promotes palliative care.

PMID- 25943816
TI  - Cigarette smoking among Chinese medical staff.

PMID- 25943817
TI  - Dengue fever in China.

PMID- 25943818
TI  - Department of Error.

PMID- 25943819
TI  - Road traffic injury and rescue system in China.

PMID- 25943820
TI  - Department of Error.

PMID- 25943821
TI  - Department of Error.

PMID- 25943822
TI  - Bloody diarrhoea in a hunger striker: starvation colitis.

PMID- 25943823
TI  - Are all new allergens in TRUE Test(r) essential for a baseline set?

PMID- 25943824
TI  - Rapid identification of anti-inflammatory compounds from Tongmai Yangxin Pills by
      liquid chromatography with high-resolution mass spectrometry and chemometric
      analysis.
AB  - We present an integrated approach to rapidly identify anti-inflammatory compounds
      of TongmaiYangxin Pills (TMYXP), a botanical drug for the treatment of
      cardiovascular disease. Liquid chromatography coupled with high-resolution mass
      spectrometry was used to analyze the chemical composition of TMYXP. Eighty
      compounds of TMYXP including flavonoids, coumarins, iridoid glycosides, saponins,
      and lignans, were identified unambiguously or tentatively. After the rapid
      isolation and bioassay, 18 fractions of TMYXP were obtained and their anti
      inflammatory activities were evaluated in lipopolysaccharide-stimulated RAW 264.7
      macrophages. We performed chemometric analysis to reveal the correlation between
      the chemical and pharmacological information of the fractions to facilitate the
      identification of active compounds. To verify the reliability of the proposed
      method in discovering active components from a complex mixture, activities of
      seven compounds, which were positively or negatively related to bioactivity
      according to calculation, were validated in vitro. Results indicated that six
      active compounds with high R values exerted certain anti-inflammatory effects in
      a dose-dependent manner with IC50 values of 53.6-204.1 MUM. Our findings suggest
      that the integrated use of identification based on high-resolution mass
      spectrometry and chemometric methods could rapidly identify active compounds from
      complex mixture of natural products. 

PMID- 25943825
TI  - Urine-based viral diagnostics: an innovation in waiting.

PMID- 25943826
TI  - Mechanistic versus allometric models for the prediction of drug clearance in
      neonates (<3 months of age).

PMID- 25943827
TI  - Response to letter to the editor from Dr. Mahmood: Original publication:
      "Predicting the 'first dose in children' of CYP3A-metabolized drugs: evaluation
      of scaling approaches and insights into the CYP3A7-CYP3A4 switch at young ages".

PMID- 25943829
TI  - The prevalence and predictors of type two diabetes mellitus in people with
      schizophrenia: a systematic review and comparative meta-analysis.
AB  - OBJECTIVE: To conduct a meta-analysis investigating the prevalence of type two
      diabetes mellitus (T2DM) in people with schizophrenia compared to controls.
      METHOD: Systematic review of electronic databases from inception till November
      2014. Articles reporting the prevalence of T2DM in people with schizophrenia and
      healthy controls (without mental illness) were included. Two independent authors
      conducted searches and extracted data. A random effects relative risks (RR) meta
      analysis was conducted. RESULTS: Twenty-five studies including 145,718
      individuals with schizophrenia (22.5-54.4 years) and 4,343,407 controls were
      included. The prevalence of T2DM in people with schizophrenia was 9.5% (95% CI =
      7.0-12.8, n = 145,718) and 10.75% (95% CI 7.44-14.5%, n = 2698) in studies
      capturing T2DM according to recognized criteria. The pooled RR across all studies
      was 1.82 (95% CI = 1.56-2.13; = 4,489,125). Subgroup analyses found a RR of 2.53
      (95% CI = 1.68-3.799, n = 17,727) in studies ascertaining T2DM according to
      recognized criteria and RR 1.65 (95% CI = 1.34-2.03, n = 4,243,389) in studies
      relying on T2DM determined through medical records. CONCLUSION: People with
      schizophrenia are at least double the risk of developing T2DM according to
      recognized T2DM criteria. Proactive lifestyle and screening programmes should be
      given clinical priority.

PMID- 25943830
TI  - Development of a fast high performance liquid chromatographic screening system
      for eight antidiabetic drugs by an improved methodology of in-silico robustness
      simulation.
AB  - Robustness of RP-HPLC methods is a crucial method quality attribute which has
      gained an increasing interest throughout the efforts to apply quality by design
      concepts in analytical methodology. Improvement to design space modeling
      approaches to represent method robustness was the goal of many previous works.
      Modeling of design spaces regarding to method robustness fulfils quality by
      design essence of ensuring method validity throughout the design space. The
      current work aimed to describe an improvement to robustness modeling of design
      spaces in context of RP-HPLC method development for screening of eight
      antidiabetic drugs. The described improvement consisted of in-silico simulation
      of practical robustness testing procedures thus had the advantage of modeling
      design spaces with higher confidence in estimated of method robustness. The
      proposed in-silico robustness test was performed as a full factorial design of
      simulated method conditions deliberate shifts for each predicted point in
      knowledge space with modeling error propagation. Design space was then calculated
      as zones exceeding a threshold probability to pass the simulated robustness
      testing. Potential design spaces were mapped for three different stationary
      phases as a function of gradient elution parameters, pH and ternary solvent
      ratio. A robust and fast separation for the eight compounds within less than 6
      min was selected and confirmed through experimental robustness testing. The
      effectiveness of this approach regarding definition of design spaces with ensured
      robustness and desired objectives was demonstrated.

PMID- 25943831
TI  - Carbonized polydopamine as coating for solid-phase microextraction of
      organochlorine pesticides.
AB  - A facile preparation route for coating a stainless steel fiber with carbonaceous
      material derived from polydopamine is reported in this work. The self-oxidation
      induced polymerization of dopamine in alkaline solution enables growth of
      polydopamine on the inert surface of the fiber. The robust adhesion of dopamine
      to metal oxides ensured sufficient stability of the polymer coating. After
      carbonization of the polymer coating, the obtained carbon coated fiber was
      utilized for solid-phase microextraction and exhibited effectiveness in the
      extraction of organochlorine pesticides (OCPs) from aqueous solution. Extraction
      time, agitation speed and salt addition were optimized. The possible interference
      of humic acid on the extraction of these analytes was also investigated. The
      results showed that most of the analytes could be detected efficiently in the
      presence of humic acid at a concentration of 20mg/L. Under the optimized
      conditions, enrichment factors of 102-757 were obtained for the selected OCPs in
      aqueous solution. The proposed method provided low limits of detection (1.4-15
      ng/L), good linearity (correlation coefficients>0.9971) and acceptable precision
      (relative standard deviations<16.3%).

PMID- 25943832
TI  - Multi-objective optimization for the economic production of d-psicose using
      simulated moving bed chromatography.
AB  - The biocatalytic production of rare carbohydrates from available sugar sources
      rapidly gains interest as a route to acquire industrial amounts of rare sugars
      for food and fine chemical applications. Here we present a multi-objective
      optimization procedure for a simulated moving bed (SMB) process for the
      production of the rare sugar d-psicose from enzymatically produced mixtures with
      its epimer d-fructose. First, model parameters were determined using the inverse
      method and experimentally validated on a 2-2-2-2 lab-scale SMB plant. The
      obtained experimental purities (PUs) were in excellent agreement with the
      simulated data derived from a transport-dispersive true-moving bed model
      demonstrating the feasibility of the proposed design. In the second part the
      performance of the separation was investigated in a multi-objective optimization
      study addressing the cost-contributing performance parameters productivity (PR)
      and desorbent requirement (DR) as a function of temperature. While rare sugar SMB
      operation under conditions of low desorbent consumption was found to be widely
      unaffected by temperature, SMB operation focusing on increased PR significantly
      benefited from high temperatures, with possible productivities increasing from
      3.4kg(Lday)(-1) at 20 degrees C to 5kg(Lday)(-1) at 70 degrees C, indicating that
      decreased selectivity at higher temperatures could be fully compensated for by
      the higher mass transfer rates, as they translate into reduced switch times and
      hence higher PR. A DR/PR Pareto optimization suggested a similar but even more
      pronounced trend also under relaxed PU requirements, with the PR increasing from
      4.3kg(Lday)(-1) to a maximum of 7.8kg(Lday)(-1) for SMB operation at 50 degrees C
      when the PU of the non-product stream was reduced from 99.5% to 90%. Based on the
      in silico optimization results experimental SMB runs were performed yielding
      considerable PRs of 1.9 (30 degrees C), 2.4 (50 degrees C) and 2.6kg(Lday)(-1)
      (70 degrees C) with rather low DR (27L per kg of rare sugar produced) on a lab
      scale SMB installation. 

PMID- 25943833
TI  - A chemometric-assisted method based on gas chromatography-mass spectrometry for
      metabolic profiling analysis.
AB  - An automatic and efficient data analysis method for comprehensive metabolic
      profiling analysis is urgently required. In this study, a new chemometric
      assisted method for metabolic profiling analysis (CAMMPA) was developed to
      discover potentially valuable metabolites automatically and efficiently. The
      proposed method mainly consists of three stages. First, automatic chromatographic
      peak detection is performed based on the total ion chromatograms of samples to
      extract chromatographic peaks that can be accurately quantified. Second, a novel
      peak-shift alignment technique based on peak detection results is implemented to
      resolve time-shift problems across samples. Consequently, aligned results,
      including aligned chromatograms, and peak area tables, among others, can be
      successfully obtained. Third, statistical analysis using results from
      unsupervised and supervised classification results, together with ANOVA and
      partial least square-discriminate analysis, is performed to extract potential
      metabolites. To demonstrate the proposed technique, a complex GC-MS metabolic
      profiling dataset was measured to identify potential metabolites in tobacco
      plants of different growth stages as well as different plant tissues after
      maturation. Results indicated that the efficiency of the routine metabolic
      profiling analysis procedure can be significantly improved and potential
      metabolites can be accurately identified with the aid of CAMMPA. 

PMID- 25943834
TI  - Editorial - in vivo analysis.

PMID- 25943835
TI  - Screening for breast cancer by molecular testing for three founder mutations in
      the BRCA1 and BRCA2 genes among women of Ashkenazi Jewish heritage.

PMID- 25943836
TI  - Neurological soft signs in children with attention deficit hyperactivity
      disorder: Their relationship to executive function and parental neurological soft
      signs.
AB  - The correlations between neurological soft signs (NSS) in children with attention
      deficit hyperactivity disorder (ADHD) and their executive function, symptoms of
      inattention, and hyperactivity-impulsivity and the NSS of their parents remain
      unclear. This study aimed to examine: (1) the prevalence of NSS in children with
      ADHD and their parents; (2) the correlation between the NSS of children with ADHD
      and the NSS of their parents; and (3) the correlation between the NSS of children
      with ADHD and their executive function and symptoms. NSS were assessed with the
      Cambridge Neurological Inventory (CNI) in 57 children with ADHD (and 80 parents)
      and 60 healthy children (and 75 parents). Executive function was measured with
      the Behavioral Rating Inventory of Executive Function (BRIEF). Children with ADHD
      and their parents had significantly higher NSS than normal children and their
      parents, respectively, and the NSS of children with ADHD were correlated more
      strongly with the NSS of their fathers than their mothers. No correlation was
      found between NSS and BRIEF executive function, but Disinhibition in children
      with ADHD was significantly correlated with hyperactivity-impulsivity symptoms.
      Paternal and maternal NSS provided different predictions for child NSS. It may be
      that NSS are more likely to be genetically transmitted by fathers. 

PMID- 25943837
TI  - What is your diagnosis? Bovine synovial fluid.

PMID- 25943838
TI  - Natural history and outcomes in drug-induced autoimmune hepatitis.
AB  - AIM: Drug-induced autoimmune hepatitis (DIAIH) remains poorly characterized. Our
      aim was to assess natural history and outcomes in DIAIH. METHODS: This was a
      retrospective cohort study. RESULTS: Eighty-two patients with autoimmune
      hepatitis (AIH) were identified, 11 (13.4%) with DIAIH, implicated drugs being
      nitrofurantoin (n = 4), statins (n = 4), herbal remedies (n = 2) and diclofenac
      (n = 1). Female sex, acute onset, elevated serum globulins/immunoglobulin G,
      fibrosis stage (Ishak), cirrhosis at onset, moderate-severe portal inflammation,
      interface and lobular hepatitis, remission, relapse and poor outcome were similar
      in those with DIAIH and AIH (P > 0.05). The former were however more likely to be
      aged 60 years or more and take longer to relapse on immunosuppression
      discontinuation (P = <0.05). On Kaplan-Meier analysis, probability of poor
      outcome was similar in those with DIAIH and AIH (log-rank test, 0.339). On
      comparing those with (n = 4) and without nitrofurantoin (n = 7) DIAIH, the former
      were older, had longer duration of drug use prior to DIAIH diagnosis, higher
      fibrosis stage and were less likely to relapse upon immunosuppression
      discontinuation. CONCLUSION: Approximately 15% of patients with AIH have DIAIH
      with similar outcomes, although the latter are older with a propensity for late
      relapse, mandating long-term follow up.

PMID- 25943839
TI  - A comparison of European and US guidelines for familial hypercholesterolaemia.
AB  - PURPOSE OF REVIEW: To compare the European and US guidelines for familial
      hypercholesterolaemia, but also all the European and US position/consensus papers
      on heterozygous and homozygous familial hypercholesterolaemia published recently.
      RECENT FINDINGS: It has been established that the prevalence of familial
      hypercholesterolaemia was previously markedly underestimated. The disease is
      characterized by a lifelong significant increase in LDL cholesterol (LDL-C)
      levels and therefore premature atherosclerotic cardiovascular disease.
      Recommendations on familial hypercholesterolaemia have been included as a special
      chapter in the recent European (European Society of Cardiology/European
      Atherosclerosis Society) guidelines on dyslipidaemia, whereas in the new US
      (American College of Cardiology/American Heart Association) lipid guidelines they
      have been included only generally and these guidelines avoid mentioning familial
      hypercholesterolaemia explicitly. Both of these guidelines recommend statins in
      high doses as the treatment option. However, in the American College of
      Cardiology/American Heart Association guidelines, there is no requirement to
      attain a specific LDL-C target which is different from the European Society of
      Cardiology/European Atherosclerosis Society guidelines. Although these two
      guidelines differ markedly in a number of aspects, they both stress the need to
      diagnose familial hypercholesterolaemia patients as early as possible and to
      treat them with intensive LDL-C-lowering therapy. SUMMARY: All the guidelines and
      consensus papers stress that earlier diagnosis and effective treatment can
      markedly improve life expectancy among familial hypercholesterolaemia patients.

PMID- 25943840
TI  - Early initiation of statin treatment in children with familial
      hypercholesterolaemia.
AB  - PURPOSE OF REVIEW: This article provides recent insights on the early onset of
      atherosclerosis in heterozygous familial hypercholesterolemia and reports on
      novel treatment options as well as on the consequences of long-term statin use in
      childhood. RECENT FINDINGS: Children with familial hypercholesterolemia have
      greater mean carotid intima-media thickness (cIMT) than their unaffected siblings
      even before the age of 8 years, which is several years earlier than previously
      reported. In those children, 2 years of rosuvastatin treatment resulted in
      slowing of the cIMT progression. In addition, in a 10-year follow-up study after
      a pravastatin intervention trial, long-term statin therapy in young adult
      familial hypercholesterolemia patients was associated with normalization of cIMT
      progression and appeared effective in prevention of very premature cardiovascular
      events. These effects were observed without untoward safety concerns. However, a
      majority of these young adults did not reach cholesterol goals according to
      general guidelines, indicating the need for improvement of treatment in this
      patient group. SUMMARY: The importance, efficacy and safety of early initiation
      statin therapy in familial hypercholesterolemia children were further confirmed
      by recent findings. Nevertheless, to reach current treatment goals, the use of
      more potent statins is required and has been proven well tolerated and effective
      in young children.

PMID- 25943841
TI  - Muscle-related side-effects of statins: from mechanisms to evidence-based
      solutions.
AB  - PURPOSE OF REVIEW: This article highlights the recent findings regarding statin
      associated muscle side effects, including mechanisms and treatment as well as the
      need for more comprehensive clinical trials in statin myalgia. RECENT FINDINGS:
      Statin myalgia is difficult to diagnose and treat, as major clinical trials have
      not routinely assessed muscle side-effects, there are few clinically relevant
      biomarkers and assessment tools for the symptoms, many apparent statin-related
      muscle symptoms may be nonspecific and related to other drugs or health
      conditions, and prevalence estimates vary widely. Data thus suggest that only 30
      50% of patients with self-reported statin myalgia actually experience muscle pain
      on statins during blinded, placebo-controlled trials. In addition, evidence to
      date involving mechanisms underlying statin myalgia and its range of symptoms and
      presentations supports the hypothesis that there are multiple, interactive and
      potentially additive mechanisms underlying statin-associated muscle side-effects.
      SUMMARY: There are likely multiple and interactive mechanisms underlying statin
      myalgia, and recent studies have produced equivocal data regarding prevalence of
      statin-associated muscle side-effects, contributing factors and effectiveness of
      common interventions. Therefore, more clinical trials on statin myalgia are
      critical to the field, as are systematic resources for quantifying, predicting
      and reporting statin-associated muscle side-effects.

PMID- 25943842
TI  - 'LDL-C' = LDL-C + Lp(a)-C: implications of achieved ultra-low LDL-C levels in the
      proprotein convertase subtilisin/kexin type 9 era of potent LDL-C lowering.
AB  - PURPOSE OF REVIEW: The measurement that is termed 'LDL-cholesterol' (LDL-C)
      includes the cholesterol content of lipoprotein(a) [Lp(a)-C], which can
      contribute approximately 30-45% to measured LDL-C levels as a percentage of its
      mass. We review the implications of achieved very low LDL-C levels in patients
      treated with potent LDL-C-lowering agents in the context of varying Lp(a) levels.
      RECENT FINDINGS: Combination therapy with statins, ezetimibe, and proprotein
      convertase subtilisin/kexin type 9 (PCSK9) inhibitors can lower LDL-C to
      unprecedentedly low levels. Recent PCSK9 trials have shown that routine
      achievement of mean LDL-C less than 50 mg/dl is feasible, along with the modest
      reductions in Lp(a). Many patients will achieve LDL-C less than 25 mg/dl with
      concomitantly elevated Lp(a) levels that contribute substantially to the measured
      'LDL-C'. Therefore, it is possible that some of these patients may have little to
      no circulating LDL-C. SUMMARY: As the new era of ultralow LDL-C levels ensues, it
      is imperative to understand the contribution of Lp(a)-C to measured LDL-C and the
      consequences of achieving ultralow or potentially absent LDL-C in the setting of
      elevated Lp(a) levels and possibly free apo(a). We review this concept and
      suggest avenues of research, including analyses of existing datasets in current
      clinical trials and new research studies, to understand its pathophysiological
      and clinical significance.

PMID- 25943843
TI  - Sufficient collateral blood supply from accessory middle cerebral artery in a
      patient with acute ischemic stroke.
AB  - We reported a case of acute embolic occlusion of the middle cerebral artery with
      a patent accessory middle cerebral artery. Because of the presence of sufficient
      collateral blood supply from the accessory middle cerebral artery, the patient
      only underwent transient ischemic attack and did not need endovascular treatment.
      There was mild infarction in the basal ganglia and temporal lobe, NIHSS score of
      the patient at discharge seven days after stroke onset was 0, and modified Rankin
      scale score at 90 days was 0. 

PMID- 25943845
TI  - Transforaminal approach for cerebral dural arteriovenous fistula embolization.
AB  - A transverse sinus dural arteriovenous fistula (DAVF) not easily accessible by
      standard transfemoral (transarterial or transvenous) endovascular approaches is
      presented. An enlarged transosseous retromastoid foramen harboring the occipital
      artery branch feeding the lesion was identified on CT angiogram (CTA). Curative
      Onyx embolization was achieved via percutaneous CT-guided direct puncture of the
      transosseous occipital arterial branch followed by microcatheter navigation
      through the needle distally towards the site of the fistula. 

PMID- 25943844
TI  - Use of a new soft and long coil reduces the number of coils to embolize a small
      aneurysm.
AB  - BACKGROUND: In embolizing a cerebral aneurysm, achievement of a high-volume
      embolization ratio (VER: volume of inserted coils / aneurysm volume) is important
      because it may prevent coil compaction and recanalization. The goal of the study
      is to examine whether use of softer and longer coils gives an adequate VER with
      fewer coils, particularly for small aneurysms. METHODS: Aneurysm volumes, VERs,
      and numbers of inserted coils were investigated in 23 cases of small aneurysms
      embolized using Infini coils, a long soft coil with a primary diameter of 0.010
      inches (Infini group). An aneurysm volume- and VER-matched control (non-Infini)
      group of 59 cases was selected from patients treated at our facility. Data were
      also compared between subgroups of patients (n = 18 and n = 34 in the Infini and
      non-Infini groups, respectively) who were not treated with thicker coils with
      primary diameters of 0.0135-0.015 inches (18-type coils), since these coils
      affect the number of coils by increasing VER rapidly. RESULTS: Average aneurysm
      volumes and VERs did not differ significantly between the Infini and non-Infini
      groups. Significantly fewer coils were used per 0.1 ml aneurysm volume in the
      Infini group (4.08 coils in average) compared with the non-Infini group (5.67) (p
      < 0.001). In the non-18-type subgroups, the number of coils used remained
      significantly smaller in the Infini group (4.49) compared with the non-Infini
      group (6.72), (p < 0.001). CONCLUSION: To achieve VER >=20%, use of Infini coils
      significantly decreased the number of coils required per unit volume of a small
      aneurysm.

PMID- 25943846
TI  - Carotid and vertebral injury study (CAVIS) technique for characterization of
      blunt traumatic aneurysms with reliability assessment.
AB  - Traumatic aneurysms occur in up to 20% of blunt traumatic extracranial carotid
      artery injuries. Currently there is no standardized method for characterization
      of traumatic aneurysms. For the carotid and vertebral injury study (CAVIS), a
      prospective study of traumatic cerebrovascular injury, we established a method
      for aneurysm characterization and tested its reliability. Saccular aneurysm size
      was defined as the greatest linear distance between the expected location of the
      normal artery wall and the outer edge of the aneurysm lumen ("depth"). Fusiform
      aneurysm size was defined as the "depth" and longitudinal distance ("length")
      paralleling the normal artery. The size of the aneurysm relative to the normal
      artery was also assessed. Reliability measurements were made using four raters
      who independently reviewed 15 computed tomographic angiograms (CTAs) and 13
      digital subtraction angiograms (DSAs) demonstrating a traumatic aneurysm of the
      internal carotid artery. Raters categorized the aneurysms as either "saccular" or
      "fusiform" and made measurements. Five scans of each imaging modality were
      repeated to evaluate intra-rater reliability. Fleiss's free-marginal multi-rater
      kappa (kappa), Cohen's kappa (kappa), and interclass correlation coefficient
      (ICC) determined inter- and intra-rater reliability. Inter-rater agreement as to
      the aneurysm "shape" was almost perfect for CTA (kappa = 0.82) and DSA (kappa =
      0.897). Agreements on aneurysm "depth," "length," "aneurysm plus parent artery,"
      and "parent artery" for CTA and DSA were excellent (ICC > 0.75). Intra-rater
      agreement as to aneurysm "shape" was substantial to almost perfect (kappa >
      0.60). The CAVIS method of traumatic aneurysm characterization has remarkable
      inter- and intra-rater reliability and will facilitate further studies of the
      natural history and management of extracranial cerebrovascular traumatic
      aneurysms. 

PMID- 25943847
TI  - Neurological recovery after coma related to diffuse cerebral venous sinus
      thrombosis. Interest in thrombi-aspiration with Penumbra system.
AB  - We report a young man with a history of deep coma secondary to an extensive
      superior sagittal sinus thrombosis despite full systemic anticoagulation.
      Endovascular treatment combining a 5 Max ACE reperfusion catheter (Penumbra) and
      Solitaire (Covidien) retrieval device permitted revascularization of the superior
      sagittal sinus with restoration of anterograde venous flow. This treatment led to
      the disappearance of cytotoxic edema on MRI and to a neurological improvement
      with a modified Rankin scale score of 2 after two months. Our experience shows
      that this technique provides a useful and safe tool after failure of
      anticoagulation in cerebral venous sinus thrombosis. 

PMID- 25943848
TI  - Efficacy of a unique straight, conformable, bare platinum coil in the treatment
      of cavernous sinus dural arteriovenous fistula.
AB  - In embolization of a cavernous sinus (CS) by transvenous embolization (TVE) for a
      CS dural arteriovenous fistula (DAVF), selection of embolization coils is
      difficult owing to the complex anatomical structure of the CS. Moreover,
      overpacking of the CS with embolization coils may cause permanent cranial nerve
      palsies. The ED coil-10 (EDC-10) infini is an extremely soft platinum coil
      without shape-memory that has excellent conformability with surrounding
      structures. The goal of this study was to evaluate use of the EDC-10 infini coil
      for embolization of a CS DAVF. Six patients with a CS DAVF were treated with TVE.
      Refluxing cerebral and ophthalmic veins were embolized with shape-memory type
      coils other than EDC-10 infini, and CSs were embolized with the EDC-10 infini
      coils. In five cases, CSs were loosely embolized with EDC-10 infini coils. In one
      case, reflux of the cerebral vein worsened from the CS during the procedure, and
      embolization of the CS tightly using three-dimensional shape-memory type coils
      other than EDC-10 infini. Overall, three to 19 (average 7.3) coils were used fozr
      each CS and the total coil volume was 33-284 (average 95.1) mm(3) in each CS.
      Postoperative transient abducens palsy occurred in two cases, but both patients
      recovered completely. There was no case of recurrence. The EDC-10 infini coil
      showed excellent conformability with the complex inner structure of the CS and
      excellent safety without postoperative permanent cranial nerve palsy. 

PMID- 25943849
TI  - Neuromeningeal access for transarterial intravenous carotid-cavernous fistula
      embolization.
AB  - While numerous endovascular access routes have been described for carotid
      cavernous fistula (CCF) treatment, transarterial embolization via the
      neuromeningeal trunk of the ascending pharyngeal artery is typically avoided due
      to the risk of cranial nerve palsy or non-target embolization via external-to
      internal carotid anastamoses. We present the case of a dural CCF in which access
      to the venous side of the fistula was achieved via the neuromeningeal trunk and
      allowed for curative transarterial intravenous coil/liquid embolic embolization
      of the lesion. The utility of a transarterial intravenous approach in the face of
      venous sinus occlusion is highlighted. The neuromeningeal trunk should not be
      overlooked as a potential access route for transarterial intravenous CCF
      embolization in cases where traditional endovascular access is limited; this
      approach does not carry the same risks that are generally associated with pure
      transarterial embolization along this pathway. 

PMID- 25943851
TI  - Molecular identification of GnIH/GnIHR signal and its reproductive function in
      protogynous hermaphroditic orange-spotted grouper (Epinephelus coioides).
AB  - Gonadotropin-inhibitory hormone (GnIH) and its receptor (GnIHR) play an important
      role in reproduction regulation in birds, mammals and some teleost species. In
      protogynous hermaphroditic orange-spotted grouper (Epinephelus coioides), the
      GnIH/GnIHR signaling pathway and its reproductive function have not been
      addressed yet. In this study, GnIH and GnIHR in orange-spotted grouper were
      characterized. gGnIH possessed three putative peptides (gGnIH-I, -II, -III),
      while gGnIHR showed the characteristics of G protein-coupled receptor and was
      clustered with GPR147. Functional assays demonstrated that three synthetic gGnIH
      peptides significantly decreased the forskolin-induced CRE promoter activity, but
      only gGnIH-I could significantly decrease SRE promoter activity in COS-7 cells
      transfected with gGnIHR. During the process of ovarian differentiation and
      development, gGnIH mRNA level in hypothalamus was low at the gonadal primordium
      stage with gonia, then increased significantly at the early differentiated gonad
      with primary growth oocytes, while decreased significantly at the developing
      gonads with cortical-alveolus and vitellogenic stage oocytes. During MT-induced
      sex reversal, gGnIH mRNA level in hypothalamus increased significantly when the
      fish completely reversed from female to male. However, gGnIHR mRNA level in
      pituitary decreased significantly in intersex and completely reversed male fish.
      Intraperitoneal injection (i.p.) of three gGnIH peptides significantly decreased
      GnRH1 mRNA levels in hypothalamus, and gGnIH-II significantly inhibited synthesis
      of LHbeta in pituitary. In summary, we firstly identified the GnIH/GnIHR signal
      in protogynous orange-spotted grouper, which might be involved in the regulation
      of the reproductive function of sex differentiation, gonadal development and sex
      reversal via regulating the synthesis of both GnRH and GtH. 

PMID- 25943852
TI  - A meta-analysis of active video games on health outcomes among children and
      adolescents.
AB  - This meta-analysis synthesizes current literature concerning the effects of
      active video games (AVGs) on children/adolescents' health-related outcomes. A
      total of 512 published studies on AVGs were located, and 35 articles were
      included based on the following criteria: (i) data-based research articles
      published in English between 1985 and 2015; (ii) studied some types of AVGs and
      related outcomes among children/adolescents and (iii) had at least one comparison
      within each study. Data were extracted to conduct comparisons for outcome
      measures in three separate categories: AVGs and sedentary behaviours, AVGs and
      laboratory-based exercise, and AVGs and field-based physical activity. Effect
      size for each entry was calculated with the Comprehensive Meta-Analysis software
      in 2015. Mean effect size (Hedge's g) and standard deviation were calculated for
      each comparison. Compared with sedentary behaviours, AVGs had a large effect on
      health outcomes. The effect sizes for physiological outcomes were marginal when
      comparing AVGs with laboratory-based exercises. The comparison between AVGs and
      field-based physical activity had null to moderate effect sizes. AVGs could yield
      equivalent health benefits to children/adolescents as laboratory-based exercise
      or field-based physical activity. Therefore, AVGs can be a good alternative for
      sedentary behaviour and addition to traditional physical activity and sports in
      children/adolescents. 

PMID- 25943850
TI  - Emergent extracranial internal carotid artery stenting and mechanical
      thrombectomy in acute ischaemic stroke.
AB  - OBJECTIVE: Tandem occlusions involving both the extracranial internal carotid
      artery (ICA) and an intracranial artery typically respond poorly to intravenous
      (IV) tissue plasminogen activator (t-PA). We retrospectively review our
      experience with proximal ICA stenting and stent-assisted thrombectomy of the
      distal artery. METHODS: The data included patients that underwent carotid
      stenting and mechanical thrombectomy between 2012-2013. Radiographic, clinical,
      and procedural data were drawn from case notes, imaging records and discharge
      reports. Clinical outcomes were evaluated using the National Institutes of Health
      Stroke Scale (NIHSS) and the modified Rankin scale (mRs). RESULTS: Seven
      patients, with a mean age of 66.4 years and a mean admission NIHSS of 18.3,
      underwent this procedure and were included. Each presented with an occlusion of
      the proximal ICA, with additional occlusions of the ICA terminus (n = 3), middle
      cerebral artery (n = 5), or anterior cerebral artery (n = 1). Recanalisation of
      all identified occlusions was achieved in all patients, with a Thrombolysis in
      Myocardial Infarction (TIMI) score of 3 and a Thrombolysis in Cerebral Infarction
      (TICI) score >2b achieved in each case. Mean time from onset of stroke symptoms
      to recanalisation was 287 min; mean time from first angiography to recanalisation
      was 52 min. Intracranial haemorrhages occurred in two patients, with no increase
      in NIHSS. There were no mortalities. Mean NIHSS at discharge was 4.9, and mRs at
      90 days was one in all patients. CONCLUSIONS: Treatment of tandem extracranial
      ICA and intracranial occlusions in the setting of acute ischaemic stroke with
      extracranial carotid artery stenting followed by adjunctive intracranial
      mechanical thrombectomy is both safe and effective, but further evaluation of
      this treatment modality is necessary.

PMID- 25943853
TI  - Higenamine 4'-O-beta-d-glucoside in the lotus plumule induces glucose uptake of
      L6 cells through beta2-adrenergic receptor.
AB  - Hypoglycemic effect is an efficient means to modulate elevated blood glucose
      levels in patients with diabetes. We found that the extract of lotus plumule (the
      germ of Nelumbo nucifera Gaertn. seed) showed potent glucose uptake enhancement
      activity against L6 myotubes, which results in a hypoglycemic effect. This
      activity was further investigated, and an active constituent was identified as a
      single bioactive compound, higenamine 4'-O-beta-d-glucoside. Mechanistic studies
      employing phosphatidylinositol 3-kinase (PI3K) inhibitor, AMP-activated protein
      kinase (AMPK) inhibitor, or adrenergic receptor antagonist showed that the
      compound induced its activity through beta2-adrenergic receptor. Patients with
      type II diabetes mellitus frequently develop insulin resistance. Owing to the
      differences between the mechanism of action of insulin and of the isolated
      compound, the compound or lotus plumule itself may have the possibility of
      modulating blood glucose levels in insulin-resistant patients effectively.

PMID- 25943854
TI  - Potent antimicrobial agents against azole-resistant fungi based on
      pyridinohydrazide and hydrazomethylpyridine structural motifs.
AB  - Schiff base derivatives have recently been shown to possess antimicrobial
      activity, and these derivatives include a limited number of salicylaldehyde
      hydrazones. To further explore this structure-activity relationship between
      salicylaldehyde hydrazones and antifungal activity, we previously synthesized and
      analyzed a large series of salicylaldehyde and formylpyridinetrione hydrazones
      for their ability to inhibit fungal growth of both azole-susceptible and azole
      resistant species of Candida. While many of these analogs showed excellent growth
      inhibition with low mammalian cell toxicity, their activity did not extend to
      azole-resistant species of Candida. To further dissect the structural features
      necessary to inhibit azole-resistant fungal species, we synthesized a new class
      of modified salicylaldehyde derivatives and subsequently identified a series of
      modified pyridine-based hydrazones that had potent fungicidal antifungal activity
      against multiple Candida spp. Here we would like to present our synthetic
      procedures as well as the results from fungal growth inhibition assays, mammalian
      cell toxicity assays, time-kill assays and synergy studies of these novel
      pyridine-based hydrazones on both azole-susceptible and azole-resistant fungal
      species. 

PMID- 25943855
TI  - CMV Primary Infection Is Associated With Donor-Specific T Cell Hyporesponsiveness
      and Fewer Late Acute Rejections After Liver Transplantation.
AB  - Viral infections, including cytomegalovirus (CMV), abrogate transplantation
      tolerance in animal models. Whether this also occurs in humans remains elusive.
      We investigated how CMV affects T cells and rejection episodes after liver
      transplantation (LT). Phenotype and alloreactivity of peripheral and allograft
      infiltrating T cells from LT patients with different CMV status were analyzed by
      flow cytometry. The association of CMV status with early and late acute rejection
      was retrospectively analyzed in a cohort of 639 LT patients. CMV-positivity was
      associated with expansion of peripheral effector memory T cell subsets after LT.
      Patients with CMV primary infection showed donor-specific CD8(+) T cell
      hyporesponsiveness. While terminally differentiated effector memory cells
      comprised the majority of peripheral donor-specific CD8(+) T cells in CMV primary
      infection patients, they were rarely present in liver allografts. Retrospective
      analysis showed that R(-) D(+) serostatus was an independent protective factor
      for late acute rejection by multivariate Cox regression analysis (hazard ratio
      [HR] = 0.18, 95% CI = 0.04-0.86, p = 0.015). Additionally, CMV primary infection
      patients showed the highest Vdelta1/Vdelta2 gammadelta T cell ratio, which has
      been shown to be associated with operational tolerance after LT. In conclusion,
      our data suggest that CMV primary infection may promote tolerance to liver
      allografts, and CMV status should be considered when tapering or withdrawing
      immunosuppression. 

PMID- 25943856
TI  - Standardized classification unsuitable for spontaneous reporting: the example of
      osteonecrosis of the jaw.
AB  - OBJECTIVE: This study assessed the impact of using a standardized definition of
      bisphosphonate-related osteonecrosis of the jaw (BRONJ) in the analysis of a
      spontaneous reporting database. METHODS: All notifications of osteonecrosis of
      the jaw (ONJ) in the French National Pharmacovigilance Database as of 31 December
      2013 were analyzed. First, we considered all reports of ONJ with bisphosphonates
      as BRONJ. Second, we applied the 2014 definition of BRONJ from the American
      Association of Oral and Maxillofacial Surgeons (AAOMS), retaining only
      bisphosphonates as antiresorptive medication. In the absence of any one of these
      criteria, or missing data, cases were not considered as BRONJ. RESULTS: The first
      analysis found 158 cases of ONJ, among which 153 were associated with
      bisphosphonate use. The second analysis identified only 43 cases of BRONJ
      (28.1%). CONCLUSION: The definition of BRONJ as laid down by the AAOMS is not
      suitable for use in spontaneous reporting database. The use of the AAOMS
      definition alone should be avoided, as it leads to the exclusion of over 70% of
      cases. When cases of ONJ are identified, all results should be presented
      including confirmed and excluded cases.

PMID- 25943857
TI  - Identifying Key Attributes for Protein Beverages.
AB  - This study identified key attributes of protein beverages and evaluated effects
      of priming on liking of protein beverages. An adaptive choice-based conjoint
      study was conducted along with Kano analysis to gain insight on protein beverage
      consumers (n = 432). Attributes evaluated included label claim, protein type,
      amount of protein, carbohydrates, sweeteners, and metabolic benefits. Utility
      scores for levels and importance scores for attributes were determined.
      Subsequently, two pairs of clear acidic whey protein beverages were manufactured
      that differed by age of protein source or the amount of whey protein per serving.
      Beverages were evaluated by 151 consumers on two occasions with or without
      priming statements. One priming statement declared "great flavor," the other
      priming statement declared 20 g protein per serving. A two way analysis of
      variance was applied to discern the role of each priming statement. The most
      important attribute for protein beverages was sweetener type, followed by amount
      of protein, followed by type of protein followed by label claim. Beverages with
      whey protein, naturally sweetened, reduced sugar and >=15 g protein per serving
      were most desired. Three consumer clusters were identified, differentiated by
      their preferences for protein type, sweetener and amount of protein. Priming
      statements positively impacted concept liking (P < 0.05) but had no effect on
      overall liking (P > 0.05). Consistent with trained panel profiles of increased
      cardboard flavor with higher protein content, consumers liked beverages with 10 g
      protein more than beverages with 20 g protein (6.8 compared with 5.7, P < 0.05).
      Protein beverages must have desirable flavor for wide consumer appeal. 

PMID- 25943858
TI  - Relations of vitamin D status, gender and type 2 diabetes in middle-aged
      Caucasians.

PMID- 25943859
TI  - Short-term cost analysis of complications related to glycated hemoglobin in
      patients with type 1 diabetes in the Italian setting.
AB  - AIMS: The aim of this study is to assess the impact of the diabetes-related
      complications on costs and to shed light on the potential savings that could be
      obtained by the National Healthcare System if better glycemic control was to be
      achieved in the type 1 diabetes population. METHODS: Epidemiologic data were used
      to distribute diabetes type 1 patients into A1c levels, and the relative risk of
      diabetes-related complications associated with the level of A1c was extrapolated
      from published risk curves. The costs associated with all complications in the
      Italian settings, retrieved from published literature, were used to estimate the
      economic impact of complications in each A1c level from the NHS perspective and
      the potential savings that could be obtained should a treatment strategy allow to
      achieve better metabolic control. RESULTS: The reduction in the number of
      complications translates into consistent monetary savings compared to current
      scenario. Within 5 years, ?29 and ?33 million would be saved if all patients
      reduced their A1c level by 1 % and within the range 7-8 % (53-64 mmol/mol),
      respectively. CONCLUSIONS: This work allows focusing on the impact of managing
      the diabetes-related complications on the overall costs, not yet reported in the
      literature. It was shown that the potential savings for the National Healthcare
      Service associated with a more effective glycemic control are substantial.

PMID- 25943860
TI  - Responses of parasitoids to volatiles induced by Chilo partellus oviposition on
      teosinte, a wild ancestor of maize.
AB  - Maize, a genetically diverse crop, is the domesticated descendent of its wild
      ancestor, teosinte. Recently, we have shown that certain maize landraces possess
      a valuable indirect defense trait not present in commercial hybrids. Plants of
      these landraces release herbivore-induced plant volatiles (HIPVs) that attract
      both egg [Trichogramma bournieri Pintureau & Babault (Hymenoptera:
      Trichogrammatidae)] and larval [Cotesia sesamiae Cameron (Hymenoptera:
      Braconidae)] parasitoids in response to stemborer egg deposition. In this study,
      we tested whether this trait also exists in the germplasm of wild Zea species.
      Headspace samples were collected from plants exposed to egg deposition by Chilo
      partellus Swinhoe (Lepidoptera: Crambidae) moths and unexposed control plants.
      Four-arm olfactometer bioassays with parasitic wasps, T. bournieri and C.
      sesamiae, indicated that both egg and larval parasitoids preferred HIPVs from
      plants with eggs in four of the five teosinte species sampled. Headspace samples
      from oviposited plants released higher amounts of EAG-active compounds such as
      (E)-4,8-dimethyl-1,3,7-nonatriene. In oviposition choice bioassays, plants
      without eggs were significantly preferred for subsequent oviposition by moths
      compared to plants with prior oviposition. These results suggest that this
      induced indirect defence trait is not limited to landraces but occurs in wild Zea
      species and appears to be an ancestral trait. Hence, these species possess a
      valuable trait that could be introgressed into domesticated maize lines to
      provide indirect defense mechanisms against stemborers.

PMID- 25943861
TI  - A Differential Role of Volatiles from Conspecific and Heterospecific Competitors
      in the Selection of Oviposition Sites by the Aphidophagous Hoverfly Sphaerophoria
      rueppellii.
AB  - The selection of oviposition sites by syrphids and other aphidophagous insects is
      influenced by the presence of con- and heterospecific competitors. Chemical cues
      play a role in this selection process, some of them being volatile
      semiochemicals. Yet, little is known about the identity and specificity of
      chemical signals that are involved in the searching behavior of these predators.
      In this study, we used olfactometer bioassays to explore the olfactory responses
      of gravid females and larvae of the syrphid Sphaerophoria rueppellii, focussing
      on volatiles from conspecific immature stages, as well as odors from immature
      stages of the competing coccinellid Adalia bipunctata. In addition, a multiple
      choice oviposition experiment was conducted to study if females respond
      differently when they can also sense their competitors through visual or tactile
      cues. Results showed that volatiles from plants and aphids did not affect the
      behavior of second-instars, whereas adult females strongly preferred odors from
      aphid colonies without competitors. Odors from conspecific immature stages had a
      repellent effect on S. rueppellii adult females, whereas their choices were not
      affected by volatiles coming from immature heterospecific A. bipunctata. The
      results imply that the syrphid uses odors to avoid sites that are already
      occupied by conspecifics. They did not avoid the odor of the heterospecific
      competitor, although in close vicinity they were found to avoid laying eggs on
      leaves that had traces of the coccinellid. Apparently adult syrphids do not rely
      greatly on volatile semiochemicals to detect the coccinellid, but rather use
      other stimuli at close range (e. g., visual or non-volatile compounds) to avoid
      this competitor. 

PMID- 25943862
TI  - Size Exclusion High Performance Liquid Chromatography: Re-Discovery of a Rapid
      and Versatile Method for Clean-Up and Fractionation in Chemical Ecology.
AB  - Solvent extraction of bioactive molecules from glands, tissues, or whole
      organisms is a common first step in chemoecological studies. Co-extraction of a
      surplus of high boiling materials such as triacylglycerides (TAGs) and other
      lipids with higher molecular weight might hamper the identification of volatile
      or medium-volatile semiochemicals by high resolution chromatographic and
      spectroscopic techniques. Therefore, effective clean-up procedures are needed to
      separate potential semiochemicals from the accompanying materials. Size exclusion
      high performance liquid chromatography (SE-HPLC), a technique often disregarded
      by chemoecologists, has proved to be a rapid and efficient clean-up method for
      complex crude extracts. We demonstrated that TAGs can be baseline separated from
      typical semiochemicals within less than 10 min on a porous gel stationary phase
      based on highly cross-linked polystyrene/divinylbenzene. We applied the method as
      a rapid one-step clean-up procedure for the analysis of juvenile hormone III in
      insect hemolymph by gas chromatography-mass spectrometry. We furthermore
      introduced some recent application examples on insect pheromones to demonstrate
      that SE-HPLC is not only an effective method for the purification of crude
      extracts, but can as well be used as a first fractionation step for the bioassay
      guided identification of behavior modifying natural products. SE-HPLC can be well
      operated with low-boiling solvents such as dichloromethane, and results in
      fraction volumes of typically less than one ml, which decreases the danger of
      losing volatile analytes during subsequent concentration steps.

PMID- 25943863
TI  - The Pap Test and Bethesda 2014: "The reports of my demise have been greatly
      exaggerated. (after a quotation from Mark Twain)".
AB  - The Bethesda System for gynecologic cytopathology has standardized reporting
      terminology over the past quarter of a century. In doing so, it has allowed for
      improved communication among practitioners around the world, facilitated large
      research projects and clinical trials, and has provided the basis from which
      uniformly accepted risk-based management strategies have been developed. Over
      time, changes in terminology and the underlying science require revisions, and
      the third edition of the Bethesda "Atlas" is the result of a yearlong effort to
      provide such an update. New material was developed and proposed via an Internet
      bulletin board, allowing for wide commentary that was compiled and incorporated.
      New images were collected, which comprised many new examples of equivocal
      presentations and mimics. New background material on the scientific basis
      supporting the terminology categories, the most current management algorithms,
      and comprehensive references were included. The effort completely refurbishes
      this standard reference that forms an inexpensive and, therefore, widely
      available resource for the world's cytology community. 

PMID- 25943864
TI  - Conservative Treatment Seems the Best Choice in Adenocarcinoma In Situ of the
      Cervix Uteri.
AB  - OBJECTIVE: To study diagnostic and therapeutic strategies, outcomes, and follow
      up in a large series of women with adenocarcinoma in situ (AIS) of the uterine
      cervix and investigate if human papillomavirus (HPV) typing among women with
      negative cytology reports would have helped with early AIS detection. MATERIALS
      AND METHODS: Records of 132 AIS cases diagnosed between 1989 and 2012 were
      retrieved. Clinical and pathological data were reviewed and analyzed. RESULTS:
      Mean age at diagnosis was 37 years. Seventy-two percent (n = 95) of all patients
      were asymptomatic; diagnosis was established using cytology and biopsy. Primary
      treatment for 124 patents was cold knife cone or loop electrosurgical excision
      procedure (LEEP). Positive margins were found in 18% of those women treated with
      CKC versus 40% in those treated with LEEP. The mean follow-up time was 62 months
      (range, 2-217 months; median, 46 months). Three recurrences were found after
      conservative treatment in 86 patients. High-risk HPV (hrHPV) positivity was
      detected in 115 (96%) of 120 patients, with HPV-18 being the most commonly
      occurring subtype (51%). CONCLUSIONS: There is a small risk of relapse after
      conservative therapy with cold knife cone or LEEP when resection margins are
      negative in women with AIS. Patients should be given the options of hysterectomy
      or conservative therapy with strict follow-up.

PMID- 25943865
TI  - The Impact of Accessible Cervical Cancer Screening in Peru-The Dia del Mercado
      Project.
AB  - OBJECTIVE: The purpose of this study was to determine the potential impact of
      accessible secondary cervical cancer prevention efforts in indigenous Peruvian
      women living in the rural Andes Mountain region of Peru. METHODS: Peruvian women
      presenting for a Pap test or visiting a local marketplace, clinic, or public
      facility were asked to complete a questionnaire that assessed their response to
      the rural Pap screening program. We identified the following: 1) barriers to
      care, 2) patient knowledge of cervical cancer and Pap tests, and 3) perceptions
      of and reactions to the market clinic model. Chi-square or Fisher exact tests, t
      tests and 1-way ANOVA were used to examine differences between locations.
      RESULTS: Of 4,560 women enrolled, those examined in tents indicated it was easier
      to get a Pap test (98.7%, P = 0.001) compared with women seen in buildings
      (96.8%) or CerviCusco (98.0%), and they felt it was more important to have a Pap
      test close to their home more often (99.3%) than those seen at CerviCusco (97.8%)
      or buildings (98.8%). Women examined in tents felt the market was a good place to
      have a Pap test more often (67.0%, P < 0.001) than women who went to buildings
      (46.0%) or CerviCusco (29.2%). CONCLUSIONS: Many poor indigenous women living in
      isolated regions are unable to travel to distant health-care facilities. Using a
      novel mobile clinic model, the "Dia del Mercado Project" successfully reduced
      barriers to cervical cancer screening by using local marketplaces.

PMID- 25943866
TI  - A Review of Lesions of the Posterior Fourchette, Posterior Vestibule (Fossa
      Navicularis), and Hymen.
AB  - Lesions specific to the posterior fourchette, posterior vestibule (fossa
      navicularis), and hymen are reviewed. Knowledge of these regional lesions will be
      helpful if such a patient is encountered. 

PMID- 25943867
TI  - Polarized Light Colposcopy Compared With Standard Colposcopy.
AB  - OBJECTIVE: The objective of this study was to determine the potential benefits of
      polarized light colposcopy compared with standard colposcopy examinations in the
      evaluation of women with abnormal cervical cytology. MATERIALS AND METHODS:
      Polarized and standard colposcopy examinations were performed on 330 subjects.
      Respective images and biopsy annotations were obtained. Sensitivity and
      specificity; differences in the severity of cervical neoplasia; agreement of
      colposcopy impression, biopsy intent, and biopsy site; and differences in the
      number of biopsies were determined using the ROC, Bowker's test of symmetry,
      kappa statistic, and paired t test, respectively. RESULTS: The sensitivity and
      specificity for a lesion being seen with nonpolarized light and polarized light
      colposcopy were 96.8% and 64.5%, and 96.8% and 64.9%, respectively. There was no
      statistically significant difference in the ROC of the lesion being seen between
      nonpolarized (80.7) and polarized (80.9) colposcopy. Likewise, there was no
      statistically significant difference in the ROC of intent to biopsy between
      nonpolarized (80.2) and polarized colposcopy (78.8). The agreement of cervical
      histopathology and colposcopy impression for nonpolarized and polarized
      colposcopy were 0.986 and 0.952, respectively. There was no significant
      difference between nonpolarized and polarized colposcopy in the mean number of
      lesions seen or number of sites intended to biopsy. CONCLUSIONS: Polarized light
      colposcopy was not useful as an adjunct to conventional colposcopy in this study.
      Further research needs to be performed to determine the overall utility of
      polarized light colposcopy in clinical practice.

PMID- 25943868
TI  - Differential regulation of urine proteins in urothelial neoplasm.
AB  - Urothelial neoplasm of the urinary bladder has a high rate of multifocality and
      recurrence. To understand this we first need to understand the changes in the
      molecular level that distinguishes a normal individual from a patient and also a
      low grade neoplasm from a high grade. In this work we aim to study the urine
      proteome of Indian patients with urothelial neoplasm categorised on the basis of
      their p53 immunohistochemistry. The urine samples of pre-operative patients were
      subjected to two dimensional gel electrophoresis followed by densitometric
      analysis and spot identification using MALDI mass spectrometry. Our study shows
      that few proteins such as albumin, alpha 1 antitrypsin, apolipoprotein A1,
      transferrin, transthyretin, haptoglobin and haemoglobin beta chain were
      upregulated and inter alpha trypsin inhibitor heavy chain was downregulated in
      the disease samples. Further we have reported that some of these proteins show an
      association with disease severity. The present study marks the first step in the
      identification of new diagnostic markers as well as therapeutic targets.
      BIOLOGICAL SIGNIFICANCE: Bladder carcinoma is the ninth most common cancer
      worldwide. It has gained attention within both clinicians and cancer biologists
      because of its recurrence and mortality rate. Identifying the prognostic factors
      of progression is a challenge, so that high risk patients who may be a candidate
      for a radical cystectomy may be identified. In this study we have attempted to
      study the changes observed in the urinary protein levels of urothelial neoplasm
      patients. The samples were graded based on p53 immunohistochemistry staining. We
      have reported eight (8) proteins, mostly highly abundant; those have exhibited
      differential regulation in case of diseased samples. This study is first of its
      kind that associates the changes in the urinary protein levels to that of the
      severity of the disease. We believe that the findings can be used as a stepping
      stone in the development of a noninvasive prognostic tool for the disease. This
      article is part of a Special Issue entitled: Proteomics in India.

PMID- 25943869
TI  - Metabolomics and its integration with systems biology: PSI 2014 conference panel
      discussion report.
AB  - Metabolomics, being a relatively new field, is facing multiple challenges related
      to data acquisition and interpretation, reproducibility across analytical
      platforms, integration with other omics approaches and translation into
      theragnostic biomarkers. There is an immediate need to overcome these challenges
      in order to make metabolomics more useful and reliable in terms of improving our
      current understanding of disease biology and help in developing predictive
      biomarkers. Researchers interested in metabolomics gathered for a panel
      discussion on 'Metabolomics and its integration with systems biology' during the
      6th Annual Meeting of Proteomics Society-India and International Conference on
      "Proteomics from Discovery to Function" held at the Indian Institute of
      Technology, Bombay from December 7-9, 2014. The panel discussed various
      challenges related to metabolomics and also proposed several effective solutions
      for optimum implementation of metabolomics in clinical practice. The key areas of
      panel discussion were improvement in metabolite databases with comprehensive
      spectral libraries, need for extensive bioinformatics tools for integrative
      approaches and serious considerations for clinical validation of the biomarkers
      for the successful implementation of metabolomics in clinics. BIOLOGICAL
      SIGNIFICANCE: Information drafted in this report is significant for researchers
      working in metabolomics field to overcome the challenges and successful
      implementation of metabolomics in clinical practice. This article is part of a
      special issue titled: Proteomics in India.

PMID- 25943870
TI  - A scoping review of the association between rural medical education and rural
      practice location.
AB  - BACKGROUND: Inequitable distribution of the medical workforce is an international
      problem that undermines universal access to healthcare. Governments in many
      countries have invested in rural-focused medical education programs to increase
      the supply of rural doctors. METHODS: Using a structured five-step approach, a
      scoping review was conducted to map the existing evidence on the relationship
      between professional entry-level, pre-vocational medical education delivered in
      rural settings and rural workforce outcomes. Key search terms were developed,
      with database searches yielding 37 relevant articles. During data charting, a set
      of types of studies emerged, and we developed a typology to assist with article
      sorting and information structuring. RESULTS: Medical students attending a rural
      campus or spending time in a rural area are more likely to practise in non
      metropolitan areas upon graduation than students studying at a city campus. In
      many cases, these positive findings could be confounded by students having a
      rural origin or being predisposed to want rural work. There is some evidence to
      suggest that the longer a person spends time as a medical student in a rural
      area, the more likely they are to work rurally following graduation. Overall, the
      articles located had limitations related to small sample size, inconsistent
      definition of rurality and lack of attention to controlling for variables that
      might influence rural practice decision, for example, rural background.
      Comparative data were lacking, and most studies were conducted by staff from the
      medical schools that were the focus of the research. There was no consideration
      given in any study found to the cost-effectiveness of entry-level medical
      education delivered in rural settings versus other ways of producing rural
      practitioners. CONCLUSIONS: Given limitations, available evidence suggests that
      medical education in a rural location does increase the number of medical
      graduates that will work in a rural place. There are indications of a gradient
      effect where increased rural practice exposure during medical education leads to
      more rurally located graduates; however, robust studies are needed to verify this
      finding. Given the significant funding being directed to universities to increase
      graduates that will work rurally, appropriate future research is recommended.

PMID- 25943871
TI  - Brainstem cavernous malformations.
AB  - Of all cavernous malformations (CMs), 4% to 35% are found in the brainstem
      accounting for 13% of vascular malformations of the posterior fossa. The annual
      risk of hemorrhage associated with a CM with no history of a previous hemorrhagic
      episode is very low ranging from 0.6% to 1.1% per year. However, the risk of
      recurrent hemorrhage after a presenting bleed is significantly higher. There is a
      correlation between the extent of persistent neurological deficits and the number
      of recurrent hemorrhages as rehemorrhage increases the rate and severity of
      neurological deficits. Neurological deficits often improve after a hemorrhagic
      event spontaneously and sometimes resolve completely. The indication for surgery
      in patients with brainstem CMs is controversial. Over the years, we have taken a
      more cautious stance and we often recommend observation in patients after a
      single symptomatic bleed as most patients return to a good level of functioning
      after a single bleed. Surgery is recommended for more aggressive lesions usually
      after a recurrent bleed. In general, given the very low risk of bleeding from
      truly asymptomatic lesions, surgery should not be considered in these patients.
      For symptomatic lesions which have presented with hemorrhage, the decision of
      whether or not to proceed with surgical resection is related to the risk of
      surgery, patient's disposition and perceived risk of rebleeding. Favorable
      outcome can be achieved through surgical resection after an appropriate selection
      of the patients and thorough preoperative surgical planning. 

PMID- 25943873
TI  - When is the burden of responsibility over for the surgeon?

PMID- 25943872
TI  - Altered expression of caspases-4 and -5 during inflammatory bowel disease and
      colorectal cancer: Diagnostic and therapeutic potential.
AB  - Caspases are a group of proteolytic enzymes involved in the co-ordination of
      cellular processes, including cellular homeostasis, inflammation and apoptosis.
      Altered activity of caspases, particularly caspase-1, has been implicated in the
      development of intestinal diseases, such as inflammatory bowel disease (IBD) and
      colorectal cancer (CRC). However, the involvement of two related inflammatory
      caspase members, caspases-4 and -5, during intestinal homeostasis and disease has
      not yet been established. This study demonstrates that caspases-4 and -5 are
      involved in IBD-associated intestinal inflammation. Furthermore, we found a clear
      correlation between stromal caspase-4 and -5 expression levels, inflammation and
      disease activity in ulcerative colitis patients. Deregulated intestinal
      inflammation in IBD patients is associated with an increased risk of developing
      CRC. We found robust expression of caspases-4 and -5 within intestinal epithelial
      cells, exclusively within neoplastic tissue, of colorectal tumours. An
      examination of adjacent normal, inflamed and tumour tissue from patients with
      colitis-associated CRC confirmed that stromal expression of caspases-4 and -5 is
      increased in inflamed and dysplastic tissue, while epithelial expression is
      restricted to neoplastic tissue. In addition to identifying caspases-4 and -5 as
      potential targets for limiting intestinal inflammation, this study has identified
      epithelial-expressed caspases-4 and -5 as biomarkers with diagnostic and
      therapeutic potential in CRC. 

PMID- 25943875
TI  - Fontan conversion: guidelines from Down Under.

PMID- 25943874
TI  - Prolonged pericardial drainage using a soft drain reduces pericardial effusion
      and need for additional pericardial drainage following orthotopic heart
      transplantation.
AB  - OBJECTIVES: Pericardial effusion can cause haemodynamic compromise after heart
      transplantation. We identified the effects of soft drains on the development of
      pericardial effusion. METHODS: We enrolled 250 patients >=17 years of age who
      underwent heart transplantation between July 1999 and April 2012 and received two
      conventional tubes (n = 96; 32 French), or two tubes with a soft drain (n = 154;
      4.8 mm wide). The development of significant pericardial effusion or the need for
      drainage procedure during 1 month after heart transplantation was compared with
      the use of the propensity score matching method to adjust for selection bias.
      RESULTS: At 1 month after transplantation, 69 patients (27.6%) developed
      significant pericardial effusion. Among these, 13 patients (5.2%) underwent
      pericardial drainage. According to multivariate analysis, history of previous
      cardiac surgery [odds ratio (OR) = 0.162; 95% confidence interval (CI) = 0.046
      0.565; P = 0.004] and placement of a soft drain (OR = 0.186; 95% CI = 0.100
      0.346; P < 0.001) were significant factors that prevented pericardial effusion or
      the need for drainage during the early postoperative period. For the 82
      propensity score matched pairs, patients receiving an additional soft drain were
      at a lower risk of the development of significant pericardial effusion or the
      need for a pericardial drainage procedure during 1 month (OR = 0.148; 95% CI =
      0.068-0.318; P < 0.001) compared with those receiving only two conventional
      tubes. CONCLUSIONS: Pericardial soft drainage is a simple and safe procedure that
      reduces pericardial effusion and decreases the need for pericardial drainage
      after heart transplantation.

PMID- 25943876
TI  - A giant congenital aneurysm of the left atrium.

PMID- 25943878
TI  - Jeronimo Perez Ortiz's 1886 Album of Clinical Dermatology.

PMID- 25943877
TI  - Drug Redeployment to Kill Leukemia and Lymphoma Cells by Disrupting SCD1-Mediated
      Synthesis of Monounsaturated Fatty Acids.
AB  - The redeployed drug combination of bezafibrate and medroxyprogesterone acetate
      (designated BaP) has potent in vivo anticancer activity in acute myelogenous
      leukemia (AML) and endemic Burkitt lymphoma (eBL) patients; however, its
      mechanism-of-action is unclear. Given that elevated fatty acid biosynthesis is a
      hallmark of many cancers and that these drugs can affect lipid metabolism, we
      hypothesized that BaP exerts anticancer effects by disrupting lipogenesis. We
      applied mass spectrometry-based lipidomics and gene and protein expression
      measurements of key lipogenic enzymes [acetyl CoA carboxylase 1 (ACC1), fatty
      acid synthase (FASN), and stearoyl CoA desaturase 1 (SCD1)] to AML and eBL cell
      lines treated with BaP. BaP treatment decreased fatty acid and phospholipid
      biosynthesis from (13)C D-glucose. The proportion of phospholipid species with
      saturated and monounsaturated acyl chains was also decreased after treatment,
      whereas those with polyunsaturated chains increased. BaP decreased SCD1 protein
      levels in each cell line (0.46- to 0.62-fold; P < 0.023) and decreased FASN
      protein levels across all cell lines (0.87-fold decrease; P = 1.7 * 10(-4)).
      Changes to ACC1 protein levels were mostly insignificant. Supplementation with
      the SCD1 enzymatic product, oleate, rescued AML and e-BL cells from BaP cell
      killing and decreased levels of BaP-induced reactive oxygen species, whereas
      supplementation with the SCD1 substrate (and FASN product), palmitate, did not
      rescue cells. In conclusion, these data suggest that the critical anticancer
      actions of BaP are decreases in SCD1 levels and monounsaturated fatty acid
      synthesis. To our knowledge, this is the first time that clinically available
      antileukemic and antilymphoma drugs targeting SCD1 have been reported.

PMID- 25943879
TI  - Crystallization speed of salbutamol as a function of relative humidity and
      temperature.
AB  - Spray dried salbutamol sulphate and salbutamol base particles are amorphous as a
      result of spray drying. As there is always the risk of recrystallization of
      amorphous material, the aim of this work is the evaluation of the temperature and
      humidity dependent recrystallization of spray dried salbutamol sulphate and base.
      Therefore in-situ Powder X-ray Diffraction (PXRD) studies of the crystallization
      process at various temperature (25 and 35  degrees C) and humidity (60%, 70%,
      80%, 90% relative humidity) conditions were performed. It was shown that the
      crystallization speed of salbutamol sulphate and base is a non-linear function of
      both temperature and relative humidity. The higher the relative humidity the
      higher is the crystallization speed. At 60% relative humidity salbutamol base as
      well as salbutamol sulphate were found to be amorphous even after 12 h, however
      samples changed optically. At 70% and 90% RH recrystallization of salbutamol base
      is completed after 3 h and 30 min and recrystallization of salbutamol sulphate
      after 4h and 1h, respectively. Higher temperature (35  degrees C) also leads to
      increased crystallization speeds at all tested values of relative humidity.

PMID- 25943880
TI  - Development of a new approach to investigating the drug transfer from colloidal
      carrier systems applying lipid nanosuspension-containing alginate microbeads as
      acceptor.
AB  - As a new approach to analyzing the release behavior of lipophilic drugs from
      colloidal carriers, solid trimyristin nanoparticles were incorporated into
      differently sized (34-1363 MUm) calcium alginate hydrogel microbeads to serve as
      acceptor in release studies. The microbeads were prepared by electrostatic
      droplet generation or by a spraying method. Trimyristin nanoemulsion samples
      loaded with the fluorescent drug model Nile red were mixed with the nanoparticle
      containing microbeads to perform transfer studies. As a result of a rather large
      diffusion barrier a slow transfer (24-57 min) was observed using large acceptor
      beads (~330-1360 MUm). In contrast, Nile red transferred quickly (~1.4 min) into
      smaller microbeads (<50 MUm). This new experimental approach applying
      nanoparticle-containing hydrogel particles with a size below 50 MUm as acceptor
      systems is a promising technique to investigate the release of lipophilic
      substances from lipid nanoparticles under close to realistic conditions. However,
      there is still room for technical improvement, e.g., with regard to the water
      loss from microbeads that was observed during sampling by centrifugation and
      filtration (required to separate the small sized alginate particles) which is
      expected to have had some effect on the dye content determined during these
      experiments.

PMID- 25943881
TI  - Compulsory drug detention exposure is associated with not receiving
      antiretroviral treatment among people who inject drugs in Bangkok, Thailand: a
      cross-sectional study.
AB  - BACKGROUND: Thailand has experienced a longstanding epidemic of HIV among people
      who inject drugs (PWID). However, antiretroviral treatment (ART) coverage among
      HIV-positive PWID has historically remained low. While ongoing drug law
      enforcement involving periodic police crackdowns is known to increase the risk of
      HIV transmission among Thai PWID, the impact of such drug policy approaches on
      the ART uptake has been understudied. Therefore, we sought to identify factors
      associated with not receiving ART among HIV-positive PWID in Bangkok, Thailand,
      with a focus on factors pertaining to drug law enforcement. METHODS: Data were
      collected from a community-recruited sample of HIV-positive PWID in Bangkok who
      participated in the Mitsampan Community Research Project between June 2009 and
      October 2011. We identified factors associated with not receiving ART at the time
      of interview using multivariate logistic regression. RESULTS: In total, 128 HIV
      positive PWID participated in this study, with 58 (45.3%) reporting not receiving
      ART at the time of interview. In multivariate analyses, completing less than
      secondary education (adjusted odds ratio [AOR]: 3.32 ; 95% confidence interval
      [CI]: 1.48 - 7.45), daily midazolam injection (AOR: 3.22, 95% CI: 1.45 - 7.15)
      and exposure to compulsory drug detention (AOR: 3.36, 95% CI: 1.01 - 11.21) were
      independently and positively associated with not receiving ART. Accessing peer
      based healthcare information or support services was independently and positively
      associated with receiving ART (AOR: 0.21, 95% CI: 0.05 - 0.84). CONCLUSIONS:
      Approximately half of our study group of HIV-positive PWID reported not receiving
      ART at the time of interview. Daily midazolam injectors, those with lower
      education attainment, and individuals who had been in compulsory drug detention
      were more likely to be non-recipients of ART whereas those who accessed peer
      based healthcare-related services were more likely to receive ART. These findings
      suggest a potentially adverse impact of compulsory drug detention and highlight
      the need to expand interventions to facilitate access to ART among HIV-positive
      PWID in this setting.

PMID- 25943882
TI  - Lowering the quantification limit of the QubitTM RNA HS assay using RNA spike-in.
AB  - BACKGROUND: RNA quantification is often a prerequisite for most RNA analyses such
      as RNA sequencing. However, the relatively low sensitivity and large sample
      consumption of traditional RNA quantification methods such as UV
      spectrophotometry and even the much more sensitive fluorescence-based RNA
      quantification assays, such as the QubitTM RNA HS Assay, are often inadequate for
      measuring minute levels of RNA isolated from limited cell and tissue samples and
      biofluids. Thus, there is a pressing need for a more sensitive method to reliably
      and robustly detect trace levels of RNA without interference from DNA. METHODS:
      To improve the quantification limit of the QubitTM RNA HS Assay, we spiked-in a
      known quantity of RNA to achieve the minimum reading required by the assay.
      Samples containing trace amounts of RNA were then added to the spike-in and
      measured as a reading increase over RNA spike-in baseline. We determined the
      accuracy and precision of reading increases between 1 and 20 pg/MUL as well as
      RNA-specificity in this range, and compared to those of RiboGreen((r)), another
      sensitive fluorescence-based RNA quantification assay. We then applied QubitTM
      Assay with RNA spike-in to quantify plasma RNA samples. RESULTS: RNA spike-in
      improved the quantification limit of the QubitTM RNA HS Assay 5-fold, from 25
      pg/MUL down to 5 pg/MUL while maintaining high specificity to RNA. This enabled
      quantification of RNA with original concentration as low as 55.6 pg/MUL compared
      to 250 pg/MUL for the standard assay and decreased sample consumption from 5 to 1
      ng. Plasma RNA samples that were not measurable by the QubitTM RNA HS Assay were
      measurable by our modified method. CONCLUSIONS: The QubitTM RNA HS Assay with RNA
      spike-in is able to quantify RNA with high specificity at 5-fold lower
      concentration and uses 5-fold less sample quantity than the standard QubitTM
      Assay.

PMID- 25943883
TI  - Causes and consequences of coagulation activation in sepsis: an evolutionary
      medicine perspective.
AB  - BACKGROUND: Coagulation and innate immunity have been linked together for at
      least 450 million years of evolution. Sepsis, one of the world's leading causes
      of death, is probably the condition in which this evolutionary link is more
      evident. However, the biological and the clinical relevance of this association
      have only recently gained the attention of the scientific community. DISCUSSION:
      During sepsis, the host response to a pathogen is invariably associated with
      coagulation activation. For several years, coagulation activation has been solely
      regarded as a mechanism of tissue damage, a concept that led to several clinical
      trials of anticoagulant agents for sepsis. More recently, this paradigm has been
      challenged by the failure of these clinical trials, and by a growing bulk of
      evidence supporting the concept that coagulation activation is beneficial for
      pathogen clearance. In this article we discuss recent basic and clinical data
      that point to a more balanced view of the detrimental and beneficial consequences
      of coagulation activation in sepsis. Reappraisal of the association between
      coagulation and immune activation from an evolutionary medicine perspective
      offers a unique opportunity to gain new insights about the pathogenesis of
      sepsis, paving the way to more successful approaches in both basic and clinical
      research in this field.

PMID- 25943884
TI  - Induction of autophagy in rats upon overexpression of wild-type and mutant
      optineurin gene.
AB  - BACKGROUND: Optineurin is a gene associated with normal tension glaucoma and
      amyotrophic lateral sclerosis. It has been reported previously that in cultured
      RGC5 cells, the turnover of endogenous optineurin involves mainly the ubiquitin
      proteasome pathway (UPP). When optineurin is upregulated or mutated, the UPP
      function is compromised as evidenced by a decreased proteasome beta5 subunit
      (PSMB5) level and autophagy is induced for clearance of the optineurin protein.
      RESULTS: Adeno-associated type 2 viral (AAV2) vectors for green fluorescence
      protein (GFP) only, GFP-tagged wild-type and Glu50Lys (E50K) mutated optineurin
      were intravitreally injected into rats for expression in retinal ganglion cells
      (RGCs). Following intravitreal injections, eyes that received optineurin vectors
      exhibited retinal thinning, as well as RGC and axonal loss compared to GFP
      controls. By immunostaining and Western blotting, the level of PSMB5 and
      autophagic substrate degradation marker p62 was reduced, and the level of
      autophagic marker microtubule associated protein 1 light chain 3 (LC3) was
      enhanced. The UPP impairment and autophagy induction evidently occurred in vivo
      as in vitro. The optineurin level, RGC and axonal counts, and apoptosis in AAV2
      E50K-GFP-injected rat eyes were averted to closer to normal limits after
      treatment with rapamycin, an autophagic enhancer. CONCLUSIONS: The UPP function
      was reduced and autophagy was induced when wild-type and E50K optineurin was
      overexpressed in rat eyes. This study validates the in vitro findings, confirming
      that UPP impairment and autophagy induction also occur in vivo. In addition,
      rapamycin is demonstrated to clear the accumulated mutant optineurin. This agent
      may potentially be useful for rescuing of the adverse optineurin phenotypes in
      vivo.

PMID- 25943886
TI  - Non-steroidal anti-inflammatory drug indometacin enhances endogenous
      remyelination.
AB  - Multiple sclerosis is the most frequent demyelinating disease in the CNS that is
      characterized by inflammatory demyelinating lesions and axonal loss, the
      morphological correlate of permanent clinical disability. Remyelination does
      occur, but is limited especially in chronic disease stages. Despite effective
      immunomodulatory therapies that reduce the number of relapses the progressive
      disease phase cannot be prevented. Therefore, promotion of neuroprotective and
      repair mechanisms, such as remyelination, represents an attractive additional
      treatment strategy. A number of pathways have been identified that may contribute
      to impaired remyelination in MS lesions, among them the Wnt/beta-catenin pathway.
      Here, we demonstrate that indometacin, a non-steroidal anti-inflammatory drug
      (NSAID) that has been also shown to modulate the Wnt/beta-catenin pathway in
      colorectal cancer cells promotes differentiation of primary human and murine
      oligodendrocytes, myelination of cerebellar slice cultures and remyelination in
      cuprizone-induced demyelination. Our in vitro experiments using GSK3beta
      inhibitors, luciferase reporter assays and oligodendrocytes expressing a mutant,
      dominant stable beta-catenin indicate that the mechanism of action of indometacin
      depends on GSK3beta activity and beta-catenin phosphorylation. Indometacin might
      represent a promising treatment option to enhance endogenous remyelination in MS
      patients. 

PMID- 25943888
TI  - Glioblastoma: pathology, molecular mechanisms and markers.
AB  - Recent advances in genomic technology have led to a better understanding of key
      molecular alterations that underlie glioblastoma (GBM). The current WHO-based
      classification of GBM is mainly based on histologic features of the tumor, which
      frequently do not reflect the molecular differences that describe the diversity
      in the biology of these lesions. The current WHO definition of GBM relies on the
      presence of high-grade astrocytic neoplasm with the presence of either
      microvascular proliferation and/or tumor necrosis. High-throughput analyses have
      identified molecular subtypes and have led to progress in more accurate
      classification of GBM. These findings, in turn, would result in development of
      more effective patient stratification, targeted therapeutics, and prediction of
      patient outcome. While consensus has not been reached on the precise nature and
      means to sub-classify GBM, it is clear that IDH-mutant GBMs are clearly distinct
      from GBMs without IDH1/2 mutation with respect to molecular and clinical
      features, including prognosis. In addition, recent findings in pediatric GBMs
      regarding mutations in the histone H3F3A gene suggest that these tumors may
      represent a 3rd major category of GBM, separate from adult primary (IDH1/2 wt),
      and secondary (IDH1/2 mut) GBMs. In this review, we describe major clinically
      relevant genetic and epigenetic abnormalities in GBM-such as mutations in IDH1/2,
      EGFR, PDGFRA, and NF1 genes-altered methylation of MGMT gene promoter, and
      mutations in hTERT promoter. These markers may be incorporated into a more
      refined classification system and applied in more accurate clinical decision
      making process. In addition, we focus on current understanding of the biologic
      heterogeneity and classification of GBM and highlight some of the molecular
      signatures and alterations that characterize GBMs as histologically defined. We
      raise the question whether IDH-wild type high grade astrocytomas without
      microvascular proliferation or necrosis might best be classified as GBM, even if
      they lack the histologic hallmarks as required in the current WHO classification.
      Alternatively, an astrocytic tumor that fits the current histologic definition of
      GBM, but which shows an IDH mutation may in fact be better classified as a
      distinct entity, given that IDH-mutant GBM are quite distinct from a biological
      and clinical perspective. 

PMID- 25943887
TI  - Antisense RNA foci in the motor neurons of C9ORF72-ALS patients are associated
      with TDP-43 proteinopathy.
AB  - GGGGCC repeat expansions of C9ORF72 represent the most common genetic variant of
      amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. We and others
      have proposed that RNA transcribed from the repeat sequence is toxic via
      sequestration of RNA-binding factors. Both GGGGCC-repeat (sense) and CCCCGG
      repeat (antisense) molecules are detectable by fluorescence in situ hybridisation
      as RNA foci, but their relative expression pattern within the CNS and
      contribution to disease has not been determined. Blinded examination of CNS
      biosamples from ALS patients with a repeat expansion of C9ORF72 showed that
      antisense foci are present at a significantly higher frequency in cerebellar
      Purkinje neurons and motor neurons, whereas sense foci are present at a
      significantly higher frequency in cerebellar granule neurons. Consistent with
      this, inclusions containing sense or antisense derived dipeptide repeat proteins
      were present at significantly higher frequency in cerebellar granule neurons or
      motor neurons, respectively. Immunohistochemistry and UV-crosslinking studies
      showed that sense and antisense RNA molecules share similar interactions with
      SRSF2, hnRNP K, hnRNP A1, ALYREF, and hnRNP H/F. Together these data suggest
      that, although sense and antisense RNA molecules might be expected to be equally
      toxic via their shared protein binding partners, distinct patterns of expression
      in various CNS neuronal populations could lead to relative differences in their
      contribution to the pathogenesis of neuronal injury. Moreover in motor neurons,
      which are the primary target of pathology in ALS, the presence of antisense foci
      (chi (2), p < 0.00001) but not sense foci (chi (2), p = 0.75) correlated with
      mislocalisation of TDP-43, which is the hallmark of ALS neurodegeneration. This
      has implications for translational approaches to C9ORF72 disease, and furthermore
      interacting RNA-processing factors and transcriptional activators responsible for
      antisense versus sense transcription might represent novel therapeutic targets. 

PMID- 25943885
TI  - Oligodendroglioma: pathology, molecular mechanisms and markers.
AB  - For nearly a century, the diagnosis and grading of oligodendrogliomas and
      oligoastrocytomas has been based on histopathology alone. Roughly 20 years ago,
      the first glioma-associated molecular signature was found with complete
      chromosome 1p and 19q codeletion being particularly common in histologically
      classic oligodendrogliomas. Subsequently, this codeletion appeared to not only
      carry diagnostic, but also prognostic and predictive information, the latter
      aspect only recently resolved after carefully constructed clinical trials with
      very long follow-up times. More recently described biomarkers, including the non
      balanced translocation leading to 1p/19q codeletion, promoter hypermethylation of
      the MGMT gene, mutations of the IDH1 or IDH2 gene, and mutations of FUBP1 (on 1p)
      or CIC (on 19q), have greatly enhanced our understanding of oligodendroglioma
      biology, although their diagnostic, prognostic, and predictive roles are less
      clear. It has therefore been suggested that complete 1p/19q codeletion be
      required for the diagnosis of 'canonical oligodendroglioma'. This transition to
      an integrated morphological and molecular diagnosis may result in the
      disappearance of oligoastrocytoma as an entity, but brings new challenges as
      well. For instance it needs to be sorted out how (histopathological) criteria for
      grading of 'canonical oligodendrogliomas' should be adapted, how pediatric
      oligodendrogliomas (known to lack codeletions) should be defined, which platforms
      and cut-off levels should ideally be used for demonstration of particular
      molecular aberrations, and how the diagnosis of oligodendroglioma should be made
      in centers/countries where molecular diagnostics is not available. Meanwhile,
      smart integration of morphological and molecular information will lead to
      recognition of biologically much more uniform groups within the spectrum of
      diffuse gliomas and thereby facilitate tailored treatments for individual
      patients.

PMID- 25943889
TI  - Beta-amyloid deposition in chronic traumatic encephalopathy.
AB  - Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated
      with repetitive mild traumatic brain injury. It is defined pathologically by the
      abnormal accumulation of tau in a unique pattern that is distinct from other
      tauopathies, including Alzheimer's disease (AD). Although trauma has been
      suggested to increase amyloid beta peptide (Abeta) levels, the extent of Abeta
      deposition in CTE has not been thoroughly characterized. We studied a
      heterogeneous cohort of deceased athletes and military veterans with
      neuropathologically diagnosed CTE (n = 114, mean age at death = 60) to test the
      hypothesis that Abeta deposition is altered in CTE and associated with more
      severe pathology and worse clinical outcomes. We found that Abeta deposition,
      either as diffuse or neuritic plaques, was present in 52 % of CTE subjects.
      Moreover, Abeta deposition in CTE occurred at an accelerated rate and with
      altered dynamics in CTE compared to a normal aging population (OR = 3.8, p <
      0.001). We also found a clear pathological and clinical dichotomy between those
      CTE cases with Abeta plaques and those without. Abeta deposition was
      significantly associated with the presence of the APOE epsilon4 allele (p =
      0.035), older age at symptom onset (p < 0.001), and older age at death (p <
      0.001). In addition, when controlling for age, neuritic plaques were
      significantly associated with increased CTE tauopathy stage (beta = 2.43, p =
      0.018), co-morbid Lewy body disease (OR = 5.01, p = 0.009), and dementia (OR =
      4.45, p = 0.012). A subset of subjects met the diagnostic criteria for both CTE
      and AD, and in these subjects both Abeta plaques and total levels of Abeta1-40
      were increased at the depths of the cortical sulcus compared to the gyral crests.
      Overall, these findings suggest that Abeta deposition is altered and accelerated
      in a cohort of CTE subjects compared to normal aging and that Abeta is associated
      with both pathological and clinical progression of CTE independent of age.

PMID- 25943890
TI  - Whole-genome sequencing reveals important role for TBK1 and OPTN mutations in
      frontotemporal lobar degeneration without motor neuron disease.
AB  - Frontotemporal lobar degeneration with TAR DNA-binding protein 43 inclusions
      (FTLD-TDP) is the most common pathology associated with frontotemporal dementia
      (FTD). Repeat expansions in chromosome 9 open reading frame 72 (C9ORF72) and
      mutations in progranulin (GRN) are the major known genetic causes of FTLD-TDP;
      however, the genetic etiology in the majority of FTLD-TDP remains unexplained. In
      this study, we performed whole-genome sequencing in 104 pathologically confirmed
      FTLD-TDP patients from the Mayo Clinic brain bank negative for C9ORF72 and GRN
      mutations and report on the contribution of rare single nucleotide and copy
      number variants in 21 known neurodegenerative disease genes. Interestingly, we
      identified 5 patients (4.8 %) with variants in optineurin (OPTN) and TANK-binding
      kinase 1 (TBK1) that are predicted to be highly pathogenic, including two double
      mutants. Case A was a compound heterozygote for mutations in OPTN, carrying the
      p.Q235* nonsense and p.A481V missense mutation in trans, while case B carried a
      deletion of OPTN exons 13-15 (p.Gly538Glufs*27) and a loss-of-function mutation
      (p.Arg117*) in TBK1. Cases C-E carried heterozygous missense mutations in TBK1,
      including the p.Glu696Lys mutation which was previously reported in two
      amyotrophic lateral sclerosis (ALS) patients and is located in the OPTN binding
      domain. Quantitative mRNA expression and protein analysis in cerebellar tissue
      showed a striking reduction of OPTN and/or TBK1 expression in 4 out of 5 patients
      supporting pathogenicity in these specific patients and suggesting a loss-of
      function disease mechanism. Importantly, neuropathologic examination showed FTLD
      TDP type A in the absence of motor neuron disease in 3 pathogenic mutation
      carriers. In conclusion, we highlight TBK1 as an important cause of pure FTLD
      TDP, identify the first OPTN mutations in FTLD-TDP, and suggest a potential
      oligogenic basis for at least a subset of FTLD-TDP patients. Our data further add
      to the growing body of evidence linking ALS and FTD and suggest a key role for
      the OPTN/TBK1 pathway in these diseases. 

PMID- 25943892
TI  - Achilles tendon structure improves on UTC imaging over a 5-month pre-season in
      elite Australian football players.
AB  - Pre-season injuries are common and may be due to a reintroduction of training
      loads. Tendons are sensitive to changes in load, making them vulnerable to injury
      in the pre-season. This study investigated changes in Achilles tendon structure
      on ultrasound tissue characterization (UTC) over the course of a 5-month pre
      season in elite male Australian football players. Eighteen elite male Australian
      football players with no history of Achilles tendinopathy and normal Achilles
      tendons were recruited. The left Achilles tendon was scanned with UTC to quantify
      the stability of the echopattern. Participants were scanned at the start and
      completion of a 5-month pre-season. Fifteen players remained asymptomatic over
      the course of the pre-season. All four echo-types were significantly different at
      the end of the pre-season, with the overall echopattern suggesting an improvement
      in Achilles tendon structure. Three of the 18 participants developed Achilles
      tendon pain that coincided with a change in the UTC echopattern. This study
      demonstrates that the UTC echopattern of the Achilles tendon improves over a 5
      month pre-season training period, representing increased fibrillar alignment.
      However, further investigation is needed to elucidate with this alteration in the
      UTC echopattern results in improved tendon resilience and load capacity. 

PMID- 25943891
TI  - Sox2 function as a negative regulator to control HAMP expression.
AB  - BACKGROUND: Hepcidin, encoding by HAMP gene, is the pivotal regulator of iron
      metabolism, controlling the systemic absorption and transportation of irons from
      intracellular stores. Abnormal levels of HAMP expression alter plasma iron
      parameters and lead to iron metabolism disorders. Therefore, it is an important
      goal to understand the mechanisms controlling HAMP gene expression. RESULTS:
      Overexpression of Sox2 decrease basal expression of HAMP or induced by IL-6 or
      BMP-2, whereas, knockdown of Sox2 can increase HAMP expression, furthermore, two
      potential Sox2-binding sites were identified within the human HAMP promoter.
      Indeed, luciferase experiments demonstrated that deletion of any Sox2-binding
      site impaired the negative regulation of Sox2 on HAMP promoter transcriptional
      activity in basal conditions. ChIP experiments showed that Sox2 could directly
      bind to these sites. Finally, we verified the role of Sox2 to negatively regulate
      HAMP expression in human primary hepatocytes. CONCLUSION: We found that Sox2 as a
      novel factor to bind with HAMP promoter to negatively regulate HAMP expression,
      which may be further implicated as a therapeutic option for the amelioration of
      HAMP-overexpression-related diseases, including iron deficiency anemia.

PMID- 25943893
TI  - A novel red-emitting phosphor, KAl1-xPO4Cl:Eux(3+) (0.1 <= x <= 1.0).
AB  - A series of phosphors KAl1-xPO4Cl:Eux(3+) (0.1 <= x <= 1.0) was synthesized using
      a facile combustion method using urea as a fuel and their structural,
      morphological and photoluminescence properties were investigated. It was found
      that the particle size was in the range of 1-2 um with an irregular shape. The f
      f transitions of Eu(3+)  in the host lattice were assigned and discussed. The
      excitation and emission spectra indicated that this phosphor can be efficiently
      excited by ultraviolet (395 nm), and exhibit reddish orange emission
      corresponding to the (5)D0 ->(7)FJ (J = 0, 1, 2) transitions of Eu(3+). The
      impact of the Eu(3+) concentration on the relative emission intensity was
      investigated, and the best doping concentration is 0.5. The present study
      suggests that the KAl0.5PO4Cl:Eu0.5(3+) phosphor is a strong candidate as a red
      component for phosphor- converted white light-emitting diodes (LEDs).

PMID- 25943895
TI  - Measurement of amplitude of accommodation in young persons.
AB  - BACKGROUND: The aim was to evaluate the amplitude of accommodation using test
      objects designed with constant angular size corresponding to 6/6 visual acuity.
      METHODS: In total, 155 young volunteers with good ocular and systemic health aged
      between eight and 25 years were recruited for the study. A push-up method was
      conducted, with the near-vision target having a set of Landolt's broken circles.
      The angular size of the circles corresponded to a 6/6 visual acuity for various
      distances from 5.0 cm to 40 cm. To ensure precision of the object size, the
      electron beam lithographic technique was applied. RESULTS: A general trend in a
      reduction in amplitude with the progression of age is coincident with data from
      previous studies; however, the magnitudes of the volume of accommodation in our
      study are substantially lower. CONCLUSION: Test objects with constant angular
      size can increase the accuracy of 'push-up' accommodation measures.

PMID- 25943894
TI  - Differential immune mechanism to HIV-1 Tat variants and its regulation by AEA
      [corrected].
AB  - In the retina, Muller glia is a dominant player of immune response. The HIV-1
      transactivator viral protein (Tat) induces production of several neurotoxic
      cytokines in retinal cells. We show that HIV-1 clades Tat B and C act
      differentially on Muller glia, which is reflected in apoptosis, activation of
      cell death pathway components and pro-inflammatory cytokines. The harsher immune
      mediated pathology of Tat B, as opposed to milder effects of Tat C, manifests at
      several signal transduction pathways, notably, MAPK, STAT, SOCS, the NFkappaB
      signalosome, and TTP. In activated cells, anandamide (AEA), acting as an immune
      modulator, suppresses Tat B effect through MKP-1 but Tat C action via MEK-1. AEA
      lowers nuclear NF-kappaB and TAB2 for both variants while elevating IRAK1BP1 in
      activated Muller glia. Muller glia exposed to Tat shows enhanced PBMC attachment.
      Tat-induced increase in leukocyte adhesion to Muller cells can be mitigated by
      AEA, involving both CB receptors. This study identifies multiple signalling
      components that drive immune-mediated pathology and contribute to disease
      severity in HIV clades. We show that the protective effects of AEA occur at
      various stages in cytokine generation and are clade-dependant. 

PMID- 25943896
TI  - Method to Reduce Target Motion Through Needle-Tissue Interactions.
AB  - During minimally invasive surgical procedures, it is often important to deliver
      needles to particular tissue volumes. Needles, when interacting with a substrate,
      cause deformation and target motion. To reduce reliance on compensatory intra
      operative imaging, a needle design and novel delivery mechanism is proposed.
      Three-dimensional finite element simulations of a multi-segment needle inserted
      into a pre-existing crack are presented. The motion profiles of the needle
      segments are varied to identify methods that reduce target motion. Experiments
      are then performed by inserting a needle into a gelatine tissue phantom and
      measuring the internal target motion using digital image correlation. Simulations
      indicate that target motion is reduced when needle segments are stroked
      cyclically and utilise a small amount of retraction instead of being held
      stationary. Results are confirmed experimentally by statistically significant
      target motion reductions of more than 8% during cyclic strokes and 29% when also
      incorporating retraction, with the same net insertion speed. By using a multi
      segment needle and taking advantage of frictional interactions on the needle
      surface, it is demonstrated that target motion ahead of an advancing needle can
      be substantially reduced. 

PMID- 25943897
TI  - Expression of Smad7 and Smad ubiquitin regulatory factor 2 in a rat model of
      chronic pancreatitis.
AB  - OBJECTIVE: To quantify the expressions of Smad7 and Smad ubiquitin regulatory
      factor 2 (Smurf2) in the pancreas in rats with chronic pancreatitis (CP).
      METHODS: A total of 16 male Wistar rats were randomly divided into the control
      group and the CP group, with 8 rats in each group. CP was induced in vivo with
      dibutyltin dichloride (DBTC). Four weeks after DBTC administration, histological
      assessment and the measurement of hydroxyproline content in the pancreatic
      tissues were performed to assess the inflammation and fibrosis of the pancreas.
      Immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR)
      for transforming growth factor (TGF)-beta1 and alpha-smooth muscle actin (alpha
      SMA) were applied to assess activated pancreatic stellate cells (PSC) and TGF
      beta1 expression. Smad7 and Smurf2 expressions in the pancreas were measured
      using Western blot and RT-PCR. RESULTS: Typical histopathological characteristics
      of DBTC-induced CP in the rats with extensively activated PSC. Compared with the
      control group, the expressions of TGF-beta1, alpha-SMA and hydroxyproline content
      in the pancreatic tissues in the CP group were significantly increased.
      Meanwhile, the mRNA and protein expressions of Smad7 and Smurf2 were significant
      increased in the fibrotic pancreas, in which the expressions of Smad7 proteins
      showed an obvious reduction compared with controls. CONCLUSION: The dysregulation
      of Smad7 and Smurf2 may be associated with the pathogenesis of pancreatic
      fibrosis through the TGF-beta signaling pathway.

PMID- 25943899
TI  - Analysis of the shapes of hemocytes of Callista brevisiphonata in vitro
      (Bivalvia, Veneridae).
AB  - Fractal formalism in conjunction with linear methods of image analysis is
      suitable for the comparative analysis of such "irregular" shapes (from the point
      of view of classical Euclidean geometry) as flattened amoeboid cells of
      invertebrates in vitro. Cell morphology of in vitro spreading hemocytes from the
      bivalve mollusc Callista brevisiphonata was analyzed using correlation, factor
      and cluster analysis. Four significantly different cell types were identified on
      the basis of 36 linear and nonlinear parameters. The analysis confirmed the
      adequacy of the selected methodology for numerical description of the shape and
      the adequacy of classification of nonlinear shapes of spread hemocytes belonging
      to the same species. Investigation has practical significance for the description
      of the morphology of cultured cells, since cell shape is a result of summation of
      a number of extracellular and intracellular factors.

PMID- 25943898
TI  - Development and first validation of a simplified CT-based classification system
      of soft tissue changes in large-head metal-on-metal total hip replacement: intra-
      and interrater reliability and association with revision rates in a uniform
      cohort of 664 arthroplasties.
AB  - OBJECTIVE: After implantation of a metal-on-metal total hip arthroplasty (MoM
      THA), a large incidence of pseudotumor formation has been described recently.
      Several centers have invited patients for follow-up in order to screen for
      pseudotumor formation. The spectrum of abnormalities found by CT in MoM THA
      patients can be unfamiliar to radiologists and orthopedic surgeons. Previously, a
      CT five-point grading scale has been published. In this paper, a simplification
      into a three-point classification system gives insight in the morphological
      distinction of abnormalities of the postoperative hip capsule in MoM implants in
      relation to the decision for revision. The reliability of this simplified
      classification regarding intra- and interrater reliability and its association
      with revision rate is investigated and discussed. MATERIALS AND METHODS: All
      patients who underwent MoM THA in our hospital were invited for screening.
      Various clinical measures and CT scan were obtained in a cross-sectional fashion.
      A decision on revision surgery was made shortly after screening. CT scans were
      read in 582 patients, of which 82 patients were treated bilaterally. CT scans
      were independently single read by two board-certified radiologists and classified
      into categories I-V. In a second meeting, consensus was obtained. Categories were
      subsequently rubricated in class A (categories I and II), B (category III), and C
      (categories IV and V). Intra- and inter-radiologist agreement on MoM pathology
      was assessed by means of the weighted Cohen's kappa. Categorical data were
      presented as n (%), and tested by means of Fisher's exact test. Continuous data
      were presented as median (min-max) and tested by means of Mann-Whitney U test
      (two group comparison) or Kruskal-Wallis test (three group comparison). Logistic
      regression analysis was performed in order to study independence of CT class for
      association with revision surgery. Univariate statistically significant variables
      were entered in a multiple model. All statistical analysis was performed two
      tailed using alpha 5% as the significance level. RESULTS: In total, 664 scores
      from 664 MoM hips obtained by two observers were available for analyses.
      Interobserver reliability for the non-simplified version (I-V) was kappaw = 0.71
      (95% CI: 0.62-0.79), which indicates good agreement between the two
      musculoskeletal radiologists. Intra- and interobserver reliability for the
      simplified version (A-C) were respectively kappaw 0.78 (95% CI: 0.68-0.87), and
      kappaw = 0.71 (95% CI: 0.65-0.76). This indicates good agreement within and
      between the two observers. The simplified A-C version is significantly associated
      with revision exclusively due to MoM pathology, in both patients with unilateral
      MoM THA (p < 0.001) and patients with bilateral MoM THA (p < 0.044). The
      simplified A-C version is associated with several clinical measures. In patients
      with unilateral MoM THA, with or without contralateral THA, in situ time (p <
      0.008), cobalt and chromium (p < 0.001) were statistically significant. In
      patients with bilateral MoM, cobalt (p < 0.001) and chromium (p < 0.027) were
      statistically significant. Revision is significantly associated with cup size (p
      < 0.001), anteversion of the cup (p < 0.004), serum ion levels of cobalt and
      chromium (p < 0.001) and the adapted classification system (p < 0.001). In
      univariate logistic regression analysis on revision, cup, anteversion of the cup,
      cobalt-chromium ion serum levels, and the simplified (A-C) CT category system
      were statistically significant. The simplified (A-C) CT category system was an
      independent associate of revision, in several multiple logistic regression
      models. CONCLUSIONS: The presented simplified CT grading system (A-C) in its
      first clinical validation on 48- and 64-multislice systems is reliable, showing
      good intra- and interrater reliability and is independently associated with
      revision surgery.

PMID- 25943900
TI  - Resident Physicians and Cancer Health Disparities: a Survey of Attitudes,
      Knowledge, and Practice.
AB  - Workforce development initiatives designed to mitigate cancer health disparities
      focus primarily on oncologists rather than on primary care providers (PCPs) who
      could be better positioned to address the issue at the preventive and community
      levels. The purpose of this project was to assess primary care resident
      physicians' self-perceived attitudes and comfort level in addressing cancer
      health disparities. Resident physicians in their first- through third-year of
      training in family, internal, preventive/occupational medicine, and obstetrics
      and gynecology (OB/GYN) at three academic centers responded to a 13-question
      survey in the spring of 2013. Descriptive and chi-square statistics were
      performed to analyze responses to (1) attitudes about cross-cultural
      communication and understanding, (2) knowledge about sources of cancer health
      disparities, (3) self-reported preparedness to provide cross-cultural cancer care
      and skills to manage specific situations, and (4) relevance of cancer-disparity
      education to clinical practice. A total of 78 (70.9 %) residents responded to the
      survey. Twenty three (29.5 %) of the respondents felt they did not understand the
      socio-demographic characteristics of their patients' communities, and 20 (25.6 %)
      did not feel capable of discussing current cancer-related care guidelines when
      the patients' personal beliefs conflict with their own. Few of the relationships
      between residency program and location with outcome measures met the criteria for
      statistical significance. Family medicine residents were the most likely to
      report in that it was hard to interact with persons from other cultures. As PCPs
      will play a key role in addressing cancer health disparities, effective
      educational opportunities in cancer care by primary care residents are warranted.

PMID- 25943901
TI  - Providers' Perspectives of Survivorship Care for Young Adult Survivors of
      Childhood Cancer.
AB  - We examined healthcare providers' perceptions of the goals of survivorship care
      and survivor programs, systems-level barriers and individual patient-level
      barriers to engaging patients in survivorship care, and potential resources for
      increasing engagement. In 2012, we recruited 21 healthcare providers of young
      adult survivors of childhood cancers from a children's hospital and a cancer
      center in the Southeastern USA to complete telephone-based semi-structured
      interviews. The sample was 45.95 years old (SD = 7.57) on average, 52.4 % female,
      and 81.0 % MDs. The major goals of survivorship programs identified were medical
      care management (e.g., addressing late and long-term effects, providing
      survivorship care plans (SCPs), assisting in transition of care) and holistic
      care including addressing psychosocial issues and promoting healthy lifestyles.
      Systems-level barriers to engagement in survivorship care included limited
      resources (e.g., time), role confusion (e.g., within cancer centers, from
      treatment team to survivorship care, role of primary care providers),
      communication challenges within the medical system (e.g., limited tracking of
      patients, lack of understanding of the role of survivorship clinic),
      communication challenges with patients (e.g., setting expectations regarding
      transition to survivorship care), and lack of insurance coverage. Perceived
      patient-level factors included psychological barriers (e.g., fear, avoidance),
      resistance to survivorship care, and physical barriers (e.g., distance from
      survivorship clinics). Resources to address these barriers included increased
      access to information, technology-based resources, and ensuring valuable
      services. There are several systems-level and patient-level barriers to
      survivorship care, thus requiring multilevel interventions to promote engagement
      in care among young adult survivors of childhood cancer.

PMID- 25943902
TI  - Psychopathology in a Galaxy Far, Far Away: the Use of Star Wars' Dark Side in
      Teaching.
AB  - Star Wars is well known, timeless, universal, and incorporated into shared
      culture. Trainees have grown up with the movies, and based on their enduring
      popularity, attending psychiatrists are likely to have seen them too. This
      article highlights psychopathology from the Dark Side of Star Wars films which
      can be used in teaching. These include as follows: borderline and narcissistic
      personality traits, psychopathy, PTSD, partner violence risk, developmental
      stages, and of course Oedipal conflicts. 

PMID- 25943903
TI  - Future research and developments in hysteroscopy.
AB  - Hysteroscopy has become an important tool to evaluate intrauterine pathology. In
      most cases, the pathology can be diagnosed and treated in the office or
      outpatient setting. The ability to use normal saline as a distending medium
      allows the procedure to be performed using bipolar energy. During hysteroscopic
      myomectomy, visualization can remain unobstructed with the use of a hysteroscopic
      morcellator. Its use is also associated with decreased operating time. The use of
      Essure((r)) to block the proximal fallopian tube by a hysteroscopic approach is
      an approved procedure for tubal sterilization. However, it has been increasingly
      used to prevent hydrosalpinx fluid from entering the uterine cavity in women
      undergoing in vitro fertilization. The hysteroscopic approach has also been used
      to treat a variety of conditions such as treatment of interstitial pregnancy,
      caesarean scar pregnancy and retained placenta. However, the number of cases is
      still relatively small, and no randomized trial has ever been conducted. One of
      the potentially important developments is the use of falloposcopy to obtain
      distal tubal cytology as a screening for ovarian cancer. The technique remains to
      be refined. 

PMID- 25943905
TI  - Electrochemical polymerization of pyrene derivatives on functionalized carbon
      nanotubes for pseudocapacitive electrodes.
AB  - Electrochemical energy-storage devices have the potential to be clean and
      efficient, but their current cost and performance limit their use in numerous
      transportation and stationary applications. Many organic molecules are abundant,
      economical and electrochemically active; if selected correctly and rationally
      designed, these organic molecules offer a promising route to expand the
      applications of these energy-storage devices. In this study, polycyclic aromatic
      hydrocarbons are introduced within a functionalized few-walled carbon nanotube
      matrix to develop high-energy, high-power positive electrodes for pseudocapacitor
      applications. The reduction potential and capacity of various polycyclic aromatic
      hydrocarbons are correlated with their interaction with the functionalized few
      walled carbon nanotube matrix, chemical configuration and electronic structure.
      These findings provide rational design criteria for nanostructured organic
      electrodes. When combined with lithium negative electrodes, these nanostructured
      organic electrodes exhibit energy densities of ~350 Wh kg(-1)electrode at power
      densities of ~10 kW kg(-1)electrode for over 10,000 cycles. 

PMID- 25943904
TI  - XoxF encoding an alternative methanol dehydrogenase is widespread in coastal
      marine environments.
AB  - The xoxF gene, encoding a pyrroloquinoline quinone-dependent methanol
      dehydrogenase, is found in all known proteobacterial methylotrophs. In several
      newly discovered methylotrophs, XoxF is the active methanol dehydrogenase,
      catalysing the oxidation of methanol to formaldehyde. Apart from that, its
      potential role in methylotrophy and carbon cycling is unknown. So far, the
      diversity of xoxF in the environment has received little attention. We designed
      PCR primer sets targeting clades of the xoxF gene, and used 454 pyrosequencing of
      PCR amplicons obtained from the DNA of four coastal marine environments for a
      unique assessment of the diversity of xoxF in these habitats. Phylogenetic
      analysis of the data obtained revealed a high diversity of xoxF genes from two of
      the investigated clades, and substantial differences in sequence composition
      between environments. Sequences were classified as being related to a wide range
      of both methylotrophs and non-methylotrophs from Alphaproteobacteria,
      Betaproteobacteria and Gammaproteobacteria. The most prominent sequences detected
      were related to the family Rhodobacteraceae, the genus Methylotenera and the OM43
      clade of Methylophilales, and are thus related to organisms that employ XoxF for
      methanol oxidation. Furthermore, our analyses revealed a high degree of so far
      undescribed sequences, suggesting a high number of unknown bacterial species in
      these habitats. 

PMID- 25943906
TI  - Reintroduction of locally extinct vertebrates impacts arid soil fungal
      communities.
AB  - Introduced species have contributed to extinction of native vertebrates in many
      parts of the world. Changes to vertebrate assemblages are also likely to alter
      microbial communities through coextinction of some taxa and the introduction of
      others. Many attempts to restore degraded habitats involve removal of exotic
      vertebrates (livestock and feral animals) and reintroduction of locally extinct
      species, but the impact of such reintroductions on microbial communities is
      largely unknown. We used high-throughput DNA sequencing of the fungal internal
      transcribed spacer I (ITS1) region to examine whether replacing exotic
      vertebrates with reintroduced native vertebrates led to changes in soil fungal
      communities at a reserve in arid central Australia. Soil fungal diversity was
      significantly different between dune and swale (interdune) habitats. Fungal
      communities also differed significantly between sites with exotic or reintroduced
      native vertebrates after controlling for the effect of habitat. Several fungal
      operational taxonomic units (OTUs) found exclusively inside the reserve were
      present in scats from reintroduced native vertebrates, providing a direct link
      between the vertebrate assemblage and soil microbial communities. Our results
      show that changes to vertebrate assemblages through local extinctions and the
      invasion of exotic species can alter soil fungal communities. If local extinction
      of one or several species results in the coextinction of microbial taxa, the full
      complement of ecological interactions may never be restored. 

PMID- 25943907
TI  - Leg-length discrepancy is associated with low back pain among those who must
      stand while working.
AB  - BACKGROUND: Some studies suggest that leg length discrepancy (LLD) is associated
      with low back pain (LBP) but many have not found such an association leading to
      conflicting evidence on the role of LLD in LBP. METHODS: The study population
      consisted of meat cutters with a standing job and customer service workers with a
      sedentary job from Atria Suomi Ltd (Nurmo, Finland) who were at least 35 years
      old and had been working in their jobs for at least 10 years. Leg length of each
      participant was measured with a laser range meter fixed in a rod, which was
      holding the scanning head of the ultrasound apparatus. Association of the
      intensity of LBP (10-cm Visual Analog Scale) with LLD was analysed by linear
      regression model, while the hurdle model was used in analysing the association of
      number of days with LBP and days on sick leave during the past year. Associations
      were adjusted by gender, age, BMI, smoking, depressive feelings and type of work
      (standing or sedentary job). RESULTS: The final study population consisted of 114
      meat cutters (26 females and 88 males) and 34 customer service workers (30
      females and four males). Forty-nine percent of the meat cutters and 44% of the
      customer service workers had LLD of at least 6 mm, while 16% and 15%,
      respectively, had LLD of at least 11 mm. In the whole study population, LLD of 6
      mm or more was associated with higher intensity of LBP and number of days with
      LBP. In the stratified analysis, both intensity of LBP and number of days of LBP
      were associated with LLD among meat cutters but not among customer service
      workers. The sick leaves during past year were slightly longer among those with
      LLD 10 mm or more, but the differences were not statistically significant.
      CONCLUSIONS: LLD, measured with a laser range meter, was associated with
      intensity of LBP and self-reported days with LBP during the past year among meat
      cutters engaged in standing work. TRIAL REGISTRATION: ISRCTN11898558--The role of
      leg length discrepancy in low back pain.

PMID- 25943908
TI  - Risk of cancer among firefighters in California, 1988-2007.
AB  - BACKGROUND: Most studies of firefighter cancer risks were conducted prior to 1990
      and do not reflect risk from advances in building materials. METHODS: A case
      control study using California Cancer Registry data (1988-2007) was conducted to
      evaluate the risk of cancer among firefighters, stratified by race. RESULTS: This
      study identified 3,996 male firefighters with cancer. Firefighters were found to
      have a significantly elevated risk for melanoma (odds ratio [OR] = 1.8; 95%
      confidence interval [CI] 1.4-2.1), multiple myeloma (OR 1.4; 95%CI 1.0-1.8),
      acute myeloid leukemia (OR 1.4; 95%CI 1.0-2.0), and cancers of the esophagus (OR
      1.6; 95%CI 1.2-2.1), prostate (OR 1.5; 95%CI 1.3-1.7), brain (OR 1.5; 95%CI 1.2
      2.0), and kidney (OR 1.3; 95%CI 1.0-1.6). CONCLUSIONS: In addition to observing
      cancer findings consistent with previous research, this study generated novel
      findings for firefighters with race/ethnicity other than white. It provides
      additional evidence to support the association between firefighting and several
      specific cancers.

PMID- 25943909
TI  - Bioengineering strategies to generate artificial protein complexes.
AB  - For many applications, increasing synergy between distinct proteins through
      organization is important for the specificity, regulation, and overall reaction
      efficiency. Although there are many examples of protein complexes in nature, a
      generalized method to create these complexes remains elusive. Many conventional
      techniques such as random chemical conjugation, physical adsorption onto
      surfaces, and encapsulation within matrices are imprecise approaches and can lead
      to deactivation of protein native functionalities. More "bio-friendly" approaches
      such as genetically fused proteins and biological scaffolds often can result in
      low yields and low complex stability. Alternatively, site-specific protein
      conjugation or ligation can generate artificial protein complexes that preserve
      the native functionalities of protein domains and maintain stability through
      covalent bonds. In this review, we describe three distinct methods to synthesize
      artificial protein complexes (genetic incorPoration of unnatural amino acids to
      introduce bio-orthogonal azide and alkyne groups to proteins, split-intein based
      expressed protein ligation, and sortase mediated ligation) and highlight
      interesting applications for each technique.

PMID- 25943910
TI  - Hepatic Resection Improved the Long-Term Survival of Patients with BCLC Stage B
      Hepatocellular Carcinoma in Asia: a Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: Hepatic resection has been increasingly performed in patients with
      Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC), but
      the current evidence supporting its efficacy remains controversial. The aim of
      this systematic review was to investigate the long-term survival and safety of
      hepatic resection compared to transarterial chemoembolization (TACE) alone for
      BCLC stage B HCC. METHODS: Eligible trials that compared hepatic resection with
      TACE alone for intermediate HCC were identified from the Embase, PubMed, Web of
      Science, and Cochrane databases. The study outcomes included overall survival
      (OS) rate and treatment-related complication rate. Hazard ratios (HRs) with a 95%
      confidence interval were used to measure the pooled effect according to a random
      effects or fixed-effects model, depending on the heterogeneity among the included
      studies. The heterogeneity among these trials statistically was evaluated using
      the chi(2) and I (2) tests. Sensitivity analyses were also performed. RESULTS: A
      total of 9 studies containing 4958 patients were included. The comparison between
      hepatic resection and TACE revealed a pooled HR for 3-year OS of 0.403 (95% CI
      0.364-0.446, p = 0.000; I (2) = 0 %, p = 0.643) and a pooled HR for 5-year OS of
      0.433 (95% CI 0.394-0.475, p = 0.000; I (2) = 0%, p = 0.468). An AFP level >400
      ng/ml and being HBV-positive were factors significantly correlated with overall
      survival. For treatment-related complications, the overall odds ratio (OR) for
      hepatic resection versus TACE was 0.990 (95% CI 0.934-1.049; p = 0.728; I (2) =
      64.5%, p = 0.060). CONCLUSION: Hepatic resection likely improved overall survival
      compared with TACE alone in BCLC stage B HCC patients, but did not increase the
      incidence of treatment-related complications. An AFP level >400 ng/ml and HBV
      positivity were significantly correlated with poor OS.

PMID- 25943911
TI  - Circulating Serum Exosomal miRNAs As Potential Biomarkers for Esophageal
      Adenocarcinoma.
AB  - BACKGROUND: The poor prognosis and rising incidence of esophageal adenocarcinoma
      highlight the need for improved detection methods. The potential for circulating
      microRNAs (miRNAs) as biomarkers in other cancers has been shown, but circulating
      miRNAs have not been well characterized in esophageal adenocarcinoma. We
      investigated whether circulating exosomal miRNAs have potential to discriminate
      individuals with esophageal adenocarcinoma from healthy controls and non
      dysplastic Barrett's esophagus. METHODS: Seven hundred fifty-eight miRNAs were
      profiled in serum circulating exosomes from a cohort of 19 healthy controls, 10
      individuals with Barrett's esophagus, and 18 individuals with locally advanced
      esophageal adenocarcinoma. MiRNA expression was assessed using all possible
      permutations of miRNA ratios per individual. Four hundred eight miRNA ratios were
      differentially expressed in individuals with cancer compared to controls and
      Barrett's esophagus (Mann-Whitney U test, P < 0.05). The 179/408 ratios
      discriminated esophageal adenocarcinoma from healthy controls and Barrett's
      esophagus (linear regression, P < 0.05; area under receiver operating
      characteristic (ROC) > 0.7, P < 0.05). A multi-biomarker panel (RNU6-1/miR-16-5p,
      miR-25-3p/miR-320a, let-7e-5p/miR-15b-5p, miR-30a-5p/miR-324-5p, miR-17-5p/miR
      194-5p) demonstrated enhanced specificity and sensitivity (area under ROC = 0.99,
      95% CI 0.96-1.0) over single miRNA ratios to distinguish esophageal
      adenocarcinoma from controls and Barrett's esophagus. CONCLUSIONS: This study
      highlights the potential for serum exosomal miRNAs as biomarkers for the
      detection of esophageal adenocarcinoma.

PMID- 25943912
TI  - Feasibility of Fast-Track Surgery in Elderly Patients with Gastric Cancer.
AB  - BACKGROUND: The aim of this study was to investigate the role of the fast-track
      surgery (FTS) program in elderly patients (aged >=75 years) who underwent open
      surgery for gastric cancer (GC) in China. METHODS: A total of 256 patients with
      GC were randomly assigned to four groups, each of which consisted of 64 cases:
      the 45-74-year-old age group was subdivided into the FTS-1 group and the
      conventional care (CC)-1 group, and the 75-89-year-old age group was subdivided
      into the FTS-2 group and the CC-2 group. All patients underwent open gastrectomy
      by the same experienced surgical team. We compared the differences between the
      pairs of groups in different age ranges with respect to the postoperative
      recovery index, complications, and medical costs. RESULTS: Compared with the CC-1
      group, the FTS-1 group exhibited earlier postoperative flatus, a shorter
      postoperative hospital stay, lower medical costs, and a decreased incidence of
      sore throat (P = 0.010, P = 0.000, P = 0.000, and P = 0.019, respectively).
      Compared with the CC-2 group, the FTS-2 group had more nausea and vomiting,
      stomach retention, and intestinal obstruction, as well as a higher readmission
      rate (P = 0.015, P = 0.011, P = 0.041, and P = 0.013, respectively). CONCLUSION:
      The application of FTS can significantly speed up postoperative rehabilitation,
      shorten the hospitalization time, and lower the medical costs for 45-74-year-old
      GC patients, but this procedure does not show the same benefits for elderly
      patients. These findings suggest that we should carefully consider whether the
      FTS program should be applied to elderly patients with GC.

PMID- 25943913
TI  - GC-FID determination and pharmacokinetic studies of oleanolic acid in human
      serum.
AB  - Analytical interest of OA determination in human serum has increased owing to the
      increasing interest in pharmaceutical research by pharmaceutical properties. A
      simple, specific, precise and accurate GC method with flame ionization detector
      (FID) developed and validated for the determination of oleanolic acid (OA) in
      human serum (HS). To an aliquot of HS, internal standard was added and a
      combination of liquid-liquid extraction with a mixture of diethyl ether-isopropyl
      alcohol, filtration and consecutive GC resulted in separation and quantification
      of OA. The organic phase was analyzed using a GC system equipped with a 30 * 0.25
      mm i.d. Rtx-65TG capillary column and FID detection. Total chromatographic time
      was 10 min and no interfering peaks from endogenous components in blank serum
      were observed. The OA/internal standard peak area ratio was linearly fitted to
      the OA concentration (r = 0.992) over the range 10-1500 ng/mL. The mean serum
      extraction recovery of OA was 96.7 +/- 1.0% and the lower limit of quantification
      based on 5 mL of serum was 10.7 ng/mL. The intra-day coefficient of variation
      ranged from 1.3 to 3.6% and inter-day varied from 1.4 to 4.5%. The developed
      method was used to study the pharmacokinetics of OA after oral administration in
      humans. The assay was simple, sensitive, precise and accurate for the use in the
      study of the mechanisms of absorption and distribution of OA in humans.

PMID- 25943914
TI  - Chemically induced fluorescence switching of carbon-dots and its multiple logic
      gate implementation.
AB  - Investigations were carried out on the carbon-dots (C-dots) based fluorescent off
      - on (Fe(3 + )- S2O3(2-)) and on - off (Zn(2 + )- PO4(3-)) sensors for the
      detection of metal ions and anions. The sensor system exhibits excellent
      selectivity and sensitivity towards the detection of biologically important Fe(3
      + ), Zn(2 + ) metal ions and S2O3(2-), PO4(3-) anions. It was found that the
      functional group on the C-dots surface plays crucial role in metal ions and
      anions detection. Inspired by the sensing results, we demonstrate C-dots based
      molecular logic gates operation using metal ions and anions as the chemical
      input. Herein, YES, NOT, OR, XOR and IMPLICATION (IMP) logic gates were
      constructed based on the selection of metal ions and anions as inputs. This
      carbon-dots sensor can be utilized as various logic gates at the molecular level
      and it will show better applicability for the next generation of molecular logic
      gates. Their promising properties of C-dots may open up a new paradigm for
      establishing the chemical logic gates via fluorescent chemosensors.

PMID- 25943915
TI  - Continuous transfer of liquid metal droplets across a fluid-fluid interface
      within an integrated microfluidic chip.
AB  - Micro scale liquid metal droplets have been hailed as the potential key building
      blocks of future micro-electro-mechanical systems (MEMS). However, most of the
      current liquid metal enabled systems involve millimeter scale droplets, which are
      manually injected onto the desired locations of the microchip. Despite its
      simplicity, this method is impractical for patterning large arrays or complex
      systems based on micro scale droplets. Here, we present a microfluidic chip,
      which integrates continuous generation of micro scale galinstan droplets in
      glycerol, and the hydrodynamic transfer of these droplets into sodium hydroxide
      (NaOH) solution. Observation via high-speed imaging along with computational
      fluid dynamics (CFD) analysis are utilised to comprehend the lateral migration of
      droplets from the glycerol to NaOH fluid. This platform is simple, can be readily
      integrated into other microfluidic systems, and creates flexibility by separating
      the continuous phase for droplet generation from the eventual target carrier
      fluid within a monolithic chip. 

PMID- 25943917
TI  - Towards better management of COPD.

PMID- 25943916
TI  - Fluorescent Visualisation of Oxytocin in the Hypothalamo-neurohypophysial/-spinal
      Pathways After Chronic Inflammation in Oxytocin-Monomeric Red Fluorescent Protein
      1 Transgenic Rats.
AB  - Oxytocin (OXT) is a well-known neurohypophysial hormone that is synthesised in
      the paraventricular (PVN) and supraoptic nuclei (SON) of the hypothalamus. The
      projection of magnocellular neurosecretory cells, which synthesise OXT and
      arginine vasopressin in the PVN and SON, to the posterior pituitary plays an
      essential role in mammalian labour and lactation through its peripheral action.
      However, previous studies have shown that parvocellular OXTergic cells in the
      PVN, which project to the medulla and spinal cord, are involved in various
      physiological functions (e.g. sensory modulation and autonomic). In the present
      study, we examined OXT expression in the PVN, SON and spinal cord after chronic
      inflammation from adjuvant arthritis (AA). We used transgenic rats that express
      OXT and the monomeric red fluorescent protein 1 (mRFP1) fusion gene to visualise
      both the magnocellular and parvocellular OXTergic pathways. OXT-mRFP1
      fluorescence intensity was significantly increased in the PVN, SON, dorsal horn
      of the spinal cord and posterior pituitary in AA rats. The levels of OXT-mRFP1
      mRNA were significantly increased in the PVN and SON of AA rats. These results
      suggested that OXT was up-regulated in both hypothalamic magnocellular
      neurosecretory cells and parvocellular cells by chronic inflammation, and also
      that OXT in the PVN-spinal pathway may be involved in sensory modulation. OXT
      mRFP1 transgenic rats are a very useful model for visualising the OXTergic
      pathways from vesicles in a single cell to terminals in in vitro preparations. 

PMID- 25943918
TI  - Growing older with congenital heart disease.

PMID- 25943919
TI  - Migrant crisis in the Mediterranean.

PMID- 25943920
TI  - Ageing, health, and social care: reframing the discussion.

PMID- 25943924
TI  - UK political parties make pledges for the wider world.

PMID- 25943925
TI  - India makes good progress in combating kala-azar.

PMID- 25943927
TI  - Wayne Riley: energetic new president for century-old ACP.

PMID- 25943928
TI  - Osler redux: the American College of Physicians at 100.

PMID- 25943929
TI  - Sheila Kitzinger.

PMID- 25943930
TI  - Risk factors for and origins of COPD.

PMID- 25943931
TI  - Tobacco plain packaging: too hot for regulatory chill.

PMID- 25943932
TI  - Informed use of bedaquiline for tuberculosis.

PMID- 25943933
TI  - Informed use of bedaquiline for tuberculosis.

PMID- 25943934
TI  - Dengue vaccine--time to act now.

PMID- 25943935
TI  - Informed use of bedaquiline for tuberculosis--Authors' reply.

PMID- 25943936
TI  - Differential efficacy of dengue vaccine by immune status.

PMID- 25943937
TI  - Suicide rates in the aftermath of the 2011 earthquake in Japan.

PMID- 25943938
TI  - An active shooter in our hospital.

PMID- 25943939
TI  - Department of Error.

PMID- 25943940
TI  - Department of Error.

PMID- 25943941
TI  - Department of Error.

PMID- 25943944
TI  - An epigenetic cause of seizures and brain calcification:
      pseudohypoparathyroidism.

PMID- 25943942
TI  - Early chronic obstructive pulmonary disease: definition, assessment, and
      prevention.
AB  - Chronic obstructive pulmonary disease (COPD) is the third leading cause of death
      worldwide. COPD, however, is a heterogeneous collection of diseases with
      differing causes, pathogenic mechanisms, and physiological effects. Therefore a
      comprehensive approach to COPD prevention will need to address the complexity of
      COPD. Advances in the understanding of the natural history of COPD and the
      development of strategies to assess COPD in its early stages make prevention a
      reasonable, if ambitious, goal. 

PMID- 25943945
TI  - C12-15 alkyl benzoate: a new cosmetic allergen?

PMID- 25943943
TI  - Current concepts in targeting chronic obstructive pulmonary disease
      pharmacotherapy: making progress towards personalised management.
AB  - Chronic obstructive pulmonary disease (COPD) is a common, complex, and
      heterogeneous disorder that is responsible for substantial and growing morbidity,
      mortality, and health-care expense worldwide. Of imperative importance to
      decipher the complexity of COPD is to identify groups of patients with similar
      clinical characteristics, prognosis, or therapeutic needs, the so-called clinical
      phenotypes. This strategy is logical for research but might be of little clinical
      value because clinical phenotypes can overlap in the same patient and the same
      clinical phenotype could result from different biological mechanisms. With the
      goal to match assessment with treatment choices, the latest iteration of
      guidelines from the Global Initiative for Chronic Obstructive Lung Disease
      reorganised treatment objectives into two categories: to improve symptoms (ie,
      dyspnoea and health status) and to decrease future risk (as predicted by forced
      expiratory volume in 1 s level and exacerbations history). This change thus moves
      treatment closer to individualised medicine with available bronchodilators and
      anti-inflammatory drugs. Yet, future treatment options are likely to include
      targeting endotypes that represent subtypes of patients defined by a distinct
      pathophysiological mechanism. Specific biomarkers of these endotypes would be
      particularly useful in clinical practice, especially in patients in which
      clinical phenotype alone is insufficient to identify the underlying endotype. A
      few series of potential COPD endotypes and biomarkers have been suggested.
      Empirical knowledge will be gained from proof-of-concept trials in COPD with
      emerging drugs that target specific inflammatory pathways. In every instance,
      specific endotype and biomarker efforts will probably be needed for the success
      of these trials, because the pathways are likely to be operative in only a subset
      of patients. Network analysis of human diseases offers the possibility to improve
      understanding of disease pathobiological complexity and to help with the
      development of new treatment alternatives and, importantly, a reclassification of
      complex diseases. All these developments should pave the way towards personalised
      treatment of patients with COPD in the clinic. 

PMID- 25943946
TI  - Evaluation of chromatographic columns packed with semi- and fully porous
      particles for benzimidazoles separation.
AB  - The behavior of 15 benzimidazoles, including their main metabolites, using
      several C18 columns with standard or narrow-bore diameters and different particle
      size and type were evaluated. These commercial columns were selected because
      their differences could affect separation of benzimidazoles, and so they can be
      used as alternative columns. A simple screening method for the analysis of
      benzimidazole residues and their main metabolites was developed. First, the
      separation of benzimidazoles was optimized using a Kinetex C18 column; later,
      analytical performances of other columns using the above optimized conditions
      were compared and then individually re-optimized. Critical pairs resolution,
      analysis run time, column type and characteristics, and selectivity were
      considered for chromatographic columns comparison. Kinetex XB was selected
      because it provides the shortest analysis time and the best resolution of
      critical pairs. Using this column, the separation conditions were re-optimized
      using a factorial design. Separations obtained with the different columns tested
      can be applied to the analysis of specific benzimidazoles residues or other
      applications. 

PMID- 25943947
TI  - Change in blood protein detects more ovarian cancers than fixed threshold, study
      finds.

PMID- 25943948
TI  - Stability of postoperative delirium psychomotor subtypes in individuals with hip
      fracture.
AB  - OBJECTIVES: To determine the stability of psychomotor subtypes of delirium over
      time and identify characteristics associated with delirium psychomotor subtypes
      in individuals undergoing surgical repair of hip fracture. DESIGN: Prospective
      cohort study. SETTING: The Transfusion Trigger Trial for Functional Outcomes in
      Cardiovascular Patients Undergoing Surgical Hip Fracture Repair Cognitive
      Ancillary Study was conducted at 13 participating sites from 2008 to 2009.
      PARTICIPANTS: Individuals who had undergone surgical repair of hip fracture
      (N=139). MEASUREMENTS: Delirium was assessed up to four times postoperatively
      using the Confusion Assessment Method (CAM) and the Memorial Delirium Assessment
      Scale. Psychomotor subtypes of delirium were categorized as hypoactive,
      hyperactive, mixed, and normal psychomotor activity. RESULTS: Incidence of
      postoperative delirium was 41% (n=57). Of 90 CAM-positive (CAM+) observations,
      56% were hypoactive, 10% were hyperactive, 21% were mixed, and 14% had normal
      psychomotor symptoms. Of 26 participants with more than one CAM+ assessment, 50%
      maintained subtype stability over time. Participants with hypoactive or normal
      psychomotor symptoms (n=31) were less likely to have chart documentation of
      delirium than participants with any hyperactive symptoms (n=19) (22% vs 58%,
      P=.009). CONCLUSION: Psychomotor subtypes of delirium often fluctuate from
      assessment to assessment, rather than representing fixed categories of delirium.
      Hypoactive delirium is the most common presentation of delirium but is the least
      likely to be documented by healthcare providers.

PMID- 25943949
TI  - Biological tests for major depressive disorder that involve leukocyte gene
      expression assays.
AB  - BACKGROUND: Development of easy-to-use biological diagnostic tests for major
      depressive disorder (MDD) may facilitate MDD diagnosis and delivery of optimal
      treatment. Here, we examined leukocyte gene expression to develop a biological
      diagnostic test for MDD. METHODS: 25 drug-naive MDD patients (MDDs) and 25 age-
      and sex-matched healthy subjects (Controls) participated in a pilot study. A
      subsequent replication study involved 20 MDDs and 18 Controls. We used custom
      made PCR array plates to examine mRNA levels of 40 candidate genes in leukocyte
      samples to assess whether any combination of these genes could be used to
      differentiate MDDs from Controls based on expression profiles. RESULTS: Among 40
      candidate genes, we identified a set of seven genes (PDGFC, SLC6A4, PDLIM5,
      ARHGAP24, PRNP, HDAC5, and IL1R2), each of which had expression levels that
      differed significantly between MDD and Control samples in the pilot study. To
      identify genes whose expression best differentiated between MDDs and Controls, a
      linear discriminant function was developed to discriminate between MDDs and
      Controls based on the standardized values of gene expression after Z-score
      transformation. Ultimately, five genes (PDGFC, SLC6A4, ARHGAP24, PRNP, and HDAC5)
      were selected for a multi-assay diagnostic test. In the pilot study, this
      diagnostic test demonstrated sensitivity and specificity of 80% and 92%,
      respectively. The replication study yielded nearly identical results, sensitivity
      of 85% and specificity of 89%. CONCLUSIONS: Using leukocyte gene expression
      profiles, we could differentiate MDDs from Controls with adequate sensitivity and
      specificity. Additional markers not yet identified might further improve the
      performance of this test.

PMID- 25943951
TI  - Burnout as a risk factor for antidepressant treatment - a repeated measures time
      to-event analysis of 2936 Danish human service workers.
AB  - Burnout is a state of emotional exhaustion, feelings of reduced personal
      accomplishment, and withdrawal from work thought to occur as a consequence of
      prolonged occupational stress. The condition is not included in the diagnostic
      classifications, but is considered likely to develop into depressive disorder in
      some cases. We examined the prospective association between burnout and
      antidepressant treatment, as an indicator of clinically significant mental
      disorder. We further investigated potential effect-modifiers of the association,
      to identify factors that may prevent this progression of burnout. We used
      questionnaire data from a three-wave study of Danish human service workers
      conducted during 1999-2005, linked with national register data on purchases of
      antidepressants (ATC: N06A). We included 4788 observations from 2936 individuals
      (81% women) and analysed data by Aalens additive hazards modeling, examining the
      risk of entering antidepressant treatment in relation to the level of work
      related burnout measured by the Copenhagen Burnout inventory. As effect-modifiers
      we examined both sociodemographic factors and a range of psychosocial work
      environment factors. The level of burnout predicted antidepressant treatment.
      This association was modified by sex (p < 0.01). In men, high vs. intermediate
      burnout was associated with a 5% increased risk of antidepressant treatment per
      year of follow-up. This risk difference was 1% for women. Due to the sex specific
      patterns, we restricted effect modification analyses to women. We found no effect
      modification by the examined work environment factors, though a sensitivity
      analysis indicated a possible stronger association in women of lower occupational
      position. In conclusion, burnout predicted antidepressant treatment, with a
      stronger association in men than women. We found no evidence of effect
      modification by any of the examined psychosocial work environment factors. 

PMID- 25943950
TI  - Resequencing and association analysis of coding regions at twenty candidate genes
      suggest a role for rare risk variation at AKAP9 and protective variation at NRXN1
      in schizophrenia susceptibility.
AB  - A fraction of genetic risk to develop schizophrenia may be due to low-frequency
      variants. This multistep study attempted to find low-frequency variants of high
      effect at coding regions of eleven schizophrenia susceptibility genes supported
      by genome-wide association studies (GWAS) and nine genes for the DISC1
      interactome, a susceptibility gene-set. During the discovery step, a total of 125
      kb per sample were resequenced in 153 schizophrenia patients and 153 controls
      from Galicia (NW Spain), and the cumulative role of low-frequency variants at a
      gene or at the DISC1 gene-set were analyzed by burden and variance-based tests.
      Relevant results were meta-analyzed when appropriate data were available. In
      addition, case-only putative damaging variants were genotyped in a further 419
      cases and 398 controls. The discovery step revealed a protective effect of rare
      missense variants at NRXN1, a result supported by meta-analysis (OR = 0.67, 95%
      CI: 0.47-0.94, P = 0.021, based on 3848 patients and 3896 controls from six
      studies). The follow-up step based on case-only putative damaging variants
      revealed a promising risk variant at AKAP9. This variant, K873R, reached nominal
      significance after inclusion of 240 additional Spanish controls from databases.
      The variant, located in an ADCY2 binding region, is absent from large public
      databases. Interestingly, GWAS revealed an association between common ADCY2
      variants and bipolar disorder, a disorder with considerable genetic overlap with
      schizophrenia. These data suggest a role of rare missense variants at NRXN1 and
      AKAP9 in schizophrenia susceptibility, probably related to alteration of the
      excitatory/inhibitory synaptic balance, deserving further investigation.

PMID- 25943952
TI  - Age-dependent Muller glia neurogenic competence in the mouse retina.
AB  - The mechanisms limiting neuronal regeneration in mammals and their relationship
      with reactive gliosis are unknown. Muller glia (MG), common to all vertebrate
      retinas, readily regenerate neuron loss in some species, but normally not in
      mammals. However, experimental stimulation of limited mammalian retina
      regeneration has been reported. Here, we use a mouse retina organ culture
      approach to investigate the MG responses at different mouse ages. We found that
      MG undergo defined spatio-temporal changes upon stimulation. In EGF-stimulated
      juvenile postmitotic retinas, most MG upregulate cell-cycle regulators (Mcm6,
      Pcna, Ki67, Ccnd1) within 48 h ex vivo; some also express the neurogenic factors
      Ascl1, Pax6, and Vsx2; up to 60% re-enter the cell cycle, some of which
      delaminate to divide mostly apically; and the majority cease to proliferate after
      stimulation. A subpopulation of MG progeny starts to express transcription
      factors (Ptf1a, Nr4a2) and neuronal (Calb1, Calb2, Rbfox3), but not glial,
      markers, indicating neurogenesis. BrdU-tracking, genetic lineage-tracing, and
      transgenic-reporter experiments suggest that MG reprogram to a neurogenic stage
      and proliferate; and that some MG progeny differentiate into neuronal-like cells,
      most likely amacrines, no photoreceptors; most others remain in a de
      differentiated state. The mouse MG regeneration potential becomes restricted,
      dependent on the age of the animal, as observed by limited activation of the cell
      cycle and neurogenic factors. The stage-dependent analysis of mouse MG revealed
      similarities and differences when compared with MG-derived regeneration in fish
      and chicks. Therefore, the mouse retina ex vivo approach is a potential assay for
      understanding and overcoming the limitations of mammalian MG-derived neuronal
      regeneration. Postmitotic MG in mouse retina ex vivo can be stimulated to
      proliferate, express neurogenic factors, and generate progeny expressing neuronal
      or glial markers. This potential regenerative competence becomes limited with
      increasing mouse age.

PMID- 25943953
TI  - What is your diagnosis? Cytogram triple threat.

PMID- 25943954
TI  - Frequency and socio-psychological impact of taunting in school-age patients with
      cleft lip-palate surgical repair.
AB  - OBJECTIVES: Cleft lip-palate (CLP) is a "social" pathology because of its impact
      on the child's facial appearance and speech. School is the first place where
      children are confronted to others and when they start socializing. Taunting and
      bullying are common and their psychological impact remains hard to assess. The
      aim of this study was to evaluate the importance of taunting in school and its
      impact in CLP patients who had surgical repair. METHODS: We conducted a
      multicenter prospective study where we consecutively included patients >= 12
      years who had CLP repair. During a multidisciplinary consultation they were asked
      to complete a questionnaire (3 parts: surgical outcomes, taunting and its impact,
      socio-economic status) previously approved by our psychologists. RESULTS: 55
      patients were included (37 B, 18 G) (mean age 15.5 years): 11 CL, 13 CP and 31
      CLP. 69% of patients reported having suffered from taunting and peer
      victimization in school. In 84% of the cases, taunting was linked to the CLP
      defect itself. The teasing started in primary school to reach a peak of
      aggressiveness in middle school. 42% of patients reported that bullying occurred
      at least once a day (16/38). Regarding the psychological impact of taunting, 50%
      of patients reported sadness, 31% depression and 26.3% were marked for life. At
      one time or another 29% of patients did not want to attend school because of the
      teasing. The grade retention rate amounted to 37.7% (20/53), and 2 patients were
      in special education classes. As a matter of fact, 50% of these children repeated
      their 1st or 2nd year of primary school. Furthermore, 47% of patients wanted to
      change something to their face, but 63% of them never spoke to their surgeon
      about additional surgeries even though they were teased in school. CONCLUSIONS:
      Taunting is common in children with CLP. This study highlights the high frequency
      and impact of taunting on the daily lives and self-perception of patients with
      CLP or CLP repair. It is important for healthcare professionals to be aware of
      this issue in the context of a multidisciplinary approach.

PMID- 25943955
TI  - Nocardia asteroides sinusitis in a pediatric patient: Case report with 20 year
      follow-up and review of the literature.
AB  - Nocardia Asteroides infection in a non-immunocompromised pediatric patient is
      extremely rare. We present a case of ethmoid sinusitis and orbital subperiosteal
      abscess caused by N. asteroides with a 20 year follow up and a review of the
      literature. N. asteroides was grown from intraoperative cultures for mycobacteria
      following surgical incision and drainage of the abscess. Postoperatively, the
      patient received a seven month course of trimethoprim-sulfamethozaxole and had no
      subsequent sequelae. Nocardia infections are common in immunocompromised
      patients. We present what we believe to be the first case of pediatric Nocardia
      sinusitis with 20-year follow up. 

PMID- 25943956
TI  - Selective endocytic trafficking in live cells with fluorescent naphthoxazoles and
      their boron complexes.
AB  - Fluorescent naphthoxazoles and their boron derivatives have been synthesized and
      applied as superior and selective probes for endocytic pathway tracking in live
      cancer cells. The best fluorophores were compared with the commercially available
      acridine orange (co-staining experiments), showing far better selectivity. 

PMID- 25943957
TI  - Acupuncture and allergic rhinitis.
AB  - PURPOSE OF REVIEW: Allergic rhinitis has a high prevalence and negatively impacts
      quality of life. Patients commonly use complementary and integrative modalities
      to help alleviate their symptoms of allergic rhinitis, with approximately one in
      five receiving acupuncture. This article reviews the evidence base on the
      efficacy/effectiveness, safety and cost-effectiveness of acupuncture for allergic
      rhinitis. RECENT FINDINGS: Our review of the medical literature from January 2013
      through December 2014 revealed that there is research demonstrating efficacy and
      effectiveness for acupuncture in the treatment of allergic rhinitis, as well as
      improvement of quality of life and quality-adjusted life-years. SUMMARY: There
      are high-quality randomized controlled trials that demonstrate efficacy and
      effectiveness for acupuncture in the treatment of both seasonal and perennial
      allergic rhinitis. Smaller head-to-head studies also show some preliminary
      benefit of acupuncture when compared with antihistamines, but these had a variety
      of methodological limitations. Further studies of higher quality are needed,
      particularly with a focus on comparative effectiveness research.

PMID- 25943958
TI  - Integrative medical approaches to allergic rhinitis.
AB  - PURPOSE OF REVIEW: Complementary and integrative medicine (CIM), formerly known
      as alternative medicine, is now part of the mainstream management for patients
      with a host of medical issues. This current opinion focuses on the use of CIM,
      more specifically, the use of nutritional and herbal therapies and homeopathic
      medications for patients with allergic symptoms. RECENT FINDINGS: The literature
      review revealed that naturally occurring substances when compared with placebo
      more often than not resulted in significant improvement of the allergic rhinitis
      symptoms. SUMMARY: Despite encouraging results, additional studies with greater
      rigor are needed.

PMID- 25943959
TI  - Teaching laryngeal endoscopy skills to speech and language therapists: applying
      learning theory to optimize practical skills mastery.
AB  - PURPOSE OF REVIEW: This review was carried out to highlight relevant learning
      theory and its application to the teaching of endoscopic skills to speech and
      language therapists (SLTs). This article explains the most relevant models from
      Constructivist, Experiential and Humanistic Learning Theory, a combination that
      has been described as Constructive Experience, and describes the relevance and
      the benefits of applying educational frameworks in course design. This approach
      has been formally used to design and deliver practical skills teaching in
      medicine. RECENT FINDINGS: SLTs carry out endoscopic evaluation of the larynx
      (EEL) to provide information for evaluation and rehabilitation of voice and
      swallowing disorders. These are essential procedures in ear, nose and throat,
      voice and swallowing specialist centres. Training in endoscopy skills for SLTs
      working in the ear, nose and throat specialist centres in the United Kingdom has
      traditionally been provided external to the local clinic environment as 1 or 2
      day courses. In one survey in the United Kingdom, 79% of SLTs reported that they
      did not acquire the depth of skill required to carry out EEL autonomously after
      attending such courses. Course development to teach practical skills should be
      underpinned by educational theory. SUMMARY: One EEL course in the United Kingdom
      is described, wherein sessions are interactive and experiential, promoting deep
      learning, constructive feedback and reflection, enriched by the completion of
      logs and portfolios. From course evaluations, all the learners met the learning
      objectives, developing and applying skills to become confident endoscopists in
      autonomous clinical practice.

PMID- 25943960
TI  - Comparative costs of subcutaneous and sublingual immunotherapy.
AB  - PURPOSE OF REVIEW: This article describes the most recent comparative cost
      evaluations for subcutaneous (SCIT) and sublingual (SLIT) immunotherapy. RECENT
      FINDINGS: Only one recent article compares the costs of SCIT and SLIT in America.
      No American publications assess direct and indirect costs together. Few studies
      outside of America assess these costs in detail. SUMMARY: Limited data exist on
      the direct and indirect costs of SCIT and SLIT in the United States. Studies
      suggest that SLIT may be more affordable when taking indirect costs into account.
      Costs for SLIT may be more contained if physicians are more selective in the
      number and volume of antigens utilized per patient. Recent Food and Drug
      Administration approval of select sublingual tablets in America is changing the
      payment methodology for SLIT in America. Limited data on the cost in America call
      for further American studies on this topic.

PMID- 25943961
TI  - Allergy in the geriatric population.
AB  - PURPOSE OF REVIEW: Allergies and asthma have long been considered diseases of
      children and young adults. They are, however, prevalent among older patients
      also. This article summarizes findings on the diagnosis and treatment of
      allergies and asthma in the older population. RECENT FINDINGS: Allergies and
      asthma occur with fair frequency in older patients. Remembering to look and test
      for these problems enables better treatment and symptom control for these
      patients. Immunotherapy works well in this population. SUMMARY: Regardless of the
      patient's age, the differential diagnosis for sinonasal and dyspnea complaints
      should include allergies and asthma. Diagnosis is straightforward, and
      appropriate treatment improves quality of life.

PMID- 25943962
TI  - Update on eosinophilic esophagitis.
AB  - PURPOSE OF REVIEW: The prevalence of eosinophilic esophagitis (EoE) is
      increasing. It is important for practitioners to be aware of the disease and its
      presenting symptoms. RECENT FINDINGS: It is important to distinguish EoE from
      proton-pump inhibitor (PPI)-responsive esophageal eosinophilia. Patients with PPI
      responsive esophageal eosinophilia exhibit symptoms of esophageal dysfunction
      (often with endoscopic findings suggestive of EoE) with esophageal eosinophilia
      that responds to PPI treatment. SUMMARY: EoE was identified as a 'new disease'
      over 20 years ago. Two consensus articles have since been published (as well as
      an evidence-based approach to the diagnosis and management) highlighting
      diagnostic criteria, treatment options and potential complications of untreated
      disease. There is still much that needs to be learned and there are still many
      controversies left unanswered. No cure has been identified for EoE. Current
      therapy revolves around diet restriction and use of steroids to reduce the number
      of eosinophils in the esophagus and improve symptom control. Possibly future
      research will identify new targets for treatment that hopefully will lead to new
      treatment options for patients suffering with this disease as well as
      nonendoscopic methods to monitor treatment response.

PMID- 25943963
TI  - Change to earlier surgical interventions: contemporary management of unilateral
      vocal fold paralysis.
AB  - PURPOSE OF REVIEW: The management of unilateral vocal fold paralysis has
      undergone significant changes in the last 2 decades. This has largely been made
      possible by advances in endoscope technology and new injectable materials. RECENT
      FINDINGS: This article will cover the main changes in management of patients with
      unilateral vocal fold paralysis and summarize the recent literature in relation
      to early intervention in this group. Several recent studies have suggested that
      early vocal fold injection medialization reduces the likelihood of needing open
      laryngeal framework surgery in future. SUMMARY: Early injection medialization
      appears to give good long-term results with few complications and minimizes the
      need for future laryngeal framework surgery. It should be considered in centres
      wherein the equipment and trained staff are available.

PMID- 25943964
TI  - Swallowing after laryngectomy.
AB  - PURPOSE OF REVIEW: This article examines the emergence of dysphagia as an area
      for rehabilitation postlaryngectomy. The use of dysphagia evaluation tools
      postlaryngectomy is described and the causes of dysphagia discussed. RECENT
      FINDINGS: Although the risk of aspiration postlaryngectomy is low, significant
      symptoms of dysphagia can exist in this patient population. A comprehensive
      evaluation is the cornerstone for both the identification and management of
      postlaryngectomy dysphagia. The tool predominantly used to evaluate laryngectomy
      to date has been videofluoroscopy. The use of this tool in this patient
      population is described together with fibreoptic endoscopic evaluation of
      swallowing and manometry. Common causes for dysphagia postlaryngectomy are
      outlined. Some of the surgical and behavioural interventions used to manage
      postlaryngectomy dysphagia are discussed. SUMMARY: A significant proportion of
      postlaryngectomy patients can present with dysphagia. Comprehensive swallowing
      evaluation can illuminate the causes of dysphagia in this patient population and
      facilitate their management.

PMID- 25943965
TI  - Human papilloma virus-related oropharyngeal cancer: opportunities and challenges
      in dysphagia management.
AB  - PURPOSE OF REVIEW: Human papilloma virus (HPV) has emerged as the most common
      cause of oropharyngeal cancer (OPC) compared with traditional causes of excess
      alcohol and tobacco use. In this article, we will discuss HPV-related OPC and the
      challenges and opportunities presented in dysphagia management relative to
      efforts to de-escalate treatment and improve outcomes. RECENT FINDINGS: It is
      becoming increasingly apparent that patients with HPV-positive disease appear to
      respond favourably to chemoradiation. Targeted chemoradiation is associated with
      severe early and late toxicities related to swallow function. Research is in
      progress to ascertain the benefit of treatment de-escalation with a particular
      focus on swallowing outcomes. Patients are younger and, with the improved
      outcomes reported in the literature, surviving longer with the consequences of
      their treatment. Given the changing demographic of this patient group, there are
      a number of opportunities to optimize swallowing outcomes, and this should be
      underpinned by detailed swallowing evaluation and counselling prior to treatment.
      A number of strategies have been suggested to improve swallowing outcomes;
      however, persisting and late-onset swallowing effects continue to be a risk.
      Transoral surgery is evolving as an option for the treatment of HPV-positive
      disease; however, more studies are required to understand functional outcomes.
      SUMMARY: Clinical trials are now underway to ascertain the effectiveness of
      tailored treatments for HPV-positive OPC with a focus on swallowing outcomes. It
      is encouraging that studies are now including detailed, multidimensional
      swallowing evaluation. Until such time as longitudinal data are available,
      patients should be treated by speech-language pathologists based on existing
      radiation treatment protocols and in the knowledge that patients may experience
      significant late swallowing difficulties.

PMID- 25943966
TI  - Evidence-based treatment of voice and speech disorders in Parkinson disease.
AB  - PURPOSE OF REVIEW: Voice and speech impairments are present in nearly 90% of
      people with Parkinson disease and negatively impact communication and quality of
      life. This review addresses the efficacy of Lee Silverman Voice Treatment (LSVT)
      LOUD to improve vocal loudness (as measured by vocal sound pressure level vocSPL)
      and functional communication in people with Parkinson disease. The underlying
      physiologic mechanisms of Parkinson disease associated with voice and speech
      changes and the strength of the current treatment evidence are discussed with
      recommendations for best clinical practice. RECENT FINDINGS: Two randomized
      control trials demonstrated that participants who received LSVT LOUD were
      significantly better on the primary outcome variable of improved vocSPL
      posttreatment than alternative and no treatment groups. Treatment effects were
      maintained for up to 2 years. In addition, improvements have been demonstrated in
      associated outcome variables, including speech rate, monotone, voice quality,
      speech intelligibility, vocal fold adduction, swallowing, facial expression and
      neural activation. Advances in technology-supported treatment delivery are
      enhancing treatment accessibility. SUMMARY: Data support the efficacy of LSVT
      LOUD to increase vocal loudness and functional communication in people with
      Parkinson disease. Timely intervention is essential for maximizing quality of
      life for people with Parkinson disease.

PMID- 25943967
TI  - Variation in the use of surveillance endomyocardial biopsy among pediatric heart
      transplant centers over time.
AB  - EMB is widely utilized for graft surveillance after HTx; however, there is
      significant variation in the frequency of surveillance EMB use during the first
      year post-HTx. The aim of this study was to assess changes in the utilization of
      surveillance EMB over time among member institutions of PHTS. A survey of PHTS
      centers assessing the frequency of surveillance EMB use during the first year
      post-HTx was conducted in 2006. The same survey was repeated in 2014 to assess
      changes in practice over time. The number of EMB in infants ranged from 0 to 9
      and in adolescents 0 to 16. The number of EMB decreased or remained unchanged in
      the majority of centers. Fewer EMB are performed in infants compared to
      adolescents and this practice did not change over time. There was a significant
      decrease in surveillance EMB use in adolescents (p = 0.012). International
      centers perform significantly fewer EMB in adolescents when compared to centers
      within the United States (p = 0.006). There continues to be significant variation
      in the utilization of surveillance EMB, with a shift toward less reliance on EMB
      for adolescents in the current era. Further research is necessary to determine
      the optimal frequency of invasive monitoring that reduces costs without
      compromising outcomes.

PMID- 25943968
TI  - The accordion suture technique: A modified rhinoplasty spreader flap.
AB  - In rhinoplasties, a spreader flap is a widely used alternative to dorsal
      reconstruction with spreader grafts; however, it has a limited ability to provide
      sufficient nasal dorsal width. The upper lateral cartilage (ULC) thickness is
      four times thinner than a spreader graft. This report presents an accordion
      suture technique for the ULC that involves simple sutures which fix each ULC (3
      times folded) to the septum. We performed this technique in 64 primary
      rhinoplasties, and the patients were followed up for approximately 18 months. The
      patients completed a questionnaire 12 months postoperatively, and reported marked
      satisfaction with the aesthetics and function. Furthermore, rhinomanometric
      analysis showed that nasal airway resistance (NAR) decreased significantly in the
      postoperative period. 

PMID- 25943969
TI  - Reporting statistical analyses in peer review journal articles.
AB  - As a regular referee for the Health Information and Libraries Journal, Richard
      Stephens--Winner of the 2014 Wellcome Trust Science Writing Prize--has been
      impressed by the science on offer in the Health Information and Libraries
      Journal. But he has also been struck by how often similar problems with
      statistical analysis reporting come up during the review process. Acknowledging
      that statistics can be scary, he advocates that they should be simply viewed as a
      means of communicating ideas. In this editorial, he provides some straightforward
      guidelines on reporting statistical analyses in peer review journal articles,
      highlights pitfalls to avoid and illustrates best practice to aim for.

PMID- 25943970
TI  - The health information seeking behaviour and needs of community health workers in
      Chandigarh in Northern India.
AB  - This article represents two-firsts for the feature--it is the first to report on
      a study outside the UK and the first to examine the health information needs of
      community health workers. Sonika Raj is pursuing PhD at the Centre for Public
      Health, Panjab University, Chandigarh, in India and she conducted her research in
      Chandigarh. The article outlines the important role that health workers at
      community level play in determining health outcomes in the developing world,
      including Chandigarh. It demonstrates that while those workers recognise their
      information needs, there are many issues affecting their ability to access health
      information effectively, not least their limited access to appropriate technology
      and training. AM.

PMID- 25943971
TI  - International trends in health science librarianship part 14: East Africa (Kenya,
      Uganda, Rwanda).
AB  - This is the 14th in a series of articles exploring international trends in health
      science librarianship in the 21st century. This is the second of four articles
      pertaining to different regions in the African continent. The present issue
      focuses on countries in East Africa (Kenya, Uganda and Rwanda). The next feature
      column will investigate trends in West Africa. JM. 

PMID- 25943972
TI  - Professional development through attending conferences: reflections of a health
      librarian.
AB  - In this article, guest writer Ruth Jenkins from Berkshire Heathcare Foundation
      Trust reflects on two conferences she attended in 2014, LILAC and SLA. Through
      the process of reflection, she considers the benefits that attending conferences
      can have to library and information professionals in the health sector. In
      particular, she discusses the opportunities and areas for learning and
      professional development that conferences can offer including evidence-based
      practice and current awareness, gaining new knowledge and objectivity, and
      networking and the unexpected benefits of conferences. Ruth also offers some
      practical hints and tips on ways to facilitate your attendance at conferences,
      including through awards and funding. H.S. 

PMID- 25943973
TI  - Peter Craddock.

PMID- 25943974
TI  - Intracranial pancreatic islet transplantation increases islet hormone expression
      in the rat brain and attenuates behavioral dysfunctions induced by MK-801
      (dizocilpine).
AB  - The treatment of rodents with non-competitive antagonist of the N-Methyl-D
      aspartate (NMDA) receptor, MK-801 (dizocilpine), induces symptoms of psychosis,
      deficits in spatial memory and impairment of synaptic plasticity. Recent studies
      have suggested that insulin administration might attenuate the cognitive
      dysfunctions through the modulatory effect on the expression of NMDA receptors
      and on the brain insulin signaling. Intrahepatic pancreatic islet transplantation
      is known as an efficient tool for correcting impaired insulin signaling. We
      examined the capacity of syngeneic islets grafted into the cranial subarachnoid
      cavity to attenuate behavioral dysfunctions in rats exposed to MK-801. Animals
      were examined in the open field (OF) and the Morris Water Maze (MWM) tests
      following acute or subchronic administration of MK-801. We found well
      vascularized grafted islets expressing insulin, glucagon and somatostatin onto
      the olfactory bulb and prefrontal cortex. Significantly higher levels of insulin
      were detected in the hippocampus and prefrontal cortex of transplanted animals
      compared to the non-transplanted rats. All animals expressed normal peripheral
      glucose homeostasis for two months after transplantation. OF tests revealed that
      rats exposed to MK-801 treatment, showed hyper-responsiveness in motility
      parameters and augmented center field exploration compared to intact controls and
      these effects were attenuated by the grafted islets. Moreover, in the MWM, the
      rats treated with MK-801 showed impairment of spatial memory that were partially
      corrected by the grafted islets. In conclusion, intracranial islet
      transplantation leads to the expression of islet hormones in the brain and
      attenuates behavioral and cognitive dysfunctions in rats exposed to MK-801
      administration without altering the peripheral glucose homeostasis.

PMID- 25943975
TI  - Nucleic Acid Testing of Organ Donors: Is the Glass Half Empty or Half Full?

PMID- 25943976
TI  - Advances in pharmacotherapy for allergic conjunctivitis.
AB  - INTRODUCTION: Allergy is the fifth leading group of chronic diseases, affecting
      as much as 40% of the first-world population. Its pathophysiology has a genetic
      component, and is driven by the immune system's sensitized response to antigens
      and environmental factors. As research continues to uncover the mediators
      responsible for ocular allergy, the development of novel drugs should progress.
      AREAS COVERED: A literature review of allergic conjunctivitis, ocular allergy and
      their treatment was performed using PubMed and Medline. Additional information is
      also included from clinicaltrials.gov and associated web sites for drugs
      currently in clinical trials. EXPERT OPINION: The initial step of therapy remains
      identification and avoidance of allergic triggers. The mainstay of treatment is
      the new generation of dual-acting antihistamines. Drugs that improve the
      magnitude and duration of relief, with greater subject responder rates, are
      gradually making their way into the clinic. Allergic conjunctivitis is a
      relatively easy disease to study because of the availability of models such as
      the conjunctival allergen challenge. New classes of drugs that target
      inflammatory pathways or mediators involved in the early and late-phase allergic
      response are being screened in these models and we are making progress in
      identifying the next generation of anti-allergic therapy.

PMID- 25943977
TI  - The 2014 governors' races and health care: a campaign web site analysis.
AB  - The November 2014 midterm election was the first election since key coverage
      provisions of the Affordable Care Act (ACA) were implemented, including the
      Medicaid expansion and creation of the health insurance exchanges. The pre
      election variability in the states' implementation of these provisions coupled
      with the large number of states selecting their next governor made the election
      important at the state level. To better understand the role of health care in the
      recent gubernatorial elections, we analyzed health policy content presented by 71
      candidates for governor on their campaign Web sites. Nearly 80% of all candidates
      discussed health policy on their Web site, including the subset of the 36 winning
      governors. The predominant focus of health policy content was on the ACA as a
      whole or its provisions. Medicaid was discussed more often by candidates in non
      expansion states than those from expansion states. Based on the statements of
      winning governors, we expect serious consideration of the Medicaid expansion to
      occur in at least 4 states, whereas 2 states may make efforts to reverse course.
      Relatively few winning governors (33%) mentioned the exchanges. Only 1 expressed
      interest in switching from the federal exchange to a state exchange, which has
      particular relevance given the Supreme Court's pending decision on King v.
      Burwell that could invalidate tax credits on the federal exchange. The prominence
      of health care in the gubernatorial campaigns strengthens the likelihood that
      governors will play an influential role in the health system's future, especially
      as the ACA undergoes further federal debate. 

PMID- 25943978
TI  - Development of a Time-Intensity Evaluation System for Consumers: Measuring
      Bitterness and Retronasal Aroma of Coffee Beverages in 106 Untrained Panelists.
AB  - In order to develop products that are acceptable to consumers, it is necessary to
      incorporate consumers' intentions into products' characteristics. Therefore,
      investigation of consumers' perceptions of the taste or smell of common beverages
      provides information that should be useful in predicting market responses. In
      this study, we sought to develop a time-intensity evaluation system for consumer
      panels. Using our system, we performed time-intensity evaluation of flavor
      attributes (bitterness and retronasal aroma) that consumers perceived after
      swallowing a coffee beverage. Additionally, we developed quantitative evaluation
      methods for determining whether consumer panelists can properly perform time
      intensity evaluation. In every trial, we fitted an exponential function to
      measured intensity data for bitterness and retronasal aroma. The correlation
      coefficients between measured time-intensity data and the fitted exponential
      curves were greater than 0.8 in about 90% of trials, indicating that we had
      successfully developed a time-intensity system for use with consumer panelists,
      even after just a single training trial using a nontrained consumer. We
      classified participants into two groups based on their consumption of canned
      coffee beverages. Significant difference was observed in only AUC of sensory
      modality (bitterness compared with retronasal aroma) among conventional TI
      parameters using two-way ANOVA. However, three-way ANOVA including a time course
      revealed significant difference between bitterness and retronasal aroma in the
      high-consumption group. Moreover, the high-consumption group more easily
      discriminated between bitterness and retronasal aroma than the low-consumption
      group. This finding implied that manufacturers should select consumer panelists
      who are suitable for their concepts of new products. 

PMID- 25943979
TI  - Making sense of DSM-5 mania with depressive features.
AB  - OBJECTIVE: The assessment of the depressive component during mania has become
      critical for the accurate diagnosis of mixed states, which were defined very
      narrowly in the past classification systems before Diagnostic and Statistical
      Manual of Mental Disorders (5th ed.). The aim of this study was to compare socio
      demographic, clinical and therapeutic characteristics, as well as clinical and
      functional outcomes, between manic patients with and without mixed features to
      validate the relevance of the Diagnostic and Statistical Manual of Mental
      Disorders (5th ed.) mixed specifier. METHODS: This is a subanalysis of a
      multicentre naturalistic study MANia Aguda y COnsumo de Recursos (acute mania and
      health resource consumption [MANACOR]) on the burden of mania in bipolar patients
      from four hospitals in Catalonia (Spain). The sample consisted of 169 adult
      patients presenting a manic episode and systematically assessed during a 6-month
      period. RESULTS: A total of 27% (n = 46/169) of manic patients showed mixed
      features. Total number of episodes (p = 0.027), particularly depressive and
      mixed, was greater in manic patients with mixed features, as well as depressive
      onset (p = 0.018), suicide ideation (p = 0.036), rapid cycling (p = 0.035) and
      personality disorders (p = 0.071). In contrast, a higher percentage of pure manic
      subjects were inpatients (p = 0.035), started the illness with mania (p = 0.018)
      and showed family history of bipolar disorder (p = 0.037), congruent psychotic
      symptoms (p = 0.001) and cannabis use (p = 0.006). At baseline, pure manic
      patients received more risperidone (p = 0.028), while mixed patients received
      more valproate (p = 0.049) and antidepressants (p = 0.005). No differences were
      found in syndromic recovery at the end of the study. However, depressive change
      was higher in the mixed group (p = 0.010), while manic change was higher in the
      pure manic group (p = 0.029). At the end of follow-up, the group with mixed
      features showed a significant trend towards higher psychosocial dysfunction.
      CONCLUSION: A total of 27% of manic patients showed mixed features. Groups
      differed regarding clinical characteristics, course of illness, psychosocial
      functioning, prescribed treatment and symptom progress. Depressive symptoms in
      mania should be routinely assessed and considered to guide treatment.

PMID- 25943980
TI  - The National Perinatal Depression Initiative: An evaluation of access to general
      practitioners, psychologists and psychiatrists through the Medicare Benefits
      Schedule.
AB  - OBJECTIVE: To evaluate the impact of the National Perinatal Depression Initiative
      on access to Medicare services for women at risk of perinatal mental illness.
      METHOD: Retrospective cohort study using difference-in-difference analytical
      methods to quantify the impact of the National Perinatal Depression Initiative
      policies on Medicare Benefits Schedule mental health usage by Australian women
      giving birth between 2006 and 2010. A random sample of women of reproductive age
      enrolled in Medicare who had not given birth where used as controls. The main
      outcome measures were the proportions of women giving birth each month who
      accessed a Medicare Benefits Schedule mental health items during the perinatal
      period (pregnancy through to the end of the first postnatal year) before and
      after the introduction of the National Perinatal Depression Initiative. RESULTS:
      The proportion of women giving birth who accessed at least one mental health item
      during the perinatal period increased from 88 to 141 per 1000 between 2007 and
      2010. The difference-in-difference analysis showed that while there was an
      overall increase in Medicare Benefits Schedule mental health item access as a
      result of the National Perinatal Depression Initiative, this did not reach
      statistical significance. However, the National Perinatal Depression Initiative
      was found to significantly increase access in subpopulations of women,
      particularly those aged under 25 and over 34 years living in major cities.
      CONCLUSION: In the 2 years following its introduction, the National Perinatal
      Depression Initiative was found to have increased access to Medicare funded
      mental health services in particular groups of women. However, an overall
      increase across all groups did not reach statistical significance. Further
      studies are needed to assess the impact of the National Perinatal Depression
      Initiative on women during childbearing years, including access to tertiary care,
      the cost-effectiveness of the initiative, and mental health outcomes. It is
      recommended that new mental health policy initiatives incorporate a planned
      strategic approach to evaluation, which includes sufficient follow-up to assess
      the impact of public health strategies.

PMID- 25943981
TI  - The thalamus as a putative biomarker in neurodegenerative disorders.
AB  - OBJECTIVE: This review provides a brief account of the clinically relevant
      functional neuroanatomy of the thalamus, before considering the utility of
      various modalities utilized to image the thalamus and technical challenges
      therein, and going on to provide an overview of studies utilizing structural
      imaging techniques to map thalamic morphology in the spectrum of
      neurodegenerative disorders. METHODS: A systematic search was conducted for peer
      reviewed studies involving structural neuroimaging modalities investigating the
      morphology (shape and/or size) of the thalamus in the spectrum of
      neurodegenerative disorders. RESULTS: While the precise role of the thalamus in
      the healthy brain remains unclear, there is a large body of knowledge
      accumulating which defines more precisely its functional connectivity within the
      connectome, and a burgeoning literature implicating its involvement in
      neurodegenerative disorders. It is proposed that correlation of clinical features
      with thalamic morphology (as a component of a quantifiable subcortical
      connectome) will provide a better understanding of neuropsychiatric dysfunction
      in various neurodegenerative disorders, potentially yielding clinically useful
      endophenotypes and disease biomarkers. CONCLUSION: Thalamic biomarkers in the
      neurodegenerative disorders have great potential to provide clinically meaningful
      knowledge regarding not only disease onset and progression but may yield targets
      of and perhaps a way of gauging response to future disease-modifying modalities.

PMID- 25943982
TI  - Does daily tobacco smoking affect outcomes after microdecompression for
      degenerative central lumbar spinal stenosis? - A multicenter observational
      registry-based study.
AB  - BACKGROUND: There are limited scientific data on the impact of smoking on patient
      reported outcomes following minimally invasive spine surgery. The aim of this
      multicenter observational study was to examine the relationship between daily
      smoking and patient-reported outcome at 1 year using the Oswestry Disability
      Index (ODI) after microdecompression for single- and two-level central lumbar
      spinal stenosis (LSS). Secondary outcomes were the length of hospital stays,
      perioperative and postoperative complications. METHOD: Data were collected
      through the Norwegian Registry for Spine Surgery (NORspine). RESULTS: A total of
      825 patients were included (619 nonsmokers and 206 smokers). For the whole
      patient population there was a significant difference between preoperative ODI
      and ODI at 1 year (17.3 points, 95% CI 15.93-18.67, p < 0.001). There was a
      significant difference in ODI change at 1 year between nonsmokers and smokers
      (4.2 points, 95% CI 0.98-7.34, p = 0.010). At 1 year 69.6% of nonsmokers had
      achieved a minimal clinically important difference (>=10 points ODI improvement)
      compared to 60.8% of smokers (p = 0.008). There was no difference between
      nonsmokers and smokers in the overall complication rate (11.6% vs. 9.2%, p =
      0.34). There was no difference between nonsmokers and smokers in length of
      hospital stays for either single-level (2.3 vs. 2.2 days, p = 0.99) or two-level
      (3.1 vs. 2.3 days, p = 0.175) microdecompression. Smoking was identified as a
      negative predictor for ODI change in a multiple regression analysis (p = 0.001)
      CONCLUSIONS: Nonsmokers experienced a significantly larger improvement at 1 year
      following microdecompression for LSS compared to smokers. Smokers were less
      likely to achieve a minimal clinically important difference. However, it should
      be emphasized that considerable improvement also was found among smokers.

PMID- 25943983
TI  - Is there a role for monocyte chemoattractant protein-1 in delirium? Novel
      observations in elderly hip fracture patients.
AB  - BACKGROUND: Delirium is common, associated with poor outcome, but its
      pathophysiology remains obscure. The aim of the present study was to study a
      possible role of monocyte chemoattractant protein-1 (MCP-1) in the development of
      delirium. FINDINGS: A prospective cohort of 19 hip fracture patients (median age
      83 years) were screened for delirium daily by validated methods. MCP-1 was
      measured on arrival and postoperatively. The number of patients with a raise in
      MCP-1 was statistically significantly higher in the group with delirium in the
      postoperative phase compared to the no-delirium group (5/6 vs. 1/7, p = .03).
      CONCLUSIONS: MCP-1 might play a role in the development of delirium.

PMID- 25943984
TI  - Enhancement of Curcumin Fluorescence by Ascorbic Acid in Bicontinuous
      Microemulsion.
AB  - Steady-state fluorescence spectro-photometric technique is used in this work to
      determine the chemical parameters of the complex formed between curcumin and
      ascorbic acid in bicontinuous microemuslion (BMUen). The BMUen liquid used is
      made up of a four-components system (water-oil-surfactant and co-surfactant (1
      pentanol)) in the ratio of 42.11:13.7:21.34:22.85 % w/w. The oil and surfactant
      used are tetradecane and cetyltrimethylammonium bromide. Curcumin is known to
      have low solubility in water, but liberally soluble in BMUen, hence the use of
      BMUen in this study. The observed fluorescence intensity of curcumin was enhanced
      by introduction of ascorbic acid to the curcumin solution. The increase in the
      fluorescence intensity showed a very good linearity with a regression coefficient
      of 0.9974. The association constant, Ka, that resulted between curcumin and
      ascorbic acid was calculated as 2.15 * 10(4) with the free energy of association,
      ?Ga, of -24.71 kJ/mol. The ratio of the complex that was formed by these two
      molecules was determined as 1:1.

PMID- 25943985
TI  - Erythrocyte Protoporphyrin Fluorescence as a Biomarker to Monitor the Anticancer
      Effect of Semecarpus Anacardium in DMBA Induced Mammary Carcinoma Rat Model.
AB  - Endogenous fluorescence has been proposed as a means of aiding the diagnosis of
      various malignancies. It has been suggested that erythrocytes may be the carriers
      of fluorophors that accumulate in cancer tissue and may be useful in the
      diagnosis and treatment of malignancies. Hence, the present study was designed to
      explore the spectrofluorimetric analysis of blood components as a marker for the
      analysis of mammary carcinoma treatment and also to bring about the protective
      effect of the drug Semecarpus anacardium on oxidative stress mediated damage of
      erythrocytes. Fluorescence spectra of the blood components were studied and also
      the level of lipid per oxides and antioxidant enzymes status in erythrocytes were
      determined in DMBA induced mammary carcinoma rats treated with Semecarpus
      anacardium Linn nut milk extract. Fluorescence emission spectroscopy of blood
      components are altered under cancer conditions and the drug effectively
      ameliorated these alterations in mammary carcinoma induced rats. The drug also
      effectively reduced the oxidative stress induced erythrocyte damage thereby
      restoring the erythrocytes antioxidant status. These results suggest that
      erythrocytes may be the carriers of fluorophors that accumulate in cancer tissue
      and hence acts as new biomarkers for the diagnosis and treatment. 

PMID- 25943986
TI  - Craniotomy for Glioma Resection: A Predictive Model.
AB  - BACKGROUND: Regulatory agencies are standardizing quality metrics on the basis of
      which surgical procedures will be evaluated. We attempted to create a predictive
      model of perioperative complications in patients undergoing craniotomies for
      glioma resection. METHODS: We performed a retrospective cohort study involving
      patients who underwent craniotomies for glioma resection from 2005-2011 and were
      registered in the National Inpatient Sample (NIS) database. A predictive model
      for complications was developed and validated. RESULTS: Overall, 21,384 patients
      underwent glioma resection. The respective inpatient postoperative risks were
      1.6% for death, 25.8% for discharge to rehabilitation, 4.0% for treated
      hydrocephalus, 0.7% for cardiac complications, 0.5% for respiratory
      complications, 0.8% for deep wound infection, 0.6% for deep venous thrombosis
      (DVT), 3.1% for pulmonary embolus (PE), and 1.3% for acute renal failure (ARF).
      Predictive models for individual complications were developed on the basis of a
      logistic regression analysis and subsequently validated in a bootstrapped sample.
      The models demonstrated good discrimination with areas under the curve (AUC) of
      0.71, 0.71, 0.69, 0.71, 0.74, 0.70, 0.73, 0.64, and 0.81 for postoperative risk
      of death, discharge to rehabilitation, hydrocephalus, cardiac complications,
      respiratory complications, deep wound infection, DVT, PE, and ARF, respectively.
      Additionally, the Hosmer-Lemeshow test was used to assess the calibration of all
      models. CONCLUSIONS: The presented models can assist in the preoperative
      estimation of the complication risk for glioma patients and be used as an adjunct
      for outcome benchmarking in this population.

PMID- 25943987
TI  - The IARC monographs: critics and controversy.
AB  - The monograph program of the International Agency for Research on Cancer (IARC),
      which relies on the efforts of volunteer Working Groups, uses a transparent
      approach to evaluate the carcinogenicity of agents for which scoping has
      determined that there is sufficient evidence to warrant a review. Because of the
      potentially powerful implications of the conclusions of the monographs and the
      sometimes challenging nature of the evidence reviewed, the monographs and the
      IARC process have been criticized from time to time. This commentary describes
      the IARC monograph process and addresses recent criticisms of the program,
      drawing on a recent defense of the program authored by 124 researchers. These
      authors concluded that the IARC processes are robust and transparent and not
      flawed and biased as suggested by some critics.

PMID- 25943988
TI  - Healthy or Unhealthy on Sale? A cross-sectional study on the proportion of
      healthy and unhealthy foods promoted through flyer advertising by supermarkets in
      the Netherlands.
AB  - BACKGROUND: It is generally assumed that supermarkets promote unhealthy foods
      more heavily than healthy foods. Promotional flyers could be an effective tool
      for encouraging healthier food choices; however, there is a lack of good-quality
      evidence on this topic. Therefore, the aim of this study was to determine the
      proportions of healthy and unhealthy foods on promotion in Dutch supermarket
      flyers. METHODS: Supermarket food promotions were assessed using the weekly
      promotional flyers of four major Dutch supermarkets over a period of eight weeks.
      All promotions were evaluated for healthiness, price discount, minimum purchase
      amount, product category and promotion type. The level of healthiness consists of
      a 'healthy' group; products which have a positive effect on preventing chronic
      diseases and can be eaten every day. The 'unhealthy' group contain products which
      have adverse effects on the prevention of chronic diseases. Data were analysed
      using ANOVA, independent t-tests and chi-square tests. RESULTS: A total of 1,495
      promotions were included in this study. There were more promotions in the
      unhealthy category; 70% of promotions were categorised as unhealthy. The price
      discount was greater for the healthy promotions (mean 29.5%, SD 12.1) than for
      the two categories of unhealthy promotions (23.7%, SD 10.8; 25.4%, SD 10.5,
      respectively), a tendency which was mainly due to discounts in the fruit and
      vegetables category. To obtain the advertised discount, a significantly higher
      number of products had to be purchased in the unhealthy category than in the
      healthier categories. Promotions in the category meat, poultry and fish category
      occurred frequently. Compared to traditional supermarkets, discounter
      supermarkets had higher percentages of unhealthy food discounts, lower discount
      levels and lower minimum purchase amounts. CONCLUSION: This research confirmed
      that unhealthy foods are more frequently advertised than healthier foods in Dutch
      supermarket flyers. Moreover, consumers had to buy more products to achieve the
      discount when the promotion was categorized as unhealthy, providing extra
      incentive for buying additional unhealthy products. Future research should
      explore the proportion of healthy and unhealthy food discounts in relation to
      supermarkets' total product range, to determine if unhealthy products are over
      represented in promotions or if there are more unhealthy products stocked in
      supermarkets overall. The findings of this study provide an important basis for
      future intervention and policy development aiming to achieve healthier
      supermarket environments.

PMID- 25943990
TI  - Genetic advantageous predisposition of angiotensin converting enzyme id
      polymorphism in Tunisian athletes.
AB  - BACKGROUND: ID polymorphism of the gene coding for the angiotensin I-converting
      enzyme (ACE) represents a determining factor in physical and athletic performance
      in the context of genetic conditioning of sports predisposition. The aim of this
      study was to show the potential importance of genetic factors in relation to the
      athletic status in Tunisian athletes. METHODS: The ACE genotypes were established
      using polymerase chain reaction (PCR) amplification for 282 Tunisian athletes
      (endurance: N.=149 - power: N.=133), and 211 sedentary volunteers. RESULTS: No
      significant difference was found in the ACE genotype distribution between
      athletes (36% DD, 49% ID, 15% II) and controls (CTR) (39% DD, 46% ID, 15% II;
      P=0.72). In contrast, a high significant difference between endurance and power
      groups were noted in genotype and alleles (chi2=10.32, P=0.0057; chi2=4,752,
      P=0.029, respectively). The elite endurance-athletes (N.=72) possess some
      inherent genetic advantage predisposing them to superior athletic performances
      compared to CTR for ACE alleles (chi2=3.51, P=0.06). In addition endurance
      trained athletes were also significantly different from CTR for ACE genotype
      (chi2=6.05, P=0.04). Furthermore, a significant difference have been found
      between elite power-athletes (N.=59) and CTR for ACE alleles (chi2=3.79, P=0.05).
      CONCLUSIONS: Tunisian athletes exhibit insertion (I) and deletion (D) alleles of
      the ACE polymorphism associated with a high level of human endurance and power
      performance, respectively. This genetic background plays an important role in
      sporting potential and causes some individuals to be better adapted to specific
      physical training. This should be considered in athlete development to identify
      which sporting specialties should be trained for Tunisian talent promotion.

PMID- 25943989
TI  - The lycopene beta-cyclase plays a significant role in provitamin A biosynthesis
      in wheat endosperm.
AB  - BACKGROUND: Lycopene beta-cyclase (LCYB) is a key enzyme catalyzing the
      biosynthesis of beta-carotene, the main source of provitamin A. However, there is
      no documented research about this key cyclase gene's function and relationship
      with beta-carotene content in wheat. Therefore, the objectives of this study were
      to clone TaLCYB and characterize its function and relationship with beta-carotene
      biosynthesis in wheat grains. We also aimed to obtain more information about the
      endogenous carotenoid biosynthetic pathway and thus provide experimental support
      for carotenoid metabolic engineering in wheat. RESULTS: In the present study, a
      lycopene beta-cyclase gene, designated TaLCYB, was cloned from the hexaploid
      wheat cultivar Chinese Spring. The cyclization activity of the encoded protein
      was demonstrated by heterologous complementation analysis. The TaLCYB gene was
      expressed differentially in different tissues of wheat. Although TaLCYB had a
      higher expression level in the later stages of grain development, the beta
      carotene content still showed a decreasing tendency. The expression of TaLCYB in
      leaves was dramatically induced by strong light and the beta-carotene content
      variation corresponded with changes of TaLCYB expression. A post-transcriptional
      gene silencing strategy was used to down-regulate the expression of TaLCYB in
      transgenic wheat, resulting in a decrease in the content of beta-carotene and
      lutein, accompanied by the accumulation of lycopene to partly compensate for the
      total carotenoid content. In addition, changes in TaLCYB expression also affected
      the expression of several endogenous carotenogenic genes to varying degrees.
      CONCLUSION: Our results suggest that TaLCYB is a genuine lycopene cyclase gene
      and plays a crucial role in beta-carotene biosynthesis in wheat. Our attempt to
      silence it not only contributes to elucidating the mechanism of carotenoid
      accumulation in wheat but may also help in breeding wheat varieties with high
      provitamin A content through RNA interference (RNAi) to block specific
      carotenogenic genes in the wheat endosperm.

PMID- 25943991
TI  - Feasibility of biohydrogen production from industrial wastes using defined
      microbial co-culture.
AB  - BACKGROUND: The development of clean or novel alternative energy has become a
      global trend that will shape the future of energy. In the present study, 3
      microbial strains with different oxygen requirements, including Clostridium
      acetobutylicum ATCC 824, Enterobacter cloacae ATCC 13047 and Kluyveromyces
      marxianus 15D, were used to construct a hydrogen production system that was
      composed of a mixed aerobic-facultative anaerobic-anaerobic consortium. The
      effects of metal ions, organic acids and carbohydrate substrates on this system
      were analyzed and compared using electrochemical and kinetic assays. It was then
      tested using small-scale experiments to evaluate its ability to convert starch in
      5 L of organic wastewater into hydrogen. For the one-step biohydrogen production
      experiment, H1 medium (nutrient broth and potato dextrose broth) was mixed
      directly with GAM broth to generate H2 medium (H1 medium and GAM broth). Finally,
      Clostridium acetobutylicum ATCC 824, Enterobacter cloacae ATCC 13047 and
      Kluyveromyces marxianus 15D of three species microbial co-culture to produce
      hydrogen under anaerobic conditions. For the two-step biohydrogen production
      experiment, the H1 medium, after cultured the microbial strains Enterobacter
      cloacae ATCC 13047 and Kluyveromyces marxianus 15D, was centrifuged to remove the
      microbial cells and then mixed with GAM broth (H2 medium). Afterward, the
      bacterial strain Clostridium acetobutylicum ATCC 824 was inoculated into the H2
      medium to produce hydrogen by anaerobic fermentation. RESULTS: The experimental
      results demonstrated that the optimum conditions for the small-scale fermentative
      hydrogen production system were at pH 7.0, 35 degrees C, a mixed medium,
      including H1 medium and H2 medium with 0.50 mol/L ferrous chloride, 0.50 mol/L
      magnesium sulfate, 0.50 mol/L potassium chloride, 1% w/v citric acid, 5% w/v
      fructose and 5% w/v glucose. The overall hydrogen production efficiency in the
      shake flask fermentation group was 33.7 mL/h(-1).L(-1), and those the two-step
      and the one-step processes of the small-scale fermentative hydrogen production
      system were 41.2 mL/h(-1).L(-1) and 35.1 mL/h(-1).L(-1), respectively.
      CONCLUSION: Therefore, the results indicate that the hydrogen production
      efficiency of the two-step process is higher than that of the one-step process.

PMID- 25943992
TI  - Comparison of Neutrophil Gelatinase-Associated Lipocalin Versus B-Type
      Natriuretic Peptide and Cystatin C to Predict Early Acute Kidney Injury and
      Outcome in Patients With Acute Heart Failure.
AB  - Neutrophil gelatinase-associated lipocalin (NGAL) has been described in chronic
      heart failure (HF) as marker of tubular damage and renal dysfunction; however,
      less data are available in patients with acute HF. Because of high rate of acute
      kidney injury (AKI) development, we aimed to investigate the role of NGAL in
      predicting early AKI development; second, we compared NGAL with respect to
      cystatin C, B-type natriuretic peptide (BNP), renal function, and blood urea
      nitrogen (BUN) for outcome prediction. We measured admission serum NGAL, cystatin
      C, and BNP in 231 patients affected to acute HF; all patients were submitted to
      daily creatinine, estimated glomerular filtration rate, and measurement to
      identify inhospital AKI defined by Risk, Injury, Failure, Loss, End-Stage Kidney
      Disease and Acute Kidney Injury Network criteria. We also measured admission and
      discharge estimated glomerular filtration rate, creatinine, and BUN to evaluate
      their prognostic role during a 6-month follow-up period; 78 patients developed
      AKI during hospitalization. In these subjects, NGAL levels were significantly
      increased respect to patients without AKI (295 +/- 228 vs 129 +/- 108 ng/ml, p
      <0.001). A cutoff of 134 ng/ml has been related to AKI with good sensibility and
      specificity (85% and 80%, respectively; area under the curve 0.81, p <0.001). BNP
      was also mildly increased (1,000 +/- 906 vs 746 +/- 580 pg/ml, p = 0.03) but not
      cystatin C. Patients with chronic kidney disease demonstrated higher NGAL levels
      compared with subjects with preserved renal function (258 +/- 249 and 120 +/- 77
      ng/ml, p <0.001). The receiver-operating characteristic curve analysis
      demonstrated that increased NGAL values were associated with increased mortality
      (cutoff 170 ng/ml, sensibility 60%, specificity 82%, accuracy 71%, area under the
      curve 0.77, p <0.001). The same significant correlation was also found for BUN at
      discharge (cutoff 100 mg/dl, sensibility 65%, specificity 85%, accuracy 71%, area
      under the curve 0.77, p <0.001). Multivariable Cox regression analysis showed
      that cutoff 170 ng/ml was related with adverse outcome (hazard ratio 1.77,
      confidence interval 1.24 to 2.83, p = 0.01). In conclusion, NGAL measurement is a
      sensible tool to predict AKI during hospitalization. Elevated NGAL levels appear
      to be related to BUN increase and post-discharge outcome. This suggests a
      prognostic role of tubular damage beyond renal dysfunction.

PMID- 25943994
TI  - Certification: value-added care.

PMID- 25943993
TI  - Mechanism study of peptide GMBP1 and its receptor GRP78 in modulating gastric
      cancer MDR by iTRAQ-based proteomic analysis.
AB  - BACKGROUND: Multidrug resistance (MDR) is a major obstacle to the treatment of
      gastric cancer (GC). Using a phage display approach, we previously obtained the
      peptide GMBP1, which specifically binds to the surface of MDR gastric cancer
      cells and is subsequently internalized. Furthermore, GMBP1 was shown to have the
      potential to reverse the MDR phenotype of gastric cancer cells, and GRP78 was
      identified as the receptor for this peptide. The present study aimed to
      investigate the mechanism of peptide GMBP1 and its receptor GRP78 in modulating
      gastric cancer MDR. METHODS: Fluorescence-activated cell sorting (FACS) and
      immunofluorescence staining were used to investigate the subcellular location and
      mechanism of GMBP1 internalization. iTRAQ was used to identify the MDR-associated
      downstream targets of GMBP1. Differentially expressed proteins were identified in
      GMBP1-treated compared to untreated SGC7901/ADR and SGC7901/VCR cells. GO and
      KEGG pathway analyses of the differentially expressed proteins revealed the
      interconnection of these proteins, the majority of which are involved in MDR. Two
      differentially expressed proteins were selected and validated by western
      blotting. RESULTS: GMBP1 and its receptor GRP78 were found to be localized in the
      cytoplasm of GC cells, and GRP78 can mediate the internalization of GMBP1 into
      MDR cells through the transferrin-related pathway. In total, 3,752 and 3,749
      proteins were affected in GMBP1-treated SGC7901/ADR and SGC7901/VCR cells,
      respectively, involving 38 and 79 KEGG pathways. Two differentially expressed
      proteins, CTBP2 and EIF4E, were selected and validated by western blotting.
      CONCLUSION: This study explored the role and downstream mechanism of GMBP1 in GC
      MDR, providing insight into the role of endoplasmic reticulum stress protein
      GRP78 in the MDR of cancer cells.

PMID- 25943995
TI  - Fatigue in Parkinson disease: an integrative review.
AB  - Fatigue, one of the most prevalent and underassessed nonmotor symptoms in
      patients with Parkinson disease (PD), is reported to be a major cause of
      disability and reduced quality of life. The purpose of this review was to
      systematically examine the scientific literature and report how fatigue is
      defined and measured and what interventions are used to treat it. A synthesis of
      the current literature will expose the current state of the science of fatigue in
      PD, propose areas for future research, and offer practice implications. An
      integrative review of the literature was conducted. The electronic databases
      CINAHL, Psychinfo, and PUBMED were searched using the keywords "Parkinson's
      disease," "fatigue," "definition," "mental fatigue," "physical fatigue,"
      "measurement," "interventions," "treatment," and "methylphenidate." One hundred
      fourteen articles were found. Nineteen studies met review criteria. No universal
      definition of fatigue in PD was found, making it difficult to measure. However,
      central, physical, mental, and peripheral fatigues were described. Six scales
      were found that measure fatigue in PD; only one specific to PD, the Parkinson
      Fatigue Scale, measured physical fatigue. Seven studies reported interventions to
      treat fatigue and were categorized as medication, exercise, and alternative
      interventions. None of these interventions had a significant effect on fatigue.
      Findings showed that (a) there is a lack of a universally accepted definition of
      fatigue because of its subjective nature, (b) existing fatigue measurement tools
      do not measure all types of fatigue in PD, and (c) no intervention had a
      significant effect on fatigue. There is a need to define and explore fatigue
      further using qualitative methods. Further development of instruments to measure
      fatigue in women, younger onset, and older adults with PD is needed. A focus on
      person-centered interventions to reduce fatigue in patients with PD is a research
      priority. 

PMID- 25943996
TI  - Commentary on "patient perspectives of barriers and facilitators of treatment
      seeking behaviors for stroke care".

PMID- 25943997
TI  - Myasthenia gravis: a careful perioperative anesthetic management of coronary
      artery bypass grafting.
AB  - Nowadays, even hazardous cardiac surgery can be performed on patients with
      autoimmune diseases like myasthenia gravis. It requires a sensitive perioperative
      anesthetic approach especially in relation to nondepolarizing muscle relaxant
      administration. Myasthenic patients produce antibodies against the end-plate
      acetylcholine receptors causing muscle weakness and sensitivity to
      nondepolarizing muscle relaxants that could lead to respiratory failure.
      Perioperative nurse care is critical for uncomplicated course of treatment;
      therefore, apprehension of surgical procedure should be helpful on an everyday
      basis. We describe successful management without any pulmonary complications of
      two patients with myasthenia gravis undergoing coronary artery bypass grafting.
      In addition, antiacetylcholine receptor antibodies concentrations were evaluated
      during treatment time. In conclusion, we have found that reduced titrated doses
      of cisatracurium may be safely used in patients with myasthenia gravis undergoing
      cardiac surgery without anesthesia and respiratory-related complications. 

PMID- 25943998
TI  - An exploratory study of the bilateral bispectral index for pain detection in
      traumatic-brain-injured patients with altered level of consciousness.
AB  - INTRODUCTION: Many patients with a traumatic brain injury (TBI) cannot
      communicate because of altered level of consciousness. Although observation of
      pain behaviors (e.g., frowning) is recommended for pain assessment in nonverbal
      populations, they are attenuated and sometimes even suppressed in patients with
      TBI receiving high doses of sedatives. This study explored the potential utility
      of the bilateral bispectral index system (BIS) for pain detection in critically
      ill adults with TBI and altered level of consciousness. METHODS: Using a repeated
      measure within-subject design, participants (N = 25) were observed for 1 minute
      before (baseline), during, and 15 minutes after two procedures: (a) noninvasive
      blood pressure (nonnociceptive) and (b) turning (nociceptive). At each
      assessment, BIS indexes (0-100) of the right (R) and left (L) hemispheres and
      pain behaviors were documented. RESULTS: Compared with baseline, significant
      median increases (p <= .05) in BIS-R (+4.93%) and BIS-L (+8.43%) and in the
      frequency of pain behaviors (+3.00) were observed during turning but not
      noninvasive blood pressure. Interestingly, increases in BIS-R were more
      pronounced in participants with left-sided TBI (+17.23%, p = .021) than those
      with right-sided TBI (+3.01%). BIS-R fluctuations in participants with left-sided
      TBI were also positively correlated (r(s) = .986, p <= .001) with the frequency
      of pain behaviors observed during turning. CONCLUSIONS: Overall, only increases
      in BIS-R were correlated with participants' pain behaviors and in those with left
      sided TBI exclusively. Although further research is needed, our findings support
      the potential use of the bilateral BIS for pain detection in nonverbal patients
      with TBI who cannot behaviorally respond to pain, but only when they have a left
      sided injury.

PMID- 25943999
TI  - Memory training plus yoga for older adults.
AB  - Previous tests of the SeniorWISE intervention with community-residing older
      adults that were designed to improve affect and cognitive performance were
      successful and positively affected these outcomes. In this study, we tested
      whether adding yoga to the intervention would affect the outcomes. Using a
      quasiexperimental pre-post design, we delivered 12 hours of SeniorWISE memory
      training that included a 30-minute yoga component before each training session.
      The intervention was based on the four components of self-efficacy theory:
      enactive mastery experience, vicarious experience, verbal persuasion, and
      physiologic arousal. We recruited 133 older adults between the ages of 53 and 96
      years from four retirement communities in Central Texas. Individuals were
      screened and tested and then attended training sessions two times a week over 4
      weeks. A septuagenarian licensed psychologist taught the memory training, and a
      certified yoga instructor taught yoga. Eighty-three participants completed at
      least 9 hours (75%) of the training and completed the posttest. Those individuals
      who completed made significant gains in memory performance, instrumental
      activities of daily living, and memory self-efficacy and had fewer depressive
      symptoms. Thirteen individuals advanced from poor to normal memory performance,
      and seven improved from impaired to poor memory performance; thus, 20 individuals
      improved enough to advance to a higher functioning memory group. The findings
      from this study of a memory training intervention plus yoga training show that
      the benefits of multifactorial interventions had additive benefits. The combined
      treatments offer a unique model for brain health programs and the promotion of
      nonpharmacological treatment with the goals of maintaining healthy brain function
      and boosting brain plasticity. 

PMID- 25944001
TI  - Spinal-Cord-Injured Individual's Experiences of Having a Partner: A
      Phenomenological-Hermeneutic Study.
AB  - Having a partner is a strong factor in adaptation to the new life situation with
      a spinal cord injury (SCI). Still, more knowledge in detail about the partner's
      influences according to the experiences of individuals with SCI could contribute
      to the understanding of the situation after an injury. The aim of this
      phenomenological-hermeneutic article is to achieve a deeper understanding of nine
      individuals' experiences the first 2 years after SCI. In rehabilitation after
      SCI, the partner supported the SCI individual's life spirit by not giving up and
      by still seeing possibilities in the future. The partner reinforced the SCI
      individual's commitment to life by sharing experiences; providing love, trust,
      and hope; and giving priority to the best things in life for the SCI individual.
      This implied cohabitation providing concrete help and an intimacy that helped to
      cope with problems and anxieties and allowed SCI individuals the ability to self
      realize. This promoted feelings of profound gratitude but also dependency. Thus,
      the SCI individual benefitted from the partner's support mentally and physically,
      which enabled a life that would not otherwise be possible. 

PMID- 25944002
TI  - Measuring workload of nurses on a neurosurgical care unit.
AB  - AIM OF THE STUDY: The aim of this study was to create a model of workload that
      could be used to manage workload and increase satisfaction of workload for nurses
      on a neuroscience care unit. BACKGROUND: No study was found that delineated a
      model of workload that could be used to manage or improve satisfaction with
      workload for a neuroscience care unit at either the individual nurse or unit
      level. METHODS: Staff, management, and a researcher collaboratively developed a
      model to examine workload on a neuroscience care unit. Forty-three independent
      variables of workload and the dependent variable of satisfaction with workload
      were studied over 28 days using stepwise regression. Stepwise regression is
      appropriate for model building. Criteria to enter any independent variable into a
      regression equation included correlating with the dependent variable of
      satisfaction with workload, validation of central tendency assumptions, and good
      data fit using residual diagnostics. RESULTS: Independent variables of workload
      that explained the variance of satisfaction with workload included time (15.9%),
      undelegated work (4.0%), number of isolation patients (2.9%), individual
      employees (2.1%), number of patients (1.3%), and number of postoperative
      neurosurgical patients (1.1%). On the unit level, satisfaction with workload was
      predicted by time (42.5%) and the number of nurses on duty (7.7%). CONCLUSIONS:
      Satisfaction with workload as reported by staff nurses is predicted by both
      individual- and unit-level factors of workload. Staff input is crucial to the
      development of a model of workload on clinical specialty units like neuroscience
      care. Staff nurses identify key variables, otherwise overlooked, affecting
      workload and satisfaction and satisfaction with workload. IMPLICATIONS FOR
      NURSING MANAGEMENT: It is vital to develop unit-specific models of workload and
      consider both individual- and unit-level factors. Such models have potential for
      deeper research into both management and increasing satisfaction of workload at
      the level of clinical specialty/unit.

PMID- 25944003
TI  - Novel metronomic chemotherapy and cancer vaccine combinatorial strategy for
      hepatocellular carcinoma in a mouse model.
AB  - Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and
      represents the third and the fifth leading cause of cancer-related death
      worldwide in men and women, respectively. Hepatitis B virus (HBV) and hepatitis C
      virus (HCV) chronic infections account for pathogenesis of more than 80 % of
      primary HCC. HCC prognosis greatly varies according to stage at beginning of
      treatment, but the overall 5-year survival rate is approximately 5-6 %. Given the
      limited number of effective therapeutic strategies available, immunotherapies and
      therapeutic cancer vaccines may help in improving the clinical outcome for HCC
      patients. However, the few clinical trials conducted to date have shown
      contrasting results, indicating the need for improvements. In the present study,
      a novel combinatorial strategy, based on metronomic chemotherapy plus vaccine, is
      evaluated in a mouse model. The chemotherapy is a multi-drug cocktail including
      taxanes and alkylating agents, which is administered in a metronomic-like
      fashion. The vaccine is a multi-peptide cocktail including HCV as well as
      universal tumor antigen TERT epitopes. The combinatorial strategy designed and
      evaluated in the present study induces an enhanced specific T cell response, when
      compared to vaccine alone, which correlates to a reduced Treg frequency. Such
      results are highly promising and may pave way to relevant improvements in
      immunotherapeutic strategies for HCC and beyond.

PMID- 25944004
TI  - "Cancer Bio-Immunotherapy in Siena": Twelfth Meeting of the Network Italiano per
      la Bioterapia dei Tumori (NIBIT), Siena, Italy, October 9-11, 2014.

PMID- 25944005
TI  - CD163+CD14+ macrophages, a potential immune biomarker for malignant pleural
      effusion.
AB  - BACKGROUND: Malignant pleural effusion (MPE) is a common complication caused by
      malignant diseases. However, subjectivity, poor sensitivity, and substantial
      false-negative rates of cytology assay hamper accurate MPE diagnosis. The aim of
      this study was to assess whether CD163+CD14+ tumor-associated macrophages (TAMs)
      could be used as a biomarker for enabling sensitive and specific MPE diagnosis.
      METHODS: Pleural effusion samples and peripheral blood samples were collected
      from 50 MPE patients and 50 non-malignant pleural effusion (NMPE) patients,
      respectively. Flow cytometry was performed to analyze cell phenotypes, and RT
      qPCR was used to detect cytokine expression in these monocytes and macrophages. A
      blinded validation study (n = 40) was subsequently performed to confirm the
      significance of CD163+CD14+ TAMs in MPE diagnosis. Student's t test, rank sum
      test, and receiver operating characteristic curve analysis were used for
      statistical analysis. RESULTS: Notably, CD163+CD14+ cell frequency in MPE was
      remarkably higher than that in NMPE (P < 0.001). In a blinded validation study, a
      sensitivity of 78.9 % and a specificity of 100 % were obtained with CD163+CD14+
      TAMs as a MPE biomarker. In total (n = 140), by using a cutoff level of 3.65 %,
      CD163+CD14+ cells had a sensitivity of 81.2 % and a specificity of 100 % for MPE
      diagnosis. Notably, MPE diagnosis by estimating CD163+CD14+ cells in pleural
      effusion could be obtained one week earlier than that obtained by cytological
      examination. CONCLUSIONS: CD163+CD14+ macrophages could be potentially used as an
      immune diagnostic marker for MPE and has better assay sensitivity than that of
      cytological analysis.

PMID- 25944006
TI  - Effect of Extended pi Conjugation on the Spectroscopic and Electrochemical
      Properties of Boron Difluoride Formazanate Complexes.
AB  - The effect of extended pi conjugation on the spectroscopic and electrochemical
      properties of boron difluoride (BF2) formazanate complexes was studied by the
      systematic comparison of phenyl- and naphthyl-substituted derivatives. Each of
      the BF2 complexes described was characterized by (1)H, (13)C, (11)B, and (19)F
      NMR spectroscopy, cyclic voltammetry, infrared spectroscopy, UV-vis absorption
      and emission spectroscopy, and mass spectrometry. X-ray crystallography and
      electronic structure calculations were used to rationalize the trends observed,
      including direct comparison of 3-cyano-, 3-nitro-, and 3-phenyl-substituted BF2
      formazanate complexes. In all cases, the wavelengths of maximum absorption and
      emission were red-shifted as pi conjugation was systematically extended (by
      replacing phenyl with naphthyl), fluorescence quantum yields increased (up to 10
      fold), and electrochemical conversion of the formazanate complexes to their
      radical anion and dianion forms occurred at less negative potentials (easier to
      reduce). 

PMID- 25944007
TI  - Antinociceptive and anti-inflammatory activities of Schefflera octophylla
      extracts.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Schefflera octophylla (Lour.) Harms, a
      traditional Chinese herb mainly distributed in Southeast Asia, is extensively
      prescribed to alleviate pain and treat rheumatoid arthritis (RA), influenza,
      throat swelling, pain, etc. In this paper, the antinociceptive and anti
      inflammatory activities of the ethanol extract and its five different polar
      fractions of this plant were evaluated. Furthermore, the anti-rheumatoid
      arthritis activity of the ethanol extract and its active fraction (CHCl3
      fraction) were evaluated. And the chemical constituents of the CHCl3 active
      fraction displayed significant antinociceptive and anti-inflammatory activities
      were investigated. MATERIALS AND METHODS: Antinociceptive and anti-inflammatory
      activities were investigated by hot plate test, acetic acid-induced abdominal
      writhing test and formalin test, xylene-induced ear edema test. The anti
      rheumatoid arthritis activity was evaluated through the model of adjuvant-induced
      arthritis (AA) in rats, paw swelling, pain response, arthritis index and
      histopathological changes of ankle, the levels of TNF-alpha, IL-1beta, IL-6 and
      rheumatoid factor (RF) of rats were detected. The chemical constituents of the
      CHCl3 fraction were isolated using chromatographic techniques. Their structures
      were elucidated by spectroscopic data analysis. RESULTS: The results showed that
      the ethanol extract of S. octophylla has significant dose-dependent anti
      inflammatory and antinociceptive activities. And its five different polar
      fractions especially the CHCl3 fraction significantly inhibited the abdominal
      writhing induced by acetic acid and ear edema induced by xylene, also increased
      pain threshold in hot plate test in 120 min and reduced ticking times in formalin
      test. The ethanol extract of S. octophylla and the CHCl3 fraction demonstrated an
      anti-RA effect in a dose-dependent manner. The levels of TNF-alpha, IL-1beta and
      IL-6 in ethanol extract (600 mg/kg) and CHCl3 fraction (300 mg/kg) groups were
      significantly lower than those of the model group. The chemical constituents
      study of the CHCl3 fraction from S. octophylla led to six triterpenoids which
      were identified as taraxerone (1), 3-epi-taraxerol (2), aleuritolic acid (3), 3
      oxofriedelan-28-oic acid (4), 3beta,19alpha -dihydroxy-urs-12-ene- 24,28-dioic
      acid (5) and asiatic acid (6). Compounds 1-5 were obtained from this plant for
      the first time. CONCLUSION: This study proved the antinociceptive, anti
      inflammatory and anti-rheumatoid arthritis activities of S. octophylla.
      Triterpenoids obtained from its CHCl3 fraction may be responsible for those
      activities. These results could support the fact that S. octophylla is used
      traditionally to cure inflammatory and pain diseases.

PMID- 25944008
TI  - Medicinal plants of the Kamiesberg, Namaqualand, South Africa.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Qualitative and quantitative data is presented
      that gives a new perspective on the traditional medicinal plants of the Khoisan
      (Khoe-San), one of the most ancient of human cultures. The data is not only of
      considerable historical and cultural value, but allows for fascinating
      comparative studies relating to new species records, novel use records and the
      spatial distribution of traditional plant use knowledge within the Cape Floristic
      Region. AIM OF THE STUDY: A detailed documentation and quantitative analysis of
      medicinal plants of the Kamiesberg area (an important Khoisan and Nama cultural
      centre) and their traditional uses, which have hitherto remained unrecorded.
      MATERIALS AND METHODS: During four study visits to the Kamiesberg, semi
      structured and structured interviews were conducted with 24 local inhabitants of
      the Kamiesberg, mostly of Khoisan decent. In addition to standard methodology, a
      newly developed Matrix Method was used to quantity medicinal plant knowledge.
      RESULTS: The Kamiesberg is an important center of extant Nama ethnomedicinal
      information but the knowledge is rapidly disappearing. Of a total of 101
      medicinal plants and 1375 anecdotes, 21 species were recorded for the first time
      as having traditional medicinal uses and at least 284 medicinal use records were
      new. The relative importance, popularity and uses of the plants were quantified.
      The 97 newly documented vernacular names include 23 Nama (Khoekhoegowab) names
      and an additional 55 new variations of known names. The calculated Ethnobotanical
      Knowledge Index (EKI) and other indices accurately quantified the level of
      knowledge and will allow for future local, regional and even global comparisons.
      CONCLUSION: The results showed that the Kamiesberg is an important focal point of
      Khoisan (Nama) traditional knowledge but that the medicinal plants have not yet
      been systematically recorded in the scientific literature. There are numerous new
      use records and new species records that are in need of scientific study.
      Comparative data is now available for broader comparisons of the pattern of
      Khoisan plants use in southern Africa and the study represents another step
      towards a complete synthesis of Cape Herbal Medicine.

PMID- 25944009
TI  - Improvement in oral bioavailability and dissolution of tanshinone IIA by
      preparation of solid dispersions with porous silica.
AB  - OBJECTIVES: This study aims to evaluate the oral bioavailability and dissolution
      of tanshinone IIA (tanIIA) by preparation of solid dispersions (SDs) with porous
      silica. METHODS: SDs of tanIIA were prepared using a solvent method. The
      physicochemical properties, dissolution property, drug stability and in-vivo
      performance of the SDs prepared were all evaluated. KEY FINDINGS: Compared with
      tanIIA alone and corresponding physical mixtures, tanIIA from SDs showed
      remarkably improved in-vitro dissolution rate. After forming the SDs, tanIIA
      changed into an amorphous state, which can infer from differential scanning
      calorimetry (DSC) and X-ray powder diffraction (XRPD). Fourier transform infrared
      spectroscopy (FTIR) also revealed the presence of interactions between tanIIA and
      porous silica in SDs. During the stability study, there is no significant
      decreasing in either the in-vitro dissolution or the drug content, which was
      observed following storage at room temperature for 12 months. The results of a
      pharmacokinetic study in rats showed the areas under the concentration-time curve
      from 0 h to 24 h (AUC0-24h ) for the SDs and tanIIA were 1019.87 +/- 161.819 mg/h
      per litre and 343.70 +/- 75.628 mg/h per litre, respectively. CONCLUSIONS: SDs
      with porous silica as carrier could achieve superior oral bioavailability by
      improving drug dissolution, whereas drug stability could be maintained.

PMID- 25944010
TI  - Antioxidants as a Potential Preventive and Therapeutic Strategy for Cadmium.
AB  - Epidemiological studies provide a growing number of evidences that chronic
      exposure to relatively low levels of cadmium (Cd), nowadays taking place in
      industrialized countries, may cause health hazard. Thus, growing interest has
      been focused on effective ways of protection from adverse effects of exposure to
      this heavy metal. Because numerous effects to Cd's toxic action result from its
      prooxidative properties, it seems reasonable that special attention should be
      directed to agents that can prevent or reduce this metal-induced oxidative stress
      and its consequences in tissues, organs and systems at risk of toxicity,
      including liver, kidneys, testes, ears, eyes, cardiovascular system and nervous
      system as well as bone tissue. This review discusses a wide range of natural
      (plant and animal origin) and synthetic antioxidants together with many plant
      extracts (e.g. black and green tea, Aronia melanocarpa, Allium sativum, Allium
      cepa, Ocimum sanctum, Phoenix dactylifera, Physalis peruviana, Zingiber
      officinale) that have been shown to prevent from Cd toxicity. Moreover, some
      attention has been focused on the fact that substances not possessing
      antioxidative potential may also prevent Cd-induced oxidative stress and its
      consequences. So far, most of the data on the protective effects of the natural
      and synthetic antioxidants and plant extracts come from studies in animals'
      models; however, numerous of them seem to be promising preventive/therapeutic
      strategies for Cd toxicity in humans. Further investigation of prophylactic and
      therapeutic use of antioxidants in populations exposed to Cd environmentally and
      occupationally is warranted, given that therapeutically effective chelation
      therapy for this toxic metal is currently lacking.

PMID- 25944011
TI  - Targeting the Noradrenergic System in Posttraumatic Stress Disorder: A Systematic
      Review and Meta-Analysis of Prazosin Trials.
AB  - Post-traumatic stress disorder (PTSD) is a chronic psychiatric disorder that may
      develop after exposure to a life-threatening trauma. As veterans and armed forces
      may deal with diverse health problems compared with civilians, they have a
      greater risk for psychiatric disorders, including PTSD, than civilians, even if
      the disorder may be also frequent in the general population. PTSD is associated
      with significant comorbidity, especially with mood disorders and substance abuse.
      Moreover, the suicide risk is higher in PTSD patients than in the general
      population. Selective Serotonin Reuptake Inhibitors (SSRIs), atypical
      antipsychotics and benzodiazepines are commonly employed in the management of
      PTSD, but often these treatments fail or are discontinued due to adverse effects.
      It has been demonstrated that high noradrenergic activity may be associated with
      hyperarousal, trauma nightmares and sleep disturbances in PTSD subjects, probably
      through the stimulation of alpha -1 adrenergic receptors in the brain prefrontal
      cortex. The alpha -1 adrenoreceptor antagonist prazosin decreases noradrenaline
      effects at brain alpha-1 adrenoreceptors and may be a promising agent in the
      treatment of PTSD, as some studies have found it effective and well tolerated.
      Therefore, the present review is aimed to examine the role of noradrenergic
      system in the pathophysiology of PTSD. Moreover, we conducted a systematic review
      to evaluate the effectiveness and tolerability of prazosin in PTSD patients. Meta
      analysis was used to combine data from multiple studies and better estimate the
      effect of prazosin on specific outcomes. We found prazosin to be significantly
      more efficacious than placebo in reducing distressing dreams in PTSD patients,
      even though our results should be interpreted with caution due to the small
      number of studies included in our quantitative synthesis. 

PMID- 25944012
TI  - Redox-Related Mechanisms to Rebalance Cancer-Deregulated Cell Growth.
AB  - A delicate balance exists between the process of carcinogenesis and tissue
      regeneration. A number of malignant tumours are considered the outcome of an
      impaired or incomplete regeneration process, resulting in persistently dividing
      cells. Regeneration-competent tissues and animals are able to prevent and
      counteract growth abnormalities and seem to have a low vulnerability to chemical
      carcinogenesis. Cancer cell survival depends, among other things, on various
      redox-related mechanisms, which are targets of currently developed therapies.
      Disadvantages of these therapies are a lack of specificity and drug resistance.
      As the majority of these redox-related mechanisms also play an important role in
      successful and coordinated cell functioning and reproduction, the regeneration
      process offers a unique parallel context for modern cancer research. This review
      focuses on the interconnections between regeneration and carcinogenesis and how
      an understanding of regenerative forces and redox-controlled mechanisms could
      contribute to the identification of new therapeutic targets to block the growth
      and survival of cancer cells.

PMID- 25944013
TI  - Gastric Carcinoma at the Era of Targeted Therapies.
AB  - Gastric and gastro-esophageal cancers (GC/GEJ) appear as the second cancer
      related death worldwide. Diagnosis is made at an advanced stage offering a
      curative attempt in less than 50% of cases. Despite the improvements of the
      systemic cytotoxic chemotherapy regimens, the prognosis of patients with
      metastatic GC/GEJ cancer remains poor. Recent insights in biochemical pathways
      have permitted to identify potential targets. The extracellular domain of HER2
      receptors is implicated in cells' proliferation and in the anti-apoptotic process
      occurring in GC/GEJ cancers. Trastuzumab, a monoclonal antibody targeting HER2,
      in addition to chemotherapy permitted to obtain more than one year of survival in
      HER2-positive advanced GC/GEJ cancers. Recently, ramucirumab, a humanized
      monoclonal antibody targeting VEGFR-2 receptor demonstrated its efficacy as a
      second line treatment for patients with advanced GC/GEJ cancer. These encouraging
      results have justified evaluating targeted therapies in GC/GEJ cancers. In this
      review, we summarize targeted therapies that might present clinical efficacy in
      the treatment of advanced GC/GEJ cancers.

PMID- 25944014
TI  - Current Perspectives on Novel Drug Delivery Systems and Approaches for Management
      of Cervical Cancer: A Comprehensive Review.
AB  - Cervical cancer is uterine cervix carcinoma, the second deadly cancer and has a
      high incidence and mortality rate. In the developing world conventional treatment
      strategies such as surgical intervention and chemoradiotherapy are less widely
      available. Currently cancer research focuses on improving treatment of cervical
      cancer using various therapies such as gene therapy, recombinant protein therapy,
      photodynamic therapy, photothermal therapy and delivery of chemotherapeutic
      agents using nanoparticles, hydrogel and liposomal based delivery systems and
      also localized delivery systems which exist in a variety of forms such as
      intravaginal rings, intravaginal patches, intravaginal films, etc. in order to
      improve the drug delivery in a controlled manner to the diseased site thereby
      reducing systemic side effects. The present review encloses existing diverse
      delivery systems and approaches intended for treatment of cervical cancer. 

PMID- 25944015
TI  - Interfering with Hedgehog Pathway: New Avenues for Targeted Therapy in
      Rhabdomyosarcoma.
AB  - Rhabdomyosarcoma (RMS) is the most frequent pediatric soft-tissue tumor
      accounting for about 7% of childhood malignancies. Multimodal therapy is the
      standard treatment for individuals with RMS but generally fails to cure high-risk
      group patients and can result in long-term side effects. Therefore, understanding
      the mechanisms driving RMS might help to find new candidate targets for more
      specific and effective therapeutic modalities. One of the molecular machineries
      which is often deregulated in cancer and specifically involved in tumorigenesis
      of RMS, is Hedgehog (Hh) signaling. There is increasing evidence that targeting
      this developmental pathway may hold promise in future treatment strategies for
      RMS. In this review, we discuss the contribution of the Hh pathway in RMS, the
      challenges of inhibiting this embryonic signaling in children with an update on
      recent preclinical data and ongoing clinical trials.

PMID- 25944016
TI  - A Review of Pharmacological Treatment Options for Lung Cancer: Emphasis on Novel
      Nanotherapeutics and Associated Toxicity.
AB  - Lung cancer remains a leading cause of death. Current treatment options are
      generally ineffective, highlighting the dire need for novel approaches. While
      numerous biologically-active chemotherapeutics have been discovered in the last
      two decades, biological barriers including minimal water solubility, stability,
      and cellular resistance hinder in vivo effectiveness. To overcome these
      limitations, nanoparticles have been designed to deliver chemotherapeutics
      selectively to cancerous tissue while minimizing pharmacokinetics hindrance.
      Numerous studies are underway analyzing the efficacy of nanoparticles in drug
      delivery, theranostic applications, and photothermal therapy. However, while
      nanoparticles have shown efficacy in treating some cancers, their potential
      toxicity and lack of targeting may hinder clinical potential. With the aim to
      help sort through these issues, we conduct a review to describe recent
      applications of nanotherapeutics for the treatment and diagnosis of lung cancer.
      We first provide a detailed background of statistics, etiology, histological
      classification, staging, diagnosis, and current treatment options. This is
      followed by a description of current applications of nanotherapeutics, focusing
      primarily on results published during the past five years. The potential toxicity
      associated with nanoparticles is evaluated, revealing inconclusive information
      which highlights the need for further studies. Lastly, recent advances in
      mathematical modeling and computational simulation have shown potential in
      predicting tumor response to nanotherapeutics. Thus, although nanoparticles have
      shown promise in treating lung cancer, further multi-disciplinary studies to
      quantify optimal dosages and assess possible toxicity are still needed. To this
      end, nanotherapeutic options currently in clinical trials offer hope to help
      address some of these critical issues. 

PMID- 25944017
TI  - Gene therapy for inherited blindness disorder improves eyesight in short term,
      study shows.

PMID- 25944018
TI  - Paprika rhinoconjunctivitis case reveals new occupational Capsicum allergens.
AB  - No allergens related to paprika or cayenne respiratory allergy have been
      identified thus far. We describe a previously healthy 28-year woman who developed
      work-related rhinoconjunctivitis after four years of kebab-restaurant work. The
      allergy was studied using skin prick tests, serum specific IgE and nasal
      provocation tests. Specific IgE protein reactions were studied by Western blot
      analysis. Paprika, cayenne and curry allergens were identified from the strongest
      immunoblot bands using tandem mass spectrometry. A positive skin prick test, high
      specific IgE and positive nasal provocation test confirmed occupational
      rhinoconjunctivitis from Capsicum spices. Defensin J1 and Vicilin were identified
      as major paprika and cayenne allergens in this case. Vicilin was detected also
      from the curry ingredients. Two new occupational respiratory allergens from the
      Capsicum species were identified. These differ from previously reported bell
      pepper allergens. We emphasize that substantial spice handling at work poses an
      allergy risk.

PMID- 25944019
TI  - Adherence to Metformin, Statins, and ACE/ARBs Within the Diabetes Health Plan
      (DHP).
AB  - BACKGROUND: Reducing patient cost-sharing and engaging patients in disease
      management activities have been shown to increase uptake of evidence-based care.
      OBJECTIVE: To evaluate the effect of employer purchase of a disease-specific plan
      with reduced cost-sharing and disease management (the Diabetes Health Plan/DHP)
      on medication adherence among eligible employees and dependents. DESIGN: Employer
      level "intent to treat" cohort study, including data from eligible employees and
      their dependents with diabetes, regardless of whether they were enrolled in the
      DHP. SETTING: Employers that contracted with a large national health plan
      administrator in 2009, 2010, and/or 2011. PARTICIPANTS: Ten employers that
      purchased the DHP and 191 employers that did not (controls). Inverse probability
      weighting (IPW) estimation was used to adjust for inter-group differences.
      INTERVENTION: The DHP includes free or low-cost medications and physician visits.
      Enrollment strategies and specific benefit designs are determined by the employer
      and vary in practice. DHP participants are notified up front that they must
      engage in their own health care (e.g., receiving diabetes-related screening) in
      order to remain enrolled. MAIN OUTCOME MEASURE: Mean employee adherence to
      metformin, statins, and ACE/ARBs at the employer level at one year post-DHP
      implementation, as measured by the proportion of days covered (PDC). RESULTS:
      Baseline adherence to the three medications was similar across DHP and control
      employers, ranging from 64 to 69 %. In the first year after DHP implementation,
      predicted employer-level adherence for metformin (+4.9 percentage points, p =
      0.017), statins (+4.8, p = 0.019), and ACE/ARBs (+4.4, p = 0.02) was higher with
      DHP purchase. LIMITATIONS: Non-randomized, observational study. CONCLUSIONS: The
      Diabetes Health Plan, an innovative health plan that combines reduced cost
      sharing and disease management with an up-front requirement of enrollee
      participation in his or her own health care, is associated with a modest
      improvement in medication adherence at 12 months.

PMID- 25944020
TI  - Patient Preferences for Test Result Notification.
AB  - IMPORTANCE: Patients are increasingly being given access to their test results,
      but little is known about how preferences vary with the test under consideration
      or the results of the test (normal or abnormal). OBJECTIVE: This study was
      conducted to examine preferences for test result communication. DESIGN, SETTING,
      AND PARTICIPANTS: We surveyed adults to explore their preferences for test result
      notification for three common diagnostic tests of varying "emotional impact"
      (dual-energy x-ray absorptiometry [DXA], genital herpes, and cancer biopsy) when
      test results were 1) normal and 2) abnormal. We conducted our survey between June
      and August 2012 on the campus of an academic medical center. For each scenario,
      subjects were asked to rank seven methods that might be used to communicate test
      results (letter, unsecured email, secured email, text message, telephone call,
      secure Web portal, office visit) in order of acceptability. MAIN OUTCOME
      MEASURES: The main measures were the percentage of respondents who ranked a
      particular test result notification method favorably and the percentage who
      ranked it as unacceptable. RESULTS: When test results were normal, subjects'
      notification preferences were generally similar for DXA, herpes and cancer
      biopsy, with telephone and letter ranked most favorably for all three tests.
      Conversely, text message and unsecured email were viewed as unacceptable
      notification methods for normal results by 45.0-55.0 % of subjects across all
      three tests. When test results were abnormal, office visits became more popular.
      A higher proportion of subjects ranked office visits as their most preferred
      notification method for our test with high "emotional impact" (cancer biopsy)
      (38.4 %) as compared to DXA (28.2 %) and herpes (27.9 %) (P = 0.02). For most
      test scenarios, younger subjects appeared to rank electronic communication
      modalities (secure email or Web portal) higher than older subjects, though this
      difference did not reach statistical significance (P = 0.29). CONCLUSIONS:
      Preferences for test result notification can differ substantially depending upon
      the test under consideration and results of the test. Providers and health care
      systems should consider these factors when deciding how to communicate results to
      patients.

PMID- 25944021
TI  - Development of a novel cell sorting method that samples population diversity in
      flow cytometry.
AB  - Flow cytometry based electrostatic cell sorting is an important tool in the
      separation of cell populations. Existing instruments can sort single cells into
      multi-well collection plates, and keep track of cell of origin and sorted well
      location. However currently single sorted cell results reflect the population
      distribution and fail to capture the population diversity. Software was designed
      that implements a novel sorting approach, "Slice and Dice Sorting," that links a
      graphical representation of a multi-well plate to logic that ensures that single
      cells are sampled and sorted from all areas defined by the sort region/s.
      Therefore the diversity of the total population is captured, and the more
      frequently occurring or rarer cell types are all sampled. The sorting approach
      was tested computationally, and using functional cell based assays.
      Computationally we demonstrate that conventional single cell sorting can sample
      as little as 50% of the population diversity dependant on the population
      distribution, and that Slice and Dice sorting samples much more of the variety
      present within a cell population. We then show by sorting single cells into wells
      using the Slice and Dice sorting method that there are cells sorted using this
      method that would be either rarely sorted, or not sorted at all using
      conventional single cell sorting approaches. The present study demonstrates a
      novel single cell sorting method that samples much more of the population
      diversity than current methods. It has implications in clonal selection, stem
      cell sorting, single cell sequencing and any areas where population heterogeneity
      is of importance.

PMID- 25944022
TI  - Trends in the treatment of early-stage Hodgkin lymphoma.

PMID- 25944024
TI  - Choroid plexus separation in fetuses without ventriculomegaly: Natural course and
      postnatal outcome.
AB  - PURPOSE: To evaluate fetuses with choroid plexus separation without
      ventriculomegaly in terms of fetal malformations, behavior of the separation
      during follow-up, and postnatal outcome. METHODS: In total, 172 fetuses with
      choroid plexus separation without ventriculomegaly were included in this
      prospective study. Fetal sonography was performed at 2- to 4-week intervals, and
      detailed physical and neurologic examinations were performed after their
      delivery. Fetuses were categorized into normal and abnormal subgroups according
      to the outcome. RESULTS: Sixteen fetuses (9.3%) were included in the abnormal
      outcome group and 156 fetuses (90.7%) were included in the normal-outcome group.
      Both the initial mean lateral ventricular diameter (9.3 mm versus 8.6 mm) and the
      initial mean choroid plexus separation (4.8 mm versus 3.3 mm) were greater in the
      abnormal group than in the normal group (p < 0.001 for both comparisons). We
      found that 4.0 mm was the best cutoff point of choroid plexus separation to
      detect a major anomaly, with 87.5% sensitivity and 93.6% specificity.
      CONCLUSIONS: Choroid plexus separation without ventriculomegaly often resolves
      within the third trimester and does not affect postnatal outcome. It can be
      associated with various fetal malformations; however, with a comprehensive
      examination, all fetal malformations can be detected prenatally. Follow-up
      sonography studies would be useful, especially in the case of suspected corpus
      callosum agenesis.

PMID- 25944023
TI  - The effect of a very brief smoking-reduction intervention in smokers who have no
      intention to quit: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Tobacco use is one of the most common preventable causes of death,
      but more than half of the Chinese men still use tobacco products. Moreover, 63.6%
      of Chinese smokers have stated that they would not consider quitting. Specialized
      and intensive smoking-cessation services are too expensive and passive to have
      major clinical and public health impacts in developing countries like China.
      Smoking cessation medications are not covered by medical insurance, and their
      high price prevents Chinese smokers from using them. Brief interventions are
      needed to provide cost-effective and timesaving tobacco dependence treatments in
      China mainland. METHODS/DESIGN: We describe a two-arm randomized controlled trial
      for smokers who have no intention to quit. The project will be conducted in
      outpatient clinics at a large hospital in Beijing, China. Both arms include one
      face-to-face interview plus five follow-up interventions. Each intervention will
      last approximately one minute. Subjects allocated to the smoking-reduction
      intervention arm (SRI) will be advised to reduce smoking consumption to at least
      half of their current consumption level within the next month. All subjects in
      the SRI will be warned to bear in mind that an attempt to reduce smoking is an
      intermediate step before complete cessation. Smokers who have successfully
      reduced their smoking consumption will be encouraged to completely cease smoking.
      Controls are subjects allocated to the exercise- and diet-advice arm (EDA) and
      will be given advice about healthy diet and physical activity, but the advice
      will not include smoking cessation or reduction. Data collection will be done at
      baseline and at each follow-up interview using standardized questionnaires. The
      primary outcomes include self-reported and biochemically verified 7-day point
      prevalence and prolonged abstinence rates at 12-month follow-up. DISCUSSION: We
      expect that an intention to quit in smoking outpatients can be motivated by
      physicians in the clinic setting. If this very brief smoking-reduction
      intervention can be demonstrated to have a positive impact on long-term smoking
      cessation, this strategy has the potential to be a viable and acceptable approach
      and may be used widely in China and elsewhere. CLINICAL TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT02370147 (date of registration: 23 th February, 2015).

PMID- 25944025
TI  - Nutritional Programming of Accelerated Puberty in Heifers: Involvement of Pro
      Opiomelanocortin Neurones in the Arcuate Nucleus.
AB  - The timing of puberty and subsequent fertility in female mammals are dependent on
      the integration of metabolic signals by the hypothalamus. Pro-opiomelanocortin
      (POMC) neurones in the arcuate nucleus (ARC) comprise a critical metabolic
      sensing pathway controlling the reproductive neuroendocrine axis. alpha
      Melanocyte-stimulating hormone (alphaMSH), a product of the POMC gene, has
      excitatory effects on gonadotrophin-releasing hormone (GnRH) neurones and fibres
      containing alphaMSH project to GnRH and kisspeptin neurones. Because kisspeptin
      is a potent stimulator of GnRH release, alphaMSH may also stimulate GnRH
      secretion indirectly via kisspeptin neurones. In the present work, we report
      studies conducted in young female cattle (heifers) aiming to determine whether
      increased nutrient intake during the juvenile period (4-8 months of age), a
      strategy previously shown to advance puberty, alters POMC and KISS1 mRNA
      expression, as well as alphaMSH close contacts on GnRH and kisspeptin neurones.
      In Experiment 1, POMC mRNA expression, detected by in situ hybridisation, was
      greater (P < 0.05) in the ARC in heifers that gained 1 kg/day of body weight
      (high-gain, HG; n = 6) compared to heifers that gained 0.5 kg/day (low-gain, LG;
      n = 5). The number of KISS1-expressing cells in the middle ARC was reduced (P <
      0.05) in HG compared to LG heifers. In Experiment 2, double-immunofluorescence
      showed limited alphaMSH-positive close contacts on GnRH neurones, and the
      magnitude of these inputs was not influenced by nutritional status. Conversely, a
      large number of kisspeptin-immunoreactive cells in the ARC were observed in close
      proximity to alphaMSH-containing varicosities. Furthermore, HG heifers (n = 5)
      exhibited a greater (P < 0.05) percentage of kisspeptin neurones in direct
      apposition to alphaMSH fibres and an increased (P < 0.05) number of alphaMSH
      close contacts per kisspeptin cell compared to LG heifers (n = 6). These results
      indicate that the POMC-kisspeptin pathway may be important in mediating the
      nutritional acceleration of puberty in heifers. 

PMID- 25944026
TI  - Alcohol and public health in Africa: can we prevent alcohol-related harm from
      increasing?
AB  - AIMS: According to the World Health Organization (WHO), the total amount of
      alcohol consumed in the African region is expected to increase due to the growth
      of new alcohol consumers, especially young people and women. With the changing
      alcohol environment, increases in the alcohol-attributable burden of disease are
      inevitable. To our knowledge, there has not been a comprehensive analysis of the
      factors that could be driving those increases. The objective of this study was to
      examine the evidence from peer reviewed literature regarding the factors that
      could be instrumental in this process, in order to inform strategic policy
      related decisions. METHOD: A narrative review was conducted using a thematic
      analysis approach. We searched papers published between January 2000 and July
      2014 in PubMed, the WHO's Global Health Library and African Journals Online.
      RESULTS: Our analysis identified seven factors (demographics, rapid urbanization,
      economic development, increased availability, corporate targeting, weak policy
      infrastructure and trade agreements) which are potentially tied to changes in
      alcohol consumption in Africa. Driven largely by globalization, a potential
      convergence of these various factors is likely to be associated with continued
      growth in alcohol consumption and alcohol-related morbidity and mortality.
      CONCLUSIONS: To address the emerging risk factors associated with increased
      alcohol consumption, African governments need to take a more active role in
      protecting the public's health. In particular, important strategic shifts are
      needed to increase implementation of intersectoral strategies, community
      involvement in the policy dialogue, health services re-orientation and better
      regulation of the alcohol beverage industry.

PMID- 25944027
TI  - Determination of phthalate esters from environmental water samples by micro-solid
      phase extraction using TiO2 nanotube arrays before high-performance liquid
      chromatography.
AB  - We describe a highly sensitive micro-solid-phase extraction method for the pre
      concentration of six phthalate esters utilizing a TiO2 nanotube array coupled to
      high-performance liquid chromatography with a variable-wavelength ultraviolet
      visible detector. The selected phthalate esters included dimethyl phthalate,
      diethyl phthalate, dibutyl phthalate, butyl benzyl phthalate, bis(2
      ethylhexyl)phthalate and dioctyl phthalate. The factors that would affect the
      enrichment, such as desorption solvent, sample pH, salting-out effect, extraction
      time and desorption time, were optimized. Under the optimum conditions, the
      linear range of the proposed method was 0.3-200 MUg/L. The limits of detection
      were 0.04-0.2 MUg/L (S/N = 3). The proposed method was successfully applied to
      the determination of six phthalate esters in water samples and satisfied spiked
      recoveries were achieved. These results indicated that the proposed method was
      appropriate for the determination of trace phthalate esters in environmental
      water samples. 

PMID- 25944028
TI  - Changing how we view aging.
AB  - It is time for medicine, particularly geriatric medicine, to incorporate an
      understanding of how the psychological aspects of aging interact with cancer. The
      impact has both negative elements--for example, the added stresses of other
      losses or comorbid ailments that come with age--and positive elements,
      particularly a lifetime of honing character strengths on which to draw during a
      challenging time.

PMID- 25944030
TI  - Erratum to: Widening Phenotypic Spectrum of AADC Deficiency, a Disorder of
      Dopamine and Serotonin Synthesis.

PMID- 25944029
TI  - Quality of life and physical function in adults treated with intensive
      chemotherapy for acute myeloid leukemia improve over time independent of age.
AB  - OBJECTIVES: Intensive chemotherapy (IC) is the primary treatment of acute myeloid
      leukemia (AML) but is associated with significant toxicity, particularly in older
      adults. We characterized the impact of AML and its treatment on quality of life
      (QOL) and physical function in younger (age 18-59) and older (age 60+) patients
      with AML over 1year from diagnosis. MATERIALS AND METHODS: AML patients
      undergoing IC without stem-cell transplant at two tertiary care centers were
      enrolled in a prospective, longitudinal study. Assessments were done pre-IC and
      at 7 time points over the next year. QOL, fatigue, and physical performance (grip
      strength, 2-minute walk test (2MWT), timed chair stands) were measured in all
      patients whereas daily function was measured only in older patients. Data were
      analyzed using mixed effects regression models. RESULTS: 237 patients were
      recruited (140 younger and 97 older, 56% male). One-year survival was 79% and 60%
      among younger and older patients, respectively. For patients in remission, global
      QOL and fatigue improved significantly over time (p<0.001 for both); trends were
      similar between older and younger patients. Grip strength did not change over
      time (p=0.58) whereas both the 2MWT (p<0.001) and timed chair stands (p<0.001)
      improved significantly. Daily function improved significantly over time
      (p=0.003). CONCLUSIONS: Survivors of AML in remission after IC achieve
      significant improvements in QOL, fatigue, and physical function over time with
      similar trajectories for older and younger patients. These data suggest that
      appropriately selected older patients do well following IC.

PMID- 25944031
TI  - An odor detection system based on automatically trained mice by relative go no-go
      olfactory operant conditioning.
AB  - Odor detection applications are needed by human societies in various
      circumstances. Rodent offers unique advantages in developing biologic odor
      detection systems. This report outlines a novel apparatus designed to train
      maximum 5 mice automatically to detect odors using a new olfactory, relative go
      no-go, operant conditioning paradigm. The new paradigm offers the chance to
      measure real-time reliability of individual animal's detection behavior with
      changing responses. All of 15 water-deprivation mice were able to learn to
      respond to unpredictable delivering of the target odor with higher touch
      frequencies via a touch sensor. The mice were continually trained with decreasing
      concentrations of the target odor (n-butanol), the average correct percent
      significantly dropped when training at 0.01% solution concentration; the alarm
      algorithm showed excellent recognition of odor detection behavior of qualified
      mice group through training. Then, the alarm algorithm was repeatedly tested
      against simulated scenario for 4 blocks. The mice acted comparable to the
      training period during the tests, and provided total of 58 warnings for the
      target odor out of 59 random deliveries and 0 false alarm. The results suggest
      this odor detection method is promising for further development in respect to
      various types of odor detection applications. 

PMID- 25944032
TI  - Evolution of chronic renal impairment and long-term mortality after de novo acute
      kidney injury in the critically ill; a Swedish multi-centre cohort study.
AB  - INTRODUCTION: Acute Kidney Injury (AKI) is common in critical ill populations and
      its association with high short-term mortality is well established. However, long
      term risks of death and renal dysfunction are poorly understood and few studies
      exclude patients with pre-existing renal disease, meaning outcome for de novo AKI
      has been difficult to elicit. We aimed to compare the long-term risk of Chronic
      Kidney Disease (CKD), End Stage Renal Disease (ESRD) and mortality in critically
      ill patients with and without severe de novo AKI. METHOD: This cohort study was
      conducted between 2005 and 2011 in Swedish intensive care units (ICU). Data from
      130134 adult patients listed on the Swedish intensive care register-database was
      linked with other national registries. Patients with pre-existing CKD (4192) and
      ESRD (1389) were excluded, as were cases (26771) with incomplete data. Patients
      were classified according to AKI exposure during ICU admission. Outcome in the de
      novo AKI group was compared to the non-exposed (no-AKI) intensive care control
      group. Primary outcome was all-cause mortality. Follow-up ranged from one to
      seven years (median 2.1 years). Secondary outcomes were incidence of CKD and ESRD
      and median follow-up was 1.3 years. RESULTS: Of 97 782 patients, 5273 (5.4%) had
      de novo AKI. These patients had significantly higher crude mortality at one
      (48.4% vs. 24.6%) and five years (61.8% vs. 39.1%) compared to the control group.
      The first 30% of deaths in AKI patients occurred within 11 days of ICU admission
      whilst the 30-centile in the no-AKI group died by 748 days. CKD was significantly
      more common in AKI survivors at one year (6.0% vs. 0.44%) than in no-AKI group
      (adjusted incidence rate ratio (IRR) 7.6). AKI patients also had significantly
      higher rates of ESRD at one (2.0% vs. 0.08%) and at five years (3.9% vs. 0.3%)
      than those in the comparison group (adjusted IRR 22.5). CONCLUSION: This large
      cohort study demonstrated that de novo AKI is associated with increased short and
      long-term risk of death. AKI is independently associated with increased risk of
      CKD and ESRD as compared to an ICU control population. Severe de novo AKI
      survivors should be routinely followed-up and their renal function monitored.

PMID- 25944034
TI  - Words of Wisdom. Re: incidence of prostate cancer in hypogonadal men receiving
      testosterone therapy: observations from 5-year median followup of 3 registries.

PMID- 25944033
TI  - Lobular carcinoma in situ (LCIS) of the breast: is long-term outcome similar to
      ductal carcinoma in situ (DCIS)? Analysis of 200 cases.
AB  - BACKGROUND: Lobular carcinomas in situ (LCIS) represent 1-2% of all breast
      cancers. Both significance and treatment remain widely debated, as well as the
      possible similarities with DCIS. MATERIALS AND METHODS: Two hundred patients with
      pure LCIS were retrospectively analyzed in seven centres from 1990 to 2008.
      Median age was 52 years; 176 patients underwent breast-conserving surgery (BCS)
      and 24 mastectomy. Seventeen patients received whole breast irradiation (WBRT)
      after BCS and 20 hormonal treatment (15 by tamoxifen). RESULTS: With a 144-month
      median follow-up (FU), there were no local recurrences (LR) among 24 patients
      treated by mastectomy. With the same FU, 3 late LR out of 17 (17%) occurred in
      patients treated by BCS and WBRT (with no LR at 10 years). Among 159 patients
      treated by BCS alone, 20 developed LR (13%), but with only a 72-month FU (17.5%
      at 10 years). No specific LR risk factors were identified. Three patients
      developed metastases, two after invasive LR; 22 patients (11%) developed
      contralateral BC (59% invasive) and another five had second cancer. CONCLUSIONS:
      LCIS is not always an indolent disease. The long-term outcome is quite similar to
      most ductal carcinomas in situ (DCIS). The main problems are the accuracy of
      pathological definition and a clear identification of more aggressive subtypes,
      in order to avoid further invasive LR. BCS + WBRT should be discussed in some
      selected cases, and the long-term results seem comparable to DCIS.

PMID- 25944035
TI  - Words of Wisdom. Re: Multiparametric Magnetic Resonance Imaging (MRI) and
      Subsequent MRI/Ultrasonography Fusion-guided Biopsy Increase the Detection of
      Anteriorly Located Prostate Cancers.

PMID- 25944036
TI  - Words of Wisdom. Re: Perceptions of Active Surveillance and Treatment
      Recommendations for Low-risk Prostate Cancer: Results from a National Survey of
      Radiation Oncologists and Urologists.

PMID- 25944037
TI  - Words of Wisdom. Re: Combination Treatment with Mirabegron and Solifenacin in
      Patients with Overactive Bladder: Efficacy and Safety Results from a Randomised,
      Double-blind, Dose-ranging, Phase 2 Study (Symphony).

PMID- 25944038
TI  - Words of Wisdom. Re: outcome of transvaginal mesh and tape removed for pain only.

PMID- 25944039
TI  - Words of Wisdom. Re: robotic intracorporeal orthotopic neobladder during radical
      cystectomy in 132 patients.

PMID- 25944040
TI  - Rolf Ackermann (1941-2015): European urologist and gentleman.

PMID- 25944041
TI  - Corrigendum to "Targeted Prostate Cancer Screening in BRCA1 and BRCA2 Mutation
      Carriers: Results from the Initial Screening Round of the IMPACT Study" [Eur Urol
      2014;66:489-99].

PMID- 25944043
TI  - Palladium-catalysed oxidative cross-esterification between two alcohols.
AB  - A simple palladium-catalysed oxidative cross-coupling between two different
      alcohols was developed. Various benzylic alcohols could couple with aliphatic
      alcohols in excellent yields. The use of benzyl chloride as the oxidant and the
      amount of aliphatic alcohol were both important for achieving the reaction
      selectivity. 

PMID- 25944044
TI  - Determining structural ensembles of flexible multi-domain proteins using small
      angle X-ray scattering and molecular dynamics simulations.

PMID- 25944048
TI  - Advanced anatomical and functional imaging guides management of coronary artery
      ulcerated plaque.

PMID- 25944046
TI  - Expression of heterologous sigma factors enables functional screening of
      metagenomic and heterologous genomic libraries.
AB  - A key limitation in using heterologous genomic or metagenomic libraries in
      functional genomics and genome engineering is the low expression of heterologous
      genes in screening hosts, such as Escherichia coli. To overcome this limitation,
      here we generate E. coli strains capable of recognizing heterologous promoters by
      expressing heterologous sigma factors. Among seven sigma factors tested, RpoD
      from Lactobacillus plantarum (Lpl) appears to be able of initiating transcription
      from all sources of DNA. Using the promoter GFP-trap concept, we successfully
      screen several heterologous and metagenomic DNA libraries, thus enlarging the
      genomic space that can be functionally sampled in E. coli. For an application, we
      show that screening fosmid-based Lpl genomic libraries in an E. coli strain with
      a chromosomally integrated Lpl rpoD enables the identification of Lpl genetic
      determinants imparting strong ethanol tolerance in E. coli. Transcriptome
      analysis confirms increased expression of heterologous genes in the engineered
      strain. 

PMID- 25944047
TI  - Assessment of acute changes in ventricular volumes, function, and strain after
      interventional edge-to-edge repair of mitral regurgitation using cardiac magnetic
      resonance imaging.
AB  - AIMS: Whereas haemodynamic and echocardiographic studies suggest benefits for
      left ventricular (LV) function and cardiac output following reduction in LV
      preload by interventional edge-to-edge repair for mitral regurgitation (MR),
      there is limited data on volumetric and functional LV and right ventricular (RV)
      changes using cardiac magnetic resonance (CMR) imaging. METHODS AND RESULTS:
      Patients with moderate to severe MR and high surgical risk underwent MitraClip
      implantation and CMR imaging before and within 7 days after the procedure. In
      addition to volumetric and flow studies, myocardial feature tracking (FT)
      technology for quantification of myocardial strain was applied. Twenty patients
      (age: 76 +/- 8 years) with functional (n = 15) or degenerative MR (n = 5) with a
      mean logistic Euroscore I of 33 +/- 16 underwent both successful MitraClip
      implantation and CMR imaging. MR fraction (36 +/- 10 vs. 19 +/- 12%; P < 0.001)
      and LV end-diastolic volume (115 +/- 36 vs. 105 +/- 41 mL/m2; P = 0.002)
      decreased significantly, whereas LV ejection fraction (42 +/- 15 vs. 41 +/- 16%,
      P = 0.8) and cardiac index (1.7 +/- 0.5 vs. 1.8 +/- 0.4 L/min/m2, P = 0.4)
      remained unchanged. MitraClip implantation resulted in a significant impairment
      of circumferential (-12.8 +/- 4.8 vs. -8.2 +/- 3.3; P = 0.002) and radial strain
      (15.4 +/- 7.7 vs. 9.6 +/- 5.3; P = 0.02) on basal short-axis view. On RV level,
      there were no significant changes in end-diastolic volume (83 +/- 19 vs. 84 +/-
      18 mL/m2, P = 0.8), ejection fraction (42 +/- 9 vs. 43 +/- 11%, P = 0.8), or
      tricuspid regurgitation fraction (24 +/- 17 vs. 25 +/- 19%, P = 0.7). MitraClip
      implantation led to a significant improvement in New York Heart Association
      functional class (patients in functional class III-IV pre 100% vs. post 45%; P <
      0.001). CONCLUSION: In severely compromised patients, marked reduction in MR by
      MitraClip implantation might not result in immediate improved cardiac output and
      effective biventricular forward flow.

PMID- 25944049
TI  - Correlation between left atrial appendage morphology and flow velocity in
      patients with paroxysmal atrial fibrillation.
AB  - AIMS: Reduction of left atrial appendage (LAA) flow velocity (FV) is a risk
      factor for thrombus formation and increases the risk of stroke in patients with
      atrial fibrillation (AF). Furthermore, LAA morphology is correlated with stroke
      in patients with AF. The aim of this study was to correlate LAAFV with LAA
      morphology in patients with AF. METHODS AND RESULTS: We studied 96 patients (age
      59.0 +/- 10.2 years, 75% male) referred for radiofrequency catheter ablation for
      paroxysmal AF. All patients underwent computed tomography (CT) and transthoracic
      and transoesophageal echocardiography during sinus rhythm. LAA morphology was
      classified as one of the four types (chicken wing, windsock, cactus, and
      cauliflower) on CT images. There were significant differences in LAAFV among LAA
      morphologies (chicken wing 73.7 +/- 21.9 cm/s, windsock 61.9 +/- 19.6 cm/s,
      cactus 55.3 +/- 14.1 cm/s, cauliflower 52.7 +/- 18.1 cm/s, P = 0.008). Post hoc
      multiple comparisons showed that LAAFV was higher in patients with chicken wing
      than in those with cactus (P = 0.006, vs. chicken wing) and cauliflower (P =
      0.006, vs. chicken wing), but not with windsock (P = 0.102). After adjustment for
      clinical and LAA anatomical covariates (orifice area, volume, and trabeculation),
      multiple linear regression analyses revealed that LAA morphology was an
      independent determinant of LAAFV [chickens wing: standardized partial regression
      coefficients (beta) = 0.317, P = 0.0014; windsock: beta = 0.303, P = 0.038].
      CONCLUSION: LAA morphology is a significant determinant of LAAFV, suggesting an
      underlying mechanism for the association between LAA morphology and embolic
      events.

PMID- 25944045
TI  - Intranasal and oral vaccination with protein-based antigens: advantages,
      challenges and formulation strategies.
AB  - Most pathogens initiate their infections at the human mucosal surface. Therefore,
      mucosal vaccination, especially through oral or intranasal administration routes,
      is highly desired for infectious diseases. Meanwhile, protein-based antigens
      provide a safer alternative to the whole pathogen or DNA based ones in vaccine
      development. However, the unique biopharmaceutical hurdles that intranasally or
      orally delivered protein vaccines need to overcome before they reach the sites of
      targeting, the relatively low immunogenicity, as well as the low stability of the
      protein antigens, require thoughtful and fine-tuned mucosal vaccine formulations,
      including the selection of immunostimulants, the identification of the suitable
      vaccine delivery system, and the determination of the exact composition and
      manufacturing conditions. This review aims to provide an up-to-date survey of the
      protein antigen-based vaccine formulation development, including the usage of
      immunostimulants and the optimization of vaccine delivery systems for intranasal
      and oral administrations. 

PMID- 25944050
TI  - Cardiovascular imaging practice in Europe: a report from the European Association
      of Cardiovascular Imaging.
AB  - The need for cardiovascular imaging (CVI) is expected to increase over the coming
      years due to the changes in CV disease epidemiology and ageing of the population.
      However, reliable statistics on CVI practice in Europe are lacking. Establishing
      the current status of the use of CVI across Europe has become the first
      comprehensive project of the European Association of Cardiovascular Imaging and
      the European Society of Cardiology Taskforce on CVI. In 2013, a survey with
      relevant information regarding CVI was sent to all National
      Imaging/Echocardiography Societies and Working Groups. Representatives from 41
      countries returned the questionnaire. The present report provides key results of
      the survey, relating to existing education, training, certification and national
      accreditation programmes, healthcare organizations, and reimbursement systems. 

PMID- 25944051
TI  - Quantitative myocardial perfusion by O-15-water PET: individualized vs.
      standardized vascular territories.
AB  - AIMS: Reporting of quantitative myocardial blood flow (MBF) is typically
      performed in standard coronary territories. However, coronary anatomy and
      myocardial vascular territories vary among individuals, and a coronary artery may
      erroneously be deemed stenosed or not if territorial demarcation is incorrect. So
      far, the diagnostic consequences of calculating individually vs. standardly
      assessed MBF values have not been reported. We examined whether individual
      reassignment of vascular territories would improve the diagnostic accuracy of MBF
      with regard to the detection of significant coronary artery disease (CAD).
      METHODS AND RESULTS: Forty-four patients with suspected CAD were included
      prospectively and underwent coronary CT-angiography and quantitative MBF
      assessment with O-15-water PET followed by invasive, quantitative coronary
      angiography, which served as reference. MBF was calculated in the vascular
      territories during adenosine stress according to a standardized 17-segment
      American Heart Association model and an individualized model, using CT
      angiography to adjust the coronary territories to their feeding vessels.
      Individually defined territories deviated from standard territories in 52% of
      patients. However, MBF in the three coronary territories defined by standard and
      individualized models did not differ significantly, except in one patient, in
      whom the MBF of an individualized coronary territory deviated sufficiently as to
      change the test from a false positive to a true negative result in this
      particular territory. CONCLUSION: Disparity between standardized and
      individualized vascular territories was present in half of the patients, but had
      little clinical impact. Still, caution should be taken not always to rely on
      standard territories, as this may at times cause misinterpretation.

PMID- 25944052
TI  - Laser-pointer-induced self-focusing effect in hybrid-aligned dye-doped liquid
      crystals.
AB  - Nonlinear optics deals with phenomena where "light controls light"; e.g., there
      is mediation by an intensity-dependent medium through which light propagates.
      This field has attracted much attention for its immense potential in applications
      dependent on nonlinear processes, such as frequency conversion, multiple-photon
      absorption, self-phase modulation, and so on. However, such nonlinearities are
      typically only observed at very high light intensities and thus they require
      costly lasers. Here, we report on a self-focusing effect induced with a 1 mW
      handheld laser pointer. We prepared polymer-stabilized dye-doped liquid crystals,
      in which the molecular director orientation gradually changes from homeotropic at
      one surface to homogeneous at the other. This is referred to as hybrid alignment.
      In such films, the threshold intensity needed to form diffraction rings was
      reduced by a factor of 8.5 compared to that in conventional homeotropic cells,
      which enabled the induction of the self-focusing effect with a laser pointer. 

PMID- 25944053
TI  - MicroRNA-155 modulates P2R signaling and Th2 priming of dendritic cells during
      allergic airway inflammation in mice.
AB  - BACKGROUND: Dendritic cells (DCs) are the professional antigen-presenting cells
      (APCs) in the lung. They are known to be key players in the induction and
      maintenance of allergic asthma by cross-linking innate and adaptive immune
      responses. MicroRNAs (miRNAs) are known to influence cell fate and function by
      translational suppression or induction of messenger RNA (mRNA) degradation. miR
      155 has been shown to be a crucial regulator of the immune system. However, its
      function in the pathogenesis of allergic airway inflammation (AAI) is not
      completely elucidated yet. METHODS: Wild type (WT) and miR-155-deficient (miR
      155(-/-) ) mice were used in ovalbumin (OVA) and house dust mite (HDM) models of
      AAI. Adoptive transfer of sensitized DCs to the lungs, migration, and T-cell
      priming assays were used to investigate the functional relevance of miR-155 in
      DCs. RESULTS: miR-155(-/-) mice showed reduced eosinophilic airway inflammation
      compared to WT mice in both models of AAI. Furthermore, miR-155(-/-) DCs showed
      limited Th2 priming capacity and failed to induce airway inflammation in allergen
      exposed WT mice. miR-155 deficiency on DCs was also associated with impaired
      purinergic receptor signaling, as miR-155(-/-) DCs showed reduced chemotaxis and
      IL-1beta secretion upon stimulation with ATP, probably due to direct targeting of
      ectonucleoside triphosphate diphosphohydrolases (ENTPD) by miR-155. CONCLUSIONS:
      miR-155 deficiency alleviates AAI by diminishing Th2 priming capacity and ATP
      /P2R-induced activation of DCs in mice, suggesting this miRNA as a potential
      therapeutic target of AAI.

PMID- 25944054
TI  - Targeting molecular interactions essential for Plasmodium sexual reproduction.
AB  - Malaria remains one of the most devastating infectious diseases, killing up to a
      million people every year. Whereas much progress has been made in understanding
      the life cycle of the parasite in the human host and in the mosquito vector,
      significant gaps of knowledge remain. Fertilization of malaria parasites, a
      process that takes place in the lumen of the mosquito midgut, is poorly
      understood and the molecular interactions (receptor-ligand) required for
      Plasmodium fertilization remain elusive. By use of a phage display library, we
      identified FG1 (Female Gamete peptide 1), a peptide that binds specifically to
      the surface of female Plasmodium berghei gametes. Importantly, FG1 but not a
      scrambled version of the peptide, strongly reduces P. berghei oocyst formation by
      interfering with fertilization. In addition, FG1 also inhibits P. falciparum
      oocyst formation suggesting that the peptide binds to a molecule on the surface
      of the female gamete whose structure is conserved. Identification of the
      molecular interactions disrupted by the FG1 peptide may lead to the development
      of novel malaria transmission-blocking strategies. 

PMID- 25944055
TI  - The Formation of CO by Thermal Decomposition of Formic Acid under Electrochemical
      Conditions of CO2 Reduction.
AB  - We report that the thermal decomposition of formic acid to CO may occur under
      electrochemically-relevant conditions by mild heating. These thermal effects may
      play a role in the outcome of electrolytic experiments as an artifact of
      resistive, local heating and illumination. This non-Faradaic reactivity pathway
      may therefore need consideration in the analysis of electrochemical data on CO2
      reduction to formic acid and CO and may become a hindrance in scaleup efforts of
      these chemical transformations. IR visual thermometry provides evidence of
      macroscopic heating effects during electrolytic experiments. 

PMID- 25944056
TI  - Ctbp2 Modulates NuRD-Mediated Deacetylation of H3K27 and Facilitates PRC2
      Mediated H3K27me3 in Active Embryonic Stem Cell Genes During Exit from
      Pluripotency.
AB  - For cells to exit from pluripotency and commit to a lineage, the circuitry of a
      core transcription factor (CTF) network must be extinguished in an orderly manner
      through epigenetic modifications. However, how this choreographed epigenetic
      remodeling at active embryonic stem cell (ESC) genes occurs during
      differentiation is poorly understood. In this study, we demonstrate that C
      terminal binding protein 2 (Ctbp2) regulates nucleosome remodeling and
      deacetylation (NuRD)-mediated deacetylation of H3K27 and facilitates recruitment
      of polycomb repressive complex 2 (PRC2)-mediated H3K27me3 in active ESC genes for
      exit from pluripotency during differentiation. By genomewide analysis, we found
      that Ctbp2 resides in active ESC genes and co-occupies regions with ESC CTFs in
      undifferentiated ESCs. Furthermore, ablation of Ctbp2 effects inappropriate gene
      silencing in ESCs by sustaining high levels of H3K27ac and impeding H3K27me3 in
      active ESC genes, thereby sustaining ESC maintenance during differentiation.
      Thus, Ctbp2 preoccupies regions in active genes with the NuRD complex in
      undifferentiated ESCs that are directed toward H3K27me3 by PRC2 to induce stable
      silencing, which is pivotal for natural lineage commitment.

PMID- 25944058
TI  - A one-season prospective study of injuries and illness in elite junior tennis.
AB  - The objective of this study was to estimate the incidence and prevalence of
      injury and illness among elite junior tennis players. A cohort of 73 players (11
      14 years) in the 2012-2013 Dutch national high-performance program was followed
      for 32 weeks; all participants completed the study. The OSTRC Questionnaire on
      Health Problems was used to record self-reported injuries and illnesses and to
      record training and match exposure. Main outcome measures were average prevalence
      of overuse injury and illness and incidence density of acute injury. On average,
      players practiced 9.1 h/week (SD 0.6; range 2.3-12.0) and had 2.2 h of match play
      (SD 0.6; range 2.3-12.0). During the course of the study, 67 players reported a
      total of 187 health problems. The average weekly prevalence of all health
      problems was 21.3% (95% CI: 19.2-22.9), of which 12.1% (95% CI: 10.9-13.3)
      constituted overuse injuries and 5.8% (95% CI: 4.6-6.9) illnesses. The incidence
      of acute injuries was 1.2/1000 h of tennis play (95% CI: 0.7-1.7). The high
      occurrence of overuse injuries among elite junior tennis players suggests that an
      early focus on preventative measures is warranted, with a particular focus on the
      monitoring and management of workload. 

PMID- 25944057
TI  - Decoding the oak genome: public release of sequence data, assembly, annotation
      and publication strategies.
AB  - The 1.5 Gbp/2C genome of pedunculate oak (Quercus robur) has been sequenced. A
      strategy was established for dealing with the challenges imposed by the
      sequencing of such a large, complex and highly heterozygous genome by a whole
      genome shotgun (WGS) approach, without the use of costly and time-consuming
      methods, such as fosmid or BAC clone-based hierarchical sequencing methods. The
      sequencing strategy combined short and long reads. Over 49 million reads provided
      by Roche 454 GS-FLX technology were assembled into contigs and combined with
      shorter Illumina sequence reads from paired-end and mate-pair libraries of
      different insert sizes, to build scaffolds. Errors were corrected and gaps filled
      with Illumina paired-end reads and contaminants detected, resulting in a total of
      17,910 scaffolds (>2 kb) corresponding to 1.34 Gb. Fifty per cent of the assembly
      was accounted for by 1468 scaffolds (N50 of 260 kb). Initial comparison with the
      phylogenetically related Prunus persica gene model indicated that genes for 84.6%
      of the proteins present in peach (mean protein coverage of 90.5%) were present in
      our assembly. The second and third steps in this project are genome annotation
      and the assignment of scaffolds to the oak genetic linkage map. In accordance
      with the Bermuda and Fort Lauderdale agreements and the more recent Toronto
      Statement, the oak genome data have been released into public sequence
      repositories in advance of publication. In this presubmission paper, the oak
      genome consortium describes its principal lines of work and future directions for
      analyses of the nature, function and evolution of the oak genome.

PMID- 25944059
TI  - Mini nutritional assessment test long and short form are valid screening tools in
      Turkish older adults.
AB  - BACKGROUND: Malnutrition is a pitfall in older adults despite its high prevalence
      and serious consequences. There are various screening tests however, none of them
      have been validated for our country. In this study, we aimed to test the
      hypothesis that MNA (long form of MNA) and MNA-SF (short form of MNA) are
      applicable to screen malnutrition in Turkish geriatric patients. MATERIALS AND
      METHODS: Two hundred and thirty-six patients aged 65 years and over who were
      admitted to our geriatric medicine outpatient clinic were enrolled in the study.
      Four groups of data (anthropometric measurements, biochemical markers, three-day
      diet record and geriatric assessment scales) were recorded. Long and short forms
      of MNA test were performed. Two different geriatricians interpreted the patients'
      nutritional status with the aid of aforementioned data. Patients were divided
      into three groups which were patients with malnutrition, with malnutrition risk
      and well-nourished. Concordance between the two geriatricians' clinical
      assessment was analyzed by kappa statistics. Excellent concordance was found,
      therefore the first specialist's decisions were accepted as gold-standard. A
      third physician performed the long and short forms of MNA test. The concordance
      between the first clinician's assessment and MNA test results were compared
      subsequently. RESULTS: MNA and MNA-SF results were compared with first
      clinician's decision of malnutrition and kappa coefficients were 0.68 and 0.66,
      respectively. Sensitivity analysis indicated that MNA was 92% sensitive and 86%
      specific, whereas MNA-SF was 94% sensitive and 81% specific. CONCLUSION: MNA and
      MNA-SF are suitable for malnutrition screening in Turkish older adults.

PMID- 25944060
TI  - Cardiovascular disease (CVD) risk factors in older adults - Perception and
      reality.
AB  - OBJECTIVE: CVD are the leading causes of death and disability in the world. Since
      there are no published data about the knowledge of CVD risk factors among
      Croatian older adults, this was the primary aim of this study. Another aim was to
      determine relationship between actual CVD risk (total cholesterol - TC and
      triglyceride levels - TG, blood pressure - BP, body mass index - BMI, smoking)
      and self-assessed CVD risk among older adults. METHODS: We used a cross-sectional
      epidemiological study in which participants (969 subjects aged >70 years)
      answered a written questionnaire. Participants' BMI, BP, TC and triglycerides
      were measured. RESULTS: The actual presence of CVD risk factors in participants
      did not appear to alter their perceptions of risk compared to participants
      without CVD risk factors (the percentage of participants who think that they have
      moderate/high CVD risk is almost the same: 75.5% among participants with actual
      CVD risk factors; 75.7% among those without CVD risk factors). Accordingly, 24.5%
      of participants with actual CVD risk factors failed to recognize that risk. Only
      23.4% of participants correctly recognized BP target values, while 49.8%
      participants successfully recognized TC target levels. The knowledge of target BP
      and/or TC levels did not influence participants' ability to assess their own CVD
      risk. Surprisingly, 41.8% of participants reported that they have not discussed
      CVD risk factors with their physicians. CONCLUSION: The results suggest
      insufficient awareness of CVD risk factors among Croatian older adults and a need
      for improved promotion of CVD prevention in this population segment.

PMID- 25944061
TI  - Private practice is unethical-and doctors should give it up.

PMID- 25944062
TI  - RhoA/ROCK1 regulates Avian Reovirus S1133-induced switch from autophagy to
      apoptosis.
AB  - BACKGROUND: Autophagy is an essential process in the control of cellular
      homeostasis. It enables cells under certain stress conditions to survive by
      removing toxic cellular components, and may protect cells from apoptosis. In the
      present study, the signaling pathways involved in ARV S1133 regulated switch from
      autophagy to apoptosis were investigated. RESULTS: ARV S1133 infection caused
      autophagy in the early to middle infectious stages in Vero and DF1 cells, and
      apoptosis in the middle to late stages. Conversion of the autophagy marker LC3-I
      to LC3-II occurred earlier than cleavage of the apoptotic marker caspase-3. ARV
      S1133 also activated the Beclin-1 promoter in the early to middle stages of
      infection. Levels of RhoA-GTP and ROCK1 activity were elevated upon ARV S1133
      infection, while inhibition of RhoA and ROCK1 reduced autophagy and subsequent
      apoptosis. Conversely, inhibition of caspase-3 did not affect the level of
      autophagy. Beclin-1 knockdown and treatment with autophagy inhibitors, 3-MA and
      Bafilomycin A1, suppressed ARV S1133-induced autophagy and apoptosis
      simultaneously, suggesting the shift from autophagy to apoptosis. A co
      immunoprecipitation assay demonstrated that the formation of a RhoA, ROCK1 and
      Beclin-1 complex coincided with the induction of autophagy. CONCLUSION: Our
      results demonstrate that RhoA/ROCK1 signaling play critical roles in the
      transition of cell activity from autophagy to apoptosis in ARV S1133-infected
      cells.

PMID- 25944064
TI  - Use Of External Intrathecal Infusion Pumps In The Management Of Septic
      Complications: A Case Report.
AB  - Spasticity is a motor disorder with an increased muscle tone, typically
      associated with spasms, weakness and lack of coordination. It is an invalidating
      and debilitating pathology, characterized by pain, limited autonomy in activities
      of daily living, development of severe lesions. Spasticity can be adequately
      treated with physiotherapy, muscle relaxants drugs or topical treatment with
      botulinic toxin type A. Intrathecal baclofen therapy is very effective in the
      treatment of severe and generalized spasticity. Sometimes, soft tissues adjacent
      to the implant intrathecal infusion become infected; removing intrathecal
      infusion and systemic antibiotic therapy are best solution for clinical cure.
      However, removing intrathecal baclofen therapy could increase muscle spasticity
      with enhancement of pain and clonus that can worsen quality of life. In this
      study, we evaluated clinical improvement after complete healing of the septic
      focus and implantation of a new infuser. 

PMID- 25944063
TI  - Higher Waist Circumference, Fasting Hyperinsulinemia And Insulin Resistance
      Characterize Hypertensive Patients With Impaired Glucose Metabolism.
AB  - Hypertensive patients are at higher risk of pre-diabetes (impaired fasting
      glucose IFG and impaired glucose tolerance IGT) and type 2 DM. This study was
      done to examine whether some general, anthropometric, hormone, and metabolic
      parameters are different between subjects with normal and impaired glucose
      metabolism (IGM) in hypertensive subjects, thus possibly identifying some
      variable characterizing glucose metabolism derangement in these patients. A
      cohort of 134 hypertensive patients, 55 women and 79 men, aged 37-70 years, were
      examined. IGM patients were considered those showing IFG and/or IGT or type 2 DM
      after an oral glucose tolerance test (OGTT), and/or HbA1c > 48 mmol/l (6.5%)
      and/or glucose levels >155 mg/dL after 1 hour of the OGTT. Body mass index (BMI),
      waist circumference, and fasting insulin, TSH, FT3, FT4, glucose, and lipid
      (cholesterol, HDL-cholesterol and triglycerides) plasma concentrations were
      measured. Insulin resistance was also assessed by the homeostasis model
      assessment (HOMAIR). RESULTS: Waist circumference (p < 0.05), fasting glucose (p
      < 0.05) and insulin levels (p < 0.05) and HOMAIR (p < 0.05) were significantly
      higher in patients with IGM than in control group. All other investigated
      parameters, as well as the number of antihypertensive drugs per single patient,
      were not different between the two groups. CONCLUSIONS: The present study,
      performed in a selected population of hypertensive subjects, shows that
      derangement of glucose metabolism is associated to central fat accumulation,
      hyperinsulinemia and insulin resistance.

PMID- 25944065
TI  - Disseminated lymphoma with large granular lymphocyte morphology diagnosed in a
      horse via abdominal fluid and transtracheal wash cytology.
AB  - A 22-year-old Tennessee Walking Horse mare was presented to the Auburn University
      Large Animal Teaching Hospital with a 3-day history of lethargy, anorexia, and
      mild signs of colic. The mare had a several-month history of weight loss and
      refractory cough. Physical examination revealed an increased respiratory rate,
      and crackles and wheezes were heard on thoracic auscultation. Thoracic
      ultrasonographic examination showed disseminated, minor, bilateral comet tail
      like lesions on the parietal pleural surfaces. Abdominal ultrasonographic
      examination was unremarkable. Trans-rectal palpation revealed a firm small colon
      impaction with concomitant diarrhea. Laboratory data were characterized by a very
      pronounced acute inflammatory leukogram with severe neutropenia and significant
      left shift, evidence of hepatocellular damage/necrosis, cholestasis, and possibly
      mixed metabolic alkalosis and acidosis. On cytologic evaluation of a peritoneal
      fluid sample, there were many large granular lymphocytes (LGL). Large numbers of
      LGL were also observed on cytologic examination of a subsequent transtracheal
      wash. The final cytologic interpretation was disseminated lymphoma with LGL
      morphology. Due to worsening of the clinical signs and poor prognosis, the mare
      was euthanized. On necropsy and in histopathologic examination, disseminated
      lymphoma with LGL morphology was noted in a mesenteric lymph node, lungs, liver,
      spleen, kidneys, and right dorsal colon. Lymphoma with LGL morphology is rarely
      diagnosed in the horse. This report provides unique cytologic findings of a case
      of disseminated lymphoma with LGL morphology in a horse, confirmed with
      histopathologic evaluation. 

PMID- 25944066
TI  - [Multiple endocrine neoplasia type 2B].
AB  - BACKGROUND: Multiple endocrine neoplasia type 2b (MEN2B) is a rare syndrome
      characterised by the occurrence of medullary thyroid carcinoma at a young age in
      all patients, and phaeochromocytoma at a later age in half of the patients. Once
      a medullary thyroid carcinoma causes symptoms, it has usually already
      metastasised to the lymph nodes and curative treatment is seldom possible at that
      stage. CASE DESCRIPTION: We present two patients who had phenotypical
      characteristics of the MEN2B syndrome from a young age: mucosal neuromas, ptosis,
      a marfanoid habitus, gastrointestinal problems and crying without tears. When the
      diagnosis was made, at the ages of 15 and 10 years respectively, both patients
      had already developed metastatic medullary thyroid carcinoma. CONCLUSION: Early
      recognition of the phenotype of MEN2B syndrome is crucial in order to be able to
      perform a prophylactic or curative thyroidectomy. The mucosal neuromas, which are
      usually present from infancy, are a particularly important characteristic.

PMID- 25944067
TI  - [Kernicterus is preventable but still occurs].
AB  - Kernicterus is a severe neurological condition, caused by bilirubin-induced
      damage in the basal ganglia. The neurological outcome is often poor. In the past
      decades there seems to have been an increase in the number of reported cases of
      kernicterus. In order to raise awareness of this condition, we present two
      patients with kernicterus caused by different pathophysiological mechanisms. In
      both cases we make suggestions for the improvement of the medical care process.
      The first patient is a 7-day-old girl with kernicterus due to haemolysis caused
      by G6PD deficiency. Patient B is a 3-day-old boy with hyperbilirubinaemia based
      on 0/B blood group incompatibility. Kernicterus resulted in significant
      disabilities in these children. A proper diagnostic approach and precise
      treatment of hyperbilirubinaemia are essential to prevent major neurological
      damage. Awareness of this condition, education of health care professionals and
      changes in in- and outpatient care are needed to achieve this goal. 

PMID- 25944068
TI  - [Value of a multidisciplinary team for patients with a urological malignancy].
AB  - OBJECTIVE: To evaluate degree of agreement between treatment proposals from
      urologist and a multidisciplinary team (MDT) for patients with an urological
      malignancy. DESIGN: Retrospective cohort study. METHOD: All letters from patients
      with an urological malignancy of prostate, bladder, kidney or testicle who were
      discussed at the MDT in Ziekenhuisgroep Twente from January 2011 until January
      2013 were collected. This study studied the level and frequency of agreement
      between treatment proposals from urologist and MDT. Level of agreement was
      expressed by using Cohen's Kappa. Also treatments proposed by the MDT were
      compared to the final treatment choice of the patient. RESULTS: A total of 788
      letters were analysed. For 9%, the MDT disagreed with the treatment recommended
      by the urologist. This disagreement was most often observed in patients with
      malignancy of kidney (kappa: 0.507; p < 0.001). Agreement for patients with
      malignancy of bladder, testicle and prostate were substantial (respectively
      kappa: 0.719; p < 0.001, kappa: 0.803; p < 0.001, kappa: 0.634; p < 0.001).
      Treatment proposals "brachytherapy" and "external radiotherapy" for prostate
      malignancy showed only moderate agreement (kappa: 0.564 and kappa: 0.568; p <
      0.001 respectively). 93% of all patients elected to take (one of) the treatment
      proposals made by the MDT. CONCLUSION: A multidisciplinary approach seems
      particularly useful for patients with malignancy of kidney. The additative value
      of MDT was less visible for patients with malignancy of prostate, which could be
      due to less consistent guidelines. Final treatment decision might be influenced
      by explanation and guidance of the treating urologist.

PMID- 25944070
TI  - [A man with a dislocated hip].
AB  - A 95-year-old male presented with a dislocated hip hemiarthroplasty after falling
      off his chair. After closed reposition, symptoms of dislocation remained. A
      control X-ray showed a disassociation of the prosthesis at the head-neck
      interface. Therefore, open reposition was performed. X-ray control is important
      to encounter complications, which can occur after reposition. 

PMID- 25944069
TI  - [A baby with digoxin toxicity].
AB  - Accidental poisoning or overdoses occur frequently in children. These are
      difficult to recognise because young children cannot communicate their symptoms;
      this means that specific symptoms can be missed, which can delay the diagnosis. A
      5-month-old boy was accidently given a tenfold dose of digoxin for 5 days. He
      developed feeding difficulties, vomiting, weight loss, elevated urea and
      creatinine levels, hyponatraemia, hyperkalaemia and ECG abnormalities. The
      digoxin plasma concentration was 7.6 ug/l. The patient was given digoxin
      antibodies, following which the digoxin concentration was < 0.3 ug/l; 12 hours
      later the digoxin concentration was 3.1 ug/l as a result of redistribution; 2
      days after the administration of digoxin antibodies the plasma concentration was
      within the therapeutic range. 

PMID- 25944071
TI  - [A woman with abdominal pain after a meal].
AB  - A 57-year-old woman presented with pain in her upper right abdomen, since 3 days.
      Laboratory tests showed elevated inflammation markers and an increased amount of
      alkaline phosphatase. Abdominal CT showed a perforating object from the stomach,
      ending in the liver. Gastroscopy revealed that the object was a fish bone. 

PMID- 25944072
TI  - [For the critical reader: questions to ask about randomised trials].
AB  - The aim of this article is to provide guidance for the assessment of articles on
      randomised trials. This guide is intended for those who may want to apply the
      published results of randomised trials in everyday medical practice. In order to
      be able to attribute the observed differences in health outcomes between
      treatment groups with due certainty to the treatment being evaluated, it is
      necessary that the groups are comparable at the start of the study, during the
      study, and at the end of the study, i.e. when measuring the outcomes. In order to
      interpret the results of randomised trials and generalise these results to
      clinical practice, it is also necessary to consider the purpose of the study, the
      comparison that is made, the magnitude and direction of the observed effect, and
      to whom that effect applies.

PMID- 25944073
TI  - Comparison of dexmedetomidine with on-demand midazolam versus midazolam alone for
      procedural sedation during endoscopic submucosal dissection of gastric tumor.
AB  - OBJECTIVE: Endoscopic submucosal dissection (ESD) is commonly performed as a
      treatment for gastric neoplasms. However, sedation with midazolam (MDZ) often
      does not reach satisfactory sedation levels during the procedure and the drug may
      suppress respiration and blood pressure. This study aimed to investigate the
      safety and efficacy of dexmedetomidine (DEX) with on-demand MDZ (the DEX group)
      in comparison with MDZ alone (the MDZ group) as a sedative during ESD of gastric
      neoplasms. METHODS: Eighty patients undergoing ESD for gastric tumor were
      randomly assigned to one of two treatment regimens (40 patients in each). We
      investigated the depth of sedation by using a Modified Observers Assessment
      Alertness/Sedation score, the number of patients' reactions interfering with the
      procedure, sedation related-adverse events and the degree of satisfaction of
      patients and doctors. RESULTS: There was no statistically significant difference
      between the two groups regarding their age, gender, body mass index, American
      Society of Anesthesiologists physical status classification and the
      characteristics of the tumor. Appropriate sedation rate and the degree of
      satisfaction of the doctors were significantly higher in the DEX group than in
      the MDZ group. Patients' reactions interfering with the procedure were more
      numerous in the MDZ group than in the DEX group. There was no significant
      difference in adverse events between the two groups. CONCLUSIONS: DEX with on
      demand MDZ for sedation during gastric ESD is as safe as MDZ alone and the
      sedation effect of DEX with MDZ is superior to that of MDZ alone.

PMID- 25944074
TI  - Punctal function in lacrimal drainage: the 'pipette sign' and functional
      ectropion.
AB  - BACKGROUND: The aim was to assess the movements of the inferior punctum during
      blinking and discuss pertinent clinical applications. METHODS: This is a
      prospective, non-comparative observational case-series examining the function of
      inferior punctum during blinking using video recordings of the blinking action at
      the slitlamp with slow-motion analysis and comparison. RESULTS: In all 56 eyes of
      28 patents, supero-medial movement of the lower punctum toward the medial
      canthus, together with a medially directed protrusion of the inferior punctum was
      noted. It was also noted that the punctum blanched during this projectile
      movement compared to the rest of the lid margin. Simultaneous posterior rotation
      of the punctum was also observed in 48 eyes (85.7 per cent; 23 right eyes and 25
      left eyes), resulting in apposition of the punctum to the lacus lacrimalis. In
      eight eyes (14.3 per cent; five right eyes and three left) from six patients, co
      existence of medial punctal ectropion led to failure of internal rotation of the
      punctum during blinking, even though punctal 'pipette formation' was preserved.
      These six patients all suffered from epiphora in the affected eyes. The presence
      of 'pipette' formation was calculated to have a sensitivity of 80 per cent and
      specificity of 100 per cent for punctal ectropion in our series. A two-tailed
      Fisher exact test showed that based on our 56 eyes, these results were
      statistically significant (p < 0.0001). CONCLUSIONS: The inferior punctum plays
      an active and important role in the drainage of tears by the mechanism of supero
      medial movement and medially directed protrusion ('pipetting action'), failure of
      which contributes to epiphora. This is a highly specific sign and should be
      sought in the evaluation of epiphora, even in the absence of frank ectropion. In
      punctual stenosis where location of the punctal orifice is proving difficult,
      inducing the pipette sign will help in its identification.

PMID- 25944075
TI  - Copper-catalyzed alpha-selective hydrostannylation of alkynes for the synthesis
      of branched alkenylstannanes.
AB  - A variety of branched alkenylstannanes can directly be synthesized with excellent
      alpha-selectivity by the copper-catalyzed hydrostannylation using a distannane or
      a silylstannane, irrespective of the electronic and steric characteristics of
      terminal alkynes employed. Synthetic utility of the resulting branched
      alkenylstannane has been demonstrated by the total synthesis of bexarotene. 

PMID- 25944076
TI  - Neonatal case of novel KMT2D mutation in Kabuki syndrome with severe
      hypoglycemia.
AB  - A newborn Japanese girl with Kabuki syndrome had neonatal persistent
      hyperinsulinemic hypoglycemia, which seemed to be a rare complication of Kabuki
      syndrome. On sequence analysis she was found to have a novel heterozygous KMT2D
      mutation. Diazoxide therapy was effective for the hypoglycemia. Hypoglycemia
      should be considered when Kabuki syndrome patients have convulsion or other non
      specific symptoms. Diazoxide may help to improve hypoglycemia in patients with
      Kabuki syndrome complicated with hyperinsulinemic hypoglycemia. 

PMID- 25944077
TI  - The dimensional structure of the MacNew Health Related Quality of Life
      questionnaire: A Mokken Scale Analysis.
AB  - OBJECTIVE: The MacNew Health related Quality of Life Questionnaire is a widely
      used instrument for the assessment of health related quality of life in cardiac
      patients. The study addresses for the first time the dimensional structure of the
      MacNew with Mokken Scale Analysis (MSA). METHODS: Separate exploratory MSA of the
      MacNew was conducted in a large Spanish (n=1012) and a medium sized Austrian
      sample (n=262) of patients with Coronary Artery Disease (CAD) after Percutaneous
      Coronary Intervention (PCI). The results of both samples were summarized in a
      synthesis model. Confirmatory MSA and Confirmatory Factor Analysis (CFA) were
      used to evaluate the model. RESULTS: The synthesis model comprises 21 items
      forming a unidimensional sum scale of moderate strength. On the level of
      subdomains we define two strong unidimensional subscales (restriction: 6 items,
      and emotional: 10 items) and two smaller item sets (symptoms: 2 items and social:
      3 items). 5 items were excluded due to low scalability in both samples.
      CONCLUSION: Our results generally support the use of the MacNew Global score,
      with the limitation, that five items may be questionable with regard to
      scalability. On the level of unidimensional subscales MSA suggests to
      differentiate between a six-item restriction scale and a ten-item emotional
      scale. The study demonstrates that Mokken Scale Analysis complements the results
      of factor analysis and can contribute to a more comprehensive understanding of
      the dimensional structure of Health-related Quality of Life questionnaires.

PMID- 25944078
TI  - Alterations of tendons in diabetes mellitus: what are the current findings?
AB  - As a connective tissue, tendon connects the muscle and bone, and plays the key
      role in the locomotor system. Some previous studies have shown the pathological
      alternations in diabetic tendons, which might result in the structural and
      functional changes, and even accelerate the process of diabetic foot. In this
      review, we examined the current findings of the diabetic tendons in the form of
      various aspects, and summarized the clinical presentation, imaging,
      biomechanical, histopathological, cellular and molecular abnormalities in the
      diabetic tendons. The progress of diabetic tendon damage is complicated and the
      main hypotheses include the excessive accumulation of AGEs, the altered
      inflammatory response, neovascularization and insensitive neuropathy. However,
      the cellular and molecular mechanisms of these alterations are still ambiguous.
      Tendon stem/progenitor cells (TSPCs) have been discovered to play important roles
      in both tendon physiology and tendon pathology. Recently, we identified TSPCs
      from patellar tendons in our well-established diabetic rat model and found
      impaired tenogenic differentiation potential of these cells. We proposed a new
      hypothesis that the impaired cell functions of diabetic TSPCs might be the
      underlying cellular and molecular mechanism of the diabetic tendon alternations.
      These findings should be helpful to establish a better therapeutic strategy for
      diabetic tendon repair and regeneration. 

PMID- 25944079
TI  - Efficacy of mesenchymal stem cells injection for the management of knee
      osteoarthritis: a systematic review and meta-analysis.
AB  - OBJECTIVE: The purpose of this study was to access the efficacy of mesenchymal
      stem cells (MSCs) injection in the treatment of knee osteoarthritis (OA).
      METHODS: Studies were identified from databases (Pubmed, Embase, Cochrane
      Library, Biosis Previews, ClincalTrials.gov, CBMdisc) searched to December 2014
      using a battery of keywords. We included randomized controlled and controlled
      clinical trials of people with knee OA comparing the outcomes of pain and
      function for those receiving MSCs injection with those receiving no MSCs
      injection. Two reviewers independently selected studies, extracted relevant data
      and assessed study quality. Data were pooled and meta-analyses were performed.
      RESULTS: Seven randomized controlled and controlled clinical trials, studying a
      total of 314 participants with a diagnosis of knee OA were included. Overall,
      MSCs injection has no significant effect on pain [weighted mean difference (WMD)
      (95 % confidence interval (CI)) [-1.33(-3.08, 0.41), P = 0.13], and tends to
      improve self-reported physical function [standardized mean difference (SMD) (CI)
      = 2.35(0.92, 3.77), P = 0.001] at the last follow-up. But results from two high
      quality trials (94 patients) show a positive effect of MSCs injection on pain
      [WMD(CI) = -0.49 (-0.79, -0.19), P = 0.001]. Heterogeneity observed between
      studies regarding the effect of MSCs injection on pain and function was explained
      by the difference of follow-up time, outcome measures, control group, the source
      and dose of MSCs. The quality of evidence supporting these effect estimates was
      rated as low. CONCLUSION: MSCs injection could be potentially efficacious for
      decreasing pain and may improve physical function in patients with knee OA. The
      findings of this review should be confirmed using methodologically rigorous and
      adequately powered clinical trials.

PMID- 25944080
TI  - Utility of SAM68 in the progression and prognosis for bladder cancer.
AB  - BACKGROUND: Muscle invasive bladder cancer (MIBC) is often lethal and non-MIBC
      (NMIBC) can recur and progress, yet prognostic markers are currently inadequate.
      SAM68, a member of RNA-binding proteins, has been reported to contribute to
      progression of other cancers. The aim of this study is to investigate the
      potential utility of SAM68 in the progression and prognosis of bladder cancer.
      METHODS: Quantitative PCR and immunohistochemistry were utilized to examine the
      expression of SAM68 in ten pairs of MIBC and adjacent normal bladder urothelium,
      and eight pairs of MIBC and non-MIBC (NMIBC) tissues from the same patient.
      Moreover, SAM68 protein expression level and localization were examined by
      immunohistochemistry in 129 clinicopathologically characterized MIBC samples.
      Prognostic associations were determined by multivariable analysis incorporating
      standard prognostic factors. RESULTS: SAM68 expression was elevated in MIBC
      tissues compared with adjacent normal bladder urothelium, and was increased at
      both transcriptional and translational levels in MIBC tissues compared with NMIBC
      tissues of the same patient. For MIBC, high expression and nucleus-cytoplasm co
      expression of SAM68 were associated with higher T-stage, higher N-stage and worse
      recurrence-free survival. Five-year recurrence-free survival was 80% and 52.9%
      for MIBC patients with low and high SAM68 expression, respectively (p = 0.001).
      SAM68 nucleus-cytoplasm co-expression associated with worse 5-year recurrence
      free survival rate (49.2%) than SAM68 expression confined to the nucleus (82.5%)
      or cytoplasm (75.5%) alone. On multivariable analysis SAM68 expression level,
      SAM68 nucleus-cytoplasm co-expression, T-stage, and N-stage were all independent
      prognostic factors for recurrence-free survival of MIBC patients. CONCLUSIONS:
      SAM68 expression is increased in MIBC when compared to normal urothelium and
      NMIBC, and appears to be a potentially useful prognostic marker for MIBC.

PMID- 25944082
TI  - Reducing Monte Carlo error in the Bayesian estimation of risk ratios using log
      binomial regression models.
AB  - In cohort studies, binary outcomes are very often analyzed by logistic
      regression. However, it is well known that when the goal is to estimate a risk
      ratio, the logistic regression is inappropriate if the outcome is common. In
      these cases, a log-binomial regression model is preferable. On the other hand,
      the estimation of the regression coefficients of the log-binomial model is
      difficult owing to the constraints that must be imposed on these coefficients.
      Bayesian methods allow a straightforward approach for log-binomial regression
      models and produce smaller mean squared errors in the estimation of risk ratios
      than the frequentist methods, and the posterior inferences can be obtained using
      the software WinBUGS. However, Markov chain Monte Carlo methods implemented in
      WinBUGS can lead to large Monte Carlo errors in the approximations to the
      posterior inferences because they produce correlated simulations, and the
      accuracy of the approximations are inversely related to this correlation. To
      reduce correlation and to improve accuracy, we propose a reparameterization based
      on a Poisson model and a sampling algorithm coded in R.

PMID- 25944081
TI  - An international multicenter retrospective study of Pseudomonas aeruginosa
      nosocomial pneumonia: impact of multidrug resistance.
AB  - INTRODUCTION: Pseudomonas aeruginosa nosocomial pneumonia (Pa-NP) is associated
      with considerable morbidity, prolonged hospitalization, increased costs, and
      mortality. METHODS: We conducted a retrospective cohort study of adult patients
      with Pa-NP to determine 1) risk factors for multidrug-resistant (MDR) strains and
      2) whether MDR increases the risk for hospital death. Twelve hospitals in 5
      countries (United States, n = 3; France, n = 2; Germany, n = 2; Italy, n = 2; and
      Spain, n = 3) participated. We compared characteristics of patients who had MDR
      strains to those who did not and derived regression models to identify predictors
      of MDR and hospital mortality. RESULTS: Of 740 patients with Pa-NP, 226 patients
      (30.5%) were infected with MDR strains. In multivariable analyses, independent
      predictors of multidrug-resistance included decreasing age (adjusted odds ratio
      [AOR] 0.91, 95% confidence interval [CI] 0.96-0.98), diabetes mellitus (AOR 1.90,
      95% CI 1.21-3.00) and ICU admission (AOR 1.73, 95% CI 1.06-2.81). Multidrug
      resistance, heart failure, increasing age, mechanical ventilation, and bacteremia
      were independently associated with in-hospital mortality in the Cox Proportional
      Hazards Model analysis. CONCLUSIONS: Among patients with Pa-NP the presence of
      infection with a MDR strain is associated with increased in-hospital mortality.
      Identification of patients at risk of MDR Pa-NP could facilitate appropriate
      empiric antibiotic decisions that in turn could lead to improved hospital
      survival.

PMID- 25944083
TI  - Comparative 16S rRNA signatures and multilocus sequence analysis for the genus
      Salinicola and description of Salinicola acroporae sp. nov., isolated from coral
      Acropora digitifera.
AB  - A novel Gram-negative, aerobic, motile marine bacterium, strain S4-41(T), was
      isolated from mucus of the coral Acropora digitifera from the Andaman Sea.
      Heterotrophic growth was observed in 0-25 % NaCl, at 15-45  degrees C and pH 4.5
      9. In phylogenetic trees, strain S4-41(T) was grouped within the genus Salinicola
      but formed a separate branch distant from a cluster composed of Salinicola
      salarius M27(T) and Salinicola socius SMB35(T). DNA-DNA relatedness between
      strain S4-41(T) and these reference strains were well below 70 %. Q-9 was the
      sole respiratory quinone. The DNA G+C content was determined to be 63.6 mol%.
      Based on a polyphasic analysis, strain S4-41(T) is concluded to represent a novel
      species in the genus Salinicola for which the name Salinicola acroporae sp. nov.
      is proposed. The type strain is S4-41(T) (=JCM 30412(T) = LMG 28587(T)).
      Comparative 16S rRNA analysis of the genera Salinicola, Kushneria,
      Chromohalobacter and Cobetia revealed the presence of genus specific sequence
      signatures. Multilocus sequence analysis based on concatenated sequences of rRNAs
      (16S and 23S) and four protein coding housekeeping genes (atpA, gyrB, secA, rpoD)
      was found to be unnecessary for phylogenetic studies of the genus Salinicola.

PMID- 25944084
TI  - Actinomadura amylolytica sp. nov. and Actinomadura cellulosilytica sp. nov.,
      isolated from geothermally heated soil.
AB  - Two aerobic, Gram-positive actinomycetes, designated YIM 77502(T) and YIM
      77510(T), were isolated from geothermally heated soil of Tengchong county, Yunnan
      province, south-west China. The taxonomic position of strains YIM 77502(T) and
      YIM 77510(T) were investigated by a polyphasic approach. Phylogenetic analyses
      based on 16S rRNA gene sequences showed that strains YIM 77502(T) and YIM
      77510(T) belong to the genus Actinomadura. Both strains form extensively-branched
      substrate and aerial mycelia which differentiated into short spore chains. The
      cell wall of the two strains contained meso-diaminopimelic acid, while the whole
      cell sugars detected were glucose, madurose, mannose and rhamnose. The polar
      lipid profile of strain YIM 77502(T) was found to consist of
      diphosphatidylglycerol, phosphatidylinositol mannoside, phosphatidylinositol, two
      unidentified phospholipids and an unidentified polar lipid, while strain YIM
      77510(T) consisted of diphosphatidylglycerol, phosphatidylinositol mannoside and
      phosphatidylinositol. The respiratory quinones of strains YIM 77502(T) and YIM
      77510(T) were MK-9(H6) and MK-9(H8). The major fatty acids (>10 %) of strain YIM
      77502(T) were C17:0, iso-C16:0, C17:010-methyl and iso-C18:0, and those of strain
      YIM 77510(T) were iso-C16:0, C17:010-methyl and iso-C18:0. The G+C contents of
      strains YIM 77502(T) and YIM 77510(T) were determined to be 71.3 and 70.2 mol%,
      respectively. The DNA-DNA hybridization values of strains YIM 77502(T), YIM
      77510(T) and their closest phylogenetic neighbours Actinomadura echinospora BCRC
      12547(T) and Actinomadura umbrina KCTC 9343(T) were less than 70 %. Based on the
      morphological and physiological properties, and phylogenetic analyses, strains
      YIM 77502(T) and YIM 77510(T) are considered to represent two novel species of
      the genus Actinomadura, for which the names Actinomadura amylolytica sp. nov.
      (type strain YIM 77502(T) = DSM 45822(T) = CCTCC AA 2012024(T)) and Actinomadura
      cellulosilytica sp. nov. (type strain YIM 77510(T) = DSM 45823(T) = CCTCC AA
      2012023(T)) are proposed.

PMID- 25944085
TI  - If you don't use it you'll likely lose it.
AB  - This article is a commentary on the recently published manuscript by Drey et al.
      (2014). The age-related loss of motor units (MU) is an immutable process and
      understanding the possible role of physical activity in maintaining functional
      MUs is an important topic. Dysfunctional remodelling of a MU is associated with
      denervation of the muscle and ultimate death of the spinal motoneurone.
      Conversely, in cross-sectional studies, high levels of physical activity in
      humans report a maintenance in the number of functional MUs in older master
      runners. However, it seems that only those MUs directly associated with the
      elevated long-term physical activity appear to benefit from any exercise-induced
      neuroprotective effect.

PMID- 25944086
TI  - A novel path of improving heart function after infarction.

PMID- 25944087
TI  - Curcumin induces M2 macrophage polarization by secretion IL-4 and/or IL-13.
AB  - AIMS: To address the underlying mechanisms by which curcumin facilitates M2
      phenotype polarization of macrophages and its roles in the protective effects
      during experimental autoimmune myocarditis (EAM). METHODS AND RESULTS: The
      expression of classic M2 markers, including macrophage mannose receptor (MMR),
      arginase-1 (Arg-1) and peroxisome proliferator-activated receptor-gamma (PPAR
      gamma) was upregulated in curcumin-treated Raw264.7 macrophages. Curcumin
      increased interleukin-4 (IL-4) and interleukin-13 (IL-13) mRNA expression and
      protein secretion. Curcumin notably increased STAT6 phosphorylation. Leflunomide,
      a STAT6 inhibitor, and IL-4 and/or IL-13 neutralizing antibodies antagonized the
      induction of MMR, Arg-1 and PPAR-gamma by curcumin in Raw264.7 cells. In vivo, 6
      week old male Lewis rats were used to induce EAM and orally administrated with
      curcumin or corn oil for 3weeks after myosin injection. Cardiac functional
      parameters, including left ventricular fractional shortening (LVFS), ejection
      fraction (EF), left ventricular end-systolic diameter (LVEDs) and heart rate (HR)
      were significantly improved by curcumin treatment. Curcumin also reduced the
      inflammatory cell infiltration and myocardial mRNA levels of interleukin-1beta
      (IL-1beta) and inducible nitric oxide synthase (iNOS). Meanwhile, the myocardial
      mRNA levels of MMR and Arg-1 were markedly up-regulated by curcumin.
      Immunofluorescence assay showed that the number of CD68(+) MMR(+) and CD68(+) Arg
      1(+) double positive macrophages in curcumin-treated myocardial tissue was
      significantly higher than untreated control. The number of CD68(+) iNOS(+) double
      positive macrophages was increased obviously in EAM group, but decreased markedly
      by curcumin treatment. CONCLUSIONS: Taken together, these results show that
      curcumin induces macrophage M2 polarization by secretion of IL-4 and/or IL-13.
      Curcumin ameliorates EAM by reducing infiltration inflammatory macrophages and by
      polarizing M0 and M1 macrophages to M2 phenotype.

PMID- 25944088
TI  - Interplay between the E2F pathway and beta-adrenergic signaling in the
      pathological hypertrophic response of myocardium.
AB  - The E2F/Pocket protein (Rb) pathway regulates cell growth, differentiation, and
      death by modulating gene expression. We previously examined this pathway in the
      myocardium via manipulation of the unique E2F repressor, E2F6, which is believed
      to repress gene activity independently of Rb. Mice with targeted expression of
      E2F6 in postnatal myocardium developed dilated cardiomyopathy (DCM) without
      hypertrophic growth. We assessed the mechanisms of the apparent failure of
      compensatory hypertrophic growth as well as their response to the beta-adrenergic
      agonist isoproterenol. As early as 2 weeks, E2F6 transgenic (Tg) mice present
      with dilated thinner left ventricles and significantly reduced ejection fraction
      and fractional shortening which persists at 6 weeks of age, but with no apparent
      increase in left ventricle weight: body weight (LVW:BW). E2F6-Tg mice treated
      with isoproterenol (6.1 mg/kg/day) show double the increase in LVW:BW than their
      Wt counterparts (32% vs 16%, p-value: 0.007). Western blot analysis revealed the
      activation of the adrenergic pathway in Tg heart tissue under basal conditions
      with ~2-fold increase in the level of beta2-adrenergic receptors (p-value: 8.9E
      05), protein kinase A catalytic subunit (PKA-C) (p-value: 0.0176), activated c
      Src tyrosine-protein kinase (p-value: 0.0002), extracellular receptor kinase 2
      (ERK2) (p-value: 0.0005), and induction of the anti-apoptotic protein Bcl2 (p
      value 0. 0.00001). In contrast, a ~60% decrease in the cardiac growth regulator:
      AKT1 (p-value 0.0001) and a ~four fold increase in cyclic AMP dependent
      phosphodiesterase 4D (PDE4D), the negative regulator of PKA activity, were
      evident in the myocardium of E2F6-Tg mice. The expression of E2F3 was down
      regulated by E2F6, but was restored by isoproterenol. Further, Rb expression was
      down-regulated in Tg mice in response to isoproterenol implying a net activation
      of the E2F pathway. Thus the unique regulation of E2F activity by E2F6 renders
      the myocardium hypersensitive to adrenergic stimulus resulting in robust
      hypertrophic growth. These data reveal a novel interplay between the E2F pathway,
      beta2-adrenergic/PKA/PDE4D, and ERK/c-Src axis in fine tuning the pathological
      hypertrophic growth response. E2F6 deregulates E2F3 such that pro-hypertrophic
      growth and survival are enhanced via beta2-adrenergic signaling however this
      response is outweighed by the induction of anti-hypertrophic signals so that left
      ventricle dilation proceeds without any increase in muscle mass.

PMID- 25944091
TI  - Optimization of Extraction, HPLC and Kinetic Studies for Determination of Some
      Food Tainting Compounds in Different Food Matrices.
AB  - Solid-liquid extraction, ultrasonic-assisted extraction and matrix solid-phase
      dispersion (MSPD) were optimized and compared in terms of recoveries for the
      simultaneous extraction of indole (IND) and 2,4-dichlorophenol (DCP) from catfish
      samples and for the extraction of IND alone from potato samples. Applying high
      performance liquid chromatography (HPLC-DAD) procedure using mobile phase of
      methanol : water (65 : 35) at 280 nm, MSPD was the method of choice for the
      extraction of IND and DCP from catfish and, also, for IND from potato. The
      extraction recoveries of MSPD were in the range (97.9-99.7%) and (99.8-100.6%);
      for IND and DCP, respectively, in catfish samples and (98.4-99.7%) for IND alone
      in potato samples. Solid-phase extraction (SPE) was chosen the method of choice
      for the extraction of DCP from fish farms water samples after optimization and
      comparison with direct sample injection and extraction recoveries were in the
      range (97.9-100.3%). Kinetics were further studied to follow each of production
      of IND in catfish during storage at different temperatures and uptake of DCP by
      tilapia in fish farms water samples using MSPD-HPLC and SPE-HPLC, respectively. 

PMID- 25944092
TI  - Temporal assessment of vascular reactivity and functionality using MRI during
      postischemic proangiogenenic vascular remodeling.
AB  - Postischemic angiogenesis is an important recovery mechanism. Both arteries and
      veins are upregulated during angiogenesis, but eventually there are more
      angiogenic veins than arteries in terms of number and length. It is critical to
      understand how the veins are modulated after ischemia and then transitioned into
      angiogenic vessels during the proangiogenic stage to finally serve as a
      restorative strength to the injured area. Using a rat model of transient focal
      cerebral ischemia, the hypercapnic blood oxygen level-dependent (BOLD) response
      was used to evaluate vascular reactivity, while the hyperoxic BOLD and tissue
      oxygen level-dependent (TOLD) responses were used to evaluate the vascular
      functionality at 1, 3, and 7days after ischemia. Vessel-like venous signals
      appeared on R2* maps on days 3 and 7, but not on day 1. The large hypercapnic
      BOLD responses on days 3 and 7 indicated that these areas have high vascular
      reactivity. The temporal correlation between vascular reactivity and the
      immunoreactivity to desmin and VEGF further indicates that the integrity of
      vascular reactivity is associated with the pericyte coverage as regulated by the
      VEGF level. Vascular functionality remained low on days 1, 3, and 7, as reflected
      by the small hyperoxic BOLD and large hyperoxic TOLD responses, indicating the
      low oxygen consumption of the ischemic tissues. These functional changes in
      proangiogenic veins may be critical for angiogenesis. 

PMID- 25944090
TI  - Oligocene niche shift, Miocene diversification - cold tolerance and accelerated
      speciation rates in the St. John's Worts (Hypericum, Hypericaceae).
AB  - BACKGROUND: Our aim is to understand the evolution of species-rich plant groups
      that shifted from tropical into cold/temperate biomes. It is well known that
      climate affects evolutionary processes, such as how fast species diversify,
      species range shifts, and species distributions. Many plant lineages may have
      gone extinct in the Northern Hemisphere due to Late Eocene climate cooling, while
      some tropical lineages may have adapted to temperate conditions and radiated; the
      hyper-diverse and geographically widespread genus Hypericum is one of these.
      RESULTS: To investigate the effect of macroecological niche shifts on
      evolutionary success we combine historical biogeography with analyses of
      diversification dynamics and climatic niche shifts in a phylogenetic framework.
      Hypericum evolved cold tolerance c. 30 million years ago, and successfully
      colonized all ice-free continents, where today ~500 species exist. The other
      members of Hypericaceae stayed in their tropical habitats and evolved into ~120
      species. We identified a 15-20 million year lag between the initial change in
      temperature preference in Hypericum and subsequent diversification rate shifts in
      the Miocene. CONCLUSIONS: Contrary to the dramatic niche shift early in the
      evolution of Hypericum most extant species occur in temperate climates including
      high elevations in the tropics. These cold/temperate niches are a distinctive
      characteristic of Hypericum. We conclude that the initial release from an
      evolutionary constraint (from tropical to temperate climates) is an important
      novelty in Hypericum. However, the initial shift in the adaptive landscape into
      colder climates appears to be a precondition, and may not be directly related to
      increased diversification rates. Instead, subsequent events of mountain formation
      and further climate cooling may better explain distribution patterns and species
      richness in Hypericum. These findings exemplify important macroevolutionary
      patterns of plant diversification during large-scale global climate change.

PMID- 25944093
TI  - [Nationwide evaluation of German university teaching methods in neurology].
AB  - BACKGROUND: Germany is confronted with a lack of medical doctors and an
      increasing need for neurologists in particular. In order to recruit future
      doctors in neurology it is essential to attract young students when still at
      university. OBJECTIVES: This article presents the first German national survey of
      medical students' acceptance of teaching methods in neurology. The participants
      evaluated teaching methods and examination formats and were asked about their
      preferences. MATERIAL AND METHODS: The survey was based on a questionnaire
      distributed to 22 German medical schools and 1245 participating students.
      RESULTS: Interactive teaching methods, especially courses in practical
      examinations, clinical internships and bedside teaching were highly rated among
      the students. In contrast, multiple choice tests, as one of the most widespread
      examination methods, were poorly rated compared to practical and oral
      examinations. For most of the students it was not decisive, in which semester
      teaching of neurology took place, while the majority asked for additional and
      more intensive neurological education. CONCLUSION: The data give an overview of
      teaching of neurology in Germany and students' assessment of various approaches.
      The results should be utilized towards reorientation of future curricula that
      should aim at innovative and even more practically oriented teaching.

PMID- 25944095
TI  - Ion-exchange vs reversed-phase chromatography for separation and determination of
      basic psychotropic drugs.
AB  - Ion exchange chromatography, an alternative to reversed-phase (RP)
      chromatography, is described in this paper. We aimed to obtain optimal conditions
      for the separation of basic drugs because silica-based RP stationary phases show
      silanol effect and make the analysis of basic analytes hardly possible. The
      retention, separation selectivity, symmetry of peaks and system efficiency were
      examined in different eluent systems containing different types of buffers at
      acidic pH and with the addition of organic modifiers: methanol and acetonitrile.
      The obtained results reveal a large influence of the salt cation used for buffer
      preparation and the type of organic modifier on the retention behavior of the
      analytes. These results were also compared with those obtained on an XBridge C18
      column. The obtained results demonstrated that SCX stationary phases can be
      successfully used as alternatives to C18 stationary phases in the separation of
      basic compounds. The most selective and efficient chromatographic systems were
      applied for the quantification of some psychotropic drugs in fortified human
      serum samples.

PMID- 25944094
TI  - International Regulations of Propolis Quality: Required Assays do not Necessarily
      Reflect their Polyphenolic-Related In Vitro Activities.
AB  - Propolis has been proposed as a polyphenolic-rich natural product potentially
      able to be used for human consumption or even for medicinal proposes. To
      guarantee a minimum phenolic and flavonoid content and as consequence of their
      related-biological activities, international requirements of propolis quality are
      commonly applied. In this work we assessed phenolic and flavonoid contents of
      propolis; the antioxidant capacity (toward peroxyl radicals and hypochlorous
      acid); the ability to generate nitric oxide (NO); and, finally the antimicrobial
      activity of 6 propolis samples from the VI region of Chile. Our results show that
      the total phenolic and flavonoid content of propolis samples are not always in
      agreement with their polyphenolic-associated in vitro activities. For example,
      P03 and P06 samples showed the lowest (25 +/- 4 GAE/g propolis) and the highest
      (105 +/- 3 GAE/g propolis) total phenolic content, respectively. This was in
      agreement with flavonoid content and their Oxygen Radical Absorbance Capacity
      (ORAC) activity. However, this dependence was not observed toward HOCl, NO
      release and antimicrobial activity. Based on our results, we consider that, in
      order to guarantee the antioxidant or antimicrobial in vitro effects, the
      international regulations of propolis quality should contemplate the convenience
      of incorporating other simple analytical test such as ORAC or antimicrobial
      tests. 

PMID- 25944089
TI  - Olfactory dysfunction: its early temporal relationship and neural correlates in
      the pathogenesis of Alzheimer's disease.
AB  - We interact with the physical world through our senses, and these aid our
      behavioral performance and various activities of life. Sensory information is
      transmitted in neuronal networks, and the brain optimally interprets the external
      and internal milieu/environment. This paper delineates the framework in which the
      pathogenesis of memory and cognitive dysfunction is underpinned by sensory
      olfactory dysfunction. ERC is the gateway for olfactory input to the hippocampus,
      and there is seamless synchronization between sensory function and hippocampal
      activity. Transmission of olfactory information to the hippocampus is sequential
      it is projected from the olfactory receptors to olfactory bulb to the primary
      olfactory cortex (comprised the anterior olfactory nucleus, the olfactory
      tubercle, and the piriform cortex) to the entorhinal cortex (ERC). Through
      perforant pathway ERC enables olfactory inputs to effectively excite hippocampal
      neurons. One of the earliest pathological changes in Alzheimer's disease (AD)
      include the olfactory dysfunction and the atrophy in ERC and hippocampus (rate in
      ERC is higher than in the hippocampus). Olfactory dysfunction negatively impacts
      the ERC and the deafferenting of the hippocampus from olfactory inputs
      upregulates memory decline. Olfactory dysfunction, therefore, is an important and
      early correlate of AD pathology. A number of factors described here may cause
      olfactory dysfunction; this may lead to hypoperfusion, hypometabolism, impaired
      synaptic transmission, and variable atrophy in olfaction-related regions.
      Improvement in olfactory function, therefore, is an important goal in order to
      attenuate cognitive neuropathology in aging and AD. This article seeks to provide
      a comprehensive and balanced overview of olfactory neuropathology in incipient
      AD, and suggests strategies to enhance olfactory function and ameliorate
      cognitive decline. 

PMID- 25944096
TI  - Prenatal diagnosis and findings of tetrasomy 9p.
AB  - Tetrasomy 9p is a rare condition initially reported by Ghymers et al. Reported
      cases are a mix of prenatal and neonatal/pediatric cases in non-mosaic and mosaic
      cases. We report on the common mechanism leading to this form of chromosome
      abnormality, the various types of tetrasomy 9p as well as the prenatal
      sonographic and laboratory presentation of our case and previously reported cases
      with mosaic and non-mosaic tetrasomy 9p. From these reported cases, a
      recognizable syndrome is emerging. Multiple fetal abnormalities amenable to
      ultrasound diagnosis are likely to be present. However, neither ultrasound study
      alone nor the first-trimester screen for the common aneuploidies can suggest the
      correct diagnosis. Chromosome study of more than a single tissue is necessary in
      order to establish the correct diagnosis and to differentiate between mosaic and
      non-mosaic tetrasomy 9p cases. 

PMID- 25944097
TI  - Impaired autophagy in mouse embryonic fibroblasts null for Kruppel-like Factor 4
      promotes DNA damage and increases apoptosis upon serum starvation.
AB  - BACKGROUND: Autophagy is a major cellular process by which cytoplasmic components
      such as damaged organelles and misfolded proteins are recycled. Although low
      levels of autophagy occur in cells under basal conditions, certain cellular
      stresses including nutrient depletion, DNA damage, and oxidative stress are known
      to robustly induce autophagy. Kruppel-like factor 4 (KLF4) is a zinc-finger
      transcription factor activated during oxidative stress to maintain genomic
      stability. Both autophagy and KLF4 play important roles in response to stress and
      function in tumor suppression. METHODS: To explore the role of KLF4 on autophagy
      in mouse embryonic fibroblasts (MEFs), we compared wild-type with Klf4 deficient
      cells. To determine the levels of autophagy, we starved MEFs for different times
      with Earle's balanced salts solution (EBSS). Rapamycin was used to manipulate
      mTOR activity and autophagy. The percentage of cells with gamma-H2AX foci, a
      marker for DNA damage, and punctate pattern of GFP-LC3 were counted by confocal
      microscopy. The effects of the drug treatments, Klf4 overexpression, or Klf4
      transient silencing on autophagy were analyzed using Western blot. Trypan Blue
      assay and flow cytometry were used to study cell viability and apoptosis,
      respectively. qPCR was also used to assay basal and the effects of Klf4
      overexpression on Atg7 expression levels. RESULTS: Here our data suggested that
      Klf4 (-/-) MEFs exhibited impaired autophagy, which sensitized them to cell death
      under nutrient deprivation. Secondly, DNA damage in Klf4-null MEFs increased
      after treatment with EBSS and was correlated with increased apoptosis. Thirdly,
      we found that Klf4 (-/-) MEFs showed hyperactive mTOR activity. Furthermore, we
      demonstrated that rapamycin reduced the increased level of mTOR in Klf4 (-/-)
      MEFs, but did not restore the level of autophagy. Finally, re-expression of Klf4
      in Klf4 deficient MEFs resulted in increased levels of LC3II, a marker for
      autophagy, and Atg7 expression level when compared to GFP-control transfected
      Klf4 (-/-) MEFs. CONCLUSION: Taken together, our results strongly suggest that
      KLF4 plays a critical role in the regulation of autophagy and suppression of mTOR
      activity. In addition, we showed that rapamycin decreased the level of mTOR in
      Klf4 (-/-) MEFs, but did not restore autophagy. This suggests that KLF4 regulates
      autophagy through both mTOR-dependent and independent mechanisms. Furthermore,
      for the first time, our findings provide novel insights into the mechanism by
      which KLF4 perhaps prevents DNA damage and apoptosis through activation of
      autophagy.

PMID- 25944098
TI  - Role of aminoalcoholphosphotransferases 1 and 2 in phospholipid homeostasis in
      Arabidopsis.
AB  - Aminoalcoholphosphotransferase (AAPT) catalyzes the synthesis of
      phosphatidylcholine (PC) and phosphotidylethanolamine (PE), which are the most
      prevalent membrane phospholipids in all eukaryotic cells. Here, we show that
      suppression of AAPTs results in extensive membrane phospholipid remodeling in
      Arabidopsis thaliana. Double knockout (KO) mutants that are hemizygous for either
      aapt1 or aapt2 display impaired pollen and seed development, leading to embryotic
      lethality of the double KO plants, whereas aapt1 or aapt2 single KO plants show
      no overt phenotypic alterations. The growth rate and seed yield of AAPT RNA
      interference (RNAi) plants are greatly reduced. Lipid profiling shows decreased
      total galactolipid and phospholipid content in aapt1-containing mutants,
      including aapt1, aapt1/aapt1 aapt2/AAPT2, aapt1/AAPT1 aapt2/aapt2, and AAPT RNAi
      plants. The level of PC in leaves was unchanged, whereas that of PE was reduced
      in all AAPT-deficient plants, except aapt2 KO. However, the acyl species of PC
      was altered, with increased levels of C34 species and decreased C36 species.
      Conversely, the levels of PE and phosphatidylinositol were decreased in C34
      species. In seeds, all AAPT-deficient plants, including aapt2 KO, displayed a
      decrease in PE. The data show that AAPT1 and AAPT2 are essential to plant
      vegetative growth and reproduction and have overlapping functions but that AAPT1
      contributes more than AAPT2 to PC production in vegetative tissues. The opposite
      changes in molecular species between PC and PE and unchanged PC level indicate
      the existence of additional pathways that maintain homeostatic levels of PC,
      which are crucial for the survival and proper development of plants. 

PMID- 25944099
TI  - The Control of Arabidopsis thaliana Growth by Cell Proliferation and
      Endoreplication Requires the F-Box Protein FBL17.
AB  - A key step of the cell cycle is the entry into the DNA replication phase that
      typically commits cells to divide. However, little is known about the molecular
      mechanisms regulating this transition in plants. Here, we investigated the
      function of FBL17 (F BOX-LIKE17), an Arabidopsis thaliana F-box protein
      previously shown to govern the progression through the second mitosis during
      pollen development. Our work reveals that FBL17 function is not restricted to
      gametogenesis. FBL17 transcripts accumulate in both proliferating and postmitotic
      cell types of Arabidopsis plants. Loss of FBL17 function drastically reduces
      plant growth by altering cell division activity in both shoot and root apical
      meristems. In fbl17 mutant plants, DNA replication is severely impaired and
      endoreplication is fully suppressed. At the molecular level, lack of FBL17
      increases the stability of the CDK (CYCLIN-DEPENDENT KINASE) inhibitor KIP
      RELATED PROTEIN2 known to switch off CDKA;1 kinase activity. Despite the strong
      inhibition of cell proliferation in fbl17, some cells are still able to enter S
      phase and eventually to divide, but they exhibit a strong DNA damage response and
      often missegregate chromosomes. Altogether, these data indicate that the F-box
      protein FBL17 acts as a master cell cycle regulator during the diploid sporophyte
      phase of the plant. 

PMID- 25944100
TI  - Autophagic recycling plays a central role in maize nitrogen remobilization.
AB  - Autophagy is a primary route for nutrient recycling in plants by which
      superfluous or damaged cytoplasmic material and organelles are encapsulated and
      delivered to the vacuole for breakdown. Central to autophagy is a conjugation
      pathway that attaches AUTOPHAGY-RELATED8 (ATG8) to phosphatidylethanolamine,
      which then coats emerging autophagic membranes and helps with cargo recruitment,
      vesicle enclosure, and subsequent vesicle docking with the tonoplast. A key
      component in ATG8 function is ATG12, which promotes lipidation upon its
      attachment to ATG5. Here, we fully defined the maize (Zea mays) ATG system
      transcriptionally and characterized it genetically through atg12 mutants that
      block ATG8 modification. atg12 plants have compromised autophagic transport as
      determined by localization of a YFP-ATG8 reporter and its vacuolar cleavage
      during nitrogen or fixed-carbon starvation. Phenotypic analyses showed that atg12
      plants are phenotypically normal and fertile when grown under nutrient-rich
      conditions. However, when nitrogen-starved, seedling growth is severely arrested,
      and as the plants mature, they show enhanced leaf senescence and stunted ear
      development. Nitrogen partitioning studies revealed that remobilization is
      impaired in atg12 plants, which significantly decreases seed yield and nitrogen
      harvest index. Together, our studies demonstrate that autophagy, while
      nonessential, becomes critical during nitrogen stress and severely impacts maize
      productivity under suboptimal field conditions. 

PMID- 25944101
TI  - HEMERA Couples the Proteolysis and Transcriptional Activity of PHYTOCHROME
      INTERACTING FACTORs in Arabidopsis Photomorphogenesis.
AB  - Phytochromes (phys) are red and far-red photoreceptors that control plant
      development and growth by promoting the proteolysis of a family of
      antagonistically acting basic helix-loop-helix transcription factors, the
      PHYTOCHROME-INTERACTING FACTORs (PIFs). We have previously shown that the
      degradation of PIF1 and PIF3 requires HEMERA (HMR). However, the biochemical
      function of HMR and the mechanism by which it mediates PIF degradation remain
      unclear. Here, we provide genetic evidence that HMR acts upstream of PIFs in
      regulating hypocotyl growth. Surprisingly, genome-wide analysis of HMR- and PIF
      dependent genes reveals that HMR is also required for the transactivation of a
      subset of PIF direct-target genes. We show that HMR interacts with all PIFs. The
      HMR-PIF interaction is mediated mainly by HMR's N-terminal half and PIFs'
      conserved active-phytochrome B binding motif. In addition, HMR possesses an
      acidic nine-amino-acid transcriptional activation domain (9aaTAD) and a loss-of
      function mutation in this 9aaTAD impairs the expression of PIF target genes and
      the destruction of PIF1 and PIF3. Together, these in vivo results support a
      regulatory mechanism for PIFs in which HMR is a transcriptional coactivator
      binding directly to PIFs and the 9aaTAD of HMR couples the degradation of PIF1
      and PIF3 with the transactivation of PIF target genes. 

PMID- 25944104
TI  - Retinoid resistance and multifaceted impairment of retinoic acid synthesis in
      glioblastoma.
AB  - Measuring concentrations of the differentiation-promoting hormone retinoic acid
      (RA) in glioblastoma tissues would help to understand the reason why RA treatment
      has been inefficient in clinical trials involving brain tumor patients. Here, we
      apply a recently established extraction and measurement protocol to screen
      glioblastoma tissues for the levels of the RA precursor retinol and biologically
      active RA. Combining this approach with mRNA analyses of 26 tumors and 8 normal
      brains, we identify a multifaceted disturbance of RA synthesis in glioblastoma,
      involving multiple aldehyde dehydrogenase 1 family and retinol dehydrogenase
      enzymes. Through database studies and methylation analyses, we narrow down
      chromosomal deletions and aberrant promoter hypermethylation as potential
      mechanisms accounting for these alterations. Employing chromatin
      immunoprecipitation analyses and cell-culture studies, we further show that
      chromatin at RA target genes is poised to RA substitution, but most glioblastoma
      cell cultures are completely resistant to RA treatment. This paradoxical RA
      response is unrelated to alternative RA signaling through the fatty acid-binding
      protein 5/peroxisome proliferator-activated receptor delta axis. Our data suggest
      a multifaceted disturbance of RA synthesis in glioblastoma and contribute to
      reconsider current RA treatment strategies.

PMID- 25944105
TI  - Utilizing the Wikidata system to improve the quality of medical content in
      Wikipedia in diverse languages: a pilot study.
AB  - BACKGROUND: Wikipedia is an important source of medical information for both
      patients and medical professionals. Given its wide reach, improving the quality,
      completeness, and accessibility of medical information on Wikipedia could have a
      positive impact on global health. OBJECTIVE: We created a prototypical
      implementation of an automated system for keeping drug-drug interaction (DDI)
      information in Wikipedia up to date with current evidence about clinically
      significant drug interactions. Our work is based on Wikidata, a novel, graph
      based database backend of Wikipedia currently in development. METHODS: We set up
      an automated process for integrating data from the Office of the National
      Coordinator for Health Information Technology (ONC) high priority DDI list into
      Wikidata. We set up exemplary implementations demonstrating how the DDI data we
      introduced into Wikidata could be displayed in Wikipedia articles in diverse
      languages. Finally, we conducted a pilot analysis to explore if adding the ONC
      high priority data would substantially enhance the information currently
      available on Wikipedia. RESULTS: We derived 1150 unique interactions from the ONC
      high priority list. Integration of the potential DDI data from Wikidata into
      Wikipedia articles proved to be straightforward and yielded useful results. We
      found that even though the majority of current English Wikipedia articles about
      pharmaceuticals contained sections detailing contraindications, only a small
      fraction of articles explicitly mentioned interaction partners from the ONC high
      priority list. For 91.30% (1050/1150) of the interaction pairs we tested, none of
      the 2 articles corresponding to the interacting substances explicitly mentioned
      the interaction partner. For 7.21% (83/1150) of the pairs, only 1 of the 2
      associated Wikipedia articles mentioned the interaction partner; for only 1.48%
      (17/1150) of the pairs, both articles contained explicit mentions of the
      interaction partner. CONCLUSIONS: Our prototype demonstrated that automated
      updating of medical content in Wikipedia through Wikidata is a viable option,
      albeit further refinements and community-wide consensus building are required
      before integration into public Wikipedia is possible. A long-term endeavor to
      improve the medical information in Wikipedia through structured data
      representation and automated workflows might lead to a significant improvement of
      the quality of medical information in one of the world's most popular Web
      resources.

PMID- 25944102
TI  - Inference of the Arabidopsis lateral root gene regulatory network suggests a
      bifurcation mechanism that defines primordia flanking and central zones.
AB  - A large number of genes involved in lateral root (LR) organogenesis have been
      identified over the last decade using forward and reverse genetic approaches in
      Arabidopsis thaliana. Nevertheless, how these genes interact to form a LR
      regulatory network largely remains to be elucidated. In this study, we developed
      a time-delay correlation algorithm (TDCor) to infer the gene regulatory network
      (GRN) controlling LR primordium initiation and patterning in Arabidopsis from a
      time-series transcriptomic data set. The predicted network topology links the
      very early-activated genes involved in LR initiation to later expressed cell
      identity markers through a multistep genetic cascade exhibiting both positive and
      negative feedback loops. The predictions were tested for the key transcriptional
      regulator AUXIN RESPONSE FACTOR7 node, and over 70% of its targets were validated
      experimentally. Intriguingly, the predicted GRN revealed a mutual inhibition
      between the ARF7 and ARF5 modules that would control an early bifurcation between
      two cell fates. Analyses of the expression pattern of ARF7 and ARF5 targets
      suggest that this patterning mechanism controls flanking and central zone
      specification in Arabidopsis LR primordia. 

PMID- 25944106
TI  - High accuracy of ultrasound in diagnosing the presence and type of groin hernia.
AB  - BACKGROUND: To evaluate the accuracy of ultrasound (US) in diagnosing the the
      presence and type of groin hernia. METHODS: We retrospectively studied the
      results of 172 US examinations of the groin in 151 patients (101 men and 50
      women; mean age, 59 years) who had undergone US examination for suspected groin
      hernia. In total, 119 of the groin hernias had been diagnosed on US, and 108
      (91%) had required subsequent surgery. All patients who had had positive results
      for hernia on US and did not undergo surgery (n = 11) and most of the patients
      whose US results had been negative for hernia (n = 48) underwent limited MRI or
      CT scanning. We determined the sensitivity, specificity, and accuracy of US in
      diagnosing the presence and type of groin hernia. To identify any change in the
      accuracy of US over time at our institution, we compared the sensitivity,
      specificity, and accuracy of its use from January 2002 through December 2010 (n =
      54 groins) with those from January 2011 through December 2012 (n = 118 groins).
      RESULTS: The overall rates of sensitivity and specificity of US for diagnosing
      the presence of groin hernia were 96% and 96%. These rates reflect improvements
      from 92% and 88% prior to 2011 to 98% and 100% beginning in 2011. In addition,
      the overall accuracy of US for diagnosing the type of groin hernia was 96%. This
      also improved over time at our center from 91% prior to 2011 to 98% beginning in
      2011. CONCLUSIONS: US is highly accurate at diagnosing the presence and type of
      groin hernia.

PMID- 25944103
TI  - Indole Glucosinolate Biosynthesis Limits Phenylpropanoid Accumulation in
      Arabidopsis thaliana.
AB  - Plants produce an array of metabolites (including lignin monomers and soluble UV
      protective metabolites) from phenylalanine through the phenylpropanoid
      biosynthetic pathway. A subset of plants, including many related to Arabidopsis
      thaliana, synthesizes glucosinolates, nitrogen- and sulfur-containing secondary
      metabolites that serve as components of a plant defense system that deters
      herbivores and pathogens. Here, we report that the Arabidopsis thaliana reduced
      epidermal fluorescence5 (ref5-1) mutant, identified in a screen for plants with
      defects in soluble phenylpropanoid accumulation, has a missense mutation in
      CYP83B1 and displays defects in glucosinolate biosynthesis and in phenylpropanoid
      accumulation. CYP79B2 and CYP79B3 are responsible for the production of the
      CYP83B1 substrate indole-3-acetaldoxime (IAOx), and we found that the
      phenylpropanoid content of cyp79b2 cyp79b3 and ref5-1 cyp79b2 cyp79b3 plants is
      increased compared with the wild type. These data suggest that levels of IAOx or
      a subsequent metabolite negatively influence phenylpropanoid accumulation in ref5
      and more importantly that this crosstalk is relevant in the wild type. Additional
      biochemical and genetic evidence indicates that this inhibition impacts the early
      steps of the phenylpropanoid biosynthetic pathway and restoration of
      phenylpropanoid accumulation in a ref5-1 med5a/b triple mutant suggests that the
      function of the Mediator complex is required for the crosstalk. 

PMID- 25944107
TI  - Peritoneal fluid culture and antibiotic treatment in patients with perforated
      appendicitis in a Pacific Island.
AB  - BACKGROUND: Little data on the usefulness of microbiological samples in
      appendicular peritonitis (AP) are available. The objectives of the study were to
      document the clinical value of systematic peritoneal swabbing in complicated
      appendicitis, to establish whether they influence postoperative outcome, and to
      help to optimize empirical preoperative treatment. METHODS: Charts of all
      consecutive patients undergoing appendicectomy for acute perforated appendicitis
      were analyzed over a 7-year period from 2005 to 2011 in a tertiary hospital in
      New Caledonia. From prospectively recorded data, microbiological culture results,
      and sensitivity of isolates were obtained in relation to histopathological
      findings and infective morbidity. RESULTS: Overall, 144 cases including 47 (33%)
      children and 97 (67%) adults with perforated appendicitis were included in the
      study. Fifty-one (35%) had generalized peritonitis treated laparoscopically in 30
      (59%) cases. Peritoneal fluid samples yielded a positive culture in 104 (74%)
      patients. The most commonly recovered species were Escherichia coli (81%),
      Streptococcus milleri group (12%), and Pseudomonas aeruginosa (12%).
      Postoperative infectious complications occurred in 32 (22%) including intra
      abdominal abscess (n = 20) and wound infection (n = 12). Probabilist antibiotic
      regimen was less often suitable in children than in adults (p = 0.003).
      Infectious complications occurred more often in cases with an unsuitable
      antibiotic regimen after culture results compared with a suitable antibiotic
      regimen before culture results (p = 0.01). CONCLUSION: Although antibiotic use
      may be considered as an adjunct to surgical intervention of AP, the appropriate
      use of preoperative antibiotics and modifications according to culture results
      are essential to prevent infectious complications.

PMID- 25944108
TI  - Bilateral idiopathic granulomatous mastitis.
AB  - OBJECTIVES: Idiopathic granulomatous mastitis (IGM) is a benign rare inflammatory
      pseudotumor. Bilateral involvement of IGM has been reported in a few cases. To
      our knowledge, this study is the largest series of bilateral cases to date. The
      goals of this study were to present clinical features of bilateral IGM and to
      evaluate the results of treatments. MATERIALS AND METHODS: We performed a
      retrospective review of the idiopathic granulomatous mastitis database from 2010
      to 2013. Ten female patients who met required histologic and clinical criteria of
      IGM in both breasts were included in study. Demographic data, clinical findings,
      medication history, and radiologic findings are presented. RESULTS: The mean age
      at onset of the disease was 38.4 +/- 8.3 years (range: 29-52 years). Nine
      patients had no recurrence during a mean follow-up period of 21 months (range: 11
      26 months). Additionally, the median time to second breast involvement was 15.6
      months. CONCLUSION: Bilateral IGMs have a higher rate of more relapse and greater
      resistance to medical therapies than do unilateral IGMs. Surgical management
      should be avoided unless all medical treatment options have been exhausted.
      Nevertheless, expectant management seems a rational option for the treatment of
      bilateral IGM.

PMID- 25944110
TI  - Integration of lung cancer screening into practice is lacking.

PMID- 25944109
TI  - Neuropsychological profiles of an elderly cohort undergoing elective surgery and
      the relationship between cognitive performance and delirium.
AB  - OBJECTIVES: To examine baseline (preoperative) neuropsychological test
      performance in a cohort of elderly individuals undergoing elective surgery and
      the association between specific neuropsychological domains and postoperative
      delirium. DESIGN: Ongoing prospective cohort study. SETTING: Successful Aging
      after Elective Surgery Study. PARTICIPANTS: Elderly adults (N=300) scheduled for
      elective (noncardiac) surgery. MEASUREMENTS: Neuropsychological testing,
      including standardized assessments of memory, divided and sustained attention,
      speed of mental processing, verbal fluency, working memory, language, and an
      overall measure of premorbid cognitive functioning, was performed 2 to 4 weeks
      before surgery. The relationship between the individual neuropsychological tests
      and delirium status was examined using linear regression, adjusting for age, sex,
      and education. RESULTS: Study participants were generally highly educated (mean
      years of education 15.0+/-2.9), with minimal or no cognitive impairment (mean
      Modified Mini-Mental State Examination score 93.2 out of 100). After adjustment,
      participants who developed postoperative delirium had performed significantly
      lower preoperatively on measures of speed of mental processing and divided
      attention (Trail-Making Test Part B, mean difference 17.55, P=.02), category
      fluency (animal naming, mean difference -1.94, P=.01), sustained visual attention
      (Visual Search and Attention, mean difference -3.19, P<.001), and working memory
      with new learning and recall (Hopkins Verbal Learning Test-Revised Total mean
      difference -0.53 to -0.79, P<.01). CONCLUSION: Individuals who later develop
      delirium have lower scores on tests evaluating the areas of complex attention,
      executive functioning, and rapid access to verbal knowledge or semantic networks
      at baseline. Future studies to better understand how the cognitive profiles
      identified may predispose individuals to developing delirium may help pave the
      way to greater understanding of the mechanisms of delirium.

PMID- 25944112
TI  - On the proper selection of preictal period for seizure prediction.
AB  - Supervised machine learning-based seizure prediction methods consider preictal
      period as an important prerequisite parameter during training. However, the exact
      length of the preictal state is unclear and varies from seizure to seizure. We
      propose a novel statistical approach for proper selection of the preictal period,
      which can also be considered either as a measure of predictability of a seizure
      or as the prediction capability of an understudy feature. The optimal preictal
      periods (OPPs) obtained from the training samples can be used for building a more
      accurate classifier model. The proposed method uses amplitude distribution
      histograms of features extracted from electroencephalogram (EEG) recordings. To
      evaluate this method, we extract spectral power features in different frequency
      bands from monopolar and space-differential EEG signals of 18 patients suffering
      from pharmacoresistant epilepsy. Furthermore, comparisons among monopolar
      channels with space-differential channels, as well as intracranial EEG (iEEG) and
      surface EEG (sEEG) signals, indicate that while monopolar signals perform better
      in iEEG recordings, no significant difference is noticeable in sEEG recordings. 

PMID- 25944113
TI  - Generalized periodic discharges: Pathophysiology and clinical considerations.
AB  - Generalized periodic discharges (GPDs) are commonly encountered in metabolic
      encephalopathy and cerebral hypoxia/ischemia. The clinical significance of this
      EEG pattern is indistinct, and it is unclear whether treatment with antiepileptic
      drugs is beneficial. In this study, we discuss potential pathophysiological
      mechanisms. Based on the literature, supplemented with simulations in a minimal
      computational model, we conclude that selective synaptic failure or neuronal
      damage of inhibitory interneurons, leading to disinhibition of excitatory
      pyramidal cells, presumably plays a critical role. Reversibility probably depends
      on the potential for functional recovery of these interneurons. Whether
      antiepileptic drugs are helpful for regaining function is unclear. This article
      is part of a Special Issue entitled "Status Epilepticus". 

PMID- 25944111
TI  - Noncanonical regulation of alkylation damage resistance by the OTUD4
      deubiquitinase.
AB  - Repair of DNA alkylation damage is critical for genomic stability and involves
      multiple conserved enzymatic pathways. Alkylation damage resistance, which is
      critical in cancer chemotherapy, depends on the overexpression of alkylation
      repair proteins. However, the mechanisms responsible for this upregulation are
      unknown. Here, we show that an OTU domain deubiquitinase, OTUD4, is a positive
      regulator of ALKBH2 and ALKBH3, two DNA demethylases critical for alkylation
      repair. Remarkably, we find that OTUD4 catalytic activity is completely
      dispensable for this function. Rather, OTUD4 is a scaffold for USP7 and USP9X,
      two deubiquitinases that act directly on the AlkB proteins. Moreover, we show
      that loss of OTUD4, USP7, or USP9X in tumor cells makes them significantly more
      sensitive to alkylating agents. Taken together, this work reveals a novel,
      noncanonical mechanism by which an OTU family deubiquitinase regulates its
      substrates, and provides multiple new targets for alkylation chemotherapy
      sensitization of tumors. 

PMID- 25944114
TI  - Electrographic status epilepticus in children with critical illness: Epidemiology
      and outcome.
AB  - Electrographic seizures and electrographic status epilepticus are common in
      children with critical illness with acute encephalopathy, leading to increasing
      use of continuous EEG monitoring. Many children with electrographic status
      epilepticus have no associated clinical signs, so EEG monitoring is required for
      seizure identification. Further, there is increasing evidence that high seizure
      burdens, often classified as electrographic status epilepticus, are associated
      with worse outcomes. This review discusses the incidence of electrographic status
      epilepticus, risk factors for electrographic status epilepticus, and associations
      between electrographic status epilepticus and outcomes, and it summarizes recent
      guidelines and consensus statements addressing EEG monitoring in children with
      critical illness. This article is part of a Special Issue entitled "Status
      Epilepticus". 

PMID- 25944115
TI  - Reactive oxygen species generation by bovine blood neutrophils with different
      CXCR1 (IL8RA) genotype following Interleukin-8 incubation.
AB  - BACKGROUND: Associations between polymorphisms in the bovine CXCR1 gene, encoding
      the chemokine (C-X-C motif) receptor 1 (IL8RA), and neutrophil traits and
      mastitis have been described. In the present study, blood neutrophils were
      isolated from 20 early lactating heifers with different CXCR1 genotype at
      position 735 or 980. The cells were incubated with different concentrations of
      recombinant bovine IL-8 (rbIL-8) for 2 or 6 h and stimulated with phorbol 12
      myristate 13-acetate (PMA) or opsonized zymosan particles (OZP). Potential
      association between CXCR1 genotype and production of reactive oxygen species
      (ROS) was studied. RESULTS: Although on single nucleotide polymorphisms (SNPs)
      may potentially affect CXCR1 function, SNPs c.735C > G and c.980A > G showed no
      association with ROS production with or without incubation of rbIL-8. Neutrophils
      incubated with rbIL-8 for 2 or 6 h showed higher PMA- and lower OZP-induced ROS
      production compared to control without rbIL-8. CONCLUSIONS: In the present study
      no association could be detected between superoxide production by isolated bovine
      neutrophils during early lactation and CXCR1 gene polymorphism. IL-8 showed to
      possess inhibitory effects on ROS generation in bovine neutrophils.

PMID- 25944116
TI  - The antioxidant properties of organosulfur compounds (sulforaphane).
AB  - Sulforaphane (SFN) is a molecule within the isothiocyanate (ITC) group of
      organosulfur compounds. SFN is a phytochemical commonly found in cruciferous
      vegetables such as broccoli, brussels sprouts and cabbages. It has been widely
      studied in order to evaluate its chemopreventive properties and some of those
      have already been established by means of animal and human models. The SFN
      induces Phase I and II enzymes involved in detoxification processes of chemical
      carcinogens in order to prevent the start of carcinogenesis. It also presents
      anti-tumor action at post-initiation Phase, suggesting supplementary roles in
      cancer prevention. In a dose dependent manner, ITC inhibits the viability of
      human cancer cells, modifies epigenetic events that occur in cancer cells and
      present antiinflammatory effect acting during the initial of uncontrolled cell
      proliferation. This protective effect may be due to its antioxidant status, its
      recognized capacity to induce the expression and/or activity of of different
      cytoprotective proteins involved in the activating "Nuclear factor erythroid
      derived 2-like 2" (Nrf2). Nevertheless, the effects on health and the possible
      connections among different diet constituents in humans must be carefully studied
      as there are limitations in the current data in order to better understand the
      molecular mechanisms responsible for those effects. This survey also includes
      relevant patents on the use of SFN, like its use in skin cancer treatment
      (US2015038580); and as an adjuvant in anti-cancer treatment (US2014228419). The
      use of SFN as an antioxidant dietary supplement, methods for compositions that
      promote glutathione production (WO2015002279) and methods for extracting and
      purifying SFN from broccoli seeds (CN104086469) are also included in this review.

PMID- 25944117
TI  - Journey of water in pine cones.
AB  - Pine cones fold their scales when it rains to prevent seeds from short-distance
      dispersal. Given that the scales of pine cones consist of nothing but dead cells,
      this folding motion is evidently related to structural changes. In this study,
      the structural characteristics of pine cones are studied on micro-/macro-scale
      using various imaging instruments. Raindrops fall along the outer scales to the
      three layers (bract scales, fibers and innermost lignified structure) of inner
      pine cones. However, not all the layers but only the bract scales get wet and
      then, most raindrops move to the inner scales. These systems reduce the amount of
      water used and minimize the time spent on structural changes. The result shows
      that the pine cones have structural advantages that could influence the efficient
      motion of pine cones. This study provides new insights to understand the motion
      of pine cones and would be used to design a novel water transport system. 

PMID- 25944119
TI  - Diagnosis and treatment for obstructive sleep apnea: Fundamental and clinical
      knowledge in obstructive sleep apnea.
AB  - PURPOSE: This review article covers the diagnosis and treatment of obstructive
      sleep apnea (OSA) from a dental perspective. It addresses the issue of when and
      how to screen for and then, if indicated, refer the patient for a more
      comprehensive. STUDY SELECTION: Our focus in this article was on identifying
      current unanswered questions that relevant to OSA problems that dental scientists
      have to pursue and on providing valuable information on that problems,
      consequently the previous studies which investigated or reviewed the diagnosis
      and treatment of OSA were included. In addition, we included studies on jaw
      movements during sleep and on the use of a lateral cephalometric film related to
      the diagnosis and treatment of OSA. RESULTS: The role of portable sleep
      monitoring devices versus full laboratory polysomnography is discussed. This
      review also describes what is known about the efficacy of mandibular advancement
      devices and when and how they fit in to a treatment program for a patient with
      obstructive sleep apnea. Finally some basic research is presented on jaw
      movements during sleep and how a lateral cephalometric film can be used to assess
      the changes of the airway with body posture and head posture. CONCLUSION: This
      article provides the valuable suggestions for the clinical questions in the
      diagnosis and treatment of OSA.

PMID- 25944122
TI  - Doctor should be able to help dying man commit suicide, rules South African
      judge.

PMID- 25944120
TI  - Mutual reinforcement of inflammation and carcinogenesis by the Helicobacter
      pylori CagA oncoprotein.
AB  - Helicobacter pylori cagA-positive strain delivers the CagA oncoprotein into
      gastric epithelial cells and at the same time elicits stomach inflammation. To
      experimentally investigate the pathophysiological interplay between CagA and
      inflammation, transgenic mice systemically expressing the bacterial cagA gene
      were treated with a colitis inducer, dextran sulfate sodium (DSS). Compared with
      control mice, DSS-induced colitis was markedly deteriorated in cagA-transgenic
      mice. In the colonic epithelia of cagA-transgenic mice, there was a substantial
      decrease in the level of IkappaB, which binds and sequesters NF-kappaB in the
      cytoplasm. This IkappaB reduction was due to CagA-mediated inhibition of PAR1,
      which may stimulate IkappaB degradation by perturbing microtubule stability.
      Whereas the CagA-mediated IkappaB reduction did not automatically activate NF
      kappaB, it lowered the threshold of NF-kappaB activation by inflammogenic
      insults, thereby contributing to colitis exacerbation in cagA-transgenic mice.
      CagA also activates inflammasomes independently of NF-kappaB signaling, which
      further potentiates inflammation. The incidence of colonic dysplasia was elevated
      in DSS-treated cagA-transgenic mice due to a robust increase in the number of pre
      cancerous flat-type dysplasias. Thus, CagA deteriorated inflammation, whereas
      inflammation strengthened the oncogenic potential of CagA. This work revealed
      that H. pylori CagA and inflammation reinforce each other in creating a downward
      spiral that instigates neoplastic transformation. 

PMID- 25944124
TI  - Gambling in Singapore: an overview of history, research, treatment and policy.
AB  - AIMS: This paper describes the current situation regarding gambling in Singapore
      in relation to its historical and cultural context. METHODS: A computerized
      search was performed of two databases (PubMed and PsychINFO) and the reference
      lists from the papers searched manually to identify relevant studies. The
      findings were synthesized and their implications assessed. RESULTS: In addition
      to state lotteries and much informal gambling, Singapore has two large resort
      casinos, which rank third after Las Vegas and Macau in terms of gross revenues.
      The major ethnic subgroups in Singapore have different cultural connections to
      gambling, including the active involvement of the Chinese and religious
      prohibition among the Malay. A range of secondary prevention and treatment
      services has been developed to attempt to minimize potential negative impacts.
      Overall, the prevalence of pathological gambling and problem gambling has
      decreased in recent years: an estimated 0.2% are classified as probable
      pathological gamblers compared with 1.4% in 2011, 1.2% in 2008 and 2.1% in 2005.
      CONCLUSIONS: Singapore has experienced a reduction in problem gambling prevalence
      which may reflect the influence of multiple initiatives.

PMID- 25944123
TI  - Chromosomal instability as a prognostic marker in cervical cancer.
AB  - BACKGROUND: Cervical cancer is the third most common cancer in women globally,
      and despite treatment, distant metastasis and nodal recurrence will still develop
      in approximately 30% of patients. The ability to predict which patients are
      likely to experience distant relapse would allow clinicians to better tailor
      treatment. Previous studies have investigated the role of chromosomal instability
      (CIN) in cancer, which can promote tumour initiation and growth; a hallmark of
      human malignancies. In this study, we sought to examine the published CIN70 gene
      signature in a cohort of cervical cancer patients treated at the Princess
      Margaret (PM) Cancer Centre and an independent cohort of The Cancer Genome Atlas
      (TCGA) cervical cancer patients, to determine if this CIN signature associated
      with patient outcome. METHODS: Cervical cancer samples were collected from 79
      patients, treated between 2000-2007 at the PM, prior to undergoing curative chemo
      radiation. Total RNA was extracted from each patient sample and analyzed using
      the GeneChip Human Genome U133 Plus 2.0 array (Affymetrix). RESULTS: High CIN70
      scores were significantly related to increased chromosomal alterations in TCGA
      cervical cancer patients, including a higher percentage of genome altered and a
      higher number of copy number alterations. In addition, this same CIN70 signature
      was shown to be predictive of para-aortic nodal relapse in the PM Cancer Centre
      cohort. CONCLUSIONS: These findings demonstrate that chromosomal instability
      plays an important role in cervical cancer, and is significantly associated with
      patient outcome. For the first time, this CIN70 gene signature provided
      prognostic value for patients with cervical cancer.

PMID- 25944125
TI  - Rheological characterization of an injectable alginate gel system.
AB  - BACKGROUND: This work investigates a general method for producing alginate gel
      matrices using an internal mode of gelation that depends solely on soluble
      alginate and alginate/gelling ion particles. The method involves the formulation
      of two-component kits comprised of soluble alginate and insoluble
      alginate/gelling ion particles. Gelling kinetics, elastic and Young's moduli were
      investigated for selected parameters with regard to soluble alginate guluronate
      content, molecular weight, calcium or strontium gelling ions and alginate gelling
      ion particle sizes in the range between 25 and 125 micrometers. RESULTS: By
      mixing the two components and varying the parameters mentioned above, alginate
      gel matrices with tailor-made viscoelastic properties and gelling kinetics were
      obtained. Final gel elasticity depended on alginate type, concentration and
      gelling ion. The gelling rate could be manipulated, e.g. through selection of the
      alginate type and molecular weight, particle sizes and the concentration of non
      gelling ions. CONCLUSIONS: Formulations of the injectable and moldable alginate
      system presented have recently been used within specific medical applications and
      may have potential within regenerative medicine or other fields.

PMID- 25944126
TI  - Formulation and evaluation of tacrolimus-loaded galactosylated Poly(lactic-co
      glycolic acid) nanoparticles for liver targeting.
AB  - OBJECTIVE: The aim of this investigation was to formulate liver targeted
      tacrolimus-loaded nanoparticles for reducing renal distribution and thereby
      decreasing nephrotoxicity. METHOD: Poly lactic-co-glycolic acid (PLGA) was
      galactosylated, and confirmation of galactosylation was performed by Fourier
      transform infrared spectroscopy and nuclear magnetic resonance spectroscopy.
      Tacrolimus-loaded PLGA nanoparticles (Tac-PLGA NP) and galactosylated PLGA
      nanoparticles (Tac-Gal-PLGA NPs) were prepared by ultrasonic emulsification
      solvent evaporation technique and characterized. KEY FINDINGS: The size of both
      the formulations was below 150 nm and negative zeta potential indicated the
      stability and reticuloendothelial system targeting efficiency. The in-vitro
      release and pharmacokinetics showed sustained release of tacrolimus from
      nanoparticles in comparison to plain drug solution. The biodistribution studies
      revealed the potential of both the nanoparticulate systems to target tacrolimus
      to the liver for prolonged periods of time compared with the plain drug solution.
      However, significantly higher liver and spleen targeting efficiency of Tac-Gal
      PLGA NPs compared with Tac-PLGA NPs was evident indicating its active targeting.
      Significantly lower distribution in the kidney from nanoparticles indicated the
      possibility of reduced nephrotoxicity - the principal reason for patient non
      compliance. Both nanoparticles showed stability at refrigerated condition (5
      degrees C +/- 3 degrees C) upon storage for 1 month. CONCLUSION: Galactosylated
      PLGA nanoparticles seem to be a promising carrier for liver targeting of
      tacrolimus.

PMID- 25944127
TI  - Products for the treatment of inflammatory bowel disease: a patent review (2013 -
      2014).
AB  - INTRODUCTION: Inflammatory bowel disease (IBD) consists of Crohn's disease,
      ulcerative colitis and an unspecific IBD. The unclear etiology of IBD is a
      limiting factor that complicates the development of new pharmacological
      treatments and explains the high frequency of refractory patients to current
      drugs, including both conventional and biological therapies. In view of this,
      recent progress on the development of novel patented products to treat IBD was
      reviewed. AREAS COVERED: Evaluation of the patent literature during the period
      2013 - 2014 focused on chemical compounds, functional foods and biological
      therapy useful for the treatment of IBD. EXPERT OPINION: Majority of the patents
      are not conclusive because they were based on data from unspecific methods not
      related to intestinal inflammation and, when related to IBD models, few
      biochemical and molecular evaluations that could be corroborating their use in
      human IBD were presented. On the other hand, methods and strategies using new
      formulations of conventional drugs, guanylyl cyclase C peptide agonists,
      compounds that influence anti-adhesion molecules, mAbs anti-type I interferons
      and anti-integrin, oligonucleotide antisense Smad7, growth factor neuregulin 4
      and functional foods, particularly fermented wheat germ with Saccharomyces
      cerevisiae, are promising products for use in the very near future.

PMID- 25944128
TI  - Holter monitoring to detect silent atrial fibrillation in high-risk subjects: the
      Perugia General Practitioner Study.
AB  - Atrial fibrillation (AF) is diagnosed for the first time in about 5 % of patients
      admitted for acute ischemic stroke. Advanced aged and arterial hypertension are
      risk factors for AF. We evaluated the prevalence of silent AF in subjects with
      advanced age and systemic arterial hypertension. Subjects of both gender, aged 65
      years or more with systemic arterial hypertension were randomly identified from
      the patient lists of the participating general practitioners in the Perugia area,
      in Italy. Study subjects underwent baseline 12-lead ECG and, if this did not show
      AF, 48-h Holter monitoring was performed. AF was known and confirmed by 12-lead
      ECG in 4 out of the 308 evaluated subjects (1.3 %). Baseline 12-lead ECG showed
      no cases of silent AF. Holter monitoring was performed in 300 subjects, mean age
      70 +/- 4. Twenty-six recordings were not evaluable for the presence of artifacts;
      therefore, 274 subjects were included in the analysis. Holter monitoring showed
      AF in 27 out of 274 subjects (10 %; 95 % confidence interval 6.4-13.5 %); AF was
      longer than 30 s in four of the subjects. In 56 additional subjects, Holter
      monitoring revealed excessive supraventricular ectopic activity (20 %; 95 %
      confidence interval 15.3-24.7 %). Holter monitoring was able to detect silent AF
      in about 10 % of subjects aged 65 or above with systemic arterial hypertension.
      The risk of stroke associated with screened silent AF should be carefully
      evaluated.

PMID- 25944129
TI  - Dual antiplatelet therapy tailored on platelet function test after coronary stent
      implantation: a real-world experience.
AB  - Patients' response to dual antiplatelet therapy (DAPT) is subject to variations
      and its monitoring allows to individualize this therapy. In this study, we
      evaluated if a strategy of tailored DAPT after platelet function testing could
      reduce high on-treatment platelet reactivity (HPR) and improve outcome of
      patients treated with stent implantation. In 257 patients undergoing percutaneous
      angioplasty, platelet function was measured by light transmittance aggregometry
      (LTA) using 10 uM/L adenosine-diphosphate (ADP) and 1 mM arachidonic acid (AA) as
      agonists. Patients with HPR by ADP (>=70%) were switched to double-dose
      clopidogrel, ticlopidine, prasugrel or ticagrelor; in patients with HPR by AA
      (>=20%) acetylsalicylic acid dose was increased if not contraindicated. Platelet
      function analysis was repeated 48 hours after therapy variation. At 20-month
      follow-up major adverse cardiovascular events (MACE) and bleedings were assessed.
      HPR was detected in 97/257 (37.7%) patients: 69/257 (26.8%) had HPR by ADP and
      71/257 (27.6%) had HPR by AA. In patients with HPR by ADP or by AA, tailored DAPT
      determined a significant reduction in residual platelet reactivity. No
      significant difference in MACE or bleeding occurrence was documented in HPR
      patients treated with tailored DAPT vs. those without HPR. HPR patients treated
      with tailored DAPT had significant lower follow-up MACE and deaths vs. 139 HPR
      patients not switched, even after propensity score analysis. These results
      suggest that a DAPT tailored on platelet testing can improve antiplatelet
      response in HPR patients, possibly reducing their thrombotic events to a level
      similar to non-HPR patients, without increasing the risk of bleeding.

PMID- 25944131
TI  - An update on the pathophysiology of idiopathic intracranial hypertension alias
      pseudotumor cerebri.
AB  - Idiopathic intracranial hypertension (IIH) is a syndrome characterized by
      increased intracranial pressure of unknown cause, leading to severe headache,
      papilledema and visual disturbances. Its former name, pseudotumor cerebri, has
      gained popularity recently. The strongest and most consistent risk factors of IIH
      are obesity and female gender. Infrequently, IIH may present in the absence of
      papilledema showing a headache profile similar to chronic daily headache with
      migrainous features. There have been several proposed mechanisms to explain the
      etiology of this disorder associated with various clinical conditions. In recent
      years, some inflammatory factors, natriuretic peptides and aquaporins have been
      proposed as possible contributors of the pathogenesis. On the other hand, some
      investigators have reported that bilateral transverse sinus stenosis is seen in
      the majority of IIH patients; therefore, dural sinus stent placement is used in
      some patients. No single theory has been able to provide a comprehensive answer,
      and there is no consensus about the exact cause of IIH. The aim of this review
      was to discuss the new insights on the mysterious pathogenesis of IIH.

PMID- 25944130
TI  - Diagnostic value of neutrophil gelatinase-associated lipocalin, cystatin C, and
      soluble triggering receptor expressed on myeloid cells-1 in critically ill
      patients with sepsis-associated acute kidney injury.
AB  - INTRODUCTION: Neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (Cys
      C), and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) are
      novel diagnostic biomarkers of acute kidney injury (AKI). We aimed to determine
      the diagnostic properties of these biomarkers for detecting AKI in critically ill
      patients with sepsis. METHODS: We divided 112 patients with sepsis into non-AKI
      sepsis (n = 57) and AKI sepsis (n = 55) groups. Plasma and urine specimens were
      collected on admission and every 24 hours until 72 hours and tested for NGAL, Cys
      C, and TREM-1 concentrations. Their levels were compared on admission, at
      diagnosis, and 24 hours before diagnosis. RESULTS: Both plasma and urine NGAL,
      Cys-C, and sTREM-1 were significantly associated with AKI development in patients
      with sepsis, even after adjustment for confounders by using generalized
      estimating equations. Compared with the non-AKI sepsis group, the sepsis AKI
      group exhibited markedly higher levels of these biomarkers at diagnosis and 24
      hours before AKI diagnosis (P < 0.01). The diagnostic and predictive values of
      plasma and urine NGAL were good, and those of plasma and urine Cys-C and sTREM-1
      were fair. CONCLUSION: Plasma and urine NGAL, Cys-C, and sTREM-1 can be used as
      diagnostic and predictive biomarkers for AKI in critically ill patients with
      sepsis.

PMID- 25944132
TI  - Relationship between restless leg syndrome and quality of life in uremic
      patients.
AB  - OBJECTIVES: Patients with RLS suffer nonrestorative sleep, daytime sleepiness,
      fatigue, and concentration problems. In addition, dialysis itself effects the
      psychological and social life of the patient negatively. The aim of this study
      was to determine the prevalence of RLS in patients on regular hemodialysis, and
      its relationship with patients' quality of life, socio-demographic and laboratory
      data. METHODS: One hundred and eighteen stable chronic hemodialysis (HD) patients
      referring to the hemodialysis unit of Turkish Kidney Foundation and 49 patients
      that met IRLSSG diagnostic criteria were included into the study. IRLSSG
      Diagnostic Criteria and International Restless Leg Syndrome rating scale were
      used as a guideline to diagnose and evaluate the severity of RLS. Short form-36
      health survey was used to evaluate the quality of life. For statistical analysis,
      the "SPSS for Windows" package program was used. RESULTS: A total of forty-nine
      patients, of whom 26 were female and 23 were male, that met IRLSSG diagnostic
      criteria were included into the study. Mean age of the patients was 61.35 +/-
      13.17 years. There was a negative correlation between the IRLSS score and SF36
      Physical Score, Mental Score and Total Score, respectively (p=0.018 r=-0.351,
      p=0.01 r=-0.380, p=0.00 r=-0.499). There was no significant correlation between
      the IRLSS score and dialysis duration, blood ferritin and parathyroid hormone and
      other comorbid diseases. CONCLUSION: RLS is a common distressing problem in
      patients with ESRD, which negatively impacts functional health status. Clinicians
      should be aware of the symptoms of RLS to decrease morbidities related with
      quality of life.

PMID- 25944133
TI  - Pain levels of examined muscles and gender differences in pain during
      electromyography.
AB  - OBJECTIVES: The aim of this study was to evaluate the pain level of each muscle
      during an EMG study and also search for any association between the pain levels
      and gender. METHODS: Two hundred and twenty-seven subjects (166 females and 111
      males) participated in the present study. Numeric analogue scale (NAS) was
      obtained from the patients after needle EMG for each muscle. RESULTS: In total,
      1242 muscles were examined. The highest pain levels among examined muscles were
      found on Abductor Pollicis Brevis (APB) (5.8 +/- 2.6), First Dorsal Interosseous
      (4.2 +/- 2.6) and Vastus Lateralis (4.0 +/- 2.6). NAS levels of the female
      patients (4.3 +/- 2.7) were apparently higher than those of the male patients
      (2.8 +/- 2.3) (p<0.01). CONCLUSION: First Dorsal Interosseous muscle was found
      less painful than APB muscle for the patients. Our study displayed greater pain
      sensitivity among females compared with males during the needle EMG; however, the
      pain levels of examined muscles were not higher than moderate for both genders.

PMID- 25944134
TI  - Effect of transforaminal anterior epidural steroid injection on neuropathic pain,
      quality of sleep and life.
AB  - OBJECTIVES: Transforaminal anterior steroid injections are frequently used for
      low back pain. In the current study, It was aimed to investigate the effects of
      transforaminal anterior epidural steroid injection (TAESI) in patients with low
      back pain in regards to quality of life and sleep, and neuropathic pain. METHODS:
      Ethics committee approval and patient consent were obtained. Patients with low
      back pain scheduled to receive transforaminal epidural steroid injections between
      October 2011 and October 2012 were included into the study. Pittsburgh Sleep
      Quality Index (PSQI), Short form 12 (SF 12), DN4 tests and Visual Analog Scale
      Score (VAS) were measured prior to procedure and three months later. All the
      tests were compared with baseline evaluations prior to injections. RESULTS: One
      hundred and two (female/male: 52/50) patients with a mean age of 53.3 +/- 1.4
      were included. Primary diagnoses were lumbar disc herniation in eighty-seven
      patients, spinal stenosis in seven and failed back surgery syndrome in eight
      patients. Statistically significant improvement was seen in the total VAS, DN4
      and PSQI scores (p=0.0001) of the patients at the third month follow-up. Sleep
      duration (p=0.0001), habitual sleep efficiency (p=0.0001), subjective sleep
      quality (p=0.003), sleep latency (p=0.014), sleep disturbances (p<0.001), sleep
      medication use (p=0.003), and day time dysfunction (p=0.015) showed a significant
      decrease in sub-components. There was no significant difference in SF 12 quality
      of life. CONCLUSION: It was determined in the study that transforaminal epidural
      steroid injection provided a substantial improvement in patients' pain and
      neuropathic pain and quality of sleep, but had no effect on the quality of life.

PMID- 25944135
TI  - The relation between pain perceived by the patients hospitalized in the algology
      clinic and their sleep and quality of life.
AB  - OBJECTIVES: The aim of the present study was to determine the effects of
      perceived pain on quality of sleep and life in patients hospitalized in a pain
      clinic. METHODS: Population of the present descriptive study composed of patients
      (>18 years old) treated as inpatients in the algology clinic of a university
      located at the city center of Sivas, who consented to participate in the study
      (122 patients). Data were collected through Personal Information Form, Visual
      Analog Scale (VAS), Pittsburg Sleep Quality Index (PSQI) and Short Form 36. Data
      were analyzed using independent t-test, Mann Whitney U test, Kruskal Wallis test
      and Pearson correlation test. Statistical significance level was set at p<0.05.
      RESULTS: A moderate negative correlation was found between VAS and three
      dimensions of SF-36, namely Physical Functioning, Role-Physical and Role
      Emotional. VAS was weakly and negatively correlated to Vitality and Mental
      Health. There was a good linear correlation between VAS and quality of life
      (QoL), pain score while there was a moderate linear correlation between VAS and
      the total sleep score. It was found that quality of life was not statistically
      significantly correlated to General Health and Social Functioning. CONCLUSION:
      There is a relationship between pain, sleep quality and quality of life. Quality
      of sleep and life was found to decrease as the level of pain increased, and
      quality of life was affected negatively when the quality of sleep was poor.
      Applications towards resolving pain would have a positive effect on the quality
      of sleep and life.

PMID- 25944136
TI  - [Incidence of chronic pain after ingunial hernia repair].
AB  - OBJECTIVES: The percentage of chronic pain in adults having inguinal hernia
      repair is 5-35%. Although this pain is thought to be related to some reasons,
      there is not an exact conclusion about this. In this study, the aim was to point
      out the incidence of chronic pain after inguinal hernia repair and determination
      of the risk factors. METHODS: Two hundred and four patients having inguinal
      hernia surgery between January 2011 and December 2012 were included into this
      study. The patients' pain was measured with VAS within 24 hours and at the third
      and the sixth month after surgery. The patients whose VAS was >3 three months
      after surgery were evaluated to have chronic pain. RESULTS: The incidence of pain
      continuing 3 months after surgery was 18.6% and 11.2% six months after surgery.
      78.3% of the patients had already had pain before surgery, and in 28% of them,
      chronic pain had evolved. The measure of VAS within 24 hours postoperatively was
      found higher in patients who developed chronic pain (3.13 +/- 1.12/1.71 +/-
      1.27). 5.2% of the patients had re-operation for reparation and chronic pain
      developed in all. Chronic pain was neuropathic in 48% of the patients, and its
      severity was moderate. CONCLUSION: The incidence of chronic pain after inguinal
      hernia repair was found %18, compatible with similar studies. Compared with other
      risk factors, preoperative pain, postoperative severe acute pain and reoperations
      were thought to be the most important risk factors for the development of chronic
      pain.

PMID- 25944137
TI  - [Symptoms seen in inpatient palliative care and impact of palliative care unit on
      symptom control].
AB  - OBJECTIVES: The purpose of this study was to determine the symptoms observed
      during admission to palliative care in patients that would be provided palliative
      support, to measure their intensity, and to evaluate the effect of palliative
      care on patient symptoms by recording changes during the first week after
      admission to hospital. METHODS: The sample of the study was determined as 108
      according to the population mean significance test conducted by using preliminary
      application data. Patients who were able to complete the Edmonton Symptom
      Assessment Scale during admission to hospital, on the 3(rd) and 7(th) days of
      hospitalization were included into the evaluation. The Introductory
      Characteristics Questionnaire, Edmonton Symptom Assessment Scale and Palliative
      Performance Scale were used for the collection of the data. RESULTS: While 50% of
      the patients defined pain intensity as 5 and over during admission, this rate was
      determined to be 6.5% on the 7(th) day. Mean values of the symptoms of pain,
      insomnia, loss of appetite, and status of well-being decreased significantly on
      the 3(rd) and 7(th) days after admission compared to the time of admission to the
      hospital. Besides, no statistically significant difference was found among the
      symptoms of nausea, anxiety, shortness of breath, and constipation. CONCLUSION:
      In this study, it was determined that the intensity of symptoms deteriorating the
      life quality of cancer patients such as pain, fatigue, insomnia, loss of
      appetite, and status of well-being improved rapidly with palliative care support.

PMID- 25944138
TI  - [Sporadic hemiplegic migraine].
AB  - Hemiplegic migraine, whose etiology is unclear, is a specific form of migraine
      with aura including hemiparesis. In this study, it was aimed to present the case
      of a 39-year-old women, suffering from sporadic hemiplegic migraine. The patient
      suffered recurrent severe headaches, and existing focal neurological symptoms,
      including alternant hemiparesis. On the basis of the history, thorough clinical
      observation and numerous accessory investigations, a diagnosis of sporadic
      hemiplegic migraine was established. Differential diagnoses of SHM were
      highlighted. 

PMID- 25944139
TI  - [Post-stroke complicated pain].
AB  - A seventy-seven year-old male patient had a stroke two years ago. Following the
      stroke, the patient had continuous, excruciating, severe pain between the left
      knee, which increased when standing and walking. We looked into the change in the
      character of the patient's pain after treatment. This study aimed to present our
      treatment approaches to the patients who develop central neuropathic pain,
      degenerative disk disease-related peripheral neuropathic pain and radicular
      nociceptive pain, and gonarthrosis-related nociceptive pain in the left leg
      following stroke. 

PMID- 25944140
TI  - [Secondary cluster headache due to cavernous sinus meningioma].

PMID- 25944141
TI  - Folliculitis following greater occipital nerve block.

PMID- 25944142
TI  - Straight to flexible sigmoidoscopy: rationalization of 2-week wait referrals in
      suspected colorectal cancer.
AB  - AIM: The 2-week wait pathway was designed to decrease the time from presentation
      to primary care of patients with 'red flag' symptoms of suspected cancer for
      review by a specialist for the diagnosis or exclusion of cancer. In our tertiary
      referral centre we have found that 968 colonoscopies per year are required to
      satisfy the demand for the 2-week wait, leading to limited colonoscopy
      availability for other services. We sought to determine the yield of colorectal
      cancer found at colonoscopy referred via the 2-week wait and referenced to the
      original red flag symptoms. This was in order to select the most efficacious
      alternative primary investigation based upon presenting symptoms. METHOD:
      Electronic records were retrospectively analysed. All patients who went through
      the 2-week wait for suspicion of colorectal cancer in 2013 and were found to have
      colorectal cancer on colonoscopy were included. Patients not undergoing
      colonoscopy as the first investigation were excluded. The splenic flexure was
      deemed to be within the range of a flexible sigmoidoscope. RESULTS: In all, 2950
      referrals were made. 968 colonoscopies were performed as the primary
      investigation of which 35 were found to have colorectal cancer. No patients
      referred with rectal bleeding and another symptom had a tumour more proximal to
      the range of flexible sigmoidoscopy. 80% of tumours proximal to the splenic
      flexure were suitable for CT diagnosis alone. CONCLUSION: Our data support the
      use of flexible sigmoidoscopy alone as an initial investigation for patients
      presenting with rectal bleeding with or without additional colorectal symptoms.
      Patients with anaemia (without bleeding) or change in bowel habit (without
      bleeding) may be investigated with CT colonography alone; colonoscopy may then be
      used selectively prior to surgery.

PMID- 25944143
TI  - Comparative characteristics of the VP7 and VP4 antigenic epitopes of the
      rotaviruses circulating in Russia (Nizhny Novgorod) and the Rotarix and RotaTeq
      vaccines.
AB  - Two live, attenuated rotavirus A (RVA) vaccines, Rotarix and RotaTeq, have been
      successfully introduced into national immunization programs worldwide. The parent
      strains of both vaccines were obtained more than 30 years ago. Nonetheless, only
      very limited data are available on the molecular similarity of the vaccine
      strains and their genetic relationships to the wild-type strains circulating
      within the territory of Russian Federation. In this study, we have determined the
      nucleotide sequences of the genes encoding the viral proteins VP7 and VP4 (the
      globular domain VP8*) of vaccine strains and natural isolates of rotaviruses in
      Nizhny Novgorod, Russia. The VP7 and VP4 proteins contain antigenic sites that
      are the main targets of neutralizing antibodies. Phylogenetic analysis based on
      VP4 and VP7 showed that the majority of the natural RVA isolates from Nizhny
      Novgorod and the vaccine strains belong to different clusters. Four amino acids
      within the VP7 antigenic sites were common in both the wild-type and vaccine
      strains. The largest number of amino acid differences was found between the
      vaccine strain Rotarix and the Nizhny Novgorod G2 strains (19 residues out of
      29). From 3 to 5 amino acid differences per strain were identified in the
      antigenic sites of VP4 (domain VP8*) between wild-type strains and the vaccine
      RotaTeq, and 6-8 substitutions were found when they were compared with the
      vaccine strain Rotarix. For the first time, immunodominant T-cell epitopes of VP7
      were analyzed, and differences in the sequences between the vaccine and the wild
      type strains were found. The accumulation of amino acid substitutions in the VP7
      and VP4 antigenic sites may potentially reduce the immune protection of
      vaccinated children from wild-type strains of rotavirus. 

PMID- 25944144
TI  - Unusual peripapillary new vessels in eye with central serous chorioretinopathy.

PMID- 25944146
TI  - Percutaneous Facet Screw Fixation in the Treatment of Symptomatic Recurrent
      Lumbar Facet Joint Cyst: A New Technique.
AB  - We present a case of percutaneous treatment of symptomatic recurrent lumbar facet
      joint cyst resistant to all medical treatments including facet joint steroid
      injection. Percutaneous transfacet fixation was then performed at L4-L5 level
      with a cannulated screw using CT and fluoroscopy guidance. The procedure time was
      30 min. Using the visual analog scale (VAS), pain decreased from 9.5,
      preoperatively, to 0 after the procedure. At 6-month follow-up, an asymptomatic
      cystic recurrence was observed, which further reduced at the 1-year follow-up.
      Pain remained stable (VAS at 0) during all follow-ups. CT- and fluoroscopy-guided
      percutaneous cyst rupture associated with facet screw fixation could be an
      alternative to surgery in patients suffering from a symptomatic recurrent lumbar
      facet joint cyst.

PMID- 25944145
TI  - Cardiac effects of seasonal ambient particulate matter and ozone co-exposure in
      rats.
AB  - BACKGROUND: The potential for seasonal differences in the physicochemical
      characteristics of ambient particulate matter (PM) to modify interactive effects
      with gaseous pollutants has not been thoroughly examined. The purpose of this
      study was to compare cardiac responses in conscious hypertensive rats co-exposed
      to concentrated ambient particulates (CAPs) and ozone (O3) in Durham, NC during
      the summer and winter, and to analyze responses based on particle mass and
      chemistry. METHODS: Rats were exposed once for 4 hrs by whole-body inhalation to
      fine CAPs alone (target concentration: 150 MUg/m3), O3 (0.2 ppm) alone, CAPs plus
      O3, or filtered air during summer 2011 and winter 2012. Telemetered
      electrocardiographic (ECG) data from implanted biosensors were analyzed for heart
      rate (HR), ECG parameters, heart rate variability (HRV), and spontaneous
      arrhythmia. The sensitivity to triggering of arrhythmia was measured in a
      separate cohort one day after exposure using intravenously administered
      aconitine. PM elemental composition and organic and elemental carbon fractions
      were analyzed by high-resolution inductively coupled plasma-mass spectrometry and
      thermo-optical pyrolytic vaporization, respectively. Particulate sources were
      inferred from elemental analysis using a chemical mass balance model. RESULTS:
      Seasonal differences in CAPs composition were most evident in particle mass
      concentrations (summer, 171 MUg/m3; winter, 85 MUg/m3), size (summer, 324 nm;
      winter, 125 nm), organic:elemental carbon ratios (summer, 16.6; winter, 9.7), and
      sulfate levels (summer, 49.1 MUg/m3; winter, 16.8 MUg/m3). Enrichment of metals
      in winter PM resulted in equivalent summer and winter metal exposure
      concentrations. Source apportionment analysis showed enrichment for anthropogenic
      and marine salt sources during winter exposures compared to summer exposures,
      although only 4% of the total PM mass was attributed to marine salt sources.
      Single pollutant cardiovascular effects with CAPs and O3 were present during both
      summer and winter exposures, with evidence for unique effects of co-exposures and
      associated changes in autonomic tone. CONCLUSIONS: These findings provide
      evidence for a pronounced effect of season on PM mass, size, composition, and
      contributing sources, and exposure-induced cardiovascular responses. Although
      there was inconsistency in biological responses, some cardiovascular responses
      were evident only in the co-exposure group during both seasons despite
      variability in PM physicochemical composition. These findings suggest that a
      single ambient PM metric alone is not sufficient to predict potential for
      interactive health effects with other air pollutants.

PMID- 25944147
TI  - Renal Sympathetic Denervation by CT-scan-Guided Periarterial Ethanol Injection in
      Sheep.
AB  - BACKGROUND: Renal nerves are a recent target in the treatment of hypertension.
      Renal sympathetic denervation (RSD) is currently performed using catheter-based
      radiofrequency ablation (RFA) and because this method has limitations,
      percutaneous magnetic resonance (MR)-guided periarterial ethanol injection is a
      suggested alternative. However, few studies have been conducted on the
      effectiveness of percutaneous ethanol injection for RSD. AIM: To evaluate the
      feasibility, efficacy, and complications of computed tomography (CT)-guided
      periarterial ethanol injection. METHODS: Ethanol (10 ml, 99.6%) was injected
      around the right renal artery in six sheep under CT guidance with the left kidney
      serving as a control. Before and after the intervention, the sheep underwent MR
      imaging studies and the serum creatinine level was measured. One month after the
      intervention, the sheep were euthanized and norepinephrine (NE) concentration in
      the renal parenchyma was measured to evaluate the efficacy of the procedure. The
      treated tissues were also examined histopathologically to evaluate vascular,
      parenchymal, and neural injury. RESULTS: The right kidney parenchymal NE
      concentration decreased significantly compared with the left kidney after
      intervention (average reduction: 40%, P = 0.0016). Histologic examination
      revealed apparent denervation with no other vascular or parenchymal injuries
      observed in the histological and imaging studies. CONCLUSION: Effective and
      feasible RSD was achieved using CT-guided periarterial ethanol injection. This
      technique may be a potential alternative to catheter-based RFA in the treatment
      of hypertension.

PMID- 25944148
TI  - Digestive Tract Complications of Renal Cryoablation.
AB  - We report a case each of duodenorenal and colorenal fistula that arose after
      computed tomography-guided percutaneous cryoablation (PCA) for renal cell
      carcinoma and use imaging and endoscopic findings to analyze their causes and
      mechanisms. Both complications occurred though the edge of the iceball did not
      touch the intestinal wall, and patients' symptoms and fistula formation occurred
      several days after the PCA procedure. Based on imaging and endoscopy findings, we
      suspected the colorenal fistula resulted from bowel injury caused by ischemia
      from the occlusion of small vessels at the procedure's low temperature. Both
      cases were resolved conservatively without surgical intervention.

PMID- 25944149
TI  - Post-Transplant Hepatic Artery Pseudoaneurysm Treated with the Pipeline Flow
      Diverting Stent.

PMID- 25944150
TI  - Vascular Closure Devices in Interventional Radiology Practice.
AB  - Manual compression (MC) is a well-established technique for haemostasis following
      percutaneous arterial intervention. However, MC is labour and time intensive with
      potential limitations, particularly for patients who are coagulopathic, unable to
      comply with bed rest or obese and when large sheaths or anti-coagulants are used.
      There are a variety of vascular closure devices (VCDs) available to overcome
      these limitations. This review gives an overview of current VCDs, their mechanism
      of action, individual strengths and weaknesses, evidence base and utility in
      interventional radiology (IR) practice. The majority of the published evidence on
      VCDs is derived from patients undergoing cardiac interventions, which should be
      borne in mind when considering the applicability and transfer of this data for
      general IR practice. Overall, the evidence suggests that most VCDs are effective
      in achieving haemostasis with a similar rate of complications to MC although the
      complication profile associated with VCDs is distinct to that of MC. There is
      insufficient evidence to comparatively analyse the different types of VCDs
      currently available or reliably judge their cost-effectiveness. The
      interventional radiologist should have a thorough understanding of the available
      techniques for haemostasis and be able to identify and utilise the most
      appropriate strategy and closure technique for the individual patient. 

PMID- 25944151
TI  - Measuring the dynamic structure factor of a quantum gas undergoing a structural
      phase transition.
AB  - The dynamic structure factor is a central quantity describing the physics of
      quantum many-body systems, capturing structure and collective excitations of a
      material. In condensed matter, it can be measured via inelastic neutron
      scattering, which is an energy-resolving probe for the density fluctuations. In
      ultracold atoms, a similar approach could so far not be applied because of the
      diluteness of the system. Here we report on a direct, real-time and
      nondestructive measurement of the dynamic structure factor of a quantum gas
      exhibiting cavity-mediated long-range interactions. The technique relies on
      inelastic scattering of photons, stimulated by the enhanced vacuum field inside a
      high finesse optical cavity. We extract the density fluctuations, their energy
      and lifetime while the system undergoes a structural phase transition. We observe
      an occupation of the relevant quasi-particle mode on the level of a few
      excitations, and provide a theoretical description of this dissipative quantum
      many-body system. 

PMID- 25944152
TI  - Porous silica particles grafted with an amphiphilic side-chain polymer as a
      stationary phase in reversed-phase high-performance liquid chromatography.
AB  - The amphiphilic polymer-grafted silica was newly prepared as a stationary phase
      in high-performance liquid chromatography. Poly(4-vinylpyridine) with a
      trimethoxysilyl group at one end was grafted onto porous silica particles and the
      pyridyl side chains were quaternized with 1-bromooctadecane. The obtained
      poly(octadecylpyridinium)-grafted silica was characterized by elemental analysis,
      diffuse reflectance infrared Fourier transform spectroscopy and Brunauer-Emmett
      Teller analysis. The degree of quaternization of the pyridyl groups on the
      obtained stationary phase was estimated to be 70%. The selective retention
      behaviors of polycyclic aromatic hydrocarbons including some positional isomers
      were investigated using poly(octadecylpyridinium)-grafted silica as an
      amphiphilic polymer stationary phase in high-performance liquid chromatography
      and results were compared with commercially available polymeric octadecylated
      silica and phenyl-bonded silica columns. The results indicate that the
      selectivity toward polycyclic aromatic hydrocarbons exhibited by the amphiphilic
      polymer stationary phase is higher than the corresponding selectivity exhibited
      by a conventional phenyl-bonded silica column. However, compared with the
      polymeric octadecylated silica phase, the new stationary phase presents similar
      retention behavior for polycyclic aromatic hydrocarbons but different retention
      behavior particularly for positional isomers of disubstituted benzenes as the
      aggregation structure of amphiphilic polymers on the surface of silica substrate
      has been altered during mobile phase variation. 

PMID- 25944153
TI  - Drinking water studies: a review on heavy metal, application of biomarker and
      health risk assessment (a special focus in Malaysia).
AB  - Malaysia has abundant sources of drinking water from river and groundwater.
      However, rapid developments have deteriorated quality of drinking water sources
      in Malaysia. Heavy metal studies in terms of drinking water, applications of
      health risk assessment and bio-monitoring in Malaysia were reviewed from 2003 to
      2013. Studies on heavy metal in drinking water showed the levels are under the
      permissible limits as suggested by World Health Organization and Malaysian
      Ministry of Health. Future studies on the applications of health risk assessment
      are crucial in order to understand the risk of heavy metal exposure through
      drinking water to Malaysian population. Among the biomarkers that have been
      reviewed, toenail is the most useful tool to evaluate body burden of heavy metal.
      Toenails are easy to collect, store, transport and analysed. This review will
      give a clear guidance for future studies of Malaysian drinking water. In this
      way, it will help risk managers to minimize the exposure at optimum level as well
      as the government to formulate policies in safe guarding the population. 

PMID- 25944154
TI  - First and second line drug resistance among treatment naive pulmonary
      tuberculosis patients in a district under Revised National Tuberculosis Control
      Programme (RNTCP) in New Delhi.
AB  - There is limited information of level of drug resistance to first-line and second
      line anti-tuberculosis agents in treatment naive pulmonary tuberculosis (PTB)
      patients from the Indian region. Therefore, the present prospective study was
      conducted to determine the antimicrobial susceptibility to first-line and second
      line anti-TB drug resistance in such patients. Sputum samples from consecutive
      treatment naive PTB cases registered in Lala Ram Sarup (LRS) district, under
      RNTCP containing 12 Directly Observed Treatment Centre's (DOTS), were enrolled
      using cluster sampling technology. A total of 453 samples were received from July
      2011 to June 2012. All samples were cultured on solid medium followed by drug
      susceptibility to first and second line anti-tubercular drugs as per RNTCP
      guidelines. Primary multi-drug resistance (MDR) was found to be 18/453; (4.0%).
      Extensively drug resistance (XDR) was found in one strain (0.2%), which was found
      to be resistant to other antibiotics. Data of drug resistant tuberculosis among
      treatment naive TB patients are lacking in India. The presence of XDR-TB and high
      MDR-TB in small population studied, calls for conducting systematic multi-centric
      surveillance across the country. 

PMID- 25944155
TI  - (13) CO2 /(12) CO2 exchange fluxes in a clamp-on leaf cuvette: disentangling
      artefacts and flux components.
AB  - Leaks and isotopic disequilibria represent potential errors and artefacts during
      combined measurements of gas exchange and carbon isotope discrimination (Delta).
      This paper presents new protocols to quantify, minimize, and correct such
      phenomena. We performed experiments with gradients of CO2 concentration (up to +/
      250 MUmol mol(-1) ) and delta(13) CCO2 (340/00), between a clamp-on leaf cuvette
      (LI-6400) and surrounding air, to assess (1) leak coefficients for CO2 , (12) CO2
      , and (13) CO2 with the empty cuvette and with intact leaves of Holcus lanatus
      (C3 ) or Sorghum bicolor (C4 ) in the cuvette; and (2) isotopic disequilibria
      between net photosynthesis and dark respiration in light. Leak coefficients were
      virtually identical for (12) CO2 and (13) CO2 , but ~8 times higher with leaves
      in the cuvette. Leaks generated errors on Delta up to 60/00 for H. lanatus and
      20/00 for S. bicolor in full light; isotopic disequilibria produced similar
      variation of Delta. Leak errors in Delta in darkness were much larger due to
      small biological : leak flux ratios. Leak artefacts were fully corrected with
      leak coefficients determined on the same leaves as Delta measurements. Analysis
      of isotopic disequilibria enabled partitioning of net photosynthesis and dark
      respiration, and indicated inhibitions of dark respiration in full light (H.
      lanatus: 14%, S. bicolor: 58%).

PMID- 25944156
TI  - Topical and intravenous tranexamic acid reduce blood loss compared to routine
      hemostasis in total knee arthroplasty: a multicenter, randomized, controlled
      trial.
AB  - INTRODUCTION: Tranexamic acid (TXA) is becoming widely used in orthopedic surgery
      to reduce blood loss and transfusion requirements, but consensus is lacking
      regarding the optimal route and dose of administration. The aim of this study was
      to compare the efficacy and safety of topical and intravenous routes of TXA with
      routine hemostasis in patients undergoing primary total knee arthroplasty (TKA).
      MATERIALS AND METHODS: We performed a randomized, multicenter, parallel, open
      label clinical trial in adult patients undergoing primary TKA. Patients were
      divided into three groups of 50 patients each: Group 1 received 1 g topical TXA,
      Group 2 received 2 g intravenous TXA, and Group 3 (control group) had routine
      hemostasis. The primary outcome was total blood loss. Secondary outcomes were
      hidden blood loss, blood collected in drains, transfusion rate, number of blood
      units transfused, adverse events, and mortality. RESULTS: One hundred and fifty
      patients were included. Total blood loss was 1021.57 (481.09) mL in Group 1,
      817.54 (324.82) mL in Group 2 and 1415.72 (595.11) mL in Group 3 (control group).
      Differences in total blood loss between the TXA groups and the control group were
      clinically and statistically significant (p < 0.001). In an exploratory analysis
      differences between the two TXA groups were not statistically significant (p =
      0.073) Seventeen patients were transfused. Transfusion requirements were
      significantly higher in Group 3 (p = 0.005). No significant differences were
      found between groups regarding adverse events. CONCLUSION: We found that 1 g of
      topical TXA and 2 g of intravenous TXA were both safe strategies and more
      effective than routine hemostasis to reduce blood loss and transfusion
      requirements after primary TKA. LEVEL OF EVIDENCE: I.

PMID- 25944157
TI  - The natural history of rotator cuff tears: a systematic review.
AB  - PURPOSE: To analyse the current scientific evidence regarding the natural history
      of the clinical and anatomical progression of rotator cuff tears. METHODS: A
      broad systematic review of the literature (PubMed database through January 2014)
      which was guided, conducted and reported according to PRISMA criteria. This
      article focuses on the rotator cuff tears. Articles had to meet an inclusion
      criteria. The methodological quality of each study was individually assessed
      using a recently developed general assessment tool AMQPP (assessing the
      methodological quality of published papers). RESULTS: Seven articles dealing with
      rotator cuff tears were included, one of them was a high-quality study. Three
      papers assessed the natural history and the natural course of rotator cuff
      rupture directly. The other studies indirectly assessed the natural history with
      reports on non-operative and operative therapy trends. All of these articles had
      been published in four different top medical journals according to 2013 ranking.
      We found no articles which clearly referred to the role of regression to the mean
      of rotator cuff tears. CONCLUSION: The development of symptoms and anatomical
      deterioration are often directly correlated. Spontaneous recovery to normal
      levels of function has been successfully achieved, and standardised non-operative
      treatment programmes are an effective alternative to surgery for many patients.
      Follow-up is necessary to avoid irreparable stage. However, surgery is still
      favoured by young active people and highly professional persons who need to get
      fit in a short period of time. Further research is still necessary. The AMQPP
      score system is simple and reliable. It works as a quick quality-checking tool
      which helps researchers to identify the key points in each paper and reach a
      decision regarding the eligibility of the paper more easily.

PMID- 25944158
TI  - MSAP markers and global cytosine methylation in plants: a literature survey and
      comparative analysis for a wild-growing species.
AB  - Methylation of DNA cytosines affects whether transposons are silenced and genes
      are expressed, and is a major epigenetic mechanism whereby plants respond to
      environmental change. Analyses of methylation-sensitive amplification
      polymorphism (MS-AFLP or MSAP) have been often used to assess methyl-cytosine
      changes in response to stress treatments and, more recently, in ecological
      studies of wild plant populations. MSAP technique does not require a sequenced
      reference genome and provides many anonymous loci randomly distributed over the
      genome for which the methylation status can be ascertained. Scoring of MSAP data,
      however, is not straightforward, and efforts are still required to standardize
      this step to make use of the potential to distinguish between methylation at
      different nucleotide contexts. Furthermore, it is not known how accurately MSAP
      infers genome-wide cytosine methylation levels in plants. Here, we analyse the
      relationship between MSAP results and the percentage of global cytosine
      methylation in genomic DNA obtained by HPLC analysis. A screening of literature
      revealed that methylation of cytosines at cleavage sites assayed by MSAP was
      greater than genome-wide estimates obtained by HPLC, and percentages of
      methylation at different nucleotide contexts varied within and across species.
      Concurrent HPLC and MSAP analyses of DNA from 200 individuals of the perennial
      herb Helleborus foetidus confirmed that methyl-cytosine was more frequent in CCGG
      contexts than in the genome as a whole. In this species, global methylation was
      unrelated to methylation at the inner CG site. We suggest that global HPLC and
      context-specific MSAP methylation estimates provide complementary information
      whose combination can improve our current understanding of methylation-based
      epigenetic processes in nonmodel plants.

PMID- 25944159
TI  - Dietary patterns and their associations with childhood obesity in China.
AB  - Dietary patterns represent the combined effects of foods, and illustrate
      efficaciously the impact of diet on health outcomes. Some findings of previous
      studies have limited applicability to Chinese children due to cultural factors.
      The present study was designed to identify dietary patterns and determine their
      relationships with obesity among Chinese children and adolescents. Data collected
      from 1282 children and adolescents aged 7-17 years from the 2011 China Health and
      Nutrition Survey (CHNS) were used. Dietary patterns were identified using factor
      analysis of data from three consecutive 24-h dietary recalls. Weight and height
      were measured following standard methods, and BMI was calculated. Three dietary
      patterns were identified: modern (high intakes of milk, fast foods and eggs),
      traditional north (high intakes of wheat, tubers and other cereals) and
      traditional south (high intakes of vegetables, rice and pork). After adjusting
      for some confounders and total energy intake, subjects in the highest quartiles
      of the modern and traditional north patterns were found to have significantly
      greater risk of obesity (OR 3.10, 95 % CI 1.52, 6.32, and OR 2.42, 95 % CI 1.34,
      4.39, respectively). In conclusion, the modern dietary pattern and the
      traditional north dietary pattern were associated with higher risk of obesity.
      Promoting healthier eating patterns could help prevent obesity in Chinese
      children.

PMID- 25944160
TI  - Antioxidant Activity of Oxygen Evolving Enhancer Protein 1 Purified from
      Capsosiphon fulvescens.
AB  - This study was conducted to determine the antioxidant activity of a protein
      purified from Capsosiphon fulvescens. The purification steps included sodium
      acetate (pH 6) extraction and diethylaminoethyl-cellulose, reversed phase Shodex
      C4P-50 column chromatography. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis analysis indicated that the molecular weight of the purified
      protein was 33 kDa. The N-terminus and partial peptide amino acid sequence of
      this protein was identical to the sequence of oxygen evolving enhancer (OEE) 1
      protein. The antioxidant activity of the OEE 1 was determined in vitro using a
      scavenging test with 4 types of reactive oxygen species (ROS), including the 2,2
      diphenyl-1-picrylhydrazyl radical, hydroxyl radical, superoxide anion, and
      hydrogen peroxide (H2 O2 ). OEE 1 had higher H2 O2 scavenging activity, which
      proved to be the result of enzymatic antioxidants rather than nonenzymatic
      antioxidants. In addition, OEE 1 showed less H2 O2 -mediated ROS formation in
      HepG2 cells. In conclusion, this study demonstrates that OEE 1 purified from C.
      fulvescens is an excellent antioxidant. 

PMID- 25944161
TI  - DNA double-strand break repair gene XRCC7 genotypes were associated with
      hepatocellular carcinoma risk in Taiwanese males and alcohol drinkers.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, the
      prevalence and mortality rates of which are very high in Taiwan. The study aimed
      at evaluating the contribution of XRCC7 G6721T, together with cigarette smoking
      and alcohol drinking lifestyles, to the risk of HCC. In this hospital-based case
      control study, the association of XRCC7 single nucleotide polymorphism G6721T
      with HCC risk was examined by polymerase chain reaction (PCR)-restriction
      fragment length polymorphism (RFLP) among 298 HCC patients and 889 age- and
      gender-matched healthy controls. The results showed that the percentages of TT,
      GT, and GG XRCC7 G6721T were 53.0, 41.3, and 5.7 % in the HCC patient group and
      48.9, 43.1, and 8.0 % in the non-cancer control group, respectively. We have
      further stratified the populations by genders, cigarette smoking, and alcohol
      drinking status to investigate their combinative contributions with XRCC7 G6721T
      genotype to HCC risk. The results showed that the GG genotype of XRCC7 G6721T
      conducted a protective effect on HCC susceptibility which was obvious among males
      and drinkers, but not females, smokers, non-smokers, or non-drinkers (p = 0.0058,
      0.0069, 0.1564, 0.2469, 0.9354, and 0.3416, respectively). Our results suggested
      that the GG and GT genotypes of X-ray repair cross-complementing group 7 (XRCC7)
      G6721T had no effect on HCC risk to the whole population, but had a protective
      effect on HCC risk among males and alcohol drinkers.

PMID- 25944162
TI  - Association between donor and recipient smoothened gene polymorphisms and the
      risk of hepatocellular carcinoma recurrence following orthotopic liver
      transplantation in a Han Chinese population.
AB  - Hepatocellular carcinoma (HCC) recurrence after orthotopic liver transplantation
      (OLT) is potential cause for the poor outcome. Smoothened (SMO) gene has been
      considered associating with HCC and HCC recurrence, but its association with HCC
      recurrence after OLT is not clear yet. In this study, we aim at evaluating the
      association between donor and recipient SMO gene polymorphisms and HCC recurrence
      after OLT. A total of 76 patients with HCC who had undergone OLT from July 2007
      to August 2012 were included. A single nucleotide polymorphism (SNP), SMO rs3824,
      located at the 3'UTR region, was genotyped and analyzed in both donor and
      recipient. We demonstrated that recipient rs3824 polymorphism was significantly
      associated with HCC recurrence following OLT. In multivariate logistic regression
      analysis, TNM stage (p = 0.001), recipient SMO rs3824 genotype (CG vs. CC/GG p =
      0.001), and histologic grade (p = 0.019) were identified as independent risk
      factors of HCC recurrence. Recurrence-free survival (RFS) and overall survival
      (OS) were significantly higher in the recipient CC/GG group than in the CG group
      (p = 0.003 and p = 0.011, respectively). Cox proportional hazards modeling
      revealed that TNM stage, recipient SMO rs3824 genotype, pre-OLT serum AFP level,
      and histologic grade were independent factors (p < 0.05) for patients' clinical
      outcomes. In conclusion, recipient SMO rs3824 polymorphism is associated with an
      increased risk of HCC recurrence following OLT and has a potential clinical value
      for the prognosis of HCC patients treated with OLT.

PMID- 25944163
TI  - Intratumoral neutrophil granulocytes contribute to epithelial-mesenchymal
      transition in lung adenocarcinoma cells.
AB  - We previously demonstrated that haemoptysis as a prognostic factor in lung
      adenocarcinoma and haemoptysis was associated with severe vascular invasion and
      high circulating white blood cell count. Epithelial-mesenchymal transition (EMT)
      plays an important role in tumor invasion. We hypothesized there was some
      relationship between tumor-associated inflammatory cells, tumor invasion, EMT,
      and haemoptysis. Immunohistochemistry (IHC) was used to detect CD66b and E
      cadherin expression in tumor tissue. By co-culture tumor cells with
      polymorphonuclear neutrophils (PMNs), the expressions of EMT markers were
      assessed by western blotting. TGF-beta1 concentrations in the supernatant and the
      migration activities of tumor cells were performed by ELISA and migration assays.
      Intratumoral CD66b(+) PMN expression was negatively associated with E-cadherin
      expression. Haemoptysis was significantly associated with neutrophil infiltration
      (OR = 4.25, 95 % CI 1.246-14.502). Neutrophils promoted EMT of tumor cells in
      vitro and enhanced the migration activity of tumor cells. In addition, TGF-beta1
      was up-regulated and Smad4 translocated into nucleus, indicating that TGF
      beta/Smad signaling pathway was initiated during the process. We indicated that
      lung adenocarcinoma with haemoptysis was associated with more PMN infiltration
      and PMNs promoted EMT, partly via TGF-beta/Smad signal pathway. This may provide
      mechanistic reasons for why haemoptysis was associated with poor outcome in lung
      adenocarcinoma.

PMID- 25944164
TI  - The role of osteopontin expression in melanoma progression.
AB  - It was shown that osteopontin (OPN), a glycophosphoprotein, plays divergent roles
      in cancer progression. In addition to multiple intra- and extracellular
      functions, it facilitates migration of tumour cells, has crucial role in cell
      adhesion and is associated with increased metastasis formation. In previous
      studies, we performed global gene expression profiling on a series of primary
      melanoma samples and found that OPN was significantly overexpressed in ulcerated
      melanomas. The major purpose of this study was to define OPN expression in
      primary melanomas with differing biological behaviours. OPN mRNA expression was
      analysed by quantitative reverse transcription polymerase chain reaction (qRT
      PCR) in primary melanoma tissues. Immunohistochemistry was performed using a
      tissue microarray. Cox regression tests were used for survival analysis. Greater
      than 50 % of the tissues exhibited high protein expression that was significantly
      associated with tumour thickness and metastasis. OPN mRNA expression was
      significantly increased in thicker melanomas and lesions with an ulcerated
      surface. Increased expression was primarily detected in advanced-stage tumours. A
      multivariate Cox regression analysis revealed that high OPN expression, tumour
      thickness and metastasis were significantly associated with reduced relapse-free
      survival. In summary, high OPN mRNA and protein expression were associated with a
      less favourable clinical outcome of primary melanoma patients. We determined that
      OPN is a significant predictive factor for the survival of primary melanoma
      patients. Based on our and others data, the high expression of OPN may have a
      crucial stimulatory role in tumour progression and metastasis formation, which,
      thus, have been proposed as potential targets for cancer diagnosis and therapy.

PMID- 25944165
TI  - The elevated pretreatment platelet-to-lymphocyte ratio predicts poor outcome in
      nasopharyngeal carcinoma patients.
AB  - The aim of this study was to evaluate whether the platelet-to-lymphocyte ratio
      (PLR) could be used to predict the prognosis of patients with nasopharyngeal
      carcinoma (NPC). Patients (n = 1261) who were diagnosed with nonmetastatic NPC
      between January 2008 and December 2010 were recruited. The peripheral platelet
      and lymphocyte counts were retrieved, and the PLR was calculated. Univariate and
      multivariate Cox proportional hazards analyses were used to assess their
      association with PLR: overall survival (OS), cancer-specific survival (CSS), and
      distant metastasis-free survival (DMFS). The elevated PLR, using the third
      quartile values (153.64) as the optimal cutoff values, was found to be associated
      with the significant decline in CSS (hazard ratio [HR] 1.83, 95 % confidence
      interval [CI] 1.27-2.63, P < 0.001), OS (HR 1.81, 95 % CI 1.28-2.56, P < 0.001),
      and DMFS (HR 1.60, 95 % CI 1.15-2.23, P = 0.005) that remained significant during
      the multivariable analyses (CCS HR 1.84, 95 % CI 1.26-2.67, P < 0.001; OS HR
      1.83, 95 % CI 1.28-2.61, P < 0.001; DMFS HR 1.56, 95 % CI 1.11-2.19, P = 0.011).
      Subgroup analyses indicated that the PLR could be used to stratify prognosis
      effectively for patients with early- or advanced-stage NPC, and Epstein-Barr
      virus DNA levels of >=1500 copies/mL. In conclusions, elevated PLR values were
      associated with poor CSS, OS, and DMFS for patients with NPC; this easily
      accessed variable based on a large amount of cases multivariate analysis is
      valuable for predicting prognosis in patients with NPC.

PMID- 25944166
TI  - MicroRNA-25 promotes gastric cancer proliferation, invasion, and migration by
      directly targeting F-box and WD-40 Domain Protein 7, FBXW7.
AB  - Increasing evidence shows that abnormal microRNA (miRNA) expression is involved
      in tumorigenesis. MiR-25 was previously reported to act as tumor suppressor or
      oncogene in diverse cancers. However, their expression, function, and mechanism
      in gastric cancer (GC) are not well known. Here, we show that miR-25 was
      overexpressed in primary tumor tissues of GC patients and was significantly
      correlated with a more aggressive phenotype of GC in patients. MiR-25 inhibition
      significantly decreased the proliferation, invasion, and migration of GC cells in
      vitro. Furthermore, miR-25 repressed F-box and WD-40 domain protein 7 (FBXW7)
      expression by directly binding to 3-untranslated region (UTR) of FBXW7, and the
      inverse correlation was observed between the expressions of miR-25 and FBXW7 mRNA
      in primary GC tissues. Moreover, the restoration of FBXW7 led to suppressed
      proliferation, invasion, and migration of GC cells. In vivo, miR-25 promotes
      tumor growth of GC. Taken together, miR-25 promotes GC progression by directly
      downregulating FBXW7 expression and may be employed as a novel prognostic marker
      and therapeutic target of GC.

PMID- 25944167
TI  - Susceptibility to oral cancers with CD95 and CD95L promoter SNPs may vary with
      the site and gender.
AB  - We investigated risk association of oral cancers (tongue and buccal mucosa
      cancers) with FAS (-1377G > A and FAS -670 A > G) and FASL (-844 T > C) SNPs, in
      males and females. A case-control study of 535 oral cancer and 525 control
      subjects was performed. SNPs were detected in the genomic DNA isolated from
      peripheral blood using PCR-RFLP. We report FASL -844 T > C SNPs increased risk
      for buccal mucosa cancer in females but not in males. On the other hand, FAS
      genotypes did not alter the risk of the cancers in both females and males.
      However, co-occurrence of FAS -1377 GA and -670 GG, FAS -1377 AA and -670 GG
      genotypes, and combined genotypes of FAS and FASL (FAS -1377 AA + FAS -670 GG +
      FASL -844 CC) alter male susceptibility towards tongue cancer. In females,
      combined genotypes of FAS (-1377GA and -670 AA) were found to be a risk factor of
      buccal mucosa cancer (OR = 3.27, CI = 1.28-8.36; P <= 0.01). FASL variants (GA
      and AA) increased tongue cancer risk in females who were tobacco users compared
      to non-tobacco users. In conclusion, SNPs of the FAS and FASL might alter risk of
      tongue and buccal mucosa cancers differentially, in a gender-dependent manner.

PMID- 25944168
TI  - Anti-STMN1 therapy improves sensitivity to antimicrotubule drugs in esophageal
      squamous cell carcinoma.
AB  - Stathmin (STMN1) regulates microtubule dynamics by promoting depolymerization of
      microtubules and/or preventing polymerization of tubulin heterodimers. Several
      studies have shown that overexpression of STMN1 has been linked to
      chemoresistance of paclitaxel and vinblastine in tumor cells. This study aimed to
      investigate the effects of STMN1 silencing on chemosensitivities of paclitaxel or
      vinblastine in esophageal squamous cell carcinoma (ESCC). Immunocytochemistry and
      immunofluorescence assays showed that STMN1 gene was highly expressed in Eca109
      and TE-1 cells. We demonstrated that lentiviral-mediated STMN1 short hairpin RNA
      (shRNA) specifically and efficiently downregulated STMN1 expression in Eca109 and
      TE-1 cells. The sensitivity of STMN1-silencing shRNA-transfected Eca109 and TE-1
      cells increased 191.4- and 179.3-fold to paclitaxel, and 21.3- and 28.4-fold to
      vincristine, respectively. Flow cytometry and mitotic index assays showed that
      knockdown of STMN1 in Eca109 and TE-1 cells led to cell cycle arrest in G2/M
      phase. After treatment with paclitaxel or vincristine, STMN1-silencing shRNA
      transfected Eca109 and TE-1 cells were more likely to enter G2 but less likely to
      enter mitosis than control cells. Therefore, these data suggests that silencing
      STMN1 gene could increase sensitivity of ESCC to paclitaxel and vincristine
      through G2/M phase block.

PMID- 25944169
TI  - Intramuscular injection of mitomycin C combined with endoscopic dilation for
      benign esophageal strictures.
AB  - OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of
      intramuscular injection of either mitomycin C or dexamethasone with endoscopic
      dilation for benign esophageal strictures after esophageal surgery or endoscopic
      submucosal dissection. METHODS: Patients with benign esophageal strictures were
      retrospectively enrolled in this study and divided into three groups: mitomycin C
      group (mitomycin C injection with endoscopic dilation, dexamethasone group
      (dexamethasone injection and dilation) and dilation group (physiological saline
      injection and dilation). The patients' characteristics, locations of lesions,
      number of previous dilations, esophageal diameters after dilation, grades of
      dysphagia before and after the procedure and dysphagia-free period during the
      follow-up period were recorded. RESULTS: Altogether 74 patients including 25 in
      the mitomycin C group, 25 in the dexamethasone group and 24 in the dilation group
      were enrolled. The diameter of the esophagus before the procedure was 3.32 +/-
      0.90 mm, 3.92 +/- 1.55 mm and 3.70 +/- 1.30 mm, respectively, while that was
      increased to 12.77 +/- 1.62 mm, 12.14 +/- 1.28 mm and 12.73 +/- 1.42 mm after
      endoscopic dilation in the mitomycin C, dexamethasone and conventional dilation
      groups. The dysphagia-free period was 4.88 +/- 1.66 months in the mitomycin C
      group, 4.02 +/- 1.77 months in the dexamethasone group and 2.41 +/- 1.26 months
      in the dilation group (P < 0.05). CONCLUSION: Intramuscular injection of
      mitomycin C or dexamethasone may prolong the dysphagia-free period and decrease
      the frequency of repeat dilations compared with conventional endoscopic dilations
      in patients with benign esophageal strictures.

PMID- 25944171
TI  - Start-up designs for response-adaptive randomization procedures with sequential
      estimation.
AB  - Response-adaptive randomization procedures are appropriate for clinical trials in
      which two or more treatments are to be compared, patients arrive sequentially and
      the response of each patient is recorded before the next patient arrives.
      However, for those procedures that involve sequential estimation of model
      parameters, start-up designs are commonly required in order to provide initial
      estimates of the parameters. In this paper, a suite of such start-up designs for
      two treatments and binary patient responses are considered and compared in terms
      of the numbers of patients required in order to give meaningful parameters
      estimates, the number of patients allocated to the better treatment, and the bias
      in the parameter estimates. It is shown that permuted block designs with blocks
      of size 4 are to be preferred over a wide range of parameter values. For the case
      of two treatments, normal responses and selected start-up procedures, a design
      incorporating complete randomization followed appropriately by repeats of one of
      the treatments yields the minimum expected number of patients and is to be
      preferred.

PMID- 25944170
TI  - Body image dissatisfaction and eating-related psychopathology in trans
      individuals: a matched control study.
AB  - High levels of body dissatisfaction have already been reported in the trans
      population; however, the root of this dissatisfaction, and its association with
      eating disordered behaviours, has not been studied in-depth. This study aims to
      assess eating disorder risk by comparing 200 trans people, 200 people with eating
      disorders and 200 control participants' scores on three subscales of the Eating
      Disorders Inventory-2 (EDI-2) and to further explore dissatisfaction in the trans
      participants using the Hamburg Body Drawing Scale (HBDS). The results showed that
      overall participants with eating disorders scored higher than trans or control
      groups on all EDI-2 measures, but that trans individuals had greater body
      dissatisfaction than control participants and, importantly, trans males had
      comparable body dissatisfaction scores to eating disordered males. Drive for
      thinness was greater in females (cis and trans) compared with males. In relation
      to HBDS body dissatisfaction, both trans males and trans females reported
      greatest dissatisfaction not only for gender-identifying body parts but also for
      body shape and weight. Overall, trans males may be at particular risk for eating
      disordered psychopathology and other body image-related behaviours.

PMID- 25944172
TI  - Successful delivery after transabdominal cerclage of uterine cervix for cervical
      incompetence after radical trachelectomy.
AB  - Pregnancy after radical trachelectomy (RT) has a high risk of prematurity and
      complications such as preterm premature rupture of the membrane and
      chorioamnionitis. Placing a cervical cerclage at the time of RT plays an
      important role in preventing such obstetrical complications. In patients who have
      trouble with the cervical cerclage, miscarriage during the second trimester seems
      to be inevitable. We have therefore started preconception transabdominal cerclage
      (TAC) for these patients. A 36-year-old Japanese woman who had a history of
      miscarriage due to trouble with the nylon thread used for cerclage, successfully
      delivered after TAC. TAC is a useful treatment modality to prevent miscarriage
      for patients who have trouble with cerclage after RT.

PMID- 25944173
TI  - Correction: Transcription of 4'-thioDNA templates to natural RNA in vitro and in
      mammalian cells.

PMID- 25944174
TI  - Model for bidirectional movement of cytoplasmic dynein.
AB  - Cytoplasmic dynein exhibits a directional processive movement on microtubule
      filaments and is known to move in steps of varying length based on the number of
      ATP molecules bound to it and the load that it carries. It is experimentally
      observed that dynein takes occasional backward steps and the frequency of such
      backward steps increases as the load approaches the stall force. Using a
      stochastic process model, we investigate the bidirectional movement of single
      head of a dynein motor. The probability for backward step is implemented based on
      fluctuation theorem of non-equilibrium statistical mechanics. We find that the
      movement of dynein motor is characterized with negative velocity implying
      backward motion beyond stall force. We observe that the motor moves backward for
      super stall forces by hydrolyzing the ATP exactly the same way as it does while
      moving forward for sub-stall forces. Movement of dynein is also simulated using a
      kinetic Monte Carlo method and the simulated velocities are in good agreement
      with velocities obtained using a stochastic rate equation model. 

PMID- 25944175
TI  - An approach for de-identification of point locations of livestock premises for
      further use in disease spread modeling.
AB  - We describe a method for de-identifying point location data used for disease
      spread modeling to allow data custodians to share data with modeling experts
      without disclosing individual farm identities. The approach is implemented in an
      open-source software program that is described and evaluated here. The program
      allows a data custodian to select a level of de-identification based on the K
      anonymity statistic. The program converts a file of true farm locations and
      attributes into a file appropriate for use in disease spread modeling with the
      locations randomly modified to prevent re-identification based on location.
      Important epidemiological relationships such as clustering are preserved to as
      much as possible to allow modeling similar to those using true identifiable data.
      The software implementation was verified by visual inspection and basic
      descriptive spatial analysis of the output. Performance is sufficient to allow de
      identification of even large data sets on desktop computers available to any data
      custodian. 

PMID- 25944176
TI  - Development of a HACCP-based approach to control paratuberculosis in infected
      Irish dairy herds.
AB  - Paratuberculosis is a challenging disease to control at farm level, in part due
      to the poor sensitivity of diagnostic tests and a prolonged incubation period.
      Simulation studies have highlighted on-farm management to be the most important
      factor in preventing on-farm spread. A risk assessment (RA) and management plan
      (MP) approach (collectively, RAMP) has been adopted around the world as the most
      appropriate method of controlling disease in infected farms. However, there are
      problems with RAMP that remain to be resolved. The RA relies heavily on farmer
      recollection and estimation resulting in subjectivity and substantial inter
      observer variability. MPs consist of a series of qualitative, farm specific
      recommendations showing how management can be improved. However, MP assessment is
      generally conducted informally, and progress is monitored through 'end-point'
      diagnostic testing of adult animals and repeated risk assessments. Hazard
      analysis and critical control point (HACCP) has been developed as a proactive
      alternative to end-point testing. We hypothesise that farm-based HACCP systems
      may be a useful alternative to RAMP on farms where more intensive monitoring and
      evaluation of controls for paratuberculosis is required. Therefore, the objective
      of this methodological study was to develop a HACCP-based system for
      paratuberculosis control. Critical control points (CCPs) relating to peri
      parturient area management, calving, new-born calf management and colostrum
      management were identified as areas where additional control could be exerted
      above existing methods. Novel monitoring systems were developed for each CCP,
      along with targets and corrective actions. This system is intended for use in
      high prevalence herds, or farms where more robust monitoring of key control
      points may be beneficial. It is currently being trialled on infected commercial
      dairy herds in Ireland. 

PMID- 25944178
TI  - Associated decrements in rate of force development and neural drive after maximal
      eccentric exercise.
AB  - The present study investigated the changes in contractile rate of force
      development (RFD) and the neural drive following a single bout of eccentric
      exercise. Twenty-four subjects performed 15 * 10 maximal isokinetic eccentric
      knee extensor contractions. Prior to and at 24, 48, 72, 96, and 168 h during post
      exercise recovery, isometric RFD (30, 50 100, and 200 ms), normalized RFD
      [1/6,1/2, and 2/3 of maximal voluntary contraction (MVC)] and rate of
      electromyography rise (RER; 30, 50, and 75 ms) were measured. RFD decreased by 28
      42% peaking at 48 h (P < 0.01-P < 0.001) and remained depressed at 168 h (P <
      0.05). Normalized RFD at 2/3 of MVC decreased by 22-39% (P < 0.01), peaked at 72
      h and returned to baseline at 168 h. These changes in RFD were associated with a
      decrease in RER at 48 h-96 h (P < 0.05-P < 0.001). Accumulated changes (area
      under curve) revealed a greater relative decrease in accumulated RFD at 100 ms by
      -2727 +/- 309 (%h; P < 0.05) and 200 ms by -3035 +/- 271 (%h; P < 0.001) compared
      with MVC, which decreased, by -1956 +/- 234 (%h). In conclusion, RFD and RER are
      both markedly reduced following a bout of maximal eccentric exercise. This
      association suggests that exercise-induced decrements in RFD can, in part, be
      explained decrements in neural drive. 

PMID- 25944177
TI  - What happens to patients when they fracture their hip during a skilled nursing
      facility stay?
AB  - OBJECTIVES: To characterize outcomes of patients experiencing a fall and
      subsequent hip fracture while in a nursing home receiving skilled nursing
      facility (SNF) services. DESIGN: Observational study. PARTICIPANTS: Short-stay
      fee-for-service Medicare beneficiaries who experienced their first hip fracture
      during an SNF stay. MEASUREMENTS: Outcomes measured in the 90 days after the hip
      fracture hospitalization included community discharge (with a stay in the
      community <30 days), successful community discharge (in the community >=30 days),
      death, and institutionalization. RESULTS: Between 1999 and 2007, 27,305 hip
      fractures occurred among short-stay nursing home patients receiving SNF care.
      After surgical repair of the hip fracture, 83.9% of these patients were
      discharged from the hospital back to an SNF, with most (99%) returning to the
      facility where the hip fracture occurred. In the first 90 days after
      hospitalization, 24.1% of patients died, 7.3% were discharged to the community
      but remained fewer than 30 days, 14.0% achieved successful community discharge,
      and 54.6% were still in a health care institution with almost 46.4% having
      transitioned to long-term care. CONCLUSION: SNF care aims to maximize the short
      stay patient's independence and facilitate a safe community transition. However,
      experiencing a fall and hip fracture during the SNF stay was a sentinel event
      that limited the achievement of this goal. There is an urgent need to ensure the
      integration of fall prevention into the patient's plan of care. Further, falls
      among SNF patients may serve as indicator of quality, which consumers and payers
      can use to make informed health care decisions.

PMID- 25944179
TI  - A sensitive liquid chromatography-mass spectrometry bioanalytical assay for a
      novel anticancer candidate--ZMC1.
AB  - ZMC1 {azetidinecarbothioic acid, [1-(2-pyridinyl) ethylidene] hydrazide} is a
      lead compound being developed as one of the first mutant p53 targeted anti-cancer
      drugs. Establishing a precise quantitative method is an integral component of
      this development. The aim of this study was to develop a sensitive LC/MS/MS assay
      suitable for assessing purity, stability and preclinical pharmacokinetic studies
      of ZMC1. Acetonitrile protein precipitation extraction was chosen for plasma
      sample preparation with satisfactory recovery (84.2-92.8%) for ZMC1.
      Chromatographic separation was achieved on an Xterra C18 column (50 * 4.6 mm, 3.5
      um) using a gradient elution with mobile phase of 0.1% formic acid in water and
      acetonitrile. ZMC1 and internal standard 2-amino-6-bromobenzothiazole were
      identified using selected-ion monitoring mode at m/z 235.2/178.2 and m/z
      231.0/150.0 at retention times of 5.2 and 6.3 min, respectively. The method was
      validated with a linearity range of 3.9-500.0 ng/mL in human plasma and showed
      acceptable reproducibility with intra- and interday precisions <5.9 and 10.5%,
      and accuracy within +/-5.4% of nominal values. This analytical method together
      with basic stability data in plasma and plasma binding experiments provides a
      reliable protocol for the study of ZMC1 pharmacokinetics. This will greatly
      facilitate the pre-clinical development of this novel anti-cancer drug.

PMID- 25944180
TI  - Is waist circumference per body mass index rising differentially across the
      United States, England, China and Mexico?
AB  - BACKGROUND/OBJECTIVES: Little is known about whether waist circumference (WC) has
      increased disproportionately relative to body mass index (BMI) around the world.
      SUBJECTS/METHODS: Data came from the US National Health and Nutrition Examination
      Survey (1988-1994 and 2007-2010), Health Survey for England (1992-1993 and 2008
      2009); the Mexican Nutrition Survey (1999) and the Mexican National Health and
      Nutrition Survey (NHNS 2012); and the China Health and Nutrition Survey (1993 and
      2011). Country- and sex-stratified (for the United States, also race-/ethnicity
      stratified) multivariable linear regressions were used to estimate mean
      difference in WC over time relative to BMI at specified overweight and obesity
      cutoff points, adjusting for age and survey year. RESULTS: Although mean WC and
      BMI shifted upward over time in all age-sex subpopulations in all four countries,
      trends in overweight prevalence were less consistent. However, WC relative to BMI
      increased at varying magnitudes across all countries and subpopulations, except
      US Black men. The magnitude of increase was largest for women in the youngest age
      group (20-29 years), particularly for women in Mexico (+6.6 cm, P<0.0001) and
      China (+4.6 cm, P<0.0001) (holding BMI constant at 25 kg/m(2)). For men, the
      increase was primarily evident among Chinese men (+4.8 cm, P<0.0001).
      CONCLUSIONS: WC has increased disproportionately over time relative to overall
      body mass across the United States, England, Mexico and China, particularly among
      young women, with the largest increases occurring in the middle-income countries
      of Mexico and China. These patterns are potentially a cause for concern
      especially for countries undergoing rapid economic and nutritional transitions.

PMID- 25944181
TI  - Nut consumption and risk of colorectal cancer in women.
AB  - BACKGROUND/OBJECTIVES: Increasing nut consumption has been associated with
      reduced risk of obesity and type II diabetes, the risk factors for colorectal
      cancer. However, the association between nut consumption and colorectal cancer
      risk is unclear. We aimed to examine the association of long-term nut consumption
      with risk of colorectal cancer. SUBJECTS/METHODS: We prospectively followed
      75,680 women who were free of cancer at baseline in the Nurses' Health Study, and
      examined the association between nut consumption and colorectal cancer risk. Nut
      consumption was assessed at baseline and updated every 2-4 years. Relative risks
      (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox
      proportional hazards models. RESULTS: During 2,103,037 person-years of follow-up,
      we identified 1503 colorectal cancer cases. After adjustment for other known or
      suspected risk factors, women who consumed nuts 2 or more times per week (that
      is, ? 56 g per week) had a 13% lower risk of colorectal cancer compared with
      those who rarely consumed nuts, but the association was not statistically
      significant (RR: 0.87; 95% CI: 0.72-1.05; P-trend: 0.06). No association was
      observed for peanut butter. CONCLUSIONS: In this large prospective cohort of
      women, frequent nut consumption was not significantly associated with colorectal
      cancer risk after adjusting for other risk factors.

PMID- 25944182
TI  - Classifying Intersex in DSM-5: Critical Reflections on Gender Dysphoria.
AB  - The new diagnosis of Gender Dysphoria (GD) in the fifth edition of the Diagnostic
      and Statistical Manual of Mental Disorders (American Psychiatric Association,
      2013) defines intersex, renamed "Disorders of Sex Development" (DSD), as a
      specifier of GD. With this formulation, the status of intersex departs from prior
      editions, especially from the DSM-IV texts that defined intersex as an exclusion
      criterion for Gender Identity Disorder. Conversely, GD--with or without a DSD-
      can apply in the same manner to DSD and non-DSD individuals; it subsumes the
      physical condition under the mental "disorder." This conceptualization, I
      suggest, is unprecedented in the history of the DSM. In my view, it is the most
      significant change in the revised diagnosis, and it raises the question of the
      suitability of psychiatric diagnosis for individuals with intersex/DSD.
      Unfortunately, this fundamental question was not raised during the revision
      process. This article examines, historically and conceptually, the different
      terms provided for intersex/DSD in the DSM in order to capture the significance
      of the DSD specifier, and the reasons why the risk of stigma and misdiagnosis, I
      argue, is increased in DSM-5 compared to DSM-IV. The DSM-5 formulation is
      paradoxically at variance with the clinical literature, with intersex/DSD and
      transgender being conceived as incommensurable terms in their diagnostic and
      treatment aspects. In this light, the removal of intersex/DSD from the DSM would
      seem a better way to achieve the purpose behind the revised diagnosis, which was
      to reduce stigma and the risk of misdiagnosis, and to provide the persons
      concerned with healthcare that caters to their specific needs.

PMID- 25944183
TI  - The complex nature of practice and research in end of life and bereavement care
      in the critical care environment.

PMID- 25944184
TI  - CS-SCORE: Rapid identification and removal of human genome contaminants from
      metagenomic datasets.
AB  - Metagenomic sequencing data, obtained from host-associated microbial communities,
      are usually contaminated with host genome sequence fragments. Prior to performing
      any downstream analyses, it is necessary to identify and remove such
      contaminating sequence fragments. The time and memory requirements of available
      host-contamination detection techniques are enormous. Thus, processing of large
      metagenomic datasets is a challenging task. This study presents CS-SCORE--a novel
      algorithm that can rapidly identify host sequences contaminating metagenomic
      datasets. Validation results indicate that CS-SCORE is 2-6 times faster than the
      current state-of-the-art methods. Furthermore, the memory footprint of CS-SCORE
      is in the range of 2-2.5GB, which is significantly lower than other available
      tools. CS-SCORE achieves this efficiency by incorporating (1) a heuristic pre
      filtering mechanism and (2) a directed-mapping approach that utilizes a novel
      sequence composition metric (cs-score). CS-SCORE is expected to be a handy 'pre
      processing' utility for researchers analyzing metagenomic datasets. AVAILABILITY:
      For academic users, an implementation of CS-SCORE is freely available at:
      http://metagenomics.atc.tcs.com/cs-score (or)
      https://metagenomics.atc.tcs.com/preprocessing/cs-score.

PMID- 25944185
TI  - Attenuation of experimental asthma by mycobacterial protein combined with CpG
      requires a TLR9-dependent IFN-gamma-CCR2 signalling circuit.
AB  - BACKGROUND: Allergic asthma is a chronic pulmonary disease characterized by a Th2
      inflammatory response. The modulation of a Th2 immune response based on immune
      deviation to a Th1 pattern or induction and migration of regulatory T cells to
      the lungs constitutes one of the major therapeutic approaches that is being
      investigated for the treatment of allergic asthma. The potentials of
      Mycobacterium leprae 65-kD heat-shock protein or Toll-like receptor 9 ligand (CpG
      oligodeoxynucleotides) as immune modulators for the treatment of airway allergic
      disease have been studied individually. OBJECTIVE: Mycobacterial protein combined
      with CpG was used as immunotherapy for airway allergy. METHODS: Using an
      ovalbumin-induced asthma model, mice were sensitized and challenged, and then
      treated with mycobacterial heat-shock protein (Hsp65) combined with CpG. RESULTS:
      The treatment of mice with established allergy led to the attenuation of
      eosinophilia, Th2 cytokines and airway hyperresponsiveness. Hsp65 plus CpG
      treatment also induced an increase in OVA-specific IFN-gamma levels and in the
      frequency of lung inflammatory monocytes. Moreover, we show that the reduction of
      eosinophilia and the recruitment of inflammatory monocytes to the lungs required
      early triggering of TLR9, IFN-gamma and CCR2 by immunotherapy components.
      CONCLUSION: In addition to immune deviation to a Th1 response in the modulation
      of Th2 allergic inflammation, our findings also attribute an important role to
      the innate response mediated by TLR9, associated with the recruitment of CCR2
      dependent monocytes. CLINICAL RELEVANCE: Our findings show that the Hsp65/CpG
      treatment is a promising strategy for consideration in translational studies.

PMID- 25944187
TI  - [Structural quality and treatment guidelines for inpatient care].

PMID- 25944188
TI  - [Obituary for Prof. Dr. Kurt Heinrich].

PMID- 25944186
TI  - Aquaporin-4 regulates the velocity and frequency of cortical spreading depression
      in mice.
AB  - The astrocyte water channel aquaporin-4 (AQP4) regulates extracellular space
      (ECS) K(+) concentration ([K(+)]e) and volume dynamics following neuronal
      activation. Here, we investigated how AQP4-mediated changes in [K(+)]e and ECS
      volume affect the velocity, frequency, and amplitude of cortical spreading
      depression (CSD) depolarizations produced by surface KCl application in wild-type
      (AQP4(+/+)) and AQP4-deficient (AQP4(-/-)) mice. In contrast to initial
      expectations, both the velocity and the frequency of CSD were significantly
      reduced in AQP4(-/-) mice when compared with AQP4(+/+) mice, by 22% and 32%,
      respectively. Measurement of [K(+)]e with K(+)-selective microelectrodes
      demonstrated an increase to ~35 mM during spreading depolarizations in both
      AQP4(+/+) and AQP4(-/-) mice, but the rates of [K(+)]e increase (3.5 vs. 1.5
      mM/s) and reuptake (t1/2 33 vs. 61 s) were significantly reduced in AQP4(-/-)
      mice. ECS volume fraction measured by tetramethylammonium iontophoresis was
      greatly reduced during depolarizations from 0.18 to 0.053 in AQP4(+/+) mice, and
      0.23 to 0.063 in AQP4(-/-) mice. Analysis of the experimental data using a
      mathematical model of CSD propagation suggested that the reduced velocity of CSD
      depolarizations in AQP4(-/-) mice was primarily a consequence of the slowed
      increase in [K(+)]e during neuronal depolarization. These results demonstrate
      that AQP4 effects on [K(+)]e and ECS volume dynamics accelerate CSD propagation.

PMID- 25944189
TI  - Novel lymphocyte screening tube using dried monoclonal antibody reagents.
AB  - We previously developed a 10-color 11-antibody combination including a viability
      dye, to screen T-, B-, and natural killer (NK)-cell populations in blood, bone
      marrow, tissue, and body fluids. Recently, Beckman Coulter has introduced a line
      of dried reagents that, unlike liquid reagents and cocktails, require no
      refrigeration, titration, or manipulation before using. We evaluated custom tubes
      based on our standard lymphocyte screening panel, focusing on comparative
      analysis, ease of use, and advantages compared with our liquid reagent set. We
      tested 42 samples from blood (n = 15), bone marrow (n = 17), and tissue (n = 10)
      with the combination CD4/CD8/KAPPA/LAMBDA/CD19/CD56/CD5/CD20/CD10/CD3/CD45 and a
      vital dye by both methods and compared positivity and staining intensity for each
      antigen. Of the 42 samples, 5 were normal samples, 3 were red cell disorders, 20
      were B-cell malignancies, 5 T-cell malignancies, 4 myeloid malignancies, and the
      remaining 5 were other diagnoses. Dried reagents gave equivalent staining
      intensity results to our standard panel in a variety of sample types, with
      diagnoses including reactive lymphocytosis, chronic lymphocytic leukemia, and
      various lymphomas. Our standard panel for evaluation of mature lymphoid
      malignancies allows rapid assessment of any sample type while providing direct
      assessment of viability. The dried reagent tube reduces preanalytical work, with
      simple addition of sample and the viability dye to the tube, saving time,
      reducing potential errors, and obviating need to titrate and monitor individual
      antibodies. With a shelf life of at least 12 months, the reagents also offer
      potential savings in reagent costs by reducing wastage due to expiration or
      tandem breakdown in standard liquid formulation.

PMID- 25944190
TI  - Nuclear cardiology: role in the world of multimodality cardiac imaging.

PMID- 25944191
TI  - Implantation of the Subcutaneous Implantable Defibrillator S-ICD(TM): Initial
      Experience in a Single Spanish Center.

PMID- 25944192
TI  - The Use of Coronary Artery Bypass Graft in our Setting. Are We Following the
      Recommendations of the Clinical Guidelines?

PMID- 25944193
TI  - Good hospitals.

PMID- 25944194
TI  - What counts as equipoise?

PMID- 25944195
TI  - Muddled measures of risks and misremembered reasons.

PMID- 25944196
TI  - The author replies.

PMID- 25944197
TI  - The potential harms and benefits from research on medical practices.

PMID- 25944198
TI  - In memoriam: Alan Wertheimer.

PMID- 25944199
TI  - Discharge decisions and the dignity of risk.

PMID- 25944200
TI  - "Right to Try" Laws: The Gap between Experts and Advocates.

PMID- 25944201
TI  - "Aid in dying" in the courts.

PMID- 25944202
TI  - Case study. Consultations across Languages. Commentary.

PMID- 25944203
TI  - Graphic medicine: comics turn a critical eye on health care.

PMID- 25944204
TI  - Graphic medicine in the university.

PMID- 25944205
TI  - Ethics of development assistance for health.

PMID- 25944206
TI  - Backward by Design: Building ELSI into a Stem Cell Science Curriculum.

PMID- 25944207
TI  - Must we be courageous?
AB  - Courage is indispensable. Telling caregivers they must be courageous in difficult
      circumstances is sometimes a back-handed endorsement of oppression, however.

PMID- 25944208
TI  - Practitioner courage and ethical health care environments.

PMID- 25944210
TI  - Incentives for healthy behavior.

PMID- 25944211
TI  - Field notes. The light that endures. Remembering John Arras.

PMID- 25944212
TI  - A mobile phone and web-based intervention for improving mental well-being in
      young people with type 1 diabetes: design of a randomized controlled trial.
AB  - BACKGROUND: Young people with type 1 diabetes experience elevated levels of
      emotional distress that impact negatively on their diabetes self-care, quality of
      life, and disease-related morbidity and mortality. While the need is great and
      clinically significant, a range of structural (eg, service availability),
      psychological (eg, perceived stigma), and practical (eg, time and lifestyle)
      barriers mean that a majority of young people do not access the support they need
      to manage the emotional and behavioral challenges of type 1 diabetes. OBJECTIVE:
      The aim of this study is to examine the effectiveness of a fully-automated
      cognitive behavior therapy-based mobile phone and Web-based psychotherapeutic
      intervention (myCompass) for reducing mental health symptoms and diabetes-related
      distress, and improving positive well-being in this vulnerable patient group.
      METHODS: A two-arm randomized controlled trial will be conducted. Young people
      with type 1 diabetes and at least mild psychological distress will be recruited
      via outpatient diabetes centers at three tertiary hospitals in Sydney, Australia,
      and referred for screening to a study-specific website. Data will be collected
      entirely online. Participants randomized to the intervention group will use the
      myCompass intervention for 7 weeks, while at the same time a control group will
      use an active placebo program matched to the intervention on duration, mode of
      delivery, and interactivity. RESULTS: The primary outcome will be mental well
      being (ie, depression, anxiety, diabetes-related distress, and positive well
      being), for which data will be collected at baseline, post-intervention, and
      after 3 months follow-up. Secondary outcomes will be functional (work and social
      functioning and diabetes self-care), biochemical measures (HbA1c), and mental
      health self-efficacy. We aim to recruit 280 people into the study that will be
      conducted entirely online. Group differences will be analyzed on an intention-to
      treat basis using mixed models repeated measures. CONCLUSIONS: We hypothesize
      that scores on the outcome measures will improve significantly for young people
      who use the mobile phone and Web-based intervention compared to the control
      group. myCompass is a public health intervention that is broadly available and
      free to use. If effective, the program has the capacity to provide convenient and
      accessible evidenced-based care to the large group of young people with type 1
      diabetes who do not currently access the psychosocial support they need. TRIAL
      REGISTRATION: Australian New Zealand Clinical Trials Registry:
      ACTRN12614000974606;
      https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366607 (Archived
      by WebCite at http://www.webcitation.org/6YGdeT0Dk).

PMID- 25944214
TI  - Overweight and Pediatric Inflammatory Disease: Is It a True Association?

PMID- 25944213
TI  - Role of Coping With Symptoms in Depression and Disability: Comparison Between
      Inflammatory Bowel Disease and Abdominal Pain.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) and abdominal pain of functional
      origin (AP) are common gastrointestinal disorders in children, which are
      associated with increased risk for depression and disability. Both symptom
      severity and coping with symptoms may contribute to these outcomes. We
      hypothesized that children with AP use different coping strategies compared with
      those with IBD for a number of reasons, including the fact that fewer treatment
      options are available to them. We also examined whether coping was related to
      depression and functional disability beyond the contributions of symptom
      severity. METHODS: The study method included secondary data analysis of 2
      existing data sets including 200 children with AP (73% girls, mean age 11.2
      years) and 189 children with IBD (49% girls, mean age 13.8 years). RESULTS:
      Compared with patients with IBD, patients with AP reported more use of coping
      strategies of self-isolation, behavioral disengagement, and catastrophizing, as
      well as problem solving and seeking social support. Multivariate analyses
      revealed that, in both samples, >=1 coping strategies were associated with
      depression and functional disability, independent of symptom severity, and
      controlling for age and sex. In IBD, symptoms were not a significant predictor of
      depression but coping was. Catastrophizing predicted depression and disability in
      both samples. CONCLUSIONS: Patients with AP report more frequent use of several
      of the coping strategies we measured compared with patients with IBD. Certain
      types of coping, particularly catastrophizing, were associated with greater
      depression and functional disability in both groups. Clinicians should be aware
      of maladaptive coping, which may be a risk factor for poor psychosocial and
      functional outcomes in both patient groups.

PMID- 25944215
TI  - Authors' Response.

PMID- 25944217
TI  - Genetic Polymorphisms in Autophagy-Associated Genes in Korean Children With Early
      Onset Crohn Disease.
AB  - OBJECTIVE: The aim of the present study was to investigate the genetic
      polymorphisms of the autophagy-associated genes autophagy-related 16-like 1
      (ATG16L1), immunity-related GTPase M (IRGM), Unc-51-like kinase 1 (ULK1), and
      NOD2 with respect to early-onset Crohn disease (CD) among Korean children.
      METHODS: A total of 65 patients with CD from the Seoul National University
      Children's Hospital, from January 2000 to May 2012, and 72 unaffected controls
      were selected. Twelve different single nucleotide polymorphisms (SNPs) were
      analyzed (TaqMan assay: ATG16L1 rs2241880, IRGM SNPs [rs13361189, rs4958847,
      rs1000113, rs10065172, and rs72553867], ULK1 SNPs [rs12303764, rs10902469, and
      rs7488085], NOD2 SNPs [Arg702Trp and Gly908Arg]; direct sequencing: NOD2
      leu1007fsinsC). The onset age of patients was 8.6 +/- 4.7 years. Twelve patients
      (18.5%) had an onset age of <1 year. RESULTS: Two of the 12 SNPs showed
      significant results. IRGM rs1000113 exhibited an association with CD with respect
      to its minor allele frequency (odds ratio [OR] 1.71, 95% confidence interval [CI]
      1.05-2.79, P = 0.03) and genotype distribution (dominant model: OR 2.17, 95% CI
      1.07-4.39, P = 0.03). IRGM rs72553867 exhibited association with CD with respect
      to its minor allele frequency (OR 0.50, 95% CI 0.27-0.91, P = 0.02) and genotype
      distribution (dominant model: OR 0.50, 95% CI 0.23-0.94, P = 0.03). The 3 SNPs of
      NOD2 existed only as wild types for both groups. In the genotype-phenotype
      analysis, the onset age, disease location, and disease behavior exhibited no
      association. CONCLUSIONS: IRGM rs1000113 and IRGM rs72553867 exhibited
      associations with early-onset CD as risk loci and defense loci, respectively.
      This suggests that the autophagy pathway plays an important role in early-onset
      CD.

PMID- 25944218
TI  - Influence of Enteral Nutrition on Occurrences of Necrotizing Enterocolitis in
      Very-Low-Birth-Weight Infants.
AB  - OBJECTIVE: The aim of the present study was to investigate the influence of
      enteral feeding management on occurrences of necrotizing enterocolitis (NEC) in
      very-low-birth-weight (VLBW) infants. METHODS: This was a case-control study
      conducted in a sample of 1028 VLBW infants (750 to 1499 g) admitted to a neonatal
      intensive care unit between January 2003 and May 2008. "Cases" were infants born
      with VLBW and diagnosed with NEC within the first 30 days of life, and "controls"
      were VLBW infants who did not develop NEC during this period. Occurrences of NEC
      were defined using the modified Bell criteria (stage >=2). RESULTS: Among the
      1028 VLBW infants, 55 (5.4%) developed NEC within the first month of life.
      Logistic regression analysis showed that breast milk given exclusively for <7
      days (odds ratio [OR] = 4.02), never achieving full enteral feeding during the
      first month (OR = 3.50), and parenteral nutrition (OR = 2.70) were factors that
      increased the chances of NEC occurrence. The use of vasoactive drugs was
      associated with a lower risk of NEC (OR = 0.15). CONCLUSIONS: Breast milk should
      be recommended as a priority for the enteral nutrition of VLBW infants for no <7
      days. Enteral nutrition should start early and progress quickly to achieve full
      enteral feeding; these procedures may help reduce the occurrence of NEC.

PMID- 25944219
TI  - Adherence to Endoscopy Biopsy Guidelines for Celiac Disease.
AB  - OBJECTIVE: Histologic changes in celiac disease (CD) may be patchy or confined to
      the bulb. Present guidelines recommend obtaining multiple biopsies from the bulb
      and distal duodenum when evaluating for CD. Adherence to these recommendations
      among adult gastroenterologists is low. There are no such data for pediatric
      gastroenterologists. This study compared endoscopic biopsy practices among
      pediatric gastroenterologists in histologically confirmed patients with CD to
      those without histologically confirmed CD. METHODS: Retrospective review of
      esophagogastroduodenoscopies (EGDs) during a 13-month period was performed.
      Children with histologically confirmed CD and a random sample of age-matched
      children without CD were identified. Endoscopy and histology reports were
      reviewed. The site and number of biopsy samples obtained was recorded. The groups
      were compared for number of biopsies. RESULTS: A total of 98 children with CD
      were compared with 103 controls without CD. The number of biopsies obtained in
      the group with CD was higher than the group without CD (5.9 +/- 1.6 vs 3.6 +/-
      1.2) (P < 0.0001). In children with CD, 80.5% had >=5 biopsies compared with
      11.7% in the group without CD (P < 0.0001). Only 10% of the children in the group
      with CD had bulb biopsies documented compared with none in the group without CD.
      CONCLUSIONS: Pediatric gastroenterologists at our center generally obtain the
      recommended number of biopsies in children with histologically confirmed CD but
      seldom document biopsies from the bulb. In those without histologic evidence of
      CD, fewer biopsies are obtained with none documented from the bulb. Failure to
      take the recommended number of biopsies could result in some missed cases of CD.

PMID- 25944220
TI  - Pulmonary Hemosiderosis Associated With Celiac Disease: Lane Hamilton Syndrome.

PMID- 25944221
TI  - Training in Video Capsule Endoscopy: A Call for Curriculum Development.

PMID- 25944222
TI  - The potential of sestrins as therapeutic targets for diabetes.
AB  - Sestrins (Sesn1/2/3) belong to a small protein family that has versatile
      biological functions. In addition to initially characterized oxidoreductase
      activity, sestrins also have oxidoreductase-independent functions, including
      activation of AMP-activated protein kinase, inhibition of the mechanistic target
      of rapamycin complex 1 (mTORC1) and activation of mTORC2. As these kinases are
      important for metabolic regulation, sestrins have a favorable profile as
      potential therapeutic targets for metabolic diseases such as diabetes. Recent
      data are in line with such a notion. In this editorial, I have attempted to
      provide a brief update on the major findings in regard to sestrins in metabolism.

PMID- 25944223
TI  - A Tale of Two Hyper-diversities: Diversification dynamics of the two largest
      families of lichenized fungi.
AB  - Renewed interests in macroevolutionary dynamics have led to the proliferation of
      studies on diversification processes in large taxonomic groups, such as
      angiosperms, mammals, and birds. However, such a study has yet to be conducted in
      lichenized fungi--an extremely successful and diverse group of fungi. Analysing
      the most comprehensive time-calibrated phylogenies with a new analytical method,
      we illustrated drastically different diversification dynamics between two hyper
      diverse families of lichenized fungi, Graphidaceae and Parmeliaceae, which
      represent more than a fourth of the total species diversity of lichenized fungi.
      Despite adopting a similar nutrition mode and having a similar number of species,
      Graphidaceae exhibited a lower speciation rate, while Parmeliaceae showed a sharp
      increase in speciation rate that corresponded with the aridification during the
      Oligocene-Miocene transition, suggesting their adaptive radiation into a novel
      arid habitat.

PMID- 25944224
TI  - Tau co-organizes dynamic microtubule and actin networks.
AB  - The crosstalk between microtubules and actin is essential for cellular functions.
      However, mechanisms underlying the microtubule-actin organization by cross
      linkers remain largely unexplored. Here, we report that tau, a neuronal
      microtubule-associated protein, binds to microtubules and actin simultaneously,
      promoting in vitro co-organization and coupled growth of both networks. By
      developing an original assay to visualize concomitant microtubule and actin
      assembly, we show that tau can induce guided polymerization of actin filaments
      along microtubule tracks and growth of single microtubules along actin filament
      bundles. Importantly, tau mediates microtubule-actin co-alignment without
      changing polymer growth properties. Mutagenesis studies further reveal that at
      least two of the four tau repeated motifs, primarily identified as tubulin
      binding sites, are required to connect microtubules and actin. Tau thus
      represents a molecular linker between microtubule and actin networks, enabling a
      coordination of the two cytoskeletons that might be essential in various neuronal
      contexts. 

PMID- 25944226
TI  - Intimal arteritis in renal allografts: new takes on an old lesion.
AB  - PURPOSE OF REVIEW: Inflammation of the arterial wall has been recognized as a key
      element of rejection since the early studies of pathologic changes in
      transplanted organs. Better elucidation of the mechanisms involved in endothelial
      injury has brought increasing complexity to the diagnostic classification of this
      lesion in the context of transplantation, and has affected the clinical
      management of patients with allograft rejection. Here, we examine how our
      understanding of the significance of intimal arteritis in renal graft biopsies
      has evolved in the past decades. RECENT FINDINGS: Recognition that antidonor
      antibody may cause intimal arteritis has prompted revision of histologic
      classifications of transplant rejection. Although molecular signatures/biomarkers
      are being developed and proposed as new tools for aiding in the identification of
      cell-mediated and antibody-mediated types of rejection, histological examination
      is still needed to identify intimal arteritis in allograft biopsies. Outcome
      studies are contributing to clarify the prognostic significance of intimal
      arteritis in transplant rejection. SUMMARY: Intimal arteritis remains an
      important histologic feature of allograft rejection, which comes in different
      nuances requiring tailored therapeutic approaches.

PMID- 25944225
TI  - Time-varying coefficients in a multivariate frailty model: Application to breast
      cancer recurrences of several types and death.
AB  - During their follow-up, patients with cancer can experience several types of
      recurrent events and can also die. Over the last decades, several joint models
      have been proposed to deal with recurrent events with dependent terminal event.
      Most of them require the proportional hazard assumption. In the case of long
      follow-up, this assumption could be violated. We propose a joint frailty model
      for two types of recurrent events and a dependent terminal event to account for
      potential dependencies between events with potentially time-varying coefficients.
      For that, regression splines are used to model the time-varying coefficients.
      Baseline hazard functions (BHF) are estimated with piecewise constant functions
      or with cubic M-Splines functions. The maximum likelihood estimation method
      provides parameter estimates. Likelihood ratio tests are performed to test the
      time dependency and the statistical association of the covariates. This model was
      driven by breast cancer data where the maximum follow-up was close to 20 years. 

PMID- 25944227
TI  - Intestinal preservation for transplantation: current status and alternatives for
      the future.
AB  - PURPOSE OF REVIEW: Among transplantable abdominal organs the intestine has the
      shortest cold storage time, raising significant medical and logistical
      challenges. Herein, established and innovative, emerging concepts in intestinal
      preservation are summarized. RECENT FINDINGS: The method of intestinal
      preservation using an in-situ vascular perfusion followed by static storage
      remained unchanged for almost 30 years, despite suboptimal results. Advanced
      preservation injury occurs within 12 h and is little influenced by the type of
      solution used. Recent reports indicate that several customized luminal solutions
      containing various amino acids and macromolecules may delay its development. In
      addition, gaseous interventions in the storage solutions or in the lumen seem
      promising and easily applicable tools that may further reduce the ischemia
      reperfusion injury and safely prolong the preservation time. Rodent models are
      not entirely suitable for direct translation to clinical practice as the
      development of preservation injury is faster than in humans. SUMMARY: The
      limitations of intestinal preservation originate in the methods (vascular
      perfusion and static storage) rather than in the solutions used. Several
      additional strategies promise to prolong the cold storage and reduce its impact
      on the intestinal graft and deserve further exploration in large animals and
      clinical studies.

PMID- 25944228
TI  - Fungal infections in intestinal and multivisceral transplant recipients.
AB  - PURPOSE OF REVIEW: Patients who undergo intestinal and multivisceral
      transplantation are at increased risk for infectious complications. Fungal
      infections are major causes of morbidity and mortality in these patients. The
      current review highlights key diagnostic and management issues in this
      population. RECENT FINDINGS: Invasive infections caused by Candida spp. remain
      the most common invasive fungal infections in intestinal and multivisceral
      transplant recipients. Aspergillus is an emerging pathogen but data are limited
      to case reports or case series. Other fungi including the mucorales, Cryptococcus
      and endemic mycoses are emerging pathogens but data regarding incidence and
      timing of disease in intestinal and multivisceral transplant recipients are
      lacking. SUMMARY: Invasive candidiasis is the most common fungal infection in
      patients with intestinal and multivisceral transplants. Experience for diagnosis
      and management comes from case series and single centers. Diagnosis and
      management of infections caused by other pathogens such as Aspergillus,
      Cryptococcus, Mucor, and endemic mycoses is usually extrapolated from other solid
      organ transplant recipients.

PMID- 25944229
TI  - The role of electron microscopy in renal allograft biopsy evaluation.
AB  - PURPOSE OF REVIEW: To review and discuss the use of electron microscopy in the
      examination of renal transplant biopsies, in particular its role in the diagnosis
      of glomerular disease and antibody-mediated rejection. RECENT FINDINGS: Electron
      microscopy can detect recurrent and de-novo glomerular disease at early stages,
      in particular for focal and segmental glomerulosclerosis and thrombotic
      microangiopathy.Ultrastructural features are an integral part of the Banff
      definition of chronic, active antibody-mediated rejection, which has been
      recently modified to include ultrastructural-only glomerular double contours. In
      addition, the threshold of peritubular capillary basement membrane multilayering
      diagnostic for chronic, active antibody-mediated rejection has been changed. As
      an area for further investigation, ultrastructural-only glomerular and
      peritubular capillary features could become tools in the early detection of
      antibody-mediated rejection. SUMMARY: Electron microscopy is important in the
      diagnosis of glomerular disease and chronic, active antibody-mediated rejection,
      both of which contribute to late graft loss. Early detection and treatment may
      help prolong graft survival. More data are needed on the early ultrastructural
      features of antibody-mediated injury, so that the usefulness of this technique
      can be compared with emerging technologies such as transcript analysis.

PMID- 25944230
TI  - T-cell-mediated rejection of the kidney in the era of donor-specific antibodies:
      diagnostic challenges and clinical significance.
AB  - PURPOSE OF REVIEW: Burgeoning literature on antibody-mediated rejection (ABMR)
      has led to a perception that T-cell-mediated rejection (TCMR) is no longer a
      significant problem. This premise needs to be carefully appraised. RECENT
      FINDINGS: A review of the literature indicates that TCMR remains an independent
      risk factor for graft loss. Importantly, it can occur as a sensitizing event that
      triggers ABMR, and adversely affects its outcome. Moreover, T cells are regularly
      present in lesions used to diagnose ABMR, and these lesions can also develop in
      the absence of donor-specific antibodies (DSA). Conversely, patients with DSA are
      at risk for mixed ABMR-TCMR, which is quite common in many studies, and may
      require a combined anti-T-cell and anti-B-cell strategy for the best outcome.
      SUMMARY: T-cell-based clinical monitoring and therapy is still relevant for
      prophylaxis of both cellular and humoral rejection, treatment of steroid
      refractory TCMR, which occurs in up to 20% of patients, and optimization of
      clinical outcome in mixed TCMR-ABMR, which is more frequently encountered than
      generally appreciated, and still associated with unacceptably high rates of graft
      loss.

PMID- 25944232
TI  - Current knowledge on regulation and impairment of motility after intestinal
      transplantation.
AB  - PURPOSE OF REVIEW: Understanding the key mechanisms impacting on intestinal graft
      motility is paramount for successful intestinal transplantation. In this review,
      we will discuss causes of graft hypomotility and hypermotility, rooted in changes
      of the intrinsic nervous system, local inflammatory processes, adaptive immune
      responses, and more. RECENT FINDINGS: Recently, it has been shown that the gut
      microbiome closely interacts with the structural integrity and rejection
      processes in the small intestine. After the ischemia/reperfusion injury is
      overcome, the absence of rejection is important to maintain graft motor function.
      The interstitial cells of Cajal, with their pacemaker function, play an important
      role by regulating propulsive intestinal motility in the initial absence of
      extrinsic signaling. Local inflammatory and immunological changes in the tunica
      muscularis of transplanted intestines also result in dysmotility, both after
      ischemia/reperfusion and during rejection. SUMMARY: Motility of the transplanted
      intestine is crucial for transplant outcome and depends on multiple factors.
      Extrinsic denervation and changes in the intrinsic intestinal nervous system,
      local inflammation in the tunica muscularis, acute and chronic rejection, changes
      in the microbiome with Toll-like receptor activation, stasis of intestinal
      contents with bacterial translocation, all multifactorially result in impaired
      graft motility. These factors must be individually acknowledged and addressed to
      obtain adequate graft function.

PMID- 25944233
TI  - Current understanding of alloimmunity of the intestinal graft.
AB  - PURPOSE OF REVIEW: This review focuses on the known mechanisms of alloimmunity
      that occur after transplantation and what is being done in order to improve graft
      and patient survival, particularly in the long term. RECENT FINDINGS: The
      presence of mismatched antigens and epitopes might relate directly to the
      development of de-novo donor-specific antibodies (DSA), and thus, rejection. In
      an abdominal wall transplant, the skin graft could be the first to show signs of
      rejection. The epithelial or endothelial cells are the main targets in acute and
      chronic rejection, respectively. Possible therapeutical targets are gut homing T
      cells and cells of the innate immune system. Chimerism development might mostly
      occur in isolated lymph nodes, but also in the epithelium, particularly after
      transplantation of bone marrow mesenchymal stromal cells. SUMMARY: Ischemia
      reperfusion, surgical injury, and bacterial translocation trigger the innate
      immune system, starting acute rejection. Interaction between donor and recipient
      immune cells generate injury and tolerance, which occur mostly in secondary
      lymphoid organs, lamina propria, and epithelium. Chronic rejection mostly affects
      the endothelial cells, generating graft dysfunction. DSA increase the risk of
      graft rejection both acutely and chronically, and the liver protects against
      their effects. Induction therapies deplete lymphocytes prior to implantation, and
      maintenance therapies inhibit T-cell expansion. Rejection rates are the lowest
      when depleting drugs and a combination of interleukin 2 receptor blockade,
      inhibition of T-cell expansion, and steroids are used as maintenance therapy.
      Chimerism and tolerogenic regiments that induce Tregs and prevent the development
      of DSA are important treatment goals for the future.

PMID- 25944231
TI  - ABO-compatible liver allograft antibody-mediated rejection: an update.
AB  - PURPOSE OF REVIEW: Liver allograft antibody-mediated rejection (AMR) studies have
      lagged behind parallel efforts in kidney and heart because of a comparative
      inherent hepatic resistance to AMR. Three developments, however, have increased
      interest: first, solid phase antibody testing enabled more precise antibody
      characterization; second, increased expectations for long-term, morbidity-free
      survival; and third, immunosuppression minimization trials. RECENT FINDINGS: Two
      overlapping liver allograft AMR phenotypic expressions are beginning to emerge:
      acute and chronic AMR. Acute AMR usually occurs within the several weeks after
      transplantation and characterized clinically by donor-specific antibodies (DSA)
      persistence, allograft dysfunction, thrombocytopenia, and hypocomplementemia.
      Acute AMR appears histopathologically similar to acute AMR in other organs:
      diffuse microvascular endothelial cell hypertrophy, C4d deposits, neutrophilic,
      eosinophilic, and macrophag-mediated microvasculitis/capillaritis, along with
      liver-specific ductular reaction, centrilobular hepatocyte swelling, and
      hepatocanalicular cholestasis often combined with T-cell-mediated rejection
      (TCMR). Chronic AMR is less well defined, but strongly linked to serum class II
      DSA and associated with late-onset acute TCMR, fibrosis, chronic rejection, and
      decreased survival. Unlike acute AMR, chronic AMR is a slowly evolving insult
      with a number of potential manifestations, but most commonly appears as low-grade
      lymphoplasmacytic portal and perivenular inflammation accompanied by unusual
      fibrosis patterns and variable microvascular C4d deposition; capillaritis can be
      more difficult to identify than in acute AMR. SUMMARY: More precise DSA
      characterization, increasing expectations for long-term survival, and
      immunosuppression weaning precipitated a re-emergence of liver allograft AMR
      interest. Pathophysiological similarities exist between heart, kidney, and liver
      allografts, but liver-specific considerations may prove critical to our ultimate
      understanding of all solid organ AMR.

PMID- 25944234
TI  - Hepatitis C treatment for patients post liver transplant.
AB  - PURPOSE OF REVIEW: To give a comprehensive update of the current hepatitis C
      (HCV) antiviral treatments in the liver transplant setting. RECENT FINDINGS:
      Hepatitis C treatment after liver transplantation with several interferon-free
      combinations has shown excellent efficacy and safety results, overwhelming
      interferon-based therapies in this setting. In posttransplant decompensated liver
      disease, however, efficacy of antiviral therapies seems to be lower, but viral
      eradication has been associated with an improvement of liver function and
      clinical status in most cases. Hence, antiviral treatment should be offered
      before advanced liver disease is reached, in order to prevent graft damage and
      guarantee the best efficacy rates of therapies. SUMMARY: New interferon-free
      combinations with potent direct antivirals cure hepatitis C in most of patients
      after liver transplantation. Hepatitis C after liver transplantation should be
      treated as early as possible and before advanced liver disease is established in
      the graft. In patients with graft cirrhosis, eradication of hepatitis C is
      associated with improved liver function.

PMID- 25944235
TI  - The molecular phenotypes of rejection in kidney transplant biopsies.
AB  - PURPOSE OF REVIEW: The recent emergence of a system for distinguishing T-cell
      mediated rejection (TCMR) from antibody-mediated rejection (ABMR), including C4d
      negative ABMR, allows us to map the molecular features of these conditions.
      RECENT FINDINGS: The TCMR landscape is dominated by molecules expressed in
      effector T cells, antigen-presenting cells (macrophages, dendritic cells, B
      cells) and interferon-gamma (IFNG)-induced genes. A surprising finding is the
      association of transcripts for inhibitory molecules such as CTLA4 and PDL1 with
      TCMR, indicating that this tubulo-interstitial inflammatory compartment is
      actively controlled. ABMR is dominated by endothelial transcripts related to
      angiogenesis, reflecting endothelial injury; natural killer (NK)-cell
      transcripts; and selected IFNG-regulated transcripts. This suggests a cognate
      unit of NK cells engaging donor-specific antibody bound to donor human leukocyte
      antigen antigens through their CD16a (FCGR3A) Fc receptors, triggering IFNG
      release. TCMR and ABMR share many rejection-associated transcripts, mainly IFNG
      induced genes and transcripts shared between NK cells and CD8 effector T cells
      (e.g., KLRD1). In addition, acute kidney injury transcripts, which reflect the
      parenchymal response to injury, are shared between different forms of rejection
      and are indicative of disease progression. SUMMARY: Microarray assessment
      provides a new dimension in biopsy assessment for diagnosis that offers
      mechanistic insights and sometimes challenges histology assessments.

PMID- 25944236
TI  - Reappraisal of the hepatitis C virus-positive donor in solid organ
      transplantation.
AB  - PURPOSE OF REVIEW: Hepatitis C virus (HCV)-positive donor allografts may be
      considered for HCV-positive recipients, but are underutilized. With new effective
      antiviral treatments, we aim to review data on the use of HCV-positive allografts
      in solid organ transplantation and place them in the context of the changing HCV
      landscape. RECENT FINDINGS: Hepatitis C is the most common indication for liver
      transplant in the USA and Europe and a significant comorbidity in patients on the
      waitlist for nonliver solid organ transplantation. Patients with HCV on the
      waitlist for nonliver solid organ transplantation have worse outcomes compared
      with those without HCV. However, survival after transplantation is improved
      compared with those who remain on the waitlist. There has been concern that use
      of HCV-positive allografts would lead to worse post-transplant outcomes. However,
      more recent data suggest that transplant outcomes for recipients who accept HCV
      positive donor allografts may be comparable with those who receive HCV-negative
      allografts. Emerging treatments to eradicate HCV have further improved the course
      of HCV-positive individuals, with improved efficacy and reduced side-effects.
      SUMMARY: In view of the changing landscape of hepatitis C treatment and reduced
      wait time on the transplant waiting lists for those accepting HCV-positive
      donors, future use of select HCV-positive donors in solid organ transplantation
      should be encouraged.

PMID- 25944237
TI  - Hepatitis C virus infection in nonliver solid organ transplant candidates and
      recipients.
AB  - PURPOSE OF REVIEW: Transplantation is the best treatment for many patients with
      end-stage organ failure. Hepatitis C infection is prevalent among solid organ
      candidates and recipients and continues to represent a major source of morbidity
      and mortality. Prior interferon (IFN)-based therapies have been associated with
      limited efficacy and high rates of adverse events. Furthermore, prior IFN-based
      regimens are associated with high rates of allograft rejection limiting their use
      post-transplant. This review will outline the limited experience with current
      treatment regimens and how to incorporate the new hepatitis C virus (HCV)
      treatment regimens. RECENT FINDINGS: The introduction of new direct-acting
      antiviral (DAA) agents against HCV has dramatically altered the landscape of
      treatment for HCV. Different all-oral regimens are currently available and are
      rapidly becoming the standard for treating patients with chronic hepatitis C.
      Excluding patients with liver disease or those who received liver transplant,
      those regimens have not been studied in patients awaiting solid organ transplant,
      or those transplanted. SUMMARY: The safety and efficacy of DAAs in patients
      awaiting liver transplant and liver transplant recipients provide us with some
      insight and guidance on how to use those all-oral IFN-free regimens to allow
      effective treatment for patients who received or are awaiting nonliver solid
      organ transplants.

PMID- 25944238
TI  - New hepatitis C virus therapies: drug classes and metabolism, drug interactions
      relevant in the transplant settings, drug options in decompensated cirrhosis, and
      drug options in end-stage renal disease.
AB  - PURPOSE OF REVIEW: This article will review the new direct acting antiviral agent
      (DAA) drug classes for the treatment of hepatitis C, how they are combined and
      the relevant drug-drug interactions in the postliver transplant setting.
      Treatment options for chronic hepatitis C in patients with decompensated
      cirrhosis and end-stage renal disease will also be discussed. RECENT FINDINGS:
      The availability of new drug classes has increased the treatment options in
      patients with hepatitis C in the post-transplant settings. Clinical trials have
      concluded that sofosbuvir (SOF) with ledipasvir (LDV) may be safely administered
      with calcineurin inhibitors (tacrolimus, cyclosporine) and rapamycin inhibitors
      (sirolimus, everolimus). Similarly, paritaprevir/ritonavir, ombitasvir, and
      dasabuvir may be administered with tacrolimus and cyclosporine though appropriate
      dose adjustments must be made to the calcineurin inhibitors. In those with
      decompensated Childs B/C cirrhosis, SOF, SOF and LDV, as well as daclatasvir may
      be given without dose adjustment. In renal impairment, all DAAs may be used
      safely down to a glomerular filteration rate (GFR) of 30 ml/min. Simeprevir,
      paritaprevir, ombitasvir, and dasabuvir may be given for those down to GFR of 15
      ml/min. Finally, daclatasvir may be given without dose administration change.
      SUMMARY: In summary, DAAs have better tolerability and greater efficacy than
      interferon-based therapy post-transplant. Drug-drug interactions must be
      carefully assessed when these newer agents are used for therapy in the postliver
      transplant settings. Thus far, dose adjustments for DAAs have not been required
      in chronic kidney disease though data are incomplete in those with severe chronic
      kidney disease (CKD) or on dialysis. Hepatitis C treatment in those with
      decompensated cirrhosis results in impaired hepatic metabolism that may affect
      DAA levels, and clinicians should carefully choose treatment options for Childs B
      and C cirrhotic patients.

PMID- 25944239
TI  - Hepatitis C treatment in patients on the liver transplant waiting list.
AB  - PURPOSE OF REVIEW: Hepatitis C virus (HCV) infection remains the leading
      indication for liver transplant, and viral eradication prior to liver transplant
      to prevent disease recurrence has traditionally been challenging because of the
      poor tolerability and efficacy of available therapies. However, with the recent
      introduction of potent interferon (IFN)-free direct acting antiviral regimens,
      viral eradication prior to liver transplant is now possible. RECENT FINDINGS:
      Although data are limited, several proof of concept studies have now shown high
      rates of safety and efficacy in patients with compensated as well as mild-to
      moderately decompensated cirrhosis. Although, treatment on the liver transplant
      waiting list can safely prevent postliver transplant recurrence in selected
      patients, the ideal regimen and treatment duration have yet to be determined.
      SUMMARY: Although IFN-free therapies represent a tremendous advance in our
      ability to cure this previously difficult to treat population, additional data on
      the safety of these regimens, particularly in patients with severely
      decompensated cirrhosis, the consequences of virologic failure and the impact of
      viral eradication on short- and long-term liver function are urgently needed.

PMID- 25944241
TI  - Correlates of partner support to abstain from prenatal alcohol use: a cross
      sectional survey among Dutch partners of pregnant women.
AB  - Partners can play an important role, but are often ignored in interventions
      targeting the prevention of prenatal alcohol use. A better understanding of the
      correlates of partner support to abstain from prenatal alcohol use can help to
      make a better use of partner support. The aim of this study was to identify
      correlates of this support by analysing differences between partners reporting
      low versus high support. An online cross-sectional study among 237 Dutch partners
      of pregnant women was conducted. Respondents were recruited through Dutch
      midwifery practices in September-October 2009. Questionnaires were based on the I
      Change Model. Chi-square and t-test showed that partners reporting high support
      were more likely to desire their partner to abstain from alcohol use and to have
      received advice from their pregnant spouse or midwife that abstinence was
      desirable. They also had stronger perceptions that the baby would experience harm
      from prenatal alcohol use and that harm could be more severe, and they saw more
      advantages and fewer disadvantages of providing support. They also reported more
      influence from their social environment encouraging their support, had greater
      self-efficacy and had a stronger intention to support their partner during the
      remainder of the pregnancy compared to partners reporting low support. Health
      professionals may improve their alcohol advice by discussing the advantages and
      disadvantages of support with the partner and by encouraging couples to discuss
      and propose solutions for the situations in which partners find it difficult not
      to support alcohol abstinence. By providing an insight into important correlates
      of partner support, this study expands the research area aiming to reduce
      prenatal alcohol use.

PMID- 25944240
TI  - Hepatitis C virus-HIV-coinfected patients and liver transplantation.
AB  - PURPOSE OF REVIEW: To review the experience to date and unique challenges
      associated with liver transplantation in hepatitis C virus (HCV)/HIV-coinfected
      patients. RECENT FINDINGS: The prevalence of cirrhosis and hepatocellular
      carcinoma is rising among HIV-infected individuals. With careful patient
      selection and in the absence of HCV infection, HIV-infected and HIV-uninfected
      liver transplant recipients have comparable posttransplant outcomes. However, in
      the presence of HCV infection, patient and graft survival are significantly
      poorer in HIV-infected recipients, who have a higher risk of aggressive HCV
      recurrence, acute rejection, sepsis, and multiorgan failure. Outcomes may be
      improved with careful recipient and donor selection and with the availability of
      new highly potent all-oral HCV direct acting antivirals (DAAs). Although all-oral
      DAAs have not been evaluated in HIV/HCV-coinfected transplant patients, HIV does
      not adversely impact treatment success in nontransplant populations. Therefore,
      there is great hope that HCV can be successful eradicated in HIV/HCV-coinfected
      transplant patients and will result in improved outcomes. Careful attention to
      drug-drug interactions with HIV antiretroviral agents, DAAs, and posttransplant
      immunosuppressants is required. SUMMARY: Liver transplant outcomes are poorer in
      HIV/HCV-coinfected recipients compared with those with HCV-monoinfection. The new
      HCV DAAs offer tremendous potential to improve outcomes in this challenging
      population.

PMID- 25944242
TI  - Hip reconstruction is more painful than spine fusion in children with cerebral
      palsy.
AB  - PURPOSE: Concerns about pain control in patients with cerebral palsy (CP) are
      especially anxiety provoking for parents, given the fact that spasticity,
      communication issues, and postoperative muscle spasms are significant problems
      that make pain control difficult in these patients. A better understanding of the
      magnitude and quality of the pain these patients experience after our surgical
      procedures would better prepare the patients and their families. The purpose of
      this study is to quantify the amount of postoperative pain in children with CP
      undergoing hip reconstruction and spinal fusion. Specifically, the study will
      compare pain scores and the amount of narcotics used between the two groups.
      MATERIALS AND METHODS: This is a retrospective chart review of a consecutive
      series of children with CP (GMFCS levels IV and V) over a 5-year period
      undergoing hip reconstruction (femoral osteotomy, pelvic osteotomy, or both) and
      posterior spinal fusion (PSF) at a tertiary-care pediatric hospital. The primary
      end point was the total opioid used by the patient during the hospitalization, by
      converting all forms of narcotics to morphine equivalents. The secondary end
      point was the documentation of pain with standard pain scores at standard time
      points postoperatively. Adverse effects related to pain management were
      documented for both groups. Student's t-tests were utilized to statistically
      compare differences between the groups, with significance determined at p < 0.05.
      RESULTS: Forty-two patients with CP who underwent hip reconstruction (mean age
      8.8 years) were compared to 26 patients who underwent PSF (mean age 15.4 years).
      The total opioid used, normalized by body weight and by days length of stay
      (DLOS), in the hip group was 0.49 mg morphine/kg/DLOS, compared to 0.24 for the
      spine group (p = 0.014). The mean pain score for the hip group was 1.52, compared
      to 0.72 for the spine group (p = 0.013). There were no significant differences in
      the occurrence of adverse effects related to pain management between the two
      groups. CONCLUSION: Patients with CP undergoing hip reconstruction surgery had
      significantly more pain, as exhibited by requiring more narcotics and having
      higher pain scores, than those patients undergoing PSF. The knowledge that hip
      reconstruction is more painful than PSF for patients with CP will better prepare
      families about what to expect in the postoperative period and will alert
      providers to supply better postoperative pain control in these patients. LEVEL OF
      EVIDENCE: III (case control series).

PMID- 25944243
TI  - Cell type-specific responses to salinity - the epidermal bladder cell
      transcriptome of Mesembryanthemum crystallinum.
AB  - Mesembryanthemum crystallinum (ice plant) exhibits extreme tolerance to salt.
      Epidermal bladder cells (EBCs), developing on the surface of aerial tissues and
      specialized in sodium sequestration and other protective functions, are critical
      for the plant's stress adaptation. We present the first transcriptome analysis of
      EBCs isolated from intact plants, to investigate cell type-specific responses
      during plant salt adaptation. We developed a de novo assembled, nonredundant EBC
      reference transcriptome. Using RNAseq, we compared the expression patterns of the
      EBC-specific transcriptome between control and salt-treated plants. The EBC
      reference transcriptome consists of 37 341 transcript-contigs, of which 7% showed
      significantly different expression between salt-treated and control samples. We
      identified significant changes in ion transport, metabolism related to energy
      generation and osmolyte accumulation, stress signalling, and organelle functions,
      as well as a number of lineage-specific genes of unknown function, in response to
      salt treatment. The salinity-induced EBC transcriptome includes active transcript
      clusters, refuting the view of EBCs as passive storage compartments in the whole
      plant stress response. EBC transcriptomes, differing from those of whole plants
      or leaf tissue, exemplify the importance of cell type-specific resolution in
      understanding stress adaptive mechanisms.

PMID- 25944244
TI  - Vaccines.

PMID- 25944245
TI  - Arabidopsis thaliana MCM3 single subunit of MCM2-7 complex functions as 3' to 5'
      DNA helicase.
AB  - Minichromosome maintenance 2-7 (MCM2-7) proteins are conserved eukaryotic
      replicative factors essential for the DNA replication at its initiation and
      elongation step, and act as a licensing factor. The MCM2-7 and MCM4/6/7subcomplex
      exhibit DNA helicase activity, and are therefore regarded as the replicative
      helicase. The MCM proteins have not been studied in detail in plant system. Here,
      we present the biochemical characterization of Arabidopsis thaliana MCM3 single
      subunit and show that it exhibits in vitro unwinding and ATPase activities.
      AtMCM3 shows a greater unwinding activity with 5' forked partial DNA duplex
      substrate as compared to 3' forked and non-forked substrates. ATP and magnesium
      ion are indispensable for its DNA helicase activity. Specifically, ATP and dATP
      are the preferred nucleotides for its unwinding activity. The directionality of
      the AtMCM3 has been determined to be in 3' to 5' direction. The oligomerization
      status of AtMCM3 single subunit protein indicates that it is present in different
      multimeric forms. The unraveling of the helicase activity of AtMCM3 will provide
      better insights into the plant DNA replication.

PMID- 25944246
TI  - Monitoring of kidney function in HIV-positive patients.
AB  - HIV-positive patients are at increased risk of developing chronic kidney disease.
      Although guidelines recommend regular monitoring of renal function in individuals
      living with HIV, the optimal frequency remains to be defined. In this review, we
      discuss the renal syndromes that may be identified at an earlier stage via
      routine assessment of kidney function, and provide guidance in terms of the
      frequency of monitoring, the most useful tests to perform, and their clinical
      significance. Specifically, we address whether annual monitoring of kidney
      function is appropriate for the majority of HIV-positive patients. 

PMID- 25944247
TI  - Human resources for refraction services in Central Nepal.
AB  - BACKGROUND: Uncorrected refractive error is a public health problem globally and
      in Nepal. Planning of refraction services is hampered by a paucity of data. This
      study was conducted to determine availability and distribution of human resources
      for refraction, their efficiency, the type and extent of their training; the
      current service provision of refraction services and the unmet need in human
      resources for refraction in Central Nepal. METHODS: This was a descriptive cross
      sectional study. All refraction facilities in the Central Region were identified
      through an Internet search and interviews of key informants from the professional
      bodies and parent organisations of primary eye centres. A stratified simple
      random sampling technique was used to select 50 per cent of refraction
      facilities. The selected facilities were visited for primary data collection.
      Face-to-face interviews were conducted with the managers and the refractionists
      available in the facilities using a semi-structured questionnaire. RESULTS: Data
      was collected in 29 centres. All the managers (n=29; response rate 100 per cent)
      and 50 refractionists (Response rate 65.8 per cent) were interviewed.
      Optometrists and ophthalmic assistants were the main providers of refraction
      services (n=70, 92.11 per cent). They were unevenly distributed across the
      region, highly concentrated around urban areas. The median number of refractions
      per refractionist per year was 3,600 (IQR: 2,400 - 6,000). Interviewed
      refractionists stated that clients' knowledge, attitude and practice related
      factors such as lack of awareness of the need for refraction services and/or
      availability of existing services were the major barriers to the output of
      refraction services. The total number of refractions carried out in the Central
      Region per year was 653,176. An additional 170 refractionists would be needed to
      meet the unmet need of 1,323,234 refractions. CONCLUSION: The study findings
      demand a major effort to develop appropriately trained personnel when planning
      refraction services in the Central Region and in Nepal as a whole. The equitable
      distribution of the refractionists, their community-outreach services and
      awareness raising activities should be emphasised.

PMID- 25944248
TI  - Two psychiatrists who took speaker fees from drug firm resign from Texan
      hospital.

PMID- 25944249
TI  - Occupational toxic epidermal necrolysis associated with dalbergia
      cochinchinensis: a retrospective comparative study of eight cases in China.
AB  - BACKGROUND: Occupational toxic epidermal necrolysis (TEN) related to Dalbergia
      cochinchinensis has seldom been reported in the past. Its clinical characteristic
      needs to be investigated. This study reports eight cases of such disease in
      China. METHODS: Eight patients with occupational TEN admitted from 2003 to 2012
      were retrospectively analyzed and compared with 15 patients admitted with TEN
      caused by drugs as controls. Patients all received combination therapy of
      corticosteroid and intravenous immunoglobulin. The times for bullous ceasing,
      tapering of corticosteroid, and total hospitalization were compared between the
      two groups of patients. SCORTEN, a severity-of-illness scoring system for TEN
      prognosis, was applied to evaluate clinical outcome. RESULTS: The three time
      measurements in occupational TEN were longer than those in control, and the
      differences were statistically significant (P = 0.0023, 0.026, 0.0017), which
      means the total dose of corticosteroid needed in occupational TEN was higher than
      that in the control. There were no deaths in the two groups, although expected
      deaths were 0.612 and 0.836, respectively. DISCUSSION: Occupational TEN has a
      longer progression than TEN caused by drugs, and there is more difficulty in its
      treatment. Clinicians should pay attention to this disease. However, its
      mechanism and target therapy remain unclear.

PMID- 25944250
TI  - The low-affinity complex of cytochrome c and its peroxidase.
AB  - The complex of yeast cytochrome c peroxidase and cytochrome c is a paradigm of
      the biological electron transfer (ET). Building on seven decades of research, two
      different models have been proposed to explain its functional redox activity. One
      postulates that the intermolecular ET occurs only in the dominant, high-affinity
      protein-protein orientation, while the other posits formation of an additional,
      low-affinity complex, which is much more active than the dominant one. Unlike the
      high-affinity interaction-extensively studied by X-ray crystallography and NMR
      spectroscopy-until now the binding of cytochrome c to the low-affinity site has
      not been observed directly, but inferred mainly from kinetics experiments. Here
      we report the structure of this elusive, weak protein complex and show that it
      consists of a dominant, inactive bound species and an ensemble of minor, ET
      competent protein-protein orientations, which summarily account for the
      experimentally determined value of the ET rate constant. 

PMID- 25944251
TI  - Application of two methods of calculation of solvation descriptor L to estimate
      C5 -C7 alkenes retention.
AB  - The solvation descriptor L for 59 isomers of all C5 -C7 alkenes was calculated
      using two methods based on additive contributions of particular fragments in the
      molecule by the method of Havelec and Sevcik and the method of Platts and Butina.
      These descriptors were used to estimate the gas chromatography retention of
      alkenes on squalane and polydimethylsiloxane stationary phases. The retention was
      described better by the Platts-Butina method. Modification of the Havelec-Sevcik
      method by omitting the contribution for interaction of the cis isomers led to a
      substantial improvement in the estimation ability of the model. The modified
      Havelec-Sevcik method was found to be preferable for estimation of the descriptor
      L compared to the Platts-Butina method. A more comprehensive description of the
      retention of alkenes was achieved by inclusion of an additional descriptor E.
      This model with the descriptors L and E yielded better estimation for alkenes
      compared to the model with a single descriptor. 

PMID- 25944252
TI  - Fast and scalable inference of multi-sample cancer lineages.
AB  - Somatic variants can be used as lineage markers for the phylogenetic
      reconstruction of cancer evolution. Since somatic phylogenetics is complicated by
      sample heterogeneity, novel specialized tree-building methods are required for
      cancer phylogeny reconstruction. We present LICHeE (Lineage Inference for Cancer
      Heterogeneity and Evolution), a novel method that automates the phylogenetic
      inference of cancer progression from multiple somatic samples. LICHeE uses
      variant allele frequencies of somatic single nucleotide variants obtained by deep
      sequencing to reconstruct multi-sample cell lineage trees and infer the subclonal
      composition of the samples. LICHeE is open source and available at
      http://viq854.github.io/lichee . 

PMID- 25944254
TI  - Anatomical and CT approach of the adipose tissue: application in morbid obesity.
AB  - PURPOSE: The importance and proportion of visceral adipose tissue (VAT) represent
      the best criterion to define obesity. Because VAT value is difficult to obtain in
      clinical practice, the indication for bariatric surgery is still based at present
      on Body Mass index (BMI), even though BMI is a poor predictor of obesity-related
      morbid complications. This correlation study aimed at determining a simple and
      accurate computed tomography (CT) anatomic marker, which can be easily used
      clinically, well correlated with the volume of VAT and consequently with morbid
      complications. METHODS: We studied 108 CT scans of patients presenting with
      morbid obesity. Several simplified measures (external and internal abdominal
      diameters and circumferences) were conducted on CT scan view, going through the
      fourth lumbar vertebra (L4), in addition to various vertebral measurements (area
      of the vertebra, sagittal and transversal diameters), VAT and subcutaneous
      adipose tissue (SAT). Then, we reported the simplified measures values on the
      vertebral areas, and we calculated the Bertin index. Finally, we conducted a
      correlation study between all variables to obtain accurate VAT measurements.
      RESULTS: The internal abdominal circumference and the Bertin index showed the
      best correlations with VAT in morbidly obese patients (r = 0.84 and 0.85,
      respectively). BMI and anthropometric measures were not correlated with VAT.
      CONCLUSION: CT scan study allows to simply approximate VAT value in morbidly
      obese patients. An abdominal CT scan could be part of the tests used in the
      evaluation of obese patients to base therapeutic strategies on VAT values and not
      on BMI as it is the case today.

PMID- 25944253
TI  - Applied anatomical study of the modified anconeus flap approach.
AB  - PURPOSE: Conventional surgical therapy for an intercondylar humerus fracture
      might result in multiple potential complications. Our study was conducted to
      evaluate the modified anconeus flap approach by adequately exposing the distal
      humeral articular surface, avoiding osteotomy of the olecranon and transection of
      the main part of the triceps brachial tendon from the olecranon. METHODS:
      Preparations of 20 upper limb specimens from adult cadavers were used in this
      study. We investigated the anatomical features of the distal tendon of the
      triceps brachii. Then, we designed a modified anconeus flap approach in cadaver
      specimens combined with the medial paratricipital approach, and we compared the
      extent of exposure of the distal humeral articular surface between the triceps
      reflecting anconeus pedicle approach and this modified approach. RESULTS: The
      downward neurovascular bundles supplying the anconeus were located far from the
      intramuscular tendon of the triceps brachii. In addition, the medial head of the
      triceps was continuous with the anconeus near the lateral epicondyle of the
      humerus. These anatomical properties could assist in reducing adverse events in
      surgery. The percentage of the exposed humerus distal articular surface was 42.7%
      by applying the modified anconeus flap approach combined with the medial
      paratricipital approach. The modified anconeus flap approach can overcome the
      shortcomings of osteotomy or triceps transverse and fulfill reduction and
      internal fixation of most distal humerus intercondylar fractures. CONCLUSIONS:
      The present study has demonstrated a new approach for adequately exposing the
      distal humeral articular surface during surgery for an intercondylar humerus
      fracture. With this modified approach, osteotomy of the olecranon and the
      separation or transection of the main part of the triceps brachial tendon from
      the olecranon are not necessarily required. Therefore, we suggest that this novel
      approach could be applied as the primary surgical approach in intercondylar
      humerus fracture surgeries if the surgeons are familiar with the regional
      features of distal tendon of the triceps brachii and anconeus.

PMID- 25944255
TI  - Recruitment of IL-27-Producing CD4(+) T Cells and Effect of IL-27 on Pleural
      Mesothelial Cells in Tuberculous Pleurisy.
AB  - BACKGROUND: The numbers of IL-27-producing CD4(+) T cells and the concentration
      of soluble IL-27 have been found to be increased in tuberculous pleural effusion
      (TPE). The objective of the present study was to explore the mechanism by which
      IL-27(+)CD4(+) T cells are recruited into the pleural space, and to explore the
      impact of IL-27 on pleural mesothelial cells (PMCs). METHODS: The expression
      profiles of chemokine receptor (CCR) were determined by flow cytometry. The
      chemoattractant activity of chemokines CCL20 and CCL22 for IL-27(+)CD4(+) T cells
      in vitro was observed. Effects of IL-27 on wound healing, proliferation and
      apoptosis of PMCs were also investigated. RESULTS: IL-27(+)CD4(+) T cells in TPE
      expressed high level of CCR6, medium level of CCR4, and low levels of CCR2, CCR3,
      CCR5, CCR7, CCR10, and CXCR3. Recruitment of IL-27(+)CD4(+) T cells into TPE
      could be induced by pleural CCL20 and CCL22. By activating STAT3 signaling, IL-27
      significantly improved wound healing and promoted proliferation of PMCs, and
      completely prevented apoptosis of PMCs induced by IFN-gamma. CONCLUSIONS: After
      being recruited into pleural space by CCL20 or/and CCL22, these pleural IL-27
      producing CD4(+) T cells may play important roles in tuberculosis immunity by
      affecting PMC functions.

PMID- 25944256
TI  - An Adenoviral Vector Encoding Full-Length Dectin-1 Promotes Aspergillus-Induced
      Innate Immune Response in Macrophages.
AB  - INTRODUCTION: The incidence of invasive pulmonary aspergillosis (IPA) has
      increased significantly over the last two decades. Alveolar macrophages (AMs)
      represent the first line of pulmonary host response to Aspergillus conidia.
      Recognition of conidia by AMs involves Dectin-1 (CLEC7A), which is a conserved
      structure to combine beta-glucans. The deficiency of Dectin-1 results in impaired
      fungal killing and uncontrolled growth of Aspergillus fumigatus. Thus, we
      hypothesized that high expression of Dectin-1 would enhance the host recognition
      and fungal killing. METHODS: We set out to develop an adenoviral vector encoding
      full-length Dectin-1 (Ad-Dectin-1-EGFP) and then transfect it to MH-S cells.
      Transfect cell model was verified by using real-time RT-PCR, Western blot, flow
      cytometric, and confocal microscopic assays. And also, the function of Dectin-1
      was explored by measuring cytokine release and killing ability during the course
      of A. fumigatus infection. RESULTS: We constructed a recombinant adenovirus which
      could upregulate the expression of Dectin-1 and verified that Dectin-1 was
      expressed on cell membrane. The function of Dectin-1 was also demonstrated by its
      ability in promoting the production of cytokines and increasing the killing
      ability during the course of A. fumigatus infection. CONCLUSIONS: An adenoviral
      vector was successfully applied to the production of a recombinant adenovirus
      encoding full-length Dectin-1, and also, its function in Aspergillus-induced
      innate immune response was demonstrated.

PMID- 25944257
TI  - Hyaluronic acid in knee osteoarthritis: preliminary results using a four months
      administration schedule.
AB  - AIM: To evaluate the therapeutic trajectory of intra-articular injections of
      hyaluronic acid at high concentration (2%) performed at 4-month intervals.
      METHODS: Subjects with knee osteoarthritis received, after a weekly injection of
      32 mg/2 mL hyaluronic acid for 3 weeks, a single injection of 50 mg/2.5 mL
      hyaluronic acid (not cross-linked, molecular weight 800-1200 kDa) at 4-month
      interval (4, 8 and 12 months). Clinical assessment (visual analogic scale [VAS]
      for pain at rest and during activities, Lequesne Index [LI], Knee Injury and
      Osteoarthritis Outcome Score (KOOS), and monthly non-steroidal anti-inflammatory
      drug consumption) was performed at baseline, and after 1, 4, 6, 8, 12 and 14
      months. RESULTS: In the 15 knees treated, pain decreased (baseline vs. 14 months:
      VAS at rest, 3.7 +/- 1.7 vs. 1 +/- 0.7 [P < 0.000]; VAS activities, 6.2 +/- 1.7
      vs. 2.6 +/- 1.3 [P < 0.000]) and function improved (baseline vs. 14 months: KOOS,
      51.9 +/- 15.3 vs. 70.2 +/- 13.7 [P < 0.000]; LI, 10 +/- 3.8 vs. 5.4 +/- 2.4 [P <
      0.000]) significantly. CONCLUSIONS: This schedule provides persistent positive
      results in terms of reduced pain and improved function, optimizing the protective
      properties of the hyaluronic acid used.

PMID- 25944258
TI  - Seasonal and within-canopy variation in shoot-scale resource-use efficiency trade
      offs in a Norway spruce stand.
AB  - Previous leaf-scale studies of carbon assimilation describe short-term resource
      use efficiency (RUE) trade-offs where high use efficiency of one resource
      requires low RUE of another. However, varying resource availabilities may cause
      long-term RUE trade-offs to differ from the short-term patterns. This may have
      important implications for understanding canopy-scale resource use and
      allocation. We used continuous gas exchange measurements collected at five levels
      within a Norway spruce, Picea abies (L.) karst., canopy over 3 years to assess
      seasonal differences in the interactions between shoot-scale resource
      availability (light, water and nitrogen), net photosynthesis (An ) and the use
      efficiencies of light (LUE), water (WUE) and nitrogen (NUE) for carbon
      assimilation. The continuous data set was used to develop and evaluate multiple
      regression models for predicting monthly shoot-scale An . These models showed
      that shoot-scale An was strongly dependent on light availability and was
      generally well described with simple one- or two-parameter models. WUE peaked in
      spring, NUE in summer and LUE in autumn. However, the relative importance of LUE
      for carbon assimilation increased with canopy depth at all times. Our results
      suggest that accounting for seasonal and within-canopy trade-offs may be
      important for RUE-based modelling of canopy carbon uptake.

PMID- 25944259
TI  - Leisure-Time Screen-Based Sedentary Behavior and Leukocyte Telomere Length:
      Implications for a New Leisure-Time Screen-Based Sedentary Behavior Mechanism.
AB  - The field of sedentary behavior epidemiology is emerging. Short leukocyte
      telomere length (LTL) is a hallmark characteristic of aging, but LTL is also
      associated with morbidity and mortality independent of age. To my knowledge, only
      one study has examined the association between sedentary behavior and LTL. The
      purpose of this study was to examine the association between screen-based
      sedentary behavior and LTL. Data from the 1999-2002 National Health and Nutrition
      Examination Survey were used (N=6405; age, 20-84 years). Leisure-time screen
      based sedentary behavior (television, video games, computer use) was assessed via
      questionnaire, and LTL was extracted from DNA in whole blood with the LTL assay
      performed using quantitative polymerase chain reaction. After adjustments
      (including age and physical activity), for every 1-hour increase in leisure-time
      screen-based sedentary behavior, participants had a 7% increased odds (odds
      ratio, 1.07; 95% CI, 1.00-1.13; P=.04) of having LTL in the lowest tertile (vs
      highest); leisure-time screen-based sedentary behavior was not associated with
      values in the middle (vs highest) tertile (odds ratio, 1.01; 95% CI, 0.95-1.07;
      P=.62). The results of this study revealed that greater leisure-time screen-based
      sedentary behavior is associated with shorter LTL. 

PMID- 25944260
TI  - Can HIV Be Cured and Should We Try?

PMID- 25944261
TI  - [The evaluation of the retrograde memory in the Quebec population aged: PUB-40
      and PUB-12].
AB  - Memory assessment represents an important part of the clinical
      neuropsychologist's duties in a geriatric context. In fact, in Canada, about one
      third of seniors report memory complaints, with different causes. Based on the
      underlying etiology, different components of memory may be affected in older
      adults. Nonautobiographical retrograde memory (public or semantic) is an
      important aspect of memory to assess; nevertheless, there is currently no
      reliable and standardized clinical tool to evaluate this aspect of memory in the
      elderly Quebecer population. The aims of this research were therefore: (1) to
      develop a protocol specifically aimed at assessing non-autobiographical
      retrograde memory in this population, the PUB-40; (2) to obtain reference data
      among 105 healthy subjects; and (3) to develop a short version based on the items
      which discriminated a group of 20 patients with amnestic Mild cognitive
      impairment (aMCI) from older healthy subjects. 

PMID- 25944262
TI  - Characterization and applications of Nanobodies against human procalcitonin
      selected from a novel naive Nanobody phage display library.
AB  - BACKGROUND: Nanobodies (Nbs) are single-domain antigen-binding fragments derived
      from the camelids heavy-chain only antibodies (HCAbs). Their unique advantageous
      properties make Nbs highly attractive in various applications. The general
      approach to obtain Nbs is to isolate them from immune libraries by phage display
      technology. However, it is unfeasible when the antigens are toxic, lethal,
      transmissible or of low immunogenicity. Naive libraries could be an alternative
      way to solve the above problems. RESULTS: We constructed a large camel naive
      phage display Nanobody (Nb) library with great diversity. The generated library
      contains to 6.86 * 10(11) clones and to our best of knowledge, this is the
      biggest naive phage display Nb library. Then Nbs against human procalcitonin
      (PCT) were isolated from this library. These Nbs showed comparable affinity and
      antigen-binding thermostability at 37 degrees C and 60 degrees C compared to the
      PCT Nbs from an immune phage-displayed library. Furthermore, two PCT Nbs that
      recognize unique epitopes on PCT have been successfully applied to develop a
      sandwich enzyme-linked immunosorbent assay (ELISA) to detect PCT, which showed a
      linear working range from 10-1000 ng/mL of PCT. CONCLUSION: We have constructed a
      large and diverse naive phage display Nb library, which potentially functioning
      as a good resource for selecting antigen-binders with high quality. Moreover,
      functional Nbs against PCT were successfully characterized and applied, providing
      great values on medical application.

PMID- 25944263
TI  - Optimization of Low Sodium Salts Mix for Shoestring Potatoes.
AB  - Several studies have shown the close relationship between the sodium consumption
      and health problems such as hypertension and cardiovascular disease. Thus, the
      demand for products with reduced sodium content, but with sensory quality, is
      increasing every day. In this context, this study aimed to optimize a low sodium
      salts mix using sodium chloride, potassium chloride, and monosodium glutamate to
      the development of shoestring potatoes with low sodium content and high sensory
      quality, through mixture design and response surface methodology. The salts mix
      that promotes the same salting power and similar sensory acceptability that the
      shoestring potatoes with 1.6% sodium chloride (ideal concentration) and at the
      same time promotes the greatest possible reduction of sodium, about 65%, should
      provide the composition as follows: 0.48% of sodium chloride, 0.92% of potassium
      chloride, and 0.43% of monosodium glutamate. 

PMID- 25944264
TI  - Cell population data in neonates: differences by age group and associations with
      perinatal factors.
AB  - INTRODUCTION: Cell population data (CPD) describe physical parameters of white
      blood cell subpopulations and are reported to be of some value in the diagnosis
      of sepsis in neonates. Before using the CPD for diagnosing sepsis, the baseline
      features of the CPD distribution in healthy neonates should be clarified. The aim
      of this study was to compare the CPD distributions of healthy neonates and other
      age groups and to identify perinatal factors that are associated with changes in
      the CPD distribution of healthy neonates. METHODS: The CPD distribution of 69
      samples from term neonates was compared with adolescents and adults. The CPD
      distribution of 163 samples from healthy neonates was analyzed in association
      with perinatal factors, including gestational age, chronologic age, birthweight,
      delivery mode, premature rupture of membranes, diabetes, and pregnancy-induced
      hypertension. RESULTS: The CPD distribution for term neonates was significantly
      different from those in adolescents and adults. The mean lymphocyte volume showed
      a negative correlation with gestational age at birth (r = -0.305; P < 0.01). The
      mean neutrophil volume was smaller in the cesarean section group than in the
      normal delivery group. The small for gestational age (SGA) group had smaller mean
      neutrophil volume and mean monocyte volume than the appropriate for gestational
      age group. CONCLUSION: The CPD distribution of healthy neonates differed from
      those of adolescents or adults, and the differences were associated with
      gestational age, delivery mode, and being SGA.

PMID- 25944266
TI  - Correlates of HPV vaccine uptake in school-based routine vaccination of
      preadolescent girls in Norway: A register-based study of 90,000 girls and their
      parents.
AB  - OBJECTIVE: To assess demographic, socioeconomic and behavioural correlates of HPV
      vaccination of preadolescent girls in a publicly funded, school-based vaccination
      programme. METHODS: Data for all Norwegian girls born 1997-1999, eligible for
      routine school-based HPV vaccination in 2009-2011 (n=90,842), and their
      registered mother and father, were merged from national registries. Correlates of
      girl vaccination status were analysed by unadjusted and multivariable logistic
      regression. RESULTS: In total, 78.2% of the girls received the first dose of the
      HPV vaccine, 74.6% received three doses, and 94.8% received the MMR vaccine.
      Correlates associated with initiation of HPV vaccination included parental age,
      income and education, maternal occupational status and cervical screening
      attendance, and girl receipt of the MMR vaccine. Rates of completion of HPV
      vaccination among initiators were high, and disparities in completion were
      negligible. Maternal and paternal correlates of daughter HPV vaccination status
      were similar. CONCLUSIONS: Routine school-based vaccination generally provides
      equitable delivery, yet some disparities exist. Information campaigns designed to
      reach the sub-groups with relatively low vaccine uptake could reduce disparities.
      In none of the sub-groups investigated did uptake of the HPV vaccine approach
      that of the MMR vaccine, further demonstrating a general potential for
      improvement in HPV vaccine uptake.

PMID- 25944267
TI  - Combining sigma-lognormal modeling and classical features for analyzing
      graphomotor performances in kindergarten children.
AB  - This paper investigates the advantage of using the kinematic theory of rapid
      human movements as a complementary approach to those based on classical dynamical
      features to characterize and analyze kindergarten children's ability to engage in
      graphomotor activities as a preparation for handwriting learning. This study
      analyzes nine different movements taken from 48 children evenly distributed among
      three different school grades corresponding to pupils aged 3, 4, and 5 years. On
      the one hand, our results show that the ability to perform graphomotor activities
      depends on kindergarten grades. More importantly, this study shows which
      performance criteria, from sophisticated neuromotor modeling as well as more
      classical kinematic parameters, can differentiate children of different school
      grades. These criteria provide a valuable tool for studying children's
      graphomotor control learning strategies. On the other hand, from a practical
      point of view, it is observed that school grades do not clearly reflect pupils'
      graphomotor performances. This calls for a large-scale investigation, using a
      more efficient experimental design based on the various observations made
      throughout this study regarding the choice of the graphic shapes, the number of
      repetitions and the features to analyze.

PMID- 25944265
TI  - Characterization of nerve and microvessel damage and recovery in type 1 diabetic
      mice after permanent femoral artery ligation.
AB  - Neuropathy is the most common complication of the peripheral nervous system
      during the progression of diabetes. The pathophysiology is unclear but may
      involve microangiopathy, reduced endoneurial blood flow, and tissue ischemia. We
      used a mouse model of type 1 diabetes to study parallel alterations of nerves and
      microvessels following tissue ischemia. We designed an easily reproducible model
      of ischemic neuropathy induced by irreversible ligation of the femoral artery. We
      studied the evolution of behavioral function, epineurial and endoneurial vessel
      impairment, and large nerve myelinated fiber as well as small cutaneous
      unmyelinated fiber impairment for 1 month following the onset of ischemia. We
      observed a more severe hindlimb dysfunction and delayed recovery in diabetic
      animals. This was associated with reduced density of large arteries in the
      hindlimb and reduced sciatic nerve epineurial blood flow. A reduction in sciatic
      nerve endoneurial capillary density was also observed, associated with a
      reduction in small unmyelinated epidermal fiber number and large myelinated
      sciatic nerve fiber dysfunction. Moreover, vascular recovery was delayed, and
      nerve dysfunction was still present in diabetic animals at day 28. This easily
      reproducible model provides clear insight into the evolution over time of the
      impact of ischemia on nerve and microvessel homeostasis in the setting of
      diabetes. (c) 2015 Wiley Periodicals, Inc. 

PMID- 25944269
TI  - A simple LC-MS/MS method for quantitative analysis of underivatized
      neurotransmitters in rats urine: assay development, validation and application in
      the CUMS rat model.
AB  - Many amino acid neurotransmitters in urine are associated with chronic stress as
      well as major depressive disorders. To better understand depression, an
      analytical LC-MS/MS method for the simultaneous determination of 11 underivatized
      neurotransmitters (4-aminohippurate, 5-HIAA, glutamate, glutamine, hippurate,
      pimelate, proline, tryptophan, tyramine, tyrosine and valine) in a single
      analytical run was developed. The advantage of this method is the simple
      preparation in that there is no need to deconjugate the urine samples. The
      quantification range was 25-12,800 ng mL(-1) with >85.8% recovery for all
      analytes. The nocturnal urine concentrations of the 11 neurotransmitters in
      chronic unpredictable mild stress (CUMS) model rats and control group (n = 12)
      were analyzed. A series of significant changes in urinary excretion of
      neurotransmitters could be detected: the urinary glutamate, glutamine, hippurate
      and tyramine concentrations were significantly lower in the CUMS group. In
      addition, the urinary concentrations of tryptophan as well as tyrosine were
      significantly higher in chronically stressed rats. This method allows the
      assessment of the neurotransmitters associated with CUMS in rat urine in a single
      analytical run, making it suitable for implementation as a routine technique in
      depression research.

PMID- 25944268
TI  - Repeated high-intensity exercise modulates Ca(2+) sensitivity of human skeletal
      muscle fibers.
AB  - The effects of short-term high-intensity exercise on single fiber contractile
      function in humans are unknown. Therefore, the purposes of this study were: (a)
      to access the acute effects of repeated high-intensity exercise on human single
      muscle fiber contractile function; and (b) to examine whether contractile
      function was affected by alterations in the redox balance. Eleven elite cross
      country skiers performed four maximal bouts of 1300 m treadmill skiing with 45
      min recovery. Contractile function of chemically skinned single fibers from
      triceps brachii was examined before the first and following the fourth sprint
      with respect to Ca(2+) sensitivity and maximal Ca(2+) -activated force. To
      investigate the oxidative effects of exercise on single fiber contractile
      function, a subset of fibers was incubated with dithiothreitol (DTT) before
      analysis. Ca(2+) sensitivity was enhanced by exercise in both MHC I (17%, P <
      0.05) and MHC II (15%, P < 0.05) fibers. This potentiation was not present after
      incubation of fibers with DTT. Specific force of both MHC I and MHC II fibers was
      unaffected by exercise. In conclusion, repeated high-intensity exercise increased
      Ca(2+) sensitivity in both MHC I and MHC II fibers. This effect was not observed
      in a reducing environment indicative of an exercise-induced oxidation of the
      human contractile apparatus. 

PMID- 25944270
TI  - Professor Herbert Lochs.

PMID- 25944271
TI  - Association between erythrocyte membrane fatty acids and biomarkers of
      dyslipidemia in the EPIC-Potsdam study.

PMID- 25944272
TI  - Pathways involved in the resolution of inflammatory joint disease.
AB  - A common feature of seasonal colds and other infections is painful joints. This
      is due to an acute reactive inflammatory arthritis which almost always resolves.
      Unfortunately, for some people the inflammation never completely resolves but
      rather precedes progression to chronic inflammatory arthritis. The existing dogma
      that accounts for why chronic inflammatory joint disease persists is that it is
      due to an excess of pro-inflammatory signals and that resolution occurs by pro
      inflammatory mediator catabolism. Recent discoveries have supported a new
      paradigm which proposes that the resolution of inflammation is an active process
      with genetic, molecular and cellular programs that promote catabasis. By seeking
      to understand the mechanisms behind the spontaneous resolution of inflammation,
      we can gain insight into why inflammation sometimes fails to resolve. This review
      seeks to highlight the mechanisms behind the resolution of joint inflammation and
      how endogenous pro-resolving mediators could be used to treat chronic persistent
      inflammatory joint disease. 

PMID- 25944273
TI  - Octreotide prevents liver failure through upregulating 5'-methylthioadenosine in
      extended hepatectomized rats.
AB  - BACKGROUND & AIMS: Insufficient liver regeneration and hepatocyte injury caused
      by excessive portal perfusion are considered to be responsible for post
      hepatectomy liver failure (PLF) or small-for-size syndrome in living-donor liver
      transplantation. Somatostatin can decrease portal vein pressure (PVP) but
      simultaneously inhibits liver regeneration. This interesting paradox motivated us
      to investigate the outcome of PLF in response to somatostatin treatment. METHODS:
      Rats receiving extended partial hepatectomy (90% PH) were treated with
      octreotide, a somatostatin analogue, or placebo. Animal survival, serum
      parameters and hepatic histology were evaluated. Metabolomic analysis was
      performed to investigate the effect of octreotide on hepatocyte metabolism.
      RESULTS: Despite significantly inhibiting early regeneration, octreotide
      application noticeably improved the hepatic histology, liver function and
      survival after PH but did not decrease the PVP level. Metabolomic analysis
      exhibited that octreotide profoundly and exclusively altered the levels of five
      metabolites that participate in or closely associate with the methionine cycle, a
      biochemical reaction that uniquely produces S-adenosylmethionine (SAMe), an
      active methyl residual donor for methyltransferase reactions. Among these
      metabolites, 5'-methylthioadenosine (MTA), a derivate of SAMe, increased three
      fold and was found independently improve the hepatic histology and reduce
      inflammatory cytokines in hepatectomized rats. CONCLUSIONS: Octreotide
      exclusively regulates the methionine cycle reaction and augments the MTA level in
      hepatocytes. MTA prominently protects hepatocytes against shear stress injury and
      reduces the secondary inflammation, thereby protecting rats from PLF.

PMID- 25944274
TI  - [MRI in dementia-type diseases].
AB  - Dementia-inducing conditions represent a leading cause of disability and are a
      major health concern in industrialized countries. The burden these conditions put
      on society is certain to rise in the context of an ever-increasing elderly
      population. As these conditions feature an insidious onset and overlapping
      clinical features, imaging is a powerful tool in refining the diagnosis and
      assessing the progression of dementing conditions. The radiologist needs to be
      aware of and be able to detect underlying pathologies which could be reversible.
      Furthermore, imaging is important not only in excluding other pathologies but
      also in improving diagnostic accuracy. This article presents the typical clinical
      presentations as well as magnetic resonance imaging (MRI) features of the
      degenerative and the non-degenerative causes of dementia. The focus is on the
      core knowledge for MRI diagnostics in dementing conditions and a brief
      presentation of the latest MRI techniques which may become a part of standard
      imaging protocols in the future. 

PMID- 25944275
TI  - [Differential diagnostics of dementia type diseases].
AB  - Dementia remains the most common neuropsychiatric disease in elderly people. This
      is not only a great burden for the affected person, but also for the entire
      society. Currently, it is estimated that more than one million people in Germany
      suffer from dementia. The incidence is about 244,000 people per year. There are
      different forms of dementia. Primary dementia is caused by neurodegenerative or
      vascular diseases. Approximately 90% of all dementia types in people over 65
      years of age are primary. Secondary dementia includes organic illness, which
      leads to dementing syndromes. Traumatic brain injury, tumor, medication and toxic
      substances, for instance, belong to these. Usually, if the underlying disease can
      be treated effectively, mental performance and cognition can be returned to
      normal.

PMID- 25944277
TI  - [To Prof. Dr. Gerhard van Kaick on his 80th birthday].

PMID- 25944276
TI  - [Teleradiological report turnaround times: An internal efficiency and quality
      control analysis].
AB  - AIMS: The teleradiological examinations performed at the Charite were analyzed
      for the purpose of internal quality and efficiency control. Data included the
      type and number of examinations performed, the time of day and week the
      examination was performed and the differences in teleradiologist report
      turnaround times. MATERIAL AND METHODS: A retrospective analysis of the radiology
      information system (RIS) database of all teleradiological computed tomography
      examinations performed at the Charite from 2011 through 2013 was carried out. The
      search retrieved 10,200 teleradiological examinations which were included in the
      analysis. The records were analyzed for the time of the day and week the
      examination was performed, the interval between examination and time of
      reporting, the type of teleradiological examination and the campus in which they
      were performed. RESULTS: The number of teleradiological examinations performed
      increased continuously during the observation period. Computed tomography of the
      head was the most frequently performed type of examination with 86%. Taking all
      forms of examination into consideration it took an average of 34 min until a
      report was written. Over the 3-year observation period the times remained
      virtually unaltered. CONCLUSION: During the 3-year observation period nearly
      constant report times could be observed in spite of the increased numbers of
      examinations. This indicates an efficiency enhancement and rational integration
      of teleradiology into the radiological workflow.

PMID- 25944278
TI  - Photoracemization of Blestriarene C and Its Analogs.
AB  - Two analogs of blestriarene C (4,4'-dimethoxy-1,1'-biphenanthrene-2,2',7,7'
      tetraol) bearing no 7,7'-dihydroxy (3) and 4,4'-dimethoxy groups were prepared.
      Unlike blestriarene C (1), compounds and , as well as 1,1'-biphenanthrene-2,2'
      diol (5), do not racemize under fluorescent lamp illumination. Cyclic voltammetry
      analysis reveals that compound has a lower half-wave potential (E(1/2)) than
      compounds , suggesting that a redox cycle is involved in the racemization.
      Compound racemizes by absorbing UV light corresponding to the (1) L(b) band.
      During the reaction, no side products are observed. The racemization is
      significantly inhibited under nitrogen. Based on these observations, we propose a
      feasible mechanism for the easy racemization of compound , which is mediated by a
      cation radical generated in situ by a reversible photo-induced oxygen oxidation.

PMID- 25944279
TI  - Male rats develop more severe experimental autoimmune encephalomyelitis than
      female rats: sexual dimorphism and diergism at the spinal cord level.
AB  - Compared with females, male Dark Agouti (DA) rats immunized for experimental
      autoimmune encephalomyelitis (EAE) with rat spinal cord homogenate in complete
      Freund's adjuvant (CFA) exhibited lower incidence of the disease, but the maximal
      neurological deficit was greater in the animals that developed the disease.
      Consistently, at the peak of the disease greater number of reactivated
      CD4+CD134+CD45RC- T lymphocytes was retrieved from male rat spinal cord. Their
      microglia/macrophages were more activated and produced greater amount of
      prototypic proinflammatory cytokines in vitro. Additionally, oppositely to the
      expression of mRNAs for IL-12/p35, IL-10 and IL-27/p28, the expression of mRNA
      for IL-23/p19 was upregulated in male rat spinal cord mononuclear cells.
      Consequently, the IL-17+:IFN-gamma+ cell ratio within T lymphocytes from their
      spinal cord was skewed towards IL-17+ cells. Within this subpopulation, the IL
      17+IFN-gamma+:IL-17+IL-10+ cell ratio was shifted towards IL-17+IFN-gamma+ cells,
      which have prominent tissue damaging capacity. This was associated with an
      upregulated expression of mRNAs for IL-1beta and IL-6, but downregulated TGF-beta
      mRNA expression in male rat spinal cord mononuclear cells. The enhanced GM-CSF
      mRNA expression in these cells supported the greater pathogenicity of IL-17+ T
      lymphocytes infiltrating male spinal cord. In the inductive phase of the disease,
      contrary to the draining lymph node, in the spinal cord the frequency of CD134+
      cells among CD4+ T lymphocytes and the frequency of IL-17+ cells among T
      lymphocytes were greater in male than in female rats. This most likely reflected
      an enhanced transmigration of mononuclear cells into the spinal cord (judging by
      the lesser spinal cord CXCL12 mRNA expression), the greater frequency of
      activated microglia/macrophages and the increased expression of mRNAs for Th17
      polarizing cytokines in male rat spinal cord mononuclear cells. Collectively, the
      results showed cellular and molecular mechanisms underlying the target organ
      specific sexual dimorphism in the T lymphocyte-dependent immune/inflammatory
      response, and suggested a substantial role for the target organ in shaping the
      sexually dimorphic clinical outcome of EAE. 

PMID- 25944280
TI  - Derivation of a bronchial genomic classifier for lung cancer in a prospective
      study of patients undergoing diagnostic bronchoscopy.
AB  - BACKGROUND: The gene expression profile of cytologically-normal bronchial airway
      epithelial cells has previously been shown to be altered in patients with lung
      cancer. Although bronchoscopy is often used for the diagnosis of lung cancer, its
      sensitivity is imperfect, especially for small and peripheral suspicious lesions.
      In this study, we derived a gene expression classifier from airway epithelial
      cells that detects the presence of cancer in current and former smokers
      undergoing bronchoscopy for suspect lung cancer and evaluated its sensitivity to
      detect lung cancer among patients from an independent cohort. METHODS: We
      collected bronchial epithelial cells (BECs) from the mainstem bronchus of 299
      current or former smokers (223 cancer-positive and 76 cancer-free subjects)
      undergoing bronchoscopy for suspected lung cancer in a prospective, multi-center
      study. RNA from these samples was run on gene expression microarrays for training
      a gene-expression classifier. A logistic regression model was built to predict
      cancer status, and the finalized classifier was validated in an independent
      cohort from a previous study. RESULTS: We found 232 genes whose expression levels
      in the bronchial airway are associated with lung cancer. We then built a
      classifier based on the combination of 17 cancer genes, gene expression
      predictors of smoking status, smoking history, and gender, plus patient age. This
      classifier had a ROC curve AUC of 0.78 (95% CI, 0.70-0.86) in patients whose
      bronchoscopy did not lead to a diagnosis of lung cancer (n = 134). In the
      validation cohort, the classifier had a similar AUC of 0.81 (95% CI, 0.73-0.88)
      in this same subgroup (n = 118). The classifier performed similarly across a
      range of mass sizes, cancer histologies and stages. The negative predictive value
      was 94% (95% CI, 83-99%) in subjects with a non-diagnostic bronchoscopy.
      CONCLUSION: We developed a gene expression classifier measured in bronchial
      airway epithelial cells that is able to detect lung cancer in current and former
      smokers who have undergone bronchoscopy for suspicion of lung cancer. Due to the
      high NPV of the classifier, it could potentially inform clinical decisions
      regarding the need for further invasive testing in patients whose bronchoscopy is
      non diagnostic.

PMID- 25944281
TI  - Measures of acute physiology, comorbidity and functional status to differentiate
      illness severity and length of stay among acute general medical admissions: a
      prospective cohort study.
AB  - BACKGROUND: Simple measures of acute physiologic compromise, functional status
      and comorbidity may help clinicians to make decisions relating to clinical care
      and resource utilisation. AIMS: To explore the usefulness of common assessment
      tools in predicting outcomes of (i) death or intensive care unit (ICU) admission
      and (ii) length of hospital stay at a busy tertiary hospital in Singapore.
      METHODS: Three hundred and ninety-eight consecutive admissions to two general
      medicine teams were prospectively assessed during 2 months in 2011. Patients were
      followed until discharge or transfer to ICU/high dependency unit (HDU). Data
      collected included routine demographic data, final diagnosis, comorbid conditions
      including a weighted prognostic comorbidity index (the updated Charlson index)
      and the modified Early Warning Score (MEWS) at presentation to the emergency
      department. The admission modified Barthel Index was recorded for patients aged
      65 and over. Death and total length of hospital stay were recorded in all cases.
      RESULTS: Of 398 patients, 16 (4 %) died or were transferred to ICU and 99 (25%)
      stayed for more than 7 days. Medical early warning (MEW) scores of >=5 were
      significantly associated with death or ICU admission (hazard ratio 5.50, 95%
      confidence interval 1.77-17.07, P = 0.003). There was no independent association
      between this outcome and the Charlson score or admission Barthel Index. Excess
      length of stay was associated with a modified Barthel Index <=17 and altered
      mental status at presentation. CONCLUSION: Among unselected general medical
      patients, MEW scores of >=5 were significantly associated with death or ICU
      admissions and only functional status and altered mental status were independent
      predictors of excess length of stay.

PMID- 25944282
TI  - Vasa expression in spermatogenic cells during the reproductive-cycle phases of
      Podarcis sicula (Reptilia, Lacertidae).
AB  - The vasa gene encodes a DEAD-box ATP-dependent RNA helicase that regulates the
      translation of multiple mRNAs involved in germ line differentiation. This protein
      has been deeply studied in many animals, but few data are available to date on
      reptiles. In this work, we sequenced a portion of Podarcis sicula vasa gene (Ps
      vasa), developed a specific antibody and verified its specificity. Using anti-Ps
      Vasa and confocal microscopy, we studied Vasa expression in male germ cells
      during the reproductive cycle of P. sicula: during full gonadal activity
      (spring), during regression of gonadal activity (summer) and during slow autumnal
      recrudescence. We also analyzed Vasa expression in young testes when the walls of
      the seminiferous tubules were forming. The aim was to verify if Vasa is involved
      in the process of male germ cell differentiation in all phases of the
      reproductive cycle. In adult testes, during full gonadal activity and during
      recrudescence, Vasa staining was detected from spermatogonia to spermatids. Vasa
      spots were also observed in the nucleus of germ cells supporting its function in
      different cellular compartments. No Vasa staining was observed in mature
      spermatozoa during the spring and mid-late November. The seminiferous epithelium
      analyzed in the summer appeared reduced with only spermatogonia, all Vasa
      immunostained, some in division to replace germ cells. In immature testes, the
      seminiferous epithelium contained only spermatogonia and spermatocytes. The clear
      immunostaining in their cytoplasm revealed that Vasa is already expressed in
      juvenile male gonads, suggesting a role in the differentiation process since P.
      sicula early developmental stages.

PMID- 25944283
TI  - Gut microbiome and innate immune response patterns in IgE-associated eczema.
AB  - BACKGROUND: Gut microbiome patterns have been associated with predisposition to
      eczema potentially through modulation of innate immune signalling. OBJECTIVE: We
      examined gut microbiome development in the first year of life in relation to
      innate immune responses and onset of IgE-associated eczema over the first 2.5
      years in predisposed children due to maternal atopy [www.anzctr.org.au, trial ID
      ACTRN12606000280505]. METHODS: Microbial composition and diversity were analysed
      with barcoded 16S rRNA 454 pyrosequencing in stool samples in pregnancy and at
      ages 1 week, 1 month and 12 months in infants (n = 10) who developed IgE
      associated eczema and infants who remained free of any allergic symptoms at 2.5
      years of age (n = 10). Microbiome data at 1 week and 1 month were analysed in
      relation to previously assessed immune responses to TLR 2 and 4 ligands at 6
      months of age. RESULTS: The relative abundance of Gram-positive Ruminococcaceae
      was lower at 1 week of age in infants developing IgE-associated eczema, compared
      with controls (P = 0.0047). At that age, the relative abundance of Ruminococcus
      was inversely associated with TLR2 induced IL-6 (-0.567, P = 0.042) and TNF-alpha
      (-0.597, P = 0.032); there was also an inverse association between the abundance
      of Proteobacteria (comprising Gram-negative taxa) and TLR4-induced TNF-alpha (rs
      = -0.629, P = 0.024). This relationship persisted at 1 month, with inverse
      associations between the relative abundance of Enterobacteriaceae (within the
      Proteobacteria phylum) and TLR4-induced TNF-alpha (rs = -0.697, P = 0.038) and
      Enterobacteriaceae and IL-6 (rs = -0.709, P = 0.035). Mothers whose infants
      developed IgE-associated eczema had lower alpha-diversity of Bacteroidetes (P =
      0.04) although this was not seen later in their infants. At 1 year, alpha
      diversity of Actinobacteria was lower in infants with IgE-associated eczema
      compared with controls (P = 0.002). CONCLUSION AND CLINICAL RELEVANCE: Our
      findings suggest that reduced relative abundance of potentially immunomodulatory
      gut bacteria is associated with exaggerated inflammatory cytokine responses to
      TLR-ligands and subsequent development of IgE-associated eczema.

PMID- 25944284
TI  - Tissue Doppler-Derived Myocardial Acceleration during Isovolumetric Contraction
      Predicts Pulmonary Capillary Wedge Pressure in Patients with Significant Mitral
      Regurgitation.
AB  - The aim of this study was to determine whether isovolumic contraction velocity
      (IVV) and acceleration (IVA) predict pulmonary capillary wedge pressure (PCWP) in
      mitral regurgitation. Forty-four patients with mitral regurgitation were studied.
      PCWP was invasively measured. IVV, IVA and the ratio IVRT/Te'-E (where IVRT =
      isovolumic relaxation time, and Te'-E = time difference between the onset of
      mitral annular e' and mitral flow E waves) were measured. Mean age was 59.2 +/-
      13.3 y. Twenty-six patients had an ejection fraction >=55%, and 18 patients had
      an ejection fraction <55%. IVRT/Te'-E was impossible in 11 patients because Te'-E
      = zero. PCWP correlated with IVV, IVA and IVRT/Te'-E; overall (r = -0.714, -0.892
      and, -0.752, all p < 0.001), ejection fraction >=55 (r = -0.467, -0.749, -0.639,
      p = 0.016, <0.001, 0.003) and ejection fraction <55% (r = -0.761, -0.911 and 
      0.833, all p < 0.001). Similar correlations were found for sinus and atrial
      fibrillation. Our study suggests that IVV and IVA correlate with PCWP in patients
      with mitral regurgitation irrespective of systolic function or rhythms and, thus,
      can be alternatives to the tedious IVRT/Te'-E, especially when impossible because
      Te'-E = 0. 

PMID- 25944285
TI  - Comparison Between Neck and Shoulder Stiffness Determined by Shear Wave
      Ultrasound Elastography and a Muscle Hardness Meter.
AB  - The goals of this study were to compare neck and shoulder stiffness values
      determined by shear wave ultrasound elastography with those obtained with a
      muscle hardness meter and to verify the correspondence between objective and
      subjective stiffness in the neck and shoulder. Twenty-four young men and women
      participated in the study. Their neck and shoulder stiffness was determined at
      six sites. Before the start of the measurements, patients rated their present
      subjective symptoms of neck and shoulder stiffness on a 6-point verbal scale. At
      all measurement sites, the correlation coefficients between the values of muscle
      hardness indices determined by the muscle hardness meter and shear wave
      ultrasound elastography were not significant. Furthermore, individuals'
      subjective neck and shoulder stiffness did not correspond to their objective
      symptoms. These results suggest that the use of shear wave ultrasound
      elastography is essential to more precisely assess neck and shoulder stiffness. 

PMID- 25944286
TI  - Experimental and Numerical Determination of the Local Temperature Distribution
      during Phacoemulsification and Comparison of Different Surgery Situations within
      Enucleated Porcine Eyes.
AB  - Phacoemulsification, a common treatment for cataract, is accompanied by cell
      damage at the corneal endothelium. Thermal exposure during treatment has been
      considered a reason for this damage, but a thorough experimental and theoretical
      assessment of the local temperature distribution inside the eye had not yet been
      conducted. Measurements in porcine eyes and a finite-element simulation enabled
      such an assessment and localized the highest temperature rise very close to the
      probe. The results described in this study indicate that a distance of 1 mm
      between the probe and the endothelium should be maintained during treatment as a
      safety margin, especially when fluid flow is blocked. The highest measured
      temperature rise with surgically reasonable system settings and unblocked fluid
      flow was 1.11 degrees C. The finite-element simulation described here is able to
      calculate the temperature rise at the endothelium and could serve as a tool for
      comparing arbitrary surgical situations with respect to thermal exposure of the
      endothelium. 

PMID- 25944287
TI  - Prussian Blue Derived Nanoporous Iron Oxides as Anticancer Drug Carriers for
      Magnetic-Guided Chemotherapy.
AB  - New nanoporous iron oxide nanoparticles with superparamagnetic behavior were
      successfully synthesized from Prussian blue (PB) nanocubes through a thermal
      conversion method and applied to the intracellular drug-delivery systems (DDS) of
      bladder cancer cells (i.e., T24) with controlled release and magnetic guiding
      properties. The results of the MTT assay and confocal laser scanning microscopy
      indicate that the synthesized iron oxide nanoparticles were successfully uptaken
      by T24 cells with excellent biocompatibility. An anticancer drug, that is,
      cisplatin, was used as a model drug, and its loading/release behavior was
      investigated. The intracellular drug delivery efficiency was greatly enhanced for
      the cisplatin-loaded, PB-derived, magnetic-guided drug-delivery system compared
      with the non-drug case. The synthesized nanomaterials show great potential as
      drug vehicles with high biocompatibility, controlled release, and magnetic
      targeting features for future intracellular DDS. 

PMID- 25944288
TI  - Cepstral Peak Sensitivity: A Theoretic Analysis and Comparison of Several
      Implementations.
AB  - OBJECTIVE: The aim of this study was to develop a theoretic analysis of the
      cepstral peak (CP), to compare several CP software programs, and to propose
      methods for reducing variability in CP estimation. STUDY DESIGN: Descriptive,
      experimental study. METHODS: The theoretic CP value of a pulse train was derived
      and compared with estimates computed for pulse train WAV files using available CP
      software programs: (1) Hillenbrand's CP prominence (CPP) software (Western
      Michigan University, Kalamazoo, MI), (2) KayPENTAX (Montvale, NJ) Multi-Speech
      implementation of CPP, and (3) a MATLAB (The Mathworks, Natick, MA, version
      R2014a) implementation using cepstral interpolation. The CP variation was also
      investigated for synthetic breathy vowels. RESULTS: For pulse trains with period
      T samples, the theoretic CP is 1/2+epsilon/T, |epsilon|<0.1 for all pulse trains
      (epsilon=0 for integer T). For fundamental frequencies between 70 and 230Hz, the
      CP mean+/-standard deviation was 0.496+/-0.002 using cepstral interpolation and
      0.29+/-0.03 using Hillenbrand's software, whereas CPP was 35.0+/-3.8dB using
      Hillenbrand's software and 20.5+/-2.7dB using KayPENTAX's software. The CP and
      CPP versus signal-to-noise ratio for synthetic breathy vowels were fit to a
      logistic model for the Hillenbrand (R(2)=0.92) and KayPENTAX (R(2)=0.82)
      estimators as well as an ideal estimator (R(2)=0.98), which used a period
      synchronous analysis. CONCLUSIONS: The findings indicate that several variables
      unrelated to the signal itself impact CP values, with some factors introducing
      large variability in CP values that would otherwise be attributed to the signal
      (eg, voice quality). Variability may be reduced by using a period-synchronous
      analysis with Hann windows.

PMID- 25944289
TI  - State-Space Approach to Structural Representation of Perturbed Pitch Period
      Sequences in Voice Signals.
AB  - OBJECTIVES: The aim of this study was to propose a state space-based approach to
      model perturbed pitch period sequences (PPSs), extracted from real sustained
      vowels, combining the principal features of disturbed real PPSs with structural
      analysis of stochastic time series and state space methods. METHODS: The PPSs
      were obtained from a database composed of 53 healthy subjects. State space models
      were developed taking into account different structures and complexity levels.
      PPS features such as trend, cycle, and irregular structures were considered.
      Model parameters were calculated using optimization procedures. For each PPS,
      state estimates were obtained combining the developed models and diffuse
      initialization with filtering and smoothing methods. Statistical tests were
      applied to objectively evaluate the performance of this method. RESULTS:
      Statistical tests demonstrated that the proposed approach correctly represented
      more than the 75% of the database with a significance value of 0.05. In the
      analysis, structural estimates suitably characterized the dynamics of the PPSs.
      Trend estimates proved to properly represent slow long-term dynamics, whereas
      cycle estimates captured short-term autoregressive dependencies. CONCLUSIONS: The
      present study demonstrated that the proposed approach is suitable for
      representing and analyzing real perturbed PPSs, also allowing to extract further
      information related to the phonation process.

PMID- 25944290
TI  - Influence of F0 and Sequence Length of Audio and Electroglottographic Signals on
      Perturbation Measures for Voice Assessment.
AB  - OBJECTIVE: Within the functional assessment of voice disorders, an objective
      analysis of measured parameters from audio, electroglottographic (EGG), or visual
      signals is desired. In a typical clinical situation, reliable objective analysis
      is not always possible due to missing standardization and unknown stability of
      the clinical parameters. The aim of this study was to investigate the
      robustness/stability of measured clinical parameters of the audio and EGG signals
      in a typical clinical setting to ensure a reliable objective analysis. In
      particular, the influence of F0 and of the sequence length on several definitions
      of jitter and shimmer will be analyzed. PATIENTS AND METHODS: Seventy-four young
      healthy women produced a sustained vowel /a/ and an upward triad with abrupt
      changeovers. Different sequence lengths (100, 150, 500, and 1000 ms) of sustained
      phonation and triads (100 and 150 ms) were extracted from the audio and EGG
      signals. In total, six variations of jitter and four variations of shimmer
      parameters were analyzed. RESULTS: Jitter%, Jitter11p, and JitterPPQ of the audio
      signal as well as Jittermean, Shimmer, and Shimmer11p of the EGG signal are
      unaffected by both sequence length and F0. CONCLUSIONS: Influence of F0 and
      sequence length on several perturbation measures of the audio and EGG signals was
      identified. For an objective clinical voice assessment, unaffected definitions of
      jitter and shimmer should be preferred and applied to enable comparability
      between different recordings, examinations, and studies.

PMID- 25944291
TI  - Quantitative Study for the Surface Dehydration of Vocal Folds Based on High-Speed
      Imaging.
AB  - OBJECTIVES: From the perspective of the glottal area and mucosal wave,
      quantitatively estimate the differences of vocal fold on laryngeal activity
      during phonation at three different dehydration levels. STUDY DESIGN: Controlled
      three sets of tests. METHODS: A dehydration experiment for 10 excised canine
      larynges was conducted at 16 cm H2O. According to the dehydration cycle time (H),
      dehydration levels were divided into three degrees (0% H, 50% H, 75% H). The
      glottal area and mucosal wave under three dehydration levels were extracted from
      high-speed images and digital videokymography (DKG) image sequences. Direct and
      non-direct amplitude components were derived from glottal areas. The amplitude
      and frequency of mucosal wave were calculated from DKG image sequences. These
      parameters in condition of three dehydration levels were compared for statistical
      analysis. RESULTS AND DISCUSSIONS: The results showed a significant difference in
      direct (P = 0.001; P = 0.005) and non-direct (P = 0.005; P = 0.016) components of
      glottal areas between every two different dehydration levels. Considering the
      right-upper, right-lower, left-upper, and left-lower of vocal fold, the
      amplitudes of mucosal waves consistently decreased with increasing of dehydration
      levels. But, there was no significant difference in frequency. CONCLUSIONS:
      Surface dehydration could give rise to complex variation of vocal fold on tissues
      and vibratory mechanism, which should need analyzing from multiple perspectives.
      The results suggested that the combination of glottal area and mucosal wave could
      be better to research the change of vocal fold at different dehydrations. It
      would become a better crucial research tool for the clinical treatment of
      dehydration-induced laryngeal pathologies.

PMID- 25944292
TI  - Voice Onset Time for the Word-Initial Voiceless Consonant /t/ in Japanese
      Spasmodic Dysphonia-A Comparison With Normal Controls.
AB  - OBJECTIVES: Voice onset time (VOT) for word-initial voiceless consonants in
      adductor spasmodic dysphonia (ADSD) and abductor spasmodic dysphonia (ABSD)
      patients were measured to determine (1) which acoustic measures differed from the
      controls and (2) whether acoustic measures were related to the pause or silence
      between the test word and the preceding word. METHODS: Forty-eight patients with
      ADSD and nine patients with ABSD, as well as 20 matched normal controls read a
      story in which the word "taiyo" (the sun) was repeated three times, each
      differentiated by the position of the word in the sentence. The target of
      measurement was the VOT for the word-initial voiceless consonant /t/. RESULTS:
      When the target syllable appeared in a sentence following a comma, or at the
      beginning of a sentence following a period, the ABSD patients' VOTs were
      significantly longer than those of the ADSD patients and controls. Abnormal
      prolongation of the VOTs was related to the pause or silence between the test
      word and the preceding word. CONCLUSIONS: VOTs in spasmodic dysphonia (SD) may
      vary according to the SD subtype or speaking conditions. VOT measurement was
      suggested to be a useful method for quantifying voice symptoms in SD.

PMID- 25944293
TI  - Multidimensional Analysis on the Effect of Vocal Function Exercises on Aged Vocal
      Fold Atrophy.
AB  - OBJECTIVES: Age-related voice change is characterized as weak, harsh, and
      breathy. These changes are caused by histologic alteration of the lamina propria
      of the vocal fold mucosa as well as atrophy of the thyroarytenoid muscle. Several
      therapeutic strategies involving laryngeal framework surgery and injection
      laryngoplasty have been tried, but effects have been limited. Vocal function
      exercises (VFE) have been used to treat age-related vocal fold atrophy although
      the effectiveness has been shown with limited analysis. The present study aims to
      determine the effectiveness of VFE for the treatment of aged atrophy using
      multidimensional analysis. STUDY DESIGN: This is a retrospective study. METHODS:
      Sixteen patients with vocal fold atrophy aged 65-81 years underwent voice therapy
      using VFE. Six patients with vocal fold atrophy aged 65-85 years were involved as
      a historical control group. The grade, roughness, breathiness, asthenia, strain
      (GRBAS) scale, stroboscopic examinations, aerodynamic assessment, acoustic
      analysis, and Voice Handicap Index-10 (VHI-10) were performed before and after
      VFE. Normalized mucosal wave amplitude (NMWA), normalized glottal gap (NGG), and
      bowing index (BI) were measured by image analysis during stroboscopic
      examinations. RESULTS: After VFE, significant improvements were shown in GRBAS,
      maximum phonation time, jitter, NMWA, NGG, and VHI-10 although BI has not changed
      significantly. There were no significant improvements in the historical control.
      CONCLUSIONS: The data suggest that VFE produces significant improvement in
      subjective, objective, and patient self-evaluation and deserves further attention
      as a treatment for aged atrophy of the vocal fold. It was also suggested that VFE
      does not improve the vocal fold bowing but may improve muscular function during
      voicing.

PMID- 25944294
TI  - Comprehensive Outcome Researches of Intralesional Steroid Injection on Benign
      Vocal Fold Lesions.
AB  - OBJECTIVE: This study investigated multidimensional treatment outcomes, including
      prognostic factors and side effects of vocal fold steroid injection (VFSI).
      METHODS: We recruited 126 consecutive patients, including patients with 49
      nodules, 47 polyps, and 30 mucus retention cysts. All the patients received VFSI
      under local anesthesia in the office settings. Treatment outcomes were evaluated
      1 and 2 months after the procedure, including endoscopic evaluation, perceptual
      voice quality (GRB scores), acoustic analysis, and 10-item Voice Handicap Index
      (VHI-10). RESULTS: More than 80% of the patients reported subjective improvements
      after VFSI. Objective measurements revealed significant improvements from
      baseline in most of the outcome parameters (P<0.05). Higher occupational vocal
      demands and fibrotic vocal nodules were significantly associated with poorer
      clinical responses as measured by the VHI-10 and GRB scores, respectively. For
      vocal polyps, dysphonia for more than 12 months were significantly associated
      with higher postoperative VHI-10 scores, whereas patients with laryngopharyngeal
      reflux (LPR) showed significantly poor postoperative voice quality as measured by
      GRB scores. Side effects after VFSI included hematoma (27%), triamcinolone
      deposits (4%), and vocal atrophy (1%), which resolved spontaneously within 1-2
      months. Presentation with vocal fold ectasias/varicosities and higher vocal
      demands were significantly correlated with postoperative vocal hematoma.
      CONCLUSIONS: This study demonstrated significant improvements after VFSI in vocal
      nodules, polyps, and cysts. Occupational vocal demand and subtypes of vocal
      nodules are closely related to the treatment outcomes after VFSI, whereas symptom
      duration and LPR were significant prognostic factors for VFSI treatment outcomes
      in vocal polyps. Side effects after receiving VFSI were mostly self-limited
      without sequel, whereas the incidence rates might be varied by the injection
      approach and the timing for postoperative follow-up.

PMID- 25944295
TI  - Glottal Adduction and Subglottal Pressure in Singing.
AB  - Previous research suggests that independent variation of vocal loudness and
      glottal configuration (type and degree of vocal fold adduction) does not occur in
      untrained speech production. This study investigated whether these factors can be
      varied independently in trained singing and how subglottal pressure is related to
      average glottal airflow, voice source properties, and sound level under these
      conditions. A classically trained baritone produced sustained phonations on the
      endoscopic vowel [i:] at pitch D4 (approximately 294 Hz), exclusively varying
      either (a) vocal register; (b) phonation type (from "breathy" to "pressed" via
      cartilaginous adduction); or (c) vocal loudness, while keeping the others
      constant. Phonation was documented by simultaneous recording of videokymographic,
      electroglottographic, airflow and voice source data, and by percutaneous
      measurement of relative subglottal pressure. Register shifts were clearly marked
      in the electroglottographic wavegram display. Compared with chest register,
      falsetto was produced with greater pulse amplitude of the glottal flow, H1-H2,
      mean airflow, and with lower maximum flow declination rate (MFDR), subglottal
      pressure, and sound pressure. Shifts of phonation type
      (breathy/flow/neutral/pressed) induced comparable systematic changes. Increase of
      vocal loudness resulted in increased subglottal pressure, average flow, sound
      pressure, MFDR, glottal flow pulse amplitude, and H1-H2. When changing either
      vocal register or phonation type, subglottal pressure and mean airflow showed an
      inverse relationship, that is, variation of glottal flow resistance. The direct
      relation between subglottal pressure and airflow when varying only vocal loudness
      demonstrated independent control of vocal loudness and glottal configuration.
      Achieving such independent control of phonatory control parameters would be an
      important target in vocal pedagogy and in voice therapy. 

PMID- 25944296
TI  - The Effect of Growing Rod Treatment on Hemoglobin and Hematocrit Levels in Early
      onset Scoliosis.
AB  - BACKGROUND: This study examines preoperative hemoglobin (Hgb) and hematocrit
      (Hct) levels in a group of early-onset scoliosis (EOS) patients and the effect of
      distraction-based growing rods (GRs) on these levels. Children with EOS are at
      risk for respiratory insufficiency and chronic hypoxemia. Increased Hgb and Hct
      levels have been identified as surrogate markers for chronic hypoxemia. A study
      of patients who underwent VEPTR surgery showed a significant decrease in Hgb
      levels following surgery. METHODS: Data were retrospectively collected on 66 EOS
      patients without confounding respiratory issues or oxygen dependence who were
      treated with GRs at 5 institutions. Average age at initial surgery was 5.5 years.
      Patients were followed for a minimum of 2 years (average 3.7 y). Preoperative and
      postoperative Hgb and Hct levels were converted to Z-scores based on age-adjusted
      mean blood indices and were compared using a paired t test. RESULTS: The
      prevalence of elevated Hgb and Hct levels (Z-score >2) preoperatively was 15%
      (10/66) and 19% (12/64), respectively. The average Hgb Z-score decreased from
      0.20 to -0.31 (P=0.005) 6 to 24 months following surgery and the Hct Z-score
      decreased from 0.31 to -0.28 (P=0.002) 6 to 24 months following surgery.
      CONCLUSIONS: Following distraction-based GR treatment of children with EOS there
      was a significant decrease in both their Hgb and Hct. This is a physiological
      marker of decreased hypoxemia and improved pulmonary function. LEVEL OF EVIDENCE:
      Level III-therapeutic study.

PMID- 25944297
TI  - Skin thickness in young infants and adolescents: Applications for intradermal
      vaccination.
AB  - As compared with standard intramuscular and subcutaneous vaccines, intradermal
      (ID) vaccines elicit a more potent immune response in both adults and children,
      with equivalent dosage or antigen dose sparing. Recently, various devices for ID
      injection have been developed; the length of needles ranges in 0.6-1.5 mm.
      However, skin thickness must be measured to determine optimal needle length for
      ID vaccines. Use of ID vaccines in infants and children is appealing because
      children require more vaccines than do adults; however, information on skin
      thickness in infants and children is limited. We used ultrasound echography to
      measure skin thickness in Japanese infants aged 2 months (n=78) and adolescents
      aged 13-15 years (n=82). Mean (range) deltoid and suprascapular skin thickness
      was 1.67 mm (1.16-2.39 mm) and 1.83 mm (1.24-2.60 mm), respectively, in infants
      and 1.81 mm (1.25-3.00 mm) and 2.43 mm (1.51-3.95 mm), respectively, in
      adolescents. Among infants who underwent re-measurement of skin thickness at age
      6 months (n=11), mean deltoid skin thickness (1.84 mm) was significantly greater
      than at age 2 months (1.60 mm) (P<0.001). In contrast, no significant difference
      was observed in suprascapular skin thickness (1.79 mm vs. 1.67 mm, respectively;
      P=0.17). Gender was not associated with skin thickness in either age group. Skin
      thickness was positively correlated with body weight in adolescents (r=0.43,
      P<0.001 in deltoid region; r=0.30, P=0.01 in suprascapular region). In
      conclusion, this is the first study to evaluate skin thickness in different age
      groups of children, including at age 2 months. Skin thickness gradually increased
      from age 2 months to age 13-15 years, but no consistent trend was noted in
      analysis stratified by measurement site, gender, or age. These findings suggest
      that an appropriate length of ID device needle for infants and children is likely
      to be less than 1.2mm and a special device with shorter length of needle is
      warranted for infants and children.

PMID- 25944298
TI  - Conformational instability governed by disulfide bonds partitions the dominant
      from subdominant helper T-cell responses specific for HIV-1 envelope glycoprotein
      gp120.
AB  - Most individuals infected with human immunodeficiency virus type 1 (HIV-1)
      generate a CD4(+) T-cell response that is dominated by a few epitopes.
      Immunodominance may be counterproductive because a broad CD4(+) T-cell response
      is associated with reduced viral load. Previous studies indicated that antigen
      three-dimensional structure controls antigen processing and presentation and
      therefore CD4(+) T-cell epitope dominance. Dominant epitopes occur adjacent to
      the V1-V2, V3, and V4 loops because proteolytic antigen processing in the loops
      promotes presentation of adjacent sequences. In this study, three gp120 (strain
      JR-FL) variants were constructed, in which deletions of single outer-domain
      disulfide bonds were expected to introduce local conformational flexibility and
      promote presentation of additional CD4(+) T-cell epitopes. Following mucosal
      immunization of C57BL/6 mice with wild-type or variant gp120 lacking the V3
      flanking disulfide bond, the typical pattern of dominant epitopes was observed,
      suggesting that the disulfide bond posed no barrier to antigen presentation. In
      mice that lacked gamma interferon-inducible lysosomal thioreductase (GILT),
      proliferative responses to the typically dominant epitopes of gp120 were
      selectively depressed, and the dominance pattern was rearranged. Deletion of the
      V3-flanking disulfide bond or one of the V4-flanking disulfide bonds partially
      restored highly proliferative responses to the typically dominant epitopes. These
      results reveal an acute dependence of dominant CD4(+) T-cell responses on the
      native gp120 conformation. 

PMID- 25944299
TI  - Parental reminder, recall and educational interventions to improve early
      childhood immunisation uptake: A systematic review and meta-analysis.
AB  - Vaccination is one of the most effective ways of reducing childhood mortality.
      Despite global uptake of childhood vaccinations increasing, rates remain sub
      optimal, meaning that vaccine-preventable diseases still pose a public health
      risk. A range of interventions to promote vaccine uptake have been developed,
      although this range has not specifically been reviewed in early childhood. We
      conducted a systematic review and meta-analysis of parental interventions to
      improve early childhood (0-5 years) vaccine uptake. Twenty-eight controlled
      studies contributed to six separate meta-analyses evaluating aspects of parental
      reminders and education. All interventions were to some extent effective,
      although findings were generally heterogeneous and random effects models were
      estimated. Receiving both postal and telephone reminders was the most effective
      reminder-based intervention (RD=0.1132; 95% CI=0.033-0.193). Sub-group analyses
      suggested that educational interventions were more effective in low- and middle
      income countries (RD=0.13; 95% CI=0.05-0.22) and when conducted through
      discussion (RD=0.12; 95% CI=0.02-0.21). Current evidence most supports the use of
      postal reminders as part of the standard management of childhood immunisations.
      Parents at high risk of non-compliance may benefit from recall strategies and/or
      discussion-based forums, however further research is needed to assess the
      appropriateness of these strategies. 

PMID- 25944300
TI  - Oral delivery of wafers made from HBsAg-expressing maize germ induces long-term
      immunological systemic and mucosal responses.
AB  - BACKGROUND: The hepatitis B surface antigen (HBsAg) has been administered over
      the last 20 years as a parenteral vaccine against the hepatitis B virus (HBV).
      Despite high seroconversion rates, chronic infection rates are still high
      worldwide. Orally delivered vaccines provide a practical alternative to injected
      vaccines, potentially helping poorly responding populations and providing a
      viable alternative for populations in remote locations. Anamnestic responses are
      vital to establishing the efficacy of a given vaccine and have been assessed in
      this study using a plant-based oral delivery platform expressing HBsAg. METHODS:
      Long-term immunological memory was assessed in mice injected with a primary dose
      of Recombivax and boosted with orally-delivered HBsAg wafers, control wafers, or
      parenterally-delivered commercial vaccine (Recombivax). RESULTS: Mice boosted
      with HBsAg orally-administered wafers displayed sharp increases in mucosal IgA
      titers in fecal material and steep increases in serum IgA, whereas mice boosted
      with Recombivax showed no detectable levels of IgA in either fecal or serum
      samples following four boosting treatments. Long-term memory in the orally
      treated mice was evidenced by sustained fecal IgA, and serum IgA, IgG, and mIU/mL
      over one year, while Recombivax-treated mice displayed sustained serum IgG and
      mIU/mL. Furthermore, sharp increases in these same antibodies were induced after
      re-boosting at 47 and 50 weeks post-primary injection. CONCLUSIONS: Orally
      delivered vaccines can provide long-term immune responses mucosally and
      systemically. For sexually-transmitted diseases that can be acquired at mucosal
      surfaces, such as HBV, an oral delivery platform may provide added protection
      over a conventional parenterally administered vaccine.

PMID- 25944301
TI  - The Rebirth of Waste Cooking Oil to Novel Bio-based Surfactants.
AB  - Waste cooking oil (WCO) is a kind of non-edible oil with enormous quantities and
      its unreasonable dispose may generate negative impact on human life and
      environment. However, WCO is certainly a renewable feedstock of bio-based
      materials. To get the rebirth of WCO, we have established a facile and high-yield
      method to convert WCO to bio-based zwitterionic surfactants with excellent
      surface and interfacial properties. The interfacial tension between crude oil and
      water could reach ultra-low value as 0.0016 mN m(-1) at a low dosage as 0.100 g
      L(-1) of this bio-based surfactant without the aid of extra alkali, which shows a
      strong interfacial activity and the great potential application in many
      industrial fields, in particular, the application in enhanced oil recovery in
      oilfields in place of petroleum-based surfactants.

PMID- 25944302
TI  - Natural carbon-based dots from humic substances.
AB  - For the first time, abundant natural carbon-based dots were found and studied in
      humic substances (HS). Four soluble HS including three humic acids (HA) from
      different sources and one fulvic acids (FA) were synthetically studied.
      Investigation results indicate that all the four HS contain large quantities of
      Carbon-based dots. Carbon-based dots are mainly small-sized graphene oxide nano
      sheets or oxygen-containing functional group-modified graphene nano-sheets with
      heights less than 1 nm and lateral sizes less than 100 nm. Carbon-based
      nanomaterials not only contain abundant sp2-clusters but also a large quantity of
      surface states, exhibiting unique optical and electric properties, such as
      excitation-dependent fluorescence, surface states-originated
      electrochemiluminescence, and strong electron paramagnetic resonance. Optical and
      electric properties of these natural carbon-based dots have no obvious
      relationship to their morphologies, but affected greatly by their surface states.
      Carbon-based dots in the three HS have relative high densities of surface states
      whereas the FA has the lowest density of surface states, resulting in their
      different fluorescence properties. The finding of carbon-based dots in HS
      provides us new insight into HS, and the unique optical properties of these
      natural carbon-based dots may give HS potential applications in areas such as bio
      imaging, bio-medicine, sensing and optoelectronics.

PMID- 25944303
TI  - Reduced doses of cladribine and cytarabine regimen was effective and well
      tolerated in patients with refractory-risk multisystem Langerhans cell
      histiocytosis.

PMID- 25944305
TI  - The origins of reproductive isolation in plants.
AB  - Reproductive isolation in plants occurs through multiple barriers that restrict
      gene flow between populations, but their origins remain uncertain. Work in the
      past decade has shown that postpollination barriers, such as the failure to form
      hybrid seeds or sterility of hybrid offspring, are often less strong than
      prepollination barriers. Evidence implicates multiple evolutionary forces in the
      origins of reproductive barriers, including mutation, stochastic processes and
      natural selection. Although adaptation to different environments is a common
      element of reproductive isolation, genomic conflicts also play a role, including
      female meiotic drive. The genetic basis of some reproductive barriers,
      particularly flower colour influencing pollinator behaviour, is well understood
      in some species, but the genetic changes underlying many other barriers,
      especially pollen-stylar interactions, are largely unknown. Postpollination
      barriers appear to accumulate at a faster rate in annuals compared with
      perennials, due in part to chromosomal rearrangements. Chromosomal changes can be
      important isolating barriers in themselves but may also reduce the recombination
      of genes contributing to isolation. Important questions for the next decade
      include identifying the evolutionary forces responsible for chromosomal
      rearrangements, determining how often prezygotic barriers arise due to selection
      against hybrids, and establishing the relative importance of genomic conflicts in
      speciation.

PMID- 25944304
TI  - beta cell dysfunction versus insulin resistance in the pathogenesis of type 2
      diabetes in East Asians.
AB  - Type 2 diabetes (T2DM) is one of the most serious global health problems and is
      mainly a result of the drastic increase in East Asia, which includes over a
      fourth of the global diabetes population. Lifestyle factors and ethnicity are two
      determinants in the etiology of T2DM, and lifestyle changes such as higher fat
      intake and less physical activity link readily to T2DM in East Asians. It is
      widely recognized that T2DM in East Asians is characterized primarily by beta
      cell dysfunction, which is evident immediately after ingestion of glucose or
      meal, and less adiposity compared to the disease in Caucasians. These
      pathophysiological differences have an important impact on therapeutic
      approaches. Here, we revisit the pathogenesis of T2DM in light of beta cell
      dysfunction versus insulin resistance in East Asians and discuss ethnic
      differences in the contributions of insulin secretion and insulin resistance,
      together with incretin secretin and action, to glucose intolerance.

PMID- 25944306
TI  - Quality improvement in pediatric sepsis.
AB  - PURPOSE OF REVIEW: Although there is abundant literature detailing the impact of
      quality improvement in adult sepsis, the pediatric literature is lacking. Despite
      consensus definitions for sepsis, which patients along the sepsis spectrum should
      receive aggressive management and the exact onset of sepsis ('time zero') are not
      clearly established. In the adult emergency department (ED), sepsis onset is
      defined as the time of entry into the ED; however, this definition cannot be
      applied to hospitalized patients or patients who evolve during their ED course.
      Since the time of sepsis onset will dictate the timeliness of subsequent process
      measures, the variable definitions in the literature make it difficult to
      generalize findings among prior studies. RECENT FINDINGS: Despite the variation
      in defining time zero, aggressive fluid administration, timely antibiotics, and
      compliance with sepsis bundles have been shown to improve mortality and to reduce
      hospital and intensive care length of stay. In addition, early identification
      tools show promise in beginning to define sepsis onset and retrospective search
      tools may allow improved case finding of those children of concern for sepsis.
      SUMMARY: Quality improvement in pediatric sepsis is evolving. As we continue to
      define quality measures, we must standardize the definition of sepsis onset. This
      definition should be applicable to any treatment venue to ensure measures can be
      evaluated across all settings. In addition, we must delineate which patients
      along the sepsis spectrum should be candidates for timely interventions and
      standardize other outcome measures beyond mortality.

PMID- 25944307
TI  - Hirschsprung's associated enterocolitis.
AB  - PURPOSE OF REVIEW: Hirschsprung's disease (HSCR) is characterized by an absence
      of ganglion cells in the distal hindgut, extending from the rectum to a variable
      distance proximally, and results from a failure of cranial-caudal neural crest
      cell migration. Hirschsprung's-associated enterocolitis (HAEC) is a condition
      with classic manifestations that include abdominal distention, fever and foul
      smelling stools, and is a significant and life-threatening complication of HSCR.
      The purpose of this review was to critically evaluate recent findings regarding
      the pathophysiology of HAEC. RECENT FINDINGS: Several recent studies have
      investigated the cause of HAEC in humans and mouse models. These studies suggest
      that alterations in the intestinal barrier, including goblet cell number and
      function, and Paneth cell function, impaired gastrointestinal mucosal immunity,
      including B-lymphocyte trafficking or function and secretory immunoglobulin A
      production, and dysbiosis of the intestinal microbiota may contribute to the
      development of HAEC. SUMMARY: Recent studies add to the body of literature,
      suggesting that the intestinal defects observed in HSCR are not restricted to the
      aganglionic segment but extend to the mucosal immune system within and beyond the
      gastrointestinal tract. Future studies further dissecting the mechanisms of HAEC
      and validating these findings in humans will allow for the development of
      directed therapeutic interventions.

PMID- 25944308
TI  - Febrile seizures: emergency medicine perspective.
AB  - PURPOSE OF REVIEW: The review describes current evidence on the evaluation of
      febrile seizures in the acute setting, the need for further outpatient
      assessment, and predictors regarding long-term outcomes of these patients. RECENT
      FINDINGS: New evidence has been added in support of limited assessment and
      intervention: evidence on low utility of lumbar puncture, emergent neuroimaging,
      and follow-up electroencephalography, as well as low yield for antipyretic
      prophylaxis and intermittent use of antiepileptic drugs. Finally, there is
      growing evidence regarding the genetic basis of both febrile seizures and vaccine
      related seizures/febrile seizures. SUMMARY: Routine diagnostic testing for simple
      febrile seizures is being discouraged, and clear evidence-based guidelines
      regarding complex febrile seizures are lacking. Thus, clinical acumen remains the
      most important tool for identifying children with seizures who are candidates for
      a more elaborate diagnostic evaluation. Similarly, evidence and guidelines
      regarding candidates for an emergent out-of-hospital diazepam treatment are
      lacking.

PMID- 25944309
TI  - Update on bariatric surgery in adolescence.
AB  - PURPOSE OF REVIEW: Recent evidence highlighting the prevalence of severe obesity
      in the pediatric population, coupled with disappointing outcomes related to
      medical weight loss interventions, has led to increased interest in bariatric
      surgery. This article focuses on recent additions to the literature regarding the
      current indications and outcomes of adolescent bariatric surgery, emerging
      guidelines on the development of surgical weight loss programs and the status of
      access to bariatric surgical care for adolescents in the United States. RECENT
      FINDINGS: Current data have shown a steady rise in the use of bariatric surgery
      among adolescents and serve to highlight the prevalence of several important
      obesity-related comorbidities. In addition to reports showing the safety and
      efficacy of adolescent bariatric surgery, a number of investigators have
      demonstrated significant improvement in key physiological and metabolic
      parameters (i.e., glucose metabolism, elevated blood pressure, dyslipidemia,
      etc.), offering updated consensus-driven guidelines for the indications for
      surgical intervention, as well as the development of multidisciplinary adolescent
      specific care. Despite favorable outcomes, a disparity exists between the
      pediatric and adult populations related to access to such care. SUMMARY: In
      contrast to previous small and mostly retrospective series, contemporary studies
      have shown that adolescent bariatric surgery is well tolerated and effective.
      Despite these findings and the emergence of a national consensus regarding
      multidisciplinary care, skepticism among primary care providers, as well as
      significant challenges related to healthcare access, remain. Longitudinal studies
      and open dialogue within the medical community are needed.

PMID- 25944311
TI  - Sleep medicine: pediatric polysomnography revisited.
AB  - PURPOSE OF REVIEW: Sleep medicine is an increasingly well subscribed component of
      pediatric medicine. While knowledge has increased significantly in the past five
      decades, whether the most widely used tool to assess sleep-disordered breathing
      possesses demonstrable clinical utility remains unknown. The absence of certainty
      surrounding the impact of polysomnography (PSG) testing on clinical outcomes,
      superimposed on the cost and inconvenience of PSG testing, prompts a call to
      reassess the current normative stance toward PSG testing. RECENT FINDINGS: The
      present study argues for the use of the following: endpoints that have known
      clinical significance; readily available data provided by parents; and data
      derived from a randomized, placebo-controlled trial to determine the merits of
      PSG testing in the context of obstructive sleep apnea. SUMMARY: By rationalizing
      the use PSG testing, cost, inconvenience, and parental anxiety can be decreased
      without compromising care.

PMID- 25944310
TI  - Recent advances in the pathogenesis and management of biliary atresia.
AB  - PURPOSE OF REVIEW: The purpose of this study is to review advances in both the
      pathogenesis and clinical management of biliary atresia. RECENT FINDINGS:
      Immunologic studies have further characterized roles of helper T-cells, B-cells,
      and natural killer cells in the immune dysregulation following viral replication
      within and damage of biliary epithelium. Prominin-1-expressing portal fibroblasts
      may play an integral role in the biliary fibrosis associated with biliary
      atresia. A number of genetic polymorphisms have been characterized as leading to
      susceptibility for biliary atresia. Postoperative corticosteroid therapy is not
      associated with greater transplant-free survival. Newborn screening may improve
      outcomes of infants with biliary atresia and may also provide a long-term cost
      benefit. SUMMARY: Although recent advances have enhanced our understanding of
      pathogenesis and clinical management, biliary atresia remains a significant
      challenge requiring further investigation.

PMID- 25944312
TI  - Gastroparesis in children.
AB  - PURPOSE OF REVIEW: Gastroparesis is a disorder with delayed gastric emptying in
      the absence of mechanical obstruction. It is one of the more common dysmotilities
      that occur in the gastrointestinal tract, and is thought to primarily affect
      adults. Pediatric cases of gastroparesis were considered rare; however, recent
      evidence suggests growing recognition in children and adolescents. Therefore, it
      is important for the pediatric caregiver to understand the condition and the
      treatment options available. RECENT FINDINGS: The majority of patients are women,
      and presentation is usually with symptoms of persistent nausea, emesis,
      postprandial pain and bloating, and early satiety. Weight loss may occur in some
      cases, though this is not universal. The majority of cases are idiopathic, with
      diabetes mellitus the second most common cause. SUMMARY: Treatment consists of
      symptomatic relief with medication to counteract the nausea, emesis, pain,
      bloating, gastroesophageal reflux, early satiety, and improve gastric emptying.
      Dietary modification is also used with small meals and avoidance of high fiber
      and fat-containing foods. Recalcitrant cases of gastroparesis require the use of
      additional approaches such as jejunal feeds, intrapyloric botulinum toxin,
      gastric emptying procedures such as pyloroplasty, and gastric electrical
      stimulation. We will review these options in this article.

PMID- 25944313
TI  - Sleep medicine.
AB  - PURPOSE OF REVIEW: To reflect the recent advances in the field of pediatric sleep
      medicine. The pediatrician will be able to define which children to refer for a
      sleep study and what to expect from the sleep specialist in 2015. RECENT
      FINDINGS: In the first study that compared adeno tonsillectomy (TA) to watchful
      waiting, TA reduced symptoms and improved children's behavior, quality of life,
      and polysomnographic results. Anti-inflammatory therapy for mild obstructive
      sleep apnea was effective and well tolerated according to a double-blind study. A
      retrospective study showed that it is beneficial for 80% of the patients. TA is
      associated with a decrease in asthma symptoms and medication utilization.
      SUMMARY: Pediatricians need to be aware of the clear benefits of tonsillectomy
      (including better asthma control), although anti-inflammatory therapy may improve
      symptoms and polysomnographic findings in children with nonsevere obstructive
      sleep apnea.

PMID- 25944314
TI  - Progress in pediatric pulmonary medicine: incremental and exponential.

PMID- 25944315
TI  - Rapid decrease in length of stay in institutional care for older people in Sweden
      between 2006 and 2012: results from a population-based study.
AB  - There is limited knowledge about older people's length of stay (time until death)
      in institutional care and how it has changed over time. The aim of this study was
      to analyse changes in the length of stay for older people in institutional care
      between 2006 and 2012. All persons 65+ living in Kungsholmen (an urban area of
      Stockholm), who moved to an institution between 2006 and 2012, were included (N =
      1103). The data source was the care system part of a longitudinal database, the
      Swedish National Study on Aging and Care. The average length of stay was analysed
      using Laplace regression for the 10th to the 50th percentile for the years 2006
      2012. The regressions showed that in 2006, it took an average of 764 days before
      50% of those who had moved into institutional care had died. The corresponding
      figure for 2012 was 595 days, which amounts to a 22.1% decrease over the period
      studied (P = 0.078). For the lower percentiles, the decrease was even more rapid,
      for example for the 30th percentile, the length of stay reduced from 335 days in
      2006 to 119 days in 2012, a decrease of 64.3% (P < 0.001). The most rapid
      increase was found in the proportion that moved to an institution and died within
      a short time period. In 2006, the first 10% had on average died after 85 days, in
      2012 after only 8 days; a decrease in the length of stay of 90.5% (P = 0.002). In
      general, there was a significant decrease in the length of stay in institutional
      care between 2006 and 2012. The most dramatic change over the period studied was
      an increase in the proportion of people who moved into an institution and died
      shortly afterwards.

PMID- 25944316
TI  - Solicitude: balancing compassion and empowerment in a relational ethics of hope
      an empirical-ethical study in palliative care.
AB  - The ethics of hope has often been understood as a conflict between duties: do not
      lie versus do not destroy hope. However, such a way of framing the ethics of hope
      may easily place healthcare professionals at the side of realism and patients at
      the side of (false) hope. That leaves unexamined relational dimensions of hope.
      The objective of this study was to describe a relational ethics of hope based on
      the perspectives of palliative care patients, their family members and their
      healthcare professionals. A qualitative longitudinal method based on narrative
      theories was used. Semi-structured interviews on hope were conducted with twenty
      nine palliative care patients, nineteen friends or family members, and fifty-two
      healthcare professionals, which were recorded and transcribed. Data on hope were
      thematically analyzed. The researchers wrote memos and did member checking with
      participants. When participants spoke about hope, they referred to power and
      empowerment, like the powerful bonding of hope between patients and physicians.
      They also associated hope with the loss of hope and suffering. Several
      participating healthcare professionals tried to balance both sides, which
      involved acknowledgment of hope and suffering. Hope and power were reflected in
      the ethical concept of empowerment, whereas suffering and the loss of hope were
      reflected in the ethical concept of compassion. Empowerment and compassion can be
      balanced in solicitude. In conclusion, a relational ethics of hope requires
      solicitude, in which healthcare professionals are able to weigh empowerment and
      compassion within particular relationships. 

PMID- 25944317
TI  - The N-terminal cytoplasmic domain of neuregulin 1 type III is intrinsically
      disordered.
AB  - Axonally expressed neuregulin 1 (NRG1) type III is a transmembrane protein
      involved in various neurodevelopmental processes, including myelination and
      Schwann cell migration. NRG1 type III has one transmembrane domain and a C
      terminal extracellular segment, which contains an epidermal growth factor
      homology domain. Little is known, however, about the intracellular N terminus of
      NRG1 type III, and the structure-function relationships of this cytoplasmic
      domain have remained uncharacterized. In the current study, we carried out the
      first structural and functional studies on the NRG1 type III cytoplasmic domain.
      Based on sequence analyses, the domain is predicted to be largely disordered,
      while a strictly conserved region close to the transmembrane segment may contain
      helical structure and bind metal ions. As shown by synchrotron radiation circular
      dichroism spectroscopy, the recombinant NRG1 type III cytoplasmic domain was
      disordered in solution, but it was able to fold partially into a helical
      structure, especially when both metals and membrane-mimicking compounds were
      present. NRG1 cytoplasmic tail binding to metals was further confirmed by
      calorimetry. These results suggest that the juxtamembrane segment of the NRG1
      type III cytoplasmic domain may fold onto the membrane surface upon metal
      binding. Using synchrotron small-angle X-ray scattering, we further proved that
      the NRG1 cytoplasmic domain is intrinsically disordered, highly elongated, and
      behaves like a random polymer. Our work provides the first biochemical and
      biophysical data on the previously unexplored cytoplasmic domain of NRG1 type
      III, which will help elucidate the detailed structure-function relationships of
      this domain. 

PMID- 25944318
TI  - Soluble biomarkers of immune activation and inflammation in HIV infection: impact
      of 2 years of effective first-line combination antiretroviral therapy.
AB  - OBJECTIVES: The aim of the study was to assess the impact of rapid and sustained
      viral control produced by combination antiretroviral therapy (cART) on HIV
      associated immune activation and inflammation. METHODS: In this longitudinal
      observational study, we examined changes in interleukin-6 (IL-6), interferon
      gamma-inducible protein-10 (IP-10), monokine induced by interferon-gamma (MIG)
      and soluble CD14 (sCD14) levels during 2 years of effective first-line cART.
      Biomarker levels before and after cART were compared with those observed in
      healthy subjects, using the Wilcoxon signed rank test. Elevated biomarker levels
      were defined with respect to values for healthy subject (mean + 2 standard
      deviations). Factors associated with persistently elevated biomarker levels after
      2 years of cART were identified by logistic regression. RESULTS: We included in
      the study 139 patients with a median HIV-1 RNA level of 4.8 log10 HIV-1 RNA
      copies/mL and a median CD4 cell count of 294 cells/MUL at cART initiation [day 0
      (D0)]. At D0, all biomarker levels were higher than in healthy subjects (P <
      0.05). After 2 years of cART, IL-6, IP-10 and MIG levels fell significantly, by a
      median of 0.54, 420 and 1107 pg/mL, respectively (all P < 0.001), and were no
      longer elevated in > 75% of patients. In contrast, sCD14 levels did not change
      significantly (0.18 * 10(6)  pg/mL; P = 0.102) and remained elevated. Older age
      was associated with elevated levels of IP-10 [odds ratio (OR) 1.60 per 10 years
      older; P = 0.047] and MIG (OR 1.92 per 10 years older; P = 0.007) after 2 years
      of cART. CONCLUSIONS: The rapid and sustained viral suppression produced by first
      line cART reduced IL-6, IP-10 and MIG to normal levels, while sCD14, a marker of
      monocyte activation, remained elevated. High levels of IP-10 and MIG tended to
      persist in older patients.

PMID- 25944319
TI  - Role of imaging in current acute ischemic stroke workflow for endovascular
      therapy.
AB  - Ischemic stroke is caused by a thrombus that blocks an intracranial artery. Brain
      tissue beyond the blocked artery survives for a variable period of time because
      of blood and nutrients received through tiny vessels called collaterals. Imaging
      the brain and the vasculature that supplies it is therefore a vital first step in
      treating patients with acute ischemic stroke. In this review, we focus on current
      evidence for imaging selection of patients for endovascular therapy in the
      context of the recently positive clinical trials, such as Multicenter Randomized
      Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the
      Netherlands (MR CLEAN), Endovascular Treatment for Small Core and Anterior
      Circulation Proximal Occlusion With Emphasis on Minimizing Computed Tomography to
      Recanalization Times (ESCAPE), Solitaire With the Intention for Thrombectomy as
      Primary Endovascular Treatment (SWIFT PRIME), and Extending the Time for
      Thrombolysis in Emergency Neurological Deficits-Intra-Arterial (EXTEND-IA). We
      discuss evidence for and use of the various imaging paradigms available. We
      discuss how to set up quick and efficient imaging protocols for patient selection
      and address common concerns about the use of imaging, including time spent,
      contrast, radiation, and other advantages and disadvantages. Finally, we briefly
      comment on how imaging can integrate itself within various health systems of care
      in the future, thereby potentially improving patient outcomes further. 

PMID- 25944320
TI  - Obesity increases risk of ischemic stroke in young adults.
AB  - BACKGROUND AND PURPOSE: Body mass index has been associated with ischemic stroke
      in older populations, but its association with stroke in younger populations is
      not known. In light of the current obesity epidemic in the United States, the
      potential impact of obesity on stroke risk in young adults deserves attention.
      METHODS: A population-based case-control study design with 1201 cases and 1154
      controls was used to investigate the relationship of obesity and young onset
      ischemic stroke. Stroke cases were between the ages of 15 and 49 years. Logistic
      regression analysis was used to evaluate the association between body mass index
      and ischemic stroke with and without adjustment for comorbid conditions
      associated with stroke. RESULTS: In analyses adjusted for age, sex, and
      ethnicity, obesity (body mass index >30 kg/m(2)) was associated with an increased
      stroke risk (odds ratio, 1.57; 95% confidence interval, 1.28-1.94) although this
      increased risk was highly attenuated and not statistically significant after
      adjustment for smoking, hypertension, and diabetes mellitus. CONCLUSIONS: These
      results indicate that obesity is a risk factor for young onset ischemic stroke
      and suggest that this association may be partially mediated through hypertension,
      diabetes mellitus, or other variables associated with these conditions.

PMID- 25944321
TI  - Obesity increases stroke risk in young adults: opportunity for prevention.

PMID- 25944322
TI  - Acute reperfusion therapy and stroke care in Asia after successful endovascular
      trials.
AB  - The current status of and prospects for acute stroke care in Asia in the
      situation where both intravenous thrombolysis and endovascular therapies have
      been recognized as established strategies for acute stroke are reviewed. Of 15
      million people annually having stroke worldwide, ~9 million are Asians. The
      burdens of both ischemic and hemorrhagic strokes are severe in Asia. The unique
      features of stroke in Asia include susceptibility to intracranial
      atherosclerosis, high prevalence of intracerebral hemorrhage, effects of dietary
      and lifestyle habits, and several disorders with genetic causes. These features
      affect acute stroke care, such as the dosage of alteplase for thrombolysis and
      consideration of bleeding complications during antithrombotic therapy. Acute
      endovascular thrombectomy, as well as intravenous thrombolysis, is relatively
      prevalent in East Asia, but most of the other Asian countries need to develop
      their human resources and fundamental medical infrastructure for stroke care. A
      limitation of endovascular therapy in East Asia is the high prevalence of
      intracranial atherosclerosis that can cause recanalization failure and require
      additional angioplasty or permanent stent insertion although intracranial
      stenting is not an established strategy. Multinational collaboration on stroke
      research among Asian countries is infrequent. Asians should collaborate to
      perform their own thrombolytic and endovascular trials and seek the optimal
      strategy for stroke care specific to Asia. 

PMID- 25944323
TI  - Edema Extension Distance: Outcome Measure for Phase II Clinical Trials Targeting
      Edema After Intracerebral Hemorrhage.

PMID- 25944324
TI  - Dawning of a new era for acute stroke therapy.

PMID- 25944326
TI  - Implication of the recent positive endovascular intervention trials for
      organizing acute stroke care: European perspective.
AB  - Timely recanalization leads to improved patient outcomes in acute ischemic
      stroke. Recent trial results demonstrated a strong benefit for endovascular
      therapies over standard medical care in patients with acute ischemic stroke and a
      major intracranial artery occlusion<=6 hours or even beyond from symptom onset
      and independent of patients' age. Previous studies have shown the benefit of
      intravenous thrombolysis that had gradually, albeit slowly, reshaped acute stroke
      care worldwide. Now, given the superior benefits of endovascular intervention,
      the whole structure of acute stroke care needs to be reorganized to meet patient
      needs and to deliver evidence-based treatments effectively. However, a blueprint
      for success with novel stroke treatments should be composed of numerous elements
      and requires efforts from various parties. Regarding the endovascular therapies,
      the strengths of Europe include highly organized democratic society structures,
      high rate of urbanization, well-developed revenue-based healthcare systems, and
      high income levels, whereas the obstacles include the east-west disparity in
      wealth, the ongoing economic crisis hindering spread of fairly costly new
      treatments, and the quickly aging population putting more demands on health care
      in general. Regional and national plans for covering whole population with 24/7
      adequate acute stroke care are necessary in close cooperation of professionals
      and decision-makers. Europe-wide new training programs for expert physicians in
      stroke care should be initiated shortly. European Stroke Organisation has a
      unique role in providing expertise, consultation, guidelines, and versatile
      training in meeting new demands in stroke care. This article discusses the
      current situation, prospects, and challenges in Europe offering personal views on
      potential solutions.

PMID- 25944325
TI  - State of acute endovascular therapy: report from the 12th thrombolysis,
      thrombectomy, and acute stroke therapy conference.

PMID- 25944327
TI  - Interventionalist perspective on the new endovascular trials.
AB  - Three recently published trials have conclusively proven the benefit of
      mechanical endovascular thrombectomy over best medical therapy for patients with
      acute ischemic stroke and large vessel occlusion. These trials shared some
      features and differed in others. These similarities and differences in trial
      design and execution affect the conclusions and recommendations that can be made
      from the data. We will examine the implications of these studies for
      neurointerventionists, both for current practice and for future studies. In
      particular, we will focus on procedural details such as patient selection,
      devices, adjunctive therapies, treatment time windows, and performance metrics. 

PMID- 25944328
TI  - Stroke Neurologist's Perspective on the New Endovascular Trials.
AB  - Before December 2014, the only proven effective treatment for acute ischemic
      stroke was recombinant tissue-type plasminogen activator (r-tPA). This has now
      changed with the publication of the Multicenter Randomized Clinical Trial of
      Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN),
      Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion
      With Emphasis on Minimizing CT to Recanalization Times (ESCAPE), Extending the
      Time for Thrombolysis in Emergency Neurological Deficits--Intra-Arterial (EXTEND
      IA), Solitaire With the Intention for Thrombectomy as Primary Endovascular
      Treatment Trial (SWIFT PRIME), and Randomized Trial of Revascularization With the
      Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke
      Due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours
      of Symptom Onset (REVASCAT) studies. We review the main results of these studies
      and how they inform stroke patient management going forward. The main take home
      points for neurologists are (1) intra-arterial thrombectomy is a potently
      effective treatment and should be offered to patients who have documented
      occlusion in the distal internal carotid or the proximal middle cerebral artery,
      have a relatively normal noncontrast head computed tomographic scan, severe
      neurological deficit, and can have intra-arterial thrombectomy within 6 hours of
      last seen normal; (2) benefits are clear in patients receiving r-tPA before intra
      arterial thrombectomy; r-tPA should not be withheld if the patient meets
      criteria, and benefit in patients who do not receive r-tPA or have r-tPA
      exclusions requires further study; and (3) these favorable results occur when
      intra-arterial thrombectomy is performed in an endovascular stroke center by a
      coordinated multidisciplinary team that extends from the prehospital stage to the
      endovascular suite, minimizes time to recanalization, uses stent-retriever
      devices, and avoids general anesthesia. In conclusion, stroke teams, including
      practicing neurologists caring for patients with stroke should now provide the
      option for intra-arterial thrombectomy for a subset of patients with acute
      stroke.

PMID- 25944330
TI  - Endovascular clot retrieval therapy: implications for the organization of stroke
      systems of care in North America.
AB  - Endovascular acute ischemic stroke therapy is now proven by randomized controlled
      trials to produce large, clinically meaningful benefits. In response, stroke
      systems of care must change to increase timely and equitable access to this
      therapy. In this review, we provide a North American perspective on implications
      for stroke systems, focusing on the United States and Canada, accompanied by
      initial recommendations for changes. Most urgently, every community must create
      access to a hospital that can safely and quickly provide intravenous tissue-type
      plasminogen activator and immediately transfer appropriate patients onward to a
      more capable center as required. Safe and effective therapy in the community
      setting will be ensured by certification programs, performance measurement, and
      data entry into registries. 

PMID- 25944331
TI  - Is visual evaluation of aneurysm coiling a reliable study end point? Systematic
      review and meta-analysis.
AB  - BACKGROUND AND PURPOSE: Angiographic occlusion as a surrogate marker of
      satisfactory aneurysm treatment is commonly used in clinical trials although some
      pitfalls have to be considered. To investigate the inter-rater reliability of
      visual rating of aneurysm occlusion as study end point, we performed a systematic
      review and meta-analysis. METHODS: Electronic databases (MEDLINE, EMBASE, PubMed,
      and the Cochrane Library) were searched up to June 2014. Assessment of risk for
      bias was based on the Quality Appraisal Tool for Studies of Diagnostic
      Reliability and the Guidelines for Reporting Reliability and Agreement studies.
      Inter-rater reliability estimates were pooled across studies using meta-analysis,
      and the influence of several factors (eg, imaging methods, grading scales, and
      occlusion rate) was tested with meta-regression. RESULTS: From 1193 titles, 644
      abstracts and 87 full-text versions were reviewed. Twenty-six articles met the
      inclusion criteria and provided 77 reliability estimates. Twenty-one different
      rating scales were used, and statistical analysis varied. Mean inter-rater
      agreement of the pooled studies was substantial (kappa=0.65; 95% confidence
      interval, 0.60-0.69). Reliability varied significantly as a function of imaging
      methods, grading scales, occlusion rates, and their interaction. Observer
      agreement substantially increased with increasing occlusion rate in digital
      subtraction angiography but not in MR angiography. Reliability was higher in
      studies using 2- or 3-value grading scales than in studies with 4-value grading
      scales. CONCLUSIONS: There is significant heterogeneity between studies
      evaluating the reliability of visual evaluation of aneurysm coiling. On the basis
      of our analysis, we found that the combination of magnetic resonance angiography,
      3-value grading scale, and 2 trained raters seems most promising for usage as
      surrogate study end points.

PMID- 25944329
TI  - Minocycline reduces spontaneous hemorrhage in mouse models of cerebral amyloid
      angiopathy.
AB  - BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy (CAA) is a common cause of
      recurrent intracerebral hemorrhage in the elderly. Previous studies have shown
      that CAA induces inflammation and expression of matrix metalloproteinase-2 and
      matrix metalloproteinase-9 (gelatinases) in amyloid-laden vessels. Here, we
      inhibited both using minocycline in CAA mouse models to determine whether
      spontaneous intracerebral hemorrhage could be reduced. METHODS: Tg2576 (n=16) and
      5xFAD/ApoE4 knockin mice (n=16), aged 17 and 12 months, respectively, were
      treated with minocycline (50 mg/kg, IP) or saline every other day for 2 months.
      Brains were extracted and stained with X-34 (to quantify amyloid), Perls' blue
      (to quantify hemorrhage), and immunostained to examined beta-amyloid peptide
      load, gliosis (glial fibrillary acidic protein [GFAP], Iba-1), and vascular
      markers of blood-brain barrier integrity (zonula occludins-1 [ZO-1] and collagen
      IV). Brain extracts were used to quantify mRNA for a variety of inflammatory
      genes. RESULTS: Minocycline treatment significantly reduced hemorrhage frequency
      in the brains of Tg2576 and 5xFAD/ApoE4 mice relative to the saline-treated mice,
      without affecting CAA load. Gliosis (GFAP and Iba-1 immunostaining), gelatinase
      activity, and expression of a variety of inflammatory genes (matrix
      metalloproteinase-9, NOX4, CD45, S-100b, and Iba-1) were also significantly
      reduced. Higher levels of microvascular tight junction and basal lamina proteins
      were found in the brains of minocycline-treated Tg2576 mice relative to saline
      treated controls. CONCLUSIONS: Minocycline reduced gliosis, inflammatory gene
      expression, gelatinase activity, and spontaneous hemorrhage in 2 different mouse
      models of CAA, supporting the importance of matrix metalloproteinase-related and
      inflammatory pathways in intracerebral hemorrhage pathogenesis. As a Food and
      Drug Administration-approved drug, minocycline might be considered for clinical
      trials to test efficacy in preventing CAA-related intracerebral hemorrhage.

PMID- 25944332
TI  - A cross-sectional survey of optometrists and optometric practices in Ghana.
AB  - PURPOSE: The study was conducted to profile optometrists and optometric practices
      in Ghana. METHODS: An online survey was conducted among 146 optometrists, who
      were registered with the Ghana Optometric Association (GOA). It included
      questions on their demographics, equipment, ophthalmic procedures routinely
      conducted and the barriers to providing a full scope of optometric services.
      RESULTS: Ninety registered optometrists (62 per cent) responded, their mean age
      being 28.97 +/- 3.36 years. There were more males (68.9 per cent) than females
      and most had the Doctor of Optometry (OD) degree, the profession's highest degree
      in Ghana. There were more practitioners in urban centres (71.1 per cent) and most
      practices had basic optometric instruments, such as direct ophthalmoscopes,
      slitlamp biomicroscopes and retinoscopes. Many optometrists routinely conducted
      direct ophthalmoscopy (100 per cent), slitlamp biomicroscopy (87.5 per cent) and
      contact tonometry (55.7 per cent); however, few provided contact lens (10.2 per
      cent) and low vision (9.1 per cent) assessments, with 76 per cent stating that it
      was due to the unavailability of low vision devices, poor sources of contact
      lenses (27 per cent) and perceived insufficient training (11.2 per cent). Many
      practitioners (97 per cent) reported the use of diagnostic pharmaceutical agents
      and therapeutic pharmaceutical agents (96.6 per cent). Most practitioners (52.9
      per cent) preferred conferences for the delivery of continuous professional
      development over publications (26.4 per cent) and internet resources (12.6 per
      cent). CONCLUSION: The data elicited in this study provide a basis for addressing
      the country's unmet eye-care needs and can be used to determine training and
      support guidelines for the profession.

PMID- 25944333
TI  - Measuring body composition: the limitations of body mass index.

PMID- 25944334
TI  - Editorial: Thematic issue: infectious diseases seldom discriminate.

PMID- 25944335
TI  - Current status of trachoma elimination in Australia: making trachoma a history by
      2020.
AB  - Trachoma is one of the major causes of preventable blindness worldwide. In
      Australia it is solely a disease of Aboriginal people. Trachoma in non-indigenous
      Australians has been eradicated earlier this century, however, is still prevalent
      among Aboriginal communities. Poor living condition, lack of access to water
      supply and sanitation, living in a crowded and unhealthy environment are the main
      causes of trachoma in Indigenous Australians. The World Health Organization (WHO)
      has initiated Global Alliance for the Elimination of Trachoma by the year 2020
      (GET2020). The alliance has adopted the "SAFE" (Surgery, Antibiotic distribution,
      Facial cleanliness and Environmental improvements) strategy to eliminate trachoma
      in endemic countries. In Australia, the National Trachoma Surveillance and
      Reporting Unit (NTSRU) was established in 2006 and ever since has been providing
      high quality surveillance data on national trachoma burden. In 2009, the
      Australian Government made a commitment investment of $16 million over a 4-year
      period to eliminate trachoma from Australia. Today, promising success has been
      achieved in surveillance and management of trachoma using the SAFE strategy. But
      the ultimate elimination of the disease would require a long-term political
      commitment founded, inter alia, on multi-sectoral collaboration, targeted
      research, and community engagement. 

PMID- 25944337
TI  - Scaling Cognitive Domains of the Montreal Cognitive Assessment: An Analysis Using
      the Partial Credit Model.
AB  - The psychometric properties of the Montreal Cognitive Assessment (MoCA) were
      examined by using the Partial Credit Model. The study sample included 897
      participants who were distributed into two main subgroups: (I) the clinical group
      (90 patients with Mild Cognitive Impairment, 90 patients with Alzheimer's
      disease, 33 patients with Frontotemporal Dementia, and 34 patients with Vascular
      dementia, whose diagnoses were previously established according to a consensus
      that was reached by a multidisciplinary team, based on the international
      criteria) and (II) the healthy group (composed of 650 cognitively healthy
      community dwellers). The results show (i) an overall good fit for both the items
      and the persons' values, (ii) high variability for the cognitive performance
      level of the cognitive domains (ranging between 1.90 and -3.35, where "Short-term
      Memory" was the most difficult item and "Spatial Orientation" was the easiest
      item) and between the subjects on the scale, (iii) high reliability for the
      estimation of the persons' values, (iv) good discriminant validity and high
      diagnostic utility, and (v) a minimal differential item functioning effect
      related to of pathology, gender, age, and educational level. MoCA and its
      cognitive domains are suitable measures to use for screening the cognitive status
      of cognitively healthy subjects and patients with cognitive impairment. 

PMID- 25944336
TI  - High-recovery visual identification and single-cell retrieval of circulating
      tumor cells for genomic analysis using a dual-technology platform integrated with
      automated immunofluorescence staining.
AB  - BACKGROUND: Circulating tumor cells (CTCs) are malignant cells that have migrated
      from solid cancers into the blood, where they are typically present in rare
      numbers. There is great interest in using CTCs to monitor response to therapies,
      to identify clinically actionable biomarkers, and to provide a non-invasive
      window on the molecular state of a tumor. Here we characterize the performance of
      the AccuCyte(r)--CyteFinder(r) system, a comprehensive, reproducible and highly
      sensitive platform for collecting, identifying and retrieving individual CTCs
      from microscopic slides for molecular analysis after automated immunofluorescence
      staining for epithelial markers. METHODS: All experiments employed a density
      based cell separation apparatus (AccuCyte) to separate nucleated cells from the
      blood and transfer them to microscopic slides. After staining, the slides were
      imaged using a digital scanning microscope (CyteFinder). Precisely counted model
      CTCs (mCTCs) from four cancer cell lines were spiked into whole blood to
      determine recovery rates. Individual mCTCs were removed from slides using a
      single-cell retrieval device (CytePickerTM) for whole genome amplification and
      subsequent analysis by PCR and Sanger sequencing, whole exome sequencing, or
      array-based comparative genomic hybridization. Clinical CTCs were evaluated in
      blood samples from patients with different cancers in comparison with the
      CellSearch(r) system. RESULTS: AccuCyte--CyteFinder presented high-resolution
      images that allowed identification of mCTCs by morphologic and phenotypic
      features. Spike-in mCTC recoveries were between 90 and 91%. More than 80% of
      single-digit spike-in mCTCs were identified and even a single cell in 7.5 mL
      could be found. Analysis of single SKBR3 mCTCs identified presence of a known
      TP53 mutation by both PCR and whole exome sequencing, and confirmed the reported
      karyotype of this cell line. Patient sample CTC counts matched or exceeded
      CellSearch CTC counts in a small feasibility cohort. CONCLUSION: The AccuCyte-
      CyteFinder system is a comprehensive and sensitive platform for identification
      and characterization of CTCs that has been applied to the assessment of CTCs in
      cancer patient samples as well as the isolation of single cells for genomic
      analysis. It thus enables accurate non-invasive monitoring of CTCs and evolving
      cancer biology for personalized, molecularly-guided cancer treatment.

PMID- 25944338
TI  - Perception of Ethical Misconduct by Neuropsychology Professionals in Latin
      America.
AB  - To date, extremely limited research has focused on the ethical aspects of
      clinical neuropsychology practice in Latin America. The current study aimed to
      identify the frequency of perceived ethical misconduct in a sample of 465 self
      identified neuropsychology professionals from Latin America in order to better
      guide policies for training and begin to establish standards for practitioners in
      the region. Frequencies of neuropsychologists who knew another professional
      engaging in ethical misconduct ranged from 1.1% to 60.4% in the areas of
      research, clinical care, training, and professional relationships. The most
      frequently reported perceived misconduct was in the domain of professional
      training and expertise, with nearly two thirds of participants knowing other
      professionals who do not possess adequate training to be working as
      neuropsychologists. The least frequently reported perceived misconduct was in the
      domain of professional relationships. Nearly one third of participants indicated
      that they had never received formal training in professional ethics. 

PMID- 25944339
TI  - Bhalla P et al (Clin Infect Dis 2015; 60:1068-74).

PMID- 25944340
TI  - Dose-Related Differences in Effectiveness of Human Papillomavirus Vaccination
      Against Genital Warts: A Nationwide Study of 550,000 Young Girls.
AB  - BACKGROUND: Reducing the number of doses in the human papillomavirus (HPV)
      vaccination regimen from 3 to 2 could increase coverage rates. In this cohort
      study, we assessed the risk of genital warts (GWs) according to timing and number
      of doses of quadrivalent HPV vaccine. METHODS: From population-based registries,
      we identified all girls in Denmark born during 1985-1999, for whom information on
      HPV vaccinations was retrieved. The cohort was followed for GW occurrence during
      2006-2012. Incidence rate ratios (IRRs) were calculated by Poisson regression to
      determine differences in GW rates by number of vaccine doses. RESULTS: Of the
      550,690 girls in the cohort, 361 734 had been vaccinated. Of these, 25.9% had
      been vaccinated twice and 58.8% 3 times. The risk of GWs decreased significantly
      with each additional dose of vaccine. For girls who received 2 doses, extension
      of the interval between doses reduced the incidence of GWs. In comparison with a
      2-month interval, the incidence of GWs was reduced by 45% (95% confidence
      interval [CI], 20%-62%), 55% (95% CI, 35%-69%), and 63% (95% CI, 44%-75%), with
      an interval of 4, 5, and 6 months, respectively. The IRR of 2 vs 3 doses was
      close to 1, with an interval of about 6 months between the first 2 doses.
      CONCLUSIONS: With the original vaccine schedule, completion of 3 doses seems to
      be required to obtain full protection against GWs. A 2-dose regimen may be as
      effective if the dosing interval is extended to around 6 months, although the
      long-term effectiveness of this regimen is unknown.

PMID- 25944341
TI  - Reply to Bauer and Goff.

PMID- 25944342
TI  - Escherichia Coli Meningitis Features in 325 Children From 2001 to 2013 in France.
AB  - BACKGROUND: We aimed to describe features of Escherichia coli meningitis in a
      large population of children and the molecular characteristics of the involved
      strains to determine factors associated with severe disease or death. METHODS:
      Between 2001 and 2013, a prospective national survey collected data for 325
      children hospitalized with E. coli meningitis. The national reference center
      genetically characterized 141 isolates. RESULTS: Among the 325 cases, 65.2% were
      term, 22.4% late preterm, and 12.5% very/extremely preterm infants. Escherichia
      coli meningitis was 7-fold more frequent in preterm than term infants. Median age
      at diagnosis was 14 days; 71.1% of infants were neonates, with 2 peaks of
      infection at age 0-3 days (mostly preterm neonates) and 11-15 days (mostly term
      neonates); 8.9% were >89 days old. In total, 51.1% patients were considered to
      have severe disease, and 9.2% died. B2.1 phylogenetic subgroup (56%) and O1
      serogroup (27.7%) were the most frequently identified. On multivariate analysis,
      death was associated with preterm birth (odds ratio [OR], 3.3 [95% confidence
      interval {CI}, 1.3-8.4], P = .015 for late preterm infants; OR, 7.3 [95% CI, 2.7
      20.9], P < .001 for very/extremely preterm infants) and cerebrospinal fluid (CSF)
      to blood glucose ratio <0.10 (OR, 15.3 [95% CI, 1.8-128.3], P = .012). Death was
      associated with uncommon O serogroup strains (P = .014) and severe disease with
      O7 serogroup (P = .034) and PapGII adhesin (OR, 2.3 [95% CI, 1.2-4.5], P = .015).
      CONCLUSIONS: In this large study of 325 cases of E. coli meningitis, risk factors
      of severe disease or death were preterm birth, severe hypoglycorrhachia,
      CSF/blood glucose ratio <0.10, and molecular characteristics of strains, which
      should help optimize therapeutic management.

PMID- 25944343
TI  - When diagnostic technology is ahead of the hospital budget: what is antimicrobial
      stewardship to do?

PMID- 25944344
TI  - Raltegravir in HIV-1-Infected Pregnant Women: Pharmacokinetics, Safety, and
      Efficacy.
AB  - BACKGROUND: The use of raltegravir in human immunodeficiency virus (HIV)-infected
      pregnant women is important in the prevention of mother-to-child HIV
      transmission, especially in circumstances when a rapid decline of HIV RNA load is
      warranted or when preferred antiretroviral agents cannot be used. Physiological
      changes during pregnancy can reduce antiretroviral drug exposure. We studied the
      effect of pregnancy on the pharmacokinetics of raltegravir and its safety and
      efficacy in HIV-infected pregnant women. METHODS: An open-label, multicenter,
      phase 4 study in HIV-infected pregnant women receiving raltegravir 400 mg twice
      daily was performed (Pharmacokinetics of Newly Developed Antiretroviral Agents in
      HIV-Infected Pregnant Women Network). Steady-state pharmacokinetic profiles were
      obtained in the third trimester and postpartum along with cord and maternal
      delivery concentrations. Safety and virologic efficacy were evaluated. RESULTS:
      Twenty-two patients were included, of which 68% started raltegravir during
      pregnancy. Approaching delivery, 86% of the patients had an undetectable viral
      load (<50 copies/mL). None of the children were HIV-infected. Exposure to
      raltegravir was highly variable. Overall area under the plasma concentration-time
      curve (AUC) and plasma concentration at 12 hours after intake (C12h) plasma
      concentrations in the third trimester were on average 29% and 36% lower,
      respectively, compared with postpartum: Geometric mean ratios (90% confidence
      interval) were 0.71 (.53-.96) for AUC0-12h and 0.64 (.34-1.22) for C12h. The
      median ratio of raltegravir cord to maternal blood was 1.21 (interquartile range,
      1.02-2.17; n = 9). CONCLUSIONS: Raltegravir was well tolerated during pregnancy.
      The pharmacokinetics of raltegravir showed extensive variability. The observed
      mean decrease in exposure to raltegravir during third trimester compared to
      postpartum is not considered to be of clinical importance. Raltegravir can be
      used in standard dosages in HIV-infected pregnant women. CLINICAL TRIALS
      REGISTRATION: NCT00825929.

PMID- 25944345
TI  - Critical Care Medicine and Infectious Diseases: An Emerging Combined Subspecialty
      in the United States.
AB  - The recent rise in unfilled training positions among infectious diseases (ID)
      fellowship programs nationwide indicates that ID is declining as a career choice
      among internal medicine residency graduates. Supplementing ID training with
      training in critical care medicine (CCM) might be a way to regenerate interest in
      the specialty. Hands-on patient care and higher salaries are obvious attractions.
      High infection prevalence and antibiotic resistance in intensive care units,
      expanding immunosuppressed host populations, and public health crises such as the
      recent Ebola outbreak underscore the potential synergy of CCM-ID training. Most
      intensivists receive training in pulmonary medicine and only 1% of current board
      certified intensivists are trained in ID. While still small, this cohort of CCM
      ID certified physicians has continued to rise over the last 2 decades. ID and CCM
      program leadership nationwide must recognize these trends and the merits of the
      CCM-ID combination to facilitate creation of formal dual-training opportunities. 

PMID- 25944346
TI  - Comparison of consolidation strategies in acute myeloid leukemia: high-dose
      cytarabine alone versus intermediate-dose cytarabine combined with
      anthracyclines.
AB  - We compared the efficacy of high-dose cytarabine alone to that of intermediate
      dose cytarabine combined with anthracyclines as consolidation therapy. Patients
      enrolled in the Korea University acute myeloid leukemia (AML) registry received
      remission induction chemotherapy with the same standard induction regimen
      (idarubicin and cytarabine 3 + 7). Postremission therapy was performed for three
      or four cycles according to one of the following regimens: high-dose cytarabine
      (3 g/m(2)) or combination of intermediate-dose cytarabine (1 g/m(2)) with
      anthracyclines (idarubicin or mitoxantrone). Among the 443 AML patients enrolled
      in the registry, 145 patients received consolidation chemotherapy. The median
      overall survival (OS) and relapse-free survival (RFS) in the high-dose cytarabine
      group were significantly longer than those in the anthracycline combination group
      (OS, not reached vs. 16.6 months, p = 0.045; RFS, 38.6 months vs. 11.0 months, p
      = 0.011). The median duration of neutropenia was longer in the anthracycline
      combination group than in the high-dose cytarabine group (8 vs. 10 days, p =
      0.001). This study suggests that high-dose cytarabine consolidation may produce
      superior outcomes than combination treatment with intermediate-dose cytarabine
      and anthracyclines and that the addition of anthracyclines during AML
      consolidation has limited value as compared to cytarabine intensification. 

PMID- 25944347
TI  - Fatal pulmonary hemorrhage after carfilzomib treatment in multiple myeloma.

PMID- 25944348
TI  - Laryngectomy Complications Are Associated with Perioperative Antibiotic Choice.
AB  - OBJECTIVE: To assess hospital- and physician-level variation in pattern of
      perioperative antibiotic use for laryngectomy and the relationship between
      pattern of antibiotic use and surgical site infection (SSI), wound dehiscence,
      and antibiotic-induced complications. STUDY DESIGN: Retrospective analysis of
      University HealthSystem Consortium data. SETTING: Academic medical centers and
      affiliated hospitals. SUBJECTS AND METHODS: Elective admissions for laryngectomy
      from 2008 to 2011 and associated 30-day readmissions were analyzed with
      multivariate logistic regression models. RESULTS: There were 439 unique
      antibiotic regimens (agents and duration) identified over the first 4 days of the
      1865 admissions included in this study. Ampicillin/sulbactam, cefazolin +
      metronidazole, and clindamycin were the most common agents given on the day of
      surgery. Clindamycin was independently associated with higher odds of SSI (odds
      ratio [OR] = 3.87, 95% confidence interval [CI] = 2.31-6.49]), wound dehiscence
      (OR = 3.42, 95% CI = 2.07-5.64), and antibiotic-induced complications (OR = 3.01,
      95% CI = 1.59-5.67) when given alone; it was also associated with higher odds of
      SSI (OR = 2.69, 95% CI = 1.43-5.05) and antibiotic-induced complications (OR =
      2.20, 95% CI = 1.04-4.64) when given with other agents. These effects were
      stronger in a subsample of high-volume physicians and hospitals. CONCLUSION:
      There is substantial variability in perioperative antibiotic strategies for
      laryngectomy. Clindamycin was associated with much higher odds of short-term
      complications as compared to other common regimens. Based on these data, clinical
      trials should be planned to firmly establish the most effective and cost
      effective antibiotic management for laryngectomy and determine potential
      alternatives to clindamycin for penicillin-allergic patients.

PMID- 25944349
TI  - US insurers are denying women access to care guaranteed by health law, report
      finds.

PMID- 25944350
TI  - Detection of volatile organic compounds indicative of human presence in the air.
AB  - Volatile organic compounds were collected and analyzed from a variety of indoor
      and outdoor air samples to test whether human-derived compounds can be readily
      detected in the air and if they can be associated with human occupancy or
      presence. Compounds were captured with thermal desorption tubes and then analyzed
      by gas chromatography with mass spectrometry. Isoprene, a major volatile organic
      compound in exhaled breath, was shown to be the best indicator of human presence.
      Acetone, another major breath-borne compound, was higher in unoccupied or
      minimally occupied areas than in human-occupied areas, indicating that its
      majority may be derived from exogenous sources. The association of endogenous
      skin-derived compounds with human occupancy was not significant. In contrast,
      numerous compounds that are found in foods and consumer products were detected at
      elevated levels in the occupied areas. Our results revealed that isoprene and
      many exogenous volatile organic compounds consumed by humans are emitted at
      levels sufficient for detection in the air, which may be indicative of human
      presence. 

PMID- 25944352
TI  - Heterophyid trematodes recovered from people residing along the Boseong River,
      South Korea.
AB  - We conducted an epidemiological survey to determine the status of heterophyid
      fluke infections among people residing along the Boseong River, Gokseong-gun,
      South Korea (= Korea) from October 2011 to February 2012. Fecal specimens were
      collected from 115 (male 51, female 64) people and examined for intestinal
      helminth eggs using the Kato-Katz thick smear technique. The eggs of Metagonimus
      yokogawai together with other Metagonimus spp. were detected in 28 (24.3%) cases.
      Eleven egg positive people were treated with 10mg/kg praziquantel followed by
      MgSO4 purging in order to recover the adult flukes. Whole consecutive diarrheic
      stools were collected individually 4-5 times. Adult flukes recovered were 66,499
      specimens (6045.4/positive case) of M. yokogawai, 343 (38.1) of Metagonimus
      miyatai, 3293 (299.4) of Metagonimus takahashii, 81 (20.3) of Heterophyes nocens,
      6 (3.0) of Heterophyopsis continua, and 1 (1.0) of Stictodora fuscata. The
      results indicated that the surveyed area is a highly endemic area of
      metagonimiasis (three Metagonimus species) with low-grade mixed infections of 3
      other heterophyid flukes. The infected people experienced variable degrees of
      gastrointestinal discomfort and indigestion. They consumed raw freshwater and
      brackish water fish, including sweetfish and mullets. It is strongly recommended
      that people residing in the survey area avoid eating raw fish to prevent M.
      yokogawai and other heterophyid infections. 

PMID- 25944353
TI  - Involvement of metabolic resistance and F1534C kdr mutation in the pyrethroid
      resistance mechanisms of Aedes aegypti in India.
AB  - Pesticide resistance poses a serious problem for worldwide mosquito control
      programs. Resistance to insecticides can be caused by an increased metabolic
      detoxification of the insecticide and/or by target site insensitivity. In the
      present study, we estimated the tolerance of Indian Aedes aegypti populations
      using adult bioassays that revealed high resistance levels of the field
      populations to permethrin (RR-6, 5.8 and 5.1 folds) compared to our susceptible
      population. Enzymatic assays revealed increased activities of glutathione S
      transferase and carboxylesterase enzymes in the field populations comparatively
      to the susceptible population. PBO synergist assays did not confirm that
      cytochrome P450 monooxygenase metabolic detoxification acted as a major cause of
      resistance. Hence the role of target site resistance was therefore investigated.
      A single substitution Phe1534Cys in the voltage gated sodium channel was found in
      domain III, segment 6 (III-S6) of the resistance populations (allele
      frequency=0.59, 0.51 and 0.47) suggesting its potential role in permethrin
      resistance in A. aegypti. 

PMID- 25944351
TI  - Circulating cytokines and chemokines associated with plasma leakage and hepatic
      dysfunction in Brazilian children with dengue fever.
AB  - Dengue fever is usually a benign acute viral infection transmitted by arthropods
      but may evolve to severe clinical manifestations such as coagulation and/or
      hemodynamic disorders, caused mainly by an increase of vascular permeability.
      Deregulated circulating immunological factors have been associated with severity.
      In Brazil severe cases appeared in children only recently and we evaluated the
      profile of cytokine/chemokine kinetics in 134 hospitalized young patients during
      the epidemic in Rio de Janeiro in 2008. Inflammatory cytokines TNF and IFNgamma
      were found elevated during the acute phase in children as well as the anti
      inflammatory IL10 and chemokines MIF and CXCL10/IP10, all last three persisting
      longer during the recovery phase. Severe disease fitting the dengue hemorrhagic
      fever pattern (WHO, 1997) was associated with higher IL10 and CXCL10/IP10
      circulating levels (peak levels at seven days with P<0.01 and P<0.001
      respectively as compared to DF). These factors were higher in patients pulmonary
      effusion or ascites (P<0.05 for IL10 and P<0.01 for CXCL10/IP10). Both factors
      were also associated with liver changes such as AST increase correlated with
      CXCL10/IP10 (r=0.4300 with P<0.0001) and patients presenting painful hepatomegaly
      showed higher circulating levels of IL10 (P<0.01, at 7-9 days) and of CXCL10/IP10
      (P<0.05, 4-6 days and P<0.001, 7-9 days) when compared to patients without
      apparent liver alterations. Most cases presented a history of prior infection
      (93%). This is the first study demonstrating cytokine and chemokine association
      with severity during dengue fever in Brazilian children. IL10 and CXCL10/IP10
      play a role in the disease severity associated with induction of vascular leakage
      and a novel association with changes in liver dysfunction. 

PMID- 25944354
TI  - Host interactions of Chandipura virus matrix protein.
AB  - The rhabdovirus matrix (M) protein is a multifunctional virion protein that plays
      major role in virus assembly and budding, virus-induced inhibition of host gene
      expression and cytopathic effects observed in infected cells. The myriad roles
      played by this protein in the virus biology make it a critical player in viral
      pathogenesis. Therefore, discerning the interactions of this protein with host
      can greatly facilitate our understanding of virus infections, ultimately leading
      to both improved therapeutics and insight into cellular processes. Chandipura
      virus (CHPV; Family Rhabdoviridae, Genus Vesiculovirus) is an emerging
      rhabdovirus responsible for several outbreaks of fatal encephalitis among
      children in India. The present study aims to screen the human fetal brain cDNA
      library for interactors of CHPV M protein using yeast two-hybrid system. Ten host
      protein interactors were identified, three of which were further validated by
      affinity pull down and protein interaction ELISA. The study identified novel
      human host interactors for CHPV which concurred with previously described
      associations in other human viruses. 

PMID- 25944355
TI  - How are you? Do people with inflammatory bowel disease experience response shift
      on this question?
AB  - BACKGROUND: As individuals experience changes in their health, they may alter the
      way they evaluate health and quality of life. The purpose of this study is to
      estimate the extent to which individuals with IBD change their rating of health
      over time because of response shift (RS). METHODS: This is a reanalysis of a
      population-based longitudinal study of IBD in Manitoba, Canada (n = 388). RS was
      examined using trajectories of the difference between observed and predicted
      health. Logistic regression and dual trajectories were used to identify
      predictors of RS. RESULTS: Disease activity, vitality, pain, somatization, and
      physical and social function explained 51% of the variation in general health
      over two years with no evidence of RS in 82% of the sample. Negative RS was found
      for 8%, who initially rated health better than predicted; positive RS was found
      for 6%. The positive RS group was younger and had better baseline scores on
      measures of general health, hostility, pain, mental health and social and role
      function; less pain and better social function scores at baseline were predictors
      of negative RS. CONCLUSIONS: In conclusion, the majority of people with IBD did
      not demonstrate a RS indicating that the health rating over time was stable in
      relation to that predicted by known time varying clinical variables. This adds to
      the evidence that the single question on self-rated health is useful for
      monitoring individuals over time.

PMID- 25944356
TI  - Quantitative evaluation of apically extruded debris with Twisted File Adaptive
      instruments in straight root canals: reciprocation with different angles,
      adaptive motion and continuous rotation.
AB  - AIM: To evaluate the influence of movement kinematics when using Twisted File
      Adaptive instruments (SybronEndo, Orange, CA, USA) (TF Adaptive) on the amount of
      apically extruded debris. METHODOLOGY: Forty-eight extracted mandibular incisor
      teeth were selected. The teeth were randomly divided into four groups (n ? 12),
      and the root canals were instrumented using the following movement kinematics: TF
      Adaptive motion, 90 degrees  clockwise (CW) to 30 degrees  counterclockwise (CCW)
      reciprocating motion, 150 degrees CW to 30 degrees CCW reciprocating motion or
      continuous rotation. TF Adaptive instruments were used for all groups. Debris
      extruded apically during instrumentation was collected in pre-weighed Eppendorf
      tubes, and after drying, the mean weight of the debris was assessed with an
      electronic balance. The data were analysed statistically using a one-way analysis
      of variance. RESULTS: The 90 degrees  CW to 30 degrees  CCW reciprocating motion
      produced the highest mean extrusion value, and this was significantly greater
      when compared with continuous rotation (P < 0.05). 150 degrees  CW to 30 degrees 
      CCW reciprocating, adaptive and continuous rotation motions produced similar
      amounts of debris extrusion (P > 0.05). CONCLUSION: Movement kinematics affected
      the amount of apically extruded debris when using Twisted File Adaptive
      instruments.

PMID- 25944358
TI  - Using Dielectric Relaxation Spectroscopy to Characterize the Glass Transition
      Time of Polydextrose.
AB  - Dielectric relaxation spectroscopy was used to characterize the glass transition
      time, tg , of polydextrose, where the glass transition temperature, Tg , and
      water activity, aw (relative humidity), were held constant during polydextrose
      relaxation. The tg was determined from a shift in the peak frequency of the
      imaginary capacitance spectrum with time. It was found that when the peak
      frequency reaches 30 mHz, polydextrose undergoes glass transition. Glass
      transition time, tg , is the time for polydextrose to undergo glass transition at
      a specific Tg and aw . Results lead to a modified state diagram, where Tg is
      depressed with increasing aw . This curve forms a boundary: (a) below the
      boundary, polydextrose does not undergo glass transition and (b) above the
      boundary, polydextrose rapidly undergoes glass transition. As the boundary curve
      is specified by a tg value, it can assist in the selection of storage conditions.
      An important point on the boundary curve is at aw = 0, where Tg0 = 115  degrees
      C. The methodology can also be used to calculate the stress-relaxation viscosity
      of polydextrose as a function of Tg and aw , which is important when
      characterizing the flow properties of polydextrose initially in powder form. 

PMID- 25944357
TI  - Nuclear roles for actin.
AB  - Actin's presence in the nucleus is a subject that has ignited a lot of
      controversy in the past. With our review, we attempt to reach out not only to the
      specialists but also to a broader audience that might be skeptical in light of
      the controversies. We take a rather conservative approach to build an argument
      that recent studies provide multiple independent lines of evidence substantiating
      actin's diverse nuclear functions, especially in its monomeric state. We then
      particularly focus on how the concentration of monomeric actin, and potentially
      of specific polymerized forms of actin, can be used by the cell as indicators of
      cellular state and how this information can be transduced into the nucleus by
      transcriptional regulators, eliciting a response. We also provide examples that
      in specific cell types and specific physiological conditions, actin is functional
      in the nucleus in its polymeric form. However, we also discuss that in many
      instances, the presence of actin regulators in the nucleus, which is often seen
      as proof of their function within this compartment, may simply reflect an
      additional means of their regulation by compartmentalization. 

PMID- 25944359
TI  - Quantitative Proteomics Analysis of Camelina sativa Seeds Overexpressing the AGG3
      Gene to Identify the Proteomic Basis of Increased Yield and Stress Tolerance.
AB  - Camelina sativa, a close relative of Arabidopsis, is an oilseed plant that is
      emerging as an important biofuel resource. The genome and transcriptome maps of
      Camelina have become available recently, but its proteome composition remained
      unexplored. A labeling LC-based quantitative proteomics approach was applied to
      decipher the Camelina seed proteome, which led to the identification of 1532
      proteins. In addition, the effect of overexpression of the Arabidopsis G-protein
      gamma subunit 3 (AGG3) on the Camelina seed proteome was elucidated to identify
      the proteomic basis of its increased seed size and improved stress tolerance. The
      comparative analysis showed a significantly higher expression of proteins
      involved in primary and secondary metabolism, nucleic acid and protein
      metabolism, and abscisic acid related responses, corroborating the physiological
      effects of AGG3 overexpression. More importantly, the proteomic data suggested
      involvement of the AGG3 protein in the regulation of oxidative stress and heavy
      metal stress tolerance. These observations were confirmed by the physiological
      and biochemical characterization of AGG3-overexpressing seeds, which exhibit a
      higher tolerance to exogenous cadmium in a glutathione-dependent manner. The
      activity of multiple redox-regulating enzymes is higher in seeds expressing
      enhanced levels of AGG3. Overall, these data provide critical evidence for the
      role of redox regulation by the AGG3 protein in mediating important seed-related
      traits. 

PMID- 25944360
TI  - Rabies Post-Exposure Prophylaxis is not Indicated Following Fox-Related Injuries
      Occurring in France.

PMID- 25944361
TI  - Evolution of water sorption in catalyst coated membranes subjected to combined
      chemical and mechanical degradation.
AB  - Catalyst coated perfluorosulfonic acid ionomer membranes (CCMs) were subjected to
      a combined chemical/mechanical accelerated stress test (AST) designed for rapid
      benchmarking of in situ membrane stability in polymer electrolyte fuel cells. In
      order to understand the evolution of the ionomer water sorption characteristics
      during combined chemical/mechanical degradation, CCM samples were periodically
      extracted from the AST and analyzed for ionomer mass fraction and water sorption
      properties. In spite of severe fluoride release and membrane thinning, the water
      uptake per unit mass of the partially degraded CCMs was found to be essentially
      constant. The mass fraction of ionomer in the CCM samples determined from
      thermogravimetric analysis (TGA) showed significant material loss throughout the
      AST process due to ionomer degradation and fluoride release, up to roughly 50% at
      end-of-life. The effects proceeding at different stages of degradation were
      therefore more accurately revealed by ionomer mass-normalized data. The water
      uptake per unit gram of ionomer was shown to increase significantly with
      degradation, in contrast to the previous results normalized by CCM dry mass.
      Although increased water sorption may indicate enlarged solvated hydrophilic
      domains in the membrane, which would be beneficial for enhanced proton mobility,
      the proton conductivity was found to decrease. This finding suggests that the
      additional water sorbed in the membrane was not contributing to proton conduction
      and was therefore likely situated in non-ionic cavities formed through
      degradation rather than in the ionic clusters. 

PMID- 25944366
TI  - Transformation of [M + 2H](2+) Peptide Cations to [M - H](+), [M + H + O](+), and
      M(+*) Cations via Ion/Ion Reactions: Reagent Anions Derived from Persulfate.
AB  - The gas-phase oxidation of doubly protonated peptides is demonstrated here using
      ion/ion reactions with a suite of reagents derived from persulfate. Intact
      persulfate anion (HS2O8(-)), peroxymonosulfate anion (HSO5(-)), and sulfate
      radical anion (SO4(-*)) are all either observed directly upon negative
      nanoelectrospray ionization (nESI) or easily obtained via beam-type collisional
      activation of persulfate into the mass spectrometer. Ion/ion reactions between
      each of these reagents and doubly protonated peptides result in the formation of
      a long-lived complex. Collisional activation of the complex containing a
      peroxymonosulfate anion results in oxygen transfer from the reagent to the
      peptide to generate the [M + H + O](+) species. Activation of the complex
      containing intact persulfate anion either results in oxygen transfer to generate
      the [M + H + O](+) species or abstraction of two hydrogen atoms and a proton to
      generate the [M - H](+) species. Activation of the complex containing sulfate
      radical anion results in abstraction of one hydrogen atom and a proton to form
      the peptide radical cation, [M](+*). This suite of reagents allows for the facile
      transformation of the multiply protonated peptides obtained via nESI into a
      variety of oxidized species capable of providing complementary information about
      the sequence and structure of the peptide.

PMID- 25944367
TI  - Mass Spectrometry of Nanoparticles is Different.
AB  - Secondary ion mass spectrometry, SIMS, is a method of choice for the
      characterization of nanoparticles, NPs. For NPs with large surface-to-volume
      ratios, heterogeneity is a concern. Assays should thus be on individual nano
      objects rather than an ensemble of NPs; however, this may be difficult or
      impossible. This limitation can be side-stepped by probing a large number of
      dispersed NPs one-by-one and recording the emission from each NP separately. A
      large collection of NPs will likely contain subsets of like-NPs. The experimental
      approach is to disperse the NPs and hit an individual NP with a single massive
      cluster (e.g., C-60, Au-400). At impact energies of ~1 keV/atom, they generate
      notable secondary ion (SI) emission. Examination of small NPs (<=20 nm in
      diameter) shows that the SI emission is size-dependent and impacts are not all
      equivalent. Accurate identification of the type of impact is key for qualitative
      assays of core or outer shell composition. For quantitative assays, the concept
      of effective impacts is introduced. Selection of co-emitted ejecta combined with
      rejection (anticoincidence) of substrate ions allows refining chemical
      information within the projectile interaction volume. Last, to maximize the SI
      signal, small NPs (<=5 nm in diameter) can be examined in the transmission mode
      where the SI yields are enhanced ~10-fold over those in the (conventional)
      reflection direction. Future endeavors should focus on schemes acquiring SIs,
      electrons, and photons concurrently.

PMID- 25944368
TI  - Evaluation of Mindray BC-5000 hematology analyzer: a new miniature 5-part WBC
      differential instrument.
AB  - INTRODUCTION: The Mindray BC-5000 automated hematology analyzer is a miniature,
      automated hematology analyzer, and 5-part leukocyte differential counter for in
      vitro diagnostic use in clinical laboratories. METHODS: Precision, linearity,
      carryover, and method comparison were carried out. The analyzer was evaluated and
      compared with the Sysmex XE-2100 hematology analyzer and manual microscopic in
      the hematology laboratory of a tertiary hospital in Chinese. RESULTS: There were
      minimal carryover (<0.25%), and excellent linearity for white blood cell, and
      platelet counts (r > 0.99). Within-run precision was good at all levels for the
      routine cell blood count parameters (CV < 3.5%). Between-run precision was
      acceptable at all levels for the analysis parameters (CV < 5%) except for
      eosinophil and basophil (CV% >10%). BC-5000 displayed very good correlation (r >
      0.94) with the XE-2100 for cell blood count and cell differential parameters
      except for basophil (r = 0.72). The comparison of 258 leukocyte differential
      count results analyzed in parallel with manual microscopy, BC-5000 analyzer
      showed perfect specificity (93%) and negative predictive value (90%) on abnormal
      blood samples. CONCLUSION: It is concluded that the overall performance of the BC
      5000 is acceptable. The miniature analyzer is suitable for use in small- to
      medium-size laboratories.

PMID- 25944369
TI  - Cationic dendronization of amylose via click chemistry for complexation and
      transfection of plasmid DNA.
AB  - For the development of effective and safe gene carrier based on starch, the
      amylose from potato starch was azidized by reacting with 3-azidopropylamine in
      the presence of N, N'-carbonyldiimidazole and then conjugated with propargyl
      focal point poly(amidoamine) (PAMAM) dendrons by a Cu(I)-catalyzed azide-alkyne
      cycloaddition. Such a cationic dendronization was verified by Fourier transform
      infrared spectroscopy and proton nuclear magnetic resonance analyses. For the
      resultant amylose conjugates with various contents and generations of PAMAM
      dendron, their buffering capacity, binding ability with plasmid DNA and in vitro
      cytotoxicity were investigated. These amylose conjugates were found to exhibit
      good buffering capacity and biocompatibility. In particular, they could condense
      effectively plasmid DNA into the nanocomplexes, as confirmed by agarose gel
      electrophoresis, zeta potential, and particle size analyses as well as
      transmission electron microscopy observation. For their nanocomplexes with
      plasmid DNA, the in vitro transfection properties in human embryonic kidney 293T
      cells were studied by fluorescence microscopy and flow cytometry. It was found
      that the transfection efficiency could be optimized by the dendronization extent
      of amylose and the complexation extent of dendronized amylose with plasmid DNA. 

PMID- 25944370
TI  - Characterization of pH-induced transitions of Entamoeba histolytica D
      phosphoglycerate dehydrogenase.
AB  - Entamoeba histolytica D-phosphoglycerate dehydrogenase (EhPGDH) exists as a
      functionally active homodimer at pH 7. Our earlier studies have shown that ionic
      interactions are essentially required for the oligomeric status and activity of
      the protein. Present study focuses on pH associated structural modulations of
      EhPGDH. Far-UV CD spectra showed loss in the secondary structure of the protein
      as a function of low pH, however, the protein was not completely unfolded even at
      pH 2. Energy minimized average simulated models of EhPGDH at different pH show
      stable secondary structure elements in the nucleotide binding domain (NBD)
      however, the substrate binding domain (SBD) was more sensitive toward acidic pH
      and completely unfolds at pH 2. The data suggest presence of partially
      folded/unfolded intermediate state at pH 2. Size exclusion chromatography shows
      that this intermediate has larger hydrodynamic radius compared with dimer (pH 7)
      or monomer (pH 5). The intermediate has poor tertiary organization with
      significantly exposed hydrophobic patches monitored by pH-dependent fluorescence
      spectroscopy and molecular dynamic simulations. Collectively, the results suggest
      that the two domains (NBD and SBD) of EhPGDH have independent pH-dependent
      structural transitions with stabilization of an intermediate state at pH 2.

PMID- 25944372
TI  - Variations on the Village Model.
AB  - Villages, which are community-based initiatives designed to help older adults age
      in place through a combination of services, participant engagement, and peer
      support, have expanded rapidly since their initial development in the early
      2000s. Using a sample of Villages in the United States, we examined variations
      from characteristics of the Village model as portrayed by media and
      organizational leaders. Results indicate there is no uniform Village model that
      can be implemented and evaluated by policy makers, funders, service providers,
      and researchers. Based on the extent of member involvement, methods of service
      provision, and funding sources, we developed a conceptually and empirically
      informed typology of Villages that reflects the model's focus on consumer
      involvement. Descriptive analyses indicate potential differences in member,
      community, and organizational characteristics. This emerging typology has
      implications for understanding the implementation and sustainability of Villages,
      including whether specific Village types are best suited to certain community
      contexts.

PMID- 25944371
TI  - Prospective associations and population impact of sweet beverage intake and type
      2 diabetes, and effects of substitutions with alternative beverages.
AB  - AIMS/HYPOTHESIS: This study aimed to evaluate the association of types of sugar
      sweetened beverages (SSB) (soft drinks, sweetened-milk beverages, sweetened
      tea/coffee), artificially sweetened beverages (ASB) and fruit juice with incident
      type 2 diabetes and determine the effects of substituting non-SSB for SSB and the
      population-attributable fraction of type 2 diabetes due to total sweet beverages.
      METHODS: Beverage consumption of 25,639 UK-resident adults without diabetes at
      baseline (1993-1997) in the European Prospective Investigation into Cancer and
      Nutrition (EPIC)-Norfolk study was assessed using 7-day food diaries. During 10.8
      years of follow-up 847 incident type 2 diabetes cases were verified. RESULTS: In
      adjusted Cox regression analyses there were positive associations (HR [95% CI]
      per serving/day]) for soft drinks 1.21 (1.05, 1.39), sweetened-milk beverages
      1.22 (1.05, 1.43) and ASB 1.22 (1.11, 1.33), but not for sweetened tea/coffee
      0.98 (0.94, 1.02) or fruit juice 1.01 (0.88, 1.15). Further adjustment for
      adiposity attenuated the association of ASB, HR 1.06 (0.93, 1.20). There was a
      positive dose-response relationship with total sweet beverages: HR per 5% energy
      1.18 (1.11, 1.26). Substituting ASB for any SSB did not reduce the incidence in
      analyses accounting for energy intake and adiposity. Substituting one serving/day
      of water or unsweetened tea/coffee for soft drinks and for sweetened-milk
      beverages reduced the incidence by 14%-25%. If sweet beverage consumers reduced
      intake to below 2% energy, 15% of incident diabetes might be prevented.
      CONCLUSIONS/INTERPRETATION: The consumption of soft drinks, sweetened-milk
      beverages and energy from total sweet beverages was associated with higher type 2
      diabetes risk independently of adiposity. Water or unsweetened tea/coffee appear
      to be suitable alternatives to SSB for diabetes prevention. These findings
      support the implementation of population-based interventions to reduce SSB
      consumption and increase the consumption of suitable alternatives.

PMID- 25944373
TI  - Ursane-type nortriterpenes with a five-membered A-ring from Rubus innominatus.
AB  - Two nortriterpenes (rubuminatus A and B), which contain a distinctive contracted
      a five-membered A-ring ursane-type skeleton, and six triterpenes along with 17
      known triterpenes were isolated from the roots of Rubus innominatus S. Moore.
      These structures were determined to be 19alpha-hydroxy-2-oxo-nor- A(3)-urs-12-en
      28-oic acid, 1beta,19alpha-dihydroxy-2-oxo-nor-A(3)-urs-12-en-28-oic acid,
      1beta,2alpha,3alpha,19alpha-tetrahy droxyurs-12-en-23-formyl-28-oic acid,
      1beta,2alpha,3alpha,19alpha,23- pentahydroxyurs-11-en-28-oic acid, 1-oxo
      siaresinolic acid, 2alpha,3alpha-dihydroxyolean-11,13(18)-dien-19beta,28-olide,
      1beta,2alpha,3alpha-trihydroxy-19-oxo- 18,19-seco-urs-11,13(18)-dien-28-oic acid,
      and 2-O-benzoyl alphitolic acid based on extensive spectroscopic analyses. In
      vitro anti-inflammatory abilities to modulate the production of TNF-alpha, IL
      1beta, and IL-6 in LPS-induced RAW 264.7 macrophages of the compounds were
      determined. Rubuminatus A and B, as well as 1-oxo-siaresinolic acid and
      2alpha,3alpha-dihydroxyolean-11,13(18)-dien-19beta,28-olide, exhibited
      significant inhibitory effects on these cytokines. 

PMID- 25944375
TI  - Response to Phelan K. et al.: letter to the editor regarding Disciglio et al:
      interstitial 22q13 deletions not involving SHANK3 gene: a new contiguous gene
      syndrome.

PMID- 25944374
TI  - Small peptides hydrolysis in dry-cured meats.
AB  - Large amounts of different peptides are naturally generated in dry-cured meats as
      a consequence of the intense proteolysis mechanisms which take place during their
      processing. In fact, meat proteins are extensively hydrolysed by muscle endo
      peptidases (mainly calpains and cathepsins) followed by exo-peptidases (mainly,
      tri- and di-peptidyl peptidases, dipeptidases, aminopeptidases and
      carboxypeptidases). The result is a large amount of released free amino acids and
      a pool of numerous peptides with different sequences and lengths, some of them
      with interesting sequences for bioactivity. This manuscript is presenting the
      proteomic identification of small peptides resulting from the hydrolysis of four
      target proteins (glyceraldehyde-3-phosphate dehydrogenase, beta-enolase, myozenin
      1 and troponin T) and discusses the enzymatic routes for their generation during
      the dry-curing process. The results indicate that the hydrolysis of peptides
      follows similar exo-peptidase mechanisms. In the case of dry-fermented sausages,
      most of the observed hydrolysis is the result of the combined action of muscle
      and microbial exo-peptidases except for the hydrolysis of di- and tri-peptides,
      mostly due to microbial di- and tri-peptidases, and the release of amino acids at
      the C-terminal that appears to be mostly due to muscle carboxypeptidases. 

PMID- 25944376
TI  - Long-term results of prednisone treatment for the anemia of myelofibrosis.
AB  - This study has retrospectively analyzed the efficacy of single-agent prednisone,
      usually given after failure of other therapies, in 30 patients with myelofibrosis
      (MF) and severe anemia. Initial dose was 0.5-1 mg/kg daily, with tapering to the
      minimum effective dose in responders. Twelve patients (40%) achieved anemia
      response according to the revised International Working Group for Myelofibrosis
      Research and Treatment criteria, after a median time of 1.1 months on treatment.
      Median response duration was 12.3 months. Patients with constitutional symptoms
      or > 2% circulating blasts had a trend for a lower response rate. A platelet
      increase > 50 * 10(9)/L was observed in three out of 11 patients with baseline
      counts < 100 * 10(9)/L. Median survival from prednisone start was significantly
      longer in anemia responders (5.0 years, 95% CI = 3.5-6.5, vs 1.5 years, 95% CI =
      0.2-2.8; p = 0.002). Prednisone can improve the anemia and thrombocytopenia in
      selected MF patients after failure to standard therapies. 

PMID- 25944377
TI  - Management of venous thromboembolism in patients with acute leukemia at high
      bleeding risk: a multi-center study.
AB  - In the last decades, evaluation of clinically relevant thrombotic complications
      in patients with acute leukemia (AL) has been poorly investigated. The authors
      performed a multi-center study to evaluate the management of symptomatic venous
      thromboembolism (VTE) in adult patients with AL. The intention was to find as
      clinically relevant the following: symptomatic Venous Thrombosis (VT) occurred in
      typical (lower limbs) and atypical (cerebral, upper limbs, abdominal, etc) sites
      with or without pulmonary embolism (PE). Over a population of 1461 patients with
      AL, 22 cases of symptomatic VTE were recorded in hospitalized patients with a
      mean age of 54.6 years. The absolute incidence of VTE was 1.5%. VTE occurred
      during chemotherapy in 17/22 (77.2%) cases, mainly (14/17, 82.3%) during the
      induction phase. Treatment of acute VTE was based on Low Molecular Weight Heparin
      (LMWH) at full dosage for the first month from diagnosis and reduced dosage (75%)
      for the following months. 

PMID- 25944378
TI  - Infections associated with bendamustine containing regimens in hematological
      patients: a retrospective multi-center study.
AB  - A multi-center retrospective analysis of a cohort of patients in Israel treated
      with any bendamustine containing regimen between 2010-2014 was performed in order
      to determine the incidence and predictors for infection. The Kaplan Meier Model,
      employing log rank analysis, was used to assess time-to-infection. The Cox
      Proportional Hazards model was used to analyze multivariate effects of risk and
      234 patients were included in the analysis. One hundred and nine (46.6%)
      developed at least one infection and 33.76% had severe infections. Seventy-six
      (41.5%) developed bacterial infection, nine (3.8%) fungal infection and 26
      (11.5%) had viral infections. Factors significantly associated with time to
      infection on multivariable analysis were: bendamustine-combinations [hazard ratio
      (HR) = 0.589 (95% CI = 0.374-0.926), p = 0.022], Hb level [HR = 0.791 (95% CI =
      0.716-0.875), p < 0.0001] and ischemic heart disease [HR = 1.828 (95% CI = 1.165
      2.868), p = 0.009]. Infections were associated with a higher mortality and
      hospitalization rate. 

PMID- 25944379
TI  - Advances and issues in mantle cell lymphoma research: report of the 2014 Mantle
      Cell Lymphoma Consortium Workshop.
AB  - Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma
      characterized by the t(11;14) chromosomal translocation and cyclin D1 over
      expression. A biologically and clinically heterogeneous lymphoma, MCL, remains
      clinically challenging, with no proven curative therapy and no established
      standard of care. However, there have been considerable advances in the last
      several years in the treatment and understanding of MCL with the FDA approval of
      lenalidomide and ibrutinib, the development of other potentially active novel
      agents and the identification of recurrent mutations through new genomic
      sequencing approaches that may contribute to the biology of MCL and to
      therapeutic resistance. At the Lymphoma Research Foundation's 11th MCL Workshop,
      researchers gathered to discuss recent studies and current issues related to the
      biology of MCL, novel therapeutic targets and new treatment strategies. The
      presentations are summarized in this manuscript, which is intended to highlight
      areas of active investigation and identify topics for future research. 

PMID- 25944380
TI  - Genetic epidemiology, prevalence, and genotype-phenotype correlations in the
      Swedish population with osteogenesis imperfecta.
AB  - Osteogenesis imperfecta (OI) is a rare hereditary bone fragility disorder, caused
      by collagen I mutations in 90% of cases. There are no comprehensive genotype
      phenotype studies on >100 families outside North America, and no population-based
      studies determining the genetic epidemiology of OI. Here, detailed clinical
      phenotypes were recorded, and the COL1A1 and COL1A2 genes were analyzed in 164
      Swedish OI families (223 individuals). Averages for bone mineral density (BMD),
      height and yearly fracture rate were calculated and related to OI and mutation
      type. N-terminal helical mutations in both the alpha1- and alpha2-chains were
      associated with the absence of dentinogenesis imperfecta (P<0.0001 vs 0.0049),
      while only those in the alpha1-chain were associated with blue sclera (P=0.0110).
      Comparing glycine with serine substitutions, alpha1-alterations were associated
      with more severe phenotype (P=0.0031). Individuals with type I OI caused by
      qualitative vs quantitative mutations were shorter (P<0.0001), but did not differ
      considering fractures or BMD. The children in this cohort were estimated to
      represent >95% of the complete Swedish pediatric OI population. The prevalence of
      OI types I, III, and IV was 5.16, 0.89, and 1.35/100 000, respectively (7.40/100
      000 overall), corresponding to what has been estimated but not unequivocally
      proven in any population. Collagen I mutation analysis was performed in the
      family of 97% of known cases, with causative mutations found in 87%. Qualitative
      mutations caused 32% of OI type I. The data reported here may be helpful to
      predict phenotype, and describes for the first time the genetic epidemiology in
      >95% of an entire OI population.

PMID- 25944381
TI  - DYRK1A haploinsufficiency causes a new recognizable syndrome with microcephaly,
      intellectual disability, speech impairment, and distinct facies.
AB  - Dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A ) is a
      highly conserved gene located in the Down syndrome critical region. It has an
      important role in early development and regulation of neuronal proliferation.
      Microdeletions of chromosome 21q22.12q22.3 that include DYRK1A (21q22.13) are
      rare and only a few pathogenic single-nucleotide variants (SNVs) in the DYRK1A
      gene have been described, so as of yet, the landscape of DYRK1A disruptions and
      their associated phenotype has not been fully explored. We have identified 14
      individuals with de novo heterozygous variants of DYRK1A; five with
      microdeletions, three with small insertions or deletions (INDELs) and six with
      deleterious SNVs. The analysis of our cohort and comparison with published cases
      reveals that phenotypes are consistent among individuals with the 21q22.12q22.3
      microdeletion and those with translocation, SNVs, or INDELs within DYRK1A. All
      individuals shared congenital microcephaly at birth, intellectual disability,
      developmental delay, severe speech impairment, short stature, and distinct facial
      features. The severity of the microcephaly varied from -2 SD to -5 SD. Seizures,
      structural brain abnormalities, eye defects, ataxia/broad-based gait,
      intrauterine growth restriction, minor skeletal abnormalities, and feeding
      difficulties were present in two-thirds of all affected individuals. Our study
      demonstrates that haploinsufficiency of DYRK1A results in a new recognizable
      syndrome, which should be considered in individuals with Angelman syndrome-like
      features and distinct facial features. Our report represents the largest cohort
      of individuals with DYRK1A disruptions to date, and is the first attempt to
      define consistent genotype-phenotype correlations among subjects with 21q22.13
      microdeletions and DYRK1A SNVs or small INDELs. 

PMID- 25944382
TI  - Chromosome 22q12.1 microdeletions: confirmation of the MN1 gene as a candidate
      gene for cleft palate.
AB  - We report on seven novel patients with a submicroscopic 22q12 deletion. The
      common phenotype constitutes a contiguous gene deletion syndrome on chromosome
      22q12.1q12.2, featuring NF2-related schwannoma of the vestibular nerve, corpus
      callosum agenesis and palatal defects. Combining our results with the literature,
      eight patients are recorded with palatal defects in association with
      haploinsufficiency of 22q12.1, including the MN1 gene. These observations,
      together with the mouse expression data and the finding of craniofacial
      malformations including cleft palate in a Mn1-knockout mouse model, suggest that
      this gene is a candidate gene for cleft palate in humans. 

PMID- 25944383
TI  - Neurobehavioral impairments caused by developmental imidacloprid exposure in
      zebrafish.
AB  - BACKGROUND: Neonicotinoid insecticides are becoming more widely applied as
      organophosphate (OP) insecticides are decreasing in use. Because of their
      relative specificity to insect nicotinic receptors, they are thought to have
      reduced risk of neurotoxicity in vertebrates. However, there is scant published
      literature concerning the neurobehavioral effects of developmental exposure of
      vertebrates to neonicotinoids. METHODS: Using zebrafish, we investigated the
      neurobehavioral effects of developmental exposure to imidacloprid, a prototypic
      neonicotinoid pesticide. Nicotine was also administered for comparison. Zebrafish
      were exposed via immersion in aqueous solutions containing 45 MUM or 60 MUM of
      imidacloprid or nicotine (or vehicle control) from 4h to 5d post fertilization.
      The functional effects of developmental exposure to both imidacloprid and
      nicotine were assessed in larvae using an activity assay and during adolescence
      and adulthood using a battery of neurobehavioral assays, including assessment of
      sensorimotor response and habituation in a tactile startle test, novel tank
      swimming, and shoaling behavior. RESULTS: In larvae, developmental imidacloprid
      exposure at both doses significantly decreased swimming activity. The 5D strains
      of zebrafish were more sensitive to both nicotine and imidacloprid than the AB*
      strain. In adolescent and adult fish, developmental exposure to imidacloprid
      significantly decreased novel tank exploration and increased sensorimotor
      response to startle stimuli. While nicotine did not affect novel tank swimming,
      it increased sensorimotor response to startle stimuli at the low dose. No effects
      of either compound were found on shoaling behavior or habituation to a startling
      stimulus. DISCUSSION: Early developmental exposure to imidacloprid has both early
      life and persisting effects on neurobehavioral function in zebrafish. Its
      developmental neurotoxicity should be further investigated.

PMID- 25944384
TI  - A Combined Shotgun and Targeted Mass Spectrometry Strategy for Breast Cancer
      Biomarker Discovery.
AB  - It is of highest importance to find proteins responsible for breast cancer
      dissemination, for use as biomarkers or treatment targets. We established and
      performed a combined nontargeted LC-MS/MS and a targeted LC-SRM workflow for
      discovery and validation of protein biomarkers. Eighty breast tumors, stratified
      for estrogen receptor status and development of distant recurrence (DR +/- ),
      were collected. After enrichment of N-glycosylated peptides, label-free LC-MS/MS
      was performed on each individual tumor in triplicate. In total, 1515
      glycopeptides from 778 proteins were identified and used to create a map of the
      breast cancer N-glycosylated proteome. Based on this specific proteome map, we
      constructed a 92-plex targeted label-free LC-SRM panel. These proteins were
      quantified across samples by LC-SRM, resulting in 10 proteins consistently
      differentially regulated between DR+/DR- tumors. Five proteins were further
      validated in a separate cohort as prognostic biomarkers at the gene expression
      level. We also compared the LC-SRM results to clinically reported HER2 status,
      demonstrating its clinical accuracy. In conclusion, we demonstrate a combined
      mass spectrometry strategy, at large scale on clinical samples, leading to the
      identification and validation of five proteins as potential biomarkers for breast
      cancer recurrence. All MS data are available via ProteomeXchange and PASSEL with
      identifiers PXD001685 and PASS00643. 

PMID- 25944385
TI  - Low incidence of radionecrosis in children treated with conventional radiation
      therapy and intrathecal radioimmunotherapy.
AB  - Radionecrosis is a potentially devastating complication of external beam
      radiotherapy (XRT). Intraventricular compartmental radioimmunotherapy (cRIT)
      using (131)I-3F8 or (131)I-8H9 can eradicate malignant cells in the CSF. The
      incidence of radionecrosis using cRIT (131)I based intraventricular
      radioimmunotherapy, when used alone or in combination with conventional
      craniospinal CSI-XRT is unknown. We retrospectively analyzed the incidence of
      radionecrosis in two cohorts of pediatric patients treated with both CSI-XRT and
      cRIT at MSKCC since 2003: patients with metastatic CNS neuroblastoma (NB) and
      medulloblastoma (MB). 94 patients received both CSI-XRT and cRIT, two received
      cRIT alone, median follow up 41.5 months (6.5-124.8 months). Mean CSI-XRT dose
      was 28 Gy (boost to the primary tumor site up to 54 Gy) in the MB cohort, and CSI
      XRT dose 18-21 Gy (boost to 30 Gy for focal parenchymal mass) in the NB cohort.
      For MB patients, 20 % had focal re-irradiation for a second or more subsequent
      relapse, mean repeat-XRT dose was 27.5 Gy; seven patients with NB had additional
      focal XRT. Median CSF cRIT dose was 18.6 Gy in the MB cohort and 32.1 in the NB
      cohort. One asymptomatic patient underwent resection of 0.6-cm hemorrhagic
      periventricular white-matter lesion confirmed to be necrosis and granulation
      tissue, 2.5 years after XRT. The risk of radionecrosis in children treated with
      XRT and cRIT appears minimal (~1 %). No neurologic deficits secondary to
      radionecrosis have been observed in long-term survivors treated with both
      modalities, including patients who underwent re-XRT. Administration of cRIT may
      safely proceed in patients treated with conventional radiotherapy without
      appearing to increase the risk of radionecrosis.

PMID- 25944387
TI  - A Pseudo-Regular Alternating Conjugated Copolymer Using an Asymmetric Monomer: A
      High-Mobility Organic Transistor in Nonchlorinated Solvents.
AB  - Pseudo-regular alternating PDPP-TVS copolymers using an asymmetric monomer
      (thiophene-vinylene-selenophene (TVS)) are synthesized. Unlike regular
      alternating copolymers, these polymers are highly soluble in nonchlorinated
      solvents such as tetra-hydrofuran, toluene, xylene, and tetralin. The organic
      field-effect transistor devices fabricated using these polymers dissolved in
      nonchlorinated solvents exhibit a high hole mobility up to 8.2 cm(2) V(-1) s(-1).

PMID- 25944388
TI  - Synthesis of Porous delta-MnO2 Submicron Tubes as Highly Efficient
      Electrocatalyst for Rechargeable Li-O2 Batteries.
AB  - Lithium-oxygen (Li-O2 ) batteries are receiving intense interest because of their
      high energy density. A new tubular delta-MnO2 material prepared by a simple
      hydrothermal synthesis is an efficient electrocatalyst for Li-O2 batteries. The
      synthesized delta-MnO2 exhibits a unique tubular structure, in which the porous
      walls are composed of highly dispersed ultrathin delta-MnO2 nanosheets. Such a
      unique structure and its intrinsic catalytic activity provide the right
      electrocatalyst characteristics for high-performance Li-O2 batteries. As a
      consequence, suppressed overpotentials-especially the oxygen evolution reaction
      overpotential-superior rate capability, and desirable cycle life are achieved
      with these submicron delta-MnO2 tubes as the electrocatalyst. Remarkably, the
      discharge product Li2 O2 of the Li-O2 battery exhibits a uniform nanosheet-like
      morphology, which indicates the critical role of the delta-MnO2 in the
      electrochemical process, and a mechanism is proposed to analyze the catalysis of
      delta-MnO2 . 

PMID- 25944386
TI  - Novel anti IGFBP2 single chain variable fragment inhibits glioma cell migration
      and invasion.
AB  - Insulin like growth factor binding protein 2 (IGFBP2) is highly up regulated in
      glioblastoma (GBM) tissues and has been one of the prognostic indicators. There
      are compelling evidences suggesting important roles for IGFBP2 in glioma cell
      proliferation, migration and invasion. Extracellular IGFBP2 through its carboxy
      terminal arginine glycine aspartate (RGD) motif can bind to cell surface
      alpha5beta1 integrins and activate pathways downstream to integrin signaling.
      This IGFBP2 activated integrin signaling is known to play a crucial role in
      IGFBP2 mediated invasion of glioma cells. Hence a molecular inhibitor of carboxy
      terminal domain of IGFBP2 which can inhibit IGFBP2-cell surface interaction is of
      great therapeutic importance. In an attempt to develop molecular inhibitors of
      IGFBP2, we screened single chain variable fragment (scFv) phage display
      libraries, Tomlinson I (Library size 1.47 * 10(8)) and Tomlinson J (Library size
      1.37 * 10(8)) using human recombinant IGFBP2. After screening we obtained three
      IGFBP2 specific binders out of which one scFv B7J showed better binding to IGFBP2
      at its carboxy terminal domain, blocked IGFBP2-cell surface association, reduced
      activity of matrix metalloprotease 2 in the conditioned medium of glioma cells
      and inhibited IGFBP2 induced migration and invasion of glioma cells. We
      demonstrate for the first time that in vitro inhibition of extracellular IGFBP2
      activity by using human scFv results in significant reduction of glioma cell
      migration and invasion. Therefore, the inhibition of IGFBP2 can serve as a
      potential therapeutic strategy in the management of GBM.

PMID- 25944390
TI  - The Value of Cytokeratin 5/6, p63 and Thyroid Transcription Factor-1 in
      Adenocarcinoma, Squamous Cell Carcinoma and Non-Small-Cell Lung Cancer of the
      Lung.
AB  - OBJECTIVE: It is now important to distinguish between adenocarcinoma and squamous
      cell carcinoma of the lung because of target-specific treatments. Our study aimed
      to study the efficiency of Thyroid Transcription Factor-1 (TTF-1), cytokeratin
      5/6 (CK5/6) and p63 in distinguishing between adenocarcinoma and squamous cell
      carcinoma and to study the contribution of these markers to the diagnosis in non
      small cell lung cancer. MATERIAL AND METHOD: Immunohistochemically, TTF-1, CK 5/6
      and p63 were used in 72 cases of squamous cell carcinoma, 19 cases of
      adenocarcinoma, and 29 cases of non-small cell lung cancer whose final diagnosis
      was decided with the subsequent resection material. The specificity, sensitivity,
      and positive and negative predictive value were calculated for each marker.
      RESULTS: TTF-1 positivity was seen in none of the 72 squamous cell carcinomas but
      in all of 19 adenocarcinoma cases. CK5/6 negativity was seen in all cases of
      adenocarcinoma and in two cases of squamous cell carcinoma. p63 was positive in
      all squamous cell carcinomas and in 4 adenocarcinomas. Cytokeratin 5/6, p63
      positivity and TTF-1 negativity were observed in 17 non-small cell lung cancers
      whose final diagnosis was squamous cell carcinoma. None of the 12 non-small cell
      lung cancers whose final diagnosis was adenocarcinoma exhibited positive staining
      for CK5/6. However, p63 staining was not seen in the biopsy but was focal in the
      surgical specimen in one case. All the 12 non-small cell lung cancers whose
      certain diagnosis was adenocarcinoma were positive for TTF-1. TTF-1, CK 5/6 and
      p63 seem to be useful for differentiating adenocarcinoma from squamous cell
      carcinoma with 100% specificity, 100% sensitivity and 100% specificity, 97%
      sensitivity and 87% specificity, and 100% sensitivity, respectively. CONCLUSION:
      We concluded that TTF-1 is a reliable marker for subtyping lung cancer. Different
      staining patterns can be seen with CK5/6 and p63; however, if they are used
      together with TTF-1 and interpreted correctly, they can be of help for the final
      diagnosis even in cases in which the morphology is unclear.

PMID- 25944389
TI  - Deleterious versus protective autoimmunity in multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disorder
      of central nervous system, in which myelin specific CD4(+) T cells have a central
      role in orchestrating pathological events involved in disease pathogenesis. There
      is compelling evidence that Th1, Th9 and Th17 cells, separately or in
      cooperation, could mediate deleterious autoimmune response in MS. However, the
      phenotype differences between Th cell subpopulations initially employed in MS
      pathogenesis are mainly reflected in the different patterns of inflammation
      introduction, which results in the development of characteristic pathological
      features (blood-brain barrier disruption, demyelination and neurodegeneration),
      clinically presented with MS symptoms. Although, autoimmunity was traditionally
      seen as deleterious, some studies indicated that autoimmunity mediated by Th2
      cells and T regulatory cells could be protective by nature. The concept of
      protective autoimmunity in MS pathogenesis is still poorly understood, but could
      be of great importance in better understanding of MS immunology and therefore,
      creating better therapeutic strategies. 

PMID- 25944391
TI  - Chromosome abnormalities identified in 457 spontaneous abortions and their
      histopathological findings.
AB  - OBJECTIVE: About 15% of clinically recognized pregnancies result in spontaneous
      abortion in the first trimester and the vast majority of these are the result of
      chromosome abnormalities. Studies of chromosomal constitutions of first trimester
      spontaneous abortions have revealed that at least 50% of the abortions have an
      abnormal karyotype. In this study we aimed to report the single centre experience
      of anomalies detected in spontaneous abortions. MATERIAL AND METHOD: We present
      rare numerical and structural cytogenetic abnormalities detected in spontaneous
      abortion materials and the histopathological findings of rest material of
      abortion specimens in our study population. RESULTS: Among 457 cases, 382 were
      successfully karyotyped while cell culture of 75 cases failed. Cytogenetic
      abnormalities were detected in 127 of 382 cases (33.24%). Autosomal trisomies
      were the predominant chromosomal abnormalities with a frequency of 48.8%.
      Structural chromosomal abnormalities were infrequent in conception materials. The
      mean age of the mothers was highest in trisomy group, the difference being
      significantly important (ANOVA p < 0.001). The most frequent chromosomal
      abnormalities were Turner syndrome, triploidy and trisomy of chromosome 16
      followed by trisomy of chromosomes 22 and 21 and tetraploidy. Double trisomies
      and structural chromosomal abnormalities were rare. Trisomies were more frequent
      in advanced maternal age. CONCLUSION: Detection of chromosomal abnormalities in
      spontaneous abortion materials is very important to clarify the causes of loss of
      pregnancy. Detection of structural chromosomal abnormalities in the cases and
      their carrier parents can provide proper genetic counseling to these families.
      These families can be directed towards pre-implantation genetic diagnosis to
      prevent further pregnancies with complications.

PMID- 25944392
TI  - Clinicopathological evaluation of cutaneous leishmaniasis in the mediterranean
      region of Turkey.
AB  - OBJECTIVE: Cutaneus leishmaniasis, a chronic self-limited disease of the skin, is
      usually caused by Leishmania Tropica. It is endemic in Southeastern Anatolia. The
      definitive diagnosis depends on demonstration of the parasites by smear and
      culture or its identification in tissue section. This study aimed to evaluate
      clinical and histopathological skin lesions in cutaneous leishmaniasis cases in
      Antalya, Turkey. MATERIAL AND METHOD: Our study included 28 patients diagnosed
      with cutaneous leishmaniasis at the Pathology Department of Akdeniz University
      Medical Faculty. Histopathological sections were stained with Haematoxylin-Eosin,
      Giemsa or Leishman for visual examination of cellular components by two
      dermatopathologists. The epidermal (acanthosis, hyper-parakeratosis, atrophy,
      lymphocytic exocytosis) and dermal changes that may indicate lymphohistiocytic
      infiltration and granuloma formation were investigated. The parasitic load was
      classified according to the modified Ridley's parasitic index. RESULTS: Out of 28
      cases, 11 had hyperparakeratosis, 17 had orthokeratosis, 20 had acanthosis, 4 had
      epidermal atrophy, and 7 had exocytosis. Typical epithelioid cell granulomas with
      giant cells and a rim of lymphocytes were present in 16 cases. Leishman-Donovan
      bodies were extremely rare in typical granulomatous lesions. The other 12 cases
      showed lymphohistiositic infiltration, giant cells and prominent plasma cells.
      There were numerous Leishman-Donovan bodies in these lesions. CONCLUSION: We
      investigated the epidermal and dermal changes that would facilitate the
      histopathological diagnosis of cutaneous leishmaniasis in this study. We found
      that atrophy, acanthosis, and orthokeratosis were early stage indicators, while
      exocytosis, hyperparakeratosis, and atrophy were indicative of late stage
      disease.

PMID- 25944393
TI  - Clathrin inhibitor Pitstop-2 disrupts the nuclear pore complex permeability
      barrier.
AB  - Existence of a selective nucleocytoplasmic permeability barrier is attributed to
      Phenylalanine-Glycine rich proteins (FG-nups) within the central channel of the
      nuclear pore complex (NPC). Limited understanding of the FG-nup structural
      arrangement hinders development of strategies directed at disrupting the NPC
      permeability barrier. In this report we explore an alternative approach to
      enhancing the NPC permeability for exogenous macromolecules. We demonstrate that
      the recently discovered inhibitor of clathrin coat assembly Pitstop-2 compromises
      the NPC permeability barrier in a rapid and effective manner. Treatment with
      Pitstop-2 causes a collapse of the NPC permeability barrier and a reduction of
      Importin beta binding accompanied by alteration of the NPC ultrastructure.
      Interestingly, the effects are induced by the same chemical agent that is capable
      of inhibiting clathrin-mediated endocytosis. To our knowledge, this is the first
      functional indication of the previously postulated evolutionary relation between
      clathrin and NPC scaffold proteins. 

PMID- 25944394
TI  - The role of brachytherapy in organ preservation for penile cancer: A meta
      analysis and review of the literature.
AB  - PURPOSE: A meta-analysis is presented comparing the overall survival (OS) and
      local control (LC) rates between penectomy and brachytherapy for penile cancer.
      METHODS AND MATERIALS: A PUBMED search was conducted with the MeSH terms, "penis,
      penile, cancer, brachytherapy, penectomy, surgery, treatment" in various
      combinations. Nineteen retrospective studies published between the years 1984
      2012, detailing OS and LC were included. Data were collected per Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: A
      total of 2178 males, median age 61 years, were included with 1505 in the surgery
      group and 673 in the brachytherapy group. The 5-year OS with surgery was 76%
      compared with 73% with brachytherapy, odds ratio = 1.17 (0.95-1.44, p = 0.128).
      Penectomy was associated with a higher 5-year LC rate of 84% compared with 79%
      with brachytherapy, odds ratio = 1.45 (1.09-1.92, p = 0.009). The organ
      preservation rate for brachytherapy treatment was 74%. Among the surgery patients
      in a Stage I/II subset, the 5-year OS and LC was 80% (n = 659) and 86% (n = 390),
      respectively. Of the 209 early stage patients who received brachytherapy, the 5
      year OS was 79% and LC was 84%. Chi-square testing demonstrated no difference for
      either OS or LC for early stage disease. CONCLUSIONS: This meta-analysis is
      limited by the retrospective nature and inherent selection bias of the data.
      While penectomy provided better control, there was no survival benefit, implying
      that in most cases failed brachytherapy could be salvaged with surgery.
      Additionally, in early stage tumors there was no survival or control difference.

PMID- 25944395
TI  - Dosimetric comparison of brachyablation and stereotactic ablative body
      radiotherapy in the treatment of liver metastasis.
AB  - PURPOSE: We compared the dosimetry of brachyablation (BA) and stereotactic
      ablative radiotherapy (SABR) in the treatment of liver metastases. METHODS AND
      MATERIALS: Treatment plans for 10 consecutive liver metastasis patients, treated
      with SABR, were replanned for BA. BA treatment was planned using five 12 Gy
      fractions to the same planning target volume (PTV) used for SABR. Dosimetric
      parameters were compared using a Student's paired t test. RESULTS AND
      CONCLUSIONS: BA and SABR plans had similar mean volume receiving 100% of the
      prescribed dose (94.1% vs. 93.9% of PTV, p = 0.8). Mean volume receiving 150% of
      the prescribed dose for BA was 63.6%, whereas for SABR it was 0. The minimum dose
      to the PTV was 65.8% for BA, whereas for SABR it was 87.4% (p = 0.0002). Liver
      volume receiving >=15 Gy was similar for BA and SABR (278 vs. 256 cc, p = 0.3).
      Small bowel mean dose, as percent prescription dose, was higher for BA (10.8% vs.
      7.1%, p = 0.006). Stomach mean dose was similar (4.9% vs. 4.8% of prescription
      dose, p = 0.98). Right kidney mean dose was greater for BA (6.7% vs. 4.2%, p =
      0.07). BA leads to a higher target dose, similar dose to organs at risk, but
      potentially with lower target coverage compared with SABR. Further work is needed
      to determine ideal suitability for mono vs. combination therapy with this
      approach.

PMID- 25944396
TI  - Clinicopathologic study of endolymphatic sac tumor (ELST) and differential
      diagnosis of papillary tumors located at the cerebellopontine angle.
AB  - We investigated the clinicopathologic features and immunophenotypes of 10 cases
      of endolymphatic sac tumor (ELST) and compared them with other papillary tumors,
      including eight cases of choroid plexus papilloma (CPP), three cases of atypical
      choroid plexus papilloma (ACPP), two cases of papillary ependymoma (PE), three
      cases of papillary meningioma (PM) and two cases of metastatic carcinoma (MC) the
      at cerebellopontine angle (CPA). The age at onset of ELST ranged from 13 to 39
      years. The male-to-female ratio was 1:1. The clinical presentations were
      primarily ear-related symptoms. The temporal bones showed extensive destruction.
      Histologically, the important characteristics for differential diagnosis with
      CPP, which is most similar to ELST, include the quantity of blood vessels, the
      nuclei location at apical surface of the papillary, clear cytoplasm cells
      sometimes with visible vacuoles, psammoma bodies and dura or bone invasion.
      Immunohistochemistry stains for AE1/AE3, cytokeratin CK)5/6, epithelial membrane
      antigen, CK8/18, S-100, and synaptophysin are helpful in diagnosis of ELST. In
      ELST, ultrastructure of uniform 2 MUm vesicles in cytoplasm was seen, and gene
      analysis also showed missense mutation in exon 3. This study indicates that the
      above histological features combined with immunohistochemistry findings are
      important for making the correct diagnosis. Gene analysis should be used in
      patients without medical history to exclude von Hippel-Lindau disease.

PMID- 25944400
TI  - Pit membrane structure is highly variable and accounts for a major resistance to
      water flow through tracheid pits in stems and roots of two boreal conifer
      species.
AB  - The flow of xylem sap in conifers is strongly dependent on the presence of a low
      resistance path through bordered pits, particularly through the pores present in
      the margo of the pit membrane. A computational fluid dynamics approach was taken,
      solving the Navier-Stokes equation for models based on the geometry of pits
      observed in tracheids from stems and roots of Picea mariana (black spruce) and
      Picea glauca (white spruce). Model solutions demonstrate a close, inverse
      relationship between the total resistance of bordered pits and the total area of
      margo pores. Flow through the margo was dominated by a small number of the widest
      pores. Particularly for pits where the margo component of flow resistance was low
      relative to that of the torus, pore location near the inner edge of the margo
      allowed for greater flow than that occurring through similar-sized pores near the
      outer edge of the margo. Results indicate a surprisingly large variation in pit
      structure and flow characteristics. Nonetheless, pits in roots have lower
      resistance to flow than those in stems because the pits were wider and consisted
      of a margo with a larger area in pores. 

PMID- 25944401
TI  - Allospecific CD4(+) T cells retain effector function and are actively regulated
      by Treg cells in the context of transplantation tolerance.
AB  - Although donor-specific transfusion (DST) plus CD154 blockade represents a robust
      protocol for inducing transplantation tolerance, the underlying mechanisms are
      incompletely understood. In a murine T-cell adoptive transfer model, we have
      visualized alloantigen-specific, TCR-transgenic for H2-A(b) /H2-K(d) 54-68
      epitope (TCR75) CD4(+) T cells with indirect allospecificity during the course of
      tolerance induction. Three main observations were made. First, although the
      majority of TCR75 CD4(+) T cells were deleted following DST plus CD154 blockade,
      the surviving TCR75 CD4(+) T cells were capable of making IL-2, upregulating
      CD44, and undergoing cell division, suggesting that they were functionally
      active. Indeed, residual TCR75 CD4(+) T cells reisolated from the primary
      recipients given DST plus CD154 blockade were fully capable of rejecting
      allografts upon secondary transfer. Second, in tolerant mice, TCR75 CD4(+) T
      cells were not induced to express Foxp3 in the graft-draining lymph node. TCR75
      CD4(+) T cells were also absent in accepted graft tissues in which endogenous
      Treg cells were enriched. Finally, DST plus CD154 blockade resulted in an
      abortive expansion of TCR75 CD4(+) T cells, a process that required the presence
      of endogenous Treg cells. Collectively, surviving TCR75 CD4(+) T cells are
      immunocompetent but kept in check by an endogenous immunosuppressive network
      induced by DST plus CD154 blockade.

PMID- 25944402
TI  - Peers experience of delivering a problem-solving programme to enhance
      antipsychotic medication adherence for individuals with schizophrenia.
AB  - ACCESSIBLE SUMMARY: No research has been conducted into the experience of peer
      support in improving adherence with oral antipsychotic medication for consumers
      with schizophrenia. Altruism influences peers to participate in peer support.
      Engagement in peer support can be challenging and rewarding for peers, and helps
      improve their own confidence and well-being. ABSTRACT: Many consumers with
      schizophrenia are reluctant to take their prescribed antipsychotic medications;
      however, non-adherence can lead to relapse. The aim of this study was to evaluate
      peers' perspectives of their participation in a problem-solving peer support
      programme to enhance adherence in consumers who are reluctant to take
      antipsychotic medication. Peers contacted consumers by a weekly telephone call
      for 8 weeks, and used a problem-solving approach to inform their discussion about
      medication adherence. Semi-structured qualitative interviews were used to
      evaluate peers' perspectives of their involvement in the programme. Three main
      themes were abstracted from the data: motivation to participate in the study,
      experience of peer support programme, and rewards and challenges of the peer
      experience. Helping others was an important motivator for peers in agreeing to
      participate in the study. Telephone delivery was a convenient way to deliver the
      peer support programme. However, at times, it was difficult to contact consumers
      by telephone and this caused some frustration. Despite these difficulties, peers
      recognized that being involved in the programme increased their confidence and
      made them feel worthwhile. The findings have implications for the use of peer
      support as an adjunct intervention to promote medication adherence in consumers
      with schizophrenia.

PMID- 25944404
TI  - Aggravation of Cerebral Oxygenation due to Intradialytic Hypotension Induced by
      Blood Volume Reduction During Hemodialysis: A Case Report.

PMID- 25944403
TI  - Osteoblasts Have a Neural Origin in Heterotopic Ossification.
AB  - BACKGROUND: Heterotopic ossification (HO) is the process of bone formation at a
      nonskeletal site. Recently, we showed that the earliest steps occur in sensory
      nerves. We now extend these studies by identifying unique osteogenic progenitors
      within the endoneurial compartment of sensory nerves. QUESTIONS/PURPOSES: We
      asked: (1) What is the nature of the osteoprogenitor in the endoneurium of
      peripheral nerves? (2) How do osteoprogenitors travel from the nerve to the site
      of new bone formation? METHODS: HO was induced by intramuscular injection of
      Ad5BMP-2-transduced cells in mice. Osteoprogenitors were identified through
      immunohistochemistry and then quantified and further characterized by
      fluorescence-activated cell sorting and immunocytochemistry. The kinetics of the
      appearance of markers of extravasation was determined by quantitative reverse
      transcription-polymerase chain reaction. In each experiment mice were injected
      with bone morphogenetic protein-2 (BMP-2)-producing cells (experimental) or with
      cells transduced with empty vector or, in some cases, a group receiving no
      injection (control). RESULTS: Induction of HO leads to the expression, within 24
      hours, of osteoblast-specific transcription factors in cells in the endoneurium
      followed by their coordinate disappearance from the nerve at 48 hours. They
      reappear in blood also at 48 hours after induction. During vessel entrance they
      begin to express the tight junction molecule, claudin 5. The cells expressing
      both the osteoblast-specific transcription factor, osterix, as well as claudin 5,
      then disappear from circulation at approximately 3 to 4 days by extravasation
      into the site of new bone formation. These endoneurial osteoprogenitors express
      neural markers PDGFRalpha, musashi-1, and the low-affinity nerve growth factor
      receptor p75(NTR) as well as the endothelial marker Tie-2. In a key experiment,
      cells that were obtained from mice that were injected with cells transduced with
      an empty vector, at 2 days after injection, contained 0.83% (SD, 0.07; 95%
      confidence interval [CI], 0.59-1.05) cells expressing claudin 5. However, cells
      that were obtained from mice 2 days after injection of BMP-2-producing cells
      contained 4.5% cells expressing claudin 5 (SD, 0.72%; 95% CI, 2.01-6.94; p <
      0.0015). Further analysis revealed that all of the cells expressing claudin 5
      were found to be positive for osteoblast-specific markers, whereas cells not
      expressing claudin 5 were negative for these same markers. CONCLUSIONS: The
      findings suggest that the endoneurial progenitors are the major osteogenic
      precursors that are used for HO. They exit the nerve through the endoneurial
      vessels, flow through vessels to the site of new bone formation, and then
      extravasate out of the vessels into this site. CLINICAL RELEVANCE: The biogenesis
      of osteoblasts in HO is very different than expected and shows that HO is, at
      least in part, a neurological disorder. This could result in a major shift in
      orthopaedic methodologies to prevent or treat this disease. The fact that nerves
      are intimately involved in the process may also provide clues that will lead to
      an explanation of the clinical fact that HO often occurs as a result of traumatic
      brain injury.

PMID- 25944405
TI  - Dominance of Giardia duodenalis assemblage A and Enterocytozoon bieneusi genotype
      BEB6 in sheep in Inner Mongolia, China.
AB  - To examine the occurrence and genotype distribution of Giardia duodenalis and
      Enterocytozoon bieneusi in sheep, fecal specimens were collected from 162 lambs
      and 213 ewes on seven farms in the Hulunbeier Prairie in Inner Mongolia, China.
      By PCR analysis of the triose-phosphate isomerase gene, 16 of the 375 (4.3%)
      specimens were positive for G. duodenalis, with 13 sequenced successfully
      belonging to assemblage A. Lambs had a significantly higher infection rate than
      ewes (8.6% versus 0.9%, respectively). The dominance of assemblage A in sheep was
      supported by PCR analysis of the beta-giardin and glutamate dehydrogenase genes;
      4 of 7 beta-giardin-positive specimens and 3 of 5 glutamate dehydrogenase
      positive specimens were identified as assemblage A. A much higher occurrence of
      E. bieneusi was detected by PCR analysis of the ribosomal internal transcribed
      spacer; 77.8% of lambs and 62.9% of ewes were positive for the pathogen. Two
      genotypes of E. bieneusi were found: BEB6 and CM7. Genotype BEB6 was seen in 237
      animals and on all seven farms, whereas genotype CM7 was detected in 23 animals
      from six farms. These data indicate that sheep in Inner Mongolia are commonly
      infected with G. duodenalis assemblage A and E. bieneusi genotype BEB6, two
      zoonotic pathogens in China. 

PMID- 25944406
TI  - Filarial infections in domestic dogs in Lusaka, Zambia.
AB  - Filariae are common parasites of dogs in many parts of the world, but little is
      known about the status of these infections in sub-Saharan Africa. A study was
      carried out to determine the occurrence and species of filariae among 272 dogs in
      Lusaka, Zambia. Giemsa stained blood smear and Knott's concentration methods
      revealed microfilariae in 16 (5.9%) of the dogs. PCR confirmed that most of these
      dogs had Acanthocheilonema reconditum infection. Ten (4.0%) of the examined dogs
      were positive for Dirofilaria immitis circulating antigen (by DiroCHEK((r))
      test), but D. immitis microfilariae were not identified in any of the dogs and
      the status of this infection remains unclear. Further studies are needed to
      explore the occurrence of filariae in Zambian dogs and the zoonotic potential for
      humans. 

PMID- 25944407
TI  - Application of the King's score as a prognostic model for hepatocellular
      carcinoma: still a long way to go.

PMID- 25944408
TI  - Discrimination of Semen cassiae from two related species based on the
      multivariate analysis of high-performance liquid chromatography fingerprints.
AB  - A simple and efficient high-performance liquid chromatography fingerprint method
      was developed to discriminate Semen cassiae from two related species: Cassia
      obtusifolia L. (CO) and Cassia tora L. (CT), the seeds of which are abbreviated
      as COS and CTS, respectively. 22 major bioactive ingredients in 42 samples (20
      COS and 22 CTS) collected from different provinces of China were identified. The
      statistical methods included similarity analysis and partial least-squares
      discriminant analysis. The pattern analysis method was specific and could be
      readily used for the comprehensive evaluation of Semen cassiae samples.
      Therefore, high-performance liquid chromatography fingerprint in combination with
      pattern analysis provided a simple and reliable method for discriminating between
      COS and CTS. 

PMID- 25944409
TI  - Epigenetic and Proteomic Expression Changes Promoted by Eating Addictive-Like
      Behavior.
AB  - An increasing perspective conceptualizes obesity and overeating as disorders
      related to addictive-like processes that could share common neurobiological
      mechanisms. In the present study, we aimed at validating an animal model of
      eating addictive-like behavior in mice, based on the DSM-5 substance use disorder
      criteria, using operant conditioning maintained by highly palatable chocolate
      flavored pellets. For this purpose, we evaluated persistence of food-seeking
      during a period of non-availability of food, motivation for food, and
      perseverance of responding when the reward was associated with a punishment. This
      model has allowed identifying extreme subpopulations of mice related to addictive
      like behavior. We investigated in these subpopulations the epigenetic and
      proteomic changes. A significant decrease in DNA methylation of CNR1 gene
      promoter was revealed in the prefrontal cortex of addict-like mice, which was
      associated with an upregulation of CB1 protein expression in the same brain area.
      The pharmacological blockade (rimonabant 3 mg/kg; i.p.) of CB1 receptor during
      the late training period reduced the percentage of mice that accomplished
      addiction criteria, which is in agreement with the reduced performance of CB1
      knockout mice in this operant training. Proteomic studies have identified
      proteins differentially expressed in mice vulnerable or not to addictive-like
      behavior in the hippocampus, striatum, and prefrontal cortex. These changes
      included proteins involved in impulsivity-like behavior, synaptic plasticity, and
      cannabinoid signaling modulation, such as alpha-synuclein, phosphatase 1-alpha,
      doublecortin-like kinase 2, and diacylglycerol kinase zeta, and were validated by
      immunoblotting. This model provides an excellent tool to investigate the
      neurobiological substrate underlying the vulnerability to develop eating
      addictive-like behavior. 

PMID- 25944411
TI  - Comparison of two different strategies of treatment with zoledronate in HIV
      infected patients with low bone mineral density: single dose versus two doses in
      2 years.
AB  - OBJECTIVES: Given the need for easily managed treatment of osteoporosis in HIV
      infected patients, we evaluated the efficacy and tolerability of two doses of
      zoledronate, by comparing three groups of patients: those with annual
      administration, those with biennial administration (one dose in 2 years) and a
      control group with no administration of zoledronate. METHODS: We randomized (2:1)
      31 patients on antiretroviral therapy with low bone mineral density (BMD) to
      zoledronate (5 mg administered intravenously; 21 patients) plus diet counselling
      and to a control group (diet counselling; 10 patients). At week 48, patients
      treated with zoledronate were randomized again to receive a second dose (two-dose
      group; n = 12) or to continue with diet counselling only (single-dose group; n =
      9). Changes in lumbar spine and hip BMD and bone turnover markers were compared.
      RESULTS: The median percentage change from baseline to week 96 in L1-L4 BMD was 
      1.74% [interquartile range (IQR) -2.56, 3.60%], 7.90% (IQR 4.20, 16.57%) and
      5.22% (IQR 2.02, 7.28%) in the control, two-dose and single-dose groups,
      respectively (P < 0.01, control vs. two doses; P = 0.02, control vs. single dose;
      P = 0.18, two doses vs. single dose). Hip BMD changed by a median of 2.12% (IQR 
      0.12, 3.08%), 5.16% (IQR 3.06, 6.74%) and 4.47% (IQR 1, 5.58%), respectively (P =
      0.04, control vs. two doses; P = 0.34, two doses vs. single dose). No differences
      between the two-dose and single-dose groups were detected in bone markers at week
      96. CONCLUSIONS: The benefits for BMD of a single dose of zoledronate in 2 years
      may be comparable to those obtained with two doses of the drug after 96 weeks,
      although this study is insufficiently powered to exclude a real difference.
      Future studies should explore whether biennial administration of zoledronate is a
      useful alternative in the treatment of osteoporosis in HIV-infected patients.

PMID- 25944410
TI  - Relating Intrinsic Low-Frequency BOLD Cortical Oscillations to Cognition in
      Schizophrenia.
AB  - The amplitude of low-frequency fluctuations (ALFF) in the blood oxygenation level
      dependent (BOLD) signal during resting-state fMRI reflects the magnitude of local
      low-frequency BOLD oscillations, rather than interregional connectivity. ALFF is
      of interest to studies of cognition because fluctuations in spontaneous intrinsic
      brain activity relate to, and possibly even constrain, task-evoked brain
      responses in healthy people. Lower ALFF has been reported in schizophrenia, but
      the cognitive correlates of these reductions remain unknown. Here, we assess
      relationships between ALFF and attention and working memory in order to establish
      the functional relevance of intrinsic BOLD oscillatory power alterations with
      respect to specific cognitive impairments in schizophrenia. As part of the
      multisite FBIRN study, resting-state fMRI data were collected from schizophrenia
      subjects (SZ; n=168) and healthy controls (HC; n=166). Voxelwise fractional ALFF
      (fALFF), a normalized ALFF measure, was regressed on neuropsychological measures
      of sustained attention and working memory in SZ and HC to identify regions
      showing either common slopes across groups or slope differences between groups
      (all findings p<0.01 height, p<0.05 family-wise error cluster corrected). Poorer
      sustained attention was associated with smaller fALFF in the left superior
      frontal cortex and bilateral temporoparietal junction in both groups, with
      additional relationships in bilateral posterior parietal, posterior cingulate,
      dorsal anterior cingulate (ACC), and right dorsolateral prefrontal cortex (DLPFC)
      evident only in SZ. Poorer working memory was associated with smaller fALFF in
      bilateral ACC/mPFC, DLPFC, and posterior parietal cortex in both groups. Our
      findings indicate that smaller amplitudes of low-frequency BOLD oscillations
      during rest, measured by fALFF, were significantly associated with poorer
      cognitive performance, sometimes similarly in both groups and sometimes only in
      SZ, in regions known to subserve sustained attention and working memory. Taken
      together, these data suggest that the magnitude of resting-state BOLD
      oscillations shows promise as a biomarker of cognitive function in health and
      disease. 

PMID- 25944412
TI  - How I manage cerebral vasculopathy in children with sickle cell disease.
AB  - Sickle cell disease induces specific brain alterations that involve both the
      macrocirculation and the microcirculation. The main overt neurovascular
      complications in children are infarctive stroke, transient ischaemic attack and
      cerebral haemorrhage. Silent cerebral infarction, cognitive dysfunction and
      recurrent headache are also common. Cerebrovascular disease selectively affects
      children with the HbSS or HbS-beta(0) genotypes (i.e. sickle cell anaemia). The
      incidence of stroke peaks between 2 and 5 years of age (1.02/100 patient-years)
      and increases with the severity of the anaemia. Most strokes can be prevented by
      annual transcranial Doppler screening from 2 to 16 years of age and providing
      chronic blood transfusion when this investigation shows elevated blood-flow
      velocities. The role for hydroxycarbamide in children with abnormal transcranial
      Doppler findings is under investigation. After a stroke, chronic blood
      transfusion is very strongly recommended, unless haematopoietic stem cell
      transplantation can be performed. Routine magnetic resonance imaging shows that
      more than one-third of children have silent cerebral infarction, which is
      associated with cognitive impairments. Screening for silent infarcts seems
      legitimate, since their presence may lead to supportive treatments. The role for
      more aggressive interventions such as hydroxycarbamide or chronic blood
      transfusion is debated. 

PMID- 25944413
TI  - Combined Effect of Thermosonication and Slightly Acidic Electrolyzed Water to
      Reduce Foodborne Pathogens and Spoilage Microorganisms on Fresh-cut Kale.
AB  - This study evaluated the efficacy of individual treatments (thermosonication
      [TS+DW] and slightly acidic electrolyzed water [SAcEW]) and their combination on
      reducing Escherichia coli O157:H7, Listeria monocytogenes, and spoilage
      microorganisms (total bacterial counts [TBC], Enterobacteriaceae, Pseudomonas
      spp., and yeast and mold counts [YMC]) on fresh-cut kale. For comparison, the
      antimicrobial efficacies of sodium chlorite (SC; 100 mg/L) and sodium
      hypochlorite (SH; 100 mg/L) were also evaluated. Each 10 g sample of kale leaves
      was inoculated to contain approximately 6 log CFU/g of E. coli O157:H7 or L.
      monocytogenes. Each inoculated or uninoculated samples was then dip treated with
      deionized water (DW; control), TS+DW, and SAcEW at various treatment conditions
      (temperature, physicochemical properties, and time) to assess the efficacy of
      each individual treatment. The efficacy of TS+DW or SAcEW was enhanced at 40 
      degrees C for 3 min, with an acoustic energy density of 400 W/L for TS+DW and
      available chlorine concentration of 5 mg/L for SAcEW. At 40  degrees C for 3 min,
      combined treatment of thermosonication 400 W/L and SAcEW 5 mg/L (TS+SAcEW) was
      more effective in reducing microorganisms compared to the individual treatments
      (SAcEW, SC, SH, and TS+DW) and combined treatments (TS+SC and TS+SH), which
      significantly (P < 0.05) reduced E. coli O157:H7, L. monocytogenes, TBC,
      Enterobacteriaceae, Pseudomonas spp., and YMC by 3.32, 3.11, 3.97, 3.66, 3.62,
      and >3.24 log CFU/g, respectively. The results suggest that the combined
      treatment of TS+SAcEW has the potential as a decontamination process in fresh-cut
      industry. 

PMID- 25944414
TI  - Efficacy of mepivacaine-tramadol combination on the success of inferior alveolar
      nerve blocks in patients with symptomatic irreversible pulpitis: a randomized
      clinical trial.
AB  - AIM: To compare the success of an inferior alveolar nerve block (IANB) after
      injecting a combination of mepivacaine and tramadol or mepivacaine alone in
      patients with symptomatic irreversible pulpitis (SIP) in mandibular permanent
      molars. METHODOLOGY: This study was a double-blind, randomized, controlled
      clinical trial. Two study groups were selected, each consisting of 28 patients
      who exhibited SIP on the first or second mandibular molars. All included patients
      presented with moderate-to-severe preoperative pain according to the modified
      Heft-Parker visual analogue scale (VAS). Patients were anaesthetized using the
      IANB technique employing identical cartridges that contained either 1.3 mL of 2%
      mepivacaine with epinephrine 1 : 100 000 plus 0.5 mL of tramadol 50 mg mL(-1)
      (experimental group) or 1.8 mL of 2% mepivacaine with epinephrine 1 : 100 000
      (control group). After 15 min, anaesthesia was evaluated by a progressive four
      test examination, that is numbness of the lip, positive or negative cold test,
      asymptomatic management of dental hard tissues and access to dental pulp. Success
      of the IANB was defined as the absence of pain during any of these evaluations.
      The data were analysed with a chi-square, Fisher's or Mann-Whitney U test.
      RESULTS: A total of 74 patients were initially assessed, with 56 patients
      eventually included and 18 excluded. No significant differences in age (P =
      0.384) or gender (P = 1) were found between the two groups. The success rates of
      anaesthesia with the IANB for the experimental and control groups were 57.1 and
      46.4%, respectively. The success rate of anaesthesia in the experimental group
      was not significantly different (P ? 0.05) from that of the control group. The
      duration of the anaesthetic effect was significantly longer for the experimental
      group (P = 0.026). CONCLUSION: The combination of mepivacaine-tramadol achieved
      similar success rates for IANB when compared to mepivacaine 2% epinephrine 1 :
      100 000. There was no significant difference in the anaesthetic efficacy between
      the control and experimental solutions, and none of the solutions tested were
      completely successful.

PMID- 25944415
TI  - Cost to government and society of chronic kidney disease stage 1-5: a national
      cohort study.
AB  - BACKGROUND: Costs associated with chronic kidney disease (CKD) are not well
      documented. Understanding such costs is important to inform economic evaluations
      of prevention strategies and treatment options. AIM: To estimate the costs
      associated with CKD in Australia. METHODS: We used data from the 2004/2005
      AusDiab study, a national longitudinal population-based study of non
      institutionalised Australian adults aged >=25 years. We included 6138
      participants with CKD, diabetes and healthcare cost data. The annual age and sex
      adjusted costs per person were estimated using a generalised linear model. Costs
      were inflated from 2005 to 2012 Australian dollars using best practice methods.
      RESULTS: Among 6138 study participants, there was a significant difference in the
      per-person annual direct healthcare costs by CKD status, increasing from $1829
      (95% confidence interval (CI): $1740-1943) for those without CKD to $14 545 (95%
      CI: $5680-44 842) for those with stage 4 or 5 CKD (P < 0.01). Similarly, there
      was a significant difference in the per-person annual direct non-healthcare costs
      by CKD status from $524 (95% CI: $413-641) for those without CKD to $2349 (95%
      CI: $386-5156) for those with stage 4 or 5 CKD (P < 0.01). Diabetes is a common
      cause of CKD and is associated with increased health costs. Costs per person were
      higher for those with diabetes than those without diabetes in all CKD groups;
      however, this was significant only for those without CKD and those with early
      stage (stage 1 or 2) CKD. CONCLUSION: Individuals with CKD incur 85% higher
      healthcare costs and 50% higher government subsidies than individuals without
      CKD, and costs increase by CKD stage. Primary and secondary prevention strategies
      may reduce costs and warrant further consideration.

PMID- 25944416
TI  - An efficient method to eliminate the protease activity contaminating commercial
      bovine pancreatic DNase I.
AB  - A method was developed to eliminate the proteases contaminating commercial DNase
      I, which can cause degradation of target protein during the purification process.
      Bio Basic DNase stock solution (in Tris-HCl buffer [pH 8.0] containing 5mM CaCl2)
      was first incubated at 50  degrees C to generate autolysis of proteases and
      zymogens, leading to a significant reduction in protease activity while
      preserving DNase activity. The residual protease activity was completely
      inhibited by further incubation with 2mM PMSF (phenylmethylsulfonyl fluoride) or
      2* S8830 inhibitor cocktail. This approach could be readily applicable to
      eliminate the protease activity in any DNase products or during the preparation
      of commercial DNase.

PMID- 25944417
TI  - A near-infrared fluorescence assay method to detect patulin in food.
AB  - Patulin (PAT) is a toxic secondary metabolite (mycotoxin) of different fungal
      species belonging to the genera Penicillium, Aspergillus, and Byssochlamys. They
      can grow on a large variety of food, including fruits, grains, and cheese. The
      amount of PAT in apple derivative products is a crucial issue because it is the
      measure of the quality of both the used raw products and the performed production
      process. Actually, all current methodologies used for the quantification of PAT
      are time-consuming and require skilled personnel beyond the sample pretreatment
      methods (e.g., high-performance liquid chromatography, mass spectrometry, and
      electrophoresis techniques). In this work, we present a novel fluorescence
      polarization approach based on the use of emergent near-infrared (NIR)
      fluorescence probes. The use of these fluorophores coupled to anti-PAT antibodies
      makes possible the detection of PAT directly in apple juice without any sample
      pretreatment. This methodology is based on the increase of fluorescence
      polarization emission of a fluorescence-labeled PAT derivative on binding to
      specific antibodies. A competition between PAT and the fluorescence-labeled PAT
      derivative allowed detecting PAT. The limit of detection of the method is 0.06
      MUg/L, a value that is lower than maximum residue limit of PAT fixed at 50 MUg/L
      from European Union regulation.

PMID- 25944418
TI  - Ovalbumin labeling with p-hydroxymercurybenzoate: The effect of different
      denaturing agents and the kinetics of reaction.
AB  - The aim of our study was to investigate how denaturing agents commonly used in
      protein analysis influence the labeling between a reactive molecule and proteins.
      For this reason, we investigated the labeling of ovalbumin (OVA) as a globular
      model protein with p-hydroxymercurybenzoate (pHMB) in its native state (phosphate
      buffer solution) and in different denaturing conditions (8 molL(-1) urea, 3 molL(
      1) guanidinium thiocyanate, 6 molL(-1) guanidinium chloride, 0.2% sodium dodecyl
      sulfate, and 20% methanol). In addition to chemical denaturation, thermal
      denaturation was also tested. The protein was pre-column simultaneously denatured
      and derivatized, and the pHMB-labeled denatured OVA complexes were analyzed by
      size exclusion chromatography (SEC) coupled online with chemical vapor generation
      atomic fluorescence spectrometry (CVG-AFS). The number of -SH groups titrated
      greatly depends on the protein structure in solution. Indeed, we found that,
      depending on the adopted denaturing conditions, OVA gave different aggregate
      species that influence the complexation process. The results were compared with
      those obtained by a common alternative procedure for the titration of -SH groups
      that employs monobromobimane (mBBr) as tagging molecule and molecular
      fluorescence spectroscopy as detection technique. We also investigated the
      labeling kinetics for denatured OVA and pHMB, finding that the 4 thiolic groups
      of OVA have a very different reactivity toward mercury labeling, in agreement
      with previous studies.

PMID- 25944419
TI  - Age-related Differences in Pre- and Post-synaptic Motor Cortex Inhibition are
      Task Dependent.
AB  - BACKGROUND: Previous research has shown age-related differences in short- (SICI)
      and long-interval intracortical inhibition (LICI) in both resting and active hand
      muscles, suggesting that healthy ageing influences post-synaptic motor cortex
      inhibition. However, it is not known how the ageing process effects the pre
      synaptic interaction of SICI by LICI, and how these pre- and post-synaptic
      intracortical inhibitory circuits are modulated by the performance of different
      motor tasks in older adults. OBJECTIVE: To examine age-related differences in pre
      and post-synaptic motor cortex inhibition at rest, and during index finger
      abduction and precision grip. METHODS: In 13 young (22.3 +/- 3.8 years) and 15
      old (73.7 +/- 4.0 years) adults, paired-pulse transcranial magnetic stimulation
      (TMS) was used to measure SICI (2 ms inter-stimulus interval; ISI) and LICI (100
      and 150 ms ISI), whereas triple-pulse TMS was used to investigate SICI when
      primed by LICI. RESULTS: We found no age-related difference in SICI at rest or
      during index finger abduction, but significantly greater SICI in older subjects
      during precision grip. Older adults showed reduced LICI in resting muscle (at an
      ISI of 150 ms), with no age-related differences in LICI during either task. When
      SICI was primed by LICI, disinhibition of motor cortex was reduced in older
      adults at rest (100 ms ISI) and during index finger abduction (150 ms ISI), but
      not during precision grip. CONCLUSIONS: Our results support age-related
      differences in pre- and post-synaptic motor cortex inhibition, which may
      contribute to impaired hand function during task performance in older adults.

PMID- 25944420
TI  - The effects of alpha-zearalanol on the proliferation of bone-marrow-derived
      mesenchymal stem cells and their differentiation into osteoblasts.
AB  - The aim of this study was to explore the effects of alpha-zearalanol (alpha-ZAL)
      on the proliferation of mouse bone-marrow-derived mesenchymal stem cells (BMSCs)
      and their differentiation into osteoblasts. Six- to eight-week-old BALB/C mice
      were used either as recipients or as bone marrow donors. BMSCs were isolated and
      collected using a differential adhesion method, with use of 10 % fetal bovine
      serum and Iscove's modified Dulbecco's medium. After the third generation, the
      BMSCs were randomly placed into the following subgroups: a control group, an
      osteogenic medium (OM) group, a 17beta-estradiol group, an alpha-ZAL 10(-7) mol/L
      group, an alpha-ZAL 10(-6) mol/L group, and an alpha-ZAL 10(-5) mol/L group. Flow
      cytometry was used to identify the BMSCs collected from the bone marrow. The 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test was performed,
      and markers of the osteoblasts were measured in the different subgroups. In
      addition, expression of osteoprotegerin and expression of receptor activator of
      nuclear factor kappaB ligand were examined using Western blot. In contrast to the
      control and OM groups, BMSCs in the alpha-ZAL groups exhibited long fusiform
      shapes, and contact inhibition was observed when the cells were closely packed.
      After induction, the BMSCs grew well and exhibited triangular, star, polygonal,
      or irregular shapes. Clumps and multiple cells were evident. The trends of the
      proliferation and differentiation for the control, OM, 17beta-estradiol, and
      alpha-ZAL groups were similar. Compared with the control and OM groups, in the
      alpha-ZAL groups the expression levels of alkaline phosphatase, procollagen type
      I N-terminal propeptide, bone morphogenetic protein 2, and osteocalcin were
      significantly increased (p < 0.05). In addition, alpha-ZAL inhibited
      osteoclastogenesis by increasing the expression of osteoprotegerin and decreasing
      the expression of nuclear factor kappaB ligand. In conclusion, alpha-ZAL can
      increase the proliferation of BMSCs and their differentiation into osteoblasts
      and can effectively suppress osteoclastogenesis. 

PMID- 25944422
TI  - Current Status of Thrombolytic Therapy in the Management of Prosthetic Valve
      Thrombosis.

PMID- 25944421
TI  - Effects of eldecalcitol on bone and skeletal muscles in glucocorticoid-treated
      rats.
AB  - Glucocorticoids cause secondary osteoporosis and myopathy, characterized by type
      II muscle fiber atrophy. We examined whether a new vitamin D3 analogue,
      eldecalcitol, could inhibit glucocorticoid-induced osteopenia or myopathy in
      rats, and also determined the effects of prednisolone (PSL) and/or eldecalcitol
      on muscle-related gene expression. Six-month-old female Wistar rats were
      randomized into four groups: PSL group (10 mg/kg PSL); E group (0.05 ug/kg
      eldecalcitol); PSL + E group; and control group. PSL, eldecalcitol, and vehicles
      were administered daily for 2 or 4 weeks. Right calf muscle strength, muscle
      fatigue, cross-sectional areas (CSAs) of left tibialis anterior muscle fibers,
      and bone mineral density (BMD) were measured following administration. Pax7,
      MyoD, and myogenin mRNA levels in gastrocnemius muscles were also determined.
      Muscle strength was significantly higher in the PSL + E group than in the PSL
      group (p < 0.05) after 4 weeks, but not after 2 weeks. No significant difference
      in muscle fatigue was seen between groups at 2 or 4 weeks. CSAs of type II muscle
      fibers were significantly larger in the E group and the PSL + E group than in the
      PSL group at 4 weeks (p = 0.0093, p = 0.0443, respectively). Eldecalcitol
      treatment for 4 weeks maintained the same BMD as the PSL + E group. After 2
      weeks, but not 4 weeks, eldecalcitol treatment significantly increased Pax7 and
      myogenin mRNA expression in gastrocnemius muscle, and PSL also stimulated
      myogenin expression. Eldecalcitol appears to increase muscle volume and to
      protect against femur BMD loss in PSL-administered rats, and it may also
      stimulate myoblast differentiation into early myotubes. 

PMID- 25944423
TI  - Locality, loneliness and lifestyle: a qualitative study of factors influencing
      women's health perceptions.
AB  - The contribution of women to the achievement of global public health targets
      cannot be underestimated. It is well evidenced that within families, women are a
      key influence on the health and well-being of their children and partners.
      However, geographical differences in women's health inequalities persist and
      research focusing specifically on women's perceptions of locality factors
      influencing their own health and well-being is scarce. This paper presents an
      interpretive, qualitative research study undertaken in 2011 with a group of women
      living in one locality in the North East of England in the United Kingdom which
      aimed to better understand their health and well-being perceptions and locality
      influences on it. Fifteen women participated in two focus groups and six
      individual, semi-structured interviews. Thematic analysis yielded four key
      themes: health and well-being perceptions; mental resilience; low income and
      choice; and influence of place. The influence of women's geographical location in
      relation to amenities and services and loneliness were recurring factors in the
      discussion, each influencing lifestyle. It was evident that women in their local
      context were themselves assets through which their own physical and mental health
      could be improved. However, women's perceptions of protective factors and their
      influences on health and well-being varied. Connecting with women in the context
      of their immediate living circumstances and understanding their perceptions as
      individuals are important first steps in the process of gaining consensus and
      mobilising their assets to collectively build healthy local communities.

PMID- 25944424
TI  - Tissue Velocities and Myocardial Deformation in Asymptomatic and Symptomatic
      Aortic Stenosis.
AB  - BACKGROUND: Assessment of myocardial longitudinal function has proved to be a
      sensitive marker of deteriorating myocardial function in aortic stenosis,
      demonstrated by both color Doppler tissue imaging and recently by two-dimensional
      speckle-tracking echocardiography. The aim of this study was to compare velocity
      (color Doppler tissue imaging) and deformation (two-dimensional speckle-tracking
      echocardiography) in relation to global and regional longitudinal function in
      asymptomatic and severe symptomatic aortic stenosis. METHODS: In a cross
      sectional design, 231 patients with aortic stenosis were divided into four
      groups: asymptomatic moderate aortic stenosis (aortic valve area, 1.0-1.5 cm(2);
      n = 38), asymptomatic severe aortic stenosis (aortic valve area < 1.0 cm(2); n =
      66), and symptomatic severe aortic stenosis with preserved (n = 68) and reduced
      (<50%) left ventricular ejection fraction (n = 59). RESULTS: Among all global
      (peak systolic s', diastolic e' and a', longitudinal displacement, and global
      longitudinal strain and strain rate) and regional longitudinal (basal, middle,
      and apical longitudinal strain and strain rate) parameters, only diastolic e',
      longitudinal displacement, and basal longitudinal strain (BLS) remained
      significantly associated with symptomatic status, independent of age, gender,
      heart rate, aortic valve area, stroke volume index, left ventricular mass index,
      left atrial volume index, and tricuspid annular systolic plane excursion.
      Furthermore, in a model with the aforementioned parameters, including e',
      longitudinal displacement, and BLS, only BLS remained significantly associated
      with symptomatic status in the entire study population (BLS per one-unit
      decrease: odds ratio, 1.23; 95% CI, 1.04-1.46; P = .017). Furthermore, patients
      with BLS < 13% were more likely to be symptomatic (odds ratio, 4.97; 95% CI, 2.6
      9.4; P < .001), and no patients with asymptomatic severe aortic stenosis with BLS
      >= 13% were admitted with myocardial infarction or heart failure during follow-up
      of 1,462 days. CONCLUSIONS: Among the many echocardiographic measures of
      longitudinal velocity and deformation, BLS has the strongest association with
      symptomatic status in aortic stenosis, and BLS < 13% is related to adverse
      outcomes in severe asymptomatic aortic stenosis.

PMID- 25944426
TI  - Lymphovascular invasion: a comprehensive appraisal in colon and rectal
      adenocarcinoma.
AB  - BACKGROUND: Colon and rectal adenocarcinomas differ at a multitude of levels. The
      association between outcome and predictor in 1 group may obscure the relationship
      between outcome and predictor in the other. OBJECTIVE: The current study aims to
      evaluate the prognostic properties of lymphovascular invasion in colon and rectal
      adenocarcinoma separately. MATERIALS AND METHODS (DESIGN, SETTING AND PATIENTS):
      A comparative retrospective analysis was undertaken to determine the prognostic
      properties of lymphovascular invasion in colon and rectal adenocarcinomas.
      Patients were classified as lymphovascular invasion positive and lymphovascular
      invasion negative in separate colon and rectal cancer cohorts. Within cohorts, a
      univariate analysis was undertaken to determine the association between
      lymphovascular invasion positivity and local/systemic recurrence and
      overall/disease-free survival. Findings were evaluated by using Kaplan-Meier
      estimates, log-rank analysis, and a Cox proportional hazards multivariate model.
      MAIN OUTCOME MEASURE: The primary outcomes measured were overall and disease-free
      survival. RESULTS: Five hundred twenty-seven patients were included in the
      analysis (379 with colon cancer and 148 with rectal cancer). On univariate
      analysis, lymphovascular invasion positivity was associated with adverse
      locoregional recurrence in colon (p = 0.002) but not rectal adenocarcinoma (p =
      0.13). Conversely, lymphovascular invasion positivity was associated with adverse
      systemic recurrence in rectal (p = 0.002) but not colon adenocarcinoma (p =
      0.35). On multivariate analysis, lymphovascular invasion positivity was an
      independent predictor of adverse disease-free survival in colon (p = 0.02) and
      rectal adenocarcinoma (p < 0.001). Regarding overall survival, lymphovascular
      invasion positivity was a poor prognostic indicator in rectal adenocarcinoma only
      (p = 0.04). LIMITATIONS AND CONCLUSIONS: In this retrospective analysis,
      lymphovascular invasion positivity was associated with different patterns of
      disease recurrence in colon and rectal cancer. Lymphovascular invasion positivity
      was associated with adverse overall survival in rectal cancer only.

PMID- 25944427
TI  - Selective approach for upper rectal cancer treatment: total mesorectal excision
      and preoperative chemoradiation are seldom necessary.
AB  - BACKGROUND: The implementation of preoperative chemoradiation combined with total
      mesorectal excision has reduced local recurrence rates in rectal cancer. However,
      the use of both types of treatment in upper rectal cancer is controversial.
      OBJECTIVE: The purpose of this work was to assess oncological results after
      radical resection of upper rectal cancers compared with sigmoid, middle, and
      lower rectal cancers and to determine risk factors for local recurrence in upper
      rectal cancer. DESIGN: This was a retrospective analysis of prospectively
      collected data. SETTINGS: This study was conducted in a tertiary care referral
      hospital in Valencia, Spain. PATIENTS: Analysis included 1145 patients who
      underwent colorectal resection with primary curative intent for primary sigmoid
      (n = 450), rectosigmoid (n = 70), upper rectal (n = 178), middle rectal (n =
      186), or lower rectal (n = 261) cancer. MAIN OUTCOME MEASURES: Oncological
      results, including local recurrence, disease-free survival, and cancer-specific
      survival, were compared between the different tumor locations. Univariate and
      multivariate analyses were performed to identify risk factors for local
      recurrence in upper rectal cancer. RESULTS: A total of 147 patients (82.6%) with
      upper rectal tumors underwent partial mesorectal excision, and only 10 patients
      (5.6%) of that group received preoperative chemoradiation. The 5-year actuarial
      local recurrence, disease-free survival, and cancer-specific survival rates for
      upper rectal tumors were 4.9%, 82.0%, and 91.6%. Local recurrence rates showed no
      differences when compared among all of the locations (p = 0.20), whereas disease
      free survival and cancer-specific survival were shorter for lower rectal tumors
      (p = 0.006; p = 0.003). The only independent risk factor for local recurrence in
      upper rectal cancer was an involved circumferential resection margin at
      pathologic analysis (HR, 14.23 (95% CI, 2.75-73.71); p = 0.002). LIMITATIONS:
      This was a single-institution, retrospective study. CONCLUSIONS: Most upper
      rectal tumors can be treated with partial mesorectal excision without the
      systematic use of preoperative chemoradiation. Involvement of the mesorectal
      fascia was the only independent risk factor for local recurrence in these tumors.

PMID- 25944425
TI  - Associations of Coronary Heart Disease with Common Carotid Artery Near and Far
      Wall Intima-Media Thickness: The Multi-Ethnic Study of Atherosclerosis.
AB  - BACKGROUND: Intima-media thickness (IMT) measured on ultrasound images of the
      common carotid artery (CCA) is associated with cardiovascular risk factors and
      events. Given the physics of ultrasound, CCA far wall IMT measurements are
      favored over near wall measurements, but this theoretical advantage is not well
      studied. METHODS: A total of 6,606 members of the Multi-Ethnic Study of
      Atherosclerosis, a longitudinal cohort study (mean age, 62.1 years; 52.7% women)
      who had near wall and far wall CCA IMT measurements. Multivariate linear
      regression models were used to estimate model goodness of fit of Framingham risk
      factors with near wall IMT, far wall IMT, and combined mean IMT. Multivariate Cox
      proportional hazards models were used to estimate hazard ratios for incident
      coronary heart disease events for each IMT variable. Change in Harrell's C
      statistic was used to compare the incremental value of each IMT variable when
      added to Framingham risk factors. RESULTS: Mean IMT had the strongest association
      with risk factors (R(2) = 0.31), followed by near wall (R(2) = 0.26) and far wall
      (R(2) = 0.22) IMT. Far wall IMT improved the prediction of coronary artery
      disease events over the Framingham risk factors (change in C statistic, 0.012;
      95% CI, 0.006-0.017; P < .001), as did mean IMT (P = .004), but near wall IMT did
      not. CONCLUSIONS: Far wall CCA IMT showed the strongest association with incident
      coronary heart disease, whereas mean IMT had the strongest associations with risk
      factors. This difference might affect the selection of appropriate IMT variables
      in different studies.

PMID- 25944428
TI  - Quantitative contribution of prognosticators to oncologic outcome after rectal
      cancer resection.
AB  - BACKGROUND: Prognostication is an important aspect of medical practice. It relies
      on statistical modeling testing the correlation of variables with the outcome of
      interest. OBJECTIVE: In contrast with the classic approach of predictive
      modeling, this study aimed to estimate the unique, individual, and relative
      contributions. This includes the quantitative contributions of patient-, tumor-,
      and treatment-related factors to oncologic outcome after rectal cancer resection.
      DESIGN: This was a retrospective analysis of prospectively registered data.
      SETTINGS: The study included 65 hospitals participating on a voluntary basis in
      the Project on Cancer of the Rectum, a Belgian multidisciplinary improvement
      project of rectal cancer care. PATIENTS: A total of 1470 patients presenting
      midrectal or low-rectal adenocarcinoma without distant metastasis were included.
      INTERVENTION: The study intervention was total mesorectal excision with or
      without sphincter preservation. MAIN OUTCOME MEASURES: The unique, individual,
      and relative contributions of a set of covariables to the statistical variability
      of the distant metastasis rate and overall survival have been calculated.
      RESULTS: The 5-year distant metastasis rate was 21% and overall survival 76%. A
      large amount of the variability of the outcomes (ie, 83.6% to 84.2%) could not be
      predicted by the prognostic factors. Unique contributions of the predictors
      ranged from 0.1% to 3.1%. The 3 risk factors with the highest unique contribution
      for distant metastasis were lymph node ratio, pathologic tumor stage, and total
      mesorectal quality; for overall survival they were age, lymph node ratio, and ASA
      score. LIMITATIONS: The main weakness of this study was incomplete participation
      and registration in the Project on Cancer of the Rectum. CONCLUSIONS: Several
      factors influence oncologic outcomes and are present in prediction models.
      However, the models predict relatively little of outcome variation.

PMID- 25944429
TI  - Surgical Treatment and Outcomes in Patients With Intestinal Behcet Disease: Long
      term Experience of a Single Large-Volume Center.
AB  - BACKGROUND: Few studies have examined the surgical treatment of intestinal Behcet
      disease. Consequently, there is currently no standard surgical treatment for
      intestinal Behcet disease. Instead, treatment is empirical and symptom based.
      OBJECTIVE: Our aim was to evaluate the clinical course after surgery and
      determine the appropriate surgical options for intestinal Behcet disease. DESIGN:
      Medical charts of patients who underwent surgery for intestinal Behcet were
      retrospectively reviewed. SETTINGS: The study was conducted at a tertiary
      referral center. PATIENTS: Ninety-one patients who underwent surgical treatment
      for intestinal Behcet disease between January 1995 and December 2012 were
      included in this study. MAIN OUTCOME MEASURES: Primary outcomes measured were
      patient demographics, clinical characteristics, operative and postoperative
      outcomes, and long-term follow-up data. RESULTS: Surgical treatment was mainly in
      response to intractability to medical treatment (56.0%), and 19.8% of patients
      underwent an emergency operation. Surgery was performed laparoscopically in 33.0%
      of the patients. Most patients received an ileocecectomy (39.6%) or a right
      hemicolectomy (34.1%). Twenty-eight patients (30.8%) experienced postoperative
      morbidities, and 8 patients (8.8%) required reoperations. There were 3 deaths.
      Reoperation was required for recurrent disease in 32 patients during the long
      term follow-up, and the 5-year cumulative reoperation rate was 31.2% (95% CI,
      20.4%-42.0%). Among those requiring a second operation, 53.1% were segmental
      colonic resections that included the previous anastomosis. From multivariable Cox
      regression analysis, independent predictors of surgical recurrence included
      postoperative use of steroids (HR = 2.85 (95% CI, 1.21-6.75); p = 0.02),
      postoperative complications (HR = 2.42 (95% CI, 1.12-5.22); p = 0.03), and BMI
      (HR per 1-kg/m increase in BMI = 0.90 (95% CI, 0.82-0.99); p = 0.04).
      LIMITATIONS: This study was designed retrospectively and had a small sample size.
      CONCLUSIONS: Patients treated surgically for intestinal Behcet disease frequently
      have postoperative complications and the need for a stoma and have a high risk of
      recurrence.

PMID- 25944430
TI  - Equivocal effect of intraoperative fluorescence angiography on colorectal
      anastomotic leaks.
AB  - BACKGROUND: Intraoperative fluorescence angiography is beneficial in several
      surgical settings to assess tissue perfusion. It is also used to assess bowel
      perfusion, but its role in improving outcomes in colorectal surgery has not been
      studied. OBJECTIVE: The purpose of this work was to determine whether
      intraoperative angiography decreases colorectal anastomotic leaks. DESIGN: This
      was a case-matched retrospective study in which patients were matched 1:1 with
      respect to sex, age, level of anastomosis, presence of a diverting loop
      ileostomy, and preoperative pelvic radiation therapy. SETTINGS: The study was
      conducted at an academic medical center. PATIENTS: Patients who underwent
      colectomy or proctectomy with primary anastomoses were included. INTERVENTIONS:
      The intraoperative use of fluorescence angiography to assess perfusion of the
      colon for anastomosis was studied. MAIN OUTCOME MEASURES: Anastomotic leak within
      60 days and whether angiography changed surgical management were the main
      outcomes measured. RESULTS: Case matching produced 173 pairs. The groups were
      also comparable with respect to BMI, smoking status, diabetes mellitus, surgical
      indications, and type of resection. In patients who had intraoperative
      angiography, 7.5% developed anastomotic leak, whereas 6.4% of those without
      angiography did (p value not significant). Univariate analysis revealed that
      preoperative pelvic radiation, more distal anastomosis, surgeon, and diverting
      loop ileostomy were positively associated with anastomotic leak. Multivariate
      analysis demonstrated that level of anastomosis and surgeon were associated with
      leaks. Poor perfusion of the proximal colon seen on angiography led to additional
      colon resection before anastomosis in 5% of patients who underwent intraoperative
      angiography. LIMITATIONS: The retrospective study design with the use of
      historical control subjects, selection bias, and small sample size were
      limitations to this study. CONCLUSIONS: Intraoperative fluorescence angiography
      to assess the perfusion of the colon conduit for anastomosis was not associated
      with colorectal anastomotic leak. Perfusion is but one of multiple factors
      contributing to anastomotic leaks. Additional studies are necessary to determine
      whether this technology is beneficial for colorectal surgery.

PMID- 25944431
TI  - Chlorhexidine with isopropyl alcohol versus iodine povacrylex with isopropyl
      alcohol and alcohol- versus nonalcohol-based skin preparations: the incidence of
      and readmissions for surgical site infections after colorectal operations.
AB  - BACKGROUND: Surgical site infections are a major cause of morbidity and mortality
      after colorectal operations. Preparation of the surgical site with antiseptic
      solutions is an essential part of wound infection prevention. To date, there is
      no universal consensus regarding which preparation is most efficacious.
      OBJECTIVE: This study compared 2.0% chlorhexidine with 70.0% isopropyl alcohol
      versus 0.7% iodine povacrylex with 74.0% isopropyl alcohol and alcohol-based
      versus nonalcohol-based skin preparations with regard to efficacy in preventing
      postoperative wound infections. DESIGN: This is a retrospective study from 2
      prospectively collected statewide databases combined. A propensity score model
      was used to adjust for differences between the groups in patient demographics,
      characteristics, comorbidities, and laboratory values. SETTINGS: The multicenter
      data set used in this analysis represents a variety of academic and community
      hospitals within the state of Michigan from January 2010 through June 2012.
      PATIENTS: Patients over the age of 18 years who underwent clean-contaminated
      colorectal operations were included. MAIN OUTCOME MEASURES: The incidence of
      superficial surgical site infections, any surgical site infection, any wound
      complication, and readmission within 30 days for surgical site infection were
      measured. RESULTS: When 2.0% chlorhexidine with 70.0% isopropyl alcohol (n = 425)
      and 0.7% iodine povacrylex with 74.0% isopropyl alcohol (n = 115) were compared,
      a total of 540 colorectal cases met inclusion criteria. When alcohol-based (n =
      610) and nonalcohol-based (n = 177) skin preparations were compared, a total of
      787 colorectal cases met inclusion criteria. There was no significant difference
      in the propensity-adjusted odds for having any of the 4 outcomes of interest when
      comparing 2.0% chlorhexidine with 70.0% isopropyl alcohol to 0.7% iodine
      povacrylex with 74.0% isopropyl alcohol and when comparing alcohol-based with
      nonalcohol-based skin preparations. LIMITATIONS: This was a nonrandomized study
      performed retrospectively based on data collected within the state of Michigan.
      CONCLUSIONS: The use of 2.0% chlorhexidine with 70.0% isopropyl alcohol versus
      0.7% iodine povacrylex with 74.0% isopropyl alcohol or alcohol-based versus
      nonalcohol-based skin preparations does not significantly influence the incidence
      of surgical site infections or readmission within 30 days for surgical site
      infection after clean-contaminated colorectal operations.

PMID- 25944432
TI  - Hospital volume and the occurrence of bleeding and perforation after colorectal
      endoscopic submucosal dissection: analysis of a national administrative database
      in Japan.
AB  - BACKGROUND: Colorectal endoscopic submucosal dissection has gained popularity as
      a minimally invasive technique for the treatment of colorectal neoplasms in many
      countries, including Japan. However, most previous studies of endoscopic
      submucosal dissection had relatively small sample sizes and only included
      patients treated at specialized centers. Associations between hospital volume and
      complication rates after colorectal endoscopic submucosal dissection are still
      poorly understood. OBJECTIVE: Our aim was to clarify the relationships between
      hospital volume and the occurrence rates of bleeding and perforation after
      colorectal endoscopic submucosal dissection. DESIGN: This was a retrospective
      cohort study. Hospital volume was defined as the number of colorectal endoscopic
      submucosal dissections performed at each hospital between April 2012 and March
      2013 and was categorized into the following quartiles: 1) very low-volume (18 or
      less patients during the year), 2) low-volume (19-35 patients), 3) high-volume
      (36-58 patients), and 4) very high-volume (59 or more). SETTINGS: This study was
      based on a national inpatient data from the Japanese Diagnosis Procedure
      Combination database. PATIENTS: A total of 7567 patients with colorectal
      endoscopic submucosal dissection were included. MAIN OUTCOME MEASURES: Severe
      postoperative bleeding requiring endoscopic hemostasis or blood transfusion
      within 1 week after endoscopic submucosal dissection and perforation requiring
      open surgery were the main outcomes measured. RESULTS: Severe postoperative
      bleeding and perforation occurred in 331 (4.4%) and 13 patients (0.2%).
      Multivariable logistic regression analysis showed that the very high hospital
      volume group had a significantly lower proportion of severe postoperative
      bleeding than the very low hospital volume group (OR = 0.48 [95 % CI, 0.27-0.83];
      p = 0.009). LIMITATIONS: This study lacked some information on clinicopathologic
      features including en bloc resection, curative resection, and relapse. Individual
      endoscopist experience could not be analyzed. CONCLUSIONS: The present study
      clearly showed a significant association between higher hospital volume and lower
      occurrence of severe postoperative bleeding.

PMID- 25944433
TI  - The ligation of the intersphincteric fistula tract procedure for anal fistula: a
      mixed bag of results.
AB  - BACKGROUND: The ligation of the intersphincteric fistula tract procedure, a
      sphincter-preserving technique, aims to obtain complete, durable healing, while
      preserving fecal continence in the treatment of transsphincteric anal fistulas.
      OBJECTIVE: This was a systematic review to evaluate the outcomes of the
      originally described (classic) ligation of the intersphincteric fistula tract
      procedure and the identified technical variations of the procedure. DATA SOURCES:
      PubMed, Web of Science, and the archive of Diseases of the Colon & Rectum were
      searched with the terms "ligation of intersphincteric fistula" and "ligation of
      intersphincteric fistula tract." STUDY SELECTION: Original, English-language
      studies reporting the primary healing rate for each technical variation of the
      ligation of the intersphincteric fistula tract procedure were included. Studies
      were excluded when the technique used was unclear or when primary healing rate
      was reported in a pooled manner including outcomes from multiple technical
      variations of the ligation of the intersphincteric fistula tract procedure.
      INTERVENTION: Outcomes associated with all of the technical variations of the
      ligation of the intersphincteric fistula tract procedure were investigated. MAIN
      OUTCOME MEASURES: The main outcome measured was primary healing rate. Secondary
      outcome measures included time to healing, changes in continence, and risk
      factors for failure. RESULTS: In all, 26 studies met criteria for review,
      including 1 randomized controlled trial and 25 cohort/case series. Seven
      technical variations of the ligation of the intersphincteric fistula tract
      procedure were identified and classified according to the surgical technique.
      Primary healing rates ranged from 47% to 95%. LIMITATIONS: The levels of evidence
      available in the published works are relatively low, as indicated by the Oxford
      Center for Evidence-Based Medicine evidence levels. CONCLUSIONS: The ligation of
      the intersphincteric fistula tract procedure is a promising treatment option for
      transsphincteric fistulas, with reasonable success rates and minimal impact on
      continence. The true efficacy of the procedure is unknown because of the number
      of technical variations and the pooled results reported in the literature.

PMID- 25944434
TI  - The D prefix: toward a reproducible validated alternative end point in rectal
      cancer.

PMID- 25944435
TI  - Tweaking the TNM Language for Rectal Cancer: A Slippery Slope.

PMID- 25944436
TI  - Preoperative Staging CT Thorax in Patients With Colorectal Cancer: Its Clinical
      Importance.

PMID- 25944437
TI  - The authors reply.

PMID- 25944438
TI  - The pelvic floor debates.

PMID- 25944439
TI  - Pelvic organ prolapse - a tailored approach.

PMID- 25944440
TI  - Impact of the United kingdom national bowel cancer awareness campaign on
      colorectal services.

PMID- 25944441
TI  - The author replies.

PMID- 25944444
TI  - Using the Ground Squirrel (Marmota bobak) as an Animal Model to Assess Monkeypox
      Drug Efficacy.
AB  - In experiments to study the sensitivity of ground squirrels (Marmota bobak) to
      monkeypox virus (MPXV) at intranasal challenge, expressed pox-like clinical
      symptoms (hyperthermia, lymphadenitis, skin rash all over the body and mucous
      membranes and others) were observed 7-9 days post-infection. The 50% infective
      dose (ID50 ) of MPXV for these marmots determined by the presence of clinical
      signs of the disease was 2.2 log10 PFU. Some diseased marmots (about 40%) died 13
      22 days post-infection, and the mortality rate was weakly dependent on MPXV
      infective dose. Lungs with trachea were primary target organs of marmots
      challenged intranasally (with ~30 ID50 ). The pathogen got to secondary target
      organs of the animals mainly via the lymphatic way (with replication in
      bifurcation lymph nodes). Lungs with trachea, nasal mucosa and skin were the
      organs where the maximum MPXV amounts accumulated in these animals. Evidences of
      the pathogen presence and replication were revealed in these and subcutaneously
      infected marmots in the traditional primary target cells for MPXV (macrophages
      and respiratory tract epitheliocytes), as well as in some other cells
      (endotheliocytes, plasmocytes, fibroblasts, reticular and smooth muscle cells).
      Our use of this animal species to assess the antiviral efficacy of some drugs
      demonstrated the agreement of the obtained results with those described in
      scientific literature, which opens up the prospects of using marmots as animal
      models for monkeypox to develop therapeutic and preventive anti-smallpox drugs.

PMID- 25944445
TI  - Developmentally dynamic genome: Evidence of genetic influences on increases and
      decreases in conduct problems from early childhood to adolescence.
AB  - The development of conduct problems in childhood and adolescence is associated
      with adverse long-term outcomes, including psychiatric morbidity. Although genes
      constitute a proven factor of stability in conduct problems, less is known
      regarding their role in conduct problems' developmental course (i.e. systematic
      age changes, for instance linear increases or decreases).Mothers rated conduct
      problems from age 4 to 16 years in 10,038 twin pairs from the Twins Early
      Development Study. Individual differences in the baseline level (.78; 95% CI: .68
      .88) and the developmental course of conduct problems (.73; 95% CI: .60-.86) were
      under high and largely independent additive genetic influences. Shared
      environment made a small contribution to the baseline level but not to the
      developmental course of conduct problems. These results show that genetic
      influences not only contribute to behavioural stability but also explain
      systematic change in conduct problems. Different sets of genes may be associated
      with the developmental course versus the baseline level of conduct problems. The
      structure of genetic and environmental influences on the development of conduct
      problems suggests that repeated preventive interventions at different
      developmental stages might be necessary to achieve a long-term impact. 

PMID- 25944447
TI  - Looking and listening: A comparison of intertrial repetition effects in visual
      and auditory search tasks.
AB  - Previous research shows that performance on pop-out search tasks is facilitated
      when the target and distractors repeat across trials compared to when they
      switch. This phenomenon has been shown for many different types of visual
      stimuli. We tested whether the effect would extend beyond visual stimuli to the
      auditory modality. Using a temporal search task that has previously been shown to
      elicit priming of pop-out with visual stimuli (Yashar & Lamy, Psychological
      Science, 21(2), 243-251, 2010), we showed that priming of pop-out does occur with
      auditory stimuli and has characteristics similar to those of an analogous visual
      task. These results suggest that either the same or similar mechanisms might
      underlie priming of pop-out in both modalities. 

PMID- 25944446
TI  - The enzyme activities of Caf1 and Ccr4 are both required for deadenylation by the
      human Ccr4-Not nuclease module.
AB  - In eukaryotic cells, the shortening and removal of the poly(A) tail
      (deadenylation) of cytoplasmic mRNA is a key event in regulated mRNA degradation.
      A major enzyme involved in deadenylation is the Ccr4-Not deadenylase complex,
      which can be recruited to its target mRNA by RNA-binding proteins or the miRNA
      repression complex. In addition to six non-catalytic components, the complex
      contains two enzymatic subunits with ribonuclease activity: Ccr4 and Caf1 (Pop2).
      In vertebrates, each deadenylase subunit is encoded by two paralogues: Caf1,
      which can interact with the anti-proliferative protein BTG2, is encoded by CNOT7
      and CNOT8, whereas Ccr4 is encoded by the highly similar genes CNOT6 and CNOT6L.
      Currently, it is unclear whether the catalytic subunits work co-operatively or
      whether the nuclease components have unique roles in deadenylation. We therefore
      developed a method to express and purify a minimal human BTG2-Caf1-Ccr4 nuclease
      sub-complex from bacterial cells. By using chemical inhibition and well
      characterized inactivating amino acid substitutions, we demonstrate that the
      enzyme activities of Caf1 and Ccr4 are both required for deadenylation in vitro.
      These results indicate that Caf1 and Ccr4 cooperate in mRNA deadenylation and
      suggest that the enzyme activities of Caf1 and Ccr4 are regulated via allosteric
      interactions within the nuclease module. 

PMID- 25944449
TI  - Multisensory top-down sets: Evidence for contingent crossmodal capture.
AB  - Numerous studies that have investigated visual selective attention have
      demonstrated that a salient but task-irrelevant stimulus can involuntarily
      capture a participant's attention. Over the years, a lively debate has erupted
      concerning the impact of contingent top-down control settings on such stimulus
      driven attentional capture. In the research reported here, we investigated
      whether top-down sets would also affect participants' performance in a
      multisensory task setting. A nonspatial compatibility task was used, in which the
      target and the distractor were always presented sequentially from the same
      spatial location. We manipulated target-distractor similarity by varying the
      visual and tactile features of the stimuli. Participants always responded to the
      visual target features (color); the tactile features were incorporated into the
      participants' top-down set only when the experimental context allowed for the
      tactile feature to be used in order to discriminate the target from the
      distractor. Larger compatibility effects after bimodal distractors were observed
      only when the participants were searching for a bimodal target and when tactile
      information was useful. Taken together, these results provide the first
      demonstration of nonspatial contingent crossmodal capture. 

PMID- 25944448
TI  - Modeling one-choice and two-choice driving tasks.
AB  - An experiment is presented in which subjects were tested on both one-choice and
      two-choice driving tasks and on non-driving versions of them. Diffusion models
      for one- and two-choice tasks were successful in extracting model-based measures
      from the response time and accuracy data. These include measures of the quality
      of the information from the stimuli that drove the decision process (drift rate
      in the model), the time taken up by processes outside the decision process and,
      for the two-choice model, the speed/accuracy decision criteria that subjects set.
      Drift rates were only marginally different between the driving and non-driving
      tasks, indicating that nearly the same information was used in the two kinds of
      tasks. The tasks differed in the time taken up by other processes, reflecting the
      difference between them in response processing demands. Drift rates were
      significantly correlated across the two two-choice tasks showing that subjects
      that performed well on one task also performed well on the other task.
      Nondecision times were correlated across the two driving tasks, showing common
      abilities on motor processes across the two tasks. These results show the
      feasibility of using diffusion modeling to examine decision making in driving and
      so provide for a theoretical examination of factors that might impair driving,
      such as extreme aging, distraction, sleep deprivation, and so on. 

PMID- 25944450
TI  - Visual space perception at different levels of depth description.
AB  - The main purpose of this study was to determine the effect of the depth
      description levels required in experimental tasks on visual space perception. Six
      observers assessed the locations of 11 posts by determining a distance ranking
      order, comparing the distances between posts with a reference unit, and
      estimating the absolute distances between the posts. The experiments were
      performed in an open outdoor field under normal daylight conditions with posts at
      distances ranging from 2 to 12 m. To directly assess and compare the observers'
      perceptual performance in all three phases of the experiment, the raw data were
      transformed to common measurement levels. A pairwise comparison analysis provided
      nonmetric information regarding the observers' relative distance judgments, and a
      multidimensional-scaling procedure provided metric information regarding the
      relationship between a perceived spatial layout and the layout of the actual
      scene. The common finding in all of the analyses was that the precision and
      consistency of the observers' ordinal distance judgments were greater than those
      of their ratio distance judgments, which were, in turn, greater than the
      precision and consistency of their absolute-magnitude distance judgments. Our
      findings raise questions regarding the ecological validity of standard
      experimental tasks.

PMID- 25944451
TI  - Automatic capture of attention by conceptually generated working memory
      templates.
AB  - Many theories of attention propose that the contents of working memory (WM) can
      act as an attentional template, which biases processing in favor of perceptually
      similar inputs. While support has been found for this claim, it is unclear how
      attentional templates are generated when searching real-world environments. We
      hypothesized that in naturalistic settings, attentional templates are commonly
      generated from conceptual knowledge, an idea consistent with sensorimotor models
      of knowledge representation. Participants performed a visual search task in the
      delay period of a WM task, where the item in memory was either a colored disk or
      a word associated with a color concept (e.g., "Rose," associated with red).
      During search, we manipulated whether a singleton distractor in the array matched
      the contents of WM. Overall, we found that search times were impaired in the
      presence of a memory-matching distractor. Furthermore, the degree of impairment
      did not differ based on the contents of WM. Put differently, regardless of
      whether participants were maintaining a perceptually colored disk identical to
      the singleton distractor, or whether they were simply maintaining a word
      associated with the color of the distractor, the magnitude of attentional capture
      was the same. Our results suggest that attentional templates can be generated
      from conceptual knowledge, in the physical absence of the visual feature. 

PMID- 25944452
TI  - Sensitivity and specificity for detecting early glaucoma in eyes with high myopia
      from normative database of macular ganglion cell complex thickness obtained from
      normal non-myopic or highly myopic Asian eyes.
AB  - PURPOSE: We aimed to determine the sensitivity and specificity of the normative
      database of non-myopic and highly myopic eyes of the macular ganglion cell
      complex (mGCC) thickness embedded in the NIDEK RS-3000 spectral-domain optical
      coherence tomography (SD-OCT) for detecting early glaucoma in highly myopic eyes.
      METHODS: Forty-seven highly myopic eyes (axial length >=26.0 mm) of 47 subjects
      were studied. The SD-OCT images were used to determine the mGCC thickness within
      a 9-mm diameter circle centered on the fovea. The sensitivity and specificity of
      the non-myopic database were compared to that of the highly myopic database for
      distinguishing the early glaucomatous eyes from the non-glaucomatous eyes. The
      mGCC scans were classified as abnormal if at least one of the eight sectors of
      the significance map was < 1 % of the normative thickness. RESULTS: Twenty-one
      eyes were diagnosed to be non-glaucomatous and 26 eyes to have early glaucoma. .
      The average mGCC thickness was significantly thinner (80.9 +/- 8.5 MUm) in the
      early glaucoma group than in the non-glaucomatous group (91.2 +/- 7.5 MUm; p <1 *
      10(-4)). The sensitivity was 96.2 % and specificity was 47.6 % when the non
      myopic database was used, and the sensitivity was 92.3 % and the specificity was
      90.5 % when the highly myopic database was used. The difference in the
      specificity was significant (p < 0.01). CONCLUSIONS: The significantly higher
      specificity of the myopic normative database for detecting early glaucoma in
      highly myopic eyes will lead to fewer false positive diagnoses. The database
      obtained from highly myopic eyes should be used when evaluating the mGCC
      thickness of highly myopic eyes.

PMID- 25944454
TI  - The importance of providing trauma-informed care in alcohol and other drug
      services.

PMID- 25944453
TI  - Does treatment have an impact on incidence and risk factors for autism spectrum
      disorders in children with infantile spasms?
AB  - OBJECTIVE: Infantile spasms (IS) are a severe form of childhood epilepsy
      associated with autism spectrum disorders (ASD) in up to 35% of cases. The
      objective of this post hoc analysis of our randomized control trial was to
      determine whether rapid diagnosis and treatment of IS could limit the incidence
      of ASD while identifying risk factors related to ASD outcome. METHODS: Patients
      with IS were randomized in a standardized diagnostic and treatment protocol.
      Clinical and electroencephalogram (EEG) evaluations were completed at all eight
      visits over 5 years, while cognitive evaluations were administered at 0, 6, 24
      and 60 months, respectively. Autism was initially screened by means of the
      Checklist for Autism in Toddlers (CHAT) at 24 months, and formally assessed at
      the 30-and 60-month follow-ups using the Autism Diagnostic Observation Schedule
      Generic (ADOS-G). RESULTS: Of the 69 patients included in the study, 25 could not
      be assessed due to severe delay or death. Eleven of the 42 patients screened with
      CHAT, were found to be at risk of an ASD outcome. ADOS was performed in 44 and 10
      were diagnosed with ASD. The CHAT proved to correlate highly with the ADOS (80%
      ppv). Only patients with symptomatic IS developed ASD (p = 0.003). Earlier
      diagnosis or successful treatment did not correlate with a reduced rate of ASD.
      Other risk factors were identified such as having chronic epileptic discharges in
      the frontotemporal areas after disappearance of hypsarrhythmia (p = 0.005 and p =
      0.007) and being of nonwhite origin (p = 0.009). SIGNIFICANCE: ASD was only
      observed in children with sympyomatic IS. Other clinical risk factors include
      chronic frontotemporal epileptic activity and being of non-white origin. Early
      diagnosis and treatment did not prevent ASD as an outcome of IS. However,
      patients at risk for ASD could be identified early on and should in the future
      benefit from early intervention to potentially improve their long-term outcome.

PMID- 25944455
TI  - Breathing Techniques Affect Female but Not Male Hip Flexion Range of Motion.
AB  - Two protocols were undertaken to help clarify the effects of breathing techniques
      on hamstrings (hip flexion) range of motion (ROM). The protocols examined effects
      of breathing conditions on ROM and trunk muscle activity. Protocol 1: Thirty
      recreationally active participants (15 male, 15 female, 20-25 years) were
      monitored for changes in single-leg raise (SLR) ROM with 7 breathing conditions
      before or during a passive supine SLR stretch. Breathing conditions included
      prestretch inhale, prestretch exhale, inhale-during stretch, exhale-during
      stretch, neutral, hyperventilation, and hypoventilation before stretch. Protocol
      2: Eighteen recreationally active participants (9 male, 9 female, 20-25 years)
      were monitored for electromyographic (EMG) activity of the rectus abdominus,
      external obliques, lower abdominal stabilizers, and lower erector spinae while
      performing the 7 breathing conditions before or during a passive SLR stretch.
      Control exhibited less ROM (p = 0.008) than the prestretch inhale (7.7%), inhale
      during stretch (10.9%), and hypoventilation (11.2%) conditions with females.
      Protocol 3: Greater overall muscle activity in the prestretch exhale condition
      was found compared with inhale-during stretch (43.1%?; p = 0.029) and
      hypoventilation (51.2%?; p = 0.049) conditions. As the inhale-during stretch and
      hypoventilation conditions produced the lowest levels of muscle activity for both
      sexes and the highest ROM for the females, it can be assumed that both mechanical
      and neural factors affect female SLR ROM. Lesser male ROM might be attributed to
      anatomical differences such as greater joint stiffness. The breathing techniques
      may have affected intra-abdominal pressure, trunk muscle cocontractions, and
      sympathetic neural activity to enhance female ROM.

PMID- 25944456
TI  - Changes in Running Performance After Four Weeks of Interval Hypoxic Training in
      Australian Footballers: A Single-Blind Placebo-Controlled Study.
AB  - There is a paucity of data examining the impact of high-intensity interval
      hypoxic training (IHT) on intermittent running performance. This study assessed
      the effects of IHT on 17 amateur Australian Footballers, who completed 8 interval
      treadmill running sessions (IHT [FIO2 = 15.1%] or PLACEBO) over 4 weeks, in
      addition to normoxic football (2 per week) and resistance (2 per week) training
      sessions. To match relative training intensity, absolute IHT intensity reduced by
      6% of normoxic vV[Combining Dot Above]O2peak compared with PLACEBO. Before and
      after the intervention, performance was assessed by Yo-Yo intermittent recovery
      test level 2 (Yo-Yo IR2) and a self-paced team sport running protocol.
      Standardized effect size statistics were calculated using Cohen's d to compare
      between the interventions. Compared with PLACEBO, IHT subjects experienced (a)
      smaller improvements in Yo-Yo IR2 performance (Cohen's d = -0.42 [-0.82 to -0.02;
      90% confidence interval]); (b) similar increases in high-intensity running
      distance during the team sport protocol (d = 0.17 [-0.50 to 0.84]); and (c)
      greater improvements in total distance (d = 0.72 [0.33-1.10]) and distance
      covered during low-intensity activity (d = 0.59 [-0.07 to 1.11]) during the team
      sport protocol. The lower absolute training intensity of IHT may explain the
      smaller improvements in Yo-Yo IR2 performance in the hypoxic group. Conversely,
      the data from the self-paced protocol suggest that IHT may positively influence
      pacing strategies in team sport athletes. In conclusion, IHT alters pacing
      strategies in team sport athletes (i.e., increased distance covered during low
      intensity activity). However, IHT leads to smaller improvements in externally
      paced high-intensity intermittent running performance (i.e., Yo-Yo IR2), which
      may be related to a reduced absolute training intensity during IHT sessions.

PMID- 25944457
TI  - Carry-Over of Force Production Symmetry in Athletes of Differing Strength Levels.
AB  - This study sought to determine the level of association between bilateral force
      production symmetry assessment methods (standing weight distribution [WtD],
      unloaded and lightly loaded jumps, and isometric strength) and to determine
      whether the amount of symmetry carry-over between these tasks differs for strong
      and weak athletes. Subjects for this study included male (n = 31) and female (n =
      32) athletes from National Collegiate Athletic Association Division I sports.
      Athletes performed WtD, unloaded and lightly loaded (20 kg) static and
      countermovement jumps, and isometric midthigh pull (IMTP) assessments on 2
      adjacent force plates. Ground reaction force data were used to calculate symmetry
      variables and performance-related variables. Using Pearson zero order
      correlations, evaluations of the amount of symmetry carry-over were made. Weight
      distribution correlated strongly with jump peak force (PF) (r = 0.628-0.664).
      Strong relationships were also observed between loading conditions for jump
      variables (r = 0.568-0.957) as were the relationships between jump types for PF,
      peak power, and net impulse (r = 0.506-0.834). Based on the pooled sample, there
      was a lack of association between IMTP and WtD for jump symmetry variables.
      However, when examining strong and weak groups, rate of force development showed
      moderate to strong symmetry carry-over in the strongest athletes (r = 0.416
      0.589). Stronger athletes appear to display similar explosive strength symmetry
      characteristics in dynamic and isometric assessments, unlike weaker athletes.
      Strength seems to influence the amount of force production symmetry carry-over
      between bilateral assessments. There may be optimal loads and variables for
      symmetry assessment, but these may differ based on population characteristics.

PMID- 25944458
TI  - Cognitive emotion regulation: characteristics and effect on quality of life in
      women with breast cancer.
AB  - BACKGROUND: In recent decades, researchers and clinicians have sought to
      determine how to improve the quality of life (QOL) of women with breast cancer.
      Previous research has shown that many women have particular behavioral coping
      styles, which are important determinants of QOL. As behavior is closely
      associated with cognition, these patients may also have particular cognitive
      coping styles. However, the cognitive coping characteristics and their effects on
      QOL in women with breast cancer remain unclear. Thus, this study aimed to
      characterize cognitive coping styles among women with breast cancer and explore
      the effects of cognitive emotion regulation strategies on QOL. METHODS: The
      Chinese version of the Cognitive Emotion Regulation Questionnaire was used to
      assess cognitive coping strategies in 665 women newly diagnosed with breast
      cancer and 662 healthy women. QOL of patients was assessed using the Functional
      Assessment of Cancer Therapy for Breast Cancer Scale. Independent-samples t-tests
      were performed to investigate group differences in reporting of cognitive coping
      strategies. Multiple regression analyses were performed to examine the effects of
      cognitive coping strategies on QOL in patients after controlling for
      sociodemographic and medical variables. RESULTS: Compared with control subjects,
      patients reported less frequent use of self-blame, rumination, positive
      refocusing, refocusing on planning, positive reappraisal, and blaming others, and
      more frequent use of acceptance and catastrophizing (all p < 0.01). The three
      strongest predictors of group membership were catastrophizing (B = -0.35),
      acceptance (B = -0.29), and positive reappraisal (B = 0.23). All nine coping
      strategies were significantly correlated with QOL in patients (all p < 0.05).
      After controlling for sociodemographic and medical variables, self-blame,
      rumination, and catastrophizing negatively affected QOL (all p < 0.05), whereas
      acceptance and positive reappraisal had positive effects (all p < 0.01).
      CONCLUSIONS: Compared with healthy women, women newly diagnosed with breast
      cancer use catastrophizing and acceptance more frequently, and positive
      reappraisal, self-blame, rumination, positive refocusing, refocusing on planning,
      and blaming others less frequently. Catastrophizing, rumination, and self-blame
      may be not conducive to QOL of women with breast cancer and acceptance and
      positive reappraisal may be useful.

PMID- 25944459
TI  - Neuropathological sequelae of Human Immunodeficiency Virus and apathy: A review
      of neuropsychological and neuroimaging studies.
AB  - Apathy remains a common neuropsychiatric disturbance in the Human
      Immunodeficiency Virus (HIV-1) despite advances in anti-retroviral treatment
      (ART). The goal of the current review is to recapitulate findings relating apathy
      to the deleterious biobehavioral effects of HIV-1 in the post-ART era. Available
      literatures demonstrate that the emergence of apathy with other neurocognitive
      and neuropsychiatric symptoms may be attributed to neurotoxic effects of viral
      proliferation, e.g., aggregative effect of Tat and gp120 on apoptosis, transport
      and other enzymatic reactions amongst dopaminergic neurons and neuroglia. An
      assortment of neuroimaging modalities converge on the severity of apathy symptoms
      associated with the propensity of the virus to replicate within frontal-striatal
      brain circuits that facilitate emotional processing. Burgeoning research into
      functional brain connectivity also supports the effects of microvascular and
      neuro-inflammatory injury linked to aging with HIV-1 on the presentation of
      neuropsychiatric symptoms. Summarizing these findings, we review domains of HIV
      associated neurocognitive and neuropsychiatric impairment linked to apathy in
      HIV. Taken together, these lines of research suggest that loss of affective,
      cognitive and behavioral inertia is commensurate with the neuropathology of HIV
      1. 

PMID- 25944460
TI  - Does prescription of medical compression prevent development of post-thrombotic
      syndrome after proximal deep venous thrombosis?
AB  - AIM: The aim of this review is to try to explain the controversy by critical
      analysis of previously published randomized controlled trials on the value of
      elastic compression stockings in the treatment of acute proximal deep vein
      thrombosis in prevention of post-thrombotic syndrome, which forms the scientific
      basis for our present management. METHODS: A research was made through Medline
      and Embase databases to identify relevant original articles, not abstracts, with
      the following keywords: post-thrombotic syndrome, deep venous thrombosis, venous
      thromboembolism, compression stockings, prevention and compliance. RESULTS: We
      identified five randomized controlled trials (RCTs) before the SOX trial
      including 798 patients with acute proximal deep vein thrombosis. Brandjes (1997):
      at two years' follow-up, elastic compression stockings reduced post-thrombotic
      syndrome by 50%;Ginsberg (2001): no difference in post-thrombotic syndrome with
      or without elastic compression stockings after more than two years' follow
      up;Partsch (2004): elastic compression stockings with routine above knee and
      early ambulation reduced the incidence and severity of post-thrombotic syndrome
      after two years' follow-up;Prandoni (2004) showed significantly less post
      thrombotic syndrome after elastic compression stockings for two years with a five
      year follow-up;Aschwanden (2008) showed no difference with elastic compression
      stockings after three years' follow-up. CONCLUSION: Prescription of elastic
      compression stockings for the prevention of post-thrombotic syndrome is now in
      doubt. Immediate compression after diagnosis of acute deep vein thrombosis to
      prevent swelling and reduce pain, permitting early ambulation in combination with
      adequate anticoagulation has proven benefit, although a secondary analysis of the
      SOX trial refutes this belief. Continued long-term compression treatment is
      questioned. Two major questions remain:Is the lack of positive outcome on the
      development of post-thrombotic syndrome after proximal deep vein thrombosis due
      to the fact that there were a few patients with iliofemoral extension in the
      quoted randomized controlled trials who may benefit from prolonged medical
      compression treatment?Compliance is the major issue, and the two randomized
      controlled trials with excellent control of compliance showed significant
      reduction in the rate of post-thrombotic syndrome, but we know that in daily
      practice the adherence is closer to Kahn's data.

PMID- 25944461
TI  - Anticoagulation strategies for primary percutaneous coronary intervention:
      current controversies and recommendations.

PMID- 25944462
TI  - The long wait for a breakthrough in chronic fatigue syndrome.

PMID- 25944463
TI  - Use of BIS VISTA bilateral monitor for diagnosis of intraoperative seizures, a
      case report.
AB  - Changes in BIS (bispectral index) VISTA bilateral monitoring system associated
      with intraoperative episodes of generalized and focal seizures, during total
      intravenous anesthesia for resection of a left frontal parasagittal meningioma,
      are herein described.

PMID- 25944464
TI  - Partial trisomy of 11q23.3-q25 inherited from a maternal low-level mosaic
      unbalanced translocation.
AB  - Partial trisomy of 11q is characterized by pre/postnatal growth retardation,
      microcephaly, dysmorphic craniofacial features, cognitive disability, abnormal
      muscle tone, inguinal hernia, and possible congenital heart defects. Here, we
      describe a 17-year-old male with a 17.77 Mb-sized [arr 11q23.3-q25 (116,667,559 
      134,434,130) *3] partial trisomy resulting from the unbalanced translocation
      between chromosomes 11 and 22. The terminal translocation was detected using
      oligonucleotide array comparative genomic hybridization (CGH) with fluorescence
      in situ hybridization (FISH) confirmation. The partial trisomy was inherited from
      his mother who had the low-level (22.7%) mosaic unbalanced translocation and a
      normal phenotype. The patient showed most of the common features of partial
      trisomy 11q syndrome, with additional findings, including mesenteric
      fibromatosis.

PMID- 25944465
TI  - Downregulation of miR-375 in aldosterone-producing adenomas promotes tumour cell
      growth via MTDH.
AB  - OBJECTIVE: Previous studies have investigated the genetic and molecular basis of
      primary aldosteronism (PA), a common cause of human hypertension, but the effects
      of microRNAs (miRNAs) on the adrenocortical cell proliferation and aldosterone
      production are largely obscure. Here, we characterized miRNA expression patterns
      in the subtypes of PA to gain a better understanding of its pathogenesis.
      METHODS: miRNA expression was assessed by microarray profiling analysis in
      aldosterone-producing adenoma (APA), unilateral adrenal hyperplasia (UAH) and
      normal adrenal cortex tissues. Selected differentially expressed miRNAs were
      further validated in a validation cohort by qRT-PCR. A gain-of-function approach
      was used to explore the functional role of the specific miRNA in vitro. RESULTS:
      Of 31 miRNAs including miR-375, miR-7 and miR-29b were found to be significantly
      differentially expressed among these three groups. miR-375 was the most
      downregulated one in adrenal cortex tissues from PA patients, and its expression
      level was inversely correlated with the tumour size in APA. Overexpression of miR
      375 in a human adrenocortical cell line (H295R) reduced cell proliferation and
      suppressed the expression of MTDH (metadherin, also known as astrocyte elevated
      gene-1). Moreover, MTDH was verified as a direct target of miR-375 through
      luciferase reporter assays. Knock-down of MTDH in H295R cells attenuated Akt
      Ser473 phosphorylation and inhibited cell viability. CONCLUSION: Our findings
      suggest that miR-375 exerts its tumour-suppressive function via targeting
      MTDH/Akt pathway and implicate a potential therapeutic target in PA.

PMID- 25944466
TI  - The population genomic signature of environmental selection in the widespread
      insect-pollinated tree species Frangula alnus at different geographical scales.
AB  - The evaluation of the molecular signatures of selection in species lacking an
      available closely related reference genome remains challenging, yet it may
      provide valuable fundamental insights into the capacity of populations to respond
      to environmental cues. We screened 25 native populations of the tree species
      Frangula alnus subsp. alnus (Rhamnaceae), covering three different geographical
      scales, for 183 annotated single-nucleotide polymorphisms (SNPs). Standard
      population genomic outlier screens were combined with individual-based and
      multivariate landscape genomic approaches to examine the strength of selection
      relative to neutral processes in shaping genomic variation, and to identify the
      main environmental agents driving selection. Our results demonstrate a more
      distinct signature of selection with increasing geographical distance, as
      indicated by the proportion of SNPs (i) showing exceptional patterns of genetic
      diversity and differentiation (outliers) and (ii) associated with climate. Both
      temperature and precipitation have an important role as selective agents in
      shaping adaptive genomic differentiation in F. alnus subsp. alnus, although their
      relative importance differed among spatial scales. At the 'intermediate' and
      'regional' scales, where limited genetic clustering and high population diversity
      were observed, some indications of natural selection may suggest a major role for
      gene flow in safeguarding adaptability. High genetic diversity at loci under
      selection in particular, indicated considerable adaptive potential, which may
      nevertheless be compromised by the combined effects of climate change and habitat
      fragmentation. 

PMID- 25944467
TI  - Three hundred years of low non-paternity in a human population.
AB  - When cuckoldry is frequent we can expect fathers to withhold investment in
      offspring that may not be theirs. Human paternal investment can be substantial
      and is in line with observations from tens of thousands of conceptions that
      suggest that cuckoldry is rare in humans. The generality of this claim seems to
      be in question as the rate of cuckoldry varies across populations and studies
      have mostly been on Western populations. Two additional factors complicate our
      conclusions, (1) current estimates of the rate of cuckoldry in humans may not
      reflect our past behaviour as adultery can be concealed by the use of
      contraceptives; and (2) it is difficult to obtain samples that are random with
      respect to their paternity certainty. Studies that combine genealogies with Y
      chromosome haplotyping are able to circumvent some of these problems by probing
      into humans' historical behaviour. Here we use this approach to investigate 1273
      conceptions over a period of 330 years in 23 families of the Afrikaner population
      in South Africa. We use haplotype frequency and diversity and coalescent
      simulations to show that the male population did not undergo a severe bottleneck
      and that paternity exclusion rates are high for this population. The rate of
      cuckoldry in this Western population was 0.9% (95% confidence interval 0.4-1.5%),
      and we argue that given the current data on historical populations we have to
      conclude that, at least for Western human populations, cuckoldry rate is probably
      in the range of 1%. 

PMID- 25944468
TI  - Commensalism facilitates gene flow in mountains: a comparison between two Rattus
      species.
AB  - Small mammal dispersal is strongly affected by geographical barriers. However,
      commensal small mammals may be passively transported over large distances and
      strong barriers by humans (often with agricultural products). This pattern should
      be especially apparent in topographically complex landscapes, such as mountain
      ranges, where valleys and/or peaks can limit dispersal of less vagile species. We
      predict that commensal species would have lower genetic differentiation and
      higher migration rates than related non-commensals in such landscapes. We
      contrasted population genetic differentiation in two sympatric Rattus species (R.
      satarae and R. rattus) in the Western Ghats mountains in southern India. We
      sampled rats from villages and adjacent forests in seven locations (20-640 km
      apart). Capture-based statistics confirmed that R. rattus is abundant in human
      settlements in this region, whereas R. satarae is non-commensal and found mostly
      in forests. Population structure analyses using ~970-bp mitochondrial control
      region and 17 microsatellite loci revealed higher differentiation for the non
      commensal species (R. satarae F-statistics=0.420, 0.065, R. rattus F
      statistics=0.195, 0.034; mitochondrial DNA, microsatellites, respectively).
      Genetic clustering analyses confirm that clusters in R. satarae are more distinct
      and less admixed than those in R. rattus. R. satarae shows higher slope for
      isolation-by-distance compared with R. rattus. Although mode of migration
      estimates do not strongly suggest higher rates in R. rattus than in R. satarae,
      they indicate that migration over long distances could still be higher in R.
      rattus. We suggest that association with humans could drive the observed pattern
      of differentiation in the commensal R. rattus, consequently impacting not only
      their dispersal abilities, but also their evolutionary trajectories. 

PMID- 25944470
TI  - Is it time to use minimal residual disease to stratify post-remission treatment
      for acute myeloid leukemia?

PMID- 25944471
TI  - MYC in diffuse large B-cell lymphoma: always the bad guy?

PMID- 25944472
TI  - The variation game: Cracking complex genetic disorders with NGS and omics data.
AB  - Tremendous advances in Next Generation Sequencing (NGS) and high-throughput omics
      methods have brought us one step closer towards mechanistic understanding of the
      complex disease at the molecular level. In this review, we discuss four basic
      regulatory mechanisms implicated in complex genetic diseases, such as cancer,
      neurological disorders, heart disease, diabetes, and many others. The mechanisms,
      including genetic variations, copy-number variations, posttranscriptional
      variations, and epigenetic variations, can be detected using a variety of NGS
      methods. We propose that malfunctions detected in these mechanisms are not
      necessarily independent, since these malfunctions are often found associated with
      the same disease and targeting the same gene, group of genes, or functional
      pathway. As an example, we discuss possible rewiring effects of the cancer
      associated genetic, structural, and posttranscriptional variations on the protein
      protein interaction (PPI) network centered around P53 protein. The review
      highlights multi-layered complexity of common genetic disorders and suggests that
      integration of NGS and omics data is a critical step in developing new
      computational methods capable of deciphering this complexity. 

PMID- 25944469
TI  - Analysis of class I and II histone deacetylase gene expression in human leukemia.
AB  - Histone deacetylase (HDAC) inhibitors are well-characterized anti-leukemia agents
      and HDAC gene expression deregulation has been reported in various types of
      cancers. This study sought to characterize HDAC gene expression patterns in
      several types of leukemia. To do so, a systematic study was performed of the mRNA
      expression of all drug-targetable HDACs for which reagents were available. This
      was done by real-time PCR in 24 leukemia cell lines and 39 leukemia patients,
      which included AML, MDS and CLL patients, some of whom received HDAC inhibitor
      treatment. Among the samples analyzed, there was no discernible pattern in HDAC
      expression. HDAC expression was generally increased in CLL patients, except for
      HDAC2 and HDAC4. HDAC expression was also generally increased in VPA-treated
      MOLT4 cells. However, this increased expression was not seen in AML patients
      treated with vorinostat. In summary, increased HDAC expression was noted in CLL
      patients in general, but the HDAC expression patterns in myeloid malignancies
      appear to be heterogeneous, which implies that the role of HDACs in leukemia may
      be related to global expression or protein function rather than specific
      expression patterns. 

PMID- 25944473
TI  - Dietary Supplementation of Walnut Partially Reverses 1-Methyl-4-phenyl-1,2,3,6
      tetrahydropyridine Induced Neurodegeneration in a Mouse Model of Parkinson's
      Disease.
AB  - Numerous studies indicating that natural plant sources and their active
      phytochemicals offer protection to the pathological processes related to the
      development of neurogenerative diseases including Parkinson's disease (PD). In
      the present study, the neuro protective efficacy of dietary supplementation of
      walnut (6 %) for 28 days was examined in 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) (i.p., 20 mg/kg body weight/day) for last four
      consecutive days. MPTP injection diminished the levels of GSH, dopamine and
      metabolites along with decreased activities of GPx and mitochondrial complex I.
      Further, the levels of TBARS and enzymatic antioxidants such as SOD and catalase,
      MAO-B activities were enhanced by MPTP treatment. Behavioral deficits and lowered
      TH expression are also proved MPTP induced neurotoxicity. Dietary supplementation
      of walnut attenuated MPTP-induced impairment in PD mice might be by its MAO-B
      inhibitory, antioxidant and mitochondrial protective actions. To find out the
      exact mechanism of action walnut on PD mice warrants further extensive studies.

PMID- 25944474
TI  - Electroencephalographic (EEG) Photoparoxysmal Responses Under 5 Years of Age:
      Diagnostic Implications and Peculiarities.
AB  - Electroencephalographic (EEG) photoparoxysmal response has been little
      investigated in very young patients. We studied 5055 patients aged less than 5
      years with no acquired brain damage, who underwent EEG recording. We determined
      the prevalence and significance of photoparoxysmal response induced by 1 to 20 Hz
      photic stimulation. Fifty-three showed photoparoxysmal response and were
      diagnosed as having Dravet syndrome (11), epileptic encephalopathy with myoclonic
      seizures (8), neurodegenerative disorders (8), benign idiopathic epilepsies (9),
      and static disorders with a known or suspected genetic origin (17).
      Photoparoxysmal response occurred in response to 1 to 5 Hz trains in 41.5%
      subjects. In most patients with epileptic encephalopathies, photoparoxysmal
      response was a transient finding: in 53.2%, it failed to be replicated in the
      recordings performed more than 6 months after initial evaluation. Photoparoxysmal
      response is rare in patients aged less than 5 years and has some peculiarities
      such as occurrence with low-frequency stimuli. Its distribution in specific
      conditions indicates that photoparoxysmal response may be useful in diagnostic
      workup. 

PMID- 25944475
TI  - A Falsification of the Citation Impediment in the Taxonomic Literature.
AB  - Current science evaluation still relies on citation performance, despite
      criticisms of purely bibliometric research assessments. Biological taxonomy
      suffers from a drain of knowledge and manpower, with poor citation performance
      commonly held as one reason for this impediment. But is there really such a
      citation impediment in taxonomy? We compared the citation numbers of 306
      taxonomic and 2291 non-taxonomic research articles (2009-2012) on mosses,
      orchids, ciliates, ants, and snakes, using Web of Science (WoS) and correcting
      for journal visibility. For three of the five taxa, significant differences were
      absent in citation numbers between taxonomic and non-taxonomic papers. This was
      also true for all taxa combined, although taxonomic papers received more
      citations than non-taxonomic ones. Our results show that, contrary to common
      belief, taxonomic contributions do not generally reduce a journal's citation
      performance and might even increase it. The scope of many journals rarely
      featuring taxonomy would allow editors to encourage a larger number of taxonomic
      submissions. Moreover, between 1993 and 2012, taxonomic publications accumulated
      faster than those from all biological fields. However, less than half of the
      taxonomic studies were published in journals in WoS. Thus, editors of highly
      visible journals inviting taxonomic contributions could benefit from taxonomy's
      strong momentum. The taxonomic output could increase even more than at its
      current growth rate if: (i) taxonomists currently publishing on other topics
      returned to taxonomy and (ii) non-taxonomists identifying the need for taxonomic
      acts started publishing these, possibly in collaboration with taxonomists.
      Finally, considering the high number of taxonomic papers attracted by the journal
      Zootaxa, we expect that the taxonomic community would indeed use increased
      chances of publishing in WoS indexed journals. We conclude that taxonomy's
      standing in the present citation-focused scientific landscape could easily
      improve-if the community becomes aware that there is no citation impediment in
      taxonomy. 

PMID- 25944476
TI  - Heterogeneous Rates of Molecular Evolution and Diversification Could Explain the
      Triassic Age Estimate for Angiosperms.
AB  - Dating analyses based on molecular data imply that crown angiosperms existed in
      the Triassic, long before their undisputed appearance in the fossil record in the
      Early Cretaceous. Following a re-analysis of the age of angiosperms using updated
      sequences and fossil calibrations, we use a series of simulations to explore the
      possibility that the older age estimates are a consequence of (i) major shifts in
      the rate of sequence evolution near the base of the angiosperms and/or (ii) the
      representative taxon sampling strategy employed in such studies. We show that
      both of these factors do tend to yield substantially older age estimates. These
      analyses do not prove that younger age estimates based on the fossil record are
      correct, but they do suggest caution in accepting the older age estimates
      obtained using current relaxed-clock methods. Although we have focused here on
      the angiosperms, we suspect that these results will shed light on dating
      discrepancies in other major clades. 

PMID- 25944477
TI  - Dynamic evolution and biogenesis of small RNAs during sex reversal.
AB  - Understanding origin, evolution and functions of small RNA (sRNA) genes has been
      a great challenge in the past decade. Molecular mechanisms underlying sexual
      reversal in vertebrates, particularly sRNAs involved in this process, are largely
      unknown. By deep-sequencing of small RNA transcriptomes in combination with
      genomic analysis, we identified a large amount of piRNAs and miRNAs including
      over 1,000 novel miRNAs, which were differentially expressed during gonad
      reversal from ovary to testis via ovotesis. Biogenesis and expressions of miRNAs
      were dynamically changed during the reversal. Notably, phylogenetic analysis
      revealed dynamic expansions of miRNAs in vertebrates and an evolutionary
      trajectory of conserved miR-17-92 cluster in the Eukarya. We showed that the miR
      17-92 cluster in vertebrates was generated through multiple duplications from
      ancestor miR-92 in invertebrates Tetranychus urticae and Daphnia pulex from the
      Chelicerata around 580 Mya. Moreover, we identified the sexual regulator Dmrt1 as
      a direct target of the members miR-19a and -19b in the cluster. These data
      suggested dynamic biogenesis and expressions of small RNAs during sex reversal
      and revealed multiple expansions and evolutionary trajectory of miRNAs from
      invertebrates to vertebrates, which implicate small RNAs in sexual reversal and
      provide new insight into evolutionary and molecular mechanisms underlying sexual
      reversal. 

PMID- 25944478
TI  - Outcomes of pancreatic surgery in patients older than 70 years.
AB  - INTRODUCTION: The proportion of elderly patients is growing rapidly. Knowing the
      results of pancreatic surgery in this group of patients would help surgeons to
      make therapeutic decisions. The objective is to evaluate the surgical outcomes of
      pancreatic resections in patients over 70 years. METHODS: Retrospective study
      including patients undergoing pancreatic resection during the period 2009-2014.
      The sample was divided into 2 groups. G1: Patients under 70 years and G2:
      Patients older than 70 years. Surgical results between the 2 groups were
      evaluated. RESULTS: Seventy three pancreatic resections were performed, 51 (70%)
      patients belonged to G1 and 22 (30%) to G2. There were no significant differences
      between G1 and G2 in terms of operative time and hospitalization days. No
      significant difference was obtained in the incidence of delayed gastric emptying,
      pancreatic fistula or biliary fistula. The overall mortality in the series was
      4.1% showing difference between both groups, with 2% in G1 and 13.6% in G2
      (P=.04). When a sub-analysis in G2 was made, mortality in this group occurred
      only in patients with significant comorbidities with ASA >= 3 (P=.004). Both
      groups with oncologic disease had similar overall survival and disease-free
      survival. CONCLUSIONS: Age should not be a limiting factor for pancreatic
      resections. The elderly have similar results as younger patients and their
      increased perioperative mortality is due to the presence of important associated
      comorbidities rather than age as an independent risk factor.

PMID- 25944480
TI  - Editorial Comment to Immunoglobulin G4-related disease in the urinary bladder.

PMID- 25944479
TI  - Effect of microgravity on glial cell line-derived neurotrophic factor and
      cerebral dopamine neurotrophic factor gene expression in the mouse brain.
AB  - Mice were exposed to 1 month of space flight on the Russian biosatellite BION-M1
      to determine its effect on the expression of genes involved in the maintenance of
      the mouse brain dopamine system. The current article focuses on the genes
      encoding glial cell line-derived neurotrophic factor (GDNF) and cerebral dopamine
      neurotrophic factor (CDNF). Space flight reduced expression of the GDNF gene in
      the striatum and hypothalamus but increased it in the frontal cortex and raphe
      nuclei area. At the same time, actual space flight reduced expression of the gene
      encoding CDNF in the substantia nigra but increased it in the raphe nuclei area.
      To separate the effects of space flight from environmental stress contribution,
      we analyzed expression of the investigated genes in mice housed for 1 month on
      Earth in the same shuttle cabins that were used for space flight and in mice of
      the vivarium control group. Shuttle cabin housing failed to alter the expression
      of the GDNF and CDNF genes in the brain structures investigated. Thus, actual
      long-term space flight produced dysregulation in genetic control of GDNF and CDNF
      genes. These changes may be related to downregulation of the dopamine system
      after space flight, which we have shown earlier. (c) 2015 Wiley Periodicals, Inc.
      SIGNIFICANCE: Our results provide the first evidence of microgravity effects on
      expression of the GDNF and CDNF neurotrophic factor genes. A considerable
      decrease in mRNA level of GDNF and CDNF in the nigrostriatal dopamine system was
      found. Because both GDNF and CDNF play a significant role in maintenance and
      survival of brain dopaminergic neurons, we can assume that this dysregulation in
      genetic control of GDNF and CDNF genes in substantia nigra could be among the
      reasons for the deleterious effects of space flight on the dopamine system.

PMID- 25944481
TI  - Pinus sylvestris switches respiration substrates under shading but not during
      drought.
AB  - Reduced carbon (C) assimilation during prolonged drought forces trees to rely on
      stored C to maintain vital processes like respiration. It has been shown,
      however, that the use of carbohydrates, a major C storage pool and apparently the
      main respiratory substrate in plants, strongly declines with decreasing plant
      hydration. Yet no empirical evidence has been produced to what degree other C
      storage compounds like lipids and proteins may fuel respiration during drought.
      We exposed young scots pine trees to C limitation using either drought or shading
      and assessed respiratory substrate use by monitoring the respiratory quotient,
      delta(13) C of respired CO2 and concentrations of the major storage compounds,
      that is, carbohydrates, lipids and amino acids. Only shaded trees shifted from
      carbohydrate-dominated to lipid-dominated respiration and showed progressive
      carbohydrate depletion. In drought trees, the fraction of carbohydrates used in
      respiration did not decline but respiration rates were strongly reduced. The
      lower consumption and potentially allocation from other organs may have caused
      initial carbohydrate content to remain constant during the experiment. Our
      results suggest that respiratory substrates other than carbohydrates are used
      under carbohydrate limitation but not during drought. Thus, respiratory substrate
      shift cannot provide an efficient means to counterbalance C limitation under
      natural drought. 

PMID- 25944483
TI  - Managing and caring for distressed and disturbed service users: the thoughts and
      feelings experienced by a sample of English mental health nurses.
AB  - This paper reports the thoughts and feelings experienced by registered mental
      health nurses caring for distressed and/or disturbed service users in acute
      inpatient psychiatric settings in England. The prevailing thoughts of nurses were
      of cognitive dissonance and the conflict between benevolence and malevolence if
      coercive measures were seen as negative rather than positive; prevailing feelings
      experienced by nurses were fear, anxiety and vulnerability. To enhance care
      quality, nurses expressed the need for better communication with service users,
      and preventing the use of coercive measures and promotion of alternative methods
      of care and management. The nurses considered that debriefing dialogues following
      untoward incidents, practice development initiatives, education and training
      together with clinical supervision could be the way forward. The paper builds on
      the existing literature in offering clear explanations of nurses' thoughts and
      feelings when caring for distressed and/or disturbed service users in an English
      acute, inpatient psychiatric setting. Despite the small sample size and the
      limitations that it generates, the study findings will be of interest to the
      wider mental health nursing community. The findings will link to other national
      and international studies and therefore be valuable for future research studies
      of this kind. Collectively, they are building up a general picture of the
      distress, cognitive and emotional dissonance experienced by mental health nurses
      when using coercive interventions. The findings will help to develop mental
      health nurse education and enhance practice. High levels of distress and
      disturbance among service users experiencing acute mental illness is a major
      problem for mental health nurses (MHNs). The thoughts and feelings experienced by
      these nurses when caring for service users are of paramount importance as they
      influence clinical practice and caregiving. Similarly to research by other
      countries, this paper reports national, qualitative data regarding the thoughts
      and feelings of English MHNs who care for these service users within acute
      inpatient psychiatric settings. Data were collected from focus groups in which
      MHNs working in acute inpatient settings in England participated and analysed
      using inductive content analysis. Findings highlighted three broad themes: (1)
      emotional and cognitive dissonance; (2) therapeutic engagement; and (3)
      organizational management and support. The prevailing thoughts of nurses were of
      cognitive dissonance and the conflict between benevolence and malevolence if
      coercive measures were seen as negative rather than positive; the prevailing
      feelings experienced by nurses were fear, anxiety and vulnerability. Nurses would
      like better communication with service users, prevention of coercive measures and
      the use of alternative methods of care and/or management to ensure enhanced care.
      Participants considered practice development initiatives, education, training,
      staff and managerial support including debriefing and clinical supervision as the
      way forward. Despite the small sample size and its limitations, these national
      data add to the existing literature, and the study findings link to those of
      other studies both nationally and internationally. Collectively, these studies
      are building up a general picture of the distress, cognitive and emotional
      dissonance experienced by MHNs when using coercive interventions. The findings
      will help to develop MHN education and enhance practice.

PMID- 25944484
TI  - Combined BRAF and MEK inhibition for the treatment of BRAF-mutated metastatic
      melanoma.
AB  - Combined BRAF and MEK inhibition out-performed BRAF inhibitor monotherapy in 3
      randomized Phase 3 studies for BRAF-mutated metastatic melanoma patients and the
      combination of BRAF inhibitor dabrafenib with MEK inhibitor trametinib is now an
      FDA-approved treatment in this setting. Nevertheless, the majority of patients
      face progressive disease even when treated with the combination. Mechanisms of
      resistance to BRAF inhibition have been extensively investigated, whilst less is
      known about the specific mechanisms of resistance to combined therapy. The aim of
      this paper is to review the efficacy and safety of the combination of BRAF plus
      MEK inhibitors compared with BRAF inhibitor monotherapy and immunotherapy, as
      well as to discuss the existing evidence for the mechanisms of resistance to
      combined therapy and assess future treatment strategies to improve outcome based
      on data provided by clinical and translational research studies. 

PMID- 25944482
TI  - The cellular environment regulates in situ kinetics of T-cell receptor
      interaction with peptide major histocompatibility complex.
AB  - T cells recognize antigens at the two-dimensional (2D) interface with antigen
      presenting cells (APCs), which trigger T-cell effector functions. T-cell
      functional outcomes correlate with 2D kinetics of membrane-embedded T-cell
      receptors (TCRs) binding to surface-tethered peptide-major histocompatibility
      complex molecules (pMHCs). However, most studies have measured TCR-pMHC kinetics
      for recombinant TCRs in 3D by surface plasmon resonance, which differs
      drastically from 2D measurements. Here, we compared pMHC dissociation from native
      TCR on the T-cell surface to recombinant TCR immobilized on glass surface or in
      solution. Force on TCR-pMHC bonds regulated their lifetimes differently for
      native than recombinant TCRs. Perturbing the cellular environment suppressed 2D
      on-rates but had no effect on 2D off-rate regardless of whether force was
      applied. In contrast, for the TCR interacting with its monoclonal antibody, the
      2D on-rate was insensitive to cellular perturbations and the force-dependent off
      rates were indistinguishable for native and recombinant TCRs. These data present
      novel features of TCR-pMHC kinetics that are regulated by the cellular
      environment, underscoring the limitations of 3D kinetics in predicting T-cell
      functions and calling for further elucidation of the underlying molecular and
      cellular mechanisms that regulate 2D kinetics in physiological settings.

PMID- 25944485
TI  - Is androgen receptor targeting an emerging treatment strategy for triple negative
      breast cancer?
AB  - Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype. The
      absence of expression and/or amplification of estrogen and progesterone receptor
      as well as ERBB-2 prevent the use of currently available endocrine options and/or
      ERBB-2-directed drugs and indicates chemotherapy as the main current therapy.
      TNBC represents approximately 15% of breast cancer cases with high index of
      heterogeneity. Here, we review the role of androgen receptor in breast
      carcinogenesis and its association with alterations in the expression pattern and
      functional roles of regulatory molecules and signal transduction pathways in
      TNBC. Additionally, based on the so far preclinical and clinical published data,
      we evaluate the perspectives for using and/or developing androgen receptor
      targeting strategies for specific TNBC subtypes. 

PMID- 25944486
TI  - Silibinin and STAT3: A natural way of targeting transcription factors for cancer
      therapy.
AB  - Signal transducer and activator of transcription 3 (STAT3) is constitutively
      activated in many different types of cancer and plays a pivotal role in tumor
      growth and metastasis. Retrospective studies have established that STAT3
      expression or phospho-STAT3 (pSTAT3 or activated STAT3) are poor prognostic
      markers for breast, colon, prostate and non-small cell lung cancer. Silibinin or
      silybin is a natural polyphenolic flavonoid which is present in seed extracts of
      milk thistle (Silybum marianum). Silibinin has been shown to inhibit multiple
      cancer cell signaling pathways in preclinical models, demonstrating promising
      anticancer effects in vitro and in vivo. This review summarizes evidence
      suggesting that silibinin can inhibit pSTAT3 in preclinical cancer models. We
      also discuss current strategies to overcome the limitations of oral
      administration of silibinin to cancer patients to translate the bench results to
      the bed side. Finally, we review the ongoing clinical trials exploring the role
      of silibinin in cancer. 

PMID- 25944487
TI  - Pulmonary regurgitant volume is superior to fraction using background-corrected
      phase contrast MRI in determining the severity of regurgitation in repaired
      tetralogy of Fallot.
AB  - In the assessment of pulmonary regurgitation (PR) using phase contrast MRI, phase
      offset errors affect the accuracy of flow. This study evaluated the use of
      automated background correction for phase offset in the quantification of PR
      fraction and volume in patients with repaired tetralogy of Fallot (TOF), and to
      assess its clinical impact. We retrospectively analyzed 203 cardiac MRI studies,
      performed on 1.5-T scanner. Pulmonary flow (Q(P)) and systemic flow (Q(S)) was
      assessed both with and without background correction. Non-corrected and corrected
      Q(P) was correlated with Q(S). PR was correlated with (1) indexed right
      ventricular end-diastolic volume (RVEDVi) and (2) with differential right and
      left ventricular stroke volumes (PR(SV)). Both PR fraction and volume showed
      major change after correction (-43 to +36% and -13 to +13 ml/m(2)). Corrected
      Q(P) and Q(S) were stronger correlated with each other than non-corrected Q(P)
      and Q(S) [r = 0.78 vs. 0.73 (p < 0.001)]. Both PR fraction and volume were
      stronger correlated with RVEDVi, compared to their non-corrected counterparts (p
      < 0.001). PR volume was stronger correlated with RVEDVi, compared to PR fraction
      [r = 0.74 vs. 0.69 (p < 0.001)]. When patients were divided according to PR
      severity, 12% of patients reclassified after correction. Background correction
      for phase offset significantly changed the quantification of PR. Non-corrected
      assessment of PR may result in the misclassification of patients. Our data
      suggest that the use of PR volume is favourable in the follow-up of patients with
      repaired TOF.

PMID- 25944488
TI  - Excessive Access Cannulation Site Bleeding Predicts Long-Term All-Cause Mortality
      in Chronic Hemodialysis Patients.
AB  - Our group has previously reported that excessive vascular access bleeding during
      dialysis treatment in stable hemodialysis (HD) patients was associated with
      anemia and may indicate poorer health. The association between excessive blood
      loss from access cannulation site and clinical outcomes was unknown. We
      hypothesized that excessive access bleeding may have an impact on all-cause and
      cardiovascular (CV) mortality in this population. We prospectively conducted an
      observational, longitudinal study of 360 HD patients. Excessive access bleeding
      was defined as at least an occurrence of blood loss greater than 4 mL per HD
      session during a study period of one month. During a median follow-up of 83
      months, all-cause mortality and CV mortality were registered. Outcomes were
      analyzed by Kaplan-Meier and Cox proportional hazards regression analyses. A
      total of 118 (32.8%) participants died and 54 of these were from CV death. Using
      a multivariate Cox proportional hazards regression, access bleeding was found to
      be an independent predictor of all-cause mortality (HR 1.67, 95% CI 0.96-2.91, P
      = 0.070) but not for CV death (HR 1.53, 95% CI 0.88-2.68, P = 0.135). Our study
      identified that excessive access cannulation site bleeding could be a novel
      marker for increased risk of death in HD patients. 

PMID- 25944493
TI  - Viral infection: New options to fight Ebola.

PMID- 25944491
TI  - Using dispersants after oil spills: impacts on the composition and activity of
      microbial communities.
AB  - Dispersants are globally and routinely applied as an emergency response to oil
      spills in marine ecosystems with the goal of chemically enhancing the dissolution
      of oil into water, which is assumed to stimulate microbially mediated oil
      biodegradation. However, little is known about how dispersants affect the
      composition of microbial communities or their biodegradation activities. The
      published findings are controversial, probably owing to variations in laboratory
      methods, the selected model organisms and the chemistry of different dispersant
      oil mixtures. Here, we argue that an in-depth assessment of the impacts of
      dispersants on microorganisms is needed to evaluate the planning and use of
      dispersants during future responses to oil spills. 

PMID- 25944495
TI  - High Efficiency Antimicrobial Thiazolium and Triazolium Side-Chain
      Polymethacrylates Obtained by Controlled Alkylation of the Corresponding Azole
      Derivatives.
AB  - Two series of antimicrobial polymethacrylates (PMTAs) bearing mono and bis
      cationic quaternary ammonium cations (QUATs) were prepared by controlled N
      alkylation of 1,3-thiazole and 1,2,3-triazole pendant groups with butyl iodide
      (PMTAs-BuI). The degree of quaternization (DQ) of the azole heterocycles was
      monitored by (1)H NMR spectroscopy over a wide range of reaction times. Spectra
      analysis of the (1)H NMR aromatic region allowed to characterize and quantify the
      different species involved and, therefore, to control the chemical composition
      distribution of the amphiphilic polycations. The polymer charge density and the
      hydrodynamic sizes were measured by zeta potential and dynamic light scattering
      (DLS), respectively. Consequently, the relationship between structure and
      antibacterial properties and toxicity was studied. Interestingly, these
      polyelectrolytes present excellent selective toxicity against bacteria being
      nonhemolytic even at low values of DQ. Furthermore, they were also evaluated for
      their microbial time-killing efficiency, presenting a 3 log-reduction in only 15
      min. Additionally, the bacteria cell morphology treated with PMTAs-BuI was
      analyzed. 

PMID- 25944489
TI  - The interplay between nucleoid organization and transcription in archaeal
      genomes.
AB  - The archaeal genome is organized by either eukaryotic-like histone proteins or
      bacterial-like nucleoid-associated proteins. Recent studies have revealed novel
      insights into chromatin dynamics and their effect on gene expression in archaeal
      model organisms. In this Progress article, we discuss the interplay between
      chromatin proteins, such as histones and Alba, and components of the basal
      transcription machinery, as well as between chromatin structure and gene-specific
      transcription factors in archaea. Such an interplay suggests that chromatin might
      have a role in regulating gene expression on both a global and a gene-specific
      level. Moreover, several archaeal transcription factors combine a global gene
      regulatory role with an architectural role, thus contributing to chromatin
      organization and compaction, as well as gene expression. We describe the emerging
      principles underlying how these factors cooperate in nucleoid structuring and
      gene regulation. 

PMID- 25944496
TI  - Assessment of radiological vertebral fractures in HIV-infected patients: clinical
      implications and predictive factors.
AB  - OBJECTIVES: The aim of this study was to evaluate the clinical impact of
      including lateral spine X-ray in the screening of bone diseases in HIV-positive
      patients. METHODS: A total of 194 HIV-positive patients underwent dual-energy X
      ray absorptiometry (DEXA), lateral spine X-ray and bone biochemical analysis.
      Vertebral fractures were identified using a morphometric analysis of X-rays and
      classified using the semiquantitative scoring system of Genant et al. For each
      patient, a spine deformity index (SDI) score was calculated by summing the grades
      of vertebral deformities. Reductions in vertebral body height of > 25% were
      considered vertebral fractures, and those < 25% were considered vertebral
      deformities. Risk factors associated with vertebral fractures were evaluated by
      univariate and multivariate analysis. RESULTS: Vertebral fractures were detected
      in 24 patients (12.4%) and vertebral deformities in 17 patients (8.7%); 153
      patients (78.9%) did not show any vertebral deformity. Among patients with
      fractures, only two with SDI > 10 reported lumbar pain; the remaining were
      asymptomatic. Patients over 50 years old showed a higher prevalence of vertebral
      fracture [24.4% versus 11.8% in patients 41-50 years old (P = 0.05) and 1.9% in
      patients <= 40 years old (P = 0.04)]. No significant increase in the prevalence
      according to bone mineral density (BMD) reduction was observed, and 70% of
      fractures were diagnosed in nonosteoporotic patients. Older age [adjusted odds
      ratio 1.09; 95% confidence interval (CI) 1.03-1.13; P = 0.001] and steroid use
      (adjusted odds ratio 3.64; 95% CI 1.29-10.3; P = 0.01) were independently
      associated with vertebral fracture; no association was found with HIV- or highly
      active antiretroviral therapy (HAART)-related variables. CONCLUSIONS: A
      prevalence of vertebral fractures of 12.4% was observed in our HIV-positive
      cohort. Given that two-thirds of fractures occurred in nonosteoporotic patients,
      spine X-ray may be considered in patients at increased risk, irrespective of BMD;
      that is, in elderly patients and/or patients using steroids.

PMID- 25944497
TI  - Progress in understanding the diagnosis and molecular genetics of
      macrothrombocytopenias.
AB  - The inherited macrothrombocytopenias constitute a subgroup of congenital platelet
      disorders that is the best characterized from the genetic point of view. This
      clinically heterogeneous subgroup is characterized by a variable degree of
      bleeding but without predisposition to haematological malignancies, as seen in
      the two other subgroups. The classification of inherited thrombocytopenia is
      traditionally based on the description of different clinical and biological
      features, in particular the measurement of the mean platelet volume. In certain
      disorders, biochemical platelet components are abnormal, and their analyses are
      useful in diagnosis. However, these approaches present several limitations, and
      many cases remain undiagnosed, especially for patients without a clear family
      history. An analysis of genetic abnormalities was subsequently used for
      classification, demonstrating that some different clinical entities were, in
      fact, identical. The genomic approach that was used initially to accurately link
      some phenotypic diagnoses with the causal genetic alteration was positional
      cloning and DNA sequencing. More recently, next generation sequencing in the form
      of whole-genome or -exome sequencing and RNA sequencing has been developed. This
      review will focus on the progress in understanding the different
      macrothrombocytopenias that have been identified. 

PMID- 25944498
TI  - Development of Aa New Time Temperature Indicator for Enzymatic Validation of
      Pasteurization of Meat Products.
AB  - This paper presents the development of a new smart time-temperature indicator
      (TTI) of pasteurization whose operating principle is based on the complexation
      reaction between starch and iodine, and the subsequent action of an amylase on
      this complex causing its discoloration at a rate dependent on time and
      temperature of the medium. Laboratory simulations and tests in a manufacturing
      plant evaluated different enzyme concentrations in the TTI prototypes when
      exposed to pasteurization conditions. The results showed that the color response
      of the indicators was visually interpreted as adaptive to measurement using
      appropriate equipment, with satisfactory reliability in all conditions studied.
      The TTI containing 6.5% amylase was one whose best results were suited for use in
      validating the cooking of hams. When attached to the primary packaging of the
      product, this TTI indicated the pasteurization process inexpensively, easily,
      accurately, and nondestructively. 

PMID- 25944499
TI  - Nonsignificant associations between measures of inhibitory control and walking
      while thinking in persons with multiple sclerosis.
AB  - OBJECTIVE: To examine whether inhibitory control measures were associated with
      the dual-task cost (DTC) of walking in persons with multiple sclerosis (MS) and
      matched controls without MS. DESIGN: Cross-sectional study. SETTING: University
      research laboratory. PARTICIPANTS: The sample (N=56) included ambulatory persons
      with relapsing-remitting MS (n=28 [26 women, 2 men]; median Expanded Disability
      Status Scale score, 3.0) from the local community and controls (n=28) matched by
      age, sex, body mass index, and education. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: All participants underwent a modified flanker task followed by
      4 trials of the timed 25-foot walk. The first 2 trials involved walking as
      quickly as possible only (single-task condition), and the second 2 trials
      involved walking as quickly as possible while naming alternate letters of the
      alphabet (dual-task condition). Walking speed under single- and dual-task
      conditions was used to compute a DTC of walking. RESULTS: Persons with MS
      demonstrated a similar DTC of walking compared with matched controls, but
      performed more poorly on inhibitory control measures. Interestingly, inhibitory
      control measures were not associated with DTC of walking in the MS sample (all
      |rho|<.26, P>.19), but were associated with DTC of walking in controls (all
      |rho|>.42, P<.03). CONCLUSIONS: Inhibitory control based on modified flanker
      performance might not be associated with DTC of walking in persons with MS.

PMID- 25944500
TI  - Past and current use of walking measures for children with spina bifida: a
      systematic review.
AB  - OBJECTIVES: To describe walking measurement in children with spina bifida and to
      identify patterns in the use of walking measures in this population. DATA
      SOURCES: Seven medical databases-Medline, PubMed, Embase, Scopus, Web of Science,
      CINAHL, and AMED-were searched from the earliest known record until March 11,
      2014. Search terms encompassed 3 themes: (1) children; (2) spina bifida; and (3)
      walking. STUDY SELECTION: Articles were included if participants were children
      with spina bifida aged 1 to 17 years and if walking was measured. Articles were
      excluded if the assessment was restricted to kinematic, kinetic, or
      electromyographic analysis of walking. A total of 1751 abstracts were screened by
      2 authors independently, and 109 articles were included in this review. DATA
      EXTRACTION: Data were extracted using standardized forms. Extracted data included
      study and participant characteristics and details about the walking measures
      used, including psychometric properties. Two authors evaluated the methodological
      quality of articles using a previously published framework that considers
      sampling method, study design, and psychometric properties of the measures used.
      DATA SYNTHESIS: Nineteen walking measures were identified. Ordinal-level rating
      scales (eg, Hoffer Functional Ambulation Scale) were most commonly used (57% of
      articles), followed by ratio-level, spatiotemporal measures, such as walking
      speed (18% of articles). Walking was measured for various reasons relevant to
      multiple health care disciplines. A machine learning analysis was used to
      identify patterns in the use of walking measures. The learned classifier
      predicted whether a spatiotemporal measure was used with 77.1% accuracy. A trend
      to use spatiotemporal measures in older children and those with lumbar and sacral
      spinal lesions was identified. Most articles were prospective studies that used
      samples of convenience and unblinded assessors. Few articles evaluated or
      considered the psychometric properties of the walking measures used. CONCLUSIONS:
      Despite a demonstrated need to measure walking in children with spina bifida, few
      valid, reliable, and responsive measures have been established for this
      population.

PMID- 25944501
TI  - Rehospitalization After Traumatic Brain Injury: A Population-Based Study.
AB  - OBJECTIVE: To examine, from a Canadian population-based perspective, the
      incidence and etiology of long-term hospital utilization among persons living
      with traumatic brain injury (TBI) by age and sex. DESIGN: Retrospective cohort
      study. SETTING: Acute care hospitals. PARTICIPANTS: Index cases of TBI (N=29,269)
      were identified from the Discharge Abstract Database for fiscal years 2002/2003
      through 2009/2010 and were followed-up until 36 months after injury.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Rehospitalization was
      defined as admission to an acute care facility that occurred up to 36 months
      after index injury. Diagnoses associated with subsequent rehospitalization were
      examined by age and sex. RESULTS: Of the patients with TBI, 35.5% (n=10,390) were
      subsequently hospitalized during the 3-year follow-up period. Multivariable
      logistic regression (controlling for index admission hospital) identified men,
      older age, mechanism of injury being a fall, greater injury severity, rural
      residence, greater comorbidity, and psychiatric comorbidity to be significant
      predictors of rehospitalization in a 3-year period postinjury. The most common
      causes for rehospitalization differed by age and sex. CONCLUSIONS:
      Rehospitalization after TBI is common. Factors associated with rehospitalization
      can inform long-term postdischarge planning. Findings also support examining
      causes for rehospitalization by age and sex.

PMID- 25944502
TI  - Patients' estimates of their sleep times: reliability and impact on diagnosis of
      obstructive sleep apnoea.
AB  - BACKGROUND: Home polysomnography (PSG) is an alternative method for diagnosis of
      obstructive sleep apnoea (OSA). Some types 3 and 4 PSG do not monitor sleep and
      so rely on patients' estimation of total sleep time (TST). AIM: To compare
      patients' subjective sleep duration estimation with objective measures in
      patients who underwent type 2 PSG for probable OSA. METHODS: A prospective
      clinical audit of 536 consecutive patients of one of the authors between 2006 and
      2013. A standard questionnaire was completed by the patients the morning after
      the home PSG to record the time of lights being turned off and estimated time of
      sleep onset and offset. PSG was scored based on the guidelines of the American
      Academy of Sleep Medicine. RESULTS: Median estimated sleep latency (SL) was 20
      min compared with 10 min for measured SL (P < 0.0001). There was also a
      significant difference between the estimated and measured sleep offset time
      (median difference = -1 min, P = 0.01). Estimated TST was significantly shorter
      than the measured TST (median difference = -18.5 min, P = 0.002). No factors have
      been identified to affect patients' accuracy of sleep perception. Only 2% of
      patients had a change in their diagnosis of OSA based on calculated apnoea
      hypopnoea index. CONCLUSIONS: Overall estimated TST in the patients with probable
      OSA was significantly shorter than measured with significant individual
      variability. Collectively, inaccurate sleep time estimation had not resulted in
      significant difference in the diagnosis of OSA.

PMID- 25944503
TI  - Participatory role of zinc in structural and functional characterization of
      bioremediase: a unique thermostable microbial silica leaching protein.
AB  - A unique protein, bioremediase (UniProt Knowledgebase Accession No.: P86277),
      isolated from a hot spring bacterium BKH1 (GenBank Accession No.: FJ177512), has
      shown to exhibit silica leaching activity when incorporated to prepare bio
      concrete material. Matrix-assisted laser desorption ionization mass spectrometry
      analysis suggests that bioremediase is 78% homologous to bovine carbonic
      anhydrase II though it does not exhibit carbonic anhydrase-like activity.
      Bioinformatics study is performed for understanding the various physical and
      chemical parameters of the protein which predicts the involvement of zinc
      encircled by three histidine residues (His94, His96 and His119) at the active
      site of the protein. Isothermal titration calorimetric-based thermodynamic study
      on diethyl pyrocarbonate-modified protein recognizes the presence of Zn(2+) in
      the enzyme moiety. Exothermic to endothermic transition as observed during
      titration of the protein with Zn(2+) discloses that there are at least two
      binding sites for zinc within the protein moiety. Addition of Zn(2+) regains the
      activity of EDTA chelated bioremediase confirming the presence of extra binding
      site of Zn(2+) in the protein moiety. Revival of folding pattern of completely
      unfolded urea-treated protein by Zn(2+) explains the participatory role of zinc
      in structural stability of the protein. Restoration of the lambda max in
      intrinsic fluorescence emission study of the urea-treated protein by Zn(2+)
      similarly confirms the involvement of Zn in the refolding of the protein. The
      utility of bioremediase for silica nanoparticles preparation is observed by field
      emission scanning electron microscopy.

PMID- 25944504
TI  - "How did that happen?" Public responses to women with mobility disability during
      pregnancy.
AB  - BACKGROUND: Little is known about current societal attitudes toward women with
      significant mobility disability who are visibly pregnant. OBJECTIVE: To use
      qualitative descriptive analysis methods to examine perceptions of women with
      significant mobility disability about how strangers reacted to their visible
      pregnancies. METHODS: In late 2013, we conducted 2-h telephone interviews with 22
      women with significant mobility difficulties who had delivered babies within the
      prior 10 years. The semi-structured, open-ended interview protocol addressed wide
      ranging pregnancy-related topics, including statements from strangers. Most
      participants were recruited through social networks, coming from 17 states
      nationwide. We used NVivo to sort the texts for content analysis. RESULTS: The
      women's mean (standard deviation) age was 34.8 (5.3) years; most were white, well
      educated, and higher income, although half had Medicaid during their pregnancies;
      and 18 used wheeled mobility aids. Eighteen women described memorable
      interactions with strangers relating to their pregnancies or newborn babies.
      Strangers' statements fell into six categories: (1) curious; (2) intrusively and
      persistently curious; (3) hostile, including concerns that taxpayers would end up
      supporting the mother and child; (4) questioning woman's competence as a
      potential parent; (5) oblivious, not recognizing visible pregnancy or motherhood;
      and (6) positive. Many women reported strangers asking how their pregnancy had
      happened. The women doubted that visibly pregnant women without disabilities
      evoke the same reactions from strangers. CONCLUSIONS: Women with mobility
      disability who are visibly pregnant may perceive reactions from strangers that
      appear intrusive. Planning ahead for handling such encounters could reduce the
      stresses of these interactions.

PMID- 25944505
TI  - The role of sentinel lymph node biopsy in the management of invasive extramammary
      Paget's disease: Multi-center, retrospective study of 151 patients.
AB  - BACKGROUND: Although extramammary Paget's disease (EMPD) mostly presents as
      intraepithelial carcinoma, we sometimes encounter patients with invasive EMPD
      (iEMPD) who have lymph node metastasis and may develop distant metastasis.
      Although sentinel lymph node biopsy (SLNB) is widely accepted for various
      cancers, there is no large study that has assessed its role in iEMPD. OBJECTIVE:
      The main objective of this study is to assess the role of SLNB in patients with
      iEMPD. MATERIALS AND METHODS: We retrospectively collected data on 151 iEMPD
      patients treated from 1998 to 2012 in 11 institutes in Japan. All 151 patients
      received curative surgery for their primary tumor and none of them had distant
      metastasis. SLNB was performed on the 107 patients without lymphadenopathy to
      determine their LN status. The 44 other patients with lymphadenopathy underwent
      one of the following procedures to determine their LN status: SLNB in 22 cases,
      immediate LN dissection in 21, and LN biopsy in 1. RESULTS: Compared to those
      without lymphadenopathy, patients with lymphadenopathy had advanced primary
      tumors (nodule in the primary tumor, thicker tumor, deeper invasion level, and
      lymphovascular invasion). The rate of LN metastasis in patients with
      lymphadenopathy was 80%, compared to 15% in patients without lymphadenopathy who
      underwent SLNB. Compared to those with negative SLN, patients with positive SLN
      had advanced primary tumors (nodule in the primary tumor, deeper invasion level,
      and lymphovascular invasion). Multivariate analysis revealed that dermal invasion
      (odds ratio 5.8, p=0.04) and lymphovascular invasion (odds ratio 18.0, p=0.0023)
      were independent factors associated with SLN positivity. Notably, there was no
      difference in survival between patients with or without SLN metastasis (p=0.71).
      On the other hand, patients with lymphadenopathy showed worse survival than those
      with positive SLN (p=0.045). CONCLUSION: Clinical lymphadenopathy was strongly
      correlated with pathological LN metastasis and also associated with worse
      survival than absence of lymphadenopathy. The rate of occult LN metastasis
      detected by SLNB was 15%. Survival was not affected by SLN status even when an
      advanced primary tumor was present in patients with positive SLN. Our results
      raise the possibility that SLNB and subsequent LN dissection improved the
      survival of patients with early stage lymphatic spread. Our study indicates that
      SLNB should be considered for iEMPD if lymphadenopathy is not apparent.

PMID- 25944507
TI  - O2, anybody?

PMID- 25944506
TI  - Redescription and Phylogenetic Position of Condylostoma arenarium Spiegel, 1926
      (Ciliophora, Heterotrichea) from Guanabara Bay, Brazil.
AB  - Details on Condylostoma arenarium infraciliature have not been described;
      therefore, it is considered a poorly known species. The lack of detailed
      description on C. arenarium morphology caused several misidentifications that
      have accumulated in the literature. In this study, we present the first complete
      description of C. arenarium infraciliature based on protargol-impregnated
      organisms and scanning electron microscopy. We also have inferred the
      phylogenetic position of this species based on 18S rRNA sequences. The main
      characteristics of C. arenarium population from Guanabara Bay are as follows: in
      vivo elongated body shape with 350-600 MUm length * 70-220 MUm width, they are
      highly contractile when subjected to disturbances, green-yellowish cortical
      granules are present, contractile vacuoles absent, V-shaped peristome comprises
      approximately 1/5 of the total length, adoral zone with 83-145 membranelles, 1-2
      small frontal cirrus observed only in impregnated specimens, 10-15 fiber-like
      stripes arranged transversely on the inner wall of the oral cavity, 30-45 somatic
      kineties, moniliform macronucleus with 15-20 nodules. Some observations on
      morphogenesis of C. arenarium were also included. In phylogenetic analyses, C.
      arenarium clustered with Condylostoma sp. within a clade composed of three C.
      curva sequences with high support values.

PMID- 25944508
TI  - Cardiorespiratory interaction: a novel mechanical approach to treating
      intraoperative hypotension.

PMID- 25944510
TI  - Effects of various factors on sleep disorders and quality of life in Parkinson's
      disease.
AB  - In Parkinson's disease (PD), sleep disorders (SD) occur as a result of the
      neurochemical changes in sleep centres, neurodegenerative changes in dopaminergic
      neurons, and other factors. The most common SD include excessive daytime
      sleepiness, insomnia, restless legs syndrome and nocturia. The aim of the study
      was to compare quality of sleep, as a factor that greatly impacts quality of life
      (QoL), between PD patients and a control group and to further examine SD in the
      PD group with focus on incidence and SD types as well as on effects various
      factors (age, sex, PD characteristics, medication usage) have on these disorders.
      The study included 110 patients who met the criteria for the diagnosis of PD and
      110 age-matched healthy controls. We used the Pittsburgh Sleep Quality Index, PD
      Sleep Scale, Epworth Sleepiness Scale, PD QoL Questionnaire-8 and PD
      Questionnaire-39 (items 30 and 33). In the group with PD, we considered the
      duration of the disease, the stage of disease according to the Hoehn and Yahr
      scale, medications and their impact on the SD. The average duration of the
      disease was 6 years and the mean stage was 2.44. The result showed significant
      differences in the sleep quality between groups. In the PD group, SD differences
      were also found according to gender, duration of the disease and medication
      usage. The most common SD were fragmented sleep, insomnia and nocturia. To
      improve the QoL of PD patients, it is necessary to pay more attention to
      detecting and solving SD. 

PMID- 25944509
TI  - Spying on small wildlife sounds using affordable collar-mounted miniature
      microphones: an innovative method to record individual daylong vocalisations in
      chipmunks.
AB  - Technological advances can greatly benefit the scientific community by making new
      areas of research accessible. The study of animal vocal communication, in
      particular, can gain new insights and knowledge from technological improvements
      in recording equipment. Our comprehension of the acoustic signals emitted by
      animals would be greatly improved if we could continuously track the daily
      natural emissions of individuals in the wild, especially in the context of
      integrating individual variation into evolutionary ecology research questions. We
      show here how this can be accomplished using an operational tiny audio recorder
      that can easily be fitted as an on-board acoustic data-logger on small free
      ranging animals. The high-quality 24 h acoustic recording logged on the spy
      microphone device allowed us to very efficiently collect daylong chipmunk
      vocalisations, giving us much more detailed data than the classical use of a
      directional microphone over an entire field season. The recordings also allowed
      us to monitor individual activity patterns and record incredibly long resting
      heart rates, and to identify self-scratching events and even whining from pre
      emerging pups in their maternal burrow. 

PMID- 25944511
TI  - Longitudinally extensive transverse myelitis in neuromyelitis optica: a
      prospective study of 13 Caucasian patients and literature review.
AB  - Neuromyelitis optica (NMO) is a homogenous disease that can be diagnosed by an
      association of clinical, neuroimaging and serological aspects. We analysed our 4
      years NMO series with longitudinally extensive transverse myelitis (LETM) during
      the disease course. We included consecutive adult Caucasian patients who were
      diagnosed with definite NMO, or cases of NMO-IgG seropositive LETM considered as
      limited forms of NMO. Patients included were negative for other diseases
      (autoimmune, infectious, etc.). We report the Expanded Disability Status Scale
      (EDSS), brain and spine MRI, CSF, NMO-IgG, treatment, motor and visual outcome.
      Thirteen cases fulfilled the inclusion criteria, and the mean follow-up period
      was 3.74 +/- 1.8 years. The initial motor deficit was severe with the mean value
      of motor functional parameter of 4.46 +/- 1 and improved at discharge to 2.53 +/-
      1.4 (p < 0.001). With treatment, the outcome after LETM attack was good in 10
      patients, with a significant improvement of the EDSS mainly upon motor deficit,
      while visual function had a very slight amelioration. The CSF analysis was normal
      in 8 cases; spinal MRI showed evidence of LETM in all patients while brain MRI
      was normal in 7. NMO-IgG is a biomarker for NMO that is of diagnostic value in
      cases of isolated LETM. LETM has a better outcome than ON in NMO Caucasians.
      Spinal MRI is essential for NMO diagnosis in the presence of LETM and the absence
      of multiple brain MRI lesions. Maintenance immunosuppressive therapy reduces the
      frequency of attacks.

PMID- 25944512
TI  - Contrast extravasation mimics cerebral hemorrhage in acute ischemic stroke after
      Solitaire FR clot retrieval and intraarterial thrombolysis: a case report.

PMID- 25944513
TI  - Effect of voluntary hypocapnic hyperventilation on the metabolic response during
      Wingate anaerobic test.
AB  - PURPOSE: We evaluated whether hypocapnia achieved through voluntary
      hyperventilation diminishes the increases in oxygen uptake elicited by short-term
      (e.g., ~30 s) all-out exercise without affecting exercise performance. METHODS:
      Nine subjects performed 30-s Wingate anaerobic tests (WAnT) in control and
      hypocapnia trials on separate days in a counterbalanced manner. During the 20-min
      rest prior to the 30-s WAnT, the subjects in the hypocapnia trial performed
      voluntary hyperventilation (minute ventilation = 31 L min(-1)), while the
      subjects in the control trial continued breathing spontaneously (minute
      ventilation = 14 L min(-1)). RESULTS: The hyperventilation in the hypocapnia
      trial reduced end-tidal CO2 pressure from 34.8 +/- 2.5 mmHg at baseline rest to
      19.3 +/- 1.0 mmHg immediately before the 30-s WAnT. In the control trial, end
      tidal CO2 pressure at baseline rest (35.9 +/- 2.5 mmHg) did not differ from that
      measured immediately before the 30-s WAnT (35.9 +/- 3.3 mmHg). Oxygen uptake
      during the 30-s WAnT was lower in the hypocapnia than the control trial (1.55 +/-
      0.52 vs. 1.95 +/- 0.44 L min(-1)), while the postexercise peak blood lactate
      concentration was higher in the hypocapnia than control trial (10.4 +/- 1.9 vs.
      9.6 +/- 1.9 mmol L(-1)). In contrast, there was no difference in the 5-s peak
      (842 +/- 111 vs. 850 +/- 107 W) or mean (626 +/- 74 vs. 639 +/- 80 W) power
      achieved during the 30-s WAnT between the control and hypocapnia trials.
      CONCLUSIONS: These results suggest that during short-period all-out exercise
      (e.g., 30-s WAnT), hypocapnia induced by voluntary hyperventilation reduces the
      aerobic metabolic rate without affecting exercise performance. This implies a
      compensatory elevation in the anaerobic metabolic rate.

PMID- 25944515
TI  - CD8+ T cell immune response against non-viral pathogens.

PMID- 25944514
TI  - CD8+ T cell immunity in an encephalitis model of Toxoplasma gondii infection.
AB  - Toxoplasma gondii infection induces a robust CD8 T cell immunity in the infected
      host, which is critical for keeping chronic infection under control. IFNgamma
      production and cytolytic activity exhibited by CD8 T cells are critical functions
      needed to prevent the reactivation of latent infection. Paradoxically, the
      susceptible mice infected with the parasite develop encephalitis irrespective of
      the presence of vigorous CD8 T cell immunity. Recent studies from our laboratory
      have demonstrated that these animals have defect in the memory CD8 T cell
      population, which become dysfunctional due to exhibition of inhibitory receptors
      like PD-1. Although the blockade of PD-1-PDL-1 pathway rescues the CD8 response,
      PD-1(hi) expressing cells are refractory to the treatment. In this review, we
      discuss the development of CD8 memory response during chronic infection,
      mechanism responsible for their dysfunctionality, and possible therapeutic
      measures that can be taken to reverse the process. 

PMID- 25944516
TI  - Nomenclature for factors of the HLA system, update March 2015.

PMID- 25944518
TI  - [Postoperative analgesia after total knee arthroplasty: Continuous intra
      articular catheter vs. continuous femoral nerve block].
AB  - BACKGROUND: Postoperative pain management after total knee arthroplasty (TKA)
      remains a great challenge even today. In the context of new fast-track concepts,
      the importance of multimodal therapies for the effective treatment of pain and
      the reduction of side effects, as well as for the rapid ambulation of patients is
      increasing. Therefore, new continuous intra-articular catheter-systems (IAC) are
      under investigation. MATERIALS AND METHODS: A total of 120 patients receiving
      total knee replacement were included in a prospective randomized comparative
      study. In a standardized treatment regime 60 patients received an IAC (group A),
      while in 60 patients a continuous femoral nerve block (FNB) was applied (group
      B). All other perioperative therapy components were identical for all patients.
      In the first 5 days after surgery pain intensity (VAS), passive and active
      flexion, opioid requirements, and self-initiated or hallway ambulation were
      investigated and documented. The initiation time, operation time, and length of
      hospital stay were recorded. RESULTS: Regarding pain intensity no significant
      differences occurred (mean 5.1 +/- 2.5 vs. 4.6 +/- 2.6; p = 0.27). Also,
      additional opioid requirements and range of motion (ROM) showed no relevant
      distinctions of therapy. In the IAC group a much more rapid independent
      mobilization was achieved (p < 0.001). The mean initiation time before surgery
      decreased markedly compared to the FNB group by 11.9 min (p < 0.001). With
      respect to the operation time and duration of hospital stay there was no
      noticeable difference. The failure rate and the rate of dislocation of FNB appear
      to be increased. CONCLUSION: The perioperative treatment with an IAC system is an
      easy technique, which ensures a markedly faster ambulation following TKA compared
      to the treatment with continuous FNB. Hence, its usage, especially in fast-track
      concepts can be recommended. In this study, a comparison of pain intensity, the
      additional requirement of opioids and early range of motion (ROM) offers no
      benefits compared to FNB. Due to time savings cost reduction can be achieved.

PMID- 25944519
TI  - Pharmacokinetics of the first combination 17beta-estradiol/progesterone capsule
      in clinical development for menopausal hormone therapy.
AB  - OBJECTIVE: This study aims to compare the pharmacokinetics and oral
      bioavailability of a capsule combining 17beta-estradiol and progesterone in a non
      peanut oil-containing formulation with those of widely used and approved separate
      formulations of estradiol and progesterone coadministered to healthy
      postmenopausal women. METHODS: This was an open-label, balanced, randomized,
      single-dose, two-treatment, three-period, three-sequence, cross-over, partial
      replicate, reference-scaled study. Postmenopausal women (aged 40-65 y) were
      randomly assigned to one of three dosing sequences of test and reference products
      (TRR, RTR, or RRT, where T is the test drug and R is the coadministered reference
      product), with each of the three periods separated by a 14-day washout. The
      primary pharmacokinetic endpoints were Cmax, AUC(0-t), and AUC(0-inf) for the
      test and reference products, assessed for bioequivalence using the scaled average
      bioequivalence or unscaled average bioequivalence method. Safety was assessed by
      clinical observation, participant-reported adverse events, and laboratory data,
      including blood levels of hormones. RESULTS: Sixty-six women were randomly
      assigned, and 62 women (94.0%) completed all three study periods. All AUC and
      Cmax parameters met bioequivalence criteria for all analytes (estradiol,
      progesterone, and estrone), except Cmax for total estrone. The extent of
      estradiol and progesterone absorption was similar between the test product and
      the reference products. Four adverse events--all considered mild and unrelated to
      the study drugs--were reported. CONCLUSIONS: The combination 17beta
      estradiol/progesterone product demonstrates bioavailability similar to those of
      the respective reference products of estradiol and progesterone. If regulatory
      approval is obtained, this new hormone therapy would be the first treatment of
      menopause symptoms to combine progesterone with 17beta-estradiol in an oral
      formulation.

PMID- 25944517
TI  - [Total ankle replacement in patients with bleeding disorders].
AB  - BACKGROUND: Total ankle replacement (TAR) is a well-accepted treatment option in
      patients with end-stage ankle osteoarthritis. However, published literature on
      patients with bleeding disorders treated with TAR is limited. Therefore, we
      carried out this prospective study to analyze mid-term postoperative results in
      patients with bleeding disorders treated by TAR. METHODS: A total of 34 patients
      with end-stage ankle osteoarthritis--14 patients with hemophilia type A and 20
      patients with von Willebrand disease (VWD)--treated by TAR were included in this
      prospective study. The mean age of patients was 46.0 +/- 9.0 years.
      Intraoperative and postoperative complications were recorded. The postoperative
      pain relief and functional results including range of motion (ROM) and American
      Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score were assessed after a
      mean follow-up of 6.3 +/- 3.4 years. Additionally, the quality of life was
      analyzed using the SF-36 questionnaire. The alignment of prosthesis components
      was assessed using weight-bearing conventional radiographs. The results were
      compared with those obtained in the control group, including 72 and 33 patients
      with post-traumatic and rheumatoid ankle osteoarthritis respectively. RESULTS:
      One patient sustained an intraoperative medial malleolar fracture. In total,
      three revision surgeries were necessary in our patient cohort. There was
      significant pain relief from 8.2 +/- 0.8 to 0.9 +/- 1.0, as assessed using a
      visual analog scale. All categories of the SF-36 score showed significant
      improvement. The average ROM increased from 20.1 degrees  +/- 6.9 degrees  to
      27.5 degrees  +/- 7.4 degrees . The AOFAS hindfoot score increased from 34.5 +/-
      10.0 to 82.4 +/- 10.2 of a maximum of 100 points. Radiographic assessment showed
      the neutral alignment of prosthesis components in all patients. The postoperative
      clinical and radiographic outcomes were comparable in both patients with
      hemophilia and those with VWD. Patients with bleeding disorders had significantly
      higher pain relief and significantly lower ROM than the patients in the control
      group with ankle osteoarthritis of post-traumatic or rheumatoid etiology.
      CONCLUSION: Our prospective study revealed encouraging mid-term outcomes after
      TAR in patients with bleeding disorders. However, this surgery should be limited
      to highly experienced foot and ankle surgeons. Furthermore, this patient cohort
      requires a multidisciplinary approach to ensure a good outcome.

PMID- 25944521
TI  - Prevalence of postmenopausal symptoms in North America and Europe.
AB  - OBJECTIVE: This study aims to evaluate differences and similarities in the
      prevalence of postmenopausal symptoms and their impact on postmenopausal women
      and male partners of postmenopausal women in North America and Europe. METHODS:
      The Internet-based survey Clarifying Vaginal Atrophy's Impact on Sex and
      Relationships (CLOSER) was conducted in North America and Europe. The
      questionnaire included questions on symptoms experienced by women after menopause
      and the impact of these symptoms overall and specifically on emotional and
      physical relationships. This study included 8,200 respondents: 4,100 were
      postmenopausal women who had experienced vaginal discomfort and 4,100 were male
      partners of postmenopausal women with this symptom. Differences were significant
      at the 95% level of confidence. RESULTS: The survey identified vaginal dryness,
      hot flashes, night sweats, disrupted sleep, and weight gain as the top five
      symptoms experienced by postmenopausal women in North America and Europe.
      Overall, symptoms were found to be more prevalent in women from the United
      States, United Kingdom, and Canada (P < 0.05), and less prevalent in women from
      Sweden and Italy compared with other countries. In regards to the impact of
      symptoms overall and on emotional and physical relationships, the greatest number
      of women from the United States, United Kingdom, and Canada found the impact to
      be "worse than expected." CONCLUSIONS: The impact of postmenopausal symptoms on
      relationships is greater in women from countries where symptoms are more
      prevalent. Postmenopausal women and male partners of postmenopausal women may
      benefit from greater education about menopause and open discussions with their
      healthcare provider.

PMID- 25944520
TI  - Confirmatory factor analysis of the Pittsburgh Sleep Quality Index in women with
      hot flashes.
AB  - OBJECTIVE: Women, especially those with hot flashes, report poor sleep quality
      during various stages of the menopausal transition and postmenopause. Sleep
      measurements vary widely because of the copious instruments available. The
      Pittsburgh Sleep Quality Index (PSQI) is a frequently used questionnaire that
      produces a single score for sleep quality. This one-factor structure has not
      received consistent support in the literature. The goal of this analysis was to
      determine the best factor structure of the PSQI in women with hot flashes.
      METHODS: A confirmatory factor analysis was conducted on PSQI baseline data from
      three randomized controlled clinical trials enrolling perimenopausal and
      postmenopausal women with hot flashes (N = 849) from the Menopause Strategies:
      Finding Lasting Answers for Symptoms and Health network. Several a priori factor
      models were compared. RESULTS: One-factor and two-factor models did not fit the
      data. A three-factor model comprising sleep efficiency, perceived sleep quality,
      and daily disturbance showed good fit; however, the sleep medication item was
      dropped because of poor fit and low rates of sleep medication use. The three
      factor model was examined in African-American and white subsamples and was found
      to be similar in both groups; however, two items showed small group differences
      in strength as indicators. CONCLUSIONS: Sleep quality in midlife women with hot
      flashes, as measured by the PSQI, seems to comprise three correlated factors.
      Minor measurement differences detected between groups are of research interest
      but do not necessitate different scoring practices. Additional research is needed
      to further define sleep quality and its associations with health-related
      outcomes.

PMID- 25944522
TI  - One-year treatment persistence with local estrogen therapy in postmenopausal
      women diagnosed as having vaginal atrophy.
AB  - OBJECTIVE: Estrogen therapy is considered to be the most effective treatment of
      vaginal atrophy (VA) symptoms. This retrospective study compares rates of
      pharmacy refill-based treatment persistence in women treated for VA with local
      estrogen therapy (LET) creams versus low-dose vaginally administered tablets.
      METHODS: Study cohort included treatment-naive women aged 45 years or older
      within the IMS PharMetrics Plus claims database who filled one or more
      prescriptions for a LET cream or tablet between January 1, 2010 and September 30,
      2012. Index LET was the first observed LET claim in pharmacy records. Persistence
      was defined as the number of consecutive days of treatment available of the index
      LET during the 12-month follow-up period. In adjusted analyses, we compared the
      risks of discontinuation of index therapy. RESULTS: Of 30,197 women eligible for
      analysis, 12,187 (40.4%) initiated treatment with conjugated estrogens vaginal
      cream, 11,574 (38.3%) initiated treatment with estradiol vaginal cream, and 6,436
      (21.3%) initiated treatment with 10-MUg vaginal estradiol tablets (formulation
      introduced in 2010). Cohorts were comparable on age, geography, and baseline
      comorbidities. During the 12-month follow-up period, 86.2% to 89.4% of cream
      users discontinued LET after the first prescription compared with 57.8% of tablet
      users (P < 0.0001). A greater proportion of tablet initiators than cream users
      were fully (100%) persistent during the 12-month follow-up period. Mean treatment
      duration was 103.4 days for tablets versus 44.6 to 48.1 days for creams (P <
      0.0001). After adjustment for baseline characteristics, tablet initiators had a
      lower risk of discontinuation compared with cream users (P < 0.0001).
      CONCLUSIONS: Low-dose LET tablets, compared with cream formulations, are
      associated with greater persistence in the treatment of VA.

PMID- 25944523
TI  - Indirect comparison of teriparatide, denosumab, and oral bisphosphonates for the
      prevention of vertebral and nonvertebral fractures in postmenopausal women with
      osteoporosis.
AB  - OBJECTIVE: This study aims to compare the efficacy of teriparatide, denosumab,
      and oral bisphosphonates for reducing fracture risk in postmenopausal women with
      osteoporosis. METHODS: We searched the literature, via PubMed, Medline, Embase,
      and the Cochrane Library, to screen citations from January 1996 to October 2014
      for inclusion in this study. A mixed-treatment comparison meta-analysis within a
      Bayesian framework was performed by WinBUGS version 1.4.3 software. The
      proportions of women with vertebral fractures and women with nonvertebral
      fractures were analyzed. RESULTS: Our meta-analysis results indicated that all of
      the therapies-except etidronate-achieved a statistically significant reduction of
      fractures compared with placebo. Teriparatide and denosumab were more effective
      than alendronate and risedronate for reducing vertebral fracture (teriparatide vs
      alendronate: odds ratio [OR], 1.76; 95% CI, 1.03-2.98; teriparatide vs
      risedronate: OR, 1.92; 95% CI, 1.13-3.19; denosumab vs alendronate: OR, 1.67; 95%
      CI, 1.06-2.67; denosumab vs risedronate: OR, 1.84; 95% CI, 1.16-2.92).
      Teriparatide, denosumab, alendronate, and risedronate also reduced the risk of
      nonvertebral fracture compared with placebo. Results of subgroup analysis showed
      that denosumab (OR, 0.6; 95% CI, 0.37-0.98), alendronate (OR, 0.61; 95% CI, 0.39
      0.96), and risedronate (OR, 0.63; 95% CI, 0.46-0.86) can reduce the risk of hip
      fracture and that risedronate (OR, 0.59; 95% CI, 0.4-0.88) can also reduce the
      risk of upper-arm fracture. CONCLUSIONS: Teriparatide, denosumab, alendronate,
      and risedronate are effective in reducing the risk of vertebral and nonvertebral
      fractures in postmenopausal women with osteoporosis. Furthermore, denosumab,
      alendronate, and risedronate can reduce the risk of hip fracture, and risedronate
      can also reduce the risk of upper-arm fracture.

PMID- 25944524
TI  - Serological Follow-up of Tuberculosis in a Wild Boar Population in Contact with
      Infected Cattle.
AB  - There is an increasing concern in several European countries over the role that
      tuberculosis (TB)-infected wild boar may play in the progress of bovine TB
      eradication campaigns. In 2004, as a consequence of the detection of a TB focus
      in wild boar from a National Game Reserve (NGR) located in southern Catalonia, a
      surveillance programme based on post-mortem inspection for detection of
      macroscopic TB-like lesions (TBLL) was initiated in the affected area. The source
      of infection for wild boar was linked to a tuberculous cattle herd located in the
      same area. Besides, the results of the surveillance programme in wild boar were
      used for the validation of an indirect enzyme-linked immunosorbent assay (ELISA)
      specific for Mycobacterium tuberculosis complex (MTBC) IgG antibodies. Using this
      ELISA, a seven-year serological study of MTBC in wild boar from the NGR was
      conducted in 173 animals (93 adults, 44 juveniles-yearlings and 36 piglets)
      culled between 2004 and 2010. ELISA results and presence of TBLL showed excellent
      agreement for adult and juvenile wild boar (Kappa index = 0.85; 95% CI: 0.76
      0.95). Of the thirty-eight adults, yearlings and juveniles classified as
      positives by the ELISA, 34 (89%) showed TBLL at necropsy. In contrast, none of
      the ELISA-positive wild boar piglets (n = 20) showed TBLL, suggesting the
      detection of early antibody responses to the infection. Overall, this study
      contributes to the knowledge of wild boar humoral responses to MTBC. The results
      also highlight the usefulness of this serological test for wild boar TB
      surveillance.

PMID- 25944525
TI  - Involvement of leucocyte/endothelial cell interactions in anorexia nervosa.
AB  - BACKGROUND: Anorexia nervosa is a common psychiatric disorder in adolescence and
      is related to cardiovascular complications. Our aim was to study the effect of
      anorexia nervosa on metabolic parameters, leucocyte-endothelium interactions,
      adhesion molecules and proinflammatory cytokines. MATERIALS AND METHODS: This
      multicentre, cross-sectional, case-control study employed a population of 24
      anorexic female patients and 36 controls. We evaluated anthropometric and
      metabolic parameters, interactions between leucocytes polymorphonuclear
      neutrophils (PMN) and human umbilical vein endothelial cells (HUVEC),
      proinflammatory cytokines such as tumour necrosis factor alpha (TNF-alpha) and
      interleukin-6 (IL-6) and soluble cellular adhesion molecules (CAMs) including E
      selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion
      molecule-1 (ICAM-1). RESULTS: Anorexia nervosa was related to a decrease in
      weight, body mass index, waist circumference, systolic blood pressure, glucose,
      insulin and HOMA-IR, and an increase in HDL cholesterol. These effects
      disappeared after adjusting for BMI. Anorexia nervosa induced a decrease in PMN
      rolling velocity and an increase in PMN rolling flux and PMN adhesion. Increases
      in IL-6 and TNF-alpha and adhesion molecule VCAM-1 were also observed.
      CONCLUSIONS: This study supports the hypothesis of an association between
      anorexia nervosa, inflammation and the induction of leucocyte-endothelium
      interactions. These findings may explain, in part at least, the increased risk of
      vascular disease among patients with anorexia nervosa.

PMID- 25944526
TI  - Illicit drug use in acute care settings.
AB  - INTRODUCTION AND AIMS: While persons with addiction are often hospitalised,
      hospitals typically employ abstinence-based policies specific to illicit drug
      use. Although illicit drug use is known to occur within hospitals, this problem
      has not been well characterised. Therefore, we sought to investigate the
      prevalence of and factors associated with having ever used drugs in hospital
      among people who use drugs in Vancouver, Canada. DESIGN AND METHODS: Data were
      derived from prospective cohort studies of people who use drugs between December
      2012 and May 2013. Multivariable logistic regression was used to identify
      demographic and behavioural factors associated with having ever used illicit
      drugs in hospital. RESULTS: Among 1028 participants who had experienced >=1
      hospitalisation, 43.9% reported having ever used drugs while hospitalised. In
      multivariable analyses, factors positively associated with having ever used drugs
      in hospital included daily cocaine injection and daily crack non-injection (both
      P < 0.05). Factors negatively associated with the outcome included older age and
      male gender (both P < 0.05). The most common reasons for drug use in hospital
      were 'wanting to use' and 'being in withdrawal'. Drugs were most commonly used in
      patient washrooms. DISCUSSION AND CONCLUSIONS: Our findings demonstrate that an
      abstinence-based approach to drug use in hospitals may be ineffective at
      prohibiting drug consumption. High-risk drug use behaviours arising from ongoing
      drug use may pose risks for further harm and illness. Efforts to minimise the
      harms associated with using drugs in hospital are urgently needed. [Grewal HK, Ti
      L, Hayashi K, Dobrer S, Wood E, Kerr T. Illicit drug use in acute care settings.
      Drug Alcohol Rev 2015;34:499-502].

PMID- 25944527
TI  - Challenging the barriers to accessing surgery in low-resource settings: Lessons
      learned from burns.

PMID- 25944528
TI  - Glioblastoma multiforme: Pathogenesis and treatment.
AB  - Each year, about 5-6 cases out of 100,000 people are diagnosed with primary
      malignant brain tumors, of which about 80% are malignant gliomas (MGs).
      Glioblastoma multiforme (GBM) accounts for more than half of MG cases. They are
      associated with high morbidity and mortality. Despite current multimodality
      treatment efforts including maximal surgical resection if feasible, followed by a
      combination of radiotherapy and/or chemotherapy, the median survival is short:
      only about 15months. A deeper understanding of the pathogenesis of these tumors
      has presented opportunities for newer therapies to evolve and an expectation of
      better control of this disease. Lately, efforts have been made to investigate
      tumor resistance, which results from complex alternate signaling pathways, the
      existence of glioma stem-cells, the influence of the blood-brain barrier as well
      as the expression of 0(6)-methylguanine-DNA methyltransferase. In this paper, we
      review up-to-date information on MGs treatment including current approaches,
      novel drug-delivering strategies, molecular targeted agents and immunomodulative
      treatments, and discuss future treatment perspectives. 

PMID- 25944529
TI  - Somatic mosaicism of a novel IKBKG mutation in a male patient with incontinentia
      pigmenti.
AB  - Incontinentia pigmenti (IP) is an X-linked, dominant genodermatosis usually fatal
      in utero in males. In rare circumstances, survival is possible due to abnormal
      karyotype or somatic mosaicism. In this report, the mechanism and significance of
      loss of detectable mutation in peripheral blood leukocytes of a somatic mosaic
      male is discussed and an alternative approach to achieving molecular diagnosis
      presented. A male patient is reported, who initially presented at 2 days of age
      with a rash and seizure. Clinical assessment and histology of a skin biopsy were
      consistent with a diagnosis of IP. He was subsequently found to have bilateral
      retinal detachments. Screening for the common deletion in IKBKG was negative. A
      novel nonsense variant, c.937C>T (p.Gln313*) in IKBKG was identified at an
      approximate level of 15% in a blood sample taken at 10 days of age, but was
      undetectable in a sample taken at 3 years most likely due to selective apoptosis
      of mutant cells. Samples taken from the patient when he was 5-6 years of age
      identified the mutation at a low level in hair root and urine but not in blood or
      buccal cells. The detection of the mutation in cells derived from all germ layers
      indicates a de novo event at an early stage of embryogenesis. This is the first
      report of a nonsense mutation in a male IP patient.

PMID- 25944530
TI  - Sydoxanthone C and acremolin B produced by deep-sea-derived fungus Aspergillus
      sp. SCSIO Ind09F01.
AB  - A new xanthone named sydoxanthone C (1) and a new alkaloid named acremolin B (2),
      together with 10 known compounds (3-12) were isolated from a deep-sea-derived
      fungus Aspergillus sp. SCSIO Ind09F01. The structures of compounds (1-12) were
      determined by the extensive 1D, 2D-NMR, High resolution mass spectra (HRESIMS)
      data. Compounds 7, 8, 11 and 12 showed significant selective cytotoxicities
      against HeLa, DU145 and U937 cell lines. In addition, compounds 7, 8 and 11 also
      exhibited COX-2 inhibitory activities with the prominent IC50 values of 2.4, 7.1
      and 10.6 MUM, respectively. 

PMID- 25944531
TI  - Induced sclerotium formation exposes new bioactive metabolites from Aspergillus
      sclerotiicarbonarius.
AB  - Sclerotia are known to be fungal survival structures, and induction of sclerotia
      may prompt production of otherwise undiscovered metabolites. Aspergillus
      sclerotiicarbonarius (IBT 28362) was investigated under sclerotium producing
      conditions, which revealed a highly altered metabolic profile. Four new compounds
      were isolated from cultivation under sclerotium formation conditions and their
      structures elucidated using different analytical techniques (HRMS, UV, 1D and 2D
      NMR). This included sclerolizine, an alkylated and oxidized pyrrolizine, the new
      emindole analog emindole SC and two new carbonarins; carbonarins I and J. We have
      identified the three latter as true sclerotial metabolites. All metabolites were
      tested for antifungal and antiinsectan activity, and sclerolizine and carbonarin
      I displayed antifungal activity against Candida albicans, while all four showed
      antiinsectan activity. These results demonstrate induction of sclerotia as an
      alternative way of triggering otherwise silent biosynthetic pathways in
      filamentous fungi for the discovery of novel bioactive secondary metabolites.

PMID- 25944532
TI  - Evaluation of agar dilution and broth microdilution methods to determine the
      disinfectant susceptibility.
AB  - A variety of disinfectants have been widely used in veterinary hygiene, food
      industries and environments, which could induce the development of bacterial
      resistance to disinfectants. The methods used to investigate antimicrobial
      effects of disinfectant vary considerably among studies, making comparisons
      difficult. In this study, agar dilution and broth microdilution methods were used
      to compare the antimicrobial activities of four quaternary ammonium compounds
      (QACs) against foodborne and zoonotic pathogens. The potential relationship
      between the presence of QACs resistance genes and phenotypic resistance to QACs
      was also investigated. Our results indicated that the minimum inhibitory
      concentrations (MICs) determined by two methods might be different depended upon
      different QACs and bacteria applied. Regardless of the testing methods,
      Klebsiella pneumoniae was more tolerant among Gram-negative strains to four QACs,
      followed by Salmonella and Escherichia coli. The agreement between MICs obtained
      by the two methods was good, for benzalkonium chloride (78.15%),
      didecyldimethylammonium chloride (DDAC) (82.35%), cetylpyridinium chloride (CTPC)
      (97.48%) and cetyltrimethylammonium bromide (CTAB) (99.16%), respectively. Among
      all Gram-negative bacteria, 94.55% (n=52) of qacEDelta1-positive strains showed
      higher MICs (512 mg l(-1)) to CTAB. The qacEDelta1 gene was highly associated
      (P<0.05) with the high MICs of QACs (?512 mg l(-1)). In addition, DDAC remained
      as the most effective disinfectant against both Gram-positive and Gram-negative
      bacteria. This is the first study that compared the agar dilution and broth
      microdilution methods to assess the antimicrobial activity of QACs. The study
      demonstrated the need to standardize method that would be used in evaluating QACs
      antimicrobial properties in the future. 

PMID- 25944533
TI  - Dibenzocyclooctadiene lignans from Schisandra spp. selectively inhibit the growth
      of the intracellular bacteria Chlamydia pneumoniae and Chlamydia trachomatis.
AB  - Lignans from Schisandra chinensis berries show various pharmacological
      activities, of which their antioxidative and cytoprotective properties are among
      the most studied ones. Here, the first report on antibacterial properties of six
      dibenzocyclooctadiene lignans found in Schisandra spp. is presented. The activity
      was shown on two related intracellular Gram-negative bacteria Chlamydia
      pneumoniae and Chlamydia trachomatis upon their infection in human epithelial
      cells. All six lignans inhibited C. pneumoniae inclusion formation and infectious
      progeny production. Schisandrin B inhibited C. pneumoniae inclusion formation
      even when administered 8 h post infection, indicating a target that occurs
      relatively late within the infection cycle. Upon infection, lignan-pretreated C.
      pneumoniae elementary bodies had impaired inclusion formation capacity. The
      presence and substitution pattern of methylenedioxy, methoxy and hydroxyl groups
      of the lignans had a profound impact on the antichlamydial activity. In addition
      our data suggest that the antichlamydial activity is not caused only by the
      antioxidative properties of the lignans. None of the compounds showed inhibition
      on seven other bacteria, suggesting a degree of selectivity of the antibacterial
      effect. Taken together, the data presented support a role of the studied lignans
      as interesting antichlamydial lead compounds.

PMID- 25944534
TI  - Ascosteroside C, a new mitochondrial respiration inhibitor discovered by
      pesticidal screening using recombinant Saccharomyces cerevisiae.

PMID- 25944535
TI  - Activity of lipophilic and hydrophilic drugs against dormant and replicating
      Mycobacterium tuberculosis.

PMID- 25944536
TI  - Avellanin C, an inhibitor of quorum-sensing signaling in Staphylococcus aureus,
      from Hamigera ingelheimensis.

PMID- 25944537
TI  - Retinopathy in type 1 diabetes mellitus: Major differences between rural and
      urban dwellers in northwest Ethiopia.
AB  - AIM: To audit levels of diabetes-related eye disease in Type 1 diabetes mellitus
      (T1DM) patients in northwest Ethiopia. In particular to establish whether,
      despite identical clinical goals, major differences between the physically
      demanding life-style of rural subsistence farmers and the sedentary life-style of
      urban dwellers would influence the prevalence of diabetes-related eye
      complications. METHODS: A robust infrastructure for chronic disease management
      that comprehensively includes all rural dwellers was a pre-requisite for the
      investigation. A total of 544 T1DM were examined, representing 80% of all T1DM
      patients under regular review at both the urban and rural clinics and
      representative of patient age and gender (62.1% male, 37.9% female) of T1DM
      patients from this region; all were supervised by the same clinical team. Eye
      examinations were performed for visual acuity, cataract and retinal changes
      (retinal photography). HbA1c levels and the presence or absence of hypertension
      were recorded. RESULTS/CONCLUSIONS: Urban and rural groups had similar
      prevalences of severe visual impairment/blindness (7.0% urban, 5.2% rural) and
      cataract (7.3% urban, 7.1% rural). By contrast, urban dwellers had a
      significantly higher prevalence of retinopathy compared to rural patients, 16.1%
      and 5.0%, respectively (OR 2.9, p<0.02, after adjustment for duration, age,
      gender and hypertension). There was a 3-fold greater prevalence of hypertension
      in urban patients, whereas HbA1c levels were similar in the two groups. Since
      diabetic retinopathy is closely associated with microvascular disease and
      endothelial dysfunction, the possible influences of hypertension to increase and
      of sustained physical activity to reduce endothelial dysfunction are discussed.

PMID- 25944540
TI  - Introduction for the proceedings of Origins 2014.

PMID- 25944538
TI  - Associations of circulating 25(OH)D with cardiometabolic disorders underlying
      type 2 diabetes mellitus in an Aboriginal Canadian community.
AB  - AIMS: To investigate the associations of 25-hydroxyvitamin D (25(OH)D) with
      insulin resistance (IR), beta-cell function and metabolic syndrome (MetS) in a
      First Nations population. METHODS: We conducted a cross-sectional analysis using
      data from the Sandy Lake Health and Diabetes Project (2003-2005). A total of 390
      participants (>12 y) were assessed for 25(OH)D, fasting glucose, insulin, lipids,
      blood pressure, inflammatory markers, anthropometric and lifestyle variables and
      a 75-g oral glucose tolerance test was administered. IR was calculated using the
      Matsuda insulin sensitivity index (ISOGTT) and the computational homeostasis
      model assessment of IR (HOMA2-IR). Beta-cell function was calculated using the
      insulinogenic index (IGI) divided by HOMA-IR (IGI/IR) and the insulin secretion
      sensitivity index-2 (ISSI-2). The 2009 harmonized criteria were used to define
      MetS. RESULTS: Higher 25(OH)D was associated with a decreased prevalence of
      dysglycemia (OR = 0.71 95% CI, 0.51-0.97 per SD increase). In addition, there
      were significant associations of 25(OH)D with measures of insulin action (ISOGTT;
      beta=0.31; 95% CI, 0.12, 0.49; HOMA2-IR; beta = -29; 95% CI -0.46, -0.11 and beta
      cell function (ISSI-2; beta = 0.15; 95% CI, 0.02, 0.28). The prevalence of MetS
      was 41%. There was a decreased risk (OR=0.73, 95% CI 0.56, 0.94) of MetS per SD
      increase in baseline 25(OH)D. Finally, there was a significant positive
      association of 25(OH)D with adiponectin (beta = 0.16; 95% CI = 0.01, 0.31).
      CONCLUSIONS: These results support a potential role for vitamin D metabolism in
      the natural history of T2DM among Aboriginal Canadians, although carefully
      designed randomized trials will be required to establish causality.

PMID- 25944541
TI  - A Critical Review of the Concept of Transgenic Plants: Insights into
      Pharmaceutical Biotechnology and Molecular Farming.
AB  - Using transgenic plants for the production of high-value recombinant proteins for
      industrial and clinical applications has become a promising alternative to using
      conventional bioproduction systems, such as bacteria, yeast, and cultured insect
      and animal cells. This novel system offers several advantages over conventional
      systems in terms of safety, scale, cost-effectiveness, and the ease of
      distribution and storage. Currently, plant systems are being utilised as
      recombinant bio-factories for the expression of various proteins, including
      potential vaccines and pharmaceuticals, through employing several adaptations of
      recombinant processes and utilizing the most suitable tools and strategies. The
      level of protein expression is a critical factor in plant molecular farming, and
      this level fluctuates according to the plant species and the organs involved. The
      production of recombinant native and engineered proteins is a complicated
      procedure that requires an inter- and multi-disciplinary effort involving a wide
      variety of scientific and technological disciplines, ranging from basic
      biotechnology, biochemistry, and cell biology to advanced production systems.
      This review considers important plant resources, affecting factors, and the
      recombinant-protein expression techniques relevant to the plant molecular farming
      process.

PMID- 25944542
TI  - Rice (Oryza sativa L) plantation affects the stability of biochar in paddy soil.
AB  - Conversion of rice straw into biochar for soil amendment appears to be a
      promising method to increase long-term carbon sequestration and reduce greenhouse
      gas (GHG) emissions. The stability of biochar in paddy soil, which is the major
      determining factor of carbon sequestration effect, depends mainly on soil
      properties and plant functions. However, the influence of plants on biochar
      stability in paddy soil remains unclear. In this study, bulk and surface
      characteristics of the biochars incubated without rice plants were compared with
      those incubated with rice plants using a suite of analytical techniques. Results
      showed that although rice plants had no significant influence on the bulk
      characteristics and decomposition rates of the biochar, the surface oxidation of
      biochar particles was enhanced by rice plants. Using (13)C labeling we observed
      that rice plants could significantly increase carbon incorporation from biochar
      into soil microbial biomass. About 0.047% of the carbon in biochar was
      incorporated into the rice plants during the whole rice growing cycle. These
      results inferred that root exudates and transportation of biochar particles into
      rice plants might decrease the stability of biochar in paddy soil. Impact of
      plants should be considered when predicting carbon sequestration potential of
      biochar in soil systems. 

PMID- 25944543
TI  - Rebek imide platforms as model systems for the investigation of weak
      intermolecular interactions.
AB  - A Rebek imide receptor with an acetylene-linked phenyl ring complexes 2,6
      di(isobutyramido)pyridine in (CDCl2 )2 via triple H-bonding and pi-pi-stacking
      interactions, and the influence of para-substituents on both rings was
      investigated by (1) H NMR binding titrations. When the phenyl ring was extended
      to biphenyl and the C(4)-pyridine substituent varied, interaction energies
      increased in the order CH3 CH2 ???phenyl<CH3 S???phenyl<phenyl???phenyl?N
      methylcarboxamide???phenyl, highlighting the energetic gain from pi stacking on
      amide fragments. The predicted preference of amide-pi stacking for an
      antiparallel alignment of the local dipoles could not be confirmed with the
      studied system. Different substituents were introduced in the para position of
      the phenyl ring and their interaction with bound 2,6-di(isobutyramido)pyridine
      was investigated. Theoretical predictions that the mere introduction of a
      substituent has a stabilizing effect on pi-pi stacking, regardless of its
      electronic nature, were experimentally confirmed. 

PMID- 25944544
TI  - Predictors of Outcome in Patients Presenting with Acute Ischemic Stroke and Mild
      Stroke Scale Scores.
AB  - BACKGROUND: Although National Institutes of Health Stroke Scale (NIHSS) is a
      known predictor of outcome in acute ischemic stroke, there are other factors like
      age, ambulatory status, and ability to swallow that may be predictors of outcome
      but are not assessed by the traditional NIHSS. The aim of this retrospective
      review was to identify predictors of outcome in mild ischemic stroke. METHODS:
      Discharge outcomes from patients who presented to our large academic stroke
      center with acute ischemic stroke from 2005 to 2013 were retrospectively
      reviewed. Of 7189 patients reviewed, 2597 had initial NIHSS less than 5. Outcome
      measures were modified Rankin Scale (MRS) score 0-1 and discharge to home.
      RESULTS: In all, 65% of patients with NIHSS 0-4 were discharged directly home
      independent of treatment. Of those patients discharged to home, 74% were able to
      ambulate independently and 98% passed their dysphagia screen. Of patients not
      discharged directly home, 66% were unable to ambulate independently and 21% did
      not pass their dysphagia screen. Multivariate logistic regression analysis
      revealed a significant effect of dysphagia screen (P = .001), ability to ambulate
      independently (P = .002), age (P = .016), and NIHSS (P = .005) on discharge to
      home but not MRS of 0-1 (P = .564). CONCLUSIONS: In patients with mild stroke
      scale scores defined as NIHSS 0-4, several factors including age, NIHSS,
      ambulatory status, and ability to swallow may be independent predictors of
      functional outcome and discharge home. These data support the development of a
      modified grading system for assessing functional outcome in mild stroke that
      considers these factors.

PMID- 25944545
TI  - Bereaved carers' accounts of the end of life and the role of care providers in a
      'good death': A qualitative study.
AB  - BACKGROUND: The way that people die is particularly important to those who are
      left behind and this memory is not limited to the moment of death, but
      encompasses the entire end-of-life phase. While a number of attributes for a
      'good death' have been identified, less is known about how care providers feature
      within these conceptualisations. AIM: The aim of this article is to describe the
      end-of-life experience from the point of view of bereaved family carers with
      particular reference to the role that care providers play in shaping this
      experience. DESIGN: Qualitative interviews carried out as part of a study to
      evaluate a new rapid response hospice at home service. An interpretive thematic
      analysis using the Framework approach was used to examine how family carers judge
      a 'good death' and how care providers feature in the attributes of a 'good
      death'. PARTICIPANTS AND SETTING: A total of 44 interviews with bereaved family
      carers from a hospice population in the South East of England. RESULTS: Six
      themes were identified as attributes of a good death in which care providers had
      a key role: social engagement and connection to identity, care provider
      characteristics and actions, carer's confidence and ability to care, preparation
      and awareness of death, presentation of the patient at death and support after
      death for protected grieving. CONCLUSION: Care providers played a much wider role
      in social aspects of care at the end of life than previously considered.

PMID- 25944546
TI  - Proteome research in urothelial carcinoma.
AB  - In all creatures including humans, the molecules that function in accordance with
      the genetic code are mainly proteins. After completing the sequencing of the
      human genome, rapid progress has been made in proteome analysis. The primary
      structures of almost all proteins were determined by the human genome sequence.
      However, the whole picture of proteins cannot be elucidated because of
      alternative splicing and post-translational modifications. Therefore, genomic as
      well as systematic and comprehensive information of proteins is required. Modern
      methods of proteomics have dramatically improved the quality and speed of protein
      analysis. Developments in both bioinformatics and mass spectrometry have
      contributed to the technical improvement, making it possible to identify proteins
      in a short time with high accuracy even from a very small sample. In the field of
      cancer research, many studies of useful diagnostic and prognostic biomarkers
      using these proteomic technologies have been reported, and target molecules for
      treatment have been explored. The aim of the present review was to summarize the
      basic technologies of proteomics and recent research in the field of urothelial
      cancer obtained using proteomic methods. 

PMID- 25944547
TI  - Margaret McCartney: Bad language.

PMID- 25944548
TI  - An Interview Study on "Providing Structure" as an Intervention in Psychiatric
      Inpatient Care: The Nursing Perspective.
AB  - PURPOSE: To gain insight into nurses' perceptions and use of providing structure
      (PS) as an intervention during psychiatric inpatient care. DESIGN AND METHODS:
      Interviews were conducted with nurses (n = 18) from two inpatient wards in
      psychiatry immediately following the occurrence of a PS event. This was done
      immediately following the occurrence of a PS event. Transcripts were analyzed
      using a qualitative coding process. FINDINGS: Four general and 14 specific PS
      activities were described associated with the nursing intervention PS. PRACTICE
      IMPLICATIONS: Nurses can now refer to specific activities of PS. An elaborated
      definition of PS is provided to facilitate a better understanding and using of PS
      as a psychiatric nursing intervention.

PMID- 25944550
TI  - Zinc Absorption from Fortified Milk Powder in Adolescent Girls.
AB  - Zinc (Zn) is essential for development, growth, and reproduction. The Mexican
      government subsidizes micronutrient-fortified milk for risk groups, with positive
      effect on the targeted groups' plasma Zn level, inferring a good absorption is
      achieved although it has not being measured. The aim of this study was to
      determine the impact of micronutrient-fortified milk intake during 27 days on Zn
      absorption in adolescent girls from northwest Mexico. Therefore, Zn absorption
      was evaluated in 14 healthy adolescent girls (14.1 years old) with adequate
      plasma Zn levels, before and after 27 days of fortified Zn milk intake.
      Fractional Zn absorption (FZA) was calculated from urinary ratios of stable
      isotopic Zn tracers administered orally and intravenously on days 0 and 27, and
      total absorbed Zn (TZA) was calculated. At the beginning, Zn intake was 6.8 +/-
      0.85 mg/d (mean +/- SE), and 50 % of the adolescent girls did not achieve their
      requirement (7.3 mg/d). Additionally, FZA was negatively correlated with Zn
      intake (r =-0.61, p = 0.02), while TZA (1.06 mg/d) was insufficient to cover the
      physiologic requirements of adolescent girls (3.02 mg/d). At the end of the
      intervention, all the girls reached the Zn intake recommendation and TZA, 3.09
      mg/d, which was enough to meet the physiological requirement for 57 % of the
      adolescent girls. Therefore, the low Zn intake and the Zn status of adolescent
      girls were positively impacted by Zn-fortified milk intake and its good
      absorption rate. 

PMID- 25944549
TI  - A retrospective cohort study of cause-specific mortality and incidence of
      hematopoietic malignancies in Chinese benzene-exposed workers.
AB  - Benzene exposure has been causally linked with acute myeloid leukemia (AML), but
      inconsistently associated with other hematopoietic, lymphoproliferative and
      related disorders (HLD) or solid tumors in humans. Many neoplasms have been
      described in experimental animals exposed to benzene. We used Poisson regression
      to estimate adjusted relative risks (RR) and the likelihood ratio statistic to
      derive confidence intervals for cause-specific mortality and HLD incidence in
      73,789 benzene-exposed compared with 34,504 unexposed workers in a retrospective
      cohort study in 12 cities in China. Follow-up and outcome assessment was based on
      factory, medical and other records. Benzene-exposed workers experienced increased
      risks for all-cause mortality (RR = 1.1, 95% CI = 1.1, 1.2) due to excesses of
      all neoplasms (RR = 1.3, 95% CI = 1.2, 1.4), respiratory diseases (RR = 1.7, 95%
      CI = 1.2, 2.3) and diseases of blood forming organs (RR = infinity, 95% CI = 3.4,
      infinity). Lung cancer mortality was significantly elevated (RR = 1.5, 95% CI =
      1.2, 1.9) with similar RRs for males and females, based on three-fold more cases
      than in our previous follow-up. Significantly elevated incidence of all myeloid
      disorders reflected excesses of myelodysplastic syndrome/acute myeloid leukemia
      (RR = 2.7, 95% CI = 1.2, 6.6) and chronic myeloid leukemia (RR = 2.5, 95% CI =
      0.8, 11), and increases of all lymphoid disorders included excesses of non
      Hodgkin lymphoma (RR = 3.9, 95%CI = 1.5, 13) and all lymphoid leukemia (RR = 5.4,
      95%CI = 1.0, 99). The 28-year follow-up of Chinese benzene-exposed workers
      demonstrated increased risks of a broad range of myeloid and lymphoid neoplasms,
      lung cancer, and respiratory diseases and suggested possible associations with
      other malignant and non-malignant disorders.

PMID- 25944551
TI  - Schizophrenia through the carers' eyes: results of a European cross-sectional
      survey.
AB  - Schizophrenia is a serious mental disorder affecting approximately 29 million
      people worldwide. The ideal treatment and care of patients with schizophrenia
      should be provided by a multidisciplinary 'team' involving psychiatrists, nurses
      and other healthcare professionals, together with carers and patients. In light
      of the key role carers play in the care of patients with schizophrenia, the
      present survey was designed to assess the opinions of family members and friends
      of patients with schizophrenia across Europe and to ascertain their attitudes
      towards the illness, medication and adherence to medication. Among carers
      participating in this survey, there was widespread awareness of the issues
      involved in supporting patients with schizophrenia and the importance of their
      role in improving poor adherence to medication. Three differences in opinion
      emerged between the views of carers and psychiatrists; psychiatrists rely more on
      the patient themselves when assessing adherence than carers would recommend; in
      contrast to psychiatrists, many carers believe the illness itself contributes to
      non-adherence; two thirds of carers think that schizophrenia medication damages
      health (higher than estimated by psychiatrists). The findings from the present
      survey, taken together with the results from the Adherencia Terapeutica en la
      Esquizofrenia surveys of psychiatrists and nurses, support the need for a
      collaborative approach to the issue of treatment nonadherence. In particular,
      healthcare professionals should recognize the valuable contribution that family
      carers can make to improve treatment adherence and consequently clinical outcomes
      for patients with schizophrenia. Schizophrenia carries a significant burden for
      families providing care. The Adherencia Terapeutica en la Esquizofrenia (ADHES)
      carers' survey was designed to assess the opinions of family and friends of
      patients with schizophrenia across Europe and ascertain their attitudes towards
      the illness, medication and adherence to medication. A questionnaire-based cross
      sectional survey of 138 carers across 16 European countries. Interpretation of
      results was based on a descriptive comparison of responses. Carers recognized the
      importance of medication to help patients get better (76%) and improve their
      quality of life (76%) and relationships (74%). Sixty-seven per cent believed
      medication damages general health. Sixty-five per cent reported that treatment
      adherence was a burden for patients. Thirty-eight per cent indicated that it was
      a daily struggle to get patients to take their medication. Fifty per cent
      perceived that medication administered every few weeks rather than daily was
      quite/very important. Ninety-three per cent agreed on the importance of family
      support to boost adherence, with education and information deemed important for
      families and patients. Carers rely less on the patient themselves when assessing
      adherence than psychiatrists. The burden faced by carers and patients in taking
      medication provides an opportunity for healthcare professionals to provide
      support in a multidisciplinary 'team' involving psychiatrists, nurses and carers.

PMID- 25944552
TI  - The Dorsal Triangular Fibrocartilage of the Metacarpophalangeal Joint: A
      Cadaveric Study.
AB  - PURPOSE: To describe a fibrocartilaginous structure on the dorsal surface of the
      metacarpophalangeal (MCP) joint. METHODS: A combination of anatomical dissection,
      histology, ultrasound, and magnetic resonance imaging was undertaken to explore
      the anatomical structure described, with clinical correlation undertaken by
      surgical exploration of MCP joints. RESULTS: A dorsal structure of the MCP joint
      was identified as fibrocartilagenous in composition, triangular in shape, and
      together with the volar plate and collateral and accessory collateral ligaments
      forming a deepened dorsal fossa in which the metacarpal head invaginated. It was
      attached to the extensor tendon by loose connective tissue and formed part of the
      joint capsule. CONCLUSIONS: The dorsal fibrocartilage of the MCP joint is a
      constant anatomical structure that appears to complement the structural support
      for the metacarpal head and extensor tendon. Possible functions include
      stabilization of the extensor tendon, formation of a dorsal fossa, prevention of
      extensor tendon attrition, and synovial fluid production. Its structure and
      function may have implications in future development of joint replacement
      devices. CLINICAL RELEVANCE: This study adds to the collective knowledge about
      the precise anatomy of the MCP joint. Reconstructive surgery and, in particular,
      joint replacement surgery should consider the potential function and importance
      of this structure when designing interventions on the joint.

PMID- 25944553
TI  - Risk Assessment of Tendon Attrition Following Treatment of Distal Radius
      Fractures With Volar Locking Plates Using Audible Crepitus and Placement of the
      Plate: A Prospective Clinical Cohort Study.
AB  - PURPOSE: To identify risk factors for tendon attrition after volar locking plate
      fixation of distal radius fractures. METHODS: We prospectively assessed attrition
      of the flexor pollicis longus tendon at volar plate removal in 127 hands in 126
      patients. We also evaluated preoperative lateral wrist radiographs, sonographs,
      and crepitus with flexor pollicis longus tendon motion and compared the
      demographic and radiographic characteristics of patients with and without tendon
      attrition. Multivariate logistic regression analysis was employed to identify the
      factors independently associated with tendon attrition. RESULTS: We found 12
      cases of tendon attrition (10%) and 1 that presented with tendon rupture in our
      cohort. Crepitus was recognized in 14 patients (11%): 6 cases (50%) were among
      the 12 hands in 12 patients with tendon attrition whereas 8 (7%) were detected in
      the remaining 114 hands in 113 patients. Logistic regression examination revealed
      that audible crepitus and volar placement of the plate in lateral radiographs
      were independent predictors of tendon attrition. CONCLUSIONS: Crepitus and volar
      placement of hardware in lateral radiographs were independent risk factors for
      flexor tendon attrition after volar plating for distal radius fracture. These
      results may facilitate surgical decisions regarding early plate removal to
      prevent possible tendon rupture. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic II.

PMID- 25944554
TI  - New strategies to develop new medications for lung cancer and metastasis.
AB  - With the advances in cancer and molecular biology and the rapid progress in
      genomics, significant progress has been made in the treatment of lung cancer in
      the past decade. Targeted therapies have been developed for nonsmall cell lung
      cancer (NSCLC), and significant improvement in survival has been achieved. There
      is still, however, no cure for advanced NSCLC. Resistance to initial therapy is
      universal, and the lethal outcome of metastatic disease still remains. Approaches
      to preventing metastases and overcoming resistance to therapy are necessary to
      ensure long-term survival of patients with advanced lung cancer. 

PMID- 25944555
TI  - Effects of recombinant human prothrombin on thrombin generation in plasma from
      patients with hemophilia A and B.
AB  - BACKGROUND: The present study was carried out to investigate the impact of FII
      levels, and their increase, on the hemostatic potential in plasma from hemophilia
      A and B patients with and without inhibitors. METHOD: Recombinant human factor
      (F) II (rhFII) was added ex vivo to plasma from 68 patients with hemophilia A and
      B, with or without inhibitors. The hemostatic potential as measured by thrombin
      generation (calibrated automated thrombogram [CAT]) was focused on the endogenous
      thrombin potential (ETP) as it has been shown to correlate with the clinical
      phenotype of bleeding in hemophilia patients and has also been used to guide
      bypassing therapy in hemophilia patients with inhibitors before elective surgery.
      The factor eight inhibitor bypassing agent (FEIBA((r)) ) was used as a reference
      to the clinical situation. RESULTS: The study shows that rhFII concentration
      dependently increased ETP by a similar magnitude in hemophilia A and B, both with
      and without inhibitors. Compared with FEIBA, rhFII showed a shallower
      concentration-response curve. In both types of hemophilia 100 mg L(-1) of rhFII
      roughly doubled the ETP. A corresponding response was obtained by 0.5 U mL(-1) of
      FEIBA. CONCLUSION: These data support the theory that FII is one of the major
      components responsible for the efficacy of FEIBA. The data also indicate that
      rhFII may be useful, alone or in combination with other coagulation factors, in
      some of the conditions for which FEIBA is used today, although more data are
      needed to substantiate this.

PMID- 25944556
TI  - Amino acid-derived betaines dominate as urinary markers for rye bran intake in
      mice fed high-fat diet--A nontargeted metabolomics study.
AB  - SCOPE: Bioprocessing of whole grain cereals may affect the bioavailability of
      phytochemicals associated with grain fiber and ultimately lead to different
      health outcomes. Here, we studied the impact of long-term feeding with intact and
      bioprocessed rye bran on the urinary phytochemical profile of mice. METHODS AND
      RESULTS: Nontargeted hydrophilic interaction chromatography-ESI-qTOF-MS
      metabolite profiling approach was applied on urine samples collected from three
      groups of diet-induced obese mice fed for 8 weeks with one of the three diets:
      high-fat (HF) control diet, HF diet enriched with intact rye bran, or HF diet
      enriched with bioprocessed rye bran. The most striking finding was the increased
      urinary excretion of several amino-acid derived betaines after both rye diets.
      These included proline betaine, alanine betaine, valine betaine, phenylalanine
      betaine, pipecolic acid betaine, and trigonelline, but not glycine betaine.
      Furthermore, bioprocessing may have improved the bioavailability of rye-derived
      phytochemicals, as higher increase in, e.g. ferulic acid and benzoxazinoid
      metabolites were observed in urine of mice fed with bioprocessed than intact rye
      bran. CONCLUSION: Urinary excretion of various betaines was greatly increased in
      mice fed rye brans. Furthermore, bioprocessing of rye bran appears to serve as a
      beneficial way to improve the bioavailability of various phytochemicals.

PMID- 25944557
TI  - Impact of Switching From Darbepoetin Alfa to Epoetin Beta Pegol on Iron
      Utilization and Blood Pressure in Peritoneal Dialysis Patients.
AB  - New erythropoiesis-stimulating agents with a longer half-life have been developed
      for the treatment of anemia in patients with end-stage renal disease. This study
      evaluated the efficacy of darbepoetin alfa (DA) and long-acting epoetin beta
      pegol (continuous erythropoietin receptor activator, CERA) in patients on
      peritoneal dialysis (PD). Twenty-nine patients who had undergone PD for at least
      6 months and were iron replacement-naive and negative for inflammatory parameters
      were enrolled. Hemoglobin (Hgb) levels and blood pressure were evaluated before
      and after switching from DA to CERA. Percent transferrin saturation (TSAT), serum
      ferritin levels and blood pressure were also assessed. Twenty-eight patients were
      subject to the analysis, excluding one patient with a decrease in Hgb by >=10%.
      Switching from DA to CERA did not alter Hgb levels. The doses of DA and CERA
      after 12 month treatment of each agent were 118.48 +/- 79.63 and 89.88 +/- 47.50
      MUg/4 weeks, respectively (conversion ratio, 1:0.76). The CERA dose administered
      during the final 6 months was abated, compared with that given during the initial
      6 months (P = 0.035). The frequency of CERA injection over a 12-month period was
      less than that of DA (10.0 +/- 3.0 vs. 16.4 +/- 5.0, P < 0.01). The conversion
      from DA to CERA did not alter TSAT, but decreased serum ferritin levels (from
      202.69 +/- 132.57 to 150.15 +/- 110.07 ng/mL, P = 0.012) and systolic blood
      pressure (from 133.8 +/- 17.3 to 129.5 +/- 11.3 mm Hg, P = 0.024). In PD
      patients, lower doses and less frequent injection of CERA are sufficient to
      maintain Hgb at levels similar to those achieved by DA therapy, with improved
      iron utilization and reduced blood pressure. 

PMID- 25944558
TI  - Surface-engineered dendrimers in gene delivery.

PMID- 25944559
TI  - Interaction between the NS4B amphipathic helix, AH2, and charged lipid headgroups
      alters membrane morphology and AH2 oligomeric state--Implications for the
      Hepatitis C virus life cycle.
AB  - The non-structural protein 4B (NS4B) from Hepatitis C virus (HCV) plays a pivotal
      role in the remodelling of the host cell's membranes, required for the formation
      of the viral replication complex where genome synthesis occurs. NS4B is an
      integral membrane protein that possesses a number of domains vital for viral
      replication. Structural and biophysical studies have revealed that one of these,
      the second amphipathic N-terminal helix (AH2), plays a key role in these
      remodelling events. However, there is still limited understanding of the
      mechanism through which AH2 promotes these changes. Here we report on solid-state
      NMR and molecular dynamics studies that demonstrate that AH2 promotes the
      clustering of negatively charged lipids within the bilayer, a process that
      reduces the strain within the bilayer facilitating the remodelling of the lipid
      bilayer. Furthermore, the presence of negatively charged lipids within the
      bilayer appears to promote the disassociation of AH2 oligomers, highlighting a
      potential role for lipid recruitment in regulating NS protein interactions. 

PMID- 25944560
TI  - Antimicrobial 2-hydroxyisocaproic acid and chlorhexidine resist inactivation by
      dentine.
AB  - AIM: To compare the antibacterial activity of 2-hydroxyisocaproic acid (HICA)
      with currently used root canal medicaments and to examine their interactions with
      potential inhibitors in nutrient-deficient and nutrient-rich conditions.
      METHODOLOGY: First, the antibacterial activity of single concentrations of HICA,
      calcium hydroxide solution or slurry, chlorhexidine digluconate or acetate was
      tested against Enterococcus faecalis with and without potential inhibitors:
      dentine powder (DP), hydroxyapatite or bovine serum albumin, in a low
      concentration of peptone water. Relative viable counts were determined by culture
      at 1, 24 and 48 h. In the second set of experiments, the activity of three
      concentrations of HICA was evaluated against two isolates of E. faecalis with and
      without potential inhibitors in nutrient-rich thioglycollate broth using a
      modification of a standard microdilution method. The minimum bactericidal
      concentration was determined by culture at 1, 24 and 48 h. RESULTS:
      Concentrations of >=33 mg mL(-1) of HICA were found to be bactericidal against E.
      faecalis in both nutrient-deficient and nutrient-rich environments at 24- to 48-h
      incubation, whereas the initial activity of Ca(OH)2 slurry was lost at 48-h
      incubation. HICA tolerated well all tested potential inhibitors up to 19 mg mL(
      1) . DP concentrations higher than this inhibited its activity in a dose
      dependent manner in both environments. DP demonstrated moderate antibacterial
      activity, and it enhanced the otherwise limited activity of Ca(OH)2 slurry and
      solution. DP did not impact on the activity of chlorhexidine. CONCLUSIONS: These
      results support the long-term antibacterial activity of HICA and indicate its
      tolerance to clinically relevant concentrations of dentine and other inhibitors
      commonly present in the root canal system. Therefore, HICA may have potential as
      an interappointment medication in the treatment of root canal infections.

PMID- 25944561
TI  - A 7-day recall period for a clinical application of the oral health impact
      profile questionnaire.
AB  - OBJECTIVES: Aims were to investigate and compare the validity and reliability of
      Oral Health Impact Profile (OHIP) scores referencing 7-day and 1-month recall
      periods in international prosthodontic patients. MATERIAL AND METHODS: A sample
      of 267 patients (mean age = 54.0 years, SD = 17.2 years, 58 % women) with stable
      oral health-related quality of life was recruited from prosthodontic treatment
      centers in Croatia, Germany, Hungary, Japan, Slovenia, and Sweden. These patients
      completed the OHIP on two occasions using a new 7-day recall period and the
      traditional 1-month recall period. OHIP score validity and reliability were
      investigated with structural equation models (SEMs) that included OHIP(past 7
      days) and OHIP(1 month) latent factors and single indicator measures of global
      oral health status. The SEMs assessed measurement invariance and the relative
      validities of the two OHIP latent factors (representing the two recall periods).
      RESULTS: The SEMs provided cogent evidence for recall period measurement
      invariance for the two OHIP forms and equal validities (r = .48) with external
      measures of global oral health status. CONCLUSION: When assessed in international
      prosthodontic patients, OHIP scores using the new 7-day recall period were as
      reliable and valid as the scores using the 1-month recall period. CLINICAL
      RELEVANCE: Conceptual advantages make a 7-day recall period a preferred frame of
      reference in clinical applications of the OHIP questionnaire.

PMID- 25944562
TI  - Biomodulatory metronomic therapy induces PET-negative remission in chemo- and
      brentuximab-refractory Hodgkin lymphoma.

PMID- 25944563
TI  - Recovery of Staphylococcus aureus in Gray Mugil cephalus Roe (Bottarga):
      Investigation by an Integrated Cultural/Molecular Approach.
AB  - In the Mediterranean area, salted and dried roe from the gray Mugil cephalus
      "bottarga" represent a speciality food with great commercial value. Bottarga is
      currently produced by a traditional handmade process and, the risk of human
      bacterial contamination during its manufacturing is still unknown; in this
      perspective the foodborne pathogen Staphylococcus aureus could potentially
      contaminate this product due to poor sanitation or bad handling during
      processing. The aim of this work is: to evaluate the contamination level of
      foodborne pathogens at different product manufacturing stages and, in addition,
      to describe a fast and realizable method for the rapid detection of S. aureus in
      bottarga samples in the field. A cultural procedure was initially used to
      investigate the occurrence of S. aureus and the other main foodborne pathogens in
      bottarga samples at the different manufacturing stages (from roe to final
      product). In addition, a molecular approach was used to rapidly determine the
      presence of total bacteria, S. aureus, and its potential toxigenicity. Of the 194
      specimens analyzed, we identified: Clostridium perfringens, Enterococcus spp. and
      Enterobacteriaceae. However, some samples resulted as being contaminated with S.
      aureus (4% in roe and 8.7% in the final product). During the bottarga
      manufacturing process, we observed an increase in pathogen levels (from 10(2) to
      10(5) CFU/g) in contaminated samples, and entA and entB genotypes were
      identified. Reconstruction experiments suggest that the fresh roe and the
      bottarga (not completely dried) could represent a risk for the contamination and
      growth of pathogen bacteria. 

PMID- 25944564
TI  - Advanced biopolymer-coated drug-releasing titania nanotubes (TNTs) implants with
      simultaneously enhanced osteoblast adhesion and antibacterial properties.
AB  - Here, we report on the development of advanced biopolymer-coated drug-releasing
      implants based on titanium (Ti) featuring titania nanotubes (TNTs) on its
      surface. These TNT arrays were fabricated on the Ti surface by electrochemical
      anodization, followed by the loading and release of a model antibiotic drug,
      gentamicin. The osteoblastic adhesion and antibacterial properties of these TNT
      Ti samples are significantly improved by loading antibacterial payloads inside
      the nanotubes and modifying their surface with two biopolymer coatings (PLGA and
      chitosan). The improved osteoblast adhesion and antibacterial properties of these
      drug-releasing TNT-Ti samples are confirmed by the adhesion and proliferation
      studies of osteoblasts and model Gram-positive bacteria (Staphylococcus
      epidermidis). The adhesion of these cells on TNT-Ti samples is monitored by
      fluorescence and scanning electron microscopies. Results reveal the ability of
      these biopolymer-coated drug-releasing TNT-Ti substrates to promote osteoblast
      adhesion and proliferation, while effectively preventing bacterial colonization
      by impeding their proliferation and biofilm formation. The proposed approach
      could overcome inherent problems associated with bacterial infections on Ti-based
      implants, simultaneously enabling the development of orthopedic implants with
      enhanced and synergistic antibacterial functionalities and bone cell promotion. 

PMID- 25944565
TI  - Icatibant in angiotensin-converting enzyme (ACE) inhibitor-associated angioedema.
AB  - BACKGROUND: Angioedema occurs in up to 2% of those taking angiotensin-converting
      enzyme (ACE) inhibitors. Upper airway angioedema may potentially require
      endotracheal intubation or cricothyrotomy, and is usually unresponsive to
      adrenaline. The bradykinin receptor antagonist icatibant is proven to be
      effective in the treatment of acute attacks of hereditary angioedema, and has
      also been reported effective in the treatment of angioedema associated with ACE
      inhibitors. AIM: To describe the use of icatibant for ACE inhibitor-associated
      airway angioedema. METHODS: We treated 13 consecutive emergency department (ED)
      patients, who had not improved with adrenaline and/or corticosteroids, with
      icatibant 30 mg subcutaneously for ACE inhibitor-associated upper respiratory
      tract angioedema according to an agreed protocol. RESULTS: Four patients were
      intubated in the ED either before or after receiving icatibant; three of these
      were extubated within 24 h of treatment. Eight patients received early icatibant
      and did not require intubation. The time from onset of airway angioedema to ED
      presentation ranged from 1 h to 3 days (median 4 h); from ED presentation to
      receiving icatibant, from 30 minutes to 3 days (median 3 h); and to onset of
      symptom improvement after icatibant, 15 minutes to 7 h (median 2 h). One patient
      received a second dose of icatibant. CONCLUSION: All patients improved after
      receiving icatibant, consistent with its bradykinin receptor blocking mechanism.
      Icatibant rapidly reversed symptoms, and appeared to avert the need for
      intubation or expedite extubation. Timely use of icatibant in ACE inhibitor
      associated angioedema may avert the need for invasive airway procedures and
      intensive care unit admission.

PMID- 25944567
TI  - Effects of Citrus Flavonoids Against Microvascular Damage Induced by
      Hypoperfusion and Reperfusion in Rat Pial Circulation.
AB  - OBJECTIVE: The aim of the present study was to investigate the in vivo protective
      effects of hesperidin or diosmin or apigenin on damage induced by transient BCCAO
      and reperfusion. METHODS: Rat pial microcirculation was observed through a closed
      cranial window, using fluorescence microscopy. Pial arterioles were classified in
      five orders according to the Strahler's method. RESULTS: After 30 BCCAO and 60
      minutes reperfusion, rats showed decreased arteriolar diameter, microvascular
      leakage, leukocyte adhesion, and reduction in capillary perfusion. Hesperidin and
      diosmin abolished the reduction in arteriolar diameter, while higher dose
      apigenin induced dilation by 21.7 +/- 2.0% in order three arterioles RE. Nitric
      oxide synthase inhibition attenuated significantly hesperidin or diosmin or
      apigenin's effects on arteriolar diameter. Moreover, all these substances reduced
      microvascular leakage as well as leukocyte adhesion in dose-related manner, while
      capillary perfusion was protected. Furthermore, reduction in infarcted area and
      decrease in ROS production were observed. CONCLUSIONS: Hesperidin, diosmin, and
      apigenin showed dose-related protective effects on hypoperfusion-reperfusion
      injury, causing nitric oxide release and attenuating tissue edema and leukocyte
      adhesion.

PMID- 25944566
TI  - BET inhibitors induce apoptosis through a MYC independent mechanism and synergise
      with CDK inhibitors to kill osteosarcoma cells.
AB  - Osteosarcoma (OS) survival rates have plateaued in part due to a lack of new
      therapeutic options. Here we demonstrate that bromodomain inhibitors (BETi), JQ1,
      I-BET151, I-BET762, exert potent anti-tumour activity against primary and
      established OS cell lines, mediated by inhibition of BRD4. Strikingly, unlike
      previous observations in long-term established human OS cell lines, the
      antiproliferative activity of JQ1 in primary OS cells was driven by the induction
      of apoptosis, not cell cycle arrest. In further contrast, JQ1 activity in OS was
      mediated independently of MYC downregulation. We identified that JQ1 suppresses
      the transcription factor FOSL1 by displacement of BRD4 from its locus. Loss of
      FOSL1 phenocopied the antiproliferative effects of JQ1, identifying FOSL1
      suppression as a potential novel therapeutic approach for OS. As a monotherapy
      JQ1 demonstrated significant anti-tumour activity in vivo in an OS graft model.
      Further, combinatorial treatment approaches showed that JQ1 increased the
      sensitivity of OS cells to doxorubicin and induced potent synergistic activity
      when rationally combined with CDK inhibitors. The greater level of activity
      achieved with the combination of BETi with CDK inhibitors demonstrates the
      efficacy of this combination therapy. Taken together, our studies show that BET
      inhibitors are a promising new therapeutic for OS. 

PMID- 25944568
TI  - Rapid reduction of viruria and stabilization of allograft function by fusidic
      acid in a renal transplant recipient with JC virus-associated nephropathy.
AB  - JC virus (JCV)-associated nephropathy has been increasingly recognized as a cause
      of allograft dysfunction with graft loss in renal transplant recipients. Like
      many other opportunistic viral infections in transplant recipients, there are
      currently limited therapeutic options for this condition. Fusidic acid has
      previously been reported to exhibit antiviral activity against JCV in in vitro
      assays. We report the first in vivo study to document the rapid reduction of JC
      viruria and stabilization of allograft function by oral fusidic acid (fusidate
      sodium) in a deceased donor renal transplant recipient with JCV-associated
      nephropathy and acute allograft dysfunction which did not improve initially to
      surgical relief of hydronephrosis and reduction of immunosuppressants. Rapid
      reduction of JC viruria detected by quantitative PCR and stabilization of renal
      function were observed. Fusidic acid has several practical advantages in this
      clinical setting, including a low EC50 against JCV, high plasma C max, long half
      life, availability of both oral and intravenous formulations, excellent oral
      bioavailability, good patient tolerability, and lack of serious drug interactions
      with other drugs taken by renal transplant recipients. Further mechanistic and
      clinical studies are necessary to evaluate this treatment option for JCV
      associated nephropathy. 

PMID- 25944569
TI  - Eosinophilia a deux: a brain nagging souvenir from the Philippines.
AB  - Angiostrongylus cantonensis is the most common cause of eosinophilic meningitis.
      Although a rare condition among travelers, increased travel and global
      transportation of food products may result in more cases across non-endemic,
      developed countries in the future. We here describe two men with headache and
      painful skin after visiting the Philippines as presenting symptoms. Subsequently,
      confusion and focal neurologic symptoms developed. Both had increased serum
      eosinophils; however, CSF eosinophilia was only demonstrated after repeated
      lumbar puncture. In the CSF of both, Angiostrongylus spp. DNA was detected. Both
      were treated with albendazole combined with corticosteroids, after which symptoms
      improved. 

PMID- 25944570
TI  - A novel case of Raoultella planticola urinary tract infection in a female:
      comment on 'Nosocomial pneumonia caused by carbapenem-resistant Raoultella
      planticola: a case report and literature review'.

PMID- 25944571
TI  - The putative Ggamma subunit gene MGG1 is required for conidiation, appressorium
      formation, mating and pathogenicity in Magnaporthe oryzae.
AB  - Heterotrimeric G-proteins play key roles in the transduction of extracellular
      signals to various downstream effectors in eukaryotes. In our previous study, a T
      DNA insertional mutant A1-412, in which the promoter of a putative Ggamma subunit
      gene MGG1 was disrupted, was impaired in asexual/sexual sporulation, appressorium
      formation, and pathogenicity in Magnaporthe oryzae. Here the roles of MGG1 in
      regulating fungal development and plant infection were further investigated and
      verified using a gene deletion strategy. Targeted gene deletion mutants of MGG1
      exhibited similar phenotypes to those of A1-412. The Deltamgg1 mutants were
      unable to differentiate appressorium on hydrophobic surfaces and nonpathogenic to
      susceptible hosts. The defects of the Deltamgg1 mutants in appressorium formation
      were partially restored by adding exogenous cAMP or IBMX (a phosphodiesterase
      inhibitor), although the induced appressoria were still nonfunctional. Expressing
      Mgg1-GFP fusion protein in an Deltamgg1 mutant could complement all phenotypes of
      the mutant, and bright GFP fluorescence was observed at the periphery of fungal
      cells, indicating that Mgg1 mainly localizes to plasma membrane. Quantitative RT
      PCR analysis revealed that deletion of MGG1 resulted in a significant reduction
      in mRNA levels of the genes encoding Galpha (MagA, MagB, and MagC), Gbeta (Mgb1),
      and adenylate cyclase (Mac1). Moreover, intracellular cAMP accumulation was
      significantly reduced in Deltamgg1 mutants compared to that in the wild-type
      strain. Taken together, our results suggested that Ggamma subunit Mgg1 might act
      upstream of cAMP signaling pathway and play critical roles in regulation of
      conidiation, appressorium formation, mating, and plant infection in M. oryzae. 

PMID- 25944573
TI  - Predicting time to death after withdrawal of life-sustaining therapy.
AB  - PURPOSE: Predicting time to death following the withdrawal of life-sustaining
      therapy is difficult. Accurate predictions may better prepare families and
      improve the process of donation after circulatory death. METHODS: We
      systematically reviewed any predictive factors for time to death after withdrawal
      of life support therapy. RESULTS: Fifteen observational studies met our inclusion
      criteria. The primary outcome was time to death, which was evaluated to be within
      60 min in the majority of studies (13/15). Additional time endpoints evaluated
      included time to death within 30, 120 min, and 10 h, respectively. While most
      studies evaluated risk factors associated with time to death, a few derived or
      validated prediction tools. Consistent predictors of time to death that were
      identified in five or more studies included the following risk factors:
      controlled ventilation, oxygenation, vasopressor use, Glasgow Coma Scale/Score,
      and brain stem reflexes. Seven unique prediction tools were derived, validated,
      or both across some of the studies. These tools, at best, had only moderate
      sensitivity to predicting the time to death. Simultaneous withdrawal of all
      support and physician opinion were only evaluated in more recent studies and
      demonstrated promising predictor capabilities. CONCLUSIONS: While the risk
      factors controlled ventilation, oxygenation, vasopressors, level of
      consciousness, and brainstem reflexes have been most consistently found to be
      associated with time to death, the addition of novel predictors, such as
      physician opinion and simultaneous withdrawal of all support, warrant further
      investigation. The currently existing prediction tools are not highly sensitive.
      A more accurate and generalizable tool is needed to inform end-of-life care and
      enhance the predictions of donation after circulatory death eligibility.

PMID- 25944574
TI  - Clinical and imaging factors associated with severe complications of cervical
      necrotizing fasciitis.
AB  - PURPOSE: Cervical necrotizing fasciitis (CNF) is a severe and debilitating
      disease that requires intensive care unit (ICU) management and prompt surgical
      treatment to reduce morbidity and mortality. The aim of this study was to
      estimate the incidence and factors associated with severe complications of CNF.
      METHODS: We reviewed the medical records of consecutive patients hospitalized in
      an ICU from 2007 to 2012. The data were collected retrospectively; initial
      cervical and thoracic computed tomography (CT) scans, performed on admission,
      were reviewed by an experienced and blinded radiologist to determine CNF
      complications. RESULTS: A cohort of 160 patients admitted for CNF was included.
      The following complications of CNF were found: bilateral extension of CNF (28%),
      internal jugular vein thrombosis (21%), descending necrotic effusion (14%),
      mediastinitis (24%), and mortality (4%); 53% had at least one complication, and
      48% had at least one cervical complication. On the basis of a univariate
      analysis, the significant independent factors are odynophagia, dyspnea, oral
      glucocorticoids intake before admission, and pharyngeal source. Oral nonsteroidal
      anti-inflammatory drug intake before admission does not have any impact. The
      initial CNF complications increased both the duration of mechanical ventilation
      and the length of stay in the ICU. On the basis of a multivariate analysis, the
      independent factors for severe complications are pharyngeal CNF and oral
      glucocorticoid intake before admission. CONCLUSIONS: Our study demonstrated that
      an initial cervico-thoracic CT scan revealed a high incidence of cervical and
      mediastinal CNF complications that all needed immediate management. Those severe
      complications might be avoidable as they were associated, at least partially,
      with prehospital oral glucocorticoid intake.

PMID- 25944572
TI  - Sex-specific disruption of murine midbrain astrocytic and dopaminergic
      developmental trajectories following antenatal GC treatment.
AB  - The mammalian midbrain dopaminergic systems arising in the substantia nigra pars
      compacta (SNc) and ventral tegmental area (VTA) are critical for coping
      behaviours and are implicated in neuropsychiatric disorders where early life
      challenges comprise significant risk factors. Here, we aimed to advance our
      hypothesis that glucocorticoids (GCs), recognised key players in neurobiological
      programming, target development within these systems, with a novel focus on the
      astrocytic population. Mice received antenatal GC treatment (AGT) by including
      the synthetic GC, dexamethasone, in the mothers' drinking water on gestational
      days 16-19; controls received normal drinking water. Analyses of regional shapes
      and volumes of the adult SNc and VTA demonstrated that AGT induced long-term,
      dose-dependent, structural changes that were accompanied by profound effects on
      astrocytes (doubling/tripling of numbers and/or density). Additionally, AGT
      induced long-term changes in the population size and distribution of SNc/VTA
      dopaminergic neurons, confirming and extending our previous observations made in
      rats. Furthermore, glial/neuronal structural remodelling was sexually dimorphic
      and depended on the AGT dose and sub-region of the SNc/VTA. Investigations within
      the neonatal brain revealed that these long-term organisational effects of AGT
      depend, at least in part, on targeting perinatal processes that determine
      astrocyte density and programmed cell death in dopaminergic neurons.
      Collectively, our characterisation of enduring, AGT-induced, sex-specific
      cytoarchitectural disturbances suggests novel mechanistic links for the strong
      association between early environmental challenge (inappropriate exposure to
      excess GCs) and vulnerability to developing aberrant behaviours in later life,
      with translational implications for dopamine-associated disorders (such as
      schizophrenia, ADHD, autism, depression), which typically show a sex bias.

PMID- 25944575
TI  - Neuroprotection and cardioprotection after cardiac arrest: how cool is cool
      enough?

PMID- 25944576
TI  - Comparison of Indirect Nursing Interventions Performed by Korean and U.S. Nurses
      Using the Nursing Interventions Classification (NIC) System.
AB  - PURPOSE: The purposes of this study were to identify frequency and time spent
      performing indirect nursing interventions by Korean nurses, and to compare the
      time spent on indirect nursing interventions with estimates of time spent by U.S.
      nurses. METHODS: Data were collected from 721 registered nurses working in eight
      hospitals in Korea. U.S. data were obtained from the fifth edition of the Nursing
      Interventions Classification published in 2008. RESULTS: Korean nurses took more
      time with 4 interventions, and U.S. nurses took more time with 13. CONCLUSIONS:
      In general, Korean nurses spent less time performing indirect interventions than
      did U.S. nurses. IMPLICATION: Information from this study will help nurse
      administrators in their decision-making processes regarding managing units and
      staffing.

PMID- 25944578
TI  - Pharmacokinetic and pharmacodynamic evaluation of high doses of buprenorphine
      delivered via high-concentration formulations in cats.
AB  - OBJECTIVES: To evaluate the potential benefits of high-dose buprenorphine
      formulations for analgesia in cats, serial and crossover studies were undertaken
      to investigate their pharmacokinetics and thermal antinociceptive effects.
      METHODS: Twelve healthy adult domestic shorthair cats (6.0 +/- 1.1 kg body
      weight) were studied. Aqueous solutions of buprenorphine hydrochloride at 0,
      0.02, 0.06, 0.12 and 0.24 mg/kg body weight and formulations containing 0, 0.3,
      0.6 and 1.2 mg/ml with and without preservatives were given subcutaneously. Blood
      samples were taken and thermal threshold (TT) measured prior to and at regular
      time points up to 72 h after dosing. Descriptive statistics and analyses of
      variance were applied as appropriate. RESULTS: Baseline TT was 47.6 +/- 4.1
      degrees C, which increased in all groups treated with all buprenorphine dosages
      and formulations. After doses of 0.12 mg/kg and above, TT was significantly
      higher than baseline at most time points from 1-30 h post-treatment. The time to
      maximum effect (Tmax) ranged between 0.25 and 2.00 h; and plasma concentrations
      associated with maximum antinociceptive effect (Cmax) were 1.01-1.72 ng/ml after
      the 0.02 mg/kg dose, 1.4-4.9 ng/ml after the 0.06 mg/kg dose, 4.6-51.4 ng/ml
      after the 0.12 mg/kg dose and 5.3-22.3 ng/ml after the 0.24 mg/kg dose. The range
      of estimates for the buprenorphine elimination half-life were as follows: 0.02
      mg/kg = 1.35-5.33 h; 0.06 mg/kg = 16.1-31.2 h; 0.12 mg/kg = 10.1-34.0 h; and 0.24
      = mg/kg 16.1-31.6 h. The mean 'plasma concentration for the offset of analgesia'
      was 2.3 +/- 2.0 ng/ml. No adverse effects were seen. The addition of
      preservatives to a high-concentration buprenorphine formulation had no impact on
      antinociception nor any side effects. CONCLUSIONS AND RELEVANCE: Aqueous high
      concentration buprenorphine formulations administered at 0.12 or 0.24 mg/kg have
      potential for clinical use in cats, providing prolonged antinociception in a
      single subcutaneous injection of minimal dose volume.

PMID- 25944579
TI  - Evaluation of associations among Coxiella burnetii and reproductive abnormalities
      in cats.
AB  - OBJECTIVES: Coxiella burnetii is an obligate intracellular bacterium that is
      found worldwide, is associated or suggested to be associated with reproductive
      abnormalities in a number of species including cats, and is the cause of Q fever
      in humans. In a previous study, C burnetii DNA was amplified from the uterine
      tissues of 8.5% of client-owned cats in the USA but reproductive history was
      unknown and histopathological examination was not performed. In this study,
      uterine tissues of 26 normal cats and 11 cats with histopathological evidence of
      uterine disease or other reproductive abnormalities were evaluated for the
      presence of C burnetii. METHODS: A PCR assay that amplifies the repetitive
      transposon-like region (Trans 1 and 2) and a PCR assay that amplifies the IS-1111
      insertion sequence (IS-1111) were optimised and applied to the DNA extracts. The
      sensitivity threshold of both PCR assays was 12 pg/ul. Positive samples were
      evaluated for the presence of the organism using immunohistochemistry performed
      on paraffin-embedded tissue. RESULTS: Amplicons of the expected size developed in
      three samples (one from a cat with reproductive abnormalities) in the IS-1111
      assay; however, there was not enough DNA for sequence analysis.
      Immunohistochemical analysis was used to further evaluate these three samples and
      was negative for C burnetii. While C burnetii could not be confirmed by sequence
      analysis or immunohistochemistry, the PCR positive prevalence rate (8.1%) was
      similar to that published previously. CONCLUSIONS AND RELEVANCE: Biosafety
      precautions should be taken when working with cats that are aborting or
      parturient. Further research should be performed to evaluate the role that C
      burnetii may play in reproductive abnormalities in cats.

PMID- 25944577
TI  - Serum lipids and cardiac function correlate with nitrotyrosine and MMP activity
      in coronary artery disease patients.
AB  - AIMS: Peroxynitrite-matrix metalloproteinase (MMP) signalling has been shown to
      contribute to myocardial ischaemia/reperfusion injury and heart failure and to be
      influenced by hyperlipidaemia in preclinical models. Therefore, here we
      investigated the correlation between the markers of peroxynitrite-MMP signalling
      and hyperlipidaemia in patients with significant coronary stenosis. METHODS: Five
      minutes before percutaneous coronary intervention (PCI), arterial blood samples
      were collected from 36 consecutive patients with coronary artery disease (CAD)
      selected for elective PCI. RESULTS: Serum nitrotyrosine positively correlated
      with MMP-9 activity (r = 0.54, P = 0.01), but not with MMP-2 activity.
      Nitrotyrosine positively correlated with total (r = 0.58; P < 0.01) and LDL
      cholesterol (r = 0.55; P < 0.01), serum triglyceride (r = 0.47; P < 0.05), and
      creatinine (r = 0.42; P < 0.05) and negatively correlated with HDL cholesterol (r
      = -0.46; P < 0.05) and with left ventricular ejection fraction (LVEF; r = -0.55;
      P < 0.05), respectively. MMP-2 activity correlated positively with total (r =
      0.55; P < 0.05) and LDL cholesterol (r = 0.45; P < 0.05). In statin-treated
      patients, a significantly reduced serum nitrotyrosine was found as compared to
      statin naives; however, MMP activities and serum cholesterol levels were not
      different. MMP-9 activity correlated with urea nitrogen (r = 0.42; P < 0.05) and
      LVEF (r = -0.73; P < 0.01). Serum creatinine correlated negatively with LVEF (r =
      -0.50, P < 0.01). CONCLUSIONS: This is the first demonstration that (i) serum
      nitrotyrosine correlates with MMP-9 activity, (ii) lipid parameters correlate
      with nitrotyrosine and MMP-2 activity, (iii) myocardial function correlates with
      creatinine, nitrotyrosine and MMP-9 activity, and (iv) creatinine correlates with
      nitrotyrosine and urea nitrogen with MMP-9 activity in patients with CAD.
      Studying the biomarkers of peroxynitrite-MMP pathway in large prospective trials
      may reveal their diagnostic avails.

PMID- 25944580
TI  - Non-invasive evaluation of the haemodynamic effects of high-dose medetomidine in
      healthy cats for semen collection.
AB  - OBJECTIVES: This study aimed to assess non-invasively the cardiovascular effects
      of high-dose medetomidine on healthy male cats undergoing semen collection.
      METHODS: Haemodynamic evaluations were assessed on the basis of clinical
      examination, systolic arterial pressure (SAP) and transthoracic echocardiographic
      examination. Eight client owned, male domestic shorthair cats were sedated with a
      bolus of medetomidine intramuscularly (IM; 0.13 mg/kg), and semen collection was
      performed. A second transthoracic echocardiographic examination and SAP
      measurement were carried out 15 mins after sedation. At the end of the
      examination, the patients received a bolus of atipamezole (0.3 mg/kg) IM.
      RESULTS: The cats were deeply sedated, relaxed and laterally recumbent during the
      entire procedure. No rhythm abnormalities were observed during the examinations
      and no significant increase in SAP was recorded. Heart rate dropped from 200 +/-
      33 to 92 +/- 13.1 beats per min after sedation. There was a significant increase
      in left ventricular dimensions and the left atrial area. The parameters of left
      ventricular systolic function were reduced, as were systemic and pulmonary
      cardiac outputs. Peak diastolic wave velocities were significantly reduced, while
      isovolumic contraction and relaxation time of the left ventricle were prolonged.
      Aortic valve insufficiency was recorded for all cats, while mitral valve
      insufficiency was noted in five cats. None of the subjects developed systolic
      anterior motion of the mitral valve. CONCLUSIONS AND RELEVANCE: The protocol
      allowed us to collect good semen samples in healthy cats. However, high-dose
      medetomidine induces significant haemodynamic effects on the feline heart, mainly
      due to a reduced heart rate, an increased cardiac preload and impaired systolic
      function. The animals recovered from the anaesthesia, after antagonist
      administration, without showing any clinically relevant consequences.

PMID- 25944581
TI  - Highly pathogenic beta-hemolytic streptococcal infections in cats from an
      institutionalized hoarding facility and a multi-species comparison.
AB  - OBJECTIVES: Two hundred and thirty-four cats removed from an institutionalized
      hoarding facility (IHF) demonstrated severe, atypical pyogenic infections. The
      objective of this study was to document the various syndromes and determine the
      etiology of the infections. METHODS: All cats were evaluated initially after
      removal from the IHF and on a daily basis for at least 15 months. Samples were
      collected and sent for culture/susceptibility and histopathology to commercial
      laboratories or stored at -20(o)C. PCR was performed using universal bacterial
      primers to amplify the 16S-23S rRNA intergenic spacer region. PCR products were
      sequenced to determine the identity of the bacteria. RESULTS: Multiple pyogenic
      syndromes were documented, including abscesses of the paws and carpal/tarsal
      regions in 82 cats, acute rhinitis with profuse purulent nasal discharge in 68
      cats and cervical lymphadenitis with abscessation unassociated with any wounding
      in 51 cats. Many cats exhibited septic arthritis with total joint destruction,
      necrotizing fasciitis, meningitis, otitis and septic shock, often leading to
      death. These infections appeared to be caused by beta-hemolytic streptococci
      (BHS) based on initial culture results (n = 10), though speciation was unclear
      and some samples (n = 6) produced no growth. Based on PCR results (n = 26),
      Streptococcus canis was the only bacterial species or the dominant species
      identified in each sample, and was the only species present in all the regions
      associated with the pyogenic infections. CONCLUSIONS AND RELEVANCE: Horizontal
      gene transfer and loss of the cell wall may account for the discrepancy between
      the culture and PCR results and the highly pathogenic nature of S canis in this
      particular population of cats. A large-scale hoarding situation with multiple
      animal species, overcrowding, stress and mixing of animals from many geographical
      regions created ideal conditions for these events to occur. The specific
      virulence factors present may be more useful in predicting the pathophysiology of
      BHS infections than the species of Streptococcus found in the host per se.

PMID- 25944583
TI  - Circulating CD4+CD25-Foxp3+ cells are increased in patients with immune
      thrombocytopenia.

PMID- 25944582
TI  - Mucosal immunity induced by gliadin-presenting spores of Bacillus subtilis in HLA
      DQ8-transgenic mice.
AB  - The induction of mucosal immunity requires efficient antigen delivery and
      adjuvant systems. Probiotic bacterial strains are considered to be very promising
      tools to address both of these needs. In particular, Bacillus subtilis spores are
      currently under investigation as a long-lived, protease-resistant adjuvant system
      for different antigens. Furthermore, a non-recombinant approach has been
      developed based on the stable adsorption of antigen on the spore surface. In the
      present study, we explored this strategy as a means of modulating the immune
      response to wheat gliadin, the triggering agent of celiac disease (CD), an
      enteropathy driven by inflammatory CD4(+) T cells. Gliadin adsorption was tested
      on untreated or autoclaved wild-type (wt) and mutant (cotH or cotE) spores. We
      found that gliadin was stably and maximally adsorbed by autoclaved wt spores. We
      then tested the immune properties of the spore-adsorbed gliadin in HLA-DQ8
      transgenic mice, which express one of the two HLA heterodimers associated with
      CD. In vitro, spore-adsorbed gliadin was efficiently taken up by mouse dendritic
      cells (DCs). Interestingly, gliadin-pulsed DCs efficiently stimulated splenic
      CD4(+) T cells from mice immunised with spore-adsorbed gliadin. Nasal pre-dosing
      with spore-adsorbed gliadin failed to down-regulate the ongoing cellular response
      in gliadin-sensitised DQ8 mice. Notably, naive mice inoculated intranasally with
      multiple doses of spore-adsorbed gliadin developed an intestinal antigen-specific
      CD4(+) T cell-mediated response. In conclusion, our data highlight the ability of
      spore-adsorbed gliadin to elicit a T-cell response in the gut that could be
      exploitable for developing immune strategies in CD. 

PMID- 25944584
TI  - Correlates and motives of pre-drinking with intoxication and harm around licensed
      venues in two cities.
AB  - INTRODUCTION AND AIMS: The study investigates the prevalence of pre-drinking
      culture in the night-time economy (NTE) and its impact upon intoxication and
      alcohol-related harm and violence experienced by patrons. DESIGN AND METHODS:
      Cross-sectional surveys were conducted in and around licensed venues in Newcastle
      (NSW) and Geelong (Victoria) during peak trading hours (typically 9pm-1am).
      Participants completed a five minute structured interview which targeted:
      demographics, past and planned movements on the survey night, safety/experience
      of harm, and patron intoxication. 3949 people agreed to be interviewed, a
      response rate of 90.7%. Around half (54.9%) of interviewees were male and mean
      age was 24.4 years (SD = 5.8). RESULTS: 66.8% of participants reported pre
      drinking prior to attending licensed venues. On a 1-10 scale measuring self-rated
      intoxication, pre-drinkers scored significantly higher compared to non pre
      drinkers (P < 0.001). Compared to non-pre-drinkers, patrons who had consumed 6-10
      standard pre-drinks were 1.5 times more likely to be involved in a violent
      incident in the past 12 months (OR = 1.50, 95%CI 1.03-2.19, P = 0.037) increasing
      to 1.8 times more likely for patrons who had 11-15 drinks (OR = 1.80, 95%CI 1.04
      3.11 P = .036). Pre-drinking was also associated with both self-rated and
      observer-rated intoxication, as well as increased probability of illicit drug
      use. Amongst pre-drinkers, price was the most commonly reported motive for pre
      drinking (51.8%). DISCUSSION AND CONCLUSIONS: 'Pre-drinking' was normal behaviour
      in the current sample and contributes significantly to the burden of harm and
      intoxication in the NTE. Price disparity between packaged vs. venue liquor is a
      key motivator for pre-drinking.

PMID- 25944586
TI  - Partial trisomy 21: a fifty-year follow-up visit.
AB  - We describe a clinical encounter with family members that carry a balanced
      translocation involving chromosomes 15 and 21 roughly 50 years after the proband
      was diagnosed with partial trisomy 21 due to an unbalanced translocation. We
      discuss how these chromosomal rearrangements have impacted the lives of these
      individuals, and how they responded to revisiting their diagnoses after using
      updated cytogenetic techniques including high resolution chromosome banding and
      array comparative genomic hybridization.

PMID- 25944585
TI  - Validating CFD Predictions of Pharmaceutical Aerosol Deposition with In Vivo
      Data.
AB  - PURPOSE: CFD provides a powerful approach to evaluate the deposition of
      pharmaceutical aerosols; however, previous studies have not compared CFD results
      of deposition throughout the lungs with in vivo data. METHODS: The in vivo
      datasets selected for comparison with CFD predictions included fast and slow
      clearance of monodisperse aerosols as well as 2D gamma scintigraphy measurements
      for a dry powder inhaler (DPI) and softmist inhaler (SMI). The CFD model included
      the inhaler, a characteristic model of the mouth-throat (MT) and upper
      tracheobronchial (TB) airways, stochastic individual pathways (SIPs) representing
      the remaining TB region, and recent CFD-based correlations to predict
      pharmaceutical aerosol deposition in the alveolar airways. RESULTS: For the
      monodisperse aerosol, CFD predictions of total lung deposition agreed with in
      vivo data providing a percent relative error of 6% averaged across aerosol sizes
      of 1-7 MUm. With the DPI and SMI, deposition was evaluated in the MT, central
      airways (bifurcations B1-B7), and intermediate plus peripheral airways (B8
      through alveoli). Across these regions, CFD predictions produced an average
      relative error <10% for each inhaler. CONCLUSIONS: CFD simulations with the SIP
      modeling approach were shown to accurately predict regional deposition throughout
      the lungs for multiple aerosol types and different in vivo assessment methods.

PMID- 25944587
TI  - Dental, skeletal asymmetries and functional characteristics in Class II
      subdivision malocclusions.
AB  - Treatment outcomes of Angle Class II subdivision malocclusions may be compromised
      because of the uncertainty of the aetiology. Previous studies have reported
      controversial ideas about the origins, but the existence of a primary contributor
      still remains unknown. Functional factors have been mentioned as a probable
      cause, but until now, there have been no supporting data. This study was a cross
      sectional investigation of the characteristics of Angle Class II subdivision
      malocclusion, including dental, skeletal and functional factors, by comparison of
      the subdivision group and the normal occlusion group. The evaluations of dental
      and skeletal asymmetries of both groups were carried out by cone-beam computed
      tomography (CBCT) and analysis of dental casts. The functional deviations were
      evaluated by cast mounting and measuring. In the subdivision group, the
      asymmetric position of the glenoid fossa was found to be the most significant
      skeletal asymmetry. No dentoalveolar asymmetry was found in this group. The most
      important finding was that, in subdivision malocclusions, functional deviation
      resulting in pseudoasymmetry occurred in 32.86% of the study participants. This
      deviation is probably related to the disharmonious arch width between maxillary
      and mandibular dental arches in the premolar section. The origin of Angle Class
      II subdivision malocclusion is multifactorial, with dental, skeletal and
      functional factors included. Functional deviation occurs, probably due to dental
      arch width disharmony. Asymmetric position of the glenoid fossa may account for
      most of the skeletal asymmetry.

PMID- 25944589
TI  - Perceptions of single-visit and multiple-visit endodontic treatment: a survey of
      endodontic specialists and general dentists in Hong Kong.
AB  - AIM: To study the preference of practice for single- and multiple-visit
      endodontic treatment by Hong Kong endodontists and general dental practitioners
      (GDPs), and to investigate their reasons for choosing single- or multiple-visit
      treatment in their practice. METHOD: An anonymous questionnaire was mailed to all
      16 registered endodontists and 800 randomly selected GDPs in Hong Kong to explore
      their preference and reasons for selecting single- or multiple-visit endodontic
      treatment for their patients. Information on the use of magnifying loupes,
      microscopes and the number of years they have been in dental practice was also
      collected. RESULTS: Eight endodontists and 429 GDPs returned their questionnaires
      and the response rate was 50% and 53.6% respectively. Among the GDPs, 404 (94.2%)
      undertook endodontic treatment in their practices. For those performing
      endodontic treatment, the mean number of years of practice was 23.6 +/- 4.8 for
      endodontists and 15.3 +/- 9.1 for GDPs. Seven endodontists (87.5%) used a
      surgical microscope. For GDPs, only 25 (6.2%) used a surgical microscope and 123
      (30.4%) used magnifying loupes during endodontic treatment. Seven endodontists
      (87.5%) and 375 GDPs (92.8%) predominantly performed multiple-visit treatment.
      The commonest reasons for choosing multiple-visit treatment for both endodontists
      and GDPs were the positive effects of interappointment medications (n = 3, 37.5%)
      and that the tooth to be treated had doubtful prognosis (n = 103, 25.5%). The
      commonest reason for choosing single-visit treatment for both endodontists and
      general dentists was that treatment could be completed in one visit (n = 4, 50%)
      and (n = 127, 31.4%). CONCLUSION: Most Hong Kong endodontists and GDPs preferred
      offering multiple-visit endodontic treatment.

PMID- 25944590
TI  - Effect of endothelin receptor antagonists on clinically relevant outcomes after
      experimental subarachnoid hemorrhage: a systematic review and meta-analysis.
AB  - In clinical trials, endothelin receptor antagonists (ETRAs) reduced vasospasm but
      did not improve functional outcome after subarachnoid hemorrhage (SAH). We
      assessed the effects of treatment with ETRAs on clinically relevant outcomes in
      animal studies modelling SAH by performing a systematic review of the literature
      for controlled animal studies of ETRAs for the treatment of SAH. Primary outcomes
      were neurobehavioral outcomes and case fatality. Secondary outcomes were cerebral
      vasospasm and cerebral blood flow. Summary estimates were calculated using
      normalized mean difference random effects meta-analysis. We included 27 studies
      (55 experiments, 639 animals). Neurobehavioral scores were reported in none of
      the experiments, and case fatality in 8 (15%). Treatment with ETRAs was
      associated with a pooled odds ratio for case fatality of 0.61 (95% confidence
      interval (CI), 0.27 to 1.39); a 54% increase (95% CI, 39 to 69) in cerebral
      arterial diameter; and a 93% increase (95% CI, 58 to 129) in cerebral blood flow.
      We conclude that there is no evidence from animal studies that treatment with an
      ETRA improves clinically relevant outcomes after SAH. The reduction in cerebral
      vasospasm observed in animal studies is consistent with that observed in clinical
      trials, an effect that is not associated with better functional outcome in
      patients. 

PMID- 25944591
TI  - The brain metabolic activity after resuscitation with liposome-encapsulated
      hemoglobin in a rat model of hypovolemic shock.
AB  - We examined the effect of resuscitation with liposome-encapsulated hemoglobin
      (LEH) on cerebral bioenergetics in a rat model of 45% hypovolemia. The rats were
      resuscitated with isovolemic LEH or saline after 15 minutes of shock and followed
      up to 6 hours. Untreated hypovolemic rats received no fluid. The cerebral uptake
      of F-18-fluorodeoxyglucose (FDG) was measured by PET, and at 6 hours, the brain
      was collected for various assays. Hypovolemia decreased cellular adenosine
      triphosphate (ATP), phosphocreatine, nicotinamide adenine dinucleotide (NAD)/NADH
      ratio, citrate synthase activity, glucose-6-phosphate, and nerve growth factor
      (NGF), even when FDG uptake remained unchanged. The FDG uptake was reduced by
      saline, but not by LEH infusion. The reduced FDG uptake in saline group was
      associated with a decrease in hexokinase I expression. The LEH infusion
      effectively restored ATP content, NAD/NADH ratio, and NGF expression, and reduced
      the hypovolemia-induced accumulation of pyruvate and ubiquitinated proteins; in
      comparison, saline was significantly less effective. The LEH infusion was
      associated with low pH and high anion gap, indicating anionic gap acidosis. The
      results suggest that hypovolemic shock perturbs glucose metabolism at the level
      of pyruvate utilization, resulting in deranged cerebral energy stores. The
      correction of volume and oxygen deficits by LEH recovers the cerebral metabolism
      and creates a prosurvival phenotype. 

PMID- 25944594
TI  - The Effect of Arytenoidectomy on Functional and Oncologic Results of Supracricoid
      Partial Laryngectomy.
AB  - OBJECTIVE: The effect of arytenoid resection was investigated in patients who had
      undergone supracricoid partial laryngectomy (SCPL) by comparing functional and
      oncologic results between patients with both arytenoids preserved with those with
      one arytenoid resected. METHODS: Patients were divided into 2 groups: (1) both
      arytenoids preserved SCPL (BASCL) cases and (2) one arytenoid preserved SCPL
      (OASCL). The functional outcomes of the 2 groups were compared in terms of
      nasogastric tube removal time, decannulation time, incidence of aspiration
      pneumonia, and Performance Status Scale Scores for Head and Neck Cancer Patients
      for the late postoperative period. Additionally, the oncologic outcomes of both
      groups were compared using the 5-year local control rate, overall survival,
      disease-specific survival, and larynx preservation rate. RESULTS: Of the 68
      patients who were enrolled in the study, 20 of them were in the OASCL group and
      48 in BASCL group. There was no statistically significant difference in the early
      and late functional outcomes, and the oncologic outcomes were also similar.
      CONCLUSION: In addition to the proven oncologic safety, arytenoid resection does
      not increase the functional morbidity of the SCPL.

PMID- 25944593
TI  - Expanding applications, accuracy, and interpretation of laser speckle contrast
      imaging of cerebral blood flow.
AB  - Laser speckle contrast imaging (LSCI) provides a rapid characterization of
      cortical flow dynamics for functional monitoring of the microcirculation. The
      technique stems from interactions of laser light with moving particles. These
      interactions encode the encountered Doppler phenomena within a random
      interference pattern imaged in widefield, known as laser speckle. Studies of
      neurovascular function and coupling with LSCI have benefited from the real-time
      characterization of functional dynamics in the laboratory setting through
      quantification of perfusion dynamics. While the technique has largely been
      relegated to acute small animal imaging, its scalability is being assessed and
      characterized for both chronic and clinical neurovascular imaging. 

PMID- 25944595
TI  - Anticholinergic Use Is a Major Risk Factor for Dysphonia.
AB  - OBJECTIVE: We hypothesize that many cases of dysphonia of unclear etiology are a
      form of sicca caused by anticholinergic medication use, and we aim to determine
      their association. STUDY DESIGN: This was a cross-sectional study conducted over
      a 6-month time period. Participants were drawn from a tertiary care laryngology
      practice within an academic institution. METHODS: One hundred forty-nine patients
      met inclusion criteria. Patients rated the symptom of chronic hoarseness; scores
      were compared with participants' medication lists, comorbidities, age, and sex,
      and a multivariate logistic regression model was developed. Significance was set
      at P<.05. As a secondary analysis, participants rated a variety of other symptoms
      using the Voice Handicap Index-10, Reflux Symptom Index, and the GRBAS scale,
      which were likewise compared to anticholinergic use. RESULTS: Any patient taking
      at least 1 anticholinergic medication had a 2.32 increased odds (P=.03) of
      experiencing hoarseness. If the patient was taking 2 or more anticholinergic
      medications, those odds rose to 4.52 (P=.009). CONCLUSION: This is the first
      study, to our knowledge, that implicates medication use as a major risk factor
      for dysphonia of unclear etiology. An awareness of this association is invaluable
      when attributing cause to hoarseness and when considering treatment options.

PMID- 25944596
TI  - Transoral Sclerotherapy for Deep Space Cervical Lymphatic Malformations in
      Children With Acute Airway Compromise.
AB  - INTRODUCTION: Cervical lymphatic malformations in children rarely present with
      acute airway compromise. During an acute exacerbation or hemorrhage, lymphatic
      malformations involving the deep neck spaces may precipitate critical airway
      obstruction. These are rare clinical entities and tracheotomy is the standard
      procedure to bypass impending airway obstruction. METHODS: We present our recent
      experience with 2 children presenting with acute airway compromise resulting from
      deep space cervical lymphatic malformations and describe our technique and
      success with transoral sclerotherapy. RESULTS: Direct laryngoscopy-assisted
      transoral sclerotherapy with doxycycline may be considered an alternative to
      tracheotomy to address retropharyngeal and parapharyngeal space lymphatic
      malformations. CONCLUSIONS: Direct laryngoscopy-assisted transoral sclerotherapy
      is an excellent treatment option for children with deep space cervical lymphatic
      malformations with airway compromise. It is effective, provides direct access,
      and can be an alternative to a tracheotomy.

PMID- 25944597
TI  - Supraglottoplasty in Infants: A Staged Approach.
AB  - OBJECTIVE: While generally well tolerated for the treatment of severe
      laryngomalacia, bilateral supraglottoplasty has potential complications including
      supraglottic stenosis and aspiration. We report a more conservative staged
      supraglottoplasty in infants with severe laryngomalacia. METHODS: A retrospective
      review was performed of our patients who underwent staged supraglottoplasty from
      June 2007 to June 2012. Fifteen infants were identified and scored based on
      stridor, retractions, oxygen saturation, and feeding quality. Outcomes were
      compared with those reported in the literature for conventional bilateral
      supraglottoplasty. RESULTS: Seventy-three percent had significant improvement or
      resolution of stridor following the first stage of surgery and 100% in those
      undergoing a second stage. Twelve patients (80%) had mild to no retractions
      following one procedure and 100% had resolution after a second surgery. All 6
      patients with recurrent preoperative desaturations had resolution after the first
      stage of surgery. Of the 11 infants who had preoperative moderate-severe feeding
      problems, 9 of them (82%) had resolution after one surgery and the remaining 2
      had resolution after a second surgery. There were no complications in any of the
      patients. CONCLUSIONS: Staged supraglottoplasty appears to be an effective, low
      risk method to treat severe laryngomalacia. A second procedure was only required
      in 40% of patients.

PMID- 25944592
TI  - Ischemic brain injury in cerebral amyloid  angiopathy.
AB  - Cerebral amyloid angiopathy (CAA) is a common form of cerebral small vessel
      disease and an important risk factor for intracerebral hemorrhage and cognitive
      impairment. While the majority of research has focused on the hemorrhagic
      manifestation of CAA, its ischemic manifestations appear to have substantial
      clinical relevance as well. Findings from imaging and pathologic studies indicate
      that ischemic lesions are common in CAA, including white-matter hyperintensities,
      microinfarcts, and microstructural tissue abnormalities as detected with
      diffusion tensor imaging. Furthermore, imaging markers of ischemic disease show a
      robust association with cognition, independent of age, hemorrhagic lesions, and
      traditional vascular risk factors. Widespread ischemic tissue injury may affect
      cognition by disrupting white-matter connectivity, thereby hampering
      communication between brain regions. Challenges are to identify imaging markers
      that are able to capture widespread microvascular lesion burden in vivo and to
      further unravel the etiology of ischemic tissue injury by linking structural
      magnetic resonance imaging (MRI) abnormalities to their underlying
      pathophysiology and histopathology. A better understanding of the underlying
      mechanisms of ischemic brain injury in CAA will be a key step toward new
      interventions to improve long-term cognitive outcomes for patients with CAA.

PMID- 25944598
TI  - [News in histopathological diagnostics of precancerous lesions and tumors of the
      female genital tract].
AB  - OBJECTIVE: Introduce the news in histopathological diagnostics of gynecologic
      malignancies and their precursors. SUBJECT: Review. SETTING: Department of
      Pathology, First Faculty of Medicine and General University Hospital, Charles
      University, Prague. CONCLUSION: Better understanding of etiopathogenetic
      processes leads to changes in histopathological diagnosis, which have a direct
      impact on treatment.

PMID- 25944599
TI  - [Recommendation for genetic testing in patients suffering from gynecological
      malignancy].
AB  - OBJECTIVE: To present an overview of indications and recommendations for genetic
      testing in patients with hereditary susceptibility to develop malignant
      gynecological tumors. SUBJECT: Review. SETTING: Gynecological Oncology Center,
      Department of Obstetrics and Gynecology, Charles University, First Faculty of
      Medicine and General Faculty Hospital, Prague. SUBJECT AND METHOD: Literature
      review and recommendations for practice based on evidence and clinical
      experience. CONCLUSION: Women with hereditary susceptibility to malignant
      gynecological tumors represent only a relatively small part of the population.
      However, it is a well-defined risk factor and set of preventive and prophylactic
      measures can minimize the risk of cancer development (or risk of death from
      tumor). Knowledge of the indications for genetic testing is one of the basic
      knowledge of every gynecologist.

PMID- 25944600
TI  - [Specifics of medical care for lesbians].
AB  - OBJECTIVE: Health care for lesbian women, especially care within the competence
      of the gynecologist, general practitioner and sexologist, at first glance no
      different from heterosexual women care about, and in many issues this is really
      true. But there are a few specifics that differentiate this minority group. If
      the doctor realizes these specifics, he can offer a better care about the health
      of their patients and possibly also focus on the prevention of various diseases
      targeted prevention. This article points out the various specifics and their
      importance in the care of minority lesbian and bisexual women. DESIGN: Review
      article. SETTING: Centrum Medical s.r.o., Andrology and Sexology Clinic, Olomouc.
      METHODS: Analysis of literature review and our own experience dealing with
      differences of health care for lesbian women. CONCLUSION: Although
      physiologically and anatomical-ly lesbian, bisexual and heterosexual women are
      the same, studies show that certain diseases or risk in the population of
      lesbians and bisexual women are more prevalent and hence the need to particularly
      focus on preventive care for certain specifics.

PMID- 25944601
TI  - [Birth hypoxia].
AB  - OBJECTIVE: Evaluation of the commonly used laboratory and clinical parameters of
      the newborn shortly after birth. Check thresholds acidemia, and in relation to
      the method of termination of pregnancy. DESIGN: Retrospective epidemiological
      study. SETTING: Department of Obstetrics and Gynecology, University Hospital,
      Olomouc. METHODS: Of the 26,869 children born in the years 2000 to 2013 Inclusion
      criteria (complete clinical and laboratory findings after birth) fulfill 23,471
      (87.4%) neonates. Methods for evaluation of newborns included Apgar score
      calculation and arterial umbilical cord blood pH and lactate analysis. RESULTS: A
      total of 0.7% (157) of the neonates had severe acidosis pH below 7.00 arterial
      umbilical cord blood, its prevalence varies annually between 0.1 to 1.1%. Cutoff
      lactate in relation to pH < 7.00 was 6.3 mmol/l (n = 23 471, the sensitivity of
      92.99%, specificity 92.15%, AUC = 0.972). For children of low weight < 2500 g the
      cutoff value is lower, 5.3 mmol/l (n = 2592, 89.66% sensitivity, specificity
      91.10% AUC = 0.912). Suprathreshold lactate values was 8.4% (1977) newborns.
      Correlation of pH and lactate to Apgar evaluation is very low and in the range
      from 1 to 10 minutes gradually decreases. Worse Apgar evaluation in children of
      low birth weight do not correspond to laboratory findings acidosis, which is
      probably related to prematurity and lower energy reserves. Operating cesarean
      births in particular accounts for more than half of those with worse clinical
      findings Apgar and pH <7.00, but only 30% supratreshold lactate values. Also
      worse clinical evaluation after caesarean section is not in accordance with the
      laboratory findings. Vaginal surgery, especially forceps have a significant share
      of severe acidosis than cesarean, regardless of their frequency. Risk factor of
      forceps to pH less 7.00,OR = 9.28 (5.39 -15.77), P = 0.0000000, while caesarean
      to pH less 7,00 had OR = 1.52 (1.08 to 2.14), P = 0.01408156. CONCLUSION: The
      results obtained confirm that acidosis after birth is quite common, although they
      may not have response on the clinical condition of the newborn after birth.
      Evaluation of Apgar is little objective for the detection of hypoxia during birth
      and is influenced by the immaturity of newborn and method of delivery. Lactate
      levels may contribute to an objective assessment of hypoxia during birth. Values
      above 6.3 mmol/l can be considered an important indicator of newborn acidosis and
      birth hypoxia.

PMID- 25944602
TI  - [Analgesia for labour in the Czech Republic in the year 2011 from the perspective
      of OBAAMA-CZ study - prospective national survey].
AB  - GOAL OF THE STUDY: The aim of national survey was to describe current practice
      for analgesia during labour provided by anaesthesiologists in the Czech Republic
      (CZE). TYPE OF THE STUDY: National prospective observational. SETTING: 49
      obstetric departments in CZE. METHODS: We aimed to enrol all 97 obstetric
      departments in CZE and to monitor every case of anaesthetic care in peripartum
      period during November 2011. Data were recorded to Case Report Form with two
      parts (Demography 2010 and Case Report) into TrialDB database (Yale University,
      USA; adapted IBA, MU, CZE). Demographic data for CZE were obtained on request by
      UZIS. The data were analysed using SPSS 22. RESULTS: We enrolled 1943 cases of
      anaesthesiological care and 579 (29.8%) of them was to relief labour pain.
      Population and center weighted estimate of incidence of epidural labour analgesia
      was 12.5% (95% CI: 10.6% - 14.4%). Epidural analgesia was the most frequently
      applied via Tuohy needle G18 (97.8%), with administration of an epidural catheter
      G20 (95.7%), via medial approach (98.8%), in lateral position (76.7%) by the loss
      of resistance method (94.3%). All administrations of epidural analgesia were
      started by initial bolus, only in 28.2% of cases were followed continously.
      Always has been applied mixture of local anaesthetic with sufentanil at a dose of
      3-10 mcg. Bupivacaine was most frequently used local anaesthetic (80.7%),
      followed by levobupivacaine (12.6%). Median concentrations both bupivacaine and
      levobupivacaine were 0.125% (min. 0.1%, max. 0.3%).The most common complication
      of epidural analgesia was repeated puncture (21.2%), blood in the catheter
      (1.4%), blood in the needle (1.2%), unintended puncture of the dura mater (0.7%)
      and transient paresthesias (0.5%). CONCLUSION: In comparison to previously
      published data there was trend for lower incidence of epidural analgesia for
      labour in the CZE.

PMID- 25944603
TI  - [Changes in the levels of selected metabolites in the culture medium as a
      possible tool for the embryo selection in assisted reproduction].
AB  - Despite the increasing success of infertility treatment methods of assisted
      reproduction, it still remains a problem how to select the best embryo that has
      the potential for further development and implantation. At the present time,
      embryo selection is based especially on morphological criteria. This approach is
      subjective; therefore there is a trend to find another more objective and robust
      method for embryo selection. Embryo metabolism can be used as an indicator of
      viability. This non-invasive method allows observing changes in the levels of
      different metabolites in culture medium before and after incubation of the only
      one embryo. The most mentioned substances are carbohydrates and amino acids as
      important components of culture medium. Carbohydrates serve predominantly as
      energy sources, whereas amino acids are precursors of protein and nucleotides,
      antioxidants, osmolytes, pH regulators etc. Several methods have been proposed
      for evaluating of embryo metabolic profile of embryo. There are many hypotheses
      for embryo selection according its metabolic profile. 

PMID- 25944604
TI  - Giant placental chorioangioma with favorable outcome: a case report and
      literature review of literature.
AB  - OBJECTIVE: To describe a case of prenatal diagnosis of a giant placental
      chorioangioma with favorable outcome. DESIGN: A case report. SETTING: Gynecology
      and Obstetrics Service, Federal University of Triangulo Mineiro (UFTM), Uberaba
      MG, Brazil. CASE REPORT: The placental chorioangioma is the most common benign
      tumor, but the type giant has a small prevalence, ranging from 1:16.000 to
      1:50.000 pregnancies. We reported a case of a patient aged 18, pregnant for the
      first time, who performed a routine obstetric ultrasound was found to have
      polyhydramnios associated with placental vascular lesions suggestive of
      chorioangioma also was defined by fetal magnetic resonance imaging and confirmed
      by pathological examination.

PMID- 25944605
TI  - Changes in placental angiogenesis and their correlation with foetal intrauterine
      restriction.
AB  - TYPE OF STUDY: Summary review. SETTING: Department of Gynaecology and Obstetrics,
      1st Faculty of Medicine, Charles University and Hospital Na Bulovce, Prague;
      Department of Physiology, Faculty of Science, Charles University, Prague;
      Department of Children and Adolescent Medicine, 1st Faculty of Medicine, Charles
      University in Prague and General Teaching Hospital, Prague. INTRODUCTION:
      Intrauterine growth restriction (IUGR) is one of the most common problems in
      obstetrics. Its incidence is ranging between 3-10%, according to the type of
      study population and chosen criteria. The cutoff value mainly used for defining
      the IUGR is weight below the 10th percentile for gestational age. The minority of
      authors defines the cutoff value under the 5th or 3rd percentile. Any
      pathological interference with normal vascular development of placenta may have a
      critical impact on foetal growth and development. Ischaemia is the most common
      cause of IUGR in normally well-supplied placenta. IUGR is then a consequence of
      insufficient extension, branching, and dilatation of capillary loops during the
      formation of terminal villi. METHODS: This paper is a review focused on up-to
      date-known data concerning changes in placental angiogenesis and their impact on
      IUGR development. CONCLUSION: The aim of this review is to summarize the
      knowledge concerning the mechanisms of development of the vascular supply to the
      placenta under physiological conditions and in conditions that result in IUGR.

PMID- 25944606
TI  - [Measurement of gestational sac volume in the first trimester of pregnancy].
AB  - OBJECTIVE: The aim of our study was to measure the volume of gestational sac and
      amniotic sac in physiological pregnancies and missed abortion. We wanted to
      create nomograms for individual weeks of gestation. DESIGN: Retrospective cohort
      study. SETTING: Institute for the Care of Mother and Child, Prague. METHODS: The
      study randomized 413 women after spontaneous conception. The patients were
      divided into two groups: women with physiological pregnancy and childbirth in the
      period (374), and women with pregnancy terminated by missed abortion. Both groups
      were performed measurement volume of gestational and amniotic sac in the first
      trimester of pregnancy. Analysis was performed using 4D View software
      applications, and volume calculations were performed using VOCAL (Virtual Organ
      Computer Aided anaLysis). RESULTS: We have created the first in the Czech
      Republic nomograms volumes of gestational and amniotic sac in physiological
      pregnancies and missed abortion. We performed a correlation between the size of
      gestational sac and prosperity pregnancy. CONCLUSION: In our study we found no
      correlation between the volume of gestational sac and the development of the
      pregnancy.

PMID- 25944607
TI  - [Bulking agents in the treatment of the stress urinary incontinence - current
      state and future perspectives].
AB  - A review focused on minimally invasive treatment of the stress urinary
      incontinence using bulking agents provides a summary of the current knowledge on
      this subjects. This paper summarizes the findings on the mechanism of action,
      indications and applications technique, as well as clinical data on the efficacy
      and safety of the currently available bulking agents. Attention is also paid to
      possible future trends of this method. The work is designed to include specific
      implications for clinical practice. 

PMID- 25944608
TI  - [Ovaria borderline tumor - fertility-sparing surgery; case report].
AB  - The borderline tumors are known as low malignant potential tumors. Usually
      younger women suffer for them, than by the invasive ovarian carcinoma. They often
      which to be pregnant. The fertility-sparing surgery is posile but contain higher
      risk of the new disease on contralateral ovary.

PMID- 25944609
TI  - Direct Enantioselective Vinylogous Mannich Reaction of Ketimines with gamma
      Butenolide by Using Cinchona Alkaloid Amide/Zinc(II) Catalysts.
AB  - A direct enantioselective vinylogous Mannich reaction of ketimines with gamma
      butenolide has been developed. Good yields and enantioselectivities were observed
      for the reaction of various ketimines by using a cinchona alkaloid amide/Zn(OTf)2
      catalyst and Et3N. Both enantiomers of the products could be obtained by using
      pseudoenantiomeric chiral catalysts.

PMID- 25944610
TI  - A wavelet-based estimator of the degrees of freedom in denoised fMRI time series
      for probabilistic testing of functional connectivity and brain graphs.
AB  - Connectome mapping using techniques such as functional magnetic resonance imaging
      (fMRI) has become a focus of systems neuroscience. There remain many statistical
      challenges in analysis of functional connectivity and network architecture from
      BOLD fMRI multivariate time series. One key statistic for any time series is its
      (effective) degrees of freedom, df, which will generally be less than the number
      of time points (or nominal degrees of freedom, N). If we know the df, then
      probabilistic inference on other fMRI statistics, such as the correlation between
      two voxel or regional time series, is feasible. However, we currently lack good
      estimators of df in fMRI time series, especially after the degrees of freedom of
      the "raw" data have been modified substantially by denoising algorithms for head
      movement. Here, we used a wavelet-based method both to denoise fMRI data and to
      estimate the (effective) df of the denoised process. We show that seed voxel
      correlations corrected for locally variable df could be tested for false positive
      connectivity with better control over Type I error and greater specificity of
      anatomical mapping than probabilistic connectivity maps using the nominal degrees
      of freedom. We also show that wavelet despiked statistics can be used to estimate
      all pairwise correlations between a set of regional nodes, assign a P value to
      each edge, and then iteratively add edges to the graph in order of increasing P.
      These probabilistically thresholded graphs are likely more robust to regional
      variation in head movement effects than comparable graphs constructed by
      thresholding correlations. Finally, we show that time-windowed estimates of df
      can be used for probabilistic connectivity testing or dynamic network analysis so
      that apparent changes in the functional connectome are appropriately corrected
      for the effects of transient noise bursts. Wavelet despiking is both an algorithm
      for fMRI time series denoising and an estimator of the (effective) df of denoised
      fMRI time series. Accurate estimation of df offers many potential advantages for
      probabilistically thresholding functional connectivity and network statistics
      tested in the context of spatially variant and non-stationary noise. Code for
      wavelet despiking, seed correlational testing and probabilistic graph
      construction is freely available to download as part of the BrainWavelet Toolbox
      at www.brainwavelet.org.

PMID- 25944611
TI  - Domain-general involvement of the posterior frontolateral cortex in time-based
      resource-sharing in working memory: An fMRI study.
AB  - Working memory is often defined in cognitive psychology as a system devoted to
      the simultaneous processing and maintenance of information. In line with the time
      based resource-sharing model of working memory (TBRS; Barrouillet and Camos,
      2015; Barrouillet et al., 2004), there is accumulating evidence that, when memory
      items have to be maintained while performing a concurrent activity, memory
      performance depends on the cognitive load of this activity, independently of the
      domain involved. The present study used fMRI to identify regions in the brain
      that are sensitive to variations in cognitive load in a domain-general way. More
      precisely, we aimed at identifying brain areas that activate during maintenance
      of memory items as a direct function of the cognitive load induced by both verbal
      and spatial concurrent tasks. Results show that the right IFJ and bilateral
      SPL/IPS are the only areas showing an increased involvement as cognitive load
      increases and do so in a domain general manner. When correlating the fMRI signal
      with the approximated cognitive load as defined by the TBRS model, it was shown
      that the main focus of the cognitive load-related activation is located in the
      right IFJ. The present findings indicate that the IFJ makes domain-general
      contributions to time-based resource-sharing in working memory and allowed us to
      generate the novel hypothesis by which the IFJ might be the neural basis for the
      process of rapid switching. We argue that the IFJ might be a crucial part of a
      central attentional bottleneck in the brain because of its inability to upload
      more than one task rule at once. 

PMID- 25944612
TI  - Structured sparsity for spatially coherent fibre orientation estimation in
      diffusion MRI.
AB  - We propose a novel formulation to solve the problem of intra-voxel reconstruction
      of the fibre orientation distribution function (FOD) in each voxel of the white
      matter of the brain from diffusion MRI data. The majority of the state-of-the-art
      methods in the field perform the reconstruction on a voxel-by-voxel level,
      promoting sparsity of the orientation distribution. Recent methods have proposed
      a global denoising of the diffusion data using spatial information prior to
      reconstruction, while others promote spatial regularisation through an additional
      empirical prior on the diffusion image at each q-space point. Our approach
      reconciles voxelwise sparsity and spatial regularisation and defines a spatially
      structured FOD sparsity prior, where the structure originates from the spatial
      coherence of the fibre orientation between neighbour voxels. The method is shown,
      through both simulated and real data, to enable accurate FOD reconstruction from
      a much lower number of q-space samples than the state of the art, typically 15
      samples, even for quite adverse noise conditions. 

PMID- 25944613
TI  - Nature of functional links in valuation networks differentiates impulsive
      behaviors between abstinent heroin-dependent subjects and nondrug-using subjects.
AB  - Advanced neuroimaging studies have identified brain correlates of pathological
      impulsivity in a variety of neuropsychiatric disorders. However, whether and how
      these spatially separate and functionally integrated neural correlates
      collectively contribute to aberrant impulsive behaviors remains unclear. Building
      on recent progress in neuroeconomics toward determining a biological account of
      human behaviors, we employed resting-state functional MRI to characterize the
      nature of the links between these neural correlates and to investigate their
      impact on impulsivity. We demonstrated that through functional connectivity with
      the ventral medial prefrontal cortex, the delta-network (regions of the executive
      control system, such as the dorsolateral prefrontal cortex) and the beta-network
      (regions of the reward system involved in the mesocorticolimbic pathway), jointly
      influence impulsivity measured by the Barratt impulsiveness scale scores. In
      control nondrug-using subjects, the functional link between the beta- and delta
      networks is balanced, and the delta-network competitively controls impulsivity.
      However, in abstinent heroin-dependent subjects, the link is imbalanced, with
      stronger beta-network connectivity and weaker delta-network connectivity. The
      imbalanced link is associated with impulsivity, indicating that the beta- and
      delta-networks may mutually reinforce each other in abstinent heroin-dependent
      subjects. These findings of an aberrant link between the beta- and delta-networks
      in abstinent heroin-dependent subjects may shed light on the mechanism of
      aberrant behaviors of drug addiction and may serve as an endophenotype to mark
      individual subjects' self-control capacity. 

PMID- 25944615
TI  - Hierarchically mesoporous CuO/carbon nanofiber coaxial shell-core nanowires for
      lithium ion batteries.
AB  - Hierarchically mesoporous CuO/carbon nanofiber coaxial shell-core nanowires
      (CuO/CNF) as anodes for lithium ion batteries were prepared by coating the
      Cu2(NO3)(OH)3 on the surface of conductive and elastic CNF via electrophoretic
      deposition (EPD), followed by thermal treatment in air. The CuO shell stacked
      with nanoparticles grows radially toward the CNF core, which forms hierarchically
      mesoporous three-dimensional (3D) coaxial shell-core structure with abundant
      inner spaces in nanoparticle-stacked CuO shell. The CuO shells with abundant
      inner spaces on the surface of CNF and high conductivity of 1D CNF increase
      mainly electrochemical rate capability. The CNF core with elasticity plays an
      important role in strongly suppressing radial volume expansion by inelastic CuO
      shell by offering the buffering effect. The CuO/CNF nanowires deliver an initial
      capacity of 1150 mAh g(-1) at 100 mA g(-1) and maintain a high reversible
      capacity of 772 mAh g(-1) without showing obvious decay after 50 cycles. 

PMID- 25944614
TI  - Cortical maturation and myelination in healthy toddlers and young children.
AB  - The maturation of cortical structures, and the establishment of their
      connectivity, are critical neurodevelopmental processes that support and enable
      cognitive and behavioral functioning. Measures of cortical development, including
      thickness, curvature, and gyrification have been extensively studied in older
      children, adolescents, and adults, revealing regional associations with cognitive
      performance, and alterations with disease or pathology. In addition to these
      gross morphometric measures, increased attention has recently focused on
      quantifying more specific indices of cortical structure, in particular
      intracortical myelination, and their relationship to cognitive skills, including
      IQ, executive functioning, and language performance. Here we analyze the
      progression of cortical myelination across early childhood, from 1 to 6 years of
      age, in vivo for the first time. Using two quantitative imaging techniques,
      namely T1 relaxation time and myelin water fraction (MWF) imaging, we
      characterize myelination throughout the cortex, examine developmental trends, and
      investigate hemispheric and gender-based differences. We present a pattern of
      cortical myelination that broadly mirrors established histological timelines,
      with somatosensory, motor and visual cortices myelinating by 1 year of age; and
      frontal and temporal cortices exhibiting more protracted myelination.
      Developmental trajectories, defined by logarithmic functions (increasing for MWF,
      decreasing for T1), were characterized for each of 68 cortical regions.
      Comparisons of trajectories between hemispheres and gender revealed no
      significant differences. Results illustrate the ability to quantitatively map
      cortical myelination throughout early neurodevelopment, and may provide an
      important new tool for investigating typical and atypical development.

PMID- 25944616
TI  - Filamin A phosphorylation by Akt promotes cell migration in response to arsenic.
AB  - We had previously reported that trivalent arsenic (As(3+)), a well-known
      environmental carcinogen, induces phosphorylation of several putative Akt
      substrates. In the present report, we characterized one of these substrates by
      immunoprecipitation and proteomics analysis. The results indicate that a
      cytoskeleton remodeling protein, filamin A, with a molecular weight around 280
      kDa, is phosphorylated by Akt in HEK-293 cells treated with As(3+), which was
      also confirmed in human bronchial epithelial cell line, BEAS-2B cells. Additional
      biochemical and biological studies revealed that serine 2152 (S2152) of filamin A
      is phosphorylated by activated Akt in the cells treated with As(3+). To further
      confirm the importance of Akt-dependent filamin A S2152 phosphorylation in As(3+)
      induced cell migration, we over-expressed either wild type filamin A or the
      mutated filamin A in which the S2152 was substituted with alanine (S2152A). The
      capability of cell migration was reduced significantly in the cells expressing
      the mutated filamin A (S2152A). Clinically, we found that increased expression of
      filamin A predicts poorer overall survival of the lung cancer patients with
      adenocarcinoma. Thus, these data suggest that Akt dependent filamin A
      phosphorylation is one of the key events in mediating As(3+)-induced
      carcinogenesis. Antagonizing Akt signaling can ameliorate As(3+)-induced filamin
      A phosphorylation and cell migration, which may serve as a molecular targeting
      strategy for malignancies associated with environmental As(3+) exposure.

PMID- 25944617
TI  - The predictive value of ERCC1 and p53 for the effect of panobinostat and
      cisplatin combination treatment in NSCLC.
AB  - Cisplatin is one of the most common chemotherapeutic drugs for non-small cell
      lung cancer (NSCLC). However, the response rate is limited because of drug
      resistance. Histone deacetylase inhibitors (HDACis), which can alter DNA
      accessibility by regulating chromatin structure and inducing apoptosis, exhibit a
      synergistic action with cisplatin. However, no biomarkers that can predict the
      efficacy of the combination of HDACis and cisplatin have been reported. Our study
      found that panobinostat, an HDAC inhibitor, increased the cisplatin sensitivity
      of several NSCLC cell lines with low ERCC1 expression but not those with high
      ERCC1 expression or gain-of-function (GOF) p53 mutation despite of ERCC1
      expression level. ERCC1 knockdown increased the cisplatin sensitivity of NSCLC
      cell lines with high ERCC1 expression without GOF p53 mutations. In addition, in
      low ERCC1 expression NSCLC cell lines, knockdown of GOF mutant p53 enhanced
      cisplatin sensitivity. Further double knockdown of ERCC1 and GOF mutant p53 but
      not ERCC1 knockdown alone increased the cisplatin sensitivity of cells with both
      high ERCC1 expression and GOF p53 mutations. Therefore, this study demonstrated
      that ERCC1 expression combined with p53 mutation status may determine the
      efficacy of cisplatin and HDACi combined therapy and guide the development of
      future NSCLC therapies. 

PMID- 25944618
TI  - OVOL guides the epithelial-hybrid-mesenchymal transition.
AB  - Metastasis involves multiple cycles of Epithelial-to-Mesenchymal Transition (EMT)
      and its reverse-MET. Cells can also undergo partial transitions to attain a
      hybrid epithelial/mesenchymal (E/M) phenotype that has maximum cellular
      plasticity and allows migration of Circulating Tumor Cells (CTCs) as a cluster.
      Hence, deciphering the molecular players helping to maintain the hybrid E/M
      phenotype may inform anti-metastasis strategies. Here, we devised a mechanism
      based mathematical model to couple the transcription factor OVOL with the core
      EMT regulatory network miR-200/ZEB that acts as a three-way switch between the E,
      E/M and M phenotypes. We show that OVOL can modulate cellular plasticity in
      multiple ways - restricting EMT, driving MET, expanding the existence of the
      hybrid E/M phenotype and turning both EMT and MET into two-step processes. Our
      theoretical framework explains the differences between the observed effects of
      OVOL in breast and prostate cancer, and provides a platform for investigating
      additional signals during metastasis. 

PMID- 25944619
TI  - Epithelial to mesenchymal transition is associated with rapamycin resistance.
AB  - Rapamycin analogues have antitumor efficacy in several tumor types, however few
      patients demonstrate tumor regression. Thus, there is a pressing need for markers
      of intrinsic response/resistance and rational combination therapies. We
      hypothesized that epithelial-to-mesenchymal transition (EMT) confers rapamycin
      resistance. We found that the epithelial marker E-cadherin protein is higher in
      rapamycin sensitive (RS) cells and mesenchymal breast cancer cell lines selected
      by transcriptional EMT signatures are less sensitive to rapamycin. MCF7 cells,
      transfected with constitutively active mutant Snail, had increased rapamycin
      resistance (RR) compared to cells transfected with wild-type Snail. Conversely,
      we transfected two RR mesenchymal cell lines-ACHN and MDA-MB-231-with miR-200b/c
      or ZEB1 siRNA to promote mesenchymal-to-epithelial transition. This induced E
      cadherin expression in both cell lines, and ACHN demonstrated a significant
      increase in RS. Treatment of ACHN and MDA-MB-231 with trametinib modulated EMT in
      ACHN cells in vitro. Treatment of MDA-MB-231 and ACHN xenografts with trametinib
      in combination with rapamycin resulted in significant growth inhibition in both
      but without an apparent effect on EMT. Future studies are needed to determine
      whether EMT status is predictive of sensitivity to rapalogs and to determine
      whether combination therapy with EMT modulating agents can enhance antitumor
      effects of PI3K/mTOR inhibitors. 

PMID- 25944620
TI  - HOXB13 and ALX4 induce SLUG expression for the promotion of EMT and cell invasion
      in ovarian cancer cells.
AB  - Homeoproteins, a family of transcription factors that have conserved homeobox
      domains, play critical roles in embryonic development in a wide range of species.
      Accumulating studies have revealed that homeoproteins are aberrantly expressed in
      multiple tumors and function as either tumor promoters or suppressors. In this
      study, we show that two homeoproteins, HOXB13 and ALX4, are associated with
      epithelial to mesenchymal transition (EMT) and invasion of ovarian cancer cells.
      HOXB13 and ALX4 formed a complex in cells, and exogenous expression of either
      protein promoted EMT and invasion. Conversely, depletion of either protein
      suppressed invasion and induced reversion of EMT. SLUG is a C2H2-type zinc-finger
      transcription factor that promotes EMT in various cell lines. Knockdown of HOXB13
      or ALX4 suppressed SLUG expression, and exogenous expression of either protein
      promoted SLUG expression. Finally, we showed that SLUG expression was essential
      for the HOXB13- or ALX4-mediated EMT and invasion. Our results show that
      HOXB13/SLUG and ALX4/SLUG axes are novel pathways that promote EMT and invasion
      of ovarian cancer cells. 

PMID- 25944622
TI  - p.Leu636Pro mutation is associated with cystic fibrosis transmembrane conductance
      regulator-related disorders (congenital bilateral absence of vas deferens).

PMID- 25944623
TI  - Potent and long-term antiangiogenic efficacy mediated by FP3-expressing oncolytic
      adenovirus.
AB  - Various ways to inhibit vascular endothelial growth factor (VEGF), a key
      facilitator in tumor angiogenesis, are being developed to treat cancer. The
      soluble VEGF decoy receptor (FP3), due to its high affinity to VEGF, is a highly
      effective and promising strategy to disrupt VEGF signaling pathway. Despite
      potential advantage and potent therapeutic efficacy, its employment has been
      limited by very poor in vivo pharmacokinetic properties. To address this
      challenge, we designed a novel oncolytic adenovirus (Ad) expressing FP3
      (RdB/FP3). To demonstrate the VEGF-specific nature of RdB/FP3, replication
      incompetent Ad expressing FP3 (dE1/FP3) was also generated. dE1/FP3 was highly
      effective in reducing VEGF expression and functionally elicited an
      antiangiogeneic effect. Furthermore, RdB/FP3 exhibited a potent antitumor effect
      compared with RdB or recombinant FP3. Consistent with these data, RdB/FP3 was
      shown to greatly decrease VEGF expression level and vessel density and increase
      apoptosis in both tumor endothelial and tumor cells, verifying potent suppressive
      effects of RdB/FP3 on VEGF-mediated tumor angiogenesis in vivo. Importantly, the
      therapeutic mechanism of antitumor effect mediated by RdB/FP3 is associated with
      prolonged VEGF silencing efficacy and enhanced oncolysis via cancer cell-specific
      replication of oncolytic Ad. Taken together, RdB/FP3 provides a new promising
      therapeutic approach in the treatment of cancer and angiogenesis-related
      diseases. 

PMID- 25944621
TI  - A simplified interventional mapping system (SIMS) for the selection of
      combinations of targeted treatments in non-small cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) is a leading cause of death worldwide.
      Targeted monotherapies produce high regression rates, albeit for limited patient
      subgroups, who inevitably succumb. We present a novel strategy for identifying
      customized combinations of triplets of targeted agents, utilizing a simplified
      interventional mapping system (SIMS) that merges knowledge about existent drugs
      and their impact on the hallmarks of cancer. Based on interrogation of matched
      lung tumor and normal tissue using targeted genomic sequencing, copy number
      variation, transcriptomics, and miRNA expression, the activation status of 24
      interventional nodes was elucidated. An algorithm was developed to create a
      scoring system that enables ranking of the activated interventional nodes for
      each patient. Based on the trends of co-activation at interventional points,
      combinations of drug triplets were defined in order to overcome resistance. This
      methodology will inform a prospective trial to be conducted by the WIN
      consortium, aiming to significantly impact survival in metastatic NSCLC and other
      malignancies. 

PMID- 25944624
TI  - Multidisciplinary, Nurse-Led Psychiatric Consultation in Nursing Homes: A Pilot
      Study in Clinical Practice.
AB  - PURPOSE: To determine the effects of multidisciplinary, nurse-led psychiatric
      consultation on behavioral problems of nursing home residents. Residents often
      suffer from psychiatric symptoms, while staff psychiatric expertise varies.
      DESIGN AND METHODS: A pre-post study was conducted in seven homes using the
      Neuropsychiatric Inventory Nursing Home version (NPI-NH). FINDINGS: In 71
      consultations during 18 months, 56-75% of residents suffered from
      agitation/aggression, depression, anxiety, and disinhibition. Post-intervention
      (n = 54), frequency, and severity of psychiatric symptoms were significantly and
      clinically meaningfully reduced. Also, staff suffered from less work stress.
      PRACTICE IMPLICATIONS: Nurse-led psychiatric consultation is valuable to both
      nursing home residents and staff.

PMID- 25944625
TI  - Characterizing mobility from the prosthetic limb user's perspective: Use of focus
      groups to guide development of the Prosthetic Limb Users Survey of Mobility.
AB  - BACKGROUND: Input from target respondents in the development of patient-reported
      outcome measures is necessary to ensure that the instrument is meaningful.
      OBJECTIVES: To solicit perspectives of prosthetic limb users about their mobility
      experiences and to inform development of the Prosthetic Limb Users Survey of
      Mobility. STUDY DESIGN: Qualitative study. METHODS: Four focus groups of lower
      limb prosthesis users were held in different regions of the United States. Focus
      group transcripts were coded, and themes were identified. Feedback from
      participants was used to develop a framework for measuring mobility with a lower
      limb prosthesis. RESULTS: Focus group participants (N = 37) described mobility as
      a confluence of factors that included characteristics of the individual,
      activity, and environment. Identified themes were defined as individual
      characteristics, forms of movement, and environmental situations. Prosthetic
      mobility was conceptualized as movement activities performed in an environmental
      or situational context. CONCLUSION: Respondent feedback used to guide development
      of Prosthetic Limb Users Survey of Mobility established a foundation for a new
      person-centered measure of mobility with a prosthetic limb. CLINICAL RELEVANCE:
      Perspectives of target respondents are needed to guide development of instruments
      intended to measure health outcomes. Focus groups of prosthetic limb users were
      conducted to solicit experiences related to mobility with a lower limb
      prosthesis. Results were used to inform development of a clinically meaningful,
      person-centered instrument.

PMID- 25944626
TI  - Sialic Acid Hydroxamate: A Potential Antioxidant and Inhibitor of Metal-Induced
      beta-Amyloid Aggregates.
AB  - Current methods for Alzheimer's treatment require a three-component system: metal
      chelators, antioxidants, and amyloid beta (Abeta)-peptide-binding scaffolds. We
      report sialic acid (Sia) hydroxamate as a potential radical scavenger and metal
      chelator to inhibit Abeta aggregation. A cell viability assay revealed that Sia
      hydroxamate can protect HeLa and glioblastoma (LN229) cells from oxidative damage
      induced by the Fenton reaction. Sedimentation and turbidity assays showed
      profound protection of neuroblastoma SH-SY5Y cells from metal-induced Abeta
      aggregation and neural toxicity. 

PMID- 25944627
TI  - American Psychological Association colluded with US officials to bolster CIA
      torture program, report alleges.

PMID- 25944628
TI  - Insulin Resistance and Risk of Cardiovascular Disease in Postmenopausal Women: A
      Cohort Study From the Women's Health Initiative.
AB  - BACKGROUND: Insulin resistance is associated with diabetes mellitus, but it is
      uncertain whether it improves cardiovascular disease (CVD) risk prediction beyond
      traditional cardiovascular risk factors. METHODS AND RESULTS: We identified
      15,288 women from the Women's Health Initiative Biomarkers studies with no
      history of CVD, atrial fibrillation, or diabetes mellitus at baseline (1993
      1998). We assessed the prognostic value of adding fasting serum insulin, HOMA-IR
      (homeostasis model assessment-insulin resistance), serum-triglyceride-to-serum
      high-density lipoprotein-cholesterol ratio TG/HDL-C, or impaired fasting glucose
      (serum glucose >=110 mg/dL) to traditional risk factors in separate Cox
      multivariable analyses and assessed risk discrimination and reclassification. The
      study end point was major CVD events (nonfatal and fatal coronary heart disease
      and ischemic stroke) within 10 years, which occurred in 894 (5.8%) women. Insulin
      resistance was associated with CVD risk after adjusting for age and
      race/ethnicity with hazard ratios (95% confidence interval [CI]) per doubling in
      insulin of 1.21 (CI, 1.12-1.31), in HOMA-IR of 1.19 (CI, 1.11-1.28), in TG/HDL-C
      of 1.35 (CI, 1.26-1.45), and for impaired fasting glucose of 1.31 (CI, 1.05
      1.64). Although insulin, HOMA-IR, and TG/HDL-C remained associated with increased
      CVD risk after adjusting for most CVD risk factors, none remained significant
      after adjusting for HDL-C: hazard ratios for insulin, 1.06 (CI, 0.98-1.16); for
      HOMA-IR, 1.06 (CI, 0.98-1.15); for TG/HDL-C, 1.11 (CI, 0.99-1.25); and for
      glucose, 1.20 (CI, 0.96-1.50). Insulin resistance measures did not improve CVD
      risk discrimination and reclassification. CONCLUSIONS: Measures of insulin
      resistance were no longer associated with CVD risk after adjustment for high
      density lipoprotein-cholesterol and did not provide independent prognostic
      information in postmenopausal women without diabetes mellitus. CLINICAL TRIAL
      REGISTRATION INFORMATION: URL: http://www.clinicaltrial.gov. Unique identifier:
      NCT00000611.

PMID- 25944629
TI  - Patients' and providers' perspectives of a polypill strategy to improve
      cardiovascular prevention in Australian primary health care: a qualitative study
      set within a pragmatic randomized, controlled trial.
AB  - BACKGROUND: This study explores health provider and patient attitudes toward the
      use of a cardiovascular polypill as a health service strategy to improve
      cardiovascular prevention. METHODS AND RESULTS: In-depth, semistructured
      interviews (n=94) were conducted with health providers and patients from
      Australian general practice, Aboriginal community-controlled and government-run
      Indigenous Health Services participating in a pragmatic randomized controlled
      trial evaluating a polypill-based strategy for high-risk primary and secondary
      cardiovascular disease prevention. Interview topics included polypill strategy
      acceptability, factors affecting adherence, and trial implementation. Transcribed
      interview data were analyzed thematically and interpretively. Polypill patients
      commented frequently on cost-savings, ease, and convenience of a daily-dosing
      pill. Most providers considered a polypill strategy to facilitate improved
      patient medication use. Indigenous Health Services providers and indigenous
      patients thought the strategy acceptable and beneficial for indigenous patients
      given the high disease burden. Providers noted the inflexibility of the fixed
      dose regimen, with dosages sometimes inappropriate for patients with complex
      management considerations. Future polypill formulations with varied strengths and
      classes of medications may overcome this barrier. Many providers suggested the
      polypill strategy, in its current formulations, might be more suited to high-risk
      primary prevention patients. CONCLUSIONS: The polypill strategy was generally
      acceptable to patients and providers in cardiovascular prevention. Limitations to
      provider acceptability of this particular polypill were revealed, as was a
      perception it might be more suitable for high-risk primary prevention patients,
      though future combinations could facilitate its use in secondary prevention.
      Participants suggested a polypill-based strategy as particularly appropriate for
      lowering the high cardiovascular burden in indigenous populations. CLINICAL TRIAL
      REGISTRATION: URL: http://www.anzctr.org.au. ANZCTRN: 12608000583347.

PMID- 25944630
TI  - Challenge of change: incorporating family members in hospital care.

PMID- 25944631
TI  - Setting the stage for evidence-based medicine.

PMID- 25944632
TI  - Prognostic Implications of Level-of-Care at Tertiary Heart Centers Compared With
      Other Hospitals After Resuscitation From Out-of-Hospital Cardiac Arrest.
AB  - BACKGROUND: Studies have found higher survival rates after out-of-hospital
      cardiac arrest and admission to tertiary heart centers. The aim was to examine
      the level-of-care at tertiary centers compared with nontertiary hospitals and the
      association with outcome after out-of-hospital cardiac arrest. METHODS AND
      RESULTS: Consecutive out-of-hospital cardiac arrest patients (n=1078) without ST
      segment-elevation myocardial infarction admitted to tertiary centers (54%) and
      nontertiary hospitals (46%) were included (2002-2011). Patient charts were
      reviewed focusing on level-of-care and comorbidity. Survival to discharge
      differed significantly with 45% versus 24% of patients discharged alive
      (P<0.001), and after adjustment for prognostic factors admissions to tertiary
      centers were still associated with lower 30-day mortality (hazard ratio, 0.78
      [0.64-0.96; P=0.02]), independent of comorbidity. The adjusted odds of predefined
      markers of level-of-care were higher in tertiary centers: admission to intensive
      care unit (odds ratio [OR], 1.8 [95% confidence interval, 1.2-2.5]), temporary
      pacemaker (OR, 6.4 [2.2-19]), vasoactive agents (OR, 1.5 [1.1-2.1]), acute (<24
      hours) and late coronary angiography (OR, 10 [5.3-22] and 3.8 [2.5-5.7]),
      neurophysiological examination (OR, 1.8 [1.3-2.6]), and brain computed tomography
      (OR, 1.9 [1.4-2.6]), whereas no difference in therapeutic hypothermia was noted.
      Patients at tertiary centers were more often consulted by a cardiologist (OR, 8.6
      [5.0-15]), had an echocardiography (OR, 2.8 [2.1-3.7]), and survivors more often
      had implantable cardioverter defibrillator's implanted (OR, 2.1 [1.2-3.6]).
      CONCLUSIONS: Admissions to tertiary centers were associated with significantly
      higher survival after out-of-hospital cardiac arrest in patients without ST
      segment-elevation myocardial infarction in the Copenhagen area even after
      adjustment for prognostic factors including comorbidity. Level-of-care seems
      higher in tertiary centers both in the early phase, during the intensive care
      unit admission, and in the workup before discharge. The varying level-of-care may
      contribute to the survival difference; however, differences in comorbidity do not
      seem to matter significantly.

PMID- 25944633
TI  - Long-term cost-effectiveness of providing full coverage for preventive
      medications after myocardial infarction.
AB  - BACKGROUND: Adherence to drugs that are prescribed after myocardial infarction
      remains suboptimal. Although eliminating patient cost sharing for secondary
      prevention increases adherence and reduces rates of major cardiovascular events,
      the long-term clinical and economic implications of this approach have not been
      adequately evaluated. METHODS AND RESULTS: We developed a Markov model simulating
      a hypothetical cohort of commercially insured patients who were discharged from
      the hospital after myocardial infarction. Patients received beta-blockers, renin
      angiotensin system antagonists, and statins without cost sharing (full coverage)
      or at the current level of insurance coverage (usual coverage). Model inputs were
      extracted from the Post Myocardial Infarction Free Rx Event and Economic
      Evaluation trial and other published literature. The main outcome was an
      incremental cost-effectiveness ratio as measured by cost per quality-adjusted
      life year gained. Patients receiving usual coverage lived an average of 9.46
      quality-adjusted life years after their event and incurred costs of $171,412.
      Patients receiving full coverage lived an average of 9.60 quality-adjusted life
      years and incurred costs of $167,401. Compared with usual coverage, full coverage
      would result in greater quality-adjusted survival (0.14 quality-adjusted life
      years) and less resource use ($4011) per patient. Our results were sensitive to
      alterations in the risk reduction for post-myocardial infarction events from full
      coverage. CONCLUSIONS: Providing full prescription drug coverage for evidence
      based pharmacotherapy to commercially insured post-myocardial infarction patients
      has the potential to improve health outcomes and save money from the societal
      perspective over the long-term. CLINICAL TRIAL REGISTRATION INFORMATION:
      https://www.clinicaltrials.gov. Unique identifier: NCT00566774.

PMID- 25944634
TI  - Increasing serum transferrin to reduce tissue iron overload due to ineffective
      erythropoiesis.

PMID- 25944635
TI  - Jekyll and Hyde: the role of heme oxygenase-1 in erythroid biology.

PMID- 25944636
TI  - Personalized medicine in myelodysplastic syndromes: wishful thinking or already
      clinical reality?

PMID- 25944637
TI  - Aging and malignant hemopathies.

PMID- 25944638
TI  - Confounding effect of cyclosporine dosing when comparing horse and rabbit
      antithymocyte globulin in patients with severe aplastic anemia.

PMID- 25944639
TI  - Answer to "Confounding effect of cyclosporine dosing when comparing horse and
      rabbit antithymocyte globulin in patients with severe aplastic anemia".

PMID- 25944641
TI  - Insect proteins-a new source for animal feed: The use of insect larvae to recycle
      food waste in high-quality protein for livestock and aquaculture feeds is held
      back largely owing to regulatory hurdles.

PMID- 25944640
TI  - On the safety of intravenous iron, evidence trumps conjecture.

PMID- 25944642
TI  - Ancient DNA sheds light on the ancestry of pre-hispanic Canarian pigs.
AB  - BACKGROUND: Canarian Black (CB) pigs belong to an autochthonous and endangered
      breed, which is spread throughout the Canarian archipelago. It is commonly
      accepted that they represent a relic of the pig populations that were bred by the
      Berbers in North Africa over millennia. It is important to note that the
      geographic isolation of the Canary Islands has preserved this genetic legacy
      intact from foreign introgressions until the Spanish conquest of the archipelago
      in the 15(th) century. Ten years ago, it was demonstrated that, in CB pigs, the
      frequency of the Asian A2 cytochrome-b haplogroup reached 73%. The current work
      aimed at investigating whether this observation is explained by either a recent
      or an ancient introgression of CB pigs with Far Eastern pigs. RESULTS: Genetic
      analyses of 23 ancient samples from pre-hispanic Canarian pigs (420 to 2500 years
      before present) showed that Near Eastern and Far Eastern genetic signatures were
      totally absent in the primitive Canarian pre-hispanic pigs. Indeed, the
      haplotypes detected in these pigs were closely related to those of North African
      and European wild boars. CONCLUSIONS: Our results demonstrate that the high
      frequency of the Far Eastern mitochondrial cytochrome B A2 haplotype in modern
      Canarian Black pigs probably corresponds to a relatively recent introgression
      with British breeds.

PMID- 25944643
TI  - Utilizing immunoaffinity chromatography (IAC) cross-reactivity in GC-MS/MS
      exemplified at the measurement of prostaglandin E1 in human plasma using
      prostaglandin E2-specific IAC columns.
AB  - Immunoaffinity chromatography (IAC) is an elegant and highly efficient method to
      isolate a particular compound from biological samples for measurement by mass
      spectrometry coupled to GC, CE, or LC. The utility of IAC for the quantitative
      determination of several prostaglandins including prostaglandin E2 (PGE2) by GC
      MS/MS and LC-MS/MS has been demonstrated. The aim of the present work was to test
      whether the cross-reactivity of the antibody immobilized on an insoluble support
      can be utilized for the quantitative determination of biomolecules by stable
      isotope dilution mass spectrometry. In this communication, we provide evidence
      that this is indeed possible for prostaglandin E1 (PGE1) in human plasma by GC
      MS/MS using commercially available Sepharose 4-based IAC columns with immobilized
      mouse anti-PGE2 monoclonal antibody with a declared cross-reactivity of about 19%
      toward PGE1. Endogenous PGE1 and the internal standard [3,3',4,4'-(2)H4]-PGE1 (d4
      PGE1) externally added to human plasma samples were extracted by IAC, converted
      to their pentafluorobenzyl ester-methoxime-trimethylsilyl ether derivatives and
      analyzed by GC-MS/MS in the electron-capture negative-ion chemical ionization
      mode. Quantification was performed by selected-reaction monitoring of the mass
      transition m/z 526->m/z 258 for PGE1 and m/z 530->m/z 262 for d4-PGE1. By this
      method we measured PGE1 concentrations in EDTA plasma samples (1mL) of six
      healthy volunteers in the range 10-25pg/mL (29-72pM). PGE1 plasma concentration
      showed a trend for positive correlation with plasma parameters such as low
      density lipoprotein (LDL)-cholesterol, total cholesterol and glucose. The method
      described here provides a novel tool to study the potential link of PGE1
      formation to dyslipidemia, insulin resistance and related metabolic disorders. 

PMID- 25944645
TI  - Presence of macronodules in thoracic sarcoidosis: prevalence and computed
      tomographic findings.
AB  - AIM: To assess the prevalence and radiological findings of macronodules in
      patients with thoracic sarcoidosis. MATERIALS AND METHODS: Data was collected
      regarding 226 patients with pathologically proven thoracic sarcoidosis. Among
      them, macronodules defined as well-defined nodules greater than 5 mm were found
      in 58 patients. The macronodules were evaluated by their number, size, margin,
      shape, lobar location, distance from the pleura, and temporal change. Patients
      were classified into two groups, patients with macronodules (n = 58) and without
      macronodules (n = 168). The level of serum angiotensin-converting enzyme (ACE),
      systemic involvement, and the maximum standardized uptake value (maxSUV) on (18)F
      fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) in both groups
      were then compared. RESULTS: A total of 216 macronodules were identified in 58
      patients. The mean number of macronodules per patient was 3.3, and the mean size
      was 6.3 mm. Most of the macronodules were located in lower lobes (63.4%) and
      showed round-to-ovoid (95.8%) shape. The mean distance from the pleura was 5 mm.
      In 76% of the 63 nodules that were followed using CT scanning, any interval
      changes in size was also accompanied by the same change in mediastinal
      lymphadenopathy. On comparison of the two groups, the presence of
      lymphadenopathy, parenchymal involvement, and the maxSUV of thoracic
      lymphadenopathy were shown to be statistically different. CONCLUSION: Well
      defined macronodules greater than 5 mm were not uncommonly seen in patients with
      thoracic sarcoidosis. The macronodules are usually located in the lower lobes
      near the pleura, and the interval changes in mediastinal lymphadenopathy may be
      associated with similar changes in the size of nodules.

PMID- 25944646
TI  - First-Time Mothers with a History of Infertility: Their Internalized Pressure to
      Breastfeed.
AB  - BACKGROUND: The meaning of breastfeeding and breastfeeding experiences has been
      studied extensively in general and specific populations. However, there is little
      research about the meaning of breastfeeding and breastfeeding experiences in
      first-time mothers who were previously infertile. OBJECTIVE: This article aims to
      understand the breastfeeding experiences of new mothers with a history of
      infertility. METHODS: Twelve women who were first-time mothers and conceived
      their infants through fertility treatments were interviewed about their early
      postpartum experiences as part of a larger phenomenological study. Interview
      transcripts were reviewed, and data about breastfeeding were extracted and
      analyzed using thematic analysis. RESULTS: One main theme from the breastfeeding
      data emerged, "Internalized Pressure to Breastfeed," with 3 subthemes: "My Only
      Chance to Breastfeed," "The One Natural Thing I Should Be Able to Do," and "Not
      Breastfeeding Means Failing at Motherhood." New mothers who have undergone
      fertility treatment equated breastfeeding with being the perfect mother and
      attached special meanings to the act of breastfeeding. CONCLUSION: This study
      demonstrated that mothers who were previously infertile have unique breastfeeding
      experiences. Health care professionals need to be sensitized to these women's
      internalized pressure to breastfeed. Additional research is needed to fully
      explore the breastfeeding experiences of this group of women.

PMID- 25944644
TI  - Mast Cell Activation Syndrome.
AB  - Mast cell activation syndrome (MCAS) involves the skin, gastrointestinal,
      cardiovascular, respiratory, and neurologic systems, classified as primary,
      secondary, and idiopathic. Earlier criteria for MCAS diagnosis included episodic
      symptoms with mast cell mediators affecting two or more organ systems with
      urticaria, angioedema, flushing, nausea, vomiting, diarrhea, abdominal cramping,
      hypotensive syncope, tachycardia, wheezing, conjunctival injection, pruritus,
      nasal stuffiness, decrease in frequency, severity, or resolution of symptoms with
      anti-mediator therapy including H1/H2 receptor antagonists, anti-leukotrienes, or
      mast cell stabilizers. Laboratory data includes an increased validated urinary or
      serum markers of MCAS, documentation of an increase of the marker above the
      patient's baseline value during symptomatic periods on more than two occasions,
      or baseline serum tryptase levels that are persistently above 15 ng/mL.
      Laboratory data also includes an increase of the tryptase level above baseline
      value on one occasion. Other assays are 24-h urine histamine metabolites, PGD2 or
      its metabolite, and 11-beta-prostaglandin F2 alpha. A recent global
      classification is a response of clinical symptoms, a substantial transient
      increase in serum total tryptase or increase in other mast cell-derived
      mediators, histamine or PGD2 or urinary metabolites, and agents that attenuate
      production or mast cell mediator activities. "Spectrum of MCAS disorders" has
      been proposed, highlighting symptoms' diagnostic tests and treatments.

PMID- 25944647
TI  - Validation of the Arabic Version of the Iowa Infant Feeding Attitude Scale among
      Lebanese Women.
AB  - BACKGROUND: There is need in the Arab world for validated instruments that can
      reliably assess infant feeding attitudes among women. The 17-item Iowa Infant
      Feeding Attitude Scale (IIFAS) has consistently shown good reliability and
      validity in different cultures and the ability to predict breastfeeding intention
      and exclusivity. OBJECTIVE: This study assessed the psychometric properties of
      the Arabic version of the IIFAS (IIFAS-A). METHODS: After translating to
      classical Arabic and back-translating to English, the IIFAS-A was pilot tested
      among 20 women for comprehension, clarity, length, and cultural appropriateness.
      The IIFAS-A was then validated among 170 women enrolled in a breastfeeding
      promotion and support clinical trial in Lebanon. RESULTS: The IIFAS-A showed
      acceptable internal consistency reliability (Cronbach's alpha = 0.640), with
      principal components analysis revealing that it is unidimensional. The 17 items
      had good interitem reliabilities ranging between 0.599 and 0.665. The number of
      breastfed children was the only predictor of the overall IIFAS-A score in a
      multivariate stepwise regression model (beta = 1.531, P < .0001). CONCLUSION: The
      17-item IIFAS-A is a reliable and valid instrument for measuring women's infant
      feeding attitudes in the Arab context.

PMID- 25944648
TI  - International normalized ratio stability in warfarin-experienced patients with
      nonvalvular atrial fibrillation.
AB  - BACKGROUND: Maintaining stable levels of anticoagulation using warfarin therapy
      is challenging. Few studies have examined the stability of the international
      normalized ratio (INR) in patients with nonvalvular atrial fibrillation (NVAF)
      who have had >=6 months' exposure to warfarin anticoagulation for stroke
      prevention. OBJECTIVE: Our objective was to describe INR control in NVAF patients
      who had been receiving warfarin for at least 6 months. METHODS: Using
      retrospective patient data from the CoagClinicTM database, we analyzed data from
      NVAF patients treated with warfarin to assess the quality of INR control and
      possible predictors of poor INR control. Time within, above, and below the
      recommended INR range (2.0-3.0) was calculated for patients who had received
      warfarin for >=6 months and had three or more INR values. The analysis also
      assessed INR patterns and resource utilization of patients with an INR >4.0.
      Logistic regression models were used to determine factors associated with poor
      INR control. RESULTS: Patients (n = 9433) had an average of 1.6 measurements per
      30 days. Mean follow-up time was 544 days. Approximately 39% of INR values were
      out of range, with 23% of INR values being <2.0 and 16% being >3.0. Mean percent
      time with INR in therapeutic range was 67%; INR <2.0 was 19% and INR >3.0 was
      14%. Patients with more than one reading of INR >4.0 (~39%) required an average
      of one more visit and took 3 weeks to return to an in-range INR. Male sex and age
      >75 years were predictive of better INR control, whereas a history of heart
      failure or diabetes were predictive of out-of-range INR values. However, patient
      characteristics did not predict the likelihood of INR >4.0. CONCLUSIONS: Out-of
      range INR values remain frequent in patients with NVAF treated with warfarin.
      Exposure to high INR values was common, resulting in increased resource
      utilization.

PMID- 25944649
TI  - Reduced erythrocyte susceptibility and increased host clearance of young
      parasites slows Plasmodium growth in a murine model of severe malaria.
AB  - The best correlate of malaria severity in human Plasmodium falciparum (Pf)
      infection is the total parasite load. Pf-infected humans could control parasite
      loads by two mechanisms, either decreasing parasite multiplication, or increasing
      parasite clearance. However, few studies have directly measured these two
      mechanisms in vivo. Here, we have directly quantified host clearance of parasites
      during Plasmodium infection in mice. We transferred labelled red blood cells
      (RBCs) from Plasmodium infected donors into uninfected and infected recipients,
      and tracked the fate of donor parasites by frequent blood sampling. We then
      applied age-based mathematical models to characterise parasite clearance in the
      recipient mice. Our analyses revealed an increased clearance of parasites in
      infected animals, particularly parasites of a younger developmental stage.
      However, the major decrease in parasite multiplication in infected mice was not
      mediated by increased clearance alone, but was accompanied by a significant
      reduction in the susceptibility of RBCs to parasitisation. 

PMID- 25944650
TI  - Species Diversity and Pheno- and Genotypic Antibiotic Resistance Patterns of
      Staphylococci Isolated from Retail Ground Meats.
AB  - The presence and species diversity of staphylococci in 250 ground beef and lamb
      meat samples obtained from Diyarbakir, Turkey were investigated. The presence of
      the 16S rRNA gene, mecA, nuc, pvl, and femA was analyzed by multiplex PCR. Pheno-
      and genotypic antibiotic resistance profiles of 208 staphylococci isolates were
      established. Of the ground beef and ground lamb samples, 86.4% and 62.4% were
      positive for staphylococci, respectively. Staphylococcus aureus, S.
      saprophyticus, S. hominis, S. lentus, S. pasteuri, S. warneri, S. intermedius,
      and S. vitulinus made up 40.8%, 28.8%, 11%, 3.8%, 3.8%, 2.4%, 2.4%, and 2.4% of
      isolates, respectively. Of the 85 S. aureus isolates, 40%, 47%, and 5.8% carried
      femA, mecA, and pvl, respectively, whereas the corresponding rates for the 118
      coagulase-negative staphylococci (CoNS) were 0%, 10.1%, and 0%, respectively. We
      determined from the 208 isolates, the highest antibiotic resistances were to
      tetracycline and oxytetracycline (85.5%), followed by penicillin (51.4%),
      novobiocin (45.6%), ampicillin (39.9%), and doxycycline (31.7%), using the
      Clinical and Laboratory Standards Inst. (CLSI) method. All isolates were
      sensitive to gentamycin, ofloxacin, and tobramycin, but 2.3% of the S. aureus
      isolates had resistance to vancomycin. The staphylococci isolates carried tet(K),
      blaZ, tet(L), tet(W), cat, tet(S), tet(M), ermB, ermA, and ermC antibiotic
      resistance genes at rates of 59%, 51.7%, 36.9%, 31.8%, 27.2%, 27.2%, 24.4%,
      18.1%, 7.9%, and 3.9%, respectively. 

PMID- 25944651
TI  - Elevated GAPDH expression is associated with the proliferation and invasion of
      lung and esophageal squamous cell carcinomas.
AB  - Glyceraldehyde-3-phosphate dehydrogenase, is one of the most investigated
      housekeeping genes and widely used as an internal control in analysis of gene
      expression levels. The present study was designed to assess whether GAPDH is
      associated with cancer cell growth and progression and, therefore may not be a
      good internal control in cancer research. Our results from clinical tissue
      studies showed that the levels of GAPDH protein were significantly up-regulated
      in lung squamous cell carcinoma tissues, compared with the adjacent normal lung
      tissues, and this was confirmed by western blotting and immunohistochemistry.
      GAPDH knockdown by siRNA resulted in significant reductions in proliferation,
      migration, and invasion of lung squamous carcinoma cells in vitro. In a nude
      mouse cancer xenograft model, GAPDH knockdown significantly inhibited the cell
      proliferation and migration/invasion in vivo. In summary, GAPDH may not be an
      appropriate internal control for gene expression studies, especially in cancer
      research. The role of GAPDH in cancer development and progression should be
      further examined in pre-clinical and clinical studies. 

PMID- 25944652
TI  - Characterisation of Chlamydia pneumoniae and other novel chlamydial infections in
      captive snakes.
AB  - Chlamydiosis has been described in both free-ranging and captive reptiles. The
      infection usually manifests as granulomatous inflammation in inner organs such as
      spleen, heart, lung and liver but might also occur in asymptomatic reptiles. The
      aim of this study was to investigate and characterise Chlamydia pneumoniae and
      potential other novel chlamydial infections in the choana and cloaca samples of
      137 clinically healthy captive snakes from six private collections. Forty eight
      samples from 29 animals were found to be positive by a Chlamydiaceae family
      specific qPCR. By Chlamydia species-specific ArrayTube Microarray, 43 samples
      were positive, with 36 of these being identified as C. pneumoniae. The prevalence
      of Chlamydia ranged from 5 to 33%. PCR and sequencing of the Chlamydiales 16S
      rRNA signature sequence of 21 Chlamydia positive samples revealed the presence of
      seven novel 16S rRNA genotypes. BLAST-n and phylogenetic analysis of the near
      full length 16S rRNA gene sequence of each of these novel 16S rRNA sequences
      revealed that five genotypes share closest sequence identity to 16S rRNA
      sequences from C. pneumoniae (98.6-99.2%), suggesting that these sequences are
      novel C. pneumoniae strains. One genotype is 96.9% similar to C. pneumoniae
      strains suggesting it may originate from a yet undescribed chlamydial species
      within the genus Chlamydia. This study further highlights the broad host range
      for C. pneumoniae and suggests that reptiles may still contain a significant and
      largely uncharacterised level of chlamydial genetic diversity that requires
      further investigation. 

PMID- 25944653
TI  - Diagnostic, prognostic and predictive relevance of molecular markers in gliomas.
AB  - The advances of genome-wide 'discovery platforms' and the increasing
      affordability of the analysis of significant sample sizes have led to the
      identification of novel mutations in brain tumours that became diagnostically and
      prognostically relevant. The development of mutation-specific antibodies has
      facilitated the introduction of these convenient biomarkers into most
      neuropathology laboratories and has changed our approach to brain tumour
      diagnostics. However, tissue diagnosis will remain an essential first step for
      the correct stratification for subsequent molecular tests, and the combined
      interpretation of the molecular and tissue diagnosis ideally remains with the
      neuropathologist. This overview will help our understanding of the pathobiology
      of common intrinsic brain tumours in adults and help guiding which molecular
      tests can supplement and refine the tissue diagnosis of the most common adult
      intrinsic brain tumours. This article will discuss the relevance of 1p/19q
      codeletions, IDH1/2 mutations, BRAF V600E and BRAF fusion mutations, more
      recently discovered mutations in ATRX, H3F3A, TERT, CIC and FUBP1, for diagnosis,
      prognostication and predictive testing. In a tumour-specific topic, the role of
      mitogen-activated protein kinase pathway mutations in the pathogenesis of
      pilocytic astrocytomas will be covered. 

PMID- 25944654
TI  - Effects of Uremic Toxins from the Gut Microbiota on Bone: A Brief Look at Chronic
      Kidney Disease.
AB  - Patients with chronic kidney disease (CKD) frequently have mineral and bone
      disorders (CKD-MBD) that are caused by several mechanisms. Recent research has
      suggested that uremic toxins from the gut such as p-cresyl sulfate (PCS) and
      indoxyl sulfate (IS) could also be involved in the development of bone disease in
      patients with CKD. IS and PCS are produced by microbiota in the gut, carried into
      the plasma bound to serum albumin, and are normally excreted into the urine.
      However, in patients with CKD, there is an accumulation of high levels of these
      uremic toxins. The exact mechanisms of action of uremic toxins in bone disease
      remain unclear. The purpose of this brief review is to discuss the link between
      uremic toxins (IS and PCS) and bone mineral disease in chronic kidney disease. 

PMID- 25944656
TI  - Laparoscopic implantation of neuromodulators for treating urinary dysfunctions
      and improving locomotion in multiple sclerosis patients.
AB  - INTRODUCTION AND HYPOTHESIS: The laparoscopic implantation of neuromodulation
      electrodes--the LION procedure--was first described as a rescue procedure in
      patients with local complications of a Brindley procedure. The objective of this
      video article is to demonstrate the technique for the laparoscopic implantation
      of electrodes for bilateral neuromodulation of femoral, sciatic and pudendal
      nerves and describe our initial experience with two multiple sclerosis (MS)
      patients. METHOD: This is a retrospective analysis of two patients with MS and
      neurogenic detrusor overactivity. A quadripolar electrode was implanted with two
      poles into the Alcock's canal and the two other laying over the lumbosacral
      trunk. The other two electrodes were implanted posteriorly to the femoral nerves.
      RESULTS: At the neuromodulation trial, both patients presented a full recovery of
      urinary symptoms. One of them found it easier to stand up for transfers and daily
      activities and the other managed to advance from the wheelchair to the walker and
      both patients received the permanent implant. At 1-year follow up, urinary
      results were maintained and 1 patient presented a disease relapse, demanding
      multiple reprogramming sessions. CONCLUSION: Our initial observations are
      encouraging and indicate that the LION procedure seems to produce in MS patients
      similar results to those observed in patients with spinal cord injury. Patients,
      however, should be advised that MS is a progressive disease and that the positive
      effects of neuromodulation can potentially fade with time and that multiple
      reprogramming sessions might be necessary.

PMID- 25944657
TI  - A vaginal mass and ulceration 8 years following Macroplastique(r) injection.

PMID- 25944658
TI  - How large does a rectocele have to be to cause symptoms? A 3D/4D ultrasound
      study.
AB  - INTRODUCTION: Rectocele is a common condition, which on imaging is defined by a
      pocket identified on Valsalva or defecation. Cut-offs of 10 and 20 mm for pocket
      depth have been described. This study analyses the correlation between rectocele
      depth and symptoms of bowel dysfunction to define a cut-off for the diagnosis of
      "significant rectocele" on ultrasound. METHODS: A retrospective study using 564
      archived data sets of patients seen at tertiary urogynaecological clinics.
      Patients underwent a standardised interview including a set of questions
      regarding bowel function, and translabial 3D/4D ultrasound. Assessments were
      undertaken supine and after voiding. Rectocele depth was measured on Valsalva.
      RESULTS: Out of 564, data on symptoms was missing in 18 and ultrasound volumes in
      25, leaving 521. Mean age was 56 years (range 18-86), mean BMI 29 (17-56).
      Presenting symptoms were prolapse (51 %), constipation (21 %), vaginal digitation
      (17 %), straining at stool (46 %), incomplete bowel emptying (41 %) and faecal
      incontinence (10 %). A clinically significant rectocele (ICS POPQ stage >=2) was
      found in 48 % (n=250). In 261 women a rectal diverticulum was identified, of an
      average depth of 17 (SD, 7) mm. On ROC statistics a cut- off of 15 mm in depth
      provided optimal sensitivities of 66 % for vaginal digitation and 63 % for
      incomplete emptying, and specificities of 52 and 57 % respectively. CONCLUSIONS:
      Rectocele depth is associated with symptoms of obstructed defecation. A
      "clinically significant" rectocele may be defined as a diverticulum of the rectal
      ampulla of >=15 mm in depth, although poor test characteristics limit clinical
      utility of this cut-off.

PMID- 25944659
TI  - Heterogeneity in post-intervention prolapse and urinary outcome reporting: a one
      year review of the International Urogynecology Journal.
AB  - INTRODUCTION: This review aimed to examine post-intervention prolapse,
      incontinence, and overactive bladder outcome measures published in the
      International Urogynecology Journal over the previous year and to report on the
      heterogeneity in outcome reporting. METHODS: All original article abstracts
      published in the print version of the International Urogynecology Journal in 2014
      were reviewed for possible inclusion. Those reporting on prolapse and/or
      incontinence and/or overactive bladder outcomes following a urogynecological
      intervention were analyzed. Articles were reviewed for all reported outcomes.
      Outcomes were categorized as primary or secondary and objective or subjective.
      RESULTS: Of 117 original articles published, 45 were reviewed. Among primary
      outcomes, 9 different outcomes were reported for prolapse and 11 for incontinence
      and overactive bladder. For prolapse, 6 different objective and 13 subjective
      outcomes were reported. For incontinence, 21 objective and 36 subjective outcomes
      were reported. Three different definitions were used for the outcome of "prolapse
      cure," 3 for "prolapse recurrence," and 4 for "stress incontinence cure." Several
      validated and non-validated questionnaires in addition to single unvalidated
      questions were used to measure subjective outcomes. CONCLUSIONS: This research
      highlights the diversity in outcome reporting for prolapse, incontinence, and
      overactive bladder after an intervention in the last year of publications alone.
      This can lead to serious challenges in the generation of higher order evidence,
      such as systematic reviews and meta-analyses. As a subspecialty, we need to aim
      for more cohesive reporting so as to allow for robust comparison and evidence
      dissemination.

PMID- 25944660
TI  - Regulatory O-GlcNAcylation sites on FoxO1 are yet to be identified.
AB  - O-GlcNAcylation is a reversible post-translational modification that regulates
      cytosolic and nuclear proteins. We and others previously demonstrated that FoxO1
      is O-GlcNAcylated in different cell types, resulting in an increase in its
      transcriptional activity. Four O-GlcNAcylation sites were identified in human
      FOXO1 but directed mutagenesis of each site individually had modest (T317) or no
      effect (S550, T648, S654) on its O-GlcNAcylation status and transcriptional
      activity. Moreover, the consequences of mutating all four sites had not been
      investigated. In the present work, we mutated these sites in the mouse Foxo1 and
      found that mutation of all four sites did not decrease Foxo1 O-GlcNAcylation
      status and transcriptional activity, and would even tend to increase them. In an
      attempt to identify other O-GlcNAcylation sites, we immunoprecipitated wild-type
      O-GlcNAcylated Foxo1 and analysed the tryptic digest peptides by mass
      spectrometry using High-energy Collisional Dissociation. We identified T646 as a
      new O-GlcNAcylation site on Foxo1. However, site directed mutagenesis of this
      site individually or together with all four previously identified residues did
      not impair Foxo1 O-GlcNAcylation and transcriptional activity. These results
      suggest that residues important for the control of Foxo1 activity by O
      GlcNAcylation still remain to be identified. 

PMID- 25944661
TI  - Chlamydia trachomatis inclusion membrane protein CT850 interacts with the dynein
      light chain DYNLT1 (Tctex1).
AB  - Chlamydia trachomatis actively subverts the minus-end directed microtubule motor,
      dynein, to traffic along microtubule tracks to the Microtubule Organizing Center
      (MTOC) where it remains within a membrane bound replicative vacuole for the
      duration of its intracellular development. Unlike most substrates of the dynein
      motor, disruption of the dynactin cargo-linking complex by over-expression of the
      p50 dynamitin subunit does not inhibit C. trachomatis transport. A requirement
      for chlamydial protein synthesis to initiate this process suggests that a
      chlamydial product supersedes a requirement for p50 dynamitin. A yeast 2-hybrid
      system was used to screen the chlamydia inclusion membrane protein CT850 against
      a HeLa cell cDNA library and identified an interaction with the dynein light
      chain DYNLT1 (Tctex1). This interaction was at least partially dependent upon an
      (R/K-R/K-X-X-R/K) motif that is characteristic of DYNLT1 binding domains. CT850
      expressed ectopically in HeLa cells localized at the MTOC and this localization
      is similarly dependent upon the predicted DYNLT1 binding domain. Furthermore,
      DYNLT1 is enriched at focal concentrations of CT850 on the chlamydial inclusion
      membrane that are known to interact with dynein and microtubules. Depletion of
      DYNLT1 disrupts the characteristic association of the inclusion membrane with
      centrosomes. Collectively, the results suggest that CT850 interacts with DYNLT1
      to promote appropriate positioning of the inclusion at the MTOC. 

PMID- 25944662
TI  - PPARgamma inhibits ovarian cancer cells proliferation through upregulation of miR
      125b.
AB  - miR-125b has essential roles in coordinating tumor proliferation, angiogenesis,
      invasiveness, metastasis and chemotherapy recurrence. In ovarian cancer miR-125b
      has been shown to be downregulated and acts as a tumor suppressor by targeting
      proto-oncogene BCL3. PPARgamma, a multiple functional transcription factor, has
      been reported to have anti-tumor effects through inhibition of proliferation and
      induction of differentiation and apoptosis by targeting the tumor related genes.
      However, it is unclear whether miR-125b is regulated by PPARgamma in ovarian
      cancer. In this study, we demonstrated that the miR-125b downregulated in ovarian
      cancer tissues and cell lines. Ligands-activated PPARgamma suppressed
      proliferation of ovarian cancer cells and this PPARgamma-induced growth
      inhibition is mediated by the upregulation of miR-125b. PPARgamma promoted the
      expression of miR-125b by directly binding to the responsive element in miR-125b
      gene promoter region. Thus, our results suggest that PPARgamma can induce growth
      suppression of ovarian cancer by upregulating miR-125b which inhibition of proto
      oncogene BCL3. These findings will extend our understanding of the function of
      PPARgamma in tumorigenesis and miR-125b may be a therapeutic intervention of
      ovarian cancer. 

PMID- 25944663
TI  - DNA METHYLTRANSFERASE 1 is involved in (m)CG and (m)CCG DNA methylation and is
      essential for sporophyte development in Physcomitrella patens.
AB  - DNA methylation has a crucial role in plant development regulating gene
      expression and silencing of transposable elements. Maintenance DNA methylation in
      plants occurs at symmetrical (m)CG and (m)CHG contexts ((m) = methylated) and is
      maintained by DNA METHYLTRANSFERASE 1 (MET1) and CHROMOMETHYLASE (CMT) DNA
      methyltransferase protein families, respectively. While angiosperm genomes encode
      for several members of MET1 and CMT families, the moss Physcomitrella patens,
      serving as a model for early divergent land plants, carries a single member of
      each family. To determine the function of P. patens PpMET we generated DeltaPpmet
      deletion mutant which lost (m)CG and unexpectedly (m)CCG methylation at loci
      tested. In order to evaluate the extent of (m)CCG methylation by MET1, we
      reexamined the Arabidopsis thaliana Atmet1 mutant methylome and found a similar
      pattern of methylation loss, suggesting that maintenance of DNA methylation by
      MET1 is conserved through land plant evolution. While DeltaPpmet displayed no
      phenotypic alterations during its gametophytic phase, it failed to develop
      sporophytes, indicating that PpMET plays a role in gametogenesis or early
      sporophyte development. Expression array analysis revealed that the deletion of
      PpMET resulted in upregulation of two genes and multiple repetitive sequences. In
      parallel, expression analysis of the previously reported DeltaPpcmt mutant showed
      that lack of PpCMT triggers overexpression of genes. This overexpression combined
      with loss of (m)CHG and its pleiotropic phenotype, implies that PpCMT has an
      essential evolutionary conserved role in the epigenetic control of gene
      expression. Collectively, our results suggest functional conservation of MET1 and
      CMT families during land plant evolution. A model describing the relationship
      between MET1 and CMT in CCG methylation is presented. 

PMID- 25944664
TI  - The prognostic value of plasma soluble CD40 ligand levels following aneurysmal
      subarachnoid hemorrhage.
AB  - BACKGROUND: Increased circulating soluble CD40 ligand (sCD40L) levels have been
      reported to be associated with severity and mortality of severe traumatic brain
      injury. The current study tested the hypothesis that elevated plasma sCD40L
      levels are predictive of clinical outcomes of aneurysmal subarachnoid hemorrhage
      (aSAH). METHODS: Plasma sCD40L concentrations of 120 aSAH patients and 120
      healthy volunteers were measured using enzyme-linked immunosorbent assay. An
      unfavorable outcome was defined as Glasgow Outcome Scale score of 1-3. RESULTS:
      Plasma sCD40L levels were significantly elevated in aSAH patients compared with
      healthy controls; plasma sCD40L levels were highly associated with clinical
      severity reflected by World Federation of Neurological Surgeons (WFNS) score and
      Fisher score; sCD40L emerged as an independent predictor of 6-month mortality and
      unfavorable outcome and 6-month overall survival; although a combined logistic
      regression model did not demonstrate the additive benefit of sCD40L to WFNS score
      and Fisher score, sCD40L possessed similar predictive value to WFNS score and
      Fisher score based on receiver operating characteristic curves. CONCLUSIONS:
      Higher plasma sCD40L levels on presentation are associated with clinical severity
      and have potential to be a good prognostic biomarker of aSAH.

PMID- 25944665
TI  - Culture of human cell lines by a pathogen-inactivated human platelet lysate.
AB  - Alternatives to the use of fetal bovine serum (FBS) have been investigated to
      ensure xeno-free growth condition. In this study we evaluated the efficacy of
      human platelet lysate (PL) as a substitute of FBS for the in vitro culture of
      some human cell lines. PL was obtained by pools of pathogen inactivated human
      donor platelet (PLT) concentrates. Human leukemia cell lines (KG-1, K562, JURKAT,
      HL-60) and epithelial tumor cell lines (HeLa and MCF-7) were cultured with either
      FBS or PL. Changes in cell proliferation, viability, morphology, surface markers
      and cell cycle were evaluated for each cell line. Functional characteristics were
      analysed by drug sensitivity test and cytotoxicity assay. Our results
      demonstrated that PL can support growth and expansion of all cell lines, although
      the cells cultured in presence of PL experienced a less massive proliferation
      compared to those grown with FBS. We found a comparable percentage of viable
      specific marker-expressing cells in both conditions, confirming lineage fidelity
      in all cultures. Functionality assays showed that cells in both FBS- and PL
      supported cultures maintained their normal responsiveness to adriamycin and NK
      cell-mediated lysis. Our findings indicate that PL is a feasible serum substitute
      for supporting growth and propagation of haematopoietic and epithelial cell lines
      with many advantages from a perspective of process standardization, ethicality
      and product safety. 

PMID- 25944666
TI  - Genes as cues: phenotypic integration of genetic and epigenetic information from
      a Darwinian perspective.
AB  - The development of multicellular organisms involves a delicate interplay between
      genetic and environmental influences. It is often useful to think of
      developmental systems as integrating available sources of information about
      current conditions to produce organisms. Genes and inherited physiology provide
      cues, as does the state of the environment during development. The integration
      systems themselves are under genetic control and subject to Darwinian selection,
      so we expect them to evolve to produce organisms that fit well with current
      ecological (including social) conditions. We argue for the scientific value of
      this explicitly informational perspective by providing detailed examples of how
      it can elucidate taxonomically diverse phenomena. We also present a general
      framework for linking genetic and phenotypic variation from an informational
      perspective. This application of Darwinian logic at the organismal level can
      elucidate genetic influences on phenotypic variation in novel and
      counterintuitive ways. 

PMID- 25944667
TI  - Inverse problem-solving helps us to collect the needed data: a reply to Falcy.

PMID- 25944669
TI  - Dimensional accuracy of different techniques used for complete-arch multi-implant
      impressions.
AB  - OBJECTIVE: The aim of this study was to compare the linear horizontal dimensional
      accuracy of the stone casts obtained from four different direct transfer implant
      impression techniques compared with an acrylic master model. METHODS: An acrylic
      resin master model with four implants was fabricated. Four impression techniques
      were used with squared transfer impression copings. These were nonsplinted
      transfer copings, splinted transfer copings, airborne particle-abraded transfer
      copings coated with impression adhesive, and transfer copings with unilateral
      acrylic extension. Dimensional accuracy of the resultant casts was assessed with
      a traveling microscope by recording the linear horizontal distances between the
      most anterior implants and between the most posterior implants. Paired t-test and
      one-way anova followed by Tukey's post hoc test were used for the statistical
      analysis. RESULTS: The results showed a significantly greater anterior and
      posterior horizontal distance in the direct nonsplinted transfer copings
      technique compared with the master model (P < 0.05). When the horizontal
      variations were compared between the four impression techniques, the direct
      nonsplinted transfer copings technique had significantly the greatest anterior
      and posterior horizontal distance in comparison with the other impression
      techniques (P < 0.05). CONCLUSION: Casts obtained from the direct nonsplinted
      transfer impression technique were significantly less accurate than those
      obtained from the other impression techniques used in this study.

PMID- 25944668
TI  - Impact of the serum- and glucocorticoid-inducible kinase 1 on platelet dense
      granule biogenesis and secretion.
AB  - BACKGROUND: Platelet secretion is critical to development of acute thrombotic
      occlusion. Platelet dense granules contain a variety of important hemostatically
      active substances. Nevertheless, biogenesis of platelet granules is poorly
      understood. OBJECTIVES: Serum- and glucocorticoid-inducible kinase 1 (SGK1) has
      been shown to be highly expressed in platelets and megakaryocytes, but its role
      in the regulation of platelet granule biogenesis and its impact on thrombosis has
      not been investigated so far. METHODS AND RESULTS: Electron microscopy analysis
      of the platelet ultrastructure revealed a significant reduction in the number and
      packing of dense granules in platelets lacking SGK1 (sgk1(-/-) ). In sgk1(-/-)
      platelets serotonin content was significantly reduced and activation-dependent
      secretion of ATP, serotonin and CD63 significantly impaired. In vivo adhesion
      after carotis ligation was significantly decreased in platelets lacking SGK1 and
      occlusive thrombus formation after FeCl3 -induced vascular injury was
      significantly diminished in sgk1(-/-) mice. Transcript levels and protein
      abundance of dense granule biogenesis regulating GTPase Rab27b were significantly
      reduced in sgk1(-/-) platelets without affecting Rab27b mRNA stability. In MEG-01
      cells transfection with constitutively active (S422) (D) SGK1 but not with
      inactive (K127) (N) SGK1 significantly enhanced Rab27b mRNA levels. Sgk1(-/-)
      megakaryocytes show significantly reduced expression of Rab27b and serotonin/CD63
      levels compared with sgk1(+/+) megakaryocytes. Proteome analysis identified nine
      further vesicular transport proteins regulated by SGK1, which may have an impact
      on impaired platelet granule biogenesis in sgk1(-/-) platelets independent of
      Rab27b. CONCLUSIONS: The present observations identify SGK1 as a novel powerful
      regulator of platelet dense granule biogenesis, platelet secretion and thrombus
      formation. SGK1 is at least partially effective because it regulates
      transcription of Rab27b in megakaryocytes.

PMID- 25944670
TI  - Dicer cleavage by calpain determines platelet microRNA levels and function in
      diabetes.
AB  - RATIONALE: MicroRNAs (miRNAs) are short noncoding RNA species generated by the
      processing of longer precursors by the ribonucleases Drosha and Dicer. Platelets
      contain large amounts of miRNA that are altered by disease, in particular
      diabetes mellitus. OBJECTIVE: This study determined why platelet miRNA levels are
      attenuated in diabetic individuals and how decreased levels of the platelet
      enriched miRNA, miR-223, affect platelet function. METHODS AND RESULTS: Dicer
      levels were altered in platelets from diabetic mice and patients, a change that
      could be attributed to the cleavage of the enzyme by calpain, resulting in loss
      of function. Diabetes mellitus in human subjects as well as in mice resulted in
      decreased levels of platelet miR-142, miR-143, miR-155, and miR-223. Focusing on
      only 1 of these miRNAs, miR-223 deletion in mice resulted in modestly enhanced
      platelet aggregation, the formation of large thrombi and delayed clot retraction
      compared with wild-type littermates. A similar dysregulation was detected in
      platelets from diabetic patients. Proteomic analysis of platelets from miR-223
      knockout mice revealed increased levels of several proteins, including kindlin-3
      and coagulation factor XIII-A. Whereas, kindlin-3 was indirectly regulated by miR
      223, factor XIII was a direct target and both proteins were also altered in
      diabetic platelets. Treating diabetic mice with a calpain inhibitor prevented
      loss of platelet dicer as well as the diabetes mellitus-induced decrease in
      platelet miRNA levels and the upregulation of miR-223 target proteins.
      CONCLUSIONS: Thus, calpain inhibition may be one means of normalizing platelet
      miRNA processing as well as platelet function in diabetes mellitus.

PMID- 25944671
TI  - High serum sclerostin levels in children with haemophilia A.

PMID- 25944672
TI  - Elucidation of hydroxyl groups-antioxidant relationship in mono- and
      dihydroxyflavones based on O-H bond dissociation enthalpies.
AB  - Radical scavenging potential is the key to anti-oxidation of hydroxyflavones
      which generally found in fruits and vegetables. The objective of this work was to
      investigate the influence of hydroxyl group on the O-H bond dissociation
      enthalpies (BDE) from a series of mono- and dihydroxyflavones. Calculation at the
      B3LYP/6-31G(d,p) level reveals the important roles of an additional one hydroxyl
      group to boost the BDE of hydroxyflavones that were a stabilization of the
      generated radicals through attractive H-bond interactions, an ortho- and para
      dihydroxyl effect, and a presence of the 3-OH in dihydroxyflavones. On the other
      hand, the meta-dihydroxyl effect and range-hydroxyl effect especially associated
      with the either 5-OH or 8-OH promoted greater BDE. Results did not only confirm
      that dihydroxyflavones had lower BDE than monohydroxyflavones but also suggest
      the selective potent hydroxyflavone molecules that are the 6'-hydroxyflavone (for
      monohydroxyflavone) and the 5',6'-, 7,8- and 3',4'-dihydroxyflavone which the
      corresponding radical preferable generated at C6'-O*, C8-O* and C4'-O*,
      respectively. Electron distribution was limited only over the two connected rings
      of hydroxyflavones while the expansion distribution into C-ring could be enhanced
      if the radical was formed especially for the 2',3'- and 5',6'dihydroxyflavone
      radicals. The delocalized bonds were strengthened after radical was generated.
      However the 5-O* in 5,6-dihydroxyflavone and the 3-O* in 3,6'-dihydroxyflavone
      increased the bond order at C4-O11 which might interrupt the conjugated
      delocalized bonds at the keto group. 

PMID- 25944673
TI  - Aromaticity of the completely annelated tetraphenylenes: NICS and GIMIC
      characterization.
AB  - A series of heterocyclic and hydrocarbon [8]circulenes (also named completely
      annelated tetraphenylenes) were studied by the NICS and GIMIC methods in order to
      describe their aromatic properties from the magnetic criterion point of view.
      According to calculations all the hetero[8]circulene molecules demonstrate the
      bifacial aromatic/antiaromatic nature. The inner octatetraene core of the studied
      [8]circulenes is characterized by the presence of paratropic ("antiaromatic")
      ring currents, whereas the outer macrocycle constructed from the five- and six
      membered rings possesses the magnetically-induced diatropic ("aromatic") ring
      current. The hydrocarbon [8]circulenes studied in this work consist of a similar
      planar cyclooctatetraene core but they exhibit a rather different balance of
      magnetically-induced ring currents. 

PMID- 25944675
TI  - Primary care workers are given guidance on managing mental health in humanitarian
      crises.

PMID- 25944674
TI  - Establishing Policy Foundations and Regulatory Systems to Enhance Nursing
      Practice in the United Arab Emirates.
AB  - In 2009, the United Arab Emirates (UAE) established a Nursing and Midwifery
      Council with a mandate to develop standards for the registration and regulation
      of nursing and midwifery and to strengthen the nursing and midwifery workforce.
      Priorities included workforce Emiratization and the development of regulatory
      standards to support advanced and speciality nursing practice and new models of
      care-particularly for the management of noncommunicable diseases. This article
      provides background, context for, and best practice inputs to the effort to
      provide one unified framework of nursing regulation and licensure across the
      whole of the UAE. This article is intended for nurse leaders, policy makers, and
      regulators who are reviewing or developing nursing regulatory processes and
      advancing nursing workforce capacity building activities; and nurse educators and
      nurses wishing to work in the UAE. 

PMID- 25944676
TI  - Histological outcomes after focal high-intensity focused ultrasound and
      cryotherapy.
AB  - INTRODUCTION: Focal therapy has increasingly become an accepted treatment option
      for patients with localised prostate cancer. Most follow-up protocols use a
      mixture of protocol biopsies or "for cause" biopsies triggered by a rising PSA.
      In this paper, we discuss the histological outcomes from these biopsies and their
      use in guiding subsequent management and trial development. METHODS: We conducted
      a literature search and reviewed the post-treatment biopsy results from studies
      on focal HIFU and focal cryotherapy. We subsequently reviewed the results of
      three recently published consensus statements released discussing many of the
      issues concerning focal therapy. RESULTS: Research suggests that 1 in 5 of all
      post-treatment biopsies after focal therapy are positive. However, the majority
      of these seemed to be from the untreated portion of the gland or met criteria for
      clinically insignificant disease. The histological outcomes from focal therapy
      are promising and confirm its effectiveness in the short to medium term.
      Furthermore re-treatment is possible whilst maintaining a low-side-effect
      profile. CONCLUSION: Debate is ongoing about the clinical significance of various
      levels of residual disease after focal therapy and the exact threshold at which
      to call failure within a patient who has had focal therapy.

PMID- 25944677
TI  - Functional magnetic resonance imaging and molecular pathology at the crossroad of
      the management of early prostate cancer.
AB  - INTRODUCTION: According to recent reports from randomized studies comparing
      radical treatment or watchful waiting, the outcome of localized prostate cancer
      remains uncertain at individual level. It is especially true for the low-risk
      group (according D'Amico or CAPRA classifications), regarding the individual
      exposition to overtreatment by radical therapies or the opposite risk of under
      treatment with active surveillance. MATERIAL AND METHODS: In this review, we
      describe the available molecular predictor tests and functional MRI, as well as
      their potential role in the selection of the appropriate treatment for prostate
      cancer patients. CONCLUSION: The recent development of functional MRI imaging and
      clinical practice approval of molecular predictor tests for the assessment of the
      aggressive prostate cancer have brought new perspectives for the management of
      localized prostate cancer by active surveillance, focal ablative therapy or
      radical therapies.

PMID- 25944678
TI  - Perioperative outcome and female sexual function after laparoscopic transvaginal
      NOTES-assisted nephrectomy.
AB  - PURPOSE: There is a concern about the impact that this surgery could have on a
      patient's sexuality, although this has not been well documented. The objective of
      our study is to describe the surgical results and assess sexual function and
      patient satisfaction after transvaginal NOTES-assisted laparoscopic radical and
      living donor nephrectomy. METHODS: Between March 2008 and October 2014, 100 women
      underwent transvaginal NOTES-assisted nephrectomy (78 living donor and 22 radical
      nephrectomy) in our centre. The procedure was performed using two different
      techniques depending on the indication as described previously, but using the
      same vaginal approach. Variables evaluated were operative time, blood loss, intra
      operative complications, hospital stay, satisfaction, first-month creatinine and
      warm ischaemia time in donors. Sexual function was assessed with the Female
      Sexual Function Index questionnaire before and after surgery. All variables were
      accrued in a prospective database. RESULTS: The procedure was completed in all
      cases. Mean age and body mass index was higher in the radical nephrectomy group.
      Mean operative time and hospital stay were similar for both techniques. All
      sexually active women reported unaltered sexual function after surgery and
      satisfaction with the results. The pre- and post-FSFI scores for living donor (n
      = 54) and radical nephrectomy (n = 4) were 27.47 +/- 1.02/27.27 +/- 1.10 (p >
      0.05) and 31.17 +/- 0.81/31.87 +/- 0.97 (p > 0.05). CONCLUSIONS: Transvaginal
      NOTES-assisted or hybrid NOTES nephrectomy offers a safe technique with excellent
      cosmetic results and no sexual effect. Despite promising results, randomized
      controlled studies with longer follow-up are warranted to further elucidate the
      potential of this novel technique.

PMID- 25944679
TI  - A hybrid actuated microrobot using an electromagnetic field and flagellated
      bacteria for tumor-targeting therapy.
AB  - In this paper, we propose a new concept for a hybrid actuated microrobot for
      tumor-targeting therapy. For drug delivery in tumor therapy, various
      electromagnetic actuated microrobot systems have been studied. In addition,
      bacteria-based microrobot (so-called bacteriobot), which use tumor targeting and
      the therapeutic function of the bacteria, has also been proposed for solid tumor
      therapy. Compared with bacteriobot, electromagnetic actuated microrobot has
      larger driving force and locomotive controllability due to their position
      recognition and magnetic field control. However, because electromagnetic actuated
      microrobot does not have self-tumor targeting, they need to be controlled by an
      external magnetic field. In contrast, the bacteriobot uses tumor targeting and
      the bacteria's own motility, and can exhibit self-targeting performance at solid
      tumors. However, because the propulsion forces of the bacteria are too small, it
      is very difficult for bacteriobot to track a tumor in a vessel with a large
      bloodstream. Therefore, we propose a hybrid actuated microrobot combined with
      electromagnetic actuation in large blood vessels with a macro range and bacterial
      actuation in small vessels with a micro range. In addition, the proposed
      microrobot consists of biodegradable and biocompatible microbeads in which the
      drugs and magnetic particles can be encapsulated; the bacteria can be attached to
      the surface of the microbeads and propel the microrobot. We carried out macro
      manipulation of the hybrid actuated microrobot along a desired path through
      electromagnetic field control and the micro-manipulation of the hybrid actuated
      microrobot toward a chemical attractant through the chemotaxis of the bacteria.
      For the validation of the hybrid actuation of the microrobot, we fabricated a
      hydrogel microfluidic channel that can generate a chemical gradient. Finally, we
      evaluated the motility performance of the hybrid actuated microrobot in the
      hydrogel microfluidic channel. We expect that the hybrid actuated microrobot will
      be utilized for tumor targeting and therapy in future.

PMID- 25944680
TI  - Evaluating patient experience in a cystic fibrosis centre using a disease
      specific patient satisfaction questionnaire.
AB  - Medical care for persons with chronic diseases like cystic fibrosis (CF) is
      provided by multi-professional teams. We assessed the patients' perspective of
      care by reporting the results of two consecutive patient satisfaction surveys
      performed within a 2-year interval at our CF centre. The newly developed, disease
      specific questionnaire for parents and adults had 104 items with up to 6 response
      categories each. For data analysis, responses were dichotomized into a problem
      score with 0 % as the ideal result. Adolescents were surveyed using a different
      questionnaire. Seventy-six and 89 respondents, respectively, took part in the
      2009 and 2011 surveys (response rates: 72 to 84 %). In 2009, the ideal problem
      score of 0 % was reported for 18 and 20 % of all items in adults and parents,
      respectively. Thirteen items had a problem score >30 %. After the whole team had
      implemented quality improvement measures, the 2011 survey showed a >10 % decrease
      in problem scores for 11 and 21 % of items in the adults and parents groups,
      respectively. Adolescents also reported better experiences in 2011 than in 2009.
      CONCLUSION: Exploring the patients' perspectives aids to identify strengths and
      weaknesses and helps to provide patient-centred care, which is important for
      persons with chronic illness.

PMID- 25944682
TI  - Oral psoriasis-a diagnostic dilemma: a report of two cases and a review of the
      literature.
AB  - Whether psoriasis can manifest itself in the oral mucosa has been a matter of
      debate for many years. If an oral version of psoriasis exists, most researchers
      regard this manifestation as rare. The present report describes two patients who
      presented with lesions possibly related to cutaneous psoriasis. One patient had
      patchy erythematous lesions on the gingiva, and one had serpiginous lesions in
      the hard palate. We discuss these cases in relation to the existing literature,
      with special emphasis on the clinical and histopathologic criteria for the
      diagnosis of oral psoriasis. 

PMID- 25944683
TI  - Gate Modulation of Graphene-ZnO Nanowire Schottky Diode.
AB  - Graphene-semiconductor interface is important for the applications in electronic
      and optoelectronic devices. Here we report the modulation of the electric
      transport properties of graphene/ZnO nanowire Schottky diode by gate voltage
      (Vg). The ideality factor of the graphene/ZnO nanowire Schottky diode is ~1.7,
      and the Schottky barrier height is ~0.28 eV without external Vg. The Schottky
      barrier height is sensitive to Vg due to the variation of Fermi level of
      graphene. The barrier height increases quickly with sweeping Vg towards the
      negative value, while decreases slowly towards the positive Vg. Our results are
      helpful to understand the fundamental mechanism of the electric transport in
      graphene-semiconductor Schottky diode. 

PMID- 25944685
TI  - Man versus Machine: Comparison of Automated and Manual Methodologies for
      Measuring the QTc Interval: A Prospective Study.
AB  - BACKGROUND: Electrocardiographic (ECG) safety evaluation is a required element of
      drug development. Performance characteristics of ECG measurement methodologies
      have rarely been studied prospectively. METHODS: We conducted a randomized,
      placebo-controlled, crossover study in 24 subjects to evaluate effects of
      moxifloxacin on the Fridericia rate-corrected QT (QTcF) interval. Five ECG
      replicates were obtained at 30 time points. Change from baseline QTcF (DeltaQTcF)
      was fit by mixed-model analysis of variance to evaluate residual standard
      deviation. Precision was defined as intrasubject QTcF variance. Two core lab
      approaches were compared: QTinno, fully automated, 5 replicates and HeartSignals,
      computer-assisted manual, 3 replicates. Core lab values were then compared to an
      automated commercial algorithm (VERITAS). RESULTS: Twenty-three subjects provided
      3450 ECGs potentially available for analysis. QTinno QTcF values were based upon
      3419 ECGs, HeartSignals data on 2028 ECGs. Variance was similar between the
      QTinno and HeartSignals approaches (41.5 and 44 ms(2)). After excluding VERITAS
      QTcF measurements that deviated by >40 ms on visual review, variance in a set of
      1907 common ECGs was lowest for HeartSignal, followed by QTinno and VERITAS
      (43.8, 52.6, 89.4 ms(2)) P = 0.02 HeartSignals versus QTinno, P < 0.0001 for both
      HeartSignals and QTinno versus VERITAS. CONCLUSIONS: A fully automated core lab
      approach using 5 replicates and a computer-assisted manual approach using 3
      replicates were equally precise. When an identical number of ECGs were compared,
      the computer-assisted manual method was most precise, while the commercial
      algorithm was relatively imprecise. Although suitable for clinical assessment the
      standard commercial algorithm cannot be recommended for regulated safety
      research.

PMID- 25944684
TI  - Vasoactive intestinal peptide suppresses macrophage-mediated inflammation by
      downregulating interleukin-17A expression via PKA- and PKC-dependent pathways.
AB  - Interleukin (IL)-17A is a pro-inflammatory cytokine that markedly enhances
      inflammatory responses in the lungs by recruiting neutrophils and interacting
      with other pro-inflammatory mediators. Reducing the expression of IL-17A could
      attenuate inflammation in the lungs. However, whether VIP exerts its anti
      inflammatory effects by regulating the expression of IL-17A has remained unclear.
      Here, we show that there is a remarkable increase of IL-17A in bronchoalveolar
      lavage fluid (BALF) and lung tissue of mice with acute lung injury (ALI).
      Moreover, lipopolysaccharides (LPS) stimulated elevated expression of IL-17A,
      which was evident by the enhanced levels of mRNA and protein observed.
      Furthermore, we also found that VIP inhibited LPS-mediated IL-17A expression in a
      time- and dose-dependent manner in an in vitro model of ALI and that this process
      might be mediated via the phosphokinase A (PKA) and phosphokinase C (PKC)
      pathways. Taken together, our results demonstrated that VIP might be an effective
      protector during ALI by suppressing IL-17A expression.

PMID- 25944686
TI  - Absolute quantification of the pretreatment PML-RARA transcript defines the
      relapse risk in acute promyelocytic leukemia.
AB  - In this study we performed absolute quantification of the PML-RARA transcript by
      droplet digital polymerase chain reaction (ddPCR) in 76 newly diagnosed acute
      promyelocytic leukemia (APL) cases to verify the prognostic impact of the PML
      RARA initial molecular burden. ddPCR analysis revealed that the amount of PML
      RARA transcript at diagnosis in the group of patients who relapsed was higher
      than in that with continuous complete remission (CCR) (272 vs 89.2 PML-RARA
      copies/ng, p = 0.0004, respectively). Receiver operating characteristic analysis
      detected the optimal PML-RARA concentration threshold as 209.6 PML-RARA/ng (AUC
      0.78; p < 0.0001) for discriminating between outcomes (CCR versus relapse). Among
      the 67 APL cases who achieved complete remission after the induction treatment,
      those with >209.6 PML-RARA/ng had a worse relapse-free survival (p = 0.0006). At
      5-year follow-up, patients with >209.6 PML-RARA/ng had a cumulative incidence of
      relapse of 50.3% whereas 7.5% of the patients with suffered a relapse (p <
      0.0001). Multivariate analysis identified the amount of PML-RARA before induction
      treatment as the sole independent prognostic factor for APL relapse.Our results
      show that the pretreatment PML-RARA molecular burden could therefore be used to
      improve risk stratification in order to develop more individualized treatment
      regimens for high-risk APL cases. 

PMID- 25944687
TI  - Wedelolactone disrupts the interaction of EZH2-EED complex and inhibits PRC2
      dependent cancer.
AB  - Polycomb repressive complex 2 (PRC2), which is responsible for the trimethylation
      of H3K27 (H3K27me3), plays a part in tumorigenesis, development and/or
      maintenance of adult tissue specificity. The pivotal role of PRC2 in cancer makes
      it a therapeutic target for epigenetic cancer therapy. However, natural compounds
      targeting the enhancer of zeste homolog 2 (EZH2) - embryonic ectoderm development
      (EED) interaction to disable PRC2 complex are scarcely reported. Here, we
      reported the screening and identification of natural compounds which could
      disrupt the EZH2-EED interaction. One of these compounds, wedelolactone, binds to
      EED with a high affinity (KD = 2.82 MUM), blocks the EZH2-EED interaction in
      vitro, induces the degradation of PRC2 core components and modulates the
      expression of detected PRC2 downstream targets and cancer-related genes.
      Furthermore, some PRC2-dependent cancer cells undergone growth arrest upon
      treatment with wedelolactone. Thus, wedelolactone and its derivatives which
      target the EZH2-EED interaction could be candidates for the treatment of PRC2
      dependent cancer. 

PMID- 25944688
TI  - Printed peptide arrays identify prognostic TNC serumantibodies in glioblastoma
      patients.
AB  - Liquid biopsies come of age offering unexploited potential to monitor and react
      to tumor evolution. We developed a cost-effective assay to non-invasively
      determine the immune status of glioblastoma (GBM) patients. Employing newly
      developed printed peptide microarrays we assessed the B-cell response against
      tumor-associated antigens (TAAs) in 214 patients. Firstly, sera of long-term (36+
      months, LTS, n=10) and short-term (6-10 months, STS, n=14) surviving patients
      were screened for prognostic antibodies against 1745 13-mer peptides covering
      known TAAs (TNC, EGFR, GLEA2, PHF3, FABP5, MAGEA3). Next, survival associations
      were investigated in two retrospective independent multicenter validation sets
      (n=61, n=129, all IDH1-wildtype). Reliability of measurements was tested using a
      second array technology (spotted arrays). LTS/STS screening analyses identified
      106 differential antibody responses. Evaluating the Top30 peptides in validation
      set 1 revealed three prognostic peptides. Prediction of TNC peptide VCEDGFTGPDCAE
      was confirmed in a second set (p=0.043, HR=0.66 [0.44-0.99]) and was unrelated to
      TNC protein expression. Median signals of printed arrays correlated with pre
      synthesized spotted microarrays (p<0.0002, R=0.33). Multiple survival analysis
      revealed independence of age, gender, KPI and MGMT status. We present a novel
      peptide microarray immune assay that identified increased anti-TNC VCEDGFTGPDCAE
      serum antibody titer as a promising non-invasive biomarker for prolonged
      survival. 

PMID- 25944689
TI  - Addition of rapamycin and hydroxychloroquine to metronomic chemotherapy as a
      second line treatment results in high salvage rates for refractory metastatic
      solid tumors: a pilot safety and effectiveness analysis in a small patient
      cohort.
AB  - BACKGROUND: Autophagy is an important oncotarget that can be modulated during
      anti-cancer therapy. Enhancing autophagy using chemotherapy and rapamycin (Rapa)
      treatment and then inhibiting it using hydroxychloroquine (HCQ) could
      synergistically improve therapy outcome in cancer patients. It is still unclear
      whether addition of Rapa and HCQ to chemotherapy could be used for reversing drug
      resistance. PATIENTS AND METHODS: Twenty-five stage IV cancer patients were
      identified. They had no clinical response to first-line metronomic chemotherapy;
      the patients were salvaged by adding an autophagy inducer (Rapa, 2 mg/day) and an
      autophagosome inhibitor (HCQ, 400 mg/day) to their current metronomic
      chemotherapy for at least 3 months. Patients included 4 prostate, 4 bladder, 4
      lung, 4 breast, 2 colon, and 3 head and neck cancer patients as well as 4 sarcoma
      patients. RESULTS: Chemotherapy was administered for a total of 137 months. The
      median duration of chemotherapy cycles per patient was 4 months (95% confidence
      interval, 3-7 months). The overall response rate to this treatment was of 40%,
      with an 84% disease control rate. The most frequent and clinically significant
      toxicities were myelotoxicities. Grade >=3 leucopenia occurred in 6 patients
      (24%), grade >=3 thrombocytopenia in 8 (32%), and anemia in 3 (12%). None of them
      developed febrile neutropenia. Non-hematologic toxicities were fatigue (total
      32%, with 1 patient developing grade 3 fatigue), diarrhea (total 20%, 1 patient
      developed grade 3 fatigue), reversible grade 3 cardiotoxicity (1 patient), and
      grade V liver toxicity from hepatitis B reactivation (1 patient). CONCLUSION: Our
      results of Rapa, HCQ and chemotherapy triplet combination suggest autophagy is a
      promising oncotarget and warrants further investigation in phase II studies.

PMID- 25944690
TI  - FGF23 is elevated in multiple myeloma and increases heparanase expression by
      tumor cells.
AB  - Multiply myeloma (MM) grows in and destroys bone, where osteocytes secrete FGF23,
      a hormone which affects phosphate homeostasis and aging. We report that multiple
      myeloma (MM) cells express receptors for and respond to FGF23. FGF23 increased
      mRNA for EGR1 and its target heparanase, a pro-osteolytic factor in MM. FGF23
      signals through a complex of klotho and a classical FGF receptor (FGFR); both
      were expressed by MM cell lines and patient samples. Bone marrow plasma cells
      from 42 MM patients stained positively for klotho, while plasma cells from 8
      patients with monoclonal gammopathy of undetermined significance (MGUS) and 6
      controls were negative. Intact, active FGF23 was increased 2.9X in sera of MM
      patients compared to controls. FGF23 was not expressed by human MM cells, but co
      culture with mouse bone increased its mRNA. The FGFR inhibitor NVP-BGJ398 blocked
      the heparanase response to FGF23. NVP-BGJ398 did not inhibit 8226 growth in vitro
      but significantly suppressed growth in bone and induction of the osteoclast
      regulator RANK ligand, while decreasing heparanase mRNA. The bone
      microenvironment provides resistance to some anti-tumor drugs but increased the
      activity of NVP-BGJ398 against 8226 cells. The FGF23/klotho/heparanase signaling
      axis may offer targets for treatment of MM in bone. 

PMID- 25944691
TI  - Activation of insulin-like growth factor 1 receptor in patients with non-small
      cell lung cancer.
AB  - According to previous reports demonstrating the implication of insulin-like
      growth factor receptor (IGF-1R) signaling in non-small cell lung cancer (NSCLC),
      in this study, the potential prognostic values of IGF-1R expression/activation
      were analyzed. The expression and activation of IGF-1R were evaluated in two
      tissue microarray (TMA) sets from NSCLC patients (N = 352 for TMA I, and N = 353
      for TMA II). Alterations in IGF-1R protein or mRNA expression in NSCLC patients
      were evaluated using publicly available data from The Cancer Genome Atlas (TCGA).
      We found that membranous and cytoplasmic IGF-1R expressions were significantly
      associated with squamous cell carcinoma (SCC) in both of the TMAs. Analysis of
      the TCGA data revealed increased mRNA levels in NSCLC patients, which was
      significantly associated with reductions in overall survival (OS) (median
      survival 26.51 vs. 47.77 months, P = 0.017) and disease-free survival (median
      survival 17.44 vs. 37.65 months, P = 0.045) only in NSCLC patients with
      adenocarcinoma (ADC). These data suggest that IGF-1R is activated in patients
      with NSCLC, particularly those with SCC. IGF-1R mRNA expression is a potential
      prognostic factor in patients with NSCLC, especially those with ADC. Further
      studies are warranted to investigate the prognostic value of IGF-1R in NSCLC
      patients.

PMID- 25944692
TI  - Proteogenomic analysis reveals exosomes are more oncogenic than ectosomes.
AB  - Extracellular vesicles (EVs) include the exosomes (30-100 nm) that are produced
      through the endocytic pathway via the multivesicular bodies and the ectosomes
      (100-1000 nm) that are released through the budding of the plasma membrane.
      Despite the differences in the mode of biogenesis and size, reliable markers that
      can distinguish between exosomes and ectosomes are non-existent. Moreover, the
      precise functional differences between exosomes and ectosomes remains poorly
      characterised. Here, using label-free quantitative proteomics, we highlight
      proteins that could be exploited as markers to discriminate between exosomes and
      ectosomes. For the first time, a global proteogenomics analysis unveiled the
      secretion of mutant proteins that are implicated in cancer progression through
      tumor-derived EVs. Follow up integrated bioinformatics analysis highlighted the
      enrichment of oncogenic cargo in exosomes and ectosomes. Interestingly, exosomes
      induced significant cell proliferation and migration in recipient cells compared
      to ectosomes confirming the oncogenic nature of exosomes. These findings
      ascertain that cancer cells facilitate oncogenesis by the secretion of mutant and
      oncoproteins into the tumor microenvironment via exosomes and ectosomes. The
      integrative proteogenomics approach utilized in this study has the potential to
      identify disease biomarker candidates which can be later assayed in liquid
      biopsies obtained from cancer patients. 

PMID- 25944693
TI  - RAS testing in metastatic colorectal cancer: excellent reproducibility amongst 17
      Dutch pathology centers.
AB  - In 2013 the European Medicine Agency (EMA) restricted the indication for anti
      EGFR targeted therapy to metastatic colorectal cancer (mCRC) with a wild-type RAS
      gene, increasing the need for reliable RAS mutation testing. We evaluated the
      completeness and reproducibility of RAS-testing in the Netherlands. From 17
      laboratories, tumor DNA of the first 10 CRC cases tested in 2014 in routine
      clinical practice was re-tested by a reference laboratory using a custom next
      generation sequencing panel. In total, 171 CRC cases were re-evaluated for
      hotspot mutations in KRAS, NRAS and BRAF. Most laboratories had introduced
      complete RAS-testing (65%) and BRAF-testing (71%) by January 2014. The most
      employed method for all hotspot regions was Sanger sequencing (range 35.7 -
      49.2%). The reference laboratory detected all mutations that had been found in
      the participating laboratories (n = 92), plus 10 additional mutations. This
      concerned three RAS and seven BRAF mutations that were missed due to incomplete
      testing of the participating laboratory. Overall, the concordance of tests
      performed by both the reference and participating laboratory was 100% (163/163;
      kappa-static 1.0) for RAS and 100% (144/144; kappa-static 1.0) for BRAF. Our
      study shows that RAS and BRAF mutations can be reproducibly assessed using a
      variety of testing methods.

PMID- 25944694
TI  - Prevalence and predictive factors of osteoporosis in systemic sclerosis patients:
      a case-control study.
AB  - PURPOSE: Investigate the prevalence of osteoporosis in patients with systemic
      sclerosis (SSc) and describe alterations of bone tissue with High-Resolution
      peripheral Quantitative Computed Tomography (HR-pQCT). METHODS: Thirty-three
      patients and 33 controls matched on age, body mass index (BMI) and menopause were
      included. Bone mineral density (BMD) was measured at the lumbar spine (LS),
      femoral neck (FN) and total hip (TH) by dual energy X-ray absorptiometry.
      Volumetric BMD (vBMD) and bone microarchitecture were measured by HR-pQCT at
      tibia and radius. RESULTS: In patients, BMI was significantly lower, the
      prevalence of osteoporosis was significantly higher and HR-pQCT analysis showed a
      significant alteration of the trabecular compartment with a decrease in
      trabecular vBMD on both sites than in controls. In multivariate analysis, a low
      lean body mass, presence of anticentromere antibodies and older age were
      identified as independent factors for decreased BMD at LS (r2=0.43), FN (r2=0.61)
      and TH (r2=0.73). History or current digital ulcers were also identified as an
      independent factor for microarchitecture alteration. CONCLUSIONS: In patients an
      increased prevalence of osteoporosis was found and HR-pQCT showed impaired
      trabecular bone compartment. Also, low lean body mass, high age, digital ulcers
      and ACAs were identified as independent risk factors for bone damage.

PMID- 25944695
TI  - Irreversible dual inhibitory mode: the novel Btk inhibitor PLS-123 demonstrates
      promising anti-tumor activity in human B-cell lymphoma.
AB  - The B-cell receptor (BCR) signaling pathway has gained significant attention as a
      therapeutic target in B-cell malignancies. Recently, several drugs that target
      the BCR signaling pathway, especially the Btk inhibitor ibrutinib, have
      demonstrated notable therapeutic effects in relapsed/refractory patients, which
      indicates that pharmacological inhibition of BCR pathway holds promise in B-cell
      lymphoma treatment. Here we present a novel covalent irreversible Btk inhibitor
      PLS-123 with more potent anti-proliferative activity compared with ibrutinib in
      multiple cellular and in vivo models through effective apoptosis induction and
      dual-action inhibitory mode of Btk activation. The phosphorylation of BCR
      downstream activating AKT/mTOR and MAPK signal pathways was also more
      significantly reduced after treatment with PLS-123 than ibrutinib. Gene
      expression profile analysis further suggested that the different selectivity
      profile of PLS-123 led to significant downregulation of oncogenic gene PTPN11
      expression, which might also offer new opportunities beyond what ibrutinib has
      achieved. In addition, PLS-123 dose-dependently attenuated BCR- and chemokine
      mediated lymphoma cell adhesion and migration. Taken together, Btk inhibitor PLS
      123 suggested a new direction to pharmacologically modulate Btk function and
      develop novel therapeutic drug for B-cell lymphoma treatment. 

PMID- 25944696
TI  - Involvement of multiple myeloma cell-derived exosomes in osteoclast
      differentiation.
AB  - Bone disease is the most frequent complication in multiple myeloma (MM) resulting
      in osteolytic lesions, bone pain, hypercalcemia and renal failure. In MM bone
      disease the perfect balance between bone-resorbing osteoclasts (OCs) and bone
      forming osteoblasts (OBs) activity is lost in favour of OCs, thus resulting in
      skeletal disorders. Since exosomes have been described for their functional role
      in cancer progression, we here investigate whether MM cell-derived exosomes may
      be involved in OCs differentiation. We show that MM cells produce exosomes which
      are actively internalized by Raw264.7 cell line, a cellular model of osteoclast
      formation. MM cell-derived exosomes positively modulate pre-osteoclast migration,
      through the increasing of CXCR4 expression and trigger a survival pathway. MM
      cell-derived exosomes play a significant pro-differentiative role in murine
      Raw264.7 cells and human primary osteoclasts, inducing the expression of
      osteoclast markers such as Cathepsin K (CTSK), Matrix Metalloproteinases 9 (MMP9)
      and Tartrate-resistant Acid Phosphatase (TRAP). Pre-osteoclast treated with MM
      cell-derived exosomes differentiate in multinuclear OCs able to excavate
      authentic resorption lacunae. Similar results were obtained with exosomes derived
      from MM patient's sera. Our data indicate that MM-exosomes modulate OCs function
      and differentiation. Further studies are needed to identify the OCs activating
      factors transported by MM cell-derived exosomes. 

PMID- 25944697
TI  - Tag SNPs in long non-coding RNA H19 contribute to susceptibility to gastric
      cancer in the Chinese Han population.
AB  - Long non-coding RNA (lncRNA) H19 is involved in tumor development, progression,
      and metastasis. This case-control study assessed the association between H19
      genetic variants and susceptibility to gastric cancer (GC) in a Chinese Han
      population. We genotyped four lncRNA H19 single nucleotide polymorphisms (SNPs)
      (rs217727 C > T, rs2839698 C > T, rs3741216 A > T, rs3741219 T > C) in 500 GC
      patients and 500 healthy controls. Carriers of variant rs217727T and rs2839698T
      alleles showed increased GC risk (P = 0.008 and 0.011, respectively). Compared
      with the common genotype, CT + TT rs217727 and CT + TT rs2839698 genotypes were
      associated with significantly increased GC risk (P = 0.040, adjusted odds ratio
      [OR] = 1.32, 95% confidence interval [CI] = 1.01-1.71; P = 0.033, adjusted OR =
      1.31, 95% CI = 1.02-1.69, respectively). Further stratified analyses revealed
      that the association between GC risk and variant genotypes of rs217727 was more
      profound in younger individuals (<=59 years) and non-smokers, while the
      association between risk and the rare rs2839698 genotype persisted in men and
      rural subjects. rs2839698 CT and TT genotypes were also associated with higher
      serum H19 mRNA levels compared with the CC genotype. These findings suggest that
      lncRNA H19 SNPs may contribute to susceptibility to GC. 

PMID- 25944698
TI  - Differential gene expression in human abdominal aortic aneurysm and aortic
      occlusive disease.
AB  - Abdominal aortic aneurysm (AAA) and aortic occlusive disease (AOD) represent
      common causes of morbidity and mortality in elderly populations which were
      previously believed to have common aetiologies. The aim of this study was to
      assess the gene expression in human AAA and AOD. We performed microarrays using
      aortic specimen obtained from 20 patients with small AAAs (<= 55mm), 29 patients
      with large AAAs (> 55mm), 9 AOD patients, and 10 control aortic specimens
      obtained from organ donors. Some differentially expressed genes were validated by
      quantitative-PCR (qRT-PCR)/immunohistochemistry. We identified 840 and 1,014
      differentially expressed genes in small and large AAAs, respectively. Immune
      related pathways including cytokine-cytokine receptor interaction and T-cell
      receptor signalling were upregulated in both small and large AAAs. Examples of
      validated genes included CTLA4 (2.01-fold upregulated in small AAA, P = 0.002),
      NKTR (2.37-and 2.66-fold upregulated in small and large AAA with P = 0.041 and P
      = 0.015, respectively), and CD8A (2.57-fold upregulated in large AAA, P = 0.004).
      1,765 differentially expressed genes were identified in AOD. Pathways upregulated
      in AOD included metabolic and oxidative phosphorylation categories. The UCP2 gene
      was downregulated in AOD (3.73-fold downregulated, validated P = 0.017). In
      conclusion, the AAA and AOD transcriptomes were very different suggesting that
      AAA and AOD have distinct pathogenic mechanisms. 

PMID- 25944699
TI  - Transplacental passage of antimicrobial paraben preservatives.
AB  - Parabens are widely used preservatives suspected of being endocrine disruptors,
      with implications for human growth and development. The most common paraben found
      in consumer products is methylparaben. To date, no study has examined whether
      these substances cross the human placenta. A total of 100 study subjects (50
      mother-child pairs) were enrolled at two medical institutions, serving primarily
      African-American and Caucasian women, respectively. A maternal blood sample was
      drawn on admission and a paired cord blood sample was obtained at delivery. Of
      the 50 mothers, 47 (94%) showed methylparaben in their blood (mean level 20.41
      ng/l), and 47 in cords bloods (mean level 36.54 ng/l). There were 45 mother-child
      pairs where methylparaben was found in both samples. Of these, the fetal level
      was higher than the maternal level in 23 (51%). For butylparaben, only 4 mothers
      (8%) showed detectable levels (mean 40.54 ng/l), whereas 8 cord blood samples
      (16%) were positive (mean 32.5 ng/l). African-American mothers and infants showed
      higher prevalence of detectable levels (P=0.017). Methylparaben and butylparaben
      demonstrate transplacental passage. Additional studies are needed to examine
      potential differences in exposure by geography and demographics, what products
      are used by pregnant women that contain these preservatives, as well as any
      potential long-term effects in the growth and development of exposed children. 

PMID- 25944700
TI  - Evaluating narrow windows of maternal exposure to ozone and preterm birth in a
      large urban area in Southeast Texas.
AB  - The association between O3 exposure and preterm birth (PTB) remains unclear. We
      evaluated associations for three categories of PTB and O3 in Harris County,
      Texas, during narrow periods of gestation. We computed two sets of exposure
      metrics during every 4 weeks of pregnancy for 152,214 mothers who delivered
      singleton, live-born infants in 2005-2007, accounting first for temporal
      variability and then for temporal and spatial sources of variability in ambient
      O3 levels. Associations were assessed using multiple logistic regression. We also
      examined the potential for a fixed cohort bias. In the bias-corrected cohort
      where associations were somewhat stronger, elevated odds ratios (ORs) per 10
      parts per billion increase in O3 exposure (county-level metric) were detected for
      the fifth (OR=1.08, 95% confidence interval (CI): 1.04-1.12), sixth (OR=1.05, 95%
      CI=1.01-1.09), and seventh (OR=1.07, 95% CI=1.03-1.10) 4-week periods of
      pregnancy for late PTB (33-36 completed weeks gestation), the fifth (OR=1.13, 95%
      CI=1.02-1.25) and seventh (OR=1.15, 95% CI=1.04-1.27) 4-week periods of pregnancy
      for moderate PTB (29-32 completed weeks gestation), and the fifth (OR=1.21, 95%
      CI=1.08-1.36) 4-week period of pregnancy for severe PTB (20-28 completed weeks
      gestation). Conversely, decreased odds were found in the first 4-week period of
      pregnancy for severe PTB (OR=0.83, 95% CI=0.74-0.94). Associations were slightly
      attenuated using the spatially interpolated (kriged) metrics, and for women who
      did not work outside of the home. Our analyses confirm reports in other parts of
      the United States and elsewhere with findings that suggest that maternal exposure
      to ambient levels of O3 is associated with PTB. 

PMID- 25944701
TI  - Assessment of phthalates/phthalate alternatives in children's toys and childcare
      articles: Review of the report including conclusions and recommendation of the
      Chronic Hazard Advisory Panel of the Consumer Product Safety Commission.
AB  - The Consumer Product Safety Commission (CPSC) convened a Chronic Hazard Advisory
      Panel (CHAP) on Phthalates found in children's toys, and childcare products, and
      in products used by women of childbearing age. The CHAP conducted a risk
      assessment on phthalates and phthalate substitutes, and made recommendations to
      either ban, impose an interim ban, or allow the continued use of phthalates and
      phthalate substitutes in the above products. After a review of the literature,
      the evaluation included toxic end points of primary concern, biomonitoring
      results, extant exposure reconstruction, and epidemiological results. The health
      end points chosen were associated with the rat phthalate syndrome, which is
      characterized by malformations of the epididymis, vas deferens, seminal vesicles,
      prostate, external genitalia (hypospadias), and by cryptorchidism (undescended
      testes), retention of nipples/areolae, and demasculinization (~incomplete
      masculinization) of the perineum, resulting in reduced anogenital distance. Risk
      assessment demonstrated that some phthalates should be permanently banned,
      removed from the banned list, or remain interim banned. Biomonitoring and
      toxicology data provided the strongest basis for a mixture risk assessment. In
      contrast, external exposure data were the weakest and need to be upgraded for
      epidemiological studies and risk assessments. Such studies would focus on routes
      and sources. The review presents recommendations and uncertainties. 

PMID- 25944703
TI  - Cobalt-catalyzed transformation of molecular dinitrogen into silylamine under
      ambient reaction conditions.
AB  - The first successful example of cobalt-catalyzed reduction of N2 with Me3 SiCl
      and Na as a reductant, under ambient reaction conditions, gives N(SiMe3 )3 ,
      which can be readily converted into NH3 . In this reaction system, 2,2'
      bipyridine (bpy) is found to work as an effective additive to improve
      substantially the catalytic activity. Co?N2 complexes bearing three Me3 Si groups
      as ancillary ligands are considered to work as key reactive species based on DFT
      calculations. The DFT results also allow the proposal of a detailed reaction
      pathway for the transformation of N2 into N(SiMe3 )3 . 

PMID- 25944702
TI  - An increased prevalence of thyroid disease in children with 22q11.2 deletion
      syndrome.
AB  - We reviewed the health records of pediatric patients with 22q11.2 deletion
      syndrome (22q11.2 DS) seen over a 5-year period in our 22q11.2 DS
      multidisciplinary clinic. We determined the prevalence of thyroid dysfunction in
      this population, in comparison to general population data. Statistical tests were
      applied to investigate trends in gender differences, thyroid disease subtype and
      co-morbid conditions in the patients identified with thyroid disease. Of 169
      subjects (92 male, 77 female) 9.5% had overt thyroid disease; of these, 1.8% had
      hyperthyroidism and 7.7% had hypothyroidism; 42% of patients with subclinical or
      prodromal thyroid disease progressed to overt disease. Our data indicate that
      thyroid disease prevalence in the 22q11DS pediatric population is significantly
      higher than that in the general pediatric population Furthermore, over 1/3 of
      patients in our study population who presented with subclinical thyroid disease
      progressed to overt disease, requiring medical therapy. Thyroid disease screening
      should be incorporated into routine medical management of children with 22q11.2
      DS. Guidelines for screening individuals with 22q11.2 DS are presented.

PMID- 25944704
TI  - Does pay-for-performance benefit patients with multiple chronic conditions?
      Evidence from a universal coverage health care system.
AB  - INTRODUCTION: Numerous studies have examined the impact of pay-for-performance
      (P4P) programmes, yet little is known regarding their effects on continuity of
      care (COC) and the role of multiple chronic conditions (MCCs). This study aimed
      to examine the effects of a P4P programme for diabetes care on health care
      provision, COC and health care outcomes in diabetic patients with and without
      comorbid hypertension. METHODS: This study utilized a large-scale natural
      experiment with a 4-year follow-up period under a compulsory universal health
      insurance programme in Taiwan. The intervention groups consisted of patients with
      diabetes who were enrolled in the P4P programme in 2005. The comparison groups
      were selected via propensity score matching with patients who were seen by the
      same group of physicians. A difference-in-differences analysis was conducted
      using generalized estimating equation models to examine the effects of the P4P
      programme. RESULTS: Significant impacts were observed after the implementation of
      the P4P programme for diabetic patients with and without hypertension. The
      programme increased the number of necessary examinations/tests and improved the
      COC between patients and their physicians. The programme significantly reduced
      the likelihood of diabetes-related hospital admissions and emergency department
      visits [odds ratio (OR): 0.71; 95% confidence interval (CI): 0.63-0.80 for
      diabetic patients with hypertension; OR: 0.74; 95% CI: 0.64-0.86 for patients
      without hypertension]. However, the effects of the P4P programme diminished to
      some extent in the second year after its implementation. CONCLUSION: This study
      suggests that a financial incentive programme may improve the provision of
      necessary health care, COC and health care outcomes for diabetic patients both
      with and without comorbid hypertension. Health authorities could develop policies
      to increase participation in P4P programmes and encourage continued improvement
      in health care outcomes.

PMID- 25944705
TI  - Prices and mark-ups on antimalarials: evidence from nationally representative
      studies in six malaria-endemic countries.
AB  - The private for-profit sector is an important source of treatment for malaria.
      However, private patients face high prices for the recommended treatment for
      uncomplicated malaria, artemisinin combination therapies (ACTs), which makes them
      more likely to receive cheaper, less effective non-artemisinin therapies (nATs).
      This study seeks to better understand consumer antimalarial prices by documenting
      and exploring the pricing behaviour of retailers and wholesalers. Using data
      collected in 2009-10, we present survey estimates of antimalarial retail prices,
      and wholesale- and retail-level price mark-ups from six countries (Benin,
      Cambodia, the Democratic Republic of Congo, Nigeria, Uganda and Zambia), along
      with qualitative findings on factors affecting pricing decisions. Retail prices
      were lowest for nATs, followed by ACTs and artemisinin monotherapies (AMTs).
      Retailers applied the highest percentage mark-ups on nATs (range: 40% in Nigeria
      to 100% in Cambodia and Zambia), whereas mark-ups on ACTs (range: 22% in Nigeria
      to 71% in Zambia) and AMTs (range: 22% in Nigeria to 50% in Uganda) were similar
      in magnitude, but lower than those applied to nATs. Wholesale mark-ups were
      generally lower than those at retail level, and were similar across antimalarial
      categories in most countries. When setting prices wholesalers and retailers
      commonly considered supplier prices, prevailing market prices, product
      availability, product characteristics and the costs related to transporting
      goods, staff salaries and maintaining a property. Price discounts were regularly
      used to encourage sales and were sometimes used by wholesalers to reward long
      term customers. Pricing constraints existed only in Benin where wholesaler and
      retailer mark-ups are regulated; however, unlicensed drug vendors based in open
      air markets did not adhere to the pricing regime. These findings indicate that
      mark-ups on antimalarials are reasonable. Therefore, improving ACT affordability
      would be most readily achieved by interventions that reduce commodity prices for
      retailers, such as ACT subsidies, pooled purchasing mechanisms and cost-effective
      strategies to increase the distribution coverage area of wholesalers.

PMID- 25944706
TI  - Characterization and utility of phages bearing peptides with affinity to porcine
      reproductive and respiratory syndrome virus nsp7 protein.
AB  - High-affinity peptides to porcine reproductive and respiratory syndrome virus
      (PRRSV) nonstructural protein (nsp) 7 were identified using phage-display
      technology. Five 12-amino-acid peptide sequences were identified after six rounds
      of biopanning. A putative CD##WC motif was found in two different consensus
      peptides borne by phages 4 and 5. The peptides borne by phages 4, 5, and 6 were
      synthesized for subsequent experiments, according to the results of the binding
      assays. Immunofluorescence assay revealed that all these peptides recognized nsp7
      in PRRSV-infected cells. Furthermore, the peptides demonstrated antiviral
      activities, with peptides 5 and 6 showing effective inhibition. Early peptide
      stimulation was associated with strong antiviral activity, and the inhibitory
      effects of the peptides were dose-dependent at 36 and 48 h post-infection.
      Peptide 5 was selected to detect the intracellular localization of nsp7 by
      confocal microscopy. This peptide had a similar effect to anti-nsp7 monoclonal
      antibody on nsp7. These results suggest that high-affinity peptides to PRRSV nsp7
      could mimic the potential of nsp7 antibody as a diagnostic reagent for virus
      detection. Moreover, the peptides selected in this study represented a
      potentially effective antiviral candidate to inhibit PRRSV.

PMID- 25944707
TI  - Iodine-129 in snow and seawater in the Antarctic: level and source.
AB  - Anthropogenic (129)I has been released to the environment in different ways and
      chemical species by human nuclear activities since the 1940s. These sources
      provide ideal tools to trace the dispersion of volatile pollutants in the
      atmosphere. Snow and seawater samples collected in Bellingshausen, Amundsen, and
      Ross Seas in Antarctica in 2011 were analyzed for (129)I and (127)I, including
      organic forms; it was observed that (129)I/(127)I atomic ratios in the Antarctic
      surface seawater ((6.1-13) * 10(-12)) are about 2 orders of magnitude lower than
      those in the Antarctic snow ((6.8-9.5) * 10(-10)), but 4-6 times higher than the
      prenuclear level (1.5 * 10(-12)), indicating a predominantly anthropogenic source
      of (129)I in the Antarctic environment. The (129)I level in snow in Antarctica is
      2-4 orders of magnitude lower than that in the Northern Hemisphere, but is not
      significantly higher than that observed in other sites in the Southern
      Hemisphere. This feature indicates that (129)I in Antarctic snow mainly
      originates from atmospheric nuclear weapons testing from 1945 to 1980;
      resuspension and re-emission of the fallout (129)I in the Southern Hemisphere
      maintains the (129)I level in the Antarctic atmosphere. (129)I directly released
      to the atmosphere and re-emitted marine discharged (129)I from reprocessing
      plants in Europe might not significantly disperse to Antarctica. 

PMID- 25944708
TI  - Design, Synthesis and Inhibitory Activity of Photoswitchable RET Kinase
      Inhibitors.
AB  - REarranged during Transfection (RET) is a transmembrane receptor tyrosine kinase
      required for normal development and maintenance of neurons of the central and
      peripheral nervous systems. Deregulation of RET and hyperactivity of the RET
      kinase is intimately connected to several types of human cancers, most notably
      thyroid cancers, making it an attractive therapeutic target for small-molecule
      kinase inhibitors. Novel approaches, allowing external control of the activity of
      RET, would be key additions to the signal transduction toolbox. In this work,
      photoswitchable RET kinase inhibitors based on azo-functionalized
      pyrazolopyrimidines were developed, enabling photonic control of RET activity.
      The most promising compound displays excellent switching properties and stability
      with good inhibitory effect towards RET in cell-free as well as live-cell assays
      and a significant difference in inhibitory activity between its two photoisomeric
      forms. As the first reported photoswitchable small-molecule kinase inhibitor, we
      consider the herein presented effector to be a significant step forward in the
      development of tools for kinase signal transduction studies with spatiotemporal
      control over inhibitor concentration in situ. 

PMID- 25944709
TI  - CCN2/CTGF expression via cellular uptake of BMP-1 is associated with reparative
      dentinogenesis.
AB  - OBJECTIVE: CCN family member 2/connective tissue growth factor (CCN2/CTGF) is
      known as an osteogenesis-related molecule and is thought to be implicated in
      tooth growth. Bone morphogenetic protein-1 (BMP-1) contributes to tooth
      development by the degradation of dentin-specific substrates as a
      metalloprotease. In this study, we demonstrated the correlations between
      CCN2/CTGF and BMP-1 in human carious teeth and the subcellular dynamics of BMP-1
      in human dental pulp cells. MATERIALS AND METHODS: Expression of CCN2/CTGF and
      BMP-1 in human carious teeth was analyzed by immunohistochemistry. BMP-1-induced
      CCN2/CTGF protein expression in primary cultures of human dental pulp cells was
      observed by immunoblotting. Intracellular dynamics of exogenously administered
      fluorescence-labeled BMP-1 were observed using confocal microscope. RESULTS:
      Immunoreactivities for CCN2/CTGF and BMP-1 were increased in odontoblast-like
      cells and reparative dentin-subjacent dental caries. BMP-1 induced the expression
      of CCN2/CTGF independently of protease activity in the cells but not that of
      dentin sialophosphoprotein (DSPP) or dentin matrix protein-1 (DMP-1). Exogenously
      added BMP-1 was internalized into the cytoplasm, and the potent dynamin inhibitor
      dynasore clearly suppressed the BMP-1-induced CCN2/CTGF expression in the cells.
      CONCLUSION: CCN2/CTGF and BMP-1 coexist beneath caries lesion and CCN2/CTGF
      expression is regulated by dynamin-related cellular uptake of BMP-1, which
      suggests a novel property of metalloprotease in reparative dentinogenesis.

PMID- 25944710
TI  - The Dutch national breeding programmes have developed to major globally operating
      companies.

PMID- 25944711
TI  - Comparing sensitivity and specificity of screening mammography in the United
      States and Denmark.
AB  - Delivery of screening mammography differs substantially between the United States
      (US) and Denmark. We evaluated whether there are differences in screening
      sensitivity and specificity. We included screens from women screened at age 50-69
      years during 1996-2008/2009 in the US Breast Cancer Surveillance Consortium
      (BCSC) (n = 2,872,791), and from two population-based mammography screening
      programs in Denmark (Copenhagen, n = 148,156 and Funen, n = 275,553). Women were
      followed-up for 1 year. For initial screens, recall rate was significantly higher
      in BCSC (17.6%) than in Copenhagen (4.3%) and Funen (3.1%). Sensitivity was
      fairly similar in BCSC (91.8%) and Copenhagen (90.5%) and Funen (92.5%). At
      subsequent screens, recall rates were 8.8%, 1.8% and 1.4% in BCSC, Copenhagen and
      Funen, respectively. The BCSC sensitivity (82.3%) was lower compared with that in
      Copenhagen (88.9%) and Funen (86.9%), but when stratified by time since last
      screen, the sensitivity was similar. For both initial and subsequent screenings,
      the specificity of screening in BCSC (83.2% and 91.6%) was significantly lower
      than that in Copenhagen (96.6% and 98.8%) and Funen (97.9% and 99.2%). By taking
      time since last screen into account, it was found that American and Danish women
      had the same probability of having their asymptomatic cancers detected at
      screening. However, the majority of women free of asymptomatic cancers
      experienced more harms in terms of false-positive findings in the US than in
      Denmark.

PMID- 25944713
TI  - Pancreatic Calculus Causing Biliary Obstruction: Endoscopic Therapy for a Rare
      Initial Presentation of Chronic Pancreatitis.
AB  - INTRODUCTION: Biliary obstruction in chronic calcific pancreatitis (CCP) is often
      caused by inflammatory or fibrotic strictures of the bile duct, carcinoma of head
      of pancreas or less commonly by compression from pseudocysts. Pancreatic calculi
      causing ampullary obstruction and leading to obstructive jaundice is extremely
      rare. METHODS: The medical records of all patients with CCP or biliary
      obstruction who underwent endoscopic retrograde cholangiopancreatography (ERCP)
      over 4 years between 2010-2014 at Kasturba Medical College, Manipal were
      analyzed. RESULTS: Five patients of CCP with impacted pancreatic calculi at the
      ampulla demonstrated during ERCP were identified. All 5 presented with biliary
      obstruction and were incidentally detected to have CCP when evaluated for the
      same; 3 patients had features of cholangitis. All the patients were managed
      successfully by endoscopic papillotomy and extraction of pancreatic calculi from
      the ampulla with resolution of biliary obstruction. CONCLUSION: Pancreatic
      calculus causing ampullary obstruction, though very rare, should be considered as
      a possibility in patients with CCP complicated by biliary obstruction. Endoscopic
      therapy is affective in the resolution of biliary obstruction in such patients.

PMID- 25944712
TI  - N-terminome analysis of the human mitochondrial proteome.
AB  - The high throughput characterization of protein N-termini is becoming an emerging
      challenge in the proteomics and proteogenomics fields. The present study
      describes the free N-terminome analysis of human mitochondria-enriched samples
      using trimethoxyphenyl phosphonium (TMPP) labelling approaches. Owing to the
      extent of protein import and cleavage for mitochondrial proteins, determining the
      new N-termini generated after translocation/processing events for mitochondrial
      proteins is crucial to understand the transformation of precursors to mature
      proteins. The doublet N-terminal oriented proteomics (dN-TOP) strategy based on a
      double light/heavy TMPP labelling has been optimized in order to improve and
      automate the workflow for efficient, fast and reliable high throughput N
      terminome analysis. A total of 2714 proteins were identified and 897 N-terminal
      peptides were characterized (424 N-alpha-acetylated and 473 TMPP-labelled
      peptides). These results allowed the precise identification of the N-terminus of
      693 unique proteins corresponding to 26% of all identified proteins. Overall, 120
      already annotated processing cleavage sites were confirmed while 302 new cleavage
      sites were characterized. The accumulation of experimental evidence of mature N
      termini should allow increasing the knowledge of processing mechanisms and
      consequently also enhance cleavage sites prediction algorithms. Complete datasets
      have been deposited to the ProteomeXchange Consortium with identifiers PXD001521,
      PXD001522 and PXD001523
      (http://proteomecentral.proteomexchange.org/dataset/PXD001521,
      http://proteomecentral.proteomexchange.org/dataset/PXD0001522 and
      http://proteomecentral.proteomexchange.org/dataset/PXD001523, respectively). 

PMID- 25944714
TI  - Decreased PD-1/PD-L1 Expression Is Associated with the Reduction in Mucosal
      Immunoglobulin A in Mice with Intestinal Ischemia Reperfusion.
AB  - BACKGROUND: Intestinal ischemia/reperfusion (I/R) disrupts intestinal mucosal
      integrity and immunoglobulin A (IgA) generation. It has recently been shown that
      the programmed cell death-1 receptor (PD-1) plays a crucial role in regulating
      intestinal secreted IgA (sIgA). AIMS: To evaluate changes in PD-1 and PD-ligand 1
      (PD-L1) expression on Peyer's patches (PP) CD4(+) T cells and to investigate the
      correlation between PD-1/PD-L1 and intestinal IgA production/mucosal integrity in
      mice following intestinal I/R. METHODS: I/R injury was induced by clamping the
      superior mesenteric artery for 1 h followed by 2-h reperfusion. PD-1/PD-L1
      expression on PP CD4(+) T cells was measured in I/R and sham-operated mice.
      Additionally, transforming growth factor-beta1 (TGF-beta1) and interleukin-21 (IL
      21) mRNA in CD4(+) T cells and IgA(+) and IgM(+) in PP B cells, as well as
      intestinal mucosal injury and sIgA levels, were assessed. RESULTS: PD-1/PD-L1,
      TGF-beta1, and IL-21 expression was down-regulated after intestinal I/R.
      Furthermore, IgA(+) B cells decreased and IgM(+) B cells increased in mice with
      intestinal I/R. Importantly, decreased PD-1/PD-L1 expression was correlated with
      increased mucosal injury and decreased IgA levels, as well as with decreased TGF
      beta1 and IL-21 expression. CONCLUSIONS: Intestinal I/R inhibits PD-1/PD-L1
      expression on PP CD4(+) T cells, which was associated with an impaired intestinal
      immune system and mechanical barriers. Our study indicates that PD-1/PD-L1
      expression on CD4(+) T cells may be involved in the pathogenesis of intestinal
      I/R injury.

PMID- 25944715
TI  - Ursolic acid increases energy expenditure through enhancing free fatty acid
      uptake and beta-oxidation via an UCP3/AMPK-dependent pathway in skeletal muscle.
AB  - SCOPE: Ursolic acid (UA) is a triterpenoid compound with multifold biological
      functions. Our previous studies have reported that UA protects against high-fat
      diet-induced obesity and improves insulin resistance (IR). However, the potential
      mechanisms are still undefined. Free fatty acid (FFA) metabolism in skeletal
      muscle plays a central role in obesity and IR. Therefore, in this study, we
      investigated the effect and the potential mechanisms of UA on skeletal muscle FFA
      metabolism. METHODS AND RESULTS: In diet-induced obese rats, 0.5% UA
      supplementation for 6 weeks markedly reduced body weight, increased energy
      expenditure, decreased FFA level in serum and skeletal muscle and triglyceride
      content in skeletal muscle. In vitro, the data provided directly evidence that UA
      significantly increased fluorescently labeled FFA uptake and (3) H-labeled
      palmitic acid beta-oxidation. UA-activated AMP-activated protein kinase (AMPK)
      and downstream targets were involved in the increase of FFA catabolism. Moreover,
      upregulated uncoupling protein 3 (UCP3) by UA contributed to AMPK activation via
      elevating adenosine monophosphate/adenosine triphosphate ratio. CONCLUSION: UA
      increases FFA burning through enhancing skeletal muscle FFA uptake and beta
      oxidation via an UCP3/AMPK-dependent pathway, which provides a novel perspective
      on the biological function of UA against obesity and IR.

PMID- 25944716
TI  - The detection and discrimination of human body fluids using ATR FT-IR
      spectroscopy.
AB  - Blood, saliva, semen and vaginal secretions are the main human body fluids
      encountered at crime scenes. Currently presumptive tests are routinely utilised
      to indicate the presence of body fluids, although these are often subject to
      false positives and limited to particular body fluids. Over the last decade more
      sensitive and specific body fluid identification methods have been explored, such
      as mRNA analysis and proteomics, although these are not yet appropriate for
      routine application. This research investigated the application of ATR FT-IR
      spectroscopy for the detection and discrimination of human blood, saliva, semen
      and vaginal secretions. The results demonstrated that ATR FT-IR spectroscopy can
      detect and distinguish between these body fluids based on the unique spectral
      pattern, combination of peaks and peak frequencies corresponding to the
      macromolecule groups common within biological material. Comparisons with known
      abundant proteins relevant to each body fluid were also analysed to enable
      specific peaks to be attributed to the relevant protein components, which further
      reinforced the discrimination and identification of each body fluid. Overall,
      this preliminary research has demonstrated the potential for ATR FT-IR
      spectroscopy to be utilised in the routine confirmatory screening of biological
      evidence due to its quick and robust application within forensic science. 

PMID- 25944717
TI  - Day surgery versus overnight stay laparoscopic cholecystectomy: A systematic
      review and meta-analysis.
AB  - BACKGROUND: Laparoscopic cholecystectomies are being increasingly performed as a
      day surgery procedure. AIM: To systematically assess the safety and efficacy of
      laparoscopic cholecystectomy as a day surgery procedure compared to overnight
      stay. METHODS: Randomized controlled trials and clinical controlled trials
      involving day surgery laparoscopic cholecystectomy were included in a systematic
      literature search. Two authors independently assessed the studies for inclusion
      and extracted the data. A meta-analysis was conducted to estimate the safety and
      feasibility of day surgery compared to overnight stay laparoscopic
      cholecystectomy. RESULTS: Twelve studies were selected for our meta-analysis. The
      meta-analysis showed that there was no significant difference between the two
      groups on morbidity (P=0.65). The mean in-hospital admission and readmission
      rates were 13.1% and 2.4% in the day surgery group, respectively. The two groups
      had similar prolonged hospitalization (P=0.27), readmission rate (P=0.58) and
      consultation rate (P=0.73). In addition, there was no significant difference in
      the visual analogue scale score, postoperative nausea and vomiting scale, time to
      return to activity and work between the two groups (P>0.05). CONCLUSIONS:
      Currently available evidence demonstrates that laparoscopic cholecystectomy can
      be performed safely in selected patients as a day surgery procedure, though
      further studies are needed.

PMID- 25944719
TI  - Differential Distortion of Purine Substrates by Human and Plasmodium falciparum
      Hypoxanthine-Guanine Phosphoribosyltransferase to Catalyse the Formation of
      Mononucleotides.
AB  - Plasmodium falciparum (Pf) hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
      is a potential therapeutic target. Compared to structurally homologous human
      enzymes, it has expanded substrate specificity. In this study, 9-deazapurines are
      used as in situ probes of the active sites of human and Pf HGPRTs. Through the
      use of these probes it is found that non-covalent interactions stabilise the pre
      transition state of the HGPRT-catalysed reaction. Vibrational spectra reveal that
      the bound substrates are extensively distorted, the carbonyl bond of nucleobase
      moiety is weakened and the substrate is destabilised along the reaction
      coordinate. Raman shifts of the human and Pf enzymes are used to quantify the
      differing degrees of hydrogen bonding in the homologues. A decreased Raman cross
      section in enzyme-bound 9-deazaguanine (9DAG) shows that the phenylalanine
      residue (Phe186 in human and Phe197 in Pf) of HGPRT stacks with the nucleobase.
      Differential loss of the Raman cross-section suggests that the active site is
      more compact in human HGPRT as compared to the Pf enzyme, and is more so in the
      phosphoribosyl pyrophosphate (PRPP) complex 9DAG-PRPP-HGPRT than in 9
      deazahypoxanthine (9DAH)-PRPP-HGPRT. 

PMID- 25944718
TI  - Upregulation of SYF2 Relates to Retinal Ganglion Cell Apoptosis and Retinal Glia
      Cell Proliferation After Light-Induced Retinal Damage.
AB  - SYF2 (SYF2 homologue, RNA splicing factor), also known as CCNDBP1-interactor or
      p29, belongs to the SYF2 family, which are involved in pre-mRNA splicing and cell
      cycle progression. Accumulating evidences demonstrate that SYF2 exerted multiple
      effects including pro-apoptosis, cell differentiation, and glial activation in
      the pathogenesis of various experimental central nervous system (CNS) diseases.
      However, SYF2 expression and functions in the retina are still with limited
      acquaintance. To investigate whether SYF2 was involved in retinal degeneration,
      we performed a light-induced retinal damage model in adult rats. The SYF2 protein
      expression was dramatically upregulated after retinal damage. Besides that, SYF2
      localized in the retinal ganglion cell (RGC) layer (GCL), inner unclear layer
      (INL), and outer nuclear layer (ONL) after light exposure. In addition, the
      expression of cyclin D1, CDK4, and active caspase-3 was parallel with SYF2. We
      also found the co-localization of SYF2 with active caspase-3, PCNA, and CD11b.
      Collectively, SYF2 might participate in RGC apoptosis and retinal glia cell
      proliferation after light-induced retinal damage. 

PMID- 25944720
TI  - Molecular characterization and antimicrobial susceptibilities of Clostridium
      difficile clinical isolates from Victoria, Australia.
AB  - Some Australian strain types of Clostridium difficile appear unique, highlighting
      the global diversity of this bacterium. We examined recent and historic local
      isolates, finding predominantly toxinotype 0 strains, but also toxinotypes V and
      VIII. All isolates tested were susceptible to vancomycin and metronidazole, while
      moxifloxacin resistance was only detected in recent strains. 

PMID- 25944721
TI  - Current challenges to urological training in sub-Saharan Africa.

PMID- 25944722
TI  - AMPA receptor activation causes preferential mitochondrial Ca2+ load and
      oxidative stress in motor neurons.
AB  - It is well established that motor neurons are highly vulnerable to glutamate
      induced excitotoxicity. The selective vulnerability of these neurons has been
      attributed to AMPA receptor mediated excessive rise in cytosolic calcium and
      consequent mitochondrial Ca(2+) loading. Earlier we have reported that in motor
      neurons a generic rise in [Ca(2+)]i does not always lead to mitochondrial Ca(2+)
      loading and membrane depolarization but it occurs upon AMPA receptor activation.
      The mechanism of such specific mitochondrial involvement upon AMPA receptor
      activation is not known. The present study examines the mitochondrial Ca(2+)
      regulation and oxidative stress in spinal cord neurons upon AMPA subtype of
      glutamate receptor activation. Stimulating the spinal neurons with AMPA exhibited
      a sharp rise in [Ca(2+)]m in both motor and other spinal neurons that was
      sustained up to the end of recording time of 30min. The rise in [Ca(2+)]m was
      substantially higher in motor neurons than in other spinal neurons which could be
      due to the differential mitochondrial homeostasis in two types of neurons. To
      examine this possibility, we measured AMPA induced [Ca(2+)]m loading in the
      presence of mitochondrial inhibitors. In both cell types the AMPA induced
      [Ca(2+)]m loading was blocked by mitochondrial calcium uniporter blocker
      ruthenium red. In motor neurons it was also inhibited substantially by CGP37157
      and cyclosporine-A, the blockers of Na(+)/Ca(2+) exchanger and mitochondrial
      permeability transition pore (MPTP) respectively, whereas no effect of these
      agents was observed in other spinal neurons. Thus in motor neurons the Ca(2+)
      sequestration by mitochondria occurs through mitochondrial calcium uniporter as
      well as due to reversal of Na(+)/Ca(2+) exchanger, in contrast the latter pathway
      does not contribute in other spinal neurons. The ROS formation was inhibited by
      nitric oxide synthase (NOS) inhibitor L-NAME in both types of neurons, however
      the mitochondrial complex-I inhibitor rotenone suppressed the ROS formation only
      in motor neurons. It appears that activation of cytoplasmic nNOS leads to ROS
      formation in both types of spinal neurons but mitochondria is the major source of
      ROS in motor neurons. Spinal neurons exhibited a significant time dependent fall
      in glutathione (GSH) level. The GSH level in motor neurons did not recover even
      at 24h after AMPA exposure, whereas the other spinal neurons exhibited a tendency
      to maintain the GSH after a certain level suggesting that the oxidative stress is
      arrested in other spinal neurons but it continues to increase in motor neurons.
      Thus our results demonstrate that upon AMPA receptor stimulation the motor
      neurons employ some additional pathways for regulation of mitochondrial calcium
      and oxidative stress as compared to other spinal neurons. It is suggested that
      such differential signaling mechanisms in motor neurons could be crucial for
      their selective vulnerability to excitotoxicity. 

PMID- 25944723
TI  - Estimating the frequency of Candida in oral squamous cell carcinoma using
      Calcofluor White fluorescent stain.
AB  - OBJECTIVE: To determine the frequency of Candida in oral squamous cell carcinoma
      (OSCC) using Calcofluor White (CFW) fluorescent stain and to evaluate the
      association of the same in different grades of OSCC. METHODS: One hundred
      archival formalin fixed paraffin embedded tissues of diagnosed cases of OSCC were
      retrieved. The samples comprised of 81, 18 and 1 case of well, moderately, and
      poorly differentiated squamous cell carcinomas (WSCC, MSCC, PSCC) respectively.
      Each section was subjected to staining with CFW fluorescent stain for the
      detection of frequency of candidal hyphae. A chi square test was used to compare
      the proportion of occurrence of candidal hyphae between different grades of OSCC.
      RESULTS: Ten of the 100 cases of OSCCs stained positive for Candida with CFW.
      Positive staining for Candida was seen in six out of 81 and four out of 18 cases
      of WSCCs and MSCCs respectively. The chi square test used for comparison of the
      proportion of occurrence of candidal hyphae between WSCC and MSCC (P = 0.059) and
      all grades of OSCC (P = 0.157) did not yield any statistically significant value.
      CONCLUSION: The presence of Candida in OSCC solely does not justify its role in
      carcinogenesis. Further appraisal to evaluate a direct causal role of the micro
      organism in potentially malignant disorders and OSCC is required.

PMID- 25944724
TI  - Effective treatment of Bing-Neel Syndrome with oral fludarabine: a case series of
      four consecutive patients.

PMID- 25944725
TI  - MEPs call for new alcohol strategy and calorie display on labels.

PMID- 25944726
TI  - Control of the spread of viruses in a long-term care facility using hygiene
      protocols.
AB  - BACKGROUND: Approximately 50% of norovirus cases in the United States occur in
      long-term care facilities; many incidences of rotavirus, sapovirus, and
      adenovirus also occur. The primary objectives of this study were to demonstrate
      movement of pathogenic viruses through a long-term care facility and to determine
      the impact of a hygiene intervention on viral transmission. METHODS: The
      coliphage MS-2 was seeded onto a staff member's hands, and samples were collected
      after 4 hours from fomites and hands. After 3 consecutive days of sample
      collection, a 14-day hygiene intervention was implemented. Hand sanitizers, hand
      and face wipes, antiviral tissues, and a disinfectant spray were distributed to
      employees and residents. Seeding and sampling were repeated postintervention.
      RESULTS: Analysis of the pre- and postintervention data was performed using a
      Wilcoxon signed-rank test. Significant reductions in the spread of MS-2 on hands
      (P = .0002) and fomites (P = .04) were observed postintervention, with a >99%
      average reduction of virus recovered from both hands and fomites. CONCLUSION:
      Although MS-2 spread readily from hands to fomites and vice versa, the
      intervention reduced average MS-2 concentrations recovered from hands and fomites
      by up to 4 logs and also reduced the incidence of MS-2 recovery.

PMID- 25944727
TI  - Analysis of residual stress and hardness in regions of pre-manufactured and
      manual bends in fixation plates for maxillary advancement.
AB  - The aim of this study was to analyze, through Vickers hardness test and
      photoelasticity analysis, pre-bent areas, manually bent areas, and areas without
      bends of 10-mm advancement pre-bent titanium plates (Leibinger system). The work
      was divided into three groups: group I-region without bend, group II-region of 90
      degrees  manual bend, and group III-region of 90 degrees  pre-fabricated bends.
      All the materials were evaluated through hardness analysis by the Vickers
      hardness test, stress analysis by residual images obtained in a polariscope, and
      photoelastic analysis by reflection during the manual bending. The data obtained
      from the hardness tests were statistically analyzed using ANOVA and Tukey's tests
      at a significance level of 5 %. The pre-bent plate (group III) showed hardness
      means statistically significantly higher (P < 0.05) than those of the other
      groups (I-region without bends, II-90 degrees  manually bent region). Through the
      study of photoelastic reflection, it was possible to identify that the stress
      gradually increased, reaching a pink color (1.81 delta / lambda), as the bending
      was performed. A general analysis of the results showed that the bent plate
      region of pre-bent titanium presented the best results. 

PMID- 25944729
TI  - Cavited mass in a patient with sudden onset dyspnea.

PMID- 25944730
TI  - Clinical utility of a next generation sequencing panel assay for Marfan and
      Marfan-like syndromes featuring aortopathy.
AB  - Aortopathy can be defined as aortic dilation, aneurysm, dissection, and
      tortuosity. Familial aortopathy may occur secondary to fibrillin-1 (FBN1)
      mutations in the setting of Marfan syndrome, or may occur as a result of other
      genetic defects with different, but occasionally overlapping, phenotypes. Because
      of the phenotypic overlap and genetic heterogeneity of disorders featuring
      aortopathy, we developed a next generation sequencing (NGS) assay and comparative
      genomic hybridization (CGH) array to detect mutations in 10 genes that cause
      thoracic aortic aneurysms (TAAs). Here, we report on the clinical and molecular
      findings in 175 individuals submitted for aortopathy panel testing at ARUP
      laboratories. Ten genes associated with heritable aortopathies were targeted
      using hybridization capture prior to sequencing. NGS results were analyzed, and
      variants were confirmed using Sanger sequencing. Array CGH was used to detect
      copy-number variation. Of 175 individuals, 18 had a pathogenic mutation and 32
      had a variant of uncertain significance (VUS). Most pathogenic mutations (72%)
      were identified in FBN1. A novel large SMAD3 duplication and FBN1 deletion were
      identified. Over half who had TAAs or other aortic involvement tested negative
      for a mutation, suggesting that additional aortopathy genes exist. We anticipate
      that the clinical sensitivity of at least 10.3% will rise with VUS
      reclassification and as additional genes are identified and included in the
      panel. The aortopathy NGS panel aids in the timely molecular diagnosis of
      individuals with disorders featuring aortopathy and guides proper treatment.

PMID- 25944731
TI  - Efficacy of bisphosphonates against osteoporosis in adult men: a meta-analysis of
      randomized controlled trials.
AB  - This meta-analysis of published randomized controlled trials (RCTs) aimed to
      analyze the efficacy of administration of bisphosphonates in men with
      osteoporosis. Compared with placebo, bisphosphonates could reduce the risk of
      vertebral and non-vertebral fractures, reduce bone-specific alkaline phosphatase
      (BSAP) and C-terminal telopeptide of type I collagen (CTX), and increase bone
      mineral density (BMD). INTRODUCTION: Bisphosphonates are well-investigated
      antiresorptive medications, approved as first-line drugs for osteoporosis in
      postmenopausal women. However, there is a paucity of high-quality evidence
      regarding the efficacy of bisphosphonates administered for osteoporosis in adult
      men. The aim of this meta-analysis was to analyse the efficacy of administration
      of bisphosphonates in men based on published RCTs. METHODS: PubMed, Embase,
      MEDLINE, and the Cochrane library were searched, and mean differences were
      calculated to evaluate the efficacy of bisphosphonates on reducing the risk of
      vertebral and non-vertebral fracture, reducing bone-turnover biomarkers, and
      increasing BMD. RESULTS: Nine RCTs were included and the total number of
      participants was 2464. Compared with placebo, the efficacy of bisphosphonates on
      vertebral and non-vertebral fracture risk reduction was confirmed [for vertebral
      fracture, RR (95 % CI) 0.36 (0.24, 0.56), P < 0.01; for non-vertebral fracture,
      RR (95 % CI) 0.52 (0.32, 0.84), P < 0.01)] and heterogeneity was insignificant.
      The efficacy of bisphosphonates on reducing BSAP [MD (95 % CI) -24.41 (-26.19, 
      22.62), P < 0.01) and CTX [MD (95 % CI) -34.51 (-41.03, -27.98), P < 0.01)] was
      significant. A sensitivity analysis was applied to explain the origination of
      heterogeneity in analysis of decreasing of BSAP. BMD was increased in the
      bisphosphonates group compared with the control group at lumbar spine, femoral
      neck, and total hip (P < 0.01), and the heterogeneity of all comparisons was
      significant. CONCLUSION: Compared with placebo, bisphosphonates could decrease
      the risk of vertebral and non-vertebral fractures, reduce BSAP and CTX, and
      increase BMD in men with osteoporosis.

PMID- 25944732
TI  - High Hemoglobin Levels Maintained by an Erythropoiesis-Stimulating Agent Improve
      Renal Survival in Patients with Severe Renal Impairment.
AB  - Our goal was to investigate the effect modification of maintaining a high Hb
      target range through erythropoiesis-stimulating agent therapy on the renal
      outcome with respect to chronic kidney disease (CKD) stage and concurrent
      diabetes condition in patients with CKD. We used data from a previously reported
      randomized controlled trial involving 321 CKD patients not on dialysis, with Hb
      levels of <10 g/dL, and serum creatinine (Cr) of 2.0 to 6.0 mg/dL, and in which
      maintaining Hb levels at 11.0-13.0 g/dL with darbepoetin-alpha (High Hb group)
      resulted in a greater renal protective effect than maintaining Hb levels at 9.0
      11.0 g/dL with epoetin-alpha (Low Hb group). We conducted a post-hoc analysis of
      the effects of baseline CKD stage and concurrent diabetic condition on the renal
      composite endpoint, consisting of death, initiation of renal replacement therapy,
      and doubling of the serum Cr level. Both groups with stage 4 CKD had a 3-year
      cumulative renal survival rate of 53.8%, whereas in patients with stage 5 CKD,
      the rate in the High Hb group (31.0%) was significantly (P = 0.012) higher than
      that in the Low Hb group (19.1%). The observations made in patients with stage 5
      CKD were maintained on further analysis of non-diabetic patients, but were not
      seen in those with diabetes or stage 4 CKD. These results suggest that in
      patients with stage 5 CKD, especially those without diabetes, achieving a higher
      target Hb level with erythropoiesis-stimulating agents is associated with a
      greater renoprotective effect. 

PMID- 25944733
TI  - Intrathecal Clonidine via Lumbar Puncture Decreases Blood Pressure in Patients
      With Poorly Controlled Hypertension.
AB  - OBJECTIVES: Oral clonidine is used to treat hypertension but often produces
      sedation and severe dry mouth; intrathecal clonidine is used to treat chronic
      pain but may produce hypotension. This clinical feasibility study was conducted
      to determine if intrathecal clonidine decreases blood pressure in patients with
      poorly controlled hypertension. MATERIALS AND METHODS: This prospective, single
      arm, open-label study was conducted in ten subjects who were taking at least
      three antihypertensive medications including a diuretic and had an in-office
      systolic blood pressure between 140 and 190 mm Hg. On the day of treatment, blood
      pressure was measured before and after a single lumbar intrathecal dose (150 mcg)
      of clonidine using an automatic oscillometric device every 10-15 min for four
      hours. Student's paired t-test was used for statistical comparisons. RESULTS:
      Maximal reductions in systolic and diastolic blood pressures averaging 63 +/-
      20/29 +/- 13 mm Hg were observed approximately two hours after clonidine
      administration. Decreases in systolic pressure were strongly correlated with
      baseline systolic pressure. Clonidine produced a significant decrease in heart
      rate of 11 +/- 7 beats/min. No subject required intravenous fluids or vasopressor
      rescue therapy, or reported spinal headache. CONCLUSIONS: This is the first
      clinical study in subjects with hypertension that demonstrates significant and
      profound acute reductions in blood pressure after a single dose of intrathecal
      clonidine. Future placebo-controlled, dose-escalating studies are warranted to
      assess the long-term effects of intrathecal clonidine infusion via an implantable
      drug pump in patients with treatment-resistant hypertension at risk of stroke or
      myocardial infarction.

PMID- 25944734
TI  - Risk of Asthma in Late Preterm Infants: A Propensity Score Approach.
AB  - BACKGROUND: The risk of asthma, specifically in former late preterm infants, has
      not been well defined. Covariate imbalance and lack of controlling for this has
      led to inconsistent results in prior studies. OBJECTIVE: The objective of this
      study was to determine the risk of asthma in former late preterm infants using a
      propensity score approach. METHODS: The study was a population-based birth cohort
      study. Study subjects were all children born in Rochester, Minn, between 1976 and
      1982. Asthma status during the first 7 years of life was assessed by applying
      predetermined criteria. The propensity score was formulated using 15 covariates
      by fitting a logistic regression model for late preterm birth versus term birth.
      We applied the propensity score method to match late preterm infants (34 0/7 to
      36 6/7 weeks of gestation) to term infants (37 0/7 to 40 6/7 weeks of gestation)
      within a caliper of 0.2 standard deviation of logit of propensity score. RESULTS:
      Of the eligible 7040 infants, 5915 children had complete data. Before propensity
      score matching, late preterm infants had a higher risk of asthma (20 of 262,
      7.6%) compared with full-term infants (272 of 5653, 4.8%) (P = .039). There was
      significant covariate imbalance between comparison groups. After matching with
      propensity scores, we found that former late preterm infants had a similar risk
      of asthma to the matched full-term infants (6.6% vs 7.7%, respectively, P = .61),
      and the result was consistent with covariate-adjustment Cox regression models
      controlling for significant covariates (P = .57). CONCLUSION: A late preterm
      birth history is not independently associated with childhood asthma, as the
      reported risk of asthma among former late preterm infants appears to be due to
      covariate imbalance.

PMID- 25944735
TI  - Selection of empirical antibiotics for health care-associated pneumonia via
      integration of pneumonia severity index and risk factors of drug-resistant
      pathogens.
AB  - BACKGROUND/PURPOSE: The pneumonia severity index (PSI) both contains some risk
      factors of drug-resistant pathogens (DRPs) and represents the severity of health
      care-associated pneumonia. The aim of this study was to investigate whether the
      PSI could be used to predict DRPs and whether there were risk factors beyond the
      PSI. METHODS: A retrospective observational study enrolled 530 patients with
      health care-associated pneumonia who were admitted from January 2005 to December
      2010 in a tertiary care hospital. RESULTS: A total of 206 patients (38.9%) had
      DRPs, of which the most common was Pseudomonas aeruginosa (24.3%). The incidence
      of DRPs increased with increasing PSI classes (6.7%, 25.5%, 36.9%, and 44.6% in
      PSI II, III, IV, and V, respectively). An analysis of the risk factors for DRPs
      by PSI classes revealed that wound care was associated with methicillin-resistant
      Staphylococcus aureus (MRSA) infection in PSI V (p = 0.045). Nasogastric tube
      feeding (odds ratio, 3.88; 95% confidence interval, 1.75-8.60; p = 0.006), and
      bronchiectasis (odds ratio, 3.12; 95% confidence interval, 0.66-14.69; p = 0.007)
      were risk factors for DRPs in PSI III and IV. The area under the receiver
      operating characteristic curve progressed from 0.578 to 0.651 while integrating
      these risk factors with PSI classes. CONCLUSION: The findings suggested that PSI
      plus risk factors predicted the risk of DRPs. PSI II had a low risk of DRPs and
      could be treated as community-acquired pneumonia. Antibiotics of PSI III and IV
      with risk factors could be targeted DRPs. PSI V with wound care had a higher risk
      of MRSA, and empirical anti-MRSA antibiotics could be added.

PMID- 25944737
TI  - The evidence for rapid gametocyte viability changes in the course of parasitemia
      in Haemoproteus parasites.
AB  - Avian haemosporidian parasites of the genus Haemoproteus (Haemoproteidae,
      Haemosporida) are widespread, and some species cause diseases both in vertebrate
      hosts and blood-sucking insects. Parasitemia of Haemoproteus species usually is
      long-lasting, with gametocytes present in the circulation for several months.
      However, the viability of gametocytes and their ability to produce sexual cells
      have been insufficiently understood in the course of parasitemia. We initiated
      the sexual development in vitro conditions and calculated proportions of normal
      and anomalous ookinetes, which developed in two species of Haemoproteus. Mature
      gametocytes of the parasites were obtained from naturally infected avian hosts at
      different days of parasitemia. Haemoproteus (Parahaemoproteus) lanii (cytochrome
      b lineage hRB1) was isolated from one red-backed shrike Lanius collurio. Two
      isolates of Haemoproteus (Parahaemoproteus) tartakovskyi (cytochrome b lineage
      hSISKIN1) were used: one was obtained from a siskin Carduelis spinus and one from
      a common crossbill Loxia curvirostra. The wild-caught birds were kept indoors
      under controlled conditions, and blood was taken from them every 1 or 2 days
      during 10-14 days. After each blood sampling, the sexual process and ookinete
      development were initiated in vitro by exposure of infected blood containing
      mature gametocytes to air. Smears were prepared at intervals of 15 min, 3 h, and
      12 h after the exposure; they were examined microscopically. In all, 25
      experiments were performed; each experiment was repeated two times. The ratios of
      macro- and microgametocytes did not change in all experimental infections during
      this study. Sexual process occurred, and both normal and anomalous ookinetes
      developed in all parasites. The proportion of normal ookinetes did not change
      significantly in both isolates of H. tartakovskyi. Between 8 and 10 days of
      observation, the proportion of normal ookinetes of H. lanii decreased 6 times
      compared to the beginning of the experiment. That was accompanied with the rapid
      decrease of parasitemia and the inability of the majority of mature gametocytes
      to escape from erythrocytes and produce gametes, indicating disorder of the
      gametogenesis. There was clear difference in the gametogenesis between H.
      tartakovskyi and H. lanii from this point of view. This study shows that the
      viability of Haemoproteus gametocytes might change dramatically in the course of
      parasitemia within 1-2 days, and the presence of mature gametocytes in the
      circulation does not necessarily indicate their ability to exflagellate and
      produce ookinetes. We predict that this finding is important epidemiologically
      due to relationship with sporogony success.

PMID- 25944738
TI  - Interleukin-33 promotes Th2 immune responses in infected mice with Schistosoma
      japonicum.
AB  - IL-33, a new member of the IL-1 cytokine family, is associated with many
      infectious diseases. IL-33 not only is crucial for induction of Th2 polarized
      responses, but also is involved in induction of inflammation as a proinflammatory
      cytokine. Whether IL-33 leads to beneficial or worsening outcomes depends on the
      immune mechanism underlying the pathogensis of each disease condition. This study
      was to elucidate the role of IL-33 in schistosomiasis japonica in a mouse model.
      Our results demonstrated that serum levels of IL-33 from infected mice with
      Schistosoma japonicum began to rise at 1 week postinfection (pi) and reached a
      peak in 7 weeks pi, and then remained a plateau for 2 weeks, after which its
      level gradually decreased until 12 weeks pi. Compared with the infection control,
      exogenous IL-33 administration could increase a Th2 polarized immune response
      (evidenced by higher levels of IL-5, IL-10, and IL-13, along with lower level of
      IFN-gamma) at 6 weeks pi. Meanwhile, this Th2 polarization was associated with
      higher infection intensity and liver immunopathology in infected mice, whereas
      injection of anti-IL-33 mAb into infected mice induced adverse effects on these
      above immune parameters and immunopathology. These data suggest that IL-33 might
      act as an inducer of Th2 polarization and plays a crucial role in immunopathology
      in murine schistosomiasis japonica.

PMID- 25944736
TI  - (2-Hydroxypropyl)-beta-Cyclodextrin Is a New Angiogenic Molecule for Therapeutic
      Angiogenesis.
AB  - BACKGROUND: Peripheral artery disease (PAD), which is caused by atherosclerosis,
      results in progressive narrowing and occlusion of the peripheral arteries and
      inhibits blood flow to the lower extremities. Therapeutic angiogenesis is a
      promising strategy for treating ischemia caused by PAD. Nitric oxide (NO) has
      been shown to be a key mediator of angiogenesis. It has been demonstrated that
      beta-cyclodextrincan stimulate vessel growth in rabbit corneas. In this study, we
      assessed the mechanism of action and therapeutic potential of a new angiogenic
      molecule, (2-hydroxypropyl)-beta-cyclodextrin (2HP-beta-CD). METHODS AND RESULTS:
      2HP-beta-CD significantly increased vascular endothelial growth factor A (VEGF-A)
      and platelet-derived growth factor BB (PDGF-BB) peptides in human umbilical vein
      endothelial cells (HUVECs) and also increased basic fibroblast growth factor
      (bFGF) peptide in human aortic smooth muscle cells (HASMCs). 2HP-beta-CD
      stimulated both proliferation and migration of HUVECs in an endothelial nitric
      oxide synthase (eNOS)/NO-dependent manner, whereas NO was found to be involved in
      proliferation, but not migration, of HASMCs. In a unilateral hindlimb ischemia
      model in mice, 2HP-beta-CD injections not only promoted blood flow recovery and
      increased microvessel densities in ischemic muscle, but also promoted coverage of
      the vessels with smooth muscle cells, thus stabilizing the vessels.
      Administration of 2HP-beta-CD increased the expression of several angiogenic
      factors, including VEGF-A, PDGF-BB and transforming growth factor beta-1 (TGF
      beta1) in ischemic muscle. Injections of 2HP-beta-CD also stimulated protein
      kinase B and extracellular regulated protein kinases (ERK), leading to an
      increase in phosphorylation of eNOS in ischemic muscle. Treatment with the NOS
      inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME), showed that stimulation
      of blood flow induced by 2HP-beta-CD was partially dependent on NO. CONCLUSIONS:
      Therapeutic angiogenesis by 2HP-beta-CD may be beneficial to patients with PAD.

PMID- 25944739
TI  - Laboratory evaluation of efficacy and persistence of a 1% w/w fipronil pour-on
      formulation (Topline(r)) against Glossina palpalis gambiensis, Diptera:
      Glossinidae.
AB  - One zebu bull of 365 kg live weight was treated along the back line with 36 mL of
      fipronil as a pour-on formulation. Long-lasting mortalities of Glossina palpalis
      gambiensis were recorded despite exposure to sunlight and regular rinsing with 50
      L of water during the following 5 months. Significantly higher mortalities were
      still observed even 140, 170 and 190 days after treatment following their triple
      releases or triple feeding of caged tsetse on the treated bull. Mortalities of
      70, 80 and 44%, respectively, were recorded after 15 days of observation. This
      contrasted with the mortalities of control flies that were released in the
      presence of the untreated bull or fed in cages on the animal, amounting to 20 and
      twice 10% after 170 and 190 days. The feeding successes of the released or caged
      flies were higher than 95% and did not differ between control and experimental
      groups, indicating no repulsive or irritant effects of fipronil. The findings of
      this study are discussed, particularly in view of the potential of fipronil as an
      effective means for tsetse control.

PMID- 25944740
TI  - Mattesia weiseri sp. nov., a new neogregarine (Apicomplexa: Lipotrophidae)
      pathogen of the great spruce bark beetle, Dendroctonus micans (Coleoptera:
      Curculionidae, Scolytinae).
AB  - A new neogregarine pathogen of the great spruce bark beetle, Dendroctonus micans
      (Coleoptera: Curculionidae, Scolytinae), is described based on light microscopy
      and ultrastructural characteristics. The pathogen infects the fat body and the
      hemolymph of the beetle. The infection was nonsynchronous so that different
      developmental stages could be observed simultaneously in the hemolymph. All life
      stages from sporozoite to oocyst of the pathogen including micronuclear and
      macronuclear merozoites were detected. The sporozoites measured about 8.7 * 1.9
      MUm and trophozoites, 11.9 * 3.3 MUm. Micronuclear merozoites seen in the
      hemolymph were motile, elongate, slightly broader at the anterior pole, and
      measured 18.4 * 2.0 MUm. Macronuclear merozoites had a size of ca. 16.4 * 2.3
      MUm. Gametogamy results in the formation of two paired oocysts within a
      gametocyst. The lemon-shaped oocyst measured 10.9 * 6.1 MUm and had a very thick
      wall (375-450 nm). All morphological and ultrastructural characteristics of the
      life cycle stages indicate that the described neogregarine in D. micans is
      clearly different from known Mattesia species infecting bark beetles, and from
      any other described Mattesia spp. Therefore, we create a new species, Mattesia
      weiseri sp. nov.

PMID- 25944741
TI  - Interaction of carvacrol with the Ascaris suum nicotinic acetylcholine receptors
      and gamma-aminobutyric acid receptors, potential mechanism of antinematodal
      action.
AB  - Essential plant oils (or their active principles) are safe to use and a
      potentially attractive alternative to current antiparasitic drugs. In the present
      study, we tested the effects of carvacrol on the isolated tissues of Ascaris suum
      and investigated potential interactions with other antiparasitic drugs. We used
      somatic muscle flaps for contraction assays, as well as for electrophysiological
      investigations. Carvacrol 300 MUM highly significantly inhibited contractions
      caused by 1, 3, 10, 30, and 100 MUM of ACh (p = 0.0023, p = 0.0002, p = 0.0002, p
      < 0.0001, and p < 0.0001). The control EC50 for acetylcholine was 8.87 MUM (log
      EC50 = 0.95 +/- 0.26), while R max was 2.53 +/- 0.24 g. The EC50 of acetylcholine
      in the presence of 300 MUM of carvacrol was 27.71 MUM (log EC50 = 1.44 +/- 0.28)
      and the R max decreased to 1.63 +/- 0.32 g. Furthermore, carvacrol highly
      significant potentiates inhibitory effect of GABA and piperazine on the
      contractions induced by ACh. However, carvacrol (100 and 300 MUM), did not
      produce any changes in the membrane potential or conductance of the A. suum
      muscle cell. While, 300 MUM of carvacrol showed a significant inhibitory effect
      on ACh-induced depolarization response. The mean control depolarization was 13.58
      +/- 0.66 mV and decreased in presence of carvacrol to 4.50 +/- 1.02 mV (p <
      0.0001). Mean control Deltag was 0.168 +/- 0.017 MUS, while in the presence of
      300 MUM of carvacrol, Deltag significantly decreased to 0.060 +/- 0.018 DeltaS (p
      = 0.0017). The inhibitory effect on contractions may be the explanation of the
      antinematodal potential of carvacrol. Moreover, inhibition of depolarizations
      caused by ACh and reduction of conductance changes directly points to an
      interaction with the nAChR in A. suum.

PMID- 25944742
TI  - Generational differences in the sexual communication process of African American
      grandparent and parent caregivers of adolescents.
AB  - PURPOSE: This study assessed generational differences in the sexual communication
      process between 40 African American parent and 40 grandparent caregivers of
      adolescent children. DESIGN AND METHODS: The study reports findings from a
      secondary analysis of data from two databases. The HIV Risk Reduction Survey was
      used to examine the sexual communication process. RESULTS: Grandparents wanted to
      talk about sex and had open sexual communications, while parents valued sexual
      abstinence and had limited communications. PRACTICE IMPLICATIONS: Based on the
      findings, healthcare providers and programs need to recognize that differences do
      exist between parents and grandparents with sexual communications.

PMID- 25944743
TI  - Immunohistochemical study of Kruppel-like factor 4 in the spinal cords of rats
      with experimental autoimmune encephalomyelitis.
AB  - The expression and localization of Kruppel-like factor (KLF) 4, a class of zinc
      finger transcription factors, was investigated in the spinal cords of rats with
      experimental autoimmune encephalomyelitis (EAE) using western blotting and
      immunohistochemistry. KLF4 expression was increased significantly in EAE-affected
      spinal cords compared with normal rat spinal cords. The elevated levels of KLF4
      in the spinal cords of rats with EAE remained significant, even during the
      recovery stage of EAE. The cellular phenotype of KLF4 in EAE lesions consisted of
      some T cells, macrophages, and reactive astrocytes, whereas it was expressed
      constitutively in resting astrocytes and neurons, but not in ramified microglial
      cells in normal spinal cords. Collectively, we postulate that autoimmune T cells
      and macrophages activate KLF4 and subsequently do not proliferate or exhibit
      phenotypic switching from M1 to M2 macrophages, respectively. In addition, we
      hypothesize that the increased and sustained expression of KLF4 in reactive
      astrocytes during EAE was associated with suppressed CNS inflammation, as well as
      reduced numbers of pro-inflammatory T cells and M1 macrophages. 

PMID- 25944744
TI  - Structure-activity relationship of mastoparan analogs: Effects of the number and
      positioning of Lys residues on secondary structure, interaction with membrane
      mimetic systems and biological activity.
AB  - In this study, a series of mastoparan analogs were engineered based on the
      strategies of Ala and Lys scanning in relation to the sequences of classical
      mastoparans. Ten analog mastoparans, presenting from zero to six Lys residues in
      their sequences were synthesized and assayed for some typical biological
      activities for this group of peptide: mast cell degranulation, hemolysis, and
      antibiosis. In relation to mast cell degranulation, the apparent structural
      requirement to optimize this activity was the existence of one or two Lys
      residues at positions 8 and/or 9. In relation to hemolysis, one structural
      feature that strongly correlated with the potency of this activity was the number
      of amino acid residues from the C-terminus of each peptide continuously embedded
      into the zwitterionic membrane of erythrocytes-mimicking liposomes, probably due
      to the contribution of this structural feature to the membrane perturbation. The
      antibiotic activity of mastoparan analogs was directly dependent on the apparent
      extension of their hydrophilic surface, i.e., their molecules must have from four
      to six Lys residues between positions 4 and 11 of the peptide chain to achieve
      activities comparable to or higher than the reference antibiotic compounds. The
      optimization of the antibacterial activity of the mastoparans must consider Lys
      residues at the positions 4, 5, 7, 8, 9, and 11 of the tetradecapeptide chain,
      with the other positions occupied by hydrophobic residues, and with the C
      terminal residue in the amidated form. These requirements resulted in highly
      active AMPs with greatly reduced (or no) hemolytic and mast cell degranulating
      activities. 

PMID- 25944745
TI  - Retinal vein-to-vein anastomoses in Sturge-Weber syndrome documented by ultra
      widefield fluorescein angiography.
AB  - We report the case of a 6-year-old boy with Sturge-Weber syndrome and unilateral
      glaucoma in his left eye. He was born with a port wine mark involving his upper
      left eyelid. On ultra-widefield fluorescein angiography, he was found to have
      several vein-to-vein anastomoses in his left retina. To our knowledge, this is
      the first documentation of retinal vein-to-vein anastomoses in Sturge-Weber
      syndrome. 

PMID- 25944747
TI  - A crisis of visibility: The psychological consequences of false-positive
      screening mammograms, an interview study.
AB  - OBJECTIVE: To understand the meaning of having a false-positive screening
      mammogram. DESIGN: Qualitative interview study. METHODS: Twenty-one women, who
      had experienced false-positive screening mammograms, took part in semi-structured
      interviews that were analysed with Interpretive Phenomenological Analysis. This
      research took place in the United Kingdom. RESULTS: The analysis revealed a wide
      range of response to having a false-positive mammogram, from nonchalance to
      extreme fear. These reactions come from the potential for the belief that one is
      healthy to be challenged by being recalled, as the worst is frequently assumed.
      For most, the image of the lesion on the X-ray brought the reality of this
      challenge into sharp focus, as they might soon discover they had breast cancer.
      Waiting, whether for the appointment, at the clinic or for biopsy results was
      considered the worst aspect of being recalled. Generally, the uncertainty was
      quickly resolved with the pronouncement of the 'all-clear', which brought
      considerable relief and the restoration of belief in the healthy self. However,
      for some, lack of information, contradictory information, or poor interpersonal
      communication meant that uncertainty about their health status lingered at least
      until their next normal screening mammogram. Mammography screening related
      anxiety lasted for up to 12 years. CONCLUSION: Breast cancer screening produces a
      'crisis of visibility'. Accepting the screening invitation is taking a risk that
      you may experience unnecessary stress, uncertainty, fear, anxiety, and physical
      pain. Not accepting the invitation is taking a risk that malignant disease will
      remain invisible. Statement of contribution What is already known on this
      subject? More than 50,000 women a year in England have a false-positive mammogram
      (FPM). Having an FPM can cause anxiety compared with a normal mammogram. The
      anxiety can last up to 35 months. What does this study add? Refocuses attention
      from the average response found in quantitative studies to the wide range of
      individual response. Gives insight into the nature of the anxiety of having FPMs.
      Highlights the role of uncertainty in provoking distress from an FPM.

PMID- 25944746
TI  - Impact of Individualized Diet Intervention on Body Composition and Respiratory
      Variables in Children With Respiratory Insufficiency: A Pilot Intervention Study.
AB  - OBJECTIVES: Diet modification may improve body composition and respiratory
      variables in children with respiratory insufficiency. Our objective was to
      examine the effect of an individualized diet intervention on changes in weight,
      lean body mass, minute ventilation, and volumetric CO2 production in children
      dependent on long-term mechanical ventilatory support. DESIGN: Prospective, open
      labeled interventional study. SETTING: Study subjects' homes. PATIENTS: Children,
      1 month to 17 years old, dependent on at least 12 hr/d of transtracheal
      mechanical ventilatory support. INTERVENTIONS: Twelve weeks of an individualized
      diet modified to deliver energy at 90-110% of measured energy expenditure and
      protein intake per age-based guidelines. MEASUREMENTS AND MAIN RESULTS: During a
      multidisciplinary home visit, we obtained baseline values of height and weight,
      lean body mass percent by bioelectrical impedance analysis, actual energy and
      protein intake by food record, and measured energy expenditure by indirect
      calorimetry. An individualized diet was then prescribed to optimize energy and
      protein intake. After 12 weeks on this interventional diet, we evaluated changes
      in weight, height, lean body mass percent, minute ventilation, and volumetric CO2
      production. Sixteen subjects, mean age 9.3 years (SD, 4.9), eight male, completed
      the study. For the diet intervention, a majority of subjects required a change in
      energy and protein prescription. The mean percentage of energy delivered as
      carbohydrate was significantly decreased, 51.7% at baseline versus 48.2% at
      follow-up, p = 0.009. Mean height and weight increased on the modified diet. Mean
      lean body mass percent increased from 58.3% to 61.8%. Minute ventilation was
      significantly lower (0.18 L/min/kg vs 0.15 L/min/kg; p = 0.04), and we observed a
      trend toward lower volumetric CO2 production (5.4 mL/min/kg vs 5.3 mL/min/kg; p =
      0.06) after 12 weeks on the interventional diet. CONCLUSIONS: Individualized diet
      modification is feasible and associated with a significant decrease in minute
      ventilation, a trend toward significant reduction in CO2 production, and improved
      body composition in children on long-term mechanical ventilation. Optimization of
      respiratory variables and lean body mass by diet modification may benefit
      children with respiratory insufficiency in the ICU.

PMID- 25944748
TI  - Local adaptation of Gymnocypris przewalskii (Cyprinidae) on the Tibetan Plateau.
AB  - Divergent selection among environments affects species distributions and can lead
      to speciation. In this article, we investigated the transcriptomes of two
      ecotypes of scaleless carp (Gymnocypris przewalskii przewalskii and G. p.
      ganzihonensis) from the Tibetan Plateau. We used a transcriptome sequencing
      approach to screen approximately 250,000 expressed sequence tags (ESTs) from the
      gill and kidney tissues of twelve individuals from the Ganzi River and Lake
      Qinghai to understand how this freshwater fish has adapted to an ecological niche
      shift from saline to freshwater. We identified 9,429 loci in the gill
      transcriptome and 12,034 loci in the kidney transcriptome with significant
      differences in their expression, of which 242 protein-coding genes exhibited
      strong positive selection (Ka/Ks > 1). Many of the genes are involved in ion
      channel functions (e.g., Ca(2+)-binding proteins), immune responses (e.g.,
      nephrosin) or cellular water absorption functions (e.g., aquaporins). These
      results have potentially broad importance in understanding shifts from saline to
      freshwater habitats. Furthermore, this study provides the first transcriptome of
      G. przewalskii, which will facilitate future ecological genomics studies and aid
      in the identification of genes underlying adaptation and incipient ecological
      speciation. 

PMID- 25944749
TI  - Removal of heavy metals from tannery effluents of Ambur industrial area,
      Tamilnadu by Arthrospira (Spirulina) platensis.
AB  - The present study was carried out with the tannery effluent contaminated with
      heavy metals collected from Ambur industrial area to determine the
      phycoremediation potential of Arthrospira (Spirulina) platensis. Two different
      concentrations (50 and 100 %) of heavy metals containing tannery effluent treated
      with A. platensis were analysed for growth, absorption spectra, biochemical
      properties and antioxidant enzyme activity levels. The effluent treatments
      revealed dose-dependent decrease in the levels of A. platensis growth (65.37 %
      for 50 % effluent and 49.32 % for 100 % effluent), chlorophyll content (97.43 %
      for 50 % effluent and 71.05 % for 100 % effluent) and total protein content
      (82.63 % for 50 % effluent and 62.10 % for 100 % effluent) that leads to the
      reduction of total solids, total dissolved solids and total suspended solids. A.
      platensis with lower effluent concentration was effective than at higher
      concentration. Treatment with the effluent also resulted in increased activity
      levels of antioxidant enzymes, such as superoxide dismutase (14.58 units/g fresh
      weight for 50 % and 24.57 units/g fresh weight for 100 %) and catalase (0.963
      units/g fresh weight for 50 % and 1.263 units/g fresh weight for 100 %).
      Furthermore, heavy metal content was determined using atomic absorption
      spectrometry. These results indicated that A. platensis has the ability to combat
      heavy metal stress by the induction of antioxidant enzymes demonstrating its
      potential usefulness in phycoremediation of tannery effluent.

PMID- 25944750
TI  - Spatial prediction of landslide susceptibility in parts of Garhwal Himalaya,
      India, using the weight of evidence modelling.
AB  - Garhwal Himalaya in northern India has emerged as one of the most prominent hot
      spots of landslide occurrences in the Himalaya mainly due to geological causes
      related to mountain building processes, steep topography and frequent occurrences
      of extreme precipitation events. As this region has many pilgrimage and tourist
      centres, it is visited by hundreds of thousands of people every year, and in the
      recent past, there has been rapid development to provide adequate roads and
      building infrastructure. Additionally, attempts are also made to harness
      hydropower by constructing tunnels, dams and reservoirs and thus altering
      vulnerable slopes at many places. As a result, the overall risk due to landslide
      hazards has increased many folds and, therefore, an attempt was made to assess
      landslide susceptibility using 'Weights of Evidence (WofE)', a well-known
      bivariate statistical modelling technique implemented in a much improved way
      using remote sensing and Geographic Information System. This methodology has dual
      advantage as it demonstrates how to derive critical parameters related to
      geology, geomorphology, slope, land use and most importantly temporal landslide
      distribution in one of the data scarce region of the world. Secondly, it allows
      to experiment with various combination of parameters to assess their cumulative
      effect on landslides. In total, 15 parameters related to geology, geomorphology,
      terrain, hydrology and anthropogenic factors and 2 different landslide
      inventories (prior to 2007 and 2008-2011) were prepared from high-resolution
      Indian remote sensing satellite data (Cartosat-1 and Resourcesat-1) and were
      validated by field investigation. Several combinations of parameters were carried
      out using WofE modelling, and finally using best combination of eight parameters,
      76.5 % of overall landslides were predicted in 24 % of the total area susceptible
      to landslide occurrences. The study has highlighted that using such methodology
      landslide susceptibility assessment can be carried out in vast stretches of
      Himalaya in short time in order to assess the impact of development as well as
      climate change/variability. The resultant map can play a critical role in
      selecting areas for remedial measures for slope stabilisation as well planning
      for future development of the region.

PMID- 25944751
TI  - Changes in the dissolved organic matter leaching from soil under severe
      temperature and N-deposition.
AB  - In this study, we conducted growth chamber experiments using three types of soil
      (wetland, rice paddy, and forest) under the conditions of a severe increase in
      the temperature and N-deposition in order to investigate how extreme weather
      influences the characteristics of the dissolved organic matter (DOM) leaching
      from different soil types. This leachate controls the quantity and quality of DOM
      in surface water systems. After 5 months of incubation, the dissolved organic
      carbon (DOC) concentrations decreased in the range of 21.1 to 88.9 %, while the
      specific UV absorption (SUVA) values increased substantially in the range of 19.9
      to 319.9 % for all of the samples. Higher increases in the SUVA values were
      observed at higher temperatures, whereas the opposite trend was observed for
      samples with N-addition. The parallel factor analysis (PARAFAC) results showed
      that four fluorescence components: terrestrial humic-like (component 1 (C1)),
      microbial humic-like (component 2 (C2)), protein-like (component 3 (C3)), and
      anthropogenic humic-like (component 4 (C4)) constituted the fluorescence matrices
      of soil samples. During the experiment, labile DOM from the soils was consumed
      and transformed into resistant aromatic carbon structures and less biodegradable
      components via microbial processes. The principle component analysis (PCA)
      results indicated that severe temperatures and N-deposition could enhance the
      contribution of the aromatic carbon compounds and humic-like components in the
      soil samples.

PMID- 25944752
TI  - Hydrochemical diversity of semi-natural water system on the background of
      environmental conditions.
AB  - Research carried out from 2007 to 2011 showed that a tested semi-natural water
      system with a diverse catchment (peat, peat-mineral and mineral) has a very
      varied quality of water, as evidenced by a the large range of conductivity (174
      828 MUS/cm) and pH (6.34-9.92). Natural lake parts of the semi-natural water
      system were similar to the artificial parts in terms of physico-chemical
      parameters, as evidenced by the lack of statistically significant differences
      between the water quality in both of these ecosystems. Taking into account the
      quality of various types of water in this semi-natural system, it can be seen
      that the river waters differed significantly (p < 0.001) in concentrations of
      biogenic elements (nitrogen, phosphorus) from another type of ecosystems. In
      addition, rivers poor in organic matter (TOC < 10.0 mg/L) which directly supplied
      the water system contributed to higher values of many tested parameters (EC, pH,
      TC, TN, SO4 (2-) or Cl(-)) in waters of the canal. In contrast, rivers with high
      values of concentrations of organic matter (TOC > 10.0 mg/L) contributed to a
      decline in values of those parameters. Moreover, lake waters within the tested
      semi-natural water system showed a "cleansing" function, because they caused a
      decrease in conductivity, pH or the concentration of carbon, total nitrogen,
      sulphate(VI) and chloride in waters of the canal.

PMID- 25944753
TI  - Risk assessment of heavy metal contamination in sediments of a tropical lake.
AB  - The risk assessment of heavy metal contamination was carried out in sediments of
      an urban tropical lake system (Akkulam-Veli) under threat from rapid unplanned
      urbanization and poor sewage management. Heavy metals were selected due to their
      persistent and bioaccumulative nature. Sequential extraction of the metals was
      carried out to resolve the sediments to their component phases. Well-established
      models were employed for risk analysis. The two pathways of contamination
      ingestion and dermal contact-were considered for assessing risk. Risk Assessment
      Code of each metal was determined based on the lability of it in the different
      component phases. Cd was found to be the most hazardous metal by virtue of its
      high concentration in exchangeable and carbonate phases. Hazard indices of the
      metals were determined based on their total concentration in Akkulam-Veli (AV)
      Lake sediments. All heavy metals studied fall well below the threshold limit.
      However, Cr, Pb, and As, on account of their known toxicity, need to be
      monitored. Ni content in the lake system could potentially cause cancer to 134
      adults in a population of one million. Concentrations of other metals are at
      carcinogenically safe limits. The study stresses the looming hazard faced by the
      Akkulam-Veli Lake system by heavy metal contaminants and the urgency in
      formulating remedial management plans. 

PMID- 25944754
TI  - Pesticide residues in cereal crop grains in Poland in 2013.
AB  - This paper presents the results of the audit on pesticide residues in cereal
      grains throughout Poland in 2013. The number of all samples of cereal grains was
      380. Altogether 292 active substances of plant protection products were checked
      in the audit. Qualitative and quantative analyses were done according to Polish
      Standard PN-EN 15562:2008, using the LC-MS/MS technique. The methods (QuEChERS)
      is based on extraction of residues of plant protection products from a sample
      using acetonitrile. In the samples analyzed, 62 % of them did not contain any
      pesticide residues, 34 % of samples of cereal grains contained such residues but
      below the maximum residue limit, 3 % contained residues over the maximum limit,
      whereas 1 % of the samples contained illegal substances. The lowest amounts of
      pesticide residues were found in cereal grains coming from fields with cereal
      mixtures and in Avena grains, while the highest amounts were in Hordeum and
      Triticum grains. The substances found most often were fungicide residues. In
      northern and southern regions of Poland (Silesian, Pomeranian, and Kuyavian
      Pomeranian voivodeships), cereal grains with pesticide residues were much more
      common than in other regions of Poland.

PMID- 25944755
TI  - Pattern of multiresistant to antimicrobials and heavy metal tolerance in bacteria
      isolated from sewage sludge samples from a composting process at a recycling
      plant in southern Brazil.
AB  - The composting process is a viable alternative for the recycling of household
      organic waste and sewage sludge generated during wastewater treatment. However,
      this technique can select microorganisms resistant to antimicrobials and heavy
      metals as a result of excess chemicals present in compost windrow. This study
      evaluates the antimicrobial multiresistant and tolerance to heavy metals in
      bacteria isolated from the composting process with sewage sludge. Fourteen
      antimicrobials were used in 344 strains for the resistance profile and four heavy
      metals (chromium, copper, zinc, and lead) for the minimum biocide concentration
      assay. The strains used were from the sewage sludge sample (beginning of the
      process) and the compost sample (end of the process). Strains with higher
      antimicrobial and heavy metal profile were identified by 16S rRNA gene
      sequencing. The results showed a multiresistant profile in 48 % of the strains,
      with the highest percentage of strains resistant to nitrofurantoin (65 %) and
      beta-lactams (58 %). The strains isolated from the sewage sludge and the end of
      the composting process were more tolerant to copper, with a lethal dose of
      approximately 900 mg L(-1) for about 50 % of the strains. The genera that showed
      the highest multiresistant profile and increased tolerance to the metals tested
      were Pseudomonas and Ochrobactrum. The results of this study may contribute to
      future research and the revision and regulation of legislation on sewage sludge
      reuse in soils.

PMID- 25944756
TI  - Trace elements in two staple cereals (rice and wheat) and associated health risk
      implications in Bangladesh.
AB  - Concentrations of fourteen trace elements (Cd, As, Pb, Cr, Ni, Zn, Se, Cu, Mo,
      Mn, Sb, Ba, V and Ag) in the composite samples of most frequently consumed two
      staple foods, i.e. rice and wheat (collected from 30 different agroecological
      zones for the first time in Bangladesh) were measured by ICP-MS. The mean
      concentrations (mg/kg fresh weight) of Cd, As, Pb, Cr, Ni, Zn, Se, Cu, Mo, Mn,
      Sb, Ba, V and Ag were found as 0.088, 0.321, 0.713, 0.183, 0.213, 13.178, 0.0256,
      1.985, 0.102, 4.654, 0.0033, 0.144, 0.081 and 0.007 and 0.011, 0.281, 0.221,
      0.352, 0.145, 15.472, 0.245, 1.894, 0.209, 22.077, 0.0012, 3.712, 0.023 and
      0.0013 in rice and wheat samples, respectively. Dietary risk of human health (non
      carcinogenic and carcinogenic risks) was assessed by USEPA deterministic
      approaches. Total target hazard quotient (THQ) values for As and Pb were higher
      than 1, suggesting that people would experience significant health risks from
      consuming rice and wheat. However, the THQ of other metals were all less than 1.
      Also, the estimation showed that the target carcinogenic risk (TR) of As and Pb
      exceeded the accepted risk level of 1 * 10(-6). Moreover, concerning the
      nutritional requirements of essential elements for a sound health, the
      recommended doses for the daily intake of Mn was conveniently supplied by the
      studied cereals; however, Cr, Zn, Se, Cu and Mo were below the recommend daily
      allowances (RDAs). Thus, the carcinogenic and non-carcinogenic risk of As and Pb
      with lower supplementation of essential elements via staple foods for Bangladeshi
      people is a matter of concern.

PMID- 25944757
TI  - Pediatric transcatheter valve replacement: guests at our own table?

PMID- 25944758
TI  - Clinical and hemodynamic outcomes up to 7 years after transcatheter pulmonary
      valve replacement in the US melody valve investigational device exemption trial.
AB  - BACKGROUND: Studies of transcatheter pulmonary valve (TPV) replacement with the
      Melody valve have demonstrated good short-term outcomes, but there are no
      published long-term follow-up data. METHODS AND RESULTS: The US Investigational
      Device Exemption trial prospectively enrolled 171 pediatric and adult patients
      (median age, 19 years) with right ventricular outflow tract conduit obstruction
      or regurgitation. The 148 patients who received and were discharged with a TPV
      were followed up annually according to a standardized protocol. During a median
      follow-up of 4.5 years (range, 0.4-7 years), 32 patients underwent right
      ventricular outflow tract reintervention for obstruction (n=27, with stent
      fracture in 22), endocarditis (n=3, 2 with stenosis and 1 with pulmonary
      regurgitation), or right ventricular dysfunction (n=2). Eleven patients had the
      TPV explanted as an initial or second reintervention. Five-year freedom from
      reintervention and explantation was 76+/-4% and 92+/-3%, respectively. A conduit
      prestent and lower discharge right ventricular outflow tract gradient were
      associated with longer freedom from reintervention. In the 113 patients who were
      alive and reintervention free, the follow-up gradient (median, 4.5 years after
      implantation) was unchanged from early post-TPV replacement, and all but 1
      patient had mild or less pulmonary regurgitation. Almost all patients were in New
      York Heart Association class I or II. More severely impaired baseline spirometry
      was associated with a lower likelihood of improvement in exercise function after
      TPV replacement. CONCLUSIONS: TPV replacement with the Melody valve provided good
      hemodynamic and clinical outcomes up to 7 years after implantation. Primary valve
      failure was rare. The main cause of TPV dysfunction was stenosis related to stent
      fracture, which was uncommon once prestenting became more widely adopted.
      CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT00740870.

PMID- 25944759
TI  - Dieckol, a major phlorotannin in Ecklonia cava, suppresses lipid accumulation in
      the adipocytes of high-fat diet-fed zebrafish and mice: Inhibition of early
      adipogenesis via cell-cycle arrest and AMPKalpha activation.
AB  - SCOPE: Dieckol is a major polyphenol of Ecklonia cava. This study demonstrates a
      mechanistic role for dieckol in the suppression of lipid accumulation using three
      models. METHODS AND RESULTS: Mice were split into four experimental groups (n =
      10 per group): normal diet, high-fat diet (HFD), and dieckol-supplemented diets.
      Dieckol-supplemented mice groups showed a significant decrease of body weight
      gain (38%) as well as fats of organs including epididymal (45%) compared with a
      HFD-fed group. LDL cholesterol level was reduced by 55% in dieckol-supplemented
      group. Adipogenic factors and lipid synthetic enzymes were analyzed via real-time
      PCR or immunoblotting. Dieckol regulated mRNA expressions of early adipogenic
      genes in 3T3-L1 cells. These results were reflected in downregulation of late
      adipogenic factors, resulting in a decrease in triacylglycerol content. These
      data were also verified in zebrafish and mouse models. Dieckol activated AMP
      activated protein kinase alpha (AMPKalpha) signaling to inhibit lipid synthesis
      in 3T3-L1 and mouse model. Dieckol was also shown to inhibit mitotic clonal
      expansion via cell-cycle arrest. CONCLUSION: Our data demonstrate that dieckol
      inhibits lipid accumulation via activation of AMPKalpha signaling and cell-cycle
      arrest.

PMID- 25944760
TI  - Epilepsy phenotypes in siblings with Norrie disease.
AB  - Norrie disease is an X-linked recessive disorder that is characterized by
      congenital blindness. Although epileptic seizures are observed in some patients
      with Norrie disease, little is known about this phenomenon. Here, we report the
      manifestation of epilepsy in siblings with Norrie disease to increase our
      knowledge of epilepsy in this condition. Three brothers with congenital blindness
      were diagnosed with Norrie disease after genetic analyses indicated the deletion
      of exon 2 of the NDP gene. The eldest brother had suffered from epileptic
      seizures since the age of 11years, and his seizures were resistant to
      antiepileptic drugs. Although the second brother had no epileptic seizures, the
      youngest sibling had experiences epileptic seizures since the age of 8years. His
      seizures were controlled using lamotrigine and levetiracetam. An
      electroencephalography (EEG) revealed epileptiform discharges in the occipital
      areas in all three brothers. A study of these patients will increase our
      knowledge of epilepsy in patients with Norrie disease. 

PMID- 25944761
TI  - Merging perspectives: obstacles to recovery for youth from refugee backgrounds
      with comorbidity.
AB  - OBJECTIVE: This research aimed to identify challenges encountered by young people
      from refugee backgrounds with co-existing mental health (MH) and alcohol and
      other drug (AOD) problems (comorbidity) and sought to compare the perspectives of
      refugee youth and service providers in a metropolitan region of Adelaide, South
      Australia. METHODS: Semi-structured interviews were conducted with two groups of
      participants: young people from refugee backgrounds (African, Afghan, Bhutanese)
      and workers from MH, AOD and refugee support services. RESULTS: The refugee youth
      reported that the biggest difficulty they face once they develop MH and AOD
      problems is social disconnectedness. They lacked awareness that services are
      available to support them. In contrast, clinicians rated difficulty accessing and
      receiving culturally competent comorbidity care as the greatest challenge. Other
      reported challenges were relatively consistent across both groups. CONCLUSIONS:
      This study has implications for how we engage these young people in services,
      prioritise areas of care and effectively treat and support refugee youth
      experiencing comorbidity. These findings emphasise the need for a combined
      therapeutic casework approach, addressing needs such as social connectedness,
      housing, education and employment.

PMID- 25944762
TI  - The epidemiology of amphetamine type stimulant-related admissions in Albany,
      Western Australia: 2008-2013.
AB  - OBJECTIVE: To explore the epidemiology of amphetamine type stimulant (ATS)
      related admissions over six years in a regional centre, and to observe changes
      over time and compare demographics to national trends. METHOD: A retrospective
      audit of patients admitted with an International Classification of Diseases-10
      (ICD-10) code relating to ATS use from 2008 to 2013 at Albany Health Campus. Age,
      gender and reason for admission were compared across each year, including repeat
      presentations. Concomitant codes during admission were noted. RESULTS: One
      hundred and fifty two ATS-related hospital episodes were identified during the
      study period, 55% male and 45% female, with an age range from 16 to 50. Admission
      numbers increased over time. Patients with multiple admissions made up 35% of
      episodes. The most common reasons for admission were harmful use (F15.1) and
      psychotic disorder (F15.5). Sixty-nine percent of admissions had a concomitant
      ICD-10 code for mental health, 18% another medical code and 28% another factor
      influencing health status. CONCLUSION: The number of recognised ATS-related
      presentations is increasing at Albany Health Campus. A broad age range and
      comparatively high proportion of women were hospitalised. These patients have
      complex needs and many had multiple ATS-related admissions.

PMID- 25944763
TI  - The therapeutic use of postcards in a mental health support group.
AB  - OBJECTIVE: The aim of this project was to provide some group support for mental
      health patients in a general practice that employed a Mental Health Nurse
      Incentive Program nurse. METHOD: Group members were involved in the development
      of the group and in the setting of its rules and goals. Postcards were used to
      invite members to each meeting. RESULTS: No ill effects resulted from the use of
      postcards and they served as a valued way to recognize individuals within the
      group. CONCLUSION: This use of postcards proved therapeutic in unexpected ways
      and was very well accepted.

PMID- 25944764
TI  - Here and Now Aboriginal Assessment: background, development and preliminary
      evaluation of a culturally appropriate screening tool.
AB  - OBJECTIVE: Assessment of Aboriginal social and emotional wellbeing (SEWB) is a
      complex and challenging task, in part due to a lack of suitable assessment tools.
      This paper reports the development and evaluation of a culturally appropriate
      screening tool called the Here and Now Aboriginal Assessment (HANAA). METHOD: The
      initial phase included development of a glossary of Aboriginal terms and concepts
      relating to SEWB. The glossary was used to identify 10 key HANAA domains, which
      included physical health, sleep, mood, suicide risk and self harm, substance use,
      memory, unusual experiences, functioning, life stressors and resilience.
      Evaluation of the HANAA included exploration of its cultural applicability,
      feasibility, reliability and validity. RESULTS: The HANAA was well accepted by
      study participants and easily implemented by assessors. Reliability was good,
      with inter-rater agreements between Aboriginal and non-Aboriginal assessors
      measured by Kappa statistics ranging from 0.5 to 1.0. There was also a good
      agreement between assessors and treating clinicians in identifying the main
      presenting problem and recommended course of action. CONCLUSION: The HANAA is a
      culturally appropriate and useful tool for the screening of SEWB among Aboriginal
      adults. It can also be used for teaching and training purposes of mental health
      and other professionals working with Aboriginal people.

PMID- 25944765
TI  - Mentalization-based intervention to recurrent acute presentations and self-harm
      in a community mental health service setting.
AB  - OBJECTIVES: A proof-of-concept study over an 18-month period to determine whether
      a mentalization-based intervention (MBI) in a metropolitan community mental
      health service, when added to a recovery-based model of care, would be of
      clinical benefit to borderline personality disorder (BPD) consumers with a
      history of recurrent, deliberate self-harm. The feasibility of implementing the
      intervention, and factors that could improve its implementation, will be
      evaluated. METHODS: Three-monthly focus groups with participating community
      mental health service case managers (N = 8) assessed the implementation and the
      impact of an MBI added to a recovery model of care and the way the clinicians
      worked with consumers with BPD and recurrent, deliberate self-harm in this
      context. RESULTS: Qualitative analysis revealed compatibility of the MBI with a
      recovery-based case management approach for the above group of consumers, albeit
      with operational barriers. CONCLUSIONS: MBI with consumers with BPD appears to be
      compatible with recovery-focused psychiatric case management and was accepted by
      consumers. The case managers perceived that no harm was rendered in terms of
      deliberate self-harm and acute service utilization. The MBI led to a sense of
      improved therapeutic alliance in case managers working with consumers.

PMID- 25944766
TI  - Cloning and characterization of heterologous transporters in Saccharomyces
      cerevisiae and identification of important amino acids for xylose utilization.
AB  - Efficient and specific transporters may enhance pentose uptake and metabolism by
      Saccharomyces cerevisiae. Eight heterologous sugar transporters were
      characterized in S. cerevisiae. The transporter Mgt05196p from Meyerozyma
      guilliermondii showed the highest xylose transport activity among them. Several
      key amino acid residues of Mgt05196p were suggested by structural and sequence
      analysis and characterized by site-directed mutagenesis. A conserved aromatic
      residue-rich motif (YFFYY, position 332-336) in the seventh trans-membrane span
      plays an important role in D-xylose transport activity. The phenyl ring of the
      residue at position 336 may take the function to prevent D-xylose from escaping
      during uptake. F432A and N360S mutations enhanced the D-xylose transport
      activities of Mgt05196p. Furthermore, mutant N360F specifically transported D
      xylose without any glucose-inhibition, high lighting its potential application in
      constructing glucose-xylose co-fermentation strains for biomass refining.

PMID- 25944767
TI  - Extended use of dried-leukocytes impregnated in filter paper samples for
      detection of Pompe, Gaucher, and Morquio A diseases.
AB  - BACKGROUND: Lysosomal storage diseases (LSD) are a group of genetic conditions
      which could present a vast spectrum of abnormalities that may include skeletal
      abnormalities, organ dysfunction, neuronal involvement, and tissue accumulation
      of complex molecules, among other manifestations. Definitive diagnosis of LSD is
      generally obtained by specific enzyme assays performed in leukocytes,
      fibroblasts, or more recently, dried-blood filter paper (DBFP) samples. METHODS:
      We recently introduced dried-leukocytes filter paper (DLFP) as an alternative
      source of enzyme to assay heparan sulfamidase and galactocerebrosidase
      activities, which could not be measured in DBFP samples using fluorometric
      methods. We present a new fluorometric methods on DLFP samples, for evaluation of
      alpha-glucosidase (GAA), beta-glucosidase (GBA), and N-acetylgalactosamine-6
      sulfatase (GALNS) activities, key enzyme assays for the identification of
      patients with Pompe disease (PD), Gaucher disease (GD), and Morquio A disease
      (MD), respectively. RESULTS: We show a clear discrimination between confirmed PD,
      GD, and MD patients and healthy controls. CONCLUSIONS: We conclude that the
      assays of GAA, GBA, and GALNS on DLFP are reliable and useful methods for the
      identification of PD, GD, and MD diseases, respectively. As sample preparation is
      feasible in standard biochemical laboratories and transportation is very simple,
      it could enable patients living in remote areas to be investigated, diagnosed and
      eventually treated with the specific therapies available for these diseases.

PMID- 25944768
TI  - Evaluating diagnostic accuracy of anti-tissue Transglutaminase IgA antibodies as
      first screening for Celiac Disease in very young children.
AB  - BACKGROUND: Small bowel biopsy is the gold standard for Celiac Disease (CD)
      diagnosis, nevertheless serum assays are the first step in ascertaining a
      diagnosis of CD. New ESPGHAN Criteria 2012 (European Society of Pediatric
      Gastroenterology Hepatology and Nutrition) suggest using exclusively anti-tissue
      Transglutaminase IgA antibodies (anti-tTGA) as initial approach to symptomatic
      subjects. The aim of our study was to evaluate the diagnostic accuracy of anti
      tTGA as initial screening assay for CD in a large cohort of pediatric patients.
      METHODS: We selected 730 subjects aged between 6 months and 4 years ("Group A")
      and 348 subjects younger than 2 years (which are part of the 730 subjects)
      ("Group B"). We performed anti-Deamidated Gliadin Peptides IgA and IgG antibodies
      (a-DGP IgA/IgG) and anti-tTGA assays by ELISA test. We evaluated the agreement
      between anti-tTGA and a-DGP IgA/IgG assays and compared the diagnostic accuracy
      of a-DGP IgA/IgG with that of anti-tTGA in both groups of patients. RESULTS:
      There was a substantial agreement between anti-tTGA and a-DGP IgA in "Group A"
      and an almost perfect agreement in "Group B"; the strength of agreement between
      anti-tTGA and a-DGP IgG was moderate in "Group A" and substantial in "Group B".
      anti-tTGA were more sensitive and specific than a-DGP IgA/IgG in both groups.
      CONCLUSIONS: anti-tTGA could be used as initial screening assay for CD in all
      subjects from 6 months of age according to ESPGHAN Criteria 2012.

PMID- 25944769
TI  - The induction of pro-angiogenic processes within a collagen scaffold via
      exogenous estradiol and endometrial epithelial cells.
AB  - Nutrient transport remains a major limitation in the design of biomaterials. One
      approach to overcome this constraint is to incorporate features to induce
      angiogenesis-mediated microvasculature formation. Angiogenesis requires a
      temporal presentation of both pro- and anti-angiogenic factors to achieve stable
      vasculature, leading to increasingly complex biomaterial design scheme. The
      endometrium, the lining of the uterus and site of embryo implantation,
      exemplifies a non-pathological model of rapid growth, shedding, and re-growth of
      dense vascular networks regulated by the dynamic actions of estradiol and
      progesterone. In this study, we examined the individual and combined response of
      endometrial epithelial cells and human umbilical vein endothelial cells to
      exogenous estradiol within a three-dimensional collagen scaffold. While
      endothelial cells did not respond to exogenous estradiol, estradiol directly
      stimulated endometrial epithelial cell transduction pathways and resulted in dose
      dependent increases in endogenous VEGF production. Co-culture experiments using
      conditioned media demonstrated estradiol stimulation of endometrial epithelial
      cells can induce functional changes in endothelial cells within the collagen
      biomaterial. We also report the effect of direct endometrial epithelial and
      endothelial co-culture as well as covalent immobilization of estradiol within the
      collagen biomaterial. These efforts establish the suitability of an endometrial
      inspired model for promoting pro-angiogenic events within regenerative medicine
      applications. These results also suggest the potential for developing biomaterial
      based models of the endometrium.

PMID- 25944772
TI  - Of mice and cats (both calico): Mary F Lyon, FRS (1925-2014).

PMID- 25944770
TI  - Behavior of total and free serum testosterone as a predictor for the risk of
      prostate cancer and its aggressiveness.
AB  - CONTEXT: Serum testosterone is mostly bound to the sex hormone-binding globulin
      and albumin. A small metabolically active part is present in the form of free
      testosterone (FT). The relationship between serum total testosterone (TT) levels
      and prostate carcinogenesis is debated. Our hypothesis is that the serum FT
      concentration is more closely associated with the risk of prostate cancer (PC)
      and its aggressiveness than TT. OBJECTIVE: To analyze the scientific evidence
      that relates serum TT and/or FT levels with the diagnosis of PC and its
      aggressiveness. ACQUISITION OF EVIDENCE: A systematic review was conducted in
      PubMed up to January 2015 using the following mesh terms: prostate cancer, sex
      hormone, androgen, testosterone and free testosterone. SYNTHESIS OF THE EVIDENCE:
      We found 460 publications, 124 of which were reviewed to analyze the evidence.
      The relationship between serum TT levels and the diagnosis of PC and its
      aggressiveness is highly heterogeneous. The variability in the design of the
      studies, the quantification methods and other variables could explain this
      heterogeneity. In a number of studies that evaluated the estimated or measured
      FT, the evidence remains equally conflicting. CONCLUSIONS: Based on the current
      evidence, we cannot recommend the measurement of serum TT and/or TL levels for
      the diagnosis of PC or for assessing its aggressiveness.

PMID- 25944771
TI  - Usefulness of procalcitonin and C-reactive protein for predicting bacteremia in
      urinary tract infections in the emergency department.
AB  - INTRODUCTION: The aim of this study was to analyze and compare the capacity of
      procalcitonin (PCT), C-reactive protein (CRP), lactate and leukocytes to predict
      the presence of bacteremia in patients with urinary tract infections (UTIs).
      METHODS: Observational, retro-prospective analytical study of adult patients
      (>=15 years) diagnosed with UTI in an emergency department from August 2012 to
      January 2013. RESULTS: The study included 328 patients diagnosed with UTI, with a
      mean age of 52+/-22 years, 74% of whom were women. Of these, 43 (13.1%) had
      bacteremia. For predicting bacteremia, PCT achieved the largest area under the
      receiver operating characteristic curve (ROC-AUC) at .993 (95% CI .987-1;
      P<.001). A cutoff>=1.16ng/mL achieves a sensitivity of 100%, a specificity of
      97%, a positive predictive value of 84% and a negative predictive value of 100%.
      Lactate achieved an ROC-AUC of .844, and CRP achieved only .534. The mean values
      when comparing PCT levels in patients with UTIs with and without bacteremia were
      8.08+/-16.37 and .34+/-.37ng/mL, respectively (P<.001). CONCLUSIONS: For patients
      with UTIs in the emergency department, PCT achieves considerable diagnostic
      performance for suspecting bacteremia, a performance greater than that of
      lactate, CRP and leukocytes.

PMID- 25944773
TI  - How you get there from here: interaction of visual landmarks and path integration
      in human navigation.
AB  - How do people combine their sense of direction with their use of visual landmarks
      during navigation? Cue-integration theory predicts that such cues will be
      optimally integrated to reduce variability, whereas cue-competition theory
      predicts that one cue will dominate the response direction. We tested these
      theories by measuring both accuracy and variability in a homing task while
      manipulating information about path integration and visual landmarks. We found
      that the two cues were near-optimally integrated to reduce variability, even when
      landmarks were shifted up to 90 degrees . Yet the homing direction was dominated
      by a single cue, which switched from landmarks to path integration when landmark
      shifts were greater than 90 degrees . These findings suggest that cue integration
      and cue competition govern different aspects of the homing response: Cues are
      integrated to reduce response variability but compete to determine the response
      direction. The results are remarkably similar to data on animal navigation, which
      implies that visual landmarks reset the orientation, but not the precision, of
      the path-integration system. 

PMID- 25944774
TI  - Publication Bias and the Validity of Evidence: What's the Connection?

PMID- 25944775
TI  - The connection is in the data: we should consider them all.

PMID- 25944776
TI  - Suture-Free Ureterovesical Anastomosis Using a Microvascular Anastomosis System:
      Canine Cadaveric Study.
AB  - OBJECTIVE: To describe a suture-free ureterovesical anastomosis using a
      microvascular anastomotic system (MAS) and compare the surgical time and bursting
      pressure to a sutured ureterovesical anastomosis (SA) with and without an
      extravesical seromuscular tunnel (EVSMT). STUDY DESIGN: Randomized, unblocked
      design, ex vivo study. ANIMALS: Three canine cadavers. METHODS: For each cadaver,
      the ureters were sectioned into 3 equal lengths. The 6 sections were randomly
      assigned to receive either the MAS or end-side SA. The first cadaver (3 MAS, 3
      SA) was used to refine the technique, and the remaining 2 cadavers were used for
      evaluation. Surgical time and bursting pressure of the anastomosis were compared
      between MAS and SA (n = 6 per technique). After bursting pressure testing of each
      anastomosis, an SMT was created over the anastomoses. Bursting pressures were
      again recorded and compared across techniques. RESULTS: The surgery time was
      significantly shorter for MAS (median 5.4 minutes) than SA (median 15.8 minutes;
      P = .002). The bursting pressure was significantly higher for MAS (median 189.5
      cmH2 O) than SA (median 64 cmH2 O; P = .002). The bursting pressure for MAS-EVSMT
      (median 398.5 cmH2 O) was not significantly different from the SA-EVSMT (median
      321 cmH2 O, P = .567); however, the creation of an SMT significantly increased
      the bursting pressure for both techniques (P = .028, respectively). CONCLUSION:
      This study demonstrated the feasibility of a suture-free ureterovesical
      anastomosis in the canine cadaver using a commercially available MAS. The MAS
      anastomosis was faster and resulted in higher bursting pressures than SA. The
      creation of an SMT improved the bursting resistance of both techniques but there
      was no difference between the techniques covered by an EVSMT.

PMID- 25944777
TI  - Pulmonary Hypertension in the Intensive Care Unit.
AB  - Pulmonary hypertension occurs as the result of disease processes increasing
      pressure within the pulmonary circulation, eventually leading to right
      ventricular failure. Patients may become critically ill from complications of
      pulmonary hypertension and right ventricular failure or may develop pulmonary
      hypertension as the result of critical illness. Diagnostic testing should
      evaluate for common causes such as left heart failure, hypoxemic lung disease and
      pulmonary embolism. Relatively few patients with pulmonary hypertension
      encountered in clinical practice require specific pharmacologic treatment of
      pulmonary hypertension targeting the pulmonary vasculature. Management of right
      ventricular failure involves optimization of preload, maintenance of systemic
      blood pressure and augmentation of inotropy to restore systemic perfusion.
      Selected patients may require pharmacologic therapy to reduce right ventricular
      afterload by directly targeting the pulmonary vasculature, but only after
      excluding elevated left heart filling pressures and confirming increased
      pulmonary vascular resistance. Critically-ill patients with pulmonary
      hypertension remain at high risk of adverse outcomes, requiring a diligent and
      thoughtful approach to diagnosis and treatment. 

PMID- 25944778
TI  - Editorial overview: Cytokines: New roles for old friends!

PMID- 25944780
TI  - Technical guide for applications of gene expression profiling in human health
      risk assessment of environmental chemicals.
AB  - Toxicogenomics promises to be an important part of future human health risk
      assessment of environmental chemicals. The application of gene expression
      profiles (e.g., for hazard identification, chemical prioritization, chemical
      grouping, mode of action discovery, and quantitative analysis of response) is
      growing in the literature, but their use in formal risk assessment by regulatory
      agencies is relatively infrequent. Although additional validations for specific
      applications are required, gene expression data can be of immediate use for
      increasing confidence in chemical evaluations. We believe that a primary reason
      for the current lack of integration is the limited practical guidance available
      for risk assessment specialists with limited experience in genomics. The present
      manuscript provides basic information on gene expression profiling, along with
      guidance on evaluating the quality of genomic experiments and data, and
      interpretation of results presented in the form of heat maps, pathway analyses
      and other common approaches. Moreover, potential ways to integrate information
      from gene expression experiments into current risk assessment are presented using
      published studies as examples. The primary objective of this work is to
      facilitate integration of gene expression data into human health risk assessments
      of environmental chemicals. 

PMID- 25944779
TI  - Daily exposure to summer temperatures affects the motile subpopulation structure
      of epididymal sperm cells but not male fertility in an in vivo rabbit model.
AB  - High temperatures have negative effects on sperm quality leading to temporary or
      permanent sterility. The aim of the study was to assess the effect of long
      exposure to summer circadian heat stress cycles on sperm parameters and the
      motile subpopulation structure of epididymal sperm cells from rabbit bucks.
      Twelve White New Zealand rabbit bucks were exposed to a daily constant
      temperature of the thermoneutral zone (from 18  degrees C to 22  degrees C;
      control group) or exposed to a summer circadian heat stress cycles (30  degrees
      C, 3 h/day; heat stress group). Spermatozoa were flushed from the epididymis and
      assessed for sperm quality parameters at recovery. Sperm total motility and
      progressivity were negatively affected by high temperatures (P < 0.05), as were
      also specific motility parameters (curvilinear velocity, linear velocity, mean
      velocity, straightness coefficient, linearity coefficient, wobble coefficient,
      and frequency of head displacement; P < 0.05, but not the mean amplitude of
      lateral head displacement). Heat stress significantly increased the percentage of
      less-motile sperm subpopulations, although the percentage of the high-motile
      subpopulation was maintained, which is consistent with the fact that no effect
      was detected on fertility rates. However, prolificacy was reduced in females
      submitted to heat stress when inseminated by control bucks. In conclusion, our
      results suggest that environmental high temperatures are linked to changes in the
      proportion of motile sperm subpopulations of the epididymis, although fertility
      is still preserved despite the detrimental effects of heat stress. On the other
      hand, prolificacy seems to be affected by the negative effects of high
      temperatures, especially by altering female reproduction.

PMID- 25944782
TI  - SSR characterization of Oryza glumaepatula populations from the Brazilian Amazon
      and Cerrado biomes.
AB  - The level and distribution of the genetic variability in 18 natural populations
      of Oryza glumaepatula that were collected from two Brazilian states were
      estimated using a set of 23 highly informative SSR markers. Samples comprising 78
      and 117 individuals from populations of the states of Tocantins and Roraima,
      respectively, were evaluated in order to integrate and support previous studies
      that were carried out with populations of O. glumaepatula from Brazil. A total of
      189 alleles were identified with an average of 8.22 alleles per locus. The 11
      populations from Roraima presented, in combination, a higher genetic diversity
      (HE = 0.245) compared with that of the seven populations from Tocantins (HE =
      0.212). All of the populations showed high and significant inbreeding values
      (mean f = 0.59); however, the mean was higher in Tocantins populations,
      indicating a higher gene flow in Roraima populations. The overall coefficient of
      genetic differentiation (FST) among the populations was high and significant
      (0.59) and was higher in Tocantins due to the isolation of each population, in
      contrast to Roraima, where gene flow occurred more frequently. The SSR panel used
      in this work resulted to be informative (polymorphism information content =
      0.201) for assessing genetic structure in O. glumaepatula populations. 

PMID- 25944781
TI  - Cross talk between cytokine and hyperthermia-induced pathways: identification of
      different subsets of NF-kappaB-dependent genes regulated by TNFalpha and heat
      shock.
AB  - Heat shock inhibits NF-kappaB signaling, yet the knowledge about its influence on
      the regulation of NF-kappaB-dependent genes is limited. Using genomic approaches,
      i.e., expression microarrays and ChIP-Seq, we aimed to establish a global picture
      for heat shock-mediated impact on the expression of genes regulated by TNFalpha
      cytokine. We found that 193 genes changed expression in human U-2 osteosarcoma
      cells stimulated with cytokine (including 77 genes with the kappaB motif in the
      proximal promoters). A large overlap between sets of genes modulated by cytokine
      or by heat shock was revealed (86 genes were similarly affected by both stimuli).
      Binding sites for heat shock-induced HSF1 were detected in regulatory regions of
      1/3 of these genes. Furthermore, pre-treatment with heat shock affected the
      expression of 2/3 of cytokine-modulated genes. In the largest subset of co
      affected genes, heat shock suppressed the cytokine-mediated activation
      (antagonistic effect, 83 genes), which genes were associated with the canonical
      functions of NF-kappaB signaling. However, subsets of co-activated and co
      repressed genes were also revealed. Importantly, pre-treatment with heat shock
      resulted in the suppression of NF-kappaB binding in the promoters of the cytokine
      upregulated genes, either antagonized or co-activated by both stimuli. In
      conclusion, we confirmed that heat shock inhibited activation of genes involved
      in the classical cytokine-mediated functions of NF-kappaB. On the other hand,
      genes involved in transcription regulation were over-represented in the subset of
      genes upregulated by both stimuli. This suggests the replacement of NF-kappaB
      mediated regulation by heat shock-mediated regulation in the latter subset of
      genes, which may contribute to the robust response of cells to both stress
      conditions. 

PMID- 25944783
TI  - Rapid and accurate identification of Streptococcus equi subspecies by MALDI-TOF
      MS.
AB  - Streptococcus equi includes very important animal and human pathogens. S. equi
      subsp. equi (SEE) is a highly pathogenic equine specific subspecies, while S.
      equi subsp. zooepidemicus (SEZ) and S. equi subsp. ruminatorum are opportunistic
      pathogens of various animal species and humans. Due to great phenotypic and
      sequence similarity between three subspecies their discrimination remains
      difficult. In this study, we aimed to design and validate a novel, Superspectra
      based, MALDI-TOF MS approach for reliable, rapid and cost-effective
      identification of SEE and SEZ, the most frequent S. equi subspecies in horses.
      Superspectra created in this study enabled correct identification of 86 strains
      belonging to different subspecies of S. equi, isolated from various hosts,
      infection sites and years. In general, higher average identification accuracy was
      achieved for SEE (99.0+/-3.0%) than for SEZ (93.3+/-7.5%). This result may be
      attributed to the highly clonal population structure of SEE, as opposed to the
      diversity of SEZ seen in horses. Importantly strains with atypical colony
      appearance both within SEE and SEZ did not affect correct identification of the
      strains by MALDI-TOF MS. Atypical colony variants are often associated with a
      higher persistence or virulence of S. equi, thus their correct identification
      using the current method strengthens its potential use in routine clinical
      diagnostics. In conclusion, reliable identification of S. equi subspecies was
      achieved by combining a MALDI-TOF MS method with spectra analyses using the
      SARAMIS database. Additionally, first results on subtyping of SEZ indicated that
      a more refined discrimination, for example for epidemiological surveys, may be
      possible.

PMID- 25944784
TI  - Response to: "Comments on: "A polyphasic approach leading to the revision of the
      genus Planktothrix (Cyanobacteria) and its type species, P. agardhii, and
      proposal for integrating the emended valid botanical taxa, as well as three new
      species, Planktothrix paucivesiculata sp. nov.(ICNP), Planktothrix tepida sp.
      nov.(ICNP), and Planktothrix serta sp. nov.(ICNP), as genus and species names
      with nomenclature standing under the ICNP," by V. Gaget, M. Welker, R. Rippka,
      and N. Tandeau de Marsac, Syst. Appl. Microbiol. (2015),
      http://dx.doi.org/10.1016/j.syapm.2015.02.004", by A. Oren [Syst. Appl.
      Microbiol. (2015), doi:10.1016/j.syapm.2015.03.002].

PMID- 25944785
TI  - Protocatechuic acid activates key components of insulin signaling pathway
      mimicking insulin activity.
AB  - SCOPE: Insulin resistance represents an independent risk factor for metabolic and
      cardiovascular diseases. Researchers have been interested in identifying active
      harmless compounds, as many insulin-sensitizing drugs have shown unwanted side
      effects. It has been demonstrated that anthocyanins and one of their
      representative metabolites, protocatechuic acid (PCA), ameliorate hyperglycemia,
      and insulin sensitivity. This study investigated the mechanism of action of PCA
      responsible for the glucose uptake upregulation. METHODS AND RESULTS: In human
      visceral adipocytes, PCA stimulated insulin receptor substrate-1 (IRS-1) tyrosine
      phosphorylation (+40% with respect to untreated cells) and the downstream events,
      i.e. phosphoinositide 3-kinase binding to IRS-1 and Akt phosphorylation (+100%,
      +180%, respectively, with respect to untreated cells). The insulin-like activity
      of PCA seemed to be mediated by insulin receptor since by inhibiting its
      autophosphorylation, the PCA effects were completely abolished. Furthermore, PCA
      was able to activate adenosine monophosphate-activated protein kinase, a
      serine/threonine kinase whose activation elicits insulin-sensitizing effects.
      CONCLUSION: This study showed that PCA stimulates the insulin signaling pathway
      in human adipocytes increasing GLUT4 translocation and glucose uptake. Decreasing
      insulin resistance is a most desirable aim to be reached for an effective
      therapeutic/preventive action against metabolic syndrome and type 2 diabetes.
      Identifying specific food/food components able to improve glucose metabolism can
      offer an attractive, novel, and economical strategy.

PMID- 25944786
TI  - [Poisonous snakebites: A five-year experience].

PMID- 25944787
TI  - A familial 7q36.3 duplication associated with agenesis of the corpus callosum.
AB  - Small chromosomal duplications involving 7q36.3 have rarely been reported. This
      clinical report describes four individuals from a three-generation family with
      agenesis of the corpus callosum (ACC) and a 0.73 Mb duplication of 7q36.3
      detected by array CGH. The 7q36.3 duplication involves two genes: RNA Binding
      Motif Protein 33 (RBM33) and Sonic Hedgehog (SHH). Most affected family members
      had mild intellectual disability or borderline intellectual functioning,
      macrocephaly, a broad forehead, and widely spaced eyes. Two individuals had a
      Chiari type I malformation. This is the first family reported with ACC associated
      with a small duplication of these genes. While we cannot establish causation for
      the relationship between any single gene and the ACC in this family, there is a
      role for SHH in the formation of the corpus callosum through correct patterning
      and assembly of the commissural plate, and these data concur with vertebrate
      studies showing that a gain of SHH expands the facial primordium.

PMID- 25944788
TI  - Clinical experiences of ultrasound-guided transversus thoracic muscle plane
      block: a clinical experience.

PMID- 25944789
TI  - Caffeine Improves Heart Rate Without Improving Sepsis Survival.
AB  - INTRODUCTION: Caffeine is consumed on a daily basis for its nervous system
      stimulant properties and is a global adenosine receptor antagonist. Because
      adenosine receptors have been found to play a major role in regulating the immune
      response to a septic insult, we investigated if caffeine consumption prior to a
      septic insult would alter immunological and physiological responses, as well as
      survival. METHODS: Two separate experimental designs were used, both using
      outbred female ICR mice. In the first experiment, mice were administered 20 mg/kg
      of caffeine (equal to 2-3 cups of coffee for a human) or normal saline
      intraperitoneally at the time of cecal ligation and puncture (CLP). Immunological
      parameters including cytokines and local cell recruitment were measured. In the
      second experiment, caffeine (10 mg/kg per hour) was delivered continuously for 24
      h via a subcutaneous infusion pump placed the day prior to CLP, and hemodynamic
      parameters were examined. In both experiments, survival was followed for 5 days.
      RESULTS: A single dose of caffeine at the initiation of sepsis did not alter
      survival. This single dose of caffeine did significantly increase in plasma
      levels of the chemokine KC 6 h after the onset of sepsis compared with septic
      mice given normal saline. There were no changes in interleukin 6 (IL-6) or IL-10
      levels in the caffeine groups. Peritoneal lavages performed 24 h after CLP showed
      no difference in the levels of IL-6, tumor necrosis factor, KC, macrophage
      inflammatory protein 1, IL-10, or the IL-1 receptor antagonist between caffeine-
      and normal saline-treated mice. In addition, the lavages yielded similar numbers
      of cells (4.1 * 10 vehicle vs. 6.9 * 10 caffeine) and bacterial colony-forming
      units (CFUs, 4.1 million CFUs vehicle vs. 2.8 million CFUs caffeine). In the
      infusion group, caffeine also did not alter survival. However, caffeine infusion
      did increase the heart rate prior to CLP and prevented the decline in heart rate
      after CLP. CONCLUSION: Caffeine increased the heart rate in mice but does not
      impact cytokine responses or survival during the acute phase of a polymicrobial
      sepsis challenge. These data indicate that patients consuming caffeine will not
      be at risk for increased sepsis mortality.

PMID- 25944790
TI  - alpha-Enolase Causes Proinflammatory Activation of Pulmonary Microvascular
      Endothelial Cells and Primes Neutrophils Through Plasmin Activation of Protease
      Activated Receptor 2.
AB  - Proinflammatory activation of vascular endothelium leading to increased surface
      expression of adhesion molecules and neutrophil (PMN) sequestration and
      subsequent activation is paramount in the development of acute lung injury and
      organ injury in injured patients. We hypothesize that alpha-enolase, which
      accumulates in injured patients, primes PMNs and causes proinflammatory
      activation of endothelial cells leading to PMN-mediated cytotoxicity. METHODS:
      Proteomic analyses of field plasma samples from injured versus healthy patients
      were used for protein identification. Human pulmonary microvascular endothelial
      cells (HMVECs) were incubated with alpha-enolase or thrombin, and intercellular
      adhesion molecule-1 surface expression was measured by flow cytometry. A two
      event in vitro model of PMN cytotoxicity HMVECs activated with alpha-enolase,
      thrombin, or buffer was used as targets for lysophosphatidylcholine-primed or
      buffer-treated PMNs. The PMN priming activity of alpha-enolase was completed, and
      lysates from both PMNs and HMVECs were immunoblotted for protease-activated
      receptor 1 (PAR-1) and PAR-2 and coprecipitation of alpha-enolase with PAR-2 and
      plasminogen/plasmin. RESULTS: alpha-Enolase increased 10.8-fold in injured
      patients (P < 0.05). Thrombin and alpha-enolase significantly increased
      intercellular adhesion molecule-1 surface expression on HMVECs, which was
      inhibited by antiproteases, induced PMN adherence, and served as the first event
      in the two-event model of PMN cytotoxicity. alpha-Enolase coprecipitated with PAR
      2 and plasminogen/plasmin on HMVECs and PMNs and induced PMN priming, which was
      inhibited by tranexamic acid, and enzymatic activity was not required.
      CONCLUSIONS: alpha-Enolase increases after injury and may activate pulmonary
      endothelial cells and prime PMNs through plasmin activity and PAR-2 activation.
      Such proinflammatory endothelial activation may predispose to PMN-mediated organ
      injury.

PMID- 25944791
TI  - Prolonged Endoplasmic Reticulum-Stressed Hepatocytes Drive an Alternative
      Macrophage Polarization.
AB  - Relatively little is known about the effects of hepatocytes on hepatic
      macrophages, particularly under the situation of endoplasmic reticulum (ER)
      stress. We examined the effects of hepatocytes conditioned media (CM) from HepG2
      treated with ER stress inducers, tunicamycin or thapsigargin, on the secretion of
      cytokines, expression of ER stress markers, and polarization of phorbol myristate
      acetate-activated THP-1 cells (pTHP-1). We found that CM decreased the production
      of the proinflammatory cytokines including tumor necrosis factor alpha,
      interleukin 6 (IL-6), and IL-1beta as well as other cytokines and chemokines from
      pTHP-1 cells. These effects are mediated by the inhibition of TLR4 expression and
      nuclear factor kappaB signaling pathway. In addition, hepatocytes CM increased
      the expression of binding immunoglobulin protein and the transcription factor
      C/EBP homologous protein (CHOP) in pTHP-1 cells. Preconditioning with ER stress
      inhibitor, small molecular chaperone 4-phenylbutyrate before addition of ER
      stressors, attenuated the ER stress in macrophages, the property of hepatocytes
      CM to alter tumor necrosis factor alpha production and nuclear factor kappaB
      expression by macrophages. Remarkably, treatment of macrophage with these CM
      leads to an alternative activation of macrophages mediated by peroxisome
      proliferator-activated receptor gamma signaling pathway, which might be resulted
      from the secretion of IL-10 and IL-4 as well as releasing apoptotic bodies from
      hepatocytes under ER stress. Our results highlight a mechanism of ER stress
      transmission from hepatocytes to macrophage that drives an alternative activation
      of macrophages, which depends on the exposure of hepatocytes to severe and
      prolonged ER stress. 

PMID- 25944793
TI  - Oxidative Stress Increases Surface Toll-Like Receptor 4 Expression in Murine
      Macrophages Via Ceramide Generation.
AB  - Multiorgan failure is a major cause of late mortality following trauma. Oxidative
      stress generated during shock/resuscitation contributes to tissue injury by
      priming the immune system for an exaggerated response to subsequent inflammatory
      stimuli, such as lipopolysaccharide (LPS). We recently reported that oxidative
      stress causes rapid recruitment of the LPS receptor Toll-like receptor 4 (TLR4)
      to membrane lipid rafts, thus increasing LPS responsiveness and cellular priming.
      We hypothesized that activation of Src family kinases by oxidants might
      contribute to these events. We utilized microscopy, flow cytometry, Western
      blotting, and thin-layer chromatography methods. Using hydrogen peroxide in vitro
      and hemorrhagic shock/resuscitation in vivo, oxidant-induced TLR4 translocation
      in macrophages occurred in an Src-dependent manner. Approaches supporting this
      conclusion included pharmacologic inhibition of the Src family kinases by PP2,
      Src inhibition by a molecular approach of cell transfection with Csk, and genetic
      inhibition of all Src kinases relevant to the monocyte/macrophage lineage in
      hckfgrlyn triple knockout mice. To evaluate the upstream molecules involved in
      Src activation, we evaluated the ability of oxidative stress to activate the
      bioactive lipid molecule ceramide. Oxidants induced ceramide generation in
      macrophages both in vitro and in vivo, an effect that appears to be due to
      activation of the acid sphingomyelinase. Using pharmacological approaches,
      ceramide was shown to be both necessary and sufficient to mediate TLR4
      translocation to the plasma membrane in an Src-dependent manner. This study
      identifies a hierarchy of signaling molecules following oxidative stress that
      might represent novel targets for therapy in critical illness and organ injury. 

PMID- 25944792
TI  - Comparison of the Proinflammatory and Procoagulant Properties of Nuclear,
      Mitochondrial, and Bacterial DNA.
AB  - PURPOSE: Cell-free DNA (CFDNA) is elevated in sepsis and correlates with
      mortality. This DNA may come from nuclear, mitochondrial, or bacterial sources.
      Cell-free DNA from all three sources may play a pathogenic role in sepsis via
      activation of coagulation through the contact pathway, whereas CpG motifs on
      bacterial and mitochondrial DNA may additionally stimulate inflammatory responses
      via Toll-like receptor 9. This study elucidates the relative effects of nuclear,
      mitochondrial, and bacterial DNA on inflammatory and procoagulant pathways with
      relevance to sepsis. METHODS: DNA was extracted from plasma of septic patients
      and control subjects, and nuclear and mitochondrial CFDNA concentrations were
      measured by quantitative polymerase chain reaction. Viability of primary cultured
      human neutrophils was measured by flow cytometry for phosphatidyl serine exposure
      and cell permeability to propidium iodide. Continuous thrombin generation was
      measured with a fluorogenic substrate (Technothrombin, Vienna, Austria).
      Interleukin 6 secretion was measured by enzyme-linked immunosorbent assay.
      Platelet activation was measured by flow cytometry for P-selectin and activated
      alphaIIbbeta3. RESULTS: Mitochondrial DNA and nuclear DNA were elevated in plasma
      from septic patients compared with control subjects. Both mitochondrial and
      bacterial DNA prolonged neutrophil viability. Bacterial DNA increased neutrophil
      interleukin 6 secretion, but mitochondrial and nuclear DNA did not. Nuclear,
      mitochondrial, and bacterial DNA increased thrombin generation in platelet-poor
      plasma to a similar degree in a FXI- and FXII-dependent manner, indicating
      dependence on the intrinsic pathway of coagulation. Independently of coagulation,
      DNA from all three sources was capable of causing activation of platelet integrin
      alphaIIbbeta3. CONCLUSIONS: Cell-free DNA from nuclear, mitochondrial, and
      bacterial sources have varying proinflammatory effects, although all three have
      similar procoagulant and platelet-stimulating potential. The pathophysiological
      effects of CFDNA in sepsis may vary with the source of DNA.

PMID- 25944794
TI  - FTY720 Attenuates Acute Pancreatitis in Hypertriglyceridemic Apolipoprotein CIII
      Transgenic Mice.
AB  - Hypertriglyceridemic pancreatitis (HTGP) is often encountered clinically as a
      common form of recurrent acute pancreatitis (AP). It is important to evaluate the
      management of severe hypertriglyceridemia (HTG) or anti-inflammation in the
      prophylaxis of HTGP in the clinic. FTY720 (2-amino-2[2-(4-octylphenyl) ethyl]-1,
      3-propanediol) is a new anti-inflammatory agent with low toxicity and reported to
      ameliorate lung injury with pancreatitis in rat. We evaluated its protective
      affection on AP induced by seven hourly intraperitoneal injection of cerulein in
      apolipoprotein CIII transgenic mice with severe HTG. FTY720 at 1.5 mg/kg was
      administered by gastric lavage daily for 3 days before induction of AP. The
      effects of FTY720 to protect against HTGP were assessed by serum amylase,
      pancreatic pathological scores, immunostaining, and the expression of
      inflammatory cytokine genes. As a result, injection of cerulein resulted in more
      severe pathological changes of AP and higher monocyte chemoattractant protein 1
      expression in the pancreas in transgenic than in nontransgenic mice. FTY720
      pretreatment improved the pathological severity of AP and decreased the
      expression of monocyte chemoattractant protein 1 in the pancreas significantly,
      especially near fourfold reduction in transgenic mice. However, FTY720 did not
      affect plasma triglyceride levels, and other inflammatory factors and plasma
      amylase were not correlated with the extent of pancreatic damage in AP with or
      without FTY720 administration. In summary, our study in a new model,
      apolipoprotein CIII transgenic mice, demonstrated that HTG mice are susceptible
      to induction of AP. Prophylactic treatment of FTY720 can significantly attenuate
      cerulein-induced AP and hence warrant further investigation of sphingosine-1
      phosphate receptors agonist for potential clinical application in recurrent
      attacks of HTGP. 

PMID- 25944795
TI  - What's science? Where's science? Science journalism in German print media.
AB  - This article examines the current state of science coverage in German print
      media. It deals with the following questions: (1) how the main characteristics of
      science journalism can be described, (2) whether there is a difference between
      various scientific fields, and (3) how different definitions of science
      journalism lead to differing findings. Two forms of science coverage were
      analyzed in a standardized, two-part content analysis of German newspapers (N =
      1730 and N = 1640). The results show a significant difference between a narrow
      and a broad definition of science journalism. In the classic understanding,
      science journalism is prompted by scientific events and is rather noncritical.
      Science coverage in a broad sense is defined by a wider range of journalistic
      styles, driven by non-scientific events, and with a focus on the statements of
      scientific experts. Furthermore, the study describes the specific role of the
      humanities and social sciences in German science coverage.

PMID- 25944797
TI  - National and Gender Measurement Invariance of the Utrecht-Management of Identity
      Commitments Scale (U-MICS): A 10-Nation Study With University Students.
AB  - The purpose of this study was to examine the psychometric properties of the
      Utrecht-Management of Identity Commitments Scale (U-MICS), a self-report measure
      aimed at assessing identity processes of commitment, in-depth exploration, and
      reconsideration of commitment. We tested its factor structure in university
      students from a large array of cultural contexts, including 10 nations located in
      Europe (i.e., Italy, the Netherlands, Poland, Portugal, Romania, and
      Switzerland), Middle East (i.e., Turkey), and Asia (i.e., China, Japan, and
      Taiwan). Furthermore, we tested national and gender measurement invariance.
      Participants were 6,118 (63.2% females) university students aged from 18 to 25
      years (Mage = 20.91 years). Results indicated that the three-factor structure of
      the U-MICS fitted well in the total sample, in each national group, and in gender
      groups. Furthermore, national and gender measurement invariance were established.
      Thus, the U-MICS can be fruitfully applied to study identity in university
      students from various Western and non-Western contexts. 

PMID- 25944796
TI  - A phase II clinical study of using nab-paclitaxel as second-line chemotherapy for
      Chinese patients with advanced non-small cell lung cancer.
AB  - The aim of this clinical study was to evaluate the efficacy and safety of nab
      paclitaxel to treat patients with advanced non-small cell lung cancer (NSCLC) who
      failed first-line chemotherapy. Eligible patients had advanced NSCLC and had been
      treated with first-line platinum-based chemotherapy but still had disease
      progression. Patients received nab-paclitaxel 100 mg/m(2) (i.v.) on days 1, 8 and
      15 of a 28-day cycle. Primary endpoint is 6-month progression-free survival
      (PFS). Fifty-six patients with advanced NSCLC were enrolled in the study (55.4 %
      male patients, 44.6 % female patients; median age 59.6 years; ranging from 32 to
      83 years). Six-month PFS rate was 18 % (95 % CI 7.8-28.7 %). Median PFS was 3.5
      months (95 % CI 1.9-5.8 months). Median overall survival was 6.8 months (95 % CI
      4.7-9.3 months). No complete responses were achieved. Overall response rate was
      16.1 % (95 % CI 8.9-24.7 %). Grade 3 or 4 adverse events (AEs) were observed in
      patients receiving nab-paclitaxel. The most common grade 3 or 4 AEs were
      dizziness, pulmonary embolism and fatigue. Nab-paclitaxel showed clinically
      equivalent efficacy on patients' survivals and response rates, as compared with
      other FDA-approved second-line chemotherapy agents. Given the tolerability on
      grade 3 or 4 adverse events, nab-paclitaxel may be considered an alternative
      second-line treatment option for NSCLC.

PMID- 25944798
TI  - Interpretive Reliability of Six Computer-Based Test Interpretation Programs for
      the Minnesota Multiphasic Personality Inventory-2.
AB  - The reliability of six Minnesota Multiphasic Personality Inventory-Second edition
      (MMPI-2) computer-based test interpretation (CBTI) programs was evaluated across
      a set of 20 commonly appearing MMPI-2 profile codetypes in clinical settings.
      Evaluation of CBTI reliability comprised examination of (a) interrater
      reliability, the degree to which raters arrive at similar inferences based on the
      same CBTI profile and (b) interprogram reliability, the level of agreement across
      different CBTI systems. Profile inferences drawn by four raters were
      operationalized using q-sort methodology. Results revealed no significant
      differences overall with regard to interrater and interprogram reliability. Some
      specific CBTI/profile combinations (e.g., the CBTI by Automated Assessment
      Associates on a within normal limits profile) and specific profiles (e.g., the
      4/9 profile displayed greater interprogram reliability than the 2/4 profile) were
      interpreted with variable consensus (alpha range = .21-.95). In practice, users
      should consider that certain MMPI-2 profiles are interpreted more or less
      consensually and that some CBTIs show variable reliability depending on the
      profile. 

PMID- 25944799
TI  - Negative psychosocial and heavy physical workloads associated with
      musculoskeletal pain interfering with normal life in older adults: cross
      sectional analysis.
AB  - AIMS: Pain is one of the most frequent reasons for seeking health care, and is
      thus a public health problem. Although there is a progressive increase in pain
      and impaired physical function with age, few studies are performed on older
      adults. The aim of this study was to investigate if there are associations
      between musculoskeletal pain interfering with normal life in older adults and
      physical and psychosocial workloads through life. METHODS: The association of
      heavy physical workload and negative psychosocial workload and musculoskeletal
      pain interfering with normal life (SF 12) was analyzed by multiple logistic
      regression. The model was adjusted for eight background covariates: age, gender,
      growing-up environment, educational level, if living alone or not, obesity,
      smoking, and leisure physical activity. RESULTS: Negative psychosocial and heavy
      physical workloads were independently associated with musculoskeletal pain
      interfering with normal life (adjusted OR: 4.44, 95% CI: 2.84-6.92), and
      (adjusted OR: 1.88, 95% CI: 1.20-2.93), respectively. The background covariates
      female gender and higher education were also associated with musculoskeletal pain
      interfering with normal life, and physical leisure activity was inversely
      associated. CONCLUSIONS: The findings suggest that negative psychosocial and
      heavy physical workloads are strongly associated with musculoskeletal pain
      interfering with normal life in older adults.

PMID- 25944800
TI  - Differential Expression of Immune-Regulatory Genes Associated with PD-L1 Display
      in Melanoma: Implications for PD-1 Pathway Blockade.
AB  - PURPOSE: Blocking the immunosuppressive PD-1/PD-L1 pathway has antitumor activity
      in multiple cancer types, and PD-L1 expression on tumor cells and infiltrating
      myeloid cells correlates with the likelihood of response. We previously found
      that IFNG (interferon-gamma) was overexpressed by tumor-infiltrating lymphocytes
      in PD-L1(+) versus PD-L1(-) melanomas, creating adaptive immune resistance by
      promoting PD-L1 display. This study was undertaken to identify additional factors
      in the PD-L1(+) melanoma microenvironment coordinately contributing to
      immunosuppression. EXPERIMENTAL DESIGN: Archived, formalin-fixed paraffin
      embedded melanoma specimens were assessed for PD-L1 protein expression at the
      tumor cell surface with IHC. Whole-genome expression analysis, quantitative (q)RT
      PCR, IHC, and functional in vitro validation studies were used to assess factors
      differentially expressed in PD-L1(+) versus PD-L1(-) melanomas. RESULTS:
      Functional annotation clustering based on whole-genome expression profiling
      revealed pathways upregulated in PD-L1(+) melanomas, involving immune cell
      activation, inflammation, and antigen processing and presentation. Analysis by
      qRT-PCR demonstrated overexpression of functionally related genes in PD-L1(+)
      melanomas, involved in CD8(+) T-cell activation (CD8A, IFNG, PRF1, and CCL5),
      antigen presentation (CD163, TLR3, CXCL1, and LYZ), and immunosuppression [PDCD1
      (PD-1), CD274 (PD-L1), and LAG3, IL10]. Functional studies demonstrated that some
      factors, including IL10 and IL32-gamma, induced PD-L1 expression on monocytes but
      not tumor cells. CONCLUSIONS: These studies elucidate the complexity of immune
      checkpoint regulation in the tumor microenvironment, identifying multiple factors
      likely contributing to coordinated immunosuppression. These factors may provide
      tumor escape mechanisms from anti-PD-1/PD-L1 therapy, and should be considered
      for cotargeting in combinatorial immunomodulation treatment strategies.

PMID- 25944801
TI  - Inhibition of Survivin with YM155 Induces Durable Tumor Response in Anaplastic
      Thyroid Cancer.
AB  - PURPOSE: Anaplastic thyroid cancer (ATC) is a rare but lethal malignancy without
      any effective therapy. The aim of this study is to use a high-throughput drug
      library screening to identify a novel therapeutic agent that targets dysregulated
      genes/pathways in ATC. EXPERIMENTALDESIGN: We performed quantitative high
      throughput screening (qHTS) in ATC cell lines using a compound library of 3,282
      drugs. Dysregulated genes in ATC were analyzed using genome-wide expression
      analysis and immunohistochemistry in human ATC tissue samples and ATC cell lines.
      In vitro and in vivo studies were performed for determining drug activity,
      effectiveness of targeting, and the mechanism of action. RESULTS: qHTS identified
      100 active compounds in three ATC cell lines. One of the most active agents was
      the first-in-class survivin inhibitor YM155. Genome-wide expression analysis and
      immunohistochemistry showed overexpression of survivin in human ATC tissue
      samples, and survivin was highly expressed in all ATC cell lines tested. YM155
      significantly inhibited ATC cellular proliferation. Mechanistically, YM155
      inhibited survivin expression in ATC cells. Furthermore, YM155 treatment reduced
      claspin expression, which was associated with S-phase arrest in ATC cells. In
      vivo, YM155 significantly inhibited growth and metastases and prolonged survival.
      CONCLUSIONS: Our data show that YM155 is a promising anticancer agent for ATC and
      that its target, survivin, is overexpressed in ATC. Our findings support the use
      of YM155 in clinical trials as a therapeutic option in advanced and metastatic
      ATC.

PMID- 25944802
TI  - First-in-Human Trial of a Novel Anti-Trop-2 Antibody-SN-38 Conjugate, Sacituzumab
      Govitecan, for the Treatment of Diverse Metastatic Solid Tumors.
AB  - PURPOSE: Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate (ADC)
      targeting Trop-2, a surface glycoprotein expressed on many epithelial tumors, for
      delivery of SN-38, the active metabolite of irinotecan. This phase I trial
      evaluated this ADC as a potential therapeutic for pretreated patients with a
      variety of metastatic solid cancers. EXPERIMENTAL DESIGN: Sacituzumab govitecan
      was administered on days 1 and 8 of 21-day cycles, with cycles repeated until
      dose-limiting toxicity or progression. Dose escalation followed a standard 3 + 3
      scheme with 4 planned dose levels and dose delay or reduction allowed. RESULTS:
      Twenty-five patients (52-60 years old, 3 median prior chemotherapy regimens) were
      treated at dose levels of 8 (n = 7), 10 (n = 6), 12 (n = 9), and 18 (n = 3)
      mg/kg. Neutropenia was dose limiting, with 12 mg/kg the maximum tolerated dose
      for cycle 1, but too toxic with repeated cycles. Lower doses were acceptable for
      extended treatment with no treatment-related grade 4 toxicities and grade 3
      toxicities limited to fatigue (n = 3), neutropenia (n = 2), diarrhea (n = 1), and
      leukopenia (n = 1). Using CT-based RECIST 1.1, two patients achieved partial
      responses (triple-negative breast cancer, colon cancer) and 16 others had stable
      disease as best response. Twelve patients maintained disease control with
      continued treatment for 16 to 36 weeks; 6 survived 15 to 20+ months. No
      preselection of patients based on tumor Trop-2 expression was done. CONCLUSIONS:
      Sacituzumab govitecan had acceptable toxicity and encouraging therapeutic
      activity in patients with difficult-to-treat cancers. The 8 and 10 mg/kg doses
      were selected for phase II studies.

PMID- 25944803
TI  - Creation of a Human Secretome: A Novel Composite Library of Human Secreted
      Proteins: Validation Using Ovarian Cancer Gene Expression Data and a Virtual
      Secretome Array.
AB  - PURPOSE: To generate a comprehensive "Secretome" of proteins potentially found in
      the blood and derive a virtual Affymetrix array. To validate the utility of this
      database for the discovery of novel serum-based biomarkers using ovarian cancer
      transcriptomic data. EXPERIMENTAL DESIGN: The secretome was constructed by
      aggregating the data from databases of known secreted proteins, transmembrane or
      membrane proteins, signal peptides, G-protein coupled receptors, or proteins
      existing in the extracellular region, and the virtual array was generated by
      mapping them to Affymetrix probeset identifiers. Whole-genome microarray data
      from ovarian cancer, normal ovarian surface epithelium, and fallopian tube
      epithelium were used to identify transcripts upregulated in ovarian cancer.
      RESULTS: We established the secretome from eight public databases and a virtual
      array consisting of 16,521 Affymetrix U133 Plus 2.0 probesets. Using ovarian
      cancer transcriptomic data, we identified candidate blood-based biomarkers for
      ovarian cancer and performed bioinformatic validation by demonstrating
      rediscovery of known biomarkers including CA125 and HE4. Two novel top biomarkers
      (FGF18 and GPR172A) were validated in serum samples from an independent patient
      cohort. CONCLUSIONS: We present the secretome, comprising the most comprehensive
      resource available for protein products that are potentially found in the blood.
      The associated virtual array can be used to translate gene-expression data into
      cancer biomarker discovery. A list of blood-based biomarkers for ovarian cancer
      detection is reported and includes CA125 and HE4. FGF18 and GPR172A were
      identified and validated by ELISA as being differentially expressed in the serum
      of ovarian cancer patients compared with controls.

PMID- 25944804
TI  - Highly Expressed Genes in Rapidly Proliferating Tumor Cells as New Targets for
      Colorectal Cancer Treatment.
AB  - PURPOSE: The clinical management of colorectal cancer patients has significantly
      improved because of the identification of novel therapeutic targets such as EGFR
      and VEGF. Because rapid tumor proliferation is associated with poor patient
      prognosis, here we characterized the transcriptional signature of rapidly
      proliferating colorectal cancer cells in an attempt to identify novel candidate
      therapeutic targets. EXPERIMENTAL DESIGN: The doubling time of 52 colorectal
      cancer cell lines was determined and genome-wide expression profiling of a subset
      of these lines was assessed by microarray analysis. We then investigated the
      potential of genes highly expressed in cancer cells with faster growth as new
      therapeutic targets. RESULTS: Faster proliferation rates were associated with
      microsatellite instability and poorly differentiated histology. The expression of
      1,290 genes was significantly correlated with the growth rates of colorectal
      cancer cells. These included genes involved in cell cycle, RNA
      processing/splicing, and protein transport. Glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) and protoporphyrinogen oxidase (PPOX) were shown to have
      higher expression in faster growing cell lines and primary tumors. Pharmacologic
      or siRNA-based inhibition of GAPDH or PPOX reduced the growth of colon cancer
      cells in vitro. Moreover, using a mouse xenograft model, we show that treatment
      with the specific PPOX inhibitor acifluorfen significantly reduced the growth of
      three of the seven (42.8%) colon cancer lines investigated. CONCLUSIONS: We have
      characterized at the transcriptomic level the differences between colorectal
      cancer cells that vary in their growth rates, and identified novel candidate
      chemotherapeutic targets for the treatment of colorectal cancer.

PMID- 25944805
TI  - Sedimenticola thiotaurini sp. nov., a sulfur-oxidizing bacterium isolated from
      salt marsh sediments, and emended descriptions of the genus Sedimenticola and
      Sedimenticola selenatireducens.
AB  - A marine facultative anaerobe, strain SIP-G1T, was isolated from salt marsh
      sediments, Falmouth, MA, USA. Phylogenetic analysis of its 16S rRNA gene sequence
      indicated that it belongs to an unclassified clade of Gammaproteobacteria that
      includes numerous sulfur-oxidizing bacteria that are endosymbionts of marine
      invertebrates endemic to sulfidic habitats. Strain SIP-G1T is a member of the
      genus Sedimenticola, of which there is one previously described isolate,
      Sedimenticola selenatireducens AK4OH1T. S. selenatireducens AK4OH1T was obtained
      for further characterization and comparison with strain SIP-G1T. The two strains
      were capable of coupling the oxidation of thiosulfate, tetrathionate, elemental
      sulfur and sulfide to autotrophic growth and they produced sulfur inclusions as
      metabolic intermediates. They showed varying degrees of O2 sensitivity, but when
      provided amino acids or peptides as a source of energy, they appeared more
      tolerant of O2 and exhibited concomitant production of elemental sulfur
      inclusions. The organic substrate preferences and limitations of these two
      organisms suggest that they possess an oxygen-sensitive carbon fixation
      pathway(s). Organic acids may be used to produce NADPH through the TCA cycle and
      are used in the formation of polyhydroxyalkanoates. Cell-wall-deficient
      morphotypes appeared when organic compounds (especially acetate) were present in
      excess and reduced sulfur was absent. Levels of DNA-DNA hybridization (~47%) and
      phenotypic characterization indicate that strain SIP-G1T represents a separate
      species within the genus Sedimenticola, for which the name Sedimenticola
      thiotaurini sp. nov. is proposed. The type strain is SIP-G1T ( = ATCC BAA-2640T =
      DSM 28581T). The results also justify emended descriptions of the genus
      Sedimenticola and of S. selenatireducens.

PMID- 25944806
TI  - Palleronia soli sp. nov., isolated from a soil sample on reclaimed tidal land,
      and emended description of the genus Palleronia.
AB  - A Gram-stain-negative, strictly aerobic, non-motile, non-spore-forming, short rod
      shaped and moderately halophilic bacterial strain, CAU 1105T, was isolated from
      soil on reclaimed tidal land in Modo, Republic of Korea, and its taxonomic
      position was investigated using a polyphasic approach. Strain CAU 1105T grows
      optimally at a temperature of 37  degrees C at pH 7 in the presence of 3% (w/v)
      sea salt. Based on 16S rRNA gene sequence similarity analyses, the novel isolate
      was assigned to the genus Palleronia within the class Alphaproteobacteria and
      showed the highest 16S rRNA gene sequence similarity with Palleronia marisminoris
      B33T (95.4%). Strain CAU 1105T contained ubiquinone-10 as the only respiratory
      quinone and C18 : 1omega7c as the major cellular fatty acid. The DNA G+C content
      of strain CAU 1105T was 64.3 mol%. On the basis of phenotypic differentiation,
      phylogenetic and chemotaxonomic data, strain CAU 1105T represents a novel species
      of the genus Palleronia, for which the name Palleroniasoli sp. nov. is proposed.
      The type strain is CAU 1105T ( = KCTC 42298T = NBRC 110740T). An emended
      description of the genus Palleronia is also provided.

PMID- 25944807
TI  - Bacillus crescens sp. nov., isolated from soil.
AB  - Two bacterial strains (JC247T and JC248) were isolated from soil samples
      collected from Rann of Kutch, Gujarat, India. Colonies of both strains were
      creamy white. Cells were Gram-stain-positive, rods-to-curved rods (crescent
      shaped), and produced centrally located oval-shaped endospores. Major (>5 %)
      fatty acids of both strains were iso-C16  :  0, iso-C14  :  0, iso-C15  :  0, C16
      :  1omega11c and C16  :  0, with minor ( < 5 but >1 %) amounts of anteiso-C15  :
      0, anteiso-C17  :  0, iso-C16  :  1 H, iso-C17  :  0, iso-C18  :  0, C14  :  0,
      C17  :  0, C18  :  0, C18  :  1omega9c, iso-C17  :  1omega10c and anteiso-C17  : 
      0B/isoI. Diphosphatidylglycerol, phosphatidylethanolamine and
      phosphatidylglycerol were the major polar lipids of both strains. Cell-wall amino
      acids were l-alanine, d-alanine, d-glutamic acid and meso-diaminopimelic acid.
      The genomic DNA G+C content of strains JC247T and JC248 was 48.2 and 48.1 mol%,
      respectively. Both strains were closely related with mean DNA-DNA hybridization
      >90 %. 16S rRNA gene sequence analysis of both strains indicated that they are
      members of the genus Bacillus within the family Bacillaceae of the phylum
      Firmicutes. Both strains had a 16S rRNA gene sequence similarity of 96.93 % with
      Bacillus firmus NCIMB 9366T and < 96.92 % with other members of the genus
      Bacillus. Sequence similarity between strain JC247T and JC248 was 100 %. Distinct
      morphological, physiological and genotypic differences from previously described
      taxa support the classification of strains JC247T and JC248 as representatives of
      a novel species of the genus Bacillus, for which the name Bacilluscrescens sp.
      nov. is proposed. The type strain is JC247T ( = KCTC 33627T = LMG 28608T). 

PMID- 25944808
TI  - Sphingomonas zeae sp. nov., isolated from the stem of Zea mays.
AB  - A yellow-pigmented bacterial isolate (strain JM-791T) obtained from the healthy
      internal stem tissue of 1-month-old corn (Zea mays, cultivar 'Sweet Belle') grown
      at the Plant Breeding Unit of the E.V. Smith Research Center in Tallassee (Elmore
      county), Alabama, USA, was taxonomically characterized. The study employing a
      polyphasic approach, including 16S RNA gene sequence analysis, physiological
      characterization, estimation of the ubiquinone and polar lipid patterns, and
      fatty acid composition, revealed that strain JM-791T shared 16S rRNA gene
      sequence similarities with type strains of Sphingomonas paucimobilis (98.3%),
      Sphingomonas pseudosanguinis (97.5%) and Sphingomonas yabuuchiae (97.4%), but
      also showed pronounced differences, both genotypically and phenotypically. On the
      basis of these results, a novel species of the genus Sphingomonas is described,
      for which we propose the name Sphingomonas zeae sp. nov. with the type strain JM
      791T ( = LMG 28739T = CCM 8596T).

PMID- 25944809
TI  - Niveispirillum cyanobacteriorum sp. nov., a nitrogen-fixing bacterium isolated
      from cyanobacterial aggregates in a eutrophic lake.
AB  - A Gram-stain-negative, slightly curved rod-shaped, non-spore-forming diazotrophic
      bacterium, designated strain TH16T, was isolated from cyanobacterial aggregates
      taken from eutrophic Lake Taihu, Jiangsu Province, China. The pH range for growth
      was 5-9 (optimum at pH 7.0), salinity range was 0-2% (w/v) NaCl (optimum 0%) and
      temperature range was 20-37  degrees C (optimum 30  degrees C) in nutrient broth.
      Phylogenetic analysis indicated that strain TH16T clusters near and is closely
      related to the genus Niveispirillum within the family Rhodospirillaceae of the
      class Alphaproteobacteria. Within the genus Niveispirillum, strain TH16T was
      related most closely to Niveispirillum irakense KBC1T (98.1% 16S rRNA gene
      sequence similarity) and Niveispirillum fermenti CC-LY736T (97.0 %). The DNA G+C
      content of strain TH16T was 64 mol%. DNA-DNA relatedness between strain TH16T and
      the type strains of N. irakense and N. fermenti was 39.6 and 30.1%, respectively.
      The major respiratory quinone was ubiquinone Q-10.The major fatty acids (>10%)
      were C18  :  1omega6c/C18  :  1omega7c, C18  :  1 2-OH and C16  :  0 3-OH. Genes
      in the puf operon, encoding proteins of the photosynthetic reaction centre and
      core light-harvesting complexes, were also present. Based on morphological,
      chemotaxonomic and phylogenetic data, strain TH16T represents a novel species
      within the genus Niveispirillum, for which the name Niveispirillum
      cyanobacteriorum sp. nov. is proposed. The type strain is TH16T ( = CGMCC
      1.12958T = LMG 28334T).

PMID- 25944810
TI  - Study of the art: canine olfaction used for cancer detection on the basis of
      breath odour. Perspectives and limitations.
AB  - Experimental studies using trained dogs to identify breath odour markers of human
      cancer, published in the recent decade, have been analyzed and compared with the
      authors' own results. Particular published studies differ as regards the
      experimental setup, kind of odour samples (breath, urine, tumor tissue, serum),
      sample collection methods, dogs' characteristics and dog training methods as well
      as in results presented in terms of detection sensitivity and specificity.
      Generally it can be stated that trained dogs are able to distinguish breath odour
      samples typical for patients with lung cancer and other cancers from samples
      typical for healthy humans at a 'better than by chance' rate. Dogs' indications
      were positively correlated with content of 2-pentanone and ethyl acetate (r =
      0.97 and r = 0.85 respectively) and negatively correlated with 1-propanol and
      propanal in breath samples (r = -0.98 and -0.87 respectively). The canine method
      has some advantages as a potential cancer-screening method, due to its non
      invasiveness, simplicity of odour sampling and storage, ease of testing and
      interpretation of results and relatively low costs. Disadvantages and limitations
      of this method are related to the fact that it is still not known exactly to
      which chemical compounds and/or their combinations the dogs react. So far it
      could not be confirmed that dogs are able to sniff out early preclinical cancer
      stages with approximately the same accuracy as already diagnosed cases. The
      detection accuracy may vary due to failure in conditioning of dogs, decreasing
      motivation or confounding factors. The dogs' performance should be systematically
      checked in rigorous double-blind procedures. Recommendations for methodological
      standardization have been proposed.

PMID- 25944811
TI  - The compositional space of exhaled breath condensate and its link to the human
      breath volatilome.
AB  - Breath analysis is commonly understood to target gaseous or volatile organic
      compounds (VOCs) for the characterization of different pathologies. Targeted
      analysis is most effective if a working hypothesis can be based on a plethora of
      data. The recently published volatilome builds an optimal basis for organizing
      powerful target sets. However, the origin and pathways of biosynthesis of many
      VOCs are not known, which complicates the formulation of useful hypotheses. To
      find the missing link between VOCs and their origin, it is necessary to analyze
      their precursor fluids themselves. In order to provide condensation nuclei for
      the generation of future hypotheses, we provide the compositional space over 23
      samples of the unperturbed human exhaled breath condensate (EBC) metabolome. We
      propose a way to connect the compositional spaces of both VOCs and EBC so as to
      gain insight into the most probable form of VOC precursors. In a way analogous to
      tandem MS it is possible to create a mass difference network over compositional
      data by linking compositions with mass differences that are designed to mimic
      biochemical reactions. We propose to use mass difference enrichment analysis
      (MDEA) in order to mine probable relations between VOCs and their precursor
      fluids. We have found 2691 EBC compositions and linked them to 235 breath VOC
      compositions that correspond to 848 individual compounds. We found that VOCs are
      likely to be found as hexose conjugates or as amino acid conjugates with
      Glutamine or Asparagine playing a major role. Furthermore, we found that
      dicarboxylic acid mass differences may be more indicative for oxidative stress
      than oxygenation-hydrogenation sequences. 

PMID- 25944812
TI  - Application of an artificial neural network model for selection of potential lung
      cancer biomarkers.
AB  - Determination of volatile organic compounds (VOCs) in the exhaled breath samples
      of lung cancer patients and healthy controls was carried out by SPME-GC/MS (solid
      phase microextraction- gas chromatography combined with mass spectrometry)
      analyses. In order to compensate for the volatile exogenous contaminants, ambient
      air blank samples were also collected and analyzed. We recruited a total of 123
      patients with biopsy-confirmed lung cancer and 361 healthy controls to find the
      potential lung cancer biomarkers. Automatic peak deconvolution and identification
      were performed using chromatographic data processing software (AMDIS with NIST
      database). All of the VOCs sample data operation, storage and management were
      performed using the SQL (structured query language) relational database. The
      selected eight VOCs could be possible biomarker candidates. In cross-validation
      on test data sensitivity was 63.5% and specificity 72.4% AUC 0.65. The low
      performance of the model has been mainly due to overfitting and the exogenous
      VOCs that exist in breath. The dedicated software implementing a multilayer
      neural network using a genetic algorithm for training was built. Further work is
      needed to confirm the performance of the created experimental model. 

PMID- 25944813
TI  - Intravenous dexketoprofen vs placebo for migraine attack in the emergency
      department: A randomized, placebo-controlled trial.
AB  - OBJECTIVE: Migraine is a leading headache etiology that frequently presents to
      the emergency department (ED). In the present study, we aimed to determine the
      efficacy of dexketoprofen in aborting migraine headaches in the ED. METHODS: This
      prospective, randomized, double-blind study was conducted in an ED of a tertiary
      care hospital using allocation concealment. Patients were allocated into two arms
      to receive the study drug; 50 mg dexketoprofen in 50 ml saline and 50 ml saline
      as placebo. Change in pain intensity was measured by the visual analog scale at
      baseline, both at 30 and 45 minutes after the study medication was administered.
      Rescue medication requirement and pain relapse were also recorded by a telephone
      follow-up at 48 hours. RESULTS: A total of 224 patients (112 in each group) were
      included into the final analysis. Mean age of the study participants was 37 +/-
      11 (SD) and 25% (n = 56) of them were male. The median pain improvement at 45
      minutes for patients receiving dexketoprofen was 55 (IQR: 49 to 60) and 30 (IQR:
      25 to 35) for those receiving placebo. The mean difference between the two groups
      at 45 minutes was 21.4 (95% CI: 14.4. to 28.5). Rescue drugs were needed in 22.3%
      of patients who received dexketoprofen compared to 55.4% in patients who received
      placebo (dif: 33.1%; 95% CI: 20% to 45%). There were no adverse events reported
      in either group during the study period. CONCLUSION: Intravenous dexketoprofen is
      superior to placebo in relieving migraine headaches in the ED. It may be a
      suitable therapy with minimum side effects in patients presenting with a migraine
      headache to the ED.

PMID- 25944814
TI  - Variability of clinical features in attacks of migraine with aura.
AB  - BACKGROUND: There is significant variability in the clinical presentation of
      migraine, both among patients, and between attacks in an individual patient. We
      examined clinical features of migraine with aura in a large group of patients
      enrolled in a clinical trial, and compared retrospective migraine attack
      characteristics reported upon enrollment in the trial with those recorded
      prospectively in the trial. METHODS: Patients with migraine (n = 267) with
      typical visual aura in more than 30% of their attacks were enrolled from 16
      centers for a clinical trial. Upon enrollment, patients provided a detailed
      retrospective description of the clinical features of their attacks of migraine.
      During the trial, clinical symptoms in migraine attacks starting with aura were
      recorded prospectively in 861 attacks. RESULTS: Retrospectively reported visual
      aura symptoms were variable and often overlapping; the most common symptoms were
      dots or flashing lights, wavy or jagged lines, blind spots, and tunnel vision.
      Multiple patients reported more than one visual phenomenon. Approximately half of
      the patients reported nonvisual aura symptoms, the most common were numbness and
      tingling, followed by difficulty in recalling or speaking words. A significant
      percentage of patients also reported a change in olfaction. There were several
      inconsistencies between the features of prospectively recorded and
      retrospectively reported attacks. Headache, nausea, photophobia, and phonophobia
      were all less common in prospectively recorded attacks as compared with
      retrospective reporting. Nausea was prospectively recorded in only 51% of attacks
      and mostly with mild intensity. The occurrence and severity of nausea was reduced
      with advancing patient age. Phonophobia was not consistently recorded in
      conjunction with photophobia. CONCLUSION: These findings are consistent with
      variable involvement of different brain regions during a migraine attack. The
      variable occurrence of nausea, and phonophobia in conjunction with photophobia,
      both defining features of migraine, may be an important consideration in
      designing clinical studies of migraine in which prospectively recorded attacks
      are diagnosed based on these clinical features.

PMID- 25944815
TI  - Telcagepant--almost gone, but not to be forgotten (invited editorial related to
      Ho et al., 2015).

PMID- 25944816
TI  - Reversible cerebral vasoconstriction syndrome in the context of recent cerebral
      venous thrombosis: Report of a case.
AB  - INTRODUCTION: Reversible cerebral constriction syndrome and cerebral venous
      thrombosis are two rare conditions. Reversible cerebral constriction syndrome
      affects the cerebral arteries and the pathology is still largely unknown. To
      date, no physiological link with cerebral venous thrombosis has been reported.
      CASE RESULTS: We report here the case of a 24-year-old woman who presented a
      reversible cerebral constriction syndrome in the setting of a cerebral venous
      thrombosis. Cerebral venous thrombosis had developed in her left lateral venous
      sinus, within the stent placed one year before, in order to treat an idiopathic
      intracranial hypertension. DISCUSSION: The co-occurrence of cerebral venous
      thrombosis and reversible cerebral constriction syndrome in the same patient
      raises the issue of a potential link between them. We discuss the potential
      common trigger factors in this case: recent hormonal therapy; intracranial
      hypotension iatrogenically induced by lumbar puncture.

PMID- 25944817
TI  - Treatment and prognosis of subdural hematoma in patients with spontaneous
      intracranial hypotension.
AB  - OBJECTIVE: The objective of this article is to elucidate the outcome, prognostic
      predictors and timing of surgical intervention for subdural hematoma (SDH) in
      patients with spontaneous intracranial hypotension (SIH). METHODS: Patients with
      SDH were identified retrospectively from 227 consecutive SIH patients. Data were
      collected on demographics, clinical courses, neuroimaging findings, and treatment
      of SDH, which was later divided into conservative treatment, epidural blood
      patches (EBP), and surgical intervention. Poor outcome was defined as severe
      neurological sequelae or death. RESULTS: Forty-five patients (20%) with SDH (mean
      maximal thickness 11.9 +/- 6.2 mm) were recruited. All 15 patients with SDH <10
      mm achieved good outcomes by either conservative treatment or EBP. Of 30 patients
      with SDH >=10 mm, patients with uncal herniation (n = 3) had poor outcomes, even
      after emergent surgical evacuation (n = 2), compared to those without (n = 27)
      (100% vs. 0%, p < 0.001). Fourteen patients underwent surgical evacuation,
      resulting in good outcomes in all 12 who received early intervention and poor
      outcomes in the remaining two who received delayed intervention after Glasgow
      Coma Scale (GCS) score <=8 (100% vs. 0%, p = 0.01). CONCLUSIONS: Uncal herniation
      results in poor outcomes in patients with SIH complicated with SDH. In
      individuals with SDH >=10 mm and decreased GCS scores, early surgical evacuation
      might prevent uncal herniation.

PMID- 25944818
TI  - Meningeal transient receptor potential channel M8 activation causes cutaneous
      facial and hindpaw allodynia in a preclinical rodent model of headache.
AB  - BACKGROUND: Migraine headache is a neurological disorder affecting millions
      worldwide. However, little is known about the mechanisms contributing to
      migraine. Recent genome-wide association studies have found single nucleotide
      polymorphisms in the gene encoding transient receptor potential channel M8.
      Transient receptor potential channel M8 is generally known as a cold receptor but
      it has been implicated in pain signaling and may play a role in migraine pain.
      METHODS: In order to investigate whether transient receptor potential channel M8
      may contribute to the pain of migraine, the transient receptor potential channel
      M8 activator icilin was applied to the dura mater using a rat behavioral model of
      headache. Cutaneous allodynia was measured for 5 hours using Von Frey filaments.
      RESULTS: Dural application of icilin produced cutaneous facial and hind paw
      allodynia that was attenuated by systemic pretreatment with the transient
      receptor potential channel M8-selective antagonist AMG1161 (10 mg/kg p.o.).
      Further, the anti-migraine agent sumatriptan (0.6 mg/kg s.c.) or the non
      selective NOS inhibitor L-NAME (20 mg/kg i.p.) also attenuated allodynia when
      given as a pretreatment. CONCLUSIONS: These data indicate that transient receptor
      potential channel M8 activation in the meninges produces behaviors in rats that
      are consistent with migraine and that are sensitive to pharmacological mechanisms
      known to have efficacy for migraine in humans. The findings suggest that
      activation of meningeal transient receptor potential channel M8 may contribute to
      the pain of migraine.

PMID- 25944820
TI  - Resting heart rate on the decline: the Tromso Study 1986-2007.
AB  - BACKGROUND: We examined secular changes in resting heart rate (RHR) and their
      relationship with changes in other cardiovascular risk factors in adult men and
      women over a 22-year period. METHODS: A single-centre population-based
      longitudinal study comprised 30,699 men and women aged 30-89 years who
      participated in at least one of the 1986, 1994, 2001 and 2007 surveys of the
      Tromso Study, Tromso, Norway. RESULTS: During the study period, the age-adjusted
      means of RHR declined from 73.4 to 64.7 beats per minute (b.p.m.) in men, and
      from 78.3 to 66.4 b.p.m. in women. The decline was persistent from one survey to
      the next and was of similar size in both sexes and for all age groups and birth
      cohorts. RHR declined gradually over time for different levels of cardiovascular
      risk factors, and it declined more in those who moved from adverse to favourable
      values or categories of blood pressure, total and high-density lipoprotein
      cholesterol, triglycerides, body mass index, smoking and physical activity, and
      those who started to take blood pressure medication. The strongest predictors of
      individual decline in RHR were decrease in systolic blood pressure and
      triglycerides, increase in physical activity, taking blood pressure treatment and
      smoking cessation. CONCLUSION: A considerable decline in RHR has occurred in
      Tromso over the past two decades in men and women of all ages. The decline is
      partly related to changes in several cardiovascular risk factors, and reasons
      behind this need to be further elucidated. The findings suggest that new
      definitions of normal RHR may be needed.

PMID- 25944819
TI  - Early gestation as the critical time-window for changes in the prenatal
      environment to affect the adult human blood methylome.
AB  - BACKGROUND: The manipulation of pregnancy diets in animals can lead to changes in
      DNA methylation with phenotypic consequences in the offspring. Human studies have
      concentrated on the effects of nutrition during early gestation. Lacking in
      humans is an epigenome-wide association study of DNA methylation in relation to
      perturbations in nutrition across all gestation periods. METHODS: We used the
      quasi-experimental setting of the Dutch famine of 1944-45 to evaluate the impact
      of famine exposure during specific 10-week gestation periods, or during any time
      in gestation, on genome-wide DNA methylation levels at age ~ 59 years. In
      addition, we evaluated the impact of exposure during a shorter pre- and post
      conception period. DNA methylation was assessed using the Illumina 450k array in
      whole blood among 422 individuals with prenatal famine exposure and 463 time- or
      sibling-controls without prenatal famine exposure. RESULTS: Famine exposure
      during gestation weeks 1-10, but not weeks 11-20, 21-30 or 31-delivery, was
      associated with an increase in DNA methylation of CpG dinucleotides cg20823026
      (FAM150B), cg10354880 (SLC38A2) and cg27370573 (PPAP2C) and a decrease of
      cg11496778 (OSBPL5/MRGPRG) (P < 5.9 * 10(-7), PFDR < 0.031). There was an
      increase in methylation of TACC1 and ZNF385A after exposure during any time in
      gestation (P < 2.0 * 10(-7), PFDR = 0.034) and a decrease of cg23989336 (TMEM105)
      after exposure around conception. These changes represent a shift of 0.3-0.6
      standard deviations and are linked to genes involved in growth, development and
      metabolism. CONCLUSION: Early gestation, and not mid or late gestation, is
      identified as a critical time-period for adult DNA methylation changes in whole
      blood after prenatal exposure to famine.

PMID- 25944822
TI  - Towards high mobility InSb nanowire devices.
AB  - We study the low-temperature electron mobility of InSb nanowires. We extract the
      mobility at 4.2 K by means of field effect transport measurements using a model
      consisting of a nanowire-transistor with contact resistances. This model enables
      an accurate extraction of device parameters, thereby allowing for a systematic
      study of the nanowire mobility. We identify factors affecting the mobility, and
      after optimization obtain a field effect mobility of [Formula: see text] cm(2) V(
      1) s(-1). We further demonstrate the reproducibility of these mobility values
      which are among the highest reported for nanowires. Our investigations indicate
      that the mobility is currently limited by adsorption of molecules to the nanowire
      surface and/or the substrate. 

PMID- 25944821
TI  - Monitoring the ionic content of exhaled breath condensate in various respiratory
      diseases by capillary electrophoresis with contactless conductivity detection.
AB  - The analysis of an ionic profile of exhaled breath condensate (EBC) by capillary
      electrophoresis with contactless conductivity detection and double opposite end
      injection, is demonstrated. A miniature sampler made from a 2 ml syringe and an
      aluminium cooling cylinder was used for the fast collection of EBC (under one
      minute). Analysis of the collected EBC was performed in a 60 mM 2-(N
      morpholino)ethanesulfonic acid, 60 mM L-histidine background electrolyte with 30
      uM cetyltrimethylammonium bromide and 2 mM 18-crown-6 at pH 6, and excellent
      repeatability of migration times (RSD  <1.3% (n = 7)) and peak areas (RSD  <  7%
      (n = 7)) of 14 ions (inorganic anions, cations and organic acids) was obtained.
      It is demonstrated that the analysis of EBC samples obtained from patients with
      various respiratory diseases (chronic obstructive pulmonary disease, asthma,
      pulmonary fibrosis, sarcoidosis, cystic fibrosis) is possible in less than five
      minutes and the ionic profile can be compared with the group of healthy
      individuals. The analysis of the ionic profile of EBC samples provides a set of
      data in which statistically significant differences among the groups of patients
      could be observed for several clinically relevant anions (nitrite, nitrate,
      acetate, lactate). The developed collection system and method provides a highly
      reproducible and fast way of collecting and analyzing EBC, with future
      applicability in point-of-care diagnostics.

PMID- 25944823
TI  - Aqueous synthesis of near-infrared highly fluorescent platinum nanoclusters.
AB  - A one-step synthesis of near infrared fluorescent platinum nanoclusters (PtNCs)
      in aqueous medium is described. The proposed optimized procedure for PtNC
      synthesis is rather simple, fast and it is based on the direct metal reduction
      with NaBH4. Bidentated thiol ligands (lipoic acid) were selected as nanoclusters
      stabilizers in water media. The structural characterization revealed attractive
      features of the PtNCs, including small size, high water solubility, near-infrared
      luminescence centered at 680 nm, long-term stability and the highest quantum
      yield in water reported so far (47%) for PtNCs. Moreover, their stability in
      different pH media and an ionic strength of 0.2 M NaCl was studied and no
      significant changes in fluorescence emission were detected. In brief, they offer
      a new type of fluorescent noble metal nanoprobe with a great potential to be
      applied in several fields, including biolabeling and imaging experiments. 

PMID- 25944824
TI  - Quantitative Multilevel Analysis of Central Metabolism in Developing Oilseeds of
      Oilseed Rape during in Vitro Culture.
AB  - Seeds provide the basis for many food, feed, and fuel products. Continued
      increases in seed yield, composition, and quality require an improved
      understanding of how the developing seed converts carbon and nitrogen supplies
      into storage. Current knowledge of this process is often based on the premise
      that transcriptional regulation directly translates via enzyme concentration into
      flux. In an attempt to highlight metabolic control, we explore genotypic
      differences in carbon partitioning for in vitro cultured developing embryos of
      oilseed rape (Brassica napus). We determined biomass composition as well as 79
      net fluxes, the levels of 77 metabolites, and 26 enzyme activities with specific
      focus on central metabolism in nine selected germplasm accessions. Overall, we
      observed a tradeoff between the biomass component fractions of lipid and starch.
      With increasing lipid content over the spectrum of genotypes, plastidic fatty
      acid synthesis and glycolytic flux increased concomitantly, while glycolytic
      intermediates decreased. The lipid/starch tradeoff was not reflected at the
      proteome level, pointing to the significance of (posttranslational) metabolic
      control. Enzyme activity/flux and metabolite/flux correlations suggest that
      plastidic pyruvate kinase exerts flux control and that the lipid/starch tradeoff
      is most likely mediated by allosteric feedback regulation of phosphofructokinase
      and ADP-glucose pyrophosphorylase. Quantitative data were also used to calculate
      in vivo mass action ratios, reaction equilibria, and metabolite turnover times.
      Compounds like cyclic 3',5'-AMP and sucrose-6-phosphate were identified to
      potentially be involved in so far unknown mechanisms of metabolic control. This
      study provides a rich source of quantitative data for those studying central
      metabolism. 

PMID- 25944826
TI  - WHIRLY1 Functions in the Control of Responses to Nitrogen Deficiency But Not
      Aphid Infestation in Barley.
AB  - WHIRLY1 is largely targeted to plastids, where it is a major constituent of the
      nucleoids. To explore WHIRLY1 functions in barley (Hordeum vulgare), RNA
      interference-knockdown lines (W1-1, W1-7, and W1-9) that have very low levels of
      HvWHIRLY1 transcripts were characterized in plants grown under optimal and stress
      conditions. The WHIRLY1-1 (W1-1), W1-7, and W1-9 plants were phenotypically
      similar to the wild type but produced fewer tillers and seeds. Photosynthesis
      rates were similar in all lines, but W1-1, W1-7, and W1-9 leaves had
      significantly more chlorophyll and less sucrose than the wild type. Transcripts
      encoding specific subsets of chloroplast-localized proteins, such as ribosomal
      proteins, subunits of the RNA polymerase, and thylakoid nicotinamide adenine
      dinucleotide (reduced) and cytochrome b6/f complexes, were much more abundant in
      the W1-7 leaves than the wild type. Although susceptibility of aphid (Myzus
      persicae) infestation was similar in all lines, the WHIRLY1-deficient plants
      showed altered responses to nitrogen deficiency, maintaining higher
      photosynthetic CO2 assimilation rates than the wild type under limiting nitrogen.
      Although all lines showed globally similar low nitrogen-dependent changes in
      transcripts and metabolites, the increased abundance of FAR-RED IMPAIRED
      RESPONSE1-like transcripts in nitrogen-deficient W1-7 leaves infers that WHIRLY1
      has a role in communication between plastid and nuclear genes encoding
      photosynthetic proteins during abiotic stress. 

PMID- 25944825
TI  - An Overdose of the Arabidopsis Coreceptor BRASSINOSTEROID INSENSITIVE1-ASSOCIATED
      RECEPTOR KINASE1 or Its Ectodomain Causes Autoimmunity in a SUPPRESSOR OF BIR1-1
      Dependent Manner.
AB  - The membrane-bound Brassinosteroid insensitive1-associated receptor kinase1
      (BAK1) is a common coreceptor in plants and regulates distinct cellular programs
      ranging from growth and development to defense against pathogens. BAK1 functions
      through binding to ligand-stimulated transmembrane receptors and activating their
      kinase domains via transphosphorylation. In the absence of microbes, BAK1
      activity may be suppressed by different mechanisms, like interaction with the
      regulatory BIR (for BAK1-interacting receptor-like kinase) proteins. Here, we
      demonstrated that BAK1 overexpression in Arabidopsis (Arabidopsis thaliana) could
      cause detrimental effects on plant development, including growth arrest, leaf
      necrosis, and reduced seed production. Further analysis using an inducible
      expression system showed that BAK1 accumulation quickly stimulated immune
      responses, even under axenic conditions, and led to increased resistance to
      pathogenic Pseudomonas syringae pv tomato DC3000. Intriguingly, our study also
      revealed that the plasma membrane-associated BAK1 ectodomain was sufficient to
      induce autoimmunity, indicating a novel mode of action for BAK1 in immunity
      control. We postulate that an excess of BAK1 or its ectodomain could trigger
      immune receptor activation in the absence of microbes through unbalancing
      regulatory interactions, including those with BIRs. Consistently, mutation of
      suppressor of BIR1-1, which encodes an emerging positive regulator of
      transmembrane receptors in plants, suppressed the effects of BAK1 overexpression.
      In conclusion, our findings unravel a new role for the BAK1 ectodomain in the
      tight regulation of Arabidopsis immune receptors necessary to avoid inappropriate
      activation of immunity.

PMID- 25944827
TI  - Low Sugar Is Not Always Good: Impact of Specific O-Glycan Defects on Tip Growth
      in Arabidopsis.

PMID- 25944829
TI  - Efficacy of a home-based educational strategy involving community health
      volunteers in improving self-care in patients with chronic heart failure in
      western Iran: A randomized controlled trial.
AB  - BACKGROUND: This study aimed to evaluate the effectiveness of a home-based
      educational strategy using community health volunteers (CHVs) in improving self
      care of patients with chronic heart failure (CHF) in comparison with an
      educational strategy using formal health professionals (FHPs) at hospital, and
      also with a control group receiving usual care in western Iran. METHODS AND
      RESULTS: A three-arm controlled trial randomly allocated 231 patients with CHF
      into a control group and two intervention groups undertaking two different
      educational approaches - a face-to-face education program by CHVs at the
      patients' homes and a formal education program using paid FHPs at hospital. Data
      obtained through interviewing patients before and two months after interventions
      were analyzed. Self-care components significantly increased after the
      intervention in both interventional groups compared to the control group
      (p<0.001). Differences between the two strategies were not significant, except
      for self-care confidence being greater in the groups exposed to the health
      professionals (p=0.004). The mean and standard deviation (SD) of the changes in
      self-maintenance, self-management and self- confidence score (each with a maximum
      score of 100) for the CHVs group were 26.2+/-12.7, 29.4+/-11 9.5+/-17; for the
      health professional group were 29.5+/-12, 31.3+/-12, 18.1+/-17; and for the
      control group were 2.7+/-9, 10.2+/-10, -0.30+/-11 respectively. CONCLUSION: The
      home-based face-to-face education by CHVs improved self-care maintenance and self
      care management in patients with CHF as effectively as the education provided by
      health professionals in a formal health education program, and much better than
      the usual care.

PMID- 25944828
TI  - Group VII Ethylene Response Factors Coordinate Oxygen and Nitric Oxide Signal
      Transduction and Stress Responses in Plants.
AB  - The group VII ethylene response factors (ERFVIIs) are plant-specific
      transcription factors that have emerged as important regulators of abiotic and
      biotic stress responses, in particular, low-oxygen stress. A defining feature of
      ERFVIIs is their conserved N-terminal domain, which renders them oxygen- and
      nitric oxide (NO)-dependent substrates of the N-end rule pathway of targeted
      proteolysis. In the presence of these gases, ERFVIIs are destabilized, whereas an
      absence of either permits their accumulation; ERFVIIs therefore coordinate plant
      homeostatic responses to oxygen availability and control a wide range of NO
      mediated processes. ERFVIIs have a variety of context-specific protein and gene
      interaction partners, and also modulate gibberellin and abscisic acid signaling
      to regulate diverse developmental processes and stress responses. This update
      discusses recent advances in our understanding of ERFVII regulation and function,
      highlighting their role as central regulators of gaseous signal transduction at
      the interface of ethylene, oxygen, and NO signaling. 

PMID- 25944830
TI  - Bystander Sexual Violence Prevention Program: Outcomes for High- and Low-Risk
      University Men.
AB  - This research reports the findings of an evaluation of a peer-facilitated,
      bystander sexual violence prevention program to determine its effectiveness at
      changing attitudes and behaviors related to sexual violence with university males
      who are at low- and high-risk of using sexually coercive behavior. Bystander
      interventions focus on men and women as bystanders to change social norms in a
      peer culture that supports abusive behaviors. Few studies have examined the
      effectiveness of these interventions with high-risk populations, which is the
      focus of this study. A bystander sexual violence prevention program was presented
      to 142 fraternity members. A quasi-experimental design utilizing pre-, post-, and
      follow-up surveys was used to compare the effectiveness of this prevention
      program with university males who are at low- and high-risk of using sexually
      coercive behavior in intervention and comparison groups. Participants' risk
      status was measured prior to the intervention using the Modified-Sexual
      Experiences Survey. The measures evaluated changes in attitudes (rape myth
      acceptance and bystander attitudes) and behaviors (sexually coercive behaviors,
      sexually coercive behavioral intentions, and bystander behaviors). Data analyses
      included Repeated-Measures Analysis of Covariances. The findings suggest that a
      bystander sexual violence prevention program has a positive impact on attitudes
      and behaviors related to sexual violence among fraternity members, however, the
      program had less impact on high-risk males. The results of this study will expand
      our ability to design programs that can have an impact on reducing sexual
      violence on campus by ensuring the programs are having the desired impact on the
      target audience.

PMID- 25944831
TI  - Research Reactions Following Participation in Intimate Partner Violence Research:
      An Examination With Men in Substance Use Treatment.
AB  - There has been increased attention in recent years related to the research
      reactions of individuals who participate in intimate partner violence (IPV)
      research. Existing studies demonstrate that participating in IPV research is not
      emotionally upsetting for the vast majority of participants and that many
      participants perceive benefit from their research participation. However, almost
      all of the existing research has utilized non-clinical samples or battered women,
      failing to examine the research reactions of a clinical sample of men. Thus, the
      present study examined the research reactions of men in substance use treatment (
      N = 138) who completed a self-report measure of IPV perpetration and
      victimization. We also examined whether distress tolerance moderated the
      relationship between reports of IPV and negative emotional research reactions.
      Consistent with previous research, after accounting for distress tolerance,
      substance use, and demographic control variables, IPV was unrelated to negative
      emotional research reactions. Distress tolerance did not moderate the association
      between IPV and research reactions. Findings add to a growing body of literature
      suggesting that IPV research meets Institutional Review Board (IRB) requirements
      for minimal risk research.

PMID- 25944833
TI  - Intimate Partner Violence Among Pregnant Young Women: A Qualitative Inquiry.
AB  - This article explores intimate partner violence (IPV) as experienced by young
      women during the perinatal period. Using purposive sampling, data pertaining to
      the experiences of 10 young mothers were gathered through on-site participative
      observation and individual in-depth interviews. Interviews were coded in an
      inductive way to reflect the experiences of the participants before pregnancy and
      following pregnancy confirmation. Overall, the analyses of different
      manifestations of IPV and their contexts reveal the difficulty these young
      mothers experience in identifying themselves as a victim of IPV and in
      categorizing their partner's acts as intimate violence. The fear of family
      separation and the desire to protect their child contributed to the complexity of
      violence experienced in a context of motherhood. This article also reflects on
      the limits of data collection on this subject through comparison of the results
      of the interviews with the results of the Revised Conflict Tactics Scale (CTS-2).
      Further research is needed to provide more insight into victimization among young
      mothers and to inform interventions with the goal of helping young women overcome
      the intersecting challenges of violence and motherhood.

PMID- 25944832
TI  - Youth Violence: How Gender Matters in Aggression Among Urban Early Adolescents.
AB  - Although research suggests gender differences in both forms and functions of
      aggressive behavior, there has been limited research into these types among
      African American early adolescents. This study examined the types and patterns of
      aggression in girls and boys in that group. Participants were 452 predominantly
      African American middle school youth (50.4% girls) aged 11 to 13 ( M = 11.97)
      enrolled in three urban public schools. Students were invited to participate in a
      school-based intervention designed to prevent aggressive and deviant behaviors.
      Assessments occurred pre- and post-intervention. Surveys were analyzed to
      identify gender differences in the levels and types of aggressive behaviors, as
      well as differences in predictors of aggressive behaviors. Predictors were
      measured at baseline; aggressive behaviors at follow-up. There were significant
      gender differences in types of aggressive behaviors and their predictors
      indicating a need to develop and implement more suitable, gender-tailored
      prevention and treatment approaches.

PMID- 25944834
TI  - Experiences of Online Harassment Among Emerging Adults: Emotional Reactions and
      the Mediating Role of Fear.
AB  - Online harassment is a growing problem. Among college students, 43% report some
      experience receiving harassing messages. Previous research has shown negative
      online experiences to be typical among "emerging adults" (especially college
      students), and these incidents may be related to normative developmental
      behaviors, such as "on-again-off-again" romantic relationships. Study hypotheses
      were derived from previous research. Undergraduate student respondents ( N = 342)
      were surveyed about their experiences with online harassment, emotional responses
      to online harassment, and their relationship with the sender of harassing
      messages. Findings suggest that online harassment is linked to issues of intimate
      partner violence. Those who were harassed by a partner reported feelings of
      depression and anxiety. Using a gendered framework to explore online harassment
      is warranted because young women who are 18 to 29 years of age have higher rates
      of intimate partner violence than other demographic groups. Findings suggest
      future research is needed to understand the time ordering of these issues.

PMID- 25944835
TI  - From Sexual Assault to Sexual Risk: A Relational Pathway?
AB  - Among women and gay and bisexual men, sexual assault is associated with increased
      rates of sexual risk behavior and negative sexual health outcomes. Although the
      mechanisms of these effects are potentially myriad, the current analyses examine
      the role of perceived partner pressure for condomless sex in mediating the
      association between adult sexual assault (ASA) and recent anal or vaginal sex
      without a condom. In a sample of 205 young adult women and gay and bisexual men,
      ASA was indirectly associated with condomless anal and/or vaginal sex via
      perceptions of partner pressure for condomless sex, chi2(1) = 5.66, p = .02,
      after controlling for race, age, gender and sexual identity, and relationship
      status. The elucidation of this relational mechanism points to several potential
      intervention and prevention strategies that may reduce actual and perceived
      pressure for sex without a condom, including strategies designed to facilitate
      the prioritization of health and safety over relational goals and the improvement
      of partner selection and perceptions of partner pressure.

PMID- 25944836
TI  - Bystander Intervention Among College Men: The Role of Alcohol and Correlates of
      Sexual Aggression.
AB  - Current efforts to reduce sexual violence in college campuses underscore the role
      of engaging men in prosocial bystander behavior. The current study implemented an
      online survey to explore associations between engaging in heavy drinking and
      attitudes toward bystander intervention among a sample of college men (N = 242).
      Correlates of sexual aggression were also explored as mediators of the
      hypothesized relationship between engaging in heavy drinking and attitudes toward
      bystander intervention. Data indicated that men who engaged in two or more
      episodes of heavy drinking over the past month reported lower prosocial bystander
      attitudes compared with men who did not engage in such behavior. The association
      between engaging in heavy drinking and lower prosocial bystander attitudes was
      mediated by men's perception of their peers' approval for sexual aggression,
      their own comfort with sexism, and engagement in coercive sexual behavior.
      Implications for sexual assault prevention are discussed.

PMID- 25944837
TI  - Impeaching Rape Victims in Criminal Court: Does Concurrent Civil Action Hurt
      Justice?
AB  - The present study investigated the impact of impeaching a rape victim with
      evidence of a simultaneous civil suit during a criminal trial. In three
      experiments, male and female undergraduates (Experiment 1) and community members
      (Experiments 2 and 3) read a rape trial summary in which the victim accused the
      defendant of raping her in a hotel. In the impeachment condition, the Defense
      mentioned that the victim simultaneously sued either the hotel (Experiments 1, 2,
      3) or the alleged perpetrator (Experiment 3) for US$1 million. In the control
      condition, the Defense did not mention a civil suit. In all experiments, mock
      jurors were more likely to render not guilty verdicts and had higher pro
      defendant ratings (e.g., defendant credibility) when the Defense impeached the
      victim than when the Defense did not impeach her. In addition, victim credibility
      (Experiments 1, 2, 3) and victim greed (Experiment 3) mediated the impact of
      impeachment on verdict. Results are discussed in terms of the prejudice rape
      victims may face in criminal court when they also seek justice in civil court.

PMID- 25944838
TI  - Structural and compositional evolutions of InxAl1-xN core-shell nanorods grown on
      Si(111) substrates by reactive magnetron sputter epitaxy.
AB  - Catalystless growth of InxAl(1-x)N core-shell nanorods have been realized by
      reactive magnetron sputter epitaxy onto Si(111) substrates. The samples were
      characterized by scanning electron microscopy, x-ray diffraction, scanning
      transmission electron microscopy, and energy dispersive x-ray spectroscopy. The
      composition and morphology of InxAl(1-x)N nanorods are found to be strongly
      influenced by the growth temperature. At lower temperatures, the grown materials
      form well-separated and uniform core-shell nanorods with high In-content cores,
      while a deposition at higher temperature leads to the formation of an Al-rich
      InxAl(1-x)N film with vertical domains of low In-content as a result of merging
      Al-rich shells. The thickness and In content of the cores (domains) increase with
      decreasing growth temperature. The growth of the InxAl(1-x)N is traced to the
      initial stage, showing that the formation of the core-shell nanostructures starts
      very close to the interface. Phase separation due to spinodal decomposition is
      suggested as the origin of the resultant structures. Moreover, the in-plane
      crystallographic relationship of the nanorods and substrate was modified from a
      fiber textured to an epitaxial growth with an epitaxial relationship of InxAl(1
      x)N[0001]//Si[111] and InxAl(1-x)N[1120]//Si[110 by removing the native SiOx
      layer from the substrate.

PMID- 25944839
TI  - Low interfacial contact resistance of Al-graphene composites via interface
      engineering.
AB  - Al-based composites incorporating multilayered graphene sheets were developed via
      a facile approach. The multilayered graphene sheets were fabricated from the
      expanded graphite via a simple mechanical exfoliation process. The facile
      extrusion molding process with Al powder and graphene sheets exfoliated from
      expended graphite afforded Al-based graphene composite rods. These composites
      showed enhanced thermal conductivity compared to the pristine Al rods. Moreover,
      the Al-based multilayered graphene sheet composites exhibited lower interfacial
      contact resistance between graphene-based electrodes than the pristine Al. With
      increasing degrees of dispersion, the number of exposed graphene sheets
      increases, thereby significantly decreasing the interfacial contact resistance
      between the composite and external graphite electrode. 

PMID- 25944840
TI  - Numerical Simulation on the Response Characteristics of a Pneumatic Microactuator
      for Microfluidic Chips.
AB  - This article presents a multiphysical system modeling and simulation of a
      pneumatic microactuator, which significantly influences the performance of a
      particular pneumatic microfluidic device. First, the multiphysical system
      modeling is performed by developing a physical model for each of its three
      integrated components: microchannel with a microvalve, a gas chamber, and an
      elastomer membrane. This is done for each step of operation for the whole system.
      The whole system is then considered a throttle blind capacitor model, and it is
      used to predict the response time of the pneumatic microactuator by correlating
      its characteristics such as gas pressurizing, hydraulic resistance, and membrane
      deformation. For this microactuator, when the maximum membrane deformation is 100
      um, the required actuated air pressure is 80 kPa, and the response time is 1.67
      ms when the valve-opening degree is 0.8. The response time is 1.61 ms under fully
      open conditions. These simulated results are validated by the experimental
      results of the current and previous work. A correlation between the simulated and
      experimental results confirms that the multiphysical modeling presented in this
      work is applicable in developing a proper design of a pneumatic microactuator.
      Finally, the influencing factors of the response time are discussed and analyzed.

PMID- 25944841
TI  - Correction for Xing et al., The Z Proteins of Pathogenic but Not Nonpathogenic
      Arenaviruses Inhibit RIG-i-Like Receptor-Dependent Interferon Production.

PMID- 25944843
TI  - A Nuclear Magnetic Resonance Spectroscopy as a Method for Evaluation of In Vivo
      Poly-l-Lactide Biodegradation Kinetics From Stent-Polymer Matrices: An
      Experimental Study Utilizing Porcine Model of In-Stent Restenosis.
AB  - OBJECTIVES: We aimed to comprehensively evaluate poly-lactide polymer degradation
      and sirolimus release kinetics from a drug-eluting stent matrix in the in vivo
      setting using a nuclear magnetic resonance (NMR) method. METHODS: In 22 domestic
      swine, 18 biodegradable polymer-only coated stents (BPSs) and 36 biodegradable
      polymer-coated sirolimus-eluting stents (BP-SES) were implanted in coronary
      arteries with 115% overstretch. The animals were sacrificed at 1, 3, 7, 14, 28,
      and 56 days following baseline procedures. Vessel segments with BPS were
      harvested to evaluate polymer degradation with a NMR method, whereas BP-SES to
      analyze sirolimus tissue uptake and retention. Additionally, 8 BP-SES were
      implanted for histological analysis for 90 days of follow-up. RESULTS: The NMR
      showed a gradual absorption of the polymer over the 6 consecutive time points,
      from 5.48 ug of the polymer on the stent at 1-day follow-up, through 4.33 ug at 3
      days, 3.16 ug at 7 days, 2.42 ug at 14 days, 1.92 ug at 28 days to 1.24 ug in the
      last day of the study. The curve of polymer degradation corresponds well with the
      pharmacokinetic profile of sirolimus eluted from its surface and measured at
      identical time points. In histopathology, at 90 days, complete healing and
      biocompatibility were reported. CONCLUSIONS: The utilization of NMR method for BP
      absorption kinetics evaluation is a useful tool, which may be widely adopted to
      test other biodegradable implants. Further, it may substantially improve their
      safety and efficacy by facilitating programmed polymer and drugs elution.

PMID- 25944844
TI  - Melatonin Attenuates Aortic Endothelial Permeability and Arteriosclerosis in
      Streptozotocin-Induced Diabetic Rats: Possible Role of MLCK- and MLCP-Dependent
      MLC Phosphorylation.
AB  - The development of diabetic macrovascular complications is a multifactorial
      process, and melatonin may possess cardiovascular protective properties. This
      study was designed to evaluate whether melatonin attenuates arteriosclerosis and
      endothelial permeability by suppressing the myosin light-chain kinase
      (MLCK)/myosin light-chain phosphorylation (p-MLC) system via the mitogen
      activated protein kinase (MAPK) signaling pathway or by suppressing the myosin
      phosphatase-targeting subunit phosphorylation (p-MYPT)/p-MLC system in diabetes
      mellitus (DM). Rats were randomly divided into 4 groups, including control, high
      fat diet, DM, and DM + melatonin groups. Melatonin was administered (10 mg/kg/d)
      by gavage for 12 weeks. The DM significantly increased the serum fasting blood
      glucose and lipid levels, as well as insulin resistance and endothelial
      dysfunction, which were attenuated by melatonin therapy to various extents.
      Importantly, the aortic endothelial permeability was significantly increased in
      DM rats but was dramatically reversed following treatment with melatonin. Our
      findings further indicated that hyperglycemia and hyperlipidemia enhanced the
      expressions of MLCK, p-MYPT, and p-MLC, which were partly associated with
      decreased membrane type 1 expression, increased extracellular signal-regulated
      kinase (ERK) phosphorylation, and increased p38 expression. However, these
      changes in protein expression were also significantly reversed by melatonin.
      Thus, our results are the first to demonstrate that the endothelial
      hyperpermeability induced by DM is associated with increased expressions of MLCK,
      p-MYPT, and p-MLC, which can be attenuated by melatonin at least partly through
      the ERK/p38 signaling pathway. 

PMID- 25944845
TI  - Men's Health Is Not Affected by Their Mothers' Intrahepatic Cholestasis of
      Pregnancy.
AB  - Little is known about the effects of mother's intrahepatic cholestasis of
      pregnancy (ICP) on the health of sons born to these mothers. The purpose of the
      present study was to explore the health of sons born to mothers with ICP. The
      study design was a retrospective study of ICP mothers' sons. In the region of
      Tampere University Hospital in Finland, 365 sons of mothers with ICP during 1969
      to 1988 and 617 sons of mothers without ICP were sent a questionnaire in 2010.
      The response rates were 37.8% (n = 138) and 36.6% (n = 226), respectively. Only
      minor differences were reported between the two groups. Self-evaluated health was
      similar. There were no significant differences between the groups regarding
      symptoms and complaints, diagnosed diseases, mental health, and use of medicines.
      Cough was 10.8 percentage points less common among ICP mothers' sons than among
      controls (p = .034). Urticaria was more common among ICP mothers' sons, the
      difference in percentage points being 2.2 (p = .026). In general, a mother's ICP
      does not affect her son's health.

PMID- 25944847
TI  - Global surgery.

PMID- 25944846
TI  - Estrogen regulates luminal progenitor cell differentiation through H19 gene
      expression.
AB  - Although the role of estrogen signaling in breast cancer development has been
      extensively studied, the mechanisms that regulate the indispensable role of
      estrogen in normal mammary gland development have not been well studied. Because
      of the unavailability of culture system to maintain estrogen-receptor-positive
      (ERalpha(+)) cells in vitro, the molecular mechanisms that regulate
      estrogen/ERalpha signaling in the normal human breast are unknown. In the present
      study, we examined the effects of estrogen signaling on ERalpha(+) human luminal
      progenitors using a modified matrigel assay and found that estrogen signaling
      increased the expansion potential of these progenitors. Furthermore, we found
      that blocking ERalpha attenuated luminal progenitor expansion and decreased the
      luminal colony-forming potential of these progenitors. Additionally, blocking
      ERalpha decreased H19 expression in the luminal progenitors and led to the
      development of smaller luminal colonies. We further showed that knocking down the
      H19 gene in the luminal progenitors significantly decreased the colony-forming
      potential of the luminal progenitors, and this phenotype could not be rescued by
      the addition of estrogen. Lastly, we explored the clinical relevance of the
      estrogen-H19 signaling axis in breast tumors and found that ERalpha(+) tumors
      exhibited a higher expression of H19 as compared with ERalpha(-) tumors and that
      H19 expression showed a positive correlation with ERalpha expression in those
      tumors. Taken together, the present results indicate that the estrogen-ERalpha
      H19 signaling axis plays a role in regulating the proliferation and
      differentiation potentials of the normal luminal progenitors and that this
      signaling network may also be important in the development of ER(+) breast cancer
      tumors. 

PMID- 25944849
TI  - Polygenic risk scores in imaging genetics: Usefulness and applications.
AB  - Genetic factors account for up to 80% of the liability for schizophrenia and
      bipolar disorder. Genome-wide association studies (GWAS) have successfully
      identified several single nucleotide polymorphisms (SNPs) and genes associated
      with increased risk for both disorders. Single SNP analyses alone do not address
      the overall genomic or polygenic architecture of psychiatric disorders as the
      amount of phenotypic variation explained by each GWAS-supported SNP is small
      whereas the number of SNPs/regions underlying risk for illness is thought to be
      very large. The polygenic risk score models the aggregate effect of alleles
      associated with disease status present in each individual and allows us to
      utilise the power of large GWAS to be applied robustly in small samples. Here we
      make the case that risk prediction, intervention and personalised medicine can
      only benefit with the inclusion of polygenic risk scores in imaging genetics
      research. 

PMID- 25944848
TI  - Genome-wide association study identifies common variants associated with
      pharmacokinetics of psychotropic drugs.
AB  - Individual variation in pharmacokinetics of psychotropic drugs, particularly
      metabolism, is an important factor to consider in pharmacological treatment in
      psychiatry. A large proportion of this variance is still not accounted for, but
      evidence so far suggests the involvement of genetic factors. We performed a
      genome-wide association study (GWAS) with concentration dose ratio (CDR) as sub
      phenotype to assess metabolism rate of psychotropic drugs in a homogenous
      Norwegian sample of 1334 individuals diagnosed with a severe mental disorder. The
      GWAS revealed one genome-wide significant marker (rs16935279, p-value=3.95*10(
      10), pperm=7.5*10(-4)) located in an intronic region of the lncRNA LOC100505718.
      Carriers of the minor allele have a lower metabolism rate of antiepileptic drugs
      compared to major allele carriers. In addition, several nominally significant
      associations between single nucleotide polymorphisms (SNPs) and CDR for
      antipsychotic, antidepressant and antiepileptic drugs were disclosed. We consider
      standardised CDR to be a useful measure of the metabolism rate of a drug. The
      present findings indicate that common gene variants could affect the metabolism
      of psychotropic drugs. This warrants further investigations into the functional
      mechanisms involved as it may lead to identification of predictive markers as
      well as novel drug targets. 

PMID- 25944850
TI  - A non-parametric model to address overdispersed count response in a longitudinal
      data setting with missingness.
AB  - Count responses are becoming increasingly important in biostatistical analysis
      because of the development of new biomedical techniques such as next-generation
      sequencing and digital polymerase chain reaction; a commonly met problem in
      modeling them with the popular Poisson model is overdispersion. Although it has
      been studied extensively for cross-sectional observations, addressing
      overdispersion for longitudinal data without parametric distributional
      assumptions remains challenging, especially with missing data. In this paper, we
      propose a method to detect overdispersion in repeated measures in a non
      parametric manner by extending the Mann-Whitney-Wilcoxon rank sum test to
      longitudinal data. In addition, we also incorporate the inverse probability
      weighted method to address the data missingness. The proposed model is
      illustrated with both simulated and real study data.

PMID- 25944851
TI  - Regular exercise improves weight stability in patients with advanced heart
      failure.
AB  - OBJECTIVES: The purpose of this study was to determine if a progressive,
      prescribed home-based aerobic exercise program would alter the natural
      physiological processes that maintain fluid balance stability in patients with
      New York Heart Association (NYHA) class III/IV heart failure after medical
      optimization (titration of oral medical therapy with or without the infusion of
      an intravenous inotrope). METHODS: A total of 56 men and women from a large
      tertiary trauma I hospital were enrolled with 56 subjects contributing to
      baseline analysis and 42 subjects at 24 weeks. Subjects were diagnosed with heart
      failure via NYHA classification IV or III for at least 6 months and were
      hospitalized for a current acute decompensation exacerbation in which they were
      being medically optimized. The exercise intervention was a home-based,
      prescribed, progressive aerobic exercise program lasting for 24 weeks. The
      exercise participants had weekly phone calls to gather data and progress the
      exercise program and one 12-week follow up. The usual care participants received
      random phone calls to collect data and had one 12-week follow up visit to attain
      physical assessment values. RESULTS: Subjects were primarily female (59%),
      nonwhite (54%), and NYHA class IV (52%) versus class III (48%). The mean age was
      58 years (+/-11.8 years). The subjects had a mean ejection fraction of 17.7 % (+/
      7%) and mean maximal oxygen consumption of 12.1 (+/-3.4). Using a hierarchical
      multiple regression model, it was demonstrated that an exercise prescription
      (intensity, frequency, duration) significantly predicted 24 h weight fluctuations
      within a NYHA class III/IV heart failure population after medical optimization
      (R(2) linear = 0.713, F = 3.224, p = 0.015). CONCLUSION: This study demonstrated
      that exercise is a successful adjunctive therapy to managing the daily weight
      variability or fluid status instability of patients with NYHA class III/IV heart
      failure that is often a debilitating aspect of the syndrome.

PMID- 25944852
TI  - Association of polymorphisms in the AGT gene(M235T, T174M) with ischemic stroke
      in the Chinese population.
AB  - OBJECTIVE: The angiotensinogen (AGT) gene polymorphisms has been shown to be
      involved in the development of ischemic stroke. However, the published studies
      have yielded inconsistent results. We performed a meta-analysis to assess the
      correlation. METHODS: Published literature from PubMed, EMBASE, CNKI and Wanfang
      Data was searched. The association was assessed by odds ratio (OR) with 95%
      confidence intervals (CI). Publication bias was also calculated. RESULTS: Eight
      studies (1636 cases and 1433 controls) on M235T polymorphism and four studies
      (726 cases and 495 controls) on T174M polymorphism were included in the meta
      analysis. The results showed that M235T polymorphism was significantly associated
      with risk of ischemic stroke risk (TT vs. MM: OR=2.60, 95% CI=1.77-3.83; MT vs.
      MM: OR=1.37, 95% CI=1.01-1.86; TT+MT vs. MM: OR=0.43, 95% CI=0.35-0.54; MM+MT vs.
      TT: OR=1.74, 95% CI=1.31-2.32). There was also significant association between
      T174M polymorphism and ischemic stroke risk (MM vs. TT: OR=3.66, 95% CI=1.89
      7.08; TT+MT vs. MM: OR=0.28, 95% CI=0.14-0.54). Further sensitivity analysis
      confirmed the significant association between AGT gene polymorphisms and risk of
      ischemic stroke. No evidence indicated publication bias. CONCLUSIONS: The meta
      analysis indicated the significant association of AGT gene polymorphisms (M235T,
      T174M) with risk of ischemic stroke in the Chinese population.

PMID- 25944853
TI  - Cerebroprotective effects of RAS inhibitors: Beyond their cardio-renal actions.
AB  - Work on the brain renin-angiotensin system has been explored by various
      researchers and has led to elucidation of its basic physiologies and behavior,
      including its role in reabsorption and uptake of body fluid, blood pressure
      maintenance with angiotensin II being its prominent effector. Currently, this
      system has been implicated for its newly established effects, which are far
      beyond its cardio-renal effects accounting for maintenance of cerebral blood flow
      and cerebroprotection, seizure, in the etiology of Alzheimer's disease,
      Parkinson's disease, multiple sclerosis, and bipolar disorder. In this review, we
      have discussed the distribution of angiotensin receptor subtypes in the central
      nervous system (CNS) together with enzymatic pathways leading to active
      angiotensin ligands and its interaction with angiotensin receptor 2 (AT2) and Mas
      receptors. Secondly, the use of angiotensin analogues (angiotensin converting
      enzyme inhibitors and AT1 and/or AT2 receptor blockers) in the treatment and
      management of the CNS disorders mentioned above has been discussed. 

PMID- 25944854
TI  - Effects of treatment withdrawal on brachial and central aortic pressure after
      direct renin inhibition or angiotensin receptor blockade.
AB  - INTRODUCTION: Whilst sustained lowering of brachial systolic blood pressure (Br
      SBP) and central aortic systolic pressure (CASP) have been demonstrated in
      patients with hypertension, effects of treatment withdrawal on these parameters
      have not been investigated. The ASSERTIVE study previously reported more
      sustained control of Br-SBP with aliskiren versus telmisartan in patients with
      hypertension, following 7-days treatment withdrawal. In this ASSERTIVE sub-study,
      we hypothesised that aliskiren would similarly exert more sustained control of
      CASP than telmisartan during treatment withdrawal. METHODS: We investigated the
      effects of treatment withdrawal on both Br-SBP and CASP following 12-weeks
      treatment with either aliskiren (300 mg) or telmisartan (80 mg). Br-SBP and CASP
      were measured at the end of treatment, and at days 2 and 7 following treatment
      withdrawal in 303 patients (CASP randomised set). RESULTS: Of the CASP randomised
      set, 94 patients completed CASP measurements at all time points (CASP completer
      set). After 7 days of treatment withdrawal, aliskiren demonstrated lesser
      increases in both Br-SBP and CASP than telmisartan; Br-SBP change: -2.0+/-1.6 vs.
      +5.6+/-1.7 mmHg, p = 0.001; CASP change: -0.4+/-1.6 vs. +4.6+/-1.7 mmHg, p =
      0.041, n = 94. Similar findings were obtained for the CASP randomised set.
      CONCLUSIONS: Following treatment withdrawal, aliskiren demonstrated more
      sustained control of both brachial and central SBP than telmisartan.

PMID- 25944855
TI  - Establishment of a reference value for chromium in the blood for biological
      monitoring among occupational chromium workers.
AB  - The concentration of chromium in the blood (CrB) has been confirmed as a
      biomarker for occupational chromium exposure, but its biological exposure indices
      (BEIs) are still unclear, so we collected data from the years 2006 and 2008
      (Shandong Province, China) to analyze the relationship between the concentration
      of chromium in the air (CrA) of the workplaces and CrB to establish a reference
      value of CrB for biological monitoring of occupational workers. The levels of the
      indicators for nasal injury, kidney (beta2 microglobulin (beta2-MG)), and genetic
      damages (8-hydroxy-deoxyguanosine (8-OHdG) and micronucleus (MN)) were measured
      in all subjects of the year 2011 (Henan Province, China) to verify the protective
      effect in this reference value of CrB. Compared with the control groups, the
      concentrations of CrA and CrB in chromium exposed groups were significantly
      higher (P < 0.05). Positive correlations were found between CrA and CrB in
      chromium exposed groups (r 2006 = 0.60, r 2008 = 0.35) in the years 2006 and
      2008. According to the occupational exposure limitation of CrA (50 MUg/m(3),
      China), the reference value of CrB was recommended to 20 MUg/L. The levels of
      nasal injury, beta2-MG, 8-OhdG, and MN were not significantly different between
      the low chromium exposed group (CrB <= 20 MUg/L) and the control group, while the
      levels of beta2-MG, 8-OHdG, and MN were statistically different in the high
      chromium exposed group than that in the control group. This research proved that
      only in occupational workers, CrB could be used as a biomarker to show chromium
      exposure in the environment. The recommended reference value of CrB was 20 MUg/L.

PMID- 25944856
TI  - Nitric Oxide Mediates Biofilm Formation and Symbiosis in Silicibacter sp. Strain
      TrichCH4B.
AB  - Nitric oxide (NO) plays an important signaling role in all domains of life. Many
      bacteria contain a heme-nitric oxide/oxygen binding (H-NOX) protein that
      selectively binds NO. These H-NOX proteins often act as sensors that regulate
      histidine kinase (HK) activity, forming part of a bacterial two-component
      signaling system that also involves one or more response regulators. In several
      organisms, NO binding to the H-NOX protein governs bacterial biofilm formation;
      however, the source of NO exposure for these bacteria is unknown. In mammals, NO
      is generated by the enzyme nitric oxide synthase (NOS) and signals through
      binding the H-NOX domain of soluble guanylate cyclase. Recently, several
      bacterial NOS proteins have also been reported, but the corresponding bacteria do
      not also encode an H-NOX protein. Here, we report the first characterization of a
      bacterium that encodes both a NOS and H-NOX, thus resembling the mammalian system
      capable of both synthesizing and sensing NO. We characterized the NO signaling
      pathway of the marine alphaproteobacterium Silicibacter sp. strain TrichCH4B,
      determining that the NOS is activated by an algal symbiont, Trichodesmium
      erythraeum. NO signaling through a histidine kinase-response regulator two
      component signaling pathway results in increased concentrations of cyclic
      diguanosine monophosphate, a key bacterial second messenger molecule that
      controls cellular adhesion and biofilm formation. Silicibacter sp. TrichCH4B
      biofilm formation, activated by T. erythraeum, may be an important mechanism for
      symbiosis between the two organisms, revealing that NO plays a previously unknown
      key role in bacterial communication and symbiosis. IMPORTANCE: Bacterial nitric
      oxide (NO) signaling via heme-nitric oxide/oxygen binding (H-NOX) proteins
      regulates biofilm formation, playing an important role in protecting bacteria
      from oxidative stress and other environmental stresses. Biofilms are also an
      important part of symbiosis, allowing the organism to remain in a nutrient-rich
      environment. In this study, we show that in Silicibacter sp. strain TrichCH4B, NO
      mediates symbiosis with the alga Trichodesmium erythraeum, a major marine
      diazotroph. In addition, Silicibacter sp. TrichCH4B is the first characterized
      bacteria to harbor both the NOS and H-NOX proteins, making it uniquely capable of
      both synthesizing and sensing NO, analogous to mammalian NO signaling. Our study
      expands current understanding of the role of NO in bacterial signaling, providing
      a novel role for NO in bacterial communication and symbiosis.

PMID- 25944857
TI  - Target mechanism-based whole-cell screening identifies bortezomib as an inhibitor
      of caseinolytic protease in mycobacteria.
AB  - A novel type of antibacterial screening method, a target mechanism-based whole
      cell screening method, was developed to combine the advantages of target
      mechanism- and whole-cell-based approaches. A mycobacterial reporter strain with
      a synthetic phenotype for caseinolytic protease (ClpP1P2) activity was
      engineered, allowing the detection of inhibitors of this enzyme inside intact
      bacilli. A high-throughput screening method identified bortezomib, a human 26S
      proteasome drug, as a potent inhibitor of ClpP1P2 activity and bacterial growth.
      A battery of secondary assays was employed to demonstrate that bortezomib indeed
      exerts its antimicrobial activity via inhibition of ClpP1P2: Down- or
      upmodulation of the intracellular protease level resulted in hyper- or
      hyposensitivity of the bacteria, the drug showed specific potentiation of
      translation error-inducing aminoglycosides, ClpP1P2-specific substrate WhiB1
      accumulated upon exposure, and growth inhibition potencies of bortezomib
      derivatives correlated with ClpP1P2 inhibition potencies. Furthermore, molecular
      modeling showed that the drug can bind to the catalytic sites of ClpP1P2. This
      work demonstrates the feasibility of target mechanism-based whole-cell screening,
      provides chemical validation of ClpP1P2 as a target, and identifies a drug in
      clinical use as a new lead compound for tuberculosis therapy. IMPORTANCE: During
      the last decade, antibacterial drug discovery relied on biochemical assays,
      rather than whole-cell approaches, to identify molecules that interact with
      purified target proteins derived by genomics. This approach failed to deliver
      antibacterial compounds with whole-cell activity, either because of cell
      permeability issues that medicinal chemistry cannot easily fix or because genomic
      data of essentiality insufficiently predicted the vulnerability of the target
      identified. As a consequence, the field largely moved back to a whole-cell
      approach whose main limitation is its black-box nature, i.e., that it requires
      trial-and-error chemistry because the cellular target is unknown. We developed a
      novel type of antibacterial screening method, target mechanism-based whole-cell
      screening, to combine the advantages of both approaches. We engineered a
      mycobacterial reporter strain with a synthetic phenotype allowing us to identify
      inhibitors of the caseinolytic protease (ClpP1P2) inside the cell. This approach
      identified bortezomib, an anticancer drug, as a specific inhibitor of ClpP1P2. We
      further confirmed the specific "on-target" activity of bortezomib by independent
      approaches including, but not limited to, genetic manipulation of the target
      level (over- and underexpressing strains) and by establishing a dynamic structure
      activity relationship between ClpP1P2 and growth inhibition. Identifying an "on
      target" compound is critical to optimize the efficacy of the compound without
      compromising its specificity. This work demonstrates the feasibility of target
      mechanism-based whole-cell screening methods, validates ClpP1P2 as a druggable
      target, and delivers a lead compound for tuberculosis therapy.

PMID- 25944858
TI  - New players in the toxin field: polymorphic toxin systems in bacteria.
AB  - Bacteria have evolved numerous strategies to increase their competitiveness and
      fight against each other. Indeed, a large arsenal of antibacterial weapons is
      available in order to inhibit the proliferation of competitor cells. Polymorphic
      toxin systems (PTS), recently identified by bioinformatics in all major bacterial
      lineages, correspond to such a system primarily involved in conflict between
      related bacterial strains. They are typically composed of a secreted multidomain
      toxin, a protective immunity protein, and multiple cassettes encoding alternative
      toxic domains. The C-terminal domains of polymorphic toxins carry the toxic
      activity, whereas the N-terminal domains are related to the trafficking mode. In
      silico analysis of PTS identified over 150 distinct toxin domains, including
      putative nuclease, deaminase, or peptidase domains. Immunity genes found
      immediately downstream of the toxin genes encode small proteins that protect
      bacteria against their own toxins or against toxins secreted by neighboring
      cells. PTS encompass well-known colicins and pyocins, contact-dependent growth
      inhibition systems which include CdiA and Rhs toxins and some effectors of type
      VI secretion systems. We have recently characterized the MafB toxins, a new
      family of PTS deployed by pathogenic Neisseria spp. Many other putative PTS have
      been identified by in silico predictions but have yet to be characterized
      experimentally. However, the high number of these systems suggests that PTS have
      a fundamental role in bacterial biology that is likely to extend beyond
      interbacterial competition. 

PMID- 25944859
TI  - The Legionella Kinase LegK2 Targets the ARP2/3 Complex To Inhibit Actin
      Nucleation on Phagosomes and Allow Bacterial Evasion of the Late Endocytic
      Pathway.
AB  - Legionella pneumophila, the etiological agent of legionellosis, replicates within
      phagocytic cells. Crucial to biogenesis of the replicative vacuole is the Dot/Icm
      type 4 secretion system, which translocates a large number of effectors into the
      host cell cytosol. Among them is LegK2, a protein kinase that plays a key role in
      Legionella infection. Here, we identified the actin nucleator ARP2/3 complex as a
      target of LegK2. LegK2 phosphorylates the ARPC1B and ARP3 subunits of the ARP2/3
      complex. LegK2-dependent ARP2/3 phosphorylation triggers global actin
      cytoskeleton remodeling in cells, and it impairs actin tail formation by Listeria
      monocytogenes, a well-known ARP2/3-dependent process. During infection, LegK2 is
      addressed to the Legionella-containing vacuole surface and inhibits actin
      polymerization on the phagosome, as revealed by legK2 gene inactivation.
      Consequently, LegK2 prevents late endosome/lysosome association with the
      phagosome and finally contributes to remodeling of the bacterium-containing
      phagosome into a replicative niche. The inhibition of actin polymerization by
      LegK2 and its effect on endosome trafficking are ARP2/3 dependent since it can be
      phenocopied by a specific chemical inhibitor of the ARP2/3 complex. Thus, LegK2
      ARP2/3 interplay highlights an original mechanism of bacterial virulence with an
      unexpected role in local actin remodeling that allows bacteria to control vesicle
      trafficking in order to escape host defenses. IMPORTANCE: Deciphering the
      individual contribution of each Dot/Icm type 4 secretion system substrate to the
      intracellular life-style of L. pneumophila remains the principal challenge in
      understanding the molecular basis of Legionella virulence. Our finding that LegK2
      is a Dot/Icm effector that inhibits actin polymerization on the Legionella
      containing vacuole importantly contributes to the deciphering of the molecular
      mechanisms evolved by Legionella to counteract the endocytic pathway. Indeed, our
      results highlight the essential role of LegK2 in preventing late endosomes from
      fusing with the phagosome. More generally, this work is the first demonstration
      of local actin remodeling as a mechanism used by bacteria to control organelle
      trafficking. Further, by characterizing the role of the bacterial protein kinase
      LegK2, we reinforce the concept that posttranslational modifications are key
      strategies used by pathogens to evade host cell defenses.

PMID- 25944860
TI  - Genetic diversity in the collaborative cross model recapitulates human West Nile
      virus disease outcomes.
AB  - West Nile virus (WNV) is an emerging neuroinvasive flavivirus that now causes
      significant morbidity and mortality worldwide. The innate and adaptive immune
      responses to WNV infection have been well studied in C57BL/6J inbred mice, but
      this model lacks the variations in susceptibility, immunity, and outcome to WNV
      infection that are observed in humans, thus limiting its usefulness to understand
      the mechanisms of WNV infection and immunity dynamics. To build a model of WNV
      infection that captures human infection outcomes, we have used the Collaborative
      Cross (CC) mouse model. We show that this model, which recapitulates the genetic
      diversity of the human population, demonstrates diversity in susceptibility and
      outcomes of WNV infection observed in humans. Using multiple F1 crosses of CC
      mice, we identified a wide range of susceptibilities to infection, as
      demonstrated through differences in survival, clinical disease score, viral
      titer, and innate and adaptive immune responses in both peripheral tissues and
      the central nervous system. Additionally, we examined the Oas1b alleles in the CC
      mice and confirmed the previous finding that Oas1b plays a role in susceptibility
      to WNV; however, even within a given Oas1b allele status, we identified a wide
      range of strain-specific WNV-associated phenotypes. These results confirmed that
      the CC model is effective for identifying a repertoire of host genes involved in
      WNV resistance and susceptibility. The CC effectively models a wide range of WNV
      clinical, virologic, and immune phenotypes, thus overcoming the limitations of
      the traditional C57BL/6J model, allowing genetic and mechanistic studies of WNV
      infection and immunity in differently susceptible populations. IMPORTANCE: Mouse
      models of West Nile virus infection have revealed important details regarding the
      innate and adaptive immune responses to this emerging viral infection. However,
      traditional mouse models lack the genetic diversity present in human populations
      and therefore limit our ability to study various disease outcomes and immunologic
      mechanisms subsequent to West Nile virus infection. In this study, we used the
      Collaborative Cross mouse model to more effectively model the wide range of
      clinical, virologic, and immune phenotypes present upon West Nile virus infection
      in humans.

PMID- 25944861
TI  - Evidence for Posttranslational Protein Flavinylation in the Syphilis Spirochete
      Treponema pallidum: Structural and Biochemical Insights from the Catalytic Core
      of a Periplasmic Flavin-Trafficking Protein.
AB  - The syphilis spirochete Treponema pallidum is an important human pathogen but a
      highly enigmatic bacterium that cannot be cultivated in vitro. T. pallidum lacks
      many biosynthetic pathways and therefore has evolved the capability to exploit
      host-derived metabolites via its periplasmic lipoprotein repertoire. We recently
      reported a flavin-trafficking protein in T. pallidum (Ftp_Tp; TP0796) as the
      first bacterial metal-dependent flavin adenine dinucleotide (FAD) pyrophosphatase
      that hydrolyzes FAD into AMP and flavin mononucleotide (FMN) in the spirochete's
      periplasm. However, orthologs of Ftp_Tp from other bacteria appear to lack this
      hydrolytic activity; rather, they bind and flavinylate subunits of a cytoplasmic
      membrane redox system (Nqr/Rnf). To further explore this dichotomy, biochemical
      analyses, protein crystallography, and structure-based mutagenesis were used to
      show that a single amino acid change (N55Y) in Ftp_Tp converts it from an Mg(2+)
      dependent FAD pyrophosphatase to an FAD-binding protein. We also demonstrated
      that Ftp_Tp has a second enzymatic activity (Mg(2+)-FMN transferase); it
      flavinylates protein(s) covalently with FMN on a threonine side chain of an
      appropriate sequence motif using FAD as the substrate. Moreover, mutation of a
      metal-binding residue (D284A) eliminates Ftp_Tp's dual activities, thereby
      underscoring the role of Mg(2+) in the enzyme-catalyzed reactions. The
      posttranslational flavinylation activity that can target a periplasmic
      lipoprotein (TP0171) has not previously been described. The observed activities
      reveal the catalytic flexibility of a treponemal protein to perform multiple
      functions. Together, these findings imply mechanisms by which a dynamic pool of
      flavin cofactor is maintained and how flavoproteins are generated by Ftp_Tp
      locally in the T. pallidum periplasm. IMPORTANCE: Treponema pallidum, the
      syphilis spirochete, exploits its periplasmic lipoproteins for a number of
      essential physiologic processes. One of these, flavin-trafficking protein (Ftp),
      not only exploits its catalytic center to mediate posttranslational flavinylation
      of proteins (to create flavoproteins) but also likely maintains the periplasmic
      flavin pool via its unique ability to hydrolyze FAD. This functional diversity
      within a single lipoprotein is quite remarkable and reflects the enzymatic
      versatility of the treponemal lipoproteins, as well as molecular parsimony in an
      organism with a limited genome. Ftp-mediated protein flavinylation in the
      periplasm also likely is a key aspect of a predicted flavin-dependent Rnf-based
      redox homeostasis system at the cytoplasmic membrane of T. pallidum. In addition
      to its importance in T. pallidum physiology, Ftp homologs exist in other
      bacteria, thereby expanding our understanding of the bacterial periplasm as a
      metabolically active subcellular compartment for flavoprotein biogenesis as well
      as flavin homeostasis.

PMID- 25944862
TI  - Adenylate Charge Regulates Sensor Kinase CheS3 To Control Cyst Formation in
      Rhodospirillum centenum.
AB  - Rhodospirillum centenum forms metabolically dormant cysts under unfavorable
      growth conditions such as desiccation or nutrient starvation. The development of
      cysts is tightly regulated and involves a cyst-repressing chemotaxis-like signal
      transduction pathway called the Che3 signaling cascade. The Che3 cascade is
      comprised of a methyl chemoreceptor (MCP3), receptor-methylating/demethylating
      proteins CheB3 and CheR3, two CheW3 linker proteins, a CheA3-CheY hybrid
      histidine kinase, and a single-domain response regulator, CheY3. In addition to
      Che-like components, the Che3 cascade also contains a second hybrid histidine
      kinase, CheS3. Recent biochemical and genetic studies show that CheA3 does not
      serve as a phosphor donor for CheY3; instead, CheA3 inhibits a CheS3->CheY3 two
      component system by phosphorylating an inhibitory receiver domain of CheS3. In
      this study, we show that in addition to phosphorylation by CheA3, the
      phosphorylation state of CheS3 is also regulated by the cellular energy level as
      quantified by the molar ratio of ATP/(ATP + ADP). A 35% decrease in cellular
      energy is shown to occur in vivo upon a nutrient downshift that gives rise to
      cyst formation. When this energy decline is replicated in vitro, the
      phosphorylation level of CheS3 is reduced by ~75%. Finally, we also show that ADP
      mediated reduction of CheS3 phosphorylation is a consequence of ADP enhancing
      autodephosphorylation of CheS3. IMPORTANCE: Upon starvation, Rhodospirillum
      centenum undergoes a developmental process that forms metabolically dormant
      cysts, which withstand desiccation and nutritional limitation. This study
      explores the role of the cellular energy state as measured by the ratio of ATP to
      ADP as an important regulator of cyst formation in Rhodospirillum centenum. We
      show that R. centenum cells experience a significant reduction in ATP during cyst
      formation using ATP/(ATP + ADP) as a measurement. When this in vivo level of
      energy starvation is simulated in vitro, CheS3 phosphorylation is reduced by 75%.
      This profound reduction in CheS3 autophosphorylation is contrasted with a much
      lower 25% decrease in CheA3 phosphorylation in response to a similar downward
      shift in ATP/(ATP + ADP). We argue that even though adenylate energy affects all
      ATP-dependent enzymes to an extent, the enhanced inhibition of CheS3 activity in
      response to a reduction in the ATP/(ATP + ADP) ratio likely functions as an
      important input signal to regulate cyst development.

PMID- 25944864
TI  - Pondering Mating: Pneumocystis jirovecii, the Human Lung Pathogen, Selfs without
      Mating Type Switching, in Contrast to Its Close Relative Schizosaccharomyces
      pombe.

PMID- 25944870
TI  - Key features of an EU health information system: a concept mapping study.
AB  - BACKGROUND: Despite the acknowledged value of an EU health information system (EU
      HISys) and the many achievements in this field, the landscape is still heavily
      fragmented and incomplete. Through a systematic analysis of the opinions and
      valuations of public health stakeholders, this study aims to conceptualize key
      features of an EU-HISys. METHODS: Public health professionals and policymakers
      were invited to participate in a concept mapping procedure. First, participants
      (N = 34) formulated statements that reflected their vision of an EU-HISys.
      Second, participants (N = 28) rated the relative importance of each statement and
      grouped conceptually similar ones. Principal Component and cluster analyses were
      used to condense these results to EU-HISys key features in a concept map. The
      number of key features and the labelling of the concept map were determined by
      expert consensus. RESULTS: The concept map contains 10 key features that
      summarize 93 statements. The map consists of a horizontal axis that represents
      the relevance of an 'organizational strategy', which deals with the 'efforts' to
      design and develop an EU-HISys and the 'achievements' gained by a functioning EU
      HISys. The vertical axis represents the 'professional orientation' of the EU
      HISys, ranging from the 'scientific' through to the 'policy' perspective. The top
      ranking statement expressed the need to establish a system that is permanent and
      sustainable. The top ranking key feature focuses on data and information quality.
      CONCLUSIONS: This study provides insights into key features of an EU-HISys. The
      results can be used to guide future planning and to support the development of a
      health information system for Europe.

PMID- 25944869
TI  - Return to the ED and hospitalisation following minor injuries among older persons
      treated in the emergency department: predictors among independent seniors within
      6 months.
AB  - BACKGROUND: minor traumatic injuries among independent older people have received
      little attention to date, but increasingly the impact of such injuries is being
      recognised. OBJECTIVES: we assessed the frequency and predictors of acute health
      care use, defined as return to the emergency department (ED) or hospitalisation.
      STUDY DESIGN: national multicentre prospective observational study. SETTING:
      eight Canadian teaching EDs between April 2009 and April 2013. PARTICIPANTS: a
      total of 1,568 patients aged 65-100 years, independent in basic activities of
      daily living, discharged from ED following a minor traumatic injury. METHODS:
      trained assessors measured baseline data including demographics, functional
      status, cognition, comorbidities, frailty and injury severity. We then conducted
      follow-up telephone interviews at 6 months to assess subsequent acute health care
      use. We used log-binomial regression analyses to identify predictors of acute
      health care use, and reported relative risks and 95% CIs. RESULTS: participants'
      mean age was 77.0, 66.4% female, and their injuries included contusions (43.5%),
      lacerations (25.1%) and fractures (25.4%). The cumulative rate of acute health
      care use by 6 months post-injury was 21.5% (95% CI: 19.0-24.3%). The strongest
      predictors of acute health care use within 6 months were cognitive impairment, RR
      = 1.6 (95% IC: 1.2-2.1) and the mechanism of injury including pedestrian struck
      or recreational injuries, RR = 1.6 (95% CI 1.2-2.2). CONCLUSIONS: among
      independent community living older persons with a minor injury, cognitive
      impairment and mechanism of injury were independent risk factors for acute
      healthcare use. Future studies should look at whether tailored discharge planning
      can reduce the need for acute health care use.

PMID- 25944863
TI  - Eco-Evolutionary Dynamics of Episomes among Ecologically Cohesive Bacterial
      Populations.
AB  - Although plasmids and other episomes are recognized as key players in horizontal
      gene transfer among microbes, their diversity and dynamics among ecologically
      structured host populations in the wild remain poorly understood. Here, we show
      that natural populations of marine Vibrionaceae bacteria host large numbers of
      families of episomes, consisting of plasmids and a surprisingly high fraction of
      plasmid-like temperate phages. Episomes are unevenly distributed among host
      populations, and contrary to the notion that high-density communities in biofilms
      act as hot spots of gene transfer, we identified a strong bias for episomes to
      occur in free-living as opposed to particle-attached cells. Mapping of episomal
      families onto host phylogeny shows that, with the exception of all phage and a
      few plasmid families, most are of recent evolutionary origin and appear to have
      spread rapidly by horizontal transfer. Such high eco-evolutionary turnover is
      particularly surprising for plasmids that are, based on previously suggested
      categorization, putatively nontransmissible, indicating that this type of plasmid
      is indeed frequently transferred by currently unknown mechanisms. Finally,
      analysis of recent gene transfer among plasmids reveals a network of extensive
      exchange connecting nearly all episomes. Genes functioning in plasmid transfer
      and maintenance are frequently exchanged, suggesting that plasmids can be rapidly
      transformed from one category to another. The broad distribution of episomes
      among distantly related hosts and the observed promiscuous recombination patterns
      show how episomes can offer their hosts rapid assembly and dissemination of novel
      functions. IMPORTANCE: Plasmids and other episomes are an integral part of
      bacterial biology in all environments, yet their study is heavily biased toward
      their role as vectors for antibiotic resistance genes. This study presents a
      comprehensive analysis of all episomes within several coexisting bacterial
      populations of Vibrionaceae from the coastal ocean and represents the largest-yet
      genomic survey of episomes from a single bacterial family. The host population
      framework allows analysis of the eco-evolutionary dynamics at unprecedented
      resolution, yielding several unexpected results. These include (i) discovery of
      novel, nonintegrative temperate phages, (ii) revision of a class of episomes,
      previously termed "nontransmissible," as highly transmissible, and (iii)
      surprisingly high evolutionary turnover of episomes, manifest as frequent birth,
      spread, and loss.

PMID- 25944871
TI  - Re-evaluation of dioxygenase gene phylogeny for the development and validation of
      a quantitative assay for environmental aromatic hydrocarbon degraders.
AB  - Rieske non-heme iron oxygenases enzymes have been widely studied, as they
      catalyse essential reactions initiating the bacterial degradation of organic
      compounds, for instance aromatic hydrocarbons. The genes encoding these enzymes
      offer a potential target for studying aromatic hydrocarbon-degrading organisms in
      the environment. However, previously reported primer sets that target dioxygenase
      gene sequences or the common conserved Rieske centre of aromatics dioxygenases
      have limited specificity and/or target non-dioxygenase genes. In this work, an
      extensive database of dioxygenase alpha-subunit gene sequences was constructed,
      and primer sets targeting the conserved Rieske centre were developed. The high
      specificity of the primers was confirmed by polymerase chain reaction analysis,
      agarose gel electrophoresis and sequencing. Quantitative polymerase chain
      reaction (qPCR) assays were also developed and optimized, following MIQE
      guidelines (Minimum Information for Publication of Quantitative Real-Time PCR
      Experiments). Comparison of the qPCR quantification of dioxygenases in spiked
      sediment samples and in pure cultures demonstrated an underestimation of the Ct
      value, and the requirement for a correction factor at gene abundances below 10(8)
      gene copies per g of sediment. Externally validated qPCR provides a valuable tool
      to monitor aromatic hydrocarbon degrader population abundances at contaminated
      sites.

PMID- 25944874
TI  - Effect of Intensive Versus Standard Blood Glucose Control in Patients With Type 2
      Diabetes Mellitus in Different Regions of the World: Systematic Review and Meta
      analysis of Randomized Controlled Trials.
AB  - BACKGROUND: Regional variation in type 2 diabetes mellitus care may affect
      outcomes in patients treated with intensive versus standard blood glucose
      control. We sought to evaluate these differences between North America and the
      rest of the world. METHODS AND RESULTS: Databases were searched from their
      inception through December 2013. Randomized controlled trials comparing the
      effects of intensive therapy with standard therapy for macro- and microvascular
      complications in adults with type 2 diabetes mellitus were selected. We
      calculated summary odds ratios (ORs) and 95% CIs with the random-effects model.
      The analysis included 34 967 patients from 17 randomized controlled trials (7 in
      North America and 10 in the rest of the world). There were no significant
      differences between intensive and standard therapy groups for all-cause mortality
      (OR 1.03, 95% CI 0.93 to 1.13) and cardiovascular mortality (OR 1.09, 95% CI 0.90
      to 1.32). For trials conducted in North America, intensive therapy compared with
      standard glycemic control resulted in significantly higher all-cause mortality
      (OR 1.21, 95% CI 1.05 to 1.40) and cardiovascular mortality (OR 1.41, 95% CI 1.05
      to 1.90) than trials conducted in the rest of the world (all-cause mortality OR
      0.93, 95% CI 0.85 to 1.03; interaction P=0.006; cardiovascular mortality OR 0.89,
      95% CI, 0.79 to 1.00; interaction P=0.007). Analysis of individual macro- and
      microvascular outcomes revealed no significant regional differences; however, the
      risk of severe hypoglycemia was significantly higher in trials of intensive
      therapy in North America (OR 3.52, 95% CI 3.07 to 4.03) compared with the rest of
      the world (OR 1.45, 95% CI 0.85 to 2.47; interaction P=0.001). CONCLUSION:
      Randomization to intensive glycemic control in type 2 diabetes mellitus patients
      was associated with increases in all-cause mortality, cardiovascular mortality,
      and severe hypoglycemia in North America compared with the rest of the world.
      Further investigation into the pathobiology or patient variability underlying
      these findings is warranted.

PMID- 25944875
TI  - Pulmonary congestion at rest and abnormal ventilation during exercise in chronic
      systolic heart failure.
AB  - BACKGROUND: In patients with chronic heart failure, abnormal ventilation at
      cardiopulmonary testing (expressed by minute ventilation-to-carbon dioxide
      production, or VE/VCO2 slope, and resting end-tidal CO2 pressure) may derive
      either from abnormal autonomic or chemoreflex regulation or from lung dysfunction
      induced by pulmonary congestion. The latter hypothesis is supported by
      measurement of pulmonary capillary wedge pressure, which cannot be obtained
      routinely but may be estimated noninvasively by measuring transthoracic
      conductance (thoracic fluid content 1/kOmega) with impedance cardiography.
      METHODS AND RESULTS: Preliminarily, in 9 patients undergoing invasive
      hemodynamics during cardiopulmonary testing, we demonstrated a significant
      relationship between VE/VCO2 slope and resting end-tidal CO2 pressure with
      baseline and peak pulmonary capillary wedge pressure. Later, noninvasive
      hemodynamic evaluation by impedance cardiography was performed before
      cardiopulmonary testing in 190 patients with chronic systolic heart failure and
      normal lung function (aged 67+/-3 years, 71% with ischemia, ejection fraction
      32+/-7%, 69% with implantable cardioverter-defibrillator or cardiac
      resynchronization therapy). In this group, we determined the relationship between
      abnormal ventilation (VE/VCO2 slope and resting end-tidal CO2 pressure) and
      transthoracic conductance. In the whole population, thoracic fluid content values
      were significantly related to VE/VCO2 slope (R=0.63, P<0.0001) and to resting end
      tidal CO2 pressure (R=-0.44, P<0.001). CONCLUSIONS: In patients with chronic
      heart failure, abnormal ventilation during exercise may be related in part to
      pulmonary congestion, as detected by resting baseline impedance cardiography.

PMID- 25944876
TI  - Volume overload and adverse outcomes in chronic kidney disease: clinical
      observational and animal studies.
AB  - BACKGROUND: Volume overload is frequently encountered and is associated with
      cardiovascular risk factors in patients with chronic kidney disease (CKD).
      However, the relationship between volume overload and adverse outcomes in CKD is
      not fully understood. METHODS AND RESULTS: A prospective cohort of 338 patients
      with stage 3 to 5 CKD was followed for a median of 2.1 years. The study
      participants were stratified by the presence or absence of volume overload,
      defined as an overhydration index assessed by bioimpedance spectroscopy exceeding
      7%, the 90th percentile for the healthy population. The primary outcome was the
      composite of estimated glomerular filtration rate decline >=50% or end-stage
      renal disease. The secondary outcome included a composite of morbidity and
      mortality from cardiovascular causes. Animal models were used to simulate fluid
      retention observed in human CKD. We found that patients with volume overload were
      at a higher risk of the primary and secondary end points in the adjusted Cox
      models. Furthermore, overhydration appears to be more important than hypertension
      in predicting an elevated risk. In rats subjected to unilateral nephrectomy and a
      high-salt diet, the extracellular water significantly increased. This fluid
      retention was associated with an increase in blood pressure, proteinuria, renal
      inflammation with macrophage infiltration and tumor necrosis factor-alpha
      overexpression, glomerular sclerosis, and cardiac fibrosis. Diuretic treatment
      with indapamide attenuated these changes, suggesting that fluid retention might
      play a role in the development of adverse outcomes. CONCLUSIONS: Volume overload
      contributes to CKD progression and cardiovascular diseases. Further research is
      warranted to clarify whether the correction of volume overload would improve
      outcomes for CKD patients.

PMID- 25944878
TI  - Aortic Pulse Wave Velocity in Healthy Children and Adolescents: Reference Values
      for the Vicorder Device and Modifying Factors.
AB  - BACKGROUND: Aortic pulse wave velocity (PWV), an indicator of arterial stiffness,
      independently predicts cardiovascular mortality risk in adults. Arterial
      stiffening advances with age and seems accelerated in children with certain
      disease conditions such as chronic kidney disease or diabetes. The Vicorder, an
      oscillometric device to measure PWV, has been validated in children, but
      reference values in a large pediatric cohort, association to carotid stiffness
      and influence of individual and family risk factors have not been determined.
      METHODS: Pulse waves were captured in 1,003 healthy children (aged 6-18 years) in
      6 centers and gender-specific reference data normalized to age/height were
      constructed. In 589 children carotid distensibility and intima media thickness
      were measured. Gestational and family history was reported. RESULTS: PWV
      correlated with age (r = 0.57, P < 0.0001) with significant gender-related
      differences starting at age 9. Further significant correlations were seen for
      height, weight, body mass index, blood pressure, pulse pressure, and heart rate.
      Independent predictors for PWV in a multivariate regression analysis were gender,
      age, height, weight, mean arterial pressure, and heart rate. Risk factors for
      higher PWV included small for gestational age at birth, secondhand smoking,
      parental hypertension, and obesity. PWV showed weak correlations with 2 of the
      carotid distensibility measures, but not with intima media thickness. CONCLUSION:
      This study defines reference values for PWV captured by the Vicorder device in
      children and adolescents and reveals associations with potential cardiovascular
      risk factors in a healthy population. Gender-specific percentiles for age/height
      will allow for the assessment of pediatric cohorts using this oscillometric
      method.

PMID- 25944877
TI  - Cypher and Enigma homolog protein are essential for cardiac development and
      embryonic survival.
AB  - BACKGROUND: The striated muscle Z-line, a multiprotein complex at the boundary
      between sarcomeres, plays an integral role in maintaining striated muscle
      structure and function. Multiple Z-line-associated proteins have been identified
      and shown to play an increasingly important role in the pathogenesis of human
      cardiomyopathy. Cypher and its close homologue, Enigma homolog protein (ENH), are
      2 Z-line proteins previously shown to be individually essential for maintenance
      of postnatal cardiac function and stability of the Z-line during muscle
      contraction, but dispensable for cardiac myofibrillogenesis and development.
      METHODS AND RESULTS: The current studies were designed to test whether Cypher and
      ENH play redundant roles during embryonic development. Here, we demonstrated that
      mice lacking both ENH and Cypher exhibited embryonic lethality and growth
      retardation. Lethality in double knockout embryos was associated with cardiac
      dilation and abnormal Z-line structure. In addition, when ENH was ablated in
      conjunction with selective ablation of either Cypher short isoforms (CypherS), or
      Cypher long isoforms (CypherL), only the latter resulted in embryonic lethality.
      CONCLUSIONS: Cypher and ENH redundantly play an essential role in sustaining Z
      line structure from the earliest stages of cardiac function, and are redundantly
      required to maintain normal embryonic heart function and embryonic viability.

PMID- 25944879
TI  - Excessive secretion of IL-8 by skeletal muscle in type 2 diabetes impairs tube
      growth: potential role of PI3K and the Tie2 receptor.
AB  - Reduced capillary density is a feature of skeletal muscle (SkM) in type 2
      diabetes (T2D), which is associated with multiple metabolic and functional
      abnormalities. SkM has been identified as a secretory tissue, releasing myokines
      that regulate multiple processes, including vascularization. We sought to
      determine how myokines secreted from T2D myotubes might influence SkM
      angiogenesis. Conditioned media (CM) were generated by myotubes from T2D and
      nondiabetic (ND) subjects. Primary human endothelial cells (HUVEC) and SkM
      explants were exposed to CM or recombinant myokines, and tube number or capillary
      outgrowth was determined as well as measurement of protein expression and
      phosphorylation. CM from ND myotubes stimulated tube formation of HUVEC to a
      greater extent than T2D myotubes (T2D-CM = 100%, ND-CM = 288 +/- 90% after 48 h,
      P < 0.05). The effects of T2D myotube CM were mediated by IL-8, not IL-15 or
      GROalpha, and were due not to cell damage but rather through regulating tube
      production and maintenance (response to T2D-IL-8 = 100%, response to ND-IL-8 =
      263 +/- 46% after 48 h, P < 0.05). A similar effect was seen in SkM explants with
      exposure to IL-8. The dose-dependent effect of IL-8 on tube formation was also
      observable in the PI3K and FAK signaling pathways and mediated at least in part
      by PI3K, leading to regulation of Tie2 expression. These results suggest that
      elevated levels of IL-8 secreted from T2D myotubes create a muscle
      microenvironment that supports reduced capillarization in T2D. Impaired
      vascularization of SkM limits the availability of substrates, including glucose
      and contributes to the T2D phenotype.

PMID- 25944880
TI  - Palmitate-induced inflammatory pathways in human adipose microvascular
      endothelial cells promote monocyte adhesion and impair insulin transcytosis.
AB  - Obesity is associated with inflammation and immune cell recruitment to adipose
      tissue, muscle and intima of atherosclerotic blood vessels. Obesity and
      hyperlipidemia are also associated with tissue insulin resistance and can
      compromise insulin delivery to muscle. The muscle/fat microvascular endothelium
      mediates insulin delivery and facilitates monocyte transmigration, yet its
      contribution to the consequences of hyperlipidemia is poorly understood. Using
      primary endothelial cells from human adipose tissue microvasculature (HAMEC), we
      investigated the effects of physiological levels of fatty acids on endothelial
      inflammation and function. Expression of cytokines and adhesion molecules was
      measured by RT-qPCR. Signaling pathways were evaluated by pharmacological
      manipulation and immunoblotting. Surface expression of adhesion molecules was
      determined by immunohistochemistry. THP1 monocyte interaction with HAMEC was
      measured by cell adhesion and migration across transwells. Insulin transcytosis
      was measured by total internal reflection fluorescence microscopy. Palmitate, but
      not palmitoleate, elevated the expression of IL-6, IL-8, TLR2 (Toll-like receptor
      2), and intercellular adhesion molecule 1 (ICAM-1). HAMEC had markedly low fatty
      acid uptake and oxidation, and CD36 inhibition did not reverse the palmitate
      induced expression of adhesion molecules, suggesting that inflammation did not
      arise from palmitate uptake/metabolism. Instead, inhibition of TLR4 to NF-kappaB
      signaling blunted palmitate-induced ICAM-1 expression. Importantly, palmitate
      induced surface expression of ICAM-1 promoted monocyte binding and
      transmigration. Conversely, palmitate reduced insulin transcytosis, an effect
      reversed by TLR4 inhibition. In summary, palmitate activates inflammatory
      pathways in primary microvascular endothelial cells, impairing insulin transport
      and increasing monocyte transmigration. This behavior may contribute in vivo to
      reduced tissue insulin action and enhanced tissue infiltration by immune cells. 

PMID- 25944881
TI  - Mitochondrial transcription factor A regulation of mitochondrial degeneration in
      experimental diabetic neuropathy.
AB  - Oxidative stress-induced mitochondrial dysfunction and mitochondrial DNA (mtDNA)
      damage in peripheral neurons is considered to be important in the development of
      diabetic neuropathy. Mitochondrial transcription factor A (TFAM) wraps mtDNA and
      promotes mtDNA replication and transcription. We studied whether overexpression
      of TFAM reverses experimental peripheral diabetic neuropathy using TFAM
      transgenic mice (TFAM Tg) that express human TFAM (hTFAM). Levels of mouse mtDNA
      and the total TFAM (mouse TFAM + hTFAM) in the dorsal root ganglion (DRG)
      increased by approximately twofold in the TFAM Tg mice compared with control (WT)
      mice. WT and TFAM Tg mice were made diabetic by the administration of
      streptozotocin. Neuropathy end points were motor and sensory nerve conduction
      velocities, mechanical allodynia, thermal nociception, and intraepidermal nerve
      fiber density (IENFD). In the DRG neurons, mtDNA copy number and damage to mtDNA
      were quantified by qPCR, and TFAM levels were measured by Western blot. Mice with
      16-wk duration of diabetes developed motor and sensory nerve conduction deficits,
      behavioral deficits, and intraepidermal nerve fiber loss. All of these changes
      were mostly prevented in diabetic TFAM Tg mice and were independent of changes in
      blood parameters. Mice with 16 wk of diabetes had a 40% decrease in mtDNA copy
      number compared with nondiabetic mice (P < 0.01). Importantly, the mtDNA copy
      number in diabetic TFAM Tg mice reached the same level as that of WT nondiabetic
      mice. In comparison, there was upregulation of mtDNA and TFAM in 6-wk diabetic
      mice, suggesting that TFAM activation could be a therapeutic strategy to treat
      peripheral neuropathy. 

PMID- 25944884
TI  - Invited commentary: boundless science--putting natural direct and indirect
      effects in a clearer empirical context.
AB  - Epidemiologists are increasingly using natural effects for applied mediation
      analyses, yet 1 key identifying assumption is unintuitive and subject to some
      controversy. In this issue of the Journal, Jiang and VanderWeele (Am J Epidemiol.
      2015;182(2):105-108) formalize the conditions under which the difference method
      can be used to estimate natural indirect effects. In this commentary, I discuss
      implications of the controversial "cross-worlds" independence assumption needed
      to identify natural effects. I argue that with a binary mediator, a simple
      modification of the authors' approach will provide bounds for natural direct and
      indirect effect estimates that better reflect the capacity of the available data
      to support empirical statements on the presence of mediated effects. I discuss
      complications encountered when odds ratios are used to decompose effects, as well
      as the implications of incorrectly assuming the absence of exposure-induced
      mediator-outcome confounders. I note that the former problem can be entirely
      resolved using collapsible measures of effect, such as risk ratios. In the
      Appendix, I use previous derivations for natural direct effect bounds on the risk
      difference scale to provide bounds on the odds ratio scale that accommodate 1)
      uncertainty due to the cross-world independence assumption and 2) uncertainty due
      to the cross-world independence assumption and the presence of exposure-induced
      mediator-outcome confounders. 

PMID- 25944883
TI  - Novel Host Proteins and Signaling Pathways in Enteropathogenic E. coli
      Pathogenesis Identified by Global Phosphoproteome Analysis.
AB  - Enteropathogenic Escherichia coli (EPEC) uses a type III secretion system (T3SS)
      to directly translocate effector proteins into host cells where they play a
      pivotal role in subverting host cell signaling needed for disease. However, our
      knowledge of how EPEC affects host protein phosphorylation is limited to a few
      individual protein studies. We employed a quantitative proteomics approach to
      globally map alterations in the host phosphoproteome during EPEC infection. By
      characterizing host phosphorylation events at various time points throughout
      infection, we examined how EPEC dynamically impacts the host phosphoproteome over
      time. This experimental setup also enabled identification of T3SS-dependent and 
      independent changes in host phosphorylation. Specifically, T3SS-regulated events
      affected various cellular processes that are known EPEC targets, including
      cytoskeletal organization, immune signaling, and intracellular trafficking.
      However, the involvement of phosphorylation in these events has thus far been
      poorly studied. We confirmed the MAPK family as an established key host player,
      showed its central role in signal transduction during EPEC infection, and
      extended the repertoire of known signaling hubs with previously unrecognized
      proteins, including TPD52, CIN85, EPHA2, and HSP27. We identified altered
      phosphorylation of known EPEC targets, such as cofilin, where the involvement of
      phosphorylation has so far been undefined, thus providing novel mechanistic
      insights into the roles of these proteins in EPEC infection. An overlap of
      regulated proteins, especially those that are cytoskeleton-associated, was
      observed when compared with the phosphoproteome of Shigella-infected cells. We
      determined the biological relevance of the phosphorylation of a novel protein in
      EPEC pathogenesis, septin-9 (SEPT9). Both siRNA knockdown and a phosphorylation
      impaired SEPT9 mutant decreased bacterial adherence and EPEC-mediated cell death.
      In contrast, a phosphorylation-mimicking SEPT9 mutant rescued these effects.
      Collectively, this study provides the first global analysis of phosphorylation
      mediated processes during infection with an extracellular, diarrheagenic
      bacterial pathogen. 

PMID- 25944885
TI  - When is the difference method conservative for assessing mediation?
AB  - Assessment of indirect effects is useful for epidemiologists interested in
      understanding the mechanisms of exposure-outcome relationships. A traditional way
      of estimating indirect effects is to use the "difference method," which is based
      on regression analysis in which one adds a possible mediator to the regression
      model and examines whether the coefficient for the exposure changes. The
      difference method has been criticized for lacking a causal interpretation when it
      is used with logistic regression. In this article, we use the counterfactual
      framework to define the natural indirect effect (NIE) and assess the relationship
      between the NIE and the difference method. We show that under appropriate
      assumptions, the difference method consistently estimates the NIE for continuous
      outcomes and is always conservative for binary outcomes. Thus, the difference
      method can be used to provide evidence for the presence of mediation but not for
      the absence of mediation. 

PMID- 25944886
TI  - Jiang and VanderWeele respond to "bounding natural direct and indirect effects".

PMID- 25944887
TI  - Lactation in Relation to Long-Term Maternal Weight Gain in African-American
      Women.
AB  - We assessed the relationship of lactation to long-term maternal weight gain among
      African-American women, who have a lower prevalence of lactation and a higher
      prevalence of obesity than other US women. A pregnancy cohort of 3,147 African
      American women from the Black Women's Health Study who gave birth for the first
      time between 1995 and 2003 was followed for 8 years postpartum. Participants
      provided data on weight, lactation, gestational weight gain, education, diet, and
      exercise. Mean differences in weight gain were estimated in multivariable models.
      Overall, lactation was not associated with mean weight gain. However, the
      association was modified by prepregnancy body mass index (BMI; weight (kg)/height
      (m)2) (P for interaction=0.03): Among women with BMI<30 prior to the pregnancy,
      mean weight gain decreased with increasing months of lactation (P for
      trend<0.01), whereas among obese women (BMI>=30), mean weight gain increased with
      increasing duration of lactation (P for trend=0.04). Adjusted mean differences
      for >=12 months of lactation relative to no lactation were -1.56 kg (95%
      confidence interval: -2.50, -0.61) among nonobese women and 2.33 kg (95%
      confidence interval: -0.35, 5.01) among obese women. The differences in
      postpartum mean weight gain persisted over the 8-year study period. Residual
      confounding by factors more common in women who breastfeed longer may have
      influenced the results.

PMID- 25944888
TI  - Invited Commentary: Breastfeeding and Maternal Cardiovascular Health--Weighing
      the Evidence.
AB  - Recently, there has been growing interest in understanding the ways in which
      lactation affects maternal health. The accompanying article by Palmer et al. (Am
      J Epidemiol. 2015;181(12):932-939), particularly their finding that prepregnancy
      obesity modifies the relationship between lactation and postpartum weight gain,
      makes an important contribution to this field. In this commentary, I discuss
      these findings within the context of other recent literature which indicates that
      whether or not a mother breastfeeds her newborn appears to be a powerful
      predictor of the mother's future risk of developing diabetes, hypertension, and
      cardiovascular disease, independent of maternal weight or body mass index in
      later life. 

PMID- 25944889
TI  - Voices from the field: Expert reflections on mild cognitive impairment.

PMID- 25944893
TI  - Variation in Breast Cancer-Risk Factor Associations by Method of Detection:
      Results From a Series of Case-Control Studies.
AB  - Concerns about breast cancer overdiagnosis have increased the need to understand
      how cancers detected through screening mammography differ from those first
      detected by a woman or her clinician. We investigated risk factor associations
      for invasive breast cancer by method of detection within a series of case-control
      studies (1992-2007) carried out in Wisconsin, Massachusetts, and New Hampshire
      (n=15,648 invasive breast cancer patients and 17,602 controls aged 40-79 years).
      Approximately half of case women reported that their cancer had been detected by
      mammographic screening and half that they or their clinician had detected it. In
      polytomous logistic regression models, parity and age at first birth were more
      strongly associated with risk of mammography-detected breast cancer than with
      risk of woman/clinician-detected breast cancer (P<=0.01; adjusted for mammography
      utilization). Among postmenopausal women, estrogen-progestin hormone use was
      predominantly associated with risk of woman/clinician-detected breast cancer
      (odds ratio (OR)=1.49, 95% confidence interval (CI): 1.29, 1.72), whereas obesity
      was predominantly associated with risk of mammography-detected breast cancer
      (OR=1.72, 95% CI: 1.54, 1.92). Among regularly screened premenopausal women,
      obesity was not associated with increased risk of mammography-detected breast
      cancer (OR=0.99, 95% CI: 0.83, 1.18), but it was associated with reduced risk of
      woman/clinician-detected breast cancer (OR=0.53, 95% CI: 0.43, 0.64). These
      findings indicate important differences in breast cancer risk factors according
      to method of detection.

PMID- 25944894
TI  - 'In good conscience': conscience-based exemptions and proper medical treatment.
AB  - Lack of clarity about the proper limits of conscientious refusal to participate
      in particular healthcare practices has given rise to fears that, in the absence
      of clear parameters, conscience-based exemptions may become increasingly
      widespread, leading to intolerable burdens on health professionals, patients, and
      institutions. Here, we identify three factors which clarify the proper scope of
      conscience-based exemptions: the liminal zone of 'proper medical treatment' as
      their territorial extent; some criteria for genuine conscientiousness; and the
      fact that the exercise of a valid conscience-based exemption carries certain
      duties with it. These restricting factors should reassure those who worry that
      recognising rights of conscience at all inevitably risks rampant subjectivity and
      self-interest on the part of professionals. At the same time, they delineate a
      robust conscience zone: where a claim of conscience relates to treatment with
      liminal status and satisfies the criteria for conscientious character, as well as
      the conditions for conscientious performance, it deserves muscular legal
      protection. 

PMID- 25944895
TI  - Conscience and proper medical treatment.

PMID- 25944896
TI  - Mixing Pens and the Future of Diabetes Drugs.
AB  - With the availability of a smaller mixing pen, mass marketing of less stable
      medications is possible. Bidureon is one such medication, and the properties of
      its pen are discussed along with the prospects for future mixing pens. 

PMID- 25944897
TI  - Coordinated Regulation of Vasopressin Inactivation and Glucose Uptake by Action
      of TUG Protein in Muscle.
AB  - In adipose and muscle cells, insulin stimulates the exocytic translocation of
      vesicles containing GLUT4, a glucose transporter, and insulin-regulated
      aminopeptidase (IRAP), a transmembrane aminopeptidase. A substrate of IRAP is
      vasopressin, which controls water homeostasis. The physiological importance of
      IRAP translocation to inactivate vasopressin remains uncertain. We previously
      showed that in skeletal muscle, insulin stimulates proteolytic processing of the
      GLUT4 retention protein, TUG, to promote GLUT4 translocation and glucose uptake.
      Here we show that TUG proteolysis also controls IRAP targeting and regulates
      vasopressin action in vivo. Transgenic mice with constitutive TUG proteolysis in
      muscle consumed much more water than wild-type control mice. The transgenic mice
      lost more body weight during water restriction, and the abundance of renal AQP2
      water channels was reduced, implying that vasopressin activity is decreased. To
      compensate for accelerated vasopressin degradation, vasopressin secretion was
      increased, as assessed by the cosecreted protein copeptin. IRAP abundance was
      increased in T-tubule fractions of fasting transgenic mice, when compared with
      controls. Recombinant IRAP bound to TUG, and this interaction was mapped to a
      short peptide in IRAP that was previously shown to be critical for GLUT4
      intracellular retention. In cultured 3T3-L1 adipocytes, IRAP was present in TUG
      bound membranes and was released by insulin stimulation. Together with previous
      results, these data support a model in which TUG controls vesicle translocation
      by interacting with IRAP as well as GLUT4. Furthermore, the effect of IRAP to
      reduce vasopressin activity is a physiologically important consequence of vesicle
      translocation, which is coordinated with the stimulation of glucose uptake. 

PMID- 25944898
TI  - Forkhead Box O6 (FoxO6) Depletion Attenuates Hepatic Gluconeogenesis and Protects
      against Fat-induced Glucose Disorder in Mice.
AB  - Excessive endogenous glucose production contributes to fasting hyperglycemia in
      diabetes. FoxO6 is a distinct member of the FoxO subfamily. To elucidate the role
      of FoxO6 in hepatic gluconeogenesis and assess its contribution to the
      pathogenesis of fasting hyperglycemia in diabetes, we generated FoxO6 knock-out
      (FoxO6-KO) mice followed by determining the effect of FoxO6 loss-of-function on
      hepatic gluconeogenesis under physiological and pathological conditions. FoxO6
      depletion attenuated hepatic gluconeogenesis and lowered fasting glycemia in
      FoxO6-KO mice. FoxO6-deficient primary hepatocytes were associated with reduced
      capacities to produce glucose in response to glucagon. When fed a high fat diet,
      FoxO6-KO mice exhibited significantly enhanced glucose tolerance and reduced
      blood glucose levels accompanied by improved insulin sensitivity. These effects
      correlated with attenuated hepatic gluconeogenesis in FoxO6-KO mice. In contrast,
      wild-type littermates developed fat-induced glucose intolerance with a
      concomitant induction of fasting hyperinsulinemia and hyperglycemia. Furthermore,
      FoxO6-KO mice displayed significantly diminished macrophage infiltration into
      liver and adipose tissues, correlating with the reduction of macrophage
      expression of C-C chemokine receptor 2 (CCR2), a factor that is critical for
      regulating macrophage recruitment in peripheral tissues. Our data indicate that
      FoxO6 depletion protected against diet-induced glucose intolerance and insulin
      resistance by attenuating hepatic gluconeogenesis and curbing macrophage
      infiltration in liver and adipose tissues in mice. 

PMID- 25944899
TI  - The Tyrosine Kinase c-Abl Promotes Homeodomain-interacting Protein Kinase 2
      (HIPK2) Accumulation and Activation in Response to DNA Damage.
AB  - The non-receptor tyrosine kinase c-Abl is activated in response to DNA damage and
      induces p73-dependent apoptosis. Here, we investigated c-Abl regulation of the
      homeodomain-interacting protein kinase 2 (HIPK2), an important regulator of p53
      dependent apoptosis. c-Abl phosphorylated HIPK2 at several sites, and
      phosphorylation by c-Abl protected HIPK2 from degradation mediated by the
      ubiquitin E3 ligase Siah-1. c-Abl and HIPK2 synergized in activating p53 on
      apoptotic promoters in a reporter assay, and c-Abl was required for endogenous
      HIPK2 accumulation and phosphorylation of p53 at Ser(46) in response to DNA
      damage by gamma- and UV radiation. Accumulation of HIPK2 in nuclear speckles and
      association with promyelocytic leukemia protein (PML) in response to DNA damage
      were also dependent on c-Abl activity. At high cell density, the Hippo pathway
      inhibits DNA damage-induced c-Abl activation. Under this condition, DNA damage
      induced HIPK2 accumulation, phosphorylation of p53 at Ser(46), and apoptosis were
      attenuated. These data demonstrate a new mechanism for the induction of DNA
      damage-induced apoptosis by c-Abl and illustrate network interactions between
      serine/threonine and tyrosine kinases that dictate cell fate. 

PMID- 25944900
TI  - Mammalian Target of Rapamycin (mTOR) Tagging Promotes Dendritic Branch
      Variability through the Capture of Ca2+/Calmodulin-dependent Protein Kinase II
      alpha (CaMKIIalpha) mRNAs by the RNA-binding Protein HuD.
AB  - The fate of a memory, whether stored or forgotten, is determined by the ability
      of an active or tagged synapse to undergo changes in synaptic efficacy requiring
      protein synthesis of plasticity-related proteins. A synapse can be tagged, but
      without the "capture" of plasticity-related proteins, it will not undergo long
      lasting forms of plasticity (synaptic tagging and capture hypothesis). What the
      "tag" is and how plasticity-related proteins are captured at tagged synapses are
      unknown. Ca(2+)/calmodulin-dependent protein kinase II alpha (CaMKIIalpha) is
      critical in learning and memory and is synthesized locally in neuronal dendrites.
      The mechanistic (mammalian) target of rapamycin (mTOR) is a protein kinase that
      increases CaMKIIalpha protein expression; however, the mechanism and site of
      dendritic expression are unknown. Herein, we show that mTOR activity mediates the
      branch-specific expression of CaMKIIalpha, favoring one secondary, daughter
      branch over the other in a single neuron. mTOR inhibition decreased the dendritic
      levels of CaMKIIalpha protein and mRNA by shortening its poly(A) tail.
      Overexpression of the RNA-stabilizing protein HuD increased CaMKIIalpha protein
      levels and preserved its selective expression in one daughter branch over the
      other when mTOR was inhibited. Unexpectedly, deleting the third RNA recognition
      motif of HuD, the domain that binds the poly(A) tail, eliminated the branch
      specific expression of CaMKIIalpha when mTOR was active. These results provide a
      model for one molecular mechanism that may underlie the synaptic tagging and
      capture hypothesis where mTOR is the tag, preventing deadenylation of CaMKIIalpha
      mRNA, whereas HuD captures and promotes its expression in a branch-specific
      manner. 

PMID- 25944901
TI  - UDP-galactose (SLC35A2) and UDP-N-acetylglucosamine (SLC35A3) Transporters Form
      Glycosylation-related Complexes with Mannoside Acetylglucosaminyltransferases
      (Mgats).
AB  - UDP-galactose transporter (UGT; SLC35A2) and UDP-N-acetylglucosamine transporter
      (NGT; SLC35A3) form heterologous complexes in the Golgi membrane. NGT occurs in
      close proximity to mannosyl (alpha-1,6-)-glycoprotein beta-1,6-N
      acetylglucosaminyltransferase (Mgat5). In this study we analyzed whether NGT and
      both splice variants of UGT (UGT1 and UGT2) are able to interact with four
      different mannoside acetylglucosaminyltransferases (Mgat1, Mgat2, Mgat4B, and
      Mgat5). Using an in situ proximity ligation assay, we found that all examined
      glycosyltransferases are in the vicinity of these UDP-sugar transporters both at
      the endogenous level and upon overexpression. This observation was confirmed via
      the FLIM-FRET approach for both NGT and UGT1 complexes with Mgats. This study
      reports for the first time close proximity between endogenous nucleotide sugar
      transporters and glycosyltransferases. We also observed that among all analyzed
      Mgats, only Mgat4B occurs in close proximity to UGT2, whereas the other three
      Mgats are more distant from UGT2, and it was only possible to visualize their
      vicinity using proximity ligation assay. This strongly suggests that the distance
      between these protein pairs is longer than 10 nm but at the same time shorter
      than 40 nm. This study adds to the understanding of glycosylation, one of the
      most important post-translational modifications, which affects the majority of
      macromolecules. Our research shows that complex formation between nucleotide
      sugar transporters and glycosyltransferases might be a more common phenomenon
      than previously thought. 

PMID- 25944902
TI  - Novel Antibodies Reactive with Sialyl Lewis X in Both Humans and Mice Define Its
      Critical Role in Leukocyte Trafficking and Contact Hypersensitivity Responses.
AB  - Sialyl Lewis X (sLe(x)) antigen functions as a common carbohydrate determinant
      recognized by all three members of the selectin family. However, its expression
      and function in mice remain undefined due to the poor reactivity of conventional
      anti-sLe(x) monoclonal antibodies (mAbs) with mouse tissues. Here, we developed
      novel anti-sLe(x) mAbs, termed F1 and F2, which react well with both human and
      mouse sLe(x), by immunizing fucosyltransferase (FucT)-IV and FucT-VII doubly
      deficient mice with 6-sulfo-sLe(x)-expressing cells transiently transfected with
      an expression vector encoding CMP-N-acetylneuraminic acid hydroxylase. F1 and F2
      specifically bound both the N-acetyl and the N-glycolyl forms of sLe(x) as well
      as 6-sulfo-sLe(x), a major ligand for L-selectin expressed in high endothelial
      venules, and efficiently blocked physiological lymphocyte homing to lymph nodes
      in mice. Importantly, both of the mAbs inhibited contact hypersensitivity
      responses not only when administered in the L-selectin-dependent sensitization
      phase but also when administered in the elicitation phase in mice. When
      administered in the latter phase, F1 and F2 efficiently blocked rolling of mouse
      leukocytes along blood vessels expressing P- and E-selectin in the auricular skin
      in vivo. Consistent with these findings, the mAbs blocked P- and E-selectin
      dependent leukocyte rolling in a flow chamber assay. Taken together, these
      results indicate that novel anti-sLe(x) mAbs reactive with both human and mouse
      tissues, with the blocking ability against leukocyte trafficking mediated by all
      three selectins, have been established. These mAbs should be useful in
      determining the role of sLe(x) antigen under physiological and pathological
      conditions. 

PMID- 25944903
TI  - FBXO32 Targets c-Myc for Proteasomal Degradation and Inhibits c-Myc Activity.
AB  - FBXO32 (MAFbx/Atrogin-1) is an E3 ubiquitin ligase that is markedly up-regulated
      in muscle atrophy. Although some data indicate that FBXO32 may play an important
      role in tumorigenesis, the molecular mechanism of FBXO32 in tumorigenesis has
      been poorly understood. Here, we present evidence that FBXO32 targets the
      oncogenic protein c-Myc for ubiquitination and degradation through the proteasome
      pathway. Phosphorylation of c-Myc at Thr-58 and Ser-62 is dispensable for FBXO32
      to induce c-Myc degradation. Mutation of the lysine 326 in c-Myc reduces c-Myc
      ubiquitination and prevents the c-Myc degradation induced by FBXO32. Furthermore,
      overexpression of FBXO32 suppresses c-Myc activity and inhibits cell growth, but
      knockdown of FBXO32 enhances c-Myc activity and promotes cell growth. Finally, we
      show that FBXO32 is a direct downstream target of c-Myc, highlighting a negative
      feedback regulation loop between c-Myc and FBXO32. Thus, FBXO32 may function by
      targeting c-Myc. This work explains the function of FBXO32 and highlights its
      mechanisms in tumorigenesis. 

PMID- 25944904
TI  - Role of Dynamics in the Autoinhibition and Activation of the Hyperpolarization
      activated Cyclic Nucleotide-modulated (HCN) Ion Channels.
AB  - The hyperpolarization-activated cyclic nucleotide-modulated (HCN) ion channels
      control rhythmicity in neurons and cardiomyocytes. Cyclic AMP allosterically
      modulates HCN through the cAMP-dependent formation of a tetrameric gating ring
      spanning the intracellular region (IR) of HCN, to which cAMP binds. Although the
      apo versus holo conformational changes of the cAMP-binding domain (CBD) have been
      previously mapped, only limited information is currently available on the HCN IR
      dynamics, which have been hypothesized to play a critical role in the cAMP
      dependent gating of HCN. Here, using molecular dynamics simulations validated and
      complemented by experimental NMR and CD data, we comparatively analyze HCN IR
      dynamics in the four states of the thermodynamic cycle arising from the coupling
      between cAMP binding and tetramerization equilibria. This extensive set of
      molecular dynamics trajectories captures the active-to-inactive transition that
      had remained elusive for other CBDs, and it provides unprecedented insight on the
      role of IR dynamics in HCN autoinhibition and its release by cAMP. Specifically,
      the IR tetramerization domain becomes more flexible in the monomeric states,
      removing steric clashes that the apo-CDB structure would otherwise impose.
      Furthermore, the simulations reveal that the active/inactive structural
      transition for the apo-monomeric CBD occurs through a manifold of pathways that
      are more divergent than previously anticipated. Upon cAMP binding, these pathways
      become disallowed, pre-confining the CBD conformational ensemble to a tetramer
      compatible state. This conformational confinement primes the IR for
      tetramerization and thus provides a model of how cAMP controls HCN channel
      gating. 

PMID- 25944906
TI  - "Modifying" My Career toward Chromatin Biology.

PMID- 25944905
TI  - JIP3 Activates Kinesin-1 Motility to Promote Axon Elongation.
AB  - Kinesin-1 is a molecular motor responsible for cargo transport along microtubules
      and plays critical roles in polarized cells, such as neurons. Kinesin-1 can
      function as a dimer of two kinesin heavy chains (KHC), which harbor the motor
      domain, or as a tetramer in combination with two accessory light chains (KLC). To
      ensure proper cargo distribution, kinesin-1 activity is precisely regulated. Both
      KLC and KHC subunits bind cargoes or regulatory proteins to engage the motor for
      movement along microtubules. We previously showed that the scaffolding protein
      JIP3 interacts directly with KHC in addition to its interaction with KLC and
      positively regulates dimeric KHC motility. Here we determined the stoichiometry
      of JIP3-KHC complexes and observed approximately four JIP3 molecules binding per
      KHC dimer. We then determined whether JIP3 activates tetrameric kinesin-1
      motility. Using an in vitro motility assay, we show that JIP3 binding to KLC
      engages kinesin-1 with microtubules and that JIP3 binding to KHC promotes kinesin
      1 motility along microtubules. We tested the in vivo relevance of these findings
      using axon elongation as a model for kinesin-1-dependent cellular function. We
      demonstrate that JIP3 binding to KHC, but not KLC, is essential for axon
      elongation in hippocampal neurons as well as axon regeneration in sensory
      neurons. These findings reveal that JIP3 regulation of kinesin-1 motility is
      critical for axon elongation and regeneration. 

PMID- 25944907
TI  - Functional Architecture of the Cytoplasmic Entrance to the Cystic Fibrosis
      Transmembrane Conductance Regulator Chloride Channel Pore.
AB  - As an ion channel, the cystic fibrosis transmembrane conductance regulator must
      form a continuous pathway for the movement of Cl(-) and other anions between the
      cytoplasm and the extracellular solution. Both the structure and the function of
      the membrane-spanning part of this pathway are well defined. In contrast, the
      structure of the pathway that connects the cytoplasm to the membrane-spanning
      regions is unknown, and functional roles for different parts of the protein
      forming this pathway have not been described. We used patch clamp recording and
      substituted cysteine accessibility mutagenesis to identify positively charged
      amino acid side chains that attract cytoplasmic Cl(-) ions to the inner mouth of
      the pore. Our results indicate that the side chains of Lys-190, Arg-248, Arg-303,
      Lys-370, Lys-1041, and Arg-1048, located in different intracellular loops of the
      protein, play important roles in the electrostatic attraction of Cl(-) ions.
      Mutation and covalent modification of these residues have charge-dependent
      effects on the rate of Cl(-) permeation, demonstrating their functional role in
      maximization of Cl(-) flux. Other nearby positively charged side chains were not
      involved in electrostatic interactions with Cl(-). The location of these Cl(-)
      attractive residues suggests that cytoplasmic Cl(-) ions enter the pore via a
      lateral portal located between the cytoplasmic extensions to the fourth and sixth
      transmembrane helices; a secondary, functionally less relevant portal might exist
      between the extensions to the 10th and 12th transmembrane helices. These results
      define the cytoplasmic mouth of the pore and show how it attracts Cl(-) ions from
      the cytoplasm. 

PMID- 25944908
TI  - Kv Channel S1-S2 Linker Working as a Binding Site of Human beta-Defensin 2 for
      Channel Activation Modulation.
AB  - Among the three extracellular domains of the tetrameric voltage-gated K(+) (Kv)
      channels consisting of six membrane-spanning helical segments named S1-S6, the
      functional role of the S1-S2 linker still remains unclear because of the lack of
      a peptide ligand. In this study, the Kv1.3 channel S1-S2 linker was reported as a
      novel receptor site for human beta-defensin 2 (hBD2). hBD2 shifts the conductance
      voltage relationship curve of the human Kv1.3 channel in a positive direction by
      nearly 10.5 mV and increases the activation time constant for the channel. Unlike
      classical gating modifiers of toxin peptides from animal venoms, which generally
      bind to the Kv channel S3-S4 linker, hBD2 only targets residues in both the N and
      C termini of the S1-S2 linker to influence channel gating and inhibit channel
      currents. The increment and decrement of the basic residue number in a positively
      charged S4 sensor of Kv1.3 channel yields conductance-voltage relationship curves
      in the positive direction by ~31.2 mV and 2-4 mV, which suggests that positively
      charged hBD2 is anchored in the channel S1-S2 linker and is modulating channel
      activation through electrostatic repulsion with an adjacent S4 helix. Together,
      these findings reveal a novel peptide ligand that binds with the Kv channel S1-S2
      linker to modulate channel activation. These findings also highlight the
      functional importance of the Kv channel S1-S2 linker in ligand recognition and
      modification of channel activation. 

PMID- 25944909
TI  - Astrocyte Elevated Gene-1 (AEG-1) Contributes to Non-thyroidal Illness Syndrome
      (NTIS) Associated with Hepatocellular Carcinoma (HCC).
AB  - Non-thyroidal illness syndrome (NTIS), characterized by low serum 3,5,3'
      triiodothyronine (T3) with normal l-thyroxine (T4) levels, is associated with
      malignancy. Decreased activity of type I 5'-deiodinase (DIO1), which converts T4
      to T3, contributes to NTIS. T3 binds to thyroid hormone receptor, which
      heterodimerizes with retinoid X receptor (RXR) and regulates transcription of
      target genes, such as DIO1. NF-kappaB activation by inflammatory cytokines
      inhibits DIO1 expression. The oncogene astrocyte elevated gene-1 (AEG-1) inhibits
      RXR-dependent transcription and activates NF-kappaB. Here, we interrogated the
      role of AEG-1 in NTIS in the context of hepatocellular carcinoma (HCC). T3
      mediated gene regulation was analyzed in human HCC cells, with overexpression or
      knockdown of AEG-1, and primary hepatocytes from AEG-1 transgenic (Alb/AEG-1) and
      AEG-1 knock-out (AEG-1KO) mice. Serum T3 and T4 levels were checked in Alb/AEG-1
      mice and human HCC patients. AEG-1 and DIO1 levels in human HCC samples were
      analyzed by immunohistochemistry. AEG-1 inhibited T3-mediated gene regulation in
      human HCC cells and mouse hepatocytes. AEG-1 overexpression repressed and AEG-1
      knockdown induced DIO1 expression. An inverse correlation was observed between
      AEG-1 and DIO1 levels in human HCC patients. Low T3 with normal T4 was observed
      in the sera of HCC patients and Alb/AEG-1 mice. Inhibition of co-activator
      recruitment to RXR and activation of NF-kappaB were identified to play a role in
      AEG-1-mediated down-regulation of DIO1. AEG-1 thus might play a role in NTIS
      associated with HCC and other cancers. 

PMID- 25944910
TI  - Actinin-4 Governs Dendritic Spine Dynamics and Promotes Their Remodeling by
      Metabotropic Glutamate Receptors.
AB  - Dendritic spines are dynamic, actin-rich protrusions in neurons that undergo
      remodeling during neuronal development and activity-dependent plasticity within
      the central nervous system. Although group 1 metabotropic glutamate receptors
      (mGluRs) are critical for spine remodeling under physiopathological conditions,
      the molecular components linking receptor activity to structural plasticity
      remain unknown. Here we identify a Ca(2+)-sensitive actin-binding protein, alpha
      actinin-4, as a novel group 1 mGluR-interacting partner that orchestrates spine
      dynamics and morphogenesis in primary neurons. Functional silencing of alpha
      actinin-4 abolished spine elongation and turnover stimulated by group 1 mGluRs
      despite intact surface receptor expression and downstream ERK1/2 signaling. This
      function of alpha-actinin-4 in spine dynamics was underscored by gain-of-function
      phenotypes in untreated neurons. Here alpha-actinin-4 induced spine head
      enlargement, a morphological change requiring the C-terminal domain of alpha
      actinin-4 that binds to CaMKII, an interaction we showed to be regulated by group
      1 mGluR activation. Our data provide mechanistic insights into spine remodeling
      by metabotropic signaling and identify alpha-actinin-4 as a critical effector of
      structural plasticity within neurons. 

PMID- 25944912
TI  - 'A necessary evil that does not "really" cure disease': The domestication of
      biomedicine by Dutch holistic general practitioners.
AB  - Against the background of studies about the domestication of complementary and
      alternative medicine into biomedical settings, this article studies how
      biomedicine is integrated into holistic settings. Data from 19 in-depth
      interviews with Dutch holistic general practitioners who combine complementary
      and alternative medicine with conventional treatments demonstrate that they do
      not believe that conventional biomedicine 'really' cures patients. They feel that
      it merely suppresses the physical symptoms of a disease, leaving the more
      fundamental and non-physical causes intact. As a consequence, they use
      conventional biomedicine for strictly practical and instrumental reasons. This is
      the case in life-threatening or acute situations, understood as non-physical
      causes of disease having been left untreated with complementary and alternative
      medicine for too long. More mundane reasons for its use are the need to take
      patients' demands for biomedical treatment seriously or to obey authoritative
      rules, regulations and protocols. The integration of biomedicine into
      complementary and alternative medicine, then, follows the same logic of
      domestication of complementary and alternative medicine into biomedicine: it is
      made subordinate to the prevailing model of health and illness and treated as a
      practical add-on that does not 'really' cure people.

PMID- 25944911
TI  - Protein Depalmitoylation Is Induced by Wnt5a and Promotes Polarized Cell
      Behavior.
AB  - Wnt5a signaling regulates polarized cell behavior, but the downstream signaling
      events that promote cell polarity are not well understood. Our results show that
      Wnt5a promotes depalmitoylation of the melanoma cell adhesion molecule (MCAM) at
      cysteine 590. Mutation of Cys-590 to glycine is sufficient to polarize MCAM
      localization, similar to what is observed with Wnt5a stimulation. Inhibition of
      the depalmitoylating enzyme APT1 blocks Wnt5a-induced depalmitoylation,
      asymmetric MCAM localization, and cell invasion. Directly altering expression of
      the basal protein palmitoylation machinery is sufficient to promote cell
      invasion. Additionally, cancer mutations in palmitoyltransferases decrease MCAM
      palmitoylation and have impaired ability to suppress cell invasion. Our results
      provide evidence that Wnt5a induces protein depalmitoylation, which promotes
      polarized protein localization and cell invasion. 

PMID- 25944913
TI  - Inhibition of Nicotinamide Phosphoribosyltransferase (NAMPT), an Enzyme Essential
      for NAD+ Biosynthesis, Leads to Altered Carbohydrate Metabolism in Cancer Cells.
AB  - Nicotinamide phosphoribosyltransferase (NAMPT) has been extensively studied due
      to its essential role in NAD(+) biosynthesis in cancer cells and the prospect of
      developing novel therapeutics. To understand how NAMPT regulates cellular
      metabolism, we have shown that the treatment with FK866, a specific NAMPT
      inhibitor, leads to attenuation of glycolysis by blocking the glyceraldehyde 3
      phosphate dehydrogenase step (Tan, B., Young, D. A., Lu, Z. H., Wang, T., Meier,
      T. I., Shepard, R. L., Roth, K., Zhai, Y., Huss, K., Kuo, M. S., Gillig, J.,
      Parthasarathy, S., Burkholder, T. P., Smith, M. C., Geeganage, S., and Zhao, G.
      (2013) Pharmacological inhibition of nicotinamide phosphoribosyltransferase
      (NAMPT), an enzyme essential for NAD(+) biosynthesis, in human cancer cells:
      metabolic basis and potential clinical implications. J. Biol. Chem. 288, 3500
      3511). Due to technical limitations, we failed to separate isotopomers of
      phosphorylated sugars. In this study, we developed an enabling LC-MS methodology.
      Using this, we confirmed the previous findings and also showed that NAMPT
      inhibition led to accumulation of fructose 1-phosphate and sedoheptulose 1
      phosphate but not glucose 6-phosphate, fructose 6-phosphate, and sedoheptulose 7
      phosphate as previously thought. To investigate the metabolic basis of the
      metabolite formation, we carried out biochemical and cellular studies and
      established the following. First, glucose-labeling studies indicated that
      fructose 1-phosphate was derived from dihydroxyacetone phosphate and
      glyceraldehyde, and sedoheptulose 1-phosphate was derived from dihydroxyacetone
      phosphate and erythrose via an aldolase reaction. Second, biochemical studies
      showed that aldolase indeed catalyzed these reactions. Third, glyceraldehyde- and
      erythrose-labeling studies showed increased incorporation of corresponding labels
      into fructose 1-phosphate and sedoheptulose 1-phosphate in FK866-treated cells.
      Fourth, NAMPT inhibition led to increased glyceraldehyde and erythrose levels in
      the cell. Finally, glucose-labeling studies showed accumulated fructose 1,6
      bisphosphate in FK866-treated cells mainly derived from dihydroxyacetone
      phosphate and glyceraldehyde 3-phosphate. Taken together, this study shows that
      NAMPT inhibition leads to attenuation of glycolysis, resulting in further
      perturbation of carbohydrate metabolism in cancer cells. The potential clinical
      implications of these findings are also discussed. 

PMID- 25944914
TI  - Definitive and Adjuvant Radiotherapy in Locally Advanced Non-Small-Cell Lung
      Cancer: American Society of Clinical Oncology Clinical Practice Guideline
      Endorsement of the American Society for Radiation Oncology Evidence-Based
      Clinical Practice Guideline.
AB  - PURPOSE: The American Society for Radiation Oncology (ASTRO) produced an evidence
      based guideline on external-beam radiotherapy for patients with locally advanced
      non-small-cell lung cancer (NSCLC). Because of its relevance to the American
      Society of Clinical Oncology (ASCO) membership, ASCO endorsed the guideline after
      applying a set of procedures and a policy that are used to critically examine and
      endorse guidelines developed by other guideline development organizations.
      METHODS: The ASTRO guideline was reviewed by ASCO content experts for clinical
      accuracy and by ASCO methodologists for developmental rigor. On favorable review,
      an ASCO expert panel was convened and endorsed the guideline. The ASCO guideline
      approval body, the Clinical Practice Guideline Committee, approved the final
      endorsement. RESULTS: The recommendations from the ASTRO guideline, published in
      Practical Radiation Oncology, are clear, thorough, and based on the most relevant
      scientific evidence. The ASCO Endorsement Panel endorsed the guideline and added
      qualifying statements. RECOMMENDATIONS: For curative-intent treatment of locally
      advanced NSCLC, concurrent chemoradiotherapy improves local control and overall
      survival compared with sequential chemotherapy followed by radiation. The
      standard dose-fractionation of radiation is 60 Gy given in 2-Gy once-daily
      fractions over 6 weeks. There is no role for the routine use of induction therapy
      before chemoradiotherapy. Current data fail to support a clear role for
      consolidation therapy after chemoradiotherapy; however, consolidation therapy
      remains an option for patients who did not receive full systemic chemotherapy
      doses during radiotherapy. Important questions remain about the ideal concurrent
      chemotherapy regimen and optimal management of patients with resectable stage III
      disease.

PMID- 25944915
TI  - Identification of Lineage-Specific Cis-Regulatory Modules Associated with
      Variation in Transcription Factor Binding and Chromatin Activity Using Ornstein
      Uhlenbeck Models.
AB  - Scoring the impact of noncoding variation on the function of cis-regulatory
      regions, on their chromatin state, and on the qualitative and quantitative
      expression levels of target genes is a fundamental problem in evolutionary
      genomics. A particular challenge is how to model the divergence of quantitative
      traits and to identify relationships between the changes across the different
      levels of the genome, the chromatin activity landscape, and the transcriptome.
      Here, we examine the use of the Ornstein-Uhlenbeck (OU) model to infer selection
      at the level of predicted cis-regulatory modules (CRMs), and link these with
      changes in transcription factor binding and chromatin activity. Using publicly
      available cross-species ChIP-Seq and STARR-Seq data we show how OU can be applied
      genome-wide to identify candidate transcription factors for which binding site
      and CRM turnover is correlated with changes in regulatory activity. Next, we
      profile open chromatin in the developing eye across three Drosophila species. We
      identify the recognition motifs of the chromatin remodelers, Trithorax-like and
      Grainyhead as mostly correlating with species-specific changes in open chromatin.
      In conclusion, we show in this study that CRM scores can be used as quantitative
      traits and that motif discovery approaches can be extended towards more complex
      models of divergence. 

PMID- 25944916
TI  - Covariation Is a Poor Measure of Molecular Coevolution.
AB  - Recent developments in the analysis of amino acid covariation are leading to
      breakthroughs in protein structure prediction, protein design, and prediction of
      the interactome. It is assumed that observed patterns of covariation are caused
      by molecular coevolution, where substitutions at one site affect the evolutionary
      forces acting at neighboring sites. Our theoretical and empirical results cast
      doubt on this assumption. We demonstrate that the strongest coevolutionary signal
      is a decrease in evolutionary rate and that unfeasibly long times are required to
      produce coordinated substitutions. We find that covarying substitutions are
      mostly found on different branches of the phylogenetic tree, indicating that they
      are independent events that may or may not be attributable to coevolution. These
      observations undermine the hypothesis that molecular coevolution is the primary
      cause of the covariation signal. In contrast, we find that the pairs of residues
      with the strongest covariation signal tend to have low evolutionary rates, and
      that it is this low rate that gives rise to the covariation signal. Slowly
      evolving residue pairs are disproportionately located in the protein's core,
      which explains covariation methods' ability to detect pairs of residues that are
      close in three dimensions. These observations lead us to propose the "coevolution
      paradox": The strength of coevolution required to cause coordinated changes means
      the evolutionary rate is so low that such changes are highly unlikely to occur.
      As modern covariation methods may lead to breakthroughs in structural genomics,
      it is critical to recognize their biases and limitations. 

PMID- 25944917
TI  - EphB1 Suppression in Acute Myelogenous Leukemia: Regulating the DNA Damage
      Control System.
AB  - Loss of ephrin receptor (EphB1) expression may associate with aggressive cancer
      phenotypes; however, the mechanism of action remains unclear. To gain detailed
      insight into EphB1 function in acute myelogenous leukemia (AML), comprehensive
      analysis of EphB1 transcriptional regulation was conducted. In AML cells, EphB1
      transcript was inversely correlated with EphB1 promoter methylation. The presence
      of EphB1 allowed EfnB1 ligand-mediated p53 DNA binding, leading to restoration of
      the DNA damage response (DDR) cascade by the activation of ATR, Chk1, p53, p21,
      p38, CDK1(tyr15), and Bax, and downregulation of HSP27 and Bcl2. Comparatively,
      reintroduction of EphB1 expression in EphB1-methylated AML cells enhanced the
      same cascade of ATR, Chk1, p21, and CDK1(tyr15), which consequently enforced
      programmed cell death. Interestingly, in pediatric AML samples, EphB1 peptide
      phosphorylation and mRNA expression were actively suppressed as compared with
      normal bone marrow, and a significant percentage of the primary AML specimens had
      EphB1 promoter hypermethylation. Finally, EphB1 repression associated with a poor
      overall survival in pediatric AML. Combined, the contribution of EphB1 to the DDR
      system reveals a tumor-suppressor function for EphB1 in pediatric AML.
      IMPLICATIONS: The tumor-suppressor function of EphB1 is clinically relevant
      across many malignancies, suggesting that EphB1 is an important regulator of
      common cancer cell transforming pathways.

PMID- 25944919
TI  - Interruption to cutaneous gas exchange is not a likely mechanism of WNS
      associated death in bats.
AB  - Pseudogymnoascus destructans is the causative fungal agent of white-nose syndrome
      (WNS), an emerging fungal-borne epizootic. WNS is responsible for a catastrophic
      decline of hibernating bats in North America, yet we have limited understanding
      of the physiological interactions between pathogen and host. Pseudogymnoascus
      destructans severely damages wings and tail membranes, by causing dryness that
      leads to whole sections crumbling off. Four possible mechanisms have been
      proposed by which infection could lead to dehydration; in this study, we tested
      one: P. destructans infection could cause disruption to passive gas-exchange
      pathways across the wing membranes, thereby causing a compensatory increase in
      water-intensive pulmonary respiration. We hypothesized that total evaporative
      water loss would be greater when passive gas exchange was inhibited. We found
      that bats did not lose more water when passive pathways were blocked. This study
      provides evidence against the proposed proximal mechanism that disruption to
      passive gas exchange causes dehydration and death to WNS-infected bats. 

PMID- 25944918
TI  - Preclinical Evaluation of a Novel RXR Agonist for the Treatment of Neuroblastoma.
AB  - Neuroblastoma remains a common cause of pediatric cancer deaths, especially for
      children who present with advanced stage or recurrent disease. Currently,
      retinoic acid therapy is used as maintenance treatment to induce differentiation
      and reduce tumor recurrence following induction therapy for neuroblastoma, but
      unavoidable side effects are seen. A novel retinoid, UAB30, has been shown to
      generate negligible toxicities. In the current study, we hypothesized that UAB30
      would have a significant impact on multiple neuroblastoma cell lines in vitro and
      in vivo. Cellular survival, cell-cycle analysis, migration, and invasion were
      studied using AlamarBlue assays, FACS, and Transwell assays, respectively, in
      multiple cell lines following treatment with UAB30. In addition, an in vivo
      murine model of human neuroblastoma was utilized to study the effects of UAB30
      upon tumor xenograft growth and animal survival. We successfully demonstrated
      decreased cellular survival, invasion, and migration, cell-cycle arrest, and
      increased apoptosis after treatment with UAB30. Furthermore, inhibition of tumor
      growth and increased survival was observed in a murine neuroblastoma xenograft
      model. The results of these in vitro and in vivo studies suggest a potential
      therapeutic role for the low toxicity synthetic retinoid X receptor selective
      agonist, UAB30, in neuroblastoma treatment.

PMID- 25944920
TI  - Fluid absorption in the isolated midgut of adult female yellow fever mosquitoes
      (Aedes aegypti).
AB  - The transepithelial voltage (Vte) and the volume of isolated posterior midguts of
      adult female yellow fever mosquitoes (Aedes aegypti) were monitored. In all
      experiments, the initial Vte after filling the midgut was lumen negative, but
      subsequently became lumen positive at a rate of approximately 1 mV min(-1).
      Simultaneously, the midgut volume decreased, indicating spontaneous fluid
      absorption. When the midguts were filled and bathed with mosquito saline, the
      average rate of fluid absorption was 36.5+/-3.0 nl min(-1) (N=4, +/-s.e.m.). In
      the presence of theophylline (10 mmol l(-1)), Vte reached significantly higher
      lumen-positive values, but the rate of fluid absorption was not affected (N=6).
      In the presence of NaCN (5 mmol l(-1)), Vte remained close to 0 mV (N=4) and
      fluid absorption was reduced (14.4+/-1.3 nl min(-1), N=3, +/-s.e.m.). When
      midguts were filled with buffered NaCl (154 mmol l(-1) plus 1 mmol l(-1) HEPES)
      and bathed in mosquito saline with theophylline, fluid absorption was augmented
      (50.0+/-5.8 nl min(-1), N=12, +/-s.e.m.). Concanamycin A (10 umol l(-1)), ouabain
      (1 mmol l(-1)), and acetazolamide (1 mmol l(-1)) affected Vte in different ways,
      but all reduced fluid absorption by 60-70% of the value before addition of the
      drugs. 

PMID- 25944921
TI  - Aquatic surface respiration and swimming behaviour in adult and developing
      zebrafish exposed to hypoxia.
AB  - Severe hypoxia elicits aquatic surface respiration (ASR) behaviour in many
      species of fish, where ventilation of the gills at the air-water interface
      improves O2 uptake and survival. ASR is an important adaptation that may have
      given rise to air breathing in vertebrates. The neural substrate of this
      behaviour, however, is not defined. We characterized ASR in developing and adult
      zebrafish (Danio rerio) to ascertain a potential role for peripheral
      chemoreceptors in initiation or modulation of this response. Adult zebrafish
      exposed to acute, progressive hypoxia (PO2 from 158 to 15 mmHg) performed ASR
      with a threshold of 30 mmHg, and spent more time at the surface as PO2 decreased.
      Acclimation to hypoxia attenuated ASR responses. In larvae, ASR behaviour was
      observed between 5 and 21 days postfertilization with a threshold of 16 mmHg.
      Zebrafish decreased swimming behaviour (i.e. distance, velocity and acceleration)
      as PO2 was decreased, with a secondary increase in behaviour near or below
      threshold PO2 . In adults that underwent a 10-day intraperitoneal injection
      regime of 10 MUg g(-1) serotonin (5-HT) or 20 MUg g(-1) acetylcholine (ACh), an
      acute bout of hypoxia (15 mmHg) increased the time engaged in ASR by 5.5 and 4.9
      times, respectively, compared with controls. Larvae previously immersed in 10
      MUmol l(-1) 5-HT or ACh also displayed an increased ASR response. Our results
      support the notion that ASR is a behavioural response that is reliant upon input
      from peripheral O2 chemoreceptors. We discuss implications for the role of
      chemoreceptors in the evolution of air breathing.

PMID- 25944922
TI  - Hearing ability decreases in ageing locusts.
AB  - Insects display signs of ageing, despite their short lifespan. However, the
      limited studies on senescence emphasize longevity or reproduction. We focused on
      the hearing ability of ageing adult locusts, Schistocerca gregaria. Our results
      indicate that the youngest adults (2 weeks post-maturity) have a greater overall
      neurophysiological response to sound, especially for low frequencies (<10 kHz),
      as well as a shorter latency to this neural response. Interestingly, when
      measuring displacement of the tympanal membrane that the receptor neurons
      directly attach to, we found movement is not directly correlated with neural
      response. Therefore, we suggest the enhanced response in younger animals is due
      to the condition of their tissues (e.g. elasticity). Secondly, we found the sexes
      do not have the same responses, particularly at 4 weeks post-adult moult. We
      propose female reproductive condition reduces their ability to receive sounds.
      Overall our results indicate older animals, especially females, are less
      sensitive to sounds. 

PMID- 25944923
TI  - Consequences of calcium decline on the embryogenesis and life history of Daphnia
      magna.
AB  - Ambient calcium is declining in thousands of soft-water lake habitats in
      temperate regions as a consequence of unsustainable forestry practices, decreased
      atmospheric calcium deposition and acidic deposition. As their exoskeleton is
      heavily reinforced with calcium, freshwater crustaceans have a high specific
      calcium requirement relative to other aquatic organisms. Daphnia, in particular,
      is an ideal crustacean for investigating the consequences of calcium decline
      because it is an abundant and important member of freshwater zooplankton
      communities. Although it has been established that adult and juvenile Daphnia
      have different tolerances to low ambient calcium as a result of their different
      life stage-specific calcium requirements, the consequences of declining calcium
      on embryonic development have never been investigated. Here, we describe the
      distribution of calcium in embryonic stages of D. magna and introduce a novel and
      easy to use staging scheme. We tested whether calcium can be traced from mothers
      to their offspring. Finally, we assessed the fitness consequences of maternal
      provisioning in limiting calcium environments. We found that while embryos
      require calcium for their development and moulting, they do not equilibrate with
      environmental calcium levels. Instead, we were able to trace calcium from mothers
      to their offspring. Furthermore, our data strongly suggest that females are faced
      with an allocation trade-off between providing calcium to their offspring and
      using it for growth and moulting. Together, these data provide novel insights
      into the consequences of calcium decline for freshwater zooplankton. 

PMID- 25944924
TI  - No response to linear polarization cues in operant conditioning experiments with
      zebra finches.
AB  - Many animals can use the polarization of light in various behavioural contexts.
      Birds are well known to use information from the skylight polarization pattern
      for orientation and compass calibration. However, there are few controlled
      studies of polarization vision in birds, and the majority of them have not been
      successful in convincingly demonstrating polarization vision. We used a two
      alternative forced choice conditioning approach to assess linear polarization
      vision in male zebra finches in the 'visible' spectral range (wavelengths >400
      nm). The birds were trained to discriminate colour, brightness and polarization
      stimuli presented on either one of two LCD-screens. All birds were able to
      discriminate the colour and brightness stimuli, but they were unable to
      discriminate the polarization stimuli. Our results suggest that in the
      behavioural context studied here, zebra finches are not able to discriminate
      polarized light stimuli. 

PMID- 25944925
TI  - Differences between winter oilseed rape (Brassica napus L.) cultivars in nitrogen
      starvation-induced leaf senescence are governed by leaf-inherent rather than root
      derived signals.
AB  - Nitrogen (N) efficiency of winter oilseed rape (Brassica napus L.) line-cultivars
      (cvs.), defined as high grain yield under N limitation, has been primarily
      attributed to maintained N uptake during reproductive growth (N uptake
      efficiency) in combination with delayed senescence of the older leaves
      accompanied with maintained photosynthetic capacity (functional stay-green).
      However, it is not clear whether genotypic variation in N starvation-induced leaf
      senescence is due to leaf-inherent factors and/or governed by root-mediated
      signals. Therefore, the N-efficient and stay-green cvs. NPZ-1 and Apex were
      reciprocally grafted with the N-inefficient and early-senescing cvs. NPZ-2 and
      Capitol, respectively and grown in hydroponics. The senescence status of older
      leaves after 12 days of N starvation assessed by SPAD, photosynthesis and the
      expression of the senescence-specific cysteine protease gene SAG12-1 revealed
      that the stay-green phenotype of the cvs. NPZ-1 and Apex under N starvation was
      primarily under the control of leaf-inherent factors. The same four cultivars
      were submitted to N starvation for up to 12 days in a time-course experiment. The
      specific leaf contents of biologically active and inactive cytokinins (CKs) and
      the expression of genes involved in CK homeostasis revealed that under N
      starvation leaves of early-senescing cultivars were characterized by inactivation
      of biologically active CKs, whereas in stay-green cultivars synthesis,
      activation, binding of and response to biologically active CKs were favoured.
      These results suggest that the homeostasis of biologically active CKs was the
      predominant leaf-inherent factor for cultivar differences in N starvation-induced
      leaf senescence and thus N efficiency. 

PMID- 25944926
TI  - Replace, reuse, recycle: improving the sustainable use of phosphorus by plants.
AB  - The 'phosphorus problem' has recently received strong interest with two distinct
      strands of importance. The first is that too much phosphorus (P) is entering into
      waste water, creating a significant economic and ecological problem. Secondly,
      while agricultural demand for phosphate fertilizer is increasing to maintain crop
      yields, rock phosphate reserves are rapidly declining. Unravelling the mechanisms
      by which plants sense, respond to, and acquire phosphate can address both
      problems, allowing the development of crop plants that are more efficient at
      acquiring and using limited amounts of phosphate while at the same time improving
      the potential of plants and other photosynthetic organisms for nutrient recapture
      and recycling from waste water. In this review, we attempt to synthesize these
      important but often disparate parts of the debate in a holistic fashion, since
      solutions to such a complex problem require integrated and multidisciplinary
      approaches that address both P supply and demand. Rapid progress has been made
      recently in our understanding of local and systemic signalling mechanisms for
      phosphate, and of expression and regulation of membrane proteins that take
      phosphate up from the environment and transport it within the plant. We discuss
      the current state of understanding of such mechanisms involved in sensing and
      responding to phosphate stress. We also discuss approaches to improve the P-use
      efficiency of crop plants and future direction for sustainable use of P,
      including use of photosynthetic organisms for recapture of P from waste waters. 

PMID- 25944927
TI  - Local and distal effects of arbuscular mycorrhizal colonization on direct pathway
      Pi uptake and root growth in Medicago truncatula.
AB  - Two pathways exist for plant Pi uptake from soil: via root epidermal cells
      (direct pathway) or via associations with arbuscular mycorrhizal (AM) fungi, and
      the two pathways interact in a complex manner. This study investigated distal and
      local effects of AM colonization on direct root Pi uptake and root growth, at
      different soil P levels. Medicago truncatula was grown at three soil P levels in
      split-pots with or without AM fungal inoculation and where one root half grew
      into soil labelled with (33)P. Plant genotypes included the A17 wild type and the
      mtpt4 mutant. The mtpt4 mutant, colonized by AM fungi, but with no functional
      mycorrhizal pathway for Pi uptake, was included to better understand effects of
      AM colonization per se. Colonization by AM fungi decreased expression of direct
      Pi transporter genes locally, but not distally in the wild type. In mtpt4 mutant
      plants, direct Pi transporter genes and the Pi starvation-induced gene Mt4 were
      more highly expressed than in wild-type roots. In wild-type plants, less Pi was
      taken up via the direct pathway by non-colonized roots when the other root half
      was colonized by AM fungi, compared with non-mycorrhizal plants. Colonization by
      AM fungi strongly influenced root growth locally and distally, and direct root Pi
      uptake activity locally, but had only a weak influence on distal direct pathway
      activity. The responses to AM colonization in the mtpt4 mutant suggested that in
      the wild type, the increased P concentration of colonized roots was a major
      factor driving the effects of AM colonization on direct root Pi uptake. 

PMID- 25944929
TI  - Potential use of phytocystatins in crop improvement, with a particular focus on
      legumes.
AB  - Phytocystatins are a well-characterized class of naturally occurring protease
      inhibitors that function by preventing the catalysis of papain-like cysteine
      proteases. The action of cystatins in biotic stress resistance has been studied
      intensively, but relatively little is known about their functions in plant growth
      and defence responses to abiotic stresses, such as drought. Extreme weather
      events, such as drought and flooding, will have negative impacts on the yields of
      crop plants, particularly grain legumes. The concepts that changes in cellular
      protein content and composition are required for acclimation to different abiotic
      stresses, and that these adjustments are achieved through regulation of
      proteolysis, are widely accepted. However, the nature and regulation of the
      protein turnover machinery that underpins essential stress-induced cellular
      restructuring remain poorly characterized. Cysteine proteases are intrinsic to
      the genetic programmes that underpin plant development and senescence, but their
      functions in stress-induced senescence are not well defined. Transgenic plants
      including soybean that have been engineered to constitutively express
      phytocystatins show enhanced tolerance to a range of different abiotic stresses
      including drought, suggesting that manipulation of cysteine protease activities
      by altered phytocystatin expression in crop plants might be used to improve
      resilience and quality in the face of climate change. 

PMID- 25944928
TI  - Expression of potato RNA-binding proteins StUBA2a/b and StUBA2c induces
      hypersensitive-like cell death and early leaf senescence in Arabidopsis.
AB  - The Arabidopsis thaliana genome encodes three RNA-binding proteins (RBPs), UBP1
      associated protein 2a (UBA2a), UBA2b, and UBA2c, that contain two RNA-recognition
      motif (RRM) domains. They play important roles in wounding response and leaf
      senescence, and are homologs of Vicia faba abscisic-acid-activated protein kinase
      interacting protein 1 (VfAKIP1). The potato (Solanum tuberosum) genome encodes at
      least seven AKIP1-like RBPs. Here, two potato RBPs have been characterized,
      StUBA2a/b and StUBA2c, that are homologous to VfAKIP1 and Arabidopsis UBA2s.
      Transient expression of StUBA2s induced a hypersensitive-like cell death
      phenotype in tobacco leaves, and an RRM-domain deletion assay of StUBA2s revealed
      that the first RRM domain is crucial for the phenotype. Unlike overexpression of
      Arabidopsis UBA2s, constitutive expression of StUBA2a/b in Arabidopsis did not
      cause growth arrest and lethality at the young seedling stage, but induced early
      leaf senescence. This phenotype was associated with increased expression of
      defence- and senescence-associated genes, including pathogen-related genes (PR)
      and a senescence-associated gene (SAG13), and it was aggravated upon flowering
      and ultimately resulted in a shortened life cycle. Leaf senescence of StUBA2a/b
      Arabidopsis plants was enhanced under darkness and was accompanied by H2O2
      accumulation and altered expression of autophagy-associated genes, which likely
      cause cellular damage and are proximate causes of the early leaf senescence.
      Expression of salicylic acid signalling and biosynthetic genes was also
      upregulated in StUBA2a/b plants. Consistent with the localization of UBA2s-GFPs
      and VfAKIP1-GFP, soluble-modified GFP-StUBA2s localized in the nucleus within
      nuclear speckles. StUBA2s potentially can be considered for transgenic approaches
      to induce potato shoot senescence, which is desirable at harvest. 

PMID- 25944930
TI  - News feature: Microplastics present pollution puzzle.

PMID- 25944932
TI  - Correction for Liu et al., Solid-to-fluid-like DNA transition in viruses
      facilitates infection.

PMID- 25944933
TI  - Activity-dependent, homeostatic regulation of neurotransmitter release from
      auditory nerve fibers.
AB  - Information processing in the brain requires reliable synaptic transmission. High
      reliability at specialized auditory nerve synapses in the cochlear nucleus
      results from many release sites (N), high probability of neurotransmitter release
      (Pr), and large quantal size (Q). However, high Pr also causes auditory nerve
      synapses to depress strongly when activated at normal rates for a prolonged
      period, which reduces fidelity. We studied how synapses are influenced by
      prolonged activity by exposing mice to constant, nondamaging noise and found that
      auditory nerve synapses changed to facilitating, reflecting low Pr. For mice
      returned to quiet, synapses recovered to normal depression, suggesting that these
      changes are a homeostatic response to activity. Two additional properties, Q and
      average excitatory postsynaptic current (EPSC) amplitude, were unaffected by
      noise rearing, suggesting that the number of release sites (N) must increase to
      compensate for decreased Pr. These changes in N and Pr were confirmed
      physiologically using the integration method. Furthermore, consistent with
      increased N, endbulbs in noise-reared animals had larger VGlut1-positive puncta,
      larger profiles in electron micrographs, and more release sites per profile. In
      current-clamp recordings, noise-reared BCs had greater spike fidelity even during
      high rates of synaptic activity. Thus, auditory nerve synapses regulate
      excitability through an activity-dependent, homeostatic mechanism, which could
      have major effects on all downstream processing. Our results also suggest that
      noise-exposed bushy cells would remain hyperexcitable for a period after
      returning to normal quiet conditions, which could have perceptual consequences. 

PMID- 25944934
TI  - Destructin-1 is a collagen-degrading endopeptidase secreted by Pseudogymnoascus
      destructans, the causative agent of white-nose syndrome.
AB  - Pseudogymnoascus destructans is the causative agent of white-nose syndrome, a
      disease that has caused the deaths of millions of bats in North America. This
      psychrophilic fungus proliferates at low temperatures and targets hibernating
      bats, resulting in their premature arousal from stupor with catastrophic
      consequences. Despite the impact of white-nose syndrome, little is known about
      the fungus itself or how it infects its mammalian host. P. destructans is not
      amenable to genetic manipulation, and therefore understanding the proteins
      involved in infection requires alternative approaches. Here, we identify
      hydrolytic enzymes secreted by P. destructans, and use a novel and unbiased
      substrate profiling technique to define active peptidases. These experiments
      revealed that endopeptidases are the major proteolytic activities secreted by P.
      destructans, and that collagen, the major structural protein in mammals, is
      actively degraded by the secretome. A serine endopeptidase, hereby-named
      Destructin-1, was subsequently identified, and a recombinant form overexpressed
      and purified. Biochemical analysis of Destructin-1 showed that it mediated
      collagen degradation, and a potent inhibitor of peptidase activity was
      identified. Treatment of P. destructans-conditioned media with this antagonist
      blocked collagen degradation and facilitated the detection of additional secreted
      proteolytic activities, including aminopeptidases and carboxypeptidases. These
      results provide molecular insights into the secretome of P. destructans, and
      identify serine endopeptidases that have the clear potential to facilitate tissue
      invasion and pathogenesis in the mammalian host. 

PMID- 25944935
TI  - Platelet Gi protein Galphai2 is an essential mediator of thrombo-inflammatory
      organ damage in mice.
AB  - Platelets are crucial for hemostasis and thrombosis and exacerbate tissue injury
      following ischemia and reperfusion. Important regulators of platelet function are
      G proteins controlled by seven transmembrane receptors. The Gi protein Galpha(i2)
      mediates platelet activation in vitro, but its in vivo role in hemostasis,
      arterial thrombosis, and postischemic infarct progression remains to be
      determined. Here we show that mice lacking Galpha(i2) exhibit prolonged tail
      bleeding times and markedly impaired thrombus formation and stability in
      different models of arterial thrombosis. We thus generated mice selectively
      lacking Galpha(i2) in megakaryocytes and platelets (Gna(i2)(fl/fl)/PF4-Cre mice)
      and found bleeding defects comparable to those in global Galpha(i2)-deficient
      mice. To examine the impact of platelet Galpha(i2) in postischemic thrombo
      inflammatory infarct progression, Gna(i2)(fl/fl)/PF4-Cre mice were subjected to
      experimental models of cerebral and myocardial ischemia/reperfusion injury. In
      the model of transient middle cerebral artery occlusion stroke Gna(i2)(fl/fl)/PF4
      Cre mice developed significantly smaller brain infarcts and fewer neurological
      deficits than littermate controls. Following myocardial ischemia,
      Gna(i2)(fl/fl)/PF4-Cre mice showed dramatically reduced reperfusion injury which
      correlated with diminished formation of the ADP-dependent platelet neutrophil
      complex. In conclusion, our data provide definitive evidence that platelet
      Galpha(i2) not only controls hemostatic and thrombotic responses but also is
      critical for the development of ischemia/reperfusion injury in vivo.

PMID- 25944936
TI  - Regulation of oxygen delivery to the body via hypoxic vasodilation.

PMID- 25944937
TI  - The massive mitochondrial genome of the angiosperm Silene noctiflora is evolving
      by gain or loss of entire chromosomes.
AB  - Across eukaryotes, mitochondria exhibit staggering diversity in genomic
      architecture, including the repeated evolution of multichromosomal structures.
      Unlike in the nucleus, where mitosis and meiosis ensure faithful transmission of
      chromosomes, the mechanisms of inheritance in fragmented mitochondrial genomes
      remain mysterious. Multichromosomal mitochondrial genomes have recently been
      found in multiple species of flowering plants, including Silene noctiflora, which
      harbors an unusually large and complex mitochondrial genome with more than 50
      circular-mapping chromosomes totaling ~7 Mb in size. To determine the extent to
      which such genomes are stably maintained, we analyzed intraspecific variation in
      the mitochondrial genome of S. noctiflora. Complete genomes from two populations
      revealed a high degree of similarity in the sequence, structure, and relative
      abundance of mitochondrial chromosomes. For example, there are no inversions
      between the genomes, and there are only nine SNPs in 25 kb of protein-coding
      sequence. Remarkably, however, these genomes differ in the presence or absence of
      19 entire chromosomes, all of which lack any identifiable genes or contain only
      duplicate gene copies. Thus, these mitochondrial genomes retain a full gene
      complement but carry a highly variable set of chromosomes that are filled with
      presumably dispensable sequence. In S. noctiflora, conventional mechanisms of
      mitochondrial sequence divergence are being outstripped by an apparently
      nonadaptive process of whole-chromosome gain/loss, highlighting the inherent
      challenge in maintaining a fragmented genome. We discuss the implications of
      these findings in relation to the question of why mitochondria, more so than
      plastids and bacterial endosymbionts, are prone to the repeated evolution of
      multichromosomal genomes. 

PMID- 25944938
TI  - Capillary muscle.
AB  - The contraction of a muscle generates a force that decreases when increasing the
      contraction velocity. This "hyperbolic" force-velocity relationship has been
      known since the seminal work of A. V. Hill in 1938 [Hill AV (1938) Proc R Soc
      Lond B Biol Sci 126(843):136-195]. Hill's heuristic equation is still used, and
      the sliding-filament theory for the sarcomere [Huxley H, Hanson J (1954) Nature
      173(4412):973-976; Huxley AF, Niedergerke R (1954) Nature 173(4412):971-973]
      suggested how its different parameters can be related to the molecular origin of
      the force generator [Huxley AF (1957) Prog Biophys Biophys Chem 7:255-318;
      Deshcherevskii VI (1968) Biofizika 13(5):928-935]. Here, we develop a capillary
      analog of the sarcomere obeying Hill's equation and discuss its analogy with
      muscles. 

PMID- 25944939
TI  - Bench Comparative Assessment of Mechanically Assisted Cough Devices.
AB  - BACKGROUND: Mechanically assisted cough devices are used in patients with
      impaired cough to avoid secretion accumulation. We compared 5 mechanically
      assisted cough devices by bench testing using a breathing simulator and assessed
      their user-friendliness. METHODS: We measured inspiratory and expiratory airway
      pressures and peak expiratory flow, the strongest indicator of cough efficacy. We
      performed 2 bench tests: 1) to ascertain the differences between preset and
      actual settings in 3 different machines of each mechanically assisted cough
      device and 2) to assess the effects of varying respiratory impedance and air
      leaks on performance of the devices. We also evaluated the user-friendliness of
      the devices by measuring the time required and errors in accomplishing 4 tasks by
      10 physicians unfamiliar with mechanically assisted cough devices compared with
      product specialists from the distributing companies. Physicians also scored the
      ease of use. RESULTS: Four mechanically assisted cough devices during
      insufflation and all 5 during exsufflation showed differences between preset and
      actual airway pressures. All but one device showed uneven actual pressure values
      between models of the same type. Peak expiratory flow was significantly
      influenced by the mechanical properties in 2 devices and by air leaks in 4
      devices. The median time to accomplish all tasks by the product specialist (10
      [interquartile range of 2-29] s) was overall significantly shorter compared with
      all physicians (from 19 [14-65] to 36 [19-116] s). The number of procedural
      errors, but not the perceived ease of use, differed significantly between the
      devices. CONCLUSIONS: The performance of different mechanically assisted cough
      devices was erratic and included variance between models from the same
      manufacturer; it was affected by respiratory system impedance and air leaks. Time
      and rate of errors for performing procedures were elevated. These findings
      indicate that the devices are not interchangeable and that the settings should be
      targeted for each patient with the specific machine being used. Improvements in
      reliability, performance, and user-friendliness are advisable.

PMID- 25944941
TI  - Evaluation of Pressure Generated by Resistors From Different Positive Expiratory
      Pressure Devices.
AB  - BACKGROUND: Breathing exercises with positive expiratory pressure (PEP) are used
      to improve pulmonary function and airway clearance. Different PEP devices are
      available, but there have been no studies that describe the pressure generated by
      different resistors. The purpose of this study was to compare pressures generated
      from the proprietary resistor components of 4 commercial flow-dependent PEP
      valves with all other parameters kept constant. METHODS: Resistors from 4 flow
      regulated PEP devices (Pep/Rmt system, Wellspect HealthCare; Pipe P breathing
      exerciser, Koo Medical Equipment; Mini-PEP, Philips Respironics [including
      resistors by Rusch]; and 15-mm endo-adapter, VBM Medizintechnik) were tested
      randomly by a blinded tester at constant flows of 10 and 18 L/min from an
      external gas system. All resistors were tested 3 times. RESULTS: Resistors with a
      similar diameter produced statistically significant different pressures at the
      same flow. The differences were smaller when the flow was 10 L/min compared with
      18 L/min. The differences were also smaller when the diameter of the resistor was
      increased. The pressures produced by the 4 resistors of the same size were all
      significantly different when measuring 1.5- and 2.0-mm resistors at a flow of 10
      L/min and 2.0-mm resistors at a flow of 18 L/min (P < .001). There were no
      significant differences between any of the resistors when testing sizes of 4.5
      and 5.0 mm at either flow. The Mini-PEP and adapter resistors gave the highest
      pressures. CONCLUSIONS: Pressures generated by the different proprietary resistor
      components of 4 commercial PEP devices were not comparable, even though the
      diameter of the resistors is reported to be the same. The pressures generated
      were significantly different, particularly when using small-diameter resistors at
      a high flow. Therefore, the resistors may not be interchangeable. This is
      important information for clinicians, particularly when considering PEP for
      patients who do not tolerate higher pressures.

PMID- 25944940
TI  - Physiologic Effects of High-Flow Nasal Cannula Oxygen in Critical Care Subjects.
AB  - INTRODUCTION: High-flow nasal cannula (HFNC) can deliver heated and humidified
      gas (up to 100% oxygen) at a maximum flow of 60 L/min via nasal prongs or
      cannula. The aim of this study was to assess the short-term physiologic effects
      of HFNC. Inspiratory muscle effort, gas exchange, dyspnea score, and comfort were
      evaluated. METHODS: Twelve subjects admitted to the ICU for acute hypoxemic
      respiratory failure were prospectively included. Four study sessions were
      performed. The first session consisted of oxygen therapy given through a high
      FIO2, non-rebreathing face mask. Recordings were then obtained during periods of
      HFNC and CPAP at 5 cm H2O in random order, and final measurements were performed
      during oxygen therapy delivered via a face mask. Each of these 4 periods lasted
      ~20 min. RESULTS: Esophageal pressure signals, breathing pattern, gas exchange,
      comfort, and dyspnea were measured. Compared with the first session, HFNC reduced
      inspiratory effort (pressure-time product of 156.0 [119.2-194.4] cm H2O * s/min
      vs 204.2 [149.6-324.7] cm H2O * s/min, P < .01) and breathing frequency (P <
      .01). No significant differences were observed between HFNC and CPAP for
      inspiratory effort and breathing frequency. Compared with the first session,
      PaO2/FIO2 increased significantly with HFNC (167 [157-184] mm Hg vs 156 [110-171]
      mm Hg, P < .01). CPAP produced significantly greater PaO2/FIO2 improvement than
      did HFNC. Dyspnea improved with HFNC and CPAP, but this improvement was not
      significant. Subject comfort was not different across the 4 sessions.
      CONCLUSIONS: Compared with conventional oxygen therapy, HFNC improved inspiratory
      effort and oxygenation. In subjects with acute hypoxemic respiratory failure,
      HFNC is an alternative to conventional oxygen therapy. (ClinicalTrials.gov
      registration NCT01056952.).

PMID- 25944942
TI  - Decline in Lung Volume With Duchenne Muscular Dystrophy Is Associated With
      Ventilation Inhomogeneity.
AB  - BACKGROUND: Advanced stages of Duchenne muscular dystrophy (DMD) result in severe
      lung volume decline and are associated with high respiratory morbidity and
      mortality. The aim of this study was to investigate whether lung volume decline
      in subjects with DMD is associated with ventilation inhomogeneity measured with
      the multiple-breath washout technique. METHODS: This cross-sectional study of
      lung function included 45 subjects with DMD and 16 healthy controls using
      multiple-breath washout, spirometry, and cough peak flow. RESULTS: Subjects with
      DMD exhibited an elevated lung clearance index (> 7.0) defined as the cumulative
      exhaled volume divided by the functional residual capacity to lower the sulfur
      hexafluoride concentration below 2.5% compared with controls (8.16 +/- 2.55 vs
      6.23 +/- 0.46, P < .001). Lung clearance index elevation was negatively
      correlated with vital capacity (% predicted: r = -0.79, P < .001) and cough peak
      flow (L/min: r = -0.41, P = .005). Furthermore, dead-space ventilation (dead
      space-to-tidal-volume ratio) and functional residual capacity showed a positive
      correlation with lung clearance index elevation (r = 0.81 and 0.48, P < .001). An
      FVC of < 24% predicted lung clearance index elevation with a sensitivity of 96%
      and a specificity of 80%. CONCLUSIONS: Moderate-to-severe lung volume decline in
      subjects with DMD is associated with ventilation inhomogeneity. Lung clearance
      index elevation may be the result of altered ventilation geometry or retention of
      airway secretions in the infection-free DMD subject.

PMID- 25944943
TI  - Pharmacologic Agents That Promote Airway Clearance in Hospitalized Subjects: A
      Systematic Review.
AB  - Pharmacologic agents to promote mucus clearance may reduce the sequelae of
      obstructive secretions. We systematically reviewed comparative studies of
      pharmacologic agents for mucus clearance in hospitalized or postoperative
      subjects without cystic fibrosis and over 12 months of age. We searched MEDLINE
      and other databases from January 1970 to July 2014 to identify relevant
      literature. Two reviewers independently assessed each study against predetermined
      inclusion/exclusion criteria. Two reviewers also independently extracted data
      regarding subject and intervention characteristics and outcomes and assigned
      overall quality ratings. The 9 studies meeting review criteria included 5
      randomized controlled trials, 3 crossover randomized controlled trials, and one
      retrospective cohort study. Studies were small and together included a total of
      379 subjects (mean of 42 subjects per study). N-acetylcysteine, heparin plus N
      acetylcysteine, albuterol, ipratropium bromide, and saline were assessed. Studies
      reported no benefit of studied agents on expectoration, pulmonary function, and
      atelectasis and little effect on changes in sputum volume, weight, or viscosity.
      Adverse effects of agents were not consistently reported. Nausea was reported in
      2 studies of N-acetylcysteine (one paper reported 2 experiments and did not
      clearly identify in which experiment adverse effects occurred), 3 studies
      reported that there were no adverse events, and 3 studies did not address adverse
      effects at all. Further research with clearly characterized populations and
      interventions is needed to understand the potential benefits and adverse effects
      of mucoactive agents. 

PMID- 25944944
TI  - Computerized Dead-Space Volume Measurement of Face Masks Applied to Simulated
      Faces.
AB  - BACKGROUND: The dead-space volume (VD) of face masks for metered-dose inhaler
      treatments is particularly important in infants and young children with asthma,
      who have relatively low tidal volumes. Data about VD have been traditionally
      obtained from water displacement measurements, in which masks are held against a
      flat surface. Because, in real life, masks are placed against the face, VD is
      likely to differ considerably between masks depending upon their contour and fit.
      The aim of this study was to develop an accurate and reliable way to measure VD
      electronically and to apply this technique by comparing the electronic VD of
      commonly available face masks. METHODS: Average digital faces were obtained from
      3-dimensional images of 270 infants and children. Commonly used face masks (small
      and medium) from various manufacturers (Monaghan Medical, Pari Respiratory
      Equipment, Philips Respironics, and InspiRx) were scanned and digitized by means
      of computed tomography. Each mask was electronically applied to its respective
      digital face, and the VD enclosed (mL) was computerized and precisely measured.
      RESULTS: VD varied between 22.6 mL (SootherMask, InspiRx) and 43.1 mL (Vortex,
      Pari) for small masks and between 41.7 mL (SootherMask) and 71.5 mL (AeroChamber,
      Monaghan Medical) for medium masks. These values were significantly lower and
      less variable than measurements obtained by water displacement. CONCLUSIONS:
      Computerized techniques provide an innovative and relatively simple way of
      accurately measuring the VD of face masks applied to digital faces. As determined
      by computerized measurement using average-size virtual faces, the InspiRx masks
      had a significantly smaller VD for both small and medium masks compared with the
      other masks. This is of considerable importance with respect to aerosol dose and
      delivery time, particularly in young children. (ClinicalTrials.gov registration
      NCT01274299.).

PMID- 25944945
TI  - Endotracheal Tube Seal and Suction Performance in a Novel Biorealistic Tracheal
      Model.
AB  - BACKGROUND: Endotracheal tube (ETT) cuffs create a seal to protect against
      secretion entry to the lungs. Cuff inflation currently is recommended at 20-30 cm
      H2O pressure. ETT designs have variable seal performance in bench studies using
      rigid tracheal models lacking the dynamic characteristics of the human trachea.
      We compared ETT designs within a new, biorealistic tracheal model to assess cuff
      and suction performance in the setting of a compliant trachea. METHODS: Three ETT
      designs (Mallinckrodt Hi-Lo, KimVent Microcuff, and Sheridan/HVT) were tested for
      performance by simulant leakage below the cuff and air leakage (measured as
      return tidal volume >= 80% delivered) over a range of cuff (5-25 cm H2O) and end
      expiratory pressure (PEEP 0-15 cm H2O). Subglottic suction channel performance
      was tested in 2 ETTs (TaperGuard Evac [Covidien] and ISIS HVT [Teleflex]) as time
      to evacuate the simulant. RESULTS: All ETT cuffs provided effective seals at an
      inflation pressure of 12 cm H2O when PEEP was <= 5 cm H2O. The Microcuff ETT
      sealed at the lowest pressure of 6 cm H2O, whereas the Sheridan/HVT cuff sealed
      at 12 cm H2O (P = .01). With a PEEP of 15 cm H2O, a reciprocal increase in air
      leak occurred, requiring a cuff inflation up to 22 cm H2O to maintain a return
      tidal volume at >= 80% delivered. Suction channel performance improved in the
      lateral position compared with supine for both ETT designs during continuous 15
      mm Hg suction pressure (P = .001). CONCLUSIONS: Within a novel model with normal
      trachea compliance, we found all ETT designs tested to seal at lower than current
      recommended cuff pressures.

PMID- 25944946
TI  - Intratracheal albuterol: a potential intervention for the asthma toolbox.

PMID- 25944947
TI  - Therapist-driven protocols: new incentives for change.

PMID- 25944948
TI  - Implementation of an inhaled nitric oxide protocol: a paradox or the perfect
      pair?

PMID- 25944949
TI  - The American Thoracic Society/European Respiratory Society acceptability criteria
      for spirometry: asking too much or not enough?

PMID- 25944950
TI  - The American Thoracic Society/European Respiratory Society acceptability criteria
      for spirometry: asking too much or not enough?--Reply.

PMID- 25944952
TI  - Biomarkers in assessing disease activity in patients with eosinophilic
      granulomatosis with polyangiitis.

PMID- 25944954
TI  - Radionuclide content of NORM by-products originating from the coal-fired power
      plant in Oroszlany (Hungary).
AB  - At the Thermal Power Plant in Oroszlany (Hungary), a huge amount of by-products
      have been produced since 1961. In this survey, coal and other by-products were
      examined (fly ash, bottom ash, fluidised bed bottom ash, gypsum and slurry-type
      ash). The natural isotopes were determined using an HPGe detector. It was found
      that the radionuclide content of coal was significantly lower ((226)Ra = 45.3+/
      6.3, (232)Th = 26.3+/-5.7 and (40)K = 210+/-21 Bq kg(-1)) than that in the case
      of ashes other than the fluidised type. The average values of the bottom ash
      deposited in the largest quantities-were three times higher than those for coal
      ((226)Ra = 144+/-18, (232)Th = 84.3+/-14 and (40)K = 260+/-25 Bq kg(-1)). In the
      case of fractionised bottom ash, the radionuclide content of <0.1 mm was 45 %
      higher than that of >1.6 mm and the massic radon exhalation of <0.1 mm was
      approximately four times higher than that above this range. 

PMID- 25944953
TI  - Analyses of local dose distributions in the lungs for the determination of risk
      apportionment factors.
AB  - For radiation protection purposes, the relative contributions of bronchial (BB),
      bronchiolar (bb) and alveolar-interstitial (AI) doses to lung cancer risk are
      represented by their corresponding apportionment factors. The current assumption
      of equal apportionment factors can be tested by comparing different radon and
      thoron progeny exposures, which produce different regional dose distributions,
      with the pathologically observed regional cancer distributions: (1) radon progeny
      inhalation, (2) thoron progeny inhalation, (3) thoron and thoron progeny
      exhalation (Thorotrast patients) and (4) RP inhalation in rats, and cigarette
      smoke inhalation as smoking is the dominant cause of lung cancer. Comparison with
      the pathologically observed regional cancer distributions suggests (1) a smaller
      apportionment factor for the AI region as compared with BB and bb regions and (2)
      a higher value for the BB region relative to that for the bb region. 

PMID- 25944955
TI  - Non-destructive determination of uranium, thorium and 40K in tobacco and their
      implication on radiation dose levels to the human body.
AB  - The naturally occurring radionuclides of (235)U, (238)U and (232)Th and their
      daughter products are a potential major source of anthropogenic radiation to
      tobacco smokers. Often overlooked is the presence of (40)K in tobacco and its
      implication to radiation dose accumulation in the human body. In this study,
      these three radiation sources have been determined in four typical US cigarettes
      using neutron activation analysis (NAA). The NAA reactions of
      (238)U(n,gamma)(239)U, (232)Th(n,gamma)(233)Th and (41)K(n,gamma)(42)K were used
      to determine (235)U, (238)U and (232)Th and (40)K, respectively. The activity of
      (238)U can easily be determined by epithermal NAA of the (238)U(n,gamma)(239)U
      reaction, and the activity of (235, 234)U can easily be deduced. Using isotopic
      ratios, the activity due to (40)K was found by the determined concentrations of
      (41)K (also by epithermal neutrons) in the bulk material. Each gram of total
      potassium yields 30 Bq of (40)K. The annual effective dose for smokers using 20
      cigarettes per day was calculate to be 14.6, 137 and 9 MUSv y(-1) for (238,235,)
      (234)U, (232)Th and (40)K, respectively. These values are significantly lower
      that the dose received from (210)Po except for (232)Th. 

PMID- 25944956
TI  - Equivalence of pure propane and propane TE gases for microdosimetric
      measurements.
AB  - A tissue-equivalent proportional counter (TEPC) simulates micrometric volumes of
      tissue if the energy deposited in the counter cavity is the same as that in the
      tissue volume. Nevertheless, a TEPC measures only the ionisations created in the
      gas, which are later converted into imparted energy. Therefore, the equivalence
      of the simulated diameter (Drho) in two gases should be based on the equality of
      the mean number of ions pairs in the gas rather than on the imparted energy.
      Propane-based tissue-equivalent gas is the most commonly used gas mixture at
      present, but it has the drawback that its composition may change with time. From
      this point of view, the use of pure propane offers practical advantages: higher
      gas gain and longer stability. In this work, microdosimetric measurements
      performed with pure propane, at site sizes 0.05 mg cm(-2) <= Drho <= 0.3 mg cm(
      2), demonstrate that the response of a propane-filled detector in gamma and in
      neutron fields is almost the same if an appropriate gas density is used. 

PMID- 25944957
TI  - Evaluation of dose conversion coefficients for external exposure using Taiwanese
      reference man and woman.
AB  - Reference man has been widely used for external and internal dose evaluation of
      radiation protection. The parameters of the mathematical model of organs
      suggested by the International Commission of Radiological Protection (ICRP) are
      adopted from the average data of Caucasians. However, the organ masses of Asians
      are significantly different from the data of Caucasians, leading to potentially
      dosimetric errors. In this study, a total of 40 volunteers whose heights and
      weights corresponded to the statistical average of Taiwanese adults were
      recruited. Magnetic resonance imaging was performed, and T2-weighted images were
      acquired. The Taiwanese reference man and woman were constructed according to the
      measured organ masses. The dose conversion coefficients (DCFs) for anterior
      posterior (AP), posterior-anterior (PA), right lateral (RLAT) and left lateral
      (LLAT) irradiation geometries were simulated. For the Taiwanese reference man,
      the average differences of the DCFs compared with the results of ICRP-74 were
      7.6, 5.1 and 11.1 % for 0.1, 1 and 10 MeV photons irradiated in the AP direction.
      The maximum difference reached 51.7 % for the testes irradiated by 10 MeV
      photons. The size of the trunk, the volume and the geometric position of organs
      can cause a significant impact on the DCFs for external exposure of radiation.
      The constructed Taiwanese reference man and woman can be used in radiation
      protection to increase the accuracy of dose evaluation for the Taiwanese
      population. 

PMID- 25944958
TI  - Vertical distribution of radiation dose rates in the water of a brackish lake in
      Aomori Prefecture, Japan.
AB  - Seasonal radiation dose rates were measured with glass dosemeters housed in
      watertight cases at various depths in the water of Lake Obuchi, a brackish lake
      in Aomori Prefecture, Japan, during fiscal years 2011-2013 to assess the
      background external radiation dose to aquatic biota in the lake. The mean
      radiation dose in the surface water of the lake was found to be 27 nGy h(-1),
      which is almost the same as the absorption dose rate due to cosmic ray reported
      in the literature. Radiation dose rates decreased exponentially with water depth
      down to a depth of 1 m above the bottom sediment. In the water near the sediment,
      the dose rate increased with depth owing to the emission of gamma-rays from
      natural radionuclides in the sediment. 

PMID- 25944959
TI  - Tritium activity concentrations and residence times of groundwater collected in
      Rokkasho, Japan.
AB  - Tritium ((3)H) concentrations were measured in groundwater samples from four
      surface wells (4-10 m deep), four shallow wells (24-26.5 m deep) and a 150-m-deep
      well in the Futamata River catchment area, which is adjacent to the large-scale
      commercial spent nuclear fuel reprocessing plant in Rokkasho, Japan. The (3)H
      concentrations in most of the surface- and shallow-well samples (<0.03-0.57 Bq l(
      1)) were similar to those in precipitation (annual mean: 0.31-0.79 Bq l(-1)),
      suggesting that the residence time of the water in those wells was 0-15 y. The
      (3)H concentrations in the samples from a 26-m-deep well and the 150-m-deep well
      were lower than those in the other wells, indicating that groundwater with a long
      residence time exists in deep aquifers and the estuary area of the catchment. It
      is not clear whether (3)H released during test operation of the plant with actual
      spent nuclear fuel affected the (3)H concentrations observed in this study. 

PMID- 25944960
TI  - Determination of 137Cs and 60Co pollution in the area of the Laguna Verde Nuclear
      Power Plant, Mexico.
AB  - The project 'Radiological Analysis of Environmental Samples in the Gulf of Mexico
      and the coast of Quintana Roo', had the aim of identifying and quantifying
      anthropogenic radionuclides in environmental samples consisting of silt, sand and
      sea water. This paper presents the results of the radiological analysis of these
      samples, which was made in the multichannel system for gamma spectrometry with
      hyperpure germanium detector in the Laboratory of Radiological Analysis of
      Environmental Samples, located at the Physics Department, Faculty of Sciences, of
      the Autonomous National University of Mexico (UNAM). The sampled points are along
      the coast of the contiguous states of Tamaulipas, Veracruz, Tabasco, Campeche,
      Yucatan and Quintana Roo. This paper presents the qualitative and quantitative
      concentrations of the main identified anthropogenic radionuclides (60)Co and
      (137)Cs. 

PMID- 25944961
TI  - Radiation exposure to the eye lens of orthopaedic surgeons during various
      orthopaedic procedures.
AB  - The aim of the present study was to assess the radiation dose to the eye lens of
      orthopaedic surgeons during various orthopaedic procedures and to make efforts to
      ensure that radiation protection is optimised. The study was performed for
      Fractura femoris and Fractura cruris procedures performed in orthopaedic
      operating theatres, as well as for fractures of wrist, ankle and hand/shoulder
      performed in the emergency trauma room. The highest mean value of the eye lens
      dose of 47.2 MUSv and higher mean fluoroscopy time of 3 min, as well as the
      corresponding highest maximum values of 77.1 MUSv and 5.0 min were observed for
      the Fractura femoris procedure performed with the Biplanar 500e fluoroscopy
      systems. At a normal workload, the estimated mean annual dose values do not
      exceed the annual occupational dose limit for the lens of eye, but at a heavy
      workload in the department, this dose limit could be achieved or exceeded. The
      use of protective lead glasses is recommended as they could reduce the radiation
      exposure of the lens of the eye. The phantom measurements demonstrated that the
      use of half-dose mode could additionally reduce dose to the operator's eye lens.

PMID- 25944962
TI  - Absorbed dose rate in air in metropolitan Tokyo before the Fukushima Daiichi
      Nuclear Power Plant accident.
AB  - The monitoring of absorbed dose rate in air has been carried out continually at
      various locations in metropolitan Tokyo after the accident of the Fukushima
      Daiichi Nuclear Power Plant. While the data obtained before the accident are
      needed to more accurately assess the effects of radionuclide contamination from
      the accident, detailed data for metropolitan Tokyo obtained before the accident
      have not been reported. A car-borne survey of the absorbed dose rate in air in
      metropolitan Tokyo was carried out during August to September 2003. The average
      absorbed dose rate in air in metropolitan Tokyo was 49+/-6 nGy h(-1). The
      absorbed dose rate in air in western Tokyo was higher compared with that in
      central Tokyo. Here, if the absorbed dose rate indoors in Tokyo is equivalent to
      that outdoors, the annual effective dose would be calculated as 0.32 mSv y(-1). 

PMID- 25944963
TI  - Assessment of gamma dose rate in dwellings due to decorative stones.
AB  - For more accurate assessment of the enhanced external exposure to dwellers caused
      by decorative stones, based on a model room and different decorative conditions,
      the 3-D distributions of indoor gamma dose rates were computed by the Monte Carlo
      simulations, and a new model was established to estimate the extra gamma dose
      rate at the centre of the room in this study. For verification of the simulation
      results, the gamma radiation was both instantaneously and cumulatively measured
      in a test room. The results showed that both the gamma dose rate at the centre of
      the room and the distribution of indoor gamma radiation were in general agreement
      with the simulated ones. 

PMID- 25944964
TI  - Baseline data of naturally occurring radionuclides in some native vegetables and
      fruits in Southern Thailand.
AB  - The aim of this study was to provide the baseline data information on natural
      radioactivities in vegetables and fruits produced and consumed locally in the
      areas of potential nuclear power plant sites in Thailand. Four provinces (Prajuab
      Kirikhan, Chumphon, Surat-Thani and Nakhon-Si-thammarat) were selected for
      collection of native vegetables and fruits samples, together with their
      corresponding soils. The activities of (226)Ra, (228)Ra, (40)K and (210)Po were
      determined in all these samples. The obtained results for (226)Ra, (228)Ra, (40)K
      and (210)Po for all vegetable and fruit samples were in the range of 1-34, 1-108,
      32-4392 and 0.2-47 Bq kg(-1), respectively, which were much lower than those
      obtained for their corresponding soils. 

PMID- 25944966
TI  - Bacteria repelling on highly-ordered alumina-nanopore structures.
AB  - Bacteria introduce diseases and infections to humans by their adherence to
      biomaterials, such as implants and surgical tools. Cell desorption is an
      effective step to reduce such damage. Here, we report mechanisms of bacteria
      desorption. An alumina nanopore structure (ANS) with pore size of 35 nm, 55 nm,
      70 nm, and 80 nm was used as substrate to grow Escherichia coli (E. coli) cells.
      A bacteria repelling experimental method was developed to quantitatively evaluate
      the area percentage of adherent bacterial cells that represent the nature of cell
      adhesion as well as desorption. Results showed that there were two crucial
      parameters: contact angle and contact area that affect the adhesion/desorption.
      The cells were found to be more easily repelled when the contact angle increased.
      The area percentage of adherent bacterial cells decreased with the decrease in
      the contact area of a cell on ANS. This means that cell accessibility on ANS
      depends on the contact area. This research reveals the effectiveness of the
      nanopored structures in repelling cells.

PMID- 25944967
TI  - Point-of-care testing: High time for a dedicated National Adverse Event
      Monitoring System.

PMID- 25944965
TI  - Gender-specific modulation of neural mechanisms underlying social reward
      processing by Autism Quotient.
AB  - Autism spectrum disorder refers to a neurodevelopmental condition primarily
      characterized by deficits in social cognition and behavior. Subclinically,
      autistic features are supposed to be present in healthy humans and can be
      quantified using the Autism Quotient (AQ). Here, we investigated a potential
      relationship between AQ and neural correlates of social and monetary reward
      processing, using functional magnetic resonance imaging in young, healthy
      participants. In an incentive delay task with either monetary or social reward,
      reward anticipation elicited increased ventral striatal activation, which was
      more pronounced during monetary reward anticipation. Anticipation of social
      reward elicited activation in the default mode network (DMN), a network
      previously implicated in social processing. Social reward feedback was associated
      with bilateral amygdala and fusiform face area activation. The relationship
      between AQ and neural correlates of social reward processing varied in a gender
      dependent manner. In women and, to a lesser extent in men, higher AQ was
      associated with increased posterior DMN activation during social reward
      anticipation. During feedback, we observed a negative correlation of AQ and right
      amygdala activation in men only. Our results suggest that social reward
      processing might constitute an endophenotype for autism-related traits in healthy
      humans that manifests in a gender-specific way. 

PMID- 25944968
TI  - Reducing post analytical error: perspectives on new formats for the blood
      sciences pathology report.
AB  - Little has changed in the way we report pathology results from blood sciences
      over the last 50 years other than moving to electronic display from paper. In
      part, this is aspiration to preserve the format of a paper report in electronic
      format. It is also due to the limitations of electronic media to display the
      data. The advancement of web-based technologies and functionality of hand-held
      devices together with wireless and other technologies afford the opportunity to
      rethink data presentation with the aim of emphasising the message in the data,
      thereby modifying clinical behaviours and potentially reducing post-analytical
      error. This article takes the form of a commentary which explores new
      developments in the field of infographics and, together with examples, suggests
      some new approaches to communicating what is currently just data into
      information. The combination of graphics and a new approach to provocative
      interpretative commenting offers a powerful tool in improving pathology
      utilisation. An additional challenge is the requirement to consider how pathology
      reports may be issued directly to patients. 

PMID- 25944969
TI  - Managing the Ethical Issues of Genomic Research using Pathology Specimens.
AB  - Biobanks of human biospecimens involving tissue taken from surgery require close
      relationships with diagnostic pathology practices. As most of the tissue will be
      analysed using genetic or genomic technologies there is the possibility that new
      information is created that could be of relevance to the donors. Although
      attention has been recently focused on the responsibilities that may arise from
      researchers and biobanks in terms of giving back individual genetic research
      results (IGRRs) to research participants, little has been said in relation to the
      role of pathology services. In this Commentary, we summarise the issues with
      respect to pathology services and what guidelines and professional practice
      documents say about their responsibilities. We also provide points to consider in
      the development of an ethically defensible plan for giving back individual
      research results. 

PMID- 25944970
TI  - Association of high expression of Grobeta with clinical and pathological
      characteristics of unfavorable prognosis in gastrointestinal stromal tumors.
AB  - GRObeta (CXCL2) is a chemokine produced by endotoxin-treated macrophages that
      mediates inflammation and tumor development. However, little is known about
      GRObeta expression in gastrointestinal stromal tumors (GIST) or the relationship
      between GRObeta expression and clinical attributes of GIST. GRObeta expression
      was examined via immunohistochemical staining of 173 GIST samples using tissue
      microarray. The relationship between GRObeta expression and relevant patient and
      tumor characteristics was assessed, using chi-square tests. Univariate and
      multivariate analysis was carried out using the Cox regression method. High
      GRObeta cytoplasm staining was detected in 56 (32.4%) specimens; high GRObeta
      nuclear staining was detected in 64 (37.0%) specimens. High GRObeta cytoplasm
      staining was significantly associated with patients' age (P = 0.043) and tumor
      location (P = 0.014), while high GRObeta nucleus staining was significantly
      associated with mitotic index (P = 0.034), tumor location (P = 0.049), and AFIP
      Miettinen risk classification (P = 0.048). Kaplan-Meier survival curves showed
      GIST patients with low GRObeta cytoplasm expression (P = 0.023) and mitotic index
      < 6 per 50 HPFs (P = 0.026) to have a more favorable prognosis. These findings
      indicate that GRObeta expression correlates with malignant GIST phenotypes and
      could be an unfavorable prognostic marker in patients with GIST. 

PMID- 25944971
TI  - Characterization of clinical and genetic risk factors associated with
      dyslipidemia after kidney transplantation.
AB  - We determined the prevalence of dyslipidemia in a Japanese cohort of renal
      allograft recipients and investigated clinical and genetic characteristics
      associated with having the disease. In total, 126 patients that received renal
      allograft transplants between February 2002 and August 2011 were studied, of
      which 44 recipients (34.9%) were diagnosed with dyslipidemia at 1 year after
      transplantation. Three clinical factors were associated with a risk of having
      dyslipidemia: a higher prevalence of disease observed among female than male
      patients (P = 0.021) and treatment with high mycophenolate mofetil (P = 0.012)
      and prednisolone (P = 0.023) doses per body weight at 28 days after
      transplantation. The genetic association between dyslipidemia and 60 previously
      described genetic polymorphisms in 38 putative disease-associated genes was
      analyzed. The frequency of dyslipidemia was significantly higher in patients with
      the glucocorticoid receptor (NR3C1) Bcl1 G allele than in those with the CC
      genotype (P = 0.001). A multivariate analysis revealed that the NR3C1 Bcl1 G
      allele was a significant risk factor for the prevalence of dyslipidemia (odds
      ratio = 4.6; 95% confidence interval = 1.8-12.2). These findings may aid in
      predicting a patient's risk of developing dyslipidemia. 

PMID- 25944972
TI  - CYP7A1 gene polymorphism located in the 5' upstream region modifies the risk of
      coronary artery disease.
AB  - BACKGROUND: 7-Alpha cholesterol hydroxylase (CYP7A1), the first enzyme of classic
      conversion pathway leading from cholesterol to bile acids synthesis, is encoded
      by CYP7A1 gene. Its single nucleotide polymorphisms (SNPs) influence serum lipid
      levels and may be related to impaired lipid profile leading to coronary artery
      disease (CAD). The aim of the present study was to analyze the possible
      association between the rs7833904 CYP7A1 polymorphism and premature CAD. MATERIAL
      AND METHODS: Serum lipid levels and rs7833904 SNP were determined in 419
      subjects: 200 patients with premature CAD and 219 age and sex matched controls.
      RESULTS: The A allele carrier state was associated with CAD (OR = 1.76, 95% CI;
      1.14-2.71, P = 0.014). The effect was even stronger in the male subgroups (OR =
      2.16, 95% CI; 1.28-3.65, P = 0.003). There was no effect in the females. Risk
      factors of CAD and clinical phenotype of atherosclerosis were not associated with
      genotype variants of the rs7833904 SNP. Lipid profiles also did not differ
      significantly between individual genotypes. CONCLUSION: The CYP7A1 rs7833904
      polymorphism may modify the risk of CAD. This effect is especially strong in male
      subjects. The studied polymorphism does not significantly influence serum lipid
      levels, in the present study.

PMID- 25944973
TI  - Vimentin 3, the new hope, differentiating RCC versus oncocytoma.
AB  - Vimentin is currently used to differentiate between malignant renal carcinomas
      and benign oncocytomas. Recent reports showing Vimentin positive oncocytomas
      seriously question the validity of this present diagnostic approach. Vimentin 3
      is a spliced variant and ends with a unique C-terminal ending after exon 7 which
      differentiates it from the full length version that has 9 exons. Therefore, the
      protein size is different; the full length Vimentin version has a protein size of
      ~57 kDa and the truncated version of ~47 kDa. We designed an antibody, called
      Vim3, against the unique C-terminal ending of the Vimentin 3 variant. Using
      immune histology, immune fluorescence, Western blot, and qRT-PCR analysis, a Vim3
      overexpression was detectable exclusively in oncocytoma, making the detection of
      Vim3 a potential specific marker for benign kidney tumors. This antibody is the
      first to clearly differentiate benign oncocytoma and the mimicking eosinophilic
      variants of the RCCs. This differentiation between malignant and benign RCCs is
      essential for operative planning, follow-up therapy, and patients' survival. In
      the future the usage of Vimentin antibodies in routine pathology has to be
      applied with care. Consideration must be given to Vimentin specific binding
      epitopes otherwise a misdiagnosis of the patients' tumor samples may result. 

PMID- 25944974
TI  - The relationship between clinical feature, complex immunophenotype, chromosome
      karyotype, and outcome of patients with acute myeloid leukemia in China.
AB  - Mixed phenotype acute leukemia (MPAL) is a complex entity expressing both
      lymphoid and myeloid immunophenotyping. In the present study, 47 MPAL, 60
      lymphoid antigen-positive acute myeloid leukemia (Ly(+)AML), and 90 acute myeloid
      leukemia with common myeloid immunophenotype (Ly(-)AML) patients were
      investigated. We found that, in MPAL patients, there were high proportions of
      blast cells in bone marrow and incidence of hepatosplenomegaly, lymphadenopathy,
      and Philadelphia chromosome. The overall survival (OS) and relapse-free survival
      (RFS) in MPAL patients were significantly shorter than those in Ly(+)AML and Ly(
      )AML. With regard to the patients with normal karyotype only, the OS and RFS of
      MPAL were significantly lower than those of the Ly(+)AML and Ly(-)AML; but there
      were no significant differences in OS and RFS among the patients with complex
      karyotype. The OS rates of 3 groups with complex karyotype were lower than those
      of patients with normal karyotype. In Cox multivariate analysis, complex
      karyotype was an independent pejorative factor for both OS and RFS. Therefore,
      MPAL is confirmed to be a poor-risk disease while Ly(+)AML does not impact
      prognosis. Complex karyotype is an unfavorable prognosis factor in AML patients
      with different immunophenotype. Mixed immunophenotype and complex karyotype
      increase the adverse risk when they coexist. 

PMID- 25944975
TI  - Chaperonin-containing t-complex protein-1 subunit beta as a possible biomarker
      for the phase of glomerular hyperfiltration of diabetic nephropathy.
AB  - In cell model, we discovered the association between chaperonin-containing t
      complex polypeptide 1 subunit beta (TCP-1beta) and early diabetic nephropathy
      (DN). In this study, we further explored the relationships between TCP-1beta and
      type 2 diabetic mellitus (DM). To mimic the clinical hyperfiltration state, a
      type 2 DM mice model was established by feeding a high-fat diet in combination
      with treatment of streptozotocin and nicotinamide. Blood and urine were collected
      to determine creatinine clearance (C cr), and kidney tissues were harvested for
      evaluation of TCP-1beta expression by immunohistochemistry and Western blot.
      Meanwhile, clinical subjects of healthy controls and type 2 DM were recruited to
      strengthen the evidence with urine TCP-1beta. Results showed that C cr and the
      expression of TCP-1beta in kidney were significantly higher one week after
      hyperglycemia development, suggesting that the hyperfiltration state was
      successfully established in the mice model. TCP-1beta was expressed predominantly
      on renal tubules. By using the estimated glomerular filtration rate to index
      progression in clinical investigation, urine TCP-1beta level was associated with
      the hyperfiltration phase in type 2 DM patients. Conclusively, we confirmed that
      TCP-1beta is a possible biomarker for early nephropathy of type 2 DM, but further
      mechanistic study to elucidate its cause and pathway is needed. 

PMID- 25944977
TI  - Do Biotech Patent Lawsuits Really "Overwhelmingly Lose?": A Response to Our
      Divided Patent System.

PMID- 25944978
TI  - Assessment of early cognitive impairment in patients with clinically isolated
      syndromes and multiple sclerosis.
AB  - Objective. The aim of our study was to investigate the frequency and pattern of
      cognitive impairment in patients with clinically isolated syndromes and definite
      diagnosis of multiple sclerosis within the last 2 years. Methods. We assessed the
      cognitive status of 46 patients aged 18-49 years with clinically isolated
      syndromes or definite diagnosis of multiple sclerosis who have onset of their
      symptoms within the last 2 years. Patients were matched with 40 healthy
      participants for age, sex, and educational level. Neuropsychological assessment
      was performed by stroop test, paced auditory serial addition test (PASAT),
      controlled oral word association test (COWAT), clock drawing test, trail making
      test (TMT), faces symbol test (FST). Hamilton Depression Scale and Modified
      Fatigue Impact Scale were used to quantify the severity of any depression and
      fatigue the subjects might suffer. Results. 19.6% of early MS/CIS group failed at
      4 and more tests and had significant cognitive impairment focused on attention,
      executive functions, memory, and learning. No significant relationship was found
      between cognitive impairment and disability and fatigue scores. Discussion.
      Cognitive impairment can be present from the earliest stage of multiple
      sclerosis. It should be considered among the main manifestations of MS even in
      the earliest stages of the disease. 

PMID- 25944976
TI  - Cardiovascular biomarkers in chronic kidney disease: state of current research
      and clinical applicability.
AB  - The high incidence of cardiovascular events in chronic kidney disease (CKD)
      warrants an accurate evaluation of risk aimed at reducing the burden of disease
      and its consequences. The use of biomarkers to identify patients at high risk has
      been in use in the general population for several decades and has received mixed
      reactions in the medical community. Some practitioners have become staunch
      supporters and users while others doubt the utility of biomarkers and rarely
      measure them. In CKD patients numerous markers similar to those used in the
      general population and others more specific to the uremic population have
      emerged; however their utility for routine clinical application remains to be
      fully elucidated. The reproducibility and standardization of the serum assays are
      serious limitations to the broad implementation of these tests. The lack of
      focused research and validation in randomized trials rather than ad hoc
      measurement of multiple serum markers in observational studies is also cause for
      concern related to the clinical applicability of these markers. We review the
      current literature on biomarkers that may have a relevant role in field of
      nephrology. 

PMID- 25944979
TI  - Mast cell and autoimmune diseases.
AB  - Mast cells are important in innate immune system. They have been appreciated as
      potent contributors to allergic reaction. However, increasing evidence implicates
      the important role of mast cells in autoimmune disease like rheumatoid arthritis
      and multiple sclerosis. Here we review the current stage of knowledge about mast
      cells in autoimmune diseases. 

PMID- 25944980
TI  - Gut inflammation and immunity: what is the role of the human gut virome?
AB  - The human virome comprises viruses that infect host cells, virus-derived elements
      in our chromosomes, and viruses that infect other organisms, including
      bacteriophages and plant viruses. The development of high-throughput sequencing
      techniques has shown that the human gut microbiome is a complex community in
      which the virome plays a crucial role into regulation of intestinal immunity and
      homeostasis. Nevertheless, the size of the human virome is still poorly
      understood. Indeed the enteric virome is in a continuous and dynamic equilibrium
      with other components of the gut microbiome and the gut immune system, an
      interaction that may influence the health and disease of the host. We review
      recent evidence on the viruses found in the gastrointestinal tract, discussing
      their interactions with the resident bacterial microbiota and the host immune
      system, in order to explore the potential impact of the virome on human health. 

PMID- 25944981
TI  - Possible immunosuppressive effects of drug exposure and environmental and
      nutritional effects on infection and vaccination.
AB  - A variety of drugs which are not primarily considered to be immunosuppressive
      agents have been described to modulate the humoral and cellular immune response
      in humans or animals. Thereby they may have an influence on the effectiveness and
      possible side effects of vaccines. This mini review lists some of the different
      substance classes and also some of endogeneous, infectious, nutritional, and
      environmental influences with suspected capability to interfere with
      immunizations. Studies in most cases focused on substances with known
      immunosuppressive functions, but there is growing evidence for immunomodulatory
      effects also of commonly used drugs with wide distribution. In particular
      combinations of those antiproliferative and antiphlogistic side effects of
      different substance classes have not been studied in detail but may substantially
      interfere with the development of a functional humoral and cellular immune
      response. The drugs of importance include antipyretics, anticoagulants,
      tranquilizers, and substances influencing lipid metabolism but also commonly used
      drugs of abuse like alcohol or cannabinoids. Additional substances of
      environmental, nutritional, or microbiological origin may also play a role but
      their combinatory/synergistic effects have been disregarded so far due to the
      lack of systematic data and the complex study designs necessary to elucidate
      those complex epidemiologic questions. 

PMID- 25944982
TI  - Pathophysiological role of extracellular purinergic mediators in the control of
      intestinal inflammation.
AB  - Purinergic mediators such as adenosine 5'-triphosphate (ATP) are released into
      the extracellular compartment from damaged tissues and activated immune cells.
      They are then recognized by multiple purinergic P2X and P2Y receptors. Release
      and recognition of extracellular ATP are associated with both the development and
      the resolution of inflammation and infection. Accumulating evidence has recently
      suggested the potential of purinergic receptors as novel targets for drugs for
      treating intestinal disorders, including intestinal inflammation and irritable
      bowel syndrome. In this review, we highlight recent findings regarding the
      pathophysiological role of purinergic mediators in the development of intestinal
      inflammation. 

PMID- 25944983
TI  - Central role of gimap5 in maintaining peripheral tolerance and T cell homeostasis
      in the gut.
AB  - Inflammatory bowel disease (IBD) including Crohn's disease and ulcerative colitis
      is often precipitated by an abnormal immune response to microbiota due to host
      genetic aberrancies. Recent studies highlight the importance of the host genome
      and microflora interactions in the pathogenesis of mucosal inflammation including
      IBD. Specifically, genome-wide (GWAS) and also next-generation sequencing (NGS)
      including whole exome or genome sequencing-have uncovered a large number of
      susceptibility loci that predispose to autoimmune diseases and/or the two
      phenotypes of IBD. In addition, the generation of "IBD-prone" animal models using
      both reverse and forward genetic approaches has not only helped confirm the
      identification of susceptibility loci but also shed critical insight into the
      underlying molecular and cellular pathways that drive colitis development. In
      this review, we summarize recent findings derived from studies involving a novel
      early-onset model of colitis as it develops in GTPase of immunity-associated
      protein 5- (Gimap5-) deficient mice. In humans, GIMAP5 has been associated with
      autoimmune diseases although its function is poorly defined. Here, we discuss how
      defects in Gimap5 function impair immunological tolerance and lymphocyte survival
      and ultimately drive the development of CD4(+) T cell-mediated early-onset
      colitis. 

PMID- 25944984
TI  - Reduced systemic levels of IL-10 are associated with the severity of obstructive
      sleep apnea and insulin resistance in morbidly obese humans.
AB  - Obstructive sleep apnea (OSA) has been related to elevation of inflammatory
      cytokines and development of insulin resistance in morbidly obese (MO) subjects.
      However, it is still unclear whether the systemic concentration of anti
      inflammatory mediators is also affected in MO subjects directly related to the
      severity of OSA and level of insulin resistance. Normal weight and MO subjects
      were subjected to overnight polysomnography in order to establish the severity of
      OSA, according to the apnea-hypopnea index (AHI). Blood samples were obtained for
      estimation of total cholesterol and triglycerides, insulin, glucose, insulin
      resistance, tumor necrosis factor alpha (TNF-alpha), interleukin 12 (IL12), and
      interleukin 10 (IL-10). Serum levels of IL-10 were significantly lower in MO
      subjects with OSA than in MO and control individuals without OSA. Besides being
      inversely associated with serum TNF-alpha and IL-12, decreased IL-10 levels were
      significantly related to increased AHI, hyperinsulinemia, and insulin resistance.
      Serum IL-10 is significantly reduced in morbidly obese subjects with severe OSA
      while also showing a clear relationship with a state of hyperinsulinemia and
      insulin resistance probably regardless of obesity in the present sample. It may
      be of potential clinical interest to identify the stimulatory mechanisms of IL-10
      in obese individuals with OSA. 

PMID- 25944987
TI  - Oxidative stress in patients with Alzheimer's disease: effect of extracts of
      fermented papaya powder.
AB  - Brain tissue is particularly susceptible to oxidative stress (OS). Increased
      production of reactive oxygen species (ROS), reduced antioxidant systems, and
      decreased efficiency in repairing mechanisms have been linked to Alzheimer's
      disease (AD). Postmortem studies in AD patients' brains have shown oxidative
      damage markers (i.e., lipid peroxidation, protein oxidative damage, and
      glycoxidation). Fermented papaya (FPP, a product of Carica papaya Linn
      fermentation with yeast) is a nutraceutical supplement with favorable effects on
      immunological, hematological, inflammatory, and OS parameters in
      chronic/degenerative diseases. We studied 40 patients (age 78.2 +/- 1.1 years),
      28 AD patients, and 12 controls. Urinary 8-OHdG was measured to assess OS. Twenty
      AD patients were supplemented with FPP (Immunage, 4.5 grams/day) for 6 months,
      while controls did not receive any treatment. At baseline, 8-OHdG was
      significantly higher in patients with AD versus controls (13.7 +/- 1.61 ng/mL
      versus 1.6 +/- 0.12 ng/mL, P < 0.01). In AD patients FPP significantly decreased
      8-OHdG (14.1 +/- 1.7 ng/mL to 8.45 +/- 1.1 ng/mL, P < 0.01), with no significant
      changes in controls. AD is associated with increased OS, and FPP may be helpful
      to counteract excessive ROS in AD patients. 

PMID- 25944985
TI  - Inflammatory response mechanisms exacerbating hypoxemia in coexistent pulmonary
      fibrosis and sleep apnea.
AB  - Mediators of inflammation, oxidative stress, and chemoattractants drive the
      hypoxemic mechanisms that accompany pulmonary fibrosis. Patients with idiopathic
      pulmonary fibrosis commonly have obstructive sleep apnea, which potentiates the
      hypoxic stimuli for oxidative stress, culminating in systemic inflammation and
      generalized vascular endothelial damage. Comorbidities like pulmonary
      hypertension, obesity, gastroesophageal reflux disease, and hypoxic pulmonary
      vasoconstriction contribute to chronic hypoxemia leading to the release of
      proinflammatory cytokines that may propagate clinical deterioration and alter the
      pulmonary fibrotic pathway. Tissue inhibitor of metalloproteinase (TIMP-1),
      interleukin- (IL-) 1alpha, cytokine-induced neutrophil chemoattractant (CINC-1,
      CINC-2alpha/beta), lipopolysaccharide induced CXC chemokine (LIX), monokine
      induced by gamma interferon (MIG-1), macrophage inflammatory protein- (MIP-)
      1alpha, MIP-3alpha, and nuclear factor- (NF-) kappaB appear to mediate disease
      progression. Adipocytes may induce hypoxia inducible factor (HIF) 1alpha
      production; GERD is associated with increased levels of lactate dehydrogenase
      (LDH), alkaline phosphatase (ALP), and tumor necrosis factor alpha (TNF-alpha);
      pulmonary artery myocytes often exhibit increased cytosolic free Ca2+. Protein
      kinase C (PKC) mediated upregulation of TNF-alpha and IL-1beta also occurs in the
      pulmonary arteries. Increased understanding of the inflammatory mechanisms
      driving hypoxemia in pulmonary fibrosis and obstructive sleep apnea may
      potentiate the identification of appropriate therapeutic targets for developing
      effective therapies. 

PMID- 25944986
TI  - The impact of ATRA on shaping human myeloid cell responses to epithelial cell
      derived stimuli and on T-lymphocyte polarization.
AB  - Vitamin A plays an essential role in the maintenance of gut homeostasis but its
      interplay with chemokines has not been explored so far. Using an in vitro model
      system we studied the effects of human colonic epithelial cells (Caco2, HT-29,
      and HCT116) derived inflammatory stimuli on monocyte-derived dendritic cells and
      macrophages. Unstimulated Caco2 and HT-29 cells secreted CCL19, CCL21, and CCL22
      chemokines, which could attract dendritic cells and macrophages and induced CCR7
      receptor up-regulation by retinoic-acid resulting in dendritic cell migration.
      The chemokines Mk, CXCL16, and CXCL7 were secreted by all the 3 cell lines
      tested, and upon stimulation by IL-1beta or TNF-alpha this effect was inhibited
      by ATRA but had no impact on CXCL1, CXCL8, and CCL20 secretion in response to IL
      1beta. In the presence of ATRA the supernatants of these cells induced CD103
      expression on monocyte-derived dendritic cells and when conditioned by ATRA and
      cocultured with CD4(+) T-lymphocytes they reduced the proportion of Th17 T-cells.
      However, in the macrophage-T-cell cocultures the number of these effector T-cells
      was increased. Thus cytokine-activated colonic epithelial cells trigger the
      secretion of distinct combinations of chemokines depending on the proinflammatory
      stimulus and are controlled by retinoic acid, which also governs dendritic cell
      and macrophage responses. 

PMID- 25944988
TI  - HMGB-1 as a novel predictor of disease severity and prognosis in patients with
      hemorrhagic fever with renal syndrome.
AB  - OBJECTIVE: To examine the predictive capacity of the high mobility group box
      protein-1 (HMGB-1) for disease severity and prognosis of hemorrhagic fever with
      renal syndrome (HFRS). METHODS: One hundred and five HFRS patients and 28
      controls were studied. The concentrations of HMGB-1 in the blood were measured
      with a commercially available ELISA. The levels of white blood cells (WBC),
      platelets (PLT), hematocrit (HCT), albumin (ALB), blood urea nitrogen (BUN),
      serum creatinine (Scr), and uric acid (UA) were routinely tested in the same time
      frame. RESULTS: The levels of HMGB-1 increased with the severity of the disease
      (P < 0.001). HMGB-1 was positively correlated with WBC and BUN and negatively
      correlated with PLT, ALB, and UA (P < 0.001). HMGB-1 showed statistical
      significance for predicting prognosis (AUC = 0.800, P < 0.001). The sensitivity
      and specificity of HMGB-1, WBC, PLT, and ALB used in combination for predicting
      outcome were better than those of single analyses (AUC = 0.892, P < 0.001).
      CONCLUSIONS: HMGB-1 can be considered a novel biomarker for severity and outcome
      in patients with HFRS. The use of HMGB-1, WBC, PLT, and ALB in combination to
      predict the outcome in patients with HFRS exhibited an acceptable level of
      diagnostic capability.

PMID- 25944989
TI  - Epigenetic regulations of inflammatory cyclooxygenase-derived prostanoids:
      molecular basis and pathophysiological consequences.
AB  - The potential relevance of prostanoid signaling in immunity and immunological
      disorders, or disease susceptibility and individual variations in drug responses,
      is an important area for investigation. The deregulation of Cyclooxygenase- (COX
      ) derived prostanoids has been reported in several immunoinflammatory disorders
      such as asthma, rheumatoid arthritis, cancer, and autoimmune diseases. In
      addition to the environmental factors and the genetic background to diseases,
      epigenetic mechanisms involved in the fine regulation of prostanoid biosynthesis
      and/or receptor signaling appeared to be an additional level of complexity in the
      understanding of prostanoid biology and crucial in controlling the different
      components of the COX pathways. Epigenetic alterations targeting inflammatory
      components of prostanoid biosynthesis and signaling pathways may be important in
      the process of neoplasia, depending on the tissue microenvironment and target
      genes. Here, we focused on the epigenetic modifications of inflammatory
      prostanoids in physiological immune response and immunological disorders. We
      described how major prostanoids and their receptors can be functionally regulated
      epigenetically and consequently the impact of these processes in the pathogenesis
      inflammatory diseases and the development of therapeutic approaches that may have
      important clinical applications. 

PMID- 25944990
TI  - Withdrawal of anti-tumour necrosis factor alpha therapy in inflammatory bowel
      disease.
AB  - Anti-tumour necrosis factor alpha (anti-TNFalpha) therapy is an established
      treatment in inflammatory bowel disease. However, this treatment is associated
      with high costs and the possibility of severe adverse events representing a true
      challenge for patients, clinicians and health care systems. Consequently, a
      crucial question is raised namely if therapy can be stopped once remission is
      achieved and if so, how and in whom. Additionally, in a real-life clinical
      setting, discontinuation may also be considered for other reasons such as the
      patient's preference, pregnancy, social reasons as moving to countries or
      continents with less access, or different local policy or reimbursement. In
      contrast to initiation of anti-TNFalpha therapy guidelines regarding stopping of
      this treatment are missing. As a result, the decision of discontinuation is still
      a challenging aspect in the use of anti-TNFalpha therapy. Currently this is
      typically based on an estimated, case-by-case, benefit-risk ratio. This editorial
      is intended to provide an overview of recent data on this topic and shed light on
      the proposed drug withdrawal strategies. 

PMID- 25944991
TI  - Challenges in animal modelling of mesenchymal stromal cell therapy for
      inflammatory bowel disease.
AB  - Utilization of mesenchymal stromal cells (MSCs) for the treatment of Crohn's
      disease and ulcerative colitis is of translational interest. Safety of MSC
      therapy has been well demonstrated in early phase clinical trials but efficacy in
      randomized clinical trials needs to be demonstrated. Understanding MSC mechanisms
      of action to reduce gut injury and inflammation is necessary to improve current
      ongoing and future clinical trials. However, two major hurdles impede the direct
      translation of data derived from animal experiments to the clinical situation:
      (1) limitations of the currently available animal models of colitis that reflect
      human inflammatory bowel diseases (IBD). The etiology and progression of human
      IBD are multifactorial and hence a challenge to mimic in animal models; and (2)
      Species specific differences in the functionality of MSCs derived from mice
      versus humans. MSCs derived from mice and humans are not identical in their
      mechanisms of action in suppressing inflammation. Thus, preclinical animal
      studies with murine derived MSCs cannot be considered as an exact replica of
      human MSC based clinical trials. In the present review, we discuss the
      therapeutic properties of MSCs in preclinical and clinical studies of IBD. We
      also discuss the challenges and approaches of using appropriate animal models of
      colitis, not only to study putative MSC therapeutic efficacy and their mechanisms
      of action, but also the suitability of translating findings derived from such
      studies to the clinic. 

PMID- 25944992
TI  - Metastatic pancreatic cancer: Is there a light at the end of the tunnel?
AB  - Due to extremely poor prognosis, pancreatic cancer (PDAC) represents the fourth
      leading cause of cancer-related death in Western countries. For more than a
      decade, gemcitabine (Gem) has been the mainstay of first-line PDAC treatment.
      Many efforts aimed at improving single-agent Gem efficacy by either combining it
      with a second cytotoxic/molecularly targeted agent or pharmacokinetic modulation
      provided disappointing results. Recently, the field of systemic therapy of
      advanced PDAC is finally moving forward. Polychemotherapy has shown promise over
      single-agent Gem: regimens like PEFG-PEXG-PDXG and GTX provide significant
      potential advantages in terms of survival and/or disease control, although
      sometimes at the cost of poor tolerability. The PRODIGE 4/ACCORD 11 was the first
      phase III trial to provide unequivocal benefit using the polychemotherapy regimen
      FOLFIRINOX; however the less favorable safety profile and the characteristics of
      the enrolled population, restrict the use of FOLFIRINOX to young and fit PDAC
      patients. The nanoparticle albumin-bound paclitaxel (nab-Paclitaxel) formulation
      was developed to overcome resistance due to the desmoplastic stroma surrounding
      pancreatic cancer cells. Regardless of whether or not this is its main mechanisms
      of action, the combination of nab-Paclitaxel plus Gem showed a statistically and
      clinically significant survival advantage over single agent Gem and significantly
      improved all the secondary endpoints. Furthermore, recent findings on maintenance
      therapy are opening up potential new avenues in the treatment of advanced PDAC,
      particularly in a new era in which highly effective first-line regimens allow
      patients to experience prolonged disease control. Here, we provide an overview of
      recent advances in the systemic treatment of advanced PDAC, mostly focusing on
      recent findings that have set new standards in metastatic disease. Potential
      avenues for further development in the metastatic setting and current efforts to
      integrate new effective chemotherapy regimens in earlier stages of disease
      (neoadjuvant, adjuvant, and multimodal approaches in both resectable and
      unresectable patients) are also briefly discussed. 

PMID- 25944993
TI  - Vanek's tumor of the small bowel in adults.
AB  - Inflammatory fibroid polyps (IFPs), or Vanek's tumor, are one of the least common
      benign small bowel tumors. IFP affects both sexes and all age groups, with a peak
      of incidence in the fifth and seventh decades. They can be found throughout the
      gastrointestinal tract but most commonly in the gastric antrum or ileum. The
      underlying cause of IFPs is still unknown. Genetic study of IFP showed mutations
      in platelet derived growth factor alpha in some cases. At the time of diagnosis
      most IFPs have a diameter of 3 to 4 cm. The lesions have always been recorded as
      solitary polyps. Symptoms depend on the location and the size of the lesion,
      including abdominal pain, vomiting, altered small bowel movements,
      gastrointestinal bleeding and loss of weight. IFPs arising below the Treitz
      ligament can present with an acute abdomen, usually due to intussusceptions.
      Abdominal computed tomography is currently considered the most sensitive
      radiological method to show the polyp or to confirm intussusceptions. Most
      inflammatory fibroid polyps can be removed by endoscopy. Surgery is rarely
      needed. Exploratory laparoscopy or laparotomy is frequently recommended as the
      best treatment for intussusceptions caused by IFP. The operation should be
      performed as early as possible in order to prevent the intussusceptions from
      leading to ischemia, necrosis and subsequent perforation of the invaginated bowel
      segment. This report aims at reviewing the diagnosis, etiology, genetics,
      clinical presentation, endoscopy, radiology, and best treatment of IFP. 

PMID- 25944994
TI  - New endoscopic ultrasound techniques for digestive tract diseases: A
      comprehensive review.
AB  - Endoscopic ultrasound (EUS) is one of the most important modalities for the
      diagnosis of digestive tract diseases. EUS has been evolving ever since it was
      introduced. New techniques such as elastography and contrast enhancement have
      emerged, increasing the accuracy, sensitivity and specificity of EUS for the
      diagnosis of digestive tract diseases including pancreatic masses and
      lymphadenopathy. EUS-elastography evaluates tissue elasticity and therefore, can
      be used to differentiate various lesions. Contrast-enhanced EUS can distinguish
      benign from malignant pancreatic lesions and lymphadenopathy using the
      intravenous injection of contrast agents. This review discusses the principles
      and types of these new techniques, as well as their clinical applications and
      limitations. 

PMID- 25944995
TI  - Murine study of portal hypertension associated endothelin-1 hypo-response.
AB  - AIM: To investigate endothelin-1 hypo-responsive associated with portal
      hypertension in order to improve patient treatment outcomes. METHODS: Wild type,
      eNOS(-/-) and iNOS(-/-) mice received partial portal vein ligation surgery to
      induce portal hypertension or sham surgery. Development of portal hypertension
      was determined by measuring the splenic pulp pressure, abdominal aortic flow and
      portal systemic shunting. To measure splenic pulp pressure, a microtip pressure
      transducer was inserted into the spleen pulp. Abdominal aortic flow was measured
      by placing an ultrasonic Doppler flow probe around the abdominal aorta between
      the diaphragm and celiac artery. Portal systemic shunting was calculated by
      injection of fluorescent microspheres in to the splenic vein and determining the
      percentage accumulation of spheres in liver and pulmonary beds. Endothelin-1 hypo
      response was evaluated by measuring the change in abdominal aortic flow in
      response to endothelin-1 intravenous administration. In addition, thoracic aorta
      endothelin-1 contraction was measured in 5 mm isolated thoracic aorta rings ex
      vivo using an ADI small vessel myograph. RESULTS: In wild type and iNOS(-/-) mice
      splenic pulp pressure increased from 7.5 +/- 1.1 mmHg and 7.2 +/- 1 mmHg to 25.4
      +/- 3.1 mmHg and 22 +/- 4 mmHg respectively. In eNOS(-/-) mice splenic pulp
      pressure was increased after 1 d (P = NS), after which it decreased and by 7 d
      was not significantly elevated when compared to 7 d sham operated controls (6.9
      +/- 0.6 mmHg and 7.3 +/- 0.8 mmHg respectively, P = 0.3). Abdominal aortic flow
      was increased by 80% and 73% in 7 d portal vein ligated wild type and iNOS when
      compared to shams, whereas there was no significant difference in 7 d portal vein
      ligated eNOS(-/-) mice when compared to shams. Endothelin-1 induced a rapid
      reduction in abdominal aortic blood flow in wild type, eNOS(-/-) and iNOS(-/-)
      sham mice (50% +/- 8%, 73% +/- 9% and 47% +/- 9% respectively). Following portal
      vein ligation endothelin-1 reduction in blood flow was significantly diminished
      in each mouse group. Abdominal aortic flow was reduced by 19% +/- 9%, 32% +/- 10%
      and 9% +/- 9% in wild type, eNOS(-/-) and iNOS(-/-) mice respectively.
      CONCLUSION: Aberrant endothelin-1 response in murine portal hypertension is NOS
      isoform independent. Moreover, portal hypertension in the portal vein ligation
      model is independent of ET-1 function.

PMID- 25944996
TI  - Toxoplasma gondii causes death and plastic alteration in the jejunal myenteric
      plexus.
AB  - AIM: To assess the effects of ME-49 Toxoplasma gondii (T. gondii) strain
      infection on the myenteric plexus and external muscle of the jejunum in rats.
      METHODS: Thirty rats were distributed into two groups: the control group (CG) (n
      = 15) received 1 mL of saline solution orally, and the infected group (IG) (n =
      15) inoculated with 1 mL of saline solution containing 500 oocysts of M-49 T.
      gondii strain orally. After 36 d of infection, the rats were euthanized.
      Infection with T. gondii was confirmed by blood samples collected from all rats
      at the beginning and end of the experiment. The jejunum of five animals was
      removed and submitted to routine histological processing (paraffin) for analysis
      of external muscle thickness. The remaining jejunum from the others animals was
      used to analyze the general population and the NADH-diaphorase, VIPergic and
      nitrergic subpopulations of myenteric neurons; and the enteric glial cells (S100
      IR). RESULTS: Serological analysis showed that animals from the IG were infected
      with the parasite. Hypertrophy affecting jejunal muscle thickness was observed in
      the IG rats (77.02 +/- 42.71) in relation to the CG (51.40 +/- 12.34), P < 0.05.
      In addition, 31.2% of the total number of myenteric neurons died (CG: 39839.3 +/-
      5362.3; IG: 26766.6 +/- 2177.6; P < 0.05); hyperplasia of nitrergic myenteric
      neurons was observed (CG: 7959.0 +/- 1290.4; IG: 10893.0 +/- 1156.3; P < 0.05);
      general hypertrophy of the cell body in the remaining myenteric neurons was noted
      [CG: 232.5 (187.2-286.0); IG: 248.2 (204.4-293.0); P < 0.05]; hypertrophy of the
      smallest varicosities containing VIP neurotransmitter was seen (CG: 0.46 +/-
      0.10; IG: 0.80 +/- 0.16; P < 0.05) and a reduction of 25.3% in enteric glia cells
      (CG: 12.64 +/- 1.27; IG: 10.09 +/- 2.10; P < 0.05) was observed in the infected
      rats. CONCLUSION: It was concluded that infection with oocysts of ME-49 T. gondii
      strain caused quantitative and plastic alterations in the myenteric plexus of the
      jejunum in rats.

PMID- 25944997
TI  - Hydrogen sulfide-induced enhancement of gastric fundus smooth muscle tone is
      mediated by voltage-dependent potassium and calcium channels in mice.
AB  - AIM: To investigate the effect of hydrogen sulfide (H2S) on smooth muscle
      motility in the gastric fundus. METHODS: The expression of cystathionine beta
      synthase (CBS) and cystathionine gamma-lyase (CSE) in cultured smooth muscle
      cells from the gastric fundus was examined by the immunocytochemistry technique.
      The tension of the gastric fundus smooth muscle was recorded by an isometric
      force transducer under the condition of isometric contraction with each end of
      the smooth muscle strip tied with a silk thread. Intracellular recording was used
      to identify whether hydrogen sulfide affects the resting membrane potential of
      the gastric fundus in vitro. Cells were freshly separated from the gastric fundus
      of mice using a variety of enzyme digestion methods and whole-cell patch-clamp
      technique was used to find the effects of hydrogen sulfide on voltage-dependent
      potassium channel and calcium channel. Calcium imaging with fura-3AM loading was
      used to investigate the mechanism by which hydrogen sulfide regulates gastric
      fundus motility in cultured smooth muscle cells. RESULTS: We found that both CBS
      and CSE were expressed in the cultured smooth muscle cells from the gastric
      fundus and that H2S increased the smooth muscle tension of the gastric fundus in
      mice at low concentrations. In addition, nicardipine and aminooxyacetic acid
      (AOAA), a CBS inhibitor, reduced the tension, whereas Nomega-nitro-L-arginine
      methyl ester, a nonspecific nitric oxide synthase, increased the tension. The
      AOAA-induced relaxation was significantly recovered by H2S, and the NaHS-induced
      increase in tonic contraction was blocked by 5 mmol/L 4-aminopyridine and 1
      MUmol/L nicardipine. NaHS significantly depolarized the membrane potential and
      inhibited the voltage-dependent potassium currents. Moreover, NaHS increased L
      type Ca(2+) currents and caused an elevation in intracellular calcium
      ([Ca(2+)]i). CONCLUSION: These findings suggest that H2S may be an excitatory
      modulator in the gastric fundus in mice. The excitatory effect is mediated by
      voltage-dependent potassium and L-type calcium channels.

PMID- 25944998
TI  - Alterations in serotonin, transient receptor potential channels and protease
      activated receptors in rats with irritable bowel syndrome attenuated by Shugan
      decoction.
AB  - AIM: To determine the molecular mechanisms of Shugan decoction (SGD) in the
      regulation of colonic motility and visceral hyperalgesia (VHL) in irritable bowel
      syndrome (IBS). METHODS: The chemical compounds contained in SGD were measured by
      high-performance liquid chromatography. A rat model of IBS was induced by chronic
      water avoidance stress (WAS). The number of fecal pellets was counted after WAS
      and the pain pressure threshold was measured by colorectal distension.
      Morphological changes in colonic mucosa were detected by hematoxylin-eosin
      staining. The contents of tumor necrosis factor (TNF)-alpha in colonic tissue and
      calcitonin-gene-related peptide (CGRP) in serum were measured by ELISA. The
      protein expression of serotonin [5-hydroxytryptamide (5-HT)], serotonin
      transporter (SERT), chromogranin A (CgA) and CGRP in colon tissue was measured by
      immunohistochemistry. RESULTS: SGD inhibited colonic motility dysfunction and VHL
      in rats with IBS. Blockers of transient receptor potential (TRP) vanilloid 1
      (TRPV1) (Ruthenium Red) and TRP ankyrin-1 (TRPA1) (HC-030031) and activator of
      protease-activated receptor (PAR)4 increased the pain pressure threshold, whereas
      activators of PAR2 and TRPV4 decreased the pain pressure threshold in rats with
      IBS. The effect of SGD on pain pressure threshold in these rats was abolished by
      activators of TRPV1 (capsaicin), TRPV4 (RN1747), TRPA1 (Polygodial) and PAR2
      (AC55541). In addition, CGRP levels in serum and colonic tissue were both
      increased in these rats. TNF-alpha level in colonic tissue was also significantly
      upregulated. However, the levels of 5-HT, SERT and CgA in colonic tissue were
      decreased. All these pathological changes in rats with IBS were attenuated by
      SGD. CONCLUSION: SGD alleviated VHL and attenuated colon motility in IBS, partly
      by regulating TRPV1, TRPV4, TRPA1, PAR2, 5-HT, CgA and SERT, and reducing CGRP
      and TNF-alpha level.

PMID- 25945000
TI  - Comparison of two different laparotomy methods for modeling rabbit VX2
      hepatocarcinoma.
AB  - AIM: To compare two different laparotomy methods for modeling rabbit VX2
      hepatocarcinoma. METHODS: Thirty New Zealand rabbits were randomly divided into
      two groups: A and B. Group A was assigned a traditional laparotomy method
      (embedding tumor fragments directly into the liver with tweezers). Group B was
      subjected to an improved laparotomy method (injection of tumor fragments into the
      liver through a 15 G syringe needle). The operation time, incision length,
      incision infection rate, and mortality rate were compared between the two groups
      after laparotomy. Magnetic resonance imaging (MRI) was performed to evaluate
      tumor formation rates and the characteristics of the tumors 2 wk after
      laparotomy. RESULTS: The mean operation times for the two groups (Group A vs
      Group B) were 23.2 +/- 3.4 min vs 17.5 +/- 2.9 min (P < 0.05); the incision
      length was 3.3 +/- 0.5 cm vs 2.4 +/- 0.6 cm (P < 0.05); and the mortality rate
      after 2 wk was 26.7% vs 0% (P < 0.05); all of these outcomes were significantly
      different between the two groups. The incision infection rates in the two groups
      were 6.7% vs 0% (P > 0.05), which were not significantly different. MRI performed
      after 2 weeks showed that the tumor formation rates in the two groups were 90.9%
      vs 93.3% (P > 0.05). These rates were not significantly different between the two
      groups. The celiac implantation rate and abdominal wall metastasis rate in the
      two groups were 36.4% vs 13.3% (P < 0.05) and 27.2% vs 6.7% (P < 0.05),
      respectively, which were significantly different between the two groups.
      CONCLUSION: The tumor formation rates were not significantly different between
      the two methods for modeling rabbit VX2 hepatocarcinoma. However, the improved
      method is recommended because it has certain advantages.

PMID- 25944999
TI  - Inflammatory microenvironment and expression of chemokines in hepatocellular
      carcinoma.
AB  - AIM: To study the inflammatory microenvironment and expression of chemokines in
      hepatocellular carcinoma (HCC) in nude mice. METHODS: CBRH-7919 HCC cells were
      injected into the subcutaneous region of nude mice. Beginning two weeks after the
      challenge, tumor growth was measured every week for six weeks. The stromal
      microenvironment and inflammatory cell infiltration was assessed by
      immunohistochemistry in paired tumor and adjacent peritumoral samples, and
      macrophage phenotype was assessed using double-stain immunohistochemistry
      incorporating expression of an intracellular enzyme. A chemokine PCR array,
      comprised of 98 genes, was used to screen differential gene expressions, which
      were validated by Western blotting. Additionally, expression of identified
      chemokines was knocked-down by RNA interference, and the effect on tumor growth
      was assessed. RESULTS: Inflammatory cell infiltrates are a key feature of
      adjacent peritumoral tissues with increased macrophage, neutrophil, and T cell
      (specifically helper and activated subsets) infiltration. Macrophages within
      adjacent peritumoral tissues express inducible nitric oxide synthase, suggestive
      of a proinflammatory phenotype. Fifty-one genes were identified in tumor tissues
      during the progression period, including 50 that were overexpressed (including
      CXCL1, CXCL2 and CXCL3) and three that were underexpressed (CXCR1, Ifg and Actb).
      RNA interference of CXCL1 in the CBRH-7919 cells decreased the growth of tumors
      in nude mice and inhibited expression of CXCL2, CXCL3 and interleukin-1beta
      protein. CONCLUSION: These findings suggest that CXCL1 plays a critical role in
      tumor growth and may serve as a potential molecular target for use in HCC
      therapy.

PMID- 25945001
TI  - Intestinal dendritic cells change in number in fulminant hepatic failure.
AB  - AIM: To investigate the change in intestinal dendritic cell (DC) number in
      fulminant hepatic failure (FHF). METHODS: An animal model of FHF was created.
      Intestinal CD11b/c was detected by immunohistochemistry and Western blot.
      Quantitative real-time polymerase chain reaction (PCR) was used to detect
      intestinal integrin-alpha mRNA expression. Intestinal CD83, CD86, CD74, CD3 and
      AKT were detected by immunohistochemistry, Western blot and PCR. Phosphorylated
      AKT (p-AKT) was detected by immunohistochemistry and Western blot. RESULTS: In
      the FHF group [D-galactosamine (D-Galn) + lipopolysaccharide (LPS) group], the
      mice began to die after 6 h; conversely, in the D-Galn and LPS groups, the
      activity of mice was poor, but there were no deaths. Immunohistochemistry results
      showed that in FHF, the expression of CD11b/c (7988400 +/- 385941 vs 1102400 +/-
      132273, P < 0.05), CD83 (13875000 +/- 467493 vs 9257600 +/- 400364, P < 0.05),
      CD86 (7988400 +/- 385941 vs 1102400 +/- 13227, P < 0.05) and CD74 (11056000 +/-
      431427 vs 4633400 +/- 267903, P < 0.05) was significantly increased compared with
      the normal saline (NS) group. Compared with the NS group, the protein expression
      of CD11b/c (5.4817 +/- 0.77 vs 1.4073 +/- 0.37, P < 0.05) and CD86 (4.2673 +/-
      0.69 vs 1.1379 +/- 0.42, P < 0.05) was significantly increased. Itg-alpha (1.1224
      +/- 0.3 vs 0.4907 +/- 0.19, P < 0.05), CD83 (3.6986 +/- 0.40 vs 1.0762 +/- 0.22,
      P < 0.05) and CD86 (1.5801 +/- 0.32 vs 0.8846 +/- 0.10, P < 0.05) mRNA expression
      was increased significantly in the FHF group. At the protein level, expression of
      CD74 in the FHF group (2.3513 +/- 0.52) was significantly increased compared with
      the NS group (1.1298 +/- 0.33), whereas in the LPS group (2.3891 +/- 0.47), the
      level of CD74 was the highest (P < 0.05). At the gene level, the relative
      expression of CD74 mRNA in the FHF group (1.5383 +/- 0.26) was also significantly
      increased in comparison to the NS group (0.7648 +/- 0.22; P < 0.05). CD3
      expression was the highest in the FHF group (P < 0.05). In the FHF, LPS and D
      Galn groups, the expression of AKT at the protein and mRNA levels was elevated
      compared with the NS group, but there was no statistical significance (P > 0.05).
      The p-AKT protein expression in the FHF (1.54 +/- 0.06), LPS (1.56 +/- 0.05) and
      D-Galn (1.29 +/- 0.03) groups was higher than that in the NS group (1.07 +/-
      0.03) (P < 0.05). CONCLUSION: In FHF, a large number of DCs mature, express CD86,
      and activate MHC class II molecular pathways to induce a T cell response, and the
      AKT pathway is activated.

PMID- 25945002
TI  - Estimating steatosis and fibrosis: Comparison of acoustic structure
      quantification with established techniques.
AB  - AIM: To compare ultrasound-based acoustic structure quantification (ASQ) with
      established non-invasive techniques for grading and staging fatty liver disease.
      METHODS: Type 2 diabetic patients at risk of non-alcoholic fatty liver disease (n
      = 50) and healthy volunteers (n = 20) were evaluated using laboratory analysis
      and anthropometric measurements, transient elastography (TE), controlled
      attenuation parameter (CAP), proton magnetic resonance spectroscopy ((1)H-MRS;
      only available for the diabetic cohort), and ASQ. ASQ parameters mode, average
      and focal disturbance (FD) ratio were compared with: (1) the extent of liver
      fibrosis estimated from TE and non-alcoholic fatty liver disease (NAFLD) fibrosis
      scores; and (2) the amount of steatosis, which was classified according to CAP
      values. RESULTS: Forty-seven diabetic patients (age 67.0 +/- 8.6 years; body mass
      index 29.4 +/- 4.5 kg/m2) with reliable CAP measurements and all controls (age
      26.5 +/- 3.2 years; body mass index 22.0 +/- 2.7 kg/m2) were included in the
      analysis. All ASQ parameters showed differences between healthy controls and
      diabetic patients (P < 0.001, respectively). The ASQ FD ratio (logarithmic)
      correlated with the CAP (r = -0.81, P < 0.001) and (1)H-MRS (r = -0.43, P =
      0.004) results. The FD ratio [CAP < 250 dB/m: 107 (102-109), CAP between 250 and
      300 dB/m: 106 (102-114); CAP between 300 and 350 dB/m: 105 (100-112), CAP >= 350
      dB/m: 102 (99-108)] as well as mode and average parameters, were reduced in cases
      with advanced steatosis (ANOVA P < 0.05). However, none of the ASQ parameters
      showed a significant difference in patients with advanced fibrosis, as determined
      by TE and the NAFLD fibrosis score (P > 0.08, respectively). CONCLUSION: ASQ
      parameters correlate with steatosis, but not with fibrosis in fatty liver
      disease. Steatosis estimation with ASQ should be further evaluated in biopsy
      controlled studies.

PMID- 25945003
TI  - Clinical impact of endoscopy position detecting unit (UPD-3) for a non-sedated
      colonoscopy.
AB  - AIM: To evaluate whether an endoscopy position detecting unit (UPD-3) can improve
      cecal intubation rates, cecal intubation times and visual analog scale (VAS) pain
      scores, regardless of the colonoscopist's level of experience. METHODS: A total
      of 260 patients (170 men and 90 women) who underwent a colonoscopy were divided
      into the UPD-3-guided group or the conventional group (no UPD-3 guidance).
      Colonoscopies were performed by experts (experience of more than 1000
      colonoscopies) or trainees (experience of less than 100 colonoscopies). Cecal
      intubation rates, cecal intubation times, insertion methods (straight insertion:
      shortening the colonic fold through the bending technique; roping insertion:
      right turn shortening technique) and patient discomfort were assessed. Patient
      discomfort during the endoscope insertion was scored by the VAS that was divided
      into 6 degrees of pain. RESULTS: The cecum intubation rates, cecal intubation
      times, number of cecal intubations that were performed in < 15 min and insertion
      methods were not significantly different between the conventional group and the
      UPD-3-guided group. The number of patients who experienced pain during the
      insertion was markedly less in the UPD-3-guided group than in the conventional
      group. Univariate and multivariate analysis showed that the following factors
      were associated with lower VAS pain scores during endoscope insertion: insertion
      method (straight insertion) and UPD-3 guidance in the trainee group. For the
      experts group, univariate analysis showed that only the insertion method
      (straight insertion) was associated with lower VAS pain scores. CONCLUSION:
      Although UPD-3 guidance did not shorten intubation times, it resulted in less
      patient pain during endoscope insertion compared with conventional endoscopy for
      the procedures performed by trainees.

PMID- 25945004
TI  - Palliative chemotherapy for gastroesophageal cancer in old and very old patients:
      A retrospective cohort study at the National Center for Tumor Diseases,
      Heidelberg.
AB  - AIM: To investigate the outcome of palliative chemotherapy in old patients with
      gastroesophageal cancer at the National Center for Tumor Diseases, Heidelberg.
      METHODS: Using a prospectively generated database, we retrospectively analyzed 55
      patients >= 70 years under palliative chemotherapy for advanced gastroesophageal
      cancer at the outpatient clinic of the National Center for Tumor Diseases
      Heidelberg, Germany between January 2006 and December 2013. Further requirements
      for inclusion were (1) histologically proven diagnosis of gastroesophageal
      cancer; (2) advanced (metastatic or inoperable) disease; and (3) no history of
      radiation or radiochemotherapy. The clinical information included Eastern
      Cooperative Oncology Group performance status (ECOG PS), presence and site of
      metastases at diagnosis, date of previous surgery and perioperative chemotherapy,
      start and stop date of first-line treatment, toxicities and consecutive dosage
      reductions of first-line treatment, response to first-line therapy, date of
      progression, usage of second-line therapies and date and cause of death. Survival
      times [progression-free survival (PFS), overall survival (OS) and residual
      survival (RS)] were calculated. Toxicity and safety were examined. Prognostic
      factors including ECOG PS, age and previous perioperative treatment were
      analyzed. RESULTS: Median age of our cohort was 76 years. 86% of patients
      received a combination of two cytotoxic drugs. 76 percent of patients had an
      oxaliplatin-based first-line therapy with the oxaliplatin and 5-fluorouracil
      regimen being the predominantely chosen regimen (69%). Drug modifications due to
      toxicity were necessary in 56% of patients, and 11% of patients stopped treatment
      due to toxicities. Survival times of our cohort are in good accordance with the
      major phase III trials that included mostly younger patients: PFS and OS were 5.8
      and 9.5 mo, respectively. Survival differed significantly between patient groups
      with low (<= 1) and high (>= 2) ECOG PS (12.7 mo vs 3.8 mo, P < 0.001). Very old
      patients (>= 75 years) did not show a worse outcome in terms of survival.
      Patients receiving second-line treatment (51%) had a significantly longer RS than
      patients with best supportive care (6.8 vs 1.4 mo, P = 0.001). Initial ECOG PS
      was a strong prognostic factor for PFS, OS and RS. CONCLUSION: Old patients with
      non-curable gastroesophageal cancer should be offered chemotherapy, and ECOG PS
      is a tool for balancing benefit and harm upfront. Second-line treatment is
      reasonable.

PMID- 25945005
TI  - Proton-pump inhibitors for prevention of upper gastrointestinal bleeding in
      patients undergoing dialysis.
AB  - AIM: To investigate the preventive effects of low-dose proton-pump inhibitors
      (PPIs) for upper gastrointestinal bleeding (UGIB) in end-stage renal disease.
      METHODS: This was a retrospective cohort study that reviewed 544 patients with
      end-stage renal disease who started dialysis at our center between 2005 and 2013.
      We examined the incidence of UGIB in 175 patients treated with low-dose PPIs and
      369 patients not treated with PPIs (control group). RESULTS: During the study
      period, 41 patients developed UGIB, a rate of 14.4/1000 person-years. The mean
      time between the start of dialysis and UGIB events was 26.3 +/- 29.6 mo. Bleeding
      occurred in only two patients in the PPI group (2.5/1000 person-years) and in 39
      patients in the control group (19.2/1000 person-years). Kaplan-Meier analysis of
      cumulative non-bleeding survival showed that the probability of UGIB was
      significantly lower in the PPI group than in the control group (log-rank test, P
      < 0.001). Univariate analysis showed that coronary artery disease, PPI use, anti
      coagulation, and anti-platelet therapy were associated with UGIB. After
      adjustments for the potential factors influencing risk of UGIB, PPI use was shown
      to be significantly beneficial in reducing UGIB compared to the control group (HR
      = 13.7, 95%CI: 1.8-101.6; P = 0.011). CONCLUSION: The use of low-dose PPIs in
      patients with end-stage renal disease is associated with a low frequency of UGIB.

PMID- 25945006
TI  - Hepatobiliary complications of alveolar echinococcosis: A long-term follow-up
      study.
AB  - AIM: To determine the long-term hepatobiliary complications of alveolar
      echinococcosis (AE) and treatment options using interventional methods. METHODS:
      Included in the study were 35 patients with AE enrolled in the Echinococcus
      Multilocularis Data Bank of the University Hospital of Ulm. Patients underwent
      endoscopic intervention for treatment of hepatobiliary complications between 1979
      and 2012. Patients' epidemiologic data, clinical symptoms, and indications for
      the intervention, the type of intervention and any additional procedures, hepatic
      laboratory parameters (pre- and post-intervention), medication and surgical
      treatment (pre- and post-intervention), as well as complications associated with
      the intervention and patients' subsequent clinical courses were analyzed. In
      order to compare patients with AE with and without history of intervention, data
      from an additional 322 patients with AE who had not experienced hepatobiliary
      complications and had not undergone endoscopic intervention were retrieved and
      analyzed. RESULTS: Included in the study were 22 male and 13 female patients
      whose average age at first diagnosis was 48.1 years and 52.7 years at the time of
      intervention. The average time elapsed between first diagnosis and onset of
      hepatobiliary complications was 3.7 years. The most common symptoms were
      jaundice, abdominal pains, and weight loss. The number of interventions per
      patient ranged from one to ten. Endoscopic retrograde cholangiopancreatography
      (ERCP) was most frequently performed in combination with stent placement (82.9%),
      followed by percutaneous transhepatic cholangiodrainage (31.4%) and ERCP without
      stent placement (22.9%). In 14.3% of cases, magnetic resonance
      cholangiopancreatography was performed. A total of eight patients received a
      biliary stent. A comparison of biochemical hepatic function parameters at first
      diagnosis between patients who had or had not undergone intervention revealed
      that these were significantly elevated in six patients who had undergone
      intervention. Complications (cholangitis, pancreatitis) occurred in six patients
      during and in 12 patients following the intervention. The average survival
      following onset of hepatobiliary complications was 8.8 years. CONCLUSION:
      Hepatobiliary complications occur in about 10% of patients. A significant
      increase in hepatic transaminase concentrations facilitates the diagnosis.
      Interventional methods represent viable management options.

PMID- 25945007
TI  - Prognostic roles of preoperative alpha-fetoprotein and des-gamma-carboxy
      prothrombin in hepatocellular carcinoma patients.
AB  - AIM: To clarify the utility of using des-gamma-carboxy prothrombin (DCP) and
      alpha-fetoprotein (AFP) levels to predict the prognosis of hepatocellular
      carcinoma (HCC) in patients with hepatitis B virus (HBV) and the hepatitis C
      virus (HCV) infections. METHODS: A total of 205 patients with HCC (105 patients
      with HBV infection 100 patients with HCV infection) who underwent primary
      hepatectomy between January 2004 and May 2012 were enrolled retrospectively.
      Preoperative AFP and DCP levels were used to create interactive dot diagrams to
      predict recurrence within 2 years after hepatectomy, and cutoff levels were
      calculated. Patients in the HBV and HCV groups were classified into three groups:
      a group with low AFP and DCP levels (LL group), a group in which one of the two
      parameters was high and the other was low (HL group), and a group with high AFP
      and DCP levels (HH group). Liver function parameters, the postoperative
      recurrence-free survival rate, and postoperative overall survival were compared
      between groups. The survival curves were compared by log-rank test using the
      Kaplan-Meier method. Multivariate analysis using a Cox forward stepwise logistic
      regression model was conducted for a prognosis. RESULTS: The preoperative AFP
      cutoff levels for recurrence within 2 years after hepatectomy in the HBV and HCV
      groups were 529.8 ng/mL and 60 mAU/mL, respectively; for preoperative DCP levels,
      the cutoff levels were 21.0 ng/mL in the HBV group and 67 mAU/mL in the HCV
      group. The HBV group was significantly different from the other groups in terms
      of vascular invasion, major hepatectomy, volume of intraoperative blood loss, and
      surgical duration. Significant differences were found between the LL group, the
      HL group, and the HH group in terms of both mean disease-free survival time
      (MDFST) and mean overall survival time (MOST): 64.81 +/- 7.47 vs 36.63 +/- 7.62
      vs 18.98 +/- 6.17 mo (P = 0.001) and 85.30 +/- 6.55 vs 59.44 +/- 7.87 vs 46.57 +/
      11.20 mo (P = 0.018). In contrast, the HCV group exhibited a significant
      difference in tumor size, vascular invasion, volume of intraoperative blood loss,
      and surgical duration; however, no significant difference was observed between
      the three groups in liver function parameters except for albumin levels. In the
      LL group, the HL group, and the HH group, the MDFST was 50.09 +/- 5.90, 31.01 +/-
      7.21, and 14.81 +/- 3.08 mo (log-rank test, P < 0.001), respectively, and the
      MOST was 79.45 +/- 8.30, 58.82 +/- 7.56, and 32.87 +/- 6.31 mo (log-rank test, P
      < 0.001), respectively. CONCLUSION: In the HBV group, the prognosis was poor when
      either AFP or DCP levels were high. In the HCV group, the prognosis was good when
      either or both levels were low; however, the prognosis was poor when both levels
      were high. High levels of both AFP and DCP were an independent risk factor
      associated with tumor recurrence in the HBV and HCV groups. The relationship
      between tumor marker levels and prognosis was characteristic to the type of viral
      hepatitis.

PMID- 25945008
TI  - Biliary drainage strategy of unresectable malignant hilar strictures by computed
      tomography volumetry.
AB  - AIM: To identify criteria for predicting successful drainage of unresectable
      malignant hilar biliary strictures (UMHBS) because no ideal strategy currently
      exists. METHODS: We examined 78 patients with UMHBS who underwent biliary
      drainage. Drainage was considered effective when the serum bilirubin level
      decreased by >= 50% from the value before stent placement within 2 wk after
      drainage, without additional intervention. Complications that occurred within 7 d
      after stent placement were considered as early complications. Before drainage,
      the liver volume of each section (lateral and medial sections of the left liver
      and anterior and posterior sections of the right liver) was measured using
      computed tomography (CT) volumetry. Drained liver volume was calculated based on
      the volume of each liver section and the type of bile duct stricture (according
      to the Bismuth classification). Tumor volume, which was calculated by using CT
      volumetry, was excluded from the volume of each section. Receiver operating
      characteristic (ROC) analysis was performed to identify the optimal cutoff values
      for drained liver volume. In addition, factors associated with the effectiveness
      of drainage and early complications were evaluated. RESULTS: Multivariate
      analysis showed that drained liver volume [odds ratio (OR) = 2.92, 95%CI: 1.648
      5.197; P < 0.001] and impaired liver function (with decompensated liver
      cirrhosis) (OR = 0.06, 95%CI: 0.009-0.426; P = 0.005) were independent factors
      contributing to the effectiveness of drainage. ROC analysis for effective
      drainage showed cutoff values of 33% of liver volume for patients with preserved
      liver function (with normal liver or compensated liver cirrhosis) and 50% for
      patients with impaired liver function (with decompensated liver cirrhosis). The
      sensitivity and specificity of these cutoff values were 82% and 80% for preserved
      liver function, and 100% and 67% for impaired liver function, respectively. Among
      patients who met these criteria, the rate of effective drainage among those with
      preserved liver function and impaired liver function was 90% and 80%,
      respectively. The rates of effective drainage in both groups were significantly
      higher than in those who did not fulfill these criteria (P < 0.001 and P = 0.02,
      respectively). Drainage-associated cholangitis occurred in 9 patients (12%). A
      smaller drained liver volume was associated with drainage-associated cholangitis
      (P < 0.01). CONCLUSION: Liver volume drainage >= 33% in patients with preserved
      liver function and >= 50% in patients with impaired liver function correlates
      with effective biliary drainage in UMHBS.

PMID- 25945010
TI  - Prognostic value of neutrophil distribution in cholangiocarcinoma.
AB  - AIM: To explore the relationship of clinicopathological features and the
      distribution of neutrophils in the tumor microenvironment with the prognosis of
      cholangiocarcinoma. METHODS: Two hundred and fifty-four formalin-fixed and
      paraffin embedded tissue blocks were analyzed, including tissues from
      cholangiocarcinoma (n = 254), and tumor adjacent tissues (n = 238). Tissue
      sections were stained for CD15 using immunohistochemical staining. CD15
      expression was detected to identify the distribution of neutrophils in the local
      tumor microenvironment. The neutrophil density of the tumor tissues and the
      adjacent tumor tissues was detected to reflect their inflammatory status.
      Clinical data and follow-up information of cholangiocarcinoma patients who
      underwent surgery from January 2004 to December 2010 were analyzed
      retrospectively. The relationship between clinicopathological features and the
      distribution of neutrophils with prognosis of the patients were analyzed.
      RESULTS: The positive expression level of CD15 was only significantly related to
      the TNM stage. CD15 expression was higher in tumor tissues than in adjacent
      tissues (73.6% vs 54.6%), with significant differences. Patients with high
      expression of CD15 had significantly shorter overall survival (OS) than those
      with low expression of CD15 (median overall survival time 39.77 mo vs 16.87 mo, P
      = 0.008). Patients with high CD15 expression had significantly shorter disease
      free survival time (DFS) than those with low expression of CD15 (median DFS 38.27
      mo vs 16.83 mo, P = 0.029). COX multivariate analysis indicated that high CD15
      expression in tumor tissues was an independent risk factor for predicting OS for
      patients with cholangiocarcinoma [P = 0.012, relative risk (RR) = 1.601], but it
      was not an independent risk factor for predicting DFS (P = 0.073, RR = 1.462).
      CONCLUSION: Patients with high CD15 expression in cancer tissues had shorter DFS
      and OS. High expression of CD15 is an independent risk factor for OS.

PMID- 25945009
TI  - Characteristics of gastric cancer in peptic ulcer patients with Helicobacter
      pylori infection.
AB  - AIM: To evaluate the incidence and clinical characteristics of gastric cancer
      (GC) in peptic ulcer patients with Helicobacter pylori (H. pylori) infection.
      METHODS: Between January 2003 and December 2013, the medical records of patients
      diagnosed with GC were retrospectively reviewed. Those with previous gastric
      ulcer (GU) and H. pylori infection were assigned to the HpGU-GC group (n = 86)
      and those with previous duodenal ulcer (DU) disease and H. pylori infection were
      assigned to the HpDU-GC group (n = 35). The incidence rates of GC in the HpGU-GC
      and HpDU-GC groups were analyzed. Data on demographics (age, gender, peptic ulcer
      complications and cancer treatment), GC clinical characteristics [location,
      pathological diagnosis, differentiation, T stage, Lauren's classification,
      atrophy of surrounding mucosa and intestinal metaplasia (IM)], outcome of
      eradication therapy for H. pylori infection, esophagogastroduodenoscopy number
      and the duration until GC onset were reviewed. Univariate and multivariate
      analyses were performed to identify factors influencing GC development. The
      relative risk of GC was evaluated using a Cox proportional hazards model.
      RESULTS: The incidence rates of GC were 3.60% (86/2387) in the HpGU-GC group and
      1.66% (35/2098) in the HpDU-GC group. The annual incidence was 0.41% in the HpGU
      GC group and 0.11% in the HpDU-GC group. The rates of moderate-to-severe atrophy
      of the surrounding mucosa and IM were higher in the HpGU-GC group than in the
      HpDU-GC group (86% vs 34.3%, respectively, and 61.6% vs 14.3%, respectively, P <
      0.05). In the univariate analysis, atrophy of surrounding mucosa, IM and
      eradication therapy for H. pylori infection were significantly associated with
      the development of GC (P < 0.05). There was no significant difference in the
      prognosis of GC patients between the HpGU-GC and HpDU-GC groups (P = 0.347). The
      relative risk of GC development in the HpGU-GC group compared to that of the HpDU
      GC group, after correction for age and gender, was 1.71 (95%CI: 1.09-2.70; P =
      0.02). CONCLUSION: GU patients with H. pylori infection had higher GC incidence
      rates and relative risks. Atrophy of surrounding mucosa, IM and eradication
      therapy were associated with GC.

PMID- 25945011
TI  - Laparoscopic resection of lower rectal cancer with telescopic anastomosis without
      abdominal incisions.
AB  - AIM: To assess laparoscopic radical resection of lower rectal cancer with
      telescopic anastomosis through transanal resection without abdominal incisions.
      METHODS: From March 2010 to June 2014, 30 patients (14 men and 16 women, aged 36
      78 years, mean age 59.8 years) underwent laparoscopic radical resection of lower
      rectal cancer with telescopic anastomosis through anus-preserving transanal
      resection. The tumors were 5-7 cm away from the anal margin in 24 cases, and 4 cm
      in six cases. In preoperative assessment, there were 21 cases of T1N0M0 and nine
      of T2N0M0. Through the middle approach, the sigmoid mesentery was freed at the
      root with an ultrasonic scalpel and the roots of the inferior mesenteric artery
      and vein were dissected, clamped and cut. Following the total mesorectal excision
      principle, the rectum was separated until the anorectal ring reached 3-5 cm from
      the distal end of the tumor. For perineal surgery, a ring incision was made 2 cm
      above the dentate line, and sharp dissection was performed submucosally towards
      the superior direction, until the plane of the levator ani muscle, to transect
      the rectum. The rectum and distal sigmoid colon were removed together from the
      anus, followed by a telescopic anastomosis between the full thickness of the
      proximal colon and the mucosa and submucosal tissue of the rectum. RESULTS: For
      the present cohort of 30 cases, the mean operative time was 178 min, with an
      average of 13 positive lymph nodes detected. One case of postoperative
      anastomotic leak was observed, requiring temporary colostomy, which was closed
      and recovered 3 mo later. The postoperative pathology showed T1-T2N0M0 in 19
      cases and T2N1M0 in 11 cases. Twelve months after surgery, 94.4% patients
      achieved anal function Kirwan grade 1, indicating that their anal function
      returned to normal. The patients were followed up for 1-36 mo, with an average of
      23 mo. There was no local recurrence, and 17 patients survived for > 3 years
      (with a survival rate of 100%). CONCLUSION: Laparoscopic radical resection of
      lower rectal cancer with telescopic anastomosis through transanal resection
      without abdominal incisions is safe and feasible.

PMID- 25945012
TI  - Metadoxine improves the three- and six-month survival rates in patients with
      severe alcoholic hepatitis.
AB  - AIM: To evaluate the impact of metadoxine (MTD) on the 3- and 6-mo survival of
      patients with severe alcoholic hepatitis (AH). METHODS: This study was an open
      label clinical trial, performed at the "Hospital General de Mexico, Dr. Eduardo
      Liceaga". We randomized 135 patients who met the criteria for severe AH into the
      following groups: 35 patients received prednisone (PDN) 40 mg/d, 35 patients
      received PDN+MTD 500 mg three times daily, 33 patients received pentoxifylline
      (PTX) 400 mg three times daily, and 32 patients received PTX+MTD 500 mg three
      times daily. The duration of the treatment for all of the groups was 30 d.
      RESULTS: In the groups treated with the MTD, the survival rate was higher at 3 mo
      (PTX+MTD 59.4% vs PTX 33.3%, P = 0.04; PDN+MTD 68.6% vs PDN 20%, P = 0.0001) and
      at 6 mo (PTX+MTD 50% vs PTX 18.2%, P = 0.01; PDN+MTD 48.6% vs PDN 20%, P = 0.003)
      than in the groups not treated with MTD. A relapse in alcohol intake was the
      primary independent factor predicting mortality at 6 mo. The patients receiving
      MTD maintained greater abstinence than those who did not receive it (74.5% vs
      59.4%, P = 0.02). CONCLUSION: MTD improves the 3- and 6-mo survival rates in
      patients with severe AH. Alcohol abstinence is a key factor for survival in these
      patients. The patients who received the combination therapy with MTD were more
      likely to maintain abstinence than those who received monotherapy with either PDN
      or PTX.

PMID- 25945014
TI  - Role of colonoscopy in the diagnostic work-up of bowel endometriosis.
AB  - AIM: To evaluate the accuracy of colonoscopy for the prediction of intestinal
      involvement in deep pelvic endometriosis. METHODS: This prospective observational
      study was performed between September 2011 and July 2014. Only women with both a
      clinical and imaging diagnosis of deep pelvic endometriosis were included. The
      study was approved by the local ethics committee and written informed consent was
      obtained in all cases. Both colonoscopy and laparoscopy were performed by expert
      surgeons with a high level of expertise with these techniques. Laparoscopy was
      performed within 4 wk of colonoscopic examination. All hypothetical colonoscopy
      findings (eccentric wall thickening with or without surface nodularities and
      polypoid lesions with or without surface nodularities of endometriosis) were
      compared with laparoscopic and histological findings. We calculated the
      sensitivity, specificity, positive predictive value and negative predictive value
      for the presence of colonoscopic findings of intestinal endometriosis. RESULTS: A
      total of 174 consecutive women aged between 21-42 years with a diagnosis of deep
      pelvic endometriosis who underwent colonoscopy and surgical intervention were
      included in our analysis. In 76 of the women (43.6%), intestinal endometrial
      implants were found at surgery and histopathological examination. Specifically,
      38 of the 76 lesions (50%) were characterized by the presence of serosal bowel
      nodules; 28 of the 76 lesions (36.8%) reached the muscularis layer; 8 of the 76
      lesions (10.5%) reached the submucosa; and 2 of the 76 lesions (2.6%) reached the
      mucosa. Colonoscopic findings suggestive of intestinal endometriosis were
      detected in 7 of the 174 (4%) examinations. Colonoscopy failed to diagnose
      intestinal endometriosis in 70 of the 76 women (92.1%). A colonoscopic diagnosis
      of endometriosis was obtained in all cases of mucosal involvement, in 3 of 8
      cases (37.5%) of submucosal involvement, in no cases of muscularis layer
      involvement and in 1 of 38 cases (2.6%) of serosa involvement. The sensitivity,
      specificity, positive predictive and negative predictive values of colonoscopy
      for the diagnosis of intestinal endometriosis were 7%, 98%, 85% and 58%,
      respectively. CONCLUSION: Being an invasive procedure, colonoscopy should not be
      routinely performed in the diagnostic work-up of bowel endometriosis.

PMID- 25945013
TI  - Moxibustion combined with acupuncture increases tight junction protein expression
      in Crohn's disease patients.
AB  - AIM: To investigate the effect of herb-partitioned moxibustion combined with
      acupuncture on the expression of intestinal epithelial tight junction (TJ)
      proteins. METHODS: Sixty patients diagnosed with mild to moderate Crohn's disease
      (CD) were allocated into the herb-partitioned moxibustion combined with
      acupuncture (HMA) group (n = 30) or the mesalazine (MESA) group (n = 30) using a
      parallel control method. There were 2 sets of acupoints used alternately for HMA
      treatment. The following points were included in Set A: ST25 (Tianshu), RN6
      (Qihai), and RN9 (Shuifen) for herb-partitioned moxibustion and ST36 (Zusanli),
      ST37 (Shangjuxu), LI11 (Quchi), and LI4 (Hegu) for acupuncture. The points for
      Set B included BL23 (Shenshu) and BL25 (Dachangshu) for herb-partitioned
      moxibustion and EX-B2 of T6-T1 (Jiajixue) for acupuncture. The patients received
      the same treatment 6 times a week for 12 consecutive weeks. The MESA group
      received 1 g of mesalazine enteric coated tablets 4 times daily for 12
      consecutive weeks. Intestinal tissues were stained and examined to compare the
      morphological and ultrastructural changes before and after the treatment session.
      Immunohistochemistry and in situ hybridization assays were used to detect the
      expression of intestinal epithelial TJ proteins zonula occludens-1 (ZO-1),
      occludin, and claudin-1. The mRNA levels were also evaluated. RESULTS: After the
      treatment, both herb-partitioned moxibustion combined with acupuncture and
      mesalazine improved intestinal morphology and ultrastructure of CD patients; the
      patients treated with HMA showed better improvement. HMA significantly increased
      the expression of ZO-1 (P = 0.000), occludin (P = 0.021), and claudin-1 (P =
      0.016). MESA significantly increased the expression of ZO-1 (P = 0.016) and
      occludin (P = 0.026). However, there was no significant increase in the
      expression of claudin-1 (P = 0.935). There was no statistically significant
      difference between the two groups for the expression of occludin and claudin-1 (P
      > 0.05). The HMA group showed a significant improvement in ZO-1 expression
      compared to the MESA group (2333.34 +/- 352.51 vs 2160.38 +/- 307.08, P = 0.047).
      HMA significantly increased the expression of ZO-1 mRNA (P = 0.000), occludin
      mRNA (P = 0.017), and claudin-1 mRNA (P = 0.017). MESA significantly increased
      the expression of ZO-1 mRNA (P = 0.000), occludin mRNA (P = 0.042), and claudin-1
      mRNA (P = 0.041). There was no statistically significant difference between the
      two groups in the expression of occludin and claudin-1 mRNA (P > 0.05). However,
      the HMA group showed a significant improvement in ZO-1 mRNA expression compared
      with the MESA group (2378.17 +/- 308.77 vs 2200.56 +/- 281.88, P = 0.023).
      CONCLUSION: HMA can repair intestinal epithelial barrier lesions and relieve
      inflammation by upregulating the expression of TJ proteins and their mRNAs.

PMID- 25945015
TI  - In vivo gastric mucosal histopathology using endocytoscopy.
AB  - AIM: To study the ability of endocytoscopy to identify normal gastric mucosa and
      to exclude Helicobacter pylori (H. pylori) infection. METHODS: Endocytoscopic
      examination of the gastric corpus and antrum was performed in 70 consecutive
      patients. Target biopsy specimens were also obtained from the assessed region and
      multiple H. pylori tests were performed. The normal endocytoscopy patterns of the
      corpus and antrum were divided into the normal pit-dominant type (n-Pit) or the
      normal papilla-dominant type (n-Pap), respectively characterized as either
      regular pits with capillary networks or round, smooth papillary structures with
      spiral capillaries. On the other hand, normal mucosa was defined as mucosa not
      demonstrating histological abnormalities, including inflammation and atrophy.
      RESULTS: The sensitivity and specificity of n-Pit for normal mucosa in the
      gastric corpus were 94.4% and 97.1%, respectively, whereas those of n-Pap for
      normal mucosa in the antrum were 92.0% and 86.7%, respectively. The positive
      predictive values of n-Pit and n-Pap for H. pylori-negative tissue were 88.6% and
      93.1%, respectively, and their negative predictive values for H. pylori-negative
      tissues were 42.9% and 41.5%, respectively. The inter-observer agreement for
      determining n-Pit and n-Pap for normal mucosa were 0.857 and 0.769, respectively,
      which is considered reliable. CONCLUSION: N-Pit and n-Pap, seen using EC, are
      considered useful predictors of normal mucosa and the absence of H. pylori
      infection.

PMID- 25945016
TI  - Pathophysiology of functional heartburn based on Rome III criteria in Japanese
      patients.
AB  - AIM: To investigate the pathophysiology of functional heartburn (FH) in Japanese
      patients. METHODS: A total of 111 patients with proton pump inhibitor (PPI)
      refractory non-erosive gastroesophageal reflux disease underwent intraesophageal
      pressure testing and 24-h multichannel intraluminal impedance-pH (24MII-pH)
      testing. The patients also completed several questionnaires while they were
      receiving the PPI treatment, including the questionnaire for the diagnosis of
      reflux disease (QUEST), the frequency scale for the symptoms of gastroesophageal
      reflux disease (FSSG), the gastrointestinal symptoms rating scale (GSRS), SF-36,
      and the Cornell Medical Index (CMI). The subjects were classified into FH and
      endoscopy-negative reflux disease (ENRD) groups based on the Rome III criteria.
      RESULTS: Thirty-three patients with esophageal motility disorder were excluded
      from this study, while 22 patients with abnormal esophageal acid exposure time
      (pH-POS) and 34 with hypersensitive esophagus (HE) were included in the ENRD
      group. The FH group included 22 patients with no reflux involvement. Sex, age,
      and body mass index did not differ significantly between the groups. The mean SF
      36 values were < 50 (normal) for all scales in these groups, with no significant
      differences. The GSRS scores in these groups were not different and showed
      overlap with other gastrointestinal symptoms. The QUEST and the FSSG scores did
      not differ significantly between the groups. Neuroticism was diagnosed using the
      CMI questionnaire in 17 of the 78 included subjects within the pH-POS (n = 4), HE
      (n = 8), and FH (n = 5) groups, with no significant differences. CONCLUSION:
      Clinical characteristics of the FH and PPI-refractory ENRD groups were similar.
      Therefore, esophageal function should be examined via manometry and 24MII-pH
      testing to differentiate between them.

PMID- 25945017
TI  - Usefulness of two-point Dixon fat-water separation technique in gadoxetic acid
      enhanced liver magnetic resonance imaging.
AB  - AIM: To compare differences between volumetric interpolated breath-hold
      examination (VIBE) using two-point Dixon fat-water separation (Dixon-VIBE) and
      chemically selective fat saturation (FS-VIBE) with magnetic resonance imaging
      examination. METHODS: Forty-nine patients were included, who were scanned with
      two VIBE sequences (Dixon-VIBE and FS-VIBE) in hepatobiliary phase after
      gadoxetic acid administration. Subjective evaluations including sharpness of
      tumor, sharpness of vessels, strength and homogeneity of fat suppression, and
      artifacts that were scored using a 4-point scale. The liver-to-lesion contrast
      was also calculated and compared. RESULTS: Dixon-VIBE with water reconstruction
      had significantly higher subjective scores than FS-VIBE in strength and
      homogeneity of fat suppression (< 0.0001) but lower scores in sharpness of tumor
      (P < 0.0001), sharpness of vessels (P = 0.0001), and artifacts (P = 0.034). The
      liver-to-lesion contrast on Dixon-VIBE images was significantly lower than that
      on FS-VIBE (16.6% +/- 9.4% vs 23.9% +/- 12.1%, P = 0.0001). CONCLUSION: Dixon
      VIBE provides stronger and more homogenous fat suppression than FS-VIBE, while
      has lower clarity of focal liver lesions in hepatobiliary phase after gadoxetic
      acid administration.

PMID- 25945018
TI  - Irsogladine maleate and rabeprazole in non-erosive reflux disease: A double
      blind, placebo-controlled study.
AB  - AIM: To evaluate the efficacy of adding irsogladine maleate (IM) to proton-pump
      inhibitor (PPI) therapy in non-erosive reflux disease (NERD) treatment. METHODS:
      One hundred patients with NERD were recruited and randomized to receive
      rabeprazole plus IM (group I) or rabeprazole plus placebo (group P). The efficacy
      of the treatment was assessed using the Frequency Scale for the Symptoms of
      Gastroesophageal Reflux Disease (FSSG) and the short form (SF)-36 quality of life
      questionnaires after four weeks of treatment. We also assessed whether patients
      with NERD with minimal changes (grade M) had different responses to the therapies
      compared with patients who did not have minimal changes (grade N). RESULTS: Group
      I and group P showed significant improvements in their FSSG scores after the
      treatment (from 17.9 +/- 7.9 to 9.0 +/- 7.6, and from 17.7 +/- 7.3 to 11.2 +/-
      7.9, respectively, P = 0.0001), but there was no statistically significant
      difference between the FSSG scores in group I and those in group P. Subgroup
      analysis showed that significant improvements in the FSSG scores occurred in the
      patients in group I who had NERD grade N (modified Los Angeles classification)
      (7.8 +/- 7.4 vs 12.5 +/- 9.8, P = 0.041). The SF-36 scores for patients with NERD
      grade N who had received IM and rabeprazole were significantly improved in
      relation to their vitality and mental health scores. CONCLUSION: The addition of
      IM to rabeprazole significantly improves gastroesophageal reflux disease symptoms
      and the quality of the lives of patients with NERD grade N.

PMID- 25945019
TI  - Efficacy of moxifloxacin-based sequential therapy for first-line eradication of
      Helicobacter pylori infection in gastrointestinal disease.
AB  - AIM: To evaluate the efficacy of 14-d moxifloxacin-based sequential therapy as
      first-line eradication treatment of Helicobacter pylori (H. pylori) infection.
      METHODS: From December 2013 to August 2014, 161 patients with confirmed H. pylori
      infection randomly received 14 d of moxifloxacin-based sequential group (MOX-ST
      group, n = 80) or clarithromycin-based sequential group (CLA-ST group, n = 81)
      therapy. H. pylori infection was defined on the basis of at least one of the
      following three tests: a positive (13)C-urea breath test; histologic evidence of
      H. pylori by modified Giemsa staining; or a positive rapid urease test (CLOtest;
      Delta West, Bentley, Australia) by gastric mucosal biopsy. Successful eradication
      therapy for H. pylori infection was defined as a negative (13)C-urea breath test
      four weeks after the end of eradication treatment. Compliance was defined as good
      when drug intake was at least 85%. H. pylori eradication rates, patient
      compliance with drug treatment, adverse event rates, and factors influencing the
      efficacy of eradication therapy were evaluated. RESULTS: The eradication rates by
      intention-to-treat analysis were 91.3% (73/80; 95%CI: 86.2%-95.4%) in the MOX-ST
      group and 71.6% (58/81; 95%CI: 65.8%-77.4%) in the CLA-ST group (P = 0.014). The
      eradication rates by per-protocol analysis were 93.6% (73/78; 95%CI: 89.1%-98.1%)
      in the MOX-ST group and 75.3% (58/77; 95%CI: 69.4%-81.8%) in the CLA-ST group (P
      = 0.022). Compliance was 100% in both groups. The adverse event rates were 12.8%
      (10/78) and 24.6% (19/77) in the MOX-ST and CLA-ST group, respectively (P =
      0.038). Most of the adverse events were mild-to-moderate in intensity; there was
      none serious enough to cause discontinuation of treatment in either group. In
      multivariate analysis, advanced age (>= 60 years) was a significant independent
      factor related to the eradication failure in the CLA-ST group (adjusted OR =
      2.13, 95%CI: 1.97-2.29, P = 0.004), whereas there was no significance in the MOX
      ST group. CONCLUSION: The 14-d moxifloxacin-based sequential therapy is
      effective. Moreover, it shows excellent patient compliance and safety compared to
      the 14-d clarithromycin-based sequential therapy.

PMID- 25945020
TI  - Hepatitis B virus preS1 deletion is related to viral replication increase and
      disease progression.
AB  - AIM: To investigate the clinical implications of hepatitis B virus (HBV) preS1
      deletion. METHODS: We developed a fluorescence resonance energy transfer-based
      real-time polymerase chain reaction (RT-PCR) that can detect four genotypes (wild
      type, 15-bp, 18-bp and 21-bp deletion). The PCR method was used in two cohorts of
      Korean chronic HBV subjects with genotype C infections. Cohort I included 292
      chronic HBV subjects randomly selected from Cheju National University Hospital
      (Jeju, South Korea) or Seoul National University Hospital (Seoul, South Korea),
      and cohort II included 90 consecutive chronic HBV carriers recruited from Konkuk
      University Hospital (Seoul, South Korea); the cohort II patients did not have
      hepatocellular carcinoma or liver cirrhosis. RESULTS: The method proposed in this
      study identified 341 of 382 samples (89.3%). Deletion variants were identified in
      100 (29.3%) of the 341 detected samples. In both cohorts, the subjects with
      deletions had a significantly higher Hepatitis B virus e antigen (HBeAg)-positive
      seroprevalence [cohort I, wild (51.0%) vs deletion (75.0%), P < 0.001; cohort II,
      wild (69.2%) vs deletion (92.9%), P = 0.002] and higher HBV DNA levels [cohort I,
      wild (797.7 pg/mL) vs deletion (1678.9 pg/mL), P = 0.013; cohort II, wild (8.3 *
      10(8) copies/mL) vs deletion (2.2 * 10(9) copies/mL), P = 0.049], compared to
      subjects with wild type HBV. CONCLUSION: HBV genotype C preS1 deletion may affect
      disease progression in chronic HBV subjects through an extended duration of HBeAg
      seropositive status and increased HBV replications.

PMID- 25945021
TI  - Anterior rectopexy for full-thickness rectal prolapse: Technical and functional
      results.
AB  - AIM: To assess effectiveness, complications, recurrence rate, and recent
      improvements of the anterior rectopexy procedure for treatment of total rectal
      prolapse. METHODS: MEDLINE, PubMed, EMBASE, and other relevant database were
      searched to identify studies. Randomized controlled trials, non-randomized
      studies and original articles in English language, with more than 10 patients who
      underwent laparoscopic ventral rectopexy for full-thickness rectal prolapse, with
      a follow-up over 3 mo were considered for the review. RESULTS: Twelve non
      randomized case series studies with 574 patients were included in the review. No
      surgical mortality was described. Conversion was needed in 17 cases (2.9%), most
      often due to difficult adhesiolysis. Twenty eight patients (4.8%) presented with
      major complications. Seven (1.2%) mesh-related complications were reported. Most
      frequent complications were urinary tract infection and urinary retention. Mean
      recurrence rate was 4.7% with a median follow-up of 23 mo. Improvement of
      constipation ranged from 3%-72% of the patients and worsening or new onset
      occurred in 0%-20%. Incontinence improved in 31%-84% patients who presented fecal
      incontinence at various stages. Evaluation of functional score was disparate
      between studies. CONCLUSION: Based on the low long-term recurrence rate and
      favorable outcome data in terms of low de novo constipation rate, improvement of
      anal incontinence, and low complications rate, laparoscopic anterior rectopexy
      seems to emerge as an efficient procedure for the treatment of patients with
      total rectal prolapse.

PMID- 25945022
TI  - Non-physician endoscopists: A systematic review.
AB  - AIM: To examine the available evidence on safety, competency and cost
      effectiveness of nursing staff providing gastrointestinal (GI) endoscopy
      services. METHODS: The literature was searched for publications reporting nurse
      endoscopy using several databases and specific search terms. Studies were
      screened against eligibility criteria and for relevance. Initial searches yielded
      74 eligible and relevant articles; 26 of these studies were primary research
      articles using original datasets relating to the ability of non-physician
      endoscopists. These publications included a total of 28883 procedures performed
      by non-physician endoscopists. RESULTS: The number of publications in the field
      of non-specialist gastrointestinal endoscopy reached a peak between 1999 and 2001
      and has decreased thereafter. 17/26 studies related to flexible sigmoidoscopies,
      5 to upper GI endoscopy and 6 to colonoscopy. All studies were from metropolitan
      centres with nurses working under strict supervision and guidance by specialist
      gastroenterologists. Geographic distribution of publications showed the majority
      of research was conducted in the United States (43%), the United Kingdom (39%)
      and the Netherlands (7%). Most studies conclude that after appropriate training
      nurse endoscopists safely perform procedures. However, in relation to endoscopic
      competency, safety or patient satisfaction, all studies had major methodological
      limitations. Patients were often not randomized (21/26 studies) and not
      appropriately controlled. In relation to cost-efficiency, nurse endoscopists were
      less cost-effective per procedure at year 1 when compared to services provided by
      physicians, due largely to the increased need for subsequent endoscopies,
      specialist follow-up and primary care consultations. CONCLUSION: Contrary to
      general beliefs, endoscopic services provided by nurse endoscopists are not more
      cost effective compared to standard service models and evidence suggests the
      opposite. Overall significant shortcomings and biases limit the validity and
      generalizability of studies that have explored safety and quality of services
      delivered by non-medical endoscopists.

PMID- 25945023
TI  - Value of bevacizumab in treatment of colorectal cancer: A meta-analysis.
AB  - AIM: To assess the efficacy and safety of bevacizumab in the treatment of
      colorectal cancer. METHODS: All randomized controlled trials of bevacizumab for
      the treatment of colorectal cancer from January 2003 to June 2013 were collected
      by searching the Cochrane Library, PubMed, Chinese National Knowledge
      Infrastructure and Wanfang databases. The primary endpoint was overall survival
      (OS), and the secondary endpoints were progression-free survival, overall
      response rate and adverse events. Two reviewers extracted data independently.
      Statistical analyses were performed with Stata 12.0. The degree of bias was
      assessed using funnel plots for the effect size of OS at the primary endpoint.
      RESULTS: Following the inclusion criteria and exclusion criteria, ten studies
      comprising 6977 cases were finally included, of which nine were considered to be
      of high quality (4-7 points) and one of low quality (1-3 points). Our meta
      analysis revealed the efficacy of bevacizumab in patients with colorectal cancer
      in terms of OS (HR = 0.848, 95%CI: 0.747-0.963), progression-free survival (HR =
      0.617, 95%CI: 0.530-0.719), and overall response rate (OR = 1.627, 95%CI: 1.199
      2.207). Regarding safety, higher rates of grade >= 3 hypertension, proteinuria,
      bleeding, thrombosis, and gastrointestinal perforation were observed in the
      bevacizumab treatment group (P < 0.05); however, the incidence of serious
      toxicity was very low. There was no publication bias in the 10 reports included
      in this meta-analysis. CONCLUSION: The clinical application of bevacizumab in
      colorectal cancer is effective with good safety.

PMID- 25945024
TI  - Relationship between apurinic endonuclease 1 Asp148Glu polymorphism and
      gastrointestinal cancer risk: An updated meta-analysis.
AB  - AIM: To evaluate the relationship between apurinic endonuclease 1 (APE1)
      Asp148Glu polymorphism and the susceptibility to gastrointestinal (GI) cancers.
      METHODS: We searched PubMed, ISI Web of Knowledge, and Chinese National Knowledge
      Infrastructure (CNKI) databases updated on July 15, 2014 for relevant studies.
      Only case-control studies comparing APE1 Asp148Glu polymorphism and GI cancer
      risk were included. We excluded studies reporting only standardized incidence
      ratios without control groups and those without detailed genotyping data. Meta
      analysis was performed on 17 studies involving 4856 cancer patients and 6136
      cancer-free controls. Review Manager version 5.1 was used to perform the meta
      analysis. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were
      estimated under the allele contrast, homozygous, heterozygous, dominant and
      recessive genetic models. We also conducted subgroup analyses stratified by
      ethnicity and cancer type. Publication bias was evaluated using Begg's test.
      RESULTS: The meta-analysis showed a significant association between APE1
      Asp148Glu polymorphism and GI cancer risk in three genetic models in the overall
      population (G vs T: OR = 1.18; 95%CI: 1.05-1.32; TG vs TT: OR = 1.28; 95%CI: 1.08
      1.52; TG + GG vs TT: OR = 1.32; 95%CI: 1.10-1.57). Stratified analysis by
      ethnicity revealed a statistically increased GI cancer risk in Asians (G vs T: OR
      = 1.27; 95%CI: 1.07-1.51; GG vs TT: OR = 1.58; 95%CI: 1.05-2.38; TG vs TT: OR =
      1.30; 95%CI, 1.01- 1.67; and TG + GG vs TT: OR = 1.38; 95%CI: 1.07-1.78), but not
      in Caucasians. Further subgroup analysis by cancer type indicated that APE1
      Asp148Glu polymorphism may contribute to gastric cancer risk. However, Asp148Glu
      has no significant association with colorectal or esophageal cancer risk in any
      genetic model. CONCLUSION: This meta-analysis suggests that the APE1 Asp148Glu
      polymorphism G allele is associated with an increased GI cancer risk, especially
      in gastric cancer.

PMID- 25945026
TI  - Endoscopic removal of a tablespoon lodged within the duodenum.
AB  - Here we report the case of a 34-year-old man who underwent endoscopic removal of
      a tablespoon from the stomach that was lodged within the duodenum. Removal
      required the use of a two-channel upper endoscope and polypectomy snares. Using
      the double-snare technique, the spoon was grasped at the proximal and distal
      parts of the handle. The double-snare was first pulled unsuccessfully and then
      pulled with simultaneous manual abdominal compression of the bulbus from the body
      surface. Compression was gently applied towards the stomach. As a result, the
      head of the spoon prolapsed from the bulbus, and was easily retracted from the
      stomach without any complications. In cases of foreign body lodging within the
      duodenum, the manual abdominal compression technique may help clinicians pull out
      the object and avoid surgery. The usefulness of manual compression is dependent
      on the foreign body's sharpness and the location. 

PMID- 25945025
TI  - Case of arterial hemorrhage after endoscopic papillary large balloon dilation for
      choledocholithiases using a covered self-expandable metallic stent.
AB  - A 78-year-old male was admitted to our hospital because of choledocholithiasis.
      ERC demonstrated choledocholithiases with a maximum diameter of 13 mm, and we
      performed endoscopic papillary large balloon dilation (EPLBD) with a size of 15
      mm. Immediately following the balloon deflation, spurting hemorrhage occurred
      from the orifice of the duodenal papilla. Although we performed endoscopic
      hemostasis by compressing the bleeding point with the large balloon catheter, we
      could not achieve hemostasis. Therefore, we placed a 10 mm fully covered self
      expandable metallic stent (SEMS) across the duodenal papilla, and the hemorrhage
      stopped immediately. After 1 wk of SEMS placement, duodenal endoscopy revealed
      ulcerative lesions in both the orifice of the duodenal papilla and the lower bile
      duct. A direct peroral cholangioscopy using an ultra-slim upper endoscope
      revealed a visible vessel with a longitudinal mucosal tear in the ulceration of
      the lower bile duct. We believe that the mucosal tear and subsequent ruptured
      vessel were caused by the EPLBD procedure. 

PMID- 25945027
TI  - Oxyntic gland adenoma endoscopically mimicking a gastric neuroendocrine tumor: A
      case report.
AB  - Gastric adenocarcinoma is one of the most common malignancies worldwide.
      Histochemical and immunohistologic analyses classify the phenotypes of gastric
      adenocarcinoma into several groups based on the variable clinical and pathologic
      features. A new and rare variant of gastric adenocarcinoma with chief cell
      differentiation (GA-CCD) has recently been recognized. Studies reporting the
      distinct clinicopathologic characteristics proposed the term oxyntic gland
      polyp/adenoma because of the benign nature of the GA-CCD. Typically, GA-CCD is a
      solitary mucosal lesion that develops either in the gastric cardia or fundus.
      Histologically, this lesion is characterized by tightly clustered glands and
      anastomosing cords of chief cells. Immunohistochemically, GA-CCD is diffusely
      positive for mucin (MUC) 6 and negative for MUC2 and MUC5AC. However, other
      gastric tumors such as a gastric neuroendocrine tumor or fundic gland polyp have
      been difficult to exclude. Because GA-CCD tends to be endoscopically misdiagnosed
      as a neuroendocrine tumor or fundic gland polyp, comprehensive assessment and
      observation by an endoscopist are strongly recommended. Herein, we report a rare
      case of oxyntic gland adenoma endoscopically mimicking a gastric neuroendocrine
      tumor that was successfully removed by endoscopic mucosal resection. 

PMID- 25945028
TI  - Nonconvulsive status epilepticus disguising as hepatic encephalopathy.
AB  - Nonconvulsive status epilepticus has become an important issue in modern
      neurology and epileptology. This is based on difficulty in definitively
      elucidating the condition and its various clinical phenomena and on our
      inadequate insight into the intrinsic pathophysiological processes. Despite
      nonconvulsive status epilepticus being a situation that requires immediate
      treatment, this disorder may not be appreciated as the cause of mental status
      impairment. Although the pathophysiology of nonconvulsive status epilepticus
      remains unknown, this disorder is thought to lead to neuronal damage, so its
      identification and treatment are important. Nonconvulsive status epilepticus
      should be considered in the differential diagnosis of patients with liver
      cirrhosis presenting an altered mental status. We report a case of a 52-year-old
      male with liver cirrhosis presenting an altered mental status. He was initially
      diagnosed with hepatic encephalopathy but ultimately diagnosed with nonconvulsive
      status epilepticus by electroencephalogram. 

PMID- 25945029
TI  - Management of post-gastrectomy anastomosis site obstruction with a self
      expandable metallic stent.
AB  - Post-gastrectomy anastomosis site obstruction is a relatively rare complication
      after a subtotal gastrectomy. We present a case of a 75-year-old man who
      underwent a truncal vagotomy, omental patch, gastrojejunostomy, and Braun
      anastomosis for duodenal ulcer perforation and a gastric outlet obstruction.
      Following the 10(th) postoperative day, the patient complained of abdominal
      discomfort and vomiting. We diagnosed post-gastrectomy anastomosis site
      obstruction by an upper gastrointestinal series and an upper endoscopic
      examination. We inserted a self-expandable metallic stent (SEMS) at the
      anastomosis site. The stent was fully expanded after deployment. On the day
      following the stent insertion, the patient began to eat, and his abdominal
      discomfort was resolved. This paper describes the successful management of post
      gastrectomy anastomosis site obstruction with temporary placement of a SEMS. 

PMID- 25945030
TI  - Surgical effects of nasal transposition of inferior rectus muscle - 135 cases of
      acquired superior oblique palsy.
AB  - Nasal transposition of the inferior rectus (IR) muscle, which is transposed
      nasally with the insertion parallel to the spiral of Tillaux, could correct
      excyclotropia. However, as far as we are aware, there have been no reports
      examining the surgical effects of this procedure in multiple cases. Therefore, we
      examined the surgical effects of IR nasal transposition in 135 cases with
      acquired trochlear nerve palsy at Hyogo College of Medicine Hospital,
      Nishinomiya, Japan. One muscle width of IR nasal transposition corrected an
      average 5.6 degrees  in excyclotorsion, while bilateral IR nasal transposition
      corrected average 10.9 degrees . This result shows this procedure is accurate
      quantitatively. Moreover, IR nasal transposition in combination with IR recession
      or resection can correct vertical deviation and excyclotorsion simultaneously.
      The results of this study suggest that IR nasal transposition should become first
      line treatment for acquired superior oblique palsy. 

PMID- 25945032
TI  - Infected ptosis surgery - a rare complication from a multidrug-resistant
      organism.
AB  - A 7-year-old boy had a case of congenital ptosis of the right eye and has
      undergone frontalis sling surgery using Gore-tex material. There was no
      intraoperative or immediate postoperative complication. However, the patient
      defaulted his follow-up and presented with right eye preseptal abscess secondary
      to infected surgical wound 1 month after surgery. He was treated with multiple
      antibiotics and underwent repeated incision and drainage procedures. However,
      there was still no resolution of the right eye preseptal abscess. The patient's
      condition subsequently improved after removal of the Gore-tex material and
      treatment with an antibiotic combination of ceftazidime and amikacin.
      Microbiological analysis finally isolated the multidrug resistant Acinetobacter
      species. At 6 months follow-up, his right upper eyelid was healed with scarring,
      but without ptosis. 

PMID- 25945031
TI  - Keratoprostheses for corneal blindness: a review of contemporary devices.
AB  - According to the World Health Organization, globally 4.9 million are blind due to
      corneal pathology. Corneal transplantation is successful and curative of the
      blindness for a majority of these cases. However, it is less successful in a
      number of diseases that produce corneal neovascularization, dry ocular surface
      and recurrent inflammation, or infections. A keratoprosthesis or KPro is the only
      alternative to restore vision when corneal graft is a doomed failure. Although a
      number of KPros have been proposed, only two devices, Boston type-1 KPro and
      osteo-odonto-KPro, have came to the fore. The former is totally synthetic and the
      latter is semi-biological in constitution. These two KPros have different
      surgical techniques and indications. Keratoprosthetic surgery is complex and
      should only be undertaken in specialized centers, where expertise,
      multidisciplinary teams, and resources are available. In this article, we briefly
      discuss some of the prominent historical KPros and contemporary devices. 

PMID- 25945033
TI  - A 3-day regimen with azithromycin 1.5% eyedrops for the treatment of purulent
      bacterial conjunctivitis in children: efficacy on clinical signs and impact on
      the burden of illness.
AB  - PURPOSE: To compare the efficacy of azithromycin 1.5% versus tobramycin 0.3%
      eyedrops on clinical ocular signs and symptoms of bacterial conjunctivitis in
      children and to assess the parents' satisfaction regarding the dosing regimen.
      PATIENTS AND METHODS: An international, multicenter, randomized, investigator
      masked, controlled clinical trial conducted in children (1 day to 18 years old)
      with bulbar conjunctival hyperemia and purulent discharge. Azithromycin 1.5% was
      administered as 1 drop twice daily for 3 days, and tobramycin 0.3% as 1 drop
      every 2 hours for 2 days, then 4 times daily for 5 days. RESULTS: A total of 286
      patients (mean age: 3.2 years) were enrolled. In children with bacteriologically
      positive cultures (N=203), azithromycin produced a significantly greater
      improvement in conjunctival discharge (P<0.01) and a trend (P=0.054) toward
      improvement in conjunctival hyperemia at day 7 than did tobramycin. Complete
      resolution of conjunctival discharge was significantly more frequent at day 3 on
      azithromycin than tobramycin (P=0.005). More parents found azithromycin easier to
      use (in terms of treatment duration, total number of instillations, instilling
      drops during the day, and difficulty in performing daily activities) than
      tobramycin. CONCLUSION: The azithromycin 1.5% regimen produced a rapid resolution
      of cardinal signs of purulent bacterial conjunctivitis with a more convenient
      dosage regimen. Such improved convenience is likely to improve compliance and
      lessen the burden of illness for patients and carers.

PMID- 25945034
TI  - Canakinumab as rescue therapy in familial Mediterranean fever refractory to
      conventional treatment.
AB  - Familial Mediterranean fever is an autosomal recessive autoinflammatory disorder
      mainly affecting Mediterranean populations, which is associated with mutations of
      the MEFV gene that encodes pyrin. Functional studies suggest that pyrin is
      implicated in the maturation and secretion of interleukin-1 (IL-1). The IL-1
      receptor antagonist or anti-IL-1 monoclonal antibody may therefore represent a
      rational approach for the treatment of the rare patients who are refractory to
      conventional therapy. We report the case of a young female affected by familial
      Mediterranean fever who proved to be resistant to colchicine and was successfully
      treated with canakinumab. 

PMID- 25945035
TI  - Promoting endothelial function by S-nitrosoglutathione through the HIF
      1alpha/VEGF pathway stimulates neurorepair and functional recovery following
      experimental stroke in rats.
AB  - BACKGROUND: For stroke patients, stimulating neurorepair mechanisms is necessary
      to reduce morbidity and disability. Our previous studies on brain and spinal cord
      trauma show that exogenous treatment with the S-nitrosylating agent S
      nitrosoglutathione (GSNO) - a nitric oxide and glutathione metabolite of the
      human body - stimulates neurorepair and aids functional recovery. Using a rat
      model of cerebral ischemia and reperfusion (IR) in this study, we tested the
      hypothesis that GSNO invokes the neurorepair process and improves neurobehavioral
      functions through the angiogenic HIF-1alpha/VEGF pathway. METHODS: Stroke was
      induced by middle cerebral artery occlusion for 60 minutes followed by
      reperfusion in adult male rats. The injured animals were treated with saline (IR
      group, n=7), GSNO (0.25 mg/kg, GSNO group, n=7), and GSNO plus the HIF-1alpha
      inhibitor 2-methoxyestra-diol (2-ME) (0.25 mg/kg GSNO + 5.0 mg/kg 2-ME, GSNO + 2
      ME group, n=7). The groups were studied for either 7 or 14 days to determine
      neurorepair mediators and functional recovery. Brain capillary endothelial cells
      were used to show that GSNO promotes angiogenesis and that GSNO-mediated
      induction of VEGF and the stimulation of angiogenesis are dependent on HIF-1alpha
      activity. RESULTS: IR injury increased the expression of neurorepair mediators
      HIF-1alpha, VEGF, and PECAM-1 and vessel markers to a limited degree that
      correlate well with significantly compromised neurobehavioral functions compared
      with sham animals. GSNO treatment of IR not only remarkably enhanced further the
      expression of HIF-1alpha, VEGF, and PECAM-1 but also improved functioning
      compared with IR. The GSNO group also had a higher degree of vessel density than
      the IR group. Increased expression of VEGF and the degree of tube formation
      (angiogenesis) by GSNO were reduced after the inhibition of HIF-1alpha by 2-ME in
      an endothelial cell culture model. 2-ME treatment of the GSNO group also blocked
      not only GSNO's effect of reduced infarct volume, decreased neuronal loss, and
      enhanced expression of PECAM-1 (P<0.001), but also its improvement of motor and
      neurological functions (P<0.001). CONCLUSION: GSNO stimulates the process of
      neurorepair, promotes angiogenesis, and aids functional recovery through the HIF
      1alpha-dependent pathway, showing therapeutic and translational promise for
      stroke.

PMID- 25945036
TI  - Comparison of reendothelialization and neointimal formation with stents coated
      with antibodies against endoglin and CD34 in a porcine model.
AB  - Anti-CD34 coated stents are the only commercialized antibody-coated stents
      currently used for coronary artery diseases with various limitations. Endoglin
      plays important roles in the proliferation of endothelial cells and vascular
      remodeling and could be an ideal target surface molecule. The objective of this
      study was to investigate the efficacy of stents coated with anti-endoglin
      antibodies (ENDs) in terms of endothelial recovery and the reduction of
      neointimal formation. The performance of ENDs was evaluated by comparing with
      stents coated with anti-CD34 antibodies (CD34s), sirolimus-eluting stents (SESs),
      and bare metal stents (BMSs). Stents were randomly assigned and placed in the
      coronary arteries of juvenile pigs. Histomorphometric analysis and scanning
      electron microscopy were performed after stent implantation. Our results showed
      at 14 days after stent implantation, the neointima area and percent area stenosis
      in ENDs and CD34s were remarkably decreased compared with those in BMSs and SESs
      (P<0.05). Moreover, the percentage of reendothelialization was significantly
      higher in ENDs and CD34s than that in SESs or BMSs at both 7 and 14 days
      (P<0.05). There was no difference in the neointima area, percent area stenosis,
      and percentage of reendothelialization in ENDs compared with CD34s. The artery
      injury and the inflammation scores were similar in all groups at both 7 and 14
      days. Our results demonstrate that the performance of ENDs is similar to the
      commercial CD34s, without the disadvantages of CD34s, and both are better than
      SESs and BMSs. ENDs potentially offer an alternative approach to reduce
      restenotic process and enhance reendothelialization after stent implantation. 

PMID- 25945037
TI  - HDACiDB: a database for histone deacetylase inhibitors.
AB  - An histone deacetylase (HDAC) inhibitor database (HDACiDB) was constructed to
      enable rapid access to data relevant to the development of epigenetic modulators
      (HDAC inhibitors [HDACi]), helping bring precision cancer medicine a step closer.
      Thousands of HDACi targeting HDACs are in various stages of development and are
      being tested in clinical trials as monotherapy and in combination with other
      cancer agents. Despite the abundance of HDACi, information resources are limited.
      Tools for in silico experiments on specific HDACi prediction, for designing and
      analyzing the generated data, as well as custom-made specific tools and
      interactive databases, are needed. We have developed an HDACiDB that is a
      composite collection of HDACi and currently comprises 1,445 chemical compounds,
      including 419 natural and 1,026 synthetic ones having the potential to inhibit
      histone deacetylation. Most importantly, it will allow application of Lipinski's
      rule of five drug-likeness and other physicochemical property-based screening of
      the inhibitors. It also provides easy access to information on their source of
      origin, molecular properties, drug likeness, as well as bioavailability with
      relevant references cited. Being the first comprehensive database on HDACi that
      contains all known natural and synthetic HDACi, the HDACiDB may help to improve
      our knowledge concerning the mechanisms of actions of available HDACi and enable
      us to selectively target individual HDAC isoforms and establish a new paradigm
      for intelligent epigenetic cancer drug design. The database is freely available
      on the http://hdacidb.bioinfo.au-kbc.org.in/hdacidb/website. 

PMID- 25945038
TI  - A novel glycyrrhetinic acid-modified oxaliplatin liposome for liver-targeting and
      in vitro/vivo evaluation.
AB  - In this study, oxaliplatin (OX) liposomes surface-modified with glycyrrhetinic
      acid (GA) were developed by the film-dispersion method. Their morphology,
      physical and chemical properties, and in vitro release performance were
      investigated. The transmission electron microscope (TEM) image showed that most
      liposomes were spherical particles with similar size and uniform dispersion. Both
      OX-liposomes and GA-OX-liposomes had an average size of 90 nm. They were
      negatively charged, with zeta potentials of -20.6 and -21.3 mV, respectively, and
      the entrapment efficiency values of both were higher than 94%. In vitro data
      showed that the application of liposomes could prolong the OX release. The
      relatively high correlation coefficient values obtained from analyzing the amount
      of drug released versus the square root of time depicted that release followed
      the Weibull model. No significant changes were observed after the addition of GA
      to the liposomes. In vivo, the relatively long time to reach the maximum plasma
      concentration of OX-liposomes suggested a sustained-release profile of liposomes,
      which was consistent with the results of the in vitro release study. The
      increased area under the curve and maximum plasma concentration of OX-liposomes
      and GA-OX-liposomes demonstrated an increased absorption. The drug concentration
      in tissues indicated that the GA-modified liposomes delivered OX mainly to liver
      after intravenous administration. In addition, no severe signs, such as
      appearance of epithelial necrosis or sloughing of epithelial cells, were detected
      in histology studies. 

PMID- 25945039
TI  - Brentuximab vedotin for treatment of relapsed or refractory malignant lymphoma:
      results of a systematic review and meta-analysis of prospective studies.
AB  - BACKGROUND: Recently, brentuximab vedotin has become a promising therapeutic
      approach for CD30-positive hematological malignancies, but its role in other
      relapsed or refractory malignant lymphoma needs to be proven. Brentuximab vedotin
      was demonstrated effective, but no study has summarized the concrete effect of
      brentuximab vedotin in malignant lymphoma. To truly know the role of brentuximab
      vedotin, we performed a systematic review of the literature and a meta-analysis
      of all known prospective trials, to assess the value of brentuximab vedotin for
      patients with relapsed and refractory malignant lymphoma. METHODS AND MATERIALS:
      This was a systematic review of publications indexed in the PubMed, Embase, the
      Cochrane Central Register of Controlled Trials (CENTRAL), and ISI Web of
      Knowledge performed on February 10, 2015. Six studies, including 302 patients
      were identified. Meta-analyses were carried out to calculate the objective
      response rate (ORR), complete response rate (CRR), and partial response rate
      (PRR) of brentuximab vedotin for malignant lymphoma. RESULTS: In patients with
      malignant lymphoma, ORR was 0.61, CRR was 0.38, and PRR was 0.51. High
      heterogeneity between studies was observed, and funnel plots were not
      symmetrical, which means that publication bias existed. Brentuximab vedotin was
      generally well-tolerated by patients reported in the included studies; adverse
      effects also occurred, but they were considered manageable. CONCLUSION: Our
      analysis revealed a promising benefit of brentuximab vedotin in the treatment of
      relapsed and refractory malignant lymphoma. Larger sample of randomized
      controlled clinical trials are needed in the future.

PMID- 25945041
TI  - Diagnostic and therapeutic path of breast cancer: effectiveness, appropriateness,
      and costs--results from the DOCMa study.
AB  - OBJECTIVE: An increase in breast cancer incidence has been documented in Italy
      and in other countries, and some women decide by themselves to undergo diagnostic
      examinations outside the official screening campaigns. The aim of this paper was
      to analyze - in terms of effectiveness, appropriate access, and related costs -
      the path spontaneously followed by a sample of Italian women for the early
      diagnosis of breast cancer. SUBJECTS AND METHODS: A total of 143 women who
      consecutively referred themselves to the breast cancer outpatient facilities at
      the Sant'Andrea University Hospital in Rome from May to June 2007 were enrolled
      in the study, gave their consent, and were screened according to their individual
      risk factors for breast cancer. The entire diagnostic and therapeutic path
      followed in the previous 2 years by each of them, either at Sant'Andrea or in
      other medical facilities, was reviewed and evaluated in terms of its operative
      efficiency and fair economic value. RESULTS: The subjects' mean age was 47.5
      years (standard deviation 13.6 years); 55% of the women were <50 years old (28%
      <40 years), and were thus not included in the official screening campaigns; 97
      women (70%) were requesting a routine control; and 49% of them had already
      undergone four to seven examinations before the enrollment, although no major
      risk factor was present in 73.5%. After enrollment in the study, nine of the
      patients had surgical interventions performed on them at Sant'Andrea's,
      identifying five invasive carcinomas and two ductal in situ carcinomas and two
      benign lesions. Operative efficiency and fair economic value were found to be
      optimal only in diagnostic/therapeutic paths followed at Sant'Andrea. CONCLUSION:
      The diagnostic path at Sant'Andrea's specialized center for breast cancer
      diagnosis and therapy is characterized by higher operative efficiency and more
      sustainable costs than at general hospitals, outpatient facilities run by local
      health authorities, or private medical centers. This result seems to confirm the
      present tendency to refer high-risk patients for breast cancer directly to breast
      units like the one at Sant'Andrea.

PMID- 25945040
TI  - Evaluation of the protective effects of curcuminoid (curcumin and
      bisdemethoxycurcumin)-loaded liposomes against bone turnover in a cell-based
      model of osteoarthritis.
AB  - Curcumin (Cur) and bisdemethoxycurcumin (BDMC), extracted from Curcuma longa, are
      poorly water-soluble polyphenol compounds that have shown anti-inflammatory
      potential for the treatment of osteoarthritis. To increase cellular uptake of Cur
      and BDMC in bone tissue, soybean phosphatidylcholines were used for liposome
      formulation. In this study, curcuminoid (Cur and BDMC)-loaded liposomes were
      characterized in terms of particle size, encapsulation efficiency, liposome
      stability, and cellular uptake. The results show that there is about 70%
      entrapment efficiency of Cur and BDMC in liposomes and that particle sizes are
      stable after liposome formation. Both types of liposome can inhibit macrophage
      inflammation and osteoclast differential activities. In comparison with free
      drugs (Cur and BDMC), curcuminoid-loaded liposomes were less cytotoxic and
      expressed high cellular uptake of the drugs. Of note is that Cur-loaded liposomes
      can prevent liposome-dependent inhibition of osteoblast differentiation and
      mineralization, but BDMC-loaded liposomes could not. With interleukin (IL)-1beta
      stimulation, curcuminoid-loaded liposomes can successfully downregulate the
      expression of inflammatory markers on osteoblasts, and show a high
      osteoprotegerin (OPG)/receptor activator of nuclear factor kappaB ligand (RANKL)
      ratio to prevent osteoclastogenesis. In the present study, we demonstrated that
      Cur and BDMC can be successfully encapsulated in liposomes and can reduce
      osteoclast activity and maintain osteoblast functions. Therefore, curcuminoid
      loaded liposomes may slow osteoarthritis progression. 

PMID- 25945043
TI  - Voluntary cognitive screening: characteristics of participants in an Asian
      setting.
AB  - BACKGROUND: Mild cognitive impairment (MCI) and dementia are reaching epidemic
      proportions in Asia. Lack of awareness and late presentation are major obstacles
      to early diagnosis and timely intervention. Cognitive screening may be an
      effective method for early detection of dementia in Asia. The purpose of this
      work was to study the characteristics of subjects volunteering for cognitive
      screening in an Asian setting and to determine the prevalence of MCI. METHODS:
      Retrospective and cross-sectional data from community subjects attending a
      screening program from 2008 to 2013 were analyzed. Information on demographics,
      vascular risk factors, subjective symptoms, and cognitive measures were analyzed
      over the 6-year period. RESULTS: Over the 6 years from 2008 to 2013, 1,243
      community subjects voluntarily turned up for cognitive screening (91.2% were
      Chinese, 5.23% were Indian, 1.37% were Malay, and 2.25% were Eurasian). The mean
      age of the participants was 61.3 years and the mean number of years of education
      was 11.0 years. A total of 71.1% of participants were living in public housing,
      59.8% had at least one cardiovascular risk factor, and 56.2% reported subjective
      cognitive symptoms. Over a period of 6 years, no significant change in
      demographic or clinical variables was noted. High cholesterol and hypertension
      were consistently the top two risk factors found in the population screened. In
      total, 17.2% of the total cohort had MCI. Across the 6 years, the proportion with
      MCI and depression was relatively constant. CONCLUSION: A significant proportion
      of participants attending voluntary cognitive screening have MCI. Low level of
      education and presence of vascular risk factors are general predisposing
      characteristics for MCI, and there are more specific factors pertaining to sex
      and employment status.

PMID- 25945042
TI  - Modeling clustered activity increase in amyloid-beta positron emission
      tomographic images with statistical descriptors.
AB  - BACKGROUND: Amyloid-beta (Abeta) imaging with positron emission tomography (PET)
      holds promise for detecting the presence of Abeta plaques in the cortical gray
      matter. Many image analyses focus on regional average measurements of tracer
      activity distribution; however, considerable additional information is available
      in the images. Metrics that describe the statistical properties of images, such
      as the two-point correlation function (S2), have found wide applications in
      astronomy and materials science. S2 provides a detailed characterization of
      spatial patterns in images typically referred to as clustering or flocculence.
      The objective of this study was to translate the two-point correlation method
      into Abeta-PET of the human brain using 11C-Pittsburgh compound B (11C-PiB) to
      characterize longitudinal changes in the tracer distribution that may reflect
      changes in Abeta plaque accumulation. METHODS: We modified the conventional S2
      metric, which is primarily used for binary images and formulated a weighted two
      point correlation function (wS2) to describe nonbinary, real-valued PET images
      with a single statistical function. Using serial 11C-PiB scans, we calculated wS2
      functions from two-dimensional PET images of different cortical regions as well
      as three-dimensional data from the whole brain. The area under the wS2 functions
      was calculated and compared with the mean/median of the standardized uptake value
      ratio (SUVR). For three-dimensional data, we compared the area under the wS2
      curves with the subjects' cerebrospinal fluid measures. RESULTS: Overall, the
      longitudinal changes in wS2 correlated with the increase in mean SUVR but showed
      lower variance. The whole brain results showed a higher inverse correlation
      between the cerebrospinal Abeta and wS2 than between the cerebrospinal Abeta and
      SUVR mean/median. We did not observe any confounding of wS2 by region size or
      injected dose. CONCLUSION: The wS2 detects subtle changes and provides additional
      information about the binding characteristics of radiotracers and Abeta
      accumulation that are difficult to verify with mean SUVR alone.

PMID- 25945044
TI  - Effectiveness of pulmonary rehabilitation in COPD with mild symptoms: a
      systematic review with meta-analyses.
AB  - PURPOSE: Most guidelines recommend pulmonary rehabilitation (PR) for patients
      with chronic obstructive pulmonary disease (COPD) and modified Medical Research
      Council dyspnea scale (mMRC) levels >=2, but the effectiveness of PR in patients
      with less advanced disease is not well established. Our aim was to investigate
      the effects of PR in patients with COPD and mMRC <=1. METHODS: The methodology
      was developed as a part of evidence-based guideline development and is in
      accordance with the principles of the Grading of Recommendations Assessment,
      Development and Evaluation (GRADE) Working Group. We identified randomized
      controlled trials (RCTs) through a systematic, multidatabase literature search
      and selected RCTs comparing the effects of PR with usual care in patients with
      COPD and mMRC <=1. Predefined critical outcomes were health-related quality of
      life (HRQoL), adverse effects and mortality, while walking distance, maximal
      exercise capacity, muscle strength, and dropouts were important outcomes. Two
      authors independently extracted data, assessed trial eligibility and risk of
      bias, and graded the evidence. Meta-analyses were performed when deemed feasible.
      RESULTS: Four RCTs (489 participants) were included. On the basis of moderate
      quality evidence, we found a clinically and statistically significant improvement
      in short-term HRQoL of 4.2 units (95% confidence interval [CI]: [-4.51 to -3.89])
      on St George's Respiratory Questionnaire, but not at the longest follow-up. We
      also found a statistically significant improvement of 25.71 m (95% CI: [15.76
      35.65]) in the 6-minute walk test with PR; however, this improvement was not
      considered clinically relevant. No difference was found for mortality, and
      insufficient data prohibited meta-analysis for muscle strength and maximal
      exercise capacity. No adverse effects were reported. CONCLUSION: We found a
      moderate quality of evidence suggesting a small, significant improvement in short
      term HRQoL and a clinically nonsignificant improvement in walking distance
      following PR in patients with COPD and mild symptoms. This resulted in a weak
      recommendation of routine PR in these patients using the GRADE approach.

PMID- 25945045
TI  - Anti-inflammatory effects of salmeterol/fluticasone propionate 50/250 mcg
      combination therapy in Japanese patients with chronic obstructive pulmonary
      disease.
AB  - PURPOSE: Using sputum neutrophils as the primary measure, and other inflammation
      biomarkers, this study evaluated the anti-inflammatory effects of the combination
      salmeterol 50 mcg and fluticasone propionate 250 mcg (SFC 250) in Japanese
      patients with chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS:
      Patients were treated in a randomized, double-blind, parallel group, placebo
      controlled trial with SFC 250 twice daily (n=26) or placebo (n=26) for 12 weeks.
      At the start and end of treatment, inflammation biomarkers (sputum and serum),
      lung function, and health status (COPD Assessment Test [CAT] questionnaire) were
      measured. RESULTS: Although a numerical decrease in differential neutrophil count
      was observed from baseline, SFC 250 did not significantly reduce sputum
      neutrophils compared with placebo, nor were there significant changes from
      baseline in the other biomarkers (sputum or serum), lung function, or CAT, versus
      placebo. Squamous epithelial cell contamination in some sputum samples rendered
      them unacceptable for analysis, which reduced the sample size to n=19 (SFC 250)
      and n=10 (placebo). However, inclusion of contaminated samples did not affect the
      overall trend of the outcome. Ad hoc bootstrap statistical analysis showed a
      27.9% (SFC 250) and 1.3% (placebo) decrease in sputum neutrophils. Sputum IL-8
      decreased by 43.2% after SFC 250 but increased by 48.3% with placebo. Responder
      analyses showed 42% of patients had >=20% decrease in neutrophils from baseline;
      and 47% of patients had a >=200 pg/mL change in sputum IL-8 following SFC 250
      versus 20% after placebo; both changes are considered clinically relevant.
      CONCLUSION: This study provides additional information about inflammation in
      Japanese COPD patients and is the first to study the anti-inflammatory effects of
      SFC 250 in this context and population. In the primary analysis, SFC 250 did not
      produce significant changes from baseline in sputum neutrophil levels or other
      sputum or serum inflammatory markers compared with placebo. Secondary ad hoc
      statistical analysis showed that SFC 250 reduced the number of sputum neutrophils
      and IL-8 compared with placebo.

PMID- 25945046
TI  - Surface modification of MPEG-b-PCL-based nanoparticles via oxidative self
      polymerization of dopamine for malignant melanoma therapy.
AB  - To enhance the therapeutic effects of chemotherapy on malignant melanoma,
      paclitaxel (PTX)-loaded methoxy poly(ethylene glycol)-b-poly(epsilon
      caprolactone) nanoparticles (MPEG-b-PCL NPs) that had their surfaces modified
      with polydopamine (PTX-loaded MPEG-b-PCL NPs@PDA) were prepared as drug vehicles.
      The block copolymer MPEG-b-PCL was synthesized by ring-opening polymerization and
      characterized by proton nuclear magnetic resonance spectroscopy and gel
      permeation chromatography. The PTX-loaded NPs were prepared by a modified
      nanoprecipitation technique. The PTX-loaded NPs and PTX-loaded NPs@PDA were
      characterized in terms of size and size distribution, zeta potential, surface
      morphology, drug encapsulation efficiency, and drug release. Confocal laser
      scanning microscopy showed that coumarin-6-loaded NPs@PDA could be internalized
      by human melanoma cell line A875 cells. The cellular uptake efficiency of NPs was
      greatly enhanced after PDA modification. The antitumor efficacy of the PTX-loaded
      NPs@PDA was investigated in vitro by the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay and in vivo by a xenograft tumor model.
      The PTX-loaded NPs@PDA could significantly inhibit tumor growth compared to
      Taxol((r)) and precursor PTX-loaded NPs. All the results suggested that the PTX
      loaded MPEG-b-PCL NPs that had their surfaces modified with PDA are promising
      nanocarriers for malignant melanoma therapy. 

PMID- 25945047
TI  - Poly(d,l-lactide-co-glycolide)-chitosan composite particles for the treatment of
      lung cancer.
AB  - Tumor heterogeneity makes combination chemotherapy one of the preferred modes of
      treatment regimens. In this work, sequential exposure of two anticancer agents,
      paclitaxel (Tx) followed by topotecan (TPT), was shown to have a synergistic
      effect on non-small cell lung cancer (NSCLC) cell line, NCI-H460. In order to
      improve patient compliance, the aforementioned concept was translated into a drug
      delivery system comprising of poly(d,l-lactide-co-glycolide) (PLGA)-chitosan
      composite particles. TPT-containing chitosan micro-/nanoparticles were prepared
      by the facile technique of electrospraying and encapsulated within PLGA
      microparticles using emulsion-solvent evaporation technique for delayed release
      of TPT. The formulation containing Tx- and TPT-loaded composite particles
      demonstrated synergism when exposed to NCI-H460 cellular aggregates (tumoroids)
      generated in vitro. Overall, the results of this study demonstrated the potential
      of the formulation containing Tx and PLGA-chitosan (TPT-loaded) composite
      particles for the treatment of lung cancer. 

PMID- 25945048
TI  - Some inferences from in vivo experiments with metal and metal oxide
      nanoparticles: the pulmonary phagocytosis response, subchronic systemic toxicity
      and genotoxicity, regulatory proposals, searching for bioprotectors (a self
      overview).
AB  - The purpose of this paper is to overview and summarize previously published
      results of our experiments on white rats exposed to either a single intratracheal
      instillation or repeated intraperitoneal injections of silver, gold, iron oxide,
      copper oxide, nickel oxide, and manganese oxide nanoparticles (NPs) in stable
      water suspensions without any chemical additives. Based on these results and some
      corroborating data of other researchers we maintain that these NPs are much more
      noxious on both cellular and systemic levels as compared with their 1 MUm or even
      submicron counterparts. However, within the nanometer range the dependence of
      systemic toxicity on particle size is intricate and non-unique due to complex and
      often contra-directional relationships between the intrinsic biological
      aggressiveness of the specific NPs, on the one hand, and complex mechanisms that
      control their biokinetics, on the other. Our data testify to the high activity of
      the pulmonary phagocytosis of NPs deposited in airways. This fact suggests that
      safe levels of exposure to airborne NPs are possible in principle. However, there
      are no reliable foundations for establishing different permissible exposure
      levels for particles of different size within the nanometric range. For workroom
      air, such permissible exposure levels of metallic NP can be proposed at this
      stage, even if tentatively, based on a sufficiently conservative approach of
      decreasing approximately tenfold the exposure limits officially established for
      respective micro-scale industrial aerosols. It was shown that against the
      background of adequately composed combinations of some bioactive agents
      (comprising pectin, multivitamin-multimineral preparations, some amino acids, and
      omega-3 polyunsaturated fatty acid) the systemic toxicity and even genotoxicity
      of metallic NPs could be markedly attenuated. Therefore we believe that, along
      with decreasing NP-exposures, enhancing organisms' resistance to their adverse
      action with the help of such bioprotectors can prove an efficient auxiliary tool
      of health risk management in occupations connected with them. 

PMID- 25945050
TI  - CD44(+)/CD24(-) breast cancer cells exhibit phenotypic reversion in three
      dimensional self-assembling peptide RADA16 nanofiber scaffold.
AB  - BACKGROUND: Self-assembling peptide nanofiber scaffolds have been shown to be a
      permissive biological material for tissue repair, cell proliferation,
      differentiation, etc. Recently, a subpopulation (CD44(+)/CD24(-)) of breast
      cancer cells has been reported to have stem/progenitor cell properties. The aim
      of this study was to investigate whether this subpopulation of cancer cells have
      different phenotypes in self-assembling COCH3-RADARADARADARADA-CONH2 (RADA16)
      peptide nanofiber scaffold compared with Matrigel((r)) (BD Biosciences, Two Oak
      Park, Bedford, MA, USA) and collagen I. METHODS: CD44 and CD24 expression was
      determined by flow cytometry. Cell proliferation was measured by 5-bromo-2'
      deoxyuridine assay and DNA content measurement. Immunostaining was used to
      indicate the morphologies of cells in three-dimensional (3D) cultures of
      different scaffolds and the localization of beta-catenin in the colonies. Western
      blot was used to determine the expression of signaling proteins. In vitro
      migration assay and inoculation into nude mice were used to evaluate invasion and
      tumorigenesis in vivo. RESULTS: The breast cancer cell line MDA-MB-435S contained
      a high percentage (>99%) of CD44(+)/CD24(-) cells, which exhibited phenotypic
      reversion in 3D RADA16 nanofiber scaffold compared with collagen I and Matrigel.
      The newly formed reverted acini-like colonies reassembled a basement membrane and
      reorganized their cytoskeletons. At the same time, cells cultured and embedded in
      RADA16 peptide scaffold exhibited growth arrest. Also, they exhibited different
      migration potential, which links their migration ability with their cellular
      morphology. Consistent with studies in vitro, the in vivo tumor formation assay
      further supported of the functional changes caused by the reversion in 3D RADA16
      culture. Expression levels of intercellular surface adhesion molecule-1 were
      upregulated in cells cultured in RADA16 scaffolds, and the NF-kappa B inhibitor
      pyrrolidine dithiocarbamate could inhibit RADA16-induced upregulation of
      intercellular surface adhesion molecule-1 and the phenotype reversion of MDA-MB
      453S cells. CONCLUSION: Culturing a CD44(+)/CD24(-)-enriched breast cancer cell
      population in 3D RADA16 peptide nanofiber scaffold led to a significant
      phenotypic reversion compared with Matrigel and collagen I.

PMID- 25945049
TI  - Pharmacokinetics of quercetin-loaded nanodroplets with ultrasound activation and
      their use for bioimaging.
AB  - Bubble formulations have both diagnostic and therapeutic applications. However,
      research on nanobubbles/nanodroplets remains in the initial stages. In this
      study, a nanodroplet formulation was prepared and loaded with a novel class of
      chemotherapeutic drug, ie, quercetin, to observe its pharmacokinetic properties
      and ultrasonic bioimaging of specific sites, namely the abdominal vein and
      bladder. Four parallel groups were designed to investigate the effects of
      ultrasound and nanodroplets on the pharmacokinetics of quercetin. These groups
      were quercetin alone, quercetin triggered with ultrasound, quercetin-encapsulated
      in nanodroplets, and quercetin encapsulated in nanodroplets triggered with
      ultrasound. Spherical vesicles with a mean diameter of 280 nm were formed, and
      quercetin was completely encapsulated within. In vivo ultrasonic imaging
      confirmed that the nanodroplets could be treated by ultrasound. The results
      indicate that the initial 5-minute serum concentration, area under the
      concentration-time curve, elimination half-life, and clearance of quercetin were
      significantly enhanced by nanodroplets with or without ultrasound. 

PMID- 25945051
TI  - Characterization of nanostructured ureteral stent with gradient degradation in a
      porcine model.
AB  - A tubular poly(epsilon-caprolactone) (PCL)/poly(lactide-co-glycolide) (PLGA)
      ureteral stent composed of nanofibers with micropores was fabricated by double
      needle electrospinning. The stent was ureteroscopically inserted into six
      Changbai pigs, and the commercial polyurethane Shagong((r)) stent was inserted
      into four pigs as control. Intravenous pyelography revealed that the PCL/PLGA
      stent gradually degraded from the distal end to proximal terminal, and all stents
      were completely degraded at 10 weeks post-insertion. No significant difference
      was observed in hydronephrosis severity between the two groups. The levels of
      serum creatinine and urine pH remained similar throughout the study in the two
      groups, but the number of white blood cells in the urine was significantly higher
      in the Shagong((r)) stent group. On Day 70, histological evaluation indicated
      equivalent histological severity scores in the middle and distal ureter sections
      and bladder in the two groups. However, the PCL/PLGA stent-implanted pigs had
      significantly lower mean severity scores in the kidney and proximal ureter sites.
      These data revealed that the PCL/PLGA stent degraded in a controlled manner, did
      not induce obstruction, and had a lower urothelial impact in comparison to the
      Shagong((r)) stent, indicating that the stent exhibited great potential for
      clinical application. 

PMID- 25945052
TI  - Comorbid personality disorders among patients with depression.
AB  - PURPOSE: To investigate the personality disorders (PDs) diagnosed in patients
      with depressive disorders. MATERIAL AND METHODS: This study included a cross
      sectional analysis, and was an extension of the Thai Study of Affective Disorder
      (THAISAD) project. Eighty-five outpatients with depressive disorders were
      interviewed using the Mini International Neuropsychiatric Inventory to assess for
      depression, in accordance with the Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition, Text Revision and using the Thai version of the
      Structured Clinical Interview for PDs to assess for PD. RESULTS: Seventy-seven
      percent of the patients had at least one PD, 40% had one PD and 60% had two or
      more PDs (mixed cluster). The most common PDs found were borderline PD (20%) and
      obsessive-compulsive PD (10.6%), while the occurrence of avoidant PD was low when
      compared to the findings of previous, related studies. Among the mixed cluster,
      cluster A combined with cluster C was the common mix. Both dysthymic disorder and
      double depression were found to have a higher proportion of PDs than major
      depressive disorder (85.7% versus 76.1%). Dependent PD was found to be less
      common in this study than in previous studies, including those carried out in
      Asia. CONCLUSION: The prevalence of PDs among those with depressive disorder
      varied, and only borderline PD seems to be consistently high within and across
      cultures. Mixed cluster plays a prominent role in depression, so more attention
      should be paid to patients in this category.

PMID- 25945053
TI  - Factors associated with poor discharge status in patients with status epilepticus
      at Khon Kaen Hospital.
AB  - BACKGROUND: Status epilepticus (SE) is a serious neurological condition and has
      high a mortality rate. Data on importance of factors associated with poor
      outcomes in Asian or Thai populations are limited. METHODS: Adult patients
      diagnosed as SE at Khon Kaen Hospital, Thailand from October 1, 2010 to September
      30, 2012 were enrolled. Patients were categorized as good or poor outcomes at
      discharge. Good outcomes were defined by improvement at discharge and absence of
      neurological deficits, while poor outcomes were defined by: not being improved at
      discharge; being discharged against advice; death; or presence of a neurological
      deficit. Clinical factors were compared between both groups. RESULTS: During the
      study period, there were 211 patients diagnosed as SE. Of those, 130 patients
      were male (61.61%). The mean age of all patients was 53.28 years. Acute stroke
      was the most common cause of SE in 33 patients (15.64%). At discharge, there were
      91 patients (43.13%) who had poor outcomes. Only initial plasma glucose levels
      were significantly associated with poor outcomes with an adjusted odds ratio of
      1.012 (95% confidence interval of 1.003 and 1.021). CONCLUSION: Initial plasma
      glucose is associated with poor discharge status in patients with SE.

PMID- 25945054
TI  - Erratum: Travel advice for the immunocompromised traveler: prophylaxis,
      vaccination, and other preventive measures [Corrigendum].
AB  - [This corrects the article on p. 217 in vol. 11, PMID: 25709464.]. 

PMID- 25945055
TI  - Artesunate inhibits the growth and induces apoptosis of human gastric cancer
      cells by downregulating COX-2.
AB  - Artesunate, a derivative of artemisinin isolated from Artemisia annua L., has
      been traditionally used to treat malaria, and artesunate has demonstrated
      cytotoxic effects against a variety of cancer cells. However, there is little
      available information about the antitumor effects of artesunate on human gastric
      cancer cells. In the present study, we investigated the antitumor effect of
      artesunate on human gastric cancer cells and whether its antitumor effect is
      associated with reduction in COX-2 expression. The effects of artesunate on the
      growth and apoptosis of gastric cancer cells were investigated by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow
      cytometric analysis of annexin V-fluorescein isothiocyanate/propidium iodide
      staining, rhodamine 123 staining, and Western blot analysis. Results indicate
      that artesunate exhibits antiproliferative effects and apoptosis-inducing
      activities. Artesunate markedly inhibited gastric cancer cell proliferation in a
      time- and dose-dependent manner and induced apoptosis in gastric cancer cells a
      dose-dependent manner, which was associated with a reduction in COX-2 expression.
      Treatment with the selective COX-2 inhibitor celecoxib, or transient transfection
      of gastric cancer cells with COX-2 siRNA, also inhibited cell proliferation and
      induced apoptosis. Furthermore, the treatment with artesunate promoted the
      expression of proapoptotic factor Bax and suppressed the expression of
      antiapoptotic factor Bcl-2. In addition, caspase-3 and caspase-9 were activated,
      and artesunate induced loss of mitochondrial membrane potential, suggesting that
      the apoptosis is mediated by mitochondrial pathways. These results demonstrate
      that artesunate has an effect on anti-gastric cancer cells. One of the antitumor
      mechanisms of artesunate may be that its inhibition of COX-2 led to reduced
      proliferation and induction of apoptosis, connected with mitochondrial
      dysfunction. Artesunate might be a potential therapeutic agent for gastric
      cancer. 

PMID- 25945056
TI  - Outcome of surgical resection for brain metastases and radical treatment of the
      primary tumor in Chinese non-small-cell lung cancer patients.
AB  - PURPOSE: Brain metastasis is the most common complication of brain cancer;
      nevertheless, primary lung cancer accounts for approximately 20%-40% of brain
      metastases cases. Surgical resection is the preferred treatment for brain
      metastases. However, no studies have reported the outcome of surgical resection
      of brain metastases from non-small-cell lung cancer (NSCLC) in the People's
      Republic of China. Moreover, the optimal treatment for primary NSCLC in patients
      with synchronous brain metastases is hitherto controversial. PATIENTS AND
      METHODS: We retrospectively analyzed the cases of NSCLC patients with brain
      metastases who underwent neurosurgical resection at the Sun Yat-sen University
      Cancer Center, and assessed the efficacy of surgical resection and the necessity
      of aggressive treatment for primary NSCLC in synchronous brain metastases
      patients. RESULTS: A total of 62 patients, including 47 men and 15 women, with
      brain metastases from NSCLC were enrolled in the study. The median age at the
      time of craniotomy was 54 years (range 29-76 years). At the final follow-up
      evaluation, 50 patients had died. The median OS time was 15.1 months, and the
      survival rates were 70% and 37% at 1 and 2 years, respectively. The median OS
      time of synchronous brain metastases patients was 12.5 months. Univariate
      analysis revealed that radical treatment of primary NSCLC was positively
      correlated with survival, and it was an independent prognostic factor in the
      multivariate analysis. CONCLUSION: Surgical resection is an effective treatment
      for brain metastases. Besides craniotomy, radical therapy is necessary for the
      management of primary NSCLC in patients with synchronous brain metastases.

PMID- 25945057
TI  - Relationship between single-nucleotide polymorphism of matrix metalloproteinase-2
      gene and colorectal cancer and gastric cancer susceptibility: a meta-analysis.
AB  - BACKGROUND: Recently, the published data on the association between matrix
      metalloproteinase-2 (MMP-2) (C-1306T) polymorphism and colorectal cancer (CRC)
      and gastric cancer (GC) (gastrointestinal cancer) risk remained controversial.
      The aim of this study is to investigate the relationship between the risk of CRC
      and GC and single-nucleotide polymorphism of MMP-2(C-1306T). METHODS: Medline,
      Embase, Science Citation Index, and PubMed were thoroughly searched to identify
      relevant studies. Odds ratio (OR) with 95% confidence interval (CI) was used to
      assess the strength of the association. RESULTS: We performed a meta-analysis of
      14 studies including 642 cases and 692 controls for CRC and 1,936 cases and 3,490
      controls for GC. The result indicates that there is significant relationship
      between MMP-2(C-1306T) polymorphism and CRC risk in recessive model and
      codominant model (TT vs CC/CT: OR: 2.39, 95% CI: 1.30-4.37, P=0.005; TT vs CC:
      OR: 2.36, 95% CI: 1.29-4.34, P=0.006). In subgroup analysis according to
      ethnicity, significant associations were found in Caucasians (TT vs CC/CT: OR:
      2.87, 95% CI: 1.43-5.78, P=0.003; TT vs CC: OR: 2.86, 95% CI: 1.41-5.80,
      P=0.003), but we did not find significant evidence with GC in all genetic models,
      and in stratified analysis according to ethnicity, no significant risk was found
      in the subgroup too. CONCLUSION: This meta-analysis considered that the MMP-2(C
      1306T) polymorphism is a risk factor for CRC susceptibility, especially in
      Caucasians, but it does not support any relationship to GC, and further studies
      are needed to explore the association.

PMID- 25945058
TI  - Enzalutamide for patients with metastatic castration-resistant prostate cancer.
AB  - OBJECTIVE: To review and evaluate current literature on the US Food and Drug
      Administration (FDA)-approved drug enzalutamide (XTANDI((r))) in metastatic
      castration-resistant prostate cancer. DATA SOURCES: Literature search was done
      through PubMed using the terms enzalutamide, MDV3100, abiraterone, and castration
      resistant prostate cancer. Data from FDA product labels were also used. STUDY
      SELECTION AND DATA EXTRACTION: Recent and relevant studies were included in the
      review. Collected clinical trials were screened and evaluated. DATA SYNTHESIS:
      Enzalutamide is an androgen receptor (AR) inhibitor with high selectivity and
      affinity to the AR. It was approved by the FDA to treat metastatic castration
      resistant prostate cancer in patients previously treated with docetaxel, after a
      Phase III trial (AFFIRM) that showed a 4.8-month survival benefit in this
      population. Recently, the FDA expanded the approval of enzalutamide as first-line
      therapy for metastatic castration-resistant prostate cancer (mCRPC) who did not
      receive chemotherapy. Moreover, enzalutamide is shown to be associated with an
      acceptable safety profile. CONCLUSION: Enzalutamide has been shown to be both
      safe and effective in improving overall survival in metastatic castration
      resistant prostate cancer postchemotherapy with docetaxel and as a first line
      treatment before initiation of chemotherapy. However, additional studies and head
      to-head trials are needed.

PMID- 25945059
TI  - Synergistic inhibition of colon carcinoma cell growth by Hedgehog-Gli1 inhibitor
      arsenic trioxide and phosphoinositide 3-kinase inhibitor LY294002.
AB  - The Hedgehog (Hh) signaling pathway not only plays important roles in
      embryogenesis and adult tissue homeostasis, but also in tumorigenesis. Aberrant
      Hh pathway activation has been reported in a variety of malignant tumors
      including colon carcinoma. Here, we sought to investigate the regulation of the
      Hh pathway transcription factor Gli1 by arsenic trioxide and phosphoinositide 3
      kinase (PI3K) inhibitor LY294002 in colon carcinoma cells. We transfected cells
      with siGli1 and observed a significant reduction of Gli1 expression in HCT116 and
      HT29 cells, which was confirmed by quantitative real-time polymerase chain
      reaction and Western blots. Knocking down endogenous Gli1 reduced colon carcinoma
      cell viability through inducing cell apoptosis. Similarly, knocking down Gli2
      using short interfering RNA impaired colon carcinoma cell growth in vitro. To
      elucidate the regulation of Gli1 expression, we found that both Gli inhibitor
      arsenic trioxide and PI3K inhibitor LY294002 significantly reduced Gli1 protein
      expression and colon carcinoma cell proliferation. Arsenic trioxide treatment
      also reduced Gli1 downstream target gene expression, such as Bcl2 and CCND1. More
      importantly, the inhibition of Hedgehog-Gli1 by arsenic trioxide showed
      synergistic anticancer effect with the PI3K inhibitor LY294002 in colon carcinoma
      cells. Our findings suggest that the Hh pathway transcription factor Gli1 is
      involved in the regulation of colon carcinoma cell viability. Inhibition of
      Hedgehog-Gli1 expression by arsenic trioxide and PI3K inhibitor synergistically
      reduces colon cancer cell proliferation, indicating that they could be used as an
      effective anti-colon cancer combination therapy. 

PMID- 25945060
TI  - Novel targeted therapies for resistant ALK-rearranged non-small-cell lung cancer:
      ceritinib and beyond.
AB  - Lung cancer is the leading cause of cancer-related mortality in both sexes,
      accounting for over one quarter of cancer deaths. Non-small-cell lung cancer
      (NSCLC) comprises 85%-90% of lung cancer diagnoses and despite advances in
      multimodality therapies, 5-year survival rates remain dismal with a median
      survival for patients with metastatic disease of 1 year. The positive outcomes of
      targeted therapies against the kinase domain of epidermal growth factor receptor
      in NSCLC triggered consistent efforts to identify the so-called driver mutations
      as other potential targets. Anaplastic large-cell kinase (ALK) gene
      rearrangements were identified and targeted resulting in promising response rates
      in early studies. Unfortunately, most of the patients treated with crizotinib,
      the first-generation ALK inhibitor, progressed within 9 months. Ceritinib is a
      second-generation ALK inhibitor that has demonstrated activity in crizotinib
      resistant patients, becoming a promising treatment option in this population.
      Furthermore, additional novel ALK inhibitors and agents targeting alternative
      pathways have been recruited to rechallenge this evasive disease post-crizotinib
      resistance. 

PMID- 25945061
TI  - Comparison of single-agent chemotherapy and targeted therapy to first-line
      treatment in patients aged 80 years and older with advanced non-small-cell lung
      cancer.
AB  - PURPOSE: The aim of this study was to compare single-agent chemotherapy with
      targeted therapy in initial treatment and to explore a better choice of treatment
      for patients aged 80 years and older with advanced non-small-cell lung cancer
      (NSCLC). PATIENTS AND METHODS: A retrospective chart review was conducted for 136
      patients aged 80 years and older who were cytopathologically diagnosed and staged
      as advanced (stage IIIB or IV) NSCLC. The patient population was divided into two
      treatment groups: 78 patients were allocated to the chemotherapy group (group A,
      pemetrexed or gemcitabine or docetaxel as a single agent), and 60 patients were
      allocated to another group and received epidermal growth factor-receptor tyrosine
      kinase inhibitors (group B, erlotinib or gefitinib as a single agent). The
      primary end points were overall survival (OS) and progression-free survival
      (PFS), and the secondary end points were response rate, disease-control rate,
      safety, and quality of life. RESULTS: In group A and group B, respectively, the
      median PFS was 2 versus 4 months (P=0.013), and the median OS was 8 versus 16
      months (P=0.025). The 1- and 2-year survival rates of the two groups were 23.7%
      (group A, 18 of 76) versus 76.7% (group B, 46 of 60) and 13.2% (group A, ten of
      76) versus 10% (group B, six of 60), respectively. The response rate and disease
      control rate were 28.9% versus 36.7% (P=0.39) and 57.9% versus 76.7% (P=0.022) in
      group A and group B, respectively. CONCLUSION: Elders aged 80 years and over with
      advanced NSCLC in group B had longer PFS and OS compared with group A. It was
      well tolerated in group B because of the mild adverse effects. Targeted therapy
      can be considered primarily for patients aged 80 years and older with advanced
      NSCLC who cannot tolerate chemotherapy or radiotherapy.

PMID- 25945062
TI  - Incorporating ulipristal acetate in the care of symptomatic uterine fibroids: a
      Canadian cost-utility analysis of pharmacotherapy management.
AB  - OBJECTIVE: To present a Canadian economic evaluation on the cost-utility of
      ulipristal acetate (5 mg orally daily) compared to leuprolide acetate (3.75 mg
      intramuscular monthly) in the treatment of moderate-to-severe symptoms of uterine
      fibroids in women eligible for surgery. METHODS: A probabilistic decision tree
      was constructed to model the pre-operative pharmacological management of uterine
      fibroids under the primary perspective of the Ontario public payer. The model
      parameterized data from clinical trials, observational studies, and public
      costing databases. The outcome measure was the incremental cost-utility ratio.
      Uncertainty in the model was explored through sensitivity and scenario analyses.
      RESULTS: Ulipristal was associated with faster control of excessive menstrual
      bleeding, fewer symptoms of hot flashes and lower health care resource
      consumption. The ulipristal strategy dominated leuprolide as it provided patients
      with more quality-adjusted life years (0.177 versus 0.165) at a lower cost
      ($1,273 versus $1,366). Across a range of sensitivity analyses, the results
      remained robust except to the dose of the comparator drug. If leuprolide was
      administered at 11.25 mg, once every 3 months, the expected cost for the
      leuprolide strategy would decline and the associated incremental cost-utility
      ratio for ulipristal would be $168/quality-adjusted life year. CONCLUSION:
      Ulipristal offers a unique opportunity to effectively and rapidly control
      menstrual bleeding in patients with uterine fibroids; thereby improving their
      quality of life while minimizing the probability of moderate-to-severe hot
      flashes that are common with leuprolide. The current economic analysis suggests
      that ulipristal remains the dominant strategy across extensive sensitivity
      analyses.

PMID- 25945063
TI  - Itolizumab - a humanized anti-CD6 monoclonal antibody with a better side effects
      profile for the treatment of psoriasis.
AB  - Management of psoriasis is a challenge to the treating physician. The chronic
      inflammatory state of psoriasis with exacerbations and remissions necessitate "on
      and-off" treatment schedules. The safety profiles of drugs and tolerability
      issues for patients are important factors to be considered during treatment.
      Various biological agents targeting T-cells and the inflammatory cytokines are
      available for systemic treatment of psoriasis. However, major causes of concern
      while using these drugs are risk of susceptibility to infection and development
      of anti-drug antibodies, which will affect the pharmacokinetic properties,
      efficacy, and safety profile of the drug. Itolizumab, a humanized anti-CD6
      monoclonal antibody, is a new molecule that acts by immunomodulating the CD6
      molecule. CD6 is a co-stimulatory molecule required for optimal T-cell
      stimulation by the antigen-presenting cells. This step is crucial in T-cell
      proliferation to form Th1 and Th17 cells, which play a major role in the
      pathogenesis of psoriasis. This article deals with the properties of Itolizumab
      and its role in the treatment of psoriasis. Based on the available published
      data, Itolizumab seems to have a better adverse effects profile and at the same
      time comparatively less efficacy when compared to other biological agents
      available for treating psoriasis. Larger studies with longer duration are
      required to clearly depict the long-term side effects profile. 

PMID- 25945064
TI  - Liver abscess caused by Salmonella choleraesuis.
AB  - A 65-year-old man with long-term alcohol abuse presented with intermittent fever.
      Abdominal computed tomography revealed multiple masses. Abscess blood and pus
      cultures conducted after percutaneous catheter drainage with pigtail catheters
      yielded Salmonella choleraesuis. Antibiotic treatment with meropenem was started
      using multiple catheters in the liver. Drainage catheters in different locations
      were exchanged several times with larger-bored catheters. After septicemia was
      detected, abscesses spread to the peritoneal cavity. Pleural complications
      developed. Antibiotic treatment, with careful drainage guided by ultrasound or
      computed tomography, controlled the abscesses and complications. This report
      describes the difficult clinical course and treatment of a liver abscess from S.
      choleraesuis. 

PMID- 25945065
TI  - Tactile, thermal, and electrical thresholds in patients with and without phantom
      limb pain after traumatic lower limb amputation.
AB  - PURPOSE: To examine whether there is central sensitization in patients with
      phantom limb pain (PLP) after traumatic limb amputation. METHODS: Seventeen
      patients after unilateral lower limb amputation secondary to trauma were
      enrolled. Ten patients had chronic PLP, while the other seven patients had no
      PLP. Tactile-sensation threshold, cold- and warm-sensation thresholds, cold- and
      heat-pain thresholds, electrical-sensation threshold (EST), and electrical-pain
      threshold on the distal residual limb and the symmetrical site on the sound limb
      were measured in all tested patients. Their thresholds were compared within the
      PLP and non-PLP group, and between the groups. RESULTS: The novel findings
      included: 1) electrical-pain threshold was only decreased in the sound limb in
      the PLP group and there was no difference between two limbs in the non-PLP group,
      suggesting central sensitization in patients with PLP; and 2) EST was increased
      on the affected limb as compared to the sound limb within the PLP group, but
      there were no significant differences in EST between the PLP and non-PLP group.
      There were in general no significant differences in other tested thresholds
      within the groups and between groups. CONCLUSION: Our results demonstrate central
      sensitization in the patients with PLP after traumatic limb amputation.

PMID- 25945067
TI  - Oxaliplatin-based first-line chemotherapy is associated with improved overall
      survival compared to first-line treatment with irinotecan-based chemotherapy in
      patients with metastatic colorectal cancer - Results from a prospective cohort
      study.
AB  - PURPOSE: Several randomized trials investigating the preferable first-line
      combination chemotherapy regimen for metastatic colorectal cancer have shown
      inconsistent findings. Because a substantial number of patients are still being
      treated with "chemo-only" first-line therapies without targeted agents, we
      compared overall survival (OS) of patients treated in routine practice with
      oxaliplatin-fluoropyrimidine and irinotecan-fluoropyrimidine. PATIENTS AND
      METHODS: Using the database of the Tumor Registry Colorectal Cancer, we
      identified 605 patients with metastatic colorectal cancer who received first-line
      fluoropyrimidine combination chemotherapy with either oxaliplatin (n=430) or
      irinotecan (n=175). The Tumor Registry Colorectal Cancer is a cohort study that
      prospectively documents treatment of colorectal cancer by office-based medical
      oncologists in Germany and has recruited over 5,000 patients. OS was estimated
      using the Kaplan-Meier method, and a multivariate Cox proportional hazard model
      was used to adjust for potentially confounding variables. RESULTS: Median OS was
      26.8 (95% confidence interval [CI] 22.4-31.9) months with an oxaliplatin
      fluoropyrimidine combination and 18.3 (95% CI 15.1-23.2) months with irinotecan
      fluoropyrimidine first-line "chemo-only" therapy. Median progression-free
      survival was 9.0 (8.1-10.2) and 7.9 (7.2-10.2) months, respectively. The
      difference in OS was confirmed if analysis was restricted to patients with
      synchronous metastases (no prior treatment). Among other variables, proportion of
      patients receiving any second-line therapy did not differ between groups.
      Oxaliplatin-based first-line therapy was associated with improved OS in
      multivariate analysis adjusted for potentially confounding variables (hazard
      ratio 0.678, 95% CI 0.510-0.901, P=0.007). CONCLUSION: In clinical routine
      practice, first-line treatment with oxaliplatin-fluoropyrimidine combination
      chemotherapy compared to irinotecan-fluoropyrimidine combination is associated
      with improved survival in patients with metastatic colorectal cancer, independent
      of all examined potentially confounding factors.

PMID- 25945068
TI  - Acute orbital apex syndrome and rhino-orbito-cerebral mucormycosis.
AB  - PURPOSE: To demonstrate the successful clinical identification and management of
      rhino-orbital mucormycosis, a fungal infection with a high mortality rate.
      PATIENTS AND METHODS: A diabetic male patient with a headache and orbital apex
      syndrome in the right eye was examined using computed tomography (CT) and
      magnetic resonance imaging (MRI) for a possible fungal infection. Endoscopic
      surgical resection was performed and a pathology sample was taken. Specimens were
      prepared with Gomori methenamine silver and hematoxylin and eosin staining. The
      patient was treated with liposomal amphotericin B 400 mg daily, followed by
      posaconazole 400 mg twice daily. RESULTS: CT and MRI revealed a mass of the right
      sphenoid spreading into the orbit, indicative of a fungal infection. The biopsy
      confirmed the diagnosis of mucormycosis. Complete recovery of eyelid and
      oculomotor function was achieved after 10 months of treatment, although the
      patient continues to suffer from irreversible blindness in the right eye due to
      optic nerve atrophy. He has been without signs or symptoms of recurrence.
      CONCLUSION: Patients with rhino-orbito-cerebral mucormycosis need extensive
      surgical and medical treatment to maximize outcomes. Success requires
      multidisciplinary management.

PMID- 25945066
TI  - Cushing's syndrome: epidemiology and developments in disease management.
AB  - Cushing's syndrome is a rare disorder resulting from prolonged exposure to excess
      glucocorticoids. Early diagnosis and treatment of Cushing's syndrome is
      associated with a decrease in morbidity and mortality. Clinical presentation can
      be highly variable, and establishing the diagnosis can often be difficult.
      Surgery (resection of the pituitary or ectopic source of adrenocorticotropic
      hormone, or unilateral or bilateral adrenalectomy) remains the optimal treatment
      in all forms of Cushing's syndrome, but may not always lead to remission. Medical
      therapy (steroidogenesis inhibitors, agents that decrease adrenocorticotropic
      hormone levels or glucocorticoid receptor antagonists) and pituitary radiotherapy
      may be needed as an adjunct. A multidisciplinary approach, long-term follow-up,
      and treatment modalities customized to each individual are essential for optimal
      control of hypercortisolemia and management of comorbidities. 

PMID- 25945069
TI  - Pharmacokinetic equivalence study of two formulations of the anticonvulsant
      pregabalin.
AB  - PURPOSE: The present study was conducted to evaluate whether the bioavailability
      of pregabalin capsules 150 mg manufactured by PT Dexa Medica was equivalent to
      the reference formulation. METHODS: This was a randomized, open-label, two
      period, two-sequence, and crossover study under fasting condition, with a 1-week
      washout period. Plasma concentrations of pregabalin from 20 subjects were
      determined by using a validated liquid chromatography with tandem mass
      spectrometry (LC-MS/MS) detection method. Pharmacokinetic parameters assessed in
      this study were: area under the plasma concentration-time curve from time zero to
      last observed quantifiable concentration (AUC0-t), area under the plasma
      concentration-time curve from time zero to infinity (AUC0-infinity), maximum
      plasma concentration (Cmax), time to maximum plasma concentration (tmax), and
      terminal half-life (t1/2). The 90% confidence intervals (CIs) for the geometric
      mean ratios of test formulation/reference formulation were calculated for the AUC
      and Cmax parameters; while tmax difference was analyzed nonparametrically on the
      original data using the Wilcoxon matched-pairs test, and t1/2 difference was
      analyzed using Student's paired t-test. RESULTS: The mean (standard deviation
      [SD]) AUC0-t, AUC0-infinity, Cmax, and t1/2 of pregabalin from the test
      formulation were 27,845.86 (4,508.27) ng . h/mL, 28,311.70 (4,790.55) ng . h/mL,
      3,999.71 (801.52) ng/mL, and 5.66 (1.20) hours, respectively; while the mean (SD)
      AUC0-t, AUC0-infinity,Cmax, and t1/2 of pregabalin from the reference formulation
      were 27,398.12 (4,266.28) ng . h/mL, 27,904.24 (4,507.31) ng . h/mL, 3,849.50
      (814.50) ng/mL, and 5.87 (1.25) hours, respectively. The median (range) tmax of
      pregabalin from the test formulation and reference formulation was 1.00 (0.67
      2.00) hours and 1.00 (0.67-3.00) hours, respectively. The 90% CIs for the
      geometric mean ratios of test formulation/reference formulation for pregabalin
      were 101.54% (98.75%-104.41%) for AUC0-t, 101.35% (98.66%-104.11%) for AUC0
      infinity, and 104.19% (98.75%-109.93%) for Cmax. CONCLUSION: The study concluded
      that the two formulations of pregabalin capsules studied were bioequivalent.

PMID- 25945071
TI  - Occurrence of anti-D alloantibodies among pregnant women in Kasese District,
      Western Uganda.
AB  - OBJECTIVES: This study was undertaken to determine the distribution of ABO/RhD
      (rhesus D antigen) blood phenotypes, prevalence of anti-D alloantibodies, and the
      risk factors for alloimmunization among pregnant women in Kasese District,
      Western Uganda. MATERIALS AND METHODS: Ethylenediamine tetraacetic acid
      containing plasma samples and serum samples were taken from pregnant women
      attending the antenatal clinic. The blood groups were identified using the
      microplate grouping method, while the presence of anti-D alloantibodies was
      detected by the indirect antiglobulin test (IAT). Data were also collected from
      the pregnant women on the risk factors associated with anti-D alloantibody
      formation. RESULTS: Among the 726 participants, the blood group distribution was
      as follows: O: 356 (49.%); A: 190 (26.%); B: 152 (21%); and AB: 28 (4%). A total
      of 28 (3.86%) pregnant women were RhD negative. Anti-D alloantibodies were
      detected in 88 (12.1%) of the participants; and of these, 13 (14.8%) were RhD
      negative. Statistically significant risk factors for anti-D alloimmunization
      included miscarriage, stillbirth, and postpartum hemorrhage. CONCLUSION: Blood
      group O was the most common among the pregnant women in this study and the
      prevalence of Rh negativity was 3.8%. The frequency of anti-D alloimmunization
      among pregnant women in Kasese District was 12.12%, with 85.5% of these being RhD
      positive. Risk factors such as a history of stillbirths, miscarriages, and
      incidence of postpartum hemorrhage were significantly associated with anti-D
      alloimmunization. There is a need to routinely carry out antenatal blood grouping
      and IAT screening on pregnant women in Uganda to detect anti-D alloimmunization.
      Given the high prevalence of anti-D alloantibody formation among RhD-positive
      women, we recommend additional research studies on the role of autoimmunity among
      antigen-positive women, as well as the occurrence of RhD variants plus their
      implications on hemolytic disease of the fetus and newborn, in Uganda.

PMID- 25945070
TI  - Consistency and sealing of advanced bipolar tissue sealers.
AB  - OBJECTIVES: The aim of this study was to evaluate two commonly used advanced
      bipolar devices (ENSEAL((r)) G2 Tissue Sealers and LigaSureTM Blunt Tip) for
      compression uniformity, vessel sealing strength, and consistency in bench-top
      analyses. METHODS: Compression analysis was performed with a foam pad/sensor
      apparatus inserted between closed jaws of the instruments. Average pressures
      (psi) were recorded across the entire inside surface of the jaws, and over the
      distal one-third of jaws. To test vessel sealing strength, ex vivo pig carotid
      arteries were sealed and transected and left and right (sealed) halves of vessels
      were subjected to burst pressure testing. The maximum bursting pressures of each
      half of vessels were averaged to obtain single data points for analysis. The
      absence or presence of tissue sticking to device jaws was noted for each
      transected vessel. RESULTS: Statistically higher average compression values were
      found for ENSEAL((r)) instruments (curved jaw and straight jaw) compared to
      LigaSureTM, P<0.05. Moreover, the ENSEAL((r)) devices retained full compression
      at the distal end of jaws. Significantly higher and more consistent median burst
      pressures were noted for ENSEAL((r)) devices relative to LigaSureTM through 52
      firings of each device (P<0.05). LigaSureTM showed a significant reduction in
      median burst pressure for the final three firings (cycles 50-52) versus the first
      three firings (cycles 1-3), P=0.027. Tissue sticking was noted for 1.39% and
      13.3% of vessels transected with ENSEAL((r)) and LigaSureTM, respectively.
      CONCLUSION: In bench-top testing, ENSEAL((r)) G2 sealers produced more uniform
      compression, stronger and more consistent vessel sealing, and reduced tissue
      sticking relative to LigaSureTM.

PMID- 25945072
TI  - Teaching safe prescribing to medical students: perspectives in the UK.
AB  - Prescribing is a characteristic role of a medical practitioner. On graduating
      from medical school, students are presumed to have acquired the necessary
      pharmacology knowledge underpinning the therapeutics and developed their personal
      skills and behaviors in order to write a safe and effective prescription (The
      Four Ps). However, there are reports of errors in medical prescribing and
      dissatisfied feedback from recent graduates, which evidence potential flaws in
      the current training in the practice of prescribing. We examine the Four Ps from
      a systems approach and offer scope for educators and curriculum designers to
      review and reflect on their current undergraduate teaching, learning, and
      assessment strategies in a similar manner. We also adopt a national framework of
      common competencies required of all prescribers to remain effective and safe in
      their area of practice as a more objective layer to the broader learning outcomes
      of the General Medical Council Tomorrow's Doctors 2009. This exercise
      demonstrates where standard, recognized competencies for safe prescribing can be
      accommodated pedagogically within existing medical curricula. 

PMID- 25945073
TI  - Does how much a resident teaches impact performance? A comparison of preclinical
      teaching hours to pathology residents' in-service examination scores.
AB  - BACKGROUND: While others have studied the effects of resident teaching on medical
      student performance, few have examined the benefits to the resident educator. Our
      study compared the quantity of pathology residents' didactic teaching with their
      performance on in-service examinations. METHODS: The academic records of
      anatomic/clinical pathology residents over 10 years were reviewed. Scores on step
      I of the United States Medical Licensing Examination (USMLE((r))), the annual
      percentile on the in-service examination, and preclinical teaching hours for each
      resident were obtained. RESULTS: Average annual teaching hours showed a weak
      positive correlation with mean in-service examination performance. Those below
      the 50th percentile had a lower number of teaching hours (average 7.8) than above
      the 50th percentile (mean 10.4, P=0.01). The incremental positive association
      between the two metrics increased by year in training and was strongest among
      senior residents, even controlling for USMLE performance (P<0.01). CONCLUSION:
      There is an association between the amount of pathology residents' preclinical
      educational activity and their mean performance on in-service examinations.

PMID- 25945074
TI  - British medical students suffer an inordinate amount of stress compared to other
      university students: fact or fiction?

PMID- 25945075
TI  - Myeloablative chemotherapy with autologous stem cell transplant for desmoplastic
      small round cell tumor.
AB  - Desmoplastic small round cell tumor (DSRCT), a rare, aggressive neoplasm, has a
      poor prognosis. In this prospective study, we evaluated the role of myeloablative
      chemotherapy, followed by autologous stem cell transplant in improving survival
      in DSRCT. After high-dose induction chemotherapy and surgery, 19 patients with
      chemoresponsive DSRCT underwent autologous stem cell transplant. Myeloablative
      chemotherapy consisted of carboplatin (400-700 mg/m(2)/day for 3 days) + thiotepa
      (300 mg/m(2)/day for 3 days) +/- topotecan (2 mg/m(2)/day for 5 days). All
      patients were engrafted and there was no treatment-related mortality. Seventeen
      patients received radiotherapy to sites of prior or residual disease at a median
      of 12 weeks after transplant. Five-year event-free and overall survival were 11
      +/- 7% and 16 +/- 8%, respectively. Two patients survive disease-free 16 and 19
      years after transplant (both in complete remission before transplant). 14
      patients had progression and died of disease at a median of 18 months following
      autologous transplant. These data do not justify the use of myeloablative
      chemotherapy with carboplatin plus thiotepa in patients with DSRCT. Alternative
      therapies should be considered for this aggressive neoplasm. 

PMID- 25945077
TI  - Being Immigrant in their Own Country: Experiences of Bosnians Immigrants in
      Contact with Health Care System in Bosnia and Herzegovina.
AB  - BACKGROUND: Bosnia and Herzegovina became an independent state (6(th) April 1992)
      after referendum for the independence of Bosnia and Herzegovina which was held on
      29 February and 1 March 1992. On the referendum voted total 2,073,568 voters
      (63.6% turnout) and 99.7% were in favor of independence, and 0.3% against.
      According to the provisions of the peace agreement, particularly in Annex IV of
      the Constitution of Bosnia and Herzegovina, the country continues to exist as an
      independent state. Like all others institutions, even the health-care system was
      separated between Federation and the other part of Bosnia and Herzegovina. The
      right to social and medical services in Bosnia and Herzegovina is realized
      entities level and regulated by entity laws on social and health-care. AIMS: The
      aim was to explore how immigrants born in Bosnia and Herzegovina and living as
      refugees in their own country experience different institutions in Bosnia and
      Herzegovina with the special focus on the health-care system. We also
      investigated the mental health of those immigrants. PATIENTS AND METHODS: Focus
      group interviews, with 21 respondents born in Bosnia and Herzegovina and living
      as refugees in their own country, were carried out. Content analysis was used for
      interpretation of the data. RESULTS: The analysis resulted in two categories: the
      health-care in pre-war period and the health-care system in post-war period. The
      health-care organization, insurance system, language differences, health-care
      professional's attitude and corruption in health-care system were experienced as
      negative by all respondents. None of the participants saw a way out of this
      difficult situation and saw no glimmer of light in the tunnel. None of the
      participants could see any bright future in the health-care system. CONCLUSION:
      Health-care system should be adjusted according to the needs of both the local
      population born as well as the immigrants. Health-care professionals must be
      aware of the difficulties of living as immigrants in one's own country. In order
      to provide health-care on a high level of quality, health-care professionals must
      meet all the expectations of the patients, and not to expect that patients should
      fulfil the expectations of the health-care professionals. Different educational
      activities, such as lectures, seminars and conferences, are needed with the
      purpose of the optimal use of the health-care system for people that have been
      forced to become refuges in their own country.

PMID- 25945076
TI  - Glucose 6-phosphate dehydrogenase knockdown enhances IL-8 expression in HepG2
      cells via oxidative stress and NF-kappaB signaling pathway.
AB  - BACKGROUND: This study was designed to investigate the effect of glucose 6
      phosphate dehydrogenase (G6PD) deficiency on pro-inflammatory cytokine secretion
      using a palmitate-induced inflammation HepG2 in vitro model. The modulation of
      cellular pro-inflammatory cytokine expression under G6PD deficiency during
      chronic hepatic inflammation has never been investigated before. METHODS: The
      culture medium of untreated and palmitate-treated G6PD-scramble (Sc) and G6PD
      knockdown (Gi) HepG2 cells were subjected to cytokine array analysis, followed by
      validation with ELISA and qRT-PCR of the target cytokine. The mechanism of
      altered cytokine secretion in palmitate-treated Sc and Gi HepG2 cells was
      examined in the presence of anti-oxidative enzyme (glutathione peroxidase, GPX),
      anti-inflammatory agent (curcumin), NF-kappaB inhibitor (BAY11-7085) and specific
      SiRNA against NF-kappaB subunit p65. RESULTS: Cytokine array analysis indicated
      that IL-8 is most significantly increased in G6PD-knockdown HepG2 cells. The up
      regulation of IL-8 caused by G6PD deficiency in HepG2 cells was confirmed in
      other G6PD-deficient cells by qRT-PCR. The partial reduction of G6PD deficiency
      derived IL-8 due to GPX and NF-kappaB blockers indicated that G6PD deficiency up
      regulates pro-inflammatory cytokine IL-8 through oxidative stress and NF-kappaB
      pathway. CONCLUSIONS: G6PD deficiency predisposes cells to enhanced production of
      pro-inflammatory cytokine IL-8. Mechanistically, G6PD deficiency up-regulates IL
      8 through oxidative stress and NF-kappaB pathway. The palmitate-induced
      inflammation in G6PD-deficient HepG2 cells could serve as an in vitro model to
      study the role of altered redox homeostasis in chronic hepatic inflammation.

PMID- 25945078
TI  - Predictors of nurses' intention and behavior in using health literacy strategies
      in patient education based on the theory of planned behavior.
AB  - BACKGROUND: Health literacy is one of the most important priorities for improving
      health care quality through enhancing patient-provider communication.
      Implementing health literacy strategies enable nurses to provide information and
      instructions for patients in a manner that is more commensurate and
      understandable. The purpose of this study was to investigate the factors
      affecting nurses' intention to implement health literacy strategies in patient
      education based on theory of planned behavior. METHODS: A cross-sectional study
      was done on 148 nurse practitioners of AL-Zahra educational hospital in Isfahan,
      Iran, using a descriptive-analytic method. Data collected via a standardized
      questionnaire based on theory of planned behavior constructed and analyzed by
      SPSS v.17 using ANOVA, Independent T-test, Pearson correlation and linear
      regression. RESULTS: There was statistically significant correlation between
      using health literacy strategies and marriage status, attending in retraining
      courses, employment type, job history, and job status. Perceived behavioral
      control was the most powerful predictor of intention (beta=0.417) and use health
      literacy strategies in patient education and behavior of nurses (beta=0.33).
      CONCLUSION: According to the findings of this study, perceived behavioral control
      is a powerful determinant of nurses' intention and behavior of using health
      literacy strategies in patient education. Hence we recommend nurse educators to
      pay special attention to the constructs of this theory mainly perceived
      behavioral control in retrain courses about patient education and health literacy
      strategies.

PMID- 25945079
TI  - The effect of acute vs chronic magnesium supplementation on exercise and recovery
      on resistance exercise, blood pressure and total peripheral resistance on
      normotensive adults.
AB  - BACKGROUND: Magnesium supplementation has previously shown reductions in blood
      pressure of up to 12 mmHg. A positive relationship between magnesium
      supplementation and performance gains in resistance exercise has also been seen.
      However, no previous studies have investigated loading strategies to optimise
      response. The aim of this study was to assess the effect of oral magnesium
      supplementation on resistance exercise and vascular response after intense
      exercise for an acute and chronic loading strategy on a 2-day repeat protocol.
      METHODS: The study was a randomised, double-blind, cross-over design, placebo
      controlled 2 day repeat measure protocol (n = 13). Intense exercise (40 km time
      trial) was followed by bench press at 80% 1RM to exhaustion, with blood pressure
      and total peripheral resistance (TPR) recorded. 300 mg/d elemental magnesium was
      supplemented for either a 1 (A) or 4 (Chr) week loading strategy. Food diaries
      were recorded. RESULTS: Dietary magnesium intake was above the Reference Nutrient
      Intake (RNI) for all groups. Bench press showed a significant increase of 17.7%
      (p = 0.031) for A on day 1. On day 2 A showed no decrease in performance whilst
      Chr showed a 32.1% decrease. On day 2 post-exercise systolic blood pressure (SBP)
      was significantly lower in both A (p = 0.0.47) and Chr (p = 0.016) groups.
      Diastolic blood pressure (DBP) showed significant decreases on day 2 solely for A
      (p = 0.047) with no changes in the Chr. TPR reduced for A on days 1 and 2 (p =
      0.031) with Chr showing an increase on day 1 (p = 0.008) and no change on day 2.
      CONCLUSION: There was no cumulative effect of Chr supplementation compared to A.
      A group showed improvement for bench press concurring with previous research
      which was not seen in Chr. On day 2 A showed a small non-significant increase but
      not a decrement as expected with Chr showing a decrease. DBP showed reductions in
      both Chr and A loading, agreeing with previous literature. This is suggestive of
      a different mechanism for BP reduction than for muscular strength. TPR showed
      greater reductions with A than Chr, which would not be expected as both
      interventions had reductions in BP, which is associated with TPR.

PMID- 25945081
TI  - Vilazodone for the treatment of major depressive disorder: an evidence-based
      review of its place in therapy.
AB  - INTRODUCTION: It has clearly been demonstrated that depressive disorders
      constitute a major worldwide public health problem, with massive economic and
      quality-of-life consequences. Existing pharmacological treatments have limited
      efficacy, with only about a third of patients achieving remission on any one
      medication. Delayed onset of action and variable tolerability contribute to this
      limited efficacy. Vilazodone, introduced in the US in 2011, has been described as
      the first member of the serotonin partial agonist-reuptake inhibitor (SPARI)
      class of medications, combining serotonin-reuptake inhibition with 5-HT1A partial
      agonism. This agent could potentially have benefits for subgroups of depressed
      patients, including depressed patients with comorbid anxiety and patients with
      anxiety disorders, and might have fewer sexual side effects than selective
      serotonin-reuptake inhibitors (SSRIs). AIMS: We reviewed existing clinical trials
      that assess the benefits of vilazodone for treatment of major depression.
      EVIDENCE REVIEW: In clinical trials, including two Phase III studies and two
      Phase IV studies, vilazodone has been shown to have efficacy greater than placebo
      on the Montgomery-Asberg Depression Rating Scale, comparable efficacy to
      citalopram, and continued benefit after 52 weeks of treatment. The safety profile
      for vilazodone is comparable to other SSRI medications, and tolerability also
      appears generally comparable to other SSRI medications. PLACE IN THERAPY:
      Vilazodone, which has been described as the first-of-class SPARI medication, may
      potentially have benefits for subgroups of patients, particularly those depressed
      individuals with coexisting anxiety symptoms or anxiety disorders. However,
      convincing evidence for these benefits has as yet not been published.

PMID- 25945083
TI  - Harmony search method: theory and applications.
AB  - The Harmony Search (HS) method is an emerging metaheuristic optimization
      algorithm, which has been employed to cope with numerous challenging tasks during
      the past decade. In this paper, the essential theory and applications of the HS
      algorithm are first described and reviewed. Several typical variants of the
      original HS are next briefly explained. As an example of case study, a modified
      HS method inspired by the idea of Pareto-dominance-based ranking is also
      presented. It is further applied to handle a practical wind generator optimal
      design problem. 

PMID- 25945080
TI  - Integrative and systemic approaches for evaluating PPARbeta/delta (PPARD)
      function.
AB  - The peroxisome proliferator-activated receptors (PPARs) are a group of nuclear
      receptors that function as transcription factors regulating the expression of
      genes involved in cellular differentiation, development, metabolism and also
      tumorigenesis. Three PPAR isotypes (alpha, beta/delta and gamma) have been
      identified, among which PPARbeta/delta is the most difficult to functionally
      examine due to its tissue-specific diversity in cell fate determination, energy
      metabolism and housekeeping activities. PPARbeta/delta acts both in a ligand
      dependent and -independent manner. The specific type of regulation, activation or
      repression, is determined by many factors, among which the type of ligand, the
      presence/absence of PPARbeta/delta-interacting corepressor or coactivator
      complexes and PPARbeta/delta protein post-translational modifications play major
      roles. Recently, new global approaches to the study of nuclear receptors have
      made it possible to evaluate their molecular activity in a more systemic fashion,
      rather than deeply digging into a single pathway/function. This systemic approach
      is ideally suited for studying PPARbeta/delta, due to its ubiquitous expression
      in various organs and its overlapping and tissue-specific transcriptomic
      signatures. The aim of the present review is to present in detail the diversity
      of PPARbeta/delta function, focusing on the different information gained at the
      systemic level, and describing the global and unbiased approaches that combine a
      systems view with molecular understanding. 

PMID- 25945084
TI  - Role of gut barrier function in the pathogenesis of nonalcoholic Fatty liver
      disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is one of the most common forms of
      chronic liver disease, and its incidence is increasing year by year. Many efforts
      have been made to investigate the pathogenesis of this disease. Since 1998 when
      Marshall proposed the conception of "gut-liver axis," more and more researchers
      have paid close attention to the role of gut barrier function in the pathogenesis
      of NAFLD. The four aspects of gut barrier function, including physical, chemical,
      biological, and immunological barriers, are interrelated closely and related to
      NAFLD. In this paper, we present a summary of research findings on the
      relationship between gut barrier dysfunction and the development of NAFLD, aiming
      at illustrating the role of gut barrier function in the pathogenesis of this
      disease. 

PMID- 25945085
TI  - Risk factors for migration, fracture, and dislocation of pancreatic stents.
AB  - Aim. To analyze the risk factors for pancreatic stent migration, dislocation, and
      fracture in chronic pancreatitis patients with pancreatic strictures. Materials
      and Methods. Endoscopic stent placements (total 386 times) were performed in 99
      chronic pancreatitis patients with pancreatic duct stenosis at our institution
      between April 2006 and June 2014. We retrospectively examined the frequency of
      stent migration, dislocation, and fracture and analyzed the patient factors and
      stent factors. We also investigated the retrieval methods for migrated and
      fractured stents and their success rates. Results. The frequencies of stent
      migration, dislocation, and fracture were 1.5% (5/396), 0.8% (3/396), and 1.2%
      (4/396), respectively. No significant differences in the rates of migration,
      dislocation, or fracture were noted on the patient factors (etiology, cases
      undergoing endoscopic pancreatic sphincterotomy, location of pancreatic duct
      stenosis, existence of pancreatic stone, and approach from the main or minor
      papilla) and stent factors (duration of stent placement, numbers of stent
      placements, stent shape, diameter, and length). Stent retrieval was successful in
      all cases of migration. In cases of fractured stents, retrieval was successful in
      2 of 4 cases. Conclusion. Stent migration, fracture, and dislocation are
      relatively rare, but possible complications. A good understanding of retrieval
      techniques is necessary. 

PMID- 25945082
TI  - Comparative proteomic analysis of hypertrophic chondrocytes in osteoarthritis.
AB  - BACKGROUND: Osteoarthritis (OA) is a multi-factorial disease leading
      progressively to loss of articular cartilage and subsequently to loss of joint
      function. While hypertrophy of chondrocytes is a physiological process implicated
      in the longitudinal growth of long bones, hypertrophy-like alterations in
      chondrocytes play a major role in OA. We performed a quantitative proteomic
      analysis in osteoarthritic and normal chondrocytes followed by functional
      analyses to investigate proteome changes and molecular pathways involved in OA
      pathogenesis. METHODS: Chondrocytes were isolated from articular cartilage of ten
      patients with primary OA undergoing knee replacement surgery and six normal
      donors undergoing fracture repair surgery without history of joint disease and no
      OA clinical manifestations. We analyzed the proteome of chondrocytes using high
      resolution mass spectrometry and quantified it by label-free quantification and
      western blot analysis. We also used WebGestalt, a web-based enrichment tool for
      the functional annotation and pathway analysis of the differentially synthesized
      proteins, using the Wikipathways database. ClueGO, a Cytoscape plug-in, is also
      used to compare groups of proteins and to visualize the functionally organized
      Gene Ontology (GO) terms and pathways in the form of dynamical network
      structures. RESULTS: The proteomic analysis led to the identification of a total
      of ~2400 proteins. 269 of them showed differential synthesis levels between the
      two groups. Using functional annotation, we found that proteins belonging to
      pathways associated with regulation of the actin cytoskeleton, EGF/EGFR, TGF
      beta, MAPK signaling, integrin-mediated cell adhesion, and lipid metabolism were
      significantly enriched in the OA samples (p <=10(-5)). We also observed that the
      proteins GSTP1, PLS3, MYOF, HSD17B12, PRDX2, APCS, PLA2G2A SERPINH1/HSP47 and
      MVP, show distinct synthesis levels, characteristic for OA or control
      chondrocytes. CONCLUSION: In this study we compared the quantitative changes in
      proteins synthesized in osteoarthritic compared to normal chondrocytes. We
      identified several pathways and proteins to be associated with OA chondrocytes.
      This study provides evidence for further testing on the molecular mechanism of
      the disease and also propose proteins as candidate markers of OA chondrocyte
      phenotype.

PMID- 25945086
TI  - Serrated polyps and their alternative pathway to the colorectal cancer: a
      systematic review.
AB  - Colorectal cancer (CRC) is the third most frequently diagnosed cancer in the
      world. For a long time, only one pathway of colorectal carcinogenesis was known.
      In recent years, a new "alternative" pathway through serrated adenoma was
      described. Recent meta-analysis estimated these cancers as about 10% to 30% of
      all CRCs. Serrated polyps are the second most popular groups of polyps (after
      conventional adenomas) found during colonoscopy. Serrated polyps of the colon are
      clinically and molecularly diverse changes that have common feature as crypt
      luminal morphology characterized by glandular serration. Evidence suggests that
      subtypes of serrated polyps, particularly TSA and SSA/P, can lead to
      adenocarcinoma through the serrated pathway. Moreover, the data indicate that the
      SSA/P are the precursors of colorectal carcinoma by MSI and may be subject to
      rapid progression to malignancy. An important step to reduce the incidence of CRC
      initiated by the serrated pathway is to improve the detection of serrated polyps
      and to ensure their complete removal during endoscopy. Understanding of the so
      called serrated carcinogenesis pathway is an important step forward in expanding
      possibilities in the prevention of CRC. 

PMID- 25945087
TI  - Hybrid push-pull endoscopic and laparoscopic full thickness resection for the
      minimally invasive management of gastrointestinal stromal tumors: a pilot
      clinical study.
AB  - Background. Gastric gastrointestinal stromal tumors (GISTs) that are
      predominantly endophytic or in anatomically complex locations pose a challenge
      for laparoscopic wedge resection; however, endoscopic resection can be associated
      with a positive deep margin given the fourth-layer origin of the tumors. Methods.
      Patients at two tertiary care academic medical centers with gastric GISTs in
      difficult anatomic locations or with a predominant endophytic component were
      considered for enrollment. Preoperative esophagogastroduodenoscopy (EGD),
      endoscopic ultrasound (EUS) with or without fine needle aspiration (FNA), and
      cross-sectional imaging were performed. Eligible patients were offered and
      consented for hybrid and standard management. Results. Over ten months, four
      patients in two institutions with anatomically complex or endophytic GISTs
      underwent successful, uncomplicated push-pull hybrid procedures. GIST was
      confirmed in all resection specimens. Conclusion. In a highly selected
      population, the hybrid push-pull approach was safe and effective in the removal
      of complex gastric GISTs. Endoscopic resection alone was associated with a
      positive deep margin, which the push-pull technique manages with a laparoscopic,
      full thickness, R0 resection. This novel, minimally invasive, hybrid laparoscopic
      and endoscopic push-pull technique is a safe and feasible alternative in the
      management of select GISTs that are not amenable to standard laparoscopic
      resection. 

PMID- 25945088
TI  - Fast MR Imaging of the Paediatric Abdomen with CAIPIRINHA-Accelerated T1w 3D
      FLASH and with High-Resolution T2w HASTE: A Study on Image Quality.
AB  - The aim of this study was to explore the applicability of fast MR techniques to
      routine paediatric abdominopelvic MRI at 1.5 Tesla. "Controlled Aliasing in
      Parallel Imaging Results in Higher Acceleration-" (CAIPIRINHA-) accelerated
      contrast-enhanced-T1w 3D FLASH imaging was compared to standard T1w 2D FLASH
      imaging with breath-holding in 40 paediatric patients and to respiratory
      triggered T1w TSE imaging in 10 sedated young children. In 20 nonsedated
      patients, we compared T2w TIRM to fat-saturated T2w HASTE imaging. Two observers
      performed an independent and blinded assessment of overall image quality.
      Acquisition time was reduced by the factor of 15 with CAIPIRINHA-accelerated T1w
      FLASH and by 7 with T2w HASTE. With CAIPIRINHA and with HASTE, there were
      significantly less motion artefacts in nonsedated patients. In sedated patients,
      respiratory-triggered T1w imaging in general showed better image quality.
      However, satisfactory image quality was achieved with CAIPIRINHA in two sedated
      patients where respiratory triggering failed. In summary, fast scanning with
      CAIPIRINHA and HASTE presents a reliable high quality alternative to standard
      sequences in paediatric abdominal MRI. Paediatric patients, in particular,
      benefit greatly from fast image acquisition with less breath-hold cycles or
      shorter sedation. 

PMID- 25945089
TI  - Nuclear Factor Kappa B, Matrix Metalloproteinase-1, p53, and Ki-67 Expressions in
      the Primary Tumors and the Lymph Node Metastases of Colorectal Cancer Cases.
AB  - Colorectal cancer (CRC) is the third most frequent malignancy. Many factors such
      as NF-kappaB, matrix metalloproteinase-1 (MMP-1), p53, and Ki-67 are likely to be
      involved in its development and progression. Lymph node metastases indicate
      increased tumor burden and tumor cell heterogeneity and affect both the treatment
      strategies and the prognosis. In this study, expressions of NF-kappaB, MMP-1,
      p53, and Ki-67 were between the primary tumors and lymph node metastases in 110
      Dukes' stage C, CRC cases by immunohistochemical methods, related to patients'
      clinical outcomes. NF-kappaB, p53, and Ki-67 expressions were significantly
      higher in the metastatic lymph nodes compared to the primary tumor tissues (P =
      0.04, P = 0.04, and P = 0.01, resp.). In the metastatic lymph nodes NF-kappaB
      expression was correlated with both p53 (r = 0.546, P = 0.003) and Ki-67 (r =
      0.586, P = 0.0001) expressions. The univariant and multivariant analyses showed
      that only "pT stage" preserved an independent prognostic significance for
      recurrence-free survival rates and 5-year overall survival rates (P < 0.001 for
      both). Metastatic cells can acquire different biological characteristics compared
      to their primaries. Elucidation of properties acquired by metastatic cells is
      important in order to better determine prognosis, reverse drug resistance, and
      discover new treatment alternatives. 

PMID- 25945090
TI  - Androgen Receptors Expression in Pituitary of Male Viscacha in relation to Growth
      and Reproductive Cycle.
AB  - The aim of this work was to study the androgen receptors (AR) expression in
      pituitary pars distalis (PD) of male viscachas in relation to growth and
      reproductive cycle. AR were detected by immunocytochemistry and quantified by
      image analysis. Pituitary glands from fetus, immature, prepubertal, and adult
      viscachas during their reproductive cycle were used. In the fetal PD, the
      immunoreactivity (ir) was mainly cytoplasmic. In immature and prepubertal
      animals, AR-ir was cytoplasmic (ARc-ir) and nuclear (ARn-ir) in medial region. In
      adult animals, ARn-ir cells were numerous at caudal end. AR regionalization
      varied between the PD zones in relation to growth. In immature animals, the ARn
      ir increased whereas the cytoplasmic expression decreased in relation to the
      fetal glands. The percentage of ARc-ir cells increased in prepubertal animals
      whereas the nuclear AR expression was predominant in adult viscachas. The AR
      expression changed in adults, showing minimum percentage in the gonadal
      regression period. The variation of nuclear AR expression was directly related
      with testosterone concentration. These results demonstrated variations in the
      immunostaining pattern, regionalization, and number of AR-ir cells throughout
      development, growth, and reproductive cycle, suggesting the involvement of AR in
      the regulation of the pituitary activity of male viscacha. 

PMID- 25945091
TI  - The janus face of stress on reproduction: from health to disease.
AB  - Parenthood is a fundamental feature of all known life. However, infertility has
      been recognized as a public health issue worldwide. But even when the offspring
      are conceived, in utero problems can lead to immediate (abortion), early (birth),
      and late (adulthood) consequences. One of the most studied factors is stress.
      However, stress response is, per se, of adaptive nature allowing the organism to
      cope with challenges. Stressors lead to deterioration if one is faced with too
      long lasting, too many, and seemingly unsolvable situations. In stress adaptation
      the hypothalamus-pituitary-adrenocortical axis and the resulting glucocorticoid
      elevation are one of the most important mechanisms. At cellular level stress can
      be defined as an unbalance between production of free radicals and antioxidant
      defenses. Oxidative stress is widely accepted as an important pathogenic
      mechanism in different diseases including infertility. On the other hand, the
      goal of free radical production is to protect the cells from infectious entities.
      This review aims to summarize the negative and positive influence of stress on
      reproduction as a process leading to healthy progeny. Special emphasis was given
      to the balance at the level of the organism and cells. 

PMID- 25945092
TI  - Contribution to More Patient-Friendly ART Treatment: Efficacy of Continuous Low
      Dose GnRH Agonist as the Only Luteal Support-Results of a Prospective,
      Randomized, Comparative Study.
AB  - Background. The aim of this pilot study was to evaluate intranasal buserelin for
      luteal phase support and compare its efficacy with standard vaginal progesterone
      in IVF/ICSI antagonist cycles. Methods. This is a prospective, randomized, open,
      parallel group study. Forty patients underwent ovarian hyperstimulation with
      human menopausal gonadotropin under pituitary inhibition with gonadotropin
      releasing hormone antagonist, while ovulation trigger and luteal support were
      achieved using intranasal GnRH agonist (group A). Twenty patients had their cycle
      downregulated with buserelin and stimulated with hMG, while ovulation trigger was
      achieved using 10,000 IU human chorionic gonadotropin with luteal support by
      intravaginal progesterone (group B). Results. No difference was observed in
      estradiol levels. Progesterone levels on day 5 were significantly lower in group
      A. However, significantly higher levels of luteinizing hormone were observed in
      group A during the entire luteal phase. Pregnancy rates (31.4% versus 22.2%),
      implantation rates (22% versus 15.4%), and clinical pregnancy rates (25.7% versus
      16.7%) were not statistically different between groups, although a trend towards
      higher rates was observed in group A. No luteal phase lasting less than 10 days
      was recorded in either group. Conclusion. Intranasal administration of buserelin
      is effective for providing luteal phase support in IVF/ICSI antagonist protocols.

PMID- 25945093
TI  - Index of orthodontic treatment need in obese adolescents.
AB  - Aim. This case-control retrospective study is aimed at assessing if obese
      adolescents need more orthodontic treatment in comparison with normal-weight
      patients of the same age. Methods. The test group included 100 obese subjects (50
      males and 50 females; average age: 13.09 +/- 1.19 years old) and the control
      group included 100 normal-weight patients matched for age and sex (50 males and
      50 females; average age: 13.07 +/- 1.26 years old). Clinical examinations were
      conducted on dental casts to assess the need of orthodontic treatment, by using
      the Index of Orthodontic Treatment Need (IOTN) (DHC, dental health component; AC,
      aesthetic components). Results. No statistically significant difference (P >
      0.05) was observed between the two groups with regard to AC. Obese females showed
      a significant (P < 0.05) higher percentage of DHC 3 (32%) in comparison to the
      normal-weight girls (22%); for the other grades of DHC and for the single kind of
      malocclusion, no significant difference was found. Conclusions. Obese adolescents
      showed a similar need for orthodontic treatment compared to normal-weight
      patients of the same age. However, in obese females, a slightly greater need for
      orthodontic treatment was observed, compared to normal-weight patients. 

PMID- 25945094
TI  - A new sensitive sensor for simultaneous differential pulse voltammetric
      determination of codeine and acetaminophen using a hydroquinone derivative and
      multiwall carbon nanotubes carbon paste electrode.
AB  - A new sensitive sensor was fabricated for simultaneous determination of codeine
      and acetaminophen based on 4-hydroxy-2-(triphenylphosphonio)phenolate (HTP) and
      multiwall carbon nanotubes paste electrode at trace levels. The sensitivity of
      codeine determination was deeply affected by spiking multiwall carbon nanotubes
      and a modifier in carbon paste. Electron transfer coefficient, alpha, catalytic
      electron rate constant, k, and the exchange current density, j 0, for oxidation
      of codeine at the HTP-MWCNT-CPE were calculated using cyclic voltammetry. The
      calibration curve was linear over the range 0.2-844.7 MUM with two linear
      segments, and the detection limit of 0.063 MUM of codeine was obtained using
      differential pulse voltammetry. The modified electrode was separated codeine and
      acetaminophen signals by differential pulse voltammetry. The modified electrode
      was applied for the determination of codeine and acetaminophen in biological and
      pharmaceutical samples with satisfactory results. 

PMID- 25945095
TI  - The challenging diagnosis of pancreatic masses: not all tumors are cancers.
AB  - In the elderly patients, where biopsy-induced complications could outweigh the
      benefit, the identification of pancreatic masses is generally referred to as a
      synonymous of pancreatic cancer and patients are dismissed with no further
      options than palliative and supportive care. Notwithstanding, not all pancreatic
      tumors are cancers and therefore alternative diagnoses need to be investigated,
      especially when patients are unfit for invasive diagnostic procedures. Here, we
      report a case of an aged patient that was admitted to an internal medicine
      division for a previously diagnosed pancreatic cancer. The reassessment of the
      diagnosis has allowed identifying the pancreatic mass as a manifestation of focal
      pancreatitis in the context of an IgG4-related disease. Accordingly, patient was
      treated with steroids with rapid clinical improvement. This clinical case
      suggests that autoimmune diseases should always be considered in the differential
      diagnosis of pancreatic masses of the elderly. 

PMID- 25945096
TI  - Successful isolation of viable adipose-derived stem cells from human adipose
      tissue subject to long-term cryopreservation: positive implications for adult
      stem cell-based therapeutics in patients of advanced age.
AB  - We examined cell isolation, viability, and growth in adipose-derived stem cells
      harvested from whole adipose tissue subject to different cryopreservation lengths
      (2-1159 days) from patients of varying ages (26-62 years). Subcutaneous abdominal
      adipose tissue was excised during abdominoplasties and was cryopreserved. The
      viability and number of adipose-derived stem cells isolated were measured after
      initial isolation and after 9, 18, and 28 days of growth. Data were analyzed with
      respect to cryopreservation duration and patient age. Significantly more viable
      cells were initially isolated from tissue cryopreserved <1 year than from tissue
      cryopreserved >2 years, irrespective of patient age. However, this difference did
      not persist with continued growth and there were no significant differences in
      cell viability or growth at subsequent time points with respect to
      cryopreservation duration or patient age. Mesenchymal stem cell markers were
      maintained in all cohorts tested throughout the duration of the study.
      Consequently, longer cryopreservation negatively impacts initial live adipose
      derived stem cell isolation; however, this effect is neutralized with continued
      cell growth. Patient age does not significantly impact stem cell isolation,
      viability, or growth. Cryopreservation of adipose tissue is an effective long
      term banking method for isolation of adipose-derived stem cells in patients of
      varying ages. 

PMID- 25945097
TI  - Differences in the gene expression profiles of slow- and fast-forming preinduced
      pluripotent stem cell colonies.
AB  - Induced pluripotent stem cells (iPSCs) are generated through a gradual process in
      which somatic cells undergo a number of stochastic events. In this study, we
      examined whether two different doxycycline-inducible iPSCs, slow-forming 4F2A
      iPSCs and fast-forming NGFP-iPSCs, have equivalent levels of pluripotency.
      Multiplex reverse-transcriptase PCR generated gene expression profiles (GEPs) of
      13 pluripotency genes in single initially formed-iPSC (if-iPSC) colonies of NGFP
      and 4F2A group. Assessment of GEP difference using a weighted root mean square
      deviation (wRMSD) indicates that 4F2A if-iPSCs are more closely related to mESCs
      than NGFP if-iPSCs. Consistently, Nanog and Sox2 genes were more frequently
      derepressed in 4F2A if-iPSC group. We further examined 20 genes that are
      implicated in reprogramming. They were, overall, more highly expressed in NGFP if
      iPSCs, differing from the pluripotency genes being more expressed in 4F2A if
      iPSCs. wRMSD analysis for these reprogramming-related genes confirmed that the
      4F2A if-iPSC colonies were less deviated from mESCs than the NGFP if-iPSC
      colonies. Our findings suggest that more important in attaining a better
      reprogramming is the mode of action by the given reprogramming factors, rather
      than the total activity of them exerting to the cells, as the thin-but-long
      lasting mode of action in 4F2A if-iPSCs is shown to be more effective than its
      full-but-short-lasting mode in NGFP if-iPSCs. 

PMID- 25945099
TI  - Dual Function of Wnt Signaling during Neuronal Differentiation of Mouse Embryonic
      Stem Cells.
AB  - Activation of Wnt signaling enhances self-renewal of mouse embryonic and neural
      stem/progenitor cells. In contrast, undifferentiated ES cells show a very low
      level of endogenous Wnt signaling, and ectopic activation of Wnt signaling has
      been shown to block neuronal differentiation. Therefore, it remains unclear
      whether or not endogenous Wnt/beta-catenin signaling is necessary for self
      renewal or neuronal differentiation of ES cells. To investigate this, we examined
      the expression profiles of Wnt signaling components. Expression levels of Wnts
      known to induce beta-catenin were very low in undifferentiated ES cells. Stable
      ES cell lines which can monitor endogenous activity of Wnt/beta-catenin signaling
      suggest that Wnt signaling was very low in undifferentiated ES cells, whereas it
      increased during embryonic body formation or neuronal differentiation.
      Interestingly, application of small molecules which can positively (BIO, GSK3beta
      inhibitor) or negatively (IWR-1-endo, Axin stabilizer) control Wnt/beta-catenin
      signaling suggests that activation of that signaling at different time periods
      had differential effects on neuronal differentiation of 46C ES cells. Further,
      ChIP analysis suggested that beta-catenin/TCF1 complex directly regulated the
      expression of Sox1 during neuronal differentiation. Overall, our data suggest
      that Wnt/beta-catenin signaling plays differential roles at different time points
      of neuronal differentiation. 

PMID- 25945098
TI  - Cell Cycle-Driven Heterogeneity: On the Road to Demystifying the Transitions
      between "Poised" and "Restricted" Pluripotent Cell States.
AB  - Cellular heterogeneity is now considered an inherent property of most stem cell
      types, including pluripotent stem cells, somatic stem cells, and cancer stem
      cells, and this heterogeneity can exist at the epigenetic, transcriptional, and
      posttranscriptional levels. Several studies have indicated that the stochastic
      activation of signaling networks may promote heterogeneity and further that this
      heterogeneity may be reduced by their inhibition. But why different cells in the
      same culture respond in a nonuniform manner to the identical exogenous signals
      has remained unclear. Recent studies now demonstrate that the cell cycle position
      directly influences lineage specification and specifically that pluripotent stem
      cells initiate their differentiation from the G1 phase. These studies suggest
      that cells in G1 are uniquely "poised" to undergo cell specification. G1 cells
      are therefore more prone to respond to differentiation cues, which may explain
      the heterogeneity of developmental factors, such as Gata6, and pluripotency
      factors, such as Nanog, in stem cell cultures. Overall, this raises the
      possibility that G1 serves as a "Differentiation Induction Point." In this
      review, we will reexamine the literature describing heterogeneity of pluripotent
      stem cells, while highlighting the role of the cell cycle as a major determinant.

PMID- 25945100
TI  - Concise Review: Are Stimulated Somatic Cells Truly Reprogrammed into an ES/iPS
      Like Pluripotent State? Better Understanding by Ischemia-Induced Multipotent Stem
      Cells in a Mouse Model of Cerebral Infarction.
AB  - Following the discovery of pluripotent stem (PS) cells such as embryonic stem
      (ES) and induced pluripotent stem (iPS) cells, there has been a great hope that
      injured tissues can be repaired by transplantation of ES/iPS-derived various
      specific types of cells such as neural stem cells (NSCs). Although PS cells can
      be induced by ectopic expression of Yamanaka's factors, it is known that several
      stimuli such as ischemia/hypoxia can increase the stemness of somatic cells via
      reprogramming. This suggests that endogenous somatic cells acquire stemness
      during natural regenerative processes following injury. In this study, we
      describe whether somatic cells are converted into pluripotent stem cells by
      pathological stimuli without ectopic expression of reprogramming factors based on
      the findings of ischemia-induced multipotent stem cells in a mouse model of
      cerebral infarction. 

PMID- 25945101
TI  - The Allergic Rhinitis - Clinical Investigator Collaborative (AR-CIC): nasal
      allergen challenge protocol optimization for studying AR pathophysiology and
      evaluating novel therapies.
AB  - BACKGROUND: The Nasal Allergen Challenge (NAC) model allows the study of Allergic
      Rhinitis (AR) pathophysiology and the proof of concept of novel therapies. The
      Allergic Rhinitis - Clinical Investigator Collaborative (AR-CIC) aims to optimize
      the protocol, ensuring reliability and repeatability of symptoms to better
      evaluate the therapies under investigation. METHODS: 20 AR participants were
      challenged, with 4-fold increments of their respective allergens every 15
      minutes, to determine the qualifying allergen concentration (QAC) at which the
      Total Nasal Symptom Score (TNSS) of >=10/12 OR a Peak Nasal Inspiratory Flow
      (PNIF) reduction of >=50% from baseline was achieved. At the NAC visit, the QAC
      was used in a single challenge and TNSS and PNIF were recorded at baseline, 15
      minutes, 30 minutes, 1 hour, and hourly up to 12 hours. 10 additional ragweed
      allergic participants were qualified at TNSS of >=8/12 AND >=50% PNIF reduction;
      the Cumulative Allergen Challenge (CAC) of all incremental doses was used during
      the NAC visit. 4 non-allergic participants were challenged with the highest
      allergen concentration. RESULTS: In the QAC study, a group qualified by only
      meeting PNIF criteria achieved lower TNSS than those achieving either TNSS
      criteria or PNIIF+TNSS (p<0.01). During the NAC visit, participants in both
      studies reached their peak symptoms at 15minutes followed by a gradual decline,
      significantly different from non-allergic participants. The "PNIF only" group
      experienced significantly lower TNSS than the other groups during NAC visit. QAC
      and CAC participants did not reach the same peak TNSS during NAC that was
      achieved at screening. QAC participants qualifying based on TNSS or TNSS+PNIF
      managed to maintain PNIF scores. CONCLUSIONS: Participants experienced reliable
      symptoms of AR in both studies, using both TNSS and PNIF reduction as part of the
      qualifying criteria proved better for qualifying participants at screening.
      Phenotyping based on pattern of symptoms experienced is possible and allows the
      study of AR pathophysiology and can be applied in evaluation of efficacy of a
      novel medication. The AR-CIC aims to continue to improve the model and employ it
      in phase 2 and 3 clinical trials.

PMID- 25945102
TI  - Triptolide-Mediated Apoptosis by Suppression of Focal Adhesion Kinase through
      Extrinsic and Intrinsic Pathways in Human Melanoma Cells.
AB  - Triptolide (TPL) has been shown to inhibit cell proliferation and induce
      apoptosis in various human cancer cells; however, the precise mechanism of
      apoptosis induced by TPL in human melanoma cells has not yet been elucidated. In
      this study, we investigated the precise mechanism underlying cytocidal effects of
      TPL on human melanoma cells. Treatment of human melanoma cells with TPL
      significantly inhibited cell growth and induced apoptosis, as evidenced by flow
      cytometry and annexin V-fluorescein isothiocyanate analyses. TPL increased the
      levels of Fas and Fas-associated death domain (FADD) and induced cleavage of Bid
      by activation of caspase-8 and cytochrome c release from mitochondria to the
      cytosol, which resulted in activation of caspase-9 and caspase-3. Moreover, TPL
      induced apoptosis in SK-MEL-2 cells was mediated through dephosphorylation of
      focal adhesion kinase (FAK) and its cleavage by caspase-8-mediated caspase-3
      activation via upregulation of Fas expression. We also found that TPL mediated
      the dissociation of receptor-interacting protein (RIP) from FAK and enhanced the
      formation of RIP/Fas complex formation initiating cell death. In conclusion, our
      data firstly demonstrated that TPL induces apoptosis by both extrinsic and
      intrinsic apoptosis pathways in human melanoma cells and identified that RIP
      shuttles between Fas and FAK to mediate apoptosis. 

PMID- 25945103
TI  - Effect of Oenothera odorata Root Extract on Microgravity and Disuse-Induced
      Muscle Atrophy.
AB  - Muscle atrophy, a reduction of muscle mass, strength, and volume, results from
      reduced muscle use and plays a key role in various muscular diseases. In the
      microgravity environment of space especially, muscle atrophy is induced by muscle
      inactivity. Exposure to microgravity induces muscle atrophy through several
      biological effects, including associations with reactive oxygen species (ROS).
      This study used 3D-clinostat to investigate muscle atrophy caused by oxidative
      stress in vitro, and sciatic denervation was used to investigate muscle atrophy
      in vivo. We assessed the effect of Oenothera odorata root extract (EVP) on muscle
      atrophy. EVP helped recover cell viability in C2C12 myoblasts exposed to
      microgravity for 24 h and delayed muscle atrophy in sciatic denervated mice.
      However, the expressions of HSP70, SOD1, and ceramide in microgravity-exposed
      C2C12 myoblasts and in sciatic denervated mice were either decreased or
      completely inhibited. These results suggested that EVP can be expected to have a
      positive effect on muscle atrophy by disuse and microgravity. In addition, EVP
      helped characterize the antioxidant function in muscle atrophy. 

PMID- 25945104
TI  - Pharmacological and Genotoxic Properties of Polyphenolic Extracts of Cedrela
      odorata L. and Juglans regia L. Barks in Rodents.
AB  - Evaluation of the phenolic compounds and antioxidant activity of Cedrela odorata
      L. and Juglans regia L. bark extracts was performed in vitro. Juglans regia
      showed greater extract concentration and higher antioxidant activity.
      Hypoglycemic activity in rats was assessed by generating a glucose tolerance
      curve and determining the area under the curve (AUC). Diabetes was later induced
      by an injection with streptozotocin (65 mg/kg of b.w.) and confirmed after 24
      hours. The extract was administered (200 mg/kg b.w.) over 10 days, and blood
      glucose was monitored and compared with a control group. The glucose AUC showed a
      hypoglycemic effect of J. regia and C. odorata in normal rats. Both extracts
      reduced hepatic lipid peroxidation in diabetic rats. Polyphenolic extracts
      reduced cholesterol levels in a hypercholesterolemic mouse model and decreased
      hepatic lipid peroxidation. Polyphenolic extract doses of 100 and 200 mg/kg b.w.
      were administered alone or with cyclophosphamide (CPA) 50 mg/kg ip, which was
      used as a positive control. Analyses were performed using leukocytes in a comet
      assay after 4 and 24 h of treatment. Genotoxic effects were evaluated by the
      comet assay, which showed that while J. regia extract had no effect, C. odorata
      extract induced slight damage at 200 mg/kg, with the formation of type 0 and 1
      comets. 

PMID- 25945105
TI  - Ginseng Purified Dry Extract, BST204, Improved Cancer Chemotherapy-Related
      Fatigue and Toxicity in Mice.
AB  - Cancer related fatigue (CRF) is one of the most common side effects of cancer and
      its treatments. A large proportion of cancer patients experience cancer-related
      physical and central fatigue so new strategies are needed for treatment and
      improved survival of these patients. BST204 was prepared by incubating crude
      ginseng extract with ginsenoside-beta-glucosidase. The purpose of the present
      study was to examine the effects of BST204, mixture of ginsenosides on 5
      fluorouracil (5-FU)-induced CRF, the glycogen synthesis, and biochemical
      parameters in mice. The mice were randomly divided into the following groups: the
      naive normal (normal), the HT-29 cell inoculated (xenograft), xenograft and 5-FU
      treated (control), xenograft + 5-FU + BST204-treated (100 and 200 mg/kg)
      (BST204), and xenograft + 5-FU + modafinil (13 mg/kg) treated group (modafinil).
      Running wheel activity and forced swimming test were used for evaluation of CRF.
      Muscle glycogen, serum inflammatory cytokines, aspartic aminotransferase (AST),
      alanine aminotransferase (ALT), creatinine (CRE), white blood cell (WBC),
      neutrophil (NEUT), red blood cell (RBC), and hemoglobin (HGB) were measured.
      Treatment with BST204 significantly increased the running wheel activity and
      forced swimming time compared to the control group. Consistent with the
      behavioral data, BST204 markedly increased muscle glycogen activity and
      concentrations of WBC, NEUT, RBC, and HGB. Also, tumor necrosis factor-alpha (TNF
      alpha) and interleukin-6 (IL-6), AST, ALT, and CRE levels in the serum were
      significantly reduced in the BST204-treated group compared to the control group.
      This result suggests that BST204 may improve chemotherapy-related fatigue and
      adverse toxic side effects. 

PMID- 25945106
TI  - Aqueous Date Flesh or Pits Extract Attenuates Liver Fibrosis via Suppression of
      Hepatic Stellate Cell Activation and Reduction of Inflammatory Cytokines,
      Transforming Growth Factor- beta 1 and Angiogenic Markers in Carbon Tetrachloride
      Intoxicated Rats.
AB  - Previous data indicated the protective effect of date fruit extract on oxidative
      damage in rat liver. However, the hepatoprotective effects via other mechanisms
      have not been investigated. This study was performed to evaluate the antifibrotic
      effect of date flesh extract (DFE) or date pits extract (DPE) via inactivation of
      hepatic stellate cells (HSCs), reducing the levels of inflammatory, fibrotic and
      angiogenic markers. Coffee was used as reference hepatoprotective agent. Liver
      fibrosis was induced by injection of CCl4 (0.4 mL/kg) three times weekly for 8
      weeks. DFE, DPE (6 mL/kg), coffee (300 mg/kg), and combination of coffee + DFE
      and coffee + DPE were given to CCl4-intoxicated rats daily for 8 weeks. DFE, DPE,
      and their combination with coffee attenuated the elevated levels of inflammatory
      cytokines including tumor necrosis factor-alpha, interleukin-6, and interleukin
      1beta. The increased levels of transforming growth factor-beta1 and collagen
      deposition in injured liver were alleviated by both extracts. CCl4-induced
      expression of alpha-smooth muscle actin was suppressed indicating HSCs
      inactivation. Increased angiogenesis was ameliorated as revealed by reduced
      levels and expression of vascular endothelial growth factor and CD31. We
      concluded that DFE or DPE could protect liver via different mechanisms. The
      combination of coffee with DFE or DPE may enhance its antifibrotic effects. 

PMID- 25945107
TI  - Shuang-huang-lian attenuates lipopolysaccharide-induced acute lung injury in mice
      involving anti-inflammatory and antioxidative activities.
AB  - Shuang-Huang-Lian (SHL) is a common traditional Chinese preparation extracted
      from Lonicerae Japonicae Flos, Scutellariae Radix, and Fructus Forsythiae. In
      this study, we demonstrate the anti-inflammatory and antioxidative effects of SHL
      on lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice. SHL
      reduced the lung wet/dry weight ratio, lowered the number of total cells in the
      bronchoalveolar lavage fluid, and decreased the myeloperoxidase activity in lung
      tissues 6 h after LPS treatment. It also inhibited the overproduction of
      proinflammatory cytokines (TNF-alpha, IL-1beta, and IL-6) in the bronchoalveolar
      lavage fluid. Histological studies demonstrated that SHL attenuated LPS-induced
      interstitial edema, hemorrhage, and the infiltration of neutrophils into the lung
      tissue. Moreover, SHL could also enhance the superoxide dismutase and catalase
      activities, increase the reduced glutathione content, and decrease the
      malondialdehyde content. The present results suggest that SHL possesses anti
      inflammatory and antioxidative properties that may protect mice against LPS
      induced ALI. 

PMID- 25945108
TI  - Mori folium and mori fructus mixture attenuates high-fat diet-induced cognitive
      deficits in mice.
AB  - Obesity has become a global health problem, contributing to various diseases
      including diabetes, hypertension, cancer, and dementia. Increasing evidence
      suggests that obesity can also cause neuronal damage, long-term memory loss, and
      cognitive impairment. The leaves and the fruits of Morus alba L., containing
      active phytochemicals, have been shown to possess antiobesity and hypolipidemic
      properties. Thus, in the present study, we assessed their effects on cognitive
      functioning in mice fed a high-fat diet by performing immunohistochemistry, using
      antibodies against c-Fos, synaptophysin, and postsynaptic density protein 95 and
      a behavioral test. C57BL/6 mice fed a high-fat diet for 21 weeks exhibited
      increased body weight, but mice coadministered an optimized Mori Folium and Mori
      Fructus extract mixture (2 : 1; MFE) for the final 12 weeks exhibited significant
      body weight loss. Additionally, obese mice exhibited not only reduced neural
      activity, but also decreased presynaptic and postsynaptic activities, while MFE
      treated mice exhibited recovery of these activities. Finally, cognitive deficits
      induced by the high-fat diet were recovered by cotreatment with MFE in the novel
      object recognition test. Our findings suggest that the antiobesity effects of MFE
      resulted in recovery of the cognitive deficits induced by the high-fat diet by
      regulation of neural and synaptic activities. 

PMID- 25945109
TI  - Effects of diagnostic errors in pattern differentiation and acupuncture
      prescription: a single-blinded, interrater agreement study.
AB  - This study compared the interrater agreement for pattern differentiation and
      acupoints prescription between two groups of human patients simulated with
      different diagnostic outcomes. Patients were simulated using a dataset about
      zangfu patterns and separated into groups (n = 30 each) according to the
      diagnostic outcome determined by a computational model. A questionnaire with 90
      patients was delivered to 6 TCM experts (4-year minimal of clinic experience) who
      were asked to indicate a single pattern (among 73) and 8 acupoints (among 378).
      Interrater agreement was higher for pattern differentiation than for acupuncture
      prescription. Interrater agreement on pattern differentiation was slight for both
      groups with correct (Light's kappa = 0.167, 95% CI = [0.108; 0.254]) and
      incorrect diagnosis (Light's kappa = 0.190, 95% CI = [0.120; 0.286]). Interrater
      agreement on acupuncture prescription was slight for both groups of correct (iota
      = 0.029, 95% CI = [0.015; 0.057]) and incorrect diagnosis (iota = 0.040, 95% CI =
      [0.023; 0.058], P = 0.075). Diagnostic performance of raters yielded the
      following: accuracy = 60.9%, sensitivity = 21.7%, and specificity = 100%. An
      overall improvement in the interrater agreement and diagnostic accuracy was
      observed when the data were analyzed using the internal systems instead of the
      pattern's labels. 

PMID- 25945110
TI  - Phosphodiesterase-1 Inhibitory Activity of Two Flavonoids Isolated from Pistacia
      integerrima J. L. Stewart Galls.
AB  - Pistacia integerrima is one of twenty species among the genus Pistacia. Long horn
      shaped galls that develop on this plant are harvested and used in Ayurveda and
      Indian traditional medicine to make "karkatshringi", a herbal medicine used for
      the treatment of asthma and different disorders of respiratory tract. However,
      until now, the molecular mechanisms of action of "karkatshringi" and its chemical
      characterization are partially known. This study deals with the isolation and
      characterization of the active constituents from the methanolic extract of P.
      integerrima galls and it was also oriented to evaluate in vitro and in silico
      their potential enzymatic inhibitory activity against phosphodiesterase-1 (PDE1),
      a well-known enzyme involved in airway smooth muscle activity and airway
      inflammation. Our results showed that the methanolic extract of P. integerrima
      galls and some of its active constituents [naringenin (1) and 3,5,7,4'
      tetrahydroxy-flavanone (2)] are able in vitro to inhibit PDE1 activity (59.20 +/-
      4.95%, 75.90 +/- 5.90%, and 65.25 +/- 5.25%, resp.) and demonstrate in silico an
      interesting interaction with this enzymatic site. Taken together, our results add
      new knowledge of chemical constituents responsible for the biological activity of
      P. integerrima and contextually legitimate the use of this plant in folk
      medicine. 

PMID- 25945111
TI  - PMC-12, a Prescription of Traditional Korean Medicine, Improves Amyloid beta
      Induced Cognitive Deficits through Modulation of Neuroinflammation.
AB  - PMC-12 is a prescription used in traditional Korean medicine that consists of a
      mixture of four herbal medicines, Polygonum multiflorum, Rehmannia glutinosa,
      Polygala tenuifolia, and Acorus gramineus, which have been reported to have
      various pharmacological effects on age-related neurological diseases. In the
      present study, we investigated whether PMC-12 improves cognitive deficits
      associated with decreased neuroinflammation in an amyloid-beta-(Abeta-) induced
      mouse model and exerts the antineuroinflammatory effects in lipopolysaccharide
      (LPS-) stimulated murine BV2 microglia. Intracerebroventricular injection of
      Abeta 25-35 in mice resulted in impairment in learning and spatial memory,
      whereas this was reversed by oral administration of PMC-12 (100 and 500
      mg/kg/day) in dose-dependent manners. Moreover, PMC-12 reduced the increase of
      Abeta expression and activation of microglia and astrocytes in the Abeta 25-35
      injected brain. Furthermore, quantitative PCR data showed that inflammatory
      mediators were significantly decreased by administration of PMC-12 in Abeta
      injected brains. Consistent with the in vivo data, PMC-12 significantly reduced
      the inflammatory mediators in LPS-stimulated BV2 cells without cell toxicity.
      Moreover, PMC-12 exhibited anti-inflammatory properties via downregulation of
      ERK, JNK, and p38 MAPK pathways. These findings suggest that the protective
      effects of PMC-12 may be mediated by its antineuroinflammatory activities,
      resulting in the attenuation of memory impairment; accordingly, PMC-12 may be
      useful in the prevention and treatment of AD. 

PMID- 25945112
TI  - Structural integration as an adjunct to outpatient rehabilitation for chronic
      nonspecific low back pain: a randomized pilot clinical trial.
AB  - Structural Integration (SI) is an alternative method of manipulation and movement
      education. To obtain preliminary data on feasibility, effectiveness, and adverse
      events (AE), 46 outpatients from Boston area with chronic nonspecific low back
      pain (CNSLBP) were randomized to parallel treatment groups of SI plus outpatient
      rehabilitation (OR) versus OR alone. Feasibility data were acceptable except for
      low compliance with OR and lengthy recruitment time. Intent-to-treat data on
      effectiveness were analyzed by Wilcoxon rank sum, n = 23 per group. Median
      reductions in VAS Pain, the primary outcome, of -26 mm in SI + OR versus 0 in OR
      alone were not significantly different (P = 0.075). Median reductions in RMDQ,
      the secondary outcome, of -2 points in SI + OR versus 0 in OR alone were
      significantly different (P = 0.007). Neither the proportions of participants with
      nor the seriousness of AE were significantly different. SI as an adjunct to OR
      for CNSLBP is not likely to provide additional reductions in pain but is likely
      to augment short term improvements in disability with a low additional burden of
      AE. A more definitive trial is feasible, but OR compliance and recruitment might
      be challenging. This trial is registered with ClinicalTrials.gov (NCT01322399). 

PMID- 25945113
TI  - Antibacterial and Antiproliferative Activities of Plumericin, an Iridoid Isolated
      from Momordica charantia Vine.
AB  - Plumericin, an iridoid lactone, was isolated with relatively high yield from
      Momordica charantia vine using the supercritical fluid extraction (SFE) and the
      separation box (Sepbox) comprising dual combination of high-performance liquid
      chromatography and solid phase extraction. This compound showed antibacterial
      activity against Enterococcus faecalis and Bacillus subtilis with minimum
      inhibitory concentration (MIC) values better than cloxacillin. Plumericin
      potently inhibited proliferation of two leukemic cancer cell lines: they were
      acute and chronic leukemic cancer cell lines, NB4 and K562, with the effective
      doses (ED50) of 4.35 +/- 0.21 and 5.58 +/- 0.35 MUg/mL, respectively. In
      addition, the mechanism of growth inhibition in both cell lines was induced by
      apoptosis, together with G2/M arrest in K562 cells. 

PMID- 25945114
TI  - Evaluation of chemical constituents and important mechanism of pharmacological
      biology in dendrobium plants.
AB  - Dendrobium species, commonly known as "Shihu" or "Huangcao," represents the
      second largest genus of Orchidaceae, which are used commonly as tonic herbs and
      healthy food in many Asian countries. The aim of this paper is to review the
      history, chemistry, and pharmacology of different Dendrobium species on the basis
      of the latest academic literatures found in Google Scholar, PubMed,
      Sciencedirect, Scopus, and SID. 

PMID- 25945115
TI  - Effect of Eugenol against Streptococcus agalactiae and Synergistic Interaction
      with Biologically Produced Silver Nanoparticles.
AB  - Streptococcus agalactiae (group B streptococci (GBS)) is an important infections
      agent in newborns associated with maternal vaginal colonization. Intrapartum
      antibiotic prophylaxis in GBS-colonized pregnant women has led to a significant
      reduction in the incidence of early neonatal infection in various geographic
      regions. However, this strategy may lead to resistance selecting among GBS,
      indicating the need for new alternatives to prevent bacterial transmission and
      even to treat GBS infections. This study reported for the first time the effect
      of eugenol on GBS isolated from colonized women, alone and in combination with
      silver nanoparticles produced by Fusarium oxysporum (AgNPbio). Eugenol showed a
      bactericidal effect against planktonic cells of all GBS strains, and this effect
      appeared to be time-dependent as judged by the time-kill curves and viability
      analysis. Combination of eugenol with AgNPbio resulted in a strong synergistic
      activity, significantly reducing the minimum inhibitory concentration values of
      both compounds. Scanning and transmission electron microscopy revealed fragmented
      cells and changes in bacterial morphology after incubation with eugenol. In
      addition, eugenol inhibited the viability of sessile cells during biofilm
      formation and in mature biofilms. These results indicate the potential of eugenol
      as an alternative for controlling GBS infections. 

PMID- 25945116
TI  - Chronic Treatment with a Water-Soluble Extract from the Culture Medium of
      Ganoderma lucidum Mycelia Prevents Apoptosis and Necroptosis in Hypoxia/Ischemia
      Induced Injury of Type 2 Diabetic Mouse Brain.
AB  - Type 2 diabetes mellitus has been known to increase systemic oxidative stress by
      chronic hyperglycemia and visceral obesity and aggravate cerebral ischemic
      injury. On the basis of our previous study regarding a water-soluble extract from
      the culture medium of Ganoderma lucidum mycelia (designed as MAK), which exerts
      antioxidative and neuroprotective effects, the present study was conducted to
      evaluate the preventive effects of MAK on apoptosis and necroptosis (a programmed
      necrosis) induced by hypoxia/ischemia (H/I) in type 2 diabetic KKAy mice. H/I was
      induced by a combination of unilateral common carotid artery ligation with
      hypoxia (8% O2 for 20 min) and subsequent reoxygenation. Pretreatment with MAK (1
      g/kg, p.o.) for a week significantly reduced H/I-induced neurological deficits
      and brain infarction volume assessed at 24 h of reoxygenation. Histochemical
      analysis showed that MAK significantly suppressed superoxide production, neuronal
      cell death, and vacuolation in the ischemic penumbra, which was accompanied by a
      decrease in the numbers of TUNEL- or cleaved caspase-3-positive cells.
      Furthermore, MAK decreased the expression of receptor-interacting protein kinase
      3 mRNA and protein, a key molecule for necroptosis. These results suggest that
      MAK confers resistance to apoptotic and necroptotic cell death and relieves H/I
      induced cerebral ischemic injury in type 2 diabetic mice. 

PMID- 25945117
TI  - Metabolomics analysis of seminal plasma in infertile males with kidney-yang
      deficiency: a preliminary study.
AB  - Traditional Chinese medicine (TCM) is an important treatment for male
      infertility, and its application to therapy is dependent on differentiation of
      TCM syndromes. This study aims to investigate the changes in metabolites and
      metabolic pathways in infertile males with Kidney-Yang Deficiency syndrome (KYDS)
      via metabolomics approaches. Seminal plasma samples were collected from 18
      infertile males with KYDS and 18 fertile males. Liquid chromatography and mass
      spectrometry were used to characterize metabolomics profiles. Principal component
      analysis (PCA), partial least squares-discriminate analysis (PLS-DA), and pathway
      analysis were used for pattern recognition and metabolite identification. PCA and
      PLS-DA results differentiated the two groups of patients. Forty-one
      discriminating metabolites (18 in positive mode and 23 in negative mode) were
      identified. Seven metabolites were related to five potential metabolic pathways
      associated with biosynthesis and metabolism of aromatic amino acids,
      tricarboxylic acid cycle, and sphingolipid metabolism. The changes in metabolic
      pathways may play an important role in the origin of KYDS-associated male
      infertility. Metabolomics analysis of seminal plasma may be used to differentiate
      TCM syndromes of infertile males, but further research must be conducted. 

PMID- 25945118
TI  - Evaluation of the effects of a combination of Japanese honey and hydrocolloid
      dressing on cutaneous wound healing in male mice.
AB  - The aim of this study was to evaluate the effect of the combined use of Japanese
      honey and hydrocolloid dressing (HCD) on cutaneous wound healing. Mice were
      divided into four groups: the Acacia (Japan) + HCD, Manuka (New Zealand) + HCD,
      Chinese milk vetch (Japan) + HCD, and HCD (control) groups. The mice received two
      full-thickness wounds. The wounds of the HCD group were covered with HCD, whereas
      those of the other groups were treated with 0.1 mL of the relevant type of honey,
      before being covered with HCD. Wound area was significantly smaller in the HCD
      group than in the Acacia + HCD and Manuka + HCD groups on day 13 and days 8-14,
      respectively. Moreover, compared with the HCD group, reepithelialization was
      delayed in the Acacia + HCD group and reepithelialization and collagen deposition
      were delayed in the Chinese milk vetch + HCD and Manuka + HCD groups. These
      results indicate that the combined use of Japanese honey and HCD does not promote
      cutaneous wound healing compared with the use of HCD alone. Thus, this method is
      probably not useful for promoting healing. 

PMID- 25945119
TI  - Partner notification in the context of HIV: an interest-analysis.
AB  - Codes of confidentiality play an essential role in the intimate discourses in
      many learned professions. Codes with various prescriptions exist. The Hippocratic
      Oath for example, prescribes rewards to the secret keeper, for keeping secret
      what ought to be kept secret, and punishments for failing. In public health
      practice, partner notification, arguably is one endeavor that tests the
      durability of this secret keeping doctrine of the health professional. We present
      an interest-analysis of partner notification in the context of HIV service
      rendition. Using principles-based analysis, the interests of the individual, the
      state/public health, and the bioethicist's are discussed. The public health
      interests in partner notification, which are usually backed by state statutes and
      evidence, are premised on the theory that partners are entitled to knowledge.
      This theory posits that knowledge empowers individuals to avoid continuing risks;
      knowledge of infection allows for early treatment; and that knowledgeable
      partners can adapt their behavior to prevent further transmission of infection to
      others. However, persons infected with HIV often have counter interests. For
      instance, an infected person may desire to maintain the privacy of their health
      status from unnecessary disclosure because of the negative impacts of disclosure,
      or because notification without a matching access to HIV prevention and treatment
      services is detrimental. The interest of the bioethicist in this matter is to
      facilitate a resolution of these conflicted interests. Our analysis concludes
      that governmental interests are not absolute in comparison with the interests of
      the individual. We reiterate that any effort to morally balance the benefits of
      partner notification with its burdens ought to first recognize the multivalent
      nature of the interests at play. 

PMID- 25945120
TI  - Research on a pulmonary nodule segmentation method combining fast self-adaptive
      FCM and classification.
AB  - The key problem of computer-aided diagnosis (CAD) of lung cancer is to segment
      pathologically changed tissues fast and accurately. As pulmonary nodules are
      potential manifestation of lung cancer, we propose a fast and self-adaptive
      pulmonary nodules segmentation method based on a combination of FCM clustering
      and classification learning. The enhanced spatial function considers
      contributions to fuzzy membership from both the grayscale similarity between
      central pixels and single neighboring pixels and the spatial similarity between
      central pixels and neighborhood and improves effectively the convergence rate and
      self-adaptivity of the algorithm. Experimental results show that the proposed
      method can achieve more accurate segmentation of vascular adhesion, pleural
      adhesion, and ground glass opacity (GGO) pulmonary nodules than other typical
      algorithms. 

PMID- 25945121
TI  - MRI segmentation of the human brain: challenges, methods, and applications.
AB  - Image segmentation is one of the most important tasks in medical image analysis
      and is often the first and the most critical step in many clinical applications.
      In brain MRI analysis, image segmentation is commonly used for measuring and
      visualizing the brain's anatomical structures, for analyzing brain changes, for
      delineating pathological regions, and for surgical planning and image-guided
      interventions. In the last few decades, various segmentation techniques of
      different accuracy and degree of complexity have been developed and reported in
      the literature. In this paper we review the most popular methods commonly used
      for brain MRI segmentation. We highlight differences between them and discuss
      their capabilities, advantages, and limitations. To address the complexity and
      challenges of the brain MRI segmentation problem, we first introduce the basic
      concepts of image segmentation. Then, we explain different MRI preprocessing
      steps including image registration, bias field correction, and removal of
      nonbrain tissue. Finally, after reviewing different brain MRI segmentation
      methods, we discuss the validation problem in brain MRI segmentation. 

PMID- 25945122
TI  - Mental health and social service needs for mental health service users in Japan:
      a cross-sectional survey of client- and staff-perceived needs.
AB  - BACKGROUND: The appropriate utilization of community services by people with
      mental health difficulties is becoming increasingly important in Japan. The aim
      of the present study was to describe service needs, as perceived by people with
      mental health difficulties living in the community and their service providers.
      We analyzed the difference between two necessity ratings using paired data in
      order to determine implications related to needs assessment for mental health
      services. METHODS: This cross-sectional study used two self-reported
      questionnaires, with one questionnaire administered to mental health service
      users living in the community and another questionnaire to staff members
      providing services to those users at community service facilities. The study was
      conducted in psychiatric social rehabilitation facilities for people with mental
      health difficulties in Japan. The paired client and staff responses rated needs
      for each kind of mental health and social service independently. The 19 services
      listed in the questionnaire included counseling and healthcare, housing, renting,
      daily living, and employment. Overall, 246 individuals with mental health
      difficulties were asked to participate in this study, and after excluding invalid
      responses, 188 client-staff response dyads (76.4% of recruited people, 83.6% of
      people who gave consent) were analyzed in this study. A Wilcoxon matched-pairs
      signed rank test was used to compare the perceived needs, and weighted and
      unweighted Kappa statistics were calculated to assess rating agreement within
      client-staff dyads. RESULTS: Over 75% of participants in our study, who were
      people with mental health difficulties living in the community, regarded each
      type of mental health service as "somewhat necessary," or "absolutely necessary"
      to live in their community. Most clients and staff rated healthcare facilities
      with 24/7 crisis consultation services as necessary. Agreement between client and
      staff ratings of perceived needs for services was low (Kappa = .02 to .26).
      Services regarding housing, renting a place to live, and advocacy had the same
      tendency in that clients perceived a higher need when compared to staff
      perceptions (p < .01). CONCLUSIONS: It is essential for the service providers to
      identify the services that each user needs, engage in dialogue, and involve
      clients in service planning and development.

PMID- 25945123
TI  - The relationship between physical activity, sedentary behaviour and mental health
      in Ghanaian adolescents.
AB  - BACKGROUND: Research development is needed in physical activity and sedentary
      behaviour and their associations with mental health in young people. In Western
      countries the weather is a key contributing factor of sedentary behaviour in
      youth. The likely contributing factor of sedentary behaviour among African youth
      has not been explored. This study examined the association between sedentary
      behaviour and mental health in African young people. METHODS: Participants were
      296 adolescents (150 males, 146 females) aged 13 to 18 years (mean = 14.85 years)
      living in Ghana. Participants' physical activity levels were assessed using the
      Physical Activity Questionnaire for Older Adolescents (PAQ-A) and sedentary
      behaviour, using the Adolescents Sedentary Activity Questionnaire. Depression was
      assessed using the Children Depression Inventory and aspects of self-esteem were
      measured with the Physical Self-worth test and Body Image Silhouette test.
      RESULTS: There was a significant negative correlation between physical activity
      and mental health independent of sedentary behaviour [depression (r =-0.78, p <
      0.001); physical self-worth (r = 0.71, p < 0.001); body dissatisfaction (r =
      0.76, p < 0.001)]. Moreover, sedentary behaviour was significantly associated
      with higher depression (r = 0.68, p < 0.001). Affluence was a significant
      contributing factor of sedentary behaviour in African young people [t (294) =
      7.30, p < 0.001]. CONCLUSION: The present study has found that sedentary
      behaviour is highly prevalent among African adolescents especially among
      adolescents from affluent homes. Low levels of physical activity as well as
      sedentary behaviour is significantly associated with mental health problems among
      African youth, which is consistent with reports from studies among Western young
      people. The present research, therefore, contributes new information to the
      existing literature. Increased physical activities can improve the mental health
      of adolescents.

PMID- 25945124
TI  - Donor caveolin 1 (CAV1) genetic polymorphism influences graft function after
      renal transplantation.
AB  - BACKGROUND: Identification of the culprit genes underlying multifactorial
      diseases is one of the most important current challenges of molecular genetics.
      While recent advances in genomics research have accelerated the discovery of
      susceptibility genes, much remains to be learned about the functions of disease
      associated genetic variants. Recently, Moore and co-workers identified, in the
      donor genome, an association between a common genetic variant (rs4730751) in the
      gene encoding caveolin-1 (CAV1), a major structural component of caveolae, and
      long-term allograft survival. METHODS: Four hundred seventy-five renal recipients
      consecutively transplanted were included in this study. Donor genomic DNA was
      extracted and used to genotype CAV1 rs4730751 Single Nucleotide Polymorphism.
      RESULTS: Patients receiving a graft carrying CAV1 rs4730751 AA genotype displayed
      a significant decrease in estimated glomerular filtration rate and a significant
      increase in serum creatinine in both univariate and multivariate analyzes.
      Moreover, patients receiving a graft with CAV1 AA genotype significantly
      developed more interstitial fibrosis lesions on systematic biopsies performed 3
      months post-transplantation. CONCLUSIONS: Genotyping of CAV1 may be relevant to
      identify patients at risk of adverse renal transplant outcome.

PMID- 25945125
TI  - Chronic obstructive pulmonary disease and heart rate variability: a literature
      update.
AB  - BACKGROUND: The literature indicates that chronic obstructive pulmonary disease
      (COPD) affects cardiac autonomic control. In this study, we conducted a
      literature review in order to investigate the heart rate variability (HRV) in
      COPD subjects. METHODS: A search was performed in Medline database, using the
      link between the keywords: "autonomic nervous system", "cardiovascular system",
      "COPD" and "heart rate variability". RESULTS: The search resulted in a total of
      40 references. Amongst these references, the first exclusion resulted in the
      barring of 29 titles and abstracts, which were not clearly related to the purpose
      of review. This resulted in a total of 11 articles that were then read and
      utilized in the review. The selected studies indicated that there is significant
      reduction of HRV in patients with COPD, characterized by reduction of indices
      that assess parasympathetic activity in addition to dealing with the global
      autonomic modulation. We also established that supervised exercise can reduce
      these harmful effects in COPD patients. Also, it was reported that the use of non
      invasive ventilation in these patients may contribute to the improvement of
      respiratory symptoms, with no impairing, and may even induce positive responses
      in cardiac autonomic regulation. CONCLUSION: The studies indicate a need for
      further investigations to guide future therapies to improve the treatment of
      cardiovascular system in the respiratory diseases.

PMID- 25945126
TI  - Diagnostic accuracy of Bethesda system for reporting thyroid cytopathology: an
      institutional perspective.
AB  - INTRODUCTION: Thyroid swelling is common problem among South Asian women.
      Although benign nodules far outnumber cancerous lesions, the risk of malignancy
      needs to be evaluated preoperatively for which fine needle aspiration cytology
      (FNAC) is widely used. Bethesda system for reporting thyroid cytopathology
      (BSRTC) was introduced to streamline the reporting of thyroid aspirates. We aimed
      to evaluate the disease spectrum of thyroid cytopathology and correlation of
      BSRTC with final histopathology in our setup. METHODS: The study was conducted at
      Histopathology department of Liaquat National Hospital, Karachi, involving 528
      patients with thyroid swelling who underwent FNAC. Out of these 528 cases, 61
      patients subsequently underwent surgical excision. Results of final
      histopathology were correlated with cytologic diagnosis. RESULTS: Mean age of the
      patients included in the study was 39.7 +/- 13(14-84) and male to female ratio
      was 1:3.6. Out of total 528 cases, 403 cases were diagnosed as benign (Bethesda
      2) and 67 were Bethesda 3 (follicular lesion of undetermined significance, FLUS)
      while 22 cases were categorized as either malignant or suspicious for malignancy
      (Bethesda 6 and 5). Histopathologic correlation was done in 61 cases. For
      Bethesda 5 and 6 categories, 100% concordance was found, however for Bethesda 2
      category, 5 out of 45 cases were found to have malignant diagnosis on final
      histopathology. The incidence of malignancy in Bethesda categories 2 through 4
      were 11.1%, 33.4%, 25%, 100% and 100% respectively. Overall accuracy of FNA
      cytology was 80.3% with 64.3% sensitivity and 85.1% specificity. CONCLUSION: Our
      study validated the accuracy of BSRTC in our setup. Therefore we recommend
      routine use of BSRTC for reporting thyroid cytopathology for initial workup of
      patients with thyroid nodule. However, risk of malignancy was found to be
      significantly high in Bethesda 3 category to warrant further workup including
      ultrasound/thyroid scan in addition to repeat FNAC.

PMID- 25945127
TI  - Serum C-peptide assay of patients with hyperglycemic emergencies at the Lagos
      State University Teaching Hospital (LASUTH), Ikeja.
AB  - INTRODUCTION: HE are common acute complications of diabetes mellitus (DM) and
      include diabetic ketoacidosis (DKA), normo-osmolar hyperglycemic state (NHS) and
      hyperosmolar hyperglycemic state (HHS). They contribute a lot to the mortality
      and morbidity of DM. The clinical features include dehydration, hyperglycemia,
      altered mental status and ketosis. The basic mechanism of HE is a reduction in
      the net effective action of circulating insulin, resulting in hyperglycemia and
      ketonemia (in DKA) causing osmotic diuresis and electrolytes loss. Infection is a
      common precipitating factor. Measurement of serum C-peptide provides an accurate
      assessment of residual beta-cell function and is a marker of insulin secretion in
      DM patients. AIM AND OBJECTIVES: To assess the level of pancreatic beta cell
      function in HE patients, using the serum C-peptide. METHODOLOGY: The biodata and
      clinical characteristics of the 99 subjects were collated using a questionnaire.
      All subjects had their serum C-peptide, glucose, electrolytes, urea, creatinine
      levels, urine ketones determined at admission. Results of statistical analysis
      were expressed as mean +/- standard deviation (SD). A p value <0.05 was regarded
      statistically significant. Correlation between levels of serum C-peptide and
      admission blood glucose levels and the duration of DM respectively was done.
      RESULTS: The mean age of the subjects was 51 (SD +/- 16) years and comparable in
      both sexes. Mean duration of DM was 6.3 (SD +/- 7.1) years, with 35% newly
      diagnosed at admission. The types of HE in this study are: DKA (24.7%), NHS
      (36.1%), and HHS (39.2%). Mean blood glucose in this study was 685 mg/dL,
      significantly highest in HHS and lowest in NHS. Mean serum C-peptide level was
      1.6 ng/dL. It was 0.9 ng/dL in subjects with DKA and NHS while 2.7 ng/dL in HHS
      (p>0.05). Main precipitating factors were poor drug compliance, new-onset of DM
      and infection. CONCLUSION: Most (70%) of subjects had poor pancreatic beta cell
      function, this may be a contributory factor to developing HE. Most subjects with
      high C-peptide levels had HHS.

PMID- 25945128
TI  - Brivaracetam, but not ethosuximide, reverses memory impairments in an Alzheimer's
      disease mouse model.
AB  - INTRODUCTION: Recent studies have shown that several strains of transgenic
      Alzheimer's disease (AD) mice overexpressing the amyloid precursor protein (APP)
      have cortical hyperexcitability, and their results have suggested that this
      aberrant network activity may be a mechanism by which amyloid-beta (Abeta) causes
      more widespread neuronal dysfunction. Specific anticonvulsant therapy reverses
      memory impairments in various transgenic mouse strains, but it is not known
      whether reduction of epileptiform activity might serve as a surrogate marker of
      drug efficacy for memory improvement in AD mouse models. METHODS: Transgenic AD
      mice (APP/PS1 and 3xTg-AD) were chronically implanted with dural
      electroencephalography electrodes, and epileptiform activity was correlated with
      spatial memory function and transgene-specific pathology. The antiepileptic drugs
      ethosuximide and brivaracetam were tested for their ability to suppress
      epileptiform activity and to reverse memory impairments and synapse loss in
      APP/PS1 mice. RESULTS: We report that in two transgenic mouse models of AD
      (APP/PS1 and 3xTg-AD), the presence of spike-wave discharges (SWDs) correlated
      with impairments in spatial memory. Both ethosuximide and brivaracetam reduce
      mouse SWDs, but only brivaracetam reverses memory impairments in APP/PS1 mice.
      CONCLUSIONS: Our data confirm an intriguing therapeutic role of anticonvulsant
      drugs targeting synaptic vesicle protein 2A across AD mouse models. Chronic
      ethosuximide dosing did not reverse spatial memory impairments in APP/PS1 mice,
      despite reduction of SWDs. Our data indicate that SWDs are not a reliable
      surrogate marker of appropriate target engagement for reversal of memory
      dysfunction in APP/PS1 mice.

PMID- 25945129
TI  - DNA methylation and gene expression profiles show novel regulatory pathways in
      hepatocellular carcinoma.
AB  - BACKGROUND: Alcohol is a well-known risk factor for hepatocellular carcinoma
      (HCC), but the mechanisms underlying the alcohol-related hepatocarcinogenesis are
      still poorly understood. Alcohol alters the provision of methyl groups within the
      hepatic one-carbon metabolism, possibly inducing aberrant DNA methylation.
      Whether specific pathways are epigenetically regulated in alcohol-associated HCC
      is, however, unknown. The aim of the present study was to investigate the genome
      wide promoter DNA methylation and gene expression profiles in non-viral, alcohol
      associated HCC. From eight HCC patients undergoing curative surgery, array-based
      DNA methylation and gene expression data of all annotated genes were analyzed by
      comparing HCC tissue and homologous cancer-free liver tissue. RESULTS: After
      merging the DNA methylation with gene expression data, we identified 159
      hypermethylated-repressed, 30 hypomethylated-induced, 49 hypermethylated-induced,
      and 56 hypomethylated-repressed genes. Notably, promoter DNA methylation emerged
      as a novel regulatory mechanism for the transcriptional repression of genes
      controlling the retinol metabolism (ADH1A, ADH1B, ADH6, CYP3A43, CYP4A22, RDH16),
      iron homeostasis (HAMP), one-carbon metabolism (SHMT1), and genes with a
      putative, newly identified function as tumor suppressors (FAM107A, IGFALS, MT1G,
      MT1H, RNF180). CONCLUSIONS: A genome-wide DNA methylation approach merged with
      array-based gene expression profiles allowed identifying a number of novel,
      epigenetically regulated candidate tumor-suppressor genes in alcohol-associated
      hepatocarcinogenesis. Retinol metabolism genes and SHMT1 are also epigenetically
      regulated through promoter DNA methylation in alcohol-associated HCC. Due to the
      reversibility of epigenetic mechanisms by environmental/nutritional factors,
      these findings may open up to novel interventional strategies for
      hepatocarcinogenesis prevention in HCC related to alcohol, a modifiable dietary
      component.

PMID- 25945130
TI  - Racial differences in IGF1 methylation and birth weight.
AB  - BACKGROUND: The birth weight of Black neonates in the United States is
      consistently smaller than that of their White counterparts. Epigenetic
      differences between the races may be involved in such disparities. The goal of
      these analyses was to model the role of IGF1 methylation in mediating the
      association between race and birth weight. Data was collected on a cohort of 87
      live born infants. IGF1 methylation was measured in DNA isolated from the
      mononuclear fraction of umbilical cord blood collected after delivery.
      Quantitative, loci-specific methylation was assessed using the Infinium
      HumanMethylation27 BeadArray (Illumina Inc., San Diego, CA). Locus specific
      methylation of the IGF1 CpG site was validated on a subset of the original sample
      (N = 61) using pyrosequencing. Multiple linear regression was used to examine
      relationships between IGF1 methylation, race, and birth weight. A formal
      mediation analysis was then used to estimate the relationship of IGF1 methylation
      to race and birth weight. RESULTS: Black race was associated with a 7.45%
      decrease in gestational age-adjusted birth weight (aBW) (P = 0.04) and Black
      infants had significantly higher IGF1 methylation than non-Black infants (P <
      0.05). A one standard deviation increase in IGF1 methylation was associated with
      a 3.32% decrease in aBW (P = 0.02). Including IGF1 methylation as a covariate,
      the effect of Black race on aBW was attenuated. A formal mediation analysis
      showed that the controlled direct effect of Black race on aBW was -6.26% (95% CI
      = -14.15, 1.06); the total effect of Black race on IGF1 methylation was -8.12%
      (95% CI = -16.08, -0.55); and the natural indirect effect of Black race on aBW
      through IGF1 methylation was -1.86% (95% CI = -5.22, 0.18). CONCLUSION: The
      results of the mediation analysis along with the multivariable regression
      analyses suggest that IGF1 methylation may partially mediate the relationship
      between Black race and aBW. Such epigenetic differences may be involved in racial
      disparities observed in perinatal outcomes.

PMID- 25945131
TI  - Comparison of HPV genotyping and methylated ZNF582 as triage for women with
      equivocal liquid-based cytology results.
AB  - INTRODUCTION: The interpretation of equivocal Papanicolaou (Pap) smear results
      remains challenging, even with the addition of the high-risk human papillomavirus
      test (HPV-HR). Recently, methylated zinc finger protein 582 (ZNF582) (ZNF582 (m)
      ) was reported to be highly associated with cervical cancer. In this study, we
      compared the performance of ZNF582 (m) detection and HPV-HR genotyping in the
      triage of cervical atypical squamous cell of undetermined significance (ASC-US)
      and atypical squamous cell - cannot exclude a high-grade lesion (ASC-H). CASE
      DESCRIPTION: Two hundred and forty-two subjects with equivocal papanicolaou smear
      (Pap smear) results were recruited in this hospital-based and case-controlled
      study. The residual cervical cells in liquid-based cytological test (LBC)
      containers were used for genomic DNA extraction and then for ZNF582 (m) and HPV
      HR detection. The level of ZNF582 (m) was quantified by real-time methylation
      specific PCR after bisulfite conversion. The HPV-HR test was performed by using a
      nested multiplex PCR (NMPCR) assay that combines degenerate E6/E7 consensus
      primers and HPV type-specific primers. DISCUSSION AND EVALUATION: Significant
      associations were observed between ZNF582 (m) and the risk of cervical
      intraepithelial neoplasia grade 3 or higher (CIN3+; odds ratio = 15.52, 95%
      confidence interval (CI): 7.73 to 31.18). The sensitivity and specificity of
      ZNF582 (m) for women with CIN3+ were 82.43% and 76.79%, respectively. High
      sensitivity (99.33%) but low specificity (38.76%) was observed for HPV-HR. When
      combining both positive results of ZNF582 (m) and HPV-HR, the sensitivity and
      specificity were 82.43% and 81.55%, respectively. The sensitivity and specificity
      of ZNF582 (m) or HPV-16/18 were 89.19% and 70.24%, respectively. However, the
      sensitivity and specificity of ZNF582 (m) combined with HPV-16/18 (both ZNF582
      (m) and HPV-16/18 positive results) were 59.46% and 94.64%, respectively.
      CONCLUSIONS: ZNF582 (m) provides a promising triage tool for women with ASC. To
      effectively manage ASC patients, a new strategy co-testing for ZNF582 (m) and HPV
      16/18 genotyping was proposed. This strategy could reduce the number of patients
      referred for colposcopic examination and thus provide a feasible follow-up
      solution in the regions where colposcopy is not readily available. This strategy
      could also prevent women from experiencing unnecessary anxiety caused by HPV-HR.

PMID- 25945132
TI  - Development of low-fluorescence thick photoresist for high-aspect-ratio
      microstructure in bio-application.
AB  - In this study, we propose and evaluate a novel low-auto-fluorescence photoresist
      (SJI photoresist) for bio-application, e.g., in gene analysis and cell assay. The
      spin-coated SJI photoresist has a wide thickness range of ten to several hundred
      micrometers, and photoresist microstructures with an aspect ratio of over 7 and
      micropatterns of less than 2 MUm are successfully fabricated. The emission
      spectrum intensity of the SJI photoresist is found to be over 80% less than that
      of the widely used SU-8 photoresist. To evaluate the validity of using the
      proposed photoresist in bio-application for fluorescence observation, we
      demonstrate a chromosome extension device composed of the SJI photoresist. The
      normalized contrast ratio of the SJI photoresist exhibits a 50% improvement over
      that of the SU-8 photoresist; thus, the SJI photoresist is a versatile tool for
      bio-application. 

PMID- 25945133
TI  - Measurement of single leukemia cell's density and mass using optically induced
      electric field in a microfluidics chip.
AB  - We present a method capable of rapidly (~20 s) determining the density and mass
      of a single leukemic cell using an optically induced electrokinetics (OEK)
      platform. Our team had reported recently on a technique that combines
      sedimentation theory, computer vision, and micro particle manipulation techniques
      on an OEK microfluidic platform to determine the mass and density of micron-scale
      entities in a fluidic medium; the mass and density of yeast cells were accurately
      determined in that prior work. In the work reported in this paper, we further
      refined the technique by performing significantly more experiments to determine a
      universal correction factor to Stokes' equation in expressing the drag force on a
      microparticle as it falls towards an infinite plane. Specifically, a theoretical
      model for micron-sized spheres settling towards an infinite plane in a
      microfluidic environment is presented, and which was validated experimentally
      using five different sizes of micro polystyrene beads. The same sedimentation
      process was applied to two kinds of leukemic cancer cells with similar sizes in
      an OEK platform, and their density and mass were determined accordingly. Our
      tests on mouse lymphocytic leukemia cells (L1210) and human leukemic cells (HL
      60) have verified the practical viability of this method. Potentially, this new
      method provides a new way of measuring the volume, density, and mass of a single
      cell in an accurate, selective, and repeatable manner. 

PMID- 25945134
TI  - Entry effects of droplet in a micro confinement: Implications for deformation
      based circulating tumor cell microfiltration.
AB  - Deformation-based circulating tumor cell (CTC) microchips are a representative
      diagnostic device for early cancer detection. This type of device usually
      involves a process of CTC trapping in a confined microgeometry. Further
      understanding of the CTC flow regime, as well as the threshold passing-through
      pressure, is a key to the design of deformation-based CTC filtration devices. In
      the present numerical study, we investigate the transitional deformation and
      pressure signature from surface tension dominated flow to viscous shear stress
      dominated flow using a droplet model. Regarding whether CTC fully blocks the
      channel inlet, we observe two flow regimes: CTC squeezing and shearing regime. By
      studying the relation of CTC deformation at the exact critical pressure point for
      increasing inlet velocity, three different types of cell deformation are
      observed: (1) hemispherical front, (2) parabolic front, and (3) elongated CTC co
      flowing with carrier media. Focusing on the circular channel, we observe a first
      increasing and then decreasing critical pressure change with increasing flow
      rate. By pressure analysis, the concept of optimum velocity is proposed to
      explain the behavior of CTC filtration and design optimization of CTC filter.
      Similar behavior is also observed in channels with symmetrical cross sections
      like square and triangular but not in rectangular channels which only results in
      decreasing critical pressure. 

PMID- 25945135
TI  - Enhanced single-cell printing by acoustophoretic cell focusing.
AB  - Recent years have witnessed a strong trend towards analysis of single-cells. To
      access and handle single-cells, many new tools are needed and have partly been
      developed. Here, we present an improved version of a single-cell printer which is
      able to deliver individual single cells and beads encapsulated in free-flying
      picoliter droplets at a single-bead efficiency of 96% and with a throughput of
      more than 10 beads per minute. By integration of acoustophoretic focusing, the
      cells could be focused in x and y direction. This way, the cells were lined-up in
      front of a 40 MUm nozzle, where they were analyzed individually by an optical
      system prior to printing. In agreement with acoustic simulations, the focusing of
      10 MUm beads and Raji cells has been achieved with an efficiency of 99% (beads)
      and 86% (Raji cells) to a 40 MUm wide center region in the 1 mm wide microfluidic
      channel. This enabled improved optical analysis and reduced bead losses. The loss
      of beads that ended up in the waste (because printing them as single beads
      arrangements could not be ensured) was reduced from 52% +/- 6% to 28% +/- 1%. The
      piezoelectric transducer employed for cell focusing could be positioned on an
      outer part of the device, which proves the acoustophoretic focusing to be
      versatile and adaptable. 

PMID- 25945136
TI  - Microfluidic-based speckle analysis for sensitive measurement of erythrocyte
      aggregation: A comparison of four methods for detection of elevated erythrocyte
      aggregation in diabetic rat blood.
AB  - Biochemical alterations in the plasma and red blood cell (RBC) membrane of
      diabetic blood lead to excessive erythrocyte aggregation (EA). EA would
      significantly impede the blood flow and increase the vascular flow resistance
      contributing to peripheral vascular diseases. In this study, a simple
      microfluidic-based method is proposed to achieve sensitive detection of
      hyperaggregation. When a blood sample is delivered into the device, images of
      blood flows are obtained with a short exposure time for a relatively long
      measuring time. A micro-particle image velocimetry technique was employed to
      monitor variation of the flow rate of blood as a function of time. Given that EA
      formation in the channel creates clear speckle patterns, the EA extent can be
      estimated by calculating a speckle area (ASpeckle) through a normalized
      autocovariance function. The hematocrit effect is assessed by comparing optical
      images transmitted through blood samples. EA variations caused by dextran
      treatment are quantitatively evaluated using characteristic time (lambdaSpeckle)
      obtained by fitting the variations of ASpeckle. Other indices including number of
      RBCs in an aggregate (NRBC), characteristic time of erythrocyte sedimentation
      rate (lambdaESR), and aggregation index estimated from ultrasound signals
      (AIEcho) are determined under different EA conditions using conventional
      techniques. The four different methods are applied to diabetic blood samples to
      compare their indices under hyperaggregation conditions. It is found that the
      proposed method can detect variation of EA reasonably, compared with conventional
      measurement techniques. These experimental demonstrations support the notion that
      the proposed method is capable of effectively monitoring the biophysical
      properties of diabetic blood. 

PMID- 25945137
TI  - Effects of hydraulic pressure on cardiomyoblasts in a microfluidic device.
AB  - We employed a microfluidic device to study the effects of hydraulic pressure on
      cardiomyoblast H9c2. The 170 mm Hg pressure increased the cellular area and the
      expression of atrial natriuretic peptide. With the same device, we demonstrated
      that the effects of hydraulic pressure on the cardiomyoblast could be reduced by
      the inhibitor of focal adhesion kinase. This mechanical-chemical antagonism could
      lead to a potential therapeutic strategy of hypertension-induced cardiac
      hypertrophy. 

PMID- 25945138
TI  - Evaluation of the Kirkwood approximation for the diffusivity of channel-confined
      DNA chains in the de Gennes regime.
AB  - We use Brownian dynamics with hydrodynamic interactions to calculate both the
      Kirkwood (short-time) diffusivity and the long-time diffusivity of DNA chains
      from free solution down to channel confinement in the de Gennes regime. The
      Kirkwood diffusivity in confinement is always higher than the diffusivity
      obtained from the mean-squared displacement of the center-of-mass, as is the case
      in free solution. Moreover, the divergence of the local diffusion tensor, which
      is non-zero in confinement, makes a negligible contribution to the latter
      diffusivity in confinement. The maximum error in the Kirkwood approximation in
      our simulations is about 2% for experimentally relevant simulation times. The
      error decreases with increasing confinement, consistent with arguments from blob
      theory and the molecular-weight dependence of the error in free solution. In
      light of the typical experimental errors in measuring the properties of channel
      confined DNA, our results suggest that the Kirkwood approximation is sufficiently
      accurate to model experimental data. 

PMID- 25945139
TI  - Electroosmotic flow hysteresis for dissimilar ionic solutions.
AB  - Electroosmotic flow (EOF) with two or more fluids is commonly encountered in
      various microfluidics applications. However, no investigation has hitherto been
      conducted to investigate the hysteretic or flow direction-dependent behavior
      during the displacement flow of solutions with dissimilar ionic species. In this
      investigation, electroosmotic displacement flow involving dissimilar ionic
      solutions was studied experimentally through a current monitoring method and
      numerically through finite element simulations. The flow hysteresis can be
      characterized by the turning and displacement times; turning time refers to the
      abrupt gradient change of current-time curve while displacement time is the time
      for one solution to completely displace the other solution. Both experimental and
      simulation results illustrate that the turning and displacement times for a
      particular solution pair can be directional-dependent, indicating that the flow
      conditions in the microchannel are not the same in the two different flow
      directions. The mechanics of EOF hysteresis was elucidated through the
      theoretical model which includes the ionic mobility of each species, a major
      governing parameter. Two distinct mechanics have been identified as the causes
      for the EOF hysteresis involving dissimilar ionic solutions: the
      widening/sharpening effect of interfacial region between the two solutions and
      the difference in ion concentration distributions (and thus average zeta
      potentials) in different flow directions. The outcome of this investigation
      contributes to the fundamental understanding of flow behavior in microfluidic
      systems involving solution pair with dissimilar ionic species. 

PMID- 25945140
TI  - Rapid microfluidic immunoassay for surveillance and diagnosis of Cryptosporidium
      infection in human immunodeficiency virus-infected patients.
AB  - Cryptosporidiosis has been reported to be associated with HIV/acquired immune
      deficiency syndrome, which greatly reduces the quality of life and shortens the
      life expectancy of HIV-infected patients. In order to properly treat the infected
      patients, accurate and automatic diagnostic tools need to be developed. In this
      study, a novel microfluidic immunochip system was presented for the surveillance
      and the rapid detection of Cryptosporidium infection in 190 HIV-infected patients
      from Guangxi, China, using the P23 antigen of Cryptosporidium. The procedure of
      detection can be completed within 10 min with 2 MUl sample consumption. The
      system also was evaluated using the standard ELISA method. Among 190 HIV-infected
      individuals, the rate of P23 positivity was 13.7%. Seropositivity in HIV-infected
      individuals was higher in female patients. The seropositivity to P23 was higher
      in HIV-infected individuals with high viral load, although the difference was
      statistically insignificant. Significantly higher Cryptosporidium seropositivity
      was observed in HIV-infected individuals with a CD4(+) T-cell count of <200
      cells/MUl than in those with >=200 cells/MUl. Our results also demonstrate that a
      lower CD4(+) T-cell count may reflect an increased accumulated risk for
      cryptosporidiosis. The detection system was further validated using the standard
      ELISA method and good correlation between the two methods was found (r = 0.80).
      Under the same sensitivity, this new microfluidic chip device had a specificity
      of 98.2%. This developed system may provide a powerful platform for the fast
      screening of Cryptospordium infection in HIV-infected patients. 

PMID- 25945141
TI  - Collagen-based brain microvasculature model in vitro using three-dimensional
      printed template.
AB  - We present an engineered three-dimensional (3D) in vitro brain microvasculature
      system embedded within the bulk of a collagen matrix. To create a hydrogel
      template for the functional brain microvascular structure, we fabricated an array
      of microchannels made of collagen I using microneedles and a 3D printed frame. By
      culturing mouse brain endothelial cells (bEnd.3) on the luminal surface of
      cylindrical collagen microchannels, we reconstructed an array of brain
      microvasculature in vitro with circular cross-sections. We characterized the
      barrier function of our brain microvasculature by measuring transendothelial
      permeability of 40 kDa fluorescein isothiocyanate-dextran (Stoke's radius of ~4.5
      nm), based on an analytical model. The transendothelial permeability decreased
      significantly over 3 weeks of culture. We also present the disruption of the
      barrier function with a hyperosmotic mannitol as well as a subsequent recovery
      over 4 days. Our brain microvasculature model in vitro, consisting of system-in
      hydrogel combined with the widely emerging 3D printing technique, can serve as a
      useful tool not only for fundamental studies associated with blood-brain barrier
      in physiological and pathological settings but also for pharmaceutical
      applications. 

PMID- 25945142
TI  - Digital microfluidic three-dimensional cell culture and chemical screening
      platform using alginate hydrogels.
AB  - Electro wetting-on-dielectric (EWOD) digital microfluidics (DMF) can be used to
      develop improved chemical screening platforms using 3-dimensional (3D) cell
      culture. Alginate hydrogels are one common method by which a 3D cell culture
      environment is created. This paper presents a study of alginate gelation on EWOD
      DMF and investigates designs to obtain uniform alginate hydrogels that can be
      repeatedly addressed by any desired liquids. A design which allows for gels to be
      retained in place during liquid delivery and removal without using any physical
      barriers or hydrophilic patterning of substrates is presented. A proof of concept
      screening platform is demonstrated by examining the effects of different
      concentrations of a test chemical on 3D cells in alginate hydrogels. In addition,
      the temporal effects of the various chemical concentrations on different hydrogel
      posts are demonstrated, thereby establishing the benefits of an EWOD DMF 3D cell
      culture and chemical screening platform using alginate hydrogels. 

PMID- 25945143
TI  - Fabrication of nanochannels on polystyrene surface.
AB  - Solvent-induced nanocrack formation on polystyrene surface is investigated
      experimentally. Solubility parameter and diffusion coefficient of alcohols are
      employed to elucidate the swelling and cracking processes as well as the crack
      size. Experimental results show that the crack size increases with the heating
      temperature, heating time, and the concentration and volume of the alcohols. A
      guideline on fabricating single smaller nanocracks on polymers by solvent-induced
      method is provided. Nanocracks of approximately 64 nm in width and 17.4 nm in
      depth were created and replicated onto PDMS (polydimethylsiloxane) slabs to form
      nanochannels. 

PMID- 25945145
TI  - Rapid bench-top fabrication of poly(dimethylsiloxane)/polystyrene microfluidic
      devices incorporating high-surface-area sensing electrodes.
AB  - The development of widely applicable point-of-care sensing and diagnostic devices
      can benefit from simple and inexpensive fabrication techniques that expedite the
      design, testing, and implementation of lab-on-a-chip devices. In particular,
      electrodes integrated within microfluidic devices enable the use of
      electrochemical techniques for the label-free detection of relevant analytes.
      This work presents a novel, simple, and cost-effective bench-top approach for the
      integration of high surface area three-dimensional structured electrodes
      fabricated on polystyrene (PS) within poly(dimethylsiloxane) (PDMS)-based
      microfluidics. Optimization of PS-PDMS bonding results in integrated devices that
      perform well under pressure and fluidic flow stress. Furthermore, the fabrication
      and bonding processes are shown to have no effect on sensing electrode
      performance. Finally, the on-chip sensing capabilities of a three-electrode
      electrochemical cell are demonstrated with a model redox compound, where the high
      surface area structured electrodes exhibit ultra-high sensitivity. We propose
      that the developed approach can significantly expedite and reduce the cost of
      fabrication of sensing devices where arrays of functionalized electrodes can be
      used for point-of-care analysis and diagnostics. 

PMID- 25945144
TI  - Core-shell hydrogel beads with extracellular matrix for tumor spheroid formation.
AB  - Creating multicellular tumor spheroids is critical for characterizing anticancer
      treatments since they may provide a better model of the tumor than conventional
      monolayer culture. Moreover, tumor cell interaction with the extracellular matrix
      can determine cell organization and behavior. In this work, a microfluidic system
      was used to form cell-laden core-shell beads which incorporate elements of the
      extracellular matrix and support the formation of multicellular spheroids. The
      bead core (comprising a mixture of alginate, collagen, and reconstituted basement
      membrane, with gelation by temperature control) and shell (comprising alginate
      hydrogel, with gelation by ionic crosslinking) were simultaneously formed through
      flow focusing using a cooled flow path into the microfluidic chip. During droplet
      gelation, the alginate acts as a fast-gelling shell which aids in preventing
      droplet coalescence and in maintaining spherical droplet geometry during the
      slower gelation of the collagen and reconstituted basement membrane components as
      the beads warm up. After droplet gelation, the encapsulated MCF-7 cells
      proliferated to form uniform spheroids when the beads contained all three
      components: alginate, collagen, and reconstituted basement membrane. The dose
      dependent response of the MCF-7 cell tumor spheroids to two anticancer drugs,
      docetaxel and tamoxifen, was compared to conventional monolayer culture. 

PMID- 25945146
TI  - A low cost design and fabrication method for developing a leak proof paper based
      microfluidic device with customized test zone.
AB  - This article describes a fabrication process for the generation of a leak proof
      paper based microfluidic device and a new design strategy for convenient
      incorporation of externally prepared test zones. Briefly, a negative
      photolithographic method was used to prepare the device with a partial
      photoresist layer on the rear of the device to block the leakage of sample.
      Microscopy and Field Emission Scanning Electron Microscopy data validated the
      formation of the photoresist layer. The partial layer of photoresist on the
      device channel limits sample volume to 7 +/- 0.2 MUl as compared to devices
      without the partial photoresist layer which requires a larger sample volume of 10
      +/- 0.1 MUl. The design prototype with a customized external test zone exploits
      the channel protrusions on the UV exposed photoresist treated paper to bridge the
      externally applied test zone to the sample and absorbent zones. The partially
      laminated device with an external test zone has a comparatively low wicking speed
      of 1.8 +/- 0.9 mm/min compared to the completely laminated device with an inbuilt
      test zone (3.3 +/- 1.2 mm/min) which extends the reaction time between the
      analyte and reagents. The efficacy of the prepared device was studied with
      colorimetric assays for the non-specific detection of protein by tetrabromophenol
      blue, acid/base with phenolphthalein indicator, and specific detection of
      proteins using the HRP-DAB chemistry. The prepared device has the potential for
      leak proof detection of analyte, requires low sample volume, involves reduced
      cost of production (~$0.03, excluding reagent and lamination cost), and enables
      the integration of customized test zones. 

PMID- 25945147
TI  - Pulmonary monoclonal antibody delivery via a portable microfluidic nebulization
      platform.
AB  - Nebulizers have considerable advantages over conventional inhalers for pulmonary
      drug administration, particularly because they do not require coordinated breath
      actuation to generate and deliver the aerosols. Nevertheless, besides being less
      amenable to miniaturization and hence portability, some nebulizers are prone to
      denature macromolecular drugs due to the large forces generated during
      aerosolization. Here, we demonstrate a novel portable acoustomicrofluidic device
      capable of nebulizing epidermal growth factor receptor (EGFR) monoclonal
      antibodies into a fine aerosol mist with a mass median aerodynamic diameter of
      approximately 1.1 MUm, optimal for deep lung deposition via inhalation. The
      nebulized monoclonal antibodies were tested for their stability, immunoactivity,
      and pharmacological properties, which confirmed that nebulization did not cause
      significant degradation of the antibody. In particular, flow cytometry
      demonstrated that the antigen binding capability of the antibody is retained and
      able to reduce phosphorylation in cells overexpressing the EGFR, indicating that
      the aerosols generated by the device were loaded with stable and active
      monoclonal antibodies. The delivery of antibodies via inhalation, particularly
      for the treatment of lung cancer, is thus expected to enhance the efficacy of
      this protein therapeutic by increasing the local concentration where they are
      needed. 

PMID- 25945148
TI  - Sleep deprivation and oxidative stress in animal models: a systematic review.
AB  - Because the function and mechanisms of sleep are partially clear, here we applied
      a meta-analysis to address the issue whether sleep function includes
      antioxidative properties in mice and rats. Given the expansion of the knowledge
      in the sleep field, it is indeed ambitious to describe all mammals, or other
      animals, in which sleep shows an antioxidant function. However, in this paper we
      reviewed the current understanding from basic studies in two species to drive the
      hypothesis that sleep is a dynamic-resting state with antioxidative properties.
      We performed a systematic review of articles cited in Medline, Scopus, and Web of
      Science until March 2015 using the following search terms: Sleep or sleep
      deprivation and oxidative stress, lipid peroxidation, glutathione, nitric oxide,
      catalase or superoxide dismutase. We found a total of 266 studies. After
      inclusion and exclusion criteria, 44 articles were included, which are presented
      and discussed in this study. The complex relationship between sleep duration and
      oxidative stress is discussed. Further studies should consider molecular and
      genetic approaches to determine whether disrupted sleep promotes oxidative
      stress. 

PMID- 25945150
TI  - Age-related responses in circulating markers of redox status in healthy
      adolescents and adults during the course of a training macrocycle.
AB  - Redox status changes during an annual training cycle in young and adult track and
      field athletes and possible differences between the two age groups were assessed.
      Forty-six individuals (24 children and 22 adults) were assigned to four groups:
      trained adolescents, (TAD, N = 13), untrained adolescents (UAD, N = 11), trained
      adults (TA, N = 12), and untrained adults (UA, N = 10). Aerobic capacity and
      redox status related variables [total antioxidant capacity (TAC), glutathione
      (GSH), catalase activity, TBARS, protein carbonyls (PC), uric acid, and
      bilirubin] were assessed at rest and in response to a time-trial bout before
      training, at mid- and posttraining. TAC, catalase activity, TBARS, PC, uric acid,
      and bilirubin increased and GSH declined in all groups in response to acute
      exercise independent of training status and age. Training improved aerobic
      capacity, TAC, and GSH at rest and in response to exercise. Age affected basal
      and exercise-induced responses since adults demonstrated a greater TAC and GSH
      levels at rest and a greater rise of TBARS, protein carbonyls, and TAC and
      decline of GSH in response to exercise. Catalase activity, uric acid, and
      bilirubin responses were comparable among groups. These results suggest that
      acute exercise, age, and training modulate the antioxidant reserves of the body. 

PMID- 25945153
TI  - N = 1.

PMID- 25945151
TI  - Smooth muscle specific overexpression of p22phox potentiates carotid artery wall
      thickening in response to injury.
AB  - We hypothesized that transgenic mice overexpressing the p22(phox) subunit of the
      NADPH oxidase selectively in smooth muscle (Tg(p22smc)) would exhibit an
      exacerbated response to transluminal carotid injury compared to wild-type mice.
      To examine the role of reactive oxygen species (ROS) as a mediator of vascular
      injury, the injury response was quantified by measuring wall thickness (WT) and
      cross-sectional wall area (CSWA) of the injured and noninjured arteries in both
      Tg(p22smc) and wild-type animals at days 3, 7, and 14 after injury. Akt, p38
      MAPK, and Src activation were evaluated at the same time points using Western
      blotting. WT and CSWA following injury were significantly greater in Tg(p22smc)
      mice at both 7 and 14 days after injury while noninjured contralateral carotids
      were similar between groups. Apocynin treatment attenuated the injury response in
      both groups and rendered the response similar between Tg(p22smc) mice and wild
      type mice. Following injury, carotid arteries from Tg(p22smc) mice demonstrated
      elevated activation of Akt at day 3, while p38 MAPK and Src activation was
      elevated at day 7 compared to wild-type mice. Both increased activation and
      temporal regulation of these signaling pathways may contribute to enhanced
      vascular growth in response to injury in this transgenic model of elevated
      vascular ROS. 

PMID- 25945149
TI  - Inhibition of adenylyl cyclase type 5 increases longevity and healthful aging
      through oxidative stress protection.
AB  - Mice with disruption of adenylyl cyclase type 5 (AC5 knockout, KO) live a third
      longer than littermates. The mechanism, in part, involves the MEK/ERK pathway,
      which in turn is related to protection against oxidative stress. The AC5 KO model
      also protects against diabetes, obesity, and the cardiomyopathy induced by aging,
      diabetes, and cardiac stress and also demonstrates improved exercise capacity.
      All of these salutary features are also mediated, in part, by oxidative stress
      protection. For example, chronic beta adrenergic receptor stimulation induced
      cardiomyopathy was rescued by AC5 KO. Conversely, in AC5 transgenic (Tg) mice,
      where AC5 is overexpressed in the heart, the cardiomyopathy was exacerbated and
      was rescued by enhancing oxidative stress resistance. Thus, the AC5 KO model,
      which resists oxidative stress, is uniquely designed for clinical translation,
      since it not only increases longevity and exercise, but also protects against
      diabetes, obesity, and cardiomyopathy. Importantly, inhibition of AC5's action to
      prolong longevity and enhance healthful aging, as well as its mechanism through
      resistance to oxidative stress, is unique among all of the nine AC isoforms. 

PMID- 25945154
TI  - Key Strategic Trends that Impact Healthcare Decision-Making and Stakeholder Roles
      in the New Marketplace.

PMID- 25945152
TI  - The pleiotropic effect of physical exercise on mitochondrial dynamics in aging
      skeletal muscle.
AB  - Decline in human muscle mass and strength (sarcopenia) is one of the principal
      hallmarks of the aging process. Regular physical exercise and training programs
      are certain powerful stimuli to attenuate the physiological skeletal muscle
      alterations occurring during aging and contribute to promote health and well
      being. Although the series of events that led to these muscle adaptations are
      poorly understood, the mechanisms that regulate these processes involve the
      "quality" of skeletal muscle mitochondria. Aerobic/endurance exercise helps to
      maintain and improve cardiovascular fitness and respiratory function, whereas
      strength/resistance-exercise programs increase muscle strength, power
      development, and function. Due to the different effect of both exercises in
      improving mitochondrial content and quality, in terms of biogenesis, dynamics,
      turnover, and genotype, combined physical activity programs should be
      individually prescribed to maximize the antiaging effects of exercise. 

PMID- 25945156
TI  - Editor's Note: Journal Overview.

PMID- 25945155
TI  - High quality draft genome sequence of the heavy metal resistant bacterium
      Halomonas zincidurans type strain B6(T).
AB  - Halomonas zincidurans strain B6(T) was isolated from a deep-sea heavy metal rich
      sediment from the South Atlantic Mid-Ocean Ridge. The strain showed significant
      resistance to heavy metals, especially to zinc. Here we describe the genome
      sequence and annotation, as well as the features, of the organism. The genome
      contains 3,325 protein-coding genes (2,848 with predicted functions), 61 tRNA
      genes and 6 rRNA genes. H. zincidurans strain B6(T) encodes 31 genes related to
      heavy metal resistance. And HGT may play an important role in its adaption to the
      heavy metal rich environment. H. zincidurans strain B6(T) may have potential
      applications in the bioremediation of heavy metal-contaminated environments. 

PMID- 25945157
TI  - The impact of an application of telerehabilitation technology on caregiver
      burden.
AB  - The objective of this research was to assess the effects of an application of
      telerehabilitation reducing time and financial obligation on caregiver burden
      among eleven caregivers of elderly persons with Parkinson's disease. Clients
      (care receivers) participated in speech therapy delivered via videophones in
      their homes; the protocol required 16 treatments delivered four times a week for
      four weeks. At the conclusion of treatment, caregivers completed a structured
      interview about the impact of telerehabilitation on time and financial aspects of
      the burden of care. On average, this speech therapy protocol delivered by
      videophones saved 48 hours of time, more than 92 hours of work time, and $1024
      for each caregiver. Savings were significant and previous research demonstrated
      nearly equal outcomes using the videophone delivery method. Implications for
      practice and research are discussed. 

PMID- 25945158
TI  - In-home telerehabilitation for post-knee arthroplasty: a pilot study.
AB  - The purpose of this study was to investigate the efficacy of in-home
      telerehabilitation as an alternative to conventional rehabilitation services
      following knee arthroplasty. Five community-living elders who had knee
      arthroplasty were recruited prior to discharge from an acute care hospital. A
      pre/post-test design without a control group was used for this pilot study.
      Telerehabilitation sessions (16) were conducted by two trained physiotherapists
      from a service center to the patient's home using H264 videoconference CODECs
      (Tandberg 550 MXP) connected at 512 Kb?s. Disability (range of motion, balance
      and lower body strength) and function (locomotor performance in walking and
      functional autonomy) were measured in face-to-face evaluations prior to and at
      the end of the treatments by a neutral evaluator. The satisfaction of the health
      care professional and patient was measured by questionnaire. Results are as
      follows. One participant was lost during follow-up. Clinical outcomes improved
      for all subjects and improvements were sustained two months post-discharge from
      in-home telerehabilitation. The satisfaction of the participants with in-home
      telerehabilitation services was very high. The satisfaction of the health care
      professionals with the technology and the communication experience during the
      therapy sessions was similar or slightly lower. In conclusion, telerehabilitation
      for post-knee arthroplasty is a realistic alternative for dispensing
      rehabilitation services for patients discharged from an acute care hospital. 

PMID- 25945159
TI  - Wheelchair Seating Assessment and Intervention: A Comparison Between
      Telerehabilitation and Face-to-Face Service.
AB  - This study compared outcomes of wheelchair seating and positioning interventions
      provided by telerehabilitation (n=10) and face-to-face (n=20; 10 in each of two
      comparison groups, one urban and one rural). Comparison clients were matched to
      the telerehabilitation clients in age, diagnosis, and type of seating components
      received. Clients and referring therapists rated their satisfaction and
      identified if seating intervention goals were met. Clients recorded travel
      expenses incurred or saved, and all therapists recorded time spent providing
      service. Wait times and completion times were tracked. Clients seen by
      telerehabilitation had similar satisfaction ratings and were as likely to have
      their goals met as clients seen face-to-face; telerehabilitation clients saved
      travel costs. Rural referring therapists who used telerehabilitation spent more
      time in preparation and follow-up than the other groups. Clients assessed by
      telerehabilitation had shorter wait times for assessment than rural face-to-face
      clients, but their interventions took as long to complete. 

PMID- 25945160
TI  - A pilot telerehabilitation program: delivering early intervention services to
      rural families.
AB  - The enTECH Telerehabilitation Program explored the use of telerehabilitation as
      an alternative service delivery model for early intervention therapy services.
      Utilizing the Kentucky Telehealth Network, two families living in rural Kentucky
      received occupational therapy services over a 12-week period. Following program
      implementation, qualitative data was collected using participant journals and
      interviews. Data analysis identified three thematic categories related to the
      program: benefits/strengths, challenges/weaknesses, and recommendations for
      program improvement. Results of the program evaluation indicated that
      telerehabilitation has the potential to cost-effectively meet the therapeutic
      needs of children living in rural areas where provider shortages exist. The
      enTECH Telerehabilitation Program serves as a model for how telerehabilitation
      can be used to deliver early intervention services to ameliorate health
      disparities and improve access to rehabilitation services. 

PMID- 25945161
TI  - Methodology for analyzing and developing information management infrastructure to
      support telerehabilitation.
AB  - The proliferation of advanced technologies led researchers within the
      Rehabilitation Engineering Research Center on Telerehabilitation (RERC-TR) to
      devise an integrated infrastructure for clinical services using the University of
      Pittsburgh (PITT) model. This model describes five required characteristics for a
      telerehabilitation (TR) infrastructure: openness, extensibility, scalability,
      cost-effectiveness, and security. The infrastructure is to deliver clinical
      services over distance to improve access to health services for people living in
      underserved or remote areas. The methodological approach to design, develop, and
      employ this infrastructure is explained and detailed for the remote wheelchair
      prescription project, a research task within the RERC-TR. The availability of
      this specific clinical service and personnel outside of metropolitan areas is
      limited due to the lack of specialty expertise and access to resources. The
      infrastructure is used to deliver expertise in wheeled mobility and seating
      through teleconsultation to remote clinics, and has been successfully deployed to
      five rural clinics in Western Pennsylvania. 

PMID- 25945162
TI  - Telerehabilitation: policy issues and research tools.
AB  - The importance of public policy as a complementary framework for telehealth,
      telemedicine, and by association telerehabilitation, has been recognized by a
      number of experts. The purpose of this paper is to review literature on
      telerehabilitation (TR) policy and research methodology issues in order to report
      on the current state of the science and make recommendations about future
      research needs. An extensive literature search was implemented using search terms
      grouped into main topics of telerehabilitation, policy, population of users, and
      policy specific issues such as cost and reimbursement. The availability of
      rigorous and valid evidence-based cost studies emerged as a major challenge to
      the field. Existing cost studies provided evidence that telehomecare may be a
      promising application area for TR. Cost studies also indicated that
      telepsychiatry is a promising telepractice area. The literature did not reference
      the International Classification on Functioning, Disability and Health (ICF).
      Rigorous and comprehensive TR assessment and evaluation tools for outcome studies
      are tantamount to generating confidence among providers, payers, clinicians and
      end users. In order to evaluate consumer satisfaction and participation,
      assessment criteria must include medical, functional and quality of life items
      such as assistive technology and environmental factors. 

PMID- 25945163
TI  - Telerehabilitation clinical and vocational applications for assistive technology:
      research, opportunities, and challenges.
AB  - Rehabilitation service providers in rural or underserved areas are often
      challenged in meeting the needs of their complex patients due to limited
      resources in their geographical area. Recruitment and retention of the rural
      clinical workforce are beset by the ongoing problems associated with limited
      continuing education opportunities, professional isolation, and the challenges
      inherent in coordinating rural community healthcare. People with disabilities who
      live in rural communities also face challenges accessing healthcare. Traveling
      long distances to a specialty clinic for necessary expertise may be troublesome
      due to inadequate or unavailable transportation, disability specific limitations,
      and financial limitations. Distance and lack of access are just two threats to
      quality of care that now being addressed by the use of videoconferencing,
      information exchange, and other telecommunication technologies that facilitate
      telerehabilitation. This white paper illustrates and summarizes clinical and
      vocational applications of telerehabilitation. We provide definitions related to
      the fields of telemedicine, telehealth, and telerehabilitation, and consider the
      impetus for telerehabilitation. We review the telerehabilitation literature for
      assistive technology applications; pressure ulcer prevention; virtual reality
      applications; speech-language pathology applications; seating and wheeled
      mobility applications; vocational rehabilitation applications; and cost
      effectiveness. We then discuss external telerehabilitation influencers, such as
      the positions of professional organizations. Finally, we summarize clinical and
      policy issues in a limited context appropriate to the scope of this paper. 

PMID- 25945164
TI  - Telerehabilitation: State-of-the-Art from an Informatics Perspective.
AB  - Rehabilitation service providers in rural or underserved areas are often
      challenged in meeting the needs of their complex patients due to limited
      resources in their geographical area. Recruitment and retention of the rural
      clinical workforce are beset by the ongoing problems associated with limited
      continuing education opportunities, professional isolation, and the challenges
      inherent to coordinating rural community healthcare. People with disabilities who
      live in rural communities also face challenges accessing healthcare. Traveling
      long distances to a specialty clinic for necessary expertise is troublesome due
      to inadequate or unavailable transportation, disability specific limitations, and
      financial limitations. Distance and lack of access are just two threats to
      quality of care that now being addressed by the use of videoconferencing,
      information exchange, and other telecommunication technologies that facilitate
      telerehabilitation. This white paper illustrates and summarizes clinical and
      vocational applications of telerehabilitation. We provide definitions related to
      the fields of telemedicine, telehealth, and telerehabilitation, and consider the
      impetus for telerehabilitation. We review the telerehabilitation literature for
      assistive technology applications, pressure ulcer prevention, virtual reality
      applications, speech-language pathology applications, seating and wheeled
      mobility applications, vocational rehabilitation applications, and cost
      effectiveness. We then discuss external telerehabilitation influencers, such as
      the positions of professional organizations. Finally, we summarize clinical and
      policy issues in a limited context appropriate to the scope of this paper. 

PMID- 25945165
TI  - Telerehabilitation technologies: accessibility and usability.
AB  - In the fields of telehealth and telemedicine, phone and/or video technologies are
      key to the successful provision of services such as remote monitoring and visits.
      How do these technologies affect service accessibility, effectiveness, quality,
      and usefulness when applied to rehabilitation services in the field of
      telerehabilitation? To answer this question, we provide a overview of the complex
      network of available technologies and discuss how they link to rehabilitation
      applications, services, and practices as well as to the telerehabilitation end
      user. This white paper will first present the numerous professional
      considerations that shape the use of technology in telerehabilitation service and
      set it somewhat apart from telemedicine. It will then provide an overview of
      concepts essential to usability analysis; present a summary of various
      telerehabilitation technologies and their strengths and limitations, and consider
      how the technologies interface with end users' clinical needs for service
      accessibility, effectiveness, quality, and usefulness. The paper will highlight a
      conceptual framework (including task analyses and usability issues) that
      underlies a functional match between telerehabilitation technologies, clinical
      applications, and end-user capabilities for telerehabilitation purposes. Finally,
      we will discuss pragmatic issues related to user integration of
      telerehabilitation technology versus traditional face-to-face approaches. 

PMID- 25945166
TI  - Editor's Note: Volume Overview.

PMID- 25945167
TI  - Telecommunications and internet broadband policy: sorting out the pieces for
      telerehabilitation.
AB  - Technological change is accelerating and with it regulatory upheaval. Most of us
      agree that providing universal telecommunication services to all our citizens is
      a worthy ideal. Nonetheless, many of us do not agree that regulation should be
      the means to make broadband Internet services widely available. This Viewpoint
      begins sorting out pieces of the emerging United States, regulatory and policy
      puzzle for broadband Internet with an eye to the interests of telerehabilitation
      providers and consumers. Just how might changes in legal authority, regulation
      and agency jurisdictions impact us? 

PMID- 25945168
TI  - Telerehabilitation in Scotland: current initiatives and recommendations for
      future development.
AB  - Rehabilitation services are set to become central to modern health care systems
      as they strive to support an increasingly ageing population to live as
      independently as possible, while maintaining quality services. Alternative
      service delivery options such as telerehabilitation may assist in meeting the
      growing demand for services and many countries are exploring the potential use of
      telerehabilitation within their health care systems. The Scottish Centre for
      Telehealth commissioned an independent scoping study and subsequent report into
      the potential development and realisation of telerehabilitation services across
      Scotland. The scope of the report was restricted to adult rehabilitation services
      and aimed to identify opportunities for the use of telerehabilitation and to
      recommend clear and achievable steps toward implementation of telerehabilitation.
      This article outlines many of the telerehabilitation initiatives currently
      underway in Scotland and discusses some of the key recommendations made in the
      report to the Scottish Centre for Telehealth for the future advancement and
      application of telerehabilitation across Scotland. 

PMID- 25945169
TI  - Implementing telerehabilitation research for stroke rehabilitation with community
      dwelling veterans: lessons learned.
AB  - Telerehabilitation (TR) is the use of telehealth technologies to provide distant
      support, rehabilitation services, and information exchange between people with
      disabilities and their clinical providers. This article discusses the barriers
      experienced when implementing a TR multi-site randomized controlled trial for
      stroke patients in their homes, and the lessons learned. The barriers are divided
      into two sections: those specific to TR and those pertinent to the conduct of
      tele-research. The TR specific barriers included the rapidly changing
      telecommunications and health care environment and inconsistent equipment
      functionality. The barriers applicable to tele-research included the need to meet
      regulations in diverse departments and rapidly changing research regulations.
      Lessons learned included the need for: telehealth equipment options to allow for
      functionality within a diverse telecommunications infrastructure; rigorous pilot
      testing of all equipment in authentic situations; and on-call and on-site
      biomedical engineering and/or IT staff. 

PMID- 25945170
TI  - TeleSpeech Therapy Pilot Project: Stakeholder Satisfaction.
AB  - This pilot study of a school-based telepractice pilot project in a rural, remote
      county of North Carolina investigated the satisfaction of parents/caregivers,
      teachers, and administrators with a year-long telespeech therapy program
      delivered by a university clinic. Upon completion of the almost year-long
      project, a satisfaction survey incorporating a 5-point equal-appearing Likert
      scale (1= strongly disagree; 5= strongly agree) was disseminated to the
      stakeholders. The results were sorted by the three populations surveyed and
      indicated stakeholder satisfaction with student progress toward their speech and
      language goals, and clinician accessibility and responsiveness (mean ratings > 4
      points). The respondents (N=23) also indicated they would "recommend TeleSpeech
      Therapy to other school districts" (mean rating: 4.3). The only mean rating below
      4.0 was associated with teacher responses to the statement: "My expectations for
      the TeleSpeech Therapy program have been met" (mean rating: 3.92). Overall,
      parents/caregivers, teachers, and administrators appeared to find telepractice a
      satisfactory service delivery model for school-based speech-language therapy. 

PMID- 25945171
TI  - Editor's Note: Volume Overview.

PMID- 25945172
TI  - VOIP for Telerehabilitation: A Risk Analysis for Privacy, Security, and HIPAA
      Compliance.
AB  - Voice over the Internet Protocol (VoIP) systems such as Adobe ConnectNow, Skype,
      ooVoo, etc. may include the use of software applications for telerehabilitation
      (TR) therapy that can provide voice and video teleconferencing between patients
      and therapists. Privacy and security applications as well as HIPAA compliance
      within these protocols have been questioned by information technologists,
      providers of care and other health care entities. This paper develops a privacy
      and security checklist that can be used within a VoIP system to determine if it
      meets privacy and security procedures and whether it is HIPAA compliant. Based on
      this analysis, specific HIPAA criteria that therapists and health care facilities
      should follow are outlined and discussed, and therapists must weigh the risks and
      benefits when deciding to use VoIP software for TR. 

PMID- 25945173
TI  - A Role for YouTube in Telerehabilitation.
AB  - YouTube (http://youtube.com) is a free video sharing website that allows users to
      post and view videos. Although there are definite limitations in the
      applicability of this website to telerehabilitation, the YouTube technology
      offers potential uses that should not be overlooked. For example, some types of
      therapy, such as errorless learning therapy for certain language and cognitive
      deficits can be provided remotely via YouTube. In addition, the website's social
      networking capabilities, via the asynchronous posting of comments and videos in
      response to posted videos, enables individuals to gain valuable emotional support
      by communicating with others with similar health and rehabilitation challenges.
      This article addresses the benefits and limitations of YouTube in the context of
      telerehabilitation and reports patient feedback on errorless learning therapy for
      aphasia delivered via videos posted on YouTube. 

PMID- 25945174
TI  - Email intervention following traumatic brain injury: two case reports.
AB  - An email intervention for two individuals with TBI was conducted to investigate
      if this electronic medium shows potential as a therapeutic delivery method.
      Specifically, this study measured participants' compliance with a plan that
      incorporated email and a reading assignment. Prior to the email intervention, the
      clinician and participants designed an intervention plan which included specific
      guidelines for scheduled email correspondence regarding a daily reading task.
      After reviewing the daily emails, the clinician provided therapeutic feedback.
      The participants' compliance with the plan was measured by the punctuality of
      email correspondence and completion of tasks as detailed in the plan. Over a 4
      week intervention period, both participants demonstrated improvement in task
      completion and time adherence. Email proved to be a feasible option as a
      therapeutic delivery method for these individuals. 

PMID- 25945175
TI  - A blueprint for telerehabilitation guidelines.
AB  - Telerehabilitation refers to the delivery of rehabilitation services via
      information and communication technologies. Clinically, this term encompasses a
      range of rehabilitation and habilitation services that include assessment,
      monitoring, prevention, intervention, supervision, education, consultation, and
      counseling. Telerehabilitation has the capacity to provide service across the
      lifespan and across a continuum of care. Just as the services and providers of
      telerehabilitation are broad, so are the points of service, which may include
      health care settings, clinics, homes, schools, or community-based worksites. This
      document was developed collaboratively by members of the Telerehabilitation SIG
      of the American Telemedicine Association, with input and guidance from other
      practitioners in the field, strategic stakeholders, and ATA staff. Its purpose is
      to inform and assist practitioners in providing effective and safe services that
      are based on client needs, current empirical evidence, and available
      technologies. Telerehabilitation professionals, in conjunction with professional
      associations and other organizations are encouraged to use this document as a
      template for developing discipline-specific standards, guidelines, and practice
      requirements. 

PMID- 25945176
TI  - Editor's Note: Volume Overview.

PMID- 25945177
TI  - VOIP for Telerehabilitation: A Risk Analysis for Privacy, Security and HIPAA
      Compliance: Part II.
AB  - In a previous publication the authors developed a privacy and security checklist
      to evaluate Voice over Internet Protocol (VoIP) videoconferencing software used
      between patients and therapists to provide telerehabilitation (TR) therapy. In
      this paper, the privacy and security checklist that was previously developed is
      used to perform a risk analysis of the top ten VoIP videoconferencing software to
      determine if their policies provide answers to the privacy and security
      checklist. Sixty percent of the companies claimed they do not listen into video
      therapy calls unless maintenance is needed. Only 50% of the companies assessed
      use some form of encryption, and some did not specify what type of encryption was
      used. Seventy percent of the companies assessed did not specify any form of
      auditing on their servers. Statistically significant differences across company
      websites were found for sharing information outside of the country (p=0.010),
      encryption (p=0.006), and security evaluation (p=0.005). Healthcare providers
      considering use of VoIP software for TR services may consider using this privacy
      and security checklist before deciding to incorporate a VoIP software system for
      TR. Other videoconferencing software that is specific for TR with strong
      encryption, good access controls, and hardware that meets privacy and security
      standards should be considered for use with TR. 

PMID- 25945178
TI  - Telerehabilitation in South Africa - is there a way forward?
AB  - South Africa, like the rest of sub-Saharan Africa, has a disproportionate burden
      of disease and a shortage of health professionals. Telemedicine has been
      identified as a possible way of overcoming part of the problem but telemedicine
      has not been widely adopted. In the public sector hospitals in South Africa which
      serve 82% of the population there are 2.5 physiotherapists and 2 occupational
      therapists per 100,000 people served. The extent of telerehabilitation in South
      Africa is unknown. A literature review of telerehabilitation found no papers from
      South Africa. A survey of the heads of university departments of physiotherapy,
      occupational therapy and speech and language pathology revealed limited knowledge
      of telerehabilitation. Telerehabilitation services are confined to follow-up of
      patients at some institutions by telephone, fax or email. There is need to raise
      awareness among therapists if telerehabilitation is to become a reality in South
      Africa. Future actions are outlined. 

PMID- 25945179
TI  - Telerehabilitation: an adjunct service delivery model for early intervention
      services.
AB  - Early Intervention (EI) services for children birth through two years of age are
      mandated by Part C of the Individuals with Disabilities Education Act (IDEA);
      however, personnel shortages, particularly in rural areas, limit access for
      children who qualify. Telerehabilitation has the potential to build capacity
      among caregivers and local providers as well as promote family-centered services
      through remote consultation. This article provides an overview of research
      related to telerehabilitation and early intervention services; discusses the
      feasibility of telerehabilitation within traditional EI service delivery models;
      examines telecommunications technology associated with telerehabilitation; and
      provides hypothetical case examples designed to illustrate potential applications
      of telerehabilitation in early intervention. 

PMID- 25945180
TI  - A pilot exploration of speech sound disorder intervention delivered by telehealth
      to school-age children.
AB  - This article describes a school-based telehealth service delivery model and
      reports outcomes made by school-age students with speech sound disorders in a
      rural Ohio school district. Speech therapy using computer-based speech sound
      intervention materials was provided either by live interactive videoconferencing
      (telehealth), or conventional side-by-side intervention. Progress was measured
      using pre- and post-intervention scores on the Goldman Fristoe Test of
      Articulation-2 (Goldman & Fristoe, 2002). Students in both service delivery
      models made significant improvements in speech sound production, with students in
      the telehealth condition demonstrating greater mastery of their Individual
      Education Plan (IEP) goals. Live interactive videoconferencing thus appears to be
      a viable method for delivering intervention for speech sound disorders to
      children in a rural, public school setting. 

PMID- 25945182
TI  - From the desk of the guest editor: volume overview.

PMID- 25945183
TI  - Simulated in-home teletreatment for anomia.
AB  - This pilot study explored the feasibility of in-home teletreatment for patients
      with post-stroke anomia. Three participants over 65 years of age suffering from
      post-stroke anomia were treated in this pre/post-intervention case study. They
      received 12 speech therapy teletreatments (two sessions/week for 6 weeks) aimed
      at improving confrontation naming skills. Half of the failed items from a set of
      120 preselected stimuli were trained during treatment (Block A-trained stimuli)
      while the other half served as controls (Block B-untrained stimuli). Variables
      measured were: 1) efficacy of treatment (performance on Block-A vs. Block B
      Stimuli), and 2) participants' satisfaction with teletreatment (using a French
      adaptation of the Telemedicine satisfaction questionnaire). All participants
      showed a clinically relevant improvement on confrontation naming of trained items
      and less improvement for untrained items. The researchers also obtained high
      satisfaction scores on the questionnaire (above 57/60). This pilot study supports
      the feasibility of speech therapy teletreatments applied to neurological language
      disorders. 

PMID- 25945184
TI  - The World Health Organization/World Bank's first World Report on Disability.
AB  - In June, 2011 at the United Nations (UN) in New York City, the World Health
      Organization (WHO) and the World Bank launched the first World Report on
      Disability. This short overview of the Report provides information about its
      purpose, development and content, intended audiences, and outcomes. Special
      attention is directed to the sections of the Report which address
      telerehabilitation and information and communication technology. 

PMID- 25945185
TI  - Telehealth regulatory and legal considerations: frequently asked questions.
AB  - As telehealth gains momentum as a service delivery model in the United States
      within the rehabilitation professions, regulatory and legal questions arise. This
      article examines the following questions: Is there a need to secure licenses in
      two states (i.e., where the practitioner resides, and where the client is
      located), before engaging in telehealth?Do state laws differ concerning if and
      how telehealth can occur?Do any states expressly disallow telehealth?Can services
      delivered through telehealth be billed the same way as services provided in
      person?If practitioners fulfill the requirements to maintain licensure (e.g.,
      continuing education obligations) in their state of residence, do they also need
      to fulfill the requirements to maintain licensure for the state in which the
      client resides?Will professional malpractice insurance cover services delivered
      through telehealth?Does a sole practitioner need to abide by HIPAA
      regulations?Responses to these questions are offered to raise awareness of the
      regulatory and legal implications associated with the use of a telehealth service
      delivery model within the professions of occupational therapy, physical therapy,
      speech-language pathology and audiology. 

PMID- 25945186
TI  - Technology that Touches Lives: Teleconsultation to Benefit Persons with Upper
      Limb Loss.
AB  - While over 1.5 million individuals are living with limb loss in the United States
      (Ziegler-Graham et al., 2008), only 10% of these individuals have a loss that
      affects an upper limb. Coincident with the relatively low incidence of upper limb
      loss, is a shortage of the community-based prosthetic rehabilitation experts that
      can help prosthetic users to more fully integrate their devices into their daily
      routines. This article describes how expert prosthetists and occupational
      therapists at Touch Bionics, a manufacturer of advanced upper limb prosthetic
      devices, employ Voice over the Internet Protocol (VoIP) videoconferencing
      software telehealth technologies to engage in remote consultation with users of
      prosthetic devices and/or their local practitioners. The Touch Bionics staff
      provide follow-up expertise to local prosthetists, occupational therapists, and
      other health professionals. Contrasted with prior telephone-based consultations,
      the video-enabled approach provides enhanced capabilities to benefit persons with
      upper limb loss. Currently, the opportunities for Touch Bionics occupational
      therapists to fully engage in patient-based services delivered through telehealth
      technologies are significantly reduced by their need to obtain and maintain
      professional licenses in multiple states. 

PMID- 25945187
TI  - Telehealth forging ahead: overcoming barriers in licensure to improve access to
      care for service members.
AB  - The telehealth initiatives of the Department of Defense (DoD) and Veterans'
      Health Administration (VHA) continue to test the limits of technology to provide
      the best care to our service members, veterans and their families. The DoD and
      VHA have credentialing systems in place to allow clinical practice between
      facilities. New legislation in the form of the Servicemembers' Telemedicine and E
      Health Portability (STEP) Act will potentially expand telehealth clinical
      services across state lines into the homes of our service members and veterans. 

PMID- 25945188
TI  - The time has come for speech-language pathology license portability!
AB  - Melissa Jakubowitz, M.A., CCC-SLP is Vice President of SLP Services at
      PresenceLearning. A speech-language pathologist with over 20 years of clinical
      and managerial experience, Ms. Jakubowitz is a Board Recognized Specialist in
      Child Language. With a diverse clinical background, Ms. Jakubowitz began her
      career working in the public schools and has also operated a successful, multi
      office private practice. She is a past Director of the Scottish Rite Institute
      for Childhood Language Disorders in Stockton, CA. She is also a past-president of
      the California Speech-Language-Hearing Association, which, with over 5, 000 SLP
      members, is one of the largest speech-language pathologist state associations in
      the country. Active in the American Speech-Language-Hearing Association (ASHA),
      Ms. Jakubowitz served as a Legislative Counselor for 12 years. 

PMID- 25945189
TI  - Resolving barriers to licensure portability for telerehabilitation professionals.

PMID- 25945190
TI  - Editors' note: volume overview.

PMID- 25945191
TI  - Model collaboration: university library system and rehabilitation research team
      to advance telepractice knowledge.
AB  - This Publisher's Report describes the collaboration between a university library
      system's scholarly communication and publishing office and a federally funded
      research team, the Rehabilitation Engineering Research Center (RERC) on
      Telerehabilitation. This novel interdisciplinary collaboration engages
      librarians, information technologists, publishing professionals, clinicians,
      policy experts, and engineers and has produced a new Open Access journal,
      International Journal of Telerehabilitation, and a developing, interactive web
      based product dedicated to disseminating information about telerehabilitation.
      Readership statistics are presented for March 1, 2011 - February 29, 2012. 

PMID- 25945192
TI  - In-home Telerehabilitation for Older Persons with Chronic Obstructive Pulmonary
      Disease: A Pilot Study.
AB  - The purpose of this pilot study was to investigate the efficacy of in-home
      telerehabilitation for people with Chronic Obstructive Pulmonary Disease (COPD).
      Three community-living elders with COPD were recruited in a rehabilitation
      outpatient group and by direct referrals from pneumologists with outpatients who
      have COPD. A pre/post-test design without a control group was used for this pilot
      study. Telerehabilitation sessions (15 sessions) were conducted by two trained
      physiotherapists from a service center to the patient's home. Locomotor function
      (walking performance) and quality of life were measured in person prior to and at
      the end of the treatment by an independent assessor. Clinical outcomes improved
      for all subjects except for locomotor function in the first participant. In-home
      telerehabilitation for people with COPD is a realistic alternative to dispense
      rehabilitation services for patients requiring physical therapy follow-up. 

PMID- 25945193
TI  - Evaluation of a telerehabilitation system for community-based rehabilitation.
AB  - The use of web-based portals, while increasing in popularity in the fields of
      medicine and research, are rarely reported on in community-based rehabilitation
      programs. A program within the Pennsylvania Office of Vocational Rehabilitation's
      Hiram G. Andrews Center, the Cognitive Skills Enhancement Program (CSEP), sought
      to enhance organization of program and participant information and communication
      between part- and full-time employees, supervisors and consultants. A
      telerehabilitation system was developed consisting of (1) a web-based portal to
      support a variety of clinical activities, and (2) the Versatile Integrated System
      for Telerehabilitation (VISYTER) video-conferencing system to support the
      collaboration and delivery of rehabilitation services remotely. This descriptive
      evaluation examines the usability of the telerehabilitation system incorporating
      both the portal and VISYTER. Telerehabilitation system users include CSEP staff
      members from three geographical locations and employed by two institutions. The
      IBM After-Scenario Questionnaire (ASQ) and Post-Study System Usability
      Questionnaire (PSSUQ), the Telehealth Usability Questionnaire (TUQ), and two
      demographic surveys were administered to gather both objective and subjective
      information. Results showed generally high levels of usability. Users commented
      that the telerehabilitation system improved communication, increased access to
      information, improved speed of completing tasks, and had an appealing interface.
      Areas where users would like to see improvements, including ease of
      accessing/editing documents and searching for information, are discussed. 

PMID- 25945194
TI  - VoIP for Telerehabilitation: A Pilot Usability Study for HIPAA Compliance.
AB  - Consumer-based, free Voice and video over the Internet Protocol (VoIP) software
      systems such as Skype and others are used by health care providers to deliver
      telerehabilitation and other health-related services to clients. Privacy and
      security applications as well as HIPAA compliance within these protocols have
      been questioned by practitioners, health information managers, and other
      healthcare entities. This pilot usability study examined whether four respondents
      who used the top three, free consumer-based, VoIP software systems perceived
      these VoIP technologies to be private, secure, and HIPAA compliant; most did not.
      While the pilot study limitations include the number of respondents and systems
      assessed, the protocol can be applied to future research and replicated for
      instructional purposes. Recommendations are provided for VoIP companies,
      providers, and clients/consumers. 

PMID- 25945195
TI  - Speech Therapy Telepractice for Vocal Cord Dysfunction (VCD): MaineCare
      (Medicaid) Cost Savings.
AB  - This Brief Communication represents an analysis of the cost savings to MaineCare
      (also referred to as Medicaid) directly attributable to service provided via
      speech therapy telepractice. Seven female (primarily adolescent) MaineCare
      patients consecutively referred to Waldo County General Hospital (WCGH) with
      suspected diagnosis of Vocal Cord Dysfunction (VCD) were treated by speech
      therapy telepractice. Outcome data demonstrated a first month cost savings of
      $2376.72. The analysis additionally projected thousands of dollars of potential
      savings each month in reduced medical costs for this patient group as a result of
      successful treatment via speech therapy telepractice. The study suggests that
      without access to speech therapy telepractice for patients with VCD, the medical
      costs to MaineCare will be ongoing and significant. 

PMID- 25945196
TI  - Tele-Dysphagia management: an opportunity for prevention, cost-savings and
      advanced training.
AB  - Many patients survive severe stroke because of aggressive management in intensive
      care units. However, acquiring pneumonia during the post-onset phase
      significantly reduces both the quality and likelihood of survival. Aspiration
      pneumonia (AP), a relatively recent addition to the list of the pneumonias, is
      associated with dysphagia, a swallowing disorder that may cause aspiration of
      swallowed food or liquids mixed with bacterial pathogens common to saliva, or by
      aspiration of gastric contents due to emesis or gastroesophageal reflux. While it
      is within the purview of speech-language pathologists to provide evaluation,
      treatment, and management of dysphagia, the number of patients with dysphagia is
      growing faster than the number of qualified dysphagia clinicians. Because
      dysphagia consultations via telepractice are feasible and relatively accessible
      from a technological standpoint, they offer a promising strategy to bring the
      expertise of distant dysphagia experts to patients in underserved areas. Tele
      dysphagia management has the potential to increase patients' survival, enhance
      the expertise of primary, local clinicians, and reduce healthcare costs. Even a
      modest reduction in either hospital admissions for aspiration pneumonia, or in
      the length of stay for AP, could save the US health care system hundreds of
      millions of dollars each year. Wide spread tele-dysphagia management offers
      significant opportunities for prevention, cost-savings and advanced training, and
      is therefore worthy of consideration by stakeholders in the health care system
      and university training programs. 

PMID- 25945197
TI  - Making the case for uniformity in professional state licensure requirements.
AB  - Telehealth, the use of communication and information technologies to deliver
      health services, was initially envisioned as a way for persons in rural or remote
      settings to receive otherwise unavailable healthcare services. Now, in addition
      to overcoming personnel shortages for underserved populations, telehealth shows
      promise in meeting the needs of a constantly mobile U.S. society and workforce.
      Fortunately, telerehabilitation can meet the needs of a mobile society and
      workforce by enabling continuity of care for individuals who are out-of-town, on
      vacation, in temporary residence as a university student, or on business travel.
      Unfortunately, outdated legislative and regulatory policies and inhospitable
      infrastructures currently stand in the way of a seamless continuum of care. In
      2010, the American Telemedicine Association's Telerehabilitation Special Interest
      Group (TR SIG) convened a License Portability Sub-Committee to explore ways to
      diminish barriers for state licensure portability with a particular focus on
      physical therapy, occupational therapy, speech therapy, and audiology. In 2011,
      the Subcommittee published a factsheet (1) that detailed the challenges and
      potential solutions that surround the difficult issue of licensure portability.
      Concurrently, the American Telemedicine Association is advocating for national
      reform of professional licensure. (2) At the heart of all licensure requirements
      is the ability to determine who should be granted the authority to practice in a
      particular profession. This is done by focusing on educational, examination and
      behavioral requirements that are deemed the minimum necessary to protect the
      public from harm. States, however, with whom authority for licensure of health
      professionals rests, have independently defined those minimum requirements. This
      approach has led to a myriad of requirements that vary from state to state.
      Licensure portability will best succeed when variability between licensure
      requirements is minimized and an efficient licensure process exists. In this
      paper, these two critical factors for licensure portability are referred to as
      "licensure requirements" and "the credentialing process." Currently the
      variability between both of these factors is different between professions as
      well as between jurisdictions. To find the best solution to licensure
      portability, it is critical to determine which of these two elements create
      significant barriers for licensure mobility. This document outlines a method for
      the professions to begin collecting data to pinpoint the areas where agreement
      and variations exist in licensure requirements and processes between states. Such
      information will inform efforts towards uniformity. 

PMID- 25945198
TI  - Editors' note: volume overview.

PMID- 25945199
TI  - Lessons learned in pilot testing specialty consultations to benefit individuals
      with lower limb loss.
AB  - Telerehabilitation technologies enable the delivery of rehabilitation services
      from providers to people with disabilities as well as specialty care
      consultations. This article discusses the barriers experienced when planning and
      pilot testing a telerehabilitation multi-site specialty consultation for
      specialists in their medical centers, and the lessons learned. The barriers
      included integration and participation, coordination across organizational units,
      and privacy and information security. Lessons learned included the need for
      collaboration across multiple departments, telerehabilitation equipment back-ups,
      and anonymous and private communication protocols. Despite delays resulting from
      coordination at multiple levels of a national organization, we developed a
      program plan and successfully implemented a pilot test of the southeast region
      program. Specialty consultation using telerehabilitation delivery methods
      requires identifying provider preferences for technological features. Lessons
      learned could inform development of outpatient telerehabilitation for patients
      with amputations and studies of patients and providers involved in
      telerehabilitation. 

PMID- 25945201
TI  - Promising practices in e-supervision: exploring graduate speech-language
      pathology interns' perceptions.
AB  - E-supervision has a potential role in addressing speech-language personnel
      shortages in rural and difficult to staff school districts. The purposes of this
      article are twofold: to determine how e-supervision might support graduate speech
      language pathologist (SLP) interns placed in rural, remote, and difficult to
      staff public school districts; and, to investigate interns' perceptions of in
      person supervision compared to e-supervision. The study used a mixed methodology
      approach and collected data from surveys, supervision documents and records, and
      interviews. The results showed the use of e-supervision allowed graduate SLP
      interns to be adequately supervised across a variety of clients and professional
      activities in a manner that was similar to in-person supervision. Further, e
      supervision was perceived as a more convenient and less stressful supervision
      format when compared to in-person supervision. Other findings are discussed and
      implications and limitations provided. 

PMID- 25945200
TI  - The Multi-faceted Implementation of Telepractice to Service Individuals with
      Autism.
AB  - Telepractice is a method of service delivery in which professionals provide
      intervention, assessment and consultation services to individuals through the use
      of telecommunication technologies. In response to the nationwide school-based
      shortage of speech-language pathologists, telepractice has emerged as a viable
      way to reach underserved clients. Telepractice has the potential to extend to
      populations in need of services, including those diagnosed with autism. This
      paper examines an evidence-based clinical model for the delivery of telepractice
      services and describes the policies and procedures required for assessing
      individual need, confidentiality, technology, training and documentation within a
      telepractice program. Two clinical case studies involving individuals diagnosed
      with autism are described and provide initial evidence for the use of
      telepractice as a practical method for direct and consultative service delivery.
      Results indicated that both the student receiving direct services, and the
      treating clinician receiving consultative services via telepractice, demonstrated
      an increased skill level in target domains. 

PMID- 25945202
TI  - Overview of States' Use of Telehealth for the Delivery of Early Intervention
      (IDEA Part C) Services.
AB  - BACKGROUND: Early intervention (EI) services are designed to promote the
      development of skills and enhance the quality of life of infants and toddlers who
      have been identified as having a disability or developmental delay, enhance
      capacity of families to care for their child with special needs, reduce future
      educational costs, and promote independent living (NECTAC, 2011). EI services are
      regulated by Part C of the Individuals with Disabilities Education Improvement
      Act (IDEA); however, personnel shortages, particularly in rural areas, limit
      access for children who qualify. Telehealth is an emerging delivery model
      demonstrating potential to deliver EI services effectively and efficiently,
      thereby improving access and ameliorating the impact of provider shortages in
      underserved areas. The use of a telehealth delivery model facilitates inter
      disciplinary collaboration, coordinated care, and consultation with specialists
      not available within a local community. METHOD: A survey sent by the National
      Early Childhood Technical Assistance Center (NECTAC) to IDEA Part C coordinators
      assessed their utilization of telehealth within states' IDEA Part C programs.
      Reimbursement for provider type and services and barriers to implement a
      telehealth service delivery model were identified. RESULTS: Representatives from
      26 states and one jurisdiction responded to the NECTAC telehealth survey. Of
      these, 30% (n=9) indicated that they are either currently using telehealth as an
      adjunct service delivery model (n=6) or plan to incorporate telehealth within the
      next 1-2 years (n=3). Identified telehealth providers included developmental
      specialists, teachers of the Deaf/Hard of Hearing (DHH), speech-language
      pathologists, occupational therapists, physical therapists, behavior specialists,
      audiologists, and interpreters. Reimbursement was variable and included use of
      IDEA Part C funding, Medicaid, and private insurance. Expressed barriers and
      concerns for the implementation of telehealth as a delivery model within Part C
      programming included security issues (40%; n=11); privacy issues (44%; n=12);
      concerns about quality of services delivered via telehealth (40%; n=11); and lack
      of evidence to support the effectiveness of a telehealth service delivery model
      within IDEA Part C programming (3%; n=1). Reimbursement policy and billing
      processes and technology infrastructure were also identified as barriers
      impacting the implementation of telehealth programming. CONCLUSIONS: Provider
      shortages impact the quantity and quality of services available for children with
      disabilities and developmental delay, particularly in rural areas. While many
      states are incorporating telehealth within their Early Intervention (IDEA Part C)
      services in order to improve access and overcome personnel shortages, barriers
      persist. Policy development, education of stakeholders, research, utilization of
      secure and private delivery platforms, and advocacy may facilitate more
      widespread adoption of telehealth within IDEA Part C programs across the country.

PMID- 25945203
TI  - Perspectives of speech-language pathologists on the use of telepractice in
      schools: the qualitative view.
AB  - Telepractice in speech-language pathology shows the potential to mitigate the
      current shortage of speech-language pathologists (SLPs) available to serve a
      growing number of persons with communication disorders. Since a majority of
      American Speech-Language-Hearing Association (ASHA) certified SLPs work in
      schools and the population of communicatively impaired clients in schools
      continues to grow, research into the use of telepractice in the educational
      setting is warranted. This article reports upon the perspectives of SLPs
      regarding the use of telepractice in school settings. In-depth qualitative
      interviews were conducted with five SLPs experienced in the delivery of
      telepractice. Four major themes emerged: barriers, benefits, reasons for
      acceptance and use of telepractice, and suggestions to resolve telepractice
      professional issues. 

PMID- 25945204
TI  - Perspectives of speech-language pathologists on the use of telepractice in
      schools: quantitative survey results.
AB  - This research surveyed 170 school-based speech-language pathologists (SLPs) in
      one northeastern state, with only 1.8% reporting telepractice use in school
      settings. These results were consistent with two ASHA surveys (2002; 2011) that
      reported limited use of telepractice for school-based speech-language pathology.
      In the present study, willingness to use telepractice was inversely related to
      age, perhaps because younger members of the profession are more accustomed to
      using technology. Overall, respondents were concerned about the validity of
      assessments administered via telepractice; whether clinicians can adequately
      establish rapport with clients via telepractice; and if therapy conducted via
      telepractice can be as effective as in-person speech-language therapy. Most
      respondents indicated the need to establish procedures and guidelines for school
      based telepractice programs. 

PMID- 25945205
TI  - Speech telepractice: installing a speech therapy upgrade for the 21st century.
AB  - Much of speech therapy involves the clinician guiding the therapeutic process
      (e.g., presenting stimuli and eliciting client responses). However, this Brief
      Communication describes a different approach to speech therapy delivery.
      Clinicians at Waldo County General Hospital (WCGH) use high definition audio and
      video to engage clients in telepractice using interactive web-based virtual
      environments. This technology enables clients and their clinicians to co-create
      salient treatment activities using authentic materials captured via digital
      cameras, video and/or curricular materials. Both therapists and clients
      manipulate the materials and interact online in real-time. The web-based
      technology engenders highly personalized and engaging activities, such that
      clients' interactions with these high interest tasks often continue well beyond
      the therapy sessions. 

PMID- 25945208
TI  - Editors' note: volume overview.

PMID- 25945206
TI  - Tele-AAC Resolution.
AB  - Approximately 1.3% of all people, or about 4 million Americans, cannot rely on
      their natural speech to meet their daily communication needs. Telepractice offers
      a potentially cost-effective service delivery mechanism to provide clinical AAC
      services at a distance to the benefit of underserved populations in the United
      States and worldwide. Tele-AAC is a unique cross-disciplinary clinical service
      delivery model that requires expertise in both telepractice and augmentative and
      alternative communication (AAC) systems. The Tele-AAC Working Group of the 2012
      ISAAC Research Symposium therefore drafted a resolution underscoring the
      importance of identifying and characterizing the unique opportunities and
      constraints of Tele-AAC in all aspects of service delivery. These include, but
      are not limited to: needs assessments; implementation planning; device/system
      procurement, set-up and training; quality assurance, client progress monitoring,
      and follow-up service delivery. Tele-AAC, like other telepractice applications,
      requires adherence to the ASHA Code of Ethics and other policy documents, and
      state, federal, and international laws, as well as a competent technological
      infrastructure. The Working Group recommends that institutions of higher
      education and professional organizations provide training in Tele-AAC service
      provision. In addition, research and development are needed to create validity
      measures across Tele-AAC practices (i.e., assessment, implementation, and
      consultation); determine the communication competence levels achieved by Tele-AAC
      users; discern stakeholders' perceptions of Tele-AAC services (e.g.,
      acceptability and viability); maximize Tele-AAC's capacity to engage multiple
      team members in AAC assessment and ongoing service; identify the limitations and
      barriers of Tele-AAC provision; and develop potential solutions. 

PMID- 25945209
TI  - Outcomes of Clinicians, Caregivers, Family Members and Adults with Spina Bifida
      Regarding Receptivity to use of the iMHere mHealth Solution to Promote Wellness.
AB  - The purpose of this study was to gather information regarding the receptivity of
      clinicians, caregivers and family members, and adults with spina bifida (SB) to
      the use of a mHealth application, iMobile Health and Rehabilitation (iMHere)
      system. Surveys were administered to end user groups in conjunction with a
      conference presentation at the Spina Bifida Association's 38th Annual Conference.
      The survey results were obtained from a total of 107 respondents. Likert scale
      and qualitative results are provided in consideration of future application of
      the iMHere system in clinical practice. The results of this survey indicate
      respondents were receptive and supportive with regard to adopting such a system
      for personal and professional use. Challenges likely to be encountered in the
      introduction of the iMHere system are also revealed and discussed. 

PMID- 25945210
TI  - Teaching self-management skills in persons with chronic lower limb swelling and
      limited mobility: evidence for usability of telerehabilitation.
AB  - The purpose of this study was to evaluate the usability of telerehabilitation as
      a method of teaching self-management for chronic swelling of the lower limbs in
      persons with limited mobility. An in-home telerehabilitation self-management
      education protocol for chronic swelling of the lower limbs, termed
      Telerehabilitation to Empower You to Manage and Prevent Swelling (TR-PUMPS), was
      implemented using the Versatile and Integrated System for Telerehabilitation
      (VISYTER) software platform. Participants (n=11) were 36-79 years old,
      predominately female (72.7%) and diagnosed with a variety of health conditions.
      Participants' perceived usability scores of the remote delivery of TR-PUMPS was
      high with a median score of 6.67 (range 4.90 - 7.00) on a Likert scale: 1=
      disagree to 7= agree. There was no correlation between participants' familiarity
      with information technology and their perception of telerehabilitation usability.
      These results support telerehabilitation as a viable method for teaching a home
      based, self-management protocol for chronic swelling. 

PMID- 25945211
TI  - Telepractice in the assessment and treatment of individuals with aphasia: a
      systematic review.
AB  - Telepractice involves the application of technology to deliver services over a
      geographical distance. Studies in which telepractice procedures were used in the
      assessment or treatment of individuals with aphasia were reviewed. Systematic
      searches identified 10 studies meeting inclusion criteria. These studies were
      evaluated in terms of the: (a) characteristics of the participants, (b)
      technology utilized (c), services delivered via telepractice, (d) research
      methodology, and (e) results and conclusions of the study. Telepractice was used
      by speech-language pathologists and allied health professionals to assist with
      the delivery of services to participants with aphasia by their caretakers or
      clinicians. The services delivered included appraisal, diagnostic assessments,
      interventions, and consultation. This review suggests that telepractice is a
      viable method of service delivery for individuals with aphasia, however further
      research is warranted. Guidelines for practitioners and potential directions for
      future research are discussed. 

PMID- 25945212
TI  - School-based telerehabilitation in occupational therapy: using telerehabilitation
      technologies to promote improvements in student performance.
AB  - This article discusses the use of telerehabilitation technologies in occupational
      therapy for school-based practice. Telerehabilitation, for the purpose of this
      program, included the implementation of occupational therapy services via two-way
      interactive videoconferencing technology. The subjects included in this pilot
      program were children, ages 6 to 11 years, who attended an online charter school
      and had difficulties in the areas of fine motor and/or visual motor skills which
      impacted success with handwriting. Each participant completed a virtual
      evaluation and six 30-minute intervention sessions. The Print ToolTM Assessment
      was used to determine progress pre- and post-program. A learning coach/student
      satisfaction survey was given at the end of the program to determine participant
      satisfaction. Outcomes revealed improvements in handwriting performance for most
      students who participated in the program and high satisfaction rates reported by
      all participants. 

PMID- 25945213
TI  - Measuring Costs and Outcomes of Tele-Intervention When Serving Families of
      Children who are Deaf/Hard-of-Hearing.
AB  - BACKGROUND: Optimal outcomes for children who are deaf/hard-of-hearing (DHH)
      depend on access to high quality, specialized early intervention services. Tele
      intervention (TI), the delivery of early intervention services via telehealth
      technology, has the potential to meet this need in a cost-effective manner.
      METHOD: Twenty-seven families of infants and toddlers with varying degrees of
      hearing loss participated in a randomized study, receiving their services
      primarily through TI or via traditional in-person home visits. Pre- and post-test
      measures of child outcomes, family and provider satisfaction, and costs were
      collected. RESULTS: The TI group scored statistically significantly higher on the
      expressive language measure than the in-person group (p =.03). A measure of home
      visit quality revealed that the TI group scored statistically significantly
      better on the Parent Engagement subscale of the Home Visit Rating Scales-Adapted
      & Extended (HOVRS-A+; Roggman et al., 2012). Cost savings associated with
      providing services via TI increased as the intensity of service delivery
      increased. Although most providers and families were positive about TI, there was
      great variability in their perceptions. CONCLUSIONS: Tele-intervention is a
      promising cost-effective method for delivering high quality early intervention
      services to families of children who are DHH.

PMID- 25945214
TI  - A Telephone-based Physiotherapy Intervention for Patients with Osteoarthritis of
      the Knee.
AB  - This study assessed the effects of a 6-week telephone based intervention on the
      pain intensity and physical function of patients with knee osteoarthritis (OA),
      and compared the results to physiotherapy conducted in the clinic. Fifty randomly
      selected patients with knee OA were assigned to one of two treatment groups: a
      clinic group (CG) and a tele-physiotherapy group (TG). The CG received thrice
      weekly physiotherapist administered osteoarthritis-specific exercises in the
      clinic for six weeks. The TG received structured telephone calls thrice-weekly at
      home, to monitor self-administered osteoarthritis-specific exercises.
      Participants' pain intensity and physical function were assessed at baseline,
      two, four, and six weeks, in the clinic environment. Within group comparison
      showed significant improvements across baseline, and at weeks two, four, and six
      for both TG and CG's pain intensity and physical function. Between-group
      comparison of CG and TG's pain intensity and physical function at baseline and
      weeks two, four, and six showed no significant differences. This study
      demonstrated that a six-week course of structured telephone calls thrice-weekly
      to patients at their home, to monitor self-administered osteoarthritis-specific
      exercises for patients with knee OA (i.e., tele-physiotherapy) achieved
      comparable results to physiotherapy conducted in the clinic. 

PMID- 25945215
TI  - The Use of E-supervision to Support Speech-Language Pathology Graduate Students
      during Student Teaching Practica.
AB  - In the present feasibility study, e-supervision was used to provide university
      liaison supervision to speech-language pathology (SLP) graduate students enrolled
      in student teaching practica. Utilizing a mixed methodology approach, interview
      and survey data were compared in order to identify similarities and differences
      between in-person and e-supervision, and guide future practice. Results showed e
      supervised graduate students perceived that they received adequate supervision,
      feedback, support, and communication. Further, e-supervision provided additional
      benefits to supervisors, children on the caseload, and universities. Despite the
      benefits, disadvantages emerged. Implications for future practice and limitations
      of the study were identified. 

PMID- 25945216
TI  - Editors' note: volume overview.
AB  - The spring 2014 issue of the International Journal of Telerehabilitation (IJT)
      contains four informative and timely policy articles: (1) an invited commentary
      describing the exploratory process underway within physical therapy to create
      licensure portability for physical therapists, (2) an analysis of state
      telehealth laws and regulations for occupational therapy and physical therapy,
      (3) an overview of telehealth evidence and key telehealth policy issues in
      occupational therapy, and (4) the World Federation of Occupational Therapists'
      (WFOT) Position Statement on Telehealth. This issue also contains original
      research evaluating the feasibility of providing pediatric dysphagia treatment
      via telepractice, a clinical report of student learning outcomes associated with
      an innovative experiential learning assignment involving (international)
      teleconsultation in a Master of Science in Occupational Therapy (MSOT)
      curriculum, a book review, and announcements from the American Telemedicine
      Association. 

PMID- 25945217
TI  - Telepractice for pediatric Dysphagia: a case study.
AB  - A closed-ended intensive pediatric swallowing telepractice program was developed
      and piloted in one pediatric patient with Opitz BBB/G and Asperger's Syndromes,
      oropharyngeal dysphagia and aerophagia. The present study is a case report.
      Outcome variables included behavioral, swallowing and quality of life variables,
      and were assessed at baseline and at the end of the four-week program. Selective
      variables were also assessed at a follow-up family interview four weeks post
      program completion. Over the four-week intervention period, the patient
      demonstrated substantial improvements in: oral acceptance of eating-related
      objects and a variety of foods (behavioral variable), timing of voluntary saliva
      swallows and aerophagia levels (swallowing variables) and quality of life. Follow
      up interview analysis showed that most skills were retained or improved one-month
      post intervention. This intensive telepractice program proved to be feasible and
      effective for this pediatric patient with dysphagia. 

PMID- 25945218
TI  - An analysis of state telehealth laws and regulations for occupational therapy and
      physical therapy.
AB  - This study conducted a scan of telehealth occupational therapy and physical
      therapy state laws and regulations. The laws and regulations were analyzed to
      determine the potential effect they could have on occupational therapists' and
      physical therapists' utilization of telehealth. The results indicate that the
      majority of occupational therapy and physical therapy boards are silent on
      telehealth. A handful of physical therapy laws and regulations address
      "consultation by means of telecommunication," but do not provide any guidance for
      practitioners seeking to provide direct telehealth-delivered services to
      patients. Of the few states that do provide guidance, policy had the potential to
      provide clarity or inhibit adoption. The findings suggest that as state boards
      consider crafting telehealth regulations, they should do so in a manner that
      facilitates, rather than hampers adoption, while upholding their providers to a
      high standard of care. 

PMID- 25945219
TI  - Licensure portability: assuring access to quality care in physical therapy.
AB  - The concurrent circumstances of an increasingly mobile workforce, disparities in
      access to healthcare, and the ability to deliver care through technology (e.g.,
      telehealth) present the need and the opportunity for practice across state
      borders. Over the past four years, the Federation of State Boards of Physical
      Therapy (FSBPT) has explored professional licensure models that will allow cross
      border practice. This paper reviews FSBPT's exploratory process and describes
      some of the advantages of an interstate compact. It concludes that if agreement
      among state licensing boards can be achieved, a compact could serve as a viable
      means to increase patient access to quality physical therapy care. 

PMID- 25945220
TI  - Telehealth: a rapidly developing service delivery model for occupational therapy.
AB  - Over the past decade, the practice of occupational therapy has been increasingly
      influenced by technological advances in the use of information and communication
      technologies (ICT) and associated changes in health care policy. Emergent from
      this evolution is the application of telehealth to deliver occupational therapy
      services to a client who is in a different physical location than the provider.
      This article furnishes an overview of the evidence for telehealth use in
      occupational therapy, discusses key policy considerations, and provides resources
      to guide practitioners in the ethical use of telehealth. 

PMID- 25945221
TI  - World Federation of occupational therapists' position statement on telehealth.
AB  - The purpose of this document is to state the World Federation of Occupational
      Therapists' (WFOT) position on the use of telehealth for the delivery of
      occupational therapy services. Telehealth is the use of information and
      communication technologies (ICT) to deliver health-related services when the
      provider and client are in different physical locations. Additional terms used to
      describe this service delivery model include: tele-occupational therapy,
      telerehabilitation, teletherapy, telecare, telemedicine, and telepractice, among
      other terms. Telehealth may be used by occupational therapy practitioners for
      evaluation, intervention, monitoring, supervision, and consultation (between
      remote therapist, client, and/or local health-care provider) as permitted by
      jurisdictional, institutional, and professional regulations and policies
      governing the practice of occupational therapy. Occupational therapy services via
      telehealth should be appropriate to the individuals, groups and cultures served,
      and contextualized to the occupations and interests of clients. Important
      considerations related to licensure/registration, collaboration with local
      occupational therapists, client selection, consent to treat, professional
      liability insurance, confidentiality, personal and cultural attributes, provider
      competence/standards of care, reimbursement/payer guidelines, and authentic
      occupational therapy practice are discussed. 

PMID- 25945222
TI  - Teleconsultation with a developing country: student reported outcomes of
      learning.
AB  - This qualitative study explored the benefits of implementing (international)
      teleconsultation in a Master of Science in Occupational Therapy (MSOT)
      curriculum. Twenty-one students provided supervised teleconsultative services to
      individuals with disabilities in Guatemala and were responsible for completing
      assessments, setting goals, and providing resources to address goals and improve
      quality of life. Data were collected through student presentations and coded for
      relevant themes. Analysis revealed new learning in the areas of the occupational
      therapy process, cultural awareness, and technology. Three themes emerged:
      Increased Understanding of Awareness of and Challenges to Working with People of
      a Different Culture; Need for Adaptability and Flexibility as Practicing
      Clinicians; Emerging Role of Technology in Occupational Therapy. Based on results
      from this study, occupational therapy academicians should consider implementing
      similar programs into curricula and conduct related research in order to promote
      not only student learning, but also to advance the use of telehealth technology
      in occupational therapy practice. 

PMID- 25945224
TI  - Editors' note.
AB  - The Fall 2014 issue of the International Journal of Telerehabilitation (IJT)
      contains original research that evaluates the role of teletherapy and online
      language exercises in the treatment of chronic aphasia; investigates whether
      improvements are maintained after in-home pulmonary telerehabilitation for
      patients with chronic obstructive pulmonary disease; and studies the use of in
      home telerehabilitation for proximal humerus fractures. Within the context of two
      case studies, authors evaluated three service delivery models (direct, hybrid,
      and telepractice) for stuttering intervention. The results of a preliminary
      qualitative investigation are presented for telepractice in rural schools in
      Australia. And, schemas are offered for privacy and security analyses for store
      and forward applications in physical and occupational therapy. The Fall 2014
      issue also contains a book review, and announcements from the American
      Telemedicine Association and the Mid-Atlantic Telehealth Resource Center. 

PMID- 25945225
TI  - Combining Teletherapy and On-line Language Exercises in the Treatment of Chronic
      Aphasia: An Outcome Study.
AB  - We report a 12-week outcome study in which nine persons with long-term chronic
      aphasia received individual and group speech-language teletherapy services, and
      also used on-line language exercises to practice from home between therapy
      sessions. Participants were assessed at study initiation and completion using the
      Western Aphasia Battery, a portion of the Communicative Effectiveness Index, ASHA
      National Outcome Measurement System, and RIC Communication Confidence Rating
      Scale for Aphasia; additionally participants were polled regarding satisfaction
      at discharge. Pretreatment and post-treatment means were calculated and compared,
      and matched t-tests were used to determine significance of improvements following
      treatment, with patterns of independent on-line activity analyzed. Analysis of
      scores shows that means improved on most measures following treatment, generally
      significantly: the WAB AQ improved +3.5 (p = .057); the CETI Overall (of items
      administered) - +17.8 (p = .01), and CCRSA Overall - + 10.4 (p = .0004).
      Independent work increased with time, and user satisfaction following
      participation was high. 

PMID- 25945226
TI  - Are improvements maintained after in-home pulmonary telerehabilitation for
      patients with chronic obstructive pulmonary disease?
AB  - This study investigated if improvements can be maintained over 24 weeks when in
      home pulmonary telerehabilitation is combined with asynchronous self-management
      education for Chronic Obstructive Pulmonary Disease (COPD). Twenty-three
      community-living elders with moderate to very severe COPD participated in a
      pre/post-intervention study. Over 8 weeks, they had access to self-learning
      capsules on self-management, received 15 in-home teletreatment sessions and were
      encouraged to gradually engage in unsupervised sessions. Participants were
      assessed before the intervention (T1), immediately after the intervention (T2),
      and 6 months later (T3). Outcome measures were (1) exercise tolerance (6-minute
      walk test [6MWT]), Cycle Endurance Test [CET]), and (2) quality of life (Chronic
      Respiratory Questionnaire [CRQ]). Although there were significant improvements
      after 8 weeks of pulmonary telerehabilitation on the 6MWT, CET and three of four
      CRQ domains, none of these improvements were maintained after 6 months and scores
      returned to their baseline values (all p values > 0.05 when comparing T3 with
      T1). While pulmonary telerehabilitation is possible and has a positive impact on
      patients with moderate to very severe COPD, improvements were not maintained in
      the long-term even when physical therapy was accompanied by self-management
      education. 

PMID- 25945227
TI  - In-home telerehabilitation for proximal humerus fractures: a pilot study.
AB  - The objective of this study was to investigate the feasibility of an in-home
      telerehabilitation program for proximal humerus fractures. Seventeen patients
      with proximal humerus fractures were recruited by an orthopedic specialist during
      emergency room visits. Telerehabilitation treatments were given at the patient's
      home over an 8-week period using a videoconferencing system. Pain (Short-Form
      McGill Pain Questionnaire [SF-MPQ]), disabilities including shoulder range of
      motion (flexion, extension, internal rotation, external rotation, abduction), and
      upper limb function (Disability of the Arm, Shoulder and Hand questionnaire
      [DASH]) were measured in face-to-face evaluations before (T1) and immediately
      after (T2) the program. Participant satisfaction with the health care received
      was also evaluated at T2 with the Health care satisfaction questionnaire. All the
      clinical outcomes improved post-intervention (p < 0.05). Also, patient
      satisfaction was high (overall score of 82 +/- 7%). Therefore, in-home
      teletreatment seems to be a promising way to dispense rehabilitation services for
      this population. 

PMID- 25945228
TI  - Satisfaction with Cognitive Rehabilitation Delivered via the Internet in Persons
      with Acquired Brain Injury.
AB  - We examined the level of satisfaction with cognitive rehabilitation delivered via
      the Internet in persons with moderate to severe acquired brain injury (ABI).
      Fifteen adults with moderate to severe ABI were randomized to 30 days of Internet
      based active treatment (AT) or to a wait list (WL) group, and crossed over to the
      opposite condition after 30 sessions. Both caregivers and participants were
      assessed at three time points during the study. This study focused on participant
      satisfaction with receiving treatment in this manner. Though the results of this
      study showed no significant treatment effect, the vast majority of participants
      (>87%) were satisfied with treatment. Treatment satisfaction accounted for 25% of
      additional variance in predicting lower family ratings of mood difficulties after
      final assessment (p<.03). Greater satisfaction with treatment was positively
      correlated with greater employment rate after treatment (r=.63, p=.02), as well
      as lower family ratings of memory and mood difficulties after final assessment
      (r=-.59, p=.03; r=-.58, p=.03,). Results suggest that treatment satisfaction in
      persons with ABI is related to less activity limitations, and maintaining
      employment after cognitive rehabilitation delivered via the Internet. 

PMID- 25945230
TI  - Multiple stakeholder perspectives on teletherapy delivery of speech pathology
      services in rural schools: a preliminary, qualitative investigation.
AB  - The objective of this study was to investigate stakeholders' views on the
      feasibility and acceptability of a pilot speech pathology teletherapy program for
      children attending schools in rural New South Wales, Australia. Nine children
      received speech pathology sessions delivered via Adobe Connect(r) web
      conferencing software. During semi-structured interviews, school principals (n =
      3), therapy facilitators (n = 7), and parents (n = 6) described factors that
      promoted or threatened the program's feasibility and acceptability. Themes were
      categorized according to whether they related to (a) the use of technology; (b)
      the school-based nature of the program; or (c) the combination of using
      technology with a school-based program. Despite frequent reports of difficulties
      with technology, teletherapy delivery of speech pathology services in schools was
      highly acceptable to stakeholders. However, the use of technology within a school
      environment increased the complexities of service delivery. Service providers
      should pay careful attention to planning processes and lines of communication in
      order to promote efficiency and acceptability of teletherapy programs. 

PMID- 25945229
TI  - Stuttering intervention in three service delivery models (direct, hybrid, and
      telepractice): two case studies.
AB  - This study assessed outcomes in stuttering intervention across three service
      delivery models: direct, hybrid, and telepractice for two 11-year old children
      who stutter. The goal of the study was to investigate whether short-term goals
      were maintained through the telepractice sessions. The Stuttering Severity
      Instrument, Fourth Edition (SSI-4) was administered to each child before and
      after each intervention period and weekly fluency samples (percentage of
      stuttered syllables in a monologue) were obtained in each of the 10-week
      intervention periods. In addition, the Communication Attitudes Test-Revised was
      used to assess the children's attitudes toward speaking. Following the
      telepractice period, parents and children completed a questionnaire concerning
      the therapy experience via telepractice. Both children continued to improve
      fluency as measured by the weekly fluency samples. SSI-4 severity ratings
      improved for one child and remained consistent for the other. These outcomes
      appear to demonstrate that telepractice is viable for improving and maintaining
      fluency. 

PMID- 25945231
TI  - Telerehabilitation store and forward applications: a review of applications and
      privacy considerations in physical and occupational therapy practice.
AB  - An overview of store and forward applications commonly used in physical and
      occupational therapy practice is reviewed with respect to regulation, privacy,
      security, and clinical applications. A privacy and security checklist provides a
      clear reference of pertinent regulatory issues regarding these software
      applications. A case study format is used to highlight clinical applications of
      store and forward software features. Important considerations of successful
      implementation of store and forward applications are also identified and
      discussed. 

PMID- 25945232
TI  - Intrauterine programming.
AB  - In mammals, the intrauterine condition has an important role in the development
      of fetal physiological systems in later life. Suboptimal maternal environment can
      alter the regulatory pathways that determine the normal development of the fetus
      in utero, which in post-natal life may render the individual more susceptible to
      cardiovascular or metabolic adult-life diseases. Changes in the intrauterine
      availability of nutrients, oxygen and hormones can change the fetal tissue
      developmental regulatory planning, which occurs genomically and non-genomically
      and can cause permanent structural and functional changes in the systems, leading
      to diseases in early years of life and those that particularly become overt in
      adulthood. In this review we take a brief look at the main elements which program
      the fetal system development and consequently induce a crucial impact on the
      cardiovascular, nervous and hormonal systems in adulthood. 

PMID- 25945233
TI  - Effects of Nigella sativa oil and ascorbic acid against oxytetracycline-induced
      hepato-renal toxicity in rabbits.
AB  - OBJECTIVES: Oxytetracycline (OTC) is a broad spectrum antibiotic widely used for
      treatment of a wide range of infections. However, its improper human and animal
      use leads to toxic effects, including hepatonephrotoxicity. Our objective was to
      evaluate protective effects of Nigella sativa oil (NSO) and/or ascorbic acid
      (AA), against OTC-induced hepatonephrotoxicity in rabbits. MATERIALS AND METHODS:
      Forty male white New Zealand rabbits were divided into 5 groups of eight each.
      The 1(st) group (control) was given saline. The 2(nd) group was given OTC (200
      mg/kg, orally). The 3(rd) and 4(th) groups were orally administered NSO and AA (2
      ml/kg and 200 mg/kg respectively) 1 hr before OTC administration at the same dose
      regimen used for the 2(nd) group. Both NSO and AA were given in combination for
      the 5(th) group along with OTC administration. Serum biochemical parameters
      related to liver and kidney injury were evaluated, and lipid peroxidation as well
      as antioxidant markers in hepatic and renal tissues were examined. RESULTS: OTC
      treated animals revealed significant alterations in serum biochemical hepato
      renal injury markers, and showed a markedly increase in hepato-renal lipid
      peroxidation and inhibition in tissue antioxidant biomarkers. NSO and AA protect
      against OTC-induced serum and tissue biochemical alterations when each of them is
      used alone or in combination along with OTC treatment. Furthermore, both NSO and
      AA produced synergetic hepatoprotective and antioxidant properties. CONCLUSION:
      The present study revealed the preventive role of NSO and/or AA against the toxic
      effects of OTC through their free radical-scavenging and potent antioxidant
      activities.

PMID- 25945234
TI  - Alpha-lipoic acid loaded in chitosan conduit enhances sciatic nerve regeneration
      in rat.
AB  - OBJECTIVES: To investigate the effect of topical administration of alpha-lipoic
      acid into chitosan conduit on peripheral nerve regeneration using a rat sciatic
      nerve transection model. MATERIALS AND METHODS: Forty five Wistar rats were
      divided into three experimental groups randomly. A 10-mm gap of sciatic nerve was
      bridged with a chitosan conduit following surgical preparation and anesthesia. In
      treatment group, the conduit was filled with 30 ul alpha-lipoic acid (10
      mg/kg/bw).It was filled with 30 ul phosphate buffered saline solution in control
      group. In Sham group sciatic nerve was just exposed. RESULTS: The recovery of
      nerve function was faster in treatment group than in control, at 4 and 8 weeks
      after surgery (P-value<0.05). Conduction velocity was better in treatment group
      than in control group at 4 and 12 weeks (P-value<0.05). Recovery index was higher
      in treatment group than the control group, 8 weeks after surgery (P-value <0.05).
      Greater nerve fiber diameter, axon diameter, and myelin sheath thickness were
      observed in treatment group compared to control group at 8 and 12 weeks after
      surgery (P-value<0.05). The immunoreactivity of regenerated axons and myelin
      sheath in treatment group were far more similar to sham group. CONCLUSION: Alpha
      lipoic acid when loaded in a chitosan conduit could improve transected sciatic
      nerve regeneration in rat.

PMID- 25945235
TI  - The spatial learning and memory performance in methamphetamine-sensitized and
      withdrawn rats.
AB  - OBJECTIVES: There is controversial evidence about the effect of methamphetamine
      (METH) on spatial memory. We tested the time- dependent effects of METH on
      spatial short-term (working) and long-term (reference) memory in METH -sensitized
      and withdrawn rats in the Morris water maze. MATERIALS AND METHODS: Rats were
      sensitized to METH (2 mg/kg, daily/5 days, SC). Rats were trained in water maze
      (4 trials/day/for 5 days). Probe test was performed 24 hr after training. Two
      days after probe test, working memory training (2 trials/day/for 5 days) was
      conducted. Acquisition-retention interval was 75 min. The treatment was continued
      per day 30 and 120 min before the test. Two groups of METH -sensitized rats were
      trained in reference memory after a longer period of withdrawal (30 days).
      RESULTS: Sensitized rats exhibited significantly longer escape latencies on the
      training, spent significantly less time in the target zone (all, P<0.05), and
      their working memory impaired 30 min after injection. While, METH has no effect
      on the spatial learning process 120 min after injection, and rats spent
      significantly less time in the target zone (P<0.05), as well it has no effect on
      working memory. Also, impairment of reference memory persisted after prolonged
      abstinence. CONCLUSION: Our findings indicated that METH impaired spatial
      learning and memory 30 min after injection, but spared spatial learning, either
      acquisition or retention of spatial working, but partially impaired retention of
      spatial reference memory following 120 min after injection in sensitized rats,
      which persisted even after prolonged abstinence.

PMID- 25945237
TI  - Immunotherapeutic effects of pentoxifylline in type 1 diabetic mice and its role
      in the response of T-helper lymphocytes.
AB  - OBJECTIVES: Pentoxifylline is an immunomodulatory and anti-inflammatory agent and
      is used in vascular disorders. It has been shown that pentoxifylline inhibits
      proinflammatory cytokines production. The purpose of this study was to
      investigate the therapeutic effects of pentoxifylline on the treatment of
      autoimmune diabetes in mice. MATERIALS AND METHODS: Diabetes was induced by
      multiple low dose of streptozotocin (MLDS) injection (40 mg/kg/day for 5
      consecutive days) in male C57BL/6 mice. After induction of diabetes, mice were
      treated with pentoxifylline (100 mg/kg/day IP) for 21 days. Blood glucose levels
      and plasma levels of insulin were measured. Splenocytes were tested for
      proliferation by MTT test and cytokine production by ELISA. RESULTS:
      Pentoxifylline treatment prevented hyperglycemia and increased plasma insulin
      levels in the diabetic mice. Aside from reducing lymphocyte proliferation,
      pentoxifylline significantly inhibited the production of proinflammatory
      interleukin 17 (IL-17) as well as interferon gamma (IFN-gamma), while increased
      anti-inflammatory cytokine IL-10 as compared with those in MLDS group (diabetic
      control group). CONCLUSION: These findings indicate that pentoxifylline may have
      therapeutic effect against the autoimmune destruction of the pancreatic beta
      cells during the development of MLDS-induced type 1 diabetes in mice.

PMID- 25945236
TI  - Acute and chronic effects of lithium on BDNF and GDNF mRNA and protein levels in
      rat primary neuronal, astroglial and neuroastroglia cultures.
AB  - OBJECTIVES: The neuroprotective effect of lithium has been attributed to its
      therapeutic action. However, the role of glial cells particularly astrocytes, and
      the possible interactions between neurons and astrocytes in neuroprotective
      effects of lithium have been disregarded. Thus, the aim of this study was to
      evaluate the direct effects of lithium on brain derived neurotrophic factor
      (BDNF) and glial cell line derived neurotrophic factor (GDNF) in rat primary
      neuronal, astrocytes, and mixed neuro-astroglial cultures to assess the possible
      effects of lithium on astrocytes and neuro-astroglia interactions. MATERIALS AND
      METHODS: Rat primary astrocyte, neuronal and mixed neuro-astrocyte cultures were
      prepared from cortices of 18-day embryos. Cell cultures were exposed to lithium
      (1 mM) or vehicle for 1 day (acute) or 7 days (chronic). BDNF and GDNF mRNA and
      protein levels were determined by RT-PCR and ELISA, respectively. RESULTS:
      Chronic but not acute lithium treatment increased intracellular BDNF and GDNF
      protein levels in rat primary neuronal and astrocyte cultures, respectively
      (P<0.05). However, chronic lithium treatment had no significant effect on
      intracellular BDNF protein level in astrocyte and mixed neuron-astrocyte cultures
      or GDNF protein levels in mixed neuron-astrocyte culture. Furthermore, acute and
      chronic lithium treatment had no significant effect on mRNA and extracellular
      BDNF and GDNF protein levels in three studied cultures. CONCLUSION: Present study
      showed that chronic lithium treatment affected neurotrophins both in neurons and
      astrocytes in a cell-type specific manner with no effect on neuron-astrocyte
      interactions. The findings of this study also highlighted the importance of
      astrocytes as drug targets involved in the neuroprotective action of lithium.

PMID- 25945238
TI  - Protective effects of vitamin B6 alone and in combination with L-cysteine and
      NaHS on ethanol and indomethacin-induced gastric lesions in mice.
AB  - OBJECTIVES: This study was undertaken to investigate the protective effects of
      vitamin B6, cofactor for cystathionine-gamma lyase and cystathionine-beta
      synthase (producers of H2S), alone and in combination with L-cysteine, H2S
      precursor, on indomethacin-, and ethanol-induced gastric lesions in male NMRI
      mice. MATERIALS AND METHODS: Fasted male NMRI mice were randomly assigned into 12
      groups (7 in each). The gastroprotective activity of vitamin B6 alone and in
      combination with L-cysteine and sodium hydrosulfate (NaHS) was evaluated against
      ethanol-, and indomethacin-induced gastric lesions. The animals were received
      vehicle, vitamin B6, L-cysteine, L-cysteine+vitamin B6, NaHS or NaHS+B6 before
      the induction of gastric lesions by ethanol (50%, 0.5 ml/25 g of body weight,
      orally) or indomethacin (40 mg/kg, orally). One and five hours after the
      administration of ethanol and indomethacin, respectively, the animals were
      sacrificed using anesthetics. The stomachs were removed, rinsed with normal
      saline and assessed for gastric wall mucus changes. RESULTS: Pretreatment with L
      cysteine, sodium hydrosulfate, and vitamin B6 significantly decreased the total
      area of gastric lesions (P<0.01). The mucus production in L-cysteine-, sodium
      hydrosulfate-, and vitamin B6-treated animals were significantly higher than in
      control rats P<0.05). The gastroprotective activity of L-cysteine and sodium
      hydrosulfate in combination with vitamin B6 were higher than when administered
      alone (P<0.05). CONCLUSION: The result of this survey showed that the protective
      activity of L-cysteine and sodium hydrosulfate enhances in the presence of
      vitamin B6.

PMID- 25945239
TI  - Differentiation of adipocytes and osteocytes from human adipose and placental
      mesenchymal stem cells.
AB  - OBJECTIVES: Mesenchymal stem cells (MSC) can be isolated from adult tissues such
      as adipose tissue and other sources. Among these sources, adipose tissue (because
      of easy access) and placenta (due to its immunomodulatory properties, in addition
      to other useful properties), have attracted more attention in terms of research.
      The isolation and comparison of MSC from these two sources provides a proper
      source for clinical experimentation. The aim of this study was to compare the
      characteristics of MSC isolated from human adipose tissue and placenta. MATERIALS
      AND METHODS: Adipose and placental MSC were isolated from the subcutaneous
      adipose tissues of 10 healthy women (25 to 40 years) and from a fresh term
      placenta (n= 1), respectively. Stem cells were characterized and compared by flow
      cytometry using CD29, CD31, CD34, CD44, CD45, CD105, CD166 and HLA-DR markers.
      Osteocytes and adipocytes were differentiated from isolated human mesenchymal
      stem cells (HMSC). RESULTS: Adipose and placenta-derived MSC exhibited the same
      morphological features. ADSC differentiated faster than placenta; however, both
      were differentiated, taking up to 21 days for osteocyte and 14 days for adipocyte
      differentiation. About 90% of PLC-MSC and ADSC were positive for CD29, CD44,
      CD105, and CD166; and negative for CD31, CD34, CD45, and HLA-DR. CONCLUSION: The
      two sources of stem cells showed similar surface markers, morphology and
      differentiation potential and because of their multipotency for differentiating
      to adipocytes and osteocytes, they can be applied as attractive sources of MSC
      for regenerative medicine.

PMID- 25945240
TI  - Investigation on metabolism of cisplatin resistant ovarian cancer using a genome
      scale metabolic model and microarray data.
AB  - OBJECTIVES: Many cancer cells show significant resistance to drugs that kill drug
      sensitive cancer cells and non-tumor cells and such resistance might be a
      consequence of the difference in metabolism. Therefore, studying the metabolism
      of drug resistant cancer cells and comparison with drug sensitive and normal cell
      lines is the objective of this research. MATERIAL AND METHODS: Metabolism of
      cisplatin resistant and sensitive A2780 epithelial ovarian cancer cells and
      normal ovarian epithelium has been studied using a generic human genome-scale
      metabolic model and transcription data. RESULT: The results demonstrate that the
      most different metabolisms belong to resistant and normal models, and the
      different reactions are involved in various metabolic pathways. However, large
      portion of distinct reactions are related to extracellular transport for three
      cell lines. Capability of metabolic models to secrete lactate was investigated to
      find the origin of Warburg effect. Computational results introduced SLC25A10
      gene, which encodes mitochondrial dicarboxylate transporter involved in
      exchanging of small metabolites across the mitochondrial membrane that may play
      key role in high growing capacity of sensitive and resistant cancer cells. The
      metabolic models were also used to find single and combinatorial targets that
      reduce the cancer cells growth. Effect of proposed target genes on growth and
      oxidative phosphorylation of normal cells were determined to estimate drug side
      effects. CONCLUSION: The deletion results showed that although the cisplatin did
      not cause resistant cancer cells death, but it shifts the cancer cells to a more
      vulnerable metabolism.

PMID- 25945241
TI  - Effect of trinitroglycerin therapy on serum zinc and copper levels and liver
      enzyme activities in BALB/c mice infected with Leishmania major MRHO/IR/75/ER.
AB  - OBJECTIVES: To evaluate the effect of trinitroglycerin (TNG) as nitric oxide
      donor agent on serum copper (Cu) and zinc (Zn) levels and liver enzymes in BALB/c
      mice infected with Leishmania major (L. major) MRHO/IR/75/ER. MATERIALS AND
      METHODS: Inbred female mice were divided into three groups: healthy group
      (uninfected naive mice), control group (infected with L. major), and test group
      (L. major infected mice treated with TNG). TNG (200 ug/ul) was inoculated
      subcutaneously into the mice of the test group. Serum Cu and Zn levels and liver
      enzymes activities were then evaluated by atomic absorption spectrophometer and
      colorimetric methods, respectively. RESULTS: Serum Cu levels were significantly
      higher in the test group than in the control and naive groups (P-value <0.05),
      while Zn levels were higher in the test group than in the control group with no
      significant difference. Serum glutamicoxaloacetic transaminase concentrations in
      the test group were significantly lower than those in other groups (P-value
      <0.05), while serum glutamate pyruvic transaminase concentrations were
      significantly higher in test compared with those in other groups (P-value <0.05).
      Moreover, alkaline phosphatase in the control and test groups were significantly
      lower than that in the naive group (P-value <0.05). CONCLUSION: TNG treatment
      increased Zn and Cu levels and thus increased resistance to Leishmania because of
      the role of Zn and Cu; therefore, TNG therapy will be useful for treating
      cutaneous leishmania. In addition, the decrease of serum glutamicoxaloacetic
      transaminase activity can be an index of therapeutic process of TNG.

PMID- 25945242
TI  - In vitro protection of human lymphocytes from toxic effects of chlorpyrifos by
      selenium-enriched medicines.
AB  - OBJECTIVES: Chlorpyrifos (CP) is a broad-spectrum organophosphorus pesticide used
      extensively in agricultural and domestic pest control, accounting for 50% of the
      global insecticidal use. In the present study, protective effects of two selenium
      enriched strong antioxidative medicines IMOD and Angipars were examined in human
      lymphocytes treated with CP in vitro. MATERIALS AND METHODS: Isolated lymphocytes
      were exposed to 12 ug/ml CP either alone or in combination with effective doses
      (ED50) of IMOD (0.2 ug/ml) and Angipars (1 ug/ml). After 3 days incubation, the
      viability and oxidative stress markers including cellular lipid peroxidation
      (LPO), myeloperoxidase (MPO), total thiol molecules (TTM), and total antioxidant
      power (TAP) were evaluated. Also, the levels of tumor necrosis factor-alpha (TNF
      alpha), as inflammatory index along with acetylcholinesterase (AChE) activity and
      cell apoptosis were assessed by flow cytometry. RESULTS: Results indicated that
      effective doses of IMOD and Angipars reduced CP-exposed lymphocyte mortality rate
      along with oxidative stress. Both agents restored CP-induced elevation of TNF
      alpha and protected the lymphocytes from CP-induced apoptosis and necrosis.
      CONCLUSION: Overall, results confirm that IMOD and Angipars reduce the toxic
      effects associated with CP through free radical scavenging and protection from
      apoptosis and necrosis.

PMID- 25945243
TI  - Nerve growth factor in human semen: Effect of nerve growth factor on the
      normozoospermic men during cryopreservation process.
AB  - OBJECTIVES: Although routinely applied in assisted reproductive technology, human
      sperm cryopreservation is not a completely successful procedure. Adverse effects
      of cryopreservation on the fertilization capacity, motility, morphology, and
      viability of spermatozoa have been proven; cryopreservation has also shown a role
      in sperm DNA fragmentation and infertility. The post-thaw survival of spermatozoa
      improved after addition of supplementation of antioxidant molecules to freezing
      media. Nerve growth factor (NGF) as one of the prosurvival substances has gained
      great attention in recent years. The aim of this study was the usage of NGF as
      prosurvival factor after cryopreservation process of human semen samples to
      assess the motility and viability of sperm, nitric oxide (NO) concentration, and
      DNA fragmentation in normozoospermic men. MATERIALS AND METHODS: Semen samples
      were collected from 25 normozoospermic men and were divided into fresh semen
      samples as control group, frozen-thawed semen samples without addition of
      exogenous NGF, and three groups of semen samples cryopreserved with addition of
      exogenous NGF (0.5, 1, and 5 ng/ml) in freezing medium. Viability was assessed by
      eosin-negrosin staining technique. Motility was evaluated with inverted
      microscope. NO concentration and apoptosis content were measured with flow
      cytometry. RESULTS: Results showed that exogenous NGF at 0.5 ng/ml could
      significantly (P-value <0.05) influence viability, motility, nitric oxide, and
      DNA fragmentation content. CONCLUSION: Exogenous NGF as cryoprotectant improved
      sperm viability and motility, increased intracellular NO concentration, and
      decreased apoptosis content in normal human spermatozoa.

PMID- 25945244
TI  - Aqueous extract of Zizyphus jujuba fruit attenuates glucose induced neurotoxicity
      in an in vitro model of diabetic neuropathy.
AB  - OBJECTIVES: The neuroprotective effect of fruit aqueous extract of Ziziphus
      jujuba Lam on glucose-induced neurotoxicity in PC12 cells as an appropriate in
      vitro model of diabetic neuropathy was investigated. MATERIALS AND METHODS: Cell
      viability was determined by the MTT assay. Cellular reactive oxygen species (ROS)
      generation was measured by DCFH-DA analysis. Cleaved caspase-3, a biochemical
      parameter of cellular apoptosis, was measured by western blot analysis. RESULTS:
      Our data showed that a 4-fold elevation in glucose levels within the medium
      significantly reduced cell viability, increased intracellular ROS and caspase-3
      activation in PC12 cells after 24 hr. Incubation of the high glucose medium cells
      with 300-MUg/ml Z. jujuba fruit (ZJF) extract decreased the high glucose-induced
      cell toxicity and prevented caspase-3 activation and excited ROS generation.
      CONCLUSION: Thus, we concluded that the aqueous extract of Z. jujuba protects
      against hyperglycaemia-induced cellular toxicity. This could be associated with
      the prevention of ROS generation and neural apoptosis. Moreover, the results
      suggest that the ZJF has a therapeutic potential to attenuate diabetes
      complications such as neuropathy.

PMID- 25945245
TI  - Efficacy of optimized in vitro predegeneration period on the cell count and
      purity of canine Schwann cell cultures.
AB  - OBJECTIVES: Predegeneration is a standard technique to obtain mitotically
      activated and enriched cultures of Schwann cells (SCs). This study, for the first
      time, evaluated the impact of various duration of predegeneration on cell yield
      and enrichment of SCs from dog peripheral nerve. MATERIALS AND METHODS: Dog sural
      nerves were subjected to 5, 10, 15 day-long in vitro predegeneration. The total
      cell yield and the purity of SCs were evaluated in each group on the first and
      seventh day after plating. RESULTS: The maximum and minimum numbers of cells were
      counted in 15 day-long predegene-ration and control groups which underwent no
      predegeneration. The 10 day-long in vitro predegeneration group with 80+/-0.5%
      SCs enrichment had the best purity after plating day and could maintain its
      purity with elapsing on cultures. CONCLUSION: 10 day-long predegeneration results
      in the higher cell number and the better and prolonged purity of SCs in culture.

PMID- 25717365
TI  - An object oriented implementation of the Yeadon human inertia model.
AB  - We present an open source software implementation of a popular mathematical
      method developed by M.R. Yeadon for calculating the body and segment inertia
      parameters of a human body. The software is written in a high level open source
      language and provides three interfaces for manipulating the data and the model: a
      Python API, a command-line user interface, and a graphical user interface. Thus
      the software can fit into various data processing pipelines and requires only
      simple geometrical measures as input. 

PMID- 25945247
TI  - Evaluating the tolerability and acceptability of an alcohol-based hand rub - real
      life experience with the WHO protocol.
AB  - BACKGROUND: Optimizing user satisfaction with alcohol-based hand rubs (ABHR) may
      be vital to enhance hand hygiene performance. This study tested the tolerability
      and acceptability of a new ABHR (EVO9; Ecolab) in healthcare workers under daily
      working conditions and evaluated the practicability of the corresponding WHO
      protocol. METHODS: We strictly applied the WHO single product ABHR evaluation
      protocol. A trained observer assessed hand skin conditions of healthy volunteers
      using at least 30 ml ABHR per day during their clinical work at baseline, day 3-5
      and one month (visit 1-3). Participants rated ABHR tolerability and acceptability
      at visit 2 and 3. Additionally, we registered study time for participants and
      study team. RESULTS: Among 46 volunteers, 76% were female; 37% nurses, 28%
      physicians. Skin was observer-rated "not" or "incidentally" dry in 64.4%, 77.8%,
      and 90.9% participants at visit 1, 2, and 3, respectively. EVO9 was scored >=5
      (progressive scale, 1-7) for appearance, intactness, moisture content, and
      sensation by 95.7%, 97.7%, 88.9%, and 97.8% participants at visit 3,
      respectively. All WHO benchmarks were exceeded except for "speed of drying" at
      visit 2, and "texture" at visit 2 and 3. Cumulative study time expenditure was 14
      days for the observer and four days for participants. CONCLUSIONS: EVO9 was well
      tolerated and accepted according to the WHO single ABHR evaluation protocol with
      the potential for improvement for stickiness. The WHO protocol is feasible but
      requires considerable time and logistics. It does not preclude bias, in this case
      especially due to the necessary switch to personal dispensers.

PMID- 25945248
TI  - HIV-associated neurocognitive disorders.
AB  - Currently, neuropsychological impairment among HIV+ patients on antiretroviral
      therapy leads to a reduction in the quality of life and it is an important
      challenge due to the high prevalence of HIV-associated neurocognitive disorders
      and its concomitant consequences in relation to morbidity and mortality-
      including those HIV+ patients with adequate immunological and virological status.
      The fact that the virus is established in CNS in the early stages and its
      persistence within the CNS can help us to understand HIV-related brain injury
      even when highly active antiretroviral therapy is effective. The rising interest
      in HIV associated neurocognitive disorders has let to development new diagnostic
      tools, improvement of the neuropsychological tests, and the use of new biomarkers
      and new neuroimaging techniques that can help the diagnosis. Standardization and
      homogenization of neurocognitive tests as well as normalizing and simplification
      of easily accessible tools that can identify patients with increased risk of
      cognitive impairment represent an urgent requirement. Future efforts should also
      focus on diagnostic keys and searching for useful strategies in order to decrease
      HIV neurotoxicity within the CNS. 

PMID- 25945250
TI  - High-intensity focused ultrasound for the treatment of fibroadenomata (HIFU-F)
      study.
AB  - BACKGROUND: Breast fibroadenomata (FAD) are the most common benign lesions in
      women. For palpable lesions, there are currently three standard treatment
      options: reassurance (with or without follow-up), vacuum-assisted mammotomy (VAM)
      or surgical excision. High-intensity focused ultrasound (HIFU) ablation has been
      used in the treatment of FAD. The drawback of HIFU is its prolonged treatment
      duration. The aim of this trial is to evaluate circumferential HIFU treatment for
      the effective ablation of FAD with a reduced treatment time. METHODS/DESIGN:
      Fifty patients (age >=18 years) will be recruited with symptomatic FAD, visible
      on ultrasound (US, grade U2 benign). In patients >=25 years, cytology or
      histology will be performed to confirm the diagnosis of a FAD. These patients
      will receive HIFU treatment using the US-guided Echopulse device (Theraclion
      Ltd., Malakoff, France) under local anaesthesia. An additional 50 patients will
      be recruited and contacted 6 months after discharge from the breast clinic. These
      patients will be offered an US scan to determine the change in size of their FAD.
      This natural change in size will be compared to the decrease in size after HIFU
      treatment. Secondary outcome measures include post-treatment complications,
      patient recorded outcome measures, mean treatment time and cost analysis. TRIAL
      REGISTRATION: Current Controlled Trials: ISRCTN76622747.

PMID- 25945249
TI  - Sluggish cognitive tempo and its neurocognitive, social and emotive correlates: a
      systematic review of the current literature.
AB  - OBJECTIVES: Since the elimination of items associated with Sluggish Cognitive
      Tempo (SCT) during the transition from DSM-III to DSM-IV from the diagnostic
      criteria of Attention-deficit Hyperactivity Disorder (ADHD), interest in SCT and
      its associated cognitive as well as emotional and social consequences is on the
      increase. The current review discusses recent findings on SCT in clinical as well
      as community based ADHD populations. The focus is further on clinical correlates
      of SCT in populations different from ADHD, SCT's genetic background, SCT's
      association with internalizing and other behavioral comorbidities, as well as
      SCT's association with social functioning and its treatment efficacy. METHOD: A
      systematic review of empirical studies on SCT in ADHD and other pathologies in
      PsycInfo, SocIndex, Web of Science and PubMed using the key terms "Sluggish
      Cognitive Tempo", "Cognitive Tempo", "Sluggish Tempo" was performed. Thirty-two
      out of 63 studies met inclusion criteria and are discussed in the current review.
      RESULTS/CONCLUSION: From the current literature, it can be concluded that SCT is
      a psychometrically valid construct with additive value in the clinical field of
      ADHD, oppositional defiant disorder (ODD), internalizing disorders and neuro
      rehabilitation. The taxonomy of SCT has been shown to be far from consistent
      across studies; however, the impact of SCT on individuals' functioning (e.g.,
      academic achievement, social interactions) seems remarkable. SCT has been shown
      to share some of the genes with ADHD, however, related most strongly to non
      shared environmental factors. Future research should focus on the identification
      of adequate SCT measurement to promote symptom tailored treatment and increase
      studies on SCT in populations different from ADHD.

PMID- 25945251
TI  - The Child Illness and Resilience Program (CHiRP): a study protocol of a stepped
      care intervention to improve the resilience and wellbeing of families living with
      childhood chronic illness.
AB  - BACKGROUND: Families of children living with chronic illness are more vulnerable
      to mental health problems, however this can be ameliorated by a family's
      resilience. The Child Illness and Resilience Program (CHiRP) will develop and
      evaluate a parent-focussed family intervention designed to increase the
      resilience and wellbeing of families living with childhood chronic illness.
      METHODS/DESIGN: The study will be conducted in an Australian regional paediatric
      hospital and will use a stepped care intervention that increases in intensity
      according to parental distress. All parents of children discharged from the
      hospital will receive a family resilience and wellbeing factsheet (Step 1).
      Parents of children attending selected outpatient clinics will receive a family
      resilience and wellbeing activity booklet (Step 2). Parents who receive the
      booklet and report psychological distress at three-month follow-up will be
      randomised to participate in a family resilience information support group or
      waitlist control (Step 3). The Step 3 control group will provide data to compare
      the relative effectiveness of the booklet intervention alone versus the booklet
      combined with the group intervention for distressed parents. These participants
      will then receive the information support group intervention. All parents in Step
      2 and 3 will complete baseline, post-intervention and six month follow up
      assessments. The primary outcomes of the study will be changes in scores between
      baseline and follow-up assessments on measures of constructs of family
      resilience, including parental wellbeing, family functioning, family beliefs and
      perceived social support. Qualitative feedback regarding the utility and
      acceptability of the different intervention components will also be collected.
      DISCUSSION: It is hypothesised that participation in the CHiRP intervention will
      be associated with positive changes in the key outcome measures. If effective,
      CHiRP will provide an opportunity for the health sector to deliver a standardised
      stepped care mental health promotion intervention to families living with
      childhood chronic illness. TRIAL REGISTRATION: Australian clinical Trials
      Registry ACTRN 12613000844741 Universal Trial Number (UTN): 1111-1142-8829.

PMID- 25945253
TI  - Health, health behaviors, and health dissimilarities predict divorce: results
      from the HUNT study.
AB  - BACKGROUND: Poor health and health behaviors are associated with divorce. This
      study investigates the degree to which six health indicators and health behaviors
      among husbands and wives are prospectively related to divorce, and whether
      spousal similarities in these factors are related to a reduced risk of marital
      dissolution. Theoretically, a reduced risk is possible, because spousal
      similarity can help the couple's adaptive processes. METHODS: The data come from
      a general population sample (19,827 couples) and 15 years of follow-up data on
      marital dissolution. The following characteristics were investigated: Poor
      subjective health, obesity, heavy drinking, mental distress, lack of exercise,
      and smoking. Associations between these characteristics among husbands and wives
      and later divorce were investigated with Cox proportional hazards regression
      analyses. RESULTS: All the investigated characteristics except obesity were
      associated with marital dissolution. Moreover, spousal similarities in four of
      these characteristics (heavy drinking, mental distress, no exercise, and smoking)
      reduced the risk of divorce, compared to the combined main effects of husbands
      and wives. Nevertheless, couples concordant in these health issues still had
      higher risks of divorce than couples without these characteristics. CONCLUSION:
      Couples with similar health and health behavior are at a lower risk of divorce
      than are couples who are dissimilar in health. Health differences may thus be
      seen as vulnerabilities or stressors, supporting a health mismatch hypothesis.
      This study demonstrates that people who are similar to each other are more likely
      to stay together. Harmonizing partners' health behaviors may be a target in
      divorce prevention.

PMID- 25945252
TI  - Mood and cognition in healthy older European adults: the Zenith study.
AB  - BACKGROUND: The study aim was to determine if state and trait intra-individual
      measures of everyday affect predict cognitive functioning in healthy older
      community dwelling European adults (n = 387), aged 55-87 years. METHODS:
      Participants were recruited from centres in France, Italy and Northern Ireland.
      Trait level and variability in positive and negative affect (PA and NA) were
      assessed using self-administered PANAS scales, four times a day for four days.
      State mood was assessed by one PANAS scale prior to assessment of recognition
      memory, spatial working memory, reaction time and sustained attention using the
      CANTAB computerized test battery. RESULTS: A series of hierarchical regression
      analyses were carried out, one for each measure of cognitive function as the
      dependent variable, and socio-demographic variables (age, sex and social class),
      state and trait mood measures as the predictors. State PA and NA were both
      predictive of spatial working memory prior to looking at the contribution of
      trait mood. Trait PA and its variability were predictive of sustained attention.
      In the final step of the regression analyses, trait PA variability predicted
      greater sustained attention, whereas state NA predicted fewer spatial working
      memory errors, accounting for a very small percentage of the variance (1-2%) in
      the respective tests. CONCLUSION: Moods, by and large, have a small transient
      effect on cognition in this older sample.

PMID- 25945254
TI  - Finding meaning in life while living with HIV: validation of a novel HIV
      meaningfulness scale among HIV-infected participants living in Tennessee.
AB  - BACKGROUND: People living with HIV who maintain a positive outlook on their
      future may manage stress better than those who do not, leading to improved coping
      behaviors and better health outcomes. METHODS: While studying 125 HIV+ adults
      participating in two clinical trials of expressive writing we assessed their HIV
      specific meaningfulness of life with a short, unidimensional scale (the HIVMS).
      RESULTS: The HIVMS had a strong Cronbach's alpha (0.80) and acceptable test
      retest reliability (0.70). HIVMS scores were strongly correlated with measures of
      perceived control, optimism, and psychological well-being. Participants with
      lower HIVMS scores had higher probability of non-adherence to antiretroviral
      medication, suggesting a decreased ability to manage their illness successfully.
      Neither the control nor expressive writing intervention groups showed increased
      HIVMS scores. CONCLUSIONS: Future research is necessary to determine the effect
      of HIV meaning on long-term health outcomes and to develop interventions that can
      significantly improve a person's perception of their meaning in life.

PMID- 25945255
TI  - A case of Madelung's disease accompanied by Klinefelter's syndrome.
AB  - Madelung's disease is a rare fat metabolism disorder characterised by benign
      multiple symmetric, encapsulated lipomatosis. The exact cause of the disease is
      unknown; it may be associated with chronic alcoholism and mutations in
      mitochondrial DNA (A8344G), but there have been cases without these factors
      reported in the literature. A 29-year-old man with a 6-year history of diabetes
      mellitus was admitted to our hospital for poorly regulated diabetes and decreased
      libido. He was not an alcohol consumer. His family history was unremarkable.
      Physical examination revealed that he had a eunuchoid body shape. There was a
      symmetric excess fat accumulation in his submandibular, deltoid, nuchal,
      suprapubic and inguinal areas. He was diagnosed with Madelung's disease, and
      imaging studies supported the diagnosis. Hormonal evaluation revealed a
      hypergonadotropic hypogonadism. Karyotype analysis revealed a 47,XXY mutation.
      Genetic research showed no mitochondrial DNA mutation. Metabolic disorders, such
      as diabetes mellitus, hyperlipidaemia, hyperuricaemia and liver disease,
      endocrine gland diseases, such as hypothyroidism, and neurological diseases, such
      as polyneuropathy and cognitive disorders, may accompany Madelung's disease. The
      present study represents the first reported case of Madelung's disease
      accompanied by Klinefelter's syndrome. LEARNING POINTS: Madelung's disease is a
      rare fat metabolism disorder characterised by benign multiple symmetric and
      encapsulated lipid accumulation.The exact cause of the disease is
      unknown.Metabolic disorders, such as diabetes mellitus, hyperlipidaemia,
      hyperuricaemia and liver disease, endocrine gland diseases, such as
      hypothyroidism, and neurological diseases, such as polyneuropathy and cognitive
      disorders, may accompany Madelung's disease.

PMID- 25945256
TI  - 3-M syndrome: a novel CUL7 mutation associated with respiratory distress and a
      good response to GH therapy.
AB  - 3-M syndrome is a rare autosomal recessive disorder caused by mutations in the
      CUL7, OBSL1 and CCDC8 genes. It is characterised by growth failure, dysmorphic
      features and skeletal abnormalities. Data in the literature show variable
      efficacy of GH in the treatment of short stature. We report four Emirati siblings
      with the condition. The index case is a 10-year-old boy with characteristic
      features, including prenatal and postnatal growth failure, a triangular face, a
      long philtrum, full lips and prominent heels. Genetic testing confirmed a novel
      mutation (p.val88Ala) in the CUL7 gene. The parents are healthy, first-degree
      cousins with nine children, of whom two died in the first year of life with
      respiratory failure. Both had low birth weight and growth retardation. The boy's
      older sibling reached an adult height of 117 cm (-6.71 SDS). She was never
      treated with GH. He was started on GH treatment at 7 years of age, when his
      height was 94 cm (-5.3 SDS). 3-M syndrome should be considered in children with
      short stature who have associated dysmorphism and skeletal abnormalities. The
      diagnosis is more likely to occur in families that have a history of
      consanguinity and more than one affected sibling. Death in early infancy due to
      respiratory failure is another clue to the diagnosis, which might have a variable
      phenotype within a family. Genetic testing is important for confirming the
      diagnosis and for genetic counselling. GH treatment might be beneficial in
      improving stature in affected children. LEARNING POINTS: 3-M syndrome should be
      considered in families that have more than one sibling with short stature,
      particularly if there is consanguinity.Syndrome phenotype might be variable
      within a family with the same mutation.Genetic analysis is helpful in confirming
      diagnosis in the presence of variable siblings' phenotype.GH treatment might be
      useful in improving stature in 3-M syndrome.

PMID- 25945257
TI  - Incidence and Risk Factors for Delirium among Mechanically Ventilated Patients in
      an African Intensive Care Setting: An Observational Multicenter Study.
AB  - Aim. Delirium is common among mechanically ventilated patients in the intensive
      care unit (ICU). There are little data regarding delirium among mechanically
      ventilated patients in Africa. We sought to determine the burden of delirium and
      associated factors in Uganda. Methods. We conducted a multicenter prospective
      study among mechanically ventilated patients in Uganda. Eligible patients were
      screened daily for delirium using the confusional assessment method (CAM-ICU).
      Comparisons were made using t-test, chi-squares, and Fisher's exact test.
      Predictors were assessed using logistic regression. The level of statistical
      significance was set at P < 0.05. Results. Of 160 patients, 81 (51%) had
      delirium. Median time to onset of delirium was 3.7 days. At bivariate analysis,
      history of mental illness, sedation, multiorgan dysfunction, neurosurgery,
      tachypnea, low mean arterial pressure, oliguria, fevers, metabolic acidosis,
      respiratory acidosis, anaemia, physical restraints, marital status, and
      endotracheal tube use were significant predictors. At multivariable analysis,
      having a history of mental illness, sedation, respiratory acidosis, higher PEEP,
      endotracheal tubes, and anaemia predicted delirium. Conclusion. The prevalence of
      delirium in a young African population is lower than expected considering the
      high mortality. A history of mental illness, anaemia, sedation, endotracheal tube
      use, and respiratory acidosis were factors associated with delirium. 

PMID- 25945258
TI  - Health Resources and Strategies among Employed Women in Norway during Pregnancy
      and Early Motherhood.
AB  - The number of women in paid employment is increasing. However, when becoming a
      mother for the first time, many seem unprepared for the challenge of balancing
      motherhood and work as well as for the impact on their health. The aim of this
      study was to investigate the health resources and strategies of employed women in
      Norway during pregnancy and early motherhood by means of salutogenic theory. A
      hypothetical-deductive interpretive approach based on Antonovsky's salutogenic
      theory was applied in a secondary analysis. A total of six themes were
      identified; three were classified as health resources when experiencing tension
      and three as health strategies. Salutogenic theory seems to be a useful framework
      for illuminating the health resources and strategies adopted by employed women
      who become mothers. The identified health resources when experiencing tension and
      the health strategies applied may have implications for maternity care
      professionals and employers in promoting the health of such women and supporting
      them to combine work and family life. 

PMID- 25945259
TI  - Perceptions and realities for distal freehand interlocking of intramedullary
      nails.
AB  - There is a perception that distal freehand interlocking (DFHI) of intramedullary
      nails can be difficult and time consuming. This study consists of a survey of
      surgeons' practices for DFHI screws and their reasons for not using this
      technique. A survey was sent to 1400 orthopaedic surgeons who were asked to agree
      or disagree with statements regarding the difficulty and indications for the
      usage of distal freehand interlocking screws. The results were analyzed by
      practice demographics, resident availability, and completion of an orthopaedic
      trauma fellowship. Overall, 316 surgeons (22.6%) responded to the survey.
      Fellowship trained surgeons were 60% less likely to find DFHI difficult when
      compared to nonfellowship surgeons and surgeons with residents were 76% less
      likely to perceive DFHI as difficult than surgeons without residents. In all
      groups, 40-43% of surgeons used distal interlocking based on their comfort with
      the technique and not the fracture pattern. Distal freehand interlocking is
      perceived as difficult by community orthopaedic surgeons without residents and
      surgeons who have not done an orthopaedic trauma fellowship. Forty percent of
      surgeons based their usage of DFHI screws on their comfort with the technique and
      not the fracture pattern. 

PMID- 25945260
TI  - Neuroplastic effects of combined computerized physical and cognitive training in
      elderly individuals at risk for dementia: an eLORETA controlled study on resting
      states.
AB  - The present study investigates whether a combined cognitive and physical training
      may induce changes in the cortical activity as measured via electroencephalogram
      (EEG) and whether this change may index a deceleration of pathological processes
      of brain aging. Seventy seniors meeting the clinical criteria of mild cognitive
      impairment (MCI) were equally divided into 5 groups: 3 experimental groups
      engaged in eight-week cognitive and/or physical training and 2 control groups:
      active and passive. A 5-minute long resting state EEG was measured before and
      after the intervention. Cortical EEG sources were modelled by exact low
      resolution brain electromagnetic tomography (eLORETA). Cognitive function was
      assessed before and after intervention using a battery of neuropsychological
      tests including the minimental state examination (MMSE). A significant training
      effect was identified only after the combined training scheme: a decrease in the
      post- compared to pre-training activity of precuneus/posterior cingulate cortex
      in delta, theta, and beta bands. This effect was correlated to improvements in
      cognitive capacity as evaluated by MMSE scores. Our results indicate that
      combined physical and cognitive training shows indices of a positive neuroplastic
      effect in MCI patients and that EEG may serve as a potential index of gains
      versus cognitive declines and neurodegeneration. This trial is registered with
      ClinicalTrials.gov Identifier NCT02313935. 

PMID- 25945261
TI  - Modeling maintenance of long-term potentiation in clustered synapses: long-term
      memory without bistability.
AB  - Memories are stored, at least partly, as patterns of strong synapses. Given
      molecular turnover, how can synapses maintain strong for the years that memories
      can persist? Some models postulate that biochemical bistability maintains strong
      synapses. However, bistability should give a bimodal distribution of synaptic
      strength or weight, whereas current data show unimodal distributions for weights
      and for a correlated variable, dendritic spine volume. Thus it is important for
      models to simulate both unimodal distributions and long-term memory persistence.
      Here a model is developed that connects ongoing, competing processes of synaptic
      growth and weakening to stochastic processes of receptor insertion and removal in
      dendritic spines. The model simulates long-term (>1 yr) persistence of groups of
      strong synapses. A unimodal weight distribution results. For stability of this
      distribution it proved essential to incorporate resource competition between
      synapses organized into small clusters. With competition, these clusters are
      stable for years. These simulations concur with recent data to support the
      "clustered plasticity hypothesis" which suggests clusters, rather than single
      synaptic contacts, may be a fundamental unit for storage of long-term memory. The
      model makes empirical predictions and may provide a framework to investigate
      mechanisms maintaining the balance between synaptic plasticity and stability of
      memory.

PMID- 25945263
TI  - Penetrating Heart Injury due to Screwdriver Assault.
AB  - Penetrating heart injuries cause wounds in the cardiac chambers. Most of them are
      due to gunshot or stabbing by knives. Screwdriver is an uncommon weapon. Authors
      report a case of stab wound by screwdriver, treated at cardiovascular center in
      Dakar. This is a 16-year-old boy who experienced physical aggression. He was
      assaulted with a screwdriver and had stab wound on the anterior wall of the
      chest. Physical examination showed a screwdriver penetrating the sternum bone
      over a right angle. He had a mild pericardial blood effusion and a right
      ventricle wound 5 mm in diameter with transection of the right coronary vein. The
      screwdriver was removed without cardiopulmonary bypass (CPB) and the ventricle
      wound repaired by direct suture of stitches reinforced with Teflon pledgets. The
      right coronary artery was ligated. Postoperative period was free of events.
      Screwdriver is uncommonly used as a weapon. It is a dangerous device because of
      its rigid structure and narrow tip. 

PMID- 25945264
TI  - Multivessel spontaneous coronary artery dissection in an unlikely patient.
AB  - When approaching the symptom of acute onset chest pain in a previously healthy 26
      year-old male, anchoring heuristic presents a challenge to healthcare workers.
      This diagnostic error is the healthcare professional's tendency to rely on a
      previous diagnosis, and, in situations where a set of symptoms might mask a rare
      and deadly condition, this error can prove fatal for the patient. One such
      condition, Spontaneous Coronary Artery Dissection (SCAD), is an uncommon and
      malefic presentation of coronary artery disease that can lead to myocardial
      infarction and sudden death. We present a case of SCAD in an otherwise healthy 26
      year-old male who had been experiencing chest pain during and after sports
      activity. In the young, athletic male with SCAD, the danger of diagnostic error
      was a reality due to the broad symptomatology and the betraying demographics. 

PMID- 25945265
TI  - Partial PFO Closure for Persistent Hypoxemia in a Patient with Ebstein Anomaly.
AB  - Ebstein anomaly is characterized by deformities of the anterior leaflet of the
      tricuspid valve and atrialization of the right ventricle. Patients with severe
      tricuspid regurgitation are recommended to have tricuspid valve surgery with
      concomitant atrial septal defect closure. A 73-year-old female with Ebstein
      anomaly presented with severe hypoxemia. Transthoracic echocardiography revealed
      severe tricuspid regurgitation and a patent foramen ovale with right-to-left
      shunting. Complete percutaneous patent foramen ovale closure led to acute
      decompensation; however, partial closure led to hemodynamic stability and
      improved oxygenation. In conclusion, similar patients with "patent foramen ovale
      dependency" from longstanding shunts may benefit from partial patent foramen
      ovale closure. 

PMID- 25945262
TI  - Are visual peripheries forever young?
AB  - The paper presents a concept of lifelong plasticity of peripheral vision. Central
      vision processing is accepted as critical and irreplaceable for normal perception
      in humans. While peripheral processing chiefly carries information about motion
      stimuli features and redirects foveal attention to new objects, it can also take
      over functions typical for central vision. Here I review the data showing the
      plasticity of peripheral vision found in functional, developmental, and
      comparative studies. Even though it is well established that afferent projections
      from central and peripheral retinal regions are not established simultaneously
      during early postnatal life, central vision is commonly used as a general model
      of development of the visual system. Based on clinical studies and visually
      deprived animal models, I describe how central and peripheral visual field
      representations separately rely on early visual experience. Peripheral visual
      processing (motion) is more affected by binocular visual deprivation than central
      visual processing (spatial resolution). In addition, our own experimental
      findings show the possible recruitment of coarse peripheral vision for fine
      spatial analysis. Accordingly, I hypothesize that the balance between central and
      peripheral visual processing, established in the course of development, is
      susceptible to plastic adaptations during the entire life span, with peripheral
      vision capable of taking over central processing. 

PMID- 25945266
TI  - A rare case of intraosseous fibrolipoma of the mandible: diagnosis and treatment.
AB  - Lipomas are common soft tissue tumors. Intraosseous lipoma is a rare lesion that
      constitutes not more than 0.1% of bone tumors. It can occur anywhere in the body
      and there have only been a few cases found in the mandible. Intraosseous
      fibrolipoma of the jaw is an uncommon histological variant of the classic lipoma
      and to the best of our knowledge only one case has previously been reported in
      the literature. The cause of this lesion is uncertain. Clinically the lesion is
      generally asymptomatic and its radiographic feature is a well-defined
      radiolucency. Surgery is the treatment of choice. We present a case of an
      intraosseous fibrolipoma in the right mandibular ramus in a 25-year-old female. 

PMID- 25945267
TI  - Colonic Foreign Body Retrieval Using a Modified TAMIS Technique with Standard
      Instruments and Trocars.
AB  - Background. Reports of retained colorectal foreign bodies (CFBs) are no longer
      considered uncommon. We present a case where a retained CFB was retrieved using a
      modified TAMIS technique using standard instruments and trocars. Case Report. A
      52-year-old man presented with a CFB. We report our technique of extraction with
      standard laparoscopic instruments without specialized access platforms.
      Conclusions. This modified TAMIS technique is well suited for resource poor
      environments because it requires no specialized equipment, platforms, or
      additional skill sets compared to conventional laparoscopy. 

PMID- 25945268
TI  - Recurrent C. difficile in a Patient with IgG Deficiency.
AB  - IgG deficiency can predispose to recurrent pyogenic infections. The association
      of IgG deficiency with Clostridium difficile infection has been infrequently
      reported in the literature. We present a case of a middle-age woman with multiple
      hospitalizations for recurrent C. difficile in a short span of time which
      prompted consideration of a possible fecal transplant. On evaluation, she was
      found to have low total IgG, with subclass analysis revealing low IgG1 and IgG3.
      She was started on monthly infusions of immunoglobulins and one year after her
      last episode of C. difficile she has not had any recurrence. The role of
      immunoglobulin infusion in the treatment of recurrent C. difficile is
      controversial, with some studies revealing no clear evidence of benefit. Our case
      report suggests that the patients who have underlying IgG deficiency may benefit
      from immunoglobulin, as this can significantly reduce the incidence of recurrent
      infections and hence save the healthcare costs. 

PMID- 25945270
TI  - Tubocutaneous fistula.
AB  - Introduction. Tubocutaneous fistula is a very rare condition; most cases
      described in the literature are secondary to endometriosis, tuberculosis, and
      complications of child birth and gynecological operations. Case Presentation. We
      report a case of 40-year-old woman who presented with tubocutaneous fistula
      secondary to pelvic inflammatory disease which was diagnosed in the setting of
      persistent discharging wound in the right groin. Conclusion. Tubocutaneous
      fistula is a rare condition. Salpingectomy and resection of fistulous tract is
      the treatment of choice as is treating the underlying cause. Early diagnosis and
      treatment of these patients are essential for avoiding long term complications. 

PMID- 25945269
TI  - Danazol: an effective option in acquired amegakaryocytic thrombocytopaenic
      purpura.
AB  - Acquired amegakaryocytic thrombocytopaenic purpura (AATP) is a rare
      haematological condition characterised by isolated thrombocytopaenia with normal
      other cell lines. It is often initially misdiagnosed as immune thrombocytopaenic
      purpura but has characteristic bone marrow findings of reduced megakaryocyte
      numbers. The optimal treatment of AATP is not clearly defined but revolves around
      immunosuppressive therapies. We report a case of successful treatment of AATP
      with danazol, an antioestrogenic medication. We also review the aetiologies and
      pathogenesis of the disorder and suggest that danazol should be considered as an
      effective alternative to potent immunosuppression in AATP. 

PMID- 25945271
TI  - Rapid destruction of the humeral head caused by subchondral insufficiency
      fracture: a report of two cases.
AB  - Rapidly destructive arthritis (RDA) of the shoulder is a rare disease. Here, we
      report two cases, with different destruction patterns, which were most probably
      due to subchondral insufficiency fractures (SIFs). Case 1 involved a 77-year-old
      woman with right shoulder pain. Rapid destruction of both the humeral head and
      glenoid was seen within 1 month of the onset of shoulder pain. We diagnosed
      shoulder RDA and performed a hemiarthroplasty. Case 2 involved a 74-year-old
      woman with left shoulder pain. Humeral head collapse was seen within 5 months of
      pain onset, without glenoid destruction. Magnetic resonance imaging showed a bone
      marrow edema pattern with an associated subchondral low-intensity band, typical
      of SIF. Total shoulder arthroplasty was performed in this case. Shoulder RDA
      occurs as a result of SIF in elderly women; the progression of the joint
      destruction is more rapid in cases with SIFs of both the humeral head and the
      glenoid. Although shoulder RDA is rare, this disease should be included in the
      differential diagnosis of acute onset shoulder pain in elderly female patients
      with osteoporosis and persistent joint effusion. 

PMID- 25945272
TI  - Primary total knee arthroplasty twenty years after distal femoral cement
      augmentation of a giant cell tumor.
AB  - We present a case of knee reconstruction 20 years after treatment of a giant cell
      tumor (GCT) with curettage and cementation. There is currently an ongoing debate
      whether cement or allograft bone is the preferred material for filling the void
      after GCT curettage. In this case we were able to readily implant a primary total
      knee replacement without disturbing the existing well-interdigitated large cement
      bolus and did not require any stems or augments for the reconstruction. Given the
      ease of TKR implantation in this patient, we feel that the use of cement
      following curettage of a GCT lesion is a better choice than allograft bone which
      may not provide enough structural support for the knee reconstruction and lead to
      a much more extensive procedure. 

PMID- 25945273
TI  - A rarely seen multilevel thoracic vertebral fracture after a nocturnal
      hypoglycemic convulsion attack.
AB  - A 49-year-old male presented with acute midthoracic severe back pain following a
      witnessed nocturnal convulsion attack. There was no history of trauma and the
      patient had a 23-year history of Type I diabetes mellitus. MRI scans of the
      thoracic spine revealed compression fractures at T5, T6, T7, and T8 vertebrae.
      The patient was treated conservatively. At 17 months after the initial diagnosis,
      the complaints of back pain had been resolved and the patient was able to easily
      undertake daily living activities. Hypoglycaemia is a common problem in diabetic
      patients treated with insulin. Convulsions may occur as a consequence of insulin
      induced hypoglycemia. Nontraumatic compression fractures of the thoracic spine
      following seizures are a rare injury. Contractions of strong paraspinal muscles
      can lead to compression fracture of the midthoracic spine. Unrecognized
      hypoglycaemia should be considered to be a possible cause of convulsions in
      insulin-dependent diabetic patients. The aim of this report is to point out a
      case of rarely seen multilevel consecutive vertebrae fractures in a diabetic
      patient after a nocturnal hypoglycaemic convulsion attack. 

PMID- 25945275
TI  - Mature teratoma of the temporal bone in 3.5-month-old baby girl.
AB  - Mature teratoma is a benign germ cell tumor rarely located in the temporal bone.
      We are reporting a case of a mature teratoma of the temporal bone in a healthy
      borne 3.5-month-old baby girl with a 2-day suggestive history of otitis media and
      polypoidal mass expulsing from the external auditory canal of the left ear. A
      definitive diagnosis is made after complete excision and histological examination
      of the tissue. Total surgical excision of the tumor is the treatment of choice. 

PMID- 25945274
TI  - Inflammatory myofibroblastic tumor of the thigh: presentation of a rare case and
      review of the literature.
AB  - Inflammatory myofibroblastic tumors are uncommon neoplasms; presentation of these
      tumors in the lower extremities is extremely rare. We present a case of a 47-year
      old male with fever, fatigue, and a slow-growing thigh mass. The inflammatory
      markers were elevated and the MR images showed a well-defined intermuscular
      lesion with mild heterogeneous enhancement. The lesion was excised and histologic
      examination was consistent with an inflammatory myofibroblastic tumor. No
      adjuvant therapy was needed and the patient remained asymptomatic with no
      evidence of tumor recurrence during the 2 years of follow-up. 

PMID- 25945276
TI  - An interesting fistula tract presenting with recurrent gluteal abscess:
      instructive case.
AB  - A fistula extending from the gluteus to penis is an extremely rare entity. In
      this paper, we have highlighted novel variant of congenital penile to gluteal
      fistula complicated with gluteal and penoscrotal abscess in a previously healthy
      boy. A fistulous tract extending from the gluteus to penis has been shown by
      fistulogram. Bleomycin has been used in fistula tract with successful results in
      our patient. 

PMID- 25945277
TI  - Esophagojejunal anastomosis fistula, distal esophageal stenosis, and metalic
      stent migration after total gastrectomy.
AB  - Esophagojejunal anastomosis fistula is the main complication after a total
      gastrectomy. To avoid a complex procedure on friable inflamed perianastomotic
      tissues, a coated self-expandable stent is mounted at the site of the anastomotic
      leak. A complication of stenting procedure is that it might lead to distal
      esophageal stenosis. However, another frequently encountered complication of
      stenting is stent migration, which is treated nonsurgically. When the migrated
      stent creates life threatening complications, surgical removal is indicated. We
      present a case of a 67-year-old male patient who was treated at our facility for
      a gastric adenocarcinoma which developed, postoperatively, an esophagojejunostomy
      fistula, a distal esophageal stenosis, and a metallic coated self-expandable
      stent migration. To our knowledge, this is the first reported case of an
      esophagojejunostomy fistula combined with a distal esophageal stenosis as well as
      with a metallic coated self-expandable stent migration. 

PMID- 25945278
TI  - Leiomyoma of the renal vein: a rare tumor presenting as a renal mass.
AB  - Leiomyomas are benign mesenchymal tumors that rarely occur in the kidney. Renal
      leiomyomas usually occur in the renal cortex or capsule. They are less commonly
      found in the muscularis propria of the renal pelvis and cortical vascular smooth
      muscle. In this case report, we present a 41-year-old woman who had right flank
      pain and detected a mass in the right kidney hilum. 

PMID- 25945279
TI  - Malaria parasite density estimated with white blood cells count reference value
      agrees with density estimated with absolute in children less than 5 years in
      central ghana.
AB  - Introduction. The estimation of malaria parasite density using a microscope
      heavily relies on White Blood Cells (WBCs) counts. An assumed WBCs count of
      8000/uL has been accepted as reasonably accurate in estimating malaria parasite
      densities due to the challenge to accurately determine WBCs count. Method. The
      study used 4944 pieces of laboratory data of consented participants of age group
      less than 5 years. The study compared parasite densities of absolute WBCs,
      assumed WBCs, and the WBCs reference values in Central Ghana. Ethical approvals
      were given by three ethics committees. Results. The mean (+/-SD) WBCs and
      geometric mean parasite density (GMPD) were 10500/uL (+/-4.1) and 10644/uL (95%
      CI 9986/uL to 11346/uL), respectively. The difference in the GMPD compared using
      absolute WBCs and densities of assumed WBCs was significantly lower. The
      difference in GMPD obtained with an assumed WBCs count and that of the WBCs
      reference values for the study area, 10400/uL and 9200/uL for children in
      different age groups, were not significant. Discussion. Significant errors could
      result when assumed WBCs count is used to estimate malaria parasite density in
      children. GMPD generated with WBCs reference values statistically agreed with
      density from the absolute WBCs. When obtaining absolute WBC is not possible, the
      reference value can be used to estimate parasite density. 

PMID- 25945281
TI  - Iron Accumulation Is Not Homogenous among Patients with Parkinson's Disease.
AB  - Background. Iron is considered to lead to neurodegeneration and has been
      hypothesized as a possible cause of Parkinson's disease (PD). Susceptibility
      weighted imaging (SWI) is a powerful tool to measure phase related iron content
      of brain. Methods. Twelve de novo patients with PD were recruited from the
      Movement Disorders Clinic, Department of Neurology, Loma Linda University. Twelve
      age- and sex-matched non-PD subjects were recruited from neurology clinic as
      controls. Using SWI, the phase related iron content was estimated from different
      brain regions of interest (ROIs). Results. There was a trend between increasing
      age and iron accumulation in the globus pallidus and putamen in all subjects.
      Iron accumulation was not significant in different ROIs in PD patients compared
      to controls after adjustment for age. Our data revealed heterogeneity of phase
      values in different brain ROIs among all subjects with an exaggerated trend at SN
      in PD patients. Conclusions. Our data suggest a nonhomogeneous pattern of iron
      accumulation in different brain regions among PD patients. Further studies are
      needed to explore whether this may correlate to the progression of PD. To our
      knowledge, this is the first study demonstrating the heterogeneity of iron
      accumulation in the brain, among patients with PD. 

PMID- 25945280
TI  - Clinical Utility of Skin Biopsy in Differentiating between Parkinson's Disease
      and Multiple System Atrophy.
AB  - Background. It is often difficult to differentiate Parkinson's disease (PD) from
      multiple system atrophy (MSA), especially in their early stages. Objectives. To
      examine the clinical utility of histopathological analysis of biopsied skin from
      the chest wall and/or leg in differentiating between the two diseases. Methods.
      Skin biopsies from the lower leg and/or anterior chest wall were obtained from 38
      patients with idiopathic PD (26 treated with levodopa and 12 levodopa-naive) and
      13 age-matched patients with MSA. We sought aggregates of phosphorylated alpha
      synuclein on cutaneous nerve fibers using double fluorescence
      immunohistochemistry and confocal microscopy and measured intraepidermal nerve
      fiber density (IENFD). Results. Phosphorylated alpha-synuclein aggregates were
      identified on cutaneous nerves in two patients with PD (5.3%) but in none of the
      patients with MSA, and IENFD was significantly lower in patients with PD when
      compared to those with MSA. There was no difference in IENFD between levodopa
      treated and levodopa-naive patients with PD. Conclusions. Our findings suggest
      that an assessment of IENFD in biopsied skin could be a useful means of
      differentiating between PD and MSA but that detection of alpha-synuclein
      aggregates on cutaneous nerves in the distal sites of the body is insufficiently
      sensitive. 

PMID- 25945282
TI  - Headspace-Solid-Phase Microextraction-Gas Chromatography as Analytical
      Methodology for the Determination of Volatiles in Wild Mushrooms and Evaluation
      of Modifications Occurring during Storage.
AB  - Mushrooms are sources of food, medicines, and agricultural means. Not much is
      reported in the literature about wild species of the Mediterranean flora,
      although many of them are traditionally collected for human consumption. The
      knowledge of their chemical constituents could represent a valid tool for both
      taxonomic and physiological characterizations. In this work, a headspace-solid
      phase microextraction (HS-SPME) method coupled with GC-MS and GC-FID was
      developed to evaluate the volatile profiles of ten wild mushroom species
      collected in South Italy. In addition, in order to evaluate the potential of this
      analytical methodology for true quantitation of volatiles, samples of the
      cultivated species Agaricus bisporus were analyzed. The choice of this mushroom
      was dictated by its ease of availability in the food market, due to the
      consistent amounts required for SPME method development. For calibration of the
      main volatile compounds, the standard addition method was chosen. Finally, the
      assessed volatile composition of A. bisporus was monitored in order to evaluate
      compositional changes occurring during storage, which represents a relevant issue
      for such a wide consumption edible product. 

PMID- 25945283
TI  - Keratinocyte Migration and a Hypothetical New Role for Extracellular Heat Shock
      Protein 90 Alpha in Orchestrating Skin Wound Healing.
AB  - Significance: The treatment and care of patients with skin wounds are a major
      healthcare expenditure. Burn wounds, iatrogenic surgical wounds, venous stasis
      dermatitis ulcers, diabetic lower limb ulcers, pressure ulcers, and skin wounds
      from peripheral neuropathies are largely treated with only supportive care.
      Despite a great deal of research into using growth factors as therapeutic agents,
      to date, the field has been disappointing. The only biologic agent that is
      Federal Drug Administration (FDA) approved for promoting skin wound healing is
      recombinant platelet-derived growth factor (PDGF-BB), but its modest efficacy and
      expense limit its use clinically. Recent Advances: Acute hypoxia induced by the
      clotting of dermal blood vessels during the wounding of skin is a major stress
      factor that leads to the re-programming of basal keratinocytes to initiate re
      epithelialization. The laterally migrating keratinocytes secrete extracellular
      heat shock protein 90 alpha. Heat shock protein 90 alpha (hsp90alpha) engages low
      density lipoprotein receptor-related protein-1 (LRP-1) cellular receptors and
      works as an autocrine factor to stimulate keratinocyte migration (re
      epithelialization) and as a paracrine factor to stimulate the migration of dermal
      fibroblasts (fibroplasia) and microvascular endothelial cells (neo
      vascularization). Hypoxia-triggered extracellular heat shock protein 90 alpha
      acts as the master regulator of initial skin wound healing. Critical Issues: It
      is not yet known how the engagement of hsp90alpha with the LRP-1 receptor leads
      to increased motility of keratinocytes, fibroblasts, or microvascular endothelial
      cells. Understanding the sequence of how an acute skin wound via hypoxic stress
      leads to cellular events that ultimately induce accelerated wound closure
      provides numerous targets for new wound-healing therapeutic agents. Future
      Directions: Developing data for an investigational new drug (IND) application to
      the FDA for a Phase I study using hsp90alpha in human skin wounds. Identifying
      the cellular signaling mechanisms by which hsp90alpha enhances skin cell
      migration, leading to accelerated wound closure.

PMID- 25945284
TI  - The Roles of Growth Factors in Keratinocyte Migration.
AB  - Significance: The re-epithelialization of wounded skin requires the rapid and
      coordinated migration of keratinocytes (KC) into the wound bed. Almost
      immediately after wounding, cells present at or attracted to the wound site begin
      to secrete a complex milieu of growth factors. These growth factors exert
      mitogenic and motogenic effects on KCs, inducing the rapid proliferation and
      migration of KCs at the wound edge. Recent Advances: New roles for growth factors
      in KC biology are currently being discovered and investigated. This review will
      highlight the growth factors, particularly transforming growth factor-alpha (TGF
      alpha), heparin-binding epidermal growth factor (HB-EGF), insulin-like growth
      factor 1 (IGF-1), fibroblast growth factor 7 (FGF-7), FGF-10, and hepatocyte
      growth factor (HGF), which have conclusively been shown to be the most motogenic
      for KCs. Critical Issues: The cellular and molecular heterogeneity of wounded
      tissue makes establishing direct relationships between specific growth factors
      and KC migration difficult in situ. The absence of this complexity in simplified
      in vitro experimental models of migration makes the clinical relevance of the
      results obtained from these in vitro studies ambiguous. Future Directions:
      Deciphering the relationship between growth factors and KC migration is critical
      for understanding the process of wound healing in normal and disease states.
      Insights into the basic science of the effects of growth factors on KC migration
      will hopefully lead to the development of new therapies to treat acute and
      chronic wounds.

PMID- 25945285
TI  - Metalloproteinases and Wound Healing.
AB  - Significance: Matrix metalloproteinases (MMPs) are present in both acute and
      chronic wounds. They play a pivotal role, with their inhibitors, in regulating
      extracellular matrix degradation and deposition that is essential for wound
      reepithelialization. The excess protease activity can lead to a chronic
      nonhealing wound. The timed expression and activation of MMPs in response to
      wounding are vital for successful wound healing. MMPs are grouped into eight
      families and display extensive homology within these families. This homology
      leads in part to the initial failure of MMP inhibitors in clinical trials and the
      development of alternative methods for modulating the MMP activity. MMP-knockout
      mouse models display altered wound healing responses, but these are often subtle
      phenotypic changes indicating the overlapping MMP substrate specificity and inter
      MMP compensation. Recent Advances: Recent research has identified several new MMP
      modulators, including photodynamic therapy, protease-absorbing dressing, microRNA
      regulation, signaling molecules, and peptides. Critical Issues: Wound healing
      requires the controlled activity of MMPs at all stages of the wound healing
      process. The loss of MMP regulation is a characteristic of chronic wounds and
      contributes to the failure to heal. Future Directions: Further research into how
      MMPs are regulated should allow the development of novel treatments for wound
      healing.

PMID- 25945286
TI  - Syndecan-1 and Its Expanding List of Contacts.
AB  - Significance: The binding of cytokines and growth factors to heparan sulfate (HS)
      chains on proteoglycans generates gradients that control development and regulate
      wound healing. Syndecan-1 (sdc1) is an integral membrane HS proteoglycan. Its
      structure allows it to bind with cytosolic, transmembrane, and extracellular
      matrix (ECM) proteins. It plays important roles in mediating key events during
      wound healing because it regulates a number of important processes, including
      cell adhesion, cell migration, endocytosis, exosome formation, and fibrosis.
      Recent Advances: Recent studies reveal that sdc1 regulates wound healing by
      altering integrin activation. Differences in integrin activation lead to cell
      type-specific changes in the rate of cell migration and ECM assembly. Sdc1 also
      regulates endocytosis and the formation and release of exosomes. Critical Issues:
      Understanding how sdc1 facilitates wound healing and resolution will improve
      treatment options for elderly and diabetic patients with delayed wound healing.
      Studies showing that sdc1 function is altered in cancer are relevant to those
      interested in controlling fibrosis and scarring. Future Directions: The key to
      understanding the various functions ascribed to sdc1 is resolving how it
      interacts with its numerous binding partners. The role played by chondroitin
      sulfate glycosaminoglycan (GAG) chains on the ability of sdc1 to associate with
      its ligands needs further investigation. At wound sites heparanase can cleave the
      HS GAG chains of sdc1, alter its ability to bind cytokines, and induce shedding
      of the ectodomain. This review will discuss how the unique structure of sdc1
      allows it to play key roles in cell signaling, ECM assembly, and wound healing.

PMID- 25945289
TI  - The treatment of perilunate injuries.

PMID- 25945288
TI  - Epidermal Wound Healing in the Nematode Caenorhabditis elegans.
AB  - Significance: Healing of epidermal wounds is a fundamentally conserved process
      found in essentially all multicellular organisms. Studies of anatomically simple
      and genetically tractable model invertebrates can illuminate the roles of key
      genes and mechanisms in wound healing. Recent Advances: The nematode skin is
      composed of a simple epithelium, the epidermis (also known as hypodermis), and an
      associated extracellular cuticle. Nematodes likely have a robust capacity for
      epidermal repair; yet until recently, relatively few studies have directly
      analyzed wound healing. Here we review epidermal wound responses and repair in
      the model nematode Caenorhabditis elegans. Critical Issues: Wounding the
      epidermis triggers a cutaneous innate immune response and wound closure. The
      innate immune response involves upregulation of a suite of antimicrobial
      peptides. Wound closure involves a Ca2+-triggered rearrangement of the actin
      cytoskeleton. These processes appear to be initiated independently, yet, their
      coordinated activity allows the animal to survive otherwise fatal skin wounds.
      Future Directions: Unanswered questions include the nature of the damage
      associated molecular patterns sensed by the epidermis, the signaling pathways
      relaying Ca2+ to the cytoskeleton, and the mechanisms of permeability barrier
      repair.

PMID- 25945287
TI  - Laminins: Roles and Utility in Wound Repair.
AB  - Significance: Laminins are complex extracellular macromolecules that are major
      players in the control of a variety of core cell processes, including regulating
      rates of cell proliferation, differentiation, adhesion, and migration. Laminins,
      and related extracellular matrix components, have essential roles in tissue
      homeostasis; however, during wound healing, the same proteins are critical
      players in re-epithelialization and angiogenesis. Understanding how these
      proteins influence cell behavior in these different conditions holds great
      potential in identifying new strategies to enhance normal wound closure or to
      treat chronic/nonhealing wounds. Recent Advances: Laminin-derived bioactive
      peptides and, more recently, laminin-peptide conjugated scaffolds, have been
      designed to improve tissue regeneration after injuries. These peptides have been
      shown to be effective in decreasing inflammation and granulation tissue, and in
      promoting re-epithelialization, angiogenesis, and cell migration. Critical
      Issues: Although there is now a wealth of knowledge concerning laminin form and
      function, there are still areas of some controversy. These include the relative
      contribution of two laminin-based adhesive devices (focal contacts and
      hemidesmosomes) to the re-epithelialization process, the impact and implications
      of laminin proteolytic processing, and the importance of laminin polymer
      formation on cell behavior. In addition, the roles in wound healing of the
      laminin-related proteins, netrins, and LaNts are still to be fully defined.
      Future Directions: The future of laminin-based therapeutics potentially lies in
      the bioengineering of specific substrates to support laminin deposition for ex
      vivo expansion of autologous cells for graft formation and transplantation.
      Significant recent advances suggest that this goal is within sight.

PMID- 25945290
TI  - Perilunate dislocations treated with external fixation and percutaneous pinning.
AB  - Background The purpose of this study was to review clinical and radiographic
      outcomes of perilunate dislocations (PLDs) and fracture-dislocations (PLFDs)
      treated with external fixation and Kirschner wires (K-wires). Materials and
      Methods Twenty patients (18 males and 2 females) with a mean age of 38 years
      (range 18-59) with an acute PLD or PLFD were treated with external fixator and K
      wires. There were 12 PLDs and seven transscaphoid and one transstyloid PLFDs. The
      median time from trauma to operation was 8 hours (range 2-12 hours). Indirect
      reduction via ligamentotaxis was achieved in 17 patients with a mean age of
      38years (range 18-59). There were 12 PLDs and 5 trans-scaphoid PLFDs; however, in
      three cases (two transscaphoid and one transstyloid PLFDs), indirect reduction
      failed and an open reduction was required. The intercarpal ligaments were not
      repaired even after open reduction. Results The mean follow-up was 39 months
      (range 18-68 months). The flexion-extension range of motion (ROM) and grip
      strength of the injured wrist averaged 80% and 88%, respectively, of the
      corresponding values for the contralateral wrists. According to Cooney's scoring
      system, overall functional outcomes of the 17 patients were rated as excellent in
      4 patients, good in 8, fair in 4, and poor in 1. Fifteen patients returned to
      their former occupations. Two patients with a trans-scaphoid perilunate injury
      developed nonunion of the scaphoid, and two developed posttraumatic arthritis.
      Conclusion External fixation plus percutaneous K-wires for the treatment of acute
      PLDs has satisfactory midterm functional and radiographic outcomes. When
      successful, this minimally invasive technique is simple and provides restoration
      of the carpal alignment. It may especially be useful in the polytrauma patient,
      thanks to its decreased operative time and diminished blood loss, when other
      emergent surgical procedures may be necessary. An open reduction with possible
      fixation may be necessary for PLDs and PLFDs, especially in the presence of
      polytrauma and scaphoid comminution. LEVEL OF EVIDENCE: IV.

PMID- 25945291
TI  - Arthroscopic treatment of perilunate dislocations and fracture dislocations.
AB  - Background The key to a successful result in the treatment of perilunate
      dislocations (PLDs) and fracture-dislocations (PLFDs) is the restoration of
      normal alignment of the carpal bones, followed by stable maintenance until
      healing. This article aimed to assess whether arthroscopic techniques are a
      reliable surgical option for the treatment of this challenging injury. Materials
      and Methods Twenty patients with an acute PLD or PLFD were treated by an
      arthroscopic technique. They were retrospectively reviewed at an average follow
      up of 31.2 months (range 18-61 months). Functional outcomes were assessed with
      the Modified Mayo Wrist Score (MMWS), Disabilities of the Arm, Shoulder, and Hand
      (DASH) questionnaire, and Patient-Rated Wrist Evaluation (PRWE) score as well as
      radiographic evaluations. Description of Technique Arthroscopic reduction and
      percutaneous fixation was performed to the scapholunate and lunotriquetral
      intervals using Kirschner wires (K-wires) as joysticks as well as to the scaphoid
      using a cannulated headless screw for transscaphoid-type injuries. The K-wires
      were removed at 10 weeks postoperation. Results Overall functional outcomes
      according to the MMWS were rated as excellent in three patients, good in eight,
      fair in seven, and poor in two. The mean DASH score was 18, and the mean PRWE
      score was 30. On the basis of radiographic parameters, reduction obtained at the
      operation was maintained within normal ranges in 15 patients. No patient had
      developed arthritis by the last follow-up. Conclusions The medium-term results
      show that arthroscopic treatment can provide proper restoration and stable
      fixation of carpal alignment and results in satisfactory functional and
      radiologic outcomes for acute perilunate injuries. Level of Evidence Level IV. 

PMID- 25945292
TI  - Factors associated with unplanned reoperation in perilunate dislocations and
      fracture dislocations.
AB  - Background Perilunate injuries are complex and uncommon injuries that are
      typically the result of a high-energy injury and are nearly always treated
      operatively. Little is known about factors associated with unplanned reoperations
      after surgery for perilunate injuries. Purpose To assess the rate and types of
      unplanned reoperation after operative treatment of a perilunate dislocation.
      Patients and Methods We reviewed 115 patients of all ages with unplanned
      reoperations after operative treatment of perilunate injuries at five hospitals.
      Planned removal of implants were not considered as unplanned reoperations.
      Results Sixteen patients had an unplanned reoperation, including four for
      compartment syndrome (three hand, one forearm); three for deep infection; three
      for malalignment or an errant screw; two for early salvage procedures; and four
      for other reasons. We considered seven unplanned reoperations necessary (forearm
      compartment syndrome, infection, loss of alignment, errant screw) and nine
      debatable or unnecessary (hand compartment syndrome, early salvage procedures,
      suspected malunion, etc.). Patients who had an unplanned reoperation were younger
      (median age 24 versus 34 years; p = 0.0034); had earlier surgery (median days to
      surgery 0 versus 3; p = 0.0068); and were more likely injured in a motor vehicle
      collision (50% versus 17%; p = 0.0070). Accounting for interaction among the
      variables using multivariable analysis, the factors independently associated with
      unplanned reoperation were young age (odds ratio 0.92) and motor vehicle
      collision accidents (odds ratio 4.1). Conclusion We conclude that higher-energy
      injuries may be at greater risk for unplanned reoperation, but more than half of
      the unplanned reoperations were for debatable indications. Level III
      Retrospective Cohort Review. 

PMID- 25945293
TI  - Arthroscopically assisted mini-invasive management of perilunate dislocations.
AB  - Purpose The purpose of this study was to evaluate the outcomes of perilunate
      dislocations and fracture-dislocations treated with arthroscopically assisted
      mini-invasive reduction and fixation. Methods Between June 2012 and May 2014, 24
      patients who had a dorsal perilunate dislocation or fracture-dislocation were
      treated with arthroscopically assisted reduction and percutaneous fixation. The
      mean follow-up was 14.8 months (range 6-32 months). Clinical outcomes were
      evaluated on the basis of range of motion; grip strength; Mayo Wrist Score; Quick
      Disabilities of the Arm, Shoulder and Hand (QuickDASH) questionnaire; and Patient
      Rated Wrist Evaluation (PRWE) score. Radiographic evaluations included time to
      scaphoid union, carpal alignments, and any development of arthritis. Results The
      range of flexion-extension motion of the injured wrist averaged 86% of the values
      for the contralateral wrist. The grip strength of the injured wrist averaged 83%
      of the values for the contralateral wrists. The mean QuickDASH score was 6, and
      the mean PRWE score was 10. According to the Mayo Wrist Scores, overall
      functional outcomes were rated as excellent in 13 patients (54%), good in 6
      (25%), fair in 4 (17%), and poor in 1 (4%). Scaphoid nonunion developed in one
      patient. Reduction obtained during the operation was maintained within normal
      ranges in all patients. Arthritis had not developed in any patient at final
      follow-up. Conclusions Arthroscopically assisted mini-invasive reduction with
      percutaneous fixation is a reliable and favorable alternative in the treatment of
      perilunate injuries according to our early follow-up results. LEVEL OF EVIDENCE:
      Level IV, Therapeutic.

PMID- 25945294
TI  - The role of arthroscopy for treatment of perilunate injuries.
AB  - Background Open reduction with internal fixation (ORIF) is currently the gold
      standard treatment of acute perilunate injuries (PLIs). Less invasive surgery,
      including arthroscopic techniques, has recently emerged in the hope that results
      similar to those of ORIF could be obtained with less tissue disturbance. Our
      purpose was to review retrospectively a series of selected PLIs treated with
      arthroscopic assistance over the past 10 years. Materials and Methods Between
      2004 and 2014, a total of 135 acute PLIs were surgically treated in our unit. A
      total of 27 patients were treated with arthroscopic assistance, among whom 18
      were reviewed clinically and radiologically. Description of Technique After an
      initial closed gross reduction, radio- and midcarpal arthroscopy were performed
      to clean up the debris and assess the cartilaginous, bony, and ligamentous
      damage. In 22 cases arthroscopy was followed by either radiolunate and
      lunotriquetral pinning, scapholunate ligament repair, and SL joint pinning or
      ORIF of a scaphoid fracture through a mini-invasive dorsal approach. In the
      remaining six cases, fixation of the ligamentous and/or bony injuries was done
      using arthroscopy alone. Results Arthroscopic findings are presented as well as
      the clinical results in a subgroup of patients. At final follow-up, visual analog
      scale (VAS) pain was rated 18/100 on average (minimum 0, maximum 50). If we
      consider only the patients without reflex sympathetic dystrophy (RSD; n = 14),
      the average active wrist flexion-extension was 87 degrees  (58% of the normal
      contralateral side) and the average grip strength was 30 kg (71% of the normal
      contralateral side). Conclusions Although no statistical comparisons were made,
      we found that the results were similar to those of ORIF. The results of our study
      suggest that the use of arthroscopy to treat selected PLIs may be a reliable
      adjunct either alone or in combination with a dorsal mini-open approach. 

PMID- 25945295
TI  - Arthroplasty for fifth carpometacarpal joint arthritis.
AB  - Background Fifth-carpometacarpal (CMC)-joint fractures and dislocations can
      produce carpometacarpal joint arthritis. The purpose of this study was to
      evaluate the radiographic and clinical outcomes of arthroplasty for fifth
      carpometacarpal joint arthritis. Material and Methods A series of six patients
      who had symptomatic advanced fifth-CMC arthritis and had failed to respond to
      conservative treatment. All patients underwent Dupert's technique of fifth-CMC
      arthroplasty with a mean follow-up of 17.6 months. Results were reviewed
      clinically and radiographically. Results Union between the fourth and fifth
      metacarpals was observed at an average of 6.2 weeks after surgery. Grip strength
      improved. Range of motion (ROM) of the fifth metacarpophalangeal (MCP) joint and
      the fifth metacarpal height remained unchanged. Visual analog scale (VAS) results
      improved significantly. Conclusion Despite the medium-term follow-up and small
      number of patients, our results suggest fifth-CMC arthroplasty with arthrodesis
      of the fourth and fifth metacarpal bases may be a reliable procedure for fifth
      CMC arthritis. 

PMID- 25945296
TI  - Low-intensity pulsed ultrasound treatment for scaphoid fracture nonunions in
      adolescents.
AB  - Background Treatment of scaphoid nonunion is challenging, leading clinicians to
      pursue innovation in surgical technique and adjunctive therapies to improve union
      rates. Purpose The purpose of this study was to investigate the use of low
      intensity pulsed ultrasound as an adjunctive treatment modality following
      surgical treatment of scaphoid nonunion in adolescent patients, for whom this
      therapy has not yet been FDA-approved. Patients and Methods We performed a
      retrospective review of adolescent patients with scaphoid nonunion treated
      surgically followed by adjunctive low-intensity pulsed ultrasound therapy. All
      patients underwent 20 minutes of daily ultrasound therapy postoperatively until
      there was evidence of bony healing, based on both clinical and radiographic
      criteria. Final healing was confirmed by > 50% bone bridging on CT scan. Results
      Thirteen of fourteen (93%) patients healed at a mean interval of 113 days (range
      61-217 days). There were no surgical or postoperative complications. One patient
      developed heterotopic bone formation about the scaphoid. Conclusions Our study
      suggests that low-intensity pulsed ultrasound therapy can safely be utilized as
      an adjunctive modality in adolescents to augment scaphoid healing following
      surgical intervention. Level of Evidence Level IV, Case series. 

PMID- 25945297
TI  - An anatomic and kinematic analysis of a new total wrist arthroplasty design.
AB  - Background Total wrist arthroplasty (TWA) is a viable surgical treatment for
      disabling wrist arthritis. While current designs are a notable improvement from
      prior generations, radiographic loosening and failures remain a concern. Purpose
      The purpose of this investigation is to evaluate a new total wrist arthroplasty
      design kinematically. The kinematic function of a native, intact cadaveric wrist
      was compared with that of the same wrist following TWA. Method Six, fresh-frozen
      wrist cadaveric specimens were utilized. Each wrist was fixed to an experimental
      table and its range of motion, axis of rotation, and muscle moment arms were
      calculated. The following tendons were attached to the apparatus to drive motion:
      extensor carpi radialis longus (ECRL), extensor carpi radialis brevis (ECRB),
      extensor carpi ulnaris (ECU), flexor carpi radialis (FCR), flexor carpi ulnaris
      (FCU), and abductor pollicis longus (APL). The wrist was then manually moved
      along a guide by an experimenter through a series of motions including flexion
      extension, radial-ulnar deviation, and circumduction. The experiment was then
      performed on the specimen following implantation of the TWA. Results Following
      the TWA procedure, there were statistically significant decreases in the ulnar
      deviation and the flexion/ulnar deviation component of dart throw ranges of
      motion. There were no statistically significant changes in flexion, extension,
      radial deviation, the extension/radial deviation component of the dart thrower
      motion, or the circumduction range of motion. Conclusions Kinematic analysis of
      the new TWA suggests that a stable, functional wrist is achievable with this
      design. Clinical Relevance While appreciating the limitations of a cadaveric
      study, this investigation indicates that the TWA design studied merits study in
      human populations. 

PMID- 25945298
TI  - The long-term outcome of four-corner fusion.
AB  - Introduction Four-corner arthrodesis with excision of the scaphoid is an accepted
      salvage procedure for scapholunate advanced collapse (SLAC) and scaphoid nonunion
      advanced collapse (SNAC) and has been performed in our unit for over 20 years. We
      have undertaken a retrospective review of 116 of these procedures performed in
      110 patients between 1992 and 2009. Fifty-eight patients attended for a clinical
      evaluation, and 29 responded by postal questionnaire. Methods The surgical
      technique undertaken was standard. That is, through a dorsal approach the
      scaphoid and tip of the radial styloid were excised. The capitate, lunate,
      triquetrum, and hamate articular surfaces were then prepared down to bleeding
      bone. Bone grafts from the scaphoid and radial styloid were then inserted and
      fixation undertaken. For the latter, various methods were used, including
      Kirschner (K-)wires, staples, bone screws, but predominantly the Spider plate
      (Integra Life Sciences, USA). Thereafter the wrist was immobilized for a minimum
      period of 2 weeks prior to rehabilitation. Results Follow-up was done at a mean
      of 9 years and 4 months (range 3-19 years). All patients reported a significant
      improvement in pain relief and ~50% of flexion extension, although only 40% of
      radioulnar deviation. Grip strength was again ~50% of the contralateral side.
      Most patients reported a significant improvement in function with 87% returning
      to work. In addition, radiologic evaluation identified 28 patients (31%) who
      demonstrated ongoing signs of nonunion, particularly around the triquetrum.
      Fourteen of these (15%) underwent a further procedure, generally with success.
      Finally, none of the patients demonstrated any arthritic changes in the lunate
      fossa on follow-up X-ray, and all secondary procedures were undertaken within 2
      years of the primary. Discussion This research has demonstrated that four-corner
      fusion fixed with a circular plate can result in a satisfactory outcome with a
      reduction in pain, a functional range of motion, and a satisfactory functional
      outcome. The bulk of the complications appear to occur in the first 2 years after
      surgery. Thereafter, analysis shows long-term satisfaction with little
      deterioration. Nonunion, particularly around the triquetrum, continues to be a
      problem, but it may be that this bone should be excised along with the scaphoid,
      resulting in a three-part fusion only. Alternatively, a simple capitolunate
      fusion may be satisfactory. 

PMID- 25945299
TI  - Periprosthetic fracture of the ulna-a case report.
AB  - After resection of the radial head, the load transmission through the forearm is
      changed dramatically. Most of the axial load is transmitted to the ulna. This can
      happen through the interosseous membrane, if intact, thus preventing proximal
      migration of theradius. However, radial head resection entails some slacking of
      the interosseous membrane, thereby reducing its ability to transmit load. In
      traumatic lesions of the interosseous membrane there is no limit to the proximal
      migration of the radius until the ulnar head abuts on the carpus. In both cases
      the load transmitted by the ulna increases dramatically and can promote fractures
      thereof. A 52-year-old, right-handed male patient presented with a periprosthetic
      fracture of the right ulna 6 weeks after implantation of an ulna head prosthesis.
      He had previously undergone radial head excision for malunion of the radial head
      and secondary humeroradial osteoarthritis. This operation had reduced pain and
      improved the range of motion at the elbow but entailed degenerative arthritis and
      related symptoms at the distal radioulnar joint (DRUJ). From the spectrum of
      possible treatment options, ulnar head resurfacing/hemiprosthesis was elected and
      performed without intraoperative or postoperative irregularities. However, 6
      weeks postoperatively, as he was lifting a heavy object, a periprosthetic
      fracture of the ulna occurred, which ultimately was treated successfully by open
      reduction and plate fixation. Plate fixation of periprosthetic fractures is an
      established treatment concept after excluding implant loosening. Periprosthetic
      fracture of the ulna seems to be a rare complication but can be treated
      similarly. 

PMID- 25945300
TI  - Dorsal dislocation of the trapezoid at the scaphotrapeziotrapezoidal joint.
AB  - Background Axial dislocations of the trapezoid are rare, high-energy injuries. We
      present an unusual case of isolated dorsal dislocation of the trapezoid and index
      metacarpal at the scaphotrapeziotrapezoidal (STT) joint due to steering wheel
      injury. Case Description A 56-year-old man presented to our office with right
      hand pain for 10 days after a head-on motor vehicle accident (MVA) in which he
      suffered an axial load injury to his hand on the steering wheel. X-ray images
      were reported as unremarkable. Further workup with computed tomography (CT) scan
      revealed an isolated dorsal dislocation of the trapezoid with its associated
      index metacarpal at the STT joint. The patient was treated with open reduction,
      pinning, and dorsal capsulodesis. Literature Review Dorsal dislocation of the
      trapezoid has been associated with high-energy trauma such as industrial
      accidents or motorcycle accidents; however, recent case reports have also
      revealed an axial loading mechanism from a steering wheel injury as an
      increasingly common mechanism. These cases typically occur concomitantly with
      other fractures or dislocations of the carpal bones or carpometacarpal (CMC)
      joints. Multiple reports of delayed diagnoses due to distracting injuries and
      difficulty of recognition on plain radiographs have been reported. Clinical
      Relevance Dorsal dislocation of the trapezoid with its associated second
      metacarpal is a rare, high-energy injury that can often be missed on plain
      radiography. We report a rare variant with no concomitant injury to the
      metacarpals or carpal bones. A low index of suspicion for further imaging should
      exist in the setting of an axial loading injury to the hand. 

PMID- 25945301
TI  - Arthroscopic Knotless Peripheral Ulnar-Sided TFCC Repair.
AB  - This article describes the indications and technique for all-arthroscopic
      knotless repair of a peripheral tear to the triangular fibrocartilage complex
      (TFCC). The advantage of this technique is that it allows repair of the articular
      disk back to the fovea of the ulna without any suture knots to irritate the
      patient. The learning curve is steep, but once learned, this technique can be
      performed very quickly and is faster. There are no knots to irritate the patient,
      and in the author's opinion, there is quicker pain relief than with other
      techniques. 

PMID- 25945302
TI  - Erratum: The Management of Kienbock Disease: A Survey of the ASSH Membership.
AB  - [This corrects the article DOI: 10.1055/s-0035-1544225.]. 

PMID- 25945303
TI  - Tiludronate concentrations and cytologic findings in synovial fluid after
      intravenous regional limb perfusion with tiludronate in horses.
AB  - Anecdotal accounts of tiludronate administration via intravenous regional limb
      perfusion (IVRLP) exist despite a lack of information regarding safety for
      synovial structures in the perfused area. The objective of this study was to
      determine whether tiludronate concentrations in synovial structures after IVRLP
      with low dose (0.5 mg, LDT) or high dose (50 mg, HDT) tiludronate remain below a
      value demonstrated in vitro to be safe for articular cartilage (<19,000 ng/ml),
      and to determine effects of tiludronate on synovial fluid cytology variables
      compared to saline perfused control limbs. Using a randomized controlled
      experimental study design, horses received IVRLP with LDT (n = 6) or HDT (n = 6)
      in one forelimb and IVRLP with saline in the contralateral limb. Synovial fluid
      cytology variables and tiludronate concentrations were evaluated in navicular
      bursae (NB), and distal interphalangeal (DIP) and metacarpophalangeal (MCP)
      joints one week before and 30-45 min after IVRLP, and in DIP and MCP joints 24 h
      after IVRLP. Data were analyzed with 2-way rmANOVA (p < 0.05). Highest measured
      synovial fluid tiludronate concentrations occurred 30-45 min post-perfusion. Mean
      tiludronate concentrations were lower in LDT limbs (MCP = 39.6 +/- 14.3 ng/ml,
      DIP = 118.1 +/- 66.6 ng/ml, NB = 82.1 +/- 30.2 ng/ml) than in HDT limbs (MCP =
      3,745.1 +/- 1,536.6 ng/ml, DIP = 16,274.0 +/- 5,460.2 ng/ml, NB = 6,049.3 +/-
      1,931.7 ng/ml). Tiludronate concentration was >19,000 ng/ml in DIP joints of two
      HDT limbs. Tiludronate was measurable only in synovial fluid from HDT limbs 24 h
      post-perfusion. There were no differences in synovial fluid cytology variables
      between control and treated limbs. Conclusions. In some horses, IVRLP with HDT
      may result in synovial fluid concentrations of tiludronate that may have adverse
      effects on articular cartilage, based on in vitro data. IVRLP with LDT is
      unlikely to promote articular cartilage degradation. Further studies to determine
      a safe and effective dose for IVRLP with tiludronate are needed. 

PMID- 25945304
TI  - Organization and distribution of glomeruli in the bowhead whale olfactory bulb.
AB  - Although modern baleen whales (Mysticeti) retain a functional olfactory system
      that includes olfactory bulbs, cranial nerve I and olfactory receptor genes,
      their olfactory capabilities have been reduced to a great degree. This reduction
      likely occurred as a selective response to their fully aquatic lifestyle. The
      glomeruli that occur in the olfactory bulb can be divided into two non
      overlapping domains, a dorsal domain and a ventral domain. Recent molecular
      studies revealed that all modern whales have lost olfactory receptor genes and
      marker genes that are specific to the dorsal domain. Here we show that olfactory
      bulbs of bowhead whales (Balaena mysticetus) lack glomeruli on the dorsal side,
      consistent with the molecular data. In addition, we estimate that there are more
      than 4,000 glomeruli elsewhere in the bowhead whale olfactory bulb, which is
      surprising given that bowhead whales possess only 80 intact olfactory receptor
      genes. Olfactory sensory neurons that express the same olfactory receptors in
      rodents generally project to two specific glomeruli in an olfactory bulb,
      implying an approximate 1:2 ratio of the number of olfactory receptors to the
      number of glomeruli. Here we show that this ratio does not apply to bowhead
      whales, reiterating the conceptual limits of using rodents as model organisms for
      understanding the initial coding of odor information among mammals. 

PMID- 25945305
TI  - Indirect effects of overfishing on Caribbean reefs: sponges overgrow reef
      building corals.
AB  - Consumer-mediated indirect effects at the community level are difficult to
      demonstrate empirically. Here, we show an explicit indirect effect of overfishing
      on competition between sponges and reef-building corals from surveys of 69 sites
      across the Caribbean. Leveraging the large-scale, long-term removal of sponge
      predators, we selected overfished sites where intensive methods, primarily fish
      trapping, have been employed for decades or more, and compared them to sites in
      remote or marine protected areas (MPAs) with variable levels of enforcement.
      Sponge-eating fishes (angelfishes and parrotfishes) were counted at each site,
      and the benthos surveyed, with coral colonies scored for interaction with
      sponges. Overfished sites had >3 fold more overgrowth of corals by sponges, and
      mean coral contact with sponges was 25.6%, compared with 12.0% at less-fished
      sites. Greater contact with corals by sponges at overfished sites was mostly by
      sponge species palatable to sponge predators. Palatable species have faster rates
      of growth or reproduction than defended sponge species, which instead make
      metabolically expensive chemical defenses. These results validate the top-down
      conceptual model of sponge community ecology for Caribbean reefs, as well as
      provide an unambiguous justification for MPAs to protect threatened reef-building
      corals. An unanticipated outcome of the benthic survey component of this study
      was that overfished sites had lower mean macroalgal cover (23.1% vs. 38.1% for
      less-fished sites), a result that is contrary to prevailing assumptions about
      seaweed control by herbivorous fishes. Because we did not quantify herbivores for
      this study, we interpret this result with caution, but suggest that additional
      large-scale studies comparing intensively overfished and MPA sites are warranted
      to examine the relative impacts of herbivorous fishes and urchins on Caribbean
      reefs. 

PMID- 25945306
TI  - Temporal changes in nasopharyngeal carriage of Streptococcus pneumoniae serotype
      1 genotypes in healthy Gambians before and after the 7-valent pneumococcal
      conjugate vaccine.
AB  - Streptococcus pneumoniae serotype 1 is one of the leading causes of invasive
      pneumococcal disease. However, this invasive serotype is hardly found in
      nasopharyngeal asymptomatic carriage and therefore large epidemiological studies
      are needed to assess the dynamics of serotype 1 infection. Within the context of
      a large cluster randomized trial conducted in rural Gambia to assess the impact
      of PCV-7 vaccination on nasopharyngeal carriage, we present an ancillary analysis
      describing the prevalence of nasopharyngeal carriage of pneumococcal serotype 1
      and temporal changes of its more frequent genotypes. Nasopharyngeal swabs (NPS)
      were collected before PCV-7 vaccination (December 2003-May 2004) and up to 30
      months after PCV-7 vaccination. The post-vaccination time was divided in three
      periods to ensure an equal distribution of the number of samples: (1) July 2006
      March 2007, (2) April 2007-March 2008 and (3) April 2008-Feb 2009. S. pneumoniae
      serotype 1 were genotyped by MLST. Serotype 1 was recovered from 87 (0.71%) of
      12,319 NPS samples collected. In the pre-vaccination period, prevalence of
      serotype 1 was 0.47% in both study arms. In the post-vaccination periods,
      prevalence in the fully vaccinated villages ranged between 0.08% in period 1 and
      0.165% in period 2, while prevalence in partly vaccinated villages was between
      0.17% in period 3 and 1.34% in period 2. Overall, four different genotypes were
      obtained, with ST3081 the most prevalent (60.71%), followed by ST618 (29.76%).
      ST3081 was found only in post-vaccination period 2 and 3, while ST618 had
      disappeared in post-vaccination period 3. Distribution of these major genotypes
      was similar in both study arms. Emergence of ST3081 and concomitant disappearance
      of ST618 may suggest a change in the molecular epidemiology of pneumococcal
      serotype 1 in this region. This change is not likely to be associated with the
      introduction of PCV-7 which lacks serotype 1, as it was observed simultaneously
      in both study arms. Future population-based epidemiological studies will provide
      further evidence of substantive changes in the pneumococcal serotype 1
      epidemiology and the likely mechanisms. 

PMID- 25945307
TI  - Tunable translational control using site-specific unnatural amino acid
      incorporation in Escherichia coli.
AB  - Translation of target gene transcripts in Escherichia coli harboring UAG amber
      stop codons can be switched on by the amber-codon-specific incorporation of an
      exogenously supplied unnatural amino acid, 3-iodo-L-tyrosine. Here, we report
      that this translational switch can control the translational efficiency at any
      intermediate magnitude by adjustment of the 3-iodo-L-tyrosine concentration in
      the medium, as a tunable translational controller. The translational efficiency
      of a target gene reached maximum levels with 10(-5) M 3-iodo-L-tyrosine, and
      intermediate levels were observed with suboptimal concentrations (approximately
      spanning a 2-log10 concentration range, 10(-7)-10(-5) M). Such intermediate-level
      expression was also confirmed in individual bacteria. 

PMID- 25945308
TI  - Demographic rates of northern royal albatross at Taiaroa Head, New Zealand.
AB  - Demographic rates, such as annual survival rate, are generally difficult to
      estimate for long-lived seabirds, because of the length of time required for this
      kind of study and the remoteness of colonies. However, a small colony of northern
      royal albatross (Diomedea sanfordi) established itself on the mainland of New
      Zealand at Taiaroa Head, making possible regular banding and monitoring of its
      individuals since the first chick fledged, in 1938. Data on the presence/absence
      of birds, as well as on breeding outcomes, were available for the period from
      1989-90 to 2011-12, and included 2128 annual resightings of 355 banded
      individuals of known age. The main goal of the present study was to estimate the
      annual survival rate of juveniles, pre-breeders, and adults at Taiaroa Head.
      These rates were estimated simultaneously in a single Bayesian multi-state
      capture-recapture model. Several models were fitted to the data, with different
      levels of complexity. From the most parsimonious model, the overall annual adult
      survival rate was estimated as 0.950 (95% CI [0.941-0.959]). In this model, adult
      survival declined with age, from 0.976 (95% CI [0.963-0.988]) at 6 years, the
      minimum age at first breeding, to 0.915 (95% CI [0.879-0.946]) at 40 years. Mean
      annual survival of pre-breeders was 0.966 (95% CI [0.950-0.980]), and 0.933 (95%
      CI [0.908-0.966]) for juveniles. There was no discernible difference in survival
      between males and females, and there was no apparent trend in survival over time.
      Estimates of other demographic rates were also obtained during the estimation
      process. The mean age at first return of juveniles to the colony was estimated as
      4.8 years (95% CI [4.6-5.1]), and the mean age at first breeding as 8.9 years
      (95% CI [8.5-9.3]). Because all the birds of the colony were banded, it was
      possible to estimate the total population size. The number of northern royal
      albatross present annually at the Taiaroa Head colony has doubled since 1989-90,
      and the current total population size was estimated to be over 200 individuals.
      The ratio of the total population size to the number of annual breeding pairs
      varied from 5 to 12 among years, with an overall mean of 7.65 (95% CI [7.56
      7.78]), and this high variability highlights the need for a sufficient number of
      surveys of seabird breeding populations before reliable conclusions on population
      trends can be made. Although long-term data allowed estimates of demographic
      rates of northern royal albatross at Taiaroa Head, the location of the colony and
      the ongoing management by staff mean that the population dynamics may differ from
      those of the main population on the Chatham Islands. 

PMID- 25945309
TI  - The association between lifetime cigarette smoking and dysphonia in the Korean
      general population: findings from a national survey.
AB  - This study aims to investigate the relationship between current smoking and
      lifetime amount smoked and the incidence of dysphonia using data from a national
      cross-sectional survey that represents the Korean population. Subjects were 3,600
      non-institutionalised civilian adults over the age of 19 (1,501 males and 2,099
      females) who completed the laryngeal examination of the 2008 Korea National
      Health and Nutrition Examination Survey (KNHANES). For lifetime amount smoked,
      subjects were classified as light smokers (<=26.7 pack years), medium smokers
      (26.7-40.5 pack years), heavy smokers (40.5-55.5 pack years), and very heavy
      smokers (55.5-156 pack years) based on pack years (packs smoked per day * years
      as a smoker). The odds ratio (OR) for the statistical test was presented using
      hierarchical logistic regression. When adjusted for covariates (age, gender,
      level of education, income, occupation, alcohol consumption and pain/discomfort
      during the last two weeks), current smokers had a 1.8 times (OR = 1.77, 95% CI
      [1.17-2.68]) higher risk for self-reported voice problems than non-smokers.
      Moreover, current smokers had a 1.6 times (OR = 1.56, 95% CI [1.02-2.38]) higher
      risk of laryngeal disorder (p < 0.05). In terms of pack years, very heavy smokers
      were significantly more likely to have laryngeal disorder, while self-reported
      voice problems were significantly more likely for heavy smokers but not very
      heavy smokers. The results of this study imply that chronic smoking has a
      significant relationship with dysphonia. Longitudinal studies are required in
      future work to verify the causality between lifetime smoking amount and
      dysphonia. 

PMID- 25945310
TI  - Physician consultation in young children with recurrent pain-a population-based
      study.
AB  - Background. Recurrent pain is a common experience in childhood, but only few
      children with recurrent pain attend a physician. Previous studies yielded
      conflicting findings with regard to predictors of health care utilization in
      children with recurrent pain. Methods. The present study analyzes data from the
      German Health Interview and Examination Survey for Children and Adolescents
      (KiGGS) study comprising n = 2,149 children (3-10 years old) with recurrent pain
      to find robust predictors. We used multiple logistic regressions to investigate
      age, gender, socio-economic status (SES), migration background, pain intensity,
      pain frequency, pain-related disability, mental health problems, and health
      related quality of life (HRQL) as predictors for visiting a doctor due to pain.
      Results. Overall, young girls with high pain-related disability, intensity,
      frequency, and migration background were more likely to attend a physician. Pain
      related disability had the largest impact. Socioeconomic status, health-related
      quality of life and mental health problems were not systematically related to
      health care utilization. An analysis of the variability of these results
      indicated that several hundred participants are needed until the results
      stabilize. Conclusions. Our findings highlight the importance of pain-related
      disability and frequency in assessing the severity of recurrent pain. Generic
      predictors and demographic variables are of lesser relevance to children with
      recurrent pain. On a methodological level, our results show that large-scale
      studies are need to reliably identify predictors of health care utilization. 

PMID- 25945311
TI  - An elaborate data set on human gait and the effect of mechanical perturbations.
AB  - Here we share a rich gait data set collected from fifteen subjects walking at
      three speeds on an instrumented treadmill. Each trial consists of 120 s of normal
      walking and 480 s of walking while being longitudinally perturbed during each
      stance phase with pseudo-random fluctuations in the speed of the treadmill belt.
      A total of approximately 1.5 h of normal walking (>5000 gait cycles) and 6 h of
      perturbed walking (>20,000 gait cycles) is included in the data set. We provide
      full body marker trajectories and ground reaction loads in addition to a
      presentation of processed data that includes gait events, 2D joint angles,
      angular rates, and joint torques along with the open source software used for the
      computations. The protocol is described in detail and supported with additional
      elaborate meta data for each trial. This data can likely be useful for validating
      or generating mathematical models that are capable of simulating normal periodic
      gait and non-periodic, perturbed gaits. 

PMID- 25945312
TI  - Analysis of pollen-specific alternative splicing in Arabidopsis thaliana via semi
      quantitative PCR.
AB  - Alternative splicing enables a single gene to produce multiple mRNA isoforms by
      varying splice site selection. In animals, alternative splicing of mRNA isoforms
      between cell types is widespread and supports cellular differentiation. In
      plants, at least 20% of multi-exon genes are alternatively spliced, but the
      extent and significance of tissue-specific splicing is less well understood,
      partly because it is difficult to isolate cells of a single type. Pollen is a
      useful model system to study tissue-specific splicing in higher plants because
      pollen grains contain only two cell types and can be collected in large amounts
      without damaging cells. Previously, we identified pollen-specific splicing
      patterns by comparing RNA-Seq data from Arabidopsis pollen and leaves. Here, we
      used semi-quantitative PCR to validate pollen-specific splicing patterns among
      genes where RNA-Seq data analysis indicated splicing was most different between
      pollen and leaves. PCR testing confirmed eight of nine alternative splicing
      patterns, and results from the ninth were inconclusive. In four genes,
      alternative transcriptional start sites coincided with alternative splicing. This
      study highlights the value of the low-cost PCR assay as a method of validating
      RNA-Seq results. 

PMID- 25945313
TI  - Plant-insect interactions from Middle Triassic (late Ladinian) of Monte Agnello
      (Dolomites, N-Italy)-initial pattern and response to abiotic environmental
      perturbations.
AB  - The Paleozoic-Mesozoic transition is characterized by the most massive extinction
      of the Phanerozoic. Nevertheless, an impressive adaptive radiation of herbivorous
      insects occurred on gymnosperm-dominated floras not earlier than during the
      Middle to Late Triassic, penecontemporaneous with similar events worldwide, all
      which exhibit parallel expansions of generalized and mostly specialized insect
      herbivory on plants, expressed as insect damage on a various plant organs and
      tissues. The flora from Monte Agnello is distinctive, due to its preservation in
      subaerially deposited pyroclastic layers with exceptionally preserved details.
      Thus, the para-autochthonous assemblage provides insights into environmental
      disturbances, caused by volcanic activity, and how they profoundly affected the
      structure and composition of herbivory patterns. These diverse Middle Triassic
      biota supply extensive evidence for insect herbivore colonization, resulting in
      specific and complex herbivory patterns involving the frequency and diversity of
      20 distinctive damage types (DTs). These DT patterns show that external foliage
      feeders, piercer-and-suckers, leaf miners, gallers, and oviposition culprits were
      intricately using almost all tissue types from the dominant host plants of
      voltzialean conifers (e.g., Voltzia), horsetails, ferns (e.g., Neuropteridium,
      Phlebopteris, Cladophlebis and Thaumatopteris), seed ferns (e.g., Scytophyllum),
      and cycadophytes (e.g., Bjuvia and Nilssonia). 

PMID- 25945314
TI  - From Lucy to Kadanuumuu: balanced analyses of Australopithecus afarensis
      assemblages confirm only moderate skeletal dimorphism.
AB  - Sexual dimorphism in body size is often used as a correlate of social and
      reproductive behavior in Australopithecus afarensis. In addition to a number of
      isolated specimens, the sample for this species includes two small associated
      skeletons (A.L. 288-1 or "Lucy" and A.L. 128/129) and a geologically
      contemporaneous death assemblage of several larger individuals (A.L. 333). These
      have driven both perceptions and quantitative analyses concluding that Au.
      afarensis was markedly dimorphic. The Template Method enables simultaneous
      evaluation of multiple skeletal sites, thereby greatly expanding sample size, and
      reveals that A. afarensis dimorphism was similar to that of modern humans. A new
      very large partial skeleton (KSD-VP-1/1 or "Kadanuumuu") can now also be used,
      like Lucy, as a template specimen. In addition, the recently developed Geometric
      Mean Method has been used to argue that Au. afarensis was equally or even more
      dimorphic than gorillas. However, in its previous application Lucy and A.L.
      128/129 accounted for 10 of 11 estimates of female size. Here we directly compare
      the two methods and demonstrate that including multiple measurements from the
      same partial skeleton that falls at the margin of the species size range
      dramatically inflates dimorphism estimates. Prevention of the dominance of a
      single specimen's contribution to calculations of multiple dimorphism estimates
      confirms that Au. afarensis was only moderately dimorphic. 

PMID- 25945316
TI  - Morphological diversity in tenrecs (Afrosoricida, Tenrecidae): comparing tenrec
      skull diversity to their closest relatives.
AB  - It is important to quantify patterns of morphological diversity to enhance our
      understanding of variation in ecological and evolutionary traits. Here, we
      present a quantitative analysis of morphological diversity in a family of small
      mammals, the tenrecs (Afrosoricida, Tenrecidae). Tenrecs are often cited as an
      example of an exceptionally morphologically diverse group. However, this
      assumption has not been tested quantitatively. We use geometric morphometric
      analyses of skull shape to test whether tenrecs are more morphologically diverse
      than their closest relatives, the golden moles (Afrosoricida, Chrysochloridae).
      Tenrecs occupy a wider range of ecological niches than golden moles so we predict
      that they will be more morphologically diverse. Contrary to our expectations, we
      find that tenrec skulls are only more morphologically diverse than golden moles
      when measured in lateral view. Furthermore, similarities among the species-rich
      Microgale tenrec genus appear to mask higher morphological diversity in the rest
      of the family. These results reveal new insights into the morphological diversity
      of tenrecs and highlight the importance of using quantitative methods to test
      qualitative assumptions about patterns of morphological diversity. 

PMID- 25945315
TI  - Phylogeographic structure and northward range expansion in the barnacle
      Chthamalus fragilis.
AB  - The barnacle Chthamalus fragilis is found along the US Atlantic seaboard
      historically from the Chesapeake Bay southward, and in the Gulf of Mexico. It
      appeared in New England circa 1900 coincident with warming temperatures, and is
      now a conspicuous member of rocky intertidal communities extending through the
      northern shore of Cape Cod, Massachusetts. The origin of northern C. fragilis is
      debated. It may have spread to New England from the northern end of its historic
      range through larval transport by ocean currents, possibly mediated by the
      construction of piers, marinas, and other anthropogenic structures that provided
      new hard substrate habitat. Alternatively, it may have been introduced by fouling
      on ships originating farther south in its historic distribution. Here we examine
      mitochondrial cytochrome c oxidase I sequence diversity and the distribution of
      mitochondrial haplotypes of C. fragilis from 11 localities ranging from Cape Cod,
      to Tampa Bay, Florida. We found significant genetic structure between northern
      and southern populations. Phylogenetic analysis revealed three well-supported
      reciprocally monophyletic haplogroups, including one haplogroup that is
      restricted to New England and Virginia populations. While the distances between
      clades do not suggest cryptic speciation, selection and dispersal barriers may be
      driving the observed structure. Our data are consistent with an expansion of C.
      fragilis from the northern end of its mid-19th century range into Massachusetts. 

PMID- 25945317
TI  - Median nerve behavior at different wrist positions among older males.
AB  - The effect of wrist flexion-extension on the median nerve appearance, namely the
      cross-sectional area (MNCSA) and the longitudinal (D1) and vertical (D2)
      diameters, was investigated among older adults (N = 34). Ultrasound examination
      was conducted to examine the median nerve at different wrist angles (neutral; and
      15 degrees , 30 degrees , and 45 degrees  extension and flexion), in both the
      dominant and nondominant hand. Median nerve behavior were significantly
      associated with wrist angle changes. The MNCSA at wrist flexion and extension
      were significantly smaller (P < .001) compared with the neutral position in both
      the dominant and nondominant hand. The D1 and D2 were significantly reduced at
      flexion (P < .001) and extension (P < .001), respectively, in both the dominant
      and nondominant hand. Our results suggest that a larger flexion-extension angle
      causes higher compression stress on the median nerve, leading to increased
      deformation of the MNCSA, D1, and D2 among older adults. 

PMID- 25945318
TI  - Inductive heating kills cells that contribute to plaque: a proof-of-concept.
AB  - Inducing cell death by heating targeted particles shows promise in cancer
      treatment. Here, we aim to demonstrate the feasibility of extending the use of
      this technique to treat and remove vascular deposits and thrombosis. We used
      induction heating of macrophages, which are key contributors to atherosclerosis
      and have demonstrated clear feasibility for heating and destroying these cells
      using ferromagnetic and pure iron particles. Specifically, iron particles
      achieved maximum temperatures of 51 +/- 0.5  degrees C and spherical particles
      achieved a maximum temperature of 43.9 +/- 0.2  degrees C (N = 6) after 30 min of
      inductive heating. Two days of subsequent observation demonstrated that inductive
      heating led to a significant reduction in cell number. Prior to induction
      heating, cell density was 105,000 +/- 20,820 cells/ml (N = 3). This number was
      reduced to 6,666 +/- 4,410 cells/ml for the spherical particles and 16,666 +/-
      9,280 cells/ml for the iron particles 24 h after inductive heating. Though cell
      density increased on the second day following inductive heating, the growth was
      minimal. Cells grew to 26,667 +/- 6,670 cells/ml and 30,000 +/- 15,280 cells/ml
      respectively. Compared to cell cultures with iron and spherical particles that
      were not subjected to induction heating, we observed a 97% reduction in cell
      count for the spherical particles and a 91% reduction for the iron particles
      after the first 24 h. After 48 h we observed a 95% reduction in cell growth for
      both spherical and iron particles. Induction heating of microparticles was thus
      highly effective in reducing the macrophage population and preventing their
      growth. These results demonstrate the feasibility of targeting cells involved in
      atherosclerosis and warrant further research into potential clinical
      applications. 

PMID- 25945319
TI  - Profile analysis of hepatic porcine and murine brain tissue slices obtained with
      a vibratome.
AB  - This study is aimed at characterizing soft tissue slices using a vibratome. In
      particular, the effect of two sectioning parameters (i.e., step size and
      sectioning speed) on resultant slice thickness was investigated for fresh porcine
      liver as well as for paraformaldehyde-fixed (PFA-fixed) and fresh murine brain. A
      simple framework for embedding, sectioning and imaging the slices was established
      to derive their thickness, which was evaluated through a purposely developed
      graphical user interface. Sectioning speed and step size had little effect on the
      thickness of fresh liver slices. Conversely, the thickness of PFA-fixed murine
      brain slices was found to be dependent on the step size, but not on the
      sectioning speed. In view of these results, fresh brain tissue was sliced varying
      the step size only, which was found to have a significant effect on resultant
      slice thickness. Although precision-cut slices (i.e., with regular thickness)
      were obtained for all the tissues, slice accuracy (defined as the match between
      the nominal step size chosen and the actual slice thickness obtained) was found
      to increase with tissue stiffness from fresh liver to PFA-fixed brain. This
      quantitative investigation can be very helpful for establishing the most suitable
      slicing setup for a given tissue. 

PMID- 25945320
TI  - The European and Japanese outbreaks of H5N8 derive from a single source
      population providing evidence for the dispersal along the long distance bird
      migratory flyways.
AB  - The origin of recent parallel outbreaks of the high pathogenicity H5N8 avian flu
      virus in Europe and in Japan can be traced to a single source population, which
      has most likely been spread by migratory birds. By using Bayesian coalescent
      methods to analyze the DNA sequences of the virus to find the times for
      divergence and combining this sequence data with bird migration data we can show
      the most likely locations and migratory pathways involved in the origin of the
      current outbreak. This population was most likely located in the Siberian summer
      breeding grounds of long-range migratory birds. These breeding grounds provide a
      connection between different migratory flyways and explain the current outbreaks
      in remote locations. By combining genetic methods and epidemiological data we can
      rapidly identify the sources and the dispersion pathways for novel avian
      influenza outbreaks. 

PMID- 25945321
TI  - Patterns of response to aripiprazole, lithium, haloperidol, and placebo across
      factor scores of mania.
AB  - BACKGROUND: A previous factor analysis of Young Mania Rating Scale and Montgomery
      Asberg Depression Rating Scale items identified composite factors of depression,
      mania, sleep disturbance, judgment/impulsivity, and irritability/hostility as
      major components of psychiatric symptoms in acute mania or mixed episodes in a
      series of trials of antipsychotics. However, it is unknown whether these factors
      predict treatment outcome. METHODS: Data from six double-blind, randomized,
      controlled clinical trials with aripiprazole in acute manic or mixed episodes in
      adults with bipolar I disorder were pooled for this analysis and the previously
      identified factors were examined for their value in predicting treatment outcome.
      Treatment efficacy was assessed for aripiprazole (n = 1,001), haloperidol (n =
      324), lithium (n = 155), and placebo (n = 694) at baseline, days 4, 7, and 10,
      and then weekly to study end. Mean change in factor scores from baseline to week
      3 was assessed by receiver operating characteristics curves for percentage factor
      change at day 4 and week 1. RESULTS: Subjects receiving aripiprazole,
      haloperidol, and lithium significantly improved mania factor scores versus
      placebo. Factors most predictive of endpoint efficacy for aripiprazole were
      judgment/impulsivity at day 4 and mania at week 1. Optimal factor score
      improvement for outcome prediction was approximately 40% to 50%. Early efficacy
      predicted treatment outcome across all factors; however, response at week 1 was a
      better predictor than response at day 4. CONCLUSIONS: This analysis confirms
      clinical benefits in early treatment/assessment for subjects with bipolar mania
      and suggests that certain symptom factors in mixed or manic episodes may be most
      predictive of treatment response.

PMID- 25945322
TI  - Resistin - 420 C/G polymorphism and serum resistin level in Iranian patients with
      gestational diabetes mellitus.
AB  - BACKGROUND: Resistin is a circulating adipokine with insulin-antagonizing
      effects. The aim of this study was to investigate the relationship between the
      single nucleotide polymorphism (SNP) -420C > G in the resistin gene with serum
      resistin levels, insulin resistance, and risk of gestational diabetes (GDM) in
      Iranian population. METHOD: 75 GDM patients and 70 healthy pregnant women were
      enrolled in this study. Genotyping for SNP- 420C > G in the resistin gene was
      performed by the polymerase chain reaction- restriction fragment length
      polymorphism (PCR-RFLP) method. Serum resistin and insulin were measured by
      immunoassay. Blood glucose levels and lipid profile were measured by enzymatic
      methods. Homeostasis model of assessment for insulin resistance (HOMA-IR) were
      calculated. RESULT: GG genotype and G allele of SNP-420C > G were more frequent
      in GDM patients compared to non-GDM subjects. Serum resistin level was similar in
      GDM and non-GDM patients. The serum levels of resistin in GDM and non-GDM women
      with GG genotype were similar to those with GC + CC genotype. Multivariate
      logistic regression analysis after adjusting for confounding factors showed a
      higher susceptibility to GDM in patients with GG genotype compared to subjects
      with GG + GT genotype (odds ratio = 4.59, 95% CI; 1.96-10.71, p = 0.00). Serum
      resistin level was correlated with serum triglyceride, total and low density
      lipoprotein (LDL) cholesterol (p < 0.05) in GDM patients. No significant
      association was found between serum resistin, insulin resistance, and SNP-420C >
      G. CONCLUSION: The SNP-420C/G of resistin gene is associated with genetic
      susceptibility to GDM in our population. Further studies are necessary to confirm
      the role of this polymorphism in pathogenesis of GDM and to explore potential
      mechanisms by which it modulates susceptibility to GDM.

PMID- 25945323
TI  - Combination therapies for the management of nocturia and its comorbidities.
AB  - Nocturia is the most bothersome lower urinary tract symptom. It has a
      multifactorial etiology. It had been thought nocturia was a nonspecific symptom
      of lower urinary system dysfunction, but it has been determined that many
      diseases, related to different organ systems, might be reasons for this
      nonspecific symptom. Along with the importance of systemic diseases that cause
      nocturia, the symptom itself has adverse effects on patients' health and quality
      of life. There are several studies reporting a direct relationship between
      nocturia and depression, cognitive dysfunction, mood disturbances, falls, and
      fractures. For this reason, it is important to treat nocturia both to increase
      quality of life and to decrease related complications. Treatment opportunities
      have been under investigation for 20 years. Most of the studies in the literature
      have reported the results of single-drug medication on nocturia, which may be
      insufficient for a situation that has such a multifactorial etiology. In this
      review, we evaluated the success of different treatment combinations on nocturia.

PMID- 25945324
TI  - An alumina toughened zirconia composite for dental implant application: in vivo
      animal results.
AB  - Ceramic materials are widely used for biomedical applications because of their
      remarkable biological and mechanical properties. Composites made of alumina and
      zirconia are particularly interesting owing to their higher toughness with
      respect to the monolithic materials. On this basis, the present study is focused
      on the in vivo behavior of alumina toughened zirconia (ATZ) dental implants
      treated with a hydrothermal process. A minipig model was implemented to assess
      the bone healing through histology and mRNA expression at different time points
      (8, 14, 28, and 56 days). The novel ATZ implant was compared to a titanium
      clinical standard. The implants were analyzed in terms of microstructure and
      surface roughness before in vivo tests. The most interesting result deals with a
      statistically significant higher digital histology index for ATZ implants with
      respect to titanium standard at 56 days, which is an unprecedented finding, to
      the authors' knowledge. Even if further investigations are needed before
      proposing the clinical use in humans, the tested material proved to be a
      promising candidate among the possible ceramic dental implants. 

PMID- 25945325
TI  - Non-transfusion-dependent thalassemia: a complex mix of genetic entities yet to
      be fully discovered.

PMID- 25945326
TI  - Interplay of the Gastric Pathogen Helicobacter pylori with Toll-Like Receptors.
AB  - Toll-like receptors (TLRs) are crucial for pathogen recognition and downstream
      signaling to induce effective immunity. The gastric pathogen Helicobacter pylori
      is a paradigm of persistent bacterial infections and chronic inflammation in
      humans. The chronicity of inflammation during H. pylori infection is related to
      the manipulation of regulatory cytokines. In general, the early detection of H.
      pylori by TLRs and other pattern recognition receptors (PRRs) is believed to
      induce a regulatory cytokine or chemokine profile that eventually blocks the
      resolution of inflammation. H. pylori factors such as LPS, HSP-60, NapA, DNA, and
      RNA are reported in various studies to be recognized by specific TLRs. However,
      H. pylori flagellin evades the recognition of TLR5 by possessing a conserved N
      terminal motif. Activation of TLRs and resulting signal transduction events lead
      to the production of pro- and anti-inflammatory mediators through activation of
      NF-kappaB, MAP kinases, and IRF signaling pathways. The genetic polymorphisms of
      these important PRRs are also implicated in the varied outcome and disease
      progression. Hence, the interplay of TLRs and bacterial factors highlight the
      complexity of innate immune recognition and immune evasion as well as regulated
      processes in the progression of associated pathologies. Here we will review this
      important aspect of H. pylori infection. 

PMID- 25945327
TI  - Educational effectiveness, target, and content for prudent antibiotic use.
AB  - Widespread antimicrobial use and concomitant resistance have led to a significant
      threat to public health. Because inappropriate use and overuse of antibiotics
      based on insufficient knowledge are one of the major drivers of antibiotic
      resistance, education about prudent antibiotic use aimed at both the prescribers
      and the public is important. This review investigates recent studies on the
      effect of interventions for promoting prudent antibiotics prescribing. Up to now,
      most educational efforts have been targeted to medical professionals, and many
      studies showed that these educational efforts are significantly effective in
      reducing antibiotic prescribing. Recently, the development of educational
      programs to reduce antibiotic use is expanding into other groups, such as the
      adult public and children. The investigation of the contents of educational
      programs for prescribers and the public demonstrates that it is important to
      develop effective educational programs suitable for each group. In particular, it
      seems now to be crucial to develop appropriate curricula for teaching medical and
      nonmedical (pharmacy, dentistry, nursing, veterinary medicine, and midwifery)
      undergraduate students about general medicine, microbial virulence, mechanism of
      antibiotic resistance, and judicious antibiotic prescribing. 

PMID- 25945328
TI  - Comparison of Intravoxel Incoherent Motion Diffusion-Weighted MR Imaging and
      Arterial Spin Labeling MR Imaging in Gliomas.
AB  - Gliomas grading is important for treatment plan; we aimed to investigate the
      application of intravoxel incoherent motion (IVIM) diffusion-weighted imaging
      (DWI) in gliomas grading, by comparing with the three-dimensional
      pseudocontinuous arterial spin labeling (3D pCASL). 24 patients (13 high grade
      gliomas and 11 low grade gliomas) underwent IVIM DWI and 3D pCASL imaging before
      operation; maps of fast diffusion coefficient (D (*)), slow diffusion coefficient
      (D), fractional perfusion-related volume (f), and apparent diffusion coefficient
      (ADC) as well as cerebral blood flow (CBF) were calculated and then coregistered
      to generate the corresponding parameter values. We found CBF and D (*) were
      higher in the high grade gliomas, whereas ADC, D, and f were lower (all P <
      0.05). In differentiating the high from low grade gliomas, the maximum areas
      under the curves (AUC) of D (*), CBF, and ADC were 0.857, 0.85, and 0.902,
      respectively. CBF was negatively correlated with f in tumor (r = -0.619, P =
      0.001). ADC was positively correlated with D in both tumor and white matter (r =
      0.887, P = 0.000 and r = 0.824, P = 0.000, resp.). There was no correlation
      between CBF and D (*) in both tumor and white matter (P > 0.05). IVIM DWI showed
      more efficiency than 3D pCASL but less validity than conventional DWI in
      differentiating the high from low grade gliomas. 

PMID- 25945329
TI  - Evaluation of the Ribosomal Protein S1 Gene (rpsA) as a Novel Biomarker for
      Mycobacterium Species Identification.
AB  - OBJECTIVES: To evaluate the resolution and reliability of the rpsA gene, encoding
      ribosomal protein S1, as a novel biomarker for mycobacteria species
      identification. METHODS: A segment of the rpsA gene (565 bp) was amplified by PCR
      from 42 mycobacterial reference strains, 172 nontuberculosis mycobacteria
      clinical isolates, and 16 M. tuberculosis complex clinical isolates. The PCR
      products were sequenced and aligned by using the multiple alignment algorithm in
      the MegAlign package (DNASTAR) and the MEGA program. A phylogenetic tree was
      constructed by the neighbor-joining method. RESULTS: Comparative sequence
      analysis of the rpsA gene provided the basis for species differentiation within
      the genus Mycobacterium. Slow- and rapid-growing groups of mycobacteria were
      clearly separated, and each mycobacterial species was differentiated as a
      distinct entity in the phylogenetic tree. The sequences discrepancy was obvious
      between M. kansasii and M. gastri, M. chelonae and M. abscessus, M. avium and M.
      intracellulare, and M. szulgai and M. malmoense, which cannot be achieved by 16S
      ribosomal DNA (rDNA) homologue genes comparison. 183 of the 188 (97.3%) clinical
      isolates, consisting of 8 mycobacterial species, were identified correctly by
      rpsA gene blast. CONCLUSIONS: Our study indicates that rpsA sequencing can be
      used effectively for mycobacteria species identification as a supplement to 16S
      rDNA sequence analysis.

PMID- 25945330
TI  - Understanding the Correlation between Tomographic and Biomechanical Severity of
      Keratoconic Corneas.
AB  - Purpose. To evaluate correlation between tomographic gradation of keratoconus
      (KC) and its corresponding air-puff induced biomechanical response. Methods.
      Corneal tomography and biomechanics were measured with Scheimpflug imaging in 44
      normal and 92 KC corneas. Deformation waveform was also analyzed with Fourier
      series. A custom KC severity scale was used from 1 to 3 with 3 as the most severe
      grade. Tomographic and biomechanical variables were assessed among the grades.
      Sensitivity and specificity of the variables were assessed using receiver
      operating characteristics (ROC). Results. Curvature variables were significantly
      different between normal and disease (P < 0.05) and among grades (P < 0.05).
      Biomechanical variables were significantly different between normal and disease
      (P<0.05) but similar among grades 1 and 2 (P > 0.05). All variables had an area
      under the ROC curve greater than 0.5. The root mean square of the Fourier cosine
      coefficients had the best ROC (0.92, cut-off: 0.027, sensitivity: 83%,
      specificity: 88.6%). Spearman correlation coefficient was significant between
      most variables (P < 0.05). However, tomographic segregation of keratoconus did
      not result in concomitant biomechanical segregation of the grades. Conclusions.
      There was lack of significant biomechanical difference between mild disease
      grades, despite progressive corneal thinning. Mathematical models that estimate
      corneal modulus from air-puff deformation may be more useful. 

PMID- 25945331
TI  - Comment on "Helicobacter pylori Outer Membrane Protein 18 (Hp1125) Is Involved in
      Persistent Colonization by Evading Interferon- gamma Signaling".

PMID- 25945332
TI  - Regulation of Osteoblast Differentiation by Acid-Etched and/or Grit-Blasted
      Titanium Substrate Topography Is Enhanced by 1,25(OH)2D3 in a Sex-Dependent
      Manner.
AB  - This study assessed contributions of micron-scale topography on clinically
      relevant titanium (Ti) to differentiation of osteoprogenitor cells and
      osteoblasts; the interaction of this effect with 1alpha,25-dihydroxyvitamin D3
      (1alpha,25(OH)2D3); and if the effects are sex-dependent. Male and female rat
      bone marrow cells (BMCs) were cultured on acid-etched (A, R a = 0.87 MUm), grit
      blasted (GB, R a = 3.90 MUm), or grit-blasted/acid-etched (SLA, R a = 3.22 MUm)
      Ti. BMCs were sensitive to surface topography and underwent osteoblast
      differentiation. This was greatest on SLA; acid etching and grit blasting
      contributed additively. Primary osteoblasts were also sensitive to SLA, with less
      effect from individual structural components, demonstrated by enhanced local
      factor production. Sex-dependent responses of BMCs to topography varied with
      parameter whereas male and female osteoblasts responded similarly to surface
      treatment. 1alpha,25(OH)2D3 enhanced cell responses on all surfaces similarly.
      Effects were sex-dependent and male cells grown on a complex microstructured
      surface were much more sensitive than female cells. These results indicate that
      effects of the complex SLA topography are greater than acid etching or grit
      blasting alone on multipotent BMCs and committed osteoblasts and that individual
      parameters are sex-specific. The effect of 1alpha,25(OH)2D3 was sex dependent.
      The results also suggest that levels of 1alpha,25(OH)2D3 in the patient may be
      important in osseointegration. 

PMID- 25945333
TI  - Proposal of a Screening MIRU-VNTR Panel for the Preliminary Genotyping of
      Mycobacterium bovis in Mexico.
AB  - Mycobacterium bovis is the major causative agent of bovine tuberculosis, one of
      the most relevant zoonoses in the world, and affects a wide range of wild and
      domesticated animals. Development of screening panels in mycobacterial
      genotyping, according to specific geographical regions, is strongly needed. The
      aim of this study is to select a panel, constituted by highly polymorphic MIRU
      VNTR loci, to discriminate clinical isolates of M. bovis in Mexico. In this
      study, 65 isolates of M. bovis obtained from clinical bovine samples proceeding
      from different geographic regions of Mexico were identified by phenotypic and
      genotypic tests and subsequently genotyped by a 24-locus MIRU-VNTR panel. The
      most polymorphic loci were selected to build a panel with a high discriminatory
      power similar to the 24-locus panel results. A panel of seven elements (QUB 11a,
      MIRU 26, ETR-A, QUB 26, MIRU 16, MIRU 27, and MIRU 39) with the highest allelic
      diversity showed an appropriate differentiation. The selected MIRU-VNTR elements,
      according to the regional allelic variability, may be used in the preliminary
      genotyping of Mycobacterium bovis isolates in Mexico. 

PMID- 25945335
TI  - Transcriptome and Proteome Expression Analysis of the Metabolism of Amino Acids
      by the Fungus Aspergillus oryzae in Fermented Soy Sauce.
AB  - Amino acids comprise the majority of the flavor compounds in soy sauce. A portion
      of these amino acids are formed from the biosynthesis and metabolism of the
      fungus Aspergillus oryzae; however, the metabolic pathways leading to the
      formation of these amino acids in A. oryzae remain largely unknown. We sequenced
      the transcriptomes of A. oryzae 100-8 and A. oryzae 3.042 under similar soy sauce
      fermentation conditions. 2D gel electrophoresis was also used to find some
      differences in protein expression. We found that many amino acid hydrolases
      (endopeptidases, aminopeptidases, and X-pro-dipeptidyl aminopeptidase) were
      expressed at much higher levels (mostly greater than double) in A. oryzae 100-8
      than in A. oryzae 3.042. Our results indicated that glutamate dehydrogenase may
      activate the metabolism of amino acids. We also found that the expression levels
      of some genes changed simultaneously in the metabolic pathways of tyrosine and
      leucine and that these conserved genes may modulate the function of the metabolic
      pathway. Such variation in the metabolic pathways of amino acids is important as
      it can significantly alter the flavor of fermented soy sauce. 

PMID- 25945334
TI  - Experimental protoporphyria: effect of bile acids on liver damage induced by
      griseofulvin.
AB  - The effect of bile acids administration to an experimental mice model of
      Protoporphyria produced by griseofulvin (Gris) was investigated. The aim was to
      assess whether porphyrin excretion could be accelerated by bile acids treatment
      in an attempt to diminish liver damage induced by Gris. Liver damage markers,
      heme metabolism, and oxidative stress parameters were analyzed in mice treated
      with Gris and deoxycholic (DXA), dehydrocholic (DHA), chenodeoxycholic, or
      ursodeoxycholic (URSO). The administration of Gris alone increased the activities
      of glutathione reductase (GRed), superoxide dismutase (SOD), alkaline phosphatase
      (AP), gamma glutamyl transpeptidase (GGT), and glutathione-S-transferase (GST),
      as well as total porphyrins, glutathione (GSH), and cytochrome P450 (CYP) levels
      in liver. Among the bile acids studied, DXA and DHA increased PROTO IX excretion,
      DXA also abolished the action of Gris, reducing lipid peroxidation and hepatic
      GSH and CYP levels, and the activities of GGT, AP, SOD, and GST returned to
      control values. However, porphyrin accumulation was not prevented by URSO;
      instead this bile acid reduced ALA-S and the antioxidant defense enzymes system
      activities. In conclusion, we postulate that DXA acid would be more effective to
      prevent liver damage induced by Gris. 

PMID- 25945336
TI  - Seroprevalence and Risk Factors of Chlamydia Infection in Domestic Rabbits
      (Oryctolagus cuniculus) in China.
AB  - Chlamydia spp. are obligate intracellular bacteria distributed all over the
      world, known to cause various forms of diseases in animals and humans. In the
      present study, a serological survey was conducted to detect the seroprevalence
      and risk factors associated with rabbit chlamydiosis in northeast China,
      including Liaoning province, Jilin province, Heilongjiang province, and Inner
      Mongolia Autonomous Region. Antibodies to Chlamydia were determined by indirect
      hemagglutination assay (IHA). The overall seroprevalence was estimated at 17.88%
      in total of 800 blood samples. The Chlamydia seroprevalence varied in domestic
      rabbits from different factors, and genders of domestic rabbits were considered
      as major risk factors associated with Chlamydia infection. Our study revealed a
      widespread and high prevalence of Chlamydia infection in domestic rabbits in
      northeast China, with higher exposure risk in female domestic rabbits. These
      findings suggested the potential importance of domestic rabbits in the
      transmission of zoonotic Chlamydia infection, and thus Chlamydia should be taken
      into consideration in diagnosing rabbit diseases. To our knowledge, there is no
      report of Chlamydia infection in domestic rabbits in China and the results extend
      the host range for Chlamydia, which has important implications for public health
      and the local economy. 

PMID- 25945337
TI  - Preventive effect of liothyronine on electroconvulsive therapy-induced memory
      deficit in patients with major depressive disorder: a double-blind controlled
      clinical trial.
AB  - Introduction and Objective. Despite the effectiveness of electroconvulsive
      therapy (ECT) in treating major depressive disorder (MDD), its cognitive side
      effects make it less popular. This study investigated the impact of liothyronine
      on ECT-induced memory deficit in patients with MDD. Methodology. This is a double
      blind clinical trial, in which 60 patients with MDD who were referred for ECT
      were selected. The diagnosis was based on the criteria of DSM-IV-TR. Patients
      were divided randomly into two groups to receive either liothyronine (50 mcg
      every morning) or placebo. After the assessment with Wechsler Memory Scale
      Revised (WMS-R) before first session of ECT, posttests were repeated again, two
      months after the completion of ECT. Findings. By controlling the pretest scores,
      the mean scores of the experimental group were higher than the control group in
      delayed recall, verbal memory, visual memory, general memory, and
      attention/concentration scales (P < 0.05). Conclusion. Liothyronine may prevent
      ECT-induced memory impairment in patients with MDD. This study has been
      registered in IRCT under IRCT201401122660N2. 

PMID- 25945339
TI  - Intraoperative Optical Coherence Tomography Using the RESCAN 700: Preliminary
      Results in Collagen Crosslinking.
AB  - PURPOSE: To compare the penetration of riboflavin using a microscope-integrated
      real time spectral domain optical coherence tomography (ZEISS OPMI LUMERA 700 and
      ZEISS RESCAN 700) in keratoconus patients undergoing accelerated collagen
      crosslinking (ACXL) between epithelium on (epi-on) and epithelium off (epi-off).
      METHODS: Intraoperative images were obtained during each of the procedures. Seven
      keratoconus patients underwent epi-on ACXL and four underwent epi-off ACXL. A
      software tool was developed using Microsoft.NET and Open Computer Vision (OpenCV)
      libraries for image analysis. Pre- and postprocedure images were analyzed for
      changes in the corneal hyperreflectance pattern as a measure of the depth of
      riboflavin penetration. RESULTS: The mean corneal hyperreflectance in the epi-on
      group was 12.97 +/- 1.49 gray scale units (GSU) before instillation of riboflavin
      and 14.46 +/- 2.09 GSU after AXCL (P = 0.019) while in the epi-off group it was
      11.43 +/- 2.68 GSU and 16.98 +/- 8.49 GSU, respectively (P = 0.002). The average
      depth of the band of hyperreflectance in the epi-on group was 149.39 +/- 15.63
      microns and in the epi-off group it was 191.04 +/- 32.18 microns. CONCLUSION:
      This novel in vivo, real time imaging study demonstrates riboflavin penetration
      during epi-on and epi-off ACXL.

PMID- 25945338
TI  - Helicobacter pylori Outer Membrane Protein 18 (Hp1125) Is Involved in Persistent
      Colonization by Evading Interferon- gamma Signaling.
AB  - Outer membrane proteins (OMPs) can induce an immune response. Omp18 (HP1125) of
      H. pylori is a powerful antigen that can induce significant interferon-gamma (IFN
      gamma) levels. Previous studies have suggested that IFN-gamma plays an important
      role in H. pylori clearance. However, H. pylori has multiple mechanisms to avoid
      host immune surveillance for persistent colonization. We generated an omp18
      mutant (H. pylori 26695 and H. pylori SS1) strain to examine whether Omp18
      interacts with IFN-gamma and is involved in H. pylori colonization. qRT-PCR
      revealed that IFN-gamma induced Omp18 expression. qRT-PCR and western blot
      analysis revealed reduced expressions of virulence factors CagA and NapA in H.
      pylori 26695 with IFN-gamma treatment, but they were induced in the Deltaomp18
      strain. In C57BL/6 mice infected with H. pylori SS1 and the Deltaomp18 strain,
      the Deltaomp18 strain conferred defective colonization and activated a stronger
      inflammatory response. Signal transducer phosphorylation and transcription 1
      (STAT1) activator was downregulated by the wild-type strain but not the
      Deltaomp18 strain in IFN-gamma-treated macrophages. Furthermore, Deltaomp18
      strain survival rates were poor in macrophages compared to the wild-type strain.
      We concluded that H. pylori Omp18 has an important function influencing IFN-gamma
      mediated immune response to participate in persistent colonization. 

PMID- 25945340
TI  - Sulfated Polysaccharides Isolated from Cloned Grateloupia filicina and Their
      Anticoagulant Activity.
AB  - Sulfated polysaccharides (GSP) were isolated from the cloned Grateloupia filicina
      which was cultured in Jiaozhou Bay, Qingdao, China. The yield of GSP was 15.75%.
      The total sugar and sulfate were 40.90 and 19.89%, respectively. And the average
      molecular weight was 11.7 KDa. The results of neutral sugar analysis showed that
      GSP was mainly sulfated polysaccharides of galactose. The experiments for
      activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin
      time (TT) anticoagulant assays in vitro indicated that GSP was a good potential
      anticoagulant. Therefore, this study supplied new thought for the cloned
      Grateloupia filicina exploitation of high-value products.

PMID- 25945341
TI  - Shaped singular spectrum analysis for quantifying gene expression, with
      application to the early Drosophila embryo.
AB  - In recent years, with the development of automated microscopy technologies, the
      volume and complexity of image data on gene expression have increased
      tremendously. The only way to analyze quantitatively and comprehensively such
      biological data is by developing and applying new sophisticated mathematical
      approaches. Here, we present extensions of 2D singular spectrum analysis (2D-SSA)
      for application to 2D and 3D datasets of embryo images. These extensions,
      circular and shaped 2D-SSA, are applied to gene expression in the nuclear layer
      just under the surface of the Drosophila (fruit fly) embryo. We consider the
      commonly used cylindrical projection of the ellipsoidal Drosophila embryo. We
      demonstrate how circular and shaped versions of 2D-SSA help to decompose
      expression data into identifiable components (such as trend and noise), as well
      as separating signals from different genes. Detection and improvement of under-
      and overcorrection in multichannel imaging is addressed, as well as the
      extraction and analysis of 3D features in 3D gene expression patterns. 

PMID- 25945343
TI  - Nordihydroguaiaretic Acid Disrupts the Antioxidant Ability of Helicobacter pylori
      through the Repression of SodB Activity In Vitro.
AB  - Iron-cofactored superoxide dismutase (SodB) of Helicobacter pylori plays an
      indispensable role in the bacterium's colonization of the stomach. Previously, we
      demonstrated that FecA1, a Fe(3+)-dicitrate transporter homolog, contributes to
      SodB activation by supplying ferrous iron (Fe(2+)) to SodB, and fecA1-deletion
      mutant strains have reduced gastric mucosal-colonization ability in Mongolian
      gerbils, suggesting that FecA1 is a possible target for the development of a
      novel eradication therapy. This study aimed to identify novel FecA1-binding
      compounds in silico and then examined the effect of a predicted FecA1-binding
      compound on H. pylori SodB activity in vitro. Specifically, we demonstrated that
      nordihydroguaiaretic acid (NDGA) is a predicted FecA1-binding compound. NDGA
      reduced intracellular Fe(2+) levels in H. pylori and reduced SodB activity.
      Additionally, NDGA increased H2O2 sensitivity of H. pylori and increased the
      metronidazole (Mtz) sensitivity. The present study demonstrated that NDGA
      repressed SodB activity associated with the gastric mucosal-colonization via
      inhibition of intracellular Fe(2+) uptake by FecA1, suggesting that NDGA might be
      effective for the development of a novel eradication therapy. 

PMID- 25945342
TI  - beta-Catenin-Dependent Signaling Pathway Contributes to Renal Fibrosis in
      Hypertensive Rats.
AB  - The mechanism of hypertension-induced renal fibrosis is not well understood,
      although it is established that high levels of angiotensin II contribute to the
      effect. Since beta-catenin signal transduction participates in fibrotic
      processes, we evaluated the contribution of beta-catenin-dependent signaling
      pathway in hypertension-induced renal fibrosis. Two-kidney one-clip (2K1C)
      hypertensive rats were treated with lisinopril (10 mg/kg/day for four weeks) or
      with pyrvinium pamoate (Wnt signaling inhibitor, single dose of 60 ug/kg, every 3
      days for 2 weeks). The treatment with lisinopril reduced the systolic blood
      pressure from 220 +/- 4 in 2K1C rats to 112 +/- 5 mmHg (P < 0.05), whereas the
      reduction in blood pressure with pyrvinium pamoate was not significant (212 +/- 6
      in 2K1C rats to 170 +/- 3 mmHg, P > 0.05). The levels of collagen types I and
      III, osteopontin, and fibronectin decreased in the unclipped kidney in both
      treatments compared with 2K1C rats. The expressions of beta-catenin, p-Ser9-GSK
      3beta, and the beta-catenin target genes cyclin D1, c-myc, and bcl-2
      significantly decreased in unclipped kidney in both treatments (P < 0.05). In
      this study we provided evidence that beta-catenin-dependent signaling pathway
      participates in the renal fibrosis induced in 2K1C rats.

PMID- 25945344
TI  - Prevalence of Helicobacter pylori vacA, cagA, and iceA Genotypes in Cuban
      Patients with Upper Gastrointestinal Diseases.
AB  - Virulence factors of Helicobacter pylori can predict the development of different
      gastroduodenal diseases. There are scarce reports in Cuba about H. pylori
      isolates genotyping. The aim of the present investigation was to identify allelic
      variation of the virulence genes vacA, cagA, and iceA in sixty-eight patients
      diagnosed as H. pylori positive by culture. In seven out of 68 patients, strains
      from both gastric regions were obtained and considered independent. DNA was
      extracted from all the H. pylori strains and evaluated by PCR-genotyping. The
      vacA s1 allele, cagA gene, and iceA2 allele were the most prevalent (72.0%,
      56.0%, and 57.3%, respectively). Alleles from m-region showed a similar frequency
      as s1a and s1b subtypes. The presence of multiple H. pylori genotypes in a single
      biopsy and two gastric region specimens were found. Significant statistical
      association was observed between iceA2 allele and patients with non-peptic ulcer
      dyspepsia (NUD) (P = 0.037) as well as virulence genotypes (s1, s1m2) and
      patients over 40 years old (P < 0.05). In conclusion, the results demonstrated a
      high prevalence of H. pylori virulent genotypes in Cuban patients over 40 years
      old while iceA2 alleles demonstrated a good specificity in patients with NUD. 

PMID- 25945345
TI  - Metabolic Engineering of Escherichia coli for Poly(3-hydroxybutyrate) Production
      under Microaerobic Condition.
AB  - The alcohol dehydrogenase promoter PadhE and mixed acid fermentation pathway
      deficient mutants of Escherichia coli were employed to produce poly(3
      hydroxybutyrate) (P3HB) under microaerobic condition. The E. coli mutant with
      ackA-pta, poxB, ldhA, and adhE deletions accumulated 0.67 g/L P3HB, up to 78.84%
      of cell dry weight in tube cultivation. The deletion of pyruvate formate-lyase
      gene pflB drastically decreased P3HB production and P3HB content to 0.09 g/L and
      24.44%, respectively. Overexpressing pflB via the plasmid in its knocked out
      mutant restored cell growth and P3HB accumulation, indicating the importance of
      the pyruvate formate-lyase in microaerobic carbon metabolism. The engineered E.
      coli BWapld (pWYC09) produced 5.00 g/L P3HB from 16.50 g/L glucose in 24 h batch
      fermentation, and P3HB production yield from glucose was 0.30 g/g, which reached
      up to 63% of maximal theoretical yield. 

PMID- 25945346
TI  - Gastric Carcinogenesis and Underlying Molecular Mechanisms: Helicobacter pylori
      and Novel Targeted Therapy.
AB  - The oxygen-derived free radicals that are released from activated neutrophils are
      one of the cytotoxic factors of Helicobacter pylori-induced gastric mucosal
      injury. Increased cytidine deaminase activity in H. pylori-infected gastric
      tissues promotes the accumulation of various mutations and might promote gastric
      carcinogenesis. Cytotoxin-associated gene A (CagA) is delivered into gastric
      epithelial cells via bacterial type IV secretion system, and it causes
      inflammation and activation of oncogenic pathways. H. pylori infection induces
      epigenetic transformations, such as aberrant promoter methylation in tumor
      suppressor genes. Aberrant expression of microRNAs is also reportedly linked to
      gastric tumorogenesis. Moreover, recent advances in molecular targeting therapies
      provided a new interesting weapon to treat advanced gastric cancer through anti
      human epidermal growth factor receptor 2 (HER-2) therapies. This updated review
      article highlights possible mechanisms of gastric carcinogenesis including H.
      pylori-associated factors. 

PMID- 25945347
TI  - The role of vaspin in the development of metabolic and glucose tolerance
      disorders and atherosclerosis.
AB  - In recent years, most research efforts have been focused on studying insulin
      sensitizing adipokines. One of the most recently discovered adipokines is vaspin,
      a visceral adipose tissue-derived serine protease inhibitor. Vaspin levels have
      been found significantly increased in mice with obesity and insulin resistance.
      It has been assumed that vaspin serves as an insulin sensitizer with anti
      inflammatory effects and might act as a compensatory mechanism in response to
      decreased insulin sensitivity. Most studies in humans have shown a positive
      correlation between vaspin gene expression and serum levels, and metabolic
      syndrome parameters. Vaspin gene expression is influenced by age and gender, and
      the administration of insulin sensitizers enhances it in mice, whereas the use of
      metformin decreases serum vaspin levels in humans, probably due to different
      regulatory mechanisms. Presumably vaspin plays local and endocrine role in the
      development of initial and advanced atherosclerosis in obese subjects and might
      be used as a predictor of coronary and cerebrovascular disease. It is believed
      that vaspin could be regarded as a new link between obesity and related metabolic
      disorders, including glucose intolerance. The entire understanding of vaspin
      intimate mechanism of action might enable the development of novel etiology-based
      treatment strategies, targeting metabolic and glucose tolerance disorders. 

PMID- 25945348
TI  - Genetic polymorphism in extracellular regulators of Wnt signaling pathway.
AB  - The Wnt signaling pathway is mediated by a family of secreted glycoproteins
      through canonical and noncanonical mechanism. The signaling pathways are
      regulated by various modulators, which are classified into two classes on the
      basis of their interaction with either Wnt or its receptors. Secreted frizzled
      related proteins (sFRPs) are the member of class that binds to Wnt protein and
      antagonizes Wnt signaling pathway. The other class consists of Dickkopf (DKK)
      proteins family that binds to Wnt receptor complex. The present review discusses
      the disease related association of various polymorphisms in Wnt signaling
      modulators. Furthermore, this review also highlights that some of the sFRPs and
      DKKs are unable to act as an antagonist for Wnt signaling pathway and thus their
      function needs to be explored more extensively. 

PMID- 25945349
TI  - Evaluation of Candida Colonization and Specific Humoral Responses against Candida
      albicans in Patients with Atopic Dermatitis.
AB  - The aim of this study was to assess the candidal colonization and specific
      humoral responses against Candida albicans in patients with atopic dermatitis.
      One hundred patients with atopic dermatitis and 50 healthy individuals were
      enrolled in the study. Skin and oral specimens from all participants were
      cultured on CHROMagar Candida medium. Isolated yeasts were identified by using
      the sequence of the D1/D2 domain of the 26S rRNA gene. ELISA was used for
      detection of IgM, IgA, and IgG antibodies against C. albicans in sera of
      participants. Candida species were isolated from the skin and oral cavity of 31%
      of the patients and 12% of the controls. There was no significant difference
      between Candida colonization in patients and controls (P > 0.05). Candida
      albicans was isolated from the skin and oral cavity of 23% of the patients and 6%
      of the controls (P < 0.05). There were no significant differences between serum
      levels of IgM and IgA in patients and controls (P > 0.05). Serum level of IgG was
      significantly lower in patients than in controls (P < 0.05). Type of Candida
      colonization can change in patients with atopic dermatitis. In addition, these
      patients have abnormalities in the production of antibodies against Candida
      albicans that may have a role in the pathogenesis of atopic dermatitis.

PMID- 25945351
TI  - Comparative Evaluation of Different Test Combinations for Diagnosis of
      Mycobacterium avium Subspecies paratuberculosis Infecting Dairy Herds in India.
AB  - A total of 355 cows were sampled (serum, n = 315; faeces, n = 355; milk, n = 209)
      from dairy farms located in the Punjab state of India. Faeces and serum/milk
      samples were screened by acid fast staining and "indigenous ELISA," respectively.
      IS900 PCR was used to screen faeces and milk samples. Bio-load of MAP in dairy
      cows was 36.9, 15.6, 16.3, and 14.4%, using microscopy, serum ELISA, milk ELISA
      and milk PCR, respectively. Estimated kappa values between different test
      combinations: serum and milk ELISA, faecal microscopy and faecal PCR, milk ELISA
      and milk PCR, faecal PCR and serum ELISA were 0.325, 0.241, 0.682, and 0.677,
      respectively. Estimation of the relative sensitivity and specificity of different
      tests in the present study indicated that "serum ELISA" and "milk ELISA" were
      good screening tests, add "milk PCR" was "confirmatory test" for MAP infection.
      Combination of milk ELISA with milk PCR may be adopted as a model strategy for
      screening and diagnosis of JD in lactating/dairy cattle herds in Indian
      conditions. 

PMID- 25945350
TI  - Variants of SCARB1 and VDR Involved in Complex Genetic Interactions May Be
      Implicated in the Genetic Susceptibility to Clear Cell Renal Cell Carcinoma.
AB  - The current data are still inconclusive in terms of a genetic component involved
      in the susceptibility to renal cell carcinoma. Our aim was to evaluate 40
      selected candidate polymorphisms for potential association with clear cell renal
      cell carcinoma (ccRCC) based on independent group of 167 patients and 200 healthy
      controls. The obtained data were searched for independent effects of particular
      polymorphisms as well as haplotypes and genetic interactions. Association testing
      implied position rs4765623 in the SCARB1 gene (OR = 1.688, 95% CI: 1.104-2.582, P
      = 0.016) and a haplotype in VDR comprising positions rs739837, rs731236,
      rs7975232, and rs1544410 (P = 0.012) to be the risk factors in the studied
      population. The study detected several epistatic effects contributing to the
      genetic susceptibility to ccRCC. Variation in GNAS1 was implicated in a strong
      synergistic interaction with BIRC5. This effect was part of a model suggested by
      multifactor dimensionality reduction method including also a synergy between
      GNAS1 and SCARB1 (P = 0.036). Significance of GNAS1-SCARB1 interaction was
      further confirmed by logistic regression (P = 0.041), which also indicated
      involvement of SCARB1 in additional interaction with EPAS1 (P = 0.008) as well as
      revealing interactions between GNAS1 and EPAS1 (P = 0.016), GNAS1 and MC1R (P =
      0.031), GNAS1 and VDR (P = 0.032), and MC1R and VDR (P = 0.035). 

PMID- 25945352
TI  - Therapeutic Benefit of Extended Thymosin beta4 Treatment Is Independent of Blood
      Glucose Level in Mice with Diabetic Peripheral Neuropathy.
AB  - Peripheral neuropathy is a chronic complication of diabetes mellitus. To
      investigated the efficacy and safety of the extended treatment of diabetic
      peripheral neuropathy with thymosin beta4 (Tbeta4), male diabetic mice (db/db) at
      the age of 24 weeks were treated with Tbeta4 or saline for 16 consecutive weeks.
      Treatment of diabetic mice with Tbeta4 significantly improved motor (MCV) and
      sensory (SCV) conduction velocity in the sciatic nerve and the thermal and
      mechanical latency. However, Tbeta4 treatment did not significantly alter blood
      glucose levels. Treatment with Tbeta4 significantly increased intraepidermal
      nerve fiber density. Furthermore, Tbeta4 counteracted the diabetes-induced axon
      diameter and myelin thickness reductions and the g-ratio increase in sciatic
      nerve. In vitro, compared with dorsal root ganglia (DRG) neurons derived from
      nondiabetic mice, DRG neurons derived from diabetic mice exhibited significantly
      decreased neurite outgrowth, whereas Tbeta4 promoted neurite growth in these
      diabetic DRG neurons. Blockage of the Ang1/Tie2 signaling pathway with a
      neutralized antibody against Tie2 abolished Tbeta4-increased neurite outgrowth.
      Our data demonstrate that extended Tbeta4 treatment ameliorates diabetic-induced
      axonal degeneration and demyelination, which likely contribute to therapeutic
      effect of Tbeta4 on diabetic neuropathy. The Ang1/Tie2 pathway may mediate Tbeta4
      induced axonal remodeling. 

PMID- 25945353
TI  - New-onset diabetes and glucose regulation are significant determinants of left
      ventricular hypertrophy in renal transplant recipients.
AB  - BACKGROUND: New-onset diabetes after transplantation (NODAT) is associated with
      decreased graft survival and an increased risk for cardiovascular disease. The
      objective of this study was to evaluate the risk factors for development of NODAT
      and its' relationship with arterial stiffness and left ventricular mass index
      (LVMI) in kidney transplant recipients. METHODS: 159 kidney transplant recipients
      were selected from our transplantation center who underwent renal transplantation
      between years 2007 and 2010. RESULTS: Among 159 patients, 57 (32.2%) patients
      were with NODAT who were significantly older than patients without diabetes (P:
      0.0001). Patients with NODAT had significantly higher pulse wave velocity (PWv)
      (P: 0.033) and left ventricular mass index LVMI (P: 0.001) compared to patients
      without NODAT. Further analysis was done according to LVMI as follows: LVMI > 130
      g/m(2) (n: 57) and LVMI <= 130 g/m(2) (n: 102). We observed higher office
      systolic and diastolic BP, serum trygliceride, glucose, creatinine, age, and
      HbA1c (P: 0.0001) levels in patients with LVMI > 130 g/m(2). Linear regression
      analysis revealed that HbA1c was the major determinant of LVMI (P: 0.026, beta:
      0.361). CONCLUSIONS: HbA1c is the major determinant of LVMI, so strict control of
      serum glucose levels is essential for preventing cardiovascular disease in
      patients with NODAT.

PMID- 25945354
TI  - Diabetic retinopathy in pregnancy: a population-based study of women with
      pregestational diabetes.
AB  - The aim of this observational study was to evaluate screening and progression of
      diabetic retinopathy during pregnancy in women with pregestational diabetes
      attending five antenatal centres along the Irish Atlantic seaboard. An adequate
      frequency of screening was defined as at least two retinal evaluations in
      separate trimesters. Progression was defined as at least one stage of
      deterioration of diabetic retinopathy and/or development of diabetic macular
      edema on at least one eye. Women with pregestational diabetes who delivered after
      22 gestational weeks (n = 307) were included. In total, 185 (60.3%) had an
      adequate number of retinal examinations. Attendance at prepregnancy care was
      associated with receiving adequate screening (odds ratio 6.23; CI 3.39-11.46 (P <
      0.001)). Among those who received adequate evaluations (n = 185), 48 (25.9%) had
      retinopathy progression. Increasing booking systolic blood pressure (OR 1.03, CI
      1.01-1.06, P = 0.02) and greater drop in HbA1c between first and third trimesters
      of pregnancy (OR 2.05, CI 1.09-3.87, P = 0.03) significantly increased the odds
      of progression. A significant proportion of women continue to demonstrate
      retinopathy progression during pregnancy. This study highlights the role of
      prepregnancy care and the importance of close monitoring during pregnancy and
      identifies those patients at the highest risk for retinopathy progression. 

PMID- 25945355
TI  - A new approach to define and diagnose cardiometabolic disorder in children.
AB  - The aim of the study was to test the performance of a new definition of metabolic
      syndrome (MetS), which better describes metabolic dysfunction in children.
      Methods. 15,794 youths aged 6-18 years participated. Mean z-score for CVD risk
      factors was calculated. Sensitivity analyses were performed to evaluate which
      parameters best described the metabolic dysfunction by analysing the score
      against independent variables not included in the score. Results. More youth had
      clustering of CVD risk factors (>6.2%) compared to the number selected by
      existing MetS definitions (International Diabetes Federation (IDF) < 1%). Waist
      circumference and BMI were interchangeable, but using insulin resistance
      homeostasis model assessment (HOMA) instead of fasting glucose increased the
      score. The continuous MetS score was increased when cardiorespiratory fitness
      (CRF) and leptin were included. A mean z-score of 0.40-0.85 indicated borderline
      and above 0.85 indicated clustering of risk factors. A noninvasive risk score
      based on adiposity and CRF showed sensitivity and specificity of 0.85 and an area
      under the curve of 0.92 against IDF definition of MetS. Conclusions. Diagnosis
      for MetS in youth can be improved by using continuous variables for risk factors
      and by including CRF and leptin. 

PMID- 25945356
TI  - Sensitivity and Specificity Improvement in Abdominal Obesity Diagnosis Using
      Cluster Analysis during Waist Circumference Cut-Off Point Selection.
AB  - INTRODUCTION: The purpose of this study was to analyze the influence of metabolic
      phenotypes during the construction of ROC curves for waist circumference (WC)
      cutpoint selection. MATERIALS AND METHODS: A total of 1,902 subjects of both
      genders were selected from the Maracaibo City Metabolic Syndrome Prevalence Study
      database. Two-Step Cluster Analysis (TSCA) was applied to select metabolically
      healthy and sick men and women. ROC curves were constructed to determine WC
      cutoff points by gender. RESULTS: Through TSCA, metabolic phenotype predictive
      variables were selected: HOMA2-IR and HOMA2-betacell for women and HOMA2-IR,
      HOMA2-betacell, and TAG for men. Subjects were classified as healthy normal
      weight, metabolically obese normal weight, healthy and metabolically disturbed
      overweight, and healthy and metabolically disturbed obese. Final WC cutpoints
      were 91.50 cm for women (93.4% sensitivity, 93.7% specificity) and 98.15 cm for
      men (96% sensitivity, 99.5% specificity). CONCLUSIONS: TSCA in the selection of
      the groups used in ROC curves construction proved to be an important tool, aiding
      in the detection of MOWN and MHO which cannot be identified with WC alone. The
      resulting WC cutpoints were <91.00 cm for women and <98.00 cm for men.
      Furthermore, anthropometry is insufficient to determine healthiness, and,
      biochemical analysis is needed to properly filter subjects during classification.

PMID- 25945358
TI  - Manual physical therapists' use of biopsychosocial history taking in the
      management of patients with back or neck pain in clinical practice.
AB  - OBJECTIVE: To develop and evaluate process indicators relevant to biopsychosocial
      history taking in patients with chronic back and neck pain. METHODS: The SCEBS
      method, covering the Somatic, Psychological (Cognition, Emotion, and Behavior),
      and Social dimensions of chronic pain, was used to evaluate biopsychosocial
      history taking by manual physical therapists (MPTs). In Phase I, process
      indicators were developed while in Phase II indicators were tested in practice.
      RESULTS: Literature-based recommendations were transformed into 51 process
      indicators. Twenty MTPs contributed 108 patient audio recordings. History taking
      was excellent (98.3%) for the Somatic dimension, very inadequate for Cognition
      (43.1%) and Behavior (38.3%), weak (27.8%) for Emotion, and low (18.2%) for the
      Social dimension. MTPs estimated their coverage of the Somatic dimension as
      excellent (100%), as adequate for Cognition, Emotion, and Behavior (60.1%), and
      as very inadequate for the Social dimension (39.8%). CONCLUSION: MTPs perform
      screening for musculoskeletal pain mainly through the use of somatic dimension of
      (chronic) pain. Psychological and social dimensions of chronic pain were
      inadequately covered by MPTs. Furthermore, a substantial discrepancy between
      actual and self-estimated use of biopsychosocial history taking was noted. We
      strongly recommend full implementation of the SCEBS method in educational
      programs in manual physical therapy.

PMID- 25945359
TI  - Corrigendum to "A preliminary investigation of user perception and behavioral
      intention for different review types: customers and designers perspective".

PMID- 25945357
TI  - Present and future in the treatment of diabetic kidney disease.
AB  - Diabetic kidney disease is the leading cause of end-stage renal disease.
      Albuminuria is recognized as the most important prognostic factor for chronic
      kidney disease progression. For this reason, blockade of renin-angiotensin system
      remains the main recommended strategy, with either angiotensin converting enzyme
      inhibitors or angiotensin II receptor blockers. However, other antiproteinuric
      treatments have begun to be studied, such as direct renin inhibitors or
      aldosterone blockers. Beyond antiproteinuric treatments, other drugs such as
      pentoxifylline or bardoxolone have yielded conflicting results. Finally,
      alternative pathogenic pathways are being explored, and emerging therapies
      including antifibrotic agents, endothelin receptor antagonists, or transcription
      factors show promising results. The aim of this review is to explain the advances
      in newer agents to treat diabetic kidney disease, along with the background of
      the renin-angiotensin system blockade. 

PMID- 25945361
TI  - The mixed finite element multigrid method for stokes equations.
AB  - The stable finite element discretization of the Stokes problem produces a
      symmetric indefinite system of linear algebraic equations. A variety of iterative
      solvers have been proposed for such systems in an attempt to construct efficient,
      fast, and robust solution techniques. This paper investigates one of such
      iterative solvers, the geometric multigrid solver, to find the approximate
      solution of the indefinite systems. The main ingredient of the multigrid method
      is the choice of an appropriate smoothing strategy. This study considers the
      application of different smoothers and compares their effects in the overall
      performance of the multigrid solver. We study the multigrid method with the
      following smoothers: distributed Gauss Seidel, inexact Uzawa, preconditioned
      MINRES, and Braess-Sarazin type smoothers. A comparative study of the smoothers
      shows that the Braess-Sarazin smoothers enhance good performance of the multigrid
      method. We study the problem in a two-dimensional domain using stable Hood-Taylor
      Q2-Q1 pair of finite rectangular elements. We also give the main theoretical
      convergence results. We present the numerical results to demonstrate the
      efficiency and robustness of the multigrid method and confirm the theoretical
      results.

PMID- 25945360
TI  - Effects in Short and Long Term of Global Postural Reeducation (GPR) on Chronic
      Low Back Pain: A Controlled Study with One-Year Follow-Up.
AB  - OBJECTIVE: Comparing global postural reeducation (GPR) to a standard
      physiotherapy treatment (PT) based on active exercises, stretching, and massaging
      for improving pain and function in chronic low back pain (CLBP) patients. DESIGN:
      Prospective controlled study. Setting. Outpatient rehabilitation facility.
      PARTICIPANTS: Adult patients with diagnosis of nonspecific, chronic (>6 months)
      low back pain. INTERVENTIONS: Both treatments consisted of 15 sessions of one
      hour each, twice a week including patient education. MEASURES: Roland Morris
      Disability Questionnaire to evaluate disability, and Numeric Analog Scale for
      pain. A score change >30% was considered clinically significant. Past treatments,
      use of medications, smoking habits, height, weight, profession, and physical
      activity were also recorded on baseline, on discharge, and 1 year after discharge
      (resp., T0, T1, and T2). RESULTS: At T0 103 patients with cLBP (51 cases and 52
      controls) were recruited. The treatment (T1) has been completed by 79 (T1) of
      which 60 then carried out the 1-year follow-up (T2). Both GPR and PT at T1 were
      associated with a significant statistical and clinical improvement in pain and
      function, compared to T0. At T2, only pain in GPR still registered a
      statistically significant improvement.

PMID- 25945362
TI  - Diagnosing and ranking retinopathy disease level using diabetic fundus image
      recuperation approach.
AB  - Retinal fundus images are widely used in diagnosing different types of eye
      diseases. The existing methods such as Feature Based Macular Edema Detection
      (FMED) and Optimally Adjusted Morphological Operator (OAMO) effectively detected
      the presence of exudation in fundus images and identified the true positive ratio
      of exudates detection, respectively. These mechanically detected exudates did not
      include more detailed feature selection technique to the system for detection of
      diabetic retinopathy. To categorize the exudates, Diabetic Fundus Image
      Recuperation (DFIR) method based on sliding window approach is developed in this
      work to select the features of optic cup in digital retinal fundus images. The
      DFIR feature selection uses collection of sliding windows with varying range to
      obtain the features based on the histogram value using Group Sparsity
      Nonoverlapping Function. Using support vector model in the second phase, the DFIR
      method based on Spiral Basis Function effectively ranks the diabetic retinopathy
      disease level. The ranking of disease level on each candidate set provides a much
      promising result for developing practically automated and assisted diabetic
      retinopathy diagnosis system. Experimental work on digital fundus images using
      the DFIR method performs research on the factors such as sensitivity, ranking
      efficiency, and feature selection time. 

PMID- 25945363
TI  - A novel rules based approach for estimating software birthmark.
AB  - Software birthmark is a unique quality of software to detect software theft.
      Comparing birthmarks of software can tell us whether a program or software is a
      copy of another. Software theft and piracy are rapidly increasing problems of
      copying, stealing, and misusing the software without proper permission, as
      mentioned in the desired license agreement. The estimation of birthmark can play
      a key role in understanding the effectiveness of a birthmark. In this paper, a
      new technique is presented to evaluate and estimate software birthmark based on
      the two most sought-after properties of birthmarks, that is, credibility and
      resilience. For this purpose, the concept of soft computing such as probabilistic
      and fuzzy computing has been taken into account and fuzzy logic is used to
      estimate properties of birthmark. The proposed fuzzy rule based technique is
      validated through a case study and the results show that the technique is
      successful in assessing the specified properties of the birthmark, its resilience
      and credibility. This, in turn, shows how much effort will be required to detect
      the originality of the software based on its birthmark. 

PMID- 25945364
TI  - Development of a portable gait rehabilitation system for home-visit
      rehabilitation.
AB  - This paper describes the development of a gait rehabilitation system with a
      locomotion interface (LI) for home-visit rehabilitation. For this purpose, the LI
      should be compact, small, and easy to move. The LI has two 2 degree-of-freedom
      (DOF) manipulators with footpads to move each foot along a trajectory. When the
      user stands on the footpads, the system can move his or her feet while the body
      remains stationary. The footpads can have various trajectories, which are
      prerecordings of the movements of healthy individuals walking on plane surfaces
      or slopes. The homes of stroke patients may have not only flat surfaces but also
      some slopes and staircases. The quadriceps femoris muscle is important for
      walking up and down slopes and staircases, and the eccentric and concentric
      contractions of this muscle are, in particular, difficult to train under normal
      circumstances. Therefore, we developed a graded-walking program for the system
      used in this study. Using this system, the user can undergo gait rehabilitation
      in their home, during visits by a physical therapist. An evaluation of the
      results of tests showed that the vastus medialis muscles of all the subjects were
      stimulated more than by walking on real slopes. 

PMID- 25945365
TI  - Detection of Prosthetic Knee Movement Phases via In-Socket Sensors: A Feasibility
      Study.
AB  - This paper presents an approach of identifying prosthetic knee movements through
      pattern recognition of mechanical responses at the internal socket's wall. A
      quadrilateral double socket was custom made and instrumented with two force
      sensing resistors (FSR) attached to specific anterior and posterior sites of the
      socket's wall. A second setup was established by attaching three piezoelectric
      sensors at the anterior distal, anterior proximal, and posterior sites. Gait
      cycle and locomotion movements such as stair ascent and sit to stand were adopted
      to characterize the validity of the technique. FSR and piezoelectric outputs were
      measured with reference to the knee angle during each phase. Piezoelectric
      sensors could identify the movement of midswing and terminal swing, pre-full
      standing, pull-up at gait, sit to stand, and stair ascent. In contrast, FSR could
      estimate the gait cycle stance and swing phases and identify the pre-full
      standing at sit to stand. FSR showed less variation during sit to stand and stair
      ascent to sensitively represent the different movement states. The study
      highlighted the capacity of using in-socket sensors for knee movement
      identification. In addition, it validated the efficacy of the system and warrants
      further investigation with more amputee subjects and different sockets types. 

PMID- 25945366
TI  - Discovery and identification of a series of alkyl decalin isomers in petroleum
      geological samples.
AB  - The comprehensive two-dimensional gas chromatography/time-of-flight mass
      spectrometry (GC * GC/TOFMS) has been used to characterize a crude oil and a
      source rock extract sample. During the process, a series of pairwise components
      between monocyclic alkanes and mono-aromatics have been discovered. After
      tentative assignments of decahydronaphthalene isomers, a series of alkyl decalin
      isomers have been synthesized and used for identification and validation of these
      petroleum compounds. From both the MS and chromatography information, these
      pairwise compounds were identified as 2-alkyl-decahydronaphthalenes and 1-alkyl
      decahydronaphthalenes. The polarity of 1-alkyl-decahydronaphthalenes was
      stronger. Their long chain alkyl substituent groups may be due to bacterial
      transformation or different oil cracking events. This systematic profiling of
      alkyl-decahydronaphthalene isomers provides further understanding and recognition
      of these potential petroleum biomarkers. 

PMID- 25945367
TI  - Rheumatic heart disease in Africa: interventions  beyond prevention.

PMID- 25945368
TI  - American Heart Association 2014 late-breaking  clinical trials.

PMID- 25945369
TI  - [Talking about anxiety].

PMID- 25945370
TI  - [A clinical researcher full of energy].

PMID- 25945371
TI  - [Manners in Switzerland].

PMID- 25945372
TI  - [Obituary for Prof. Dr. Herbert Lochs (1946-2015) ].

PMID- 25945374
TI  - [Editorial].

PMID- 25945375
TI  - [Home parenteral nutrition in oncology].

PMID- 25945376
TI  - [Oncology in pictures].

PMID- 25945377
TI  - [Cerebri anatome by T. Willis: the history of the creation and the role in the
      development of the neurology (to the 350th anniversary of the first publication].

PMID- 25945378
TI  - [Role of astrocytes in alterations of glutamatergic neurotransmission in
      schizophrenia].
AB  - The glutamatergic hypothesis of schizophrenia based on the hypofunction of the N
      methyl-D-aspartate-type glutamate receptors (NMDA-R) is one of the most widely
      implicated hypothesis that explains the origin of positive and negative symptoms
      of illness as well as cognitive deficits. The author considered a
      neuromorphological aspect of this hypothesis related to the glial astrocytes
      function. The literature on the astrocyte ability to regulate glutamate
      neurotransmission is reviewed. Astrocyte abnormalities in schizophrenia include
      the disturbances of glutamate reuptake, recycling and turnover of endogenous NMDA
      R ligands. The results of the experimental and clinical studies that target
      levels of endogenous NMDA-R ligands, their enzymes and transporters for treatment
      of schizophrenia symptoms are discussed. Further studies studies are needed to
      develop this strategy.

PMID- 25945379
TI  - Response to letter regarding "differential hemodynamic effects of exercise and
      volume expansion in people with and without heart failure".

PMID- 25945380
TI  - [Pathological deformation of the carotid arteries].
AB  - The literature on the etiology, pathogenesis, clinical manifestations and
      pathology, basic approaches to the treatment of congenital and acquired
      pathological deformation of the internal carotid artery has been analyzed. The
      review discusses the possible risk factors and diseases that lead to the
      development of pathological deformations as well as existing hypotheses of
      pathogenesis. Open and unresolved issues of the etiology and pathogenesis of this
      disease are identified. The disputable issues on the emergence and development of
      vascular deformations in children, young people and elderly are discussed. The
      authors posit a hypothesis that congenital and acquired pathological deformations
      are different diseases which differ by etiology, pathogenesis, clinical and
      pathomorphological picture, prognosis, approaches to diagnosis and treatment; the
      relationship between them has not been proved.

PMID- 25945381
TI  - [Cellular and molecular mechanisms of radiation-induced brain injury: can
      peripheral markers be detected?].
AB  - Investigation of the mechanisms of radiation-induced brain injury is a relevant
      fundamental objective of radiobiology and neuroradiology. Damage to the healthy
      brain tissue is the key factor limiting the application of radiation therapy in
      patients with nervous systems neoplasms. Furthermore, postradiation brain injury
      can be clinically indiscernible from continued tumor growth and requires
      differential diagnosis. Thus, there exists high demand for biomarkers of
      radiation effects on the brain in neurosurgery and radiobiology. These markers
      could be used for better understanding and quantifying the effects of ionizing
      radiation on brain tissues, as well as for elaborating personalized therapy.
      Despite the high demand, biomarkers of radiation-induced brain injury have not
      been identified thus far. The cellular and molecular mechanisms of the effect of
      ionizing radiation on the brain were analyzed in this review in order to identify
      potential biomarkers of radiation-induced injury to nervous tissue.

PMID- 25945382
TI  - [The current state of the brain-computer interface problem].
AB  - It was only 40 years ago that the first PC appeared. Over this period, rather
      short in historical terms, we have witnessed the revolutionary changes in lives
      of individuals and the entire society. Computer technologies are tightly
      connected with any field, either directly or indirectly. We can currently claim
      that computers are manifold superior to a human mind in terms of a number of
      parameters; however, machines lack the key feature: they are incapable of
      independent thinking (like a human). However, the key to successful development
      of humankind is collaboration between the brain and the computer rather than
      competition. Such collaboration when a computer broadens, supplements, or
      replaces some brain functions is known as the brain-computer interface. Our
      review focuses on real-life implementation of this collaboration.

PMID- 25945383
TI  - Retraction notice to: The AFB4 auxin receptor is a negative regulator of auxin
      signaling in seedlings.

PMID- 25945385
TI  - Legislators, CMS pull in reins on Medicare Advantage plans.

PMID- 25945384
TI  - Frontiers in noninvasive cardiac mapping rotors in atrial fibrillation-body
      surface frequency-phase mapping.
AB  - Experimental and clinical data demonstrate that atrial fibrillation (AF)
      maintenance in animals and groups of patients depends on localized reentrant
      sources localized primarily to the pulmonary veins and the left atrium posterior
      wall in paroxysmal AF but elsewhere, including the right atrium, in persistent
      AF. Moreover, AF can be eliminated by directly ablating AF-driving sources, or
      "rotors," that exhibit high- frequency periodic activity.

PMID- 25945386
TI  - Pharmacists experiment with pharmacogenomic management.

PMID- 25945387
TI  - Three benefit models improve specialty drug adherence.

PMID- 25945388
TI  - Pioneer ACOs: some unhitch wagons while others roll over rocky terrain.

PMID- 25945389
TI  - Alteration of Resting-State Brain Sensorimotor Connectivity following Spinal Cord
      Injury: A Resting-State Functional Magnetic Resonance Imaging Study.
AB  - Motor and sensory deficits after spinal cord injury (SCI) result in functional
      reorganization of the sensorimotor network. While several task-evoked functional
      magnetic resonance imaging (fMRI) studies demonstrated functional alteration of
      the sensorimotor network in SCI, there has been no study of the possible
      alteration of resting-state functional connectivity using resting-state fMRI. The
      aim of this study was to investigate the changes of brain functional connectivity
      in the sensorimotor cortex of patients with SCI. We evaluated the functional
      connectivity scores between brain areas within the sensorimotor network in 18
      patients with SCI and 18 controls. Our findings demonstrated that, compared with
      control subjects, patients with SCI showed increased functional connectivity
      between primary motor cortex and other motor areas, such as the supplementary
      motor area and basal ganglia. However, decreased functional connectivity between
      primary somatosensory cortex and secondary somatosensory cortex also was found in
      patients with SCI, compared with controls. These findings therefore demonstrated
      alteration of the resting-state sensorimotor network in patients with SCI, who
      showed increased connectivity between motor components, and decreased
      connectivity between sensory components, within the sensorimotor network,
      suggesting that motor components within the motor network increased in functional
      connectivity in order to compensate for motor deficits, whereas the sensory
      network did not show any such increases or compensation for sensory deficits. 

PMID- 25945391
TI  - An EPR spin probe study of liposomes from sunflower and soybean phospholipids.
AB  - Comparative properties of lecithin-based liposomes prepared from the mixed
      phospholipids of sunflower seeds, soybean and egg yolk were investigated by
      electron paramagnetic resonance (EPR) spectroscopy. For these investigations,
      stable nitroxide radicals, 1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl 5,7
      dimethyladamantane-1-carboxylate (DMAC-TEMPO), 5-doxylstearic acid (5-DSA) and 16
      doxylstearic acid (16-DSA) were used as spin probes. Binding of the spin probes
      to the liposome membranes resulted in a substantial increase of the apparent
      rotational diffusion correlation times. The EPR spectra of the incorporated
      nitroxides underwent temperature-dependent changes. For every spin probe, values
      of apparent enthalpy and entropy of activation were calculated from the
      temperature dependence of rotational diffusion correlation times via Arrhenius
      equation. In case of DMAC-TEMPO, the data point to differences between the
      phospholipid bilayer of liposomes derived from sunflower and soy lecithin, and
      some similarity between the sunflower and egg yolk liposomes. Anisotropic
      hyperfine interaction constants of DMAC-TEMPO and 16-DSA included in the
      liposomes have been analyzed and attributed to different micropolarity of the
      surroundings of the spin probes. The kinetics of EPR signal decay of DMAC-TEMPO
      in the presence of 2,2'-azobis(2-amidinopropane) suggest the better stability of
      the sunflower liposomes to lipid peroxidation as compared to the liposomes
      prepared from soy lecithin. 

PMID- 25945390
TI  - Mechanistic significance of the si-o-pd bond in the palladium-catalyzed cross
      coupling reactions of alkenylsilanolates.
AB  - Through the combination of reaction kinetics (both catalytic and stoichiometric)
      and solid-state characterization of arylpalladium(II) alkenylsilanolate
      complexes, the intermediacy of covalent adducts containing Si-O-Pd linkages in
      the cross-coupling reactions of organosilanolates has been unambiguously
      established. Two mechanistically distinct pathways have been demonstrated: (1)
      transmetalation via a neutral 8-Si-4 intermediate that dominates in the cross
      coupling of potassium alkenylsilanolates, and (2) transmetalation via an anionic
      10-Si-5 intermediate that dominates in the cross-coupling of cesium
      alkenylsilanolates. Arylpalladium(II) alkenylsilanolate complexes bearing various
      phosphine ligands (both bidentate and monodentate) have been isolated, fully
      characterized, and evaluated for their kinetic competence under thermal
      (stoichiometric) and anionic (catalytic) conditions. Comparison of the rates for
      thermal and anionic activation demonstrates that intermediates containing the Si
      O-Pd linkage are involved in the cross-coupling process. 

PMID- 25945392
TI  - Novel method of niosome generation using supercritical carbon dioxide part I:
      process mechanics.
AB  - A novel method for the production of non-ionic surfactant vesicles (niosomes)
      using an rapid expansion of supercritical solution (RESS)-based process coupled
      with a gas ejector is presented along with an investigation of parameters
      affecting niosome morphology, size and encapsulation efficiency of a 0.2 M D
      glucose solution in Tris buffer at physiological pH. The solubility of the non
      ionic surfactant polyoxyethylene(4) sorbitan monostearate in SC-CO2 was
      determined at three pressures (10, 15 and 20 MPa) and three temperatures (40, 50
      and 60  degrees C). Mole fraction of Tween61 in the vapor phase increased with
      pressure at 40  degrees C, but did not change with pressure at 50 or 60  degrees
      C. Solubility data were correlated using the Peng-Robinson equation of state
      (PREOS) with the Panagiotopoulos and Reid mixing rule. Vesicles were either
      multilamellar or unilamellar, depending on the degree of precipitation of the
      lipid formulation at the point of aqueous cargo introduction. Vesicle particle
      size distributions were bimodal, with the 80-99% of the liposomal volume
      contributed niosomes ranging in size from 3 to 7 MUm and the remaining niosomes
      ranging from 239 to 969 nm, depending on the system configuration. Encapsulation
      efficiency as high as 28% using the gas ejector to introduce the glucose cargo
      solution was achieved. Vesicle particle size and encapsulation efficiency were
      shown to be dependent on cargo droplet formation.

PMID- 25945393
TI  - Enhanced permeability across Caco-2 cell monolayers by specific mannosylating
      ligand of buserelin acetate proliposomes.
AB  - CONTEXT: Oral delivery of peptide and protein drugs still remains the area of
      challenges due to their low stability and permeability across GI tract. Among
      numerous attempts, the receptor-mediated drug targeting is a promising approach
      to enhance GI permeability. OBJECTIVE: The aim of this study was to prepare
      mannosylated buserelin acetate (MANS-BA) proliposome powders grafted with N
      octadecyl-d-mannopyranosylamine (SAMAN) as targeting moiety and evaluate their
      permeability across Caco-2 cell monolayers. MATERIALS AND METHODS: The MANS-BA
      proliposome powders were prepared by coprecipitation method. The targeting moiety
      SAMAN was synthesized in-house and confirmed by characterization using Fourier
      transform infrared (FTIR) and differential scanning calorimeter (DSC). RESULTS:
      The MANS-BA liposomes reconstituted from proliposome powders exhibited the
      oligolamellar vesicular structure of phospholipid bilayer. Their size, zeta
      potential and entrapment efficiency were in the ranges of 93.11-218.95 nm, -24.03
      to -37.15 mV and 21.12-33.80%, respectively. The permeability of reconstituted
      MANS-BA liposomes across Caco-2 cell monolayers was significantly enhanced to
      about 1.2- and 2.2-fold over those of conventional BA liposomes and solution,
      respectively. DISCUSSION: Increase in dicetylphosphate, cholesterol and SAMAN
      contents resulted in significant increase in size and zeta potential of
      reconstituted MAN-BA liposomes. The entrapment efficiency was increased with
      increasing dicetylphosphate and mannitol contents in liposomes containing
      cholesterol. CONCLUSIONS: The significantly enhanced permeability across Caco-2
      cell monolayers of MANS-BA liposomes might be due to the role of mannose receptor
      on intestinal enterocytes.

PMID- 25945394
TI  - Giant Negative Area Compressibility Tunable in a Soft Porous Framework Material.
AB  - A soft porous material [Zn(L)2(OH)2]n.Guest (where L is 4-(1H-naphtho[2,3
      d]imidazol-1-yl)benzoate, and Guest is water or methanol) exhibits the strongest
      ever observed negative area compressibility (NAC), an extremely rare property, as
      at hydrostatic pressure most materials shrink in all directions and few expand in
      one direction. This is the first NAC reported in metal-organic frameworks (MOFs),
      and its magnitude, clearly visible and by far the highest of all known materials,
      can be reversibly tuned by exchanging guests adsorbed from hydrostatic fluids.
      This counterintuitive strong NAC of [Zn(L)2(OH)2]n.Guest arises from the
      interplay of flexible [-Zn-O(H)-]n helices with layers of [-Zn-L-]4 quadrangular
      puckered rings comprising large channel voids. The compression of helices and
      flattening of puckered rings combine to give a giant piezo-mechanical response,
      applicable in ultrasensitive sensors and actuators. The extrinsic NAC response to
      different hydrostatic fluids is due to varied host-guest interactions affecting
      the mechanical strain within the range permitted by exceptionally high
      flexibility of the framework. 

PMID- 25945395
TI  - Magnetic elastomers for stretchable inductors.
AB  - In this work, silicone loaded with magnetic particles is investigated for
      creating a composite with higher permeability while still maintaining
      stretchability. Magnetic and mechanical properties are first characterized for
      composites based on both spherical and platelet particle geometries. The first
      magnetic-core stretchable inductors are then demonstrated using the resulting
      ferroelastomer. Solenoid inductors based on liquid metal galinstan are then
      demonstrated around a ferroelastomeric core and shown to survive uniaxial strains
      up to 100%. Soft elastomers loaded with magnetic particles were found to increase
      the core permeability and inductance density of stretchable inductors by nearly
      200%. 

PMID- 25945396
TI  - The number and ratio of positive lymph nodes affect pancreatic cancer patient
      survival after neoadjuvant therapy and pancreaticoduodenectomy.
AB  - AIMS: This study is to examine the significance of the number and ratio of
      positive nodes in post-neoadjuvant therapy pancreaticoduodenectomy (PD) for
      pancreatic ductal adenocarcinoma (PDAC). METHODS AND RESULTS: Our study
      population consisted of 398 consecutive PDAC patients, who completed neoadjuvant
      therapy and PD between 1999 and 2012. Lymph node status was classified as ypN0
      (node-negative), ypN1 (1-2 positive nodes) and ypN2 (>=3 positive nodes) and
      correlated with disease-free survival (DFS) and overall survival (OS). The ypN0,
      ypN1 and ypN2 was present in 183 (46.0%), 117 (29.4%) and 98 (24.6%) patients,
      respectively. Additionally, 162 (40.7%) had a lymph node ratio (LNR) <=0.19 and
      53 (13.3%) had a LNR >0.19. Patients with ypN1 disease had shorter DFS and OS
      than those with ypN0 disease, but better DFS and OS than those with ypN2 disease
      (P < 0.05). Similarly, patients with a LNR <= 0.19 had better DFS and OS than
      those with a LNR > 0.19 (P < 0.001). In multivariate analysis, both the number of
      positive nodes and LNR were independent prognostic factors for DFS and OS.
      CONCLUSIONS: Subclassification of post-therapy node-positive group into ypN1 (1-2
      positive nodes) and ypN2 (>=3 positive nodes) should be incorporated into the
      American Joint Committee on Cancer (AJCC) staging of PDAC patients.

PMID- 25945397
TI  - Mechanical Stress and the Induction of Lung Fibrosis via the Midkine Signaling
      Pathway.
AB  - RATIONALE: Lung-protective ventilatory strategies have been widely used in
      patients with acute respiratory distress syndrome (ARDS), but the ARDS mortality
      rate remains unacceptably high and there is no proven pharmacologic therapy.
      OBJECTIVES: Mechanical ventilation can induce oxidative stress and lung fibrosis,
      which may contribute to high dependency on ventilator support and increased ARDS
      mortality. We hypothesized that the novel cytokine, midkine (MK), which can be up
      regulated in oxidative stress, plays a key role in the pathogenesis of ARDS
      associated lung fibrosis. METHODS: Blood samples were collected from 17 patients
      with ARDS and 10 healthy donors. Human lung epithelial cells were challenged with
      hydrogen chloride followed by mechanical stretch for 72 hours. Wild-type and MK
      gene-deficient (MK(-/-)) mice received two-hit injury of acid aspiration and
      mechanical ventilation, and were monitored for 14 days. MEASUREMENTS AND MAIN
      RESULTS: Plasma concentrations of MK were higher in patients with ARDS than in
      healthy volunteers. Exposure to mechanical stretch of lung epithelial cells led
      to an epithelial-mesenchymal transition profile associated with increased
      expression of angiotensin-converting enzyme, which was attenuated by silencing
      MK, its receptor Notch2, or NADP reduced oxidase 1. An increase in collagen
      deposition and hydroxyproline level and a decrease in lung tissue compliance seen
      in wild-type mice were largely attenuated in MK(-/-) mice. CONCLUSIONS:
      Mechanical stretch can induce an epithelial-mesenchymal transition phenotype
      mediated by the MK-Notch2-angiotensin-converting enzyme signaling pathway,
      contributing to lung remodeling. The MK pathway is a potential therapeutic target
      in the context of ARDS-associated lung fibrosis.

PMID- 25945398
TI  - A Novel Cylindrical Representation for Characterizing Intrinsic Properties of
      Protein Sequences.
AB  - The composition and sequence order of amino acid residues are the two most
      important characteristics to describe a protein sequence. Graphical
      representations facilitate visualization of biological sequences and produce
      biologically useful numerical descriptors. In this paper, we propose a novel
      cylindrical representation by placing the 20 amino acid residue types in a circle
      and sequence positions along the z axis. This representation allows visualization
      of the composition and sequence order of amino acids at the same time. Ten
      numerical descriptors and one weighted numerical descriptor have been developed
      to quantitatively describe intrinsic properties of protein sequences on the basis
      of the cylindrical model. Their applications to similarity/dissimilarity analysis
      of nine ND5 proteins indicated that these numerical descriptors are more
      effective than several classical numerical matrices. Thus, the cylindrical
      representation obtained here provides a new useful tool for visualizing and
      charactering protein sequences. An online server is available at
      http://biophy.dzu.edu.cn:8080/CNumD/input.jsp . 

PMID- 25945399
TI  - Role of Flagella in Adhesion of Escherichia coli to Abiotic Surfaces.
AB  - Understanding the interfacial activity of bacteria is of critical importance due
      to the huge economic and public health implications associated with surface
      fouling and biofilm formation. The complexity of the process and difficulties of
      predicting microbial adhesion to novel materials demand study of the properties
      of specific bacterial surface features and their potential contribution to
      surface attachment. Here, we examine flagella, cell appendages primarily studied
      for their cell motility function, to elucidate their potential role in the
      surface adhesion of Escherichia coli-a model organism and potential pathogen. We
      use self-assembled monolayers (SAMs) of thiol-bearing molecules on gold films to
      generate surfaces of varying hydrophobicity, and measure adhesion of purified
      flagella using quartz crystal microbalance. We show that flagella adhere more
      extensively and bind more tightly to hydrophobic SAMs than to hydrophilic ones,
      and we propose a two-step vs a single-step adhesion mechanism that accounts for
      the observed dissipation and frequency changes for the two types of surfaces,
      respectively. Subsequently, study of the adhesion of wild-type and flagella
      knockout cells confirms that flagella improve adhesion to hydrophobic substrates,
      whereas cells lacking flagella do not show preferred affinity to hydrophobic
      substrates. Together, these properties bring about an interesting ability of
      cells with flagella to stabilize emulsions of aqueous culture and dodecane, not
      observed for cells lacking flagella. This work contributes to our overall
      understanding of nonspecific bacterial adhesion and confirms that flagella,
      beyond motility, may play an important role in surface adhesion. 

PMID- 25945400
TI  - Capillary pressure-saturation relations for supercritical CO2 and brine in
      limestone/dolomite sands: implications for geologic carbon sequestration in
      carbonate reservoirs.
AB  - In geologic carbon sequestration, capillary pressure (Pc)-saturation (Sw)
      relations are needed to predict reservoir processes. Capillarity and its
      hysteresis have been extensively studied in oil-water and gas-water systems, but
      few measurements have been reported for supercritical (sc) CO2-water. Here, Pc-Sw
      relations of scCO2 displacing brine (drainage), and brine rewetting (imbibition)
      were studied to understand CO2 transport and trapping behavior under reservoir
      conditions. Hysteretic drainage and imbibition Pc-Sw curves were measured in
      limestone sands at 45  degrees C under elevated pressures (8.5 and 12.0 MPa) for
      scCO2-brine, and in limestone and dolomite sands at 23  degrees C (0.1 MPa) for
      air-brine using a new computer programmed porous plate apparatus. scCO2-brine
      drainage and imbibition curves shifted to lower Pc relative to predictions based
      on interfacial tension, and therefore deviated from capillary scaling predictions
      for hydrophilic interactions. Fitting universal scaled drainage and imbibition
      curves show that wettability alteration resulted from scCO2 exposure over the
      course of months-long experiments. Residual trapping of the nonwetting phases was
      determined at Pc = 0 during imbibition. Amounts of trapped scCO2 were
      significantly larger than for those for air, and increased with pressure (depth),
      initial scCO2 saturation, and time. These results have important implications for
      scCO2 distribution, trapping, and leakage potential.

PMID- 25945402
TI  - Agrobacterium tumefaciens and Interkingdom Genetic Exchange.

PMID- 25945401
TI  - Cobalt(III)-Catalyzed C-H Bond Amidation with Isocyanates.
AB  - The first examples of cobalt(III)-catalyzed C-H bond addition to isocyanates are
      described, providing a convergent strategy for arene and heteroarene amidation.
      Using a robust air- and moisture-stable catalyst, this transformation
      demonstrates a broad isocyanate scope and good functional-group compatibility and
      has been performed on gram scale. 

PMID- 25945403
TI  - Synthetic ciguatoxin CTX 3C induces a rapid imbalance in neuronal excitability.
AB  - Ciguatera is a human global disease caused by the consumption of contaminated
      fish that have accumulated ciguatoxins (CTXs), sodium channel activator toxins.
      Symptoms of ciguatera include neurological alterations such as paraesthesiae,
      dysaesthesiae, depression, and heightened nociperception, among others. An
      important issue to understand these long-term neurological alterations is to
      establish the role that changes in activity produced by CTX 3C represent to
      neurons. Here, the effects of synthetic ciguatoxin CTX 3C on membrane potential,
      spontaneous spiking, and properties of synaptic transmission in cultured cortical
      neurons of 11-18 days in vitro (DIV) were evaluated using electrophysiological
      approaches. CTX 3C induced a large depolarization that decreased neuronal firing
      and caused a rapid inward tonic current that was primarily GABAergic. Moreover,
      the toxin enhanced the amplitude of miniature postsynaptic inhibitory currents
      (mIPSCs), whereas it decreased the amplitude of miniature postsynaptic excitatory
      currents (mEPSCs). The frequency of mIPSCs increased, whereas the frequency of
      mEPSCs remained unaltered. We describe, for the first time, that a rapid membrane
      depolarization caused by CTX 3C in cortical neurons activates mechanisms that
      tend to suppress electrical activity by shifting the balance between excitatory
      and inhibitory synaptic transmission toward inhibition. Indeed, these results
      suggest that the acute effects of CTX on synaptic transmission could underlie
      some of the neurological symptoms caused by ciguatera in humans.

PMID- 25945404
TI  - US stem cell clinics, patient safety, and the FDA.
AB  - Scholarship on patients accessing unproven stem cell interventions is dominated
      by research addressing 'stem cell tourism' to such countries as China, India,
      Mexico, and the Ukraine. However, clinics marketing 'adipose-derived mesenchymal
      stem cell treatments' are proliferating across the USA. These businesses
      typically claim to operate in compliance with federal regulations, but careful
      review of their commercial practices suggests that such clinics are marketing
      unapproved and noncompliant biological drugs. 

PMID- 25945405
TI  - IgM exacerbates glomerular disease progression in complement-induced
      glomerulopathy.
AB  - Although glomerular immunoglobulin M (IgM) deposition occurs in a variety of
      glomerular diseases, the mechanism of deposition and its clinical significance
      remain controversial. Some have theorized IgM becomes passively trapped in areas
      of glomerulosclerosis. However, recent studies found that IgM specifically binds
      damaged glomeruli. Therefore, we tested whether natural IgM binds to neo-epitopes
      exposed after insults to the glomerulus and exacerbates disease in mice deficient
      in the complement regulatory protein factor H; a model of non-sclerotic and
      nonimmune-complex glomerular disease. Immunofluorescence microscopy demonstrated
      mesangial and capillary loop deposition of IgM, whereas ultrastructural analysis
      found IgM deposition on endothelial cells and subendothelial areas. Factor H
      deficient mice lacking B cells were protected from renal damage, as evidenced by
      milder histologic lesions on light and electron microscopy. IgM, but not IgG,
      from wild-type mice bound to cultured murine mesangial cells. Furthermore,
      injection of purified IgM into mice lacking B cells bound within the glomeruli
      and induced proteinuria. A monoclonal natural IgM-recognizing phospholipids also
      bound to glomeruli in vivo and induced albuminuria. Thus, our results indicate
      specific IgM antibodies bind to glomerular epitopes and that IgM contributes to
      the progression of glomerular damage in this mouse model of non-sclerotic
      glomerular disease. 

PMID- 25945407
TI  - Optimal convection volume for improving patient outcomes in an international
      incident dialysis cohort treated with online hemodiafiltration.
AB  - Online hemodiafiltration (OL-HDF), the most efficient renal replacement therapy,
      enables enhanced removal of small and large uremic toxins by combining diffusive
      and convective solute transport. Randomized controlled trials on prevalent
      chronic kidney disease (CKD) patients showed improved patient survival with high
      volume OL-HDF, underlining the effect of convection volume (CV). This
      retrospective international study was conducted in a large cohort of incident CKD
      patients to determine the CV threshold and range associated with survival
      advantage. Data were extracted from a cohort of adult CKD patients treated by
      post-dilution OL-HDF over a 101-month period. In total, 2293 patients with a
      minimum of 2 years of follow-up were analyzed using advanced statistical tools,
      including cubic spline analyses for determination of the CV range over which a
      survival increase was observed. The relative survival rate of OL-HDF patients,
      adjusted for age, gender, comorbidities, vascular access, albumin, C-reactive
      protein, and dialysis dose, was found to increase at about 55 l/week of CV and to
      stay increased up to about 75 l/week. Similar analysis of pre-dialysis beta2
      microglobin (marker of middle-molecule uremic toxins) concentrations found a
      nearly linear decrease in marker concentration as CV increased from 40 to 75
      l/week. Analysis of log C-reactive protein levels showed a decrease over the same
      CV range. Thus, a convection dose target based on convection volume should be
      considered and needs to be confirmed by prospective trials as a new determinant
      of dialysis adequacy. 

PMID- 25945406
TI  - Comparative risk of renal, cardiovascular, and mortality outcomes in controlled,
      uncontrolled resistant, and nonresistant hypertension.
AB  - We sought to compare the risk of end-stage renal disease (ESRD), ischemic heart
      event (IHE), congestive heart failure (CHF), cerebrovascular accident (CVA), and
      all-cause mortality among 470,386 individuals with resistant and nonresistant
      hypertension (non-RH). Resistant hypertension (60,327 individuals) was
      subcategorized into two groups: 23,104 patients with cRH (controlled on four or
      more medicines) and 37,223 patients with uRH (uncontrolled on three or more
      medicines) in a 5-year retrospective cohort study. Cox proportional hazard
      modeling was used to estimate hazard ratios adjusting for age, gender, race, body
      mass index, chronic kidney disease (CKD), and comorbidities. Resistant
      hypertension (cRH and uRH), compared with non-RH, had multivariable adjusted
      hazard ratios (95% confidence intervals) of 1.32 (1.27-1.37), 1.24 (1.20-1.28),
      1.46 (1.40-1.52), 1.14 (1.10-1.19), and 1.06 (1.03-1.08) for ESRD, IHE, CHF, CVA,
      and mortality, respectively. Comparison of uRH with cRH had hazard ratios of 1.25
      (1.18-1.33), 1.04 (0.99-1.10), 0.94 (0.89-1.01), 1.23 (1.14-1.31), and 1.01 (0.97
      1.05) for ESRD, IHE, CHF, CVA, and mortality, respectively. Men and Hispanics had
      a greater risk for ESRD within all three cohorts. Individuals with resistant
      hypertension had a greater risk for ESRD, IHE, CHF, CVA, and mortality. The risk
      of ESRD and CVA were 25% and 23% greater, respectively, in uRH compared with cRH,
      supporting the linkage between blood pressure and both outcomes. 

PMID- 25945409
TI  - Atomic-Oxygen-Durable and Electrically-Conductive CNT-POSS-Polyimide Flexible
      Films for Space Applications.
AB  - In low Earth orbit (LEO), hazards such as atomic oxygen (AO) or electrostatic
      discharge (ESD) degrade polymeric materials, specifically, the extensively used
      polyimide (PI) Kapton. We prepared PI-based nanocomposite films that show both AO
      durability and ESD protection by incorporating polyhedral oligomeric
      silsesquioxane (POSS) and carbon nanotube (CNT) additives. The unique methods
      that are reported prevent CNT agglomeration and degradation of the CNT properties
      that are common in dispersion-based processes. The influence of the POSS content
      on the electrical, mechanical, and thermo-optical properties of the CNT-POSS-PI
      films was investigated and compared to those of control PI and CNT-PI films. CNT
      POSS-PI films with 5 and 15 wt % POSS content exhibited sheet resistivities as
      low as 200 Omega/?, and these resistivities remained essentially unchanged after
      exposure to AO with a fluence of ~2.3 * 10(20) O atoms cm(-2). CNT-POSS-PI films
      with 15 wt % POSS content exhibited an erosion yield of 4.8 * 10(-25) cm(3) O
      atom(-1) under 2.3 * 10(20) O atoms cm(-2) AO fluence, roughly one order of
      magnitude lower than that of pure PI films. The durability of the conductivity of
      the composite films was demonstrated by rolling film samples with a tight radius
      up to 300 times. The stability of the films to thermal cycling and ionizing
      radiation was also demonstrated. These properties make the prepared CNT-POSS-PI
      films with 15 wt % POSS content excellent candidates for applications where AO
      durability and electrical conductivity are required for flexible and thermally
      stable materials. Hence, they are suggested here for LEO applications such as the
      outer layers of spacecraft thermal blankets. 

PMID- 25945408
TI  - Smad3 deficiency protects mice from obesity-induced podocyte injury that precedes
      insulin resistance.
AB  - Signaling by TGF-beta/Smad3 plays a key role in renal fibrosis. As obesity is one
      of the major risk factors of chronic and end-stage renal disease, we studied the
      role of Smad3 signaling in the pathogenesis of obesity-related renal disease.
      After switching to a high fat diet, the onset of Smad3 C-terminal
      phosphorylation, increase in albuminuria, and the early stages of peripheral and
      renal insulin resistance occurred at 1 day, and 4 and 8 weeks, respectively, in
      C57BL/6 mice. The loss of synaptopodin, a functional marker of podocytes, and
      phosphorylation of the Smad3 linker region (T179 and S213) appeared after 4 weeks
      of the high fat diet. This suggests a temporal pattern of Smad3 signaling
      activation leading to kidney injury and subsequent insulin resistance in the
      development of obesity-related renal disease. In vivo, Smad3 knockout attenuated
      the high fat diet-induced proteinuria, renal fibrosis, overall podocyte injury,
      and mitochondrial dysfunction in podocytes. In vitro palmitate caused a rapid
      activation of Smad3 in 30 min, loss of synaptopodin in 2 days, and impaired
      insulin signaling in 3 days in isolated mouse podocytes. Blockade of either Smad3
      phosphorylation by SIS3 (a Smad3 inhibitor) or T179 phosphorylation by
      flavopiridol (a CDK9 inhibitor) prevented the palmitate-induced loss of
      synaptopodin and mitochondrial function in podocytes. Thus, Smad3 signaling plays
      essential roles in obesity-related renal disease and may be a novel therapeutic
      target. 

PMID- 25945410
TI  - Comparative efficacy and safety of selective serotonin reuptake inhibitors and
      serotonin-norepinephrine reuptake inhibitors in older adults: a network meta
      analysis.
AB  - OBJECTIVES: To establish the comparative efficacy and safety of selective
      serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors in
      older adults using the network meta-analysis approach. DESIGN: Systematic review
      and network meta-analysis. PARTICIPANTS: Individuals aged 60 and older.
      MEASUREMENTS: Data on partial response (defined as at least 50% reduction in
      depression score from baseline) and safety (dizziness, vertigo, syncope, falls,
      loss of consciousness) were extracted. A Bayesian network meta-analysis was
      performed on the efficacy and safety outcomes, and relative risks (RRs) with 95%
      credible intervals (CrIs) were produced. RESULTS: Fifteen randomized controlled
      trials were eligible for inclusion in the analysis. Citalopram, escitalopram,
      paroxetine, duloxetine, venlafaxine, fluoxetine, and sertraline were represented.
      Reporting on partial response and dizziness was sufficient to conduct a network
      meta-analysis. Reporting on other outcomes was sparse. For partial response,
      sertraline (RR=1.28), paroxetine (RR=1.48), and duloxetine (RR=1.62) were
      significantly better than placebo. The remaining interventions yielded RRs lower
      than 1.20. For dizziness, duloxetine (RR=3.18) and venlafaxine (RR=2.94) were
      statistically significantly worse than placebo. Compared with placebo, sertraline
      had the lowest RR for dizziness (1.14) and fluoxetine the second lowest (1.31).
      Citalopram, escitalopram, and paroxetine all had RRs between 1.4 and 1.7.
      CONCLUSION: There was clear evidence of the effectiveness of sertraline,
      paroxetine, and duloxetine. There also appears to be a hierarchy of safety
      associated with the different antidepressants, although there appears to be a
      dearth of reporting of safety outcomes.

PMID- 25945411
TI  - Correlation of central memory CD4+ T-Cell decrease in the peripheral blood with
      disease progression in SIVmac251-infected Chinese rhesus macaques.
AB  - BACKGROUND: Correlation of CD4(+) Tcm cells in the peripheral blood to disease
      progression in SIVmac251 infection was examined in Chinese rhesus macaques.
      METHODS: Plasma viral RNA loads were measured by a quantitative real-time reverse
      transcription-PCR (qRT-PCR) assay for SIV gag. Disease progression was determined
      based on time of survival. Phenotyping of CD4(+) T-cell subsets in the peripheral
      blood was longitudinally performed by flow cytometry. RESULTS: Although CD4(+) T
      cell decrease and low CD4(+)/CD8(+) T-cell ratio in the peripheral blood after
      SIVmac251 infection did not correlate with disease progression, CD4(+) Tcm cell
      decrease was observed to be correlated to disease progression in the SIVmac251
      infected Chinese rhesus macaques. CONCLUSIONS: Our findings suggest that CD4(+)
      Tcm cell decrease could be used as a predictive marker for defining the
      pathogenesis of the SIV disease and consequently HIV/SIV vaccine efficacy in
      Chinese rhesus macaques.

PMID- 25945412
TI  - Toxicity of polyunsaturated aldehydes of diatoms to Indo-Pacific bioindicator
      organism Echinometra mathaei.
AB  - Although it is well known suitability of early developmental stages of sea urchin
      as recommended model for pollutant toxicity testing, little is known about the
      sensitivity of Indo-Pacific species Echinometra mathaei to polyunsaturated
      aldehydes. In this study, the effect of three short chain aldehydes, 2,4
      decadienal (DD), 2,4-octadienal (OD) and 2,4-heptadienal (HD), normally found in
      many diatoms, such as Skeletonema costatum, Skeletonema marinoi and Thalassiosira
      rotula, was evaluated on larval development of E. mathaei embryos. Aldehydes
      affected larval development in a dose-dependent manner, in particular HD>OD>DD;
      the results of this study highlighted the higher sensitivity of this species
      toward aldehydes compared with data registered for other sea urchin species. In
      comparison with studies reported in the literature, contrasting results were
      observed during our tests; therefore, an increasing toxic effect was registered
      with decreasing the chain length of aldehydes. This work could provide new
      insights in the development of new toxicological assays toward most sensitive
      species. 

PMID- 25945413
TI  - Amphibian (Euphlyctis cyanophlyctis) in vitro ovarian culture system to assess
      impact of aquatic agrochemical contaminants on female reproduction.
AB  - The present study is an attempt to screen impacts of aquatic agrochemical
      contaminants (acephate, atrazine and cypermethrin) on development and growth of
      follicles, in in vitro-cultured ovarian fragments of frog (Euphlyctis
      cyanophlyctis). Ovarian lobes removed surgically from gravid females were cut
      into small pieces and cultured in vitro in presence of graded (0.01 or 0.1 MUg/ml
      of culture medium) concentrations of test chemicals or estradiol-17beta (positive
      controls) or culture medium alone (controls) in quadruplicate sets at 23 +/- 1 
      degrees C temperature for 20 days in a humidified sterile chamber. On 21st day,
      they were fixed in Bouin's fluid and used for differential follicle counting (n =
      3 sets) and histology (n = 1 set). In vitro exposure of ovarian fragments to test
      chemicals caused a decline in previtellogenic follicles, maintenance of large
      yolky follicles, incorporation of brown granules into early vitellogenic
      follicles and decrease in follicular atresia compared to corresponding controls.
      These results suggest that ovarian follicles are greatly sensitive to chemical
      exposure during their transition from previtellogenic to vitellogenic growth
      phase and in vitro ovarian culture system may be used as a tool to assess the
      effects of aquatic agrochemical contaminants on ovarian function.

PMID- 25945414
TI  - Oncogenic MAGEA-TRIM28 ubiquitin ligase downregulates autophagy by ubiquitinating
      and degrading AMPK in cancer.
AB  - Autophagy is commonly altered in cancer and has a complicated, but important role
      in regulation of tumor growth. Autophagy is often tumor suppressive in the early
      stages of cancer development, but contributes to the late stages of tumor growth.
      Because of this, putative oncogenes that modulate autophagy signaling are
      especially interesting. Here we discuss our recent work detailing the function of
      the MAGEA-TRIM28 ubiquitin ligase as an oncogene product that targets
      PRKAA1/AMPKalpha1 for ubiquitination and proteasome-mediated degradation.
      Degradation of AMPK, a master cellular energy sensor and regulator, by MAGEA
      TRIM28 results in significantly reduced autophagy and changes in cellular
      metabolism, including upregulation of MTOR signaling. Overall, expression of
      MAGEA3 (or MAGEA6) and degradation of AMPK is sufficient to induce transformation
      of normal cells and promote multiple hallmarks of cancer. 

PMID- 25945416
TI  - Gone in seconds: praxis, performance, and peculiarities of ultrafast chiral
      liquid chromatography with superficially porous particles.
AB  - A variety of brush-type chiral stationary phases (CSPs) were developed using
      superficially porous particles (SPPs). Given their high efficiencies and
      relatively low back pressures, columns containing these particles were
      particularly advantageous for ultrafast "chiral" separations in the 4-40 s range.
      Further, they were used in all mobile phase modes and with high flow rates and
      pressures to separate over 60 pairs of enantiomers. When operating under these
      conditions, both instrumentation and column packing must be modified or optimized
      so as not to limit separation performance and quality. Further, frictional
      heating results in axial thermal gradients of up to 16  degrees C and radial
      temperature gradients up to 8  degrees C, which can produce interesting secondary
      effects in enantiomeric separations. It is shown that the kinetic behavior of
      various CSPs can differ from one another as much as they differ from the well
      studied C18 reversed phase media. Three additional interesting aspects of this
      work are (a) the first kinetic evidence of two different chiral recognition
      mechanisms, (b) a demonstration of increased efficiencies at higher flow rates
      for specific separations, and 

PMID- 25945415
TI  - Apoptotic effects of high-dose rapamycin occur in S-phase of the cell cycle.
AB  - Mutations in genes encoding regulators of mTOR, the mammalian target of
      rapamycin, commonly provide survival signals in cancer cells. Rapamycin and
      analogs of rapamycin have been used with limited success in clinical trials to
      target mTOR-dependent survival signals in a variety of human cancers. Suppression
      of mTOR predominantly causes G1 cell cycle arrest, which likely contributes to
      the ineffectiveness of rapamycin-based therapeutic strategies. While rapamycin
      causes the accumulation of cells in G1, its effect in other cell cycle phases
      remains largely unexplored. We report here that when synchronized MDA-MB-231
      breast cancer cells are allowed to progress into S-phase from G1, rapamycin
      activates the apoptotic machinery with a concomitant increase in cell death. In
      Calu-1 lung cancer cells, rapamycin induced a feedback increase in Akt
      phosphorylation at Ser473 in S-phase that mitigated rapamycin-induced apoptosis.
      However, sensitivity to rapamycin in S-phase could be reestablished if Akt
      phosphorylation was suppressed. We recently reported that glutamine (Gln)
      deprivation causes K-Ras mutant cancer cells to aberrantly arrest primarily in S
      phase. Consistent with observed sensitivity of S-phase cells to rapamycin,
      interfering with Gln utilization sensitized both MDA-MB-231 and Calu-1 K-Ras
      mutant cancer cells to the apoptotic effect of rapamycin. Importantly, rapamycin
      induced substantially higher levels of cell death upon Gln depletion than that
      observed in cancer cells that were allowed to progress through S-phase after
      being synchronized in G1. We postulate that exploiting metabolic vulnerabilities
      in cancer cells such as S-phase arrest observed with K-Ras-driven cancer cells
      deprived of Gln, could be of great therapeutic potential. 

PMID- 25945417
TI  - Stability Study of Isoniazid in Human Plasma: Practical Aspects for Laboratories.

PMID- 25945418
TI  - Family Profiles of Expressed Emotion in Adolescent Patients With Anorexia Nervosa
      and Their Parents.
AB  - The current study examined expressed emotion (EE) among families of adolescents
      with anorexia nervosa (AN) participating in a treatment study. EE ratings were
      made from 110 adolescents toward their parents and from parents toward their
      children using videotaped family interviews. Participants were 92% female and 75%
      Caucasian with a mean age of 14.41 years. Four family profiles were created (low
      patient EE/low parent EE, high patient EE/high parent EE, low patient EE/high
      parent EE, high patient EE/low parent EE). Family EE profile was not related to
      full remission at end of treatment. Groups were then combined according to EE
      level of parent. The low parent group (defined as low on criticism, hostility,
      and emotional overinvolvement) had significantly lower scores on a measure of
      eating disorder psychopathology than the high parent group at the end of
      treatment. Patients with AN in low EE families do better in treatment than those
      patients belonging to high EE families. These findings are true regardless of the
      EE status of the patient.

PMID- 25945419
TI  - MiR-15a and miR-16 induce autophagy and enhance chemosensitivity of Camptothecin.
AB  - It has been reported that persistent or excessive autophagy promotes cancer cell
      death during chemotherapy, either by enhancing the induction of apoptosis or
      mediating autophagic cell death. Here, we show that miR-15a and miR-16 are potent
      inducers of autophagy. Rictor, a component of mTORC2 complex, is directly
      targeted by miR-15a/16. Overexpression of miR-15a/16 or depletion of endogenous
      Rictor attenuates the phosphorylation of mTORC1 and p70S6K, inhibits cell
      proliferation and G1/S cell cycle transition in human cervical carcinoma HeLa
      cells. Moreover, miR-15a/16 dramatically enhances anticancer drug camptothecin
      (CPT)-induced autophagy and apoptotic cell death in HeLa cells. Collectively,
      these data demonstrate that miR-15a/16 induced autophagy contribute partly to
      their inhibition of cell proliferation and enhanced chemotherapeutic efficacy of
      CPT. 

PMID- 25945420
TI  - The feasibility and acceptability of reducing salt in partially baked bread: a
      Spanish case study.
AB  - OBJECTIVE: Bread is a staple of the Mediterranean diet but contributes
      substantially to its salt content (19 % in Spain). The objective of the present
      study was to assess the feasibility and acceptability of salt reduction in
      partially baked breads, partly replacing salt (NaCl) with a potassium salt, with
      subsequent follow-up. DESIGN: During 2013, nine breads already on the market (1.8
      % NaCl flour basis) had 0.5 % of NaCl replaced with potassium citrate (27.7 %
      reduction in sodium) and were commercialized in Spain. Later, breads were baked
      in bake-off stores and sold ready-to-eat to consumers. This market test was
      evaluated by comparing the sales between standard- v. reduced-salt breads and the
      complaints related to flavour attributes. The wholesalers involved in the market
      test were then surveyed. SETTING: Spain. RESULTS: The market test confirmed good
      acceptance of the reduced-salt breads, as 2013 sales were 3678 tonnes v. 2012
      sales of 3577 tonnes for the same standard breads. No complaints were received.
      The wholesaler survey showed, in general, little awareness of salt reduction.
      CONCLUSIONS: It is feasible that potassium citrate can reduce the salt content of
      bread without negatively affecting sales or complaints. This shows potential for
      introducing this type of bread on a larger scale.

PMID- 25945421
TI  - Publish early--an invitation for graduate students.

PMID- 25945422
TI  - CYP2E1 Rsa Iota/Pst Iota polymorphism and lung cancer susceptibility: a meta
      analysis involving 10,947 subjects.
AB  - Many studies have examined the association between the CYP2E1 Rsa Iota/Pst Iota
      (rs3813867) polymorphism gene polymorphisms and lung cancer risk in various
      populations, but their results have been inconsistent. The PubMed and CNKI
      database was searched for case-control studies published up to October 2013. Data
      were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI)
      were calculated. In this meta-analysis, we assessed 23 published studies
      involving comprising 4727 lung cancer cases and 6220 controls of the association
      between CYP2E1 Rsa Iota/Pst Iota polymorphism and lung cancer risk. For the
      homozygote c2/c2 and c2 allele carriers (c1/c2 + c2/c2), the pooled ORs for all
      studies were 0.73(95% CI = 0.62-0.84; P = 0.005 for heterogeneity) and 0.84 (95%
      CI = 0.77-0.92; P = 0.001 for heterogeneity) when compared with the homozygous
      wild-type genotype (c1/c1). In the stratified analysis by ethnicity, the same
      significantly risks were found among Asians and mixed population for both the c2
      allele carriers and homozygote c2/c2. However, no significant associations were
      found in Caucasian population all genetic models. This updated meta-analysis
      suggests that CYP2E1 Rsa Iota/Pst Iota c2 allele is a decreased risk factor for
      the developing lung cancer among Asians and mixed population. 

PMID- 25945423
TI  - Ecotoxicology of polychlorinated biphenyls in fish--a critical review.
AB  - Polychlorinated biphenyls (PCBs) are widespread persistent anthropogenic
      contaminants that can accumulate in tissues of fish. The toxicity of PCBs and
      their transformation products has been investigated for nearly 50 years, but
      there is a lack of consensus regarding the effects of these environmental
      contaminants on wild fish populations. The objective of this review is to
      critically examine these investigations and evaluate publicly available databases
      for evidence of effects of PCBs in wild fish. Biological activity of PCBs is
      limited to a small proportion of PCB congeners [e.g., dioxin-like PCBs (DL-PCBs)]
      and occurs at concentrations that are typically orders of magnitude higher than
      PCB levels detected in wild fish. Induction of biomarkers consistent with PCB
      exposure (e.g., induction of cytochrome P450 monooxygenase system) has been
      evaluated frequently and shown to be induced in fish from some environments, but
      there does not appear to be consistent reports of damage (i.e., biomarkers of
      effect) to biomolecules (i.e., oxidative injury) in these fish. Numerous
      investigations of endocrine system dysfunction or effects on other organ systems
      have been conducted in wild fish, but collectively there is no consistent
      evidence of PCB effects on these systems in wild fish. Early life stage toxicity
      of DL-PCBs does not appear to occur at concentrations reported in wild fish
      embryos, and results do not support an association between PCBs and decreased
      survival of early life stages of wild fish. Overall, there appears to be little
      evidence that PCBs have had any widespread effect on the health or survival of
      wild fish. 

PMID- 25945424
TI  - Letter: a case supporting the use of rescue infliximab therapy for fulminant
      ulcerative colitis in pregnancy--authors' reply.

PMID- 25945425
TI  - Qualitative synthesis and systematic review of otolaryngology in undergraduate
      medical education.
AB  - OBJECTIVE: Although 25% of primary care complaints are otolaryngology related,
      otolaryngology instruction is not required in most medical schools. Our aim was
      to systematically review existing literature on the inclusion of otolaryngology
      in undergraduate medical education. DATA SOURCES: PubMed, Embase, Cumulative
      Index to Nursing and Allied Health Literature, and Education Resources
      Information Center. STUDY DESIGN/REVIEW METHODS: Our search encompassed all
      indexed years through December 29, 2014. Inclusion criteria were English
      language, original human data, and a focus on medical student education. Data
      regarding study design, teacher, educational topic, educational methods, and
      setting were extracted from each article. Two investigators independently
      reviewed all articles. RESULTS: Our initial search yielded 436 articles; 87
      underwent full-text evaluation and 47 remained in the final review. The majority
      of studies were conducted in the United States (40%), United Kingdom (23%), and
      Canada (17%) and represented a single institutional experience. Studies were
      classified as needs assessments (36%), curriculum descriptions (15%), educational
      methods (36%), and skills assessments (32%); 81% were levels of evidence 3 or 4.
      Most reports indicated that otolaryngology rotations are not compulsory.
      CONCLUSIONS: Studies indicated the need for increased exposure to otolaryngology.
      Educational methods such as team-based learning, simulation, online learning, and
      clinical skills assessments may offer ways to increase exposure without
      overburdening clinical faculty and require further study. Data suggest that a
      universal otolaryngology medical student curriculum would be valuable and aid in
      resource sharing across institutions. We recommend that an assessment be
      performed to determine topics and skills that should comprise this curriculum.
      LEVEL OF EVIDENCE: NA.

PMID- 25945426
TI  - A More Robust Test of the Penrose Hypothesis.

PMID- 25945427
TI  - Transcatheter Fontan takedown.
AB  - Early failure of the Fontan circulation is rare in the current era but remains
      associated with a high mortality rate. Surgical Fontan takedown has evolved as
      one of the strategies to stabilize the circulation, improve survival, and allow
      for a future attempt at Fontan completion. We have completed Transcatheter fontan
      takedown in three patients with extracardiac conduits 0.8-6 months following
      their Fontan operations. Superior vena cava flow was redirected into only the
      pulmonary arteries by occluding the conduit with a vascular plug between the
      pulmonary arteries and fenestration and unrestrictive inferior vena cava flow was
      redirected into only the atrium by stenting and enlarging the fenestration. There
      were no procedure related complications. All patients had resolution of large
      volume chylous pleural effusions. One patient had resolution of protein-losing
      enteropathy, two patients had improvement of plastic bronchitis. Two of three
      patients remain alive at latest follow-up (4-24 months). This early experience
      suggests that Transcatheter fontan takedown is technically feasible and may be an
      alternative to surgical takedown in select patients with early failure of the
      Fontan circulation.

PMID- 25945428
TI  - Promoting sympathovagal balance in multiple sclerosis; pharmacological, non
      pharmacological, and surgical strategies.
AB  - Accumulated evidence suggests that cardiovascular autonomic nervous system (ANS)
      dysfunction may be the underlying cause of many MS clinical presentations,
      including neurodegeneration and reduced response to immunomodulatory therapies,
      depression, fatigue and sleep disorders, migraine, osteoporosis, and chronic
      cerebrospinal venous insufficiency, the newer MS vascular etiology. We have
      recently described the genetic, epigenetic, and environmental factors with the
      potential influencing ANS activity, and the interactions among these factors.
      This review expands upon previous ones, describing the pharmacological, non
      pharmacological, and surgical strategies that could be adopted to prevent and
      minimize the deterioration in ANS function, promoting a state of sympathovagal
      balance. However, these strategies should not be applied as "one size fits all",
      but should take into account the nature and the degree of ANS dysfunction. These
      strategies would be effective in improving ANS function not only in MS, but also
      in other autoimmune and neurodegenerative diseases, where the dysfunction of this
      system plays a role. 

PMID- 25945429
TI  - Season's appreciations.
AB  - To follow the tradition set by the late Franz Halberg, highlights of research
      performed over the last year from his Minnesota Center are summarized. They
      illustrate the broad international cooperation enjoyed by his center and the
      diversity of applications of the discipline he founded. The results briefly
      summarized herein in the form of an annotated bibliography are a testimony that
      his legacy continues to live on and constitutes a tribute to his memory. 

PMID- 25945430
TI  - Hepatoblastoma in a 14 month-old female.
AB  - Hepatoblastoma (HB) is the most common malignant liver tumor in children.
      Complete surgical resection is the best treatment choice with a good prognosis in
      most cases. We present the case of a 14 month-old female patient was admitted to
      the pediatric surgery unit due to an abdominal mass localized in the right upper
      quadrant. The diagnosis retained was hepatoblastoma, so the patient underwent
      preoperative chemotherapy. The final size of the tumor permitted a complete
      surgical resection through a right subcostal incision enlarged to the left.
      Hepatoblastoma is the most common malignant liver tumor in children, more
      frequent in male than in female and typically presenting before 3 years of age as
      an abdominal mass found accidentally. Recent treatment strategies, consisting of
      chemotherapy combined with extensive surgery and in extreme cases liver
      transplantation, have improved the prognosis during the last years although HB's
      etiology and management are still subjects of debate. 

PMID- 25945431
TI  - Diaphragmatic hernia as a spontaneous sequela of a surgically-treated left
      infiltrating renal tumor: a case report.
AB  - A diaphragmatic hernia is a protrusion of abdominal structures within the
      thoracic cavity through a defect in the diaphragm, which can be either congenital
      or acquired. Diaphragmatic rupture, as a sequela following abdominal surgery, is
      rarely documented. Approximately 80% of the reported cases, the injury occurred
      on the left side. We discuss a case of a 37 year-old male who underwent a left
      nephrectomy with ipsilateral adrenalectomy and diaphragmatic resection, by direct
      reconstruction that developed the sequela of a diaphragmatic hernia. We chose a
      surgical transthoracic approach for herniation repair. 

PMID- 25945433
TI  - Posterior Reversible Encephalopathy Syndrome in late postpartum eclampsia.
AB  - Posterior Reversible Encephalopathy Syndrome (PRES) is a neurological
      complication associated with several medical conditions and it has been described
      in clinical findings of seizures, headache, vomiting, altered mental status, and
      visual changes and focal neurologic deficit, in conjunction with radiological
      findings of primarily posterior cerebral white matter edema of both cerebral
      hemispheres. PRES can develop in a wide array situations including pregnancy and
      postpartum in patients with or without symptoms and signs of eclampsia. A prompt
      diagnosis of PRES by magnetic resonance imaging and an immediate antihypertensive
      and anticonvulsant therapy can help to prevent serious complications. The
      clinical case presented deals with a 35 year-old pregnant woman whose history of
      eclampsia was observed after a cesarean section. 

PMID- 25945432
TI  - Unusual branching pattern of brachial artery - Embryological basis and
      clinicoanatomical insight.
AB  - Variations in the arterial pattern of upper limb are of colossal importance to
      the surgeons as they are liable to iatrogenic injuries. During routine dissection
      for undergraduate medical students, an anomaly of brachial artery was discovered.
      The brachial artery terminated at higher level into ulnar and radial artery. The
      common interosseus artery took origin arising from radial artery. The ulnar
      artery did not give any branches in the forearm. Both radial and ulnar artery
      displayed a superficial course in the forearm. The anatomical knowledge of these
      variations may be of great help for the clinicians in planning and conducting
      flap harvesting during reconstructive surgeries and in arteriography.

PMID- 25945434
TI  - Unremitting body odour: A case of Olfactory Reference Syndrome.
AB  - Olfactory reference syndrome (ORS) is a person's fear of exuding an offensive
      body odour which is not perceived by others. The objective of this case report is
      to highlight the challenges in diagnosing olfactory reference syndrome due to the
      lack of diagnostic criteria as well as its similarities to other psychiatric
      illnesses. We report a case of a young Chinese gentleman who was preoccupied with
      the belief that he had an offensive body odour which was not noticeable by others
      since the age of 10. As a result of this, he developed compulsive behaviour,
      social anxiety and avoidance, as well as depression. The patient had an array of
      psychiatric symptoms. He had symptoms which fulfilled criteria for obsessive
      compulsive disorder (OCD), delusional disorder somatic type, and social anxiety
      disorder. ORS remains a diagnostic challenge. Further studies are needed in this
      area for a better understanding of the disorder. 

PMID- 25945435
TI  - Terukazu Kawasaki (10 September 1936 - 13 May 2014).

PMID- 25945436
TI  - On the "pendulum" of bioethics.
AB  - According to a well-known philosopher, the life of ethics was saved, at the
      beginning of the 1970s, by medicine. The claim is based on the consideration that
      the questions then being posed by medicine were actual and dramatic, forcing
      ethicists and philosophers to abandon their mostly useless abstract speculations.
      Since the early years of the new century some authors have been harsh in their
      criticism of bioethics, accusing it not only of not "returning the favour" to
      medicine but also of seriously hindering medical practice and, above all,
      research, by subjecting them to unnecessary constraints. Some of the more
      restrictive and bureaucratic regulations have been relaxed over the years, to the
      extent that some authors suggest that the bioethics pendulum "is taking a swing
      to the permissive". There are nonetheless some fundamental principles and values
      that do not admit of concessions. Provided these are properly guaranteed, it is
      appropriate to simplify overly rigid regulations (such as those concerning
      consent to the use of health data) and allow research to achieve potentially
      useful results. 

PMID- 25945437
TI  - On akrasia and the "prevention paradox".
AB  - The term akrasia describes the behaviour of persons who knowingly and consciously
      act against their better judgement and is exemplified by various unhealthy
      lifestyle choices. Prevention should aim to provide guidance in the choice of
      lifestyle. While at the individual level this is best directed towards those who
      are at high risk, at a general population level it is preferable to target the
      higher numbers of individuals at low risk rather than the fewer high-risk
      subjects. This is the so-called "prevention paradox". From an ethical viewpoint
      it is important, when planning measures to maximise the benefits for the
      community, not to neglect individual subjects: the common good is created by
      promoting and making the most of the good of the individual. 

PMID- 25945438
TI  - Assessment of documentation of DSM-IV-TR Criteria A for diagnosis of
      schizophrenia in psychiatric unit, tertiary hospital, Malaysia.
AB  - OBJECTIVE: The purposes of this study were to investigate the documentation of
      the DSM-IV-TR- Criteria A in diagnoses of schizophrenia and to identify the
      symptoms associated with over diagnosis of schizophrenia. METHOD: This study
      involved a retrospective review and analysis of data from case notes. RESULTS:
      Data of 107 newly diagnosed patients with schizophrenia were keyed in and
      analyzed using SPSS v 19. The cases were then evaluated for the use of the DSM-IV
      TR- Criteria A. Over diagnosis was noted in 37.39% of the patients. Disorganised
      behaviour (12.5%), affective flattening (12.5%), hallucination (16%) and non
      bizarre delusion (18.3%) significantly contributed to the over-diagnosis of
      schizophrenia. Symptoms such as non-bizarre delusion and hallucination were the
      most commonly used in over-diagnosing schizophrenia and were statistically
      significant with p <=0.05. CONCLUSIONS: There was a significant lack of DSM-IV-TR
      Criteria A among the data documented to diagnose schizophrenia and non-bizarre
      delusion and hallucination were the most commonly used in over-diagnosing
      schizophrenia. This key problem needs to be addressed. The reliability of a
      diagnosis is indispensable and achievable with the proper clinical application of
      DSM-IV-TR Criteria A. The DSM-IV-TR Criteria have been perceived to be useful and
      reliable and is most widely used throughout the world.

PMID- 25945439
TI  - White gauze test: a novel technique in preventing post-hepatectomy bile leak.
AB  - BACKGROUND: Post-hepatectomy bile leak may lead to undesired morbidity. Multiple
      methods have been employed to identify this leak but can be inconclusive and
      taxing. This novel white gauze test is a simple and reliable method. MATERIALS
      AND METHODS: This is a prospective study performed from January 2010 until March
      2011. All open hepatic resection were included. Dry white gauze is compressed
      onto the transected surface and observed for bile staining. The leaking duct is
      repaired immediately upon detection. The process is repeated until negative.
      Drain was removed on postoperative day-5. Post-operative bile leak is defined as:
      1. Bilirubin concentration of the drain fluid is 3 times or higher than serum; 2.
      Presence of intra-abdominal bile collection on imaging and upon drainage; 3. Bile
      leak demonstrated on postoperative cholangiography. RESULTS: 42 patients were
      recruited. Seven (16.7%) patients were cirrhotic with Child-Pugh A. White gauze
      test were positive for intra-operative bile leaks in 29 patients (70%), which
      were primarily repaired. As a result, there was no postoperative bile leak in
      this series. One mortality was detected in this series due to postoperative
      pancreatic fistula and multi organ failure. CONCLUSIONS: The White Gauze Test is
      a useful method for the prevention of bile leakage after hepatic resection. It is
      safe, quick and cheap.

PMID- 25945440
TI  - Appendicitis and abscess in an adult patient with intestinal nonrotation: Case
      report.
AB  - The aim of the article is showing a particular case of midgut nonrotation. It is
      a congenital defect of the bowel development, during which fails the rotation of
      270 degrees  around the vascular pedicle. This anomaly causes a different
      intestinal arrangement: the small bowel is located in the right side of abdominal
      cavity while the large bowel is situated in the left side. We present a case of
      acute appendicitis and abscess treated successfully with urgent surgical
      intervention in a patient completely asymptomatic for nonrotation. Nonrotation
      may lead to acute symptoms, vague abdominal pain or may remain asymptomatic
      throughout all life and be discovered only accidentally. Radiological exams and
      laparoscopy can help to make a correct diagnosis. A conservative treatment could
      be preferred in asymptomatic patients and Ladd's surgical procedure should be
      performed in selected cases.

PMID- 25945441
TI  - Early right hepatectomy for severe liver trauma: a case report.
AB  - Liver is frequently involved and injured in blunt abdominal trauma. Although over
      the last three decades the management of blunt hepatic trauma has gradually
      shifted toward nonoperative approach whit a significant reduction in overall
      mortality, surgery remains the main option for hemodinamically unstable patients
      whit severe liver injuries. A 16-yr-old male in good health suffered a blunt
      abdominal trauma from a sport accident falling while playing football resulting
      in a grade V liver injury according to the American Association for the Surgery
      of Trauma Organ Injury Score. He underwent first to liver packing and next to an
      early right hepatectomy to arrest the clinical condition impairment In high grade
      liver injuries, liver resection makes possible to effectively control bleeding,
      remove necrotic tissue and prevent complications as bile leak. Nevertheless when
      patient's clinical condition continue to deteriorate despite optimal management a
      quickly and experienced hands performed hepatectomy may solve the situation.

PMID- 25945442
TI  - Spontaneous Bilateral Adrenal Haemorrhage after Duodenopancreatectomy: a case
      report.
AB  - it is difficult to diagnose because of its nonspecific presentation. This
      condition frequently occurs in association with an extreme physical stress and
      may lead to acute adrenal insufficiency or death if not promptly and properly
      treated. We report a rare case of acute bilateral adrenal hemorrhage with adrenal
      insufficiency following duodenopancreatectomy for ampulloma in absence of
      surgical complications. Early diagnosis and corticosteroid replacement with
      aggressive management of the precipitating pathology are essential to enable a
      successful outcome.

PMID- 25945443
TI  - Alpha chemokines in Crohn's disease.
AB  - Many studies have shown that chemokine (C-X-C motif) receptor (CXCR)3 and its
      ligand chemokines, as monokine induced by interferon (IFN)-gamma (MIG),
      interferon-gamma inducible protein (IP-10) and IFN-inducible T cell-alpha
      chemoattractant (I-TAC), are strongly overexpressed both in the intestinal mucosa
      of mice with experimental colitis, and in patients with Crohn's disease (CD) in
      lymphocytes, in macrophages and in epithelial cells. IFN-gamma induces CXCR3 and
      its chemokines expression in epithelial intestinal cells; these chemokines are
      important for the recruitment of granulocytes and mononuclear cells, thus for the
      maintenance of inflammation in CD. Serum IP-10 levels might reflect CD disease
      activity, and it may be a marker for the responsiveness of patients to
      treatments. However other studies are needed to document the use of IP-10 in
      clinical setting. Attempts are currently underway to inhibit CXCR3 or its
      chemokines in CD as a possible therapy of CD.

PMID- 25945444
TI  - Dermatomyositis and chemokines.
AB  - Abundant expression of IFN-gamma-inducible protein 10 (IP-10) was observed on
      macrophages and in T cells in perimysial infiltrates of dermatomyositis (DM), and
      strong chemokine (C-X-C motif) receptor (CXCR)3 expression was observed on the
      majority of T cells in DM. This suggests that the T helper (Th)1-mediated
      immunity in general, and the CXCR3/IP-10 interaction in particular, is important
      in the immunopathogenesis of DM. The study of infiltrating cells, related
      cytokines and chemokine receptors in lesional skin of patients with DM, confirmed
      the importance of Th1 chemokines. Type I Interferon chemokines, and overall IP
      10, are tightly linked to active disease and are correlated with the clinical
      score in juvenile DM, thus could be helpful in monitoring disease activity and
      guiding treatment.

PMID- 25945445
TI  - Th1 cytokines and chemokines in primary biliary cirrhosis.
AB  - T- helper 1 (Th1) cytokines and chemokines in primary biliary cirrhosis (PBC) has
      been investigated in several studies. The involvement of (C-X-C motif) receptor 3
      (CXCR3) and its ligands in the pathogenesis of PBC was studied in autoimmune
      cholangitis animal models suggesting that CXCR3 chemokines contribute to the
      development of PBC. In humans with PBC, interferon (IFN)gamma-induced protein 10
      (IP-10) and chemokine (C-X-C motif) ligand 9 (MIG) expressions, and CXCR3
      positive cells were present in the portal areas of diseased livers. MIG and IP-10
      were positively associated with the severity of liver fibrosis. Circulating IP-10
      and MIG levels, and CXCR3-expressing cells, in PBC were increased significantly
      compared to controls and appeared to increase with disease progression.
      Furthermore, a significant reduction of these chemokines in PBC patients' serum
      after ursodeoxycholic acid (UDCA) treatment has been shown.

PMID- 25945447
TI  - [Necrotizing Fasciitis: A comprehensive review].
AB  - Even though necrotizing fasciitis is considered a rare disease, the spreading of
      the predisposing factors such as diabetes and chronic diseases, contribute to
      increase the incidence of this infection. Thus, how to diagnose and treat this
      clinical pathology, which represents an emerging need. This infection could be
      fatal for patients if not early diagnosed and treated and it represents a
      challenge both for the clinicians both for the surgeons. From this consideration
      was born the idea to write this review article in order to furnish to the readers
      a helpful tool in the management of this disease starting from its clinical and
      epidemiological features leading to the diagnosis, both clinical and
      radiological, and concluding with the treatment both medical both surgical .This
      article reviews literature on PubMed/MEDLINE with key words "necrotizing",
      "fasciitis" and "necrotizing fasciitis" from 1967 to 2014, considering all the
      aspects of the disease. The authors attempt to draw comparisons to their own
      experience managing this condition to give an Italian perspective to the
      condition.

PMID- 25945446
TI  - Th1 chemokines in ulcerative colitis.
AB  - Many studies have shown that chemokine (C-X-C motif) receptor (CXCR)3 (a
      chemokine receptor in the CXC family) and its ligand chemokines, monokine induced
      by interferon (IFN)-gamma(MIG), IFN-gamma-inducible protein 10 (IP-10) and IFN
      inducible T-cell alpha chemoattractant (I-TAC), are strongly overexpressed in the
      intestinal mucosa of mice with experimental colitis, and in patients with
      ulcerative colitis (UC) both in lymphocytes, in macrophages and in epithelial
      cells. IFN-gamma induces CXCR3 and its chemokines expression in epithelial
      colonic cells; MIG, IP-10 and I-TAC are important for the recruitment of
      granulocytes and mononuclear cells and thus for the maintenance of inflammation
      in UC. Serum IP-10 levels reflected UC disease activity, and it may be a marker
      for the responsiveness of patients to treatments. Recently, a phase II study
      suggested that an anti-IP-10 antibody, BMS-936557, is a potentially effective
      therapy for moderately-to-severely active UC.

PMID- 25945448
TI  - Early diagnosis of hearing loss: otoacoustic emissions evoked by distortion
      products and pure-tone audiometry: Preliminary findings.
AB  - OBJECTIVE: Literary studies underline the effectiveness of distortion product
      otoacoustic emissions (DPOAEs), which are not affected by the collaboration of
      the subject examined, in the early diagnosis of hearing loss. Aim of the study is
      to compare the objective technique of DPOAEs with respect to the pure-tone
      audiometry in early diagnosis of hearing loss. MATERIALS AND METHODS: The
      clinical research was carried out on 852 workers. All subjects underwent pure
      tone audiometry, tympanometry and distortion products. RESULTS: The results show:
      a) a prevalence of subjects with impaired DPOAEs higher than the prevalence of
      subjects with impaired audiometries in the studied samples; and, after division
      by gender: b) a prevalence of subjects with impaired DPOAEs higher than the
      prevalence of subjects with impaired audiometries only in men; c) a prevalence of
      impaired DPOAEs and of impaired audiometries in men higher than in women.
      CONCLUSIONS: The results suggest the higher effectiveness of DPOAEs compared to
      pure-tone audiometry in making an early diagnosis of hearing loss.

PMID- 25945449
TI  - Tocotrienol-rich fraction prevents cellular aging by modulating cell
      proliferation signaling pathways.
AB  - BACKGROUND AND OBJECTIVE: Vitamin E has been suggested as nutritional
      intervention for the prevention of degenerative and age-related diseases. In this
      study, we aimed to elucidate the underlying mechanism of tocotrienol-rich
      fraction (TRF) in delaying cellular aging by targeting the proliferation
      signaling pathways in human diploid fibroblasts (HDFs). MATERIALS AND METHODS:
      Tocotrienol-rich fraction was used to treat different stages of cellular aging of
      primary human diploid fibroblasts viz. young (passage 6), pre-senescent (passage
      15) and senescent (passage 30). Several selected targets involved in the
      downstream of PI3K/AKT and RAF/MEK/ERK pathways were compared in total RNA and
      protein. RESULTS: Different transcriptional profiles were observed in young, pre
      senescent and senescent HDFs, in which cellular aging increased AKT, FOXO3,
      CDKN1A and RSK1 mRNA expression level, but decreased ELK1, FOS and SIRT1 mRNA
      expression level. With tocotrienol-rich fraction treatment, gene expression of
      AKT, FOXO3, ERK and RSK1 mRNA was decreased in senescent cells, but not in young
      cells. The three down-regulated mRNA in cellular aging, ELK1, FOS and SIRT1, were
      increased with tocotrienol-rich fraction treatment. Expression of FOXO3 and
      P21Cip1 proteins showed up-regulation in senescent cells but tocotrienol-rich
      fraction only decreased P21Cip1 protein expression in senescent cells.
      CONCLUSIONS: Tocotrienol-rich fraction exerts gene modulating properties that
      might be responsible in promoting cell cycle progression during cellular aging.

PMID- 25945450
TI  - [Comparison of diagnostic quality in hysterosalpingography between iodinated non
      ionic contrast media with low and high osmolarity].
AB  - PURPOSE: Comparison of diagnostic quality in hysterosalpingography between low
      and high-osmolality contrast media. MATERIALS AND METHODS: We performed a
      retrospective evaluation of two cohorts of patients who underwent HSG using
      contrast media with different osmolarity: the first group ,47 patients, underwent
      hysterosalpingography in the period September 2011-December 2012 using Iopromide
      370 mg/ml; the second group, 50 patients, underwent HSG from January 2013 to
      October 2013 using Iomeprol 400 mg/ml. Three radiologists, in consensus reading,,
      reviewed the radiographs by assessing the following four parameters:
      opacification of the uterine cavity, uterine profiles definition, Fallopian tubes
      visualization, contrast media spillage into peritoneum. A score-scale from 0 to 3
      was assigned for each of the mentioned parameter (0 = minimum non-diagnostic
      exam, 1 = sufficient examination; 2 = good quality examination; maximum 3 = high
      quality images). RESULTS: We documented a statistically significant higher
      quality in displaying Fallopian tubes among patients studied through high
      osmolarity contrast medium (Iopromide 370 mg/ml) than what obtained through lower
      osmolarity contrast medium (Iomeprol 400 mg/ml). CONCLUSIONS: The use of high
      osmolarity contrast medium enabled better visualization of the tubes and a
      greater number of diagnoses of chronic aspecific salpigintis due to the increased
      osmolality and viscosity of Iomeprol 400 mg/ml. There were no significant
      differences between the two contrast agents in the evaluation of intra-uterine
      pathology and in the evaluation of the tubal patency.

PMID- 25945451
TI  - Antinuclear Antibodies predict a higher number of Pregnancy Loss in Unexplained
      Recurrent Pregnancy Loss.
AB  - OBJECTIVE: The etiology of recurrent pregnancy loss (RPL) is unknown in a
      significant proportion of patients. Autoimmune processes have been implicated in
      the pathogenesis. The role of antinuclear antibody (ANA) in this context is
      largely undetermined. In an attempt to address the lack of evidence in this area,
      we explored the clinical significance of antinuclear antibody (ANA) in
      unexplained RPL. MATERIALS AND METHODS: We studied 68 patients with RPL and 60
      healthy controls from September 2005 to May 2012. All subjects were tested for
      ANA by immunofluorescence testing, and a titer of 1: 80 and above was considered
      positive. We compared the pregnancy outcome between the ANA positive and ANA
      negative RPL cases. RESULTS: The incidence of ANA positivity among the cases
      (35.3%) was significantly higher than the controls (13.3%) (p=0.005). ANA
      positive cases showed significantly higher number of RPL (p=0.006) and lower
      number of successful pregnancies (p=0.013) compared to the ANA negative cases .
      The ANA titre had a significant association with the number of RPL (p<0.05,
      r=0.724) but not with the number of successful pregnancies (p=0.054).
      CONCLUSIONS: ANA positivity predicts a less favorable pregnancy outcome in RPL.
      Our findings suggest that the ANA titre is a useful positive predictor of the
      number of RPL. Hence, ANA test is a potential prognostic tool for this condition
      which merits further research.

PMID- 25945452
TI  - Urban washout: how strong is the rural-background effect?
AB  - OBJECTIVE: To test predictors of practice location of fully qualified Monash
      University Bachelor of Medicine, Bachelor of Surgery (MBBS) graduates. DESIGN:
      Cohort survey, 2011. SETTING: Australia. PARTICIPANTS: Rural (n = 67/129) and
      urban (n = 86/191) background doctors starting at Monash University 1992-1999.
      Approximately 60% female, 77% married/partnered, 79% Australian-born, mean age 34
      years, 31% general practitioners, 72% fully qualified and 80% training/practising
      in major cities. MAIN OUTCOME MEASURES: First and current practice location once
      fully qualified. Intended practice location in 5-10 years. RESULTS: Logistic
      regression found that rural versus urban background was a significant predictor
      of rural (outside major city) first practice location (odds ratio (OR) 5.0, 95%
      confidence interval (CI) 1.3-19.2) and rural current practice location (OR 5.6,
      95% CI 1.5-21.2) for fully qualified doctors. General practitioner versus other
      medical specialists significantly predicted first (OR 7.2, 95% CI 2.1-25.2) or
      current (OR 3.6, 95% CI 1.1-11.9) rural practice location. Preference for a rural
      practice location in 5-10 years was predicted by rural background (OR 4.4, 95% CI
      1.6-11.8) and positive intention towards rural practice upon completing MBBS (OR
      4.6, 95% CI 1.7-12.6). Surveyed in 2011, 28% of those who also responded to the
      2006 survey shifted their preferred future practice location from rural to urban
      communities versus 13% shifting from urban to rural (McNemar-Bowker test, P =
      0.02). CONCLUSION: The majority of fully qualified Monash MBBS graduates
      practicing in rural communities have rural backgrounds. The rural-background
      effect diminished over time and may need continued support during training and
      full practice.

PMID- 25945453
TI  - Does a Reduction in Serum Sodium Concentration or Serum Potassium Concentration
      Increase the Prevalence of Exercise-Associated Muscle Cramps?
AB  - CLINICAL SCENARIO: Although exercise-associated muscle cramps (EAMC) are common
      in ultradistance runners and athletes in general, their etiology remains unclear.
      EAMC are painful, sudden, involuntary contractions of skeletal muscle occurring
      during or after exercise and are recognized by visible bulging or knotting of the
      whole, or part of, a muscle. Many clinicians believe EAMC occur after an
      imbalance in electrolyte concentrations, specifically serum sodium concentration
      ([Na+]s) and serum potassium concentration ([K+]s). Studies that have established
      a link between EAMC occurrence and serum electrolyte concentrations after an
      athletic event are unhelpful. Focused Clinical Question: Are [Na+]s and [K+]s
      different in athletes who experience EAMC than noncrampers?

PMID- 25945454
TI  - Broadening the spectrum of Catania brachydactylous type of acrofacial dysostoses.

PMID- 25945455
TI  - Sacrococcygeal appendage with femur: exoparasitic pyropagus twin, mature
      teratoma, or disorganization-like syndrome?

PMID- 25945456
TI  - Hypothyroidism due to Hashimoto's thyroiditis masked by anorexia nervosa.
AB  - Anorexia nervosa (AN) is typically associated with altered thyroid function
      tests, notably a low total and free T3 , and lower, but within normal range, free
      T4 and TSH. A 16-year-old girl with a four-year history of AN presented with
      elevated TSH that fluctuated with changes in weight. TSH was within normal limits
      (1.7-3.64 mIU/L) following periods of weight loss and elevated with weight gain
      (5.9-21.66 mIU/L). Antithyroperoxidase antibodies were markedly elevated,
      suggesting chronic Hashimoto's thyroiditis. Of note, the elevated TSH that would
      be expected in Hashimoto's thyroiditis was blunted by weight loss associated with
      AN. Physicians should be aware that AN may contribute to masking thyroid
      abnormalities in Hashimoto's thyroiditis.

PMID- 25945457
TI  - Fifty Years of the Best of Investigative Radiology.

PMID- 25945458
TI  - T1-Weighted Contrast-Enhanced Magnetic Resonance Imaging of the Small Bowel:
      Comparison Between 1.5 and 7 T.
AB  - OBJECTIVES: T1-weighted (T1w) contrast-enhanced magnetic resonance imaging (MRI)
      of the small bowel at 1.5 T magnetic field strength has become a standard
      technique in investigating diseases of the small bowel. High-field MRI
      potentially offers improved soft tissue contrast and spatial resolution,
      providing increased image detail. The purpose of this study was to evaluate the
      feasibility of contrast-enhanced small bowel MRI at 7 T and to compare results
      with 1.5 T. MATERIALS AND METHODS: Twelve healthy volunteers underwent small
      bowel MRI on a 1.5 T and 7 T MRI system. A coronal fat-saturated T1w spoiled
      gradient-echo sequence (3-dimensional [3D] FLASH) was applied precontrast and at
      20 seconds, 75 seconds, and 120 seconds after intravenous contrast
      administration. Furthermore, late-phase coronal and axial fat-saturated T1w 2
      dimensional (2D) FLASH data sets were acquired. Visual evaluation of tissue
      contrast and image detail of the small bowel wall and mesentery as well as
      contrast ratios were compared between 1.5 T and 7 T in an intraindividual
      comparison. In addition, subjective ratings of image impairment by artifacts were
      assessed at both field strengths. RESULTS: Magnetic resonance imaging of the
      small bowel at 7 T revealed equal tissue contrast and image detail compared with
      1.5 T. Higher contrast and improved image detail of mesentery structures at 7 T
      were found in nonenhanced 3D FLASH. Quantitatively measured contrast between the
      bowel wall and bowel lumen showed significantly lower contrast at 7 T in
      nonenhanced 3D FLASH and in late-phase 2D FLASH. Image quality was more impaired
      at 7 T compared with 1.5 T, mainly due to increased susceptibility artifacts and
      B1 inhomogeneities. CONCLUSIONS: T1-weighted contrast-enhanced MRI of the small
      bowel at 7 T represents a promising MR technique for establishing ultra-high
      magnetic field strengths in clinical applications. Despite increased artifacts at
      7 T, depiction of the small bowel was achieved with comparable quality to the
      current state-of-the-art field strength of 1.5 T. Assessment of potential
      diagnostic benefits should be the focus of future high-field MRI studies.

PMID- 25945459
TI  - Isolation and characterization of living circulating tumor cells in patients by
      immunomagnetic negative enrichment coupled with flow cytometry.
AB  - BACKGROUND: This study was aimed at establishing a sensitive and specific
      isolation, characterization, and enumeration method for living circulating tumor
      cells (CTCs) in patients with colorectal carcinoma. METHODS: Quantitative
      isolation and characterization of CTCs were performed through a combination of
      immunomagnetic negative enrichment and fluorescence-activated cell sorting.
      Isolated CTCs were identified by immunofluorescence staining. The viability and
      purity of the sorted cells were determined by flow cytometry. Blood samples
      spiked with HCT116 cells (range, 3-250 cells) were used to determine specificity,
      recovery, and sensitivity. The method was used to enumerate, characterize, and
      isolate living CTCs in 10 mL of blood from patients with colorectal carcinoma.
      RESULTS: The average recovery of HCT116 cells was 61% or more at each spiking
      level, and the correlation coefficient was 0.992. An analysis of samples from all
      18 patients with colorectal carcinoma revealed that 94.4% were positive for CTCs
      with an average of 33 +/- 24 CTCs per 10 mL of blood and with a diameter of 14 to
      20 MUm (vs 8-12 MUm for lymphoma). All patients were CD47(+) , with only 4.3% to
      61.2% being CD44(+) . The number of CTCs was well correlated with the patient TNM
      stage and could be detected in patients at an early cancer stage. The sorted
      cells could be recultured, and their viability was preserved. CONCLUSIONS: This
      method provides a novel technique for highly sensitive and specific detection and
      isolation of CTCs in patients with colorectal carcinoma. This method complements
      the existing approaches for the de novo functional identification of a wide
      variety of CTC types. It is likely to help in predicting a patient's disease
      progression and potentially in selecting the appropriate treatment.

PMID- 25945461
TI  - A Poly(9-Borafluorene) Homopolymer: An Electron-Deficient Polyfluorene with "Turn
      On" Fluorescence Sensing of NH3 Vapor.
AB  - A substituted poly(9-borafluorene) (P9BF) homopolymer, a boron congener of
      polyfluorene, is prepared by Yamamoto coupling of a triisopropylphenyl
      substituted borafluorene (1). As predicted by prior density functional theory
      (DFT) studies, P9BF has a reduced optical bandgap (Eg,opt = 2.28 eV) and a
      significantly lowered LUMO level (-3.9 eV, estimated by cyclic voltammetry (CV))
      compared to polyfluorene. In addition to binding fluoride in solution, films of
      P9BF exhibit a reversible, simultaneous turn-off/turn-on fluorescence response to
      NH3 vapor. A 9-borafluorene-vinylene copolymer (P9BFV) is synthesized via Stille
      coupling, demonstrating that 1 can readily be incorporated into copolymers. The
      extended conjugation of P9BFV due to the inclusion of the vinylene group results
      in a reduced optical bandgap (2.12 eV) and LUMO (-4.0 eV, estimated by CV)
      compared to the homopolymer P9BF. 

PMID- 25945460
TI  - LW-213 induces G2/M cell cycle arrest through AKT/GSK3beta/beta-catenin signaling
      pathway in human breast cancer cells.
AB  - LW-213 is a derivative of Wogonin and the anticancer activities of Wogonin have
      been reported. To study whether LW-213 inhibits cancer cells and explore a
      possible mechanism, we investigate the compound in several cancer cell lines. We
      found LW-213 arrests G2/M cycle in breast cancer cells by suppression of
      Akt/Gsk3beta/beta-catenin signaling pathway. In compound treated cells, cell
      cycle-related proteins cyclin A, cyclin B1, p-CDK1, p-Cdc25C, and p-Chk2 (Thr68)
      were upregulated, and beta-catenin nuclear translocation was inhibited.
      Electrophoretic mobility shift assay revealed LW-213 inhibits binding of beta
      catenin/LEF complex to DNA. GSK3beta inhibitor LiCl and siRNA against GSK3beta
      partially reversed G2/M arrest in breast cancer MCF-7 cells. These results
      suggest LW-213 triggered G2/M cell cycle arrest through suppression of beta
      catenin signaling. In BALB/c mice, growth of xenotransplanted MCF-7 tumor was
      also inhibited after treatment of LW-213. Regulation of cyclin A, cyclin B1, and
      beta-catenin by LW-213 in vivo was the same as in vitro study. In conclusion, we
      found LW-213 exerts its anticancer effect on cell proliferation and cell cycle
      through repression of Akt/Gsk3beta/beta-catenin signaling pathway. LW-213 could
      be a potential candidate for anticancer drug development.

PMID- 25945462
TI  - Vitamin B12 catalysed reactions.
AB  - Vitamin B12 (cobalamin, 1) is one of a few naturally occurring organometallic
      molecules. As a cofactor for adenosylcobalamin-dependent and methylcobalamin
      dependent enzymes, it plays a crucial role in biological processes, including DNA
      synthesis and regulation, nervous system function, red blood cell formation, etc.
      Enzymatic reactions, such as isomerisation, dehalogenation, and methyl transfer,
      rely on the formation and cleavage of the Co-C bond. Because it is a natural,
      nontoxic, environmentally benign cobalt complex, cobalamin (1) has been
      successfully utilised in organic synthesis as a catalyst for Co-mediated
      reactions. This tutorial review concisely describes cobalamin-catalysed organic
      reactions that hold promise for environmentally friendly cobalt catalysis,
      leaving the reader with basic knowledge and the ability to harness the catalytic
      potential of this fascinating molecule.

PMID- 25945466
TI  - Nobel prizes: contributions to cardiology.
AB  - The Nobel Prize was created by Alfred Nobel. The first prize was awarded in 1901
      and Emil Adolf von Behring was the first laureate in medicine due to his research
      in diphtheria serum. Regarding cardiology, Nobel Prize's history permits a global
      comprehension of progress in pathophysiology, diagnosis and therapeutics of
      various cardiac diseases in last 120 years. The objective of this study was to
      review the major scientific discoveries contemplated by Nobel Prizes that
      contributed to cardiology. In addition, we also hypothesized why Carlos Chagas,
      one of our most important scientists, did not win the prize in two occasions. We
      carried out a non-systematic review of Nobel Prize winners, selecting the main
      studies relevant to heart diseaseamong the laureates. In the period between 1901
      and 2013, 204 researches and 104 prizes were awarded in Nobel Prize, of which 16
      (15%) studies were important for cardiovascular area. There were 33 (16%)
      laureates, and two (6%) were women. Fourteen (42%) were American, 15 (45%)
      Europeans and four (13%) were from other countries. There was only one winner
      born in Brazil, Peter Medawar, whose career was all in England. Reviewing the
      history of the Nobel Prize in physiology or medicine area made possible to
      identify which researchers and studies had contributed to advances in the
      diagnosis, prevention and treatment of cardiovascular diseases. Most winners were
      North Americans and Europeans, and male. 

PMID- 25945469
TI  - Treatment of a double-giant Rhinophyma with electrocautery and Versajet
      hydrosurgery system.
AB  - Rhinophyma is a disfiguring condition etiologically related to rosacea and due to
      hypertrophy of the sebaceous glands of the nose. It leads to a progressive
      thickening of the skin up to the development, in some cases, of severe
      deformities that result in significant functional deficits and serious cosmetic
      damage. We report a case of giant rhinophyma consisting of 2 large masses that
      interfered with feeding and respiration of the patient, and we describe the
      surgical treatment by resection with electrosurgery and razor-thin saline jet
      (Versajet Hydrosurgery System). This combined approach is simple and effective
      for the treatment of severe cases of rhinophyma.

PMID- 25945470
TI  - Inner ear deficits in irradiated nasopharyngeal carcinoma survivors.
AB  - OBJECTIVES/HYPOTHESIS: Despite the advancement of concurrent chemoradiotherapy,
      inner ear symptoms such as hearing loss, tinnitus, or vertigo/dizziness are still
      experienced in irradiated nasopharyngeal carcinoma (NPC) survivors. This study
      utilized an inner ear test battery to assess the causes and sequence of inner ear
      deficits in irradiated NPC survivors with a mean interval of 10 years after
      radiotherapy. STUDY DESIGN: Retrospective study. METHODS: Thirty-six irradiated
      NPC survivors were enrolled. Otoscopy and an inner ear test battery comprising
      audiometry were performed, as well as ocular vestibular-evoked myogenic potential
      (oVEMP), cervical VEMP (cVEMP), and caloric tests. RESULTS: Otoscopic examination
      revealed middle ear complications in 37 ears (51%), including radiation-induced
      otitis media in 32 ears and otitis media with effusion in five ears. Percentages
      of abnormal cVEMP test, oVEMP test, bone-conducted mean hearing level, and
      caloric test were 91%, 75%, 67%, and 39%, respectively, exhibiting a
      significantly declining sequence in inner ear deficits. Most (67%) NPC survivors
      had inner ear deficit originated from peripheral vestibular lesion, mainly due to
      sequela of otitis media. In contrast, 33% of them had inner ear deficit caused by
      central vestibular disorder. CONCLUSIONS: A significant sequential decline in
      inner ear function of irradiated NPC survivors was observed from the saccule to
      the utricle, cochlea, and semicircular canals. Most of them were due to sequela
      of otitis media, followed by central vestibular disorder. LEVEL OF EVIDENCE: 4.

PMID- 25945468
TI  - Role of histological findings and pathologic diagnosis for detection of human
      papillomavirus infection in men.
AB  - Early HPV infection in males is difficult to detect clinically and
      pathologically. This study assessed histopathology in diagnosing male genital
      HPV. External genital lesions (n = 352) were biopsied, diagnosed by a
      dermatopathologist, and HPV genotyped. A subset (n = 167) was diagnosed
      independently by a second dermatopathologist and also re-evaluated in detail,
      tabulating the presence of a set of histopathologic characteristics related to
      HPV infection. Cases that received discrepant diagnoses or HPV-related diagnoses
      were evaluated by a third dermatopathologist (n = 163). Across
      dermatopathologists, three-way concordance was fair (k = 0.30). Pairwise
      concordance for condyloma was fair to good (k = 0.30-0.67) and poor to moderate
      for penile intraepithelial neoplasia (k = -0.05 to 0.42). Diagnoses were 44-47%
      sensitive and 65-72% specific for HPV 6/11-containing lesions, and 20-37%
      sensitive and 98-99% specific for HPV 16/18. Presence of HPV 6/11 was 75-79%
      sensitive and 35% specific for predicting pathologic diagnosis of condyloma. For
      diagnosis of penile intraepithelial neoplasia, HPV 16/18 was 95-96% specific but
      only 40-64% sensitive. Rounded papillomatosis, hypergranulosis, and dilated
      vessels were significantly (P < 0.05) associated with HPV 6/11. Dysplasia was
      significantly (P = 0.001) associated with HPV 16/18. Dermatopathologists'
      diagnoses of early male genital HPV-related lesions appear discordant with low
      sensitivity, while genotyping may overestimate clinically significant HPV-related
      disease. Rounded papillomatosis, hypergranulosis, and dilated vessels may help
      establish diagnosis of early condyloma.

PMID- 25945472
TI  - Educational Objectives/Credit Hours.

PMID- 25945473
TI  - Nurses Sessions.

PMID- 25945475
TI  - Index to Session Chairs.

PMID- 25945474
TI  - Annual Lecturers.

PMID- 25945478
TI  - Council of AsMA.

PMID- 25945477
TI  - Past Presidents of AsMA.

PMID- 25945476
TI  - Exhibits & Map.

PMID- 25945480
TI  - Headquarters Staff Photos.

PMID- 25945479
TI  - Wing Board of Directors.

PMID- 25945481
TI  - Bylaws of the Aerospace Medical Association.

PMID- 25945482
TI  - Inferior frontal gyrus white matter abnormalities in obsessive-compulsive
      disorder.
AB  - The aim of the present study is to explore obsessive-compulsive disorder (OCD)
      related abnormalities in white matter connectivity in OCD for a core region
      associated with inhibitory control [i.e. inferior frontal gyrus (IFG)]. Fifteen
      patients with OCD (11 men) and 15 healthy controls (nine men) underwent diffusion
      tensor imaging scanning to study four diffusivity indexes of white matter
      integrity [fractional anisotropy, mean diffusivity (MD), axial diffusivity and
      radial diffusivity (RD)]. The results showed that persons with OCD manifested
      significantly lower fractional anisotropy levels in the bilateral IFG as well as
      its parcellations in the pars opercularis, pars triangularis, and pars orbitalis.
      Significantly higher levels of MD, RD were evident for the OCD group in the IFG
      as a whole as well as in the bilateral subregions of the pars triangularis and
      pars opercularis (for MD and RD), the right side of the pars orbitalis (for RD),
      and the left side of the pars triangularis and right side pars opercularis (for
      axial diffusivity). Overall, the results suggest significant alterations in
      structural connectivity, probably associated with myelination and axonal
      abnormalities in the IFG of OCD patients.

PMID- 25945485
TI  - Anti-inflammatory Intervention in Depression.

PMID- 25945486
TI  - Anti-inflammatory Intervention in Depression.

PMID- 25945487
TI  - Anti-inflammatory Intervention in Depression.

PMID- 25945488
TI  - Anti-inflammatory Intervention in Depression--Reply.

PMID- 25945489
TI  - Measuring the effects of treatment with antipsychotics.

PMID- 25945490
TI  - Measuring the effects of treatment with antipsychotics.

PMID- 25945491
TI  - Measuring the effects of treatment with antipsychotics.

PMID- 25945492
TI  - Measuring the effects of treatment with antipsychotics--reply.

PMID- 25945493
TI  - Long-Term Safety of Repeated Blood-Brain Barrier Opening via Focused Ultrasound
      with Microbubbles in Non-Human Primates Performing a Cognitive Task.
AB  - Focused Ultrasound (FUS) coupled with intravenous administration of microbubbles
      (MB) is a non-invasive technique that has been shown to reliably open (increase
      the permeability of) the blood-brain barrier (BBB) in multiple in vivo models
      including non-human primates (NHP). This procedure has shown promise for clinical
      and basic science applications, yet the safety and potential neurological effects
      of long term application in NHP requires further investigation under parameters
      shown to be efficacious in that species (500 kHz, 200-400 kPa, 4-5 MUm MB, 2
      minute sonication). In this study, we repeatedly opened the BBB in the caudate
      and putamen regions of the basal ganglia of 4 NHP using FUS with systemically
      administered MB over 4-20 months. We assessed the safety of the FUS with MB
      procedure using MRI to detect edema or hemorrhaging in the brain. Contrast
      enhanced T1-weighted MRI sequences showed a 98% success rate for openings in the
      targeted regions. T2-weighted and SWI sequences indicated a lack edema in the
      majority of the cases. We investigated potential neurological effects of the FUS
      with MB procedure through quantitative cognitive testing of' visual, cognitive,
      motivational, and motor function using a random dot motion task with reward
      magnitude bias presented on a touchpanel display. Reaction times during the task
      significantly increased on the day of the FUS with MB procedure. This increase
      returned to baseline within 4-5 days after the procedure. Visual motion
      discrimination thresholds were unaffected. Our results indicate FUS with MB can
      be a safe method for repeated opening of the BBB at the basal ganglia in NHP for
      up to 20 months without any long-term negative physiological or neurological
      effects with the parameters used.

PMID- 25945495
TI  - Correction: The Cricket Paralysis Virus Suppressor Inhibits microRNA Silencing
      Mediated by the Drosophila Argonaute-2 Protein.

PMID- 25945494
TI  - PERK Limits Drosophila Lifespan by Promoting Intestinal Stem Cell Proliferation
      in Response to ER Stress.
AB  - Intestinal homeostasis requires precise control of intestinal stem cell (ISC)
      proliferation. In Drosophila, this control declines with age largely due to
      chronic activation of stress signaling and associated chronic inflammatory
      conditions. An important contributor to this condition is the age-associated
      increase in endoplasmic reticulum (ER) stress. Here we show that the PKR-like ER
      kinase (PERK) integrates both cell-autonomous and non-autonomous ER stress
      stimuli to induce ISC proliferation. In addition to responding to cell-intrinsic
      ER stress, PERK is also specifically activated in ISCs by JAK/Stat signaling in
      response to ER stress in neighboring cells. The activation of PERK is required
      for homeostatic regeneration, as well as for acute regenerative responses, yet
      the chronic engagement of this response becomes deleterious in aging flies.
      Accordingly, knocking down PERK in ISCs is sufficient to promote intestinal
      homeostasis and extend lifespan. Our studies highlight the significance of the
      PERK branch of the unfolded protein response of the ER (UPRER) in intestinal
      homeostasis and provide a viable strategy to improve organismal health- and
      lifespan. 

PMID- 25945496
TI  - Improved neurological outcome by intramuscular injection of human amniotic fluid
      derived stem cells in a muscle denervation model.
AB  - PURPOSE: The skeletal muscle develops various degrees of atrophy and metabolic
      dysfunction following nerve injury. Neurotrophic factors are essential for muscle
      regeneration. Human amniotic fluid derived stem cells (AFS) have the potential to
      secrete various neurotrophic factors necessary for nerve regeneration. In the
      present study, we assess the outcome of neurological function by intramuscular
      injection of AFS in a muscle denervation and nerve anastomosis model. MATERIALS
      AND METHODS: Seventy two Sprague-Dawley rats weighing 200-250 gm were enrolled in
      this study. Muscle denervation model was conducted by transverse resection of a
      sciatic nerve with the proximal end sutured into the gluteal muscle. The nerve
      anastomosis model was performed by transverse resection of the sciatic nerve
      followed by four stitches reconnection. These animals were allocated to three
      groups: control, electrical muscle stimulation, and AFS groups. RESULTS: NT-3
      (Neurotrophin 3), BDNF (Brain derived neurotrophic factor), CNTF (Ciliary
      neurotrophic factor), and GDNF (Glia cell line derived neurotrophic factor) were
      highly expressed in AFS cells and supernatant of culture medium. Intra-muscular
      injection of AFS exerted significant expression of several neurotrophic factors
      over the distal end of nerve and denervated muscle. AFS caused high expression of
      Bcl-2 in denervated muscle with a reciprocal decrease of Bad and Bax. AFS
      preserved the muscle morphology with high expression of desmin and acetylcholine
      receptors. Up to two months, AFS produced significant improvement in
      electrophysiological study and neurological functions such as SFI (sciatic nerve
      function index) and Catwalk gait analysis. There was also significant
      preservation of the number of anterior horn cells and increased nerve myelination
      as well as muscle morphology. CONCLUSION: Intramuscular injection of AFS can
      protect muscle apoptosis and likely does so through the secretion of various
      neurotrophic factors. This protection furthermore improves the nerve regeneration
      in a long term nerve anastomosis model.

PMID- 25945497
TI  - An Integrated Assessment Model for Helping the United States Sea Scallop
      (Placopecten magellanicus) Fishery Plan Ahead for Ocean Acidification and
      Warming.
AB  - Ocean acidification, the progressive change in ocean chemistry caused by uptake
      of atmospheric CO2, is likely to affect some marine resources negatively,
      including shellfish. The Atlantic sea scallop (Placopecten magellanicus) supports
      one of the most economically important single-species commercial fisheries in the
      United States. Careful management appears to be the most powerful short-term
      factor affecting scallop populations, but in the coming decades scallops will be
      increasingly influenced by global environmental changes such as ocean warming and
      ocean acidification. In this paper, we describe an integrated assessment model
      (IAM) that numerically simulates oceanographic, population dynamic, and
      socioeconomic relationships for the U.S. commercial sea scallop fishery. Our
      primary goal is to enrich resource management deliberations by offering both
      short- and long-term insight into the system and generating detailed policy
      relevant information about the relative effects of ocean acidification,
      temperature rise, fishing pressure, and socioeconomic factors on the fishery
      using a simplified model system. Starting with relationships and data used now
      for sea scallop fishery management, the model adds socioeconomic decision making
      based on static economic theory and includes ocean biogeochemical change
      resulting from CO2 emissions. The model skillfully reproduces scallop population
      dynamics, market dynamics, and seawater carbonate chemistry since 2000. It
      indicates sea scallop harvests could decline substantially by 2050 under RCP 8.5
      CO2 emissions and current harvest rules, assuming that ocean acidification
      affects P. magellanicus by decreasing recruitment and slowing growth, and that
      ocean warming increases growth. Future work will explore different economic and
      management scenarios and test how potential impacts of ocean acidification on
      other scallop biological parameters may influence the social-ecological system.
      Future empirical work on the effect of ocean acidification on sea scallops is
      also needed. 

PMID- 25945498
TI  - Magnitude of cardiovascular risk factors in rural and urban areas in Benin:
      findings from a nationwide steps survey.
AB  - OBJECTIVE: To describe and compare the prevalences of CVRF in urban and rural
      populations of Benin. METHODS: Subjects were drawn from participants in the Benin
      Steps survey, a nationwide cross-sectional study conducted in 2008 using the
      World Health Organisation (WHO) stepwise approach to surveillance of chronic
      disease risk factors. Subjects aged above 24 and below 65 years were recruited
      using a five-stage random sampling process within households. Sociodemographic
      data, behavioral data along with medical history of high blood pressure and
      diabetes mellitus were collected in Step 1. Anthropometric parameters and blood
      pressure were measured in Step 2. Blood glucose and cholesterol levels were
      measured in Step 3. CVRF were defined according to WHO criteria. The prevalences
      of CVRF were assessed and the relationships between each CVRF and the area of
      residence (urban or rural), were evaluated using multivariable logistic
      regression models. RESULTS: Of the 6762 subjects included in the study, 2271 were
      from urban areas and 4491 were from rural areas. High blood pressure was more
      prevalent in urban than in rural areas, 29.9% (95% confidence intervals (95% CI):
      27.4, 32.5) and 27.5% (95% CI: 25.6, 29.5) respectively, p = 0.001 (p-value after
      adjustment for age and gender). Obesity was more prevalent in urban than in rural
      areas, 16.4% (95% CI: 14.4, 18.4) and 5.9% (95% CI: 5.1, 6.7), p<0.001. Diabetes
      was more prevalent in urban than in rural areas, 3.3% (95% CI: 2.1, 4.5) and 1.8%
      (95% CI: 1.2, 2.4), p = 0.004. Conversely, daily tobacco smoking was more
      prevalent in rural than in urban areas, 9.3% (95% CI: 8.1, 10.4) and 4.3% (95%
      CI: 3.1, 5.6), p<0.001. No differences in raised blood cholesterol were noted
      between the two groups. CONCLUSION: According to our data, CVRF are prevalent
      among adults in Benin, and variations between rural and urban populations are
      significant. It may be useful to take account of the heterogeneity in the
      prevalence of CVRF when planning and implementing preventive interventions.

PMID- 25945499
TI  - The role of structural dynamics of actin in class-specific myosin motility.
AB  - The structural dynamics of actin, including the tilting motion between the small
      and large domains, are essential for proper interactions with actin-binding
      proteins. Gly146 is situated at the hinge between the two domains, and we
      previously showed that a G146V mutation leads to severe motility defects in
      skeletal myosin but has no effect on motility of myosin V. The present study
      tested the hypothesis that G146V mutation impaired rotation between the two
      domains, leading to such functional defects. First, our study showed that
      depolymerization of G146V filaments was slower than that of wild-type filaments.
      This result is consistent with the distinction of structural states of G146V
      filaments from those of the wild type, considering the recent report that
      stabilization of actin filaments involves rotation of the two domains. Next, we
      measured intramolecular FRET efficiencies between two fluorophores in the two
      domains with or without skeletal muscle heavy meromyosin or the heavy meromyosin
      equivalent of myosin V in the presence of ATP. Single-molecule FRET measurements
      showed that the conformations of actin subunits of control and G146V actin
      filaments were different in the presence of skeletal muscle heavy meromyosin.
      This altered conformation of G146V subunits may lead to motility defects in
      myosin II. In contrast, distributions of FRET efficiencies of control and G146V
      subunits were similar in the presence of myosin V, consistent with the lack of
      motility defects in G146V actin with myosin V. The distribution of FRET
      efficiencies in the presence of myosin V was different from that in the presence
      of skeletal muscle heavy meromyosin, implying that the roles of actin
      conformation in myosin motility depend on the type of myosin. 

PMID- 25945500
TI  - Metformin versus Insulin in the Management of Pre-Gestational Diabetes Mellitus
      in Pregnancy and Gestational Diabetes Mellitus at the Korle Bu Teaching Hospital:
      A Randomized Clinical Trial.
AB  - OBJECTIVE: To determine if metformin monotherapy or metformin in combination with
      insulin is equally effective as insulin monotherapy at glycemic control in
      diabetes mellitus in pregnancy among Ghanaians. METHODS: This was a study
      involving 104 pregnant women with type 2 diabetes mellitus (T2DM) or gestational
      diabetes mellitus (GDM) at 20-30 weeks gestation. Participants were randomized
      into metformin and insulin treatment groups. Starting dose of metformin was 500
      mg once a day and increased gradually over two (2) weeks, to meet glycemic
      targets. Insulin was added if targets could not be reached on metformin alone at
      maximum doses. Total daily dose of premixed insulin at initiation was calculated
      as 0.3 IU/kg body weight and titrated upwards to achieve glycemic control.
      Glycemic profile monitoring was done every two weeks. RESULTS: The two hour post
      prandial blood glucose (2HPG) levels were significantly lower in the metformin
      group than the insulin group (p= 0.004). CONCLUSION: The findings of this study
      suggest that metformin monotherapy is effective in achieving glycemic targets in
      the management of diabetes in pregnancy. It is more effective than insulin in
      lowering the 2HPG level. TRIAL REGISTRATION: Australian New Zealand Clinical
      Trials Registry (ANZCTR) ACTRN12614000942651.

PMID- 25945501
TI  - Temperate snake community in South America: is diet determined by phylogeny or
      ecology?
AB  - Communities are complex and dynamic systems that change with time. The first
      attempts to explain how they were structured involve contemporary phenomena like
      ecological interactions between species (e.g., competition and predation) and led
      to the competition-predation hypothesis. Recently, the deep history hypothesis
      has emerged, which suggests that profound differences in the evolutionary history
      of organisms resulted in a number of ecological features that remain largely on
      species that are part of existing communities. Nevertheless, both phylogenetic
      structure and ecological interactions can act together to determine the structure
      of a community. Because diet is one of the main niche axes, in this study we
      evaluated, for the first time, the impact of ecological and phylogenetic factors
      on the diet of Neotropical snakes from the subtropical-temperate region of South
      America. Additionally, we studied their relationship with morphological and
      environmental aspects to understand the natural history and ecology of this
      community. A canonical phylogenetical ordination analysis showed that phylogeny
      explained most of the variation in diet, whereas ecological characters explained
      very little of this variation. Furthermore, some snakes that shared the habitat
      showed some degree of diet convergence, in accordance with the competition
      predation hypothesis, although phylogeny remained the major determinant in
      structuring this community. The clade with the greatest variability was the
      subfamily Dipsadinae, whose members had a very different type of diet, based on
      soft-bodied invertebrates. Our results are consistent with the deep history
      hypothesis, and we suggest that the community under study has a deep phylogenetic
      effect that explains most of the variation in the diet. 

PMID- 25945502
TI  - Adiponectin attenuates lung fibroblasts activation and pulmonary fibrosis induced
      by paraquat.
AB  - Pulmonary fibrosis is one of the most common complications of paraquat (PQ)
      poisoning, which demands for more effective therapies. Accumulating evidence
      suggests adiponectin (APN) may be a promising therapy against fibrotic diseases.
      In the current study, we determine whether the exogenous globular APN isoform
      protects against pulmonary fibrosis in PQ-treated mice and human lung
      fibroblasts, and dissect the responsible underlying mechanisms. BALB/C mice were
      divided into control group, PQ group, PQ + low-dose APN group, and PQ + high-dose
      APN group. Mice were sacrificed 3, 7, 14, and 21 days after PQ treatment. We
      compared pulmonary histopathological changes among different groups on the basis
      of fibrosis scores, TGF-beta1, CTGF and alpha-SMA pulmonary content via Western
      blot and real-time quantitative fluorescence-PCR (RT-PCR). Blood levels of MMP-9
      and TIMP-1 were determined by ELISA. Human lung fibroblasts WI-38 were divided
      into control group, PQ group, APN group, and APN receptor (AdipoR) 1 small
      interfering RNA (siRNA) group. Fibroblasts were collected 24, 48, and 72 hours
      after PQ exposure for assay. Cell viability and apoptosis were determined via Kit
      8 (CCK-8) and fluorescein Annexin V-FITC/PI double labeling. The protein and mRNA
      expression level of collagen type III, AdipoR1, and AdipoR2 were measured by
      Western blot and RT-PCR. APN treatment significantly decreased the lung fibrosis
      scores, protein and mRNA expression of pulmonary TGF-beta1, CTGF and alpha-SMA
      content, and blood MMP-9 and TIMP-1 in a dose-dependent manner (p<0.05).
      Pretreatment with APN significantly attenuated the reduced cell viability and up
      regulated collagen type III expression induced by PQ in lung fibroblasts,
      (p<0.05). APN pretreatment up-regulated AdipoR1, but not AdipoR2, expression in
      WI-38 fibroblasts. AdipoR1 siRNA abrogated APN-mediated protective effects in PQ
      exposed fibroblasts. Taken together, our data suggests APN protects against PQ
      induced pulmonary fibrosis in a dose-dependent manner, via suppression of lung
      fibroblast activation. Functional AdipoR1 are expressed by human WI-38 lung
      fibroblasts, suggesting potential future clinical applicability of APN against
      pulmonary fibrosis. 

PMID- 25945504
TI  - Correction: Nitrate Reduction to Nitrite, Nitric Oxide and Ammonia by Gut
      Bacteria under Physiological Conditions.

PMID- 25945503
TI  - Association between Number of Teeth and Chronic Systemic Diseases: A Cohort Study
      Followed for 13 Years.
AB  - BACKGROUND: There is growing evidence of an association between oral health,
      specifically dental status, and chronic systemic diseases. However, varying
      measures of dental status across different populations and low study sample has
      made comparison of studies and conclusion of findings unclear. Our aim is to
      examine whether the number of teeth as a measure of dental status is associated
      with incident chronic diseases in a cohort setting. METHODS: We conducted a
      cohort study among 24,313 middle-aged Germans followed up for 13 years. Data on
      number of teeth as a measure of dental status were obtained through self-reports.
      Outcomes were clinically-verified incident non-fatal myocardial infarction,
      stroke, type 2 diabetes mellitus, and cancer. Hazard ratio (HR) and 95%
      confidence intervals (CI) were obtained from Cox regression models. RESULTS:
      Increasing number of teeth is inversely related to risk of myocardial infarction
      (HR: 0.97; 95% CI: 0.96, 0.99). The full multivariate model of teeth groups
      showed a strong linear trend for myocardial infarction, a less strong trend for
      stroke, and no relation with type 2 diabetes mellitus and cancer in a competing
      risk model. Participants with 18-23 teeth and those without teeth were at 76%
      (95%CI: 1.04, 3) and 2.93 times (95%CI: 1.61, 5.18) higher risk of myocardial
      infarction compared to those with nearly all teeth (28-32 teeth). CONCLUSIONS:
      Number of teeth is specifically associated with myocardial infarction and not
      with other chronic disease indicating that dental status further strengthens the
      link between oral health and cardiovascular diseases.

PMID- 25945505
TI  - Insights into the gas phase oxidation of Ru(0001) on the mesoscopic scale using
      molecular oxygen.
AB  - We present an extensive mesoscale study of the initial gas phase oxidation of
      Ru(0001), employing in situ low-energy electron microscopy (LEEM), micro low
      energy electron diffraction (MU-LEED) and scanning tunneling microscopy (STM).
      The initial oxidation was investigated in a temperature range of 500-800 K at a
      constant oxygen pressure of p(O2) = 4 * 10(-5) mbar. Depending to the preparation
      temperature a dramatic change of the growth morphology of the RuO2 film was
      observed. At lower temperature (580 K) the RuO2(110) film grows anisotropically
      oriented along the high symmetry directions of the Ru(0001) substrate. At higher
      temperature (680 K), new rotational domains of RuO2(110) begin to appear, which
      are slightly rotated by up to 20 degrees  with respect to the high symmetry
      direction. These rotated RuO2(110) domains grow along slightly rotated step edges
      and reveal an isotropic growth morphology. Both the growth speed and the
      nucleation rate differ from that of the oxide growth at lower temperature (580
      K). 

PMID- 25945506
TI  - Processing of Neutrophil alpha-Defensins Does Not Rely on Serine Proteases In
      Vivo.
AB  - The alpha-defensins, human neutrophil peptides (HNPs) are the predominant
      antimicrobial peptides of neutrophil granules. They are synthesized in
      promyelocytes and myelocytes as proHNPs, but only processed in promyelocytes and
      stored as mature HNPs in azurophil granules. Despite decades of search, the
      mechanisms underlying the posttranslational processing of neutrophil defensins
      remain unidentified. Thus, neither the enzyme that processes proHNPs nor the
      localization of processing has been identified. It has been hypothesized that
      proHNPs are processed by the serine proteases highly expressed in promyelocytes:
      Neutrophil elastase (NE), cathepsin G (CG), and proteinase 3 (PR3), all of which
      are able to process recombinant proHNP into HNP in vitro. We investigated whether
      serine proteases are in fact responsible for processing of proHNP in human bone
      marrow cells and in human and murine myeloid cell lines. Subcellular
      fractionation of the human promyelocytic cell line PLB-985 demonstrated proHNP
      processing to commence in fractions containing endoplasmic reticulum. Processing
      of 35S-proHNP was insensitive to serine protease inhibitors. Simultaneous
      knockdown of NE, CG, and PR3 did not decrease proHNP processing in primary human
      bone marrow cells. Furthermore, introduction of NE, CG, and PR3 into murine
      promyelocytic cells did not enhance the proHNP processing capability. Finally,
      two patients suffering from Papillon-Lefevre syndrome, who lack active neutrophil
      serine proteases, demonstrated normal levels of fully processed HNP in peripheral
      neutrophils. Contradicting earlier assumptions, our study found serine proteases
      dispensable for processing of proHNPs in vivo. This calls for study of other
      protease classes in the search for the proHNP processing protease(s). 

PMID- 25945508
TI  - Towards Development of Clustering Applications for Large-Scale Comparative
      Genotyping and Kinship Analysis Using Y-Short Tandem Repeats.
AB  - Y-chromosome short tandem repeats (Y-STRs) are genetic markers with practical
      applications in human identification. However, where mass identification is
      required (e.g., in the aftermath of disasters with significant fatalities), the
      efficiency of the process could be improved with new statistical approaches.
      Clustering applications are relatively new tools for large-scale comparative
      genotyping, and the k-Approximate Modal Haplotype (k-AMH), an efficient algorithm
      for clustering large-scale Y-STR data, represents a promising method for
      developing these tools. In this study we improved the k-AMH and produced three
      new algorithms: the Nk-AMH I (including a new initial cluster center selection),
      the Nk-AMH II (including a new dominant weighting value), and the Nk-AMH III
      (combining I and II). The Nk-AMH III was the superior algorithm, with mean
      clustering accuracy that increased in four out of six datasets and remained at
      100% in the other two. Additionally, the Nk-AMH III achieved a 2% higher overall
      mean clustering accuracy score than the k-AMH, as well as optimal accuracy for
      all datasets (0.84-1.00). With inclusion of the two new methods, the Nk-AMH III
      produced an optimal solution for clustering Y-STR data; thus, the algorithm has
      potential for further development towards fully automatic clustering of any large
      scale genotypic data. 

PMID- 25945509
TI  - Defect-free Naphthalene Diimide Bithiophene Copolymers with Controlled Molar Mass
      and High Performance via Direct Arylation Polycondensation.
AB  - A highly efficient, simple, and environmentally friendly protocol for the
      synthesis of an alternating naphthalene diimide bithiophene copolymer (PNDIT2)
      via direct arylation polycondensation (DAP) is presented. High molecular weight
      (MW) PNDIT2 can be obtained in quantitative yield using aromatic solvents. Most
      critical is the suppression of two major termination reactions of NDIBr end
      groups: nucleophilic substitution and solvent end-capping by aromatic solvents
      via C-H activation. In situ solvent end-capping can be used to control MW by
      varying monomer concentration, whereby end-capping is efficient and MW is low for
      low concentration and vice versa. Reducing C-H reactivity of the solvent at
      optimized conditions further increases MW. Chain perfection of PNDIT2 is
      demonstrated in detail by NMR spectroscopy, which reveals PNDIT2 chains to be
      fully linear and alternating. This is further confirmed by investigating the
      optical and thermal properties as a function of MW, which saturate at Mn ~ 20
      kDa, in agreement with controls made by Stille coupling. Field-effect transistor
      (FET) electron mobilities MUsat up to 3 cm(2)/(V.s) are measured using off-center
      spin-coating, with FET devices made from DAP PNDIT2 exhibiting better
      reproducibility compared to Stille controls. 

PMID- 25945507
TI  - Women and Lung Disease. Sex Differences and Global Health Disparities.
AB  - There is growing evidence that a number of pulmonary diseases affect women
      differently and with a greater degree of severity than men. The causes for such
      sex disparity is the focus of this Blue Conference Perspective review, which
      explores basic cellular and molecular mechanisms, life stages, and clinical
      outcomes based on environmental, sociocultural, occupational, and infectious
      scenarios, as well as medical health beliefs. Owing to the breadth of issues
      related to women and lung disease, we present examples of both basic and clinical
      concepts that may be the cause for pulmonary disease disparity in women. These
      examples include those diseases that predominantly affect women, as well as the
      rising incidence among women for diseases traditionally occurring in men, such as
      chronic obstructive pulmonary disease. Sociocultural implications of pulmonary
      disease attributable to biomass burning and infectious diseases among women in
      low- to middle-income countries are reviewed, as are disparities in respiratory
      health among sexual minority women in high-income countries. The implications of
      the use of complementary and alternative medicine by women to influence
      respiratory disease are examined, and future directions for research on women and
      respiratory health are provided. 

PMID- 25945510
TI  - Efficient photoinduced charge accumulation in reduced graphene oxide coupled with
      titania nanosheets to show highly enhanced and persistent conductance.
AB  - Tuning of the electrical properties of graphene via photoexcitation of a
      heteroassembled material has started to attract attention for electronic and
      optoelectronic applications. Actually photoinduced carrier doping from the
      hexagonal boron nitride (h-BN) substrate greatly modulated the transport property
      of the top layer graphene, showing promising potential for this approach.
      However, for practical applications, the large scale production of this two
      dimensional heterostructure is needed. Here, a superlattice film constructed from
      reduced graphene oxide (rGO) and photoactive titania nanosheets (Ti0.87O2(0.52-))
      was employed as a channel to construct a field effect transistor (FET) device,
      and its UV light response on the electrical transport property was examined. The
      UV light illumination induced significant improvement of the electrical
      conductance by ~7 times on the basis of simultaneous enhancements of the electron
      carrier concentration and its mobility in rGO. Furthermore, the polarity of the
      FET response changed from ambipolar to n-type unipolar. Such modulated properties
      persisted in vacuum even after the UV light was turned off. These interesting
      behaviors may be explained in terms of photomodulation effects from Ti0.87O2(0.52
      ) nanosheets. The photoexcited electrons in Ti0.87O2(0.52-) are injected into rGO
      to increase the electron carrier concentration as high as 7.6*10(13) cm(-2). On
      the other hand, the holes are likely trapped in the Ti0.87O2(0.52-) nanosheets.
      These photocarriers undergo reduction and oxidation of oxygen and water molecules
      adsorbed in the film, respectively, which act as carrier scattering centers,
      contributing to the enhancement of the carrier mobility. Since the film likely
      contains more water molecules than oxygen, upon extinction of UV light, a major
      portion of electrons (~80% of the concentration at the UV off) survives in rGO,
      showing the highly enhanced conductance for days. This surpassing photomodulated
      FET response and its persistency observed in the present superlattice system of
      rGO/Ti0.87O2(0.52-) are noteworthy compared with previous studies such as the
      device with a heteroassembly of graphene/h-BN.

PMID- 25945511
TI  - Detection of carotid artery calcification on the panoramic images of post
      menopausal females is significantly associated with severe abdominal aortic
      calcification: a risk indicator of future adverse vascular events.
AB  - OBJECTIVES: Outcome studies among post-menopausal females with calcified carotid
      artery plaque (CCAP) on their panoramic images have not been previously
      undertaken. We sought to compare the extent of abdominal aortic calcification
      (AAC) on lateral lumbar spine radiographs (LLSRs), among groups of females with
      (CCAP+) and without (CCAP-) carotid lesions on their panoramic images. "Severe"
      levels of AAC have previously been validated as a risk indicator of future
      adverse cardiovascular events. METHODS: This cross-sectional case-control study
      included a "CCAP+ group" consisting of females more than 50 years of age having
      the carotid lesion diagnosed by their dentists and an atherogenic risk factor
      (age, body mass index, hypertension, diabetes and dyslipidaemia)-matched "CCAP-
      group". A physician radiologist, using the Framingham index, evaluated the LLSRs
      for the magnitude of AAC. Summary statistics for key variables were computed and
      conditional logistic regression techniques were considered. RESULTS: Members of
      the CCAP+ group were significantly (p=0.038) more likely to demonstrate "severe"
      levels of AAC on their LLSRs than members of the CCAP group. CONCLUSIONS: This is
      the first published study demonstrating that CCAP on panoramic images of post
      menopausal females is significantly associated with "severe" levels of AACs on
      LLSRs independent of traditional risk factors. Given that these levels of AAC are
      a validated risk indicator of future myocardial infarction and stroke, dentists
      must evaluate the panoramic images of post-menopausal females for the presence of
      CCAP. Patients with carotid atheromas should be referred to their physicians for
      further evaluation given the systemic implications.

PMID- 25945512
TI  - Clinical, pathological and unusual MRI features of five synovial sarcomas in head
      and neck.
AB  - OBJECTIVE: Synovial sarcoma (SS) of the head and neck is an unusual malignancy.
      This article documents five SSs in this region. METHODS: All the patients
      underwent MR examinations. Four lesions received surgical ablation; one was
      treated with radiotherapy before surgery. The clinical, pathological and MRI
      features were reviewed. RESULTS: Four of all five cases were monophasic fibrous
      type SS, and the other one was biphasic type that was the fourth documented SS
      located in the nasopharynx. The symptoms were varied. All the masses were well
      defined, mainly homogeneous and solid; three of them arose adjacent to the minor
      joint. The mass parenchyma showed isointense signal on T1 weighted imaging
      similar to that of the skeletal muscle and hyperintense signal on T2 weighted
      imaging with remarkable enhancement. Two cases were found with fibrous septum,
      one with haemorrhage and one with cystic degeneration. Epithelial membrane
      antigens (EMAs) were all positive. The positive rate of cytokeratin (CK), part
      pan-CK antibody (AE1/3) and vimentin (Vim) were 50%, 75%, 75%, respectively.
      CONCLUSION: Well-defined head and neck masses frequently arise adjacent to the
      minor joint, which are mainly homogeneous and solid, with isointense signal on T1
      weighted MRI and hyperintense signal on T2 weighted MRI, and remarkable
      enhancement should evoke the diagnosis of SS. The positive staining of
      Vim?AE1/3?EMA and CK facilitates the final diagnosis. ADVANCES IN KNOWLEDGE: The
      article documents the fourth SS involving the nasopharynx; other locations were
      also uncommon; three of them arose adjacent to the minor joint. The clinical,
      pathology and uncommon MR features of SS in the head and neck are also
      documented.

PMID- 25945513
TI  - Molecular mechanism of action of chlorogenic acid on erythrocyte and lipid
      membranes.
AB  - The high antioxidant capacity of chlorogenic acid (CGA) in respect to biological
      systems is commonly known, though the molecular mechanism underlying that
      activity is not known. The aim of the study was to determine that mechanism at
      the molecular and cell level, in particular with regard to the erythrocyte and
      the lipid phase of its membrane. The effect of CGA on erythrocytes and lipid
      membranes was studied using microscopic, spectrophotometric and electric methods.
      The biological activity of the acid was determined on the basis of changes in the
      physical parameters of the membrane, in particular its osmotic resistance and
      shapes of erythrocytes, polar head packing order and fluidity of erythrocyte
      membrane as well as capacity and resistivity of black lipid membrane (BLM). The
      study showed that CGA becomes localized mainly in the outer part of membrane,
      does not induce hemolysis or change the osmotic resistance of erythrocytes, and
      induces formation of echinocytes. The values of generalized polarization and
      fluorescence anisotropy indicate that CGA alters the hydrophilic region of the
      membrane, practically without changing the fluidity in the hydrophobic region.
      The assay of electric parameters showed that CGA causes decreased capacity and
      resistivity of black lipid membranes. The overall result is that CGA takes
      position mainly in the hydrophilic region of the membrane, modifying its
      properties. Such localization allows the acid to reduce free radicals in the
      immediate vicinity of the cell and hinders their diffusion into the membrane
      interior. 

PMID- 25945514
TI  - Iodine-catalyzed radical oxidative annulation for the construction of
      dihydrofurans and indolizines.
AB  - Through iodine catalysis, the direct oxidative coupling/annulation of beta-keto
      esters or 2-pyridinyl-beta-esters with alkenes was achieved. This reaction
      procedure provides a simple and selective way for the synthesis of dihydrofurans
      and indolizines in one step. 

PMID- 25945515
TI  - Pharmaceuticals and personal care products: A critical review of the impacts on
      fish reproduction.
AB  - Research in environmental toxicology involving pharmaceuticals and personal care
      products (PPCPs) has increased greatly over the last 10-15 years. Much research
      has been focused on the endocrine-disrupting potential of PPCPs, as they relate
      to negative population impacts of aquatic organisms. This review assesses the
      current data on the reported effects of PPCPs on fish reproduction with an
      emphasis on fecundity, a predictor of population effects. Studies of both
      individual PPCPs and PPCP mixtures are presented. As the majority of individual
      PPCP studies reviewed demonstrate negative effects on fish fecundity, we relate
      these findings to detected surface water concentrations of these compounds. Very
      few studies involving PPCP mixtures have been conducted; however, the need for
      these types of studies is warranted as fish are most likely exposed to mixtures
      of PPCPs in the wild. In addition, laboratory and field assessments of wastewater
      treatment plant (WWTP) effluents, a major source of PPCPs, are reviewed. Much of
      the data provided from these assessments are variable and do not generally
      demonstrate negative impacts on reproduction, or the studies are unable to
      directly associate observed effects with WWTP effluents. Finally, future research
      considerations are outlined to provide an avenue into understanding how wild
      populations of fish are affected by PPCPs. These considerations are aimed at
      determining the adaptation potential of fish exposed to mixtures of PPCPs over
      multiple generations. As global use of PPCPs continually rises, the need to
      discern the effects of chronic exposure to PPCPs is greatly increased. 

PMID- 25945517
TI  - Three-Dimensional Porous HxTiS2 Nanosheet-Polyaniline Nanocomposite Electrodes
      for Directly Detecting Trace Cu(II) Ions.
AB  - In the present work, three-dimensional porous HxTiS2 nanosheet-polyaniline (PANI)
      nanocomposites were first synthesized by a two-step method. First, HxTiS2
      ultrathin nanosheets were prepared by the lithium intercalation and exfoliation
      method, followed by the surface polymerization reactions of aniline. The
      influences of the amount of HxTiS2 nanosheets on the nanocomposite morphology and
      electrochemical performances of the nanocomposites modified glass carbon
      electrode (HxTiS2 nanosheet-PANI/GCE) were investigated. The results demonstrated
      that the incorporation of HxTiS2 nanosheets as a suitable substrate can regulate
      the growth of PANI, enhance the electrode stability and improve interfacial
      electron transfer rates. In addition, based on the nanocomposites, we developed a
      novel electrochemical sensor to directly detect trace Cu(2+), and discovered that
      the coordination interaction between Cu(2+) cations and the N atoms of the imine
      moieties in PANI endowed the electrochemical sensor with high selectivity.
      Because of the synergetic effects of HxTiS2 nanosheets and PANI, the as-prepared
      electrochemical sensor exhibited highly sensitive and selective assaying of
      Cu(2+) with a detection limit of 0.7 nM (signal-to-noise ratio (S/N) equal to 3)
      and a linear range from 25 nM to 5 MUM, under optimal conditions. 

PMID- 25945516
TI  - Mechanistic significance of the si-o-pd bond in the palladium-catalyzed cross
      coupling reactions of arylsilanolates.
AB  - Through the combination of reaction kinetics (both stoichiometric and catalytic),
      solution- and solid-state characterization of arylpalladium(II) arylsilanolates,
      and computational analysis, the intermediacy of covalent adducts containing Si-O
      Pd linkages in the cross-coupling reactions of arylsilanolates has been
      unambiguously established. Two mechanistically distinct pathways have been
      demonstrated: (1) transmetalation via a neutral 8-Si-4 intermediate that
      dominates in the absence of free silanolate (i.e., stoichiometric reactions of
      arylpalladium(II) arylsilanolate complexes), and (2) transmetalation via an
      anionic 10-Si-5 intermediate that dominates in the cross-coupling under catalytic
      conditions (i.e., in the presence of free silanolate). Arylpalladium(II)
      arylsilanolate complexes bearing various phosphine ligands have been isolated,
      fully characterized, and evaluated for their kinetic competence under thermal
      (stoichiometric) and anionic (catalytic) conditions. Comparison of the rates for
      thermal and anionic activation suggested, but did not prove, that intermediates
      containing the Si-O-Pd linkage were involved in the cross-coupling process. The
      isolation of a coordinatively unsaturated, T-shaped arylpalladium(II)
      arylsilanolate complex ligated with t-Bu3P allowed the unambiguous demonstration
      of the operation of both pathways involving 8-Si-4 and 10-Si-5 intermediates.
      Three kinetic regimes were identified: (1) with 0.5-1.0 equiv of added silanolate
      (with respect to arylpalladium bromide), thermal transmetalation via a neutral 8
      Si-4 intermediate; (2) with 1.0-5.0 equiv of added silanolate, activated
      transmetalation via an anionic 10-Si-5 intermediate; and (3) with >5.0 equiv of
      added silanolate, concentration-independent (saturation) activated
      transmetalation via an anionic 10-Si-5 intermediate. Transition states for the
      intramolecular transmetalation of neutral (8-Si-4) and anionic (10-Si-5)
      intermediates have been located computationally, and the anionic pathway is
      favored by 1.8 kcal/mol. The energies of all intermediates and transition states
      are highly dependent on the configuration around the palladium atom. 

PMID- 25945518
TI  - Comparison in Joint-Position Sense and Muscle Coactivation Between Anterior
      Cruciate Ligament-Deficient and Healthy Individuals.
AB  - CONTEXT: Tearing of the anterior cruciate ligament (ACL) may disrupt the ability
      to recognize the knee position in space during limb-repositioning tasks, which is
      referred to as joint-position sense (JPS). Impairments in JPS have been shown to
      be lower during active than passive repositioning tasks, thus suggesting that
      coactivation patterns of the muscles surrounding the knee might compensate for
      the disrupted JPS and ensure accurate limb repositioning in ACL-deficient
      individuals. OBJECTIVE: To investigate muscle coactivation patterns during JPS
      repositioning tasks in ACL-deficient and healthy individuals. DESIGN: Prospective
      observational study. SETTING: Functional assessment laboratory. PARTICIPANTS: 8
      men age 25 +/- 8 y with isolated ACL rupture and 10 men age 30 +/- 4 y with no
      history of knee injury. INTERVENTION: JPS was evaluated by means of an
      electrogoniometer in a sitting position during either passive or active joint
      positioning and -repositioning tasks with a 40 degrees  target knee angle. MAIN
      OUTCOME MEASURES: Root mean square (RMS) of the surface electromyogram from the
      vastus lateralis and biceps femoris muscles was measured during active joint
      positioning and repositioning. RESULTS: Healthy participants showed a significant
      decrease in vastus lateralis RMS (-19%) and an increase in biceps femoris RMS
      (+26%) during joint repositioning compared with positioning. In contrast, ACL
      deficient patients showed no modulation in muscle coactivation between joint
      positioning and repositioning, although they exhibited significantly lower RMS of
      the vastus lateralis (injured limb, -28%; uninjured limb, -21%) and higher RMS of
      the biceps femoris (injured limb, +19%; uninjured limb, +30%) than the healthy
      participants during joint positioning. CONCLUSIONS: The lack of modulation in
      muscle coactivation patterns between joint positioning and repositioning in ACL
      deficient patients might be attributed to disrupted neural control after the
      injury-related loss of proprioceptive information. These results should be taken
      into account in the design of rehabilitation protocols with emphasis on muscle
      coactivation and JPS.

PMID- 25945519
TI  - Advances in Research on Caenorhabditis elegans: Application to Plant Parasitic
      Nematodes.

PMID- 25945520
TI  - Dynamics of Metal Partitioning at the Cell-Solution Interface: Implications for
      Toxicity Assessment under Growth-Inhibiting Conditions.
AB  - Metal toxicity toward microorganisms is usually evaluated by determining growth
      inhibition. To achieve a mechanistic interpretation of such toxic effects, the
      intricate coupling between cell growth kinetics and metal partitioning dynamics
      at the cell-solution interface over time must be considered on a quantitative
      level. A formalism is elaborated to evaluate cell-surface-bound, internalized,
      and extracellular metal fractions in the limit where metal uptake kinetics is
      controlled by internalization under noncomplexing medium conditions. Cell growth
      kinetics is tackled using the continuous logistic equation modified to include
      growth inhibition by metal accumulation to intracellular or cell surface sites.
      The theory further includes metal-proton competition for adsorption at cell
      surface binding sites, as well as possible variation of cell size during exposure
      to metal ions. The formalism elucidates the dramatic impacts of initial cell
      concentration on metal bioavailability and toxicity over time, in agreement with
      reported algae bioassays. It further highlights that appropriate definition of
      toxicity endpoints requires careful inspection of the ratio between exposure time
      scale and time scale of metal depletion from bulk solution. The latter depends on
      metal internalization-excretion rate constants, microorganism growth, and the
      extent of metal adsorption on nonspecific, transporter, and growth inhibitory
      sites. As an application of the theory, Cd toxicity in the algae
      Pseudokirchneriella subcapitata is interpreted from constrained modeling of cell
      growth kinetics and of interfacial Cd-partitioning dynamics measured under
      various exposure conditions. 

PMID- 25945521
TI  - Morphology, mechanical stability, and protective properties of ultrathin gallium
      oxide coatings.
AB  - Ultrathin gallium oxide layers with a thickness of 2.8 +/- 0.2 nm were
      transferred from the surface of liquid gallium onto solid substrates, including
      conjugated polymer poly(3-hexylthiophene) (P3HT). The gallium oxide exhibits high
      mechanical stability, withstanding normal pressures of up to 1 GPa in contact
      mode scanning force microscopy imaging. Moreover, it lowers the rate of
      photodegradation of P3HT by 4 orders of magnitude, as compared to uncovered P3HT.
      This allows us to estimate the upper limits for oxygen and water vapor
      transmission rates of 0.08 cm(3) m(-2) day(-1) and 0.06 mg m(-2) day(-1),
      respectively. Hence, similar to other highly functional coatings such as
      graphene, ultrathin gallium oxide layers can be regarded as promising candidates
      for protective layers in flexible organic (opto-)electronics and photovoltaics
      because they offer permeation barrier functionalities in conjunction with high
      optical transparency. 

PMID- 25945523
TI  - ATG14 controls SNARE-mediated autophagosome fusion with a lysosome.
AB  - Autophagosome fusion with a lysosome constitutes the last barrier for autophagic
      degradation. It is speculated that this fusion process is precisely and tightly
      regulated. Recent genetic evidence suggests that a set of SNARE proteins,
      including STX17, SNAP29, and VAMP8, are essential for the fusion between
      autophagosomes and lysosomes. However, it remains unclear whether these SNAREs
      are fusion competent and how their fusogenic activity is specifically regulated
      during autophagy. Using a combination of biochemical, cell biology, and genetic
      approaches, we demonstrated that fusogenic activity of the autophagic SNARE
      complex is temporally and spatially controlled by ATG14/Barkor/Atg14L, an
      essential autophagy-specific regulator of the class III phosphatidylinositol 3
      kinase complex (PtdIns3K). ATG14 directly binds to the STX17-SNAP29 binary
      complex on autophagosomes and promotes STX17-SNAP29-VAMP8-mediated autophagosome
      fusion with lysosomes. ATG14 homo-oligomerization is required for SNARE binding
      and fusion promotion, but is dispensable for PtdIns3K stimulation and
      autophagosome biogenesis. Consequently, ATG14 homo-oligomerization is required
      for autophagosome fusion with a lysosome, but is dispensable for autophagosome
      biogenesis. These data support a key role of ATG14 in controlling autophagosome
      fusion with a lysosome. 

PMID- 25945522
TI  - BRCA2 is needed for both repair and cell cycle arrest in mammalian cells exposed
      to S23906, an anticancer monofunctional DNA binder.
AB  - Repair of DNA-targeted anticancer agents is an active area of investigation of
      both fundamental and clinical interest. However, most studies have focused on a
      small number of compounds limiting our understanding of both DNA repair and the
      DNA damage response. S23906 is an acronycine derivative that shows strong
      activity toward solid tumors in experimental models. S23906 forms bulky
      monofunctional DNA adducts in the minor groove which leads to destabilization of
      the double-stranded helix. We now report that S23906 induces formation of DNA
      double strand breaks that are processed through homologous recombination (HR) but
      not Non-Homologous End-Joining (NHEJ) repair. Interestingly, S23906 exposure was
      accompanied by a higher sensitivity of BRCA2-deficient cells compared to other HR
      deficient cell lines and by an S-phase accumulation in wild-type (wt), but not in
      BRCA2-deficient cells. Recently, we have shown that S23906-induced S phase arrest
      was mediated by the checkpoint kinase Chk1. However, its activated phosphorylated
      form is equally induced by S23906 in wt and BRCA2-deficient cells, likely
      indicating a role for BRCA2 downstream of Chk1. Accordingly, override of the S
      phase arrest by either 7-hydroxystaurosporine (UCN-01) or AZD7762 potentiates the
      cytotoxic activity of S23906 in wt, but not in BRCA2-deficient cells. Together,
      our findings suggest that the pronounced sensitivity of BRCA2-deficient cells to
      S23906 is due to both a defective S-phase arrest and the absence of HR repair.
      Tumors with deficiencies for proteins involved in HR, and BRCA2 in particular,
      may thus show increased sensitivity to S23906, thereby providing a rationale for
      patient selection in clinical trials.

PMID- 25945524
TI  - Ketorolac eye drops reduce inflammation and delay re-epithelization in response
      to corneal alkali burn in rabbits, without affecting iNOS or MMP-9.
AB  - PURPOSES: To assess the effects of 0.5% ketorolac tromethamine without
      preservatives on the expression of iNOS and MMP-9 in alkali burn ulcers. METHODS:
      Twelve eyes of 120-day-old male rabbits were treated (TG) every 6 h with 0.5%
      ketorolac tromethamine and 12 other eyes were treated with saline solution (CG),
      immediately after the occurrence of ulcers by 1 M sodium hydroxide (NaOH). Re
      epithelialization was monitored using fluorescein every 6 h. After 24 h, six
      corneas (n=6) of each group were collected (M1). The others (n=6) were collected
      after reepithelialization (M2). At both moments, the inflammatory infiltrate and
      the conditions of the newly formed epithelium were histologically analyzed. iNOS
      and MMP-9 were evaluated by immunohistochemistry. RESULTS: Mean epithelialization
      time in TG was 55 +/- 0.84 h. In CG, it was 44 +/- 1.06 h (p=0.001). At M1,
      corneas of TG had lower inflammatory exudation compared with (p <0.001). At M2,
      TG revealed discrete inflammatory exudation (p>0.05) and lower numbers of
      epithelial layers compared with CG. The mean iNOS in stromal cells did not differ
      in TG over both moments compared with CG (p>0.05) At M2, the central corneal
      region expressed more iNOS in both groups compared with the peripheral region. No
      significant differences were observed in iNOS scores of epithelial immunostaining
      between the groups and across M1 and M2 (p=0.69). Epithelial immunostaining
      scores for MMP-9 did not differ in TG compared with CG (p=0.69). The average
      immunostaining score of MMP-9 in stromal cells showed no differences between
      groups or moments. There was no correlation between immunostaining of iNOS and
      MMP-9 or between the amount of inflammatory cells and immunostaining of iNOS.
      CONCLUSIONS: Use of 0.5% keratolac tromethamine reduced inflammation and delayed
      reepithelialization in a cornea alkali burn model without impacting the
      expression of iNOS or MMP-9.

PMID- 25945525
TI  - Results of pars plana vitrectomy after complicated phacoemulsification surgery.
AB  - PURPOSE: To identify the causes and outcomes of pars plana vitrectomy (PPV) in
      patients undergoing phacoemulsification with intraoperative complication and to
      analyze whether the interval between phacoemulsification and PPV interferes with
      best-corrected final visual acuity. METHODS: This descriptive and retrospective
      analytical study was conducted in Parana Eye Hospital in 2013. Data were
      collected from medical records of 38 patients who underwent complicated
      phacoemulsification and also required PPV. RESULTS: The most frequent
      complication as a result of phacoemulsification was posterior capsule rupture,
      observed in 35 patients (92.10%), followed by capsular bag detachment, in three
      patients (7.89%). Twenty-eight patients (73.68%) had cortical fragments that were
      removed during PPV. Twelve patients (31.57%) had their intraocular lens
      repositioned. PPV was performed on the same day of phacoemulsification in one
      patient (2.63%), within 1 week in 15 patients (39.47%), between 1 week and 1
      month in 13 patients (34.21%), and 1 month after phacoemulsification in 9
      patients (23.68%). CONCLUSION: This study is in agreement with worldwide
      literature, asserting that major complications of phacoemulsification are
      posterior capsule rupture and capsular bag detachment, and in addition, there is
      an improvement in the final visual acuity in almost half the cases, even when
      there are complications during modern cataract surgery, when complementary
      appropriate treatment is provided.

PMID- 25945526
TI  - Femtosecond-assisted intrastromal corneal ring implantation for keratoconus
      treatment: a comparison with crosslinking combination.
AB  - PURPOSE: To compare visual outcomes, corneal astigmatism, and keratometric
      readings in patients with keratoconus who underwent intrastromal corneal ring
      implantation (ICRSI) alone with those who underwent ICRSI combined with
      ultraviolet A riboflavin-mediated corneal collagen crosslinking (CXL). METHODS:
      Pre- and post-operative best-corrected distance visual acuity (BCDVA), spherical
      error, cylindrical error, and mean keratometry were retrospectively compared over
      a period of 2 years in patients with keratoconus who underwent only ICRSI (group
      1) versus those in patients who underwent combined ICRSI-CXL (group 2). RESULTS:
      Thirty-two eyes of 31 patients were evaluated. CXL was performed in 10 cases
      (31%), and there were no complications or need for ring repositioning. BCDVA
      improved from 0.54 to 0.18 in the group 1 and from 0.56 to 0.17 in the group 2.
      Spherical and cylindrical errors and mean keratometry values significantly
      decreased in both groups. No patient postoperatively had visual acuity (VA) of
      less than 20/60 on refraction, and 78% exhibited VA better than or equal to 20/40
      with spectacles (72% of group 1 and 90% of group 2). Improvement in the spherical
      equivalent (SE) value was observed in the group 1 (from -5.89 +/- 3.37
      preoperatively to -2.65 +/- 2.65 postoperatively; p<0.05) and group 2 (from -6.91
      +/- 1.93 preoperatively to -2.11 +/- 3.01 postoperatively; p<0.05). CONCLUSION:
      Both techniques can be considered safe and effective in improving VA and
      refractive SE values, in decreasing the curvature of the cone apex in the
      topographical analysis, and in decreasing corrected diopters postoperatively in
      patients with keratoconus.

PMID- 25945527
TI  - Blood gas analyzer utility in evaluating oxygen kinetics of the aqueous humor.
AB  - PURPOSE: To measure the partial pressure of oxygen (PO2) and carbon dioxide
      (PCO2) and the pH of aqueous humor (AH) and arterial blood samples from rabbits
      using a blood gas analyzer. METHODS: Twenty New Zealand rabbits were anesthetized
      intramuscularly with ketamine and xylazine and were then allowed to breathe room
      air. Using a gas blood analyzer, arterial blood and AH samples were analyzed for
      PO2, PCO2, and pH. RESULTS: The mean arterial blood pressure was 87.14 +/- 15.0
      mmHg. The mean blood and AH PO2 were 95.18 +/- 11.76 mmHg and 88.83 +/- 9.92
      mmHg, the mean blood and AH PCO2 were 25.86 +/- 5.46 mmHg and 29.50 +/- 5.36
      mmHg, and the mean blood and AH pH were 7.38 +/- 0.06 and 7.33 +/- 0.09,
      respectively. CONCLUSION:  CONCLUSIONS: The blood gas analyzer was easily
      employed to evaluate the aqueous humor in rabbits. When comparing the results of
      studies evaluating aqueous PO2, care should be taken to determine the methods
      used in these studies.

PMID- 25945528
TI  - Association of high-density lipoprotein and apolipoprotein E genetic variants
      with age-related macular degeneration.
AB  - PURPOSE: This study aimed to evaluate the association of age-related macular
      degeneration (AMD) with apolipoprotein E (APOE) variants and serum lipid
      profiles, including levels and fractions of total serum cholesterol (TC), low
      density lipoprotein cholesterol (LDLc), and high-density lipoprotein cholesterol
      (HDLc), and triglycerides (TG). METHODS: Genotyping of APOE-HhaI was performed in
      134 patients (study group, SG) and 164 individuals without AMD (control group,
      CG), aged 50-89 years. Lipid profiles were analyzed in a subgroup of 30 subjects
      of both groups, matched according to age and sex. The significance level was set
      at P<0.05. RESULTS: APOE E3/E3 was more prevalent (SG=74.6%; CG=77.4%), with no
      difference between both groups (P=0.667). The same result was observed for risk
      genotypes (APOE E -/2: SG=7.4%; CG=10.3%, P=0.624). Serum levels of TC, LDLc, and
      TG revealed similar median values between SG (193.5, 116, and 155 mg/dL,
      respectively) and CG (207.5, 120, and 123.5 mg/dL, respectively; P >0.05). For
      HDLc, a higher median value was observed in SG (53.3 mg/dL) versus CG (42.5
      mg/dL; P=0.016). Logistic regression analysis showed the same value, and the
      HDLc/TC ratio was -11.423 (P=0.014), as also confirmed by an increase in HDLc in
      SG. The association between lipid profiles and apolipoprotein E genotypes was
      similar in both groups (P>0.05). CONCLUSION: APOE-HhaI is not associated with
      AMD. However, an increase in serum HDLc level appears to exert a protective
      effect against the disease, irrespective of the genetic variants of apoE.

PMID- 25945529
TI  - Cytotoxicity and genotoxicity of intravitreal adalimumab administration in rabbit
      retinal cells.
AB  - PURPOSE: To assess the cytotoxicity and genotoxicity of intravitreal adalimumab
      treatment in an animal experimental model using cytological and molecular
      techniques. METHODS: Eighteen rabbits were randomly assigned to three groups:
      control, adalimumab treatment, and placebo. Cytotoxicity on retinal cells was
      evaluated using flow cytometry assays to determine the level of apoptosis and
      necrosis. Genotoxicity was evaluated by comet assays to assess DNA damage, and
      quantitative real-time polymerase chain reaction (qPCR) was used to evaluate
      expression of apoptosis-inducing caspases (8 and 3). RESULTS: No cytotoxicity or
      genotoxicity was observed in any of the two treatment groups (adalimumab and
      placebo) following intravitreal administration compared with the control group.
      Flow cytometry analysis revealed that more than 90% of the cells were viable, and
      only a low proportion of retinal cells presented apoptotic (~10%) or necrotic
      (<1%) activity across all groups. Molecular damage was also low with a maximum of
      6.4% DNA degradation observed in the comet assays. In addition, no increase in
      gene expression of apoptosis-inducing caspases was observed on retinal cells by
      qPCR in both the adalimumab and placebo groups compared with the control group.
      CONCLUSION: The use of adalimumab resulted in no detectable cytotoxicity or
      genotoxicity on retinal cells for up to 60 days upon administration. These
      results therefore indicate that adalimumab may be a safe option for intravitreal
      application to treat ocular inflammatory diseases in which TNF-alpha is involved.

PMID- 25945530
TI  - Preoperative automatic visual behavioural analysis as a tool for intraocular lens
      choice in cataract surgery.
AB  - PURPOSE: Cataract is the main cause of blindness, affecting 18 million people
      worldwide, with the highest incidence in the population above 50 years of age.
      Low visual acuity caused by cataract may have a negative impact on patient
      quality of life. The current treatment is surgery in order to replace the natural
      lens with an artificial intraocular lens (IOL), which can be mono- or multifocal.
      However, due to potential side effects, IOLs must be carefully chosen to ensure
      higher patient satisfaction. Thus, studies on the visual behavior of these
      patients may be an important tool to determine the best type of IOL implantation.
      This study proposed an anamnestic add-on for optimizing the choice of IOL.
      METHODS: We used a camera that automatically takes pictures, documenting the
      patient's visual routine in order to obtain additional information about the
      frequency of distant, intermediate, and near sights. RESULTS: The results
      indicated an estimated frequency percentage, suggesting that visual analysis of
      routine photographic records of a patient with cataract may be useful for
      understanding behavioural gaze and for choosing visual management strategy after
      cataract surgery, simultaneously stimulating interest for customized IOL
      manufacturing according to individual needs.

PMID- 25945531
TI  - Quercetin protects the retina by reducing apoptosis due to ischemia-reperfusion
      injury in a rat model.
AB  - PURPOSE: This study aimed to investigate the effect of quercetin on apoptotic
      cell death induced by ischemia-reperfusion (I/R) injury in the rat retina.
      METHODS: Twenty-four rats were divided into four equal groups: control, ischemic,
      solvent, and quercetin. I/R injury was achieved by elevating the intraocular
      pressure above the perfusion pressure. Intraperitoneal injections of 20 mg/kg of
      quercetin and dimethyl sulfoxide (DMSO) were performed in the quercetin and
      solvent groups, respectively, immediately prior to I/R injury, and the
      researchers allowed for the retinas to be reperfused. Forty-eight hours after
      injury, the thicknesses of the retinal ganglion cell layer (RGCL), inner nuclear
      layer (INL), inner plexiform layer (IPL), outer plexiform layer (OPL), and outer
      nuclear layer (ONL) were measured in all groups. Moreover, the numbers of
      terminal deoxynucleotidyl transferase dUTP nick-end-labeled [TUNEL (+)] cells and
      caspase-3 (+) cells in both INL and ONL were evaluated in all groups. RESULTS:
      The administration of quercetin was found to reduce the thinning of all retinal
      layers. The mean thickness of INL in the quercetin and ischemic groups was 21 +/-
      5.6 um and 16 +/- 6.4 um, respectively (P<0.05). Similarly, the mean thickness of
      ONL in the quercetin and ischemic groups was 50 +/- 12.8 um and 40 +/- 8.7 um,
      respectively (P<0.05). The antiapoptotic effect of quercetin in terms of reducing
      the numbers of both TUNEL (+) cells and caspase-3 (+) cells was significant in
      INL. The mean number of TUNEL (+) cells in INL in the ischemic and quercetin
      groups was 476.8 +/- 45.6/mm2 and 238.72 +/- 251/mm2, respectively (P<0.005). The
      mean number of caspase-3 (+) cells in INL of ischemic and quercetin groups was
      633.6 +/- 38.7/mm2 and 342.4 +/- 36.1/mm2, respectively (P<0.001). CONCLUSION:
      The use of quercetin may be beneficial in the treatment of retinal I/R injury
      because of its antiapoptotic effect on the retinal layers, particularly in INL.

PMID- 25945532
TI  - Optical coherence tomography and multifocal electroretinography of patients with
      advanced neovascular age-related macular degeneration before, during, and after
      treatment with ranibizumab.
AB  - PURPOSE: To evaluate retinal morphology and function of patients with advanced
      neovascular age-related macular degeneration (AMD) before, during, and after
      treatment with ranibizumab. METHODS: Twenty-one eyes diagnosed with advanced AMD
      were studied with optical coherence tomography (OCT) and multifocal
      electroretinography (mfERG). Three intravitreal injections of ranibizumab were
      administered at 1-month intervals. Evaluations were performed before the first
      injection (D0) and at 30 (D30), 60 (D60), and 90 days (D90) after the first
      injection and compared to an age-matched control group (n=21 eyes). RESULTS: The
      thickness of macular retinal layers increased before treatment due to the
      presence of intraretinal fluid. A thick retinal pigment epithelium
      choriocapillaris complex (RPE-CC) suggested the presence of choroidal neovascular
      membrane. Intraretinal edema decreased after treatment (P<0.01), but persisting
      RPE-CC thickness resulted in a subretinal scar. Three different annular retinal
      areas were studied with mfERG (from center to periphery: rings R1, R2, and R3).
      The amplitude of the first negative component (N1) decreased in R1, R2, and R3 at
      D30, D60, and D90 when compared with that in controls (P<0.05); the N1 implicit
      time was delayed in R3 at D30 (P<0.05). The amplitude of the first positive
      component (P1) was reduced in R1 and R2 at D30, D60, and D90 when compared with
      that in controls (P<0.01); the P1 implicit time was delayed in R1 at D0 and D60
      (P<0.05), in R2 at D0, D30, and D90 (P<0.01), and in R3 at D30 and D60 (P<0.05).
      CONCLUSION: Ranibizumab reduces intraretinal edema, even in advanced cases.
      Central macular activity appeared to increase after the initiation of treatment,
      improving over time.

PMID- 25945533
TI  - Impact of wildfire smoke in Buenos Aires, Argentina, on ocular surface.
AB  - PURPOSE: To evaluate the acute impact of the wildfire smoke episode in 2008 on
      the ocular surface of subjects living in the Metropolitan Area of Buenos Aires
      (MABA). METHODS: A total of 86 subjects were evaluated: Group 1 comprised
      patients from a public ophthalmology hospital (N=35) and Group 2 comprised
      healthy volunteers (N=51). All subjects answered a questionnaire on ocular
      symptoms and underwent ophthalmologic examination [bulbar conjunctival hyperemia,
      corneal fluorescein staining, rose bengal vital staining, tear break-up time
      (TBUT), Schirmer I test, tear lysozyme, and impression cytology] during and after
      the acute episode. Concentrations of carbon monoxide (CO), nitrogen dioxide
      (NO2), and particulate matter (PM) were measured before, during, and after the
      acute episode. RESULTS: Both groups showed a statically significant increase in
      ocular symptoms and bulbar conjunctival hyperemia and a statically significant
      decrease in tear break-up time during the acute episode. Group 1 showed more
      severe symptoms and a statistically significant increase in fluorescein and rose
      bengal staining intensities during the acute episode. We found a significant
      negative correlation between ocular symptoms and tear break-up time. During the
      episode, the levels of CO, NO2, and particulate matter in MABA were four times
      higher than the usual average levels for the same period in 2007 and 2009.
      CONCLUSIONS: Increased air pollution from the burning of biomass is associated
      with a decrease in the stability of the tear film (TBUT), generating areas of
      ocular surface exposure that may be the cause of the increased feeling of
      irritation. Group 1 was more affected by not having a healthy ocular surface, and
      thus consulted an ophthalmologist. Cytological changes in the conjunctiva were
      not observed, which could be due to the short duration of the episode.

PMID- 25945534
TI  - Bilateral acute iris transillumination (BAIT) initially misdiagnosed as acute
      iridocyclitis.
AB  - Bilateral acute iris transillumination (BAIT) is a relatively new clinical entity
      characterized by bilateral acute loss of iris pigment epithelium, iris
      transillumination, pigment dispersion in the anterior chamber, and sphincter
      paralysis. We report the case of a 30-year-old male who was initially diagnosed
      with acute iridocyclitis in a different clinic and treated with topical and
      systemic corticosteroids. He was referred to our clinic to seek another opinion
      because his symptoms did not improve. An ocular examination revealed bilateral
      pigment dispersion into the anterior chamber, diffuse iris transillumination,
      pigment dusting on the anterior lens capsule, atonic and distorted pupils, and
      increased intraocular pressure, suggesting a diagnosis of BAIT rather than
      iridocyclitis. Clinicians should be aware of the differential diagnosis of
      syndromes associated with pigment dispersion from iridocyclitis to avoid
      aggressive anti-inflammatory therapy and detailed investigation for uveitis. 

PMID- 25945535
TI  - Acute retinal necrosis following intravitreal dexamethasone (Ozurdex(r)) implant.
AB  - A 52-year-old woman undergoing azathioprine treatment for rheumatoid arthritis
      developed acute retinal necrosis a month after intravitreal dexamethasone
      (Ozurdex (r)) implantation for posterior uveitis in the left eye. Varicella
      zoster virus (VZV) DNA was detected in the anterior chamber and vitreous samples
      on polymerase chain reaction (PCR) analysis. Retinal detachment occurred despite
      systemic and intravitreal antiviral therapy. Favorable structural and functional
      outcomes were achieved after retinal surgery with silicone oil. To the authors'
      knowledge, this is the first reported case of acute retinal necrosis following
      placement of an Ozurdex(r) implant. Physicians practicing Ozurdex(r)
      implantations should be aware of this unusual but devastating complication. Extra
      caution and frequent follow-up are required in all immunocompromised patients
      receiving Ozurdex(r) implantation. 

PMID- 25945536
TI  - Macular dystrophy associated with Kjellin's syndrome: a case report.
AB  - Hereditary spastic paraplegia (HSP) is characterized by weakness and spasticity
      of the lower extremities. Kjellin's syndrome is a rare syndrome associated with
      HSP. The syndrome is characterized by the presence of bilateral retinal flecks,
      similar to the findings in Stargardt disease and fundus flavimaculatus. We report
      the case of a 34-year-old male who presented with complete features of Kjellin's
      syndrome, with typical retinal findings observed on multimodal imaging (spectral
      domain optical coherence tomography [SD-OCT], near-infrared reflectance and
      autofluorescence imaging). The ophthalmological changes at early stages of the
      disease may not impair visual acuity. Therefore, the detection of central retinal
      degeneration requires thorough fundus examination. 

PMID- 25945537
TI  - Oculo-peritoneal shunt: draining aqueous humor to the peritoneum.
AB  - In 2010, there were estimated to be approximately 60.5 million people with
      glaucoma. This number is expected to increase to 79.6 million by 2020. In 2010,
      there were 8.4 million people with bilateral blindness caused by glaucoma, and
      this number is expected in increase to 11.2 million by 2020. Filtering implants
      are special devices that have been developed to reduce intraocular pressure in
      patients with refractory glaucoma. The success rate of these implants is
      relatively low, and they continue to fail over time. To avoid failure caused by
      the formation of scar tissue around the implants, attempts have been made to
      drain the aqueous humor to various sites, including the venous system, lacrimal
      sac, sinuses, and conjunctival fornix. Recently, a system to shunt aqueous humor
      from the anterior chamber to the peritoneum has been developed. The surgical
      technique involved in this system is a modification of the technique currently
      used by neurosurgeons for the treatment of hydrocephalus. We present the first
      case operated using this technique. 

PMID- 25945539
TI  - A calipers-free intravitreal anti-VEGF injection technique.

PMID- 25945538
TI  - Impression cytology in the evaluation of ocular surface tumors: review article.
AB  - Impression cytology (IC) has been widely used as a method for evaluating the
      ocular surface and superficial cells layers in the diagnosis and follow-up after
      treatment of several ocular surface tumors of both epithelial and melanocytic
      origin. Information regarding this can be found in the English-language
      literature since 1992. Using either cellulose acetate or Biopore membranes for
      specimen collection, a high correlation has been found between IC and tissue
      histology. Compared with exfoliative cytology with spatula, IC is less traumatic
      to the patient's eye, provides a precise location of the area being studied, and
      allows accurate observation of the cells the way they exist in vivo. The
      additional advantage of IC is the preservation of limbal stem cells responsible
      for continuous corneal epithelium renewal; these can be affected after incisional
      or excisional biopsy at the corneoscleral limbus, which is the most frequent site
      of appearance of tumors in the stratified epithelium. Treatment for ocular
      surface squamous neoplasia has historically included surgery, but nonsurgical
      interventions have also been adopted. Hence, in certain cases, ophthalmologists
      may prefer interventions less invasive than surgical biopsy such as of impression
      cytology for both initial diagnosis and therapeutic monitoring of treatment for
      ocular surface lesions. Nevertheless, it should be considered that IC may be less
      helpful if the results conflict with the clinical picture or if the clinical
      diagnosis is uncertain and results are negative. In such cases, surgical biopsy
      is required for accurate diagnosis. The purpose of this review is to examine the
      published literature on the utilization of IC for the diagnosis and management of
      ocular surface tumors and to discuss the requirement for further investigation on
      the subject. 

PMID- 25945540
TI  - Dengue and chiasmal compression.

PMID- 25945541
TI  - Publish (negative results too) or perish.

PMID- 25945543
TI  - Bioinspired air-retaining nanofur for drag reduction.
AB  - Bioinspired nanofur, covered by a dense layer of randomly distributed high aspect
      ratio nano- and microhairs, possesses superhydrophobic and air-retaining
      properties. Nanofur is fabricated using a highly scalable hot pulling method in
      which softened polymer is elongated with a heated sandblasted plate. Here we
      investigate the stability of the underwater air layer retained by the irregular
      nanofur topography by applying hydraulic pressure to the nanofur kept underwater,
      and evaluate the gradual changes in the air-covered area. Furthermore, the drag
      reduction resulting from the nanofur air retention is characterized by measuring
      the pressure drop across channels with and without nanofur. 

PMID- 25945542
TI  - Regulating the stability and localization of CDK inhibitor p27(Kip1) via CSN6
      COP1 axis.
AB  - The COP9 signalosome subunit 6 (CSN6), which is involved in ubiquitin-mediated
      protein degradation, is overexpressed in many types of cancer. CSN6 is critical
      in causing p53 degradation and malignancy, but its target in cell cycle
      progression is not fully characterized. Constitutive photomorphogenic 1 (COP1) is
      an E3 ubiquitin ligase associating with COP9 signalosome to regulate important
      target proteins for cell growth. p27 is a critical G1 CDK inhibitor involved in
      cell cycle regulation, but its upstream regulators are not fully characterized.
      Here, we show that the CSN6-COP1 link is regulating p27(Kip1) stability, and that
      COP1 is a negative regulator of p27(Kip1). Ectopic expression of CSN6 can
      decrease the expression of p27(Kip1), while CSN6 knockdown leads to p27(Kip1)
      stabilization. Mechanistic studies show that CSN6 interacts with p27(Kip1) and
      facilitates ubiquitin-mediated degradation of p27(Kip1). CSN6-mediated p27
      degradation depends on the nuclear export of p27(Kip1), which is regulated
      through COP1 nuclear exporting signal. COP1 overexpression leads to the
      cytoplasmic distribution of p27, thereby accelerating p27 degradation.
      Importantly, the negative impact of COP1 on p27 stability contributes to
      elevating expression of genes that are suppressed through p27 mediation. Kaplan
      Meier analysis of tumor samples demonstrates that high COP1 expression was
      associated with poor overall survival. These data suggest that tumors with
      CSN6/COP1 deregulation may have growth advantage by regulating p27 degradation
      and subsequent impact on p27 targeted genes. 

PMID- 25945544
TI  - Chronic ciguatoxin treatment induces synaptic scaling through voltage gated
      sodium channels in cortical neurons.
AB  - Ciguatoxins are sodium channels activators that cause ciguatera, one of the most
      widespread nonbacterial forms of food poisoning, which presents with long-term
      neurological alterations. In central neurons, chronic perturbations in activity
      induce homeostatic synaptic mechanisms that adjust the strength of excitatory
      synapses and modulate glutamate receptor expression in order to stabilize the
      overall activity. Immediate early genes, such as Arc and Egr1, are induced in
      response to activity changes and underlie the trafficking of glutamate receptors
      during neuronal homeostasis. To better understand the long lasting neurological
      consequences of ciguatera, it is important to establish the role that chronic
      changes in activity produced by ciguatoxins represent to central neurons. Here,
      the effect of a 30 min exposure of 10-13 days in vitro (DIV) cortical neurons to
      the synthetic ciguatoxin CTX 3C on Arc and Egr1 expression was evaluated using
      real-time polymerase chain reaction approaches. Since the toxin increased the
      mRNA levels of both Arc and Egr1, the effect of CTX 3C in NaV channels, membrane
      potential, firing activity, miniature excitatory postsynaptic currents (mEPSCs),
      and glutamate receptors expression in cortical neurons after a 24 h exposure was
      evaluated using electrophysiological and western blot approaches. The data
      presented here show that CTX 3C induced an upregulation of Arc and Egr1 that was
      prevented by previous coincubation of the neurons with the NaV channel blocker
      tetrodotoxin. In addition, chronic CTX 3C caused a concentration-dependent shift
      in the activation voltage of NaV channels to more negative potentials and
      produced membrane potential depolarization. Moreover, 24 h treatment of cortical
      neurons with 5 nM CTX 3C decreased neuronal firing and induced synaptic scaling
      mechanisms, as evidenced by a decrease in the amplitude of mEPSCs and
      downregulation in the protein level of glutamate receptors that was also
      prevented by tetrodotoxin. These findings identify an unanticipated role for
      ciguatoxin in the regulation of homeostatic plasticity in central neurons
      involving NaV channels and raise the possibility that some of the neurological
      symptoms of ciguatera might be explained by these compensatory mechanisms.

PMID- 25945545
TI  - Black phosphorus gas sensors.
AB  - The utilization of black phosphorus and its monolayer (phosphorene) and few
      layers in field-effect transistors has attracted a lot of attention to this
      elemental two-dimensional material. Various studies on optimization of black
      phosphorus field-effect transistors, PN junctions, photodetectors, and other
      applications have been demonstrated. Although chemical sensing based on black
      phosphorus devices was theoretically predicted, there is still no experimental
      verification of such an important study of this material. In this article, we
      report on chemical sensing of nitrogen dioxide (NO2) using field-effect
      transistors based on multilayer black phosphorus. Black phosphorus sensors
      exhibited increased conduction upon NO2 exposure and excellent sensitivity for
      detection of NO2 down to 5 ppb. Moreover, when the multilayer black phosphorus
      field-effect transistor was exposed to NO2 concentrations of 5, 10, 20, and 40
      ppb, its relative conduction change followed the Langmuir isotherm for molecules
      adsorbed on a surface. Additionally, on the basis of an exponential conductance
      change, the rate constants for adsorption and desorption of NO2 on black
      phosphorus were extracted for different NO2 concentrations, and they were in the
      range of 130-840 s. These results shed light on important electronic and sensing
      characteristics of black phosphorus, which can be utilized in future studies and
      applications. 

PMID- 25945546
TI  - Incidentally Discovered Intraperitoneal Masses.

PMID- 25945549
TI  - Two stories of making a difference in Aerospace Medicine with AsMA.

PMID- 25945547
TI  - Weight expectations, motivations for weight change and perceived factors
      influencing weight management in young Australian women: a cross-sectional study.
AB  - OBJECTIVE: To examine young Australian women's weight expectations, motivations
      for weight change and perceived factors influencing weight management, and to
      determine if these factors differ by age, BMI, marital status, education or
      income. DESIGN: Cross-sectional study. An online survey captured respondents'
      weight, height, ideal weight, main reasons for wanting to change their weight and
      challenges to managing their weight. SETTING: Online survey in Australia.
      SUBJECTS: Six hundred and twenty women aged 18-30 years currently living in
      Australia who completed the survey between 31 July and 30 September 2012.
      RESULTS: Approximately half of participants (53.1 %) were a healthy weight, 25.2
      % overweight and 19.0 % obese. Women unhappy at their current weight (78.1 %)
      reported a median ideal weight -12.3 % less than their current weight. The key
      motivators for weight change were to improve health (24.4 %, ranked 1), feel
      better in oneself (22.3 %) and improve self-confidence (21.5 %). Lack of
      motivation, time constraints because of job commitments and cost were the most
      commonly reported factors influencing weight management. Age, BMI, marital
      status, education and income were found to influence weight expectations,
      motivations for weight change and/or factors perceived to influence weight
      management. CONCLUSIONS: The findings suggest potential implications for weight
      management interventions and public health messaging targeting young women, to
      improve long-term health outcomes. Strategies that promote the health benefits of
      physical activity and healthy eating, feeling better about oneself and improved
      self-confidence, and address the main factors influencing weight management
      including lack of motivation, time constraints and cost, may be used to engage
      this target group.

PMID- 25945550
TI  - Transcranial bright light and symptoms of jet lag: a randomized, placebo
      controlled trial.
AB  - BACKGROUND: Rapid travel over multiple time zones usually results in transient de
      synchronization between environmental time and the biological clock of the
      individual. Common symptoms are increased daytime sleepiness, reduced sleep
      duration and quality, and performance impairments. Exposure to ocular bright
      light is known to alleviate jet lag symptoms and facilitate adaptation to a new
      time zone. Recently, transcranial bright light (TBL) via the ear canals has been
      shown to have antidepressant, anxiolytic, and psychomotor performance-enhancing
      effects. In this case we studied whether intermittent TBL exposure can alleviate
      jet lag symptoms in a randomized, double-blind, placebo-controlled study.
      METHODS: Intermittent light exposures (4 * 12 min; day 0: 08:00, 10:00, 12:00,
      14:00; days 1-6: 10:00, 12:00, 14:00, 16:00) were administered during the 7-d
      post-travel period after an eastward transatlantic flight. The symptoms of jet
      lag were measured by the Visual Analog Scale (VAS), the Karolinska Sleepiness
      Scale (KSS), and the Profile of Mood States (POMS). RESULTS: We found a
      significant reduction of overall jet lag symptoms (VAS), subjective sleepiness
      (KSS), and the fatigue, inertia, and forgetfulness subscales of the POMS when
      comparing the active TBL treatment group (N = 30) to the placebo group (N = 25).
      For example, the normalized values of VAS in the TBL, but not the placebo, group
      returned to pre-travel levels by the final post-travel day (6.16 vs. 15.34).
      DISCUSSION: Results suggest a cumulative effect of TBL, as the effects emerged on
      post-travel days 3-4. Intermittent TBL seems to alleviate jet lag symptoms.

PMID- 25945551
TI  - Oxygen requirement to reverse altitude-induced hypoxemia with continuous flow and
      pulsed dose oxygen.
AB  - BACKGROUND: Hypoxemia secondary to reduced barometric pressure is a complication
      of ascent to altitude. We designed a study to compare the reversal of hypobaric
      hypoxemia at 14,000 ft with continuous flow oxygen from a cylinder and pulsed
      dose oxygen from a portable concentrator. METHODS: There were 30 healthy
      volunteers who were randomized to one of three study groups, placed in an
      altitude chamber, and ascended to 14,000 ft. There were 10 subjects in each study
      group. Subjects breathed room air for 10 min to induce hypoxemia. Oxygen was then
      delivered via a nasal cannula from a cylinder at 1, 2, or 3 lpm of continuous
      flow for 10 min. The subjects again breathed room air at altitude for 10 min and
      were then placed on pulsed dose oxygen and titrated to obtain the continuous flow
      Spo2 equivalent. Spo2, Etco2, RR, HR, Hgb, and tissue oxygenation (Sto2) were
      continuously recorded. RESULTS: The 1-lpm group's Spo2 range was 89-99%. The 2
      lpm group's Spo2 range was 95-98%, and the 3-lpm group's Spo2 range was 95-99%.
      The 2-lpm and 3-lpm flows were able to correct hypoxemia in every subject. The
      mean pulsed dose required to achieve an equivalent Spo2 ranged from 36.8 ml +/-
      18.9 ml in the 1-lpm arm, and 102.4 ml +/- 53.8 in the 3-lpm arm. CONCLUSIONS:
      Portable oxygen concentrators using pulsed dose technology corrected hypoxemia in
      every subject. Oxygen concentrators may be an alternative to liquid oxygen or
      cylinders for use during aeromedical evacuation.

PMID- 25945552
TI  - Cognitive and perceptual deficits of normobaric hypoxia and the time course to
      performance recovery.
AB  - BACKGROUND: Many in-flight hypoxia-like incidents involve exposure to normobaric
      hypoxia following an oxygen delivery equipment failure. Studies have documented
      the effect of hypoxia on specific aspects of human performance. The goal of the
      present study was to establish the effects of acute hypoxia on cognitive,
      psychomotor, and perceptual abilities and to chronicle the time required for
      these capabilities to fully recover to pre-exposure levels. METHODS: Subjects
      were presented with a battery of tests designed to assess visual acuity, contrast
      sensitivity, color vision, executive control, and reaction time (simple reaction
      time, SRT, and choice reaction time, CRT) before, during, immediately following,
      60 min, 120 min, and 24 h after hypoxic exposure. Oxygen saturation was
      continuously measured throughout the duration of the study using near-infrared
      spectroscopy measured on the forehead and finger pulse oximetry. RESULTS: During
      the course of six assessment periods, contrast sensitivity, color vision, and
      subjective workload were affected to varying degrees during hypoxic exposure, but
      returned to baseline levels soon after a return to normoxia. Conversely, reaction
      time values and regional cerebral oxygen saturation (MrSO2), while also affected
      during hypoxic exposure (MSRT = 362.17 ms, MCRT = 389.55 ms, MrSO2 = 79.36%), did
      not return to baseline levels (MSRT = 337.35 ms, MCRT = 372.75 ms, MrSO2 =
      99.75%) until the assessment period 24 h following exposure (MSRT = 324.35 ms,
      MCRT = 366.22 ms, MrSO2 = 99.10%). DISCUSSION: Evidence from this study suggests
      an impairment of specific performance characteristics following hypoxic exposure 
      some for a considerable period of time. Mitigation efforts should focus more on
      the prevention of hypoxia exposure rather than relying exclusively on training
      operators to recognize and react earlier to hypoxic symptomology.

PMID- 25945553
TI  - Prospective memory failures in aviation: effects of cue salience, workload, and
      individual differences.
AB  - INTRODUCTION: Prospective memory allows people to complete intended tasks in the
      future. Prospective memory failures, such as pilots forgetting to inform pattern
      traffic of their locations, can have fatal consequences. The present research
      examined the impact of system factors (memory cue salience and workload) and
      individual differences (pilot age, cognitive health, and expertise) on
      prospective memory for communication tasks in the cockpit. METHODS: Pilots (N =
      101) flew a Cessna 172 simulator at a non-towered aerodrome while maintaining
      communication with traffic and attending to flight parameters. Memory cue
      salience (the prominence of cues that signal an intended action) and workload
      were manipulated. Prospective memory was measured as radio call completion rates.
      RESULTS: Pilots' prospective memory was adversely affected by low-salience cues
      and high workload. An interaction of cue salience, pilots' age, and cognitive
      health reflected the effects of system and individual difference factors on
      prospective memory failures. For example, younger pilots with low levels of
      cognitive health completed 78% of the radio calls associated with low-salience
      memory cues, whereas older pilots with low cognitive health scores completed just
      61% of similar radio calls. DISCUSSION: Our findings suggest that technologies
      designed to signal intended future tasks should target those tasks with
      inherently low-salience memory cues. In addition, increasing the salience of
      memory cues is most likely to benefit pilots with lower levels of cognitive
      health in high-workload conditions.

PMID- 25945554
TI  - Infrared thermographic analysis of craniofacial muscles in military pilots
      affected by bruxism.
AB  - INTRODUCTION: Due to the physical stresses to which they are subjected, military
      pilots may experience bruxism, an "oral parafunction." Parafunction can cause
      masticatory muscle suffering and serious dental, periodontal, and
      temporomandibular joint damage. The aim of this pilot study was to analyze the
      temperature distribution in masticatory and upper trapezius muscles in a sample
      of bruxist air force pilots, to evaluate whether an occlusal splint would be able
      to induce skin temperature variations in the stomatognathic apparatus using the
      technology of infrared thermography. METHODS: A total of 11 male Italian Air
      Force pilots of high performance aircraft, ages from 27 to 40 yr (mean 34.91 +/-
      2.15 yr) with 1000-3000 flight hours, were enrolled in the study and analyzed
      using an infrared camera in order to evaluate the temperature of the masticatory
      muscles. All the recordings were taken on each subject using the same protocol
      with and without a temporary occlusal splint. RESULTS: The occlusal splint
      statistically increased each muscle temperature (0.10-0.20 degrees C) on both the
      sides of the body. No statistically significant differences were found between
      the left and right muscles (asymmetries) before or after the wearing of the
      splint except for the anterior temporalis muscle. No significant improvement or
      variations in temperature symmetry of this muscle was found after the application
      of the splint. DISCUSSION: The use of an occlusal splint could help in increasing
      muscles temperatures in Air Force pilots with consequent relaxation of their
      facial muscular system.

PMID- 25945555
TI  - A novel rescue-tube device for in-water resuscitation.
AB  - BACKGROUND: In-water resuscitation (IWR) is recommended in the 2010 guidelines of
      the European Resuscitation Council. As IWR represents a physical challenge to the
      rescuer, a novel Rescue Tube device with an integrated "Oxylator" resuscitator
      might facilitate IWR. The aim of the present study was the assessment of IWR
      using the novel Rescue Tube device. METHODS: Tidal and minute volumes were
      recorded using a modified Laerdal Resusci Anne mannequin. Furthermore, rescue
      time, water aspiration, submersions, and physical exertion were assessed. In this
      randomized cross-over trial, 17 lifeguards performed four rescue maneuvers over a
      100-m distance in open water in random order: no ventilation (NV), mouth-to-mouth
      ventilation (MMV), Oxylator-aided mask ventilation (OMV), and Oxylator-aided
      laryngeal tube ventilation (OLTV). RESULTS: OLTV resulted in effective
      ventilation over the entire rescue distance with the highest mean minute volumes
      (NV 0, MMV 2.9, OMV 4.1, OLTV 7.6 L . min(-1)). NV was the fastest rescue
      maneuver while IWR prolonged the rescue maneuver independently of the method of
      ventilation (mean total rescue time: NV 217, MMV 280, OMV 292, OLTV 290 s).
      Aspiration of substantial amounts of water occurred only during MMV (mean NV 20,
      MMV 215, OMV 15, OLTV 6 ml). NV and OLTV were rated as moderately challenging by
      the lifeguards, whereas MMV and OMV were rated as substantially demanding on a 0
      10 visual analog scale (NV 5.3, MMV 7.8, OMV 7.6, OLTV 5.9). DISCUSSION: The
      device might facilitate IWR by providing effective ventilation with minimal
      aspiration and by reducing physical effort. Another advantage is the possibility
      of delivering 100% oxygen.

PMID- 25945556
TI  - Acute spinal injury after centrifuge training in asymptomatic fighter pilots.
AB  - INTRODUCTION: Many countries have hypergravity training centers using centrifuges
      for pilots to cope with a high gravity (G) environment. The high G training
      carries potential risk for the development of spinal injury. However, no studies
      evaluated the influence of centrifuge training on the spines of asymptomatic
      fighter pilots on a large scale. METHODS: Study subjects were 991 male fighter
      pilots with high G training at one institution. Subject variables included
      information about physical characteristics, flight hours of pilots prior to the
      training, and G force exposure related factors during training. The two dependent
      variables were whether the pilots developed acute spinal injury after training
      and the severity of the injury (major/minor). RESULTS: The incidence of acute
      spinal injury after high G training was 2.3% (23 of 991 subjects). There were 19
      subjects who developed minor injury and 4 subjects who developed a herniated
      intervertebral disc, which is considered a major injury. In multivariate
      analysis, only the magnitude of G force during training was significantly related
      to the development of acute spinal injury. However, there was no significant
      factor related to the severity of the injury. DISCUSSION: These results suggest
      that high G training could cause negative effects on fighter pilots' spines. The
      magnitude of G force during training seemed to be the most significant factor
      affecting the occurrence of acute spinal injury.

PMID- 25945557
TI  - Altitude and seasonality impact on sleep in Antarctica.
AB  - BACKGROUND: This study investigates the effects of seasonality and altitude on
      sleep in extreme Antarctic conditions. METHODS: During summer and winter periods,
      24 h of actimetric recordings were obtained at two different research stations,
      Dumont d'Urville (sea level altitude) and Concordia (corrected altitude 12,467 ft
      or 3800 m). RESULTS: During daytime, there were no altitude- or season-related
      differences in time spent at work, energy expenditure, or number of walking
      steps. During the nighttime however, total sleep time was longer (m = 427.4; SD =
      42.4), sleep efficiency higher (m = 90; SD = 4.8), and wake after sleep onset
      shorter (m = 42.2; SD = 28.7) at sea level. Additionally, sleep fragmentation
      episodes and energy expenditure were higher during summer than winter periods.
      DISCUSSION: Our results show that dramatic variations in light exposure are not
      the only main factor affecting sleep quality in Antarctica, as altitude also
      markedly impacted sleep in these conditions. The effect of altitude-induced
      hypoxia should be taken into account in future investigations of sleep in extreme
      environments.

PMID- 25945558
TI  - Unpredictability of fighter pilots' g duration tolerance by anthropometric and
      physiological characteristics.
AB  - BACKGROUND: While the factors affecting fighter pilots' G level tolerance have
      been widely accepted, the factors affecting fighter pilots' G duration tolerance
      have not been well understood. METHODS: Thirty-eight subjects wearing anti-G
      suits were exposed to sustained high G forces using a centrifuge. The subjects
      exerted AGSM and decelerated the centrifuge when they reached the point of loss
      of peripheral vision. The G profile consisted of a +2.3 G onset rate, +7.3 G
      single plateau, and -1.6 G offset rate. Each subject's G tolerance time was
      recorded and the relationship between the tolerance time and the subject's
      anthropometric and physiological factors were analyzed. RESULTS: The mean
      tolerance time of the 38 subjects was 31.6 s, and the min and max tolerance times
      were 20 s and 58 s, respectively. The correlation analysis indicated that none of
      the factors had statistically significant correlations with the subjects' G
      duration tolerance. Stepwise multiple regression analysis showed that G duration
      tolerance was not dependent on any personal factors of the subjects. After the
      values of personal factors were simplified into 0 or 1, the t-test analysis
      showed that subjects' heights were inversely correlated with G duration tolerance
      at a statistically significant level. However, a logistic regression analysis
      suggested that the effect of the height factor to a pilot's G duration tolerance
      was too weak to be used as a predictor of a pilot's G tolerance. CONCLUSION:
      Fighter pilots' G duration tolerance could not be predicted by pilots'
      anthropometric and physiological factors.

PMID- 25945559
TI  - Neck pain in F-16 vs. Typhoon fighter pilots.
AB  - INTRODUCTION: In jet pilots, the neck is stressed by dynamic loading and there is
      growing concern about possible neck damage in pilots of new agile aircraft. Jet
      pilots often report neck pain after flight so intense that their operational
      capability may be affected. However, there is no clear evidence of structural
      damage related to the operational exposure. METHODS: We compared 35 F-16 pilots
      with 35 age-matched Eurofighter Typhoon pilots. All subjects completed an
      anonymous questionnaire on their flight activity and neck pain. RESULTS: The
      incidence of neck pain in the F-16 group was 48.6% compared with 5.7% of the
      Typhoon group, significantly higher. In F-16 pilots, there was a significant
      association between neck pain and age over 30 yr, total flight hours, and flight
      hours exceeding 600. DISCUSSION: Our findings suggest that the risk of neck pain
      after flight is higher among F-16 pilots compared with Typhoon pilots. This could
      be due to several reasons, including the backward reclined seat of the F-16,
      which exposes the neck to the load in an unfavorable posture while moving the
      head during maneuvers at sustained high-G.

PMID- 25945560
TI  - Tolerance of centrifuge-simulated suborbital spaceflight in subjects with
      implanted insulin pumps.
AB  - INTRODUCTION: With commercial spaceflight comes the possibility of spaceflight
      participants (SFPs) with significant medical conditions. Those with previously
      untested medical conditions, such as diabetes mellitus (DM) and the use of
      indwelling medical devices, represent a unique challenge. It is unclear how SFPs
      with such devices will react to the stresses of spaceflight. This case report
      describes two subjects with Type I DM using insulin pumps who underwent simulated
      dynamic phases of spaceflight via centrifuge G force exposure. CASE REPORT: Two
      Type I diabetic subjects with indwelling Humalog insulin pumps, a 23-yr-old man
      averaging 50 u of Humalog daily and a 27-yr-old man averaging 60 u of Humalog
      daily, underwent seven centrifuge runs over 48 h. Day 1 consisted of two +Gz runs
      (peak = +3.5 Gz, run 2) and two +Gx runs (peak = +6.0 Gx, run 4). Day 2 consisted
      of three runs approximating suborbital spaceflight profiles (combined +Gx and
      +Gz). Data collected included blood pressure, electrocardiogram, pulse oximetry,
      neurovestibular evaluation, and questionnaires regarding motion sickness,
      disorientation, greyout, and other symptoms. Neither subject experienced adverse
      clinical responses to the centrifuge exposure. Both maintained blood glucose
      levels between 110-206 mg . dl(-1). DISCUSSION: Potential risks to SFPs with
      insulin pump dependent DM include hypo/hyperglycemia, pump damage,
      neurovestibular dysfunction, skin breakdown, and abnormal stress responses. A
      search of prior literature did not reveal any previous studies of individuals
      with DM on insulin pumps exposed to prolonged accelerations. These cases suggest
      that individuals with conditions dependent on continuous medication delivery
      might tolerate the accelerations anticipated for commercial spaceflight.

PMID- 25945561
TI  - Centrifuge-simulated suborbital spaceflight in subjects with cardiac implanted
      devices.
AB  - INTRODUCTION: Future commercial spaceflight participants (SFPs) with conditions
      requiring personal medical devices represent a unique challenge. The behavior
      under stress of cardiac implanted devices (CIDs) such as pacemakers is of special
      concern. No known data currently exist on how such devices may react to the
      stresses of spaceflight. We examined the responses of two volunteer subjects with
      CIDs to G forces in a centrifuge to evaluate how similar potential commercial
      SFPs might tolerate the forces of spaceflight. CASE REPORT: Two subjects, 75- and
      79-yr-old men with histories of atrial fibrillation and implanted dual-lead, rate
      responsive pacemakers, underwent seven centrifuge runs over 2 d. Day 1 consisted
      of two +Gz runs (peak = +3.5 Gz, run 2) and two +Gx runs (peak = +6.0 Gx, run 4).
      Day 2 consisted of three runs approximating suborbital spaceflight profiles
      (combined +Gx/+Gz). Data collected included blood pressures, electrocardiograms,
      pulse oximetry, neurovestibular exams, and postrun questionnaires regarding
      motion sickness, disorientation, greyout, and other symptoms. Despite both
      subjects' significant medical histories, neither had abnormal physiological
      responses. Post-spin analysis demonstrated no lead displacement, damage, or
      malfunction of either CID. DISCUSSION: Potential risks to SFPs with CIDs include
      increased arrhythmogenesis, lead displacement, and device damage. There are no
      known prior studies of individuals with CIDs exposed to accelerations anticipated
      during the dynamic phases of suborbital spaceflight. These cases demonstrate that
      even individuals with significant medical histories and implanted devices can
      tolerate the acceleration exposures of commercial spaceflight. Further
      investigation will determine which personal medical devices present significant
      risks during suborbital flight and beyond.

PMID- 25945562
TI  - Letter to the Editor re: Pneumocephalus and neurosurgery in rotary aircrew:
      response.

PMID- 25945563
TI  - Letter to the Editor re: Pneumocephalus and neurosurgery in rotary aircrew:
      letter.

PMID- 25945564
TI  - You're the flight surgeon: eosinophilic esophagitis.
AB  - Ramage MH. You're the flight surgeon: eosinophilic esophagitis. Aerosp Med Hum
      Perform. 2015; 86(4):418-421. 

PMID- 25945565
TI  - You're the flight surgeon: myelolipoma.
AB  - Moore JL, Jackson CR, Ellis JC, Norrid C. You're the flight surgeon: myelolipoma.
      Aerosp Med Hum Perform. 2015; 86(4):421-423. 

PMID- 25945566
TI  - What makes a flight surgeon? The pre-world war I historical perspective.

PMID- 25945569
TI  - Structure of ginseng major latex-like protein 151 and its proposed
      lysophosphatidic acid-binding mechanism.
AB  - Lysophosphatidic acid (LPA) is a phospholipid growth factor with myriad effects
      on biological systems. LPA is usually present bound to animal plasma proteins
      such as albumin or gelsolin. When LPA complexes with plasma proteins, it binds to
      its cognate receptors with higher affinity than when it is free. Recently,
      gintonin from ginseng was found to bind to LPA and to activate mammalian LPA
      receptors. Gintonin contains two components: ginseng major latex-like protein 151
      (GLP) and ginseng ribonuclease-like storage protein. Here, the crystal structure
      of GLP is reported, which belongs to the plant Bet v 1 superfamily, and a model
      is proposed for how GLP binds LPA. Amino-acid residues of GLP recognizing LPA
      were identified using site-directed mutagenesis and isothermal titration
      calorimetry. The resulting GLP mutants were used to study the activation of LPA
      receptor-dependent signalling pathways. In contrast to wild-type GLP, the H147A
      mutant did not bind LPA, elicit intracellular Ca(2+) transients in neuronal cells
      or activate Ca(2+)-dependent Cl(-) channels in Xenopus oocytes. Based on these
      results, a mechanism by which GLP recognizes LPA and its requirement to activate
      G protein-coupled LPA receptors to elicit diverse biological responses were
      proposed. 

PMID- 25945570
TI  - Ambiguity assessment of small-angle scattering curves from monodisperse systems.
AB  - A novel approach is presented for an a priori assessment of the ambiguity
      associated with spherically averaged single-particle scattering. The approach is
      of broad interest to the structural biology community, allowing the rapid and
      model-independent assessment of the inherent non-uniqueness of three-dimensional
      shape reconstruction from scattering experiments on solutions of biological
      macromolecules. One-dimensional scattering curves recorded from monodisperse
      systems are nowadays routinely utilized to generate low-resolution particle
      shapes, but the potential ambiguity of such reconstructions remains a major
      issue. At present, the (non)uniqueness can only be assessed by a posteriori
      comparison and averaging of repetitive Monte Carlo-based shape-determination
      runs. The new a priori ambiguity measure is based on the number of distinct shape
      categories compatible with a given data set. For this purpose, a comprehensive
      library of over 14,000 shape topologies has been generated containing up to seven
      beads closely packed on a hexagonal grid. The computed scattering curves rescaled
      to keep only the shape topology rather than the overall size information provide
      a 'scattering map' of this set of shapes. For a given scattering data set, one
      rapidly obtains the number of neighbours in the map and the associated shape
      topologies such that in addition to providing a quantitative ambiguity measure
      the algorithm may also serve as an alternative shape-analysis tool. The approach
      has been validated in model calculations on geometrical bodies and its usefulness
      is further demonstrated on a number of experimental X-ray scattering data sets
      from proteins in solution. A quantitative ambiguity score (a-score) is introduced
      to provide immediate and convenient guidance to the user on the uniqueness of the
      ab initio shape reconstruction from the given data set.

PMID- 25945568
TI  - The solvent component of macromolecular crystals.
AB  - The mother liquor from which a biomolecular crystal is grown will contain water,
      buffer molecules, native ligands and cofactors, crystallization precipitants and
      additives, various metal ions, and often small-molecule ligands or inhibitors. On
      average, about half the volume of a biomolecular crystal consists of this mother
      liquor, whose components form the disordered bulk solvent. Its scattering
      contributions can be exploited in initial phasing and must be included in crystal
      structure refinement as a bulk-solvent model. Concomitantly, distinct electron
      density originating from ordered solvent components must be correctly identified
      and represented as part of the atomic crystal structure model. Herein, are
      reviewed (i) probabilistic bulk-solvent content estimates, (ii) the use of bulk
      solvent density modification in phase improvement, (iii) bulk-solvent models and
      refinement of bulk-solvent contributions and (iv) modelling and validation of
      ordered solvent constituents. A brief summary is provided of current tools for
      bulk-solvent analysis and refinement, as well as of modelling, refinement and
      analysis of ordered solvent components, including small-molecule ligands. 

PMID- 25945571
TI  - REdiii: a pipeline for automated structure solution.
AB  - High-throughput crystallographic approaches require integrated software solutions
      to minimize the need for manual effort. REdiii is a system that allows fully
      automated crystallographic structure solution by integrating existing
      crystallographic software into an adaptive and partly autonomous workflow engine.
      The program can be initiated after collecting the first frame of diffraction data
      and is able to perform processing, molecular-replacement phasing, chain tracing,
      ligand fitting and refinement without further user intervention. Preset values
      for each software component allow efficient progress with high-quality data and
      known parameters. The adaptive workflow engine can determine whether some
      parameters require modifications and choose alternative software strategies in
      case the preconfigured solution is inadequate. This integrated pipeline is
      targeted at providing a comprehensive and efficient approach to screening for
      ligand-bound co-crystal structures while minimizing repetitiveness and allowing a
      high-throughput scientific discovery process. 

PMID- 25945573
TI  - Identification of local variations within secondary structures of proteins.
AB  - Secondary-structure elements (SSEs) play an important role in the folding of
      proteins. Identification of SSEs in proteins is a common problem in structural
      biology. A new method, ASSP (Assignment of Secondary Structure in Proteins),
      using only the path traversed by the C(alpha) atoms has been developed. The
      algorithm is based on the premise that the protein structure can be divided into
      continuous or uniform stretches, which can be defined in terms of helical
      parameters, and depending on their values the stretches can be classified into
      different SSEs, namely alpha-helices, 310-helices, pi-helices, extended beta
      strands and polyproline II (PPII) and other left-handed helices. The methodology
      was validated using an unbiased clustering of these parameters for a protein data
      set consisting of 1008 protein chains, which suggested that there are seven well
      defined clusters associated with different SSEs. Apart from alpha-helices and
      extended beta-strands, 310-helices and pi-helices were also found to occur in
      substantial numbers. ASSP was able to discriminate non-alpha-helical segments
      from flanking alpha-helices, which were often identified as part of alpha-helices
      by other algorithms. ASSP can also lead to the identification of novel SSEs. It
      is believed that ASSP could provide a better understanding of the finer nuances
      of protein secondary structure and could make an important contribution to the
      better understanding of comparatively less frequently occurring structural
      motifs. At the same time, it can contribute to the identification of novel SSEs.
      A standalone version of the program for the Linux as well as the Windows
      operating systems is freely downloadable and a web-server version is also
      available at http://nucleix.mbu.iisc.ernet.in/assp/index.php. 

PMID- 25945572
TI  - Structures of Bacteroides fragilis uridine 5'-diphosphate-N-acetylglucosamine
      (UDP-GlcNAc) acyltransferase (BfLpxA).
AB  - Uridine 5'-diphosphate-N-acetylglucosamine (UDP-GlcNAc) acyltransferase (LpxA)
      catalyzes a reversible reaction for adding an O-acyl group to the GlcNAc in UDP
      GlcNAc in the first step of lipid A biosynthesis. Lipid A constitutes a major
      component of lipopolysaccharides, also referred to as endotoxins, which form the
      outer monolayer of the outer membrane of Gram-negative bacteria. Ligand-free and
      UDP-GlcNAc-bound crystal structures of LpxA from Bacteroides fragilis NCTC 9343,
      the most common pathogenic bacteria found in abdominal abscesses, have been
      determined and are presented here. The enzyme crystallizes in a cubic space
      group, with the crystallographic threefold axis generating the biological
      functional homotrimer and with each monomer forming a nine-rung left-handed beta
      helical (LbetaH) fold in the N-terminus followed by an alpha-helical motif in the
      C-terminus. The structure is highly similar to LpxA from other organisms. Yet,
      despite sharing a similar LbetaH structure with LpxAs from Escherichia coli and
      others, previously unseen calcium ions are observed on the threefold axis in B.
      fragilis LpxA to help stabilize the trimeric assembly. 

PMID- 25945574
TI  - Structural study of the X-ray-induced enzymatic reaction of octahaem cytochrome C
      nitrite reductase.
AB  - Octahaem cytochrome c nitrite reductase from the bacterium Thioalkalivibrio
      nitratireducens catalyzes the reduction of nitrite to ammonium and of sulfite to
      sulfide. The reducing properties of X-ray radiation and the high quality of the
      enzyme crystals allow study of the catalytic reaction of cytochrome c nitrite
      reductase directly in a crystal of the enzyme, with the reaction being induced by
      X-rays. Series of diffraction data sets with increasing absorbed dose were
      collected from crystals of the free form of the enzyme and its complexes with
      nitrite and sulfite. The corresponding structures revealed gradual changes
      associated with the reduction of the catalytic haems by X-rays. In the case of
      the nitrite complex the conversion of the nitrite ions bound in the active sites
      to NO species was observed, which is the beginning of the catalytic reaction. For
      the free form, an increase in the distance between the oxygen ligand bound to the
      catalytic haem and the iron ion of the haem took place. In the case of the
      sulfite complex no enzymatic reaction was detected, but there were changes in the
      arrangement of the active-site water molecules that were presumably associated
      with a change in the protonation state of the sulfite ions. 

PMID- 25945575
TI  - Against the odds? De novo structure determination of a pilin with two cysteine
      residues by sulfur SAD.
AB  - Exploiting the anomalous signal of the intrinsic S atoms to phase a protein
      structure is advantageous, as ideally only a single well diffracting native
      crystal is required. However, sulfur is a weak anomalous scatterer at the typical
      wavelengths used for X-ray diffraction experiments, and therefore sulfur SAD data
      sets need to be recorded with a high multiplicity. In this study, the structure
      of a small pilin protein was determined by sulfur SAD despite several obstacles
      such as a low anomalous signal (a theoretical Bijvoet ratio of 0.9% at a
      wavelength of 1.8 A), radiation damage-induced reduction of the cysteines and a
      multiplicity of only 5.5. The anomalous signal was improved by merging three data
      sets from different volumes of a single crystal, yielding a multiplicity of 17.5,
      and a sodium ion was added to the substructure of anomalous scatterers. In
      general, all data sets were balanced around the threshold values for a successful
      phasing strategy. In addition, a collection of statistics on structures from the
      PDB that were solved by sulfur SAD are presented and compared with the data.
      Looking at the quality indicator R(anom)/R(p.i.m.), an inconsistency in the
      documentation of the anomalous R factor is noted and reported.

PMID- 25945577
TI  - Development of a Thermofluor assay for stability determination of membrane
      proteins using the Na(+)/H(+) antiporter NhaA and cytochrome c oxidase.
AB  - Crystallization of membrane proteins is very laborious and time-consuming,
      yielding well diffracting crystals in only a minority of projects. Therefore, a
      rapid and easy method is required to optimize the conditions for initial
      crystallization trials. The Thermofluor assay has been developed as such a tool.
      However, its applicability to membrane proteins is still limited because either
      large hydrophilic extramembranous regions or cysteine residues are required for
      the available dyes to bind and therefore act as reporters in this assay. No probe
      has been characterized to discriminate between the hydrophobic surfaces of
      detergent micelles, folded and detergent-covered membrane proteins and denatured
      membrane proteins. Of the four dyes tested, the two dyes 1-anilinonaphthalene-8
      sulfonic acid (ANS) and SYPRO Orange were systematically screened for
      compatibility with five detergents commonly used in the crystallization of
      membrane proteins. ANS showed the weakest interactions with all of the detergents
      screened. It was possible to determine the melting temperature of the sodium
      ion/proton antiporter NhaA, a small membrane protein without large hydrophilic
      domains, over a broad pH range using ANS. Furthermore, cytochrome c oxidase (CcO)
      was used to apply the method to a four-subunit membrane protein complex. It was
      possible to obtain preliminary information on the temperature-dependent
      denaturation of this complex using the dye ANS. Application of the dye 7
      diethylamino-3-(4'-maleimidylphenyl)-4-methylcoumarin (CPM) to CcO in the
      Thermofluor assay enabled the determination of the melting temperatures of
      distinct subunits of the complex. 

PMID- 25945576
TI  - Structures of the Middle East respiratory syndrome coronavirus 3C-like protease
      reveal insights into substrate specificity.
AB  - Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic
      virus that causes severe respiratory illness accompanied by multi-organ
      dysfunction, resulting in a case fatality rate of approximately 40%. As found in
      other coronaviruses, the majority of the positive-stranded RNA MERS-CoV genome is
      translated into two polyproteins, one created by a ribosomal frameshift, that are
      cleaved at three sites by a papain-like protease and at 11 sites by a 3C-like
      protease (3 CL(pro)). Since 3 CL(pro) is essential for viral replication, it is a
      leading candidate for therapeutic intervention. To accelerate the development of
      3 CL(pro) inhibitors, three crystal structures of a catalytically inactive
      variant (C148A) of the MERS-CoV 3 CL(pro) enzyme were determined. The aim was to
      co-crystallize the inactive enzyme with a peptide substrate. Fortuitously,
      however, in two of the structures the C-terminus of one protomer is bound in the
      active site of a neighboring molecule, providing a snapshot of an enzyme-product
      complex. In the third structure, two of the three protomers in the asymmetric
      unit form a homodimer similar to that of SARS-CoV 3 CL(pro); however, the third
      protomer adopts a radically different conformation that is likely to correspond
      to a crystallographic monomer, indicative of substantial structural plasticity in
      the enzyme. The results presented here provide a foundation for the structure
      based design of small-molecule inhibitors of the MERS-CoV 3 CL(pro) enzyme.

PMID- 25945578
TI  - Three-dimensional structure and ligand-binding site of carp fishelectin (FEL).
AB  - Carp FEL (fishelectin or fish-egg lectin) is a 238-amino-acid lectin that can be
      purified from fish eggs by exploiting its selective binding to Sepharose followed
      by elution with N-acetylglucosamine. Its amino-acid sequence and other
      biochemical properties have previously been reported. The glycoprotein has four
      disulfide bridges and the structure of the oligosaccharides linked to Asn27 has
      been described. Here, the three-dimensional structures of apo carp FEL (cFEL) and
      of its complex with N-acetylglucosamine determined by X-ray crystallography at
      resolutions of 1.35 and 1.70 A, respectively, are reported. The molecule folds as
      a six-bladed beta-propeller and internal short consensus amino-acid sequences
      have been identified in all of the blades. A calcium atom binds at the bottom of
      the funnel-shaped tunnel located in the centre of the propeller. Two ligand
      binding sites, alpha and beta, are present in each of the two protomers in the
      dimer. The first site, alpha, is closer to the N-terminus of the chain and is
      located in the crevice between the second and the third blades, while the second
      site, beta, is located between the fourth and the fifth blades. The amino acids
      that participate in the contacts have been identified, as well as the conserved
      water molecules in all of the sites. Both sites can bind the two anomers, alpha
      and beta, of N-acetylglucosamine, as is clearly recognizable in the electron
      density maps. The lectin presents sequence homology to members of the tachylectin
      family, which are known to have a function in the innate immune system of
      arthropods, and homologous genes are present in the genomes of other fish and
      amphibians. This structure is the first of a protein of this group and, given the
      degree of homology with other members of the family, it is expected that it will
      be useful to experimentally determine other crystal structures using the
      coordinates of cFEL as a search probe in molecular replacement.

PMID- 25945579
TI  - Structural insight into the thermostable NADP(+)-dependent meso-diaminopimelate
      dehydrogenase from Ureibacillus thermosphaericus.
AB  - Crystal structures of the thermostable meso-diaminopimelate dehydrogenase (DAPDH)
      from Ureibacillus thermosphaericus were determined for the enzyme in the apo form
      and in complex with NADP(+) and N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic
      acid. The main-chain coordinates of the enzyme showed notable similarity to those
      of Symbiobacterium thermophilum DAPDH. However, the subunit arrangement of U.
      thermosphaericus DAPDH (a dimer) was totally different from that of the S.
      thermophilum enzyme (a hexamer). Structural comparison with the dimeric enzyme
      from the mesophile Corynebacterium glutamicum revealed that the presence of large
      numbers of intrasubunit and intersubunit hydrophobic interactions, as well as the
      extensive formation of intersubunit ion-pair networks, were likely to be the main
      factors contributing to the higher thermostability of U. thermosphaericus DAPDH.
      This differs from S. thermophilum DAPDH, within which the unique hexameric
      assembly is likely to be responsible for its high thermostability. Analysis of
      the active site of U. thermosphaericus DAPDH revealed the key factors responsible
      for the marked difference in substrate specificity between DAPDH and the D-amino
      acid dehydrogenase recently created from DAPDH by introducing five point
      mutations [Akita et al. (2012). Biotechnol. Lett. 34, 1693-1699; 1701-1702]. 

PMID- 25945580
TI  - Using support vector machines to improve elemental ion identification in
      macromolecular crystal structures.
AB  - In the process of macromolecular model building, crystallographers must examine
      electron density for isolated atoms and differentiate sites containing structured
      solvent molecules from those containing elemental ions. This task requires
      specific knowledge of metal-binding chemistry and scattering properties and is
      prone to error. A method has previously been described to identify ions based on
      manually chosen criteria for a number of elements. Here, the use of support
      vector machines (SVMs) to automatically classify isolated atoms as either solvent
      or one of various ions is described. Two data sets of protein crystal structures,
      one containing manually curated structures deposited with anomalous diffraction
      data and another with automatically filtered, high-resolution structures, were
      constructed. On the manually curated data set, an SVM classifier was able to
      distinguish calcium from manganese, zinc, iron and nickel, as well as all five of
      these ions from water molecules, with a high degree of accuracy. Additionally,
      SVMs trained on the automatically curated set of high-resolution structures were
      able to successfully classify most common elemental ions in an independent
      validation test set. This method is readily extensible to other elemental ions
      and can also be used in conjunction with previous methods based on a priori
      expectations of the chemical environment and X-ray scattering. 

PMID- 25945581
TI  - Structural and functional analysis of betaine aldehyde dehydrogenase from
      Staphylococcus aureus.
AB  - When exposed to high osmolarity, methicillin-resistant Staphylococcus aureus
      (MRSA) restores its growth and establishes a new steady state by accumulating the
      osmoprotectant metabolite betaine. Effective osmoregulation has also been
      implicated in the acquirement of a profound antibiotic resistance by MRSA.
      Betaine can be obtained from the bacterial habitat or produced intracellularly
      from choline via the toxic betaine aldehyde (BA) employing the choline
      dehydrogenase and betaine aldehyde dehydrogenase (BADH) enzymes. Here, it is
      shown that the putative betaine aldehyde dehydrogenase SACOL2628 from the early
      MRSA isolate COL (SaBADH) utilizes betaine aldehyde as the primary substrate and
      nicotinamide adenine dinucleotide (NAD(+)) as the cofactor. Surface plasmon
      resonance experiments revealed that the affinity of NAD(+), NADH and BA for
      SaBADH is affected by temperature, pH and buffer composition. Five crystal
      structures of the wild type and three structures of the Gly234Ser mutant of
      SaBADH in the apo and holo forms provide details of the molecular mechanisms of
      activity and substrate specificity/inhibition of this enzyme. 

PMID- 25945582
TI  - Structural insights into the binding of the human receptor for advanced glycation
      end products (RAGE) by S100B, as revealed by an S100B-RAGE-derived peptide
      complex.
AB  - S100B is a damage-associated molecular pattern protein that, when released into
      the extracellular milieu, triggers initiation of the inflammatory response
      through the receptor for advanced glycation end products (RAGE). Recognition of
      S100B is accomplished via the amino-terminal variable immunoglobulin domain (V
      domain) of RAGE. To gain insights into this interaction, a complex between S100B
      and a 15-amino-acid peptide derived from residues 54-68 of the V-domain was
      crystallized. The X-ray crystal structure was solved to 2.55 A resolution. There
      are two dimers of S100B and one peptide in the asymmetric unit. The binding
      interface of this peptide is compared with that found in the complex between
      S100B and the 12-amino-acid CapZ-derived peptide TRTK-12. This comparison reveals
      that although the peptides adopt completely different backbone structures, the
      residues buried at the interface interact with S100B in similar regions to form
      stable complexes. The binding affinities of S100B for the intact wild-type V
      domain and a W61A V-domain mutant were determined to be 2.7 +/- 0.5 and 1.3 +/-
      0.7 uM, respectively, using fluorescence titration experiments. These
      observations lead to a model whereby conformational flexibility in the RAGE
      receptor allows the adoption of a binding conformation for interaction with the
      stable hydrophobic groove on the surface of S100B.

PMID- 25945583
TI  - Raster-scanning serial protein crystallography using micro- and nano-focused
      synchrotron beams.
AB  - High-resolution structural information was obtained from lysozyme microcrystals
      (20 um in the largest dimension) using raster-scanning serial protein
      crystallography on micro- and nano-focused beamlines at the ESRF. Data were
      collected at room temperature (RT) from crystals sandwiched between two silicon
      nitride wafers, thereby preventing their drying, while limiting background
      scattering and sample consumption. In order to identify crystal hits, new multi
      processing and GUI-driven Python-based pre-analysis software was developed, named
      NanoPeakCell, that was able to read data from a variety of crystallographic image
      formats. Further data processing was carried out using CrystFEL, and the
      resultant structures were refined to 1.7 A resolution. The data demonstrate the
      feasibility of RT raster-scanning serial micro- and nano-protein crystallography
      at synchrotrons and validate it as an alternative approach for the collection of
      high-resolution structural data from micro-sized crystals. Advantages of the
      proposed approach are its thriftiness, its handling-free nature, the reduced
      amount of sample required, the adjustable hit rate, the high indexing rate and
      the minimization of background scattering.

PMID- 25945584
TI  - Tah1 helix-swap dimerization prevents mixed Hsp90 co-chaperone complexes.
AB  - Specific co-chaperone adaptors facilitate the recruitment of client proteins to
      the Hsp90 system. Tah1 binds the C-terminal conserved MEEVD motif of Hsp90, thus
      linking an eclectic set of client proteins to the R2TP complex for their assembly
      and regulation by Hsp90. Rather than the normal complement of seven alpha-helices
      seen in other tetratricopeptide repeat (TPR) domains, Tah1 unusually consists of
      the first five only. Consequently, the methionine of the MEEVD peptide remains
      exposed to solvent when bound by Tah1. In solution Tah1 appears to be
      predominantly monomeric, and recent structures have failed to explain how Tah1
      appears to prevent the formation of mixed TPR domain-containing complexes such as
      Cpr6-(Hsp90)2-Tah1. To understand this further, the crystal structure of Tah1 in
      complex with the MEEVD peptide of Hsp90 was determined, which shows a helix swap
      involving the fifth alpha-helix between two adjacently bound Tah1 molecules.
      Dimerization of Tah1 restores the normal binding environment of the bound Hsp90
      methionine residue by reconstituting a TPR binding site similar to that in seven
      helix-containing TPR domain proteins. Dimerization also explains how other
      monomeric TPR-domain proteins are excluded from forming inappropriate mixed co
      chaperone complexes. 

PMID- 25945585
TI  - The structure of a dual-specificity tyrosine phosphorylation-regulated kinase 1A
      PKC412 complex reveals disulfide-bridge formation with the anomalous catalytic
      loop HRD(HCD) cysteine.
AB  - Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a
      protein kinase associated with neuronal development and brain physiology. The
      DYRK kinases are very unusual with respect to the sequence of the catalytic loop,
      in which the otherwise highly conserved arginine of the HRD motif is replaced by
      a cysteine. This replacement, along with the proximity of a potential disulfide
      bridge partner from the activation segment, implies a potential for redox control
      of DYRK family activities. Here, the crystal structure of DYRK1A bound to PKC412
      is reported, showing the formation of the disulfide bridge and associated
      conformational changes of the activation loop. The DYRK kinases represent
      emerging drug targets for several neurological diseases as well as cancer. The
      observation of distinct activation states may impact strategies for drug
      targeting. In addition, the characterization of PKC412 binding offers new
      insights for DYRK inhibitor discovery. 

PMID- 25945586
TI  - Structural basis for the catalytic mechanism of homoserine dehydrogenase.
AB  - Homoserine dehydrogenase (HSD) is an oxidoreductase in the aspartic acid pathway.
      This enzyme coordinates a critical branch point of the metabolic pathway that
      leads to the synthesis of bacterial cell-wall components such as L-lysine and m
      DAP in addition to other amino acids such as L-threonine, L-methionine and L
      isoleucine. Here, a structural rationale for the hydride-transfer step in the
      reaction mechanism of HSD is reported. The structure of Staphylococcus aureus HSD
      was determined at different pH conditions to understand the basis for the
      enhanced enzymatic activity at basic pH. An analysis of the crystal structure
      revealed that Lys105, which is located at the interface of the catalytic and
      cofactor-binding sites, could mediate the hydride-transfer step of the reaction
      mechanism. The role of Lys105 was subsequently confirmed by mutational analysis.
      Put together, these studies reveal the role of conserved water molecules and a
      lysine residue in hydride transfer between the substrate and the cofactor. 

PMID- 25945587
TI  - Quiet about pain: experiences of Aboriginal people in two rural communities.
AB  - OBJECTIVE: This study explores communications experienced by Aboriginal people in
      health care encounters about pain. It examines barriers that can impact upon
      effective pain management for Aboriginal patients. (This article refers to
      Aboriginal people, as these were the study participants. It is not intended to
      exclude Torres Strait Islander people.) DESIGN: A qualitative study using focus
      groups. SETTING: Two Aboriginal communities in South East Queensland.
      PARTICIPANTS: The participants were 20 men and 20 women who identified a health
      condition with associated pain for which they had sought health care, including
      pain relief. Their conditions included arthritis, orthopaedic injuries, back pain
      and coronary artery disease. RESULTS: Physical pains associated with
      participants' health conditions were accorded a second place to deep emotional
      pain attributed to dispossession, dislocation and loss. At health facilities,
      prominent perceptions were that health professionals held a negative attitude
      towards them, and lacked respect and caring. Participants experienced that the
      language used by health professionals in consultations was complex. CONCLUSIONS:
      Aboriginal people often do not report pain, on the basis of previous negative
      encounters with the health system. Other perceived barriers to effective pain
      management included discriminatory attitudes of health professionals and
      communication problems.

PMID- 25945588
TI  - Pasireotide for the Medical Management of Feline Hypersomatotropism.
AB  - BACKGROUND: Feline hypersomatotropism (HST) is a cause of diabetes mellitus in
      cats. Pasireotide is a novel multireceptor ligand somatostatin analog that
      improves biochemical control of humans with HST. HYPOTHESIS/OBJECTIVES:
      Pasireotide improves biochemical control of HST and diabetes mellitus in cats.
      ANIMALS: Hypersomatotropism was diagnosed in diabetic cats with serum insulin
      like growth factor-1 (IGF-1) concentration >1,000 ng/mL by radioimmunoassay and
      pituitary enlargement. METHODS: Insulin-like growth factor 1 was measured and
      glycemic control assessed using a 12-hour blood glucose curve on days 1 and 5. On
      days 2, 3, and 4, cats received 0.03 mg/kg pasireotide SC q12h. IGF-1, insulin
      dose, and estimated insulin sensitivity (product of the area under the blood
      glucose curve [BGC] and insulin dose) were compared pre- and post treatment.
      Paired t-tests or Wilcoxon signed rank tests were employed for comparison where
      appropriate; a linear mixed model was created to compare BGC results. RESULTS:
      Insulin-like growth factor 1 decreased in all 12 cats that completed the study
      (median [range] day 1: 2,000 ng/mL [1,051-2,000] and day 5: 1,105 ng/mL [380
      1,727], P = .002, Wilcoxon signed rank test). Insulin dose was lower on day 5
      than on day 1 (mean reduction 1.3 [0-2.7] units/kg/injection, P = .003, paired t
      test). The product of insulin dose and area under the BGC was lower on day 5 than
      day 1 (difference of means: 1,912; SD, 1523; u * mg/dL * hours, P = .001; paired
      t-test). No clinically relevant adverse effects were encountered. CONCLUSIONS:
      Short-acting pasireotide rapidly decreased IGF-1 in cats with HST and insulin
      dependent diabetes. The decrease in IGF-1 was associated with increased insulin
      sensitivity.

PMID- 25945590
TI  - Editorial: a simple faecal preparation for faecal microbiota transplantation-
      authors' reply.

PMID- 25945589
TI  - MicroRNA-132/212 family enhances arteriogenesis after hindlimb ischaemia through
      modulation of the Ras-MAPK pathway.
AB  - Arteriogenesis is a complicated process induced by increased local shear-and
      radial wall-stress, leading to an increase in arterial diameter. This process is
      enhanced by growth factors secreted by both inflammatory and endothelial cells in
      response to physical stress. Although therapeutic promotion of arteriogenesis is
      of great interest for ischaemic diseases, little is known about the modulation of
      the signalling cascades via microRNAs. We observed that miR-132/212 expression
      was significantly upregulated after occlusion of the femoral artery. miR-132/212
      knockout (KO) mice display a slower perfusion recovery after hind-limb ischaemia
      compared to wildtype (WT) mice. Immunohistochemical analysis demonstrates a clear
      trend towards smaller collateral arteries in KO mice. Although Ex vivo aortic
      ring assays score similar number of branches in miR-132/212 KO mice compared to
      WT, it can be stimulated with exogenous miR-132, a dominant member of the miR
      132/212 family. Moreover, in in vitro pericyte-endothelial co-culture cell
      assays, overexpression of miR-132 and mir-212 in endothelial cells results in
      enhanced vascularization, as shown by an increase in tubular structures and
      junctions. Our results suggested that miR-132/212 may exert their effects by
      enhancing the Ras-Mitogen-activated protein kinases MAPK signalling pathway
      through direct inhibition of Rasa1, and Spred1. The miR-132/212 cluster promotes
      arteriogenesis by modulating Ras-MAPK signalling via direct targeting of its
      inhibitors Rasa1 and Spred1.

PMID- 25945592
TI  - Congenital Bilateral Retinal Detachment in Two Siblings with Osteoporosis
      Pseudoglioma Syndrome.
AB  - The birth of a bilaterally blind child is catastrophic for families and a
      challenging diagnostic and management problem for ophthalmologists. Early
      identification of the underlying cause and its genetic basis helps initiate
      possible treatment, delineate prognosis, and identify risks for future
      pregnancies. In some cases, an early diagnosis can also influence the treatment
      of other family members. We report two sisters with bilateral retinal detachment
      and retro-lental masses from birth with no detectable NDP or FZD4 mutations. They
      were born to parents without detectable retinal anomalies. At 1 year of age, the
      elder sister had low impact bone fractures, and further evaluation identified
      severe osteopenia and multiple spinal compression fractures. Molecular testing
      identified biallelic lipoprotein receptor-related protein 5 (LRP5) mutations
      (NM_002335.3:c. [889dupA]; [2827 + 1G > A]) confirming a diagnosis of
      osteoporosis-pseudoglioma (OPPG) syndrome. After this diagnosis, the father and
      mother were found to have low bone mass and the father started on therapy. We
      conclude that early detection of LRP5 mutations is important for initiation of
      treatment of reduced bone density in the patients and their carrier relatives.

PMID- 25945593
TI  - Differentiated thyroid cancer in people aged 85 and older.
AB  - OBJECTIVES: To describe the characteristics and treatment patterns of
      differentiated thyroid cancer in older adults. DESIGN: Retrospective cohort
      study. SETTING: The National Cancer Institute Surveillance, Epidemiology, and End
      Results database. PARTICIPANTS: Individuals age 85 and older with a primary
      thyroid cancer diagnosis of papillary or follicular histology diagnosed between
      1988 and 2007 (N=424). MEASUREMENTS: Age, sex, histology, extent of disease,
      tumor size, treatment, type of surgery, cause of death, and length of survival.
      RESULTS: Tumor size and extent of disease were significantly related to cause of
      death (P=.02). Participants who did not have surgery were more likely to die of
      their thyroid cancer than of any other cause (P=.01), and whether a participant
      had surgery was significantly related to age (P=.002). Participants who had
      surgery had significantly longer survival than those who did not (P<.001). Type
      of surgery (P=.92) and adding radioactive iodine after surgery (P=.07) did not
      appear to influence length of survival. CONCLUSION: Although differentiated
      thyroid cancer is typically considered a relatively indolent disease, this is not
      the case in older adults. Surgery appears to reduce the likelihood of death from
      thyroid cancer in this population and confers a survival benefit. Type of surgery
      and adding radioactive iodine therapy do not seem to improve the survival benefit
      of surgical management.

PMID- 25945591
TI  - Novel scoring system and algorithm for classifying chronic rhinosinusitis: the
      JESREC Study.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) can be classified into CRS with nasal
      polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRSwNP displays more
      intense eosinophilic infiltration and the presence of Th2 cytokines. Mucosal
      eosinophilia is associated with more severe symptoms and often requires multiple
      surgeries because of recurrence; however, even in eosinophilic CRS (ECRS),
      clinical course is variable. In this study, we wanted to set objective clinical
      criteria for the diagnosis of refractory CRS. METHODS: This was a retrospective
      study conducted by 15 institutions participating in the Japanese Epidemiological
      Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC). We evaluated
      patients with CRS treated with endoscopic sinus surgery (ESS), and risk of
      recurrence was estimated using Cox proportional hazard models. Multiple logistic
      regression models and receiver operating characteristics curves were constructed
      to create the diagnostic criterion for ECRS. RESULTS: We analyzed 1716 patients
      treated with ESS. To diagnose ECRS, the JESREC scoring system assessed unilateral
      or bilateral disease, the presence of nasal polyps, blood eosinophilia, and
      dominant shadow of ethmoid sinuses in computed tomography (CT) scans. The cutoff
      value of the score was 11 points (sensitivity: 83%, specificity: 66%). Blood
      eosinophilia (>5%), ethmoid sinus disease detected by CT scan, bronchial asthma,
      aspirin, and nonsteroidal anti-inflammatory drugs intolerance were associated
      significantly with recurrence. CONCLUSION: We subdivided CRSwNP in non-ECRS,
      mild, moderate, and severe ECRS according to our algorithm. This classification
      was significantly correlated with prognosis. It is notable that this algorithm
      may give useful information to clinicians in the refractoriness of CRS before ESS
      or biopsy.

PMID- 25945595
TI  - Graphene Oxide Based Nanocarrier Combined with a pH-Sensitive Tracer: A Vehicle
      for Concurrent pH Sensing and pH-Responsive Oligonucleotide Delivery.
AB  - We chemically tuned the oxidation status of graphene oxide (GO) and constructed a
      GO-based nanoplatform combined with a pH-sensitive fluorescence tracer that is
      designed for both pH sensing and pH-responsive drug delivery. A series of GOs
      oxidized to distinct degrees were examined to optimize the adsorption of the
      model drug, poly dT30. We determined that highly oxidized GO was a superior drug
      carrier candidate in vitro when compared to GOs oxidized to lesser degrees. In
      the cell experiment, the synthesized pH-sensitive rhodamine dye was first applied
      to monitor cellular pH; under acidic conditions, protonated rhodamine fluoresces
      at 588 nm (lambdaex=561 nm). When the dT30-GO nanocarrier was introduced into
      cells, a rhodamine-triggered competition reaction occurred, and this led to the
      release of the oligonucleotides and the quenching of rhodamine fluorescence by
      GO. Our results indicate high drug loading (FAM-dT30/GO=25/50 MUg/mL) and rapid
      cellular uptake (<0.5 h) of the nanocarrier which can potentially be used for
      targeted RNAi delivery to the acidic milieu of tumors.

PMID- 25945594
TI  - Host Response to the Lung Microbiome in Chronic Obstructive Pulmonary Disease.
AB  - RATIONALE: The relatively sparse but diverse microbiome in human lungs may become
      less diverse in chronic obstructive pulmonary disease (COPD). This article
      examines the relationship of this microbiome to emphysematous tissue destruction,
      number of terminal bronchioles, infiltrating inflammatory cells, and host gene
      expression. METHODS: Culture-independent pyrosequencing microbiome analysis was
      used to examine the V3-V5 regions of bacterial 16S ribosomal DNA in 40 samples of
      lung from 5 patients with COPD (Global Initiative for Chronic Obstructive Lung
      Disease [GOLD] stage 4) and 28 samples from 4 donors (controls). A second
      protocol based on the V1-V3 regions was used to verify the bacterial microbiome
      results. Within lung tissue samples the microbiome was compared with results of
      micro-computed tomography, infiltrating inflammatory cells measured by
      quantitative histology, and host gene expression. MEASUREMENTS AND MAIN RESULTS:
      Ten operational taxonomic units (OTUs) was found sufficient to discriminate
      between control and GOLD stage 4 lung tissue, which included known pathogens such
      as Haemophilus influenzae. We also observed a decline in microbial diversity that
      was associated with emphysematous destruction, remodeling of the bronchiolar and
      alveolar tissue, and the infiltration of the tissue by CD4(+) T cells. Specific
      OTUs were also associated with neutrophils, eosinophils, and B-cell infiltration
      (P < 0.05). The expression profiles of 859 genes and 235 genes were associated
      with either enrichment or reductions of Firmicutes and Proteobacteria,
      respectively, at a false discovery rate cutoff of less than 0.1. CONCLUSIONS:
      These results support the hypothesis that there is a host immune response to
      microorganisms within the lung microbiome that appears to contribute to the
      pathogenesis of COPD.

PMID- 25945596
TI  - The Role of OmpK35, OmpK36 Porins, and Production of beta-Lactamases on Imipenem
      Susceptibility in Klebsiella pneumoniae Clinical Isolates, Cairo, Egypt.
AB  - BACKGROUND: OmpK35 and OmpK36 are the major outer membrane porins of Klebsiella
      pneumoniae. We aimed to study the effect of combined porin loss and production of
      extended-spectrum beta-lactamases (ESBLs) on imipenem susceptibility among K.
      pneumoniae clinical isolates. MATERIALS AND METHODS: This study included 91
      suspected ESBL-producing K. pneumoniae clinical isolates, isolated from different
      patient specimens at the Cairo University hospital from January to June 2010. All
      isolates were subjected to genotypic analysis of the outer membrane protein gene
      expression using reverse transcription-PCR (RT-PCR) and analysis of OmpK35/36 of
      38 isolates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE). RESULTS: By RT-PCR, loss of Omp35 was detected in 78 (85.7%) isolates,
      loss of Omp36 was detected in 64 (70.32%), and loss of both porins was detected
      in 62 (68.1%). Out of 91 isolates, 45 (49.5%) were resistant to cefoxitin, and 17
      (18.7%) were confirmed as derepressed AmpC producers. Omp35 was lost in all FOX
      resistant isolates, whereas Omp36 was lost in 42 (93.3%) (p-value 0.002). The
      mean of ceftazidime inhibition zone diameter was significantly decreased among
      ESBL-producing isolates with loss of Omp35/36 (p-value 0.041 and 0.006),
      respectively. The mean of imipenem minimal inhibitory concentration (MIC) was
      markedly increased to 8.55 MUg/ml among AmpC-producing isolates with Omp35/36
      loss, while the mean of imipenem MIC among the 66 confirmed ESBL producers was
      0.32 MUg/ml. CONCLUSION: Imipenem MIC was markedly increased among K. pneumoniae
      isolates showing AmpC production with loss of both porins OmpK35/36. Meanwhile,
      the association of porin OmpK35/36 loss with ESBL production was not a direct
      cause of resistance to imipenem.

PMID- 25945598
TI  - Rhenium-Catalyzed [4 + 1] Annulation of Azobenzenes and Aldehydes via Isolable
      Cyclic Rhenium(I) Complexes.
AB  - The first Re-catalyzed [4 + 1] annulation of azobenzenes with aldehydes was
      developed to furnish 2H-indazoles via isolable and characterized cyclic Re(I)
      complexes. For the first time, the acetate-acceleration effect is showcased in Re
      catalyzed C-H activation reactions. Remarkably, mechanistic studies revealed an
      irreversible aldehyde-insertion step, which is in sharp contrast to those of
      previous Rh- and Co-systems. 

PMID- 25945597
TI  - Feasibility of a pocket-PC based cognitive control intervention in dementia
      spousal caregivers.
AB  - OBJECTIVES: Spousal caregivers of patients with dementia are in need of
      interventions to bolster their quality of life. Computer-based, self-administered
      cognitive training is an innovative approach to target spousal caregiver distress
      and coping. We tested the feasibility of administering one such intervention with
      minimal clinician intervention. METHODS: Twenty-seven elderly adults (>64 years
      old), who each were the primary caregiver for a spouse with dementia, were
      recruited through the Memory Disorders Clinic of the Alzheimer Disease Research
      Center in Pittsburgh, PA. Spousal caregivers were instructed to use a handheld
      computer version of the Adaptive Paced Visual Serial Attention Task (APVSAT) at
      least three times per week for four weeks as part of a larger caregiver
      intervention trial (P01 AG020677). Feasibility was explored by examining the
      frequency of APVSAT usage. RESULTS: Results suggest that self-directed cognitive
      training is feasible for spousal caregivers of dementia patients. The mean usage
      of the APVSAT was 42 (SD = 28.58). Performance increased from the beginning to
      the end of the trial, and usage was not affected by stress, worry, or poor sleep
      quality. CONCLUSION: Findings suggest the potential utility of cognitive training
      via handheld computer for spousal caregivers of dementia patients to improve
      problem solving, coping and adaptation, planning, and persevering with goal
      directed tasks.

PMID- 25945599
TI  - Fitter Students or Flabbier Standards? Thoughts and Reflection on the Findings of
      a Recent Chinese Fitness Study.
AB  - It was widely reported in China that female college students were fitter than
      male college students in a recent fitness study in Jiangsu Province, China. After
      carefully examining the finding and its related context, I believe that this
      specific finding was a "side effect" of the changes made in the 2014 Chinese
      Students Fitness and Health Standards rather than true improvements in female
      students' fitness. I further verified my observation using data from the 2010 and
      2014 fitness studies from another province in China. After describing the lessons
      learned, I call for more studies to examine the validity and credibility of the
      2014 standards and suggest using caution when releasing any new standards in the
      future before they are carefully studied and evaluated.

PMID- 25945600
TI  - Surfactant-Induced Artifacts during Proteomic Sample Preparation.
AB  - Bottom-up proteomics is a powerful tool for characterization of protein post
      translational modifications (PTMs), where PTMs are identified at the peptide
      level by mass spectrometry (MS) following protein digestion. However, enzymatic
      digestion is associated with additional sample processing steps that may
      potentially introduce artifactual modifications. Here, during an MS study of the
      PTMs of the regulator of G-protein signaling 4, we discovered that the use of
      ProteaseMAX, which is an acid-labile surfactant commonly used to improve protein
      solubilization and digestion efficiency, can lead to in vitro modifications on
      cysteine residues. These hydrophobic modifications resemble S-palmitoylation and
      hydroxyfarnesylation, thus discouraging the use of ProteaseMAX in studies of
      lipid modifications of proteins. Furthermore, since they target the cysteine
      thiol group, the presence of these artifacts will inevitably lead to inaccuracies
      in quantitative analysis of cysteine modifications. 

PMID- 25945602
TI  - Urine neutrophil gelatinase associated lipocalin as an early marker of acute
      kidney injury in hematopoietic stem cell transplantation patients.
AB  - Acute kidney injury (AKI) is common in hematopoietic stem cell transplantation
      (HSCT) patients with an incidence of 21-73%. Prevention and early diagnosis
      reduces the frequency and severity of this complication. Predictive biomarkers
      are of major importance to timely diagnosis. Neutrophil gelatinase associated
      lipocalin (NGAL) is a widely investigated novel biomarker for early diagnosis of
      AKI. However, no study assessed NGAL for AKI diagnosis in HSCT patients. We
      performed further analyses on gathered data from our recent trial to evaluate the
      performance of urine NGAL (uNGAL) as an indicator of AKI in 72 allogeneic HSCT
      patients. AKI diagnosis and severity were assessed using Risk-Injury-Failure-Loss
      End-stage renal disease and AKI Network criteria. We assessed uNGAL on days -6, 
      3, +3, +9 and +15. Time-dependent Cox regression analysis revealed a
      statistically significant relationship between uNGAL and AKI occurrence. (HR =
      1.04 (1.008-1.07), p = 0.01). There was a relation between uNGAL day + 9 to
      baseline ratio and incidence of AKI (unadjusted HR = 1.047 (1.012-1.083), p <
      0.01). The area under the receiver-operating characteristic curve for day + 9 to
      baseline ratio was 0.86 (0.74-0.99, p < 0.01) and a cut-off value of 2.62 was 85%
      sensitive and 83% specific in predicting AKI. Our results indicated that increase
      in uNGAL augmented the risk of AKI and the changes of day +9 uNGAL concentrations
      from baseline could be of value for predicting AKI in HSCT patients. Additionally
      uNGAL changes preceded serum Cr raises by nearly 2 days.

PMID- 25945603
TI  - A retrospective study of palindrome symmetrical-tip catheters for chronic
      hemodialysis access in China.
AB  - Hemodialysis catheters remain necessary for long-term vascular access in patients
      for whom arteriovenous access may be problematic or impossible. Developments in
      catheter design have improved long-term catheter functionality, and reduced the
      rate of infection and complications associated with their use. This retrospective
      study of 284 cases of chronic catheterization in 271 patients treated between
      2009 and 2011 using Tal PalindromeTM symmetrical-tip (N = 118) or QuintonTM
      PermcathTM step-tip (N = 166) hemodialysis catheters evaluates the efficacy and
      the safety of symmetrical-tip dialysis catheters for chronic hemodialysis,
      compared with a step-tip catheter. Measurements of catheter performance included
      mean catheter dwell time, incidence of low blood flow, and rates of infection and
      catheter-related blood stream infection (CRBSI). The symmetrical-tip catheter had
      a significantly longer mean dwell time compared with the step-tip catheter; 329.4
      +/- 38.1 versus 273.1 +/- 25.4 d (p < 0.05). In addition, the rate of occurrence
      of low blood flow per 1000 catheter days was lower for the symmetrical-tip
      compared with the step-tip catheter; 1.13 versus 6.86 (p < 0.01). The symmetrical
      tip catheter was also associated with a lower incidence of complications; the
      rates of infection (0.28 vs. 0.78; p < 0.01) and CRBSI (0.15 vs. 0.44; p < 0.01)
      were lower compared with those for step-tip catheters, and catheter removal
      occurred less often for the symmetrical-tip catheter (8% vs. 16%; p < 0.05). The
      symmetrical-tip hemodialysis catheter was associated with a longer mean dwell
      time, lower incidence of low blood flow, and lower infection rate compared with
      the step-tip catheter.

PMID- 25945604
TI  - Inflammation is associated to volume status in peritoneal dialysis patients.
AB  - AIM: The aim of this study is to investigate whether there is a relationship
      between inflammation and volume status in patients underwent peritoneal dialysis
      (PD). PATIENTS AND METHOD: This cross-sectional study included 159 PD patients.
      The median duration of PD was 17 (range, 1-151) months. All patients were
      examined using bioelectrical impedance analysis to estimate the ratio of
      extracellular water to total body water (ECW/TBW), which was used to assess their
      volume status. The patients were categorized as having one of the following three
      volume statuses: hypervolemic (above +2 SD from the mean, which was obtained from
      healthy controls), normovolemic (between +2 SD and -2 SD), or hypovolemic (below 
      2 SD from the mean). Five patients with hypovolemia were excluded from the study.
      Fifty-six patients were hypervolemic whereas 98 patients were euvolemic. High
      sensitive C-reactive protein (hs-CRP) levels were measured to evaluate
      inflammation in all patients. RESULTS: hs-CRP value levels were significantly
      higher in hypervolemic patients compared with euvolemic patients [7.1 (3.1-44.0)
      mg/L vs. 4.3 (3.1-39.6), p: 0.015, respectively]. Left ventricular hypertrophy
      was more frequent in hypervolemic patients compared with euvolemic patients
      (53.6% vs. 30.6%, p: 0.004, respectively). ECW/TBW ratio positively correlated
      with hs-CRP (r: 0.166, p: 0.039). Gender, hs-CRP, and residual Kt/V urea were
      found to be independent risk factors for hypervolemia in multivariate analysis.
      CONCLUSION: Inflammation is associated with hypervolemia in PD patients. Residual
      renal functions play an important role to maintain euvolemia in PD patients.

PMID- 25945605
TI  - High serum chemerin level in CKD patients is related to kidney function, but not
      to its adipose tissue overproduction.
AB  - Chemerin is an adipokine modulating inflammatory response and affecting glucose
      and lipid metabolism. These disturbances are common in CKD. The aim of the study
      was: (a) to evaluate circulating chemerin level at different stages of CKD; (b)
      to measure subcutaneous adipose tissue chemerin gene expression; (c) to estimate
      the efficiency of renal replacement therapy in serum chemerin removal. 187
      patients were included into the study: a) 58 patients with CKD; (b) 29 patients
      on hemodialysis; (c) 20 patients after kidney transplantation. 80 subjects
      constituted control group. Serum chemerin concentration was estimated by ELISA.
      The adipose tissue chemerin mRNA level was measured by RT-qPCR. The mean serum
      chemerin concentration in CKD patients was 70% higher than in the control group
      (122.9 +/- 33.7 vs. 72.6 +/- 20.7 ng/mL; p < 0.001) and it negatively correlated
      with eGFR (r = -0.71, p < 0.001). The equally high plasma chemerin level was
      found in HD patients and a HD session decreased it markedly (115.7 +/- 17.6 vs.
      101.5 +/- 16.4 ng/mL; p < 0.001). Only successful kidney transplantation allowed
      it to get down to the values noted in controls (74.8 +/- 16.0 vs. 72.6 +/- 20.7
      ng/mL; n.s.). The level of subcutaneous adipose tissue chemerin mRNA in CKD
      patients was not different than in patients of the control group. The study
      demonstrates that elevated serum chemerin concentration in CKD patients: (a) is
      related to kidney function, but not to increased chemerin production by
      subcutaneous adipose tissue, and (b) it can be efficiently corrected by
      hemodialysis treatment and normalized by kidney transplantation.

PMID- 25945606
TI  - Urine matrix metalloproteinases and their extracellular inducer EMMPRIN in
      children with chronic kidney disease.
AB  - BACKGROUND: Transforming growth factor (TGF)beta1 and matrix metalloproteinases
      (MMPs) play an essential role in CKD-related tissue remodeling. However, there
      are no data on urine MMPs and their extracellular inducer EMMPRIN in CKD
      patients. The aim of study was to assess the concentrations of MMP-2, MMP-7, MMP
      9, EMMPRIN and TGFbeta1 in serum and urine of CKD children and to analyze the
      potential relations between those parameters. METHODS: Forty-one pre-dialysis CKD
      children and 23 age-matched controls were enrolled in the study. The
      concentrations of analyzed parameters were assessed by ELISA. RESULTS: Serum and
      urine values of MMP-2, MMP-7, MMP-9, EMMPRIN and TGFbeta1 were significantly
      elevated in CKD patients versus controls. The MMP-2 and MMP-9 levels in urine
      correlated significantly with the corresponding values in serum, whereas MMP-7,
      EMMPRIN and TGFbeta1 urine concentrations did not. There were also significant
      correlations between urine values of all parameters. CONCLUSIONS: The increased
      urine levels of MMPs, EMMPRIN and TGFbeta1 indicate enhanced proteolysis and
      renal tissue remodeling. In the case of MMP-7, EMMPRIN and TGFbeta1 those
      disturbances seem independent of enhanced serum activity of the corresponding
      enzymes. The urine MMP-7 and EMMPRIN concentrations may serve as new independent
      indices of tissue remodeling and renal interstitial fibrosis in children with
      CKD.

PMID- 25945608
TI  - Catalytic water oxidation by a molecular ruthenium complex: unexpected generation
      of a single-site water oxidation catalyst.
AB  - The increasing energy demand calls for the development of sustainable energy
      conversion processes. Here, the splitting of H2O to O2 and H2, or related fuels,
      constitutes an excellent example of solar-to-fuel conversion schemes. The
      critical component in such schemes has proven to be the catalyst responsible for
      mediating the four-electron oxidation of H2O to O2. Herein, we report on the
      unexpected formation of a single-site Ru complex from a ligand envisioned to
      accommodate two metal centers. Surprising N-N bond cleavage of the designed
      dinuclear ligand during metal complexation resulted in a single-site Ru complex
      carrying a carboxylate-amide motif. This ligand lowered the redox potential of
      the Ru complex sufficiently to permit H2O oxidation to be carried out by the mild
      one-electron oxidant [Ru(bpy)3](3+) (bpy = 2,2'-bipyridine). The work thus
      highlights that strongly electron-donating ligands are important elements in the
      design of novel, efficient H2O oxidation catalysts. 

PMID- 25945607
TI  - Effect of triptolide on expression of thrombospondin-1 and transforming growth
      factor-beta1 in renal tubular cells.
AB  - The objective of our study is to investigate the effect of triptolide on
      expression of thrombospondin-1 and transforming growth factor beta1 in renal
      tubular cells. Human renal tubular epithelial cells were stimulated by different
      concentrations of triptolide (0.1, 1, and 10 MUg/L) in the presence of
      angiotensin-II (10(-7)mol/L). Real Time PCR was used to detect the mRNA
      expression of thrombospondin-1 and transforming growth factor beta1. Western blot
      analysis was used to detect the protein expression. ELISA was used to detect the
      level of total and active transforming growth factor beta1. The mRNA expression
      of thrombospondin-1 (3.66 +/- 0.48 vs. 1.33 +/- 0.26, p < 0.05) and transforming
      growth factor beta1 (3.58 +/- 0.59 vs. 1.26 +/- 0.28, p < 0.05) were up-regulated
      obviously when stimulated by angiotensin-II. And the protein expression of
      thrombospondin-1 (0.5126 +/- 0.0936 vs. 0.1025 +/- 0.0761, p < 0.01) and
      transforming growth factor beta1 (0.5948 +/- 0.0736 vs. 0.1318 +/- 0.0614, p <
      0.01) were also up-regulated simultaneously when stimulated by angiotensin-II.
      The expression of thrombospondin-1 and transforming growth factor beta1 induced
      by angiotensin-II were down-regulated markedly with 1 MUg/L and 10 MUg/L of
      triptolide in mRNA and protein levels (p < 0.05, p <  0.01). And triptolide (1
      and 10 MUg/L) could reduce the expression of total and active transforming growth
      factor beta1 (p < 0.05, p < 0.01). In conclusion, triptolide can inhibit the
      expression of thrombospondin-1 and transforming growth factor beta1 in mRNA and
      protein levels and down-regulate the levels of total and active transforming
      growth factor beta1.

PMID- 25945609
TI  - Photoluminescence Mechanism of DNA-Templated Silver Nanoclusters: Coupling
      between Surface Plasmon and Emitter and Sensing of Lysozyme.
AB  - DNA-templated silver nanoclusters (DNA-AgNCs) have now been thrust into the
      limelight with their superior optical properties and potential biological
      applications. However, the origin of photoluminescence from DNA-AgNCs still
      remains unclear. In this work, DNA-AgNCs were synthesized and the
      photoluminescence properties as well as the biosensing applications of the
      designed DNA-AgNCs were investigated. The photoluminescence properties of the DNA
      AgNCs were studied under three regions of excitation wavelength based on the UV
      visible absorption spectra. It was deemed that the photoluminescence originated
      from coupling between the surface plasmon and the emitter in AgNCs when they were
      excited by visible light above 500 nm, and thus the emission wavelength varied
      with changing the excitation wavelength. The photoluminescence of the red
      emitting-only AgNCs was the intrinsic fluorescence when excited from 200 to 400
      nm, which was only related to the emitter; but for two components of blue- and
      red-emitting AgNCs, the emission wavelength varied with the excitation wavelength
      ranging from 300 to 360 nm, and the photoluminescence was a coupling between the
      surface plasmon and the emitter. The photoluminescence was only related to the
      surface plasmon when the AgNCs were excited from 400 to 500 nm. Four DNA probes
      were designed and each contained two parts: one part was the template used to
      synthesize AgNCs and it was same to all, and the other part was the lysozyme
      binding DNA (LBD) used to bind lysozyme and two kinds of LBD were studied. It was
      deemed that the difference in DNA bases, sequence, and secondary structure caused
      the synthesized DNA-AgNCs to be different in photoluminescence properties and
      sensing ability to lysozyme, and the sensing mechanism based on photoluminescence
      enhancement was also presented. This work explored the origin of
      photoluminescence and the sensing ability of DNA-AgNCs, and is hoped to make a
      better understanding of this kind of photoluminescence probe. 

PMID- 25945610
TI  - Usability of assistive listening devices by older adults with low vision.
AB  - PURPOSE: This study examines the performance of individuals with both hearing and
      vision loss when using assistive listening devices. METHODS: Older adults (age 60
      100) with low vision only (n = 23), combined vision and hearing loss (n = 25) and
      a control group (n = 12) were asked to assemble a pocket talker, and operate a
      talking clock and an amplified telephone. They either received minimal or no
      instruction. Success at using the devices properly, as well as performance speed,
      was recorded. RESULTS: The proportion of individuals with sensory loss that was
      able to complete our naturalistic tasks without mistakes ranged from 20% to 95%,
      depending on the device, the task complexity and the instruction provided. Both
      instruction as well as simple repetition had statistically significant and
      separate beneficial effects; however, neither was able to bring success to 100%
      on any device. Speed and task success were linked in an intuitive way, whereby
      individuals who succeeded at a task also performed it faster. CONCLUSIONS: Even
      minimal explanation during the introduction of assistive listening devices to
      persons with low vision facilitates user success. Device visibility, cognitive
      and motor complexity of the task, as well as manual dexterity warrant further
      investigation as potential barriers to device use. Implications for
      Rehabilitation Hearing rehabilitation with individuals affected by vision loss
      requires additional attention and time to accommodate challenges with visibility
      and task complexity. Even minimal rehabilitation interventions can improve
      success and speed of device use. Repetition (practice) and instruction (strategy)
      have independent beneficial effects on device use. Dexterity, visibility, hand
      eye-coordination, task complexity and cognitive ability need to be considered
      when assigning assistive devices for older adults with vision and/or hearing
      loss.

PMID- 25945611
TI  - Cell cycle specific distribution of killin: evidence for negative regulation of
      both DNA and RNA synthesis.
AB  - p53 tumor-suppressor gene is a master transcription factor which controls cell
      cycle progression and apoptosis. killin was discovered as one of the p53 target
      genes implicated in S-phase control coupled to cell death. Due to its extreme
      proximity to pten tumor-suppressor gene on human chromosome 10, changes in
      epigenetic modification of killin have also been linked to Cowden syndrome as
      well as other human cancers. Previous studies revealed that Killin is a high
      affinity DNA-binding protein with preference to single-stranded DNA, and it
      inhibits DNA synthesis in vitro and in vivo. Here, co-localization studies of RFP
      Killin with either GFP-PCNA or endogenous single-stranded DNA binding protein RPA
      during S-phase show that Killin always adopts a mutually exclusive punctuated
      nuclear expression pattern with the 2 accessory proteins in DNA replication. In
      contrast, when cells are not in S-phase, RFP-Killin largely congregates in the
      nucleolus where rRNA transcription normally occurs. Both of these cell cycle
      specific localization patterns of RFP-Killin are stable under high salt
      condition, consistent with Killin being tightly associated with nucleic acids
      within cell nuclei. Together, these cell biological results provide a molecular
      basis for Killin in competitively inhibiting the formation of DNA replication
      forks during S-phase, as well as potentially negatively regulate RNA synthesis
      during other cell cycle phases. 

PMID- 25945612
TI  - ERG deletion is associated with CD2 and attenuates the negative impact of IKZF1
      deletion in childhood acute lymphoblastic leukemia.

PMID- 25945615
TI  - Effect of low salinity on the yellow clam Mesodesma mactroides.
AB  - The aim of this study was to determine the lethal salinity (LC50) for the yellow
      clam Mesodesma mactroides (Bivalvia: Mesodesmatidae) and identify
      histopathological alterations that could be used to diagnose structural changes
      in clam tissue. Clams in two size classes (adults and juveniles) were placed in
      10 L chambers and exposed to salinities of 35, 30, 25, 20, 15, 10, and 5 g/L.
      There were triplicate chambers with seven clams each for each salinity. The LC50
      values for a 48 h exposure were 6.5 g/L and 5.7 g/L for adults and juveniles,
      respectively. For a 96 h exposure, the LC50 values were 10.5 g/L for adults and
      8.8 g/L for juveniles. The histological examination of yellow clams exposed to 10
      g/L for 96 h showed intercellular oedema and necrotic foci in the epithelium of
      the digestive gland and occlusion of the lumen of the digestive gland. In
      conclusion, M. mactroides can be characterised as a moderately euryhaline
      species, tolerating salinities from 35 to 15 g/L. 

PMID- 25945614
TI  - Distribution of oligochaetes in a stream in the Atlantic Forest in southeastern
      Brazil.
AB  - The oligochaetes are considered good indicators of ecological conditions and
      specific types of habitats. Among the factors that influence the distribution of
      these invertebrates are the water flow and the nature of the substrate. The aim
      of this study is to describe the composition and distribution of oligochaete
      species in a first-order stream in Atlantic Forest and try to identify if some
      species are associated with characteristics of particular types of habitats. In
      the dry season and in the rainy season, sand and litter samples in two riffle
      areas and two pool areas were collected in different parts along the stream using
      a hand net. The greatest observed richness and abundance occurred in sand in the
      pool, however the greatest estimated richness was obtained for litter in the
      pool. The Kruskal-Wallis analysis showed effect of the different types of habitat
      on the abundance and richness of oligochaetes. The Nonmetric Multidimensional
      Scaling (NMDS) and Multiresponse Permutation Procedure analysis (MRPP) indicated
      that the variation in the fauna composition had relation with different types of
      substrates. The indicator species analysis showed that Limnodrilus. hoffmeisteri
      was an indicator species in both the riffle sand and pool sand and Pristina
      americana was only an indicator in the pool sand. The high organic matter content
      in both sandy habitats probably favored the greater abundance of oligochaetes.
      The results showed that the substrate constitutes an important factor for the
      local distribution of these invertebrates in streams. The variation of the
      community structure among mesohabitats and the presence of indicator species of
      specific types of habitats in the stream demonstrate the importance of
      environmental heterogeneity for the oligochaetes fauna in forested streams. 

PMID- 25945616
TI  - Living in a same microhabitat should means eating the same food? Diet and trophic
      niche of sympatric leaf-litter frogs Ischnocnema henselii and Adenomera marmorata
      in a forest of Southern Brazil.
AB  - In this study we analyzed diet composition, niche breadth and overlap of the two
      leaf-litter frogs Ischnocnema henselii and Adenomera marmorata. Frogs were
      collected in an Atlantic Rainforest area in the Reserva Natural Salto Morato, in
      Parana State, Southern Brazil, using plots of 16 m2 established on forest floor.
      Ischnocnema henselii consumed 18 different types of prey and the diet of this
      species was composed predominantly by Hymenoptera (Formicidae) (15.4%), Araneae
      (13.83%), Orthoptera (6.15%) and Opiliones (6.15%), whereas Adenomera marmorata
      consumed 15 different types of prey and its diet was composed mainly by
      Hymenoptera (Formicidae) (45.7%), Acari (31.8%) and Blattodea (14.8%). The niche
      breadth of I. henselii was BA = 0.43 and that of A. marmorata was BA = 0.19. The
      diet of the two sympatric species of leaf-litter frogs was basically composed by
      arthropods and the trophic niche overlap among them did not differ from expected
      at random. The differences in prey consumption should potentially facilitate the
      coexistence of two sympatric frogs on the forest floor. Possibly, this difference
      of prey consumption partly reflects differences in jaw width, species-specific
      body size of the two species and the period of activity of these two species. 

PMID- 25945613
TI  - Critical role of CAV1/caveolin-1 in cell stress responses in human breast cancer
      cells via modulation of lysosomal function and autophagy.
AB  - CAV1 (caveolin 1, caveolae protein, 22kDa) is well known as a principal
      scaffolding protein of caveolae, a specialized plasma membrane structure.
      Relatively, the caveolae-independent function of CAV1 is less studied. Autophagy
      is a process known to involve various membrane structures, including
      autophagosomes, lysosomes, and autolysosomes for degradation of intracellular
      proteins and organelles. Currently, the function of CAV1 in autophagy remains
      largely elusive. In this study, we demonstrate for the first time that CAV1
      deficiency promotes both basal and inducible autophagy. Interestingly, the
      promoting effect was found mainly in the late stage of autophagy via enhancing
      lysosomal function and autophagosome-lysosome fusion. Notably, the regulatory
      function of CAV1 in lysosome and autophagy was found to be caveolae-independent,
      and acts through lipid rafts. Furthermore, the elevated autophagy level induced
      by CAV1 deficiency serves as a cell survival mechanism under starvation.
      Importantly, downregulation of CAV1 and enhanced autophagy level were observed in
      human breast cancer cells and tissues. Taken together, our data reveal a novel
      function of CAV1 and lipid rafts in breast cancer development via modulation of
      lysosomal function and autophagy. 

PMID- 25945617
TI  - Short-term thermal stratification and partial overturning events in a warm
      polymictic reservoir: effects on distribution of phytoplankton community.
AB  - In lentic freshwater ecosystems, patterns of thermal stratification play a
      considerable part in determining the population dynamics of phytoplankton. In
      this study we investigated how these thermal patterns and the associated
      hydrodynamic processes affect the vertical distribution of phytoplankton during
      two consecutive diel cycles in a warm polymictic urban reservoir in the
      metropolitan region of Sao Paulo, Brazil. Water samples were taken and physical,
      chemical and biological data collected at half-meter intervals of depth along a
      water column at a fixed site, every 3 hours throughout the 48-hour period. Two
      events of stratification, followed by deepening of the thermocline occurred
      during the study period and led to changes in the vertical distribution of
      phytoplankton populations. Aphanocapsa delicatissima Nageli was the single
      dominant species throughout the 48-hour period. In the second diel cycle, the
      density gradient induced by temperature differences avoided the sedimentation of
      Mougeotia sp. C. Agardh to the deepest layers. On the other hand, Pseudanabaena
      galeata Bocher remained in the 4.0-5.5 m deep layer. The thermal structure of the
      water was directly affected by two meteorological factors: air temperature and
      wind speed. Changes in the cell density and vertical distribution of the
      phytoplankton were controlled by the thermal and hydrodynamic events. 

PMID- 25945618
TI  - Reproductive ecology of coypu (Myocastor coypus Molina, 1782) in the Middle Delta
      of the Parana River, Argentina.
AB  - The objective of this study was to estimate and compare some important
      reproductive parameters of Myocastor coypus over time (June 2006-May 2008), in
      wetlands of the Middle Delta of the Parana River (MD) Entre Rios province, R.
      Argentina. Within the original coypu distribution range, the MD is among the
      areas of highest habitat suitability for the species. Coypus were captured and
      the following reproductive parameters were estimated on a monthly, seasonal and
      annual basis: pregnancy rate (PR), litter size (LS), gross productivity (GP) and
      annual production (AP). Statistical non-parametric tests were used for
      comparisons. Additionally, the expected birth date of each embryo and fetus was
      estimated by assigning it to a developmental stage category and considering the
      gestation period of the species. All the parameters showed high values and PR and
      LS differed significantly between the dry (2006) and humid years (2007). Two
      peaks of birth were detected, one in spring and another one in mid-autumn. The
      implications of these results for ensuring the sustainable management of this
      rodent are discussed. 

PMID- 25945620
TI  - Chaco Chachalaca (Ortalis canicollis, Wagler, 1830) feeding ecology in a gallery
      forest in the South Pantanal (Brazil).
AB  - Cracids are generalist frugivores, which often exploit plant food resources such
      as flowers and leaves, mainly when fruit production declines. The Chaco
      chachalaca (Ortalis canicollis) is the most abundant cracid in the Pantanal
      (Brazil), and particularly common in the gallery forests. However, the factors
      related to their occurrence in this habitat type are unclear. In this study I
      describe the feeding habits and feeding niche breadth fluctuations of the Chaco
      chachalaca in relation to food resources abundance and diversity at the Miranda
      river gallery forest (Southern Pantanal). I also analyzed the relationships
      between Chaco chachalacas feeding activity and food resources abundance. This
      parameter (flowers and fruits) exhibited significant seasonal differences of
      abundance in which flowers were plentiful at the end of the dry, while fruits
      were abundant during the early wet season. However, food resources diversity to
      Chaco chachalacas exhibited no seasonal difference. Their feeding activity
      paralleled the availability of food resources, so that when some items were
      massively available an enhanced number of Chaco chachalacas foraged in the
      gallery forest, particularly during the prolonged dry season when they
      extensively used flowers and Genipa americana fruits. In fact, the Chaco
      chachalaca feeding niche breadth value presented low values in this period, while
      high values were common in the rest of the year. The flexible diet of this
      cracid, potentially favors their year round presence in the gallery forest,
      mainly during the prolonged dry season when the propensity for famine might be
      high. Since the Chaco chachalaca is among the largest and most abundant canopy
      frugivores in the gallery forest, it may contribute to forest regeneration, an
      underscored role due to the impact of annual floods and meandering dynamics on
      tree loss. 

PMID- 25945619
TI  - Floral resources and habitat affect the composition of hummingbirds at the local
      scale in tropical mountaintops.
AB  - Hummingbird communities tend to respond to variation in resources, having a
      positive relationship between abundance and diversity of food resources and the
      abundance and/or diversity of hummingbirds. Here we examined the influence of
      floral resource availability, as well as seasonality and type of habitat on the
      composition of hummingbird species. The study was carried out in two habitats of
      eastern Brazilian mountaintops. A gradient representative of the structure of
      hummingbird community, based on species composition, was obtained by the
      ordination of samples using the method of non-metric multidimensional scaling.
      The composition of hummingbird species was influenced by the type of habitat and
      floral resource availability, but not by seasonality. Hummingbird communities
      differ between habitats mainly due to the relative abundance of hummingbird
      species. The variation in composition of hummingbird species with the variation
      in floral resource availability may be related to differences in feeding habits
      of hummingbirds. Hummingbird species with the longest bills visited higher
      proportions of ornithophilous species, while hummingbirds with shorter bills
      visited higher proportions of non-ornithophilous species. The results demonstrate
      that at local-scale the composition of hummingbird species is affected by the
      type of habitat and floral resources availability, but not by seasonality. 

PMID- 25945621
TI  - Evidences that human disturbance simplify the ant fauna associated a
      Stachytarpheta glabra Cham. (Verbenaceae) compromising the benefits of ant-plant
      mutualism.
AB  - Interaction among species, like ants and plants through extrafloral nectaries
      (EFNs), are important components of ecological communities' evolution. However,
      the effect of human disturbance on such specific interactions and its ecological
      consequences is poorly understood. This study evaluated the outcomes of mutualism
      between ants and the EFN-bearing plant Stachytarpheta glabra under anthropogenic
      disturbance. We compared the arthropod fauna composition between two groups of
      twenty plant individuals, one in an area disturbed by human activities and one in
      a preserved area. We also check the plant investment in herbivory defense and the
      consequential leaf damage by herbivore. Our results indicate that such
      disturbances cause simplification of the associated fauna and lack of proper ant
      mutualist. This led to four times more herbivory on plants of disturbed areas,
      despite the equal amount of EFN and ant visitors and low abundance of herbivores.
      The high pressure of herbivory may difficult the re-establishment of S. glabra,
      an important pioneer species in ferruginous fields, therefore it may affect
      resilience of this fragile ecological community. 

PMID- 25945622
TI  - Phenolic compounds of Hibiscus sabdariffa and influence of organic residues on
      its antioxidant and antitumoral properties.
AB  - The aim of this study was to evaluate the phenolic and flavonoids contents and
      the antioxidant and antitumoral activity of leaf and calyx methanolic extracts
      from Hibiscus sabdariffa (roselle) cultivated with poultry litter and
      organosuper(r) under three modes of application. The total phenolic content in
      the each extract was determined using the Folin-Ciocalteu reagent and for
      aluminium chloride flavonoids. The antioxidant parameters were analyzed using a
      2, 2-diphenyl-1-picrylhydrazyl (DPPH.) free radical scavenging assay. An
      antitumor colorimetric assay using sulforhodamine B. The highest contents of
      phenolic and flavonoids were observed in leaf extracts (389.98 and 104.52 mg g-1,
      respectively) and calyx extracts (474.09 and 148.35 mg g-1, respectively) from
      plants cultivated with organosuper(r), although these values did not differ
      significantly from those observed for the other treatments. The average IC50 of
      leaves (43.48 MUg mL-1) and calyces (37.15 MUg mL-1) demonstrated that both have
      substances that may contribute to free radical scavenging action. The methanol
      extract from calyces showed significant selective activity against a leukemia
      line (K-562), with IC50 values of 0.12 mg mL-1 (organosuper(r)) and 1.16 mg mL-1
      (poultry litter), with concentration-dependent, cytotoxic and cytocidal effects. 

PMID- 25945623
TI  - Vegetative and reproductive phenology of Butia purpurascens Glassman (Arecaceae)
      under the effects of leaf harvesting.
AB  - Butia purpurascens is an endemic and threatened palm tree species that occurs in
      open areas of the Brazilian Cerrado, predominantly in southwestern Goias. The
      leaves of this palm tree are harvested by local people to fabricate brooms. This
      study evaluated changes in vegetative and reproductive phenology in two different
      natural populations of this palm tree: one population with leaf harvesting and
      another non-harvested population. Twenty plants were monitored in each area for
      23 months. The phenophases were related to the temperature and precipitation
      averages for a 30-year period. Leaf sprouting occurred throughout the year, with
      a slight reduction in periods of low temperatures and low rainfall. The first
      spathes emerged in March and flowering began during the dry season (June),
      continuing until January of the following year, concurrent with the period of
      most intense fruiting. Flowering and fruiting appear to be triggered by periods
      of drought, which are commonly observed in the Cerrado. The harvested sites
      produced significantly fewer leaves, spathes, inflorescences and infructescences
      than the non-harvested sites. Thus, the supply of resources to the local fauna is
      possibly reduced in sites under leaf exploitation, which in the long term can
      represent damage to the palm tree population's structure and dynamics. Other
      socioeconomic and ecological studies about the effects of leaf harvesting in B.
      purpurascens are necessary to enable strategies for sustainable use, devise
      management alternatives and conserve this threatened palm species. 

PMID- 25945625
TI  - Translocation and radio-telemetry monitoring of pygmy marmoset, Cebuella pygmaea
      (Spix, 1823), in the Brazilian Amazon.
AB  - Two groups of pygmy marmoset (Cebuella pygmaea) were rescued along the left bank
      of the Madeira River during the formation of Santo Antonio Hydroelectric Dam
      reservoir in the state of Rondonia, Northern Brazil. Reintroduction of both
      groups occurred in areas of open Tropical rainforest located within the project's
      Permanent Preservation Area. A post-release monitoring was conducted for three
      months using radio-telemetry. Individuals of each group remained together and
      settled in stable home ranges near their respective release sites. The mortality
      rate of translocated animals was about 7%. This seems to be the first report
      documenting the complete group translocation of C. pygmaea and the first to
      successfully employ radio-telemetry techniques in monitoring this species. This
      study demonstrated the feasibility of translocation and the use of radio
      telemetry in monitoring C. pygmaea. 

PMID- 25945624
TI  - Dero (Allodero) lutzi Michaelsen, 1926 (Oligochaeta: Naididae) associated with
      Scinax fuscovarius (Lutz, 1925) (Anura: Hylidae) from Semi-deciduous Atlantic
      Rain Forest, southern Brazil.
AB  - Amphibians are hosts for a wide variety of ecto- and endoparasites, such as
      protozoans and parasitic worms. Naididae is a family of Oligochaeta whose species
      live on a wide range of substrates, including mollusks, aquatic macrophytes,
      sponges, mosses, liverworts, and filamentous algae. However, some species are
      known as endoparasitic from vertebrates, such as Dero (Allodero) lutzi, which is
      parasitic of the urinary tracts of frogs, but also have a free-living stage.
      Specimens in the parasitic stage lack dorsal setae, branchial fossa, and gills.
      Here we report the occurrence of D. (A.) lutzi associated with anuran Scinax
      fuscovarius from Semi-deciduous Atlantic Rain Forest in southern Brazil. The
      study took place at the Caiua Ecological Station, Diamante do Norte, Parana,
      southern Brazil. Seven specimens of S. fuscovarius were examined for parasites
      but only one was infected. Parasites occurred in ureters and urinary bladder.
      Previous records of this D. (A.) lutzi include the Brazilian States of Santa
      Catarina, Sao Paulo, Rio de Janeiro, and Minas Gerais, as well as Cuba and North
      America. This is a new locality record for this species in Brazil. Reports of
      Dero (Allodero) lutzi are rare, due to difficulty of observation, and such events
      are restricted only the fortuitous cases. It is important to emphasize the
      necessity of future studies, which are fundamental to the understanding of
      biological and ecological aspects of this species. 

PMID- 25945626
TI  - First record of Ceratium furcoides (Dinophyta), an invasive species, in a
      temporary high-altitude lake in the Iron Quadrangle (MG, Southeast Brazil).
AB  - Dinoflagellates of the genus Ceratium are generally marine organisms, but rare
      occurrences in freshwater have been observed in Brazil. In this paper we are
      recording for the first time the presence of Ceratium furcoides, an invasive
      species, in a shallow, natural intermittent pool formed at a high-altitude at the
      southern end of the Iron Quadrangle, an iron-mining district of Minas Gerais
      State (Southeast Brazil). Samples were collected in October and November of 2010
      (rainy period). The population density of this organism observed in Lagoa Seca
      ("Dry Pool") was very low, at most 4 ind L-1. Mountain lakes are extremely
      vulnerable to atmospheric deposition of organisms, making them valuable witnesses
      both of the many forms of impact arising from human activities and of the
      extended global connections that facilitate the dispersion and introduction of
      new species over great distances. Studies on the population dynamics of C.
      furcoides in natural tropical systems are still rare and very recent to the
      brazilian scenario and hence the monitoring of its dynamics and the potential
      impact on aquatic communities of its becoming established are essential to an
      understanding of the process of bioinvasion by this species. 

PMID- 25945627
TI  - Distribution, management and diversity of the endangered Amerindian yam
      (Dioscorea trifida L.).
AB  - The objective of this study was to verify the occurrence of Dioscorea trifida in
      Brazil and to obtain information concerning its distribution, management and
      diversity. Farmers from 21 communities were interviewed in the states of Sao
      Paulo, Santa Catarina and Mato Grosso. During the visits, semi-structured
      interviews were conducted to collect socio-economic, management and diversity
      data for this crop. Fifty-one collected accessions, plus two accessions obtained
      at local markets of Amazonas, were characterized using 12 morphological traits.
      Most the interviewed farmers were men (75%) with a mean age of 59.5 years. Just a
      few young people and labor force were available for agricultural activities, with
      an average of only three individuals per farm. Most farmers (56%) grew only one
      variety of D. trifida, although 44% had more than one variety in their fields,
      which aims to provide greater assurance at harvest. Many popular names were
      observed for D. trifida, and cara roxo (purple yam) was the name most used by
      farmers (43.4%). Characters referring to the tuber, such as skin and flesh color,
      were most relevant for the distinction of the accessions. The results of this
      study may collaborate to develop strategies for conservation, both ex situ and in
      situ, within the view of on farm conservation. 

PMID- 25945628
TI  - Effect of fire on a monodominant floating mat of Cyperus giganteus Vahl in a
      neotropical wetland.
AB  - The rhizomatous Cyperus giganteus, abundant in the Pantanal wetland, can dominate
      extense floodable areas as monodominant communities. The Jacadigo lake has a
      large area of C. giganteus, where we performed an evaluation on community
      structure during two months in 2010, before it was hit by a wildfire which top
      killed the vegetation, compared to ten months post-fire. We utilized 40 plots of
      1m * 1m, along permanent trails, assessing two strata: the upper, near the
      inflorescence of adult plants, and the lower, close to the water level. Our
      results show that fire does not affect dominance of C. giganteus, as it
      maintained the same cover as before fire; species richness is not much altered
      either - 28 before fire and 34 thereafter. Fire changed the floristic
      composition, due to the annual variation of species and the ability of some
      plants to colonize gaps and to regrow after fire from underground organs and
      seeds. The stratification of the vegetation with characteristic species of upper
      and lower strata was similar after fire. 

PMID- 25945629
TI  - Alterations in land uses based on amendments to the Brazilian Forest Law and
      their influences on water quality of a watershed.
AB  - The amendments to the Forest Law proposed by the Brazilian government that allow
      partial substitution of forested areas by agricultural activities raised deep
      concern about the integrity of aquatic ecosystems. To assess the impacts of this
      alteration in land uses on the watershed, diffuse loads of total nitrogen (Nt)
      and total phosphorus (Pt) were estimated in Lobo Stream watershed, southeastern
      Brazil, based on export coefficients of the Model of Correlation between Land Use
      and Water Quality (MQUAL). Three scenarios were generated: scenario 1 (present
      scenario), with 30-meter-wide permanent preservation areas along the shore of
      water bodies and 50-meter-radius in springs; scenario 2, conservative, with 100
      meter-wide permanent preservation areas along water bodies; and scenario 3, with
      the substitution of 20% of natural forest by agricultural activities. Results
      indicate that a suppression of 20% of forest cover would cause an increase in
      nutrient loads as well as in the trophic state of aquatic ecosystems of the
      watershed. This could result in losses of ecosystem services and compromise the
      quality of water and its supply for the basin. This study underlines the
      importance of forest cover for the maintenance of water quality in Lobo Stream
      watershed. 

PMID- 25945630
TI  - How the fluctuations of water levels affect populations of invasive bivalve
      Corbicula fluminea (Muller, 1774) in a Neotropical reservoir?
AB  - Corbicula fluminea is an invasive bivalve responsible for several environmental
      and financial problems around the globe. Despite the invasive potential of this
      species, it suffers certain restrictions in lentic environments due to natural
      phenomena that significantly affect its population structure (e.g. water column
      fluctuation and sunlight exposure). The present study addresses how temporal
      decline of the water level in a Neotropical reservoir and exposure to sunlight
      affect the population structure of C. fluminea. Samplings were carried out twice
      in the reservoir of Furnas Hydroelectric Power Station (HPS) (Minas Gerais,
      Brazil), in 2011 and 2012. Population density, spatial distribution and mean
      shell length of C. fluminea were estimated for each year after sampling in 51
      quadrats (0.0625m2) placed on three transects at different distances along the
      reservoir margins (0, 10 and 20 m from a fixed-point). We observed a predominance
      of C. fluminea in both years, with a simultaneous gradual decrease in density and
      richness of native species in the sampling area. Significant differences in
      density of C. fluminea were registered at different distances from the margin,
      and are related to the temporal variability of physical conditions of the
      sediment and water in these environments. We also registered a trend toward an
      increase in the density and aggregation of C. fluminea as we moved away from the
      margin, due to the greater stability of these areas (>10 m). The mean shell
      length of C. fluminea showed significant difference between the distinct
      distances from the margin and during the years, as well as the interaction of
      these factors (Distances vs.Years). These results were associated with the
      reproductive and invasive capacity of this species. This study reveals that these
      temporal events (especially water column fluctuation) may cause alterations in
      density, spatial distribution and mean shell length of C. fluminea and the
      composition of the native malacofauna in Neotropical lentic environments. 

PMID- 25945631
TI  - The rainy season increases the abundance and richness of the aquatic insect
      community in a Neotropical reservoir.
AB  - Alterations in aquatic systems and changes in water levels, whether due to rains
      or dam-mediated control can cause changes in community structure, forcing the
      community to readjust to the new environment. This study tested the hypothesis
      that there is an increase in the richness and abundance of aquatic insects during
      the rainy season in the Serra da Mesa Reservoir, with the premise that increasing
      the reservoir level provides greater external material input and habitat
      diversity, and, therefore, conditions that promote colonization by more species.
      We used the paired t test to test the differences in richness, beta diversity,
      and abundance, and a Non-metric Multidimensional Scaling (NMDS) was performed to
      identify patterns in the community under study. Additionally, Pearson
      correlations were analyzed between the richness, abundance, and beta diversity
      and the level of the reservoir. We collected 35,028 aquatic insect larvae (9,513
      in dry period and 25,515 in the rainy season), predominantly of the Chironomidae
      family, followed by orders Ephemeroptera, Trichoptera, and Odonata. Among the 33
      families collected, only 12 occurred in the dry season, while all occurred in the
      rainy season. These families are common in lentic environments, and the dominance
      of Chironomidae was associated with its fast colonization, their behavior of
      living at high densities and the great tolerance to low levels of oxygen in the
      environment. The hypothesis was confirmed, as the richness, beta diversity, and
      abundance were positively affected by the increase in water levels due to the
      rainy season, which most likely led to greater external material input, greater
      heterogeneity of habitat, and better conditions for colonization by several
      families. 

PMID- 25945632
TI  - Non-destructive linear model for leaf area estimation in Vernonia ferruginea
      Less.
AB  - Leaf area estimation is an important biometrical trait for evaluating leaf
      development and plant growth in field and pot experiments. We developed a non
      destructive model to estimate the leaf area (LA) of Vernonia ferruginea using the
      length (L) and width (W) leaf dimensions. Different combinations of linear
      equations were obtained from L, L2, W, W2, LW and L2W2. The linear regressions
      using the product of LW dimensions were more efficient to estimate the LA of V.
      ferruginea than models based on a single dimension (L, W, L2 or W2). Therefore,
      the linear regression "LA=0.463+0.676WL" provided the most accurate estimate of
      V. ferruginea leaf area. Validation of the selected model showed that the
      correlation between real measured leaf area and estimated leaf area was very
      high. 

PMID- 25945633
TI  - Fish stomach contents in benthic macroinvertebrate assemblage assessments.
AB  - The choice of sampling gears to assess benthic macroinvertebrate communities
      depends on environmental characteristics, study objectives, and cost
      effectiveness. Because of the high foraging capacity and diverse habitats and
      behaviors of benthophagous fishes, their stomach contents may offer a useful
      sampling tool in studies of benthic macroinvertebrates, especially in large,
      deep, fast rivers that are difficult to sample with traditional sediment sampling
      gear. Our objective was to compare the benthic macroinvertebrate communities
      sampled from sediments with those sampled from fish stomachs. We collected
      benthic macroinvertebrates and fish from three different habitat types
      (backwater, beach, riffle) in the wet season, drying season, and dry season along
      a single reach of the Grande River (Parana River Basin, southeast Brazil). We
      sampled sediments through use of a Petersen dredge (total of 216 grabs) and used
      gill nets to sample fish (total of 36 samples). We analyzed the stomach contents
      of three commonly occurring benthophagous fish species (Eigenmannia virescens,
      Iheringichthys labrosus, Leporinus amblyrhynchus). Chironomids dominated in both
      sampling methods. Macroinvertebrate taxonomic composition and abundances from
      fish stomachs differed from those from sediment samples, but less so from riffles
      than from backwater and beach habitats. Macroinvertebrate taxa from E. virescens
      stomachs were more strongly correlated with sediment samples from all three
      habitats than were those from the other two species. The species accumulation
      curves and higher mean dispersion values, compared with with sediment samples
      suggest that E. virescens is more efficient than sediment samples and the other
      fish studied at collecting benthic taxa. We conclude that by analyzing the
      stomach contents of benthophagous fishes it is possible to assess important
      characteristics of benthic communities (dispersion, taxonomic composition and
      diversity). This is especially true for studies that only sample fish assemblages
      to evaluate aquatic ecosystem impacts. Therefore, this approach can be useful to
      amplify assessments of human impacts, and to incorporate additional
      bioindicators. 

PMID- 25945634
TI  - Cyanobacteria bloom: selective filter for zooplankton?
AB  - The Ibirite reservoir is an urban and eutrophic environment, with regular
      occurrences of cyanobacteria blooms. The reservoir is warm monomict and remains
      stratified most of the year, circulating in the dry season (winter). During the
      hydrological cycle of October/07 to October/08 there were four scenarios with
      different environmental conditions, which influenced the structure of the
      zooplankton community, as confirmed in a previous study. Changes in the
      zooplankton community structure between the scenarios were studied, aiming at
      analyzing the stability and persistence of this community. The Spearman's
      coefficient of correlation was used to measure the stability; the persistence was
      evaluated through a cluster analysis and changes in community composition were
      estimated by the "temporal" beta diversity index. Considering the distribution
      patterns of abundance, the community was stable only in the transition between
      scenarios 1 and 2 (n = 30, r = 0.71, p = 0.00001), when there were no
      cyanobacteria blooms. The persistence of zooplankton between the scenarios was
      low, showing a distinct species composition for each scenario. The highest
      variations in species composition, observed by the values of temporal beta
      diversity index, were the transitions between scenarios 3-0 (1.45) and 0-1
      (1.05), and the lowest variations occurred in the transition between scenarios 1
      2 (0.57). The results suggest that the cyanobacteria blooms at Ibirite reservoir
      are be acting as "selective filters", and are, thus, disturbances with sufficient
      ability to change the structure of the zooplankton community.

PMID- 25945635
TI  - A new species of gall midge associated with Diplopterys pubipetala (A.Juss.)
      Anderson and Davis (Malpighiaceae) from Altinopolis, Sao Paulo, Brazil.
AB  - Clinodiplosis bellum sp. nov. associated with Diplopterys pubipetala (A.Juss.)
      Anderson and Davis (Malpighiaceae) from Brazil are described. This is the first
      species of Clinodiplosis described to State of Sao Paulo and the first formal
      description of Diplopterys pubipetala (Malpighiaceae) as host plant of
      Cecidomyiidae species. Description and illustration of the Clinodiplosis bellum
      sp. nov. (Diptera: Cecidomyiidae) are given. 

PMID- 25945636
TI  - Biomass of macroinvertebrates and physicochemical characteristics of water in an
      Andean urban wetland of Colombia.
AB  - Aquatic macroinvertebrates (AMI) play an important role in the ecology of
      wetlands, either by their job as regulators of the cycles of matter, as for their
      energy storage function represented in their biomass, which is transferred to
      higher trophic levels. To answer the question of how biomass of different AMI
      trophic guilds is related with physicochemical variables in the wetland Jaboque
      (Bogota, Colombia), four samplings were achieved between April 2009 and January
      2010, according to periods of rain and drought in the region. The AMI biomass
      values obtained were rated as of intermediate rank. No temporal but spatial
      significant differences were found. Apparently these spatial differences appear
      to be associated with variations in anthropogenic pressure, which differs in each
      area of the wetland. In dry months (January and August), biomass was greater and
      dominated by detritivores. We observed a positive relationship between the
      specific conductance of water and the biomass of predators and detritivores and
      between water temperature and the biomass of detritivores and shredders. These
      relationships suggest that the physical and chemical variables influence the
      distribution, abundance, and biomass of functional groups. The physical and
      chemical conditions of water exhibited spatiotemporal fluctuations related to
      changes in the concentration of organic matter and nutrients, which presumably
      were related to the affluents discharges and the high impact of local human
      populations. 

PMID- 25945637
TI  - Striped-tailed Yellow-finch nesting success in abandoned mining pits from central
      Brazilian cerrado.
AB  - Suitability of degraded areas as breeding habitats can be tested through
      assessment of nest predation rates. In this study we estimated nest success in
      relation to several potential predictors of nest survival in the Stripe-tailed
      Yellow-finch (Sicalis citrina) breeding in abandoned mining pits at Brasilia
      National Park. We monitored 73 nests during the 2007-breeding season. Predation
      was the main cause of nest failure (n = 48, 66%); while six nests were abandoned
      (8%) and 19 nests produced young (26%). Mayfield's daily survival rates and nest
      success were 0.94 and 23%, respectively. Our results from nest survival models on
      program MARK indicated that daily survival rates increase linearly towards the
      end of the breeding season and decrease as nests aged. None of the nest
      individual covariates we tested - nest height, nest size, nest substrate, and
      edge effect - were important predictors of nest survival; however, nests placed
      on the most common plant tended to have higher survival probabilities. Also,
      there was no observer effect on daily survival rates. Our study suggests that
      abandoned mining pits may be suitable alternative breeding habitats for Striped
      tailed Yellow-finches since nest survival rates were similar to other studies in
      the central cerrado region.

PMID- 25945638
TI  - Reproductive aspects of the flyingfish, Hirundichthys affinis from the
      Northeastern coastal waters of Brazil.
AB  - The epipelagic flyingfish, Hirundichthys affinis is a major artisanal fishery
      resource from the Northeastern coastal waters of Brazil. However, biological
      information about this species has been poorly documented. This paper presents
      data on the length-weight relationship, sex ratio, length at first sexual
      maturity, gonadal development and fecundity of H. affinis sampled from the
      coastal waters of Rio Grande do Norte, Brazil. The total body length and weight
      for both sexes ranged from 23.4 to 29.4 cm and from 89 to 188g, respectively. The
      allometric coefficient of males was 2.208 and that of females was 2.985,
      indicating negatively allometric growth. The sex ratio was 1M:1.6F thus differing
      from the expected ratio of 1:1 (chi2 = 18.63). The total length at first sexual
      maturity was estimated at 27.3 cm for males and 27.1 cm for females. The
      macroscopic characteristics of the gonads indicated four maturation stages.
      Histological studies of gonads of H. affinis showed seven phases of oocyte
      development and four phases of spermatocyte development. The mean absolute
      fecundity was 9092 vitelogenic oocytes. Spawning occurred during the months of
      March to July. The microscopic descriptions of the stages of gonad maturation
      indicate that the study area is an important spawning ground of H. affinis. 

PMID- 25945639
TI  - About rats and jackfruit trees: modeling the carrying capacity of a Brazilian
      Atlantic Forest spiny-rat Trinomys dimidiatus (Gunther, 1877) - Rodentia,
      Echimyidae - population with varying jackfruit tree (Artocarpus heterophyllus L.)
      abundances.
AB  - We carried out a six-year study aimed at evaluating if and how a Brazilian
      Atlantic Forest small mammal community responded to the presence of the invasive
      exotic species Artocarpus heterophyllus, the jackfruit tree. In the surroundings
      of Vila Dois Rios, Ilha Grande, RJ, 18 grids were established, 10 where the
      jackfruit tree was present and eight were it was absent. Previous results
      indicated that the composition and abundance of this small mammal community were
      altered by the presence and density of A. heterophyllus. One observed effect was
      the increased population size of the spiny-rat Trinomys dimidiatus within the
      grids where the jackfruit trees were present. Therefore we decided to create a
      mathematical model for this species, based on the Verhulst-Pearl logistic
      equation. Our objectives were i) to calculate the carrying capacity K based on
      real data of the involved species and the environment; ii) propose and evaluate a
      mathematical model to estimate the population size of T. dimidiatus based on the
      monthly seed production of jackfruit tree, Artocarpus heterophyllus and iii)
      determinate the minimum jackfruit tree seed production to maintain at least two
      T. dimidiatus individuals in one study grid. Our results indicated that the
      predicted values by the model for the carrying capacity K were significantly
      correlated with real data. The best fit was found considering 20~35% energy
      transfer efficiency between trophic levels. Within the scope of assumed premises,
      our model showed itself to be an adequate simulator for Trinomys dimidiatus
      populations where the invasive jackfruit tree is present. 

PMID- 25945640
TI  - Brazilian scientific production on phytoplankton studies: national determinants
      and international comparisons.
AB  - In this study, we determined the temporal trends of publications by Brazilian
      authors on phytoplankton and compared these trends to those of other Latin
      American countries as well as to the 14 countries ranking ahead of Brazil in
      terms of scientific publication. To do this, we investigated phytoplankton
      studies published in an international database (Thomson-ISI). The data showed
      that Brazil plays an important role among other Latin American countries in the
      publication of these studies. Moreover, the trend of studies published on
      phytoplankton in Brazil was similar to trends recorded in the developed countries
      of the world. We conclude that studies can be more deliberately targeted to
      reduce national and international asymmetries by focusing on projects with large
      spatial scales and projects that concentrate on less-studied geographic regions,
      thus encouraging increased productivity in remote areas of the country.
      Associated with this is a necessary increase in high-impact journal publications,
      increasing the quantity and quality of Brazilian scientific studies on
      phytoplankton and, consequently, their global visibility. 

PMID- 25945641
TI  - DDRT-PCR approaches applied for preeminent results in the isolation of DETs from
      fish brain tissues.
AB  - Differential Display (DD) is a technique widely used in studies of differential
      expression. Most of these analyses, especially those involving fish species, are
      restricted to species from North America and Europe or to commercial species, as
      salmonids. Studies related to South American fish species are underexplored.
      Thus, the present work aimed to describe DD technique modifications in order to
      improve outcomes related to the isolation of DETs (Differentially Expressed
      Transcripts), using Leporinus macrocephalus, a large commercially exploited South
      American species, as a fish design. Different DDRT-PCR approaches were applied to
      brain samples and the products of the reactions were analyzed on 6%
      polyacrylamide gels stained with 0.17% Silver Nitrate (AgNO3). The use of PCR
      reactions under high stringency conditions and longer oligonucleotides based on
      VNTR (Variable Number of Tandem Repeats) core sequences led to better results
      when compared to low stringency PCR conditions and the use of decamer
      oligonucleotides. The improved approach led to the isolation of differentially
      expressed transcripts on adult males and females of L. macrocephalus. This study
      indicates that some modifications on the DDRT-PCR method can ensure isolation of
      DETs from different fish tissues and the development of robust data related to
      this approach. 

PMID- 25945642
TI  - First record of Palombitrema triangulum (Suriano, 1981) Suriano, 1997 (Monogenea:
      Dactylogyridae) from freshwater fishes in Brazil.
AB  - This study reports for the first time the monogenean Palombitrema triangulum
      Suriano (1981) in freshwater fishes from Brazil, highlighting new sites of
      infection for this helminth and some morphological differences. Monogeneans were
      collected on the body surface, gills and nasal cavity of two native fish species
      from Brazil, Cyphocharax modestus (Fernandez-Yepez, 1948) and Cyphocharax nagelii
      (Steindachner, 1881). A brief morphological characterization of this species is
      presented. 

PMID- 25945643
TI  - Priming and temperature limits for germination of dispersal units of Urochloa
      brizantha (Stapf) Webster cv. basilisk.
AB  - The objective of this study was to evaluate the effect of priming treatments on
      the upper and lower thermal limits for germination of Urochloa brizantha cv.
      basilisk, and testing the hypothesis that pre-imbibition affect thermal
      parameters of the germination. Pre-imbibed seeds both in distilled water (0 MPa)
      and PEG 6000 solution (-0.5 MPa) were put to germinate in different temperatures.
      It is suggested that U. brizantha seeds have low response to priming when they
      were placed to germinate in medium where water is not limiting. The response of
      U. brizantha seeds to priming is dependent on the temperature and water potential
      conditions at which the seeds are pre-imbibed, as well as on the germination
      temperature. The optimum temperature for germination of U. brizantha shift toward
      warmer temperatures in primed seeds. Priming effect was more pronounced at
      temperatures closer to the upper and lower limit for germination, but probably
      that response cannot be accounted for changes in the thermal time constant
      (thetaT(g)) and ceiling temperature (Tc(g)). Otherwise, a decrease in the base
      temperature (Tb) was observed in primed seeds, suggesting that the Tb
      distribution in U. brizantha seeds is influenced by priming. 

PMID- 25945644
TI  - Helminth fauna of Astyanax fasciatus Cuvier, 1819, in two distinct sites of the
      Taquari River, Sao Paulo State, Brazil.
AB  - This study assessed the helminth fauna of Astyanax fasciatus in two distinct
      sites of the Taquari River, Sao Paulo State, with 30 individuals sampled in a
      lotic site and 30 in a lentic site, recording the monogeneans: Cacatuocotyle
      paranaensis, Characithecium costaricensis, Diaphorocleidus kabatai, Jainus sp.,
      Notozothecium sp. and Gyrodactylus sp., the digenean Antorchis lintoni and no
      identified metacercariae; the nematode Procamallanus (Spirocamallanus) inopinatus
      and no-identified larvae. The mean abundances of total monogeneans (U = 1053; p =
      0.042) and C. costaricensis (U = 1107; p = 0.005) were higher in the lotic site.
      This difference may be due to the higher density of the host population in the
      lotic site, and the water transparence in lentic environments that prevents A.
      fasciatus to form shoals, precluding the exchange of parasites with direct cycle
      within a host population. This study is the first report of the helminth fauna of
      A. fasciatus in the Taquari River, with ten taxa recorded, and reports A.
      fasciatus as a new host for Notozothecium sp. and C. paranaensis. 

PMID- 25945645
TI  - Helminths of the frog Pleurodema diplolister (Anura, Leiuperidae) from the
      Caatingain Pernambuco State, Northeast Brazil.

PMID- 25945646
TI  - Migration rate and genetic diversity of two Drosophila maculifrons (Duda, 1927)
      populations from Highland Araucaria Forest Fragments in Southern Brazil.

PMID- 25945648
TI  - Erratum.

PMID- 25945647
TI  - Brazilian scientist is part of elite group of researchers fighting cancer,
      obtains an unprecedented patent in the United States.

PMID- 25945649
TI  - Global changes, cyanobacterial blooms and threats to aquatic biodiversity.

PMID- 25945650
TI  - Stabilization of the Simplest Criegee Intermediate from the Reaction between
      Ozone and Ethylene: A High-Level Quantum Chemical and Kinetic Analysis of
      Ozonolysis.
AB  - The fraction of the collisionally stabilized Criegee species CH2OO produced from
      the ozonolysis of ethylene is calculated using a two-dimensional (E, J)-grained
      master equation technique and semiclassical transition-state theory based on the
      potential energy surface obtained from high-accuracy quantum chemical
      calculations. Our calculated yield of 42 +/- 6% for the stabilized CH2OO agrees
      well, within experimental error, with available (indirect) experimental results.
      Inclusion of angular momentum in the master equation is found to play an
      essential role in bringing the theoretical results into agreement with the
      experiment. Additionally, yields of HO and HO2 radical products are predicted to
      be 13 +/- 6% and 17 +/- 6%, respectively. In the kinetic simulation, the HO
      radical product is produced mostly from the stepwise decomposition mechanism of
      primary ozonide rather than from dissociation of hot CH2OO. 

PMID- 25945651
TI  - Do we really need kidneys-ureters-bladder radiography to predict stone
      radiopacity before treatment with shockwave lithotripsy? Development and internal
      validation of a novel predictive model based on computed tomography parameters.
AB  - PURPOSE: To produce and validate a predictive model based on CT parameters for
      calculating the probability of a stone to be visible on fluoroscopy of shockwave
      lithotripsy (SWL) and to compare its accuracy to that of kidneys-ureters-bladder
      (KUB) radiography. METHODS: We retrospectively analyzed 306 patients (sample
      group) who underwent an SWL between March 2011 and August 2012. A multivariate
      analysis of several parameters extracted from the preoperative CT scan was
      conducted to identify independent predictors for radiopacity on SWL fluoroscopy.
      The results were used for the creation of a predictive model. Internal validation
      was made on a group of 75 patients (validation group) treated from September 2012
      until December 2012. Predictive accuracy of the model was evaluated by receiver
      operating characteristic (ROC) curve and calibration plot. The ROC curve was also
      used for comparing the predictive accuracy of the model to that of KUB
      radiography. RESULTS: From 306 evaluated stones, 238 (77.8%) were visible on
      fluoroscopy. Results of the multivariate analysis revealed that stone size
      (P<0.001), stone attenuation (P<0.001), location in the midureter (P<0.001), the
      distance between the stone and the anterior abdominal wall (P<0.001), and fat
      thickness of the anterior abdominal wall (P=0.001) were all independent
      predictors for stone radiopacity on fluoroscopy. A predictive model was produced
      based on the above parameters. The model demonstrated high calibration and areas
      under the curve of 0.923 and 0.965 in the sample and validation group,
      respectively, while its predictive performance was significantly higher (P<0.001)
      of that of KUB radiography (area under the curve=0.727). CONCLUSIONS: This novel
      model can estimate with high accuracy stone radiopacity on SWL fluoroscopy using
      parameters of CT scan and thus it can be used as an alternative to KUB
      radiography for treatment planning.

PMID- 25945653
TI  - Garlic consumption and colorectal cancer risk in man: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: Colorectal cancer shows large incidence variations worldwide that have
      been attributed to different dietary factors. We conducted a meta-analysis on the
      relationship between garlic consumption and colorectal cancer risk. DESIGN: We
      systematically reviewed publications obtained by searching ISI Web of Knowledge,
      MEDLINE and EMBASE literature databases. We extracted the risk estimate of the
      highest and the lowest reported categories of intake from each study and
      conducted meta-analysis using a random-effects model. RESULTS: The pooled
      analysis of all fourteen studies, seven cohort and seven case-control, indicated
      that garlic consumption was not associated with colorectal cancer risk (OR=0.93;
      95 % CI 0.82, 1.06, P=0.281; I 2=83.6 %, P<=0.001). Separate analyses on the
      basis of cancer sites and sex also revealed no statistically significant effects
      on cancer risk. However, when separately analysed on the basis of study type, we
      found that garlic was associated with an approximately 37 % reduction in
      colorectal cancer risk in the case-control studies (combined risk estimate=0.63,
      95 % CI 0.48, 0.82, P=0.001; I 2=75.6 %, P<=0.001). CONCLUSIONS: Our results
      suggest that consumption of garlic is not associated with a reduced colorectal
      cancer risk. Further investigations are necessary to clarify the discrepancy
      between results obtained from different types of epidemiological studies.

PMID- 25945654
TI  - Testing the Penrose Hypothesis-Reply.

PMID- 25945652
TI  - Modulation of insulin degrading enzyme activity and liver cell proliferation.
AB  - Diabetes mellitus type 2 (T2DM), insulin therapy, and hyperinsulinemia are
      independent risk factors of liver cancer. Recently, the use of a novel inhibitor
      of insulin degrading enzyme (IDE) was proposed as a new therapeutic strategy in
      T2DM. However, IDE inhibition might stimulate liver cell proliferation via
      increased intracellular insulin concentration. The aim of this study was to
      characterize effects of inhibition of IDE activity in HepG2 hepatoma cells and to
      analyze liver specific expression of IDE in subjects with T2DM. HepG2 cells were
      treated with 10 nM insulin for 24 h with or without inhibition of IDE activity
      using IDE RNAi, and cell transcriptome and proliferation rate were analyzed.
      Human liver samples (n = 22) were used for the gene expression profiling by
      microarrays. In HepG2 cells, IDE knockdown changed expression of genes involved
      in cell cycle and apoptosis pathways. Proliferation rate was lower in IDE
      knockdown cells than in controls. Microarray analysis revealed the decrease of
      hepatic IDE expression in subjects with T2DM accompanied by the downregulation of
      the p53-dependent genes FAS and CCNG2, but not by the upregulation of
      proliferation markers MKI67, MCM2 and PCNA. Similar results were found in the
      liver microarray dataset from GEO Profiles database. In conclusion, IDE
      expression is decreased in liver of subjects with T2DM which is accompanied by
      the dysregulation of p53 pathway. Prolonged use of IDE inhibitors for T2DM
      treatment should be carefully tested in animal studies regarding its potential
      effect on hepatic tumorigenesis. 

PMID- 25945655
TI  - Trauma Patients: Health Insurance Reform Is Only the Beginning.

PMID- 25945657
TI  - Reflections on a year of making a difference in aerospace medicine.

PMID- 25945658
TI  - Validation of a portable, touch-screen psychomotor vigilance test.
AB  - INTRODUCTION: The Psychomotor Vigilance Test (PVT) measures effects of fatigue
      from sleep loss and circadian misalignment on sustained vigilance performance. To
      promote PVT use in field environments, a 5-min PVT version has been implemented
      on a personal digital assistant (PDA) with a touch screen. The present laboratory
      study was conducted to validate this PVT against a standard 10-min laptop PVT
      across 38 h of total sleep deprivation (TSD). METHODS: Following a baseline sleep
      night, subjects underwent 38 h of TSD, during which they performed the PVT every
      hour, alternating between the two test platforms. The study concluded with a
      night of recovery sleep. RESULTS: The primary outcome was the number of PVT
      lapses (reaction times > 500 ms). Both PVT platforms showed significant effects
      for the number of lapses across TSD test times involving an increase with time
      awake modulated by circadian rhythm. Laptop PVT lapses across test times
      exhibited a large effect size (f2 = 0.36), whereas PDA PVT lapses exhibited a
      medium effect size (f2 = 0.17). The laptop PVT showed a significant effect for
      the number of false starts during TSD similar to the temporal profile of lapses,
      while the PDA PVT had false starts throughout the TSD period. DISCUSSION: The 5
      min PDA PVT provided performance testing functionality and results comparable to
      the 10-min laptop PVT. The number of PDA PVT lapses tracked fatigue similarly to
      the laptop PVT lapses, albeit with smaller average ranges and effect sizes.

PMID- 25945659
TI  - Human gait at sea while walking fore-aft vs. athwart.
AB  - BACKGROUND: Sea travel leads to well-known changes in gait, but these effects
      have not been evaluated using quantitative data obtained through controlled
      experiments. We obtained quantitative data on step-timing patterns as experienced
      maritime crewmembers walked on a ship at sea. METHODS: Using a within-subjects
      design, crewmembers walked back and forth along straight line paths (11 m long)
      that were parallel with the ship's long (i.e., fore-aft) and short (i.e.,
      athwart) axes. Using contact switches attached to the feet, we measured temporal
      parameters of gait, including stride time, the variability of stride time, and
      the coefficient of variation. We also evaluated the temporal dynamics of stride
      times using detrended fluctuation analysis. RESULTS: The variability of stride
      time differed between walking fore-aft (mean = 0.10 s) and walking athwart (mean
      = 0.28 s). The coefficient of variation also differed between walking fore-aft
      (mean = 11%) and walking athwart (mean = 43%). CONCLUSIONS: We obtained direct
      evidence that ship motions in roll and pitch differentially affect the timing of
      stepping patterns in human gait. This novel finding motivates new research on
      quantitative parameters of gait at sea.

PMID- 25945660
TI  - Visual blur and motion sickness in an optokinetic drum.
AB  - BACKGROUND: The most commonly cited hypotheses for motion sickness (MS) focus on
      inconsistent sensory inputs. Visual/vestibular conflicts may lead to MS, but
      visual input from retinal regions/neural pathways that are sensitive to motion
      might bear more weight in MS etiology. We hypothesized that inducing blurred
      vision in an optokinetic drum would attenuate the influence of foveal
      (parvocellular) input, but not peripheral (magnocellular) input that is sensitive
      to motion. Increased relative influence of peripheral visual input was predicted
      to subsequently lead to more visual/vestibular conflict and subsequently more
      severe MS symptoms. METHODS: Through goggles that were either clear or frosted,
      15 subjects (5 men, 10 women, mean age = 24.9 yr, range = 18-49) viewed the
      interior of a rotating (60 degrees  . s(-1)) optokinetic drum for 10 min.
      Subjects completed the Simulator Sickness Questionnaire (SSQ) before and after
      viewing. Overall subjective sickness ratings (0-10) and visually induced self
      motion perception (vection) ratings (0-10) were also recorded. RESULTS:
      Postexposure SSQ scores obtained in the blur condition (total - 52.9, oculomotor 
      38.9, disorientation - 69.6) were significantly higher than those obtained in
      the control condition (total - 30.4, oculomotor - 21.7, disorientation - 37.8).
      Overall sickness ratings and vection ratings were also significantly higher in
      the blur condition. CONCLUSIONS: These results suggest that visual blur can
      exacerbate MS, perhaps because of differential influences of visual pathways.
      Although these results were obtained with an optokinetic drum, possible effects
      of visual blurring in motion provocative environments such aircraft, watercraft,
      spacecraft, and land vehicles should be considered.

PMID- 25945661
TI  - Cross-sectional study of neck pain and cervical sagittal alignment in air force
      pilots.
AB  - BACKGROUND: There is a high prevalence of neck pain in air force pilots; however,
      the causes are not clear and are considered work-related. Kyphotic changes in the
      cervical spine have been known to cause neck pain. In this study, we investigated
      the association between neck pain and cervical kyphosis in air force pilots.
      METHODS: This is a cross-sectional study of 63 Republic of South Korea Air Force
      pilots. We examined the C2-7 absolute rotation angle (ARA) using the posterior
      tangent method and other radiologic parameters on whole spine lateral
      radiographs. We divided the participants into a neck pain group (N = 32) and no
      neck pain group (N = 31), and subsequently analyzed the difference in
      radiographic parameters and clinical data between the two groups. RESULTS: There
      were no significant differences found in age, body mass index, total flight time,
      or aerobic or anaerobic exercise between the neck pain and control groups. The
      fighter pilots had higher 1-yr prevalence of neck pain than nonfighter pilots
      (84.4% vs. 15.6%). The lower C2-7 ARA (OR = 0.91, 95% CI 0.846, 0.979) and
      fighter type aircrafts (OR = 3.93, 95% CI 1.104, 13.989) were associated with
      neck pain. CONCLUSIONS: Fighter pilots experienced neck pain more frequently than
      the nonfighter pilots. Those fighter pilots suffering from neck pain were shown
      to have more kyphotic changes in the cervical spine than control pilots through
      evaluation of whole spine lateral radiographs using the posterior tangent method.
      These key findings suggest that the forces involved in flying a fighter type
      aircraft may affect cervical alignment and neck pain.

PMID- 25945662
TI  - Diaphragmatic breathing and its effectiveness for the management of motion
      sickness.
AB  - BACKGROUND: Motion sickness is an unpleasant physiological state that may be
      controlled via nonpharmacological methods. Controlled breathing has been shown to
      maximize parasympathetic nervous system (PNS) tone and may have the ability to
      decrease motion sickness symptoms. METHODS: The effects of slow diaphragmatic
      breathing (DB) in a motion sickness-inducing environment were examined within
      motion sickness susceptible individuals. Subjects (N = 43) were assigned randomly
      to either an experimental group trained in slow DB or a control group breathing
      naturally at a normal pace. The experimental group was trained using a digital
      video that helped them pace their diaphragmatic breathing at six breaths/min.
      During the study, subjects viewed a virtual reality (VR) experience of a boat in
      rough seas for 10 min. Motion sickness ratings along with heart rate and
      respiration rate were collected before, during, and after the VR experience.
      RESULTS: Results indicated that the experimental group was able to decrease their
      breathing to eight breaths/min during the VR experience. This breathing rate was
      significantly slower than those in the control group. We found that DB subjects,
      compared to those in the control group, displayed significantly greater heart
      rate variability and reported feeling less motion sickness during exposure to the
      VR experience than those in the control group. DISCUSSION: Results indicate
      possible benefits of using slow DB techniques in a motion sickness inducing
      environment.

PMID- 25945663
TI  - Medical symptoms among pilots associated with work and home environments: a 3
      year cohort study.
AB  - OBJECTIVE: To study associations between the cockpit environment, psychosocial
      work environment, home environment, and medical symptoms in a cohort of
      commercial pilots followed over 3 yr. METHODS: A standardized questionnaire was
      mailed in February-March 1997 to all Stockholm-based pilots on duty in a
      Scandinavian flight company (N = 622); 577 (93%) participated. During this time
      smoking was allowed on long haul flights, but not on shorter flights. Smoking was
      prohibited on all flights after September 1997. The same questionnaire was sent
      to the cohort of 577 pilots in February-March 2000; 436 participated (76%). The
      questionnaire contained questions on symptoms, the psychosocial work environment,
      and the home environment. Associations were investigated using multiple logistic
      and ordinal regression. RESULTS: Symptoms were common, especially eye symptoms
      (38.5%), nose symptoms (39.9%), and tiredness (29.9%). Pilots exposed to
      environmental tobacco smoke (ETS) on long haul flights had more eye symptoms
      (odds ratio = 1.91) and tiredness (odds ratio = 2.73). These symptoms were
      reduced when no longer exposed to ETS. Those who started working on long haul
      flights developed more nose symptoms. Pilots reporting increased work demands
      developed more nose and dermal symptoms and tiredness and those with decreased
      work control developed more eye symptoms. Pilots living in new houses,
      multifamily houses, and in recently painted homes reported more symptoms.
      CONCLUSION: Eliminating ETS exposure on board reduced medical symptoms. Further
      work to reduce ETS exposure globally is needed. Psychosocial aspects of the work
      environment for commercial pilots should be considered, as well as the home
      environment.

PMID- 25945664
TI  - Restraint harness performance during flight maneuvers: a parametric study.
AB  - INTRODUCTION: Modern super agile fighter aircraft are capable of producing an
      increasing multiaxial acceleration environment which can adversely affect the
      pilot. An evaluation of the performance of the restraint system during flight
      maneuvers will benefit restraint designs and, thus, the safety of pilots.
      METHODS: A finite element model of a mannequin with PCU-15/P harness restraint
      was used in this study to investigate how the factors, such as strap material
      stiffness, friction, and belt tension, affect the performance of restraint
      systems during impact along the -Gx, -Gy, and -Gz directions. The corresponding
      maximum displacement of the mannequin's torso was computed. RESULTS: The
      mannequin moved beyond 74 mm sideways. The change in friction coefficient (FC)
      from 0.1 to 0.4 decreased the displacement of the lower torso by less than 6.7%.
      The displacement of the torso decreased as the stiffness of the strap or tension
      increased. Displacement decreased by 9.3%, 6.0%, and 2.7% for the lower torso
      under the Gx impact, as the tightening force increased from 20 N to 80 N
      gradually. However, this changed slightly when the stiffness arrived at 1 E or
      the tension increased to 60 N. DISCUSSION: PCU-15/P harness has the poorest
      performance during side impact and friction plays an unimportant role in
      affecting its performance. The stiffness of the webbing used in the PCU-15/P
      harness is sufficiently high. The lap belt has more effect on limiting the
      movement of the pilot than the shoulder straps, and a tension of 60 N during the
      adjustment may be enough for conventional flight maneuvers.

PMID- 25945665
TI  - Kidney function and urine protein composition in healthy volunteers during space
      station fitness tests.
AB  - BACKGROUND: There is a close physiological connection between muscular activity
      and kidney function. During physical exercise (PE) the qualitative and
      quantitative composition of urine changes. This paper explores the influence of
      moderate PE on urine protein composition. The study of urine protein composition
      will help to make corrections to the existing methods of countermeasures.
      METHODS: There were 10 healthy men who exercised on a treadmill similar to the
      one onboard the International Space Station. We analyzed their urinary proteome
      composition, potassium level, sodium level, and their level of osmotically active
      substances before and after PE. RESULTS: After moderate PE, a small increase in
      urine flow speed and a constant glomerular filtration rate were noted. The
      average-group index of total protein excretion within the urine was reliably
      increased. From the 148 proteins identified in the urine, 64 were associated with
      known tissue origin. We found that protein penetration into the urine had a
      positive correlation with their tissue expression. Selectivity of the glomerular
      barrier during PE decreased and high-molecular weight proteins penetrated through
      the glomerular barrier more easily after PE. DISCUSSION: Performance of moderate
      intensity physical exercise of short duration did not lead to an increase in the
      glomerular filtration rate nor did diuresis increase above the limits of baseline
      variability. However, the protein excretion rate increased after PE. We also
      observed that protein composition drift indicated a change in the set of
      biological processes in which a given protein participated, in some cases
      activating, in some cases inactivating them.

PMID- 25945666
TI  - An incidental suprasellar mass in a military flying cadet: implications for
      aircrew.
AB  - BACKGROUND: Incidental findings pose a dilemma in aviation medicine, where every
      finding must be carefully considered in order to ensure the well-being of the
      aircrew for flight and mission safety. Since suprasellar masses are not uncommon,
      their possible effects should be addressed. CASE REPORT: We present an incidental
      finding of 11.5 mm * 14.4 mm, hyper-intense on T2 and iso-intense on T1-weighted
      images, of a suprasellar mass in a 19-yr-old man. This finding led to the re
      evaluation of his position as a military flight cadet, followed by his later
      disqualification. DISCUSSION: No medical waiver regarding asymptomatic
      suprasellar mass exists. We have carefully examined the differential diagnosis
      and generated a profile for each possible diagnosis consisting of risks for
      sudden incapacitation, progression likelihood, and the effect of an aerial
      environment on a brain lesion. We were able to draw up a medical waiver for some
      of the possible diagnoses (namely, Rathke's cyst or craniopharyngioma) for
      nonhigh performance aircraft.

PMID- 25945667
TI  - A 6-month assessment of sleep during naval deployment: a case study of a
      commanding officer.
AB  - BACKGROUND: Sleep deprivation is known to be a common problem in the U.S. Navy
      and has been documented using wrist-worn actigraphy in various operational
      studies that typically span 2 to 4 wk in duration. However, sleep patterns over
      an extended period of time have not been objectively measured. CASE REPORT: This
      6-mo study used actigraphy and the Fatigue Avoidance Scheduling Tool (FAST) to
      quantify the sleep patterns of a 39-yr-old Commanding Officer (CO) of an Arleigh
      Burke class destroyer while the ship was forward-deployed. On average, the CO
      received 5.2 h of sleep daily and averaged 6 h time in bed each day. The
      participant received more than 8 h of sleep for only 2% (N = 3) of the study
      days; for 17% (N = 27) of the days, he received less than 4 h of daily sleep. For
      15% of waking time, the CO had a predicted effectiveness of less than 70% on the
      FAST scale, equating to a blood alcohol equivalent of 0.08%-or legally drunk. The
      CO's predicted effectiveness was below 65% approximately 10% of waking time.
      DISCUSSION: Results from this study are aligned with earlier research showing
      that crewmembers on U.S. Navy ships suffer from chronic sleep restriction. During
      a typical deployment, personnel accrue a considerable sleep debt even during
      normal operations. Should critical events with additional sleep restriction
      occur, the ship has limited reserve capacity, potentially placing her crew and
      their mission in grave jeopardy.

PMID- 25945668
TI  - AsMA Medical Guidelines for Air Travel: stresses of flight.
AB  - INTRODUCTION: Medical Guidelines for Airline Travel provide information that
      enables healthcare providers to properly advise patients who plan to travel by
      air. Modern commercial aircraft are very safe and, in most cases, reasonably
      comfortable. However, all flights, short or long haul, impose stresses on
      passengers. Preflight stresses include airport commotion on the ground such as
      carrying baggage, walking long distances, getting to the gate on time, and being
      delayed. In-flight stresses include acceleration, vibration (including
      turbulence), noise, lowered barometric pressure, variations of temperature and
      humidity, and fatigue among others. Healthy passengers normally tolerate these
      stresses quite well; however, there is the potential for passengers to become ill
      during or after the flight due to these stresses, especially for those with pre
      existing medical conditions and reduced physiological reserves.

PMID- 25945669
TI  - Letter to the Editor re: Flying after diving: in-flight echocardiography after a
      scuba diving week: letter.

PMID- 25945670
TI  - Letter to the Editor re: Flying after diving: in-flight echocardiography after a
      scuba diving week: response.

PMID- 25945671
TI  - Letter to the Editor re: Risk of prostate cancer in pilots: a meta-analysis:
      letter.

PMID- 25945672
TI  - Letter to the Editor re: Risk of prostate cancer in pilots: a meta-analysis:
      response.

PMID- 25945673
TI  - Retraction.

PMID- 25945674
TI  - Reviews.

PMID- 25945675
TI  - Reviews.

PMID- 25945676
TI  - Pulse oximeter signal fusion for robust hypoxia detection.

PMID- 25945677
TI  - You're the Flight Surgeon: hand, foot, and mouth disease.
AB  - Howard CT, Vu P. You're the flight surgeon: hand, foot, and mouth disease. Aerosp
      Med Hum Perform. 2015; 86(5):497-500. 

PMID- 25945678
TI  - You're the Flight Surgeon: epilepsy.
AB  - Woolford JS. You're the flight surgeon: epilepsy. Aerosp Med Hum Perform. 2015;
      86(4):500-503. 

PMID- 25945679
TI  - Development of Telemedicine and NASA's Contribution.

PMID- 25945680
TI  - This month in aerospace medicine history.

PMID- 25945681
TI  - An experimental-computer modeling study of inorganic phosphates surface
      adsorption on hydroxyapatite particles.
AB  - The adsorption of orthophosphate, pyrophosphate, triphosphate and a
      trisphosphonate onto hydroxyapatite has been examined using experiments and
      quantum mechanical calculations. Adsorption studies with FTIR and X-ray
      photoelectron spectroscopies have been performed considering both crystalline
      hydroxyapatite (HAp) and amorphous calcium phosphate particles, which were
      specifically prepared and characterized for this purpose. Density functional
      theory (DFT) calculations have been carried out considering the (100) and (001)
      surfaces of HAp, which were represented using 1 * 2 * 2 and 3 * 3 * 1 slab
      models, respectively. The adsorption of phosphate onto the two crystallographic
      surfaces is very much favored from an energetic point of view, which is fully
      consistent with current interpretations of the HAp growing process. The
      structures calculated for the adsorption of pyrophosphate and triphosphate
      evidence that this process is easier for the latter than for the former. Thus,
      the adsorption of pyrophosphate is severely limited by the surface geometry while
      the flexibility of triphosphate allows transforming repulsive electrostatic
      interactions into molecular strain. On the other hand, calculations predict that
      the trisphosphonate only adsorbs onto the (001) surface of HAp. Theoretical
      predictions are fully consistent with experimental data. Thus, comparison of DFT
      results and spectroscopic data suggests that the experimental conditions used to
      prepare HAp particles promote the predominance of the (100) surface. Accordingly,
      experimental identification of the adsorption of trisphosphonate onto such
      crystalline particles is unclear while the adsorption of pyrophosphate and
      triphosphate is clearly observed. 

PMID- 25945682
TI  - Direct-synthesis method towards copper-containing periodic mesoporous
      organosilicas: detailed investigation of the copper distribution in the material.
AB  - Three-dimensional cubic Fm3[combining macron]m mesoporous copper-containing
      ethane-bridged PMO materials have been prepared through a direct-synthesis method
      at room temperature in the presence of cetyltrimethylammonium bromide as
      surfactant. The obtained materials have been unambiguously characterized in
      detail by several sophisticated techniques, including XRD, UV-Vis-Dr, TEM,
      elemental mapping, continuous-wave and pulsed EPR spectroscopy. The results show
      that at lower copper loading, the Cu(2+) species are well dispersed in the Cu-PMO
      materials, and mainly exist as mononuclear Cu(2+) species. At higher copper
      loading amount, Cu(2+) clusters are observed in the materials, but the
      distribution of the Cu(2+) species is still much better in the Cu-PMO materials
      prepared through the direct-synthesis method than in a Cu-containing PMO material
      prepared through an impregnation method. Moreover, the evolution of the copper
      incorporation during the PMO synthesis has been followed by EPR. The results show
      that the immobilization of the Cu(2+) ion/complex and the formation of the PMO
      materials are taking place simultaneously. The copper ions are found to be
      situated on the inner surface of the mesopores of the materials and are
      accessible, which will be beneficial for the catalytic applications. 

PMID- 25945684
TI  - Effect of subjective economic status on psychological distress among farmers and
      non-farmers of rural China.
AB  - OBJECTIVE: This study aims to compare the prevalence of psychological distress
      between farmers and non-farmers of rural China. Further, this examines the effect
      of subjective economic status on psychological distress and whether this effect
      varies between farmers and non-farmers. DESIGN: The study design is a cross
      sectional survey. SETTING: The study was conducted in 27 villages of Dongying
      City in Shandong Province. PARTICIPANTS: Rural employed people included 1433
      farmers and 584 non-farmers. MAIN OUTCOME MEASURES: Psychological distress was
      assessed by the Kessler 10 questionnaire, and subjective economic status was
      assessed by a single question. RESULTS: Overall, the farmers did not report
      significantly higher prevalence of psychological distress than non-farmers
      (31.13% versus 30.01%). However, the farmers aged 51-70 years did report
      significantly higher psychological distress than their non-farmer counterparts
      (33.4% versus 24.2%, P = 0.04). Second, subjective economic status had a
      significant (beta = -0.28, P < 0.001) effect on psychological distress. Finally,
      subjective economic status exerted a stronger effect on psychological distress
      among farmers (beta = 0.30, P < 0.001) than among non-farmers (beta = 0.20, P <
      0.001). CONCLUSIONS: The farmers had a comparable prevalence of psychological
      distress when compared with non-farmers in rural China. Subjective economic
      status exerted a significant effect on the psychological distress of rural
      employed people, and this effect was stronger for the farmers than for the non
      farmers.

PMID- 25945683
TI  - Behavioral Abnormalities in Lagotto Romagnolo Dogs with a History of Benign
      Familial Juvenile Epilepsy: A Long-Term Follow-Up Study.
AB  - BACKGROUND: Lagotto Romagnolo (LR) dogs with benign juvenile epilepsy syndrome
      often experience spontaneous remission of seizures. The long-term outcome in
      these dogs currently is unknown. In humans, behavioral and psychiatric
      comorbidities have been reported in pediatric and adult-onset epilepsies.
      HYPOTHESIS/OBJECTIVES: The objectives of this study were to investigate possible
      neurobehavioral comorbidities in LR with a history of benign familial juvenile
      epilepsy (BFJE) and to assess the occurrence of seizures after the remission of
      seizures in puppyhood. ANIMALS: A total of 25 LR with a history of BFJE and 91
      control dogs of the same breed. METHODS: Owners of the LR dogs in the BFJE and
      control groups completed an online questionnaire about each dog's activity,
      impulsivity, and inattention. Principal component analysis (PCA) served to
      extract behavioral factors from the data. We then compared the scores of these
      factors between the 2 groups in a retrospective case-control study. We also
      interviewed all dog owners in the BFJE group by telephone to inquire specifically
      about possible seizures or other neurological problems after remission of
      seizures as a puppy. RESULTS: Lagotto Romagnolo dogs with BFJE showed
      significantly higher scores on the factors Inattention and
      Excitability/Impulsivity than did the control group (P = .003; P = .021,
      respectively). Only 1 of the 25 BFJE LR exhibited seizures after remission of
      epilepsy in puppyhood. CONCLUSIONS AND CLINICAL IMPORTANCE: Although the long
      term seizure outcome in BFJE LR seems to be good, the dogs exhibit behavioral
      abnormalities resembling attention deficit hyperactivity disorder (ADHD) in
      humans, thus suggesting neurobehavioral comorbidities with epilepsy.

PMID- 25945685
TI  - Characterizing titanium dioxide and zinc oxide nanoparticles in sunscreen spray.
AB  - OBJECTIVE: Numerous commercial products contain titanium dioxide (TiO2 ) and zinc
      oxide (ZnO) nanoparticles (NPs); however, many of these are not labelled as
      containing NPs. This study sought to develop an effective means of characterizing
      TiO2 and ZnO NPs in sunscreen sprays, including the size, shape and composition
      of the particles as well as their aggregation/agglomeration characteristics.
      METHODS: Transmission electron microscopy (TEM) coupled with a window-type
      microchip K-kit/copper grid and X-ray diffraction (XRD) was used to characterize
      the oxide NPs. RESULTS: TME pre-treatment was performed using two approaches:
      using a conventional copper grid (requiring dilution) and using a K-kit (not
      requiring dilution). The use of K-kit in conjunction with XRD makes it possible
      to obtain direct measurements from samples that have not undergone pre-treatment,
      which could otherwise alter the nature of the samples, such as the degree of
      agglomeration. XRD was used to obtain information related to particle size and
      crystal structure. A strong correlation was observed between XRD and TEM
      measurements. CONCLUSION: The proposed measurement methods were shown to be
      highly effective in the characterization of oxide NPs in sunscreen sprays,
      providing consistent information related to NPs and their interactions in the
      formulations.

PMID- 25945687
TI  - Inclusion of two push-pull N-methylpyridinium salts in anionic surfactant
      solutions: a comprehensive photophysical investigation.
AB  - Two N-methylpyridinium salts with push-pull properties have been investigated in
      the aqueous solution of anionic micelles of sodium dodecyl sulfate (SDS) and
      potassium p-(octyloxy)benzenesulfonate (pOoBSK) surfactants. These molecules are
      known to be extremely sensitive to the local environment, with their absorption
      spectrum being subjected to a net negative solvatochromism. These compounds are
      also characterized by an excited state deactivation strictly dependent on the
      physical properties of the chemical surrounding, with the formation of
      intramolecular charge-transfer (ICT) states accordingly stabilized. Thanks to
      steady-state and femtosecond resolved spectroscopic techniques, the photophysical
      properties of these molecules in the presence of anionic micelles have been fully
      characterized and an efficient permeation within the micellar aggregates can thus
      be inferred. The extent of the changes in the photophysical properties of these
      molecules (with respect to what is observed in water) is an indicator of the
      medium experienced in the nanoheterogeneous solutions: enhanced fluorescence
      emissions, reduced Stokes shifts and slowed-down excited state decays strongly
      confirm the confinement within a scarcely polar and restraining environment. The
      slightly different behavior shown in the two types of micelles can be ascribed to
      a peculiar interaction between the aromatic moiety of the surfactant and that of
      the cations. Additionally, the inclusion promotes the solubilization of these
      poorly water-soluble salts, which is alluring in their promising use as DNA
      binders for antitumor purposes. Thus, the anionic micelles allowed the
      solubilization of the pyridinium salts under investigation, which in turn allowed
      the characterization of the nonhomogeneous medium established by the micellar
      aggregates. 

PMID- 25945688
TI  - High Risk Retinoblastoma: Prevalence and Success of Treatment in Developing
      Countries.

PMID- 25945689
TI  - Prognostic value of aortic root calcification volume on clinical outcomes after
      transcatheter balloon-expandable aortic valve implantation.
AB  - BACKGROUND: Few data are available about whether aortic root calcification may
      impact the outcomes after transcatheter aortic valve implantation (TAVI).
      OBJECTIVES: This study sought to evaluate the impact of aortic root calcification
      volume on clinical outcome after TAVI with balloon expandable Edwards Sapien XT
      valve (Edwards Lifesciences, Irvine, California). METHODS: A total of 162 TAVI
      patients (aged 84.0 [Interquartile Range (IQR) 81.0-84.0] years, Logistic
      EuroSCORE 14.5 [IQR 9.8-25.1]) with preprocedural MDCT were studied. Aortic root
      calcification volume was measured by MDCT image and using the dedicated software
      for aortic valve assessment (the automated 3mensioTM Valves 5.1, sp1, 3mensio Pie
      Medical Imaging BV, Maastricht, the Netherlands). A valve calcification index
      (VCI) was defined as calcification volume (mm(3))/body surface area (mm(2)).
      RESULTS: VCI was significantly higher among patients with 30-day mortality. A VCI
      threshold of 517.4 (area under the curve 0.69, 95% CI 0.50-0.87, P = 0.03)
      predicted a higher incidence of annulus rupture (9.1 vs. 0.9%, P = 0.02) and
      cardiac tamponade (12.7 vs. 1.9%, P < 0.01), lower device success (83.6% vs.
      95.3%, P < 0.01) and 30-day survival rate (80.0% vs. 97.2%, P < 0.01).
      Multivariate logistic regression analysis showed only ejection fraction and VCI
      were identified as independent predictors of 30-day mortality (Odds ratio 0.948
      [95% confidence interval 0.909-0.988], P = 0.012, Odds ratio 1.003 [95%
      confidence interval 1.001-1.005], P = 0.013, respectively). CONCLUSIONS:
      Significantly worse acute clinical outcomes after Edwards valve implantation were
      observed in patients with large amount of aortic annulus calcifications
      quantitatively measured by dedicated MDCT software. Application of VCI may prove
      helpful in prediction of clinical outcomes after TAVI.

PMID- 25945690
TI  - Modulation of cellular function through immune-activated exosomes.
AB  - Extracellular vesicles classified as exosomes, microvesicles, or apoptotic bodies
      based on size are shed from most cells under normal as well as pathological
      conditions. They are released into the surrounding milieu, including plasma,
      urine, saliva, and tissues. Exosomes are highly enriched in microRNAs (miRs),
      which function in recipient cells by regulating posttranscriptional processing of
      targeted genes. Interaction of a miR with its mRNA target typically results in
      suppression of its gene expression. Peripheral inflammatory conditions can
      modulate miR expression in immune cells such as circulating monocytes that can
      influence their migration and differentiation. Changes within monocyte-derived
      macrophage miR expression can influence exosome content and further affect end
      organ target cells. 

PMID- 25945691
TI  - Effect of steroids for nasal polyposis surgery: A placebo-controlled, randomized,
      double-blind study.
AB  - OBJECTIVES/HYPOTHESIS: Although medical intervention is the first option for
      treatment of nasal polyps, surgery is still a therapeutic option for symptomatic
      cases that do not respond or partially respond to medical intervention. However,
      there is a need for high-level evidence for the preoperative use of steroids in
      nasal polyposis surgery. We aimed to assess the perioperative effect of
      preoperative use of oral prednisolone for advanced-stage diffuse nasal polyposis.
      STUDY DESIGN: Prospective, double-blind, randomized, placebo-controlled study.
      METHODS: A visual analog scale (VAS) was evaluated for smell, nasal discharge,
      nasal obstruction, facial pressure, headache, butanol smell threshold, and peak
      nasal inspiratory flow (PNIF) before and after the use of study drug.
      Perioperative bleeding volume, visibility of operative field, operative time,
      hospital stay, and complication rate were also evaluated. RESULTS: The
      improvement in the corticosteroid group (CG) in the VAS scores, butanol
      thresholds, and PNIF values showed statistically significant differences compared
      to the placebo group (PG) (P < .05). The perioperative bleeding volume,
      visibility score, operative time, and hospital stay for CG/PG were 141 mL/384 mL,
      2.4/3.4, 61 min/71.6 min, and 1.1 day/1.8 day, respectively (P < .05). The
      difference between the complication rates for the two groups did not show any
      statistically significant difference (P = .214). CONCLUSIONS: Preoperative
      administration of systemic corticosteroids improves the perioperative visibility
      by reducing blood loss and shortens the operation time. We recommend the use of
      preoperative corticosteroid for the safety of the patients. The optimum dose and
      duration have not been established and require further studies. LEVEL OF
      EVIDENCE: 1b.

PMID- 25945692
TI  - Enhancing the Quality of Prescribing Practices for Older Veterans Discharged from
      the Emergency Department (EQUiPPED): Preliminary Results from Enhancing Quality
      of Prescribing Practices for Older Veterans Discharged from the Emergency
      Department, a Novel Multicomponent Interdisciplinary Quality Improvement
      Initiative.
AB  - Suboptimal medication prescribing for older adults has been described in a number
      of emergency department (ED) studies. Despite this, few studies have examined ED
      targeted interventions aimed at reducing the use of potentially inappropriate
      medications (PIMs). Enhancing Quality of Prescribing Practices for Older Veterans
      Discharged from the ED (EQUiPPED) is an ongoing multicomponent, interdisciplinary
      quality improvement initiative in eight Department of Veterans Affairs EDs. The
      project aims to decrease the use of PIMs, as identified by the Beers criteria,
      prescribed to veterans aged 65 and older at the time of ED discharge.
      Interventions include provider education; informatics-based clinical decision
      support with electronic medical record-embedded geriatric pharmacy order sets and
      links to online geriatric content; and individual provider education including
      academic detailing, audit and feedback, and peer benchmarking. Poisson regression
      was used to compare the number of PIMs that staff providers prescribed to
      veterans aged 65 and older discharged from the ED before and after the initiation
      of the EQUiPPED intervention. Initial data from the first implementation site
      show that the average monthly proportion of PIMs that staff providers prescribed
      was 9.4+/-1.5% before the intervention and 4.6+/-1.0% after the initiation of
      EQUiPPED (relative risk=0.48, 95% confidence interval=0.40-0.59, P<.001).
      Preliminary evaluation demonstrated a significant and sustained reduction of ED
      prescribed PIMs in older veterans after implementation of EQUiPPED. Longer follow
      up and replication at collaborating sites would allow for an assessment of the
      effect on health outcomes and costs.

PMID- 25945693
TI  - Characterization of Inhibitor-Resistant TEM beta-Lactamases and Mechanisms of
      Fluoroquinolone Resistance in Escherichia coli Isolates.
AB  - The aim of present work was to characterize the inhibitor-resistant TEM (IRT)
      beta-lactamases produced by Escherichia coli in Hospital Clinico San Carlos
      (Madrid, Spain). Mechanisms of fluoroquinolone resistance among IRT-producing
      strains were also studied. Isolates with susceptibility to cephalosporins and
      amoxicillin-clavulanate (AMC) resistance were collected in our hospital (November
      2011-July 2012) from both outpatients and hospitalized patients. Among 70 AMC
      resistant E. coli strains, 28 (40%) produced IRT enzymes. Most of them were
      uropathogens (82.1%) and recovered from outpatients (75%). Seven different IRT
      enzymes were identified with TEM-30 (IRT-2) being the most prevalent, followed by
      TEM-40 (IRT-11). A high rate of ciprofloxacin resistance was found among IRT
      producing strains (50%). Most of the ciprofloxacin-resistant isolates showed
      ciprofloxacin minimum inhibitory concentration >32 mg/L and contained two
      mutations in both gyrA and parC genes. Four IRT enzyme producers harbored the qnr
      gene. ST131 clone was mainly responsible for both IRT enzyme production and
      ciprofloxacin resistance. In conclusion, data from this study show that the
      frequency of IRT producers was 40% and a high rate of ciprofloxacin resistance
      was found among IRT-producing isolates. Current and future actions should be
      taken into account to avoid or reduce the development of AMC and fluoroquinolone
      resistance in E. coli. 

PMID- 25945694
TI  - One-Pot Synthesis of Mesoporous TiO2 Micropheres and Its Application for High
      Efficiency Dye-Sensitized Solar Cells.
AB  - TiO2 microspheres are of great interest for a great deal of applications,
      especially in the solar cell field. Because of their unique microstructure and
      light-scattering effect, TiO2 microsphere-based solar cells often exhibit
      superior photovoltaic performance. Hence, exploring new suitable TiO2
      microspheres for high-efficiency solar cells is essential. In this work, we
      demonstrate a facile one-pot solvothermal approach for synthesis of TiO2
      microspheres using acetone as solvent. The as-prepared TiO2 microspheres are
      composed of densely interconnected nanocrystals and possess a high specific
      surface area up to 138.47 m(2) g(-1). As the photoanode, the TiO2 microsphere
      based DSSC gives higher dye loading and light adsorption ability as well as
      longer electron lifetime, resulting in higher short-circuit current value and
      superior power conversion efficiency (PCE) compared with Dyesol 18 nm TiO2
      nanoparticle paste. Finally, the TiO2 microsphere-based DSSC were optimized by
      adding a TiO2 nanocrystal underlayer and TiCl4 post-treatment, giving a high PCE
      of 10.32%. 

PMID- 25945695
TI  - Activated cdc42-associated kinase is up-regulated in non-small-cell lung cancer
      and necessary for FGFR-mediated AKT activation.
AB  - Activated cdc42-associated tyrosine kinase 1 (ACK1) has been reported to be
      implicated in non-small-cell lung cancer (NSCLC). However, the expression pattern
      and biological functions of ACK1 in the progression of NSCLC are not fully
      understood. In this study, it was found that the expression of ACK1 was
      significantly up-regulated in NSCLC samples compared to their adjacent normal
      tissues. Meanwhile, the expression of ACK1 was inversely correlated with the
      survival of NSCLC patients. Moreover, in the biological function studies, ACK1
      was further validated to promote the growth, migration, and metastasis of NSCLC
      cells in vitro and in vivo. Mechanistically, ACK1 bind with FGFR1 and was
      essential for the phosphorylation of AKT induced by FGF. Our study demonstrated
      that ACK1 played an oncogenic role in the progression of NSCLC and ACK1 might be
      a promising target for the treatment of NSCLC.

PMID- 25945696
TI  - Breastfeeding over two years is associated with longer birth intervals, but not
      measures of growth or health, among children in Kilimanjaro, TZ.
AB  - OBJECTIVES: Breastfeeding has been associated with numerous health and well-being
      benefits for both children and their mothers, including prolonging the birth
      interval to the subsequent sibling. The clearest associations between
      breastfeeding and health outcomes, per se, reflect exclusive breastfeeding in the
      first months of postnatal life and are most evident during infancy. Fewer studies
      explore the consequences of breastfeeding for multiple years. In this article, we
      ask whether breastfeeding for more than 2 years is associated with discernible
      health and well-being benefits to children. METHODS: Data were collected from 315
      children, aged 2 to 7, and their caretakers residing in Kilimanjaro, Tanzania.
      Basic demographic and health information was solicited, and anthropometric and
      blood markers of health were evaluated. RESULTS: Our results indicate a strong
      positive relationship between breastfeeding for 2 or more years and interbirth
      interval, but little evidence for a relationship between prolonged breastfeeding
      and several indicators of child growth and health. CONCLUSIONS: We suggest that
      these relationships may support the recently rekindled birth spacing hypothesis,
      positing selection for longer interbirth intervals, rather than, or in addition
      to, more direct health benefits associated with breastfeeding for 2 or more
      years. Our results may indicate attenuating health benefits associated with
      longer breastfeeding.

PMID- 25945697
TI  - Controlled Synthesis of 1,3,5-Oxadiazin-2-ones and Oxazolones through
      Regioselective Iodocyclization of Ynamides.
AB  - Two efficient processes based on the iodocyclization of ynamides have been
      developed: (i) N-alkynyl tert-butyloxycarbamates were found to undergo a rare 6
      exo-dig ring closure reaction affording 1,3,5-oxadiazin-2-ones by using
      acetonitrile as solvent; (ii) In the absence of acetonitrile, N-alkynyl tert
      butyloxycarbamates could undergo 5-endo-dig cyclization providing oxazolones. 

PMID- 25945699
TI  - Does shared genetic risk contribute to the co-occurrence of eating disorders and
      suicidality?
AB  - OBJECTIVE: There is a high level of co-occurrence of suicidality with eating
      disorders (EDs) but the reason for this is unknown. To test the hypothesis that
      suicidality and EDs share genetic risk contributing to the expression of both
      phenotypes. METHOD: Female twins (N = 1,002) from the Australian Twin Registry,
      aged 28-40 years, were interviewed with diagnostic interviews. Lifetime
      diagnostic information relating to eating disorders [anorexia nervosa (AN),
      bulimia nervosa (BN), binge eating disorder, and purging disorder (PD)],
      suicidality (ranging transitory thoughts to suicide attempts), and major
      depression. RESULTS: Any suicidal thoughts were reported by 24% of the sample,
      but prevalence of lifetime suicidality among female twins with EDs was much
      higher (43%), presence of an ED diagnosis more than doubling likelihood of
      suicidality (OR = 2.32, 95% CI: 1.63-3.31). AN and BN conveyed greatest risk of
      suicidality (OR = 2.03, 95% CI: 1.06-3.87; OR = 3.97, 95% CI: 2.01-7.85,
      respectively). Twin phenotype correlations showed monozygotic twins had uniformly
      higher estimates than dizygotic counterparts. A trivariate Cholesky model
      indicated a common genetic influence on suicidality and ED phenotypes (but not
      depression), and no nonshared environmental source. DISCUSSION: Both cross twin
      phenotypic correlations and genetic modeling infer a common genetic pathway for
      suicidality and EDs, but further investigation is needed to elucidate whether
      this may constitute emotional dysregulation or other temperament-linked factors.
      Study findings also indicate that ED clients must be routinely assessed for
      presence of suicidality, independent of depression status.

PMID- 25945700
TI  - Macromolecular crystallography and what it can contribute to antiparasite drug
      discovery.

PMID- 25945698
TI  - Pregnancy distress gets under fetal skin: Maternal ambulatory assessment & sex
      differences in prenatal development.
AB  - Prenatal maternal distress is associated with an at-risk developmental profile,
      yet there is little fetal evidence of this putative in utero process. Moreover,
      the biological transmission for these maternal effects remains uncertain. In a
      study of n = 125 pregnant adolescents (ages 14-19), ambulatory assessments of
      daily negative mood (anger, frustration, irritation, stress), physical activity,
      blood pressure, heart rate (every 30 min over 24 hr), and salivary cortisol (six
      samples) were collected at 13-16, 24-27, 34-37 gestational weeks. Corticotropin
      releasing hormone, C-reactive protein, and interleukin 6 from blood draws and 20
      min assessments of fetal heart rate (FHR) and movement were acquired at the
      latter two sessions. On average, fetuses showed development in the expected
      direction (decrease in FHR, increase in SD of FHR and in the correlation of
      movement and FHR ("coupling")). Maternal distress characteristics were associated
      with variations in the level and trajectory of fetal measures, and results often
      differed by sex. For males, greater maternal 1st and 2nd session negative mood
      and 2nd session physical activity were associated with lower overall FHR (p <
      .01), while 1st session cortisol was associated with a smaller increase in
      coupling (p < .01), and overall higher levels (p = .05)-findings suggesting
      accelerated development. For females, negative mood, cortisol, and diastolic
      blood pressure were associated with indications of relatively less advanced and
      accelerated outcomes. There were no associations between negative mood and
      biological variables. These data indicate that maternal psychobiological status
      influences fetal development, with females possibly more variously responsive to
      different exposures.

PMID- 25945701
TI  - Three-dimensional structures in the design of therapeutics targeting parasitic
      protozoa: reflections on the past, present and future.
AB  - Parasitic protozoa cause a range of diseases which threaten billions of human
      beings. They are responsible for tremendous mortality and morbidity in the least
      developed areas of the world. Presented here is an overview of the evolution over
      the last three to four decades of structure-guided design of inhibitors, leads
      and drug candidates aiming at targets from parasitic protozoa. Target selection
      is a crucial and multi-faceted aspect of structure-guided drug design. The major
      impact of advances in molecular biology, genome sequencing and high-throughput
      screening is touched upon. The most advanced crystallographic techniques,
      including XFEL, have already been applied to structure determinations of drug
      targets from parasitic protozoa. Even cryo-electron microscopy is contributing to
      our understanding of the mode of binding of inhibitors to parasite ribosomes. A
      number of projects have been selected to illustrate how structural information
      has assisted in arriving at promising compounds that are currently being
      evaluated by pharmacological, pharmacodynamic and safety tests to assess their
      suitability as pharmaceutical agents. Structure-guided approaches are also
      applied to incorporate properties into compounds such that they are less likely
      to become the victim of resistance mechanisms. A great increase in the number of
      novel antiparasitic compounds will be needed in the future. These should then be
      combined into various multi-compound therapeutics to circumvent the diverse
      resistance mechanisms that render single-compound, or even multi-compound, drugs
      ineffective. The future should also see (i) an increase in the number of projects
      with a tight integration of structural biology, medicinal chemistry, parasitology
      and pharmaceutical sciences; (ii) the education of more 'medicinal structural
      biologists' who are familiar with the properties that compounds need to have for
      a high probability of success in the later steps of the drug-development process;
      and (iii) the expansion of drug-development capabilities in middle- and low
      income countries. 

PMID- 25945703
TI  - Solution-state NMR structure of the putative morphogene protein BolA (PFE0790c)
      from Plasmodium falciparum.
AB  - Protozoa of the genus Plasmodium are responsible for malaria, which is perhaps
      the most important parasitic disease to infect mankind. The emergence of
      Plasmodium strains resistant to current therapeutics and prophylactics makes the
      development of new treatment strategies urgent. Among the potential targets for
      new antimalarial drugs is the BolA-like protein PFE0790c from Plasmodium
      falciparum (Pf-BolA). While the function of BolA is unknown, it has been linked
      to cell morphology by regulating transcription in response to stress. Using an
      NMR-based method, an ensemble of 20 structures of Pf-BolA was determined and
      deposited in the PDB (PDB entry 2kdn). The overall topology of the Pf-BolA
      structure, alpha1-beta1-beta2-eta1-alpha2/eta2-beta3-alpha3, with the beta
      strands forming a mixed beta-sheet, is similar to the fold observed in other BolA
      structures. A helix-turn-helix motif similar to the class II KH fold associated
      with nucleic acid-binding proteins is present, but contains an FXGXXXL signature
      sequence that differs from the GXXG signature sequence present in class II KH
      folds, suggesting that the BolA family of proteins may use a novel protein
      nucleic acid interface. A well conserved arginine residue, Arg50, hypothesized to
      play a role in governing the formation of the C-terminal alpha-helix in the BolA
      family of proteins, is too distant to form polar contacts with any side chains in
      this alpha-helix in Pf-BolA, suggesting that this conserved arginine may only
      serve a role in guiding the orientation of this C-terminal helix in some BolA
      proteins. A survey of BolA structures suggests that the C-terminal helix may not
      have a functional role and that the third helix (alpha2/eta2) has a 'kink' that
      appears to be conserved among the BolA protein structures. Circular dichroism
      spectroscopy shows that Pf-BolA is fairly robust, partially unfolding when heated
      to 353 K and refolding upon cooling to 298 K. 

PMID- 25945702
TI  - Towards a molecular understanding of the apicomplexan actin motor: on a road to
      novel targets for malaria remedies?
AB  - Apicomplexan parasites are the causative agents of notorious human and animal
      diseases that give rise to considerable human suffering and economic losses
      worldwide. The most prominent parasites of this phylum are the malaria-causing
      Plasmodium species, which are widespread in tropical and subtropical regions, and
      Toxoplasma gondii, which infects one third of the world's population. These
      parasites share a common form of gliding motility which relies on an actin-myosin
      motor. The components of this motor and the actin-regulatory proteins in
      Apicomplexa have unique features compared with all other eukaryotes. This,
      together with the crucial roles of these proteins, makes them attractive targets
      for structure-based drug design. In recent years, several structures of
      glideosome components, in particular of actins and actin regulators from
      apicomplexan parasites, have been determined, which will hopefully soon allow the
      creation of a complete molecular picture of the parasite actin-myosin motor and
      its regulatory machinery. Here, current knowledge of the function of this motor
      is reviewed from a structural perspective. 

PMID- 25945704
TI  - Structure of a CutA1 divalent-cation tolerance protein from Cryptosporidium
      parvum, the protozoal parasite responsible for cryptosporidiosis.
AB  - Cryptosporidiosis is an infectious disease caused by protozoan parasites of the
      Cryptosporidium genus. Infection is associated with mild to severe diarrhea that
      usually resolves spontaneously in healthy human adults, but may lead to severe
      complications in young children and in immunocompromised patients. The genome of
      C. parvum contains a gene, CUTA_CRYPI, that may play a role in regulating the
      intracellular concentration of copper, which is a toxic element in excess. Here,
      the crystal structure of this CutA1 protein, Cp-CutA1, is reported at 2.0 A
      resolution. As observed for other CutA1 structures, the 117-residue protein is a
      trimer with a core ferrodoxin-like fold. Circular dichroism spectroscopy shows
      little, in any, unfolding of Cp-CutA1 up to 353 K. This robustness is
      corroborated by (1)H-(15)N HSQC spectra at 333 K, which are characteristic of a
      folded protein, suggesting that NMR spectroscopy may be a useful tool to further
      probe the function of the CutA1 proteins. While robust, Cp-CutA1 is not as stable
      as the homologous protein from a hyperthermophile, perhaps owing to a wide beta
      bulge in beta2 that protrudes Pro48 and Ser49 outside the beta-sheet. 

PMID- 25945705
TI  - Structure of Cryptosporidium IMP dehydrogenase bound to an inhibitor with in vivo
      antiparasitic activity.
AB  - Inosine 5'-monophosphate dehydrogenase (IMPDH) is a promising target for the
      treatment of Cryptosporidium infections. Here, the structure of C. parvum IMPDH
      (CpIMPDH) in complex with inosine 5'-monophosphate (IMP) and P131, an inhibitor
      with in vivo anticryptosporidial activity, is reported. P131 contains two
      aromatic groups, one of which interacts with the hypoxanthine ring of IMP, while
      the second interacts with the aromatic ring of a tyrosine in the adjacent
      subunit. In addition, the amine and NO2 moieties bind in hydrated cavities,
      forming water-mediated hydrogen bonds to the protein. The design of compounds to
      replace these water molecules is a new strategy for the further optimization of
      C. parvum inhibitors for both antiparasitic and antibacterial applications. 

PMID- 25945706
TI  - The structure of tubulin-binding cofactor A from Leishmania major infers a mode
      of association during the early stages of microtubule assembly.
AB  - Tubulin-binding cofactor A (TBCA) participates in microtubule formation, a key
      process in eukaryotic biology to create the cytoskeleton. There is little
      information on how TBCA might interact with beta-tubulin en route to microtubule
      biogenesis. To address this, the protozoan Leishmania major was targeted as a
      model system. The crystal structure of TBCA and comparisons with three
      orthologous proteins are presented. The presence of conserved features infers
      that electrostatic interactions that are likely to involve the C-terminal tail of
      beta-tubulin are key to association. This study provides a reagent and template
      to support further work in this area. 

PMID- 25945707
TI  - Recombinant production, crystallization and crystal structure determination of
      dihydroorotate dehydrogenase from Leishmania (Viannia) braziliensis.
AB  - The enzyme dihydroorotate dehydrogenase (DHODH) is a flavoenzyme that catalyses
      the oxidation of dihydroorotate to orotate in the de novo pyrimidine-biosynthesis
      pathway. In this study, a reproducible protocol for the heterologous expression
      of active dihydroorotate dehydrogenase from Leishmania (Viannia) braziliensis
      (LbDHODH) was developed and its crystal structure was determined at 2.12 A
      resolution. L. (V.) braziliensis is the species responsible for the mucosal form
      of leishmaniasis, a neglected disease for which no cure or effective therapy is
      available. Analyses of sequence, structural and kinetic features classify LbDHODH
      as a member of the class 1A DHODHs and reveal a very high degree of structural
      conservation with the previously reported structures of orthologous
      trypanosomatid enzymes. The relevance of nucleotide-biosynthetic pathways for
      cell metabolism together with structural and functional differences from the
      respective host enzyme suggests that inhibition of LbDHODH could be exploited for
      antileishmanicidal drug development. The present work provides the framework for
      further integrated in vitro, in silico and in vivo studies as a new tool to
      evaluate DHODH as a drug target against trypanosomatid-related diseases.

PMID- 25945708
TI  - The X-ray structure of Plasmodium falciparum dihydroorotate dehydrogenase bound
      to a potent and selective N-phenylbenzamide inhibitor reveals novel binding-site
      interactions.
AB  - Plasmodium species are protozoan parasites that are the causative agent of
      malaria. Malaria is a devastating disease, and its treatment and control have
      been hampered by the propensity of the parasite to become drug-resistant.
      Dihydroorotate dehydrogenase (DHODH) has been identified as a promising new
      target for the development of antimalarial agents. Here, the X-ray structure of
      P. falciparum DHODH bound to a potent and selective N-phenylbenzamide-based
      inhibitor (DSM59) is described at 2.3 A resolution. The structure elucidates
      novel binding-site interactions and shows how conformational flexibility of the
      enzyme leads to the ability to bind diverse chemical structures with high
      affinity. This information provides new insight into the design of high-affinity
      DHODH inhibitors for the treatment of malaria.

PMID- 25945709
TI  - Structure of uridine diphosphate N-acetylglucosamine pyrophosphorylase from
      Entamoeba histolytica.
AB  - Uridine diphosphate N-acetylglucosamine pyrophosphorylase (UAP) catalyzes the
      final step in the synthesis of UDP-GlcNAc, which is involved in cell-wall
      biogenesis in plants and fungi and in protein glycosylation. Small-molecule
      inhibitors have been developed against UAP from Trypanosoma brucei that target an
      allosteric pocket to provide selectivity over the human enzyme. A 1.8 A
      resolution crystal structure was determined of UAP from Entamoeba histolytica, an
      anaerobic parasitic protozoan that causes amoebic dysentery. Although E.
      histolytica UAP exhibits the same three-domain global architecture as other UAPs,
      it appears to lack three alpha-helices at the N-terminus and contains two amino
      acids in the allosteric pocket that make it appear more like the enzyme from the
      human host than that from the other parasite T. brucei. Thus, allosteric
      inhibitors of T. brucei UAP are unlikely to target Entamoeba UAPs.

PMID- 25945710
TI  - Structures of aspartate aminotransferases from Trypanosoma brucei, Leishmania
      major and Giardia lamblia.
AB  - The structures of three aspartate aminotransferases (AATs) from eukaryotic
      pathogens were solved within the Seattle Structural Genomics Center for
      Infectious Disease (SSGCID). Both the open and closed conformations of AAT were
      observed. Pyridoxal phosphate was bound to the active site via a Schiff base to a
      conserved lysine. An active-site mutant showed that Trypanosoma brucei AAT still
      binds pyridoxal phosphate even in the absence of the tethering lysine. The
      structures highlight the challenges for the structure-based design of inhibitors
      targeting the active site, while showing options for inhibitor design targeting
      the N-terminal arm. 

PMID- 25945711
TI  - Structures of a histidine triad family protein from Entamoeba histolytica bound
      to sulfate, AMP and GMP.
AB  - Three structures of the histidine triad family protein from Entamoeba
      histolytica, the causative agent of amoebic dysentery, were solved at high
      resolution within the Seattle Structural Genomics Center for Infectious Disease
      (SSGCID). The structures have sulfate (PDB entry 3oj7), AMP (PDB entry 3omf) or
      GMP (PDB entry 3oxk) bound in the active site, with sulfate occupying the same
      space as the alpha-phosphate of the two nucleotides. The C(alpha) backbones of
      the three structures are nearly superimposable, with pairwise r.m.s.d.s ranging
      from 0.06 to 0.13 A.

PMID- 25945712
TI  - Production, purification and crystallization of a trans-sialidase from
      Trypanosoma vivax.
AB  - Sialidases and trans-sialidases play important roles in the life cycles of
      various microorganisms. These enzymes can serve nutritional purposes, act as
      virulence factors or mediate cellular interactions (cell evasion and invasion).
      In the case of the protozoan parasite Trypanosoma vivax, trans-sialidase activity
      has been suggested to be involved in infection-associated anaemia, which is the
      major pathology in the disease nagana. The physiological role of trypanosomal
      trans-sialidases in host-parasite interaction as well as their structures remain
      obscure. Here, the production, purification and crystallization of a recombinant
      version of T. vivax trans-sialidase 1 (rTvTS1) are described. The obtained rTvTS1
      crystals diffracted to a resolution of 2.5 A and belonged to the orthorhombic
      space group P212121, with unit-cell parameters a = 57.3, b = 78.4, c = 209.0 A.

PMID- 25945713
TI  - Identification and structure solution of fragment hits against kinetoplastid N
      myristoyltransferase.
AB  - Trypanosoma brucei N-myristoyltransferase (TbNMT) is an attractive therapeutic
      target for the treatment of human African trypanosomiasis. Pyrazole sulfonamide
      (DDD85646), a potent inhibitor of TbNMT, has been identified in previous studies;
      however, poor central nervous system exposure restricts its use to the
      haemolymphatic form (stage 1) of the disease. In order to identify new chemical
      matter, a fragment screen was carried out by ligand-observed NMR spectroscopy,
      identifying hits that occupy the DDD85646 binding site. Crystal structures of
      hits from this assay have been obtained in complex with the closely related NMT
      from Leishmania major, providing a structural starting point for the evolution of
      novel chemical matter. 

PMID- 25945714
TI  - Structure of an ADP-ribosylation factor, ARF1, from Entamoeba histolytica bound
      to Mg(2+)-GDP.
AB  - Entamoeba histolytica is the etiological agent of amebiasis, a diarrheal disease
      which causes amoebic liver abscesses and amoebic colitis. Approximately 50
      million people are infected worldwide with E. histolytica. With only 10% of
      infected people developing symptomatic amebiasis, there are still an estimated
      100,000 deaths each year. Because of the emergence of resistant strains of the
      parasite, it is necessary to find a treatment which would be a proper response to
      this challenge. ADP-ribosylation factor (ARF) is a member of the ARF family of
      GTP-binding proteins. These proteins are ubiquitous in eukaryotic cells; they
      generally associate with cell membranes and regulate vesicular traffic and
      intracellular signalling. The crystal structure of ARF1 from E. histolytica has
      been determined bound to magnesium and GDP at 1.8 A resolution. Comparison with
      other structures of eukaryotic ARF proteins shows a highly conserved structure
      and supports the interswitch toggle mechanism of communicating the conformational
      state to partner proteins.

PMID- 25945715
TI  - Structure of Plasmodium falciparum orotate phosphoribosyltransferase with
      autologous inhibitory protein-protein interactions.
AB  - The most severe form of malaria is caused by the obligate parasite Plasmodium
      falciparum. Orotate phosphoribosyltransferase (OPRTase) is the fifth enzyme in
      the de novo pyrimidine-synthesis pathway in the parasite, which lacks salvage
      pathways. Among all of the malaria de novo pyrimidine-biosynthesis enzymes, the
      structure of P. falciparum OPRTase (PfOPRTase) was the only one unavailable until
      now. PfOPRTase that could be crystallized was obtained after some low-complexity
      sequences were removed. Four catalytic dimers were seen in the asymmetic unit (a
      total of eight polypeptides). In addition to revealing unique amino acids in the
      PfOPRTase active sites, asymmetric dimers in the larger structure pointed to
      novel parasite-specific protein-protein interactions that occlude the catalytic
      active sites. The latter could potentially modulate PfOPRTase activity in
      parasites and possibly provide new insights for blocking PfOPRTase functions. 

PMID- 25945716
TI  - Structures of prostaglandin F synthase from the protozoa Leishmania major and
      Trypanosoma cruzi with NADP.
AB  - The crystal structures of prostaglandin F synthase (PGF) from both Leishmania
      major and Trypanosoma cruzi with and without their cofactor NADP have been
      determined to resolutions of 2.6 A for T. cruzi PGF, 1.25 A for T. cruzi PGF with
      NADP, 1.6 A for L. major PGF and 1.8 A for L. major PGF with NADP. These
      structures were determined by molecular replacement to a final R factor of less
      than 18.6% (Rfree of less than 22.9%). PGF in the infectious protozoa L. major
      and T. cruzi is a potential therapeutic target.

PMID- 25945717
TI  - Temporoparietal fascial flap repair of middle cranial fossa tegmen and dural
      defects.

PMID- 25945718
TI  - Kinetics and Immunodominance of Virus-Specific T Cell Responses During Hantaan
      Virus Infection.
AB  - Immunodominant T cell responses are important for protection against virus
      challenge. However, studies screening for the immunodominant T cell responses and
      following their kinetics in acute Hantaan virus (HTNV) infection are very
      limited. Herein, the HTNV nucleocapsid protein-specific T cell responses were
      longitudinally screened in 15 patients with acute HTNV infection, eight of whom
      had a particularly severe hemorrhagic fever with renal syndrome (HFRS). An
      extremely impaired IFN-gamma-producing T cell response was observed in patients
      with severe HFRS at the early stage of infection, especially to the
      immunodominant epitopes detected in the mild to moderate group, namely peptides
      N127-141, N139-153, N241-255, and N355-369. The initially insufficient T cell
      response to the immunodominant epitopes may play a role in influencing the
      severity of HTNV infection. These findings provide information that may aid the
      design of future vaccines against hantaviruses. 

PMID- 25945719
TI  - Assessment of drug delivery devices.
AB  - For critical drug delivery, it is important to have a constant and well-known
      infusion rate delivered by the complete infusion set-up (pump, tubing, and
      accessories). Therefore, various drug delivery devices and accessories were
      tested in this article in terms of their infusion accuracy, start-up delay,
      response time, and dependency on the viscosity. These measurements were performed
      as part of the European funded research project MeDD. The obtained results show
      that the infusion accuracy of the devices is flow rate and accessory depended,
      especially for low flow rates. Viscosity does not have a significant impact on
      the flow rate accuracy. 

PMID- 25945720
TI  - Thrombin generation, D-dimer and protein S in uncomplicated pregnancy.
AB  - BACKGROUND: Gestational age-specific reference values are essential for the
      accurate interpretation of haemostatic tests during pregnancy. METHODS: Our 1
      year prospective study included 40 healthy pregnant women with a median age of 30
      (range 22-40) years; the subjects were followed in order to establish the
      gestational age dependent values for endogenous thrombin potential (ETP), D-dimer
      and protein S (activity and free). RESULTS: During the first trimester 50% of
      studied women had ETP >100% (reference values out of pregnancy); in the second
      trimester an ETP over 100% was observed in all women; ETP values remained
      unchanged during the third trimester. In the first trimester, the median D-dimer
      concentration of 0.30 mg/L, in the second 0.91 mg/L and in the third of 1.45 mg/L
      were observed. During the first trimester 14/40 subjects had protein S activity
      below reference range (<59%, out of pregnancy); the median value of 61.35;
      interquartile range (IQR) 20.38; in the second 21/37; the median value of 53.1
      (IQR 15.65); in the third trimester 28/37 had low level of protein S activity
      with the median value of 49.0 (IQR 18.8). Free protein S showed a slight decrease
      from the first trimester; it remained almost stable during the rest of pregnancy,
      with the equal number of pregnant women with reduced free protein S. CONCLUSIONS:
      Related to the gestational age, a significant increase of ETP and D-dimer, from
      the second trimester was observed; the decrease of protein S was observed already
      from the early pregnancy, with more pronounced variability of protein S activity.

PMID- 25945721
TI  - Automated alkaline-pH electrophoresis followed by densitometry does not correlate
      with cation-exchange (CE)-HPLC in quantification of HbA2 and variant hemoglobins.

PMID- 25945722
TI  - Comparison study of two commercially available methods for the determination of
      golimumab and anti-golimumab antibody levels in patients with rheumatic diseases.

PMID- 25945724
TI  - Tuberculous Epididymitis.

PMID- 25945723
TI  - Liver X receptors as regulators of metabolism.
AB  - The liver X receptors (LXR) are crucial regulators of metabolism. After ligand
      binding, they regulate gene transcription and thereby mediate changes in
      metabolic pathways. Modulation of LXR and their downstream targets has appeared
      to be a promising treatment for metabolic diseases especially atherosclerosis and
      cholesterol metabolism. However, the complexity of LXR action in various
      metabolic tissues and the liver side effect of LXR activation have slowed down
      the interest for LXR drugs. In this review, we summarized the role of LXR in the
      main metabolically active tissues with a special focus on obesity and associated
      diseases in mammals. We will also discuss the dual interplay between the two LXR
      isoforms suggesting that they may collaborate to establish a fine and efficient
      system for the maintenance of metabolism homeostasis. 

PMID- 25945725
TI  - Sonographic distinction between acute suppurative appendicitis and viral
      appendiceal lymphoid hyperplasia ("pink appendix") with pathological correlation.
AB  - The viral etiology of mesenteric lymphadenitis may also affect the lymphoid
      tissue of the appendix in children giving rise to symptomatic appendiceal
      lymphoid hyperplasia, the so-called "pink appendix." The present study used
      ultrasound (US) to determine if certain sonographic features correlated with
      appendiceal pathological findings. Our results indicate that a fluid-filled
      appendix always correlates with a suppurative or mixed pathological appearance
      that likely merits surgery. A lymphoid predominant pathological appearance
      occurred only in cases where appendiceal wall thickening alone was seen on US.
      This pilot project therefore shows that US has the potential to stratify acute
      appendix patients into different treatment regimens, given that lymphoid
      hyperplasia could be treated conservatively. Further studies correlating other
      clinicoradiological parameters with this sonographic appearance are warranted. 

PMID- 25945726
TI  - Identify Before Orchiectomy: Segmental Testicular Infarct.

PMID- 25945729
TI  - Reactivity Studies on a Binuclear Ruthenium(0) Complex Equipped with a Bridging
      kappa(2)N,Ge-Amidinatogermylene Ligand.
AB  - The amidinatogermylene-bridged diruthenium(0) complex [Ru2{MU-kappa(2)Ge,N
      Ge((i)Pr2bzam)(HMDS)}(CO)7] (2; (i)Pr2bzam = N,N'-bis(iso-propyl)benzamidinate;
      HMDS = N(SiMe3)2) reacted at room temperature with (t)BuNC and PMe3 to give
      [Ru2{MU-kappa(2)Ge,N-Ge((i)Pr2bzam)(HMDS)}(L)(CO)6] (L = (t)BuNC, 3; PMe3, 4),
      which contain the new ligand in an axial position on the Ru atom that is not
      attached to the amidinato fragment. At 70  degrees C, 2 reacted with PPh3, PMe3,
      dppm, and dppe to give the equatorially substituted derivatives [Ru2{MU
      kappa(2)Ge,N-Ge((i)Pr2bzam)(HMDS)}(L)(CO)6] (L = PPh3, 5; PMe3, 6) and [Ru2{MU
      kappa(2)Ge,N-Ge((i)Pr2bzam)(HMDS)}(MU-kappa(2)P,P'-L2)(CO)5] (L2 = dppm, 7; dppe,
      8). HSiEt3 and HSnPh3 were oxidatively added to complex 2 at 70  degrees C,
      leading to the coordinatively unsaturated products [Ru2(ER3)(MU-H){MU
      kappa(2)Ge,N-Ge((i)Pr2bzam)(HMDS)}(CO)5] (ER3 = SiEt3, 9; SnPh3, 10), which
      easily reacted with (t)BuNC and CO to give the saturated derivatives [Ru2(ER3)(MU
      H){MU-kappa(2)Ge,N-Ge((i)Pr2bzam)(HMDS)}((t)BuNC)(CO)5] (ER3 = SiEt3, 11; SnPh3,
      12) and [Ru2(ER3)(MU-H){MU-kappa(2)Ge,N-Ge((i)Pr2bzam)(HMDS)}(CO)6] (ER3 = SiEt3,
      13; SnPh3, 14), respectively. Compounds 9-14 have their ER3 group on the Ru atom
      that is not attached to the amidinato fragment. In contrast, the reaction of 2
      with H2 at 70  degrees C led to the unsaturated tetranuclear complex [Ru4(MU
      H)2{MU-kappa(2)Ge,N-Ge((i)Pr2bzam)(HMDS)}2(CO)10] (15), which also reacted with
      (t)BuNC and CO to give the saturated derivatives [Ru4(MU-H)2{MU-kappa(2)Ge,N
      Ge((i)Pr2bzam)(HMDS)}2(L)2(CO)10] (L = (t)BuNC, 16; CO, 17). All tetraruthenium
      complexes contain an unbridged metal-metal connecting two germylene-bridged
      diruthenium units. Under CO atmosphere, complex 17 reverted to compound 2. All of
      the coordinatively unsaturated products (9, 10, and 15) have their
      unsaturation(s) located on the Ru atom(s) that is(are) attached to the amidinato
      fragment(s). In the absence of added reagents, the thermolysis of 2 in refluxing
      toluene led to [Ru4{MU-kappa(2)Ge,N-Ge((i)Pr2bzam)(HMDS)}{MU3-kappaGe
      Ge(HMDS)}(MU-kappa(3)N,C,N'-(i)Pr2bzam)(MU-CO)(CO)8] (18), which contains two new
      ligands, a triply bridging germylidyne and a bridging benzamidinate, and that
      results from the condensation of two molecules of 2 and the activation of the Ge
      N bond of the benzamidinatogermylene ligand of 2. 

PMID- 25945727
TI  - Targeted Delivery of LXR Agonist Using a Site-Specific Antibody-Drug Conjugate.
AB  - Liver X receptor (LXR) agonists have been explored as potential treatments for
      atherosclerosis and other diseases based on their ability to induce reverse
      cholesterol transport and suppress inflammation. However, this therapeutic
      potential has been hindered by on-target adverse effects in the liver mediated by
      excessive lipogenesis. Herein, we report a novel site-specific antibody-drug
      conjugate (ADC) that selectively delivers a LXR agonist to monocytes/macrophages
      while sparing hepatocytes. The unnatural amino acid para-acetylphenylalanine
      (pAcF) was site-specifically incorporated into anti-CD11a IgG, which binds the
      alpha-chain component of the lymphocyte function-associated antigen 1 (LFA-1)
      expressed on nearly all monocytes and macrophages. An aminooxy-modified LXR
      agonist was conjugated to anti-CD11a IgG through a stable, cathepsin B cleavable
      oxime linkage to afford a chemically defined ADC. The anti-CD11a IgG-LXR agonist
      ADC induced LXR activation specifically in human THP-1 monocyte/macrophage cells
      in vitro (EC50-27 nM), but had no significant effect in hepatocytes, indicating
      that payload delivery is CD11a-mediated. Moreover, the ADC exhibited higher-fold
      activation compared to a conventional synthetic LXR agonist T0901317 (Tularik) (3
      fold). This novel ADC represents a fundamentally different strategy that uses
      tissue targeting to overcome the limitations of LXR agonists for potential use in
      treating atherosclerosis. 

PMID- 25945730
TI  - Differential Targeting of Human Topoisomerase II Isoforms with Small Molecules.
AB  - The TOP2 poison etoposide has been implicated in the generation of secondary
      malignancies during cancer treatment. Structural similarities between TOP2
      isoforms challenge the rational design of isoform-specific poisons to further
      delineate these processes. Herein, we describe the synthesis and biological
      evaluation of a focused library of etoposide analogues, with the identification
      of two novel small molecules exhibiting TOP2B-dependent toxicity. Our findings
      pave the way toward studying isoform-specific cellular processes by means of
      small molecule intervention. 

PMID- 25945733
TI  - Enhance Cancer Cell Recognition and Overcome Drug Resistance Using Hyaluronic
      Acid and alpha-Tocopheryl Succinate Based Multifunctional Nanoparticles.
AB  - Multidrug resistance (MDR) presents a clinical obstacle to cancer chemotherapy.
      The main purpose of this study was to evaluate the potential of a hyaluronic acid
      (HA) and alpha-tocopheryl succinate (alpha-TOS) based nanoparticle to enhance
      cancer cell recognition and overcome MDR, and to explore the underlying
      mechanisms. A multifunctional nanoparticle, HTTP-50 NP, consisted of HA-alpha-TOS
      (HT) conjugate and d-alpha-tocopheryl polyethylene glycol succinate (TPGS) with
      docetaxel loaded in its hydrophobic core. The promoted tumor cell recognition and
      accumulation, cytotoxicity, and mitochondria-specific apoptotic pathways for the
      HTTP-50 NP were confirmed in MCF-7/Adr cells (P-gp-overexpressing cancer model),
      indicating that the formulated DTX and the conjugated alpha-TOS in the HTTP-50 NP
      could synergistically circumvent the acquired and intrinsic MDR in MCF-7/Adr
      cells. In vivo investigation on the MCF-7/Adr xenografted nude mice models
      confirmed that HTTP-50 NP possessed much higher tumor tissue accumulation and
      exhibited pronouncedly enhanced antiresistance tumor efficacy with reduced
      systemic toxicity compared with HTTP-0 NP and Taxotere. The mechanisms of the
      multifunctional HTTP-50 NP to overcome MDR and enhance antiresistance efficacy
      may be contributed by CD44 receptor-targeted delivery and P-gp efflux inhibition,
      and meanwhile to maximize antitumor efficacy by synergism of DTX and mitocan of
      alpha-TOS killing tumor cells. 

PMID- 25945734
TI  - Erbb4 Signaling: an overlooked backup system?

PMID- 25945735
TI  - Effect of fruits and vegetables on metabolic syndrome: a systematic review and
      meta-analysis of randomized controlled trials.
AB  - Evidence regarding the effect of fruit and vegetable consumption on metabolic
      syndrome remains inconclusive. Using MEDLINE, EMBASE, and Cochrane, we searched
      for relevant studies published before 10 December 2013. Of the 383 articles
      identified, eight randomized controlled trials with 396 participants (205 in
      intervention groups and 191 in control groups) were included in the final
      analyses. Fruit and vegetable intake was associated with a reduction in diastolic
      blood pressure (standardized mean difference: -0.29; 95% confidence interval: 
      0.57 to -0.02; p = 0.04); however, such intake did not affect waist
      circumference, systolic blood pressure, fasting glucose, high-density lipoprotein
      cholesterol, and triglyceride levels in metabolic syndrome patients. In a
      subgroup analysis, there were no statistically significant differences found
      according to the intervention period and provision type. Our results suggest an
      inverse association between fruit and vegetable consumption and diastolic blood
      pressure in metabolic syndrome patients. 

PMID- 25945736
TI  - Associations between dairy products consumption and risk of type 2 diabetes:
      Tehran lipid and glucose study.
AB  - We aimed to examine the relationship between total dairy and dairy subtypes with
      the risk of type 2 diabetes (T2DM) in an Asian population. A nested case-control
      study of 178 cases of incident T2DM and 520 matched controls was conducted within
      the Tehran lipid and glucose study (TLGS). A 27% lower risk of T2DM was found per
      100 g/d total dairy consumption that tend to be significant (95% CI: 0.52-1.02).
      Milk intake was inversely associated with diabetes after adjustment for
      confounders (p-trend: 0.042). Milk intake was associated with decreased T2DM risk
      in men (p-trend: 0.025), but not in women (p-trend: 0.527). Each 100 g/d increase
      in milk intake corresponded to 41% lower T2DM risk in fully adjusted model (95%
      CI: 0.39-0.89) in men. In conclusion, there is no significant association between
      diabetes and total dairy intake in the present study, but high intake of milk may
      reduce T2DM risk among men. 

PMID- 25945737
TI  - An alternative pluripotent state confers interspecies chimaeric competency.
AB  - Pluripotency, the ability to generate any cell type of the body, is an evanescent
      attribute of embryonic cells. Transitory pluripotent cells can be captured at
      different time points during embryogenesis and maintained as embryonic stem cells
      or epiblast stem cells in culture. Since ontogenesis is a dynamic process in both
      space and time, it seems counterintuitive that these two temporal states
      represent the full spectrum of organismal pluripotency. Here we show that by
      modulating culture parameters, a stem-cell type with unique spatial
      characteristics and distinct molecular and functional features, designated as
      region-selective pluripotent stem cells (rsPSCs), can be efficiently obtained
      from mouse embryos and primate pluripotent stem cells, including humans. The ease
      of culturing and editing the genome of human rsPSCs offers advantages for
      regenerative medicine applications. The unique ability of human rsPSCs to
      generate post-implantation interspecies chimaeric embryos may facilitate our
      understanding of early human development and evolution. 

PMID- 25945738
TI  - Coordinated regulation of bidirectional COPI transport at the Golgi by CDC42.
AB  - The Golgi complex has a central role in the intracellular sorting of secretory
      proteins. Anterograde transport through the Golgi has been explained by the
      movement of Golgi cisternae, known as cisternal maturation. Because this
      explanation is now appreciated to be incomplete, interest has developed in
      understanding tubules that connect the Golgi cisternae. Here we show that the
      coat protein I (COPI) complex sorts anterograde cargoes into these tubules in
      human cells. Moreover, the small GTPase CDC42 regulates bidirectional Golgi
      transport by targeting the dual functions of COPI in cargo sorting and carrier
      formation. CDC42 also directly imparts membrane curvature to promote COPI tubule
      formation. Our findings further reveal that COPI tubular transport complements
      cisternal maturation in explaining how anterograde Golgi transport is achieved,
      and that bidirectional COPI transport is modulated by environmental cues through
      CDC42. 

PMID- 25945740
TI  - Evolution: Steps on the road to eukaryotes.

PMID- 25945741
TI  - Cyclic di-GMP acts as a cell cycle oscillator to drive chromosome replication.
AB  - Fundamental to all living organisms is the capacity to coordinate cell division
      and cell differentiation to generate appropriate numbers of specialized cells.
      Whereas eukaryotes use cyclins and cyclin-dependent kinases to balance division
      with cell fate decisions, equivalent regulatory systems have not been described
      in bacteria. Moreover, the mechanisms used by bacteria to tune division in line
      with developmental programs are poorly understood. Here we show that Caulobacter
      crescentus, a bacterium with an asymmetric division cycle, uses oscillating
      levels of the second messenger cyclic diguanylate (c-di-GMP) to drive its cell
      cycle. We demonstrate that c-di-GMP directly binds to the essential cell cycle
      kinase CckA to inhibit kinase activity and stimulate phosphatase activity. An
      upshift of c-di-GMP during the G1-S transition switches CckA from the kinase to
      the phosphatase mode, thereby allowing replication initiation and cell cycle
      progression. Finally, we show that during division, c-di-GMP imposes spatial
      control on CckA to install the replication asymmetry of future daughter cells.
      These studies reveal c-di-GMP to be a cyclin-like molecule in bacteria that
      coordinates chromosome replication with cell morphogenesis in Caulobacter. The
      observation that c-di-GMP-mediated control is conserved in the plant pathogen
      Agrobacterium tumefaciens suggests a general mechanism through which this global
      regulator of bacterial virulence and persistence coordinates behaviour and cell
      proliferation. 

PMID- 25945739
TI  - Complex archaea that bridge the gap between prokaryotes and eukaryotes.
AB  - The origin of the eukaryotic cell remains one of the most contentious puzzles in
      modern biology. Recent studies have provided support for the emergence of the
      eukaryotic host cell from within the archaeal domain of life, but the identity
      and nature of the putative archaeal ancestor remain a subject of debate. Here we
      describe the discovery of 'Lokiarchaeota', a novel candidate archaeal phylum,
      which forms a monophyletic group with eukaryotes in phylogenomic analyses, and
      whose genomes encode an expanded repertoire of eukaryotic signature proteins that
      are suggestive of sophisticated membrane remodelling capabilities. Our results
      provide strong support for hypotheses in which the eukaryotic host evolved from a
      bona fide archaeon, and demonstrate that many components that underpin eukaryote
      specific features were already present in that ancestor. This provided the host
      with a rich genomic 'starter-kit' to support the increase in the cellular and
      genomic complexity that is characteristic of eukaryotes. 

PMID- 25945743
TI  - Identifying an essential role of nuclear LC3 for autophagy.
AB  - MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3), a mammalian
      ortholog of yeast Atg8, is a key protein contributing to major steps of
      autophagy. It has been recognized for a long time that LC3 is abundant in the
      nucleus despite the fact that it functions primarily in the cytoplasm where the
      autophagosomes and autolysosomes arise. An important question regarding nuclear
      LC3 is whether and how it participates in autophagy. In this punctum, we discuss
      our recent findings about the essential role for nuclear LC3 in starvation
      induced autophagy. During nutrient-rich conditions, LC3 is distributed in an
      acetylated form in both the nucleus and cytoplasm. Nutrient deprivation promotes
      the redistribution of LC3 from the nucleus to the cytoplasm. This relocation
      depends on a deacetylation of the protein by the activated nuclear deacetylase
      SIRT1 and the association of the protein with its nuclear interaction partner
      TP53INP2/DOR. More importantly, the deacetylation is also required for LC3 to
      bind with ATG7 for its subsequent lipidation. Therefore, the results implicate
      the nuclear pool of LC3 as the primary source of membrane-conjugated LC3, and a
      regulation of deacetylation and nucleocytoplasmic translocation of LC3 in priming
      starved cells for autophagy induction. 

PMID- 25945742
TI  - Cell biology: Polarized transport in the Golgi apparatus.

PMID- 25945744
TI  - Alanyl-glutamine attenuates 5-fluorouracil-induced intestinal mucositis in
      apolipoprotein E-deficient mice.
AB  - Apolipoprotein E (APOE=gene, apoE=protein) is a known factor regulating the
      inflammatory response that may have regenerative effects during tissue recovery
      from injury. We investigated whether apoE deficiency reduces the healing effect
      of alanyl-glutamine (Ala-Gln) treatment, a recognized gut-trophic nutrient,
      during tissue recovery after 5-FU-induced intestinal mucositis. APOE-knockout
      (APOE-/-) and wild-type (APOE+/+) C57BL6J male and female mice (N=86) were given
      either Ala-Gln (100 mM) or phosphate buffered saline (PBS) by gavage 3 days
      before and 5 days after a 5-fluorouracil (5-FU) challenge (450 mg/kg, via
      intraperitoneal injection). Mouse body weight was monitored daily. The 5-FU
      cytotoxic effect was evaluated by leukometry. Intestinal villus height,
      villus/crypt ratio, and villin expression were monitored to assess recovery of
      the intestinal absorptive surface area. Crypt length, mitotic, apoptotic, and
      necrotic crypt indexes, and quantitative real-time PCR for insulin-like growth
      factor-1 (IGF-1) and B-cell lymphoma 2 (Bcl-2) intestinal mRNA transcripts were
      used to evaluate intestinal epithelial cell turnover. 5-FU challenge caused
      significant weight loss and leukopenia (P<0.001) in both mouse strains, which was
      not improved by Ala-Gln. Villus blunting, crypt hyperplasia, and reduced
      villus/crypt ratio (P<0.05) were found in all 5-FU-challenged mice but not in PBS
      controls. Ala-Gln improved villus/crypt ratio, crypt length and mitotic index in
      all challenged mice, compared with PBS controls. Ala-Gln improved villus height
      only in APOE-/- mice. Crypt cell apoptosis and necrotic scores were increased in
      all mice challenged by 5-FU, compared with untreated controls. Those scores were
      significantly lower in Ala-Gln-treated APOE+/+ mice than in controls. Bcl-2 and
      IGF-1 mRNA transcripts were reduced only in the APOE-/- -challenged mice.
      Altogether our findings suggest APOE-independent Ala-Gln regenerative effects
      after 5-FU challenge.

PMID- 25945745
TI  - DNA methylation patterns of candidate genes regulated by thymine DNA glycosylase
      in patients with TP53 germline mutations.
AB  - Li-Fraumeni syndrome (LFS) is a rare, autosomal dominant, hereditary cancer
      predisposition disorder. In Brazil, the p.R337H TP53 founder mutation causes the
      variant form of LFS, Li-Fraumeni-like syndrome. The occurrence of cancer and age
      of disease onset are known to vary, even in patients carrying the same mutation,
      and several mechanisms such as genetic and epigenetic alterations may be involved
      in this variability. However, the extent of involvement of such events has not
      been clarified. It is well established that p53 regulates several pathways,
      including the thymine DNA glycosylase (TDG) pathway, which regulates the DNA
      methylation of several genes. This study aimed to identify the DNA methylation
      pattern of genes potentially related to the TDG pathway (CDKN2A, FOXA1, HOXD8,
      OCT4, SOX2, and SOX17) in 30 patients with germline TP53 mutations, 10 patients
      with wild-type TP53, and 10 healthy individuals. We also evaluated TDG expression
      in patients with adrenocortical tumors (ADR) with and without the p.R337H TP53
      mutation. Gene methylation patterns of peripheral blood DNA samples assessed by
      pyrosequencing revealed no significant differences between the three groups.
      However, increased TDG expression was observed by quantitative reverse
      transcription PCR in p.R337H carriers with ADR. Considering the rarity of this
      phenotype and the relevance of these findings, further studies using a larger
      sample set are necessary to confirm our results. 

PMID- 25945746
TI  - Hydrogen sulfide in posthemorrhagic shock mesenteric lymph drainage alleviates
      kidney injury in rats.
AB  - Posthemorrhagic shock mesenteric lymph (PHSML) is a key factor in multiple organ
      injury following hemorrhagic shock. We investigated the role of hydrogen sulfide
      (H2S) in PHSML drainage in alleviating acute kidney injury (AKI) by administering
      D,L-propargylglycine (PPG) and sodium hydrosulfide hydrate (NaHS) to 12 specific
      pathogen-free male Wistar rats with PHSML drainage. A hemorrhagic shock model was
      established in 4 experimental groups: shock, shock+drainage, shock+drainage+PPG
      (45 mg/kg, 0.5 h prehemorrhage), and shock+drainage+NaHS (28 umol/kg, 0.5 h
      prehemorrhage). Fluid resuscitation was performed after 1 h of hypotension, and
      PHMSL was drained in the last three groups for 3 h after resuscitation. Renal
      function and histomorphology were assessed along with levels of H2S,
      cystathionine-gamma-lyase (CSE), Toll-like receptor 4 (TLR4), interleukin (IL)
      10, IL-12, and tumor necrosis factor (TNF)-alpha in renal tissue. Hemorrhagic
      shock induced AKI with increased urea and creatinine levels in plasma and higher
      H2S, CSE, TLR4, IL-10, IL-12, and TNF-alpha levels in renal tissue. PHSML
      drainage significantly reduced urea, creatinine, H2S, CSE, and TNF-alpha but not
      TLR4, IL-10, or IL-12. PPG decreased creatinine, H2S, IL-10, and TNF-alpha
      levels, but this effect was reversed by NaHS administration. In conclusion, PHSML
      drainage alleviated AKI following hemorrhagic shock by preventing increases in
      H2S and H2S-mediated inflammation. 

PMID- 25945747
TI  - Synthesis, structure, antimycobacterial and anticancer evaluation of new pyrrolo
      phenanthroline derivatives.
AB  - A study concerning design, synthesis, structure and in vitro antimycobacterial
      and anticancer evaluation of new fused derivatives with pyrrolo[2,1
      c][4,7]phenanthroline skeleton is described. The strategy adopted for synthesis
      involves a [3 + 2] dipolar cycloaddition of several in situ generated 4,7
      phenanthrolin-4-ium ylides to different substituted alkynes and alkenes. Stereo-
      and regiochemistry of cycloaddition reactions were discussed. The structure of
      the new compounds was proven unambiguously, single-crystal X-ray diffraction
      studies including. The antimycobacterial and anticancer activity of a selection
      of new synthesized compounds was evaluated against Mycobacterium tuberculosis
      H37Rv under aerobic conditions and 60 human tumour cell line panel, respectively.
      Five of the tested compounds possess a moderate antimycobacterial activity, while
      two of the compounds have a significant antitumor activity against renal cancer
      and breast cancer.

PMID- 25945748
TI  - In silico modeling of beta-carbonic anhydrase inhibitors from the fungus
      Malassezia globosa as antidandruff agents.
AB  - A quantitative structure-activity relationship (QSAR) study of sulfonamide
      inhibitors targeting the beta-carbonic anhydrase (CA, EC 4.2.1.1) from the fungus
      Malassezia globosa is reported. A large set of PRECLAV descriptors has been used
      to obtain four parametric models. This study presents QSAR data on a pool of 28
      compounds. The quality of prediction is high enough (SE = 0.3446, r(2) = 0.8687,
      F = 39.6921, Q = 0.7446). A heuristic algorithm selected the best multiple linear
      regression (MLR) equation which showed the correlation between the observed
      values and the calculated values of activity. The proposed prediction set
      included new, not yet synthesized, 23 molecules having various structures. Many
      compounds in the prediction set seem to possess higher computed activity compared
      to the presently available M. globosa beta-CA inhibitors. 

PMID- 25945749
TI  - Numerical study on the partitioning of the molecular polarizability into
      fluctuating charge and induced atomic dipole contributions.
AB  - In order to carry out a detailed analysis of the molecular static polarizability,
      which is the response of the molecule to a uniform external electric field, the
      molecular polarizability was computed using the finite-difference method for 21
      small molecules, using density functional theory. Within nine charge population
      schemes (Lowdin, Mulliken, Becke, Hirshfeld, CM5, Hirshfeld-I, NPA, CHELPG, MK
      ESP) in common use, the charge fluctuation contribution is found to dominate the
      molecular polarizability, with its ratio ranging from 59.9% with the Hirshfeld or
      CM5 scheme to 96.2% with the Mulliken scheme. The Hirshfeld-I scheme is also used
      to compute the other contribution to the molecular polarizability coming from the
      induced atomic dipoles, and the atomic polarizabilities in eight small molecules
      and water pentamer are found to be highly anisotropic for most atoms. Overall,
      the results suggest that (a) more emphasis probably should be placed on the
      charge fluctuation terms in future polarizable force field development and (b) an
      anisotropic polarizability might be more suitable than an isotropic one in
      polarizable force fields based entirely or partially on the induced atomic
      dipoles. 

PMID- 25945750
TI  - HP1a/KDM4A is involved in the autoregulatory loop of the oncogene gene c-Jun.
AB  - The proto-oncogene c-Jun plays crucial roles in tumorigenesis, and its aberrant
      expression has been implicated in many cancers. Previous studies have shown that
      the c-Jun gene is positively autoregulated by its product. Notably, it has also
      been reported that c-Jun proteins are enriched in its gene body region. However,
      the role of c-Jun proteins in its gene body region has yet to be uncovered. HP1a
      is an evolutionarily conserved heterochromatin-associated protein, which plays an
      essential role in heterochromatin-mediated gene silencing. Interestingly,
      accumulating evidence shows that HP1a is also localized to euchromatic regions to
      positively regulate gene transcription. However, the underlying mechanism has not
      been defined. In this study, we demonstrate that HP1a is involved in the positive
      autoregulatory loop of the Jra gene, the c-Jun homolog in Drosophila. Jra
      recruits the HP1a/KDM4A complex to its gene body region upon osmotic stress to
      reduce H3K36 methylation levels and disrupt H3K36 methylation-dependent histone
      deacetylation, resulting in high levels of histone acetylation in the Jra gene
      body region, thus promoting gene transcription. These results not only expand our
      knowledge toward the mechanism of c-Jun regulation, but also reveal the mechanism
      by which HP1a exerts its positive regulatory function in gene expression. 

PMID- 25945752
TI  - Use of Restrictive Transfusion in Abdominal Surgery: Should Evidence-Based
      Medicine Replace Art of Medicine?

PMID- 25945751
TI  - COCATS 4: Securing the Future of Cardiovascular Medicine.
AB  - The latest iteration of the Core Cardiology Training Statement (COCATS 4)
      [Corrected] provides a potentially transformative advancement in cardiovascular
      fellowship training intended, ultimately, to improve patient care. This review
      addressed 3 primary themes of COCATS 4 from the perspective of fellows-in
      training: 1) the evolution of training requirements culminating in a competency
      based curriculum; 2) the development of novel learning paradigms; and 3) the
      establishment of task forces in emerging areas of multimodality imaging and
      critical care cardiology. This document also examined several important
      challenges presented by COCATS 4. The proposed changes in COCATS 4 should not
      only enhance the training experience but also improve trainee satisfaction.
      Because it embraces continual transformation of training requirements to meet
      evolving clinical needs and public expectations, COCATS 4 will enrich the
      cardiovascular fellowship training experience for patients, programs, and fellows
      in-training.

PMID- 25945753
TI  - Fast-food intake and perceived and objective measures of the local fast-food
      environment in adolescents.
AB  - OBJECTIVE: We examined associations between fast-food intake and perceived and
      objective fast-food outlet exposure. DESIGN: Information from the Health
      Behaviours in School-aged Children Study was linked to fast-food outlets in
      seventy-five school neighbourhoods. We used multivariate multilevel logistic
      regression analyses to examine associations between at least weekly fast-food
      intake and perceived and objective fast-food outlet measures. SUBJECTS: Data
      represent 4642 adolescents (aged 11-15 years) in Denmark. RESULTS: Boys reporting
      two or more fast-food outlets had 34% higher odds consuming fast food at least
      weekly. We detected higher odds of at least weekly fast-food intake among 15-year
      old 9th graders (ORall=1.74; 95% CI 1.40, 2.18; ORboys=2.20; 95% CI 1.66, 2.91;
      ORgirls=1.41; 95% CI 1.03, 1.92), Danish speakers (ORall=2.32; 95% CI 1.68, 3.19;
      ORboys=2.58; 95% CI 1.69, 3.93; ORgirls=2.37; 95% CI 1.46, 3.84) and those
      travelling 15 min or less to school (ORall=1.21; 95% CI 1.00, 1.46; ORgirls=1.44;
      95% CI 1.08, 1.93) compared with 11-year-old 5th graders, non-Danish speakers and
      those with longer travel times. Boys from middle- (OR=1.28; 95% CI 1.00, 1.65)
      and girls from low-income families (OR=1.46; 95% CI 1.05, 2.04) had higher odds
      of at least weekly fast-food intake compared with those from high-income
      backgrounds. Girls attending schools with canteens (OR=1.47; 95% CI 1.00, 2.15)
      had higher odds of at least weekly fast-food intake than girls at schools without
      canteens. CONCLUSIONS: The present study demonstrates that perceived food outlets
      may impact fast-food intake in boys while proximity impacts intake in girls.
      Public health planning could target food environments that emphasize a better
      understanding of how adolescents use local resources.

PMID- 25945755
TI  - Discover and defend the middle ground.

PMID- 25945754
TI  - The peanut butter and jelly sandwich test.

PMID- 25945756
TI  - The pros and cons of third molar extractions.

PMID- 25945757
TI  - Specialist relationships in interdisciplinary dentistry.

PMID- 25945758
TI  - A retrospective study on the use of a dental dressing to reduce dry socket
      incidence in smokers.
AB  - This study assessed the effectiveness of using an oxidized cellulose dental
      dressing in order to reduce the rate of alveolar osteitis after posterior tooth
      extraction in smokers. Dry socket incidences of heavy smokers from 4 independent
      dental clinics, which routinely used oxidized cellulose dental dressings to
      mitigate dry socket formation between March 2011 and December 2012, were compiled
      and evaluated. All extraction sites healed uneventfully except for those cases
      that developed dry sockets. Overall, 1.7% of male patients and 2.2% of female
      patients developed dry sockets. No conclusive relationship was found between the
      number of cigarettes smoked and dry socket formation among patients in this
      study. The results of this study were consistent with the view that gender, age,
      postextraction regimen, and multiple extractions affect dry socket formation. The
      results indicate that an oxidized cellulose dental dressing postextraction is a
      safe and effective method for mitigating dry socket formation among smokers. 

PMID- 25945759
TI  - What every dentist should know about artificial sweeteners and their effects.
AB  - Artificial sweeteners are a ubiquitous commodity on the market. The idea that
      people can consume a sweet food or beverage with "zero" calories seems too good
      to be true, and perhaps it is. The longevity and abundance of these products on
      the market necessitate the study of their mechanisms and their relationships to
      health and disease, including possible links to obesity, cardiovascular disease,
      and diabetes. 

PMID- 25945760
TI  - Kinetics of salivary pH after acidic beverage intake by patients undergoing
      orthodontic treatment.
AB  - The saliva of patients undergoing orthodontic treatment with fixed appliances can
      potentially present a delay in the diluting, clearing, and buffering of dietary
      acids due to an increased number of retention areas. The aim of this clinical
      trial was to compare salivary pH kinetics of patients with and without
      orthodontic treatment, following the intake of an acidic beverage. Twenty
      participants undergoing orthodontic treatment and 20 control counterparts had
      their saliva assessed for flow rate, pH, and buffering capacity. There was no
      significant difference between salivary parameters in participants with or
      without an orthodontic appliance. Salivary pH recovery following acidic beverage
      intake was slower in the orthodontic subjects compared to controls. Patients with
      fixed orthodontic appliances, therefore, seem to be at higher risk of dental
      erosion, suggesting that dietary advice and preventive care need to be
      implemented during orthodontic treatment. 

PMID- 25945761
TI  - Nanoleakage of fiber posts luted with different adhesive strategies and the
      effect of chlorhexidine on the interface of dentin and self-adhesive cements.
AB  - The aim of this in vitro study was to evaluate the nanoleakage of fiber posts
      luted using different adhesive strategies and to investigate the effect of 2%
      chlorhexidine (CHX) on nanoleakage at the resin-dentin interfaces of self
      adhesive cements. The self-adhesive and etch-and-rinse adhesive groups tested
      demonstrated similar results with regard to nanoleakage. Pretreatment with CHX
      promoted an adequate seal at the resin-dentin interface for self-adhesive
      cements. 

PMID- 25945762
TI  - Microcomputed tomography marginal fit evaluation of computer-aided
      design/computer-aided manufacturing crowns with different methods of virtual
      model acquisition.
AB  - This in vitro study used microcomputed tomography to evaluate the marginal fit of
      crowns fabricated using a chairside computer-aided design/computer-aided
      manufacturing (CAD/CAM) system with different methods of virtual model
      acquisition. Crowns were fabricated to fit in a cast containing a single human
      premolar. Four methods of virtual model acquisition were used: Group 1 (control),
      digital impressioning of a typodont; Group 2, digital impressioning of a powdered
      typodont; Group 3, digital impressioning of a regular impression; and Group 4,
      digital impressioning of a master cast. Statistically significant differences
      were found between the marginal gap of Group 2 and the other groups (P < 0.05);
      no differences were found among Groups 1, 3, and 4. The results showed that
      crowns fabricated using the chairside CAD/CAM system exhibited significantly
      smaller vertical misfit when a thin layer of powder was applied over the typodont
      before digital impressioning. 

PMID- 25945764
TI  - Clinical performance of topical sodium fluoride when supplementing carbamide
      peroxide at-home bleaching gel.
AB  - This clinical study evaluated the use of 0.11% topical sodium fluoride (SF)
      desensitizing agent to treat tooth sensitivity during a nightguard tooth
      whitening procedure. Thirty-two subjects bleached their teeth with 10% carbamide
      peroxide (CP) gel using an at-home bleaching technique with custom trays. During
      bleaching treatment, subjects were divided into 2 groups (n = 16). The subjects
      in Group 1 received a topical gel containing 0.11% SF; the subjects in Group 2
      received a placebo gel (PG). Each subject was instructed to place the gel in
      his/her bleaching tray for 30 min every day following bleaching treatment.
      Results showed the use of SF did not affect the whitening efficacy of the 10% CP
      gel. Subjects who received the PG had significantly higher tooth sensitivity when
      compared with subjects who received SF (P < 0.00). The use of daily 0.11% SF
      after 10% CP bleaching gel reduced tooth sensitivity during the bleaching
      treatment. 

PMID- 25945763
TI  - The effect of using propylene glycol as a vehicle on the microhardness of mineral
      trioxide aggregate.
AB  - While it has been proven that the handling properties of mineral trioxide
      aggregate (MTA) are improved upon mixing it with propylene glycol (PG), this
      study sought to evaluate how PG affects the microhardness of MTA in terms of
      setting quality. MTA was mixed with different proportions of distilled water (DW)
      and PG to prepare 5 groups (n = 30). The DW/PG percent proportions used in Groups
      1-5 were 100/0, 80/20, 50/50, 20/80, and 0/100, respectively. The mixed MTA was
      condensed into acrylic molds. Half of the samples of each group were evaluated on
      Day 4, the other half on Day 28. The results indicated that PG reduces the
      microhardness of MTA, thus adversely affecting its setting process. Group 2 (80%
      DW/20% PG) best improved the handling of MTA without a significant reduction in
      setting quality. 

PMID- 25945765
TI  - Physical properties of a new sonically placed composite resin restorative
      material.
AB  - A new nanohybrid composite activated by sonic energy has been recently introduced
      as a single-step, bulk-fill restorative material. The purpose of this study was
      to compare the physical properties of this new composite to various other
      composite restorative materials marketed for posterior or bulk-fill placement.
      The following physical properties were examined: depth of cure, volumetric
      shrinkage, flexural strength, flexural modulus, fracture toughness, and percent
      porosity. A mean and standard deviation were determined per group. One-way ANOVA
      and Tukey's post hoc tests were performed per property (alpha = 0.05). Percent
      porosity was evaluated with a Kruskal-Wallis/Mann-Whitney test (alpha = 0.005).
      Significant differences were found between groups (P < 0.001) per test type.
      Compared to the other composite restorative materials, the new nanohybrid
      composite showed low shrinkage and percent porosity, moderate fracture toughness
      and flexural modulus, and high flexural strength. However, it also demonstrated a
      relatively reduced depth of cure compared to the other composites. 

PMID- 25945766
TI  - Fracture resistance of weakened roots restored with different intracanal
      retainers.
AB  - The purposes of the study were to evaluate the effect of mechanical cycling (MC)
      on the fracture resistance of endodontically treated weakened roots restored with
      different intraradicular retainers and to analyze the failure mode. Eighty bovine
      roots were prepared and restored: 20 roots were reconstructed with cast post-and
      cores (CPCs); 20 with fiber posts (FPs); 20 with fiber posts with larger coronal
      diameter (FPLs); and 20 with anatomic posts (APs). Metal crowns were cemented in
      all the roots. Half of specimens from each restoration strategy (n = 10) were
      submitted to MC: CPC-MC, FP-MC, FPL-MC, and AP-MC. The specimens were subjected
      to a fracture resistance test. The results showed that the type of retainer used
      was statistically significant (P < 0.0004). The CPC specimens demonstrated a
      fracture resistance similar to that of the APs, but greater than that of the FPs
      and FPLs. MC was statistically significant (P < 0.003) and affected AP-MC
      fracture resistance, which was lower than that of CPC-MC and similar to those of
      FP-MC and FPL-MC. 

PMID- 25945767
TI  - Dental management of a patient with Wilson's disease.
AB  - Wilson's disease (WD) is an autosomal recessive genetic disease, characterized by
      the accumulation of copper in the body--primarily in the brain and liver--due to
      defective biliary copper excretion by hepatocytes. WD may manifest clinically as
      liver disease, neurologic symptoms, and Kayser-Fleischer corneal rings. This
      article presents a case involving a 43-year-old man who had WD prior to liver
      transplantation. Oral examination revealed petechiae in the oral mucosa, poor
      oral hygiene, periodontal disease, missing teeth, and several carious teeth.
      Patients with WD may present systemic changes that affect dental care. Dental
      treatment prior to liver transplantation is recommended to eliminate the oral
      foci of infection and control oral disease.

PMID- 25945768
TI  - Endodontic treatment of mandibular molars with atypical root canal anatomy:
      reports of 4 cases.
AB  - The variations in root canal anatomy of multirooted teeth represent a continuous
      challenge to endodontic diagnosis and treatment. Although the most common
      configuration of mandibular molars is one containing 2 roots and 3 root canals,
      there are many different combinations. Very rarely, an additional third
      (supernumerary) root is seen. When it is located distolingually to the main
      distal root, this third root is called radix entomolaris (RE), and when it is
      located mesiobuccally to the mesial root, it is called radix paramolaris (RP).
      Variations of root canal systems need not always be in the form of extra roots or
      extra canals. Single roots with single canals can also occur. A general dentist
      should be aware of these unusual root canal morphologies in mandibular molars for
      the success of endodontic treatment. These case reports describe the root canal
      treatment of a case of RE in the mandibular first molar, 2 rare cases of RP (1
      each in the mandibular first and second molars), and a mandibular second molar
      with a single root and root canal. 

PMID- 25945769
TI  - Hearing loss associated with long-term exposure to high-speed dental handpieces.
AB  - The purpose of this study was to record and compare audiometric pure tone
      thresholds of dental clinicians (DCs), dental professionals (DPs), and dental
      students (DSs); determine the percentage of these groups who use hearing
      protection devices while at work in the clinic; and measure the sound intensities
      generated by a few representative high-speed handpieces while they are being used
      on patients. Participants included DCs who regularly used these handpieces (n =
      16), DPs who did not use these handpieces (n = 13), and DSs (n = 8). A
      questionnaire was used to collect demographic information, assess occupational
      and recreational noise exposure, and note the level of hearing protection used. A
      sound level meter was used to measure the sound intensity generated by dental
      instruments near a clinician's ear. Results showed that DCs who regularly used
      high-speed handpieces had worse hearing than did members of the other study
      groups. These results indicate that the implementation of protective strategies
      should help to reduce the prevalence of occupational hearing loss among DCs. 

PMID- 25945770
TI  - Apical lesion of mandibular bicuspid. Apical lesion of maxillary molar. Cemento
      osseous dysplasia. Cementoblastoma.

PMID- 25945771
TI  - Evaluation of the bond strengths of 3 endodontic cements via push-out test.
AB  - In this study, the push-out method was used to evaluate the bond strengths of 3
      types of endodontic cements according to their composite base: methacrylate,
      epoxy resin, and an experimental copaiba oil resin. The study hypothesis was that
      the methacrylate-based and experimental cements would have bond strengths equal
      to or greater than that of the epoxy resin-based cement. Thirty bovine tooth
      roots, 18 mm long, were divided into 3 groups (n = 10) based on the chosen cement
      treatment. After treatment, the specimens were sectioned and submitted to a push
      out test. Results showed that there was no statistically significant difference
      (P < 0.05) between the cements used or between the middle and apical thirds of
      the roots. It could be concluded that the tested cements had satisfactory and
      similar bond strengths to dentin. 

PMID- 25945772
TI  - Unusual cases of transmigrated mandibular canines.
AB  - Transmigration, an extremely rare anomaly that happens almost exclusively with
      mandibular canines, is defined as a pre-eruptive migration across the midline. It
      can lead to various restorative, surgical, orthodontic, and interceptive
      problems. This condition usually is not related to any painful symptoms and
      cannot be detected on clinical examination. This article presents 3 cases of
      transmigration. In 1 case, the right canine was involved, which is considered to
      be especially rare. This case series also highlights the importance of early
      diagnosis for the interceptive treatment of transmigration. 

PMID- 25945773
TI  - Clinical outcomes of indirect composite restorations for grossly mutilated
      primary molars: a clinical observation.
AB  - This study was conducted to report the clinical outcomes and the parental and
      child satisfaction of onlays for restoring mutilated primary molars. Twenty
      subjects, ages 3-8 years, with the presence of at least 1 mutilated primary molar
      (>=3 carious surfaces and a carious surface area >=3/4 of the occlusal surface)
      were recruited. This study assessed the clinical success, gingival health, and
      parent/child satisfaction of 28 indirect composite onlays. The onlays showed a
      100% retention rate at 12 months follow-up and a marginal integrity of 96.43%.
      High rates of satisfactory Alpha ratings for color stability (92.86%), surface
      texture (92.86%), and anatomic form (100%), coupled with significant improvements
      in gingival health of the restored teeth (P < 0.05), were reported. Indirect
      composite onlays successfully restored anatomic form and function of the grossly
      decayed primary molars--with shorter chairside times--while satisfying the
      esthetic demands of the young pediatric patients.

PMID- 25945774
TI  - Clinicopathological aspects of 25 cases of sialolithiasis of minor salivary
      glands.
AB  - Sialolithiasis of minor salivary glands (SMSG) is rarely reported and presumably
      represents an underestimated disease. This study examined the clinicopathological
      aspects of 25 selected SMSG cases over an 11-year period at the Oral Pathology
      Department of the University of Sao Paulo, Brazil. SMSG was not a clinical
      diagnosis in 92% of the cases. Histologically, the sialoliths tended to be
      superficial and formed by concentric layers with variable degrees of
      mineralization. Chronic periductal and parenchymal inflammation were frequent, as
      well as squamous metaplasia of the affected duct. Ectasia, squamous and mucous
      metaplasia, mucous plug formation, and cellular debris were seen in adjacent
      ducts. Clinicians should be aware of SMSG, especially with regard to its higher
      incidence in the upper lip and buccal mucosa. 

PMID- 25945775
TI  - Oral manifestations in gastroesophageal reflux disease.
AB  - Many systemic diseases exert their influence on oral health. Among these,
      gastroesophageal reflux disease (GERD) is the most common. In this study, 100
      patients who were previously diagnosed with GERD were examined following a 12
      hour fast and evaluated in terms of the severity (grade) of the disease as well
      as any oral, dental, and/or salivary pH changes. Results found 11 patients with
      tooth erosion. These patients were older, and their average mean duration of GERD
      was longer in comparison to those without erosion. There was an inverse
      relationship between salivary pH and the GERD duration and grade of severity. As
      the GERD grade increased, the severity of tooth erosion increased. Patients with
      erosion also exhibited oral mucosal changes. Thus severe, long-term GERD was
      found to be potentially detrimental to oral soft tissues, dental structures, and
      salivary pH, whereas milder forms of the disease did not necessarily cause dental
      side effects. 

PMID- 25945776
TI  - Use of a bite registration vinyl polysiloxane material to identify denture flange
      overextension and/or excessive border thickness in removable prosthodontics.
AB  - Vinyl polysiloxane (VPS) has multiple applications in prosthodontics. This
      article describes how a bite registration fast-set VPS material was used to
      identify length overextension and/or excessive border thickness of denture
      flanges. In addition, the advantages of VPS over conventional materials are
      presented. 

PMID- 25945777
TI  - Low-shrinkage composites: an in vitro evaluation of sealing ability after
      occlusal loading.
AB  - The objective of this in vitro study was to compare the microleakage of a
      flowable low-shrinkage-stress resin composite--in a Class II fatigue-loading
      design when used as a 4 mm dentin replacement--to a conventionally layered
      silorane-based resin composite. Eighty standardized 4 mm deep cavities, divided
      into 4 subgroups, were restored with the 2 tested materials. Half of the
      restorations were submitted to mechanical loading, and all of the restorations
      were prepared for microleakage evaluation. The evaluation of the marginal
      adaptation to dentin was performed with scanning electron microscopy. The results
      showed that both silorane-based composite groups had higher rates of microleakage
      in comparison to the low-shrinkage-stress resin composite groups.

PMID- 25945778
TI  - Management of uncommon complications in seemingly routine oral surgeries.
AB  - Major complications in outpatient oral surgeries are relatively rare. This
      article presents 4 cases of molar extraction with unusual complications and
      describes how the clinician in each case altered the treatment, resulting in a
      successful conclusion. The first case describes a fracture during the removal of
      a maxillary first molar. The second case describes a fracture after a mandibular
      third molar extraction. The third case describes a maxillary third molar
      displaced into the infratemporal space. The final case describes necrosis of the
      maxillary soft tissue after fracture of the tuberosity during a third molar
      extraction. 

PMID- 25945779
TI  - State-Dependent Differences in Emotion Regulation Between Unmedicated Bipolar
      Disorder and Major Depressive Disorder.
AB  - IMPORTANCE: Major depressive disorder (MDD) and bipolar disorder (BD) are
      difficult to distinguish clinically during the depressed or remitted states. Both
      mood disorders are characterized by emotion regulation disturbances; however,
      little is known about emotion regulation differences between MDD and BD. Better
      insight into these differences would be helpful for differentiation based on
      disorder-specific underlying pathophysiological mechanisms. Previous studies
      comparing these disorders often allowed medication use, limiting generalizability
      and validity. Moreover, patients with MDD and BD were mostly compared during the
      depressed, but not the remitted, state, while state might potentially modulate
      differences between MDD and BD. OBJECTIVE: To investigate positive and negative
      emotion regulation in medication-free patients with MDD and BD in 2 mood states:
      depressed or remitted. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study
      conducted from May 2009 to August 2013 comparing behavioral and functional
      magnetic resonance imaging emotion regulation data of 42 patients with MDD, 35
      with BD, and 36 healthy control (HC) participants free of psychotropic medication
      recruited from several psychiatric institutions across the Netherlands.
      INTERVENTION: A voluntary emotion regulation functional magnetic resonance
      imaging task using positive and negative pictures. MAIN OUTCOMES AND MEASURES:
      Behavioral and functional magnetic resonance imaging blood oxygen level-dependent
      responses during emotion regulation. RESULTS: In the remitted state, only
      patients with BD showed impaired emotion regulation (t = 3.39; P < .001; Cohen d
      = 0.70), irrespective of emotion type and associated with increased dorsolateral
      prefrontal cortex activity compared with those with MDD and healthy control
      participants (P = .008). In the depressed state, patients with MDD and BD
      differed with regard to happy vs sad emotion regulation (t = 4.19; P < .001;
      Cohen d = 1.66) associated with differences in rostral anterior cingulate
      activity (P < .001). Patients with MDD regulated sad and happy emotions poorly
      compared with those with BD and healthy control participants, while they
      demonstrated no rostral anterior cingulate difference between happy and sad
      emotion regulation. In contrast, patients with BD performed worse than those with
      MDD on sad emotion regulation but normal on happy emotion regulation, and they
      demonstrated significantly less rostral anterior cingulate activity while
      regulating happy compared with sad emotions. CONCLUSIONS AND RELEVANCE:
      Medication-free patients with MDD vs BD appear to differ in brain activations
      during emotion regulation, both while depressed and in remission. These different
      neuropathophysiological mechanisms between MDD and BD may be useful for further
      development of additional diagnostic tools.

PMID- 25945780
TI  - Shift work and mental health sickness absence: a 10-year observational cohort
      study among male production workers.
AB  - OBJECTIVES: Epidemiological studies investigating mental-health-related sickness
      absence (SA) among shift workers are lacking. This 10-year observational study
      investigated the risk of mental health SA among shift compared with day workers.
      METHODS: The data of 5826 male production workers were used for analyses: 4288
      (74%) shift and 1538 (26%) day workers. The risk of mental health SA was analyzed
      with Cox regression analysis. Hazard ratios (HR) and 95% confidence intervals
      (95% CI) were adjusted for age and occupational grade. RESULTS: During a 10-year
      follow-up, 351 shift workers and 126 day workers had incident mental health SA.
      The risk of mental health SA did not differ (HR 1.03, 95% CI 0.84-1.26) between
      shift and day workers. Among shift workers, the risk of SA due to mood disorders
      (HR 1.87, 95% CI 0.73-4.76) was non-significantly higher than among day workers.
      A total of 96 shift workers and 21 day workers had recurrent mental health SA.
      The risk of recurrent mental health SA did not differ (HR 1.04, 95% CI 0.62-1.74)
      between shift and day workers. CONCLUSION: The risk of incident and recurrent
      mental health SA did not differ between shift and day workers.

PMID- 25945781
TI  - Effects of age on follicular fluid exosomal microRNAs and granulosa cell
      transforming growth factor-beta signalling during follicle development in the
      mare.
AB  - Age-related decline in fertility is a consequence of low oocyte number and/or low
      oocyte competence resulting in pregnancy failure. Transforming growth factor
      (TGF)-beta signalling is a well-studied pathway involved in follicular
      development and ovulation. Recently, small non-coding RNAs, namely microRNAs
      (miRNAs), have been demonstrated to regulate several members of this pathway;
      miRNAs are secreted inside small cell-secreted vesicles called exosomes. The
      overall goal of the present study was to determine whether altered exosome miRNA
      content in follicular fluid from old mares is associated with changes in TGF-beta
      signalling in granulosa cells during follicle development. Follicular fluid was
      collected at deviation (n=6), mid-oestrus (n=6) and preovulation (n=6) for
      identification of exosomal miRNAs from young (3-12 years) and old (20-26 years)
      mares. Analysis of selected TGF-beta signalling members revealed significantly
      increased levels of interleukin 6 (IL6) in granulosa cells from mid-oestrus
      compared with preovulatory follicles, and collagen alpha-2(I) chain (COL1A2) in
      granulosa cells from deviation compared with preovulatory follicles in young
      mares. In addition, granulosa cells from old mares had significantly altered
      levels of DNA-binding protein inhibitor ID-2 (ID2), signal transducer and
      activator of transcription 1 (STAT1) and cell division cycle 25A (CDC25A).
      Finally, changes in exosomal miRNA predicted to target selected TGF-beta members
      were identified. 

PMID- 25945782
TI  - Specificity of the Zn(2+), Cd(2+) and Ni(2+) ion binding sites in the loop domain
      of the HypA protein.
AB  - The zinc binding loop domain of the HypA protein of Helicobacter pylori consists
      of two CXXC motifs with flanking His residues. These motifs bind metal ions, and
      thus they are crucial for the functioning of the whole protein. The N-terminal
      site, where His is separated from CXXC by Ser residue is more effective in
      binding Zn(2+) and Ni(2+) ions than the C-terminal site, in which His is adjacent
      to the CXXC motif. Studies on various modifications of the peptide sequence
      within the Ac-ELECKDCSHVFKPNALDYGVCEKCHS-NH2 loop show the role of the residues
      in the linker between the CXXC motifs and the effect of the length of the linker
      on the stability of the complexes it forms with Zn(2+), Cd(2+) and Ni(2+) ions.
      The proline residue in the linker between the two CXXC binding sites plays a
      distinct role in the metal ion binding ability of the loop, lowering the efficacy
      of the metal ion coordination. The deletion of the aliphatic residues from the
      linker between the CXXC motifs remarkably improves the binding efficacy of the
      loop. 

PMID- 25945783
TI  - Isolation of a novel lutein-protein complex from Chlorella vulgaris and its
      functional properties.
AB  - A novel kind of lutein-protein complex (LPC) was extracted from heterotrophic
      Chlorella vulgaris through aqueous extraction. The purification procedure
      contained solubilization of thylakoid proteins by a zwitterionic detergent CHAPS,
      anion exchange chromatography and gel filtration chromatography. Both wavelength
      scanning and HPLC analysis confirmed that lutein was the major pigment of the
      protein-based complex, and the mass ratio of lutein and protein was determined to
      be 9.72 : 100. Besides showing lipid peroxidation inhibition activity in vitro,
      LPC exerted significant antioxidant effects against ABTS and DPPH radicals with
      IC50 of 2.90 and 97. 23 MUg mL(-1), respectively. Meanwhile, in vivo antioxidant
      activity of the complex was evaluated using the mice hepatotoxicity model; LPC
      significantly suppressed the carbon tetrachloride-induced elevation of serum
      alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities,
      and decreased hepatic malondialdehyde (MDA) levels and the hepatosomatic index.
      Moreover, LPC could effectively restore the activities of superoxide dismutase
      (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in the treated mice
      livers. Our findings further the progress in the research of natural protein
      based lutein complexes, suggesting that LPC has the potential in hepatoprotection
      against chemical induced toxicity and in increasing the antioxidant capacity of
      the defense system in the human body.

PMID- 25945784
TI  - Role of mean platelet volume levels in asthmatic children remains debatable.

PMID- 25945785
TI  - Scoping review of the exclusion and inclusion of rural newcomers in community
      participation.
AB  - Few studies have considered the impact of rural migration on rural community
      engagement. The objective of this research was to undertake a scoping review
      about the inclusion and exclusion of newcomers in rural community participation
      to inform design of inclusive participation processes. The scoping review used
      the six stages of Arksey and O'Malley's methodological framework. Narrative
      analysis of the articles was structured using three themes of inclusion and
      exclusion derived from the literature: interpersonal, socio-cultural norms, and
      structural and organisational processes. Inclusion and exclusion at the
      interpersonal level is intricate and often represents broader social rules and
      tensions that newcomers must navigate in order to become involved. Social norms,
      such as fear of outsiders and difference, can exclude newcomers from
      participating in a rural community. Newcomer's awareness of these issues means
      they are mindful of how they contribute and give respect to the social position
      of existing residents. Despite this, resistance to change is experienced by
      newcomers when contributing in organisational contexts. Formal participation
      processes can harness the practice and value of rural hospitality that newcomers
      experience as inclusionary. Deliberately designing group processes and
      operational norms for inclusion can reduce tensions when change occurs and
      prevent group loss due to exclusionary practices.

PMID- 25945786
TI  - Fisetin Suppresses Lipid Accumulation in Mouse Adipocytic 3T3-L1 Cells by
      Repressing GLUT4-Mediated Glucose Uptake through Inhibition of mTOR-C/EBPalpha
      Signaling.
AB  - 3,7,3',4'-Tetrahydroxyflavone (fisetin) is a flavonoid found in vegetables and
      fruits having broad biological activities. Here the effects of fisetin on
      adipogenesis and its regulatory mechanism in mouse adipocytic 3T3-L1 cells are
      studied. Fisetin inhibited the accumulation of intracellular lipids and lowered
      the expression of adipogenic genes such as peroxisome proliferator-activated
      receptor gamma and CCAAT/enhancer-binding protein (C/EBP) alpha and fatty acid
      binding protein 4 (aP2) during adipogenesis. Moreover, the mRNA levels of genes
      such as acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase
      involved in the fatty acid biosynthesis (lipogenesis) were reduced by the
      treatment with fisetin. The expression level of the glucose transporter 4 (GLUT4)
      gene was also decreased by fisetin, resulting in down-regulation of glucose
      uptake. Furthermore, fisetin inhibited the phosphorylation of the mammalian
      target of rapamycin (mTOR) and that of p70 ribosomal S6 kinase, a target of the
      mTOR complex, the inhibition of which was followed by a decreased mRNA level of
      the C/EBPalpha gene. The results obtained from a chromatin immunoprecipitation
      assay demonstrated that the ability of C/EBPalpha to bind to the GLUT4 gene
      promoter was reduced by the treatment with fisetin, which agreed well with those
      obtained when 3T3-L1 cells were allowed to differentiate into adipocytes in
      medium in the presence of rapamycin, an inhibitor for mTOR. These results
      indicate that fisetin suppressed the accumulation of intracellular lipids by
      inhibiting GLUT4-mediated glucose uptake through inhibition of the mTOR
      C/EBPalpha signaling in 3T3-L1 cells. 

PMID- 25945787
TI  - Peripheral Dendritic Cells and CD4+CD25+Foxp3+ Regulatory T Cells in the First
      Trimester of Normal Pregnancy and in Women with Recurrent Miscarriage.
AB  - The development of pregnancy is possible due to initiation of immune response in
      the body of the mother resulting in immune tolerance. Miscarriage may be caused
      by the impaired maternal immune response to paternal alloantigens located on the
      surface of trophoblast and fetal cells. The aim of the study was to compare the
      population of circulating dendritic cells (DCs) and CD4+CD25+Foxp3+ regulatory T
      cells (TREGs) in the first trimester of a normal pregnancy and in women with
      recurrent miscarriage and an attempt to determine the relationship between these
      cells and the role they may play in human reproductive failures. The study was
      conducted in a group of 33 first trimester pregnant women with recurrent
      miscarriage and in a group of 20 healthy pregnant women in the first trimester of
      normal pregnancy. Among mononuclear cells isolated from peripheral blood, the
      populations of DCs and TREGs were assessed by flow cytometry. The percentage of
      myeloid DCs and lymphoid DCs showed no significant difference between study and
      control group. Older maternal age and obesity significantly reduced the pool of
      circulating myeloid and lymphoid DCs (R=-0.39, p=0.02). In miscarriages the
      percentage of circulating TREGs was significantly lower compared to normal
      pregnancies (p=0.003). Among the analysed factors the percentage of TREGs was the
      most sensitive and the most specific parameter which correlated with the
      pregnancy loss. The reduction in the population of circulating TREGs suggests
      immunoregulatory mechanisms disorder in a pregnancy complicated by miscarriage. 

PMID- 25945788
TI  - Matrix metalloproteinases -8 and -9 and tissue inhibitor of metalloproteinase-1
      in burn patients. A prospective observational study.
AB  - INTRODUCTION: Matrix metalloproteinases (MMPs) -8 and -9 are released from
      neutrophils in acute inflammation and may contribute to permeability changes in
      burn injury. In retrospective studies on sepsis, levels of MMP-8, MMP-9, and
      tissue inhibitor of metalloproteinase-1 (TIMP-1) differed from those of healthy
      controls, and TIMP-1 showed an association with outcome. Our objective was to
      investigate the relationship between these proteins and disease severity and
      outcome in burn patients. METHODS: In this prospective, observational, two-center
      study, we collected plasma samples from admission to day 21 post-burn, and burn
      blister fluid samples on admission. We compared MMP-8, -9, and TIMP-1 levels
      between TBSA<20% (N = 19) and TBSA>20% (N = 30) injured patients and healthy
      controls, and between 90-day survivors and non-survivors. MMP-8, -9, and TIMP-1
      levels at 24-48 hours from injury, their maximal levels, and their time-adjusted
      means were compared between groups. Correlations with clinical parameters and the
      extent of burn were analyzed. MMP-8, -9, and TIMP-1 levels in burn blister fluids
      were also studied. RESULTS: Plasma MMP-8 and -9 were higher in patients than in
      healthy controls (P<0.001 and P = 0.016), but only MMP-8 differed between the
      TBSA<20% and TBSA>20% groups. MMP-8 and -9 were not associated with clinical
      severity or outcome measures. TIMP-1 differed significantly between patients and
      controls (P<0.001) and between TBSA<20% and TBSA>20% groups (P<0.002). TIMP-1 was
      associated with 90-day mortality and correlated with the extent of injury and
      clinical measures of disease severity. TIMP-1 may serve as a new biomarker in
      outcome prognostication of burn patients.

PMID- 25945789
TI  - Reappraising abstract paintings after exposure to background information.
AB  - Can knowledge help viewers when they appreciate an artwork? Experts' judgments of
      the aesthetic value of a painting often differ from the estimates of naive
      viewers, and this phenomenon is especially pronounced in the aesthetic judgment
      of abstract paintings. We compared the changes in aesthetic judgments of naive
      viewers while they were progressively exposed to five pieces of background
      information. The participants were asked to report their aesthetic judgments of a
      given painting after each piece of information was presented. We found that
      commentaries by the artist and a critic significantly increased the subjective
      aesthetic ratings. Does knowledge enable experts to attend to the visual features
      in a painting and to link it to the evaluative conventions, thus potentially
      causing different aesthetic judgments? To investigate whether a specific pattern
      of attention is essential for the knowledge-based appreciation, we tracked the
      eye movements of subjects while viewing a painting with a commentary by the
      artist and with a commentary by a critic. We observed that critics' commentaries
      directed the viewers' attention to the visual components that were highly
      relevant to the presented commentary. However, attention to specific features of
      a painting was not necessary for increasing the subjective aesthetic judgment
      when the artists' commentary was presented. Our results suggest that at least two
      different cognitive mechanisms may be involved in knowledge- guided aesthetic
      judgments while viewers reappraise a painting. 

PMID- 25945790
TI  - Agent-based mapping of credit risk for sustainable microfinance.
AB  - By drawing analogies with independent research areas, we propose an unorthodox
      framework for mapping microfinance credit risk--a major obstacle to the
      sustainability of lenders outreaching to the poor. Specifically, using the
      elements of network theory, we constructed an agent-based model that obeys the
      stylized rules of microfinance industry. We found that in a deteriorating
      economic environment confounded with adverse selection, a form of latent moral
      hazard may cause a regime shift from a high to a low loan payment probability. An
      after-the-fact recovery, when possible, required the economic environment to
      improve beyond that which led to the shift in the first place. These findings
      suggest a small set of measurable quantities for mapping microfinance credit risk
      and, consequently, for balancing the requirements to reasonably price loans and
      to operate on a fully self-financed basis. We illustrate how the proposed mapping
      works using a 10-year monthly data set from one of the best-known microfinance
      representatives, Grameen Bank in Bangladesh. Finally, we discuss an entirely new
      perspective for managing microfinance credit risk based on enticing spontaneous
      cooperation by building social capital.

PMID- 25945791
TI  - Correction: Evaluation of Hs-CRP Levels and Interleukin 18 (-137G/C) Promoter
      Polymorphism in Risk Prediction of Coronary Artery Disease in First Degree
      Relatives.

PMID- 25945792
TI  - HLA Class II Antigens and Their Interactive Effect on Perinatal Mother-To-Child
      HIV-1 Transmission.
AB  - HLA class II antigens are central in initiating antigen-specific CD4+ T cell
      responses to HIV-1. Specific alleles have been associated with differential
      responses to HIV-1 infection and disease among adults. This study aims to
      determine the influence of HLA class II genes and their interactive effect on
      mother-child perinatal transmission in a drug naive, Mother-Child HIV
      transmission cohort established in Kenya, Africa in 1986. Our study showed that
      DRB concordance between mother and child increased risk of perinatal HIV
      transmission by three fold (P = 0.00035/Pc = 0.0014, OR: 3.09, 95%CI, 1.64-5.83).
      Whereas, DPA1, DPB1 and DQB1 concordance between mother and child had no
      significant influence on perinatal HIV transmission. In addition, stratified
      analysis showed that DRB1*15:03+ phenotype (mother or child) significantly
      increases the risk of perinatal HIV-1 transmission. Without DRB1*15:03, DRB1
      discordance between mother and child provided 5 fold protection (P = 0.00008, OR:
      0.186, 95%CI: 0.081-0.427). However, the protective effect of DRB discordance was
      diminished if either the mother or the child was DRB1*15:03+ phenotype (P = 0.49
      0.98, OR: 0.7-0.99, 95%CI: 0.246-2.956). DRB3+ children were less likely to be
      infected perinatally (P = 0.0006, Pc = 0.014; OR:0.343, 95%CI:0.183-0.642).
      However, there is a 4 fold increase in risk of being infected at birth if DRB3+
      children were born to DRB1*15:03+ mother compared to those with DRB1*15:03-
      mother. Our study showed that DRB concordance/discordance, DRB1*15:03, children's
      DRB3 phenotype and their interactions play an important role in perinatal HIV
      transmission. Identification of genetic factors associated with protection or
      increased risk in perinatal transmission will help develop alternative prevention
      and treatment methods in the event of increases in drug resistance of ARV. 

PMID- 25945793
TI  - A new protocol for evaluating the efficacy of some dispensing systems of a
      packaging in the microbial protection of water-based preservative-free cosmetic
      products.
AB  - OBJECTIVE: A new protocol is described for assessing the efficacy of the
      dispenser of some packaging systems (PSs) of preservative-free cosmetic products
      in protecting both their contained formula and their delivered doses. METHODS:
      Practically, aiming at mimicking contacts with a non-sterile skin or fingers, the
      dispensing system is put into contact with a pre-contaminated fabric by a
      standardized colonization of P. aeruginosa. RESULTS: When applied to three
      different types of packaging, results show clear differences in both criteria
      between these conditioning articles, that is variable efficacies in protecting
      the contained product and the delivered doses, knowing that the first aspect is
      of paramount importance. CONCLUSION: The proposed protocol is proved being able
      to discriminate between different PSs and provides information on strong and weak
      features of certain types dispensing technologies prone to efficiently decrease
      either the dose contamination or to prevent contamination in reaching the
      contained product. Therefore, the proposed protocol can contribute to an
      objective selection of a PS for protecting a cosmetic care product with a low
      content of preservative or preservative free.

PMID- 25945794
TI  - Healthcare-associated infections in children: knowledge, attitudes and practice
      of paediatric healthcare providers at Tygerberg Hospital, Cape Town.
AB  - BACKGROUND: Healthcare (HC) providers' knowledge, attitudes and practices with
      regard to infection control (IC) may positively or adversely affect rates of
      institutional healthcare-associated infection (HAI). OBJECTIVES: To determine
      paediatric HC providers' knowledge, attitudes and practices regarding HAI and
      guide IC interventions in a resource-limited setting. METHODS: Paediatric HC
      providers at Tygerberg Children's Hospital, Cape Town, South Africa completed an
      anonymous, self-administered, 37-item questionnaire. RESULTS: Questionnaires
      (201, 66.6% participation rate) were completed by medical (90, 44.7%), allied
      health (16, 8%) and nursing providers (95, 47.3%). Median age was 34 years (IQR
      27-43), and 84% were female. Knowledge scores were low [57% correct, mean (SD)
      7.7 (1.7)/14 questions] but higher in the medical/allied category (P <= 0.001)
      and those qualified for >= 10 years (P = 0.008). Providers lacked knowledge of
      the main routes of infection transmission and misunderstood hand hygiene and
      terminal cleaning recommendations. Nurses scored higher for attitude questions
      [63% desired responses, mean 5 (1.2)/8 questions] (P = 0.02). Only 38% reported
      adequate undergraduate teaching on HAI and most (93%) wanted more in-service IC
      training. Providers agreed with punitive measures for colleagues ignoring IC
      recommendations (89%). Nurses scored higher for practice questions [53% desired
      responses, mean 3.2 (1.2)/6 questions] (P <= 0.001). Self-reported adherence to
      IC recommendations was high, 88% for hand hygiene and 74% for use of personal
      protective equipment. However, there was poor uptake of annual influenza
      vaccination (25%) and N95 respirator fit-testing (28%), and many felt obliged to
      report for work when sick (67%). DISCUSSION: Expanded in-service and
      undergraduate training in IC should emphasize methods of hand hygiene and routes
      of infection transmission. Paediatric providers support mandatory reporting of
      HAI events and stricter enforcement of IC recommendations.

PMID- 25945795
TI  - Mutations in RECQL Gene Are Associated with Predisposition to Breast Cancer.
AB  - The genetic cause for approximately 80% of familial breast cancer patients is
      unknown. Here, by sequencing the entire exomes of nine early-onset familial
      breast cancer patients without BRCA1/2 mutations (diagnosed with breast cancer at
      or before the age of 35) we found that two index cases carried a potentially
      deleterious mutation in the RECQL gene (RecQ helicase-like; chr12p12). Recent
      studies suggested that RECQL is involved in DNA double-strand break repair and it
      plays an important role in the maintenance of genomic stability. Therefore, we
      further screened the RECQL gene in an additional 439 unrelated familial breast
      cancer patients. In total, we found three nonsense mutations leading to a
      truncated protein of RECQL (p.L128X, p.W172X, and p.Q266X), one mutation
      affecting mRNA splicing (c.395-2A>G), and five missense mutations disrupting the
      helicase activity of RECQL (p.A195S, p.R215Q, p.R455C, p.M458K, and p.T562I), as
      evaluated through an in vitro helicase assay. Taken together, 9 out of 448 BRCA
      negative familial breast cancer patients carried a pathogenic mutation of the
      RECQL gene compared with one of the 1,588 controls (P = 9.14*10-6). Our findings
      suggest that RECQL is a potential breast cancer susceptibility gene and that
      mutations in this gene contribute to familial breast cancer development. 

PMID- 25945796
TI  - Association between Variants in Atopy-Related Immunologic Candidate Genes and
      Pancreatic Cancer Risk.
AB  - BACKGROUND: Many epidemiology studies report that atopic conditions such as
      allergies are associated with reduced pancreas cancer risk. The reason for this
      relationship is not yet understood. This is the first study to comprehensively
      evaluate the association between variants in atopy-related candidate genes and
      pancreatic cancer risk. METHODS: A population-based case-control study of
      pancreas cancer cases diagnosed during 2011-2012 (via Ontario Cancer Registry),
      and controls recruited using random digit dialing utilized DNA from 179 cases and
      566 controls. Following an exhaustive literature review, SNPs in 180 candidate
      genes were pre-screened using dbGaP pancreas cancer GWAS data; 147 SNPs in 56
      allergy-related immunologic genes were retained and genotyped. Logistic
      regression was used to estimate age-adjusted odd ratio (AOR) for each variant and
      false discovery rate was used to adjust Wald p-values for multiple testing.
      Subsequently, a risk allele score was derived based on statistically significant
      variants. RESULTS: 18 SNPs in 14 candidate genes (CSF2, DENND1B, DPP10, FLG,
      IL13, IL13RA2, LRP1B, NOD1, NPSR1, ORMDL3, RORA, STAT4, TLR6, TRA) were
      significantly associated with pancreas cancer risk. After adjustment for multiple
      comparisons, two LRP1B SNPs remained statistically significant; for example,
      LRP1B rs1449477 (AA vs. CC: AOR=0.37, 95% CI: 0.22-0.62; p (adjusted)=0.04).
      Furthermore, the risk allele score was associated with a significant reduction in
      pancreas cancer risk (p=0.0007). CONCLUSIONS: Preliminary findings suggest
      certain atopy-related variants may be associated with pancreas cancer risk.
      Further studies are needed to replicate this, and to elucidate the biology behind
      the growing body of epidemiologic evidence suggesting allergies may reduce
      pancreatic cancer risk.

PMID- 25945797
TI  - Conformational transition in signal transduction: metastable states and
      transition pathways in the activation of a signaling protein.
AB  - Signal transduction is of vital importance to the growth and adaptation of living
      organisms. The key to understand mechanisms of biological signal transduction is
      elucidation of the conformational dynamics of its signaling proteins, as the
      activation of a signaling protein is fundamentally a process of conformational
      transition from an inactive to an active state. A predominant form of signal
      transduction for bacterial sensing of environmental changes in the wild or inside
      their hosts is a variety of two-component systems, in which the conformational
      transition of a response regulator (RR) from an inactive to an active state
      initiates responses to the environmental changes. Here, RR activation has been
      investigated using RR468 as a model system by extensive unbiased all-atom
      molecular dynamics (MD) simulations in explicit solvent, starting from snapshots
      along a targeted MD trajectory that covers the conformational transition. Markov
      state modeling, transition path theory, and geometric analyses of the wealth of
      the MD data have provided a comprehensive description of the RR activation. It
      involves a network of metastable states, with one metastable state essentially
      the same as the inactive state and another very similar to the active state that
      are connected via a small set of intermediates. Five major pathways account for
      >75% of the fluxes of the conformational transition from the inactive to the
      active-like state. The thermodynamic stability of the states and the activation
      barriers between states are found, to identify rate-limiting steps. The conformal
      transition is initiated predominantly by movements of the beta3alpha3 loop,
      followed by movements of the beta4alpha4-loop and neighboring alpha4 helix
      region, and capped by additional movements of the beta3alpha3 loop. A number of
      transient hydrophobic and hydrogen bond interactions are revealed, and they may
      be important for the conformational transition. 

PMID- 25945798
TI  - Assembly of a comprehensive regulatory network for the mammalian circadian clock:
      a bioinformatics approach.
AB  - By regulating the timing of cellular processes, the circadian clock provides a
      way to adapt physiology and behaviour to the geophysical time. In mammals, a
      light-entrainable master clock located in the suprachiasmatic nucleus (SCN)
      controls peripheral clocks that are present in virtually every body cell.
      Defective circadian timing is associated with several pathologies such as cancer
      and metabolic and sleep disorders. To better understand the circadian regulation
      of cellular processes, we developed a bioinformatics pipeline encompassing the
      analysis of high-throughput data sets and the exploitation of published knowledge
      by text-mining. We identified 118 novel potential clock-regulated genes and
      integrated them into an existing high-quality circadian network, generating the
      to-date most comprehensive network of circadian regulated genes (NCRG). To
      validate particular elements in our network, we assessed publicly available ChIP
      seq data for BMAL1, REV-ERBalpha/beta and RORalpha/gamma proteins and found
      strong evidence for circadian regulation of Elavl1, Nme1, Dhx6, Med1 and Rbbp7
      all of which are involved in the regulation of tumourigenesis. Furthermore, we
      identified Ncl and Ddx6, as targets of RORgamma and REV-ERBalpha, beta,
      respectively. Most interestingly, these genes were also reported to be involved
      in miRNA regulation; in particular, NCL regulates several miRNAs, all involved in
      cancer aggressiveness. Thus, NCL represents a novel potential link via which the
      circadian clock, and specifically RORgamma, regulates the expression of miRNAs,
      with particular consequences in breast cancer progression. Our findings bring us
      one step forward towards a mechanistic understanding of mammalian circadian
      regulation, and provide further evidence of the influence of circadian
      deregulation in cancer. 

PMID- 25945799
TI  - Cellular Responses Modulated by FGF-2 Adsorbed on Albumin/Heparin Layer-by-Layer
      Assemblies.
AB  - In a typical cell culture system, growth factors immobilized on the cell culture
      surfaces can serve as a reservoir of bio-signaling molecules, without the need to
      supplement them additionally into the culture medium. In this paper, we report on
      the fabrication of albumin/heparin (Alb/Hep) assemblies for controlled binding of
      basic fibroblast growth factor (FGF-2). The surfaces were constructed by layer-by
      layer adsorption of polyelectrolytes albumin and heparin and were subsequently
      stabilized by covalent crosslinking with glutaraldehyde. An analysis of the
      surface morphology by atomic force microscopy showed that two Alb/Hep bilayers
      are required to cover the surface of substrate. The formation of the Alb/Hep
      assemblies was monitored by the surface plasmon resonance (SPR), the infrared
      multiinternal reflection spectroscopy (FTIR MIRS) and UV/VIS spectroscopy. The
      adsorption of FGF-2 on the cross-linked Alb/Hep was followed by SPR. The results
      revealed that FGF-2 binds to the Alb/Hep assembly in a dose and time-dependent
      manner up to the surface concentration of 120 ng/cm(2). The bioactivity of the
      adsorbed FGF-2 was assessed in experiments in vitro, using calf pulmonary
      arterial endothelial cells (CPAE). CPAE cells could attach and proliferate on
      Alb/Hep surfaces. The adsorbed FGF-2 was bioactive and stimulated both the
      proliferation and the differentiation of CPAE cells. The improvement was more
      pronounced at a lower FGF-2 surface concentration (30 ng/cm(2)) than on surfaces
      with a higher concentration of FGF-2 (120 ng/cm(2)).

PMID- 25945800
TI  - The fragrant power of collective fear.
AB  - Fear is a well-characterized biological response to threatening or stressful
      situations in humans and other social animals. Importantly, fearful stimuli in
      the natural environment are likely to be encountered concurrently by a group of
      animals. The modulation of fear acquisition and fear memory by a group as opposed
      to an individual experience, however, remains largely unknown. Here, we
      demonstrate a robust reduction in fear memory to an aversive event undertaken in
      a group despite similar fear learning between individually- and group-conditioned
      rats. This reduction persists outside the group confines, appears to be a direct
      outcome of group cognizance and is counteracted by loss of olfactory signaling
      among the group members. These results show that a group experience of fear can
      be protective and suggest that distinct neural pathways from those classically
      studied in individuals modulate collective fear memories. 

PMID- 25945801
TI  - Glutathione S-Transferase (GST) Gene Diversity in the Crustacean Calanus
      finmarchicus--Contributors to Cellular Detoxification.
AB  - Detoxification is a fundamental cellular stress defense mechanism, which allows
      an organism to survive or even thrive in the presence of environmental toxins
      and/or pollutants. The glutathione S-transferase (GST) superfamily is a set of
      enzymes involved in the detoxification process. This highly diverse protein
      superfamily is characterized by multiple gene duplications, with over 40 GST
      genes reported in some insects. However, less is known about the GST superfamily
      in marine organisms, including crustaceans. The availability of two de novo
      transcriptomes for the copepod, Calanus finmarchicus, provided an opportunity for
      an in depth study of the GST superfamily in a marine crustacean. The
      transcriptomes were searched for putative GST-encoding transcripts using known
      GST proteins from three arthropods as queries. The identified transcripts were
      then translated into proteins, analyzed for structural domains, and annotated
      using reciprocal BLAST analysis. Mining the two transcriptomes yielded a total of
      41 predicted GST proteins belonging to the cytosolic, mitochondrial or microsomal
      classes. Phylogenetic analysis of the cytosolic GSTs validated their annotation
      into six different subclasses. The predicted proteins are likely to represent the
      products of distinct genes, suggesting that the diversity of GSTs in C.
      finmarchicus exceeds or rivals that described for insects. Analysis of relative
      gene expression in different developmental stages indicated low levels of GST
      expression in embryos, and relatively high expression in late copepodites and
      adult females for several cytosolic GSTs. A diverse diet and complex life history
      are factors that might be driving the multiplicity of GSTs in C. finmarchicus, as
      this copepod is commonly exposed to a variety of natural toxins. Hence, diversity
      in detoxification pathway proteins may well be key to their survival. 

PMID- 25945803
TI  - Use and outcome of radial versus femoral approach for primary PCI in patients
      with acute ST elevation myocardial infarction without cardiogenic shock: results
      from the ALKK PCI registry.
AB  - OBJECTIVES: This study sought to compare the use and outcome of radial versus
      femoral access in patients treated with primary percutaneous coronary
      intervention (PCI) for acute ST elevation myocardial infarction (STEMI) in
      clinical practice. BACKGROUND: The radial approach for PCI in patients with STEMI
      has been suggested to have a lower rate of complications and bleeding and to
      improve prognosis compared with the femoral approach. However, there still is a
      large regional and national variation in its use. METHODS: Between 2008 and 2012
      a total of 17,865 patients with STEMI without cardiogenic shock undergoing
      primary PCI were prospectively enrolled in the observational German PCI registry
      of the Arbeitsgemeinschaft leitende kardiologische Krankenhausarzte (ALKK).
      Transfemoral (TF) access was used in 15,270 (85.5%), transradial (TR) access in
      2,530 (14.2%), and other access in 65 (0.3%) patients. In this analysis, 10,264
      patients from 20 centers that had performed at least 5 TR-PCI for STEMI were
      included. This study compared TR-PCI (n = 2,454 23.9%) with TF-PCI (n = 7,810,
      76.1%). RESULTS: Procedural success was high in both cohorts. Hospital mortality
      (1.8 vs. 5.1%, P < 0.001) and vascular access complications (0.3 vs. 1.8%, P <
      0.001%) were lower in the TR group. In the multivariate analysis radial access
      was associated with an improved in-hospital survival rate (OR 0.47, 95% CI 0.35
      0.65). CONCLUSIONS: The radial approach for PCI can be performed with excellent
      procedural success in selected STEMI patients and is associated with a lower rate
      of vascular access complications and hospital mortality.

PMID- 25945802
TI  - Brain-Derived Neurotrophic Factor Expression in Asthma. Association with Severity
      and Type 2 Inflammatory Processes.
AB  - Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family,
      exists in several isoforms, which differentially impacts neuronal and immune cell
      survival and differentiation. The role of BDNF and its isoforms in asthma remains
      unclear. The objectives of this study were to compare the BDNF protein isoforms
      and specific splice variant expression in sputum and bronchoscopic samples from
      healthy control subjects and participants with asthma, and to relate these
      changes to findings in IL-13-stimulated human airway epithelial cells. Sputum and
      bronchoscopic samples from healthy control subjects and participants with asthma
      were evaluated for BDNF protein (ELISA and Western blot) and BDNF mRNA (gel and
      quantitative real-time PCR) in relation to asthma severity and type 2
      inflammatory processes. BDNF mRNA was measured in cultured primary human airway
      epithelial cells after IL-13 stimulation. Total BDNF protein differed among the
      groups, and its mature isoform was significantly higher in sputum from subjects
      with severe asthma compared with healthy control subjects (overall P = 0.008, P =
      0.027, respectively). Total BDNF was higher in those with elevated fractional
      exhaled nitric oxide and sputum eosinophilia. In vitro, IL-13 increased BDNF exon
      VIb splice variant and the ratio to BDNF common exon IX mRNA (P < 0.001, P =
      0.003, respectively). Epithelial brushing exon VIb mRNA and total BDNF protein
      differed among the groups and were higher in subjects with severe asthma than in
      healthy control subjects (overall P = 0.01, P = 0.02, respectively). The mature
      BDNF isoform and the exon VIb splice variant are increased in human asthmatic
      airways. The in vitro increase in response to IL-13 suggests that type 2
      cytokines regulate BDNF levels and activity in asthma. 

PMID- 25945804
TI  - Long-term outcome of critically ill adult patients with acute epiglottitis.
AB  - BACKGROUND: Acute epiglottitis is a potentially life threatening disease, with a
      growing incidence in the adult population. Its long-term outcome after Intensive
      Care Unit (ICU) hospitalization has rarely been studied. METHODOLOGY AND
      PRINCIPAL FINDINGS: Thirty-four adult patients admitted for acute epiglottitis
      were included in this retrospective multicentric study. The mean age was 44 +/-
      12 years (sex ratio: 5.8). Sixteen patients (47%) had a history of smoking while
      8 (24%) had no previous medical history. The average time of disease progression
      before ICU was 2.6 +/- 3.6 days. The main reasons for hospitalization were
      continuous monitoring (17 cases, 50%) and acute respiratory distress (10 cases,
      29%). Microbiological documentation could be made in 9 cases (26%), with
      Streptococcus spp. present in 7 cases (21%). Organ failure at ICU admission
      occurred in 8 cases (24%). Thirteen patients (38%) required respiratory
      assistance during ICU stay; 9 (26%) required surgery. Two patients (6%) died
      following hypoxemic cardiac arrest. Five patients (15%) had sequelae at 1 year.
      Patients requiring respiratory assistance had a longer duration of symptoms and
      more frequent anti inflammatory use before ICU admission and sequelae at 1 year
      (p < 0.05 versus non-ventilated patients). After logistic regression analysis,
      only exposure to anti-inflammatory drugs before admission was independently
      associated with airway intervention (OR, 4.96; 95% CI, 1.06-23.16). CONCLUSIONS
      AND SIGNIFICANCE: The profile of the cases consisted of young smoking men with
      little comorbidity. Streptococcus spp. infection represented the main etiology.
      Outcome was favorable if early respiratory tract protection could be performed in
      good conditions. Morbidity and sequelae were greater in patients requiring airway
      intervention.

PMID- 25945805
TI  - Transcervical ultrasonography in the diagnosis of pediatric peritonsillar
      abscess.
AB  - OBJECTIVES/HYPOTHESIS: Pediatric peritonsillar abscess (PTA) is a common
      infection, particularly in the adolescent population. Physical examination alone
      is not always sufficient to diagnose this pathology, and thus, computed
      tomography is often utilized as a diagnostic adjunct. With growing concern over
      radiation exposure in the pediatric population, we conducted a prospective study
      to investigate the use of ultrasonography in the detection of pediatric PTA.
      STUDY DESIGN: Prospective single arm cohort study. METHODS: Pediatric patients
      examined in consultation for concern for PTA were prospectively enrolled in the
      study. Patients were managed based on clinical symptoms and presentation.
      Transcervical ultrasonography of the peritonsillar region was performed on all
      patients. Clinical outcomes were reviewed retrospectively and compared to
      ultrasound findings. RESULTS: Forty-three patients (age range, 2-20 years) were
      enrolled in the study. The sensitivity and specificity of transcervical
      ultrasound when compared to clinical outcomes were 100% and 76.5%, respectively.
      The positive and negative predictive values were 52.9% and 100%, respectively.
      Fisher exact test showed a statistically significant association (P < .01)
      between negative ultrasonography and successful medical management, and
      multivariate regression analysis showed a strong correlation between ultrasound
      findings and presence/absence of purulence during surgical intervention (P =
      .01). CONCLUSIONS: Transcervical ultrasonography is a useful tool in diagnosing
      pediatric PTA. This imaging modality not only avoids undue radiation exposure,
      but it also proves to be an excellent tool at identifying patients who will not
      need surgical intervention. To our knowledge, this is the first study to explore
      this technique for the diagnosis of pediatric PTA. LEVEL OF EVIDENCE: 2b.

PMID- 25945807
TI  - Multi-centre validation of the prognostic value of the haematopoietic cell
      transplantation- specific comorbidity index among recipient of allogeneic
      haematopoietic cell transplantation.
AB  - The haematopoietic cell transplantation-specific comorbidity index (HCT-CI) was
      developed in a single centre as a weighted scoring system to predict risks of non
      relapse mortality (NRM) following allogeneic haematopoietic cell transplantation.
      Information on the performance of the HCT-CI in multi-centre studies is lacking
      in the literature. To that end, a collaborative multicentre retrospective study
      was initiated. Comorbidity data from 2523 consecutive recipients of human
      leucocyte antigen-matched grafts from five different US institutions were
      analysed. Among all patients, HCT-CI scores of 0 vs. 1-2 vs. >=3 were associated
      with 2-year NRM rates of 14%, 23% and 39% (P < 0.0001), respectively, and 2-year
      overall survival (OS) rates of 74%, 61% and 39%, respectively (P < 0.0001). Using
      regression models, increasing HCT-CI scores were independently associated with
      increases in hazard ratios for NRM and worse survival within individual
      institutions. The HCT-CI retained independent capacity for association with
      outcomes within different age as well as conditioning intensity groups. C
      statistic estimates for the prognostic power of the HCT-CI for NRM and OS were
      0.66 and 0.64, respectively. The estimates within each institution were overall
      similar. The HCT-CI is a valid tool for capturing comorbidities and predicting
      mortality after haematopoietic cell transplantation across different
      institutions. 

PMID- 25945808
TI  - First-In-Human Study Demonstrating Tumor-Angiogenesis by PET/CT Imaging with
      (68)Ga-NODAGA-THERANOST, a High-Affinity Peptidomimetic for alphavbeta3 Integrin
      Receptor Targeting.
AB  - (68)Ga-NODAGA-THERANOSTTM is an alphavbeta3 integrin antagonist and the first
      radiolabeled peptidomimetic to reach clinical development for targeting integrin
      receptors. In this first-in-human study, the feasibility of integrin receptor
      peptidomimetic positron emission tomography/computed tomography (PET/CT) imaging
      was confirmed in patients with non-small-cell lung cancer and breast cancer.
      METHODS: Patients underwent PET/CT imaging with (68)Ga NODAGA-THERANOST. PET
      images were analyzed qualitatively and quantitatively and compared to 2-deoxy-2
      ((18)F) fluoro-d-glucose ((18)F-FDG) findings. Images were obtained 60 minutes
      postinjection of 300-500 MBq of (68)Ga-NODAGA-THERANOST. RESULTS: (68)Ga-NODAGA
      THERANOST revealed high tumor-to-background ratios (SUVmax=4.8) and uptake at
      neoangiogenesis sites. Reconstructed fused images distinguished cancers with high
      malignancy potential and enabled enhanced bone metastasis detection. (18)F-FDG
      positive lung and lymph node metastases did not show uptake, indicating the
      absence of neovascularization. CONCLUSIONS: (68)Ga-NODAGA-THERANOST was found to
      be safe and effective, exhibiting in this study rapid blood clearance, stability,
      rapid renal excretion, favorable biodistribution and PK/PD, low irradiation
      burden (MUSv/MBq/MUg), and convenient radiolabeling. This radioligand might
      enable theranostics, that is, a combination of diagnostics followed by the
      appropriate therapeutics, namely antiangiogenic therapy, image-guided presurgical
      assessment, treatment response evaluation, prediction of pathologic response,
      neoadjuvant-peptidomimetic-radiochemotherapy, and personalized medicine
      strategies. Further clinical trials evaluating (68)Ga-NODAGA-THERANOST are
      warranted.

PMID- 25945809
TI  - Structural insights into thyroid hormone transport mechanisms of the L-type amino
      acid transporter 2.
AB  - Thyroid hormones (THs) are transported across cell membranes by different
      transmembrane transporter proteins. In previous studies, we showed marked 3,3'
      diiodothyronine (3,3'-T2) but moderate T3 uptake by the L-type amino acid
      transporter 2 (Lat2). We have now studied the structure-function relationships of
      this transporter and TH-like molecules. Our Lat2 homology model is based on 2
      crystal structures of the homologous 12-transmembrane helix transporters
      arginine/agmatine antiporter and amino acid/polyamine/organocation transporter.
      Model-driven mutagenesis of residues lining an extracellular recognition site and
      a TH-traversing channel identified 9 sensitive residues. Using Xenopus laevis
      oocytes as expression system, we found that side chain shortening (N51S, N133S,
      N248S, and Y130A) expanded the channel and increased 3,3'-T2 transport. Side
      chain enlargements (T140F, Y130R, and I137M) decreased 3,3'-T2 uptake, indicating
      channel obstructions. The opposite results with mutations maintaining (F242W) or
      impairing (F242V) uptake suggest that F242 may have a gating function.
      Competitive inhibition studies of 14 TH-like compounds revealed that recognition
      by Lat2 requires amino and carboxylic acid groups. The size of the adjacent
      hydrophobic group is restricted. Bulky substituents in positions 3 and 5 of the
      tyrosine ring are allowed. The phenolic ring may be enlarged, provided that the
      whole molecule is flexible enough to fit into the distinctly shaped TH-traversing
      channel of Lat2. Taken together, the next Lat2 features were identified 1) TH
      recognition site; 2) TH-traversing channel in the center of Lat2; and 3) switch
      site that potentially facilitates intracellular substrate release. Together with
      identified substrate features, these data help to elucidate the molecular
      mechanisms and role of Lat2 in T2 transport. 

PMID- 25945810
TI  - Efficient low-temperature transparent electrocatalytic layers based on graphene
      oxide nanosheets for dye-sensitized solar cells.
AB  - Electrocatalytic materials with a porous structure have been fabricated on glass
      substrates, via high-temperature fabrication, for application as alternatives to
      platinum in dye-sensitized solar cells (DSCs). Efficient, nonporous, nanometer
      thick electrocatalytic layers based on graphene oxide (GO) nanosheets were
      prepared on plastic substrates using electrochemical control at low temperatures
      of <=100  degrees C. Single-layer, oxygen-rich GO nanosheets prepared on indium
      tin oxide (ITO) substrates were electrochemically deoxygenated in acidic medium
      within a narrow scan range in order to obtain marginally reduced GO at minimum
      expense of the oxygen groups. The resulting electrochemically reduced GO (E-RGO)
      had a high density of residual alcohol groups with high electrocatalytic activity
      toward the positively charged cobalt-complex redox mediators used in DSCs. The
      ultrathin, alcohol-rich E-RGO layer on ITO-coated poly(ethylene terephthalate)
      was successfully applied as a lightweight, low-temperature counter electrode with
      an extremely high optical transmittance of ~97.7% at 550 nm. A cobalt(II/III)
      mediated DSC employing the highly transparent, alcohol-rich E-RGO electrode
      exhibited a photovoltaic power conversion efficiency of 5.07%. This is superior
      to that obtained with conventionally reduced GO using hydrazine (3.94%) and even
      similar to that obtained with platinum (5.10%). This is the first report of a
      highly transparent planar electrocatalytic layer based on carbonaceous materials
      fabricated on ITO plastics for application in DSCs. 

PMID- 25945811
TI  - Endothelial cell-anchored tissue factor pathway inhibitor regulates tumor
      metastasis to the lung in mice.
AB  - Tissue factor pathway inhibitor (TFPI) is a physiological inhibitor of the tissue
      factor (TF)-initiated coagulation pathway. Both circulating and tumor cell
      associated TFPI significantly reduce tumor cell-induced coagulation activation
      and lung metastasis. However, the significance of endothelial cell-anchored TFPI
      in cancer biology remains largely unexplored. We generated mice with full-length
      disruption of TFPI (including TFPIalpha and TFPIbeta isoforms) in endothelial
      cells, using a Cre-LoxP system and gene inactivation (GI) strategy. Experimental
      pulmonary tumor metastasis models were used with TFPI-deficient mice to evaluate
      the role of endothelial cell-anchored TFPI in cancer progression. Finally, lung
      microvascular permeability and microenvironment were investigated. TFPI-deficient
      mice were viable and fertile, and showed decreased plasma TFPI levels and lung
      TFPI levels as compared with their control littermates. TFPI deficiency in
      endothelial cells promoted pulmonary tumor metastasis with an increased vascular
      permeability and altered lung microenvironment. Our observations suggest that
      endothelial cell-anchored TFPI controls lung tumor metastasis, and does so
      largely through the inhibition of local TF-induced thrombin generation and the
      regulation of the lung microenvironment in mice.

PMID- 25945812
TI  - Succinylated Apoptolidins from Amycolatopsis sp. ICBB 8242.
AB  - Two new apoptolidins, 2'-O-succinyl-apoptolidin A (11) and 3'-O-succinyl
      apoptolidin A (12), were isolated from the culture broth of an Indonesian
      Amycolatopsis sp. ICBB 8242. These compounds inhibit the proliferation and
      viability of human H292 and HeLa cells. However, in contrast to apoptolidin A
      (1), they do not inhibit cellular respiration in H292 cells. It is proposed that
      apoptolidins are produced and secreted in their succinylated forms and 1 is the
      hydrolysis product of 11 and 12. 

PMID- 25945813
TI  - Relationship between maternal and newborn endothelial function and oxidative
      stress.
AB  - OBJECTIVE: To evaluate the Relationship between maternal and newborn endothelial
      function and oxidative stress. METHODS: Forty-three pregnant women and their
      offspring were evaluated. As markers of endothelial function, the flow-mediated
      dilation (FMD) was measured in pregnant women in the second and third trimesters,
      and nitric oxide (NO) was quantified in the endothelial cells of the umbilical
      cord vein. Malondialdehyde (MDA), as a marker of oxidative stress, was measured
      in the maternal plasma (second and third trimesters) and plasma from umbilical
      cord blood. Gestational age and birth weight were recorded. Correlations between
      variables were estimated, and adjustments were made for specific gestational week
      of measurement, gestational age at birth, and complications during pregnancy
      and/or at delivery. RESULTS: Maternal FMD at second trimester correlated
      positively with newborn MDA, although with marginal significance (P = 0.090). The
      change in maternal FMD was positively correlated with newborn NO (P = 0.039),
      although adjustment for gestational age and specific week of gestation attenuated
      this relationship (P = 0.070). Maternal MDA at second trimester correlated
      positively with newborn MDA independently of gestational age at birth, specific
      week of gestation of the measurement, and having complications during pregnancy
      or at delivery (P = 0.032). After adjustments, the change in maternal MDA
      correlated with newborn MDA but marginally (P = 0.077). CONCLUSION: Study
      findings suggest that under physiological conditions, enhanced endothelial
      function and/or oxidative stress in the mother may impact on normal fetal
      development. Future studies are recommended, employing larger sample sizes, a
      more extensive set of markers of oxidative stress, and comparisons of complicated
      versus normal pregnancies.

PMID- 25945814
TI  - Applying mass spectrometry to study non-covalent biomolecule complexes.
AB  - Non-covalent interactions are essential for the structural organization of
      biomacromolecules and play an important role in molecular recognition processes,
      such as the interactions between proteins, glycans, lipids, DNA, and RNA. Mass
      spectrometry (MS) is a powerful tool for studying of non-covalent interactions,
      due to the low sample consumption, high sensitivity, and label-free nature.
      Nowadays, native-ESI MS is heavily used in studies of non-covalent interactions
      and to understand the architecture of biomolecular complexes. However, MALDI-MS
      is also becoming increasingly useful. It is challenging to detect the intact
      complex without fragmentation when analyzing non-covalent interactions with MALDI
      MS. There are two methodological approaches to do so. In the first approach,
      different experimental and instrumental parameters are fine-tuned in order to
      find conditions under which the complex is stable, such as applying non-acidic
      matrices and collecting first-shot spectra. In the second approach, the
      interacting species are "artificially" stabilized by chemical crosslinking. Both
      approaches are capable of studying non-covalently bound biomolecules even in
      quite challenging systems, such as membrane protein complexes. Herein, we review
      and compare native-ESI and MALDI MS for the study of non-covalent interactions.

PMID- 25945815
TI  - A comparative investigation of bone surface after cutting with mechanical tools
      and Er:YAG laser.
AB  - BACKGROUND AND OBJECTIVES: Despite of the long history of medical application,
      laser ablation of bone tissue became successful only recently. Laser bone cutting
      is proven to have higher accuracy and to increase bone healing compared to
      conventional mechanical bone cutting. But the reason of subsequent better healing
      is not biologically explained yet. In this study we present our experience with
      an integrated miniaturized laser system mounted on a surgical lightweight robotic
      arm. STUDY DESIGN/MATERIALS AND METHODS: An Erbium-doped Yttrium Aluminium Garnet
      (Er:YAG) laser and a piezoelectric (PZE) osteotome were used for comparison. In
      six grown up female Gottingen minipigs, comparative surgical interventions were
      done on the edentulous mandibular ridge. Our laser system was used to create
      different shapes of bone defects on the left side of the mandible. On the
      contralateral side, similar bone defects were created by PZE osteotome. Small
      bone samples were harvested to compare the immediate post-operative cut surface.
      RESULTS: The analysis of the cut surface of the laser osteotomy and conventional
      mechanical osteotomy revealed an essential difference. The scanning electron
      microscopy (SEM) analysis showed biologically open cut surfaces from the laser
      osteotomy. The samples from PZE osteotomy showed a flattened tissue structure
      over the cut surface, resembling the "smear layer" from tooth preparation.
      CONCLUSIONS: We concluded that our new finding with the mechanical osteotomy
      suggests a biological explanation to the expected difference in subsequent bone
      healing. Our hypothesis is that the difference of surface characteristic yields
      to different bleeding pattern and subsequently results in different bone healing.
      The analyses of bone healing will support our hypothesis.

PMID- 25945816
TI  - Evaluating the User Experience of Exercising Reaching Motions With a Robot That
      Predicts Desired Movement Difficulty.
AB  - The notion of an optimal difficulty during practice has been articulated in many
      areas of cognitive psychology: flow theory, the challenge point framework, and
      desirable difficulties. Delivering exercises at a participant's desired
      difficulty has the potential to improve both motor learning and users' engagement
      in therapy. Motivation and engagement are among the contributing factors to the
      success of exercise programs. The authors previously demonstrated that error
      amplification can be used to introduce levels of challenge into a robotic
      reaching task, and that machine-learning algorithms can dynamically adjust
      difficulty to the desired level with 85% accuracy. Building on these findings, we
      present the results of a proof-of-concept study investigating the impacts of
      practicing under desirable difficulty conditions. A control condition with a
      predefined random order for difficulty levels was deemed more suitable for this
      study (compared to constant or continuously increasing difficulty). By practicing
      the task at their desirable difficulties, participants in the experimental group
      perceived their performance at a significantly higher level and reported lower
      required effort to complete the task, in comparison to a control group. Moreover,
      based on self-reports, participants in the experimental group were willing, on
      average, to continue the training session for 4.6 more training blocks (~45 min)
      compared to the control group's average. This study demonstrates the efficiency
      of delivering the exercises at the user's desired difficulty level to improve the
      user's engagement in exercise tasks. Future work will focus on clinical
      feasibility of this approach in increasing stroke survivors' engagement in their
      therapy programs. 

PMID- 25945818
TI  - Malleable and Self-Healing Covalent Polymer Networks through Tunable Dynamic
      Boronic Ester Bonds.
AB  - Despite numerous strategies involving dynamic covalent bond exchange for dynamic
      and self-healing materials, it remains a challenge to be able to tune the
      malleability and self-healing properties of bulk materials through simple small
      molecule perturbations. Here we describe the use of tunable rates of boronic
      ester transesterification to tune the malleability and self-healing efficiencies
      of bulk materials. Specifically, we used two telechelic diboronic ester small
      molecules with variable transesterification kinetics to dynamically cross-link
      1,2-diol-containing polymer backbones. The sample cross-linked with fast
      exchanging diboronic ester showed enhanced malleability and accelerated healing
      compared to the slow-exchanging variant under the same conditions. Our report
      demonstrates the possibility of transferring small molecule kinetics to dynamic
      properties of bulk solid material and may serve as a guide for the rational
      design of tunable dynamic materials. 

PMID- 25945817
TI  - MiR-221 as a pre- and postoperative plasma biomarker for larynx cancer patients.
AB  - OBJECTIVE: In order to identify a plasma microRNA (miRNA) signature of larynx
      cancer (LCa), we examined miRNAs profile of plasma samples obtained from 30 LCa
      patients (preoperative and postoperative serum samples) and 30 healthy controls.
      STUDY DESIGN: Basic science research study. METHODS: MicroRNA profiling of eight
      plasma samples (four from preoperative, four from control individuals) were
      performed using miRNA microarray. Two of the significantly deregulated miRNAs
      were selected for further confirmation in the remaining samples using
      quantitative reverse-transcription polymerase chain reaction (qRT-PCR). RESULTS:
      Microarray profiling and qRT-PCR analysis showed that miR-221 was upregulated in
      LCa plasma samples. Further qRT-PCR analysis demonstrated that miR-221 was at
      normal levels in postoperative plasma samples. CONCLUSIONS: Plasma miR-221 may
      have a potential as a novel diagnostic/prognostic marker and might be considered
      as a therapeutic target in LCa. LEVEL OF EVIDENCE: N/A.

PMID- 25945819
TI  - Context for practice: setting the standard for ostomy nursing.

PMID- 25945820
TI  - Universal Pressure Ulcer Prevention Bundle With WOC Nurse Support.
AB  - PURPOSE: This study examined the effectiveness of a universal pressure ulcer
      prevention bundle (UPUPB) applied to intensive care unit (ICU) patients combined
      with proactive, semiweekly WOC nurse rounds. The UPUBP was compared to a standard
      guideline with referral-based WOC nurse involvement measuring adherence to 5
      evidence-based prevention interventions and incidence of pressure ulcers. DESIGN:
      The study used a quasi-experimental, pre-, and postintervention design in which
      each phase included different subjects. Descriptive methods assisted in exploring
      the content of WOC nurse rounds. SUBJECT AND SETTING: One hundred eighty-one pre-
      and 146 postintervention subjects who met inclusion criteria and were admitted to
      ICU for more than 24 hours participated in the study. The research setting was 3
      ICUs located at North Memorial Medical Center in Minneapolis, Minnesota. METHODS:
      Data collection included admission/discharge skin assessments, chart reviews for
      5 evidence-based interventions and patient characteristics, and WOC nurse
      rounding logs. Study subjects with intact skin on admission identified with an
      initial skin assessment were enrolled in which prephase subjects received
      standard care and postphase subjects received the UPUPB. Skin assessments on ICU
      discharge and chart reviews throughout the stay determined the presence of unit
      acquired pressure ulcers and skin care received. Analysis included description of
      WOC nurse rounds, t-tests for guideline adherence, and multivariate analysis for
      intervention effect on pressure ulcer incidence. Unit assignment, Braden Scale
      score, and ICU length of stay were covariates for a multivariate model based on
      bivariate logistic regression screening. RESULTS: The incidence of unit-acquired
      pressure ulcers decreased from 15.5% to 2.1%. WOC nurses logged 204 rounds over 6
      months, focusing primarily on early detection of pressure sources. Data analysis
      revealed significantly increased adherence to heel elevation (t = -3.905, df =
      325, P < .001) and repositioning (t = -2.441, df = 325, P < .015). Multivariate
      logistic regression modeling showed a significant reduction in unit-acquired
      pressure ulcers (P < .001). The intervention increased the Nagelkerke R-Square
      value by 0.099 (P < .001) more than 0.297 (P < .001) when including only
      covariates, for a final model value of 0.396 (P < .001). CONCLUSION: The UPUPB
      with WOC nurse rounds resulted in a statistically significant and clinically
      relevant reduction in the incidence of pressure ulcers.

PMID- 25945821
TI  - Evaluation of a bovine 100% native collagen for the treatment of chronic wounds:
      a case series.
AB  - PURPOSE: The roles of debridement, infection control, and moisture balance in
      wound healing are familiar to wound care clinicians, but these measures may not
      be sufficient for wound closure in all patients. In these cases, adjuvant
      therapies such as collagen dressings may be needed. Collagen dressings are
      thought to encourage wound healing by laying down a provisional biomaterial
      matrix that captures wound exudates because of its absorbent nature, and thus
      creates an environment necessary for healing. This case series describes our
      experience with a bovine-derived, 100% native, type I collagen in patients with
      chronic and persistent wounds. CASES: This case series included 20 patients with
      21 chronic wounds ranging from 0.6 to 101.4 cm(2) that had been recalcitrant to
      prior conservative treatment and/or the use of submucosal intestinal matrix,
      oxidized regenerated cellulose/collagen matrix, or skin substitute. In addition
      to the bovine-derived 100% native collagen, standard wound care included the use
      of any systemic or topical antimicrobial treatments needed to specifically
      address wound infections. The total duration of treatment with the bovine-derived
      100% native collagen was up to 12 weeks. Complete wound healing was achieved for
      15 of the patients in this series; wound healing times varied from 13 to 68 days.
      Two additional patients achieved wound healing, using a combination of the bovine
      derived 100% native collagen and other therapies, at 114 days and 107 days,
      respectively, after starting the wound healing process with solely the bovine
      derived 100% native collagen treatment. One patient did not respond to treatment.
      The collagen treatment was well tolerated by the patients, with 3 incidences of
      dermatitis that resolved after treatment with corticosteroids. CONCLUSION:
      Following a change in their chronic wound care regimen to include a bovine
      derived, 100% native, type I collagen, we achieved an 83.3% (15 out of 18
      patients) wound closure rate. Two patients were excluded from the data set
      analysis because they received additional intervention outside the parameters
      described in this multiple-case series.

PMID- 25945822
TI  - Analysis of qualitative interviews about the impact of information technology on
      pressure ulcer prevention programs: implications for the wound, ostomy and
      continence nurse.
AB  - PURPOSE: The purpose of this study was to compare pressure ulcer prevention
      programs in 2 long-term care (LTC) facilities with diverse Information Technology
      Sophistication (ITS), one with high sophistication and one with low
      sophistication, and to identify implications for the WOC nurse. DESIGN: Secondary
      analysis of narrative data obtained from a mixed-methods study. SUBJECTS AND
      SETTING: The study setting was 2 LTC facilities in the Midwestern United States.
      The sample comprised 39 staff from 2 facilities, including 26 from a high-ITS
      facility and 13 from the low-ITS facility. Respondents included certified nurse
      assistants, certified medical technicians, restorative medical technicians,
      social workers, RNs, licensed practical nurses, information technology staff,
      administrators, and directors. METHODS: This study is a secondary analysis of
      interviews regarding communication and education strategies in 2 LTC agencies.
      This analysis focused on focus group interviews, which included both direct and
      nondirect care providers. RESULTS: Eight themes (codes) were identified in the
      analysis. Three themes are presented individually with exemplars of communication
      and education strategies. The analysis revealed specific differences between the
      high-ITS and low-ITS facilities in regard to education and communication
      involving pressure ulcer prevention. These differences have direct implications
      for WOC nurses consulting in the LTC setting. CONCLUSIONS: Findings from this
      study suggest that effective strategies for staff education and communication
      regarding PU prevention differ based on the level of ITS within a given facility.
      Specific strategies for education and communication are suggested for agencies
      with high ITS and agencies with low ITS.

PMID- 25945823
TI  - Risk factors associated with heel pressure ulcers in hospitalized patients.
AB  - PURPOSE: To develop and validate a method of predicting whether patients will
      develop a heel pressure ulcer during their hospital stay. DESIGN: This
      retrospective case-control study used 2 separate data sets, one for an initial
      analysis followed by a second data set for validation analysis. SUBJECTS AND
      SETTING: From 2009 to 2011, medical records of discharged patients with a DRG
      code for heel pressure ulcers in our urban, tertiary medical center were
      retrospectively reviewed. Using age as the matching criterion, we then reviewed
      cases of patients without heel pressure ulcers. The initial analysis comprised 37
      patients with hospital-acquired heel pressure ulcers and 300 without. The
      validation analysis included 12 patients with heel pressure ulcers and 68
      without. METHOD: In order to develop this method of identifying patients with
      heel pressure ulcers, logistic regression modeling was used to select a set of
      patient characteristics and hospital conditions that, independently and in
      combination, predicted heel pressure ulcers. Logistic modeling produced adjusted
      and unadjusted odds ratios for each of the significant predictor variables. The
      validation analysis was employed to test the predictive accuracy of the final
      model. RESULTS: Initial analysis revealed 4 significant and independent
      predictors for heel pressure ulcer formation during hospitalization: diabetes
      mellitus, vascular disease, immobility, and an admission Braden Scale score of 18
      or less. These findings were also supported in the validation analysis.
      CONCLUSION: Beyond a risk assessment scale, staff should consider other factors
      that can predispose a patient to heel pressure ulcer development during their
      hospital stay, such as comorbid conditions (diabetes mellitus and vascular
      disease) and immobility.

PMID- 25945824
TI  - Health-related quality of life in persons living with a urostomy.
AB  - PURPOSE: The purpose of the study was to determine the life experiences and
      health-related quality of life (HRQOL) of patients living with a urostomy.
      DESIGN: Cross-sectional descriptive study. SUBJECTS AND SETTING: This prospective
      and descriptive study was carried out in a research and training hospital in
      Gaziantep, Turkey; data were collected from May 2009 to September 2011. Twenty
      four participants had undergone a urostomy operation at least 4 months before
      study participation. METHODS: A form querying pertinent demographic and clinical
      information, combined with the European Organization for Research and Treatment
      of Cancer Quality of Life Questionnaire (EORTC QoL Q-C30) was used for data
      collection. Data collection forms were sent to the patients via mail in closed
      envelopes. The Mann-Whitney U, the Kruskal Wallis, and Wilcoxon signed rank tests
      were used for the comparative statistics; statistical significance was accepted
      when P values were <.05. RESULTS: The mean age of the 24 participants was 63.45
      +/- 6.33 years (mean +/- SD; range, 49-72 years). The average time since surgery
      was 9.83 +/- 2.34 months (range, 4-18 months). Most respondents stated that their
      urostomy affected their dressing habits (83.4%), sleep patterns (91.7%), family
      life (91.7%), participation in social activities (91.7%), and occupation (75.0%).
      All participants reported problems with psychological health and sexual activity
      following urostomy surgery. Analysis of EORTC QoLQ-C3 scores revealed that
      general wellness, functional condition, and symptomatic condition mean scores
      were lower than population-based norms associated with this instrument (54.16 +/-
      15.29, 44.07 +/- 9.62, and 64.31 +/- 12.56, respectively). CONCLUSIONS: Creation
      of a urostomy affected the patients' lifestyle and HRQOL negatively. Determining
      the patients' experiences, problems, and the change in HRQOL may provide
      assistance in designing appropriate nursing approaches to alleviate problems
      adapting to a urostomy.

PMID- 25945825
TI  - Prevalence of dependent loops in urinary drainage systems in hospitalized
      patients.
AB  - PURPOSE: The purpose of this study was to measure the prevalence and
      configuration of dependent loops in urinary drainage systems in hospitalized,
      catheterized adults. SUBJECTS: The study sample comprised 141 patients with
      indwelling urinary catheters; subjects were hospitalized at an academic health
      center in northern Florida. METHODS: We measured the prevalence of dependent
      loops in urine drainage systems and the incidence of urine-filled dependent loops
      over a 3-week period. We measured the heights of the crest (H(c)), trough (H(t)),
      and, when urine-filled dependent loops were present, the patient-side (H(p)) and
      bag-side (H(b)) menisci with a laser measurement system. All variables were
      measured in centimeters. RESULTS: The majority of observed urine drainage systems
      (85%) contained dependent loops in the drainage tubing and 93.8% of the dependent
      loops contained urine. H(c) and H(t) averaged 45.1 +/- 11.1 and 27 +/- 16.7 cm,
      respectively. Meniscus height difference (H(b) - H(p)) averaged 8.2 +/- 5.8 and 
      12.2 +/- 9.9 cm when H(p) < H(b)(65.3%) and H(p) > H(b) (32.7%), respectively.
      CONCLUSIONS: We found that dependent loops are extremely common in urinary
      drainage systems among hospitalized patients despite the manufacturer
      recommendations and nursing and hospital policies. Maintaining the urine drainage
      tubing free of dependent loops would require incorporation into nursing care
      priorities and workflow as inadvertent force on the tubing, for example, patient
      movement or nurse contact can change tubing configuration and allow excess
      drainage tubing to re-form a dependent loop.

PMID- 25945827
TI  - The advance practice exam: understanding the 7 domains of advanced practice
      nursing.

PMID- 25945826
TI  - Randomized controlled study of the effects of 2 fecal management systems on
      incidence of anal erosion.
AB  - PURPOSE: To compare the incidence of anal erosion between 2 indwelling fecal
      management systems. Anal erosion was defined as localized mucous membrane tissue
      impairments of the anal canal caused by corrosive fecal enzymes and/or indwelling
      devices. DESIGN: Randomized comparative effectiveness clinical trial comparing 2
      commercially available indwelling fecal management systems. SUBJECTS AND SETTING:
      The target population was adults cared for on medical, surgical, and neurological
      intensive care units (ICUs) and non-ICU units with an order for indwelling fecal
      management system placement. The research setting was a 1200-bed quaternary-care
      medical center in the Midwestern United States. Seventy-nine patients
      participated in the study; 41 received system A and 38 received system B.
      Subjects' mean age was 64 +/- 13.6 years (mean +/- SD), and 52% were female.
      METHODS: Nurse researchers inserted 1 of 2 indwelling fecal management systems
      and assessed patients daily for anal erosion. Data were collected on patient
      demographics, medical history and insertion date, reason for the fecal management
      system, volume of water in balloon and balloon pressure daily, diet, body mass
      index, ease of insertion and removal, amount of resistance, and when and why the
      device was removed. Anecdotal comments from front-line staff nurses were also
      recorded. Occurrences of anal ulcer or erosion was compared using logistic
      regression models that adjusted for length of system use and time to event using
      Kaplan-Meier estimates and log rank tests. RESULTS: The incidence of anal erosion
      was 12.7%. There were no differences in incidence of anal erosions between the 2
      groups (12.2% vs 13.2% for systems A and B, respectively, P = .88), or in time to
      development of the erosions (P = .82). Leakage of stool occurred in 70% of
      patients and was associated with anal erosion (P = .027). CONCLUSIONS: In this
      randomized comparative effectiveness research study, there was no difference in
      the incidence of anal erosion between groups. Purchasing decisions cannot be made
      based on differences in general product characteristics postulated to influence
      likelihood of anal erosion. Results regarding balloon water volume, mucosa
      pressure generated, and anal erosions require further study.

PMID- 25945828
TI  - Silver-based dressing in an extremely low-birth-weight infant: a case study.
AB  - BACKGROUND: Dressings containing silver have been considered dangerous for
      neonatal patients. Many practitioners are hesitant to place wound applications
      (with or without silver) on premature infants based on the potential risk of
      absorption and toxicity. Few studies have been conducted looking at long-term
      effects of current dressing products in the neonate. CASE: We used a flexible
      polyurethane foam containing ionic silver to treat the skin breakdown in a 23
      week-old infant. CONCLUSION: The silver foam dressing was safely and successfully
      used in the treatment of this extremely low-birth-weight infant with skin
      breakdown.

PMID- 25945831
TI  - Determination of the rat in vivo pharmacokinetic profile of a bone-targeting dual
      action pro-drug for treatment of osteoporosis.
AB  - The in vivo hydrolytic pathway of a dual-function bone-targeting EP4 receptor
      agonist-bisphosphonate pro-drug was deduced from radiolabeling experiments. A
      (14)C labeled pro-drug was used to monitor liberation of the bisphosphonate and
      results were compared to parallel studies where the EP4 receptor agonist was
      labeled with (3)H. The bone-adsorption of the (14)C pro-drug following an IV
      bolus was about 10% compared to 7.8% for the tritiated pro-drug. The difference
      in release half-life (5.2 and 19.7 days from (3)H and (14)C experiments,
      respectively) indicated that, after binding to bone, the initial hydrolysis
      occurred at the ester moiety of the linker releasing the EP4 agonist. The
      conjugate was found to concentrate in more porous, high-surface-area regions of
      the long bones. Both (3)H and (14)C experiments indicated a short circulating
      half-life (1-2 h) in blood. 

PMID- 25945832
TI  - Inhibition of thioredoxin 1 leads to apoptosis in drug-resistant multiple
      myeloma.
AB  - Multiple myeloma (MM) is a hematological malignancy characterized by the aberrant
      accumulation of clonal plasma cells in the bone marrow. Despite recent
      advancement in anti-myeloma treatment, MM remains an incurable disease. This
      study showed higher intrinsic oxidative stress and higher Trx1 and TrxR1 protein
      levels in MM cells compared to normal cells. Drug-induced Trx1 (PX-12) and TrxR1
      (Auranofin) inhibition disrupted redox homeostasis resulting in ROS-induced
      apoptosis in MM cells and a reduction in clonogenic activity. Knockdown of either
      Trx1 or TrxR1 reduced MM cell viability. Trx1 inhibition by PX-12 sensitized MM
      cells to undergo apoptosis in response to the NF-kappabeta inhibitors, BAY 11
      7082 and curcumin. PX-12 treatment decreased the expression of the NF-kappabeta
      subunit p65 in MM cells. Bortezomib-resistant MM cells contained higher Trx1
      protein levels compared to the parental cells and PX-12 treatment resulted in
      apoptosis. Thus, increased Trx1 enhances MM cell growth and survival and exerts
      resistance to NF-kappabeta inhibitors. Therefore inhibiting the thioredoxin
      system may be an effective therapeutic strategy to treat newly diagnosed as well
      as relapsed/refractory MM.

PMID- 25945833
TI  - hERG1/Kv11.1 activation stimulates transcription of p21waf/cip in breast cancer
      cells via a calcineurin-dependent mechanism.
AB  - The function of Kv11.1 is emerging in breast cancer biology, as a growing body of
      evidence indicates that the hERG1/Kv11.1 potassium channel is aberrantly
      expressed in several cancer types including breast cancers.The biological effects
      of Kv11.1 channel blockers and their associated side effects are very well known
      but the potential use of Kv11.1 activators as an anticancer strategy are still
      unexplored. In our previous work, we have established that stimulation of the
      Kv11.1 potassium channel activates a senescent-like program that is characterized
      by a significant increase in tumor suppressor protein levels, such as p21waf/cip
      and p16INK4A. In this study we investigated the mechanism linking Kv11.1
      stimulation to augmentation of p21waf/cip protein level. We have demonstrated
      that the Kv11.1 channel activator NS1643 activates a calcineurin-dependent
      transcription of p21waf/cip and that this event is fundamental for the inhibitory
      effect of NS1643 on cell proliferation. Our results reveal a novel mechanism by
      which stimulation of Kv11.1 channel leads to transcription of a potent tumor
      suppressor and suggest a potential therapeutic use for Kv11.1 channel activators.

PMID- 25945834
TI  - Overexpression of PP2A inhibitor SET oncoprotein is associated with tumor
      progression and poor prognosis in human non-small cell lung cancer.
AB  - SET oncoprotein is an endogenous inhibitor of protein phosphatase 2A (PP2A), and
      SET-mediated PP2A inhibition is an important regulatory mechanism for promoting
      cancer initiation and progression of several types of human leukemia disease.
      However, its potential relevance in solid tumors as non-small cell lung cancer
      (NSCLC) remains mostly unknown. In this study, we showed that SET was evidently
      overexpressed in human NSCLC cell lines and NSCLC tissues. Clinicopathologic
      analysis showed that SET expression was significantly correlated with clinical
      stage (p < 0.001), and lymph node metastasis (p < 0.05). Kaplan-Meier analysis
      revealed that patients with high SET expression had poorer overall survival rates
      than those with low SET expression. Moreover, knockdown of SET in NSCLC cells
      resulted in attenuated proliferative and invasive abilities. The biological
      effect of SET on proliferation and invasion was mediated by the inhibition of the
      PP2A, which in turn, activation of AKT and ERK, increased the expression of
      cyclin D1 and MMP9, and decreased the expression of p27. Furthermore, we observed
      that restoration of PP2A using SET antagonist FTY720 impaired proliferative and
      invasive potential in vitro, as well as inhibited tumor growth in vivo of NSCLC
      cells. Taken together, SET oncoprotein plays an important role in NSCLC
      progression, which could serve as a potential prognosis marker and a novel
      therapeutic target for NSCLC patients. 

PMID- 25945835
TI  - Upregulation of spondin-2 predicts poor survival of colorectal carcinoma
      patients.
AB  - Colorectal cancer (CRC) is the third and second most common cancer in males and
      females worldwide, respectively. Spondin-2 is a conserved secreted extracellular
      matrix protein and a candidate cancer biomarker. Here we found that Spondin-2
      mRNA was upregulated in CRC tissues using quantitative RT-PCR and data-mining of
      public Oncomine microarray datasets. Spondin-2 protein was increased in CRC
      tissues, as revealed by immunohistochemistry analyses of two tissue microarrays
      containing 180 cases. Spondin-2 gene expression was significantly associated with
      CRC stage, T stage, M stage and Dukes stage, while its protein was associated
      with age and M stage. Kaplan-Meier analysis revealed that the upregulated Spondin
      2 mRNA and protein predicted poor prognosis of CRC patients. Univariate and
      multivariate Cox regression analyses indicated that grade, recurrence, N stage
      and high Spondin-2 were independent predictors of overall survival of CRC
      patients. ELISA revealed that plasma Spondin-2 was upregulated in CRC and dropped
      after surgery. Receiver operating characteristic curve analysis demonstrated that
      plasma Spondin-2 has superior predictive performance for CRC with an area under
      the curve of 0.959 and the best sensitivity/specificity of 100%/90%. Furthermore,
      ectopic expression of Spondin-2 enhanced colon cancer cell proliferation. Spondin
      2 could be an independent diagnostic and prognostic biomarker of colon cancer. 

PMID- 25945836
TI  - Metabolomic profile of glycolysis and the pentose phosphate pathway identifies
      the central role of glucose-6-phosphate dehydrogenase in clear cell-renal cell
      carcinoma.
AB  - The analysis of cancer metabolome has shown that proliferating tumor cells
      require a large quantities of different nutrients in order to support their high
      rate of proliferation. In this study we analyzed the metabolic profile of
      glycolysis and the pentose phosphate pathway (PPP) in human clear cell-renal cell
      carcinoma (ccRCC) and evaluate the role of these pathways in sustaining cell
      proliferation, maintenance of NADPH levels, and production of reactive oxygen
      species (ROS). Metabolomic analysis showed a clear signature of increased glucose
      uptake and utilization in ccRCC tumor samples. Elevated levels of glucose-6
      phosphate dehydrogenase (G6PDH) in association with higher levels of PPP-derived
      metabolites, suggested a prominent role of this pathway in RCC-associated
      metabolic alterations. G6PDH inhibition, caused a significant decrease in cancer
      cell survival, a decrease in NADPH levels, and an increased production of ROS,
      suggesting that the PPP plays an important role in the regulation of ccRCC redox
      homeostasis. Patients with high levels of glycolytic enzymes had reduced
      progression-free and cancer-specific survivals as compared to subjects with low
      levels. Our data suggest that oncogenic signaling pathways may promote ccRCC
      through rerouting the sugar metabolism. Blocking the flux through this pathway
      may serve as a novel therapeutic target. 

PMID- 25945837
TI  - Insulin-like growth factor binding protein-3 inhibits cell adhesion via
      suppression of integrin beta4 expression.
AB  - We previously reported that IGF binding protein-3 (IGFBP-3), a major IGF-binding
      protein in human serum, regulates angiogenic activities of human head and neck
      squamous cell carcinoma (HNSCC) cells and human umbilical vein endothelial cells
      (HUVECs) through IGF-dependent and IGF-independent mechanisms. However, the role
      of IGFBP-3 in cell adhesion is largely unknown. We demonstrate here that IGFBP-3
      inhibits the adhesion of HNSCC cells and HUVECs to the extracellular matrix
      (ECM). IGFBP-3 reduced transcription of a variety of integrins, especially
      integrin beta4, and suppressed phosphorylation of focal adhesion kinase (FAK) and
      Src in these cells through both IGF-dependent and IGF-independent pathways. IGFBP
      3 was found to suppress the transcription of c-fos and c-jun and the activity of
      AP1 transcription factor. The regulatory effect of IGFBP-3 on integrin beta4
      transcription was attenuated by blocking c-jun and c-fos gene expression via
      siRNA transfection. Taken together, our data show that IGFBP-3 has IGF-dependent
      and -independent inhibitory effects on intracellular adhesion signaling in HNSCC
      and HUVECs through its ability to block c-jun and c-fos transcription and thus AP
      1-mediated integrin beta4 transcription. Collectively, our data suggest that
      IGFPB-3 may be an effective cancer therapeutic agent by blocking integrin
      mediated adhesive activity of tumor and vascular endothelial cells. 

PMID- 25945838
TI  - Accelerated hepatocellular carcinoma development in CUL4B transgenic mice.
AB  - Cullin 4B (CUL4B) is a component of the Cullin 4B-Ring E3 ligase (CRL4B) complex
      that functions in proteolysis and in epigenetic regulation. CUL4B possesses tumor
      promoting properties and is markedly upregulated in many types of human cancers.
      To determine the role of CUL4B in liver tumorigenesis, we generated transgenic
      mice that expressed human CUL4B in livers and other tissues and evaluated the
      development of spontaneous and chemically-induced hepatocellular carcinomas. We
      observed that CUL4B transgenic mice spontaneously developed liver tumors at a
      high incidence at old ages and exhibited enhanced DEN-induced
      hepatocarcinogenesis. There was a high proliferation rate in the livers of CUL4B
      transgenic mice that was accompanied by increased levels of Cdk1, Cdk4 and cyclin
      D1 and decreased level of p16. The transgenic mice also exhibited increased
      compensatory proliferation after DEN-induced liver injury, which was accompanied
      by activation of Akt, Erk, p38 and NF-kappaB. We also found that Prdx3 was
      downregulated and that DEN induced a higher level of reactive oxygen species in
      the livers of transgenic mice. Together, our results demonstrate a critical role
      of CUL4B in hepatocarcinogenesis in mice. 

PMID- 25945839
TI  - Torin2 targets dysregulated pathways in anaplastic thyroid cancer and inhibits
      tumor growth and metastasis.
AB  - Anaplastic thyroid cancer (ATC) is rare but it is one of the most lethal human
      malignancies with no effective therapy. There is a pressing need to identify new
      therapeutic agents for ATC. We performed quantitative high-throughput screening
      (qHTS) in ATC cell lines using a compound library of 3,282 drugs. qHTS identified
      100 pan-active agents. Enrichment analysis of qHTS data showed drugs targeting
      mTOR were one of the most active drug categories, and Torin2 showed the highest
      efficacy. We found mTOR to be upregulated in ATC. Treatment of multiple ATC cell
      lines with Torin2 showed significant dose-dependent inhibition of cellular
      proliferation with caspase-dependent apoptosis and G1/S phase arrest. Torin2
      inhibited cellular migration and inhibited the phosphorylation of key effectors
      of the mTOR-pathway (AKT, 4E-BP1 and 70S6K), as well as claspin and survivin
      expression, regulators of cell cycle and apoptosis. In our in vivo mouse model of
      metastatic ATC, Torin2 inhibited tumor growth and metastasis and significantly
      prolonged overall survival. Our findings suggest that Torin2 is a promising agent
      for ATC therapy and that it effectively targets upregulated pathways in human
      ATC.

PMID- 25945842
TI  - Simultaneous production and separation of biohydrogen in mixed culture systems by
      continuous dark fermentation.
AB  - Hydrogen production by dark fermentation is one promising technology. However,
      there are challenges in improving the performance and efficiency of the process.
      The important factors that must be considered to obtain a suitable process are
      the source of the inoculum and its pre-treatment, types of substrates, the
      reactor configurations and the hydrogen partial pressure. Furthermore, to obtain
      high-quality hydrogen, it is necessary to integrate an effective separation
      procedure that is compatible with the intrinsic characteristics of a biological
      process. Recent studies have suggested that a stable and robust process could be
      established if there was an effective selection of a mixed microbial consortium
      with metabolic pathways directly targeted to high hydrogen yields. Additionally,
      the integration of membrane technology for the extraction and separation of the
      hydrogen produced has advantages for the upgrading step, because this technology
      could play an important role in reducing the negative effect of the hydrogen
      partial pressure. Using this technology, it has been possible to implement a
      production-purification system, the 'hydrogen-extractive membrane bioreactor'.
      This configuration has great potential for direct applications, such as fuel
      cells, but studies of new membrane materials, module designs and reactor
      configurations are required to achieve higher separation efficiencies. 

PMID- 25945840
TI  - Polyphenol-rich extract of Pimenta dioica berries (Allspice) kills breast cancer
      cells by autophagy and delays growth of triple negative breast cancer in athymic
      mice.
AB  - Bioactive compounds from edible plants have limited efficacy in treating advanced
      cancers, but they have potential to increase the efficacy of chemotherapy drugs
      in a combined treatment. An aqueous extract of berries of Pimenta dioica
      (Allspice) shows promise as one such candidate for combination therapy or
      chemoprevention. An aqueous extract of Allspice (AAE) was tested against human
      breast cancer (BrCa) cells in vitro and in vivo. AAE reduced the viability and
      clonogenic growth of several types of BrCa cells (IC50 <= 100 MUg/ml) with
      limited toxicity in non-tumorigenic, quiescent cells (IC50 >200 MUg/ml). AAE
      induced cytotoxicity in BrCa was inconsistent with apoptosis, but was associated
      with increased levels of autophagy markers LC3B and LC3B-positive puncta.
      Silencing the expression of autophagy related genes (ATGs) prevented AAE-induced
      cell death. Further, AAE caused inhibition of Akt/mTOR signaling, and showed
      enhanced cytotoxicity when combined with rapamycin, a chemotherapy drug and an
      inhibitor of mTOR signaling. Oral administration (gavage) of AAE into athymic
      mice implanted with MDA-MB231 tumors inhibited tumor growth slightly but not
      significantly (mean decrease ~ 14%, p >= 0.20) if mice were gavaged post-tumor
      implant. Tumor growth showed a significant delay (38%) in tumor palpability and
      growth rate (time to reach tumor volume >= 1,000 mm3) when mice were pre-dosed
      with AAE for two weeks. Analysis of tumor tissues showed increased levels of LC3B
      in AAE treated tumors, indicating elevated autophagic tumor cell death in vivo in
      treated mice. These results demonstrate antitumor and chemo-preventive activity
      of AAE against BrCa and potential for adjuvant to mTOR inhibition.

PMID- 25945841
TI  - MiR-338-3p inhibits epithelial-mesenchymal transition in gastric cancer cells by
      targeting ZEB2 and MACC1/Met/Akt signaling.
AB  - MicroRNAs (miRNAs) are involved in the epithelial-mesenchymal transition (EMT)
      process and are associated with metastasis in gastric cancer (GC). MiR-338-3p has
      been reported to be aberrantly expressed in GC. In the present study, we show
      that miR-338-3p inhibited the migration and invasion of GC cells in vitro.
      Knocking down miR-338-3p in GC cells led to mesenchymal-like changes. MiR-338-3p
      influenced the expression of the EMT-associated proteins by upregulating the
      epithelial marker E-cadherin and downregulating the mesenchymal markers, N
      cadherin, fibronectin, and vimentin. In terms of mechanism, miR-338-3p directly
      targeted zinc finger E-box-binding protein 2 (ZEB2) and metastasis-associated in
      colon cancer-1 (MACC1). MiR-338-3p repressed the Met/Akt pathway after MACC1
      inhibition. Reintroduction of ZEB2 and MACC1 reversed miR-338-3p-induced EMT
      suppression. Consistently, inverse correlations were also observed between the
      expression of miR-338-3p and ZEB2 or MACC1 in human GC tissue samples. In
      conclusion, miR-338-3p inhibited the EMT progression in GC cells by targeting
      ZEB2 and MACC1/Met/Akt signaling. 

PMID- 25945843
TI  - Economic assessment of sludge handling and environmental impact of sludge
      treatment in a reed bed system.
AB  - The effect on the environment of the establishment and operation of a sludge
      treatment reed bed system (STRB) is quite limited compared to mechanical sludge
      dewatering, with its accompanying use of energy and chemicals. The assessment
      presented here of the investment, operation and maintenance costs of a typical
      STRB, and of the related environmental impact, is based on the experiences gained
      from the operation of a large number of STRB in Denmark. There are differences in
      the environmental perspectives and costs involved in mechanical sludge dewatering
      and disposal on agricultural land compared to STRB. The two treatment methods
      were considered for comparison based on a treatment capacity of 550 tons of dry
      solids per year and with land application of the biosolids in Denmark. The
      initial capital cost for STRB is higher than a conventional mechanical system;
      however, an STRB would provide significant power and operating-cost savings, with
      a significant saving in the overall cost of the plant over 20-30 years. The
      assessment focuses on the use of chemicals, energy and greenhouse gas emissions
      and includes emptying, sludge residue quality and recycling. STRB with direct
      land application is the most cost-effective scenario and has the lowest
      environmental impact. A sludge strategy consisting of an STRB will be
      approximately DKK 536,894-647,636 cheaper per year than the option consisting of
      a new screw press or decanter. 

PMID- 25945844
TI  - Application of novel consortium TSR for treatment of industrial dye manufacturing
      effluent with concurrent removal of ADMI, COD, heavy metals and toxicity.
AB  - The present study was aimed towards the effective bio-treatment of actual
      industrial effluent containing as high as 42,000 mg/L COD (chemical oxygen
      demand), >28,000 ADMI (American Dye Manufacturers Institute) color value and four
      heavy metals using indigenous developed bacterial consortium TSR. Mineral salt
      medium supplemented with as low as 0.02% (w/v) yeast extract and glucose was
      found to remove 70% ADMI, 69% COD and >99% sorption of heavy metals in 24 h from
      the effluent by consortium TSR. The biodegradation of effluent was monitored by
      UV-vis light, HPLC (high performance liquid chromatography), HPTLC (high
      performance thin layer chromotography) and FTIR (Fourier transform infrared
      spectroscopy) and showed significant differences in spectra of untreated and
      treated effluent, confirming degradation of the effluent. Induction of
      intracellular azoreductase (107%) and NADH-DCIP reductase (128%) in addition to
      extracellular laccase (489%) indicates the vital role of the consortium TSR in
      the degradation process. Toxicity study of the effluent using Allium cepa by
      single cell gel electrophoresis showed detoxification of the effluent. Ninety per
      cent germination of plant seeds, Triticum aestivum and Phaseolus mungo, was
      achieved after treatment by consortium TSR in contrast to only 20% and 30%
      germination of the respective plants in case of untreated effluent. 

PMID- 25945845
TI  - The influence of geometrical characteristics on the photocatalytic activity of
      TiO2 nanotube arrays for degradation of refractory organic pollutants in
      wastewater.
AB  - The effects of geometrical characteristics such as surface area (SA) and porosity
      of TiO2 nanotube arrays (TNAs) on its photocatalytic activity were investigated
      by applying variable voltages and reaction times for the anodization of Ti
      substrates. While larger SA of nanotubes was observed under higher applied
      potential, the porosity of TNAs decreased by increasing anodizing voltage. Under
      applied potential of 80 V, the SA of TNAs increased from 0.164 to 0.471 m2/g as
      anodization time increased from 1 to 5 hours, respectively. However, no
      significant effect on the porosity of TNAs was observed. On the other hand, both
      SA and porosity of TNAs, synthesized at 60 V, increased by augmenting the
      anodization time from 1 to 3 hours. But further increasing of anodization time to
      5 hours resulted in a decreased SA of TNAs with no effect on their porosity.
      Accordingly, the TNAs with SA of 0.368 m2/g and porosity of 47% showed the
      highest photocatalytic activity for degradation of 4-chlorobenzoic acid (4CBA).
      Finally, the degradation of refractory model compounds such as carbamazepine and
      bisphenol-A was tested and more than 50% of both compounds could be degraded
      under UV-A irradiation (lambdamax=365 nm).

PMID- 25945846
TI  - Magnesium hydroxide coagulation performance and floc properties in treating high
      pH reactive orange wastewater.
AB  - Application of magnesium hydroxide as a coagulant for treating high pH reactive
      orange wastewater was studied. The coagulation performance and magnesium
      hydroxide-reactive orange floc properties were investigated under different
      dosages, feeding modes and pH values. Flocculation index (FI) was then discussed
      with controlled experiments using an intelligent particle dispersion analyzer and
      optimum coagulant dose of 150 mg/L (magnesium ion) was obtained for pH value 12.
      The results showed that the optimum magnesium ion dose tended to decrease with
      the increase of initial pH value. One time addition feeding mode led to
      relatively large FI value and higher removal efficiency compared with other
      addition modes. All of the flocs under investigation showed a limited capacity
      for re-growth when they had been previously broken. Based on the changes of zeta
      potential and floc properties, charge neutralization and precipitate enmeshment
      were proposed to be the main coagulation mechanisms. 

PMID- 25945847
TI  - Performance evaluation of wastewater treatment using horizontal subsurface flow
      constructed wetlands optimized by micro-aeration and substrate selection.
AB  - The effects of micro-aeration and substrate selection on domestic sewage
      treatment performance were explored using three pairs (with or without micro
      aeration) of horizontal subsurface flow (HSSF) constructed wetlands (CWs) filled
      with zeolite, ceramsite or quartz granules. The individual and combined effects
      of micro-aeration and substrate selection on the purification performance of the
      experimental-scale HSSF CWs were evaluated. The results showed that micro
      aeration significantly increased the treatment efficiencies for chemical oxygen
      demand, total nitrogen, total phosphorus (TP), ortho-phosphate (PO4(3-)-P) and
      ammonium nitrogen (NH4+-N) using HSSF CWs, while the substrate selection
      significantly affected the TP, PO4(3-)-P and NH4+-N removal efficiencies
      (p<0.05). A two-way analysis of variance (ANOVA) indicated that there was a
      significant interaction term (i.e. micro-aeration*substrate selection) for NH4+-N
      removal (p<0.05). Among the three substrates, ceramsite was the best substrate
      for the treatment of domestic sewage using HSSF CWs. Therefore, the results of
      this study suggest that a ceramsite-filled HSSF CW with micro-aeration could be
      the optimal configuration for decentralized domestic sewage treatment.

PMID- 25945848
TI  - A comparison of two infiltration models applied to simulation of overland flow
      over a two-dimensional flume.
AB  - At the hillslope scale, where the rill-interrill configuration plays a
      significant role, infiltration is one of the major hydrologic processes affecting
      the generation of overland flow. As such, it is important to achieve a good
      understanding and accurate modelling of this process. Horton's infiltration has
      been widely used in many hydrologic models, though it has been occasionally found
      limited in handling adequately the antecedent moisture conditions (AMC) of soil.
      Holtan's model, conversely, is thought to be able to provide better estimation of
      infiltration rates as it can directly account for initial soil water content in
      its formulation. In this study, the Holtan model is coupled to an existing
      overland flow model, originally using Horton's model to account for infiltration,
      in an attempt to improve the prediction of runoff. For calibration and
      validation, experimental data from a two-dimensional flume which is incorporated
      with hillslope configuration have been used. Calibration and validation results
      showed that Holtan's model was able to improve the modelling results with better
      performance statistics than the Horton-coupled model. Holtan's infiltration
      equation, which allows accounting for AMC, provided an advantage and resulted in
      better runoff prediction of the model. 

PMID- 25945849
TI  - Treatment performances of French constructed wetlands: results from a database
      collected over the last 30 years.
AB  - Approximately 3,500 constructed wetlands (CWs) provide raw wastewater treatment
      in France for small communities (<5,000 people equivalent). Built during the past
      30 years, most consist of two vertical flow constructed wetlands (VFCWs) in
      series (stages). Many configurations exist, with systems associated with
      horizontal flow filters or waste stabilization ponds, vertical flow with
      recirculation, partially saturated systems, etc. A database analyzed 10 years
      earlier on the classical French system summarized the global performances data.
      This paper provides a similar analysis of performance data from 415 full-scale
      two-stage VFCWs from an improved database expanded by monitoring data available
      from Irstea and the French technical department. Trends presented in the first
      study are confirmed, exhibiting high chemical oxygen demand (COD), total
      suspended solids (TSS) and total Kjeldahl nitrogen (TKN) removal rates (87%, 93%
      and 84%, respectively). Typical concentrations at the second-stage outlet are 74
      mgCOD L(-1), 17 mgTSS L(-1) and 11 mgTKN L(-1). Pollutant removal performances
      are summarized in relation to the loads applied at the first treatment stage.
      While COD and TSS removal rates remain stable over the range of applied loads,
      the spreading of TKN removal rates increases as applied loads increase. 

PMID- 25945850
TI  - Heterogeneous oxidation of diclofenac in the presence of alpha-MnO2 nanorods:
      influence of operating factors and mechanism.
AB  - Diclofenac (DCF), one of the pharmaceutical and personal care products that has
      been widely detected in water, was selected as a model pollutant to evaluate the
      oxidation activity of alpha-MnO2 nanorods. The results showed that the
      heterogeneous oxidation process is highly pH dependent, with higher degradation
      efficiency at lower pH values. The complete removal of DCF was obtained within 80
      min at the solution pH value of 2.5. The oxidation kinetics of DCF can be modeled
      by Langmuir-Hinshelwood equation (R2>0.999). The effects of various operating
      parameters, including initial solution pH, alpha-MnO2 dosage, anions, and
      cations, on the oxidation efficiency were investigated in detail. A possible
      reaction pathway for DCF was proposed. In addition, it was demonstrated that the
      alpha-MnO2 nanorods can be recycled without decreasing their oxidation activity
      after 10 cycles.

PMID- 25945851
TI  - Paraquat adsorption on NaX and Al-MCM-41.
AB  - The aim of this work is to determine paraquat adsorption capacity of zeolite NaX
      and Al-MCM-41. All adsorbents were synthesized by hydrothermal method using rice
      husk silica. For Al-MCM-41, aluminum (Al) was added to the synthesis gel of MCM
      41 with Al content of 10, 15, 20 and 25 wt%. The faujasite framework type of NaX
      and mesoporous characteristic of Al-MCM-41 were confirmed by X-ray diffraction.
      Surface area of all adsorbents determined by N2 adsorption-desorption analysis
      was higher than 650 m2/g. Al content and geometry were determined by X-ray
      fluorescence and 27Al nuclear magnetic resonance, respectively. Morphology of Al
      MCM-41 were studied by transmission electron microscopy; macropores and defects
      were observed. The paraquat adsorption experiments were conducted using a
      concentration range of 80-720 mg/L for NaX and 80-560 mg/L for Al-MCM-41. The
      paraquat adsorption isotherms from all adsorbents fit well with the Langmuir
      model. The adsorption capacity of NaX was 120 mg/g-adsorbent. Regarding Al-MCM
      41, the 10% Al-MCM-41 exhibited the lowest capacity of 52 mg/g-adsorbent while
      the other samples had adsorption capacity of 66 mg/g-adsorbent.

PMID- 25945852
TI  - Filtration effects of zebra mussels on pathogens and total bacterial burden in
      the Odra Lagoon (South Baltic).
AB  - As a result of their mode of filter feeding, zebra mussels (Dreissena polymorpha
      Pall.) have been observed to purify natural water bodies and in vitro. Therefore,
      the possibility of using zebra mussels for water purification was investigated in
      a slightly brackish water body of a large lagoon. In this study, water samples
      were taken above, near and at distance from zebra mussel beds (MB) in the Odra
      Lagoon in North East Germany. Near typical bacterial species like Aeromonas spp.
      pathogenic bacteria with potential relation to hospital wastewater pollution
      (Burkholderia cepacia, Staphylococcus aureus, Weeksella spp.) were detected.
      There were no correlations found between either total bacteria or pathogens and
      distance to MB and no antimicrobial effect of the mussels could be deduced. For
      bioremediation in larger water bodies like lagoons, natural zebra MB do not seem
      to play a major antimicrobial role and the effect of artificial mussel grids
      especially against hospital pathogens should be investigated. 

PMID- 25945853
TI  - Activated charcoal-magnetic nanocomposite for remediation of simulated dye
      polluted wastewater.
AB  - Herein, we report a straightforward way to fabricate activated charcoal-magnetic
      nanocomposite (AC-MNC) by chemical precipitation for the sequestration of
      methylene blue (MB) from a simulated solution. The synthesised nanocomposite was
      characterised by Fourier transform infra-red (FTIR), Brunauer-Emmett-Teller
      (BET), transmission electron microscope (TEM) and vibrating sample magnetometer
      (VSM) techniques. A good uniformity in the spherical AC-MNC particles is observed
      from a TEM image with an average particle size diameter of around 25 nm. AC-MNC
      possesses a specific surface area of 387.28 m2 g(-1) with easy dispersibility and
      magnetic separation. The nanocomposite demonstrates an MB sequestration capacity
      of 147.71 mg g(-1). The high efficiency of the nanocomposite is rationalised on
      the basis of H-bonding and electrostatic interaction between the electropositive
      N-atom of MB and electronegative oxygen-containing functional groups on the
      composite surface. Moreover, the exhausted AC-MNC can be efficiently regenerated
      by microwave irradiation followed by elution with methanol. The renewed
      nanocomposite showed good reusability. Thus, the synthesised AC-MNC proved to be
      an interesting and potential material for the remediation of MB-contaminated
      aqueous solution.

PMID- 25945854
TI  - Removal of diazo dye Direct Red 23 from aqueous solution using zero-valent iron
      nanoparticles immobilized on multi-walled carbon nanotubes.
AB  - The present study immobilized nanoscale zero-valent iron (nZVI) on multi-walled
      carbon nanotubes (MWCNTs) to enhance the reactivity of nZVI and prevent its
      aggregation. This novel composite (nZVI/MWCNT) was characterized by scanning
      electron microscopy and X-ray diffraction. The results showed that nZVI particles
      dispersed on the surface of the MWCNTs. The composite was used to remove the
      diazo dye Direct Red 23 from aqueous solution. The effects of nZVI to MWCNT mass
      ratio, nanocomposite content, solution pH, initial dye concentration and
      temperature were studied. The optimum nZVI/MWCNT mass ratio was 1:3. Batch
      experiments suggest that degradation efficiency decreased as the initial dye
      concentration increased and increased as the nanocomposite content increased,
      decreasing the pH from 8 to 4. The reaction followed a pseudo-first-order model
      under the operational conditions investigated in this study. 

PMID- 25945855
TI  - Advanced oxidation degradation kinetics as a function of ultraviolet LED duty
      cycle.
AB  - Ultraviolet (UV) light emitting diodes (LEDs) may be a viable option as a UV
      light source for advanced oxidation processes (AOPs) utilizing photocatalysts or
      oxidizing agents such as hydrogen peroxide. The effect of UV-LED duty cycle,
      expressed as the percentage of time the LED is powered, was investigated in an
      AOP with hydrogen peroxide, using methylene blue (MB) to assess contaminant
      degradation. The UV-LED AOP degraded the MB at all duty cycles. However,
      adsorption of MB onto the LED emitting surface caused a linear decline in reactor
      performance over time. With regard to the effect of duty cycle, the observed rate
      constant of MB degradation, after being adjusted to account for the duty cycle,
      was greater for 5 and 10% duty cycles than higher duty cycles, providing a value
      approximately 160% higher at 5% duty cycle than continuous operation. This
      increase in adjusted rate constant at low duty cycles, as well as contaminant
      fouling of the LED surface, may impact design and operational considerations for
      pulsed UV-LED AOP systems. 

PMID- 25945856
TI  - The application of removal coefficients for viruses in different wastewater
      treatment processes calculated using stochastic modelling.
AB  - This study proposes that calculating and interpreting removal coefficients (K20)
      for bacteriophages in activated sludge (AS) and trickling filter (TF) systems
      using stochastic modelling may provide important information that may be used to
      estimate the removal of phages in such systems using simplified models. In order
      to achieve this, 14 samples of settled wastewater and post-secondary
      sedimentation wastewater were collected every 2 weeks, over a 6-month period (May
      to November), from two AS and two TF systems situated in southern England.
      Initial results have demonstrated that the removal of somatic coliphages in both
      AS and TF systems is considerably higher than that of F-RNA coliphages, and that
      AS more effectively removes both phage groups than TF. The results have also
      demonstrated that K20 values for phages in AS are higher than in TF, which could
      be justified by the higher removal rates observed in AS and the models assumed
      for both systems. The research provides a suggested framework for calculating and
      predicting removal rates of pathogens and indicator organisms in wastewater
      treatment systems using simplified models in order to support integrated water
      and sanitation safety planning approaches to human health risk management. 

PMID- 25945857
TI  - Remediation of MSW landfill leachate by permeable reactive barrier with
      vegetation.
AB  - This research was conducted to investigate in situ treatment of leachate by pilot
      scale permeable reactive barrier (PRB) with vegetation. Two different types of
      PRB media, with and without the presence of ferric chloride sludge, for the
      removal of pollutants were examined. The composite media of PRB comprised a clay
      and sand mixture of 40:60%w/w (system 1) and a clay, ferric chloride sludge and
      sand mixture of 30:10:60%w/w (system 2). The system was operated at a hydraulic
      loading rate of 0.028 m3/m2.d and hydraulic retention time of 10 days. The
      results showed that the performance of system 2 was better in terms of pollutant
      removal efficiencies, with average biochemical oxygen demand, chemical oxygen
      demand and total Kjeldahl nitrogen removals of 76.1%, 68.5% and 73.5%,
      respectively. Fluorescence excitation-emission matrix analyses of water samples
      and sequential extraction of PRB media suggested the removal of humic substances
      through the formation of iron-organic complex. Greenhouse gas (GHG) emissions
      during the treatment of PRB were 8.2-52.1 mgCH4/m2.d, 69.1-601.8 mgCO2/m2.d and
      0.04-0.99 mgN2O/m2.d. The use of system 2 with vegetation resulted in lower GHG
      emissions. The results show that PRB with vegetation could be used as a primary
      treatment for leachate from closed landfill sites.

PMID- 25945858
TI  - Differences in soluble COD and ammonium when applying ultrasound to primary,
      secondary and mixed sludge.
AB  - Ultrasound treatment is often applied to enhance the anaerobic digestion of
      sludge. Optimal conditions for organic matter solubilisation of primary,
      secondary and mixed sludge were assessed by implementing ultrasound disruption at
      different specific energies (from 3,500 to 21,000 kJ/kgTS). The variation in
      soluble chemical oxygen demand (sCOD) and ammonium nitrogen (NH4+-N) was
      monitored following the treatment, and after a subsequent fermentation (24 h, 37 
      degrees C). The effect of the treatment was clearly more pronounced in secondary
      sludge than in the other types of sludge. Relatively minimal values in solubility
      were found when applying ultrasound at different energies depending on the sludge
      (3,500-7,000 kJ/kgTS in primary sludge and 10,500-14,000 kJ/kgTS in secondary
      sludge). This minimal value was not so noticeable in mixed sludge. The addition
      of inoculum was not required after ultrasound disruption in order to perform the
      subsequent fermentation. After this final stage, no general pattern in terms of
      sCOD was observed. Increases and decreases were conditioned by the coverage of
      the ultrasound irradiation; NH4+-N values increased notably during the
      fermentation.

PMID- 25945859
TI  - Particle removal in a novel sequential mechanical filter system loaded with
      blackwater.
AB  - A novel sequential mechanical filter system was developed as an alternative
      primary treatment method for onsite wastewater treatment. The filter combines
      traditional screening with a novel type of counter-flow filter using wood
      shavings as a biodegradable filter matrix. This study tested the system in a
      batch loading regime simulating high frequency toilet flushing using blackwater
      from a student dormitory. The filter removed 78-85% of suspended solids, 60-80%
      of chemical oxygen demand, and 42-57% of total-P in blackwater, giving a
      retentate with a dry matter content of 13-20%. Data analysis clearly indicated a
      tendency towards higher removal performance with high inlet concentrations,
      hence, the system seems to be most applicable to blackwater or other types of
      wastewater with a high content of suspended solids. 

PMID- 25945860
TI  - Experimental study on non-woven filamentous fibre micro-filter with high
      filtration speed.
AB  - A laboratory study was undertaken to pursue the filter performance of a micro
      filter module employing highly porous fibre media under a high filtration rate
      (>=1,500 m/day), faster than that of any conventional filter process. The effects
      of filtration rate, head loss, raw water turbidity, and filter aid chemicals on
      filter performance were analysed. In spite of the extremely high filtration rate,
      the filter achieved an attractive efficiency, reducing the raw water turbidity by
      over 80%. As with other filter systems, the filter aid used ((polyaluminium
      chloride (PAC)) greatly affected the performance of this particular fibre filter.
      Long-term repetitive runs were additionally carried out to confirm the
      reproducibility of the filter performance. Also, a comparison was carried out
      with other high-rate filter systems which are either being tested for use in
      experimental studies, or are already commercially available. This study reveals
      that the filter performance under a high filtration speed is still attractive
      especially as PAC is used. Due to the high porosity of the fibre, the filter had
      small head loss even though the filtration rate was high. These results ascertain
      that it is possible to operate the filters with high filtration rate achieving
      reliable treatment performance. 

PMID- 25945861
TI  - A study on the effects of ozone dosage on dissolved-ozone flotation (DOF) process
      performance.
AB  - Dissolved-ozone flotation (DOF) is a tertiary wastewater treatment process, which
      combines ozonation and flotation. In this paper, a pilot-scale DOF system fed by
      secondary effluent from a wastewater treatment plant (WWTP) in China was used to
      study the effect of ozone dosage on the DOF process performance. The results show
      that an ozone dosage could affect the DOF performance to a large extent in terms
      of color and organic matter removal as well as disinfection performance. The
      optimal color and organic matter removal was achieved at an ozone dosage of 0.8
      mg/l. For disinfection, significant improvement in performance could be achieved
      only when the organic matter removal was optimal. The optimal ozone dosage of at
      least 1.6 mg/l was put forward, in this case, in order to achieve the optimal
      color, turbidity, organic matter and disinfection performance. 

PMID- 25945862
TI  - Torsemide versus furosemide in heart failure patients: insights from Duke
      University Hospital.
AB  - Furosemide has historically been the primary loop diuretic in heart failure
      patients despite data suggesting potential advantages with torsemide. We used the
      Duke Echocardiography Lab Database to investigate patients admitted with heart
      failure to Duke Hospital from 2000 to 2010 who were discharged on either
      torsemide or furosemide. We described baseline characteristics based on discharge
      diuretic and assessed the relationship with all-cause mortality through 5 years.
      Of 4580 patients, 86% (n = 3955) received furosemide and 14% (n = 625) received
      torsemide. Patients receiving torsemide were more likely to be female and had
      more comorbidities compared with furosemide-treated patients. Survival was worse
      in torsemide-treated patients [5-year Kaplan-Meier estimated survival of 41.4%
      (95% CI: 36.7-46.0) vs. 51.5% (95% CI: 49.8-53.1)]. After risk adjustment,
      torsemide use was no longer associated with increased mortality (hazard ratio
      1.16; 95% CI: 0.98-1.38; P = 0.0864). Prospective trials are needed to
      investigate the effect of torsemide versus furosemide because of the potential
      for residual confounding. 

PMID- 25945863
TI  - Phloretin Inhibits Platelet-derived Growth Factor-BB-induced Rat Aortic Smooth
      Muscle Cell Proliferation, Migration, and Neointimal Formation After Carotid
      Injury.
AB  - Abnormal vascular smooth muscle cell proliferation and migration are key factors
      in many cardiovascular diseases. Here, we investigated the effects of phloretin
      on platelet-derived growth factor homodimer (PDGF-BB)-induced rat aortic smooth
      muscle cell (RASMC) proliferation, migration, and neointimal formation after
      carotid injury. Phloretin significantly inhibited the PDGF-BB-stimulated RASMC
      proliferation in a concentration-dependent manner (10-100 MUM). Also, PDGF-BB
      stimulated RASMC migration was inhibited by phloretin at 50 MUM. Pretreating
      RASMC with phloretin dose-dependently inhibited PDGF-BB-induced Akt and p38
      mitogen-activated protein kinases activation. Furthermore, phloretin increased
      p27 and decreased cyclin-dependent kinase 2, CDK4 expression, and p-Rb activation
      in PDGF-BB-stimulated RASMC in a concentration-dependent manner (10-50 MUM). PDGF
      BB-induced cell adhesion molecules and matrix metalloproteinase-9 expression were
      blocked by phloretin at 50 MUM. Preincubation with phloretin dose-dependently
      reduced the intracellular reactive oxygen species production. In vivo study
      showed that phloretin (20 mg/kg) significantly reduced neointimal formation 14
      days after carotid injury in rats. Thus, phloretin may have potential as a
      treatment against atherosclerosis and restenosis after vascular injury. 

PMID- 25945864
TI  - Renal Effects of Cyclooxygenase Inhibition When Nitric Oxide Synthesis Is Reduced
      and Angiotensin II Levels Are Enhanced.
AB  - The involvement of both cyclooxygenase (COX) isoforms in regulating renal
      function is well known but their interactions with other regulatory mechanisms,
      such as angiotensin II (Ang II) and nitric oxide (NO), are not well defined. This
      study has evaluated the relative contribution of both COX isoforms in regulating
      renal function when NO synthesis is reduced with and without a simultaneous
      increment in Ang II levels. The renal responses to a nonselective (meclofenamate)
      or a selective COX2 (nimesulide) inhibitor were examined in dogs pretreated with
      L-NAME with or without an intrarenal Ang II infusion. Meclofenamate induced a
      greater (P < 0.05) renal vasoconstriction than nimesulide in dogs pretreated with
      L-NAME. This vasoconstriction seems to be Ang II-dependent because it was reduced
      (P < 0.05) by captopril administration. Meclofenamate also induced a greater (P <
      0.05) renal vasoconstriction than that elicited by nimesulide in dogs with
      reduced NO synthesis and elevated Ang II levels. The renal vasoconstriction
      induced by nimesulide but not that elicited by meclofenamate in dogs pretreated
      with L-NAME and Ang II, decreased (P < 0.05) during an extracellular volume
      expansion. These results demonstrate that the nonselective COX inhibition induces
      a greater renal vasoconstriction than that elicited by the selective COX2
      inhibition when NO synthesis is reduced, and when NO synthesis is reduced and Ang
      II levels are elevated. 

PMID- 25945865
TI  - Effect of Carvedilol on Serum Heart-type Fatty Acid-binding Protein, Brain
      Natriuretic Peptide, and Cardiac Function in Patients With Chronic Heart Failure.
AB  - OBJECTIVE: To observe the changes of serum heart-type fatty acid-binding protein
      (h-FABP) and brain natriuretic peptide (BNP) in children with chronic heart
      failure (CHF) and evaluate the effects of carvedilol. METHODS: A total of 36
      patients with CHF, including 17 of endocardial fibroelastosis and 19 of dilated
      cardiomyopathy, were enrolled and were randomly divided into a carvedilol
      treatment group (group A) and a conventional treatment group (group B). Group A
      (n = 16) was treated with carvedilol and conventional treatment and group B (n =
      20) was managed with conventional treatment only. Thirty healthy children were
      enrolled as controls. The concentrations of serum h-FABP and BNP were measured by
      enzyme-linked immunosorbent assay, and the left ventricular end-systolic
      diameter, left ventricular end-diastolic diameter, left ventricular ejection
      fraction (LVEF), left ventricular fractional shortening (LVFS), and cardiac index
      (CI) were measured by echocardiography. RESULTS: The concentrations of serum h
      FABP and BNP in patients with CHF were significantly higher than in the control
      group (21.7 +/- 4.3 ng/mL vs. 6.3 +/- 1.7 ng/mL, 582.4 +/- 180.6 pg/mL vs.31.2 +/
      9.8 pg/mL, all P < 0.01), positively correlated with the degree of heart failure
      (all P < 0.01), and were both higher in groups endocardial fibroelastosis and
      dilated cardiomyopathy than in the control group (all P < 0.01), but there was no
      statistically significant difference between the 2 groups (P > 0.05). h-FABP
      concentration in patients with CHF was positively correlated with BNP (r = 0.78,
      P < 0.01) but negatively correlated with LVEF, LVFS, and CI (r = -0.65, -0.64,
      and -0.71, respectively; all P < 0.01). BNP concentration was also negatively
      correlated with LVEF, LVFS, and CI (r = -0.75, -0.61, and -0.79, respectively;
      all P<0.01). After treatment with carvedilol, the serum concentrations of h-FABP
      and BNP in group A were lower than in group B, and the magnitude of heart rate
      reduction, improvement of LVEF, LVFS, and CI, and reduction of left ventricular
      end-systolic diameter and left ventricular end-diastolic diameter in group A were
      all greater than in group B (all P < 0.01). Treatment with carvedilol had no
      adverse events. CONCLUSIONS: Serum concentrations of h-FABP and BNP can be used
      as biomarkers to evaluate the severity of heart failure, and carvedilol can
      significantly improve heart function in children with CHF.

PMID- 25945866
TI  - Nitrogen fixation revisited on iron(0) dinitrogen phosphine complexes.
AB  - A reinvestigation of the treatment of [Fe(N2)(PP)2] (PP = depe, dmpe) with acid
      revealed no ammonium formation. Instead, rapid protonation at the metal center to
      give hydride complexes was observed. Treatment of [Fe(N2)(dmpe)2] with
      methylating agents such as methyl triflate or methyl tosylate resulted in
      methylation of the metal center to afford [FeMe(N2)(dmpe)2](+). Treatment of
      [Fe(N2)(dmpe)2] with trimethylsilyl triflate, however, resulted in reaction at
      dinitrogen affording NH4(+) on subsequent treatment with acid. The side-on bound
      hydrazine complex [Fe(N2H4)(dmpe)2](2+) and bis(ammonia) complex
      [Fe(NH3)2(dmpe)2](2+) were identified by (15)N NMR spectroscopy as other species
      formed in the reaction mixture. 

PMID- 25945867
TI  - Anti-inflammatory Terpenoids from the Leaves and Twigs of Dysoxylum gotadhora.
AB  - Nine new terpenoids (1-3, 5-10), including three cyclolanostane triterpenoids (1
      3) and six isopimarane diterpenoids (5-10), along with six known terpenoids (4,
      11-15), were isolated from the leaves and twigs of Dysoxylum gotadhora. Compound
      1 represents a class of rare natural 21,24-epoxy cyclolanostane-type
      triterpenoids, and compounds 2 and 3 are the first examples of 21,25-epoxy
      cyclolanostane-type triterpenoids. Compounds 1, 2, 4, 8, and 15 exhibited
      noteworthy inhibition of nitric oxide production induced by lipopolysaccharide in
      RAW 264.7 cells with IC50 values of 25.5, 41.5, 27.4, 14.5, and 45.2 MUM,
      respectively. 

PMID- 25945869
TI  - Nanostructural analysis of water distribution in hydrated multicomponent gels
      using thermal analysis and NMR relaxometry.
AB  - Highly complex, multicomponent gels and water-containing soft materials have
      varied applications in biomedical, pharmaceutical, and food sciences, but the
      characterization of these nanostructured materials is extremely challenging. The
      aim of this study was to use stearoyl macrogol-32 glycerides (Gelucire 50/13)
      gels containing seven different species of glycerides, PEG, and PEG-esters, as
      model, complex, multicomponent gels, to investigate the effect of water content
      on the micro- and nanoarchitecture of the gel interior. Thermal analysis and NMR
      relaxometry were used to probe the thermal and diffusional behavior of water
      molecules within the gel network. For the highly concentrated gels (low water
      content), the water activity was significantly lowered due to entrapment in the
      dense gel network. For the gels with intermediate water content, multiple
      populations of water molecules with different thermal responses and diffusion
      behavior were detected, indicating the presence of water in different
      microenvironments. This correlated with the network architecture of the freeze
      dried gels observed using SEM. For the gels with high water content, increased
      quantities of water with similar diffusion characteristics as free water could be
      detected, indicating the presence of large water pockets in these gels. The
      results of this study provide new insights into structure of Gelucire gels, which
      have not been reported before because of the complexity of the material. They
      also demonstrate that the combination of thermal analysis and NMR relaxometry
      offers insights into the structure of soft materials not available by the use of
      each technique alone. However, we also note that in some instances the results of
      these measurements are overinterpreted and we suggest limitations of the methods
      that must be considered when using them. 

PMID- 25945870
TI  - Re: "Risk of ocular blood splatter during oculofacial plastic surgery".

PMID- 25945871
TI  - Reply re: "Risk of Ocular Blood Splatter During Oculofacial Plastic Surgery".

PMID- 25945872
TI  - Re: "Orbital and periorbital extension of congenital dacryocystoceles: suggested
      mechanism and management".

PMID- 25945873
TI  - Reply re: "Orbital and Periorbital Extension of Congenital Dacryocystoceles:
      Suggested Mechanism and Management".

PMID- 25945874
TI  - Re: "Orbital Necrotizing Fasciitis and Osteomyelitis Caused by Arcanobacterium
      haemolyticum: A Case Report".

PMID- 25945875
TI  - Re: "Lower eyelid involutional ectropion repair with lateral tarsal strip and
      internal retractor reattachment with full-thickness eyelid sutures".

PMID- 25945876
TI  - Incomplete punctal canalization: report of Fourier domain optical coherence
      tomography features.

PMID- 25945877
TI  - Re: "Nonsurgical retrieval of retained lacrimal stenting material".

PMID- 25945878
TI  - Subconjunctival fat infiltration complicating autologous fat injection for facial
      augmentation.

PMID- 25945879
TI  - Tumor suppressor genes are larger than apoptosis-effector genes and have more
      regions of active chromatin: Connection to a stochastic paradigm for sequential
      gene expression programs.
AB  - Apoptosis- and proliferation-effector genes are substantially regulated by the
      same transactivators, with E2F-1 and Oct-1 being notable examples. The larger
      proliferation-effector genes have more binding sites for the transactivators that
      regulate both sets of genes, and proliferation-effector genes have more regions
      of active chromatin, i.e, DNase I hypersensitive and histone 3, lysine-4
      trimethylation sites. Thus, the size differences between the 2 classes of genes
      suggest a transcriptional regulation paradigm whereby the accumulation of
      transcription factors that regulate both sets of genes, merely as an aspect of
      stochastic behavior, accumulate first on the larger proliferation-effector gene
      "traps," and then accumulate on the apoptosis effector genes, thereby effecting
      sequential activation of the 2 different gene sets. As IRF-1 and p53 levels
      increase, tumor suppressor proteins are first activated, followed by the
      activation of apoptosis-effector genes, for example during S-phase pausing for
      DNA repair. Tumor suppressor genes are larger than apoptosis-effector genes and
      have more IRF-1 and p53 binding sites, thereby likewise suggesting a paradigm for
      transcription sequencing based on stochastic interactions of transcription
      factors with different gene classes. In this report, using the ENCODE database,
      we determined that tumor suppressor genes have a greater number of open chromatin
      regions and histone 3 lysine-4 trimethylation sites, consistent with the idea
      that a larger gene size can facilitate earlier transcriptional activation via the
      inclusion of more transactivator binding sites. 

PMID- 25945880
TI  - Editorial: in this issue.
AB  - In this issue, we are hosting several reviews on topics of broad interests, such
      as therapeutic or prophylactic antibodies, and the role of autophagy in
      autoimmunity. 

PMID- 25945881
TI  - Say it with proteins: an alphabet of crystal structures.

PMID- 25945882
TI  - A little less leads to lots more.

PMID- 25945883
TI  - Light-driven Na(+) pumps as next-generation inhibitory optogenetic tools.

PMID- 25945884
TI  - A bumpy road for RNA polymerase II.

PMID- 25945885
TI  - Integrin bondage: filamin takes control.

PMID- 25945886
TI  - A molecular syringe that kills cells.

PMID- 25945887
TI  - Dynactin revealed.

PMID- 25945892
TI  - An essential role for chaperone-mediated autophagy in cell cycle progression.
AB  - Hypoxia has long been known to serve as a stimulus for cell cycle arrest. Hypoxia
      mediated cell cycle arrest is mediated through the actions of HIF1alpha (hypoxia
      inducible factor 1, alpha subunit [basic helix-loop-helix transcription factor]),
      which has a nontranscriptional role as an inhibitor of MCM (minichromosome
      maintenance complex component) helicase activity. We identified chaperone
      mediated autophagy as a pathway for selective degradation of HIF1alpha through
      lysosomes prior to the onset of DNA replication. CDK2 (cyclin-dependent kinase 2)
      mediates degradation of HIF1alpha at the G1/S transition, whereas CDK1 (cyclin
      dependent kinase 1) increases HIF1alpha levels and transcriptional activity prior
      to the onset of G1 phase. Lysosomal inhibitors induce cell cycle arrest, which is
      recovered by knockdown of HIF1alpha and EPAS1/HIF2alpha. These findings establish
      lysosomes as essential regulators of cell cycle progression through the
      degradation of HIF1alpha. 

PMID- 25945894
TI  - Surface-hopping dynamics simulations of malachite green: a triphenylmethane dye.
AB  - Malachite green is a typical triphenylmethane dye widely used in fundamental and
      industrial research; however, its excited-state relaxation dynamics remains
      elusive. In this work we simulate its photodynamics from the S2 and S1 states
      using the fewest-switches surface-hopping scheme. In the S2 photodynamics, the
      system first relaxes to the S2 minimum, which immediately hops to the S1 state
      via an S2/S1 conical intersection. In the S1 state, 90% trajectories evolve into
      a structurally symmetric S1 minimum; the remaining ones proceed toward two
      propeller-like S1 minima. Two kinds of S1 minima then decay to the S0 state via
      the S1/S0 conical intersections. The S1 photodynamics is overall similar to the
      S1 excited-state dynamics as a result of the ultrafast S2 -> S1 internal
      conversion in the S2 photodynamics, but the weights of the trajectories that
      decay to the S0 state via three different S1/S0 conical intersections are
      variational. Moreover, the S2 relaxation dynamics mainly happens in a concerted
      synchronous rotation of three phenyl rings. In comparison, in the S1 relaxation
      dynamics, the rotations of two aminophenyl rings can proceed in the same and
      opposite directions. In certain trajectories, only the rotation of an aminophenyl
      ring is active. On the basis of the results, the S2 and S1 excited-state
      lifetimes of malachite green in vacuo are calculated to be 424 fs and 1.2 ps,
      respectively. The present work provides important mechanistic insights for
      similar triphenylmethane dyes. 

PMID- 25945893
TI  - Anamorelin hydrochloride for the treatment of cancer-anorexia-cachexia in NSCLC.
AB  - INTRODUCTION: Cancer anorexia-cachexia syndrome (CACS) is associated with
      increased morbidity and mortality. Anamorelin is a novel, orally active ghrelin
      receptor agonist in clinical development for the treatment of CACS in NSCLC. The
      aim of this review is to summarize preclinical and clinical studies evaluating
      anamorelin as a potential promising treatment for CACS in NSCLC. AREAS COVERED:
      Pharmacodynamics, pharmacokinetics and metabolism, clinical efficacy, safety and
      tolerability of anamorelin for the treatment of CACS in NSCLC were reviewed.
      Anamorelin administration may lead to increases in food intake, body weight and
      lean body mass, and a stimulatory effect on growth hormone secretion in NSCLC
      patients. Anamorelin is well tolerated with no dose-limiting toxicities
      identified to date. EXPERT OPINION: Targeting ghrelin receptors presents the
      advantage of potentially addressing multiple mechanisms of CACS simultaneously
      including appetite, muscle protein balance, adipose tissue metabolism, energy
      expenditure and inflammation. Clinical data suggest that anamorelin is well
      tolerated and it effectively increases appetite, body weight and lean mass in
      patients with advanced NSCLC. Long-term safety remains unknown at this time. The
      potential synergistic effects of anamorelin with nutritional support or exercise
      as well as its efficacy/safety in other tumor types are also unknown.

PMID- 25945896
TI  - GPQuest: A Spectral Library Matching Algorithm for Site-Specific Assignment of
      Tandem Mass Spectra to Intact N-glycopeptides.
AB  - Glycoprotein changes occur in not only protein abundance but also the occupancy
      of each glycosylation site by different glycoforms during biological or
      pathological processes. Recent advances in mass spectrometry instrumentation and
      techniques have facilitated analysis of intact glycopeptides in complex
      biological samples by allowing the users to generate spectra of intact
      glycopeptides with glycans attached to each specific glycosylation site. However,
      assigning these spectra, leading to identification of the glycopeptides, is
      challenging. Here, we report an algorithm, named GPQuest, for site-specific
      identification of intact glycopeptides using higher-energy collisional
      dissociation (HCD) fragmentation of complex samples. In this algorithm, a
      spectral library of glycosite-containing peptides in the sample was built by
      analyzing the isolated glycosite-containing peptides using HCD LC-MS/MS. Spectra
      of intact glycopeptides were selected by using glycan oxonium ions as signature
      ions for glycopeptide spectra. These oxonium-ion-containing spectra were then
      compared with the spectral library generated from glycosite-containing peptides,
      resulting in assignment of each intact glycopeptide MS/MS spectrum to a specific
      glycosite-containing peptide. The glycan occupying each glycosite was determined
      by matching the mass difference between the precursor ion of intact glycopeptide
      and the glycosite-containing peptide to a glycan database. Using GPQuest, we
      analyzed LC-MS/MS spectra of protein extracts from prostate tumor LNCaP cells.
      Without enrichment of glycopeptides from global tryptic peptides and at a false
      discovery rate of 1%, 1008 glycan-containing MS/MS spectra were assigned to 769
      unique intact N-linked glycopeptides, representing 344 N-linked glycosites with
      57 different N-glycans. Spectral library matching using GPQuest assigns the HCD
      LC-MS/MS generated spectra of intact glycopeptides in an automated and high
      throughput manner. Additionally, spectral library matching gives the user the
      possibility of identifying novel or modified glycans on specific glycosites that
      might be missing from the predetermined glycan databases. 

PMID- 25945895
TI  - A brief educational intervention increases providers' human papillomavirus
      vaccine knowledge.
AB  - Recommendation by a healthcare provider is critical to increase human
      papillomavirus (HPV) vaccine uptake in the US. However, current deficits in
      providers' knowledge of HPV and its vaccine are not fully understood and
      interventions to amend knowledge gaps are untested. To determine whether
      attending a structured presentation could increase provider knowledge of the HPV
      vaccine, we assessed knowledge levels of physicians, non-physician healthcare
      workers, and medical students before and after attending a 30-minute lecture held
      between October 2012 and June 2014. Paired t-test and McNemar's test were used to
      compare knowledge scores and the proportion of correct responses for each
      question, respectively. Multiple linear regression analyses were performed to
      examine correlates of baseline knowledge and change in knowledge scores post
      intervention. A total of 427 participants, including 75 physicians, 208 medical
      students, and 144 nurses or other healthcare workers, attended one of 16
      presentations and responded to both pre-test and post-test surveys. Baseline
      knowledge was low among all groups, with scores higher among older participants
      and physicians/medical students. On average, knowledge scores significantly
      improved from 8 to 15 after the presentation (maximum possible score 16) (P <
      .001), irrespective of specialty, race/ethnicity, gender, and age. Although lower
      at baseline, knowledge scores of younger participants and non-physician
      healthcare workers (e.g., nurses, physician assistants (PAs), nursing students)
      improved the most of all groups. We conclude that a brief, structured
      presentation increased HPV knowledge among a variety of healthcare workers, even
      when their baseline knowledge was low. 

PMID- 25945897
TI  - Selective vs Nonselective Nonsteroidal Anti-inflammatory Drugs and Anastomotic
      Leakage After Colorectal Surgery.

PMID- 25945898
TI  - The Danish Organic Action Plan 2020: assessment method and baseline status of
      organic procurement in public kitchens.
AB  - OBJECTIVE: With political support from the Danish Organic Action Plan 2020,
      organic public procurement in Denmark is expected to increase. In order to
      evaluate changes in organic food procurement in Danish public kitchens, reliable
      methods are needed. The present study aimed to compare organic food procurement
      measurements by two methods and to collect and discuss baseline organic food
      procurement measurements from public kitchens participating in the Danish Organic
      Action Plan 2020. DESIGN: Comparison study measuring organic food procurement by
      applying two different methods, one based on the use of procurement invoices (the
      Organic Cuisine Label method) and the other on self-reported procurement (the
      Dogme method). Baseline organic food procurement status was based on organic food
      procurement measurements and background information from public kitchens.
      SETTING: Public kitchens participating in the six organic food conversion
      projects funded by the Danish Organic Action Plan 2020 during 2012 and 2013.
      SUBJECTS: Twenty-six public kitchens (comparison study) and 345 public kitchens
      (baseline organic food procurement status). RESULTS: A high significant
      correlation coefficient was found between the two organic food procurement
      measurement methods (r=0.83, P<0.001) with measurements relevant for the baseline
      status. Mean baseline organic food procurement was found to be 24 % when
      including measurements from both methods. CONCLUSIONS: The results indicate that
      organic food procurement measurements by both methods were valid for the baseline
      status report of the Danish Organic Action Plan 2020. Baseline results in Danish
      public kitchens suggest there is room for more organic as well as sustainable
      public procurement in Denmark.

PMID- 25945899
TI  - Analysis of Physical Collisions in Elite National Rugby League Match Play.
AB  - OBJECTIVE: To investigate the impact forces of collision events during both
      attack and defense in elite rugby league match play and to compare the collision
      profiles between playing positions. PARTICIPANTS: 26 elite rugby league players.
      METHODS: Player collisions were recorded using an integrated accelerometer in
      global positioning system units (SPI-Pro X, GPSports). Impact forces of
      collisions in attack (hit-ups) and defense (tackles) were analyzed from 359 files
      from outside backs (n = 78), adjustables (n = 97), wide-running forwards (n =
      136), and hit-up forwards (n = 48) over 1 National Rugby League season. RESULTS:
      Hit-up forwards were involved in 0.8 collisions/min, significantly more than all
      other positional groups (wide-running forwards P = .050, adjustables P = .042,
      and outside backs P = .000). Outside backs experienced 25% fewer collisions per
      minute than hit-up forwards. Hit-up forwards experienced a collision within the 2
      highest classifications of force (>= 10 g) every 2.5 min of match play compared
      with 1 every 5 and 9 min for adjustables and outside backs, respectively. Hit-up
      forwards performed 0.5 tackles per minute of match play, 5 times that of outside
      backs (ES = 1.90; 95% CI [0.26,3.16]), and 0.2 hit-ups per minute of match play,
      twice as many as adjustables. CONCLUSIONS: During a rugby league match, players
      are exposed to a significant number of collision events. Positional differences
      exist, with hit-up and wide-running forwards experiencing greater collision
      events than adjustables and outside backs. Although these results may be unique
      to the individual team's defensive- and attacking-play strategies, they are
      indicative of the significant collision profiles in professional rugby league.

PMID- 25945900
TI  - Drawing inspiration from children.

PMID- 25945901
TI  - Genetic and Environmental Influences on the Developmental Course of Attention
      Deficit/Hyperactivity Disorder Symptoms From Childhood to Adolescence.
AB  - IMPORTANCE: Attention-deficit/hyperactivity disorder (ADHD) is conceptualized as
      a neurodevelopmental disorder that is strongly heritable. However, to our
      knowledge, no study to date has examined the genetic and environmental influences
      explaining interindividual differences in the developmental course of ADHD
      symptoms from childhood to adolescence (ie, systematic decreases or increases
      with age). The reason ADHD symptoms persist in some children but decline in
      others is an important concern, with implications for prognosis and
      interventions. OBJECTIVE: To assess the proportional impact of genes and the
      environment on interindividual differences in the developmental course of ADHD
      symptom domains of hyperactivity/impulsivity and inattention between ages 8 and
      16 years. DESIGN, SETTING, AND PARTICIPANTS: A prospective sample of 8395 twin
      pairs from the Twins Early Development Study, recruited from population records
      of births in England and Wales between January 1, 1994, and December 31, 1996.
      Data collection at age 8 years took place between November 2002 and November
      2004; data collection at age 16 years took place between February 2011 and
      January 2013. MAIN OUTCOMES AND MEASURES: Both DSM-IV ADHD symptom subscales were
      rated 4 times by participants' mothers. RESULTS: Estimates from latent growth
      curve models indicated that the developmental course of hyperactivity/impulsivity
      symptoms followed a sharp linear decrease (mean score of 6.0 at age 8 years to
      2.9 at age 16 years). Interindividual differences in the linear change in
      hyperactivity/impulsivity were under strong additive genetic influences (81%; 95%
      CI, 73%-88%). More than half of the genetic variation was specific to the
      developmental course and not shared with the baseline level of
      hyperactivity/impulsivity. The linear decrease in inattention symptoms was less
      pronounced (mean score of 5.8 at age 8 years to 4.9 at age 16 years). Nonadditive
      genetic influences accounted for a substantial amount of variation in the
      developmental course of inattention symptoms (54%; 95% CI, 8%-76%), with more
      than half being specific to the developmental course. CONCLUSIONS AND RELEVANCE:
      The large genetic influences on the developmental course of ADHD symptoms are
      mostly specific and independent of those that account for variation in the
      baseline level of symptoms. Different sets of genes may be associated with the
      developmental course vs the baseline level of ADHD symptoms and explain why some
      children remit from ADHD, whereas others persist. Recent longitudinal imaging
      data indicate that the maintenance or increase in symptoms is underpinned by
      atypical trajectories of cortical development. This may reflect a specific
      genetic liability, distinct from that which contributes to baseline ADHD
      symptoms, and warrants closer follow-up.

PMID- 25945902
TI  - [Elevated blood pressure values - rapid therapy adjustment is crucial].

PMID- 25945903
TI  - [Better control of severe community-acquired pneumonia through treatment with
      cortisone].

PMID- 25945904
TI  - [Specific predictors for subsequent interventions after myocardial infarctation].

PMID- 25945905
TI  - [Uricosuric agent benzbromarone vs. allopurinol: comparable effect].

PMID- 25945906
TI  - [56-years old male with unclear dilatation of the right heart].

PMID- 25945907
TI  - [How to do: bile duct ultrasound].
AB  - Grey-scale US of the common bile duct is helpful in detecting the cause of
      biliary obstruction. We describe bile duct anatomy, its implication for
      transducer placement and the process of a systematic US evaluation of normal
      intrahepatic bile ducts and the common bile duct. 

PMID- 25945908
TI  - [Prinzmetal angina after licorice consumption].
AB  - Medical history | We report on a 44-year-old patient with recurrent thoracic pain
      occurring 4 months apart. The patient complained about intense thoracic pain and
      acute dyspnoea in the morning. In the course of the second presentation the
      anamnesis revealed that the previous day the patient had consumed an entire bag
      of licorice (200 g). Investigations | The blood pressure was 90/65 mmHg, heart
      rate 68 beats / min. Neither the performed ECG nor the transthoracic
      echocardiography showed abnormalities. The blood tests revealed elevated troponin
      levels only. No coronary artery stenosis was evident on left heart
      catheterization. After 4 months- the symptoms reappeared- the blood pressure was
      110/50 mmHg. An ECG showed infarct-typical ST elevations. The performed coronary
      angiography showed no stenosis or embolism. Intracoronary nitro administration
      resulted in significant vasodilatation. After 6 hours in the control- ECG the ST
      elevations were missing. We diagnosed a Prinzmetal angina. Treatment and course |
      The patient was given advice not to consume licorice in the future. Her
      medication was adjusted to 2.5 mg amlodipine per day. There has been no further
      presentation with similar symptoms since then. Conclusion | Case reports provide
      evidence of unknown potential side- effects concerning well-known medical plants
      or substances. It is already known that the ingredients of licorice may induce
      hypertension. Potential spastic reactions, such as a Prinzmetal angina, due to
      the possible cardiac effects caused by glycyrrhizin and glycyrrhetinic acid are
      rare side effects of licorice ingestion. 

PMID- 25945909
TI  - [Diabetic foot syndrome - pathogenesis, diagnosis, therapy and prevention].
AB  - The diabetic foot syndrome (DFS) is a complication of diabetes mellitus, implying
      a serious impairment in quality of life for patients in advanced stages of the
      disease. Early detection of risks and stage-appropriate intervention are
      essential to increase the chances of foot salvage. The pathophysiological
      conditions for the formation of a DFS and treatment guidelines are currently
      underestimated. Up to 80 % of amputations are preventable if appropriate
      therapeutic steps were initiated on time in patients with DFS as part of a
      multidisciplinary approach. By proper prevention, the number of patients with DFS
      as well as the risk of recurrent ulcers can be reduced. This CME article gives an
      overview of the pathogenesis, diagnosis, therapy and prevention of DFS. 

PMID- 25945910
TI  - [Inappropriate sinus tachycardia].
AB  - Inappropriate sinus tachycardia is characterized by an unexplained increase of
      the resting sinus rate (> 100 bpm) with excess increase in response to moderate
      activity (mean heart rate > 90 bpm/24 h). Affected patients may suffer from heart
      race, palpitations, fatigue, weakness and dizziness. The mechanisms underlying
      inappropriate sinus tachycardia and its long term prognosis are poorly
      understood. Thus, diagnosis and treatment are empiric and require the initial
      exclusion of potential causes of secondary sinus tachycardia. Therapeutic
      approaches include physical training, beta blockers or ivabradine. Radiofrequency
      catheter ablation should be restricted to patients with refractory and
      longstanding symptoms. 

PMID- 25945911
TI  - [Hyponatremia - a frequent and complex clinical problem].
AB  - Guidelines have become very common in modern medicine. Their primary aim should
      be to provide evidence-based guidance and insight and to help to convey the best
      possible care to patients. As a consequence, guidelines also play a critical role
      in liability issues. Hyponatremia is a frequently encountered condition which is
      considered challenging by many physicians. It is therefore highly appreciated,
      that two interdisciplinary guidelines on hyponatremia have been published
      recently. Unfortunately, the given recommendations differ substantially. Most
      importantly, the roles of existing new and old treatment options are rated
      inconsistently. This demonstrates once again that guidelines never tell the whole
      truth and that we are well advised not to trust them blindly. Given the lack of
      valid evidence from controlled trials, the current guidelines can only offer
      another overview on hyponatremia but they certainly fail to provide clear-cut
      recommendations. The content and controversies of both publications are described
      in this commentary. 

PMID- 25945912
TI  - [Cytomegalovirus after renal transplantation - diagnosis, prevention and
      treatment].

PMID- 25945913
TI  - [How to communicate with patients suffering from dementia].
AB  - The prevalence of patients with cognitive impairment will inevitably increase in
      general hospitals. Communication with these patients is difficult. However, it
      can be improved by implementing organisational measures and behaviour changes of
      the hospital staff. 

PMID- 25945914
TI  - [Hepatitis C in Germany: an analysis of statutory sickness funds claims data].
AB  - BACKGROUND: The aim of this study was to investigate the number of persons who
      obtain medical attention for Hepatitis C Virus (HCV). In addition, we wanted to
      get an overview of the supply situation (frequency and length of therapy or lab
      controls) for patients with HCV infection. METHODOLOGY: Data obtained from
      statutory insurance companies were analyzed. RESULTS: The prevalence of HCV
      diagnosis was 0.19 % within 3 years. Following a positive HCV-test in 19 % of
      patients the diagnosis of acute HCV was documented. In 2008, 9.3 % of patients
      were treated with pegylated Interferon alpha with or without Ribavirin (11.9 %
      for chronic and 3.6 % for acute HCV). A general practitioner initiated in about
      5.1 % and a specialist in 21.7 % of cases a therapy within a year. 37.0 % of
      patients treated by a general practitioner and 57.0 % of patients treated by
      specialists received prescriptions in the third quarter after initiating the
      therapy. Not all patients had a documented test for viral load prior to therapy.
      CONCLUSIONS: 50 % of HCV-patients visited a physician in a 3 year time period
      while an average of 9 % received a therapy within a year. For the coding of acute
      HCV diagnosis, duration of therapy and the necessary viral load test prior
      therapy, the analyses showed deviations from the guideline and differences
      between general practitioners and specialists. For future therapies, patients
      with HCV-infection should be treated in specialized centers so that these
      therapies may develop their efficiency in the health system.

PMID- 25945915
TI  - [The information about discharge medication: what do general practitioners
      need?].
AB  - BACKGROUND: The information about the patient's discharge medication (DM) in the
      discharge letter guarantees the subsequent pharmacotherapy at the interface
      between tertiary to primary care. International data however shows that general
      practitioners (GPs) receive discharge letters with a delay and relevant
      information about DM is lacking. The aim of this study was to assess the point of
      view of German GPs concerning the information about DM, since no recent data
      about this topic is available. METHODS AND PARTICIPANTS: In a postal survey 516
      GPs in the city of Berlin were contacted and asked about the transit of discharge
      letters and the information about DM. Results | 117 GPs answered the
      questionnaire (23 %). Most frequently, the patient himself handed over the
      information about DM to the GP on the day of his first visit in the practice
      after discharge. However, more than two third of GPs wished to receive the
      information before the patient's first consultation (73 %). Therefore, the
      majority preferred the electronic communication via fax (46 %) or email (9 %).
      Almost half of the GPs stated that discharge letters were lacking information
      about changes in medication and reasons for these changes. At the same time,
      nearly all GPs thought that these informational aspects were important.
      DISCUSSION: GPs wish an early and electronic transit of the DM with information
      concerning changes in medication and reasons. If these wishes were considered, a
      continuous and thus safer pharmacotherapy at the interface could be guaranteed.

PMID- 25945917
TI  - Plasmonic and new plasmonic materials: general discussion.

PMID- 25945916
TI  - Computations underlying Drosophila photo-taxis, odor-taxis, and multi-sensory
      integration.
AB  - To better understand how organisms make decisions on the basis of temporally
      varying multi-sensory input, we identified computations made by Drosophila larvae
      responding to visual and optogenetically induced fictive olfactory stimuli. We
      modeled the larva's navigational decision to initiate turns as the output of a
      Linear-Nonlinear-Poisson cascade. We used reverse-correlation to fit parameters
      to this model; the parameterized model predicted larvae's responses to novel
      stimulus patterns. For multi-modal inputs, we found that larvae linearly combine
      olfactory and visual signals upstream of the decision to turn. We verified this
      prediction by measuring larvae's responses to coordinated changes in odor and
      light. We studied other navigational decisions and found that larvae integrated
      odor and light according to the same rule in all cases. These results suggest
      that photo-taxis and odor-taxis are mediated by a shared computational pathway. 

PMID- 25945918
TI  - Skin testing-directed elimination diet--is 100% efficacy conceivable in
      eosinophilic esophagitis?

PMID- 25945919
TI  - A safe and efficient hepatocyte-selective carrier system based on myristoylated
      preS1/21-47 domain of hepatitis B virus.
AB  - A safe and efficient liver targeted PEGylated liposome (PEG-Lip) based on N
      terminal myristoylated preS1/21-47 (preS1/21-47(myr)) of hepatitis B virus was
      successfully developed. The study aimed to elucidate the cellular uptake
      mechanism of preS1/21-47(myr) modified PEG-Lip (preS1/21-47(myr)-PEG-Lip) in
      hepatogenic cells and the distribution behavior of preS1/21-47(myr)-PEG-Lip in
      Vr:CD1 (ICR) mice. The cellular uptake results showed that preS1/21-47(myr)-PEG
      Lip was effectively taken up by hepatogenic cells (including primary hepatocytes
      and liver tumor cells) through a receptor-mediated endocytosis pathway compared
      with non-hepatogenic cells. After systemic administration to H22 hepatoma-bearing
      mice, preS1/21-47(myr)-PEG-Lip showed significant liver-specific delivery and an
      increase in the distribution of preS1/21-47(myr)-PEG-Lip in hepatic tumor.
      Furthermore, the antitumor effect of preS1/21-47(myr)-PEG-Lip loaded with
      paclitaxel (PTX) was remarkably stronger than that of PTX injection and PTX
      loaded liposomes (including common liposomes and PEG-Lip). In safety evaluation,
      no acute systemic toxicity and immunotoxicity were observed after intravenous
      injection of preS1/21-47(myr)-PEG-Lip. No liver toxicity was observed despite the
      dramatic increase of preS1/21-47(myr)-PEG-Lip in liver. Taken together, preS1/21
      47(myr)-PEG-Lip represents a promising carrier system for targeted liver disease
      therapy and imaging. 

PMID- 25945920
TI  - 4-Hydroxy-2-nonenal (4-HNE) and Its Lipation Product 2-Pentylpyrrole Lysine (2
      PPL) in Peanuts.
AB  - After synthesis of a deuterated 4-hydroxy-2-nonenal (4-HNE) standard, the
      formation of 4-HNE during heating of peanut oil and whole peanuts, respectively,
      was measured by GC-MS. Whereas a significant increase in 4-HNE levels was
      observed for peanut oil, the amount of 4-HNE decreased when whole peanuts were
      roasted due to lipation reactions with amino acid side chains of the proteins.
      The epsilon-amino group of lysine was identified as the favored reaction partner
      of 4-HNE. After heating N(alpha)-acetyl-l-lysine and 4-HNE, a Schiff base, a
      novel pyridinium derivative, a 2-pentylpyrrol derivative and, following reduction
      and hydrolysis, a reduced, cyclized Michael adduct were identified. 2-Amino-6-(2
      pentyl-1H-pyrrol-1-yl)hexanoic acid (2-PPL) was synthesized and quantitated in
      peanut proteins, which had been incubated with various amounts of 4-HNE by HPLC
      ESI-MS/MS after enzymatic hydrolysis. At low 4-HNE concentrations the
      modification of lysine could be entirely explained by the formation of 2-PPL.
      Additionally, 2-PPL was quantified for the first time in peanut samples, and an
      increase depending on the roasting time was observed. 2-PPL represents a suitable
      marker to evaluate the extent of food protein lipation by 4-HNE. 

PMID- 25945921
TI  - Editorial: showing due DILI-gence--the lessons from anabolic steroids.

PMID- 25945922
TI  - Barriers to the use of paediatric clinical practice guidelines in rural and
      regional New South Wales Australia.
AB  - OBJECTIVE: To identify barriers to compliance with paediatric clinical practice
      guidelines (CPGs) in emergency departments in rural and regional New South Wales
      (NSW), Australia, and to propose strategies to increase their use. DESIGN: Cross
      sectional survey. SETTING: Ten emergency departments in rural and regional NSW.
      PARTICIPANTS: Fifty medical officers. MAIN OUTCOME MEASURES: Use of clinical
      practice guidelines and perceived barriers to their usage. RESULTS: Only 22% of
      medical officers reported that they used the CPGs frequently when managing sick
      children. Major barriers to the use of CPGs were a lack of awareness of their
      existence, a lack of training in their use and poor access to the guidelines in
      printed or electronic format. CONCLUSION: In order to increase compliance with
      the paediatric CPGs, medical officers in rural and regional NSW require further
      training and education. The CPGs need to be readily available in either printed
      or electronic format.

PMID- 25945923
TI  - Retinol binding protein 4 plasma level in myelodysplastic syndrome subgroups.

PMID- 25945924
TI  - The Impact of Different Levels of Adaptive Iterative Dose Reduction 3D on Image
      Quality of 320-Row Coronary CT Angiography: A Clinical Trial.
AB  - PURPOSE: The aim of this study was the systematic image quality evaluation of
      coronary CT angiography (CTA), reconstructed with the 3 different levels of
      adaptive iterative dose reduction (AIDR 3D) and compared to filtered back
      projection (FBP) with quantum denoising software (QDS). METHODS: Standard-dose
      CTA raw data of 30 patients with mean radiation dose of 3.2 +/- 2.6 mSv were
      reconstructed using AIDR 3D mild, standard, strong and compared to FBP/QDS.
      Objective image quality comparison (signal, noise, signal-to-noise ratio (SNR),
      contrast-to-noise ratio (CNR), contour sharpness) was performed using 21
      measurement points per patient, including measurements in each coronary artery
      from proximal to distal. RESULTS: Objective image quality parameters improved
      with increasing levels of AIDR 3D. Noise was lowest in AIDR 3D strong (p <= 0.001
      at 20/21 measurement points; compared with FBP/QDS). Signal and contour sharpness
      analysis showed no significant difference between the reconstruction algorithms
      for most measurement points. Best coronary SNR and CNR were achieved with AIDR 3D
      strong. No loss of SNR or CNR in distal segments was seen with AIDR 3D as
      compared to FBP. CONCLUSIONS: On standard-dose coronary CTA images, AIDR 3D
      strong showed higher objective image quality than FBP/QDS without reducing
      contour sharpness. TRIAL REGISTRATION: Clinicaltrials.gov NCT00967876.

PMID- 25945925
TI  - Organization of the Human Frontal Pole Revealed by Large-Scale DTI-Based
      Connectivity: Implications for Control of Behavior.
AB  - The goal of the current study was to examine the pattern of anatomical
      connectivity of the human frontal pole so as to inform theories of function of
      the frontal pole, perhaps one of the least understood region of the human brain.
      Rather than simply parcellating the frontal pole into subregions, we focused on
      examining the brain regions to which the frontal pole is anatomically and
      functionally connected. While the current findings provided support for previous
      work suggesting the frontal pole is connected to higher-order sensory association
      cortex, we found novel evidence suggesting that the frontal pole in humans is
      connected to posterior visual cortex. Furthermore, we propose a functional
      framework that incorporates these anatomical connections with existing cognitive
      theories of the functional organization of the frontal pole. In addition to a
      previously discussed medial-lateral distinction, we propose a dorsal-ventral
      gradient based on the information the frontal pole uses to guide behavior. We
      propose that dorsal regions are connected to other prefrontal regions that
      process goals and action plans, medial regions are connected to other brain
      regions that monitor action outcomes and motivate behaviors, and ventral regions
      connect to regions that process information about stimuli, values, and emotion.
      By incorporating information across these different levels of information, the
      frontal pole can effectively guide goal-directed behavior. 

PMID- 25945926
TI  - Attentional control and the self: The Self-Attention Network (SAN).
AB  - Although there is strong evidence that human decision-making is frequently self
      biased, it remains unclear whether self-biases mediate attention. Here we review
      evidence on the relations between self-bias effects in decision-making and
      attention. We ask: Does self-related information capture attention? Do self
      biases modulate pre-attentive processes or do they depend on attentional
      resources being available? We review work on (1) own-name effects, (2) own-face
      effects, and (3) self-biases in associative matching. We argue that self-related
      information does have a differential impact on the allocation of attention and
      that it can alter the saliency of a stimulus in a manner that mimics the effects
      of perceptual-saliency. However, there is also evidence that self-biases depend
      on the availability of attentional resources and attentional expectancies for
      upcoming stimuli. We propose a new processing framework, the Self-Attention
      Network (SAN), in which neural circuits responding to self-related stimuli
      interact with circuits supporting attentional control, to determine our emergent
      behavior. We also discuss how these-bias effects may extend beyond the self to be
      modulated by the broader social context-for example, by cultural experience, by
      an in-group as opposed to an out-group stimulus, and by whether we are engaged in
      joint actions. Self-biases on attention are modulated by social context.

PMID- 25945927
TI  - Preterm or not--an evaluation of estimates of gestational age in a cohort of
      women from Rural Papua New Guinea.
AB  - BACKGROUND: Knowledge of accurate gestational age is required for comprehensive
      pregnancy care and is an essential component of research evaluating causes of
      preterm birth. In industrialised countries gestational age is determined with the
      help of fetal biometry in early pregnancy. Lack of ultrasound and late
      presentation to antenatal clinic limits this practice in low-resource settings.
      Instead, clinical estimators of gestational age are used, but their accuracy
      remains a matter of debate. METHODS: In a cohort of 688 singleton pregnancies
      from rural Papua New Guinea, delivery gestational age was calculated from Ballard
      score, last menstrual period, symphysis-pubis fundal height at first visit and
      quickening as well as mid- and late pregnancy fetal biometry. Published models
      using sequential fundal height measurements and corrected last menstrual period
      to estimate gestational age were also tested. Novel linear models that combined
      clinical measurements for gestational age estimation were developed. Predictions
      were compared with the reference early pregnancy ultrasound (<25 gestational
      weeks) using correlation, regression and Bland-Altman analyses and ranked for
      their capability to predict preterm birth using the harmonic mean of recall and
      precision (F-measure). RESULTS: Average bias between reference ultrasound and
      clinical methods ranged from 0-11 days (95% confidence levels: 14-42 days).
      Preterm birth was best predicted by mid-pregnancy ultrasound (F-measure: 0.72),
      and neuromuscular Ballard score provided the least reliable preterm birth
      prediction (F-measure: 0.17). The best clinical methods to predict gestational
      age and preterm birth were last menstrual period and fundal height (F-measures
      0.35). A linear model combining both measures improved prediction of preterm
      birth (F-measure: 0.58). CONCLUSIONS: Estimation of gestational age without
      ultrasound is prone to significant error. In the absence of ultrasound
      facilities, last menstrual period and fundal height are among the more reliable
      clinical measures. This study underlines the importance of strengthening
      ultrasound facilities and developing novel ways to estimate gestational age.

PMID- 25945929
TI  - Correction: Cell Atavistic Transition: Paired Box 2 Re-Expression Occurs in
      Mature Tubular Epithelial Cells during Acute Kidney Injury and Is Regulated by
      Angiotensin II.

PMID- 25945930
TI  - Correction: A method for multiplex gene synthesis employing error correction
      based on expression.

PMID- 25945928
TI  - Drebrin regulates neuroblast migration in the postnatal mammalian brain.
AB  - After birth, stem cells in the subventricular zone (SVZ) generate neuroblasts
      that migrate along the rostral migratory stream (RMS) to become interneurons in
      the olfactory bulb (OB). This migration is crucial for the proper integration of
      newborn neurons in a pre-existing synaptic network and is believed to play a key
      role in infant human brain development. Many regulators of neuroblast migration
      have been identified; however, still very little is known about the intracellular
      molecular mechanisms controlling this process. Here, we have investigated the
      function of drebrin, an actin-binding protein highly expressed in the RMS of the
      postnatal mammalian brain. Neuroblast migration was monitored both in culture and
      in brain slices obtained from electroporated mice by time-lapse spinning disk
      confocal microscopy. Depletion of drebrin using distinct RNAi approaches in early
      postnatal mice affects neuroblast morphology and impairs neuroblast migration and
      orientation in vitro and in vivo. Overexpression of drebrin also impairs
      migration along the RMS and affects the distribution of neuroblasts at their
      final destination, the OB. Drebrin phosphorylation on Ser142 by Cyclin-dependent
      kinase 5 (Cdk5) has been recently shown to regulate F-actin-microtubule coupling
      in neuronal growth cones. We also investigated the functional significance of
      this phosphorylation in RMS neuroblasts using in vivo postnatal electroporation
      of phosphomimetic (S142D) or non-phosphorylatable (S142A) drebrin in the SVZ of
      mouse pups. Preventing or mimicking phosphorylation of S142 in vivo caused
      similar effects on neuroblast dynamics, leading to aberrant neuroblast branching.
      We conclude that drebrin is necessary for efficient migration of SVZ-derived
      neuroblasts and propose that regulated phosphorylation of drebrin on S142
      maintains leading process stability for polarized migration along the RMS, thus
      ensuring proper neurogenesis. 

PMID- 25945931
TI  - The requirement of extracorporeal circulation system for transluminal aortic
      valve replacement: Do we really need it in the catheterization laboratory?
AB  - Transcatheter aortic valve replacement (TAVR) is the mainstay for treating high
      risk patients with aortic stenosis. As the TAVR procedures worldwide keep
      increasing, it is inevitable that more issues and complications will arise. Such
      a complication that merits attention is the conversion of TAVR into open-heart
      surgery and the necessity this complication creates to have an extracorporeal
      circulation system in the catheterization laboratory. This review contains an
      analysis of all major randomized trials and registries on the number and cause of
      TAVR procedures that ended up in open-heart surgery and presents data to
      challenge the prerequisite of extracorporeal circulation system in the cath
      laboratory. (c) 2015 Wiley Periodicals, Inc.

PMID- 25945932
TI  - The Regulation of Lipid Deposition by Insulin in Goose Liver Cells Is Mediated by
      the PI3K-AKT-mTOR Signaling Pathway.
AB  - BACKGROUND: We previously showed that the fatty liver formations observed in
      overfed geese are accompanied by the activation of the PI3K-Akt-mTOR pathway and
      an increase in plasma insulin concentrations. Recent studies have suggested a
      crucial role for the PI3K-Akt-mTOR pathway in regulating lipid metabolism;
      therefore, we hypothesized that insulin affects goose hepatocellular lipid
      metabolism through the PI3K-Akt-mTOR signaling pathway. METHODS: Goose primary
      hepatocytes were isolated and treated with serum-free media supplemented with
      PI3K-Akt-mTOR pathway inhibitors (LY294002, rapamycin, and NVP-BEZ235,
      respectively) and 50 or 150 nmol/L insulin. RESULTS: Insulin induced strong
      effects on lipid accumulation as well as the mRNA and protein levels of genes
      involved in lipogenesis, fatty acid oxidation, and VLDL-TG assembly and secretion
      in primary goose hepatocytes. The stimulatory effect of insulin on lipogenesis
      was significantly decreased by treatment with PI3K-Akt-mTOR inhibitors. These
      inhibitors also rescued the insulin-induced down-regulation of fatty acid
      oxidation and VLDL-TG assembly and secretion. CONCLUSION: These findings suggest
      that the stimulatory effect of insulin on lipid deposition is mediated by PI3K
      Akt-mTOR regulation of lipogenesis, fatty acid oxidation, and VLDL-TG assembly
      and secretion in goose hepatocytes.

PMID- 25945933
TI  - Microcystin mcyA and mcyE Gene Abundances Are Not Appropriate Indicators of
      Microcystin Concentrations in Lakes.
AB  - Cyanobacterial harmful algal blooms (cyanoHABs) are a primary source of water
      quality degradation in eutrophic lakes. The occurrence of cyanoHABs is ubiquitous
      and expected to increase with current climate and land use change scenarios.
      However, it is currently unknown what environmental parameters are important for
      indicating the presence of cyanoHAB toxins making them difficult to predict or
      even monitor on time-scales relevant to protecting public health. Using qPCR, we
      aimed to quantify genes within the microcystin operon (mcy) to determine which
      cyanobacterial taxa, and what percentage of the total cyanobacterial community,
      were responsible for microcystin production in four eutrophic lakes. We targeted
      Microcystis-16S, mcyA, and Microcystis, Planktothrix, and Anabaena-specific mcyE
      genes. We also measured microcystins and several biological, chemical, and
      physical parameters--such as temperature, lake stability, nutrients, pigments and
      cyanobacterial community composition (CCC)--to search for possible correlations
      to gene copy abundance and MC production. All four lakes contained Microcystis
      mcyE genes and high percentages of toxic Microcystis, suggesting Microcystis was
      the dominant microcystin producer. However, all genes were highly variable
      temporally, and in few cases, correlated with increased temperature and nutrients
      as the summer progressed. Interestingly, toxin gene abundances (and biomass
      indicators) were anti-correlated with microcystin in all lakes except the largest
      lake, Lake Mendota. Similarly, gene abundance and microcystins differentially
      correlated to CCC in all lakes. Thus, we conclude that the presence of
      microcystin genes are not a useful tool for eliciting an ecological role for
      toxins in the environment, nor are microcystin genes (e.g. DNA) a good indicator
      of toxins in the environment.

PMID- 25945935
TI  - Ultrasound-guided pulsed radio frequency treatment in Morton's neuroma.
AB  - BACKGROUND: Morton's neuroma is a perineural fibrosis of an intermetatarsal
      plantar nerve. Burning, numbness, paresthesia, and tingling down the interspaces
      of involved toes may also be experienced. Taking into account all of this
      information, we designed a prospective open-label study to evaluate the efficacy
      of pulsed radio frequency on Morton's neuroma. METHODS: Twenty patients with
      Morton's neuroma were experiencing symptomatic neuroma pain in the foot not
      relieved by routine conservative treatment. All of the patients had been
      evaluated by a specialized orthopedist and were offered pulsed radio frequency as
      a last option before having surgery. Initially, pain level (numerical rating
      scale), successful pain control (a >=50% pain decrease was accepted as successful
      pain control), comfort when walking (yes or no), and satisfaction level
      (satisfied or not satisfied) were evaluated. RESULTS: We found a decrease in the
      pain level in 18 of 20 patients, successful pain control in 12, and wearing shoes
      and walking without pain in 16. Overall, satisfaction was rated as excellent or
      good by 12 patients with Morton's neuroma in this series. CONCLUSIONS: This
      evidence indicates that ultrasound-guided pulsed radio frequency is a promising
      treatment modality in the management of Morton's neuroma pain.

PMID- 25945934
TI  - Mitochondrial GWA Analysis of Lipid Profile Identifies Genetic Variants to Be
      Associated with HDL Cholesterol and Triglyceride Levels.
AB  - It has been suggested that mitochondrial dysfunction has an influence on lipid
      metabolism. The fact that mitochondrial defects can be accumulated over time as a
      normal part of aging may explain why cholesterol levels often are altered with
      age. To test the hypothesis whether mitochondrial variants are associated with
      lipid profile (total cholesterol, LDL, HDL, and triglycerides) we analyzed a
      total number of 978 mitochondrial single nucleotide polymorphisms (mtSNPs) in a
      sample of 2,815 individuals participating in the population-based KORA F4 study.
      To assess mtSNP association while taking the presence of heteroplasmy into
      account we used the raw signal intensity values measured on the microarray and
      applied linear regression. Ten mtSNPs (mt3285, mt3336, mt5285, mt6591, mt6671,
      mt9163, mt13855, mt13958, mt14000, and mt14580) were significantly associated
      with HDL cholesterol and one mtSNP (mt15074) with triglycerides levels. These
      results highlight the importance of the mitochondrial genome among the factors
      that contribute to the regulation of lipid levels. Focusing on mitochondrial
      variants may lead to further insights regarding the underlying physiological
      mechanisms, or even to the development of innovative treatments. Since this is
      the first mitochondrial genome-wide association analysis (mtGWAS) for lipid
      profile, further analyses are needed to follow up on the present findings. 

PMID- 25945936
TI  - The changing effect of economic development on the consumption-based carbon
      intensity of well-being, 1990-2008.
AB  - Recent sustainability science research focuses on tradeoffs between human well
      being and stress placed on the environment from fossil fuel consumption, a
      relationship known as the carbon intensity of well-being (CIWB). In this study we
      assess how the effect of economic development on consumption-based CIWB--a ratio
      of consumption-based carbon dioxide emissions to average life expectancy--changed
      from 1990 to 2008 for 69 nations throughout the world. We examine the effect of
      development on consumption-based CIWB for the overall sample as well as for
      smaller samples restricted to mostly high-income OECD nations, Non-OECD nations,
      and more nuanced regional samples of Non-OECD nations in Africa, Asia, and Latin
      America. We find that the effect of economic development on CIWB increased
      through time for the overall sample. However, analyses of the Non-OECD and OECD
      samples indicate that while the effect of development on CIWB increased from null
      to a moderate level for the Non-OECD nations, the effect of economic development
      was much larger, relatively stable through time, and more unsustainable for the
      OECD nations. Additional findings reveal important regional differences for Non
      OECD nations. In the early 1990s, increased development led to a reduction in
      CIWB for Non-OECD nations in Africa, but in more recent years the relationship
      changed, becoming less sustainable. For the samples of Non-OECD nations in Asia
      and Latin America, we find that economic development increased consumption-based
      CIWB, and increasingly so throughout the 19 year period of study.

PMID- 25945938
TI  - Clinical analysis of 152 cases of multiple primary malignant tumors in 15,398
      patients with malignant tumors.
AB  - OBJECTIVES: In this study, the etiology, clinical characteristics, and prognosis
      of multiple primary malignant tumors (MPMTs) were investigated. Furthermore, we
      analyzed the treatment factors associated with MPMTs. METHODS: From 15,398
      patients with malignant tumors presenting to The First Hospital of Jilin
      University, China, between January 2010 and December 2013, we identified and
      analyzed patients with MPMTs. Data were obtained retrospectively from the
      hospital database. RESULTS: The prevalence of MPMTs in this study was 0.99%
      (152/15398): 51 cases were synchronous MPMTs, and 101 cases were metachronous
      MPMTs. The mean time between the first and second primary cancer was 43.1 months.
      In this population, MPMTs were observed more frequently in patients with head and
      neck tumors (5.65%) and urinary tumors (4.19%); the prevalence of MPMTs in these
      patients was over 4-fold greater than the prevalence of MPMTs in all patients
      (0.99%). There were no cases of MPMTs in 132 cases of nervous system tumors and
      404 cases of multiple myeloma. Nearly 50% (45.4%) of patients with MPMTs did not
      receive chemotherapy or radiotherapy before the second primary cancer was
      diagnosed. Eighty-five patients with MPMTs were followed for more than 2 years,
      and the 2-year cumulative survival rate was 40.8%. CONCLUSIONS: In this study,
      the prevalence of MPMTs was 0.99% (152/15398), which is consistent with the
      Chinese literature. Patients with head and neck tumors or urinary tumors are at
      greater risk of developing MPMTs. In addition to radiotherapy or chemotherapy,
      this study suggests that other factors may contribute to MPMTs.

PMID- 25945937
TI  - Development of a cell-based bioassay for phospholipase A2-triggered liposomal
      drug release.
AB  - The feasibility of exploiting secretory phospholipase A2 (sPLA2) enzymes, which
      are overexpressed in tumors, to activate drug release from liposomes precisely at
      the tumor site has been demonstrated before. Although the efficacy of the
      developed formulations was evaluated using in vitro and in vivo models, the
      pattern of sPLA2-assisted drug release is unknown due to the lack of a suitable
      bio-relevant model. We report here on the development of a novel bioluminescence
      living-cell-based luciferase assay for the monitoring of sPLA2-triggered release
      of luciferin from liposomes. To this end, we engineered breast cancer cells to
      produce both luciferase and sPLA2 enzymes, where the latter is secreted to the
      extracellular medium. We report on setting up a robust and reproducible bioassay
      for testing sPLA2-sensitive, luciferin remote-loaded liposomal formulations,
      using 1,2-distearoyl-sn-glycero-3-phosphatidylcholine/1,2-distearoyl-sn-glycero-3
      phosphatidylglycerol (DSPC/DSPG) 7:3 and DSPC/DSPG/cholesterol 4:3:3 as initial
      test systems. Upon their addition to the cells, the liposomes were degraded
      almost instantaneously by sPLA2 releasing the encapsulated luciferin, which
      provided readout from the luciferase-expressing cells. Cholesterol enhanced the
      integrity of the formulation without affecting its susceptibility to sPLA2.
      PEGylation of the liposomes only moderately broadened the release profile of
      luciferin. The provided bioassay represents a useful tool for monitoring active
      drug release in situ in real time as well as for testing and optimizing of sPLA2
      sensitive lipid formulations. In addition, the bioassay will pave the way for
      future in-depth in vitro and in vivo studies.

PMID- 25945939
TI  - Genetic Variation, Structure, and Gene Flow in a Sloth Bear (Melursus ursinus)
      Meta-Population in the Satpura-Maikal Landscape of Central India.
AB  - Sloth bears (Melursus ursinus) are endemic to the Indian subcontinent. As a
      result of continued habitat loss and degradation over the past century, sloth
      bear populations have been in steady decline and now exist only in isolated or
      fragmented habitat across the entire range. We investigated the genetic
      connectivity of the sloth bear meta-population in five tiger reserves in the
      Satpura-Maikal landscape of central India. We used noninvasively collected fecal
      and hair samples to obtain genotypic information using a panel of seven
      polymorphic loci. Out of 194 field collected samples, we identified 55
      individuals in this meta-population. We found that this meta-population has
      moderate genetic variation, and is subdivided into two genetic clusters. Further,
      we identified five first-generation migrants and signatures of contemporary gene
      flow. We found evidence of sloth bears in the corridor between the Kanha and
      Pench Tiger Reserves, and our results suggest that habitat connectivity and
      corridors play an important role in maintaining gene flow in this meta
      population. These corridors face several anthropogenic and infrastructure
      development threats that have the potential to sever ongoing gene flow, if
      policies to protect them are not put into action immediately. 

PMID- 25945941
TI  - Polymorphisms of inflammatory markers and risk of essential hypertension in
      Tatars from Russia.
AB  - Essential hypertension (EH) is a common disease with a clear genetic component.
      Inflammation and endothelial dysfunction play a prominent role in the development
      of persistent blood pressure elevation. The aim of the current study was to
      detect an association between EH and polymorphic markers in genes encoding for
      molecules involved in the control of intercellular interactions during the
      inflammation process. We analysed SNPs in SELE, SELP, SELL, ICAM1, VEGFA, IL1B,
      IL6, IL10 and IL12B genes in a group of 534 men of Tatar ethnicity (217 patients
      with EH and 317 controls). Using a Markov chain Monte-Carlo-based approach
      (APSampler), we found genotype and allelic combinations associated with EH. The
      most significant associations were observed for SELE rs2076059*C-SELP rs6131*A
      VEGFA -2549*I-IL1B rs16944*C (p = 3.42 * 10(-5), FDR q = 0.035) and SELE
      rs2076059*C-SELP rs6131*A-IL12B rs3212227*C-IL1B rs16944*C (p = 323 * 10(-4), FDR
      q = 0.035). 

PMID- 25945943
TI  - A free radical cascade silylarylation of activated alkenes: highly selective
      activation of the Si-H/C-H bonds.
AB  - The first example of silylarylation of activated alkenes with silanes is reported
      via selective activation of the Si-H/C-H bonds, which allows efficient access to
      silylated oxindoles through a free-radical cascade process. 

PMID- 25945942
TI  - General psychiatric symptoms, quality of sleep, and coping strategies in patients
      with psoriasis vulgaris.
AB  - BACKGROUND: Psoriasis is a common dermatological disorder with psychiatric
      comorbidity. Psoriasis is associated with a variety of psychological problems,
      including poor self-esteem, sexual dysfunction, sleep disturbances, anxiety,
      depression, and suicidal ideation. OBJECTIVES: We aimed to investigate general
      psychiatric symptoms, quality of sleep, and coping strategies in patients with
      psoriasis vulgaris. METHODS: A total of 79 subjects (37 patients with psoriasis
      vulgaris and 42 control subjects) were enrolled in the study. Coping strategies
      were measured using the Coping Orientations to Problems Experienced (COPE) Scale.
      General psychopathological status was assessed using the Symptom Checklist-90-R
      (SCL90R), and sleep quality and disturbances were assessed using the Pittsburgh
      Sleep Quality Index (PSQI). RESULTS: The mean age of the patients was 39.18 +/-
      16.85 years. The mean age of control subjects was 39.33 +/- 11.61 years. The mean
      score on the Psoriasis Area and Severity Index (PASI) was 7.56 +/- 3.66. There
      were no significant differences in scores on the SCL90R and COPE subscales
      between the patient and control groups. However, significant differences between
      the groups emerged on the PSQI subscales for subjective sleep quality and
      habitual sleep efficiency (Z = -1.964, P = 0.049, and Z = -2.452, P = 0.014,
      respectively). CONCLUSIONS: The present study found no significant differences in
      general psychiatric symptoms and coping strategies between the psoriasis patients
      and the control group, by contrast with findings reported elsewhere in the
      literature. We think that the low PASI scores of our patients, which indicate the
      low severity of disease in the present group, is the main reason for this
      finding. However, sleep quality is lower in psoriasis vulgaris patients than in
      healthy controls. This may be associated with the itch and pain caused by
      lesions. Further experimental studies are required to explain these findings.

PMID- 25945944
TI  - 'What I learnt from you' - Supportive written feedback for GP trainees after
      clinical teaching visits.

PMID- 25945945
TI  - A BEME systematic review of UK undergraduate medical education in the general
      practice setting: BEME Guide No. 32.
AB  - BACKGROUND: General practice is increasingly used as a learning environment in
      undergraduate medical education in the UK. AIM: The aim of this project was to
      identify, summarise and synthesise research about undergraduate medical education
      in general practice in the UK. METHODS: We systematically identified studies of
      undergraduate medical education within a general practice setting in the UK from
      1990 onwards. All papers were summarised in a descriptive report and categorised
      into two in-depth syntheses: a quantitative and a qualitative in-depth review.
      RESULTS: 169 papers were identified, representing research from 26 UK medical
      schools. The in-depth review of quantitative papers (n = 7) showed that medical
      students learned clinical skills as well or better in general practice settings.
      Students receive more teaching, and clerk and examine more patients in the
      general practice setting than in hospital. Patient satisfaction and enablement
      are similar whether a student is present or not in a consultation, however,
      patients experience lower relational empathy. Two main thematic groups emerged
      from the qualitative in-depth review (n = 10): the interpersonal interactions
      within the teaching consultation and the socio-cultural spaces of learning which
      shape these interactions. The GP has a role as a broker of the interactions
      between patients and students. General practice is a socio-cultural and
      developmental learning space for students, who need to negotiate the competing
      cultures between hospital and general practice. Lastly, patients are transient
      members of the learning community, and their role requires careful facilitation.
      CONCLUSIONS: General practice is as good, if not better, than hospital delivery
      of teaching of clinical skills. Our meta-ethnography has produced rich
      understandings of the complex relationships shaping possibilities for student and
      patient active participation in learning.

PMID- 25945947
TI  - Effect of comorbid diabetes and hypercholesterolemia on the prognosis of
      idiopathic sudden sensorineural hearing loss.
AB  - OBJECTIVES: We tested the hypothesis that comorbid diseases significantly affect
      the prognosis of sudden sensorineural hearing loss (ISSNHL). STUDY DESIGN: A
      retrospective cohort study. METHODS: The records of patients newly diagnosed with
      ISSNHL and treated with steroid prednisolone in a tertiary referral center
      between January 2003 and December 2013 were retrospectively reviewed.
      Pretreatment and posttreatment hearing levels were evaluated using pure-tone
      average (PTA) and word recognition score (WRS). The comorbidities of diabetes,
      hypertension, coronary artery disease, hypercholesterolemia, cerebrovascular
      disease, chronic kidney disease, and anemia were identified. We examined the
      effects of these comorbid diseases on the prognosis of ISSNHL 2 months
      posttreatment. RESULTS: Regression analyses adjusted for gender, age,
      pretreatment hearing, treatment delay time, and all the comorbidities showed that
      the probability of major improvement in the PTA was significantly higher in
      patients without diabetes compared to those with diabetes (univariate odds ratio
      [OR], 1.90; 95% confidence interval (CI), 1.25-2.90; multivariate OR, 1.69; 95%
      CI, 1.03-2.77). Major (>= 90%) and moderate (50%-89% improvement of the PTA, but
      with a remaining hearing loss of > 10 dB) improvement in the PTA was
      significantly higher in patients without hypercholesterolemia compared to those
      with hypercholesterolemia (univariate OR, 1.78; 95% CI, 1.13-2.80; multivariate
      OR, 1.70; 95% CI, 1.02-2.84). There was, however, no significant difference in
      the distribution of major (>= 90%), moderate (50%-89%), and minor (< 50%)
      improvement in the posttreatment WRS for these comorbid diseases. CONCLUSIONS:
      Comorbid diabetes or hypercholesterolemia may indicate a smaller probability of
      major or moderate PTA improvement for patients with ISSNHL.

PMID- 25945946
TI  - AN OPEN TRIAL OF EMOTION REGULATION THERAPY FOR GENERALIZED ANXIETY DISORDER AND
      COOCCURRING DEPRESSION.
AB  - BACKGROUND: Although CBT is efficacious for a wide variety of psychiatric
      conditions, relatively fewer GAD patients achieve high endstate functioning as
      compared to patients receiving CBTs for other disorders. Moreover, GAD trials
      that utilized patient samples without prominent depression have tended to report
      that effect sizes for depressive outcomes were small or diminished to
      pretreatment levels in the follow-up period. Emotion regulation therapy (ERT)
      integrates principles from traditional and contemporary cognitive behavioral
      treatments with basic and translational findings from affect science to offer a
      blueprint for improving intervention by focusing on motivational, regulatory, and
      contextual learning mechanisms. METHOD: The purpose of this investigation was to
      provide initial support for the efficacy of ERT in an open trial of patients with
      GAD and cooccurring depressive symptoms. Twenty-one patients received a 20
      session version of ERT delivered in weekly individual sessions. Standardized
      clinician ratings and self-report measures were assessed at pre-, mid-, and
      posttreatment as well as at three- and nine-month follow-ups. Intent-to-treat
      analyzes were utilized. RESULTS: GAD patients, half with comorbid major
      depression, evidenced statistically, and clinically meaningful improvements in
      symptom severity, impairment, quality of life, and in model-related outcomes
      including emotional/motivational intensity, mindful attending/acceptance,
      decentering, and cognitive reappraisal. Patients maintained gains across the
      three and nine month follow-up periods. CONCLUSIONS: These findings, although
      preliminary, provide additional evidence for the role of emotion dysregulation in
      the onset, maintenance, and now treatment of conditions such as GAD and
      cooccurring depressive symptoms.

PMID- 25945948
TI  - DMSO-Li2O2 Interface in the Rechargeable Li-O2 Battery Cathode: Theoretical and
      Experimental Perspectives on Stability.
AB  - One of the greatest obstacles for the realization of the nonaqueous Li-O2 battery
      is finding a solvent that is chemically and electrochemically stable under cell
      operating conditions. Dimethyl sulfoxide (DMSO) is an attractive candidate for
      rechargeable Li-O2 battery studies; however, there is still significant
      controversy regarding its stability on the Li-O2 cathode surface. We performed
      multiple experiments (in situ XPS, FTIR, Raman, and XRD) which assess the
      stability of the DMSO-Li2O2 interface and report perspectives on previously
      published studies. Our electrochemical experiments show long-term stable cycling
      of a DMSO-based operating Li-O2 cell with a platinum@carbon nanotube core-shell
      cathode fabricated via atomic layer deposition, specifically with >45 cycles of
      40 h of discharge per cycle. This work is complemented by density functional
      theory calculations of DMSO degradation pathways on Li2O2. Both experimental and
      theoretical evidence strongly suggests that DMSO is chemically and
      electrochemically stable on the surface of Li2O2 under the reported operating
      conditions. 

PMID- 25945949
TI  - An intramolecular G-quadruplex structure formed in the human MET promoter region
      and its biological relevance.
AB  - Previous studies have shown that promoter regions of many proto-oncogenes can
      fold into G-quadruplexes, which are potentially involved in the regulation of
      genes. Bioinformatics analysis suggested that there was a G-rich sequence within 
      48 to -26 region of the human MET promoter (named Pu23WT). In this study, we
      proved that Pu23WT adopted an intramolecular parallel G-quadruplex structure
      under physiological conditions in vitro, and the cationic porphyrin TMPyP4
      enhanced the stability of the Pu23WT G-quadruplex. To better understand the
      functions of Pu23WT in the MET expression, we performed a series of analysis on
      several cancer cells. Experimental data revealed that TMPyP4 treatment attenuated
      the expression of MET in HepG2, BGC823, and U87MG cells, resulting in the
      cellular proliferation inhibition, G1 phase cell cycle arrest and cell migration
      retardation. ChIP assay results indicated that TMPyP4 probably prohibited the
      Pu23WT G-quadruplex from binding to the activator Sp1, which could be one of the
      mechanisms that led to the transcription inhibition of MET gene. It is the first
      study on the G-quadruplex structure in the human MET promoter and its functions
      in cancer cells. We believe that this structure is a potential target for
      anticancer treatment.

PMID- 25945950
TI  - Rumble: Prevalence and Correlates of Group Fighting among Adolescents in the
      United States.
AB  - OBJECTIVE: Group fighting is portrayed as a piece of Americana among delinquent
      youth, but the behavior produces significant multifaceted negative consequences.
      The current study examines the heterogeneity and correlates of group fighting
      using national-level data. METHOD: Employing data from the National Survey on
      Drug Use and Health between 2002 and 2013 (n = 216,852), we examine links between
      group fighting and temperamental, parental, and academic factors as well as other
      externalizing behaviors (i.e., violence, crime, substance use). RESULTS: The
      prevalence of group fighting in the United States is 14.8% with 11.33% reporting
      1-2 group fights and 3.46% reporting 3+ group fights. A clear severity gradient
      in school functioning and academic performance, sensation seeking, parental
      disengagement, violence and delinquency, and substance use disorders is seen in
      the normative, episodic, and repeat offender groups. CONCLUSIONS: Youths who
      participate in 3+ group fights display the exceptionality and severity of other
      serious/chronic/habitual antisocial youth which suggests that group fighting
      should be considered a significant indicator of developing criminality.

PMID- 25945952
TI  - Hair regrowth through wound healing process after ablative fractional laser
      treatment in a murine model.
AB  - BACKGROUND AND OBJECTIVE: Alopecia is one of the most common dermatological
      problems in the elderly; however, current therapies for it are limited by low
      efficacy and undesirable side effects. Although clinical reports on fractional
      laser treatment for various alopecia types are increasing, the exact mechanism
      remains to be clarified. The purposes of this study were to demonstrate the
      effect of ablative fractional laser treatment on hair follicle regrowth in vivo
      and investigate the molecular mechanism after laser treatment. MATERIALS AND
      METHODS: Ablative CO2 fractional laser was applied to the shaved dorsal skin of 7
      week-old C57BL/6 mice whose hair was in the telogen stage. After 12 mice were
      treated at various energy (10-40 mJ/spot) and density (100-400 spots/cm(2) )
      settings to determine the proper dosage for maximal effect. Six mice were then
      treated at the decided dosage and skin specimens were sequentially obtained by
      excision biopsy from the dorsal aspect of each mouse. Tissue samples were used
      for the immunohistochemistry and reverse transcription polymerase chain reaction
      assays to examine hair follicle status and their related molecules. RESULTS: The
      most effective dosage was the 10 mJ/spot and 300 spots/cm(2) setting. The anagen
      conversion of hair was observed in the histopathological examination, while
      Wnt/beta-catenin expression was associated with hair regrowth in the
      immunohistochemistry and molecular studies. CONCLUSIONS: Ablative fractional
      lasers appear to be effective for inducing hair regrowth via activation of the
      Wnt/beta-catenin pathway in vivo. Our findings indicate that fractional laser
      treatment can potentially be developed as new treatment options for stimulating
      hair regrowth.

PMID- 25945953
TI  - New method to assess mitophagy flux by flow cytometry.
AB  - Mitochondrial autophagy, also known as mitophagy, is an autophagosome-based
      mitochondrial degradation process that eliminates unwanted or damaged
      mitochondria after cell stress. Most studies dealing with mitophagy rely on the
      analysis by fluorescence microscopy of mitochondrial-autophagosome
      colocalization. However, given the fundamental role of mitophagy in the
      physiology and pathology of organisms, there is an urgent need for novel
      quantitative methods with which to study this process. Here, we describe a flow
      cytometry-based approach to determine mitophagy by using MitoTracker Deep Red, a
      widely used mitochondria-selective probe. Used in combination with selective
      inhibitors it may allow for the determination of mitophagy flux. Here, we test
      the validity of the use of this method in cell lines and in primary cell and
      tissue cultures. 

PMID- 25945954
TI  - Methylphenidate mediated change in prosody is specific to the performance of a
      cognitive task in female adult ADHD patients.
AB  - OBJECTIVES: Prosody production is highly personalized, related to both the
      emotional and cognitive state of the speaker and to the task being performed.
      Fundamental frequency (F main) is a central measurable feature of prosody,
      associated with having an attention deficit hyperactive disorder (ADHD). Since
      methylphenidate is an effective therapy for ADHD, we hypothesized that it will
      affect the fundamental frequency of ADHD patients. METHODS: The answers of 32
      adult ADHD patients were recorded while performing two computerized tasks
      (cognitive and emotional). Evaluations were performed at baseline and an hour
      after patients received methylphenidate. RESULTS: A significant effect of
      methylphenidate was observed on the fundamental frequency, as opposed to other
      parameters, of prosody. This change was evident while patients performed a
      cognitive, as opposed to an emotional, task. This change was seen in the 14
      female ADHD patients but not in the 18 male ADHD patients. The fundamental
      frequency while performing a cognitive task without methylphenidate was not
      different in the female ADHD group, from 22 female controls. CONCLUSIONS: This
      pilot study supports prosodic changes as possible objective and accessible
      dynamic biological marker of treatment responses specifically in female ADHD.

PMID- 25945955
TI  - Bond-weakening catalysis: conjugate aminations enabled by the soft homolysis of
      strong N-H bonds.
AB  - The ability of redox-active metal centers to weaken the bonds in associated
      ligands is well precedented, but has rarely been utilized as a mechanism of
      substrate activation in catalysis. Here we describe a catalytic bond-weakening
      protocol for conjugate amination wherein the strong N-H bonds in N-aryl amides (N
      H bond dissociation free energies ~100 kcal/mol) are destabilized by ~33 kcal/mol
      upon by coordination to a reducing titanocene complex, enabling their abstraction
      by the weak H-atom acceptor TEMPO through a proton-coupled electron transfer
      process. Significantly, this soft homolysis mechanism provides a method to
      generate closed-shell, metalated nucleophiles under neutral conditions in the
      absence of a Bronsted base. 

PMID- 25945957
TI  - "Myopia, corneas, refractive errors and vision".

PMID- 25945956
TI  - Drug resistance is rarely the cause or consequence of long-term persistent low
      level viraemia in HIV-1-infected patients on ART.
AB  - BACKGROUND: The introduction of highly sensitive HIV-1 viral load assays with a
      lower quantification limit of 20 copies/ml uncovered that in a number of patients
      on ART, the viral load systematically fluctuates around or slightly above the
      detection limit of the assays. This study aimed to analyse the presence or
      occurrence of drug resistance mutations in HIV-1-infected patients during long
      term persistent low-level viraemia (PLLV) under ART. METHODS: A retrospective
      study was carried out in which baseline and on-therapy presence of drug
      resistance mutations in the HIV-1 protease and reverse transcriptase genes were
      analysed in patients with PLLV between 20 and 250 copies/ml. For all available
      plasma samples collected during PLLV, resistance analysis was attempted with an
      ultrasensitive amplification and sequencing protocol. RESULTS: Resistance
      analysis was successful for 154 samples collected longitudinally from 23 patients
      over a median period of 4.7 years (IQR 3.3-5.7). Twenty of these patients were on
      a boosted protease inhibitor (PI)-based regimen (87%). Single drug resistance
      mutations were detected in isolated samples of 4 patients, 2 of the 3 patients
      who initiated a non-nucleoside reverse transcriptase inhibitor-based regimen and
      2 of the 20 on a PI-based regimen. Only one of the detected mutations decreased
      susceptibility to the therapy regimen taken at the time of sample collection.
      Drug resistance mutations were not found in the three patients who developed
      virological failure (viral load >250 copies/ml) during the study. CONCLUSIONS:
      Long episodes of PLLV in patients on boosted PI-based regimens rarely result in
      the selection of new drug-resistant variants.

PMID- 25945959
TI  - Biometric parameters in different stages of primary angle closure using low
      coherence interferometry.
AB  - PURPOSE: To compare ocular biometric parameters using low-coherence
      interferometry among siblings affected with different degrees of primary angle
      closure (PAC). METHODS: In this cross-sectional comparative study, a total of 170
      eyes of 86 siblings from 47 families underwent low-coherence interferometry
      (LenStar 900; Haag-Streit, Koeniz, Switzerland) to determine central corneal
      thickness, anterior chamber depth (ACD), aqueous depth (AD), lens thickness (LT),
      vitreous depth, and axial length (AL). Regression coefficients were applied to
      show the trend of the measured variables in different stages of angle closure. To
      evaluate the discriminative power of the parameters, receiver operating
      characteristic curves were used. Best cutoff points were selected based on the
      Youden index. Sensitivity, specificity, positive and negative predicative values,
      positive and negative likelihood ratios, and diagnostic accuracy were determined
      for each variable. RESULTS: All biometric parameters changed significantly from
      normal eyes to PAC suspects, PAC, and PAC glaucoma; there was a significant
      stepwise decrease in central corneal thickness, ACD, AD, vitreous depth, and AL,
      and an increase in LT and LT/AL. Anterior chamber depth and AD had the best
      diagnostic power for detecting angle closure; best levels of sensitivity and
      specificity were obtained with cutoff values of 3.11 mm for ACD and 2.57 mm for
      AD. CONCLUSIONS: Biometric parameters measured by low-coherence interferometry
      demonstrated a significant and stepwise change among eyes affected with various
      degrees of angle closure. Although the current classification scheme for angle
      closure is based on anatomical features, it has excellent correlation with
      biometric parameters.

PMID- 25945961
TI  - Letter to the editor: visibility through atmospheric haze and its relation to
      macular pigment.

PMID- 25945962
TI  - Authors' response.

PMID- 25945963
TI  - Letter to the editor: choroidal thickness, age, and refractive error in healthy
      Korean subjects.

PMID- 25945965
TI  - Evaluation of WO2011045166A1, Fkbp52-tau interaction as a novel therapeutical
      target for treating the neurological disorders involving tau dysfunction.
AB  - INTRODUCTION: This invention provides the screening methods of candidate
      compounds, the diagnostic methods and the methods of treatment of human cognitive
      diseases, and also gives out several potential candidate compounds. The invention
      establishes that the FKBP52-Tau interaction provides a new target that may be
      used advantageously for novel therapeutic approaches for neurological disorders
      involving Tau dysfunction, and especially for Alzheimer's disease. AREAS COVERED:
      The invention generally relates to neuroprotection and repair in neurological
      disorders involving Tau dysfunction (including Alzheimer's disease). The
      invention describes a direct interaction between FKBP52 and Tau, the screening
      methods for molecules acting on the FKBP52-Tau interaction, in order to modulate
      the detrimental effect of pathogenic Tau. Finally, it discusses therapeutic,
      diagnostic, prognostic and monitoring assays of neurological disorders involving
      Tau dysfunction. EXPERT OPINION: Several methods or techniques were used to
      determine the validity of screening methods, involving biochemistry, immunology,
      fluorescence analysis and cell experiment. Candidate compounds mentioned in the
      patent include FK506 derivatives, rapamycin derivatives and pipecolyl-alpha-keto
      amid compounds. However, the mechanism, the structural similarity and the
      biological activity were unmentioned, which may partly reduce the practicability
      of the invention. The FKBP52-Tau interaction as a novel target for
      neurodegenerative diseases is promising. FKBP52 is capable of preventing
      polymerization of tubulin and maintaining axonal transport. In AD patients'
      brain, the high level of Tau protein phosphorylation is directly related to the
      decrease of FKBP52. The FKBP52-Tau interaction may provide a new critical path
      for treatment of neurodegenerative diseases, and new molecules will possess
      higher affinity and efficiency.

PMID- 25945966
TI  - Correspondence on: "Therapeutic Prospect of Adipose-Derived Stromal Cells for
      Treatment of Abdominal Aortic Aneurysm".

PMID- 25945967
TI  - Bringing home the health humanities: narrative humility, structural competency,
      and engaged pedagogy.
AB  - As health humanities programs grow and thrive across the country, encouraging
      medical students to read, write, and become more reflective about their
      professional roles, educators must bring a sense of self-reflexivity to the
      discipline itself. In the health humanities, novels, patient histories, and
      pieces of reflective writing are often treated as architectural spaces or "homes"
      that one can enter and examine. Yet, narrative-based learning in health care
      settings does not always allow its participants to feel "at home"; when not
      taught with a critical attention to power and pedagogy, the health humanities can
      be unsettling and even dangerous. Educators can mitigate these risks by
      considering not only what they teach but also how they teach it.In this essay,
      the authors present three pedagogical pillars that educators can use to invite
      learners to engage more fully, develop critical awareness of medical narratives,
      and feel "at home" in the health humanities. These pedagogical pillars are
      narrative humility (an awareness of one's prejudices, expectations, and frames of
      listening), structural competency (attention to sources of power and privilege),
      and engaged pedagogy (the protection of students' security and well-being).
      Incorporating these concepts into pedagogical practices can create safe and
      productive classroom spaces for all, including those most vulnerable and at risk
      of being "unhomed" by conventional hierarchies and oppressive social structures.
      This model then can be translated through a parallel process from classroom to
      clinic, such that empowered, engaged, and cared-for learners become empowering,
      engaging, and caring clinicians. 

PMID- 25945968
TI  - Informed Consent for Electroconvulsive Therapy--Finding Balance.
AB  - Informed consent underpins all medical decisions, including the decision to
      undergo electroconvulsive therapy (ECT). Written informed consent remains the
      standard before the initiation of ECT and requires the inclusion of several
      components to be considered valid. Prospective patients must be aware of risks
      and benefits of ECT as well as risks and benefits of alternate, and potentially
      less effective, interventions. Patients must also possess adequate decision
      making capacity to make an informed choice about treatment. Consent for ECT may
      present unique issues, such as the interplay between potential cognitive adverse
      effects and informed consent. Options to address this concern include thorough
      explanation of this topic before the initiation of ECT, continued reassessment of
      consent during ECT, or some combination of approaches. 

PMID- 25945969
TI  - Repetitive Transcranial Magnetic Stimulation for the Treatment of Major
      Depression in a Patient With an Intracranial Space-Occupying Lesion: A Case
      Report of Safety.
AB  - This is the first case report of the safety of therapeutic repetitive
      transcranial magnetic stimulation (rTMS) in a patient with an intracranial space
      occupying lesion who had recurrent major depression. In this case, the
      intracranial space-occupying lesion was a mixed cystic and solid enhancing pineal
      region mass measuring approximately 16.9 * 12.2 * 15.5 mm. The patient remitted
      from depression with 36 sessions of dorsolateral prefrontal cortex rTMS
      treatments over a 6-week period. During the rTMS treatment course, patient's
      medication list included bupropion that potentially can increase the risk for a
      seizure and topiramate that potentially can reduce the risk for seizure
      associated with the treatment. The patient tolerated the rTMS treatment well,
      reporting only transient headache and discomfort at the site of stimulation after
      the treatment. She tolerated the procedure well and had no incidental seizure
      activity throughout her treatment sessions. 

PMID- 25945970
TI  - Myelography iodinated contrast media. I. Unraveling the atropisomerism properties
      in solution.
AB  - The present work reports a thorough conformational analysis of iodinated contrast
      media: iomeprol, iopamidol (the world's most utilized contrast agent), and
      iopromide. Its main aim is the understanding of the complex structural features
      of these atropisomeric molecules, characterized by the presence of many
      conformers with hindered rotations, and of the role of atropisomerism in the
      physicochemical properties of their aqueous solutions. The problem was tackled by
      using an extensive analysis of (13)C NMR data on the solutions of whole molecules
      and of simple precursors in addition to FT-IR investigation and molecular
      simulations. This analysis demonstrated that out of the many possible
      atropisomers, only a few are significantly populated, and their relative
      population is provided. The conformational analysis also indicated that the
      presence of a sterically hindered amidic bond, allowing a significant population
      of cis forms (E in iopromide and exo in iomeprol), may be the basis for an
      increased thermodynamic solubility of concentrated solutions of iomeprol. 

PMID- 25945973
TI  - Reactivity of Hydrated Monovalent First Row Transition Metal Ions [M(H2O)n](+), M
      = Cr, Mn, Fe, Co, Ni, Cu, and Zn, n < 50, Toward Acetonitrile.
AB  - Reactions of [M(H2O)n](+), M = Cr, Mn, Fe, Co, Ni, Cu, and Zn, n < 50, with CH3CN
      are studied in the gas phase by Fourier transform ion cyclotron resonance (FT
      ICR) mass spectrometry. Sequential uptake of 4-6 acetonitrile molecules is
      observed for all metals. Rate constants show a weak dependence on both the metal
      and the number of acetonitrile molecules already in the cluster. Nanocalorimetry
      yields the enthalpy of the first reaction step. For most metals, this is
      consistent with a ligand exchange of water against acetonitrile. For M = Cr,
      however, the strong exothermicity of DeltaE(nc) = -195 +/- 26 kJ mol(-1) suggests
      an electron transfer from Cr(+) to CH3CN. Exclusively for M = Zn, a relatively
      slow oxidation of the metal center to Zn(2+), with formation of ZnOH(+) and
      release of CH3CNH(*) or CH3CHN(*) is observed. Density functional theory
      molecular dynamics simulations and geometry optimizations show that charge
      transfer from Zn(+) to CH3CN as well as the subsequent proton transfer are
      associated with a barrier.

PMID- 25945971
TI  - DEK over-expression promotes mitotic defects and micronucleus formation.
AB  - The DEK gene encodes a nuclear protein that binds chromatin and is involved in
      various fundamental nuclear processes including transcription, RNA splicing, DNA
      replication and DNA repair. Several cancer types characteristically over-express
      DEK at the earliest stages of transformation. In order to explore relevant
      mechanisms whereby DEK supports oncogenicity, we utilized cancer databases to
      identify gene transcripts whose expression patterns are tightly correlated with
      that of DEK. We identified an enrichment of genes involved in mitosis and thus
      investigated the regulation and possible function of DEK in cell division.
      Immunofluorescence analyses revealed that DEK dissociates from DNA in early
      prophase and re-associates with DNA during telophase in human keratinocytes.
      Mitotic cell populations displayed a sharp reduction in DEK protein levels
      compared to the corresponding interphase population, suggesting DEK may be
      degraded or otherwise removed from the cell prior to mitosis. Interestingly, DEK
      overexpression stimulated its own aberrant association with chromatin throughout
      mitosis. Furthermore, DEK co-localized with anaphase bridges, chromosome
      fragments, and micronuclei, suggesting a specific association with mitotically
      defective chromosomes. We found that DEK over-expression in both non-transformed
      and transformed cells is sufficient to stimulate micronucleus formation. These
      data support a model wherein normal chromosomal clearance of DEK is required for
      maintenance of high fidelity cell division and chromosomal integrity. Therefore,
      the overexpression of DEK and its incomplete removal from mitotic chromosomes
      promotes genomic instability through the generation of genetically abnormal
      daughter cells. Consequently, DEK over-expression may be involved in the initial
      steps of developing oncogenic mutations in cells leading to cancer initiation. 

PMID- 25945972
TI  - Structural Basis Underlying the Binding Preference of Human Galectins-1, -3 and 
      7 for Galbeta1-3/4GlcNAc.
AB  - Galectins represent beta-galactoside-binding proteins and are known to bind
      Galbeta1-3/4GlcNAc disaccharides (abbreviated as LN1 and LN2, respectively).
      Despite high sequence and structural homology shared by the carbohydrate
      recognition domain (CRD) of all galectin members, how each galectin displays
      different sugar-binding specificity still remains ambiguous. Herein we provided
      the first structural evidence of human galectins-1, 3-CRD and 7 in complex with
      LN1. Galectins-1 and 3 were shown to have higher affinity for LN2 than for LN1,
      while galectin-7 displayed the reversed specificity. In comparison with the
      previous LN2-complexed structures, the results indicated that the average
      glycosidic torsion angle of galectin-bound LN1 (psi(LN1) ~ 135 degrees ) was
      significantly differed from that of galectin-bound LN2 (psi(LN2 )~ -108 degrees
      ), i.e. the GlcNAc moiety adopted a different orientation to maintain essential
      interactions. Furthermore, we also identified an Arg-Asp/Glu-Glu-Arg salt-bridge
      network and the corresponding loop (to position the second Asp/Glu residue)
      critical for the LN1/2-binding preference.

PMID- 25945975
TI  - [Does Brazil need a national surveillance system for death from tuberculosis?].

PMID- 25945974
TI  - Activity-Based Protein Profiling of Oncogene-Driven Changes in Metabolism Reveals
      Broad Dysregulation of PAFAH1B2 and 1B3 in Cancer.
AB  - Targeting dysregulated metabolic pathways is a promising therapeutic strategy for
      eradicating cancer. Understanding how frequently altered oncogenes regulate
      metabolic enzyme targets would be useful in identifying both broad-spectrum and
      targeted metabolic therapies for cancer. Here, we used activity-based protein
      profiling to identify serine hydrolase activities that were consistently
      upregulated by various human oncogenes. Through this profiling effort, we found
      oncogenic regulatory mechanisms for several cancer-relevant serine hydrolases and
      discovered that platelet activating factor acetylhydrolase 1B2 and 1B3 (PAFAH1B2
      and PAFAH1B3) activities were consistently upregulated by several oncogenes,
      alongside previously discovered cancer-relevant hydrolases fatty acid synthase
      and monoacylglycerol lipase. While we previously showed that PAFAH1B2 and 1B3
      were important in breast cancer, our most recent profiling studies have revealed
      that these enzymes may be dysregulated broadly across many types of cancers.
      Here, we find that pharmacological blockade of both enzymes impairs cancer
      pathogenicity across multiple different types of cancer cells, including breast,
      ovarian, melanoma, and prostate cancer. We also show that pharmacological
      blockade of PAFAH1B2 and 1B3 causes unique changes in lipid metabolism, including
      heightened levels of tumor-suppressing lipids. Our results reveal oncogenic
      regulatory mechanisms of several cancer-relevant serine hydrolases using activity
      based protein profiling, and we show that PAFAH1B2 and 1B3 are important in
      maintaining cancer pathogenicity across a wide spectrum of cancer types.

PMID- 25945976
TI  - [Foreign capital and the privatization of the Brazilian health system].

PMID- 25945977
TI  - [Effectiveness of physical exercise on fatigue in cancer patients during active
      treatment: a systematic review and meta-analysis].
AB  - This study aimed to determine the effectiveness of physical exercise in
      decreasing fatigue in cancer patients during active treatment. The PubMed
      Central, EMBASE, and OVID databases were consulted up to April 2014 to identify
      randomized clinical trials that evaluated the effect of exercise on fatigue in
      cancer patients undergoing active treatment. Eleven studies (n = 1,407) were
      included. Chemotherapy was the most common form of treatment (n = 1,028). The
      studies showed a low risk of bias and high methodological quality. Effect
      estimates showed that physical exercise significantly improved fatigue (SMD = 
      3.0; 95%CI: -5.21; -0.80), p < 0.0001. Similar effects were found for resistance
      training (SMD = -4.5; 95%CI: -7.24; -1.82), p = 0.001. Significant improvements
      were found in breast and prostate cancer patients (p < 0.05). Exercise is a safe
      and effective intervention in the management fatigue in cancer patients
      undergoing active treatment. 

PMID- 25945978
TI  - [Caffeine consumption during pregnancy and attention deficit hyperactivity
      disorder (ADHD): a systematic literature review].
AB  - This aim of this study was to conduct a systematic literature review on the
      association between maternal caffeine intake during pregnancy and attention
      deficit hyperactivity disorder (ADHD) in childhood. The systematic multiple-stage
      literature search in PubMed, LILACS, BIREME, and PsycINFO was limited to research
      in human subjects and published in Portuguese, English, and Spanish. A total of
      373 references were retrieved. Of these, only five met the study's objectives and
      were kept in the review. Most of the studies employed a longitudinal design, were
      conducted in developed countries, and were published in the last five years. Only
      one study found a positive association. Studies on caffeine consumption during
      pregnancy and ADHD are scarce, with conflicting results and several
      methodological difficulties such as lack of standardized outcome measures. 

PMID- 25945979
TI  - [Using Google Trends to estimate the incidence of influenza-like illness in
      Argentina].
AB  - The aim of this study was to find a model to estimate the incidence of influenza
      like illness (ILI) from the Google Trends (GT) related to influenza. ILI
      surveillance data from 2012 through 2013 were obtained from the National Health
      Surveillance System, Argentina. Internet search data were downloaded from the GT
      search engine database using 6 influenza-related queries: flu, fever, cough, sore
      throat, paracetamol, and ibuprofen. A Poisson regression model was developed to
      compare surveillance data and internet search trends for the year 2012. The
      model's results were validated using surveillance data for the year 2013 and
      results of the Google Flu Trends (GFT) tool. ILI incidence from the surveillance
      system showed strong correlations with ILI estimates from the GT model (r =
      0.927) and from the GFT tool (r = 0.943). However, the GFT tool overestimates (by
      nearly twofold) the highest ILI incidence, while the GT model underestimates the
      highest incidence by a factor of 0.7. These results demonstrate the utility of GT
      to complement influenza surveillance. 

PMID- 25945980
TI  - [Validity and reliability of a scale to assess self-efficacy for physical
      activity in elderly].
AB  - This study aimed to analyze the confirmatory factor validity and reliability of a
      self-efficacy scale for physical activity in a sample of 118 elderly (78% women)
      from 60 to 90 years of age. Mplus 6.1 was used to evaluate the confirmatory
      factor analysis. Reliability was tested by internal consistency and temporal
      stability. The original scale consisted of five items with dichotomous answers
      (yes/no), independently for walking and moderate and vigorous physical activity.
      The analysis excluded the item related to confidence in performing physical
      activities when on vacation. Two constructs were identified, called "self
      efficacy for walking" and "self-efficacy for moderate and vigorous physical
      activity", with a factor load >= 0.50. Internal consistency was adequate both for
      walking (> 0.70) and moderate and vigorous physical activity (> 0.80), and
      temporal stability was adequate for all the items. In conclusion, the self
      efficacy scale for physical activity showed adequate validity, reliability, and
      internal consistency for evaluating this construct in elderly Brazilians. 

PMID- 25945981
TI  - [What are the causes of death of patients with tuberculosis: multiple causes of
      death in a cohort of cases and a research proposal of presumed causes].
AB  - The objective of this study was to analyze the multiple causes of death in a
      cohort of patients with tuberculosis (TB) and to introduce an investigation
      proposal death for TB from a list of presumable causes. We performed a
      probabilistic record linkage with the databases of the Information System for
      Notifiable Diseases (SINAN) 2006 and the Mortality Information System (SIM) 2006
      2008. There were 825 deaths, of which 23% for death for TB, deaths due to TB with
      16% and 61% without mention of TB. Two hundred and fifteen (42.7%) deaths
      occurred within the period of treatment, whose profile differed from the pattern
      of causes when TB was an associated cause, with high frequency of respiratory
      diseases, AIDS and ill-defined causes. We elaborated a proposal for correction of
      associated causes of death and an investigation proposal death for TB from a list
      of presumable causes. According to the proposal, 26 deaths could have modified
      the underlying cause. This study highlights the importance of record linkage to
      TB surveillance and improvement of information the SIM and SINAN. 

PMID- 25945982
TI  - The perceptions of medical researchers on qualitative methodologies.
AB  - We aimed to verify doctor's perception of the qualitative research method, via a
      qualitative study of interviews with questions on the academic profile of doctors
      and on the methodology. We interviewed 42 professionals, of which 18 had
      experience with the qualitative method and 24 with the quantitative method. The
      results showed that knowledge on the qualitative method was virtually nil among
      "quantitative researchers", who did not value qualitative research, although some
      of those realized that it would be important to be more accepting in clinical
      practice. Others only considered the method as subsidiary to quantitative. The
      majority considered qualitative methods as lacking academic structure, taking too
      long to conduct empirical studies, and being difficult to publish. All of them
      criticized the misuse of the method, and the "quantitatives" pointed out the
      problem of being unable to reproduce. We concluded that widening the use of the
      qualitative method by doctors requires investment from the beginning of the
      academic career and participation in qualitative research projects. 

PMID- 25945983
TI  - [Prevalence of depression among firefighters].
AB  - Depression burder is high worldwide. Socioeconomic factors and exposure to
      extreme situations at work may be associated with the illness. This study focused
      on the prevalence of depression and associated factors among firefighters in Belo
      Horizonte, Minas Gerais State, Brazil. A cross-sectional study was conducted
      among male firefighters in Belo Horizonte (n = 711). The Beck Depression
      Inventory (BDI) was used to assess depression. Univariate and multivariate
      logistic regression models were used to study the association between socio
      demographic characteristics, occupational stressors, health status, and
      depression. Prevalence of depression in the sample was 5.5%. The likelihood of
      developing depression was higher among firefighters who reported post-traumatic
      stress symptoms (OR = 12.47; 95%CI: 5.64-27.57) and alcohol abuse (OR = 5.30;
      95%CI: 2.35-11.96). The results are discussed considering the interrelationships
      between mental disorders, the healthy worker effect, and social recognition of
      firefighters' work. 

PMID- 25945984
TI  - Hospitalizations of children due to primary health care sensitive conditions in
      Pernambuco State, Northeast Brazil.
AB  - Admissions due to primary health care sensitive conditions from 1999 to 2009
      among children < 5 years old were analyzed for municipalities in Pernambuco
      State, Brazil. Using data from the Brazilian Unified National Health System's
      Hospital Information System, a negative binomial regression was applied to
      estimate rate ratio (RR) and 95%CI for the effect on primary health care
      sensitive condition rates (admissions/10,000 inhabitants) of the Family Health
      Program (FHP) coverage (%), some demographic variables and living conditions.
      Hospitalizations due to primary health care sensitive conditions represented
      44.1% of 861,628 admissions and the rate declined from 557.6 to 318.9 (-42.8%), a
      reduction three times greater than the rate due to all other causes. Increased
      FHP coverage was protective against primary health care sensitive conditions (RR
      = 0.94; 95%CI: 0.89-0.99). A decline in hospitalizations due to primary health
      care sensitive conditions indicated improvements in health status and may be
      associated with the consolidation of primary health care. Studies on access and
      quality of primary health care in relation to child morbidity and
      hospitalizations are needed.

PMID- 25945985
TI  - [Economic cost of permanent disability caused by road traffic injuries in Mexico
      in 2012].
AB  - This study estimated the economic costs of permanent disability caused by road
      traffic injuries in Mexico during 2012. From the health system's perspective, a
      bottom-up approach was used to calculate direct medical costs (hospitalization,
      outpatient care, rehabilitation, and prostheses). From society's perspective,
      using a human capital approach, indirect costs were associated with loss of
      productivity for the victims and their caregivers. Permanent disability due to
      road traffic injuries takes a high toll on the health system and Mexican society.
      From the health system perspective, the cost was US$269,529,480.72, or
      US$1,496.33 per victim. The estimated average cost to society was US$3,445.45
      during the first year. The total average cost per victim was US$4,941.77,
      resulting in a total economic cost of US$1,119,761,632.53 during 2012. The
      study's findings highlight the need to design and implement more rigorous and
      efficient public policies to control and prevent road traffic injuries in Mexico.

PMID- 25945986
TI  - [Violence and social distress among transgender persons in Santa Maria, Rio
      Grande do Sul State, Brazil].
AB  - The authors conducted an ethnographic research with transgender persons in Santa
      Maria, Rio Grande do Sul State, Brazil, in 2012, using participant observation,
      semi-structured interviews, and following their everyday lives. These individuals
      invariably experienced physical and symbolic violence and the resulting distress,
      a condition they had to deal with in their careers and daily practices and tasks.
      The article discusses the violence experienced by transvestites (in the family,
      school, police precincts, and health services), specifically seeking to
      understand how such violence relates to their experiences with health services
      and how the latter respond. 

PMID- 25945987
TI  - Energy intake underreporting of adults in a household survey: the impact of using
      a population specific basal metabolic rate equation.
AB  - The purpose of the present study was to identify energy intake (EI)
      underreporting and to estimate the impact of using a population specific equation
      for the basal metabolic rate (BMR) in a probability sample of adults from
      Niteroi, Rio de Janeiro State, Brazil. A sample of 1,726 subjects participated in
      the study. EI was assessed by a 24-hour dietary recall and EI/BMR was computed
      with BMR estimated using internationally recommended equations as well as
      specific equations developed for the adult population of Niteroi. Mean EI was
      1,570.9 and 2,188.8 kcal.day-1 for women and men, respectively. EI decreased with
      increasing age in both men and women. BMR estimated by the Brazilian equation was
      significantly lower than the values estimated by the international equation for
      all age, sex and nutritional status groups. In general, EI underreporting was
      found in at least 50% of the population, higher in women, and increased with
      increasing age and body mass index (BMI). The results of the present study
      confirm that EI is underreported, even when BMR is estimated using population
      specific equations.

PMID- 25945988
TI  - [Self-assessment of health status and associated factors: a study in bank
      workers].
AB  - The aim of this study was to determine how bank employees assess their health
      status and risk factors associated with this indicator in this population. This
      is a cross-sectional study involving 525 workers of a banking system in the State
      of Espirito Santo, Brazil. The magnitude of the associations was assessed using
      logistic regression hierquizada in levels. It was found that 17% (n = 87) of bank
      self-rated their health status as fair or poor. Were associated with worse self
      assessed health of the low socioeconomic level (OR = 1.80; 95%CI: 1.06-3.05), the
      sedentary lifestyle (OR = 2.64; 95%CI: 1.42-4.89), the excess weight (OR = 3.18;
      95%CI: 1.79-5.65), low social support (OR = 3.71; 95%CI: 2.10-6.58), and the
      presence of chronic diseases (OR = 5,49; 95%CI: 2.46-12.27). It is concluded
      that, compared with other locations, there was a significant number of banking
      that self-rated their health status as fair or poor, and that the presence of
      chronic diseases was presented as the factor with the greatest impact on how the
      individual evaluates their own health. 

PMID- 25945989
TI  - An evaluation of quality of life and its determinants among people living with
      HIV/AIDS from Southern Brazil.
AB  - This cross-sectional study evaluated the quality of life and its associated
      factors among people living with HIV/AIDS at a regional reference center for the
      treatment of HIV/AIDS in southern Brazil. WHOQOL-HIV Bref, ASSIST 2.0, HAD Scale,
      and a questionnaire were used to assess 625 participants on quality of life,
      clinical and sociodemographic characteristics, drug use, depression and anxiety.
      Multivariate analysis was performed through linear regression. The lowest results
      for quality of life were associated with being female, age (< 47 years), low
      education levels, low socioeconomic class, unemployment, not having a stable
      relationship, signs of anxiety and depression, abuse or addiction of psychoactive
      substances, lack of perceived social support, never taking antiretroviral
      medication, lipodystrophy, comorbidities, HIV related hospitalizations and a CD4+
      cell count less than 350. Psychosocial factors should be included in the physical
      and clinical evaluation given their strong association with quality of life
      domains. 

PMID- 25945990
TI  - [Prevalence of intimate partner physical violence in men and women from
      Florianopolis, Santa Catarina State, Brazil: a population-based study].
AB  - This study investigated the association between gender and intimate partner
      physical violence. A random cluster sample was chosen as the baseline cohort
      population in a cross-sectional design. Lifetime prevalence rates were as
      follows: any physical violence (17%), moderate physical violence (16.6%), and
      severe physical violence (7.3%). There were no significant differences between
      genders in moderate physical violence, but women were more likely to suffer
      severe abuse. Logistic regression was used to identify associations between
      violence and gender, adjusting for exploratory variables. Women that were older,
      widowed/separated, had less schooling or lower income, and African-descendants
      were all more likely to have suffered intimate partner violence. Prevalence of
      severe physical violence experienced by men only changed significantly according
      to marital status. Alcohol abuse by women increased the odds of suffering
      physical violence.

PMID- 25945991
TI  - Quality of life of mothers whose children work on the streets of Sao Paulo,
      Brazil.
AB  - The present study evaluated the perceived quality of life of the mothers of
      street children and investigated the association with their history of childhood
      violence, the occurrence of current domestic violence, their current mental
      states and that of their children, and family functioning. The applied
      instruments were as follows: Strengths and Difficulties Questionnaire,
      WorldSAFECore Questionnaire, Instrument for the Assessment of Quality of Life of
      the WHO, Global Assessment of Relational Functioning Scale, Childhood Trauma
      Questionnaire and a socio-demographic questionnaire. The sample of convenience
      consisted of 79 low-income mothers who raised their children alone, and most of
      whom had a positive screening for mental illness. The multiple regression
      analysis showed that the perception of quality of life of these women was
      associated with the presence of psychopathology either in themselves or their
      children and family dysfunction. Thus any program aimed at improving the quality
      of life of such mothers should consider addressing their mental problems as well
      as those of their children, besides offering educational and psychotherapeutic
      approaches to these families to improve the social environment. 

PMID- 25945992
TI  - [The meaning of "individual" social capital for diabetics receiving care in a
      Colombian city].
AB  - The aim of this study was to understand the meaning of social capital in relation
      to type 2 diabetes according to gender, within an urban setting in Colombia,
      based on a qualitative design for symbolic interactionism. Twenty-four women and
      16 men with diabetes, family members, and healthcare personnel participated in
      six focus groups. A total of 850 codes emerged that comprised a set of 142 codes
      for ego, alter, and alter ego. Three categories and 20 subcategories were
      identified for the "coding paradigm design". The meaning differed between men and
      women. Social ties in social networks, created daily through trust and solidarity
      for care, were valued differently due to the social experiences and events
      resulting from self-confidence, self-efficacy for social support, and mainly self
      esteem vis-a-vis management and control of the disease. An individual's social
      resources are reified for the management and care of the disease as a strategy to
      mitigate health inequalities. 

PMID- 25945993
TI  - Mortality from Alzheimer's disease in Brazil, 2000-2009.
AB  - Alzheimer's disease is the most prevalent type of dementia in the elderly
      worldwide. To evaluate the mortality trend from Alzheimer's disease in Brazil, a
      descriptive study was conducted with the Mortality Information System of the
      Brazilian Ministry of Health (2000-2009). Age and sex-standardized mortality
      rates were calculated in Brazil's state capitals, showing the percentage
      variation by exponential regression adjustment. The state capitals as a whole
      showed an annual growth in mortality rates in the 60 to 79 year age bracket of
      8.4% in women and 7.7% in men. In the 80 and older age group, the increase was
      15.5% in women and 14% in men. Meanwhile, the all-cause mortality rate declined
      in both elderly men and women. The increase in mortality from Alzheimer's disease
      occurred in the context of chronic diseases as a proxy for increasing prevalence
      of the disease in the population. The authors suggest healthcare strategies for
      individuals with chronic non-communicable diseases.

PMID- 25945994
TI  - [Decentralization of epidemiological surveillance in Pernambuco State, Brazil].
AB  - The study aimed to analyze the relationship between decentralization of the
      Brazilian Unified National Health System (SUS) and the development of
      epidemiological surveillance activities in municipalities (counties) in
      Pernambuco State, Brazil. This was an exploratory descriptive qualitative and
      quantitative study, including a document search, completion of semi-structured
      interviews by key informants, and an ecological spatial and time trend study of
      selected health indicators, covering a 10-year period (2001-2010). The study
      showed that municipalities adhered to the decentralization process, which was
      making progress in Pernambuco, but with inequalities and weaknesses in its
      development. There was also a fluctuation in the time series for the selected
      indicators. Thus, even though the decentralization of epidemiological
      surveillance is still incipient in some municipalities, their protagonist role in
      implementing the activities promotes empowerment at the local level by producing
      key information for decision-making. 

PMID- 25945995
TI  - [Family configuration and physical and psychological health status in a sample of
      elderly].
AB  - This study focused on the relations between family configuration (living
      arrangements, heads of family, and financial contributions to the family's
      support), age, gender, and physical health (functional capacity, number of
      diseases and signs and symptoms, and social involvement) and psychological health
      (depression and anxiety) among the elderly, based on self-reported data. The
      probabilistic sample included 134 elderly without cognitive deficit, with data
      collected in home interviews. Cluster analyses were performed using the
      partitioning method (three groupings). The variables that contributed the most to
      forming groups were basic activities of daily living (R(2) = 0.732) and
      instrumental activities of daily living (R(2) = 0.487), number of diseases (R(2)
      = 0.241), and age (R(2) = 0.225). The predominant family configuration was living
      with children and/or grandchildren, with the elderly as providers and heads of
      the family. The study showed associations between family configuration and
      physical and psychological health status. Women showed a higher financial burden
      and worse psychological health than men.

PMID- 25945996
TI  - Validity of pre and post-term birth rates based on the date of last menstrual
      period compared to early obstetric ultrasonography.
AB  - The aim of this study was to assess the validity of the last menstrual period
      (LMP) estimate in determining pre and post-term birth rates, in a prenatal cohort
      from two Brazilian cities, Sao Luis and Ribeirao Preto. Pregnant women with a
      single fetus and less than 20 weeks' gestation by obstetric ultrasonography who
      received prenatal care in 2010 and 2011 were included. The LMP was obtained on
      two occasions (at 22-25 weeks gestation and after birth). The sensitivity of LMP
      obtained prenatally to estimate the preterm birth rate was 65.6% in Sao Luis and
      78.7% in Ribeirao Preto and the positive predictive value was 57.3% in Sao Luis
      and 73.3% in Ribeirao Preto. LMP errors in identifying preterm birth were lower
      in the more developed city, Ribeirao Preto. The sensitivity and positive
      predictive value of LMP for the estimate of the post-term birth rate was very low
      and tended to overestimate it. LMP can be used with some errors to identify the
      preterm birth rate when obstetric ultrasonography is not available, but is not
      suitable for predicting post-term birth. 

PMID- 25945999
TI  - Human and Murine Clonal CD8+ T Cell Expansions Arise during Tuberculosis Because
      of TCR Selection.
AB  - The immune system can recognize virtually any antigen, yet T cell responses
      against several pathogens, including Mycobacterium tuberculosis, are restricted
      to a limited number of immunodominant epitopes. The host factors that affect
      immunodominance are incompletely understood. Whether immunodominant epitopes
      elicit protective CD8+ T cell responses or instead act as decoys to subvert
      immunity and allow pathogens to establish chronic infection is unknown. Here we
      show that anatomically distinct human granulomas contain clonally expanded CD8+ T
      cells with overlapping T cell receptor (TCR) repertoires. Similarly, the murine
      CD8+ T cell response against M. tuberculosis is dominated by TB10.44-11-specific
      T cells with extreme TCRbeta bias. Using a retro genic model of TB10.44-11
      specific CD8+ Tcells, we show that TCR dominance can arise because of competition
      between clonotypes driven by differences in affinity. Finally, we demonstrate
      that TB10.4-specific CD8+ T cells mediate protection against tuberculosis, which
      requires interferon-gamma production and TAP1-dependent antigen presentation in
      vivo. Our study of how immunodominance, biased TCR repertoires, and protection
      are inter-related, provides a new way to measure the quality of T cell immunity,
      which if applied to vaccine evaluation, could enhance our understanding of how to
      elicit protective T cell immunity.

PMID- 25946001
TI  - Securing mobile ad hoc networks using danger theory-based artificial immune
      algorithm.
AB  - A mobile ad hoc network (MANET) is a set of mobile, decentralized, and self
      organizing nodes that are used in special cases, such as in the military. MANET
      properties render the environment of this network vulnerable to different types
      of attacks, including black hole, wormhole and flooding-based attacks. Flooding
      based attacks are one of the most dangerous attacks that aim to consume all
      network resources and thus paralyze the functionality of the whole network.
      Therefore, the objective of this paper is to investigate the capability of a
      danger theory-based artificial immune algorithm called the mobile dendritic cell
      algorithm (MDCA) to detect flooding-based attacks in MANETs. The MDCA applies the
      dendritic cell algorithm (DCA) to secure the MANET with additional improvements.
      The MDCA is tested and validated using Qualnet v7.1 simulation tool. This work
      also introduces a new simulation module for a flooding attack called the resource
      consumption attack (RCA) using Qualnet v7.1. The results highlight the high
      efficiency of the MDCA in detecting RCAs in MANETs. 

PMID- 25946000
TI  - Drug repositioning for diabetes based on 'omics' data mining.
AB  - Drug repositioning has shorter developmental time, lower cost and less safety
      risk than traditional drug development process. The current study aims to
      repurpose marketed drugs and clinical candidates for new indications in diabetes
      treatment by mining clinical 'omics' data. We analyzed data from genome wide
      association studies (GWAS), proteomics and metabolomics studies and revealed a
      total of 992 proteins as potential anti-diabetic targets in human. Information on
      the drugs that target these 992 proteins was retrieved from the Therapeutic
      Target Database (TTD) and 108 of these proteins are drug targets with drug
      projects information. Research and preclinical drug targets were excluded and 35
      of the 108 proteins were selected as druggable proteins. Among them, five
      proteins were known targets for treating diabetes. Based on the pathogenesis
      knowledge gathered from the OMIM and PubMed databases, 12 protein targets of 58
      drugs were found to have a new indication for treating diabetes. CMap
      (connectivity map) was used to compare the gene expression patterns of cells
      treated by these 58 drugs and that of cells treated by known anti-diabetic drugs
      or diabetes risk causing compounds. As a result, 9 drugs were found to have the
      potential to treat diabetes. Among the 9 drugs, 4 drugs (diflunisal, nabumetone,
      niflumic acid and valdecoxib) targeting COX2 (prostaglandin G/H synthase 2) were
      repurposed for treating type 1 diabetes, and 2 drugs (phenoxybenzamine and
      idazoxan) targeting ADRA2A (Alpha-2A adrenergic receptor) had a new indication
      for treating type 2 diabetes. These findings indicated that 'omics' data mining
      based drug repositioning is a potentially powerful tool to discover novel anti
      diabetic indications from marketed drugs and clinical candidates. Furthermore,
      the results of our study could be related to other disorders, such as Alzheimer's
      disease. 

PMID- 25946002
TI  - Generation and Imaging of Transgenic Mice that Express G-CaMP7 under a
      Tetracycline Response Element.
AB  - The spatiotemporally controlled expression of G-CaMP fluorescent calcium
      indicator proteins can facilitate reliable imaging of brain circuit activity.
      Here, we generated a transgenic mouse line that expresses G-CaMP7 under a
      tetracycline response element. When crossed with a forebrain-specific
      tetracycline-controlled transactivator driver line, the mice expressed G-CaMP7 in
      defined cell populations in a tetracycline-controlled manner, notably in
      pyramidal neurons in layer 2/3 of the cortex and in the CA1 area of the
      hippocampus; this expression allowed for imaging of the in vivo activity of these
      circuits. This mouse line thus provides a useful genetic tool for controlled G
      CaMP expression in vivo. 

PMID- 25946004
TI  - Quantum plasmonics, gain and spasers: general discussion.

PMID- 25946003
TI  - IL-11 Attenuates Liver Ischemia/Reperfusion Injury (IRI) through STAT3 Signaling
      Pathway in Mice.
AB  - BACKGROUND: The protective role of IL-11, an IL-6 family cytokine, has been
      implicated in ischemia/reperfusion injury (IRI) in the heart and kidney, but its
      role has not been elucidated in liver IRI. This study was designed to evaluate
      the effects of IL-11 and its mechanism of action on liver IRI in a mouse model.
      METHODS: A partial (70%) warm liver IRI was induced by interrupting the
      artery/portal vein blood supply to the left/middle liver lobes. IL-11 mRNA
      expression of ischemic liver after reperfusion was analyzed. Signal transducer
      and activator of transcription 3 (STAT3) was analyzed following IL-11 treatment
      in vivo and in vitro. Next, IL-11 was injected intraperitoneally (ip) 1 hour
      before ischemia. Liver injury was assessed based on serum alanine
      aminotransferase levels and histopathology. Apoptosis and inflammation were also
      determined in the ischemic liver. To analyze the role of STAT3 in IL-11
      treatment, STAT3 siRNA or non-specific (NS) siRNA was used in vitro and in vivo.
      RESULTS: IL-11 mRNA expression was significantly increased after reperfusion in
      the ischemic liver. STAT3, as a target of IL-11, was activated in hepatocytes
      after IL-11 treatment in vivo and in vitro. Next, effects of IL-11/STAT3
      signaling pathway were assessed in liver IRI, which showed IL-11 treatment
      significantly attenuated liver IRI, as evidenced by reduced hepatocellular
      function and hepatocellular necrosis/apoptosis. In addition, IL-11 treatment
      significantly inhibited the gene expressions of pro-inflammatory cytokines (TNF
      alpha and IL-10) and chemokines (IP-10 and MCP-1). To determine the role of STAT3
      in the hepatoprotective effects of IL-11, STAT3 siRNA or NS siRNA was used prior
      to IL-11 treatment. The results showed STAT3 knockdown abrogated the protective
      effects of IL-11 in vitro and in vivo. CONCLUSIONS: This work provides first-time
      evidence for the protective effect of IL-11 treatment on hepatocyte in liver IRI,
      through the activation of the STAT3 pathway.

PMID- 25946005
TI  - NMR-Based Metabolomic Study on Isatis tinctoria: Comparison of Different
      Accessions, Harvesting Dates, and the Effect of Repeated Harvesting.
AB  - Isatis tinctoria is an ancient dye and medicinal plant with potent anti
      inflammatory and antiallergic properties. Metabolic differences were investigated
      by NMR spectroscopy of accessions from different origins that were grown under
      identical conditions on experimental plots. For these accessions, metabolite
      profiles at different harvesting dates were analyzed, and single and repeatedly
      harvested plants were compared. Leaf samples were shock-frozen in liquid N2
      immediately after being harvested, freeze-dried, and cryomilled prior to
      extraction. Extracts were prepared by pressurized liquid extraction with ethyl
      acetate and 70% aqueous methanol. NMR spectra were analyzed using a combination
      of different methods of multivariate data analysis such as principal component
      analysis (PCA), canonical analysis (CA), and k-nearest neighbor concept (k-NN).
      Accessions and harvesting dates were well separated in the PCA/CA/k-NN analysis
      in both extracts. Pairwise statistical total correlation spectroscopy (STOCSY)
      revealed unsaturated fatty acids, porphyrins, carbohydrates, indole derivatives,
      isoprenoids, phenylpropanoids, and minor aromatic compounds as the cause of these
      differences. In addition, the metabolite profile was affected by the repeated
      harvest regime, causing a decrease of 1,5-anhydroglucitol, sucrose, unsaturated
      fatty acids, porphyrins, isoprenoids, and a flavonoid. 

PMID- 25946006
TI  - The Role of Neighborhood Environment in Promoting Risk Factors of Cardiovascular
      Disease among Young Adults: Data from Middle to High Income Population in an
      Asian Megacity.
AB  - BACKGROUND: Modifiable risk factors of cardiovascular diseases (CVD) have their
      triggers in the neighborhood environments of communities. Studying the
      environmental triggers for CVD risk factors is important to understand the
      situation in a broader perspective. Young adults are influenced the most by the
      environment profile around them hence it is important to study this subset of the
      population. METHODS: This was a descriptive study conducted using the EPOCH
      research tool designed by the authors of the PURE study. The study population
      consisted of young adults aged 18-25 in two areas of Karachi. The study setting
      was busy shopping malls frequented by young adults in the particular community
      being studied. RESULTS: Our total sample size was 120 individuals, who consented
      to be interviewed by our interviewers. Less than 50% of the population recognized
      some form of restriction regarding smoking in their communities. The largest
      contributor to tobacco advertising was actors smoking in movies and TV shows with
      89% responses from both communities. Only 11.9% of the individuals disapproved of
      smoking cigarettes among men with wide acceptance of 'sheesha' across all age
      groups. Advertising for smoking and junk food was more frequent as compared to
      smoking cessation, healthy diet and exercise in both the areas. Unhealthy food
      items were more easily available in contrast to healthier options. The cost of
      healthy snack food options including vegetables and fruits was higher than sugary
      drinks and foods. CONCLUSION: This assessment showed that both communities were
      exposed to environments that promote risk factors for cardiovascular diseases.

PMID- 25946007
TI  - Ablative Fractional Carbon Dioxide Laser in the Treatment of Chronic,
      Posttraumatic, Lower-Extremity Ulcers in Elderly Patients.
AB  - IMPORTANCE: Treating posttraumatic lower extremity wounds can be challenging,
      especially in elderly patients. Recently, the use of fractional carbon dioxide
      laser has been shown to improve wound healing in scar-related wounds. We used
      this treatment modality in posttraumatic wounds that were slow to heal in 3
      elderly patients. OBSERVATIONS: Each wound underwent one fractional carbon
      dioxide laser treatment. The wound base was treated at 30 mJ and 5% density. The
      entire wound edge and 1 to 2 cm into the normal surrounding skin were treated at
      50 mJ and 5% density. One pass was completed at 150 Hz per treatment. Treatments
      were well tolerated with only mild discomfort. Each wound healed by 60% or
      greater within 3 weeks. No adverse events were reported aside from mild and
      transient erythema at site of treatment. CONCLUSIONS AND RELEVANCE: Fractional
      carbon dioxide laser treatment appeared to accelerate healing in each of these
      posttraumatic wounds. It may be a helpful adjunct in nonhealing posttraumatic
      wounds.

PMID- 25946008
TI  - Single Cell Quantification of Reporter Gene Expression in Live Adult
      Caenorhabditis elegans Reveals Reproducible Cell-Specific Expression Patterns and
      Underlying Biological Variation.
AB  - In multicellular organisms such as Caenorhabditis elegans, differences in complex
      phenotypes such as lifespan correlate with the level of expression of particular
      engineered reporter genes. In single celled organisms, quantitative understanding
      of responses to extracellular signals and of cell-to-cell variation in responses
      has depended on precise measurement of reporter gene expression. Here, we
      developed microscope-based methods to quantify reporter gene expression in cells
      of Caenorhabditis elegans with low measurement error. We then quantified
      expression in strains that carried different configurations of Phsp-16.2
      fluorescent-protein reporters, in whole animals, and in all 20 cells of the
      intestine tissue, which is responsible for most of the fluorescent signal. Some
      animals bore more recently developed single copy Phsp-16.2 reporters integrated
      at defined chromosomal sites, others, "classical" multicopy reporter gene arrays
      integrated at random sites. At the level of whole animals, variation in gene
      expression was similar: strains with single copy reporters showed the same amount
      of animal-to-animal variation as strains with multicopy reporters. At the level
      of cells, in animals with single copy reporters, the pattern of expression in
      cells within the tissue was highly stereotyped. In animals with multicopy
      reporters, the cell-specific expression pattern was also stereotyped, but
      distinct, and somewhat more variable. Our methods are rapid and gentle enough to
      allow quantification of expression in the same cells of an animal at different
      times during adult life. They should allow investigators to use changes in
      reporter expression in single cells in tissues as quantitative phenotypes, and
      link those to molecular differences. Moreover, by diminishing measurement error,
      they should make possible dissection of the causes of the remaining, real,
      variation in expression. Understanding such variation should help reveal its
      contribution to differences in complex phenotypic outcomes in multicellular
      organisms. 

PMID- 25946009
TI  - Selective vs Nonselective Nonsteroidal Anti-inflammatory Drugs and Anastomotic
      Leakage After Colorectal Surgery.

PMID- 25946010
TI  - Visible to Near-Infrared Emission from Ln(III)(Bis-oxazoline)-[Mo(V)(CN)8] (Ln =
      Ce-Yb) Magnetic Coordination Polymers Showing Unusual Lanthanide-Dependent
      Sliding of Cyanido-Bridged Layers.
AB  - Complexes of lanthanides(III) (Ce-Yb) with 2,2'-bis(2-oxazoline) (Box) combined
      with octacyanidomolybdate(V) gave a series of magneto-luminescent coordination
      polymers, {[Ln(III)(Box)n(DMF)m][Mo(V)(CN)8]}.x(solvent) (1-12). They are built
      of cyanido-bridged layers of a mixed 4- and 8-metal rings topology and show
      unique sliding of layers dependent on a 4f metal ion. For light lanthanides,
      dominant phase A, {[Ln(III)(Box)2(DMF)2][Mo(V)(CN)8]}.1.5MeCN (Ln = Ce, 1; Pr, 2;
      Nd, 3), consists of ideally aligned, not shifted layers, giving large channels
      (13.7 * 14.0 A). Intermediate lanthanides reveal phase B, {[Ln(III)(Box)2(DMF)2]
      [Mo(V)(CN)8]}.H2O (Ln = Sm, 4; Eu, 5; Gd, 6; Tb, 7; Dy, 8), of smaller pores (8.4
      * 10.6 A) due to layer-H2O hydrogen bonding, which induces sliding of CN(-)
      bridged layers. Heavy lanthanides show phase C,
      {[Ln(III)(Box)(DMF)3][Mo(V)(CN)8]}.MeCN (Ln = Ho, 9; Er, 10; Tm, 11; Yb, 12),
      with large channels (13.7 * 13.7 A) of a similar size to light lanthanides. This
      effect comes from the changes in Ln(III) coordination sphere affecting solvent
      layer interactions. Compounds 1-12 reveal diverse emission depending on the
      interaction between Ln(III) and Box luminophors. For 2-5, 9, and 12, the ligand
      to-metal energy-transfer-induced visible f-centered emission ranging from green
      for Ho(III)-based 9, orange from Sm(III)-based 4, to red for Pr(III)- and Eu(III)
      containing 2 and 5, respectively. Near-infrared emission was found for 2-4, 9,
      and 12. Red phosphorescence of Box was detected for Gd(III)-based 6, whereas the
      selective excitation of ligand or Ln(III) excited states resulting in the
      switchable red to green emission was found for Tb(III)-based 7. The materials
      revealed Ln(III)-Mo(V) magnetic coupling leading to ferromagnetism below 2.0 and
      2.2 K for 4 and 7, respectively. The onset of magnetic ordering at low
      temperatures was found for 6 and 8. Compounds 1-12 form a unique family of
      cyanido-bridged materials of a bifunctional magneto-luminescence character
      combined with dynamic structural features. 

PMID- 25946011
TI  - Determinants of End-of-Life Expenditures in Patients with Oral Cancer in Taiwan:
      A Population-Based Study.
AB  - BACKGROUND: To investigate the association of basic demographic data,
      socioeconomic status, medical services, and hospital characteristics with end-of
      life expenditure in patients with oral cancer in Taiwan who died between 2009 to
      2011. METHODS: This nationwide population-based, retrospective cohort study
      identified 5,386 patients who died from oral cancer. We evaluated medical cost in
      the last month of life by universal health insurance. The impact of each variable
      on the end-of-life expenditure was examined by hierarchical generalized linear
      model (HGLM) using a hospital-level random-intercept model. RESULTS: The mean
      medical cost in the last six months of life was $2,611+/-3,329 (U.S. dollars). In
      HGLM using a random-intercept model, we found that patients younger than 65 years
      had an additional cost of $819 over those aged >=65 years. Patients who had a
      high Charlson Comorbidity Index Score (CCIS) had an additional $616 cost over
      those with a low CCIS. Those who survived post-diagnosis less than 6 months had
      an additional $659 in expenses over those who survived more than 24 months.
      Medical cost was $249 more for patients who had medium to high individual SES,
      and $319 more for those who were treated by non-oncologists. CONCLUSION: This
      study provides useful information for decision makers in understanding end-of
      life expenditure in oral cancer. We found significantly increased end-of-life
      expenditure in patients if they were younger than 65 years or treated by non
      oncologists, or had high CCIS, medium to high individual SES, and survival of
      less than 6 months after diagnosis.

PMID- 25946012
TI  - Regulating extracellular proteostasis capacity through the unfolded protein
      response.
AB  - The extracellular aggregation of proteins into proteotoxic oligomers and amyloid
      fibrils is implicated in the onset and pathology of numerous diseases referred to
      as amyloid diseases. All of the proteins that aggregate extracellularly in
      association with amyloid disease pathogenesis originate in the endoplasmic
      reticulum (ER) and are secreted through the secretory pathway. Disruptions in ER
      protein homeostasis or proteostasis (i.e., ER stress) can facilitate the aberrant
      secretion of misfolded protein conformations to the extracellular space and
      exacerbate pathologic protein aggregation into proteotoxic species. Activation of
      an ER stress-responsive signaling pathway, the Unfolded Protein Response (UPR),
      restores ER proteostasis through the transcriptional regulation of ER
      proteostasis pathways. In contrast, the functional role for the UPR in regulating
      extracellular proteostasis during ER stress is poorly defined. We recently
      identified ERdj3 as a UPR-regulated secreted chaperone that increases
      extracellular proteostasis capacity in response to ER stress, revealing a
      previously-unanticipated direct mechanism by which the UPR impacts extracellular
      proteostasis. Here, we discuss the functional implications of ERdj3 secretion on
      extracellular proteostasis maintenance and define the mechanisms by which ERdj3
      secretion coordinates intra- and extracellular proteostasis environments during
      ER stress. 

PMID- 25946013
TI  - Localization and Distribution of 'Candidatus Liberibacter asiaticus' in Citrus
      and Periwinkle by Direct Tissue Blot Immuno Assay with an Anti-OmpA Polyclonal
      Antibody.
AB  - 'Candidatus Liberibacter asiaticus' (CaLas), a non-cultured member of the alpha
      proteobacteria, is the causal agent of citrus Huanglongbing (HLB). Due to the
      difficulties of in vitro culture, antibodies against CaLas have not been widely
      used in studies of this pathogen. We have used an anti-OmpA polyclonal antibody
      based direct tissue blot immunoassay to localize CaLas in different citrus
      tissues and in periwinkle leaves. In citrus petioles, CaLas was unevenly
      distributed in the phloem sieve tubes, and tended to colonize in phloem sieve
      tubes on the underside of petioles in preference to the upper side of petioles.
      Both the leaf abscission zone and the junction of the petiole and leaf midrib had
      fewer CaLas bacteria compared to the main portions of the petiole and the
      midribs. Colonies of CaLas in phloem sieve tubes were more frequently found in
      stems with symptomatic leaves than in stems with asymptomatic leaves with an
      uneven distribution pattern. In serial sections taken from the receptacle to the
      peduncle, more CaLas were observed in the peduncle sections adjacent to the stem.
      In seed, CaLas was located in the seed coat. Many fewer CaLas were found in the
      roots, as compared to the seeds and petioles when samples were collected from
      trees with obvious foliar symptoms. The direct tissue blot immuno assay was
      adapted to whole periwinkle leaves infected by CaLas. The pathogen was
      distributed throughout the lateral veins and the results were correlated with
      results of qPCR. Our data provide direct spatial and anatomical information for
      CaLas in planta. This simple and scalable method may facilitate the future
      research on the interaction of CaLas and host plant. 

PMID- 25946014
TI  - More meditation, less habituation? The effect of mindfulness practice on the
      acoustic startle reflex.
AB  - BACKGROUND: Mindfulness as a mode of sustained and receptive attention promotes
      openness to each incoming stimulus, even if repetitive and/or aversive. Mindful
      attention has been shown to attenuate sensory habituation in expert meditators;
      however, others were not able to replicate this effect. The present study used
      acoustic startle reflex to investigate the effect of mindfulness practice
      intensity on sensory habituation. METHODS: Auditory Startle Response (ASR) to 36
      startling probes (12 trials x 3 block with 40 ms inter-block intervals), was
      measured using electromyography (EMG) in three groups of participants (N =
      12/group): meditation-naive, moderate practice, and intensive practice. RESULTS:
      Intensive practice group showed attenuated startle habituation as evidenced by
      significantly less habituation over the entire experiment relative to the
      meditation-naive and moderate practice groups. Furthermore, there was a
      significant linear effect showing between-block habituation in meditation-naive
      and moderate practice groups, but not in the intensive practice group. However,
      the Block x Group interaction between the intensive practice and the meditation
      naive groups was not significant. Moderate practice group was not significantly
      different from the meditation-naive in the overall measure of habituation, but
      showed significantly stronger habituation than both meditation-naive and
      intensive practice groups in Block 1. Greater practice intensity was
      significantly correlated with slower overall habituation and habituation rate in
      Blocks 2 and 3 in the intensive, but not in the moderate, practice group.
      CONCLUSIONS: The study provides tentative evidence that intensive mindfulness
      practice attenuates acoustic startle habituation as measured by EMG, but the
      effect is modest.Moderate practice, on the other hand, appears to enhance
      habituation, suggesting the effect of mindfulness practice on startle habituation
      might be non-linear [corrected] . Better understanding of the effect of mindful
      attention on startle habituation may shed new light on sensory information
      processing capacity of the human brain and its potential for de-automatisation of
      hard-wired processes.

PMID- 25946015
TI  - Cesium Toxicity Alters MicroRNA Processing and AGO1 Expressions in Arabidopsis
      thaliana.
AB  - MicroRNAs (miRNAs) are short RNA fragments that play important roles in
      controlled gene silencing, thus regulating many biological processes in plants.
      Recent studies have indicated that plants modulate miRNAs to sustain their
      survival in response to a variety of environmental stimuli, such as biotic
      stresses, cold, drought, nutritional starvation, and toxic heavy metals. Cesium
      and radio-cesium contaminations have arisen as serious problems that both impede
      plant growth and enter the food chain through contaminated plants. Many studies
      have been performed to define plant responses against cesium intoxication.
      However, the complete profile of miRNAs in plants during cesium intoxication has
      not been established. Here we show the differential expression of the miRNAs that
      are mostly down-regulated during cesium intoxication. Furthermore, we found that
      cesium toxicity disrupts both the processing of pri-miRNAs and AGONOUTE 1 (AGO1)
      mediated gene silencing. AGO 1 seems to be especially destabilized by cesium
      toxicity, possibly through a proteolytic regulatory pathway. Our study presents a
      comprehensive profile of cesium-responsive miRNAs, which is distinct from that of
      potassium, and suggests two possible mechanisms underlying the cesium toxicity on
      miRNA metabolism. 

PMID- 25946016
TI  - Oxidative stress-related liver dysfunction by sodium arsenite: Alleviation by
      Pistacia lentiscus oil.
AB  - CONTEXT: Pistacia lentiscus L. (Anacardiaceae) is an evergreen shrub widely
      distributed throughout the Mediterranean region. Pistacia lentiscus oil (PLo) was
      particularly known in North African traditional medicine. Thus, people of these
      regions have used it externally to treat sore throats, burns and wounds, as well
      as they employed it internally for respiratory allergies. PLo is rich in
      essential fatty acids, vitamin E and polyphenols. As a very active site of
      metabolism, liver is reported to be susceptible to arsenic (As) intoxication.
      OBJECTIVE: The present study evaluates the protective effect of PLo against
      sodium arsenite-induced hepatic dysfunction and oxidative stress in experimental
      Wistar rats. MATERIALS AND METHODS: Twenty-eight rats were equally divided into
      four groups; the first served as a control, the remaining groups were
      respectively treated with PLo (3.3 mL/kg body weight), sodium arsenite (5.55
      mg/kg body weight) and a combination of sodium arsenite and PLo. After 21
      consecutive days, cellular functions were evaluated by hematological, biochemical
      and oxidative stress markers. RESULTS: A significant decrease in the levels of
      red blood cells, haemoglobin (p <= 0.001), hematocrit (p <= 0.001), reduced
      glutathione and metallothionein (p <= 0.05) associated with a significant
      increase of malondialdehyde (p <= 0.001) were noticed in the arsenic-exposed
      group when compared to the control. The As-treated group also exhibited an
      increase in hepatic antioxidant enzymes namely superoxide dismutase, glutathione
      peroxidase (p <= 0.01) and catalase (p <= 0.05). However, the co-administration
      of PLo has relatively reduced arsenic effect. CONCLUSION: The results showed that
      arsenic intoxication disturbed the liver pro-oxidant/antioxidant status. PLo co
      administration mitigates arsenic-induced oxidative damage in rat.

PMID- 25946017
TI  - Genomic analysis reveals the molecular basis for capsule loss in the group B
      Streptococcus population.
AB  - The human and bovine bacterial pathogen Streptococcus agalactiae (Group B
      Streptococcus, GBS) expresses a thick polysaccharide capsule that constitutes a
      major virulence factor and vaccine target. GBS can be classified into ten
      distinct serotypes differing in the chemical composition of their capsular
      polysaccharide. However, non-typeable strains that do not react with anti
      capsular sera are frequently isolated from colonized and infected humans and
      cattle. To gain a comprehensive insight into the molecular basis for the loss of
      capsule expression in GBS, a collection of well-characterized non-typeable
      strains was investigated by genome sequencing. Genome based phylogenetic analysis
      extended to a wide population of sequenced strains confirmed the recently
      observed high clonality among GBS lineages mainly containing human strains, and
      revealed a much higher degree of diversity in the bovine population. Remarkably,
      non-typeable strains were equally distributed in all lineages. A number of
      distinct mutations in the cps operon were identified that were apparently
      responsible for inactivation of capsule synthesis. The most frequent genetic
      alterations were point mutations leading to stop codons in the cps genes, and the
      main target was found to be cpsE encoding the portal glycosyl transferase of
      capsule biosynthesis. Complementation of strains carrying missense mutations in
      cpsE with a wild-type gene restored capsule expression allowing the
      identification of amino acid residues essential for enzyme activity.

PMID- 25946018
TI  - Brucella abortus Induces the Premature Death of Human Neutrophils through the
      Action of Its Lipopolysaccharide.
AB  - Most bacterial infections induce the activation of polymorphonuclear neutrophils
      (PMNs), enhance their microbicidal function, and promote the survival of these
      leukocytes for protracted periods of time. Brucella abortus is a stealthy
      pathogen that evades innate immunity, barely activates PMNs, and resists the
      killing mechanisms of these phagocytes. Intriguing clinical signs observed during
      brucellosis are the low numbers of Brucella infected PMNs in the target organs
      and neutropenia in a proportion of the patients; features that deserve further
      attention. Here we demonstrate that B. abortus prematurely kills human PMNs in a
      dose-dependent and cell-specific manner. Death of PMNs is concomitant with the
      intracellular Brucella lipopolysaccharide (Br-LPS) release within vacuoles. This
      molecule and its lipid A reproduce the premature cell death of PMNs, a phenomenon
      associated to the low production of proinflammatory cytokines. Blocking of CD14
      but not TLR4 prevents the Br-LPS-induced cell death. The PMNs cell death departs
      from necrosis, NETosis and classical apoptosis. The mechanism of PMN cell death
      is linked to the activation of NADPH-oxidase and a modest but steadily increase
      of ROS mediators. These effectors generate DNA damage, recruitments of check
      point kinase 1, caspases 5 and to minor extent of caspase 4, RIP1 and Ca++
      release. The production of IL-1beta by PMNs was barely stimulated by B. abortus
      infection or Br-LPS treatment. Likewise, inhibition of caspase 1 did not hamper
      the Br-LPS induced PMN cell death, suggesting that the inflammasome pathway was
      not involved. Although activation of caspases 8 and 9 was observed, they did not
      seem to participate in the initial triggering mechanisms, since inhibition of
      these caspases scarcely blocked PMN cell death. These findings suggest a
      mechanism for neutropenia in chronic brucellosis and reveal a novel Brucella-host
      cross-talk through which B. abortus is able to hinder the innate function of PMN.

PMID- 25946020
TI  - Chinese Social Media Reaction to Information about 42 Notifiable Infectious
      Diseases.
AB  - This study aimed to identify what information triggered social media users'
      responses regarding infectious diseases. Chinese microblogs in 2012 regarding 42
      infectious diseases were obtained through a keyword search in the Weiboscope
      database. Qualitative content analysis was performed for the posts pertinent to
      each keyword of the day of the year with the highest daily count. Similar posts
      were grouped and coded. We identified five categories of information that
      increased microblog traffic pertaining to infectious diseases: news of an
      outbreak or a case; health education/information; alternative health
      information/Traditional Chinese Medicine; commercial advertisement/entertainment;
      and social issues. News unrelated to the specified infectious diseases also led
      to elevated microblog traffic. Our study showcases the diverse contexts from
      which increased social media traffic occur. Our results will facilitate better
      health communication as causes underlying increased social media traffic are
      revealed.

PMID- 25946019
TI  - Variation in Type 2 Diabetes-Related Phenotypes among Apolipoprotein E-Deficient
      Mouse Strains.
AB  - We recently have found that apolipoprotein E-deficient (Apoe(-/-)) mice with the
      C57BL/6 background develop type 2 diabetes when fed a Western diet for 12 weeks.
      In the present study we constructed multiple Apoe(-/-) mouse strains to find
      diabetes-related phenotyptic variations that might be linked to atherosclerosis
      development. Evaluation of both early and advanced lesion formation in aortic
      root revealed that C57BL/6, SWR/J, and SM/J Apoe(-/-) mice were susceptible to
      atherosclerosis and that C3H/HeJ and BALB/cJ Apoe(-/-) mice were relatively
      resistant. On a chow diet, fasting plasma glucose varied among strains with
      C3H/HeJ having the highest (171.1 +/- 9.7 mg/dl) and BALB/cJ the lowest level
      (104.0 +/- 6.6 mg/dl). On a Western diet, fasting plasma glucose rose
      significantly in all strains, with C57BL/6, C3H/HeJ and SWR/J exceeding 250
      mg/dl. BALB/cJ and C3H/HeJ were more tolerant to glucose loading than the other 3
      strains. C57BL/6 was sensitive to insulin while other strains were not. Non
      fasting blood glucose was significantly lower in C3H/HeJ and BALB/cJ than
      C57BL/6, SM/J, and SWR/J. Glucose loading induced the 1st and the 2nd phase of
      insulin secretion in BALB/cJ, but the 2nd phase was not observed in other
      strains. Morphological analysis showed that BALB/cJ had the largest islet area
      (1,421,493 +/- 61,244 MUm(2)) and C57BL/6 had the smallest one (747,635 +/-
      41,798 MUm(2)). This study has demonstrated strain-specific variations in the
      metabolic and atherosclerotic phenotypes, thus laying the basis for future
      genetic characterization.

PMID- 25946021
TI  - Th1-Like ICOS+ Foxp3+ Treg Cells Preferentially Express CXCR3 and Home to beta
      Islets during Pre-Diabetes in BDC2.5 NOD Mice.
AB  - Type 1 diabetes (T1D) occurs through a breakdown of self-tolerance resulting in
      the autoimmune destruction of the insulin producing beta-islets of the pancreas.
      A numerical and functional waning of CD4+ Foxp3+ regulatory T (Treg) cells,
      prompted by a pancreatic IL-2 deficiency, accompanies Th1 autoimmunity and T1D
      progression in non-obese diabetic (NOD) mice. Recently, we identified a dominant
      subset of intra-islet Treg cells that expresses the ICOS costimulatory receptor
      and promotes self-tolerance delaying the onset of T1D. ICOS co-stimulation
      potently enhances IL-2 induced survival and proliferation, and suppressive
      activity of Treg cells in situ. Here, we propose an ICOS-dependent mechanism of
      Treg cell homing to the beta-islets during pre-diabetes in the NOD model via
      upregulation of the CXCR3 chemokine receptor. The islet-specific ICOS+ Treg cell
      subset preferentially expresses CXCR3 in the pancreatic lymph nodes (pLN) in
      response to Teff cell-mediated pancreatic inflammation, an expression correlating
      with the onset and magnitude of IFN-gamma production by Teff cells in pancreatic
      sites. We also reveal that intra-pancreatic APC populations and insulin-producing
      beta, but not alpha nor delta, islet cells secrete the CXCR3 chemokines, CXCL9,
      10 and 11, and selectively promote ICOS+ CXCR3+ Treg cell chemotaxis in vitro.
      Strikingly, islet-derived Treg cells also produce these chemokines suggesting an
      auto-regulation of homing by this subset. Unlike ICOS- cells, ICOS+ Treg cells
      adopt a Th1-like Treg phenotype while maintaining their suppressive capacity,
      characterized by expression of T-bet and CXCR3 and production of IFN-gamma in the
      draining pLNs. Finally, in vivo neutralization of IFN-gamma blocked Treg cell
      CXCR3 upregulation evincing its role in regulating expression of this chemokine
      receptor by Treg cells. Thus, CXCR3-mediated trafficking of Treg cells could
      represent a mechanism of homeostatic immunoregulation during diabetogeneesis.

PMID- 25946022
TI  - Home Versus Away Competition: Effect on Psychophysiological Variables in Elite
      Rugby Union.
AB  - This study evaluated the effect of game venue and starting status on
      precompetitive psychophysiological measures in elite rugby union. Saliva samples
      were taken from players (starting XV, n = 15, and nonstarters, n = 9) on a
      control day and 90 min before 4 games played consecutively at home and away
      venues against local rivals and league leaders. Precompetition psychological
      states were assessed using the Competitive State Anxiety Inventory-2. The squad
      recorded 2 wins (home) and 2 losses (away) over the study period. Calculated
      effect sizes (ESs) showed higher pregame cortisol- (C) and testosterone- (T)
      difference values before all games than on a baseline control day (ES 0.7-1.5).
      Similar findings were observed for cognitive and somatic anxiety. Small between
      venues C differences were observed in starting XV players (ES 0.2-0.25).
      Conversely, lower home T- (ES 0.95) and higher away C- (ES 0.6) difference values
      were observed in nonstarters. Lower T-difference values were apparent in
      nonstarters (vs starting XV) before home games, providing evidence of a between
      groups effect (ES 0.92). Findings show an anticipatory rise in
      psychophysiological variables before competition. Knowledge of starting status
      appears a moderating factor in the magnitude of player endocrine response between
      home and away games. 

PMID- 25946023
TI  - Letter: IgG4-hepatopathy and IgG4-associated autoimmune hepatitis--authors'
      reply.

PMID- 25946024
TI  - Versatile, Reversible, and Reusable Gel of a Monocholesteryl Conjugated
      Calix[4]arene as Functional Material to Store and Release Dyes and Drugs
      Including Doxorubicin, Curcumin, and Tocopherol.
AB  - Gels are interesting soft materials owing to their functional properties leading
      to potential applications. This paper deals with the synthesis of monocholesteryl
      derivatized calix[4]arene (G) and its instantaneous gelation at a minimum gelator
      concentration of 0.6% in 1:1 v/v THF/acetonitrile. The gel shows remarkable
      thermoreversibility by exhibiting Tgel->sol at ~48  degrees C and is demonstrated
      for several cycles. The gel shows an organized network of nanobundles, while that
      of the sol shows spherical nanoaggregates in microscopy. A bundle with ~12 nm
      diameter possessing hydrophobic pockets in itself is obtained from
      computationally modeled gel, and hence the gel is suitable for storage and
      release applications. The guest-entrapped gels exhibit the same microstructures
      as that observed with simple gels, while fluorescence spectra and molecular
      mechanics suggests that the drug molecules occupy the hydrophobic pockets. All
      the entrapped drug molecules are released into water, suggesting a complete
      recovery of the trapped species. The reusability of the gel for the storage and
      release of the drug into water is demonstrated for four consecutive cycles, and
      hence the gel formed from G acts as a functional material that finds application
      in drug delivery. 

PMID- 25946025
TI  - Sensitivity of quantitative myocardial dynamic contrast-enhanced MRI to
      saturation pulse efficiency, noise and t1 measurement error: Comparison of
      nonlinearity correction methods.
AB  - PURPOSE: To compare methods designed to minimize or correct signal nonlinearity
      in quantitative myocardial dynamic contrast-enhanced (DCE) MRI. METHODS: DCE-MRI
      studies were simulated and data acquired in eight volunteers. Signal nonlinearity
      was corrected using either a dual-bolus approach or model-based correction using
      proton-density weighted imaging (conventional or dual-sequence acquisition) or T1
      data (native or bookend). Scanning of healthy and infarcted myocardium at 3 T was
      simulated, including noise, saturation imperfection and T1 measurement error.
      Data were analyzed using model-based deconvolution with a one-compartment (mono
      exponential) model. RESULTS: Substantial variation between methods was
      demonstrated in volunteers. In simulations the dual-bolus method proved stable
      for realistic levels of saturation efficiency but demonstrated bias due to
      residual nonlinearity. Model-based methods performed ideally in the absence of
      confounding error sources and were generally robust to noise or saturation
      imperfection, except for native T1 based correction which was highly sensitive to
      the latter. All methods demonstrated large variation in accuracy above an over
      saturation level where baseline signal was nulled. For the dual-sequence approach
      this caused substantial bias at the saturation efficiencies observed in
      volunteers. CONCLUSION: The choice of nonlinearity correction method in
      myocardial DCE-MRI impacts on accuracy and precision of estimated parameters,
      particularly in the presence of nonideal saturation.

PMID- 25946026
TI  - Intestinal alkaline phosphatase inhibits the translocation of bacteria of gut
      origin in mice with peritonitis: mechanism of action.
AB  - Exogenous intestinal alkaline phosphatase (IAP), an enzyme produced endogenously
      at the brush edge of the intestinal mucosa, may mitigate the increase in aberrant
      intestinal permeability increased during sepsis. The aim of this study was to
      test the efficacy of the inhibitory effect of IAP on acute intestinal
      inflammation and to study the molecular mechanisms underlying IAP in ameliorating
      intestinal permeability. We used an in vivo imaging method to evaluate disease
      status and the curative effect of IAP. Two Escherichia coli (E.coli) B21 strains,
      carrying EGFP labeled enhanced green fluorescent protein (EGFP) and RFP labeled
      red fluorescent protein (RFP), were constructed as tracer bacteria and were
      administered orally to C57/B6N mice to generate an injection peritonitis (IP)
      model. The IP model was established by injecting inflammatory lavage fluid.
      C57/B6N mice bearing the tracer bacteria were subsequently treated with (IP+IAP
      group), or without IAP (IP group). IAP was administered to the mice via tail vein
      injections. The amount of tracer bacteria in the blood, liver, and lungs at 24 h
      post-injection was analyzed via flow cytometry (FCM), in vivo imaging, and
      Western blotting. Intestinal barrier function was measured using a flux assay
      with the macro-molecule fluorescein isothiocyanate dextran, molecular weight
      40kD, (FD40). To elucidate the molecular mechanism underlying the effects of IAP,
      we examined the levels of ERK phosphorylation, and the expression levels of
      proteins in the ERK-SP1-VEGF and ERK-Cdx-2-Claudin-2 pathways. We observed that
      IAP inhibited the expression of Claudin-2, a type of cation channel-forming
      protein, and VEGF, a cytokine that may increase intestinal permeability by
      reducing the levels of dephosphorylated ERK. In conclusion, exogenous IAP shows a
      therapeutic effect in an injection peritonitis model. This including inhibition
      of bacterial translocation. Moreover, we have established an imaging methodology
      for live-animals can effectively evaluate intestinal permeability and aberrant
      bacterial translocation in IP models. 

PMID- 25946027
TI  - Induced pluripotent stem cell derived macrophages as a cellular system to study
      salmonella and other pathogens.
AB  - A number of pathogens, including several human-restricted organisms, persist and
      replicate within macrophages (Mphis) as a key step in pathogenesis. The
      mechanisms underpinning such host-restricted intracellular adaptations are poorly
      understood, in part, due to a lack of appropriate model systems. Here we explore
      the potential of human induced pluripotent stem cell derived macrophages (iPSDMs)
      to study such pathogen interactions. We show iPSDMs express a panel of
      established Mphi-specific markers, produce cytokines, and polarise into classical
      and alternative activation states in response to IFN-gamma and IL-4 stimulation,
      respectively. iPSDMs also efficiently phagocytosed inactivated bacterial
      particles as well as live Salmonella Typhi and S. Typhimurium and were able to
      kill these pathogens. We conclude that iPSDMs can support productive Salmonella
      infection and propose this as a flexible system to study host/pathogen
      interactions. Furthermore, iPSDMs can provide a flexible and practical cellular
      platform for assessing host responses in multiple genetic backgrounds. 

PMID- 25946028
TI  - The Influence of Immunization Route, Tissue Microenvironment, and Cytokine Cell
      Milieu on HIV-Specific CD8+ T Cells Measured Using Fluidigm Dynamic Arrays.
AB  - Thirty different genes including cytokines, chemokines, granzymes, perforin and
      specifically integrins were evaluated in Peyer's patch-KdGag197-205-specific CD8+
      T cells (pools of 100 cells) using Fluidigm 48.48 Dynamic arrays following three
      different prime-boost immunization strategies. Data revealed that the route of
      prime or the booster immunization differentially influenced the integrin
      expression profile on gut KdGag197-205-specific CD8+ T cells. Specifically,
      elevated numbers of integrin alphaE and alphaD expressing gut KdGag197-205
      specific CD8+ T cells were detected following mucosal but not systemic priming.
      Also, alphaE/beta7 and alphaD/beta2 heterodimerization were more noticeable in an
      intranasal (i.n.)/i.n. vaccination setting compared to i.n./intramuscular (i.m)
      or i.m./i.m. vaccinations. Moreover, in all vaccine groups tested alpha4 appeared
      to heterodimerize more closely with beta7 then beta1. Also MIP-1beta, RANTES,
      CCR5, perforin and integrin alpha4 bio-markers were significantly elevated in
      i.n./i.m. and i.m./i.m. immunization groups compared to purely mucosal i.n./i.n.
      delivery. Furthermore, when wild type (WT) BALB/c and IL-13 knockout (KO) mice
      were immunized using i.n./i.m. strategy, MIP-1alpha, MIP-1beta, RANTES, integrins
      alpha4, beta1 and beta7 mRNA expression levels were found to be significantly
      different, in mucosal verses systemic KdGag197-205-specific CD8+ T cells.
      Interestingly, the numbers of gut KdGag197-205-specific CD8+ T cells expressing
      gut-homing markers alpha4beta7 and CCR9 protein were also significantly elevated
      in IL-13 KO compared to WT control. Collectively, our findings further
      corroborate that the route of vaccine delivery, tissue microenvironment and IL-13
      depleted cytokine milieu can significantly alter the antigen-specific CD8+ T cell
      gene expression profiles and in turn modulate their functional avidities as well
      as homing capabilities. 

PMID- 25946029
TI  - Human HtrA4 Expression Is Restricted to the Placenta, Is Significantly Up
      Regulated in Early-Onset Preeclampsia, and High Levels of HtrA4 Cause Endothelial
      Dysfunction.
AB  - CONTEXT: Preeclampsia (PE), a pregnancy-specific disorder closely associated with
      endothelial dysfunction and capillary leakage, is responsible for substantial
      maternal/fetal morbidity and mortality. PE can be classified as early-onset (<34
      wk) and late-onset (>34 wk); the two subsets differ in presentation and
      pathogenesis. OBJECTIVES: The objectives of the study were to examine serine
      protease high-temperature requirement factor A4 (HtrA4) expression in the
      placenta and other human tissues and in early-onset vs late-onset PE, to
      determine serum HtrA4 levels in normal pregnancy and in PE subtypes, and to
      investigate the effect of high levels of HtrA4 on endothelial integrity and
      function. METHODS: Microarray data analysis and RT-PCR determined HtrA4
      expression in the human placenta, various tissues, and cell lines. The serum
      HtrA4 protein levels were analyzed by an ELISA. The potential impact of excessive
      circulating HtrA4 on the maternal vasculature was determined by in vitro
      endothelial tube and permeability assays. RESULTS: Human HtrA4 expression was
      restricted to the placenta and significantly up-regulated in early-onset but not
      late-onset PE. The serum HtrA4 levels in normal pregnancy increased significantly
      between the first and second trimesters and then remained constant. Women with
      early-onset but not late-onset PE showed significantly higher HtrA4 levels in
      serum compared with gestational age-matched controls. In cell models, high levels
      of HtrA4 disturbed endothelial cell tube formation and permeability in a dose
      dependent manner, and this was linked to alterations in junctional proteins and
      microtubule organization. CONCLUSIONS: HtrA4 represents a novel placenta-specific
      serine protease that is altered specifically in early-onset PE with potential
      causal roles in endothelial dysfunction and disease development.

PMID- 25946030
TI  - Excess Mortality in Women and Young Adults With Nonfunctioning Pituitary Adenoma:
      A Swedish Nationwide Study.
AB  - CONTEXT: Patients with hypopituitarism of various etiologies have excess
      mortality. The mortality in patients with nonfunctioning pituitary adenoma
      (NFPA), regardless of pituitary function, is less well studied. OBJECTIVE: Our
      aim was to investigate mortality in patients with NFPA and to examine whether age
      at diagnosis, gender, tumor treatments, or hormonal deficiencies influence the
      outcome. DESIGN: NFPA patients were identified and followed up in nationwide
      health registries in Sweden, 1987-2011. The criteria for identification were
      tested and validated in a subpopulation of the patients. SETTINGS: This was a
      nationwide, population-based study. PATIENTS: A total of 2795 unique patients
      with NFPA (1502 men, 1293 women) were identified and included in the study. Mean
      age at diagnosis was 58 years (men, 60 y; women, 56 y) and mean follow-up time
      was 7 years (range 0-25 y). INTERVENTION: There were no interventions. MAIN
      OUTCOME MEASURES: Standardized mortality ratios (SMRs) and annual incidence rates
      were calculated using the Swedish population as reference and presented with 95%
      confidence intervals. RESULTS: Annual incidence of NFPA was 20.3 (18.8-21.9)
      cases per 1 million inhabitants. During the observation period, 473 patients died
      against an expected 431, resulting in an SMR of 1.10 (1.00-1.20). Patients
      diagnosed at younger than 40 years of age had an increased SMR of 2.68 (1.23
      5.09). The SMR for patients with hypopituitarism (n = 1500) was 1.06 (0.94-1.19),
      and for patients with diabetes insipidus (n = 145), it was 1.71 (1.07-2.58). The
      SMR was increased in women with NFPA (1.29; 1.11-1.48) but not in men (1.00; 0.88
      1.12). Women, but not men, with a diagnosis of hypopituitarism and/or diabetes
      insipidus also had an increased mortality ratio. SMRs due to cerebrovascular
      (1.73; 1.34-2.19) and infectious diseases (2.08; 1.17-3.44) were increased,
      whereas the SMR for malignant tumors was decreased (0.76; 0.61-0.94).
      CONCLUSIONS: This nationwide study of patients with NFPA showed an overall excess
      mortality in women and in patients with a young age at diagnosis. Increased
      mortality was seen for cerebrovascular and infectious diseases.

PMID- 25946031
TI  - Therapeutic Effectiveness of Screening for Multiple Endocrine Neoplasia Type 2A.
AB  - CONTEXT: Although technological progress revolutionized detection of genetic
      predisposition to medullary thyroid cancer (MTC), carriers of mutations of
      disparate risks may not have benefitted alike from screening. OBJECTIVE: This
      investigation aimed at assessing the achievements of screening for multiple
      endocrine neoplasia type 2A (MEN 2A) in Germany and identifying current
      challenges. DESIGN: This was a retrospective analysis comprising 455 carriers at
      risk of MEN 2A screened and operated between 1963 and 2014. SETTING: The setting
      was tertiary surgical referral centers. PATIENTS: Included were 175 carriers of
      American Thyroid Association (ATA) level C mutations (codon 634); 116 carriers of
      ATA level B mutations (codons 609, 611, 618, 620 and 630); and 164 carriers of
      ATA level A mutations (codons 768, 790, 791, 804 and 891). INTERVENTIONS: The
      intervention was thyroidectomy. MAIN OUTCOME MEASURES: Main outcome measures were
      percentage of index patients among all carriers and percentage of MTC, node
      positive MTC, and biochemical cure among non-index patients. RESULTS: The
      percentage of index patients among all carriers fell from 50% (ATA level C) and
      100% (ATA levels B and A) to 16, 29, and 31%, respectively. Among non-index
      patients, the percentage of MTC fell for ATA levels C and B but not for ATA level
      A mutations. The corresponding percentage of node-positive MTC declined since
      1963 from 100 to 0% (ATA level C) and since 1995 from 67 to 33% (ATA level B) and
      from 11 to 10% (ATA level A), whereas biochemical cure increased from 0 to 100%
      since 1963 (ATA level C), and since 1995 from 71 to 78% (ATA level B) and from 95
      to 100% (ATA level A). CONCLUSIONS: Screening efforts need to focus on sporadic
      appearing MTC to deplete the pool of unrecognized carriers of ATA level B and A
      mutations and enable earlier pre-emptive thyroidectomy in their offspring.

PMID- 25946032
TI  - Are protected areas required to maintain functional diversity in human-modified
      landscapes?
AB  - The conversion of forest to agriculture across the world's tropics, and the
      limited space for protected areas, has increased the need to identify effective
      conservation strategies in human-modified landscapes. Isolated trees are believed
      to conserve elements of ecological structure, providing micro-sites for
      conservation in matrix landscapes, and facilitating seed dispersal and forest
      restoration. Here we investigate the role of isolated Ficus trees, which are of
      critical importance to tropical forest ecosystems, in conserving frugivore
      composition and function in a human-modified landscape in Assam, India. We
      surveyed the frugivorous birds feeding at 122 isolated Ficus trees, 33 fruit
      trees, and 31 other large trees across a range of 32 km from the nearest intact
      forest. We found that Ficus trees attracted richer and more abundant assemblages
      of frugivores than the other tree categories. However, incidence function
      estimates revealed that forest specialist species decreased dramatically within
      the first kilometre of the forest edge. Despite this, species richness and
      functional diversity remained consistent across the human-modified landscape, as
      habitat generalists replaced forest-dependent frugivores, and accounted for most
      of the ecological function found in Ficus trees near the forest edge. We
      recommend that isolated Ficus trees are awarded greater conservation status, and
      suggest that their conservation can support ecologically functional networks of
      frugivorous bird communities. 

PMID- 25946035
TI  - Human Basal Tear Peptidome Characterization by CID, HCD, and ETD Followed by in
      Silico and in Vitro Analyses for Antimicrobial Peptide Identification.
AB  - Endogenous peptides are valuable targets in the analysis of biological processes.
      The tear film contains proteins and peptides released by the tear duct mucosal
      cells, including antimicrobial peptides involved in the protection against
      exogenous pathogens; however, the peptide content of the tear liquid remains
      poorly characterized. We analyzed naturally occurring peptides isolated from
      human basal tears. Mass spectrometry analysis of endogenous peptides presents a
      number of drawbacks, including size heterogeneity and nonpredictable
      fragmentation patterns, among others. Therefore, CID, ETD, and HCD methods were
      used for the characterization of the tear peptide content. The contribution of
      DMSO as an additive of the chromatographic solvents was also evaluated. We
      identified 157, 131, and 122 peptides using CID-, ETD-, and HCD-based methods,
      respectively. Altogether, 234 different peptides were identified, leading to the
      generation of the biggest data set of endogenous tear peptides to date. The
      antimicrobial activity prediction analysis performed in silico revealed different
      putative antimicrobial peptides. Two of the extracellular glycoprotein lacritin
      peptides were de novo synthesized, and their antimicrobial activity was confirmed
      in vitro. Our findings demonstrate the benefits of using different fragmentation
      methods for the analysis of endogenous peptides and provide a useful approach for
      the discovery of peptides with antimicrobial activity. 

PMID- 25946033
TI  - Immunomodulatory Protein from Ganoderma microsporum Induces Pro-Death Autophagy
      through Akt-mTOR-p70S6K Pathway Inhibition in Multidrug Resistant Lung Cancer
      Cells.
AB  - Chemoresistance in cancer therapy is an unfavorable prognostic factor in non
      small cell lung cancer (NSCLC). Elevation of intracellular calcium level in
      multidrug resistant (MDR) sublines leads to sensitization of MDR sublines to cell
      death. We demonstrated that a fungal protein from Ganoderma microsporum, GMI,
      elevates the intracellular calcium level and reduces the growth of MDR subline
      via autophagy and apoptosis, regardless of p-glycoprotein (P-gp) overexpression,
      in mice xenograft tumors. In addition, we examined the roles of autophagy in the
      death of MDR A549 lung cancer sublines by GMI, thapsigargin (TG) and tunicamycin
      (TM) in vitro. Cytotoxicity of TG was inhibited by overexpressed P-gp. However,
      TM-induced death of MDR sublines was independent of P-gp level. Combinations of
      TG and TM with either docetaxel or vincristine showed no additional cytotoxic
      effects on MDR sublines. TG- and TM-mediated apoptosis of MDR sublines was
      demonstrated on Annexin-V assay and Western blot and repressed by pan-caspase
      inhibitor (Z-VAD-FMK). Treatment of MDR sublines with TG and TM also augmented
      autophagy with accumulation of LC3-II proteins, breakdown of p62 and formation of
      acidic vesicular organelles (AVOs). Inhibition of ATG5 by shRNA silencing
      significantly reduced autophagy and cell death but not apoptosis following TG or
      TM treatment. GMI treatment inhibited the phosphorylation of Akt/S473 and
      p70S6K/T389. Interestingly, the phosphorylation of ERK was not associated with
      GMI-induced autophagy. We conclude that autophagy plays a pro-death role in
      acquired MDR and upregulation of autophagy by GMI via Akt/mTOR inhibition
      provides a potential strategy for overcoming MDR in the treatment of lung
      cancers. 

PMID- 25946036
TI  - Surface charge determines the lung inflammogenicity: A study with polystyrene
      nanoparticles.
AB  - Surface functionalization is a routine process to improve the behavior of
      nanoparticles (NPs), but the induced surface properties, such as surface charge,
      can produce differential toxicity profiles. Here, we synthesized a library of
      covalently functionalized fluorescent polymeric NPs (F-PLNPs) to evaluate the
      role of surface charge on the acute inflammation and the localization in the
      lung. Guanidinium-, acetylated-, zwitterionic-, hydroxylated-, PEGylated-,
      carboxylated- and sulfated-F-PLNPs were synthesized from aminated-F-PLNP. The
      primary particle sizes were identical, but the hydrodynamic sizes ranged from 210
      to 345 nm. Following surface functionalization, the F-PLNPs showed diverse zeta
      potentials from -41.2 to 31.0 mV, and each F-PLNP showed a single, narrow peak.
      Pharyngeal aspiration with these eight types of F-PLNPs into rats produced
      diverse acute lung inflammation, with zeta potentials of the F-PLNPs showing
      excellent correlation with acute pulmonary inflammation parameters including the
      percentage of polymorphonuclear leukocytes (R(2) = 0.90, p < 0.0001) and the
      levels of interleukin-1beta (R(2) = 0.83, p < 0.0001) and of cytokine-induced
      neutrophil chemoattractant-3 (R(2) = 0.86, p < 0.0001). These results imply that
      surface charge is a key factor influencing lung inflammation by functionalized
      polymeric NPs, which further confirms and extends the surface charge paradigm
      that we reported for pristine metal oxide NPs. This demonstrates that the surface
      charge paradigm is a valuable tool to predict the toxicity of NPs. 

PMID- 25946034
TI  - Duplicated leptin receptors in two species of eel bring new insights into the
      evolution of the leptin system in vertebrates.
AB  - Since its discovery in mammals as a key-hormone in reproduction and metabolism,
      leptin has been identified in an increasing number of tetrapods and teleosts.
      Tetrapods possess only one leptin gene, while most teleosts possess two leptin
      genes, as a result of the teleost third whole genome duplication event (3R).
      Leptin acts through a specific receptor (LEPR). In the European and Japanese
      eels, we identified two leptin genes, and for the first time in vertebrates, two
      LEPR genes. Synteny analyses indicated that eel LEPRa and LEPRb result from
      teleost 3R. LEPRb seems to have been lost in the teleost lineage shortly after
      the elopomorph divergence. Quantitative PCRs revealed a wide distribution of
      leptins and LEPRs in the European eel, including tissues involved in metabolism
      and reproduction. Noticeably, leptin1 was expressed in fat tissue, while leptin2
      in the liver, reflecting subfunctionalization. Four-month fasting had no impact
      on the expression of leptins and LEPRs in control European eels. This might be
      related to the remarkable adaptation of silver eel metabolism to long-term
      fasting throughout the reproductive oceanic migration. In contrast, sexual
      maturation induced differential increases in the expression of leptins and LEPRs
      in the BPG-liver axis. Leptin2 was strikingly upregulated in the liver, the
      central organ of the reproductive metabolic challenge in teleosts. LEPRs were
      differentially regulated during sexual maturation, which may have contributed to
      the conservation of the duplicated LEPRs in this species. This suggests an
      ancient and positive role of the leptin system in the vertebrate reproductive
      function. This study brings new insights on the evolutionary history of the
      leptin system in vertebrates. Among extant vertebrates, the eel represents a
      unique case of duplicated leptins and leptin receptors as a result of 3R. 

PMID- 25946038
TI  - Effects of short-term training and detraining on VO2 kinetics: Faster VO2
      kinetics response after one training session.
AB  - This study examined the time course of short-term training and detraining-induced
      changes in oxygen uptake ( V  O 2 ) kinetics. Twelve men (24 +/- 3 years) were
      assigned to either a 50% or a 70% of V  O 2 m a x training intensity (n = 6 per
      group). V  O 2 was measured breath-by-breath. Changes in deoxygenated-hemoglobin
      concentration (Delta[HHb]) were measured by near-infrared spectroscopy. Moderate
      intensity exercise on-transient V  O 2 and Delta[HHb] were modeled with a mono
      exponential and normalized (0-100% of response) and the [ H H b ] / V  O 2 ratio
      was calculated. Similar changes in time constant of V  O 2 ( t V  O 2 ) were
      observed in both groups. The combined group mean for t V  O 2 decreased ~14%
      (32.3 to 27.9 s, P < 0.05) after one training session with a further ~11%
      decrease (27.9 to 24.8 s, P < 0.05) following two training sessions. The t V  O 2
      p remained unchanged throughout the remaining of training and detraining. A
      significant "overshoot" in the [ H H b ] / V  O 2 ratio was decreased (albeit not
      significant) after one training session, and abolished (P < 0.05) after the
      second one, with no overshoot observed thereafter. Speeding of V  O 2 kinetics
      was remarkably quick with no further changes being observed with continuous
      training or during detraining. Improve matching of local O2 delivery to O2
      utilization is a mechanism proposed to influence this response. 

PMID- 25946037
TI  - Discovery of a Small Non-AUG-Initiated ORF in Poleroviruses and Luteoviruses That
      Is Required for Long-Distance Movement.
AB  - Viruses in the family Luteoviridae have positive-sense RNA genomes of around 5.2
      to 6.3 kb, and they are limited to the phloem in infected plants. The Luteovirus
      and Polerovirus genera include all but one virus in the Luteoviridae. They share
      a common gene block, which encodes the coat protein (ORF3), a movement protein
      (ORF4), and a carboxy-terminal extension to the coat protein (ORF5). These three
      proteins all have been reported to participate in the phloem-specific movement of
      the virus in plants. All three are translated from one subgenomic RNA, sgRNA1.
      Here, we report the discovery of a novel short ORF, termed ORF3a, encoded near
      the 5' end of sgRNA1. Initially, this ORF was predicted by statistical analysis
      of sequence variation in large sets of aligned viral sequences. ORF3a is
      positioned upstream of ORF3 and its translation initiates at a non-AUG codon.
      Functional analysis of the ORF3a protein, P3a, was conducted with Turnip yellows
      virus (TuYV), a polerovirus, for which translation of ORF3a begins at an ACG
      codon. ORF3a was translated from a transcript corresponding to sgRNA1 in vitro,
      and immunodetection assays confirmed expression of P3a in infected protoplasts
      and in agroinoculated plants. Mutations that prevent expression of P3a, or which
      overexpress P3a, did not affect TuYV replication in protoplasts or inoculated
      Arabidopsis thaliana leaves, but prevented virus systemic infection (long
      distance movement) in plants. Expression of P3a from a separate viral or plasmid
      vector complemented movement of a TuYV mutant lacking ORF3a. Subcellular
      localization studies with fluorescent protein fusions revealed that P3a is
      targeted to the Golgi apparatus and plasmodesmata, supporting an essential role
      for P3a in viral movement. 

PMID- 25946039
TI  - (6E,10E) Isopolycerasoidol and (6E,10E) Isopolycerasoidol Methyl Ester,
      Prenylated Benzopyran Derivatives from Pseuduvaria monticola Induce Mitochondrial
      Mediated Apoptosis in Human Breast Adenocarcinoma Cells.
AB  - Phytochemicals from Pseuduvaria species have been reported to display a wide
      range of biological activities. In the present study, a known benzopyran
      derivative, (6E,10E) isopolycerasoidol (1), and a new benzopyran derivative,
      (6E,10E) isopolycerasoidol methyl ester (2), were isolated from a methanol
      extract of Pseuduvaria monticola leaves. The structures of the isolated compounds
      were elucidated by spectroscopic methods including 1D and 2D NMR, IR, UV, and
      LCMS-QTOF, and by comparison with previously published data. The anti
      proliferative and cytotoxic effects of these compounds on human breast cancer
      cell-lines (MCF-7 and MDA-MB-231) and a human normal breast epithelial cell line
      (MCF-10A) were investigated. MTT results revealed both (1) and (2) were efficient
      in reducing cell viability of breast cancer cells. Flow cytometry analysis
      demonstrated that (1) and (2) induced cell death via apoptosis, as demonstrated
      by an increase in phosphotidylserine exposure. Both compounds elevated ROS
      production, leading to reduced mitochondrial membrane potential and increased
      plasma membrane permeability in breast cancer cells. These effects occurred
      concomitantly with a dose-dependent activation of caspase 3/7 and 9, a down
      regulation of the anti-apoptotic gene BCL2 and the accumulation of p38 MAPK in
      the nucleus. Taken together, our data demonstrate that (1) and (2) induce
      intrinsic mitochondrial-mediated apoptosis in human breast cancer cells, which
      provides the first pharmacological evidence for their future development as
      anticancer agents. 

PMID- 25946040
TI  - L-arginine destabilizes oral multi-species biofilm communities developed in human
      saliva.
AB  - The amino acid L-arginine inhibits bacterial coaggregation, is involved in cell
      cell signaling, and alters bacterial metabolism in a broad range of species
      present in the human oral cavity. Given the range of effects of L-arginine on
      bacteria, we hypothesized that L-arginine might alter multi-species oral biofilm
      development and cause developed multi-species biofilms to disassemble. Because of
      these potential biofilm-destabilizing effects, we also hypothesized that L
      arginine might enhance the efficacy of antimicrobials that normally cannot
      rapidly penetrate biofilms. A static microplate biofilm system and a controlled
      flow microfluidic system were used to develop multi-species oral biofilms derived
      from pooled unfiltered cell-containing saliva (CCS) in pooled filter-sterilized
      cell-free saliva (CFS) at 37 degrees  C. The addition of pH neutral L-arginine
      monohydrochloride (LAHCl) to CFS was found to exert negligible antimicrobial
      effects but significantly altered biofilm architecture in a concentration
      dependent manner. Under controlled flow, the biovolume of biofilms
      (MUm(3)/MUm(2)) developed in saliva containing 100-500 mM LAHCl were up to two
      orders of magnitude less than when developed without LAHCI. Culture-independent
      community analysis demonstrated that 500 mM LAHCl substantially altered biofilm
      species composition: the proportion of Streptococcus and Veillonella species
      increased and the proportion of Gram-negative bacteria such as Neisseria and
      Aggregatibacter species was reduced. Adding LAHCl to pre-formed biofilms also
      reduced biovolume, presumably by altering cell-cell interactions and causing cell
      detachment. Furthermore, supplementing 0.01% cetylpyridinium chloride (CPC), an
      antimicrobial commonly used for the treatment of dental plaque, with 500 mM LAHCl
      resulted in greater penetration of CPC into the biofilms and significantly
      greater killing compared to a non-supplemented 0.01% CPC solution. Collectively,
      this work demonstrates that LAHCl moderates multi-species oral biofilm
      development and community composition and enhances the activity of CPC. The
      incorporation of LAHCl into oral healthcare products may be useful for enhanced
      biofilm control.

PMID- 25946041
TI  - Commensal Streptococcus salivarius Modulates PPARgamma Transcriptional Activity
      in Human Intestinal Epithelial Cells.
AB  - The impact of commensal bacteria in eukaryotic transcriptional regulation has
      increasingly been demonstrated over the last decades. A multitude of studies have
      shown direct effects of commensal bacteria from local transcriptional activity to
      systemic impact. The commensal bacterium Streptococcus salivarius is one of the
      early bacteria colonizing the oral and gut mucosal surfaces. It has been shown to
      down-regulate nuclear transcription factor (NF-kB) in human intestinal cells, a
      central regulator of the host mucosal immune system response to the microbiota.
      In order to evaluate its impact on a further important transcription factor shown
      to link metabolism and inflammation in the intestine, namely PPARgamma
      (peroxisome proliferator-activated receptor), we used human intestinal epithelial
      cell-lines engineered to monitor PPARgamma transcriptional activity in response
      to a wide range of S. salivarius strains. We demonstrated that different strains
      from this bacterial group share the property to inhibit PPARgamma activation
      independently of the ligand used. First attempts to identify the nature of the
      active compounds showed that it is a low-molecular-weight, DNase-, proteases- and
      heat-resistant metabolite secreted by S. salivarius strains. Among PPARgamma
      targeted metabolic genes, I-FABP and Angptl4 expression levels were dramatically
      reduced in intestinal epithelial cells exposed to S. salivarius supernatant. Both
      gene products modulate lipid accumulation in cells and down-regulating their
      expression might consequently affect host health. Our study shows that species
      belonging to the salivarius group of streptococci impact both host inflammatory
      and metabolic regulation suggesting a possible role in the host homeostasis and
      health. 

PMID- 25946042
TI  - Characterization of a Novel Mouse Model of Alzheimer's Disease--Amyloid Pathology
      and Unique beta-Amyloid Oligomer Profile.
AB  - Amyloid plaques composed of beta-amyloid (Abeta) protein are a pathological
      hallmark of Alzheimer's disease. We here report the generation and
      characterization of a novel transgenic mouse model of Abeta toxicity. The rTg9191
      mice harbor a transgene encoding the 695 amino-acid isoform of human amyloid
      precursor protein (APP) with the Swedish and London mutations (APPNLI) linked to
      familial Alzheimer's disease, under the control of a tetracycline-response
      element, as well as a transgene encoding the tetracycline transactivator, under
      the control of the promoter for calcium-calmodulin kinase IIalpha. In these mice,
      APPNLI is expressed at a level four-fold that of endogenous mouse APP and its
      expression is restricted to forebrain regions. Transgene expression was
      suppressed by 87% after two months of doxycycline administration. Histologically,
      we showed that (1) Abeta plaques emerged in cerebral cortex and hippocampus as
      early as 8 and 10.5-12.5 months of age, respectively; (2) plaque deposition
      progressed in an age-dependent manner, occupying up to 19% of cortex at ~25
      months of age; and (3) neuropathology--such as abnormal neuronal architecture,
      tau hyperphosphorylation and misfolding, and neuroinflammation--was observed in
      the vicinity of neuritic plaques. Biochemically, we determined total Abeta
      production at varied ages of mice, and we showed that mice produced primarily
      fibrillar Abeta assemblies recognized by conformation-selective OC antibodies,
      but few non-fibrillar oligomers (e.g., Abeta*56) detectable by A11 antibodies.
      Finally, we showed that expression of the tetracycline transactivator resulted in
      reduced brain weight and smaller dentate-gyrus size. Collectively, these data
      indicate that rTg9191 mice may serve as a model for studying the neurological
      effects of the fibrillar Abeta assemblies in situ.

PMID- 25946044
TI  - Correction: Orphan Nuclear Receptor Errgamma Induces C-Reactive Protein Gene
      Expression through Induction of ER-Bound Bzip Transmembrane Transcription Factor
      CREBH.

PMID- 25946043
TI  - Deletion of 15q11.2(BP1-BP2) region: further evidence for lack of phenotypic
      specificity in a pediatric population.
AB  - Microdeletion of the BP1-BP2 region at 15q11.2 is a recurrent copy number variant
      (CNV) frequently found in patients undergoing chromosomal microarray (CMA).
      Genetic counselling regarding this CNV is challenging due to the wide range of
      phenotypic presentation in reported patients and lack of general population-based
      data. As one of the most common reasons for CMA is childhood developmental delay,
      clinicians need to be cognizant of the inherent ascertainment bias in the
      literature. We performed a detailed medical record review for 55 patients with
      this 15q11.2 microdeletion and report the clinical features of the 35 patients
      for whom information was available. We compared our results to the recent report
      by Cafferkey et al. in this journal. Our conclusion is that the phenotypic
      spectrum is too broad and non-specific to constitute a bona fide "syndrome" and
      that further research must be done to delineate the contribution of this CNV to
      phenotype.

PMID- 25946045
TI  - Initial Evidence for Adaptive Selection on the NADH Subunit Two of Freshwater
      Dolphins by Analyses of Mitochondrial Genomes.
AB  - A small number of cetaceans have adapted to an entirely freshwater environment,
      having colonized rivers in Asia and South America from an ancestral origin in the
      marine environment. This includes the 'river dolphins', early divergence from the
      odontocete lineage, and two species of true dolphins (Family Delphinidae).
      Successful adaptation to the freshwater environment may have required increased
      demands in energy involved in processes such as the mitochondrial osmotic
      balance. For this reason, riverine odontocetes provide a compelling natural
      experiment in adaptation of mammals from marine to freshwater habitats. Here we
      present initial evidence of positive selection in the NADH dehydrogenase subunit
      2 of riverine odontocetes by analyses of full mitochondrial genomes, using tests
      of selection and protein structure modeling. The codon model with highest
      statistical support corresponds to three discrete categories for amino acid
      sites, those under positive, neutral, and purifying selection. With this model we
      found positive selection at site 297 of the NADH dehydrogenase subunit 2
      (dN/dS>1.0,) leading to a substitution of an Ala or Val from the ancestral state
      of Thr. A phylogenetic reconstruction of 27 cetacean mitogenomes showed that an
      Ala substitution has evolved at least four times in cetaceans, once or more in
      the three 'river dolphins' (Families Pontoporidae, Lipotidae and Inidae), once in
      the riverine Sotalia fluviatilis (but not in its marine sister taxa), once in the
      riverine Orcaella brevirostris from the Mekong River (but not in its marine
      sister taxa) and once in two other related marine dolphins. We located the
      position of this amino acid substitution in an alpha-helix channel in the trans
      membrane domain in both the E. coli structure and Sotalia fluviatilis model. In
      E. coli this position is located in a helix implicated in a proton translocation
      channel of respiratory complex 1 and may have a similar role in the NADH
      dehydrogenases of cetaceans. 

PMID- 25946046
TI  - Espresso coffee consumption and risk of coronary heart disease in a large Italian
      cohort.
AB  - BACKGROUND: The relationship between coffee consumption and coronary heart
      disease (CHD) has been investigated in several studies with discrepant results.
      We examined the association between Italian-style (espresso and mocha) coffee
      consumption and CHD risk. METHODS: We investigated 12,800 men and 30,449 women
      without history of cardiovascular disease recruited to the EPICOR prospective
      cohort study. Coffee consumption was assessed at baseline. In a random sub-cohort
      of 1472 subjects, plasma triglycerides, and total, LDL and HDL cholesterol were
      determined to investigate the effect of coffee consumption on plasma lipids.
      RESULTS: After a mean follow up of 10.9 years, 804 cases of CHD (500 acute
      events, 56 fatal events and 248 revascularizations, all first events) were
      identified. Multivariable adjusted hazard ratios for CHD were: 1.18 (95% CI 0.87
      1.60) for drinking 1-2 cups/day, 1.37 (95% CI 1.03-1.82) for >2-4 cups/day and
      1.52 (95% CI 1.11-2.07) for over 4 cups/day (P trend <0.001) compared to
      reference (<1 cup/day). Plasma triglycerides, and total, LDL and HDL cholesterol
      did not vary significantly (ANOVA) with coffee consumption. CONCLUSION:
      Consumption of over 2 cups/day of Italian-style coffee is associated with
      increased CHD risk, but coffee consumption was not associated with plasma lipid
      changes, so the adverse effect of consumption appears unrelated to lipid profile.

PMID- 25946047
TI  - Complication rates after functional endoscopic sinus surgery: analysis of 50,734
      Japanese patients.
AB  - OBJECTIVE: The complication rates associated with different types of functional
      endoscopic sinus surgery (FESS) remain to be fully examined. STUDY DESIGN:
      Retrospective cohort study. METHODS: We extracted data from the Japanese
      Diagnosis Procedure Combination database on 50,734 patients (aged >= 16 years)
      who underwent FESS for chronic rhinosinusitis between 2007 and 2013. We focused
      on specific types of surgery and stratified the patients into three groups: group
      1 (single sinus surgery), group 2 (multiple sinus surgery), and group 3 (whole
      sinus surgery). Patient characteristics and early postoperative complications
      including cerebrospinal fluid (CSF) leakage, orbital injury, severe hemorrhage,
      and toxic shock syndrome (TSS) that occurred during 1 to 2 weeks of each
      hospitalization were compared. Multivariable logistic regression analysis was
      performed to assess the association between overall complication rate and
      background characteristics, with adjustment for within-hospital clustering.
      RESULTS: The overall complication rate was 0.50%; the rates of CSF leakage,
      orbital injury, hemorrhage requiring surgery, blood transfusion, and TSS were
      0.09%, 0.09%, 0.10%, 0.18%, and 0.02%, respectively. Ethmoidectomy combined with
      sphenoidotomy was associated with higher overall complication rates (1.40%). The
      rate of orbital injury was highest in group 2, whereas that of other
      complications did not differ significantly among the groups. Extent of FESS
      showed no significant association with overall complication rate. CONCLUSION:
      More extensive FESS was not associated with increased rates of postoperative CSF
      leakage, hemorrhage, or TSS. Multiple sinus surgery was associated with a higher
      rate of orbital injury. The extent of surgery did not significantly affect the
      overall complication rate. LEVEL OF EVIDENCE: 2b.

PMID- 25946048
TI  - Abl Kinases Regulate HGF/Met Signaling Required for Epithelial Cell Scattering,
      Tubulogenesis and Motility.
AB  - Tight regulation of receptor tyrosine kinases (RTKs) is crucial for normal
      development and homeostasis. Dysregulation of RTKs signaling is associated with
      diverse pathological conditions including cancer. The Met RTK is the receptor for
      hepatocyte growth factor (HGF) and is dysregulated in numerous human tumors. Here
      we show that Abl family of non-receptor tyrosine kinases, comprised of Abl (ABL1)
      and Arg (ABL2), are activated downstream of the Met receptor, and that inhibition
      of Abl kinases dramatically suppresses HGF-induced cell scattering and
      tubulogenesis. We uncover a critical role for Abl kinases in the regulation of
      HGF/Met-dependent RhoA activation and RhoA-mediated actomyosin contractility and
      actin cytoskeleton remodeling in epithelial cells. Moreover, treatment of breast
      cancer cells with Abl inhibitors markedly decreases Met-driven cell migration and
      invasion. Notably, expression of a transforming mutant of the Met receptor in the
      mouse mammary epithelium results in hyper-activation of both Abl and Arg kinases.
      Together these data demonstrate that Abl kinases link Met activation to Rho
      signaling and Abl kinases are required for Met-dependent cell scattering,
      tubulogenesis, migration, and invasion. Thus, inhibition of Abl kinases might be
      exploited for the treatment of cancers driven by hyperactivation of HGF/Met
      signaling. 

PMID- 25946049
TI  - The Ochoa urofacial syndrome: recognize the peculiar smile and avoid severe
      urological and renal complications.
AB  - Ochoa syndrome is rare and its major clinical problems frequently unrecognized.
      We describe facial characteristics of six patients to help health professional
      recognize the inverted smile that these patients present and refer them to proper
      treatment. Patients' medical records were reviewed and patients' urological
      status clinically reassessed. At last evaluation patients' mean age was 15.5
      years, and age ranged from 12 to 32 years. Mean follow-up was 35 months (12 to
      60). Initial symptoms were urinary tract infections in four patients (67%)
      associated with enuresis and incontinence in three of them (50%). One patient had
      only urinary tract infection and two lower urinary tract symptoms without
      infections. Initial treatment consisted of clean intermittent catheterization
      with anticholinergics for all patients. Four patients (67%) were submitted to
      bladder augmentation. Two patients had end-stage renal disease during follow-up,
      one received kidney transplantation and one patient remained on the waiting list
      for a renal transplantation. Familial consanguinity was present in only one case.
      This significant condition is rare, but it must be recognized by pediatricians,
      nephrologists and urologists in order to institute early aggressive urological
      treatment. 

PMID- 25946050
TI  - Renal hemangiopericytoma: case report and literature review.
AB  - Hemangioperycytoma is a rare perivascular tumor that seldom involves the
      urogenital system. This tumor often appears with an unspecific clinical picture,
      and sometimes is associated with hematuria or hypertension. Diagnosis is based on
      a combination of histological and immunohistological findings. We report a case
      of a 52-year-old patient with renal hemangiopericytoma who underwent surgical
      treatment at our service. This report also includes a literature review on the
      subject. 

PMID- 25946051
TI  - Vitreomacular traction syndrome.

PMID- 25946052
TI  - Outpatient treatment of sleep disorders in Alzheimer patients.
AB  - Sleep disorders are common in patients with Alzheimer dementia and affect the
      quality of life of patients and of their caregivers. Despite the rising number of
      studies in the area, almost all of them are about non-pharmacological treatment.
      Our objective was to review the literature concerning pharmacological and non
      pharmacological approaches to treat sleep disorders of elderly patients with
      Alzheimer dementia in the ambulatory setting. The treatments revised consisted of
      sleep hygiene and/or use of intense light coupled or not with use of melatonin,
      cholinesterase inhibitors, antipsychotics, hypnotics or antidepressants. In
      addition to the non-pharmacological measures, there is evidence that the use of
      trazodone may aid the treatment of sleep disorders of older individuals with
      Alzheimer dementia. More studies are necessary to examine the non-pharmacological
      and pharmacological treatments revised herein. 

PMID- 25946053
TI  - Oral care and nosocomial pneumonia: a systematic review.
AB  - To perform a systematic review of the literature on the control of oral biofilms
      and the incidence of nosocomial pneumonia, in addition to assessing and
      classifying studies as to the grade of recommendation and level of evidence. The
      review was based on PubMed, LILACS, and Scopus databases, from January 1st, 2000
      until December 31st, 2012. Studies evaluating oral hygiene care related to
      nosocomial infections in patients hospitalized in intensive care units were
      selected according to the inclusion criteria. Full published articles available
      in English, Spanish, or Portuguese, which approached chemical or mechanical oral
      hygiene techniques in preventing pneumonia, interventions performed, and their
      results were included. After analysis, the articles were classified according to
      level of evidence and grade of recommendation according to the criteria of the
      Oxford Centre for Evidence-Based Medicine. A total of 297 abstracts were found,
      14 of which were full articles that met our criteria. Most articles included a
      study group with chlorhexidine users and a control group with placebo users for
      oral hygiene in the prevention of pneumonia. All articles were classified as B in
      the level of evidence, and 12 articles were classified as 2B and two articles as
      2C in grade of recommendation. It was observed that the control of oral biofilm
      reduces the incidence of nosocomial pneumonia, but the fact that most articles
      had an intermediate grade of recommendation makes clear the need to conduct
      randomized controlled trials with minimal bias to establish future guidelines for
      oral hygiene in intensive care units. 

PMID- 25946054
TI  - Is There an Association Between the Body Mass Index and Interpersonal Violent
      Behavior?
AB  - An inverse relationship between the body mass index (BMI) and the risk of
      completed suicide was shown in several studies. Furthermore, it is suggested that
      obesity might be associated with a lower risk for violent criminality. Therefore,
      the aim of this study was to analyze whether a higher BMI is associated with a
      lower risk for being arrested due to violent behavior in a sample of 43,992 male
      offenders. Multinomial logistic regression analysis was applied to assess the
      relationship between different BMI categories and categories of committed crime
      as outcome variable by including various covariates. Our results indicated that
      compared to a normal BMI a higher BMI was associated with a significantly lower
      risk for being arrested in different crime categories associated with
      interpersonal violence, such as crimes against life and limb (for example: odds
      ratio=0.60, CI 95%: 0.52-0.69 for 30-34.9 kg/m2).

PMID- 25946056
TI  - Relativistic environmental effects in (29)Si NMR chemical shifts of halosilanes:
      light nucleus, heavy environment.
AB  - Relativistic calculations of (29)Si NMR shielding constants (chemical shifts) in
      the series of halosilanes SiX(n)H(4-n) (X = F, Cl, Br and I) are performed within
      a full four-component relativistic Dirac's scheme using relativistic Dyall's
      basis sets. Three different theoretical levels are tested in the computation of
      (29)Si NMR chemical shifts in comparison with experiment: namely, four-component
      relativistic GIAO-DFT, four-component relativistic GIAO-RPA, and a hybrid scheme
      of a nonrelativistic GIAO-MP2 with taking into account relativistic corrections
      using the four-component relativistic GIAO-RPA. The DFT results give larger
      relativistic effects as compared to the RPA data which might be rationalized in
      terms of the manifestation of correlation effects taken into account at the DFT
      level and not accounted for at the uncorrelated RPA level. Taking into account
      solvent effects slightly improves agreement with experiment, however, being not a
      matter of principle. Generally, relativistic pure nonempirical wave function
      methods perform much better as compared to relativistic DFT methods when
      benchmarked to experiment.

PMID- 25946057
TI  - Responses of dune plant communities to continental uplift from a major
      earthquake: sudden releases from coastal squeeze.
AB  - Vegetated dunes are recognized as important natural barriers that shelter inland
      ecosystems and coastlines suffering daily erosive impacts of the sea and extreme
      events, such as tsunamis. However, societal responses to erosion and shoreline
      retreat often result in man-made coastal defence structures that cover part of
      the intertidal and upper shore zones causing coastal squeeze and habitat loss,
      especially for upper shore biota, such as dune plants. Coseismic uplift of up to
      2.0 m on the Peninsula de Arauco (South central Chile, ca. 37.5o S) caused by the
      2010 Maule earthquake drastically modified the coastal landscape, including major
      increases in the width of uplifted beaches and the immediate conversion of mid to
      low sandy intertidal habitat to supralittoral sandy habitat above the reach of
      average tides and waves. To investigate the early stage responses in species
      richness, cover and across-shore distribution of the hitherto absent dune plants,
      we surveyed two formerly intertidal armoured sites and a nearby intertidal
      unarmoured site on a sandy beach located on the uplifted coast of Llico
      (Peninsula de Arauco) over two years. Almost 2 years after the 2010 earthquake,
      dune plants began to recruit, then rapidly grew and produced dune hummocks in the
      new upper beach habitats created by uplift at the three sites. Initial vegetation
      responses were very similar among sites. However, over the course of the study,
      the emerging vegetated dunes of the armoured sites suffered a slowdown in the
      development of the spatial distribution process, and remained impoverished in
      species richness and cover compared to the unarmoured site. Our results suggest
      that when released from the effects of coastal squeeze, vegetated dunes can
      recover without restoration actions. However, subsequent human activities and
      management of newly created beach and dune habitats can significantly alter the
      trajectory of vegetated dune development. Management that integrates the effects
      of natural and human induced disturbances, and promotes the development of dune
      vegetation as natural barriers can provide societal and conservation benefits in
      coastal ecosystems. 

PMID- 25946055
TI  - Patient-specific detection of cerebral blood flow alterations as assessed by
      arterial spin labeling in drug-resistant epileptic patients.
AB  - Electrophysiological and hemodynamic data can be integrated to accurately and
      precisely identify the generators of abnormal electrical activity in drug
      resistant focal epilepsy. Arterial Spin Labeling (ASL), a magnetic resonance
      imaging (MRI) technique for quantitative noninvasive measurement of cerebral
      blood flow (CBF), can provide a direct measure of variations in cerebral
      perfusion associated with the epileptic focus. In this study, we aimed to confirm
      the ASL diagnostic value in the identification of the epileptogenic zone, as
      compared to electrical source imaging (ESI) results, and to apply a template
      based approach to depict statistically significant CBF alterations. Standard
      video-electroencephalography (EEG), high-density EEG, and ASL were performed to
      identify clinical seizure semiology and noninvasively localize the epileptic
      focus in 12 drug-resistant focal epilepsy patients. The same ASL protocol was
      applied to a control group of 17 healthy volunteers from which a normal perfusion
      template was constructed using a mixed-effect approach. CBF maps of each patient
      were then statistically compared to the reference template to identify perfusion
      alterations. Significant hypo- and hyperperfused areas were identified in all
      cases, showing good agreement between ASL and ESI results. Interictal
      hypoperfusion was observed at the site of the seizure in 10/12 patients and early
      postictal hyperperfusion in 2/12. The epileptic focus was correctly identified
      within the surgical resection margins in the 5 patients who underwent lobectomy,
      all of which had good postsurgical outcomes. The combined use of ESI and ASL can
      aid in the noninvasive evaluation of drug-resistant epileptic patients. 

PMID- 25946058
TI  - Transcatheter tricuspid valve-in-valve in patients with transvalvular device
      leads.
AB  - OBJECTIVE: To describe the effects of percutaneously implanted valve-in-valve in
      the tricuspid position for patients with pre-existing transvalvular device leads.
      METHODS: In this case series, we describe implantation of the Melody valve and
      SAPIEN XT valve within dysfunctional bioprosthetic tricuspid valves in three
      patients with transvalvular device leads. RESULTS: In all cases, the valve was
      successfully deployed and device lead function remained unchanged. In 1/3 cases
      with 6-month follow-up, device lead parameters remain unchanged and transcatheter
      valve-in-valve function remains satisfactory. CONCLUSIONS: Transcatheter
      tricuspid valve-in-valve is feasible in patients with pre-existing transvalvular
      devices leads. Further study is required to determine the long-term clinical
      implications of this treatment approach.

PMID- 25946059
TI  - Intrathoracic pressure regulation to treat intraoperative hypotension: A phase II
      pilot study.
AB  - BACKGROUND: Intraoperative hypotension secondary to acute blood loss and fluid
      shifts increases morbidity and mortality. Intrathoracic pressure regulation (IPR)
      is a new therapy that enhances circulation by increasing venous return with a
      negative intrathoracic pressure created noninvasively, either actively (vacuum
      source or patient inspiration) or passively (chest recoil during cardiopulmonary
      resuscitation). OBJECTIVE: In this Phase II pilot study, we tested the hypothesis
      that active IPR therapy would improve the haemodynamic status of patients who
      developed clinically significant hypotension during abdominal surgery. DESIGN: A
      phase II, single cohort, interventional pilot study. SETTING: University of
      Minnesota Fairview Hospital. PATIENTS: Twenty-two patients [American Society of
      Anesthesiologists (ASA) physical status I to III] were enrolled prospectively of
      whom 15 experienced intraoperative hypotension. INTERVENTION: If intraoperative
      hypotension occurred more than 10 min after induction, the IPR device was applied
      immediately for a minimum of 10 min. MAIN OUTCOME MEASURE: The hypotensive SBP
      immediately before the start of IPR treatment was compared with the SBP obtained
      at the end of IPR therapy. The paired Student's t-test was used to determine
      statistical significance (P < 0.05). RESULTS: Fifteen of the 22 patients enrolled
      experienced 18 hypotensive episodes, which were treated with at least 10 min of
      IPR therapy. Fourteen episodes responded to IPR alone and four episodes (four
      patients) required additional fluid and vasopressor therapy to treat the
      hypotension. The group mean +/- SD SBPs at the onset of the IPR treatment and at
      the end of IPR treatment were 90.7 +/- 9.7 and 98.4 +/- 17.4 mmHg (P = 0.02),
      respectively. The maximum SBP reached during the treatment was 105.6 +/- 19.6
      mmHg. Pulse pressure increased from 36.8 +/- 8.5 mmHg immediately before IPR
      treatment to 41.5 +/- 11.1 mmHg (P = 0.02) at the end of IPR treatment. Mean
      arterial pressure (MAP) increased from 66.3 +/- 9.4 mmHg immediately before IPR
      treatment to 71.5 +/- 14.4 mmHg (P = 0.03) at the end of IPR treatment. No
      adverse events were identified with use of the IPR device. CONCLUSION: IPR may be
      useful in treating intraoperative hypotension without additional fluid or
      vasopressor therapy. No significant adverse events were observed. On the basis of
      this phase II pilot study, a larger study is justified.

PMID- 25946060
TI  - Airway obstruction in the postanaesthetic care unit of a tertiary care centre: A
      prospective audit.

PMID- 25946061
TI  - Selective vs Nonselective Nonsteroidal Anti-inflammatory Drugs and Anastomotic
      Leakage After Colorectal Surgery.

PMID- 25946065
TI  - Magnitude and Predictors of Anti-Retroviral Treatment (ART) Failure in Private
      Health Facilities in Addis Ababa, Ethiopia.
AB  - BACKGROUND: The public health approach to antiretroviral treatment management
      encourages the public private partnership in resource limited countries like
      Ethiopia. As a result, some private health facilities are accredited to provide
      antiretroviral treatment free services. Evidence on magnitude and predictors of
      treatment failure are crucial for timely actions. However, there are few studies
      in this regard. OBJECTIVE: To assess the magnitude and predictors of ART failure
      in private health facilities in Addis Ababa, Ethiopia. METHODS: The study
      followed retrospective cohort design, with 525 adult antiretroviral treatment
      clients who started the treatment since October 2009 and have at least six months
      follow up until December 31, 2013. Kaplan Meier survival analysis and Cox
      proportional hazard model were used for analysis. RESULTS: Treatment failure,
      using the three WHO antiretroviral treatment failure criteria, was 19.8%. The
      immunologic, clinical, and virologic failures were 15%, 6.3% and 1.3%
      respectively. The mean and median survival times in months were 41.17 with 95%
      Confidence Interval (CI) [39.69, 42.64] and 49.00, 95% CI [47.71, 50.29]
      respectively. The multivariate cox regression analysis showed years since HIV
      diagnosis (Adjusted Hazard Ratio (AHR)=13.87 with 95% CI [6.65, 28.92]),
      disclosure (AHR=0.59, 95% CI [0.36, 0.96]), WHO stage at start (AHR=1.84, 95% CI
      [1.16, 2.93]), weight at baseline (AHR=0.58, 95% CI [0.38, 0.89]), and
      functionality status at last visit (AHR=2.57, 95% CI [1.59, 4.15]) were
      independent predictors of treatment failure. CONCLUSION: The study showed that
      the treatment failure is high among the study subjects. The predictors for
      antiretroviral treatment failure were years since HIV diagnosis, weight at start,
      WHO stage at start, status at last visit and disclosure. RECOMMENDATIONS:
      Facilities need to monitor antiretroviral treatment clients to avoid disease
      progression and drug resistance.

PMID- 25946066
TI  - Systems approaches to design of targeted therapeutic delivery.
AB  - Targeted drug delivery aims to improve therapeutic effects and enable mechanisms
      that are not feasible for untargeted agents (e.g., due to impermeable biological
      barriers). To achieve targeting, a drug or its carrier should possess properties
      providing specific accumulation from circulation at the desired site. There are
      several examples of systems-inspired approaches that have been applied to achieve
      this goal. First, proteomics analysis of plasma membrane fraction of the vascular
      endothelium has identified a series of target molecules and their ligands (e.g.,
      antibodies) that deliver conjugated cargoes to well-defined vascular cells and
      subcellular compartments. Second, selection of ligands binding to cells of
      interest using phage display libraries in vitro and in vivo has provided peptides
      and polypeptides that bind to normal and pathologically altered cells. Finally,
      large-scale high-throughput combinatorial synthesis and selection of lipid- and
      polymer-based nanocarriers varying their chemical components has yielded a series
      of carriers accumulating in diverse organs and delivering RNA interference agents
      to diverse cells. Together, these approaches offer a basis for systems-based
      design and selection of targets, targeting molecules, and targeting vehicles.
      Current studies focus on expanding the arsenal of these and alternative targeting
      strategies, devising drug delivery systems capitalizing on these strategies and
      evaluation of their benefit/risk ratio in adequate animal models of human
      diseases. These efforts, combined with better understanding of mechanisms and
      unintended consequences of these targeted interventions, need to be ultimately
      translated into industrial development and the clinical domain.

PMID- 25946067
TI  - Reconciling West Nile virus with the autophagic pathway.
AB  - West Nile virus (WNV) is a neurotropic mosquito-borne flavivirus responsible for
      recurrent outbreaks of meningitis and encephalitis. Several studies analyzing the
      interactions of this pathogen with the autophagic pathway have reported opposite
      results with evidence for and against the upregulation of autophagy in infected
      cells. In this regard, we have recently reported that minimal genetic changes
      (single amino acid substitutions) in nonstructural proteins of WNV can modify the
      ability of the virus to induce autophagic features such as LC3 modification and
      aggregation in infected cells. We think that these results could help explain
      some of the previously reported discrepancies. These findings could also aid in
      deciphering the interactions of this pathogen with the autophagic pathway at the
      molecular level aimed to develop feasible antiviral strategies to combat this
      pathogen, and other related flaviviruses. 

PMID- 25946068
TI  - Spatial heterogeneity in soil microbes alters outcomes of plant competition.
AB  - Plant species vary greatly in their responsiveness to nutritional soil
      mutualists, such as mycorrhizal fungi and rhizobia, and this responsiveness is
      associated with a trade-off in allocation to root structures for resource uptake.
      As a result, the outcome of plant competition can change with the density of
      mutualists, with microbe-responsive plant species having high competitive ability
      when mutualists are abundant and non-responsive plants having high competitive
      ability with low densities of mutualists. When responsive plant species also
      allow mutualists to grow to greater densities, changes in mutualist density can
      generate a positive feedback, reinforcing an initial advantage to either plant
      type. We study a model of mutualist-mediated competition to understand outcomes
      of plant-plant interactions within a patchy environment. We find that a microbe
      responsive plant can exclude a non-responsive plant from some initial conditions,
      but it must do so across the landscape including in the microbe-free areas where
      it is a poorer competitor. Otherwise, the non-responsive plant will persist in
      both mutualist-free and mutualist-rich regions. We apply our general findings to
      two different biological scenarios: invasion of a non-responsive plant into an
      established microbe-responsive native population, and successional replacement of
      non-responders by microbe-responsive species. We find that resistance to invasion
      is greatest when seed dispersal by the native plant is modest and dispersal by
      the invader is greater. Nonetheless, a native plant that relies on microbial
      mutualists for competitive dominance may be particularly vulnerable to invasion
      because any disturbance that temporarily reduces its density or that of the
      mutualist creates a window for a non-responsive invader to establish dominance.
      We further find that the positive feedbacks from associations with beneficial
      soil microbes create resistance to successional turnover. Our theoretical results
      constitute an important first step toward developing a general understanding of
      the interplay between mutualism and competition in patchy landscapes, and
      generate qualitative predictions that may be tested in future empirical studies. 

PMID- 25946069
TI  - Improvement of glycemic control in streptozotocin-induced diabetic rats by
      Atlantic salmon skin gelatin hydrolysate as the dipeptidyl-peptidase IV
      inhibitor.
AB  - In our previous study, Atlantic salmon skin gelatin hydrolysed with flavourzyme
      possessed 42.5% dipeptidyl-peptidase (DPP)-IV inhibitory activity at a
      concentration of 5 mg mL(-1). The oral administration of the hydrolysate (FSGH)
      at a single dose of 300 mg per day in streptozotocin (STZ)-induced diabetic rats
      for 5 weeks was evaluated for its antidiabetic effect. During the 5-week
      experiment, body weight increased, and the food and water intake was reduced by
      FSGH in diabetic rats. The daily administration of FSGH for 5 weeks was effective
      for lowering the blood glucose levels of diabetic rats during an oral glucose
      tolerance test (OGTT). After the 5-week treatment, plasma DPP-IV activity was
      inhibited; the plasma activity of glucagon-like peptide-1 (GLP-1), insulin, and
      the insulin-to-glucagon ratio were increased by FSGH in diabetic rats. The
      results indicate that FSGH has the function of inhibiting GLP-1 degradation by
      DPP-IV, resulting in the enhancement of insulin secretion and improvement of
      glycemic control in STZ-induced diabetic rats.

PMID- 25946070
TI  - An Atypical Mitochondrial Carrier That Mediates Drug Action in Trypanosoma
      brucei.
AB  - Elucidating the mechanism of action of trypanocidal compounds is an important
      step in the development of more efficient drugs against Trypanosoma brucei. In a
      screening approach using an RNAi library in T. brucei bloodstream forms, we
      identified a member of the mitochondrial carrier family, TbMCP14, as a prime
      candidate mediating the action of a group of anti-parasitic choline analogs.
      Depletion of TbMCP14 by inducible RNAi in both bloodstream and procyclic forms
      increased resistance of parasites towards the compounds by 7-fold and 3-fold,
      respectively, compared to uninduced cells. In addition, down-regulation of
      TbMCP14 protected bloodstream form mitochondria from a drug-induced decrease in
      mitochondrial membrane potential. Conversely, over-expression of the carrier in
      procyclic forms increased parasite susceptibility more than 13-fold. Metabolomic
      analyses of parasites over-expressing TbMCP14 showed increased levels of the
      proline metabolite, pyrroline-5-carboxylate, suggesting a possible involvement of
      TbMCP14 in energy production. The generation of TbMCP14 knock-out parasites
      showed that the carrier is not essential for survival of T. brucei bloodstream
      forms, but reduced parasite proliferation under standard culture conditions. In
      contrast, depletion of TbMCP14 in procyclic forms resulted in growth arrest,
      followed by parasite death. The time point at which parasite proliferation
      stopped was dependent on the major energy source, i.e. glucose versus proline, in
      the culture medium. Together with our findings that proline-dependent ATP
      production in crude mitochondria from TbMCP14-depleted trypanosomes was reduced
      compared to control mitochondria, the study demonstrates that TbMCP14 is involved
      in energy production in T. brucei. Since TbMCP14 belongs to a trypanosomatid
      specific clade of mitochondrial carrier family proteins showing very poor
      similarity to mitochondrial carriers of mammals, it may represent an interesting
      target for drug action or targeting. 

PMID- 25946072
TI  - Sleep, Travel, and Recovery Responses of National Footballers During and After
      Long-Haul International Air Travel.
AB  - PURPOSE: The current study examined the sleep, travel, and recovery responses of
      elite footballers during and after long-haul international air travel, with a
      further description of these responses over the ensuing competitive tour
      (including 2 matches). METHODS: In an observational design, 15 elite male
      football players undertook 18 h of predominantly westward international air
      travel from the United Kingdom to South America (-4-h time-zone shift) for a 10-d
      tour. Objective sleep parameters, external and internal training loads,
      subjective player match performance, technical match data, and perceptual jet-lag
      and recovery measures were collected. RESULTS: Significant differences were
      evident between outbound travel and recovery night 1 (night of arrival; P < .001)
      for sleep duration. Sleep efficiency was also significantly reduced during
      outbound travel compared with recovery nights 1 (P = .001) and 2 (P = .004).
      Furthermore, both match nights (5 and 10), showed significantly less sleep than
      nonmatch nights 2 to 4 and 7 to 9 (all P < .001). No significant differences were
      evident between baseline and any time point for all perceptual measures of jet
      lag and recovery (P > .05), although large effects were evident for jet-lag on d
      2 (2 d after arrival). CONCLUSIONS: Sleep duration is truncated during long-haul
      international travel with a 4-h time-zone delay and after night matches in elite
      footballers. However, this lost sleep appeared to have a limited effect on
      perceptual recovery, which may be explained by a westbound flight and a
      relatively small change in time zones, in addition to the significant increase in
      sleep duration on the night of arrival after the long-haul flight.

PMID- 25946071
TI  - Pandemic Swine-Origin H1N1 Influenza Virus Replicates to Higher Levels and
      Induces More Fever and Acute Inflammatory Cytokines in Cynomolgus versus Rhesus
      Monkeys and Can Replicate in Common Marmosets.
AB  - The close immunological and physiological resemblance with humans makes non-human
      primates a valuable model for studying influenza virus pathogenesis and immunity
      and vaccine efficacy against infection. Although both cynomolgus and rhesus
      macaques are frequently used in influenza virus research, a direct comparison of
      susceptibility to infection and disease has not yet been performed. In the
      current study a head-to-head comparison was made between these species, by using
      a recently described swine-origin pandemic H1N1 strain, A/Mexico/InDRE4487/2009.
      In comparison to rhesus macaques, cynomolgus macaques developed significantly
      higher levels of virus replication in the upper airways and in the lungs,
      involving both peak level and duration of virus production, as well as higher
      increases in body temperature. In contrast, clinical symptoms, including
      respiratory distress, were more easily observed in rhesus macaques. Expression of
      sialyl-alpha-2,6-Gal saccharides, the main receptor for human influenza A
      viruses, was 50 to 73 times more abundant in trachea and bronchus of cynomolgus
      macaques relative to rhesus macaques. The study also shows that common marmosets,
      a New World non-human primate species, are susceptible to infection with pandemic
      H1N1. The study results favor the cynomolgus macaque as model for pandemic H1N1
      influenza virus research because of the more uniform and high levels of virus
      replication, as well as temperature increases, which may be due to a more
      abundant expression of the main human influenza virus receptor in the trachea and
      bronchi. 

PMID- 25946073
TI  - A study on liposomal encapsulation of a lipophilic prodrug of LHRH.
AB  - This study aimed at evaluating whether derivatization of luteinizing hormone
      releasing hormone (LHRH) peptide with an amphiphilic lipoamino acid moiety could
      allow, along with other technological and/or pharmacokinetic advantages, to
      improve its encapsulation in liposomes, potentially driving its further body
      distribution and cellular uptake. Experimental data confirmed that a lipophilic
      derivative of LHRH was efficiently incorporated in various liposomal systems,
      differing in lipid composition and surface charge, and obtained using different
      methods of production. Incubation of liposomes, loaded with a fluorescent
      derivative of the LHRH prodrug, with NCTC keratinocytes or Caco-2 cell cultures
      showed that the carriers can be rapidly internalized. Conversely, the
      internalization of the free prodrug occurred only at very high concentrations. 

PMID- 25946074
TI  - An arginine-functionalized stationary phase for hydrophilic interaction liquid
      chromatography.
AB  - An arginine-functionalized stationary phase for hydrophilic interaction liquid
      chromatography (HILIC) has been prepared for the first time by clicking arginine
      onto silica gel. It offers an efficient separation of organic acids, nucleotides
      and sugars. More interestingly, it exhibited excellent selectivity and enrichment
      toward acidic glycopeptides, even at a ratio of 1 : 150 to non-glycopeptides. 

PMID- 25946075
TI  - Atomic Defects in Two Dimensional Materials.
AB  - Atomic defects in crystalline structures have pronounced affects on their bulk
      properties. Aberration-corrected transmission electron microscopy has proved to
      be a powerful characterization tool for understanding the bonding structure of
      defects in materials. In this article, recent results on the characterization of
      defect structures in two dimensional materials are discussed. The dynamic
      behavior of defects in graphene shows the stability of zigzag edges of the
      material and gives insights into the dislocation motion. Polycrystalline graphene
      is characterized using advanced electron microscopy techniques, revealing the
      global crystal structure of the material, as well as atomic-resolution
      observation of the carbon atom positions between neighboring crystal grains.
      Studies of hexagonal boron nitride (hBN) are also visited, highlighting the
      interlayer bonding, which occurs upon defect formation, and characterization of
      grain boundary structures. Lastly, defect structures in monolayer polycrystalline
      transition metal dichalcogenides grown by CVD are discussed. 

PMID- 25946077
TI  - Effects of Trehalose on Thermodynamic Properties of Alpha-synuclein Revealed
      through Synchrotron Radiation Circular Dichroism.
AB  - Many neurodegenerative diseases, including Huntington's, Alzheimer's and
      Parkinson's diseases, are characterized by protein misfolding and aggregation.
      The capability of trehalose to interfere with protein misfolding and aggregation
      has been recently evaluated by several research groups. In the present work, we
      studied, by means of synchrotron radiation circular dichroism (SRCD)
      spectroscopy, the dose-effect of trehalose on alpha-synuclein conformation and/or
      stability to probe the capability of this osmolyte to interfere with alpha
      synuclein's aggregation. Our study indicated that a low trehalose concentration
      stabilized alpha-synuclein folding much better than at high concentration by
      blocking in vitro alpha-synuclein's polymerisation. These results suggested that
      trehalose could be associated with other drugs leading to a new approach for
      treating Parkinson's and other brain-related diseases. 

PMID- 25946076
TI  - The Role of Reactive Oxygen Species (ROS) in the Formation of Extracellular Traps
      (ETs) in Humans.
AB  - Extracellular traps (ETs) are reticulate structures of extracellular DNA
      associated with antimicrobial molecules. Their formation by phagocytes (mainly by
      neutrophils: NETs) has been identified as an essential element of vertebrate
      innate immune defense. However, as ETs are also toxic to host cells and potent
      triggers of autoimmunity, their role between pathogen defense and human
      pathogenesis is ambiguous, and they contribute to a variety of acute and chronic
      inflammatory diseases. Since the discovery of ET formation (ETosis) a decade ago,
      evidence has accumulated that most reaction cascades leading to ET release
      involve ROS. An important new facet was added when it became apparent that ETosis
      might be directly linked to, or be a variant of, the autophagy cell death
      pathway. The present review analyzes the evidence to date on the interplay
      between ROS, autophagy and ETosis, and highlights and discusses several further
      aspects of the ROS-ET relationship that are incompletely understood. These
      aspects include the role of NADPH oxidase-derived ROS, the molecular requirements
      of NADPH oxidase-dependent ETosis, the roles of NADPH oxidase subtypes,
      extracellular ROS and of ROS from sources other than NADPH oxidase, and the
      present evidence for ROS-independent ETosis. We conclude that ROS interact with
      ETosis in a multidimensional manner, with influence on whether ETosis shows
      beneficial or detrimental effects. 

PMID- 25946079
TI  - Aerodynamic performance of two-dimensional, chordwise flexible flapping wings at
      fruit fly scale in hover flight.
AB  - Fruit flies have flexible wings that deform during flight. To explore the fluid
      structure interaction of flexible flapping wings at fruit fly scale, we use a
      well-validated Navier-Stokes equation solver, fully-coupled with a structural
      dynamics solver. Effects of chordwise flexibility on a two dimensional hovering
      wing is studied. Resulting wing rotation is purely passive, due to the dynamic
      balance between aerodynamic loading, elastic restoring force, and inertial force
      of the wing. Hover flight is considered at a Reynolds number of Re = 100,
      equivalent to that of fruit flies. The thickness and density of the wing also
      corresponds to a fruit fly wing. The wing stiffness and motion amplitude are
      varied to assess their influences on the resulting aerodynamic performance and
      structural response. Highest lift coefficient of 3.3 was obtained at the lowest
      amplitude, highest-frequency motion (reduced frequency of 3.0) at the lowest
      stiffness (frequency ratio of 0.7) wing within the range of the current study,
      although the corresponding power required was also the highest. Optimal
      efficiency was achieved for a lower reduced frequency of 0.3 and frequency ratio
      0.35. Compared to the water tunnel scale with water as the surrounding fluid
      instead of air, the resulting vortex dynamics and aerodynamic performance
      remained similar for the optimal efficiency motion, while the structural response
      varied significantly. Despite these differences, the time-averaged lift scaled
      with the dimensionless shape deformation parameter gamma. Moreover, the wing
      kinematics that resulted in the optimal efficiency motion was closely aligned to
      the fruit fly measurements, suggesting that fruit fly flight aims to conserve
      energy, rather than to generate large forces.

PMID- 25946080
TI  - Free-radical chemistry as a means to evaluate lunar dust health hazard in view of
      future missions to the moon.
AB  - Lunar dust toxicity has to be evaluated in view of future manned missions to the
      Moon. Previous studies on lunar specimens and simulated dusts have revealed an
      oxidant activity assigned to HO. release. However, the mechanisms behind the
      reactivity of lunar dust are still quite unclear at the molecular level. In the
      present study, a complementary set of tests--including terephthalate (TA)
      hydroxylation, free radical release as measured by means of the spin
      trapping/electron paramagnetic resonance (EPR) technique, and cell-free
      lipoperoxidation--is proposed to investigate the reactions induced by the fine
      fraction of a lunar dust analogue (JSC-1A-vf) in biologically relevant
      experimental environments. Our study proved that JSC-1A-vf is able to hydroxylate
      TA also in anaerobic conditions, which indicates that molecular oxygen is not
      involved in such a reaction. Spin-trapping/EPR measures showed that the HO.
      radical is not the reactive intermediate involved in the oxidative potential of
      JSC-1A-vf. A surface reactivity implying a redox cycle of phosphate-complexed
      iron via a Fe(IV) state is proposed. The role of this iron species was
      investigated by assessing the reactivity of JSC-1A-vf toward hydrogen peroxide
      (Fenton-like activity), formate ions (homolytic rupture of C-H bond), and
      linoleic acid (cell-free lipoperoxidation). JSC-1A-vf was active in all tests,
      confirming that redox centers of transition metal ions on the surface of the dust
      may be responsible for dust reactivity and that the TA assay may be a useful
      field probe to monitor the surface oxidative potential of lunar dust.

PMID- 25946078
TI  - Sirtuins and proteolytic systems: implications for pathogenesis of
      synucleinopathies.
AB  - Insoluble and fibrillar forms of alpha-synuclein are the major components of Lewy
      bodies, a hallmark of several sporadic and inherited neurodegenerative diseases
      known as synucleinopathies. alpha-Synuclein is a natural unfolded and aggregation
      prone protein that can be degraded by the ubiquitin-proteasomal system and the
      lysosomal degradation pathways. alpha-Synuclein is a target of the main cellular
      proteolytic systems, but it is also able to alter their function further,
      contributing to the progression of neurodegeneration. Aging, a major risk for
      synucleinopathies, is associated with a decrease activity of the proteolytic
      systems, further aggravating this toxic looping cycle. Here, the current
      literature on the basic aspects of the routes for alpha-synuclein clearance, as
      well as the consequences of the proteolytic systems collapse, will be discussed.
      Finally, particular focus will be given to the sirtuins's role on proteostasis
      regulation, since their modulation emerged as a promising therapeutic strategy to
      rescue cells from alpha-synuclein toxicity. The controversial reports on the
      potential role of sirtuins in the degradation of alpha-synuclein will be
      discussed. Connection between sirtuins and proteolytic systems is definitely
      worth of further studies to increase the knowledge that will allow its proper
      exploration as new avenue to fight synucleinopathies. 

PMID- 25946082
TI  - Fluorescence guided resection and glioblastoma in 2015: A review.
AB  - High-grade gliomas represent a widely heterogeneous group of tumors, the most
      frequent of which is glioblastoma multiforme. Its annual incidence has risen over
      the last decades, particularly amongst elderly people. The actual standards of
      care allow for a 15-month median survival rate for WHO grade IV gliomas. As
      recurrence occurs in more than 85% of patients at the surgical margins, the
      initial resection extent is a cornerstone of disease control. Fluorescence guided
      resection (FGR) aims at increasing complete resections and, thus, local control.
      This technique uses 5-aminolevulinic acid (5-ALA), a natural intermediate
      substance in the heme-porphyrin biosynthesis pathway, and a protoporphyrin IX
      (PpIX) precursor. PpIX is fluorescent under blue light exposure. Recent studies
      reported a significant increase in complete resections using FGR, which were
      associated with prolonged progression free survival, fewer reinterventions, and
      delayed neurological deterioration. Here, we depict the principles of this
      surgical technique, its actual outcomes, and future developments.

PMID- 25946081
TI  - Sexual Dimorphism in MAPK-Activated Protein Kinase-2 (MK2) Regulation of RANKL
      Induced Osteoclastogenesis in Osteoclast Progenitor Subpopulations.
AB  - Osteoclasts (OCs) are bone-resorptive cells critical for maintaining skeletal
      integrity through coupled bone turnover. OC differentiation and activation
      requires receptor activator of NF-kB ligand (RANKL) signaling through the p38
      MAPK pathway. However the role of the p38 MAPK substrate, MAPK-activated protein
      kinase 2 (MK2), is not clearly delineated. Within the bone marrow exists a
      specific subpopulation of defined osteoclast progenitor cells (dOCPs) with
      surface expression of B220(-)Gr1(-)CD11b(lo/-)CD115(+) (dOCP(lo/-)). In this
      study, we isolated dOCPs from male and female mice to determine sex-specific
      effects of MK2 signaling in osteoclastogenesis (OCgen). Male Mk2(-/-) mice
      display an increase in the dOCP(lo) cell population when compared to Mk2(+/+)
      mice, while female Mk2(-/-) and Mk2(+/+ )mice exhibit no difference. Defined OCPs
      from male and female Mk2(+/+) and Mk2(-/-) bone marrow were treated with
      macrophage colony stimulation factor (M-CSF) and RANKL cytokines to promote
      OCgen. RANKL treatment of dOCP(lo) cells stimulated p38 and MK2 phosphorylation.
      Tartrate-resistant acid phosphatase (TRAP) assays were used to quantify OC
      number, size, and TRAP enzyme activity post-RANKL stimulation. MK2 signaling was
      critical for male dOCP(lo) OCgen, yet MK2 signaling regulated OCgen from female
      dOCP- and CD11b(hi) subpopulations as well. The functional gene, Ctsk, was
      attenuated in both male and female Mk2(-/-) dOCP(lo)-derived OCs. Conversely, MK2
      signaling was only critical for gene expression of pre-OC fusion genes, Oc-stamp
      andTm7sf4, in male OCgen. Therefore, these data suggest there is a sexual
      dimorphism in MK2 signaling of OCP subpopulations.

PMID- 25946083
TI  - Heterogeneous cell-cycle behavior in response to UVB irradiation by a population
      of single cancer cells visualized by time-lapse FUCCI imaging.
AB  - The present study analyzed the heterogeneous cell-cycle dependence and fate of
      single cancer cells in a population treated with UVB using a fluorescence
      ubiquitination-based cell-cycle (FUCCI) imaging system. HeLa cells expressing
      FUCCI were irradiated by 100 or 200 J/m(2) UVB. Modulation of the cell-cycle and
      apoptosis were observed by time-lapse confocal microscopy imaging every 30 min
      for 72 h. Correlation between cell survival and factors including cell-cycle
      phase at the time of the irradiation of UVB, mitosis and the G1/S transition were
      analyzed using the Kaplan-Meier method along with the log rank test. Time-lapse
      FUCCI imaging of HeLa cells demonstrated that UVB irradiation induced cell-cycle
      arrest in S/G2/M phase in the majority of the cells. The cells irradiated by 100
      or 200 J/m(2) UVB during G0/G1 phase had a higher survival rate than the cells
      irradiated during S/G2/M phase. A minority of cells could escape S/G2/M arrest
      and undergo mitosis which significantly correlated with decreased survival of the
      cells. In contrast, G1/S transition significantly correlated with increased
      survival of the cells after UVB irradiation. UVB at 200 J/m(2) resulted in a
      greater number of apoptotic cells.

PMID- 25946084
TI  - Vitamin D for the treatment of chronic painful conditions in adults.
AB  - BACKGROUND: This review is an update of a previously published review in the
      Cochrane Database of Systematic Reviews (Issue 1, 2010) on 'Vitamin D for the
      treatment of chronic painful conditions in adults'.Vitamin D is produced in the
      skin after exposure to sunlight and can be obtained through food. Vitamin D
      deficiency has been linked with a range of conditions, including chronic pain.
      Observational and circumstantial evidence suggests that there may be a role for
      vitamin D deficiency in the aetiology of chronic painful conditions. OBJECTIVES:
      To assess the efficacy and safety of vitamin D supplementation in chronic painful
      conditions when tested against placebo or against active comparators. SEARCH
      METHODS: For this update, we searched the Cochrane Central Register of Controlled
      Trials (CENTRAL), MEDLINE, and EMBASE to February 2015. This was supplemented by
      searching the reference lists of retrieved articles, reviews in the field, and
      online trial registries. SELECTION CRITERIA: We included studies if they were
      randomised double-blind trials of vitamin D supplementation compared with placebo
      or with active comparators for the treatment of chronic painful conditions in
      adults. DATA COLLECTION AND ANALYSIS: Two review authors independently selected
      the studies for inclusion, assessed methodological quality, and extracted data.
      We did not undertake pooled analysis due to the heterogeneity of the data.
      Primary outcomes of interest were pain responder outcomes, and secondary outcomes
      were treatment group average pain outcomes and adverse events. MAIN RESULTS: We
      included six new studies (517 participants) in this review update, bringing the
      total of included studies to 10 (811 participants). The studies were
      heterogeneous with regard to study quality, the chronic painful conditions that
      were investigated, the dose of vitamin D given, co-interventions, and the outcome
      measures reported. Only two studies reported responder pain outcomes; the other
      studies reported treatment group average outcomes only. Overall, there was no
      consistent pattern that vitamin D treatment was associated with greater efficacy
      than placebo in any chronic painful condition (low quality evidence). Adverse
      events and withdrawals were comparatively infrequent, with no consistent
      difference between vitamin D and placebo (good quality evidence). AUTHORS'
      CONCLUSIONS: The evidence addressing the use of vitamin D for chronic pain now
      contains more than twice as many studies and participants than were included in
      the original version of this review. Based on this evidence, a large beneficial
      effect of vitamin D across different chronic painful conditions is unlikely.
      Whether vitamin D can have beneficial effects in specific chronic painful
      conditions needs further investigation.

PMID- 25946085
TI  - A comparison of two methods for quantifying soil organic carbon of alpine
      grasslands on the Tibetan Plateau.
AB  - As CO2 concentrations continue to rise and drive global climate change, much
      effort has been put into estimating soil carbon (C) stocks and dynamics over
      time. However, the inconsistent methods employed by researchers hamper the
      comparability of such works, creating a pressing need to standardize the methods
      for soil organic C (SOC) quantification by the various methods. Here, we
      collected 712 soil samples from 36 sites of alpine grasslands on the Tibetan
      Plateau covering different soil depths and vegetation and soil types. We used an
      elemental analyzer for soil total C (STC) and an inorganic carbon analyzer for
      soil inorganic C (SIC), and then defined the difference between STC and SIC as
      SOCCNS. In addition, we employed the modified Walkley-Black (MWB) method,
      hereafter SOCMWB. Our results showed that there was a strong correlation between
      SOCCNS and SOCMWB across the data set, given the application of a correction
      factor of 1.103. Soil depth and soil type significantly influenced on the
      recovery, defined as the ratio of SOCMWB to SOCCNS, and the recovery was closely
      associated with soil carbonate content and pH value as well. The differences of
      recovery between alpine meadow and steppe were largely driven by soil pH. In
      addition, statistically, a relatively strong correlation between SOCCNS and STC
      was also found, suggesting that it is feasible to estimate SOCCNS stocks through
      the STC data across the Tibetan grasslands. Therefore, our results suggest that
      in order to accurately estimate the absolute SOC stocks and its change in the
      Tibetan alpine grasslands, adequate correction of the modified WB measurements is
      essential with correct consideration of the effects of soil types, vegetation,
      soil pH and soil depth. 

PMID- 25946086
TI  - Ru(II)-Catalyzed Site-Selective Hydroxylation of Flavone and Chromone
      Derivatives: The Importance of the 5-Hydroxyl Motif for the Inhibition of Aurora
      Kinases.
AB  - An efficient protocol for Ru(II)-catalyzed direct C-H oxygenation of a broad
      range of flavone and chromone substrates was developed. This convenient and
      powerful synthetic tool allows for the rapid installation of the hydroxyl group
      into the flavone, chromone, and other related scaffolds and opens the way for
      analog synthesis of highly potent Aurora kinase inhibitors. The molecular docking
      simulations indicate that the formation of bidentate H-bonding patterns in the
      hinge regions between the 5-hydroxyflavonoids and Ala213 was the significant
      binding force, which is consistent with experimental and computational findings. 

PMID- 25946087
TI  - An Autopsy Case of a Pregnant Woman With Severe Placental and Fetal Damage From
      Domestic Violence.
AB  - We present an autopsy case of a pregnant woman who was a victim of domestic
      violence. The deceased showed injuries mainly to her head and abdomen. Postmortem
      examination revealed 1400 mL of abdominal hemorrhage, ablation of the
      perimetrium, placental avulsion, and intracranial hematoma. The cause of death
      was diagnosed as hemorrhagic shock. The uterus contained a fetus of 7 months'
      gestational age. Fetal autopsy revealed laceration of the lungs, laceration and
      avulsion of the liver, and 15 mL of hemoperitoneum. Both placental and fetal
      injuries suggested repeated severe attacks to the abdomen, such as those expected
      to result from kicking or hitting. 

PMID- 25946088
TI  - Correlation between the Lactate Dehydrogenase Levels with Laboratory Variables in
      the Clinical Severity of Sickle Cell Anemia in Congolese Patients.
AB  - BACKGROUND: Sickle cell anemia is an inflammatory disease and is characterized by
      chronic hemolysis. We sought to evaluate the association of lactate dehydrogenase
      levels with specific clinical phenotypes and laboratory variables in patients
      with sickle cell anemia. METHODS: The present cross-sectional study was conducted
      in Sickle Cell Centre of Yolo in Kinshasa, the Democratic Republic of Congo. Two
      hundred and eleven patients with Sickle Cell Anemia in steady state were
      recruited. Seventy-four participants with normal Hb (Hb-AA) were selected as a
      control group. RESULTS: The average rates of hemoglobin, hematocrit, and red
      blood cells tended to be significantly lower in subjects with Hb-SS (p<0.001).
      The average rates of white blood cells, platelets, reticulocytes and serum LDH
      were significantly higher in subjects with Hb-SS (p<0.001). The average rates of
      Hb, HbF, hematocrit and red blood cells of Hb-SS patients with asymptomatic
      clinical phenotype were significantly higher than those of the two other
      phenotypes. However, the average rates of white blood cells, platelets,
      reticulocytes, and LDH of Hb-SS patients with the severe clinical phenotype are
      higher than those of two other clinical phenotypes. Significant correlations were
      observed between Hb and white blood cell in severe clinical phenotype (r3 = -0.37
      *) between Hb and red blood cells in the three phenotypes (r1 = 0.69 * r2 * =
      0.69, r3 = 0.83 *), and finally between Hb and reticulocytes in the asymptomatic
      clinical phenotype and severe clinical phenotype (r1 = -0.50 * r3 = 0.45 *). A
      significant increase in LDH was observed in patients with leg ulcer,
      cholelithiasis and aseptic necrosis of the femoral head. CONCLUSION: The increase
      in serum LDH is accompanied by changes in hematological parameters. In our midst,
      serum LDH may be considered as an indicator of the severity of the disease.

PMID- 25946090
TI  - Forgive and Forget: Differences between Decisional and Emotional Forgiveness.
AB  - To forgive and forget is a well-known idiom, which has rarely been looked at
      empirically. In the current experiment, we investigated differences between
      emotional and decisional forgiveness on forgetting. The present study provides
      the first empirical support that emotional forgiveness has a strong influence on
      subsequent incidental forgetting. Specifically, our results demonstrate that
      emotional forgiveness leads to substantially higher levels of forgetting in
      respect to offense relevant traits compared to both decisional forgiveness and no
      forgiveness. This provides evidence for our hypothesized effect that only
      individuals who have emotionally forgiven a transgression, and not those who just
      decided to forgive, subsequently forget offense relevant traits attributed to the
      transgressor.

PMID- 25946089
TI  - Failure of intravenous or intracardiac delivery of mesenchymal stromal cells to
      improve outcomes after focal traumatic brain injury in the female rat.
AB  - Mesenchymal stromal cells secrete a variety of anti-inflammatory factors and may
      provide a regenerative medicine option for the treatment of traumatic brain
      injury. The present study investigates the efficacy of multiple intravenous or
      intracardiac administrations of rat mesenchymal stromal cells or human
      mesenchymal stromal cells in female rats after controlled cortical impact by in
      vivo MRI, neurobehavior, and histopathology evaluation. Neither intravenous nor
      intracardiac administration of mesenchymal stromal cells derived from either rats
      or humans improved MRI measures of lesion volume or neurobehavioral outcome
      compared to saline treatment. Few mesenchymal stromal cells (<0.0005% of injected
      dose) were found within 3 days of last dosage at the site of injury after either
      delivery route, with no mesenchymal stromal cells being detectable in brain at 30
      or 56 days post-injury. These findings suggest that non-autologous mesenchymal
      stromal cells therapy via intravenous or intracardiac administration is not a
      promising treatment after focal contusion traumatic brain injury in this female
      rodent model. 

PMID- 25946092
TI  - The 41st Annual Meeting of the North American Neuro-Ophthalmology Society.

PMID- 25946091
TI  - Insulin and Leptin Signaling Interact in the Mouse Kiss1 Neuron during the
      Peripubertal Period.
AB  - Reproduction requires adequate energy stores for parents and offspring to
      survive. Kiss1 neurons, which are essential for fertility, have the potential to
      serve as the central sensors of metabolic factors that signal to the reproductive
      axis the presence of stored calories. Paradoxically, obesity is often accompanied
      by infertility. Despite excess circulating levels of insulin and leptin, obese
      individuals exhibit resistance to both metabolic factors in many neuron types.
      Thus, resistance to insulin or leptin in Kiss1 neurons could lead to infertility.
      Single deletion of the receptors for either insulin or the adipokine leptin from
      Kiss1 neurons does not impair adult reproductive dysfunction. However, insulin
      and leptin signaling pathways may interact in such a way as to obscure their
      individual functions. We hypothesized that in the presence of genetic or obesity
      induced concurrent insulin and leptin resistance, Kiss1 neurons would be unable
      to maintain reproductive function. We therefore induced a chronic
      hyperinsulinemic and hyperleptinemic state in mice lacking insulin receptors in
      Kiss1 neurons through high fat feeding and examined the impact on fertility. In
      an additional, genetic model, we ablated both leptin and insulin signaling in
      Kiss1 neurons (IR/LepRKiss mice). Counter to our hypothesis, we found that the
      addition of leptin insensitivity did not alter the reproductive phenotype of
      IRKiss mice. We also found that weight gain, body composition, glucose and
      insulin tolerance were normal in mice of both genders. Nonetheless, leptin and
      insulin receptor deletion altered pubertal timing as well as LH and FSH levels in
      mid-puberty in a reciprocal manner. Our results confirm that Kiss1 neurons do not
      directly mediate the critical role that insulin and leptin play in reproduction.
      However, during puberty kisspeptin neurons may experience a critical window of
      susceptibility to the influence of metabolic factors that can modify the onset of
      fertility. 

PMID- 25946094
TI  - Development of Fluorescence Sensing Material Based on CdSe/ZnS Quantum Dots and
      Molecularly Imprinted Polymer for the Detection of Carbaryl in Rice and Chinese
      Cabbage.
AB  - A fluorescence sensing material based on quantum dots with excellent optical
      properties and molecularly imprinted polymer (QDs@MIP) with specific recognition
      has been developed. First the surface of CdSe/ZnS QDs was modified with ionic
      liquids (ILs) by electrostatic interaction. The fluorescence sensing material was
      constructed from anchoring the MIP layer on IL modified CdSe/ZnS QDs by
      copolymerization, which had been developed for the detection of carbaryl in rice
      and Chinese cabbage. The MIP fluorescence was more strongly quenched by carbaryl
      than the non-imprinted polymer (NIP) fluorescence, which indicated that the
      QDs@MIP could selectively recognize the corresponding carbaryl. Furthermore, the
      developed QDs@MIP method was validated by HPLC and ELISA respectively, and the
      results of these methods were well correlated (R(2) = 0.98). The fluorescence
      sensing material had obvious advantages, such as being easily prepared and having
      specific recognition and photostability. The developed method was simple and
      effective for the detection of carbaryl. And, it could also provide the technical
      support for the rapid detection in food safety fields. 

PMID- 25946093
TI  - Effects of 39 Compounds on Calmodulin-Regulated Adenylyl Cyclases AC1 and
      Bacillus anthracis Edema Factor.
AB  - Adenylyl cyclases (ACs) catalyze the conversion of ATP into the second messenger
      cAMP. Membranous AC1 (AC1) is involved in processes of memory and learning and in
      muscle pain. The AC toxin edema factor (EF) of Bacillus anthracis is involved in
      the development of anthrax. Both ACs are stimulated by the eukaryotic Ca(2+)
      sensor calmodulin (CaM). The CaM-AC interaction could constitute a potential
      target to enhance or impair the AC activity of AC1 and EF to intervene in above
      (patho)physiological mechanisms. Thus, we analyzed the impact of 39 compounds
      including typical CaM-inhibitors, an anticonvulsant, an anticholinergic,
      antidepressants, antipsychotics and Ca(2+)-antagonists on CaM-stimulated
      catalytic activity of AC1 and EF. Compounds were tested at 10 MUM, i.e., a
      concentration that can be reached therapeutically for certain antidepressants and
      antipsychotics. Calmidazolium chloride decreased CaM-stimulated AC1 activity
      moderately by about 30%. In contrast, CaM-stimulated EF activity was abrogated by
      calmidazolium chloride and additionally decreased by chlorpromazine, felodipine,
      penfluridol and trifluoperazine by about 20-40%. The activity of both ACs was
      decreased by calmidazolium chloride in the presence and absence of CaM. Thus, CaM
      stimulated AC1 activity is more insensitive to inhibition by small molecules than
      CaM-stimulated EF activity. Inhibition of AC1 and EF by calmidazolium chloride is
      largely mediated via a CaM-independent allosteric mechanism.

PMID- 25946095
TI  - Isolation and Seroprevalence of Aeromonas spp. Among Common Food Animals
      Slaughtered in Nagpur, Central India.
AB  - Aeromonads are ubiquitous foodborne pathogens with a global distribution. Animal
      origin foods and contaminated animals are the main sources of Aeromonas infection
      to humans. So far little is known about the occurrence of Aeromonas spp. in food
      producing animals in India. The present study was conducted to determine the
      prevalence and seroprevalence of Aeromonas species from 50 each of meat, blood,
      and sera samples collected from cattle, buffaloes, goats, and pigs slaughtered in
      and around Nagpur, Central India. Alkaline peptone water and ampicillin dextrin
      agar were used to isolate Aeromonas spp. An indirect enzyme-linked immunosorbent
      assay (ELISA) was standardized by use of whole-cell antigen (WC) and outer
      membrane protein (OMP) of Aeromonas hydrophila (MTCC 646). Aeromonads were
      isolated from 44 (22%) of the meat samples, and 1 (0.5%) from the blood samples.
      Seroprevalence by indirect ELISA-based WC antigen was estimated as 68% in cattle,
      44% in buffaloes, 60% in goats, and 30% in pigs. OMP-based ELISA yielded a
      seroprevalence of 56%, 48%, 52%, and 22% in cattle, buffaloes, goats, and pigs,
      respectively. The results revealed that OMP-based ELISA and WC-based ELISA were
      in agreement with one another. Isolation along with high seropositivity
      demonstrates the presence of foodborne Aeromonas spp. in the Nagpur city of
      Central India. 

PMID- 25946096
TI  - What limits contact lens comfort? Let's see.

PMID- 25946098
TI  - Vision, training hours, and road testing results in bioptic drivers.
AB  - PURPOSE: Bioptic telescopic spectacles can be used by people with central visual
      acuity that does not meet the state standards to obtain an unrestricted driver's
      license. The purpose of this study was to examine the relationships among visual
      and demographic factors, training hours, and the results of road testing for
      bioptic drivers. METHODS: A retrospective study of patients who received an
      initial daylight bioptic examination at the Ohio State University and
      subsequently received a bioptic license was conducted. Data were collected on
      vision including visual acuity, contrast sensitivity, and visual field. Hours of
      driver training and results of Highway Patrol road testing were extracted from
      records. Relationships among vision, training hours, and road testing were
      analyzed. RESULTS: Ninety-seven patients who completed a vision examination
      between 2004 and 2008 and received daylight licensure with bioptic telescopic
      spectacles were included. Results of the first Highway Patrol road test were
      available for 74 patients. The median (interquartile range) hours of training
      before road testing was 21 (17) hours (range, 9 to 75 hours). Candidates without
      previous licensure were younger (p < 0.001) and had more documented training (p <
      0.001). Lack of previous licensure and more training were significantly
      associated with having failed a portion of the Highway Patrol test and points
      deducted on the road test. CONCLUSIONS: New bioptic drivers without previous
      nonbioptic driving experience required more training and performed more poorly on
      road testing for licensure than those who had previous nonbioptic licensure. No
      visual factor was predictive of road testing results after adjustment for
      previous experience. The hours of training received remained predictive of road
      testing outcome even with adjustment for previous experience. These results
      suggest that previous experience and trainer assessments should be investigated
      as potential predictors of road safety in bioptic drivers in future studies.

PMID- 25946099
TI  - Does correcting astigmatism with toric lenses improve driving performance?
AB  - PURPOSE: Driving is a vision-based activity of daily living that impacts safety.
      Because visual disruption can compromise driving safety, contact lens wearers
      with astigmatism may pose a driving safety risk if they experience residual blur
      from spherical lenses that do not correct their astigmatism or if they experience
      blur from toric lenses that rotate excessively. Given that toric lens
      stabilization systems are continually improving, this preliminary study tested
      the hypothesis that astigmats wearing toric contact lenses, compared with
      spherical lenses, would exhibit better overall driving performance and driving
      specific visual abilities. METHODS: A within-subject, single-blind, crossover,
      randomized design was used to evaluate driving performance in 11 young adults
      with astigmatism (-0.75 to -1.75 diopters cylinder). Each participant drove a
      highly immersive, virtual reality driving simulator (210 degrees field of view)
      with (1) no correction, (2) spherical contact lens correction (ACUVUE MOIST), and
      (3) toric contact lens correction (ACUVUE MOIST for Astigmatism). Tactical
      driving skills such as steering, speed management, and braking, as well as
      operational driving abilities such as visual acuity, contrast sensitivity, and
      foot and arm reaction time, were quantified. RESULTS: There was a main effect for
      type of correction on driving performance (p = 0.05). Correction with toric
      lenses resulted in significantly safer tactical driving performance than no
      correction (p < 0.05), whereas correction with spherical lenses did not differ in
      driving safety from no correction (p = 0.118). Operational tests differentiated
      corrected from uncorrected performance for both spherical (p = 0.008) and toric
      (p = 0.011) lenses, but they were not sensitive enough to differentiate toric
      from spherical lens conditions. CONCLUSIONS: Given previous research showing that
      deficits in these tactical skills are predictive of future real-world collisions,
      these preliminary data suggest that correcting low to moderate astigmatism with
      toric lenses may be important to driving safety. Their merits relative to
      spherical lens correction require further investigation.

PMID- 25946100
TI  - Random word recognition chart helps scotoma assessment in low vision.
AB  - PURPOSE: To evaluate the use of SKread, a vision test based on random word
      sequences that prevents the prediction of upcoming words by linguistic criteria
      and is simple to score in a clinical setting. METHODS: SKread combines the
      standardized format of the MNread test with sequences of random words and letters
      like the Pepper Visual Skills for Reading test. A total of 231 subjects (aged 16
      to 97 years) participated. We report data from 136 eyes of subjects with a
      maculopathy and 65 with normal or near-normal vision. Test reliability was
      investigated on an additional 30 eye-healthy subjects. We tested visual acuity
      and reading performance for continuous text and random words monocularly. Reading
      speed and all errors made are reported. RESULTS: Reading speed was always higher
      for continuous text than for random word sequences, even in normally sighted
      subjects for whom the median reading times per paragraph were 2.4 s (MNread) vs.
      6.8 s (SKread). In patients with maculopathies, the medians were 4.2 s vs. 12.25
      s. These differences were statistically significant. Number and type of errors
      made depended only negligibly on age and visual acuity. Patients with a dense
      scotoma right of fixation made more "right errors" by missing letters at the end
      of words, whereas those with a scotoma left of fixation made more "left errors"
      by missing letters at the beginning of words. The SKread test showed good test
      retest repeatability. CONCLUSIONS: The unpredictability of random word and letter
      sequences renders reading performance highly dependent on eyesight and less
      dependent on reading skill and educational level. Recurrent right or left errors
      can indicate the presence and location of a scotoma without expensive equipment.
      This knowledge can be used to teach patients about how the scotoma can interfere
      with their vision.

PMID- 25946104
TI  - 'You never leave work when you live on a cattle property': Special problems for
      rural property owners who have to relocate for specialist treatment.
AB  - OBJECTIVE: This paper contributes to the literature on relocation for specialist
      care by providing findings on specific issues impacting on rural farmers and
      property owners who have to travel to the metropolitan area for specialist care
      for a haematological malignancy. DESIGN AND SETTING: This paper uses descriptive
      qualitative research based on 45 interviews with patients with haematology in
      Queensland. The interviews were audio-recorded, transcribed verbatim, coded and
      thematically analysed. RESULTS: In addition to issues of distance, farmers and
      rural property owners who have to relocate for specialist care must deal with
      problems associated with the lack of opportunity to take absence from the
      property because of the inescapable pressure of daily farm and property
      responsibilities and the high cost of, or lack of opportunity to, outsource daily
      maintenance. Further concerns include the cost of relocation in the context of
      continuing drought, serious problems sustaining the travel and time away
      required, and the lack of choice for some but to deal with treatment alone.
      CONCLUSION: In recent years there has been considerable progress with regard to
      overcoming the distance barrier for rural and remote patients with cancer through
      innovative clinical models using technology and telemedicine. However, there has
      been limited uptake of such models for patients with haematology. The present
      findings indicate that from the perspective of rural farmers and property owners
      there are important reasons why the use of innovative strategies should be
      fostered and expanded.

PMID- 25946103
TI  - CD8+ T Cell Fate and Function Influenced by Antigen-Specific Virus-Like
      Nanoparticles Co-Expressing Membrane Tethered IL-2.
AB  - A variety of adjuvants fostering humoral immunity are known as of today. However,
      there is a lack of adjuvants or adjuvant strategies, which directly target T
      cellular effector functions and memory. We here determined whether systemically
      toxic cytokines such as IL-2 can be restricted to the site of antigen
      presentation and used as 'natural adjuvants'. Therefore, we devised antigen
      presenting virus-like nanoparticles (VNP) co-expressing IL-2 attached to
      different membrane-anchors and assessed their potency to modulate CD8+ T cell
      responses in vitro and in vivo. Efficient targeting of IL-2 to lipid rafts and
      ultimately VNP was achieved by fusing IL-2 at its C-terminus to a minimal
      glycosylphosphatidylinositol (GPI)-anchor acceptor sequence. To identify optimal
      membrane-anchor dimensions we inserted one (1Ig), two (2Ig) or four (4Ig)
      immunoglobulin(Ig)-like domains of CD16b between IL-2 and the minimal GPI-anchor
      acceptor sequence of CD16b (GPI). We found that the 2IgGPI version was superior
      to all other evaluated IL-2 variants (IL-2v) in terms of its i) degree of
      targeting to lipid rafts and to the VNP surface, ii) biological activity, iii) co
      stimulation of cognate T cells in the absence of bystander activation and iv)
      potency to induce differentiation and acquisition of CD8+ T cell effector
      functions in vitro and in vivo. In contrast, the GPI version rather favored
      memory precursor cell formation. These results exemplify novel beneficial
      features of membrane-bound IL-2, which in addition to its mere T cell stimulatory
      capacity include the induction of differential effector and memory functions in
      CD8+ T lymphocytes. 

PMID- 25946105
TI  - Identification of CTLA2A, DEFB29, WFDC15B, SERPINA1F and MUP19 as Novel Tissue
      Specific Secretory Factors in Mouse.
AB  - Secretory factors in animals play an important role in communication between
      different cells, tissues and organs. Especially, the secretory factors with
      specific expression in one tissue may reflect important functions and unique
      status of that tissue in an organism. In this study, we identified potential
      tissue-specific secretory factors in the fat, muscle, heart, lung, kidney and
      liver in the mouse by analyzing microarray data from NCBI's Gene Expression
      Omnibus (GEO) public repository and searching and predicting their subcellular
      location in GeneCards and WoLF PSORT, and then confirmed tissue-specific
      expression of the genes using semi-quantitative PCR reactions. With this
      approach, we confirmed 11 lung, 7 liver, 2 heart, 1 heart and muscle, 7 kidney
      and 2 adipose and liver-specific secretory factors. Among these genes, 1 lung
      specific gene--CTLA2A (cytotoxic T lymphocyte-associated protein 2 alpha), 3
      kidney-specific genes--SERPINA1F (serpin peptidase inhibitor, Clade A, member
      1F), WFDC15B (WAP four-disulfide core domain 15B) and DEFB29 (defensin beta 29)
      and 1 liver-specific gene--MUP19 (major urinary protein 19) have not been
      reported as secretory factors. These genes were tagged with hemagglutinin at the
      3'end and then transiently transfected to HEK293 cells. Through protein detection
      in cell lysate and media using Western blotting, we verified secretion of the 5
      genes and predicted the potential pathways in which they may participate in the
      specific tissue through data analysis of GEO profiles. In addition, alternative
      splicing was detected in transcripts of CTLA2A and SERPINA1F and the
      corresponding proteins were found not to be secreted in cell culture media.
      Identification of novel secretory factors through the current study provides a
      new platform to explore novel secretory factors and a general direction for
      further study of these genes in the future.

PMID- 25946106
TI  - Predicting protein-protein interactions from primary protein sequences using a
      novel multi-scale local feature representation scheme and the random forest.
AB  - The study of protein-protein interactions (PPIs) can be very important for the
      understanding of biological cellular functions. However, detecting PPIs in the
      laboratories are both time-consuming and expensive. For this reason, there has
      been much recent effort to develop techniques for computational prediction of
      PPIs as this can complement laboratory procedures and provide an inexpensive way
      of predicting the most likely set of interactions at the entire proteome scale.
      Although much progress has already been achieved in this direction, the problem
      is still far from being solved. More effective approaches are still required to
      overcome the limitations of the current ones. In this study, a novel Multi-scale
      Local Descriptor (MLD) feature representation scheme is proposed to extract
      features from a protein sequence. This scheme can capture multi-scale local
      information by varying the length of protein-sequence segments. Based on the MLD,
      an ensemble learning method, the Random Forest (RF) method, is used as
      classifier. The MLD feature representation scheme facilitates the mining of
      interaction information from multi-scale continuous amino acid segments, making
      it easier to capture multiple overlapping continuous binding patterns within a
      protein sequence. When the proposed method is tested with the PPI data of
      Saccharomyces cerevisiae, it achieves a prediction accuracy of 94.72% with 94.34%
      sensitivity at the precision of 98.91%. Extensive experiments are performed to
      compare our method with existing sequence-based method. Experimental results show
      that the performance of our predictor is better than several other state-of-the
      art predictors also with the H. pylori dataset. The reason why such good results
      are achieved can largely be credited to the learning capabilities of the RF model
      and the novel MLD feature representation scheme. The experiment results show that
      the proposed approach can be very promising for predicting PPIs and can be a
      useful tool for future proteomic studies.

PMID- 25946107
TI  - What is the point of pseudokinases?
AB  - The interaction between an active kinase and an 'inactive' pseudokinase provides
      clues about how these enzymes were regulated in the past, and how this regulation
      has evolved. 

PMID- 25946109
TI  - Editorial: showing due DILIgence--the lessons from anabolic steroids; authors'
      reply.

PMID- 25946110
TI  - Decrease in Ribosomal RNA in Candida albicans Induced by Serum Exposure.
AB  - Candida albicans is an important polymorphic human pathogen. It can switch from a
      unicellular yeast form to germinating hypha, which may play a role in making it
      the successful pathogen it is. This hyphal transformation can be triggered by
      various extracellular stimuli, the most potent one being serum from any source.
      We have previously reported that Candida albicans transiently polyadenylates
      portions of both the large and small subunits of ribosomal RNA, shortly after
      serum exposure. Northern blots at the same time suggested that serum might induce
      a decrease in total ribosomal RNA. We have carried out a number of experiments to
      carefully assess this possibility and now report that serum significantly reduces
      ribosomal RNA in Candida albicans. Fluorometric measurements, Northern blotting
      and quantitative RT-PCR, have all confirmed this decrease. Timed experiments show
      that serum induces this decrease rapidly, as it was seen in as early as five
      minutes. Cell mass is not decreased as total cellular protein content remains the
      same and metabolic activity does not appear to slow, as assessed by XTT assay,
      and by the observation that cells form hyphal structures robustly. Another hyphal
      inducer, N-acetylglucosamine, also caused RNA decrease, but to a lesser extent.
      We also observed it in non-germinating yeast, such as Candida glabrata. The
      reason for this decrease is unknown and overall our data suggests that decrease
      in rRNA does not play a causal role in hyphal transformation. Rapid and
      significant decrease in a molecule so central to the yeast's biology is of some
      importance, and further studies, such as its effect on protein metabolism, will
      be required to better understand its purpose. 

PMID- 25946108
TI  - MorphoGraphX: A platform for quantifying morphogenesis in 4D.
AB  - Morphogenesis emerges from complex multiscale interactions between genetic and
      mechanical processes. To understand these processes, the evolution of cell shape,
      proliferation and gene expression must be quantified. This quantification is
      usually performed either in full 3D, which is computationally expensive and
      technically challenging, or on 2D planar projections, which introduces
      geometrical artifacts on highly curved organs. Here we present MorphoGraphX (
      www.MorphoGraphX.org), a software that bridges this gap by working directly with
      curved surface images extracted from 3D data. In addition to traditional 3D image
      analysis, we have developed algorithms to operate on curved surfaces, such as
      cell segmentation, lineage tracking and fluorescence signal quantification. The
      software's modular design makes it easy to include existing libraries, or to
      implement new algorithms. Cell geometries extracted with MorphoGraphX can be
      exported and used as templates for simulation models, providing a powerful
      platform to investigate the interactions between shape, genes and growth.

PMID- 25946111
TI  - Possible esthesioneuroblastoma metastasis to paranasal sinuses: Clinical report
      and literature review.
AB  - BACKGROUND: Local recurrence, and regional and distant metastases, respectively,
      develop in 30% and 15% of patients with esthesioneuroblastoma (ENB). METHODS:
      This case report includes 3 patients with unusual recurrences of ENB in the
      sinonasal tract. RESULTS: Patient 1 developed ENB in the bilateral maxillary
      sinuses after unilateral endoscopic resection of a left ENB followed by
      postoperative proton radiotherapy. Patient 2 developed ENB at the left optic
      carotid recess 7 years after a craniofacial resection and postoperative
      radiotherapy. Patient 3 developed ENB over the left zygomatic process of the
      maxilla 4 years after a cranioendoscopic resection and postoperative radiation
      therapy for ENB of the ethmoid sinuses with intracranial extension. The
      possibility of venous tumor emboli must be considered as a likely etiology.
      However, alternative explanations include the development of a second primary or
      potential transformation because of tumor signaling. CONCLUSION: We present 3
      cases that may represent metastasis of ENB within the sinonasal tract.

PMID- 25946113
TI  - A Prognostic Model for Development of Profound Shock among Children Presenting
      with Dengue Shock Syndrome.
AB  - PURPOSE: To identify risk factors and develop a prediction model for the
      development of profound and recurrent shock amongst children presenting with
      dengue shock syndrome (DSS). METHODS: We analyzed data from a prospective cohort
      of children with DSS recruited at the Paediatric Intensive Care Unit of the
      Hospital for Tropical Disease in Ho Chi Minh City, Vietnam. The primary endpoint
      was "profound DSS", defined as >=2 recurrent shock episodes (for subjects
      presenting in compensated shock), or >=1 recurrent shock episodes (for subjects
      presenting initially with decompensated/hypotensive shock), and/or requirement
      for inotropic support. Recurrent shock was evaluated as a secondary endpoint.
      Risk factors were pre-defined clinical and laboratory variables collected at the
      time of presentation with shock. Prognostic model development was based on
      logistic regression and compared to several alternative approaches. RESULTS: The
      analysis population included 1207 children of whom 222 (18%) progressed to
      "profound DSS" and 433 (36%) had recurrent shock. Independent risk factors for
      both endpoints included younger age, earlier presentation, higher pulse rate,
      higher temperature, higher haematocrit and, for females, worse hemodynamic status
      at presentation. The final prognostic model for "profound DSS" showed acceptable
      discrimination (AUC=0.69 for internal validation) and calibration and is
      presented as a simple score-chart. CONCLUSIONS: Several risk factors for
      development of profound or recurrent shock among children presenting with DSS
      were identified. The score-chart derived from the prognostic models should
      improve triage and management of children presenting with DSS in dengue-endemic
      areas.

PMID- 25946112
TI  - Sequential conformational changes in the morbillivirus attachment protein
      initiate the membrane fusion process.
AB  - Despite large vaccination campaigns, measles virus (MeV) and canine distemper
      virus (CDV) cause major morbidity and mortality in humans and animals,
      respectively. The MeV and CDV cell entry system relies on two interacting
      envelope glycoproteins: the attachment protein (H), consisting of stalk and head
      domains, co-operates with the fusion protein (F) to mediate membrane fusion.
      However, how receptor-binding by the H-protein leads to F-triggering is not fully
      understood. Here, we report that an anti-CDV-H monoclonal antibody (mAb-1347),
      which targets the linear H-stalk segment 126-133, potently inhibits membrane
      fusion without interfering with H receptor-binding or F-interaction. Rather, mAb
      1347 blocked the F-triggering function of H-proteins regardless of the presence
      or absence of the head domains. Remarkably, mAb-1347 binding to headless CDV H,
      as well as standard and engineered bioactive stalk-elongated CDV H-constructs
      treated with cells expressing the SLAM receptor, was enhanced. Despite proper
      cell surface expression, fusion promotion by most H-stalk mutants harboring
      alanine substitutions in the 126-138 "spacer" section was substantially impaired,
      consistent with deficient receptor-induced mAb-1347 binding enhancement. However,
      a previously reported F-triggering defective H-I98A variant still exhibited the
      receptor-induced "head-stalk" rearrangement. Collectively, our data spotlight a
      distinct mechanism for morbillivirus membrane fusion activation: prior to
      receptor contact, at least one of the morbillivirus H-head domains interacts with
      the membrane-distal "spacer" domain in the H-stalk, leaving the F-binding site
      located further membrane-proximal in the stalk fully accessible. This "head-to
      spacer" interaction conformationally stabilizes H in an auto-repressed state,
      which enables intracellular H-stalk/F engagement while preventing the inherent H
      stalk's bioactivity that may prematurely activate F. Receptor-contact disrupts
      the "head-to-spacer" interaction, which subsequently "unlocks" the stalk,
      allowing it to rearrange and trigger F. Overall, our study reveals essential
      mechanistic requirements governing the activation of the morbillivirus membrane
      fusion cascade and spotlights the H-stalk "spacer" microdomain as a possible drug
      target for antiviral therapy. 

PMID- 25946114
TI  - Incorporation of Unnatural Amino Acids in Response to the AGG Codon.
AB  - The biological protein synthesis system has been engineered to incorporate
      unnatural amino acid into proteins, and this has opened up new routes for
      engineering proteins with novel compositions. While such systems have been
      successfully applied in research, there remains a need to develop new approaches
      with respect to the wider application of unnatural amino acids. In this study, we
      reported a strategy for incorporating unnatural amino acids into proteins by
      reassigning one of the Arg sense codons, the AGG codon. Using this method,
      several unnatural amino acids were quantitatively incorporated into the AGG site.
      Furthermore, we applied the method to multiple AGG sites, and even to tandem AGG
      sequences. The method developed and described here could be used for engineering
      proteins with diverse unnatural amino acids, particularly when employed in
      combination with other methods.

PMID- 25946115
TI  - Wind-Mediated Spread of Low-Pathogenic Avian Influenza Virus into the Environment
      during Outbreaks at Commercial Poultry Farms.
AB  - Avian influenza virus-infected poultry can release a large amount of virus
      contaminated droppings that serve as sources of infection for susceptible birds.
      Much research so far has focused on virus spread within flocks. However, as fecal
      material or manure is a major constituent of airborne poultry dust, virus
      contaminated particulate matter from infected flocks may be dispersed into the
      environment. We collected samples of suspended particulate matter, or the
      inhalable dust fraction, inside, upwind and downwind of buildings holding poultry
      infected with low-pathogenic avian influenza virus, and tested them for the
      presence of endotoxins and influenza virus to characterize the potential impact
      of airborne influenza virus transmission during outbreaks at commercial poultry
      farms. Influenza viruses were detected by RT-PCR in filter-rinse fluids collected
      up to 60 meters downwind from the barns, but virus isolation did not yield any
      isolates. Viral loads in the air samples were low and beyond the limit of RT-PCR
      quantification except for one in-barn measurement showing a virus concentration
      of 8.48 x 10(4) genome copies/m(3). Air samples taken outside poultry barns had
      endotoxin concentrations of ~50 EU/m(3) that declined with increasing distance
      from the barn. Atmospheric dispersion modeling of particulate matter, using
      location-specific meteorological data for the sampling days, demonstrated a
      positive correlation between endotoxin measurements and modeled particulate
      matter concentrations, with an R(2) varying from 0.59 to 0.88. Our data suggest
      that areas at high risk for human or animal exposure to airborne influenza
      viruses can be modeled during an outbreak to allow directed interventions
      following targeted surveillance.

PMID- 25946116
TI  - Antiviral Activity of Flexibilane and Tigliane Diterpenoids from Stillingia
      lineata.
AB  - In an effort to identify new potent and selective inhibitors of chikungunya virus
      and HIV-1 and HIV-2 virus replication, the endemic Mascarene species Stillingia
      lineata was investigated. LC/MS and bioassay-guided purification of the EtOAc
      leaf extract using a chikungunya virus-cell-based assay led to the isolation of
      six new (4-9) and three known (1-3) tonantzitlolones possessing the rare C20
      flexibilane skeleton, along with tonantzitloic acid (10), a new linear
      diterpenoid, and three new (11, 13, and 15) and two known (12 and 14) tigliane
      type diterpenoids. The planar structures of the new compounds and their relative
      configurations were determined by spectroscopic analysis, and their absolute
      configurations were determined through comparison with literature data and from
      biogenetic considerations. These compounds were investigated for selective
      antiviral activity against chikungunya virus (CHIKV), Semliki Forest virus,
      Sindbis virus, and, for compounds 11-15, the HIV-1 and HIV-2 viruses. Compounds
      12-15 were found to be the most potent and are selective inhibitors of CHIKV, HIV
      1, and HIV-2 replication. In particular, compound 14 inhibited CHIKV replication
      with an EC50 value of 1.2 MUM on CHIKV and a selectivity index of >240, while
      compound 15 inhibited HIV-1 and HIV-2 with EC50 values of 0.043 and 0.018 MUM,
      respectively. It was demonstrated further that potency and selectivity are
      sensitive to the substitution pattern on the tigliane skeleton. The cytotoxic
      activities of compounds 1-10 were evaluated against the HCT-116, MCF-7, and PC3
      cancer cell lines. 

PMID- 25946117
TI  - Topically Applied Midodrine, 0.2%, an alpha1-Agonist, for the Treatment of
      Erythromelalgia.

PMID- 25946118
TI  - Effect of Rhizobium and arbuscular mycorrhizal fungi inoculation on electrolyte
      leakage in Phaseolus vulgaris roots overexpressing RbohB.
AB  - Respiratory oxidative burst homolog (RBOH)-mediated reactive oxygen species (ROS)
      regulate a wide range of biological functions in plants. They play a critical
      role in the symbiosis between legumes and nitrogen-fixing bacteria or arbuscular
      mycorrhizal (AM) fungi. For instance, overexpression of PvRbohB enhances nodule
      numbers, but reduces mycorrhizal colonization in Phaseolus vulgaris hairy roots
      and downregulation has the opposite effect. In the present study, we assessed the
      effect of both rhizobia and AM fungi on electrolyte leakage in transgenic P.
      vulgaris roots overexpressing (OE) PvRbohB. We demonstrate that elevated levels
      of electrolyte leakage in uninoculated PvRbohB-OE transgenic roots were
      alleviated by either Rhizobium or AM fungi symbiosis, with the latter interaction
      having the greater effect. These results suggest that symbiont colonization
      reduces ROS elevated electrolyte leakage in P. vulgaris root cells. 

PMID- 25946119
TI  - Selective Chemical Labeling of Natural T Modifications in DNA.
AB  - We present a chemical method to selectively tag and enrich thymine modifications,
      5-formyluracil (5-fU) and 5-hydroxymethyluracil (5-hmU), found naturally in DNA.
      Inherent reactivity differences have enabled us to tag 5-fU chemoselectively over
      its C modification counterpart, 5-formylcytosine (5-fC). We rationalized the
      enhanced reactivity of 5-fU compared to 5-fC via ab initio quantum mechanical
      calculations. We exploited this chemical tagging reaction to provide proof of
      concept for the enrichment of 5-fU containing DNA from a pool that contains 5-fC
      or no modification. We further demonstrate that 5-hmU can be chemically oxidized
      to 5-fU, providing a strategy for the enrichment of 5-hmU. These methods will
      enable the mapping of 5-fU and 5-hmU in genomic DNA, to provide insights into
      their functional role and dynamics in biology. 

PMID- 25946120
TI  - Roux-en-Y Gastric Bypass Surgery Induces Early Plasma Metabolomic and Lipidomic
      Alterations in Humans Associated with Diabetes Remission.
AB  - Roux-en-Y gastric bypass (RYGB) is an effective method to attain sustained weight
      loss and diabetes remission. We aimed to elucidate early changes in the plasma
      metabolome and lipidome after RYGB. Plasma samples from 16 insulin-resistant
      morbidly obese subjects, of whom 14 had diabetes, were subjected to global
      metabolomics and lipidomics analysis at pre-surgery and 4 and 42 days after RYGB.
      Metabolites and lipid species were compared between time points and between
      subjects who were in remission and not in remission from diabetes 2 years after
      surgery. We found that the variables that were most discriminatory between time
      points were decanoic acid and octanoic acid, which were elevated 42 days after
      surgery, and sphingomyelins (18:1/21:0 and 18:1/23:3), which were at their lowest
      level 42 days after surgery. Insulin levels were lower at 4 and 42 days after
      surgery compared with pre-surgery levels. At 4 days after surgery, insulin levels
      correlated positively with metabolites of branched chain and aromatic amino acid
      metabolism and negatively with triglycerides with long-chain fatty acids. Of the
      14 subjects with diabetes prior to surgery, 7 were in remission 2 years after
      surgery. The subjects in remission displayed higher pre-surgery levels of
      tricarboxylic acid cycle intermediates and triglycerides with long-chain fatty
      acids compared with subjects not in remission. Thus, metabolic alterations are
      induced soon after surgery and subjects with diabetes remission differ in the
      metabolic profiles at pre- and early post-surgery time points compared to
      patients not in remission. 

PMID- 25946121
TI  - Immunohistochemical expression of cyclin D1 is higher in supratentorial
      ependymomas and predicts relapses in gross total resection cases.
AB  - Ependymomas are tumors of the CNS. Although cyclin D1 overexpression has been
      related to several cancers, its prognostic value in ependymomas has not yet been
      fully established. We evaluated cyclin D1 expression by an immunohistochemistry
      analysis of 149 samples of ependymomas, including some relapses, corresponding to
      121 patients. Eighty-one patients were adults, 60 were intracranial cases and 92
      tumors were grade II. Gross total resection (GTR) was achieved in 62% of cases,
      and relapse was confirmed in 41.4% of cases. Cyclin D1 protein expression was
      analyzed by immunohistochemistry and scored with a labeling index (LI) calculated
      as the percentage of positively stained cells by intensity. We also analyzed
      expression of CCND1 and NOTCH1 in 33 samples of ependymoma by quantitative real
      time PCR. A correlation between cyclin D1 LI score and anaplastic cases (P <
      0.001), supratentorial location (P < 0.001) and age (P = 0.001) were observed. A
      stratified analysis demonstrated that cyclin D1 protein expression was strong in
      tumors with a supratentorial location, independent of the histological grade or
      age. Relapse was more frequent in cases with a higher cyclin D1 LI score (P =
      0.046), and correlation with progression-free survival was observed in cases with
      GTR (P = 0.002). Only spinal canal tumor location and GTR were suggestive markers
      of PFS in multivarite analyses. Higher expression levels were observed in
      anaplastic cases for CCND1 (P = 0.002), in supratentorial cases for CCND1 (P =
      0.008) and NOTCH1 (P = 0.011). There were correlations between the cyclin D1 mRNA
      and protein expression levels (P < 0.0001) and between CCND1 and NOTCH1
      expression levels (P = 0.003). Higher cyclin D1 LI was predominant in
      supratentorial location and predict relapse in GTR cases. Cyclin D1 could be used
      as an immunohistochemical marker to guide follow-up and treatment in these cases.

PMID- 25946123
TI  - A New APEH Cluster with Antioxidant Functions in the Antarctic Hemoglobinless
      Icefish Chionodraco hamatus.
AB  - Acylpeptide hydrolase (APEH) is a ubiquitous cytosolic protease that plays an
      important role in the detoxification of oxidised proteins. In this work, to
      further explore the physiological role of this enzyme, two apeh cDNAs were
      isolated from the Chionodraco hamatus icefish, which lives in the highly
      oxygenated Antarctic marine environment. The encoded proteins (APEH-1(Ch) and
      APEH-2(Ch)) were characterised in comparison with the uniquely expressed isoform
      from the temperate fish Dicentrarchus labrax (APEH-1Dl) and the two APEHs from
      the red-blooded Antarctic fish Trematomus bernacchii (APEH-1(Tb) and APEH-2(Tb)).
      Homology modelling and kinetic characterisation of the APEH isoforms provided new
      insights into their structure/function properties. APEH-2 isoforms were the only
      ones capable of hydrolysing oxidised proteins, with APEH-2(Ch) being more
      efficient than APEH-2(Tb) at this specific function. Therefore, this ability of
      APEH-2 isoforms is the result of an evolutionary adaptation due to the pressure
      of a richly oxygenated environment. The lack of expression of APEH-2 in the
      tissues of the temperate fish used as the controls further supported this
      hypothesis. In addition, analysis of gene expression showed a significant
      discrepancy between the levels of transcripts and those of proteins, especially
      for apeh-2 genes, which suggests the presence of post-transcriptional regulation
      mechanisms, triggered by cold-induced oxidative stress, that produce high basal
      levels of APEH-2 mRNA as a reserve that is ready to use in case of the
      accumulation of oxidised proteins.

PMID- 25946125
TI  - Geographic Distribution of CT, MRI and PET Devices in Japan: A Longitudinal
      Analysis Based on National Census Data.
AB  - BACKGROUND: Japan has the most CT and MRI scanners per unit population in the
      world; however, the geographic distribution of these technologies is currently
      unknown. Moreover, nothing is known of the cause-effect relationship between the
      number of diagnostic imaging devices and their geographic distribution. METHODS:
      Data on the number of CT, MRI and PET devices and that of their utilizations in
      all 1829 municipalities of Japan was generated, based on the Static Survey of
      Medical Institutions conducted by the government. The inter-municipality equity
      of the number of devices or utilizations was evaluated with Gini coefficient.
      RESULTS: Between 2005 and 2011, the number of CT, MRI and PET devices in Japan
      increased by 47% (8789 to 12945), 19% (5034 to 5990) and 70% (274 to 466),
      respectively. Gini coefficient of the number of devices was largest for PET and
      smallest for CT (p for PET-MRI difference <0.001; MRI-CT difference <0.001). For
      all three modalities, Gini coefficient steadily decreased (p for 2011-2005
      difference: <0.001 for CT; 0.003 for MRI; and <0.001 for PET). The number of
      devices in old models (single-detector CT, MRI<1.5 tesla, and conventional PET)
      decreased, while that in new models (multi-detector CT, MRI>=1.5 tesla, and PET
      CT) increased. Gini coefficient of the old models increased or remained unchanged
      (increase rate of 9%, 3%, and -1%; p for 2011-2008 difference <0.001, 0.072, and
      0.562, respectively), while Gini coefficient of the new models decreased (-10%, 
      9%, and -10%; p for 2011-2008 difference <0.001, <0.001, and <0.001
      respectively). Similar results were observed in terms of utilizations.
      CONCLUSIONS: The more abundant a modality, the more equal the modality's
      distribution. Any increase in the modality made its distribution more equal. The
      geographic distribution of the diagnostic imaging technology in Japan appears to
      be affected by spatial competition derived from a market force.

PMID- 25946124
TI  - A General Model of Negative Frequency Dependent Selection Explains Global
      Patterns of Human ABO Polymorphism.
AB  - The ABO locus in humans is characterized by elevated heterozygosity and very
      similar allele frequencies among populations scattered across the globe. Using
      knowledge of ABO protein function, we generated a simple model of asymmetric
      negative frequency dependent selection and genetic drift to explain the
      maintenance of ABO polymorphism and its loss in human populations. In our models,
      regardless of the strength of selection, models with large effective population
      sizes result in ABO allele frequencies that closely match those observed in most
      continental populations. Populations must be moderately small to fall out of
      equilibrium and lose either the A or B allele (N(e) <= 50) and much smaller (N(e)
      <= 25) for the complete loss of diversity, which nearly always involved the
      fixation of the O allele. A pattern of low heterozygosity at the ABO locus where
      loss of polymorphism occurs in our model is consistent with small populations,
      such as Native American populations. This study provides a general evolutionary
      model to explain the observed global patterns of polymorphism at the ABO locus
      and the pattern of allele loss in small populations. Moreover, these results
      inform the range of population sizes associated with the recent human
      colonization of the Americas.

PMID- 25946126
TI  - Oral Microbiota Shift after 12-Week Supplementation with Lactobacillus reuteri
      DSM 17938 and PTA 5289; A Randomized Control Trial.
AB  - BACKGROUND: Lactobacillus spp. potentially contribute to health by modulating
      bacterial biofilm formation, but their effects on the overall oral microbiota
      remain unclear. METHODS AND FINDINGS: Oral microbiota was characterized via 454
      pyrosequencing of the 16S rDNA hypervariable region V3-V4 after 12 weeks of daily
      Lactobacillus reuteri DSM 17938 and PTA 5289 consumption. Forty-four adults were
      assigned to a test group (n = 22) that received lactobacilli lozenges (108 CFU of
      each strain/lozenge) or a control group that received placebo (n = 22). Presence
      of L. reuteri was confirmed by cultivation and species specific PCR. Tooth
      biofilm samples from 16 adults before, during, and after exposure were analyzed
      by pyrosequencing. A total of 1,310,292 sequences were quality filtered. After
      removing single reads, 257 species or phylotypes were identified at 98.5%
      identity in the Human Oral Microbiome Database. Firmicutes, Bacteroidetes,
      Fusobacteria, Proteobacteria, and Actinobacteria were the most abundant phyla.
      Streptococcus was the most common genus and the S. oralis/S. mitis/S. mitis
      bv2/S. infantis group comprised the dominant species. The number of observed
      species was unaffected by L. reuteri exposure. However, subjects who had consumed
      L. reuteri were clustered in a principal coordinates analysis relative to
      scattering at baseline, and multivariate modeling of pyrosequencing microbiota,
      and culture and PCR detected L. reuteri separated baseline from 12-week samples
      in test subjects. L. reuteri intake correlated with increased S. oralis/S.
      mitis/S. mitis bv2/S. infantis group and Campylobacter concisus, Granulicatella
      adiacens, Bergeyella sp. HOT322, Neisseria subflava, and SR1 [G-1] sp. HOT874
      detection and reduced S. mutans, S. anginosus, N. mucosa, Fusobacterium
      periodicum, F. nucleatum ss vincentii, and Prevotella maculosa detection. This
      effect had disappeared 1 month after exposure was terminated. CONCLUSIONS: L.
      reuteri consumption did not affect species richness but induced a shift in the
      oral microbiota composition. The biological relevance of this remains to be
      elucidated. TRIAL REGISTRATION: ClinicalTrials.gov NCT02311218.

PMID- 25946128
TI  - Selective vs Nonselective Nonsteroidal Anti-inflammatory Drugs and Anastomotic
      Leakage After Colorectal Surgery.

PMID- 25946127
TI  - Exploration of the two-photon excitation spectrum of fluorescent dyes at
      wavelengths below the range of the Ti:Sapphire laser.
AB  - We have studied the wavelength dependence of the two-photon excitation efficiency
      for a number of common UV excitable fluorescent dyes; the nuclear stains DAPI,
      Hoechst and SYTOX Green, chitin- and cellulose-staining dye Calcofluor White and
      Alexa Fluor 350, in the visible and near-infrared wavelength range (540-800 nm).
      For several of the dyes, we observe a substantial increase in the fluorescence
      emission intensity for shorter excitation wavelengths than the 680 nm which is
      the shortest wavelength usually available for two-photon microscopy. We also find
      that although the rate of photo-bleaching increases at shorter wavelengths, it is
      still possible to acquire many images with higher fluorescence intensity. This is
      particularly useful for applications where the aim is to image the structure,
      rather than monitoring changes in emission intensity over extended periods of
      time. We measure the excitation spectrum when the dyes are used to stain
      biological specimens to get a more accurate representation of the spectrum of the
      dye in a cell environment as compared to solution-based measurements. 

PMID- 25946129
TI  - Genetic mapping and comparative expression analysis of transcription factors in
      cotton.
AB  - Transcription factors (TFs) play an important role in the regulation of plant
      growth and development. The study of the structure and function of TFs represents
      a research frontier in plant molecular biology. The findings of these studies
      will provide significant information regarding genetic improvement traits in
      crops. Currently, a large number of TFs have been cloned, and their function has
      been verified. However, relatively few studies that genetically map TFs in cotton
      are available. To genetically map TFs in cotton in this study, specific primers
      were designed for TF genes that were published in the Plant Transcription Factor
      Database. A total of 977 TF primers were obtained, and 31 TF polymorphic loci
      were mapped on 15 cotton chromosomes. These polymorphic loci were clearly
      preferentially distributed on chromosomes 5, 11, 19 and 20; and TFs from the same
      family mapped to homologous cotton chromosomes. In-silico mapping verified that
      many mapped TFs were mapped on their corresponding chromosomes or their
      homologous chromosomes' corresponding chromosomes in the diploid genomes. QTL
      mapping for fiber quality revealed that TF-Ghi005602-2 mapped on Chr19 was
      associated with fiber length. Eighty-five TF genes were selected for RT-PCR
      analysis, and 4 TFs were selected for qRT-PCR analysis, revealing unique
      expression patterns across different stages of fiber development between the
      mapping parents. Our data offer an overview of the chromosomal distribution of
      TFs in cotton, and the comparative expression analysis between Gossypium hirsutum
      and G. barbadense provides a rough understanding of the regulation of TFs during
      cotton fiber development. 

PMID- 25946132
TI  - The contribution of mangrove expansion to salt marsh loss on the Texas Gulf
      Coast.
AB  - Landscape-level shifts in plant species distribution and abundance can
      fundamentally change the ecology of an ecosystem. Such shifts are occurring
      within mangrove-marsh ecotones, where over the last few decades, relatively mild
      winters have led to mangrove expansion into areas previously occupied by salt
      marsh plants. On the Texas (USA) coast of the western Gulf of Mexico, most cases
      of mangrove expansion have been documented within specific bays or watersheds.
      Based on this body of relatively small-scale work and broader global patterns of
      mangrove expansion, we hypothesized that there has been a recent regional-level
      displacement of salt marshes by mangroves. We classified Landsat-5 Thematic
      Mapper images using artificial neural networks to quantify black mangrove
      (Avicennia germinans) expansion and salt marsh (Spartina alterniflora and other
      grass and forb species) loss over 20 years across the entire Texas coast. Between
      1990 and 2010, mangrove area grew by 16.1 km(2), a 74% increase. Concurrently,
      salt marsh area decreased by 77.8 km(2), a 24% net loss. Only 6% of that loss was
      attributable to mangrove expansion; most salt marsh was lost due to conversion to
      tidal flats or water, likely a result of relative sea level rise. Our research
      confirmed that mangroves are expanding and, in some instances, displacing salt
      marshes at certain locations. However, this shift is not widespread when analyzed
      at a larger, regional level. Rather, local, relative sea level rise was
      indirectly implicated as another important driver causing regional-level salt
      marsh loss. Climate change is expected to accelerate both sea level rise and
      mangrove expansion; these mechanisms are likely to interact synergistically and
      contribute to salt marsh loss.

PMID- 25946133
TI  - Highly efficient coupling of nanolight emitters to a ultra-wide tunable nanofibre
      cavity.
AB  - Solid-state microcavities combining ultra-small mode volume, wide-range resonance
      frequency tuning, as well as lossless coupling to a single mode fibre are
      integral tools for nanophotonics and quantum networks. We developed an integrated
      system providing all of these three indispensable properties. It consists of a
      nanofibre Bragg cavity (NFBC) with the mode volume of under 1 MUm(3) and
      repeatable tuning capability over more than 20 nm at visible wavelengths. In
      order to demonstrate quantum light-matter interaction, we establish coupling of
      quantum dots to our tunable NFBC and achieve an emission enhancement by a factor
      of 2.7. 

PMID- 25946134
TI  - Rational design of antibiotic treatment plans: a treatment strategy for managing
      evolution and reversing resistance.
AB  - The development of reliable methods for restoring susceptibility after antibiotic
      resistance arises has proven elusive. A greater understanding of the relationship
      between antibiotic administration and the evolution of resistance is key to
      overcoming this challenge. Here we present a data-driven mathematical approach
      for developing antibiotic treatment plans that can reverse the evolution of
      antibiotic resistance determinants. We have generated adaptive landscapes for 16
      genotypes of the TEM beta-lactamase that vary from the wild type genotype "TEM-1"
      through all combinations of four amino acid substitutions. We determined the
      growth rate of each genotype when treated with each of 15 beta-lactam
      antibiotics. By using growth rates as a measure of fitness, we computed the
      probability of each amino acid substitution in each beta-lactam treatment using
      two different models named the Correlated Probability Model (CPM) and the Equal
      Probability Model (EPM). We then performed an exhaustive search through the 15
      treatments for substitution paths leading from each of the 16 genotypes back to
      the wild type TEM-1. We identified optimized treatment paths that returned the
      highest probabilities of selecting for reversions of amino acid substitutions and
      returning TEM to the wild type state. For the CPM model, the optimized
      probabilities ranged between 0.6 and 1.0. For the EPM model, the optimized
      probabilities ranged between 0.38 and 1.0. For cyclical CPM treatment plans in
      which the starting and ending genotype was the wild type, the probabilities were
      between 0.62 and 0.7. Overall this study shows that there is promise for
      reversing the evolution of resistance through antibiotic treatment plans. 

PMID- 25946135
TI  - An Inducible TGF-beta2-TGFbetaR Pathway Modulates the Sensitivity of HNSCC Cells
      to Tyrosine Kinase Inhibitors Targeting Dominant Receptor Tyrosine Kinases.
AB  - The epidermal growth factor receptor (EGFR) is overexpressed in approximately 90%
      of head and neck squamous cell carcinomas (HNSCC), and molecularly targeted
      therapy against the EGFR with the monoclonal antibody cetuximab modestly
      increases overall survival in head and neck cancer patients. We hypothesize that
      co-signaling through additional pathways limits the efficacy of cetuximab and
      EGFR-specific tyrosine kinase inhibitors (TKIs) in the clinical treatment of
      HNSCC. Analysis of gene expression changes in HNSCC cell lines treated 4 days
      with TKIs targeting EGFR and/or fibroblast growth factor receptors (FGFRs)
      identified transforming growth factor beta 2 (TGF-beta2) induction in the three
      cell lines tested. Measurement of TGF-beta2 mRNA validated this observation and
      extended it to additional cell lines. Moreover, TGF-beta2 mRNA was increased in
      primary patient HNSCC xenografts treated for 4 weeks with cetuximab,
      demonstrating in vivo relevance of these findings. Functional genomics analyses
      with shRNA libraries identified TGF-beta2 and TGF-beta receptors (TGFbetaRs) as
      synthetic lethal genes in the context of TKI treatment. Further, direct RNAi
      mediated silencing of TGF-beta2 inhibited cell growth, both alone and in
      combination with TKIs. Also, a pharmacological TGFbetaRI inhibitor similarly
      inhibited basal growth and enhanced TKI efficacy. In summary, the studies support
      a TGF-beta2-TGFbetaR pathway as a TKI-inducible growth pathway in HNSCC that
      limits efficacy of EGFR-specific inhibitors. 

PMID- 25946136
TI  - Let-7 Sensitizes KRAS Mutant Tumor Cells to Chemotherapy.
AB  - KRAS is the most commonly mutated oncogene in human cancers and is associated
      with poor prognosis and drug resistance. Let-7 is a family of tumor suppressor
      microRNAs that are frequently suppressed in solid tumors, where KRAS mutations
      are highly prevalent. In this study, we investigated the potential use of let-7
      as a chemosensitizer. We found that let-7b repletion selectively sensitized KRAS
      mutant tumor cells to the cytotoxicity of paclitaxel and gemcitabine.
      Transfection of let-7b mimic downregulated the expression of mutant but not wild
      type KRAS. Combination of let-7b mimic with paclitaxel or gemcitabine diminished
      MEK/ERK and PI3K/AKT signaling concurrently, triggered the onset of apoptosis,
      and reverted the epithelial-mesenchymal transition in KRAS mutant tumor cells. In
      addition, let-7b repletion downregulated the expression of beta-tubulin III and
      ribonucleotide reductase subunit M2, two proteins known to mediate tumor
      resistance to paclitaxel and gemcitabine, respectively. Let-7 may represent a new
      class of chemosensitizer for the treatment of KRAS mutant tumors. 

PMID- 25946137
TI  - An Efficient Catalytic DNA that Cleaves L-RNA.
AB  - Many DNAzymes have been isolated from synthetic DNA pools to cleave natural RNA
      (D-RNA) substrates and some have been utilized for the design of aptazyme
      biosensors for bioanalytical applications. Even though these biosensors perform
      well in simple sample matrices, they do not function effectively in complex
      biological samples due to ubiquitous RNases that can efficiently cleave D-RNA
      substrates. To overcome this issue, we set out to develop DNAzymes that cleave L
      RNA, the enantiomer of D-RNA, which is known to be completely resistant to
      RNases. Through in vitro selection we isolated three L-RNA-cleaving DNAzymes from
      a random-sequence DNA pool. The most active DNAzyme exhibits a catalytic rate
      constant ~3 min-1 and has a structure that contains a kissing loop, a structural
      motif that has never been observed with D-RNA-cleaving DNAzymes. Furthermore we
      have used this DNAzyme and a well-known ATP-binding DNA aptamer to construct an
      aptazyme sensor and demonstrated that this biosensor can achieve ATP detection in
      biological samples that contain RNases. The current work lays the foundation for
      exploring RNA-cleaving DNAzymes for engineering biosensors that are compatible
      with complex biological samples. 

PMID- 25946138
TI  - Body image change in obese and overweight persons enrolled in weight loss
      intervention programs: a systematic review and meta-analysis.
AB  - To report the results of a systematic review and meta-analysis examining whether
      weight loss interventions improve body image in obese/overweight individuals.
      Medline, Current Contents, and the Cochrane database were searched to identify
      studies involving obese/overweight adults who were enrolled in weight loss
      interventions in which body image was quantitatively assessed. Outcomes assessed
      were changes in body shape concern, body size dissatisfaction, and body
      satisfaction (intervention vs comparator/control group). Seven studies were
      included in the systematic review (4 in the meta-analysis). All but 1 study
      involved female participants only. The type of weight loss intervention varied
      between studies as did the type of control/comparator group. In 3 studies, there
      was no significant difference in body image outcomes, whereas in 4 studies,
      improvement in body image was significantly more pronounced in the intervention
      vs the control/comparator group. Meta-analysis revealed that improvements in body
      shape concern (standardized difference: -0.52; 95% confidence interval [CI]: 
      1.04 to 0.00), body size dissatisfaction (standardized difference: -0.66; 95% CI:
      -0.88 to -0.45), and body satisfaction (standardized difference: 0.74; 95% CI:
      0.09 to 1.38) significantly favored the intervention over the comparator/control
      group (P<0.05). The results of this systematic review/meta-analysis lend support
      to the notion that weight loss interventions may improve body image. This is a
      noteworthy finding that has clear clinical applicability because body image
      affects psychological well-being and the ability of an individual to maintain
      weight loss. Future research should determine which weigh loss interventions are
      associated with optimal improvements in body image and maintenance of weight
      loss. 

PMID- 25946139
TI  - Psoriasis patients' willingness to accept side-effect risks for improved
      treatment efficacy.
AB  - BACKGROUND: Previous studies suggest that efficacy is more important than side
      effect risks to psoriasis patients. However, those studies did not consider
      potentially fatal risks of biologic treatments. OBJECTIVE: To quantify the risks
      patients are willing to accept for improvements in psoriasis symptoms. METHODS:
      Adults with a self-reported physician diagnosis of psoriasis were recruited
      through the National Psoriasis Foundation. Using a discrete-choice experiment,
      patients completed a series of nine choice questions, each including a pair of
      hypothetical treatments. Treatments were defined by severity of plaques, body
      surface area (BSA), and 10-year risks of tuberculosis, serious infection and
      lymphoma. RESULTS: For complete clearance of 25% BSA with mild plaques,
      respondents (n = 1608) were willing to accept a 20% (95% confidence interval: 9
      26%) risk of serious infection, 10% (5-15%) risk of tuberculosis and 2% (1-3%)
      risk of lymphoma. For complete clearance of 25% BSA with severe plaques,
      respondents were willing to accept a 54% (48-62%) risk of serious infection, 36%
      (28-49%) risk of tuberculosis and 8% (7-9%) risk of lymphoma. LIMITATIONS:
      Respondents were asked to evaluate hypothetical scenarios. Actual treatment
      choices may differ. CONCLUSION: Respondents were willing to accept risks above
      likely clinical exposures for improvements in psoriasis symptoms. Individual risk
      tolerances may vary.

PMID- 25946140
TI  - Differentially expressed gene transcripts using RNA sequencing from the blood of
      immunosuppressed kidney allograft recipients.
AB  - We performed RNA sequencing (RNAseq) on peripheral blood mononuclear cells
      (PBMCs) to identify differentially expressed gene transcripts (DEGs) after kidney
      transplantation and after the start of immunosuppressive drugs. RNAseq is
      superior to microarray to determine DEGs because it's not limited to available
      probes, has increased sensitivity, and detects alternative and previously unknown
      transcripts. DEGs were determined in 32 adult kidney recipients, without clinical
      acute rejection (AR), treated with antibody induction, calcineurin inhibitor,
      mycophenolate, with and without steroids. Blood was obtained pre-transplant
      (baseline), week 1, months 3 and 6 post-transplant. PBMCs were isolated, RNA
      extracted and gene expression measured using RNAseq. Principal components (PCs)
      were computed using a surrogate variable approach. DEGs post-transplant were
      identified by controlling false discovery rate (FDR) at < 0.01 with at least a 2
      fold change in expression from pre-transplant. The top 5 DEGs with higher levels
      of transcripts in blood at week 1 were TOMM40L, TMEM205, OLFM4, MMP8, and OSBPL9
      compared to baseline. The top 5 DEGs with lower levels at week 1 post-transplant
      were IL7R, KLRC3, CD3E, CD3D, and KLRC2 (Striking Image) compared to baseline.
      The top pathways from genes with lower levels at 1 week post-transplant compared
      to baseline, were T cell receptor signaling and iCOS-iCOSL signaling while the
      top pathways from genes with higher levels than baseline were axonal guidance
      signaling and LXR/RXR activation. Gene expression signatures at month 3 were
      similar to week 1. DEGs at 6 months post-transplant create a different gene
      signature than week 1 or month 3 post-transplant. RNAseq analysis identified more
      DEGs with lower than higher levels in blood compared to baseline at week 1 and
      month 3. The number of DEGs decreased with time post-transplant. Further
      investigations to determine the specific lymphocyte(s) responsible for
      differential gene expression may be important in selecting and personalizing
      immune suppressant drugs and may lead to targeted therapies. 

PMID- 25946141
TI  - The children's cliff--extending CHIP.

PMID- 25946142
TI  - The Affordable Care Act at 5 Years.

PMID- 25946143
TI  - Progress and Hurdles for Follow-on Biologics.

PMID- 25946146
TI  - Correction: Identification of Reference Genes for Quantitative Expression
      Analysis of MicroRNAs and mRNAs in Barley under Various Stress Conditions.

PMID- 25946144
TI  - Diabetic foot complications and their risk factors from a large retrospective
      cohort study.
AB  - BACKGROUND: Foot complications are considered to be a serious consequence of
      diabetes mellitus, posing a major medical and economical threat. Identifying the
      extent of this problem and its risk factors will enable health providers to set
      up better prevention programs. Saudi National Diabetes Registry (SNDR), being a
      large database source, would be the best tool to evaluate this problem. METHODS:
      This is a cross-sectional study of a cohort of 62,681 patients aged >= 25 years
      from SNDR database, selected for studying foot complications associated with
      diabetes and related risk factors. RESULTS: The overall prevalence of diabetic
      foot complications was 3.3% with 95% confidence interval (95% CI) of (3.16%
      3.44%), whilst the prevalences of foot ulcer, gangrene, and amputations were
      2.05% (1.94%-2.16%), 0.19% (0.16%-0.22%), and 1.06% (0.98%-1.14%), respectively.
      The prevalence of foot complications increased with age and diabetes duration
      predominantly amongst the male patients. Diabetic foot is more commonly seen
      among type 2 patients, although it is more prevalent among type 1 diabetic
      patients. The Univariate analysis showed Charcot joints, peripheral vascular
      disease (PVD), neuropathy, diabetes duration >= 10 years, insulin use,
      retinopathy, nephropathy, age >= 45 years, cerebral vascular disease (CVD), poor
      glycemic control, coronary artery disease (CAD), male gender, smoking, and
      hypertension to be significant risk factors with odds ratio and 95% CI at 42.53
      (18.16-99.62), 14.47 (8.99-23.31), 12.06 (10.54-13.80), 7.22 (6.10-8.55), 4.69
      (4.28-5.14), 4.45 (4.05-4.89), 2.88 (2.43-3.40), 2.81 (2.31-3.43), 2.24 (1.98
      2.45), 2.02 (1.84-2.22), 1.54 (1.29-1.83), and 1.51 (1.38-1.65), respectively.
      CONCLUSIONS: Risk factors for diabetic foot complications are highly prevalent;
      they have put these complications at a higher rate and warrant primary and
      secondary prevention programs to minimize morbidity and mortality in addition to
      economic impact of the complications. Other measurements, such as decompression
      of lower extremity nerves, should be considered among diabetic patients.

PMID- 25946145
TI  - Utilization of a balanced steady state free precession signal model for improved
      fat/water decomposition.
AB  - PURPOSE: Chemical shift based fat/water decomposition methods such as IDEAL are
      frequently used in challenging imaging environments with large B0 inhomogeneity.
      However, they do not account for the signal modulations introduced by a balanced
      steady state free precession (bSSFP) acquisition. Here we demonstrate improved
      performance when the bSSFP frequency response is properly incorporated into the
      multipeak spectral fat model used in the decomposition process. THEORY AND
      METHODS: Balanced SSFP allows for rapid imaging but also introduces a
      characteristic frequency response featuring periodic nulls and pass bands. Fat
      spectral components in adjacent pass bands will experience bulk phase offsets and
      magnitude modulations that change the expected constructive and destructive
      interference between the fat spectral components. A bSSFP signal model was
      incorporated into the fat/water decomposition process and used to generate images
      of a fat phantom, and bilateral breast and knee images in four normal volunteers
      at 1.5 Tesla. RESULTS: Incorporation of the bSSFP signal model into the
      decomposition process improved the performance of the fat/water decomposition.
      CONCLUSION: Incorporation of this model allows rapid bSSFP imaging sequences to
      use robust fat/water decomposition methods such as IDEAL. While only one set of
      imaging parameters were presented, the method is compatible with any field
      strength or repetition time.

PMID- 25946148
TI  - Reactions to ingroup and outgroup deviants: an experimental group paradigm for
      black sheep effect.
AB  - In the classic black sheep effect (BSE) an ingroup deviant member is usually
      evaluated more negatively than the corresponding outgroup deviant. This effect is
      usually obtained by using scenarios and asking people to imagine the situation as
      vividly as possible. The present study proposes a new method to investigate the
      BSE by considering the behavioral and physiological reactions to unfair behavior
      (aggressive game behavior) in a realistic experimental group-setting. The study
      involved 52 university students in a minimal group setting who performed a
      modified version of the competitive reaction time (CRT) task adapted to be played
      in groups of four people. The classic BSE was replicated for evaluation but not
      for the behavioral reactions (retaliate to aggression) to deviants. More
      interestingly, a negative relationship emerged in the ingroup deviant condition
      between the level of behavioral derogation and the systolic blood pressure level.

PMID- 25946147
TI  - Resveratrol ameliorates abnormalities of fluid and electrolyte secretion in a
      hypoxia-Induced model of acquired CFTR deficiency.
AB  - OBJECTIVE/HYPOTHESIS: Ineffective mucociliary clearance (MCC) is a common
      pathophysiologic process that underlies airway inflammation and infection. A
      dominant fluid and electrolyte secretory pathway in the nasal airways is governed
      by the cystic fibrosis transmembrane conductance regulator (CFTR). Decreased
      transepithelial Cl(-) transport secondary to an acquired CFTR deficiency may
      exacerbate respiratory epithelial dysfunction by diminishing MCC and increasing
      mucus viscosity. The objectives of the present study are to 1) develop a model of
      acquired CFTR deficiency in sinonasal epithelium using hypoxia, 2) investigate
      whether the polyphenol resveratrol promotes CFTR-mediated anion transport, 3)
      explore resveratrol mechanism of action and determine therapeutic suitability for
      overcoming acquired CFTR defects, and 4) test the drug in the hypoxic model of
      acquired CFTR deficiency in preparation for a clinical trial in human sinus
      disease. We hypothesize that hypoxia will induce depletion of airway surface
      liquid (ASL) secondary to acquired CFTR deficiency and that resveratrol will
      restore transepithelial Cl(-) secretion and recover ASL hydration. STUDY DESIGN:
      Basic science. METHODS: Murine nasal septal (MNSE) and human sinonasal epithelial
      (HSNE) cultures were incubated under hypoxic conditions (1% O2 , 5% CO2 ) and
      transepithelial ion transport (change in short-circuit current = DeltaISC )
      evaluated in Ussing chambers. Resveratrol was tested using primary cells and
      HEK293 cells expressing human CFTR by Ussing chamber and patch clamp techniques
      under both phosphorylating and nonphosphorylating conditions. CFTR activation was
      evaluated in human explants and by murine in vivo (nasal potential difference)
      assessment. Cellular cyclic adenosine monophosphate (cAMP) (ELISA) and subsequent
      CFTR regulatory domain (R-D) phosphorylation (gel-shift assay) were also
      evaluated. Effects of hypoxia and resveratrol on ASL were tested using confocal
      laser scanning microscopy (CLSM) and micro-optical coherence tomography (uOCT).
      RESULTS: Hypoxia significantly decreased DeltaISC (in uA/cm(2) ) attributable to
      CFTR at 12 and 24 hours of exposure in both MNSE (13.55 +/- 0.46 [12 hours];
      12.75 +/- 0.07 [24 hours] vs. 19.23 +/- 0.18 [control]; P < 0.05) and HSNE (19.55
      +/- 0.56 [12 hours]; 17.67 +/- 1.13 [24 hours] vs. 25.49 +/- 1.48 [control]; P <
      0.05). We have shown that resveratrol (100 MUM) enhanced CFTR-dependent Cl(-)
      secretion in HSNE to an extent comparable to the recently Food and Drug
      Administration-approved CFTR potentiator, ivacaftor. Cl(-) transport across human
      sinonasal explants (78.42 +/- 1.75 vs. 1.75 +/- 1.5 [control]; P < 0.05) and in
      vivo murine nasal epithelium (-4 +/- 1.8 vs. -0.8 +/- 1.7 mV [control]; P < 0.05)
      were also significantly increased by the drug. No increase in cAMP or CFTR R-D
      phosphorylation was detected. Inside-out patches showed increased CFTR open
      probability (NPo/N (N = channel number]) compared to controls in both MNSE (0.329
      +/- 0.116 vs. 0.119 +/- 0.059 [control]; P < 0.05) and HEK293 cells (0.22 +/-
      0.048 vs. 0.125 +/- 0.07 [control]; P < 0.05). ASL thickness was decreased under
      hypoxic conditions when measured by CLSM (4.19 +/- 0.44 vs. 6.88 +/- 0.67
      [control]; P < 0.05). A 30-minute apical application of resveratrol increased ASL
      depth in normal epithelium (8.08 +/- 1.68 vs. 6.11 +/- 0.47 [control]; P < 0.05).
      Furthermore, hypoxia-induced abnormalities of fluid and electrolyte secretion in
      sinonasal epithelium were restored with resveratrol treatment (5.55 +/- 0.74 vs.
      3.13 +/- 0.17 [control]; P < 0.05). CONCLUSIONS: CFTR activation with a leading
      edge Cl(-) secretagogue such as resveratrol represents an innovative approach to
      overcoming acquired CFTR defects in sinus and nasal airway disease. This exciting
      new strategy bears further testing in non-CF individuals with chronic
      rhinosinusitis. LEVEL OF EVIDENCE: N/A. Laryngoscope, 125:S1-S13, 2015.

PMID- 25946149
TI  - Accuracy of computed tomography to predict extracapsular spread in p16-positive
      squamous cell carcinoma.
AB  - OBJECTIVE: To determine the accuracy of pretreatment, contrast-enhanced computed
      tomography (CT) in the diagnosis of extracapsular spread (ECS) in cervical lymph
      node metastases from p16-positive head-and-neck squamous cell carcinoma (HNSCC).
      STUDY DESIGN: Retrospective observational study. METHODS: Sixty-five (n = 65)
      patients diagnosed between 2004 and 2013 with p16-positive HNSCC and with
      cervical lymph node metastases measuring at least 1 centimeter in diameter on
      pathological assessment were included. All patients underwent primary surgical
      treatment. Subjects' preoperative contrast-enhanced neck CT scans were
      independently assigned a score for the likelihood of ECS (5-point scale) by two
      board-certified neuroradiologists. Receiver-operating characteristic curves were
      generated, and optimal sensitivity, specificity, positive predictive value (PPV),
      negative predictive value (NPV), and accuracy were calculated for each
      radiologist. RESULTS: On histological analysis, the majority of patients (58%;
      38/65) were found to have ECS, and 29% (19/65) of patients had >= three
      metastatic lymph nodes. For radiologist 1, PPV and NPV for ECS detection were 72%
      (95% confidence interval (CI), 53%-87%) and 53% (95% CI, 36%-70%), respectively.
      For radiologist 2, PPV and NPV for ECS detection were 82% (95% CI, 60 %-95%) and
      53% (95% CI, 38%-69%), respectively. CONCLUSION: CT is not a reliable method for
      determining the presence of ECS in p16-positive HNSCC patients.

PMID- 25946150
TI  - The ERECTA, CLAVATA and class III HD-ZIP Pathways Display Synergistic
      Interactions in Regulating Floral Meristem Activities.
AB  - In angiosperms, the production of flowers marks the beginning of the reproductive
      phase. At the emergence of flower primordia on the flanks of the inflorescence
      meristem, the WUSCHEL (WUS) gene, which encodes a homeodomain transcription
      factor starts to be expressed and establishes de novo stem cell population,
      founder of the floral meristem (FM). Similarly to the shoot apical meristem a
      precise spatial and temporal expression pattern of WUS is required and maintained
      through strict regulation by multiple regulatory inputs to maintain stem cell
      homeostasis. However, following the formation of a genetically determined fixed
      number of floral organs, this homeostasis is shifted towards organogenesis and
      the FM is terminated. In here we performed a genetic study to test how a
      reduction in ERECTA, CLAVATA and class III HD-ZIP pathways affects floral
      meristem activity and flower development. We revealed strong synergistic
      phenotypes of extra flower number, supernumerary whorls, total loss of
      determinacy and extreme enlargement of the meristem as compared to any double
      mutant combination indicating that the three pathways, CLV3, ER and HD-ZIPIII
      distinctively regulate meristem activity and that they act in parallel. Our
      findings yield several new insights into stem cell-driven development. We
      demonstrate the crucial requirement for coupling floral meristem termination with
      carpel formation to ensure successful reproduction in plants. We also show how
      regulation of meristem size and alternation in spatial structure of the meristem
      serve as a mechanism to determine flower organogenesis. We propose that the loss
      of FM determinacy due to the reduction in CLV3, ER and HD-ZIPIII activity is
      genetically separable from the AGAMOUS core mechanism of meristem termination. 

PMID- 25946151
TI  - Biomarkers of therapeutic responses in chronic Chagas disease: state of the art
      and future perspectives.
AB  - The definition of a biomarker provided by the World Health Organization is any
      substance, structure, or process that can be measured in the body, or its
      products and influence, or predict the incidence or outcome of disease.
      Currently, the lack of prognosis and progression markers for chronic Chagas
      disease has posed limitations for testing new drugs to treat this neglected
      disease. Several molecules and techniques to detect biomarkers in Trypanosoma
      cruzi-infected patients have been proposed to assess whether specific treatment
      with benznidazole or nifurtimox is effective. Isolated proteins or protein groups
      from different T. cruzi stages and parasite-derived glycoproteins and synthetic
      neoglycoconjugates have been demonstrated to be useful for this purpose, as have
      nucleic acid amplification techniques. The amplification of T. cruzi DNA using
      the real-time polymerase chain reaction method is the leading test for assessing
      responses to treatment in a short period of time. Biochemical biomarkers have
      been tested early after specific treatment. Cytokines and surface markers
      represent promising molecules for the characterisation of host cellular
      responses, but need to be further assessed. 

PMID- 25946152
TI  - A novel ABCG-like transporter of Trypanosoma cruzi is involved in natural
      resistance to benznidazole.
AB  - Benznidazole (BZ) is one of the two drugs used for Chagas disease treatment.
      Nevertheless therapeutic failures of BZ have been reported, which were mostly
      attributed to variable drug susceptibility among Trypanosoma cruzi strains. ATP
      binding cassette (ABC) transporters are involved in a variety of translocation
      processes and some members have been implicated in drug resistance. Here we
      report the characterisation of the first T. cruzi ABCG transporter gene, named
      TcABCG1, which is over-expressed in parasite strains naturally resistant to BZ.
      Comparison of TcABCG1 gene sequence of two TcI BZ-resistant strains with CL
      Brener BZ-susceptible strain showed several single nucleotide polymorphisms,
      which determined 11 amino acid changes. CL Brener transfected with TcI
      transporter genes showed 40-47% increased resistance to BZ, whereas no
      statistical significant increment in drug resistance was observed when CL Brener
      was transfected with the homologous gene. Only in the parasites transfected with
      TcI genes there was 2-2.6-fold increased abundance of TcABCG1 transporter
      protein. The analysis in wild type strains also suggests that the level of
      TcABCG1 transporter is related to BZ natural resistance. The characteristics of
      untranslated regions of TcABCG1 genes of BZ-susceptible and resistant strains
      were investigated by computational tools. 

PMID- 25946153
TI  - Immunological response to re-infections with clones of the Colombian strain of
      Trypanosoma cruzi with different degrees of virulence: influence on pathological
      features during chronic infection in mice.
AB  - Re-infections with Trypanosoma cruzi are an aggravating factor for Chagas disease
      morbidity. The Colombian strain of T. cruzi represents multiclonal populations
      formed by clonally propagating organisms with different tropisms and degrees of
      virulence. In the present study, the influence of successive inoculations with
      clones of the Colombian strain, exhibiting different degrees of virulence, on
      chronic myocarditis and the humoral and cellular immune responses (Col-C1 high
      virulence, Col-C8 medium virulence and Col-C5 low virulence) were demonstrated.
      Mice from three groups with a single infection were evaluated during the acute
      (14th-30th day) and chronic phases for 175 days. An immunofluorescence assay,
      ELISA and delayed type hypersensitivity (DTH) cutaneous test were also performed.
      Mice with a triple infection were studied on the 115th-175th days following first
      inoculation. The levels of IgM and IgG2a were higher in the animals with a triple
      infection. DTH showed a higher intensity in the inflammatory infiltrate based on
      the morphometric analysis during a 48 h period of the triple infection and at 24
      h with a single infection. The histopathology of the heart demonstrated
      significant exacerbation of cardiac inflammatory lesions confirmed by the
      morphometric test. The humoral responses indicate a reaction to the triple
      infection, even with clones of the same strain. 

PMID- 25946154
TI  - Mass trapping with MosquiTRAPs does not reduce Aedes aegypti abundance.
AB  - The objective of this study was to evaluate the effectiveness of Aedes aegypti
      mass trapping using the sticky trap MosquiTRAP (MQT) by performing a cluster
      randomised controlled trial in Manaus, state of Amazonas, Brazil. After an
      initial questionnaire and baseline monitoring of adult Ae. aegypti abundance with
      BG-Sentinel (BGS) traps in six clusters, three clusters were randomly assigned to
      the intervention arm where each participating household received three MQTs for
      mass trapping during 17 months. The remaining three clusters (control arm) did
      not receive traps. The effect of mass trapping on adult Ae. aegypti abundance was
      monitored fortnightly with BGS traps. During the last two months of the study, a
      serological survey was conducted. After the study, a second questionnaire was
      applied in the intervention arm. Entomological monitoring indicated that MQT mass
      trapping did not reduce adult Ae. aegypti abundance. The serological survey
      indicated that recent dengue infections were equally frequent in the intervention
      and the control arm. Most participants responded positively to questions
      concerning user satisfaction. According to the results, there is no evidence that
      mass trapping with MQTs can be used as a part of dengue control programs. The use
      of this sticky trap is only recommendable for dengue vector monitoring. 

PMID- 25946155
TI  - Update on oral Chagas disease outbreaks in Venezuela: epidemiological, clinical
      and diagnostic approaches.
AB  - Orally transmitted Chagas disease has become a matter of concern due to outbreaks
      reported in four Latin American countries. Although several mechanisms for orally
      transmitted Chagas disease transmission have been proposed, food and beverages
      contaminated with whole infected triatomines or their faeces, which contain
      metacyclic trypomastigotes of Trypanosoma cruzi, seems to be the primary vehicle.
      In 2007, the first recognised outbreak of orally transmitted Chagas disease
      occurred in Venezuela and largest recorded outbreak at that time. Since then, 10
      outbreaks (four in Caracas) with 249 cases (73.5% children) and 4% mortality have
      occurred. The absence of contact with the vector and of traditional cutaneous and
      Romana's signs, together with a florid spectrum of clinical manifestations during
      the acute phase, confuse the diagnosis of orally transmitted Chagas disease with
      other infectious diseases. The simultaneous detection of IgG and IgM by ELISA and
      the search for parasites in all individuals at risk have been valuable diagnostic
      tools for detecting acute cases. Follow-up studies regarding the microepidemics
      primarily affecting children has resulted in 70% infection persistence six years
      after anti-parasitic treatment. Panstrongylus geniculatus has been the
      incriminating vector in most cases. As a food-borne disease, this entity requires
      epidemiological, clinical, diagnostic and therapeutic approaches that differ from
      those approaches used for traditional direct or cutaneous vector transmission.

PMID- 25946156
TI  - Infection with Trypanosoma cruzi TcII and TcI in free-ranging population of lion
      tamarins (Leontopithecus spp): an 11-year follow-up.
AB  - Here, we present a review of the dataset resulting from the 11-years follow-up of
      Trypanosoma cruzi infection in free-ranging populations of Leontopithecus rosalia
      (golden lion tamarin) and Leontopithecus chrysomelas (golden-headed lion tamarin)
      from distinct forest fragments in Atlantic Coastal Rainforest. Additionally, we
      present new data regarding T. cruzi infection of small mammals (rodents and
      marsupials) that live in the same areas as golden lion tamarins and
      characterisation at discrete typing unit (DTU) level of 77 of these isolates. DTU
      TcII was found to exclusively infect primates, while TcI infected Didelphis
      aurita and lion tamarins. The majority of T. cruzi isolates derived from L.
      rosalia were shown to be TcII (33 out 42) Nine T. cruzi isolates displayed a TcI
      profile. Golden-headed lion tamarins demonstrated to be excellent reservoirs of
      TcII, as 24 of 26 T. cruzi isolates exhibited the TcII profile. We concluded the
      following: (i) the transmission cycle of T. cruzi in a same host species and
      forest fragment is modified over time, (ii) the infectivity competence of the
      golden lion tamarin population fluctuates in waves that peak every other year and
      (iii) both golden and golden-headed lion tamarins are able to maintain long
      lasting infections by TcII and TcI.

PMID- 25946157
TI  - Retrospective distribution of Trypanosoma cruzi I genotypes in Colombia.
AB  - Trypanosoma cruzi is the aetiological agent of Chagas disease, which affects
      approximately eight million people in the Americas. This parasite exhibits
      genetic variability, with at least six discrete typing units broadly distributed
      in the American continent. T. cruzi I (TcI) shows remarkable genetic diversity; a
      genotype linked to human infections and a domestic cycle of transmission have
      recently been identified, hence, this strain was named TcIDom. The aim of this
      work was to describe the spatiotemporal distribution of TcI subpopulations across
      humans, insect vectors and mammalian reservoirs in Colombia by means of molecular
      typing targeting the spliced leader intergenic region of mini-exon gene. We
      analysed 101 TcI isolates and observed a distribution of sylvatic TcI in 70% and
      TcIDom in 30%. In humans, the ratio was sylvatic TcI in 60% and TcIDom in 40%. In
      mammal reservoirs, the distribution corresponded to sylvatic TcI in 96% and
      TcIDom in 4%. Among insect vectors, sylvatic TcI was observed in 48% and TcIDom
      in 52%. In conclusion, the circulation of TcIDom is emerging in Colombia and this
      genotype is still adapting to the domestic cycle of transmission. The
      epidemiological and clinical implications of these findings are discussed herein.

PMID- 25946158
TI  - Where do these bugs come from? Phenotypic structure of Triatoma infestans
      populations after control interventions in the Argentine Chaco.
AB  - House re-invasion by native triatomines after insecticide-based control campaigns
      represents a major threat for Chagas disease vector control. We conducted a
      longitudinal intervention study in a rural section (Area III, 407 houses) of
      Pampa del Indio, northeastern Argentina, and used wing geometric morphometry to
      compare pre-spray and post-spray (re-infestant bugs) Triatoma infestans
      populations. The community-wide spraying with pyrethroids reduced the prevalence
      of house infestation by T. infestans from 31.9% to < 1% during a four-year follow
      up, unlike our previous studies in the neighbouring Area I. Two groups of bug
      collection sites differing in wing shape variables before interventions
      (including 221 adults from 11 domiciles) were used as a reference for assigning
      44 post-spray adults. Wing shape variables from post-spray, high-density bug
      colonies and pre-spray groups were significantly different, suggesting that re
      infestant insects had an external origin. Insects from one house differed
      strongly in wing shape variables from all other specimens. A further comparison
      between insects from both areas supported the existence of independent re
      infestation processes within the same district. These results point to local
      heterogeneities in house re-infestation dynamics and emphasise the need to expand
      the geographic coverage of vector surveillance and control operations to the
      affected region.

PMID- 25946159
TI  - Reaching for the Holy Grail: insights from infection/cure models on the prospects
      for vaccines for Trypanosoma cruzi infection.
AB  - Prevention of Trypanosoma cruzi infection in mammals likely depends on either
      prevention of the invading trypomastigotes from infecting host cells or the rapid
      recognition and killing of the newly infected cells by T. cruzi-specific T cells.
      We show here that multiple rounds of infection and cure (by drug therapy) fails
      to protect mice from reinfection, despite the generation of potent T cell
      responses. This disappointing result is similar to that obtained with many other
      vaccine protocols used in attempts to protect animals from T. cruzi infection. We
      have previously shown that immune recognition of T. cruzi infection is
      significantly delayed both at the systemic level and at the level of the infected
      host cell. The systemic delay appears to be the result of a stealth infection
      process that fails to trigger substantial innate recognition mechanisms while the
      delay at the cellular level is related to the immunodominance of highly variable
      gene family proteins, in particular those of the trans-sialidase family. Here we
      discuss how these previous studies and the new findings herein impact our
      thoughts on the potential of prophylactic vaccination to serve a productive role
      in the prevention of T. cruzi infection and Chagas disease.

PMID- 25946160
TI  - Associations between Familial Factor, Trait Conscientiousness, Gender and the
      Occurrence of Type 2 Diabetes in Adulthood: Evidence from a British Cohort.
AB  - OBJECTIVE: To investigate social, familial, and psychological factors in
      influencing the occurrence of type 2 diabetes in adulthood. METHOD: Some 17,415
      babies born in Great Britain in 1958 and followed up at 7, 11, 33, and 50 years
      of age. The prevalence of type 2 diabetes at age 50 years was the outcome
      measure. RESULTS: Some 5,032 participants with data on parental social class,
      childhood cognitive ability tests scores at age 11 years, educational
      qualifications at age 33 years, personality traits, occupational levels, and type
      2 diabetes (all measured at age 50 years) were included in the study. Available
      information also included whether cohort members' parents or siblings had
      diabetes. Using logistic regression analyses, results showed that sex (OR=0.63:
      0.42-0.92, p<.05), family history (OR=3.40: 1.76-6.55, p<.01), and trait
      conscientiousness (OR=0.76: 0.64-0.90, p<.001) were all significantly and
      independently associated with the occurrence of type 2 diabetes in adulthood. It
      appears that the occurrence of type 2 diabetes is greater among men than women
      (4.3% vs 2.5%). CONCLUSION: Familial (genetic and non-genetic) and psychological
      factors are significantly associated with the prevalence of type 2 diabetes in
      adulthood.

PMID- 25946161
TI  - Molecular structure-affinity relationship of bufadienolides and human serum
      albumin in vitro and molecular docking analysis.
AB  - The development of bufadienolides as anti-tumor agents is limited due to poor
      pharmacokinetic properties regarding drug half-lives and toxicity in vivo. These
      serious factors might be improved by increasing the drug/albumin-binding ratio.
      This study therefore investigated the relationship between the structural
      properties of nine bufadienolides and their affinities for human serum albumin
      (HSA) by a fluorescence spectroscopy-based analysis and molecular docking.
      Fluorescence quenching data showed that the interaction of each bufadienolide
      with HSA formed a non-fluorescent complex, while thermodynamic parameters
      revealed negative DeltaS and DeltaH values, corresponding to changes in enthalpy
      and entropy, respectively. The structural differences between the various
      bufadienolides markedly influenced their binding affinity for HSA. With the
      exception of a C = O bond at the C12 position that decreased the binding affinity
      for HSA, other polar groups tended to increase the affinity, especially a
      hydroxyl (OH) group at assorted bufadienolide sites. The rank order of binding
      affinities for drugs with tri-hydroxyl groups was as follows: 11-OH > 5-OH > 16
      OH; in addition, 16-acetoxy (OAc), 10-aldehyde and 14-epoxy constituents notably
      enhanced the binding affinity. Among these groups, 11-OH and 16-acetyl were
      especially important for a seamless interaction between the bufadienolides and
      HSA. Furthermore, molecular docking analysis revealed that either an 11-OH or a
      16-OAc group spatially close to a five-membered lactone ring significantly
      facilitated the anchoring of these compounds within site I of the HSA pocket via
      hydrogen bonding (H-bonding) with Tyr150 or Lys199, respectively. In summary,
      bufadienolide structure strongly affects binding with HSA, and 11-OH or 16-OAc
      groups improve the drug association with key amino acid residues. This
      information is valuable for the prospective development of bufadienolides with
      improved pharmacological profiles as novel anti-tumor drugs. 

PMID- 25946162
TI  - Age at First Delivery and Osteoporosis Risk in Korean Postmenopausal Women: The
      2008-2011 Korea National Health and Nutrition Examination Survey (KNHANES).
AB  - It has been reported in several studies that there may be a significant
      correlation between reproductive history and the risk of osteoporosis due to the
      effect of estrogen. Under this hypothesis, however, it is unclear whether the age
      at first delivery has any major influences on the risk of osteoporosis.
      Therefore, this study aimed to investigate the relationship between the age at
      first delivery and the risk of osteoporosis in Korean menopausal women. This
      study was performed using data from the 2008-2011 Korea National Health and
      Nutrition Examination Survey and included 2,530 Korean postmenopausal women. The
      diagnosis of osteoporosis was made using the World Health Organization T-score
      criteria (T-score <= -2.5, at the femoral neck or lumbar spine). Participants
      were categorized into 3 groups according to age at first delivery: <= 23, 24-29,
      and >= 30 years. Older age, lower body mass index, lower calcium intake, later
      menarche, and earlier menopause increased the risk of osteoporosis, whereas
      hormone therapy and oral contraceptive use were associated with a decreased risk
      of osteoporosis. Postmenopausal women whose first delivery occurred at age 24-29
      years were shown to have a significantly increased risk of osteoporosis (odds
      ratio, 2.124; 95% confidence interval, 1.096-4.113; P = 0.026) compared to those
      who first gave birth after the age of 30 years. These findings suggest that
      postmenopausal women whose first delivery occurred in their mid to late 20s, a
      period during which bone mass slowly accumulates to the peak, are at an increased
      risk of osteoporosis.

PMID- 25946163
TI  - The Effects of a Sport-Specific Maximal Strength and Conditioning Training on
      Critical Velocity, Anaerobic Running Distance, and 5-km Race Performance.
AB  - PURPOSE: To investigate the effects of a sport-specific maximal 6-wk strength and
      conditioning program on critical velocity (CV), anaerobic running distance (ARD),
      and 5-km time-trial performance (TT). METHODS: 16 moderately trained recreational
      endurance runners were tested for CV, ARD, and TT performances on 3 separate
      occasions (baseline, midstudy, and poststudy). DESIGN: Participants were randomly
      allocated into a strength and conditioning group (S&C; n = 8) and a comparison
      endurance-training-only group (EO; n = 8). During the first phase of the study (6
      wk), the S&C group performed concurrent maximal strength and endurance training,
      while the EO group performed endurance-only training. After the retest of all
      variables (midstudy), both groups subsequently, during phase 2, performed another
      6 wk of endurance-only training that was followed by poststudy tests. RESULTS: No
      significant change for CV was identified in either group. The S&C group
      demonstrated a significant decrease for ARD values after phases 1 and 2 of the
      study. TT performances were significantly different in the S&C group after the
      intervention, with a performance improvement of 3.62%. This performance increase
      returned close to baseline after the 6-wk endurance-only training. CONCLUSION:
      Combining a 6-wk resistance-training program with endurance training
      significantly improves 5-km TT performance. Removing strength training results in
      some loss of those performance improvements.

PMID- 25946165
TI  - Self-Assembled Hybrids of Fluorescent Carbon Dots and PAMAM Dendrimers for
      Epirubicin Delivery and Intracellular Imaging.
AB  - Advanced nanomaterials integrating imaging and therapeutic modalities on a single
      platform offers a new horizon in current cancer treatment strategies. Recently,
      carbon dots (CQDs) have been successfully employed for bioimaging of cancer
      cells. In the present study, luminescent CQDs with anionic terminus and cationic
      acetylated G5 poly(amido amine) (G5-Ac85) dendrimers were combined via
      noncovalent interactions to form self-assembled fluorescent hybrids. The
      fluorescence of CQDs in hybrids is enhanced in the vicinity of primary amine
      groups of dendrimers, making them suitable as cellular imaging probes.
      Encapsulation of chemo-drug epirubicin (EPI) in the dendrimer interiors endowed
      the fluorescent hybrids with therapeutic potential. The in vitro release of an
      entrapped EPI drug from CQDs@EPI?G5-Ac85 hybrids was faster in an acidic
      environment than under physiological conditions. Herein, multifunctional
      CQDs@EPI?G5-Ac85 hybrids serve as a dual-emission delivery system, to track the
      intracellular distribution and cytotoxic effects of EPI drugs. Green emission
      properties of CQDs were used for fluorescence microscopic imaging and cellular
      uptake by flow cytometry. Cell cycle analysis, field-emission scanning electron
      microscopy (FE-SEM), reactive oxygen species (ROS) generation, and up-regulation
      of apoptotic signaling genes unanimously demonstrated the apoptosis inducing
      ability of CQDs@EPI?G5-Ac85 hybrids in breast cancer (MCF-7) cells. Therefore, we
      have evaluated CQDs@EPI?G5-Ac85 hybrids as prospective candidates to achieve
      simultaneous imaging and drug delivery in cancer cells. 

PMID- 25946164
TI  - Constructing rigorous and broad biosurveillance networks for detecting emerging
      zoonotic outbreaks.
AB  - Determining optimal surveillance networks for an emerging pathogen is difficult
      since it is not known beforehand what the characteristics of a pathogen will be
      or where it will emerge. The resources for surveillance of infectious diseases in
      animals and wildlife are often limited and mathematical modeling can play a
      supporting role in examining a wide range of scenarios of pathogen spread. We
      demonstrate how a hierarchy of mathematical and statistical tools can be used in
      surveillance planning help guide successful surveillance and mitigation policies
      for a wide range of zoonotic pathogens. The model forecasts can help clarify the
      complexities of potential scenarios, and optimize biosurveillance programs for
      rapidly detecting infectious diseases. Using the highly pathogenic zoonotic H5N1
      avian influenza 2006-2007 epidemic in Nigeria as an example, we determined the
      risk for infection for localized areas in an outbreak and designed
      biosurveillance stations that are effective for different pathogen strains and a
      range of possible outbreak locations. We created a general multi-scale, multi
      host stochastic SEIR epidemiological network model, with both short and long
      range movement, to simulate the spread of an infectious disease through Nigerian
      human, poultry, backyard duck, and wild bird populations. We chose parameter
      ranges specific to avian influenza (but not to a particular strain) and used a
      Latin hypercube sample experimental design to investigate epidemic predictions in
      a thousand simulations. We ranked the risk of local regions by the number of
      times they became infected in the ensemble of simulations. These spatial
      statistics were then complied into a potential risk map of infection. Finally, we
      validated the results with a known outbreak, using spatial analysis of all the
      simulation runs to show the progression matched closely with the observed
      location of the farms infected in the 2006-2007 epidemic. 

PMID- 25946166
TI  - DhITACT: DNA Hydrogel Formation by Isothermal Amplification of Complementary
      Target in Fluidic Channels.
AB  - DNA hydrogel formation by isothermal amplification of complementary targets in
      microfluidic channels (DhITACT) is a new platform for rapid and accurate
      detection of infectious pathogens. DNA hydrogel is formed in situ within
      microfluidic channels by the isothermal rolling circle amplification process upon
      the selective binding of target strands from the biological fluid. Once the
      volume of DNA hydrogel sufficiently enlarges, it can selectively block the
      matching channels with target pathogens. 

PMID- 25946167
TI  - Return to Preinjury Levels of Participation After Superior Labral Repair in
      Overhead Athletes: A Systematic Review.
AB  - CONTEXT: Athletes often preoperatively weigh the risks and benefits of electing
      to undergo an orthopaedic procedure to repair damaged tissue. A common concern
      for athletes is being able to return to their maximum levels of competition after
      shoulder surgery, whereas clinicians struggle with the ability to provide a
      consistent prognosis of successful return to participation after surgery. The
      variation in study details and rates of return in the existing literature have
      not supplied clinicians with enough evidence to give overhead athletes adequate
      information regarding successful return to participation when deciding to undergo
      shoulder surgery. OBJECTIVE: To investigate the odds of overhead athletes
      returning to preinjury levels of participation after arthroscopic superior labral
      repair. DATA SOURCES: The CINAHL, MEDLINE, and SPORTDiscus databases from 1972 to
      2013. STUDY SELECTION: The criteria for article selection were (1) The study was
      written in English. (2) The study reported surgical repair of an isolated
      superior labral injury or a superior labral injury with soft tissue debridement.
      (3) The study involved overhead athletes equal to or less than 40 years of age.
      (4) The study assessed return to the preinjury level of participation. DATA
      EXTRACTION: We critically reviewed articles for quality and bias and calculated
      and compared odds ratios for return to full participation for dichotomous
      populations or surgical procedures. DATA SYNTHESIS: Of 215 identified articles,
      11 were retained: 5 articles about isolated superior labral repair and 6 articles
      about labral repair with soft tissue debridement. The quality range was 11 to 17
      (42% to 70%) of a possible 24 points. Odds ratios could be generated for 8 of 11
      studies. Nonbaseball, nonoverhead, and nonthrowing athletes had a 2.3 to 5.8
      times greater chance of full return to participation than overhead/throwing
      athletes after isolated superior labral repair. Similarly, nonoverhead athletes
      had 1.5 to 3.5 times greater odds for full return than overhead athletes after
      labral repair with soft tissue debridement. In 1 study, researchers compared
      surgical procedures and found that overhead athletes who underwent isolated
      superior labral repair were 28 times more likely to return to full participation
      than those who underwent concurrent labral repair and soft tissue debridement (P
      < .05). CONCLUSIONS: The rate of return to participation after shoulder surgery
      within the literature is inconsistent. Odds of returning to preinjury levels of
      participation after arthroscopic superior labral repair with or without soft
      tissue debridement are consistently lower in overhead/throwing athletes than in
      nonoverhead/nonthrowing athletes. The variable rates of return within each group
      could be due to multiple confounding variables not consistently accounted for in
      the articles.

PMID- 25946169
TI  - Information recovery in behavioral networks.
AB  - In the context of agent based modeling and network theory, we focus on the
      problem of recovering behavior-related choice information from origin-destination
      type data, a topic also known under the name of network tomography. As a basis
      for predicting agents' choices we emphasize the connection between adaptive
      intelligent behavior, causal entropy maximization, and self-organized behavior in
      an open dynamic system. We cast this problem in the form of binary and weighted
      networks and suggest information theoretic entropy-driven methods to recover
      estimates of the unknown behavioral flow parameters. Our objective is to recover
      the unknown behavioral values across the ensemble analytically, without
      explicitly sampling the configuration space. In order to do so, we consider the
      Cressie-Read family of entropic functionals, enlarging the set of estimators
      commonly employed to make optimal use of the available information. More
      specifically, we explicitly work out two cases of particular interest: Shannon
      functional and the likelihood functional. We then employ them for the analysis of
      both univariate and bivariate data sets, comparing their accuracy in reproducing
      the observed trends. 

PMID- 25946168
TI  - Effect of performance improvement programs on compliance with sepsis bundles and
      mortality: a systematic review and meta-analysis of observational studies.
AB  - BACKGROUND: Several reports suggest that implementation of the Surviving Sepsis
      Campaign (SSC) guidelines is associated with mortality reduction in sepsis.
      However, adherence to the guideline-based resuscitation and management sepsis
      bundles is still poor. OBJECTIVE: To perform a systematic review of studies
      evaluating the impact of performance improvement programs on compliance with
      Surviving Sepsis Campaign (SSC) guideline-based bundles and/or mortality. DATA
      SOURCES: Medline (PubMed), Scopus and Intercollegiate Studies Institute Web of
      Knowledge databases from 2004 (first publication of the SSC guidelines) to
      October 2014. STUDY SELECTION: Studies on adult patients with sepsis, severe
      sepsis or septic shock that evaluated changes in compliance to
      individual/combined bundle targets and/or mortality following the implementation
      of performance improvement programs. Interventions may consist of educational
      programs, process changes or both. DATA EXTRACTION: Data from the included
      studies were extracted independently by two authors. Unadjusted binary data were
      collected in order to calculate odds ratios (OR) for compliance to
      individual/combined bundle targets. Adjusted (if available) or unadjusted data of
      mortality were collected. Random-effects models were used for the data synthesis.
      RESULTS: Fifty observational studies were selected. Despite high inconsistency
      across studies, performance improvement programs were associated with increased
      compliance with the complete 6-hour bundle (OR = 4.12 [95% confidence interval
      2.95-5.76], I(2) = 87.72%, k = 25, N = 50,081) and the complete 24-hour bundle
      (OR = 2.57 [1.74-3.77], I(2) = 85.22%, k = 11, N = 45,846) and with a reduction
      in mortality (OR = 0.66 [0.61-0.72], I(2) = 87.93%, k = 48, N = 434,447). Funnel
      plots showed asymmetry. CONCLUSIONS: Performance improvement programs are
      associated with increased adherence to resuscitation and management sepsis
      bundles and with reduced mortality in patients with sepsis, severe sepsis or
      septic shock.

PMID- 25946170
TI  - Spatial Heterogeneity of Soil Nutrients after the Establishment of Caragana
      intermedia Plantation on Sand Dunes in Alpine Sandy Land of the Tibet Plateau.
AB  - The Gonghe Basin region of the Tibet Plateau is severely affected by
      desertification. Compared with other desertified land, the main features of this
      region is windy, cold and short growing season, resulting in relatively difficult
      for vegetation restoration. In this harsh environment, identification the spatial
      distribution of soil nutrients and analysis its impact factors after vegetation
      establishment will be helpful for understanding the ecological relationship
      between soil and environment. Therefore, in this study, the 12-year-old C.
      intermedia plantation on sand dunes was selected as the experimental site. Soil
      samples were collected under and between shrubs on the windward slopes, dune tops
      and leeward slopes with different soil depth. Then analyzed soil organic matter
      (SOM), total nitrogen (TN), total phosphorus (TP), total potassium (TK),
      available nitrogen (AN), available phosphorus (AP) and available potassium (AK).
      The results showed that the spatial heterogeneity of soil nutrients was existed
      in C. intermedia plantation on sand dunes. (1) Depth was the most important
      impact factor, soil nutrients were decreased with greater soil depth. One of the
      possible reasons is that windblown fine materials and litters were accumulated on
      surface soil, when they were decomposed, more nutrients were aggregated on
      surface soil. (2) Topography also affected the distribution of soil nutrients,
      more soil nutrients distributed on windward slopes. The herbaceous coverage were
      higher and C. intermedia ground diameter were larger on windward slopes, both of
      them probably related to the high soil nutrients level for windward slopes. (3)
      Soil "fertile islands" were formed, and the "fertile islands" were more marked on
      lower soil nutrients level topography positions, while it decreased towards
      higher soil nutrients level topography positions. The enrichment ratio (E) for TN
      and AN were higher than other nutrients, most likely because C. intermedia is a
      leguminous shrub. 

PMID- 25946171
TI  - Purely endoscopic endonasal surgery of the craniovertebral junction: A systematic
      review.
AB  - BACKGROUND: Endoscopic endonasal surgery (EES) is a relatively novel approach to
      the craniovertebral junction (CVJ). The purpose of this analysis is to determine
      the surgical outcomes of patients who undergo purely EES of the CVJ. METHODS: A
      search for articles related to EES of the CVJ was performed using the
      MEDLINE/PubMed database. A bibliographic search was done for additional articles.
      Demographics, presenting symptoms, imaging findings, complications, follow-up,
      and patient outcomes were analyzed. RESULTS: Eighty-five patients from 30
      articles were included. The mean patient age was 47.9 +/- 24.8 years (range, 3 to
      96 years), with 44.7% being male. The most common presenting symptom was
      myelopathy (n = 64, 75.3%). The most common indications for surgery were
      brainstem compression secondary to basilar invagination (n = 41, 48.2%) and
      odontoid pannus (n = 20, 23.5%). Odontoidectomy was performed in 97.6% of cases.
      Intraoperative complications occurred in 16 patients (18.8%) and postoperative
      complications occurred in 18 patients (21.2%). Six patients developed
      postoperative respiratory failure necessitating a tracheostomy. Neurologic
      improvement was seen in 89.4% of patients at a mean follow-up of 22.2 months.
      CONCLUSION: Our analysis found that EES of the CVJ results in a high rate of
      neurologic improvement with acceptable complication rates. Given its minimally
      invasive nature and high success rate, this approach appears to be a reasonable
      alternative to the traditional transoral approach in select cases. This study
      represents the largest pooled sample size of EES of the CVJ to date. Increasing
      use of the endoscopic endonasal approach will allow for further studies with
      greater statistical power.

PMID- 25946172
TI  - Multiscale Informatics for Low-Temperature Propane Oxidation: Further
      Complexities in Studies of Complex Reactions.
AB  - The present paper describes further development of the multiscale informatics
      approach to kinetic model formulation of Burke et al. (Burke, M. P.;
      Klippenstein, S. J.; Harding, L. B. Proc. Combust. Inst. 2013, 34, 547-555) that
      directly incorporates elementary kinetic theories as a means to provide reliable,
      physics-based extrapolation of kinetic models to unexplored conditions. Here, we
      extend and generalize the multiscale informatics strategy to treat systems of
      considerable complexity-involving multiwell reactions, potentially missing
      reactions, nonstatistical product branching ratios, and non-Boltzmann (i.e.,
      nonthermal) reactant distributions. The methodology is demonstrated here for a
      subsystem of low-temperature propane oxidation, as a representative system for
      low-temperature fuel oxidation. A multiscale model is assembled and informed by a
      wide variety of targets that include ab initio calculations of molecular
      properties, rate constant measurements of isolated reactions, and complex systems
      measurements. Active model parameters are chosen to accommodate both "parametric"
      and "structural" uncertainties. Theoretical parameters (e.g., barrier heights)
      are included as active model parameters to account for parametric uncertainties
      in the theoretical treatment; experimental parameters (e.g., initial
      temperatures) are included to account for parametric uncertainties in the
      physical models of the experiments. RMG software is used to assess potential
      structural uncertainties due to missing reactions. Additionally, branching ratios
      among product channels are included as active model parameters to account for
      structural uncertainties related to difficulties in modeling sequences of
      multiple chemically activated steps. The approach is demonstrated here for
      interpreting time-resolved measurements of OH, HO2, n-propyl, i-propyl, propene,
      oxetane, and methyloxirane from photolysis-initiated low-temperature oxidation of
      propane at pressures from 4 to 60 Torr and temperatures from 300 to 700 K. In
      particular, the multiscale informed model provides a consistent quantitative
      explanation of both ab initio calculations and time-resolved species
      measurements. The present results show that interpretations of OH measurements
      are significantly more complicated than previously thought-in addition to barrier
      heights for key transition states considered previously, OH profiles also depend
      on additional theoretical parameters for R + O2 reactions, secondary reactions,
      QOOH + O2 reactions, and treatment of non-Boltzmann reaction sequences.
      Extraction of physically rigorous information from those measurements may require
      more sophisticated treatment of all of those model aspects, as well as additional
      experimental data under more conditions, to discriminate among possible
      interpretations and ensure model reliability. 

PMID- 25946174
TI  - Thriving through trust: ethical practice, quality care.

PMID- 25946173
TI  - Feedback valence affects auditory perceptual learning independently of feedback
      probability.
AB  - Previous studies have suggested that negative feedback is more effective in
      driving learning than positive feedback. We investigated the effect on learning
      of providing varying amounts of negative and positive feedback while listeners
      attempted to discriminate between three identical tones; an impossible task that
      nevertheless produces robust learning. Four feedback conditions were compared
      during training: 90% positive feedback or 10% negative feedback informed the
      participants that they were doing equally well, while 10% positive or 90%
      negative feedback informed them they were doing equally badly. In all conditions
      the feedback was random in relation to the listeners' responses (because the task
      was to discriminate three identical tones), yet both the valence (negative vs.
      positive) and the probability of feedback (10% vs. 90%) affected learning.
      Feedback that informed listeners they were doing badly resulted in better post
      training performance than feedback that informed them they were doing well,
      independent of valence. In addition, positive feedback during training resulted
      in better post-training performance than negative feedback, but only positive
      feedback indicating listeners were doing badly on the task resulted in learning.
      As we have previously speculated, feedback that better reflected the difficulty
      of the task was more effective in driving learning than feedback that suggested
      performance was better than it should have been given perceived task difficulty.
      But contrary to expectations, positive feedback was more effective than negative
      feedback in driving learning. Feedback thus had two separable effects on
      learning: feedback valence affected motivation on a subjectively difficult task,
      and learning occurred only when feedback probability reflected the subjective
      difficulty. To optimize learning, training programs need to take into
      consideration both feedback valence and probability. 

PMID- 25946175
TI  - Infection prevention: a patient safety imperative for the perioperative setting.

PMID- 25946176
TI  - A few minutes with Sharon Chappy.

PMID- 25946177
TI  - Infection prevention: the surgical care continuum.
AB  - Lack of careful attention to the increasing complexity of surgical procedures,
      instrument cleaning and processing, and the transition of surgical and other
      invasive procedures from the OR to areas outside the traditional hospital OR can
      contribute to surgical site infection (SSI) risk. Regardless of the location of
      an intervention, when basic infection prevention measures are applied reliably,
      even low infection rates can be reduced. To address infection prevention
      challenges, infection preventionists (IPs) must be well informed regarding
      infection risk and prevention during surgical and other invasive procedures and
      the effect a facility type may have on patients' infection risk. The IP must have
      a solid understanding of surgical asepsis, instrument disinfection, and
      sterilization to educate and support clinical teams in identifying opportunities
      for improvement relative to infection prevention. 

PMID- 25946178
TI  - A Review of the CDC Recommendations for Prevention of HAIs in Outpatient
      Settings.
AB  - According to the Centers for Disease Control and Prevention (CDC), most health
      care-associated infections (HAIs) are caused by contamination from the hands of
      health care providers or patients, contamination from the environment, and
      contamination from the patient's own skin. To mitigate common sources of
      infection transmission, frontline health care providers must be compliant with
      basic infection-prevention interventions, including hand hygiene, environmental
      cleaning and disinfection, safe injection practices, and designation of a trained
      health care professional to be responsible for the infection prevention and
      control program. Integration of CDC recommendations should incorporate a bundled
      approach to these interventions and should be part of a comprehensive approach to
      infection prevention and control. Effective infection-prevention practices in
      outpatient settings are critical for reducing the risk of infection transmission,
      improving patient safety and patient outcomes, and reducing costs associated with
      health care delivery.

PMID- 25946179
TI  - To bathe or not to bathe with chlorhexidine gluconate: is it time to take a stand
      for preadmission bathing and cleansing?

PMID- 25946180
TI  - Guideline implementation: surgical instrument cleaning.
AB  - Cleaning, decontaminating, and handling instructions for instruments vary widely
      based on the type of instrument and the manufacturer. Processing instruments in
      accordance with the manufacturer's instructions can help prevent damage and keep
      devices in good working order. Most importantly, proper cleaning and disinfection
      may prevent transmission of pathogenic organisms from a contaminated device to a
      patient or health care worker. The updated AORN "Guideline for cleaning and care
      of surgical instruments" provides guidance on cleaning, decontaminating,
      transporting, inspecting, and storing instruments. This article focuses on key
      points of the guideline to help perioperative personnel implement appropriate
      instrument care protocols in their practice settings. The key points address
      timely cleaning and decontamination of instruments after use; appropriate
      heating, ventilation, and air conditioning parameters for the decontamination
      area; processing of ophthalmic instruments and laryngoscopes; and precautions to
      take with instruments used in cases of suspected prion disease. Perioperative RNs
      should review the complete guideline for additional information and for guidance
      when writing and updating policies and procedures.

PMID- 25946181
TI  - Back to basics: specimen management.
AB  - Specific actions for handling various types of specimens may differ; however, the
      management process is essentially the same. Accurate specimen management requires
      effective multidisciplinary communication, minimal distractions, and awareness of
      the opportunities for error. When advocating for patients and working with
      members of the health care team to provide a safe perioperative environment,
      perioperative nurses should adhere to best practices for specimen management and
      strive to prevent specimen-related errors that may lead to inaccurate or
      incomplete diagnoses, the need for additional procedures, and perhaps most
      importantly, physical and psychological injury to patients. 

PMID- 25946182
TI  - Preventing venous thromboembolism in the ambulatory surgical setting.

PMID- 25946183
TI  - Human factors engineering: its place and potential in OR safety.

PMID- 25946185
TI  - Check the anesthesia machine.

PMID- 25946186
TI  - TIPE2 Inhibits Lung Cancer Growth Attributing to Promotion of Apoptosis by
      Regulating Some Apoptotic Molecules Expression.
AB  - Recent studies found that TIPE2 was involved in cancer development. However,
      little is known about TIPE2 in lung cancer. Our study aims to clarify the role of
      TIPE2 in lung carcinogenesis. We examined the expression of TIPE2 in lung
      squamous cancer (LSC), small cell lung cancer and lung adenocarcinoma (AdC)
      tissues and found that TIPE2 expression was lost in small cell lung cancer,
      compared with adjacent non-tumor tissues. Overexpression of TIPE2 significantly
      inhibited the growth of lung cancer cell H446 in vitro and even suppressed tumor
      formation in vivo. Flow cytometry analysis found TIPE2 overexpression promoted
      apoptosis of H446. In TIPE2 over-expression cells, caspase-3, caspase-9, and Bax
      were significantly up-regulated while Bcl-2 was down-regulated. Moreover,
      coincident results were shown by immunohistochemistry in tumors from nude mice.
      TIPE2 inhibited the phosphorylation of Akt, while promoting the phosphorylation
      of P38, but had no effect on IkappaBalpha and ERK pathway. Taken together, TIPE2
      promoted lung cancer cell apoptosis through affecting apoptosis-related molecules
      caspase-3, caspase-9, Bcl-2 and Bax, possibly via regulating P38 and Akt
      pathways, indicating that TIPE2 might be a novel marker for lung cancer diagnosis
      and therapy. 

PMID- 25946187
TI  - Managing Type 2 Diabetes Mellitus through Periodical Hospital Visits in the
      Aftermath of the Great East Japan Earthquake Disaster: A Retrospective Case
      Series.
AB  - AIMS: To assess the impact of the Great East Japan Earthquake Disaster on daily
      diabetes practice and to determine the feasibility of controlling type 2 diabetes
      mellitus in an outpatient department. METHODS: We retrospectively reviewed the
      data on disaster-affected patients with type 2 diabetes who periodically attended
      outpatient department of Soma Central Hospital. There were 767 patients with type
      2 diabetes mellitus in total. The primary outcome measure was the change in
      HbA1c. RESULTS: HbA1c levels of 58 patients with periodical hospital visits did
      not deteriorate after the disasters. Moreover, there observed no significant
      difference in the mean of HbA1c levels among all age and sex throughout the year.
      While several changes in diabetes medication usage occurred, DPP4-inhibitor was
      the only oral diabetic agent that increased in frequency (+60%). CONCLUSIONS:
      Patients with type 2 diabetes who were managed with periodical hospital visits
      did not show significant deterioration in HbA1c levels.

PMID- 25946188
TI  - Origin and Reticulate Evolutionary Process of Wheatgrass Elymus trachycaulus
      (Triticeae: Poaceae).
AB  - To study origin and evolutionary dynamics of tetraploid Elymus trachycaulus that
      has been cytologically defined as containing StH genomes, thirteen accessions of
      E. trachycaulus were analyzed using two low-copy nuclear gene Pepc
      (phosphoenolpyruvate carboxylase) and Rpb2 (the second largest subunit of RNA
      polymerase II), and one chloroplast region trnL-trnF (spacer between the tRNA Leu
      (UAA) gene and the tRNA-Phe (GAA) gene). Our chloroplast data indicated that
      Pseudoroegneria (St genome) was the maternal donor of E. trachycaulus. Rpb2 data
      indicated that the St genome in E. trachycaulus was originated from either P.
      strigosa, P. stipifolia, P. spicata or P. geniculate. The Hordeum (H genome)-like
      sequences of E. trachycaulus are polyphyletic in the Pepc tree, suggesting that
      the H genome in E. trachycaulus was contributed by multiple sources, whether due
      to multiple origins or introgression resulting from subsequent hybridization.
      Failure to recovering St copy of Pepc sequence in most accessions of E.
      trachycaulus might be caused by genome convergent evolution in allopolyploids.
      Multiple copies of H-like Pepc sequence from each accession with relative large
      deletions and insertions might be caused by either instability of Pepc sequence
      in H- genome or incomplete concerted evolution. Our results highlighted complex
      evolutionary history of E. trachycaulus. 

PMID- 25946190
TI  - Sex, Sport, IGF-1 and the Community Effect in Height Hypothesis.
AB  - We test the hypothesis that differences in social status between groups of people
      within a population may induce variation in insulin-like growth factor-1(IGF-1)
      levels and, by extension, growth in height. This is called the community effect
      in height hypothesis. The relationship between IGF-1, assessed via finger-prick
      dried blood spot, and elite level sport competition outcomes were analysed for a
      sample of 116 undergraduate men and women. There was a statistically significant
      difference between winners and losers of a competition. Winners, as a group, had
      higher average pre-game and post-game IGF-1 levels than losers. We proposed this
      type of difference as a proxy for social dominance. We found no evidence that
      winners increased in IGF-1 levels over losers or that members of the same team
      were more similar in IGF-1 levels than they were to players from other teams.
      These findings provide limited support toward the community effect in height
      hypothesis. The findings are discussed in relation to the action of the growth
      hormone/IGF-1 axis as a transducer of multiple bio-social influences into a
      coherent signal which allows the growing human to adjust and adapt to local
      ecological conditions. 

PMID- 25946189
TI  - Uvrag targeting by Mir125a and Mir351 modulates autophagy associated with Ewsr1
      deficiency.
AB  - The EWSR1 (EWS RNA-binding protein 1/Ewing Sarcoma Break Point Region 1) gene
      encodes a RNA/DNA binding protein that is ubiquitously expressed and involved in
      various cellular processes. EWSR1 deficiency leads to impairment of development
      and accelerated senescence but the mechanism is not known. Herein, we found that
      EWSR1 modulates the Uvrag (UV radiation resistance associated) gene at the post
      transcription level. Interestingly, EWSR1 deficiency led to the activation of the
      DROSHA-mediated microprocessor complex and increased the level of Mir125a and
      Mir351, which directly target Uvrag. Moreover, the Mir125a- and Mir351-mediated
      reduction of Uvrag was associated with the inhibition of autophagy that was
      confirmed in ewsr1 knockout (KO) MEFs and ewsr1 KO mice. Taken together, our data
      indicate that EWSR1 is involved in the post-transcriptional regulation of Uvrag
      via a miRNA-dependent pathway, resulting in the deregulation of autophagy
      inhibition. The mechanism of Uvrag and autophagy regulation by EWSR1 provides new
      insights into the role of EWSR1 deficiency-related cellular dysfunction. 

PMID- 25946191
TI  - Reduced CSF Water Influx in Alzheimer's Disease Supporting the beta-Amyloid
      Clearance Hypothesis.
AB  - OBJECTIVE: To investigate whether water influx into cerebrospinal fluid (CSF)
      space is reduced in Alzheimer's patients as previously shown in the transgenic
      mouse model for Alzheimer's disease. METHODS: Ten normal young volunteers (young
      control, 21-30 years old), ten normal senior volunteers (senior control, 60-78
      years old, MMSE >= 29), and ten Alzheimer's disease (AD) patients (study group,
      59-84 years old, MMSE: 13-19) participated in this study. All AD patients were
      diagnosed by neurologists specializing in dementia based on DSM-IV criteria. CSF
      dynamics were analyzed using positron emission tomography (PET) following an
      intravenous injection of 1,000 MBq [15O]H2O synthesized on-line. RESULTS: Water
      influx into CSF space in AD patients, expressed as influx ratio, (0.755 +/-
      0.089) was significantly reduced compared to young controls (1.357 +/- 0.185; p <
      0.001) and also compared to normal senior controls (0.981 +/- 0.253, p < 0.05).
      Influx ratio in normal senior controls was significantly reduced compared to
      young controls (p < 0.01). CONCLUSION: Water influx into the CSF is significantly
      reduced in AD patients. beta-amyloid clearance has been shown to be dependent on
      interstitial flow and CSF production. The current study indicates that reduction
      in water influx into the CSF may disturb the clearance rate of beta-amyloid, and
      therefore be linked to the pathogenesis of AD. TRIAL REGISTRATION: UMIN Clinical
      Trials Registry UMIN000011939.

PMID- 25946193
TI  - Scanning tunneling microscopy studies of low-dimensional materials: charge
      density wave pinning and melting in two dimensions.

PMID- 25946192
TI  - CRISPR Diversity in E. coli Isolates from Australian Animals, Humans and
      Environmental Waters.
AB  - Seventy four SNP genotypes and 54 E. coli genomes from kangaroo, Tasmanian devil,
      reptile, cattle, dog, horse, duck, bird, fish, rodent, human and environmental
      water sources were screened for the presence of the CRISPR 2.1 loci flanked by
      cas2 and iap genes. CRISPR 2.1 regions were found in 49% of the strains analysed.
      The majority of human E. coli isolates lacked the CRISPR 2.1 locus. We described
      76 CRISPR 2.1 positive isolates originating from Australian animals and humans,
      which contained a total of 764 spacer sequences. CRISPR arrays demonstrated a
      long history of phage attacks especially in isolates from birds (up to 40
      spacers). The most prevalent spacer (1.6%) was an ancient spacer found mainly in
      human, horse, duck, rodent, reptile and environmental water sources. The sequence
      of this spacer matched the intestinal P7 phage and the pO111 plasmid of E. coli. 

PMID- 25946194
TI  - The fishery performance indicators: a management tool for triple bottom line
      outcomes.
AB  - Pursuit of the triple bottom line of economic, community and ecological
      sustainability has increased the complexity of fishery management; fisheries
      assessments require new types of data and analysis to guide science-based policy
      in addition to traditional biological information and modeling. We introduce the
      Fishery Performance Indicators (FPIs), a broadly applicable and flexible tool for
      assessing performance in individual fisheries, and for establishing cross
      sectional links between enabling conditions, management strategies and triple
      bottom line outcomes. Conceptually separating measures of performance, the FPIs
      use 68 individual outcome metrics--coded on a 1 to 5 scale based on expert
      assessment to facilitate application to data poor fisheries and sectors--that can
      be partitioned into sector-based or triple-bottom-line sustainability-based
      interpretative indicators. Variation among outcomes is explained with 54
      similarly structured metrics of inputs, management approaches and enabling
      conditions. Using 61 initial fishery case studies drawn from industrial and
      developing countries around the world, we demonstrate the inferential importance
      of tracking economic and community outcomes, in addition to resource status.

PMID- 25946196
TI  - Does lower limb exercise worsen renal artery hemodynamics in patients with
      abdominal aortic aneurysm?
AB  - Renal artery stenosis (RAS) and renal complications emerge in some patients after
      endovascular aneurysm repair (EVAR) to treat abdominal aorta aneurysm (AAA). The
      mechanisms for the causes of these problems are not clear. We hypothesized that
      for EVAR patients, lower limb exercise could negatively influence the physiology
      of the renal artery and the renal function, by decreasing the blood flow velocity
      and changing the hemodynamics in the renal arteries. To evaluate this hypothesis,
      pre- and post-operative models of the abdominal aorta were reconstructed based on
      CT images. The hemodynamic environment was numerically simulated under rest and
      lower limb exercise conditions. The results revealed that in the renal arteries,
      lower limb exercise decreased the wall shear stress (WSS), increased the
      oscillatory shear index (OSI) and increased the relative residence time (RRT).
      EVAR further enhanced these effects. Because these parameters are related to
      artery stenosis and atherosclerosis, this preliminary study concluded that lower
      limb exercise may increase the potential risk of inducing renal artery stenosis
      and renal complications for AAA patients. This finding could help elucidate the
      mechanism of renal artery stenosis and renal complications after EVAR and warn us
      to reconsider the management and nursing care of AAA patients. 

PMID- 25946195
TI  - Viroporin Activity of the Foot-and-Mouth Disease Virus Non-Structural 2B Protein.
AB  - Viroporins are a family of low-molecular-weight hydrophobic transmembrane
      proteins that are encoded by various animal viruses. Viroporins form
      transmembrane pores in host cells via oligomerization, thereby destroying
      cellular homeostasis and inducing cytopathy for virus replication and virion
      release. Among the Picornaviridae family of viruses, the 2B protein encoded by
      enteroviruses is well understood, whereas the viroporin activity of the 2B
      protein encoded by the foot-and-mouth disease virus (FMDV) has not yet been
      described. An analysis of the FMDV 2B protein domains by computer-aided programs
      conducted in this study revealed that this protein may contain two transmembrane
      regions. Further biochemical, biophysical and functional studies revealed that
      the protein possesses a number of features typical of a viroporin when it is
      overexpressed in bacterial and mammalian cells as well as in FMDV-infected cells.
      The protein was found to be mainly localized in the endoplasmic reticulum (ER),
      with both the N- and C-terminal domains stretched into the cytosol. It exhibited
      cytotoxicity in Escherichia coli, which attenuated 2B protein expression. The
      release of virions from cells infected with FMDV was inhibited by amantadine, a
      viroporin inhibitor. The 2B protein monomers interacted with each other to form
      both intracellular and extracellular oligomers. The Ca(2+) concentration in the
      cells increased, and the integrity of the cytoplasmic membrane was disrupted in
      cells that expressed the 2B protein. Moreover, the 2B protein induced intense
      autophagy in host cells. All of the results of this study demonstrate that the
      FMDV 2B protein has properties that are also found in other viroporins and may be
      involved in the infection mechanism of FMDV.

PMID- 25946200
TI  - A Label-Free, Sensitive, Real-Time, Semiquantitative Electrochemical Measurement
      Method for DNA Polymerase Amplification (ePCR).
AB  - Oligonucleotide hybridization to a complementary sequence that is covalently
      attached to an electrochemically active conducting polymer (ECP) coating the
      working electrode of an electrochemical cell causes an increase in reaction
      impedance for the ferro-ferricyanide redox couple. We demonstrate the use of this
      effect to measure, in real time, the progress of DNA polymerase chain reaction
      (PCR) amplification of a minor component of a DNA extract. The forward primer is
      attached to the ECP. The solution contains other PCR components and the redox
      couple. Each cycle of amplification gives an easily measurable impedance
      increase. Target concentration can be estimated by cycle count to reach a
      threshold impedance. As proof of principle, we demonstrate an electrochemical
      real-time quantitative PCR (e-PCR) measurement in the total DNA extracted from
      chicken blood of an 844 base pair region of the mitochondrial Cytochrome c
      oxidase gene, present at ~1 ppm of total DNA. We show that the detection and
      semiquantitation of as few as 2 copies/MUL of target can be achieved within less
      than 10 PCR cycles. 

PMID- 25946197
TI  - Identification and Functional Analysis of a Novel MIP Gene Mutation Associated
      with Congenital Cataract in a Chinese Family.
AB  - Congenital cataracts are major cause of visual impairment and blindness in
      children and previous studies have shown about 1/3 of non-syndromic congenital
      cataracts are inherited. Major intrinsic protein of the lens (MIP), also known as
      AQP0, plays a critical role in transparency and development of the lens. To date,
      more than 10 mutations in MIP have been linked to hereditary cataracts in humans.
      In this study, we investigated the genetic and functional defects underlying a
      four-generation Chinese family affected with congenital progressive cortical
      punctate cataract. Mutation screening of the candidate genes revealed a missense
      mutation at position 448 (c.448G>C) of MIP, which resulted in the substitution of
      a conserved aspartic acid with histidine at codon 150 (p.D150H). By linkage and
      haplotype analysis, we obtained positive multipoint logarithm of odds (LOD)
      scores at microsatellite markers D12S1632 (Zmax = 1.804 at alpha = 1.000) and
      D12S1691 (Zmax = 1.806 at alpha = 1.000), which flanked the candidate locus. The
      prediction results of PolyPhen-2 and SIFT indicated that the p.D150H mutation was
      likely to damage to the structure and function of AQP0. The wild type and p.D150H
      mutant AQP0 were expressed in HeLa cells separately and the immunofluorescence
      results showed that the WT-AQP0 distributed at the plasma membrane and in
      cytoplasm, while AQP0-D150H failed to reach the plasma membrane and was mainly
      retained in the Golgi apparatus. Moreover, protein levels of AQP0-D150H were
      significantly lower than those of wide type AQP0 in membrane-enriched lysates
      when the HEK-293T cells were transfected with the same amount of wild type and
      mutant plasmids individually. Taken together, our data suggest the p.D150H
      mutation is a novel disease-causing mutation in MIP, which leads to congenital
      progressive cortical punctate cataract by impairing the trafficking mechanism of
      AQP0. 

PMID- 25946201
TI  - Implants, bone and soft tissues--An international update 2015.

PMID- 25946198
TI  - A high performing brain-machine interface driven by low-frequency local field
      potentials alone and together with spikes.
AB  - OBJECTIVE: Brain-machine interfaces (BMIs) seek to enable people with movement
      disabilities to directly control prosthetic systems with their neural activity.
      Current high performance BMIs are driven by action potentials (spikes), but
      access to this signal often diminishes as sensors degrade over time. Decoding
      local field potentials (LFPs) as an alternative or complementary BMI control
      signal may improve performance when there is a paucity of spike signals. To date
      only a small handful of LFP decoding methods have been tested online; there
      remains a need to test different LFP decoding approaches and improve LFP-driven
      performance. There has also not been a reported demonstration of a hybrid BMI
      that decodes kinematics from both LFP and spikes. Here we first evaluate a BMI
      driven by the local motor potential (LMP), a low-pass filtered time-domain LFP
      amplitude feature. We then combine decoding of both LMP and spikes to implement a
      hybrid BMI. APPROACH: Spikes and LFP were recorded from two macaques implanted
      with multielectrode arrays in primary and premotor cortex while they performed a
      reaching task. We then evaluated closed-loop BMI control using biomimetic
      decoders driven by LMP, spikes, or both signals together. MAIN RESULTS: LMP
      decoding enabled quick and accurate cursor control which surpassed previously
      reported LFP BMI performance. Hybrid decoding of both spikes and LMP improved
      performance when spikes signal quality was mediocre to poor. SIGNIFICANCE: These
      findings show that LMP is an effective BMI control signal which requires minimal
      power to extract and can substitute for or augment impoverished spikes signals.
      Use of this signal may lengthen the useful lifespan of BMIs and is therefore an
      important step towards clinically viable BMIs.

PMID- 25946203
TI  - Practical methylenation reaction for aldehydes and ketones using new Julia-type
      reagents.
AB  - A new Julia-type methylenation reagent, 1-methyl-2-(methylsulfonyl)benzimidazole
      (1e), reacts with a variety of aldehydes and ketones in the presence of either
      NaHMDS (-55  degrees C to rt) or t-BuOK (rt, 1 h) in DMF to give the
      corresponding terminal alkenes in high yields. The byproducts are easily removed,
      and the reaction conditions are mild and practical. 

PMID- 25946202
TI  - Nuclear PTEN tumor-suppressor functions through maintaining heterochromatin
      structure.
AB  - The tumor suppressor, PTEN, is one of the most commonly mutated genes in cancer.
      Recently, PTEN has been shown to localize in the nucleus and is required to
      maintain genomic stability. Here, we show that nuclear PTEN, independent of its
      phosphatase activity, is essential for maintaining heterochromatin structure.
      Depletion of PTEN leads to loss of heterochromatic foci, decreased chromatin
      compaction, overexpression of heterochromatic genes, and reduced protein
      stability of heterochromatin protein 1 alpha. We found that the C-terminus of
      PTEN is required to maintain heterochromatin structure. Additionally, cancer
      associated PTEN mutants lost their tumor-suppressor function when their
      heterochromatin structure was compromised. We propose that this novel role of
      PTEN accounts for its function in guarding genomic stability and suppressing
      tumor development. 

PMID- 25946204
TI  - Spatial patterns in markers of contaminant exposure, glucose and glycogen
      metabolism, and immunological response in juvenile winter flounder
      (Pseudoplueronectes americanus).
AB  - Inshore winter flounder (Pseudoplueronectes americanus) populations in NY, USA
      have reached record low numbers in recent years, and recruitment into the fishery
      appears to be limited by survival of post-settlement juvenile fish. In order to
      identify cellular pathways associated with site-specific variation in condition
      and mortality, we examined differential mRNA expression in juvenile winter
      flounder collected from six different bays across a gradient in human population
      density and sewage inputs. Illumina sequencing of pooled samples of flounder from
      contrasting degraded sites and less impacted sites was used to guide our choice
      of targets for qPCR analysis. 253 transcripts of >100bp were differentially
      expressed, with 60% showing strong homology to mostly teleost sequences within
      the NCBI database. Based on these data, transcripts representing nine genes of
      interest associated with contaminant exposure, immune response and glucose and
      glycogen metabolism were examined by qPCR in individual flounder from each site.
      Statistically significant site-specific differences were observed in expression
      of all but one gene, although patterns in expression were complex with only one
      (vitellogenin), demonstrating a west to east gradient consistent with known
      loadings of municipal sewage effluent. Principal components analysis (PCA)
      identified relationships among the genes evaluated. Our data indicate that
      juvenile winter flounder are responding to estrogenic chemicals in more urbanized
      coastal bays, and suggests potential mechanistic links between immune response,
      contaminant exposure and energy metabolism. 

PMID- 25946205
TI  - Variable Responses to Carbon Utilization between Planktonic and Biofilm Cells of
      a Human Carrier Strain of Salmonella enterica Serovar Typhi.
AB  - Salmonella enterica serovar Typhi (S. Typhi) is a foodborne pathogen that causes
      typhoid fever and infects only humans. The ability of S. Typhi to survive outside
      the human host remains unclear, particularly in human carrier strains. In this
      study, we have investigated the catabolic activity of a human carrier S. Typhi
      strain in both planktonic and biofilm cells using the high-throughput Biolog
      Phenotype MicroArray, Minimum Biofilm Eradication Concentration (MBEC) biofilm
      inoculator (96-well peg lid) and whole genome sequence data. Additional strains
      of S. Typhi were tested to further validate the variation of catabolism in
      selected carbon substrates in the different bacterial growth phases. The analyzes
      of the carbon utilization data indicated that planktonic cells of the carrier
      strain, S. Typhi CR0044 could utilize a broader range of carbon substrates
      compared to biofilm cells. Pyruvic acid and succinic acid which are related to
      energy metabolism were actively catabolised in the planktonic stage compared to
      biofilm stage. On the other hand, glycerol, L-fucose, L-rhamnose (carbohydrates)
      and D-threonine (amino acid) were more actively catabolised by biofilm cells
      compared to planktonic cells. Notably, dextrin and pectin could induce strong
      biofilm formation in the human carrier strain of S. Typhi. However, pectin could
      not induce formation of biofilm in the other S. Typhi strains. Phenome data
      showed the utilization of certain carbon substrates which was supported by the
      presence of the catabolism-associated genes in S. Typhi CR0044. In conclusion,
      the findings showed the differential carbon utilization between planktonic and
      biofilm cells of a S. Typhi human carrier strain. The differences found in the
      carbon utilization profiles suggested that S. Typhi uses substrates mainly found
      in the human biliary mucus glycoprotein, gallbladder, liver and cortex of the
      kidney of the human host. The observed diversity in the carbon catabolism
      profiles among different S. Typhi strains has suggested the possible involvement
      of various metabolic pathways that might be related to the virulence and
      pathogenesis of this host-restricted human pathogen. The data serve as a caveat
      for future in-vivo studies to investigate the carbon metabolic activity to the
      pathogenesis of S. Typhi. 

PMID- 25946207
TI  - Selective vs Nonselective Nonsteroidal Anti-inflammatory Drugs and Anastomotic
      Leakage After Colorectal Surgery-Reply.

PMID- 25946206
TI  - Catecholamine metabolism in paraganglioma and pheochromocytoma: similar tumors in
      different sites?
AB  - Pheochromocytoma (PHEO) and paraganglioma (PGL) are catecholamine-producing
      neuroendocrine tumors that arise respectively inside or outside the adrenal
      medulla. Several reports have shown that adrenal glucocorticoids (GC) play an
      important regulatory role on the genes encoding the main enzymes involved in
      catecholamine (CAT) synthesis i.e. tyrosine hydroxylase (TH), dopamine beta
      hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT). To assess
      the influence of tumor location on CAT metabolism, 66 tissue samples (53 PHEO, 13
      PGL) and 73 plasma samples (50 PHEO, 23 PGL) were studied. Western blot and qPCR
      were performed for TH, DBH and PNMT expression. We found a significantly lower
      intra-tumoral concentration of CAT and metanephrines (MNs) in PGL along with a
      downregulation of TH and PNMT at both mRNA and protein level compared with PHEO.
      However, when PHEO were partitioned into noradrenergic (NorAd) and mixed tumors
      based on an intra-tumoral CAT ratio (NE/E >90%), PGL and NorAd PHEO sustained
      similar TH, DBH and PNMT gene and protein expression. CAT concentration and
      composition were also similar between NorAd PHEO and PGL, excluding the use of
      CAT or MNs to discriminate between PGL and PHEO on the basis of biochemical
      tests. We observed an increase of TH mRNA concentration without correlation with
      TH protein expression in primary cell culture of PHEO and PGL incubated with
      dexamethasone during 24 hours; no changes were monitored for PNMT and DBH at both
      mRNA and protein level in PHEO and PGL. Altogether, these results indicate that
      long term CAT synthesis is not driven by the close environment where the tumor
      develops and suggest that GC alone is not sufficient to regulate CAT synthesis
      pathway in PHEO/PGL. 

PMID- 25946208
TI  - A Genetically Encoded FRET Probe to Detect Intranucleosomal Histone H3K9 or H3K14
      Acetylation Using BRD4, a BET Family Member.
AB  - Acetylation is a well-characterized histone modification, which plays important
      roles in controlling epigenetic gene expression, and its malfunction is tightly
      associated with cancer. By taking advantage of the specific binding of BRD4 to
      acetylated lysine residues, we developed a FRET-based probe for visualizing
      histone H3 acetylation in living cells. BRD4, a protein known to be involved in
      acute myeloid leukemia and nuclear protein in testis midline carcinoma,
      recognizes the acetylation of histone H3 via its bromodomains. The probe
      exhibited a significant change in FRET signaling that was dependent on histone H3
      acetylation. Mutagenesis studies revealed that an increase in the emission ratio
      reflected the acetylation of either K9 or K14 of histone H3 within the probe.
      Since BRD4 has increasingly drawn attention as a new anticancer drug target, we
      demonstrated that the developed fluorescent probe will also serve as a powerful
      tool to evaluate BRD4 inhibitors in living cells. 

PMID- 25946209
TI  - High mean water vapour pressure promotes the transmission of bacillary dysentery.
AB  - Bacillary dysentery is an infectious disease caused by Shigella dysenteriae,
      which has a seasonal distribution. External environmental factors, including
      climate, play a significant role in its transmission. This paper identifies
      climate-related risk factors and their role in bacillary dysentery transmission.
      Harbin, in northeast China, with a temperate climate, and Quzhou, in southern
      China, with a subtropical climate, are chosen as the study locations. The least
      absolute shrinkage and selectionator operator is applied to select relevant
      climate factors involved in the transmission of bacillary dysentery. Based on the
      selected relevant climate factors and incidence rates, an AutoRegressive
      Integrated Moving Average (ARIMA) model is established successfully as a time
      series prediction model. The numerical results demonstrate that the mean water
      vapour pressure over the previous month results in a high relative risk for
      bacillary dysentery transmission in both cities, and the ARIMA model can
      successfully perform such a prediction. These results provide better explanations
      for the relationship between climate factors and bacillary dysentery transmission
      than those put forth in other studies that use only correlation coefficients or
      fitting models. The findings in this paper demonstrate that the mean water vapour
      pressure over the previous month is an important predictor for the transmission
      of bacillary dysentery. 

PMID- 25946210
TI  - Efficacy of different modes of fractional CO2 laser in the treatment of primary
      cutaneous amyloidosis: A randomized clinical trial.
AB  - BACKGROUND: Primary cutaneous amyloidosis (PCA) comprises three main forms:
      macular, lichen, and nodular amyloidosis. The current available treatments are
      quite disappointing. OBJECTIVES: Assess and compare the clinical and histological
      changes induced by different modes of Fractional CO2 laser in treatment of PCA.
      PATIENTS AND METHODS: Twenty five patients with PCA (16 macular and 9 lichen
      amyloidosis) were treated by fractional CO2 using; superficial ablation (area A)
      and deep rejuvenation (area B). Each patient received 4 sessions with 4 weeks
      intervals. Skin biopsies were obtained from all patients at baseline and one
      month after the last session. Patients were assessed clinically and
      histologically (Congo red staining, polarized light). Patients were followed-up
      for 3 months after treatment. RESULTS: Both modes yielded significant reduction
      of pigmentation, thickness, itching, and amyloid deposits (P-value < 0.001).
      However, the percentage of reduction of pigmentation was significantly higher in
      area A (P-value = 0.003). Pain was significantly higher in area B. Significant
      reduction in dermal amyloid deposits denotes their trans-epidermal elimination
      induced by fractional photothermolysis. CONCLUSION: Both superficial and deep
      modes of fractional CO2 laser showed comparable efficacy in treatment of PCA.
      Superficial mode being better tolerated by patients, is recommended as a valid
      therapeutic option.

PMID- 25946213
TI  - New treatments highlighted for lymphoma and multiple myeloma.

PMID- 25946212
TI  - Failure rate: Why many cancer drugs don't receive FDA approval, and what can be
      done about it.

PMID- 25946214
TI  - Smoking still causes significant number of cancer deaths.

PMID- 25946211
TI  - Comparison of genetic and epigenetic alterations of primary tumors and matched
      plasma samples in patients with colorectal cancer.
AB  - BACKGROUND: Although recent advances in circulating DNA analysis allow the
      prediction of tumor genomes by noninvasive means, some challenges remain, which
      limit the widespread introduction of cfDNA in cancer diagnostics. We analyzed the
      status of the two best characterized colorectal cancer (CRC) genetic and
      epigenetic alterations in a cohort of CRC patients, and then compared the degree
      to which the two patterns move from tissue to plasma in order to improve our
      understanding of biology modulating the concordance between tissues and plasma
      methylation and mutation profiles. METHODS: Plasma and tumor tissues were
      collected from 85 patients (69+/-14 years, 56 males). KRAS and SEPT9 status was
      assessed by allele refractory mutation system quantitative PCR and quantitative
      methylation-specific PCR, respectively. Six of the most common point mutations at
      codon 12 and 13 were investigated for KRAS analysis. RESULTS: KRAS mutations and
      SEPT9 promoter methylation were present in 34% (29/85) and in 82% (70/85) of
      primary tumor tissue samples. Both genetic and epigenetic analyses of cfDNA
      revealed a high overall concordance and specificity compared with tumor-tissue
      analyses. Patients presenting with both genetic and epigenetic alterations in
      tissue specimens (31.8%, 27/85) were considered for further analyses. The median
      methylation rates in tumour tissues and plasma samples were 64.5% (12.2-99.8%)
      and 14.5% (0-45.5%), respectively. The median KRAS mutation load (for matched
      mutations) was 33.6% (1.8-86.3%) in tissues and 2.9% (0-17.3) in plasma samples.
      The plasma/tissue (p/t) ratio of SEPT9 methylation rate was significantly higher
      than the p/t ratio of KRAS mutation load, especially in early stage cancers
      (p=0.0108). CONCLUSION: The results of this study show a discrepant rate of
      epigenetic vs. genetic alterations moving from tissue to plasma. Many factors
      could affect mutation cfDNA analysis, including both presence of tumor clonal
      heterogeneity and strict compartmentalization of KRAS mutation profile. The
      present study highlights the importance of considering the nature of the
      alteration when analyzing tumor-derived cfDNA.

PMID- 25946216
TI  - Phylogenetic and Taxonomic Revision of an Enigmatic Group of Haptorian Ciliates,
      with Establishment of the Kentrophyllidae fam. n. (Protozoa, Ciliophora,
      Litostomatea, Pleurostomatida).
AB  - Haptorian ciliates in the closely similar genera Kentrophyllum and Epiphyllum
      possess a unique pattern of ciliature and are distinguished from one another only
      by the presence or absence of cytoplasmic spines projecting from the margin of
      the cell. Phylogenetic analyses based on SSU rDNA sequences of three new samples
      from coastal habitats in China revealed that species in the two genera clustered
      together indiscriminately (i.e. forms of neither genus clustered into an
      independent clade) as a maximally supported, monophyletic clade that branches
      basally to all other clades in the order Pleurostomatida and is strongly
      divergent from other members of the family in which the genera have been placed.
      As a result, we propose that Epiphyllum be synonymized with Kentrophyllum and
      that a new family Kentrophyllidae fam. n. be established for the genus. We
      hypothesize that the two-sutures of Kentrophyllum is a plesiomorphy within the
      Pleurostomatida and the unique peripheral kinety might represent an autapomorphy
      of Kentrophyllum. In addition, we provide a taxonomic revision of Kentrophyllum
      including description of three new species (K. bispinum sp. n., K. strumosum sp.
      n., and K. qingdaoense sp. n.), redescription of K. verrucosum (Stokes, 1893)
      Petz et al., 1995, and three new combinations (K. soliforme (Faure-Fremiet, 1908)
      comb. n., K. hohuensis (Wang and Nie, 1933) comb. n. and K. shenzhenense (Pan et
      al., 2010) comb. n.). The surface ultrastructure of the genus Kentrophyllum is
      recorded for the first time. And a key to all known species of Kentrophyllum was
      also suggested. 

PMID- 25946218
TI  - Correction: Shared dosimetry error in epidemiological dose-response analyses.

PMID- 25946217
TI  - Evolutionary History of the Live-Bearing Endemic Allotoca diazi Species Complex
      (Actinopterygii, Goodeinae): Evidence of Founder Effect Events in the Mexican Pre
      Hispanic Period.
AB  - The evolutionary history of Mexican ichthyofauna has been strongly linked to
      natural events, and the impact of pre-Hispanic cultures is little known. The live
      bearing fish species Allotoca diazi, Allotoca meeki and Allotoca catarinae occur
      in areas of biological, cultural and economic importance in central Mexico:
      Patzcuaro basin, Zirahuen basin, and the Cupatitzio River, respectively. The
      species are closely related genetically and morphologically, and hypotheses have
      attempted to explain their systematics and biogeography. Mitochondrial DNA and
      microsatellite markers were used to investigate the evolutionary history of the
      complex. The species complex shows minimal genetic differentiation. The
      separation of A. diazi and A. meeki was dated to 400-7000 years ago, explained by
      geological and climate events. A bottleneck and reduction of genetic diversity in
      Allotoca diazi was detected, attributed to recent climate fluctuations and
      anthropogenic activity. The isolation of A. catarinae occurred ~1900 years ago.
      No geological events are documented in the area during this period, but the date
      is contemporary with P'urhepecha culture settlements. This founder effect
      represents the first evidence of fish species translocation by a pre-Hispanic
      culture of Mexico. The response of the complex to climate fluctuation, geological
      changes and human activity in the past and the future according to the ecological
      niches predictions indicates areas of vulnerability and important information for
      conservation. The new genetic information showed that the Allotoca diazi complex
      consist of two genetic groups with an incomplete lineage sorting pattern:
      Patzcuaro and Zirahuen lakes, and an introduced population in the Cupatitzio
      River. 

PMID- 25946219
TI  - Lutein and lutein esters in whole grain flours made from 75 genotypes of 5
      triticum species grown at multiple sites.
AB  - Concentrations of lutein and lutein esters were determined in an ample collection
      of 75 wheat genotypes comprising bread wheat (Triticum aestivum L.), durum
      (Triticum durum Desf.), spelt (Triticum spelta L.), emmer (Triticum dicoccum
      Schrank), and einkorn (Triticum monococcum L.) grown in five different
      environments. Einkorn genotypes showed the highest total amounts of lutein (4.5
      7.8 MUg/g dry matter), followed by durum (2.0-4.6 MUg/g), spelt (0.9-2.0 MUg/g),
      emmer (0.8-1.9 MUg/g), and bread wheat (0.7-2.0 MUg/g). Due to the observed
      highly significant genetic variance and high heritability, lutein contents of
      wheat genotypes may be increased by future plant breeding. Detailed HPLC-DAD
      APCI(+/-)-MS(n) data allowing the identification of six lutein monoesters and
      nine diesters are presented. Linoleic, palmitic, and oleic acids were the most
      abundant fatty acids in both the lutein esters and total free lipid fractions.
      Lutein esters were virtually absent in the tetraploid durum and emmer species,
      whereas their concentrations considerably differed among the genotypes belonging
      to the other species. 

PMID- 25946220
TI  - New gel-like polymers as selective weak-base anion exchangers.
AB  - A group of new anion exchangers, based on polyamine podands and of excellent ion
      binding capacity, were synthesized. The materials were obtained in reactions
      between various poly(ethyleneamines) with glycidyl derivatives of
      cyclotetrasiloxane. The final polymeric, strongly cross-linked materials form gel
      like solids. Their structures and interactions with anions adsorbed were studied
      by spectroscopic methods (CP-MAS NMR, FR-IR, UV-Vis). The sorption isotherms and
      kinetic parameters were determined for 29 anions. Materials studied show high ion
      capacity and selectivity towards some important anions, e.g., selenate(VI) or
      perrhenate. 

PMID- 25946221
TI  - Damaging the Integrated HIV Proviral DNA with TALENs.
AB  - HIV-1 integrates its proviral DNA genome into the host genome, presenting
      barriers for virus eradication. Several new gene-editing technologies have
      emerged that could potentially be used to damage integrated proviral DNA. In this
      study, we use transcription activator-like effector nucleases (TALENs) to target
      a highly conserved sequence in the transactivation response element (TAR) of the
      HIV-1 proviral DNA. We demonstrated that TALENs cleave a DNA template with the
      HIV-1 proviral target site in vitro. A GFP reporter, under control of HIV-1 TAR,
      was efficiently inactivated by mutations introduced by transfection of TALEN
      plasmids. When infected cells containing the full-length integrated HIV-1
      proviral DNA were transfected with TALENs, the TAR region accumulated indels.
      When one of these mutants was tested, the mutated HIV-1 proviral DNA was
      incapable of producing detectable Gag expression. TALEN variants engineered for
      degenerate recognition of select nucleotide positions also cleaved proviral DNA
      in vitro and the full-length integrated proviral DNA genome in living cells.
      These results suggest a possible design strategy for the therapeutic
      considerations of incomplete target sequence conservation and acquired resistance
      mutations. We have established a new strategy for damaging integrated HIV
      proviral DNA that may have future potential for HIV-1 proviral DNA eradication. 

PMID- 25946222
TI  - Can we improve structured sequence processing? Exploring the direct and indirect
      effects of computerized training using a mediational model.
AB  - Recent research suggests that language acquisition may rely on domain-general
      learning abilities, such as structured sequence processing, which is the ability
      to extract, encode, and represent structured patterns in a temporal sequence. If
      structured sequence processing supports language, then it may be possible to
      improve language function by enhancing this foundational learning ability. The
      goal of the present study was to use a novel computerized training task as a
      means to better understand the relationship between structured sequence
      processing and language function. Participants first were assessed on pre
      training tasks to provide baseline behavioral measures of structured sequence
      processing and language abilities. Participants were then quasi-randomly assigned
      to either a treatment group involving adaptive structured visuospatial sequence
      training, a treatment group involving adaptive non-structured visuospatial
      sequence training, or a control group. Following four days of sequence training,
      all participants were assessed with the same pre-training measures. Overall
      comparison of the post-training means revealed no group differences. However, in
      order to examine the potential relations between sequence training, structured
      sequence processing, and language ability, we used a mediation analysis that
      showed two competing effects. In the indirect effect, adaptive sequence training
      with structural regularities had a positive impact on structured sequence
      processing performance, which in turn had a positive impact on language
      processing. This finding not only identifies a potential novel intervention to
      treat language impairments but also may be the first demonstration that
      structured sequence processing can be improved and that this, in turn, has an
      impact on language processing. However, in the direct effect, adaptive sequence
      training with structural regularities had a direct negative impact on language
      processing. This unexpected finding suggests that adaptive training with
      structural regularities might potentially interfere with language processing.
      Taken together, these findings underscore the importance of pursuing designs that
      promote a better understanding of the mechanisms underlying training-related
      changes, so that regimens can be developed that help reduce these types of
      negative effects while simultaneously maximizing the benefits to outcome measures
      of interest. 

PMID- 25946224
TI  - Generalized causal measure: the beauty lies in its generality.

PMID- 25946223
TI  - Evidence for Positive Selection within the PgiC1 Locus in the Grass Festuca
      ovina.
AB  - The dimeric metabolic enzyme phosphoglucose isomerase (PGI, EC 5.3.1.9) plays an
      essential role in energy production. In the grass Festuca ovina, field surveys of
      enzyme variation suggest that genetic variation at cytosolic PGI (PGIC) may be
      adaptively important. In the present study, we investigated the molecular basis
      of the potential adaptive significance of PGIC in F. ovina by analyzing cDNA
      sequence variation within the PgiC1 gene. Two, complementary, types of selection
      test both identified PGIC1 codon (amino acid) sites 200 and 173 as candidate
      targets of positive selection. Both candidate sites involve charge-changing amino
      acid polymorphisms. On the homology-modeled F. ovina PGIC1 3-D protein structure,
      the two candidate sites are located on the edge of either the inter-monomer
      boundary or the inter-domain cleft; examination of the homology-modeled PGIC1
      structure suggests that the amino acid changes at the two candidate sites are
      likely to influence the inter-monomer interaction or the domain-domain packing.
      Biochemical studies in humans have shown that mutations at several amino acid
      sites that are located close to the candidate sites in F. ovina, at the inter
      monomer boundary or the inter-domain cleft, can significantly change the
      stability and/or kinetic properties of the PGI enzyme. Molecular evolutionary
      studies in a wide range of other organisms suggest that PGI amino acid sites with
      similar locations to those of the candidate sites in F. ovina may be the targets
      of positive/balancing selection. Candidate sites 200 and 173 are the only sites
      that appear to discriminate between the two most common PGIC enzyme electromorphs
      in F. ovina: earlier studies suggest that these electromorphs are implicated in
      local adaptation to different grassland microhabitats. Our results suggest that
      PGIC1 sites 200 and 173 are under positive selection in F. ovina. 

PMID- 25946225
TI  - Using Twitter to survey alcohol use in the San Francisco Bay Area.

PMID- 25946226
TI  - Rejoinder.

PMID- 25946227
TI  - A general, multivariate definition of causal effects in epidemiology.
AB  - Population causal effects are often defined as contrasts of average individual
      level counterfactual outcomes, comparing different exposure levels. Common
      examples include causal risk difference and risk ratios. These and most other
      examples emphasize effects on disease onset, a reflection of the usual
      epidemiological interest in disease occurrence. Exposure effects on other health
      characteristics, such as prevalence or conditional risk of a particular
      disability, can be important as well, but contrasts involving these other
      measures may often be dismissed as non-causal. For example, an observed
      prevalence ratio might often viewed as an estimator of a causal incidence ratio
      and hence subject to bias. In this manuscript, we provide and evaluate a
      definition of causal effects that generalizes those previously available. A key
      part of the generalization is that contrasts used in the definition can involve
      multivariate, counterfactual outcomes, rather than only univariate outcomes. An
      important consequence of our generalization is that, using it, one can properly
      define causal effects based on a wide variety of additional measures. Examples
      include causal prevalence ratios and differences and causal conditional risk
      ratios and differences. We illustrate how these additional measures can be
      useful, natural, easily estimated, and of public health importance. Furthermore,
      we discuss conditions for valid estimation of each type of causal effect, and how
      improper interpretation or inferences for the wrong target population can be
      sources of bias. 

PMID- 25946228
TI  - Genetic aspects and clinical characteristics of familial Meniere's disease in a
      South Korean population.
AB  - OBJECTIVES/HYPOTHESIS: This study was undertaken to investigate the prevalence,
      inheritance patterns, and clinical characteristics of familial Meniere's disease
      (MD) in a South Korean population. STUDY DESIGN: Direct interviews, telephone
      interviews, and reviews of the medical records of definite Meniere's disease
      patients and their families. METHODS: Direct and telephone interviews were
      performed for 286 definite MD patients and their family members who were
      suspected of having MD. The diagnosis of MD in family members was made by
      obtaining a detailed history, performing basic neurotological examinations and
      reviewing hearing test results. The clinical characteristics as well as the
      prevalence and inheritance patterns of familial MD were analyzed. RESULTS: The
      prevalence of familial Meniere-like syndrome (at least one family member with
      definite MD and other members with probable MD) and definite familial MD (two or
      more family members with definite Meniere's disease) were 9.8% and 6.3%,
      respectively, and the most common inheritance pattern was autosomal dominant with
      incomplete penetrance. The significant clinical characteristics of familial cases
      were an early disease onset and a higher prevalence of migraines. CONCLUSIONS:
      This is the first report describing the genetic aspects of MD in a single large
      Asian population. The prevalence of definite familial MD was 6.3% with an
      incomplete autosomal dominant inheritance pattern in most cases. Early-onset age
      and a high prevalence of migraines were significant clinical features of familial
      MD in this South Korean population. These data could provide a basis for the
      analysis of the genetic mechanism of familial MD in Asian populations. LEVEL OF
      EVIDENCE: 4.

PMID- 25946229
TI  - Surface Modified Biodegradable Electrospun Membranes as a Carrier for Human
      Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells.
AB  - Human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cells are
      currently undergoing clinical trials to treat retinal degenerative diseases.
      Transplantation of hESC-RPE cells in conjuction with a supportive biomaterial
      carrier holds great potential as a future treatment for retinal degeneration.
      However, there has been no such biodegradable material that could support the
      growth and maturation of hESC-RPE cells so far. The primary aim of this work was
      to create a thin porous poly (L-lactide-co-caprolactone) (PLCL) membrane that
      could promote attachment, proliferation, and maturation of the hESC-RPE cells in
      serum-free culture conditions. The PLCL membranes were modified by atmospheric
      pressure plasma processing and coated with collagen IV to enhance cell growth and
      maturation. Permeability of the membranes was analyzed with an Ussing chamber
      system. Analysis with scanning electron microscopy, contact angle measurement,
      atomic force microscopy, and X-ray photoelectron spectroscopy demonstrated that
      plasma surface treatment augments the surface properties of the membrane, which
      enhances the binding and conformation of the protein. Cell proliferation assays,
      reverse transcription-polymerase chain reaction, indirect immunofluoresence
      staining, trans-epithelial electrical resistance measurements, and in vitro
      phagocytosis assay clearly demonstrated that the plasma treated PLCL membranes
      supported the adherence, proliferation, maturation and functionality of hESC-RPE
      cells in serum-free culture conditions. Here, we report for the first time, how
      PLCL membranes can be modified with atmospheric pressure plasma processing to
      enable the formation of a functional hESC-RPE monolayer on a porous biodegradable
      substrate, which have a potential as a tissue-engineered construct for
      regenerative retinal repair applications. 

PMID- 25946230
TI  - The Secreted Form of Transmembrane Protein 98 Promotes the Differentiation of T
      Helper 1 Cells.
AB  - Cytokines mediate the interaction of immune cells. Discovery of novel potential
      cytokines is of great value for both basic research and clinical application. In
      this study, we identified a novel immune-related molecule, transmembrane protein
      98 (TMEM98), through a high-throughput screening platform for novel potential
      cytokines at a genome-wide level using the strategy of immunogenomics. So far,
      there is no characteristic and immune-related functional report about it. In this
      study, we demonstrate that TMEM98 exists as a type II transmembrane protein both
      in the ectopically and endogenously expressed systems. Interestingly, TMEM98
      could also be secreted through exosomes. Moreover, the native secreted form of
      TMEM98 could be detected in the supernatants of activated human peripheral blood
      mononuclear cells and mouse CD4(+) T cells. Further expression profile analysis
      showed TMEM98 was upregulated during the activation and differentiation of T
      helper (Th) 1 cells. Function analysis showed that eukaryotic recombinant TMEM98
      (rTMEM98) promoted the differentiation of Th1 cells under both antigen
      nonspecific and antigen-specific Th1-skewing conditions. These findings were
      further confirmed in vivo as prokaryotic rTMEM98 administration significantly
      increased antigen-specific IFN-gamma production and serum antigen-specific IgG2a
      in the methylated bovine serum albumin-induced delayed-type hypersensitivity
      model. Overall, these observations emphasize the characteristics and essential
      roles of TMEM98 for the first time and will be helpful in further understanding
      the development of Th1 cells. 

PMID- 25946231
TI  - Progressive multifocal leukoencephalopathy: Dot-shaped inclusions and virus-host
      interactions.
AB  - Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease
      caused by reactivation of the asymptomatic persistent pathogen human polyomavirus
      JC (JC virus). The pathology of affected brain tissues demonstrates
      oligodendroglia-like cells with viral inclusions in their enlarged nuclei, a
      diagnostic hallmark of this disease. Today, the pathological features of this
      disease are expanding, partly due to an unsteady balance between viral virulence
      and host immunity. Intranuclear viral inclusions were initially thought to be
      amphophilic materials comprising the entire enlarged nucleus, based on HE
      staining (full inclusions). Howevewr, recent immunohistochemical analyses
      detected the presence of intranuclear viral inclusions in dots (dot-shaped
      inclusions). The dot-shaped inclusions reflect clustered progeny virions at
      punctuated subnuclear domains called promyelocytic leukemia nuclear bodies, and
      are indicative of early-stage viral infection or suppressed viral proliferation.
      Second, the JC virus is usually reactivated in patients with impaired immunity,
      and therefore the inflammatory reactions are poor. However, the causes of
      immunosuppression are divergent, as seen with the frequent use of
      immunosuppressive drugs, including natalizumab. Therefore, the degree of host
      immunity is variable; some patients show marked anti-viral inflammatory reactions
      and a good prognosis, indicating that a strong resistance against viral infection
      remains. Recovery of the immune system may also induce paradoxical clinical
      worsening, known as immune reconstitution inflammatory syndrome, the mechanism of
      which has not been clarified. The virus-host interactions have increased in
      complexity, and the pathology of PML is diverging. In this review, the pathology
      of PML will be described, with a focus on the intranuclear target of JC virus
      infection and host inflammatory reactions. 

PMID- 25946232
TI  - Clopidogrel response variability: impact of genetic polymorphism and platelet
      biomarkers for predicting adverse outcomes poststenting.
AB  - The aim of this study was to triage platelet reactivity and adverse vascular
      outcomes after dual antiplatelet therapy due to percutaneous coronary
      intervention (PCI) dependent on CYP2C19*2 and CYP2C19*3 genotypes in patients
      with coronary artery disease. Fifty-five patients with coronary artery disease
      were studied serially pre-PCI and post-PCI. Platelet reactivity was assessed by
      conventional light transmission aggregometry, VerifyNow Analyzer, and
      thromboelastography with platelet mapping. Genetic testing was performed with
      allele-specific real-time polymerase chain reaction. Adverse events included
      vascular death, acute myocardial infarction, repeated PCI, definite stent
      thrombosis, and angina recurrence. The common genotype (GG) was found in 39
      patients, heterozygous polymorphism CYP2C19 (GA) G681A allele was detected in 14
      patients, and the rare homozygous polymorphism CYP2C19 (AA) G681A allele was
      exhibited in 2 patients. There were no CYP2C19*3 (Trp212Ter) carriers among index
      patients. The platelet reactivity was higher in patients with heterozygous and
      homozygous carriers compared with GG genotype. The largest differences were
      observed among GG, GA, and AA genotypes, which correlated with the average values
      of platelet aggregation (P = 0.02). There was a significant link between adverse
      events and high platelet reactivity assessed by light transmission aggregometry
      (P = 0.002). We found a trend between different genotype and VerifyNow readings
      (P = 0.057); moreover, their cumulative impact on adverse events was significant
      (P = 0.041). Platelet reactivity is higher in patients with heterozygous and
      homozygous carriers of CYP2C19*2 versus common genotype and may predict an
      increased risk of clopidogrel response variability and/or experiencing adverse
      cardiac events. 

PMID- 25946233
TI  - Risk-Based Decision Making for Reoccupation of Contaminated Areas Following a
      Wide-Area Anthrax Release.
AB  - This article presents an analysis of postattack response strategies to mitigate
      the risks of reoccupying contaminated areas following a release of Bacillus
      anthracis spores (the bacterium responsible for causing anthrax) in an urban
      setting. The analysis is based on a hypothetical attack scenario in which
      individuals are exposed to B. anthracis spores during an initial aerosol release
      and then placed on prophylactic antibiotics that successfully protect them
      against the initial aerosol exposure. The risk from reoccupying buildings
      contaminated with spores due to their reaerosolization and inhalation is then
      evaluated. The response options considered include: decontamination of the
      buildings, vaccination of individuals reoccupying the buildings, extended
      evacuation of individuals from the contaminated buildings, and combinations of
      these options. The study uses a decision tree to estimate the costs and benefits
      of alternative response strategies across a range of exposure risks. Results for
      best estimates of model inputs suggest that the most cost-effective response for
      high-risk scenarios (individual chance of infection exceeding 11%) consists of
      evacuation and building decontamination. For infection risks between 4% and 11%,
      the preferred option is to evacuate for a short period, vaccinate, and then
      reoccupy once the vaccine has taken effect. For risks between 0.003% and 4%, the
      preferred option is to vaccinate only. For risks below 0.003%, none of the
      mitigation actions have positive expected monetary benefits. A sensitivity
      analysis indicates that for high-infection-likelihood scenarios, vaccination is
      recommended in the case where decontamination efficacy is less than 99.99%. 

PMID- 25946234
TI  - Retraction. Chemical constituents: water-soluble vitamins, free amino acids and
      sugar profile from Ganoderma adspersum.

PMID- 25946235
TI  - Ultrafast high-resolution magic-angle-spinning NMR spectroscopy.
AB  - We demonstrate the acquisition of ultrafast 2D NMR spectra of semi-solid samples,
      with a high-resolution magic-angle-spinning setup. Using a recent double-quantum
      NMR pulse sequence in optimised synchronisation conditions, high-quality 2D
      spectra can be recorded for a sample under magic-angle spinning. An illustration
      is given with a semi-solid sample of banana pulp. 

PMID- 25946236
TI  - Use of continuous positive airway pressure after rhinoplasty, septoplasty, and
      sinus surgery: A survey of current practice patterns.
AB  - OBJECTIVE: To explore current practice patterns in the use of continuous positive
      airway pressure (CPAP) following nasal or sinus surgery. STUDY DESIGN: Cross
      sectional survey. METHODS: An electronic 24-question survey was created to
      evaluate surgeon practice patterns for restarting CPAP after nasal surgery. We
      also explored factors contributing to their decisions (1-5 Likert scale) and
      complications believed to be directly related to restarting CPAP. Factors with a
      median rating score greater than 3 out of 5 were deemed "important." Subgroup
      analyses were performed to assess the impact of practice setting and clinical
      experience. RESULTS: A total of 407 physicians completed the survey (27.4%
      response rate for those that opened the e-mail). The majority of surgeons
      temporarily stop CPAP after nasal surgery, generally for 1 to 2 weeks, although
      the range of time is wide. There are also many surgeons who do not stop CPAP
      after any of these procedures and who reported that complications were fairly
      minimal. Severity of obstructive sleep apnea (OSA) was deemed important for all
      procedures. There were additional patient and surgery-specific factors considered
      important for each individual surgery. Subgroup analysis revealed significant
      differences in physician practice setting and clinical experience. CONCLUSION:
      Regarding the use of CPAP after nasal surgery, considerable variation existed in
      the practice patterns of physicians. Severity of OSA was universally considered
      important, but the remaining factors were less consistent. A comparative study
      investigating the outcomes of various protocols is necessary. LEVEL OF EVIDENCE:
      N/A.

PMID- 25946237
TI  - Multi-input distributed classifiers for synthetic genetic circuits.
AB  - For practical construction of complex synthetic genetic networks able to perform
      elaborate functions it is important to have a pool of relatively simple modules
      with different functionality which can be compounded together. To complement
      engineering of very different existing synthetic genetic devices such as
      switches, oscillators or logical gates, we propose and develop here a design of
      synthetic multi-input classifier based on a recently introduced distributed
      classifier concept. A heterogeneous population of cells acts as a single
      classifier, whose output is obtained by summarizing the outputs of individual
      cells. The learning ability is achieved by pruning the population, instead of
      tuning parameters of an individual cell. The present paper is focused on
      evaluating two possible schemes of multi-input gene classifier circuits. We
      demonstrate their suitability for implementing a multi-input distributed
      classifier capable of separating data which are inseparable for single-input
      classifiers, and characterize performance of the classifiers by analytical and
      numerical results. The simpler scheme implements a linear classifier in a single
      cell and is targeted at separable classification problems with simple class
      borders. A hard learning strategy is used to train a distributed classifier by
      removing from the population any cell answering incorrectly to at least one
      training example. The other scheme implements a circuit with a bell-shaped
      response in a single cell to allow potentially arbitrary shape of the
      classification border in the input space of a distributed classifier. Inseparable
      classification problems are addressed using soft learning strategy, characterized
      by probabilistic decision to keep or discard a cell at each training iteration.
      We expect that our classifier design contributes to the development of robust and
      predictable synthetic biosensors, which have the potential to affect applications
      in a lot of fields, including that of medicine and industry. 

PMID- 25946238
TI  - Accuracy of mucocutaneous leishmaniasis diagnosis using polymerase chain
      reaction: systematic literature review and meta-analysis.
AB  - The diagnosis of mucocutaneous leishmaniasis (MCL) is hampered by the absence of
      a gold standard. An accurate diagnosis is essential because of the high toxicity
      of the medications for the disease. This study aimed to assess the ability of
      polymerase chain reaction (PCR) to identify MCL and to compare these results with
      clinical research recently published by the authors. A systematic literature
      review based on the Preferred Reporting Items for Systematic Reviews and Meta
      Analyses: the PRISMA Statement was performed using comprehensive search criteria
      and communication with the authors. A meta-analysis considering the estimates of
      the univariate and bivariate models was performed. Specificity near 100% was
      common among the papers. The primary reason for accuracy differences was
      sensitivity. The meta-analysis, which was only possible for PCR samples of lesion
      fragments, revealed a sensitivity of 71% [95% confidence interval (CI) = 0.59;
      0.81] and a specificity of 93% (95% CI = 0.83; 0.98) in the bivariate model. The
      search for measures that could increase the sensitivity of PCR should be
      encouraged. The quality of the collected material and the optimisation of the
      amplification of genetic material should be prioritised. 

PMID- 25946239
TI  - The efficacy of 2-nitrovinylfuran derivatives against Leishmania in vitro and in
      vivo.
AB  - Despite recent advances in the treatment of some forms of leishmaniasis, the
      available drugs are still far from ideal due to inefficacy, parasite resistance,
      toxicity and cost. The wide-spectrum antimicrobial activity of 2-nitrovinylfuran
      compounds has been described, as has their activity against Trichomonas vaginalis
      and other protozoa. Thus, the aim of this study was to test the antileishmanial
      activities of six 2-nitrovinylfurans in vitro and in a murine model of
      leishmaniasis. Minimum parasiticide concentration (MPC) and 50% inhibitory
      concentration (IC50) values for these compounds against the promastigotes of
      Leishmania amazonensis, Leishmania infantum and Leishmania braziliensis were
      determined, as were the efficacies of two selected compounds in an experimental
      model of cutaneous leishmaniasis (CL) caused by L. amazonensis in BALB/c mice.
      All of the compounds were active against the promastigotes of the three
      Leishmania species tested. IC50 and MPC values were in the ranges of 0.8-4.7 uM
      and 1.7-32 uM, respectively. The compounds 2-bromo-5-(2-bromo-2-nitrovinyl)-furan
      (furvina) and 2-bromo-5-(2-methyl-2-nitrovinyl)-furan (UC245) also reduced lesion
      growth in vivo at a magnitude comparable to or higher than that achieved by
      amphotericin B treatment. The results demonstrate the potential of this class of
      compounds as antileishmanial agents and support the clinical testing of
      Dermofural(r) (a furvina-containing antifungal ointment) for the treatment of CL.

PMID- 25946240
TI  - Sandfly species diversity in association with human activities in the Kani tribe
      settlements of the Western Ghats, Thiruvananthapuram, Kerala, India.
AB  - Sandfly prevalence in the Kani tribe settlements of Western Ghats in India was
      investigated. A total of 1,279 sandflies comprising 17 species was obtained.
      Sandfly abundance showed a negative correlation (r = -0.97, p = 0.003) with
      increase in altitudinal ranges from 0-1,000 m. When sandfly samples were grouped
      according to landscape characteristics of the location, the estimated Shannon
      Weiner index (H) and species richness index (S) were high and species evenness
      index (J) was low in settlements located at 0-300 m altitudinal range. On the
      contrary, the values of H and J were high, while S was low at 301-600 m
      altitudinal range. With further increase in altitude, species diversity, S and J
      were low. Though the relative abundance of sandflies decreased with increase in
      altitude, the influence of altitudinal variation could not be attributed to
      determine sandfly diversity, since the number of sampling units were not uniform
      at all the altitudinal gradients due to nonavailability of suitable resting
      shelters. Sandfly species showed great aggregation at 0-300 m altitude interval,
      where not only the number of settlements were maximum (n = 19), but also the
      environmental conditions favoured sandfly abundance due to the concentration of
      tribal settlements, human dwellings and his activities.

PMID- 25946241
TI  - Role of cyclooxygenase-2 in Trypanosoma cruzi survival in the early stages of
      parasite host-cell interaction.
AB  - Chagas disease, caused by the intracellular protozoan Trypanosoma cruzi, is a
      serious health problem in Latin America. During this parasitic infection, the
      heart is one of the major organs affected. The pathogenesis of tissue
      remodelling, particularly regarding cardiomyocyte behaviour after parasite
      infection and the molecular mechanisms that occur immediately following parasite
      entry into host cells are not yet completely understood. When cells are infected
      with T. cruzi, they develop an inflammatory response, in which cyclooxygenase-2
      (COX-2) catalyses rate-limiting steps in the arachidonic acid pathway. However,
      how the parasite interaction modulates COX-2 activity is poorly understood. In
      this study, the H9c2 cell line was used as our model and we investigated cellular
      and biochemical aspects during the initial 48 h of parasitic infection.
      Oscillatory activity of COX-2 was observed, which correlated with the control of
      the pro-inflammatory environment in infected cells. Interestingly, subcellular
      trafficking was also verified, correlated with the control of Cox-2 mRNA or the
      activated COX-2 protein in cells, which is directly connected with the assemble
      of stress granules structures. Our collective findings suggest that in the very
      early stage of the T. cruzi-host cell interaction, the parasite is able to
      modulate the cellular metabolism in order to survives. 

PMID- 25946242
TI  - Factors associated with the occurrence of Triatoma sordida (Hemiptera:
      Reduviidae) in rural localities of Central-West Brazil.
AB  - This study estimates the factors of artificial environments (houses and
      peridomestic areas) associated with Triatoma sordida occurrence. Manual searches
      for triatomines were performed in 136 domiciliary units (DUs) in two rural
      localities of Central-West Brazil. For each DU, 32 structural, 23 biotic and 28
      management variables were obtained. Multiple logistic regression analysis was
      performed in order to identify statistically significant variables associated
      with occurrence of T. sordida in the study areas. A total of 1,057 specimens (99%
      in peridomiciles, mainly chicken coops) of T. sordida were collected from 63 DUs
      (infestation: 47%; density: ~8 specimens/DU; crowding: ~17 specimens/infested DU;
      colonisation: 81%). Only six (0.6%) out of 945 specimens examined were infected
      with Trypanosoma cruzi. The final adjusted logistic regression model indicated
      that the probability of T. sordida occurrence was higher in DU with wooden
      chicken coops, presence of > 30 animals in wooden corrals, presence of wood piles
      and presence of food storeroom. The results show the persistence of T. sordida in
      peridomestic habitats in rural localities of Central-West Brazil. However, the
      observed low intradomestic colonisation and minimal triatomine infection rates
      indicate that T. sordida has low potential to sustain high rates of T. cruzi
      transmission to residents of these localities. 

PMID- 25946244
TI  - Evaluation of parasitological and molecular techniques for the diagnosis and
      assessment of cure of schistosomiasis mansoni in a low transmission area.
AB  - This study evaluated parasitological and molecular techniques for the diagnosis
      and assessment of cure of schistosomiasis mansoni. A population-based study was
      performed in 201 inhabitants from a low transmission locality named Pedra Preta,
      municipality of Montes Claros, state of Minas Gerais, Brazil. Four stool samples
      were analysed using two techniques, the Kato-Katz(r) (KK) technique (18 slides)
      and the TF-Test(r), to establish the infection rate. The positivity rate of 18 KK
      slides of four stool samples was 28.9% (58/201) and the combined parasitological
      techniques (KK+TF-Test(r)) produced a 35.8% positivity rate (72/201).
      Furthermore, a polymerase chain reaction (PCR)-ELISA assay produced a positivity
      rate of 23.4% (47/201) using the first sample. All 72 patients with positive
      parasitological exams were treated with a single dose of Praziquantel(r) and
      these patients were followed-up 30, 90 and 180 days after treatment to establish
      the cure rate. Cure rates obtained by the analysis of 12 KK slides were 100%,
      100% and 98.4% at 30, 90 and 180 days after treatment, respectively. PCR-ELISA
      revealed cure rates of 98.5%, 95.5% and 96.5%, respectively. The diagnostic and
      assessment of cure for schistosomiasis may require an increased number of KK
      slides or a test with higher sensitivity, such as PCR-ELISA, in situations of
      very low parasite load, such as after therapeutic interventions. 

PMID- 25946243
TI  - Iron from haemoglobin and haemin modulates nucleotide hydrolysis in Trichomonas
      vaginalis.
AB  - Extracellular ATP may act as a danger signalling molecule, inducing inflammation
      and immune responses in infection sites. The ectonucleotidases NTPDase and ecto
      5'-nucleotidase are enzymes that modulate extracellular nucleotide levels; these
      enzymes have been previously characterised in Trichomonas vaginalis. Iron plays
      an important role in the complex trichomonal pathogenesis. Herein, the effects of
      iron on growth, nucleotide hydrolysis and NTPDase gene expression in T. vaginalis
      isolates from female and male patients were evaluated. Iron from different
      sources sustained T. vaginalis growth. Importantly, iron from haemoglobin (HB)
      and haemin (HM) enhanced NTPDase activity in isolates from female patients and
      conversely reduced the enzyme activity in isolates from male patients. Iron
      treatments could not alter the NTPDase transcript levels in T. vaginalis.
      Furthermore, our results reveal a distinct ATP, ADP and AMP hydrolysis profile
      between isolates from female and male patients influenced by iron from HB and HM.
      Our data indicate the participation of NTPDase and ecto-5'-nucleotidase in the
      establishment of trichomonas infection through ATP degradation and adenosine
      production influenced by iron. 

PMID- 25946246
TI  - Lactotransferrin gene functional polymorphisms do not influence susceptibility to
      human immunodeficiency virus-1 mother-to-child transmission in different ethnic
      groups.
AB  - Lactotransferrin, also known as lactoferrin, is an iron binding glycoprotein that
      displays antiviral activity against many different infectious agents, including
      human immunodeficiency virus (HIV)-1. Lactotransferrin is present in the breast
      milk and in the female genitourinary mucosa and it has been hypothesised as a
      possible candidate to prevent mother-to-child HIV-1 transmission. To verify if
      two functional polymorphisms, Thr29Ala and Arg47Lys, in the lactotransferrin
      encoding gene (LTF) could affect HIV-1 infection and vertical transmission, a
      preliminary association study was performed in 238 HIV-1 positive and 99 HIV-1
      negative children from Brazil, Italy, Africa and India. No statistically
      significant association for the Thr29Ala and Arg47Lys LTF polymorphisms and HIV-1
      susceptibility in the studied populations was found. Additionally LTF
      polymorphisms frequencies were compared between the four different ethnic groups.

PMID- 25946245
TI  - The prevalence of norovirus, astrovirus and adenovirus infections among
      hospitalised children with acute gastroenteritis in Porto Velho, state of
      Rondonia, western Brazilian Amazon.
AB  - Although viruses are well-established causes of acute gastroenteritis, few data
      on the circulation of these pathogens in Porto Velho, state of Rondonia, Brazil,
      are available. Thus, faecal samples from hospitalised diarrhoeic children, under
      six years of age, were collected and tested for the presence of norovirus (NoV),
      adenovirus (AdV) and astrovirus (AstV) from February 2010-February 2012.
      Specimens were screened by reverse-transcription polymerase chain reaction and
      viruses were found in 10.7% (63/591) of the cases. NoV, AdV and AstV were
      detected in 7.8%, 2% and 0.8% of the samples, respectively. NoV infection was
      observed at all ages and was most prevalent in zero-18-month-old children (84.7%;
      p = 0.002). A higher incidence of NoV was detected from February-April 2010, when
      it was found in 52.2% of the cases. Co-infections involving these viruses,
      rotavirus and enteropathogenic bacteria were detected in 44.4% (28/63) of the
      children with viral diarrhoea. Nosocomial infections were demonstrated in 28.6%
      (18/63) of the cases in which viruses were detected. The present paper reports,
      for the first time, the circulation of NoV and AstV among the paediatric
      population of Porto Velho and it contributes to our understanding of the roles of
      these pathogens in gastrointestinal infections. 

PMID- 25946247
TI  - A public health risk assessment for yellow fever vaccination: a model exemplified
      by an outbreak in the state of Sao Paulo, Brazil.
AB  - We propose a method to analyse the 2009 outbreak in the region of Botucatu in the
      state of Sao Paulo (SP), Brazil, when 28 yellow fever (YF) cases were confirmed,
      including 11 deaths. At the time of the outbreak, the Secretary of Health of the
      State of Sao Paulo vaccinated one million people, causing the death of five
      individuals, an unprecedented number of YF vaccine-induced fatalities. We apply a
      mathematical model described previously to optimise the proportion of people who
      should be vaccinated to minimise the total number of deaths. The model was used
      to calculate the optimum proportion that should be vaccinated in the remaining,
      vaccine-free regions of SP, considering the risk of vaccine-induced fatalities
      and the risk of YF outbreaks in these regions. 

PMID- 25946248
TI  - Clinical and epidemiological profiles of individuals with drug-resistant
      tuberculosis.
AB  - Drug-resistant tuberculosis (TB) is a growing global threat. Approximately
      450,000 people developed multidrug-resistant TB worldwide in 2012 and an
      estimated 170,000 people died from the disease. This paper describes the
      sociodemographic, clinical-epidemiological and bacteriological aspects of TB and
      correlates these features with the distribution of anti-TB drug resistance.
      Mycobacterium tuberculosis (MT) cultures and drug susceptibility testing were
      performed according to the BACTEC MGIT 960 method. The results demonstrated that
      MT strains from individuals who received treatment for TB and people who were
      infected with human immunodeficiency virus were more resistant to TB drugs
      compared to other individuals (p < 0.05). Approximately half of the individuals
      received supervised treatment, but most drug-resistant cases were positive for
      pulmonary TB and exhibited positive acid-fast bacilli smears, which are
      complicating factors for TB control programs. Primary healthcare is the ideal
      level for early disease detection, but tertiary healthcare is the most common
      entry point for patients into the system. These factors require special attention
      from healthcare managers and professionals to effectively control and monitor the
      spread of TB drug-resistant cases. 

PMID- 25946249
TI  - Biofilm production by multiresistant Corynebacterium striatum associated with
      nosocomial outbreak.
AB  - Corynebacterium striatum is a potentially pathogenic microorganism that causes
      nosocomial outbreaks. However, little is known about its virulence factors that
      may contribute to healthcare-associated infections (HAIs). We investigated the
      biofilm production on abiotic surfaces of multidrug-resistant (MDR) and multidrug
      susceptible (MDS) strains of C. striatum of pulsed-field gel electrophoresis
      types I-MDR, II-MDR, III-MDS and IV-MDS isolated during a nosocomial outbreak in
      Rio de Janeiro, Brazil. The results showed that C. striatum was able to adhere to
      hydrophilic and hydrophobic abiotic surfaces. The C. striatum 1987/I-MDR strain,
      predominantly isolated from patients undergoing endotracheal intubation
      procedures, showed the greatest ability to adhere to all surfaces. C. striatum
      bound fibrinogen to its surface, which contributed to biofilm formation. Scanning
      electron microscopy showed the production of mature biofilms on polyurethane
      catheters by all pulsotypes. In conclusion, biofilm production may contribute to
      the establishment of HAIs caused by C. striatum. 

PMID- 25946250
TI  - Widespread distribution of CTX-M and plasmid-mediated AmpC beta-lactamases in
      Escherichia coli from Brazilian chicken meat.
AB  - The dissemination of plasmid-mediated antimicrobial resistance genes may pose a
      substantial public health risk. In the present work, the occurrences of blaCTX-M
      and plasmid-mediated ampC and qnr genes were investigated in Escherichia coli
      from 16 chicken carcasses produced by four commercial brands in Brazil. Of the
      brands tested, three were exporters, including one of organic chicken. Our study
      assessed 136 E. coli isolates that were grouped into 77 distinct biotypes defined
      by their origin, resistance profiling, the presence of beta-lactamase and plasmid
      mediated quinolone resistance genes and enterobacterial repetitive intergenic
      consensus-polimerase chain reaction typing. The blaCTX-M-15, blaCTX-M-2 and
      blaCTX-M-8 genes were detected in one, 17 and eight different biotypes,
      respectively (45 isolates). Twenty-one biotypes (46 isolates) harboured blaCMY-2.
      Additionally, blaCMY-2 was identified in isolates that also carried either blaCTX
      M-2 or blaCTX-M-8. The qnrB and/or qnrS genes occurred in isolates carrying each
      of the four types of beta-lactamase determinants detected and also in oxyimino
      cephalosporin-susceptible strains. Plasmid-mediated extended-spectrum beta
      lactamase (ESBL) and AmpC determinants were identified in carcasses from the four
      brands tested. Notably, this is the first description of blaCTX-M-15 genes in
      meat or food-producing animals from South America. The blaCTX-M-8, blaCTX-M-15
      and blaCMY-2 genes were transferable in conjugation experiments. The findings of
      the present study indicate that plasmid-mediated ESBL and AmpC-encoding genes are
      widely distributed in Brazilian chicken meat. 

PMID- 25946252
TI  - Waiting for chikungunya fever in Argentina: spatio-temporal risk maps.
AB  - Chikungunya virus (CHIKV) transmission has been detected in America in 2013 and
      recently reached south up to Bolivia, Brazil and Paraguay, bordering countries of
      Argentina. The presence of the mosquito Aedes aegypti in half of the country
      together with the regional context drove us to make a rapid assessment of
      transmission risk. Temperature thresholds for vector breeding and for virus
      transmission, together with adult activity from the literature, were mapped on a
      monthly basis to estimate risk. Transmission of chikungunya by Ae. aegypti in the
      world was seen at monthly mean temperatures from 21-34oC, with the majority
      occurring between 26-28oC. In Argentina temperatures above 21oC are observed
      since September in the northeast, expanding south until January and retreating
      back to the northeast in April. The maximum area under risk encompasses more than
      half the country and around 32 million inhabitants. Vector adult activity was
      registered where monthly means temperatures exceeded 13oC, in the northeast all
      over the year and in the northern half from September-May. The models herein
      proposed show that conditions for transmission are already present. Considering
      the regional context and the historic inability to control dengue in the region,
      chikungunya fever illness seems unavoidable. 

PMID- 25946251
TI  - Structure-based drug design studies of the interactions of ent-kaurane diterpenes
      derived from Wedelia paludosa with the Plasmodium falciparum sarco/endoplasmic
      reticulum Ca2+-ATPase PfATP6.
AB  - Malaria is responsible for more deaths around the world than any other parasitic
      disease. Due to the emergence of strains that are resistant to the current
      chemotherapeutic antimalarial arsenal, the search for new antimalarial drugs
      remains urgent though hampered by a lack of knowledge regarding the molecular
      mechanisms of artemisinin resistance. Semisynthetic compounds derived from
      diterpenes from the medicinal plant Wedelia paludosa were tested in silico
      against the Plasmodium falciparum Ca2+-ATPase, PfATP6. This protein was
      constructed by comparative modelling using the three-dimensional structure of a
      homologous protein, 1IWO, as a scaffold. Compound 21 showed the best docking
      scores, indicating a better interaction with PfATP6 than that of thapsigargin,
      the natural inhibitor. Inhibition of PfATP6 by diterpene compounds could promote
      a change in calcium homeostasis, leading to parasite death. These data suggest
      PfATP6 as a potential target for the antimalarial ent-kaurane diterpenes. 

PMID- 25946253
TI  - T-helper 17-related cytokines and IgE antibodies during hepatitis A virus
      infection in children.
AB  - We determined the serum IgE levels and T-helper (Th)17-related cytokines during
      distinct hepatitis A virus (HAV)-induced clinical courses in children. A
      significantly higher concentration of macrophage inflammatory protein 3alpha,
      interleukin (IL)-17E and IL-17F in HAV-infected children with intermediate liver
      injury compared with those with minor liver damage was found. A reduction in the
      IgE levels in those patients who showed the highest levels of IL-17F in the group
      of intermediate liver injury was found. The data suggested that the Th17-related
      profile is associated with the severity of HAV infection and might play a role on
      the modulation achieved by HAV during allergies.

PMID- 25946254
TI  - Spontaneous hepatitis C viral clearance and hepatitis C chronic infection are
      associated with distinct cytokine profiles in Mexican patients.
AB  - The mechanisms related to the spontaneous clearance of hepatitis C virus (HCV)
      have been primarily studied in regions where the infection is endemic. Results of
      prior studies have been extrapolated to populations with low endemicity, such as
      Mexico. Herein, we determined the cytokine profiles in serum samples from Mexican
      patients who spontaneously cleared HCV and patients chronically infected with HCV
      genotype 1a. Chronic HCV-infected patients displayed increased interleukin (IL)-8
      and regulated upon activation, normal T-cell expressed and secreted (CCL-5)
      secretion, whereas patients who spontaneously cleared HCV showed augmented levels
      of IL-1 alpha, tumour necrosis factor-alpha, transforming growth factor-beta,
      monocyte chemoattractant protein-2 (CCL-8), IL-13 and IL-15. Our study suggests
      that cytokine profiles may predict disease outcome during HCV infection.

PMID- 25946255
TI  - Molecular diagnosis of strongyloidiasis in tropical areas: a comparison of
      conventional and real-time polymerase chain reaction with parasitological
      methods.
AB  - This study aimed to evaluate the use of conventional polymerase chain reaction
      (cPCR) and real-time quantitative PCR (qPCR) in the diagnosis of human
      strongyloidiasis from stool samples in tropical areas. Stool samples were
      collected from individuals and were determined to be positive for Strongyloides
      stercoralis (group I), negative for S. stercoralis (group II) and positive for
      other enteroparasite species (group III). DNA specific to S. stercoralis was
      found in 76.7% of group I samples by cPCR and in 90% of group I samples by qPCR.
      The results show that molecular methods can be used as alternative tools for
      detecting S. stercoralis in human stool samples in tropical areas. 

PMID- 25946256
TI  - Glioblastoma multiforme in a child with tuberous sclerosis complex.
AB  - Tuberous Sclerosis Complex (TSC) is characterized by the presence of benign
      tumors in the brain, kidneys, heart, eyes, lungs, and skin. The typical brain
      lesions are cortical tubers, subependimal nodules and subependymal giant-cell
      astrocytomas. The occurrence of malignant astrocytomas such as glioblastoma is
      rare. We report on a child with a clinical diagnosis of TSC and a rapidly
      evolving glioblastoma multiforme. Genetic analysis identified a de novo mutation
      in TSC2. Molecular characterization of the tumor was performed and discussed, as
      well as a review of the literature where cases of TSC and glioblastoma multiforme
      are described. Although the co-occurrence of TSC and glioblastoma multiforme
      seems to be rare, this possible association should be kept in mind, and proper
      clinical and radiological follow up should be recommended in these patients.

PMID- 25946258
TI  - Nanoparticle characterization by means of scanning free grazing emission X-ray
      fluorescence.
AB  - Nanoparticles are considered for applications in domains as various as medical
      and pharmaceutical sciences, opto- and microelectronics, catalysis,
      photovoltaics, spintronics or nano- and biotechnology. The applications realized
      with nanocrystals depend strongly on the physical dimensions (shape and size) and
      elemental constitution. We demonstrate here that grazing emission X-ray
      fluorescence (GEXRF) is an element sensitive technique that presents the
      potential for a reliable and accurate determination of the morphology of
      nanoparticles deposited on a flat substrate (ready-to-use devices). Thanks to the
      scanning-free approach of the used GEXRF setup, the composition, shape and
      average size of nanoparticles are determined in short time intervals, minimizing
      the exposure to radiation. The (scanning-free) GEXRF technique allows for in situ
      investigations of the nanoparticulate systems thanks to the penetration
      properties of both the probe X-ray beam and the emitted X-ray fluorescence
      signal. 

PMID- 25946259
TI  - Planning Fireworks Trajectories for Steerable Medical Needles to Reduce Patient
      Trauma.
AB  - Accurate insertion of needles to targets in 3D anatomy is required for numerous
      medical procedures. To reduce patient trauma, a "fireworks" needle insertion
      approach can be used in which multiple needles are inserted from a single small
      region on the patient's skin to multiple targets in the tissue. In this paper, we
      explore motion planning for "fireworks" needle insertion in 3D environments by
      developing an algorithm based on Rapidly-exploring Random Trees (RRTs). Given a
      set of targets, we propose an algorithm to quickly explore the configuration
      space by building a forest of RRTs and to find feasible plans for multiple
      steerable needles from a single entry region. We present two path selection
      algorithms with different optimality considerations to optimize the final plan
      among all feasible outputs. Finally, we demonstrate the performance of the
      proposed algorithm with a simulation based on a prostate cancer treatment
      environment.

PMID- 25946257
TI  - Historical Invasion Records Can Be Misleading: Genetic Evidence for Multiple
      Introductions of Invasive Raccoons (Procyon lotor) in Germany.
AB  - Biological invasions provide excellent study systems to understand evolutionary,
      genetic and ecological processes during range expansions. There is strong
      evidence for positive effects of high propagule pressure and the associated
      higher genetic diversity on invasion success, but some species have become
      invasive despite small founder numbers. The raccoon (Procyon lotor) is often
      considered as a typical example for such a successful invasion resulting from a
      small number of founders. The species' largest non-native population in Germany
      is commonly assumed to stem from a small number of founders and two separate
      founding events in the 1930s and 1940s. In the present study we analyzed 407
      raccoons at 20 microsatellite loci sampled from the invasive range in Western
      Europe to test if these assumptions are correct. Contrary to the expectations,
      different genetic clustering methods detected evidence for at least four
      independent introduction events that gave rise to genetically differentiated
      subpopulations. Further smaller clusters were either artifacts or resulted from
      founder events at the range margin and recent release of captive individuals. We
      also found genetic evidence for on-going introductions of individuals.
      Furthermore a novel randomization process was used to determine the potential
      range of founder population size that would suffice to capture all the alleles
      present in a cluster. Our results falsify the assumption that this species has
      become widespread and abundant despite being genetically depauperate and show
      that historical records of species introductions may be misleading. 

PMID- 25946260
TI  - Sample holder for axial rotation of specimens in 3D microscopy.
AB  - In common light microscopy, observation of samples is only possible from one
      perspective. However, especially for larger three-dimensional specimens
      observation from different views is desirable. Therefore, we are presenting a
      sample holder permitting rotation of the specimen around an axis perpendicular to
      the light path of the microscope. Thus, images can be put into a defined
      multidimensional context, enabling reliable three-dimensional reconstructions.
      The device can be easily adapted to a great variety of common light microscopes
      and is suitable for various applications in science, education and industry,
      where the observation of three-dimensional specimens is essential. Fluorescence z
      projection images of copepods and ixodidae ticks at different rotation angles
      obtained by confocal laser scanning microscopy and light sheet fluorescence
      microscopy are reported as representative results. 

PMID- 25946261
TI  - On risk factors for pediatric delirium at noon.

PMID- 25946262
TI  - Functional status after pediatric critical care: is it the disease, the cure, or
      both?

PMID- 25946263
TI  - Taking one for the team.

PMID- 25946264
TI  - A new name for respiratory distress associated with transfusion.

PMID- 25946265
TI  - That went well, or did it? Fighting rosy recall in the documentation of in
      hospital cardiac arrest.

PMID- 25946266
TI  - Therapeutic plasma exchange as a strategy to reverse multiple organ dysfunction
      syndrome in patients receiving extracorporeal life support.

PMID- 25946267
TI  - Are we correctly diagnosing adrenal insufficiency or are we just spitting into
      the wind?

PMID- 25946268
TI  - Advancing Our Understanding of the Psychological Impact of PICU Hospitalization:
      Is It Time to Pause and Reflect?

PMID- 25946269
TI  - The right therapy at the right time in the right patient.

PMID- 25946270
TI  - The authors reply.

PMID- 25946271
TI  - Sepsis Is SEPSIS! It's High Time to Globalize Pediatric Sepsis.

PMID- 25946272
TI  - The authors reply.

PMID- 25946273
TI  - The authors reply.

PMID- 25946274
TI  - The authors reply.

PMID- 25946275
TI  - Invasive measurement of global end-diastolic volume: is it possible to add any
      data besides clinical parameters?

PMID- 25946276
TI  - The authors reply.

PMID- 25946277
TI  - Integrated ambulatory specialist care--Germany's new health care sector.

PMID- 25946278
TI  - Lessons in medicine, mortality, and reflexive verbs.

PMID- 25946279
TI  - Between-hospital variation in treatment and outcomes in extremely preterm
      infants.
AB  - BACKGROUND: Between-hospital variation in outcomes among extremely preterm
      infants is largely unexplained and may reflect differences in hospital practices
      regarding the initiation of active lifesaving treatment as compared with comfort
      care after birth. METHODS: We studied infants born between April 2006 and March
      2011 at 24 hospitals included in the Eunice Kennedy Shriver National Institute of
      Child Health and Human Development Neonatal Research Network. Data were collected
      for 4987 infants born before 27 weeks of gestation without congenital anomalies.
      Active treatment was defined as any potentially lifesaving intervention
      administered after birth. Survival and neurodevelopmental impairment at 18 to 22
      months of corrected age were assessed in 4704 children (94.3%). RESULTS: Overall
      rates of active treatment ranged from 22.1% (interquartile range [IQR], 7.7 to
      100) among infants born at 22 weeks of gestation to 99.8% (IQR, 100 to 100) among
      those born at 26 weeks of gestation. Overall rates of survival and survival
      without severe impairment ranged from 5.1% (IQR, 0 to 10.6) and 3.4% (IQR, 0 to
      6.9), respectively, among children born at 22 weeks of gestation to 81.4% (IQR,
      78.2 to 84.0) and 75.6% (IQR, 69.5 to 80.0), respectively, among those born at 26
      weeks of gestation. Hospital rates of active treatment accounted for 78% and 75%
      of the between-hospital variation in survival and survival without severe
      impairment, respectively, among children born at 22 or 23 weeks of gestation, and
      accounted for 22% and 16%, respectively, among those born at 24 weeks of
      gestation, but the rates did not account for any of the variation in outcomes
      among those born at 25 or 26 weeks of gestation. CONCLUSIONS: Differences in
      hospital practices regarding the initiation of active treatment in infants born
      at 22, 23, or 24 weeks of gestation explain some of the between-hospital
      variation in survival and survival without impairment among such patients.
      (Funded by the National Institutes of Health.).

PMID- 25946280
TI  - Approaches to catheter ablation for persistent atrial fibrillation.
AB  - BACKGROUND: Catheter ablation is less successful for persistent atrial
      fibrillation than for paroxysmal atrial fibrillation. Guidelines suggest that
      adjuvant substrate modification in addition to pulmonary-vein isolation is
      required in persistent atrial fibrillation. METHODS: We randomly assigned 589
      patients with persistent atrial fibrillation in a 1:4:4 ratio to ablation with
      pulmonary-vein isolation alone (67 patients), pulmonary-vein isolation plus
      ablation of electrograms showing complex fractionated activity (263 patients), or
      pulmonary-vein isolation plus additional linear ablation across the left atrial
      roof and mitral valve isthmus (259 patients). The duration of follow-up was 18
      months. The primary end point was freedom from any documented recurrence of
      atrial fibrillation lasting longer than 30 seconds after a single ablation
      procedure. RESULTS: Procedure time was significantly shorter for pulmonary-vein
      isolation alone than for the other two procedures (P<0.001). After 18 months, 59%
      of patients assigned to pulmonary-vein isolation alone were free from recurrent
      atrial fibrillation, as compared with 49% of patients assigned to pulmonary-vein
      isolation plus complex electrogram ablation and 46% of patients assigned to
      pulmonary-vein isolation plus linear ablation (P=0.15). There were also no
      significant differences among the three groups for the secondary end points,
      including freedom from atrial fibrillation after two ablation procedures and
      freedom from any atrial arrhythmia. Complications included tamponade (three
      patients), stroke or transient ischemic attack (three patients), and
      atrioesophageal fistula (one patient). CONCLUSIONS: Among patients with
      persistent atrial fibrillation, we found no reduction in the rate of recurrent
      atrial fibrillation when either linear ablation or ablation of complex
      fractionated electrograms was performed in addition to pulmonary-vein isolation.
      (Funded by St. Jude Medical; ClinicalTrials.gov number, NCT01203748.).

PMID- 25946282
TI  - Iron-deficiency anemia.

PMID- 25946281
TI  - Changes in Medicare costs with the growth of hospice care in nursing homes.
AB  - BACKGROUND: Nursing home residents' use of hospice has substantially increased.
      Whether this increase in hospice use reduces end-of-life expenditures is unknown.
      METHODS: The expansion of hospice between 2004 and 2009 created a natural
      experiment, allowing us to conduct a difference-in-differences matched analysis
      to examine changes in Medicare expenditures in the last year of life that were
      associated with this expansion. We also assessed intensive care unit (ICU) use in
      the last 30 days of life and, for patients with advanced dementia, feeding-tube
      use and hospital transfers within the last 90 days of life. We compared a subset
      of hospice users from 2009, whose use of hospice was attributed to hospice
      expansion, with a matched subset of non-hospice users from 2004, who were
      considered likely to have used hospice had they died in 2009. RESULTS: Of 786,328
      nursing home decedents, 27.6% in 2004 and 39.8% in 2009 elected to use hospice.
      The 2004 and 2009 matched hospice and nonhospice cohorts were similar (mean age,
      85 years; 35% male; 25% with cancer). The increase in hospice use was associated
      with significant decreases in the rates of hospital transfers (2.4 percentage
      point reduction), feeding-tube use (1.2 percentage-point reduction), and ICU use
      (7.1 percentage-point reduction). The mean length of stay in hospice increased
      from 72.1 days in 2004 to 92.6 days in 2009. Between 2004 and 2009, the expansion
      of hospice was associated with a mean net increase in Medicare expenditures of
      $6,761 (95% confidence interval, 6,335 to 7,186), reflecting greater additional
      spending on hospice care ($10,191) than reduced spending on hospital and other
      care ($3,430). CONCLUSIONS: The growth in hospice care for nursing home residents
      was associated with less aggressive care near death but at an overall increase in
      Medicare expenditures. (Funded by the Centers for Medicare and Medicaid Services
      and the National Institute on Aging.).

PMID- 25946283
TI  - Images in clinical medicine. Conjunctival melanoma.

PMID- 25946284
TI  - Clinical problem-solving. Sick as a dog.

PMID- 25946285
TI  - Revisiting the commercial-academic interface.

PMID- 25946286
TI  - The elephant in the delivery room.

PMID- 25946287
TI  - Investing in better care for patients dying in nursing homes.

PMID- 25946288
TI  - Conflicts of interest: part 1: Reconnecting the dots--reinterpreting industry
      physician relations.

PMID- 25946289
TI  - Effect of mutation order on myeloproliferative neoplasms.

PMID- 25946290
TI  - Effect of mutation order on myeloproliferative neoplasms.

PMID- 25946291
TI  - Icatibant in ACE-inhibitor-induced angioedema.

PMID- 25946292
TI  - Icatibant in ACE-inhibitor-induced angioedema.

PMID- 25946293
TI  - Icatibant in ACE-inhibitor-induced angioedema.

PMID- 25946294
TI  - Icatibant in ACE-inhibitor-induced angioedema.

PMID- 25946295
TI  - Lenvatinib in radioiodine-refractory thyroid cancer.

PMID- 25946296
TI  - Lenvatinib in radioiodine-refractory thyroid cancer.

PMID- 25946297
TI  - HDL cholesterol efflux capacity and cardiovascular events.

PMID- 25946298
TI  - HDL cholesterol efflux capacity and cardiovascular events.

PMID- 25946299
TI  - HDL cholesterol efflux capacity and cardiovascular events.

PMID- 25946300
TI  - HDL cholesterol efflux capacity and cardiovascular events.

PMID- 25946301
TI  - HDL cholesterol efflux capacity and cardiovascular events.

PMID- 25946302
TI  - A longitudinal study of bullying of sexual-minority youth.

PMID- 25946303
TI  - Medicare's step back from global payments--unbundling postoperative care.

PMID- 25946304
TI  - Images in clinical medicine. Trapped lung.

PMID- 25946305
TI  - Increased Athletic Performance in Lighter Basketball Shoes: Shoe or Psychology
      Effect?
AB  - PURPOSE: To determine the effect of shoe mass on performance in basketball
      specific movements and how this affects changes if an athlete is aware or not of
      the shoe's mass relative to other shoes. METHODS: In an experimental design, 22
      male participants were assigned to 2 groups. In the "aware" group, differences in
      the mass of the shoes were disclosed, while participants in the other group were
      blinded to the mass of shoes. For both groups lateral shuffle-cut and vertical
      jump performances were quantified in 3 different basketball-shoe conditions
      (light, 352 +/- 18.4 g; medium, 510 +/- 17 g; heavy, 637 +/- 17.7 g). A mixed
      ANOVA compared mean shuffle-cut and vertical-jump performances across shoes and
      groups. For blinded participants, perceived shoe-weight ratings were collected
      and compared across shoe conditions using a Friedman 2-way ANOVA. RESULTS: In the
      aware group, performance in the light shoes was significantly increased by 2%
      (vertical jump 2%, P < .001; shuffle cut 2.1%, P < .001) compared with the heavy
      shoes. In the blind group, participants were unable to perceive the shoe-weight
      variation between conditions, and there were no significant differences in
      vertical-jump and shuffle-cut performance across shoes. CONCLUSIONS: Differences
      in performance of the aware participants were most likely due to psychological
      effects such as positive and negative expectancies toward the light and heavy
      shoes, respectively. These results underline the importance for coaches and shoe
      manufacturers to communicate the performance-enhancing benefits of products or
      other interventions to athletes to optimize their performance outcome.

PMID- 25946306
TI  - Reading a suspenseful literary text activates brain areas related to social
      cognition and predictive inference.
AB  - Stories can elicit powerful emotions. A key emotional response to narrative plots
      (e.g., novels, movies, etc.) is suspense. Suspense appears to build on basic
      aspects of human cognition such as processes of expectation, anticipation, and
      prediction. However, the neural processes underlying emotional experiences of
      suspense have not been previously investigated. We acquired functional magnetic
      resonance imaging (fMRI) data while participants read a suspenseful literary text
      (E.T.A. Hoffmann's "The Sandman") subdivided into short text passages. Individual
      ratings of experienced suspense obtained after each text passage were found to be
      related to activation in the medial frontal cortex, bilateral frontal regions
      (along the inferior frontal sulcus), lateral premotor cortex, as well as
      posterior temporal and temporo-parietal areas. The results indicate that the
      emotional experience of suspense depends on brain areas associated with social
      cognition and predictive inference. 

PMID- 25946308
TI  - Letter: a case supporting the use of rescue infliximab therapy for fulminant
      ulcerative colitis in pregnancy.

PMID- 25946307
TI  - High temporal resolution dynamic MRI and arterial input function for assessment
      of GFR in pediatric subjects.
AB  - PURPOSE: To introduce a respiratory-gated high-spatiotemporal-resolution dynamic
      contrast-enhanced MRI technique and a high-temporal-resolution aortic input
      function (HTR-AIF) estimation method for glomerular filtration rate (GFR)
      assessment in children. METHODS: A high-spatiotemporal-resolution DCE-MRI method
      with view-shared reconstruction was modified to incorporate respiratory gating,
      and an AIF estimation method that uses a fraction of the k-space data from each
      respiratory period was developed (HTR-AIF). The method was validated using
      realistic digital phantom simulations and demonstrated on clinical subjects. The
      GFR estimates using HTR-AIF were compared with estimates obtained by using an AIF
      derived directly from the view-shared images. RESULTS: Digital phantom
      simulations showed that using the HTR-AIF technique gives more accurate AIF
      estimates (RMSE = 0.0932) compared with the existing estimation method (RMSE =
      0.2059) that used view-sharing (VS). For simulated GFR > 27 mL/min, GFR
      estimation error was between 32% and 17% using view-shared AIF, whereas
      estimation error was less than 10% using HTR-AIF. In all clinical subjects, the
      HTR-AIF method resulted in higher GFR estimations than the view-shared method.
      CONCLUSION: The HTR-AIF method improves the accuracy of both the AIF and GFR
      estimates derived from the respiratory-gated acquisitions, and makes GFR
      estimation feasible in free-breathing pediatric subjects.

PMID- 25946310
TI  - A Mechanically Strong, Highly Stable, Thermoplastic, and Self-Healable
      Supramolecular Polymer Hydrogel.
AB  - Polymerization of glycinamide-conjugated monomer alone in concentrated aqueous
      solution enables facile formation of a mechanically strong and a highly stable
      supramolecular polymer (SP) hydrogel because of the cooperatively hydrogen-bonded
      crosslinking and strengthening effect from dual amide motifs. This SP hydrogel
      exhibits thermoplastic processability, injectability, and self-reparability
      because of the dynamic destruction and reconstruction of hydrogen bonds in
      response to temperature change. 

PMID- 25946311
TI  - EVALUATION OF THE ROLE OF NURSE PRACTITIONERS IN MASTERPLAN.
AB  - BACKGROUND: Preserving kidney function and prevention of cardiovascular disease
      can only be achieved if patients are supported in self-managing their disease
      aimed at developing coping strategies. OBJECTIVES: In MASTERPLAN, a clinical
      trial from 2005 -2010, patients with chronic kidney disease were randomised to
      receive nurse practitioner (NP) support or physician care alone. We evaluated the
      role of NP and patients in achieving lifestyle treatment goals. However the
      evaluation of lifestyle interventions resulted in disappointing findings. DESIGN:
      We conducted a mixed method study to explain the previous quantitative results in
      order to achieve a more complete description of the practice of reaching
      lifestyle goals. PARTICIPANTS: Ten NPs in nine participating hospitals of the
      MASTERPLAN study were interviewed and identified a hierarchy on what treatment
      goals received the most attention during MASTERPLAN, at baseline and after four
      years. RESULTS: A shift of attention in study goals occured for various reasons
      e.g. progression of disease, too many goals, non-motivated patients, changed
      relationship between NP and patient. Different strategies were used to influence
      lifestyle change with varying degrees of success. CONCLUSION: Lifestyle change is
      difficult to maintain during five years follow up. Besides a shift of attention
      in study goals, the relationship with the patient also changed over time.

PMID- 25946312
TI  - Asymmetric Biocatalytic Amination of Ketones at the Expense of NH3 and Molecular
      Hydrogen.
AB  - A biocatalytic system is presented for the stereoselective amination of ketones
      at the expense of NH3 and molecular hydrogen. By using a NAD(+)-reducing
      hydrogenase, an alanine dehydrogenase, and a suitable omega-transaminase, the R-
      as well as the S-enantiomer of various amines could be prepared with up to >99%
      ee and 98% conversion. 

PMID- 25946313
TI  - Efficient near-infrared downconversion and energy transfer mechanism of
      ce(3+)/yb(3+) codoped calcium scandate phosphor.
AB  - An efficient near-infrared (NIR) downconversion has been demonstrated in CaSc2O4:
      Ce(3+)/Yb(3+) phosphor. Doping concentration optimized CaSc2O4: 1%Ce(3+)/5%Yb(3+)
      shows stronger NIR emission than doping concentration also optimized typical YAG:
      1%Ce(3+)/5%Yb(3+) under 470 nm excitation. The NIR emission from 900 to 1100 nm
      is enhanced by a factor of 2.4. In addition, the main emission peak of Yb(3+) in
      the CaSc2O4 around 976 nm matches better with the optimal spectral response of
      the c-Si solar cell. The visible and NIR spectra and the decay curves of Ce(3+):
      5d -> 4f emission were used to demonstrate the energy transfer from Ce(3+) ions
      to Yb(3+) ions. The downconversion phenomenon has been observed under the direct
      excitation of Ce(3+) ions. On analyzing the dependence of energy transfer rate on
      Yb(3+) ion concentration, we reveal that the energy transfer (ET) from Ce(3+)
      ions to Yb(3+) ions in CaSc2O4 occurs mainly by the single-step ET process.
      Considering that the luminescence efficiency of CaSc2O4: Ce(3+) is comparable to
      that of commercial phosphor YAG: Ce(3+), the estimated maximum energy transfer
      efficiency reaches 58% in the CaSc2O4: 1%Ce(3+)/15%Yb(3+) sample, indicating that
      CaSc2O4: Ce(3+)/Yb(3+) sample has the potential in improving the conversion
      efficiency of c-Si solar cells. 

PMID- 25946314
TI  - Rapid and Localized Mechanical Stimulation and Adhesion Assay: TRPM7 Involvement
      in Calcium Signaling and Cell Adhesion.
AB  - A cell mechanical stimulation equipment, based on cell substrate deformation, and
      a more sensitive method for measuring adhesion of cells were developed. A probe,
      precisely positioned close to the cell, was capable of a vertical localized
      mechanical stimulation with a temporal frequency of 207 Hz, and strain magnitude
      of 50%. This setup was characterized and used to probe the response of Human
      Umbilical Endothelial Vein Cells (HUVECs) in terms of calcium signaling. The
      intracellular calcium ion concentration was measured by the genetically encoded
      Cameleon biosensor, with the Transient Receptor Potential cation channel,
      subfamily M, member 7 (TRPM7) expression inhibited. As TRPM7 expression also
      regulates adhesion, a relatively simple method for measuring adhesion of cells
      was also developed, tested and used to study the effect of adhesion alone. Three
      adhesion conditions of HUVECs on polyacrylamide gel dishes were compared. In the
      first condition, the substrate is fully treated with Sulfo-SANPAH crosslinking
      and fibronectin. The other two conditions had increasingly reduced adhesion:
      partially treated (only coated with fibronectin, with no use of Sulfo-SANPAH, at
      5% of the normal amount) and non-treated polyacrylamide gels. The cells showed
      adhesion and calcium response to the mechanical stimulation correlated to the
      degree of gel treatment: highest for fully treated gels and lowest for non
      treated ones. TRPM7 inhibition by siRNA on HUVECs caused an increase in adhesion
      relative to control (no siRNA treatment) and non-targeting siRNA, but a decrease
      to 80% of calcium response relative to non-targeting siRNA which confirms the
      important role of TRPM7 in mechanotransduction despite the increase in adhesion. 

PMID- 25946315
TI  - Forced unfolding of single-chain polymeric nanoparticles.
AB  - Atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) is
      applied to single-chain polymeric nanoparticles (SCPNs) to acquire information
      about the internal folding structure of SCPNs and inherent kinetic parameters of
      supramolecular self-assembling motifs embedded into the SCPNs. The SCPNs used
      here are polyacrylate-based polymers carrying 2-ureido-4-[1H]-pyrimidinone (UPy)
      or benzene-1,3,5-tricarboxamide (BTA) pendants that induce an intramolecular
      chain collapse into nanoparticles consisting of one polymer chain only via
      internal supramolecular cross-linking. The SCPN is stretched by an AFM cantilever
      to unfold mechanically, which allows measuring of force-extension profiles of the
      SCPNs. Consecutive peaks observed in the force profiles are attributed to rupture
      events of self-assembled UPy/BTA units in the SCPNs. The force profiles have been
      analyzed statistically for a series of polymers with different UPy/BTA
      incorporation densities. The results provide insights into the internal
      conformation of SCPNs, where the folding structure can be changed with the
      incorporation density of UPy/BTA. In addition, dynamic loading rate analysis
      allows the determination of kinetic parameters of BTA self-assembly, which has
      not been accessible by any other method. This study offers a rational tool for
      understanding the folding structure, kinetics, and pathway of two series of
      SCPNs. 

PMID- 25946316
TI  - Survival Rates in Trauma Patients Following Health Care Reform in Massachusetts.
AB  - IMPORTANCE: Massachusetts introduced health care reform (HCR) in 2006, expecting
      to expand health insurance coverage and improve outcomes. Because traumatic
      injury is a common acute condition with important health, disability, and
      economic consequences, examination of the effect of HCR on patients hospitalized
      following injury may help inform the national HCR debate. OBJECTIVE: To examine
      the effect of Massachusetts HCR on survival rates of injured patients. DESIGN,
      SETTING, AND PARTICIPANTS: Retrospective cohort study of 1,520,599 patients
      hospitalized following traumatic injury in Massachusetts or New York during the
      10 years (2002-2011) surrounding Massachusetts HCR using data from the State
      Inpatient Databases. We assessed the effect of HCR on mortality rates using a
      difference-in-differences approach to control for temporal trends in mortality.
      INTERVENTION: Health care reform in Massachusetts in 2006. MAIN OUTCOME AND
      MEASURE: Survival until hospital discharge. RESULTS: During the 10-year study
      period, the rates of uninsured trauma patients in Massachusetts decreased
      steadily from 14.9% in 2002 to 5.0.% in 2011. In New York, the rates of uninsured
      trauma patients fell from 14.9% in 2002 to 10.5% in 2011. The risk-adjusted
      difference-in-difference assessment revealed a transient increase of 604 excess
      deaths (95% CI, 419-790) in Massachusetts in the 3 years following implementation
      of HCR. CONCLUSIONS AND RELEVANCE: Health care reform did not affect health
      insurance coverage for patients hospitalized following injury but was associated
      with a transient increase in adjusted mortality rates. Reducing mortality rates
      for acutely injured patients may require more comprehensive interventions than
      simply promoting health insurance coverage through legislation.

PMID- 25946317
TI  - Graphitic Patterns on CVD Diamond Plate as Microheating/Thermometer Devices.
AB  - A simple compact temperature sensor and microheater in a wide temperature range
      has been developed, realizing a laser-patterned resistive structure on the
      surface of a synthetic polycrystalline diamond plate. Imaging and spectroscopy
      techniques used to investigate morphology, structure, and composition of the
      pattern showed that it incorporates different nondiamond carbon phases. Transport
      experiments revealed the semiconducting behavior of this microresistor. Thermal
      power measurements versus temperature are presented. A possible application of
      this device that may easily match compact experimental layouts avoiding both
      thermal anchoring offset and mechanical stress between sample and sensor is
      discussed. The patterned structure undergoes testing as a microthermometer,
      providing fast response and excellent stability versus time. It exhibits a good
      sensitivity that coupled to an easy calibration procedure minimizes errors and
      guarantees high accuracy. Plot of temperature versus input power of the resistive
      patterned line used as microheater shows a linear behavior in an extended
      temperature range. 

PMID- 25946320
TI  - Photodissociation of Methyl Iodide via Selected Vibrational Levels of the B
      ((2)E3/2)6s Rydberg State.
AB  - We have determined the I (2)P3/2 and (2)P1/2 branching fractions following the
      photodissociation of methyl iodide (CH3I) via a number of vibronic bands
      associated with the B ((2)E3/2)6s Rydberg state at excitation wavelengths between
      201.2 and 192.7 nm. Vacuum ultraviolet light at 118.2 nm was used to ionize both
      the product iodine atoms and the methyl radical cofragments, and velocity map ion
      imaging was used to determine the product translational energy distributions and
      angular distributions. The known relative photoionization cross sections for I
      (2)P3/2 and (2)P1/2 at 118.2 nm were used to determine the corresponding
      branching fractions. The results extend our earlier work at 193 nm by Xu et al.
      (J. Chem. Phys. 2013, 139, 214310), and complement the closely related work of
      Gonzalez et al. (J. Chem. Phys. 2011, 135, 021102). We find that for most of the
      excited vibronic levels of the B state studied, the I (2)P3/2 branching ratio is
      small, but nonzero, and that this channel is associated with internally excited
      CH3 radicals. The results are discussed in relation to the recent theoretical
      results of Alekseyev et al. (J. Chem. Phys. 2011, 134, 044303). 

PMID- 25946318
TI  - Classic Ras Proteins Promote Proliferation and Survival via Distinct
      Phosphoproteome Alterations in Neurofibromin-Null Malignant Peripheral Nerve
      Sheath Tumor Cells.
AB  - Neurofibromin, the tumor suppressor encoded by the neurofibromatosis type 1 (NF1)
      gene, potentially suppresses the activation of H-Ras, N-Ras, and K-Ras. However,
      it is not known whether these classic Ras proteins are hyperactivated in NF1-null
      nerve sheath tumors, how they contribute to tumorigenesis, and what signaling
      pathways mediate their effects. Here we show that H-Ras, N-Ras, and K-Ras are
      coexpressed with their activators (guanine nucleotide exchange factors) in
      neurofibromin-null malignant peripheral nerve sheath tumor (MPNST) cells, and
      that all 3 Ras proteins are activated. Dominant negative (DN) H-Ras, a pan
      inhibitor of the classic Ras family, inhibited MPNST proliferation and survival,
      but not migration. However, NF1-null MPNST cells were variably dependent on
      individual Ras proteins. In some lines, ablation of H-Ras, N-Ras, and/or K-Ras
      inhibited mitogenesis. In others, ablation of a single Ras protein had no effect
      on proliferation; in these lines, ablation of a single Ras protein resulted in
      compensatory increases in the activation and/or expression of other Ras proteins.
      Using mass spectrometry-based phosphoproteomics, we identified 7 signaling
      networks affecting morphology, proliferation, and survival that are regulated by
      DN H-Ras. Thus, neurofibromin loss activates multiple classic Ras proteins that
      promote proliferation and survival by regulating several distinct signaling
      cascades. 

PMID- 25946319
TI  - Core-like groups result in invalidation of identifying super-spreader by k-shell
      decomposition.
AB  - Identifying the most influential spreaders is an important issue in understanding
      and controlling spreading processes on complex networks. Recent studies showed
      that nodes located in the core of a network as identified by the k-shell
      decomposition are the most influential spreaders. However, through a great deal
      of numerical simulations, we observe that not in all real networks do nodes in
      high shells are very influential: in some networks the core nodes are the most
      influential which we call true core, while in others nodes in high shells, even
      the innermost core, are not good spreaders which we call core-like group. By
      analyzing the k-core structure of the networks, we find that the true core of a
      network links diversely to the shells of the network, while the core-like group
      links very locally within the group. For nodes in the core-like group, the k
      shell index cannot reflect their location importance in the network. We further
      introduce a measure based on the link diversity of shells to effectively
      distinguish the true core and core-like group, and identify core-like groups
      throughout the networks. Our findings help to better understand the structural
      features of real networks and influential nodes. 

PMID- 25946321
TI  - Correction: Entrapment bias of arthropods in Miocene amber revealed by trapping
      experiments in a tropical forest in Chiapas, Mexico.

PMID- 25946322
TI  - Evaluation of terrestrial plants extracts for uranium sorption and
      characterization of potent phytoconstituents.
AB  - Sorption capacity of four plants (Funaria hygrometrica, Musa acuminata, Brassica
      juncea and Helianthus annuus) extracts/fractions for uranium, a radionuclide was
      investigated by EDXRF and tracer studies. The maximum sorption capacity, i.e.,
      100% (complete sorption) was observed in case of Musa acuminata extract and
      fractions. Carbohydrate, proteins, phenolics and flavonoids contents in the
      active fraction (having maximum sorption capacity) were also determined. Further
      purification of the most active fraction provided three pure molecules, mannitol,
      sorbitol and oxo-linked potassium oxalate. The characterization of isolated
      molecules was achieved by using FTIR, NMR, GC-MS, MS-MS, and by single crystal
      XRD analysis. Of three molecules, oxo-linked potassium oxalate was observed to
      have 100% sorption activity. Possible binding mechanism of active molecule with
      the uranyl cation has been purposed. 

PMID- 25946323
TI  - Distribution of the ompA-types among ruminant and swine pneumonic strains of
      Pasteurella multocida exhibiting various cap-locus and toxA patterns.
AB  - Pasteurella multocida is an important pathogen in food-producing animals and
      numerous virulence genes have been identified in an attempt to elucidate the
      pathogenesis of pasteurellosis. Currently, some of these genes including the
      capsule biosynthesis genes, the toxA and the OMPs-encoding genes have been
      suggested as epidemiological markers. However, the number of studies concerning
      ruminant isolates is limited, while, no attempt has ever been made to investigate
      the existence of ompA sequence diversity among P. multocida isolates. The aim of
      the present study was the comparative analysis of 144 P. multocida pneumonic
      isolates obtained from sheep, goats, cattle and pigs by determining the
      distribution of the ompA-types in conjunction with the cap-locus and toxA
      patterns. The ompA genotypes of the isolates were determined using both a PCR
      RFLP method and DNA sequence analysis. The most prevalent capsule biosynthesis
      gene among the isolates was capA (86.1%); a noticeable, however, rate of capD
      positive isolates (38.6%) was found among the ovine isolates that had been
      associated primarily with the capsule type A in the past. Moreover, an
      unexpectedly high percentage of toxA-positive pneumonic isolates was noticed
      among small ruminants (93.2% and 85.7% in sheep and goats, respectively),
      indicating an important epidemiological role of toxigenic P. multocida for these
      species. Despite their great heterogeneity, certain ompA-genotypes were
      associated with specific host species, showing evidence of a host preference. The
      OmpA-based PCR-RFLP method developed proved to be a valuable tool in typing P.
      multocida strains. 

PMID- 25946324
TI  - Genetic evidence for the involvement of glycosyltransferase PdmQ and PdmS in
      biosynthesis of pradimicin from Actinomadura hibisca.
AB  - Pradimicins are potent antifungal antibiotics with effective inhibitory effects
      against HIV-1. Pradimicin A consists of an unusual
      dihydrobenzo[alpha]naphthacenequinone aglycone substituted with a combination of
      D-alanine and two sugar moieties. Detailed genetic studies revealed most steps in
      pradimicin A biosynthesis, but the glycosylation mechanism remained inconclusive.
      The biosynthetic gene cluster of pradimicin A contains two putative
      glycosyltransferases, pdmQ and pdmS. However, the exact involvement of each gene
      in biosynthesis and the particular steps required for precise structural
      modification was unknown. In this study, the exact role of each gene was
      evaluated by insertional inactivation and complementation studies. Analysis of
      the metabolite from both of the disruption mutants revealed abolishment of
      pradimicin A and complementation resulted in the recovery of production. After
      deletion of pdmQ, pradimicin B was found to accumulate, whereas deletion of pdmS
      resulted in the accumulation of aglycone of pradimicin. Together, these results
      suggest that pdmS is responsible for the attachment of thomosamine to form
      pradimicin B which in turn is glycosylated by pdmQ to form pradimicin A. These
      results allowed us to deduce the exact order of terminal tailoring by
      glycosylation and provided insight into the mechanism of pradimicin A
      biosynthesis.

PMID- 25946325
TI  - Stress response and expression of fluconazole resistance associated genes in the
      pathogenic yeast Candida glabrata deleted in the CgPDR16 gene.
AB  - In yeasts, the PDR16 gene encodes a phosphatidylinositol transfer protein which
      belongs to the Sec14 homologue (SFH) family and localizes to lipid droplets,
      microsomes and at the cell periphery. The loss of its function alters the lipid
      droplet metabolism and plasma membrane properties, and renders yeast cells more
      sensitive to azole antimycotics. In this study, the entire chromosomal CgPDR16
      ORF was replaced by the ScURA3 gene both in azole sensitive and azole resistant
      strains of Candida glabrata bearing a gain-of-function mutation in the CgPDR1
      gene, and their responses to different stresses were assessed. The CgPDR16
      deletion was found to sensitize the mutant strains to azole antifungals without
      changes in their osmo- and halotolerance. Fluconazole treated pdr16Delta mutant
      strains displayed a reduced expression of several genes involved in azole
      tolerance. The gain-of-function CgPDR1 allele as well as the cycloheximide and
      hydrogen peroxide treatments of cells enhanced the expression of the CgPDR16
      gene. The results indicate that CgPDR16 belongs to genes whose expression is
      induced by chemical and oxidative stresses. The loss of its function can
      attenuate the expression of drug efflux pump encoding genes that might also
      contribute to the decreased azole tolerance in pdr16Delta mutant cells. 

PMID- 25946326
TI  - Genetic mutations potentially cause two novel NCF1 splice variants up-regulated
      in the mammary gland, blood and neutrophil of cows infected by Escherichia coli.
AB  - Neutrophil cytosolic factor 1 (NCF1) plays a crucial role in host defense against
      microbial pathogens. In this study, we investigated the potential alternative
      splicing patterns, expression and splice-relevant single nucleotide polymorphisms
      (SNPs) of the bovine NCF1 gene to increase insights into its potential role
      against bovine mastitis caused by Escherichia coli infection. Using RT-PCR and
      clone sequencing methods, we found two novel splice variants designed as NCF1-TV1
      (retained intron 6) and NCF1-TV2 (retained part of intron 8), respectively,
      encoding two putative truncated proteins (239AA and 283AA). Two splice variants
      were drastically up-regulated in the mastitis-infected cows' mammary tissues,
      blood and neutrophils compared with these of healthy cows using real-time RT-PCR.
      Genomic sequencing analysis identified four novel SNPs g.10112 G>A, g.10766 T>C,
      SNPs g.12085 G>A and g.12430 T>C at the ends of intron 6 and intron 8 of NCF1.
      ESE motif predicted that the SNP (g.10766 T>C) might affect the binding with
      splicing-related factors and subsequently caused the production of aberrant
      splice variant NCF1-TV1, which is one of the potential reasons that the
      functional SNP was associated with increased milk somatic cell score in cow. Our
      results would help in better understanding the NCF1 gene function in the process
      against pathogen infection, and the effect of splicing-related SNP on the
      production of aberrant splice variant and careful functional characterization in
      dairy cattle. 

PMID- 25946327
TI  - Nocardiopsis species: Incidence, ecological roles and adaptations.
AB  - Members of the genus Nocardiopsis are ecologically versatile and
      biotechnologically important. They produce a variety of bioactive compounds such
      as antimicrobial agents, anticancer substances, tumor inducers, toxins and
      immunomodulators. They also secrete novel extracellular enzymes such as amylases,
      chitinases, cellulases, beta-glucanases, inulinases, xylanases and proteases.
      Nocardiopsis species are aerobic, Gram-positive, non-acid-fast, catalase-positive
      actinomycetes with nocardioform substrate mycelia and their aerial mycelia bear
      long chains of spores. Their DNA possesses high contents of guanine and cytosine.
      There is a marked variation in properties of the isolates obtained from different
      ecological niches and their products. An important feature of several species is
      their halophilic or halotolerant nature. They are associated with a variety of
      marine and terrestrial biological forms wherein they produce antibiotics and
      toxins that help their hosts in evading pathogens and predators. Two Nocardiopsis
      species, namely, N. dassonvillei and N. synnemataformans (among the thirty nine
      reported ones) are opportunistic human pathogens and cause mycetoma, suppurative
      infections and abscesses. Nocardiopsis species are present in some plants (as
      endophytes or surface microflora) and their rhizospheres. Here, they are reported
      to produce enzymes such as alpha-amylases and antifungal agents that are
      effective in warding-off plant pathogens. They are prevalent as free-living
      entities in terrestrial locales, indoor locations, marine ecosystems and
      hypersaline habitats on account of their salt-, alkali- and desiccation-resistant
      behavior. In such natural locations, Nocardiopsis species mainly help in
      recycling organic compounds. Survival under these diverse conditions is mediated
      by the production of extracellular enzymes, antibiotics, surfactants, and the
      accumulation of compatible solutes. The accommodative genomic features of
      Nocardiopsis species support their existence under the diverse conditions where
      they prevail. 

PMID- 25946328
TI  - Isolation and identification of bacteria to improve the strength of concrete.
AB  - The objective of this research work is to isolate and identify calcite
      precipitating bacteria and to check the suitability of these bacteria for use in
      concrete to improve its strength. Bacteria to be incorporated in concrete should
      be alkali resistant to endure the high pH of concrete and endospore forming to
      withstand the mechanical stresses induced in concrete during mixing. They must
      exhibit high urease activity to precipitate calcium carbonate in the form of
      calcite. Bacterial strains were isolated from alkaline soil samples of a cement
      factory and were tested for urease activity, potential to form endospores and
      precipitation of calcium carbonate. Based on these results, three isolates were
      selected and identified by 16S rRNA gene sequencing. They were identified as
      Bacillus megaterium BSKAU, Bacillus licheniformis BSKNAU and Bacillus flexus
      BSKNAU. The results were compared with B. megaterium MTCC 1684 obtained from
      Microbial Type Culture Collection and Gene Bank, Chandigarh, India. Experimental
      work was carried out to assess the influence of bacteria on the compressive
      strength and tests revealed that bacterial concrete specimens showed enhancement
      in compressive strength. The efficiency of bacteria toward crack healing was also
      tested. Substantial increase in strength and complete healing of cracks was
      observed in concrete specimens cast with B. megaterium BSKAU, B. licheniformis
      BSKNAU and B. megaterium MTCC 1684. This indicates the suitability of these
      bacterial strains for use in concrete. The enhancement of strength and healing of
      cracks can be attributed to the filling of cracks in concrete by calcite which
      was visualized by scanning electron microscope. 

PMID- 25946329
TI  - Structural and functional studies of BapC protein of Bordetella pertussis.
AB  - Bordetella pertussis, the causative agent of whooping cough, attaches to mucosal
      surface in upper respiratory tract, where it produces a variety of surface
      associated and secreted autotransporter molecules among others. In this study we
      have cloned newly identified member of autotransporter family BapC (B. pertussis
      autotransporter protein C); expressed it in Escherichia coli and characterized it
      for its different properties. We have also raised antisera to BapC protein; the
      antisera were used in immunofluorescence assay to determine the surface
      association of the protein. Results suggest that BapC in B. pertussis Taberman
      parent is surface exposed when compared with the respective BapC mutant. The
      neutralizing effect of anti-BapC serum was also evaluated in the presence of
      active complement proteins and results suggest that antiserum can potentiate the
      killing of B. pertussis cells in the presence of added source of complement.
      Structure of the protein was also studied, both alpha and beta domains of the
      protein were modeled, beta domain exhibits typical transmembrane beta-barrel
      porin topology whereas alpha domain behaves as a characteristic bacterial
      autotransporter passenger domain. 

PMID- 25946333
TI  - The Inner Nuclear Membrane Protein Nemp1 Is a New Type of RanGTP-Binding Protein
      in Eukaryotes.
AB  - The inner nuclear membrane (INM) protein Nemp1/TMEM194A has previously been
      suggested to be involved in eye development in Xenopus, and contains two
      evolutionarily conserved sequences in the transmembrane domains (TMs) and the C
      terminal region, named region A and region B, respectively. To elucidate the
      molecular nature of Nemp1, we analyzed its interacting proteins through those
      conserved regions. First, we found that Nemp1 interacts with itself and lamin
      through the TMs and region A, respectively. Colocalization of Nemp1 and lamin at
      the INM suggests that the interaction with lamin participates in the INM
      localization of Nemp1. Secondly, through yeast two-hybrid screening using region
      B as bait, we identified the small GTPase Ran as a probable Nemp1-binding
      partner. GST pulldown and co-immunoprecipitation assays using region B and Ran
      mutants revealed that region B binds directly to the GTP-bound Ran through its
      effector domain. Immunostaining experiments using transfected COS-7 cells
      revealed that full-length Nemp1 recruits Ran near the nuclear envelope,
      suggesting a role for Nemp1 in the accumulation of RanGTP at the nuclear
      periphery. At the neurula-to-tailbud stages of Xenopus embryos, nemp1 expression
      overlapped with ran in several regions including the eye vesicles. Co-knockdown
      using antisense morpholino oligos for nemp1 and ran caused reduction of cell
      densities and severe eye defects more strongly than either single knockdown
      alone, suggesting their functional interaction. Finally we show that Arabidopsis
      thaliana Nemp1-orthologous proteins interact with A. thaliana Ran, suggesting
      their evolutionally conserved physical and functional interactions possibly in
      basic cellular functions including nuclear transportation. Taken together, we
      conclude that Nemp1 represents a new type of RanGTP-binding protein. 

PMID- 25946330
TI  - SYK regulates macrophage MHC-II expression via activation of autophagy in
      response to oxidized LDL.
AB  - Adaptive immunity, which plays an important role in the development of
      atherosclerosis, is mediated by major histocompatibility complex (MHC)-dependent
      antigen presentation. In atherosclerotic lesions, macrophages constitute an
      important class of antigen-presenting cells that activate adaptive immune
      responses to oxidized low-density lipoprotein (OxLDL). It has been reported that
      autophagy regulates adaptive immune responses by enhancing antigen presentation
      to MHC class II (MHC-II). In a previous study, we have demonstrated that SYK
      (spleen tyrosine kinase) regulates generation of reactive oxygen species (ROS)
      and activation of MAPK8/JNK1 in macrophages. Because ROS and MAPK8 are known to
      regulate autophagy, in this study we investigated the role of SYK in autophagy,
      MHC-II expression and adaptive immune response to OxLDL. We demonstrate that
      OxLDL induces autophagosome formation, MHC-II expression, and phosphorylation of
      SYK in macrophages. Gene knockout and pharmacological inhibitors of NOX2 and
      MAPK8 reduced OxLDL-induced autophagy. Using bone marrow-derived macrophages
      isolated from wild-type and myeloid-specific SYK knockout mice, we demonstrate
      that SYK regulates OxLDL-induced ROS generation, MAPK8 activation, BECN1-BCL2
      dissociation, autophagosome formation and presentation of OxLDL-derived antigens
      to CD4(+) T cells. ldlr(-/-) syk(-/-) mice fed a high-fat diet produced lower
      levels of IgG to malondialdehyde (MDA)-LDL, malondialdehyde-acetaldehyde (MAA)
      LDL, and OxLDL compared to ldlr(-/-) mice. These results provide new insights
      into the mechanisms by which SYK regulates MHC-II expression via autophagy in
      macrophages and may contribute to regulation of adaptive immune responses in
      atherosclerosis. 

PMID- 25946334
TI  - Temporal dynamics of stress-induced alternations of intrinsic amygdala
      connectivity and neuroendocrine levels.
AB  - Stress-induced changes in functional brain connectivity have been linked to the
      etiology of stress-related disorders. Resting state functional connectivity
      (rsFC) is especially informative in characterizing the temporal trajectory of
      glucocorticoids during stress adaptation. Using the imaging Maastricht Acute
      Stress Test (iMAST), we induced acute stress in 39 healthy volunteers and
      monitored the neuroendocrine stress levels during three runs of resting state
      functional magnetic resonance imaging (rs-fMRI): before (run 1), immediately
      following (run 2), and 30 min after acute stress (run 3). The iMAST resulted in
      strong increases in cortisol levels. Whole-brain analysis revealed that acute
      stress (run 2 - 1) was characterized by changes in connectivity of the amygdala
      with the ventrolateral prefrontal cortex (vlPFC), ventral posterior cingulate
      cortex (PCC), cuneus, parahippocampal gyrus, and culmen. Additionally, cortisol
      responders were characterized by enhanced amygdala - medial prefrontal cortex
      (mPFC) connectivity. Stress recovery (run 3 - 2) was characterized by altered
      amygdala connectivity with the dorsolateral prefrontal cortex (dlPFC), ventral
      and dorsal anterior cingulate cortex (ACC), anterior hippocampal complex, cuneus,
      and presupplementary motor area (preSMA). Opposite to non-responders, cortisol
      responders were characterized by enhanced amygdala connectivity with the anterior
      hippocampal complex and parahippocampal gyrus, and reduced connectivity with left
      dlPFC, dACC, and culmen during early recovery. Acute stress responding and
      recovery are thus associated with changes in the functional connectivity of the
      amygdala network. Our findings show that these changes may be regulated via
      stress-induced neuroendocrine levels. Defining stress-induced neuronal network
      changes is pertinent to developing treatments that target abnormal neuronal
      activity.

PMID- 25946335
TI  - Competition and habitat quality influence age and sex distribution in wintering
      rusty blackbirds.
AB  - Bird habitat quality is often inferred from species abundance measures during the
      breeding and non-breeding season and used for conservation management decisions.
      However, during the non-breeding season age and sex classes often occupy
      different habitats which suggest a need for more habitat-specific data. Rusty
      Blackbird (Euphagus carolinus) is a forested wetland specialist wintering in
      bottomland hardwood forests in the south-eastern U. S. and belongs to the most
      steeply declining songbirds in the U.S. Little information is available to
      support priority birds such as the Rusty Blackbird wintering in this threatened
      habitat. We assessed age and sex distribution and body condition of Rusty
      Blackbirds among the three major habitats used by this species in the Lower
      Mississippi Alluvial Valley and also measured food availability. Overall, pecan
      groves had the highest biomass mainly driven by the amount of nuts. Invertebrate
      biomass was highest in forests but contributed only a small percentage to overall
      biomass. Age and sex classes were unevenly distributed among habitats with adult
      males primarily occupying pecan groves containing the highest nut biomass,
      females being found in forests which had the lowest nut biomass and young males
      primarily staying in forest fragments along creeks which had intermediate nut
      biomass. Males were in better body condition than females and were in slightly
      better condition in pecan groves. The results suggest that adult males occupy the
      highest quality habitat and may competitively exclude the other age and sex
      classes. 

PMID- 25946338
TI  - Host-specific toxins and chemical structures from alternaria species.

PMID- 25946336
TI  - Evaluation of a Phylogenetic Marker Based on Genomic Segment B of Infectious
      Bursal Disease Virus: Facilitating a Feasible Incorporation of this Segment to
      the Molecular Epidemiology Studies for this Viral Agent.
AB  - BACKGROUND: Infectious bursal disease (IBD) is a highly contagious and acute
      viral disease, which has caused high mortality rates in birds and considerable
      economic losses in different parts of the world for more than two decades and it
      still represents a considerable threat to poultry. The current study was designed
      to rigorously measure the reliability of a phylogenetic marker included into
      segment B. This marker can facilitate molecular epidemiology studies,
      incorporating this segment of the viral genome, to better explain the links
      between emergence, spreading and maintenance of the very virulent IBD virus
      (vvIBDV) strains worldwide. METHODOLOGY/PRINCIPAL FINDINGS: Sequences of the
      segment B gene from IBDV strains isolated from diverse geographic locations were
      obtained from the GenBank Database; Cuban sequences were obtained in the current
      work. A phylogenetic marker named B-marker was assessed by different phylogenetic
      principles such as saturation of substitution, phylogenetic noise and high
      consistency. This last parameter is based on the ability of B-marker to
      reconstruct the same topology as the complete segment B of the viral genome. From
      the results obtained from B-marker, demographic history for both main lineages of
      IBDV regarding segment B was performed by Bayesian skyline plot analysis.
      Phylogenetic analysis for both segments of IBDV genome was also performed,
      revealing the presence of a natural reassortant strain with segment A from vvIBDV
      strains and segment B from non-vvIBDV strains within Cuban IBDV population.
      CONCLUSIONS/SIGNIFICANCE: This study contributes to a better understanding of the
      emergence of vvIBDV strains, describing molecular epidemiology of IBDV using the
      state-of-the-art methodology concerning phylogenetic reconstruction. This study
      also revealed the presence of a novel natural reassorted strain as possible
      manifest of change in the genetic structure and stability of the vvIBDV strains.
      Therefore, it highlights the need to obtain information about both genome
      segments of IBDV for molecular epidemiology studies.

PMID- 25946337
TI  - Deconvoluting Protein (Un)folding Structural Ensembles Using X-Ray Scattering,
      Nuclear Magnetic Resonance Spectroscopy and Molecular Dynamics Simulation.
AB  - The folding and unfolding of protein domains is an apparently cooperative
      process, but transient intermediates have been detected in some cases. Such
      (un)folding intermediates are challenging to investigate structurally as they are
      typically not long-lived and their role in the (un)folding reaction has often
      been questioned. One of the most well studied (un)folding pathways is that of
      Drosophila melanogaster Engrailed homeodomain (EnHD): this 61-residue protein
      forms a three helix bundle in the native state and folds via a helical
      intermediate. Here we used molecular dynamics simulations to derive sample
      conformations of EnHD in the native, intermediate, and unfolded states and
      selected the relevant structural clusters by comparing to small/wide angle X-ray
      scattering data at four different temperatures. The results are corroborated
      using residual dipolar couplings determined by NMR spectroscopy. Our results
      agree well with the previously proposed (un)folding pathway. However, they also
      suggest that the fully unfolded state is present at a low fraction throughout the
      investigated temperature interval, and that the (un)folding intermediate is
      highly populated at the thermal midpoint in line with the view that this
      intermediate can be regarded to be the denatured state under physiological
      conditions. Further, the combination of ensemble structural techniques with MD
      allows for determination of structures and populations of multiple
      interconverting structures in solution. 

PMID- 25946339
TI  - Trends and threshold exceedances analysis of airborne pollen concentrations in
      Metropolitan Santiago Chile.
AB  - Pollen is one of the primary causes of allergic rhinoconjunctivitis in urban
      centers. In the present study, the concentrations of 39 different pollens in the
      Santiago de Chile metropolitan area over the period 2009-2013 are characterized.
      The pollen was monitored daily using Burkard volumetric equipment. The
      contribution of each type of pollen and the corresponding time trends are
      evaluated. The concentrations of the pollens are compared with the established
      threshold levels for the protection of human health. The results show that the
      total amount of pollen grains originating from trees, grasses, weeds and
      indeterminate sources throughout the period of the study was 258,496 grains m-3,
      with an annual average of 51,699 +/- 3,906 grains m-3 year-1. The primary source
      of pollen is Platanus orientalis, which produces 61.8% of the analyzed pollen.
      Grass pollen is the third primary component of the analyzed pollen, with a
      contribution of 5.82%. Among the weeds, the presence of Urticacea (3.74%) is
      remarkable. The pollination pattern of the trees is monophasic, and the grasses
      have a biphasic pattern. The trends indicate that the total pollen and tree
      pollen do not present a time trend that is statistically significant throughout
      the period of the study, whereas the grass pollen and weed pollen concentrations
      in the environment present a statistically significant decreasing trend. The
      cause of this decrease is unclear. The pollen load has doubled over the past
      decade. When the observed concentrations of the pollens were compared with the
      corresponding threshold levels, the results indicated that over the period of the
      study, the pollen concentrations were at moderate, high and very high levels for
      an average of 293 days per year. Systematic counts of the pollen grains are an
      essential method for diagnosing and treating patients with pollinosis and for
      developing forestation and urban planning strategies. 

PMID- 25946340
TI  - Instrumentation on multi-scaled scattering of bio-macromolecular solutions.
AB  - The design, construction and initial tests on a combined laser light scattering
      and synchrotron X-ray scattering instrument can cover studies of length scales
      from atomic sizes in Angstroms to microns and dynamics from microseconds to
      seconds are presented. In addition to static light scattering (SLS), dynamic
      light scattering (DLS), small angle X-ray scattering (SAXS) and wide angle X-ray
      diffraction (WAXD), the light scattering instrument is being developed to carry
      out studies in mildly turbid solutions, in the presence of multiple scattering.
      Three-dimensional photon cross correlation function (3D-PCCF) measurements have
      been introduced to couple with synchrotron X-ray scattering to study the
      structure, size and dynamics of macromolecules in solution. 

PMID- 25946341
TI  - Nitrogen Removal Characteristics of a Newly Isolated Indigenous Aerobic
      Denitrifier from Oligotrophic Drinking Water Reservoir, Zoogloea sp. N299.
AB  - Nitrogen is considered to be one of the most widespread pollutants leading to
      eutrophication of freshwater ecosystems, especially in drinking water reservoirs.
      In this study, an oligotrophic aerobic denitrifier was isolated from drinking
      water reservoir sediment. Nitrogen removal performance was explored. The strain
      was identified by 16S rRNA gene sequence analysis as Zoogloea sp. N299. This
      species exhibits a periplasmic nitrate reductase gene (napA). Its specific growth
      rate was 0.22 h-1. Obvious denitrification and perfect nitrogen removal
      performances occurred when cultured in nitrate and nitrite mediums, at rates of
      75.53%+/-1.69% and 58.65%+/-0.61%, respectively. The ammonia removal rate reached
      44.12%+/-1.61% in ammonia medium. Zoogloea sp. N299 was inoculated into
      sterilized and unsterilized reservoir source waters with a dissolved oxygen level
      of 5-9 mg/L, pH 8-9, and C/N 1.14:1. The total nitrogen removal rate reached
      46.41%+/-3.17% (sterilized) and 44.88%+/-4.31% (unsterilized). The cell optical
      density suggested the strain could survive in oligotrophic drinking water
      reservoir water conditions and perform nitrogen removal. Sodium acetate was the
      most favorable carbon source for nitrogen removal by strain N299 (p<0.05). High
      C/N was beneficial for nitrate reduction (p<0.05). The nitrate removal
      efficiencies showed no significant differences among the tested inoculums dosage
      (p>0.05). Furthermore, strain N299 could efficiently remove nitrate at neutral
      and slightly alkaline and low temperature conditions. These results, therefore,
      demonstrate that Zoogloea sp. N299 has high removal characteristics, and can be
      used as a nitrogen removal microbial inoculum with simultaneous aerobic
      nitrification and denitrification in a micro-polluted reservoir water ecosystem.

PMID- 25946342
TI  - Autistic children exhibit decreased levels of essential Fatty acids in red blood
      cells.
AB  - Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) are essential
      nutrients for brain development and function. However, whether or not the levels
      of these fatty acids are altered in individuals with autism remains debatable. In
      this study, we compared the fatty acid contents between 121 autistic patients and
      110 non-autistic, non-developmentally delayed controls, aged 3-17. Analysis of
      the fatty acid composition of red blood cell (RBC) membrane phospholipids showed
      that the percentage of total PUFA was lower in autistic patients than in
      controls; levels of n-6 arachidonic acid (AA) and n-3 docosahexaenoic acid (DHA)
      were particularly decreased (p<0.001). In addition, plasma levels of the pro
      inflammatory AA metabolite prostaglandin E2 (PGE2) were higher in a subset of the
      autistic participants (n=20) compared to controls. Our study demonstrates an
      alteration in the PUFA profile and increased production of a PUFA-derived
      metabolite in autistic patients, supporting the hypothesis that abnormal lipid
      metabolism is implicated in autism.

PMID- 25946343
TI  - Peripheral Blood Lymphocyte Subsets (CD4+, CD8+ T Cells, NK Cells) in Patients
      with Cardiovascular and Neurological Complications after Carotid Endarterectomy.
AB  - BACKGROUND: The aim of the study was to evaluate the differences in the
      circulating immune cells' subgroups after the atherosclerotic plaque removal in
      patients presenting with postoperative complications as compared to the patients
      without complications after carotid endarterectomy (CEA). METHODS: Patients with
      significant carotid atherosclerosis (n=124, age range: 44 to 87 years) who
      underwent CEA were enrolled in a prospective study. The immunology study using
      flow cytometry was performed to determine the percentages of peripheral blood T
      cells (CD4+, CD8+, Treg-CD4+/CD25+) and NK (natural killer) cells before and
      after the procedure. The data were expressed as the percentage of total
      lymphocytes+/-the standard error of mean. RESULTS: The mean percentage of
      lymphocytes (61.54%+/-17.50% vs. 71.82%+/-9.68%, p=0.030) and CD4 T lymphocytes
      (T helper, 38.13%+/-13.78% vs. 48.39%+/-10.24%, p=0.027) was significantly lower
      six hours after CEA in patients with postoperative 30-day cardiovascular and
      neurological complications as compared to the group without complications. On the
      other hand the mean NK level in the group with complications was significantly
      higher (21.61%+/-9.00% vs. 15.80%+/-9.31%, p=0.048). CONCLUSIONS: The results of
      this study suggest that after carotid endarterectomy the percentages of
      circulating immune cells subsets differ in patients with and without
      postoperative complications.

PMID- 25946344
TI  - Histomorphometric evaluation of the small coronary arteries in rats exposed to
      industrial noise.
AB  - Morphological changes induced by industrial noise (IN) have been experimentally
      observed in several organs. Histological observations of the coronary arteries
      showed prominent perivascular tissue and fibrosis among IN-exposed rats. The
      effects on the small arteries are unknown. OBJECTIVE: To evaluate the
      histomorphometric changes induced by IN on rat heart small arteries. METHODS:
      Twenty Wistar rats exposed to IN during a maximum period of seven months and 20
      age-matched controls were studied. Hearts were transversely sectioned from
      ventricular apex to atria and a mid-ventricular fragment was selected for
      analysis. The histological images were obtained with an optical microscope using
      400* magnifications. A total of 634 arterial vessels (298 IN-exposed and 336
      controls) were selected. The mean lumen-to-vessel wall (L/W) and mean vessel wall
      to-perivascular tissue (W/P) ratios were calculated using image J software.
      RESULTS: There were no differences between exposed and control animals in their
      L/W ratios (p=0.687) and time variations in this ratio were non-significant
      (p=0.110). In contrast, exposed animals showed lower W/P ratios than control
      animals (p<0.001), with significant time variations (p=0.004). CONCLUSIONS:
      Industrial noise induced an increase in the perivascular tissue of rat small
      coronary arteries, with significant development of periarterial fibrosis.

PMID- 25946345
TI  - Effect of gamma-Cyclodextrin Inclusion Complex on the Absorption of R-alpha
      Lipoic Acid in Rats.
AB  - R-alpha-lipoic acid (RLA) is an endogenous organic acid, and works as a cofactor
      for mitochondrial enzymes and as a kind of antioxidant. Inclusion complexes of
      RLA with alpha-, beta- or gamma-cyclodextrins (CD) were prepared and orally
      administered as a suspension to rats. Among them, RLA/gamma-CD showed the highest
      plasma exposure, and its area under the plasma concentration-time curve (AUC) of
      RLA was 2.2 times higher than that after oral administration of non-inclusion
      RLA. On the other hand, the AUC after oral administration of non-inclusion RLA
      and RLA/gamma-CD to pylorus-ligated rats did not differ. However, the AUC after
      intraduodenal administration of RLA/gamma-CD was 5.1 times higher than that of
      non-inclusion RLA, and was almost comparable to the AUC after intraduodenal
      administration of RLA-Na solution. Furthermore, the AUC after intraduodenal
      administration of RLA/gamma-CD was not affected by biliary ligation or co
      administration of an amylase inhibitor. These findings demonstrated that RLA was
      absorbed from the small intestine effectively when orally administered as a gamma
      CD inclusion complex, which could be easily dissolved in the lumen of the
      intestine. In conclusion, gamma-CD inclusion complex is an appropriate
      formulation for supplying RLA as a drug or nutritional supplement with respect to
      absorption. 

PMID- 25946346
TI  - Discovery of ML358, a Selective Small Molecule Inhibitor of the SKN-1 Pathway
      Involved in Drug Detoxification and Resistance in Nematodes.
AB  - Nematodes parasitize ~1/3 of humans worldwide, and effective treatment via
      administration of anthelmintics is threatened by growing resistance to current
      therapies. The nematode transcription factor SKN-1 is essential for development
      of embryos and upregulates the expression of genes that result in modification,
      conjugation, and export of xenobiotics, which can promote resistance. Distinct
      differences in regulation and DNA binding relative to mammalian Nrf2 make SKN-1 a
      promising and selective target for the development of anthelmintics with a novel
      mode of action that targets stress resistance and drug detoxification. We report
      17 (ML358), a first in class small molecule inhibitor of the SKN-1 pathway.
      Compound 17 resulted from a vanillamine-derived hit identified by high throughput
      screening that was advanced through analog synthesis and structure-activity
      studies. Compound 17 is a potent (IC50 = 0.24 MUM, Emax = 100%) and selective
      inhibitor of the SKN-1 pathway and sensitizes the model nematode C. elegans to
      oxidants and anthelmintics. Compound 17 is inactive against Nrf2, the homologous
      mammalian detoxification pathway, and is not toxic to C. elegans (LC50 > 64 MUM)
      and Fa2N-4 immortalized human hepatocytes (LC50 > 5.0 MUM). In addition, 17
      exhibits good solubility, permeability, and chemical and metabolic stability in
      human and mouse liver microsomes. Therefore, 17 is a valuable probe to study
      regulation and function of SKN-1 in vivo. By selective targeting of the SKN-1
      pathway, 17 could potentially lead to drug candidates that may be used as
      adjuvants to increase the efficacy and useful life of current anthelmintics. 

PMID- 25946347
TI  - Transitioning from 'stopping' to 'ending' the tuberculosis epidemic.

PMID- 25946348
TI  - Reducing relapse in tuberculosis treatment: is it time to reassess WHO treatment
      guidelines?

PMID- 25946349
TI  - Time to be a bit more 'surgical' in our management of children with drug
      resistant tuberculosis.

PMID- 25946350
TI  - Adaptive clinical trials in tuberculosis: applications, challenges and solutions.
AB  - Drug development for tuberculosis (TB) faces numerous practical obstacles,
      including the need for combination treatment with at least three drugs, reliance
      on possibly unrepresentative animal models which may not reproduce key features
      of human disease and the lack of a well-validated surrogate endpoint for stable
      cure. Pivotal Phase III trials are large, lengthy and expensive, and the funding
      and capacity to conduct them are limited worldwide. More rational methods for the
      selection of priority regimens for Phase III are urgently needed to avoid costly
      late-stage failures. We examine the suitability of adaptive clinical trial
      designs for drug development in TB, focusing on designs for Phase IIB and III
      trials, where we believe the biggest gains in efficiency can be made. Key areas
      that may be addressed by such designs are improvements in the selection of doses
      and combinations of drugs in early clinical development and in maximising the
      power of confirmatory trials in multidrug-resistant TB, where patient numbers and
      complexity pose practical limitations. We encourage trialists and regulators in
      this area to consider the advantages that may be offered by these designs and
      their potential to more effectively and rapidly identify better treatment
      regimens for TB patients worldwide. 

PMID- 25946351
TI  - Could repeated prevalence surveys lead to decreasing tuberculosis prevalence in a
      community?
AB  - SETTING: Tiruvallur District, South India, where one baseline tuberculosis (TB)
      disease prevalence survey followed by three repeat prevalence surveys were
      conducted every 2.5 years between 1999 and 2008, and where the DOTS strategy was
      implemented in 1999. OBJECTIVE: To rule out the possibility that the observed
      decline in TB prevalence was influenced by conducting repeat prevalence surveys,
      we compared the findings from two surveys: the third repeat survey conducted in
      2006-2008 and an independent single survey in a neighbouring area conducted in
      2008-2009. DESIGN: An independent survey was conducted to estimate the prevalence
      of TB in the same district in 2008-2009 using a different set of villages and
      employing repeat survey methodology. The independent survey findings were
      compared with those of the third repeat survey. RESULTS: The estimated prevalence
      rate of culture- and smear-positive TB was respectively 401 per 100,000 and 186
      per 100,000 population in the third repeat survey area. The corresponding rates
      were 340 and 184/100,000 in the independent survey area. The difference in
      prevalence was not significant (culture P = 0.09; smear P = 0.93). CONCLUSION:
      The estimated prevalence rates in the two different sample survey areas were
      comparable, indicating that the repeated prevalence surveys in the study area did
      not influence the observed decline in TB disease prevalence.

PMID- 25946352
TI  - Health care-seeking behaviour among people with cough in Tanzania: findings from
      a tuberculosis prevalence survey.
AB  - SETTING: The study was conducted within a nation-wide population-based
      tuberculosis (TB) prevalence survey in the adult population in Tanzania.
      OBJECTIVE: To assess the health care-seeking behaviour of coughers presumed to
      have TB. DESIGN: A survey in which participants were screened for TB using a
      symptom questionnaire and chest X-ray (CXR). Those with cough of ? 2 weeks and/or
      who were coughing blood were interviewed about their health care-seeking
      behaviour and socio-demographic and clinical factors. RESULTS: Of 3388 people
      with presumptive TB, 31.0% (1051/3388) had sought treatment for their symptoms.
      Of these, about 42% (445/1051) sought care at sites with TB diagnostic capacity,
      where sputum examination was performed in 37.1% (165/445) and CXR in 28.1%
      (125/445). In sites with limited TB diagnostic capacity, fewer than 1% were
      referred for sputum examination or CXR. Individuals with additional symptoms were
      more likely to seek treatment. Knowledge about TB was significantly associated
      with care seeking at sites with TB diagnostic capacity. CONCLUSIONS: A third of
      the persons with cough symptoms consistent with TB had sought health care. About
      42% sought care in sites with TB diagnostic capacity, but most did not undergo TB
      diagnostic procedures, precluding a timely diagnosis.

PMID- 25946353
TI  - High incidence of latent tuberculous infection among South African health
      workers: an urgent call for action.
AB  - SETTING: In South Africa, health care workers (HCWs) are at two-fold greater risk
      of acquiring tuberculosis (TB) disease than the general population. Few studies
      have evaluated the risk of incident tuberculous infection. OBJECTIVE: To
      determine the incidence and risk factors for latent tuberculous infection (LTBI)
      among HCWs and to compare the results of the interferon-gamma release assay
      (IGRA) with those of the tuberculin skin test (TST). DESIGN: HCWs, including
      medical students, underwent a TST and human immunodeficiency virus (HIV) and IGRA
      testing at baseline and 12 months, and IGRA at 6 months. The participants kept 12
      month TB exposure logs. RESULTS: Among 199 participants (150 [76%] females,
      median age 31 years [range 20-61]), incident LTBI was documented using IGRA in
      25/97 (26%; incident rate 29 cases/100 person-years [py], 95%CI 20-44) and using
      TST in 25/93 (27%; incident rate 29 cases/100 py, 95%CI 19-42). Agreement between
      TST and IGRA was poor (44.8%, kappa = 0.23). Higher annual exposure to TB cases
      was reported among persons with LTBI than in those who were persistently IGRA
      negative (81 cases, 95%CI 61-102 vs. 50 cases, 95%CI 43-57, P < 0.01).
      CONCLUSION: The high LTBI incidence and the association of incident LTBI with
      annual TB caseload among HCWs indicate that more effective TB infection control
      should be implemented in South African health care facilities.

PMID- 25946354
TI  - Can the number of patients with presumptive tuberculosis lost in the general
      health services in Pakistan be reduced?
AB  - The frequency of patients with presumptive tuberculosis (TB) who are not
      investigated by sputum smear microscopy is unknown in Pakistan. Using a simple
      intervention comparing patient and laboratory registers, patients with
      presumptive TB were identified in two districts from July to December 2013, a
      list of missing patients was prepared and the patients traced. The intervention
      significantly reduced the number of patients with presumptive TB lost, from 8.5%
      before the intervention to 6.9% after. A systematic comparison of out-patient and
      laboratory registers, followed by tracing missing persons, can reduce the
      proportion of patients with presumptive TB lost before diagnosis. 

PMID- 25946355
TI  - Success of community-based directly observed anti-tuberculosis treatment in
      Mongolia.
AB  - BACKGROUND: Many countries restrict access to directly observed therapy (DOT) for
      tuberculosis (TB) to government health facilities. More innovative approaches are
      required to reduce non-adherence, improve patient outcomes and limit the risk of
      selecting drug-resistant strains. METHODS: We performed a retrospective cohort
      study in sputum smear-positive patients treated with community-based DOT (home
      based DOT or 'lunch' DOT, whereby DOT is provided with a free daily meal once
      sputum smear conversion has been documented), and conventional clinic-based DOT
      in Ulaanbaatar, the capital of Mongolia, in 2010-2011. We compared treatment
      success using community-based home DOT vs. conventional clinic DOT and describe
      treatment completion rates using lunch DOT. RESULTS: The overall treatment
      success among new sputum smear-positive TB patients was 85.1% (1505/1768).
      Patients receiving community DOT had higher cure rates (294/327, 89.9% vs.
      1112/1441, 77.2%; aOR 2.66, 95%CI 1.81-3.90) and higher treatment success
      (306/327, 93.6% vs. 1199/1441, 83.2%; aOR 2.95, 95%CI 1.85-4.71, P < 0.001) than
      those treated with clinic DOT. Apart from one death, treatment completion was
      100% among patients who received lunch DOT after sputum smear conversion.
      CONCLUSIONS: Community DOT improved treatment success in Ulaanbaatar, Mongolia.
      It should now be scaled up to be made available for more patients and in all
      regions of the country.

PMID- 25946357
TI  - The fourth national anti-tuberculosis drug resistance survey in Viet Nam.
AB  - SETTING: Viet Nam's Fourth National Anti-Tuberculosis Drug Resistance Survey was
      conducted in 2011. OBJECTIVE: To determine the prevalence of resistance to the
      four main first-line anti-tuberculosis drugs in Viet Nam. METHODS: Eighty
      clusters were selected using a probability proportion to size approach. Drug
      susceptibility testing (DST) against the four main first-line anti-tuberculosis
      drugs was performed. RESULTS: A total of 1629 smear-positive tuberculosis (TB)
      patients were eligible for culture. Of these, DST results were available for 1312
      patients, including 1105 new TB cases, 195 previously treated TB cases and 12
      cases with an unknown treatment history. The proportion of cases with resistance
      to any drug was 32.7% (95%CI 29.1-36.5) among new cases and 54.2% (95%CI 44.3
      63.7) among previously treated cases. The proportion of multidrug-resistant TB
      (MDR-TB) cases was 4.0% (95%CI 2.5-5.4) in new cases and 23.3 (95%CI 16.7-29.9)
      in previously treated cases. CONCLUSIONS: The fourth drug resistance survey in
      Viet Nam found that the proportion of MDR-TB among new and previously treated
      cases was not significantly different from that in the 2005 survey. The National
      TB Programme should prioritise the detection and treatment of MDR-TB to reduce
      transmission of MDR-TB in the community.

PMID- 25946356
TI  - Epidemiology of drug-resistant tuberculosis among children and adolescents in
      South Africa, 2005-2010.
AB  - OBJECTIVE: To describe the demographic and clinical characteristics of children
      and adolescents diagnosed with resistance to any anti-tuberculosis drug (drug
      resistant tuberculosis; DR-TB) in South Africa. DESIGN: We retrospectively
      reviewed medical records of all children (<13 years) and adolescents (13 to <18
      years) with DR-TB at specialty hospitals in four South African provinces from
      2005 to 2010. RESULTS: During the review period, 774 children and adolescents
      (median age 11.3 years) were diagnosed with DR-TB at selected facilities. A high
      proportion of patients had a history of previous TB treatment (285/631; 45.2%),
      human immunodeficiency virus (HIV) infection (375/685; 54.7%), contact with a TB
      case (347/454; 76.4%), and smear-positive (443/729; 60.8%), cavitary (253/680,
      38.7%) disease. Eighty-two per cent of patients with HIV infection received
      antiretroviral therapy. Of 626 patients diagnosed with multidrug-resistant TB
      (MDR-TB), 561 (89.6%) received a regimen consistent with national guidelines; the
      median length of treatment was 22 months (IQR 16-25). Among 400 patients with any
      DR-TB and a known outcome, 20.3% died during treatment. CONCLUSION: Pediatric DR
      TB in these provinces is characterized by complex clinical features at diagnosis,
      with one in five children dying during treatment. History of previous treatment
      and contact with a TB patient indicate opportunities for earlier diagnosis and
      treatment to improve outcomes.

PMID- 25946358
TI  - A comparison of the Xpert((r)) MTB/RIF and GenoType((r)) MTBDRplus assays in
      Georgia.
AB  - Few studies have directly compared the performance of rapid molecular diagnostic
      tests for tuberculosis (TB). We found that the commercially available molecular
      diagnostic tests Xpert((r)) MTB/RIF and GenoType((r)) MTBDRplus both provided
      timely and accurate results compared to conventional phenotypic tests in
      detecting TB and rifampicin resistance. 

PMID- 25946359
TI  - Pyrazinamide resistance in Mycobacterium tuberculosis arises after rifampicin and
      fluoroquinolone resistance.
AB  - BACKGROUND: Multidrug-resistant (MDR) and extensively drug-resistant (XDR)
      strains of Mycobacterium tuberculosis (TB) constitute a major public health
      concern. OBJECTIVE: To determine the timing of pncA mutations that confer
      pyrazinamide (PZA) resistance in relation to mutations conferring resistance to
      isoniazid (INH) and rifampicin (RMP). DESIGN: Isolates from two major urban
      centres--Paris (101 strains) and Shanghai (171 strains)--were investigated for
      the association of pncA mutations with resistance to drugs other than PZA.
      RESULTS: The proportion of pncA mutations found in INH-monoresistant strains was
      not increased. CONCLUSION: pncA mutations associated with PZA resistance were
      found almost exclusively in MDR-TB strains, underlining the importance of
      determining PZA resistance when treating MDR- or XDR-TB.

PMID- 25946361
TI  - Experience in implementing a quality management system in a tuberculosis
      laboratory, Kisumu, Kenya.
AB  - We implemented a quality management system (QMS) and documented our improvements
      in a tuberculosis (TB) laboratory in Kisumu, Kenya. After implementation of the
      QMS, a sustained reduction in culture contamination rates for solid (from 15.4%
      to 5.3%) and liquid media (from 15.2% to 9.3%) was observed, and waste from
      product expiry was reduced significantly. External quality assurance (EQA)
      results were satisfactory before and after QMS implementation, and a client
      survey after implementation revealed 98% satisfaction. The laboratory attained
      ISO 15189 accreditation in October 2013. The implementation of QMS facilitated
      the attainment of target quality indicators, reduced waste due to expiry and led
      to high client satisfaction. 

PMID- 25946360
TI  - Diabetes mellitus is associated with cavities, smear grade, and multidrug
      resistant tuberculosis in Georgia.
AB  - SETTING: National tuberculosis (TB) treatment facility in the country of Georgia.
      OBJECTIVE: To determine the prevalence of diabetes mellitus (DM) and pre-DM among
      patients with TB using glycosylated-hemoglobin (HbA1c), and to estimate the
      association between DM and clinical characteristics and response to anti
      tuberculosis treatment. DESIGN: A cohort study was conducted from 2011 to 2014 at
      the National Centre for TB and Lung Disease in Tbilisi. Patients aged ? 35 years
      with pulmonary TB were included. HbA1c was used to define DM (? 6.5%), pre-DM (?
      5.7-6.4%), and no DM (<5.7%). Interviews and medical chart abstraction were
      performed. Regression analyses estimated associations between DM and 1) baseline
      TB characteristics and 2) anti-tuberculosis treatment outcomes. RESULTS: A total
      of 318 newly diagnosed patients with TB were enrolled. The prevalence of DM and
      pre-DM was 11.6% and 16.4%, respectively. In multivariable analyses, patients
      with TB-DM had more cavitation (adjusted OR [aOR] 2.26), higher smear grade (aOR
      2.37), and more multidrug-resistant TB (MDR-TB) (aOR 2.27) than patients without
      DM. The risk of poor anti-tuberculosis treatment outcomes was similar among
      patients with and those without DM (28.1% vs. 23.6%). CONCLUSION: DM and pre-DM
      were common among adults with newly diagnosed pulmonary TB in Tbilisi, Georgia,
      and DM was associated with more clinical symptoms, and MDR-TB, at presentation.

PMID- 25946362
TI  - Cost-utility analysis of LED fluorescence microscopy in the diagnosis of
      pulmonary tuberculosis in Indian settings.
AB  - BACKGROUND: With support from the Stop TB Partnership's TB REACH Wave 2 Grant,
      diagnostic microscopy services for tuberculosis (TB) were upgraded from
      conventional Ziehl-Neelsen (ZN) based sputum microscopy to light emitting diode
      technology-based fluorescence microscopy (LED FM) in 200 high-workload microscopy
      centres in India as a pilot intervention. OBJECTIVE: To evaluate the cost
      effectiveness of LED-FM over conventional ZN microscopy to inform further scale
      up. METHODS: A decision-tree model was constructed to assess the cost utility of
      LED FM over ZN microscopy. The results were summarised using incremental cost
      effectiveness ratio (ICER); one-way and probabilistic sensitivity analyses were
      also conducted to address uncertainty within the model. Data were analysed from
      200 medical colleges in 2011 and 2012, before and after the introduction of LED
      microscopes. A full costing analysis was carried out from the perspective of a
      national TB programme. RESULTS: The ICER was calculated at US$14.64 per
      disability-adjusted life-year, with an 82% probability of being cost-effective at
      a willingness-to-pay threshold equivalent to Indian gross domestic product per
      capita. CONCLUSIONS: LED FM is a cost-effective intervention for detecting TB
      cases in India at high-workload medical college settings.

PMID- 25946363
TI  - Association between interleukin-27 polymorphisms and pulmonary tuberculosis.
AB  - OBJECTIVE: To investigate the effect of interleukin (IL) 27 -964A/G, 2095T/G,
      4603G/A and 4730T/C gene polymorphisms on the development of pulmonary
      tuberculosis (PTB), radiographic characteristics and severity. DESIGN:
      Differences in the allele and genotype distributions of the -964A/G, 2095T/G,
      4603G/A and 4730T/C polymorphisms between 224 PTB patients and 233 healthy
      controls, between patients with single- and multi-lobe involvement, and between
      patients with and without cavitation, were investigated. Serum IL-27
      concentration was measured using an enzyme-linked immunosorbent assay. RESULTS:
      There were no significant differences in the allele or genotype distributions
      between PTB patients and healthy controls. However, the -964A/A genotype was more
      prevalent in patients with single-lobe involvement than the -964A/G or -964G/G
      genotype in patients with multi-lobe involvement (50.0% vs. 31.3%, P = 0.01).
      There was no difference between patients with and without cavitation (P > 0.05).
      Serum median IL-27 concentration was significantly higher in patients with single
      lobe involvement than in those with multi-lobe involvement (P = 0.03) and in
      those with -964A/A genotypes than in those with -964A/G or -964G/G genotypes (P =
      0.02). CONCLUSIONS: In terms of serum IL-27 levels, the -964 A/A genotype may be
      associated with a protective role that prevents the intrapulmonary spread of PTB
      rather than its development.

PMID- 25946364
TI  - Cord formation in BACTEC(TM) medium aids rapid identification of Mycobacterium
      tuberculosis complex.
AB  - Mycobacterium tuberculosis complex (MTC) organisms form serpentine cords in fluid
      culture medium. Reporting of a presumptive identification of MTC based on cording
      allows rapid identification of patients with tuberculosis. A total of 612
      positive mycobacterial cultures from 316 patients over 3 years (2008-2010) were
      evaluated for the presence of cord formation. Cording was identified in 426
      (69.6%) specimens, while the reference laboratory confirmed M. tuberculosis in
      424 specimens (69.3%). Sensitivity of the test in our laboratory was 99.1% (95%CI
      97.4-99.7) and specificity was 96.8% (95%CI 92.8-98.7). Presumptive
      identification of M. tuberculosis by the presence of cording formation is both
      sensitive and specific. 

PMID- 25946365
TI  - Antimicrobial activity of recombinant mature bovine neutrophil beta-defensin 4 on
      mycobacterial infection.
AB  - BACKGROUND: Previous studies have shown that human cathelicidin and defensins
      have effective antimicrobial activity against Mycobacterium spp. OBJECTIVE: To
      investigate the antimycobacterial effect of mature bovine neutrophil beta
      defensin (mBNBD) 4 against Mycobacterium spp. infection for the first time.
      DESIGN: mBNBD4 protein was expressed in Pichia pastoris GS115. We used
      immunofluorescent assay to detect whether the recombinant mBNBD4 had entered the
      macrophages. The antimycobacterial activity of mBNBD4 was tested through colony
      forming unit (cfu) assay. Morphological changes in the cell wall of M. bovis
      treated with mBNBD4 were observed by scanning electron microscope. RESULTS:
      mBNBD4 was expressed and successfully purified from P. pastoris with intact
      antimicrobial activity. The recombinant protein was able to enter Raw 264.7
      macrophages and exhibited potent in vitro bactericidal activity against M.
      smegmatis and M. bovis. The cell wall of M. bovis was disrupted after interaction
      with mBNBD4. Exogenous addition of mBNBD4 to both Raw 264.7 and THP-1 derived
      macrophages reduced the intracellular survival of M. bovis and M. tuberculosis
      relative to control cells. CONCLUSION: Our data show that mBNBD4 plays an
      important role in inhibiting mycobacterial growth and in controlling
      intracellular survival of mycobacteria. mBNBD4 could therefore an effective
      antimycobacterial molecule in combination with other measures.

PMID- 25946366
TI  - The 100 top-cited tuberculosis research studies.
AB  - The examination of top-cited studies is a useful method for identify and
      monitoring outstanding scientific research. The objective of this study was to
      identify and analyse the characteristics of the top 100 cited research studies on
      tuberculosis (TB) based on the Web of Knowledge. Overall, the top 100 cited
      studies were cited between 366 and 4443 times, and were published between 1995
      and 2010, with the largest number of publications in 2003 and in 1995. Four
      studies were attributed to a single author and 10 to two authors; the number of
      authors exceeded six in 50 studies. Nine authors had more than one study as the
      first author and 18 authors had more than one study as the corresponding author.
      The United States contributed the largest number of studies, followed by the
      United Kingdom and France. The institutions with the largest number of articles
      were the Institut National de la Sante et de la Recherche Medicale in France and
      the University of California in the United States. The studies appeared in 35
      journals, with 11 published in Science, followed by PNAS and NEJM. The majority
      of TB articles have been published in those medical journals with the highest
      impact factors, and are from the most industrialised countries. 

PMID- 25946367
TI  - Association of extra-pulmonary tuberculosis with age, sex and season differs
      depending on the affected organ.
AB  - SETTING: Data from tuberculosis (TB) cases in Germany who are continuously
      monitored for the purposes of epidemiological surveillance and disease control.
      OBJECTIVE: To examine the distribution of age, sex, place of birth, seasonality
      and recurrence of TB disease in different types of TB organ manifestations, with
      particular focus on lymph nodes and pleura. DESIGN: All TB cases reported to the
      Berlin State Office for Health and Social Affairs (LAGeSo) in Berlin, Germany,
      between 2001 and 2012 were analysed. RESULTS: Significant differences with regard
      to seasonal variation as well as age and sex distribution were seen when
      comparing pleural TB and TB of the extrathoracic lymph nodes, the predominant
      types of extra-pulmonary TB. EPTB was generally more prevalent in patients born
      outside Europe. In contrast to a previous study, an increase in recurrent TB was
      not observed in EPTB when compared to pulmonary TB cases. CONCLUSION: Significant
      differences in TB organ manifestation in association with season, sex and age
      suggest different pathophysiological mechanisms of disease development. Future
      studies might provide further insight into the mechanism of TB development and
      may therefore be of help in the prevention and treatment of EPTB.

PMID- 25946368
TI  - Relationship between serum vitamin D concentrations and clinical outcome of
      community-acquired pneumonia.
AB  - SETTING: Hospitalised patients with community-acquired pneumonia (CAP) in a
      tertiary referral hospital in South Korea. OBJECTIVE: To determine the burden of
      vitamin D deficiency in patients hospitalised with CAP and to investigate whether
      vitamin D deficiency affected clinical outcomes. DESIGN: Serum 25-hydroxyvitamin
      D (25[OH]D) levels were measured at admission; vitamin D deficiency was defined
      as 25(OH)D <20 ng/ml. Data were retrospectively analysed for incidence of vitamin
      D deficiency. The primary outcome was the relationship between serum vitamin D
      concentration and 28-day all-cause mortality in CAP. RESULTS: The mean age was
      68.1 years (standard deviation [SD] +/- 14.6), and the mean pneumonia severity
      index was 98.0 (+/- SD 28.6). Of the 797 patients (males 66.0%), 641 (80.4%) had
      vitamin D deficiency. Overall mean serum 25(OH)D level was 14.0 +/- 7.4 ng/ml.
      The 28-day all-cause mortality rate in vitamin D-deficient patients was
      significantly higher than in non-deficient patients (8.3% vs. 2.6%, P = 0.01),
      and serum vitamin D level was negatively associated with risk of 28-day mortality
      in CAP after adjustment for pneumonia severity index and serum lactate levels (OR
      0.94, 95%CI 0.90-0.99, P < 0.01). CONCLUSION: The prevalence of vitamin D
      deficiency was ~80% in patients hospitalised with CAP. Vitamin D deficiency was
      also a significant predictor of increased 28-day all-cause mortality.

PMID- 25946369
TI  - Coverage of and factors associated with pneumococcal vaccination in chronic
      obstructive pulmonary disease.
AB  - SETTING: Patients aged ? 40 years with a diagnosis of chronic obstructive
      pulmonary disease (COPD; codes R95, R79 and R91 in the International
      Classification for Primary Care) registered in primary care clinical records in
      the Autonomous Community of Madrid, Spain. OBJECTIVE: To assess pneumococcal
      vaccination coverage in patients with COPD and to analyse factors associated with
      vaccination uptake. DESIGN: Population-based cross-sectional study in which data
      were collected in September 2010. RESULTS: We found that 93,797 patients (72.0%
      men and 28.0% women) had COPD. Overall coverage was 65.5% (67.5% men vs. 60.4%
      women, P < 0.001). In patients aged 40-59 years, coverage was 19.5%, reaching
      75.8% in those aged ? 60 years. In patients aged <60 years, uptake was associated
      with a higher number of comorbidities and appropriate adherence to seasonal
      influenza and pandemic vaccination schedules. In patients aged ? 60 years,
      factors associated with uptake in both sexes were older age and appropriate
      adherence to seasonal influenza vaccination schedules. Factors associated with
      uptake in men were concomitant comorbidities and pandemic vaccination.
      CONCLUSION: Vaccination coverage in individuals aged <60 years with COPD is less
      than acceptable in Madrid. Coverage was higher in men and in patients with
      another chronic condition.

PMID- 25946370
TI  - Incidence of idiopathic pulmonary fibrosis in Korea based on the 2011
      ATS/ERS/JRS/ALAT statement.
AB  - OBJECTIVE: To estimate the annual incidence rate of interstitial lung disease
      (ILD) and idiopathic pulmonary fibrosis (IPF) in Korea. DESIGN: A retrospective
      cohort design using the Korean Health Insurance Review and Assessment Service
      (HIRA) database spanned the period from January 2008 to December 2012. Patients
      with ILD and IPF were identified based on the International Classification of
      Disease-10 (ICD-10) diagnosis and procedure codes. Definition 1 is code J84
      (ILD); Definition 2 is code J84 plus high-resolution computed tomography (HRCT),
      bronchoalveolar lavage (BAL) or lung biopsy; Definition 3 is code J84.1 (ILD with
      fibrosis); Definition 4 is code J84.1 and HRCT, BAL or lung biopsy; and
      Definition 5 is code J84.1A (IPF), and was specifically implemented for IPF.
      RESULTS: The incidence rates of ILD per 100,000 population based on Definitions 1
      5 were respectively 48.5, 32.2, 16.2, 11.4 and 1.7. CONCLUSION: The incidence of
      ILD with fibrosis was approximately 23% of overall ILD incidence. IPF incidence
      was approximately 10% of the incidence of ILD with fibrosis. Based on the new
      ATS/ERS/JRS/ALAT statement published in 2011, the incidence rate of IPF was
      1.7/100,000.

PMID- 25946371
TI  - Percutaneous treatment for pulmonary hypertension caused by pulmonary artery
      stenosis due to anthracosis.

PMID- 25946372
TI  - Increased long-latency reflex activity as a sufficient explanation for childhood
      hypertonic dystonia: a neuromorphic emulation study.
AB  - OBJECTIVE: Childhood dystonia is a movement disorder that interferes with daily
      movements and can have a devastating effect on quality of life for children and
      their families. Although injury to basal ganglia is associated with dystonia, the
      neurophysiological mechanisms leading to the clinical manifestations of dystonia
      are not understood. Previous work suggested that long-latency stretch reflex
      (LLSR) is hyperactive in children with hypertonia due to secondary dystonia. We
      hypothesize that abnormal activity in motor cortices may cause an increase in the
      LLSR leading to hypertonia. APPROACH: We modeled two possibilities of hyperactive
      LLSR by either creating a tonic involuntary drive to cortex, or increasing the
      synaptic gain in cortical neurons. Both models are emulated using programmable
      very-large-scale-integrated-circuit hardware to test their sufficiency for
      producing dystonic symptoms. The emulation includes a joint with two Hill-type
      muscles, realistic muscle spindles, and 2,304 Izhikevich-type spiking neurons.
      The muscles are regulated by a monosynaptic spinal pathway with 32 ms delay and a
      long-latency pathway with 64 ms loop-delay representing transcortical/supra
      spinal connections. MAIN RESULTS: When the limb is passively stretched, both
      models produce involuntary resistance with increased antagonist EMG responses
      similar to human data; also the muscle relaxation is delayed similar to human
      data. Both models predict reduced range of motion in voluntary movements.
      SIGNIFICANCE: Although our model is a highly simplified and limited
      representation of reflex pathways, it shows that increased activity of the LLSR
      is by itself sufficient to cause many of the features of hypertonic dystonia.

PMID- 25946373
TI  - Nodular Amyloidosis of the Penis: A Case Demonstrating Keratinocyte Origin.

PMID- 25946374
TI  - Indication of Complete Spin Filtering in Atomic-Scale Nickel Oxide.
AB  - Generating highly spin-polarized currents at the nanoscale is essential for spin
      current manipulations and spintronic applications. We find indications for up to
      100% spin-polarized currents across nickel oxide atomic junctions formed between
      two nickel electrodes. The degree of spin polarization is probed by analyzing the
      shot noise resulting from the discrete statistics of spin-polarized electron
      transport. We show that spin filtering can be significantly enhanced by local
      chemical modifications at the single-atom level. This approach paves the way for
      effective manipulations of spin transport at the fundamental limit of
      miniaturization. 

PMID- 25946376
TI  - Randomized trial to increase colorectal cancer screening in an ethnically diverse
      sample of first-degree relatives.
AB  - BACKGROUND: Ethnic minorities, especially African Americans and Latinos, bear a
      disproportionate burden of colorectal cancer (CRC), as reflected in incidence,
      cancer stage, and mortality statistics. In all ethnic groups, first-degree
      relatives (FDRs) of CRC cases are at an elevated disease risk. However, underuse
      of CRC screening persists and is particularly evident among minority groups. The
      current study tested a stepped intervention to increase CRC screening among an
      ethnically diverse sample of FDRs of CRC cases. METHODS: A statewide cancer
      registry was used to recruit CRC cases and through them their FDRs. Relatives who
      were not current on CRC screening were randomized to intervention or usual-care
      control arms. The stepped intervention consisted of ethnically targeted and
      individually tailored print materials followed by telephone counseling for those
      unscreened at 6 months. RESULTS: The study sample of 1280 individuals consisted
      of 403 Latino, 284 African American, 242 Asian, and 351 white FDRs. Statistically
      significant effects were observed for the cumulative print plus telephone
      intervention at 12 months (26% in the intervention vs 18% in the control group)
      and the print intervention alone at 6 months (15% in the intervention vs 10% in
      the control group). The effect of the print intervention alone versus the
      cumulative interventions was not statistically significantly different.
      Stratified analyses indicated that the intervention was effective among white,
      Latino, and Asian individuals, but not among African-Americans. CONCLUSIONS:
      Overall, the intervention was effective in increasing screening rates.
      Oversampling racial/ethnic minorities allowed for the examination of effects
      within subgroups, revealing no effect among African American individuals. This
      finding illustrates the importance of including sufficient numbers of
      participants from diverse ethnic subgroups in intervention research to enable
      such stratified analyses.

PMID- 25946375
TI  - p27(Kip1) participates in the regulation of endoreplication in differentiating
      chick retinal ganglion cells.
AB  - Nuclear DNA duplication in the absence of cell division (i.e. endoreplication)
      leads to somatic polyploidy in eukaryotic cells. In contrast to some invertebrate
      neurons, whose nuclei may contain up to 200,000-fold the normal haploid DNA
      amount (C), polyploid neurons in higher vertebrates show only 4C DNA content. To
      explore the mechanism that prevents extra rounds of DNA synthesis in these latter
      cells we focused on the chick retina, where a population of tetraploid retinal
      ganglion cells (RGCs) has been described. We show that differentiating chick RGCs
      that express the neurotrophic receptors p75 and TrkB while lacking retinoblastoma
      protein, a feature of tetraploid RGCs, also express p27(Kip1). Two different
      short hairpin RNAs (shRNA) that significantly downregulate p27(Kip1) expression
      facilitated DNA synthesis and increased ploidy in isolated chick RGCs. Moreover,
      this forced DNA synthesis could not be prevented by Cdk4/6 inhibition, thus
      suggesting that it is triggered by a mechanism similar to endoreplication. In
      contrast, p27(Kip1) deficiency in mouse RGCs does not lead to increased ploidy
      despite previous observations have shown ectopic DNA synthesis in RGCs from
      p27(Kip1-/-) mice. This suggests that a differential mechanism is used for the
      regulation of neuronal endoreplication in mammalian versus avian RGCs. 

PMID- 25946378
TI  - Does Rescue Collapse Mandate a Paradigm Shift in the Field Management of
      Avalanche Victims?

PMID- 25946377
TI  - International ring trial for the validation of an event-specific Golden Rice 2
      quantitative real-time polymerase chain reaction method.
AB  - This article describes the international validation of the quantitative real-time
      polymerase chain reaction (PCR) detection method for Golden Rice 2. The method
      consists of a taxon-specific assay amplifying a fragment of rice Phospholipase D
      alpha2 gene, and an event-specific assay designed on the 3' junction between
      transgenic insert and plant DNA. We validated the two assays independently, with
      absolute quantification, and in combination, with relative quantification, on DNA
      samples prepared in haploid genome equivalents. We assessed trueness, precision,
      efficiency, and linearity of the two assays, and the results demonstrate that
      both the assays independently assessed and the entire method fulfill European and
      international requirements for methods for genetically modified organism (GMO)
      testing, within the dynamic range tested. The homogeneity of the results of the
      collaborative trial between Europe and Asia is a good indicator of the robustness
      of the method. 

PMID- 25946379
TI  - Evaluation of the Results of Using Toric IOL in the Cataract Surgery of
      Keratoconus Patients.
AB  - PURPOSE: To evaluate the results of using AcrySof toric intraocular lenses (IOLs)
      in the cataract surgery of patients with keratoconus (KCN). METHODS: In this
      study, 23 eyes of 17 patients with KCN who underwent cataract surgery using the
      toric IOL were evaluated. The amount and axis of the corneal astigmatism were
      measured by manual keratometry, corneal topography, refractive map of the
      Pentacam, and equivalent K reading of the Pentacam in all patients. RESULTS: The
      mean uncorrected visual acuity increased significantly 3 months after the surgery
      (P<0.01). The mean best-corrected visual acuity was 0.28+/-0.10 logMAR, 0.51+/
      0.52 logMAR, and 0.83+/-0.55 logMAR before the surgery and 0.16+/-0.09 logMAR,
      0.18+/-0.12 logMAR, and 0.35+/-0.13 logMAR after the surgery in the mild,
      moderate, and severe KCN groups, respectively (P<0.01). The mean IOL rotation was
      2.50+/-1.18 degrees, 2.50+/-1.51 degrees, and 2.67+/-1.15 degrees in the mild,
      moderate, and severe KCN groups. The lowest mean absolute error was seen in the
      mild and moderate KCN groups with corneal topography-derived keratometry using
      the SRK/T formula and in the severe KCN group with corneal topography-derived
      keratometry and manual keratometry using the SRK/T and SRK II formulas.
      CONCLUSIONS: The use of toric IOLs resulted in desirable vision and refraction in
      the cataract surgery of patients with nonprogressive KCN. As for determining the
      IOL power, it seems that keratometry derived from the 3 mm central zone in the
      axial map of corneal topography using the SRK/T formula has the lowest error.

PMID- 25946380
TI  - All-trans retinoic acid suppresses topoisomerase IIalpha through the proteasomal
      pathway.
AB  - Topoisomerase IIalpha is a nuclear enzyme that alters DNA topology. It is a well
      known anticancer target and related to cell differentiation status. All-trans
      retinoic acid (ATRA), an important active metabolite of vitamin A, is a promising
      anticancer agent in numerous malignancies. However, there are little data on the
      effect of retinoids on topoisomerase IIalpha regulation. In the present study, we
      investigated the relationship between ATRA and topoisomerase IIalpha, and the
      potential mechanisms of ATRA on topoisomerase IIalpha regulation. In several
      human carcinoma cell lines, ATRA was shown to suppress topoisomerase IIalpha
      protein, but not mRNA expression. ATRA induced the degradation of topoisomerase
      IIalpha through the proteasome pathway, but not the lysosome pathway.
      Ubiquitination was involved in this degradation. Western blot and
      immunocytochemistry proved that ATRA-induced topoisomerase IIalpha repression
      occurred only in the cell nuclei. ATRA not only influenced the cycle procession
      but also reduced the expression of cyclin D1. Cyclin D1, which is involved in
      cell differentiation, was regulated by topoisomerase IIalpha. Similar to cyclin
      D1, knockdown of topoisomerase IIalpha resulted in the increased differentiation
      of the cells, which was in contrast to the overexpression of topoisomerase
      IIalpha in the cells. Taken together, these data suggested that ATRA could target
      topoisomerase IIalpha and exert potential beneficial effects on cell
      differentiation. 

PMID- 25946382
TI  - Chapter 2 traumatic brain injury research in military populations.
AB  - Traumatic brain injury (TBI) in all of its forms--blast, concussive, and
      penetrating--has been an unfortunate sequela of warfare since ancient times. The
      continued evolution of military munitions and armor on the battlefield, as well
      as the insurgent use of improvised explosive devices, has led to blast-related
      TBI whose long-term effects on behavior and cognition are not yet known. Advances
      in medical care have greatly increased survival from these types of injuries.
      Therefore, an understanding of the potential health effects of TBI is essential.
      This review focuses on specific aspects of military-related TBI. There exists a
      large body of literature reporting the environmental conditions, forces, and
      staging of injury. Many of these studies are focused on the neuropathology of
      TBI, due to blast overpressure waves, and the emergence of large numbers of mild
      blast-related TBI cases.

PMID- 25946381
TI  - Chapter 1 Common Data Elements and Federal Interagency Traumatic Brain Injury
      Research Informatics System for TBI Research.
AB  - Despite increased attention to traumatic brain injury (TBI), there remains no
      specific treatment and available interventions focus rather on the prevention of
      secondary injury. One of the reasons posited for the lack of a successful therapy
      is the amalgamation of various types of injuries under the same severity category
      in clinical trials. Informatics approaches have been suggested as a means to
      develop an improved classification system for TBI. As a result of federal
      interagency efforts, common data elements (CDEs) for TBI have now been developed.
      Further, the Federal Interagency Traumatic Brain Injury Research Informatics
      System (FITBIR) has been created and is now available for TBI researchers to both
      add and retrieve data. This chapter will discuss the goals, development, and
      evolution of the CDEs and FITBIR and discuss how these tools can be used to
      support TBI research. A specific exemplar using the CDEs and lessons learned from
      working with the CDEs and FITBIR are included to aid future researchers. 

PMID- 25946383
TI  - Chapter 3 animal models of traumatic brain injury: is there an optimal model that
      parallels human brain injury?
AB  - Traumatic brain injury (TBI) is the leading cause of mortality and morbidity in
      the younger population worldwide. Survivors of TBI often experience long-term
      disability in the form of cognitive, sensorimotor, and affective impairments.
      Despite the high prevalence in, and cost of TBI to, both individuals and society,
      some of its underlying pathophysiology is not completely understood. Animal
      models have been developed over the past few decades to closely replicate the
      different facets of TBI in humans to better understand the underlying
      pathophysiology and behavioral impairments and assess potential therapies that
      can promote neuroprotection. However, no effective treatment for TBI has been
      established to date in the clinical setting, despite promising results generated
      in preclinical studies in the use of neuroprotective strategies. The failure to
      translate results from preclinical studies to the clinical setting underscores a
      compelling need to revisit the current state of knowledge in the use of animal
      models in TBI. 

PMID- 25946384
TI  - Chapter 4 genomics, transcriptomics, and epigenomics in traumatic brain injury
      research.
AB  - The long-term effects and significant impact of the full spectrum of traumatic
      brain injury (TBI) has received increased attention in recent years. Despite
      increased research efforts, there has been little movement toward improving
      outcomes for the survivors of TBI. TBI is a heterogeneous condition with a
      complex biological response, and significant variability in human recovery
      contributes to the difficulty in identifying therapeutics that improve outcomes.
      Personalized medicine, identifying the best course of treatment for a given
      individual based on individual characteristics, has great potential to improve
      recovery for TBI survivors. The advances in medical genetics and genomics over
      the past 20 years have increased our understanding of many biological processes.
      A substantial amount of research has focused on the genomic, transcriptomic, and
      epigenomic profiles in many health and disease states, including recovery from
      TBI. The focus of this review chapter is to describe the current state of the
      science in genomic, transcriptomic, and epigenomic research in the TBI
      population. There have been some advancements toward understanding the genomic,
      transcriptomic, and epigenomic processes in humans, but much of this work remains
      at the preclinical stage. This current evidence does improve our understanding of
      TBI recovery, but also serves as an excellent platform upon which to build
      further study toward improved outcomes for this population. 

PMID- 25946385
TI  - Chapter 5 cerebral perfusion pressure and intracranial pressure in traumatic
      brain injury.
AB  - Nearly 300,000 children and adults are hospitalized annually with traumatic brain
      injury (TBI) and monitored for many vital signs, including intracranial pressure
      (ICP) and cerebral perfusion pressure (CPP). Nurses use these monitored values to
      infer the risk of secondary brain injury. The purpose of this chapter is to
      review nursing research on the monitoring of ICP and CPP in TBI. In this context,
      nursing research is defined as the research conducted by nurse investigators or
      research about the variables ICP and CPP that pertains to the nursing care of the
      TBI patient, adult or child. A modified systematic review of the literature
      indicated that, except for sharp head rotation and prone positioning, there are
      no body positions or nursing activities that uniformly or nearly uniformly result
      in clinically relevant ICP increase or decrease. In the smaller number of studies
      in which CPP is also measured, there are few changes in CPP since arterial blood
      pressure generally increases along with ICP. Considerable individual variation
      occurs in controlled studies, suggesting that clinicians need to pay close
      attention to the cerebrodynamic responses of each patient to any care maneuver.
      We recommend that future research regarding nursing care and ICP/CPP in TBI
      patients needs to have a more integrated approach, examining comprehensive care
      in relation to short- and long-term outcomes and incorporating multimodality
      monitoring. Intervention trials of care aspects within nursing control, such as
      the reduction of environmental noise, early mobilization, and reduction of
      complications of immobility, are all sorely needed. 

PMID- 25946387
TI  - Chapter 7 the relationship between coping and psychological adjustment in family
      caregivers of individuals with traumatic brain injury: a systematic review.
AB  - A systematic review was conducted to evaluate the association between coping (as
      measured by the Ways of Coping Questionnaire [WOCQ]) and psychological adjustment
      in caregivers of individuals with traumatic brain injury (TBI). A search
      conducted using the CINAHL, Medline, and PsycINFO databases yielded 201 citations
      between 1974 and 2014. A total of seven articles met the inclusion criteria;
      namely, the respondents who completed the WOCQ were family caregivers of
      individuals with TBI (including 66-item, 42-item, or 21-item versions). Reviews
      were conducted in accordance with the American Academy of Neurology guidelines
      (2011) for classifying evidence. The results found no Class 1 or Class II studies
      but only four Class III and three Class IV studies. The major finding across the
      better-rated Class III studies was that the use of emotion-focused coping and
      problem-focused coping was possibly associated with psychological adjustment in
      caregivers. The Class IV studies were determined to be inadequate or conflicting
      in determining the association between coping and psychological adjustment.
      Future studies need to employ carefully crafted designs, adhere to statistical
      procedure, apply advanced analytic techniques, and employ explicit models of
      coping, which will increase the accuracy and generalizability of the findings. 

PMID- 25946386
TI  - Chapter 6 state of the science of pediatric traumatic brain injury: biomarkers
      and gene association studies.
AB  - OBJECTIVES: Our objective is to review the most widely used biomarkers and gene
      studies reported in pediatric traumatic brain injury (TBI) literature, to
      describe their findings, and to discuss the discoveries and gaps that advance the
      understanding of brain injury and its associated outcomes. Ultimately, we aim to
      inform the science for future research priorities. DATA SOURCES: We searched
      PubMed, MEDLINE, CINAHL, and the Cochrane Database of Systematic Reviews for
      published English language studies conducted in the last 10 years to identify
      reviews and completed studies of biomarkers and gene associations in pediatric
      TBI. Of the 131 biomarker articles, only 16 were specific to pediatric TBI
      patients, whereas of the gene association studies in children with TBI, only four
      were included in this review. CONCLUSION: Biomarker and gene attributes are
      grossly understudied in pediatric TBI in comparison to adults. Although recent
      advances recognize the importance of biomarkers in the study of brain injury, the
      limited number of studies and genomic associations in the injured brain has shown
      the need for common data elements, larger sample sizes, heterogeneity, and common
      collection methods that allow for greater understanding of the injured pediatric
      brain. By building on to the consortium of interprofessional scientists,
      continued research priorities would lead to improved outcome prediction and
      treatment strategies for children who experience a TBI. IMPLICATIONS FOR NURSING
      RESEARCH: Understanding recent advances in biomarker and genomic studies in
      pediatric TBI is important because these advances may guide future research,
      collaborations, and interventions. It is also important to ensure that nursing is
      a part of this evolving science to promote improved outcomes in children with
      TBIs.

PMID- 25946388
TI  - Chapter 8 Military Personnel With Traumatic Brain Injuries and Insomnia Have
      Reductions in PTSD and Improved Perceived Health Following Sleep Restoration: A
      Relationship Moderated by Inflammation.
AB  - BACKGROUND: Up to one-third of deployed military personnel sustain a traumatic
      brain injury (TBI). TBIs and the stress of deployment contribute to the
      vulnerability for chronic sleep disturbance, resulting in high rates of insomnia
      diagnoses as well as symptoms of posttraumatic stress disorder (PTSD),
      depression, and declines in health-related quality of life (HRQOL). Inflammation
      is associated with insomnia; however, the impact of sleep changes on comorbid
      symptoms and inflammation in this population is unknown. METHODS: In this study,
      we examined the relationship between reported sleep changes and the provision of
      the standard of care, which could include one or more of the following: cognitive
      behavioral therapy (CBT), medications, and continuous positive airway pressure
      (CPAP). We compared the following: (a) the group with a decrease in the
      Pittsburgh Sleep Quality Index (PSQI; restorative sleep) and (b) the group with
      no change or increase in PSQI (no change). Independent t tests and chi-square
      tests were used to compare the groups on demographic and clinical
      characteristics, and mixed between-within subjects analysis of variance tests
      were used to determine the effect of group differences on changes in comorbid
      symptoms. Linear regression models were used to examine the role of inflammation
      in changes in symptoms and HRQOL. RESULTS: The sample included 70 recently
      deployed military personnel with TBI, seeking care for sleep disturbances. Thirty
      seven participants reported restorative sleep and 33 reported no sleep changes or
      worse sleep. The two groups did not differ in demographic characteristics or
      clinical symptoms at baseline. The TBI+restored sleep group had significant
      reductions in PTSD and depression over the 3-month period, whereas the TBI+no
      change group had a slight increase in both PTSD and depression. The TBI+restored
      sleep group also had significant changes in HRQOL, including the following HRQOL
      subcomponents: physical functioning, role limitations in physical health, social
      functioning, emotional well-being, energy/fatigue, and general health
      perceptions. In a linear regression model using a forced entry method, the
      dependent variable of change in C-reactive protein (CRP) concentrations was
      significantly related to changes in PTSD symptoms and HRQOL in the TBI+restored
      sleep group, with R2=0.43, F33,3=8.31, p<.01. CONCLUSIONS: Military personnel
      with TBIs who have a reduction in insomnia symptoms following a standard-of-care
      treatment report less severe symptoms of depression and PTSD and improved HRQOL,
      which relate to decreased plasma concentrations of CRP. These findings suggest
      that treatment for sleep disturbances in this TBI+military population is
      associated with improvements in health and decreases in inflammation. The
      contributions of inflammation-induced changes in PTSD and depression in sleep
      disturbances in TBI + military personnel require further study.

PMID- 25946391
TI  - Hemostatic glues in tonsillectomy: A systematic review.
AB  - OBJECTIVES/HYPOTHESIS: The aim of this study was to compare use of hemostatic
      glues to conventional techniques of intraoperative hemostasis for tonsillectomy.
      STUDY DESIGN: A systematic review of the literature and meta-analysis. METHODS:
      All published prospective controlled trials that compared hemostatic glues to
      conventional techniques of hemostasis were identified. We performed a meta
      analysis of articles comparing fibrin sealant to electrocautery, and of those
      comparing electrocautery to electrocautery plus fibrin hemostasis. RESULTS: Seven
      studies were identified that made qualifications for review, with a total of 748
      patients. Outcome measures were postoperative hemorrhage recorded by
      investigators, and visual analogue scores of pain for day 1, day 3, and day 10
      postoperatively. Use of fibrin sealant was not associated with a reduction in
      hemorrhage rates following tonsillectomy when compared to electrocautery (pooled
      relative risk [RR] 0.315; 95% confidence intervals [CI]: 0.047-2.093, 224
      patients). No statistical difference in bleeding rate was seen between
      electrocautery hemostasis alone, compared to electrocautery with fibrin sealant
      (pooled RR 1.742; 95% CI: 0.433-7.005, 108 patients). No statistically
      significant difference in pain was identified. CONCLUSIONS: Pain and bleeding are
      significant causes of morbidity post-tonsillectomy. We conclude that there is no
      significant evidence to support hemostatic glues over current techniques for
      reducing severity of these outcomes. Consequently, we do not recommended
      hemostatic glues for routine use in current clinical practice. Studies were
      generally of low quality and inadequately powered to detect a statistical
      difference, even when pooled. We advocate further research to facilitate future
      meta-analysis.

PMID- 25946390
TI  - From Skeletal Development to Tissue Engineering: Lessons from the Micromass
      Assay.
AB  - Damage and degeneration of the skeletal elements due to disease, trauma, and
      aging lead to a significant health and economical burden. To reduce this burden,
      skeletal tissue engineering strategies aim to regenerate functional bone and
      cartilage in the adult body. However, challenges still exist. Such challenges
      involve the identification of the external cues that determine differentiation,
      how to control chondrocyte hypertrophy, and how to achieve specific tissue
      patterns and boundaries. To address these issues, it could be insightful to look
      at skeletal development, a robust morphogenetic process that takes place during
      embryonic development and is commonly modeled in vitro by the micromass assay. In
      this review, we investigate what the tissue engineering field can learn from this
      assay. By comparing embryonic skeletal precursor cells from different anatomic
      locations and developmental stages in micromass, the external cues that guide
      lineage commitment can be identified. The signaling pathways regulating
      chondrocyte hypertrophy, and the cues required for tissue patterning, can be
      elucidated by combining the micromass assay with genetic, molecular, and
      engineering tools. The lessons from the micromass assay are limited by two major
      differences between developmental and regenerative skeletogenesis: cell type and
      scale. We highlight an important difference between embryonic and adult skeletal
      progenitor cells, in that adult progenitors are not able to form mesenchymal
      condensations spontaneously. Also, the mechanisms of tissue patterning need to be
      adjusted to the larger tissue engineering constructs. In conclusion, mechanistic
      insights of skeletal tissue generation gained from the micromass model could lead
      to improved tissue engineering strategies and constructs. 

PMID- 25946392
TI  - MRI-guided percutaneous transpedicular biopsy of thoracic and lumbar spine using
      a 0.23t scanner with optical instrument tracking.
AB  - PURPOSE: To prospectively evaluate the safety and accuracy of magnetic resonance
      imaging (MRI)-guided percutaneous transpedicular biopsy of thoracic and lumbar
      spine using 0.23T magnetic resonance imaging with optical tracking. MATERIALS AND
      METHODS: Sixty-seven thoracic and lumbar spine lesions in 67 patients underwent
      MRI-guided percutaneous transpedicular biopsy using 0.23T MRI with optical
      tracking. These lesions were divided into two groups according to the location:
      16 lesions in the thoracic spine and 51 lesions in the lumbar spine. The
      diagnostic accuracy, sensitivity, and specificity were calculated, and comparison
      of the two groups was performed using Fisher's exact test. Each patient was
      monitored for complications. RESULTS: All specimens obtained were sufficient for
      diagnosis. Histological examination of MRI-guided percutaneous biopsy revealed 38
      malignant and 29 benign lesions. The final diagnoses from surgery or clinical
      follow-up were 42 malignant lesions and 25 benign lesions. The combined
      diagnostic performance of MRI-guided percutaneous transpedicular thoracic and
      lumbar biopsy in diagnosing malignant tumors was as follows: accuracy, 94%;
      sensitivity, 89%; and specificity, 100%. There was no significant difference
      between the two groups (P = 1, Fisher's exact test). No serious complications
      occurred. CONCLUSION: MRI-guided percutaneous transpedicular biopsy is a safe and
      accurate diagnostic technique to evaluate thoracic and lumbar spine lesions.

PMID- 25946393
TI  - Using Theory to Identify Beliefs Associated with Intentions to Follow Fish
      Consumption Advisories Among Anglers Living in the Great Lakes Region.
AB  - Fish consumption advisories are issued by states, tribes, and federal agencies to
      provide guidance to consumers about eating sport-caught fish potentially affected
      by chemical contaminants. Previous work has found that while anglers report being
      aware that advisories are available, awareness and use of specific advisory
      recommendations is low. This study uses the Integrative Model of Behavioral
      Prediction (IMBP) to identify beliefs with potential to increase intentions to
      follow fish consumption advisories in Great Lakes states. We conducted a mail
      survey of 1,712 licensed anglers in seven of eight Great Lakes states (excluding
      Ohio) to gauge advisory awareness, cognitive factors influencing fish consumption
      behaviors (informed by the IMBP), and sociodemographic characteristics. Results
      show that most anglers reported being generally or vaguely aware of fish
      consumption advisories and try to follow them, but far fewer report being aware
      of specific advice needed to decide whether or not to consume different types of
      sport-caught fish. Informed by the IMBP, we also identify several behavioral,
      normative, and control beliefs that have sufficient room to change, strong
      associations with intentions to follow the advisories, and potential to be
      modified if targeted with strategic risk messages. Targeting these beliefs with
      strategic communication holds potential to increase the proportion of anglers
      intending to follow fish consumption advisory recommendations in choosing which
      fish to eat. 

PMID- 25946395
TI  - Water-plasma-assisted synthesis of black titania spheres with efficient visible
      light photocatalytic activity.
AB  - Black titania spheres (H-TiO2-x) were synthesized via a simple green method
      assisted by water plasma at a low temperature and atmospheric pressure. The in
      situ production of highly energetic hydroxyl and hydrogen species from water
      plasma are the prominent factors in the oxidation and hydrogenation reactions
      during the formation of H-TiO2-x, respectively. The visible-light photocatalytic
      activity toward the dye degradation of H-TiO2-x can be attributed to the
      synergistic effect of large-surface area, visible-light absorption and the
      existence of oxygen vacancies and Ti(3+) sites. 

PMID- 25946394
TI  - Implications of intraglandular lymph node metastases in primary carcinomas of the
      parotid gland.
AB  - OBJECTIVES/HYPOTHESIS: Assess the diagnostic and prognostic relevance of
      intraglandular lymph node (IGLN) metastases in primary parotid gland carcinomas
      (PGCs). STUDY DESIGN: Retrospective study at a tertiary referral university
      hospital. METHODS: We reviewed the records of 95 patients with primary PGCs,
      treated at least surgically, between 1997 and 2010. We assessed the
      clinicopathological associations of IGLN metastases, their prognostic
      significance, and predictive value in the diagnosis of occult neck lymph node
      metastases RESULTS: Twenty-four (25.26%) patients had IGLN metastases. This
      feature was significantly more prevalent in patients with advanced pT status (P =
      .01), pN status (P < .01), and overall stage (P < .001); high-risk carcinomas (P
      = .01); as well as in patients with treatment failures (P < .01). IGLN
      involvement was significantly associated with decreased univariate disease-free
      survival (P < .001). Positive and negative predictive values and accuracy for
      IGLN involvement in the detection of occult neck lymph node metastases were
      63.64%, 90.48%, and 84.91%, respectively. The diagnostic values were generally
      higher in patients with low-risk subtype of PGCs. CONCLUSIONS: IGLN involvement
      provides prognostic information and is associated with advanced tumoral stage and
      higher risk of recurrence. This feature could be used as a potential readout to
      determine whether a neck dissection in clinically negative neck lymph nodes is
      needed or not. LEVEL OF EVIDENCE: 4.

PMID- 25946396
TI  - Bipolar disorder prevalence: a systematic review and meta-analysis of the
      literature.
AB  - OBJECTIVE: Bipolar disorder (BD) is common in clinical psychiatric practice, and
      several studies have estimated its prevalence to range from 0.5 to 5% in
      community-based samples. However, no systematic review and meta-analysis of the
      prevalence of BD type 1 and type 2 has been published in the literature. We
      carried out a systematic review and meta-analysis of the lifetime and 1-year
      prevalence of BD type 1 and type 2 and assessed whether the prevalence of BD
      changed according to the diagnostic criteria adopted (DSM-III, DSM-III-R vs. DSM
      IV). METHODS: We searched MEDLINE, Scopus, Web of Science, PsycINFO, and the
      reference lists of identified studies. The analyses included 25 population- or
      community-based studies and 276,221 participants. RESULTS: The pooled lifetime
      prevalence of BD type 1 was 1.06% (95% confidence interval [95%CI] 0.81-1.31) and
      that of BD type 2 was 1.57% (95%CI 1.15-1.99). The pooled 1-year prevalence was
      0.71% (95%CI 0.56-0.86) for BD type 1 and 0.50% (95%CI 0.35-0.64) for BD type 2.
      Subgroup analysis showed a significantly higher lifetime prevalence of BD type 1
      according to the DSM-IV criteria compared to the DSM-III and DSM-IIIR criteria (p
      < 0.001). CONCLUSION: This meta-analysis confirms that estimates of BD type 1 and
      type 2 prevalence are low in the general population. The increase in prevalence
      from DSM-III and DSM-III-R to DSM-IV may reflect different factors, such as minor
      changes in diagnostic operationalization, use of different assessment
      instruments, or even a genuine increase in the prevalence of BD.

PMID- 25946397
TI  - The construct of psychopathy in a Chilean prison population.
AB  - OBJECTIVE: To test the four-factor model of the Hare Psychopathy Checklist -
      Revised (PCL-R) empirical construct of psychopathy in a Chilean prison population
      by using instruments that supply different types of data. METHODS: Two hundred
      and nine male inmates of the Prison of Los Andes, Chile, were evaluated.
      Confirmatory factor analysis was carried out with the PCL-R and the Self-Report
      of Psychopathy - III - Short Form (SRP-III-SF). RESULTS: The distributions of
      total PCL-R and SRP-III-SF scores were normal (Kolmorogov-Smirnov [K-S] = 1.04, p
      = 0.230; K-S = 0.812, p = 0.525, respectively), with means of 20.9 +/- 6.8 for
      the former and 61.6 +/- 15.2 for the latter. Model fit was good for the PCL-R
      (Tucker Lewis index [TLI] = 0.96; root mean square error of approximation [RMSEA]
      = 0.04) and for the SRP-SF (TLI = 0.94, RMSEA = 0.04). CONCLUSIONS: The results
      obtained with the PCL-R and the SRP-SF showed adequate fit to the empirical four
      factor model of psychopathy and support this model. As foreseeable, fit was
      better for the PCL-R, which combines several sources of information.

PMID- 25946398
TI  - Determinants of adherence to treatment in first-episode psychosis: a
      comprehensive review.
AB  - OBJECTIVE: To conduct a comprehensive review of current evidence on factors for
      nonadherence to treatment in individuals with first-episode psychosis (FEP).
      METHODS: MEDLINE, LILACS, PsycINFO, and SciELO databases were searched with the
      keywords first episode psychosis, factor, adherence, nonadherence, engagement,
      disengagement, compliance, and intervention. References of selected studies were
      consulted for relevant articles. RESULTS: A total of 157 articles were screened,
      of which 33 articles were retained for full review. The factors related to
      nonadherence were: a) patient-related (e.g., lower education level, persistent
      substance use, forensic history, unemployment, history of physical abuse); b)
      environment-related (e.g., no family involved in treatment, social adjustment
      difficulties); c) medication-related (e.g., rapid remission of negative symptoms
      when starting treatment, therapeutic alliance); and d) illness-related (e.g.,
      more positive symptoms, more relapses). Treatment factors that improve adherence
      include a good therapeutic alliance and a voluntary first admission when
      hospitalization occurs. CONCLUSION: The results of this review suggest that
      nonadherence to treatment in FEP is multifactorial. Many of these factors are
      modifiable and can be specifically targeted in early intervention programs. Very
      few studies have assessed strategies to raise adherence in FEP.

PMID- 25946400
TI  - Two clusters of child molesters based on impulsiveness.
AB  - OBJECTIVE: High impulsiveness is a general problem that affects most criminal
      offenders and is associated with greater recidivism risk. A cluster analysis of
      impulsiveness measured by the Barratt Impulsiveness Scale - Version 11 (BIS-11)
      was performed on a sample of hands-on child molesters. METHODS: The sample
      consisted of 208 child molesters enrolled in two different sectional studies
      carried out in Sao Paulo, Brazil. Using three factors from the BIS-11, a k-means
      cluster analysis was performed using the average silhouette width to determine
      cluster number. Direct logistic regression was performed to analyze the
      association of criminological and clinical features with the resulting clusters.
      RESULTS: Two clusters were delineated. The cluster characterized by higher
      impulsiveness showed higher scores on the Sexual Screening for Pedophilic
      Interests (SSPI), Static-99, and Sexual Addiction Screening Test. CONCLUSIONS:
      Given that child molesters are an extremely heterogeneous population, the "number
      of victims" item of the SSPI should call attention to those offenders with the
      highest motor, attentional, and non-planning impulsiveness. Our findings could
      have implications in terms of differences in therapeutic management for these two
      groups, with the most impulsive cluster benefitting from psychosocial strategies
      combined with pharmacological interventions.

PMID- 25946399
TI  - Personality disorders in euthymic bipolar patients: a systematic review.
AB  - OBJECTIVE: To identify, by means of a systematic review, the frequency with which
      comorbid personality disorders (PDs) have been assessed in studies of euthymic
      bipolar patients. METHODS: PubMed, ciELO and PsychINFO databases were searched
      for eligible articles published between 1997 and 2013. After screening 1,249
      empirical papers, two independent reviewers identified three articles evaluating
      the frequency of PDs in patients with bipolar disorders assessed in a state of
      euthymia. RESULTS: The total sample comprised 376 euthymic bipolar patients, of
      whom 155 (41.2%) had at least one comorbid PD. Among them, we found 87 (23.1%) in
      cluster B, 55 (14.6%) in cluster C, and 25 (6.6%) in cluster A. The frequencies
      of PD subtypes were: borderline, 38 (10.1%); histrionic, 29 (7.7%); obsessive
      compulsive, 28 (7.4%); dependent, 19 (5%); narcissistic, 17 (4.5%); schizoid,
      schizotypal, and avoidant, 11 patients each (2.95%); paranoid, five (1.3%); and
      antisocial, three (0.79%). CONCLUSION: The frequency of comorbid PD was high
      across the spectrum of euthymic bipolar patients. In this population, the most
      common PDs were those in cluster B, and the most frequent PD subtype was
      borderline, followed by histrionic and obsessive-compulsive.

PMID- 25946401
TI  - Facile synthesis of dumbbell-shaped multi-compartment nanoparticles.
AB  - In this article we report on the controlled synthesis of asymmetric lemon-shaped
      and dumbbell-shaped multi-compartment nanoparticles (MCPs) with a reactive
      surface and interesting morphology. In our approach we utilize partial coating of
      hematite ellipsoids with a hydrophobic polymer layer followed by selective silica
      deposition on the non-coated surface. Ellipsoidal hematite particles provide a
      non-centric asymmetry, which is strongly enhanced during the seeded emulsion
      polymerization. The asymmetric growth of polymers on the hematite particle
      surface is driven by phase separation phenomena, which lead to a reduction of the
      interfacial tension. We found the tips of the hematite ellipsoids to be uncovered
      after polymerization. A selective deposition of silica onto the free tips leads
      to dumbbell-shaped particles with hydrophilic and hydrophobic parts. 

PMID- 25946403
TI  - The Lower-Extremity Functional Test and Lower-Quadrant Injury in NCAA Division
      III Athletes: A Descriptive and Epidemiologic Report.
AB  - CONTEXT: The Lower-Extremity Functional Test (LEFT) has been used to assess
      readiness to return to sport after a lower-extremity injury. Current
      recommendations suggest that women should complete the LEFT in 135 s (average;
      range 120-150 s) and men should complete the test in 100 s (average; range 90-125
      s). However, these estimates are based on limited data and may not be reflective
      of college athletes. Thus, additional assessment, including normative data, of
      the LEFT in sport populations is warranted. OBJECTIVE: To examine LEFT times
      based on descriptive information and off-season training habits in NCAA Division
      III (DIII) athletes. In addition, this study prospectively examined the LEFT's
      ability to discriminate sport-related injury occurrence. DESIGN: Descriptive
      epidemiology. SETTING: DIII university. SUBJECTS: 189 DIII college athletes (106
      women, 83 men) from 15 teams. MAIN OUTCOME MEASURES: LEFT times, preseason
      questionnaire, and time-loss injuries during the sport season. RESULTS: Men
      completed the LEFT (105 +/- 9 s) significantly faster than their female
      counterparts (117 +/- 10 s) (P < .0001). Female athletes who reported >3-5 h/wk
      of plyometric training during the off-season had significantly slower LEFT scores
      than those who performed <=3 h/wk of plyometric training (P = .03). The overall
      incidence of a lower-quadrant (LQ) time-loss injury for female athletes was
      4.5/1000 athletic exposures (AEs) and 3.7/1000 AEs for male athletes. Female
      athletes with slower LEFT scores (>=118 s) experienced a higher rate of LQ time
      loss injuries than those with faster LEFT scores (<=117 s) (P = .03). CONCLUSION:
      Only off-season plyometric training practices seem to affect LEFT score times
      among female athletes. Women with slower LEFT scores are more likely to be
      injured than those with faster LEFT scores. Injury rates in men were not
      influenced by performance on the LEFT.

PMID- 25946402
TI  - Immune dysfunction in Niemann-Pick disease type C.
AB  - Lysosomal storage diseases are inherited monogenic disorders in which lysosome
      function is compromised. Although individually very rare, they occur at a
      collective frequency of approximately one in five thousand live births and
      usually have catastrophic consequences for health. The lysosomal storage diseases
      Niemann-Pick disease type C (NPC) is caused by mutations predominantly in the
      lysosomal integral membrane protein NPC1 and clinically presents as a progressive
      neurodegenerative disorder. In this article we review data that demonstrate
      significant dysregulation of innate immunity in NPC, which occurs both in
      peripheral organs and the CNS. In particular pro-inflammatory responses promote
      disease progression and anti-inflammatory drugs provide benefit in animal models
      of the disease and are an attractive target for clinical intervention in this
      disorder. Niemann-Pick disease type C is a rare, devastating, inherited lysosomal
      storage disease with a unique cellular phenotype characterized by lysosomal
      accumulation of sphingosine, various glycosphingolipids and cholesterol and a
      reduction in lysosomal calcium. In this review we highlight the impact of the
      disease on innate immune activities in both the central nervous system (CNS) and
      peripheral tissues and discuss their contributions to pathology and the
      underlying mechanisms. 

PMID- 25946404
TI  - Genetics of second-generation antipsychotic and mood stabilizer-induced weight
      gain in bipolar disorder: common and specific effects of key regulators of fat
      mass homoeostasis genes.
AB  - OBJECTIVE: Second-generation antipsychotics (SGAP) and mood stabilizers (MS) are
      prescribed widely for the treatment of bipolar disorder, but they are associated
      with the risk of relevant side-effects, among which is weight gain. The
      identification of genes that predispose to weight gain would represent a useful
      tool to evaluate the risk-benefit ratio of treatment. MATERIALS AND METHODS: This
      study investigated the genetic factors associated with weight gain in bipolar
      patients treated with SGAP, MS and their combinations (n=486). Single-nucleotide
      polymorphisms belonging to 16 candidate genes supported by the literature were
      investigated in the Systematic Treatment Enhancement Program for Bipolar Disorder
      (STEP-BD) genome-wide dataset. Linear regression models were constructed
      including age, sex, initial weight and prescription of SGAP at high risk for
      inducing weight gain (olanzapine or clozapine) as covariates. Genes harbouring
      single-nucleotide polymorphisms associated with phenotypes were investigated by a
      pathway analysis. RESULTS: No association was found between phenotypes and
      individual polymorphisms or pathways after multiple-test correction. HTR2C, LEP,
      FTO and TBC1D1 represented the top genes for weight gain during treatment with a
      SGAP and/or MS. A genome-wide signal (FTO rs9930506) associated previously with
      obesity was associated with psychotropic-induced weight gain. The genes that
      influenced both SGAP and MS weight gain were FTO, TBC1D1, MTHFR and HRH1. ADCY9,
      ADCY5 and PRKAG2 were interesting candidate genes that emerged from the pathway
      analysis. CONCLUSION: This study was the first to compare the genes involved in
      SGAP-induced and MS-induced weight gain. Individual genes probably play a limited
      role in psychotropic-induced weight gain; further studies should focus on the
      extension from known candidate genes to wider groups of molecular pathways.

PMID- 25946406
TI  - Unsymmetrical Donor-Acceptor-Acceptor-pi-Donor Type Benzothiadiazole-Based Small
      Molecule for a Solution Processed Bulk Heterojunction Organic Solar Cell.
AB  - A D1-A-A'-pi-D2 type (D = donor; A = acceptor) unsymmetrical small molecule
      denoted as BTD3 containing different end group donor moieties has been designed
      and synthesized for use as a donor in the solution processable bulk
      heterojunction (BHJ) solar cell. The BTD3 exhibits a low HOMO-LUMO gap of 1.68 eV
      and deeper HOMO energy level (-5.5 eV). Its LUMO energy level (-3.65 eV) is
      compatible with the LUMO level of PC71BM to facilitate the electron transfer from
      BTD3 to PC71BM in the BHJ solar cell. The solution processed BHJ solar cell with
      optimized BTD3:PC71BM active layer processed with THF solvent exhibited a PCE of
      3.15% with Jsc = 7.45 mA/cm(2), Voc = 0.94 V, and FF = 0.45. Moreover, the device
      with optimized concentration of 3 vol. % 1-chloronaphthalene (CN) additive, i.e.,
      CN/THF, showed significant enhancement in PCE up to 4.61% (Jsc = 9.48 mA/cm(2),
      Voc = 0.90 V, and FF = 0.54). The improvement in the PCE has been attributed to
      the appropriate nanoscale phase separation morphology, balance charge transport,
      and enhancement in the light harvesting ability of the active layer. 

PMID- 25946405
TI  - Variation in genes controlling warfarin disposition and response in American
      Indian and Alaska Native people: CYP2C9, VKORC1, CYP4F2, CYP4F11, GGCX.
AB  - OBJECTIVES: Pharmacogenetic testing is projected to improve health outcomes and
      reduce the cost of care by increasing therapeutic efficacy and minimizing drug
      toxicity. American Indian and Alaska Native (AI/AN) people historically have been
      excluded from pharmacogenetic research and its potential benefits, a deficiency
      we sought to address. The vitamin K antagonist warfarin is prescribed for
      prevention of thromboembolic events, although its narrow therapeutic index and
      wide interindividual variability necessitate close monitoring of drug response.
      Therefore, we were interested in variation in CYP2C9, VKORC1, CYP4F2, CYP4F11,
      and GGCX, which encode enzymes important for the activity of warfarin and
      synthesis of vitamin K-dependent blood clotting factors. METHODS: We resequenced
      these genes in 188 AI/AN people in partnership with Southcentral Foundation in
      Anchorage, Alaska and 94 Yup'ik people living in the Yukon-Kuskokwim Delta of
      southwest Alaska to identify known or novel function-disrupting variation. We
      conducted genotyping for specific single nucleotide polymorphisms in larger
      cohorts of each study population (380 and 350, respectively). RESULTS: We
      identified high frequencies of the lower-warfarin dose VKORC1 haplotype (-1639G>A
      and 1173C>T) and the higher-warfarin dose CYP4F2*3 variant. We also identified
      two relatively common, novel, and potentially function-disrupting variants in
      CYP2C9 (M1L and N218I), which, along with CYP2C9*3, CYP2C9*2, and CYP2C9*29,
      predict that a significant proportion of AI/AN people will have decreased CYP2C9
      activity. CONCLUSION: Overall, we predict a lower average warfarin dose
      requirement in AI/AN populations in Alaska than that seen in non-AI/AN
      populations of the USA, a finding consistent with clinical experience in Alaska.

PMID- 25946407
TI  - Editorial: a simple faecal preparation protocol for faecal microbiota
      transplantation.

PMID- 25946409
TI  - Bacterial rapid identification with matrix assisted laser desorption/ionization
      time-of-flight mass spectrometry: development of an 'in-house method' and
      comparison with Bruker Sepsityper((r)) kit.
AB  - OBJECTIVE: The objective of this study was to compare an in-house matrix-assisted
      laser desorption ionization with time of flight (MALDI-TOF) method and a
      commercial MALDI-TOF kit (Sepsityper((r)) kit) for direct bacterial
      identification in positive blood cultures. We also evaluated the time saved and
      the cost associated with the rapid identification techniques. METHODS: We used
      the BACTEC((r)) automated system for detecting positive blood cultures. Direct
      identification using Sepsityper kit and the in-house method were compared with
      conventional identification by MALDI-TOF using pure bacterial culture on the
      solid phase. We also evaluated different cut-off scores for rapid bacterial
      identification. RESULTS: In total, 127 positive blood vials were selected. The
      rate of rapid identification with the MALDI Sepsityper kit was 25.2% with the
      standard cut-off and 33.9% with the enlarged cut-off, while the results for the
      in-house method were 44.1 and 61.4%, respectively. Error rates with the enlarged
      cut-off were 6.98 (n = 3) and 2.56% (n = 2) for Sepsityper and the in-house
      method, respectively. Identification rates were higher for gram-negative
      bacteria. DISCUSSION: Direct bacterial identification succeeded in supplying
      rapid identification of the causative organism in cases of sepsis. The time taken
      to obtain a result was nearly 24  hours shorter for the direct bacterial
      identification methods than for conventional MALDI-TOF on solid phase culture.
      Compared with the Sepsityper kit, the in-house method offered better results and
      fewer errors, was more cost-effective and easier to use.

PMID- 25946410
TI  - Chiral Metal Nanoparticle Systems as Heterogeneous Catalysts beyond Homogeneous
      Metal Complex Catalysts for Asymmetric Addition of Arylboronic Acids to
      alpha,beta-Unsaturated Carbonyl Compounds.
AB  - We describe the use of chiral metal nanoparticle systems, as novel heterogeneous
      chiral catalysts for the asymmetric 1,4-addition of arylboronic acids to
      alpha,beta-unsaturated carbonyl compounds, as representative C-C bond-forming
      reactions. The reactions proceeded smoothly to afford the corresponding beta
      arylated products in high to excellent yields and outstanding
      enantioselectivities with wide substrate scope. Remarkably, the nanoparticle
      catalysts showed performance in terms of yield, enantioselectivity, and catalytic
      turnover that was superior to that of the corresponding homogeneous metal
      complexes. The catalyst can be successfully recovered and reused in a gram-scale
      synthesis with low catalyst loading without significant loss of activity. The
      nature of the active species was investigated, and we found that characteristic
      features of the nanoparticle system were totally different from those of the
      metal complex system. 

PMID- 25946408
TI  - Liver X receptors contribute to periodontal pathogen-elicited inflammation and
      oral bone loss.
AB  - Periodontal diseases are chronic oral inflammatory diseases that are
      polymicrobial in nature. The presence of specific bacteria in subgingival plaque
      such as Porphyromonas gingivalis is associated with microbial dysbiosis and the
      modulation of host immune response. Bacterially elicited innate immune activation
      and inflammation are key elements implicated in the destruction of soft and hard
      tissues supporting the teeth. Liver X receptors (LXRs) are nuclear hormone
      receptors with important function in lipid homeostasis, inflammation, and host
      response to infection; however, their contribution to chronic inflammatory
      diseases such as periodontal disease is not understood. The aim of this study was
      to define the contribution of LXRs in the development of immune response to P.
      gingivalis and to assess the roles that LXRs play in infection-elicited oral bone
      loss. Employing macrophages, we observed that P. gingivalis challenge led to
      reduced LXRalpha and LXRbeta gene expression compared with that observed with
      unchallenged wild-type cells. Myeloid differentiation primary response gene 88
      (MyD88)-independent, Toll/interleukin-1 receptor-domain-containing adapter
      inducing interferon-beta (TRIF)-dependent signaling affected P. gingivalis
      mediated reduction in LXRalpha expression, whereas neither pathway influenced the
      P. gingivalis effect on LXRbeta expression. Employing LXR agonist and mice
      deficient in LXRs, we observed functional effects of LXRs in the development of a
      P. gingivalis-elicited cytokine response at the level of the macrophage, and
      participation of LXRs in P. gingivalis-elicited oral bone loss. These findings
      identify novel importance for LXRs in the pathogenesis of P. gingivalis infection
      elicited inflammation and oral bone loss.

PMID- 25946411
TI  - Potential Economic Impact of Using a Restrictive Transfusion Trigger Among
      Patients Undergoing Major Abdominal Surgery.
AB  - IMPORTANCE: Transfusion practice among surgeons varies despite several evidence
      based recommendations supporting the restrictive use of blood products.
      OBJECTIVE: To define the economic impact of liberal blood transfusions as
      assessed through an analysis of hemoglobin (Hb) triggers. DESIGN, SETTING, AND
      PARTICIPANTS: Using a prospective database, data on Hb levels that triggered a
      transfusion and overall blood product use were obtained for patients undergoing
      pancreas, liver, or colorectal surgery between January 1, 2010, and August 31,
      2013, at Johns Hopkins Hospital. An economic analysis was performed using a range
      of costs for a single unit of packed red blood cells (PRBCs) based on actual
      institutional acquisition costs ($220/unit) and an estimated activity-based cost
      ($760/unit). Guidelines define a liberal Hb trigger as transfusion of PRBCs for
      an intraoperative Hb level of 10 g/dL or greater or a postoperative Hb level of 8
      g/dL or greater (to convert to grams per liter, multiply by 10.0). MAIN OUTCOMES
      AND MEASURES: Numbers of surgical patients who received PRBC transfusion,
      estimated cost per transfusion, and estimated cost of excessive blood
      transfusions. RESULTS: Among 3027 patients, 942 (31.1%) received at least 1 PRBC
      transfusion, intraoperatively in 264 patients (8.7%), postoperatively in 429
      (14.2%), or both in 249 (8.2%). A total of 4000 units of PRBCs (range, 0-167
      units/patient) were transfused in the intraoperative (1581 units [39.5%]) and
      postoperative (2419 units [60.5%]) periods. Estimated total costs of PRBC
      transfusion ranged from $880,000 to $3,040,000, with marked variation in costs
      per patient across procedure type and surgeon. Among the 942 patients who
      received a transfusion, 456 units (11.4%) were transfused using a liberal trigger
      (intraoperative, 122 patients [13.0%]; postoperative, 79 patients [8.4%]). By
      adopting a restrictive trigger, total overall PRBC transfusion costs may have
      been reduced by $100,320 to $346,560 during the 44-month study period or $27,360
      to $94,516 per year for patients undergoing a pancreas, liver, or colorectal
      resection. CONCLUSIONS AND RELEVANCE: More than 1 in 10 units of PRBCs were
      transfused using a liberal Hb trigger. Patient blood management programs should
      aim to identify and reduce liberal transfusion practice in the surgical patient.

PMID- 25946412
TI  - Foraging-Based Enrichment Promotes More Varied Behaviour in Captive Australian
      Fur Seals (Arctocephalus pusillus doriferus).
AB  - During wild foraging, Australian fur seals (Arctocephalus pusillus doriferus)
      encounter many different types of prey in a wide range of scenarios, yet in
      captive environments they are typically provided with a narrower range of
      opportunities to display their full repertoire of behaviours. This study aimed to
      quantitatively explore the effect of foraging-based enrichment on the behaviour
      and activity patterns displayed by two captive Australian fur seals at Melbourne
      Zoo, Australia. Food was presented as a scatter in open water, in a free-floating
      ball device, or in a static box device, with each treatment separated by control
      trials with no enrichment. Both subjects spent more time interacting with the
      ball and static box devices than the scatter feed. The total time spent pattern
      swimming was reduced in the enrichment treatments compared to the controls, while
      the time spent performing random swimming behaviours increased. There was also a
      significant increase in the total number of bouts of behaviour performed in all
      three enrichment treatments compared to controls. Each enrichment method also
      promoted a different suit of foraging behaviours. Hence, rather than choosing one
      method, the most effective way to increase the diversity of foraging behaviours,
      while also increasing variation in general activity patterns, is to provide seals
      with a wide range of foraging scenarios where food is encountered in different
      ways. 

PMID- 25946413
TI  - Low-birefringent and highly tough nanocellulose-reinforced cellulose triacetate.
AB  - Improvement of the mechanical and thermal properties of cellulose triacetate
      (CTA) films is required without sacrificing their optical properties. Here,
      poly(ethylene glycol) (PEG)-grafted cellulose nanofibril/CTA nanocomposite films
      were fabricated by casting and drying methods. The cellulose nanofibrils were
      prepared by 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-mediated oxidation, and
      amine-terminated PEG chains were grafted onto the surfaces of the TEMPO-oxidized
      cellulose nanofibrils (TOCNs) by ionic bonds. Because of the nanosize effect of
      TOCNs with a uniform width of ~3 nm, the PEG-TOCN/CTA nanocomposite films had
      high transparency and low birefringence. The grafted PEG chains enhanced the
      filler-matrix interactions and crystallization of matrix CTA molecules, resulting
      in the Young's modulus and toughness of CTA film being significantly improved by
      PEG-grafted TOCN addition. The coefficient of thermal expansion of the original
      CTA film was mostly preserved even with the addition of PEG-grafted TOCNs. These
      results suggest that PEG-TOCNs are applicable to the reinforcement for
      transparent optical films. 

PMID- 25946415
TI  - Is There an Optimal Proximal Locking Screw Length in Retrograde Intramedullary
      Femoral Nailing? Can We Stop Measuring for These Screws?
AB  - Insertion of locking screws through the proximal thigh while locking retrograde
      femoral nails is arguably more difficult and traumatic to local tissues than
      locking at other intramedullary nail sites. The purpose of this study was to
      evaluate whether a "standard" screw length for proximal interlocking of
      retrograde nails is possible, therefore assessing whether the act of measuring
      for these screws can be omitted. This article retrospective evaluates screw
      position and estimated proximal locking screw length in patients undergoing
      retrograde nailing using a large radiographically measured computed tomography
      cohort, with validation through a smaller clinical cohort. According to these
      data, it seems reasonable to skip depth gauge measurement during anteroposterior
      interlocking of retrograde femoral nails and insert a standard length screw based
      on location relative to the lesser trochanter. This should decrease the amount of
      local trauma to the patient at the locking screw site while increasing operating
      room efficiency by avoiding what can often become a difficult step during the
      procedure. 

PMID- 25946414
TI  - Rapid Self-Integrating, Injectable Hydrogel for Tissue Complex Regeneration.
AB  - A novel rapid self-integrating, injectable, and bioerodible hydrogel is developed
      for bone-cartilage tissue complex regeneration. The hydrogels are able to self
      integrate to form various structures, as can be seen after dying some hydrogel
      disks pink with rodamine. This hydrogel is demonstrated to engineer cartilage
      bone complex. 

PMID- 25946418
TI  - The Representation and Parametrization of Orthogonal Matrices.
AB  - Four representations and parametrizations of orthogonal matrices Q ? R(m*n) in
      terms of the minimal number of essential parameters {phi} are discussed: the
      exponential representation, the Householder reflector representation, the Givens
      rotation representation, and the rational Cayley transform representation. Both
      square n = m and rectangular n < m situations are considered. Two separate kinds
      of parametrizations are considered: one in which the individual columns of Q are
      distinct, the Stiefel manifold, and the other in which only span(Q) is
      significant, the Grassmann manifold. The practical issues of numerical stability,
      continuity, and uniqueness are discussed. The computation of Q in terms of the
      essential parameters {phi}, and also the extraction of {phi} for a given Q are
      considered for all of the parametrizations. The transformation of gradient arrays
      between the Q and {phi} variables is discussed for all representations. It is our
      hope that developers of new methods will benefit from this comparative
      presentation of an important but rarely analyzed subject.

PMID- 25946419
TI  - Induced Phytoextraction of Lead Through Chemical Manipulation of Switchgrass and
      Corn; Role of Iron Supplement.
AB  - The effects of combined chemical application of benomyl,
      ethylenedianinetetraacetate (EDTA), and iron (Fe) (foliar and root) on lead (Pb)
      phytoextraction by switchgrass (Panicum virgatum) and corn (Zea mays) was
      examined. Switchgrass was grown in Pb-contaminated urban topsoil with the
      following treatments: (C) Control, (B) benomyl, (E) EDTA, (F) foliar-Fe, (BE)
      benomyl + EDTA, (BF) benomyl + foliar-Fe, (FE) foliar-Fe + EDTA, (BFE) benomyl +
      foliar-Fe + EDTA. Corn was grown in sand-culture supplemented with Pb (500 mg kg(
      1)) with the following treatments: (C) control, (B) benomyl, (E) EDTA, (F) root
      Fe, (BE) benomyl + EDTA, (BF) benomyl + root-Fe, (FE) root-iron + EDTA, and,
      (BFE) benomyl + root-Fe + EDTA. All treatments were replicated three times and
      pots were arranged in a completely randomized design. Plants were analyzed for
      element concentration (Fe, Zn, P, and Pb) using either inductively coupled plasma
      (argon) atomic emission spectroscopy (ICP-AES) or graphite furnace atomic
      absorption spectrometer. Iron supplementation (foliar and root) affected Pb
      translocation in plants. Foliar-Fe treatment increased translocation ratio of Pb
      (TF-Pb) significantly compared to other treatments with the exception of plants
      treated with benomyl and BF. Root-Fe treatment in combination with EDTA (FE)
      increased TF-Pb significantly compared to other treatments. Phytoextraction was
      improved by the combined chemical application; plants treated with BFE treatment
      increased Pb-total-phytoextraction by 424% compared to Control plants. 

PMID- 25946426
TI  - MAGPI: A framework for maximum likelihood MR phase imaging using multiple receive
      coils.
AB  - PURPOSE: Combining MR phase images from multiple receive coils is a challenging
      problem, complicated by ambiguities introduced by phase wrapping, noise, and the
      unknown phase-offset between the coils. Various techniques have been proposed to
      mitigate the effect of these ambiguities but most of the existing methods require
      additional reference scans and/or use ad hoc post-processing techniques that do
      not guarantee any optimality. THEORY AND METHODS: Here, the phase estimation
      problem is formulated rigorously using a maximum-likelihood (ML) approach. The
      proposed framework jointly designs the acquisition-processing chain: the
      optimized pulse sequence is a single multiecho gradient echo scan and the
      corresponding postprocessing algorithm is a voxel-per-voxel ML estimator of the
      underlying tissue phase. RESULTS: Our proposed framework (Maximum AmbiGuity
      distance for Phase Imaging, MAGPI) achieves substantial improvements in the phase
      estimate, resulting in phase signal-to-noise ratio (SNR) gains by up to an order
      of magnitude compared to existing methods. CONCLUSION: The advantages of MAGPI
      are: (1) ML-optimal combination of phase data from multiple receive coils,
      without a reference scan; (2) voxel-per-voxel ML-optimal estimation of the
      underlying tissue phase, without the need for phase unwrapping or image
      smoothing; and (3) robust dynamic estimation of channel-dependent phase-offsets.

PMID- 25946427
TI  - Amine-Based Interfacial Molecules for Inverted Polymer-Based Optoelectronic
      Devices.
AB  - The change in the work function (WF) of ZnO with amine-based interfacial mole
      cules (AIM) can be controlled by the number of amine groups. AIM with a larger
      amine group can induce a stronger interface dipole between the amine groups and
      the ZnO surface, leading to a greater reduction of the WF. 

PMID- 25946428
TI  - Nanosized {Pd4(MU4-C)}Pd32(CO)28(PMe3)14 Containing Tetrahedrally Deformed Pd4
      Cage with Encapsulated Carbide Atom: Formal Substitution of Geometrically
      Analogous Interior Au4 Entity in Isostructural Au4Pd32(CO)28(PMe3)14 by
      Electronically Equivalent Pd4(MU4-C) and Computational/Catalytic Implications.
AB  - This first homopalladium carbido cluster, {Pd4(MU4-C)}Pd32(CO)28(PMe3)14 (1), was
      isolated (3-7% yields) from an ultimately simplified procedure-the reaction of
      CHCl3 under N2 with either Pd8(CO)8(PMe3)7 or Pd10(CO)12(PMe3)6 at room
      temperature. Charge-coupled device (CCD) X-ray diffraction data at 100 K for
      1.2.5 C6H14 (1a) and 1.3 CHCl3 (1b) produced closely related molecular parameters
      for 1. This {Pd4C}Pd32 cluster (1) possesses a highly unusual tetracoordinated
      carbide atom that causes a major distortion of a central regular Pd4 tetrahedron
      into a new symmetry type of encapsulated Pd4 cage of pseudo-D2 (222) symmetry.
      Mean Pd-Pd distances for the three pairs of opposite twofold-equivalent Pd-Pd
      tetrahedral-like edges for 1a are 2.71, 2.96, and 3.59 A; the mean of the four Pd
      C distances [range, 1.87(2)-1.94(2) A] is 1.91 A. An astonishing molecular
      feature is that this {Pd4C}Pd32 cluster (1) is an isostructural and
      electronically equivalent analogue of the nanosized Au4Pd32(CO)28(PMe3)14 (2).
      Cluster 2, likewise a pseudo-D2 molecule, contains a geometrically analogous
      tetrahedrally deformed interior Au4 entity encapsulated within an identical
      Pd32(CO)28(PMe3)14 shell; mean distances for the three corresponding symmetry
      equivalent pairs of slightly smaller opposite tetrahedral-distorted Au-Au edges
      are 2.64, 2.90, and 3.51 A. A computational study by both a natural population
      analysis (NPA) and an atoms-in-molecules (AIM) method performed on model
      analogues {Pd4C}Pd32(CO)28(PH3)14 (1-mod) and Au4Pd32(CO)28(PH3)14 (2-mod)
      suggested that the negatively charged Au4 entity in 2-mod may be described as two
      weakly interacting electron-pair Au2 intradimers. In contrast, an NPA of the
      {Pd4C} entity in 1-mod revealed that two similarly oriented identical Pd2
      intradimers of 2.71 A are primarily stabilized by Pd-C bonding with a negatively
      charged carbide atom. The isostructural stabilizations of 1 and 2 are then
      attributed to the similar sizes, shapes, and overall negative charge
      distributions of the electronically equivalent interior {Pd4C} and Au4 entities.
      This resulting remarkable structural/electronic equivalency between 1 and 2 is
      consistent with the greatly improved performances of commercial palladium
      catalysts for vinyl acetate synthesis by gold-atom incorporation to suppress
      carbonization of the Pd atoms, namely, that the extra Au 6s(1) valence electron
      of each added Au atom provides an effective "negative charge protection" against
      electron-donating carbon atoms forming Pd carbido species such as {Pd4C}. 

PMID- 25946430
TI  - A laboratory evaluation of bulk-fill versus traditional multi-increment-fill
      resin-based composites.

PMID- 25946429
TI  - Transgenic alfalfa plants expressing the sweetpotato Orange gene exhibit enhanced
      abiotic stress tolerance.
AB  - Alfalfa (Medicago sativa L.), a perennial forage crop with high nutritional
      content, is widely distributed in various environments worldwide. We recently
      demonstrated that the sweetpotato Orange gene (IbOr) is involved in increasing
      carotenoid accumulation and enhancing resistance to multiple abiotic stresses. In
      this study, in an effort to improve the nutritional quality and environmental
      stress tolerance of alfalfa, we transferred the IbOr gene into alfalfa (cv.
      Xinjiang Daye) under the control of an oxidative stress-inducible peroxidase
      (SWPA2) promoter through Agrobacterium tumefaciens-mediated transformation. Among
      the 11 transgenic alfalfa lines (referred to as SOR plants), three lines (SOR2,
      SOR3, and SOR8) selected based on their IbOr transcript levels were examined for
      their tolerance to methyl viologen (MV)-induced oxidative stress in a leaf disc
      assay. The SOR plants exhibited less damage in response to MV-mediated oxidative
      stress and salt stress than non-transgenic plants. The SOR plants also exhibited
      enhanced tolerance to drought stress, along with higher total carotenoid levels.
      The results suggest that SOR alfalfa plants would be useful as forage crops with
      improved nutritional value and increased tolerance to multiple abiotic stresses,
      which would enhance the development of sustainable agriculture on marginal lands.

PMID- 25946431
TI  - Evaluation of four dental clinical spectrophotometers relative to human shade
      observation.

PMID- 25946432
TI  - Corrigendum.
AB  - Article title: Autophagy inhibition promotes defective neosynthesized proteins
      storage in ALIS, and induces redirection toward proteasome processing and MHCI
      restricted presentation. Authors: Till Wenger, Seigo Terawaki, Voahirana
      Camosseto, Ronza Abdelrassoul, Anna Mies, Nadia Catalan, Nuno Claudio, Giovanna
      Clavarino, Aude de Gassart, Francesca de Angelis Rigotti, Evelina Gatti, and
      Philippe Pierre. Journal: Autophagy. Bibliometrics: Volume 8, Issue 3, Pages 350
      63. DOI: 10.4161/auto.18806. It has come to our attention that two of the
      microscopy panels in Figure 1B and C in the original version of this article were
      duplicated in error. This duplication did not change the overall interpretation
      of the figures nor the conclusion of the paper. The original staining for
      SQSTM1/p62 in HeLa cells treated with 3MA that was missing in Figure 1B are
      provided below.

PMID- 25946433
TI  - Large-scale multiplex polymerase chain reaction assay for diagnosis of viral
      reactivations after allogeneic hematopoietic stem cell transplantation.
AB  - Viral reactivations following hematopoietic stem cell transplantation are thought
      to result from the breakdown of both cell-mediated and humoral immunity. As a
      result, many viruses could be reactivated individually or simultaneously. Using a
      multiplex polymerase chain reaction (PCR), we prospectively examined many kinds
      of viral DNAs at a time in 105 patients who underwent allogeneic hematopoietic
      stem cell transplantation. In total, 591 whole blood samples were collected
      weekly from pre- to 42 days post-transplantation and the following 13 viruses
      were tested; herpes simplex virus 1 (HSV-1), HSV-2, varicella-zoster virus (VZV),
      Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpes virus 6 (HHV-6),
      HHV-7, HHV-8, adenovirus, BK virus (BKV), JC virus (JCV), parvovirus B19, and
      hepatitis B virus (HBV). Several viral DNAs were detected in 12 patients before
      hematopoietic stem cell transplantation. The detection rate gradually increased
      after transplantation and peaked at 21 days. The most frequently detected virus
      was HHV-6 (n = 63; 60.0%), followed by EBV (n = 11; 10.5%), CMV (n = 11; 10.5%),
      and HHV-7 (n = 9; 8.6%). Adenovirus and HBV were each detected in one patient
      (1.0%). Detection of HHV-6 DNA was significantly more common among patients
      undergoing cord blood transplantation or with steroid treatment. EBV DNA tended
      to be more common in patients treated with anti-thymocyte globulin. Multiplex PCR
      was useful for detecting many viral reactivations after hematopoietic stem cell
      transplantation, simultaneously. Cord blood transplantation, steroid treatment,
      or anti-thymocyte globulin use was confirmed to be risk factors after
      transplantation.

PMID- 25946434
TI  - Pathology of the Pine Wilt Disease Caused by Bursaphelenchus xylophilus.

PMID- 25946436
TI  - Is there life after transcatheter aortic valve replacement?

PMID- 25946435
TI  - Long-term outcomes after transcatheter aortic valve replacement in high-risk
      patients with severe aortic stenosis: the U.K. Transcatheter Aortic Valve
      Implantation Registry.
AB  - OBJECTIVES: The U.K. Transcatheter Aortic Valve Implantation Registry reported 30
      day and 1-year mortality rates of 7.1% and 21.4%, respectively, for patients who
      underwent transcatheter aortic valve replacement (TAVR) in the United Kingdom
      between 2007 and 2009. The study aim was to report long-term outcomes in this
      same cohort of patients. BACKGROUND: There are few data on outcomes beyond 3
      years after TAVR in any notable number of patients. METHODS: Data from all TAVR
      procedures performed in the United Kingdom between January 2007 and December 2009
      were prospectively collected. All-cause mortality status was reported in March
      2014. Mortality tracking was achieved in 97.7% patients. RESULTS: The minimal
      time from replacement to census was 4.1 years, and the maximal time was 7.0
      years. The 3- and 5-year survival rates were 61.2% and 45.5%, respectively.
      Independent predictors of 3-year mortality were renal dysfunction (hazard ratio
      [HR]: 1.65), atrial fibrillation (HR: 1.36), logistic European System for Cardiac
      Operative Risk Evaluation (EuroSCORE) >=18.5 (HR: 1.33), respiratory dysfunction
      (HR: 1.28), and ventricular dysfunction (left ventricular ejection fraction <30%)
      (HR: 1.53). Coronary artery disease (HR: 1.28) and age (HR: 1.03) were additional
      independent predictors of mortality at 5 years. Stroke within 30 days of TAVR was
      the only independent procedural predictor of mortality at 3 and 5 years (HR: 2.17
      at 3 years). Device type, access route, and paravalvular leak did not
      independently predict long-term outcome. CONCLUSIONS: In the large U.K.
      Transcatheter Aortic Valve Implantation Registry, long-term outcomes after TAVR
      are favorable with 3- and 5-year survival rates of 61.2% and 45.5%, respectively.
      Long-term survival after TAVR is largely determined by intrinsic patient factors.
      Other than stroke, procedural variables, including paravalvular aortic leak, did
      not appear to be independent predictors of long-term survival.

PMID- 25946438
TI  - Surgical sutureless and transcatheter aortic valves: hemodynamic performance and
      clinical outcomes in propensity score-matched high-risk populations with severe
      aortic stenosis.
AB  - OBJECTIVES: In propensity score-matched patients with severe aortic stenosis
      treated with surgical aortic valve replacement (AVR) with the 3f Enable
      sutureless prosthesis (Medtronic, Minneapolis, Minnesota) or transcatheter aortic
      valve replacement (TAVR), the hemodynamic performance of both valves and mid-term
      survival of patients were evaluated. BACKGROUND: Data on hemodynamic performance
      of surgical sutureless bioprostheses in high operative risk patients with aortic
      stenosis are scarce. METHODS: Of 258 patients undergoing TAVR or surgical aortic
      valve replacement with the 3f Enable valve, 80 (79 +/- 5 years of age, 100% men)
      were included in the current analysis on the basis of propensity score 1:1
      matching for baseline clinical and hemodynamic characteristics. All patients had
      hemodynamic echocardiographic evaluation at baseline and discharge. Mid-term
      survival was analyzed. RESULTS: Compared with the 3f Enable valve, TAVR
      prostheses (Edwards SAPIEN XT [Edwards Lifesciences, Irvine, California] and
      CoreValve [Medtronic]) had larger effective orifice area index (1.00 +/- 0.30
      cm(2)/m(2) vs. 0.76 +/- 0.22 cm(2)/m(2); p < 0.001), lower pressure gradient
      (8.14 +/- 4.21 mm Hg vs. 10.72 +/- 4.01 mm Hg; p = 0.006), less frequent
      prosthesis-patient mismatch (30.0% vs. 67.5%; p = 0.001), and low flow (46.2% vs.
      72.5%; p = 0.02), but more frequent aortic regurgitation (87.5% vs. 20.0%; p <
      0.001). The presence of prosthesis-patient mismatch was independently associated
      with a low-flow state at discharge (odds ratio: 4.70; p = 0.004) and
      independently associated with the use of the sutureless prosthesis (odds ratio:
      3.90; p = 0.02). However, the survival of the 2 groups was comparable after 1.5
      year (interquartile range: 0.79 to 2.01 years) follow-up (log-rank test, p =
      0.95). CONCLUSIONS: TAVR prostheses demonstrated better hemodynamics than the 3f
      Enable valve but a higher incidence of aortic regurgitation. However, these
      differences did not influence mid-term survival of patients.

PMID- 25946437
TI  - European experience with the second-generation Edwards SAPIEN XT transcatheter
      heart valve in patients with severe aortic stenosis: 1-year outcomes from the
      SOURCE XT Registry.
AB  - OBJECTIVES: The SOURCE XT Registry (Edwards SAPIEN XT Aortic Bioprosthesis Multi
      Region Outcome Registry) assessed the use and clinical outcomes with the SAPIEN
      XT (Edwards Lifesciences, Irvine, California) valve in the real-world setting.
      BACKGROUND: Transcatheter aortic valve replacement is an established treatment
      for high-risk/inoperable patients with severe aortic stenosis. The SAPIEN XT is a
      balloon-expandable valve with enhanced features allowing delivery via a lower
      profile sheath. METHODS: The SOURCE XT Registry is a prospective, multicenter,
      post-approval study. Data from 2,688 patients at 99 sites were analyzed. The main
      outcome measures were all-cause mortality, stroke, major vascular complications,
      bleeding, and pacemaker implantations at 30-days and 1 year post-procedure.
      RESULTS: The mean age was 81.4 +/- 6.6 years, 42.3% were male, and the mean
      logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) was
      20.4 +/- 12.4%. Patients had a high burden of coronary disease (44.2%), diabetes
      (29.4%), renal insufficiency (28.9%), atrial fibrillation (25.6%), and peripheral
      vascular disease (21.2%). Survival was 93.7% at 30 days and 80.6% at 1 year. At
      30-day follow-up, the stroke rate was 3.6%, the rate of major vascular
      complications was 6.5%, the rate of life-threatening bleeding was 5.5%, the rate
      of new pacemakers was 9.5%, and the rate of moderate/severe paravalvular leak was
      5.5%. Multivariable analysis identified nontransfemoral approach (hazard ratio
      [HR]: 1.84; p < 0.0001), renal insufficiency (HR: 1.53; p < 0.0001), liver
      disease (HR: 1.67; p = 0.0453), moderate/severe tricuspid regurgitation (HR:
      1.47; p = 0.0019), porcelain aorta (HR: 1.47; p = 0.0352), and atrial
      fibrillation (HR: 1.41; p = 0.0014), with the highest HRs for 1-year mortality.
      Major vascular complications and major/life-threatening bleeding were the most
      frequently seen complications associated with a significant increase in 1-year
      mortality. CONCLUSIONS: The SOURCE XT Registry demonstrated appropriate use of
      the SAPIEN XT THV in the first year post-commercialization in Europe. The safety
      profile is sustained, and clinical benefits have been established in the real
      world setting. (SOURCE XT Registry; NCT01238497).

PMID- 25946439
TI  - The ever-increasing choices for aortic valve replacement: which one will win in
      the marketplace?

PMID- 25946440
TI  - Long-term outcomes of percutaneous paravalvular regurgitation closure after
      transcatheter aortic valve replacement: a multicenter experience.
AB  - OBJECTIVES: This study sought to evaluate acute and long-term outcomes of
      percutaneous paravalvular regurgitation (PVR) closure after transcatheter aortic
      valve replacement (TAVR). BACKGROUND: Severe symptomatic PVR is a predictor of
      all-cause mortality after TAVR. The current use of devices for transcatheter
      closure of PVR has been adapted from other indications without known long-term
      outcomes. METHODS: The study population consisted of a series of cases pooled
      together from an international multicenter experience. Patients underwent
      transcatheter implantation of a closure device for the treatment of clinically
      relevant PVR after TAVR with balloon-expandable or self-expandable prostheses.
      Procedural success was defined by successful deployment of a device with
      immediate reduction of PVR to a final grade <=2 as assessed by echocardiography.
      RESULTS: Twenty-seven procedures were performed in 24 patients with clinically
      relevant PVR after the index TAVR procedure (54.2% Edwards Sapien [Edwards
      Lifesciences, Irvine, California], 45.8% CoreValve [Medtronic, Minneapolis,
      Minnesota]). The study population included 75% men with a mean age of 80.6 +/-
      7.1 years and mean Society of Thoracic Surgeon score of 6.6%. The most frequently
      used device was Amplatzer Vascular Plug (St. Jude Medical, St. Paul, Minnesota)
      in 80% of the cases. Overall, 88.9% (24 of 27) of the procedures were technically
      successful and the results assessed by echocardiography were durable. However,
      cumulative survival rates at 1, 6, and 12 months were 83.3%, 66.7%, and 61.5%.
      Most of the deaths (8 of 11) were due to noncardiac causes. CONCLUSIONS:
      Transcatheter closure of PVR after TAVR can be performed with a high procedural
      success rate; however, the long-term mortality remains high mainly due to
      noncardiac causes.

PMID- 25946441
TI  - Plugging paravalvular leaks after transcatheter aortic valve replacement: why and
      how?

PMID- 25946442
TI  - Treatment of acquired von Willebrand syndrome in aortic stenosis with
      transcatheter aortic valve replacement.
AB  - OBJECTIVES: This study sought to investigate the prevalence of abnormal von
      Willebrand multimers (AbM) in patients undergoing transcatheter aortic valve
      replacement (TAVR) and the impact of TAVR on the underlying factor variances.
      BACKGROUND: An association between the acquired von Willebrand syndrome (aVWS)
      and valvular aortic stenosis (AS) has been established in the past and surgical
      aortic valve replacement (SAVR) shown to lead to factor recovery. Prevalence and
      course of AbM in patients treated with TAVR though has not yet been described
      comprehensively. METHODS: Ninety-five consecutive patients underwent TAVR at our
      institution. Hemostaseologic testing was performed before and up to 1 week after
      TAVR. Transvalvular and right heart hemodynamics as well as bleeding episodes
      were recorded and analyzed with descriptive statistics. RESULTS: Baseline
      prevalence of AbM was 42% with an average high-molecular-weight multimer (HMWM)
      count of 16.2 +/- 3.3%. Pressure gradients correlated significantly with the
      extent of HMWM deficiency (r = -0.63 [p < 0.0001]). Following valve implantation,
      HMWM increased proportional to the drop in mean pressure gradient and normalized
      in most of the patients. However, residual aortic regurgitation/leakage led to
      inferior HMWM recovery but prosthesis-patient mismatch (PPM) was rare and left
      HMWM uninfluenced. We saw no association of transfusion with AbM and 1-year
      mortality was unaffected by AbM. CONCLUSIONS: AbM in patients with AS undergoing
      TAVR is frequent. However, TAVR is capable of correcting AbM and therefore
      possibly aVWS in patients with AS. As opposed to SAVR, bleeding and transfusion
      requirement in TAVR patients was not associated with severe HMWM deficiency; PPM
      was rare and HMWM were uninfluenced by the procedure. Aortic regurgitation after
      TAVR adversely influenced HMWM recovery.

PMID- 25946443
TI  - Bleeding in patients with severe aortic stenosis in the era of transcatheter
      aortic valve replacement.

PMID- 25946444
TI  - Clinical outcomes and revascularization strategies in patients with low-flow, low
      gradient severe aortic valve stenosis according to the assigned treatment
      modality.
AB  - OBJECTIVES: This study compared clinical outcomes and revascularization
      strategies among patients presenting with low ejection fraction, low-gradient
      (LEF-LG) severe aortic stenosis (AS) according to the assigned treatment
      modality. BACKGROUND: The optimal treatment modality for patients with LEF-LG
      severe AS and concomitant coronary artery disease (CAD) requiring
      revascularization is unknown. METHODS: Of 1,551 patients, 204 with LEF-LG severe
      AS (aortic valve area <1.0 cm(2), ejection fraction <50%, and mean gradient <40
      mm Hg) were allocated to medical therapy (MT) (n = 44), surgical aortic valve
      replacement (SAVR) (n = 52), or transcatheter aortic valve replacement (TAVR) (n
      = 108). CAD complexity was assessed using the SYNTAX score (SS) in 187 of 204
      patients (92%). The primary endpoint was mortality at 1 year. RESULTS: LEF-LG
      severe AS patients undergoing SAVR were more likely to undergo complete
      revascularization (17 of 52, 35%) compared with TAVR (8 of 108, 8%) and MT (0 of
      44, 0%) patients (p < 0.001). Compared with MT, both SAVR (adjusted hazard ratio
      [adj HR]: 0.16; 95% confidence interval [CI]: 0.07 to 0.38; p < 0.001) and TAVR
      (adj HR: 0.30; 95% CI: 0.18 to 0.52; p < 0.001) improved survival at 1 year. In
      TAVR and SAVR patients, CAD severity was associated with higher rates of
      cardiovascular death (no CAD: 12.2% vs. low SS [0 to 22], 15.3% vs. high SS
      [>22], 31.5%; p = 0.037) at 1 year. Compared with no CAD/complete
      revascularization, TAVR and SAVR patients undergoing incomplete revascularization
      had significantly higher 1-year cardiovascular death rates (adj HR: 2.80; 95% CI:
      1.07 to 7.36; p = 0.037). CONCLUSIONS: Among LEF-LG severe AS patients, SAVR and
      TAVR improved survival compared with MT. CAD severity was associated with worse
      outcomes and incomplete revascularization predicted 1-year cardiovascular
      mortality among TAVR and SAVR patients.

PMID- 25946445
TI  - Incidence and predictors of debris embolizing to the brain during transcatheter
      aortic valve implantation.
AB  - OBJECTIVES: The aim of this study was to identify variables associated with
      tissue fragment embolization during transcatheter aortic valve replacement
      (TAVR). BACKGROUND: Brain magnetic resonance imaging and transcranial Doppler
      studies have revealed that cerebrovascular embolization occurs frequently during
      TAVR. Embolized material may be r thrombotic, tissue derived, or catheter
      (foreign material) fragments. METHODS: A total of 81 patients underwent TAVR with
      a dual filter-based embolic protection device (Montage Dual Filter System, Claret
      Medical, Inc., Santa Rosa, California) deployed in the brachiocephalic trunk and
      left common carotid artery. Both balloon-expandable and self-expanding
      transcatheter heart valves (THVs) were used. Filters were retrieved after TAVR
      and sent for histopathological analysis. RESULTS: Overall, debris was captured in
      86% of patients. Captured material varied in size from 0.1 to 9.0 mm. Thrombotic
      material was found in 74% of patients and tissue-derived debris in 63%. Tissue
      fragments were found more often with balloon-expandable THVs (79% vs. 56%; p =
      0.05). The embolized tissue originated from the native aortic valve leaflets,
      aortic wall, or left ventricular myocardium. On multivariable logistic regression
      analysis, balloon-expandable THVs (odds ratio: 7.315; 95% confidence interval:
      1.398 to 38.289; p = 0.018) and cover index (odds ratio: 1.141; 95% confidence
      interval: 1.014 to 1.283; p = 0.028) were independent predictors of tissue
      embolization. CONCLUSIONS: Debris is captured with filter-based embolic
      protection in the vast majority of patients undergoing TAVR. Tissue-derived
      material is found in 63% of cases and is more frequent with the use of balloon
      expandable systems and more oversizing.

PMID- 25946446
TI  - Filtering the truth behind cerebral embolization during transcatheter aortic
      valve replacement.

PMID- 25946447
TI  - Thrombus formation following transcatheter aortic valve replacement.
AB  - OBJECTIVES: This paper reviews the published data and reports 3 cases of
      thrombosis involving CoreValve (Medtronic, Minneapolis, Minnesota) and 1
      involving Edward Sapien (Edwards Lifesciences, Irvine, California) devices. Three
      of these cases had pathological findings at autopsy. BACKGROUND: Only a limited
      number of cases of valve dysfunction with rapid increase of transvalvular aortic
      gradients or aortic insufficiency post-transcatheter aortic valve replacement
      (TAVR) have been described. This nonstructural valvular dysfunction has been
      presumed to be because of early pannus formation or thrombosis. METHODS: Through
      reviews of the published reports and 4 clinical cases, pathological and clinical
      findings of early valve thrombosis are examined to elucidate methods for
      recognition and identifying potential causes and treatments. RESULTS: This paper
      presents 4 cases, 2 of which had increasing gradients post-TAVR. All 3 pathology
      cases showed presence of a valve thrombosis in at least 2 TAV leaflets on
      autopsy, but were not visualized by transthoracic echocardiogram or
      transesophageal echocardiogram. One case was medically treated with oral anti
      coagulation with normalization of gradients. The consequence of valve thrombosis
      in all 3 pathology patients either directly or indirectly played a role in their
      early demise. At least 18 case reports of early valve thrombosis have been
      published. In 12 of these cases, the early treatment with anticoagulation therapy
      resolved the thrombus formation and normalized aortic pressures gradients
      successfully. CONCLUSIONS: These 4 cases elucidate the occurrence of valve
      thrombosis post-TAVR. Consideration should be given to treatment with dual
      antiplatelet therapy and oral anticoagulation in patients post-TAVR with
      increasing mean pressure gradients and maximum aortic valve velocity. Further
      research should be conducted to create guidelines for antithrombotic therapy
      following TAVR procedure.

PMID- 25946448
TI  - Assessment of the geometric interaction between the Lotus transcatheter aortic
      valve prosthesis and the native ventricular aortic interface by 320-multidetector
      computed tomography.
AB  - OBJECTIVES: This study sought to assess the geometric interaction between the
      Lotus Valve System transcatheter aortic prosthesis (Boston Scientific, Natick,
      Massachusetts) and the native aortoventricular interface using multidetector
      computed tomography (MDCT). BACKGROUND: The interaction between transcatheter
      aortic valve prostheses and native anatomy is variable, although potentially
      predictable. The Lotus transcatheter device uses a novel mechanical means of
      expansion, the effect of which on native anatomic geometry has not previously
      been described. METHODS: Forty patients treated with the Lotus prosthesis were
      enrolled. The patients underwent 320-MDCT imaging before and after implantation.
      Prosthesis dimensions and relevant interaction parameters, including circularity
      and expansion, were assessed. The degree of paraprosthetic regurgitation (PAR)
      and prosthesis gradient were measured by transthoracic echocardiography at the
      same time points. RESULTS: The mean baseline annular eccentricity index (EI) was
      0.21 +/- 0.06 and left ventricular outflow tract EI was 0.31 +/- 0.09. The
      deployed prostheses had high rates of circularity with a mean EI across all
      device segments of 0.06 +/- 0.04. In noncircular device deployment, an EI >0.1
      was identified in 25% of prostheses and was associated with greater native
      annular eccentricity at baseline compared with circular devices (0.24 +/- 0.04
      vs. 0.19 +/- 0.06; p = 0.01). The median percent of expansion was 97.5 +/- 3.8%
      in the inflow portion of the prosthesis. Twenty-five percent of prostheses were
      <90% expanded in at least 1 segment with a numerical, but not statistically
      significant, association between oversizing and underexpansion. No correlation
      was found between device underexpansion and the mean transprosthesis gradient or
      between noncircularity and PAR. CONCLUSIONS: The Lotus prosthesis results in
      nearly full device expansion and circularization of the native basal plane.
      Awareness of the anatomic interaction between this unique device and the native
      architecture may help in the formulation of appropriate device-specific sizing
      algorithms.

PMID- 25946449
TI  - Percutaneous treatment of severe aortic insufficiency in a patient with left
      ventricular assist device: friend or foe.

PMID- 25946450
TI  - Bail-out technique for pulmonary artery rupture with a covered stent in balloon
      pulmonary angioplasty for chronic thromboembolic pulmonary hypertension.

PMID- 25946451
TI  - Transesophageal echocardiography-guided percutaneous intervention for a mitral
      valve leaflet perforation.

PMID- 25946452
TI  - Treatment strategies for prosthetic valve thrombosis-derived coronary embolism.

PMID- 25946453
TI  - Transcatheter left atrial appendage ligation therapy update.

PMID- 25946454
TI  - Innovation in intervention: transcatheter aortic valve replacement focus issue.

PMID- 25946455
TI  - Overestimation of paravalvular leak with Edwards SAPIEN 3 transcatheter aortic
      valve replacement.

PMID- 25946456
TI  - Double trouble: percutaneous disobstruction of 2 pulmonary veins following
      catheter ablation for atrial fibrillation.

PMID- 25946457
TI  - A man with 3 lives: long-term follow-up following percutaneous closure of left
      ventricular pseudoaneurysm neck.

PMID- 25946458
TI  - Percutaneous intervention to large left anterior descending artery fistula post
      right ventricular biopsy in a transplant recipient.

PMID- 25946460
TI  - Regulation of copper and iron homeostasis by metal chelators: a possible
      chemotherapy for Alzheimer's disease.
AB  - With the increase of life expectancy of humans in more than two-thirds of the
      countries in the World, aging diseases are becoming the frontline health
      problems. Alzheimer's disease (AD) is now one of the major challenges in drug
      discovery, since, with the exception of memantine in 2003, all clinical trials
      with drug candidates failed over the past decade. If we consider that the loss of
      neurons is due to a high level of oxidative stress produced by nonregulated redox
      active metal ions like copper linked to amyloids of different sizes, regulation
      of metal homeostasis is a key target. The difficulty for large copper-carrier
      proteins to directly extract copper ions from metalated amyloids might be
      considered as being at the origin of the rupture of the copper homeostasis
      regulation in AD brains. So, there is an urgent need for new specific metal
      chelators that should be able to regulate the homeostasis of metal ions,
      specially copper and iron, in AD brains. As a consequence of that concept,
      chelators promoting metal excretion from brain are not desired. One should favor
      ligands able to extract copper ions from sinks (amyloids being the major one) and
      to transfer these redox-active metal ions to copper-carrier proteins or copper
      containing enzymes. Obviously, the affinity of these chelators for the metal ion
      should not be a sufficient criterion, but the metal specificity and the ability
      of the chelators to release the metal under specific biological conditions should
      be considered. Such an approach is still largely unexplored. The requirements for
      the chelators are very high (ability to cross the brain-blood barrier, lack of
      toxicity, etc.), few chemical series were proposed, and, among them, biochemical
      or biological data are scarce. As a matter of fact, the bioinorganic pharmacology
      of AD represents less than 1% of all articles dedicated to AD drug research. The
      major part of these articles deals with an old and rather toxic drug, clioquinol
      and related analogs, that do not efficiently extract copper from soluble
      amyloids. We have designed and developed new tetradendate ligands such as 21 and
      PA1637 based on bis(8-aminoquinolines) that are specific for copper chelation and
      are able to extract copper(II) from amyloids and then can release copper ion upon
      reduction with a biological reducing agent. These studies contribute to the
      understanding of the physicochemical properties of the tetradentate copper
      ligands compared with bidentate ligands like clioquinol. One of these copper
      ligands, PA1637, after selection with a nontransgenic mouse model that is able to
      efficiently monitor the loss of episodic memory, is currently under preclinical
      development. 

PMID- 25946459
TI  - Essences in metabolic engineering of lignan biosynthesis.
AB  - Lignans are structurally and functionally diverse phytochemicals biosynthesized
      in diverse plant species and have received wide attentions as leading compounds
      of novel drugs for tumor treatment and healthy diets to reduce of the risks of
      lifestyle-related non-communicable diseases. However, the lineage-specific
      distribution and the low-amount of production in natural plants, some of which
      are endangered species, hinder the efficient and stable production of beneficial
      lignans. Accordingly, the development of new procedures for lignan production is
      of keen interest. Recent marked advances in the molecular and functional
      characterization of lignan biosynthetic enzymes and endogenous and exogenous
      factors for lignan biosynthesis have suggested new methods for the metabolic
      engineering of lignan biosynthesis cascades leading to the efficient,
      sustainable, and stable lignan production in plants, including plant cell/organ
      cultures. Optimization of light conditions, utilization of a wide range of
      elicitor treatments, and construction of transiently gene-transfected or
      transgenic lignan-biosynthesizing plants are mainly being attempted. This review
      will present the basic and latest knowledge regarding metabolic engineering of
      lignans based on their biosynthetic pathways and biological activities, and the
      perspectives in lignan production via metabolic engineering. 

PMID- 25946461
TI  - Oral Acyclovir and Intralesional Interferon Injections for Treatment of Giant
      Pyogenic Granuloma-Like Lesions in an Immunocompromised Patient With Human Orf.

PMID- 25946462
TI  - Bioengineered fibrin-based niche to direct outgrowth of circulating progenitors
      into neuron-like cells for potential use in cellular therapy.
AB  - OBJECTIVE: Autologous cells are considered to be the best choice for use in
      transplantation therapy. However, the challenges and risks associated with the
      harvest of transplantable autologous cells limit their successful therapeutic
      application. The current study explores the possibility of isolating neural
      progenitor cells from circulating multipotent adult progenitor cells for
      potential use in cell-based and patient-specific therapy for neurological
      diseases. APPROACH: To enable the selection of neural progenitor cells from human
      peripheral blood mononuclear cells, and to support their lineage maintenance, the
      composition of a fibrin-based niche was optimized. Morphological examination and
      specific marker analysis were carried out, employing a qualitative/quantitative
      polymerase chain reaction followed by immunocytochemistry to: (i) characterize
      neural progenitor cells in culture; (ii) monitor proliferation/survival; and
      (iii) track their differentiation status. MAIN RESULTS: The presence of neural
      progenitors in circulation was confirmed by the presence of nestin(+) cells at
      the commencement of the culture. The isolation, proliferation and differentiation
      of circulating neural progenitors to neuron-like cells were directed by the
      engineered niche. Neural cell isolation to near homogeneity was confirmed by the
      expression of beta-III tubulin in ~95% of cells, whereas microtubule associated
      protein-2 expression confirmed their ability to differentiate. The concentration
      of potassium chloride in the niche was found to favour neuron-like cell
      lengthening, cell-cell contact, and expressions of synaptophysin and tyrosine
      hydroxylase. SIGNIFICANCE: The purpose of this research was to find out if
      peripheral blood could serve as a potential source of neural progenitors for cell
      based therapy. The study established that neural progenitors could be selectively
      isolated from peripheral blood mononuclear cells using a biomimetic niche. The
      selected cells could multiply and slowly differentiate into neuron-like cells.
      These neuron-like cells expressed functional proteins-tyrosine hydroxylase and
      synaptophysin. Early progenitors that proliferate while expressing beta-III
      tubulin could be harvested from the culture, suggesting their potential use in
      cell transplantation therapy.

PMID- 25946463
TI  - Mitochondria DNA change and oxidative damage in clinically stable patients with
      major depressive disorder.
AB  - BACKGROUND: To compare alterations of mitochondria DNA (mtDNA) copy number,
      single nucleotide polymorphisms (SNPs), and oxidative damage of mtDNA in
      clinically stable patients with major depressive disorder (MDD). METHODS:
      Patients met DSM-IV diagnostic criteria for MDD were recruited from the
      psychiatric outpatient clinic at Changhua Christian Hospital, Taiwan. They were
      clinically stable and their medications had not changed for at least the
      preceding two months. Exclusion criteria were substance-induced psychotic
      disorder, eating disorder, anxiety disorder or illicit substance abuse.
      Comparison subjects did not have any major psychiatric disorder and they were
      medically healthy. Peripheral blood leukocytes were analyzed to compare copy
      number, SNPs and oxidative damage of mtDNA between the two groups. RESULTS: 40
      MDD patients and 70 comparison subjects were collected. The median age of the
      subjects was 42 years and 38 years in MDD and comparison groups, respectively.
      Leukocyte mtDNA copy number of MDD patients was significantly lower than that of
      the comparison group (p = 0.037). MDD patients had significantly higher
      mitochondrial oxidative damage than the comparison group (6.44 vs. 3.90,
      p<0.001). After generalized linear model adjusted for age, sex, smoking, family
      history, and psychotropic use, mtDNA copy number was still significantly lower in
      the MDD group (p<0.001). MtDNA oxidative damage was positively correlated with
      age (p<0.001) and MDD (p<0.001). Antipsychotic use was negatively associated with
      mtDNA copy number (p = 0.036). LIMITATIONS: The study is cross-sectional with no
      longitudinal follow up. The cohort is clinically stable and generalizability of
      our result to other cohort should be considered. CONCLUSIONS: Our study suggests
      that oxidative stress and mitochondria may play a role in the pathophysiology of
      MDD. More large-scale studies are warranted to assess the interplay between
      oxidative stress, mitochondria dysfunction and MDD.

PMID- 25946465
TI  - Lifestyle intervention using an internet-based curriculum with cell phone
      reminders for obese Chinese teens: a randomized controlled study.
AB  - OBJECTIVES: Obesity is an increasing public health problem affecting young
      people. The causes of obesity are multi-factorial among Chinese youth including
      lack of physical activity and poor eating habits. The use of an internet
      curriculum and cell phone reminders and texting may be an innovative means of
      increasing follow up and compliance with obese teens. The objectives of this
      study were to determine the feasibility of using an adapted internet curriculum
      and existing nutritional program along with cell phone follow up for obese
      Chinese teens. DESIGN AND METHODS: This was a randomized controlled study
      involving obese teens receiving care at a paediatric obesity clinic of a tertiary
      care hospital in Hong Kong. Forty-eight subjects aged 12 to 18 years were
      randomized into three groups. The control group received usual care visits with a
      physician in the obesity clinic every three months. The first intervention (IT)
      group received usual care visits every three months plus a 12-week internet-based
      curriculum with cell phone calls/texts reminders. The second intervention group
      received usual care visits every three months plus four nutritional counselling
      sessions. RESULTS: The use of the internet-based curriculum was shown to be
      feasible as evidenced by the high recruitment rate, internet log-in rate,
      compliance with completing the curriculum and responses to phone reminders. No
      significant differences in weight were found between IT, sLMP and control groups.
      CONCLUSION: An internet-based curriculum with cell phone reminders as a
      supplement to usual care of obesity is feasible. Further study is required to
      determine whether an internet plus text intervention can be both an effective and
      a cost-effective adjunct to changing weight in obese youth. TRIAL REGISTRATION:
      Chinese Clinical Trial Registry ChiCTR-TRC-12002624.

PMID- 25946467
TI  - Solar-Blind Avalanche Photodetector Based On Single ZnO-Ga2O3 Core-Shell
      Microwire.
AB  - High-performance solar-blind (200-280 nm) avalanche photodetectors (APDs) were
      fabricated based on highly crystallized ZnO-Ga2O3 core-shell microwires. The
      responsivity can reach up to 1.3 * 10(3) A/W under -6 V bias. Moreover, the
      corresponding detectivity was as high as 9.91 * 10(14) cm.Hz(1/2)/W. The device
      also showed a fast response, with a rise time shorter than 20 MUs and a decay
      time of 42 MUs. The quality of the detectors in solar-blind waveband is
      comparable to or even higher than that of commercial Si APD (APD120A2 from
      Thorlabs Inc.), with a responsivity ~8 A/W, detectivity ~10(12) cm.Hz(1/2)/W, and
      response time ~20 ns. The high performance of this APD make it highly suitable
      for practical applications as solar-blind photodetectors, and this core-shell
      microstructure heterojunction design method would provide a new approach for
      realizing an APD device.

PMID- 25946466
TI  - Child Support Conviction and Recidivism: A Statistical Interaction Pattern by
      Race.
AB  - An estimated 50,000 parents are behind bars on average daily for child support
      nonpayment, but information about these fathers and their recidivism rates are
      lacking. Using a jail sample (N = 16,382), multinomial logistics regression
      method was utilized; subgroup analysis was used to investigate differential beta
      weights of predictor variables. Informed by Critical Race Theory, findings showed
      that fathers incarcerated for arrears had significantly higher rates of
      recidivism than other jailed men, but had an interaction effect with race. After
      controlling for age, education, and prior attendance at 12-step meetings, Black
      fathers but NOT White fathers showed significant post-release recidivism.
      Implications are discussed. 

PMID- 25946464
TI  - Hybridization within Saccharomyces Genus Results in Homoeostasis and Phenotypic
      Novelty in Winemaking Conditions.
AB  - Despite its biotechnological interest, hybridization, which can result in hybrid
      vigor, has not commonly been studied or exploited in the yeast genus. From a
      diallel design including 55 intra- and interspecific hybrids between
      Saccharomyces cerevisiae and S. uvarum grown at two temperatures in enological
      conditions, we analyzed as many as 35 fermentation traits with original
      statistical and modeling tools. We first showed that, depending on the types of
      trait--kinetics parameters, life-history traits, enological parameters and aromas
      -, the sources of variation (strain, temperature and strain * temperature
      effects) differed in a large extent. Then we compared globally three groups of
      hybrids and their parents at two growth temperatures: intraspecific hybrids S.
      cerevisiae * S. cerevisiae, intraspecific hybrids S. uvarum * S. uvarum and
      interspecific hybrids S. cerevisiae * S. uvarum. We found that hybridization
      could generate multi-trait phenotypes with improved oenological performances and
      better homeostasis with respect to temperature. These results could explain why
      interspecific hybridization is so common in natural and domesticated yeast, and
      open the way to applications for wine-making.

PMID- 25946468
TI  - Transcriptome profiling identifies p53 as a key player during calreticulin
      deficiency: Implications in lipid accumulation.
AB  - Calreticulin (CRT) is an endoplasmic reticulum (ER) resident calcium binding
      protein that is involved in several cellular activities. Transcriptome analyses
      in CRT knockdown HepG2 cells revealed 253 altered unique genes and subsequent in
      silico protein-protein interaction network and MCODE clustering identified 34
      significant clusters, of which p53 occupied the central hub node in the highest
      node-rich cluster. Toward validation, we show that CRT knockdown leads to
      inhibition of p53 protein levels. Both, CRT and p53 siRNA promote hepatic lipid
      accumulation and this was accompanied by elevated SREBP-1c and FAS levels. p53
      was identified to bind at -219 bp on the SREBP-1c promoter and in the presence of
      CRT siRNA, there was decreased occupancy of p53 on this binding element. This was
      associated with increased SREBP-1c promoter activity and both, mutation in this
      binding site or p53 over-expression antagonised the effects of CRT knockdown. We,
      therefore, identify a negatively regulating p53 binding site on the SREBP-1c
      promoter that is critical during hepatic lipid accumulation. These results were
      validated in mouse primary hepatocytes and toward a physiological relevance, we
      report that while the levels of CRT and p53 are reduced in the fatty livers of
      diabetic db/db mice, SREBP-1c levels are significantly elevated. Our results
      suggest that decreased CRT levels might be involved in the development of a fatty
      liver by preventing p53 occupancy on the SREBP-1c promoter and thereby
      facilitating SREBP-1c up-regulation and consequently, lipid accumulation. 

PMID- 25946469
TI  - Clinical utility of plasma Epstein-Barr virus DNA and ERCC1 single nucleotide
      polymorphism in nasopharyngeal carcinoma.
AB  - BACKGROUND: Single nucleotide polymorphism (SNP) of the excision repair cross
      complementing group 1 (ERCC1) gene has been linked with sensitivity to platinum
      and radiation. The authors hypothesized that the ERCC1 genotype for the SNPs
      cytosine-to-thymine substitution at codon 118 (C118T) and cytosine-to-adenine
      substitution at codon 8092 (C8092A) is prognostic in patients with nasopharyngeal
      carcinoma (NPC) who receive either radiotherapy (RT) or cisplatin plus RT.
      METHODS: The authors tested their hypothesis using biomarker screening samples
      from the Hong Kong NPC Study Group 0502 trial, which was a prospective,
      multicenter clinical trial that used post-RT plasma Epstein-Bar virus (EBV) DNA
      (pEBV) levels to screen patients with high-risk NPC for adjuvant chemotherapy.
      RESULTS: ERCC1 SNPs were analyzed in 576 consecutive patients who were screened
      by pEBV. In the total biomarker population, there was no significant association
      of ERCC1 C118T or C8092A genotype with relapse-free survival (RFS) or overall
      survival (OS). There also was no correlation between ERCC1 genotype and ERCC1
      protein or messenger RNA expression in a subset of patients who had available
      paired biopsies. Post-RT pEBV status was the only independent prognosticator for
      RFS and OS in multivariate analyses. However, there was a significant interaction
      between ERCC1 C118T genotype and post-RT pEBV status (RFS, P = .0106; OS, P =
      .0067). The ERCC1 C118T genotype was significantly associated with both RFS
      (hazard ratio, 1.67; 95% confidence interval, 1.07-2.61; P = .024) and OS (hazard
      ratio, 2.31; 95% confidence interval, 1.22-4.40; P = .0106) in the post-RT pEBV
      negative population, but not in the pEBV-positive population. CONCLUSIONS: The
      current results prospectively validate pEBV as the most significant prognostic
      biomarker in NPC that can be used to select high-risk patients for adjuvant
      therapy. The ERCC1 C118T genotype may help to identify a favorable subgroup
      (approximately 7%) of pEBV-negative patients with NPC who have an excellent
      prognosis and can be spared the toxicities of further therapy.

PMID- 25946471
TI  - Medium-Term Recurrence and Quality of Life Assessment Using the Hernia-Specific
      Carolinas Comfort Scale Following Laparoscopic Inguinal Hernia Repair.
AB  - OBJECTIVES: To determine the long-term outcomes and quality of life (QoL)
      following laparoscopic mesh repair of inguinal hernias using the hernia-specific
      Carolinas Comfort Scale((r)) (CCS) questionnaire (Carolinas Laparoscopic and
      Advanced Surgery Program, Carolinas HealthCare System, Charlotte, NC). MATERIALS
      AND METHODS: All patients who underwent elective primary or recurrent
      laparoscopic transabdominal preperitoneal (TAPP) inguinal hernia repair from
      January 2005 to May 2010 were identified from a prospectively maintained clinical
      database. Baseline patient characteristics were recorded, including occupation,
      in addition to mean operating time, hernia recurrence rates, and postoperative
      CSS. RESULTS: Four hundred fifty-nine patients underwent surgery during the study
      period. The median follow-up interval from the date of operation to the date the
      questionnaire sent was 23 months (interquartile range, 32 months), and the total
      number of valid responses was 250. The median age of patients was 58 years
      (interquartile range, 21 years). The median operating time was 42 minutes
      (interquartile range, 21 minutes). Thirty-five patients (15%) and 15 patients
      (12%) had bilateral and recurrent hernia repairs, respectively. Three patients
      (1.1%) were confirmed to have hernia recurrence. Analysis of the CSS scores
      revealed that 41 patients (16%) reported pain, 44 (18%) reported mesh sensation,
      and 25 (10%) reported movement limitation. However, severe or disabling mesh
      related symptoms were present in 5 patients (2%) for the pain category, in 8
      patients (3%) for the mesh sensation category, and in 9 patients (3%) for the
      movement limitation symptom. The number of patients who were completely
      asymptomatic in all three symptom categories was 190 (24%). The only significant
      risk factor for developing mesh-related symptoms was young age at the time of
      surgery. CONCLUSIONS: Patient-reported medium-term symptoms following
      laparoscopic inguinal hernia repair appear common; however, the prevalence of
      severe or disabling symptoms is low.

PMID- 25946472
TI  - Evaluation of chlorpyrifos transferred from contaminated feed to duck commodities
      and dietary risks to Chinese consumers.
AB  - The present study describes chlorpyrifos residues in duck commodities through the
      duck food chain, transfer factors, and dietary risks to Chinese consumers. After
      duck feeding experiments with pellet feed that lasted for 42 days, chlorpyrifos
      residues found in all samples collected from the ducks on maximum estimated dose
      group (3.20 mg/kg level) were from <0.0005 to 0.019 mg/kg. The residue levels of
      the fat, intestine, and tongue were obviously higher than those of the meat and
      other edible tissues. The transfer factors of all duck commodities were from
      0.0001 to 0.0049 among different contamination levels, which indicated that
      chlorpyrifos had a low persistency in duck meat and metabolism organs. The
      chronic exposure assessment revealed that only 0.034-0.150% of the acceptable
      daily intake (ADI; 0-0.01 mg/kg/bw/day) of chlorpyrifos was consumed via the duck
      commodities for different age and gender groups in China. The acute exposure
      assessments of different age and gender groups were only 0.019-0.082% of the
      acute reference dose (ARfD; 0-0.1 mg/kg/bw). The results show that the single
      dietary exposure risk of chlorpyrifos raised by the intake of duck commodities
      was quite low in China. 

PMID- 25946470
TI  - Quantitative trait loci associated with constitutive traits control water use in
      pearl millet [Pennisetum glaucum (L.) R. Br].
AB  - There is substantial genetic variation for drought adaption in pearl millet in
      terms of traits controlling plant water use. It is important to understand
      genomic regions responsible for these traits. Here, F7 recombinant inbred lines
      were used to identify quantitative trait loci (QTL) and allelic interactions for
      traits affecting plant water use, and their relevance is discussed for crop
      productivity in water-limited environments. Four QTL contributed to increased
      transpiration rate under high vapour pressure deficit (VPD) conditions, all with
      alleles from drought-sensitive parent ICMB 841. Of these four QTL, a major QTL
      (35.7%) was mapped on linkage group (LG) 6. The alleles for 863B at this QTL
      decreased transpiration rate and this QTL co-mapped to a previously detected LG 6
      QTL, with alleles from 863B for grain weight and panicle harvest index across
      severe terminal drought stress environments. This provided additional support for
      a link between water saving from a lower transpiration rate under high VPD and
      drought tolerance. 863B alleles in this same genomic region also increased shoot
      weight, leaf area and total transpiration under well-watered conditions. One
      unexpected outcome was reduced transpiration under high VPD (15%) from the
      interaction of two alleles for high VPD transpiration (LG 6 (B), 40.7) and
      specific leaf mass and biomass (LG 7 (A), 35.3), (A, allele from ICMB 841, B,
      allele from 863B, marker position). The LG 6 QTL appears to combine alleles for
      growth potential, beneficial for non-stress conditions, and for saving water
      under high evaporative demand, beneficial under stressful conditions. Mapping QTL
      for water-use traits, and assessing their interactions offers considerable
      potential for improving pearl millet adaptation to specific stress conditions
      through physiology-informed marker-assisted selection.

PMID- 25946473
TI  - Magnetic Fields Facilitate DNA-Mediated Charge Transport.
AB  - Exaggerated radical-induced DNA damage under magnetic fields is of great concern
      to medical biosafety and biomolecular electronic devices. In this report, the
      effects of an external magnetic field (MF) on DNA electronic conductivity were
      investigated by studying the efficiencies of photoinduced DNA-mediated charge
      transport (CT) via guanine damage. Under a static MF of 300 mT, positive
      enhancements in the decomposition of 8-cyclopropyldeoxyguanosine ((8CP)G) were
      observed at both the proximal and distal guanine doublets, indicating a more
      efficient propagation of radical cations and higher electronic conductivity of
      duplex DNA. MF-assisted CT has shown sensitivity to magnetic field strength,
      duplex structures, and the integrity of base pair stacking. Spin evolution of
      charge injection and the alignment of base pairs to the CT-active conformation
      during radical propagation were proposed to be the two major factors that MF
      contributes to facilitate DNA-mediated CT. Herein, MF-assisted CT may offer a new
      avenue for designing DNA-based electronic devices and unraveling MF effects on
      redox and radical relevant biological processes. 

PMID- 25946474
TI  - Cardiorespiratory Fitness of High Altitude Mountaineers: The Underestimated
      Prerequisite.

PMID- 25946475
TI  - Insufflation using carbon dioxide versus room air during colonoscopy: comparison
      of patient comfort, recovery time, and nursing resources.
AB  - The standard of practice for colonoscopy is room air insufflation. Recent
      research demonstrates safety and significant decrease in postcolonoscopy
      discomfort from distention when carbon dioxide (CO2) is used during insufflation.
      Reducing abdominal pain after colonoscopy may lead to increased acceptance of
      colonoscopy screening for colorectal cancer. This study aims to compare patient
      comfort intra- and postprocedure, length of recovery, and nursing time in
      patients undergoing colonoscopy using room air vs. CO2 insufflation. This study
      uses an experimental design with patients randomly assigned to either room air or
      CO2 during colonoscopy. Physician endoscopists, postprocedure nurses, and
      patients were blinded to assignment. Prior bowel surgery, inflammatory bowel
      disease, or inability to consent excluded participants. Outcome measures included
      discomfort assessment, nursing tasks, and recovery time.Of 191 participants, 177
      were men and 14 were women; 94 received room air; 97 received CO2. Patients
      insufflated with room air reported higher levels of some measures of discomfort:
      (a) during colonoscopy (p = .02), (b) on admission to recovery (p = .001), and
      (c) on discharge from recovery (p = .001). Patients receiving room air required
      more nursing tasks in recovery (p = .001) and more total nursing time (p =
      .001).Compared with room air, CO2 insufflation increases patient comfort and
      decreases nursing tasks and time. 

PMID- 25946476
TI  - Performance of different categories of operators in simulated diagnostic
      colonoscopy.
AB  - The possible involvement, although limited to the diagnostic phase of the
      procedure, of nonmedical staff (particularly endoscopy nurses) in lower digestive
      endoscopy has recently been suggested. Computer-based simulators have
      demonstrated objective evaluation of technical skills in digestive endoscopy. The
      aim of this study was to evaluate basic colonoscopy skills of endoscopy nurses
      (naive operators), as compared with junior physician staff and senior
      endoscopists, through a virtual reality colonoscopy simulator. In this single
      center, prospective, nonrandomized study, 3 groups of digestive endoscopy
      operators (endoscopy nurses, junior doctors [<150 previous colonoscopies], expert
      doctors [>500 previous colonoscopies and >200/year]) completed six diagnostic
      cases generated by an endoscopic simulator (AccuTouch, Immersion Medical,
      Gaithersburg, MD). The performance parameters, collected by the simulator, were
      compared between groups. Five parameters have been considered for statistical
      analysis: time spent to reach the cecum; pain of any degree; severe/extreme pain;
      amount of insufflated air; percentage of visualized mucosa. Statistical analysis
      to compare the three groups has been performed by means of Wilcoxon test for two
      independent samples and by means of Kruskal-Wallis test for three independent
      samples (p < .05). Sixteen operators have been studied (six endoscopy nurses,
      five junior doctors, and five senior doctors); 96 colonoscopic procedures have
      been evaluated. Statistically significant differences between experts and naive
      operators were observed regarding time to reach the cecum and induction of
      severe/extreme pain, with both Kruskal-Wallis and Wilcoxon test (p < .05); all
      other comparisons did not reach statistical significance. Although, as expected,
      expert doctors exceeded both junior doctors and naive operators in some relevant
      quality parameters of simulated diagnostic colonoscopies, the results obtained by
      less expert performers--and particularly by nursing staff--appear satisfactory as
      in regards to most of the considered quality parameters and suggest a potential
      value of this device in effectively teaching basic lower digestive endoscopy to
      beginners in a relatively short time.

PMID- 25946477
TI  - Injectable drug supply disruption update: neuromuscular block reversal drugs.

PMID- 25946478
TI  - Breaking the mold: creating greatness.

PMID- 25946479
TI  - Assessment of the Turkish Version of the King's Stool Chart for Evaluating Stool
      Output and Diarrhea Among Patients Receiving Enteral Nutrition.
AB  - The purpose of this study was to evaluate the reliability and validity of the
      Turkish version of the King's Stool Chart (KSC-Tr) in patients receiving enteral
      nutrition. In total, 212 stool samples taken from 25 patients receiving enteral
      nutrition during 393 sick days in two intensive care units were assessed using
      the KSC-Tr. Overall, 110 of 212 stools (51.9%) were characterized as liquid and
      111 of 212 stools (52.4%) were characterized as less than 100 g. The daily stool
      score of patients receiving antibiotics, a risk factor for diarrhea, was higher
      (mean = 13.6; SD = 10.1) than that of patients not receiving antibiotics (mean =
      9.3; SD = 5.0) (p = .001). Diarrhea occurred on more days when patients received
      antibiotics (62/329; 18.8%) than on days when they did not (3/64; 4.7%) (p =
      .005). Interobserver agreement of two independent nurses' assessments on 44 stool
      samples was examined and was good for both stool consistency (kappa = 0.76) and
      stool weight (kappa = 0.75). In the intensive care unit, the KSC-Tr can be used
      as a valid and reliable tool for monitoring diarrhea and stool output in patients
      receiving enteral nutrition.

PMID- 25946480
TI  - A Clinical Trial to Detect Subclinical Transfusion-induced Lung Injury during
      Surgery.
AB  - BACKGROUND: Transfusion-related acute lung injury incidence remains the leading
      cause of posttransfusion mortality. The etiology may be related to leukocyte
      antibodies or biologically active compounds in transfused plasma, injuring
      susceptible recipient's lungs. The authors have hypothesized that transfusion
      could have less severe effects that are not always appreciated clinically and
      have shown subtly decreased pulmonary oxygen gas transfer in healthy volunteers
      after transfusion of fresh and 21-day stored erythrocytes. In this study, the
      authors tested the same hypothesis in surgical patients. METHODS: Ninety-one
      patients undergoing elective major spine surgery with anticipated need for
      erythrocyte transfusion were randomly allocated to receive their first
      transfusion of erythrocytes as cell salvage (CS), washed stored, or unwashed
      stored. Clinicians were not blinded to group assignment. Pulmonary gas transfer
      and mechanics were measured 5 min before and 30 min after erythrocyte
      transfusion. RESULTS: The primary outcome variable, gas transfer, as assessed by
      change of PaO2/FIO2, with erythrocyte transfusion was not significant in any
      group (mean +/- SD; CS: 9 +/- 59; washed: 10 +/- 26; and unwashed: 15 +/- 1) and
      did not differ among groups (P = 0.92). Pulmonary dead space (VD/VT) decreased
      with CS transfusion (-0.01 +/- 0.04; P = 0.034) but did not change with other
      erythrocytes; the change from before to after erythrocyte transfusion did not
      differ among groups (-0.01 to +0.01; P = 0.28). CONCLUSIONS: The authors did not
      find impaired gas exchange as assessed by PaO2/FIO2 with transfused erythrocytes
      that did or did not contain nonautologous plasma. This clinical trial did not
      support the hypothesis of erythrocyte transfusion-induced gas exchange deficit
      that had been found in healthy volunteers.

PMID- 25946481
TI  - Evaluation of agro-industrial wastes, their state, and mixing ratio for maximum
      polygalacturonase and biomass production in submerged fermentation.
AB  - The potential of important agro-industrial wastes, apple pomace (AP) and orange
      peel (OP) as C sources, was investigated in the maximization of polygalacturonase
      (PG), an industrially significant enzyme, using an industrially important
      microorganism Aspergillus sojae. Factors such as various hydrolysis forms of the
      C sources (hydrolysed-AP, non-hydrolysed-AP, hydrolysed-AP + OP, non-hydrolysed
      AP + OP) and N sources (ammonium sulphate and urea), and incubation time (4, 6,
      and 8 days) were screened. It was observed that maximum PG activity was achieved
      at a combination of non-hydrolysed-AP + OP and ammonium sulphate with eight days
      of incubation. For the pre-optimization study, ammonium sulphate concentration
      and the mixing ratios of AP + OP at different total C concentrations (9, 15, 21 g
      l(-1)) were evaluated. The optimum conditions for the maximum PG production
      (144.96 U ml(-1)) was found as 21 g l(-1) total carbohydrate concentration
      totally coming from OP at 15 g l(-1) ammonium sulphate concentration. On the
      other hand, 3:1 mixing ratio of OP + AP at 11.50 g l(-1) ammonium sulphate
      concentration also resulted in a considerable PG activity (115.73 U ml(-1)).
      These results demonstrated that AP can be evaluated as an additional C source to
      OP for PG production, which in turn both can be alternative solutions for the
      elimination of the waste accumulation in the food industry with economical
      returns.

PMID- 25946482
TI  - Sequential bilateral cochlear implantation in the adolescent population.
AB  - OBJECTIVES: To examine the variables affecting outcomes for sequential bilateral
      cochlear implantation patients in the adolescent population. STUDY DESIGN:
      Retrospective chart review at tertiary care center. METHODS: Main outcome
      measures were open set speech recognition tests at the word (Consonant-Nucleus
      Consonant/Phonetically Balanced Kindergarten List Test [CNC/PBK]) and sentence
      levels in noise (Hearing in Noise Test-Noise [HINT-N]) in different test
      conditions with respect to the age at first and sequential implantation, as well
      as the interval between implants. RESULTS: Despite a mean age at sequential
      implantation of 13.5 years, sequential bilateral implanted adolescents revealed
      significant improvement in the sequential cochlear implant (CI2) ear. The mean
      time interval between implants was 8.2 years. A wide range of performance was
      noted, and age at implantation and interval between first cochlear implant (CI1)
      and CI2 did not predict outcome. Mean CNC/PBK score with CI1 alone was 83.0%,
      with the CI2 alone was 56.5%, and with bilateral implants was 86.8%. Sentence
      scores (HINT-N) were 89.5% for CI1, 74.2% for CI2, and 94.4% for bilateral CI
      condition. The clinical relevance of these enhanced perception abilities requires
      attention to individual device use, performance with the first implant, and
      subjective benefits reported by patients. CONCLUSIONS: Bilateral sequential
      cochlear implantation leads to improved speech perception in the adolescent
      population and should be considered in this population, even after a long period
      of deafness and despite a prolonged interval between implants. Numerous factors
      affect the ability to predict performance, but age at implantation and
      interimplant interval were not correlated with performance measures. Extensive
      preoperative counseling and individualized evaluation are critical to ensure that
      patients and families understand the range of possible outcomes. LEVEL OF
      EVIDENCE: 4

PMID- 25946483
TI  - Prognostic relevance of apparent diffusion coefficient obtained by diffusion
      weighted MRI in pancreatic cancer.
AB  - BACKGROUND: Diffusion-weighted magnetic resonance imaging (DW-MRI) is utilized as
      a method of oncologic imaging for predicting treatment outcomes. This study
      explored the role of DW-MRI in the treatment of patients with resected pancreatic
      cancer by comparing apparent diffusion coefficient (ADC) values with
      clinicopathological findings and survival rates. MATERIALS AND METHODS: Records
      of 54 patients in whom DW-MRI at 1.5T was performed (b values: 0 and 1000 mm(2)
      /s) before macroscopically curative resection were analyzed. ADC values were then
      calculated and compared with clinicopathological factors including age, gender,
      serum carcinoembryonic antigen levels, serum carbohydrate antigen 19-9 levels,
      lymph node metastasis, primary tumoral location, size, differentiation,
      resectability, and pT stage. A survival analysis of clinicopathological factors
      and ADC values was performed using the Kaplan-Meier method, and the results were
      evaluated with the log-rank test. Prognostic significance was assessed using the
      Cox proportional hazard model. RESULTS: Significant associations were found
      between tumor differentiation and ADC values (P = 0.001). In a univariate
      analysis of overall survival, tumor differentiation (P = 0.037) and ADC values (P
      = 0.002) were identified as significant prognostic factors. However, age, gender,
      carcinoembryonic antigen levels, carbohydrate antigen 19-9 levels, lymph node
      metastasis, primary tumoral location, size, resectability, and pT stage were not
      associated with overall survival. In a multivariate analysis of overall survival,
      only ADC values were identified as significant prognostic factors (hazard ratio
      2.293, 95% confidence interval 1.147-4.585, P = 0.019). CONCLUSION: ADC values
      were found to be associated with prognosis in patients with resected pancreatic
      cancer.

PMID- 25946484
TI  - What is your diagnosis? Ulcerative nasal lesion in a Quarter Horse.

PMID- 25946485
TI  - Piriform aperture enlargement for nasal obstruction.

PMID- 25946486
TI  - The Nrf2-ARE pathway is associated with Schisandrin b attenuating benzo(a)pyrene
      Induced HTR cells damages in vitro.
AB  - As is ubiquitous in the environmental sources, benzo(a)pyrene (BaP) has been
      reported to induce reprotoxicity in previous studies. Toxicity to trophoblast
      cells may be one key factor, but evidences were absent. We speculated that BaP
      can induce cytotoxicity in human trophoblast HTR-8/SVneo (HTR) cells, and
      Schisandrin B (Sch B) as a potential protector can inhibit the cytotoxicity. MTS
      assay identified that BaP induced HTR cells death while Sch B played a
      cytoprotective role. And after Nrf2 interference, the ability of Sch B-induced
      cytoprotection was declined. Furthermore, PCR, western blot, ELISA, and SOD
      assays were found that Sch B significantly increased the mRNA and protein
      expression of Nrf2, HO1, NQO1, and SOD in the Nrf2-ARE pathway, and the extents
      of increase were declined after Nrf2 interference. These results demonstrated
      that the Nrf2-ARE pathway plays an important role in Sch B attenuating BaP
      induced HTR cells damages in vitro. (c) 2015 Wiley Periodicals, Inc. Environ
      Toxicol 31: 1439-1449, 2016.

PMID- 25946487
TI  - Influence of surface functionalization on the hydrophilic character of mesoporous
      silica nanoparticles.
AB  - We report the synthesis and surface functionalization of MCM-41-like mesoporous
      silica nanoparticles (MSNs) with spheroidal shape and particle size of 141 +/- 41
      nm. The success of surface functionalization with aminopropyl and sodium
      ethylcarboxylate groups (giving amino-MSN and carboxy-MSN, respectively) was
      ascertained by infrared spectroscopy and zeta potential measurements. The former
      showed the decrease of surface silanol groups and the corresponding appearance of
      signals related to NH2 bending mode (deltaNH2) at 1595 cm(-1) and COO(-)
      stretching (nuas and nusym) at 1562 and 1418 cm(-1). The latter showed a change
      in surface charge, in that the isoelectric point (IEP) changed from pH 3-4.5 to
      8.5 when the MSN was functionalized with the amino groups, while carboxy-MSN
      showed a more negative charge in the whole pH range with respect to MSN. The
      hydrophilic character of the prepared materials was ascertained by quantitative
      microgravimetric measurements, allowing the calculation of the average isosteric
      adsorption heat (q[combining macron]st). This was found to be 51 +/- 3 kJ mol(
      1), 61 +/- 4, and 65 +/- 3 kJ mol(-1) for MSN, amino-MSN, and carboxy-MSN
      samples, respectively. The increase in q[combining macron]st after
      functionalization can be ascribed to the specific interaction of water molecules
      with the functionalizing agents, in agreement with a higher basicity with respect
      to silanol groups. Moreover, the possibility of multiple H-bonding interactions
      of water molecules with the carboxylate anion is put forward to account for the
      higher water uptake with respect to parent MSN. 

PMID- 25946488
TI  - Challenges beyond the scientific knowledge production.

PMID- 25946489
TI  - Serious game e-Baby: nursing students' perception on learning about preterm
      newborn clinical assessment.
AB  - OBJECTIVE: To evaluate students opinion regarding e-Baby educational technology.
      METHODOLOGY: Exploratory descriptive study in which participated a sample
      composed of 14 nursing Portuguese students that used e-Baby digital educational
      technology in an extracurricular course. To achieve the aim of the study, the
      data collection was realized through an opinion instrument in Likert scale
      including the possibility of commentaries by students. Is was also collected data
      of participants' characterization. RESULTS: Students made very satisfactory
      evaluations regarding the game e-Baby, varying since usability acceptation
      through suggestions of expansion of the game to other nursing themes. CONCLUSION:
      Serious game e-Baby can be considered a didactic innovation and motivator tool of
      learning. Besides, it demonstrates have adequate interface in design and
      educative function aspects, evocating intense interaction between user and
      computational tool.

PMID- 25946490
TI  - Learning needs of Nursing students in technical vocational education.
AB  - OBJECTIVE: Identify learning needs of students of Technical Vocational Education
      (TVE) in Nursing. Qualitative study conducted in a city of Sao Paulo state.
      METHOD: The subjects were students, teachers and coordinators of TVE and students
      of the bachelor degree who have had contact with TVE. Data collection was
      performed by questionnaire socioeconomic and cultural circles about the learning
      needs. For data analysis we used the content analysis. RESULTS: It was found that
      students have difficulties contents not related to nursing as portuguese and
      mathematics, as well as introductory courses in the course of TVE which possibly
      may interfere negatively in learning specific content of nursing and the quality
      of health care. CONCLUSION: It is necessary to rethink the content taught and
      ways to teach from basic education, as well as the training of teachers who now
      works in the TVE.

PMID- 25946492
TI  - Knowing blood donation surroundings: Implications for nurse service in
      hemotherapy.
AB  - OBJECTIVE: The study aims at discussing the significations apprehended by the non
      blood donators, considering the context and the consequences of the acting of the
      nurse in hemotherapy. METHOD: It is a qualitative approach, with theoretical
      frame of Symbolic Interactionism and Grounded Theory method. The data production
      was carried out by intensive interview with subjects of three sample groups of a
      University Hospital of Rio de Janeiro City. RESULTS: The phenomenon originated
      two analysis categories: "Perceiving the blood matter" and "Reflecting about the
      blood donation campaigns". It was observed that the environment of the donor is
      not composed by contact with the other and the information that it can achieve,
      including the media. CONCLUSION: These were the main basis for the knowledge of
      blood donation according to their beliefs, culture and values. Therefore, all
      these aspects must be considered by the nurse acting on donors capture.

PMID- 25946491
TI  - Quality of life and physical activity in intensive care professionals from middle
      Sao Francisco.
AB  - OBJECTIVE: The objective was to assess the level of physical activity (LPA) and
      the quality of life QL of the professionals who work in ICU. METHOD: This was a
      cross-sectional study carried out in Adult ICUs. LPA was assessed by the
      International Questionnarie of Physical Activity--short form (IQPA-SF) and the QL
      by the Medical Outcomes Study 36 (SF-36) questionnaire. RESULTS: It was
      classified active 50.89% out of a total of 59 professionals. Nursing technicians
      were considered the most active with 60.6%. The QL of the professionals who were
      considered active were better when compared to inactives, with statistical
      differences to the category of physical aspects limitation, social aspects and
      mental health. The working hours were higher than recommend, the physicians were
      higher than the physical therapist, nurses and technicians nurses (p = 0.046).
      CONCLUSION: Physically active professionals who work in ICU had higher quality of
      life probably why have lower hours of work and consequently more free time to
      engage in physical activity.

PMID- 25946493
TI  - Entrepreneurship in Nursing: overview of companies in the State of Sao Paulo.
AB  - OBJECTIVE: The present study aimed to identify and characterize nursing companies
      managed by entrepreneur nurses registered at the Commercial Registry of Sao Paulo
      by 2011. METHOD: It's a descriptive, exploratory study, whose data collection,
      made throughout January 2012, was carried out on the Commercial Registry of Sao
      Paulo website. This non-governmental body has the function of registering the
      opening of companies and supervising their trade situation. RESULTS AND
      CONCLUSION: This study allowed us to identify that the entrepreneur nurse is a
      growing reality through the identification of 196 companies opened by these
      professionals. Afterwards, it was analyzed their time of functioning, the main
      economic activity of the company, capital value, percentage of nurse partners and
      the distribution of companies by region of Sao Paulo State.

PMID- 25946494
TI  - Predictive value of the Manchester Triage System: evaluation of patients'
      clinical outcomes.
AB  - OBJECTIVE: To analyze the predictive value of the Manchester Triage System in
      relation to clinical outcome of patients. METHODS: Prospective observational
      study of 577 patients admitted to the ER and subjected to risk classification.
      The Therapeutic Intervention Scoring System-28 (TISS-28) was used to measure the
      severity of patients (primary outcome) and secondary outcomes: high / transfer,
      death, and length of hospital stay. Descriptive and univariate analyzes were
      conducted. RESULTS: Patients classified as red are 10.7 times more likely to have
      scores above 14 in TISS-28 in relation to others. Patients classified as red have
      5.9 times more chance of progression to death compared to others. Patients of
      high priority service are 1.5 times more likely to be hospitalized over five days
      than low priority. CONCLUSIONS: STM proved a good predictor of clinical outcomes.

PMID- 25946495
TI  - Adherence and knowledge about the use of personal protective equipment among
      manicurists.
AB  - OBJECTIVE: This study aimed to assess adherence and knowledge of
      manicures/pedicures on the use of Personal Protective Equipment (PPE). METHODS:
      It was a survey with 235 manicures/pedicures in salons, Belo Horizonte/Brazil.
      Data were analyzed with the software Statistical package for the social sciences
      (17.0), using descriptive statistics, chi-square and logistic regression.
      RESULTS: The adherence and the knowledge of the professional were evaluated using
      the median of the results, obtaining 52% and 63% respectively. The professionals
      younger than 31 were more likely (2.54 times) to adhere to PPE and those who
      claimed to have done biosafety course and to use uniform during work, had better
      chance of understanding (2.86 and 3.12 times, respectively). The majority (83.4
      %) stated that the use of PPE should occur for all procedures, meanwhile 71.5 %
      cited not use them. CONCLUSIONS: The results indicate the poor adherence to PPE,
      strengthen occupational biological risk and need for training of these
      professionals.

PMID- 25946496
TI  - Prevalence of non-adherence to antihypertensive pharmacotherapy and associated
      factors.
AB  - OBJECTIVE: The aim of the study was to determine the prevalence of non-adherence
      to antihypertensive drug treatment and its association with factors bio-socio
      economic and welfare. METHOD: It was a descriptive, cross-sectional study,
      performed with 422 hypertensive individuals. Data were collected through home
      interviews, conducted between December 2011 and March 2012. RESULTS: The results
      showed that the respondents were mostly female, married, elderly, low income and
      little time of diagnosis. Were considered non adherent to medication 42.65% of
      participants. Non-Caucasian hypertensive patients, with fewer than eight years of
      schooling, who did not regularly attend doctor's appointments, took more than two
      anti-hypertensive medications and did not have private health insurance, showed
      higher likelihood of not complying with the drug treatment. CONCLUSION: These
      findings suggest that hypertensive patients with unfavorable socioeconomic
      characteristics and difficulty of access to the service require different
      interventions in order to encourage them to adhere to medication treatment.

PMID- 25946497
TI  - Family functionality in oldest old household residents.
AB  - OBJECTIVE: The aim of this study was to identify factors associated with family
      functionality of non-institutionalized long-lived subjects, who were residents in
      Goiania (GO), Brazil. METHOD: This was a population-based epidemiological study
      with cross-sectional outline. Evaluation scales of the functional and cognitive
      capacities were used. Family dynamics was measured using the Adaptation,
      Partnership, Growth, Affection, and Resolve (APGAR) instrument by making home
      interviews with 131 long-lived individuals. RESULTS: There was prevalence of the
      female gender, average of age of 83.87 years old, widowhood condition, and
      residence in a big family, primary schooling, and self-perception of regular
      health. A great amount showed independence for self-care and partial dependence
      for daily life instrumental activities. Family functionality prevailed with score
      average of 9.06 points. CONCLUSION: In conclusion, family functionality in long
      lived subjects is associated with self-perception of poor/bad health,
      osteoporosis, and fall. Results allowed characterizing long-lived subjects'
      family functionality with the aim of valuing and prioritizing family as a
      caregiver.

PMID- 25946498
TI  - The decreasing number of cigarettes during psychiatric hospitalization:
      intervention or punishment?
AB  - The smoking ban during psychiatric hospitalization provokes personal and
      institutional changes. OBJECTIVE: To identify the mental disorders carriers'
      perception, the smokers ones, about the decreasing number of cigarettes during
      psychiatric hospitalization. METHOD: Exploratory study with 96 hospitalized
      carriers of mental disorders who are smokers: G1 (34 subjects hospitalized when
      was allowed one cigarette by hour) and G2 (62 subjects hospitalized when it was
      reduced to eight cigarette by day). Semi-structured questionnaire. Thematic
      content analysis. RESULTS: The G1 admitted satisfaction with the restriction-
      smoking during hospitalization as entitlement. The G2 resists the restriction
      change occurred without dialogue or support. In spite of the difficulties, some
      attitude changes about the cigarette were noticed such as increase of the
      responsibility, discovery of the ability to reduce smoking and the meaning of its
      role. CONCLUSION: Some subjects understand the smoking health policy change as
      punishment, while others as opportunity to think about the role of cigarette in
      their life.

PMID- 25946499
TI  - Factors associated with immunization against Hepatitis B among workers of the
      Family Health Strategy Program.
AB  - Cross-sectional study conducted among workers of the Family Health Strategy
      Montes Claros. OBJECTIVE: To investigate the report of vaccination against
      Hepatitis B, verification of immunization and the factors associated with dosages
      of anti-HBs. METHOD: We collected blood samples from those reported that they had
      one or more doses of the vaccine. We evaluated the association of the dosage of
      anti- HBs with sociodemographic conditions, occupational and behavioral. The
      associations were verified by Mann Whitney and Kruskal Wallis and correlation
      Spermann by linear regression using SPSS(r) 17.0. RESULTS: Among the 761
      respondents, 504 (66.1%) were vaccinated, 52.5 % received three doses, 30.4 %
      verified immunization. Of the 397 evaluated for the determination of anti-Hbs,
      16.4% were immune. CONCLUSION: It was found that longer duration of work was
      associated with higher levels of anti-HBs, while levels of smoking were inversely
      associated with anti-HBs. These workers need for vaccination campaigns.

PMID- 25946500
TI  - Prevalence of minor psychiatric disorders in socio-educational agents in the
      state of Rio Grande do Sul.
AB  - OBJECTIVE: To determine the prevalence and factors associated with minor
      psychiatric disorders (MPD) in socio-educational agents. METHOD: It is a cross
      sectional study with 381 socio-educational agents the Centers for Socio
      Educational Services in the State of Rio Grande do Sul, Brazil. The Brazilian
      versions of the Scale of Demand-control-social support at work and the Self
      Reporting Questionnaire-20 have been applied. RESULTS: The results showed a
      prevalence of suspicion MPD of 50.1%. They showed to be related to suspicion of
      MPD : being female (55.7%), having age up to 44 years old (58.5%), no physical
      activity (57.4%), do not have time for leisure (75%), make use of medication
      (61.4%), require medical attention (56.9%) and psychological counseling (72.7%),
      not being satisfied with the workplace (61.7%) and need for time off from work
      (65.6%). CONCLUSION: The study provides important data about the mental health of
      agents, showing the need for the involvement of managers and of the health
      service of worker's health in planning actions to promote health of these
      workers.

PMID- 25946501
TI  - Patients with disorders of consciousness: vital, facial and muscular responses to
      music or messages.
AB  - PURPOSES: To compare vital signs, facial expression and basal electroneurographic
      signs with measures during stimuli music, message or "silence" in coma patients,
      vegetative status or sedated; and relating the score of Glasgow Results Scale
      with the intervention realized. METHOD: A Monoblind Transversal Controlled
      Clinical Trial to researcher. The distribution, among the three groups, was
      randomized (experiment with music, experiment with message or control). Two
      assessments (sessions) were performed with interval of 40 minutes on the same
      day. RESULTS: Most of the 76 patients were male, between 18 to 36 years old and
      hospitalized due to trauma. Statistically significant changes were found in the
      variables referred to temperature, facial expression, electroneurography and
      Glasgow Results Scale; more frequent alterations in second session, in coma and
      vegetative patients, in frontal muscles and in experiment group. CONCLUSIONS: The
      facial expression and the electroneurography seem to be more trustworthy
      variables than vital signs to evaluate consciousness.

PMID- 25946502
TI  - Adherence to foot self-care in diabetes mellitus patients.
AB  - OBJECTIVE: To analyze the self-care of patients with type 2 diabetes mellitus in
      the Family Health Strategy in Teresina-PI. METHOD: Search cross selected by
      simple random sampling, 331 people with diabetes mellitus. Data collection took
      place from August to December 2012 with the use of Self-Care Activities
      Questionnaire with Diabetes and structured instrument for recording information
      socioeconomic and guidance received by the professional nurse. RESULTS: The data
      revealed that patients have poor adherence to blood glucose monitoring, the
      physical exercise and foot care, but with good adherence to the medication. Only
      38.7% of the sample examined the feet of fi ve to seven days a week.
      Statistically significant association between self-care activities with their
      feet and orientations of nurses (p < 0,05). CONCLUSION: That there is need to
      raise awareness with regard to the development of skills for self-care.

PMID- 25946503
TI  - Chinese auriculotherapy to improve quality of life of nursing team.
AB  - OBJECTIVE: To evaluated the efficacy of auriculotherapy for improving quality of
      life and reducing stress in nursing staff. METHOD: Single-blind radomizad
      clinical trail envolving 175 subjects randomized in: Control (G1), Protocol Group
      (G2) and without Protocol Group (G3). They were evaluated by the Stress Symptoms
      List and SF36v2 at baseline, after 12 sessions and follow up (30 days), between
      January and July 2012. RESULTS: Both intervention groups reduced stress (p <0.05)
      with greater effect for G3 (d = 1.15). G3 was also higher for improving life
      quality especially the physical domain (p = 0.05). CONCLUSION: Individualized
      auriculotherapy (G3) had greater effect compared to the protocol auriculotherapy
      (G2) for reducing stress and improving life quality.

PMID- 25946504
TI  - BANFISA and (IN) DICA-SUS in health undergraduate education: playing and learning
      construction.
AB  - OBJECTIVES: To analyze the learning built during the matches of the games by
      students of the subject Gestao de Politicas Publicas em Saude at the Universidade
      de Brasilia. METHOD: Exploratory, descriptive research, in a qualitative
      approach, with 26 students from various graduation courses in health, using a
      questionnaire and participant observation. RESULTS: Participants reinvented
      rules, related issues addressed in the games to the reality, interacted with
      colleagues and had fun throughout the match. Comparing the games in relation to
      ludicity, the BANFISA was more attractive than the (IN) DICA-SUS, although they
      are complementary. CONCLUSIONS: Learning constructed by the students goes beyond
      the content of the subject; involve the active participation in group and
      creativity.

PMID- 25946505
TI  - Prevention and non-pharmacological management of pain in newborns.
AB  - OBJECTIVE: To describe the main non-pharmacological interventions for pain relief
      in newborns available in Neonatal Intensive Care Unit. METHOD: An exploratory
      search of the MedLine, Lilacs and Scielo online databases was conducted to
      retrieve references of studies published from 2004 to 2013. RESULTS: Several non
      pharmacological interventions were shown to be effective, to represent low risk
      for neonates and to have a low operational cost. The ones most often discussed in
      the literature were: oral administration of glucose/sucrose, non-nutritive
      sucking, breastfeeding, skin-to-skin contact, facilitated tucking and swaddling.
      CONCLUSION: Healthcare teams should be familiar with these methods and use them
      more effectively in Neonatal Intensive Care Unit daily routines, so as to ensure
      that newborns receive qualified and more human care.

PMID- 25946506
TI  - Community-acquired methicillin-resistant Staphylococcus aureus: a global problem.
AB  - OBJECTIVE: To describe the epidemiology of CA-MRSA cases in Brazil order to
      understand its occurrence, risk factors and forms of management in the country
      compared with the worldwide situation. METHOD: Literature review and for articles
      selection considering the databases: Scopus, Science Direct, Isi Web of
      Knowledge, PubMed and BVS. RESULTS: Ten national articles describing 21 cases of
      CA-MRSA were identified, mostly in children, adolescents and adults with skin and
      soft tissue infection progressing to severe infections related to Oceania
      Southwest Pacific Clone (OSPC) leading to hospitalization. Conclusion: Although
      CA-MRSA is considered a global important microorganism we found a lack of
      published data about its epidemiology in Brazil, which hinder the design of the
      reality of the country against CA-MRSA.

PMID- 25946507
TI  - Adverse events and safety in nursing care.
AB  - OBJECTIVE: To identify the scientific publications about adverse events in
      nursing care in adult hospitalized patients and discuss the main adverse events
      in nursing care. METHOD: Integrative revision with a qualitative approach. The
      data were collected at LILACS, MEDLINE, BDENF and the library SCIELO and were
      submitted to thematic analysis. RESULTS: Three categories were developed: Adverse
      events in nursing care; The main causes of the adverse events in nursing care;
      Attitude of nursing professionals in face of errors. The main events were
      identified in nursing care with emphasis on the medication error, the failure to
      perform dressings and falls of patients. The importance of instruments was
      emphasized for notification of adverse events in the institutions. However the
      fear of punishment on professionals stimulates the underreporting of events.
      CONCLUSION: It is important to discuss effective prevention strategies that
      ensure patient safety in healthcare institutions.

PMID- 25946508
TI  - Nursing diagnoses and interventions for a child after cardiac surgery in an
      intensive care unit.
AB  - OBJECTIVE: To describe the nursing clinical judgment as a basis for ND
      identification and development of a NIC treatment plan for a child after cardiac
      surgery under intensive care. METHOD: A case study with data retrospectively
      collected from charts. RESULTS: Three nurses identified NANDA-I diagnoses and NIC
      interventions. A 6-month-old child submitted to cardiac surgery, requiring
      extracorporeal membrane oxygenation in the postoperative period. Four main
      nursing diagnoses were identified, towards which ten interventions were directed.
      The proposal of interventions to respond to the priority human responses of the
      child was optimized by the use of standard terminologies. Every nursing diagnosis
      was supported by diagnostic indicators; every intervention was scientifically
      supported. CONCLUSION: There must be an expectation that nurses address not only
      physiological responses, but also those within psychosocial domains.

PMID- 25946509
TI  - Multifunctional self-assembled composite colloids and their application to SERS
      detection.
AB  - We present a simple method for the co-encapsulation of gold nanostars and iron
      oxide nanoparticles into hybrid colloidal composites that are highly responsive
      to both light and external magnetic fields. Self-assembly was driven by
      hydrophobic interactions between polystyrene capped gold nanostars and iron oxide
      nanocrystals stabilized with oleic acid, upon addition of water. A block
      copolymer was then used to encapsulate the resulting spherical colloidal particle
      clusters, which thereby became hydrophilic. Electron microscopy analysis
      unequivocally shows that each composite particle comprises a single Au nanostar
      surrounded by a few hundreds of iron oxide nanocrystals. We demonstrate that this
      hybrid colloidal system can be used as an efficient substrate for surface
      enhanced Raman scattering, using common dyes as model molecular probes. The co
      encapsulation of iron oxide nanoparticles renders the system magnetically
      responsive, so that application of an external magnetic field leads to particle
      accumulation and limits of detection are in the nM range. 

PMID- 25946511
TI  - Arrays of Molecular Rotors with Triptycene Stoppers: Surface Inclusion in
      Hexagonal Tris(o-phenylenedioxy)cyclotriphosphazene.
AB  - A new generation of rod-shaped dipolar molecular rotors designed for controlled
      insertion into channel arrays in the surface of hexagonal tris(o
      phenylenedioxy)cyclotriphosphazene (TPP) has been designed and synthesized.
      Triptycene is used as a stopper intended to prevent complete insertion, forcing
      the formation of a surface inclusion. Two widely separated (13)C NMR markers are
      present in the shaft for monitoring the degree of insertion. The structure of the
      two-dimensional rotor arrays contained in these surface inclusions was examined
      by solid-state NMR and X-ray powder diffraction. The NMR markers and the
      triptycene stopper functioned as designed, but half of the guest molecules were
      not inserted as deeply into the TPP channels as the other half. As a result, the
      dipolar rotators were distributed equally in two planes parallel to the crystal
      surface instead of being located in a single plane as would be required for
      ferroelectricity. Dielectric spectroscopy revealed rotational barriers of ~4
      kcal/mol but no ferroelectric behavior. 

PMID- 25946510
TI  - The predictive power of family history measures of alcohol and drug problems and
      internalizing disorders in a college population.
AB  - A family history (FH) of psychiatric and substance use problems is a potent risk
      factor for common internalizing and externalizing disorders. In a large web-based
      assessment of mental health in college students, we developed a brief set of
      screening questions for a FH of alcohol problems (AP), drug problems (DP) and
      depression-anxiety in four classes of relatives (father, mother,
      aunts/uncles/grandparents, and siblings) as reported by the student. Positive
      reports of a history of AP, DP, and depression-anxiety were substantially
      correlated within relatives. These FH measures predicted in the student, in an
      expected pattern, dimensions of personality and impulsivity, alcohol consumption
      and problems, smoking and nicotine dependence, use of illicit drugs, and symptoms
      of depression and anxiety. Using the mean score from the four classes of
      relatives was more predictive than using a familial/sporadic dichotomy.
      Interactions were seen between the FH of AP, DP, and depression-anxiety and peer
      deviance in predicting symptoms of alcohol and tobacco dependence. As the
      students aged, the FH of AP became a stronger predictor of alcohol problems.
      While we cannot directly assess the validity of these FH reports, the pattern of
      findings suggest that our brief screening items were able to assess, with some
      accuracy, the FH of substance misuse and internalizing psychiatric disorders in
      relatives. If correct, these measures can play an important role in the creation
      of developmental etiologic models for substance and internalizing psychiatric
      disorders which constitute one of the central goals of the overall project.

PMID- 25946512
TI  - The Effect of Kinesio Taping on Anterior Knee Pain Consistent With Patellofemoral
      Pain Syndrome: A Critically Appraised Topic.
AB  - CLINICAL SCENARIO: Patellofemoral pain syndrome (PFPS) occurs in 25% of
      adolescents and adults and is the leading cause of knee pain in runners. Pain is
      commonly felt when ascending or descending stairs, deep squatting, kneeling, or
      running. There is no consensus on the etiology of this condition, but
      insufficient hip strength, malalignment of the lower extremity, hyperpronation of
      the foot, and patellar incongruence have been suggested. Common treatments of
      PFPS include strengthening of quadriceps and hip muscles, McConnell taping,
      electrical stimulation, and foot orthotics, but effectiveness of these treatments
      is inconclusive. Kinesio Taping is an alternative taping technique for
      musculoskeletal injuries including PFPS. Although research suggests that Kinesio
      Taping decreases pain and improves range of motion for some musculoskeletal
      injuries, its effectiveness in decreasing pain in patients with PFPS in unknown.
      Furthermore, Kinesio Taping has not been compared with other taping techniques
      including McConnell taping. Focused Clinical Question: For patients with anterior
      knee pain consistent with PFPS, does treatment with Kinesio Taping decrease pain
      more than McConnell taping or no tape at all?

PMID- 25946513
TI  - Effects of lisdexamfetamine alone and in combination with s-citalopram on
      acetylcholine and histamine efflux in the rat pre-frontal cortex and ventral
      hippocampus.
AB  - Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder
      characterized by poor attention, impulse control and hyperactivity. A significant
      proportion of ADHD patients are also co-morbid for other psychiatric problems
      including mood disorders and these patients may be managed with a combination of
      psychostimulants and anti-depressants. While it is generally accepted that
      enhanced catecholamine signalling via the action of psychostimulants is likely
      responsible for the cognitive improvement in ADHD, other neurotransmitters
      including acetylcholine and histamine may be involved. In the present study, we
      have examined the effect of lisdexamfetamine dimesylate (LDX), an amphetamine pro
      drug that is approved for the treatment of ADHD on acetylcholine and histamine
      efflux in pre-frontal cortex and hippocampus alone and in combination with the
      anti-depressant s-citalopram. LDX increased cortical acetylcholine efflux, an
      effect that was not significantly altered by co-administration of s-citalopram.
      Cortical and hippocampal histamine were markedly increased by LDX, an effect that
      was attenuated in the hippocampus but not in pre-frontal cortex when co
      administered with s-citalopram. Taken together, these results suggest that efflux
      of acetylcholine and histamine may be involved in the therapeutic effects of LDX
      and are differentially influenced by the co-administration of s-citalopram.
      Attention deficit hyperactivity disorder (ADHD) is characterized by poor
      attention, impulse control and hyperactivity. Some ADHD patients are also co
      morbid for mood disorders and may be managed with psychostimulants (e.g.
      lisdexamfetamine, LDX) and anti-depressants (e.g. s-citalopram). LDX increased
      the efflux of acetylcholine and histamine, neurotransmitters involved in
      cognitive function, which were differentially influenced when co-administered
      with s-citalopram. Acetylcholine and histamine may be involved in the therapeutic
      effects of LDX and are differentially affected by the co-administration of s
      citalopram. 

PMID- 25946514
TI  - When are antifreeze proteins in solution essential for ice growth inhibition?
AB  - Antifreeze proteins (AFPs) are a widespread class of proteins that bind to ice
      and facilitate the survival of organisms under freezing conditions. AFPs have
      enormous potential in applications that require control over ice growth. However,
      the nature of the binding interaction between AFPs and ice remains the subject of
      debate. Using a microfluidics system developed in-house we previously showed that
      hyperactive AFP from the Tenebrio molitor beetle, TmAFP, remains bound to an ice
      crystal surface after exchanging the solution surrounding the ice crystal to an
      AFP-free solution. Furthermore, these surface-adsorbed TmAFP molecules sufficed
      to prevent ice growth. These experiments provided compelling evidence for the
      irreversible binding of hyperactive AFPs to ice. Here, we tested a moderately
      active type III AFP (AFPIII) from a fish in a similar microfluidics system. We
      found, in solution exchange experiments that the AFPIIIs were also irreversibly
      bound to the ice crystals. However, some crystals displayed "burst" growth during
      the solution exchange. AFPIII, like other moderately active fish AFPs, is unable
      to bind to the basal plane of an ice crystal. We showed that although moderate
      AFPs bound to ice irreversibly, moderate AFPs in solution were needed to inhibit
      ice growth from the bipyramidal crystal tips. Instead of binding to the basal
      plane, these AFPs minimized the basal face size by stabilizing other crystal
      planes that converge to form the crystal tips. Furthermore, when access of
      solution to the basal plane was physically blocked by the microfluidics device
      walls, we observed enhancement of the antifreeze activity. These findings provide
      direct evidence that the weak point of ice growth inhibition by fish AFPs is the
      basal plane, whereas insect AFPs, which can bind to the basal plane, are able to
      inhibit its growth and thereby increase antifreeze activity. 

PMID- 25946516
TI  - Comparison of diagnoses of amyotrophic lateral sclerosis by use of death
      certificates and hospital discharge data in the Danish population.
AB  - Because ALS is rare, large-scale studies are difficult. Hospital and death
      certificate data are valuable tools, but understanding of how well they capture
      cases is needed. We identified 3650 incident cases in the Danish National Patient
      Register (NPR) between 1982 and 2009, using ICD-8 (before 1994) or ICD-10 codes.
      Death certificates were obtained from the Danish Register of Causes of Death. We
      obtained medical records for 173 of the cases identified in the NPR and
      classified these according to the El Escorial criteria. We compared ALS
      identification from death certificates to hospital discharges, and both to
      medical records. Results showed that the sensitivity for use of death
      certificates was 84.2% (95% CI 82.9-85.5%) and was significantly higher for
      females, subjects younger than 77 years, and when coded with ICD-8. Using only
      the underlying cause of death resulted in significantly lower sensitivity. The
      estimated overall positive predictive value (PPV) was 82.0% (95% CI 80.0-83.8%).
      Sensitivity and PPV were similar compared with medical records. In conclusion, we
      found that use of hospital discharges and death certificates is highly reliable
      and, therefore, a valuable tool for ALS epidemiologic studies. The possible
      effects on findings of slight differences by age, gender, and ICD coding should
      be considered. 

PMID- 25946518
TI  - Origin of fast catalysis in allylic amination reactions catalyzed by Pd-Ti
      heterobimetallic complexes.
AB  - Experiments and density functional calculations were used to quantify the impact
      of the Pd-Ti interaction in the cationic heterobimetallic
      Cl2Ti(N(t)BuPPh2)2Pd(eta(3)-methallyl) catalyst 1 used for allylic aminations.
      The catalytic significance of the Pd-Ti interaction was evaluated computationally
      by examining the catalytic cycle for catalyst 1 with a conformation where the Pd
      Ti interaction is intact versus one where the Pd-Ti interaction is severed.
      Studies were also performed on the relative reactivity of the cationic
      monometallic (CH2)2(N(t)BuPPh2)2Pd(eta(3)-methallyl) catalyst 2 where the Ti from
      catalyst 1 was replaced by an ethylene group. These computational and
      experimental studies revealed that the Pd-Ti interaction lowers the activation
      barrier for turnover-limiting amine reductive addition and accelerates catalysis
      up to 10(5). The Pd-Ti distance in 1 is the result of the N(t)Bu groups enforcing
      a boat conformation that brings the two metals into close proximity, especially
      in the transition state. The turnover frequency of classic Pd pi allyl complexes
      was compared to that of 1 to determine the impact of P-Pd-P coordination angle
      and ligand electronic properties on catalysis. These experiments identified that
      cationic (PPh3)2Pd(eta(3)-CH2C(CH3)CH2) catalyst 3 performs similarly to 1 for
      allylic aminations with diethylamine. However, computations and experiment reveal
      that the apparent similarity in reactivity is due to very fast reaction kinetics.
      The higher reactivity of 1 versus 3 was confirmed in the reaction of methallyl
      chloride and 2,2,6,6-tetramethylpiperidine (TMP). Overall, experiments and
      calculations demonstrate that the Pd-Ti interaction induces and is responsible
      for significantly lower barriers and faster catalysis for allylic aminations. 

PMID- 25946517
TI  - Maternal iron status in early pregnancy and birth outcomes: insights from the
      Baby's Vascular health and Iron in Pregnancy study.
AB  - Fe deficiency anaemia during early pregnancy has been linked with low birth
      weight and preterm birth. However, this evidence comes mostly from studies
      measuring Hb levels rather than specific measures of Fe deficiency. The present
      study aimed to examine the association between maternal Fe status during the
      first trimester of pregnancy, as assessed by serum ferritin, transferrin receptor
      and their ratio, with size at birth and preterm birth. In the Baby VIP (Baby's
      Vascular health and Iron in Pregnancy) study, we recruited 362 infants and their
      mothers after delivery in Leeds, UK. Biomarkers were measured in maternal serum
      samples previously obtained in the first trimester of pregnancy. The cohort
      included sixty-four (18 %) small for gestational age (SGA) babies. Thirty-three
      babies were born preterm (9 %; between 34 and 37 weeks). First trimester maternal
      Fe depletion was associated with a higher risk of SGA (adjusted OR 2.2, 95 % CI
      1.1, 4.1). This relationship was attenuated when including early pregnancy Hb in
      the model, suggesting it as a mediator (adjusted OR 1.6, 95 % CI 0.8, 3.2). For
      every 10 g/l increase in maternal Hb level in the first half of pregnancy the
      risk of SGA was reduced by 30 % (adjusted 95 % CI 0, 40 %); levels below 110 g/l
      were associated with a 3-fold increase in the risk of SGA (95 % CI 1.0, 9.0).
      There was no evidence of association between maternal Fe depletion and preterm
      birth (adjusted OR 1.5, 95 % 0.6, 3.8). The present study shows that depleted Fe
      stores in early pregnancy are associated with higher risk of SGA. 

PMID- 25946519
TI  - Academic Global Surgery: A Moral Imperative.

PMID- 25946520
TI  - Creation of reduced graphene oxide based field effect transistors and their
      utilization in the detection and discrimination of nucleoside triphosphates.
AB  - Two low-cost, micropatterned, solution-gated field effect transistors (modified
      FET and unmodified FET) based on reduced graphene oxide (RGO) were developed and
      used for detection and discrimination of nucleoside triphosphates (NTPs). The
      modified FET was realized by simple deposition of a positively charged bis
      pyrenyl derivative, py-diIM-py, onto the conducting RGO strips of the unmodified
      FET. The electrical properties and sensing behaviors of the as-prepared devices
      were studied comprehensively. Electrical transfer property tests revealed that
      both of the two FETs exhibit V-shaped ambipolar field effect behavior from p-type
      region to n-type region. Sensing performance studies demonstrated that
      modification of the native FET with py-diIM-py improves its sensing ability to
      NTPs-GTP and ATP in particular. The detection limit of GTP and ATP was as low as
      400 nM, which is the lowest value for graphene-based electronic sensors reported
      so far. Furthermore, based on the cross-reactive responses of the two devices to
      NTPs, NTPs can be conveniently distinguished via combining use of the two
      devices. The enhancement of the modifier (py-diIM-py) to the sensing performance
      of the FET is tentatively attributed to its possible mediation role in sticking
      onto RGO strips and accumulating analytes by electrostatic association with the
      relevant species. Because they are sensitive and fast in response, simple and low
      cost in preparation, and possibly useful in sensor-array fabrication, the
      developed sensors show great potential in real-life application. 

PMID- 25946521
TI  - Light Weight and Flexible High-Performance Diagnostic Platform.
AB  - A flexible diagnostic platform is realized and its performance is demonstrated
      for early detection of avian influenza virus (AIV) subtype H1N1 DNA sequences.
      The key component of the platform is high-performance biosensors based on high
      output currents and low power dissipation Si nanowire field effect transistors
      (SiNW-FETs) fabricated on flexible 100 MUm thick polyimide foils. The devices on
      a polymeric support are about ten times lighter compared to their rigid
      counterparts on Si wafers and can be prepared on large areas. While the latter
      potentially allows reducing the fabrication costs per device, the former makes
      them cost efficient for high-volume delivery to medical institutions in, e.g.,
      developing countries. The flexible devices withstand bending down to a 7.5 mm
      radius and do not degrade in performance even after 1000 consecutive bending
      cycles. In addition to these remarkable mechanical properties, on the analytic
      side, the diagnostic platform allows fast detection of specific DNA sequences of
      AIV subtype H1N1 with a limit of detection of 40 * 10(-12) m within 30 min
      suggesting its suitability for early stage disease diagnosis. 

PMID- 25946523
TI  - [On disease association].

PMID- 25946522
TI  - Laser-induced acoustic desorption of natural and functionalized biochromophores.
AB  - Laser-induced acoustic desorption (LIAD) has recently been established as a tool
      for analytical chemistry. It is capable of launching intact, neutral, or low
      charged molecules into a high vacuum environment. This makes it ideally suited to
      mass spectrometry. LIAD can be used with fragile biomolecules and very massive
      compounds alike. Here, we apply LIAD time-of-flight mass spectrometry (TOF-MS) to
      the natural biochromophores chlorophyll, hemin, bilirubin, and biliverdin and to
      high mass fluoroalkyl-functionalized porphyrins. We characterize the variation in
      the molecular fragmentation patterns as a function of the desorption and the VUV
      postionization laser intensity. We find that LIAD can produce molecular beams an
      order of magnitude slower than matrix-assisted laser desorption (MALD), although
      this depends on the substrate material. Using titanium foils we observe a most
      probable velocity of 20 m/s for functionalized molecules with a mass m = 10,000
      Da.

PMID- 25946524
TI  - [Analysis of clinical-biological features of adult acute lymphoblastic leukemia].
AB  - INTRODUCCTION: Acute lymphoblastic leukemia (ALL) is a clonal disease
      characterized by a proliferation of immature cells. In immunophenotypic,
      cytogenetic and molecular studies, it is a heterogeneous disease with diverse
      manifestations and prognoses. The treatment is complex and is associated with
      complications during its course. PATIENTS AND METHODS: A prospective study of
      cohort of patients with ALL. Subjects were recruited consecutively from April
      2010 to November 2012 in the Specialties Hospital, /MSS. RESULTS: We included 29
      patients with ALL; of 16 females (55%) and 13 males (45%), 18 (64%) were treated
      with modified BFM, seven (25%) HiperCVAD, and three (11 %) others. In all, 70%
      achieved complete remission, and 8.5% partial responses. Induction mortality in
      five patients (17%). Consolidation mortality in three (13%). Relapse 33%, with a
      mean of eight months (5- 16 months), overall survival five months. At 26 months
      of follow-up, 13 patients (45%) maintained RC. Disease-free survival of 10 months
      and overall survival of 12 months was observed. CONCLUSION: The majority of
      patients, regardless of risk, reach complete remission. We found that the
      clinical and biological characteristics showed no significant differences related
      to the outcome. lmmunochemotherapy treatment may improve response.

PMID- 25946525
TI  - [Pulmonary complications in pediatric patients with primary immunodeficiency].
AB  - INTRODUCTION: Primary immunodeficiencies comprise diseases that impair the immune
      system. Clinical manifestations are characterized by recurrent respiratory
      infections, which may be complicated by bronchiectasis, peribronchial thickening,
      abscesses, bullae, and pulmonary fibrosis. The aim of this study was to determine
      pulmonary complications in pediatric primary immunodeficiency by type. RESULTS.
      We included 65 patients, 28 patients with humoral immunodeficiency, four with
      cellular immunodeficiency, 13 with well-defined syndromes, and 20 with phagocytic
      defects. Patients with cellular immunodeficiency with symptoms began at an early
      age, and were diagnosed before one year of age (p = 0.01 ). Patients with humoral
      immunodeficiency had more frequent and early respiratory symptoms (p = 0.01 ).
      The most common respiratory diseases were acute suppurative otitis media, with
      sinusitis and pneumonia more common in humoral immunodeficiencies and phagocytic
      defects. The most common pulmonary complications were bronchiectasis and
      pulmonary fibrosis interstitial damage, with no statistical difference between
      primary immunodeficiency type. Pulmonary function tests showed greater impairment
      in patients with phagocyte defects, but no statistical difference (p = 0.28). The
      presence of pulmonary complications showed no difference when compared by type of
      immunodeficiency, agammaglobulinemia only (p = 0.02). CONCLUSIONS: Cell
      immunodeficiencies are diagnosed as early as the onset of symptoms before the
      patient is one year old. Humoral immunodeficiencies present maximum upper and
      lower respiratory infections and increased risk of pulmonary complications,
      especially agammaglobulinemia.

PMID- 25946526
TI  - [Zoledronic acid (zoledronate) in children with osteogenesis imperfecta].
AB  - INTRODUCTION: Zoledronic acid or zo/edronate is a potent bisphosphonate that
      recently has been used in children with osteoporosis and osteogenesis imperfecta
      (01), so it could be an option in the treatment of children with this terrible
      disease that virtually condemns them to a life of pain and prostration. The aim
      of this study was to evaluate the clinical and biochemical conditions of
      pediatric patients with 01 before and after treatment with zo /edronate. RESULTS:
      We included 14 patients, median age six years (6 months to 14 years), eight (57.1
      %) males and six (42 .9%) females, weight 19 kg (5.8-45 kg). According to the
      type of 01, six (42.9%) were type I, six (42.9%) type Ill, and two (14.2%) type
      IV The functional score (Bleck) previous to treatment was 4 (1-9) and 6 (2-9)
      after treatment (p = 0.001). Pain intensity prior to zo/edronate was 2 (1-9) and
      0 (0-2) after (p = 0.008). Previous fractures five (1-15) and post-treatment one
      (0-2) (p = 0.001 ). There were no significant differences in calcium, phosphorus,
      alkaline phosphatase, and parathyroid hormone. CONCLUSIONS: Zoledronic acid
      decreases the number of bone fractures and pain in children with osteogenesis
      imperfect and improves functional status. The most common side effects were fever
      and bone pain within five days after the infusion,which disappear paracetamol. No
      adverse long-term effects such as hypocalcemia or hypoparathyroidism were
      reported.

PMID- 25946528
TI  - [Clinical Characteristics of antineutrophil cytoplasmic antibody-associated
      vasculitis in a respiratory diseases referral center in Mexico (1982-2010)].
AB  - INTRODUCTION: Respiratory manifestations in antineutrophil cytoplasmic antibody
      associated vasculitis (AASV) are common, though their suspicion is lower than
      expected in respiratory devoted centers, with few descriptions coming from them.
      OBJECTIVE: To describe the clinical, paraclinical and radiological
      manifestations, plus the prognosis of AASV patients seen in a respiratory
      referral center in Mexico City. MATERIAL AND METHODS: Retrospective review of
      patients with final diagnosis of AASV, based on the American College of
      Rheumatology criteria and the 1994 Chapel Hill Consensus Conference Nomenclature,
      from 1982 to 2010. RESULTS: The characteristics of 74 granulomatosis with
      polyangiitis, 10 microscopic polyangiitis, and six eosinophilic granulomatosis
      with polyangiitis cases are described. Mean time elapsed from initial suspicion
      to definitive diagnosis was 30 months. As expected, respiratory findings
      dominated this cohort, but no significant differences were observed when compared
      to other series with AAS?1, except for a higher frequency of subglottic stenosis.
      After a mean follow-up of 22 months, 83% of patients were alive, with remission
      being achieved in 87% and response in 9%. Seven patients died, mostly from
      infectious complications. CONCLUSION: This study documents that airway
      manifestations in Mexican patients with AASV are similar to what has been
      previously described. However, time to diagnosis is long. Respiratory specialists
      should be more aware of the modes of presentation in AASV patients in order to
      facilitate their recognition.

PMID- 25946527
TI  - [Prevalence, associated factors and phenomenology of psychosis in patients with
      Parkinson's disease].
AB  - INTRODUCTION: Psychosis associated with Parkinson's disease is a major
      neuropsychiatric complication; it has been reported that 60% of patients will
      develop psychosis during the disease evolution. Its pathophysiology is
      multifactorial and clinically psychotic phenomena include minor hallucinations
      and confusional states. MATERIAL AND METHODS: We performed a cross-sectional
      study in patients with Parkinson's disease from a tertiary hospital using a
      thoughtful neurological and neuropsychiatric evaluation along with specific
      scales for non-motor symptoms, depression, cognition, and presence and severity
      of psychotic symptoms and hallucinations. RESULTS: We included a total of 236
      patients with Parkinson's disease, of which 33 (13.9%) patients met the criteria
      for psychosis at the time of the evaluation. Visual hallucinations were the most
      common symptom. Age (p = 0.004), age at onset of the disease (p = 0.007) and its
      duration (p = 0.004), use of levodopa (p = 0.02), and use of amantadine (p =
      0.004) were the main factors associated with the presence of psychosis.
      CONCLUSION: Psychosis in Parkinson's disease is a relatively common manifestation
      and is mainly associated with clinical and demographic factors. Early recognition
      will optimize management and improve the quality of life of patients and their
      caregivers.

PMID- 25946529
TI  - [Depression in school children and adolescents carriers of acute leukemia during
      the treatment phase].
AB  - Objective: To describe depression levels in school aged children and adolescents
      with acute leukemia during the treatment. MATERIALS AND METHODS: This transversal
      descriptive study took place during January to September 2012 and included school
      aged children and adolescents, carriers of acute leukemia, in treatment at a high
      ranking specialty hospital. A modified Kovacs questionnaire (C O/) was applied.
      They were grouped according to presence or absence of depression. Inferential
      statistics with x2 and Statistical package SPSS 20.0 were used. RESULTS: Forty
      six patients were included in the study: with depression n = 43 (94%), without
      depression n=3 (6%), males n= 32 (70%) and females n=14 (30%), average age 8
      years old (7-15). Acute lymphoblast leukemia was the most frequent n=42 patients
      (91 %). Depression was found in 42 patients (91 "'o), with nine presenting a
      minor level (21 "'o), 11 a moderate level (26 "/o), and 23 a severe level (53
      "/o). Mostly during the consolidation phase, 30 patients (70"/o) patients with no
      relapses showed a higher incidence of depression, 23 (54 "/o) vs. with relapses
      20 (47"/o) (p = 0.870); the majority had no family history of depression 41 (95
      "/o) vs. 2 (5"/o) (p = 0.017). CONCLUSIONS: We found a high percentage of severe
      level depression, which affected mostly male patients, suffering a relapse during
      the consolidation treatment phase.

PMID- 25946530
TI  - [Clinical risk index for babies II (CRIB II) and weight to predict mortality in
      preterm infants less than 32 weeks treated with surfactant].
AB  - OBJECTIVE: To determine the usefulness of the Clinical Risk Index for Babies II
      (CRIB II) and weight to predict mortality in preterm infants < 32 weeks treated
      with exogenous surfactant. MATERIAL AND METHODS: Design: cohort for diagnostic
      test. Preterm babies < 32 weeks who received exogenous surfactant in a third
      level of care were included. The cutoff for CRIB II was evaluated and considered
      as score > 10 and weight < 750 grams; monitoring was performed until discharge or
      death. RESULTS: RNP data analyzed 105 babies; 55/105 (52%) were female, the mean
      value +/- 1.4 weight 2 grams and 29 + 2 weeks gestational age. Mortality was
      found in 16/105, of which 15/16 had a score > 10 on the CRIB II index. Survival
      was found in 89/105 and index > 10 points in 2/89. Based on these results we
      found: sensitivity 93%, specificity 98%, positive predictive value 88 "/o,
      negative predictive value 98"/o . With weight < 750 grams, mortality occurred in
      10/16 and survival in 17189; sensitivity 62 "/o, specificity 81 "/o, positive
      predictive value 37%, and negative predictive value 92%. CONCLUSIONS: The CRIB II
      index is more useful than weight for predicting mortality in preterm infants less
      than 32 weeks treated with surfactant.

PMID- 25946531
TI  - [Alcohol, and tobacco consumption and sports practice in Mexican and Spanish
      university students and the association between quality of life and health and
      sensation seeking].
AB  - OBJECTIVE: To analyze the alcohol, and tobacco consumption and sports practice
      for Mexican and Spanish and its relation to sensation seeking. Methods: 309
      university students participated, 154 Spanish and 155 Mexican. We used the
      Sensation Seeking Scale (SSS-V), the health survey Short-Form 36 (SF-36) and a
      lifestyle questionnaire conducted ad hoc. RESULTS: Mexican Students often have
      lower consumption of tobacco, alcohol and binge drinking and more frequent sport
      than Spanish students and receive higher scores on the SF-36. Disinhibition is a
      risk factor for alcohol consumption and physical inactivity and SSS-V for tobacco
      consumption. CONCLUSIONS: The consumption of alcohol, tobacco and physical
      inactivity in universities in Spain and Mexico is low. The SSS-V full scale is a
      predictor of tobacco consumption and dimension DES of alcohol consumption and
      physical inactivity.

PMID- 25946532
TI  - [Characterization of hemodynamic ex vivo model to study endothelial activation by
      TNF-alpha in prefunded human veins].
AB  - Inflammation is recognized as part of the etiology of numerous diseases. The
      interaction among cells of the immunological system with local cells and
      molecules, such as cytokines and chemokines, allows cellular activation and
      response amplification. The importance of several physicochemical factors like
      frictional force, vascular flow, shear stress, and pressure is now recognized
      because they are known to modulate genetic expression and endothelial activation;
      however, there are very few studies that recreate such cellular
      microenvironments. Hence, it is of paramount importance to develop new models
      that will mimic physiological conditions. Our aim was to improve a human vein ex
      vivo model that would allow endothelial activation in flow conditions, to study
      the molecular components during adhesion, taking into consideration
      physicochemical parameters such as flow and shear stress. Endothelial umbilical
      human vein was used and activated with TNF-a in order to determine U937 monocytic
      cells adhesion, as well as cytokines secretion and ICAM-1 expression. This model
      will allow leukocyte adhesion studies, using different inflammatory stimulus,
      along with the signaling pathways involved in several pathologies.

PMID- 25946533
TI  - [Relation of leptin in plasma with oxidative damage in indigenous tepehuan and
      mestizo populations from Durango].
AB  - BACKGROUND: Obesity is a multifactorial metabolic disorder that involves lipid
      peroxidation (LPX), activating the antioxidant systems to counteract cellular
      damage. Objective: To evaluate the correlation between the antioxidant capacity
      and LPX levels of /eptin, in indigenous Tepehuan and Mestizo populations of the
      State of Durango. METHODS: We conducted a nutritional clinical study and lipid
      profile to confirm the state of health of a group of 60 indigenous Tepehuan of
      Mezquital and 68 mestizos subjects of Durango city, aged between 18 to 59 years.
      We determined the concentrations of leptin, antioxidant capacity and LPX in
      fasting conditions on plasma of participants, comparing averages, minimum,
      maximum, and standard deviation through ANOVA and Kruskai-Wal/is. For the
      correlation of variables, Pearson test was applied, getting the r value. RESULTS:
      Leptin levels were lower in indigenous Tepehuan than mestizos independent of body
      mass index. Mestizo subjects and Tepehuan with overweight and obesity (OW/0) or
      both ethnic groups show a greater degree of LPX (3.39 +/- 0.31, 2.72 +/- 0.54 MDA
      J.lmol/1, respectively; p < 0.05); however, OW/0 mestizos show more activation of
      its (0.37+/-0. 03 meqltrolox) than Tepehuan normal weight (NW) and OW/0 (0.32 +/
      0. 01 meq/trolox). The correlation between antioxidant capacity and LPX in mixed
      OW/0 was positive (r = 0.9; p < 0. 001). There is a correlation between levels of
      leptin and the antioxidant capacity of Tepehuan subjects both NW and OW/0 (r =
      0.40; p < 0.05 and r = -0.66; p < 0.0001, respectively). CONCLUSION: Tepehuan
      groups with OW/0 have less oxidative damage, while antioxidant mechanisms have a
      smaller activation than the top crosses of the same nutritional condition. The
      results suggest that antioxidant capacity has an implication on the regulation of
      leptin levels in Tepehuan subjects.

PMID- 25946534
TI  - [Efficacy and safety of ciprofloxacin treatment in urinary tract infections
      (UTIs) in adults: a systematic review with meta-analysis].
AB  - OBJECTIVES AND DESIGN: A systematic review with meta-analysis of randomized
      controlled trials (RGT) on the efficacy and safety of ciprofloxacin in the
      treatment of acute or complicated urinary tract infections in adults. Primary
      outcomes were bacteriological eradication, clinical cure, bacterial resistance,
      and adverse event rates. RESULTS: Initially, 111 RGTs were identified. We
      excluded 81 studies due to low quality methodology. An analysis of the remaining
      RGTs identified therapeutic equivalence of ciprofloxacin against other
      antimicrobials in terms of bacterial eradication and clinical cure at the end of
      treatment and in subsequent stages. The percentage of bacterial resistance was
      similar in both groups, while the percentage of related adverse events was
      significantly lower in the groups treated with ciprofloxacin. CONCLUSIONS: We
      conclude that ciprofloxacin is a safe and effective therapeutic alternative for
      the treatment of acute or complicated urinary tract infections in adults.

PMID- 25946535
TI  - [Nutritional approaches to modulate oxidative stress that induce Alzheimer's
      disease. Nutritional approaches to prevent Alzheimer's disease].
AB  - Alzheimer's disease is the most common cause of dementia in the world; symptoms
      first appear after age 65 and have a progressive evolution. Expecting an increase
      on its incidence and knowing there is currently no cure for Alzheimer's disease,
      it is a necessity to prevent progression. The change in diet due to globalization
      may explain the growth of the incidence in places such as Japan and Mediterranean
      countries, which used to have fewer incidences. There is a direct correlation
      between disease progression and the increased intake of alcohol, saturated fats,
      and red meat. Therefore, we find obesity and higher serum levels in cholesterol
      due to saturated fat as a result. A way to decrease the progression of
      Alzheimer's is through a diet rich in polipheno/es (potent antioxidants),
      unsaturated fats (monounsaturated and polyunsaturated), fish, vegetable fa t,
      fruits with low glycemic index, and a moderate consumption of red wine. Through
      this potent antioxidant diet we accomplish the prevention of dementia and the
      progression of Alzheimer's disease. This article emphasizes the food and other
      components that have been demonstrated to decrease the oxidative stress related
      to these progressive diseases.

PMID- 25946537
TI  - [Male aged 31 years with polyneuropathy, prostration, and hypogonadism].
AB  - We present the case of a 31 year-old male patient, who presented polyneuropathy,
      symmetrical, ascending, and progressive, that led to prostration of eight months
      duration, accompanied by hypogonadism, hypothyroidism, hyperprolactinemia, and
      the presence of multiple erythematous nodules on the skin. The MRI showed
      hypointense lesions in the vertebrae T-6 and L-4 with sclerotic appearance. The
      bone marrow biopsy reported the presence of 12% plasma cells with A. restriction,
      supporting monoclonal gammopathy (plasmocytoma).

PMID- 25946536
TI  - [Eczema herpeticum in a patient with atopic dermatitis, carrying r501x and
      2282del4 filaggrin null mutations].
AB  - Eczema herpeticum is an acute dermatoses caused by herpes simplex virus type 1 in
      atopic dermatitis patients, and is considered a dermatology emergency. Eczema
      herpeticum occurs in less than 3% of atopic patients. We report a patient with a
      history of atopic dermatitis who presented to an emergency department with eczema
      herpeticum. He was admitted and treated with antiviral medications with good
      outcome. We investigated filaggrin null mutations in the patient and his family
      and correlate them with the severity of the disease. We present the first Mexican
      patient with eczema herpeticum, atopic dermatitis and the presence of R501 X and
      2282del4 filaggrin null mutations.

PMID- 25946538
TI  - [Auscultation of the heart: an art on the road to extinction].
AB  - Auscultation of the heart is a clinical art that allows the doctor to make
      accurate diagnoses with the skills after formal training. The technology
      efficiently complements the clinical diagnosis, so that the latter is
      insufficient without a clinical approach; on the other hand, when the clinical
      practice is replaced by technology, diagnosis and treatment is equally
      ineffective. The cult of technology has led to the gradual/ass of the ability of
      cardiac auscultation, and the doctor has lost a powerful tool with diagnostic
      potential.

PMID- 25946539
TI  - [The skin as a vehicle for gene therapy: hemophilia B, an application model].
AB  - Artificial skin offers important advantages in gene therapy tor its biosafety and
      simple monitoring. An easy access of keratinocytes through small biopsies and
      their in vitro expansion enriched with epithelial stem cells, make them an ideal
      target for long-term therapeutic transgene expression. Corrective cutaneous gene
      therapy has been recently applied in clinical trials on dermatological genetic
      diseases. In systemic monogenic diseases such as hemophilia B, the graft of
      genetically modified skin in murine experimental models has achieved a modest
      increase of clotting factor IX in plasma that may attenuate severe symptoms of
      the disease.

PMID- 25946540
TI  - [Clinical and molecular findings of pachyonychia congenita type 2 (PC-2)].
AB  - Pachyonychia congenita is a group of autosomal dominant inheritance pattern
      disorders characterized by hypertrophic nail dystrophy There are two main
      clinical subtypes: type 1 and 2. Pachyonychia congenita type 2 is readily
      differentiated from type 1 by multiple steatocysts and/or presence of natal teeth
      and can be confirmed by mutations of KRT6B and KRT17. We report the case of a 33
      year-o/d female patient with the missense mutation in KRT17 gene (c.280C> T,
      p.Arg94Cys) and discuss the several clinical features found with this mutation in
      the literature.

PMID- 25946541
TI  - [Ideological conflicts leading to regulation of investigation with embryonic stem
      cells].
AB  - Human stem cells, particularly embryonic, have huge therapeutic potential to many
      degenerative diseases, so they are the subject of intense research in many
      countries. Because obtaining human stem cells involves the use of zygotes
      obtained by in vitro fertilization, when they arrive in the blastocyst stage,
      ethical issues arise that some groups considered insurmountable; in Mexico to
      date it has not been possible to established a law or rule that regulates the
      issue. The purpose of this paper is to discuss the ideological conflicts that
      have led to this situation, and about the light a judgment delivered by the Inter
      American Court of Human Rights may shed on a democratic and secular legislation.

PMID- 25946542
TI  - [The strategic purchasing of health services: a big opportunity for the National
      Universal Health System].
AB  - proposed to establish a service packages, whether through a single obligatory
      list or through the definition of a flexible, high priority set to be offered to
      specific populations according to their economic possibilities. For the strategic
      purchasing of services, two alternatives are proposed: to assign the fund either
      to a single national manager or to each of the existing public provider
      institutions, with the expectation that they would contract across each other and
      with private providers to fulfill their complementary needs.The proposal does not
      consider the risks and alternatives to a single tax contribution fund, which
      could have been suggested given that it is not an essential part of a National
      Universal Health System. However, it is necessary to discuss in more detail the
      roles and strategies for a national single-payer, especially for the strategic
      purchasing of high-cost and specialized interventions in the context of public
      and private providers. The alternative of allocating funds directly to providers
      would undermine the incentives for competition and collaboration and the capacity
      to steer providers towards the provision of high quality health services.It is
      proposed to focus the discussion of the reform of the national health system
      around strategic purchasing and the functions and structure of a single-payer as
      well as of agencies to articulate integrated health service networks as tools to
      promote quality and efficiency of the National Universal Health System. The
      inclusion of economic incentives to providers will be vital for competition, but
      also for the cooperation of providers within integrated, multi-institutional
      health service networks.Health professionals and sector policy specialists
      coordinated by the Centro de Estudios Espinosa Yglesi as in Mexico propose a
      policy to anchor the health system in primary care centered on the individual.
      The vision includes effective stewardship,solid financing, and the provision of
      services by a plurality of providers - including eventually those in the private
      sector. A unified approach to financing health through a unique, exclusively tax
      based fund would be established. Alternatives are

PMID- 25946543
TI  - [Commentary on the Nobel Prize that has been granted in Medicine-Physiology,
      Chemistry and Physics to noteable investigators].
AB  - The Nobel Prize was established by Alfred Nobel in 1901 to award people who have
      made outstanding achievements in physics, chemistry and medicine. So far, from
      852 laureates, 45 have been female. Marie Curie was the first woman to receive
      the Nobel Prize in 1903 for physics and eight years later also for chemistry It
      is remarkable that her daughter Irene and her husband also received the Nobel
      Prize for chemistry in 1935. Other two married couples, Cori and Moser, have also
      been awarded the Nobel Prize. The present commentary attempts to show the female
      participation in the progress of scientific activities.

PMID- 25946544
TI  - Evaluation of Cr(VI) Exposed and Unexposed Plant Parts of Tradescantia pallida
      (Rose) D. R. Hunt. for Cr Removal from Wastewater by Biosorption.
AB  - Phytoremediation is an efficient method for the removal of heavy metals from
      contaminated systems. A productive disposal of metal accumulating plants is a
      major concern in current scenario. In this work, Cr(VI) accumulating Tradescantia
      pallida plant parts were investigated for its reuse as a biosorbent for the
      removal of Cr(VI) ions. The effect of pH, contact time, sorbent dosage, Cr(VI)
      concentration and temperature was examined to optimize these process parameters.
      Results showed that Cr(VI) exposed/unexposed T. pallida leaf biomass could remove
      94% of chromium with a sorption capacity of 64.672 mg g(-1). Whereas the kinetics
      of Cr(VI) biosorption was well explained by the pseudo second-order kinetic
      model, the Langmuir model better described the data on Cr(VI) sorption isotherm
      compared with the Freundlich model. The changes in the free energy (DeltaG
      degrees ), entropy (DeltaS degrees ) and enthalpy (DeltaH degrees ) were found to
      be -5.276 kJ mol(-1), 0.391 kJ mol(-1) K(-1) and 11.346 kJ mol(-1), respectively,
      which indicated the process to be spontaneous, feasible and endothermic in
      nature. FTIR spectra of T. pallida leaf biomass revealed the active participation
      of ligands, such as -NH, amide, hydroxyl and sulphonate groups present in the
      biomass for Cr(VI) binding, SEM analysis revealed a porous structure of the
      biosorbent for an easy uptake of Cr(VI). 

PMID- 25946548
TI  - A Novel Exfoliation Strategy to Significantly Boost the Energy Storage Capability
      of Commercial Carbon Cloth.
AB  - A facile and efficient electrochemical oxidation method to directly activated
      carbon cloth as an excellent electrode material for supercapacitors is reported.
      Flexible asymmetric supercapacitor devices based on activated carbon cloth anodes
      reach a remarkable energy density and excellent long-term durability. 

PMID- 25946547
TI  - Volumetric spiral chemical shift imaging of hyperpolarized [2-(13) c]pyruvate in
      a rat c6 glioma model.
AB  - PURPOSE: MRS of hyperpolarized [2-(13)C]pyruvate can be used to assess multiple
      metabolic pathways within mitochondria as the (13)C label is not lost with the
      conversion of pyruvate to acetyl-CoA. This study presents the first MR
      spectroscopic imaging of hyperpolarized [2-(13)C]pyruvate in glioma-bearing
      brain. METHODS: Spiral chemical shift imaging with spectrally undersampling
      scheme (1042 Hz) and a hard-pulse excitation was exploited to simultaneously
      image [2-(13)C]pyruvate, [2-(13)C]lactate, and [5-(13)C]glutamate, the
      metabolites known to be produced in brain after an injection of hyperpolarized [2
      (13)C]pyruvate, without chemical shift displacement artifacts. A separate
      undersampling scheme (890 Hz) was also used to image [1-(13)C]acetyl-carnitine.
      Healthy and C6 glioma-implanted rat brains were imaged at baseline and after
      dichloroacetate administration, a drug that modulates pyruvate dehydrogenase
      kinase activity. RESULTS: The baseline metabolite maps showed higher lactate and
      lower glutamate in tumor as compared to normal-appearing brain. Dichloroacetate
      led to an increase in glutamate in both tumor and normal-appearing brain.
      Dichloroacetate-induced %-decrease of lactate/glutamate was comparable to the
      lactate/bicarbonate decrease from hyperpolarized [1-(13)C]pyruvate studies.
      Acetyl-carnitine was observed in the muscle/fat tissue surrounding the brain.
      CONCLUSION: Robust volumetric imaging with hyperpolarized [2-(13)C]pyruvate and
      downstream products was performed in glioma-bearing rat brains, demonstrating
      changes in mitochondrial metabolism with dichloroacetate.

PMID- 25946551
TI  - Bacillus phytases: Current status and future prospects.
AB  - Phytases catalyze the hydrolysis of phytic acid in a stepwise manner to lower
      inositol phosphates, myo-inositol (having important role in metabolism and signal
      transduction pathways), and inorganic phosphate. These enzymes have been widely
      used in animal feed in order to improve phosphorus nutrition and to decrease
      pollution in animal waste. Compared to previously described phytases, the phytase
      (PhyL) from Bacillus licheniformis ATCC 14580 has attractive biochemical
      properties which can increase the profitability of several biotechnological
      procedures (animal nutrition, humain health...etc). Due to its amino acid
      sequence with critical substitutions, the PhyL could be a model to enhance other
      phytases features, in terms of thermal stability and high activity. Otherwise, an
      engineered PhyL, with low pH optimum, will represent a challenge within the class
      of beta- propeller phytases. 

PMID- 25946553
TI  - H.h. Flor: pioneer in phytopathology.

PMID- 25946552
TI  - Epidemiology and molecular characteristics of norovirus GII.4 Sydney outbreaks in
      Taiwan, January 2012-December 2013.
AB  - In 2012, a new norovirus GII.4 variant (GII.4 Sydney) emerged and caused the
      majority of the acute gastroenteritis outbreaks in Australia, Asia, Europe, and
      North America. We examined the epidemiologic and molecular virologic
      characteristics of reported acute gastroenteritis outbreaks determined to be
      caused by norovirus in Taiwan from January 2012 to December 2013. A total of 253
      (45.7%) of 552 reported acute gastroenteritis outbreaks tested positive for
      norovirus, of which 165 (65.5%) were typed as GII.4 Sydney. GII.4 Sydney
      outbreaks were reported from all geographic areas of Taiwan and occurred most
      frequently in schools (35.8%) and long-term care facilities (24.2%). Person-to
      person transmission was identified in 116 (70.3%) of the outbreaks. Phylogenetic
      analyses of full-length ORF2 of eight specimens indicated that GII.4 Sydney
      strains detected in Taiwan were closely related to strains detected globally.
      Continued outbreak surveillance and strain typing are needed to provide
      information on epidemiologic and virologic trends of novel norovirus strains.

PMID- 25946554
TI  - CCL20 and IL22 Messenger RNA Expression After Adalimumab vs Methotrexate
      Treatment of Psoriasis: A Randomized Clinical Trial.
AB  - IMPORTANCE: Methotrexate is a first-line systemic agent for treating of
      psoriasis, although its onset of effects is slower and overall it is less
      effective than tumor necrosis factor blockers. OBJECTIVE: To differentiate the
      response of psoriatic disease to adalimumab and methotrexate sodium. DESIGN,
      SETTING, AND PARTICIPANTS: Single-center, randomized, assessor-blind, 2-arm
      clinical trial of 30 patients from the outpatient dermatology center of Tufts
      Medical Center, enrolled from August 18, 2009, to October 11, 2011. Patients aged
      18 to 85 years with chronic plaque-type psoriasis, a minimum Physician Global
      Assessment score of 3 (higher scores indicate more severe disease), and a
      psoriatic plaque of at least 2 cm were randomized in a 1:1 fashion to receive
      subcutaneous adalimumab or oral methotrexate. Skin biopsy specimens obtained at
      baseline and weeks 1, 2, 4, and 16 were given a histologic grade by blinded
      assessors to evaluate treatment response. Analyses were conducted from April 16,
      2013, to January 5, 2015. INTERVENTIONS: A 16-week course of subcutaneous
      adalimumab (40 mg every 2 weeks after a loading dose) or low-dosage oral
      methotrexate sodium (7.5-25 mg/wk). MAIN OUTCOMES AND MEASURES: Changes in
      genomic, immunohistochemical, and messenger RNA (mRNA) profiles. RESULTS:
      Methotrexate responders experienced significant downregulation of helper T-cell
      related (T(H)1, T(H)17, and T(H)22) mRNA expression compared with methotrexate
      nonresponders. Comparisons among adalimumab-treated patients were limited by the
      number of nonresponders (n = 1). Between adalimumab and methotrexate responders,
      we found no significant differences in gene expression at any study point or in
      the expression of T-cell-related mRNA at week 16. Adalimumab responders
      demonstrated early downregulation of chemokine (C-C motif) ligand 20 (CCL20) mRNA
      (mean [SE] at week 2, -1.83 [0.52], P < .001; week 16, -3.55 [0.54], P < .001)
      compared with late downregulation for methotrexate responders (week 2, 0.02
      [0.51], P = .96; week 16, -2.96 [0.51], P < .001). Similar differences were
      observed with interleukin 22 (IL22) mRNA showing early downregulation for
      adalimumab responders (week 2, -3.17 [1.00], P < .001; week 16, -3.58 [1.00], P <
      .001) compared with late downregulation for methotrexate responders (week 2, 
      0.44 [0.68], P = .64; week 16, -5.14 [0.68], P < .001). Analysis of variance
      findings for key mRNA and immunohistochemical marker expression over the study
      course were significant only for CCL20 (P = .03) and IL22 (P = .006) mRNA
      comparing adalimumab and methotrexate responders. CONCLUSIONS AND RELEVANCE:
      Methotrexate is an immunomodulator with effects on helper T-cell signaling in
      psoriasis. Similar genomic and immunohistochemical response signatures and levels
      of mRNA downregulation at study completion among adalimumab and methotrexate
      responders suggest a disease-driven instead of therapeutic-driven pathway
      regulation. Adalimumab and methotrexate responses are differentiated by patterns
      of normalization of CCL20 and IL22 mRNA expression and may explain the varied
      onset and degree of clinical responses by each treatment. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00932113.

PMID- 25946555
TI  - Effective Immobilization of Agrobacterium sp. IFO 13140 Cells in Loofa Sponge for
      Curdlan Biosynthesis.
AB  - Curdlan production by Agrobacterium sp. IFO13140 immobilized on loofa sponge,
      alginate and loofa sponge with alginate was investigated. There was no
      statistically-significant difference in curdlan production when the microorganism
      was immobilized in different matrices. The loofa sponge was chosen because of its
      practical application and economy and because it provides a high stability
      through its continued use. The best conditions for immobilization on loofa sponge
      were 50 mg of cell, 200 rpm and 72 h of incubation, which provided a curdlan
      production 1.50-times higher than that obtained by free cells. The higher
      volumetric productivity was achieved by immobilized cells (0.09 g/L/h) at 150
      rpm. The operating stability was evaluated, and until the fourth cycle,
      immobilized cells retained 87.40% of the production of the first cycle. The
      immobilized cells remained active after 300 days of storage at 4  degrees C. The
      results of this study demonstrate success in immobilizing cells for curdlan
      biosynthesis, making the process potentially suitable for industrial scale-up.
      Additional studies may show a possible contribution to the reduction of operating
      costs. 

PMID- 25946556
TI  - Investigating the Effect of Cold Soak Duration on Phenolic Extraction during
      Cabernet Sauvignon Fermentation.
AB  - The impact of increasing cold soak (CS) duration (0, 1, 4, 7, and 10 days at 10 
      degrees C) on the extraction of phenolic compounds during the CS period and
      primary fermentation as well as the final composition of Cabernet Sauvignon wine
      was investigated. The results showed that CS duration had no effect on
      hydroxycinnamate and flavonol extractions. Greater amounts of gallic acid, (+)
      catechin, (-)-epicatechin, and total tannins were extracted with increasing CS
      duration, with differences maintained during bottle aging. Anthocyanin extraction
      and color density increased with longer periods of CS; however, by the end of
      primary fermentation, as well as three months' bottle aging, there were no
      significant differences due to CS duration. The wines made with seven and 10 days
      of CS had higher seed tannin contributions and total tannin compared to the non
      CS wine, which could potentially result in increased astringency. 

PMID- 25946557
TI  - Chemical Composition and Insecticidal Activity of Essential Oils from Zanthoxylum
      dissitum Leaves and Roots against Three Species of Storage Pests.
AB  - This work aimed to investigate chemical composition of essential oils obtained
      from Zanthoxylum dissitum leaves and roots and their insecticidal activities
      against several stored product pests, namely the cigarette beetle (Lasioderma
      serricorne), red flour beetle (Tribolium castaneum) and black carpet beetle
      (Attagenus piceus). The analysis by GC-MS of the essential oils allowed the
      identification of 28 and 22 components, respectively. It was found that
      sesquiterpenoids comprised a fairly high portion of the two essential oils, with
      percentages of 74.0% and 80.9% in the leaves and roots, respectively. The main
      constituents identified in the essential oil of Z. dissitum leaves were delta
      cadinol (12.8%), caryophyllene (12.7%), beta-cubebene (7.9%), 4-terpineol (7.5%)
      and germacrene D-4-ol (5.7%), while humulene epoxide II (29.4%), caryophyllene
      oxide (24.0%), diepicedrene-1-oxide (10.7%) and Z,Z,Z-1,5,9,9-tetramethyl-1,4,7
      cycloundecatriene (8.7%) were the major components in the essential oil of Z.
      dissitum roots. The insecticidal activity results indicated that the essential
      oil of Z. dissitum roots exhibited moderate contact toxicity against three
      species of storage pests, L. serricorne,T. castaneum and A. piceus, with LD50
      values of 13.8, 43.7 and 96.8 ug/adult, respectively. 

PMID- 25946558
TI  - NBM-T-BBX-OS01, Semisynthesized from Osthole, Induced G1 Growth Arrest through
      HDAC6 Inhibition in Lung Cancer Cells.
AB  - Disrupting lung tumor growth via histone deacetylases (HDACs) inhibition is a
      strategy for cancer therapy or prevention. Targeting HDAC6 may disturb the
      maturation of heat shock protein 90 (Hsp90) mediated cell cycle regulation. In
      this study, we demonstrated the effects of semisynthesized NBM-T-BBX-OS01 (TBBX)
      from osthole on HDAC6-mediated growth arrest in lung cancer cells. The results
      exhibited that the anti-proliferative activity of TBBX in numerous lung cancer
      cells was more potent than suberoylanilide hydroxamic acid (SAHA), a clinically
      approved pan-HDAC inhibitor, and the growth inhibitory effect has been mediated
      through G1 growth arrest. Furthermore, the protein levels of cyclin D1, CDK2 and
      CDK4 were reduced while cyclin E and CDK inhibitor, p21Waf1/Cip1, were up
      regulated in TBBX-treated H1299 cells. The results also displayed that TBBX
      inhibited HDAC6 activity via down-regulation HDAC6 protein expression. TBBX
      induced Hsp90 hyper-acetylation and led to the disruption of cyclin D1/Hsp90 and
      CDK4/Hsp90 association following the degradation of cyclin D1 and CDK4 proteins
      through proteasome. Ectopic expression of HDAC6 rescued TBBX-induced G1 arrest in
      H1299 cells. Conclusively, the data suggested that TBBX induced G1 growth arrest
      may mediate HDAC6-caused Hsp90 hyper-acetylation and consequently increased the
      degradation of cyclin D1 and CDK4. 

PMID- 25946559
TI  - Silver(I) 2,2'-(1,2-Phenylenedisulfanediyl)diacetic Acid as a Molecular Building
      Block for a Silver(I)-Cadmium(II) Coordination Polymer.
AB  - Starting from heterotopic multidentate ligand 2,2'-(1,2
      phenylenedisulfanediyl)diacetic acid, (RS,RS,RS,RS/SS,SS,SS,SS)-[Ag{1,2
      C6H4(SCH2COOH)2-kappa2S,S'}2]BF4 (1) was prepared and further used as a building
      block for the synthesis of heterobimetallic Ag-Cd coordination polymer
      [Ag2Cd2{1,2-(OOCCH2S)2C6H4}3 (H2O)3.5H2O]n (2). Both complexes were characterized
      by X-ray structure analysis and conventional spectroscopic techniques. 

PMID- 25946560
TI  - Fluorescent filter-trap assay for amyloid fibril formation kinetics in complex
      solutions.
AB  - Amyloid fibrils are the most distinct components of the plaques associated with
      various neurodegenerative diseases. Kinetic studies of amyloid fibril formation
      shed light on the microscopic mechanisms that underlie this process as well as
      the contributions of internal and external factors to the interplay between
      different mechanistic steps. Thioflavin T is a widely used noncovalent
      fluorescent probe for monitoring amyloid fibril formation; however, it may suffer
      from limitations due to the unspecific interactions between the dye and the
      additives. Here, we present the results of a filter-trap assay combined with the
      detection of fluorescently labeled amyloid beta (Abeta) peptide. The filter-trap
      assay separates formed aggregates based on size, and the fluorescent label
      attached to Abeta allows for their detection. The times of half completion of the
      process (t1/2) obtained by the filter-trap assay are comparable to values from
      the ThT assay. High concentrations of human serum albumin (HSA) and carboxyl
      modified polystyrene nanoparticles lead to an elevated ThT signal, masking a
      possible fibril formation event. The filter-trap assay allows fibril formation to
      be studied in the presence of those substances and shows that Abeta fibril
      formation is kinetically inhibited by HSA and that the amount of fibrils formed
      are reduced. In contrast, nanoparticles exhibit a dual-behavior governed by their
      concentration. 

PMID- 25946561
TI  - Performance breakdown in optimal stimulus decoding.
AB  - OBJECTIVE: One of the primary goals of neuroscience is to understand how neurons
      encode and process information about their environment. The problem is often
      approached indirectly by examining the degree to which the neuronal response
      reflects the stimulus feature of interest. APPROACH: In this context, the methods
      of signal estimation and detection theory provide the theoretical limits on the
      decoding accuracy with which the stimulus can be identified. The Cramer-Rao lower
      bound on the decoding precision is widely used, since it can be evaluated easily
      once the mathematical model of the stimulus-response relationship is determined.
      However, little is known about the behavior of different decoding schemes with
      respect to the bound if the neuronal population size is limited. MAIN RESULTS: We
      show that under broad conditions the optimal decoding displays a threshold-like
      shift in performance in dependence on the population size. The onset of the
      threshold determines a critical range where a small increment in size, signal-to
      noise ratio or observation time yields a dramatic gain in the decoding precision.
      SIGNIFICANCE: We demonstrate the existence of such threshold regions in early
      auditory and olfactory information coding. We discuss the origin of the threshold
      effect and its impact on the design of effective coding approaches in terms of
      relevant population size.

PMID- 25946562
TI  - Utilizing 19F NMR to investigate drug disposition early in drug discovery.
AB  - 1. Nuclear magnetic resonance (NMR), a non-selective and inherently quantitative
      method, has not been widely used as a quantitative tool for characterizing the
      disposition of lead molecules prior to clinical development. As a test case, we
      have chosen a fluoropyrimidine compound in lead optimization phase and evaluated
      its disposition following oral administration to rats using 19F NMR. 2. Urine,
      bile and feces from individual rats were profiled and the amount of dose
      eliminated in each matrix was calculated. The results indicated that, in male
      rats, the mean dose eliminated over 0-48 h was 40%, with 28% in urine, 9% in bile
      and 3% in feces. In female rats, the mean dose recovered in excreta over the same
      period was 55%, with 40% in urine, 8% in bile and 7% in feces. 3. In addition,
      plasma from rats and plasma from toxicology study in dogs were also profiled and
      exposure of circulating entities was determined. Plasma exposure determined by
      19F NMR was in good agreement with those determined by conventional LC-MS/MS
      method, suggesting quantitative 19F NMR can be reliably used to estimate single
      dose or steady-state systemic exposure of circulating entities in animals and
      humans.

PMID- 25946563
TI  - Synthesis of Polycyclic Nitrogen Heterocycles via Cascade Pd-Catalyzed Alkene
      Carboamination/Diels-Alder Reactions.
AB  - Cascade Pd-catalyzed alkene carboamination/Diels-Alder reactions between
      bromodienes and amines bearing two pendant alkenes are described. These
      transformations generate 4 bonds, 3 rings, and 3-5 stereocenters to afford
      polycyclic nitrogen heterocycles with high diastereoselectivity. 

PMID- 25946565
TI  - Individualizing treatment for patients with nasopharyngeal cancer.

PMID- 25946564
TI  - The SUMO deconjugating peptidase Smt4 contributes to the mechanism required for
      transition from sister chromatid arm cohesion to sister chromatid pericentromere
      separation.
AB  - The pericentromere chromatin protrudes orthogonally from the sister-sister
      chromosome arm axis. Pericentric protrusions are organized in a series of loops
      with the centromere at the apex, maximizing its ability to interact with
      stochastically growing and shortening kinetochore microtubules. Each
      pericentromere loop is ~50 kb in size and is organized further into secondary
      loops that are displaced from the primary spindle axis. Cohesin and condensin are
      integral to mechanisms of loop formation and generating resistance to outward
      forces from kinesin motors and anti-parallel spindle microtubules. A major
      unanswered question is how the boundary between chromosome arms and the
      pericentromere is established and maintained. We used sister chromatid separation
      and dynamics of LacO arrays distal to the pericentromere to address this issue.
      Perturbation of chromatin spring components results in 2 distinct phenotypes. In
      cohesin and condensin mutants sister pericentric LacO arrays separate a defined
      distance independent of spindle length. In the absence of Smt4, a peptidase that
      removes SUMO modifications from proteins, pericentric LacO arrays separate in
      proportion to spindle length increase. Deletion of Smt4, unlike depletion of
      cohesin and condensin, causes stretching of both proximal and distal
      pericentromere LacO arrays. The data suggest that the sumoylation state of
      chromatin topology adjusters, including cohesin, condensin, and topoisomerase II
      in the pericentromere, contribute to chromatin spring properties as well as the
      sister cohesion boundary. 

PMID- 25946566
TI  - Laparoscopic Interrupted Muscular Arch Repair in Recurrent Unilateral Inguinal
      Hernia Among Children.
AB  - PURPOSE: We present a procedure of suturing the transversus abdominis muscular
      arch to the ileopubic tract laparoscopically in order to repair recurrent
      unilateral pediatric inguinal hernia (PIH). PATIENTS AND METHODS: Twenty-five
      children with recurrent unilateral PIH were treated during a 5-year period in a
      tertiary academic center. All cases were subjected to laparoscopic hernia repair
      and discharged the next morning. Sutures were placed from the muscular arch to
      the ileopubic tract, avoiding the spermatic vessels and duct, in an interrupted
      manner using 2/0-3/0 polypropylene (Prolene(r); Ethicon, Somerville, NJ) or
      polyglactin 910 (Vicryl(r); Ethicon) sutures. In 4 cases, a rectangular purse
      string-like suture was added to narrow the internal ring defect. Operative
      findings and postoperative results and complications were assessed. The patients
      were followed up for a period that ranged between 6 and 60 months. RESULTS: There
      were 23 boys and 2 girls. Operative age ranged between 18 months and 15 years.
      Three or four sutures were placed in each case. In 4 cases, an additional
      rectangular purse-string-like suture was added. Operative time ranged between 35
      and 70 minutes, and there was no conversion. Mild scrotal edema was reported in 4
      cases and port-site infection in 2 cases; all cases were treated conservatively.
      One case of recurrence among boys was reported, but there was no case of
      testicular atrophy. Cosmetic outcomes were excellent. CONCLUSIONS: Laparoscopic
      interrupted muscular arch repair is a feasible and safe technique in the
      reconstruction of the inguinal canal in recurrent unilateral PIH. Larger studies
      and long-term follow-up are needed to support our encouraging results.

PMID- 25946567
TI  - Development of a Sandwich ELISA for Quantification of Gly m 4, a Soybean
      Allergen.
AB  - Gly m 4 is a key soybean allergen that causes allergic symptoms in the skin,
      gastrointestinal tract, or respiratory tract of sensitive individuals. To
      understand naturally variable levels of Gly m 4 among conventional soybean
      varieties, a sandwich ELISA was developed and validated using a mouse anti-Gly m
      4 monoclonal antibody and a goat anti-Gly m 4 polyclonal antibody as capture and
      detection antibodies, respectively. The ELISA shows high specificity to Gly m 4
      without any cross-reactivity to other soybean proteins and has a quantification
      range of 7.8-250 ng/mL using an Escherichia coli-produced recombinant Gly m 4,
      with 2.1 ng/mL being the limit of detection. Within the quantification range, the
      coefficients of variation of the intra-assay and interassay precision are less
      than 5 and 12%, respectively. Moreover, extraction efficiency and dilutional
      parallelism experiments were completed to demonstrate the assay is accurate. The
      validated assay was used to quantify Gly m 4 levels in 128 soybean samples from
      24 conventional soybean varieties grown at 8 distinct geographical locations.
      There was a 13-fold difference between the least and greatest amounts of Gly m 4
      concentrations among the samples, and the results demonstrate that the most
      significant sources of variability in Gly m 4 levels in the conventional
      varieties were related to location and variety. 

PMID- 25946568
TI  - IBD LIVE Case Series-Case 2: Previous Cancer in a Patient with Crohn's Disease:
      Is It Appropriate to Use Biologics and Immunosuppressants for IBD Treatment?

PMID- 25946569
TI  - Reduced Numbers and Proapoptotic Features of Mucosal-associated Invariant T Cells
      as a Characteristic Finding in Patients with Inflammatory Bowel Disease.
AB  - BACKGROUND: Mucosal-associated invariant T (MAIT) cells are innate-like T cells
      involved in the homeostasis of mucosal immunity; however, their role in
      inflammatory bowel disease (IBD) is unclear. METHODS: Flow cytometry was used to
      enumerate peripheral blood MAIT cells in 88 patients with ulcerative colitis
      (UC), 68 with Crohn's disease (CD), and in 57 healthy controls.
      Immunohistochemistry identified MAIT cells in intestinal tissue samples from
      patients with UC (n = 5) and CD (n = 10), and in control colon (n = 5) and small
      intestine (n = 9) samples. In addition, expression of activated caspases by MAIT
      cells in the peripheral blood of 14 patients with UC and 15 patients with CD, and
      16 healthy controls was examined. RESULTS: Peripheral blood analysis revealed
      that patients with IBD had significantly fewer MAIT cells than healthy controls
      (P < 0.0001). The number of MAIT cells in the inflamed intestinal mucosae of
      patients with UC and CD was also lower than that in control mucosae (P = 0.0079
      and 0.041, respectively). The number of activated caspase-expressing MAIT cells
      in the peripheral blood of patients with UC and CD was higher than that in
      healthy controls (P = 0.0061 and 0.0075, respectively), suggesting that the
      reduced MAIT cell numbers in IBD are associated with an increased level of
      apoptosis among these cells. CONCLUSIONS: The number of MAIT cells in the
      peripheral blood and inflamed mucosae of patients with UC and CD was lower than
      that in non-IBD controls. Also, MAIT cells from patients with IBD exhibited
      proapoptotic features. These data suggest the pathological involvement and the
      potential for therapeutic manipulation of these cells in patients with IBD.

PMID- 25946570
TI  - Aging, Tolerance to High Altitude, and Cardiorespiratory Response to Hypoxia.
AB  - Richalet, Jean-Paul, and Francois J. Lhuissier. Aging, tolerance to high
      altitude, and cardiorespiratory response to hypoxia. High Alt Med Biol. 16:117
      124, 2015.--It is generally accepted that aging is rather protective, at least at
      moderate altitude. Some anecdotal reports even mention successful ascent of peaks
      over 8000 m and even Everest by elderly people. However, very few studies have
      explored the influence of aging on tolerance to high altitude and prevalence of
      acute high altitude related diseases, taking into account all confounding factors
      such as speed of ascent, altitude reached, sex, training status, and chemo
      responsiveness. Changes in physiological responses to hypoxia with aging were
      assessed through a cross-sectional 20-year study including 4675 subjects (2789
      men, 1886 women; 14-85 yrs old) and a longitudinal study including 30 subjects
      explored at a mean 10.4-year interval. In men, ventilatory response to hypoxia
      increased, while desaturation was less pronounced with aging. Cardiac response to
      hypoxia was blunted with aging in both genders. Similar results were found in the
      longitudinal study, with a decrease in cardiac and an increase in ventilatory
      response to hypoxia with aging. These adaptive responses were less pronounced or
      absent in post-menopausal untrained women. In conclusion, in normal healthy and
      active subjects, aging has no deleterious effect on cardiac and ventilatory
      responses to hypoxia, at least up to the eighth decade. Aging is not a
      contraindication for high altitude, as far as no pathological condition
      interferes and physical fitness is compatible with the intensity of the expected
      physical demand of one's individual. Physiological evaluation through hypoxic
      exercise testing before going to high altitude is helpful to detect risk factors
      of severe high altitude-related diseases.

PMID- 25946572
TI  - Audit of allied health assistant roles: suggestions for improving quality in
      rural settings.
AB  - PROBLEM: There is considerable potential for allied health assistant roles to
      address rural workforce shortage, but there is also a need to ensure quality of
      these roles. DESIGN: A total of 41 allied health assistant trial roles were
      audited using an intensive onsite audit by independent clinicians. SETTING:
      Queensland public health services across rural/regional and metropolitan
      settings. KEY MEASURES FOR IMPROVEMENT: Audit ratings of rural/regional and
      metropolitan positions were compared on indicators of training, supervision,
      performance, duties and scope of practice as measured through multiple sources.
      STRATEGIES FOR CHANGE: Appropriately targeted in-service training may facilitate
      more effective utilisation of rural allied health assistants. EFFECTS OF CHANGE:
      Metropolitan and rural/regional audits showed consistency across qualifications,
      provision of duty statements and formal supervision arrangements. However, rural
      positions were not able to provide comparable levels of in-service training and
      supervision, and rural positions reflected a more restricted scope of practice.
      LESSONS LEARNT: Training in reflective practice may be a step to realising the
      potential of this crucial and emerging sector of the rural health workforce.

PMID- 25946571
TI  - Evidence of Kinetic Cooperativity in Dimeric Ketopantoate Reductase from
      Staphylococcus aureus.
AB  - Ketopantoate reductase (KPR) catalyzes the NADPH-dependent production of
      pantoate, an essential precursor in the biosynthesis of coenzyme A. Previous
      structural studies have been limited to Escherichia coli KPR, a monomeric enzyme
      that follows a sequential ordered mechanism. Here we report the crystal structure
      of the Staphylococcus aureus enzyme at 1.8 A resolution, the first description of
      a dimeric KPR. Using sedimentation velocity analysis, we show that the S. aureus
      KPR dimer is stable in solution. In fact, our structural analysis shows that the
      dimeric assembly we identify is present in the majority of KPR crystal
      structures. Steady state analysis of S. aureus KPR reveals strong positive
      cooperativity with respect to NADPH (Hill coefficient of 2.5). In contrast, high
      concentrations of the substrate ketopantoate (KP) inhibit the activity of the
      enzyme. These observations are consistent with a random addition mechanism in
      which the initial binding of NADPH is the kinetically preferred path. In fact,
      Forster resonance energy transfer studies of the equilibrium binding of NADPH
      show only a small degree of cooperativity between subunits (Hill coefficient of
      1.3). Thus, the apparently strong cooperativity observed in substrate saturation
      curves is due to a kinetic process that favors NADPH binding first. This
      interpretation is consistent with our analysis of the A181L substitution, which
      increases the Km of ketopantoate 844-fold, without affecting kcat. The crystal
      structure of KPRA181L shows that the substitution displaces Ser239, which is
      known to be important for the binding affinity of KP. The decrease in KP affinity
      would enhance the already kinetically preferred NADPH binding path, making the
      random mechanism appear to be sequentially ordered and reducing the kinetic
      cooperativity. Consistent with this interpretation, the NADPH saturation curve
      for KPRA181L is hyperbolic. 

PMID- 25946573
TI  - What is your diagnosis? Liver aspirate from a hypoglycemic dog.

PMID- 25946574
TI  - The Effect of Glenohumeral Internal-Rotation Deficit on Functional Rotator
      Strength Ratio in Adolescent Overhead Athletes.
AB  - CONTEXT: Glenohumeral (GH) internal-rotation deficit (GIRD) and lower eccentric
      external-rotator (ER) to concentric internal-rotator (IR) strength (ER:IR) ratio
      have been documented as risk factors for shoulder injuries, but there is no
      information on whether GIRD has an adverse effect on ER:IR ratio in adolescent
      overhead athletes. OBJECTIVES: The aim of this study was to investigate the
      effects of GIRD on functional ER:IR ratio of the adolescent overhead athletes.
      DESIGN: Cross-sectional study. SETTING: University research laboratory.
      PARTICIPANTS: 52 adolescent overhead athletes. MAIN OUTCOME MEASURES: To
      determine GIRD, the range of GH IR and ER motion was measured with a digital
      inclinometer. An isokinetic dynamometer was used to assess eccentric and
      concentric IR and ER muscle strength of the dominant and nondominant shoulders.
      One-way ANCOVA where sport type was set as a covariate was used to analyze the
      difference between athletes with and without GIRD. RESULTS: After standardized
      examinations of all shoulders, the athletes were divided into 2 groups, shoulders
      with (n = 27) and without GIRD (n = 25). There was a significant difference
      between groups in functional ER:IR ratio (P < .001). Athletes with GIRD had lower
      ER:IR ratio (0.56) than athletes without GIRD (0.83). CONCLUSIONS: As GIRD has an
      adverse effect on functional ratio of the shoulder-rotator muscles, interventions
      for adolescent overhead athletes should include improving GH-rotation range of
      motion.

PMID- 25946575
TI  - Wafer-scale synthesis of thickness-controllable MoS2 films via solution
      processing using a dimethylformamide/n-butylamine/2-aminoethanol solvent system.
AB  - The wafer-scale synthesis of two-dimensional molybdenum disulfide (MoS2) films,
      with high layer-controllability and uniformity, remains a significant challenge
      in the fields of nano and optoelectronics. Here, we report the highly thickness
      controllable growth of uniform MoS2 thin films on the wafer-scale via a spin
      coating route. Formulation of a dimethylformamide-based MoS2 precursor solution
      mixed with additional amine- and amino alcohol-based solvents (n-butylamine and 2
      aminoethanol) allowed for the formation of a uniform coating of MoS2 thin films
      over a 2 inch wafer-scale SiO2/Si substrate. In addition, facile control of the
      average number of stacking layers is demonstrated by simply manipulating the
      concentration of the precursor solution. Various characterization results reveal
      that the synthesized MoS2 film has wafer-scale homogeneity with excellent
      crystalline quality and a stoichiometric chemical composition. To further
      demonstrate possible device applications, a mostly penta-layered MoS2 thin film
      was integrated into a top-gated field-effect transistor as the channel layer and
      we also successfully transferred our films onto transparent/flexible substrates. 

PMID- 25946576
TI  - Carbetocin versus oxytocin for prevention of postpartum hemorrhage in obese
      nulliparous women undergoing emergency cesarean delivery.
AB  - OBJECTIVE: To assess and compare the effectiveness and safety of single IV polus
      dose of carbetocin, versus IV oxytocin infusion in the prevention of PPH in obese
      nulliparous women undergoing emergency Cesarean Delivery. METHODS: A double
      blinded randomized-controlled trial was conducted on 180 pregnant women with BMI
      >30. Women were randomized to receive either oxytocin or carbetocin during C.S.
      The primary outcome measure was major primary PPH >1000 ml within 24 h of
      delivery as per the definition of PPH by the World Health Organization Secondary
      outcome measures were hemoglobin and hematocrit changes pre- and post-delivery,
      use of further ecobolics, uterine tone 2 and 12-h postpartum and adverse effects.
      RESULTS: A significant difference in the amount of estimated blood loss or the
      incidence of primary postpartum haemorrhage (>1000 ml) in both groups.
      Haemoglobin levels before and 24-h postpartum was similar. None from the
      carbetocin group versus 71.5% in oxytocin group needed additional utrotonics (p <
      0.01). The uterine contractility was better in the carbetocin group at 2, and 12
      h postpartum (p < 0.05). CONCLUSIONS: A single 100-ug IV carbetocin is more
      effective than IV oxytocin infusion for maintaining adequate uterine tone and
      preventing postpartum bleeding in obese nulliparous women undergoing emergency
      cesarean delivery, both has similar safety profile and minor hemodynamic effect.

PMID- 25946577
TI  - Structural fluctuation governed dynamic diradical character in pentacene.
AB  - We unravel intriguing dynamical diradical behavior governed by structural
      fluctuation in pentacene using ab initio molecular dynamics simulation. In
      contrast to static equilibrium configuration of pentacene with a closed-shell
      ground state without diradical character, due to structural fluctuation, some of
      its dynamical snapshot configurations exhibit an open-shell broken-symmetry
      singlet ground state with diradical character, and such diradical character
      presents irregular pulsing behavior in time evolution. Not all structural changes
      can lead to diradical character, only those involving the shortening of cross
      linking C-C bonds and variations of the C-C bonds in polyacetylene chains are the
      main contributors. This scenario about diradicalization is distinctly different
      from that in long acenes. The essence is that structural distortion cooperatively
      raises the HOMO and lowers the LUMO, efficiently reducing the HOMO-LUMO and
      singlet-triplet energy gaps, which facilitate the formation of a broken-symmetry
      open-shell singlet state. The irregular pulsing behavior originates from the
      mixing of normal vibrations in pentacene. This fascinating behavior suggests the
      potential application of pentacene as a suitable building block in the design of
      new electronic devices due to its magnetism-controllability through energy
      induction. This work provides new insight into inherent electronic property
      fluctuation in acenes. 

PMID- 25946578
TI  - Consensus recommendations for the diagnosis and treatment of multiple sclerosis:
      the Middle East North Africa Committee for Treatment and Research In Multiple
      Sclerosis (MENACTRIMS).
AB  - With evolving diagnostic criteria and the advent of new oral and parenteral
      therapies for MS, most current diagnostic and treatment algorithms need re
      evaluation and updating. The diagnosis of MS relies on incorporating clinical and
      paraclinical findings to prove dissemination in space and in time, and exclude
      alternative diseases that can explain the findings at hand. The differential
      diagnostic workup should be guided by clinical and laboratory red flags to avoid
      unnecessary tests. Appropriate multiple sclerosis (MS) therapy selection is
      critical to maximize patient benefit. The current guidelines review the
      scientific evidence supporting treatment of acute relapses, radiologically
      isolated syndrome, clinically isolated syndrome, relapsing remitting MS,
      secondary progressive MS, and primary progressive MS. The purpose of these
      guidelines is to provide practical recommendations and algorithms for the
      diagnosis and treatment of MS based on current scientific evidence and clinical
      experience. 

PMID- 25946579
TI  - Biocompatible colloidal dispersions as potential formulations of natural
      pyrethrins: a structural and efficacy study.
AB  - Biocompatible colloidal dispersions of the micro- and nanoemulsion type based on
      lemon oil terpenes, polysorbates, water, and glycerol were used for the
      formulation of pyrethrins, botanical insecticides derived from the white
      pyrethrum daisy, Tanacetum cinerariifolium. The proposed formulation is based on
      pyrethrin-containing water-in-oil (W/O) microemulsions that could be diluted in
      one step with an aqueous phase to obtain kinetically stable oil-in-water (O/W)
      nanoemulsions. Structural characteristics of the micro- and nanoemulsions were
      evaluated by electron paramagnetic resonance (EPR) spectroscopy, dynamic light
      scattering (DLS), small angle X-ray scattering (SAXS), and electrical
      conductivity. Dynamic properties of the surfactant monolayer as evidenced by EPR
      measurements were affected by the water content, the surfactant, and also the
      presence of the biocide. DLS and SAXS experiments of the nanoemulsions indicated
      the existence of two populations of oil droplets dispersed in the aqueous phase,
      globular droplets of 36-37 nm in diameter, and also larger droplets with
      diameters >150 nm. All of the applied techniques for structural determination
      revealed the participation of the biocide in the nanostructure. The insecticidal
      effect of the encapsulated natural pyrethrin was evaluated in laboratory
      bioassays upon a target-insect pest, the cotton aphid Aphis gossypii Glover
      (Hemiptera: Aphididae) in eggplant, and was found to be increased compared to the
      commercial pyrethrin formulation. 

PMID- 25946580
TI  - [Perinatal health indicators: differences between the information recorded by the
      National Institute of Statistics and by the hospitals].

PMID- 25946581
TI  - [Controversial issues in economic evaluation (I): perspective and costs of Health
      Care interventions].
AB  - Economic evaluation of health care interventions has experienced a strong growth
      over the past decade and is increasingly present as a support tool in the
      decisions making process on public funding of health services and pricing in
      European countries. A necessary element using them is that agents that perform
      economic evaluations have minimum rules with agreement on methodological aspects.
      Although there are methodological issues in which there is a high degree of
      consensus, there are others in which there is no such degree of agreement being
      closest to the normative field or have experienced significant methodological
      advances in recent years. In this first article of a series of three, we will
      discuss on the perspective of analysis and assessment of costs in economic
      evaluation of health interventions using the technique Metaplan. Finally,
      research lines are proposed to overcome the identified discrepancies. 

PMID- 25946582
TI  - Spanish Interdisciplinary Committee for Cardiovascular Disease Prevention and the
      Spanish Society of Cardiology Position Statement on Dyslipidemia Management:
      differences between the European and American Guidelines.
AB  - The publication of the 2013 American College of Cardiology/American Heart
      Association guidelines on the treatment of high blood cholesterol has had a
      strong impact due to the paradigm shift in its recommendations. The Spanish
      Interdisciplinary Committee for Cardiovascular Disease Prevention and the Spanish
      Society of Cardiology reviewed this guideline and compared it with current
      European guidelines on cardiovascular prevention and dyslipidemia management. The
      most striking aspect of the American guideline is the elimination of the low
      density lipoprotein cholesterol treat-to-target strategy and the adoption of a
      risk reduction strategy in 4 major statin benefit groups. In patients with
      established cardiovascular disease, both guidelines recommend a similar
      therapeutic strategy (high-dose potent statins). However, in primary prevention,
      the application of the American guidelines would substantially increase the
      number of persons, particularly older people, receiving statin therapy. The
      elimination of the cholesterol treat-to-target strategy, so strongly rooted in
      the scientific community, could have a negative impact on clinical practice,
      create a certain amount of confusion and uncertainty among professionals, and
      decrease follow-up and patient adherence. Thus, this article reaffirms the
      recommendations of the European guidelines. Although both guidelines have
      positive aspects, doubt remains regarding the concerns outlined above. In
      addition to using risk charts based on the native population, the messages of the
      European guideline are more appropriate to the Spanish setting and avoid the
      possible risk of overtreatment with statins in primary prevention. 

PMID- 25946583
TI  - [Spatial analysis of mortality from cardiovascular diseases in Madrid City,
      Spain].
AB  - BACKGROUND: Cardiovascular disease is the leading cause of death worldwide, but
      its spatial distribution is not homogeneous. The objective of this study is to
      analyze the spatial pattern of mortality from these diseases for men and women,
      in the populated urban area (AUP) of the municipality of Madrid, and to identify
      spatial aggregations. METHODS: An ecological study was carried out by census
      tract, for men and women in 2010. Standardized Mortality Ratio (SMR), Relative
      Risk Smoothing (RRS) and Posterior Probability (PP) were calculated to consider
      the spatial pattern of the disease. To identify spatial clusters the Moran index
      (Moran I) and the Local Index of Spatial Autocorrelation (LISA) were used. The
      results were mapped. RESULTS: SMR higher than 1.1 was observed mainly in central
      areas among men and in peripheral areas among women. The PP that RRS was higher
      than 1 surpassed 0.8 in the center and in the periphery, in both men and women.
      Moran's I was 0.04 for men and 0.03 for women (p <0.05 in both cases).
      CONCLUSIONS: Sex differences were observed in the spatial distribution of
      mortality cases. RME RRS and PP maps showed a heterogeneous pattern in men,
      whereas in women a clearer pattern was detected, with a relatively higher risk in
      peripheral areas of the AUP. The LISA method showed similar patterns to those
      previously observed.

PMID- 25946584
TI  - [Change in productivity losses due to premature deaths in Spain: 2005-2009].
AB  - BACKGROUND: The economic impact caused by diseases goes far beyond health care
      costs and, therefore it is transferred to the society through different
      dimensions. The aim of this study was to estimate the productivity losses due to
      premature deaths caused by diseases occurred in Spain during the period 2005
      2009. METHODS: We used data from several sources (Death Registry, Labour Force
      Survey and Wage Structure Survey) to develop a simulation model based on the
      human-capital approach that allowed us to estimate the labour productivity losses
      caused by premature deaths in the period analysed. Additionally, we also carried
      out two alternative scenarios in which we analysed how epidemiologic data
      influenced our results. RESULTS: Our model showed the estimated loss of
      productivity due to premature death fell from 8,935 billion euros in 2005 to
      8,073 billion euros in 2009. Nine diseases (traffic accidents, malignant tumour
      of the trachea, suicides, acute myocardial infarction, AIDS, cirrhosis, breast
      tumour, cerebrovascular disease and colon cancer) accounted for 35.6% of the
      total Years of Potential Productive Life Lost and 36.5% of the estimated
      productivity losses. The estimated losses represented 0.98%, 0.85% and 0.77% of
      Gross Domestic Product in 2005, 2007 and 2009, respectively. CONCLUSIONS: The
      labour productivity losses caused by premature deaths decreased substantially in
      the period analysed. This reduction was mainly due to the epidemiological
      evolution of premature mortality.

PMID- 25946585
TI  - [Quality of life and health status in institutionalized elderly with dementian].
AB  - BACKGROUND: Studies that deepen in the aspects related to quality of life (QoL)
      of elderly with dementia living in nursing homes in Spain are needed. The aim of
      this study is to describe the QoL and related aspects in this population.
      METHODS: Sample of 525 people with dementia older than 60 years in 14 nursing
      homes. QoL was assessed with EQ-5D (both index and visual analogue Scale, EQ-VAS)
      and Quality of Life in Alzheimer's Disease(QoL-AD, resident and caregiver
      versions). Other scales were also applied: Clinical Dementia Rating Scale (CDR),
      Barthel Index, Cornell Scale for Depression in Dementia (CSDD), modified version
      of the Cumulative Illness Rating Scale for Geriatrics (CIRS-G), Short Portable
      Mental Status Questionnaire (SPMSQ) and Cognitive Mini-exam (MEC). To determine
      the relationship between the variables of interest, Pearson's correlation
      coefficient and the analysis of variance (Student's t test) were used. RESULTS:
      QoL scales displayed correlations from 0.17 to 0.50 between them. Qol-AD
      caregiver scored higher in men with lower disability and depression 28.94 +/-
      4.91, 29.91 +/- 4.74 and 28.44 +/- 4.94, respectively;(p < 0.01), and correlated
      0.45 with Barthel Index and -0.36 with CSDD. Qol-AD-resident scored higher in
      absence of depression (29.29 +/- 6.03). EQ-5D Index scored higher in men (0.19 +/
      0.33) with less disability (0.42 +/- 0.32) and its coefficient of correlation
      with Barthel Index was 0.79. CONCLUSIONS: Functional state and depression are
      associated with quality of life in older people with dementia living in nursing
      homes.

PMID- 25946586
TI  - [Health-Related Quality of Life as an Explanatory Variable of Primary Care
      Consultations: sex Differences].
AB  - BACKGROUND: It is well known the inverse relationship between health-related
      quality of life (HRQoL) and the use of consultations. However, most studies deal
      sex as a confounding variable rather than to explicitly investigate sex
      differences. The study aims to know the influence of HRQoL of the elderly on the
      use of Primary Care consultations in a sex analysis. METHODS: Throughout 2013,
      191 women and 155 men aged 65 years or older were enrolled in the study and
      assessed with interviews and analysis of medical records. We used the EuroQol-5D
      to assess the HRQoL and several demographic, clinical and social support
      variables were also analyzed. Two multiple linear regression models were
      developed. RESULTS: HRQoL showed a negative correlation with the use of
      consultations (Spearman's rho=-0,22; p=0,0001) and a crude OR value of 1,85 (95%
      CI:1,2-2,9). The association remained significant after adjusting for demographic
      [OR=1,99 (95% CI: 1,2-3,2)], clinical [OR=1,79 (95% CI: 1,1-2,9)] or social
      support covariates [OR=1,83 (95% CI: 1,1-2,9)]. In regression analysis, the
      values of standardized coefficient (beta) related to HRQoL were 0,22 (95% CI:
      36,7- -6,9) in females and 0,03 (95% CI:-15,6-23,1) in males. CONCLUSIONS: In
      women >= 65 years, HRQoL shows the greatest explanatory power of use of
      consultations, after adjusting for demographic, clinical and social support
      covariates. By contrast, its influence on men is negligible.

PMID- 25946587
TI  - [Sociodemographic Factors Related to Plasma Concentrations of 25-OH Vitamin D and
      PTH in Cord Blood].
AB  - BACKGROUND: Plasma 25(OH)D levels in the newborn are dependent on maternal
      stores, thus, neonates of vitamin D-deficient mothers present a greater risk of
      hypocalcaemia, rickets and infections the first year of life. Several studies
      showing a high prevalence of vitamin D deficiency in pregnant women have been
      published recently. The aim of the study is to analyze the levels of 25(OH)D in
      cord blood and determine whether there is a relation with nutritional,
      socioeconomic and clinical factors of pregnant women and their newborns. METHODS:
      Between March and May 2013, 99 pregnant women were recruited in Hospital del Mar
      (Barcelona), in whom plasma 25(OH)D and PTH levels were measured in cord blood at
      birth. Clinical history data were collected and a nutritional survey was made on
      maternal vitamin D and calcium intake and sun exposure. Statistical analysis was
      performed using SPSS. Comparisons were performed using Kruskal-Wallis and Mann
      Whitney U tests, and correction for multiple comparisons using Bonferroni. P
      value <0.05 and <0.0083 for multiple comparisons were considered statistically
      significant. RESULTS: Mean 25(OH)D value in cord blood was 10.4 +/- 6 .1 ng/ml.
      94% of pregnant women had 25(OH)D levels in cord blood <20 ng/ml. Vitamin D and
      calcium intake was considered adequate in 92% although sun exposure was deficient
      in 47%. A correlation between serum 25(OH)D and vitamin D (p 0.033) and calcium
      intake (p 0.005), sun exposure (p<0.001), ethnicity (p<0.001), skin phototype
      (p<0.001) and use of traditional clothing (p<0.001) was found. CONCLUSIONS: There
      is a high prevalence of low levels of vitamin D after winter months in cord
      blood. The lowest 25(OH D levels were observed in Indo-Pakistani ethnicity, dark
      phototype and deficient sun exposure.

PMID- 25946588
TI  - [Quality of the Spanish Vital Statistics to Estimate Perinatal Health Outcomes:
      small and Large for Gestational Age].
AB  - BACKGROUND: Relative measures of birthweight (small and large-for-gestational
      age, SGA-LGA) are increasingly preferred to absolute measures (low birthweight,
      macrosomia). In this study we assess whether the national vital statistics
      provided by the Spanish National Statistical Institute (INE) reliably estimate
      SGA and LGA. Also, we will assess whether missing data (selection) and
      misreported information (bias) are systematically associated with parental
      socioeconomic information. METHODS: We linked the information on 6,339 births at
      the Hospital Clinico San Carlos of Madrid (2005-06) with the vital statistics
      records (successful for the 95% of the observation). Validity measures and
      concordance were estimated for low birthweight (LBW, <2500 gr), macrosomia (>4500
      gr), SGA (<10th percentile) and LGA (>90 percentile). Logistic regressions were
      fitted. RESULTS: The prevalence estimated with the hospital data were: LBW (6%),
      macrosomia (0.5%) SGA (1%) and LGA (15%) and, with the data from INE: 5% 0.5% 2%
      12% respectively. Kappa statistics: LBW (83%), macrosomia (79%), PEG (24%) and
      LGA (82%). Missing and misreported data vary with parental nationality and their
      situation in the labor market (OR between 1.5 y 2.2). CONCLUSIONS: Vital
      statistics overestimate the prevalence of SGA and underestimate the prevalence of
      LGA. The concordance between the sources is very good for low birthweight,
      macrosomia and LGA, and moderately good for SGA. Both missing and misreported
      birthweight and gestational age are associated with parental socioeconomic
      characteristics.

PMID- 25946589
TI  - [Cost of breast cancer treatment by clinical stage in the Basque Country, Spain].
AB  - BACKGROUND: The burden of breast cancer is important for the healthcare system.
      In the context of the evaluation of the breast cancer screening program in the
      Basque Country it is important to determine the unitary costs related to
      diagnosis as well as the treatment costs depending on the clinical stage at
      detection. The main objective was to calculate the total cost and the components
      of breast cancer (BC) treatment depending on the clinical stage by 2011. METHODS:
      The estimated costs include BC diagnosis as so as to initial treatment and follow
      up, based on resource consumption and unitary costs of the Basque Health
      Services. Micro-costing technique was applied based on the clinical guidelines.
      RESULTS: Our model showed the estimated loss of productivity due to premature The
      initial cost was 9.838? for the stage 0, 17.273? for stage I, 22.145? for stage
      II and 28.776? for stage III. The follow up annual cost was 172? for the stage 0,
      908? for stage I, 994? for stage II and 1.166? for stage III. The annual cost for
      stage IV was 17879?. CONCLUSIONS: Chemotherapy determines the greatest percentage
      of BC costs. The two main drivers of the total cost of breast cancer are the
      initial treatment of stages I to III and the cost of stage IV, the latter
      reaching ? 50,061 per patient.

PMID- 25946590
TI  - [Outbreak due to butterfish consumption: keriorrhea and histamine poisoning].
AB  - BACKGROUND: The consumption of butterfish is spreading in our country; if
      appropriate standards of conservation and preparation of this type of food are
      not met may cause poisoning. The objective is to describe an outbreak of
      histamine poisoning and double cerous esters after consumption butterfish.
      METHODS: A descriptive study of the double intoxication at a banquet held in July
      2013 in Valladolid. It was studied by filling a specific survey, by phone or by
      the medical centers who treated the guests. The database and subsequent
      descriptive statistical analyzes were performed with Microsoft Excel Professional
      Plus 2010 program. RESULTS: Of the 27 cases reported in 24 we obtained
      information on symptoms. The attack rate was 22.5 %, with a clinical picture in
      which predominant diarrhea (75%), headache (46%), abdominal pain (38%) and
      sweating (38%), highlighting its specificity itching/burning of mouth (29%). Four
      patients had orange and oily stools (keriorrhea). The average time from the start
      of dinner to onset of symptoms was 119 minutes. The mean duration of symptoms was
      14 hours. Analytical served fish showed histamine levels above 2,000 mg / kg.
      CONCLUSIONS: A double poisoning (histamine and cerous esters) was produced by
      consumption of butterfish. The picture was mild and self-limiting. You need to
      know this type of poison to properly handle avoiding unnecessary tests, and to
      notify the health authority for investigation and subsequent adoption of
      appropriate measures.

PMID- 25946591
TI  - [Characteristics of the Videos in Spanish Posted on Youtube about Human
      Papillomavirus Vaccines].
AB  - BACKGROUND: Internet is a resource to search for health-related information. The
      aim of this work was to know the content of the videos in Spanish language of
      YouTube related to the vaccine against the human papilloma virus (HPV). METHODS:
      An observational study was conducted from a search on YouTube on 26th July 2013
      by using keywords such as: "human papilloma virus vaccine", "HPV vaccine",
      "Gardasil vaccine", "Cervarix vaccine". Different categories were established
      according to: the type of vaccine, the published source and the favorable or
      unfavorable predisposition towards the human papillomavirus vaccination. The
      number of visits and the duration of the videos were gathered, with analysis of
      variables in the 20 most visited videos. RESULTS: A total of 170 videos were
      classified like: local news (n=39; 37 favorable, 2 unfavorable; 2:06:29; 42972
      visits), national news (n=32; 30/2; 1:49:27; 50138 visits), created by YouTube
      subscribers (n=21; 21/1; 1:44:39; 10991 visits), advertisements (n=21; 19/2;
      0:27:05; 28435 visits), conferences (n=17; 15/2; 3:25:39; 27206 visits),
      documentaries (n=16; 12/4; 2:11:31; 30629 visits). From all of the 20 most viewed
      YouTube videos predominated those which were favorable to the vaccination (n=12;
      0:43:43; 161789 visits) against the unfavorable (n=8; 2:44:14; 86583 visits).
      CONCLUSIONS: Most of the videos have a favorable opinion towards HPV vaccine,
      although videos with a negative content were the longest and most viewed.

PMID- 25946592
TI  - [Delay surgical treatment of hip fracture: continuing problems].

PMID- 25946593
TI  - Management of non-invasive rhinosinusitis in the immunosuppressed patient
      population.
AB  - OBJECTIVE: Rhinologists are seeing an increasing number of immunosuppressed
      patients. Currently, no treatment paradigm exists for treating acute and chronic
      noninvasive rhinosinusitis (ARS, CRS) in this growing population. This study aims
      to identify patient and treatment factors that affect rhinosinusitis outcomes in
      this vulnerable population. STUDY DESIGN: Prognostic retrospective cohort study.
      METHODS: Immunocompromised patients treated by rhinologists for ARS or CRS
      10/2007 to 10/2012 were identified by rhinosinusitis diagnostic codes, codes for
      transplant, cancer, HIV, diabetes, and codes indicating immunosuppression in the
      intensive care setting. Associations between patient factors and outcome were
      analyzed by logistic regression. Associations between treatment and outcome were
      analyzed by Firth logistic regression. RESULTS: A total of 132 subjects were
      identified. Of those, 90.9% had CRS and 9.1% had ARS; 12.9% were transplant
      patients; 47% were diabetic; 37.9% were cancer patients; and 16.7% were in the
      intensive care unit. Patients with higher American Society of Anesthesiologists
      (ASA) scores had decreased disease resolution (odds ratio [OR] = 0.5, P = 0.021).
      Transplant patients (OR = 22.5, P = 0.001), diabetics patients (OR = 6.4, P =
      0.017), cancer patients (OR = 5.4, P = 0.046), and patients with prior medical
      therapy for rhinosinusitis (OR = 5.84, P < 0.001) had increased disease
      resolution compared to immunosuppressed critical care patients. Patients treated
      with antibiotics alone had no statistically significant difference in disease
      resolution compared to those receiving no treatment. In contrast, treatment plans
      including surgery were associated with greater disease resolution. CONCLUSION:
      This data indicates that surgical treatment provides improved outcomes for
      patients presenting with acute exacerbations of rhinosinusitis related to their
      immunocompromised state. Given the limited study population, these findings may
      not apply to HIV-positive or ARS patients, and further study should be undertaken
      in these groups. LEVEL OF EVIDENCE: 4.

PMID- 25946594
TI  - Mercury deposition and re-emission pathways in boreal forest soils investigated
      with Hg isotope signatures.
AB  - Soils comprise the largest terrestrial mercury (Hg) pool in exchange with the
      atmosphere. To predict how anthropogenic emissions affect global Hg cycling and
      eventually human Hg exposure, it is crucial to understand Hg deposition and re
      emission of legacy Hg from soils. However, assessing Hg deposition and re
      emission pathways remains difficult because of an insufficient understanding of
      the governing processes. We measured Hg stable isotope signatures of radiocarbon
      dated boreal forest soils and modeled atmospheric Hg deposition and re-emission
      pathways and fluxes using a combined source and process tracing approach. Our
      results suggest that Hg in the soils was dominantly derived from deposition of
      litter (~90% on average). The remaining fraction was attributed to precipitation
      derived Hg, which showed increasing contributions in older, deeper soil horizons
      (up to 27%) indicative of an accumulation over decades. We provide evidence for
      significant Hg re-emission from organic soil horizons most likely caused by
      nonphotochemical abiotic reduction by natural organic matter, a process
      previously not observed unambiguously in nature. Our data suggest that Histosols
      (peat soils), which exhibit at least seasonally water-saturated conditions, have
      re-emitted up to one-third of previously deposited Hg back to the atmosphere. Re
      emission of legacy Hg following reduction by natural organic matter may therefore
      be an important pathway to be considered in global models, further supporting the
      need for a process-based assessment of land/atmosphere Hg exchange.

PMID- 25946595
TI  - Mid-term radiological and functional results of biological reconstructions of
      extremity-located bone sarcomas in children and young adults.
AB  - Biological reconstruction is a useful option for reconstruction following bone
      sarcoma resection in children. The mid-term functional and radiological outcomes
      of biological reconstructions after resection of bone sarcomas in children are
      presented in this study. Eighteen patients [average age 12.5 years (range 4-22
      years)] with primary sarcomas of long bones underwent wide surgical resection and
      biological reconstruction. The bone defects were managed by intercalary (n=14),
      osteoarticular (n=3) reconstructions and arthrodesis (n=1) with a vascularized
      fibular graft (VFG). VFG was combined with a massive allograft in seven lower
      extremity reconstructions. The average follow-up was 45.7 months (range 25-78
      months). Graft union and graft hypertrophy was observed in 17 (94.4%) of 18
      patients at 12 months. The VFG-allograft osteointegration rate was 100% at 24
      months. The average final follow-up Musculoskeletal Tumor Society (MSTS) scores
      for lower and upper extremity reconstructions were 79.7% (range 66.6-90%) and
      80.9% (range 53.3-100%), respectively. Four (22.2%) complications, including
      nonunion (n=1), implant failure (n=1), infection (n=1) and skin necrosis (n=1),
      required reoperation. The disease relapsed in three (16.6%) patients. Defect size
      and VFG length did not correlate with MSTS scores and radiological parameters
      (P>0.05). Biological reconstruction with VFG can provide permanent stability and
      progressively increasing functional and radiological results. 

PMID- 25946596
TI  - The renaissance of developmental biology.
AB  - Since its heyday in the 1980s and 90s, the field of developmental biology has
      gone into decline; in part because it has been eclipsed by the rise of genomics
      and stem cell biology, and in part because it has seemed less pertinent in an era
      with so much focus on translational impact. In this essay, I argue that recent
      progress in genome-wide analyses and stem cell research, coupled with
      technological advances in imaging and genome editing, have created the conditions
      for the renaissance of a new wave of developmental biology with greater
      translational relevance. 

PMID- 25946597
TI  - Comparison of readout segmented echo planar imaging (EPI) and EPI with reduced
      field-of-VIew diffusion-weighted imaging at 3t in patients with breast cancer.
AB  - PURPOSE: To qualitatively and quantitatively compare the diagnostic performance
      of rs-EPI (readout segmented echo planar imaging) and reduced FOV (field-of-view)
      EPI in patients with biopsy-proven breast cancer at 3T. MATERIALS AND METHODS:
      Between November 2013 and July 2014, 96 patients (age range, 30-75 years: mean,
      52 years) with breast cancer were retrospectively enrolled in this study. In all
      patients, rs-EPI and rFOV EPI were performed using a 3T MR scanner. Differences
      between two sequences were compared quantitatively by measuring the tumor
      apparent diffusion coefficient (ADC), signal-to-noise ratio (SNR), contrast, and
      contrast-to-noise ratio (CNR). Two independent readers visually assessed overall
      image quality, lesion conspicuity, and reader preference. The regions of interest
      (ROIs) were drawn in the whole tumor and in the normal breast parenchyma.
      Comparisons of quantitative and qualitative parameters between two sequences were
      performed using the Mann-Whitney and the paired t-test. RESULTS: SNR was
      significantly higher in rFOV EPI than in rs-EPI (51.88 +/- 27.68 vs. 76.46 +/-
      50.20, P < 0.001). Mean tumor ADC value and normal tissue ADC were significantly
      lower in rFOV EPI (P < 0.001). Absolute tumor mean and minimum ADCs of rFOV EPI
      were significantly lower than those of rs-EPI (P < 0.001 for both). However,
      normalized ADC did not show a significant difference between the two sequences (P
      = 0.737). Lesion conspicuity and overall image quality of rFOV EPI were
      significantly higher than those of rs-EPI for both readers (P = 0.025 and <
      0.001). CONCLUSION: In breast cancer, rFOV EPI provided significantly higher
      image quality, lesion conspicuity, and SNR than rs-EPI.

PMID- 25946598
TI  - Dexamethasone prevents hearing loss by restoring glucocorticoid receptor
      expression in the guinea pig cochlea.
AB  - OBJECTIVES/HYPOTHESIS: Dexamethasone is widely used in the treatment of various
      inner ear diseases. However, knowledge about its direct impact on glucocorticoid
      receptor (GR) expression is still limited. STUDY DESIGN: Prospective animal study
      in male guinea pigs. METHODS: A therapeutic concentration of dexamethasone (8
      mg/mL) or a physiological concentration of NaCl (0.9% solution) were
      intratympanically injected into the ears of guinea pigs (n = 10 in each case) 14
      hours prior to 90 dB noise exposure (1 hour). Eighteen ears were exposed to noise
      only. Seven untreated ears were used as controls. Auditory brainstem responses
      were recorded prior to noise exposure or treatment and 2 hours thereafter. The
      cochleae were removed from the bullae, transferred to fixative, and embedded in
      paraffin. GR expression was identified immunohistochemically in the cochlea.
      Local staining intensities were quantified for seven regions by a computer.
      RESULTS: Dexamethasone application significantly lowered noise-induced hearing
      loss. Statistically significant alterations in the average GR expression levels
      were identified exclusively in the spiral ligament. Comparing GR expression at
      the level of individual ear, numerous highly significant local associations were
      identified in the other six cochlear regions. CONCLUSIONS: The intratympanic
      application of dexamethasone is suitable for supporting cochlear homeostasis
      under stress conditions. The lateral wall, mainly responsible for potassium
      recycling, seems to be the main target in glucocorticoid therapy.

PMID- 25946599
TI  - Vibronic Structures in Absorption and Fluorescence Spectra of Firefly
      Oxyluciferin in Aqueous Solutions.
AB  - To elucidate the factors determining the spectral shapes and widths of the
      absorption and fluorescence spectra for keto and enol oxyluciferin and their
      conjugate bases in aqueous solutions, the intensities of vibronic transitions
      between their ground and first electronic excited states were calculated for the
      first time via estimation of the vibrational Franck-Condon factors. The major
      normal modes, overtones and combination tones in absorption and fluorescence
      spectra are similar for all species. The theoretical full widths at half maximum
      of absorption spectra are 0.4-0.7 eV and those for the fluorescence spectra are
      0.4-0.5 eV, except for phenolate-keto that exhibits exceptionally sharp peak
      widths due to the dominance of the 0-0' or 0'-0 band. These spectral shapes and
      widths explain many relevant features of the experimentally observed spectra. 

PMID- 25946601
TI  - Lower Extremity Osseous Oncologic Reconstruction with Composite Microsurgical
      Free Fibula Inside Massive Bony Allograft.
AB  - BACKGROUND: Lower extremity reconstruction after resection of long bone tumors in
      children is challenging because of the unique functional demands and growth
      potential of the lower extremity. The use of a free fibula flap inside a massive
      bone allograft provides a reliable reconstructive option. The authors evaluate
      the surgical and functional outcomes of using this technique. METHODS: This is a
      retrospective review of 12 consecutive patients who underwent reconstruction of
      segmental femur or tibia defects using a free fibula flap inside a massive bone
      allograft between 2003 and 2011. Complications and functional outcomes are
      reported. RESULTS: Twelve patients with a mean age of 15.8 years (range, 3 to 49
      years) were included in the study. Eight femur defects and four tibia defects
      were reconstructed. The mean follow-up time was 41.4 months. Two constructs were
      removed because of infection, three patients required bone grafting for nonunion,
      one patient required an additional operation to excise a skin paddle, and one
      patient experienced a lower extremity deep vein thrombosis. The mean time to
      achieve full weight bearing was 14.3 months. CONCLUSIONS: The use of a free
      fibula flap inside a massive bone allograft after bone tumor resection provides
      an option for lower extremity reconstruction. The allograft component increases
      the initial strength of the reconstruction, whereas the vascularized fibula
      component is thought to increase the biologic potential for osteosynthesis and
      ultimately provide a potentially lifelong durable reconstruction. Patients who
      achieve oncologic control are likely to enjoy a highly functional long-term
      outcome. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 25946602
TI  - Autologous Adipose Stromal Cells Seeded onto a Human Collagen Matrix for Dermal
      Regeneration in Chronic Wounds: Clinical Proof of Concept.
AB  - BACKGROUND: Nonhealing wounds are unable to integrate skin autografts by
      avascular and fibrotic dermal tissue. Adipose-derived stromal cells can improve
      the local environment of the wound bed by angiogenesis and immunomodulation. This
      work aimed to develop a biological dressing made of adipose-derived stromal cells
      onto a human acellular collagen matrix. METHODS: Adipose-derived stromal cells
      were isolated from human adipose tissue (n = 8). In vitro, the genetic stability
      during early and late passages (1, 4, 10, and 16) and vascular endothelial growth
      factor (VEGF) secretion were assessed. Adipose-derived stromal cell adhesion and
      spreading on collagen matrix were preliminarily studied. In vivo tumorigenicity,
      angiogenesis, and tissue oxygenation were assessed after implantation of the
      construct in nude rats (n = 10). The biological dressing was manufactured and
      implanted in three patients with chronic wounds. RESULTS: In vitro, aneuploidies,
      but no clonal transformation, were detected up to late cellular passages. VEGF
      was secreted more during hypoxia (0.1% oxygen) than during normoxia (21% oxygen).
      Adipose-derived stromal cells can adhere and spread on the scaffold within 18 to
      20 days. No tumor development occurred 3 months after implantation in
      immunocompromised rats. Vessel counts and tissue oxygenation were higher after
      adipose-derived stromal cell implantation. In patients, granulation tissue was
      found (276 percent of vessel density), followed by epithelialization or split
      thickness skin engraftment up to 22 months after implantation. CONCLUSIONS:
      Implantation of adipose-derived stromal cells seeded onto human acellular
      collagen matrix (biological dressing) represents a promising therapy for
      nonhealing wounds, offering improvement in dermal angiogenesis and remodeling.
      This therapy using autologous stromal cells is safe, without significant genetic
      alterations after in vitro expansion.

PMID- 25946603
TI  - An Evidence-Based Model for the Successful Treatment of Flank and Lateral
      Abdominal Wall Hernias.
AB  - BACKGROUND: Lateral abdominal wall defects are a significant contributor to
      patient morbidity and mortality in the United States. Reconstruction involving
      flank hernias and bulges is relatively scarce in the literature despite its
      serious consequences. The authors aim to identify an objective approach for the
      evaluation and successful repair of defects of the lateral abdominal wall.
      METHODS: A retrospective analysis was carried out on patients presenting for open
      repair of a lateral wall defect performed by a single surgeon. Over a 5-year
      period, there were 29 consecutive patients with a mean follow-up period of 21.2
      months. Patient demographics including body mass index, number of hernia defects,
      number of previous repairs/abdominal operations, defect size, operative time,
      blood loss, and complications (e.g., recurrence/bulge, seroma, hematoma, wound
      infection, persistent pain, skin breakdown, and fascial dehiscence) were
      collected. RESULTS: Patients who underwent flank hernia repairs using an
      inlay/underlay nonbridged technique with the use of acellular dermal matrix had
      low recurrence and overall complication rates. Only one patient (3.4 percent) had
      a recurrence at follow-up, and another patient (3.4 percent) had developed a
      bulge. CONCLUSIONS: The authors' data indicate successful results when their
      technique is applied. Proper patient selection is essential, along with a
      thorough understanding of anatomy and techniques for successful reconstruction.
      The authors recommend using an inlay (preferred) or underlay repair with
      acellular dermal matrix to reinforce the surrounding musculofascial closure. This
      technique, in conjunction with the authors' holistic abdominal wall
      reconstruction protocol, has optimized outcomes and identified a successful
      multidisciplinary strategy for the reconstruction of lateral wall defects.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 25946604
TI  - Latissimus Dorsi Flap for Total Autologous Immediate Breast Reconstruction
      without Implants.

PMID- 25946605
TI  - Tuberous Breast Deformity: Classification and Treatment Strategy for Improving
      Consistency in Aesthetic Correction.

PMID- 25946606
TI  - Flap Failure in 2013: A Perfect Year for American College of Surgeons National
      Surgical Quality Improvement Program Microsurgeons?

PMID- 25946607
TI  - An Effective and Novel Technique for Hair Control in Craniofacial Surgery.

PMID- 25946609
TI  - Reply: Suction Drain-Assisted Split-Thickness Skin Grafting: A Simple Procedure
      to Improve Skin Graft Take.

PMID- 25946610
TI  - European and American Microsurgery Training Programs: The Fellowship Concept
      Difference.

PMID- 25946608
TI  - Alternatively Activated M2 Macrophages Improve Autologous Fat Graft Survival in a
      Mouse Model through Induction of Angiogenesis.

PMID- 25946611
TI  - Using Callus Cushions as a Simple Approach for Postoperative Dressing after
      Nipple Reconstruction.

PMID- 25946612
TI  - Swings and Roundabouts: Paradoxes of the Away Rotation.

PMID- 25946613
TI  - Surgical Justice.

PMID- 25946614
TI  - Total Syntheses of (-)-Mersicarpine, (-)-Scholarisine G, (+)-Melodinine E, (-)
      Leuconoxine, (-)-Leuconolam, (-)-Leuconodine A, (+)-Leuconodine F, and (-)
      Leuconodine C: Self-Induced Diastereomeric Anisochronism (SIDA) Phenomenon for
      Scholarisine G and Leuconodines A and C.
AB  - Enantioselective total syntheses of title natural products from a common
      cyclohexenone derivative (S)-18 were reported. Ozonolysis of (S)-18 afforded a
      stable diketo ester (R)-17 that was subsequently converted to two skeletally
      different natural products, i.e., (-)-mersicarpine (8) with a [6.5.6.7] fused
      tetracyclic ring system and (-)-scholarisine G (9) with a [6.5.6.6.5] fused
      pentacyclic skeleton, respectively. The postcyclization diversification was
      realized by taking advantage of the facile conversion of (+)-melodinine E (6) to
      N-acyliminium ion 7, from which a hydroxy group was selectively introduced to the
      C6, C7, C10 and the central C21 position of diazafenestrane system, leading to (
      )-leuconodine A (11), (+)-leuconodine F (12), (-)-scholarisine G (9), (-)
      leuconodine C (13), and skeletally different (-)-leuconolam (5). Furthermore, an
      unprecedented non-natural oxabridged oxadiazafenestrane 68 was formed by
      oxidation of (+)-melodinine E (6). During the course of this study, a strong self
      induced diastereomeric anisochronism (SIDA) phenomenon was observed for
      scholarisine G (9), leuconodines A (11) and C (13). X-ray structures of both the
      racemic and the enantiopure natural products 9, 11, and 13 were obtained. The
      different crystal packing of these two forms nicely explained the chemical shift
      differences observed in the (1)H NMR spectra of the racemic and the enantio
      enriched compounds in an achiral environment. 

PMID- 25946615
TI  - Role of Cytoskeletal Tension in the Induction of Cardiomyogenic Differentiation
      in Micropatterned Human Mesenchymal Stem Cell.
AB  - The role of biophysical induction methods such as cell micropatterning in stem
      cell differentiation has been well documented previously. However, the underlying
      mechanistic linkage of the engineered cell shape to directed lineage commitment
      remains poorly understood. Here, it is reported that micropatterning plays an
      important role in regulating the optimal cytoskeletal tension development in
      human mesenchymal stem cell (hMSC) via cell mechanotransduction pathways to
      induce cardiomyogenic differentiation. Cells are grown on fibronectin strip
      patterns to control cell polarization and morphology. These patterned cells
      eventually show directed commitment toward the myocardial lineage. The cell's
      mechanical properties (cell stiffness and cell traction forces) are observed to
      be very different for cells that have committed to the myocardial lineage when
      compared with that of control. These committed cells have mechanical properties
      that are significantly lower indicating a correlation between the micropatterning
      induced differentiation and actomyosin-generated cytoskeletal tension within
      patterned cells. To study this correlation, patterned cells are treated with RhoA
      pathway inhibitor. Severely down-regulated cardiomyogenic marker expression is
      observed in those treated patterned cells, thus emphasizing the direct dependence
      of hMSCs differentiation fate on the cytoskeletal tension. 

PMID- 25946616
TI  - Noninvasive measurements of glycogen in perfused mouse livers using chemical
      exchange saturation transfer NMR and comparison to (13)C NMR spectroscopy.
AB  - Liver glycogen represents an important physiological form of energy storage. It
      plays a key role in the regulation of blood glucose concentrations, and
      dysregulations in hepatic glycogen metabolism are linked to many diseases
      including diabetes and insulin resistance. In this work, we develop, optimize,
      and validate a noninvasive protocol to measure glycogen levels in isolated
      perfused mouse livers using chemical exchange saturation transfer (CEST) NMR
      spectroscopy. Model glycogen solutions were used to determine optimal saturation
      pulse parameters which were then applied to intact perfused mouse livers of
      varying glycogen content. Glycogen measurements from serially acquired CEST Z
      spectra of livers were compared with measurements from interleaved natural
      abundance (13)C NMR spectra. Experimental data revealed that CEST-based glycogen
      measurements were highly correlated with (13)C NMR glycogen spectra. Monte Carlo
      simulations were then used to investigate the inherent (i.e., signal-to-noise
      based) errors in the quantification of glycogen with each technique. This
      revealed that CEST was intrinsically more precise than (13)C NMR, although in
      practice may be prone to other errors induced by variations in experimental
      conditions. We also observed that the CEST signal from glycogen in liver was
      significantly less than that observed from identical amounts in solution. Our
      results demonstrate that CEST provides an accurate, precise, and readily
      accessible method to noninvasively measure liver glycogen levels and their
      changes. Furthermore, this technique can be used to map glycogen distributions
      via conventional proton magnetic resonance imaging, a capability universally
      available on clinical and preclinical magnetic resonance imaging (MRI) scanners
      vs (13)C detection, which is limited to a small fraction of clinical-scale MRI
      scanners. 

PMID- 25946617
TI  - Highly ordered self-assembling polymer/clay nanocomposite barrier film.
AB  - Efforts to mimic complex-structured biologically based materials such as abalone
      shell have occupied substantial research time and effort in science and
      engineering. The majority of the efforts involve tedious and expensive techniques
      and processes. Layer-by-layer (LBL) is one such technique that can produce
      materials with quite unique physical properties, approaching, and in some cases
      surpassing, those seen in nature. The LBL technique, however, is quite tedious
      and difficult to implement commercially. We report here the discovery of an
      organic/inorganic spontaneous self-assembling system that forms a highly
      structured nanocomposite. The driving force behind this self-assembly appears to
      be entropy. This discovery should open up completely new avenues to designing
      hierarchical composites and structures. The films have been studied by X-ray
      diffraction and the barrier properties for oxygen diffusion measured. 

PMID- 25946621
TI  - Evolving paradigms in the nutritional support of critically ill surgical
      patients.

PMID- 25946618
TI  - Clinical and genomic heterogeneity of Diamond Blackfan anemia in the Russian
      Federation.
AB  - BACKGROUND: Diamond Blackfan anemia (DBA) is a genetically and clinically
      heterogeneous ribosomopathy and inherited bone marrow failure syndrome
      characterized by anemia, reticulocytopenia, and decreased erythroid precursors in
      the bone marrow with an increased risk of malignancy and, in approximately 50%,
      physical abnormalities. METHODS: We retrospectively analyzed clinical data from
      77 patients with DBA born in the Russian Federation from 1993 to 2014. In 74
      families there was one clinically affected individual; in only three instances a
      multiplex family was identified. Genomic DNA from 57 DBA patients and their first
      degree relatives was sequenced for mutations in RPS19, RPS10, RPS24, RPS26, RPS7,
      RPS17, RPL5, RPL11, RPL35a, and GATA1. RESULTS: Severe anemia presented before 8
      months of age in all 77 patients; before 2 months in 61 (78.2%); before 4 months
      in 71 (92.2%). Corticosteroid therapy was initiated after 1 year of age in the
      majority of patients. Most responded initially to steroids, while 5 responses
      were transient. Mutations in RP genes were detected in 35 of 57 patients studied:
      15 in RPS19, 6 in RPL5, 3 in RPS7, 3 each in RPS10, RPS26, and RPL11 and 1 each
      in RPS24 and RPL35a; 24 of these mutations have not been previously reported. One
      patient had a balanced chromosomal translocation involving RPS19. No mutations in
      GATA1 were found. CONCLUSION: In our cohort from an ethnically diverse population
      the distribution of mutations among RP genes was approximately the same as was
      reported by others, although within genotypes most of the mutations had not been
      previously reported.

PMID- 25946622
TI  - Gamma radiation shielding and health physics characteristics of diaspore-flyash
      concretes.
AB  - Different gamma radiation interaction parameters has been measured experimentally
      for the prepared diaspore-flyash concretes at 59.54, 662, 1173 and 1332 keV using
      narrow-beam transmission geometry and results are found to be in good agreement
      with theoretical values computed with a computer programme, WinXCom. The
      radiation exposure rate and absorbed dose rate for the gamma radiation with and
      without shielding of diaspore-flyash concretes have been determined using linear
      attenuation results. The results show that on average, there is reduction of 95%,
      53% and 40% in dose rate for gamma sources (241)Am, (137)Cs and (60)Co,
      respectively with diaspore-flyash concretes as shielding material. Other health
      physics parameters namely equivalent dose, effective dose, gamma flux and energy
      fluence rate have also been determined. 

PMID- 25946623
TI  - Dramatic Enhancement of Power Conversion Efficiency in Polymer Solar Cells by
      Conjugating Very Low Ratio of Triplet Iridium Complexes to PTB7.
AB  - Various low ratios of triplet iridium complexes (0, 0.5, 1, 1.5, 2.5, and 5 mol%)
      are conjugated to the backbone of the famous champion donor polymer PTB7. At the
      same conditions, the power conversion efficiency for polymer containing 1% of Ir
      increases by 45%, 39%, and 31% in three batches of devices compared with control
      Ir-free PTB7. 

PMID- 25946625
TI  - Discussing Fractional Carbon Dioxide Laser and Other Physical Treatments for Scar
      Prevention With Patients.

PMID- 25946624
TI  - Hyperglycemic tumor microenvironment induces perineural invasion in pancreatic
      cancer.
AB  - Glucose intolerance and frank diabetes mellitus (DM) can increase the risk of
      cancer death for pancreatic cancer (PanCa). However, the mechanism by which these
      factors influence cancer deaths is not clear. In this study, we established a
      model system to mimic the pancreatic tumor microenvironment in patients with DM
      to examine the biological behavior of PanCa cells and nerves in cell culture and
      in animals. Our in vitro studies demonstrated that hyperglycemia promoted the
      proliferation and invasion of PanCa cell lines and upregulated the expression of
      nerve growth factor in these cells. Also, the migration of Schwann cells (SCs)
      was inhibited by hyperglycemia and neurites exerted pathological regeneration.
      Furthermore, the interaction between the PanCa cells and nerves was enhanced in
      the tumor microenvironment. We further showed that hyperglycemia promoted the
      perineural invasion (PNI) of PanCa in vivo. These data suggest that DM worsens
      the prognosis of PanCa because of aggravated PNI. Thus, our study illustrates a
      novel mechanism by which hyperglycemia decreases survival in patients with PanCa.

PMID- 25946627
TI  - Bore-Sight Calibration of Multiple Laser Range Finders for Kinematic 3D Laser
      Scanning Systems.
AB  - The Simultaneous Localization and Mapping (SLAM) technique has been used for
      autonomous navigation of mobile systems; now, its applications have been extended
      to 3D data acquisition of indoor environments. In order to reconstruct 3D scenes
      of indoor space, the kinematic 3D laser scanning system, developed herein,
      carries three laser range finders (LRFs): one is mounted horizontally for system
      position correction and the other two are mounted vertically to collect 3D point
      cloud data of the surrounding environment along the system's trajectory. However,
      the kinematic laser scanning results can be impaired by errors resulting from
      sensor misalignment. In the present study, the bore-sight calibration of multiple
      LRF sensors was performed using a specially designed double-deck calibration
      facility, which is composed of two half-circle-shaped aluminum frames. Moreover,
      in order to automatically achieve point-to-point correspondences between a scan
      point and the target center, a V-shaped target was designed as well. The bore
      sight calibration parameters were estimated by a constrained least squares
      method, which iteratively minimizes the weighted sum of squares of residuals
      while constraining some highly-correlated parameters. The calibration performance
      was analyzed by means of a correlation matrix. After calibration, the visual
      inspection of mapped data and residual calculation confirmed the effectiveness of
      the proposed calibration approach. 

PMID- 25946626
TI  - Ethanol Extract of Peanut Sprout Lowers Blood Triglyceride Levels, Possibly
      Through a Pathway Involving SREBP-1c in Rats Fed a High-Fat Diet.
AB  - The hypothesis of this study was that peanut sprout extracts (PSE) could reduce
      fat accumulation through activating the transcription of SREBP-1c genes. Sprague
      Dawley (SD) were randomly assigned into two groups and fed the following diet for
      4 weeks; 10 normal fat (NF, 7 g of fat/100 g diet) and 30 high fat (HF, 20 g of
      fat/100 g diet). After 4 weeks, the HF group was divided into three groups; HF,
      HF with 15 mg of PSE/kg diet (HF+low PSE, 0.025% resveratrol), and HF with 30 mg
      of PSE/kg diet (HF+high PSE, 0.05% resveratrol) and fed for an additional 5
      weeks. The HF+high PSE group had significantly lower weight gain than the HF
      group. Plasma triglyceride (TG) level and the hepatic total lipid level were
      significantly lower in the HF+high PSE group compared to the HF group. Fecal
      excretions of total lipids, cholesterol, and TG in the HF+high PSE group tended
      to be higher than in the HF group, but these differences were not significant.
      The mRNA expressions of fatty acid synthase, glucose-6-phosphate dehydrogenase,
      and sterol regulatory element binding protein-c (SREBP-1c) were significantly
      lower in the HF+high PSE group than in the HF group. The mRNA expressions of
      hydroxy-3-methylglutaryl coenzyme A reductase and acyl-CoA cholesterol
      acyltransferase were significantly lower in the HF+high PSE groups compared to
      the HF group. The mRNA expression of cholesterol 7alpha-hydroxylase1 was
      significantly higher than the HF group in both the HF+low PSE and HF+high PSE
      groups, with much greater increase observed in the HF+high PSE group. In
      conclusion, consumption of PSE was effective for improving blood lipid levels,
      possibly by suppressing the expression of SREBP-1c, in rats fed a high-fat diet. 

PMID- 25946628
TI  - Unified camera tamper detection based on edge and object information.
AB  - In this paper, a novel camera tamper detection algorithm is proposed to detect
      three types of tamper attacks: covered, moved and defocused. The edge
      disappearance rate is defined in order to measure the amount of edge pixels that
      disappear in the current frame from the background frame while excluding edges in
      the foreground. Tamper attacks are detected if the difference between the edge
      disappearance rate and its temporal average is larger than an adaptive threshold
      reflecting the environmental conditions of the cameras. The performance of the
      proposed algorithm is evaluated for short video sequences with three types of
      tamper attacks and for 24-h video sequences without tamper attacks; the algorithm
      is shown to achieve acceptable levels of detection and false alarm rates for all
      types of tamper attacks in real environments. 

PMID- 25946629
TI  - Novel real-time diagnosis of the freezing process using an ultrasonic transducer.
AB  - The freezing stage governs several critical parameters of the freeze drying
      process and the quality of the resulting lyophilized products. This paper
      presents an integrated ultrasonic transducer (UT) in a stainless steel bottle and
      its application to real-time diagnostics of the water freezing process. The
      sensor was directly deposited onto the stainless steel bottle using a sol-gel
      spray technique. It could operate at temperature range from -100 to 400  degrees
      C and uses an ultrasonic pulse-echo technique. The progression of the freezing
      process, including water-in, freezing point and final phase change of water, were
      all clearly observed using ultrasound. The ultrasonic signals could indicate the
      three stages of the freezing process and evaluate the cooling and freezing
      periods under various processing conditions. The temperature was also adopted for
      evaluating the cooling and freezing periods. These periods increased with water
      volume and decreased with shelf temperature (i.e., speed of freezing). This study
      demonstrates the effectiveness of the ultrasonic sensor and technology for
      diagnosing and optimizing the process of water freezing to save energy. 

PMID- 25946630
TI  - WSN- and IOT-Based Smart Homes and Their Extension to Smart Buildings.
AB  - Our research approach is to design and develop reliable, efficient, flexible,
      economical, real-time and realistic wellness sensor networks for smart home
      systems. The heterogeneous sensor and actuator nodes based on wireless networking
      technologies are deployed into the home environment. These nodes generate real
      time data related to the object usage and movement inside the home, to forecast
      the wellness of an individual. Here, wellness stands for how efficiently someone
      stays fit in the home environment and performs his or her daily routine in order
      to live a long and healthy life. We initiate the research with the development of
      the smart home approach and implement it in different home conditions (different
      houses) to monitor the activity of an inhabitant for wellness detection.
      Additionally, our research extends the smart home system to smart buildings and
      models the design issues related to the smart building environment; these design
      issues are linked with system performance and reliability. This research paper
      also discusses and illustrates the possible mitigation to handle the ISM band
      interference and attenuation losses without compromising optimum system
      performance. 

PMID- 25946632
TI  - Analyzing SystemC Designs: SystemC Analysis Approaches for Varying Applications.
AB  - The complexity of hardware designs is still increasing according to Moore's law.
      With embedded systems being more and more intertwined and working together not
      only with each other, but also with their environments as cyber physical systems
      (CPSs), more streamlined development workflows are employed to handle the
      increasing complexity during a system's design phase. SystemC is a C++ library
      for the design of hardware/software systems, enabling the designer to quickly
      prototype, e.g., a distributed CPS without having to decide about particular
      implementation details (such as whether to implement a feature in hardware or in
      software) early in the design process. Thereby, this approach reduces the initial
      implementation's complexity by offering an abstract layer with which to build a
      working prototype. However, as SystemC is based on C++, analyzing designs becomes
      a difficult task due to the complex language features that are available to the
      designer. Several fundamentally different approaches for analyzing SystemC
      designs have been suggested. This work illustrates several different SystemC
      analysis approaches, including their specific advantages and shortcomings,
      allowing designers to pick the right tools to assist them with a specific problem
      during the design of a system using SystemC. 

PMID- 25946631
TI  - Field effect sensors for nucleic Acid detection: recent advances and future
      perspectives.
AB  - In the last decade the use of field-effect-based devices has become a basic
      structural element in a new generation of biosensors that allow label-free DNA
      analysis. In particular, ion sensitive field effect transistors (FET) are the
      basis for the development of radical new approaches for the specific detection
      and characterization of DNA due to FETs' greater signal-to-noise ratio, fast
      measurement capabilities, and possibility to be included in portable
      instrumentation. Reliable molecular characterization of DNA and/or RNA is vital
      for disease diagnostics and to follow up alterations in gene expression profiles.
      FET biosensors may become a relevant tool for molecular diagnostics and at point
      of-care. The development of these devices and strategies should be carefully
      designed, as biomolecular recognition and detection events must occur within the
      Debye length. This limitation is sometimes considered to be fundamental for FET
      devices and considerable efforts have been made to develop better architectures.
      Herein we review the use of field effect sensors for nucleic acid detection
      strategies-from production and functionalization to integration in molecular
      diagnostics platforms, with special focus on those that have made their way into
      the diagnostics lab. 

PMID- 25946633
TI  - Fabrication and robotization of ultrasensitive plasmonic nanosensors for molecule
      detection with Raman scattering.
AB  - In this work, we introduce the history and mechanisms of surface enhanced Raman
      scattering (SERS), discuss various techniques for fabrication of state-of-the-art
      SERS substrates, and review recent work on robotizing plasmonic nanoparticles,
      especially, the efforts we made on fabrication, characterization, and
      robotization of Raman nanosensors by design. Our nanosensors, consisting of tri
      layer nanocapsule structures, are ultrasensitive, well reproducible, and can be
      robotized by either electric or magnetic tweezers. Three applications using such
      SERS nanosensors were demonstrated, including location predictable detection,
      single-cell bioanalysis, and tunable molecule release and monitoring. The
      integration of SERS and nanoelectromechanical system (NEMS) devices is innovative
      in both device concept and fabrication, and could potentially inspire a new
      device scheme for various bio-relevant applications. 

PMID- 25946634
TI  - Dynamic response of tapered optical multimode fiber coated with carbon nanotubes
      for ethanol sensing application.
AB  - Ethanol is a highly combustible chemical universally designed for biomedical
      applications. In this paper, optical sensing performance of tapered multimode
      fiber tip coated with carbon nanotube (CNT) thin film towards aqueous ethanol
      with different concentrations is investigated. The tapered optical multimode
      fiber tip is coated with CNT using drop-casting technique and is annealed at 70 
      degrees C to enhance the binding of the nanomaterial to the silica fiber tip. The
      optical fiber tip and the CNT sensing layer are micro-characterized using FESEM
      and Raman spectroscopy techniques. When the developed sensor was exposed to
      different concentrations of ethanol (5% to 80%), the sensor reflectance reduced
      proportionally. The developed sensors showed high sensitivity, repeatability and
      fast responses (<55 s) towards ethanol. 

PMID- 25946635
TI  - Towards a dynamic clamp for neurochemical modalities.
AB  - The classic dynamic clamp technique uses a real-time electrical interface between
      living cells and neural simulations in order to investigate hypotheses about
      neural function and structure. One of the acknowledged drawbacks of that
      technique is the limited control of the cells' chemical microenvironment. In this
      manuscript, we use a novel combination of nanosensor and microfluidic technology
      and microfluidic and neural simulations to add sensing and control of chemical
      concentrations to the dynamic clamp technique. Specifically, we use a
      microfluidic lab-on-a-chip to generate distinct chemical concentration gradients
      (ions or neuromodulators), to register the concentrations with embedded
      nanosensors and use the processed signals as an input to simulations of a neural
      cell. The ultimate goal of this project is to close the loop and provide sensor
      signals to the microfluidic lab-on-a-chip to mimic the interaction of the
      simulated cell with other cells in its chemical environment. 

PMID- 25946636
TI  - Peramivir is as effective as oral oseltamivir in the treatment of severe seasonal
      influenza.
AB  - The clinical efficacy of peramivir in the treatment of severe seasonal influenza
      in critically ill patients admitted to an intensive care unit (ICU) is not well
      established. The aim of this study was to compare the clinical efficacy of
      peramivir with that of oseltamivir in such critically ill patients. From
      September 2010 through March 2014, sixty patients with influenza confirmed by RT
      PCR and hospitalized in our ICU were enrolled and reviewed retrospectively.
      Thirty-four and twenty-six patients received initial peramivir and oseltamivir,
      respectively. The median sequential organ failure assessment score was higher in
      the patients treated with peramivir (11 vs. 8.5, P= 0.029). There was no
      significant difference between the two groups in the median duration of use of
      antiviral agents. There were also no significant differences between the groups
      in 14-day (17.6% in peramivir vs. 7.7% in oseltamivir, P = 0.446), or 28-day
      mortality (35.3% in peramivir vs. 34.6% in oseltamivir, P = 0.813) or in the
      median length of ICU stay (11 days in peramivir vs. 12 days in oseltamivir,
      P=0.852). Peramivir has the similar clinical efficacy to oseltamivir in the
      treatment of severe seasonal influenza in the critically ill patients admitted to
      ICU.

PMID- 25946637
TI  - Bioremediation of Atmospheric Hydrocarbons via Bacteria Naturally Associated with
      Leaves of Higher Plants.
AB  - Bacteria associated with leaves of sixteen cultivated and wild plant species from
      all over Kuwait were analyzed by a culture-independent approach. This technique
      depended on partial sequencing of 16S rDNA regions in total genomic DNA from the
      bacterial consortia and comparing the resulting sequences with those in the
      GenBank database. To release bacterial cells from leaves, tough methods such as
      sonication co-released too much leaf chloroplasts whose DNA interfered with the
      bacterial DNA. A more satisfactory bacterial release with a minimum of
      chloroplast co-release was done by gently rubbing the leaf surfaces with soft
      tooth brushes in phosphate buffer. The leaves of all plant species harbored on
      their surfaces bacterial communities predominated by hydrocarbonoclastic
      (hydrocarbon-utilizing) bacterial genera. Leaves of 6 representative plants
      brought about in the laboratory effective removal of volatile hydrocarbons in
      sealed microcosms. Each individual plant species had a unique bacterial community
      structure. Collectively, the phyllospheric microflora on the studied plants
      comprised the genera Flavobacterium, Halomonas, Arthrobacter, Marinobacter,
      Neisseria, Ralstonia, Ochrobactrum. Exiguobacterium, Planomicrobium,
      Propionibacterium, Kocuria, Rhodococcus and Stenotrophomonas. This community
      structure was dramatically different from the structure we determined earlier for
      the same plants using the culture-dependent approach, although in both cases,
      hydrocarbonoclastic bacteria were frequent. 

PMID- 25946638
TI  - Superparamagnetic Fe(OH)3@Fe3O4 Nanoparticles: An Efficient and Recoverable
      Catalyst for Tandem Oxidative Amidation of Alcohols with Amine Hydrochloride
      Salts.
AB  - Magnetic Fe(OH)3@Fe3O4 nanoparticles were successfully prepared and
      characterized. This magnetic nanocomposite was employed as an efficient,
      reusable, and environmentally benign heterogeneous catalyst for the direct
      amidation of alcohols with amine hydrochloride salts. Several derivatives of
      primary, secondary and tertiary amides were synthesized in moderate to good
      yields in the presence of this catalytic system. The catalyst was successfully
      recycled and reused up to six times without significant loss of its catalytic
      activity. 

PMID- 25946639
TI  - Physicochemical Characteristics and Slow Release Performances of Chlorpyrifos
      Encapsulated by Poly(butyl acrylate-co-styrene) with the Cross-Linker Ethylene
      Glycol Dimethacrylate.
AB  - Chlorpyrifos' application and delivery to the target substrate needs to be
      controlled to improve its use. Herein, poly(butyl acrylate-co-styrene)
      (poly(BA/St)) and poly(BA/St/ethylene glycol dimethacrylate (EGDMA))
      microcapsules loaded with chlorpyrifos as a slow release formulation were
      prepared by emulsion polymerization. The effects of structural characteristics on
      the chlorpyrifos microcapsule particle size, entrapment rate (ER), pesticide
      loading (PL), and release behaviors in ethyl alcohol were investigated. Fourier
      transform infrared and thermogravimetric analysis confirmed the successful
      entrapment of chlorpyrifos. The ER and PL varied with the BA/St monomer ratio,
      chlorpyrifos/monomer core-to-shell ratio, and EGDMA cross-linker content with
      consequence that suitable PL was estimated to be smaller than 3.09% and the
      highest ER was observed as 96.74%. The microcapsule particle size (88.36-101.8
      nm) remained mostly constant. The extent of sustainable release decreased with
      increasing content of BA, St, or chlorpyrifos in the oil phase. Specifically, an
      adequate degree of cross-linking with EGMDA (0.5-2.5%) increased the extent of
      sustainable release considerably. However, higher levels of cross-linking with
      EGDMA (5-10%) reduced the extent of sustainable release. Chlorpyrifos release
      from specific microcapsules (monomer ratio 1:2 with 0.5% EGDMA or 5 g
      chlopyrifos) tended to be a diffusion-controlled process, while for others, the
      kinetics probably indicated the initial rupture release. 

PMID- 25946640
TI  - Aged persons mental health service in rural Victoria.

PMID- 25946641
TI  - Origins of the Intermediate Spectral Form in M100 Mutants of Photoactive Yellow
      Protein.
AB  - Numerous single-site mutants of photoactive yellow protein (PYP) from
      Halorhodospira halophila and as well as PYP homologs from other species exhibit a
      shoulder on the short wavelength side of the absorbance maximum in their dark
      adapted states. The structural basis for the occurrence of this shoulder, called
      the "intermediate spectral form," has only been investigated in detail for the
      Y42F mutation. Here we explore the structural basis for occurrence of the
      intermediate spectral form in a M121E derivative of a circularly permuted H.
      halophila PYP (M121E-cPYP). The M121 site in M121E-cPYP corresponds to the M100
      site in wild-type H. halophila PYP. High-resolution NMR measurements with a salt
      tolerant cryoprobe enabled identification of those residues directly affected by
      increasing concentrations of ammonium chloride, a salt that greatly enhances the
      fraction of the intermediate spectra form. Residues in the surface loop
      containing the M121E (M100E) mutation were found to be affected by ammonium
      chloride as well as a discrete set of residues that link this surface loop to the
      buried hydroxyl group of the chromophore via a hydrogen bond network. Localized
      changes in the conformational dynamics of a surface loop can thereby produce
      structural rearrangements near the buried hydroxyl group chromophore while
      leaving the large majority of residues in the protein unaffected. 

PMID- 25946642
TI  - Single-Incision Laparoscopic Splenectomy Using the Suture Suspension Technique
      for Splenomegaly in Children with Hereditary Spherocytosis.
AB  - BACKGROUND: With increasing laparoscopic surgery experience and improved new
      vessel-sealing equipment, single-incision laparoscopic surgery (SILS) for
      splenectomy has emerged as an alternative to multiport laparoscopy, but the
      application of SILS for splenomegaly is still challenging due to technical
      difficulties. The aim of this study was to describe the suture suspension
      technique contributing to SILS for hereditary spherocytosis (HS). MATERIALS AND
      METHODS: A retrospective review was conducted to evaluate all SILS for
      splenomegaly performed by a single surgeon. On preoperative ultrasonography, the
      spleen size index ranged from 0.67 to 0.82. An umbilical incision was used for
      the placement of a multichannel single port. To provide excellent exposure of the
      splenic hilum, a needle with a 1-0 suture was percutaneously introduced from the
      left hypochondriac region and then penetrated out the anterior chest wall for
      suspending the enlarged spleen. Dissection was facilitated by the use of a 5-mm
      curved reusable grasper and a 5-mm Harmonic((r)) scalpel (Ethicon Endo-Surgery,
      Cincinnati, OH), and the splenic vessels were ligated with 5-mm Weck((r)) Hem-o
      lok((r)) clips (Teleflex((r)), Morrisville, NC). The resected spleen was placed
      in an endosurgical bag, morcellated, and removed from the abdomen via the
      umbilical incision. RESULTS: Nine children underwent SILS during the study period
      without conversion to open procedures or requiring additional ports. The suture
      suspension technique was successfully used and markedly improved the exposure of
      the splenic hilum. The operative time was 122.6 +/- 31.2 minutes, and the
      extracted spleen weight was 562 +/- 74.5 g (range, 420-1260 g). No intraoperative
      or postoperative complications were recorded. The umbilical incision healed well
      with a satisfactory cosmetic effect. CONCLUSIONS: Our outcome shows the suture
      suspension enables safe and feasible usage of SILS for the management of
      splenomegaly in children with HS. More experience is needed to assess advantages
      and disadvantages compared with the standard laparoscopic approach.

PMID- 25946644
TI  - Sleep and health implications of snoring: A populational analysis.
AB  - OBJECTIVES/HYPOTHESIS: Determine the prevalence of snoring and if snoring is
      associated with negative effects on sleep patterns and other health conditions.
      STUDY DESIGN: Cross-sectional analysis of large-scale national risk-factor
      survey. METHODS: The Behavioral Risk Factor Surveillance System for the 2012
      sleep health component was analyzed to determine the relationships between
      respondents' sleep patterns including average hours slept, days of insufficient
      sleep, falling asleep while driving, and the presence of snoring. The
      associations between snoring and coronary artery disease, stroke, and depressive
      disorder were also determined. RESULTS: Among 8,137,604 weighted respondents (raw
      N = 22,745), 52.8% (95% confidence interval, 51.9%-53.8%) reported that they
      snored. Males were more likely to report snoring than females (59.0% vs. 46.9%,
      respectively, P < .001) and increasing body mass index was associated with a
      higher prevalence of snoring (normal weight, 36% snoring vs. obese, 71%; P <
      .001). Snorers reported decreased sleep time, more lack of sleep days, and
      unintentional falling asleep days than nonsnorers (6.97 vs. 7.15 hours, 9.1 vs.
      7.6 days, and 3.3 vs. 2.1 days, respectively; all P < .001). Snorers were more
      likely to have fallen asleep while driving than nonsnorers (odds ratio, 1.49; P <
      .001). Snorers also demonstrated increased odds ratios for coronary artery
      disease and depressive disorder (odds ratios 1.40 and 1.39; respectively, P <
      .001), but not for stroke (P = .421). CONCLUSIONS: Self-reported snoring is
      associated with significant negative sleep pattern behaviors as well as coronary
      artery disease and depressive disorders. Further study of snoring as a risk
      factor for poor sleep and other diseases is warranted. LEVEL OF EVIDENCE: 2c

PMID- 25946643
TI  - Ras transformation results in cleavage of reticulon protein Nogo-B that is
      associated with impairment of IFN response.
AB  - Dysregulation of Ras signaling is the major cause of various cancers. Aberrant
      Ras signaling, however, provides a favorable environment for many viruses, making
      them suitable candidates as cancer-killing therapeutic agents. Susceptibility of
      cancer cells to such viruses is mainly due to impaired type I interferon (IFN)
      response, often as a result of activated Ras/ERK signaling in these cells. In
      this study, we searched for cellular factors modulated by Ras signaling and their
      potential involvement in promoting viral oncolysis. We found that upon Ras
      transformation of NIH-3T3 cells, the N-terminus of Nogo-B (reticulon 4) was
      proteolytically cleaved. Interestingly, Nogo knockdown (KD) in non-transformed
      and Ras-transformed cells both enhanced virus-induced IFN response, suggesting
      that both cleaved and uncleaved Nogo can suppress IFN response. However,
      pharmacological blockade of Nogo cleavage in Ras-transformed cells significantly
      enhanced virus-induced IFN response, suggesting that cleaved Nogo contributes to
      enhanced IFN suppression in these cells. We further showed that IFN suppression
      associated with Ras-induced Nogo-B cleavage was distinct from but synergistic
      with that associated with an activated Ras/ERK pathway. Our study therefore
      reveals an important and novel role of Nogo-B and its cleavage in the suppression
      of anti-viral immune responses by oncogenic Ras transformation. 

PMID- 25946645
TI  - Thiocyanation of BODIPY dyes and their conversion to thioalkylated derivatives.
AB  - A high-yielding method for the direct thiocyanation of BODIPY dyes is described.
      In 1,3-dimethyl BODIPYs, the thiocyanato group adds at position 2, whereas the
      insertion occurs at position 5 in 3-amino BODIPYs. The transformation of the
      thiocyanato group enables the synthesis of thioalkylated BODIPYs. 2-Thioalkylated
      BODIPYs and 3-thiocyanato-5-piperidino BODIPYs exhibit interesting
      spectroscopical features. Hence, the described synthetic methodology can be used
      for the photophysical tuning of BODIPY dyes. 

PMID- 25946646
TI  - Idiopathic pulmonary fibrosis: Recent advances on pharmacological therapy.
AB  - Idiopathic pulmonary fibrosis (IPF) is the most common and lethal of the
      idiopathic interstitial pneumonias with an estimated 5-year survival of
      approximately 20%. In the last two decades our understanding of disease
      pathogenesis has substantially evolved and novel compounds have been developed
      consequent to the increasing knowledge of the mechanisms underlying disease
      pathobiology. The disease appears to be driven - following chronic injury - by
      abnormal/dysfunctional alveolar epithelial cells that promote fibroblast
      recruitment and proliferation, resulting in scarring of the lung and irreversible
      loss of function. With very few exceptions, clinical trials evaluating novel
      potential therapies have provided disappointing results. More recently,
      pirfenidone and nintedanib, two compounds with pleiotropic mechanisms of action,
      have proven effective in slowing functional decline and disease progression in
      IPF patients with mild to moderate functional impairment, highlighting the
      importance of timely diagnosis and administration of treatment in early stages of
      disease. However, due to the complexity and uncertainties intrinsic to IPF, it is
      essential that each therapeutic strategy be tailored to the individual patient,
      after evaluation of potential benefits and risks. This article provides an
      overview of the most recent clinical trials in IPF and discusses how their
      results are going to change the clinical and clinical research landscape in IPF.
      A number of agents with high potential are currently being tested and many more
      are ready for clinical trials. Their completion is critical for achieving the
      ultimate goal of curing patients with IPF. 

PMID- 25946647
TI  - A retrospective comparison of older and younger adults undergoing early
      laparoscopic cholecystectomy for mild to moderate calculous cholecystitis.
AB  - OBJECTIVES: To compare the demographic characteristics and intra- and
      postoperative outcomes in elderly adults (>=75) with those of younger adults
      undergoing early (<5 days after onset of complaints) cholecystectomy. DESIGN:
      Retrospective analysis from May 2010 to August 2012. SETTING: Randomized,
      multicenter, clinical trial (ABCAL Study, NCT01015417). PARTICIPANTS: Individuals
      with mild or moderate acute calculous cholecystitis (ACC) according to the Tokyo
      Guidelines (N=414; n=78 aged 75-94, median 82; n=336 aged 18-74, median 49).
      MEASUREMENTS: Demographic characteristics and pre-, intra-, and postoperative
      data. RESULTS: The elderly group was more likely to have an American Society of
      Anesthesiologists score of 3 or greater (62% vs 23%, P<.001), higher serum
      creatinine (103 vs 74 MUmol/L, P<.001), and more-severe ACC (moderate ACC (62% vs
      50%, P=.05), gangrenous cholecystitis (38% vs 15%, P=.001)) on preoperative
      imaging and confirmed intraoperatively. Ulcerated mucosa (76% vs 61%, P=.001) was
      significantly more frequent in the elderly group. Operative time, postoperative
      mortality, and postoperative infectious (18% vs 14%, P=.35) and noninfectious (9%
      vs 3%, P=.80) complications were similar between the two groups. Median length of
      stay (7.0 vs 5.0 days, P=.54) and readmission rate (15% vs 4%, P=.07) were not
      significantly higher in the elderly group. No significant difference was observed
      for the subgroup of participants aged 80 and older. CONCLUSION: In this
      randomized trial that included a selected sample of older adults, there was no
      difference in major outcomes between elderly adults and their younger
      counterparts after early cholecystectomy. The findings are limited because
      important geriatric outcomes such as delirium and functional decline were not
      examined.

PMID- 25946648
TI  - Cysteine sulfur chemistry in transcriptional regulators at the host-bacterial
      pathogen interface.
AB  - Hosts employ myriad weapons to combat invading microorganisms as an integral
      feature of the host-bacterial pathogen interface. This interface is dominated by
      highly reactive small molecules that collectively induce oxidative stress.
      Successful pathogens employ transcriptional regulatory proteins that sense these
      small molecules directly or indirectly via a change in the ratio of reduced to
      oxidized low-molecular weight (LMW) thiols that collectively comprise the redox
      buffer in the cytoplasm. These transcriptional regulators employ either a
      prosthetic group or reactive cysteine residue(s) to effect changes in the
      transcription of genes that encode detoxification and repair systems that is
      driven by regulator conformational switching between high-affinity and low
      affinity DNA-binding states. Cysteine harbors a highly polarizable sulfur atom
      that readily undergoes changes in oxidation state in response to oxidative stress
      to produce a range of regulatory post-translational modifications (PTMs),
      including sulfenylation (S-hydroxylation), mixed disulfide bond formation with
      LMW thiols (S-thiolation), di- and trisulfide bond formation, S-nitrosation, and
      S-alkylation. Here we discuss several examples of structurally characterized
      cysteine thiol-specific transcriptional regulators that sense changes in cellular
      redox balance, focusing on the nature of the cysteine PTM itself and the
      interplay of small molecule oxidative stressors in mediating a specific
      transcriptional response. 

PMID- 25946649
TI  - Design of an endovascular morcellator for the surgical treatment of equine
      Cushing's disease.
AB  - BACKGROUND: A new paradigm of surgical treatment of equine Cushing's disease has
      been developed using the vascular system combined with a flexible morcellation
      instrument to reach the pituitary gland. OBJECTIVE: The goal was twofold: (1) to
      design, prototype, and test an instrument that can reach the pituitary gland
      using the vascular system unique to equids and (2) to test the feasibility of the
      endovascular approach. ANIMALS AND METHODS: The morcellator consists of a radial
      rotating cutting blade for tissue resection, a flexible shaft incorporating a
      cable drive for flexible actuation, and central morcellated tissue transportation
      lumen. The morcellator prototype was tested on a horse's cadaver head for the
      validation of the cutting blade design, actuator design, and feasibility of the
      endovascular approach. RESULTS: The overall assembled length of the morcellator
      tip was 13.9 mm, allowing for non-traumatic steering through the vascular system
      from the proximal end. The radially rotating cutting blade (barrel of O 4 and 4.4
      mm width) incorporated multiple cutting edges to deliver the action force during
      resection and provides the necessary grasping force to draw the tissue towards
      the second cutting edge of the morcellator incorporated inside the blunted
      cuboidal static tip element (5 mm square and wall-thickness of 0.3 mm). In the
      tests, the morcellator was successfully guided towards the pituitary and managed
      to sample pituitary tissue. CONCLUSION AND CLINICAL IMPORTANCE: Continued
      development of the prototype and the endovascular approach may in time improve
      the outcome and quality of life of horses suffering from Cushing's disease.

PMID- 25946650
TI  - Ridge regeneration of damaged extraction sockets using rhBMP-2: an experimental
      study in canine.
AB  - OBJECTIVES: This study evaluated the dimensional ridge alteration in a buccal
      bone-deficient extraction socket, and ridge regeneration following socket
      grafting accompanied by recombinant human bone morphogenetic protein 2 (rhBMP-2)
      or a collagen membrane covering. MATERIAL AND METHODS: In five beagle dogs,
      entire buccal bone of the extracted sockets of premolars was surgically removed
      and immediately grafted using one of the following graft protocols: (1) sham
      surgery without any grafting, and grafting with (2) deproteinized bovine bone
      mineral (DBBM), (3) DBBM/rhBMP-2 and (4) DBBM covered with a collagen membrane
      (DBBM/Membrane). Quantitative/qualitative analyses were performed
      radiographically/histologically after 8 weeks. RESULTS: Buccal-deficient
      extraction sockets healed with significant reduction in buccolingual dimension
      along the entire length of the socket, but all grafting techniques reduced the
      dimensional changes compared to the non-grafted control sites. Histologically,
      sites received DBBM only exhibited minimal regeneration, whereas sites grafted
      with DBBM/rhBMP-2 or DBBM/Membrane exhibited greater new bone formation extending
      the entire augmented area. CONCLUSIONS: Buccal-bone-deficiency may lead to
      significant volume reduction after tooth extraction along the entire length of
      the socket, and socket grafting accompanied by rhBMP-2 or covered with a membrane
      can be candidate therapies for preservation of the buccolingual dimension and
      successful ridge regeneration.

PMID- 25946652
TI  - Implementation of a rapid chest pain protocol in the emergency department: A
      quality improvement project.
AB  - PURPOSE: The purpose of this quality improvement (QI) project is to compare the
      effectiveness of a rapid 90-min chest pain screening and evaluation protocol to a
      120-min screening and evaluation protocol in determining patient readiness for
      hospital admission or discharge home. DATA SOURCES: The existing chest pain
      protocol utilized in the emergency department (ED) was revised based on a review
      of current research changing initial screening and reevaluation times from 120 to
      90 min. A prospective comparative study of patients presenting to the ED with
      chest pain was performed comparing the existing chest pain protocol of 120 min
      (standard care) with a rapid screening evaluation protocol of 90 min. A total of
      128 patients presenting to an ED in Texas with chest pain comprised the sample
      for this study. CONCLUSIONS: There was a significant difference in the number of
      minutes between the groups for readiness for disposition. The average time from
      chest pain evaluation to readiness for disposition home, observation, or
      admission decreased from an average of 191 min in the standard care group to an
      average of 118 min in the rapid screening group. IMPLICATIONS FOR PRACTICE: Use
      of the rapid screening and evaluation protocol decreased the time to disposition
      by an average of 73 min, which enhanced ED flow without influencing disposition
      and patient safety.

PMID- 25946651
TI  - Dissecting the calcium-induced differentiation of human primary keratinocytes
      stem cells by integrative and structural network analyses.
AB  - The molecular details underlying the time-dependent assembly of protein complexes
      in cellular networks, such as those that occur during differentiation, are
      largely unexplored. Focusing on the calcium-induced differentiation of primary
      human keratinocytes as a model system for a major cellular reorganization
      process, we look at the expression of genes whose products are involved in
      manually-annotated protein complexes. Clustering analyses revealed only moderate
      co-expression of functionally related proteins during differentiation. However,
      when we looked at protein complexes, we found that the majority (55%) are
      composed of non-dynamic and dynamic gene products ('di-chromatic'), 19% are non
      dynamic, and 26% only dynamic. Considering three-dimensional protein structures
      to predict steric interactions, we found that proteins encoded by dynamic genes
      frequently interact with a common non-dynamic protein in a mutually exclusive
      fashion. This suggests that during differentiation, complex assemblies may also
      change through variation in the abundance of proteins that compete for binding to
      common proteins as found in some cases for paralogous proteins. Considering the
      example of the TNF-alpha/NFkappaB signaling complex, we suggest that the same
      core complex can guide signals into diverse context-specific outputs by addition
      of time specific expressed subunits, while keeping other cellular functions
      constant. Thus, our analysis provides evidence that complex assembly with stable
      core components and competition could contribute to cell differentiation. 

PMID- 25946653
TI  - Hypromellose-graft-chitosan and Its Polyelectrolyte Complex as Novel Systems for
      Sustained Drug Delivery.
AB  - Polyelectrolyte complexes formed between chitosan (CS) and anionic polymers have
      attracted increasing interest in drug delivery. In this study, CS is
      copolymerized with hypromellose via a coupling reagent-mediated approach to form
      a water-soluble, nontoxic CS derivative, namely hypromellose-graft-CS (HC), which
      is subsequently complexed with carboxymethylcellulose (CMC) to generate a
      polyampholytic hydrogel. When compared with conventional CS, HC is highly water
      soluble across a wide pH range, and has a substantially higher pH buffering
      capacity to provide a pH-stable environment for delivery of drugs. In addition,
      the polyelectrolyte complex of HC exhibits a drug encapsulation efficiency of
      over 90% in all drugs tested, which is 1-2 fold higher than the efficiency
      attainable by the polyelectrolyte complex of conventional CS, with a 2-3 fold
      longer duration of sustained drug release. Our results indicate that as a novel
      polymer, HC has excellent promise for future pharmaceutical applications. 

PMID- 25946654
TI  - NLRP3 inflammasome in peripheral blood monocytes of acute coronary syndrome
      patients and its relationship with statins.
AB  - OBJECTIVES: Despite recent advances in the understanding of the role of NLRP3
      inflammasomes in coronary atherosclerosis, further work on their activation and
      clinical implications remains to be performed. In this study, we aimed to
      evaluate the effect of the dose of rosuvastatin on NLRP3 and cathepsin-B
      expression in peripheral blood monocytes in patients with acute coronary
      syndrome. METHODS: A total of 123 participants were enrolled in this study; these
      included acute myocardial infarction (AMI) patients (n=53), unstable angina
      patients (UA, n=40), and normal controls (n=30). AMI and UA patients were divided
      into high-dose rosuvastatin (20 mg) and low-dose rosuvastatin (5 mg) groups.
      NLRP3, cathepsin-B, and downstream cytokine expressions were appropriately
      evaluated using real-time PCR, flow cytometry, western blotting and enzyme-linked
      immunosorbent assay. The concentrations of serum inflammatory markers were also
      evaluated for correlation with NLRP3 levels. RESULTS: AMI and UA patients had
      higher NLRP3, cathepsin-B, interleukin-18 (IL-18), pro-IL-18, IL-1beta, and pro
      IL-1beta expressions as compared with the control group (P<0.05). This
      corresponded with higher levels of serum total cholesterol, serum low-density
      lipoprotein cholesterol, and oxidized low-density lipoprotein in UA and AMI
      patients (P<0.05). Rosuvastatin at a concentration of 20 mg led to a significant
      decrease (P<0.05) in the expressions of NLRP3, cathepsin-B, and their downstream
      cytokines as compared with 5 mg rosuvastatin (P>0.05) from baseline to 4 weeks.
      This study also showed a positive correlation between NLRP3, cathepsin-B, and
      downstream inflammatory mediators. CONCLUSION: NLRP3 is involved in inflammation
      that leads to atherosclerosis. A high dose of rosuvastatin can modulate the
      inflammatory process of atherosclerosis by downregulating the expression of
      NLRP3, cathepsin-B, and their downstream mediators. These findings provide
      insight into the pathogenesis and management of acute coronary syndrome, with
      NLRP3 as the potential target.

PMID- 25946655
TI  - Low 25-OH vitamin D levels are not associated with coronary artery calcium or
      obstructive stenoses.
AB  - BACKGROUND: It is unclear whether low vitamin D is a significant risk factor for
      the presence of either calcific atherosclerosis or obstructive coronary artery
      stenoses. DESIGN: In this study, we measured the 25-OH vitamin D levels of 1131
      consecutive individuals who underwent coronary artery calcium (CAC) scoring and
      coronary computed tomographic angiography at our institution. PARTICIPANTS AND
      METHODS: We looked for any association of 25-OH vitamin D levels with CAC scores.
      We also studied the relation of 25-OH vitamin D levels with the presence of 70%
      or more obstructive coronary artery stenoses, found initially by coronary
      computed tomographic angiography and confirmed subsequently by invasive
      angiography. RESULTS: There were 132 (11.7%) 25-OH vitamin D deficient (<20
      ng/ml) and 295 (26.1%) 25-OH vitamin D insufficient (21-29 ng/ml) individuals in
      this study. There was no detectable association between 25-OH vitamin D levels
      and CAC scores. The median (interquartile range) CAC score of 25-OH vitamin D
      deficient, insufficient, and adequate patients was 451 (80-1083), 338 (52-830),
      and 450 (100-1062), respectively. Also, no relation was noted between 25-OH
      vitamin D levels and the presence of severely obstructive coronary artery
      disease. The frequency of severe coronary artery disease in 25-OH vitamin D
      deficient, insufficient, and adequate patients was 3.8, 2.0, and 4.0%,
      respectively. CONCLUSION: Low 25-OH vitamin D levels were not associated with CAC
      or severely obstructive stenoses.

PMID- 25946657
TI  - Pancreatic cancer control: is vitamin D the answer?
AB  - Pancreatic cancer is characterized by late detection, resistance to therapy, poor
      prognosis, and an exceptionally high mortality rate. Epidemiology ascribes a
      chemopreventive role to vitamin D in several cancers including pancreatic cancer.
      Vitamin D therapy has been ascribed a role previously in tumor inhibition and
      differentiation in addition to reduction of inflammation and angiogenesis.
      However, the role of vitamin D in pancreatic cancer prevention or therapy remains
      elusive to date. Studies have shown a negative correlation between the risk of
      pancreatic cancer and serum vitamin D levels. It is believed that vitamin D
      binding to certain conserved sequences called vitamin D response elements in the
      DNA can alter the expression of genes involved in tumorigenesis. Recent research
      has elucidated the role of zinc in carcinogenesis, which in turn is found to be
      affected by vitamin D supplementation. In the light of numerous new-found roles
      for vitamin D, we review and evaluate the potential actions of the sunshine
      vitamin with respect to pancreatic cancer prevention and therapy. 

PMID- 25946656
TI  - Current developments and future applications of intracoronary hemodynamics.
AB  - Intracoronary hemodynamic assessment of the physiologic significance of coronary
      lesions improves clinical outcomes in patients with coronary artery disease.
      Coronary flow velocity reserve, fractional flow reserve, instantaneous wave-free
      ratio, and index of microcirculatory resistance utilize sensor-mounted guidewires
      to approximate coronary flow. Coronary flow velocity reserve and fractional flow
      reserve rely on pharmacologic administration of adenosine to achieve hyperemia
      and diagnose epicardial lesion severity. As an adenosine-free index, the
      instantaneous wave-free ratio utilizes a wave-free period in the mid-late
      diastole during which resistance is constant and low to assess lesion
      significance. The index of microcirculatory resistance combines hyperemic
      pressure measurements with thermodilution to quantify microvascular resistance.
      We review the physiology, clinical trials, and clinical applications of these
      invasive hemodynamic assessments. 

PMID- 25946658
TI  - Psychometric properties of an Australian supportive care needs assessment tool
      for Indigenous patients with cancer.
AB  - BACKGROUND: There are significant disparities in cancer outcomes between
      Indigenous and non-Indigenous Australians. Identifying the unmet supportive care
      needs of Indigenous Australians with cancer is imperative to improve their cancer
      care. The purpose of the current study was to test the psychometric properties of
      a supportive cancer care needs assessment tool for Indigenous people (SCNAT-IP)
      with cancer. METHODS: The SCNAT-IP was administered to 248 Indigenous Australians
      diagnosed with a range of cancer types and stages, and who received treatment in
      1 of 4 Queensland hospitals. All 39 items were assessed for ceiling and floor
      effects and were analyzed using exploratory factor analysis to determine
      construct validity. Identified factors were assessed for internal consistency and
      convergent validity to validated psychosocial tools. RESULTS: Exploratory factor
      analysis revealed a 4-factor structure (physical and psychological, hospital
      care, information and communication, and practical and cultural needs) explaining
      51% of the variance. Internal consistency of the 4 subscales was good, with
      Cronbach alpha reliability coefficients ranging from .70 to .89. Convergent
      validity was supported by significant correlations between the SCNAT-IP with the
      National Comprehensive Cancer Network Distress Thermometer (correlation
      coefficient [r] = 0.60; P<.001) and the Cancer Worry Chart (r = 0.58; P<.001) and
      a moderately strong negative correlation with the Assessment of Quality of Life
      questionnaire (r = -0.56; P<.001). CONCLUSIONS: These data provide initial
      support for the SCNAT-IP, a measure of multiple supportive care needs domains
      specific to Indigenous Australian patients with cancer undergoing treatment.

PMID- 25946659
TI  - The use of ultrasound imaging in evaluation of peritonsillar infections.
AB  - OBJECTIVES/HYPOTHESIS: The objectives of this study were to evaluate safety and
      patient tolerance of intraoral ultrasound and to evaluate efficacy of intraoral
      ultrasound in the diagnosis of peritonsillar infections. STUDY DESIGN:
      Prospective single-cohort study involving adult patients (age>18 years) with
      evaluation consistent with possible peritonsillar abscess. METHODS: Twenty-four
      patients were evaluated in the emergency department for peritonsillar infection.
      Signs and symptoms were recorded including uvular deviation, trismus, and
      fluctuance. Intraoral ultrasound was performed, and presence or absence of
      abscess was recorded. Eight patients had a computed tomography (CT) scan. Needle
      aspiration was performed by the otolaryngology physician in appropriate patients.
      Presence of purulence confirmed peritonsillar abscess. RESULTS: Intraoral
      ultrasound was successfully performed on 87.5% (21/24) of patients. The probe
      could not access the peritonsillar space in 12.5% (3/24) of patients due to
      trismus. The positive predictive value of ultrasound in diagnosing abscess was
      78.6% (11/14). The negative predictive value was 100% (7/7). The specificity was
      70% (7/10), and the sensitivity was 100% (11/11). CT scan of the neck was
      obtained in 8/24 patients and found to be 100% sensitive and specific in
      diagnosing abscess. CONCLUSIONS: Intraoral ultrasound is a sensitive imaging
      modality at our institution, making it a strong initial imaging choice in
      patients with peritonsillar infections. Ultrasound can reliably rule out the
      presence of abscess and make CT of the neck unnecessary in most patients.
      Although ultrasound is generally well tolerated, diagnosis in patients with
      severe trismus can be made clinically or with CT scan. Intraoral ultrasound is a
      useful tool in diagnosing and treating peritonsillar infections when imaging is
      required. LEVEL OF EVIDENCE: 4.

PMID- 25946660
TI  - Implant Stability Measurements in the Long-Term Follow-up of Dentis Implants: A
      Retrospective Study With Periotest.
AB  - PURPOSE: The purpose of this study was to evaluate retrospectively the stability
      of Dentis implant with the Periotest. METHODS: In total, 36 patients and 88
      implants were investigated. Periotest was used to measure implant stability, and
      a periapical view was taken immediately after surgery and again immediately
      after, 3 months after, 6 months and 5 years after prosthesis placement. Bone loss
      on the periapical view, bone quality according to tactile sensation, and area of
      implant installation were assessed. RESULTS: The mean Periotest value (PTV)
      immediately after surgery was -1.02, and the mean bone loss rate (bone
      loss/fixture length * 100) at 6 months after prosthesis placement was 8.42%. PTV
      was higher with more bone loss (types III, IV vs types I, II bone). The lowest
      mean PTV was in the lower molar area (-1.48), followed by the lower anterior (
      1.41), upper molar (0.11), and upper anterior area (5). One implant failed and
      survival rates were 98.9%. CONCLUSION: Implant stability was lower in cases with
      more bone loss and poor bone quality and in the maxilla versus the mandible.

PMID- 25946661
TI  - Measure bone volume and density changes of sites grafted with bone allografts and
      a titanium mesh on cone-beam computed tomography: a technique.
AB  - PURPOSE: The aim of this study was to introduce a novel method to evaluate
      volumetric and density changes of the augmented sites. MATERIALS AND METHODS: A
      ridge augmentation procedure, using particulate bone allografts and a titanium
      mesh, was performed on the posterior edentulous mandible of 3 participants. Cone
      beam computed tomography was taken preoperatively (1st scan), immediately (2nd
      scan), and 5 months (3rd scan) after the surgery. The grafted area was segmented
      on the 2nd and 3rd scans, using the 1st scan as the reference. The volume of the
      grafted area and the newly formed bone-graft complex that is defined by a
      preselected threshold was then determined. The bone mineral density (BMD) of the
      grafted area was determined by comparing gray-scale histograms of the grafted
      area for the 2nd and 3rd scans using the cortical bone adjacent to the grafted
      area as the reference. RESULTS: The mean volumetric shrinkage was 13.5%. The BMD
      increase was 4.65%. The mean error in determining cortical bone density between
      the scans was 1.69%. CONCLUSIONS: A novel technique to measure bone volume and
      density changes after bone augmentation was described. The low
      measurement/scanning error suggested that this technique is reliable and
      reproducible.

PMID- 25946662
TI  - Computed Tomography Findings of Mandibular Nutrient Canals.
AB  - INTRODUCTION: The purpose of this study was to assess computed tomography (CT)
      findings of mandibular nutrient canals using CT images. MATERIALS AND METHODS: We
      retrospectively analyzed the mandibular CT images of 194 consecutive patients.
      For image analysis such as canal prevalence, location, number, size, shape, and
      the CT value of nutrient foramina were determined using CT axial images of 0.5
      and 3 mm slice thickness. RESULTS: We revealed that the nutrient canals were seen
      94.3% in the mandible, mostly seen in the anterior region. By location, nutrient
      canals were particularly seen between the central and lateral incisors. The mean
      number of nutrient canals was 2.7. The mean diameter of the nutrient foramen
      between the central and lateral incisors was 1.0 mm. In about 80% of the cases,
      foramina between the central and lateral incisors were ovoid. The mean CT value
      for the nutrient foramina between the central and lateral incisors was 411 HU.
      DISCUSSION AND CONCLUSIONS: Mandibular nutrient canals were ovoid shape, and the
      mean CT value was 411 HU. By preoperative knowledge of the position and anatomy
      of the mandibular nutrient canals, complications such as injury to the nutrient
      canals can be avoided.

PMID- 25946663
TI  - Rapid Osseointegration of Titanium Implant With Innovative Nanoporous Surface
      Modification: Animal Model and Clinical Trial.
AB  - OBJECTIVES: SLAffinity is the hybrid topography consisting of micropits and
      nanoporous TiO2 layers through electrochemical oxidation to mimic the natural
      bony environment. The aim of this study was to examine the rate of
      osseointegration in animal models and to further investigate the stability for
      implants with SLAffinity-treated surface in the clinical trial. MATERIALS AND
      METHODS: Implants were installed in the mandibular canine-premolar area of 12
      miniature pigs. Each pig received 2 implants with the same shapes but with
      different chemical surfaces. In the clinical trial, 25 patients were included.
      Each patient received 1 SLAffinity-treated implant on the posterior area of
      either arch. Resonance frequency analysis and computed tomography were assessed
      weekly over the first 12 weeks after implant placement. RESULTS: The results
      found that surface treatment did affect the bone-to-implant contact (BIC)
      significantly. Comparison of BIC at 3 weeks in animal study showed that the
      SLAffinity-treated implants presented significantly higher values than machine
      surface implants. SLAffinity-treated implants also proved clinically successful
      through 12 months, ready for prosthodontic restoration. CONCLUSION: The effect of
      SLAffinity treatments enhanced osseointegration significantly, especially at
      early stages of bone healing. Clinical trial finding, furthermore, ensured that
      the SLAffinity treatment was a reliable surface modification alternative.

PMID- 25946666
TI  - Selectively splitting a droplet using superhydrophobic stripes on hydrophilic
      surfaces.
AB  - Superhydrophobic patterns were fabricated on hydrophilic surfaces by selective
      painting. The impinging process of water droplets on these hybrid surfaces was
      investigated. The droplet can be split by impinging on the hydrophilic surface
      with a single stripe at a high velocity. The time to split the droplet is
      independent of the impact velocity and it is smaller than the contact time of a
      droplet impinging on the fully superhydrophobic surface. The volume ratios of the
      split mini-droplets could be precisely controlled by adjusting the landing
      position of the original droplet. The droplet could be split uniformly into more
      mini-marbles by increasing the stripe numbers. 

PMID- 25946664
TI  - MRI-based prostate volume-adjusted prostate-specific antigen in the diagnosis of
      prostate cancer.
AB  - PURPOSE: To determine whether prostate-specific antigen (PSA) levels adjusted by
      prostate and zonal volumes estimated from magnetic resonance imaging (MRI)
      improve the diagnosis of prostate cancer (PCa) and differentiation between
      patients who harbor high-Gleason-sum PCa and those without PCa. MATERIALS AND
      METHODS: This retrospective study was Health Insurance Portability and
      Accountability Act (HIPAA)-compliant and approved by the Institutional Review
      Board of participating medical institutions. T2 -weighted MR images were acquired
      for 61 PCa patients and 100 patients with elevated PSA but without PCa. Computer
      methods were used to segment prostate and zonal structures and to estimate the
      total prostate and central-gland (CG) volumes, which were then used to calculate
      CG volume fraction, PSA density, and PSA density adjusted by CG volume. These
      quantities were used to differentiate patients with and without PCa. Area under
      the receiver operating characteristic curve (AUC) was used as the figure of
      merit. RESULTS: The total prostate and CG volumes, CG volume fraction, and PSA
      density adjusted by the total prostate and CG volumes were statistically
      significantly different between patients with PCa and patients without PCa (P <=
      0.007). AUC values for the total prostate and CG volumes, and PSA density
      adjusted by CG volume, were 0.68 +/- 0.04, 0.68 +/- 0.04, and 0.66 +/- 0.04,
      respectively, and were significantly better than that of PSA (P < 0.02), for
      differentiation of PCa patients from patients without PCa. CONCLUSION: The total
      prostate and CG volumes estimated from T2 -weighted MR images and PSA density
      adjusted by these volumes can improve the effectiveness of PSA for the diagnosis
      of PCa and differentiation of high-Gleason-sum PCa patients from patients without
      PCa.

PMID- 25946667
TI  - Comparing the Diagnostic Accuracy of Five Instruments for Detecting Posttraumatic
      Stress Disorder in Youth.
AB  - The purpose of the study was to compare diagnostic accuracy of five posttraumatic
      stress disorder (PTSD) measures in a large outpatient sample of youths 11-18
      years of age. Index tests included a parent report (a rationally derived scale
      from the Child Behavioral Checklist), a teacher report (the Teacher Report Form),
      and three youth reports-a PTSD scale from the Youth Self Report (YSR), Child PTSD
      Symptom Scale, and Child and Adolescent Trauma Survey. Interviews with the youth
      and caregiver using Schedule for Affective Disorders and Schizophrenia for School
      Age Children generated criterion diagnoses of PTSD. Diagnoses were blind to
      scores on the index tests. Based on consensus diagnoses (N = 458), 10% of youth
      had PTSD. Area under the curve (AUC) from receiver operating characteristic
      analyses and multilevel likelihood ratios evaluated test performance. All youth
      reports (AUCs .67-.73) outperformed the teacher report (AUCs .42-.48) at
      identifying PTSD. The YSR outperformed the caregiver reports (AUCs .57-.58).
      Combining tests did not improve prediction of PTSD. The YSR predicted PTSD even
      after controlling for a self-reported traumatic event, but checklist ratings of
      traumatic events had no incremental value after controlling for YSR scores. When
      a youth endorsed few symptoms, the likelihood of the youth having PTSD was low.
      Very high scores on the YSR were associated with a moderate increase in the
      likelihood of PTSD diagnosis. The YSR appeared to be a useful diagnostic aid for
      youth PTSD and could facilitate differential diagnosis of youth PTSD in
      outpatient settings.

PMID- 25946668
TI  - Theranostic Gold Nanomicelles made from Biocompatible Comb-like Polymers for
      Thermochemotherapy and Multifunctional Imaging with Rapid Clearance.
AB  - A new generation of photothermal theranostic agents based on assembling 6 nm gold
      nanoparticles (AuNPs) is developed by using a novel comb-like amphipathic polymer
      as the template. The small AuNPs are assembled into DOX@gold nanomicelles, which
      show strong absorbance in the near-infrared region, for multimodal bioimaging and
      highly effective in vivo chemotherapy and photothermal therapy. 

PMID- 25946669
TI  - Lower-Limb Muscle-Activation Patterns During Off-Axis Elliptical Compared With
      Conventional Gluteal-Muscle-Strengthening Exercises.
AB  - CONTEXT: Gluteal-muscle strength has been identified as an important component of
      injury prevention and rehabilitation in several common knee injuries. However,
      many conventionally prescribed gluteal-strengthening exercises are not performed
      during dynamic weight-bearing activities, which is when most injuries occur.
      OBJECTIVES: To compare lower-limb muscle-activation patterns between conventional
      gluteal-strengthening exercises and off-axis elliptical exercises with motorized
      foot-plate perturbations designed to activate gluteal muscles during dynamic
      exercise. EVIDENCE ACQUISITION: Twelve healthy volunteers (26.1 +/- 4.7 y)
      participated in the study. They performed 3 conventional exercises (single-leg
      squat, forward lunge, and clamshell) and 3 elliptical exercises (regular, while
      resisting an adduction force, and while resisting an internal-rotation torque).
      Gluteus medius (GMed) and maximus (GMax), quadriceps, hamstrings, and
      gastrocnemius muscle activations during each exercise were recorded using surface
      electromyography (EMG) and normalized to maximal voluntary isometric contraction
      (MVIC). EVIDENCE SYNTHESIS: Normalized GMed EMG was the highest during the
      adduction-resistance elliptical exercise (22.4% +/- 14.8% MVIC), significantly
      greater than forward lunge (8.2% +/- 3.8% MVIC) and regular elliptical (6.4% +/-
      2.5% MVIC) and similar to clamshell (19.1% +/- 8.8% MVIC) and single-leg squat
      (18.4% +/- 7.9% MVIC). Normalized GMax EMG during adduction-resistance (11.1% +/-
      7.6% MVIC) and internal-rotation-resistance elliptical (7.4% +/- 3.8% MVIC) was
      significantly greater than regular elliptical (4.4% +/- 2.4% MVIC) and was
      similar to conventional exercises. The single-leg squat required more muscle
      activation from the quadriceps and gastrocnemius than the elliptical exercises.
      CONCLUSIONS: Off-axis elliptical exercise while resisting an adduction force or
      internal-rotation torque activates gluteal muscles dynamically while avoiding
      excessive quadriceps activation during a functional weight-bearing activity
      compared with conventional gluteal-strengthening exercises.

PMID- 25946670
TI  - Exciton delocalization drives rapid singlet fission in nanoparticles of acene
      derivatives.
AB  - We compare the singlet fission dynamics of five pentacene derivatives
      precipitated to form nanoparticles. Two nanoparticle types were distinguished by
      differences in their solid-state order and kinetics of triplet formation.
      Nanoparticles that comprise primarily weakly coupled chromophores lack the bulk
      structural order of the single crystal and exhibit nonexponential triplet
      formation kinetics (Type I), while nanoparticles that comprise primarily more
      strongly coupled chromophores exhibit order resembling that of the bulk crystal
      and triplet formation kinetics associated with the intrinsic singlet fission
      rates (Type II). In the highly ordered nanoparticles, singlet fission occurs most
      rapidly. We relate the molecular packing arrangement derived from the crystal
      structure of the pentacene derivatives to their singlet fission dynamics and find
      that slip stacking leads to rapid, subpicosecond singlet fission. We present
      evidence that exciton delocalization, coincident with an increased relative
      admixture of charge-transfer configurations in the description of the exciton
      wave function, facilitates rapid triplet pair formation in the case of single
      step singlet fission. We extend the study to include two hexacene derivatives and
      find that these conclusions are generally applicable. This work highlights acene
      derivatives as versatile singlet fission chromophores and shows how chemical
      functionalization affects both solid-state order and exciton interactions and how
      these attributes in turn affect the rate of singlet fission. 

PMID- 25946671
TI  - Immunohistochemical assessment of endothelin-1 axis in psoriasis, basal cell
      carcinoma and squamous cell carcinoma.
AB  - AIM: Endothelin-1 is an autocrine growth factor for keratinocytes, an effect
      controlled by its A and B receptors, with no previous comparison of endothelin
      axis expression in inflammatory and neoplastic skin diseases showing keratinocyte
      proliferation. The aim of the study was to investigate endothelin-1 axis
      expression in skin lesions of psoriasis, basal cell carcinoma (BCC), and squamous
      cell carcinoma (SCC). METHODS: This study included 40 subjects (8 patients with
      SCC, 12 patients with BCC, 10 patients with psoriasis, and 10 healthy controls).
      Biopsies from lesional skin of patients and normal skin of controls were examined
      immunohistochemically for endothelin-1 and its receptors A and B frequency and
      grade of expression. RESULTS: Endothelin-1 and receptor A were detected in all
      patients with SCC and psoriasis, with a higher frequency and grade of expression
      than controls and BCC. The frequency of receptor B expression was significantly
      lower while higher staining grade was found in BCC (8.3%) rather than other
      studied groups. CONCLUSION: A comparable higher frequency and grade of expression
      of endothelin-1 and its receptor A are documented in psoriasis and SCC than in
      BCC and controls denoting their involvement in keratinocyte proliferation in both
      diseases. Receptor A is the predominately expressed receptor in psoriasis and
      SCC.

PMID- 25946672
TI  - Clinical efficacy of two topical corticosteroids in the management of chronic
      hand eczema.
AB  - AIM: The aim of this study was to evaluate efficacy, tolerability and safety of a
      combination treatment with fluticasone propionate 0.05% cream and clobetasole
      ointment 0.05% in patients suffering from chronic hand eczema. METHODS: The study
      examined 30 patients with a clinical diagnosis of chronic hand eczema. RESULTS:
      The treatment with topical corticosteroids resulted effective and topical
      corticosteroids proved their efficacy in mild and moderate hand eczema.
      CONCLUSION: In according to the severity of the disease, authors suggest two
      different clinical strategies in the management of hand eczema.

PMID- 25946673
TI  - Efficacy of an emollient dermoprotective cream in the treatment of elderly skin
      affected by xerosis.
AB  - AIM: Xerosis cutis is a frequent condition in the elderly and the topical
      treatments are aimed to maintain a balance between the physiological components
      of the epidermis and an optimal moisturization. The aim was to evaluate the
      efficacy of a dermoprotective cream, glycerol and paraffin-based, in the
      treatment of individuals affected by senile xerosis. METHODS: The patients were
      recruited at the Professional Dermatology and Allergology Outpatient Clinic of
      the San Gallicano Dermatological Institute of Rome, between 1st January 2013 and
      30th September 2014. To assess the efficacy of the cream, two different areas of
      treatment were identified in each patient upper the limbs. All patients were
      staged at baseline (T0) and evaluated after 14 days (T1) and 28 days (T2) of
      topical treatment, using five clinical parameters: scaling, sensation of skin
      tightness, presence of fissuring and excoriations from scratching and erythema.
      The itching degree was also evaluated using a 10-steps analogical scale. RESULTS:
      Fifty patients with xerosis, 25 with a severe and 25 with a moderate form, over
      60 were recruited and evaluated. Median age was 65 years (IQR=61-70). After 28
      day of topical administration of the cream, the 54.0% of patients showed the
      absence of signs of xerosis, the 44.0% a mild form and the 2.0% (one patient) a
      moderate form. Consistently, a progressive and significative reduction of itching
      and transepidermal water loss (TEWL), and an improvement in skin hydration was
      also measured. A good profile of tolerability and no episodes of undesirable side
      effects, was also observed. CONCLUSION: The topical daily use of a cream glycerol
      and paraffin-based, seem to able to control the xerosis in elderly patients, with
      a significant reduction of all associated signs and symptoms. Further additional
      data should be collected to better confirm the role of the topical treatment in
      the control of disease.

PMID- 25946674
TI  - A comprehensive health impact assessment and determinants of quality of life,
      health and psychological status in acne patients.
AB  - AIM: Acne adversely affects all aspects of quality of life (QoL). Although many
      papers assessed acne-specific QoL impairment, there are few data on its impact on
      general health and psychological status. Apart from acne severity, little is
      known about determinants of a worse QoL. The aims of this paper were to measure
      acne impact on QoL, health and psychological status and to analyze the
      relationship between socio-demographic variables, disease severity and mental
      status on QoL of acne sufferers. METHODS: Acne cases were selected from a survey
      conducted in 2010. The Short-Form 12-Item Health Survey and the Skindex-29 were
      used to assess health status and QoL. The 12-Items General Health Questionnaire
      was used to identify individuals at risk for non-psychotic psychiatric disorders
      (GHQ-positive). Physician (PhGA) and patient global assessments were obtained. We
      investigated the variables involved in the QoL through a logistic regression
      analysis. RESULTS: One hundred ninety-five cases were analyzed. Twenty-six
      percent were GHQ-positive; acne's impact on health status was worse compared to
      other chronic diseases. A GHQ-positive status (Skindex-29 overall: OR 2.6; 95% CI
      1.20-5.60, P<0.05, functioning: OR 2.5; 95% CI 1.17-5.44, P<0.05, symptoms: OR
      3.0; 95% CI 1.36-6.53, P<0.01; emotions: OR 2.55; 95% CI 1.19-5.46, P<0.05) and
      having a severe/very severe PhGA (Skindex-29 overall: OR 3.4; 95% CI 1.20-10.38,
      P<0.05) were associated with a poor QoL. Age of onset >25 was linked to being GHQ
      positive (OR 2.92; 95% CI 1.2-7.1, P<0.05) controlling for gender, marital status
      and educational level. CONCLUSION: Acne is not a minor disease in comparison with
      other chronic conditions. Age of onset is capable to influence GHQ status which
      in turn affects QoL.

PMID- 25946675
TI  - Gluten-free diet as a therapeutic approach in psoriatic patients: if yes, when.
AB  - Since most of the studies are mainly confined to cases reporting coincidence of
      psoriasis and celiac disease, the authors want to underline the utility of
      investigating the possible presence of an underlying celiac disease in normal
      practice for a better approach to the patient. It is necessary to carry out
      controlled studies on a large number of patients to evaluate the association
      between these two diseases and the benefits of a gluten-free diet, even when the
      intestinal symptomatology is not evident. 

PMID- 25946676
TI  - Dialysis-associated pseudoporphyria successfully treated with vitamin D. Report
      of two cases.
AB  - Pseudoporphyria refers to a rare bullous dermatosis characterized by the clinical
      and histological features of porfiria cutanea tarda without abnormalities in
      porphyrin metabolism. The pathogenesis is heterogeneous and several exogenous
      factors may promote the bullous lesion formation, including medications, end
      stage renal disease, dialysis and tanning beds. Regarding treatment of this
      condition, in literature different therapy have been reported, such as
      glutathione and his precursor N-acetylcysteine, which presents anti-oxidant
      properties; however even more toxic drugs, such as chloroquine, are used.
      Moreover, in patients with drug-induced PP discontinuation of the offending
      agent, if possible, is a crucial aspect of the clinical management. We report two
      cases of dialysis patients presenting blisters on extremities, which healed with
      the avoidance of UV exposure and oral Vitamin D supplementation. Interestingly
      Vitamin D despite the lack of antioxidant properties led to a completely
      resolution of PP in both our patients within 30 days. A possible explanation of
      this finding is that Vitamin D, playing a key role in the regulation of serum
      Ca2+, can modulated cadherin-cadherin interactions and led to healing of
      pseudoporphyria bullous lesions. Finally we highlight the prominent role of UV
      exposure in PP elicitation thus a good photoprotection is essential for all
      patients with pseudoporphyria. 

PMID- 25946677
TI  - Hutchinson-Gilford progeria.

PMID- 25946678
TI  - Eosinophilic cellulitis.

PMID- 25946679
TI  - Isotretinoin-induced regression of Fordyce spots in a patient with acne: the
      first report.

PMID- 25946680
TI  - Seasonality and survival associated with three outbreak seasons of West Nile
      virus disease in Oklahoma--2003, 2007, and 2012.
AB  - West Nile virus (WNV) activity has fluctuated in the south-central United States
      since its introduction. Seasonal outbreaks are common, with three in Oklahoma
      during 2003, 2007, and 2012. Morbidity and mortality rates vary during each
      outbreak. Long-term neurologic sequelae in association with West Nile virus
      disease (WNVD) are well-described, but limited information is available about
      delayed mortality among acute WNV infection survivors. A retrospective cohort
      analysis of all confirmed and probable WNVD cases reported to the Oklahoma State
      Department of Health (OSDH) during 2003, 2007, and 2012 was performed. OSDH
      surveillance data and mortality data from Oklahoma's vital statistics database
      were used to construct a descriptive epidemiologic analysis of the geography,
      temporality, severity, and associated mortality for each outbreak season. A
      Kaplan-Meier survival curve and standardized mortality ratios (SMRs) were
      calculated to measure survival of the 2003 and 2007 WNVD cohorts. Seventy-nine
      cases during 2003, 107 cases during 2007, and 180 cases during 2012 met inclusion
      criteria. Median ages of the 2003, 2007, and 2012 cohorts were 48, 58, and 59
      years, respectively; race, sex, and symptom information were not substantially
      different. Each outbreak season had a different severity, temporality, and
      geography. Age- and sex-adjusted SMRs for the combined 2003 and 2007 cohorts
      censored at 5 years was 0.9 (95% confidence interval 0.51-1.75); no substantial
      difference was observed between the survival curves. Although similar patterns of
      long-term mortality were evident on the survival curves, SMRs did not demonstrate
      increased 5-year cumulative risk for death for patients surviving acute WNV
      infection.

PMID- 25946681
TI  - Negative affect, interpersonal perception, and binge eating behavior: An
      experience sampling study.
AB  - OBJECTIVE: Etiological and maintenance models for disordered eating highlight the
      salience of negative affect and interpersonal dysfunction. This study employed a
      14-day experience sampling procedure to assess the impact of negative affect and
      interpersonal perceptions on binge eating behavior. METHOD: Young adult women (N
      = 40) with recurrent binge eating and significant clinical impairment recorded
      their mood, interpersonal behavior, and eating behaviors at six stratified
      semirandom intervals daily through the use of personal digital assistants.
      RESULTS: Although momentary negative affect was associated with binge eating
      behavior, average levels of negative affect over the experience sampling period
      were not, and interpersonal problems moderated the relationship between negative
      affect and binge eating. Interpersonal problems also intensified the association
      between momentary interpersonal perceptions and binge eating behavior. Lagged
      analyses indicated that previous levels of negative affect and interpersonal
      style also influence binge eating. DISCUSSION: The study findings suggest there
      may be important differences in how dispositional versus momentary experiences of
      negative affect are associated with binge eating. Results also highlight the
      importance of interpersonal problems for understanding relationships among
      negative affect, interpersonal perception, and binge eating behavior. These
      results offer several possibilities for attending to affective and interpersonal
      functioning in clinical practice.

PMID- 25946683
TI  - Evaluation of a new mid-scala cochlear implant electrode using microcomputed
      tomography.
AB  - OBJECTIVES/HYPOTHESIS: To investigate electrode position, depth of insertion, and
      electrode contact using an electrode array with a mid-scala design following
      round window (RW) and cochleostomy insertion. STUDY DESIGN: Eight fresh-frozen
      cadaveric bones were implanted; half via a RW approach and half through an
      anteroinferior cochleostomy using a styleted mid-scala electrode design. METHODS:
      Microcomputed tomography was used to acquire oblique coronal and oblique axial
      reformations. Individual electrode positions along each array, insertional depth,
      and electrode contact were determined using National Institutes of Health Image J
      software. RESULTS: All electrodes were inserted without significant resistance.
      The average angular depth of insertion was 436.5 degrees  for the RW group and
      422.7 degrees  for the cochleostomy group. All electrodes acquired a perimodiolar
      position in the proximal segment and a lateral wall position at the basal turn,
      regardless of approach. Electrodes distal to the basal turn demonstrated a
      variable location, with 78% mid scala. One cochleostomy array fractured through
      the interscalar partition (ISP), acquiring a scala vestibuli position. The odds
      ratio for either abutting the modiolus, ISP, lateral wall or floor, or fracturing
      through the ISP were 2.7 times more likely following a cochleostomy insertion (P
      = .032). CONCLUSIONS: The styleted mid-scala electrode design acquires a proximal
      perimodiolar position, a lateral wall location, as it traverses the basal turn,
      and most commonly a mid-scala position in the distal array. Interscalar excursion
      occurred in one of the cochleostomy insertions. Cochleostomy insertion is more
      likely to result in ultimate final electrode position adjacent to critical
      intracochlear structures. LEVEL OF EVIDENCE: NA.

PMID- 25946684
TI  - Intramolecular oxidative coupling: I2/TBHP/NaN3-mediated synthesis of benzofuran
      derivatives.
AB  - A novel intramolecular oxidative coupling reaction has been established to
      prepare benzofuran derivatives via direct C(sp(2))-H functionalization for the
      formation of C-O bond. This transformation is mediated by I2/TBHP/NaN3 under
      metal-free conditions and a catalytic amount of NaN3 plays a crucial role in the
      reaction. Furthermore, the reaction tolerates a broad substrate scope with
      average to excellent yields. 

PMID- 25946682
TI  - Apcdd1 stimulates oligodendrocyte differentiation after white matter injury.
AB  - Wnt signaling plays an essential role in developmental and regenerative
      myelination of the CNS, therefore it is critical to understand how the factors
      associated with the various regulatory layers of this complex pathway contribute
      to these processes. Recently, Apcdd1 was identified as a negative regulator of
      proximal Wnt signaling, however its role in oligodendrocyte (OL) differentiation
      and reymelination in the CNS remain undefined. Analysis of Apcdd1 expression
      revealed dynamic expression during OL development, where its expression is
      upregulated during differentiation. Functional studies using ex vivo and in vitro
      OL systems revealed that Apcdd1 promotes OL differentiation, suppresses Wnt
      signaling, and associates with beta-catenin. Application of these findings to
      white matter injury (WMI) models revealed that Apcdd1 similarly promotes OL
      differentiation after gliotoxic injury in vivo and acute hypoxia ex vivo.
      Examination of Apcdd1 expression in white matter lesions from neonatal WMI and
      adult multiple sclerosis revealed its expression in subsets of oligodendrocyte
      (OL) precursors. These studies describe, for the first time, the role of Apcdd1
      in OLs after WMI and reveal that negative regulators of the proximal Wnt pathway
      can influence regenerative myelination, suggesting a new therapeutic strategy for
      modulating Wnt signaling and stimulating repair after WMI.

PMID- 25946685
TI  - Long-term stability, reproducibility, and statistical sensitivity of a telemetry
      instrumented dog model: A 27-month longitudinal assessment.
AB  - INTRODUCTION: ICH guidelines, as well as best-practice and ethical
      considerations, provide strong rationale for use of telemetry-instrumented dog
      colonies for cardiovascular safety assessment. However, few studies have
      investigated the long-term stability of cardiovascular function at baseline,
      reproducibility in response to pharmacologic challenge, and maintenance of
      statistical sensitivity to define the usable life of the colony. These questions
      were addressed in 3 identical studies spanning 27months and were performed in the
      same colony of dogs. METHODS: Telemetry-instrumented dogs (n=4) received a single
      dose of dl-sotalol (10mg/kg, p.o.), a beta1 adrenergic and IKr blocker, or
      vehicle, in 3 separate studies spanning 27months. Systemic hemodynamics,
      cardiovascular function, and ECG parameters were monitored for 18h post-dose;
      plasma drug concentrations (Cp) were measured at 1, 3, 5, and 24h post-dose.
      RESULTS: Baseline hemodynamic/ECG values were consistent across the 27-month
      study with the exception of modest age-dependent decreases in heart rate and the
      corresponding QT-interval. dl-Sotalol elicited highly reproducible effects in
      each study. Reductions in heart rate after dl-sotalol treatment ranged between 
      22 and -32 beats/min, and slight differences in magnitude could be ascribed to
      variability in dl-sotalol Cp (range=3230-5087ng/mL); dl-sotalol also reduced LV
      dP/dtmax 13-22%. dl-Sotalol increased the slope of the PR-RR relationship
      suggesting inhibition of AV-conduction. Increases in the heart-rate corrected QT
      interval were not significantly different across the 3 studies and results of a
      power analysis demonstrated that the detection limit for QTc values was not
      diminished throughout the 27month period and across a range of power assumptions
      despite modest, age-dependent changes in heart rate. DISCUSSION: These results
      demonstrate the long-term stability of a telemetry dog colony as evidenced by a
      stability of baseline values, consistently reproducible response to pharmacologic
      challenge and no diminished statistical sensitivity over time.

PMID- 25946686
TI  - Risk stratification in 3-vessel coronary artery disease: Applying the SYNTAX
      Score II in the Heart Team Discussion of the SYNTAX II trial.
AB  - BACKGROUND: Heart Team (HT) and the SYNTAX Score II (SSII) have been integrated
      to the contemporary guidelines with the aim to provide a multidisciplinary
      decision-making process between coronary artery bypass surgery (CABG) and
      percutaneous coronary intervention (PCI). AIMS: To prospectively assess the
      agreement between the HT decision and the SSII recommendation regarding the
      revascularization strategy in patients with 3-vessel coronary artery disease
      (CAD) of the SYNTAX II trial. METHODS: The SSII predicts the 4-year mortality of
      an individual patient both after PCI and after CABG. Patients were treated by PCI
      when the SSII predicted a mortality risk favoring PCI or when risk predictions
      were equipoise between PCI and CABG. However, the HT could overrule the SSII and
      recommend either CABG or PCI. RESULTS: A total of 202 patients have been screened
      and 24 did not fulfill inclusion criteria. The median age was 67.0 (IQR 59.0
      73.3), and 167 (82.7%) were male. The HT endorsed SSII treatment recommendation,
      for CABG or PCI, in 152 patients (85.4%). Three patients had preference for PCI,
      irrespective of the HT decision. The main reason for the HT to overrule the SSII
      and recommend CABG was the prospect of a more complete revascularization (21 of
      25 patients). Patients recommended for CABG by the HT had significantly higher
      anatomical SYNTAX score (P = 0.03) and higher predicted mortality risk for PCI (P
      = 0.04) when compared with patients that were enrolled in the trial. CONCLUSION:
      The SYNTAX score II showed to be a suitable tool for guiding treatment decisions
      of patients with 3-vessel coronary artery disease being endorsed by the HT in the
      vast majority of the patients that have been enrolled in the SYNTAX II trial.

PMID- 25946688
TI  - ASYMMETRY IN MACULAR CHOROIDAL THICKNESS PROFILE BETWEEN BOTH EYES IN A HEALTHY
      POPULATION MEASURED BY SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY.
AB  - PURPOSE: To determine the difference in macular choroidal thickness (CT) profile
      between eyes in healthy individuals using swept-source optical coherence
      tomography. DESIGN: Cross-sectional noninterventional study. PARTICIPANTS: One
      hundred and forty eyes from 70 healthy patients with spherical equivalent between
      +/- 3 D and with difference <= 0.25 D between eyes were scanned using a swept
      source optical coherence tomography (Topcon Corporation). METHODS: Cross
      sectional noninterventional study. One hundred and forty eyes from 70 healthy
      patients with spherical equivalent between +/- 3 D and with difference #0.25 D
      between eyes were scanned using a swept-source optical coherence tomography
      (Topcon Corporation). A horizontal CT profile of the macula was created in both
      eyes by manually measuring the subfoveal CT from the posterior edge of retinal
      pigment epithelium (RPE) to the choroid/sclera junction. Three determinations
      were performed at successive points 1,000 mm nasal to the fovea and 5 more
      temporal to the fovea. The differences in CT between both eyes were analyzed.
      RESULTS: Mean age was 25.4 +/- 19.9 years (from 4 to 75). The mean spherical
      equivalent was 0.18 +/- 1.37 D (from -3 to +3). Mean macular nasal CT was thicker
      in the right eye (RE) than in the left eye (LE) (228.11 +/- 69.23 MUm vs. 212.27
      +/- 62.71 MUm; P = 0.0002; Student's t-test paired data). Mean subfoveal CT and
      mean temporal CT was not statistically significantly different between the eyes.
      No statistically significant differences were observed comparing spherical
      equivalent in the RE compared with the LE. Both men and women showed a thicker
      mean nasal choroid in the RE versus the left (men, 226.97 +/- 61.56 MUm vs.
      209.87 +/- 60.31 MUm; women, 229.63 +/- 79.39 MUm vs. 215.47 +/- 66.68 MUm, P =
      0.003 and P = 0.03, respectively; Student's t-test paired data). At each nasal
      determination, CT in the RE was statistically significantly thicker than the LE
      (N1: 283.72 +/- 81.10 MUm vs. 269.76 +/- 75.81 MUm [P = 0.001]; in N2: 230.45 +/-
      73.47 MUm vs. 211.33 +/- 66.92 MUm [P = 0.0002]; and in N3: 170.16 +/- 61.00 MUm
      vs. 155.72 +/- 53.87 MUm [P = 0.008], respectively). CONCLUSION: To the best of
      our knowledge, this is the first report suggesting thicker macular nasal choroid
      in the RE compared with the LE. In contrast, subfoveal CT and temporal CT were
      not found to be different between eyes.

PMID- 25946687
TI  - High-density lipoprotein inhibits mechanical stress-induced cardiomyocyte
      autophagy and cardiac hypertrophy through angiotensin II type 1 receptor-mediated
      PI3K/Akt pathway.
AB  - Mechanical stress triggers cardiac hypertrophy and autophagy through an
      angiotensin II (Ang II) type 1 (AT1) receptor-dependent mechanism. Low level of
      high density lipoprotein (HDL) is an independent risk factor for cardiac
      hypertrophy. This study was designed to evaluate the effect of HDL on mechanical
      stress-induced cardiac hypertrophy and autophagy. A 48-hr mechanical stretch and
      a 4-week transverse aortic constriction were employed to induce cardiomyocyte
      hypertrophy in vitro and in vivo, respectively, prior to the assessment of
      myocardial autophagy using LC3b-II and beclin-1. Our results indicated that HDL
      significantly reduced mechanical stretch-induced rise in autophagy as
      demonstrated by LC3b-II and beclin-1. In addition, mechanical stress up-regulated
      AT1 receptor expression in both cultured cardiomyocytes and in mouse hearts,
      whereas HDL significantly suppressed the AT1 receptor. Furthermore, the role of
      Akt phosphorylation in HDL-mediated action was assessed using MK-2206, a
      selective inhibitor for Akt phosphorylation. Our data further revealed that MK
      2206 mitigated HDL-induced beneficial responses on cardiac remodelling and
      autophagy. Taken together, our data revealed that HDL inhibited mechanical stress
      induced cardiac hypertrophy and autophagy through downregulation of AT1 receptor,
      and HDL ameliorated cardiac hypertrophy and autophagy via Akt-dependent
      mechanism. 

PMID- 25946689
TI  - LONG-TERM OUTCOMES OF 23-GAUGE PARS PLANA VITRECTOMY WITH INTERNAL LIMITING
      MEMBRANE PEELING AND GAS TAMPONADE FOR MYOPIC TRACTION MACULOPATHY: A Prospective
      Study.
AB  - PURPOSE: To investigate the long-term safety and efficacy of microincisional 23
      gauge pars plana vitrectomy with internal limiting membrane (ILM) peeling and gas
      tamponade in the treatment of myopic traction maculopathy. METHODS: A prospective
      nonrandomized multicenter study was designed. Patients with myopic traction
      maculopathy without macular hole and retinal detachment were included in the
      study between January 2009 and May 2012. All patients underwent microincisional
      23-gauge pars plana vitrectomy with ILM peeling and 12% C3F8 gas tamponade. In
      all cases, brilliant blue G staining of the ILM was performed. All patients were
      prospectively evaluated. The evolution of best-corrected visual acuity (BCVA) and
      macular thickness were recorded. RESULTS: Myopic traction maculopathy resolved in
      28 of the 30 patients (93%) included. Mean follow-up was 33.8 +/- 13 months
      (range, 24-60 months). Mean time of myopic traction maculopathy resolution after
      surgery was 2.65 +/- 1.4 months. At 1 month after surgery, one patient developed
      a macular hole and another one a rhegmatogenous retinal detachment. After 2
      years, another patient developed a retinal detachment. Statistically significant
      improvements in macular thickness compared with baseline were found at all follow
      up visits (P < 0.001, Student's t-test). At final visit, BCVA improved
      significantly compared with baseline (P = 0.044, Wilcoxon's test). However, a
      statistically significant improvement in visual acuity was achieved only in eyes
      with a preoperative Snellen visual acuity >= 20/63 (P = 0.027). In contrast, the
      final BCVA of eyes with worse preoperative visual acuity (<20/63) did not improve
      significantly (P = 0.41, Wilcoxon's test). CONCLUSION: Microincisional 23-gauge
      pars plana vitrectomy with ILM peeling and gas tamponade is effective in the
      treatment of myopic traction maculopathy, with low postoperative complications.
      Globally, both BCVA and macular thickness improved significantly during the
      follow-up period. However, greater visual acuity improvements were only seen in
      eyes with preoperative BCVA equal to or better than 20/63 Snellen equivalent.
      Some concerns remain about the risk of macular hole formation after ILM peeling.
      Further studies are necessary to investigate this issue.

PMID- 25946690
TI  - Vitrectomy using 0.025% povidone-iodine in balanced salt solution plus for the
      treatment of postoperative endophthalmitis.
AB  - PURPOSE: To investigate the bactericidal effect of 0.025% povidone-iodine in
      Balanced Salt Solution PLUS (0.025% PI-BSS PLUS) and its use in vitrectomy for
      postoperative endophthalmitis. METHODS: First, an experimental laboratory model
      using Staphylococcus aureus was used to evaluate the bactericidal effect of PI
      BSS PLUS. Next, in a case series of 4 eyes with postoperative endophthalmitis,
      vitrectomy using 0.025% PI-BSS PLUS as irrigation solution was conducted,
      followed by postoperative intravitreal and intravenous antibiotics. RESULTS: In
      in vitro study, PI at concentrations of 0.01% and above in BSS PLUS exhibited
      marked bactericidal effect after 15 seconds of exposure. Bactericidal effect of
      0.025% PI-BSS PLUS was maintained at room temperature storage for 15 minutes but
      was attenuated after 30 minutes. Among 4 eyes that underwent vitrectomy using
      0.025% PI-BSS PLUS, coagulase-negative Staphylococcus sp. was isolated in 1 eye
      at the beginning but not at completion of surgery. In all four eyes,
      endophthalmitis was resolved with no adverse events. Ocular toxicity was not
      observed. CONCLUSION: The 0.025% PI-BSS PLUS is bactericidal and nontoxic when
      used as irrigation solution in vitrectomy. In 4 cases of postoperative
      endophthalmitis, vitrectomy using 0.025% PI-BSS PLUS followed by postoperative
      antibiotics resolved endophthalmitis.

PMID- 25946691
TI  - TEMPORAL INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE VERSUS CLASSIC
      INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE: A Comparative Study.
AB  - PURPOSE: To determine if reducing the area of internal limiting membrane (ILM)
      peeling in the inverted ILM flap technique results in satisfactory outcomes for
      the repair of large Stage IV idiopathic macular holes. METHODS: Prospective
      comparative interventional study of 87 consecutive eyes. Participants were
      randomized into two treatment groups. In Group A, the classic inverted ILM flap
      technique was performed. In Group B, a modification of this procedure, the
      temporal inverted ILM flap technique, was performed. In the modified inverted ILM
      flap technique, peeling of the ILM was restricted to the temporal side of the
      fovea only--the macular hole was then covered with the temporal ILM flap.
      RESULTS: There was no significant difference in initial and final visual acuities
      between Groups A and B. In both groups, defects in photoreceptors and the
      external limiting membrane decreased with time. Successive postoperative
      examinations revealed an increasing number of patients with the dissociated optic
      nerve fiber layer appearance, although this was less frequent in Group B
      (modified ILM flap) than in Group A. CONCLUSION: The study results indicate that
      the temporal inverted ILM flap technique is as effective as the classic inverted
      ILM flap technique for the repair of large Stage IV macular holes.

PMID- 25946692
TI  - ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR NEOVASCULAR AGE-RELATED
      MACULAR DEGENERATION: Outcomes in Eyes With Poor Initial Vision.
AB  - PURPOSE: To assess the effect of anti-vascular endothelial growth factor
      treatment on visual acuity outcome in patients with neovascular age-related
      macular degeneration presenting with very low vision. METHODS: Retrospective
      analysis of electronic patient care record of 420 eyes treated with ranibizumab
      between March 2010 and June 2013. The authors classified the extracted sample
      into 3 categories based on the initial best-corrected visual acuity (BCVA) as
      measured on the Early Treatment Diabetic Retinopathy Study charts: 0 to 35
      letters, 36 to 69 letters, and >= 70 letters. Best BCVA achieved in Year 1, and
      average BCVA over 36 months was computed. The neovascular lesion type, area of
      lesion, the presence or absence of hemorrhage, retinal pigment epithelium tear,
      and atrophy were systematically graded as was extent of fibrosis on a categorical
      scale of 0 to 4. Regression analysis was performed with the best BCVA achieved in
      Year 1 as the outcome variable and initial BCVA, person, and lesion
      characteristics as explanatory variables. RESULTS: The mean change in BCVA from
      the initial visit to the best-attained BCVA during Year 1 was highly
      statistically significant with an improvement of 9.95 letters. The improvement
      from initial BCVA to average BCVA over 36 months was 4.01 letters. Regression
      analysis identified atrophy and fibrosis as predictors of best BCVA, with the
      model having an r of 0.71. CONCLUSION: Our study supports the use of anti
      vascular endothelial growth factor agents even in eyes with low visual acuity
      particularly when fibrosis and atrophy are absent and suggests algorithms to
      predict outcome for combinations of visual acuity and lesion characteristics
      across the full visual acuity range.

PMID- 25946693
TI  - SUBFOVEAL CHOROIDAL THICKNESS CHANGES IN TREATED IDIOPATHIC CENTRAL SEROUS
      CHORIORETINOPATHY AND THEIR ASSOCIATION WITH RECURRENCE.
AB  - PURPOSE: To analyze the changes in subfoveal choroidal thickness (SFChT) before
      and after resolution of central serous chorioretinopathy (CSC) and their
      association with recurrence during follow-up. METHODS: Seventy-six eyes with CSC
      that were completely resolved after treatment with either intravitreal
      bevacizumab (IVB, 42 eyes) or with half-fluence photodynamic therapy (34 eyes)
      were included. Best-corrected visual acuity and spectral domain optical coherence
      tomography were performed at baseline, after complete resolution, and at regular
      intervals thereafter. RESULTS: Subfoveal choroidal thickness was similar in the
      IVB-treated and half-fluence photodynamic therapy-treated eyes at baseline, as
      well as after complete resolution of the CSC. However, recurrence was more
      frequent in the IVB-treated eyes (19.0% vs. 2.9%, P = 0.037). The reduction of
      SFChT after CSC resolution was greater in the nonrecurrent eyes than in the
      recurrent eyes (91.35 +/- 46.40 vs. 19.25 +/- 16.47 MUm, P < 0.001), and the
      extent of SFChT reduction was associated with the rate of recurrence of CSC (odds
      ratio = 0.877, P = 0.019). When CSC recurred, SFChT increased toward the baseline
      value. CONCLUSION: Treatment of idiopathic CSC by both IVB and half-fluence
      photodynamic therapy can reduce SFChT when subretinal fluid is completely
      resolved. Recurrence is more frequent after IVB and specifically in eyes with a
      smaller reduction in SFChT after resolution of the CSC.

PMID- 25946694
TI  - Twenty-seven-gauge vitrectomy for various vitreoretinal diseases.

PMID- 25946695
TI  - Correspondence.

PMID- 25946696
TI  - Reply: To PMID 24732699.

PMID- 25946698
TI  - Business as usual is not acceptable.

PMID- 25946697
TI  - Tailoring material properties of cardiac matrix hydrogels to induce endothelial
      differentiation of human mesenchymal stem cells.
AB  - Cardiac matrix hydrogel has shown great promise as an injectable biomaterial due
      to the possession of cardiac-specific extracellular matrix composition. A cardiac
      matrix hydrogel facilitating neovascularization will further improve its
      therapeutic outcomes in cardiac repair. In this study, we explored the
      feasibility of tailoring material properties of cardiac matrix hydrogels using a
      natural compound, genipin, to promote endothelial differentiation of stem cells.
      Our results demonstrated that the genipin cross-linking could increase the
      mechanical properties of the cardiac matrix hydrogel to a stiffness range
      promoting endothelial differentiation of human mesenchymal stem cells (hMSCs). It
      also decreased the swelling ratio and prolonged degradation without altering
      gelation time. Human mesenchymal stem cells cultured on the genipin cross-linked
      cardiac matrix hydrogels showed great viability. After 1 day culture, hMSCs
      demonstrated down-regulation of early endothelial marker expression and up
      regulation of mature endothelial marker expression. Especially for 1 mM genipin
      cross-linked cardiac matrix hydrogels, hMSCs showed particularly significant
      expression of mature endothelial cell marker vWF. These attractive results
      indicate the potential of using genipin cross-linked cardiac matrix hydrogels to
      promote rapid vascularization for cardiac infarction treatment through minimally
      invasive therapy. 

PMID- 25946699
TI  - Historical classics: Oldies but goodies.

PMID- 25946700
TI  - Assessing Capacity for Sustainability of Effective Programs and Policies in Local
      Health Departments.
AB  - CONTEXT: Sustainability has been defined as the existence of structures and
      processes that allow a program to leverage resources to effectively implement and
      maintain evidence-based public health and is important in local health
      departments (LHDs) to retain the benefits of effective programs. OBJECTIVE:
      Explore the applicability of the Program Sustainability Framework in high- and
      low-capacity LHDs as defined by national performance standards. DESIGN: Case
      study interviews from June to July 2013. Standard qualitative methodology was
      used to code transcripts; codes were developed inductively and deductively.
      SETTING: Six geographically diverse LHD's (selected from 3 of high and 3 of low
      capacity) PARTICIPANTS: : 35 LHD practitioners. MAIN OUTCOME MEASURES: Thematic
      reports explored the 8 domains (Organizational Capacity, Program Adaptation,
      Program Evaluation, Communications, Strategic Planning, Funding Stability,
      Environmental Support, and Partnerships) of the Program Sustainability Framework.
      RESULTS: High-capacity LHDs described having environmental support, while low
      capacity LHDs reported this was lacking. Both high- and low-capacity LHDs
      described limited funding; however, high-capacity LHDs reported greater funding
      flexibility. Partnerships were important to high- and low-capacity LHDs, and both
      described building partnerships to sustain programming. Regarding organizational
      capacity, high-capacity LHDs reported better access to and support for adequate
      staff and staff training when compared with low-capacity LHDs. While high
      capacity LHDs described integration of program evaluation into implementation and
      sustainability, low-capacity LHDs reported limited capacity for measurement
      specifically and evaluation generally. When high-capacity LHDs described program
      adoption, they discussed an opportunity to adapt and evaluate. Low-capacity LHDs
      struggled with programs requiring adaptation. High-capacity LHDs described higher
      quality communication than low-capacity LHDs. High- and low-capacity LHDs
      described strategic planning, but high-capacity LHDs reported efforts to
      integrate evidence-based public health. CONCLUSIONS: Investments in leadership
      support for improving organizational capacity, improvements in communication from
      the top of the organization, integrating program evaluation into implementation,
      and greater funding flexibility may enhance sustainability of evidence-based
      public health in LHDs.

PMID- 25946701
TI  - Trends in Disparity by Sex and Race/Ethnicity for the Leading Causes of Death in
      the United States-1999-2010.
AB  - CONTEXT: Temporal trends in disparities in the leading causes of death within and
      between US demographic subgroups indicate the need for and success of
      interventions to prevent premature death in vulnerable populations. Studies that
      report recent trends are limited and outdated. OBJECTIVE: To describe temporal
      trends in disparities in death rates by sex and race/ethnicity for the 10 leading
      causes of death in the United States during 1999-2010. DESIGN: We used underlying
      cause of death data and population estimates from the National Vital Statistics
      System to calculate age-adjusted death rates for the 10 leading causes of death
      during 1999-2010. We measured absolute and relative disparities by sex and
      race/ethnicity for each cause and year of death; we used weighted linear
      regression to test for significance of trends over time. RESULTS: Of the 10
      leading causes of death, age-adjusted death rates by sex and race/ethnicity
      declined during 1999-2010 for 6 causes and increased for 4 causes. But sex and
      racial/ethnic disparities between groups persisted for each year and cause of
      death. In the US population, the decreasing trend during 1999-2010 was greatest
      for cerebrovascular disease (-36.5%) and the increasing trend was greatest for
      Alzheimer disease (52.4%). For each sex and year, the disparity in death rates
      between Asian/Pacific Islanders (API) and other groups varied significantly by
      cause of death. In 2010, the API-non-Hispanic black disparity was largest for
      heart disease, malignant neoplasms, cerebrovascular diseases, and nephritis; the
      API-American Indian/Alaska Native disparity was largest for unintentional injury,
      diabetes mellitus, influenza and pneumonia, and suicide; and the API-non-Hispanic
      white disparity was largest for chronic lower respiratory diseases and Alzheimer
      disease. CONCLUSIONS: Public health practitioners can use these findings to
      improve policies and practices and to evaluate progress in eliminating
      disparities and their social determinants in vulnerable populations.

PMID- 25946702
TI  - Epistasis Is a Major Determinant of the Additive Genetic Variance in Mimulus
      guttatus.
AB  - The influence of genetic interactions (epistasis) on the genetic variance of
      quantitative traits is a major unresolved problem relevant to medical,
      agricultural, and evolutionary genetics. The additive genetic component is
      typically a high proportion of the total genetic variance in quantitative traits,
      despite that underlying genes must interact to determine phenotype. This study
      estimates direct and interaction effects for 11 pairs of Quantitative Trait Loci
      (QTLs) affecting floral traits within a single population of Mimulus guttatus.
      With estimates of all 9 genotypes for each QTL pair, we are able to map from QTL
      effects to variance components as a function of population allele frequencies,
      and thus predict changes in variance components as allele frequencies change.
      This mapping requires an analytical framework that properly accounts for bias
      introduced by estimation errors. We find that even with abundant interactions
      between QTLs, most of the genetic variance is likely to be additive. However, the
      strong dependency of allelic average effects on genetic background implies that
      epistasis is a major determinant of the additive genetic variance, and thus, the
      population's ability to respond to selection. 

PMID- 25946703
TI  - Free-breathing liver perfusion imaging using 3-dimensional through-time spiral
      generalized autocalibrating partially parallel acquisition acceleration.
AB  - OBJECTIVES: The goal of this study was to develop free-breathing high
      spatiotemporal resolution dynamic contrast-enhanced liver magnetic resonance
      imaging using non-Cartesian parallel imaging acceleration, and quantitative liver
      perfusion mapping. MATERIALS AND METHODS: This study was approved by the local
      institutional review board and written informed consent was obtained from all
      participants. Ten healthy subjects and 5 patients were scanned on a Siemens 3-T
      Skyra scanner. A stack-of-spirals trajectory was undersampled in-plane with a
      reduction factor of 6 and reconstructed using 3-dimensional (3D) through-time non
      Cartesian generalized autocalibrating partially parallel acquisition. High
      resolution 3D images were acquired with a true temporal resolution of 1.6 to 1.9
      seconds while the subjects were breathing freely. A dual-input single-compartment
      model was used to retrieve liver perfusion parameters from dynamic contrast
      enhanced magnetic resonance imaging data, which were coregistered using an
      algorithm designed to reduce the effects of dynamic contrast changes on
      registration. Image quality evaluation was performed on spiral images and
      conventional images from 5 healthy subjects. RESULTS: Images with a spatial
      resolution of 1.9 * 1.9 * 3 mm3 were obtained with whole-liver coverage. With an
      imaging speed of better than 2 s/vol, free-breathing scans were achieved and
      dynamic changes in enhancement were captured. The overall image quality of free
      breathing spiral images was slightly lower than that of conventional long breath
      hold Cartesian images, but it provided clinically acceptable or better image
      quality. The free-breathing 3D images were registered with almost no residual
      motion in liver tissue. After the registration, quantitative whole-liver 3D
      perfusion maps were obtained and the perfusion parameters are all in good
      agreement with the literature. CONCLUSIONS: This high-spatiotemporal resolution
      free-breathing 3D liver imaging technique allows voxelwise quantification of
      liver perfusion.

PMID- 25946704
TI  - Illness perceptions within 6 months of cancer diagnosis are an independent
      prospective predictor of health-related quality of life 15 months post-diagnosis.
AB  - OBJECTIVE: Studies have found that illness perceptions explain significant
      variance in health outcomes in numerous diseases. However, most of the research
      is cross-sectional and non-oncological. We examined, for the first time in
      breast, colorectal and prostate cancer patients, if cognitive and emotional
      illness perceptions near diagnosis predict future multidimensional health-related
      quality of life (HRQoL). METHODS: UK-based patients (N = 334) completed the
      illness perception questionnaire-revised within 6 months post-diagnosis and the
      quality of life in adult cancer survivors scale 15 months post-diagnosis.
      Sociodemographic and clinical data were obtained from medical records.
      Hierarchical multiple regression analyses were conducted. RESULTS: The
      sociodemographic and clinical factors collectively significantly predicted 8/12
      HRQoL domains, although for 5/8 accounted for <10% of the variance. For all 12
      HRQoL domains, illness perceptions collectively explained significant substantial
      additional variance (?R(2) range: 5.6-27.9%), and a single illness perception
      questionnaire-revised dimension was the best individual predictor of 9/12 HRQoL
      domains. The consequences dimension independently predicted 7/12 HRQoL domains;
      patients who believed their cancer would have a more serious negative impact on
      their life reported poorer future HRQoL. The emotional representations and
      identity dimensions also predicted multiple HRQoL domains. CONCLUSIONS: Future
      research should focus on realising the potential of illness perceptions as a
      modifiable target for and mediating mechanism of interventions to improve
      patients' HRQoL.

PMID- 25946705
TI  - The ADOR mechanism for the synthesis of new zeolites.
AB  - A novel methodology, called ADOR (assembly-disassembly-organisation-reassembly),
      for the synthesis of zeolites is reviewed here in detail. The ADOR mechanism
      stems from the fact that certain chemical weakness against a stimulus may be
      present in a zeolite framework, which can then be utilized for the preparation of
      new solids through successive manipulation of the material. In this review, we
      discuss the critical factors of germanosilicate zeolites required for application
      of the ADOR protocol and describe the mechanism of hydrolysis, organisation and
      condensation to form new zeolites starting from zeolite UTL. Last but not least,
      we discuss the potential of this methodology to form other zeolites and the
      prospects for future investigations. 

PMID- 25946706
TI  - IgG abzymes with peroxidase and oxidoreductase activities from the sera of
      healthy humans.
AB  - We present the evidence showing that small fractions of electrophoretically
      homogeneous immunoglobulin G (IgGs) from the sera of healthy humans and their Fab
      and F(ab)2 fragments oxidize 3,3'-diaminobenzidine through a peroxidase activity
      in the presence of H2 O2 and through an oxidoreductase activity in the absence of
      H2 O2 . During purification on protein G-Sepharose and gel filtration, the
      polyclonal IgGs partially lose the Me(2+) ions. After extensive dialysis of
      purified Abs against agents chelating metal ions, the relative peroxidase
      activity decreased dependently of IgG analyzed from 100 to ~10-85%, while
      oxidoreductase activity from 100 to 14-83%. Addition of external metal ions to
      dialyzed and non-dialyzed IgGs leads to a significant increase in their activity.
      Chromatography of the IgGs on Chelex non-charged with Cu(2+) ions results in the
      adsorption of a small IgG fraction bound with metal ions (~5%), while Chelex
      charged with Cu(2+) ions bind additionally ~38% of the total IgGs. Separation of
      Abs on both sorbents results in IgG separation to many different subfractions
      demonstrating various affinities to the chelating resin and different levels of
      the specific oxidoreductase and peroxidase activities. In the presence of
      external Cu(2+) ions, the specific peroxidase activity of several IgG
      subfractions achieves 20-27 % as compared with horseradish peroxidase (HRP, taken
      for 100%). The oxidoreductase activity of these fractions is ~4-6-fold higher
      than that for HRP. Antioxidant enzymes such as superoxide dismutases, catalases,
      and glutathione peroxidases are known to represent critical defence mechanisms
      for preventing oxidative modifications of DNA, proteins, and lipids. Peroxidase
      and oxidoreductase activities of human IgGs could also play an important role in
      the protection of organisms from oxidative stress and toxic compounds.

PMID- 25946707
TI  - Can a Single-Leg Squat Provide Insight Into Movement Control and Loading During
      Dynamic Sporting Actions in Patients With Athletic Groin Pain?
AB  - CONTEXT: Chronic athletic groin pain (AGP) is common in field sports and has been
      associated with abnormal movement control and loading of the hip and pelvis
      during play. A single-leg squat (SLS) is commonly used by clinicians to assess
      movement control, but whether it can provide insight into control during more
      dynamic sporting movements in AGP patients is unclear. OBJECTIVE: To determine
      the relationships between biomechanical measures in an SLS and the same measures
      in a single-leg drop landing, single-leg hurdle hop, and a cutting maneuver in
      AGP patients. DESIGN: Cross-sectional study. SETTING: Biomechanics laboratory.
      PATIENTS: 40 recreational field-sports players diagnosed with AGP. INTERVENTION:
      A biomechanical analysis of each individual's SLS, drop landing, hurdle hop, and
      cut was undertaken. MAIN OUTCOME MEASURES: Hip, knee, and pelvis angular
      displacement and hip and knee peak moments. Pearson product-moment correlations
      were used to examine relationships between SLS measures and equivalent measures
      in the other movements. RESULTS: There were no significant correlations between
      any hip or pelvis measure in the SLS with the same measures in the drop landing,
      hurdle hop, or cut (r = .03-.43, P > .05). Knee frontal- and transverse-plane
      angular displacement were related in the SLS and drop landing only, while knee
      moments were related in the SLS, drop-landing, and hurdle hop (r = .50-.67, P <
      .05). CONCLUSION: For AGP patients, an SLS did not provide meaningful insight
      into hip and pelvis control or loading during sporting movements that are
      associated with injury development. The usefulness of an SLS test in the
      assessment of movement control and loading in AGP patients is thus limited. The
      SLS provided moderate insight into knee control while landing and therefore may
      be of use in the examination of knee-injury risk.

PMID- 25946709
TI  - Transfer of Alopecia Areata to C3H/HeJ Mice Using Cultured Lymph Node-Derived
      Cells.

PMID- 25946708
TI  - Comparison of in-patient costs for children treated on the AAML0531 clinical
      trial: A report from the Children's Oncology Group.
AB  - BACKGROUND: A better understanding of drivers of treatment costs may help
      identify effective cost containment strategies and prioritize resources. We aimed
      to develop a method for estimating inpatient costs for pediatric patients with
      acute myeloid leukemia (AML) enrolled on NCI-funded Phase III trials, compare
      costs between AAML0531 treatment arms (standard chemotherapy +/- gemtuzumab
      ozogamicin (GMTZ)), and evaluate primary drivers of costs for newly diagnosed
      pediatric AML. PROCEDURE: Patients from the AAML0531 trial were matched on
      hospital, sex, and dates of birth and diagnosis to the Pediatric Health
      Information Systems (PHIS) database to obtain daily billing data. Inpatient
      treatment costs were calculated as adjusted charges multiplied by hospital
      specific cost-to-charge ratios. Generalized linear models were used to compare
      costs between treatment arms and courses, and by patient characteristics.
      RESULTS: Inpatient costs did not differ by randomized treatment arm. Costs varied
      by course with stem cell transplant being most expensive, followed by
      Intensification II (cytarabine/mitoxantrone) and Induction I
      (cytarabine/daunorubicin/etoposide). Room/board and pharmacy were the largest
      contributors to inpatient treatment cost, representing 74% of the total cost.
      Higher AML risk group (P = 0.0003) and older age (P < 0.0001) were associated
      with significantly higher daily inpatient cost. CONCLUSIONS: Costs from external
      data sources can be successfully integrated into NCI-funded Phase III clinical
      trials. Inpatient treatment costs did not differ by GMTZ exposure but varied by
      chemotherapy course. Variation in cost by course was driven by differences in
      duration of hospitalization through room/board charges as well as increased
      clinical and pharmacy charges in specific courses.

PMID- 25946711
TI  - Induction of homologous and cross-reactive GII.4-specific blocking antibodies in
      children after GII.4 New Orleans norovirus infection.
AB  - Noroviruses (NoVs) are major causative agents of acute gastroenteritis (AGE) in
      children worldwide and the most common viral cause of AGE in countries where
      rotavirus incidence has been eliminated by vaccination. Previous infections with
      the dominant GII.4 NoV genotype confer only partial protection against evolving
      immune escape variants that emerge every few years. The objective of this work
      was to investigate GII.4-specific homologous and cross-reactive antibody
      responses in young children after NoV GII.4-2009 New Orleans (NO) infection.
      Virus-like particles (VLPs) representing GII.4-1999, GII.4-2009 NO, and GII.4
      2012 Sydney genotypes were used in ELISA and histo-blood group antigen blocking
      assays to examine acute and convalescent sera of five children <2 years of age
      infected with GII.4-2009 NO. GII.4-2009 NO infection induced IgG seroconversion
      to all three tested NoV GII.4 variants. Homologous blocking antibodies to GII.4
      2009 NO were detected in each convalescent sera. Fourfold increase in cross
      blocking antibodies to GII.4-2012 Sydney was observed in 4/5 subjects, but no
      child developed cross-blocking antibodies to GII.4-1999. In conclusion,
      antibodies induced in young children after norovirus GII.4 infection are targeted
      against the causative variant and may cross-protect against strains that are
      closely related, but not with more distinct and earlier GII.4 genotypes.

PMID- 25946710
TI  - Oxypurinol-Specific T Cells Possess Preferential TCR Clonotypes and Express
      Granulysin in Allopurinol-Induced Severe Cutaneous Adverse Reactions.
AB  - Allopurinol, a first-line drug for treating gout and hyperuricemia, is one of the
      leading causes of severe cutaneous adverse reactions (SCARs). To investigate the
      molecular mechanism of allopurinol-induced SCAR, we enrolled 21 patients (13
      Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and 8 drug
      reaction with eosinophilia and systemic symptoms (DRESS)), 11 tolerant controls,
      and 23 healthy donors. We performed in vitro T-cell activation assays by
      culturing peripheral blood mononuclear cells (PBMCs) with allopurinol,
      oxypurinol, or febuxostat and measuring the expression of granulysin and IFN
      gamma in the supernatants of cultures. TCR repertoire was investigated by next
      generation sequencing. Oxypurinol stimulation resulted in a significant increase
      in granulysin in the cultures of blood samples from SCAR patients (n=14) but not
      tolerant controls (n=11) or healthy donors (n=23). Oxypurinol induced T-cell
      response in a concentration- and time-dependent manner, whereas allopurinol or
      febuxostat did not. T cells from patients with allopurinol-SCAR showed no
      crossreactivity with febuxostat. Preferential TCR-V-beta usage and clonal
      expansion of specific CDR3 (third complementarity-determining region) were found
      in the blister cells from skin lesions (n=8) and oxypurinol-activated T-cell
      cultures (n=4) from patients with allopurinol-SCAR. These data suggest that, in
      addition to HLA-B*58:01, clonotype-specific T cells expressing granulysin upon
      oxypurinol induction participate in the pathogenesis of allopurinol-induced SCAR.

PMID- 25946712
TI  - Focus on perfectionism in female adolescent anorexia nervosa.
AB  - OBJECTIVE: Maudsley Family-Based Treatment (FBT) for anorexia is successful for
      between 50 and 80% of adolescents. To improve this success rate, various
      approaches to augmenting the treatment have been proposed. METHOD: In this study,
      we describe the treatment of three girls with FBTaugmented with a module focusing
      on perfectionism, defined as personally prescribed or socially derived irrational
      and rigid expectations and exceedingly high standards of self performance.
      Multiple times across the 1 year of treatment, girls completed the measures of
      perfectionism and other outcomes. RESULTS: The results were optimistic for
      remission, and showed reductions in girls? perfectionism and obsessional and
      rigid thinking.

PMID- 25946715
TI  - Reviews.

PMID- 25946713
TI  - Ammonia and urea excretion in the swimming crab Portunus trituberculatus exposed
      to elevated ambient ammonia-N.
AB  - In the present study of the swimming crab Portunus trituberculatus exposed to 0,
      1, and 5 mg L(-1) NH4Cl, the effects of ammonia exposure on ammonia and urea
      content in hemolymph; activity of H(+)-ATPase (subunit A) and Na(+)/K(+)-ATPase
      (alpha-subunit) (NKA) in gills; mRNA expression levels of the crustacean Rh-like
      ammonia transporter (Rh), K(+) Channel, Na(+)/K(+)/2Cl(-) co-transporter (NKCC),
      Na(+)/H(+)-exchanger (NHE), urea transporter (UT) and vesicle associated membrane
      protein (VAMP) in gills were investigated. The ultrastructure of gills was also
      evaluated. All these results in this study showed a dose-dependent effect with
      ammonia exposure concentration. The data displayed a significant increase in
      hemolymph ammonia and urea concentrations under ammonia exposure. The up
      regulation of Rh mRNA together with up-regulation of K(+)-channel mRNA, NKA
      activity, down-regulation of NKCC and NHE mRNA suggested a coordinated protective
      response to maintain a relatively low ammonia concentration in the body fluids
      during ambient ammonia exposure. The up-regulation of VAMP, H(+)-ATPase activity
      along with the ultrastructure of gills suggested a mechanism of exocytotic
      ammonia excretion that may exit in the gill of P. trituberculatus. An increased
      production of urea and the up-regulated expression of UT suggested that the crab
      can detoxify elevated ammonia levels in the body fluids into urea when pathways
      of ammonia excretion are decreased after long term ammonia exposure.

PMID- 25946716
TI  - Reviews.

PMID- 25946717
TI  - Reviews.

PMID- 25946718
TI  - This Month in Aerospace Medicine History.

PMID- 25946719
TI  - Use of intracardiac echocardiography to guide percutaneous transluminal mitral
      commissurotomy: A 20-patient case series.
AB  - OBJECTIVES: To report the efficacy and safety of the use adjunctive intracardiac
      echocardiography (ICE) during percutaneous transluminal mitral commissurotomy
      (PTMC) in patients without transesophageal echocardiography (TEE). BACKGROUND:
      Patients with mitral stenosis are at a high risk of developing a left atrial (LA)
      thrombus. Traditionally, TEE has been used prior to PTMC to identify the presence
      of LA thrombi. There have been no reports of the use of ICE to assess the LA for
      thrombi prior to PTMC. METHODS: We retrospectively reviewed 20 patients who
      underwent ICE prior to PTMC. All PTMC procedures were performed via the antegrade
      transvenous approach using an Inoue balloon. Initially, ICE was used from the
      right atrium to confirm the absence of a thrombus on the left side of the septum
      and was subsequently used to guide the transseptal puncture. Following these
      procedures, the ICE was advanced into the LA through a transseptal sheath to
      visualize the LAA. RESULTS: Visualization of the thrombus/spontaneous echo
      contrast was considered to be diagnostic in all cases. Seventy percent of the
      patients were discharged on day after the procedure. No patients required
      intubation during the procedure, and there were no complications that could be
      attributed to the use of ICE. At six months after the PTMC, the incidence of
      stroke was zero. CONCLUSIONS: ICE-guided PTMC offers excellent visualization of
      the LA and the LAA with satisfactory clinical outcomes and low risk. As a part of
      the PTMC procedure, ICE safely provides a valid alternative to a separate TEE
      procedure.

PMID- 25946721
TI  - Dumbbell-Shaped Epidural Capillary Hemangioma Presenting as a Lung Mass: Case
      Report and Review of the Literature.
AB  - STUDY DESIGN: A case report and literature review. OBJECTIVE: We present the
      fourth case of a spinal epidural capillary hemangioma with a dumbbell-shaped
      appearance in the magnetic resonance image reported in the literature and the
      second presented as a lung mass. SUMMARY OF BACKGROUND DATA: Hemangiomas are
      congenital vascular malformations that pathologists frequently consider to be
      hamartomatous malformations. Hemangiomas of the spine are usually lesions of the
      vertebral bodies, but they can sit in other locations such as the intramedullary
      or epidural space. Purely epidural hemangiomas are rare and most of them are of
      cavernous type. METHODS: We present a 67-year-old female with a thoracic dumbbell
      shaped capillary hemangioma with both foraminal and intrathoracic extensions,
      whose presentation was pleural effusion associated with mediastinal mass
      suggestive of pulmonary neoplasia. Surgical treatment consisted of total removal
      en bloc of the lesion. RESULTS: Microscopic evaluation showed a fibrofatty tissue
      with a proliferation of vascular structures that were generally of a small size,
      with areas of myxoid appearance. To date, there have been 8 epidural capillary
      hemangiomas of the thoracic and lumbar spine reported in the literature, and only
      3 of them were dumbbell-shaped with extraforaminal extension. CONCLUSION: It is
      important to consider the diagnosis of hemangiomas in the differential diagnosis
      of epidural lesions with dumbbell-shaped appearance in the magnetic resonance
      image, especially at the thoracic level. It is a benign and potentially curable
      disease and the most appropriate surgical treatment is en bloc resection of the
      entire lesion. They are usually presented as a progressive myelopathy, so early
      treatment may prevent permanent neurological deficits. LEVEL OF EVIDENCE: 5.

PMID- 25946720
TI  - Adult Spinal Deformity Patients Recall Fewer Than 50% of the Risks Discussed in
      the Informed Consent Process Preoperatively and the Recall Rate Worsens
      Significantly in the Postoperative Period.
AB  - STUDY DESIGN: Recall of the informed consent process in patients undergoing adult
      spinal deformity surgery and their family members was investigated prospectively.
      OBJECTIVE: To quantify the percentage recall of the most common complications
      discussed during the informed consent process in adult spinal deformity surgery,
      assess for differences between patients and family members, and correlate with
      mental status. SUMMARY OF BACKGROUND DATA: Given high rates of complications in
      adult spinal deformity surgery, it is critical to shared decision making that
      patients are adequately informed about risks and are able to recall preoperative
      discussion of possible complications to mitigate medical legal risk. METHODS:
      Patients undergoing adult spinal deformity surgery underwent an augmented
      informed consent process involving both verbal and video explanations. Recall of
      the 11 most common complications was scored. Mental status was assessed with the
      mini-mental status examination-brief version. Patients subjectively scored the
      informed consent process and video. After surgery, the recall test and mini
      mental status examination-brief version were readministered at 5 additional time
      points: hospital discharge, 6 to 8 weeks, 3 months, 6 months, and 1 year
      postoperatively. Family members were assessed at the first 3 time points for
      comparison. RESULTS: Fifty-six patients enrolled. Despite ranking the consent
      process as important (median overall score: 10/10; video score: 9/10), median
      patient recall was only 45% immediately after discussion and video re-enforcement
      and subsequently declined to 18% at 6 to 8 weeks and 1 year postoperatively.
      Median family recall trended higher at 55% immediately and 36% at 6 to 8 weeks
      postoperatively. The perception of the severity of complications significantly
      differs between patient and surgeon. Mental status scores showed a transient,
      significant decrease from preoperation to discharge but were significantly higher
      at 1 year. CONCLUSION: Despite being well-informed in an optimized informed
      consent process, patients cannot recall most surgical risks discussed and recall
      declines over time. Significant progress remains to improve informed consent
      retention. LEVEL OF EVIDENCE: 3.

PMID- 25946722
TI  - Vertebral Bone Marrow Edema (VBME) in Conservatively Treated Acute Vertebral
      Compression Fractures (VCFs): Evolution and Clinical Correlations.
AB  - STUDY DESIGN: Prospective observational study. OBJECTIVE: To assess (1) the
      evolution of vertebral bone marrow edema (VBME) in patients with A1 vertebral
      compression fractures (VCFs) conservatively treated and (2) the relationship
      between VBME and clinical symptoms, evaluated as Visual Analogue Scale (VAS) back
      pain and Oswestry Disability Index (ODI). SUMMARY OF BACKGROUND DATA: VBME is a
      marker of acute-subacute vertebral fractures. Little is known about the evolution
      of VBME in conservatively managed VCFs, as well as its clinical meaning. METHODS:
      82 thoracic or lumbar VCFs (21 post-traumatic; 61 osteoporotic VCFs), type A1
      according to the AOSpine thoracolumbar spine injury classification system, in 80
      patients were treated with C35 hyperextension brace for 3 months, bed rest for
      the first 25 days. Patients with osteoporotic fractures also received
      antiresorptive therapy and vitamin D supplementation. At 0 (T0), 30 (T1), 60
      (T2), and 90 (T3) days, patients underwent magnetic resonance imaging evaluation
      and clinical evaluation, using VAS for pain and ODI.The paired t test was used to
      compare changes within groups at each follow-up versus baseline. The unpaired t
      test after ANOVA (analysis of variance) was used to compare the 2 groups at each
      follow-up.The association between VBME area, VAS score, and ODI score was
      analyzed by the Pearson correlation test. The tests were 2-tailed with a
      confidence level of 5%. RESULTS: A significant VBME mean area, VAS, and ODI
      scores reduction was recorded at 60 and 90-days follow-ups versus baseline. A
      positive correlation between VBME reduction and clinical symptoms improvement
      (VAS and ODI scores improvement) was found in both traumatic and osteoporotic
      VCFs. CONCLUSION: In benign A1 VCFs conservatively managed, VBME slowly decreases
      in the first 3 months of magnetic resonance imaging follow-up. This VBME
      reduction is related to clinical symptoms improvement. LEVEL OF EVIDENCE: 4.

PMID- 25946723
TI  - Oxidative unzipping of stacked nitrogen-doped carbon nanotube cups.
AB  - We demonstrate a facile synthesis of different nanostructures by oxidative
      unzipping of stacked nitrogen-doped carbon nanotube cups (NCNCs). Depending on
      the initial number of stacked-cup segments, this method can yield graphene
      nanosheets (GNSs) or hybrid nanostructures comprised of graphene nanoribbons
      partially unzipped from a central nanotube core. Due to the stacked-cup structure
      of as-synthesized NCNCs, preventing complete exposure of graphitic planes, the
      unzipping mechanism is hindered, resulting in incomplete unzipping; however,
      individual, separated NCNCs are completely unzipped, yielding individual nitrogen
      doped GNSs. Graphene-based materials have been employed as electrocatalysts for
      many important chemical reactions, and it has been proposed that increasing the
      reactive edges results in more efficient electrocatalysis. In this paper, we
      apply these graphene conjugates as electrocatalysts for the oxygen reduction
      reaction (ORR) to determine how the increase in reactive edges affects the
      electrocatalytic activity. This investigation introduces a new method for the
      improvement of ORR electrocatalysts by using nitrogen dopants more effectively,
      allowing for enhanced ORR performance with lower overall nitrogen content.
      Additionally, the GNSs were functionalized with gold nanoparticles (GNPs),
      resulting in a GNS/GNP hybrid, which shows efficient surface-enhanced Raman
      scattering and expands the scope of its application in advanced device
      fabrication and biosensing. 

PMID- 25946724
TI  - Attachment, emotion regulation, and adaptation to breast cancer: assessment of a
      mediational hypothesis.
AB  - OBJECTIVES: This study examines the links between attachment, adaptation to
      breast cancer, and the mediating role played by emotional regulation processes.
      METHODS: Participants were 127 women with breast cancer recruited in two public
      hospitals of Porto and at the Portuguese Cancer League. Women completed measures
      of attachment, quality of life, and emotion regulation. Path models were used to
      examine the associations between the constructs and to test the mediational
      hypotheses. RESULTS: Significant associations were found between attachment and
      adaptation. Dimensions of emotion regulation totally or partially mediated the
      associations between attachment and adaptation outcomes. Attachment security
      effects on interpersonal relations were totally mediated by communicating
      emotions. Also, attachment anxiety effect on physical well-being was totally
      mediated by rumination. Attachment avoidance effects on psychological outcomes
      were totally mediated by emotional control and partially mediated by
      communicating emotions for the case of interpersonal relations. CONCLUSIONS: This
      study highlights the importance of addressing emotional regulation jointly with
      attachment to deepen the comprehension of the relational processes implicated in
      adaptation to breast cancer. Results supported a mediational hypothesis,
      presenting emotional regulation processes as relevant dimensions for the
      understanding of attachment associations with adaptation to breast cancer.

PMID- 25946725
TI  - Umbilical cord blood: advances and opportunities. Introduction.

PMID- 25946726
TI  - Immune reconstitution after cord blood transplantation: peculiarities, clinical
      implications and management strategies.
AB  - Umbilical cord blood (UCB) is now widely used as an alternative hematopoietic
      stem cell source for patients lacking closely matched related or unrelated adult
      donors. UCB transplantation has traditionally been associated with delayed
      engraftment, poor immune reconstitution and consequent increased risk of
      infection. More recent clinical studies, however, suggest that conditioning
      regimens and in particular the omission of in vivo T-cell depletion may play a
      crucial role in post-transplant T-cell expansion, facilitating a uniquely rapid
      immune recovery after UCB transplantation. The peculiar characteristics of UCB
      cells, the importance of thymic function and the role of conditioning regimens
      and graft-versus-host disease influencing immune reconstitution are described.
      The last part of the review reports available data on UCB, as well as third-party
      peripheral blood derived anti-viral cell therapy, which provides a novel approach
      to rescue UCB recipients with viral complications in the post-transplant period.

PMID- 25946727
TI  - Electrogenerated thin films of microporous polymer networks with remarkably
      increased electrochemical response to nitroaromatic analytes.
AB  - Thin films of microporous polymer networks (MPNs) have been generated by
      electrochemical polymerization of a series of multifunctional carbazole-based
      monomers. The microporous films show high Brunauer-Emmett-Teller (BET) surface
      areas up to 1300 m2 g(-1) as directly measured by krypton sorption experiments. A
      correlation between the number of polymerizable carbazole units of the monomer
      and the resulting surface area is observed. Electrochemical sensing experiments
      with 1,3,5-trinitrobenzene as prototypical nitroaromatic analyte demonstrate an
      up to 180 times increased current response of MPN-modified glassy carbon
      electrodes in relation to the nonmodified electrode. The phenomenon probably
      involves intermolecular interactions between the electron-poor nitroaromatic
      analytes and the electron-rich, high surface area microporous deposits, with the
      electrochemical reduction at the MPN-modified electrodes being an adsorption
      controlled process for low scan rates. We expect a high application potential of
      such MPN-modified electrodes for boosting the sensitivity of electrochemical
      sensor devices.

PMID- 25946729
TI  - Why aerospace medicine is important.

PMID- 25946730
TI  - Real-time effects of normobaric, transient near-anoxia on performance.
AB  - INTRODUCTION: Recent physiological incidents involving pilots of high performance
      fighter aircraft have raised the question of whether inadvertent, short bursts of
      significantly reduced oxygen could negatively impact real-time performance. This
      study evaluated normobaric, real-time performance in the setting of transient
      near-anoxia to inform future countermeasure development. METHODS: The study was
      performed on 12 healthy subjects without significant medical history. Following
      collection of baseline data, real-time performance changes were evaluated during
      sequentially increasing periods of near-anoxic gas exposure (F(I)0(2) = 1%) using
      a computer-based performance assessment tool. Both room air and 100% oxygen were
      used as the prebreathe/recovery gases. Statistical analysis was performed on the
      results. RESULTS: Under normobaric conditions, subjects inspiring up to five near
      anoxic breaths showed no significant performance decrement in either accuracy or
      effective actions per minute. Mean accuracy up to five near-anoxic breaths was
      0.67 (SD = 0.01) as compared to a baseline mean of 0.68 (SD = 0.02). Hyperoxia
      had a protective effect on subject physiological response to near anoxia.
      DISCUSSION: These normobaric findings offer an assessment of real-time
      performance changes in the setting of transient, near-anoxic gas exposure.
      Overall, the results help inform the design of increasingly complex aircraft
      oxygen delivery systems in terms of how tightly such systems must match the sea
      level gas equivalent with increasing altitude. This is particularly relevant as
      such systems are being called upon to ensure safe aircrew operations across an
      expanding operational flight envelope.

PMID- 25946731
TI  - Breath-hold times in air compared to breath-hold times during cold water
      immersions.
AB  - INTRODUCTION: Given the effects of cold water immersion on breath-hold (BH)
      capabilities, a practical training exercise was developed for
      military/paramilitary personnel completing a helicopter underwater egress
      training (HUET) program. The exercise was designed to provide firsth and
      experience of the effects of cold water exposure on BH time. METHODS: After
      completing the required HUET, 47 subjects completed two BH testing sessions as
      well as a short questionnaire. The first BH was completed while standing on the
      pool deck. The second BH was completed while fully immersed (face down) in 2-3
      degrees C water. There were 40 of the volunteers who also breathed from an
      emergency breathing system (EBS) while in the cold water. RESULTS: Results
      demonstrated that BH capabilities in cold water were significantly lower than
      those in ambient air. A significant correlation was also found between BH in air
      and the difference in cold water vs. air BH capabilities, which suggests that
      subjects who can hold their breath the longest in air experienced the greatest
      decrease in BH when immersed. Results indicate that 92% of the subjects reported
      that the practical cold water immersion exercise had a high value. Finally, 58%
      of those who used the EBS reported that it was harder to breathe in cold water
      than while in the training pool (approximately 22 degrees C). DISCUSSION: The BH
      times for this group were similar to those reported in previous cold water
      immersion studies. Based on the questionnaire results, it is possible, when
      carefully applied, to include a practical cold water immersion exercise into
      existing HUET programs.

PMID- 25946732
TI  - Fluid loading effects on temporal profiles of cardiovascular responses to head
      down tilt.
AB  - BACKGROUND: Susceptibility of healthy astronauts to orthostatic hypotension and
      presyncope is exacerbated upon return from spaceflight. Up to 64% of astronauts
      experience postflight orthostatic intolerance. A promising countermeasure for
      postflight orthostatic intolerance is fluid loading by giving crew salt tablets
      and water prior to re-entry. The primary goal of the current study was to
      determine the optimal time window prior to re-entry when individual crew-persons
      would initiate fluid loading. METHODS: There were 16 subjects who were given two
      6-h exposures, with and without fluid loading (conditions), to head-down tilt
      (HDT) to simulate the effects of microgravity. Pre- and post-HDT stand tests of
      orthostatic tolerance were given. Physiological measurements recorded included
      heart rate, blood pressure, peripheral blood volume, total peripheral resistance,
      and impedance cardiography. Echocardiography measures of stroke volume and
      cardiac output were also recorded. RESULTS: Data were analyzed with three-way
      repeated measures ANOVA (gender * condition * time). Only the condition * time
      interaction was significant for mean arterial pressure. Post hoc multiple
      comparison tests revealed significant increases in mean arterial pressure
      occurred between hours 1 and 3 of HDT after fluid loading (10 mmHg higher than no
      fluid). DISCUSSION: These findings indicate that the optimal time for crew to
      begin fluid loading is within 1 to 3 h prior to re-entry. Nonsignificant trends
      of multiple cardiovascular responses showed similar time profiles. The large
      amount of individual variability suggests that fluid loading alone may be an
      inadequate countermeasure for all crewmembers. Further research is needed on
      possible adjunct methods of tailoring countermeasures for individuals.

PMID- 25946733
TI  - Statin use and the development of acute mountain sickness.
AB  - INTRODUCTION: Our prior publication suggested that elevated serum concentrations
      of low-density lipoprotein (LDL) was protective against the development of acute
      mountain sickness (AMS) while an inflammatory response was contributory to its
      development. The use of 3-hydroxy-3-methylglutaryl-coenzyme-A-reductase
      inhibitors ("statins") may be of interest to those traveling to altitude-these
      medications will lower serum LDL concentrations, but are also reported to have
      anti-inflammatory properties. METHODS: Prior to flying from sea level to the
      South Pole (~10,498.7 ft or 3200 m) during the austral summer months of 2005-2006
      and 2006-2007, the 248 subjects provided informed consent. Questionnaires related
      to AMS symptoms, acetazolamide use, personal history, and anthropometrics were
      paired with results from blood samples. Statin use was reported by six subjects
      who were matched for age, sex, altitude of residence, and acetazolamide use with
      seven subjects not using a statin. RESULTS: No significant differences were
      identified in any of the matched variables between the groups. No statin users
      reported symptoms of AMS while 57% of participants not using a statin did report
      AMS symptoms (P = 0.03). No significant difference was noted between LDL levels
      in the statin group (108.3 +/- 61.0) as compared to the group not taking statins
      (104.6 +/- 22.1) (P = 0.88). DISCUSSION: Our previous results suggested that
      elevated LDL was protective while an inflammatory response was contributory with
      respect to AMS development. The present results suggest that statin use may
      provide protection against AMS symptoms, possibly through an anti-inflammatory
      property, despite its lipid-lowering capacity. Harrison MF, Johnson BD. Statin
      use and the development of acute mountain sickness.

PMID- 25946734
TI  - Gender differences in navigational memory: pilots vs. nonpilots.
AB  - INTRODUCTION: The coding of space as near and far is not only determined by arm
      reaching distance, but is also dependent on how the brain represents the
      extension of the body space. Recent reports suggest that the dissociation between
      reaching and navigational space is not limited to perception and action but also
      involves memory systems. It has been reported that gender differences emerged
      only in adverse learning conditions that required strong spatial ability.
      METHODS: In this study we investigated navigational versus reaching memory in air
      force pilots and a control group without flight experience. We took into account
      temporal duration (working memory and long-term memory) and focused on working
      memory, which is considered critical in the gender differences literature.
      RESULTS: We found no gender effects or flight hour effects in pilots but observed
      gender effects in working memory (but not in learning and delayed recall) in the
      nonpilot population (Women's mean = 5.33; SD= 0.90; Men's mean = 5.54; SD= 0.90).
      We also observed a difference between pilots and nonpilots in the maintenance of
      on-line reaching information: pilots (mean = 5.85; SD=0.76) were more efficient
      than nonpilots (mean = 5.21; SD=0.83) and managed this type of information
      similarly to that concerning navigational space. In the navigational learning
      phase they also showed better navigational memory (mean = 137.83; SD=5.81) than
      nonpilots (mean = 126.96; SD=15.81) and were significantly more proficient than
      the latter group. DISCUSSION: There is no gender difference in a population of
      pilots in terms of navigational abilities, while it emerges in a control group
      without flight experience. We found also that pilots performed better than
      nonpilots. This study suggests that once selected, male and female pilots do not
      differ from each other in visuo-spatial abilities and spatial navigation.

PMID- 25946735
TI  - The risk of prostate cancer in pilots: a meta-analysis.
AB  - BACKGROUND: Aviation exposes pilots to various occupationally related hazards,
      including ionizing radiation and chemical combustion. The possible increased risk
      of prostate cancer among pilots in comparison to the general population is a
      subject of debate. This systematic review and meta-analysis aimed to determine
      the quality of supporting evidence and magnitude of this association. METHODS:
      All studies pertaining to prostate cancer in pilots were retrieved from multiple
      databases and from a manual search. Any study that assessed the incidence of
      prostate cancer relative to the incidence in the general population was included
      regardless of language or size. A random effect model was used to pool relative
      risks (RR) across studies. Heterogeneity was assessed using the Q statistic and
      I2. RESULTS: Eight studies with a low risk of bias were included in the meta
      analysis. Pilots had an increased risk of developing prostate cancer compared to
      the general population [RR 2.0; 95% confidence interval (CI), 1.5-2.7]. The
      analysis was associated with substantial heterogeneity (I2 = 79%). Several
      subgroups had significantly increased risk, such as African American pilots (RR
      10.00; 95% CI, 5.04-19.86) and military pilots (RR 3.30; 95% CI, 2.03-5.39).
      CONCLUSION: Pilots are at least twice as likely to develop prostate cancer
      compared to the general population. The implications of these findings are
      important considering the high prevalence of prostate cancer and the large number
      of pilots in the workforce.

PMID- 25946736
TI  - Hypobaric hypoxia: effects on contrast sensitivity in high altitude environments.
AB  - BACKGROUND: Effects of hypobarism and hypoxia on visual performance and mainly on
      contrast sensitivity (CS) are well known. The purpose of this study was to
      compare the adjustments of corneal thickness in hypobaric hypoxia conditions with
      changes in contrast sensitivity. METHODS: There were 12 healthy, emmetropic
      subjects assigned to the 14(th) Wing Aircrew based in Pratica di Mare AFB (Rome,
      Italy) who were evaluated for changes occurring in central corneal thickness
      (CCT), measured by portable ultrasonic pachymeter, and CS, assessed after reading
      the standard Pelli-Robson charts, during modification of atmospheric pressure
      and, therefore, of oxygen partial pressure. RESULTS: Hypobaric hypoxia conditions
      in pilots raised CCT (550 MUm to 600 MUm) and reduced CS (1.95 log to 1.05 log)
      in a statistically significant result. DISCUSSION: The study demonstrated that
      hypoxia and variations of atmospheric pressure may produce corneal edema,
      including changes of CCT and, correlatively, CS reduction.

PMID- 25946737
TI  - Dry bulb temperature effects on crew well-being in long-duration ad hoc platform
      flights.
AB  - PURPOSE: U.S. combat activities in Iraq and Afghanistan saw the implementation of
      multiple ad hoc systems incorporated onto commercial aerial platforms for
      supporting operations. The use of manned platforms, many of which were never
      intended for the long-duration missions to which they have been applied, has had
      human factor and aviation life support equipment (ALSE) implications. The
      physiological stress-inducing nature of high temperatures (> 40 C) is one such
      concern. This study assessed cockpit temperatures in one such platform during
      actual combat missions over Iraq. METHODS: Three missions were flown in Iraq
      during 2011 on an ad hoc aerial platform and dry bulb temperature readings were
      recorded periodically at head height at different crew stations. Relative
      humidity was also recorded. RESULTS: Temperatures demonstrated wide variability
      during mission profiles, ranging from > 40 degrees C to 15 degrees C. Ground heat
      soaked cabin temperatures were measured as high as 48 degrees C. High
      temperatures could be experienced for up to an hour prior to departure.
      DISCUSSION: While ad hoc aerial platform use has operational merits, the lack of
      adequate crew life support systems on such platforms can pose thermal risks to
      the aircrews. More detailed investigation is needed to determine core temperature
      response of aircrews during such operations and platform specific ALSE
      requirements to better support aircrew mission effectiveness.

PMID- 25946738
TI  - Confinement vs. isolation as analogue environments for Mars missions from a human
      ethology viewpoint.
AB  - INTRODUCTION: This study compares observational data from two situations designed
      as planetary exploration missions: the Tara expedition and the Mars-500
      experiment. We examined the issue of distinct environmental factors, isolation
      vs. confinement, which may have different or similar impacts on crews' behavioral
      manifestations for long-term adaptation, such as on a Mars mission. The Tara
      expedition was a 507-d polar drift of the Tara schooner embedded in the Arctic
      ice with two successive periods of summer and winter-over in an isolated
      environment. The Mars-500 experiment took place in Moscow and was a 520-d
      simulation of a trip to Mars, the Mars landing, and the return trip to Earth in a
      confined environment. METHODS: We used the ethological method based on
      observation, description, and quantification of individual and interindividual
      behaviors. These events were scored from video recordings made during daily life
      activities and aggregated according to the summer period and to the outgoing trip
      for the whole crew (N = 6) for each situation, respectively. RESULTS: We did not
      observe differences in the frequency of facial expressions and in the duration of
      body interactions. Conversely, there were differences in the frequency of
      collateral acts and in the duration of personal actions with the highest levels
      during the Mars-500 experiment (0.52 /min and 41,799 s); the highest level of
      visual interactions was observed during the Tara expedition (33,167 s).
      DISCUSSION: We found that confinement generates stress manifestations vs.
      isolation, that isolation enhances social relashionships vs. confinement, and
      that the crew adapted positively to both environments.

PMID- 25946739
TI  - Isolated perivesicular hematoma after military parachuting.
AB  - BACKGROUND: Isolated perivesicular hematomas are uncommonly described and not an
      injury typically reported in the literature after parachuting or skydiving. CASE
      REPORT: Herein, we described a series of three patients with isolated
      perivesicular hematomas sustained after military parachuting. All three patients
      were managed nonoperatively after a somewhat prolonged hospital course. Despite
      the lack of orthopedic injuries, all required physical therapy consultation and
      required an assisting device to aide with ambulation at the time of discharge.
      For all three individuals, follow-up imaging months after the injury demonstrated
      a continued presence of the hematoma. Clinically, the patients continued to have
      ambulatory and urological difficulties for several months after their injury.
      DISCUSSION: This injury pattern is uncommonly reported in the literature. An
      appropriate index of suspicion must be maintained or there may be a delay in
      diagnosis. Management of these injuries requires coordinated care between the
      trauma service, urology, and physical therapy.

PMID- 25946740
TI  - Portable radiography: a reality and necessity for ISS and explorer-class
      missions.
AB  - On ISS missions and explorer class missions, unexpected medical and surgical
      emergencies could be disastrous. Lack of ability to rapidly assess and make
      critical decisions affects mission capability. Current imaging modalities on ISS
      consist only of ultrasound. There are many acute diagnoses which ultrasound alone
      cannot diagnose. Portable X-Ray imaging (radiography) technology has advanced far
      enough to where it is now small enough, cheap enough, and accurate enough to give
      diagnostic quality images sent wirelessly to the onboard computer and on Earth
      for interpretation while fitting in something the size of a briefcase. Although
      further research is warranted, Portable Radiography is an important addition to
      have on ISS and future Explorer Class Missions while maintaining a very small
      footprint.

PMID- 25946743
TI  - You're the flight surgeon.

PMID- 25946742
TI  - You're the flight surgeon.

PMID- 25946744
TI  - Origin of the first naval flight surgeons.

PMID- 25946745
TI  - This month in aerospace medicine history.

PMID- 25946748
TI  - Science and the state: a programme. 1915.

PMID- 25946747
TI  - Ceria/POLYMER hybrid nanoparticles as efficient catalysts for the hydration of
      nitriles to amides.
AB  - We report the synthesis of ceria/polymer hybrid nanoparticles and their use as
      effective supported catalysts for the hydration of nitriles to amide, exemplified
      with the conversion of 2-cyanopiridine to 2-picolinamide. The polymeric cores,
      made of either polystyrene (PS) or poly(methyl methacrylate) (PMMA), are prepared
      by miniemulsion copolymerization in the presence of different functional
      comonomers that provide carboxylic or phosphate groups: acrylic acid, maleic
      acid, and ethylene glycol methacrylate phosphate. The functional groups of the
      comonomers generate a corona around the main polymer particle and serve as
      nucleating agents for the in situ crystallization of cerium(IV) oxide. The
      obtained hybrid nanoparticles can be easily redispersed in water or ethanol. The
      conversion of amides to nitriles was quantitative for most of the catalytic
      samples, with yields close to 100%. According to our experimental observations by
      high-performance liquid chromatography (HPLC), no work up is needed to separate
      the product from unreacted substrate. The substrate remains absorbed on the
      catalyst surface, whereas the product can be easily separated. The catalysts are
      shown to be recyclable and can be reused for a large number of cycles without
      loss in efficiency. 

PMID- 25946749
TI  - [Pain caused by otorhinolaryngologic diseases].

PMID- 25946750
TI  - [Optokinetics].

PMID- 25946751
TI  - [Etiology and treatment for laryngeal cancer].

PMID- 25946752
TI  - [Surgery for tongue cancer].

PMID- 25946753
TI  - The green (and winding) road. It's been a year since Colorado and Washington
      legalized recreational marijuana, and not all that was predicted has come to pass
      -with some surprises along the way.

PMID- 25946754
TI  - Q & A with grower Tim Cullen [interview by Mary Winter].
AB  - Tim Cullen is CEO and founder of the Colorado Harvest Company and Evergreen
      Apothecary, an expanding business in Denver that grows and sells marijuana. His
      most lucrative store averages 200 to 300 sales a day, with roughly 80 percent
      being for recreational purposes. The former high school biology teacher became
      interested in marijuana when he saw how it helped his father control the pain and
      nausea of Crohn's Disease, which Cullen himself developed later. He began growing
      marijuana in his basement in Colorado, where growing medical marijuana for
      personal use has been legal for 12 years. He now grows his plants in 55,000
      square feet in four warehouses.

PMID- 25946755
TI  - Supreme Court watch: redistricting commissions and federal health care exchanges
      are the focus of two important cases now in the hands  of Supreme Court justices.

PMID- 25946756
TI  - [Skin ulcers in a returning traveler].
AB  - We present the case of a 71 year old man returning from a back-packer trip in
      exotic countries. He presented several non-healing legs ulcers for three months.
      After many investigations, the bacterial culture gave us the answer.

PMID- 25946758
TI  - The technology hype cycle.

PMID- 25946757
TI  - Educating for industry: a call to action for bio-/biomedical engineering
      professors and students.

PMID- 25946759
TI  - The tango: how its perception developed over the decades.

PMID- 25946760
TI  - Propelling your career.

PMID- 25946761
TI  - Edibles: for experts only? Ingesting marijuana, as opposed to smoking it, has
      come a long way since the days of homemade pot brownies.

PMID- 25946762
TI  - The familial Mediterranean fever (FMF) 50 score: does it work in a controlled
      clinical trial? Re-analysis of the trial of rilonacept for patients with
      colchicine-resistant or intolerant FMF.
AB  - BACKGROUND: The familial Mediterranean fever 50 score (FMF50) score was recently
      devised to define response to treatment and as an outcome measure for clinical
      trials of FMF. OBJECTIVES: To examine the performance of the FMF50 score in a
      previously published trial of rilonacept for patients whose FMF was resistant or
      intolerant to colchicine. METHODS: We re-analyzed the data from our controlled
      trial of rilonacept vs. placebo in 14 patients with colchicine-resistant or
      intolerant FMF using the FMF50 score as the primary outcome. The FMF50 score
      required improvement by >= 50 in five of six criteria (attack frequency, attack
      duration, global patient assessment, global physician assessment, frequency of
      attacks with arthritis, and levels of acute-phase reactants) without worsening of
      the sixth criterion. RESULTS: In the original trial rilonacept was considered
      effective according to the primary outcome measure (differences in the attack
      frequency) with eight analyzable patients considered responders and four as non
      responders. According to the FMF50 score, only two participants would have been
      considered respondersto rilonacept, and one to placebo. Only two participants had
      >= 50% differences between rilonacept and placebo in five criteria. The major
      explanation for non-response to treatment was that with rilonacept the duration
      of attack decreased by >= 50% in only 2 participants and 5 participants had no
      attacks of arthritis either during screening (before randomization) or during
      treatment with rilonacept. CONCLUSIONS: The proposed FMF50 score did not
      differentiate well between responders and non-responders compared to the a priori
      defined primary outcome measure in this successful controlled study.

PMID- 25946763
TI  - Acceptance of forensic imaging in Israel.
AB  - BACKGROUND: Forensic imaging was officially introduced in Israel in 2011.
      Religious and cultural opposition to autopsies prevails in most of the population
      of Israel. OBJECTIVES: To examine the extent to which forensic imaging has been
      accepted as an adjuvant or partial replacement of forensic autopsy, particularly
      among those opposed to forensic autopsy. METHODS: The study was conducted in the
      pediatric population. Data were collected from the National Center of Forensic
      Medicine and Assaf Harofeh Medical Center during the 18 month period following
      the introduction of forensic imaging (group A). The data were compared to those
      of the previous 18 months (group B). The examined parameters were cases
      submitted, examined, autopsied or imaged depending on family consent. RESULTS:
      Consent to autopsy was similar in both groups (A = 56% vs. B = 54%). In group A,
      consent for imaging was 24% of all cases, and of those imaged 77% underwent
      autopsy. Of those examined externally only, 16% consented to imaging. For 7% of
      the total cases in group A, estimation of cause of death was based on virtopsy
      alone. CONCLUSIONS: In a country with a high level of religious and cultural
      opposition to autopsy, it is a challenge to add forensic imaging to the pediatric
      forensic investigation. Those consenting to forensic imaging are more likely to
      be those consenting to autopsy. Consent for forensic imaging only was given in 7%
      of cases. Greater efforts should be invested to educate and inform the public
      regarding the benefits of virtual autopsy and the importance of data acquired
      from forensic images.

PMID- 25946764
TI  - Clinical characteristics and survival of patients with diabetes mellitus
      following non-traumatic lower extremity amputation.
AB  - BACKGROUND: Diabetes mellitus-related lower extremity amputation is a major
      complication severely affecting patient survival and quality of life. OBJECTIVES:
      To analyze epidemiological and clinical trends in the incidence and survival of
      lower extremity amputations among diabetes patients. METHODS: We conducted a
      retrospective observational cohort study of 565 consecutive diabetes patients who
      underwent their first non-traumatic lower extremity amputation between January
      2002 and December 2009. RESULTS: Major amputations were performed in 316 (55.9%)
      patients: 142 above the knee (25.1%) and 174 below (30.8%); 249 (44.1%) had a
      minor amputation. The incidence rates of amputations decreased from 2.9 to 2.1
      per 1000 diabetes patients. Kaplan-Meier survival analysis showed that first year
      mortality rates were lower among patients with minor amputations (31.7% vs.
      39.6%, P = 0.569). First year mortality rates following below-knee amputation
      were somewhat lower than above-knee amputation (33.1 vs. 45.1%, respectively).
      Cox regression model of survival at 1 year after the procedure found that age (HR
      1.06 per year, 95% CI 1.04-1.07, P < 0.001), above-knee amputation (HR 1.36, 95%
      CI 1.01-1.83, P = 0.045) and ischemic heart disease (HR 1.68, 95% CI 1.26-2.24, P
      < 0.001) significantly increased one year mortality risk. CONCLUSIONS: In this
      population-based study the incidence rate of non-traumatic amputations in
      diabetes patients between January 2002 and December 2009 decreased slightly.
      However, one year mortality rates after the surgery did not decline and remained
      high, stressing the need for a multidisciplinary effort to prevent amputations in
      diabetes patients.

PMID- 25946765
TI  - Long-term follow-up of patients with scleroderma interstitial lung disease
      treated with intravenous cyclophosphamide pulse therapy: a single-center
      experience.
AB  - BACKGROUND: Scleroderma lung disease (ILD-SSc) is treated mainly with
      cyclophosphamide (CYC). The effectiveness of CYC was judged after 12-24 months in
      most reports. OBJECTIVES: To analyze the effect of monthly intravenous CYC on
      pulmonary function tests including forced vital capacity (FVC) and diffusing lung
      capacity (DLCO), as well as Rodnan skin score (mRSS), during long-term follow-up.
      METHODS: We retrospectively collected the data on 26 ILD-SSc patients who began
      CYC treatments before 2007. Changes in FVC, DLCO and mRSS before treatment, and
      at 1,4 and 7 years after completion of at least six monthly intravenous CYC
      treatments for ILD-SSc were analyzed. RESULTS: Mean cumulative CYC dose was 8.91
      +/- 3.25 G. More than 30% reduction in FVC (0%, 8%, and 31% of patients), DLCO
      (15%, 23%, 31%), and mRSS (31%, 54%, 62%) at years 1, 4 and 7 was registered.
      During the years 0-4 and 4-7, annual changes in FVC, DLCO and mRSS were 3.2 vs.
      0.42% (P < 0.040), 4.6 vs. 0.89% (P < 0.001), and 1.8 vs. 0.2 (P = 0.002). The
      greatest annual FVC and DLCO reduction over the first 4 years correlated with
      mortality (P = 0.022). There were no differences in the main variables regarding
      doses of CYC (< 6 G and > 6 G). CONCLUSIONS: In patients with ILD-SSc, CYC
      stabilized the reduction of FVC during treatment, but this effect was not
      persistent. The vascular characteristic of ILD-SSc (DLCO) was not affected by CYC
      treatment. CYC rapidly improved the mRSS. This effect could be achieved with at
      least 6 G of CYC. Higher rates of annual reduction in FVC and DLCO in the first 4
      years indicate the narrow window of opportunity and raise the question regarding
      ongoing immunosuppression following CYC infusions.

PMID- 25946766
TI  - Can renal hemangiomas be diagnosed preoperatively?
AB  - BACKGROUND: Renal hemangiomas are rare benign tumors seldom distinguished from
      malignant tumors preoperatively. OBJECTIVES: To describe the Memorial Sloan
      Kettering Cancer Center (MSKCC) experience with diagnosing and treating renal
      hemangiomas, and to explore possible clinical and radiologic features that can
      aid in diagnosing renal hemangiomas preoperatively. METHODS: Patients with renal
      hemangiomas treated at MSKCC were identified in our prospectively collected renal
      tumor database. Descriptive statistics were used to describe the patient
      characteristics and the tumor characteristics. All available preoperative imaging
      studies were reviewed to assess common findings and explore possible
      characteristics distinguishing benign hemangiomas from malignant renal tumors
      preoperatively. RESULTS: Of 6341 patients in our database 15 were identified.
      Eleven (73%) were males, median age at diagnosis was 53.3 years, and the affected
      side was evenly distributed. All but two patients were treated surgically. The
      mean decrease in estimated glomerular filtration rate (eGFR) after surgery was
      36.3%; one patient had an abnormal presurgical eGFR and only two patients had a
      normal eGFR after surgery. We could not identify radiographic features that would
      make preoperative diagnosis certain, but we did identify features characteristic
      of hepatic hemangiomas that were also present in some of the renal hemangiomas.
      CONCLUSIONS: Most renal hemangiomas cannot be distinguished from other common
      renal cortical tumors preoperatively. In select cases a renal biopsy can identify
      this benign lesion and the deleterious effects of extirpative surgery can be
      avoided.

PMID- 25946767
TI  - A novel heart rate variability algorithm for the detection of myocardial
      ischemia: pilot data from a prospective clinical trial.
AB  - BACKGROUND: Heart rate variability (HRV) analysis has been shown to be a
      predictor of sudden cardiac death and all-cause mortality in patients with
      cardiac disease. OBJECTIVES: To examine whether newer HRV analysis algorithms, as
      used by the HeartTrends device, are superior to exercise stress testing (EST) for
      the detection of myocardial ischemia in patients without known coronary artery
      disease (CAD). METHODS: We present pilot data of the first 100 subjects enrolled
      in a clinical trial designed to evaluate the yield of short-term (1 hour) HRV
      testing for the detection of myocardial ischemia. The study population comprised
      subjects without known CAD referred to a tertiary medical center for EST with
      single-photon emission computed tomography (SPECT) myocardial perfusion imaging
      (MPI). All patients underwent a 1 hour electrocardiographic acquisition for HRV
      analysis with a HeartTrends device prior to ESTwith MPI. Sensitivity,
      specificity, and positive and negative predictive values (PPV and NPV,
      respectively) were calculated for EST and HRV analysis, using MPI as the gold
      standard for the non-invasive detection of myocardial ischemia. RESULTS: In this
      cohort 15% had a pathologic MPI result. HRV analysis showed superior sensitivity
      (85%), PPV (50%) and NPV (97%) as compared to standard EST (53%, 42%, 90%,
      respectively), while the specificity of the two tests was similar (86% and 85%,
      respectively). The close agreement between HRV and MPI was even more pronounced
      among patients > 65 years of age. CONCLUSIONS: Our pilot data suggest that the
      diagnostic yield of the novel HeartTrends HRV algorithm is superior to
      conventional EST for the non-invasive detection of myocardial ischemia.

PMID- 25946768
TI  - Spectrum of GBA mutations in patients with Gaucher disease from Slovakia:
      identification of five novel mutations.
AB  - BACKGROUND: Gaucher disease is the most common lysosomal storage disorder and is
      caused by a deficiency of the enzyme glucocerebrosidase. Enzyme deficiency leads
      to the accumulation of undegraded substrates, mainly in cells of the monocyte/
      macrophage lineage, which is responsible for the clinical manifestations of the
      disease. To date, no study has attempted to identify the mutation spectrum of the
      glucocerebrosidase gene (GBA) in Slovak patients OBJECTIVES: To identify
      mutations in 14 Slovak patients with confirmed glucocerebrosidase deficiency.
      METHODS: Using molecular genetics methods PCR-RFLP (polymerase chain reaction
      restriction fragment length polymorphism) and direct sequencing of coding region
      GBA we identified the spectrum of mutations in our patients. RESULTS: Five
      mutations (N370S, L444P, G377S, D409H and RecNciI) accounted for 75% of the
      mutant alleles. The remaining 25% were rare and probably individual mutations.
      CONCLUSIONS: The mutational spectrum in our patients is similar to that observed
      in other European countries and corresponds to a Caucasian population, with
      N370S, L444P, RecNciI being the most common. Interestingly, mutation G377S was
      more frequent in our patients as compared to other published data. The C4W, L96P,
      H311N, 745delG and 1127_1128delTT mutations are described here for the first time
      in Gaucher disease, contributing to the panel of published GBA mutations.

PMID- 25946769
TI  - Neuropsychiatric manifestations associated with anti-endothelial cell antibodies
      in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized
      by multisystem involvement due to immune dysregulation. Neuropsychiatric systemic
      lupus erythematosus (NPSLE) includes neurological syndromes involving the
      central, peripheral and autonomic nervous system, as well as psychiatric
      syndromes observed in patients with SLE in which other causes have been excluded.
      The pathogenesis of NPSLE has been attributed to many different mechanisms. In
      particular, autoantibody-mediated vasculopathy seems to play a major role in the
      pathogenesis of the clinical features. Several autoantibody specificities have
      been reported in the serum and cerebrospinal fluid of NPSLE patients. Recently,
      we demonstrated an association between serum antiendothelial antibodies (AECA)
      and psychosis or depression in SLE patients, strengthening the notion of a
      possible role of this class of autoantibodies in the pathogenesis of the disease.
      The study of these autoantibodies could be a useful diagnostic and prognostic
      tool in patients with NPSLE.

PMID- 25946770
TI  - Hunger striking inmates and detainees, and medical ethics.

PMID- 25946771
TI  - Early diagnosis in an unusual presentation of Takayasu's arteritis.

PMID- 25946773
TI  - Food protein-induced enterocolitis syndrome due to oysters ingestion.

PMID- 25946772
TI  - Valve-sparing aortic root surgery in a patient with Loeys-Dietz syndrome.

PMID- 25946774
TI  - Fat malabsorption due to bile acid synthesis defect.

PMID- 25946775
TI  - Candida albicans in peritoneal fluid in a patient with hepatic encephalopathy.

PMID- 25946776
TI  - Hemifacial microsomia and lung hypoplasia.

PMID- 25946780
TI  - Bariatric patient care. When an obese patient is transported, what can be done
      with his scooter?

PMID- 25946777
TI  - Brain hemorrhage as presenting feature of Takayasu's arteritis in an African
      girl.

PMID- 25946781
TI  - Delivering ALS care on the fire line. How Kern County, CA, developed an ALS fire
      line paramedic program.

PMID- 25946783
TI  - Alternative options for patient transport. Specially designed ATVs and UTVs for
      EMS use enable EMS providers to get to patients virtually anywhere.

PMID- 25946782
TI  - Integrating home care hospice & EMS. Partnerships with MIH-CP programs can help
      avoid needless hospital visits.

PMID- 25946784
TI  - Addressing ambulance standards. New ambulance design & safety standards will be
      in place by 2016--the question is, what will they look like? Addressing ambulance
      standards.

PMID- 25946785
TI  - EMS.O.S. We need a secret way to ask for help--but what?.

PMID- 25946786
TI  - New proposed shared savings regs win friends, influence organizations.

PMID- 25946787
TI  - EEOC challenges some wellness programs.

PMID- 25946788
TI  - Cancer agents taken orally pose adherence problems despite ease of
      administration.

PMID- 25946789
TI  - Businesses seek new ways to manage diabetes.

PMID- 25946790
TI  - Should specialty drugs be shifted from medical to pharmacy benefit?

PMID- 25946791
TI  - When it comes to new drugs, if providers and payers snooze, they lose.

PMID- 25946792
TI  - A conversation with John Marcille. A front row seat for 22 years.

PMID- 25946793
TI  - Managing the high cost of obesity.

PMID- 25946794
TI  - Costs and benefits of bundled community-based screening for carotid artery
      stenosis, peripheral artery disease, and abdominal aortic aneurysm.
AB  - PURPOSE: Perform an initial formal assessment of the costs and benefits of
      bundled cardiovascular screening. Primarily, determine the relative importance of
      data uncertainties to the integrity ofmodeled outcomes associated with bundled
      screening for carotid artery stenosis (CAS), peripheral artery disease (PAD), and
      abdominal aortic aneurysm (AAA); secondarily, establish parameters around
      potential costs and outcomes benefits of this screening bundle. DESIGN: A
      decision-analysis framework composed of four decision tree submodels with
      transition probabilities specific to four age- and gender-specific subgroups.
      Model transition probabilities for each of the four submodels are based on the
      prevalence of all possible combinations of the presence or absence of moderate
      CAS, significant CAS, PAD, and AAA, and the likelihood of appropriate or
      inappropriate medical follow-up. METHODOLOGY: Evaluates a hypothetical self
      funded employer with 10,000 beneficiaries and who is considering whether to
      provide bundled cardiovascular health screenings. Screenings would be performed
      in addition to any other medical screenings commonly performed by physicians to
      assess cardiovascular risk. Determine costs and catastrophic events (death,
      myocardial infarction, stroke, other cardiovascular-related events, amputation
      events) for these self-funded hypothetical beneficiaries aged >= 50 years and <
      65 years. RESULTS: The model predicts approximately $54 million in health care
      costs over 10 years for the control cohort and $51 million for the screening
      cohort, representing a 5.2% reduction in 10-year health care spending due to
      screening. CONCLUSION: This initial analysis predicts robust cost and health
      benefits associated with the decision to provide bundled cardiovascular health
      screening to a self-funded employer's beneficiaries aged >= 50 years and < 65
      years. Further analyses are necessary to better quantify the magnitude of the
      cost and health benefits.

PMID- 25946795
TI  - Less invasive, more informative monitoring breakthroughs on way.

PMID- 25946796
TI  - Zetia study keeps PCSK9s on approval course.

PMID- 25946798
TI  - Half of Americans could be obese by 2030.

PMID- 25946799
TI  - [Sex in old age - is that acceptable?].

PMID- 25946797
TI  - Two-pronged approach holds promise against peripheral arterial disease.

PMID- 25946800
TI  - [A role reversal].

PMID- 25946801
TI  - [Using the sexuality power source].

PMID- 25946802
TI  - [Breaking a taboo].

PMID- 25946803
TI  - ["Often the reaction is too late"].

PMID- 25946804
TI  - [Improving quality and reducing cost: the ERAS concept].

PMID- 25946805
TI  - ["Students want to create the future"].

PMID- 25946806
TI  - [Changing addictive behavior in small steps].

PMID- 25946807
TI  - [Six steps to greater safety].

PMID- 25946808
TI  - ["Providing courage in hardship"].

PMID- 25946809
TI  - [Optimizing potential at all levels].

PMID- 25946810
TI  - [Technology yes, technology no?].

PMID- 25946811
TI  - [More dementia departments are needed].

PMID- 25946812
TI  - [Exemplary educator and companion. Hildegard Steuri].

PMID- 25946813
TI  - [Evidence based care reduces risks].

PMID- 25946814
TI  - [The salt of life].

PMID- 25946815
TI  - [The freedom to be oneself].

PMID- 25946816
TI  - [Health promotion outside the school milieu].

PMID- 25946817
TI  - [Travel to the land of shadows].

PMID- 25946818
TI  - [Hope despite a precarious life].

PMID- 25946819
TI  - [A gain in terms of autonomy and assurance].

PMID- 25946820
TI  - [Quality assurance of independent nurses].

PMID- 25946821
TI  - [Distributing tasks according to skills].

PMID- 25946822
TI  - [The corporate culture is decisive].

PMID- 25946823
TI  - ["A tree may hide the forest... a steak also"].

PMID- 25946824
TI  - [Sexuality: a human right].

PMID- 25946825
TI  - [A life marked by major breakthroughs].

PMID- 25946826
TI  - [A middle to long-term clinical study on pars flaccida and pars tensa
      cholesteatoma using survival analysis].
AB  - The current clinical study was performed on 311 cases of pars flaccida and 89
      cases of pars tensa cholesteatoma which were treated with canal wall
      reconstructed tympanoplasty between 1991 and 2012. The average follow-up time of
      these patients was 5.3 years. Since follow-up periods were different in each case
      and some censored patients were involved, we used survival analysis on this study
      to discuss the cumulative rates of disease-free successful cases and the rates of
      recurrent cholesteatoma throughout the postoperative course. The disease-free
      successful cases were defined as those cases in which patients were both out of
      re-operation with recurrent and residual cholesteatoma and out of revision
      operation with another problem, furthermore, maintained good hearing outcome.
      Based on the criteria set by the Japan Otological Society (2010), the cases that
      satisfied the following were evaluated as good hearing results; (a) a successful
      case in which preoperative bone conduction was used, and (b) a case in which the
      postoperative air-bone gap was within 20dB after tympanoplasty for chronic otitis
      media. The analysis results were shown for each of (a) and (b). 1. In pars
      flaccida cholesteatoma, the 5-year survival rate of successful case was (a) 76.1%
      and (b) 83.9%, the 10-year survival rate was (a) 58.9% and (b) 73.0%. In pars
      tensa cholesteatoma, the 5-year survival rate of successful cases was (a) 57.7%
      and (b) 63.5%, the 10-year rate was (a) 42.1% and (b) 56.9%. A significant
      difference was seen between pars flaccida and pars tensa cholesteatoma (p <
      0.001). 2. In pars flaccida cholesteatoma, the 5-year recurrence rate was 7.6%
      and the 10-year rate was 15.3%, and the recurrence rate increased gradually
      throughout the follow-up period. On the other hand, in pars tensa cholesteatoma,
      the increase in the recurrence rate reached a peak 15.8% at 5.5 years after the
      surgery. A long-term follow-up is necessary when evaluating the clinical results
      after tympanoplasty.

PMID- 25946827
TI  - [Preoperative evaluation of surgery for intractable aspiration based on the
      prognostic nutritional index].
AB  - Because there is no absolute indicator of the nutritional status and prognosis in
      patients with severe aspiration problems, it is quite difficult to arrive at a
      true long-time prognosis. By performing surgery for intractable aspiration on
      such patients, both the prognosis and QOL of the patients could be expected to
      improve. In our department, we have experienced patients dying within 6 months
      after surgery. In these cases, the patient's preoperative nutritional status was
      not good. Therefore, we consider that, when we adopt this procedure, there should
      be some indicators we should use which could have an effect on the prognosis of
      such nutritionally-challenged patients. In patients who underwent surgery for
      intractable aspiration; we examined the relationship between their survival and
      the prognostic nutritional index (PNI) which is an indicator of the risk of
      complications such as post-operative events in the surgical field. We
      investigated the relationship between the prognosis and the postoperative
      indicators of each of the following: WBC, CRP, serum albumin level, and PNI. Out
      of a total of 31 cases, the average O-PNI of eight cases in which death occurred
      was 29.45, and the average of six cases in which death occurred within 6 months
      after surgery was 28.26. The average O-PNI of the survivors was 36.01. A
      significant association was noted between the early postoperative deaths and some
      of the four indicators namely that serum albumin level and O-PNI. Based on the
      ROC curve, the O-PNI offered higher precision than the albumin level. The cut-off
      value of the O-PNI value for early postoperative mortality rate was 32. The early
      postoperative mortality rate was 44.4% in patients with less than 32 O-PNI in the
      preoperative examination, but if it were O-PNI 32 or more, the early
      postoperative mortality rate was 9.1%, significantly lower. Therefore, O-PNI
      could be useful as one of the prognostic evaluation factors in the case of
      preoperative surgery for intractable aspiration. Based on the O-PNI score, it was
      possible to evaluate the survival benefit associated with this operative
      procedure. We showed a treatment algorithm based on the preoperative O-PNI value.
      We believe there is a necessity to develop preoperative effective nutritional
      therapy as a future issue.

PMID- 25946828
TI  - [A clinical study of cases diagnosed as being oropharyngeal carcinoma after
      cervical mass extirpation/biopsy].
AB  - In the case of oropharyngeal carcinoma, patients may present with symptoms
      similar to cervical lymphadenopathy, and the primary lesion may only be diagnosed
      after cervical mass extirpation/biopsy. We retrospectively analyzed the clinical
      course in 11 oropharyngeal carcinoma patients that were diagnosed after cervical
      mass extirpation/biopsy between 1998 and 2013. Before the diagnosis was made of
      oropharyngeal carcinoma, a cervical lymph node biopsy was performed in six
      patients; the lymph node was extirpated due to an initial diagnosis of lateral
      cervical cyst in four patients; and neck dissection was performed due to an
      initial diagnosis of primary unknown carcinoma in one patient. The primary tumor
      site in the oropharynx was the palatine tonsil in six patients and the lingual
      tonsil in five patients. Five of six patients with palatine tonsil carcinoma and
      three of five patients with lingual tonsil carcinoma were found to be positive
      for human papillomavirus (HPV). The duration from cervical lymph node
      extirpation/biopsy to final diagnosis was 1 to 13 months. All patients finally
      underwent radiation therapy or chemoradiotherapy, and they had no recurrence or
      metastasis. As the incidence of HPV-related oropharyngeal carcinoma increases,
      the number of oropharyngeal carcinomas assumed to be cervical lymphadenopathy due
      to the presenting symptoms may increase. It is important to investigate the
      oropharynx thoroughly so as to adequately differentiate the possibility of
      oropharyngeal carcinoma from that of cervical lymphadenopathy. Metastatic lymph
      nodes might present as cysts in cases of oropharyngeal carcinoma, it is therefore
      necessary to take the potential for metastatic lymph nodes in the oropharyngeal
      cancer into consideration when differentiating this disease from cervical cyst
      shaped lesions.

PMID- 25946829
TI  - [A case report: primary nasal tuberculosis].
AB  - A 62-year-old female visited us complaining of lacrimination and the swelling of
      the left side of the nasal dorsum. Granulation tissues were seen on the anterior
      lateral wall of the left nasal cavity, and an imaging study revealed a mass
      occupying both the left nasal cavity and the anterior ethmoid sinuses invading
      the face with erosion of the nasal bone. Histological examination showed an
      epithelioid granuloma without caseous necrosis which mostly suggested
      sarcoidosis. The affected lesions became larger 11 months after the initial
      examination, and a biopsy was performed again, which revealed the same
      pathological findings. Although the biopsy specimen was negative based on the PCR
      findings, tubercle bacillus was detected in the culture 7 weeks later. The
      patient was finally diagnosed as having primary tuberculosis of the nose and
      paranasal sinuses because systemic examination showed no evidence of tuberculosis
      in other areas. She was treated with antituberculosis medication, and the
      affected nasal lesions disappeared. It is important to perform a biopsy and
      tissue culture repeatedly when we encounter an intractable and undiagnosed
      disease in the nasal cavity.

PMID- 25946830
TI  - [A case of intraorbital solitary fibrous tumor resected successfully with
      preoperative arterial embolization].
AB  - The solitary fibrous tumor (SFT) is a rare spindle cell neoplasm derived from
      mesenchymal cells. It sometimes recurs clinically, and is categorized as an
      'intermediate malignancy' tumor under the WHO (World Health Organization)
      classification of soft tissue tumors. Several studies have reported on
      intraorbital SFTs, but none of them has pointed out the utility of preoperative
      arterial embolization in the case of an intraorbital SFT. A 75-year-old man, who
      had received a dacryocystectomy for a benign tumor in the right lacrimal sac 30
      years previously, visited our hospital complaining of lower eyelid swelling and
      lachrymation that had persisted for a year. CT and MRI revealed an intraorbital
      lesion, and the open biopsy specimen showed dense growth of spindle cells, which
      turned out to be an SFT by immunohistochemistry based on the findings. After
      preoperative embolization of the infraorbital artery, we removed the tumor with a
      skin incision on the lower rim of the orbit with little bleeding. The surgical
      specimen revealed that the tumor was close to a lacrimal canaliculus, which
      suggested the tumor originated from the lacrimal apparatus considering the
      patient's past history. He was followed up for three months without recurrences.

PMID- 25946832
TI  - [Comparative biochemistry of process of ageing in men and women].
AB  - In the research of a number of biochemical indicators in 858 men and 899 women
      aged from 20 till 70 years divided into 6 compared groups depending on age and
      gender clear distinctions in the dynamics of the components of the lipid status,
      status of lipid peroxidation and antioxidant activity of the blood system, the
      content of middlemolecular peptides are revealed. Simultaneous determination of
      the biological age of the subjects also revealed a distinct gender differencies
      testifying to lower rate of aging of men, despite the probability of earlier, in
      comparison with women, development of dislipidemia and atherosclerosis.
      Association of the received gender distinctions both with changes of level of
      estrogen in women due to menopause and with the peculiarities of stressful
      impacts on male and female organism in different age periods is supposed.

PMID- 25946831
TI  - [Activity of the enzymes which take part in aldehyde catabolism in the
      mitochondria of skeletal muscle in rats of different ages and its modulation
      during stress].
AB  - The purpose of this study was a comparative investigation of activity of enzymes,
      which take part in utilization of endogenous aldehydes in mitochondrial fraction
      of femoral muscle in intact and immobilized rats of different age. It has been
      shown that 12-months-old (adult) rats have high basal levels of NAD-aldehyde
      dehydrogenase, NADH-aldehyde reductase and glutathione transferase activity in
      mitochondrial fraction of femoral muscle. An increased of NAD-aldehyde
      dehydrogenase activity emerges during immobilization stress in adult rats. These
      changes contribute to enhancing the effectiveness of utilization of carbonyl
      products of free radical oxidation in mitochondria of skeletal muscle of 12
      months-old rats during stress. Immobilization of old and pubertal rats, is
      accompanied by a certain arise in metabolic preconditions, leading to
      accumulation of endogenous aldehydes in mitochondria, and, as a result, to the
      injury of muscular fibers and an increase in manifestation of sarcopenia.

PMID- 25946833
TI  - [Lamellar complex changes in the human basal forebrain and hypothalamic nuclei
      neurons in different age groups].
AB  - In the present study the lamellar complex (LC, Golgi complex) changes in the
      major cholinergic nuclei of the human basal forebrain - the nucleus basalis of
      Meynert (NBM), the vertical nucleus of the diagonal band of Broca (VDB) and
      hypothalamus--the tuberomamillary (TMN), the medial mammillary (MMN) and
      supraoptic (SON) nuclei were analyzed considering the WHO aging classification.
      The increase in the size of the LC was present in NBM, MMN and SON in the 3rd age
      group of elderly people (60-74 years of age), in the VDB--in the 4th group (75-89
      years of age), whereas in the TMN LC changes were not apparent. In conclusion,
      the WHO aging classification reflects the LC values age ranges and can be used to
      estimate age-related alterations of this parameter. The increase in the size of
      the neuronal LC in elderly people may represent the compensatory reaction of
      neuroplasticity triggered by the aging process.

PMID- 25946834
TI  - [Role of the change of daily rhythms of adrenaline and noradrenaline
      concentration in blood in the mechanism of accelerated aging in hypopinealizm
      induced by a long period of day and night lighting].
AB  - In young adult male rabbits circadian rhythms change of blood concentrations of
      adrenaline and noradrenaline in the dynamics of hypopinealism development induced
      by a long period (5 months) twenty-four-hour lighting of low intensity (30-40
      lux) were studied. It was found that the light in the night leads to a
      significant increase in the levels of both catecholamines, which indicates on the
      activation of the sympathoadrenal system (SAS), just as it occurs in aging and
      stress (stress-age-syndrome by V.V. Frolkis). Daily features of SAS reactions to
      light stress were revealed. Based on these data it can be concluded that one of
      the reduction mechanisms of life expectancy at hypopinealizm is excessive and
      prolonged activation of SAS.

PMID- 25946836
TI  - [Development of cataract in the ontogeny of senescence-accelerated oxys rats--the
      basic selection trait of this strain].
AB  - Previous research showed that clinical manifestations of cataract in OXYS rats
      closely match those of senile cataract in humans, which led to using this rat
      strain in studies on the pathogenesis of this disease and on efficacy of new
      therapeutic methods. The aim of the present work was to analyze morphological
      changes in the lens of OXYS rats at different stages of cataractogenesis by means
      of light microscopy and to assess mRNA levels of alphaA- and alphaB-crystallin
      genes in the lens. We studied the animals at age 20 days (no clinical signs of
      cataract), age 3 months (cataract prevalence is 100%), and at age 12 months (when
      in the majority of OXYS rats, aberrations in the lens correspond to pronounced
      stages of this disease). Age-matched Wistar rats served as controls. In the lens
      of 20-day-old OXYS rats, we detected minor aberrations in the packing of cortical
      fibers, signs of alterations in the activity of transport systems and/ or cell-to
      cell contacts as well as a compensatory, by all appearances, increase in the
      density of the lens epithelium and upregulation of the alphaA- and alphaB
      crystallin genes. At age 3 months, there were noticeable aberrations (and at 12
      months, significantly enhanced aberrations) in the structure of the lens capsule
      and in organization of the cortical fibers of the lens, whereas a-crystallin
      expression dipped below than in the Wistar rats. Recently, we reported
      downregulation of a-crystallin gene expression in the retina of OXYS rats. Early
      cataract is the basic selection trait of this strain; continued selection for
      this trait led to the development of a constellation of signs of premature aging.
      These observations suggest that manifestations of cataract--early development of
      age-related diseases--may be linked to systemic changes in the expression and
      function of crystallins.

PMID- 25946835
TI  - [Preparation stimulating hair growth possibly acts by inhibiting hair follicle
      ageing experiments on mice and transcriptome analysis].
AB  - Preparation stimulating hair growth (PSHG) was studied on mice of various strains
      (Balb/c, CBA, C57BI/6, and outbred). It was shown that a long-term (44 months)
      application of PSHG does not reliably affect the appearance of young healthy mice
      but does induce increase in the hair follicle size. No adverse consequences of
      the PSHG application were observed. Naturally occurring propagating regenerative
      hair waves peculiar to mice were preserved. In older mice (more than 2 years)
      with signs of alopecia, application of PSHG caused an overgrowing of bald patches
      within two months. Transcriptome analysis of the PSHG effect performed in
      fibroblast cell culture showed that PSHG stimulates processes of tissue
      development and remodeling. These observations together with previous findings
      showing that PSHG stimulates autophagy and induces death of cells subjected to
      oxidative stress may suggest that the mechanism of the PSHG effect involves
      stimulation of regeneration of skin and its derivatives owing to more efficient
      elimination of senescent and damaged follicle cells.

PMID- 25946837
TI  - [Assessment of diagnostic scales in cardiovascular patients being at home social
      service from the position of geriatric syndromes].
AB  - The obtained data, from a position of geriatric syndromes, testify to need of
      including of simple estimated scales of a self-rating of health and cognitive
      disorders in the program of inspection of the elderly patients being on home
      social service. The special attention in group of elderly patients with arterial
      hypertension should be paid to widowers who have a low self-rating of health.

PMID- 25946839
TI  - [Molecular mechanisms of combined extremely radiofrequency and infrared therapy
      in various age patients with chronic parodontitis].
AB  - The influence of extreme radiofrequency millimeter microwave (EHF) and infrared
      (IR) electromagnetic emanation on the molecular markers of cell renovation (Ki67,
      p53) and proinflammatory cytokine TNF-alpha expression in the buccal cells of
      various age patients with chronic parodontitis was investigated. The results show
      that EHF- and IR-electromagnetic emanation increased Ki67 proliferative marker
      expression and decreased expression of proapoptosis protein p53 and
      proinflammatory cytokine TNF-alpha in the buccal epithelium of young, middle-aged
      and elderly people with chronic parodontitis. The data obtained open the new
      ability for patogenetic treatment of various age patients with chronic
      parodontitis using the EHF- and IR-electromagnetic emanation method.

PMID- 25946838
TI  - [Tripeptides slow down aging process in renal cell culture].
AB  - The mechanism of geroprotective effect of peptides AED and EDL was studied in
      ageing renal cell culture. Peptide AED and EDL increase cell proliferation,
      decreasing expression of marker of aging p16, p21, p53 and increasing expression
      of SIRT-6 in young and aged renal cell culture. The reduction of SIRT-6 synthesis
      in cell is one of the causes of cell senescence. On the basis of experimental
      data models of interaction of peptides with various sites of DNA were
      constructed. Both peptides form most energetically favorable complexes with
      d(ATATATATAT)2 sequences in minor groove of DNA. It is shown that interaction of
      peptides AED and EDL with DNA is the cause of gene expression, encoded marker of
      ageing in renal cells.

PMID- 25946840
TI  - [Impact of tetrapeptide pancragen on endocrine function of the pancreas in old
      monkeys].
AB  - Significant increase of the elderly in the demographic structure of a modern
      society is one of the main reasons for increase in the number of patients with
      diabetes type 2 and impaired glucose tolerance. The purpose of this research was
      to study impact of Pancragen (tetrapeptide Lys-Glu-Asp-Trp) on endocrine function
      of the pancreas of non-human primates, female rhesus monkeys, and to elucidate
      the possibil- ity of its use for correction age-related dysfunction of pancreatic
      islet apparatus. In old animals after the glucose administration (standard dose)
      in control period, a reduced glucose "disappearance" rate and a higher values of
      insulin and C-peptide peaks (5 and 15 min after the glucose injection) were
      observed in comparison with young animals in similar experiments. Pancragen
      administration (50 MUg/animal per day during 10 days, intramuscularly) to old
      monkeys caused markedly increased the glucose "disappear- ance" rate, normalized
      the plasma insulin and C-peptide dynamics in response to glucose administration.
      The recovering effect of Pancragen on the function of the pancreas partially
      remained 3 weeks after discontinuation of the drug. Thus, Pancragen is a
      promising factor for restoring the age-related endocrine dysfunction of primates.

PMID- 25946841
TI  - [Behavioral response of older women in a stochastic environment].
AB  - The article presents the results of studies of the behavioral response in 63
      elderly women. With the help of a computer complex for psychophysiological
      studies KPFK-99 "Binatest" we estimated figures of restructuring strategies of
      decision making in a stochastic environment. The leading psychophysiological
      mechanisms of behavioral response of older women in a stochastic environment are
      presented as a high-speed component of decision-making process, and search
      activity as a dynamic component of motivational orientation dominates over the
      informational component of the decision-making on the temporary costs.
      Approximately-research activity is random, that does not change the cognitive
      response strategy under uncertainty environment. Women aged 65-74 years are
      observed more time to make decisions and stereotyped of behavior compared to
      women aged 55-64 years.

PMID- 25946842
TI  - [Anxiety-depressive disorders in elderly migrants of the far north in the period
      of re-adaptation to new climatic conditions].
AB  - The article presents the results of studies of the anxious and depressed
      characteristics in elderly migrants of the Far North with arterial hypertension
      in the period of their stay in new climatic conditions with regard to their North
      experience, gender, age and timing of rehabilitation. There was a high frequency
      of disturbing-depressive symptomatology of the surveyed migrants in the Far
      North, the frequency and severity of which increases with age; women migrants of
      Far North are prone to depression 1,8 times, anxiety--3,2 times more often than
      men. With the increase of the period of stay in the new climate and geographical
      conditions, the severity and frequency of occurrence of anxiety and depression
      increase. The obtained results should be taken into account when building
      rehabilitation program and forecasting its effectiveness, while conducting
      psychotherapy and psychological prevention in this group of patients.

PMID- 25946843
TI  - [Physical and psychological health components of elderly and old people and their
      satisfaction with medical and social care].
AB  - The article presents the analysis of physical and psychological health components
      characterizing the quality of life of lonely and living alone people aged 60
      years and older in various settings of medical and social care provision. A
      significant portion of respondents is satisfied with the medical and social care,
      but the physical and psychological health components of the elderly manifest the
      low quality of life, irrespective of the settings of medical and social care
      provision.

PMID- 25946845
TI  - [Prevalence of secondary osteoarthritis in patients with rheumatoid arthritis and
      risk factors for its progression].
AB  - The high prevalence of secondary osteoarthritis in patients with rheumatoid
      arthritis was determined in the trial. Risk factors of comorbidity were revealed:
      age > 45 years, high activity on DAS28, long duration of rheumatoid arthritis,
      morning stiffness > 120 min, pain on VAS > 50 mm. Ultrasound lets not only reveal
      secondary osteoarthritis in early stage, but also determine the stage of the
      accompanying disease.

PMID- 25946844
TI  - [Features of carotid stenting in elderly: predictors of adverse outcomes (review
      of literature)].
AB  - This article presents the review of literature devoted to studying of features of
      carotid angioplasty and stenting (CAS) in older patients. Age has been shown to
      be a predictor of neurological complications during CAS. However, it has been
      demonstrated recently that carotid stenting can be performed safely in patients
      over 70 and even 80 years. According to researchers, predictors of mortality were
      remote (>= 6 months) transient ischemic attack or cerebrovascular accident,
      smoking history, creatinine clearance and hemoglobin level. Better selection of
      patients using the predictors of mortality may help to reduce unwarranted
      procedures and to optimize survival likelihood. Furthermore, CAS could be safely
      performed in elderly patients if certain anatomical and clinical markers such as
      excessive vascular tortuosity, heavy concentric calcification of the lesion and
      decreased cerebral reserve were avoided. However, additional randomized trial
      data are needed.

PMID- 25946846
TI  - [Short peptides stimulate skin cell regeneration during ageing].
AB  - The actual goal of gerontocosmetology is deal with the research of new effective
      and harmless low- molecular substances. The influence of LK and AEDG peptides in
      concentrations 0.05-2.00 ng/ml on organotypic skin cell cultures proliferation in
      young and old animals were investigated. Peptides stimulated skin fibroblasts
      proliferation on 29-45% in skin cell cultures of young and old rats. This effect
      was observed in smaller concentration diapason and level during skin ageing in
      old cell cultures as compared to young cell cultures. These data open new
      approach for creation cosmetology substances in the base of LKand AEDG peptides.

PMID- 25946847
TI  - [Frequency of some diseases and conditions in geriatric patients with coronary
      heart disease and various genotypes of transcription factor 7-like 2 protein].
AB  - In 2009-2010, 98 patients diagnosed with the coronary heart disease, but without
      the expressed metabolic violations, decompensated conditions and diseases were
      surveyed. Patients of 60-90 years were divided by age into two groups: younger
      than 75 years--47 people; 75 years and older--51; there were 41 women and 57 men;
      the ratio between women and men was 1:1.4; average age was 76.0 +/- 1.3 years.
      The average age of women was 76.0 +/- 1.8 years, men--76.1 +/- 2,0 years. 96.0 +/
      2.0% of geriatric patients with CHD complained of steno-cardiac pains in pre
      cardiac area; the excess mass of a body was observed in 43.4 +/- 5.0% of
      geriatric patients with CHD, acute myocardial infarction in the anamnesis was
      noted in 52.5 +/- 6.9% (n = 52); hypertensive illness had 98.0 +/- 1.4% (n = 97).
      Patients had the favorable average levels of lipoproteins of high density (not
      lower than 1 mmol/l). A significant number (79.2 +/- 5.6%) of patients had
      hemodynamically significant narrowing of coronary vessels (75% and more), while
      the area of myocardial hypokinesia was observed in 41.2 +/- 6.9% of patients,
      sharp violation of brain blood circulation was noted in 14.1 +/- 9.8%. Wild type
      homozygous genotype of TCF7L2 gene was detected significantly more often (77.6 +/
      4.7%) in patients of advanced and senile age with CHD, regardless of age group,
      exis-tence of accompanying diseases and conditions, such as previous myocardial
      damage, acute disorders of cerebral circulation and fatty degeneration of the
      liver. However allele of risk T (totally C/Tand T/T) of TCF7L2 gene came to light
      in 22.4 +/- 9.1% of geriatric patients with CHD, that contributes to development
      of a metabolic syndrome in such patients and reduces term of their life.

PMID- 25946848
TI  - [Structural and functional changes of external and intracranial arteries in
      elderly patients of different ethnic groups with ischemic heart disease].
AB  - The present article discusses the problem of structural and functional changes in
      extra-and intracranial arteries in elderly patients with ischemic heart disease
      (CHD) belonging to different ethnic groups before the upcoming coronary
      arteriography research and planned operative intervention. We examined 120
      elderly patients with ischemic heart disease, including 50 patients of Korean
      nationality and 70 patients of Slavic ethnicity. Average values of IMT of the
      right and left CCA patients of South Asian group were significantly lower than
      those of Slavic ethnicity. Elderly patients with CHD the violation of cerebral
      circulation were due to atherosclerotic lesions of the extracranial vessels and
      local hemodynamic disturbances in their area of pathological tortuosity. Korean
      ethnicity elderly patients with CHD were observed more pronounced signs of
      stenosis and deformation of the main arteries of the neck, as well as lower
      collateral reserve of cerebral circulation.

PMID- 25946849
TI  - [Endovascular treatment of bifurcation lesions of the coronary arteries in
      elderly patients: a literature review N-2].
AB  - Intervention in bifurcation coronary arteries disease is complicated kind of
      endovascular treatment of coronary heart disease, especially in patients of
      elderly and senile age. Recently, in the practice of the operating surgeon there
      is a large choice of bifurcation coronary artery stents. This report contains the
      views, features and shortcomings of the presented bifurcation structures. Despite
      the fact that in the Russian Federation bifurcation stents are rarely implanted,
      their use can greatly simplify and accelerate interventional procedures, along
      with the decrease of peri- and postoperative complications.

PMID- 25946850
TI  - [The age aspects of clinical and morphological features of chronic gastritis
      viral and bacterial etiology].
AB  - The article contains the results of studies of clinical and morphological
      features of chronic gastritis of viral and bacterail etiology in age aspects.
      Chronic gastritis when infected with Epstein-Barr virus in elderly patients has
      clinical and morphological differences from chronic gastritis associated with
      Helicobacter pylori infection, consisting in significantly lower severity of
      regenerative changes in the cervical epithelium of the mucous membrane of the
      body and antrum of the stomach, cervical mucosal epithelium of the body, antrum,
      bottom mucosal epithelium of the stomach body; and significantly more rare
      intestinal metaplasia in the stomach and the absence of stromal fibrosis antrum.

PMID- 25946851
TI  - [Autonomic regulation of cardiac rhythm in elderly patients with bronchial
      asthma].
AB  - Evaluation of independent and combined interrelations of bronchial obstruction
      and autonomic regulation of cardiac rhythm in elderly patients with bronchial
      asthma was carried out. Positive correlation of the extent of bronchial
      obstruction and decrease of absolute indices of cardiac rhythm variability was
      established.

PMID- 25946852
TI  - [Tryptophan and nicotinic acid as antioxidants in different age rats brain at the
      immobilization stress].
AB  - It is testified that the intensity of lipid peroxidation (LP) in the brain of old
      and mature rats did not differ significantly. Stress-effects in the form of
      immobilization led to activation of the LP and inhibition of antioxidant activity
      (AOA) in the brain mainly in aged rats. The simultaneous introduction of
      tryptophan and nicotinic acid reduced negative changes of LP and AOA in the brain
      of old rats caused by immobilization stress exposure. In the brain of mature
      rats, the combination of tryptophan and nicotinic acid in normal and
      immobilization decreased the level of LP and increased the intensity of AOA. The
      increased activity of antioxidant system in the brain of rats by complex of
      tryptophan and nicotinic acid demonstrated its protective antioxidant properties.

PMID- 25946853
TI  - [The study of the effectiveness of drug prevention mechanisms of cardiovascular
      aging by cytoflavin].
AB  - The aim of the research was the search of the mechanism of Cytoflavin action in
      patients with isolated systolic arterial hypertension (ISAH) as the aging model.
      The following research methods were applied: the assessment of complaints, 24
      hour arterial pressure monitoring, ultrasound diagnostic, volume sphygmography,
      lipid profiles and coagulogram, molecular phenotyping by MALDI-TOF-TOF-MS. The
      combination of Cytoflavin with standard therapy of ISAH led to the most expressed
      return development of clinical symptoms, the restoration of the haemodynamics,
      structural and geometrical parameters of cardiovascular system, indicators lipid
      profiles and coagulogram in the comparison with patients with ISAH, who accepted
      standard therapy and those of the control groups. Molecular mechanisms of
      Cytoflavin action, including regulation of the activity of cell signaling
      pathways through intermolecular interactions were found. We recommend using
      Cytoflavin together with the standard therapy in treatment of ISAH, which
      provides the action of geroprotectors for cardiovascular system.

PMID- 25946854
TI  - [Modern methods of energy homeostasis correction in elderly patients].
AB  - In the multicenter randomized clinical-instrumental prospective study 185
      patients aged 55-75 years (mean age 68 years) with 94 men and 91 women with
      cerebral infarction were included. All the patients were hospitalized in the
      period from 6 to 24 hours from the time of the debut of clinical symptoms, 42,2%
      of patients scored 14 and above on NIH scale on admission. Patients were
      randomized into 3 groups: 1st group consisted of 64 patients treated as an
      antioxidant by 5% solution of ascorbic acid 2 times a day the recommended dose
      (20 ml/day) for 20 days; 2nd group consisted of 72 patients who received energy
      monitor Cytoflavin in a daily dose of 20 ml (10.0 ml/drip 2 times a day for 10
      days); 3rd group consisted of 49 patients with Cytoflavin therapy extended to 20
      days, moreover from 11th to 20th day the dose was 10 ml/day. Cytoflavin treatment
      was more efficient than ascorbic acid, which can be explained by different
      pharmacologic mechanisms. Treatment with Cytoflavin for 10 days resulted in a
      significant decrease of ischemia zone volume by 25% in average, treatment with
      Cytoflavin for 20 days--by 29%, which manifested in better outcomes in neurologic
      and functional status. Ascorbic acid demonstrated no effect on morphologic
      parameters. Patients having at the time of admission 18-20 points according to
      the NIH and treated with Cytoflavin for 20 days demonstrated significant trend
      towards improvement of the parameters of the neurological status.

PMID- 25946855
TI  - [Melanoma and cancer emergence in persons of 20-60 years against normal quantity
      of cambial cells in morphofunctional zones].
AB  - In age groups from 20 to 60 years cell proliferation and differentiation happen
      in the morphofunctional zone in the electric field excited by 12 pairs of mother
      and daughter cells, which have turned out at cambial cells division. Thus in
      daughter cells the Src SH2 domain necessary both for cytoskeleton formation and
      tyrosinase activization is activated. If the conditions for strengthening of
      tyrosinase activity are created in organism, despite the high maintenance of
      cambial cells, the portion of Src participating in the cytoskeleton building can
      decrease to critical level that will lead to development of a malignant tumor. If
      action of a stimulating factor is quite strong, proliferation of malignant cells
      begins at a stage of melanocyte, and a melanoma occurs. If action of factors is
      long and not strong, more remote descendants of daughter cells proliferate, and a
      cancer appears. For the purpose of normal differentiation of malignant modified
      daughter cells, it is necessary to block tyrosinase. Thus all SH2 domains will go
      on cell cytoskeleton formation.

PMID- 25946856
TI  - [Rehabilitation in elderly people with hearing loss].
AB  - Data about rehabilitation in hearing impaired elderly people living in nursing
      houses in Saint-Petersburg are presented in the article. Hearing aid demand
      depending on age and degree of hearing loss is analyzed and problems of electro
      acoustic correction of hearing loss and possibilities to increase its efficacy in
      studied age group are discussed as well.

PMID- 25946857
TI  - [Left ventricular hypertrophy as a marker of adverse cardiovascular risk in
      persons of various age groups].
AB  - The paper considers modern conceptions about the prognostic value of left
      ventricular hypertrophy (LVH) different types. The role of interaction of
      demographic, hemodynamic, regulatory, intracardiac factors in the formation of
      prognostic peculiarities in patients with different types of LVH is marked. The
      data of own investigations indicating that the left ventricular myocardial mass
      has not less important value in long-term general prognostication than belonging
      to a concentric or eccentric LVH type in elderly patients with hypertension are
      presented. Some data concerning left atrial dilatation as an inalienable
      component of the cardiovascular continuum in essential hypertension are
      submitted. Pathogenic and prognostic contribution of metabolic disorders
      associated with hypertension and abdominal obesity in the development of the
      heart's left parts structural and functional disorders is shown. Issues of long
      term outcome in elderly hypertensive patients with metabolic syndrome taking into
      account the peculiarities of left ventricular geometry are highlighted.

PMID- 25946858
TI  - [Aging and periodontal diseases (review)].
AB  - The review on associative communications of periodontal diseases, aging and age
      associated pathology is submitted. Uniform pathophysiological and pathogenetic
      mechanisms of these processes and their interrelation are analyzed. The question
      of existence of so-called periodontal-systemic connection is discussed. The
      conclusion about need of changing the paradigm of approach for diagnostics and
      treatment of patients with periodontal pathology from tightly specialized
      stomatologic into the interdisciplinary paradigm is drawn. It is especially
      important for the elderly patients having polymorbid pathology in association
      with inflammatory periodontal diseases.

PMID- 25946859
TI  - [Age and gender changes of apatites from human hard tooth tissues].
AB  - Apatites of hard tissues of teeth of persons of different sex and age were
      studied in detail. It is shown that the crystal structure of apatites depends on
      changes in the composition of the enamel that happen during a person's life.
      Limits of the variations of the crystal lattice parameters of the enamel apatites
      connected with the complicate processes of de- and remineralization have been
      determined. On the basis of the identified correlations between chemical
      composition, crystal lattice parameters and age of patients, the complicated
      interrelated isomorphic replacements occurring in the crystal structure of
      apatites of hard tooth tissues during aging were analysed.

PMID- 25946860
TI  - [Features of pathology of the salivary glands in patients of older age groups].
AB  - The article presents the results of a clinical study on the features of age
      related pathology of the salivary glands. 5329 records of patients who were
      hospitalized at the Department of maxillofacial surgery and dentistry in three
      years has been studied. We studied the frequency and reasons for referral to a
      specialized hospital for emergency or routine medical care in connection with the
      pathology of the salivary glands, the structure of diseases of the salivary
      glands. It is shown that people of elderly and senile age turn for specialized
      treatment in the Department of maxillofacial surgery and dentistry more than
      young and middle-aged people.

PMID- 25946861
TI  - [Ensuring of safety of the circulation of medicines in the current demographic
      situation].
AB  - The new millennium was manifested by principally new demographic situation
      characterized by an increase in the proportion of elderly population in the total
      population of the world and the spread of chronic non-communicable diseases.
      These changes have led to increased demand for health services, including safe
      and effective medicines. Creation of mechanisms ensuring international security
      of medicines circulation requires formation of an effective foreign policy and
      the reform of the regulatory framework at the national level, as well as
      improving the existing international and regional regulatory systems of all
      stages of the drug circulation to solve the most important challenges of the
      sector.

PMID- 25946862
TI  - Improving named entity recognition accuracy for gene and protein in biomedical
      text literature.
AB  - The task of recognising biomedical named entities in natural language documents
      called biomedical Named Entity Recognition (NER) is the focus of many researchers
      due to complex nature of such texts. This complexity includes the issues of
      character-level, word-level and word order variations. In this study, an approach
      for recognising gene and protein names that handles the above issues is proposed.
      Similar to the previous related works, our approach is based on the assumption
      that a named entity occurs within a noun group. The strength of our proposed
      approach lies on a Statistical Character-based Syntax Similarity (SCSS) algorithm
      which measures similarity between the extracted candidates and the well-known
      biomedical named entities from the GENIA V3.0 corpus. The proposed approach is
      evaluated and results are satisfied. For recognitions of both gene and protein
      names, we achieved 97.2% for precision (P), 95.2% for recall (R), and 96.1 for F
      measure. While for protein names recognition we gained 98.1% for P, 97.5% for R
      and 97.7 for F-measure.

PMID- 25946863
TI  - Identification of phage-induced genomic islands in the 13 Streptococcus pyogenes
      strains using genome barcodes.
AB  - With the revolutionary invention of the high-throughput sequencing technique, the
      production of bacterial genomes is significantly sped up. The in silico
      characterisation of genomic islands (GIs) in the pathogenic bacterium becomes
      increasingly needed, due to the time consumption and the high cost of the
      experimental techniques. A GI can be computationally detected through the DNA
      composition. Barcode, a dimension reduction and visualisation technique of
      genomic DNA composition, was recently applied to detect different DNA
      compositions effectively. In this work, we proposed a Barcode-based technique to
      detect Phage-induced Genomic Islands (PGIs) in the 13 completely sequenced
      strains of Streptococcus pyogenes. Our experimental results showed that the
      detected PGIs are highly consistent with the known GIs, the novel PGIs are
      promising candidates for the clinical diagnosis of S. pyogenes.

PMID- 25946864
TI  - Genome-wide nucleosome detection based on the dinucleotide position frequencies.
AB  - It has been discovered that the properties of nucleosome-bound and linker DNA
      sequences have important effects on nucleosome positioning. On the other hand,
      the position frequencies of the nucleosome-bound and linker DNA reveal most of
      their statistical properties. Therefore, two methods based on the statistical
      properties of the DNA sequences are proposed for nucleosome positioning. The
      first method defines the score profile based on the position-frequency
      differences of some dinucleotides which are most different in the nucleosome
      bound and linker DNAs. Our second method is defined by combining the differences
      in dinucleotide position frequencies and the periodicity of nucleosome-bound
      DNAs. Experiment results on Saccharomyces cerevisiae show that our second method
      outperforms significantly other algorithms in nucleosome positioning performed in
      our paper. Furthermore, this algorithm also achieves the highest accuracy and F
      score on the Simian virus 40 chromatin even if the dinucleotide position
      frequency data are extracted from the S. cerevisiae.

PMID- 25946865
TI  - Automatic quantitative analysis and localisation of protein expression with GDF.
AB  - When detecting the difference of protein expression between normal and cancerous
      tissues, the shape measurement of protein mostly depends on semi-automatic
      analysis of image software, which makes the results vulnerable to subjective
      factors. In this paper, GDF (generalised data field) is proposed to discover
      protein expression region and further locate it by taking cell nucleus as a
      reference. Based on the potential distribution, pixels of the image are firstly
      divided into different clusters. Each cluster represents protein expression in a
      different degree to precisely describe the details. Then, the clusters are merged
      into two groups under the requirements of experts or users. Meanwhile, the shapes
      of cell nuclei are measured, which favours the localisation of the protein
      expression. Compared with KM and EM, experimental results demonstrate that by
      using GDF, the protein can be extracted from an image easily and objectively, and
      the noises of background are further eliminated.

PMID- 25946866
TI  - A hybrid named entity tagger for tagging human proteins/genes.
AB  - The predominant step and pre-requisite in the analysis of scientific literature
      is the extraction of gene/protein names in biomedical texts. Though many taggers
      are available for this Named Entity Recognition (NER) task, we found none of them
      achieve a good state-of-art tagging for human genes/proteins. As most of the
      current text mining research is related to human literature, a good tagger to
      precisely tag human genes and proteins is highly desirable. In this paper, we
      propose a new hybrid approach based on (a) machine learning algorithm
      (conditional random fields), (b) set of (manually constructed) rules, and (c) a
      novel abbreviation identification algorithm to surmount the common errors
      observed in available taggers to tag human genes/proteins. Experiment results on
      JNLPBA2004 corpus show that our domain specific approach achieves a high
      precision of 80.47, F-score of 75.77 and outperforms most of the state-of-the-art
      systems. However, the recall of 71.60 still remains low and leaves much room for
      future improvement.

PMID- 25946867
TI  - The linked human imprintome v1.0: over 120 genes confirmed as imprinted impose a
      major review on previous censuses.
AB  - The whole set of human imprinted genes, termed imprintome, is here analysed by
      means of a reasonable, valid application of the Semantic Web and Linked Data
      approaches to a few structured datasets in order to provide a comprehensive
      collection of imprinted genes in the human genome. Thus, we have stored,
      organised, filtered, and analysed massive amounts of existing data on human
      imprinted genes towards compiling, structuring and linking data to comprise a
      sharing resource for genome and epigenome interrogated studies. Our datasets of
      linked data are the actual research outcome of this human imprintome analysis
      because as genomics become more and more data intensive, due to huge amounts of
      biological data, so does our needs for more structured data to be easier mined
      and shared. We present the resulting first version of the Linked Human Imprintome
      as a project within Linked Open Data (LOD) initiative (http://lod-cloud.net/)
      through Data Hub (http:// thedatahub.org/en/dataset/a-draft-version-of-the-linked
      human-imprintome).

PMID- 25946868
TI  - [Soft tissue rheumatic disorders: important for general practice].

PMID- 25946869
TI  - [Greater trochanteric pain syndrome].
AB  - Trochanteric bursitis, also known as "greater trochanter pain syndrome", is a
      frequent and often under-diagnosed cause of pain in the lateral hip region. The
      diagnosis is essentially based on the clinical examination; however various forms
      of imaging may be useful to confirm the diagnosis and particularly to ex- clude
      other aetiologies. The different therapeutic options include non-steroidal anti
      inflammatories, physiotherapy, local injections of cortisone and local
      anaesthetic, and extra-corporeal shock wave therapy. Surgical intervention is
      only indicated in rare cases.

PMID- 25946870
TI  - [Elbow tendinopathy].
AB  - The lateral and medial epicondylitis is often manifested in a professional or in
      a sport context leading to repetitive wrist movements. The diagnosis is primarily
      clinical. Additional tests are indicated in chronic evolution and in searching
      for differential diagnoses. Elbow X-ray can be completed with ultrasound or MRI,
      the most efficient but expensive diagnostic procedure. There is no consensus on
      treatment. After a period of rest, stretching then strengthening exercises are
      recommended. Corticosteroid injections may provide a short-term beneficial
      effect. Platelet-Rich Plasma injections have recently gained notoriety. In case
      of failure of treatment, surgery is possible, but only in a minority of patients.

PMID- 25946871
TI  - [Tendinitis in athletes: etiology, diagnosis and treatment].
AB  - Tendinopathy is one of the most common diagnosis in sports. Knowledges about
      their etiology, the repair process to their diagnosis and their treatment have
      improved thanks to the development of imaging, especially ultra- sound. The
      disorder whose etiology could be mechanical or degenerative can cause long- term
      disability and sometimes the end of the sport carreer. The risk of reccurence is
      com- mon; this may lead to tendon rupture whose functional effects can be
      significative. The management should be early: it must respect the deadlines for
      tendon healing and pro- pose a gradual recovery efforts after elimina tion of the
      contributing factors involved.

PMID- 25946872
TI  - [Achilles tendinopathy].
AB  - Achilles tendinopathy (AT) is the most common cause of posterior heel pain. It is
      most often due to mechanical stress related to overload or overuse of muscle
      tendon unit. It also may be associated in a minority of cases with inflammatory
      arthritis. Pain secondary to AT is generally located in the corporeal part of the
      tendon or its attachment to the bone and is worsened by exercise. Examination can
      reveal a painful swelling or thickening on palpation. Additional tests are not
      routinely recommended but may be useful. Treatment should be tailored to the
      stage of tendinopathy and to functional disability, and should include an
      assessment of predisposing factors, analgesia and physiotherapy. Other treatments
      (shock waves, ultrasound) are less well documented. The indications and
      effectiveness of infiltrations are controversial and are reserved for chronic AT.
      The risk benefit ratio should be well discussed with the patient.

PMID- 25946873
TI  - [Musculoskeletal ultrasound in the management of tendinopathy].
AB  - Musculoskeletal ultrasound (US) appears to be a major tool for the management of
      tendi- nopathy because of its accessibility and re- liability. For example,
      except for partial tears, experts agree to consider US as reliable as MRI for the
      diagnosis of rotator cuff disorders. US may also be useful in confirmation of epi
      condylitis of unusual clinical presentation, re- vealing sometimes tendon tears
      or lesion of the lateral collateral ligament. Moreover, joint disease or nerve
      compression may be de- monstrated. However, there is no US finding which is
      specific of inflammatory or mechani- cal diseases. US needs to be integrated in
      the clinical context.

PMID- 25946874
TI  - [Extension of mobile team services to the home: pilot project in the Vaud
      canton].
AB  - The main objective of this project about mobile team service extension to the
      socio-educational home of the whole Vaud canton targets to decompartmentalize the
      socio-educational and youth-psychiatry domains. 64 patient were assessed during
      this pilot phase (after one-year functioning). In addition, a satisfaction survey
      was done either at the end of the follow up or at the end of the pilot phase of
      the project (31.12.2012). This experience was very positive as highlighted by the
      vast majority of the person involved in the socio-educational and youth
      psychiatric domains taking care of youth. A desire of extension of mobile team
      service to other institutional structure or other situations was expressed.

PMID- 25946875
TI  - [Complexity and uncertainty].

PMID- 25946876
TI  - [Should pre-exposure prophylaxis be used to prevent HIV?].

PMID- 25946877
TI  - [2015: for or against non-invasive trisomy 21 screening?].

PMID- 25946878
TI  - [Including corticoids in the treatment of community-acquired pneumonia?].

PMID- 25946879
TI  - [Sleep or hang in the prisons of France].

PMID- 25946880
TI  - [The states refuse to separate basic from supplementary insurance].

PMID- 25946881
TI  - [Transplantation: the National refuses presumed consent].

PMID- 25946882
TI  - [False science against disturbing truth].

PMID- 25946883
TI  - Mining gene-centric relationships from literature: the roles of gene mutation and
      gene expression in supporting drug discovery.
AB  - Identifying drug target candidates is an important task for early development
      throughout the drug discovery process. This process is supported by the
      development of new high-throughput technologies that enable better understanding
      of disease mechanism. It becomes critical to facilitate effective analysis of the
      large amount of biological data. However, with much of the biological knowledge
      represented in the literature in the form of natural text, analysis and
      interpretation of high-throughput data has not reached its potential
      effectiveness. In this paper, we describe our solution in employing text mining
      as a technique in finding scientific information for target and biomarker
      discovery from the biomedical literature. Our approach utilises natural language
      processing techniques to capture linguistic patterns for the extraction of
      biological knowledge from text. Additionally, we discuss how the extracted
      knowledge is used for the analysis of biological data such as next-generation
      sequencing and gene expression data.

PMID- 25946884
TI  - Margin-maximised redundancy-minimised SVM-RFE for diagnostic classification of
      mammograms.
AB  - Classification techniques function as a main component in digital mammography for
      breast cancer treatment. While many classification techniques currently exist,
      recent developments in the derivatives of Support Vector Machines (SVM) with
      feature selection have shown to yield superior classification accuracy rates in
      comparison with other competing techniques. In this paper, we propose a new
      classification technique that is derived from SVM in which margin is maximised
      and redundancy is minimised during the feature selection process. We have
      conducted experiments on the largest publicly available data set of mammograms.
      The empirical results indicate that our proposed classification technique
      performs superior to other previously proposed SVM-based techniques.

PMID- 25946885
TI  - Molecular phylogeny analysis using correlation distance and spectral distance.
AB  - A wide range of methods with or without sequence alignment have been used to
      study molecular phylogeny for information on the evolution of species. Two
      approaches to construct the phylogenetic tree using (a) direct correlation of
      protein sequences and (b) difference between the Discrete Fourier Transform
      coefficients are described. The proposed methods use a transformation where each
      amino acid is represented by its Electron-Ion Interaction Potential (EIIP) value.
      Phylogenetic tree of two mammalian orders, primates and cetacea, is generated
      based on Fitch-Margoliash, Neighbour-Joining and UPGMA methods and compared. The
      phylogenetic tree of evolutionary relationships thus obtained can be used for
      comparison of species and gene sequences. The information thus gathered provide
      meaningful insights into the pattern and process of evolution which will help
      researchers in developing new breeds of animals and plants.

PMID- 25946886
TI  - A mobile system for real-time context-aware monitoring of patients' health and
      fainting.
AB  - Patient context awareness is an important concept for application services in
      mHealth environments. In this paper we present a multi-sensors system that uses a
      rule-based DSS able to enhance the accuracy of potentially dangerous heart rate
      variability by taking into account patient context information. In addition the
      proposed system is able to detect also patient falls in real time. We have
      designed and implemented an intelligent, user-friendly, and context-aware system
      that allows receiving data from several sensors and provides the computational
      power for context recognition. We also show that the use of an intelligent
      approach relying on a rule-based DSS for the analysis of data and vital signs is
      better than approaches missing either DSS or context-awareness. Finally, the
      paper also describes a case study where the system has revealed important
      benefits for both patients and medical staff.

PMID- 25946887
TI  - An improved differential evolution algorithm for enhancing biochemical pathways
      simulation and production.
AB  - This paper presents an Improved Differential Evolution (IDE) algorithm to improve
      the kinetic parameter estimation in simulating the glycolysis pathway and the
      threonine biosynthesis pathway. Experimentally derived time series kinetic data
      are noisy and possess many unknown parameters. These characteristics of kinetic
      data cause lengthy computational time to compute the optimum value of the kinetic
      parameters. To solve this problem, this study had been conducted to develop a
      hybrid method that combined the Differential Evolution algorithm (DE) and the
      Kalman Filter (KF) to produce IDE. Results have shown that lesser computation
      time (6% and 18.5% faster) and more robust to noisy data with significant reduced
      error rates (93% and 79% reduced error rates) compared with the Genetic Algorithm
      (GA) and DE, respectively, in glycolysis and threonine biosynthesis pathway
      simulations. IDE is reliable as it demonstrated consistent standard deviation
      values which were close to mean values. We foresee the applicability of IDE into
      other metabolic pathway simulations.

PMID- 25946888
TI  - A new feature selection method for computational prediction of type III secreted
      effectors.
AB  - The type III secretion system (T3SS) is a specialised protein delivery system
      that plays an important role in pathogenic bacteria. However, the secretion
      mechanism has not been fully understood yet. Especially, the identification of
      type III secreted effectors is a notoriously challenging problem which has
      attracted a lot of research interests in recent years. In this paper, we
      introduce a machine learning method using amino acid sequence features for
      predicting T3SEs. We use a topic model called HMM-LDA to select useful features,
      and conduct experiments on Pseudomonas syringae as well as some other bacterial
      genomes. The cross-validation results on P. syringae data set show an improved
      prediction accuracy with the reduced feature set. The experimental results on the
      test sets also demonstrate that the accuracy of the proposed method is comparable
      to or better than the accuracies achieved by other available T3SE prediction
      tools.

PMID- 25946889
TI  - A comprehensive analysis about the influence of low-level preprocessing
      techniques on mass spectrometry data for sample classification.
AB  - Matrix-Assisted Laser Desorption Ionisation Time-of-Flight (MALDI-TOF) is one of
      the high-throughput mass spectrometry technologies able to produce data requiring
      an extensive preprocessing before subsequent analyses. In this context, several
      low-level preprocessing techniques have been successfully developed for different
      tasks, including baseline correction, smoothing, normalisation, peak detection
      and peak alignment. In this work, we present a systematic comparison of different
      software packages aiding in the compulsory preprocessing of MALDI-TOF data. In
      order to guarantee the validity of our study, we test multiple configurations of
      each preprocessing technique that are subsequently used to train a set of
      classifiers whose performance (kappa and accuracy) provide us accurate
      information for the final comparison. Results from experiments show the real
      impact of preprocessing techniques on classification, evidencing that
      MassSpecWavelet provides the best performance and Support Vector Machines (SVM)
      are one of the most accurate classifiers.

PMID- 25946890
TI  - SGR, regulatory issues and GME among topics at National Advocacy Conference.

PMID- 25946891
TI  - Making a difference through a collective voice: an interview with Sarah Sanders.

PMID- 25946892
TI  - PUL.

PMID- 25946893
TI  - Analysis of blood donor motivations.
AB  - INTRODUCTION: Blood and blood products are essential medical treatments for all
      age groups. The primary source for blood products in the U.S. is volunteer
      donors. Thus, donor recruitment and donor retention are vital factors for a blood
      bank to maintain its supply. We proposed that developing a better understanding
      of donors' motivations to donate would improve a blood bank's ability to secure a
      more robust supply of blood. METHODS: Individuals ages 18-36 were approached to
      participate in the study during their blood donation appointment by completing a
      questionnaire. SAS software was used to statistically analyze the responses.
      Univariate analysis was done using Fisher's exact test. A multivariate model was
      constructed controlling for age and marital status, including the variables that
      were significant in univariate analysis. RESULTS: No individual motivating or
      inhibiting factor reached statistical significance. The odds ratio for subsequent
      donation for donors with 10-plus donations versus those with one to three
      donations was 4.296 (p-value 0.004). The odds ratio regarding donors' likelihood
      of returning to donate for those donating within three to six months versus 1
      plus year was 4.806 (p-value < 0.001). No employer was found to discourage blood
      donations. CONCLUSIONS: Although no individual factors were found to be
      statistically significant, the identification of optimal time intervals and total
      number of donations at which donors are more likely to return may allow for more
      strategic scheduling of blood drives, increasing the likelihood of a donor
      returning while also increasing the total number of donations for that
      individual.

PMID- 25946894
TI  - Stress fracture of the hook of the hamate: a case report.
AB  - Hook of the hamate fractures are uncommon. This fracture is usually seen in
      sports involving a club or a racquet (i.e., baseball or golf) and is caused by
      blunt trauma. Stress fractures of the hamate are exceedingly rare. Because of its
      subcutaneous position and associated soft tissue structures, hook of the hamate
      fractures can be difficult to diagnosis. When treated early, conservative (non
      operative) options can be used to successfully treat the fracture. When the
      diagnosis is delayed, nonunion of the fracture is common and is usually treated
      with surgery. This case represents a hook of the hamate stress fracture that
      healed with casting in spite of being seen two months from the onset of symptoms.
      Hamate fractures are reviewed, including the anatomy and treatment options for
      hook of the hamate fractures.

PMID- 25946895
TI  - Pregnancy of unknown location.
AB  - The development of highly sensitive and accurate human chorionic gonadotropin
      assays as well as the improvement of vaginal ultrasound have allowed for the
      early detection of pregnancy and have reduced the morbidity and mortality
      associated with ectopic gestations. One of the byproducts of this increased
      sensitivity is pregnancy of unknown location (PUL), a term which is used to
      describe pregnancy in a woman with a positive pregnancy test but no signs of
      intrauterine or extrauterine pregnancy. A PUL can include an early intrauterine
      pregnancy, a failing intrauterine/extrauterine pregnancy or ectopic pregnancy.
      Modern medical management has improved the diagnosis and treatment of early
      pregnancy and pregnancy loss. In the hemodynamically stable patient with PUL,
      expectant management has been shown to be safe and allows for confirmatory
      studies before proceeding with therapy.

PMID- 25946896
TI  - Emerging inhalers in the management of COPD.

PMID- 25946897
TI  - DAKOTACARE update: "choosing wisely"-- what our peers tell us about quality.

PMID- 25946898
TI  - Patient education. How to prevent early aging.

PMID- 25946899
TI  - Chinese patients with major depression: Do concomitant pain symptoms affect
      quality of life independently of severity of depression?
AB  - OBJECTIVE: This study investigated whether painful physical symptoms (PPSs)
      influenced quality of life (QoL) when adjusting for severity of depression.
      METHODS: Severity of depression, QoL and PPSs were assessed at baseline and 3
      months among the Chinese cohort (n = 300) of a 3-month observational study of
      major depressive disorder (MDD) in East Asia. The presence of PPS was defined as
      'a mean score of >=2 on the Somatic Symptom Inventory pain-related items'.
      Regression analyses determined predictors of QoL at 3 months, adjusting for age,
      sex, depressive symptoms, overall severity and QoL at baseline. RESULTS: PPSs
      were present (PPS+) at baseline in 35.3% of patients. Over 3 months, in the whole
      sample, EuroQoL visual analogue scale (EQ-VAS) score improved from 45.5 (standard
      deviation [SD]: 20.9) to 81 (SD: 16.7), and EuroQoL 5-Dimension Questionnaire (EQ
      5D) score improved from 0.52 (SD: 0.31) to 0.89 (0.16). At 3 months, mean EQ-VAS
      was 75.9 (SD: 17.7) for PPS+ versus 83.7 (SD: 15.6) for PPS-, and mean EQ-5D was
      0.83 (SD: 0.17) versus 0.92 (SD: 0.14). PPS+ at baseline was a significant
      predictor of QoL at 3 months after adjusting for socio-demographic and baseline
      clinical variables. CONCLUSIONS: PPSs were associated with less improvement in
      QoL in patients receiving treatment for MDD, independent of severity of
      depression.

PMID- 25946901
TI  - Chimeric antigen receptor T cells: power tools to wipe out leukemia and lymphoma.
AB  - Adoptive cell therapy for malignant diseases is showing promise in recent early
      phase trials in the treatment of B cell leukemia/lymphoma. Genetically engineered
      with a tumor-specific chimeric antigen receptor, patient's T cells produce
      lasting and complete leukemia regression. However, treatment is associated with
      some toxicity which needs our attention and the field still faces some hurdles at
      the scientific, technologic and clinical levels. Surmounting these obstacles will
      establish chimeric antigen receptor T cell therapy as a powerful approach to cure
      hematologic malignancies, paving the way for the treatment of other common types
      of cancer in the future. 

PMID- 25946900
TI  - Residue-Based Preorganization of BH3-Derived alpha/beta-Peptides: Modulating
      Affinity, Selectivity and Proteolytic Susceptibility in alpha-Helix Mimics.
AB  - We report progress toward a general strategy for mimicking the recognition
      properties of specific alpha-helices within natural proteins through the use of
      oligomers that are less susceptible than conventional peptides to proteolysis.
      The oligomers contain both alpha- and beta-amino acid residues, with the density
      of the beta subunits low enough that an alpha-helix-like conformation can be
      adopted but high enough to interfere with protease activity. Previous studies
      with a different protein-recognition system that suggested ring-constrained beta
      residues can be superior to flexible beta residues in terms of maximizing
      alpha/beta-peptide affinity for a targeted protein surface. Here, we use mimicry
      of the 18-residue Bim BH3 domain to expand the scope of this strategy. Two
      significant advances have been achieved. First, we have developed and validated a
      new ring-constrained beta residue that bears an acidic side chain, which
      complements previously known analogues that are either hydrophobic or basic.
      Second, we have discovered that placing cyclic beta residues at sites that make
      direct contact with partner proteins can lead to substantial discrimination
      between structurally homologous binding partners, the proteins Bcl-xL and Mcl-1.
      Overall, this study helps to establish that alpha/beta-peptides containing ring
      preorganized beta residues can reliably provide proteolytically resistant ligands
      for proteins that naturally evolved to recognize alpha-helical partners.

PMID- 25946902
TI  - Effect of Female-Biased Sex Ratios on Female Homosexual Behavior in Japanese
      Macaques: Evidence for the "Bisexual Preference Hypothesis".
AB  - We aimed to explain the frequent and prevalent female homosexual behavior in the
      context of female-biased operational sex ratios (OSR) and qualified sex ratios
      (Q) in a free-ranging group of Japanese macaques (Macaca fuscata) living at
      Arashiyama-Kyoto, Japan. Our data included the average availability of sexually
      mature males during females' putative fertile period (OSR), the ratio of sexually
      mature males to sexually mature females (Q), as well as heterosexual and female
      homosexual solicitations and consortships collected during 13 mating seasons from
      136 females. Our results did not support the "heterosexual deprivation
      hypothesis," which holds that female homosexual behavior is attributable to a
      shortage of male mates. Likewise, our results did not support the "lack of
      opposite-sex sexual competitor hypothesis," which holds that females have more
      access to female mates when male sexual rivals are scarce. Of the 11 predictions
      tested, only one yielded statistically significant results: we found that higher
      ratios of availability of preferred female partners to preferred male partners
      were associated with female homosexual consortships rather than female
      heterosexual consortships. This result supported the "bisexual preference
      hypothesis," which holds that female homosexual behavior is attributable to
      female preference for certain female mates relative to certain male mates. We
      conclude that when a female targets another female as a mate, it is an active
      choice for a female sexual partner over available male alternatives, rather than
      a by-default situation that occurs because males are not available as sexual
      partners, or because females are better able to access female sexual partners due
      to a scarcity of male sexual competitors. 

PMID- 25946903
TI  - Gender Atypicality and Anxiety Response to Social Interaction Stress in
      Homosexual and Heterosexual Men.
AB  - Gender non-conforming behavior and a homosexual sexual orientation have both been
      linked to higher levels of anxiety. This study examined the independent and
      interactive effects of gender atypicality and sexual orientation on levels of
      state anxiety immediately following a stressful social interaction task among a
      sample of homosexual and heterosexual Israeli men (n = 36). Gender atypicality
      was measured via both self-report and observer ratings. State anxiety was
      measured via both self-report immediately subsequent to the stressful social
      interaction task and pre- to post task changes in salivary cortisol. Results
      showed that self-reported gender atypicality and heterosexual sexual orientation
      predicted higher levels of self-reported social interaction anxiety, but not
      changes in cortisol. There were no sexual orientation by gender behavior
      interactions and there were no significant effects for observer rated gender
      atypicality. These findings suggest that gender atypicality, not homosexuality,
      place individuals at risk for increased anxiety.

PMID- 25946904
TI  - Becoming Gay? Immigration Policies and the Truth of Sexual Identity.
AB  - Our article is about the new relevance of the category of "the homosexual" in
      immigration policies. This novelty is paradoxical: while homosexuality had
      previously been defined exclusively in negative terms, from the point of view of
      the State, it has now assumed a positive value in the West--since it can be
      invoked to justify asylum seeking. The argument has two prongs. On the one hand,
      taking homosexuality into account for immigration control implies a definition of
      gay identity. On the other, the objects of these policies are also subjects:
      their own identity is caught up in this transnational process of identification.
      Fieldwork for this article was conducted in France on bi-national same-sex
      couples. However, the new categorization of homosexuality extends far beyond--in
      Europe and throughout the world. We argue that the politics of identity are not
      just, and not primarily about identity politics; they have to do both with
      politics in general and policies in particular.

PMID- 25946905
TI  - Inclusion complexes of bendamustine with beta-CD, HP-beta-CD and Epi-beta-CD: in
      vitro and in-vivo evaluation.
AB  - The objective of the present work was to investigate the inclusion behavior of
      bendamustine (BM) with beta-cyclodextrin and its hydrophilic derivatives (HP-beta
      CD and Epi-beta-CD) for the enhancement of aqueous solubility, dissolution and
      bioavailability. The supramolecular binary complexes were prepared by three
      different methods, viz. physical mixture (PM), kneading (KND) and co-evaporation
      (COE). Phase-solubility study revealed the higher solubilizing and complexing
      ability of polymerized cyclodextrin (Ks = 645 M(-1)) than parent cyclodextrin (Ks
      = 43 M(-1)) and chemically derived cyclodextrin (Ks = 100 M(-1)). Meanwhile, the
      solubility of BM was significantly enhanced in phosphate buffer of pH 6.8, which
      was 24.5 folds greater compared with the phosphate buffer pH 4.5 and four times
      greater than aqueous medium. The dissolution efficiency was found to be highest
      for BM: Epi-beta-CD complex (87%) compared to BM: HP-beta-CD complex (84%), BM:
      beta-CD (79%) and pure drug (20%). In-vivo pharmacokinetic study revealed that
      the bioavailability of BM was enhanced 2.55 times on complexation with Epi-beta
      CD using KND method. The t1/2 of BM was increased from 34.2 min to approximately
      75.7 min, allowing the absorption for longer time. The order of increase in
      solubility, dissolution and bioavailability of BM was KND > COE > PM > pure drug.
      Thus, the strategy of host-guest inclusion was very effective and could be
      successfully used in the development of suitable pharmaceutical dosage form with
      enhanced therapeutic activity. 

PMID- 25946906
TI  - VALIDATION OF THERAPEUTIC RESPONSE ASSESSMENT BY BONE SCINTIGRAPHY IN PATIENTS
      WITH BONE-ONLY METASTATIC BREAST CANCERS DURING ZOLEDRONIC ACID TREATMENT:
      COMPARISON WITH COMPUTED TOMOGRAPHY ASSESSMENT.
AB  - PURPOSE: To validate the use of bone scintigraphy (BS) versus computed tomography
      (CT) for therapeutic monitoring in patients during treatment with zoledronic
      acid. MATERIALS AND METHODS: Eleven patients with bone-only metastatic disease
      and being treated with zoledronic acid were included. The effects of therapies
      including chemotherapy and hormone therapy were evaluated in 25 separate
      examinations in total as follows: complete response (CR), when no bone metastasis
      was visible; partial response (PR), when a decrease in the lesion area was
      detected; stable disease (SD), when no or slight change was observed; and
      progressive disease (PD), when new or enlarged lesion areas were observed.
      RESULTS: The accuracies of examination by Readers 1, 2, and 3 respectively were
      76%, 80% and 76% for BS, 52%, 48%, and 40% for CT, and 64%, 52% and 60% for BS
      and CT combined with Readers 2 and 3 observing significant differences between CT
      and BS results. The rates of interobserver agreement between Readers 1 and 2,
      between Readers 1 and 3, and between Reader 2 and 3 respectively, were 84%, 80%
      and 88% (kappa = 0.648, 0.561 and 0.766) for BS, 52%, 56%, and 60% (kappa =
      0.180, 0.278 and 0.282) for CT, and 52%, 60%, and 56% (kappa = 0.215, 0.282 and
      0.232) for CT and BS combined. CONCLUSION: BS is effective for assessing the
      response of bone metastasis to therapy in patients during zoledronic acid
      treatment.

PMID- 25946907
TI  - THE EFFECT OF OBESITY ON DOSE OF DEXMEDETOMIDINE WHEN ADMINISTERED WITH FENTANYL
      DURING POSTOPERATIVE MECHANICAL VENTILATION--RETROSPECTIVE.
AB  - We carried out a retrospective investigation on the effect of obesity on
      dexmedetomidine (DEX) requirements when administered with fentanyl (FEN) during
      mechanical ventilation after major surgeries. After Institutional Review Board
      approval, 14 obese patients with a body mass index (BMI) >= 30 kg/m(2) and the
      same number of non-obese patients with similar backgrounds to the obese patients
      were selected from medical records. Doses of DEX in the first 48 h or until the
      end of sedation or extubation were calculated for comparison. In addition to
      comparison of dosing between the groups, associations between total body weight
      (TBW), BMI, and lean body mass (LBM) values and doses of DEX (mcg/h), between BMI
      and various indices (i.e., amount per TBW per hour and amount per LBM per hour)
      of DEX doses, and between above indices of DEX and FEN doses were also examined.
      There were no significant differences in DEX dose indices between the groups.
      However, DEX requirements (mcg/h) were significantly increased with TBW (kg) (r =
      0.51, P = 0.003), BMI (r = 0.49, P = 0.006) and LBM (kg) (r = 0.42, P = 0.02),
      which might have enhanced the DEX metabolism with physiological changes with
      obesity. These findings will be beneficial for future clinical pharmacological
      analysis of DEX. 

PMID- 25946908
TI  - BRAIN HYPOTHERMIA THERAPY FOR NEONATAL HYPOXIC-ISCHEMIC ENCEPHALOPATHY WITH A
      SEVERELY ELEVATED SERUM CREATINE KINASE LEVEL.
AB  - Several studies have shown that brain hypothermia therapy (BHT) after neonatal
      hypoxic-ischemic encephalopathy (HIE) can improve neurodevelopmental outcomes.
      However, there have been no reports of the neurodevelopmental outcomes for the
      infant with a serum creatine kinase (CK) level above 20,000 IU/L in association
      with neonatal HIE. We report a female infant with a very high serum CK level
      (26,428 IU/L) associated with neonatal asphyxia. We diagnosed this infant with
      moderate HIE, and BHT was achieved by head cooling within 6 hours after birth to
      an esophageal temperature of 34.5 degrees C. There were no significant adverse
      events during BHT, and the CK level spontaneously decreased. Although we report
      only the short-term outcomes for this case, she presents neurodevelopmental
      delays at the age of 18 months. It may be correlated between high serum CK level
      and long-term neurodevelopmental delays.

PMID- 25946909
TI  - EARLY STAGE RESPONSES OF INTENSIVE CARE UNITS DURING MAJOR DISASTERS: FROM THE
      EXPERIENCES OF THE GREAT EAST JAPAN EARTHQUAKE.
AB  - The present study investigated the role of intensive care units (ICU) during
      disasters, including the responses of our ICU following the Great East Japan
      Earthquake on March 11, 2011. Our ICU comprises 8 beds for postoperative
      inpatients and those with rapidly deteriorating conditions; 20 beds in an
      emergency unit for critically ill patients; and 17 beds for neonates. It is
      important to secure empty beds when a major disaster occurs, as was the case
      after the Great Hanshin Earthquake, due to the resulting large numbers of trauma
      patients. Therefore, each ICU section cooperated to ensure sufficient space for
      admissions following the Great East Japan Earthquake. However, unlike the Great
      Hanshin Earthquake, securing beds was ultimately unnecessary due to the nature of
      the recent disaster, which also consisted of a subsequent tsunami and nuclear
      accident. Therefore, air quality monitoring was required on this occasion due to
      the risk of environmental radioactive pollution from the nuclear disaster causing
      problems with artificial respiration management involving atmospheric air. The
      variability in damage arising during different disasters thus requires a flexible
      response from ICUs that handle seriously ill patients. 

PMID- 25946910
TI  - A Feminine Care Clinical Research Program Transforms Women's Lives.
AB  - Feminine hygiene products and menstruation education have transformed the lives
      of women throughout the world. The P&G Feminine Care Clinical Innovation Research
      Program has played a key role by expanding scientific knowledge as well as
      developing technical insights and tools for the development of feminine hygiene
      products. The aim has been to meet the needs of women throughout their life
      stages, advancing their urogenital health beyond just menstruation, as well as
      helping to understand the role of sex hormones in various important health issues
      that women face. This review article highlights key contributions and research
      findings in female hygiene products, urogenital health research, and method
      development. The clinical research team focused on utilizing the results of
      clinical safety studies to advance the acceptance of feminine hygiene products
      world-wide. Key findings include that perception of skin sensitivity is not
      limited to the facial area, but is also relevant to the body and the genital
      area. Also, they shed light on the role of estrogen in autoimmune diseases as
      well as premenstrual syndrome. Efforts in the method development area focused on
      innovative tools that are reliable, predictive of clinical trial results and
      capable of measuring wear comfort, genital skin health, and the impact of product
      use on the consumer's quality of life. A novel method, behind-the-knee (BTK)
      test, developed to model irritation under normal wear conditions, was the first
      to account for both chemical and mechanical sources of irritation. The method has
      been accepted by the FDA as a substitute in clinical trials in some cases, and by
      American Society for Testing and Materials as a global standard test method.
      Additional proprietary methods were developed to enhance visual grading of
      irritation using cross-polarized light, to measure the amount of lotion
      transferred from sanitary pads, and to evaluate the skin mildness. Finally, the
      Farage Quality of Life tool was created to measure consumer's well-being. Based
      on the results of this extensive clinical research and the newly developed
      testing methods, the changing needs of women throughout their life stages are
      better met. 

PMID- 25946911
TI  - Research on relationship among internet-addiction, personality traits and mental
      health of urban left-behind children.
AB  - AIM: In this research, we attempted at exploring the relationships among urban
      left-behind children's internet-addiction, personality traits and mental health.
      METHODS: In the form of three relevant questionnaires (Adolescent Pathological
      Internet Use Scale, Eysenck Personality Questionnaire, Children's Edition in
      Chinese and Mental Health Test), 796 urban left-behind children in China were
      investigated, concerning internet-addiction, personality traits and mental
      health. RESULTS: (1) The internet-addiction rate of urban left-behind children in
      China reached 10.8%-a relatively high figure, with the rate among males higher
      than that among females. In terms of internet-addition salience, the figure of
      urban left-behind children was obviously higher than that of non-left-behind
      children. (2) In China, the personality deviation rate of the overall left-behind
      children was 15.36%; while the personality deviation rate of the internet
      addicted urban left-behind children was 38.88%, a figure prominently higher than
      that of the non-addicted urban left-behind children group, with the rate among
      females higher than that among males. (3) The mental health problem rate of the
      overall urban left-behind children in China was 8.43%; while the rate of the
      internet-addicted urban left-behind children was 27.77%, a figure significantly
      higher than that of the non-addicted urban left-behind children. (4) There were
      significant relationships among internet-addiction, personality traits and mental
      health. The total score of internet-addiction and its related dimensions can
      serve as indicators of personality neuroticism, psychoticism and the total scores
      of mental health.

PMID- 25946912
TI  - Health care utilization and expenditures in persons receiving social assistance
      in 2012: evidence from Switzerland.
AB  - INTRODUCTION: Lower socioeconomic position and measures of social and material
      deprivation are associated with morbidity and mortality. These inequalities in
      health among groups of various statuses remain one of the main challenges for
      public health. The aim of the study was to investigate differences in health care
      use and costs between recipients of social assistance and non-recipients aged 65
      years and younger within the Swiss healthcare system. METHODS: We analyzed claims
      data of 13 492 individuals living in Bern, Switzerland of which 391 received
      social assistance. For the year 2012, we compared the number of physician visits,
      hospitalizations, prescribed drugs, and total health care costs as covered by
      mandatory health insurance. Linear and logistic adjusted regression analyses were
      made to estimate the effect of receipt of social assistance on health service use
      and costs. RESULTS: Multivariate linear regression analysis revealed that health
      care costs increased on average by 1 666 CHF if individuals received social
      assistance. Recipients of social assistance had on average 1.2 more ambulatory
      consultations than non-recipients and got 1.65 more different medications
      prescribed as compared to non-recipients. The chance for recipients of social
      assistance to be hospitalized was almost twice that of non-recipients (Odds Ratio
      1.96, 95% confidence interval 1.49-2.59). CONCLUSIONS: Recipients of social
      assistance demonstrate an exceedingly high use of health services. The need for
      interventions to alleviate the identified inequalities in health and health care
      needs is obvious.

PMID- 25946913
TI  - Emolabeling effectively reduces the influence of ambiguous labeling on food
      packages among grocery store shoppers.
AB  - Despite increased regulations and policy enforcement for nutrition labeling,
      ambiguous labels on food items can still have deleterious effects on consumer
      perceptions of health. The present study used a counterbalanced within-subjects
      design to test if emolabeling - the use of emoticons to convey health information
      (happy = healthy; sad = not healthy) - will reduce the effects of ambiguous
      labels on consumer perceptions of the healthfulness of a food item. 85 grocery
      store shoppers were shown nutrition labels for a low calorie (LC) and a high
      calorie (HC) food with/without emolabels, and with an ambiguous label that either
      implied the food was healthy or unhealthy. Results showed that emolabels reduced
      the effectiveness of ambiguous labels: consumers rated the LC food as healthier
      and the HC food as less healthy when emolabels were added. The results suggest
      that, if implemented, this image-based emolabeling system could possibly be an
      effective buffer against the use of ambiguous labeling by food manufacturers.

PMID- 25946914
TI  - Predictors of illicit drug/s use among university students in Northern Ireland,
      Wales and England.
AB  - INTRODUCTION: The use of illicit drug/s among university students is a public
      health concern. Nevertheless, many UK studies investigated a narrow spectrum of
      variables to explore their association/s with illicit drug/s use. METHODS: We
      assessed the associations between a wide range of socio-demographic, health and
      wellbeing variables (independent variables) and having used illicit drug/s
      regularly, occasionally or never in life (dependent variables). Data (3706
      students) were collected from seven universities in England, Wales, and Northern
      Ireland, using a self-administered questionnaire. RESULTS: About 5% of the sample
      had regularly used illicit drug/s, 25% occasionally, and 70% never. Regular drug
      use (RDU) was significantly more likely among males aged 21-29 years, daily
      smokers, those with heavy episodic drinking or possible alcohol dependency (CAGE
      test), and those who perceived their academic performance better than their
      peers. RDU was less likely among students with high health awareness and those
      living with parents. The predictors of occasional drug use (ODU) were similar to
      those of RDU. However, in addition, students with higher perceived stress were
      less likely, and students who felt financial burden/s were more likely to report
      ODU, while no association with academic performance was found. Never use of
      illicit drug/s was inversely associated with most of the variables listed above,
      and was positively associated with religiosity. Illicit drug/s use goes along
      with other substance use (alcohol and smoking). The finding that illicit drug/s
      use was higher among students reporting good academic performance was surprising
      and raises the question of whether illicit drug/s may be used as performance
      enhancing drugs. CONCLUSION: The factors identified with illicit drug/s use in
      this study could be utilized to develop appropriate public health policies and
      preventive measures for the health of students. Multilevel, value based,
      comprehensive, and strategic long-term intervention plans are required. This
      could include social interventions aimed at generating recreations alternatives
      and opportunities for youth, and a critical review for current authorities'
      interventions and services. Suggestions for coping with problems of campus
      illicit drug use/abuse also need to be offered.

PMID- 25946915
TI  - Factors affecting patient satisfaction with emergency department care: an Italian
      rural hospital.
AB  - BACKGROUND: In the emergency department satisfaction is strictly linked to the
      role of the nurses, namely the first interface between patients and hospital
      services. OBJECTIVES: The purpose of the study was to identify areas of emergency
      nursing activity associated with minor or major patient satisfaction. METHODS: A
      descriptive cross-sectional study was conducted from December 2010 - May 2011, in
      the rural hospital of Orbetello, Tuscany (Italy). Convenience sampling was used
      to select patients, namely patients presenting at the emergency unit in the study
      period. The Consumer Emergency Care Satisfaction Scale was used to collect
      information on two structured subscale (Caring and Teaching). RESULTS: 259
      questionnaire were collected. Analysis indicated that only two characteristics
      significantly influenced overall satisfaction: "receiving continuous information
      from personnel about delay" positively effect (OR=7.98; p=0.022) while "waiting
      time for examination" had a negative effect (OR 0.42; p=0.026). CONCLUSIONS: The
      study was the first conduced in Italy using this instrument that enabled to
      obtain much important information about patient satisfaction with nursing care
      received in the emergency department. The results showing improvements must be
      related to educational aspects, such as explaining patients the colour waiting
      list, and communication towards patients, such as informing about emergences that
      cause queue.

PMID- 25946916
TI  - Mood changes by self-administered acupressure in Japanese college students: a
      randomized controlled trial.
AB  - The aim of this 2-week study was to examine the effects of self-administered
      acupressure intervention onlevels of mood of 54 students (34 males and 20
      females) majoring in acupuncture and moxibustion medicineat a college located in
      Fukuoka, Japan. Eligibility criteria were the ability to complete the
      intervention accurately and no history of psychiatric diseases. The students were
      randomly assigned to one of the two groups: an intervention group (IG, n = 28)
      and a control group (CG, n = 26). The IG participants completed fiveacupressure
      sessions three times a day (morning, noon, and night), involving the application
      of pressure to six acupuncture points (GB12, SI17, and LI18 according to 2008
      World Health OrganizationRegional Office in the Western Pacific standard), three
      on the left and three on the right side of the neck for 5 s each. The CG
      participants were requested to spend their time as usual. Self-reported levels of
      tension-anxiety, depression-dejection, anger-hostility, vigor, fatigue, and
      confusion over the past week were measured before and after the study as the main
      outcomes. Side effects were not predicted and not assessed. The retention rate of
      this trial was 100%. Improvements in mood, defined as a change from baseline to 2
      weeks later, were significantly greater in IG. Our results showed that self
      administered intervention had the ability to alter mood levels in college
      students. 

PMID- 25946917
TI  - Hierarchical multiple regression modelling on predictors of behavior and sexual
      practices at Takoradi Polytechnic, Ghana.
AB  - INTRODUCTION: Various psychosocial studies on health related lifestyles lay
      emphasis on the fact that the perception one has of himself as being at risk of
      HIV/AIDS infection was a necessary condition for preventive behaviors to be
      adopted. Hierarchical Multiple Regression models was used to examine the
      relationship between eight independent variables and one dependent variable to
      isolate predictors which have significant influence on behavior and sexual
      practices. METHODS: A Cross-sectional design was used for the study. Structured
      close-ended interviewer-administered questionnaire was used to collect primary
      data. Multistage stratified technique was used to sample views from 380 students
      from Takoradi Polytechnic, Ghana. A Hierarchical multiple regression model was
      used to ascertain the significance of certain predictors of sexual behavior and
      practices. RESULTS: The variables that were extracted from the multiple
      regression were; for the constant; Beta=14.202, t=2.279, p=0.023, variable is
      significant; for the marital status; Beta=0.092, t=1.996, p<0.05, variable is
      significant; for the knowledge on AIDs; Beta=0.090, t=1.996, p<0.05, variable is
      significant; for the attitude towards HIV/AIDs; =0.486, t=10.575, p<0.001,
      variable is highly significant. Thus, the best fitting model for predicting
      behavior and sexual practices was a linear combination of the constant, one's
      marital status, knowledge on HIV/AIDs and Attitude towards HIV/AIDs., Y(Behavior
      and sexual practies)= Beta0+Beta1(Marital status)+Beta2(Knowledge on HIV/AIDs
      issues)+Beta3(Attitude towards HIV/AIDs issues) Beta0, Beta1, Beta2 and Beta3 are
      respectively 14.201, 2.038, 0.148 and 0.486; the higher the better. CONCLUSIONS:
      Attitude and behavior change education on HIV/AIDs should be intensified in the
      institution so that students could adopt better lifestyles.

PMID- 25946918
TI  - The effects of case-based team learning on students' learning, self regulation
      and self direction.
AB  - INTRODUCTION: The application of the best approaches to teach adults in medical
      education is important in the process of training learners to become and remain
      effective health care providers. This research aims at designing and integrating
      two approaches, namely team teaching and case study and tries to examine the
      consequences of these approaches on learning, self regulation and self direction
      of nursing students. MATERIAL & METHODS: This is a quasi experimental study of 40
      students who were taking a course on mental health. The lessons were designed by
      using two educational techniques: short case based study and team based learning.
      Data gathering was based on two valid and reliable questionnaires: Self-Directed
      Readiness Scale (SDLRS) and the self-regulating questionnaire. Open ended
      questions were also designed for the evaluation of students' with points of view
      on educational methods. RESULTS: The Results showed an increase in the students'
      self directed learning based on their performance on the post-test. The results
      showed that the students' self-directed learning increased after the
      intervention. The mean difference before and after intervention self management
      was statistically significant (p=0.0001). Also, self-regulated learning increased
      with the mean difference after intervention (p=0.001). Other results suggested
      that case based team learning can have significant effects on increasing
      students' learning (p=0.003). CONCLUSION: This article may be of value to medical
      educators who wish to replace traditional learning with informal learning
      (student-centered-active learning), so as to enhance not only the students'
      knowledge, but also the advancement of long- life learning skills.

PMID- 25946919
TI  - Computer literacy among students of Zahedan University of Medical Sciences.
AB  - INTRODUCTION: The need for medical students to be computer literate is vital.
      With the rapid integration of information technology (IT) in the health care
      field, equipping students of medical universities withcomputer competencies to
      effectively use are needed. The purpose of this study was to assess computer
      literacy (CL) needs of medical sciences students. METHODS: This is descriptive
      analytic. The population of the study comprised all students at Zahedan
      University of Medical Sciences. 385 students from allschools (Medicine,
      dentistry, paramedics, health, rehabilitation, nursing and midwifery) were
      selected through randomized- classified sampling. For data collecting, the Lin
      Tung- Cheng questionnaire was used which it contained 24 items in six
      sections.The obtained data analyzed by SPSS 15. RESULTS: The results showed that
      the 77.1% had personal computer. The total mean of students' computer literacy
      around six domains was 141.9+/-49.5 out of 240. The most familiarity with
      computers was the ability to it in internet (29.0+/-11.4) and the lowest was
      familiarity and using ability of hard ware (17.5+/-10.6). There was a significant
      relationship between passing the Computer lesson (P=0.001), passing Computer
      course (P=0.05) and having personal computer (P=0.001) with the mean of computer
      literacy. DISCUSSION: In sum, the medical sciences students' familiarity with
      computer literacy was not satisfactory and they had not appropriate familiarity
      with computer literacy skills. The researchers suggest the officials and in
      charges to plan educational program for improving computer literacy skills in
      medical sciences students.

PMID- 25946920
TI  - Recent strategies in treatment of pulmonary arterial hypertension, a review.
AB  - Pulmonary arterial hypertension (PAH) is a disease characterized by an elevation
      in pulmonary artery pressure that can lead to right ventricular failure and
      death. The pulmonary circulation has to accommodate the entire cardiac output in
      each cardiac cycle and evolution has adapted to this by making it a low-pressure
      high-flow system. However, pathology can affect both the arterial and venous
      components of this system. Pulmonary venous hypertension mainly refers to
      diseases that result in elevated venous pressure and occurs mainly from mitral
      valve and left-sided heart disease. Standard treatment options include oral
      anticoagulation, diuretics, oxygen supplementation, and for a small percentage of
      patients, calcium channel blockers. Newer treatments include prostacyclin
      analogues, endothelin receptor antagonists, and phosphodiesterase type 5
      inhibitors. This article reviews the current treatments strategies for PAH and
      provides guidelines for its management.

PMID- 25946921
TI  - Effect of streptokinase on reperfusion after acute myocardial infarction and its
      complications: an ex-post facto study.
AB  - INTRODUCTION: Emergency treatment of patients with acute myocardial infarction is
      very important. Streptokinase in Iran is often as the only clot-busting
      medication is used. The purpose of using streptokinase medication is to revive
      the ischemic heart tissue, although has dangerous complications too. Therefore,
      the present study aimed to determine the effect of streptokinase on reperfusion
      after acute myocardial infarction and its complications, has been designed and
      conducted. MATERIALS & METHODS: This is an Ex-post facto study. The study
      population included patients who suffer from acute myocardial infarction. The
      sample size was 300 patients, and 2 groups were matched, in variables of age,
      sex, underlying disease, frequencies and area of MI. Data collection did by
      researcher making questionnaire, that accept face and content validity by 10
      expert researcher, the reliability was conducted with Spearman's test (r=0.85) by
      Test-retest method. Data analysis did by SPSS software: V 12. FINDINGS: Mean of
      EF in SK group was (46.15+/-8.11) and in control group was (43.11+/-12.57).
      Significant relationship was seen between SK, arrhythmia occurring and improve EF
      reperfusion by chi-square test (p=0.028), (p=0.020).The most arrhythmia in SK
      group was Ventricular Tachycardia (20.7%). Significant statistical relation
      between SK and mortality were found by Chi-square test (p=0.001). But a
      meaningful statistical relation was not found between SK and pulmonary edema
      incidence (p=0.071). CONCLUSIONS: Nurses of CCU should be aware about SK
      complications such as hypotension, bleeding and arrhythmias. Proposed compare SK
      and tissue plasminogen drug in reperfusion and complications effect.

PMID- 25946922
TI  - Analyzing and Prioritizing the Dimensions of Patient Safety Culture in Emergency
      Wards Using the TOPSIS Technique.
AB  - BACKGROUND & AIM: Doubtlessly, permanent development in patient care services is
      not feasible without paying attention to the culture of safety by health and
      treatment institutes. The present study is an attempt to analyze the cultural
      aspects of patient safety in the emergency wards of hospitals affiliated with the
      Tehran Medical Science University. The viewpoint of the nurses and hospital
      officials and their priorities were studied. For prioritizing the results of this
      study the TOPSIS technique was chosen. METHODS: The study was conducted as an
      analytical-descriptive and cross-sectional one. It was carried out in two parts:
      at first the cultural aspects of the patients were measured using a questionnaire
      for a six months period in 2011 in emergency wards of the hospitals under study.
      The study population was constituted of physicians and nurses of the emergency
      wards. The sample group (n=270) was selected through a cluster sampling and its
      size was determined by using the sample size formula. For data gathering, the
      standard questionnaire of Hospital Survey on Patient Safety Culture (HSOPSC) was
      used. The data were analyzed in SPSS. The aspects of the safety culture were
      prioritized using the TOPSIS model. The criteria were ranked by using the MATLAB
      software. RESULTS: There was a significant relationship among the aspects of
      performance, teamwork, feedback, mistake relationships, and the support of the
      managers (P ? 0.05). The total point of the patient safety culture in the
      majority of the hospitals were at a mean level of 3. The maximum score was 5. The
      maximum and minimum mean points were obtained by the Hasheminejad and Sina
      hospitals respectively. The results of the multivariate decision-making analysis
      indicated that human, managerial, organizational, and environmental factors were
      at the top of priorities in a descending order. The factors were extremely
      effective in the improvement of safety in hospitals. CONCLUSION: Human factors
      were the most effective and important factors in the improvement of safety in
      emergency wards. Therefore, there is a need to pay more attention to such factors
      in safety improvement programming. Training, cultural works, preparation of
      organizational environments, and motivating environmental factors were of the
      main measures that must be taken into account by the managers.

PMID- 25946923
TI  - Evaluating the Educational Environment of a Nursing School by Using the DREEM
      Inventory.
AB  - BACKGROUND: Educational Environment (EE) is considered as a key component of
      educational curriculum. AIM: The aim of this study was to evaluate the EE of
      Nursing and Midwifery School of Tehran University of Medical Sciences (TUMS) by
      using Dundee Ready Education Environment Measure (DREEM). METHODS: This cross
      sectional descriptive study was conducted in 2013. Totally, 500 nursing or
      midwifery students were recruited to the study by using the quota sampling
      method. Study data were collected by using a demographic questionnaire and the
      Persian version of DREEM questionnaire. The reliability of questionnaire was
      confirmed by Cronbach alpha which was 0.876 and 0.68-0.866 for the whole
      questionnaire and its domains, respectively. The data were analyzed by using SPSS
      v. 21.0. RESULTS: Totally, 350 completely-filled questionnaires were included in
      the final analysis. Most of the participants were nursing students (79.7%),
      female (74.6%), single (86.0%), bachelor (86.9%), first-year (36.9%), with mean
      age of 22.5 years. The mean item score of the DREEM was 2.09+/-0.49 (104.39 from
      200). Moreover, the mean item scores of the domains were as follows, perception
      of learning: 1.93+/-0.61; perception of teachers: 2.42+/-0.56; perception of
      educational atmosphere: 2.05+/-0.59; academic-self-perception: 2.06+/-0.65; and
      social-self-perception: 2.17+/-0.62. All domains were statistically significant
      except the perception of learning and educational atmosphere (p<0.001)
      CONCLUSION: Although the educational environment of the study setting was found
      to be positive, it requires improvements. Strategies such as adopting student
      centered approaches, revising the educational curriculum, strengthening student
      teacher relationship, being sensitive and responsive to students' educational
      needs, providing constructive feedback to them, and creating a comfortable,
      friendly, and supportive atmosphere can improve the educational environment.

PMID- 25946924
TI  - Evaluation of nursing students' communication abilities in clinical courses in
      hospitals.
AB  - BACKGROUND: Joint Commission on Accreditation of Healthcare Organizations (JCAHO)
      has established, improving communication as a priority for improving patient
      safety since 2006. Therefore, the present study aimed to evaluate nursing
      students' communication abilities to recognize their strengths and weaknesses in
      communication skills. METHOD: This cross-sectional study was carried out in 2014.
      The study participants included all the nursing students who passed two semesters
      in Fatemeh School of Nursing and Midwifery in Shiraz, Iran. The students'
      communication skills were assessed using a self-administered questionnaire. Then,
      the data were entered into the SPSS statistical software (v. 16) and analyzed
      using both descriptive (mean and percentage) and inferential statistics (Pearson
      correlation and ANOVA). RESULTS: Among the 200 students who completed the
      questionnaires, 58% were female and 42% were male with the mean age of 21.79
      years (SD=2.14). The results of Pearson correlation analysis demonstrated a
      significant correlation between the nursing students' clinical communication
      behavior scores and treatment communication ability scores (P<0.001). The
      findings demonstrated that most nursing students required improvement in their
      communication skills in both clinical communication behavior and treatment
      communication ability. Besides, a significant difference was observed among the
      students of different terms regarding clinical communication behaviors (P?0.05),
      but not concerning communication abilities. Nursing students in higher semesters
      had better communication skills. CONCLUSIONS: The results showed that nursing
      students in this university had a moderate ability in clinical and treatment
      communication. Thus, paying attention to standard education, curriculum revision,
      and adding some specific theoretical lessons for improving communication skills
      are mandatory during the bachelor's degree.

PMID- 25946925
TI  - Chance Constrained Input Relaxation to Congestion in Stochastic DEA. An
      Application to Iranian Hospitals.
AB  - This article developed an approached model of congestion, based on relaxed
      combination of inputs, in stochastic data envelopment analysis (SDEA) with chance
      constrained programming approaches. Classic data envelopment analysis models with
      deterministic data have been used by many authors to identify congestion and
      estimate its levels; however, data envelopment analysis with stochastic data were
      rarely used to identify congestion. This article used chance constrained
      programming approaches to replace stochastic models with "deterministic
      equivalents". This substitution leads us to non-linear problems that should be
      solved. Finally, the proposed method based on relaxed combination of inputs was
      used to identify congestion input in six Iranian hospital with one input and two
      outputs in the period of 2009 to 2012. 

PMID- 25946926
TI  - Validation of the Persian Version of the 8-Item Morisky Medication Adherence
      Scale (MMAS-8) in Iranian Hypertensive Patients.
AB  - The reliability and validity of the 8-item Morisky Medication Adherence Scale
      (MMAS-8) was assessed in a sample of Iranian hypertensive patients. In this multi
      center study which lasted from August to October 2014, a total of 200 patients
      who were suffering from hypertension (HTN) and were taking anti-hypertensive
      medication(s) were included. The cases were accessed through private and
      university health centers in the cities of Tehran, Karaj, Kermanshah, and Bafgh
      in Iran and were interviewed face-to-face by the research team. The validated
      Persian translation of the MMAS-8 was provided by the owner of this scale. This
      scale contains 7 questions with "Yes" or "No" response choices and an additional
      Likert-type question (totally 8 questions). The total score ranges from 0 to 8
      with higher scores reflecting better medication adherence. Mean (+/-SD) overall
      MMAS-8 score was 5.57 (+/-1.86). There were 108 (54%), 62 (31%), and 30 (15%)
      patients in the low, moderate, and high adherence groups. Internal consistency
      was acceptable with an overall Cronbach's ? coefficient of 0.697 and test-retest
      reliability showed good reproducibility (r= 0.940); P< 0.001. Overall score of
      the MMAS-8 was significantly correlated with systolic BP (r= - 0.306) and
      diastolic BP (r= - 0.279) with P< 0.001 for both BP measurements. The Chi-square
      test showed a significant relationship between adherence level and BP control (P=
      0.016). The sensitivity, specificity, positive predictive value (PPV), and
      negative predictive value (NPV) of the scale were 92.8%, 22.3%, 52.9%, and 76.7%,
      respectively. The Persian version of the MMAS had acceptable reliability and
      validity in Iranian hypertensive patients. This scale can be used as a standard
      and reliable tool in future studies to determine medication adherence of Persian
      speaking patients with chronic conditions. 

PMID- 25946928
TI  - Nurses' experiences of futile care at intensive care units: a phenomenological
      study.
AB  - The concept and meaning of futile care depends on the existing culture, values,
      religion, beliefs, medical achievements and emotional status of a country. We
      aimed to define the concept of futile care in the viewpoints of nurses working in
      intensive care units (ICUs). In this phenomenological study, the experiences of
      25 nurses were explored in 11 teaching hospitals affiliated to Social Security
      Organization in Ghazvin province in the northwest of Iran. Personal interviews
      and observations were used for data collection. All interviews were recorded as
      well as transcribed and codes, subthemes and themes were extracted using Van
      Manen's analysis method. Initially, 191 codes were extracted. During data
      analysis and comparison, the codes were reduced to 178. Ultimately, 9 sub-themes
      and four themes emerged: uselessness, waste of resources, torment, and aspects of
      futility.Nurses defined futile care as "useless, ineffective care giving with
      wastage of resources and torment of both patients and nurses having nursing and
      medical aspects" As nurses play a key role in managing futile care, being aware
      of their experiences in this regard could be the initial operational step for
      providing useful care as well as educational programs in ICUs. Moreover, the
      results of this study could help nursing managers adopt supportive approaches to
      reduce the amount of futile care which could in turn resolve some of the
      complications nurses face at these wards such as burnout, ethical conflicts, and
      leave. 

PMID- 25946927
TI  - Neonatal outcomes of infants admitted to a large government hospital in Amman,
      Jordan.
AB  - OBJECTIVE: To describe characteristics and outcomes of Jordanian newborns
      admitted to a large governmental neonatal intensive care unit (NICU). METHODS:
      Newborns born at the government hospital, Al Bashir, in Amman, Jordan were
      prospectively enrolled. The study focused on newborns admitted to the NICU and a
      retrospective chart review was performed. Abstraction included in-hospital
      mortality, antibiotic days, ventilation, oxygen use, and CRP levels. Rank sum and
      chi-squared tests were used to compare across outcomes. Logistic regression of
      hypothesized risk factors with death adjusted for gestational age. RESULTS: Of
      the 5,466 neonates enrolled from 2/10-2/11, medical records were available for
      321/378(84.9%) infants admitted to the NICU. The median gestational age was 36
      weeks, median birth weight was 2.3 kg, and 28(8.7%) infants died. The two most
      common reasons for admission and mortality were respiratory distress syndrome and
      prematurity. Low Apgar scores and positive CRP were predictors of mortality. Risk
      factors associated with increased use of antibiotics, oxygen hood, and mechanical
      ventilation included lower gestational age and prematurity. CONCLUSION: Infants
      admitted to the Jordanian NICU have significantly higher median gestational age
      and birth weights than in developed countries and were associated with
      significant morbidity and mortality. Continuations of global efforts to prevent
      prematurity are needed.

PMID- 25946929
TI  - Effects of Vitamin D Intake on FEV1 and COPD Exacerbation: A Randomized Clinical
      Trial Study.
AB  - AIM: This study aimed to evaluate the effects of vitamin D intake on COPD
      exacerbation and FEV1 in the patients with severe and very severe COPD. METHODS:
      This double blind placebo control randomized clinical trial study was done in the
      Ashayer university hospital in Khorramabad in 2012. Eighty eight patients with
      severe and very severe COPD were randomly selected from those who recoursed to
      the internal medicine clinic of Ashayer hospital. They were randomly allocated to
      case and placebo group. The patients received routine treatment for COPD. Along
      with the routine treatment, placebo group received 100,000 IU of oral vitamin D
      per month, for 6 months. Data was analyzed using SPSS computer software, paired t
      test, independent t-test, non parametric t-test and Pearson correlation
      coefficients. RESULTS: In each group, there were 44 patients. After the
      intervention, there were significant differences in FEV1 and the number of COPD
      exacerbation between the case and control group patients. Also, after the study,
      in the case group, FEV1 was increased and the number of COPD exacerbation was
      decreased significantly. CONCLUSION: Vitamin D intake decreased COPD exacerbation
      and improved FEV1 in the patients with severe and very severe COPD. It is
      suggested that baseline serum vitamin D levels will recorded in similar studies
      and the effect of vitamin D intake will evaluated regarding the baseline serum
      vitamin D levels.

PMID- 25946930
TI  - The readiness of postgraduate health sciences students for interprofessional
      education in iran.
AB  - AIM: Interprofessional education has been recognized as an effective educational
      approach towards enabling students to provide comprehensive and safe team care
      for promotion of health outcomes of patients. This study was conducted in order
      to assess the readiness of postgraduate health science students for
      interprofessional education/learning, as well as identify barriers to the
      implementation of such an approach in Iran from the students' point of view.
      METHODS: This was a cross-sectional and descriptive-analytical study conducted in
      2013 on 500 postgraduate students in three main professional groups: medical,
      nursing and other allied health professions across a number of Iranian
      Universities using the convenience sampling method. Quantitative Data were
      collected through self-administering the Readiness for InterProfessional Learning
      Scale (RIPLS) questionnaire with acceptable internal consistency (? = 0.86). The
      data were analyzed by SPSS18. Qualitative data were gathered by an open-ended
      questionnaire and analyzed by qualitative content analysis method. RESULTS: The
      mean score of the students' readiness (M=80, SD=8.6) was higher than the average
      score on the Scale (47.5). In comparison between groups, there was no
      statistically significant difference between groups in their readiness (p>0.05).
      Also four main categories were identified as barriers to implementation of
      interprofessional education from the students' point of view; the categories were
      an inordinately profession-oriented, individualistic culture, style of management
      and weak evidence. CONCLUSION: An acceptable degree of readiness and a generally
      favorable attitude among students towards interprofessional education show that
      there are appropriate attitudinal and motivational backgrounds for implementation
      of interprofessional education, but it is necessary to remove the barriers by
      long-term strategic planning and advancing of interprofessional education in
      order to address health challenges.

PMID- 25946932
TI  - Association Between System Reach and Exposure to Interventions and
      Characteristics of Mobile Female Sex Workers in Four High HIV Prevalence States
      in India.
AB  - Mobility among Female Sex Workers (FSWs) interrupts their demand for, and
      utilization of, health services under any intervention. Various strategic
      interventions are meant to provide access to care and reduce the incidence of HIV
      and other STIs among FSWs. This paper applies a bivariate probit regression
      analysis to explain the probability of mobile FSWs being reached by the system
      and being exposed to interventions jointly with a wide variety of characteristics
      of mobile FSWs in India. The data used are based on a cross-section survey among
      5,498 mobile FSWs in 22 districts of four high HIV prevalence states in southern
      India. A majority of mobile FSWs (59%) were street-based and about 70 percent of
      them were members of SW organization and nearly half (46%) were highly mobile.
      The majority of them (90%) had been contacted by outreach workers from any system
      in the last two years in their current location and 94 percent were exposed to
      interventions in terms of getting free or subsidized condoms. Bivariate probit
      analysis revealed that comprehensive interventions are able to reach more
      vulnerable mobile FSWs effectively, e.g. new entrants, highly mobile, reported
      STIs, tested for HIV ever and serving a high volume of clients. The results
      complement the efforts of government and other agencies in response to HIV.
      However, the results highlight that specific issues related to various subgroups
      of this highly vulnerable population remain unaddressed calling for tailoring the
      response to the specific needs of the sub-groups. 

PMID- 25946931
TI  - Integrated method of teaching in Web Quest activity and its impact on
      undergraduate students' cognition and learning behaviors: a future trend in
      medical education.
AB  - INTRODUCTION: Web Quest is one of the new ways of teaching and learning that is
      based on research, and includes the principles of learning and cognitive
      activities, such as collaborative learning, social and cognitive learning, and
      active learning, and increases motivation. The aim of this study is to evaluate
      the Web Quest influence on students' learning behaviors. MATERIALS & METHODS: In
      this quasi-experimental study, which was performed on undergraduates taking a
      psychiatric course at Jahrom University of Medical Sciences, simple sampling was
      used to select the cases to be studied; the students entered the study through
      census and were trained according to Web Quest methodology. The procedure was to
      present the course as a case study and team work. Each topic included discussing
      concepts and then patient's treatment and the communicative principles for two
      weeks. Active participation of the students in response to the scenario and
      introduced problem was equal to preparing scientific videos about the disease and
      collecting the latest medical treatment for the disease from the Internet.Three
      questionnaires, including the self-directed learning Questionnaire, teamwork
      evaluation Questionnaire (value of team), and Buffard self-regulated
      Questionnaire, were the data gathering tools. RESULTS: The results showed that
      the average of self-regulated learning and self-directed learning (SDL) increased
      after the educational intervention. However, the increase was not significant. On
      the other hand, problem solving (P=0.001) and the value of teamwork (P=0.002),
      apart from increasing the average, had significant statistical values.
      CONCLUSIONS: In view of Web Quest's positive impacts on students' learning
      behaviors, problem solving and teamwork, the effective use of active learning and
      teaching practices and use of technology in medical education are recommended.

PMID- 25946933
TI  - The most common reasons and incentives of tendency to addiction in prisons and
      rehabilitation centres of Zahedan (Iran).
AB  - In most European countries the ratio of addicts and normal people is 1 to 5,000,
      and in some third world countries such as Morocco, Egypt, and South Africa this
      figure is 1 to 1,000. In Iran, the situation is worse, and there is one drug
      addict per 100 people. The research method in this study is analytical
      descriptive. The study population consisted of all rehabilitated addicted men and
      women who were spending their time in prison. Total sample size were 134 people
      (99 men and 35 women). A special designed questionnaire used to collect data,
      which included socio-demographic characteristics. The validity of the
      questionnaire has content validity and for reliability, Cronbach ? was used which
      was 0.78. The formal years of education was 4.3 year. The average age of the
      first drug use was 12 years for men and 22 years for women. Sixty-nine point
      seven percent of men used drugs with their friends and 31.4% of women used drug
      with their husbands. The men more than women, single men more than married women,
      and illiterates or poor literates were more at risk. Most men blamed bad friends
      and women blamed physical and psychological problems as the cause of addiction.
      The singles got addicted due to bad friends and married individuals were addicted
      due to emotional distress. The majority of age group (27-13 years), got addicted
      due to bad friends and older groups addicted due to emotional distress. In other
      words, the older the person gets, the influence of bad friends decreases, and the
      effect of psychological distress due to conflict and adversity increases. 

PMID- 25946934
TI  - Determining patients' satisfaction level with hospital emergency rooms in Iran: a
      meta-analysis.
AB  - Emergency department is one of the important parts of hospitals, and patients'
      satisfaction with this department significantly affects their overall
      satisfaction with the hospital. Therefore, evaluating patients' satisfaction
      level with the emergency part has been taken into account in different studies.
      The purpose of this study was to systematically review all available primary
      studies and their results and to evaluate patients' satisfaction level with
      emergency rooms of hospitals. In this study, previous documents were reviewed; to
      do this, national and international databases were searched electronically and
      related articles were extracted. Reference list of the published studies were
      also reviewed to increase sensitivity and to select a greater number of articles.
      Reviewing and studying titles and texts of the articles, repeated and unrelated
      cases were excluded. The remaining articles were entered into stat aver., 11 for
      meta-analysis. After meta-analysis, 24 articles were selected. The lowest and
      highest satisfaction level was 24 and 98.4% respectively. Meta-analysis results
      of studies showed that general evaluation of patients' satisfaction level with
      emergency rooms of hospitals was 68.9% in Iran. This meta-analysis revealed that
      patients' satisfaction level with performance and with the way services were
      presented in emergency rooms of hospitals was desirable in Iran. Concerning
      multifactorial nature of patients' satisfaction, it is necessary to take this
      matter into regular and routine consideration. 

PMID- 25946935
TI  - R&D implementation in a department of laboratory medicine and pathology: a
      systematic review based on pharmaceutical companies.
AB  - A systematic literature review on pharmaceutical companies may be a tool for
      guiding some procedures of R&D implementation in a department of Laboratory
      Medicine and Pathology. The use of pharmaceutical companies for this specific
      analysis arises from less variability of standards than healthcare facilities. In
      this qualitative and quantitative analysis, we focused on three useful areas of
      implementation, including R&D productivity, commercialization strategies, and
      expenditures determinants of pharmaceutical companies. Studies and reports of
      online databases from 1965 to 2014 were reviewed according to specific search
      terms. Initially, 218 articles and reports were found and examined, but only 91
      were considered appropriate and used for further analysis.  We identified some
      suggested implementation strategies relevant for marketing to enhance companies'
      own R&D strategies; such as reliability of companies on "sourcing-in" R&D
      facilities and "think-tank" events. Regardless of the study and of the country,
      cash flow and profitability always positively influenced R&D expenditure, while
      sales and firm size did not. We consider that handling R&D determinants should
      require caution. It seems critical that implementation of R&D systems is directly
      related with productivity, if it reflects dual embodiment of efficiency and
      effectiveness. Scrutinizing the determinants of R&D expenditures emphasizes
      significant factors that are worth to highlight when planning an R&D investment
      strategy. Although there is no receipt fitting every situation, we think that
      health care plan makers may find relevant data in this systematic review in
      creating an initial implementation framework. 

PMID- 25946937
TI  - A conceptual framework for evaluation of public health and primary care system
      performance in iran.
AB  - INTRODUCTION: The main objective of this study was to design a conceptual
      framework, according to the policies and priorities of the ministry of health to
      evaluate provincial public health and primary care performance and to assess
      their share in the overall health impacts of the community. METHODS: We used
      several tools and techniques, including system thinking, literature review to
      identify relevant attributes of health system performance framework and interview
      with the key stakeholders. The PubMed, Scopus, web of science, Google Scholar and
      two specialized databases of Persian language literature (IranMedex and SID) were
      searched using main terms and keywords. Following decision-making and collective
      agreement among the different stakeholders, 51 core indicators were chosen from
      among 602 obtained indicators in a four stage process, for monitoring and
      evaluation of Health Deputies. RESULTS: We proposed a conceptual framework by
      identifying the performance area for Health Deputies between other determinants
      of health, as well as introducing a chain of results, for performance, consisting
      of Input, Process, Output and Outcome indicators. We also proposed 5 dimensions
      for measuring the performance of Health Deputies, consisting of efficiency,
      effectiveness, equity, access and improvement of health status. CONCLUSION: The
      proposed Conceptual Framework illustrates clearly the Health Deputies success in
      achieving best results and consequences of health in the country. Having the
      relative commitment of the ministry of health and Health Deputies at the
      University of Medical Sciences is essential for full implementation of this
      framework and providing the annual performance report.

PMID- 25946936
TI  - Main determinants of catastrophic health expenditures: a Bayesian logit approach
      on Iranian household survey data (2010).
AB  - BACKGROUND: During recent decades, increase in both health care expenditures and
      improvement of the awareness as well as health expectations have created some
      problems with regard to finance healthcare expenditures so that the issue of
      health financing by households has been determined as a major challenge in health
      sector. According to the definition by the World Health Organization,
      catastrophic health expenditure is considered if financial contribution for
      health service is more than 40% of income remaining after subsistence needs have
      been met. OBJECTIVES: The purpose of our study was determination of Main factors
      on catastrophic health expenditures in Iranian households. PATIENTS & METHODS: In
      this study, using an econometrics Bayesian logit model, determinants of the
      appearance of catastrophic health expenditure based on household budget data
      collected in 2010 were evaluated. RESULTS: Among Iranian households, the
      following groups were more likely to encounter with unsustainable health
      expenditures: rural households, households with the numbers of the elderly more
      than 65 years, illiterate householders, unemployed householders, households with
      some unemployed persons, households in upper rank and households with larger
      equivalent household size were higher than the average of community could
      significantly predict catastrophic health expenditures. CONCLUSIONS: About 2.1%
      of households were faced with catastrophic health expenditures in 2010. Thus, the
      implemented policies could not make considerable and significant change in
      improving justice in financing in health systems.

PMID- 25946938
TI  - Effect of acupressure on fatigue in women with multiple sclerosis.
AB  - INTRODUCTION: Multiple sclerosis (MS) is the most common cause of progressive
      neurological disability. The prevalence of MS is much more common in women than
      men. The women are exposed to a variety of symptoms including fatigue.
      Acupressure is a noninvasive procedure that can be used to control symptoms
      including fatigue. The aim of the study was to evaluate the effect of acupressure
      on fatigue in women with multiple sclerosis. METHODS: A randomized clinical trial
      was conducted on 100 women with MS at Tehran MS Association. The subjects were
      equally allocated to experimental group and a placebo group (50 women per group)
      by blocking randomization method. The experimental group were received
      acupressure, at the true points (ST36, SP6, LI4) and the placebo group, were
      received touching at the same points. Fatigue was measured by a Fatigue Severity
      Scale (FSS) in the groups at immediately prior to, two and four weeks after the
      beginning of the intervention. The data was analyzed using descriptive and
      inferential statistics by SPSS version 17. RESULTS: The findings indicated no
      differences in demographic characteristics and the severity of fatigue at the
      baseline in two groups (p=0.54). But there were significant reductions of the
      mean score of fatigue in the experimental group compared to the placebo group
      immediately, two and four weeks after the intervention respectively (p=0.03,
      p?0/001, p=0.04). CONCLUSION: According to the findings, the study provided an
      alternative method for health care providers including nurses to train
      acupressure to the clients with MS to managing their fatigue.

PMID- 25946940
TI  - Comparison of laboratories directors' and assessors' opinions on challenges and
      solutions of standardization in Iran: a qualitative study.
AB  - OBJECTIVE: The quality medical laboratory services play a vital role in
      healthcare systems. Iran has set national standards based on the international
      standard ISO15189. These standards came into force in September 2007. Given the
      important role of both laboratories professional and assessors in the
      standardization, this study aims to compare and analyze medical laboratory
      directors' and assessors' opinions about this process, its challenges and
      relevant solutions. METHODS: This qualitative study was conducted on two
      populations in 2013. The first survey population consisted of 150 assessors. The
      second group consisted of directors working in medical laboratory settings. From
      all universities of medical sciences, 258 medical laboratories were randomly
      selected. Data were gathered using two open-ended questionnaires and analyzed
      using the thematic analysis. RESULTS: Challenges and relevant solutions regarding
      the standardization and standards, the assessment process and assessor,
      laboratories, external entities and contextual factors across laboratories
      directors and assessors were derived and compared. Both groups had a positive
      attitude towards the standardization process. However, they expressed some
      concerns regarding the process and accordingly proposed solutions to overcome the
      challenges. CONCLUSION: This study provides insights into the challenges and
      solutions of the standardization from two professional groups' viewpoint. These
      two factors are closely related and should be considered when implementing
      standards since a positive perception of them increases the likelihood of
      successful standardization. Similarities and divergences regarding challenges and
      solutions of the standardization, in turn, can provide insights into how this
      process can be improved and deserve policy makers' attention to continue the
      progress.

PMID- 25946941
TI  - Health, happiness and eating together: what can a large Thai cohort study tell
      us?
AB  - Our research investigates the significance of frequent solo consumption of main
      meals and the association with a holistic wellbeing measure of happiness using
      data from 39820 Thai Cohort Study members who completed 8-year follow-up in 2013.
      This nationwide cohort has been under study since 2005 to analyse the dynamics
      and determinants of the health-risk transition from infectious to chronic
      diseases. Here we analyse data from the 2009 and 2013 follow-ups. Approximately
      11% reported eating more than half of the main meals per week alone.
      Sociodemographic attributes associated with eating alone were being male, older
      age, unmarried, smaller household, lower income, and urban residence.
      Dissatisfaction with amount of spare time (ie 'busyness') was also linked to
      eating alone. In the multivariate cross-sectional model, reporting being unhappy
      was associated with frequent solo eating (Adjusted Odds Ratio - AOR 1.54, 95%
      Confidence Intervals 1.30-1.83). Stratified by age and sex groups, the effects
      were strongest among females (AOR 1.90 1.52-2.38).  A monotonic relationship
      linked frequent eating alone and 4-year longitudinal unhappiness. The larger the
      dose of unhappiness the greater the odds of eating alone - AOR 1.29, 1.31, 1.72
      after controlling for potential covariates. Having a meal is not only important
      for nutritional and health outcomes; it is also a vital part of daily social
      interaction. Our study provided empirical evidence from a non-Western setting
      that sharing meals could contribute to increasing happiness. 

PMID- 25946939
TI  - Chronic kidney disease screening methods and its implication for Malaysia: an in
      depth review.
AB  - Chronic Kidney Disease has become a public health problem, imposing heath, social
      and human cost on societies worldwide. Chronic Kidney Disease remains
      asymptomatic till late stage when intervention cannot stop the progression of the
      disease. Therefore, there is an urgent need to detect the disease early. Despite
      the high prevalence of Chronic Kidney Disease in Malaysia, screening is still
      lacking behind. This review discusses the strengths and limitations of current
      screening methods for Chronic Kidney Disease from a Malaysian point of view.
      Diabetic Kidney Disease was chosen as focal point as Diabetes is the leading
      cause of Chronic Kidney Disease in Malaysia. Screening for Chronic Kidney Disease
      in Malaysia includes a urine test for albuminuria and a blood test for serum
      creatinine. Recent literature indicates that albuminuria is not always present in
      Diabetic Kidney Disease patients and serum creatinine is only raised after
      substantial kidney damage has occurred.  Recently, cystatin C was proposed as a
      potential marker for kidney disease but this has not been studied thoroughly in
      Malaysia.  Glomerular Filtration Rate is the best method for measuring kidney
      function and is widely estimated using the Modification of Diet for Renal Disease
      equation. Another equation, the Chronic Kidney Disease Epidemiology Collaboration
      Creatinine equation was introduced in 2009. The new equation retained the
      precision and accuracy of the Modification of Diet for Renal Disease equation at
      GFR < 60ml/min/1.73m2, showed less bias and improved precision at
      GFR>60ml/min/1.73m2. In Asian countries, adding an ethnic coefficient to the
      equation enhanced its performance. In Malaysia, a multi-ethnic Asian population,
      the Chronic Kidney Disease Epidemiology Collaboration equation should be
      validated and the Glomerular Filtration Rate should be reported whenever serum
      creatinine is ordered. Reporting estimated Glomerular Filtration Rate will help
      diagnose patients who would have been otherwise missed if only albuminuria and
      serum creatinine are measured. 

PMID- 25946942
TI  - Personal, familial and environmental determinants of drug abuse: a causal
      comparative study.
AB  - AIMS: Two purposes were followed in this study: 1) comparing case and control
      group in eight factors separately and 2) performing a multivariate analysis for
      identifying risk and protective factors in relation to drug abuse. METHODS: A
      casual-comparative study was conducted to investigate the study goals. Fifty
      Cases in a convenient sampling of addicts referring to addiction withdrawal
      centers and fifty eligible controls (recruited in a randomly sampling) were
      identified. One-sample independent T-Test for a univariate and Logistic
      regression model for a multivariate was conducted. RESULTS: Univariate analysis:
      addicted group compared with control group, in terms of aggression, easy access
      to drugs and depression had higher scores and of other factors (self-esteem,
      religious affiliation, socioeconomic status, family environment and
      responsibility) cases had lower scores (p<0.05). Multivariate analysis: Easy
      access to drugs and depression identified as risk factors (OR>1) and high self
      esteem, family socioeconomic status and responsibility as protective (OR<1).
      CONCLUSIONS: Addiction is a multivariate phenomenon and before any intervention,
      we have to consider personal, familial and environmental factors and separate
      subjects by them. We can't give all of addicts the same prescription and follow a
      drug therapy approach to treat them. Any addict has a unique profile that should
      be taken into consideration.

PMID- 25946943
TI  - Modification of nursing education for upgrading nurses' participation: a thematic
      analysis.
AB  - BACKGROUND: The product of the educational nursing programs in Iran is training
      nurses who less have professional apprehension and commitment for participating
      in professional decisions. Whereas nurses especially those in high academic
      levels are expected to more involve in professional issues. OBJECTIVE: The aim of
      this study was to explore Iranian nurse leaders' experiences of making
      educational nursing policy with emphasizes on enhancement of nurses'
      participation in professional decisions. METHODS: We used a qualitative design
      with thematic analysis approach for data gathering and data analysis. Using
      purposive sampling we selected 17 experienced nurses in education and making
      educational nursing policies. Data gathered by open deep semi-structured face to
      face interviews. We followed six steps of Braun and Clarke for data analysis.
      RESULTS: In order to enhance nurses' participation in professional decisions they
      need to be well educated and trained to participate in community and meet
      community needs. The three main themes that evolved from analysis included
      opportunities available for training undergraduate students, challenges for PhD
      nurses and general deficiencies in nursing education. The second theme includes
      three sub-themes; namely, the PhD curriculum, PhD nurses' attitudes and PhD
      nurses' performance. CONCLUSIONS: We need for revising and directing nursing
      education toward service learning, community based need programs such as diabetes
      and driving accidents and also totally application of present educational
      opportunities. The specialization of nursing and the establishment of specialized
      nursing associations, the emphasis on teaching the science of care and
      reinforcing the sense of appreciation of pioneers of nursing in Iran are among
      the directions offered in the present study.

PMID- 25946944
TI  - Depressive symptoms effect on self care behavior during the first month after
      myocardial infarction.
AB  - AIM: To determine the effect of severity of depression symptoms on self care
      behavior in 15th and 30th day after myocardial infarction (MI). MATERIALS &
      METHODS: Gathering data for this cross sectional study was done by Beck
      depression and self care behavior questionnaires in a heart especial hospital in
      Rasht in north of Iran .Sample size was 132 after MI patients and data collected
      from June 2011 to January 2012. RESULTS: Scores of depression symptoms in 15th
      and 30th day after MI and score of self care behavior in these days had
      significant difference (P<0.0001) .Spearman test showed self care behavior had
      significant relationship with depression symptoms (P<0.0001). GEE model also
      showed with control of socio demographic and illness related factors, depression
      symptoms can decrease self care behavior scores (P<0.001). CONCLUSION: Severity
      of depression symptoms increase in 15th to 30th day after MI .This issue can
      affect on self care behavior. This issue is emphasized on nurses' notice to plan
      suitable self care program for these patients.

PMID- 25946945
TI  - Prediction of breast cancer survival through knowledge discovery in databases.
AB  - The collection of large volumes of medical data has offered an opportunity to
      develop prediction models for survival by the medical research community. Medical
      researchers who seek to discover and extract hidden patterns and relationships
      among large number of variables use knowledge discovery in databases (KDD) to
      predict the outcome of a disease. The study was conducted to develop predictive
      models and discover relationships between certain predictor variables and
      survival in the context of breast cancer. This study is Cross sectional. After
      data preparation, data of 22,763 female patients, mean age 59.4 years, stored in
      the Surveillance Epidemiology and End Results (SEER) breast cancer dataset were
      analyzed anonymously. IBM SPSS Statistics 16, Access 2003 and Excel 2003 were
      used in the data preparation and IBM SPSS Modeler 14.2 was used in the model
      design. Support Vector Machine (SVM) model outperformed other models in the
      prediction of breast cancer survival. Analysis showed SVM model detected ten
      important predictor variables contributing mostly to prediction of breast cancer
      survival. Among important variables, behavior of tumor as the most important
      variable and stage of malignancy as the least important variable were identified.
      In current study, applying of the knowledge discovery method in the breast cancer
      dataset predicted the survival condition of breast cancer patients with high
      confidence and identified the most important variables participating in breast
      cancer survival. 

PMID- 25946946
TI  - Sexual and reproductive health problems of female university students in Iran: a
      qualitative study.
AB  - OBJECTIVE: Youth is defined as the time of transition into adulthood and an
      important period in a person's life. During this period new behavior is learned
      easier than adulthood. Therefore, special attention has to be necessarily paid to
      this period in order to promote the health. Addressing adolescent reproductive
      health issues is also a critical factor METHODS: This research was a qualitative
      study conducted from January 2014 to July 2014. Data from focus group discussions
      and semi-structured interviews with 25 female students and 10 key members of the
      university (including university authorities, consultants, reproductive health
      professionals and university officials) was collected and all interviews were
      recorded, formulated and classified. RESULTS: The mean age of participants was
      22.43 years. A total of 8 students majored in geology, 5 majored in chemistry, 3
      in statistics, 3 in mathematics, and 6 in biology. 17 had a bachelor's degree, 3
      master's degree and 5 doctorate degree. Majority of students (82.4%) were never
      married and 23 of them lived in dormitories. The following three main themes were
      extracted from the interviews: Reproduction thought as pregnancy; the taboo of
      sex; and inappropriate relation between parents and children. CONCLUSION: Most
      participants stressed the need to provide reproductive health services for young
      girls.

PMID- 25946947
TI  - Clinical manifestation and risk factors of tuberculosis infection in Malaysia:
      case study of a community clinic.
AB  - INTRODUCTION: The main aim of this study was to describe the clinical
      manifestation of tuberculosis infection cases in Malaysia and to determine the
      individual risk factors for their occurrence. METHODOLOGY: The study adopted a
      quantitative research approach with use of descriptive statistical approach. The
      study setting was a community clinic which treats walk in patients who are mainly
      living and working in the surrounding areas. The study was conducted for a period
      of one year. All tuberculosis patients who sought treatment in the clinic during
      the time were included in this study. The total number of cases was 40. Data was
      collected from the medical records of the tuberculosis patients. The risk factors
      selected for investigation were demographic characteristics of age and sex,
      personal habits such as smoking, drug use and alcohol and presence of diseases
      such as human immunodeficiency virus positive (HIV+), diabetes mellitus, cancer,
      cyanotic heart disease, renal failure and steroid use. RESULTS: Patients in the
      age group ranging from 41 to 50 years had the highest incidence of the infection.
      Smoking appears to be the most important risk factor for contracting followed by
      drug abuse, HIV+ infection and diabetes mellitus. CONCLUSIONS: People with
      diseases such as diabetes mellitus and HIV that are high risk factors for TB
      should be screened for TB so that early detection and intervention is possible.
      Educational programs should be carried out to create awareness among the at risk
      groups.

PMID- 25946948
TI  - Lidocaine-Prilocaine Cream as Analgesia for IUD Insertion: A Prospective,
      Randomized, Controlled, Triple Blinded Study.
AB  - INTRODUCTION: Copper IUD is a long term and reversible contraception which equals
      tubal ligation in terms of sterilization. One of the barriers to using this
      contraception method is the fear and the pain associated with its insertion.
      Eutectic mixture of local anesthetics (EMLA) 5% is a local anesthetic that
      contains 25 mg lidocaine and 25 mg of prilocaine per gram. Application of topical
      analgesic cream to the cervix for laser surgery, hysteroscopy and
      hysterosalpingography is known Aims: this study aimed to determine the effect of
      EMLA on IUD insertion pain. METHODS: This triple blind clinical trial was
      conducted on 92 women in a clinic in Hamedan in 2012. After applying the cream on
      the cervix, pain in three steps, after using Tenaculum, after inserting
      hystrometr and after inserting IUD and removing IUD insertion tube were assessed
      with visual analog scale and were compared in EMLA group and placebo group
      Statistical analysis used to determine and compare the pain of independent t
      tests, Mann-Whitney U test and repeated measures analysis of variance and chi
      square tests to determine the homogeneity of variables and Fisher's exact test
      was used. RESULTS: Insertion hystrometr was determined as the most painful IUD
      insertion. The mean pain at step 2 (inserting hystrometr) was (3.11+/-2.53) in
      EMLA group, (5.23+/-2.31) in placebo group. EMLA cream significantly reduced the
      pain after using tenaculum (P<0.001), pain inserting Hystrometr (P< 0.001) and
      pain at IUD insertion and removing insertion tube (P< 0.001) CONCLUSIONS: Topical
      Application of EMLA 5% cream as a topical anesthetic on the cervix before
      insertion IUD reduced the pain during this procedure.

PMID- 25946949
TI  - Home Health Care (HHC) Managers Perceptions About Challenges and Obstacles that
      Hinder HHC Services in Jordan.
AB  - Home care aims at supporting people with various degrees of dependency to remain
      at home rather than use residential, long-term, or institutional-based nursing
      care. Demographic, epidemiological, social, and cultural trends in Jordan as in
      other countries are changing the traditional patterns of care with growing
      emphasis on home care. The purpose of this study is to highlight the most common
      challenges related to home health care (HHC) services in Jordan as perceived by
      the managers of HHC agencies. METHODS: A descriptive qualitative design that
      depends on focus group discussions has been used to collect data from a sample of
      18 managers who met the selection criteria and who are willing to participate,
      the study found that, the main challenges of HHC services as perceived by
      managers were: shortage of female staff, lack of governance and regulation, poor
      management, unethical practices, lack of referral systems, and low accessibility
      of the poor and less privileged as HHC services are not included in health
      insurance schemes, it concludes also that the home health care industry in Jordan
      is facing many challenges and problems that may have negative effects on the
      effectiveness, efficiency, equity and quality of services and should be addressed
      by health policy makers.

PMID- 25946950
TI  - Dynamics of psychological crisis experience with psychological consulting by
      gestalt therapy methods.
AB  - Dynamics of experience as such and its corporeal, emotional and cognitive
      elements in the situation of psychological consulting provisioning is covered.
      The aim of research was to study psychological crisis experience dynamics in the
      situation when psychological consulting by gestalt therapy methods is provided.
      Theoretical analysis of the problem of crisis situations, phenomenon and
      structural, and dynamic organization of experience of the subject of consulting
      have been carried out. To fulfill research project test subjects experience
      crisis situation have been selected, studied in the situation when they provided
      psychological consulting by methods of gestalt therapy, and methodology of study
      of crisis situations experience has been prepared. Specifics of psychological
      crisis experience have been revealed and its elements in different stages of
      psychological consulting by gestalt therapy methods. Dynamics of experience of
      psychological crisis and its structural elements have been revealed and reliable
      changes in it have been revealed. Dynamics of psychological crisis experience and
      its structural elements have been revealed and reliable changes in it have been
      revealed. "Desiccation" of experience is being observed, releasing its
      substantiality of negative impression to the end of consulting and development of
      the new experience of control over crisis situation. Interrelations of structural
      elements of experience in the process of psychological consulting have been
      shown. Effecting one structure causes reliable changes in all others structural
      elements of experience. Giving actual psychological help to clients in crisis
      situation by methods of gestalt therapy is possible as it was shown in
      psychological consulting sessions. Structure of client's request has been
      revealed - problems of personal sense are fixed as the most frequent cause of
      clients' applications, as well as absence of choices, obtrusiveness of negative
      thoughts, tend to getting stuck on events took place in the past, drawing into
      oneself, etc. 

PMID- 25946951
TI  - Assessment of carcinogenic and non-carcinogenic risk lead in bottled water in
      different age groups in Bandar Abbas Ciry, Iran.
AB  - The presence of heavy metals such as lead in drinking water resources can be
      dangerous for human because of toxicity and biological accumulation. The
      consumption of water or food which contains lead in high concentration can lead
      to prevent from Hemoglobin Synthesis (Anemia) and Kidney diseases. In this
      present study, the researcher collected 432 samples of bottled water in the
      popular marks in summer and winter from the surface of Bandar Abbas. The lead
      concentration was measured by atomic absorption Spectrophotometer in model DR2800
      through the Dithizone method. CDI, R and HQ which are caused by lead for adult
      men, women and children, have been calculated and evaluated through the equations
      of EPA and WHO. The mean concentration of lead, which is 3.46+/- 0.47 ug/l, and
      its range, which is 1.9-17.6 ug/l, are lower than the guideline of WHO (10 ug/l)
      and MPC of EPA is (15 ug/l). But the 40 samples of the bottled water (9.2%) have
      the concentration higher than guideline WHO and 8 samples (1.85%) has the
      concentration higher than the permissible limits of the EPA. CDI in different age
      groups is as following manner: Children>adult men>adult women. CDI in children is
      more than twice as much as in the adult men and women. The R of lead for children
      (24E-7), adult men (11E-7) and for adult women (10E-7) are more than the
      acceptable level of R in EPA (1E-6) but less than the acceptable level of R in
      WHO (1E-4). Since HQ of adult men (34E-5), adult women (31E-5) and children (84E
      5), is lower than 1, it can be said that the population of Bandar Abbas is in a
      safe area regarding the HQ of the bottled water's lead. 

PMID- 25946952
TI  - Message from the Technical Editor-in-Chief.

PMID- 25946954
TI  - Waste electrical and electronic equipment management in Botswana: Prospects and
      challenges.
AB  - The management of waste electronic and electrical equipment (WEEE) is a major
      challenge in developing and transition countries. The paper investigates recent
      strategies to manage this waste stream in an environmentally sound way. Obsolete
      electrical and electronic equipment (EEE) are a complex waste category containing
      both hazardous and valuable substances. Many countries and regions in the world
      are undertaking extensive scientific research to plan and develop effective
      collection and treatment systems for end-of-life EEE. In developing countries
      such as Botswana, effective strategies that cover all stages throughout the
      lifecycle of products, particularly at the end-of-life, still lag behind.
      Infrastructure, pre-processing, and end-processing facilities and innovative
      technologies for end-of-life management of e-waste are noticeably absent due to
      lack of investment and high costs of its management. The objective of the paper
      is to present the e-waste situation in Botswana, highlighting (a) measures taken
      in the form of legislative and policy regulations; (b) existing practices to
      manage e-waste; and (c) effective solutions for e-waste management in emerging
      economies. Studies from other countries on e-waste management issues provided
      insights on the "best" technical and logistical pre-processing and end-processing
      strategies to treat hazardous waste. The paper also highlights key societal
      factors that affect successful implementation of cost-effective collection and
      value recovery of end-of-life EEE. These include unavailability of national "e
      waste policy," absence of formal take-back system, absence of financing and
      subsidies, inadequate source separation programmes, absence of technical and
      logistical integration of pre-processing and end-processing facilities, and
      limited infrastructure and access to technologies and investment. Effective
      strategies such as an "integrated approach" (mixed options), access to
      technologies, establishment of pre-processing and end-processing facilities and
      optimization of logistics, optimizing diversion of e-waste from disposal sites,
      and investment in e-waste are suggested to manage this complex waste stream in an
      environmentally sound way.

PMID- 25946955
TI  - Emission factors for fugitive dust from bulldozers working on a coal pile.
AB  - A study of a Powder River Basin (PRB) coal pile found that fugitive emissions
      from natural and human activity each produced similar levels of downwind fine +
      coarse (i.e., smaller than 10 um, or PM10) particle mass concentrations. Natural
      impacts were statistically removed from downwind measurements to estimate
      emission factor Ev for bulldozers working on the pile. The Ev determined here was
      similar in magnitude to emission factors (EFs) computed using a U.S.
      Environmental Protection Agency (EPA) formulation for unpaved surfaces at
      industrial sites, even though the latter was not based on data for coal piles. EF
      formulations from this study and those in the EPA guidance yield values of
      similar magnitude but differ in the variables used to compute Ev variations. EPA
      studies included effects of surface silt fraction and vehicle weight, while the
      present study captured the influence of coal moisture. Our data indicate that the
      relationship between PRB coal fugitive dust Ev (expressed as mass of PM10 emitted
      per minute of bulldozer operation) and coal moisture content Mc (in percent) at
      the study site is best expressed as Ev =10(f(Mc())) where f(Mc) is a function of
      moisture. This function was determined by statistical regression between
      log10(Ev) and Mc where both Ev and Mc are expressed as daily averages of
      observations based on 289 hours sampled during 44 days from late June through mid
      November of 2012. A methodology is described that estimates Mc based on available
      meteorological data (precipitation amount and solar radiation flux). An example
      is given of computed variations in daily Ev for an entire year. This illustrates
      the sensitivity of the daily average particulate EF to meteorological variability
      at one location. Finally, a method is suggested for combining the moisture
      sensitive formulation for Ev with the EPA formulation to accommodate a larger
      number of independent variables that influence fugitive emissions.

PMID- 25946956
TI  - Emission of submicron aerosol particles in cement kilns: Total concentration and
      size distribution.
AB  - Cement plants are responsible for particle and gaseous emissions into the
      atmosphere. With respect to particle emission, the greater part of is in the
      range from 0.05 to 5.0 um in diameter. In the last years attention was paid to
      submicron particles, but there is a lack of available data on the emission from
      stationary sources. In this paper, concentration and size distribution of
      particles emitted from four cement kilns, in relationship to operational
      conditions (especially the use of alternative fuel to coal) of the clinker
      process are reported. Experimental campaigns were carried out by measuring
      particles concentration and size distribution at the stack of four cement plants
      through condensation particle counter (CPC) and scanning mobility particle sizer
      spectrometer (SMPS). Average total particle number concentrations were between
      2000 and 4000 particles/cm3, about 8-10 times lower that those found in the
      corresponding surrounding areas. As for size distribution, for all the
      investigated plants it is stable with a unimodal distribution (120-150 nm),
      independent from the fuel used.

PMID- 25946957
TI  - Graphene-supported CoPc/TiO2synthesized by sol-gel-hydrothermal method with
      enhanced photocatalytic activity for degradation of the typical gas of landfill
      exhaust.
AB  - This work was focused on the enhanced photocatalytic activity of cobalt
      phthalocyanine (CoPc)/TiO2under visible light irradiation supported on reduced
      graphene oxide (RGO). A series of RGO/CoPc/TiO2nanocomposites were synthesized
      via sol-gel-hydrothermal method. The photocatalysts were characterized by X-ray
      diffraction, BET surface area, Scanning electron microscopy, Raman spectra,
      Fourier transform infrared spectra, UV-Vis spectra and Photoluminescence spectra.
      The results demonstrated that the TiO2existed as anatase phase both of
      CoPc/TiO2and RGO/CoPc/TiO2composites, and the absorption range in visible light
      of RGO/CoPc/TiO2composites were broadened further. The photodegradation results
      of diethyl sulfide, the typical gas of landfill exhaust, under visible light
      revealed that RGO/CoPc/TiO2nanocomposites exhibited much higher photocatalytic
      activity than CoPc/TiO2and pure TiO2, indicating the ideal amount of RGO was 7.5
      wt.%, the optimal amount of 7.5% RGO/CoPc/TiO2composite on each plat was 0.3g and
      the degradation efficiency of diethyl sulfide was about 90%.

PMID- 25946958
TI  - Study on the air pollution in typical transportation microenvironment:
      Characteristics and health risks.
AB  - The concentration of formaldehyde in micro-traffic atmospheric environment
      (including buses, cars, bus stations, and traffic artery) of Lin'an City was
      carefully investigated. The results showed that the formaldehyde average
      concentration was 0.0162 mg/m3 in the buses, 0.0225 mg/m3 in the cars, 0.0047
      mg/m3 in the West Bus Stations, and 0.0133 mg/m3 in the East Bus Stations. The
      concentration of formaldehyde along the traffic artery decreased with the height
      increased. From 0 to 140 cm, the formaldehyde concentration decreased from 0.031
      to 0.018 mg/m3. The formaldehyde concentration decreased when far away from the
      traffic artery. When the distance reached 200 m, the formaldehyde concentration
      decreased from 0.018 to 0.005 mg/m3. Based on the health risk assessment model,
      using 1 hr as the average retention time, the average health risk in buses, cars,
      and West/East Bus Stations was 2.106 * 10-4, 2.925 * 10-4, and 1.157 * 10-4,
      respectively.

PMID- 25946959
TI  - Using growth and decline factors to project VOC emissions from oil and gas
      production.
AB  - Projecting future-year emission inventories in the oil and gas sector is
      complicated by the fact that there is a life cycle to the amount of production
      from individual wells and thus from well fields in aggregate. Here we present a
      method to account for that fact in support of regulatory policy development. This
      approach also has application to air quality modeling inventories by adding a
      second tier of refinement to the projection methodology. Currently, modeling
      studies account for the future decrease in emissions due to new regulations based
      on the year those regulations are scheduled to take effect. The addition of a
      year-by-year accounting of production decline provides a more accurate picture of
      emissions from older, uncontrolled sources. This proof of concept approach is
      focused solely on oil production; however, it could be used for the activity and
      components of natural gas production to compile a complete inventory for a given
      area.

PMID- 25946960
TI  - A self-consistent method to assess air quality co-benefits from U.S. climate
      policies.
AB  - Air quality co-benefits can potentially reduce the costs of greenhouse gas
      mitigation. However, whereas many studies of the cost of greenhouse gas
      mitigation model the macroeconomic welfare impacts of mitigation, most studies of
      air quality co-benefits do not. We employ a U.S. computable general equilibrium
      economic model previously linked to an air quality modeling system and enhance it
      to represent the economy-wide welfare impacts of fine particulate matter. We
      present a first application of this method to explore the efficiency and
      distributional implications of a Clean Energy Standard (CES) and a Cap and Trade
      (CAT) program that both reduce CO2emissions by 10% in 2030 relative to 2006. We
      find that co-benefits from fine particulate matter reduction (median $6; $2 to
      $10/tCO2) completely offset policy costs by 110% (40% to 190%), transforming the
      net welfare impact of the CAT into a gain of $1 (-$5 to $7) billion 2005$. For
      the CES, the corresponding co-benefit (median $8; $3 to $14/tCO2) is a smaller
      fraction (median 5%; 2% to 9%) of its higher policy cost. The eastern United
      States garners 78% and 71% of co-benefits for the CES and CAT, respectively. By
      representing the effects of pollution-related morbidities and mortalities as an
      impact to labor and the demand for health services, we find that the welfare
      impact per unit of reduced pollution varies by region. These interregional
      differences can enhance the preference of some regions, such as Texas, for a CAT
      over a CES, or switch the calculation of which policy yields higher co-benefits,
      compared with an approach that uses one valuation for all regions. This framework
      could be applied to quantify consistent air quality impacts of other pricing
      instruments, subnational trading programs, or green tax swaps.

PMID- 25946961
TI  - Absorption of gaseous toluene in aqueous solutions of some kinds of fluorocarbon
      surfactant.
AB  - A self-designed device was applied to treat a simulated exhaust gas loaded with
      toluene by aqueous solutions of five kinds of fluorocarbon surfactant (FS-3100,
      FS-22, FSN-100, FSO-100 and FSG) under the controlled laboratory conditions. The
      simulated exhaust gas is generated by a mixture of clean air and toluene vapor,
      and its toluene concentration can be controlled by changing the volume ratio of
      the inlet air to the vapor. Two mass transfer methods: liquid-liquid transfer and
      gas-liquid transfer, were compared for their toluene saturation capacities of
      these absorbent solutions, and it was found that more toluene was dissolved by
      the liquid-liquid transfer than by the gas-liquid transfer. According to the
      saturation capacities of these absorbent solutions and their Henry's Constants,
      FSO-100 is the best absorbent to treat the simulated exhaust gas and was selected
      for further experiments. The FSO-100 absorbent solution with a concentration of
      0.1 % shows an efficient absorption to the simulated exhaust gas, with a toluene
      saturation capacity of 4.2 mg/g. Heating distillation (90- 95 oC) is highly
      efficient to recover toluene from the FSO-100 absorbent solution as well as
      regenerate it. A toluene recovery of about 85 % was achieved. The regenerated
      absorption solution can keep its initial toluene absorption capacity during the
      reuse.

PMID- 25946962
TI  - Preliminary study on removing Cs+/Sr2+ by activated porous calcium silicate-A by
      product from high-alumina fly ash recycling industry.
AB  - 137Cs+/90Sr2+-containing radioactive wastewater is one of the most important
      problems that the world has been facing with. A by-product, activated porous
      calcium silicate, is generated at high levels by the pre-desiliconizing and soda
      lime-sintering processes for producing Al2O3from high-alumina fly ash. In order
      to examine if this by-product could be used as an absorbent for removal of
      137Cs+/90Sr2+ from radioactive wastewater, various parameters, such as pH,
      adsorbent dose, contact time, and initial concentration, were discussed. Results
      indicated that the equilibrium reached in about 2 hr. Activated porous calcium
      silicate was highly pH sensitive and able to remove Cs(+)/Sr2+ in a near-neutral
      environment. The adsorption equilibrium was best described by Freundlich isotherm
      equations, and the adsorption of Cs+/Sr2+ was a physical process. The adsorption
      kinetic data could be better fitted by the pseudo-second-order model, and the
      adsorption was controlled by multidiffusion. Current study showed that activated
      porous calcium silicate has a good adsorption of Cs+/Sr2+ for their removal.
      However, other characteristics, such as selectivity because of coexisting
      cations, elution and regeneration, thermal stability, and acid resistance, should
      be discussed carefully before using it in an actual field.

PMID- 25946963
TI  - Removal of lead from cathode ray tube funnel glass by generating the sodium
      silicate.
AB  - In the disposal of electronic waste, cathode ray tube (CRT) funnel glass is an
      environmental problem of old television sets. Removal of the lead from CRT funnel
      glass can prevent its release into the environment and allow its reuse. In this
      research, we reference the dry progress productive technology of sodium silicate,
      the waste CRT glass was dealt with sodium silicate frit melted and sodium
      silicate frit dissolved. Adding a certain amount of Na 2CO3to the waste CRT glass
      bases on the material composition and content of it, then the specific modulus of
      sodium silicate frit is obtained by melting progress. The silicon, potassium and
      sodium compounds of the sodium silicate frit are dissolved under the conditions
      of high temperature and pressure by using water as solvent, which shows the
      tendency that different temperature, pressure, liquid-solid ratio and dissolving
      time have effect on the result of dissolving. At 175 degrees C(0.75MPa), liquid
      solid ratio is 1.5:1, the dissolving time is 1h, the dissolution rate of sodium
      silicate frit is 44.725%. By using sodium sulfide to separate hydrolysis solution
      and to collect lead compounds in the solution, the recovery rate of lead in
      dissolving reached 100% and we can get clean sodium silicate and high purity of
      lead compounds. The method presented in this research can recycle not only the
      lead but also the sodium, potassium and other inorganic minerals in CRT glass and
      can obtain the comprehensive utilization of leaded glass.

PMID- 25946964
TI  - Quantitative headspace analysis of selected odorants from latrines in Africa and
      India.
AB  - This analytical investigation focuses on the quantification of odorant molecules
      in the headspace of latrines. Hydrogen sulfide and methyl mercaptan were
      derivatized under a more stable N-ethyl maleimide conjugate. Since the amount of
      odorant molecules is very low in the gas phase, we developed a method that had
      two steps of concentration. The first step consisted of the accumulation of
      volatiles in buffered water by bubbling 350 L of air in a bottle. The second step
      consisted of loading the water on a 1 g solid-phase extraction cartridge,
      shipping it to our laboratories, and desorbing with Et2O, which achieved a total
      concentration factor of 3.5 * 10(6). The acidification of the water phase gave us
      access to the acids, and an additional bottle containing an acidic ion-exchange
      resin gave us access to trimethyl amine. The limits of quantification in the gas
      phase were 8.7 * 10(-4) MUg/L air for hydrogen sulfide, 1 * 10(-4) MUg/L air for
      methyl mercaptan, 1 * 10(-3) MUg/L air for butyric acid, 1 * 10(-4) MUg/L air for
      p-cresol, 1 * 10(-5) MUg/L air for indole, and 1 * 10(-5) MUg/L air for skatole.
      The system was calibrated by using olfactometers, which can deliver a precisely
      known quantity of volatiles into the air. We were able to quantify all compounds
      near their odor detection thresholds (ODTs). All ODTs were measured in our
      laboratory with the same olfactometry method. This allowed accurate and
      comparable ODT values for malodorant compounds from toilets. 

PMID- 25946965
TI  - To what extent can charge localization influence electron injection efficiency at
      graphene-porphyrin interfaces?
AB  - Controlling the electron transfer process at donor-acceptor interfaces is a
      research direction that has not yet seen much progress. Here, with careful
      control of the charge localization on the porphyrin macrocycle using beta
      cyclodextrin as an external cage, we are able to improve the electron injection
      efficiency from cationic porphyrin to graphene carboxylate by 120%. The detailed
      reaction mechanism is also discussed. 

PMID- 25946966
TI  - Surgical anatomy of the superior orbit on ultra-high-resolution MRI at 9.4 Tesla.
AB  - BACKGROUND: A good understanding of the anatomical details is required to ensure
      optimal results during surgery of the orbit. Several indications for orbital
      surgery require biopsy, resection, or reconstructive procedures. The intricate
      relationships between the orbital septum and adjacent structures of the upper
      orbit can cause difficulties in interpreting the surgical anatomy of this region.
      The purpose of this study was to acquire further insight into the anatomy of the
      superior part of the orbit, with special attention paid to the orbital septum.
      METHODS: An ex-vivo study was performed using magnetic resonance imaging (MRI) at
      9.4 Tesla (isotropic resolution = 20 MUm) on six human cadaver specimens to
      examine the superior-medial half of the orbit. To visualise the posterior layers
      of the upper orbit, a dissection of three of the orbits was performed prior to
      the MRI examination, and a flexible PVC sheet was introduced above the levator
      muscle. RESULTS: The technique enabled a visualisation of anatomically important
      landmarks of the anterior and posterior parts of the upper orbit at a resolution
      near histological levels; to the authors' knowledge, this visualisation has not
      been reported previously. A posterior continuation of the orbital septum, which
      forms a distinct anatomical structure, is revealed. CONCLUSIONS: The posterior
      aspect of the orbital septum separates the levator muscle and the orbital fat
      pad. Between these two structures, a surgical corridor is formed using MRI,
      enabling alternative access to the superior part of the orbit; this alternative
      access might be less invasive because the orbital septum remains undamaged.

PMID- 25946967
TI  - IkappaBbeta enhances the generation of the low-affinity NFkappaB/RelA homodimer.
AB  - The NFkappaB family of dimeric transcription factors regulate inflammatory and
      immune responses. While the dynamic control of NFkappaB dimer activity via the
      IkappaB-NFkappaB signalling module is well understood, there is little
      information on how specific dimer repertoires are generated from Rel family
      polypeptides. Here we report the iterative construction-guided by in vitro and in
      vivo experimentation-of a mathematical model of the Rel-NFkappaB generation
      module. Our study reveals that IkappaBbeta has essential functions within the Rel
      NFkappaB generation module, specifically for the RelA:RelA homodimer, which
      controls a subset of NFkappaB target genes. Our findings revise the current dogma
      of the three classical, functionally related IkappaB proteins by distinguishing
      between a positive 'licensing' factor (IkappaBbeta) that contributes to
      determining the available NFkappaB dimer repertoire in a cell's steady state, and
      negative feedback regulators (IkappaBalpha and -E) that determine the duration
      and dynamics of the cellular response to an inflammatory stimulus. 

PMID- 25946968
TI  - Individual and School Organizational Factors that Influence Implementation of the
      PAX Good Behavior Game Intervention.
AB  - Evidence-based interventions are being disseminated broadly in schools across the
      USA, but the implementation levels achieved in community settings vary
      considerably. The current study examined the extent to which teacher and school
      factors were associated with implementation dosage and quality of the PAX Good
      Behavior Game (PAX GBG), a universal classroom-based preventive intervention
      designed to improve student social-emotional competence and behavior.
      Specifically, dosage (i.e., number of games and duration of games) across the
      school year and quality (i.e., how well the game is delivered) of PAX GBG
      implementation across four time points in a school year were examined.
      Hierarchical linear modeling was used to examine the association between teacher
      level factors (e.g., demographics, self-reports of personal resources, attitudes
      toward the intervention, and workplace perceptions) and longitudinal
      implementation data. We also accounted for school-level factors, including
      demographic characteristics of the students and ratings of the schools'
      organizational health. Findings indicated that only a few teacher-level factors
      were significantly related to variation in implementation. Teacher perceptions
      (e.g., fit with teaching style, emotional exhaustion) were generally related to
      dosage, whereas demographic factors (e.g., teachers' age) were related to
      quality. These findings highlight the importance of school contextual and
      proximal teacher factors on the implementation of classroom-based programs. 

PMID- 25946969
TI  - Clustering Methods with Qualitative Data: a Mixed-Methods Approach for Prevention
      Research with Small Samples.
AB  - Qualitative methods potentially add depth to prevention research but can produce
      large amounts of complex data even with small samples. Studies conducted with
      culturally distinct samples often produce voluminous qualitative data but may
      lack sufficient sample sizes for sophisticated quantitative analysis. Currently
      lacking in mixed-methods research are methods allowing for more fully integrating
      qualitative and quantitative analysis techniques. Cluster analysis can be applied
      to coded qualitative data to clarify the findings of prevention studies by aiding
      efforts to reveal such things as the motives of participants for their actions
      and the reasons behind counterintuitive findings. By clustering groups of
      participants with similar profiles of codes in a quantitative analysis, cluster
      analysis can serve as a key component in mixed-methods research. This article
      reports two studies. In the first study, we conduct simulations to test the
      accuracy of cluster assignment using three different clustering methods with
      binary data as produced when coding qualitative interviews. Results indicated
      that hierarchical clustering, K-means clustering, and latent class analysis
      produced similar levels of accuracy with binary data and that the accuracy of
      these methods did not decrease with samples as small as 50. Whereas the first
      study explores the feasibility of using common clustering methods with binary
      data, the second study provides a "real-world" example using data from a
      qualitative study of community leadership connected with a drug abuse prevention
      project. We discuss the implications of this approach for conducting prevention
      research, especially with small samples and culturally distinct communities. 

PMID- 25946970
TI  - Is the cervical fascia an anatomical proteus?
AB  - The cervical fasciae have always represented a matter of debate. Indeed, in the
      literature, it is quite impossible to find two authors reporting the same
      description of the neck fascia. In the present review, a historical background
      was outlined, confirming that the Malgaigne's definition of the cervical fascia
      as an anatomical Proteus is widely justified. In an attempt to provide an
      essential and a more comprehensive classification, a fixed pattern of description
      of cervical fasciae is proposed. Based on the morphogenetic criteria, two fascial
      groups have been recognized: (1) fasciae which derive from primitive fibro
      muscular laminae (muscular fasciae or myofasciae); (2) fasciae which derive from
      connective thickening (visceral fasciae). Topographic and comparative approaches
      allowed to distinguish three different types of fasciae in the neck: the
      superficial, the deep and the visceral fasciae. The first is most connected to
      the skin, the second to the muscles and the third to the viscera. The muscular
      fascia could be further divided into three layers according to the relationship
      with the different muscles. 

PMID- 25946971
TI  - LATS2 inhibits the activity of NF-kappa B signaling by disrupting the interaction
      between TAK1 and IKKbeta.
AB  - NF-kappaB signaling plays very important role in the tumorigenesis of nonsmall
      cell lung cancer (NSCLC). However, the molecular mechanisms for the dysregulation
      of NF-kappaB signaling in NSCLC have not been fully understood. In the previous
      reports, we have showed that large tumor suppressor gene 2 (LATS2) inhibited NF
      kappaB signaling in NSCLC cells, whereas the details for the mechanism remain
      unknown. Here, we reported that LATS2 is a suppressor of tumor necrosis factor
      (TNF-alpha)-induced NF-kappaB signaling by inhibiting the interaction between
      TAK1 and IKKbeta. Overexpression of LATS2 largely blocked TNF-alpha-induced NF
      kappaB activation and IkappaBalpha degradation, whereas knockdown of LATS2 showed
      the opposing results. Mechanistically, we identified that LATS2 interacted with
      IKKbeta and blocked the interaction between IKKbeta and TAK1. Our results
      indicate that LATS2 functions as a pivotal negative regulator in TNF-alpha
      induced activation of NF-kappaB via disrupting the interaction of TAK1 with
      IKKbeta.

PMID- 25946972
TI  - Autophagy and its function in radiosensitivity.
AB  - Autophagy differs from apoptosis and is independent of phagocytes by the
      appearance of autophagosomes, autolysosomes, and complete nuclei in the cell.
      This process significantly contributes to the antineoplastic effects of
      radiation. Radiation is an important strategy in cancer treatment; however, many
      types of cancer show radioresistance. The effects of radiotherapy are affected by
      factors, including the degree of tumor tissue hypoxia, the ability to repair DNA
      damage, and the presence of cancer stem cells. We review the relationships among
      autophagy, the three factors in cancer radiation, and the possible underlying
      molecular mechanisms. The therapeutic implications of these relationships and
      mechanisms in clinical settings are also discussed.

PMID- 25946973
TI  - CMTM3 inhibits cell growth and migration and predicts favorable survival in oral
      squamous cell carcinoma.
AB  - Downregulation of CKLF-like MARVEL transmembrane domain-containing member 3
      (CMTM3) has been reported in a number of human tumors. However, the role of CMTM3
      in oral squamous cell carcinoma (OSCC) remains largely unknown. In this study, we
      showed that the expression of CMTM3 was significantly reduced in OSCC cell lines
      and primary tumor specimens (P < 0.001). Methylation-specific PCR showed
      hypermethylation in CMTM3 promoter in a significant proportion of tumor tissues
      (61 %). The expression of CMTM3 was associated with T stage, lymph node
      metastasis, tumor node metastasis (TNM) stage, and recurrence of OSCC patients (P
      < 0.05, n = 201). More importantly, CMTM3 expression was associated with the
      prognosis of OSCC patients (P < 0.001) and was an independent prognostic factor
      (hazard ratio = 0.593, 95 % confidence interval, 0.272-1.292; P = 0.039).
      Overexpression of CMTM3 inhibited the growth and migration of OSCC cells. In vivo
      experiments also showed that the growth of OSCC xenografts in nude mice was
      significantly inhibited by CMTM3 overexpression. These findings indicate that
      downregulation of CMTM3 due to promoter hypermethylation contributed to the
      proliferation and migration of OSCC cells and suggest that CMTM3 is an
      independent prognostic factor for the evaluation of the survival of OSCC
      patients.

PMID- 25946974
TI  - Nicotinamide phosphorybosiltransferase overexpression in thyroid malignancies and
      its correlation with tumor stage and with survivin/survivin DEx3 expression.
AB  - Nicotinamide phosphorybosiltransferase (NAMPT) plays an important role in the
      regulation of cellular growth, angiogenesis, and apoptosis in mammalian cells.
      NAMPT overexpression has been recently found in colorectal, breast, prostatic,
      gastric, esophageal, pancreatic cancers, and specific NAMPT inhibitors might be
      adjuvant therapeutic modalities. In this study, we analyzed NAMPT expression in
      40 malignant and in 67 benign thyroid tissue samples using qPCR. We also
      investigated relationships between NAMPT expression and survivin/survivin
      splicing variants DEx3 and 2B expressions. NAMPT expression was significantly
      higher in thyroid cancers (P < 0.0001), and it was positively correlated with
      tumor stage (P = 0.0012; r = 0.493). NAMPT expression was significantly higher in
      tumors staged pT3 or pT4 (16 cases) than in tumors staged pT1 or pT2 (24 cases)
      (P = 0.0106). Metastases to the lymph nodes were found in 12 out of 40 cases, and
      NAMPT expression was higher in the metastatic group (P = 0.0258). Multifocality
      was not associated with higher NAMPT expression (P = 0.3451). NAMPT expression in
      thyroid cancers significantly correlated with survivin and with survivin splice
      variant DEx3 expressions (P < 0.0001; r = 0.624 and P = 0.0239; r = 0.357,
      respectively). There was no correlation between NAMPT and survivin 2B expressions
      (P = 0.3508). This is the first study demonstrating NAMPT overexpression in
      thyroid malignancies using quantitative RT-PCR. Moreover, it shows that NAMPT is
      upregulated in patients with more advanced tumor stage and metastatic disease
      which may prove to be clinically relevant. Further studies are needed to explain
      the role of NAMPT in thyroid cancer biology and the possible use of NAMPT
      inhibitors in thyroid cancer.

PMID- 25946976
TI  - Seawater Incursion Events in a Cretaceous Paleo-lake Revealed by Specific Marine
      Biological Markers.
AB  - Many large paleo-lakes in North China were formed after the Triassic Era.
      Seawater incursion events (SWIEs) in these lakes have been extensively discussed
      in the literature, yet lack reliable methodology and solid evidence, which are
      essential for reconstructing and confirming SWIEs. The present study employs
      specific marine biological markers (24-n-propyl and 24-isopropyl cholestanes) to
      trace SWIEs in a dated core taken from the Songliao Basin (SLB). Two SWIEs were
      identified. The first SWIE from 91.37 to 89.00 Ma, was continuous and variable
      but not strong, while the second SWIE from 84.72 to 83.72 Ma was episodic and
      strong. SWIEs caused high total organic carbon (TOC) and negative delta(13)Corg
      values in the sediments, which were interpreted as an indication of high
      productivity in the lake, due to the enhancement of nutrient supplies as well as
      high levels of aqueous CO2, due to the mixing of alkaline seawater and acidic
      lake water. The SWIEs in SLB were controlled by regional tectonic activity and
      eustatic variation. Movement direction changes of the Izanagi/Kula Plate in 90 Ma
      and 84 Ma created faults and triggered SWIEs. A high sea level, from 90 to 84 Ma,
      also facilitated the occurrence of SWIEs in SLB. 

PMID- 25946975
TI  - Association of SIRT1 and tumor suppressor gene TAp63 expression in head and neck
      squamous cell carcinoma.
AB  - Expression of the protein deacetylase SIRT1 is associated with either poor or
      favorable prognosis in cancer patients, depending on the cancer type. In head and
      neck squamous cell carcinoma (HNSCC), SIRT1 expression is associated with
      favorable prognosis. However, the molecular mechanism underlying the tumor
      suppressive function of SIRT1 in HNSCC is unknown. SIRT1 promotes differentiation
      in epithelial cells; therefore, we investigated whether SIRT1 promotes
      differentiation in HNSCC cells by studying the correlations between the
      expression of SIRT1 and several genes implicated in stemness or differentiation
      in HNSCC-derived cell lines. Our results suggest that SIRT1 does not contribute
      to differentiation in HNSCC cells. RNA interference-mediated reduction of SIRT1
      revealed that SIRT1 supports the expression of TAp63, which has been implicated
      in tumor suppression, in addition to epithelial differentiation. A positive
      correlation was observed between SIRT1 and TAp63 expression in HNSCC tissues, as
      determined by quantitative reverse transcription-polymerase chain reaction
      analysis of RNA extracted from formalin-fixed paraffin-embedded biopsy samples.
      Together, these results suggest that although SIRT1 does not regulate
      differentiation of HNSCC cells, it functions as a tumor suppressor in HNSCC by
      supporting the transcription of tumor-suppressive TAp63. This finding supports
      the notion that SIRT1-activating drugs could be useful for the treatment of
      HNSCC.

PMID- 25946977
TI  - Electrically pumped random lasing based on an Au-ZnO nanowire Schottky junction.
AB  - Electrically pumped random lasing based on an Au-ZnO nanowire Schottky junction
      diode is demonstrated. The device exhibits typical Schottky diode current-voltage
      characteristics with a turn-on voltage of 0.7 V. Electroluminescence
      characterization shows good random lasing behavior and the output power is about
      67 nW at a drive current of 100 mA. Excitonic recombination is responsible for
      lasing generation. Zn plasma is only observed under high applied bias, which can
      be distinguished from the random lasing spectral features near 380 nm. The laser
      diode based on the Schottky junction provides an alternative approach towards
      semiconductor random lasers. 

PMID- 25946978
TI  - Quantitative analysis of marker compounds in Angelica gigas, Angelica sinensis,
      and Angelica acutiloba by HPLC/DAD.
AB  - Although Danggui is the root of Angelica gigas NAKAI in the Korean Pharmacopoeia,
      it is determined that Danggui is also the root of Angelica sinensis (OLIV.) DIELS
      in China and Hong Kong, as well as the root of Angelica acutiloba KITAGAWA in
      Japan. Accordingly, we tried to develop an identification method using the main
      compounds in A. gigas, A. sinensis, and A. acutiloba through HPLC/diode-array
      detector (DAD). This method was fully validated for linearity, accuracy,
      precision, recovery, and robustness. Multivariate analysis was also implemented
      after pattern analysis and monitoring. As a result, each compound pattern of A.
      gigas, A. sinensis, and A. acutiloba was identified, making it possible to
      distinguish them from each other. 

PMID- 25946979
TI  - Conjugation of polymers to proteins through an inhibitor-derived peptide: taking
      up the inhibitor "berth".
AB  - A hexapeptide derived from an enzyme inhibitor was used as an affinity ligand for
      the conjugation of a hydrophilic polymer to the enzyme. The peptide targeted the
      polymer to the "berth" of the inhibitor in the enzyme, affording the enzyme
      resistance to the inhibitor without affecting the enzymatic activity. 

PMID- 25946980
TI  - Enriched Environment Altered Aberrant Hippocampal Neurogenesis and Improved Long
      Term Consequences After Temporal Lobe Epilepsy in Adult Rats.
AB  - Abnormal hippocampal neurogenesis is thought to contribute to cognitive
      impairments in chronic temporal lobe epilepsy (TLE). Stromal cell-derived factor
      1 (SDF-1) and its specific receptor CXCR4 play important roles in neurogenesis.
      We investigated whether enriched environment (EE) might be beneficial for TLE.
      Adult rats were randomly assigned as control rats, rats subjected to status
      epilepticus (SE), or post-SE rats treated with EE for 30 days. We used
      immunofluorescence staining to analyze the hippocampal neurogenesis and Nissl
      staining to evaluate hippocampal damage. Electroencephalography was used to
      measure the duration of spontaneous seizures. Cognitive function was evaluated by
      Morris water maze. Western blot was used to measure the expression of SDF-1 and
      CXCR4 in the hippocampus. In the present study, we found the TLE model resulted
      in aberrant neurogenesis such as reduced proliferation, intensified dendritic
      development of newborn neurons, as well as spontaneous seizures and cognitive
      impairments. More importantly, EE treatment significantly increased the cell
      proliferation and survival, extended the apical dendrites, and delayed the
      attenuation of the expression of SDF-1 and CXCR4, accompanied by decreased long
      term seizure activity and improved cognitive impairments in adult rats after TLE.
      These results provided morphological evidence that EE might be beneficial for
      treating TLE.

PMID- 25946982
TI  - Enhancing the ferromagnetic coupling in extended phloroglucinol complexes by
      increasing the metal SOMO-ligand overlap: synthesis and characterization of a
      trinuclear Co(II)(3) triplesalophen complex.
AB  - The triplesalophen complex [(baron(Me))Co(II)(3)] has been synthesized and
      characterized. The low-spin Co(II) ions possess an (2)A2 ground state with the
      magnetic orbitals of dyz type. These are well oriented for a strong pi overlap
      with the bridging phloroglucinol, which results in the strongest ferromagnetic
      interactions by the spin-polarization mechanism for a 3d phloroglucinol complex.

PMID- 25946981
TI  - Altered Plasticity of Glycogen Phosphorylase in Forebrain Gliosomes Obtained from
      Insulinoma Patients.
AB  - We investigated a control model of hypoglycemia-exposed brain tissues from a
      small series of patients with insulinoma, immediately dissect them, and perform a
      differential cold centrifugation to obtain gliosomes and examine alterations of
      glycogenolytic mechanisms. The BB as well as MM isoforms of glycogen
      phosphorylase enzymatic protein expression remained unaltered between insulinoma
      and control subjects within the gliosomes. However, the glycogen phosphorylase
      remained in a form that was potentially activated several folds on placing the
      gliosomes in a glucose-free medium. This was examined by its increased
      interaction with protein kinase A. Inhibitors of glycogen phosphorylase was used
      as controls. Furthermore, we demonstrated that glucose-depleted medium enhanced
      production of both ATP and lactate by the gliosomes. It is possible that a
      portion of glucose obtained from glycogen breakdown was circuited through
      glycolytic pathways to generate ATP. It has been reported earlier that ATP within
      gliosomes plays a major role in glutamate uptake, thus potentially preventing
      seizure during active bouts of hypoglycemia. Lactate shuttle from astrocytes is a
      potential mechanism to balance neuronal bioenergetics during events of
      hypoglycemia. Newer approaches to pharmacologically modulate glycogen
      phosphorylase may prove to be rational approach for neuroprotective therapy in
      this common clinical syndrome of hypoglycemia. 

PMID- 25946983
TI  - Screening and referral for axial spondyloarthritis--need of the hour.
AB  - Although axial spondyloarthritis (axSpA) is as prevalent as rheumatoid arthritis,
      it is commonly under recognized due to variety of reasons. AxSpA contributes to
      significant loss of function and disability among young adults. With the
      availability of newer assessment methods and effective therapeutic agents, early
      diagnosis and appropriate treatment are possible. As mechanical back pain is
      widely prevalent in general population, selection of patients with high
      likelihood of having axSpA and referral to rheumatologists is very important to
      allow prompt diagnosis and management of axSpA yet avoid improper utilization of
      resources. Various referral strategies have been developed for this purpose which
      have included patients with chronic back pain for >3 months with age of onset <45
      years and one or more typical spondyloarthritis features with high sensitivity
      and specificity. Consistent application of both simple and complex strategies has
      demonstrated similar results in various clinical studies. About 35-45 % of
      patients referred to rheumatologists using these strategies were finally
      diagnosed to have axSpA. Potential referring providers include primary care
      physicians, physical therapists, orthopedic and spine surgeons, chiropractors,
      rehabilitation medicine physicians, ophthalmologists, gastroenterologists, and
      dermatologists. Increasing the awareness and education of the referring providers
      are two very important steps in the success of the referral strategy. With proper
      application of any strategy described below, a rheumatologist will need to see
      two to three patients with chronic back pain to identify one patient with axSpA.

PMID- 25946984
TI  - Cardiac Interventions in Pregnant Patients without Fluoroscopy.
AB  - INTRODUCTION: Cardiac interventions with fluoroscopy during pregnancy carry
      significant risks for the fetus. This report reviews three pregnant patients: two
      of them requiring pacemaker implantation and one underwent diagnostic cardiac
      catheterization without fluoroscopy. METHODS: The cases were performed using
      EnSite system (St. Jude Medical Inc., MN, USA) guidance. The necessary cardiac
      structure geometries were reconstructed with a deflectable quadripolar
      electrophysiology catheter without fluoroscopy. In two cases, pacemaker leads
      were connected to the EnSite system for navigation and fixation of leads. In the
      third case, long sheaths and electrophysiology catheters were used to access the
      right ventricle and pulmonary artery. Transthoracic echocardiography was also
      used in all three cases. RESULTS: A 31-year-old woman at 8-week pregnancy was
      admitted with ventricular septal defect and significant pulmonary hypertension.
      The patient underwent catheterization to assess for the risk of continuation of
      pregnancy. There was partial reactivity, it was decided not to terminate the
      pregnancy, and an uneventful delivery was succeeded at 35 weeks of gestation
      without complications. The rest of the two pregnant patients were a 28-year-old
      pregnant woman at 14 weeks of gestation and a 40-year-old woman at 12-week
      gestation. Both of them presented with symptomatic complete AV block. A single
      chamber pacemaker was implanted in the first one, and a dual-chamber pacemaker
      was implanted in the latter. Pregnancy continued in both without complications.
      CONCLUSION: Successful cardiac catheterization and pacemaker implantation can be
      performed safely in selected pregnant patients using an electroanatomic mapping
      system guidance without fluoroscopy.

PMID- 25946985
TI  - Post-operative arterial thrombosis with non-vitamin K antagonist oral
      anticoagulants after total hip or knee arthroplasty.
AB  - The incidence of post-operative arterial thrombosis (AT) (acute myocardial
      infarction [AMI] and ischaemic stroke) is increased in patients undergoing total
      hip replacement (THR) or total knee replacement (TKR). We compared the incidence
      of post-operative AT in non-vitamin K antagonist oral anticoagulants (NOACs)
      treated and enoxaparin-treated patients, performing a systematic review of phase
      III randomised controlled trials (RCTs) of venous thromboembolism (VTE)
      prophylaxis in THR and TKR. Studies were identified by electronic search of
      MEDLINE and EMBASE database until July 2014. Differences between NOACs and
      enoxaparin groups in the efficacy and safety outcomes were expressed as odds
      ratios (ORs) with pertinent 95 % confidence intervals (95 % CI). Statistical
      heterogeneity was assessed with the I2 statistic. Eleven phase III RCTs for a
      total of 31,319 patients were included. Patients underwent TKR in six studies and
      THR in five studies. The NOACs under study were dabigatran (four studies),
      apixaban (three studies) and rivaroxaban (four studies). AT occurred in 0.23 % of
      patients on NOACs and in 0.27 % of patients on enoxaparin: the OR at fixed-effect
      model was 0.86 (95 % CI 0.53-1.40; I2 11 %). No differences in AT incidence among
      the three NOACs were observed. The incidence of major and clinically relevant
      bleeding was similar in NOACs and enoxaparin groups (OR 1.03, 95 % CI 0.92-1.15;
      I2 38 %). In conclusion, in RCTs of pharmacological VTE prophylaxis in patients
      undergoing THR or TKR, there was no difference in the incidence of post-operative
      AT among patients treated with NOACs, compared to those treated with enoxaparin.

PMID- 25946986
TI  - Modulating the Immune Response Towards a Neuroregenerative Peri-injury Milieu
      After Cerebral Hemorrhage.
AB  - Cerebral hemorrhages account for 15-20 % of stroke sub-types and have very poor
      prognoses. The mortality rate for cerebral hemorrhage patients is between 40 and
      50 %, of which at least half of the deaths occur within the first 2 days, and 75
      % of survivors are incapable of living independently after 1 year. Current
      emergency interventions involve lowering blood pressure and reducing intracranial
      pressure by controlled ventilations or, in the worst case scenarios, surgical
      intervention. Some hemostatic and coagulatherapeutic interventions are being
      investigated, although a few that were promising in experimental studies have
      failed in clinical trials. No significant immunomodulatory intervention, however,
      exists for clinical management of cerebral hemorrhage. The inflammatory response
      following cerebral hemorrhage is particularly harmful in the acute stage because
      blood-brain barrier disruption is amplified and surrounding tissue is destroyed
      by secreted proteases and reactive oxygen species from infiltrated leukocytes. In
      this review, we discuss both the destructive and regenerative roles the immune
      response play following cerebral hemorrhage and focus on microglia, macrophages,
      and T-lymphocytes as the primary agents directing the response. Microglia,
      macrophages, and T-lymphocytes each have sub-types that significantly influence
      the over-arching immune response towards either a pro-inflammatory, destructive,
      or an anti-inflammatory, regenerative, state. Both pre-clinical and clinical
      studies of cerebral hemorrhages that selectively target these immune cells are
      reviewed and we suggest immunomodulatory therapies that reduce inflammation,
      while augmenting neural repair, will improve overall cerebral hemorrhage
      outcomes. 

PMID- 25946988
TI  - Mechanical response of adherent giant liposomes to indentation with a conical AFM
      tip.
AB  - Indentation of giant liposomes with a conical indenter is described by means of a
      tension-based membrane model. We found that nonlinear membrane theory neglecting
      the impact of bending sufficiently describes the mechanical response of liposomes
      to indentation as measured by atomic force microscopy. Giant vesicles are gently
      adsorbed on glassy surfaces via avidin-biotin linkages and indented centrally
      using an atomic force microscope equipped with conventional sharp tips mounted on
      top of an inverted microscope. Force indentation curves display a nonlinear
      response that allows to extract pre-stress of the bilayer T0 and the area
      compressibility modulus KA by computing the contour of the vesicle at a given
      force. The values for KA of fluid membranes correspond well to what is known from
      micropipet suction experiments and inferred from membrane undulation monitoring.
      Assembly of actin shells inside the liposome considerably stiffens the vesicles
      resulting in significantly larger area compressibility modules. The analysis can
      be easily extended to different indenter geometries with rotational symmetry. 

PMID- 25946991
TI  - Two dimensional PMMA nanofluidic device fabricated by hot embossing and oxygen
      plasma assisted thermal bonding methods.
AB  - A method for obtaining a low-cost and high-replication precision two-dimensional
      (2D) nanofluidic device with a polymethyl methacrylate (PMMA) sheet is proposed.
      To improve the replication precision of the 2D PMMA nanochannels during the hot
      embossing process, the deformation of the PMMA sheet was analyzed by a numerical
      simulation method. The constants of the generalized Maxwell model used in the
      numerical simulation were calculated by experimental compressive creep curves
      based on previously established fitting formula. With optimized process
      parameters, 176 nm-wide and 180 nm-deep nanochannels were successfully replicated
      into the PMMA sheet with a replication precision of 98.2%. To thermal bond the 2D
      PMMA nanochannels with high bonding strength and low dimensional loss, the
      parameters of the oxygen plasma treatment and thermal bonding process were
      optimized. In order to measure the dimensional loss of 2D nanochannels after
      thermal bonding, a dimension loss evaluating method based on the nanoindentation
      experiments was proposed. According to the dimension loss evaluating method, the
      total dimensional loss of 2D nanochannels was 6 nm and 21 nm in width and depth,
      respectively. The tensile bonding strength of the 2D PMMA nanofluidic device was
      0.57 MPa. The fluorescence images demonstrate that there was no blocking or
      leakage over the entire microchannels and nanochannels. 

PMID- 25946990
TI  - Digital Health Intervention as an Adjunct to Cardiac Rehabilitation Reduces
      Cardiovascular Risk Factors and Rehospitalizations.
AB  - Cardiac rehabilitation (CR) following myocardial infarction is vastly underused.
      As such, the aim of this study was to test a digital health intervention (DHI) as
      an adjunct to CR. Patients undergoing standard Mayo Clinic CR were recruited
      prior to CR (n = 25) or after 3 months CR (n = 17). Changes in risk factors and
      rehospitalizations plus emergency department (ED) visits were assessed after 3
      months. Patients assigned to DHI during CR had significant reductions in weight (
      4.0 +/- 5.2 kg, P = .001), blood pressure (-10.8 +/- 13.5 mmHg, P = .0009), and
      the group using DHI after 3 months of CR had significant reductions in weight (
      2.5 +/- 3.8 kg, P = .04) and systolic BP (-12.6 +/- 12.4 mmHg, P = .001) compared
      to the control groups. Both DHI groups also displayed significant reductions in
      rehospitalizations/ED visits (-37.9 %, P = 0.01 and -28 %, P = .04,
      respectively). This study suggests that a guideline-driven DHI CR program can
      augment secondary prevention strategies during usual CR by improving risk factors
      for repeat events.

PMID- 25946989
TI  - The Recovery of Hibernating Hearts Lies on a Spectrum: from Bears in Nature to
      Patients with Coronary Artery Disease.
AB  - Clinicians often use the term "hibernating myocardium" in reference to patients
      with ischemic heart disease and decreased function within viable myocardial
      regions. Because the term is a descriptor of nature's process of torpor, we
      provide a comparison of the adaptations observed in both conditions. In nature,
      hearts from hibernating animals undergo a shift in substrate preference in favor
      of fatty acids, while preserving glucose uptake and glycogen. Expression of
      electron transport chain proteins in mitochondria is decreased while antioxidant
      proteins including uncoupling protein-2 are increased. Similarly, hibernating
      hearts from patients have a comparable metabolic signature, with increased
      glucose uptake and glycogen accumulation and decreased oxygen consumption. In
      contrast to nature however, patients with hibernating hearts are at increased
      risk for arrhythmias, and contractility does not fully recover following
      revascularization. Clearly, additional interventions need to be advanced in
      patients with coronary artery disease and hibernating myocardium to prevent
      refractory heart failure. 

PMID- 25946987
TI  - Multiple Sclerosis and T Lymphocytes: An Entangled Story.
AB  - Multiple sclerosis (MS) is the prototypic inflammatory disease of the central
      nervous system (CNS) characterized by multifocal areas of demyelination, axonal
      damage, activation of glial cells, and immune cell infiltration. Despite
      intensive years of research, the etiology of this neurological disorder remains
      elusive. Nevertheless, the abundance of immune cells such as T lymphocytes and
      their products in CNS lesions of MS patients supports the notion that MS is an
      immune-mediated disorder. An important body of evidence gathered from MS animal
      models such as experimental autoimmune encephalomyelitis (EAE), points to the
      central contribution of CD4 T lymphocytes in disease pathogenesis. Both Th1
      (producing interferon-gamma) and Th17 (producing interleukin 17) CD4 T
      lymphocytes targeting CNS self-antigens have been implicated in MS and EAE
      pathobiology. Moreover, several publications suggest that CD8 T lymphocytes also
      participate in the development of MS lesions. The migration of activated T
      lymphocytes from the periphery into the CNS has been identified as a crucial step
      in the formation of MS lesions. Several factors promote such T cell extravasation
      including: molecules (e.g., cell adhesion molecules) implicated in the T cell
      blood brain barrier interaction, and chemokines produced by neural cells.
      Finally, once in the CNS, T lymphocytes need to be reactivated by local antigen
      presenting cells prior to enter the parenchyma where they can initiate damage.
      Further investigations will be necessary to elucidate the impact of environmental
      factors (e.g., gut microbiota) and CNS intrinsic properties (e.g., microglial
      activation) on this inflammatory neurological disease. 

PMID- 25946992
TI  - Intraorbital haematoma during a commercial flight: a case report.
AB  - BACKGROUND: Intraorbital haematoma is a rare clinical entity which can be caused
      by orbital traumas, neoplasms, surgeries nearby sinuses and orbit, vascular
      malformations, acute sinusitis, systemic abnormalities, barotrauma and valsalva
      maneuver. CASE PRESENTATION: A 74-year-old male presented with sudden onset of
      ocular pain, upper eye lid swelling, proptosis and diplopia after a commercial
      flight. After complete ophthalmic ocular examination including pupillary light
      reflexes and laboratory examinations; computed tomography and magnetic resonance
      imaging of orbit revealed a subperiostal mass-like lesion in the right
      retrobulbar-extraconal region which was compatible with intraorbital haematoma.
      Visual acuity was not compromised so we planned a conservative approach with
      close observation. We administered systemic corticosteroid and topical
      dorzolamide/timolol combination therapy. At the first month follow-up,
      intraorbital haematoma resolved without significant sequelae. CONCLUSION:
      Intraorbital haematoma can be managed by conservative approach without any
      intervention if it does not threat visual acuity or optic nerve. We experienced a
      case of intraorbital haematoma during a commercial flight. We discussed the
      rarity of this condition and its management.

PMID- 25946993
TI  - Recreational Snow-Sports Injury Risk Factors and Countermeasures: A Meta-Analysis
      Review and Haddon Matrix Evaluation.
AB  - BACKGROUND: Snow sports (alpine skiing/snowboarding) would benefit from easily
      implemented and cost-effective injury prevention countermeasures that are
      effective in reducing injury rate and severity. OBJECTIVE: For snow sports, to
      identify risk factors and to quantify evidence for effectiveness of injury
      prevention countermeasures. METHODS: Searches of electronic literature databases
      to February 2014 identified 98 articles focused on snow sports that met the
      inclusion criteria and were subsequently reviewed. Pooled odds ratios (ORs) with
      90% confidence intervals (CIs) and inferences (percentage likelihood of
      benefit/harm) were calculated using data from 55 studies using a spreadsheet for
      combining independent groups with a weighting factor based on quality rating
      scores for effects. RESULTS: More experienced skiers and snowboarders are more
      likely to sustain an injury as a result of jumps, while beginners sustain
      injuries primarily as a result of falls. Key risk factors that countermeasure
      interventions should focus on include, beginner skiers (OR 2.72; 90% CI 2.15
      3.44, 99% most likely harmful), beginner snowboarders (OR 2.66; 90% CI 2.08-3.40,
      99% harmful), skiers/snowboarders who rent snow equipment (OR 2.58; 90% CI 1.98
      3.37, 99% harmful) and poor visibility due to inclement weather (OR 2.69; 90% CI
      1.43-5.07, 97% harmful). Effective countermeasures include helmets for
      skiers/snowboarders to prevent head injuries (OR 0.58; 90% CI 0.51-0.66, 99% most
      likely beneficial), and wrist guards for snowboarders to prevent wrist injuries
      (OR 0.33; 90% CI 0.23-0.47, 99% beneficial). DISCUSSION: The review identified
      key risk factors for snow-sport injuries and evaluated the evidence for the
      effectiveness of existing injury prevention countermeasures in recreational
      (general public use of slopes, not racing) snow sports using a Haddon's matrix
      conceptual framework for injury causation (host/snow-sport participant,
      agent/mechanism and environment/community). CONCLUSION: Best evidence for the
      effectiveness of injury prevention countermeasures in recreational snow sports
      was for the use of helmets and wrist guards and to address low visibility issues
      via weather reports and signage.

PMID- 25946995
TI  - Abstracting the principles of development using imaging and modeling.
AB  - Here we look at modern developmental biology with a focus on the relationship
      between different approaches of investigation. We argue that direct imaging is a
      powerful approach not only for obtaining descriptive information but also for
      model generation and testing that lead to mechanistic insights. Modeling, on the
      other hand, conceptualizes imaging data and provides guidance to perturbations.
      The inquiry progresses most efficiently when a trinity of approaches-quantitative
      imaging (measurement), modeling (theory) and perturbation (test)-are pursued in
      concert, but not when one approach is dominant. Using recent studies of the
      zebrafish system, we show how this combination has effectively advanced classic
      topics in developmental biology compared to a perturbation-centric approach.
      Finally, we show that interdisciplinary expertise and perhaps specialization are
      necessary for carrying out a systematic approach, and discuss the technical
      hurdles.

PMID- 25946994
TI  - Creatine Supplementation and Lower Limb Strength Performance: A Systematic Review
      and Meta-Analyses.
AB  - BACKGROUND: Creatine is the most widely used supplementation to increase strength
      performance. However, the few meta-analyses are more than 10 years old and suffer
      from inclusion bias such as the absence of randomization and placebo, the
      diversity of the inclusion criteria (aerobic/endurance, anaerobic/strength), no
      evaluation on specific muscles or group of muscles, and the considerable amount
      of conflicting results within the last decade. OBJECTIVE: The objective of this
      systematic review was to evaluate meta-analyzed effects of creatine
      supplementation on lower limb strength performance. METHODS: We conducted a
      systematic review and meta-analyses of all randomized controlled trials comparing
      creatine supplementation with a placebo, with strength performance of the lower
      limbs measured in exercises lasting less than 3 min. The search strategy used the
      keywords "creatine supplementation" and "performance". Dependent variables were
      creatine loading, total dose, duration, the time-intervals between baseline (T0)
      and the end of the supplementation (T1), as well as any training during
      supplementation. Independent variables were age, sex, and level of physical
      activity at baseline. We conducted meta-analyses at T1, and on changes between T0
      and T1. Each meta-analysis was stratified within lower limb muscle groups and
      exercise tests. RESULTS: We included 60 studies (646 individuals in the creatine
      supplementation group and 651 controls). At T1, the effect size (ES) among
      stratification for squat and leg press were, respectively, 0.336 (95 % CI 0.047
      0.625, p = 0.023) and 0.297 (95 % CI 0.098-0.496, p = 0.003). Overall quadriceps
      ES was 0.266 (95 % CI 0.150-0.381, p < 0.001). Global lower limb ES was 0.235 (95
      % CI 0.125-0.346, p < 0.001). Meta-analysis on changes between T0 and T1 gave
      similar results. The meta-regression showed no links with characteristics of
      population or of supplementation, demonstrating the creatine efficacy effects,
      independent of all listed conditions. CONCLUSION: Creatine supplementation is
      effective in lower limb strength performance for exercise with a duration of less
      than 3 min, independent of population characteristic, training protocols, and
      supplementary doses and duration.

PMID- 25946996
TI  - Recent advances in the genetics of autism spectrum disorder.
AB  - Autism spectrum disorder (ASD) is a devastating neurodevelopmental disorder with
      high prevalence in the population and a pronounced male preponderance. ASD has a
      strong genetic basis, but until recently, a large fraction of the genetic factors
      contributing to liability was still unknown. Over the past 3 years, high
      throughput next-generation sequencing on large cohorts has exposed a
      heterogeneous and complex genetic landscape and has revealed novel risk genes.
      Here, we provide an overview of the recent advances on the ASD genetic
      architecture, with an emphasis on the estimates of heritability, the contribution
      of common variants, and the role of inherited and de novo rare variation. We also
      examine the genetic components of the reported gender bias. Finally, we discuss
      the emerging findings from sequencing studies and how they illuminate crucial
      aspects of ASD pathophysiology.

PMID- 25946998
TI  - Applications of ALD MnO to electrochemical water splitting.
AB  - Atomic layer deposition (ALD) is an attractive method to deposit uniform
      catalytic films onto high surface area electrodes. One interesting material for
      ALD synthesis is MnOx, a promising earth-abundant catalyst for the oxygen
      evolution reaction (OER). It has previously been shown that catalysts beginning
      as MnO synthesized using ALD on smooth glassy carbon (s-GC) electrodes and Mn2O3
      obtained upon annealing MnO on s-GC are active OER catalysts. Here, we use ALD to
      deposit MnO on high surface area GC (HSA-GC) substrates, forming an active
      catalyst on a geometric surface area basis. We then characterize three types of
      catalysts, HSA-GC MnO, s-GC MnO, and annealed MnO (Mn2O3), using cyclic
      voltammetry (CV), scanning electron microscopy (SEM), and ex situ X-ray
      absorption spectroscopy (XAS). We show that under OER conditions, all three
      catalysts oxidize to similar surface states with a mixture of Mn(3+)/Mn(4+) and
      that MnOx surface area effects can account for the observed differences in the
      catalytic activity. We also demonstrate the need for a high surface area support
      for high OER activity on a geometric basis. 

PMID- 25946997
TI  - The I22V and L72S substitutions in West Nile virus prM protein promote enhanced
      prM/E heterodimerisation and nucleocapsid incorporation.
AB  - BACKGROUND: Amino acid substitutions I22V and L72S in the prM protein of West
      Nile virus Kunjin strain (WNVKUN) were previously shown to enhance virus
      secretion and virulence, but a mechanism by which this occurred was not
      determined. FINDINGS: Using pulse-chase experiments followed by co
      immunoprecipitation with anti-E antibody, we demonstrated that the I22V and L72S
      substitutions enhanced prM/E heterodimerization for both the E-glycosylated and E
      unglycosylated virus. Furthermore, analysis of secreted particles revealed that
      I22V and L72S substitutions also enhanced nucleocapsid incorporation.
      CONCLUSIONS: We have demonstrated mechanistically that improved secretion of
      virus particles in the presence of I22V and L72S substitutions was contributed by
      more efficient prM/E heterodimerization.

PMID- 25946999
TI  - Association of peripheral nerve conduction in diabetic neuropathy with
      subclinical left ventricular systolic dysfunction.
AB  - BACKGROUND: Subclinical left ventricular (LV) longitudinal myocardial systolic
      dysfunction occurs in patients with diabetes mellitus (DM) and preserved LV
      ejection fraction (LVEF), and is closely related to DM-related complications.
      However, the association of diabetic neuropathy (DN) with subclinical LV systolic
      longitudinal dysfunction in such patients has not been fully clarified. METHODS:
      The subjects of this study were 112 consecutive DM patients with preserved LVEF
      (all >=50%) without coronary artery disease and overt heart failure (aged 59 +/-
      14 years; 60 women, 52 men). Global longitudinal strain (GLS) was determined as
      the average peak strain of 18 segments from the three standard apical views, and
      was expressed as an absolute value. DN was diagnosed by experienced
      diabetologists. Median, ulnar, and sural nerves were subjected to motor and
      sensory nerve conduction studies. F-wave latency was defined as the minimum F
      wave latency after a total of 16 stimulations of the tibial nerve. RESULTS: Forty
      one (37%) patients were clinically diagnosed with DN. LV functions of DM patients
      with and without DN were similar except for GLS being significantly smaller in
      patients with than in patients without DN (18 +/- 2% vs. 20 +/- 2%, p < 0.001).
      It was noteworthy that, of the parameters for the nerve conduction study, only F
      wave latency correlated with GLS (r = -0.34, p < 0.001), and also was identified
      as an independent determinative value of GLS in a multivariate linear regression
      model (beta = -0.25, p = 0.001) even after adjustment for other closely related
      GLS factors. CONCLUSIONS: Monitoring of F-wave latency may aid early detection of
      not only DN but also subclinical LV dysfunction. Joint planning of assessment by
      diabetologists and cardiologists is therefore advisable for better management of
      DM patients.

PMID- 25947001
TI  - Association Between Basal Thinning of Interventricular Septum and Adverse Long
      Term Clinical Outcomes in Patients With Cardiac Sarcoidosis.
AB  - BACKGROUND: Basal thinning of the interventricular septum (IVS) is an important
      diagnostic feature of cardiac sarcoidosis (CS), but its long-term prognostic
      significance remains unclear. METHODS AND RESULTS: We examined 74 consecutive
      patients who were diagnosed with CS. Basal IVS thickness at a point located 10 mm
      from the aortic annulus was measured. IVS thickness at the left ventricular minor
      axis level (IVS) was also measured according to the recommended procedure of the
      American Society of Echocardiography. Patients were divided into 2 groups based
      on the presence or absence of basal IVS thinning, which was defined as basal IVS
      <=4 mm and/or basal IVS/IVS ratio <=0.6. Basal IVS thinning was observed in 21
      patients and was associated with greater long-term adverse events during follow
      up (5.1+/-2.5 years), although the baseline characteristics were comparable
      between groups (overall, P<0.01; all-cause death, P=0.53; symptomatic
      arrhythmias, P<0.01; heart failure admission, P=0.027). Multivariate analysis
      showed basal IVS thinning was an independent determinant of long-term adverse
      events (hazard ratio 2.86, 95% confidence interval 1.31-6.14) even after
      adjustment for existing prognostic variables. CONCLUSIONS: The presence of basal
      IVS thinning at the time of CS diagnosis was associated with poor long-term
      clinical outcomes, suggesting its prognostic significance in patients with CS.

PMID- 25947002
TI  - Usefulness of a Simple Clinical Risk Prediction Method, Modified ACEF Score, for
      Transcatheter Aortic Valve Implantation.
AB  - BACKGROUND: We assessed the predictive accuracy of a simple risk score, modified
      age, creatinine clearance, ejection fraction (ACEFmodif) score, for outcome of
      transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: We
      prospectively included 703 consecutive patients undergoing TAVI. Patients were
      divided into low, middle and high ACEFmodif tertiles. Increased ACEFmodif score
      was associated with a significantly higher 1-year mortality rate (22%, 28% and
      36%, P<0.01) and higher risk of acute kidney injury (AKI; 10%, 10% and 22%,
      P<0.01). On multivariate logistic regression analysis, ACEFmodif score was the
      only independent predictor of AKI. On multivariate Cox regression, ACEFmodif
      score was an independent predictor of 1-year cumulative mortality. Although the
      area under curve (AUC) showed that all risk scores poorly predicted the incidence
      of AKI and 1-year cumulative mortality, ACEFmodif score was more efficient in
      predicting the incidence of AKI compared with STS, LES and ES II (AUC, 0.61,
      0.55, 0.54, 0.57, respectively). Furthermore, ACEFmodif score had similar
      accuracy in predicting 1-year mortality compared with other risk scores (AUC,
      0.61, 0.61, 0.61, 0.61, respectively). CONCLUSIONS: ACEFmodif score may provide
      useful information for predicting AKI, 30-day and 1-year mortality in patients
      undergoing TAVI, but these results need further confirmation.

PMID- 25947003
TI  - Stored intracardiac electrograms reveal patients with sick sinus syndrome
      frequently develop atrioventricular block.

PMID- 25947004
TI  - Current status and clinical development of transcatheter approaches for severe
      mitral regurgitation.
AB  - Transcatheter mitral valve intervention has emerged as an effective treatment
      option for symptomatic severe mitral regurgitation in patients considered to be
      inoperable or at high operative risk for surgical mitral valve surgery. Most
      transcatheter approaches are modifications of existing surgical approaches.
      Transcatheter edge-to-edge mitral valve repair with the MitraClip system has the
      largest clinical experience to date, as it offers a sustained clinical benefit in
      selected patients. This review aims to provide an up-to-date overview of
      transcatheter mitral valve interventions, including leaflet repair, annuloplasty,
      and mitral valve implantation.

PMID- 25947000
TI  - Comprehensive Risk Stratification of Japanese Patients With Aortic Stenosis--A
      Proposal of a New Risk Score From the CHART-2 Study.
AB  - BACKGROUND: The risk of patients with aortic stenosis (AS) should be stratified
      not only by AS severity but also by comorbidities. METHODS AND RESULTS: We aimed
      to develop a risk score for mortality in 412 patients with AS (pressure gradient
      >=30 mmHg, mean age 74.9 years, male 52.4%) in the CHART-2 Study (n=10,219).
      During a 3-year follow-up, 73 (17.7%) patients died. Crude 3-year mortality of
      patients in New York Heart Association (NYHA) classes I, II, and III/IV was 9.5%,
      16.5%, and 49.7%, respectively (P<0.001). Stepwise Cox regression analysis showed
      that the combination of 7 factors was the best model to predict the mortality of
      AS patients, who were scored according to their hazard ratios, including NYHA
      class III-IV (score 6), male sex (3), serum albumin level <=4 g/dl (2), aortic
      peak flow >=4.5 m/s (2), age >=75 years (2), chronic kidney disease (2), and
      anemia (1). Receiver-operating characteristic analysis showed excellent
      association between the sum of the scores and 3-year mortality (area under the
      curve, 0.78). The multivariate Cox proportional hazard model demonstrated that
      the present risk score also well stratified the mortality risk. CONCLUSIONS: The
      present study demonstrates that, in addition to the classical prognostic factors
      related to symptoms and AS severity, various comorbidities are associated with
      mortality. Thus, the present comprehensive risk score may be useful for risk
      stratification of AS patients.

PMID- 25947005
TI  - An empirical strategy to detect bacterial transcript structure from directional
      RNA-seq transcriptome data.
AB  - BACKGROUND: As sequencing costs are being lowered continuously, RNA-seq has
      gradually been adopted as the first choice for comparative transcriptome studies
      with bacteria. Unlike microarrays, RNA-seq can directly detect cDNA derived from
      mRNA transcripts at a single nucleotide resolution. Not only does this allow
      researchers to determine the absolute expression level of genes, but it also
      conveys information about transcript structure. Few automatic software tools have
      yet been established to investigate large-scale RNA-seq data for bacterial
      transcript structure analysis. RESULTS: In this study, 54 directional RNA-seq
      libraries from Salmonella serovar Typhimurium (S. Typhimurium) 14028s were
      examined for potential relationships between read mapping patterns and transcript
      structure. We developed an empirical method, combined with statistical tests, to
      automatically detect key transcript features, including transcriptional start
      sites (TSSs), transcriptional termination sites (TTSs) and operon organization.
      Using our method, we obtained 2,764 TSSs and 1,467 TTSs for 1331 and 844
      different genes, respectively. Identification of TSSs facilitated further
      discrimination of 215 putative sigma 38 regulons and 863 potential sigma 70
      regulons. Combining the TSSs and TTSs with intergenic distance and co-expression
      information, we comprehensively annotated the operon organization in S.
      Typhimurium 14028s. CONCLUSIONS: Our results show that directional RNA-seq can be
      used to detect transcriptional borders at an acceptable resolution of +/-10-20
      nucleotides. Technical limitations of the RNA-seq procedure may prevent single
      nucleotide resolution. The automatic transcript border detection methods,
      statistical models and operon organization pipeline that we have described could
      be widely applied to RNA-seq studies in other bacteria. Furthermore, the TSSs,
      TTSs, operons, promoters and unstranslated regions that we have defined for S.
      Typhimurium 14028s may constitute valuable resources that can be used for
      comparative analyses with other Salmonella serotypes.

PMID- 25947007
TI  - Clinical solutions: not always what they seem?

PMID- 25947006
TI  - Macrophages and immune cells in atherosclerosis: recent advances and novel
      concepts.
AB  - Atherosclerotic lesion-related thrombosis is the major cause of myocardial
      infarction and stroke, which together constitute the leading cause of mortality
      worldwide. The inflammatory response is considered as a predominant driving force
      in atherosclerotic plaque formation, growth and progression towards instability
      and rupture. Notably, accumulation of macrophages in the intima and emergence of
      a pro-inflammatory milieu are a characteristic feature of plaque progression, and
      these processes can be modulated by adaptive immune responses. Recently, novel
      evidences of onsite proliferation of macrophages in lesions and
      transdifferentiation of smooth muscle cells to macrophages have challenged the
      prevalent paradigm that macrophage accumulation mostly relies on recruitment of
      circulating monocytes to plaques. Furthermore, previously unrecognized roles of
      inflammatory cell subsets such as plasmacytoid dendritic cells, innate response
      activator B cells or CD8(+) T cells in atherosclerosis have emerged, as well as
      novel mechanisms by which regulatory T cells or natural killer T cells contribute
      to lesion formation. Here, we review and discuss these recent advances in our
      understanding of inflammatory processes in atherosclerosis. 

PMID- 25947008
TI  - Recurrence of Merkel cell carcinoma in the gastrointestinal tract: a case report.
AB  - BACKGROUND: Merkel cell carcinoma is a rare and aggressive skin malignancy that
      arises from primary neural cells and has a tendency for local recurrence and
      regional lymph node metastases. There are only a few cases in the literature
      reporting metastases of Merkel cell carcinoma to the gastrointestinal tract. CASE
      PRESENTATION: We present a 70 year old Caucasian female with distant history of
      Merkel cell carcinoma who presented with iron-deficiency anemia. Colonoscopy
      performed later for the evaluation of anemia revealed 1 cm polyp in ascending
      colon which turned out to be the recurrence of Merkel cell carcinoma. CONCLUSION:
      Metastatic Merkel cell carcinoma to the gastrointestinal tract or any other organ
      should be considered in patients with a history of Merkel cell carcinoma.

PMID- 25947009
TI  - Contributory factors to patient safety incidents in primary care: protocol for a
      systematic review.
AB  - BACKGROUND: Organisations need to systematically identify contributory factors
      (or causes) which impact on patient safety in order to effectively learn from
      error. Investigations of error have tended to focus on taking a reactive approach
      to learning from error, mainly relying on incident-reporting systems. Existing
      frameworks which aim to identify latent causes of error rely almost exclusively
      on evidence from non-healthcare settings. In view of this, the Yorkshire
      Contributory Factors Framework (YCFF) was developed in the hospital setting.
      Eighty-five percent of healthcare contacts occur in primary care. As a result,
      this review will build on the work that produced the YCFF, by examining the
      empirical evidence that relates to the contributory factors of error within a
      primary care setting. METHODS/DESIGN: Four electronic bibliographic databases
      will be searched: MEDLINE, Embase, PsycInfo and CINAHL. The database search will
      be supplemented by additional search methodologies including citation searching
      and snowballing strategies which include reviewing reference lists and reviewing
      relevant journal table of contents, that is, BMJ Quality and Safety. Our search
      strategy will include search combinations of three key blocks of terms. Studies
      will not be excluded based on design. Included studies will be empirical studies
      conducted in a primary care setting. They will include some description of the
      factors that contribute to patient safety. One reviewer (SG) will screen all the
      titles and abstracts, whilst a second reviewer will screen 50% of the abstracts.
      Two reviewers (SG and AH) will perform study selection, quality assessment and
      data extraction using standard forms. Disagreements will be resolved through
      discussion or third party adjudication. Data to be collected include study
      characteristics (year, objective, research method, setting, country), participant
      characteristics (number, age, gender, diagnoses), patient safety incident type
      and characteristics, practice characteristics and study outcomes. DISCUSSION: The
      review will summarise the literature relating to contributory factors to patient
      safety incidents in primary care. The findings from this review will provide an
      evidence-based contributory factors framework for use in the primary care
      setting. It will increase understanding of factors that contribute to patient
      safety incidents and ultimately improve quality of health care.

PMID- 25947010
TI  - A 12-month, moderate-intensity exercise training program improves fitness and
      quality of life in adults with asthma: a controlled trial.
AB  - BACKGROUND: Physical training has been shown to improve exercise capabilities in
      patients with asthma. Most studies focused on children and younger adults.
      Previously, the maximum program duration was six months. It is not known whether
      the same results may be obtained with lower intensity programs and sustained for
      time periods longer than 6 months. This controlled study was undertaken to
      investigate the effects of a moderate intensity outpatient training program of
      one year duration on physical fitness and quality of life in adults with asthma.
      METHODS: 21 adult asthmatics (mean age 56 +/- 10 years) were allocated to
      outpatient training (n = 13) or standard care (n = 8). Exercise consisted of once
      weekly, 60-minute sessions of moderate intensity. Assessments at baseline and
      after one year included cardiopulmonary exercise testing and Short Form-36 and
      Asthma Quality of Life Questionnaires. RESULTS: Following one year of exercise,
      relevant improvements were observed in the training group for maximum work
      capacity (p = 0.005), peak oxygen uptake (p < 0.005), O2pulse (p < 0.05), maximum
      ventilation (p < 0.005), and most of the quality of life domains. No changes were
      observed in the control group. CONCLUSIONS: A physiotherapist-led, long-term,
      moderate-intensity exercise program of one year duration can induce clinically
      relevant improvements in exercise capabilities and health-related quality of life
      in well-motivated adults with asthma. TRIAL REGISTRATION: clinicaltrials.gov
      NCT01097473 . Date trial registered: 31.03.2010.

PMID- 25947011
TI  - Neighborhood Disadvantage and Adolescent Substance Use Disorder: The Moderating
      Role of Maltreatment.
AB  - The ecological-transactional model proposes that nested contexts interact to
      influence development. From this perspective, child maltreatment represents an
      individual-level risk factor posited to interact with numerous other nested
      contextual levels, such as the neighborhood environment, to affect development.
      The aim of this study was to investigate whether adolescents with maltreatment
      histories represent a vulnerable group for whom disadvantaged neighborhoods
      confer risk for substance use disorders. Participants were 411 adolescents (age
      15-18; mean age = 16.24) from an investigation of the developmental sequelae of
      childhood maltreatment. Multiple-group structural equation models, controlling
      for family-level socioeconomic status, indicated that neighborhood disadvantage
      was associated with more marijuana-dependence symptoms among maltreated but not
      among non-maltreated adolescents. Moreover, among maltreated adolescents, those
      who experienced multiple subtypes of maltreatment were at greatest risk for
      problematic marijuana use in the context of neighborhood disadvantage.
      Interestingly, the direct effect of neighborhood disadvantage, but not the
      interaction with maltreatment, was related to adolescent alcohol-dependence
      symptoms. Results highlight the importance of considering multiple levels of
      influence when examining risk associated with child maltreatment. 

PMID- 25947012
TI  - Knowledge, Behavioral, and Sociocultural Factors Related to Human Papillomavirus
      Infection and Cervical Cancer Screening Among Inner-City Women in Panama.
AB  - Cervical cancer remains a leading cause of mortality in developing countries
      regardless of biomedical advances in prevention modalities. Specifically, Panama
      experiences one of the highest rates of cervical cancer worldwide. The objective
      of this study was to explore knowledge, behavioral, and sociocultural factors
      related to cervical cancer prevention among Panamanian women. A theory-guided,
      population-based quantitative survey following participatory processes was
      administered to a randomized sample of females (18-44 years) residing in a high
      risk Panamanian community. Participants (n = 324) reported low knowledge
      regarding HPV, cervical cancer, and the purpose of the Pap test. Furthermore, low
      perceived susceptibility, high-risk sexual behaviors (e.g., low contraception and
      condom use) and adverse attitudes toward the Pap test (e.g., shame, fear) were
      identified. Television, newspapers/magazines, and relatives/friends/neighbors
      were common sources to receive health information. Significant gaps in knowledge
      and behavioral factors were identified, which may interfere with cervical cancer
      prevention efforts. Future strategies should reflect the sociocultural context,
      such as interpersonal relations, when developing and implementing cervical cancer
      programs, with the ultimate goal of decreasing the persistent burden among Latin
      American women.

PMID- 25947015
TI  - How Europe keeps migrants out of its health system.

PMID- 25947013
TI  - Increased expression of Solute carrier family 12 member 5 via gene amplification
      contributes to tumour progression and metastasis and associates with poor
      survival in colorectal cancer.
AB  - OBJECTIVE: Using whole genome sequencing, we identified gene amplification of
      solute carrier family 12 member 5 (SLC12A5) located at 20q13.12 in colorectal
      cancer (CRC). We analysed its amplification, overexpression, biological effects
      and prognostic significance in CRC. DESIGN: SLC12A5 amplification status was
      evaluated by fluorescence in situ hybridisation (FISH). The effects of SLC12A5 re
      expression or knockdown were determined in proliferation, apoptosis, invasion and
      metastasis assays. SLC12A5 target genes and related pathways were identified by
      reporter activity and cDNA microarray analyses. Clinical impact of SLC12A5
      overexpression was assessed in 195 patients with CRC. RESULTS: Amplification of
      SLC12A5 was verified in 78 out of 191 (40.8%) patients with primary CRC by FISH,
      which was positively correlated with its protein overexpression (p<0.001).
      Biofunctional investigation of SLC12A5 revealed that SLC12A5 significantly
      increased cell proliferation, G1-S cell cycle transition, invasion/migration
      abilities, but suppressed apoptosis in vitro and promoted xenograft tumour growth
      as well as lung metastasis in vivo. The antiapoptosis effect by SLC12A5 was
      mediated through inhibiting apoptosis-inducing factor and endonuclease G
      dependent apoptotic signalling pathway; and the pro-metastasis role was by
      regulating key elements of the matrix architecture, including matrix
      metallopeptidase and fibronectin. After a median follow-up of 50.16 months,
      multivariate analysis revealed that patients with SLC12A5 protein overexpression
      had a significant decrease in overall survival. Kaplan-Meier survival curves
      showed that SLC12A5 overexpression was significantly associated with shortened
      survival in patients with CRC. CONCLUSIONS: SLC12A5 plays a pivotal oncogenic
      role in colorectal carcinogenesis; its overexpression is an independent
      prognostic factor of patients with CRC.

PMID- 25947014
TI  - High- and Low-Order Overtaking-Ability Affordances: Drivers Rely on the Maximum
      Velocity and Acceleration of Their Cars to Perform Overtaking Maneuvers.
AB  - OBJECTIVE: The aim of this study was to answer the question, Do drivers take into
      account the action boundaries of their car when overtaking? BACKGROUND: The
      Morice et al. affordance-based approach to visually guided overtaking suggests
      that the "overtake-ability" affordance can be formalized as the ratio of the
      "minimum satisfying velocity" (MSV) of the maneuver to the maximum velocity
      (V(max)) of the driven car. In this definition, however, the maximum acceleration
      (A(max)) of the vehicle is ignored. We hypothesize that drivers may be sensitive
      to an affordance redefined with the ratio of the "minimum satisfying
      acceleration" (MSA) to the A(max) of the car. METHOD: Two groups of nine drivers
      drove cars differing in their A(max). They were instructed to attempt overtaking
      maneuvers in 25 situations resulting from the combination of five MSA and five
      MSV values. RESULTS: When overtaking frequency was expressed as a function of MSV
      and MSA, maneuvers were found to be initiated differently for the two groups.
      However, when expressed as a function of MSV/V(max) and MSA/A(max), overtaking
      frequency was quite similar for both groups. Finally, a multiple regression
      coefficient analysis demonstrated that overtaking decisions are fully explained
      by a composite variable comprising MSA/A(max) and the time required to reach MSV.
      CONCLUSION: Drivers reliably decide whether overtaking is safe (or not) by using
      low- and high-order variables taking into account their car's maximum velocity
      and acceleration, respectively, as predicted by "affordance-based control"
      theory. APPLICATION: Potential applications include the design of overtaking
      assistance, which should exploit the MSA/A(max) variables in order to suggest
      perceptually relevant overtaking solutions.

PMID- 25947016
TI  - [Nationwide survey of acute liver failure according to the definition and
      classification in Japan].

PMID- 25947017
TI  - [Prediction of hepatic encephalopathy development in acute liver injury].

PMID- 25947018
TI  - [Treatment of acute liver failure in Japan].

PMID- 25947019
TI  - [Outcome prediction system for patients with acute liver failure].

PMID- 25947020
TI  - [A case of adenosquamous carcinoma at the esophagogastric junction, initially
      diagnosed as collision carcinoma].
AB  - A 47-year-old man was found to have a type 2 tumor of the esophagogastric
      junction on upper gastrointestinal endoscopy. Biopsy specimens revealed squamous
      cell carcinoma of the esophagus and adenocarcinoma of the stomach. The
      preoperative diagnosis was a collision carcinoma. No distant metastases were
      identified on computed tomography; therefore, partial esophagectomy and
      gastrectomy were performed. Pathological examination of the resected specimen
      revealed adenosquamous carcinoma at the esophagogastric junction (TNM
      classification: stage IIA, T3N0M0). Adenosquamous cell carcinoma of the esophagus
      and stomach is rare, but that at the esophagogastric junction even rarer. 

PMID- 25947021
TI  - [A case of Hamman's syndrome associated with acute-onset type 1 diabetes mellitus
      presenting with abdominal pain].
AB  - A 21-year-old female presented at an emergency department with abdominal pain and
      nausea. Computed tomography (CT) of the chest and abdomen revealed a small amount
      of mediastinal emphysema in the precardiac area, but the underlying cause could
      not be identified. On admission, her plasma glucose was 371 mg/dl, glycated
      hemoglobin (HbA1c) was 14.0%, and blood pH was 6.91. These findings supported a
      diagnosis of Hamman's syndrome associated with diabetic ketoacidosis. Her
      diabetic ketoacidosis was managed with insulin and fluid therapy, and the
      mediastinal emphysema disappeared spontaneously by the time of discharge.
      Presence of free air of the chest and abdominal cavity must warrant a
      differential diagnosis of gastrointestinal perforation; however, when the free
      air is accompanied by diabetic ketoacidosis, it is not necessary to perform
      urgent endoscopy. 

PMID- 25947022
TI  - [A case of enterolith ileus secondary to acute pancreatitis associated with a
      juxtapapillary duodenal diverticulum].
AB  - A 63-year-old woman with abdominal pain was referred to our hospital. Her
      pancreatic enzymes were elevated, and an abdominal computed tomography (CT) scan
      showed an enlarged pancreas, consistent with pancreatitis, and gas collection
      containing an impacted stone adjacent to Vater's papilla. This finding raised the
      suspicion of a duodenal diverticulum. A subsequent ERCP showed a juxtapapillary
      duodenal diverticulum (JPDD) filled with calculi and pus. The pancreatitis
      improved with 2 weeks of conservative treatment. Subsequently, the patient
      underwent resection of the uterus and bilateral adnexa to remove a large ovarian
      cyst that was also identified on the admission CT scan. On the third
      postoperative day, she developed abdominal pain and vomiting. CT revealed small
      bowel obstruction caused by an enterolith expelled from JPDD. Enterotomy was
      performed to remove the stone. To our knowledge, only three similar cases have
      been previously reported in Japan. 

PMID- 25947023
TI  - [A clinical study of fulminant amebic colitis].
AB  - The administration of metronidazole is generally effective to treat amebic
      colitis. Fulminant amebic colitis is relatively rare, and it is associated with a
      high mortality rate. Three cases of fulminant amebic colitis were diagnosed in
      our hospital between 1993 and 2014. One of these patients died despite our
      efforts. Amebic colitis often presents with no obvious risk factors and with
      atypical clinical symptoms. Therefore, the diagnosis of amebic colitis can be
      difficult. Early diagnosis is the most important factor in successful treatment
      of fulminant amebic colitis. The present cases demonstrate that it is important
      to consider the possibility of amebic colitis during evaluation of the acute
      abdomen. 

PMID- 25947024
TI  - [Hepatic mucosa-associated lymphoid tissue lymphoma in a patient with chronic
      hepatitis B].
AB  - A 50-year-old woman with chronic hepatitis associated with hepatitis B virus was
      found to have a hypoechoic liver tumor of 20 mm in diameter on ultrasonography.
      Dynamic computed tomography and magnetic resonance imaging revealed multiple
      tumors in the liver. The portal vein passed through the tumor, which is not a
      typical feature of hepatocellular carcinoma. We subsequently performed tumor
      biopsy and diagnosed mucosa-associated lymphoid tissue (MALT) lymphoma of hepatic
      origin. Here we report this rare case of hepatic MALT lymphoma in a patient with
      chronic hepatitis B, and present a review of the literature. 

PMID- 25947025
TI  - [A case of secondary sclerosing cholangitis caused by chemotherapy with nab
      paclitaxel].
AB  - A 73-year-old woman had received 9 months of chemotherapy with nab-paclitaxel for
      locally advanced breast cancer. During the treatment, she was well and showed no
      major side effects except for alopecia and arthralgia. The tumor showed a
      tendency to reduction. However, chemotherapy was discontinued because of liver
      dysfunction. MRCP and ERCP demonstrated multiple stenoses of the hepatic ducts
      and the intrahepatic bile ducts. We diagnosed chemotherapy-induced sclerosing
      cholangitis caused by nab-paclitaxel. Treatment with ursodeoxycholic acid and
      steroid was ineffective. We added bezafibrate, which resulted in a gradual
      improvement in liver function. To the best of our knowledge, this is the first
      reported case of nab-paclitaxel-induced secondary sclerosing cholangitis. 

PMID- 25947026
TI  - [Two cases of squamoid cyst of the pancreatic ducts].
AB  - Two patients were referred to our hospital with cystic lesion (diameter 5 cm) of
      the pancreas and elevated serum CEA and CA19-9. We diagnosed them with malignant
      cystic neoplasms of the pancreas and performed distal pancreatectomy.
      Histologically, in both cases the cysts were lined with flat, transitional,
      squamoid cells without keratinization. Immunohistochemical staining confirmed two
      rare cases of squamoid cyst of the pancreatic ducts. 

PMID- 25947028
TI  - Healthcare transformation and the need for courageous leadership.

PMID- 25947027
TI  - [Nonalcoholic steatohepatitis after pancreatoduodenectomy with rapid progression
      of hepatic fibrosis: a case report].
AB  - A 64-year-old woman who had undergone pancreatoduodenectomy for intraductal
      papillary mucinous carcinoma 10 months previously was referred to our department
      complaining of ascites and general malaise. Abdominal computed tomography (CT)
      showed a markedly decreased hepatic CT value. Liver biopsy revealed nonalcoholic
      steatohepatitis. Treatment with nutritional control and pancreatic enzyme
      supplements improved liver function. Exocrine pancreatic enzyme insufficiency
      from chronic pancreatitis is considered to be a cause of rapid progression of
      hepatic steatosis. 

PMID- 25947029
TI  - Researcher Patricia Martens turned dry data into stories.

PMID- 25947031
TI  - Towards reconciliation of several dualities in physician leadership.
AB  - Leadership has a renewed focus in healthcare, and physicians are being
      increasingly involved in a range of leadership roles. The aim of this paper is to
      discuss several dualities that exert tensions at the systems and individual
      levels. Although oppositional, the common dualities of physician leadership are
      not mutually exclusive but represent a complex, dynamic and interdependent
      relationship, often coexisting with each other and exerting tensions in multiple
      dimensions. The authors contend that a dialectic understanding--instead of
      either/or or finding a middle ground--of the opposite poles of these dualities
      allows for generating meaningful leadership perspectives and choices.

PMID- 25947030
TI  - Dummheit.
AB  - Immunizing against influenza is tricky; against measles is not. Influenza comes
      in many constantly evolving strains, but one measles shot in childhood confers
      lifelong immunity. Unlike the flu, measles was wiped out. Its return represents
      an outbreak not of disease, but of stupidity. The matrix of stupidity is,
      however, reinforced by strong strands of malice, as when Andrew Wakefield's
      fraudulent 1998 paper linked the MMR vaccine to autism. The fraud was unmasked
      and the vaccine-autism link disproven, but the evil influence continues. Measles
      offers an illustration of Virchow's insights that medicine is a social science
      and that politics is medicine writ large. It is this "inconvenient truth" that is
      being suppressed by muzzling the Chief Public Health Officer (CPHO) and attacking
      public health for addressing "social determinants." 

PMID- 25947032
TI  - Quality of physiotherapy services for injured workers compensated by workers'
      compensation in Quebec: a focus group study of physiotherapy professionals.
AB  - Musculoskeletal disorders are among the leading causes of work-related physical
      disability in the province of Quebec in Canada. The authors conducted a focus
      group study with physiotherapists and physical rehabilitation therapists working
      with patients whose treatments are compensated by the Quebec Workers'
      Compensation Board with the goal of exploring quality of care and ethical issues.
      Three main themes were identified: (1) systemic factors, (2) complexity in
      treatment decisions and (3) inequality of care. Although physiotherapy
      professionals strive to give these patients the best possible care, patients
      might not always be provided with optimal or equal treatment. When compared with
      other patients, there appear to be differences with respect to access to care and
      types of services offered to injured workers, raising equity concerns. Factors
      that shape and constrain quality of physiotherapy services for injured workers
      need to be addressed to improve care for these patients. 

PMID- 25947033
TI  - Barriers and facilitators to family planning access in Canada.
AB  - BACKGROUND: Contraceptives are underutilized in Canada, and nearly one in three
      Canadian women will have an abortion in her lifetime. To help delineate a
      national family planning research agenda, the authors interviewed healthcare
      providers and organizational stakeholders to explore their perspective on
      barriers to contraception across regions of Canada. METHODS: Semi-structured
      interviews were conducted based on validated frameworks for assessing family
      planning access and quality. The authors purposefully selected 14 key
      stakeholders from government agencies, professional organizations and non
      governmental organizations for in-person interviews. Fifty-eight healthcare
      providers and representatives of stakeholder organizations in reproductive health
      who self-selected through an online survey were also interviewed. Transcripts
      were analyzed for repeated and saturated themes. RESULTS: Cost was the most
      important barrier to contraception. Sexual health education was reported as
      inconsistent, even within provinces. Regional differences were highlighted,
      including limited access to family physicians in rural Canada and throughout
      Quebec. Physician bias and outdated practices were cited as significant barriers
      to quality. New immigrants, youth, young adults and women in small rural,
      Northern and Aboriginal communities were all identified as particularly
      vulnerable. Informants identified multiple opportunities for health policy and
      system restructuring, including subsidized contraception, and enhancing public
      and healthcare provider education. Sexual health clinics were viewed as a highly
      successful model. Task-sharing and expanded scope of practice of nurses, nurse
      practitioners and pharmacists, alongside telephone and virtual healthcare
      consultations, were suggested to create multiple points of entry into the system.
      CONCLUSION: Results underscore the need for a national strategic approach to
      family planning health policy and health services delivery in Canada.

PMID- 25947035
TI  - Favorable prognostic impact of RAS mutation status in multiple myeloma treated
      with high-dose melphalan and autologous stem cell support in the era of novel
      agents: a single center perspective.

PMID- 25947034
TI  - Use of Compassionate Supply of Antiretroviral Drugs to Avoid Treatment
      Interruptions or Delayed Treatment Initiation among HIV-Positive Patients Living
      in Ontario: A Retrospective Review.
AB  - BACKGROUND: Without a national pharmacare plan in Canada, HIV-infected patients
      across the nation differ in their ability to obtain essential HIV therapy.
      Despite the fact there are public insurance programs in Ontario, patients are
      unable to access medication. The authors described how frequently patients in
      their urban clinic could not access medications and why they required a
      compassionate supply of HIV drugs, with the goals of minimizing treatment delays
      and avoiding interruptions. METHODS: The authors conducted a retrospective review
      and collected information about demographic characteristics, current drug
      insurance and the challenges encountered. RESULTS: Over one year, the authors
      provided 2,886 days of free HIV drugs to 42 patients who were predominantly
      citizens or permanent residents of Canada (88%). The most common obstacles were
      associated with the Trillium Drug Program and the total value of all drugs
      supplied was $134,860. INTERPRETATION: This study suggests that Ontario's
      catastrophic drug insurance plan leaves some patients with significant gaps in
      drug coverage.

PMID- 25947036
TI  - The risk of secondary primary malignancies after therapy for multiple myeloma.
AB  - The development of a secondary primary malignancy (SPM) has become an important
      issue in myeloma management, given the remarkable improvement in survival
      afforded by the introduction of novel agents. Treatment with immunomodulatory
      derivatives, specifically lenalidomide, has recently been identified as a
      potential risk factor for SPM in several studies, especially in the maintenance
      setting. This study reviews potential mechanisms for development of SPM,
      incidence of SPM with different treatment regimens, risk factors associated with
      SPM and features of SPM after myeloma therapy. The incidence of SPM is discussed
      in the context of different settings in which lenalidomide is used during the
      course of the disease. No clear evidence indicates that lenalidomide alone is
      associated with SPM in the absence of other risk factors. Routine cancer
      surveillance, lifestyle modification to avoid cancer risk factors and prompt
      evaluation if new symptoms occur should be emphasized to patients who are on
      continuous myeloma therapy. 

PMID- 25947037
TI  - Change of health-related profiles after Imatinib cessation in chronic phase
      chronic myeloid leukemia patients.
AB  - The aim of this study was to investigate the changes in health-related profiles
      including quality-of-life (HRQoL) in the chronic myeloid leukemia (CML) patients
      who discontinued imatinib (IM). An HRQoL survey composed of 43 parameters about
      IM-related adverse events (AEs), physical health-related and mental health
      related was provided at baseline and 6 months post-discontinuation. A total of 55
      patients with a sustained UMRD over 6 months were analyzed. Although the majority
      of IM-related AEs were significantly improved, unexpectedly pruritus and
      musculoskeletal pain worsen or newly develop in 29.1% and 21.8% of patients,
      respectively. The improvements in physical and mental health condition were
      variable in individual patients. In addition, rapid restorations of the
      hematological and biochemical parameters were observed. The results showed the
      changes of HRQoL and laboratory tests in treatment-off patients and the necessity
      of continuing physical and mental support for some patients in tyrosine kinase
      inhibitor (TKI)-off studies.

PMID- 25947038
TI  - One-Step Fabrication of a Multifunctional Magnetic Nickel Ferrite/Multi-walled
      Carbon Nanotubes Nanohybrid-Modified Electrode for the Determination of Benomyl
      in Food.
AB  - Benomyl, as one kind of agricultural pesticide, has adverse impact on human
      health and the environment. It is urgent to develop effective and rapid methods
      for quantitative determination of benomyl. A simple and sensitive
      electroanalytical method for determination of benomyl using a magnetic nickel
      ferrite (NiFe2O4)/multi-walled carbon nanotubes (MWCNTs) nanohybrid-modified
      glassy carbon electrode (GCE) was presented. The electrocatalytic properties and
      electroanalysis of benomyl on the modified electrode were investigated by cyclic
      voltammetry (CV) and differential pulse voltammetry (DPV). In the phosphate
      buffered saline (PBS) of pH 6.0, this constructed biosensor exhibited two linear
      relationships with the benomyl concentration range from 1.00 * 10(-7) to 5.00 *
      10(-7) mol/L and from 5.00 * 10(-7) to 1.00 * 10(-5) mol/L, respectively. The
      detection limit was 2.51 * 10(-8) mol/L (S/N = 3). Moreover, the proposed method
      was successfully applied to determine benomyl in real samples with satisfactory
      results. The NiFe2O4/MWCNTs/GCE showed good reproducibility and stability,
      excellent catalytic activity, and anti-interference.

PMID- 25947039
TI  - Cognitive complaints in cancer: The French version of the Functional Assessment
      of Cancer Therapy-Cognitive Function (FACT-Cog), normative data from a healthy
      population.
AB  - Cancer patients often report cognitive changes after chemotherapy. The Functional
      Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) is a self-report
      questionnaire that assesses these changes. The aims of the present study were (1)
      to establish normative data, and (2) to compare the scores of patients and
      healthy controls to assess whether or not the questionnaire is able to
      discriminate between these populations. The normative sample included 213 healthy
      participants. The patient group included 63 cancer patients treated with
      chemotherapy, who were compared to a subsample of 63 matched healthy controls.
      The questionnaire had good internal consistency reliability (Cronbach's alphas =
      .74-.91). The oldest patients had significantly more cognitive complaints (p <
      .001). Cognitive complaints were significantly related with Trail Making Test
      scores (p < .001). Furthermore, the FACT-Cog subscales correlated significantly
      with anxiety and depression. Patients had more complaints than matched controls
      on the subscales Perceived Cognitive Impairments (p = .01), Impact on Quality of
      Life (p = .001) and Perceived Cognitive Abilities (p = .027). The reference
      values from the healthy population reported here could be used for comparison
      with the values measured in French-speaking cancer patients. The values provide a
      benchmark against which clinicians can evaluate the impact of the disease and/or
      the treatments on cognitive complaints and help to improve quality of life by
      providing appropriate care. 

PMID- 25947040
TI  - Tuning ligand effects and probing the inner-workings of bond activation steps:
      generation of ruthenium complexes with tailor-made properties.
AB  - Activating chemical bonds through external triggers and understanding the
      underlying mechanism are at the heart of developing molecules with catalytic and
      switchable functions. Thermal, photochemical, and electrochemical bond activation
      pathways are useful for many chemical reactions. In this Article, a series of
      Ru(II) complexes containing a bidentate and a tripodal ligand were synthesized.
      Starting from all-pyridine complex 1(2+), the pyridines were stepwise substituted
      with "click" triazoles (2(2+)-7(2+)). Whereas the thermo- and photoreactivity of
      1(2+) are due to steric repulsion within the equatorial plane of the complex,
      3(2+)-6(2+) are reactive because of triazoles in axial positions, and 4(2+) shows
      unprecedented photoreactivity. Complexes that feature neither steric interactions
      nor axial triazoles (2(2+) and 7(2+)) do not show any reactivity. Furthermore, a
      redox-triggered conversion mechanism was discovered in 1(2+), 3(2+), and 4(2+).
      We show here ligand design principles required to convert a completely inert
      molecule to a reactive one and vice versa, and provide mechanistic insights into
      their functioning. The results presented here will likely have consequences for
      developing a future generation of catalysts, sensors, and molecular switches. 

PMID- 25947041
TI  - Shelf-stable electrophilic reagents for trifluoromethylthiolation.
AB  - Fluorine, which is the most electronegative element and has a small atomic
      radius, plays a key role in pharmaceutical, agrochemical, and materials sciences.
      One of the fluoroalkyl groups, the trifluoromethylthio group (CF3S-), has been
      well-recognized as an important structural motif in the design of lead compounds
      for new drug discovery because of its high lipophilicity (Hansch lipophilicity
      parameter pi = 1.44) and strong electron-withdrawing properties, which could
      improve the drug molecule's cell-membrane permeability and enhance its chemical
      and metabolic stability. While classic methods for the preparation of
      trifluoromethylthiolated compounds typically involve halogen-fluorine exchange
      reactions of polyhalogenomethyl thioethers or trifluoromethylation of sulfur
      containing compounds under harsh reaction conditions, an alternative but more
      attractive strategy is direct trifluoromethylthiolation of the substrate at a
      late stage by employing an electrophilic trifluoromethylthiolating reagent.
      Although several electrophilic trifluoromethylthiolating reagents have been
      reported previously, these reagents either require a strong Lewis acid/Bronsted
      acid as an activator or suffer from a toxic nature or limited substrate scope. To
      address these problems, in late 2011 we initiated a project with the aim to
      develop new, shelf-stable, and highly reactive electrophilic
      trifluoromethylthiolating reagents that could easily install the
      trifluoromethylthio group at the desired positions of the drug molecule at a late
      stage of drug development. Inspired by the broad reactivity of the hypervalent
      iodine reagent, we initially discovered a highly reactive
      trifluoromethylthiolating reagent, trifluoromethanesulfenate 1a. Structure
      reactivity studies disclosed that the iodine atom of reagent 1a does not play an
      important role in this reagent's reactivity. Consequently, a simplified second
      generation electrophilic reagent, trifluoromethanesulfenate 1b, was developed. In
      parallel, we developed another shelf-stable, highly reactive electrophilic
      reagent with a broad substrate scope, N-trifluoromethylthiosaccharin (2). In this
      Account, we mainly describe our discovery of these two different types of
      electrophilic trifluoromethylthiolating reagents, trifluoromethanesulfenates 1a
      and 1b and N-trifluoromethylthiosaccharin 2. Systematic studies showed that both
      types of reagents are highly reactive toward a wide range of nucleophiles, yet
      the substrate scopes of these two different types of reagents are complementary.
      In particular, reagents 1a and 1b are more reliable in transition-metal-catalyzed
      reactions such as copper-catalyzed trifluoromethylthiolation of
      aryl/vinyl/alkylboronic acids and silver-catalyzed decarboxylative
      trifluoromethylthiolation of aliphatic carboxylic acids as well as in the
      organocatalytic asymmetric trifluoromethylthiolation of beta-keto esters and
      oxindoles. Reagent 2 is more electrophilic than reagents 1a and 1b and is more
      efficient for direct trifluoromethylthiolation with nucleophiles such as
      alcohols, amines, thiols, and electron-rich arenes. The ease in preparation,
      broad scope, and mild reaction conditions make reagents 1a, 1b, and 2 very
      attractive as general reagents that allow rapid installation of the
      trifluoromethylthio group into small molecules. 

PMID- 25947042
TI  - Are we entering a new age for human vaccine adjuvants?
AB  - Major advances in adjuvant development for human vaccines have been reported
      recently for a range of indications, including malaria, influenza and varicella
      zoster virus. Furthermore, there is an increased understanding of adjuvant
      mechanisms of action and a greater emphasis on the importance of formulation and
      characterization. This progress may signify a new golden age of vaccine adjuvant
      discovery and development. 

PMID- 25947043
TI  - Therapeutic drug monitoring of anti-TNF-alpha agents in inflammatory bowel
      diseases.
AB  - INTRODUCTION: The elaboration of effective and cost-saving algorithms for anti
      TNF optimization in patients with inflammatory bowel diseases (IBD) represents
      one of the biggest challenges over the last few years. Recently, many studies
      have been focused on the identification of an optimal trough level (TL) for most
      used anti-TNF agents and on the role of anti-drug antibodies (ADAs), especially
      in the management of patients who lose response to biological treatments.
      Therapeutic drug monitoring may potentially help to also prevent lose of clinical
      benefit overtime and to reduce health-related costs. AREAS COVERED: Current
      evidence about the correlation between clinical outcomes and anti-TNF TLs, the
      role of ADAs in the context of safety and loss of response to anti-TNF, the
      utility of therapeutic drug monitoring in clinical practice. EXPERT OPINION: The
      data available so far support the utility of TL and ADA measurement for the
      management of IBD patients with loss of response to anti-TNF but does not
      currently authorizes a routine application in clinical practice of proactive
      therapeutic monitoring in patients in clinical remission. However, this remains a
      promising approach to optimize anti-TNF therapies and possibly to reduce health
      related costs, then further prospective studies are strongly expected.

PMID- 25947044
TI  - Leptospirosis in the Tohoku region: re-emerging infectious disease.
AB  - Leptospirosis is a zoonotic and disaster-related infectious disease. It is mainly
      endemic in subtropical or tropical countries and has not been reported since 2009
      in the Tohoku region (northern Japan), including the Yamagata and Miyagi
      Prefectures. However, we experienced four patients with leptospirosis in the
      Tohoku region from 2012 to 2014; three patients (#1-3) live in the agricultural
      areas of the Yamagata Prefecture and one patient (#4) was a visitor to the Miyagi
      Prefecture. Patient 1 (81-year-old female) is a villager, with a rat bite, while
      Patient 2 (77-year-old male) and Patient 3 (84-year-old female) are farmers and
      were infected probably during agriculture work. Patient 4 (40-year-old male US
      citizen) was infected while traveling in Thailand. They had chief complaint of
      fever, headache, and myalgia and showed manifestations of hyperbilirubinemia
      (mean, 4.35 mg/dL), thrombocytopenia and acute kidney injury (AKI). All patients
      were diagnosed by polymerase chain reaction using blood and/or urine samples and
      a microscopic agglutination test for the anti-Leptospira antibody. All the
      patients were treated with infused antibiotics, including minocycline. The
      patients underwent hemodialysis due to severe AKI (mean serum creatinine, 4.44
      mg/dL), except for Patient 2 with the normal serum creatinine level (1.12 mg/dL).
      All the patients recovered and were discharged. The presence of the three
      patients in the Yamagata Prefecture implies that leptospirosis does re-emerge in
      the Tohoku region. Therefore, careful survey of the pathogen is necessary for
      febrile patients with AKI who engage in agriculture or have a recent history of
      travelling in subtropical or tropical countries. 

PMID- 25947045
TI  - Multicolor FISHs for simultaneous detection of genes and DNA segments on human
      chromosomes.
AB  - We have developed a convenient multicolor fluorescent in situ hybridization
      (FISH) (five-, four-, three-, and two-color FISHs) for detecting specific
      genes/DNA segments on the human chromosomes. As a foundation of multicolor FISH,
      we first isolated 80 bacterial artificial chromosome (BAC) probes that
      specifically detect the peri-centromeres (peri-CEN) and subtelomeres (subTEL) of
      24 different human chromosomes (nos. 1~22, X, and Y) by screening our homemade
      BAC library (Keio BAC library) consisting of 200,000 clones. Five-color FISH was
      performed using human DNA segments specific for peri-CEN or subTEL, which were
      labeled with five different fluorescent dyes [7-diethylaminocoumarin (DEAC):
      blue, fluorescein isothiocyanate (FITC): green, rhodamine 6G (R6G): yellow,
      TexRed: red, and cyanine5 (Cy5): purple]. To observe FISH signals under a
      fluorescence microscope, five optic filters were carefully chosen to avoid
      overlapping fluorescence emission. Five-color FISH and four-color FISH enabled us
      to accurately examine the numerical anomaly of human chromosomes. Three-color
      FISH using two specific BAC clones, that distinguish 5' half of oncogene
      epidermal growth factor receptor (EGFR) from its 3' half, revealed the
      amplification and truncation of EGFR in EGFR-overproducing cancer cells.
      Moreover, two-color FISH readily detected a fusion gene in leukemia cells such as
      breakpoint cluster region (BCR)/Abelson murine leukemia viral oncogene homologue
      (ABL) on the Philadelphia (Ph') chromosome with interchromosomal translocation.
      Some other successful cases such as trisomy 21 of Down syndrome are presented.
      Potential applications of multicolor FISH will be discussed. 

PMID- 25947046
TI  - Formation and thermodynamics of gaseous germanium and tin vanadates: a mass
      spectrometric and quantum chemical study.
AB  - The stabilities of gaseous germanium and tin vanadates were confirmed by high
      temperature mass spectrometry, and its structures were determined by quantum
      chemical calculations. A number of gas-phase reactions involving these gaseous
      salts were studied. On the basis of the equilibrium constants, the standard
      formation enthalpies of gaseous GeV2O6 (-1520 +/- 42 kJ mol(-1)) and SnV2O6 (
      1520 +/- 43 kJ mol(-1)) were determined at a temperature of 298 K. 

PMID- 25947047
TI  - Real-time emissions from construction equipment compared with model predictions.
AB  - The construction industry is a large source of greenhouse gases and other air
      pollutants. Measuring and monitoring real-time emissions will provide
      practitioners with information to assess environmental impacts and improve the
      sustainability of construction. We employed a portable emission measurement
      system (PEMS) for real-time measurement of carbon dioxide (CO), nitrogen oxides
      (NOx), hydrocarbon, and carbon monoxide (CO) emissions from construction
      equipment to derive emission rates (mass of pollutant emitted per unit time) and
      emission factors (mass of pollutant emitted per unit volume of fuel consumed)
      under real-world operating conditions. Measurements were compared with emissions
      predicted by methodologies used in three models: NONROAD2008, OFFROAD2011, and a
      modal statistical model. Measured emission rates agreed with model predictions
      for some pieces of equipment but were up to 100 times lower for others. Much of
      the difference was driven by lower fuel consumption rates than predicted.
      Emission factors during idling and hauling were significantly different from each
      other and from those of other moving activities, such as digging and dumping. It
      appears that operating conditions introduce considerable variability in emission
      factors. Results of this research will aid researchers and practitioners in
      improving current emission estimation techniques, frameworks, and databases.

PMID- 25947048
TI  - Leaching kinetics of bottom ash waste as a source of calcium ions.
AB  - Bottom ash is a waste material from coal-fired power plants, and it is known to
      contain elements that are potentially toxic at high concentration levels when
      disposed in landfills. This study investigates the use of bottom ash as a partial
      substitute sorbent for wet flue gas desulfurization (FGD) processes by focusing
      on its leaching kinetics in adipic acid. This was studied basing on the shrinking
      core model that was applied to the experimental data obtained by the authors
      presented at the International Conference on Industrial, Manufacturing,
      Automation and Mechanical Engineering, Johannesburg, South Africa, November 27
      28, 2013) on dissolution of bottom ash. The leaching rate constant was obtained
      from different reaction variables, namely, temperature, pH, acid concentration,
      and solid-to-liquid ratio, that could affect the leaching process. The solid
      sample of bottom ash was characterized at different leaching periods using X-ray
      diffraction (XRD) and scanning electron microscopy (SEM). It was found that solid
      to-liquid ratio had a significant effect on the leaching rate constant when
      compared with other variables. The leaching kinetics showed that diffusion
      through the product layer was the rate-controlling step during leaching, and the
      activation energy for the process was found to be 18.92 kJ/mol.

PMID- 25947049
TI  - Biofiltration of gasoline and diesel aliphatic hydrocarbons.
AB  - The ability of a biofilm to switch between the mixtures of mostly aromatic and
      aliphatic hydrocarbons was investigated to assess biofiltration efficiency and
      potential substrate interactions. A switch from gasoline, which consisted of both
      aliphatic and aromatic hydrocarbons, to a mixture of volatile diesel n-alkanes
      resulted in a significant increase in biofiltration efficiency, despite the lack
      of readily biodegradable aromatic hydrocarbons in the diesel mixture. This
      improved biofilter performance was shown to be the result of the presence of
      larger size (C9-C(12)) linear alkanes in diesel, which turned out to be more
      degradable than their shorter-chain (C6-C8) homologues in gasoline. The evidence
      obtained from both biofiltration-based and independent microbiological tests
      indicated that the rate was limited by biochemical reactions, with the inhibition
      of shorter chain alkane biodegradation by their larger size homologues as
      corroborated by a significant substrate specialization along the biofilter bed.
      These observations were explained by the lack of specific enzymes designed for
      the oxidation of short-chain alkanes as opposed to their longer carbon chain
      homologues.

PMID- 25947050
TI  - Capture of methyl bromide emissions with activated carbon following the
      fumigation of a small building contaminated with a Bacillus anthracis spore
      simulant.
AB  - A wide-area Bacillus anthracis spore contamination incident will present immense
      challenges related to decontamination capacity. For this reason, fumigation with
      methyl bromide (MeBr) has been proposed as a potential remediation option.
      Although a few bench-scale laboratory studies have been conducted to evaluate
      activated carbon for the capture of MeBr, these studies were conducted at
      conditions replicating commodity fumigation using relatively low MeBr
      concentrations, temperatures, and/or relative humidity (RH) levels. The more
      rigorous MeBr fumigation requirements to fully inactivate B. anthracis spores are
      much more of a challenge for an activated carbon system (ACS) to capture MeBr,
      and warrant their own investigation. Further, while the aforementioned studies
      have shown activated carbon to be a possible option for the capture of MeBr in
      gas streams, these tests were conducted at laboratory bench scale, and thus lack
      operational perspective and data. Thus, we present for the first time the results
      of a full-scale study to evaluate an ACS employed for the capture of MeBr at
      conditions that would be used for decontaminating a building structure
      contaminated with B. anthracis spores. Airflow rate, temperature, RH, and MeBr
      levels were measured within the ACS during its operation. Despite the relatively
      high humidity, temperature, and MeBr levels, the MeBr capture efficiency of the
      ACS was demonstrated to be more than 99%. The concentration of MeBr exhausted
      from the structure was reduced from 41,000 to 136 ppmv in 3.5 hr, corresponding
      to an overall atmospheric emission rate of less than 2 kg. The practical
      adsorption rate of the ACS was determined to be 4.83 kg MeBr/100 kg carbon. The
      information and data presented here will facilitate future use of this technology
      when fumigating with MeBr.

PMID- 25947051
TI  - A variance decomposition approach to uncertainty quantification and sensitivity
      analysis of the Johnson and Ettinger model.
AB  - The Johnson and Ettinger (J&E) model is the most widely used vapor intrusion
      model in the United States. It is routinely used as part of hazardous waste site
      assessments to evaluate the potential for vapor intrusion exposure risks. This
      study incorporates mathematical approaches that allow sensitivity and uncertainty
      of the J&E model to be evaluated. In addition to performing Monte Carlo
      simulations to examine the uncertainty in the J&E model output, a powerful global
      sensitivity analysis technique based on Sobol indices is used to evaluate J&E
      model sensitivity to variations in the input parameters. The results suggest that
      the J&E model is most sensitive to the building air exchange rate, regardless of
      soil type and source depth. Building air exchange rate is not routinely measured
      during vapor intrusion investigations, but clearly improved estimates and/or
      measurements of the air exchange rate would lead to improved model predictions.
      It is also found that the J&E model is more sensitive to effective diffusivity
      than to effective permeability. Field measurements of effective diffusivity are
      not commonly collected during vapor intrusion investigations; however,
      consideration of this parameter warrants additional attention. Finally, the
      effects of input uncertainties on model predictions for different scenarios
      (e.g., sandy soil as compared to clayey soil, and "shallow" sources as compared
      to "deep" sources) are evaluated. Our results not only identify the range of
      variability to be expected depending on the scenario at hand, but also mark the
      important cases where special care is needed when estimating the input parameters
      to which the J&E model is most sensitive.

PMID- 25947052
TI  - Adsorption and oxidation of SO2in a fixed-bed reactor using activated carbon
      produced from oxytetracycline bacterial residue and impregnated with copper.
AB  - The SO2removal ability (including adsorption and oxidation ability) of activated
      carbon produced from oxytetracycline bacterial residue and impregnated with
      copper was investigated. The activated carbon produced from oxytetracycline
      bacterial residue and modified with copper was characterized by x-ray
      diffraction, scanning electron microscopy, and energy-dispersive spectroscopy.
      The effects of the catalysts, SO2concentration, weight hourly space velocity, and
      temperature on the SO2adsorption and oxidation activity were evaluated. Activated
      carbon produced from oxytetracycline bacterial residue and used as catalyst
      supports for copper oxide catalysts provided high catalytic activity for the
      adsorbing and oxidizing of SO2from flue gases.

PMID- 25947053
TI  - Dispersion modeling of particulate matter containing hexavalent chromium during
      high winds in southern Iraq.
AB  - The aim of this paper is to describe a scientific methodology (i.e., the
      combination of different well-established modeling techniques) and its
      application to a real case scenario of contaminated dust emissions in high winds.
      This scenario addresses potential air pollution problems at the water treatment
      plant (WTP) at Qarmat-Ali, Basra, Iraq, during 2003. Workplace practices at the
      WTP before 2003 resulted in sodium dichromate contamination in the area. Looting
      at the site in early 2003 also contributed to this contamination. Individuals who
      were assigned to provide security at the site in 2003 have claimed adverse health
      effects caused by exposure to dust containing hexavalent chromium [Cr(VI)]. This
      report presents our modeling study with respect to these claims in relation to
      (1) amount of Cr(VI) present in the soil, (2) wind erosion episodes, and (3)
      possible long-term (e.g., annual average) Cr(VI) concentrations inhaled by
      different people while at the site. Our modeling approach included (1) the
      analysis of Cr(VI) soil measurements to assess the degree of contamination in
      different areas of the plant at different times; (2) the use of DUSTRAN model
      equations to calculate the emission rate of particulate matter (PM) less than 10
      um in diameter (PM10) during high-wind episodes; (3) the use of the U.S.
      Environmental Protection Agency (EPA) AERMOD modeling system to estimate Cr(VI)
      concentrations at the site; and (4) the calculation of modeling results in the
      form of both contour lines of average Cr(VI) concentrations at the site, and
      specific concentration values for selected individuals, based upon their
      recollection of their visits to the site.

PMID- 25947054
TI  - Air emission from the co-combustion of alternative derived fuels within cement
      plants: Gaseous pollutants.
AB  - Cement manufacturing is a resource- and energy-intensive industry, utilizing 9%
      of global industrial energy use while releasing more than 5% of global carbon
      dioxide (CO2) emissions. With an increasing demand of production set to double by
      2050, so too will be its carbon footprint. However, Australian cement plants have
      great potential for energy savings and emission reductions through the
      substitution of combustion fuels with a proportion of alternative derived fuels
      (ADFs), namely, fuels derived from wastes. This paper presents the environmental
      emissions monitoring of 10 cement batching plants while under baseline and ADF
      operating conditions, and an assessment of parameters influencing combustion. The
      experiential runs included the varied substitution rates of seven waste streams
      and the monitoring of seven target pollutants. The co-combustion tests of waste
      oil, wood chips, wood chips and plastic, waste solvents, and shredded tires were
      shown to have the minimal influence when compared to baseline runs, or had
      significantly reduced the unit mass emission factor of pollutants. With an
      increasing ADF% substitution, monitoring identified there to be no subsequent
      emission effects and that key process parameters contributing to contaminant
      suppression include (1) precalciner and kiln fuel firing rate and residence time;
      (2) preheater and precalciner gas and material temperature; (3) rotary kiln flame
      temperature; (4) fuel-air ratio and percentage of excess oxygen; and (5) the rate
      of meal feed and rate of clinker produced.

PMID- 25947055
TI  - Mapping out the solid waste generation and collection models: The case of Kampala
      City.
AB  - This paper presents a mapping of the waste collection systems in Kampala city,
      using geographical information system (GIS) ArcGIS mapping software. It discusses
      the existing models of waste collection to the final disposal destinations. It
      was found that food and yard wastes constitute 92.7% of the waste generated in
      Kampala. Recyclables and other special wastes constitute only 7.3% of the total
      waste, mainly because of the increased level of reuse and recycling activities.
      The generation rate of solid wastes was on average, 582, 169, 105, and 90
      tons/day from poor areas, upscale wealthier areas, business centers, and market
      areas respectively. This tonnage of waste was collected, transported, and
      disposed of at the city landfill. The study found that in total, residential
      areas of poor people generate more waste than other categories stated earlier,
      mainly because of their large populations. In total, there were 133 unofficial
      temporary storage sites acknowledged by Kampala Capital City Authority (KCCA) but
      not formally designated, 59 illegal dump sites, and 35 officially recognized
      temporary waste storage locations. This paper presents large-scale data that can
      help with understanding the collection models and their influence on solid waste
      management in Kampala city, which could be used for similar cities in developing
      countries.

PMID- 25947056
TI  - Modeling of particulate matter dispersion from a poultry facility using AERMOD.
AB  - This study evaluates the performance of AERMOD, the current U.S. Environmental
      Protection Agency (EPA) regulatory model, in simulating particulate matter (PM10
      and PM2.5) dispersion from a poultry pullet facility. At the source, the daily
      mean PM10 and PM2.5 concentrations with strong diurnal patterns were estimated to
      be 436.01 +/- 166.77 MUg m-3 and 291.09 +/- 105.81 MUg m-3, respectively. This
      corresponded to daily mean emission rates of PM10 and PM2.5 as 0.067-0.073 g sec
      1 and 0.044-0.047 g sec-1,respectively. The modeled hourly PM concentration
      showed acceptable accuracy relative to the measured PM concentrations downwind of
      the source. Increasing the averaging period from hourly to daily resulted in
      improved prediction. The simulations revealed that PM concentrations at and
      beyond the property line of the poultry facility were within the National Ambient
      Air Quality Standards. This study suggested that AERMOD is effective in
      predicting and assessing the impacts of PM downwind of poultry facilities.

PMID- 25947057
TI  - An investigation of potential regional and local source regions affecting fine
      particulate matter concentrations in Delhi, India.
AB  - In this study, potential regional and local sources influencing PM2.5
      (particulate matter with an aerodynamic diameter >2.5 MUm) concentrations in
      Delhi, India, are identified and their possible impact evaluated through diverse
      approaches based on study of variability of synoptic and local airflow patterns
      that transport aerosol concentrations from these emission sources to an urban
      receptor site in Delhi, India. Trajectory clustering of 72-hr and 48-hr back
      trajectories simulated at arrival heights of 500 m and 100 m, respectively, every
      hour for representative years 2008-2010 are used to assess the relative influence
      of long-distance, regional, and subregional sources on this site. Nonparametric
      statistical procedures are employed on trajectory clusters to better delineate
      various distinct regional pollutant source regions. Trajectory clustering and
      concentration-weighted trajectory (CWT) analyses indicate that regional and
      subregional PM2.5 emission sources in neighboring country of Pakistan and
      adjacent states of Punjab, Haryana, and Uttar Pradesh contribute significantly to
      the total surplus of aerosol concentrations in the Delhi region. Conditional
      probability function and Bayesian approach used to identify local source regions
      have established substantial influence from highly urbanized satellite towns
      located southwest (above 25%) and southeast (above 45%) of receptor location.
      There is significant seasonal variability in synoptic and local air circulation
      patterns, which is discerned in variability in seasonal concentrations. Mean of
      daily averaged PM2.5 concentrations at the Income Tax Office (ITO) receptor site
      over Delhi at 95% confidence level is highest in winter, ranging between 209 and
      185 MUg m-3 for the entire study period. The annual variability in air transport
      pathways is more in winter than in other seasons. Year-to-year variability is
      present in aerosol concentrations, especially during winter, with standard
      deviations varying from a minimum of 60 ug m-3 in winter 2009 to a maximum of 109
      ug m-3 in winter 2010.

PMID- 25947058
TI  - A spatial multicriteria model for determining air pollution at sample locations.
AB  - Atmospheric pollution in urban centers has been one of the main causes of human
      illness related to the respiratory and circulatory system. Efficient monitoring
      of air quality is a source of information for environmental management and public
      health. This study investigates the spatial patterns of atmospheric pollution
      using a spatial multicriteria model that helps target locations for air pollution
      monitoring sites. The main objective was to identify high-priority areas for
      measuring human exposures to air pollutants as they relate to emission sources.
      The method proved to be viable and flexible in its application to various areas.

PMID- 25947059
TI  - Emerging Role of the Hippo Signaling Pathway in Position Sensing and Lineage
      Specification in Mammalian Preimplantation Embryos.
AB  - In preimplantation mouse embryos, the first lineage differentiation takes place
      in the 8- to 16-cell-stage embryo and results in formation of the trophectoderm
      (TE) and inner cell mass (ICM), which will give rise to the trophoblast of the
      placenta and the embryo proper, respectively. Although, it is widely accepted
      that positioning of a cell within the embryo influences lineage differentiation,
      the mechanism underlying differential lineage differentiation and how it involves
      cell position are largely unknown. Interestingly, novel cues from the Hippo
      pathway have been recently demonstrated in the preimplantation mouse embryo.
      Unlike the mechanisms reported from epithelium-cultured cells, the Hippo pathway
      was found to be responsible for translating positional information to lineage
      specification through a position-sensing mechanism. Disruption of Hippo pathway
      component genes in early embryos results in failure of lineage specification and
      failure of postimplantation development. In this review, we discuss the unique
      role of the Hippo signaling pathway in early embryo development and its role in
      lineage specification. Understanding the activity and regulation of the Hippo
      pathway may offer new insights into other areas of developmental biology that
      evolve from understanding of this cell-fate specification in the early embryonic
      cell. 

PMID- 25947060
TI  - ROS-Generating Oxidase Nox3 Regulates the Self-Renewal of Mouse Spermatogonial
      Stem Cells.
AB  - Spermatogonial stem cells (SSCs) represent a unique population of germ cells with
      self-renewal potential. Although reactive oxygen species (ROS) are considered
      toxic to germ cells, we recently showed that moderate levels of ROS are required
      for SSC self-renewal and that Nox1 is involved in ROS generation. In this study,
      we showed that self-renewal factor treatment induces Nox3 to trigger SSC self
      renewal. Nox3 was transiently expressed in cultured spermatogonia by FGF2 and
      GDNF stimulation, whereas Nox1 was expressed predominantly during the stable
      phase of proliferation. Nox3 inhibition by short hairpin RNA reduced cytokine
      induced ROS generation and limited the proliferation of cultured spermatogonia.
      Although Nox3 overexpression revealed no apparent effect, depletion of Nox3
      decreased the number of SSCs in both cultured spermatogonia and freshly isolated
      testis cells. Our results suggest that self-renewal of SSCs is regulated by
      sequential activation of different Nox genes, and underscore the complexity of
      ROS regulation in the self-renewal division of SSCs. 

PMID- 25947061
TI  - 'Conceptualizing' the Endometrium: Identification of Conceptus-Derived Proteins
      During Early Pregnancy in Cattle.
AB  - The aim of this study was to identify conceptus-derived proteins, in addition to
      IFNT, that may facilitate pregnancy recognition in cattle. Analysis of the
      protein content of the uterine luminal fluid (ULF) from cyclic heifers on Day 16
      by nano liquid chromatography tandem mass spectrometry identified 334 proteins.
      Comparison of these data with 299 proteins identified in the ULF of pregnant
      heifers on Day 16 identified 85 proteins only present in the ULF of pregnant
      heifers. Analysis of Day 16 conceptus-conditioned culture medium revealed the
      presence of 1005 proteins of which 30 proteins were unique to ULF from Day 16
      pregnant heifers. Of these 30 proteins, 12 had mRNA expression values at least 2
      fold higher in abundance (P < 0.05) in the conceptus compared to the endometrium
      (ARPC5L, CAPG, CKMT1, CSTB, HSPA8, HSPE1, LGALS3, MSN, NUTF2, P4HB, PRKAR2A, TKT)
      as determined by RNA sequencing. In addition, genes that have a significant
      biological interaction with the proteins (ACO2, CKMT1, CSTB, EEF2, GDI1, GLB1,
      GPLD1, HNRNPA1, HNRNPA2B1, HNRNPF, HSPA8, HSPE1, IDH2, KRT75, LGALS3, MSN, NUTF2,
      P4HB, PRKAR2A, PSMA4, PSMB5, PSMC4, SERPINA3, TKT) were differentially expressed
      in the endometrium of pregnant compared to cyclic heifers during the pregnancy
      recognition period (Days 16-18). These results indicate that 30 proteins unique
      to ULF from pregnant heifers and produced by short-term in vitro cultured Day 16
      conceptuses could potentially be involved in facilitating the interactions
      between the conceptus and the endometrium during the pregnancy recognition
      period. 

PMID- 25947062
TI  - Cross talk between serine/threonine and tyrosine kinases regulates ADP-induced
      thromboxane generation in platelets.
AB  - ADP-induced thromboxane generation depends on Src family kinases (SFKs) and is
      enhanced with pan-protein kinase C (PKC) inhibitors, but it is not clear how
      these two events are linked. The aim of the current study is to investigate the
      role of Y311 phosphorylated PKCdelta in regulating ADP-induced platelet
      activation. In the current study, we employed various inhibitors and murine
      platelets from mice deficient in specific molecules to evaluate the role of
      PKCdelta in ADP-induced platelet responses. We show that, upon stimulation of
      platelets with 2MeSADP, Y311 on PKCdelta is phosphorylated in a P2Y1/Gq and Lyn
      dependent manner. By using PKCdelta and Lyn knockout murine platelets, we also
      show that tyrosine phosphorylated PKCdelta plays a functional role in mediating
      2MeSADP-induced thromboxane generation. 2MeSADP-induced PKCdelta Y311
      phosphorylation and thromboxane generation were potentiated in human platelets
      pre-treated with either a pan-PKC inhibitor, GF109203X or a PKC alpha/beta
      inhibitor and in PKC alpha or beta knockout murine platelets compared to
      controls. Furthermore, we show that PKC alpha/beta inhibition potentiates the
      activity of SFK, which further hyper-phosphorylates PKCdelta and potentiates
      thromboxane generation. These results show for the first time that tyrosine
      phosphorylated PKCdelta regulates ADP-induced thromboxane generation independent
      of its catalytic activity and that classical PKC isoforms alpha/beta regulate the
      tyrosine phosphorylation on PKCdelta and subsequent thromboxane generation
      through tyrosine kinase, Lyn, in platelets. 

PMID- 25947064
TI  - Molecular weight effects on the phase-change-enhanced temperature coefficient of
      resistance in carbon nanotube/poly(N-isopropylacrylamide) composites.
AB  - We investigate the temperature coefficient of resistance (TCR), of carbon
      nanotube composites with the phase-change polymer poly(N-isopropylacrylamide).
      Our results shed light on the underlying mechanism of electron transport through
      networks of conductive paths in the composites and its dependence on the
      molecular weights (MWs) of the phase-changing polymer. Measurements of the
      humidity dependence of the TCR reveal the dominant conduction mechanism to be
      variable range hopping with an exponent of 1/4, corresponding to transport in a
      3D system. In a humid atmosphere, a twenty-fold change in the hopping activation
      energy is observed as the temperature is swept across the polymer's hydrophilic
      to-hydrophobic phase-transition, while no change is observed in low humidity
      atmospheres or in vacuum. The TCR was found to depend on MW but to also be
      affected by details of the dynamics of hydration/dehydration of the composites.
      For operation in dry atmospheres and in vacuum the maximum TCR observed was only
      .002%, while in a humid atmosphere the TCR as large as 60% were observed-an order
      of magnitude higher than those found in common high-TCR materials used in thermal
      sensing applications. 

PMID- 25947063
TI  - Determining minimum set of driver nodes in protein-protein interaction networks.
AB  - BACKGROUND: Recently, several studies have drawn attention to the determination
      of a minimum set of driver proteins that are important for the control of the
      underlying protein-protein interaction (PPI) networks. In general, the minimum
      dominating set (MDS) model is widely adopted. However, because the MDS model does
      not generate a unique MDS configuration, multiple different MDSs would be
      generated when using different optimization algorithms. Therefore, among these
      MDSs, it is difficult to find out the one that represents the true driver set of
      proteins. RESULTS: To address this problem, we develop a centrality-corrected
      minimum dominating set (CC-MDS) model which includes heterogeneity in degree and
      betweenness centralities of proteins. Both the MDS model and the CC-MDS model are
      applied on three human PPI networks. Unlike the MDS model, the CC-MDS model
      generates almost the same sets of driver proteins when we implement it using
      different optimization algorithms. The CC-MDS model targets more high-degree and
      high-betweenness proteins than the uncorrected counterpart. The more central
      position allows CC-MDS proteins to be more important in maintaining the overall
      network connectivity than MDS proteins. To indicate the functional significance,
      we find that CC-MDS proteins are involved in, on average, more protein complexes
      and GO annotations than MDS proteins. We also find that more essential genes,
      aging genes, disease-associated genes and virus-targeted genes appear in CC-MDS
      proteins than in MDS proteins. As for the involvement in regulatory functions,
      the sets of CC-MDS proteins show much stronger enrichment of transcription
      factors and protein kinases. The results about topological and functional
      significance demonstrate that the CC-MDS model can capture more driver proteins
      than the MDS model. CONCLUSIONS: Based on the results obtained, the CC-MDS model
      presents to be a powerful tool for the determination of driver proteins that can
      control the underlying PPI networks. The software described in this paper and the
      datasets used are available at https://github.com/Zhangxf-ccnu/CC-MDS .

PMID- 25947065
TI  - The hazards of approximations and extrapolations: Insights from the ATLANTIC
      study.

PMID- 25947066
TI  - Fatty acid synthase overexpression: target for therapy and reversal of
      chemoresistance in ovarian cancer.
AB  - BACKGROUND: Fatty acid synthase (FASN) is crucial to de novo long-chain fatty
      acid synthesis, needed to meet cancer cells' increased demands for membrane,
      energy, and protein production. METHODS: We investigated FASN overexpression as a
      therapeutic and chemosensitization target in ovarian cancer tissue, cell lines,
      and primary cell cultures. FASN expression at mRNA and protein levels was
      determined by quantitative real-time polymerase chain reaction and immunoblotting
      and immunohistochemistry, respectively. FASN inhibition's impact on cell
      viability, apoptosis, and fatty acid metabolism was assessed by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide assay, cell death detection
      enzyme-linked immunosorbent assay, immunoblotting, and (18) F-fluoromethylcholine
      uptake measurement, respectively. RESULTS: Relative to that in healthy fallopian
      tube tissue, tumor tissues had 1.8-fold average FASN protein overexpression; cell
      lines and primary cultures had 11-fold-100-fold mRNA and protein overexpression.
      In most samples, the FASN inhibitor cerulenin markedly decreased FASN expression
      and cell viability and induced apoptosis. Unlike concomitant administration,
      sequential cerulenin/cisplatin treatment reduced cisplatin's half maximal
      inhibitory concentration profoundly (up to 54%) in a cisplatin-resistant cell
      line, suggesting platinum (re)sensitization. Cisplatin-resistant cells displayed
      lower (18) F-fluoro-methylcholine uptake than did cisplatin-sensitive cells,
      suggesting that metabolic imaging might help guide therapy. CONCLUSIONS: FASN
      inhibition induced apoptosis in chemosensitive and platinum-resistant ovarian
      cancer cells and may reverse cisplatin resistance.

PMID- 25947067
TI  - Primary extranodal marginal zone B-cell lymphoma with diffuse uveal involvement
      and focal infiltration of the trabecular meshwork: a case report and review of
      literature.
AB  - BACKGROUND: Primary extranodal marginal zone lymphoma (EMZL) of the uvea is a
      rare condition and diagnosis may be challenging. We aim to report the clinical,
      histopathologic and immunohistochemical findings in a case of primary EMZL with
      diffuse uveal involvement and focal infiltration of the trabecular meshwork. CASE
      PRESENTATION: A 38-year-old male presented with 2-year progressive vision loss in
      the right eye. Fundus examination showed choroidal thickening with diffuse
      retinal pigment epithelium (RPE) changes and inferior exudative retinal
      detachment. Ultrasonography revealed low-reflective masses with diffuse
      thickening of the choroid involving the optic nerve and orbit. Despite treatment
      with steroids, his symptoms progressed over time. One year later, visual acuity
      of the right eye markedly decreased to no light perception and enucleation was
      performed. Histopathological findings revealed infiltrates of malignant cells in
      the choroid, iris, ciliary body and trabecular meshwork. Immunohistochemistry
      confirmed the diagnosis of primary uveal EMZL. CONCLUSIONS: This is the first
      case reporting primary EMZL diffusely involving the uvea with focal infiltration
      of the trabecular meshwork.

PMID- 25947068
TI  - Stable and color tunable emission properties based on non-cyclometalated
      gold(III) complexes.
AB  - Stable and emission tunable non-cyclometalated gold(III) triaryl complexes of the
      type [(L)Au(C6F5)3] [L = 2-(2,4-difluorophenylpyridine) (1), 4-phenylpyridine
      (2), 2-phenylpyridine (3), 2-phenylisoquinoline (4), 2-thienylpyridine (5)] were
      synthesized starting from a common precursor complex [(THT)Au(C6F5)3] [THT =
      tetrahydrothiophene] in good to modest yields. Extensive characterization of the
      complexes by various nuclear magnetic resonance spectroscopy techniques and
      elemental analysis further corroborated the single-crystal X-ray diffraction
      studies. The complexes displayed room temperature phosphorescence in the neat
      solid and in 2-MeTHF at 77 K. Detailed photophysical investigations of the
      complexes in the neat solid and at 77 K revealed the successful tuning of the
      emission maxima with modest quantum yields across the visible part of the
      electromagnetic spectrum depending on the electronic properties of the
      heterocyclic ligands. DFT (Density Functional Theory) and TDDFT (Time Dependent
      Density Functional Theory) calculations were performed to discern the composition
      of the excited state as well as confirm the obtained relative emission energies
      upon substitution with electronically different ligands. The obtained diverse
      emissive behavior of the complexes combined with the ease of synthesis illustrate
      the generality and applicability of the design approach to obtain emissive
      gold(iii) complexes devoid of cyclometalation.

PMID- 25947069
TI  - Open debridement and prosthesis retention is a viable treatment option for acute
      periprosthetic joint infection after total knee arthroplasty.
AB  - PURPOSE: Open debridement with prosthesis retention (ODPR) has been considered as
      a reasonable treatment option for acute periprosthetic joint infection (PJI)
      following total knee arthroplasty (TKA). However, multiple recent studies have
      challenged this contention. This study was undertaken to determine the success
      rate of ODPR, whether the success rate was affected by the ODPR timing or by the
      microorganisms. METHOD: We retrospectively reviewed 52 cases of ODPR performed in
      four institutions to treat acute PJI which met the definition of PJI by the
      International Consensus Group on PJI. We recorded patient demographics; time from
      index TKA and symptom duration; the microorganisms involved; and whether the
      infection was controlled or not. RESULTS: The overall success rate of ODPR was 71
      %, and early postoperative infection and acute hematogenous infection had a
      success rate of 82 and 55 %, respectively. Success rate was associated with a
      shorter symptom duration in patients with acute hematogenous infections (p =
      0.040). However, success was not influenced by the type (p = 0.992) or virulence
      of the causative microorganisms (p = 0.706). CONCLUSION: ODPR should be
      considered as a viable treatment option for acute PJI following TKA. The
      promptness of ODPR is of paramount importance for success of ODPR, rather than
      the causative organism type or virulence.

PMID- 25947070
TI  - Graphene-based single fiber supercapacitor with a coaxial structure.
AB  - A novel all graphene coaxial fiber supercapacitor (GCS) was fabricated,
      consisting of a continuously wet-spun core graphene fiber and facilely dip-coated
      graphene sheath. GCS is flexible, lightweight and strong, and is also accompanied
      by a high specific capacitance of 205 mF cm(-2) (182 F g(-1)) and high energy
      density of 17.5 MUW h cm(-2) (15.5 W h kg(-1)). The energy density was further
      improved to 104 MUW h cm(-2), when an organic ion liquid electrolyte was used. 

PMID- 25947072
TI  - Early Childhood Reticent and Solitary-Passive Behaviors and Adjustment Outcomes
      in Chinese Children.
AB  - Little is known about the developmental outcomes of children's social withdrawal
      in non-Western societies. The present study examined how two main forms of social
      withdrawal, social reticence and solitary-passive behavior, in early childhood
      were associated with adjustment in late childhood in Chinese children (75 boys
      and 92 girls). Data on reticent and solitary-passive behaviors were collected at
      4 years of age from laboratory observations. Follow-up data on school,
      behavioral, and psychological adjustment were collected at 11 years of age from
      multiple sources. It was found that whereas reticent behavior mainly predicted
      later psychological problems such as loneliness and depression, solitary-passive
      behavior predicted later school incompetence and externalizing problems. The
      results suggest that reticence and solitary-passive behavior may represent
      distinct forms of withdrawal that play different roles in maladaptive development
      in Chinese context.

PMID- 25947071
TI  - Multi-Level Models of Internalizing Disorders and Translational Developmental
      Science: Seeking Etiological Insights that can Inform Early Intervention
      Strategies.
AB  - This commentary discusses the articles in this special section with an emphasis
      on the specific utility of multivariate, multi-level models in developmental
      psychopathology for ultimately contributing to both etiologic insights and
      translational advances. These issues are considered not only in terms of the
      specific papers, but also within a larger set of questions regarding the
      opportunities (and challenges) currently facing the field. We describe why we
      believe this an exciting time for integrative team-science approaches to tackle
      these challenges--a time that holds great promise for rapid advances in
      integrative developmental science that includes a biological level of mechanistic
      understanding. In order to facilitate this, we outline a range of approaches
      within both translational neuroscience and translational developmental science
      that can be used as frameworks for understanding how such research can provide
      etiologic insights regarding real-world targets at the level of social,
      behavioral, and affective processes that can be modified during key developmental
      windows of opportunity. We conclude that a "construct validity" framework, where
      biological data form a critical, but not privileged, component of key etiological
      mechanisms, combined with a developmental perspective on key period of
      sensitivity to intervention effects, is most likely to provide significant
      translational outcomes.

PMID- 25947073
TI  - Impacts of electrode potentials and solvents on the electroreduction of CO2: a
      comparison of theoretical approaches.
AB  - Since CO2 is a readily available feedstock throughout the world, the utilization
      of CO2 as a C1 building block for the synthesis of valuable chemicals is a highly
      attractive concept. However, due to its very nature of energy depleted "carbon
      sink", CO2 has a very low reactivity. Electrocatalysis offers the most attractive
      means to activate CO2 through reduction: the electron is the "cleanest" reducing
      agent whose energy can be tuned to the thermodynamic optimum. Under protic
      conditions, the reduction of CO2 over many metal electrodes results in formic
      acid. Thus, to open the road to its utilization as a C1 building block, the
      presence of water should be avoided to allow a more diverse chemistry, in
      particular for C-C bond formation with alkenes. Under those conditions, the
      intrinsic reactivity of CO2 can generate carbonates and oxalates by C-O and C-C
      bond formation, respectively. On Ni(111), almost exclusively carbonates and
      carbon monoxide are evidenced experimentally. Despite recent progress in
      modelling electrocatalytic reactions, determining the actual mechanism and
      selectivities between competing reaction pathways is still not straight forward.
      As a simple but important example of the intrinsic reactivity of CO2 under
      aprotic conditions, we highlight the shortcomings of the popular linear free
      energy relationship for electrode potentials (LFER-EP). Going beyond this zeroth
      order approximation by charging the surface and thus explicitly including the
      electrochemical potential into the electronic structure computations allows us to
      access more detailed insights, shedding light on coverage effects and on the
      influence of counterions. 

PMID- 25947074
TI  - Keggin-type polyoxometalate-based ionic liquid gels.
AB  - A series of reversible phase transformation ammonium- and phosphonium-based
      polyoxometalate ionic liquid (POM-IL) gels were synthesized and studied with a
      focus on the correlation between their physicochemical properties and their
      chemical structure. The products were successfully characterized by IR, UV, XRD
      and TG-DTA, and their ionic conductivities were measured. The Keggin-type
      heteropolyanion clusters decorated with long alkyl chains demonstrated a tendency
      to exhibit a gel state at room temperature, while all the gels transformed into
      liquids after heating and then recovered after cooling. With a decrease in the
      alkyl chain length, a significant improvement in the thermal stability and
      conductivity of the ammonium-based POM-IL gels can be achieved. Moreover,
      compared with the corresponding ammonium compound, phosphonium-based POM-IL gel
      was found to be more stable at high temperature and exhibited better
      conductivity. 

PMID- 25947076
TI  - Unusual locations of hydatid disease: a 33 year's experience analysis on 233
      patients.
AB  - Hydatid disease is caused by the tapeworm Echinococcus granulosus and it is an
      endemic parasitic disease of the Mediterranean countries. Although the liver is
      the most involved organ by this disease, hydatidosis can be found anywhere in the
      human body. Rare forms of location may pose diagnostic and therapeutic dilemmas.
      Herein we report our experience with unusual located hydatid disease diagnosed
      and treated at our center the last 33 years. A total of 233 patients were treated
      for echinococcosis (91 males: 39% and 142 females: 61%) between 1980 and 2013 at
      our center. 18 of them (7, 8%) with uncommon located hydatid disease, were
      analyzed retrospectively. 18 patients (8 males and 10 females) were presented
      with unusual location of hydatid disease in our series. Two of them had only
      extrahepatic cysts (0, 9%). A total of 64 hydatid cysts with unusual location
      were analyzed. The most prevalent extrahepatic sites were peritoneal cavity and
      spleen. Total cystectomy with or without tube drainage or omentopexy was
      performed for hydatid cysts of the peritoneal cavity in our series. Splenectomy
      was performed in all cases of splenic hydatidosis. The mean time of post
      operative stay was 16, 3 days (range 7-35 days), morbidity 11% and mortality 5,
      4%. Although echinococcosis is found most often in the liver and lungs, it seems
      that any organ can be involved by this zoonotic disease. The operating surgeon
      must always consider the possibility of unusual location of echinococcal cyst
      when dealing with patients with cystic mass in endemic areas, because any
      misinterpretation may result in unfavorable outcomes.

PMID- 25947077
TI  - Centrifugal step emulsification applied for absolute quantification of nucleic
      acids by digital droplet RPA.
AB  - Aqueous microdroplets provide miniaturized reaction compartments for numerous
      chemical, biochemical or pharmaceutical applications. We introduce centrifugal
      step emulsification for the fast and easy production of monodisperse droplets.
      Homogenous droplets with pre-selectable diameters in a range from 120 MUm to 170
      MUm were generated with coefficients of variation of 2-4% and zero run-in time or
      dead volume. The droplet diameter depends on the nozzle geometry (depth, width,
      and step size) and interfacial tensions only. Droplet size is demonstrated to be
      independent of the dispersed phase flow rate between 0.01 and 1 MUl s(-1),
      proving the robustness of the centrifugal approach. Centrifugal step
      emulsification can easily be combined with existing centrifugal microfluidic unit
      operations, is compatible to scalable manufacturing technologies such as
      thermoforming or injection moulding and enables fast emulsification (>500
      droplets per second and nozzle) with minimal handling effort (2-3 pipetting
      steps). The centrifugal microfluidic droplet generation was used to perform the
      first digital droplet recombinase polymerase amplification (ddRPA). It was used
      for absolute quantification of Listeria monocytogenes DNA concentration standards
      with a total analysis time below 30 min. Compared to digital droplet polymerase
      chain reaction (ddPCR), with processing times of about 2 hours, the overall
      processing time of digital analysis was reduced by more than a factor of 4. 

PMID- 25947075
TI  - Attenuation of EMT in RPE cells and subretinal fibrosis by an RAR-gamma agonist.
AB  - Subretinal fibrosis contributes to the loss of vision associated with age-related
      macular degeneration (AMD). Retinal pigment epithelial (RPE) cells play a key
      role in the pathogenesis of AMD including the fibrotic reaction. We examined the
      role of retinoic acid receptor-gamma (RAR-gamma) in the epithelial-mesenchymal
      transition (EMT) and other fibrosis-related processes in mouse RPE cells cultured
      in a type I collagen gel. Transforming growth factor-beta2 (TGF-beta2)-induced
      collagen gel contraction mediated by the RPE cells was inhibited by the RAR-gamma
      agonist R667 in a concentration- and time-dependent manner. Expression of the
      mesenchymal markers alpha-smooth muscle actin and fibronectin, the release of
      interleukin-6, and the phosphorylation of paxillin, mitogen-activated protein
      kinases (ERK, p38, and JNK), Smad2, and AKT induced by TGF-beta2 were also
      suppressed by the RAR-gamma agonist. Furthermore, gelatin zymography and
      immunoblot analysis revealed that the TGF-beta2-induced release of matrix
      metalloproteinase (MMP)-2, MMP-3, MMP-8, and MMP-9 from RPE cells was inhibited
      by R667, and the MMP inhibitor GM6001 attenuated TGF-beta2-induced RPE cell
      contraction. Finally, immunohistofluorescence analysis with antibodies to glial
      fibrillary acidic protein showed that R667 inhibited the development of
      subretinal fibrosis in a mouse model in vivo. Our results thus suggest that RAR
      gamma agonists may prove effective for the treatment of subretinal fibrosis
      associated with AMD. KEY MESSAGE: RAR-gamma agonist R667 suppressed collagen gel
      contraction mediated by RPE cells. Epithelial-mesenchymal transition (EMT) in RPE
      cells was inhibited by RAR-gamma agonist R667. RAR-gamma agonist R667 inhibited
      fibrosis-related processes in RPE cells. RAR-gamma agonists may attenuate AMD
      associated fibrosis.

PMID- 25947078
TI  - Clinical effects of an optimised care program with telehealth in heart failure
      patients in a community hospital in the Netherlands.
AB  - BACKGROUND: Our hypothesis was that telehealth in combination with an optimised
      care program coordinated amongst care professionals in primary, secondary and
      tertiary care can achieve beneficial outcomes in heart failure. The objective was
      to evaluate the clinical effects of introduction of telehealth in an optimised
      care program in a community hospital in the north of the Netherlands. METHODS: We
      compared the number of unplanned admissions for heart failure in the year before
      and after adding telehealth to the optimised care program. Furthermore, blood
      pressure and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were
      evaluated at baseline and 3, 6 and 12 months after telehealth. Quality of life
      and knowledge about the disease were regularly evaluated via surveys on the
      telehealth system. FINDINGS: The number of unplanned admissions for heart failure
      decreased from on average 1.29 to 0.31 admissions per year after telehealth
      introduction. Blood pressure decreased independent of medication and NT-proBNP
      levels improved as well. Quality of life increased during the telehealth
      intervention and disease knowledge remained high throughout the follow-up period.
      Unplanned admissions that remained after telehealth introduction could be
      accurately predicted at baseline by a multivariate regression model.

PMID- 25947079
TI  - The future of atrial fibrillation therapy: intervention on heat shock proteins
      influencing electropathology is the next in line.
AB  - Atrial fibrillation (AF) is the most common age-related cardiac arrhythmia
      accounting for one-third of hospitalisations. Treatment of AF is difficult, which
      is rooted in the progressive nature of electrical and structural remodelling,
      called electropathology, which makes the atria more vulnerable for AF.
      Importantly, structural damage of the myocardium is already present when AF is
      diagnosed for the first time. Currently, no effective therapy is known that can
      resolve this damage.Previously, we observed that exhaustion of cardioprotective
      heat shock proteins (HSPs) contributes to structural damage in AF patients. Also,
      boosting of HSPs, by the heat shock factor-1 activator geranylgeranylacetone,
      halted AF initiation and progression in experimental cardiomyocyte and dog models
      for AF. However, it is still unclear whether induction of HSPs also prolongs the
      arrhythmia-free interval after, for example, cardioversion of AF.In this review,
      we discuss the role of HSPs in the pathophysiology of AF and give an outline of
      the HALT&REVERSE project, initiated by the HALT&REVERSE Consortium and the AF
      Innovation Platform. This project will elucidate whether HSPs (1) reverse
      cardiomyocyte electropathology and thereby halt AF initiation and progression and
      (2) represent novel biomarkers that predict the outcome of AF conversion and/or
      occurrence of post-surgery AF. 

PMID- 25947080
TI  - The fluorescence regulation mechanism of the paramagnetic metal in a biological
      HNO sensor.
AB  - Paramagnetic metals are frequently used to regulate fluorescence emissions in
      chemical and biological probes. Accurate quantum calculations offer the first
      regulation theory that quenching is through the competitive nonradiative decay of
      the mixed fluorophore/metal (3)pipi*/dd state isoenergetic to the fluorophore
      localized (1)pipi* state. 

PMID- 25947083
TI  - A step closer to the binary: the (1)(infinity)[Bi6I20](2-) anion.
AB  - A series of crown ether based iodidobismuthates was prepared from dibenzo-18
      crown-6 (DB18C6), BiI3 and NaI or KI in acetonitrile (MeCN). The resulting
      compounds [(DB18C6)Na(MeCN)2]4[Bi6I22].2MeCN (1),
      [(DB18C6)Na(MeCN)2]4[Bi8I28].6MeCN (2), [(DB18C6)Na(MeCN)2]2[Bi6I20].3MeCN (3)
      and [(DB18C6)K(MeCN)]4[Bi6I22].2MeCN (4) have been used to explore the templating
      effect of different crown ether based cations and the influence of the I/Bi ratio
      and II interactions on the optical properties of iodidobismuthates. Compound 3
      contains the strand-like anion (1)(infinity)[Bi6I20](2-), which displays a I/Bi
      ratio of 3.33, closer to the binary BiI3 than any other iodidobismuthate.

PMID- 25947081
TI  - Validation of 14-3-3 Protein as a Marker in Sporadic Creutzfeldt-Jakob Disease
      Diagnostic.
AB  - At present, the testing of 14-3-3 protein in cerebrospinal fluid (CSF) is a
      standard biomarker test in suspected sporadic Creutzfeldt-Jakob disease (sCJD)
      diagnosis. Increasing 14-3-3 test referrals in CJD reference laboratories in the
      last years have led to an urgent need to improve established 14-3-3 test methods.
      The main result of our study was the validation of a commercially available 14-3
      3 ELISA next to the commonly used Western blot method as a high-throughput
      screening test. Hereby, 14-3-3 protein expression was quantitatively analyzed in
      CSF of 231 sCJD and 2035 control patients. We obtained excellent
      sensitivity/specificity values of 88 and 96% that are comparable to the
      established Western blot method. Since standard protocols and preanalytical
      sample handling have become more important in routine diagnostic, we investigated
      in a further step the reproducibility and stability of 14-3-3 as a biomarker for
      human prion diseases. Ring trial data from 2009 to 2013 revealed an increase of
      Fleiss' kappa from 0.51 to 0.68 indicating an improving reliability of 14-3-3
      protein detection. The stability of 14-3-3 protein under short-term and long-term
      storage conditions at various temperatures and after repeated freezing/thawing
      cycles was confirmed. Contamination of CSF samples with blood appears likely to
      be an important factor at a concentration of more than 2500 erythrocytes/MUL.
      Hemolysis of erythrocytes with significant release of 14-3-3 protein started
      after 2 days at room temperature. We first define clear standards for the sample
      handling, short- and long-term storage of CSF samples as well as the handling of
      blood- contaminated samples which may result in artificially elevated CSF levels
      of 14-3-3.

PMID- 25947084
TI  - PAI-1 and HER2 interaction in advanced breast cancer disease: evidence for added
      benefit from trastuzumab in HER2-negative patients.
AB  - PURPOSE: The urokinase plasminogen activator (uPA) and the plasminogen activator
      inhibitor 1 (PAI-1) are associated with an aggressive course in breast cancer and
      are used to determine whether chemotherapy is needed in node-negative patients.
      The objective of the study was to evaluate the prognostic value of uPA and PAI-1
      protein expression in advanced breast cancer patients treated with trastuzumab.
      METHODS: Formalin-fixed paraffin-embedded tumor tissue samples were
      retrospectively collected from 230 patients with advanced breast cancer treated
      with trastuzumab and 130 patients treated with 1st line taxanes. uPA, PAI-1, ER,
      PgR, HER2 and Ki67 protein expression was evaluated by immunohistochemistry.
      RESULTS: Central review of HER2 status revealed that only 144 (63 %) of the
      trastuzumab-treated patients were truly HER2-positive. Median survival was 50.7
      months for the HER2-positive and 30.1 months for the HER2-negative patients (p =
      0.006) treated with trastuzumab. In multivariate Cox regression analysis of the
      trastuzumab cohort, a significant interaction was found, in terms of survival,
      between HER2 status and PAI-1 protein expression in the stroma (Wald's p =
      0.002). Positive PAI-1 protein expression in the stroma of HER2-negative patients
      was associated with lower risk of death (HR 0.35, 95 % CI 0.19-0.65, Wald's p =
      0.0008). Such an association was not observed in HER2-positive patients treated
      with trastuzumab or in the non-trastuzumab (validation) cohorts. CONCLUSIONS: Our
      results suggest that positive stromal PAI-1 protein expression may identify a
      subgroup of HER2-negative advanced breast cancer patients who might benefit from
      treatment with trastuzumab. Further studies are warranted to validate these
      findings in larger cohorts.

PMID- 25947082
TI  - Paraquat Induces Cell Death Through Impairing Mitochondrial Membrane
      Permeability.
AB  - Paraquat (PQ) as a Parkinsonian mimetic has been demonstrated to impair
      dopaminergic (DAergic) neurons and is highly correlated with the etiology of
      Parkinson's disease (PD) where the death of DAergic neurons has been mainly
      attributed to impaired mitochondrial functioning. In this study, PQ-induced
      cytotoxicity focusing on mitochondrial membrane permeability (MMP), which has
      been implicated to play a part in neurodegeneration, was investigated. Primarily,
      PQ-induced cytotoxicity and reactive oxygen species (ROS) were inhibited by an
      inhibitor of NADPH oxidase (NOX), indicating the toxic effect of PQ redox
      cycling. Further, dibucaine and cyclosporin A which respectively inhibit
      mitochondrial apoptosis-induced channels (MAC) and mitochondrial permeability
      transition pores (mPTP) were used and found to prevent PQ-induced mitochondrial
      dysfunction, such as decreased mitochondrial membrane potential and increased
      MMP, mitochondrial ROS, and pro-apoptotic factor release. Knockdown of bax and/or
      bak blocked PQ-induced mitochondrial clusterization of Bax and/or Bak and
      cytotoxicity, demonstrating the significance of MAC which is composed of Bax
      and/or Bak. This clusterization coincided with the release of mitochondrial
      apoptotic factors before there was an increase in inner MMP, indicating that MAC
      may precede mPTP formation. Besides, NOX inhibitor but not dibucaine attenuated
      the earlier PQ-induced cytosolic ROS formation or Bax and/or Bak clusterization
      indicating PQ redox cycling may account for MAC formation. In this model, we have
      resolved for the first that PQ cytotoxicity through redox cycling may
      sequentially result in increased outer (MAC) and inner (mPTP) MMP and suggested
      MMP could be implicated as a therapeutic target in treating neurodegenerative
      diseases like PD. 

PMID- 25947085
TI  - The newly synthesized 2-arylnaphthyridin-4-one, CSC-3436, induces apoptosis of
      non-small cell lung cancer cells by inhibiting tubulin dynamics and activating
      CDK1.
AB  - PURPOSE: To investigate the anticancer therapeutic potential of a new synthetic
      compound, 2-(3-hydroxyphenyl)-5-methylnaphthyridin-4-one (CSC-3436), on non-small
      cell lung cancer (NSCLC) cells. METHODS: Cell viability was determined by MTT
      assay. Cell cycle distribution was assessed by propidium iodide staining and
      subjected to flow cytometry analysis. Protein expression was detected by western
      blot analysis. Pharmacological inhibitors and shRNAs were applied to examine the
      possible pathways involved CSC-3436-inhibited viability of NSCLC cells. RESULTS:
      CSC-3436 decreased NSCLC cell viability by inducing apoptosis. In vivo and in
      vitro tubulin polymerization assays revealed that CSC-3463 caused tubulin
      depolymerization by directly binding to the colchicine-binding site. Furthermore,
      CSC-3436 caused the mitotic arrest with a marked activation of cyclin-dependent
      kinase 1 (CDK1) and increased the expression of phospho-Ser/Thr-Pro mitotic
      protein monoclonal 2. The CDK1 inhibitor, roscovitine, reversed the CSC-3436
      induced upregulation of CDK1 activity as well as the mitotic arrest. DNA damage
      response kinases, including ataxia telangiectasia mutated (ATM), ATM and Rad3
      related, DNA-dependent protein kinase, checkpoint kinase 1, and checkpoint kinase
      2, were phosphorylated and activated by CSC-3436. c-Jun N-terminal kinase was
      activated by CSC-3436 and involved in the regulation of mitotic arrest and
      apoptosis. CSC-3436-induced apoptosis was accompanied by the activation of pro
      apoptotic factors FADD, TRADD, and RIP and the inactivation of anti-apoptotic
      proteins Bcl-2 and Bcl-xL, resulting in the cleavage and subsequent activation of
      caspases. CONCLUSIONS: Our results reveal the cellular events in which CSC-3436
      induces tumor cell death and demonstrate that CSC-3436 is a potential tubulin
      disrupting agent for antitumor therapy against NSCLC.

PMID- 25947086
TI  - Visual illusions in predator-prey interactions: birds find moving patterned prey
      harder to catch.
AB  - Several antipredator strategies are related to prey colouration. Some colour
      patterns can create visual illusions during movement (such as motion dazzle),
      making it difficult for a predator to capture moving prey successfully.
      Experimental evidence about motion dazzle, however, is still very scarce and
      comes only from studies using human predators capturing moving prey items in
      computer games. We tested a motion dazzle effect using for the first time natural
      predators (wild great tits, Parus major). We used artificial prey items bearing
      three different colour patterns: uniform brown (control), black with elongated
      yellow pattern and black with interrupted yellow pattern. The last two resembled
      colour patterns of the aposematic, polymorphic dart-poison frog Dendrobates
      tinctorius. We specifically tested whether an elongated colour pattern could
      create visual illusions when combined with straight movement. Our results,
      however, do not support this hypothesis. We found no differences in the number of
      successful attacks towards prey items with different patterns
      (elongated/interrupted) moving linearly. Nevertheless, both prey types were
      significantly more difficult to catch compared to the uniform brown prey,
      indicating that both colour patterns could provide some benefit for a moving
      individual. Surprisingly, no effect of background (complex vs. plain) was found.
      This is the first experiment with moving prey showing that some colour patterns
      can affect avian predators' ability to capture moving prey, but the mechanisms
      lowering the capture rate are still poorly understood. 

PMID- 25947087
TI  - Congenital nephrotic syndrome with dysmorphic features and death in early
      infancy: Questions.

PMID- 25947088
TI  - Identification of candidate MLO powdery mildew susceptibility genes in cultivated
      Solanaceae and functional characterization of tobacco NtMLO1.
AB  - Specific homologs of the plant Mildew Locus O (MLO) gene family act as
      susceptibility factors towards the powdery mildew (PM) fungal disease, causing
      significant economic losses in agricultural settings. Thus, in order to obtain PM
      resistant phenotypes, a general breeding strategy has been proposed, based on the
      selective inactivation of MLO susceptibility genes across cultivated species. In
      this study, PCR-based methodologies were used in order to isolate MLO genes from
      cultivated solanaceous crops that are hosts for PM fungi, namely eggplant, potato
      and tobacco, which were named SmMLO1, StMLO1 and NtMLO1, respectively. Based on
      phylogenetic analysis and sequence alignment, these genes were predicted to be
      orthologs of tomato SlMLO1 and pepper CaMLO2, previously shown to be required for
      PM pathogenesis. Full-length sequence of the tobacco homolog NtMLO1 was used for
      a heterologous transgenic complementation assay, resulting in its
      characterization as a PM susceptibility gene. The same assay showed that a single
      nucleotide change in a mutated NtMLO1 allele leads to complete gene loss-of
      function. Results here presented, also including a complete overview of the
      tobacco and potato MLO gene families, are valuable to study MLO gene evolution in
      Solanaceae and for molecular breeding approaches aimed at introducing PM
      resistance using strategies of reverse genetics. 

PMID- 25947089
TI  - Transgenic plants over-expressing insect-specific microRNA acquire insecticidal
      activity against Helicoverpa armigera: an alternative to Bt-toxin technology.
AB  - The success of Bt transgenics in controlling predation of crops has been tempered
      by sporadic emergence of resistance in targeted insect larvae. Such emerging
      threats have prompted the search for novel insecticidal molecules that are
      specific and could be expressed through plants. We have resorted to small RNA
      based technology for an investigative search and focused our attention to an
      insect-specific miRNA that interferes with the insect molting process resulting
      in the death of the larvae. In this study, we report the designing of a vector
      that produces artificial microRNA (amiR), namely amiR-24, which targets the
      chitinase gene of Helicoverpa armigera. This vector was used as transgene in
      tobacco. Northern blot and real-time analysis revealed the high level expression
      of amiR-24 in transgenic tobacco plants. Larvae feeding on the transgenic plants
      ceased to molt further and eventually died. Our results demonstrate that
      transgenic tobacco plants can express amiR-24 insectice specific to H. armigera. 

PMID- 25947090
TI  - Recurrent Angina Due to Epicardial Coronary Artery Spasm After Successful
      Bioresorbable Vascular Scaffold Implantation.

PMID- 25947091
TI  - Ninjurin1 - a novel regulator of angiogenesis mediated by pericytes - .

PMID- 25947092
TI  - Not all density functionals are created equal: the case of the missing electron
      in the oxidized [W-W=O](7+) core.
AB  - The location of the unpaired electron in the new mixed-valent (W2)(IV,V)
      trication [W2O(dpa)4](3+) presents a challenge for DFT methods. EPR spectroscopy
      confirms the unpaired electron to be in the W(V)-oxo unit, in agreement with the
      predictions of hybrid functionals B3LYP and TPSSh, but contrary to the
      predictions of non-hybrid functionals.

PMID- 25947093
TI  - "Publish or perish"-presentations at annual national orthopaedic meetings and
      their correlation with subsequent publication.
AB  - BACKGROUND: Presentation of research at annual national orthopaedic conferences
      not only serves as a forum for the dissemination of knowledge but is also often a
      requirement of orthopaedic training programmes. The expected outcome is
      publication in a peer-reviewed journal. However, publication rates vary for a
      variety of reasons. The objective of this study was to determine publication
      rates of presentations from our local Singapore Orthopaedic Association (SOA)
      annual scientific meeting (ASM) and some of the potential associated factors. We
      also compared our findings to equivalent meetings worldwide to assess value of
      scientific content of various orthopaedic conferences. METHODS: All presentations
      of six SOA ASMs were entered into a database. Using presentation titles, author
      names and keywords in PubMed and Google Scholar, we determined how many
      presentations progressed to publication in a peer-reviewed journal. Various
      comparisons were made to determine factors that could influence publication
      rates. A comparison with national orthopaedic meetings of America, United
      Kingdom, Ireland, Australia, Germany, Turkey and Brazil was also conducted.
      RESULTS: Excluding the ASMs with less than 4 years of follow-up, the publication
      rate was 35.8%. Both podium and international presenters were found to have
      significantly higher publication rates than poster and local presenters,
      respectively, while basic science and clinical research were found to have
      equivalent rates. Publication rates from other countries' national conferences
      ranged between 26.6% and 58.1%. CONCLUSIONS: We suggest that the quality of a
      presentation is related to its subsequent publication in a peer-reviewed journal.
      Our findings support the general consensus that the annual meeting of the
      American Academy of Orthopaedic Surgeons (AAOS) is the gold standard for the
      dissemination of orthopaedic knowledge updates and advancements in our specialty.
      Each national orthopaedic association could determine the ratio of "presentations
      at ASM" to "publication within five years of presentation" and use this as a
      measure of their annual conference's impact on the addition and advancement to
      the orthopaedic literature. This tool may in turn assist clinicians in
      determining which meetings to attend.

PMID- 25947094
TI  - Medicines availability for non-communicable diseases: the case for standardized
      monitoring.
AB  - BACKGROUND: In response to the global burden of non-communicable diseases (NCDs),
      the World Health Organization (WHO) has developed a Global Action Plan that
      includes a voluntary medicines target of 80% availability and affordability of
      essential medicines for the prevention and treatment of diabetes, cardiovascular
      disease and respiratory disease both in public and private health facilities.
      Reliable measures of medicines availability are needed to track progress towards
      meeting this target. The results of three studies measuring the availability of
      medicines for hypertension and diabetes conducted in Tanzania in 2012-2013 were
      compared to assess the consistency of the results across the studies. METHODS:
      Availability was defined by observation of the medicine (no minimum quantity) on
      the day of the survey. The three studies involved 24, 107 and 1297 health
      facilities. Estimates of the availability of medicines for hypertension and
      diabetes were compared for medicines availability overall, by managing authority
      (government, mission/faith-based, private-for-profit), by facility level
      (hospital, health centre, dispensary) and by setting (urban, rural). RESULTS:
      Comparisons of the availability of medicines were limited by differences in the
      definitions of the medicines and the classifications of the facilities surveyed.
      Metformin was variously reported as available in 33%, 39%, 46%, and 57% of
      facilities. Glibenclamide availability ranged from 19% to 52%. One study reported
      low levels of insulin availability (9-16% depending on insulin type) compared to
      34% in a second study. Captopril (or angiotensin converting enzyme [ACE]
      inhibitor) availability ranged from 13% to 48%while availability of calcium
      channel blockers was 29% to 57% and beta-blockers 15% to 50%. Trends were similar
      across studies with lower availability in government compared to mission or
      private facilities, in dispensary and health centres compared to hospitals, and
      in rural compared to urban facilities. CONCLUSIONS: All three studies showed
      suboptimal availability of NCD medicines, however the estimates of availability
      differed. Regular monitoring using reproducible methods and measuring key
      medicines must replace ad-hoc studies, small selected samples and differences in
      definitions. Low and middle-income countries need to implement monitoring and
      evaluation systems to track progress towards meeting the NCD medicines target and
      to inform country-level interventions to improve access to NCD medicines.

PMID- 25947095
TI  - Combination of 3D skin surface texture features and 2D ABCD features for improved
      melanoma diagnosis.
AB  - Two-dimensional asymmetry, border irregularity, colour variegation and diameter
      (ABCD) features are important indicators currently used for computer-assisted
      diagnosis of malignant melanoma (MM); however, they often prove to be
      insufficient to make a convincing diagnosis. Previous work has demonstrated that
      3D skin surface normal features in the form of tilt and slant pattern disruptions
      are promising new features independent from the existing 2D ABCD features. This
      work investigates that whether improved lesion classification can be achieved by
      combining the 3D features with the 2D ABCD features. Experiments using a
      nonlinear support vector machine classifier show that many combinations of the 2D
      ABCD features and the 3D features can give substantially better classification
      accuracy than using (1) single features and (2) many combinations of the 2D ABCD
      features. The best 2D and 3D feature combination includes the overall 3D skin
      surface disruption, the asymmetry and all the three colour channel features. It
      gives an overall 87.8 % successful classification, which is better than the best
      single feature with 78.0 % and the best 2D feature combination with 83.1 %. These
      demonstrate that (1) the 3D features have additive values to improve the existing
      lesion classification and (2) combining the 3D feature with all the 2D features
      does not lead to the best lesion classification. The two ABCD features not
      selected by the best 2D and 3D combination, namely (1) the border feature and (2)
      the diameter feature, were also studied in separate experiments. It found that
      inclusion of either feature in the 2D and 3D combination can successfully
      classify 3 out of 4 lesion groups. The only one group not accurately classified
      by either feature can be classified satisfactorily by the other. In both cases,
      they have shown better classification performances than those without the 3D
      feature in the combinations. This further demonstrates that (1) the 3D feature
      can be used to improve the existing 2D-based diagnosis and (2) including the 3D
      feature with subsets of the 2D features can be used in distinguishing different
      benign lesion classes from MM. It is envisaged that classification performance
      may be further improved if different 2D and 3D feature subsets demonstrated in
      this study are used in different stages to target different benign lesion classes
      in future studies. 

PMID- 25947096
TI  - Comparison of Archaeal and Bacterial Diversity in Methane Seep Carbonate Nodules
      and Host Sediments, Eel River Basin and Hydrate Ridge, USA.
AB  - Anaerobic oxidation of methane (AOM) impacts carbon cycling by acting as a
      methane sink and by sequestering inorganic carbon via AOM-induced carbonate
      precipitation. These precipitates commonly take the form of carbonate nodules
      that form within methane seep sediments. The timing and sequence of nodule
      formation within methane seep sediments are not well understood. Further, the
      microbial diversity associated with sediment-hosted nodules has not been well
      characterized and the degree to which nodules reflect the microbial assemblage in
      surrounding sediments is unknown. Here, we conducted a comparative study of
      microbial assemblages in methane-derived authigenic carbonate nodules and their
      host sediments using molecular, mineralogical, and geochemical methods. Analysis
      of 16S rRNA gene diversity from paired carbonate nodules and sediments revealed
      that both sample types contained methanotrophic archaea (ANME-1 and ANME-2) and
      syntrophic sulfate-reducing bacteria (Desulfobacteraceae and Desulfobulbaceae),
      as well as other microbial community members. The combination of geochemical and
      molecular data from Eel River Basin and Hydrate Ridge suggested that some nodules
      formed in situ and captured the local sediment-hosted microbial community, while
      other nodules may have been translocated or may represent a record of conditions
      prior to the contemporary environment. Taken together, this comparative analysis
      offers clues to the formation regimes and mechanisms of sediment-hosted carbonate
      nodules. 

PMID- 25947098
TI  - The European Academy of Paediatric Dentistry and Molar Incisor
      Hypomineralisation.

PMID- 25947097
TI  - Detection of Murine Herpesvirus 68 (MHV-68) in Dermacentor reticulatus Ticks.
AB  - Murid herpesvirus 4 (MuHV 4) strain 68 (MHV-68) is a natural pathogen of murid
      rodents, which serves as hosts to Dermacentor reticulatus ticks. These ticks are
      known to transmit multiple pathogens, which can cause diseases in humans and
      animals. Recently, the detection of MHV-68 antibodies in the blood of animals
      living in the same biotope as virus-infected mice has suggested the role of ticks
      in pathogen circulation in nature. Herein, to identify MHV-68 in D. reticulatus
      ticks, DNA samples from 432 adults were collected at two sites in southwestern
      Slovakia from 2011 to 2014. Samples were examined by polymerase chain reaction
      (PCR), targeting ORF50 of MHV-68. Ignoring season and locality, we have found
      25.9 % of the male and 44.9 % of the female ticks to be positive. Within ticks
      collected in Vojka, 40 % (125/312) became positive, at a rate of approximately
      6.8 times higher in spring than in autumn (66 vs 9.7 %). In addition, in the
      spring, 1.4 times more females were positive than males. Within ticks collected
      in Gabcikovo, 23.3 % (28/120) became positive, with positive females being twice
      as frequent. The infecting virus was identified by analyzing amplified products
      via sequencing and restriction fragment length polymorphism (RFLP) analyses.
      Using an explantation/co-cultivation procedure, we examined the salivary glands,
      intestines, and ovaries of five females for live MHV-68. In all organs of two
      ticks, we identified a virus capable of replication in mammalian cells. This is
      the first report of MHV-68 detection in D. reticulatus ticks and of a live virus
      in their organs. Findings encourage further study to determine whether this
      potential arbovirus, found in salivary glands, is transmissible. It further
      supports the hypothesis regarding the mediating role of ticks in MHV-68
      circulation in nature. 

PMID- 25947099
TI  - The role of anti-angiogenesis in non-small-cell lung cancer: an update.
AB  - Recognition of the vascular endothelial growth factor (VEGF) pathway as a key
      mediator of angiogenesis has led to the clinical study of several VEGF and VEGF
      receptor (VEGFR) targeted therapies in non-small-cell lung cancer (NSCLC). These
      targeted therapies include neutralizing antibodies to VEGF (bevacizumab and
      aflibercept) and VEGFR-2 (ramucirumab) and tyrosine kinase inhibitors (TKIs) with
      selectivity for the VEGFRs. Bevacizumab and ramucirumab are associated with
      survival advantages in the treatment of advanced NSCLC: bevacizumab in the first
      line setting in combination with carboplatin/paclitaxel and ramucirumab in
      combination with docetaxel in the second-line setting. The VEGFR-2 TKIs have been
      associated with responses and improved progression-free survival in selected
      NSCLC settings; however, this level of activity has thus far been insufficient to
      confer significant survival advantages. This review will focus on the current
      state of VEGF targeted therapies in NSCLC. 

PMID- 25947100
TI  - Watchful waiting or induction of labour--a matter of informed choice:
      identification, analysis and critical appraisal of decision aids and patient
      information regarding care options for women with uncomplicated singleton late
      and post term pregnancies: a review.
AB  - BACKGROUND: Decision-making during pregnancy regarding different options of care
      can be difficult, particularly when risks of intervention versus no intervention
      for mother and baby are unclear. Unbiased information and support for decision
      making may be beneficial in these situations. The management of normal
      pregnancies at and beyond term is an example of such a situation. In order to
      determine the need to develop an evidence-based decision aid this paper searches,
      analyses and appraises patient decision aids and patient information leaflets
      regarding care options in cases of late term and post-term pregnancies, including
      complementary and alternative medicine (CAM). METHODS: A literature search was
      carried out in a variety of lay and medical databases. INCLUSION CRITERIA:
      written information related to uncomplicated singleton pregnancies and targeted
      at lay people. Analysis and appraisal of included material by means of quality
      criteria was set up based on the International Patient Decision Aid Standards
      accounting for evidence-basing of CAM options. RESULTS: Inclusion of two decision
      aids and eleven leaflets from four decision aids and sixteen leaflets. One
      decision aid met the quality criteria almost completely, the other one only
      insufficiently despite providing some helpful information. Only one leaflet is of
      good quality, but cannot substitute a decision aid. CONCLUSIONS: There is an
      urgent need for the design of an evidence-based decision aid of good quality for
      late-term or post-term pregnancy, particularly in German language.

PMID- 25947101
TI  - The structure of post-traumatic stress disorder and complex post-traumatic stress
      disorder amongst West Papuan refugees.
AB  - BACKGROUND: The validity of applying the construct of post-traumatic stress
      disorder (PTSD) across cultures has been the subject of contention. Although PTSD
      symptoms have been identified across multiple cultures, questions remain whether
      the constellation represents a coherent construct with an interpretable factor
      structure across diverse populations, especially those naive to western notions
      of mental disorder. An important additional question is whether a constellation
      of Complex-PTSD (C-PTSD) can be identified and if so, whether there are
      distinctions between that disorder and core PTSD in patterns of antecedent
      traumatic events. Our study amongst West Papuan refugees in Papua New Guinea
      (PNG) aimed to examine the factorial structure of PTSD based on the DSM-IV, DSM
      5, ICD-10 and ICD-11 definitions, and C-PTSD according to proposed ICD-11
      criteria. We also investigated domains of traumatic events (TEs) and broader
      psychosocial effects of conflict (sense of safety and injustice) associated with
      the factorial structures identified. METHODS: Culturally adapted measures were
      applied to assess exposure to conflict-related traumatic events (TEs), refugees'
      sense of safety and justice, and symptoms of PTSD and C-PTSD amongst 230 West
      Papuan refugees residing in Port Morseby, PNG. RESULTS: Confirmatory factor
      analysis (CFA) supported a unitary construct of both ICD-10 and ICD-11 PTSD,
      comprising the conventional symptom subdomains of intrusion, avoidance, and
      hyperarousal. In contrast, CFA did not identify a unitary construct underlying C
      PTSD. The interaction of witnessing murders and sense of injustice was associated
      with both the intrusion and avoidance domains of PTSD, but not with the unique
      symptom clusters characterizing C-PTSD. CONCLUSIONS: Our findings support the ICD
      PTSD construct and its three-factor structure in this transcultural refugee
      population. Traumatic experiences of witnessing murder associated with a sense of
      injustice were specifically related to the intrusion and avoidance domains of
      PTSD. The unitary nature of C-PTSD across cultures remains in question.

PMID- 25947102
TI  - Response to commentary by Skinner et al. on Regression to the Mean (RTM) in Burke
      et al.
AB  - This letter is a response to commentary by Skinner et al. on an evaluation by
      Burke et al. of the HealthMPowers program, an elementary-school-based program
      developed to improve child health and wellness. In their commentary, Skinner et
      al. make the criticism that our results for changes in BMI-for-Age Z score were
      simply reflective of Regression to the Mean (RTM). In this response, we show that
      while some of our results are consistent with RTM, with adjustment we do still
      observe some small effects in BMI-for-Age Z score over the course of the school
      year. We conclude that while our evaluation was not definitive, we still believe
      that programs of similar design to HealthMPowers merit further rigorous study. 

PMID- 25947103
TI  - National trends in incidence and outcomes of abdominal aortic aneurysm among
      elderly type 2 diabetic and non-diabetic patients in Spain (2003-2012).
AB  - BACKGROUND: This study aims to describe trends in the rate of abdominal aortic
      aneurysm (AAA) and use of open surgery repair (OSR) and endovascular aneurysm
      repair (EVAR) in elderly patients with and without type 2 diabetes in Spain, 2003
      2012. METHODS: We select all patients with a discharge of AAA using national
      hospital discharge data. Discharges were grouped by diabetes status: type 2
      diabetes and no diabetes. In both groups OSR and EVAR were identified. The
      incidence of discharges attributed to AAA were calculated overall and stratified
      by diabetes status and year. We calculated length of stay (LOHS) and in-hospital
      mortality (IHM). Use of OSR and EVAR were calculated stratified by diabetes
      status. Multivariate analysis was adjusted by age, sex, year, smoking habit and
      comorbidity. RESULTS: From 2003 to 2012, 115,020 discharges with AAA were
      identified. The mean age was 74.91 years and 16.7% suffered type 2 diabetes.
      Rates of discharges due to AAA increased significantly in diabetic patients
      (50.09 in 2003 to 78.23 cases per 100,000 in 2012) and non diabetic subjects
      (69.24 to 78.66). The incidences were higher among those without than those with
      diabetes in all the years studied. The proportion of patients that underwent EVAR
      increased for both groups of patients and the open repair decreased. After
      multivariate analysis we found that LOHS and IHM have improved over the study
      period and diabetic patients had lower IHM than those without diabetes (OR 0.81;
      95%CI 0.76-0.85). CONCLUSIONS: Incidence rates were higher in non-diabetic
      patients. For diabetic and non diabetic patients the use of EVAR has increased
      and open repair seems to be decreasing. IHM and LOHS have improved from 2003 to
      2012. Patients with diabetes had significantly lower mortality.

PMID- 25947104
TI  - Comparative toxicokinetics, absolute oral bioavailability, and biotransformation
      of zearalenone in different poultry species.
AB  - After oral (PO) and intravenous (IV) administration of zearalenone (ZEN) to
      broiler chickens, laying hens, and turkey poults, the mycotoxin was rapidly
      absorbed (Tmax = 0.32-0.97 h) in all three species; however, the absolute oral
      bioavailability was low (F% = 6.87-10.28%). Next, also a rapid elimination of the
      mycotoxin in all poultry species was observed (T(1/2el) = 0.29-0.46 h). Both
      alpha- and beta-zearalenone (ZEL) were formed equally after IV administration in
      all species studied, whereas an increased biotransformation to beta-ZEL was
      demonstrated after PO administration, indicating presystemic biotransformation
      mainly in broiler chickens and laying hens. In comparison to the latter, turkey
      poults demonstrated a more extensive biotransformation of ZEN to alpha-ZEL after
      PO administration which could, in combination with the observed higher volume of
      distribution of ZEN, indicate a higher sensitivity of this species to the effects
      of ZEN in comparison to other poultry species.

PMID- 25947105
TI  - Influence of in situ progressive N-terminal is still controversial truncation of
      glycogen branching enzyme in Escherichia coli DH5alpha on glycogen structure,
      accumulation, and bacterial viability.
AB  - BACKGROUND: Glycogen average chain length (ACL) has been linked with bacterial
      durability, but this was on the basis of observations across different species.
      We therefore wished to investigate the relationship between bacterial durability
      and glycogen ACL by varying glycogen average chain length in a single species. It
      has been shown that progressive shortening of the N-terminus of glycogen
      branching enzyme (GBE) leads to a lengthening of oligosaccharide inter-alpha-1,6
      glycosidic chain lengths, so we sought to harness this to create a set of
      Escherichia coli DH5alpha strains with a range of glycogen average chain lengths,
      and assess these strains for durability related attributes, such as starvation,
      cold and desiccation stress resistance, and biofilm formation. RESULTS: A series
      of Escherichia coli DH5alpha mutants were created with glgB genes that were in
      situ progressively N-terminus truncated. N-terminal truncation shifted the
      distribution of glycogen chain lengths from 5-11 DP toward 13-50 DP, but the
      relationship between glgB length and glycogen ACL was not linear. Surprisingly,
      removal of the first 270 nucleotides of glgB (glgBDelta270) resulted in
      comparatively high glycogen accumulation, with the glycogen having short ACL.
      Complete knockout of glgB led to the formation of amylose-like glycogen
      containing long, linear alpha1,4-glucan chains with significantly reduced
      branching frequency. Physiologically, the set of mutant strains had reduced
      bacterial starvation resistance, while minimally increasing bacterial desiccation
      resistance. Finally, although there were no obvious changes in cold stress
      resistance or biofilm forming ability, one strain (glgBDelta180) had
      significantly increased biofilm formation in favourable media. CONCLUSIONS:
      Despite glgB being the first gene of an operon, it is clear that in situ mutation
      is a viable means to create more biologically relevant mutant strains. Secondly,
      there was the suggestion in the data that impairments of starvation, cold and
      desiccation resistance were worse for the strain lacking glgB, though the first
      of these was not statistically significant. The results provide prima facie
      evidence linking abiotic stress tolerance with shorter glycogen ACL. However,
      further work needs to be done, perhaps in a less labile species. Further work is
      also required to tease out the complex relationship between glycogen abundance
      and glycogen structure.

PMID- 25947106
TI  - The cost-effectiveness of testing strategies for type 2 diabetes: a modelling
      study.
AB  - BACKGROUND: An estimated 850,000 people have diabetes without knowing it and as
      many as 7 million more are at high risk of developing it. Within the NHS Health
      Checks programme, blood glucose testing can be undertaken using a fasting plasma
      glucose (FPG) or a glycated haemoglobin (HbA1c) test but the relative cost
      effectiveness of these is unknown. OBJECTIVES: To estimate and compare the cost
      effectiveness of screening for type 2 diabetes using a HbA1c test versus a FPG
      test. In addition, to compare the use of a random capillary glucose (RCG) test
      versus a non-invasive risk score to prioritise individuals who should undertake a
      HbA1c or FPG test. DESIGN: Cost-effectiveness analysis using the Sheffield Type 2
      Diabetes Model to model lifetime incidence of complications, costs and health
      benefits of screening. SETTING: England; population in the 40-74-years age range
      eligible for a NHS health check. DATA SOURCES: The Leicester Ethnic
      Atherosclerosis and Diabetes Risk (LEADER) data set was used to analyse
      prevalence and screening outcomes for a multiethnic population. Alternative
      prevalence rates were obtained from the literature or through personal
      communication. METHODS: (1) Modelling of screening pathways to determine the cost
      per case detected followed by long-term modelling of glucose progression and
      complications associated with hyperglycaemia; and (2) calculation of the costs
      and health-related quality of life arising from complications and calculation of
      overall cost per quality-adjusted life-year (QALY), net monetary benefit and the
      likelihood of cost-effectiveness. RESULTS: Based on the LEADER data set from a
      multiethnic population, the results indicate that screening using a HbA1c test is
      more cost-effective than using a FPG. For National Institute for Health and Care
      Excellence (NICE)-recommended screening strategies, HbA1c leads to a cost saving
      of L12 and a QALY gain of 0.0220 per person when a risk score is used as a
      prescreen. With no prescreen, the cost saving is L30 with a QALY gain of 0.0224.
      Probabilistic sensitivity analysis indicates that the likelihood of HbA1c being
      more cost-effective than FPG is 98% and 95% with and without a risk score,
      respectively. One-way sensitivity analyses indicate that the results based on
      prevalence in the LEADER data set are insensitive to a variety of alternative
      assumptions. However, where a region of the country has a very different joint
      HbA1c and FPG distribution from the LEADER data set such that a FPG test yields a
      much higher prevalence of high-risk cases relative to HbA1c, FPG may be more cost
      effective. The degree to which the FPG-based prevalence would have to be higher
      depends very much on the uncertain relative uptake rates of the two tests. Using
      a risk score such as the Leicester Practice Database Score (LPDS) appears to be
      more cost-effective than using a RCG test to identify individuals with the
      highest risk of diabetes who should undergo blood testing. LIMITATIONS: We did
      not include rescreening because there was an absence of required relevant
      evidence. CONCLUSIONS: Based on the multiethnic LEADER population, among
      individuals currently attending NHS Health Checks, it is more cost-effective to
      screen for diabetes using a HbA1c test than using a FPG test. However, in some
      localities, the prevalence of diabetes and high risk of diabetes may be higher
      for FPG relative to HbA1c than in the LEADER cohort. In such cases, whether or
      not it still holds that HbA1c is likely to be more cost-effective than FPG
      depends on the relative uptake rates for HbA1c and FPG. Use of the LPDS appears
      to be more cost-effective than a RCG test for prescreening. FUNDING: The National
      Institute for Health Research Health Technology Assessment programme.

PMID- 25947108
TI  - Corrigendum.

PMID- 25947107
TI  - A Response to Odland et al.'s Misleading, Alarmist Estimates of Risk for
      Overpathologizing when Interpreting the MMPI-2-RF.
AB  - In a recently published article in this journal, Odland, Lammy, Perle, Martin,
      and Grote report Monte Carlo-simulated normative base rates of scale elevations
      on the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2
      RF). Their primary conclusion--reflected in the title of their article--is that
      MMPI-2-RF interpretation is associated with "high risk of pathologizing healthy
      adults" when the 40 substantive scales of the test are simultaneously
      interpreted. In this paper, we describe how their conclusion follows from several
      faulty premises, three of which were already debunked in an earlier article and
      remain false despite counterarguments proposed by Odland and colleagues. We also
      address these authors' misinterpretation of their analyses and, furthermore,
      their premise that MMPI-2-RF interpretive guidelines are flawed because they
      "currently do not account for a basic statistical principle: Type I (or alpha)
      error inflation" (p. 1). This premise is irrelevant to psychological test
      interpretation and misaligned with neuropsychological testing literature cited in
      support of it. Consistent with suggestions by some of the authors they cite, we
      reiterate MMPI-2-RF interpretive guidelines designed to mitigate the impact of
      measurement error (not alpha error) by way of a scientific assessment approach
      that relies on integration of information derived from multiple sources.

PMID- 25947110
TI  - Psychological factors associated with acute and chronic central serous
      chorioretinopathy.
AB  - BACKGROUND: Central serous chorioretinopathy (CSC) has been associated with
      several psychological factors. But previous psychological data are limited and
      mainly restricted to male patients and small sample size. In this study we
      investigated psychosomatic complaints, personality factors, life events, and
      stress coping in acute and chronic recurrent CSC patients. METHODS: Ninety-five
      patients (71 men, 24 women) with either acute or chronic CSC were evaluated
      regarding critical life events before diagnosis, psychosomatic complaints,
      personality traits and coping style. The characteristics of CSC patients were
      compared with a control group comprising 75 patients (46 men, 29 women) suffering
      from acute or chronic ophthalmic disorders other than CSC. RESULTS: Compared with
      patients of the control group, CSC patients reported more psychosomatic problems,
      unfavourable stress coping strategies and critical life events as well as
      elevated tension, aggression, strain, emotional instability and achievement
      orientation. Except for aggression the observed characteristics were more
      pronounced in acute than in chronic CSC patients. CONCLUSIONS: The appearance of
      CSC may be associated with an accumulation of stressful life events with an
      unfavourable coping style and distinctive personality factors. Acute CSC is
      related to more unfavourable stress coping and more physical complaints compared
      to its chronic course. Elevated aggression may imply one potential risk factor
      for CSC manifestation and also may have an adverse effect with its
      chronification.

PMID- 25947111
TI  - Direct Synthesis and Bonding Properties of the First MU(2)-eta(2),eta(2)-Allyl
      Bridged Diiridium Complex.
AB  - The direct synthesis of the first MU(2)-eta(2),eta(2)-allyl-bridged diiridium
      complex ([2](+)), bearing the uncommon counterion [IrCl2(COD)](-) ([3](-)), is
      described. Both bridging moieties in [2](+), namely, allyl and acetate, are
      introduced in a single reaction step from [{IrCl(COD)}2] (1) and allyl acetate. A
      combination of X-ray crystallography and density functional theory calculations
      reveals pronounced metal-allyl pi-back-bonding. 

PMID- 25947109
TI  - Bioactive magnetic near Infra-Red fluorescent core-shell iron oxide/human serum
      albumin nanoparticles for controlled release of growth factors for augmentation
      of human mesenchymal stem cell growth and differentiation.
AB  - BACKGROUND: Iron oxide (IO) nanoparticles (NPs) of sizes less than 50 nm are
      considered to be non-toxic, biodegradable and superparamagnetic. We have
      previously described the generation of IO NPs coated with Human Serum Albumin
      (HSA). HSA coating onto the IO NPs enables conjugation of the IO/HSA NPs to
      various biomolecules including proteins. Here we describe the preparation and
      characterization of narrow size distribution core-shell NIR fluorescent IO/HSA
      magnetic NPs conjugated covalently to Fibroblast Growth Factor 2 (FGF2) for
      biomedical applications. We examined the biological activity of the conjugated
      FGF2 on human bone marrow mesenchymal stem cells (hBM-MSCs). These multipotent
      cells can differentiate into bone, cartilage, hepatic, endothelial and neuronal
      cells and are being studied in clinical trials for treatment of various diseases.
      FGF2 enhances the proliferation of hBM-MSCs and promotes their differentiation
      toward neuronal, adipogenic and osteogenic lineages in vitro. RESULTS: The NPs
      were characterized by transmission electron microscopy, dynamic light scattering,
      ultraviolet-visible spectroscopy and fluorescence spectroscopy. Covalent
      conjugation of the FGF2 to the IO/HSA NPs significantly stabilized this growth
      factor against various enzymes and inhibitors existing in serum and in tissue
      cultures. IO/HSA NPs conjugated to FGF2 were internalized into hBM-MSCs via
      endocytosis as confirmed by flow cytometry analysis and Prussian Blue staining.
      Conjugated FGF2 enhanced the proliferation and clonal expansion capacity of hBM
      MSCs, as well as their adipogenic and osteogenic differentiation to a higher
      extent compared with the free growth factor. Free and conjugated FGF2 promoted
      the expression of neuronal marker Microtubule-Associated Protein 2 (MAP2) to a
      similar extent, but conjugated FGF2 was more effective than free FGF2 in
      promoting the expression of astrocyte marker Glial Fibrillary Acidic Protein
      (GFAP) in these cells. CONCLUSIONS: These results indicate that stabilization of
      FGF2 by conjugating the IO/HSA NPs can enhance the biological efficacy of FGF2
      and its ability to promote hBM-MSC cell proliferation and trilineage
      differentiation. This new system may benefit future therapeutic use of hBM-MSCs.

PMID- 25947112
TI  - The potential role of vitamin D in the link between obesity and asthma
      severity/control in children.
AB  - Childhood obesity and asthma are major public health problems. Obesity is not
      only associated with increased risk of incident asthma, but it may worsen asthma
      severity/control. Although the mechanisms linking obesity with asthma expression
      have not been completely elucidated, evidence suggests that increased frequency
      of acute respiratory infection (ARI) and decreased corticosteroid responsiveness
      may help to explain how obesity worsens asthma expression. In addition, obese
      individuals have low vitamin D status, and emerging evidence suggests vitamin D
      affects risk of ARI and corticosteroid responsiveness in individuals with asthma.
      In this review, we summarize the association between obesity and asthma
      severity/control in children and discuss ARI and corticosteroid responsiveness as
      potential mediators in the obesity-asthma pathway. We also discuss the potential
      role of vitamin D, including a brief summary of recent randomized controlled
      trials of vitamin D supplementation. 

PMID- 25947113
TI  - PNA as a Biosupramolecular Tag for Programmable Assemblies and  Reactions.
AB  - The programmability of oligonucleotide hybridization offers an attractive
      platform for the design of assemblies with emergent properties or functions.
      Developments in DNA nanotechnologies have transformed our thinking about the
      applications of nucleic acids. Progress from designed assemblies to functional
      outputs will continue to benefit from functionalities added to the nucleic acids
      that can participate in reactions or interactions beyond hybridization. In that
      respect, peptide nucleic acids (PNAs) are interesting because they combine the
      hybridization properties of DNA with the modularity of peptides. In fact, PNAs
      form more stable duplexes with DNA or RNA than the corresponding natural
      homoduplexes. The high stability achieved with shorter oligomers (an 8-mer is
      sufficient for a stable duplex at room temperature) typically results in very
      high sequence fidelity in the hybridization with negligible impact of the ionic
      strength of the buffer due to the lack of electrostatic repulsion between the
      duplex strands. The simple peptidic backbone of PNA has been shown to be tolerant
      of modifications with substitutions that further enhance the duplex stability
      while providing opportunities for functionalization. Moreover, the metabolic
      stability of PNAs facilitates their integration into systems that interface with
      biology. Over the past decade, there has been a growing interest in using PNAs as
      biosupramolecular tags to program assemblies and reactions. A series of robust
      templated reactions have been developed with functionalized PNA. These reactions
      can be used to translate DNA templates into functional polymers of unprecedented
      complexity, fluorescent outputs, or bioactive small molecules. Furthermore,
      cellular nucleic acids (mRNA or miRNA) have been harnessed to promote assemblies
      and reactions in live cells. The tolerance of PNA synthesis also lends itself to
      the encoding of small molecules that can be further assembled on the basis of
      their nucleic acid sequences. It is now well-established that hybridization-based
      assemblies displaying two or more ligands can interact synergistically with a
      target biomolecule. These assemblies have now been shown to be functional in
      vivo. Similarly, PNA-tagged macromolecules have been used to prepare bioactive
      assemblies and three-dimensional nanostructures. Several technologies based on
      DNA-templated synthesis of sequence-defined polymers or DNA-templated display of
      ligands have been shown to be compatible with reiterative cycles of
      selection/amplification starting with large libraries of DNA templates, bringing
      the power of in vitro evolution to synthetic molecules and offering the
      possibility of exploring uncharted molecular diversity space with unprecedented
      scope and speed.

PMID- 25947115
TI  - Personalized gene therapy locks out HIV, paving the way to control virus without
      antiretroviral drugs.
AB  - INTRODUCTION: Advances in adoptive immunotherapy have enabled gene therapy
      approaches to be tested in clinical trials that involve the transfer of
      engineered immune cells to specifically target HIV-infected cells or block HIV
      infection or transmission. Genetic editing through engineered targeted nucleases
      provides a method for producing cells that are permanently resistant to HIV.
      AREAS COVERED: Here, we discuss current and developing gene therapy approaches
      aimed to confer resistance to HIV infection at the cellular level by targeting
      viral or cellular elements, with a focus on gene editing strategies that target
      viral entry. Human gene therapy trials in HIV infection are reviewed. EXPERT
      OPINION: In concept, a single infusion of genetically modified cells could
      potentially reduce the need for lifelong medication by providing long-term
      control over the virus (functional immunity). While the dream of completely
      eliminating viral reservoirs (sterilizing immunity) is appealing, this presents a
      significant additional hurdle and may not be necessary to improve long-term
      health. A single infusion, or a small number of infusions, of engineered cells
      may be shown in confirmatory clinical trials to produce a meaningful biologic
      effect. These techniques have implications for targeted gene therapy in HIV and
      other diseases.

PMID- 25947114
TI  - Characterization and noninvasive diagnosis of bladder cancer with serum surface
      enhanced Raman spectroscopy and genetic algorithms.
AB  - This study aims to characterize and classify serum surface-enhanced Raman
      spectroscopy (SERS) spectra between bladder cancer patients and normal volunteers
      by genetic algorithms (GAs) combined with linear discriminate analysis (LDA). Two
      group serum SERS spectra excited with nanoparticles are collected from healthy
      volunteers (n = 36) and bladder cancer patients (n = 55). Six diagnostic Raman
      bands in the regions of 481-486, 682-687, 1018-1034, 1313-1323, 1450-1459 and
      1582-1587 cm(-1) related to proteins, nucleic acids and lipids are picked out
      with the GAs and LDA. By the diagnostic models built with the identified six
      Raman bands, the improved diagnostic sensitivity of 90.9% and specificity of 100%
      were acquired for classifying bladder cancer patients from normal serum SERS
      spectra. The results are superior to the sensitivity of 74.6% and specificity of
      97.2% obtained with principal component analysis by the same serum SERS spectra
      dataset. Receiver operating characteristic (ROC) curves further confirmed the
      efficiency of diagnostic algorithm based on GA-LDA technique. This exploratory
      work demonstrates that the serum SERS associated with GA-LDA technique has
      enormous potential to characterize and non-invasively detect bladder cancer
      through peripheral blood. 

PMID- 25947116
TI  - Isolated pharyngeal swallow exists during normal human feeding.
AB  - Swallowing is one of the basic activities in humans. The pharynx functions as an
      airway and a food channel, and a pharyngeal swallow usually occurs after bolus
      transport from the oral cavity. However, direct fluid infusion through a catheter
      into the hypopharynx produces a pharyngeal swallow without the oral stage in
      experimental situations. The purpose of this study was to examine whether a
      pharyngeal swallow, which is not accompanied by bolus transport, can occur during
      normal human feeding. Fifty-three healthy volunteers (25-89 years) were recorded,
      via videofluoroscopic examination of swallowing, during 3 different swallowing
      trials: command swallow of 10 ml liquid barium, chew-swallow of corned beef, and
      chew-swallow of a mixture of corned beef and liquid barium. Subsequently each
      swallow was classified as being either a consecutive pharyngeal swallow (CPS),
      following transport, or an isolated pharyngeal swallow (IPS), without immediately
      prior transport. The location of the bolus at swallow initiation was also noted.
      Of 307 trials, 681 swallows were identified, which included 43 IPS and 638 CPS.
      IPS only occurred as the first swallow of a trial, but the frequency of IPS did
      not differ between 28 younger (< 60 years) and 25 older (>= 60 years) people. Of
      the three food types, IPS occurred more frequently with the mixed food than with
      liquid. These results suggest that IPS may represent an airway protective
      mechanism. In conclusion, IPS occurs in normal swallowing during a daily eating
      situation. Swallowing is more complex than a simple reflex. 

PMID- 25947117
TI  - DRAPA trial--closed-suction drains versus closed gravity drains in pancreatic
      surgery: study protocol for a randomized controlled trial.
AB  - BACKGROUND: The morbidity of pancreatic resection remains high, with pancreatic
      fistula being the most common cause. The important question is whether any
      postoperative treatment adjustment may prevent the development of clinically
      significant postoperative pancreatic fistulae. Recent studies have shown that
      intraabdominal drains and manipulation using them are of great importance.
      Although authors of a few retrospective reports have described good results of
      pancreatic resection without the use of intraabdominal drains, a recent
      prospective randomized trial showed that routine elimination of drains in
      pancreaticoduodenectomy is associated with poor outcome. An important issue
      arises as to which type of drain is most suitable for pancreatic resection. Two
      types of surgical drains exist: open drains and closed drains. Open drains are
      considered obsolete nowadays because of frequent retrograde infection. Closed
      drains include two types: passive gravity drains and closed-suction drains.
      Closed-suction drains are more effective, as they remove fluid from the abdominal
      cavity under light pressure. However, some surgeons believe that closed-suction
      drains represent a potential hazard to patients and that negative pressure might
      increase the risk of pancreatic fistulae. Nobody has yet specifically dealt with
      the question of which kind of drainage is most appropriate in pancreatic surgery.
      METHODS/DESIGN: The aim of the DRAins in PAncreatic surgery (DRAPA) trial is to
      compare the closed-suction drain versus the closed passive gravity drain in
      pancreatic resection. DRAPA is a dual-centre, prospective, randomized controlled
      trial. The primary endpoint is the rate of postoperative pancreatic fistula; the
      secondary endpoint is postoperative morbidity with follow-up of 3 months.
      DISCUSSION: No study to date has compared different types of drains in pancreatic
      surgery. This study is designed to answer the question whether any particular
      type of drain might lower the rate of postoperative pancreatic fistula or other
      complications. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01988519.
      Registered 13 November 2013.

PMID- 25947118
TI  - Subwavelength-thick lenses with high numerical apertures and large efficiency
      based on high-contrast transmitarrays.
AB  - Flat optical devices thinner than a wavelength promise to replace conventional
      free-space components for wavefront and polarization control. Transmissive flat
      lenses are particularly interesting for applications in imaging and on-chip
      optoelectronic integration. Several designs based on plasmonic metasurfaces, high
      contrast transmitarrays and gratings have been recently implemented but have not
      provided a performance comparable to conventional curved lenses. Here we report
      polarization-insensitive, micron-thick, high-contrast transmitarray micro-lenses
      with focal spots as small as 0.57 lambda. The measured focusing efficiency is up
      to 82%. A rigorous method for ultrathin lens design, and the trade-off between
      high efficiency and small spot size (or large numerical aperture) are discussed.
      The micro-lenses, composed of silicon nano-posts on glass, are fabricated in one
      lithographic step that could be performed with high-throughput photo or
      nanoimprint lithography, thus enabling widespread adoption. 

PMID- 25947119
TI  - Second letter to editor in response to author response published in J. Air Waste
      Manage. Assoc. 64: 1218-1220.

PMID- 25947120
TI  - Author response to second letter to the editor, J. Air Waste Manage. Assoc. 65:
      245-246.

PMID- 25947121
TI  - Evaluation of assumptions for estimating chemical light extinction at U.S.
      national parks.
AB  - Studies were conducted at Great Smoky Mountains National Park (NP) (GRSM),
      Tennessee, Mount Rainier NP (MORA), Washington, and Acadia NP (ACAD), Maine, to
      evaluate assumptions used to estimate aerosol light extinction from chemical
      composition. The revised IMPROVE equation calculates light scattering from
      concentrations of PM2.5 sulfates, nitrates, organic carbon mass (OM), and soil.
      Organics are assumed to be nonhygroscopic. Organic carbon (OC) is converted to OM
      with a multiplier of 1.8. Experiments were conducted to evaluate assumptions on
      aerosol hydration state, the OM/OC ratio, OM hygroscopicity, and mass scattering
      efficiencies. Sulfates were neutralized by ammonium during winter at GRSM (W,
      winter) and at MORA during summer but were acidic at ACAD and GRSM (S, summer)
      during summer. Hygroscopic growth was mostly smooth and continuous, rarely
      exhibiting hysteresis. Deliquescence was not observed except infrequently during
      winter at GRSM (W). Water-soluble organic carbon (WSOC) was separated from bulk
      OC with solid-phase absorbents. The average OM/OC ratios were 2.0, 2.7, 2.1, and
      2.2 at GRSM (S), GRSM (W), MORA, and ACAD, respectively. Hygroscopic growth
      factors (GF) at relative humidity (RH) 90% for aerosols generated from WSOC
      extracts averaged 1.19, 1.06, 1.13, and 1.16 at GRSM (S), GRSM (W), MORA, and
      ACAD, respectively. Thus, the assumption that OM is not hygroscopic may lead to
      underestimation of its contribution to light scattering. IMPLICATIONS: Studies at
      IMPROVE sites conducted in U.S. national parks showed that aerosol organics
      comprise more PM2.5 mass and absorb more water as a function of relative humidity
      than is currently assumed by the IMPROVE equation for calculating chemical light
      extinction. Future strategies for reducing regional haze may therefore need to
      focus more heavily on understanding the origins and control of anthropogenic
      sources of organic aerosols.

PMID- 25947122
TI  - Effect of interferents on the performance of direct-reading organic vapor
      monitors.
AB  - Direct-reading organic vapor monitors are often used to measure volatile organic
      compound concentrations in complex chemical gas mixtures. However, there is a
      paucity of data on the impact of multiple gases on monitor performance, even
      though it is known that monitor sensitivity may vary by chemical. This study
      investigated the effects of interferents on the performance of the MIRAN SapphIRe
      Portable Ambient Air Analyzer (SAP) and Century Portable Toxic Vapor Analyzer
      (TVA-1000) when sampling a specific agent of interest (cyclohexane). The TVA-1000
      contained a dual detector: a photoionization detector (PID) and a flame
      ionization detector (FID). Three devices of each monitor were challenged with
      different combinations of cyclohexane and potential interferent vapors (hexane,
      methyl ethyl ketone, trichloroethylene, and toluene) at 21 degrees C and 90%
      relative humidity (RH), an extreme environmental condition. Five replicates at
      four target concentrations were tested: 30, 150, 300, and 475 ppm. Multiple
      proportions of cyclohexane to interferent enabled the determination of the
      interferent effect on monitor performance. The monitor concentrations were
      compared to reference concentrations measured using NIOSH Method 1500. Three
      scenarios were investigated: no response factor, cyclohexane response factor, and
      weighted-mixed response factor applied. False negatives occurred more frequently
      for PID (21.1%), followed by FID (4.8%) and SAP (0.2%). Measurements from all
      monitors generally had a positive bias compared to the reference measurements.
      Some monitor measurements exceeded twice the reference concentrations: PID
      (36.8%), SAP (19.8%), and FID (6.3%). Evaluation of the 95% confidence intervals
      indicated that performance of all monitors varied by concentration. In addition,
      the performance of the PID and SAP varied by presence of an interfering compound,
      especially toluene and hexane for the PID and trichloroethylene for the SAP.
      Variability and bias associated with all these monitors preclude supplanting
      traditional sorbent-based tube methods for measuring volatile organic compounds
      (VOCs), especially for compliance monitoring. IMPLICATIONS: Industrial hygienists
      need to use care when using any of the three monitor detection types to measure
      the concentration of unknown chemical mixtures. Monitor performance is affected
      by the presence of interferents. Application of manufacturer recommended response
      factors may not adequately scale measurements to minimize monitor bias when
      compared to standard reference methods. Users should calibrate their monitors to
      a known reference method prior to use, if possible. Each of the monitors has its
      own limitations, which should be considered to ensure quality measurements are
      reported.

PMID- 25947123
TI  - Chemical reactivities of ambient air samples in three Southern California
      communities.
AB  - The potential adverse health effects of PM2.5 (particulate matter with an
      aerodynamic diameter<2.5 MUm) and vapor samples from three communities that
      neighbor railyards, Commerce (CM), Long Beach (LB), and San Bernardino (SB), were
      assessed by determination of chemical reactivities attributed to the induction of
      oxidative stress by air pollutants. The assays used were dithiothreitol (DTT)-
      and dihydrobenzoic acid (DHBA)-based procedures for prooxidant content and a
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) assay for electrophiles.
      Prooxidants and electrophiles have been proposed as the reactive chemical species
      responsible for the induction of oxidative stress by air pollution mixtures. The
      PM2.5 samples from CM and LB sites showed seasonal differences in reactivities,
      with higher levels in the winter, whereas the SB sample differences were
      reversed. The reactivities in the vapor samples were all very similar, except for
      the summer SB samples, which contained higher levels of both prooxidants and
      electrophiles. The results suggest that the observed reactivities reflect general
      geographical differences rather than direct effects of the railyards.
      Distributional differences in reactivities were also observed, with PM2.5
      fractions containing most of the prooxidants (74-81%) and the vapor phase most of
      the electrophiles (82-96%). The high levels of the vapor-phase electrophiles and
      their potential for adverse biological effects point out the importance of the
      vapor phase in assessing the potential health effects of ambient air.
      IMPLICATIONS: PM2.5 and its corresponding vapor phase, containing semivolatile
      organics, were collected in three communities in the Los Angeles Basin and
      examined with toxicologically relevant chemical assays. The PM2.5 phase contained
      most of the prooxidants and the vapor phase contained most of the electrophiles,
      whose content was highest in summer samples from a receptor site that reflected
      greater photochemical processing of the air parcel during its transport. As
      electrophiles initiate both adverse and adaptive responses to foreign substances
      by biological systems, their presence in the vapor phase emphasizes the
      importance of this phase in the overall health effects of ambient air.

PMID- 25947124
TI  - A study of the impact of moist-heat and dry-heat treatment processes on hazardous
      trace elements migration in food waste.
AB  - Using laboratory experiments, the authors investigated the impact of dry-heat and
      moist-heat treatment processes on hazardous trace elements (As, Hg, Cd, Cr, and
      Pb) in food waste and explored their distribution patterns for three waste
      components: oil, aqueous, and solid components. The results indicated that an
      insignificant reduction of hazardous trace elements in heat-treated waste-0.61
      14.29% after moist-heat treatment and 4.53-12.25% after dry-heat treatment-and a
      significant reduction in hazardous trace elements (except for Hg without external
      addition) after centrifugal dehydration (P < 0.5). Moreover, after heat
      treatment, over 90% of the hazardous trace elements in the waste were detected in
      the aqueous and solid components, whereas only a trace amount of hazardous trace
      elements was detected in the oil component (<0.01%). In addition, results
      indicated that heat treatment process did not significantly reduce the
      concentration of hazardous trace elements in food waste, but the separation
      process for solid and aqueous components, such as centrifugal dehydration, could
      reduce the risk considerably. Finally, combined with the separation technology
      for solid and liquid components, dry-heat treatment is superior to moist-heat
      treatment on the removal of external water-soluble ionic hazardous trace
      elements. IMPLICATIONS: An insignificant reduction of hazardous trace elements in
      heat-treated waste showed that heat treatment does not reduce trace elements
      contamination in food waste considerably, whereas the separation process for
      solid and aqueous components, such as centrifugal dehydration, could reduce the
      risk significantly. Moreover, combined with the separation technology for solid
      and liquid components, dry-heat treatment is superior to moist-heat treatment for
      the removal of external water-soluble ionic hazardous trace elements, by
      exploring distribution patterns of trace elements in three waste components: oil,
      aqueous, and solid components.

PMID- 25947125
TI  - Composition and sources of fine and coarse particles collected during 2002-2010
      in Boston, MA.
AB  - Identifying the sources, composition, and temporal variability of fine (PM2.5)
      and coarse (PM2.5-10) particles is a crucial component in understanding
      particulate matter (PM) toxicity and establishing proper PM regulations. In this
      study, a Harvard Impactor was used to collect daily integrated fine and coarse
      particle samples every third day for 9 years at a single site in Boston, MA. In
      total, 1,960 filters were analyzed for elements, black carbon (BC), and total PM
      mass. Positive Matrix Factorization (PMF) was used to identify source types and
      quantify their contributions to ambient PM2.5 and PM2.5-10. BC and 17 elements
      were identified as the main constituents in our samples. Results showed that BC,
      S, and Pb were associated exclusively with the fine particle mode, while 84% of V
      and 79% of Ni were associated with this mode. Elements mostly found in the coarse
      mode, over 80%, included Ca, Mn (road dust), and Cl (sea salt). PMF identified
      six source types for PM2.5 and three source types for PM2.5-10. Source types for
      PM2.5 included regional pollution, motor vehicles, sea salt, crustal/road dust,
      oil combustion, and wood burning. Regional pollution contributed the most,
      accounting for 48% of total PM2.5 mass, followed by motor vehicles (21%) and wood
      burning (19%). Source types for PM2.5-10 included crustal/road dust (62%), motor
      vehicles (22%), and sea salt (16%). A linear decrease in PM concentrations with
      time was observed for both fine (-5.2%/yr) and coarse (-3.6%/yr) particles. The
      fine-mode trend was mostly related to oil combustion and regional pollution
      contributions. Average PM2.5 concentrations peaked in summer (10.4 ug/m3), while
      PM2.5-10 concentrations were lower and demonstrated little seasonal variability.
      The findings of this study show that PM2.5 is decreasing more sharply than PM2.5
      10 over time. This suggests the increasing importance of PM2.5-10 and traffic
      related sources for PM exposure and future policies. IMPLICATIONS: Although many
      studies have examined fine and coarse particle composition and sources, few
      studies have used concurrent measurements of these two fractions. Our analysis
      suggests that fine and coarse particles exhibit distinct compositions and
      sources. With better knowledge of the compositional and source differences
      between these two PM fractions, better decisions can be made about PM
      regulations. Further, such information is valuable in enabling epidemiologists to
      understand the ensuing health implications of PM exposure.

PMID- 25947126
TI  - Waste electrical and electronic equipment (WEEE) estimation: A case study of
      Ahvaz City, Iran.
AB  - The development of new technologies and the increasing consumption of electronic
      and electrical equipment have led to increased generation of e-waste in the
      municipal waste streams. This waste due to the presence of hazardous substances
      in its composition needs specific attention and management. The present study was
      carried out in Ahvaz metropolis using a survey method in 2011. For estimating the
      amount of waste electrical and electronic equipment (WEEE) generated, the "use
      and consumption" method was used. In order to determine the amounts of the
      electrical and electronic equipment that were used and their lifetime, and for
      investigating the current status of e-waste management in Ahvaz, an appropriate
      questionnaire was devised. In 2011, the total number of discarded electronic
      items was 2,157,742 units. According to the average weight of the equipment, the
      total generation of e-waste was 9952.25 metric tons per year and was 9.95 kg per
      capita per year. The highest e-waste generated was related to air conditioners,
      with 3125.36 metric tons per year, followed by the wastes from refrigerators and
      freezers, washing machines, and televisions. The wastes from desktop computers
      and laptops were 418 and 63 metric tons/year, respectively, and the corresponding
      values per capita were 0.42 and 0.063 kg, respectively. These results also showed
      that 10 tons fixed phones, 25 tons mobile phones, and by considering an average
      lifetime of 3 years for each lamp about 320 tons lamps were generated as e-waste
      in Ahvaz in the year 2011. Based on this study, currently there is not an
      integrated system for proper management of WEEE in Ahvaz, and this waste stream
      is collected and disposed of with other municipal waste. Some measures, including
      a specific collection system, recycling of valuable substances, and proper
      treatment and disposal, should be done about such waste. IMPLICATIONS: Ahvaz is
      one of the most important economic centers of Iran, and to the best of our
      knowledge, no study has been carried out to estimate the generation of waste
      electrical and electronic equipment (WEEE) in this city. Therefore, the authors
      estimated the generation of the WEEE by the "use and consumption" method. The
      results of this study can be useful not only for decision-making organizations of
      Ahvaz to manage and recycle this type of waste but also can be used as a method
      to estimate the generation of e-waste in different locations of the world,
      especially in places where the generation of such waste could be a risk to human
      health and the environment.

PMID- 25947127
TI  - In-use activity, fuel use, and emissions of heavy-duty diesel roll-off refuse
      trucks.
AB  - The objectives of this study were to quantify real-world activity, fuel use, and
      emissions for heavy duty diesel roll-off refuse trucks; evaluate the contribution
      of duty cycles and emissions controls to variability in cycle average fuel use
      and emission rates; quantify the effect of vehicle weight on fuel use and
      emission rates; and compare empirical cycle average emission rates with the U.S.
      Environmental Protection Agency's MOVES emission factor model predictions.
      Measurements were made at 1 Hz on six trucks of model years 2005 to 2012, using
      onboard systems. The trucks traveled 870 miles, had an average speed of 16 mph,
      and collected 165 tons of trash. The average fuel economy was 4.4 mpg, which is
      approximately twice previously reported values for residential trash collection
      trucks. On average, 50% of time is spent idling and about 58% of emissions occur
      in urban areas. Newer trucks with selective catalytic reduction and diesel
      particulate filter had NOx and PM cycle average emission rates that were 80%
      lower and 95% lower, respectively, compared to older trucks without. On average,
      the combined can and trash weight was about 55% of chassis weight. The marginal
      effect of vehicle weight on fuel use and emissions is highest at low loads and
      decreases as load increases. Among 36 cycle average rates (6 trucks*6 cycles),
      MOVES-predicted values and estimates based on real-world data have similar
      relative trends. MOVES-predicted CO2 emissions are similar to those of the real
      world, while NOx and PM emissions are, on average, 43% lower and 300% higher,
      respectively. The real-world data presented here can be used to estimate benefits
      of replacing old trucks with new trucks. Further, the data can be used to improve
      emission inventories and model predictions. IMPLICATIONS: In-use measurements of
      the real-world activity, fuel use, and emissions of heavy-duty diesel roll-off
      refuse trucks can be used to improve the accuracy of predictive models, such as
      MOVES, and emissions inventories. Further, the activity data from this study can
      be used to generate more representative duty cycles for more accurate chassis
      dynamometer testing. Comparisons of old and new model year diesel trucks are
      useful in analyzing the effect of fleet turnover. The analysis of effect of haul
      weight on fuel use can be used by fleet managers to optimize operations to reduce
      fuel cost.

PMID- 25947128
TI  - Emissions reduction policies and recent trends in Southern California's ambient
      air quality.
AB  - To assess accountability and effectiveness of air regulatory policies, we
      reviewed more than 20 years of monitoring data, emissions estimates, and
      regulatory policies across several southern California communities participating
      in a long-term study of children's health. Between 1994 and 2011, air quality
      improved for NO2 and PM2.5 in virtually all the monitored communities. Average
      NO2 declined 28% to 53%, and PM2.5 decreased 13% to 54%. Year-to-year PM2.5
      variability at lower pollution sites was large compared to changes in long-term
      trends. PM10 and O3 decreases were largest in communities that were initially
      among the most polluted. Trends in annual average NO2, PM2.5, and PM10
      concentrations in higher pollution communities were generally consistent with
      NOx, ROG, SOx, PM2.5, and PM10 emissions decreases. Reductions observed at one of
      the higher PM2.5 sites, Mira Loma, were generally within the range expected from
      reductions observed in ROG, NOx, SOx, and PM2.5 emissions. Despite a 38% increase
      in regional motor vehicle activity, vigorous economic growth, and a 30%
      population increase, total estimated emissions of NOx, ROG, SOx, PM2.5, and PM10
      decreased by 54%, 65%, 40%, 21%, and 15%, respectively, during the 20-year time
      period. Emission control strategies in California have achieved dramatic
      reductions in ambient NO2, O3, PM2.5, and PM10. However, additional reductions
      will still be needed to achieve current health-based clean air standards.
      IMPLICATIONS: For many cities facing the challenge of reducing air pollution to
      meet health-based standards, the emission control policies and pollution
      reduction programs adopted in southern California should serve as an example of
      the potential success of aggressive, comprehensive, and integrated approaches.
      Policies targeting on-road mobile emissions were the single most important
      element for observed improvements in the Los Angeles region. However, overall
      program success was the result of a much broader approach designed to achieve
      emission reductions across all major pollutants and emissions categories.

PMID- 25947129
TI  - Development of methodologies for identification and quantification of hazardous
      air pollutants from turbine engine emissions.
AB  - Aircraft turbine engines are a significant source of particulate matter (PM) and
      gaseous emissions in the vicinity of airports and military installations.
      Hazardous air pollutants (HAPs) (e.g., formaldehyde, benzene, naphthalene and
      other compounds) associated with aircraft emissions are an environmental concern
      both in flight and at ground level. Therefore, effective sampling,
      identification, and accurate measurement of these trace species are important to
      assess their environmental impact. This effort evaluates two established ambient
      air sampling and analysis methods, U.S. Environmental Protection Agency (EPA)
      Method TO-11A and National Institute for Occupational Safety and Health (NIOSH)
      Method 1501, for potential use to quantify HAPs from aircraft turbine engines.
      The techniques were used to perform analysis of the exhaust from a T63 turboshaft
      engine, and were examined using certified gas standards transferred through the
      heated sampling systems used for engine exhaust gaseous emissions measurements.
      Test results show that the EPA Method TO-11A (for aldehydes) and NIOSH Method
      1501 (for semivolatile hydrocarbons) were effective techniques for the sampling
      and analysis of most HAPs of interest. Both methods showed reasonable extraction
      efficiencies of HAP species from the sorbent tubes, with the exception of
      acrolein, styrene, and phenol, which were not well quantified. Formaldehyde
      measurements using dinitrophenylhydrazine (DNPH) tubes (EPA method TO-11A) were
      accurate for gas-phase standards, and compared favorably to measurements using
      gas-phase Fourier-transform infrared (FTIR) spectroscopy. In general, these two
      standard methodologies proved to be suitable techniques for field measurement of
      turbine engine HAPs within a reasonable (5-10 minutes) sampling period. Details
      of the tests, the analysis methods, calibration procedures, and results from the
      gas standards and T63 engine tested using a conventional JP-8 jet fuel are
      provided. IMPLICATIONS: HAPs from aviation-related sources are important because
      of their adverse health and environmental impacts in and around airports and
      flight lines. Simpler, more convenient techniques to measure the important HAPs,
      especially aldehydes and volatile organic HAPs, are needed to provide information
      about their occurrence and assist in the development of engines that emit fewer
      harmful emissions.

PMID- 25947130
TI  - Recent trends in gas-phase ammonia and PM2.5 ammonium in the Southeast United
      States.
AB  - Ammonia measurements from the Southeastern Aerosol Research and Characterization
      (SEARCH) study network were analyzed for trends over 9 yr (2004-2012) of
      observations. Total ammonia concentrations, defined as the sum of gas-phase
      ammonia and fine particle ammonium, were found to be decreasing by 1-4% yr(-1)
      and were qualitatively consistent with ammonia emission estimates for the SEARCH
      states of Alabama, Georgia, Mississippi, and Florida. On the other hand, gas
      phase ammonia mixing ratios were found to be slightly rising or steady over the
      region, leading to the observation that the gas-phase fraction of total ammonia
      has steadily increased over 2004-2012 as a result of declining emissions of the
      strong acid precursor species sulfur dioxide (SO2) and nitrogen oxides (NOx) and
      consequent reduced partitioning of ammonia to the fine particle phase. Because
      gas-phase ammonia is removed from the atmosphere more rapidly than fine particle
      ammonium, an increase in the gas-phase fraction of total ammonia may result in
      shifted deposition patterns as more ammonia is deposited closer to sources rather
      than transported downwind in fine particles. Additional long-term measurements
      and modeling studies are needed to determine if similar transitions of total
      ammonia to the gas phase are occurring outside of the Southeast and to assess if
      these changes are impacting plants and ecosystems near major ammonia sources.
      Unusually high ammonia concentrations observed in 2007 in the SEARCH measurements
      are hypothesized to be linked to emissions from wildfires that were much more
      prevalent across the Southeast during that year due to elevated temperatures and
      widespread drought. Although wildfires are currently estimated to be a relatively
      small fraction (3-10%) of total ammonia emissions in the Southeast, the projected
      increased incidence of wildfires in this region as a result of global climate
      change may lead to this source's increased importance over the rest of the 21st
      century. IMPLICATIONS: Ammonia concentrations from the Southeastern Aerosol
      Research and Characterization study (SEARCH) network are analyzed over the 9-yr
      period 2004-2012. Total ammonia (gaseous ammonia+PM2.5 ammonium) concentrations
      declined at a rate of 1-4% yr(-1), consistent with U.S. Environmental Protection
      Agency (EPA) emission estimates for the Southeast United States, but the fraction
      of ammonia in the gas phase has risen steadily (+1-3% yr(-1)) over the time
      period. Declining emissions of SO2 and NOx resulting from imposed air quality
      regulations have resulted in decreased atmospheric strong acids and less ammonia
      partitioning to the particle phase, which may impact the amount and overall
      pattern of ammonia deposition.

PMID- 25947131
TI  - Derivation of exemption formulas for air quality regulatory applications.
AB  - The regulatory agencies and the industries have the responsibility for assessing
      the environmental impact from the release of air pollutants, and for protecting
      environment and public health. The simple exemption formula is often used as a
      criterion for the purpose of screening air pollutants. That is, the exemption
      formula is used for air quality review and to determine whether a facility
      applying for and described in a new, modified, or revised air quality plan is
      exempted from further air quality review. The Bureau of Ocean Energy Management's
      (BOEM) air quality regulations are used to regulate air emissions and air
      pollutants released from the oil and gas facilities in the Gulf of Mexico. If a
      facility is not exempt after completing the air quality review, a refined air
      quality modeling will be required to regulate the air pollutants. However, at
      present, the scientific basis for BOEM's exemption formula is not available to
      the author. Therefore, the purpose of this paper is to provide the theoretical
      framework and justification for the use of BOEM's exemption formula. In this
      paper, several exemption formulas have been derived from the Gaussian and non
      Gaussian dispersion models; the Gaussian dispersion model is a special case of
      non-Gaussian dispersion model. The dispersion parameters obtained from the tracer
      experiments in the Gulf of Mexico are used in the dispersion models. In this
      paper, the dispersion parameters used in the dispersion models are also derived
      from the Monin-Obukhov similarity theory. In particular, it has been shown that
      the total amount of emissions from the facility for each air pollutant calculated
      using BOEM's exemption formula is conservative. IMPLICATIONS: The operation of
      offshore oil and gas facilities under BOEM's jurisdiction is required to comply
      with the BOEM's regulations. BOEM's air quality regulations are used to regulate
      air emissions and air pollutants released from the oil and gas facilities in the
      Gulf of Mexico. The exemption formulas have been used by BOEM and other
      regulatory agencies as a screening tool to regulate air emissions emitted from
      the oil and gas and other industries. Because of the BOEM's regulatory
      responsibility, it is important to establish the scientific basis and provide the
      justification for the exemption formulas. The methodology developed here could
      also be adopted and used by other regulatory agencies.

PMID- 25947132
TI  - Iron-functionalized titanium dioxide on flexible glass fibers for photocatalysis
      of benzene, toluene, ethylbenzene, and o-xylene (BTEX) under visible- or
      ultraviolet-light irradiation.
AB  - Iron-functionalized titanium dioxide (TiO2) composites with various Fe-to-Ti
      ratios were prepared on flexible glass fibers (GF-Fe-TiO2) via a sol-gel method,
      followed by a dip-coating process. The photocatalytic ability of these composites
      in degrading selected volatile organic compounds (VOCs; benzene, toluene,
      ethylbenzene, and o-xylene [BTEX]) at indoor concentration levels was examined.
      The GF-Fe-TiO2 composites were characterized using scanning electron microscopy,
      energy-dispersive X-ray elemental analysis, ultraviolet (UV)-visible
      spectroscopy, and X-ray diffraction. The GF-Fe-TiO2 composites showed superior
      photocatalytic performance to that of a reference glass fiber-supported TiO2
      photocatalyst for the treatment of BTEX under visible light. However, this trend
      was reversed under UV irradiation. Specifically, the average BTEX photocatalytic
      efficiencies of the 0.01-GF-Fe-TiO2 composite in a 3-hr visible-light
      photocatalytic process were 4%, 33%, 51%, and 74%, respectively. Conversely, the
      average BTEX photocatalytic efficiencies obtained for GF-TiO2 were close to 0%,
      5%, 16%, and 29%, respectively. These findings demonstrated that the GF-Fe-TiO2
      composites could be applied to photocatalytically purify BTEX, especially under
      visible-light exposure. Moreover, the GF-Fe-TiO2 composites prepared with
      different Fe-to-Ti ratios displayed different BTEX photocatalytic decomposition
      efficiencies under visible or UV light, allowing for optimization of the Fe-to-Ti
      ratio (which was found to be 0.01). IMPLICATIONS: The application of
      nanomaterials for air purification necessitates a supporting material to
      stabilize them while in contact with the treated air in the photocatalytic
      chamber. Glass fibers have an obvious advantage over other supporting materials
      mainly because of its flexibility, which makes it much easier to handle. However,
      the applications of glass fiber-supported, visible light-activated photocatalysts
      to the treatment of air pollutants are rarely reported in literature.
      Accordingly, this study aimed to investigate the applicability of glass fiber
      supported Fe-TiO2 for the purification of VOCs under visible- as well as UV-light
      exposure.

PMID- 25947133
TI  - Family Recovery.
AB  - This paper describes the recovery process of families of people with severe
      mental illnesses. The paper describes the phases of family recovery and useful
      interventions by phase with the family by professionals. The recovery process of
      people with serious mental illnesses has been well documented but that of the
      family has been neglected. Hopefully, this paper will generate further research
      into the impact of serious mental illnesses on family members. 

PMID- 25947134
TI  - Proliferation-dependent positioning of individual centromeres in the interphase
      nucleus of human lymphoblastoid cell lines.
AB  - The cell nucleus is a highly organized structure and plays an important role in
      gene regulation. Understanding the mechanisms that sustain this organization is
      therefore essential for understanding genome function. Centromeric regions (CRs)
      of chromosomes have been known for years to adopt specific nuclear positioning
      patterns, but the significance of this observation is not yet completely
      understood. Here, using a combination of fluorescence in situ hybridization and
      immunochemistry on fixed human cells and high-throughput imaging, we directly and
      quantitatively investigated the nuclear positioning of specific human CRs. We
      observe differential attraction of individual CRs toward both the nuclear border
      and the nucleoli, the former being enhanced in nonproliferating cells and the
      latter being enhanced in proliferating cells. Similar positioning patterns are
      observed in two different lymphoblastoid cell lines. Moreover, the positioning of
      CRs differs from that of noncentromeric regions, and CRs display specific
      orientations within chromosome territories. These results suggest the existence
      of not-yet-characterized mechanisms that drive the nuclear positioning of CRs and
      therefore pave the way toward a better understanding of how CRs affect nuclear
      organization. 

PMID- 25947135
TI  - MgcRacGAP restricts active RhoA at the cytokinetic furrow and both RhoA and Rac1
      at cell-cell junctions in epithelial cells.
AB  - Localized activation of Rho GTPases is essential for multiple cellular functions,
      including cytokinesis and formation and maintenance of cell-cell junctions.
      Although MgcRacGAP (Mgc) is required for spatially confined RhoA-GTP at the
      equatorial cortex of dividing cells, both the target specificity of Mgc's GAP
      activity and the involvement of phosphorylation of Mgc at Ser-386 are
      controversial. In addition, Mgc's function at cell-cell junctions remains
      unclear. Here, using gastrula-stage Xenopus laevis embryos as a model system, we
      examine Mgc's role in regulating localized RhoA-GTP and Rac1-GTP in the intact
      vertebrate epithelium. We show that Mgc's GAP activity spatially restricts
      accumulation of both RhoA-GTP and Rac1-GTP in epithelial cells--RhoA at the
      cleavage furrow and RhoA and Rac1 at cell-cell junctions. Phosphorylation at Ser
      386 does not switch the specificity of Mgc's GAP activity and is not required for
      successful cytokinesis. Furthermore, Mgc regulates adherens junction but not
      tight junction structure, and the ability to regulate adherens junctions is
      dependent on GAP activity and signaling via the RhoA pathway. Together these
      results indicate that Mgc's GAP activity down-regulates the active populations of
      RhoA and Rac1 at localized regions of epithelial cells and is necessary for
      successful cytokinesis and cell-cell junction structure.

PMID- 25947136
TI  - Tumor suppressor protein Lgl mediates G1 cell cycle arrest at high cell density
      by forming an Lgl-VprBP-DDB1 complex.
AB  - Lethal giant larvae (Lgl) is an evolutionarily conserved tumor suppressor whose
      loss of function causes disrupted epithelial architecture with enhanced cell
      proliferation and defects in cell polarity. A role for Lgl in the establishment
      and maintenance of cell polarity via suppression of the PAR-aPKC polarity complex
      is established; however, the mechanism by which Lgl regulates cell proliferation
      is not fully understood. Here we show that depletion of Lgl1 and Lgl2 in MDCK
      epithelial cells results in overproliferation and overproduction of Lgl2 causes
      G1 arrest. We also show that Lgl associates with the VprBP-DDB1 complex
      independently of the PAR-aPKC complex and prevents the VprBP-DDB1 subunits from
      binding to Cul4A, a central component of the CRL4 [VprBP] ubiquitin E3 ligase
      complex implicated in G1- to S-phase progression. Consistently, depletion of
      VprBP or Cul4 rescues the overproliferation of Lgl-depleted cells. In addition,
      the affinity between Lgl2 and the VprBP-DDB1 complex increases at high cell
      density. Further, aPKC-mediated phosphorylation of Lgl2 negatively regulates the
      interaction between Lgl2 and VprBP-DDB1 complex. These results suggest a
      mechanism protecting overproliferation of epithelial cells in which Lgl plays a
      critical role by inhibiting formation of the CRL4 [VprBP] complex, resulting in
      G1 arrest. 

PMID- 25947137
TI  - A quantitative imaging-based screen reveals the exocyst as a network hub
      connecting endocytosis and exocytosis.
AB  - The coupling of endocytosis and exocytosis underlies fundamental biological
      processes ranging from fertilization to neuronal activity and cellular polarity.
      However, the mechanisms governing the spatial organization of endocytosis and
      exocytosis require clarification. Using a quantitative imaging-based screen in
      budding yeast, we identified 89 mutants displaying defects in the localization of
      either one or both pathways. High-resolution single-vesicle tracking revealed
      that the endocytic and exocytic mutants she4? and bud6? alter post-Golgi vesicle
      dynamics in opposite ways. The endocytic and exocytic pathways display strong
      interdependence during polarity establishment while being more independent during
      polarity maintenance. Systems analysis identified the exocyst complex as a key
      network hub, rich in genetic interactions with endocytic and exocytic components.
      Exocyst mutants displayed altered endocytic and post-Golgi vesicle dynamics and
      interspersed endocytic and exocytic domains compared with control cells. These
      data are consistent with an important role for the exocyst in coordinating
      endocytosis and exocytosis. 

PMID- 25947139
TI  - Determining clinical and biological indicators for health outcomes in adult
      patients with childhood onset of congenital adrenal hyperplasia.
AB  - AIM: Adverse outcomes in adult congenital adrenal hyperplasia (CAH) patients are
      frequent. The determinants of them have not yet been established. OBJECTIVE: To
      establish the prevalence of adverse outcomes and to find determining factors for
      each of them. DESIGN, PATIENTS, AND METHODS: Cross-sectional monocentric study of
      104 patients with childhood onset of CAH (71 women, 33 men). Analysis established
      first the determinants of clinical, hormonal, genetic variables and second a
      composite criterion for some of the outcomes and determinants. RESULTS: BMI was
      above 25 kg/m(2) in 44% of the cohort, adrenal hyperplasia and/or nodules were
      present in 45% of the patients, and irregular menstrual cycles and
      hyperandrogenism were found in 50 and 35% of the women respectively. In
      univariate analysis, the determinants of these outcomes were all linked to
      disease control, especially 17-hydroxyprogesterone (17OHP) and androstenedione
      concentrations. Low weight was a determinant of abnormal bone mineral density
      (BMD) (60% of the cohort). Multivariate analysis confirmed these data. A classic
      form (CF) of CAH was a determinant of testicular adrenal rest tumors (TARTs) (36%
      of the men). Total cumulative glucocorticoid dose was a determinant of BMI and
      TART, whereas fludrocortisone dose was a determinant of TART (P=0.03). In men,
      the composite criterion was associated with androstenedione concentration and CF.
      In women, the composite criterion was associated with total testosterone
      concentration. CONCLUSION: The present study confirms the high prevalence of
      adverse outcomes in CAH patients. These are, most often, related to disease
      control. The impaired health status of adults with CAH could therefore be
      improved through the modification of treatment.

PMID- 25947140
TI  - Imaging in endocrinology: 2-[18F]-fluoro-2-deoxy-D-glucose positron emission
      tomography/computed tomography in differentiated thyroid carcinoma: clinical
      indications and controversies in diagnosis and follow-up.
AB  - In recent years, 2-[(18)F]-fluoro-2-deoxy-D-glucose positron emission
      tomography/computed tomography (FDG-PET/CT) has emerged as an important tool for
      the postoperative management of patients with differentiated thyroid cancer (DTC)
      and it is widely used in selected clinical situations. The most valuable role
      that FDG-PET/CT plays in clinical practice is that it can be used to obtain
      prognostic information in patients with increasing thyroglobulin (Tg) levels and
      negative (131)I whole-body scan post-thyroidectomy and radioiodine (RAI)
      ablation. FDG-PET/CT may also have a potential role in the initial staging and
      follow-up of high-risk patients with aggressive histological subtypes, in the
      identification of patients who are at the highest risk of disease-specific
      mortality, in the management of patients with RAI-refractory disease, in clinical
      trials of novel targeted therapies in patients with advanced metastatic disease,
      and in the evaluation of thyroid nodules with indeterminate fine-needle
      aspiration for cytology. However, several controversies remain to be resolved,
      namely: the cutoff value of Tg in the selection of DTC patients for FDG-PET/CT,
      whether FDG-PET/CT scanning should be performed under thyrotropin stimulation or
      suppression, and the clinical significance of thyroid FDG-PET/CT incidentalomas.
      The aim of the present article is to provide an overview of the data about the
      molecular basis for, clinical indications of, and controversies related to the
      use of FDG-PET/CT in patients with DTC.

PMID- 25947138
TI  - Synergistic interaction between the fibroblast growth factor and bone
      morphogenetic protein signaling pathways in lens cells.
AB  - Fibroblast growth factors (FGFs) play a central role in two processes essential
      for lens transparency--fiber cell differentiation and gap junction-mediated
      intercellular communication (GJIC). Using serum-free primary cultures of chick
      lens epithelial cells (DCDMLs), we investigated how the FGF and bone
      morphogenetic protein (BMP) signaling pathways positively cooperate to regulate
      lens development and function. We found that culturing DCDMLs for 6 d with the
      BMP blocker noggin inhibits the canonical FGF-to-ERK pathway upstream of FRS2
      activation and also prevents FGF from stimulating FRS2- and ERK-independent gene
      expression, indicating that BMP signaling is required at the level of FGF
      receptors. Other experiments revealed a second type of BMP/FGF interaction by
      which FGF promotes expression of BMP target genes as well as of BMP4. Together
      these studies reveal a novel mode of cooperation between the FGF and BMP pathways
      in which BMP keeps lens cells in an optimally FGF-responsive state and,
      reciprocally, FGF enhances BMP-mediated gene expression. This interaction
      provides a mechanistic explanation for why disruption of either FGF or BMP
      signaling in the lens leads to defects in lens development and function.

PMID- 25947141
TI  - Changes in circulating IGF1 receptor stimulating activity do not parallel changes
      in total IGF1 during GH treatment of GH-deficient adults.
AB  - CONTEXT: Previously we demonstrated that IGF1 receptor stimulating activity
      (IGF1RSA) offers advantages in diagnostic evaluation of adult GH deficiency
      (GHD). It is unknown whether IGF1RSA can be used to monitor GH therapy.
      OBJECTIVE: To investigate the value of circulating IGF1RSA for monitoring GH
      therapy. DESIGN/METHODS: 106 patients (54 m; 52 f) diagnosed with GHD were
      included; 22 were GH-naive, 84 were already on GH treatment and discontinued
      therapy 4 weeks before baseline values were established. IGF1RSA was determined
      by the IGF1R kinase receptor activating assay, total IGF1 by immunoassay
      (Immulite). GH doses were titrated to achieve total IGF1 levels within the normal
      range. RESULTS: After 12 months, total IGF1 and IGF1RSA increased significantly
      (total IGF1 from 8.1 (95% CI 7.3-8.9) to 14.9 (95% CI 13.5-16.4) nmol/l and
      IGF1RSA from 115 (95% CI 104-127) to 181 (95% CI 162-202) pmol/l). After 12
      months, total IGF1 normalized in 81% of patients, IGF1RSA in 51% and remained
      below normal in more than 40% of patients in whom total IGF1 had normalized.
      CONCLUSIONS: During 12 months of GH treatment, changes in IGF1RSA did not
      parallel changes in total IGF1. Despite normalization of total IGF1, IGF1RSA
      remained subnormal in a considerable proportion of patients. At present our
      results have no short-term consequences for GH therapy of GHD patients. However,
      based on our findings we propose future studies to examine whether titrating GH
      dose against IGF1RSA results in a better clinical outcome than titrating against
      total IGF1.

PMID- 25947143
TI  - Self-reported endocrine late effects in adults treated for brain tumours, Hodgkin
      and non-Hodgkin lymphoma: a registry based study in Northern Germany.
AB  - OBJECTIVE: Due to the increasing success and survival rates in the primary
      treatment of malignancies derived from the CNS as well as the hematopoietic
      system, endocrine late effects of cancer and its therapy are of growing
      importance. Despite evaluation of these late effects in patients treated for
      cancer in childhood, the impact on adults remains largely unclear. METHODS: 1035
      adult patients primarily diagnosed with a CNS malignancy, a Hodgkin (HL) or non
      Hodgkin lymphoma (NHL) between 1998 and 2008 were recruited via the regional
      epidemiological cancer registry covering ~ 2.8 million inhabitants in the federal
      state of Schleswig-Holstein, Northern Germany. The prevalence of endocrine
      disorders and current psychosocial impairment was assessed employing several
      questionnaires (SF-36v1, WHO-5). RESULTS: Fully completed questionnaires of 558
      patients were available for subsequent analysis showing markedly reduced overall
      performance and psychological status when compared to German reference data.
      Thyroid disorders were reported in 16.3% of patients with 10.4% suffering from
      hypo- and 5.9% from hyperthyroidism. Overall, 17.6% stated to be affected by
      diabetes mellitus with an increased rate of 21.1% among NHL patients and 11.5% of
      participants were affected by osteoporosis. CONCLUSION: Compared to German
      population based studies on the prevalence of diabetes mellitus, osteoporosis and
      thyroid disorders the frequency of all these endocrine problems was significantly
      increased in CNS, HL, and NHL cancer survivors. These data confirm that not only
      children and adolescents but also adult cancer patients are at risk for therapy
      associated endocrine late effects.

PMID- 25947142
TI  - Circulating IGF1 and IGFBP3 in relation to the development of beta-cell
      autoimmunity in young children.
AB  - OBJECTIVE: This study aimed at investigating the role of IGF1 and IGF binding
      protein 3 (IGFBP3) in the development of beta-cell autoimmunity. METHODS: Five
      hundred and sixty-three subjects with HLA-conferred susceptibility to type 1
      diabetes (T1D) were monitored for signs of seroconversion to positivity for
      insulin and/or GAD, IA2, and zinc transporter 8 autoantibodies by the age of 3
      years. In 40 subjects who developed at least one autoantibody, IGF1 and IGFBP3
      plasma concentrations were measured and compared with 80 control subjects who
      remained negative for autoantibodies, and were matched for age, sex, country of
      origin, and HLA genotype. The increments of IGF1, IGFBP3, and IGF1/IGFBP3 molar
      ratio before and after seroconverison were compared with corresponding time
      intervals in controls. RESULTS: The IGF1 concentrations at the age of 12 months
      and the IGF1/IGFBP3 ratio at the age of 24 months were lower in the autoantibody
      positive children (P<0.05). The increase in circulating IGFBP3 was significantly
      higher in the autoantibody-positive children before seroconversion than in the
      corresponding time intervals in controls (0.43 mg/l; 95% CI 0.29-0.56 vs 0.22
      mg/l; 95% CI 0.10-0.34 mg/l; P<0.01). Children carrying the high-risk HLA
      genotype had lower plasma IGF1 and IGFBP3 concentrations at the age of 24 months
      than those with low-risk genotypes (P<0.05 and < 0.01 respectively). CONCLUSIONS:
      Circulating IGF1 and IGFBP3 appear to have a role in early development of beta
      cell autoimmunity. The decreased IGF1 concentrations in children with the high
      risk HLA genotype may contribute to the reduced growth previously described in
      such children.

PMID- 25947144
TI  - Characteristics of the Vdelta2 CDR3 Sequence of Peripheral gammadelta T Cells in
      Patients with Pulmonary Tuberculosis and Identification of a New Tuberculosis
      Related Antigen Peptide.
AB  - Antigen-specific gammadelta T cells may play an important role in the immune
      response to Mycobacterium tuberculosis. However, little is known about the
      characteristics of the length distribution of the delta2-chain complementarity
      determining region 3 (delta2 CDR3) of the gammadelta T-cell receptor (TCR) in
      patients with active pulmonary tuberculosis (TB) on a large scale. In addition,
      M. tuberculosis-activated gammadelta T cells potentially inhibit intracellular
      mycobacterial growth, but phosphoantigen-activated gammadelta T cells do not.
      Only a few M. tuberculosis-related antigen peptides or proteins that are
      recognized by gammadelta TCR have been identified. Twenty-four healthy donors
      (HDs) and 27 TB patients were included in the present study. The gene-scanning
      technique found that the delta2 CDR3 length distribution patterns of gammadelta
      TCR in TB patients were perturbed, and each pattern included different
      predominant CDR3 sequences. The predominant delta2 CDR3 sequences of gammadelta
      TCRs, which originated from TB patients and HD gammadelta T cells that were
      stimulated by M. tuberculosis heat resistance antigen (Mtb-HAg), were used as
      probes to screen peptides recognized by gammadelta TCR using a phage display
      library. We identified four peptides that bound to the predominant delta2 CDR3
      fragments and showed homology to M. tuberculosis genes in a BLAST search.
      Notably, one peptide was related to M. tuberculosis H37Rv (QHIPKPP), and this
      fragment was confirmed as a ligand for the gammadelta TCR. Two fragments, Ag1 and
      Ag2, activated gammadelta T cells from HD or TB patients. In summary, the delta2
      CDR3 lineage of TB patients apparently drifts, and the predominant delta2 CDR3
      sequence that recognizes M. tuberculosis may exhibit specificity. The identified
      M. tuberculosis-related antigen peptides may be used as vaccines or adjuvants for
      protective immunity against M. tuberculosis. 

PMID- 25947145
TI  - Mycobacterium bovis BCG Vaccination Induces Divergent Proinflammatory or
      Regulatory T Cell Responses in Adults.
AB  - Mycobacterium bovis bacillus Calmette-Guerin (BCG), the only currently available
      vaccine against tuberculosis, induces variable protection in adults. Immune
      correlates of protection are lacking, and analyses on cytokine-producing T cell
      subsets in protected versus unprotected cohorts have yielded inconsistent
      results. We studied the primary T cell response, both proinflammatory and
      regulatory T cell responses, induced by BCG vaccination in adults. Twelve healthy
      adult volunteers who were tuberculin skin test (TST) negative, QuantiFERON test
      (QFT) negative, and BCG naive were vaccinated with BCG and followed up
      prospectively. BCG vaccination induced an unexpectedly dichotomous immune
      response in this small, BCG-naive, young-adult cohort: BCG vaccination induced
      either gamma interferon-positive (IFN-gamma(+)) interleukin 2-positive (IL-2(+))
      tumor necrosis factor alpha-positive (TNF-alpha(+)) polyfunctional CD4(+) T cells
      concurrent with CD4(+) IL-17A(+) and CD8(+) IFN-gamma(+) T cells or, in contrast,
      virtually absent cytokine responses with induction of CD8(+) regulatory T cells.
      Significant induction of polyfunctional CD4(+) IFN-gamma(+) IL-2(+) TNF-alpha(+)
      T cells and IFN-gamma production by peripheral blood mononuclear cells (PBMCs)
      was confined to individuals with strong immunization-induced local skin
      inflammation and increased serum C-reactive protein (CRP). Conversely, in
      individuals with mild inflammation, regulatory-like CD8(+) T cells were uniquely
      induced. Thus, BCG vaccination either induced a broad proinflammatory T cell
      response with local inflammatory reactogenicity or, in contrast, a predominant
      CD8(+) regulatory T cell response with mild local inflammation, poor cytokine
      induction, and absent polyfunctional CD4(+) T cells. Further detailed fine
      mapping of the heterogeneous host response to BCG vaccination using classical and
      nonclassical immune markers will enhance our understanding of the mechanisms and
      determinants that underlie the induction of apparently opposite immune responses
      and how these impact the ability of BCG to induce protective immunity to TB. 

PMID- 25947146
TI  - Protection Provided by an Encapsulated Live Attenuated DeltaabcBA Strain of
      Brucella ovis against Experimental Challenge in a Murine Model.
AB  - This study aimed to evaluate the Brucella ovis DeltaabcBA strain as a vaccine
      candidate in the murine model. BALB/c mice were subcutaneously or
      intraperitoneally immunized with a single dose or three doses of the B. ovis
      DeltaabcBA strain and then were challenged with wild-type B. ovis. Single or
      multiple immunizations provided only mild protection, with significantly smaller
      numbers of wild-type B. ovis CFU in the livers of immunized mice but not in the
      spleens. Encapsulation of B. ovis DeltaabcBA significantly improved protection
      against experimental challenges in both BALB/c and C57BL/6 mice. Furthermore,
      immunization with encapsulated B. ovis DeltaabcBA markedly prevented lesions in
      the spleens and livers of experimentally challenged mice. These results
      demonstrated that the encapsulated B. ovis DeltaabcBA strain confers protection
      to mice; therefore, this strain has potential as a vaccine candidate for rams. 

PMID- 25947147
TI  - Cross-Reactivity, Epitope Spreading, and De Novo Immune Stimulation Are Possible
      Mechanisms of Cross-Protection of Nonvaccine Human Papillomavirus (HPV) Types in
      Recipients of HPV Therapeutic Vaccines.
AB  - Numerous versions of human papillomavirus (HPV) therapeutic vaccines designed to
      treat individuals with established HPV infection, including those with cervical
      intraepithelial neoplasia (CIN), are in development because approved prophylactic
      vaccines are not effective once HPV infection is established. As human
      papillomavirus 16 (HPV-16) is the most commonly detected type worldwide, all
      versions of HPV therapeutic vaccines contain HPV-16, and some also contain HPV
      18. While these two HPV types are responsible for approximately 70% of cervical
      cancer cases, there are other high-risk HPV types known to cause malignancy.
      Therefore, it would be of interest to assess whether these HPV therapeutic
      vaccines may confer cross-protection against other high-risk HPV types. Data
      available from a few clinical trials that enrolled subjects with CINs regardless
      of the HPV type(s) present demonstrated clinical responses, as measured by CIN
      regression, in subjects with both vaccine-matched and nonvaccine HPV types. The
      currently available evidence demonstrating cross-reactivity, epitope spreading,
      and de novo immune stimulation as possible mechanisms of cross-protection
      conferred by investigational HPV therapeutic vaccines is discussed. 

PMID- 25947148
TI  - Molecular Engineering of Ghfp, the Gonococcal Orthologue of Neisseria
      meningitidis Factor H Binding Protein.
AB  - Knowledge of the sequences and structures of proteins produced by microbial
      pathogens is continuously increasing. Besides offering the possibility of
      unraveling the mechanisms of pathogenesis at the molecular level, structural
      information provides new tools for vaccine development, such as the opportunity
      to improve viral and bacterial vaccine candidates by rational design. Structure
      based rational design of antigens can optimize the epitope repertoire in terms of
      accessibility, stability, and variability. In the present study, we used epitope
      mapping information on the well-characterized antigen of Neisseria meningitidis
      factor H binding protein (fHbp) to engineer its gonococcal homologue, Ghfp.
      Meningococcal fHbp is typically classified in three distinct antigenic variants.
      We introduced epitopes of fHbp variant 1 onto the surface of Ghfp, which is
      naturally able to protect against meningococcal strains expressing fHbp of
      variants 2 and 3. Heterologous epitopes were successfully transplanted, as
      engineered Ghfp induced functional antibodies against all three fHbp variants.
      These results confirm that structural vaccinology represents a successful
      strategy for modulating immune responses, and it is a powerful tool for
      investigating the extension and localization of immunodominant epitopes. 

PMID- 25947149
TI  - Danger signal-dependent activation of human dendritic cells by plasma-derived
      factor VIII products.
AB  - Treatment of haemophilia A by infusions of the clotting factor VIII (FVIII)
      results in the development of inhibitors/anti-drug antibodies in up to 25 % of
      patients. Mechanisms leading to immunogenicity of FVIII products are not yet
      fully understood. Amongst other factors, danger signals as elicited upon
      infection or surgery have been proposed to play a role. In the present study, we
      focused on effects of danger signals on maturation and activation of dendritic
      cells (DC) in the context of FVIII application. Human monocyte-derived DC were
      treated with FVIII alone, with a danger signal alone or a combination of both. By
      testing more than 60 different healthy donors, we show that FVIII and the
      bacterial danger signal lipopolysaccharide synergise in increasing DC activation,
      as characterised by increased expression of co-stimulatory molecules and
      secretion of pro-inflammatory cytokines. The degree and frequency of this
      synergistic activation correlate with CD86 expression levels on immature DC prior
      to stimulation. In our assay system, plasma-derived but not recombinant FVIII
      products activate human DC in a danger signal-dependent manner. Further tested
      danger signals, such as R848 also induced DC activation in combination with
      FVIII, albeit not in every tested donor. In our hands, human DC but not human B
      cells or macrophages could be activated by FVIII in a danger signal-dependent
      manner. Our results suggest that immunogenicity of FVIII is a result of multiple
      factors including the presence of danger, predisposition of the patient, and the
      choice of a FVIII product for treatment.

PMID- 25947150
TI  - Connectivity reveals relationship of brain areas for reward-guided learning and
      decision making in human and monkey frontal cortex.
AB  - Reward-guided decision-making depends on a network of brain regions. Among these
      are the orbitofrontal and the anterior cingulate cortex. However, it is difficult
      to ascertain if these areas constitute anatomical and functional unities, and how
      these areas correspond between monkeys and humans. To address these questions we
      looked at connectivity profiles of these areas using resting-state functional MRI
      in 38 humans and 25 macaque monkeys. We sought brain regions in the macaque that
      resembled 10 human areas identified with decision making and brain regions in the
      human that resembled six macaque areas identified with decision making. We also
      used diffusion-weighted MRI to delineate key human orbital and medial frontal
      brain regions. We identified 21 different regions, many of which could be linked
      to particular aspects of reward-guided learning, valuation, and decision making,
      and in many cases we identified areas in the macaque with similar coupling
      profiles. 

PMID- 25947152
TI  - Embracing general theory and taxon-level idiosyncrasies to explain nutrient
      recycling.

PMID- 25947151
TI  - Modulation of extrasynaptic NMDA receptors by synaptic and tonic zinc.
AB  - Many excitatory synapses contain high levels of mobile zinc within glutamatergic
      vesicles. Although synaptic zinc and glutamate are coreleased, it is
      controversial whether zinc diffuses away from the release site or whether it
      remains bound to presynaptic membranes or proteins after its release. To study
      zinc transmission and quantify zinc levels, we required a high-affinity rapid
      zinc chelator as well as an extracellular ratiometric fluorescent zinc sensor. We
      demonstrate that tricine, considered a preferred chelator for studying the role
      of synaptic zinc, is unable to efficiently prevent zinc from binding low
      nanomolar zinc-binding sites, such as the high-affinity zinc-binding site found
      in NMDA receptors (NMDARs). Here, we used ZX1, which has a 1 nM zinc dissociation
      constant and second-order rate constant for binding zinc that is 200-fold higher
      than those for tricine and CaEDTA. We find that synaptic zinc is phasically
      released during action potentials. In response to short trains of presynaptic
      stimulation, synaptic zinc diffuses beyond the synaptic cleft where it inhibits
      extrasynaptic NMDARs. During higher rates of presynaptic stimulation, released
      glutamate activates additional extrasynaptic NMDARs that are not reached by
      synaptically released zinc, but which are inhibited by ambient, tonic levels of
      nonsynaptic zinc. By performing a ratiometric evaluation of extracellular zinc
      levels in the dorsal cochlear nucleus, we determined the tonic zinc levels to be
      low nanomolar. These results demonstrate a physiological role for endogenous
      synaptic as well as tonic zinc in inhibiting extrasynaptic NMDARs and thereby
      fine tuning neuronal excitability and signaling. 

PMID- 25947153
TI  - The 3D structure of Kaposi sarcoma herpesvirus LANA C-terminal domain bound to
      DNA.
AB  - Kaposi sarcoma herpesvirus (KSHV) persists as a latent nuclear episome in
      dividing host cells. This episome is tethered to host chromatin to ensure proper
      segregation during mitosis. For duplication of the latent genome, the cellular
      replication machinery is recruited. Both of these functions rely on the
      constitutively expressed latency-associated nuclear antigen (LANA) of the virus.
      Here, we report the crystal structure of the KSHV LANA DNA-binding domain (DBD)
      in complex with its high-affinity viral target DNA, LANA binding site 1 (LBS1),
      at 2.9 A resolution. In contrast to homologous proteins such as Epstein-Barr
      virus nuclear antigen 1 (EBNA-1) of the related gamma-herpesvirus Epstein-Barr
      virus, specific DNA recognition by LANA is highly asymmetric. In addition to
      solving the crystal structure, we found that apart from the two known LANA
      binding sites, LBS1 and LBS2, LANA also binds to a novel site, denoted LBS3. All
      three sites are located in a region of the KSHV terminal repeat subunit
      previously recognized as a minimal replicator. Moreover, we show that the LANA
      DBD can coat DNA of arbitrary sequence by virtue of a characteristic lysine
      patch, which is absent in EBNA-1 of the Epstein-Barr virus. Likely, these higher
      order assemblies involve the self-association of LANA into supermolecular
      spirals. One such spiral assembly was solved as a crystal structure of 3.7 A
      resolution in the absence of DNA. On the basis of our data, we propose a model
      for the controlled nucleation of higher-order LANA oligomers that might
      contribute to the characteristic subnuclear KSHV microdomains ("LANA speckles"),
      a hallmark of KSHV latency. 

PMID- 25947154
TI  - Transcriptome diversity among rice root types during asymbiosis and interaction
      with arbuscular mycorrhizal fungi.
AB  - Root systems consist of different root types (RTs) with distinct developmental
      and functional characteristics. RTs may be individually reprogrammed in response
      to their microenvironment to maximize adaptive plasticity. Molecular
      understanding of such specific remodeling--although crucial for crop improvement-
      is limited. Here, RT-specific transcriptomes of adult rice crown, large and fine
      lateral roots were assessed, revealing molecular evidence for functional
      diversity among individual RTs. Of the three rice RTs, crown roots displayed a
      significant enrichment of transcripts associated with phytohormones and secondary
      cell wall (SCW) metabolism, whereas lateral RTs showed a greater accumulation of
      transcripts related to mineral transport. In nature, arbuscular mycorrhizal (AM)
      symbiosis represents the default state of most root systems and is known to
      modify root system architecture. Rice RTs become heterogeneously colonized by AM
      fungi, with large laterals preferentially entering into the association. However,
      RT-specific transcriptional responses to AM symbiosis were quantitatively most
      pronounced for crown roots despite their modest physical engagement in the
      interaction. Furthermore, colonized crown roots adopted an expression profile
      more related to mycorrhizal large lateral than to noncolonized crown roots,
      suggesting a fundamental reprogramming of crown root character. Among these
      changes, a significant reduction in SCW transcripts was observed that was
      correlated with an alteration of SCW composition as determined by mass
      spectrometry. The combined change in SCW, hormone- and transport-related
      transcript profiles across the RTs indicates a previously overlooked switch of
      functional relationships among RTs during AM symbiosis, with a potential impact
      on root system architecture and functioning.

PMID- 25947156
TI  - Corneal thickness, epithelial thickness and axial length differences in normal
      and high myopia.
AB  - BACKGROUND: Corneal biometric parameters can possibly be influenced by high
      myopia (HM). The influence of HM on corneal thickness (CT), epithelial thickness
      (ET) has not yet been clearly established. The aim of this study is to observe
      ET, CT and axial length (AL) differences between in normal and subjects with HMs
      and to investigate factors influencing the corneal biometric parameters and AL,
      such as age and gender. METHODS: A total of 97 normal subjects (97 eyes) and 48
      HM subjects (48 eyes) were included. The ET and CT of the central 6-mm diameter
      (17 regions) and the AL data were captured. The 17 corneal and epithelial regions
      were the center (1 mm radius, area a), the inner ring (2.5 mm radius, area b),
      the outer ring (3 mm radius, area c) and the 8 radial scan lines in eight
      directions (Superior (1) , SN (2), Nasal (3), IN (4), Inferior (5), IT (6),
      Temporal (7), ST (8)) with an angle of 45 degrees  between each consecutive scan
      line (a, b 1-8, c 1-8). RESULTS: The ALs were increased about 4 mm in the HMs (P
      < 0.001). No differences in ET were observed; in contrast, significantly thicker
      CTs were observed in the HMs in 16 regions except the b5 subregion. In normal
      group, age was negatively correlated with AL but not CCT and CET and gender was
      correlated with CET. In HM group, age was not correlated with CCT , AL or CET and
      gender was correlated with AL and CCT but not CET. CONCLUSIONS: CT was thicker in
      the HMs but not ET. Age and gender should be considered for AL, CT and ET in both
      normal and HM group.

PMID- 25947155
TI  - Regulation of the microtubular cytoskeleton by Polycystin-1 favors focal
      adhesions turnover to modulate cell adhesion and migration.
AB  - BACKGROUND: Polycystin-1 (PC-1) is a large plasma membrane receptor, encoded by
      the PKD1 gene, which is mutated in most cases of Autosomal Dominant Polycystic
      Kidney Disease (ADPKD). The disease is characterized by renal cysts. The precise
      function of PC-1 remains elusive, although several studies suggest that it can
      regulate the cellular shape in response to external stimuli. We and others
      reported that PC-1 regulates the actin cytoskeleton and cell migration. RESULTS:
      Here we show that cells over-expressing PC-1 display enhanced adhesion rates to
      the substrate, while cells lacking PC-1 have a reduced capability to adhere. In
      search for the mechanism responsible for this new property of PC-1 we found that
      this receptor is able to regulate the stability of the microtubules, in addition
      to its capability to regulate the actin cytoskeleton. The two cytoskeletal
      components are acting in a coordinated fashion. Notably, we uncovered that PC-1
      regulation of the microtubule cytoskeleton impacts on the turnover rates of focal
      adhesions in migrating cells and we link all these properties to the capability
      of PC-1 to regulate the activation state of Focal Adhesion Kinase (FAK).
      CONCLUSIONS: In this study we show several new features of the PC-1 receptor in
      modulating microtubules and adhesion dynamics, which are essential for its
      capability to regulate migration.

PMID- 25947157
TI  - Temporomandibular joint involvement in Juvenile Idiopathic Arthritis: reliability
      and validity of a screening protocol for the rheumatologist.
AB  - BACKGROUND: In Juvenile Idiopathic Arthritis (JIA) the temporomandibular joint
      (TMJ) can be involved leading to pain, dysfunction and growth disturbances of the
      mandible and associated structures. There may be value to a three minute
      screening protocol allowing the rheumatologist to detect TMJ involvement
      systematically. Reliability and validity of the TMJ protocol for detecting TMJ co
      morbidity were determined in 74 consecutive JIA patients. METHODS: The
      assessments of the rheumatologist and of a reference examiner (RE) were compared
      and validity of the TMJ protocol was established using the disease activity
      (JADAS-27) as an external reference. RESULTS: The internal consistency of the
      protocol was 0.73 (Cronbach's alpha). The inter-examiner agreement between the
      rheumatologist and the RE varied between 0.25 and 0.87 (Cohen's Kappa).
      Sensitivity and specificity, with the JADAS "3.8" indicating minimal disease
      activity, were 0.57 and 0.77 respectively. The area under the curve (AUC) was
      0.70. A cut-off value of two positive items was found to be an optimal threshold
      to select the patients with likely TMJ involvement. CONCLUSIONS: The use of the
      protocol is feasible in everyday clinical practice. Reliability and validity
      aspects were satisfactory. The screening protocol for TMJ involvement provides
      the rheumatologist with systematic and focused TMJ information which relates to
      the JIA disease activity (JADAS-27).

PMID- 25947158
TI  - Limited evidence for diagnosing and treating "non-criteria obstetric
      antiphospholipid syndrome".

PMID- 25947159
TI  - Immunology of protection from Ebola virus infection.
AB  - A December 2014 meeting reviewed Ebola virus immunology relevant to vaccine
      development, including Ebola prevention, immunity, assay standardization, and
      regulatory considerations. Vaccinated humans appear to achieve immune responses
      comparable in magnitude with those associated with protection in nonhuman
      primates, suggesting that immunological data could be used to demonstrate vaccine
      efficacy. 

PMID- 25947160
TI  - How to handle an industry in disruption: Intervene or laissez-faire?
AB  - An analysis of four regions in four countries suggests that the best way to
      mitigate disruption of the pharmaceutical industry is not to ignore or stem it
      but to sponsor initiatives that keep scientists engaged. 

PMID- 25947161
TI  - Dysregulation of astrocyte extracellular signaling in Costello syndrome.
AB  - Astrocytes produce an assortment of signals that promote neuronal maturation
      according to a precise developmental timeline. Is this orchestrated timing and
      signaling altered in human neurodevelopmental disorders? To address this
      question, the astroglial lineage was investigated in two model systems of a
      developmental disorder with intellectual disability caused by mutant Harvey rat
      sarcoma viral oncogene homolog (HRAS) termed Costello syndrome: mutant HRAS human
      induced pluripotent stem cells (iPSCs) and transgenic mice. Human iPSCs derived
      from patients with Costello syndrome differentiated to astroglia more rapidly in
      vitro than those derived from wild-type cell lines with normal HRAS, exhibited
      hyperplasia, and also generated an abundance of extracellular matrix remodeling
      factors and proteoglycans. Acute treatment with a farnesyl transferase inhibitor
      and knockdown of the transcription factor SNAI2 reduced expression of several
      proteoglycans in Costello syndrome iPSC-derived astrocytes. Similarly, mice in
      which mutant HRAS was expressed selectively in astrocytes exhibited experience
      independent increased accumulation of perineuronal net proteoglycans in cortex,
      as well as increased parvalbumin expression in interneurons, when compared to
      wild-type mice. Our data indicate that astrocytes expressing mutant HRAS
      dysregulate cortical maturation during development as shown by abnormal
      extracellular matrix remodeling and implicate excessive astrocyte-to-neuron
      signaling as a possible drug target for treating mental impairment and enhancing
      neuroplasticity. 

PMID- 25947162
TI  - Identification of a plant isoflavonoid that causes biliary atresia.
AB  - Biliary atresia (BA) is a rapidly progressive and destructive fibrotic disorder
      of unknown etiology affecting the extrahepatic biliary tree of neonates.
      Epidemiological studies suggest that an environmental factor, such as a virus or
      toxin, is the cause of the disease, although none have been definitively
      established. Several naturally occurring outbreaks of BA in Australian livestock
      have been associated with the ingestion of unusual plants by pregnant animals
      during drought conditions. We used a biliary secretion assay in zebrafish to
      isolate a previously undescribed isoflavonoid, biliatresone, from Dysphania
      species implicated in a recent BA outbreak. This compound caused selective
      destruction of the extrahepatic, but not intrahepatic, biliary system of larval
      zebrafish. A mutation that enhanced biliatresone toxicity mapped to a region of
      the zebrafish genome that has conserved synteny with an established human BA
      susceptibility locus. The toxin also caused loss of cilia in neonatal mouse
      extrahepatic cholangiocytes in culture and disrupted cell polarity and monolayer
      integrity in cholangiocyte spheroids. Together, these findings provide direct
      evidence that BA could be initiated by perinatal exposure to an environmental
      toxin. 

PMID- 25947164
TI  - Point-of-care quantification of blood-borne filarial parasites with a mobile
      phone microscope.
AB  - Parasitic helminths cause debilitating diseases that affect millions of people in
      primarily low-resource settings. Efforts to eliminate onchocerciasis and
      lymphatic filariasis in Central Africa through mass drug administration have been
      suspended because of ivermectin-associated serious adverse events, including
      death, in patients infected with the filarial parasite Loa loa. To safely
      administer ivermectin for onchocerciasis or lymphatic filariasis in regions co
      endemic with L. loa, a strategy termed "test and (not) treat" has been proposed
      whereby those with high levels of L. loa microfilariae (>30,000/ml) that put them
      at risk for life-threatening serious adverse events are identified and excluded
      from mass drug administration. To enable this, we developed a mobile phone-based
      video microscope that automatically quantifies L. loa microfilariae in whole
      blood loaded directly into a small glass capillary from a fingerprick without the
      need for conventional sample preparation or staining. This point-of-care device
      automatically captures and analyzes videos of microfilarial motion in whole blood
      using motorized sample scanning and onboard motion detection, minimizing input
      from health care workers and providing a quantification of microfilariae per
      milliliter of whole blood in under 2 min. To validate performance and usability
      of the mobile phone microscope, we tested 33 potentially Loa-infected patients in
      Cameroon and confirmed that automated counts correlated with manual thick smear
      counts (94% specificity; 100% sensitivity). Use of this technology to exclude
      patients from ivermectin-based treatment at the point of care in Loa-endemic
      regions would allow resumption/expansion of mass drug administration programs for
      onchocerciasis and lymphatic filariasis in Central Africa. 

PMID- 25947163
TI  - Collagen degradation and MMP9 activation by Enterococcus faecalis contribute to
      intestinal anastomotic leak.
AB  - Even under the most expert care, a properly constructed intestinal anastomosis
      can fail to heal, resulting in leakage of its contents, peritonitis, and sepsis.
      The cause of anastomotic leak remains unknown, and its incidence has not changed
      in decades. We demonstrate that the commensal bacterium Enterococcus faecalis
      contributes to the pathogenesis of anastomotic leak through its capacity to
      degrade collagen and to activate tissue matrix metalloproteinase 9 (MMP9) in host
      intestinal tissues. We demonstrate in rats that leaking anastomotic tissues were
      colonized by E. faecalis strains that showed an increased collagen-degrading
      activity and also an increased ability to activate host MMP9, both of which
      contributed to anastomotic leakage. We demonstrate that the E. faecalis genes
      gelE and sprE were required for E. faecalis-mediated MMP9 activation. Either
      elimination of E. faecalis strains through direct topical antibiotics applied to
      rat intestinal tissues or pharmacological suppression of intestinal MMP9
      activation prevented anastomotic leak in rats. In contrast, the standard
      recommended intravenous antibiotics used in patients undergoing colorectal
      surgery did not eliminate E. faecalis at anastomotic tissues nor did they prevent
      leak in our rat model. Finally, we show in humans undergoing colon surgery and
      treated with the standard recommended intravenous antibiotics that their
      anastomotic tissues still contained E. faecalis and other bacterial strains with
      collagen-degrading/MMP9-activating activity. We suggest that intestinal microbes
      with the capacity to produce collagenases and to activate host metalloproteinase
      MMP9 may break down collagen in the intestinal tissue contributing to anastomotic
      leak. 

PMID- 25947165
TI  - Prime-boost vaccination with chimpanzee adenovirus and modified vaccinia Ankara
      encoding TRAP provides partial protection against Plasmodium falciparum infection
      in Kenyan adults.
AB  - Protective immunity to the liver stage of the malaria parasite can be conferred
      by vaccine-induced T cells, but no subunit vaccination approach based on cellular
      immunity has shown efficacy in field studies. We randomly allocated 121 healthy
      adult male volunteers in Kilifi, Kenya, to vaccination with the recombinant viral
      vectors chimpanzee adenovirus 63 (ChAd63) and modified vaccinia Ankara (MVA),
      both encoding the malaria peptide sequence ME-TRAP (the multiple epitope string
      and thrombospondin-related adhesion protein), or to vaccination with rabies
      vaccine as a control. We gave antimalarials to clear parasitemia and conducted
      PCR (polymerase chain reaction) analysis on blood samples three times a week to
      identify infection with the malaria parasite Plasmodium falciparum. On Cox
      regression, vaccination reduced the risk of infection by 67% [95% confidence
      interval (CI), 33 to 83%; P = 0.002] during 8 weeks of monitoring. T cell
      responses to TRAP peptides 21 to 30 were significantly associated with protection
      (hazard ratio, 0.24; 95% CI, 0.08 to 0.75; P = 0.016). 

PMID- 25947166
TI  - Identification of new Saccharomyces cerevisiae variants of the MET2 and SKP2
      genes controlling the sulfur assimilation pathway and the production of
      undesirable sulfur compounds during alcoholic fermentation.
AB  - BACKGROUND: Wine yeasts can produce undesirable sulfur compounds during alcoholic
      fermentation, such as SO2 and H2S, in variable amounts depending mostly on the
      yeast strain but also on the conditions. However, although sulfur metabolism has
      been widely studied, some of the genetic determinants of differences in sulfite
      and/or sulfide production between wine yeast strains remain to be identified. In
      this study, we used an integrated approach to decipher the genetic determinants
      of variation in the production of undesirable sulfur compounds. RESULTS: We
      examined the kinetics of SO2 production by two parental strains, one high and one
      low sulfite producer. These strains displayed similar production profiles but
      only the high-sulfite producer strain continued to produce SO2 in the stationary
      phase. Transcriptomic analysis revealed that the low-sulfite producer strain
      overexpressed genes of the sulfur assimilation pathway, which is the mark of a
      lower flux through the pathway consistent with a lower intracellular
      concentration in cysteine. A QTL mapping strategy then enabled us to identify
      MET2 and SKP2 as the genes responsible for these phenotypic differences between
      strains and we identified new variants of these genes in the low-sulfite producer
      strain. MET2 influences the availability of a metabolic intermediate, O
      acetylhomoserine, whereas SKP2 affects the activity of a key enzyme of the sulfur
      assimilation branch of the pathway, the APS kinase, encoded by MET14.
      Furthermore, these genes also affected the production of propanol and
      acetaldehyde. These pleiotropic effects are probably linked to the influence of
      these genes on interconnected pathways and to the chemical reactivity of sulfite
      with other metabolites. CONCLUSIONS: This study provides new insight into the
      regulation of sulfur metabolism in wine yeasts and identifies variants of MET2
      and SKP2 genes, that control the activity of both branches of the sulfur amino
      acid synthesis pathway and modulate sulfite/sulfide production and other related
      phenotypes. These results provide novel targets for the improvement of wine yeast
      strains.

PMID- 25947167
TI  - Electroacupuncture analgesia is associated with increased serum brain-derived
      neurotrophic factor in chronic tension-type headache: a randomized, sham
      controlled, crossover trial.
AB  - BACKGROUND: Chronic tension-type headache (CTTH) is characterized by almost daily
      headaches and central sensitization, for which electroacupuncture (EA) might be
      effective. The central nervous system (CNS) plasticity can be tracked in serum
      using the brain-derived neurotrophic factor (BDNF), a neuroplasticity mediator.
      Thus, we tested the hypothesis that EA analgesia in CTTH is related to
      neuroplasticity indexed by serum BDNF. METHODS: We enrolled females aged 18-60
      years with CTTH in a randomized, blinded, placebo-controlled crossover trial,
      comparing ten EA sessions applied for 30 minutes (2-10 Hz, intensity by
      tolerance) in cervical areas twice per week vs. a sham intervention. Treatment
      periods were separated by two washout weeks. Pain on the 10-cm visual analog
      scale (VAS) and serum BDNF were assessed as primary outcomes. RESULTS: Thirty
      four subjects underwent randomization, and twenty-nine completed the protocol. EA
      was superior to sham to alleviate pain (VAS scores 2.38 +/- 1.77 and 3.02 +/-
      2.49, respectively, P = 0.005). The VAS scores differed according to the
      intervention sequence, demonstrating a carryover effect (P < 0.05). Using
      multiple regression, serum BDNF was adjusted for the Hamilton depression rating
      scale (HDRS) and the VAS scores (r-squared = 0.07, standard beta coefficients = 
      0.2 and -0.14, respectively, P < 0.001). At the end of the first intervention
      period, the adjusted BDNF was higher in the EA phase (29.31 +/- 3.24, 27.53 +/-
      2.94 ng/mL, Cohen's d = 0.55). CONCLUSION: EA analgesia is related to
      neuroplasticity indexed by the adjusted BDNF. EA modulation of pain and BDNF
      occurs according to the CNS situation at the moment of its administration, as it
      was related to depression and the timing of its administration.

PMID- 25947169
TI  - In vivo Ca2+ buffering capacity and microvascular oxygen pressures following
      muscle contractions in diabetic rat skeletal muscles: fiber-type specific
      effects.
AB  - In Type 1 diabetes, skeletal muscle resting intracellular Ca(2+) concentration
      ([Ca(2+)]i) homeostasis is impaired following muscle contractions. It is unclear
      to what degree this behavior is contingent upon fiber type and muscle oxygenation
      conditions. We tested the hypotheses that: 1) the rise in resting [Ca(2+)]i
      evident in diabetic rat slow-twitch (type I) muscle would be exacerbated in fast
      twitch (type II) muscle following contraction; and 2) these elevated [Ca(2+)]i
      levels would relate to derangement of microvascular partial pressure of oxygen
      (PmvO2 ) rather than sarcoplasmic reticulum dysfunction per se. Adult male Wistar
      rats were divided randomly into diabetic (DIA: streptozotocin ip) and healthy
      (CONT) groups. Four weeks later extensor digitorum longus (EDL, predominately
      type II fibers) and soleus (SOL, predominately type I fibers) muscle contractions
      were elicited by continuous electrical stimulation (120 s, 100 Hz). Ca(2+)
      imaging was achieved using fura 2-AM in vivo (i.e., circulation intact). DIA
      increased fatigability in EDL (P < 0.05) but not SOL. In recovery, SOL [Ca(2+)]i
      either returned to its resting baseline within 150 s (CONT 1.00 +/- 0.02 at 600
      s) or was not elevated in recovery at all (DIA 1.03 +/- 0.02 at 600 s, P > 0.05).
      In recovery, EDL CONT [Ca(2+)]i also decreased to values not different from
      baseline (1.06 +/- 0.01, P > 0.05) at 600 s. In marked contrast, EDL DIA
      [Ca(2+)]i remained elevated for the entire recovery period (i.e., 1.23 +/- 0.03
      at 600 s, P < 0.05). The inability of [Ca(2+)]i to return to baseline in EDL DIA
      was not associated with any reduction of SR Ca(2+)-ATPase (SERCA) 1 or SERCA2
      protein levels (both increased 30-40%, P < 0.05). However, Pmv(O2) recovery
      kinetics were markedly slowed in EDL such that mean Pmv(O2) was substantially
      depressed (CONT 27.9 +/- 2.0 vs. DIA 18.4 +/- 2.0 Torr, P < 0.05), and this
      behavior was associated with the elevated [Ca(2+)]i. In contrast, this was not
      the case for SOL (P > 0.05) in that neither [Ca(2+)]i nor Pmv(O2) were deranged
      in recovery with DIA. In conclusion, recovery of [Ca(2+)]i homeostasis is
      impaired in diabetic rat fast-twitch but not slow-twitch muscle in concert with
      reduced Pmv(O2) pressures.

PMID- 25947168
TI  - Angiotensin receptors alter myocardial infarction-induced remodeling of the
      guinea pig cardiac plexus.
AB  - Neurohumoral remodeling is fundamental to the evolution of heart disease. This
      study examined the effects of chronic treatment with an ACE inhibitor (captopril,
      3 mg.kg(-1).day(-1)), AT1 receptor antagonist (losartan, 3 mg.kg(-1).day(-1)), or
      AT2 receptor agonist (CGP42112A, 0.14 mg.kg(-1).day(-1)) on remodeling of the
      guinea pig intrinsic cardiac plexus following chronic myocardial infarction (MI).
      MI was surgically induced and animals recovered for 6 or 7 wk, with or without
      drug treatment. Intracellular voltage recordings from whole mounts of the cardiac
      plexus were used to monitor changes in neuronal responses to norepinephrine (NE),
      muscarinic agonists (bethanechol), or ANG II. MI produced an increase in neuronal
      excitability with NE and a loss of sensitivity to ANG II. MI animals treated with
      captopril exhibited increased neuronal excitability with NE application, while MI
      animals treated with CGP42112A did not. Losartan treatment of MI animals did not
      alter excitability with NE compared with untreated MIs, but these animals did
      show an enhanced synaptic efficacy. This effect on synaptic function was likely
      due to presynaptic AT1 receptors, since ANG II was able to reduce output to nerve
      fiber stimulation in control animals, and this effect was prevented by inclusion
      of losartan in the bath solution. Analysis of AT receptor expression by Western
      blot showed a decrease in both AT1 and AT2 receptors with MI that was reversed by
      all three drug treatments. These data indicate that neuronal remodeling of the
      guinea pig cardiac plexus following MI is mediated, in part, by activation of
      both AT1 and AT2 receptors. 

PMID- 25947170
TI  - Sex differences in proximal and distal nephron function contribute to the
      mechanism of idiopathic hypercalcuria in calcium stone formers.
AB  - Idiopathic hypercalciuria (IH) is a common familial trait among patients with
      calcium nephrolithiasis. Previously, we have demonstrated that hypercalciuria is
      primarily due to reduced renal proximal and distal tubule calcium reabsorption.
      Here, using measurements of the clearances of sodium, calcium, and endogenous
      lithium taken from the General Clinical Research Center, we test the hypothesis
      that patterns of segmental nephron tubule calcium reabsorption differ between the
      sexes in IH and normal subjects. When the sexes are compared, we reconfirm the
      reduced proximal and distal calcium reabsorption. In IH women, distal nephron
      calcium reabsorption is decreased compared to normal women. In IH men, proximal
      tubule calcium reabsorption falls significantly, with a more modest reduction in
      distal calcium reabsorption compared to normal men. Additionally, we demonstrate
      that male IH patients have lower systolic blood pressures than normal males. We
      conclude that women and men differ in the way they produce the hypercalciuria of
      IH, with females reducing distal reabsorption and males primarily reducing
      proximal tubule function. 

PMID- 25947171
TI  - Sympathetic neural recruitment strategies: responses to severe chemoreflex and
      baroreflex stress.
AB  - This study tested the hypothesis that neural coding patterns exist within the
      autonomic nervous system. We investigated sympathetic axonal recruitment
      strategies in humans during chemoreflex- and baroreflex-mediated
      sympathoexcitation using a novel action potential (AP) analysis technique. Muscle
      sympathetic nerve activity (microneurography) was collected in 11 young
      individuals (6 females) during baseline and two subsequent protocols: 1) severe
      chemoreflex stimulation (maximal end-inspiratory apnea following rebreathe), and
      2) severe baroreceptor unloading (-80 mmHg lower body negative pressure; LBNP).
      When compared with each respective baseline, apnea and LBNP increased AP
      frequency and mean AP content per sympathetic burst (all P < 0.01). When APs were
      binned according to peak-to-peak amplitude (i.e., into "clusters"), total
      clusters detected increased during both apnea (Delta7 +/- 5; P = 0.0009) and LBNP
      (Delta11 +/- 8; P = 0.0012) compared with baseline. This was concomitant to an
      increased number of active clusters per burst during apnea (Delta3 +/- 1; P <
      0.0001) and LBNP (Delta3 +/- 3; P = 0.0076). At baseline and during apnea (R(2) =
      0.98; P < 0.0001) and LBNP (R(2) = 0.95; P < 0.0001), a pattern emerged whereby
      AP cluster latency decreased as cluster size increased. Furthermore, the AP
      cluster latency profile was shifted downward during apnea (~53 ms) and upward
      during LBNP (~31 ms). The data indicate that variations in synaptic delays and
      latent subpopulations of larger axons exist as recruitment strategies for
      sympathetic outflow. The synaptic delay component appears to express reflex
      specificity, whereas latent subpopulation recruitment demonstrates sensitivity to
      stress severity.

PMID- 25947173
TI  - Trends In Health Insurance Enrollment, 2013-15.

PMID- 25947174
TI  - Never say never about our child.

PMID- 25947172
TI  - Systemic hypotensive effects of testosterone are androgen structure-specific and
      neuronal nitric oxide synthase-dependent.
AB  - Testosterone (TES) and other androgens exert a direct vasorelaxing action on the
      vasculature in vitro that is structurally specific and independent of cytosolic
      androgen receptor (AR). The effects of intravenous androgen infusions on mean
      arterial blood pressure (BP) and heart rate (HR) were determined in conscious,
      unrestrained, chronically catheterized, ganglionically blocked (hexamethonium,
      HEX; 30 mg/kg ip) male Sprague-Dawley (SD) and testicular-feminized male (Tfm; AR
      deficient) rats, 16-20 wk of age. BP and HR were recorded at baseline and with
      increasing doses of androgens (0.375-6.00 MUmol.kg(-1).min(-1) iv; 10 min/dose).
      Data are expressed as means +/- SE (n = 5-8 rats/group). In SD rats, baseline BP
      and HR averaged 103 +/- 4 mmHg and 353 +/- 12 beats/min (bpm). TES produced a
      dose-dependent reduction in BP to a low of 87 +/- 4 mmHg (Delta16%), while HR was
      unchanged (354 +/- 14 bpm). Neither BP (109 +/- 3 mmHg) nor HR (395 +/- 13 bpm)
      were altered by vehicle (10% EtOH in 0.9% saline; 0.15 ml.kg(-1).min(-1), iv). In
      Tfm, TES produced a similar reduction in BP (99 +/- 3 to 86 +/- 3 mmHg,
      Delta13%); HR was unchanged (369 +/- 18 bpm). In SD, 5beta-dihydrotestosterone
      (genomically inactive metabolite) produced a greater reduction in BP than TES
      (102 +/- 2 to 79 +/- 2 mmHg, Delta23%); HR was unchanged (361 +/- 9). A 20-MUg iv
      bolus of sodium nitroprusside in both SD and Tfm rats reduced BP 30-40 mmHg,
      while HR was unchanged, confirming blockade by HEX. Pretreatment of SD rats with
      neuronal nitric oxide synthase (nNOS) inhibitor (S-methyl-thiocitrulline, SMTC;
      20 MUg.kg(-1).min(-1) * 30 min) abolished the hypotensive effects of TES infusion
      on BP (104 +/- 2 vs. 101 +/- 2 mmHg) and HR (326 +/- 11 vs. 324 +/- 8 bpm). These
      data suggest the systemic hypotensive effect of TES and other androgens involves
      a direct vasodilatory action on the peripheral vasculature which, like the effect
      observed in isolated arteries, is structurally specific and AR-independent, and
      involves activation of nNOS. 

PMID- 25947175
TI  - Autism Developmental Profiles and Cooperation with Oral Health Screening.
AB  - To determine the associations between autism developmental profiles and
      cooperation with an oral health screening among preschool children with autism
      spectrum disorders (ASDs). A random sample of Special Child Care Centres
      registered with the Government Social Welfare Department in Hong Kong was
      selected (19 out of 37 Centres). All preschool children with ASDs were invited to
      participate in the oral health survey and 347 children agreed to participate
      (among 515 invited). A checklist of autism developmental profiles: (1) level of
      cognitive functioning, (2) social skills development, (3) communication skills
      development, (4) reading skills and (5) challenging behaviours was ascertained.
      Feasibility of conducting oral health screening in preschool children with ASDs
      was associated with their cognitive functioning (p = 0.001), social skills
      development (p = 0.002), communication skills development (p < 0.001), reading
      skills (p < 0.001) and challenging behaviours (p = 0.06). In regression analyses
      accounting for age (in months) and gender, inability to cooperate with an oral
      health screening was associated with high level of challenging behaviours (OR
      10.50, 95 % CI 2.89-38.08, p < 0.001) and reduced cognitive functioning (OR 5.29,
      95 % CI 1.14-24.61, p = 0.034). Age (in months) was positively associated with
      likelihood of cooperative behaviour with an oral health screening (OR 1.06, 95 %
      CI 1.03, 1.08, p < 0.001). Feasibility of conducting population-wide oral health
      screening among preschool children with ASDs is associated with their
      developmental profiles; and in particular levels of cognitive functioning, and
      challenging behaviours.

PMID- 25947177
TI  - An integrin-targeted photoactivatable Pt(IV) complex as a selective anticancer
      pro-drug: synthesis and photoactivation studies.
AB  - A new anticancer agent based on the conjugation of a photoactivatable Pt(IV) pro
      drug to a cyclic RGD-containing peptide is described. Upon visible light
      irradiation, phototoxicity was induced preferentially in SK-MEL-28 melanoma
      cancer cells overexpressing alphaVbeta3 integrin compared to control DU-145 human
      prostate carcinoma cells.

PMID- 25947176
TI  - Development of a comparative genomic fingerprinting assay for rapid and high
      resolution genotyping of Arcobacter butzleri.
AB  - BACKGROUND: Molecular typing methods are critical for epidemiological
      investigations, facilitating disease outbreak detection and source
      identification. Study of the epidemiology of the emerging human pathogen
      Arcobacter butzleri is currently hampered by the lack of a subtyping method that
      is easily deployable in the context of routine epidemiological surveillance. In
      this study we describe a comparative genomic fingerprinting (CGF) method for high
      resolution and high-throughput subtyping of A. butzleri. Comparative analysis of
      the genome sequences of eleven A. butzleri strains, including eight strains newly
      sequenced as part of this project, was employed to identify accessory genes
      suitable for generating unique genetic fingerprints for high-resolution subtyping
      based on gene presence or absence within a strain. RESULTS: A set of eighty-three
      accessory genes was used to examine the population structure of a dataset
      comprised of isolates from various sources, including human and non-human
      animals, sewage, and river water (n=156). A streamlined assay (CGF40) based on a
      subset of 40 genes was subsequently developed through marker optimization. High
      levels of profile diversity (121 distinct profiles) were observed among the 156
      isolates in the dataset, and a high Simpson's Index of Diversity (ID) observed
      (ID > 0.969) indicate that the CGF40 assay possesses high discriminatory power.
      At the same time, our observation that 115 isolates in this dataset could be
      assigned to 29 clades with a profile similarity of 90% or greater indicates that
      the method can be used to identify clades comprised of genetically similar
      isolates. CONCLUSIONS: The CGF40 assay described herein combines high resolution
      and repeatability with high throughput for the rapid characterization of A.
      butzleri strains. This assay will facilitate the study of the population
      structure and epidemiology of A. butzleri.

PMID- 25947178
TI  - [A Methodological Quality Assessment of South Korean Nursing Research using
      Structural Equation Modeling in South Korea].
AB  - PURPOSE: The purpose of this study was to evaluate the methodological quality of
      nursing studies using structural equation modeling in Korea. METHODS: Databases
      of KISS, DBPIA, and National Assembly Library up to March 2014 were searched
      using the MeSH terms 'nursing', 'structure', 'model'. A total of 152 studies were
      screened. After removal of duplicates and non-relevant titles, 61 papers were
      read in full. RESULTS: Of the sixty-one articles retrieved, 14 studies were
      published between 1992 and 2000, 27, between 2001 and 2010, and 20, between 2011
      and March 2014. The methodological quality of the review examined varied
      considerably. CONCLUSION: The findings of this study suggest that more rigorous
      research is necessary to address theoretical identification, two indicator rule,
      distribution of sample, treatment of missing values, mediator effect,
      discriminant validity, convergent validity, post hoc model modification,
      equivalent models issues, and alternative models issues should be undergone.
      Further research with robust consistent methodological study designs from model
      identification to model respecification is needed to improve the validity of the
      research.

PMID- 25947179
TI  - [Effects of Cognitive Behavioral Therapy on Attention Deficit Hyperactivity
      Disorder among School-aged Children in Korea: A Meta-Analysis].
AB  - PURPOSE: This study was a meta-analysis designed to identify effects of Cognitive
      Behavioral Therapy (CBT) interventions in alleviating main symptoms of Attention
      Deficit Hyperactivity Disorder (ADHD) among school-aged children in Korea.
      METHODS: Examination of several databases including Research Information Sharing
      Service, Korean Studies Information Service System, Data Base Periodical
      Information Academic and hand-searched article references, resulted in
      identification of 1,298 studies done between 2000 and 2013 of which 21 met the
      inclusion criteria. Comprehensive Meta-Analysis version 2.0 was used to analyze
      effect sizes, explore possible causes of heterogeneity, and check publication
      bias with a funnel plot and its trim-and-fill analysis. RESULTS: Overall effect
      size of CBT intervention was large (g=1.08) along with each outcome of self
      control (g=1.26), lack of attention (g=1.02), social skills (g=0.92), and
      hyperactivity (g=0.92). For heterogeneity, moderator analysis was performed, but
      no significant differences were found between the RCT (Randomized Controlled
      Trials) group and the NRCT (Non RCT) group. Also, meta-regression was performed
      using sample size, number of sessions, and length of session as predictors, but
      no statistically significant moderators were found. Finally, a funnel plot along
      with trim-and-fill analysis was produced to check for publication bias, but no
      significant bias was detected. CONCLUSION: Based on these findings, there is
      clear evidence that CBT intervention has significant positive effects on the main
      symptoms of school-aged children suffering ADHD. Further research is needed to
      target diverse age groups with ADHD along with more RCT studies to improve the
      effectiveness of the CBT intervention.

PMID- 25947180
TI  - [Effects of Sexual Intercourse on Suicidal Behaviors among Adolescents in South
      Korea].
AB  - PURPOSE: For the current article an examination was done as to whether engaging
      in sexual intercourse before or during adolescence has a negative impact on the
      suicidal behaviors of suicide ideation, suicide attempt, and suicide lethality
      and whether the impact varies according to the context of sexual intercourse
      and/or gender. METHODS: Adolescents who experienced casual sex and romantic sex
      were compared to adolescents who retained their virginity. Data was from samples
      drawn from the three waves (2010~2012) of the Korea Youth Risk Behavior Web-Based
      Survey. Logistic models were used to adjust for a wide array of confounding
      variables. RESULTS: Any type of sexual intercourse increases risk of all suicidal
      behaviors. Sexual intercourse in a romantic relationship exhibits enhanced risk
      of suicidal behaviors compared to casual sex. Adjusting for experience of sexual
      violence, however, decreases risk of romantic sex substantially, turning some
      estimates statistically insignificant. In addition, risks for suicide lethality
      are greater for girls than boys. CONCLUSION: Romantic sex put adolescents at
      higher risk for suicidal behaviors than casual sex owing to prevalent sexual
      violence in the relationships. Girls suffer more substantively adverse outcomes
      than boys. These results suggest that adolescents will benefit from comprehensive
      education on sexuality and sexual behaviors regarding how to form and maintain a
      romantic relationship that is characterized by personal integrity and mutual
      respect. It is also important to help victims of sexual violence recover from
      traumatic events by providing emotional support and effective counseling.

PMID- 25947181
TI  - [Effects of a Multi-disciplinary Approached, Empowerment Theory Based Self
      management Intervention in Older Adults with Chronic Illness].
AB  - PURPOSE: The purpose of this study was to develop a multi-disciplinary self
      management intervention based on empowerment theory and to evaluate the
      effectiveness of the intervention for older adults with chronic illness. METHODS:
      A randomized controlled trial design was used with 43 Korean older adults with
      chronic illness (Experimental group=22, Control group=21). The intervention
      consisted of two phases: (1) 8-week multi-disciplinary, team guided, group-based
      health education, exercise session, and individual empowerment counseling, (2) 16
      week self-help group activities including weekly exercise and group discussion to
      maintain acquired self-management skills and problem-solving skills. Baseline, 8
      week, and 24-week assessments measured health empowerment, exercise self
      efficacy, physical activity, and physical function. RESULTS: Health empowerment,
      physical activity, and physical function in the experimental group increased
      significantly compared to the control group over time. Exercise self-efficacy
      significantly increased in experimental group over time but there was no
      significant difference between the two groups. CONCLUSION: The self-management
      program based on empowerment theory improved health empowerment, physical
      activity, and physical function in older adults. The study finding suggests that
      a health empowerment strategy may be an effective approach for older adults with
      multiple chronic illnesses in terms of achieving a sense of control over their
      chronic illness and actively engaging self-management.

PMID- 25947182
TI  - [Depression and caregiving burden in families of patients with amyotrophic
      lateral sclerosis].
AB  - PURPOSE: The purpose of this study was to describe depression, caregiving burden
      and the correlation of the two variables in the families of patients with
      amyotrophic lateral sclerosis (ALS) and to clarify factors predicting caregiving
      burden. METHODS: A descriptive and cross-sectional study was conducted with 139
      family members who provided care to patients with ALS. The characteristics of
      patients and families, Korean-Beck Depression Inventory (K-BDI), Korean version
      of Zarit Burden Interview (K-ZBI) and Korean-Amyotrophic Lateral Sclerosis
      Functional Rating Scale - Revised (K-ALSFRS-R) were used as study measures.
      RESULTS: The mean score for K-BDI was 19.39 out of 63 suggesting sub-clinical
      depression and 38.2% of the family members exhibited depression. The mean score
      for K-ZBI was 66.03 out of 88. The predictors for K-ZBI were K-BDI, age of family
      member, length of time spent per day in caring, relationship to patient and K
      ALSFRS-R. CONCLUSION: The results of this study suggest that levels of depression
      and caregiving burden are high among family members caring for patients with ALS.
      As depression is associated with caregiving burden, screening and emotional
      supports should be provided to reduce the burden of care for these family.
      Support programs to alleviate the care burden are also needed, considering family
      demographics, time per day in caring giving and K-ALSFRS-R.

PMID- 25947183
TI  - [Development of a prediction model for postpartum depression: based on the
      mediation effect of antepartum depression].
AB  - PURPOSE: This study was done to develop a prediction model for postpartum
      depression by verifying the mediation effect of antepartum depression. A
      hypothesized model was developed based on literature reviews and predictors of
      postpartum depression by Beck. METHODS: Data were collected from 186 pregnant
      women who had a gestation period of more than 32 weeks and were patients at a
      maternity hospital, two obstetrics and gynecology specialized hospitals, or the
      outpatient clinic of K medical center. Data were analysed with descriptive
      statistics, correlation and exploratory factor analysis using the SPSS/WIN 18.0
      and AMOS 18.0 programs. RESULTS: The final modified model had good fit indices.
      Parenting stress, antepartum depression and postpartum family support had
      statistically significant effects on postpartum depression, and defined 74.7% of
      total explained variance of postpartum depression. Antepartum depression had
      significant mediation effects on postpartum depression from stress in pregnancy
      and self-esteem. CONCLUSION: The results of this study suggest that it is
      important to develop nursing interventions including strategies to reduce
      parenting stress and improve postpartum family support in order to prevent
      postpartum depression. Especially, it is necessary to detect and treat antepartum
      depression early to prevent postpartum depression as antepartum depression can
      affect postpartum depression by mediating antepartum factors.

PMID- 25947184
TI  - [Effect and Path Analysis of Laughter Therapy on Serotonin, Depression and
      Quality of Life in Middle-aged Women].
AB  - PURPOSE: This study was done to examine how laughter therapy impacts serotonin
      levels, QOL and depression in middle-aged women and to perform a path analysis
      for verification of the effects. METHODS: A quasi-experimental study employing a
      nonequivalent control group and pre-post design was conducted. Participants were
      64 middle-aged women (control=14 and experimental=50 in 3 groups according to
      level of depression). The intervention was conducted five times a week for a
      period of 2 weeks and the data analysis was conducted using repeated measures
      ANOVA, ANCOVA and LISREL. RESULTS: Results showed that pre serotonin and QOL in
      women with severe depression were the lowest. Serotonin in the experimental
      groups increased after the 10th intervention (p=.006) and the rise was the
      highest in the group with severe depression (p=.001). Depression in all groups
      decreased after the 5th intervention (p=.022) and the biggest decline was
      observed in group with severe depression (p=.007). QOL of the moderate and severe
      groups increased after the 10th intervention (p=.049), and the increase rate was
      highest in group with severe depression (p<.006). Path analysis revealed that
      laughter therapy did not directly affect depression, but its effect was
      indirectly meditated through serotonin variation (p<.001). CONCLUSION: Results
      indicate that serotonin activation through laughter therapy can help middle-aged
      women by lessening depression and providing important grounds for depression
      control.

PMID- 25947185
TI  - [Successful Aging of Korean Older Adults based on Rowe and Kahn's Model: A
      Comparative Study According to the Use of Community Senior Facilities].
AB  - PURPOSE: This study was conducted to examine the prevalence of successful aging
      and factors influencing successful aging. METHODS: This was a secondary analysis
      study. Data were analyzed from 10,462 elderly people who participated in the 2011
      National Elderly Survey. According to the use of community senior facilities,
      participants were divided into 4 groups: those who used senior centers (group A,
      n=580), village senior clubs (group B, n=3,240), both of the 2 facilities (group
      C, n=339), and neither of the 2 facilities (group D, n=6,303). Cross-tabulation
      and logistic regression were performed. RESULTS: The prevalence of successful
      aging was highest in group C (20.94%) and lowest in group D (10.41%). The
      physical & mental function and active engagement domains were highest in group C,
      while they were lowest in group D. The disease & risk factors domain were highest
      in group A, while lowest in group B. An educational level of middleschool or
      higher and income level in the third or higher quintile were significant factors
      for predicting successful aging in all groups. CONCLUSION: These results provide
      a basis for designing prevention and management programs as interventions to
      increase the prevalence of successful aging in Korean older adults.

PMID- 25947186
TI  - [A Validation Study of the Modified Korean Version of Ethical Leadership at Work
      Questionnaire (K-ELW)].
AB  - PURPOSE: The purpose of this study was to validate the Korean version of the
      Ethical Leadership at Work questionnaire (K-ELW) that measures RNs' perceived
      ethical leadership of their nurse managers. METHODS: The strong validation
      process suggested by Benson (1998), including translation and cultural adaptation
      stage, structural stage, and external stage, was used. Participants were 241 RNs
      who reported their perceived ethical leadership using both the pre-version of K
      ELW and a previously known Ethical Leadership Scale, and interactional justice of
      their managers, as well as their own demographics, organizational commitment and
      organizational citizenship behavior. Data analyses included descriptive
      statistics, Pearson correlation coefficients, reliability coefficients,
      exploratory factor analysis, and confirmatory factor analysis. SPSS 19.0 and Amos
      18.0 versions were used. RESULTS: A modified K-ELW was developed from construct
      validity evidence and included 31 items in 7 domains: People orientation, task
      responsibility fairness, relationship fairness, power sharing, concern for
      sustainability, ethical guidance, and integrity. Convergent validity,
      discriminant validity, and concurrent validity were supported according to the
      correlation coefficients of the 7 domains with other measures. CONCLUSION: The
      results of this study provide preliminary evidence that the modified K-ELW can be
      adopted in Korean nursing organizations, and reliable and valid ethical
      leadership scores can be expected.

PMID- 25947187
TI  - [Effects of an Integrated Internet Addiction Prevention Program on Elementary
      Students' Self-regulation and Internet Addiction].
AB  - PURPOSE: The purpose of this study was to develop an integrated internet
      addiction prevention program and test its effects on the self-regulation and
      internet addiction of elementary students who are at risk for internet addiction.
      METHODS: A quasi-experimental study with a nonequivalent control group pretest
      posttest design was used. Participants were assigned to the experimental group
      (n=28) or control group (n=28). Contents of the program developed in this study
      included provision of information about internet addiction, interventions for
      empowerment and methods of behavioral modification. A pre-test and two post-tests
      were done to identify the effects of the program and their continuity. Effects
      were testified using Repeated measures ANOVA, simple effect analysis, and Time
      Contrast. RESULTS: The self-regulation of the experimental group after the
      program was significantly higher than the control group. The score for internet
      addiction self-diagnosis and the internet use time in the experimental group were
      significantly lower than the control group. CONCLUSION: The effects of the
      integrated internet addiction prevention program for preventing internet
      addiction in elementary students at risk for internet addiction were validated.

PMID- 25947188
TI  - [Effects of death anxiety and meaning of life on somatization of grandparent
      raising grandchildren].
AB  - PURPOSE: This study was conducted in order to examine the effects of death
      anxiety and meaning of life on somatization of grandparents raising
      grandchildren. METHODS: A convenience sample of 92 elderly grandparents raising
      grandchildren was recruited. The study instrument for death anxiety was the 5
      point 15 items scale designed by Templer and translated by Ko, Choi, & Lee and
      for meaning of life, the 7-point 10-items scale by Steger, Frazier, Oishi & Kaler
      and translated by Won, Kim & Kwon. For somatization, the 5-point 12 items scale
      designed by Derogatis and translated by Kim, Kim & Won was used. Collected data
      were analyzed with descriptive statistics, independent t-test, one-way ANOVA,
      Pearson Correlation and regression using the SPSS 21.0 program. RESULTS: Average
      scores were 3.55 for death anxiety, 3.43 for meaning of life, and 2.74 for
      somatization. Death anxiety had the highest positive correlation with
      somatization. Meaning of life was negatively correlated with death anxiety and
      somatization. Death anxiety and health status were shown to influence
      somatization but meaning of life was not shown to influence somatization.
      CONCLUSION: The research results indicate that death anxiety and health status
      influence somatization in grandparents raising grandchildren. These results also
      provide basic information on the importance of nursing interventions in which the
      variables influencing somatization in grandparents raising grandchildren are
      considered.

PMID- 25947189
TI  - [Influence of Uncertainty and Uncertainty Appraisal on Self-management in
      Hemodialysis Patients].
AB  - PURPOSE: This study was done to examine the relation of uncertainty, uncertainty
      appraisal, and self-management in patients undergoing hemodialysis, and to
      identify factors influencing self-management. METHODS: A convenience sample of 92
      patients receiving hemodialysis was selected. Data were collected using a
      structured questionnaire and medical records. The collected data were analyzed
      using descriptive statistics, t-test, ANOVA, Pearson correlations and multiple
      regression analysis with the SPSS/WIN 20.0 program. RESULTS: The participants
      showed a moderate level of uncertainty with the highest score being for ambiguity
      among the four uncertainty subdomains. Scores for uncertainty danger or
      opportunity appraisals were under the mid points. The participants were found to
      perform a high level of self-management such as diet control, management of
      arteriovenous fistula, exercise, medication, physical management, measurements of
      body weight and blood pressure, and social activity. The self-management of
      participants undergoing hemodialysis showed a significant relationship with
      uncertainty and uncertainty appraisal. The significant factors influencing self
      management were uncertainty, uncertainty opportunity appraisal, hemodialysis
      duration, and having a spouse. These variables explained 32.8% of the variance in
      self-management. CONCLUSION: The results suggest that intervention programs to
      reduce the level of uncertainty and to increase the level of uncertainty
      opportunity appraisal among patients would improve the self-management of
      hemodialysis patients.

PMID- 25947190
TI  - [Model for unplanned self extubation of ICU patients using system dynamics
      approach].
AB  - PURPOSE: In this study a system dynamics methodology was used to identify
      correlation and nonlinear feedback structure among factors affecting unplanned
      extubation (UE) of ICU patients and to construct and verify a simulation model.
      METHODS: Factors affecting UE were identified through a theoretical background
      established by reviewing literature and preceding studies and referencing various
      statistical data. Related variables were decided through verification of content
      validity by an expert group. A causal loop diagram (CLD) was made based on the
      variables. Stock & Flow modeling using Vensim PLE Plus Version 6.0 b was
      performed to establish a model for UE. RESULTS: Based on the literature review
      and expert verification, 18 variables associated with UE were identified and CLD
      was prepared. From the prepared CLD, a model was developed by converting to the
      Stock & Flow Diagram. Results of the simulation showed that patient stress,
      patient in an agitated state, restraint application, patient movability, and
      individual intensive nursing were variables giving the greatest effect to UE
      probability. To verify agreement of the UE model with real situations, simulation
      with 5 cases was performed. Equation check and sensitivity analysis on TIME STEP
      were executed to validate model integrity. CONCLUSION: Results show that
      identification of a proper model enables prediction of UE probability. This
      prediction allows for adjustment of related factors, and provides basic data do
      develop nursing interventions to decrease UE.

PMID- 25947191
TI  - [Gender difference in osteoporosis prevalence, awareness and treatment: based on
      the Korea national health and nutrition examination survey 2008~2011].
AB  - PURPOSE: The aim of the study was to assess and identify gender differences in
      factors associated with prevalence, awareness, and treatment of osteoporosis.
      METHODS: Data for 3,071 men and 3,635 women (age >= 50) from the Korea National
      Health and Nutrition Examination Survey 2008~2011 were included. Osteoporosis was
      defined by World Health Organization T-score criteria. Impact factors and odds
      ratios were analysed by gender using multivariate logistic regression. RESULTS:
      Osteoporosis prevalence rates were 7.0% in men and 40.1% in women. Osteopenia
      rates were 45.5% and 46.0% respectively. Among respondents with osteoporosis,
      7.6% men and 37.8% women were aware of their diagnosis. Also 5.7% men with
      osteoporosis and 22.8% women were treated. Higher prevalence was found among
      respondents who were older, at lower socioeconomic levels, with lower body mass
      index and shorter height in both genders, and among women with fracture history,
      and non-hormonal replacement therapy. Awareness and treatment rates for the risk
      groups were similar compared to the low risk controls for both genders. Fracture
      history increased awareness and treatment rates independently for both genders.
      Women with perceived poor health status and health screening had increased
      awareness and treatment rates, but not men. CONCLUSION: Results indicate that
      postmenopausal women have a higher prevalence of osteoporosis than men and
      awareness and treatment rates were higher than for men. Despite gender difference
      in prevalence, osteoporosis was underdiagnosed and undertreated for both genders.
      Specialized public education and routine health screenings according to gender
      could be effective strategies to increase osteoporosis awareness and treatment.

PMID- 25947192
TI  - Breastfeeding Initiation and Continuation by Employment Status among Korean
      Women.
AB  - PURPOSE: The objective of this study was to examine the factors associated with
      initiation and continuation of breastfeeding among Korean women in relation to
      their employment status. METHODS: Data were collected using a web-based self
      administered questionnaire from 1,031 Korean mothers living in Seoul with babies
      younger than 24 months. Demographic characteristics, education on breastfeeding,
      rooming in, breastfeeding during hospital stay, and breastfeeding knowledge were
      examined. Multivariate logistic regression analyses were performed to identify
      factors associated with initiation and continuation at 1, 6 and 12 months
      according to mothers' employment status. RESULTS: Breastfeeding initiation rates
      were similar regardless of mothers' employment status. Continuation rates
      decreased for both groups of mothers, but were significantly lower among employed
      mothers at all duration points. Unemployed mothers who were able to keep their
      babies in the same room during the hospital stay were more likely to initiate
      breastfeeding. The factor that was consistently associated with breastfeeding
      continuation for all duration points among unemployed mothers was whether the
      mother breastfed during the hospital stay. Higher knowledge scores and having an
      infant with atopic dermatitis were also associated with breastfeeding
      continuation at 6 months and 12 months, respectively for unemployed mothers, and
      receiving education on breastfeeding was associated with 12-month continuation
      for employed mothers. CONCLUSION: These results emphasize the significant roles
      of hospitals for breastfeeding initiation and continuation, with rooming-in,
      initial breastfeeding practice and education during hospital stay as important
      practices. In addition, for working mothers to continue their breastfeeding,
      significant support from the workplace is crucial.

PMID- 25947193
TI  - The confusion assessment method for the intensive care unit in patients with
      cirrhosis.
AB  - In the intensive care unit (ICU), delirium is routinely measured with the widely
      used, validated Confusion Assessment Method for the ICU (CAM-ICU), but CAM-ICU
      has not been studied in patients with cirrhosis. We studied a group of patients
      with cirrhosis to determine the relationship between delirium measured by CAM-ICU
      and clinical outcomes. Consecutive patients with cirrhosis admitted to the ICU
      from 2009 to 2012 were included in a retrospective cohort study. Patients were
      screened twice daily for coma and delirium during their ICU stay using the
      Richmond Agitation Sedation Scale (RASS) and CAM-ICU. The association between
      delirium/coma and mortality was determined using multiple logistic regression.
      RASS and CAM-ICU were also compared to a retrospective assessment of hepatic
      encephalopathy (HE). Of 91 patients with cirrhosis, 26 (28.6 %) developed
      delirium/coma. RASS/CAM-ICU had fair agreement with the HE assessment (kappa
      0.38). Patients with delirium/coma had numerically greater mortality in-hospital
      (23.1 vs. 7.7 %, p = 0.07) and at 90 days (30.8 vs. 18.5 %, p = 0.26), and they
      also had longer hospital length of stay (median 19.5 vs. 6 days, p < 0.001).
      Delirium/coma was associated with increased inpatient mortality, independent of
      disease severity (unadjusted OR 3.6; 95 % CI, 0.99-13.1; MELD-adjusted OR 5.4; 95
      % CI, 1.3-23.8; acute physiology score-adjusted OR 2.2; 95 % CI, 0.53-8.9).
      Delirium/coma was also associated with longer length of stay after adjusting for
      disease severity. In critically ill patients with cirrhosis, delirium/coma as
      measured by the RASS and CAM-ICU is associated with increased mortality and
      hospital length of stay. For these patients, these measures provide valuable
      information and may be useful tools for clinical care. RASS and CAM-ICU need to
      be compared to HE-specific measures in future studies. 

PMID- 25947194
TI  - Nanodiamonds protect skin from ultraviolet B-induced damage in mice.
AB  - BACKGROUND: Solar ultraviolet (UV) radiation causes various deleterious effects,
      and UV blockage is recommended for avoiding sunburn. Nanosized titanium dioxide
      and zinc oxide offer effective protection and enhance cosmetic appearance but
      entail health concerns regarding their photocatalytic activity, which generates
      reactive oxygen species. These concerns are absent in nanodiamonds (NDs). Among
      the UV wavelengths in sunlight, UVB irradiation primarily threatens human health.
      RESULTS: The efficacy and safety of NDs in UVB protection were evaluated using
      cell cultures and mouse models. We determined that 2 mg/cm(2) of NDs efficiently
      reduced over 95% of UVB radiation. Direct UVB exposure caused cell death of
      cultured keratinocyte, fibroblasts and skin damage in mice. By contrast, ND
      shielding significantly protected the aforementioned pathogenic alterations in
      both cell cultures and mouse models. CONCLUSIONS: NDs are feasible and safe
      materials for preventing UVB-induced skin damage.

PMID- 25947195
TI  - Ni-Vanuatu health-seeking practices for general health and childhood diarrheal
      illness: results from a qualitative methods study.
AB  - BACKGROUND: A local perspective on diarrheal illness has been shown to enhance
      control strategies for diarrheal disease in traditional rural settings. We aimed
      to assess caregivers' understandings of childhood general and diarrheal illness,
      in one rural community in Vanuatu, to help formulate control strategies for
      preventing diarrheal disease. FINDINGS: This was a descriptive study using
      qualitative analysis of responses to open-ended questions to provide a fuller
      understanding of illness. Thematic analysis with categories derived from medical
      anthropology was used to analyse responses and draw conclusions. Twenty-nine
      participants were interviewed; 22 were maternal responses, three were traditional
      practitioners, two were rural health care workers, one was a spiritual healer and
      one had a caregiver role. Respondents categorised illness as biomedical or
      traditional. Explanations of illness were enmeshed in and derived from both the
      traditional and biomedical system as the illness experience in the child under
      their care unfolded. Diarrheal severity influenced treatment selection and
      respondents expressed a preference for biomedical assistance. Respondents
      articulated a preference for biomedicine as the primary help-seeking resort for
      small children. Exclusive reliance on either traditional or biomedical options
      was uncommon. Local herbal remedies were the preferred home treatment when
      illness was known or mild, while oral rehydration therapy was used when accessing
      biomedical practitioners. CONCLUSIONS: Belief about diarrheal illness was
      influenced by traditional medicine and biomedicine. New evidence points to a
      growing preference for biomedicine as the first choice for severe childhood
      diarrheal illness. Diarrheal illness could be countered by maternal hand hygiene
      education at the medical dispensary and rural aid post.

PMID- 25947196
TI  - Elemental Bioimaging by Means of Fast Scanning Laser Ablation-Inductively Coupled
      Plasma-Mass Spectrometry.
AB  - One of the most common setups for elemental bioimaging, the hyphenation of a
      laser ablation (LA) system and an inductively coupled plasma mass spectrometer
      (ICP-MS), was expanded by adding full scan mass spectrometric information as
      another dimension of information. While most studies deal with the analysis of
      typically not more than up to 10 isotopes per scan cycle, a fast scanning
      quadrupole mass analyzer was utilized to record the full mass spectrum of
      interest in this work. Mass-to-charge ratios from 6 to 250 were observed within
      one cycle. Besides the x- and y-position on the ablated sample and the intensity,
      the m/z-ratio served as fourth variable for each pixel of the obtained data,
      closing thereby the gap between "inorganic" and "organic" mass spectrometric
      imaging techniques. The benefits of this approach include an improved control of
      interferences, the discovery of unexpected elemental distributions, the
      possibility to plot isotopic ratios, and to integrate the intensities of a
      certain number of mass channels recorded for each isotope, thus virtually
      increasing sensitivity. The respective data are presented for dried droplets as
      well as embedded animal and human tissue slices. Limits of detection were
      calculated and found to be in accordance with counting statistics. A dedicated
      software macro was developed for data manipulation prior to common evaluation and
      image creation.

PMID- 25947197
TI  - Pyroelectricity Assisted Infrared-Laser Desorption Ionization (PAI-LDI) for
      Atmospheric Pressure Mass Spectrometry.
AB  - A new atmospheric pressure ionization method termed pyroelectricity-assisted
      infrared laser desorption ionization (PAI-LDI) was developed in this study. The
      pyroelectric material served as both sample target plate and enhancing ionization
      substrate, and an IR laser with wavelength of 1064 nm was employed to realize
      direct desorption and ionization of the analytes. The mass spectra of various
      compounds obtained on pyroelectric material were compared with those of other
      substrates. For the five standard substances tested in this work, LiNbO3
      substrate produced the highest ion yield and the signal intensity was about 10
      times higher than that when copper was used as substrate. For 1-adamantylamine,
      as low as 20 pg (132.2 fmol) was successfully detected. The active ingredient in
      (Compound Paracetamol and 1-Adamantylamine Hydrochloride Capsules), 1
      adamantylamine, can be sensitively detected at an amount as low as 150 pg, when
      the medicine stock solution was diluted with urine. Monosaccharide and
      oligosaccharides in Allium Cepa L. juice was also successfully identified with
      PAI-LDI. The method did not require matrix-assisted external high voltage or
      other extra facility-assisted set-ups for desorption/ionization. This study
      suggested exciting application prospect of pyroelectric materials in matrix- and
      electricity-free atmospheric pressure mass spectrometry research.

PMID- 25947198
TI  - DCC functions as an accelerator of thalamocortical axonal growth downstream of
      spontaneous thalamic activity.
AB  - Controlling the axon growth rate is fundamental when establishing brain
      connections. Using the thalamocortical system as a model, we previously showed
      that spontaneous calcium activity influences the growth rate of thalamocortical
      axons by regulating the transcription of Robo1 through an NF-kappaB-binding site
      in its promoter. Robo1 acts as a brake on the growth of thalamocortical axons in
      vivo. Here, we have identified the Netrin-1 receptor DCC as an accelerator for
      thalamic axon growth. Dcc transcription is regulated by spontaneous calcium
      activity in thalamocortical neurons and activating DCC signaling restores normal
      axon growth in electrically silenced neurons. Moreover, we identified an AP-1
      binding site in the Dcc promoter that is crucial for the activity-dependent
      regulation of this gene. In summary, we have identified the Dcc gene as a novel
      downstream target of spontaneous calcium activity involved in axon growth.
      Together with our previous data, we demonstrate a mechanism to control axon
      growth that relies on the activity-dependent regulation of two functionally
      opposed receptors, Robo1 and DCC. These two proteins establish a tight and
      efficient means to regulate activity-guided axon growth in order to correctly
      establish neuronal connections during development. 

PMID- 25947199
TI  - Is pain better tolerated with mini-hysteroscopy than with conventional device? A
      systematic review and meta-analysis : hysteroscopy scope size and pain.
AB  - BACKGROUND: Hysteroscopy is an indispensable approach in gynecology.
      Miniaturization may reduce pain allowing office procedures without anesthesia.
      OBJECTIVES: Our main objective is to determine if modifications in scope
      diameters have made office hysteroscopy less painful. SEARCH STRATEGY: Studies
      were sought with key words "hysteroscopy" and "pain" from available online
      sources. Time frame was from 2000 onward. Thirty-three articles were retrieved
      for detailed analysis. SELECTION CRITERIA: Prospective randomized trials,
      studying pain as main outcome in office hysteroscopy expressed in means,
      confidence intervals and SD, comparing office mini-hysteroscopy to conventional
      hysteroscopy. Studies or arms within a study where conscientious sedation,
      anesthesia or non-steroidal drugs were used were excluded. DATA COLLECTION AND
      ANALYSIS: We analyzed data from eight studies (seven RCT) comparing mini
      hysteroscopy with conventional scopes, involving a total of twenty-three hundred
      and twenty-two participants, of which nineteen hundred and eighty-six completed
      the intervention. MAIN RESULTS: A meta-analysis revealed a significant reduction
      pain score (MD: -3.64; 95 % CI -5.16 to -2.12; test for overall effect p <
      0.00001) and available data support miniaturization decreases pain in outpatient
      hysteroscopy. CONCLUSIONS: Pain in office hysteroscopy is lower with mini
      hysteroscopes.

PMID- 25947200
TI  - The impact of physical fitness and body mass index in children on the development
      of acute mountain sickness: A prospective observational study.
AB  - BACKGROUND: Acute mountain sickness (AMS) is commonly found among people
      traveling above 2500 m. We investigated whether the occurrence of AMS is related
      to differences in individual physical fitness and BMI in subjects 11-13 years of
      age. METHODS: This study was conducted at Xue Mountain, Taiwan (elevation of 3886
      m) between June 13, 2011 and June 17, 2011. Subjects were asked to ascend from
      Taipei City (25 m) to the summit (3886 m) over 3 days and 2 nights. Gender, age,
      weight, height, and fitness index (determined using a 3-minute step test) were
      recorded at sea level before ascent. The Lake Louise AMS score was used to record
      symptoms and diagnose AMS. RESULTS: A total of 179 subjects (mean age: 11.8
      years; 102 males, 77 females) were included in the analysis. A total of 44.7% of
      subjects were diagnosed with AMS. Male gender (p = 0.004) and elevated body mass
      index (BMI) (p < 0.001) were each associated with the development of AMS. However
      the physical fitness index was comparable in subjects with and without AMS (67.8
      +/- 10.1 vs. 68.0 +/- 9.3, p = 0.9). CONCLUSIONS: This study shows that both BMI
      and male gender were associated with the development of AMS in 11-13 year old
      children. Physical fitness was not associated with the occurrence of AMS.

PMID- 25947201
TI  - Clinical profile of childhood-onset psoriasis and prevalence of HLA-Cw6: a
      hospital-based study from India.
AB  - BACKGROUND: Childhood-onset psoriasis (COP), a distinct clinical entity, may be
      associated with HLA-Cw6 positivity and metabolic and cardiovascular
      complications. There is some evidence that HLA-Cw6 positivity is associated with
      more extensive or severe disease and that positivity is lower in Asian patients
      than in Caucasians. We describe the clinical profile, prevalence of the HLA-Cw6
      allele, metabolic syndrome (MetS) and vitamin D deficiency in Indian patients
      with COP. METHODS: In this cross-sectional hospital-based study over 15 months
      (June 2010-August 2011), 108 consecutive patients with disease onset <=16 years
      were enrolled. Demographic, clinical and laboratory data were collected. Patients
      were categorised as children with COP (CCOP; n=69) or adults with COP (ACOP;
      n=39). Disease severity was assessed using body surface area (BSA) involved and
      Psoriasis Area and Severity Index (PASI) score. RESULTS: The most common
      morphological type was chronic plaque psoriasis; follicular psoriasis was seen
      only in children. Adults with disease onset in childhood, when compared with
      CCOP, had later disease onset (11.0+/-4.0 vs 6.9+/-3.8 (mean+/-SD) years;
      p<0.0001) of greater severity (p=0.021) based on BSA involved. PASI scores were,
      however, similar in ACOP and CCOP. Body mass index was not associated with
      disease severity. Of the 83 who underwent HLA-C typing, 46 (55.4%) were positive;
      positivity was associated with guttate lesions (p=0.031), scalp involvement
      (p=0.004), greater BSA involvement (p=0.002) and higher PASI scores (p=0.013).
      Vitamin D deficiency, obesity and MetS were present in 77.4%, 10.7% and 14.5% of
      patients, respectively. CONCLUSIONS: Among Indian patients, CCOP have earlier
      disease onset than ACOP. HLA-Cw6 was associated with guttate psoriasis, scalp
      involvement and disease severity. Vitamin D deficiency was common.

PMID- 25947202
TI  - Challenges to undertaking randomised trials with looked after children in social
      care settings.
AB  - BACKGROUND: Randomised controlled trials (RCTs) are widely viewed as the gold
      standard for assessing effectiveness in health research; however many researchers
      and practitioners believe that RCTs are inappropriate and un-doable in social
      care settings, particularly in relation to looked after children. The aim of this
      article is to describe the challenges faced in conducting a pilot study and phase
      II RCT of a peer mentoring intervention to reduce teenage pregnancy in looked
      after children in a social care setting. METHODS: Interviews were undertaken with
      social care professionals and looked after children, and a survey conducted with
      looked after children, to establish the feasibility and acceptability of the
      intervention and research design. RESULTS: Barriers to recruitment and in
      managing the intervention were identified, including social workers acting as
      informal gatekeepers; social workers concerns and misconceptions about the
      recruitment criteria and the need for and purpose of randomisation; resource
      limitations, which made it difficult to prioritise research over other demands on
      their time and difficulties in engaging and retaining looked after children in
      the study. CONCLUSIONS: The relative absence of a research infrastructure and
      culture in social care and the lack of research support funding available for
      social care agencies, compared to health organisations, has implications for
      increasing evidence-based practice in social care settings, particularly in this
      very vulnerable group of young people.

PMID- 25947204
TI  - Comment on Authenticity and traceability of vanilla flavors by analysis of stable
      isotopes of carbon and hydrogen.

PMID- 25947203
TI  - Platelet dysfunction in hypercholesterolemia mice, two Alzheimer's disease mouse
      models and in human patients with Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a severe neurodegenerative disorder characterized
      mainly by accumulation of amyloid-beta plaques and neurofibrillary tangles,
      synaptic and neuronal loss. Blood platelets contain the neurotransmitter
      serotonin and amyloid-precursor protein (APP), and may thus be useful as a
      peripheral biomarker for AD. The aim of the present study was to functionally
      characterize platelets by FACS, to examine alterations in APP expression and
      secretion, and to measure serotonin levels in hypercholesterolemia mice with AD
      like pathology and in two AD mouse models, the triple transgenic AD model (3xTg)
      and the APP overexpressing AD model with the Swedish-Dutch-Iowa mutations
      (APP_SweDI). These data are supplemented with epidermal growth factor (EGF)
      levels and compared with changes observed in platelets of patients with AD. We
      observed decreased platelet APP isoforms in 3xTg mice and patients with AD when
      analysed by means of Western blot. In patients, a significant increase of APP
      levels was observed when assessed by ELISA. Secreted APPbeta proved to be altered
      amongst all three animal models of AD at different time points and in human
      patients with AD. Serotonin levels were only reduced in 7 and 14 month old 3xTg
      mice. Moreover, we found significantly lower EGF levels in human AD patients and
      could thereby reproduce previous findings. Taken together, our data confirm that
      platelets are dysfunctional in AD, however, results from AD animal models do not
      coincide in all aspects, and markedly differ when compared to AD patients. We
      support previous data that APP, as well as EGF, could become putative biomarkers
      for diagnosing AD in human platelets.

PMID- 25947206
TI  - High-resolution X-ray absorption spectroscopy of iron carbonyl complexes.
AB  - We apply high-energy-resolution fluorescence-detected (HERFD) X-ray absorption
      near-edge spectroscopy (XANES) to study iron carbonyl complexes. Mono-, bi-, and
      tri-nuclear carbonyl complexes and pure carbonyl complexes as well as carbonyl
      complexes containing hydrocarbon ligands are considered. The HERFD-XANES spectra
      reveal multiple pre-edge peaks with individual signatures for each complex, which
      could not be detected previously with conventional XANES spectroscopy. These
      peaks are assigned and analysed with the help of TD-DFT calculations. We
      demonstrate that the pre-edge peaks can be used to distinguish the different
      types of iron-iron interactions in carbonyl complexes. This opens up new
      possibilities for applying HERFD-XANES spectroscopy to probe the electronic
      structure of iron catalysts. 

PMID- 25947205
TI  - Dramatic reduction in Clostridium difficile ribotype 027-associated mortality
      with early fecal transplantation by the nasogastric route: a preliminary report.
AB  - Clostridium difficile ribotype 027 (CD027)-associated diarrhea preferentially
      affects elderly patients and causes a high mortality rate. Fecal microbiota
      transplantation has become an alternative treatment for recurrent C. difficile
      infections. An outbreak of CD027 infections has occurred in Marseille since March
      2013. From March to November 2013, we treated patients using only antibiotics or
      fecal microbiota transplantation after at least three relapses. Beginning in
      November 2013, we performed early transplantation using a nasogastric tube during
      the first week of infection, in combination with antibiotic treatment. Sixty-one
      patients with a mean age of 84 years were hospitalized, including 42 patients
      treated only with antibiotics, three with tardive transplantation, and 16 with
      early transplantation. The patients were comparable in clinical involvement. The
      global mortality rate was 3/16 (18.75 %) among the patients treated by early
      transplantation and 29/45 (64.4 %) among the patients only treated by antibiotics
      or by tardive transplantation (p < 0.01). Among these 45 patients, 23 (51 %) died
      at day 31, including 17 who died at day 7. Early fecal transplantation was
      associated with a significantly reduced mortality rate, with only one patient
      dead at day 31 (6.25 %). In a Cox model, early transplantation was the only
      independent predictor of survival (hazard ratio 0.18, 95 % confidence interval
      0.05-0.61, p = 0.006). Six of the 16 patients (37.5 %) needed a second
      transplantation before symptom resolution. Early fecal microbiota transplantation
      in combination with antibiotics should be the first-line treatment for CD027
      infections. 

PMID- 25947207
TI  - Removal of polycyclic aromatic hydrocarbons from sediments using sodium
      persulfate activated by temperature and nanoscale zero-valent iron.
AB  - The oxidation of 16 polycyclic aromatic hydrocarbons (PAHs) compounds in
      sediments by sodium persulfate (Na2S2O8) simultaneously activated by temperature
      and nano zero-valent iron (nZVI) as the source of catalytic ferrous iron was
      investigated. The effect of various controlling factors, including S2O8(2-)
      (0.017-170 g/L), nZVI (0.01-1 g/L), and temperature (50-70  degrees C) were
      performed. The efficiency to remove PAHs was 10.7-39.1% for unactivated
      persulfate. The treated sample had over 50% of the persulfate still remaining
      from an initial persulfate dose of 170 g/L, whereas less than 1% of the
      persulfate remained from an initial persulfate dose of 0.017, 0.17, and 1.7 g/L.
      Adequate persulfate (170 g/L) must be present because it is the source of the
      sulfate radicals responsible for the degradation of PAHs. Results indicated that
      increasing temperature and the addition of nZVI into a persulfate-slurry system
      could enhance the persulfate oxidation process. The best removal efficiency (90%)
      was achieved after 24 hr while adding nZVI (0.01 g/L) to persulfate (170 g/L) at
      temperature of 70  degrees C. The results suggested that nZVI assisted persulfate
      oxidation without elevating temperature may be a suitable and economic
      alternative for the ex situ treatment of PAH-contaminated sediments.
      IMPLICATIONS: Nano zero-valent iron (nZVI) has been successfully applied to
      transform/degrade contaminants in soils and water. Additionally, nZVI has been
      used as a catalyst to activate persulfate for the treatment of various
      contaminants. In this study, with the support of temperature, nZVI-persulfate
      oxidation system for treatment of PAH-contaminated sediments was improved
      significantly and the treated sediment could meet remediation goals.

PMID- 25947208
TI  - A methodology to estimate uncertainty for emission projections through
      sensitivity analysis.
AB  - Air pollution abatement policies must be based on quantitative information on
      current and future emissions of pollutants. As emission projections uncertainties
      are inevitable and traditional statistical treatments of uncertainty are highly
      time/resources consuming, a simplified methodology for nonstatistical uncertainty
      estimation based on sensitivity analysis is presented in this work. The
      methodology was applied to the "with measures" scenario for Spain, concretely
      over the 12 highest emitting sectors regarding greenhouse gas and air pollutants
      emissions. Examples of methodology application for two important sectors (power
      plants, and agriculture and livestock) are shown and explained in depth.
      Uncertainty bands were obtained up to 2020 by modifying the driving factors of
      the 12 selected sectors and the methodology was tested against a recomputed
      emission trend in a low economic-growth perspective and official figures for
      2010, showing a very good performance. IMPLICATIONS: A solid understanding and
      quantification of uncertainties related to atmospheric emission inventories and
      projections provide useful information for policy negotiations. However, as many
      of those uncertainties are irreducible, there is an interest on how they could be
      managed in order to derive robust policy conclusions. Taking this into account, a
      method developed to use sensitivity analysis as a source of information to derive
      nonstatistical uncertainty bands for emission projections is presented and
      applied to Spain. This method simplifies uncertainty assessment and allows other
      countries to take advantage of their sensitivity analyses.

PMID- 25947209
TI  - Accuracy of vertical radial plume mapping technique in measuring lagoon gas
      emissions.
AB  - Recently, the U.S. Environmental Protection Agency (EPA) posted a ground-based
      optical remote sensing method on its Web site called Other Test Method (OTM) 10
      for measuring fugitive gas emission flux from area sources such as closed
      landfills. The OTM 10 utilizes the vertical radial plume mapping (VRPM) technique
      to calculate fugitive gas emission mass rates based on measured wind speed
      profiles and path-integrated gas concentrations (PICs). This study evaluates the
      accuracy of the VRPM technique in measuring gas emission from animal waste
      treatment lagoons. A field trial was designed to evaluate the accuracy of the
      VRPM technique. Control releases of methane (CH4) were made from a 45 m*45 m
      floating perforated pipe network located on an irrigation pond that resembled
      typical treatment lagoon environments. The accuracy of the VRPM technique was
      expressed by the ratio of the calculated emission rates (QVRPM) to actual
      emission rates (Q). Under an ideal condition of having mean wind directions
      mostly normal to a downwind vertical plane, the average VRPM accuracy was 0.77+/
      0.32. However, when mean wind direction was mostly not normal to the downwind
      vertical plane, the emission plume was not adequately captured resulting in lower
      accuracies. The accuracies of these nonideal wind conditions could be
      significantly improved if we relaxed the VRPM wind direction criteria and
      combined the emission rates determined from two adjacent downwind vertical planes
      surrounding the lagoon. With this modification, the VRPM accuracy improved to
      0.97+/-0.44, whereas the number of valid data sets also increased from 113 to
      186. IMPLICATIONS: The need for developing accurate and feasible measuring
      techniques for fugitive gas emission from animal waste lagoons is vital for
      livestock gas inventories and implementation of mitigation strategies. This field
      lagoon gas emission study demonstrated that the EPA's vertical radial plume
      mapping (VRPM) technique can be used to accurately measure lagoon gas emission
      with two downwind vertical concentration planes surrounding the lagoon.

PMID- 25947210
TI  - Mobile measurements of climate forcing agents: Application to methane emissions
      from landfill and natural gas compression.
AB  - Measuring greenhouse gas (GHG) source emissions provides data for validation of
      GHG inventories, which provide the foundation for climate change mitigation. Two
      Toyota RAV4 electric vehicles were outfitted with high-precision instrumentation
      to determine spatial and temporal resolution of GHGs (e.g., nitrous oxide,
      methane [CH4], and carbon dioxide [CO2]), and other gaseous species and
      particulate metrics found near emission sources. Mobile measurement platform
      (MMP) analytical performance was determined over relevant measurement time
      scales. Pollutant residence times through the sampling configuration were
      measured, ranging from 3 to 11 sec, enabling proper time alignment for spatial
      measurement of each respective analyte. Linear response range for GHG analytes
      was assessed across expected mixing ratio ranges, showing minimal regression and
      standard error differences between 5, 10, 30, and 60 sec sampling intervals and
      negligible differences between the two MMPs. GHG instrument drift shows deviation
      of less than 0.8% over a 24-hr measurement period. These MMPs were utilized in
      tracer-dilution experiments at a California landfill and natural gas compressor
      station (NGCS) to quantify CH4 emissions. Replicate landfill measurements during
      October 2009 yielded annual CH4 emissions estimates of 0.10+/-0.01, 0.11+/-0.01,
      and 0.12+/-0.02 million tonnes of CO2 equivalent (MTCO2E). These values compare
      favorably to California GHG Emissions Inventory figures for 2007, 2008, and 2009
      of 0.123, 0.125, and 0.126 MTCO2E/yr, respectively, for this facility.
      Measurements to quantify NGCS boosting facility-wide emissions, during June 2010
      yielded an equivalent of 5400+/-100 TCO2E/yr under steady-state operation.
      However, measurements during condensate transfer without operational vapor
      recovery yield an instantaneous emission rate of 2-4 times greater, but was
      estimated to only add 12 TCO2E/yr overall. This work displays the utility for
      mobile GHG measurements to validate existing measurement and modeling approaches,
      so emission inventory values can be confirmed and associated uncertainties
      reduced. IMPLICATIONS: Measuring greenhouse gas (GHG) source emissions provides
      data and validation for GHG inventories, the foundation for climate change
      mitigation. Mobile measurement platforms with robust analytical instrumentation
      completed tracer-dilution experiments in California at a landfill and natural gas
      compressor station (NGCS) to quantify CH4 emissions. Data collected for landfill
      CH4 agree with the current California emissions inventory, while NGCS data show
      the possible variability from this type of facility. This work displays the
      utility of mobile GHG measurements to validate existing measurement and modeling
      approaches, such that emission inventory values can be confirmed, associated
      uncertainties reduced, and mitigation efforts quantified.

PMID- 25947211
TI  - Low-nitrogen oxides combustion of dried sludge using a pilot-scale cyclone
      combustor with recirculation.
AB  - Recently, numerical and experimental studies have been conducted to develop a
      moderate or intense low-oxygen dilution (MILD) combustion technology for solid
      fuels. The study results demonstrated that intense recirculation inside the
      furnace by high-momentum air is a key parameter to achieve the MILD combustion of
      solid fuels. However, the high-velocity air requires a significant amount of
      electricity consumption. A cyclone-type MILD combustor was therefore designed and
      constructed in the authors' laboratory to improve the recirculation inside the
      combustor. The laboratory-scale tests yielded promising results for the MILD
      combustion of dried sewage sludge. To achieve pilot-scale MILD combustion of
      dried sludge in this study, the effects of geometric parameters such as the
      venturi tube configuration, the air injection location, and the air nozzle
      diameter were investigated. With the optimized geometric and operational
      conditions, the pilot-scale cyclone combustor demonstrated successful MILD
      combustion of dried sludge at a rate of 75 kg/hr with an excess air ratio of
      1.05. IMPLICATIONS: A horizontal cyclone combustor with recirculation
      demonstrated moderate or intense low-oxygen dilution (MILD) combustion of dried
      sewage sludge at a rate of 75 kg/hr. Optimizing only geometric and operational
      conditions of the combustor reduced nitrogen oxide (NOx) emissions to less than
      75 ppm. Because the operating cost of the MILD combustor is much lower than that
      of the selective catalytic reduction (SCR) applied to the conventional combustor,
      MILD combustion technology with the cyclone type furnace is an eligible option
      for reducing NOx emissions from the combustion of dried sewage sludge.

PMID- 25947212
TI  - Measurement of fine particulate matter water-soluble inorganic species and
      precursor gases in the Alberta Oil Sands Region using an improved semicontinuous
      monitor.
AB  - The ambient ion monitor-ion chromatography (AIM-IC) system, which provides hourly
      measurements of the main chemical components of PM2.5 (particulate matter with an
      aerodynamic diameter<2.5 MUm) and its precursor gases, was evaluated and deployed
      from May to July 2011 and April to December 2013 in the Athabasca Oil Sands
      Region (AOSR) of northeastern Alberta, Canada. The collection efficiencies for
      the gas-phase SO2 and HNO3 using the cellulose membrane were 96% and 100%,
      respectively, and the collection efficiency of NH3 using the nylon membrane was
      100%. The AIM-IC was compared with a collocated annular denuder sampling system
      (ADSS) and a Federal Reference Method (FRM) Partisol PM2.5 sampler. The
      correlation coefficients of SO4(2-) concentrations between the AIM-IC and ADSS
      and between the AIM-IC and the Partisol PM2.5 sampler were 0.98 and 0.95,
      respectively. The comparisons also showed no statistically significant difference
      between the measurement sets, suggesting that the AIM-IC measurements of the
      PM2.5 chemical composition are comparable to the ADSS and Partisol PM2.5 methods.
      NH3 concentration in the summer (mean+/-standard deviation, 1.9+/-0.7 ug m(-3))
      was higher than in the winter (1.3+/-0.9 ug m(-3)). HNO3 and NO3- concentrations
      were generally low in the AOSR, and especially in the winter months. NH4+ (0.94+/
      0.96 ug m(-3)) and SO4(2-) (0.58+/-0.93 ug m(-3)) were the major ionic species of
      PM2.5. Direct SO2 emissions from oil sands processing operations influenced
      ambient particulate NH4+ and SO4(2-) values, with hourly concentrations of NH4+
      and SO4(2-) measured downwind (~30 km away from the stack) at 10 and 28 ug m(-3).
      During the regional forest fire event in 2011, high concentrations of NO3-, NH4+,
      HNO3, NH3, and PM2.5 were observed and the corresponding maximum hourly
      concentrations were 31, 15, 9.6, 89, and >450 (the upper limit of PM2.5
      measurement) ug m(-3), suggesting the formation of NH4NO3. IMPLICATIONS: The AOSR
      in Canada is one of the most scrutinized industrial regions in the developed
      world due to the extent of oil extraction activities. Because of this, it is
      important to accurately assess the effect of these operations on regional air
      quality. In this study, we compare a new analytical approach, AIM-IC, with more
      standard analytical approaches to understand how local anthropogenic and
      nonanthropogenic sources (e.g., forest fires) impact regional air quality. With
      this approach, we also better characterize PM2.5 composition and its precursor
      gases to understand secondary aerosol formation mechanisms and to better identify
      possible control techniques if needed.

PMID- 25947213
TI  - Effects of fine particles on children's hospital admissions for respiratory
      health in Seville, Spain.
AB  - This study analyzes the influence of fine particles PM2.5 on nonprogrammed
      children's hospital admissions that occurred in the city of Seville between 2007
      and 2011, and makes an economic assessment of the cost of the children's hospital
      admissions for respiratory causes due to particle pollution. The PM2.5 dose
      response functions for each type of hospital admission were used to quantify the
      cost of the hospital admissions. It can be concluded that the PM2.5
      concentrations have negative effects on bronchiolitis, pneumonia, asthma, and
      bronchitis and other causes. A reduction of the daily average annual PM2.5
      concentration from the existing levels to 10 ug/m3 would show an annual average
      reduction of children's hospital admissions due to respiratory diseases of 0.09
      cases. This paper shows that the daily average cost for children hospital
      admissions due to respiratory reasons in the city of Seville, associated with
      daily average annual levels of PM2.5 above 10 ug/m3, was almost 200?.
      IMPLICATIONS: Elevated PM2.5 concentrations in Seville have negative effects on
      children's bronchiolitis, pneumonia, asthma, and bronchitis and other causes. A
      reduction of the daily average annual PM2.5 concentration from the existing
      levels to 10 MUg/m3 would suppose an annual mean reduction of children's hospital
      admissions due to respiratory diseases of 0.09 cases.

PMID- 25947214
TI  - Chemical characteristics of long-range-transported fine particulate matter at
      Gosan, Jeju Island, in the spring and fall of 2008, 2009, 2011, and 2012.
AB  - Carbonaceous species (organic carbon [OC] and elemental carbon [EC]) and
      inorganic ions of particulate matter less than 2.5 MUm (PM2.5) were measured to
      investigate the chemical characteristics of long-range-transported (LTP) PM2.5 at
      Gosan, Jeju Island, in Korea in the spring and fall of 2008-2012 (excluding
      2010). On average, the non-sea-salt (nss) sulfate (4.2 ug/m3) was the most
      dominant species in the spring, followed by OC (2.6 ug/m3), nitrate (2.1 ug/m3),
      ammonium (1.7 ug/m3), and EC (0.6 ug/m3). In the fall, the nss-sulfate (4.7
      ug/m3) was also the most dominant species, followed by OC (4.0 ug/m3), ammonium
      (1.7 ug/m3), nitrate (1.1 ug/m3), and EC (0.7 ug/m3). Both sulfate and OC were
      higher in the fall than in the spring, possibly due to more common northwest air
      masses (i.e., coming from China and Korea polluted areas) and more frequent
      biomass burnings in the fall. There was no clear difference in the EC between the
      spring and fall. The correlation between OC and EC was not strong; thus, the OC
      measured at Gosan was likely transported across a long distance and was not
      necessarily produced in a manner similar to the EC. Distinct types of LTP events
      (i.e., sulfate-dominant LTP versus OC-dominant LTP) were observed. In the sulfate
      dominant LTP events, air masses directly arrived at Gosan without passing over
      the Korean Peninsula from the industrial area of China within 48 hr. During these
      events, the aerosol optical depth (AOD) increased to 1.63. Ionic balance data
      suggest that the long-range transported aerosols are acidic. In the OC-dominant
      LTP event, a higher residence time of air masses in Korea was observed (the air
      masses departing from the mainland of China arrived at the sampling site after
      passing Korea within 60-80 hr). IMPLICATIONS: In Northeast Asia, various natural
      and anthropogenic sources contribute to the complex chemical components and
      affect local/regional air quality and climate change. Chemical characteristics of
      long-range-transported (LTP) PM2.5 were investigated during spring and fall of
      2008, 2009, 2011, and 2012. Based on air mass types, sulfate-dominant LTP and OC
      dominant LTP were observed. A long-term variation and chemical characteristics of
      PM2.5 along with air mass and satellite data are required to better understand
      long-range-transported aerosols.

PMID- 25947216
TI  - Assessment of microbial contamination within working environments of different
      types of composting plants.
AB  - The objective of the study was to determine the degree of microbiological
      contamination, type of microflora, bioaerosol particle size distribution, and
      concentration of endotoxins in dust in different types of composting plants. In
      addition, this study provides a list of indicator microorganisms that pose a
      biological threat in composting facilities, based on their prevalence within the
      workplace, source of isolation, and health hazards. We undertook microbiological
      analysis of the air, work surfaces, and compost, and assessed the particle size
      distribution of bioaerosols using a six-stage Andersen sampler. Endotoxins were
      determined using gas chromatography-mass spectrometry (GC-MS). Microbial
      identification was undertaken both microscopically and using biochemical tests.
      The predominant bacterial and fungal species were identified using 16S rRNA and
      ITS1/2 analysis, respectively. The number of mesophilic microorganisms in
      composting plants amounted to 6.9*10(2)-2.5*10(4) CFU/m3 in the air, 2.9*10(2)
      3.3*10(3) CFU/100 cm2 on surfaces, and 2.2*10(5)-2.4*10(7) CFU/g in compost.
      Qualitative analysis revealed 75 microbial strains in composting plants, with
      filamentous fungi being the largest group of microorganisms, accounting for as
      many as 38 isolates. The total amount of endotoxins was 0.0062-0.0140 nmol/mg of
      dust. The dust fraction with aerodynamic particle diameter of 0.65-1.1 MUm
      accounted for 28-39% of bacterial aerosols and 4-13% of fungal aerosols. We
      propose the following strains as indicators of harmful biological agent
      contamination: Bacillus cereus, Aspergillus fumigatus, Cladosporium
      cladosporioides, C. herbarum, Mucor hiemalis, and Rhizopus oryzae for both types
      of composting plants, and Bacillus pumilus, Mucor fragilis, Penicillium
      svalbardense, and P. crustosum for green waste composting plants. The biological
      hazards posed within these plants are due to the presence of potentially
      pathogenic microorganisms and the inhalation of respirable bioaerosol. Depending
      on the type of microorganism, these hazards may be aggravated or reduced after
      cleaning procedures. IMPLICATIONS: This study assessed the microbial
      contamination in two categories of composting plants: (1) facilities producing
      substrates for industrial cultivation of button mushrooms, and (2) facilities for
      processing biodegradable waste. Both workplaces showed potentially pathogenic
      microorganisms, respirable bioaerosol, and endotoxin. These results are useful to
      determine the procedures to control harmful biological agents, and to disinfect
      workplaces in composting plants.

PMID- 25947215
TI  - Elemental mercury oxidation in an electrostatic precipitator enhanced with in
      situ soft X-ray irradiation.
AB  - Corona discharge based techniques are promising approaches for oxidizing
      elemental mercury (Hg0) in flue gas from coal combustion. In this study, in-situ
      soft X-rays were coupled to a DC (direct current) corona-based electrostatic
      precipitator (ESP). The soft X-rays significantly enhanced Hg0 oxidation, due to
      generation of electrons from photoionization of gas molecules and the ESP
      electrodes. This coupling technique worked better in the positive corona
      discharge mode because more electrons were in the high energy region near the
      electrode. Detailed mechanisms of Hg0 oxidation are proposed and discussed based
      on ozone generation measurements and Hg0 oxidation behavior observations in
      single gas environments (O2, N2, and CO2). The effect of O2 concentration in flue
      gas, as well as the effects of particles (SiO2, TiO2, and KI) was also evaluated.
      In addition, the performance of a soft X-rays coupled ESP in Hg0 oxidations was
      investigated in a lab-scale coal combustion system. With the ESP voltage at +10
      kV, soft X-ray enhancement, and KI addition, mercury oxidation was maximized.
      IMPLICATIONS: Mercury is a significant-impact atmospheric pollutant due to its
      toxicity. Coal-fired power plants are the primary emission sources of
      anthropogenic releases of mercury; hence, mercury emission control from coal
      fired power plant is important. This study provides an alternative mercury
      control technology for coal-fired power plants. The proposed electrostatic
      precipitator with in situ soft X-rays has high efficiency on elemental mercury
      conversion. Effects of flue gas conditions (gas compositions, particles, etc.) on
      performance of this technology were also evaluated, which provided guidance on
      the application of the technology for coal-fired power plant mercury control.

PMID- 25947217
TI  - The contribution of biowaste disposal to odor emission from landfills.
AB  - The biowaste fractions in municipal solid waste (MSW) are the main odor sources
      in landfill and cause widespread complaints from residents. The ammonia (NH3) and
      hydrogen sulfide (H2S) generation processes were simulated and compared between
      four typical biowaste fractions individually and combined in the mixed MSW. Food
      waste was found to be the main contributor to odor emission in mixed MSW, with
      H2S generation potential of 48.4 MUg kg(-1) and NH3 generation potential of 4742
      MUg kg(-1). Fruit waste was another source for NH3 generation, with 3933 MUg kg(
      1) NH3 generation potential. Meanwhile, nitrogen (N) was released in a faster way
      than sulfur (S) in waste, since 31% and 46% of total NH3 and H2S were generated
      in the first 90 days after disposal, with 1811 and 72 MUg kg(-1), and more
      emphasis should be placed in this initial period. IMPLICATIONS: Monitoring of
      odor generation from biowastes in MSW on a laboratory scale showed that food
      waste is the main source for NH3 and H2S generation, whereas waste fruit is
      another main contributor for NH3 released. Generally, N was released in a faster
      way than S from mixed-waste landfilling.

PMID- 25947218
TI  - Hybrid selective noncatalytic reduction (SNCR)/selective catalytic reduction
      (SCR) for NOx removal using low-temperature SCR with Mn-V2O5/TiO2 catalyst.
AB  - A hybrid selective noncatalytic reduction/selective catalytic reduction
      (SNCR/SCR) system that uses two types of technology, low-temperature SCR process
      and SNCR process, was designed to develop nitrogen oxide (NOx) reduction
      technology. SCR was conducted with space velocity (SV)=2400 hr(-1) and hybrid
      SNCR/SCR with SV=6000 hr(-1), since the study focused on reducing the amount of
      catalyst and both achieved 98% NOx reduction efficiency. Characteristics of NOx
      reduction by NH3 were studied for low-temperature SCR system at 150  degrees C
      using Mn-V2O5/TiO2 catalyst. Mn-added V2O5/TiO2 catalyst was produced, and
      selective catalyst reduction of NOx by NH3 was experimented. NOx reduction rate
      according to added Mn content in Mn-V2O5/TiO2 catalyst was studied with varying
      conditions of reaction temperature, normalized stoichiometric ratio (NSR), SV,
      and O2 concentration. In the catalyst experiment according to V2O5 concentration,
      1 wt.% V2O5 catalyst showed the highest NOx reduction rate: 98% reduction at
      temperature window of 200~250  degrees C. As a promoter of the V2O5 catalyst, 5
      wt.% Mn was added, and the catalyst showed 47~90% higher efficiency even with low
      temperatures, 100~200  degrees C. Mn-V2O5/TiO2 catalyst, prepared by adding 5
      wt.% Mn in V2O5/TiO2 catalyst, showed increments of catalyst activation at 150 
      degrees C as well as NOx reduction. Mn-V2O5/TiO2 catalyst showed 8% higher rate
      for NOx reduction compared with V2O5/TiO2 catalyst in 150  degrees C SCR. Thus,
      (5 wt.%)Mn-(1 wt.%)V2O5/TiO2 catalyst was applied in SCR of hybrid SNCR/SCR
      system of low temperature at 150  degrees C. Low-temperature SCR hybrid SNCR/SCR
      (150  degrees C) system and hybrid SNCR/SCR (350  degrees C) showed 91~95% total
      reduction rate with conditions of SV=2400~6000 hr(-1) SCR and 850~1050  degrees C
      SNCR, NSR=1.5~2.0, and 5% O2. Hybrid SNCR/SCR (150  degrees C) system proved to
      be more effective than the hybrid SNCR/SCR (350  degrees C) system at low
      temperature. IMPLICATIONS: NOx control is very important, since they are the part
      of greenhouse gases as well as the cause of acid rain and ozone hole. A
      technology, so-called hybrid SNCR/SCR process, was tested using Mn-V2O5/TiO2
      monolithic catalyst for NOx reduction, and the method is promising. The results
      of this study would provide some ideas to parties such as policy makers,
      environmental engineers, and so on.

PMID- 25947219
TI  - Characteristics of particulate matter emissions from toy cars with electric
      motors.
AB  - Aerosol emissions from toy cars with electric motors were characterized. Particle
      emission rates from the toy cars, as high as 7.47*10(7) particles/s, were
      measured. This emission rate is lower than other indoor sources such as smoking
      and cooking. The particles emitted from toy cars are generated from spark
      discharges inside the electric motors that power the toy cars. Size distribution
      measurements indicated that most particles were below 100 nm in diameter. Copper
      was the dominant inorganic species in these particles. By deploying aerosol mass
      spectrometers, high concentrations of particulate organic matter were also
      detected and characterized in detail. Several organic compounds were identified
      using a thermal desorption aerosol gas chromatography. The mass size distribution
      of particulate organic matter was bimodal. The formation mechanism of particulate
      organic matter from toy cars was elucidated. IMPLICATIONS: A possible new source
      of indoor air pollution, particles from electric motors in toy cars, was
      identified. This study characterized aerosol emissions from toy cars in detail.
      Most of these particles have a diameter less than 100 nm. Copper and some
      organics are the major components of these particles. Conditions that minimize
      these emissions were determined.

PMID- 25947220
TI  - Diurnal and seasonal variations of carbonyls and their effect on ozone
      concentrations in the atmosphere of Monterrey, Mexico.
AB  - Few studies have been made regarding carbonyl concentrations in Monterrey,
      Mexico. The Monterrey Metropolitan Area (MMA) has the third largest population in
      the country and has increasing pollution issues. The concentrations of 10
      aldehydes and two ketones were measured in the MMA, in the spring and fall of
      2011 and 2012. Formaldehyde (16-42 ppbv) was the most abundant carbonyl, followed
      by acetaldehyde (5-15 ppbv) and acetone (7-15 ppbv). The concentrations showed
      marked diurnal trends with maximum values between 10:00 a.m. and 2:00 p.m., when
      photochemical activity is intense. Thus, secondary production of carbonyls is
      statistically significant in the city. Biogenic production of several carbonyls,
      such as 2-butanone, was supported by their mid correlation with solar radiation
      and low correlation with propionaldehyde, which is mainly emitted by
      anthropogenic sources. The seasonal variability of the concentrations was
      observed in the first three samplings, with the highest levels reached in the
      fall. The rainy conditions during the fourth sampling did not allow comparison.
      Carbonyl-NOx-O3 analysis was made. Results indicated a carbonyl-sensitive
      atmosphere, especially during the midday samplings of 10:00 a. m. to 2:00 p.m.
      and 2:00 p.m. and 6:00 p.m. because of the intense solar radiation during these
      periods. IMPLICATIONS: Monitoring of carbonyls in Monterrey, Mexico, was
      performed to quantify the pollutant concentration in the city's atmosphere.
      Although primary emission is significantly important, the secondary production of
      the pollutants, along with ozone production being carbonyl sensitive, indicates
      that air pollution controls must address the direct sources and the precursors of
      the pollutants to achieve air quality.

PMID- 25947221
TI  - Erratum to: Repeat Abortions in New York City, 2010.

PMID- 25947222
TI  - Directed self-assembly of cylinder-forming diblock copolymers on sparse chemical
      patterns.
AB  - Using both theory and experiment, we investigate the possibility of creating
      perfectly ordered block copolymer nanostructures on sparsely patterned
      substrates. Our study focuses on scrutinizing the appropriate pattern conditions
      to avoid undesired morphologies or defects when depositing cylinder-forming AB
      diblock copolymer thin films on the substrates which are mostly neutral with
      periodic stripe regions preferring the minority domain. By systematically
      exploring the parameter space using self-consistent field theory (SCFT), the
      optimal conditions for target phases are determined, and the effects of the
      chemical pattern period and the block copolymer film thickness on the target
      phase stability are also studied. Furthermore, as a sample experimental system,
      almost perfectly aligned polystyrene-block-poly(methyl methacrylate) (PS-b-PMMA)
      diblock copolymers are demonstrated. After the pattern transfer process, highly
      ordered Al nanodot arrays following the initial vertically aligned cylinder
      pattern are created. This systematic study demonstrates the ability to control
      the structure and the position of nanopatterns on sparse chemical patterns. 

PMID- 25947223
TI  - [Neoplasms of the disseminated neuroendocrine cell system of the gastrointestinal
      tract].
AB  - The classification of neuroendocrine neoplasms (NEN) of the gastrointestinal
      tract and also the pancreas is based on the World Health Organization (WHO)
      classification from 2010, the site-related TNM stage classification and the
      clinicopathological characterization. This allows a classification of NEN that is
      adapted to the individual patient, is of high prognostic relevance and serves the
      needs of an adequate treatment. This article summarizes the current knowledge on
      the clinical pathology of gastrointestinal NEN, in order to enable a rapid
      diagnostic orientation. 

PMID- 25947224
TI  - [New aspects of tumor pathology of the pituitary].
AB  - Pituitary adenomas have to be studied in detail for structural characteristics,
      especially regarding the degree of granulation and immunohistochemical hormone
      expression, such as growth hormone (GH), prolactin, adrenocorticotropic hormone
      (ACTH), thyroid stimulating hormone (TSH), follicle stimulating hormone (FSH),
      luteinizing hormone (LH) and proliferation markers (e.g. Ki-67 and p53) for
      correlation to clinical data and assessment of the prognosis. If histological and
      immunostaining data do not correlate to the patient data, explanations for the
      discrepancies must be found. All active adenoma types can also be present as
      inactive, so-called silent adenomas showing the same features. An increased Ki-67
      index (> 3%), significant nuclear expression of protein p53 and mitoses are
      characteristic of atypical adenomas. Up to now the biological relevance of these
      atypical adenomas, especially their role as preneoplasms for pituitary carcinomas
      has not been fully elucidated. The only proof of a pituitary carcinoma is the
      existence of metastases. Extensive local invasion and a greatly increased Ki-67
      index are not sufficient for this diagnosis. Craniopharyngiomas have to be
      classified into adamantinomatous types (intrasellar and suprasellar) and
      papillary types (only suprasellar). Regressive changes are found in
      adamantinomatous types only. Strong regression may lead to difficulties in the
      differential diagnosis of Rathke's cleft cysts with squamous metaplasia.
      Demonstration of nuclear expression of beta-catenin in these cases enables the
      diagnosis of craniopharyngioma. Papillary craniopharyngiomas are characterized by
      BRAF mutations that may be helpful in the differential diagnosis. All
      pituicytomas of the neurohypophysis, all spindle cell oncocytomas of the anterior
      pituitary and all granular cell tumors of the posterior pituitary express thyroid
      transcription factor 1 (TTF-1) and are thought to be variants of a common uniform
      spindle cell tumor of the pituitary.

PMID- 25947226
TI  - A molecular epidemiological survey of Babesia, Hepatozoon, Ehrlichia and
      Anaplasma infections of dogs in Japan.
AB  - Tick-borne diseases are often encountered in canine clinical practice. In the
      present study, a molecular epidemiological survey of dogs in Japan was conducted
      to understand the prevalence and geographical distribution of Babesia spp.,
      Hepatozoon spp., Ehrlichia spp. and Anaplasma spp. Pathogen-derived DNA in blood
      samples obtained from 722 dogs with a history of exposure to ticks and/or fleas
      was examined by PCR. The prevalence of Babesia gibsoni, Babesia odocoilei-like
      species, Hepatozoon canis and Ehrlichia spp./Anaplasma spp. was 2.4% (16/722),
      0.1% (1/722), 2.5% (18/722) and 1.5% (11/722), respectively. While B. gibsoni and
      Ehrlichia spp./Anaplasma spp. were detected in the western part of Japan, H.
      canis was detected in Tohoku area in addition to western and central parts of
      Japan. 

PMID- 25947225
TI  - Gender, ageing and carework in East and Southern Africa: A review.
AB  - An estimated 58 million persons aged 60-plus live in sub-Saharan Africa; by 2050
      that number will rise sharply to 215 million. Older Africans traditionally get
      care in their old age from the middle generation. But in East and Southern
      Africa, HIV has hollowed out that generation, leaving many older persons to
      provide care for their children's children without someone to care for him or
      herself in old age. Simultaneously, the burden of disease among older persons is
      changing in this region. The result is a growing care deficit. This article
      examines the existing literature on care for and by older persons in this region,
      highlighting understudied aspects of older persons' experiences of ageing and
      care--including the positive impacts of carework, variation in the region and the
      role of resilience and pensions. We advance a conceptual framework of gendered
      identities--for both men and women--and intergenerational social exchange to help
      focus and understand the complex interdependent relationships around carework,
      which are paramount in addressing the needs of older persons in the current care
      deficit in this region, and the Global South more generally.

PMID- 25947227
TI  - Detection of the nonsense mutation of OPA3 gene in Holstein Friesian cattle with
      dilated cardiomyopathy in Japan.
AB  - Bovine dilated cardiomyopathy (DCM) is an autosomal recessive genetic disorder
      causing congestive heart failure and subsequent death. Recently, a nonsense
      mutation c.343C>T in the bovine optic atrophy 3 (OPA3) gene had been reported to
      cause the DCM in Holstein cattle in Switzerland. However, the mutation has not
      been confirmed in bovine DCM outside Switzerland. Nine Holstein Friesian cows
      that were macroscopically and histologically diagnosed with or suspected of DCM
      and 12 control cows kept in Japan were tested for the mutation. The mutation
      surrounding OPA3 DNA fragment was amplified by PCR and subjected to direct
      sequences. The homogeneous c.343C>T mutation was proved to occur in all the
      affected cows and not in the control cows. The present study is the first report
      of the mutation in the DCM affected cows outside Switzerland. 

PMID- 25947230
TI  - Non-condom related strategies to reduce the risk of HIV transmission:
      Perspectives and experiences of gay men with diagnosed HIV.
AB  - Gay men with diagnosed HIV can adopt a number of strategies to reduce the risk of
      transmitting HIV to others, although research has typically focussed on condom
      use. Interviews with 42 HIV-positive gay men who reported recent engagement in
      anal intercourse without condoms explored their awareness of sexual risk and
      their perceptions of non-condom-related strategies to reduce it. In articulating
      men's ambivalence for strategies that can only reduce the risk of transmission,
      rather than eliminating, the findings have implications for the consideration and
      integration of new biomedical interventions to reduce the likelihood of HIV
      transmission.

PMID- 25947228
TI  - Protist predation can select for bacteria with lowered susceptibility to
      infection by lytic phages.
AB  - BACKGROUND: Consumer-resource interactions constitute one of the most common
      types of interspecific antagonistic interaction. In natural communities, complex
      species interactions are likely to affect the outcomes of reciprocal co-evolution
      between consumers and their resource species. Individuals face multiple enemies
      simultaneously, and consequently they need to adapt to several different types of
      enemy pressures. In this study, we assessed how protist predation affects the
      susceptibility of bacterial populations to infection by viral parasites, and
      whether there is an associated cost of defence on the competitive ability of the
      bacteria. As a study system we used Serratia marcescens and its lytic
      bacteriophage, along with two bacteriovorous protists with distinct feeding
      modes: Tetrahymena thermophila (particle feeder) and Acanthamoeba castellanii
      (surface feeder). The results were further confirmed with another study system
      with Pseudomonas and Tetrahymena thermophila. RESULTS: We found that selection by
      protist predators lowered the susceptibility to infections by lytic phages in
      Serratia and Pseudomonas. In Serratia, concurrent selection by phages and
      protists led to lowered susceptibility to phage infections and this effect was
      independent from whether the bacteria shared a co-evolutionary history with the
      phage population or not. Bacteria that had evolved with phages were overall more
      susceptible to phage infection (compared to bacteria with history with multiple
      enemies) but they were less vulnerable to the phages they had co-evolved with
      than ancestral phages. Selection by bacterial enemies was costly in general and
      was seen as a lowered fitness in absence of phages, measured as a biomass yield.
      CONCLUSIONS: Our results show the significance of multiple species interactions
      on pairwise consumer-resource interaction, and suggest potential overlap in
      defending against predatory and parasitic enemies in microbial consumer-resource
      communities. Ultimately, our results could have larger scale effects on eco
      evolutionary community dynamics.

PMID- 25947231
TI  - 'I Once Stared at Myself in the Mirror for Eleven Hours.' Exploring mirror gazing
      in participants with body dysmorphic disorder.
AB  - This study provides insight into the lived experience of mirror gazing using
      Interpretative Phenomenological Analysis and Photo Elicitation. A total of 10
      participants who identified themselves as suffering from body dysmorphic disorder
      took photographs that related to their body dysmorphic disorder experience.
      Photographs were discussed in interviews. It was found that mirror gazing in body
      dysmorphic disorder is an embodied phenomenon. Motivations for mirror gazing were
      confusing, complex and masochistic. Overall, participants described mirrors as
      being controlling, imprisoning and disempowering forces that had a crippling and
      paralysing effect on life. It is argued that health psychologists must ask
      clients about their embodied experiences when looking in the mirror.

PMID- 25947229
TI  - HIV-1 immune activation induces Siglec-1 expression and enhances viral trans
      infection in blood and tissue myeloid cells.
AB  - BACKGROUND: Myeloid cells are key players in the recognition and response of the
      host against invading viruses. Paradoxically, upon HIV-1 infection, myeloid cells
      might also promote viral pathogenesis through trans-infection, a mechanism that
      promotes HIV-1 transmission to target cells via viral capture and storage. The
      receptor Siglec-1 (CD169) potently enhances HIV-1 trans-infection and is
      regulated by immune activating signals present throughout the course of HIV-1
      infection, such as interferon alpha (IFNalpha). RESULTS: Here we show that
      IFNalpha-activated dendritic cells, monocytes and macrophages have an enhanced
      ability to capture and trans-infect HIV-1 via Siglec-1 recognition of viral
      membrane gangliosides. Monocytes from untreated HIV-1-infected individuals trans
      infect HIV-1 via Siglec-1, but this capacity diminishes after effective
      antiretroviral treatment. Furthermore, Siglec-1 is expressed on myeloid cells
      residing in lymphoid tissues, where it can mediate viral trans-infection.
      CONCLUSIONS: Siglec-1 on myeloid cells could fuel novel CD4(+) T-cell infections
      and contribute to HIV-1 dissemination in vivo.

PMID- 25947232
TI  - Monolayer protected gold nanoparticles with metal-ion binding sites: functional
      systems for chemosensing applications.
AB  - In this review we describe the use of monolayer protected gold nanoparticles (Au
      NPs) for chemosensing applications. The attention is focused on a special
      subclass of Au NPs, namely those that contain binding sites for metal ions in the
      monolayer. It will be shown that these systems are very well-equipped for metal
      ion sensing as the complexation of the metal ions can affect the properties of
      the system in many ways leading to detectable output signals even at very low
      analyte concentrations. In addition, the presence of metal ions in the monolayer
      themselves can serve as recognition units for the highly selective interaction
      with small organic molecules or biomacromolecules. Key examples will be discussed
      that underscore the attractive properties and potential of this class of Au NPs
      as components of chemosensing assays. 

PMID- 25947234
TI  - A Neural Substrate for Rapid Timbre Recognition? Neural and Behavioral
      Discrimination of Very Brief Acoustic Vowels.
AB  - The timbre of a sound plays an important role in our ability to discriminate
      between behaviorally relevant auditory categories, such as different vowels in
      speech. Here, we investigated, in the primary auditory cortex (A1) of
      anesthetized guinea pigs, the neural representation of vowels with impoverished
      timbre cues. Five different vowels were presented with durations ranging from 2
      to 128 ms. A psychophysical experiment involving human listeners showed that
      identification performance was near ceiling for the longer durations and degraded
      close to chance level for the shortest durations. This was likely due to spectral
      splatter, which reduced the contrast between the spectral profiles of the vowels
      at short durations. Effects of vowel duration on cortical responses were well
      predicted by the linear frequency responses of A1 neurons. Using mutual
      information, we found that auditory cortical neurons in the guinea pig could be
      used to reliably identify several vowels for all durations. Information carried
      by each cortical site was low on average, but the population code was accurate
      even for durations where human behavioral performance was poor. These results
      suggest that a place population code is available at the level of A1 to encode
      spectral profile cues for even very short sounds.

PMID- 25947233
TI  - Cysteamine treatment restores the in vitro ability to differentiate along the
      osteoblastic lineage of mesenchymal stromal cells isolated from bone marrow of a
      cystinotic patient.
AB  - BACKGROUND: Cystinosis is a rare autosomal recessive disease caused by mutations
      of the CTNS gene, which encodes for a lysosomal cystine/H(+) symporter. In mice,
      inactivation of the CTNS gene causes intralysosomal cystine accumulation and
      progressive organ damage that can be reversed, at least in part, by infusion of
      mesenchymal stromal cells (MSCs). Little is known on the mesenchymal compartment
      of cystinotic patients. The aim of the study was to test the phenotypical and
      functional properties of cystinotic MSCs (Cys-MSCs) isolated from bone marrow
      (BM) aspirate of a patient with nephropathic cystinosis. METHODS: Morphology,
      proliferative capacity (measured as population doublings), immunophenotype (by
      flow-cytometry) and immunomodulatory properties (as phytohemagglutinin-induced
      peripheral blood mononuclear cell proliferation) were analyzed. The osteogenic
      differentiation potential of Cys-MSCs was evaluated by histological staining
      (alkaline phosphatase activity, Alzarin Red and von Kossa staining)
      spectrophotometry and Quantitative Reverse Transcriptase Polymerase Chain
      Reaction for osteigenic markers in the presence and in the absence of cysteamine.
      Cys-MSCs were compared with those isolated and expanded ex vivo from three
      healthy donors (HD-MSCs). RESULTS: Despite a slightly lower proliferative
      capacity, Cys-MSCs displayed a characteristic spindle-shaped morphology and
      similar immunephenotype as HD-MSCs. Cys-MSCs and HD-MSCs prevented proliferation
      of PHA-stimulated allogeneic peripheral blood mononuclear cells to the same
      extent. After in vitro induction into osteoblasts, Cys-MSCs showed reduced
      alkaline phosphatase (ALP) activity, calcium depositions and expression of ALP
      and collagen type 1. When Cys-MSCs were treated in vitro with increasing doses of
      cysteamine (50-100-200 MUM/L) during the differentiation assay, recovery of Cys
      MSCs differentiation capacity into osteoblasts was observed. No difference in
      adipogenic differentiation was found between Cys-MSCs and HD-MSCs. CONCLUSIONS:
      Our results indicate that, as compared to HD-MSCs, Cys-MSCs show reduced ability
      to differentiate into osteoblasts, which can be reverted after cysteamine
      treatment.

PMID- 25947235
TI  - Povidone-iodine pleurodesis versus talc pleurodesis in preventing recurrence of
      malignant pleural effusion.
AB  - BACKGROUND: Malignant pleural effusions continue to be a common problem in
      patients with metastatic disease, leading to a significant reduction in quality
      of life with progressive dyspnea, dry cough, chest pain and reduced physical
      activity. This study was conducted to compare the efficacy, safety, and outcome
      of Talc Powder Pleurodesis (TPP) with Povidone-iodine Pleurodesis (PIP) through a
      chest drain as a palliative preventive treatment of recurrent malignant pleural
      effusion. METHODS: A total of 39 neoplastic patients with recurrent malignant
      pleural effusion were enrolled in a prospective randomized trial. Twenty-one
      patients received Talc pleurodesis (group A), and eighteen patients (group B)
      received Povidone-iodine pleurodesis. The continuous variables were expressed as
      mean values +/- standard deviation (SD) and compared using the unpaired t-test.
      The discrete variables were expressed as percentage and compared using the chi
      square test (chi(2)) test. p-values of less than 0.05 were considered
      significant. RESULTS: Our study included 11 males and 28 females, the mean age
      was (71.0 +/- 5.0) years for group A and (70.9 +/- 5.1) years for group B (non
      significant). Post-procedure analgesic requirements were recorded in both groups.
      Four patients in each group had fever (>38 degrees C) within 48 hours of the
      procedure. Both groups achieved good symptomatic relief. There were no in
      hospital deaths. The mean post-procedure hospital stay was (4.7 +/- 1.2) days for
      group A and (4.2 +/- 1.0) for group B (non-significant). At follow-up recurrence
      of significant pleural effusion requiring intervention was noted in four and five
      patients in group A and group B, respectively (non-significant difference).
      CONCLUSION: Povidone-iodine pleurodesis can be considered as a good alternative
      to Talc pleurodesis for recurrent malignant pleural effusion. The drug is
      available, cost effective, safe and can be administered through an intercostal
      drain and repeated if necessary.

PMID- 25947236
TI  - Mutagenicity of two herbicides widely used on soybean crops by the Allium cepa
      test.
AB  - This study evaluated the mutagenic effects of two herbicides: Clorimurom
      Nortox((r)) and Imazaquim Ultra Nortox((r)) widely used on soybean crops in
      Brazil. As a test system, Allium cepa assay was used, which analyzes the
      frequency of micronuclei (MN), chromosomal aberrations (CA) and the mitotic index
      (MI). Four concentrations of each herbicide (50, 75, 100 and 125 %) were tested
      in triplicate using distilled water (negative control) and methyl
      methanesulfonate (positive control) as controls. Three experimental repetitions
      were realized. Clorimurom Nortox((r)) showed a significantly lower MI than the
      negative control for the concentrations of 75, 100 and 125 %, but the CA was
      significantly increased at all concentrations. There was no recovery for CA or
      MI. The 125 % concentration of Imazaquim Ultra Nortox((r)) was cytotoxic and also
      exerted an effect on the other parameters. The concentration of 100 % showed a
      statistically increased MN and there was no recovery, while the 75 %
      concentration significantly affected CA, with recovery observed. The two
      herbicides showed mutagenic damage in Allium cepa cells, which implies a careful
      handling of these products, to minimize the risk of human and environmental
      contamination. 

PMID- 25947237
TI  - Characterization of smallholder pig breeding practices within a rural commune of
      North Central Vietnam.
AB  - This case study focused on a pig production system in a rural area of North
      Central Vietnam, with a focus on describing household pig breeding practices and
      estimating herd demographic parameters, particularly on reproduction. One hundred
      five households undertaking small-scale piglet production were surveyed, with
      information gathered on 3268 individual pigs. Pig keeping contributed variably to
      the overall household livelihood portfolio, with female household members as the
      main decision makers, contributors to labor, and beneficiaries of income from the
      pig enterprise. All households kept between one and four young or adult sows,
      with 69% of these sows of a local breed type (predominantly Mong Cai), 28% a
      cross between a local sow and an exotic sow (predominantly Large White), and the
      remainder (3%) as exotic sows. Eighty-eight percent of the piglets produced were
      cross-bred, while 12% were local breed. No adult males were kept by the surveyed
      households, reflecting the common use of artificial insemination for mating
      purposes. The most common breeding system practiced-the keeping of Mong Cai
      females and production of cross-bred piglets-capitalizes on the small body size
      and high fecundity of the sows and the fast growth rate and leanness of the cross
      bred piglets. The survey tool used, which was based on farmer recall of events
      over the preceding 12-month period, appeared to give reasonable results although
      some recall bias could be detected. This case study will serve as an entry point
      to planned broader scale characterization and development of pig breeding systems
      in North Central Vietnam.

PMID- 25947239
TI  - Lanthanide organic framework as a regenerable luminescent probe for Fe(3+).
AB  - A unique three-dimensional Tb-BTB framework (1) with two types of one-dimensional
      channels was obtained and structurally characterized, exhibiting high thermal
      stability. Luminescent investigations reveal that 1 can detect Fe(3+) with
      relatively high sensitivity and selectivity. Importantly, 1 as the luminescent
      probe of Fe(3+) can be simply and quickly regenerated, which represents a rare
      example in reported luminescent sensors of Fe(3+). 

PMID- 25947238
TI  - Epidemiological studies on Escherichia coli O157:H7 in Egyptian sheep.
AB  - In the present work, the epidemiological role of apparently healthy sheep in
      transmission of Escherichia coli O157:H7 in different seasons was investigated.
      Fecal samples (convenience sampling) of apparently healthy farmed sheep (three
      farms, n = 70) and from 15 wandering flocks fed on city wastes (n = 80) in the
      Giza governorate were examined. The samples were collected in spring under mild
      weather conditions and during hot summer to be compared. Out of the 150 animals,
      13 (8.7%) were E. coli O157 shedders. The 13 ovine sorbitol-negative E. coli O157
      were characterized by different PCR sets. The eae gene was detected in 11 isolate
      (85%), stx1 in 3 isolates (23%), stx2 in 8 isolates (62%), and finally the hlyA
      in 11 isolate (85%). Among the 13 isolates, 2 strains (15%) were positive for
      eae, stx1, stx2, and hlyA as gene combination, one isolate (8%) for eae, stx1,
      and hlyA, 5 isolates (38%) for eae, stx2, and hlyA, 1 isolate (8%) for eae and
      stx2, 2 isolates (15%) contained eae and hlyA, 1 isolate (8%) contained hlyA
      only, and finally, 1 isolate (8%) did not contain any of these genes. None of the
      isolates showed the gene combination eae stx1, stx1 hlyA, or stx2 hlyA. The
      results indicated significant association of unfavorable weather and management
      conditions on O157:H7 shedding while the age or sex did not play any role in this
      process.

PMID- 25947240
TI  - Interaction among CYP2C8, EPHX2, and CYP4A11 Gene Variants Significantly
      Increases the Risk for Ischemic Stroke in Chinese Populations.
AB  - AIM: Ischemic stroke (IS) is a multifactorial disease caused by environmental
      risk factors and genetic susceptibility. However, few studies have assessed
      whether gene-gene interactions among cytochrome P450 (CYP) pathway genes
      influence the risk of IS. The aim of the present study was to investigate the
      association of 10 variants of eight CYP pathway genes with IS and to determine
      whether these gene-gene interactions increase the risk of IS. METHODS: Ten
      variants of eight CYP pathway genes were examined using mass spectrometry methods
      in 396 patients with IS and 378 controls. Gene-gene interactions were analyzed
      using generalized multifactor dimensionality reduction (GMDR) methods. RESULTS:
      Apart fro m variant rs9333025, there were no significant differences in the
      genotype distributions of the other nine variants between the two groups using
      the single-locus analytical approach. However, the GMDR analysis showed a
      significant gene-gene interaction among rs17110453, rs751141, and rs9333025,
      which scored 10 for cross-validation consistency and nine for the sign test
      (p=0.011). Individual patients with the combination of 17110453CC, rs751141GG,
      and rs9333025GG had a significantly higher risk for IS than those with the
      combination of 17110453AA, rs751141AA, and rs9333025AA [odds ratio (OR)=2.86, 95%
      confidence interval (CI): 1.24-7.26, p=0.004]. Logistic regression analysis
      showed that certain gene-gene interactions among rs17110453, rs751141, and
      rs9333025 predict a higher risk for IS (OR=2.36, 95% CI: 1.228-5.297, p=0.005).
      CONCLUSION: The three-loci interaction may confer a higher risk for IS. The
      combinatorial analysis used in this study may be helpful to elucidate complex
      genetic risk factors for IS.

PMID- 25947241
TI  - Bioprospecting of microalgae for integrated biomass production and
      phytoremediation of unsterilized wastewater and anaerobic digestion centrate.
AB  - Eighteen microalgae, including two local isolates, were evaluated for their
      ability to grow and remove nutrients from unsterilized primary or secondary
      wastewater effluents as well as wastewater supplemented with nutrient-rich
      anaerobic digester centrate (ADC). Most of the tested species except several
      phylogenetically clustered Chlorella sorokiniana including local isolates and
      Scenedesmus strains were unable to grow efficiently. This may reflect the
      presence of certain genetic traits important for robust growth in the
      unsterilized wastewater. The maximum algal-specific growth rates and biomass
      density obtained in these bacterial-contaminated cultures were in the range of
      0.8-1 day(-1) and 250-350 mg L(-1), respectively. ADC supplementation was
      especially helpful to biologically treated secondary effluent with its lower
      initial macronutrient and micronutrient content. As a result of algal growth,
      total nitrogen and orthophosphate levels were reduced by as much as 90 and 70 %,
      respectively. Biological assimilation was estimated to be the main mechanism of
      nitrogen removal in primary and secondary effluents with ammonia volatilization
      and bacterial nitrification-denitrification contributing for cultures
      supplemented with ADC. Assimilation by algae served as the principal mechanism of
      orthophosphate remediation in secondary wastewater cultures, while chemical
      precipitation appeared also to be important for orthophosphate removal in primary
      wastewater. Overall, cultivation of microalgae in primary and primary + 5 % ADC
      may be more favorable from an economical and sustainability perspective due to
      elimination of the costly and energy-intensive biological treatment step. These
      findings demonstrate that unsterilized wastewater and ADC can serve as critical
      nutrient sources for biomass generation and that robust microalgae can be potent
      players in wastewater phytoremediation.

PMID- 25947242
TI  - Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) production by Haloarchaeon
      Halogranum amylolyticum.
AB  - Haloarchaea is an important group of polyhydroxyalkanoate (PHA)-accumulating
      organisms. However, few promising haloarchaeal species for economical and
      efficient PHA production have been reported. Here, we first discovered that
      Halogranum amylolyticum TNN58 could efficiently accumulate poly(3-hydroxybutyrate
      co-3-hydroxyvalerate) (PHBV) with a high 3-hydroxyvalerate (3HV) fraction using
      glucose as carbon source. Briefly, transmission electron microscopy (TEM)
      analysis revealed the presence of a large number of PHA granules in the cells.
      Gas chromatography-mass spectrometry (GC-MS) and proton nuclear magnetic
      resonance ((1)H NMR) analyses showed that PHAs synthesized from glucose was PHBV.
      Moreover, the 3HV content reached 20.1 mol%, which is the highest 3HV fraction
      thus far reported, as for PHBV produced by the wild-type strains grown on
      unrelated carbon courses. Fermentation experiments suggested that nitrogen
      limited MG medium was better than nutrient-rich NOMG and AS168 medium for PHBV
      production. Additionally, glucose was the most suitable carbon source among the
      tested carbon sources. Interestingly, PHBV accumulation was almost paralleled by
      cell growth and glucose consumption. By applying the fed-batch process in
      fermentor, the PHBV production and cell dry weight were increased by
      approximately eight and four times, respectively, as compared with those of the
      batch process in shaking flasks. The classical PHA synthase genes were
      successfully cloned via consensus-degenerate hybrid oligonucleotide primers
      (CODEHOPs) and high-efficiency thermal asymmetric interlaced (hiTAIL) PCR
      methods. This finding suggested that H. amylolyticum shows promising potential in
      the low-cost biotechnological production of PHBV after further process
      optimization. 

PMID- 25947243
TI  - A first continuous 4-aminoantipyrine (4-AAP)-based screening system for directed
      esterase evolution.
AB  - Esterases hydrolyze ester bonds with an often high stereoselectivity as well as
      regioselectivity and are therefore industrially employed in the synthesis of
      pharmaceuticals, in food processing, and in laundry detergents. Continuous
      screening systems based on p-nitrophenyl- (e.g., p-nitrophenyl acetate) or
      umbelliferyl-esters are commonly used in directed esterase evolution campaigns.
      Ongoing challenges in directed esterase evolution are screening formats which
      offer a broad substrate spectrum, especially for complex aromatic substrates. In
      this report, a novel continuous high throughput screening system for indirect
      monitoring of esterolytic activity was developed and validated by detection of
      phenols employing phenyl benzoate as substrate and p-nitrobenzyl esterase (pNBEBL
      from Bacillus licheniformis) as catalyst. The released phenol directly reacts
      with 4-aminoantipyrine yielding the red compound 1,5-dimethyl-4-(4-oxo-cyclohexa
      2,5-dienylidenamino)-2-phenyl-1,2-dihydro-pyrazol-3-one. In this continuous B.
      licheniformis esterase activity detection system (cBLE-4AAP), the product
      formation is followed through an increase in absorbance at 509 nm. The cBLE-4AAP
      screening system was optimized in 96-well microtiter plate format in respect to
      standard deviation (5 %), linear detection range (15 to 250 MUM), lower detection
      limit (15 MUM), and pH (7.4 to 10.4). The cBLE-4AAP screening system was
      validated by screening a random epPCR pNBEBL mutagenesis library (2000 clones)
      for improved esterase activity at elevated temperatures. Finally, the variant T3
      (Ser378Pro) was identified which nearly retains its specific activity at room
      temperature (WT 1036 U/mg and T3 929 U/mg) and shows compared to WT a 4.7-fold
      improved residual activity after thermal treatment (30 min incubation at 69.4 
      degrees C; WT 170 U/mg to T3 804 U/mg).

PMID- 25947244
TI  - Elucidating the effects of arginine and lysine on a monoclonal antibody C
      terminal lysine variation in CHO cell cultures.
AB  - C-terminal lysine variants are commonly observed in monoclonal antibodies (mAbs)
      and found sensitive to process conditions, especially specific components in
      culture medium. The potential roles of media arginine (Arg) and lysine (Lys) in
      mAb heavy chain C-terminal lysine processing were investigated by monitoring the
      lysine variant levels under various Arg and Lys concentrations. Both Arg and Lys
      were found to significantly affect lysine variant level. Specifically, lysine
      variant level increased from 18.7 to 31.8 % when Arg and Lys concentrations were
      increased from 2 to 10 mM. Since heterogeneity of C-terminal lysine residues is
      due to the varying degree of proteolysis by basic carboxypeptidases (Cps), enzyme
      (basic Cps) level, pH conditions, and product (Arg and Lys) inhibition, which
      potentially affect the enzymatic reaction, were investigated under various Arg
      and Lys conditions. Enzyme level and pH conditions were found not to account for
      the different lysine variant levels, which was evident from the minimal variation
      in transcription level and intracellular pH. On the other hand, product
      inhibition effect of Arg and Lys on basic Cps was evident from the notable
      intracellular and extracellular Arg and Lys concentrations comparable with Ki
      values (inhibition constant) of basic Cps and further confirmed by cell-free
      assays. Additionally, a kinetic study of lysine variant level during the cell
      culture process enabled further characterization of the C-terminal lysine
      processing.

PMID- 25947245
TI  - Glucose concentration alters dissolved oxygen levels in liquid cultures of
      Beauveria bassiana and affects formation and bioefficacy of blastospores.
AB  - The filamentous fungus Beauveria bassiana is an economically important pathogen
      of numerous arthropod pests and is able to grow in submerged culture as filaments
      (mycelia) or as budding yeast-like blastospores. In this study, we evaluated the
      effect of dissolved oxygen and high glucose concentrations on blastospore
      production by submerged cultures of two isolates of B. bassiana, ESALQ1432 and
      GHA. Results showed that maintaining adequate dissolved oxygen levels coupled
      with high glucose concentrations enhanced blastospore yields by both isolates.
      High glucose concentrations increased the osmotic pressure of the media and
      coincided with higher dissolved oxygen levels and increased production of
      significantly smaller blastospores compared with blastospores produced in media
      with lower concentrations of glucose. The desiccation tolerance of blastospores
      dried to less than 2.6 % moisture was not affected by the glucose concentration
      of the medium but was isolate dependent. Blastospores of isolate ESALQ1432
      produced in media containing 140 g glucose L(-1) showed greater virulence toward
      whitefly nymphs (Bemisia tabaci) as compared with blastospores produced in media
      containing 40 g glucose L(-1). These results suggest a synergistic effect between
      glucose concentration and oxygen availability on changing morphology and
      enhancing the yield and efficacy of blastospores of B. bassiana, thereby
      facilitating the development of a cost-effective production method for this
      blastospore-based bioinsecticide.

PMID- 25947246
TI  - The effect of storage conditions on microbial community composition and
      biomethane potential in a biogas starter culture.
AB  - A new biogas process is initiated by adding a microbial community, typically in
      the form of a sample collected from a functional biogas plant. This inoculum has
      considerable impact on the initial performance of a biogas reactor, affecting
      parameters such as stability, biogas production yields and the overall efficiency
      of the anaerobic digestion process. In this study, we have analyzed changes in
      the microbial composition and performance of an inoculum during storage using
      barcoded pyrosequencing of bacterial and archaeal 16S ribosomal RNA (rRNA) genes,
      and determination of the biomethane potential, respectively. The inoculum was
      stored at room temperature, 4 and -20  degrees C for up to 11 months and
      cellulose was used as a standard substrate to test the biomethane potential.
      Storage up to 1 month resulted in similar final methane yields, but the rate of
      methane production was reduced by storage at -20  degrees C. Longer storage times
      resulted in reduced methane yields and slower production kinetics for all storage
      conditions, with room temperature and frozen samples consistently giving the best
      and worst performance, respectively. Both storage time and temperature affected
      the microbial community composition and methanogenic activity. In particular,
      fluctuations in the relative abundance of Bacteroidetes were observed.
      Interestingly, a shift from hydrogenotrophic methanogens to methanogens with the
      capacity to perform acetoclastic methanogensis was observed upon prolonged
      storage. In conclusion, this study suggests that biogas inocula may be stored up
      to 1 month with low loss of methanogenic activity, and identifies bacterial and
      archaeal species that are affected by the storage. 

PMID- 25947247
TI  - Yarrowia lipolytica: recent achievements in heterologous protein expression and
      pathway engineering.
AB  - The oleaginous yeast Yarrowia lipolytica has become a recognized system for
      expression/secretion of heterologous proteins. This non-conventional yeast is
      currently being developed as a workhorse for biotechnology by several research
      groups throughout the world, especially for single-cell oil production, whole
      cell bioconversion and upgrading of industrial wastes. This mini-review presents
      established tools for protein expression in Y. lipolytica and highlights novel
      developments in the areas of promoter design, surface display, and host strain or
      metabolic pathway engineering. An overview of the industrial and commercial
      biotechnological applications of Y. lipolytica is also presented. 

PMID- 25947249
TI  - Using electric field to enhance the activity of anammox bacteria.
AB  - Electric field was applied to enhance the activity of anaerobic ammonium
      oxidation (anammox) bacteria for nitrogen removal in this study. The effect of
      different distributive modes with the total electric field time of 6 h/24 h (R2)
      and 18 h/24 h (R3) at 2 V/cm was determined through long-term tests. With the
      continuous application time increasing from 3 to 9 h in R3 (1 to 3 h in R2), the
      total nitrogen removal rate (NRR) showed an acceleration trend. When the electric
      field was applied continuously for 9 h (R3, mode 3, application-rest time: 9 h-3
      h), the NRR dramatically increased 38.7 % over that of control on day 160.
      Besides, it was demonstrated that the increase of crude enzyme activities and the
      cell quantities were the main reasons for the enhancement of nitrogen removal
      performance of the anammox process. Additionally, transmission electron
      microscope observation proved the morphological change of anammox biomass under
      electric field application.

PMID- 25947250
TI  - Changes in intestinal bacterial communities are closely associated with shrimp
      disease severity.
AB  - Increasing evidence has revealed a close association between intestinal bacterial
      communities and human health. However, given that host phylogeny shapes the
      composition of intestinal microbiota, it is unclear whether changes in intestinal
      microbiota structure in relation to shrimp health status. In this study, we
      collected shrimp and seawater samples from ponds with healthy and diseased
      shrimps to understand variations in bacterial communities among habitats (water
      and intestine) and/or health status. The bacterial communities were clustered
      according to the original habitat and health status. Habitat and health status
      constrained 14.6 and 7.7 % of the variation in bacterial communities,
      respectively. Changes in shrimp intestinal bacterial communities occurred in
      parallel with changes in disease severity, reflecting the transition from a
      healthy to a diseased state. This pattern was further evidenced by 38 bacterial
      families that were significantly different in abundance between healthy and
      diseased shrimps; moderate changes were observed in shrimps with sub-optimal
      health. In addition, within a given bacterial family, the patterns of enrichment
      or decrease were consistent with the known functions of those bacteria.
      Furthermore, the identified 119 indicator taxa exhibited a discriminative pattern
      similar to the variation in the community as a whole. Overall, this study
      suggests that changes in intestinal bacterial communities are closely associated
      with the severity of shrimp disease and that indicator taxa can be used to
      evaluate shrimp health status.

PMID- 25947252
TI  - Effect of oral IQoro R and palatal plate training in post-stroke, four-quadrant
      facial dysfunction and dysphagia: A comparison study.
AB  - CONCLUSION: Training with either a palatal plate (PP) or an oral IQoro(R) screen
      (IQS) in patients with longstanding facial dysfunction and dysphagia after stroke
      can significantly improve facial activity (FA) in all four facial quadrants as
      well as swallowing capacity (SC). Improvements remained at late follow-up. The
      training modalities did not significantly differ in ameliorating facial
      dysfunction and dysphagia in these patients. However, IQS training has practical
      and economic advantages over PP training. OBJECTIVES: This study compared PP and
      oral IQS training in terms of (i) effect on four-quadrant facial dysfunction and
      dysphagia after a first-ever stroke, and (ii) whether the training effect
      persisted at late follow-up. METHODS: Patients were included during two periods;
      13 patients in 2005-2008 trained with a PP, while 18 patients in 2009-2012
      trained with an IQS. Four-quadrant facial dysfunction was assessed with an FA
      test and swallowing dysfunction with a SC test: before and after a 3-month
      training period and at late follow-up. FA and SC significantly improved (p <
      0.001) in both groups. FA test scores after training and at late follow-up did
      not differ significantly between the groups, irrespective of whether the interval
      between stroke incidence and the start of training was long or short.

PMID- 25947251
TI  - Lactic acid fermentation as a tool to enhance the antioxidant properties of
      Myrtus communis berries.
AB  - BACKGROUND: Myrtle (Myrtus communis L.) is a medicinal and aromatic plant
      belonging to Myrtaceae family, which is largely diffused in the Mediterranean
      areas and mainly cultivated in Tunisia and Italy. To the best of our knowledge,
      no studies have already considered the use of the lactic acid fermentation to
      enhance the functional features of M. communis. This study aimed at using a
      selected lactic acid bacterium for increasing the antioxidant features of myrtle
      berries, with the perspective of producing a functional ingredient, dietary
      supplement or pharmaceutical preparation. The antioxidant activity was
      preliminarily evaluated through in vitro assays, further confirmed through ex
      vivo analysis on murine fibroblasts, and the profile of phenol compounds was
      characterized. RESULTS: Myrtle berries homogenate, containing yeast extract
      (0.4%, wt/vol), was fermented with Lactobacillus plantarum C2, previously
      selected from plant matrix. Chemically acidified homogenate, without bacterial
      inoculum and incubated under the same conditions, was used as the control.
      Compared to the control, fermented myrtle homogenate exhibited a marked
      antioxidant activity in vitro. The radical scavenging activity towards DPPH
      increased by 30%, and the inhibition of linoleic acid peroxidation was twice. The
      increased antioxidant activity was confirmed using Balb 3 T3 mouse fibroblasts,
      after inducing oxidative stress, and determining cell viability and radical
      scavenging activity through MTT and DCFH-DA assays, respectively. The lactic acid
      fermentation allowed increased concentrations of total phenols, flavonoids and
      anthocyanins, which were 5-10 times higher than those found for the non-fermented
      and chemically acidified control. As shown by HPLC analysis, the main increases
      were found for gallic and ellagic acids, and flavonols (myricetin and quercetin).
      The release of these antioxidant compounds would be strictly related to the
      esterase activities of L. plantarum. CONCLUSIONS: The lactic acid fermentation of
      myrtle berries is a suitable tool for novel applications as functional food
      dietary supplements or pharmaceutical preparations.

PMID- 25947253
TI  - Asymmetric synthesis of quaternary alpha-fluoro-beta-keto-amines via
      detrifluoroacetylative Mannich reactions.
AB  - Efficient asymmetric detrifluoroacetylative Mannich addition reactions between 2
      fluoro-1,3-di-ketones/hydrates and chiral N-sulfinyl-imines via C-C bond cleavage
      were reported, which afforded C-F quaternary alpha-fluoro-beta-keto-amines with
      excellent yields and high diastereoselectivity. 

PMID- 25947248
TI  - Distribution of ammonia-oxidizing archaea and bacteria in plateau soils across
      different land use types.
AB  - Ammonia oxidation is known to be performed by both ammonia-oxidizing archaea
      (AOA) and bacteria (AOB), although their relative significance to nitrification
      process in soil ecosystems remains controversial. The distribution of AOA and AOB
      in plateau soils with different land use types and the influential factors
      remains unclear. The present study investigated the abundance and structure of
      AOA and AOB communities in upland soils adjacent to Erhai Lake in the Yunnan
      Plateau (China). Quantitative PCR assays indicated a large variation in the
      community size of AOA and AOB communities, with the numerical dominance of AOA
      over AOB in most of soils. Clone library analysis illustrated a marked shift in
      the structure of soil AOA and AOB communities. A high abundance of Nitrososphaera
      and Nitrosotalea-like AOA was observed, while Nitrosospira-like species
      predominated in AOB. AOA and AOB abundance was positively influenced by total
      nitrogen and moisture content, respectively. Moreover, moisture content might be
      a key determinant of AOA community composition, while C/N and nitrate nitrogen
      played an important role in shaping AOB community composition. However, further
      efforts will be necessary in order to elucidate the links between soil AOA and
      AOB and land use.

PMID- 25947254
TI  - Characterization of the thermolysis products of Nafion membrane: A potential
      source of perfluorinated compounds in the environment.
AB  - The thermal decomposition of Nafion N117 membrane, a typical perfluorosulfonic
      acid membrane that is widely used in various chemical technologies, was
      investigated in this study. Structural identification of thermolysis products in
      water and methanol was performed using liquid chromatography-electrospray
      ionization-tandem mass spectrometry (LC/ESI-MS/MS). The fluoride release was
      studied using an ion-chromatography system, and the membrane thermal stability
      was characterized by thermogravimetric analysis. Notably, several types of
      perfluorinated compounds (PFCs) including perfluorocarboxylic acids were detected
      and identified. Based on these data, a thermolysis mechanism was proposed
      involving cleavage of both the polymer backbone and its side chains by attack of
      radical species. This is the first systematic report on the thermolysis products
      of Nafion by simulating its high-temperature operation and disposal process via
      incineration. The results of this study indicate that Nafion is a potential
      environmental source of PFCs, which have attracted growing interest and concern
      in recent years. Additionally, this study provides an analytical justification of
      the LC/ESI-MS/MS method for characterizing the degradation products of polymer
      electrolyte membranes. These identifications can substantially facilitate an
      understanding of their decomposition mechanisms and offer insight into the proper
      utilization and effective management on these membranes. 

PMID- 25947255
TI  - Expectations for methodology and translation of animal research: a survey of
      health care workers.
AB  - BACKGROUND: Health care workers (HCW) often perform, promote, and advocate use of
      public funds for animal research (AR); therefore, an awareness of the empirical
      costs and benefits of animal research is an important issue for HCW. We aim to
      determine what health-care-workers consider should be acceptable standards of AR
      methodology and translation rate to humans. METHODS: After development and
      validation, an e-mail survey was sent to all pediatricians and pediatric
      intensive care unit nurses and respiratory-therapists (RTs) affiliated with a
      Canadian University. We presented questions about demographics, methodology of
      AR, and expectations from AR. Responses of pediatricians and nurses/RTs were
      compared using Chi-square, with P < .05 considered significant. RESULTS: Response
      rate was 44/114(39%) (pediatricians), and 69/120 (58%) (nurses/RTs). Asked about
      methodological quality, most respondents expect that: AR is done to high quality;
      costs and difficulty are not acceptable justifications for low quality; findings
      should be reproducible between laboratories and strains of the same species; and
      guidelines for AR funded with public money should be consistent with these
      expectations. Asked about benefits of AR, most thought that there are
      sometimes/often large benefits to humans from AR, and disagreed that "AR rarely
      produces benefit to humans." Asked about expectations of translation to humans
      (of toxicity, carcinogenicity, teratogenicity, and treatment findings), most:
      expect translation >40% of the time; thought that misleading AR results should
      occur <21% of the time; and that if translation was to occur <20% of the time,
      they would be less supportive of AR. There were few differences between
      pediatricians and nurses/RTs. CONCLUSIONS: HCW have high expectations for the
      methodological quality of, and the translation rate to humans of findings from
      AR. These expectations are higher than the empirical data show having been
      achieved. Unless these areas of AR significantly improve, HCW support of AR may
      be tenuous.

PMID- 25947256
TI  - A systematic review on the use of exercise interventions for individuals with
      myeloid leukemia.
AB  - PURPOSE: The aim of this study is to explore the current literature examining the
      feasibility, safety, and efficacy of exercise interventions for individuals with
      myeloid leukemia. METHODS: A literature search was conducted in Ovid MEDLINE,
      AMED, Embase, PsycINFO, CINAHL, CENTRAL, and Web of Science using the terms
      "exercise" OR "physical activity" AND "myeloid leukemia." Two reviewers performed
      duplicate title/abstract and full text screening of clinical trials comparing
      outcomes for people with myeloid leukemia participating in an exercise program.
      Initial searches yielded 149 articles. Two reviewers independently extracted data
      using piloted forms and assessed risk of bias using Cochrane's tool. Data was
      extracted in relation to the study population, study intervention, comparator
      intervention, and outcomes assessed. RESULTS: Five trials were included in this
      review after 20 full-text articles were screened. Risk of bias was determined to
      be high in all five studies. Adherence rates were found to be low (<30 %) in all
      studies measuring this outcome. Positive improvements were found for fatigue,
      physical functioning, quality of life, and psychological distress for patients
      with AML; however, not all findings were significant. Leukocyte and BCR-ABL1
      levels increased significantly post-exercise for participants with CML. Only one
      adverse event was reported. CONCLUSIONS: Exercise interventions appear safe and
      feasible for individuals with AML. Not enough evidence was presented to comment
      on the feasibility of exercise programs for individuals with CML. Inconclusive
      evidence was found on the effectiveness of exercise to minimize side effects for
      participants with AML.

PMID- 25947257
TI  - Palonosetron in combination with 1-day versus 3-day dexamethasone to prevent
      nausea and vomiting in patients receiving paclitaxel and carboplatin.
AB  - PURPOSE: The aim of the present study was to evaluate the efficacy and toxicity
      of palonosetron (PAL) and dexamethasone (DEX) on day 1 only in patients with
      gynecologic cancer receiving paclitaxel combined with carboplatin (TC). The
      primary endpoint was to evaluate the complete response (CR) rate in the delayed
      phase. METHODS: This study was a randomized phase 2. Regardless of assignment to
      either study arm, all patients received an intravenous prophylactic regimen of
      DEX (20 mg) within 15 min and then an intravenous dose of PAL (0.75 mg) as a
      bolus given 30 min before initiation of TC on day 1. Patients in the DEX 1-day
      group received no additional DEX on days 2 and 3. Patients in the DEX 3-day group
      received DEX (8 mg) orally on days 2 and 3. RESULTS: Eighty-two patients had
      evaluable data on the primary outcome. The CR rates in the delayed phase between
      the two groups were not statistically significantly different (3-day group, 76.9
      % [30/39]; 1-day group 69.8 % [30/43]; p = 0.4652). The frequency of constipation
      and insomnia which were antiemetic treatment-related adverse events was similar
      between two groups, and no serious adverse events occurred. CONCLUSIONS:
      Administration of a combination of PAL and DEX 1 day may prevent chemotherapy
      induced nausea and vomiting (CINV) in the delayed phase for TC as well as
      administration of DEX 3 days. Further evaluation of the antiemetic regimen of
      combination of PAL and DEX 1 day for TC is warranted in future phase 3 trials.

PMID- 25947258
TI  - Genome-wide transcriptional profiling analysis reveals annexin A6 as a novel EZH2
      target gene involving gastric cellular proliferation.
AB  - A histone methyltransferase enhancer of zeste homologue 2 (EZH2) catalyzes
      trimethylation at histone H3 lysine27 (H3K27me3) and is frequently dysregulated
      in a wide range of human cancers. EZH2-mediated gene silencing contributes to
      carcinogenesis and regulates stem cell maintenance and differentiation; however,
      the underlining mechanisms remain to be completely understood. Here, we found
      that downregulation of EZH2 by RNA interference (RNAi) in gastric cancer cells
      suppresses cell growth, migration, invasion, and induces cell cycle arrest.
      Transcriptome analysis identified 1223 EZH2 responsive genes upon EZH2 knockdown.
      These genes are involved in the biological processes of cell cycle, proliferation
      and metastasis. Particularly, we found that annexin A6 (ANXA6) is a new target of
      EZH2 and is repressed in gastric cancer cells. Restoration of ANXA6 expression
      inhibits gastric cellular proliferation. We further demonstrated that EZH2
      mediated H3K27me3, rather than promoter DNA methylation, is primarily responsible
      for ANXA6 inhibition. Taken together, our results provide a framework for
      understanding EZH2 biology and reveal ANXA6 as a new EZH2 target involving
      gastric cellular proliferation. 

PMID- 25947260
TI  - ATLANTIC: another reason to investigate the disconnect between stent thrombosis
      and mortality?

PMID- 25947259
TI  - Molecular Mechanisms of Vascular Calcification in Chronic Kidney Disease: The
      Link between Bone and the Vasculature.
AB  - Vascular calcification is highly prevalent in patients with chronic kidney
      disease (CKD) and increases mortality in those patients. Impaired calcium and
      phosphate homeostasis, increased oxidative stress, and loss of calcification
      inhibitors have been linked to vascular calcification in CKD. Additionally,
      impaired bone may perturb serum calcium/phosphate and their key regulator,
      parathyroid hormone, thus contributing to increased vascular calcification in
      CKD. Therapeutic approaches for CKD, such as phosphate binders and
      bisphosphonates, have been shown to ameliorate bone loss as well as vascular
      calcification. The precise mechanisms responsible for vascular calcification in
      CKD and the contribution of bone metabolism to vascular calcification have not
      been elucidated. This review discusses the role of systemic uremic factors and
      impaired bone metabolism in the pathogenesis of vascular calcification in CKD.
      The regulation of the key osteogenic transcription factor Runt-related
      transcription factor 2 (Runx2) and the emerging role of Runx2-dependent receptor
      activator of nuclear factor kappa-B ligand (RANKL) in vascular calcification of
      CKD are emphasized. 

PMID- 25947261
TI  - Urinary Iodine Excretion among Nepalese School Children in Terai Region.
AB  - OBJECTIVES: To assess the current iodine status among school children in Terai
      region of Nepal. METHODS: A cross sectional study was conducted in 2012 among the
      school children aged 6-12y in three Terai districts (Siraha, Saptari and Jhapa)
      of eastern Nepal. A total of 1105 casual urine samples were collected from
      children of different schools of above districts. Urinary iodine excretion was
      estimated using ammonium persulphate digestion method. RESULTS: The median
      urinary iodine excretion in school children was 226.33MUg/L (234.16MUg/L,
      229.25MUg/L and 210.67MUg/L in Siraha, Saptari and Jhapa districts respectively).
      About 12.7% (n = 140) children were found to be iodine deficient and 34.2% (n =
      378) children had excessive iodine nutrition. CONCLUSIONS: There was good
      improvement in iodine nutrition among children in Terai region, with a large part
      of population showing excessive iodine nutrition.

PMID- 25947262
TI  - Assessment of Musculoskeletal Function and its Correlation with Radiological
      Joint Score in Children with Hemophilia A.
AB  - OBJECTIVE: To evaluate the functional independence of children with hemophilia A
      and its correlation to radiological joint score. METHODS: The present cross
      sectional study was conducted at SPMCHI, SMS Medical College, Jaipur, India.
      Children in the age group of 4-18 y affected with severe, moderate and mild
      hemophilia A and with a history of hemarthrosis who attended the OPD, emergency
      or got admitted in wards of SPMCHI, SMS Medical College were examined.
      Musculoskeletal function was measured in 98 patients using Functional
      Independence Score in Hemophilia (FISH) and index joints (joints most commonly
      affected with repeated bleeding) were assessed radiologically with plain X rays
      using Pettersson score. RESULTS: The mean FISH score was 28.07 +/- 3.90 (range 17
      32) with squatting, running and step climbing as most affected tasks. The mean
      Pettersson score was 3.8 +/- 3.2. A significant correlation was found between
      mean Pettersson score and FISH (r = -0.875, P < 0.001) with knee and elbow having
      r = -0.810 and -0.861 respectively, but not in case of ankle with r = -0.420 (P
      0.174). CONCLUSIONS: The FISH and radiological joint (Pettersson's) scores may be
      extremely useful in the clinical practice in the absence of magnetic resonance
      imaging (MRI), which is considered very sensitive to detect early joint damage,
      but at a cost that makes it relatively inaccessible. FISH seems to be a reliable
      tool for assessment of functional independence in patients with hemophilia A.

PMID- 25947263
TI  - Kerion.

PMID- 25947264
TI  - Efficacy of Single Dose Oral Paracetamol in Reducing Pain During Examination for
      Retinopathy of Prematurity: A Blinded Randomized Controlled Trial.
AB  - OBJECTIVE: To investigate the efficacy of paracetamol in reducing pain during
      examination for retinopathy of prematurity (ROP) in preterm infants. METHODS: A
      total of 114 infants undergoing eye examination for retinopathy of prematurity
      screening were prospectively randomized. Topical anesthetic (Proparacaine;
      Alcaine(r) drop 0.5%) was applied 30 s before the eye examination in all the
      infants. The infants in the intervention group (Group 1, n = 58) received 15
      mg/kg of oral paracetamol, 60 min before the examination. The control group
      (Group 2, n = 56) received the same volume of sterile water per oral with an
      opaque syringe. Primary outcome measurement was pain assessed by Premature Infant
      Pain Profile (PIPP) score. Secondary outcome measurements were tachycardia (>180
      bpm)/bradycardia (<100 bpm), desaturations (<85% for >10 s), and crying time.
      RESULTS: The groups were similar for gestational age, birthweight or postnatal
      age at examination. The intervention group had a significantly lower mean PIPP
      score during eye examination, following insertion of the speculum [Group 1:12 (9
      13) vs. Group 2:14 (13-15), p 0.001]. There were no significant differences
      between the groups with regard to crying time and the number of the patients with
      tachycardia/bradycardia and desaturation. CONCLUSIONS: Oral paracetamol modestly
      reduces pain scores during eye examinations. Further cross-over trials on dose
      and frequency of paracetamol and combination of pharmacological with non
      pharmacological approaches and paracetamol alone as a single agent in significant
      pain reduction are needed.

PMID- 25947265
TI  - Multiple Segmental Hemangiomas Over One Half of the Body - A Rare Feature of
      PHACES Syndrome.

PMID- 25947267
TI  - Novel Mutation in an Indian Patient with Transcobalamin II Deficiency.

PMID- 25947266
TI  - Adolescents and Body Image: A Cross Sectional Study.
AB  - OBJECTIVES: To assess proportion of adolescents perceiving their body image as
      normal and to study association between body shape, self-esteem and body mass
      index; each with body image perception. METHODS: A cross sectional study was
      conducted among pre university college (PUC) students of Udupi taluk. A total of
      550 students in the age group of 15-19y were randomly selected from 11 PUC's:
      four were taken from government and unaided strata respectively and three from
      aided. The PUC's were selected based on proportional allocation from a total of
      48 PUC's. From each PUC a class was randomly chosen as a cluster; all students in
      the class were included. Body shape questionnaire and Rosenberg self-esteem scale
      were used to assess body shape concerns and self-esteem respectively. Height and
      weight was measured and body mass index was calculated. SPSS version 15 has been
      used for analysis. Results were tabulated using frequency distribution and
      proportions. Multinomial logistic regression was done. RESULTS: About 38 % of the
      respondents perceived their body image as normal. Body shape [OR = 0.48,95 % CI:
      0.305, 0.76], self-esteem [OR = 6.12,95 % CI: 2.76, 13.9] and body mass index [OR
      = 4.65,95 % CI: 2.13,10.12] were found to be independently associated with body
      image perception. CONCLUSIONS: Educational institutes are a major component of
      adolescent's lives; the identified factors for body image perception should be
      taken into consideration and appropriate educational efforts to be incorporated
      into the routine curriculum.

PMID- 25947268
TI  - Ventilator-Associated Pneumonia in Pediatric Intensive Care Unit: Correspondence.

PMID- 25947269
TI  - Ventilator-Associated Pneumonia in Pediatric Intensive Care Unit: Authors' Reply.

PMID- 25947270
TI  - Relationship between Obesity Indices and Pulmonary Function Parameters in Obese
      Thai Children and Adolescents.
AB  - OBJECTIVE: To determine the correlation between various obesity indices and
      pulmonary function parameters in obese Thai children and adolescents. METHODS:
      Obese children and adolescents aged from 8 to 18 y and diagnosed under the
      criteria of International Obesity Task Force (IOTF) were enrolled. Anthropometric
      and body composition measurements (bioelectrical impedance analysis) of all
      eligible participants were recorded. Pulmonary function studies (spirometry and
      body plethysmography) were also performed on the same day. RESULTS: Forty-five
      children and adolescents [84 % boys; mean age 11.9 +/- 2.4 y; mean BMI 31.8 +/-
      5.1 kg/m(2); and, mean body mass index (BMI) z-score 3.2 +/- 0.5] were studied.
      Mean body fat percentage, mean fat mass index (FMI), mean fat free mass index,
      and mean truncal fat percentage were 47.4 +/- 10.2 %, 15.2 +/- 5.2 kg/m(2), 16.3
      +/- 3.1 kg/m(2), and 47.7 +/- 11.5 %, respectively. Abnormal lung functions were
      found in 73.2 % of subjects; the most common was decreased functional residual
      capacity (FRC) (29 cases; 64.4 %). There was a negative correlation between FRC
      and BMI z-score (r = -0.32; p 0.03), waist-height ratio (r = -0.32; p 0.02), body
      fat percentage (r = -0.32; p 0.03), FMI (r = -0.36; p 0.02), and truncal fat
      percentage (r = -0.32; p 0.04). Obese individuals who had FMI > 17 kg/m(2) were
      5.7 times more likely to have decreased FRC than those who had lower FMI (95 % CI
      1.1-29.7; p 0.016). CONCLUSIONS: Decreased FRC was the most common pulmonary
      function abnormality in obese children and adolescents. BMI z-score, waist-height
      ratio, body fat percentage, FMI, and truncal fat percentage were all negatively
      correlated with FRC. FMI had the highest negative correlation. Obese individuals
      with FMI > 17 kg/m(2) had a 5.7 times increased risk of low FRC. Appropriate
      planning for respiratory care and follow-up may be required in this population.

PMID- 25947271
TI  - Electrochemical doping of three-dimensional graphene networks used as efficient
      electrocatalysts for oxygen reduction reaction.
AB  - Three-dimensional graphene networks (3DGNs) doped with a mono-heteroatom of N or
      B, or dual-heteroatoms of N and B were fabricated, which exhibit excellent oxygen
      reduction reaction (ORR) performance. Importantly, the onset potential and
      current density of N and B co-doped 3DGNs are comparable to those of the
      commercial Pt (30%)/C catalyst. 

PMID- 25947272
TI  - Significant excess of early deaths after prehospital ticagrelor: The ATLANTIC
      trial challenge.
AB  - The recently published Administration of Ticagrelor in the Cath Lab or in the
      Ambulance for New ST Elevation Myocardial Infarction to Open the Coronary Artery
      (ATLANTIC) trial concluded that prehospital administration of ticagrelor in
      patients with acute STEMI appeared to be safe but did not improve pre-PCI
      coronary reperfusion. The ATLANTIC data fully support the PLATO Angiographic
      Substudy denying early benefit of ticagrelor, and correspond well with lack of
      immediate clinical benefit including the early PCI "death paradox" in PLATO-USA
      patients. Finally, there were significantly (p=0.043) more deaths in early
      ticagrelor ATLANTIC arm (odds ratio 3.18 (1.02-9.90) challenging stent thrombosis
      reduction. Indeed, ATLANTIC represents an important step for our better
      understanding of ticagrelor, although the confirmation of the PLATO mortality
      wonder in an adequately powered PEGASUS (TIMI-54) to be reported in 2015 will be
      vital for ticagrelor future. 

PMID- 25947273
TI  - Why Optogenetics Needs in Vivo Neurochemistry.
AB  - In neuroscience, the consequences of optogenetic manipulation are often studied
      using in vivo electrophysiology and by observing behavioral changes induced by
      light stimulation in genetically targeted rodents. In contrast, reports on the in
      vivo neurochemical effects of optogenetic stimulation are scarce despite the
      improving quality of analytical techniques available to monitor biochemical
      compounds involved in neurotransmission. This intriguing lack of neurochemical
      information suggests the existence of unknown or misunderstood factors hampering
      the expected rise of a novel specialty putatively be termed "neurochemical
      optogenetics". 

PMID- 25947274
TI  - Etiology of renal artery stenosis in 2047 patients: a single-center retrospective
      analysis during a 15-year period in China.
AB  - Systematic investigation with large sample size of the distribution of etiologies
      of renal artery stenosis (RAS) is scant in both Western countries and China. We
      retrospectively analyzed the etiology of RAS in 2047 consecutive inpatients
      diagnosed with RAS for hypertension at Fuwai Hospital between 1999 and 2014. The
      number of patients with atherosclerosis was 1668 (81.5%), 259 (12.7%) with
      Takayasu's arteritis (TA), 86 (4.2%) with fibromuscular dysplasia (FMD), 34
      (1.6%) with other causes. There was an obvious increase with age in the
      proportion of atherosclerotic RAS (P<0.001). In patients aged ?40 years (n=319)
      the predominant etiology of RAS was TA (60.5%), followed by FMD (24.8%). In
      patients aged >40 years (n=1728) the major cause of RAS was atherosclerosis
      (94.7%), followed by TA (3.8%).The proportion of TA and FMD in female patients
      was significantly higher than that in male patients (P<0.001). In female patients
      aged ?40 years (n=215), the top three etiologies of RAS were TA (68.4%), FMD
      (27.9%) and atherosclerosis (1.4%). The present analysis showed that
      atherosclerosis, TA and FMD were sequentially the top three causes of RAS in the
      National Center of China. Age and gender had a significant effect on the
      distribution of etiologies of RAS. 

PMID- 25947276
TI  - Mitochondrial and genomic ancestry are associated with etiology of heart failure
      in Brazilian patients.
AB  - There is a high prevalence of heart failure (HF) in the general population, but
      it is more common in black people. We evaluated the association between genomic
      ancestry and mitochondrial haplogroups (mt-haplogroups) with HF etiology in 503
      Brazilian patients. We elicited Mt-haplogroups by analyzing the control region of
      mitochondrial DNA, and genomic ancestry, by using 48 autosomal insertion-deletion
      ancestry informative markers. Hypertensive (28.6%, n=144) and ischemic (28.4%,
      n=143) etiologies of HF were the most prevalent herein. Our results showed that
      233 individuals (46.3%) presented African mitochondrial (mt)-haplogroups, and the
      major contribution in the genomic ancestry analysis was the European ancestry
      (57.5% (+/-22.1%)). African mt-haplogroups were positively associated with a
      diagnosis of hypertensive cardiomyopathy (odds ratio, OR 1.55, confidence
      interval, CI 95% 1.04-2.44, P=0.04) when compared with European mt-haplogroups.
      Regarding the genomic ancestry, the African ancestry variant had higher risks (OR
      7.84, 95% CI 2.81-21.91, P<0.001), whereas the European ancestry variant had
      lower risks (OR 0.14, 95% CI 0.04-5.00, P<0.001) for developing the hypertensive
      etiology. In addition, European ancestry showed an OR of 4.05 (CI 95% 1.53-10.74,
      P=0.005), whereas African ancestry showed an OR of 0.17 (CI 95% 0.06-0.48,
      P=0.001) for developing ischemic etiology. In conclusion, this study supports the
      importance of using ancestry informative markers and mitochondrial DNA to study
      the genetics of complex diseases in admixed populations to improve the
      management, treatment and prevention of these illnesses. Therefore, the ancestry
      informative markers and mt-haplogroups could provide new biomarkers to be
      associated with HF etiologies and be used as a premise for more specific
      management. 

PMID- 25947277
TI  - Molecular dynamics to enhance structure-based virtual screening on cathepsin B.
AB  - Molecular dynamics (MD) and molecular docking are commonly used to study
      molecular interactions in drug discovery. Most docking approaches consider
      proteins as rigid, which can decrease the accuracy of predicted docked poses.
      Therefore MD simulations can be used prior to docking to add flexibility to
      proteins. We evaluated the contribution of using MD together with docking in a
      docking study on human cathepsin B, a well-studied protein involved in numerous
      pathological processes. Using CHARMM biomolecular simulation program and AutoDock
      Vina molecular docking program, we found, that short MD simulations significantly
      improved molecular docking. Our results, expressed with the area under the
      receiver operating characteristic curves, show an increase in discriminatory
      power i.e. the ability to discriminate active from inactive compounds of
      molecular docking, when docking is performed to selected snapshots from MD
      simulations. 

PMID- 25947278
TI  - COmplex coronary Bifurcation lesions: RAndomized comparison of a strategy using a
      dedicated self-expanding biolimus-eluting stent versus a culotte strategy using
      everolimus-eluting stents: primary results of the COBRA trial.
AB  - AIMS: We aimed to compare healing responses with optical coherence tomography,
      and clinical and angiographic outcome after treatment of coronary bifurcation
      lesions with a dedicated stent versus a conventional culotte technique. METHODS
      AND RESULTS: Forty patients with true and complex coronary bifurcation lesions
      were randomly assigned to treatment with the AxxessTM bifurcation stent in the
      proximal main vessel (MV) and additional BioMatrixTM stents in the branches
      (Biosensors Europe SA, Morges, Switzerland), versus a culotte technique using
      XIENCETM stents (Abbott Vascular, Santa Clara, CA, USA). The primary endpoint of
      percentage of uncovered struts at nine months was similar with the dedicated
      strategy vs. culotte in the proximal MV (median 17.8 [IQR 3.3-24.7] vs. 6.8 [2.0
      20.5]; p=0.19), bifurcation core (9.5 [5.7-19.5] vs. 4.0 [0.7-17.6]; p=0.17),
      distal MV (2.6 [2.3-18] vs. 2.2 [0.5-6.0]; p=0.09) and side branch (5.7 [1.5
      11.5] vs. 1.9 [0-5.8]; p=0.14). As compared with culotte, a strategy using Axxess
      resulted in a significantly larger lumen in the proximal MV both acutely (minimum
      lumen diameter 3.03+/-0.51 vs. 2.71+/-0.44 mm, p=0.04) and at follow-up (mean
      lumen area 10.0+/-2.1 vs. 7.1+/-1.8 mm2, p<0.001), and in a lower angiographic
      late lumen loss (p=0.05). Both strategies resulted in good clinical outcomes at
      one year, and no stent thromboses. CONCLUSIONS: As compared with a culotte
      strategy with XIENCE stents, complex bifurcation stenting using a dedicated
      strategy combining Axxess and BioMatrix stents results in similar stent strut
      coverage at nine-month follow-up, and a significantly larger lumen and lower
      angiographic late lumen loss in the proximal MV.

PMID- 25947275
TI  - Non-adherence to antihypertensive medication is very common among resistant
      hypertensives: results of a directly observed therapy clinic.
AB  - Resistant hypertension is common among the hypertensive population with reported
      prevalence of 12 to 15%. These patients have a higher cardiovascular risk and
      consequently a poorer cardiovascular prognosis. Suboptimal adherence with
      antihypertensive medication is a common contributing factor in apparent treatment
      resistant hypertension. Patients were observed taking their medications under
      direct supervision at our directly observed therapy (DOT) clinic. At the DOT
      clinic visit, patients were fitted with a 24-h ambulatory blood pressure (ABP)
      monitor and each drug, at currently prescribed dose, was administered by a nurse;
      at an hourly interval and patient observed for 7 h. ABP readings between pre and
      post DOT clinic were compared. Fifty out of 56 patients had complete data on the
      ABP. Twenty four were female and the mean (s.d.) age was 62.0 (11.0) years. On
      the basis of the study methods that differentiated patients according to their BP
      response during the DOT clinic, twenty-five (50.0%) patients were deemed to be
      truly resistant (24-h ambulatory systolic blood pressure (SBP) fall <5 mm Hg) and
      the remaining 25 were deemed to have clinically significant non-adherence (24-h
      ambulatory SBP fall ?5 mm Hg) to prescribed therapy. In non-adherent patients,
      the mean 24-h ambulatory BP drop observed was 19.5/9.4 mm Hg (P<0.001 for both).
      Our results suggest that non-adherence is very common among patients considered
      to have apparent treatment-resistant hypertension. DOT clinic can be an effective
      method of identifying the truly resistant hypertensive patients. 

PMID- 25947279
TI  - Role of intraprocedural coronary computed tomographic angiography in percutaneous
      coronary intervention of chronic total occlusion.

PMID- 25947280
TI  - Analysis on evolution and research focus in psychiatry field.
AB  - BACKGROUND: With the dramatic rise in mental disorders and mental illnesses,
      psychiatry has become one of the fastest growing clinical medical disciplines.
      This has led to a rise in the number of scientific research papers being
      published in this field. METHODS: We selected research papers in ten psychiatric
      journals that were published during 1983 to 2012. These ten journals were those
      with the top Impact Factor (IF) as indicated by the Science Citation Index
      Expanded (SCI-Expanded). We utilized information visualization software
      (CiteSpace) to conduct co-citation and Hierarchal clustering analysis to map
      knowledge domains to determine the evolution and the foci of research in this
      field. RESULTS: In the evolution of the field of psychiatry, there were four
      stages identified. The result of hierarchal clustering analysis revealed that the
      research foci in the psychiatric field were primarily studies of child and
      adolescent psychiatry, diagnostic and classification criteria, brain imaging and
      molecular genetics. CONCLUSION: The results provide information about the
      evolution and the foci of the research in the field of psychiatry. This
      information can help researchers determine the direction of the research in the
      field of psychiatry; Moreover, this research provides reasonable suggestions to
      guide research in psychiatry field and provide scientific evidence to aid in the
      effective prevention and treatment of mental disorders.

PMID- 25947281
TI  - [The contributions by Emil Kraepelin to the knowledge on sleep disorders and
      their treatment].
AB  - While Emil Kraepelin's comprehensive psychiatric oeuvre has attracted
      researchers' attention, his studies on sleep disorders and their treatment as
      well as on the interconnections between sleep and mental disorders so far seem to
      have been neglected.This article identifies and analyzes Kraepelin's sporadic
      contributions on the pathology of sleep, the comorbidities and treatment made
      between 1883 and 1924 in textbooks and isolated papers as well as in a
      presentation that was also published and compares them with current opinions in
      sleep research.Kraepelin never published a dedicated work on sleep, apart from a
      summary of the different narcotics; however, his occasional statements reveal
      astonishing insights and in particular his clear etiologically oriented
      classification of sleep disorders is captivating. Similar to the current
      classification, Kraepelin conceptualized sleep disorders as symptoms or rather a
      complex of symptoms and also identified associated diseases which once again are
      very near to current opinion. Apart from this his recommendations on sleep
      hygiene and, in a second step, pharmacological treatment of pathological sleep
      patterns are still clinically relevant. As early as the end of the nineteenth
      century Kraepelin laid down an algorithm of treatment which is very similar to
      the current clinical guidelines. At Kraepelin's time it seemed impossible to
      reach an agreement on classification and treatment issues of sleep disturbances
      and even though there has been an ongoing discussion until the present day, an
      agreement at least about guidelines could be reached. Against this background
      Kraepelin's contributions can still be regarded as a proposal for best practice. 

PMID- 25947282
TI  - Microwave spectroscopy of the low-filling-factor bilayer electron solid in a wide
      quantum well.
AB  - At the low Landau filling factor termination of the fractional quantum Hall
      effect series, two-dimensional electron systems exhibit an insulating phase that
      is understood as a form of pinned Wigner solid. Here we use microwave
      spectroscopy to probe the transition to the insulator for a wide quantum well
      sample that can support single-layer or bilayer states depending on its overall
      carrier density. We find that the insulator exhibits a resonance which is
      characteristic of a bilayer solid. The resonance also reveals a pair of
      transitions within the solid, which are not accessible to dc transport
      measurements. As density is biased deeper into the bilayer solid regime, the
      resonance grows in specific intensity, and the transitions within the insulator
      disappear. These behaviours are suggestive of a picture of the insulating phase
      as an emulsion of liquid and solid components. 

PMID- 25947283
TI  - Prognostic indicators of lenalidomide for multiple myeloma: consensus and
      controversy.
AB  - The long-term outcome of multiple myeloma (MM) has been greatly improved through
      new agents, one being lenalidomide (LEN). Based upon the findings of in vitro
      experiments, its mode of action against MM occurs through a combination of direct
      tumoricidal effects on myeloma cells, modulatory effects on tumor immunity and
      tumor microenvironment-regulatory effects. However, it has not been clearly
      defined whether the clinical response and long-term outcome of MM with LEN
      treatment truly reflect the mechanisms of action of LEN proposed by in vitro
      studies. To ascertain what is known and what remains to be elucidated with LEN,
      we review the current literature on the mode of action of LEN in association with
      myeloma pathophysiology, and discuss the prognostic indicators in the treatment
      of MM with LEN. 

PMID- 25947284
TI  - The prognostic significance of lymphovascular invasion in patients with
      resectable gastric cancer: a large retrospective study from Southern China.
AB  - BACKGROUND: The focus of this study was to assess the impact of lymphovascular
      invasion (LVI) on both the recurrence of cancer and the long-term survival of
      Chinese patients with resectable gastric cancer (GC). METHODS: A retrospective
      analysis of the clinicopathological data for 1148 GC patients who had undergone
      gastrectomy with regional lymphadenectomy was performed. The primary objective
      was to assess the correlation between LVI and post-surgery outcomes for each
      patient. This was done by routine H & E staining for LVI on patients' disease
      free survival (DFS) and disease-specific survival (DSS). RESULTS: LVI was
      detected in 404 (35.2%) of the 1148 GC patients. The presence of LVI was
      significantly correlated with the level of CA19-9, the tumor size, the Lauren
      classification, tumor differentiation, gastric wall invasive depth, lymph node
      involvement, distant metastasis and an advanced TNM stage. There was a lower DFS
      and DSS in the patients with LVI as compared to the patients without LVI. A
      multivariate analysis also identified LVI as an independent prognostic factor of
      both DSS and DFS. CONCLUSIONS: The presence of LVI is a risk factor for the
      recurrence of cancer and an independent indicator of a poor outcome in GC
      patients following surgery. The LVI status should be taken into consideration
      when determining the best approach for the treatment of the individual.

PMID- 25947286
TI  - BCNU wafer placement with temozolomide (TMZ) in the immediate postoperative
      period after tumor resection followed by radiation therapy with TMZ in patients
      with newly diagnosed high grade glioma: final results of a prospective, multi
      institutional, phase II trial.
AB  - Temozolomide (TMZ) and BCNU have demonstrated anti-glioma synergism in
      preclinical models. We report final data from a prospective, multi-institutional
      study of BCNU wafers and early TMZ followed by radiation therapy with TMZ in
      patients with newly diagnosed malignant glioma. 65 patients were consented in 4
      institutions, and 46 patients (43 GBM, 3 AA) were eligible for analysis. After
      resection and BCNU wafer placement, TMZ began on day four postoperatively.
      Radiation and TMZ (RT/TMZ) were then administered, followed by monthly TMZ at 200
      mg/m2 for the first 26 patients, which was reduced to 150 mg/m2 for the remaining
      20 patients. Non-hematologic toxicities were minimal. Nine of 27 patients (33 %)
      who received 200 mg/m2 TMZ, but only 1 of 20 (5 %) who received 150 mg/m2,
      experienced grade 3/4 thrombocytopenia. Median progression free survival (PFS)
      and overall survival (OS) period was 8.5 and 18 months, respectively. The 1-year
      OS rate was 76 %, which is a significant improvement compared with the historical
      control 1-year OS rate of 59 % (p = 0.023). However, there was no difference in 1
      year OS compared with standard RT/TMZ (p = 0.12) or BCNU wafer followed by RT/TMZ
      (p = 0.87) in post hoc analyses. Early post-operative TMZ can be safely
      administered with BCNU wafers following resection of malignant glioma at the 150
      mg/m2 dose level. Although there was an OS benefit compared to historical
      control, there was no indication of benefit for BCNU wafers and early TMZ in
      addition to standard RT/TMZ or early TMZ in addition to regimens of BCNU wafers
      followed by RT/TMZ.

PMID- 25947287
TI  - Which one is a valuable surrogate for predicting survival between Tomita and
      Tokuhashi scores in patients with spinal metastases? A meta-analysis for
      diagnostic test accuracy and individual participant data analysis.
AB  - This study is to estimate the diagnostic accuracy of Tokuhashi and Tomita scores
      that assures 6-month predicting survival regarded as a standard of surgical
      treatment. We searched PubMed, EMBASE, European PubMed central, and the Cochrane
      library for papers about the sensitivities and specificities of the Tokuhashi
      and/or Tomita scores to estimate predicting survival. Studies with cut-off values
      of >=9 for Tokuhashi and <=7 for Tomita scores based on prior studies were
      enrolled. Sensitivity, specificity, diagnostic odds ratio (DOR), area under the
      curve (AUC), and the best cut-off value were calculated via meta-analysis and
      individual participant data analysis. Finally, 22 studies were enrolled in the
      meta-analysis, and 1095 patients from 8 studies were included in the individual
      data analysis. In the meta-analysis, the pooled sensitivity/specificity/DOR for 6
      month survival were 57.7 %/76.6 %/4.70 for the Tokuhashi score and 81.8 %/47.8
      %/4.93 for Tomita score. The AUC of summary receiver operating characteristic
      plots was 0.748 for the Tokuhashi score and 0.714 for the Tomita score. Although
      Tokuhashi score was more accurate than Tomita score slightly, both showed low
      accuracy to predict 6 months residual survival. Moreover, the best cut-off values
      of Tokuhashi and Tomita scores were 8 and 6, not 9 and 7, for predicting 6-month
      survival, respectively. Estimation of 6-month predicting survival to decide
      surgery in patients with spinal metastasis is quite limited by using Tokuhashi
      and Tomita scores alone. Tokuhashi and Tomita scores could be incorporated as
      part of a multidisciplinary approach or perhaps interpreted in the context of a
      multidisciplinary approach.

PMID- 25947288
TI  - Challenges in early clinical drug development for ischemia-reperfusion injury in
      kidney transplantation.
AB  - INTRODUCTION: In an effort to expand the donor pool, kidneys from donation after
      cardiac death (DCD) donors are increasingly utilised in renal transplantation.
      These kidneys suffer greater ischemia-reperfusion injury (IRI) and have a higher
      incidence of delayed graft function. In the last 25 years, relatively few
      pharmacological therapies to reduce IRI have been tested in randomised controlled
      trials in renal transplantation and currently no pharmacological agents are
      routinely utilised for this purpose. AREAS COVERED: The authors look at why
      promising treatments in pre-clinical studies have not translated to significant
      clinical benefit in human trials. This may reflect a translational disconnect
      between the pre-clinical models used and clinical problems that are encountered
      in the transplant population. They also discuss the issues in conducting clinical
      trials and its implication on drug development. EXPERT OPINION: Translating
      pharmacological strategies for reducing IRI is highly challenging at every stage
      of development from pre-clinical studies to clinical trials. Scientific knowledge
      of the complexity of IRI is rapidly evolving and new treatments are expected to
      emerge. There are ethical barriers that prevent donor treatments, particularly in
      the DCD setting. However, new clinical techniques such as normothermic regional
      and ex-vivo perfusion represent exciting opportunities to utilise pharmacological
      agents earlier in the process of transplantation.

PMID- 25947291
TI  - Contribution of a low-barrier hydrogen bond to catalysis is not significant in
      ketosteroid isomerase.
AB  - Low-barrier hydrogen bonds (LBHBs) have been proposed to have important
      influences on the enormous reaction rate increases achieved by many enzymes.
      Delta(5)-3-ketosteroid isomerase (KSI) catalyzes the allylic isomerization of
      Delta(5)-3-ketosteroid to its conjugated Delta(4)-isomers at a rate that
      approaches the diffusion limit. Tyr14, a catalytic residue of KSI, has been
      hypothesized to form an LBHB with the oxyanion of a dienolate steroid
      intermediate generated during the catalysis. The unusual chemical shift of a
      proton at 16.8 ppm in the nuclear magnetic resonance spectrum has been attributed
      to an LBHB between Tyr14 Oeta and C3-O of equilenin, an intermediate analogue, in
      the active site of D38N KSI. This shift in the spectrum was not observed in
      Y30F/Y55F/D38N and Y30F/Y55F/Y115F/D38N mutant KSIs when each mutant was
      complexed with equilenin, suggesting that Tyr14 could not form LBHB with the
      intermediate analogue in these mutant KSIs. The crystal structure of
      Y30F/Y55F/Y115F/D38N-equilenin complex revealed that the distance between Tyr14
      Oeta and C3-O of the bound steroid was within a direct hydrogen bond. The
      conversion of LBHB to an ordinary hydrogen bond in the mutant KSI reduced the
      binding affinity for the steroid inhibitors by a factor of 8.1-11. In addition,
      the absence of LBHB reduced the catalytic activity by only a factor of 1.7-2.
      These results suggest that the amount of stabilization energy of the reaction
      intermediate provided by LBHB is small compared with that provided by an ordinary
      hydrogen bond in KSI. 

PMID- 25947292
TI  - PLGA-Loaded Gold-Nanoparticles Precipitated with Quercetin Downregulate HDAC-Akt
      Activities Controlling Proliferation and Activate p53-ROS Crosstalk to Induce
      Apoptosis in Hepatocarcinoma Cells.
AB  - Controlled release of medications remains the most convenient way to deliver
      drugs. In this study, we precipitated gold nanoparticles with quercetin. We
      loaded gold-quercetin into poly(DL-lactide-co-glycolide) nanoparticles (NQ) and
      tested the biological activity of NQ on HepG2 hepatocarcinoma cells to acquire
      the sustained release property. We determined by circular dichroism spectroscopy
      that NQ effectively caused conformational changes in DNA and modulated different
      proteins related to epigenetic modifications and cell cycle control. The
      mitochondrial membrane potential (MMP), reactive oxygen species (ROS), cell
      cycle, apoptosis, DNA damage, and caspase 3 activity were analyzed by flow
      cytometry, and the expression profiles of different anti- and pro-apoptotic as
      well as epigenetic signals were studied by immunoblotting. A cytotoxicity assay
      indicated that NQ preferentially killed cancer cells, compared to normal cells.
      NQ interacted with HepG2 cell DNA and reduced histone deacetylases to control
      cell proliferation and arrest the cell cycle at the sub-G stage. Activities of
      cell cycle-related proteins, such as p21(WAF), cdk1, and pAkt, were modulated. NQ
      induced apoptosis in HepG2 cells by activating p53-ROS crosstalk and induces
      epigenetic modifications leading to inhibited proliferation and cell cycle
      arrest.

PMID- 25947290
TI  - Resolving complex chromosome structures during meiosis: versatile deployment of
      Smc5/6.
AB  - The Smc5/6 complex, along with cohesin and condensin, is a member of the
      structural maintenance of chromosome (SMC) family, large ring-like protein
      complexes that are essential for chromatin structure and function. Thanks to
      numerous studies of the mitotic cell cycle, Smc5/6 has been implicated to have
      roles in homologous recombination, restart of stalled replication forks,
      maintenance of ribosomal DNA (rDNA) and heterochromatin, telomerase-independent
      telomere elongation, and regulation of chromosome topology. The nature of these
      functions implies that the Smc5/6 complex also contributes to the profound
      chromatin changes, including meiotic recombination, that characterize meiosis.
      Only recently, studies in diverse model organisms have focused on the potential
      meiotic roles of the Smc5/6 complex. Indeed, Smc5/6 appears to be essential for
      meiotic recombination. However, due to both the complexity of the process of
      meiosis and the versatility of the Smc5/6 complex, many additional meiotic
      functions have been described. In this review, we provide a clear overview of the
      multiple functions found so far for the Smc5/6 complex in meiosis. Additionally,
      we compare these meiotic functions with the known mitotic functions in an attempt
      to find a common denominator and thereby create clarity in the field of Smc5/6
      research. 

PMID- 25947294
TI  - Enhanced oxygen consumption in Herbaspirillum seropedicae fnr mutants leads to
      increased NifA mediated transcriptional activation.
AB  - BACKGROUND: Orthologous proteins of the Crp/Fnr family have been previously
      implicated in controlling expression and/or activity of the NifA transcriptional
      activator in some diazotrophs. This study aimed to address the role of three Fnr
      like proteins from H. seropedicae SmR1 in controlling NifA activity and
      consequent NifA-mediated transcription activation. RESULTS: The activity of NifA
      dependent transcriptional fusions (nifA::lacZ and nifB::lacZ) was analysed in a
      series of H. seropedicae fnr deletion mutant backgrounds. We found that combined
      deletions in both the fnr1 and fnr3 genes lead to higher expression of both the
      nifA and nifB genes and also an increased level of nifH transcripts. Expression
      profiles of nifB under different oxygen concentrations, together with oxygen
      consumption measurements suggest that the triple fnr mutant has higher
      respiratory activity when compared to the wild type, which we believe to be
      responsible for greater stability of the oxygen sensitive NifA protein. This
      conclusion was further substantiated by measuring the levels of NifA protein and
      its activity in fnr deletion strains in comparison with the wild-type.
      CONCLUSIONS: Fnr proteins are indirectly involved in controlling the activity of
      NifA in H. seropedicae, probably as a consequence of their influence on
      respiratory activity in relation to oxygen availability. Additionally we can
      suggest that there is some redundancy in the physiological function of the three
      Fnr paralogs in this organism, since altered respiration and effects on NifA
      activity are only observed in deletion strains lacking both fnr1 and fnr3.

PMID- 25947293
TI  - STING Negatively Regulates Double-Stranded DNA-Activated JAK1-STAT1 Signaling via
      SHP-1/2 in B Cells.
AB  - Recognition of cytosolic DNA initiates a series of innate immune responses by
      inducing IFN-I production and subsequent triggering JAK1-STAT1 signaling which
      plays critical roles in the pathogenesis of infection, inflammation and
      autoimmune diseases through promoting B cell activation and antibody responses.
      The stimulator of interferon genes protein (STING) has been demonstrated to be a
      critical hub of type I IFN induction in cytosolic DNA-sensing pathways. However,
      it still remains unknown whether cytosolic DNA can directly activate the JAK1
      STAT1 signaling or not. And the role of STING is also unclear in this response.
      In the present study, we found that dsDNA directly triggered the JAK1-STAT1
      signaling by inducing phosphorylation of the Lyn kinase. Moreover, this response
      is not dependent on type I IFN receptors. Interestingly, STING could inhibit
      dsDNA-triggered activation of JAK1-STAT1 signaling by inducing SHP-1 and SHP-2
      phosphorylation. In addition, compared with normal B cells, the expression of
      STING was significantly lower and the phosphorylation level of JAK1 was
      significantly higher in B cells from MRL/lpr lupus-prone mice, highlighting the
      close association between STING low-expression and JAK1-STAT1 signaling
      activation in B cells in autoimmune diseases. Our data provide a molecular
      insight into the novel role of STING in dsDNA-mediated inflammatory disorders. 

PMID- 25947295
TI  - Lower serum magnesium concentration is associated with diabetes, insulin
      resistance, and obesity in South Asian and white Canadian women but not men.
AB  - BACKGROUND: A large proportion of adults in North America are not meeting
      recommended intakes for magnesium (Mg). Women and people of South Asian race may
      be at higher risk for Mg deficiency because of lower Mg intakes relative to
      requirements and increased susceptibility to diabetes, respectively. OBJECTIVE:
      This study compared serum Mg concentrations in South Asian (n=276) and white
      (n=315) Canadian women and men aged 20-79 years living in Canada's Capital Region
      and examined the relationship with diabetes, glucose control, insulin resistance,
      and body mass index. RESULTS: Serum Mg concentration was lower in women of both
      races and South Asians of both genders. Racial differences in serum Mg were not
      significant after controlling for use of diabetes medication. A substantial
      proportion of South Asian (18%) and white (9%) women had serum Mg <0.75 mmol/L
      indicating hypomagnesemia. Use of diabetes medication and indicators of poorer
      glucose control, insulin resistance, and obesity were associated with lower serum
      Mg in women, but not in men. CONCLUSIONS: These results suggest that the higher
      incidence of diabetes in South Asians increases their risk for Mg deficiency and
      that health conditions that increase Mg requirements have a greater effect on Mg
      status in women than men.

PMID- 25947297
TI  - Identification of a gene cluster associated with triclosan catabolism.
AB  - Aerobic degradation of bis-aryl ethers like the antimicrobial triclosan typically
      proceeds through oxygenase-dependent catabolic pathways. Although several studies
      have reported on bacteria capable of degrading triclosan aerobically, there are
      no reports describing the genes responsible for this process. In this study, a
      gene encoding the large subunit of a putative triclosan oxygenase, designated
      tcsA was identified in a triclosan-degrading fosmid clone from a DNA library of
      Sphingomonas sp. RD1. Consistent with tcsA's similarity to two-part dioxygenases,
      a putative FMN-dependent ferredoxin reductase, designated tcsB was found
      immediately downstream of tcsA. Both tcsAB were found in the midst of a putative
      chlorocatechol degradation operon. We show that RD1 produces hydroxytriclosan and
      chlorocatechols during triclosan degradation and that tcsA is induced by
      triclosan. This is the first study to report on the genetics of triclosan
      degradation.

PMID- 25947296
TI  - Relative validity and reliability of a quantitative food frequency questionnaire
      for adults in Guam.
AB  - BACKGROUND: Guam is a US territory in the western Pacific with a diverse
      population that includes understudied ethnic groups such as Chamorros and
      Filipinos. A food frequency questionnaire (FFQ) to estimate dietary intake was
      needed to facilitate studies of diet and health among adults living in Guam.
      OBJECTIVE: To develop and validate an FFQ to assess dietary intake over a 1-year
      period among adult Guam residents. DESIGN: A three-part study was conducted: 1)
      an initial cross-sectional study using 24-h recalls to identify a food and
      beverage list for the FFQ and resulting in a final FFQ containing 142 food and
      drink items; 2) to test reliability, 56 different individuals completed the FFQ
      twice; and 3) to test relative validity, self-administered FFQs and up to 2 days
      of food record data from an additional 109 individuals were collected, and daily
      nutrient intake from the two methods was compared. RESULTS: The reliability of
      the FFQ was very good (rho range=0.65-0.75), and the relative validity of the FFQ
      was good for women (median Spearman's correlation [rho] between instruments of
      0.45 across 20 nutrients and an interquartile range [IQR] of 0.42-0.58) and
      generally adequate for men (median rho=0.31, IQR=0.23-0.55). Validity was also
      good for Chamorros (median rho=0.47, IQR=0.38-0.53) and generally adequate for
      Filipinos (median rho=0.42, IQR=0.20-0.62). Correlations after energy adjustment
      were lower (overall median rho=0.20, IQR=0.14-0.26). CONCLUSIONS: The FFQ can be
      used to rank nutrient intake for adults in Guam and may be helpful in the
      analysis of relationships between diet and chronic disease in Guam.

PMID- 25947298
TI  - Preoperative endoscopic tattooing to mark the tumour site does not improve lymph
      node retrieval in colorectal cancer: a retrospective cohort study.
AB  - BACKGROUND: A direct correlation between number of lymph nodes retrieved and
      evaluated after a colectomy for colorectal cancer and survival of the patient has
      been reported, and consensus guidelines recommend to assess at least 12 lymph
      nodes for adequate staging. Many factors (i.e., patients' and tumour
      characteristics, surgeon, and pathologist) may influence the evaluation of the
      presence of neoplastic disease in lymph nodes as well as the total number of
      lymph nodes examined. Preoperative endoscopic tattooing to mark the site of the
      tumour has recently been suggested to facilitate the retrieval of lymph nodes in
      colorectal specimens. The aim of this study was to investigate its association
      with adequate lymphadenectomy (>=12 nodes) after colorectal resection for cancer.
      RESULTS: All patients undergoing elective colorectal resection for cancer between
      2009 and 2011 at the S. Anna University Hospital in Ferrara, Italy (N = 250) were
      retrospectively divided into two cohorts according to whether ink tattooing to
      mark the tumour site was performed during preoperative colonoscopy. The two
      cohorts were comparable regarding age, gender, body mass index, tumour location
      and size, TNM staging, and DNA microsatellite instability-high status. No
      difference between the tattoo (N = 107) and control (N = 143) groups could be
      detected in the rate of adequate lymphadenectomies performed (78% vs. 79%, p =
      0.40). All factors known to influence lymph nodes retrieval from colorectal
      specimen were specifically evaluated. Rectal and colonic cancers were analysed
      together and separately. Full adjusted logistic regression analysis in patients
      who underwent colonic resection showed that right hemicolectomy (OR 4.72; CI95%
      1.09-20.36) was the only factor associated to adequate lymphadenectomy. No
      association between ink tattooing performed preoperatively to mark the site of
      the tumour and adequate lymphadenectomy after colorectal resection was found with
      logistic regression analysis. CONCLUSION: This study shows that preoperative ink
      tattooing utilized to mark the site of the tumour does not improve adequate
      lymphadenectomy and lymph nodes yield from colorectal cancer specimens. Further
      studies are therefore needed to determine if preoperative colonoscopic tattooing
      to mark the tumour site can refine staging.

PMID- 25947299
TI  - PR2ALIGN: a stand-alone software program and a web-server for protein sequence
      alignment using weighted biochemical properties of amino acids.
AB  - BACKGROUND: Alignment of amino acid sequences is the main sequence comparison
      method used in computational molecular biology. The selection of the amino acid
      substitution matrix best suitable for a given alignment problem is one of the
      most important decisions the user has to make. In a conventional amino acid
      substitution matrix all elements are fixed and their values cannot be easily
      adjusted. Moreover, most existing amino acid substitution matrices account for
      the average (dis)similarities between amino acid types and do not distinguish the
      contribution of a specific biochemical property to these (dis)similarities.
      FINDINGS: PR2ALIGN is a stand-alone software program and a web-server that
      provide the functionality for implementing flexible user-specified alignment
      scoring functions and aligning pairs of amino acid sequences based on the
      comparison of the profiles of biochemical properties of these sequences. Unlike
      the conventional sequence alignment methods that use 20x20 fixed amino acid
      substitution matrices, PR2ALIGN uses a set of weighted biochemical properties of
      amino acids to measure the distance between pairs of aligned residues and to find
      an optimal minimal distance global alignment. The user can provide any number of
      amino acid properties and specify a weight for each property. The higher the
      weight for a given property, the more this property affects the final alignment.
      We show that in many cases the approach implemented in PR2ALIGN produces better
      quality pair-wise alignments than the conventional matrix-based approach.
      CONCLUSIONS: PR2ALIGN will be helpful for researchers who wish to align amino
      acid sequences by using flexible user-specified alignment scoring functions based
      on the biochemical properties of amino acids instead of the amino acid
      substitution matrix. To the best of the authors' knowledge, there are no existing
      stand-alone software programs or web-servers analogous to PR2ALIGN. The software
      is freely available from http://pr2align.rit.albany.edu.

PMID- 25947300
TI  - EMA will restrict experts' role in drug assessment if they plan to work for
      industry.

PMID- 25947303
TI  - Unassisted HI photoelectrolysis using n-WSe2 solar absorbers.
AB  - Molybdenum and tungsten diselenide are among the most robust and efficient
      semiconductor materials for photoelectrochemistry, but they have seen limited use
      for integrated solar energy storage systems. Herein, we report that n-type WSe2
      photoelectrodes can facilitate unassisted aqueous HI electrolysis to H2(g) and
      HI3(aq) when placed in contact with a platinum counter electrode and illuminated
      by simulated sunlight. Even in strongly acidic electrolyte, the photoelectrodes
      are robust and operate very near their maximum power point. We have rationalized
      this behavior by characterizing the n-WSe2|HI/HI3 half cell, the
      Pt|HI/H2||HI3/HI|Pt full cell, and the n-WSe2 band-edge positions. Importantly,
      specific interactions between the n-WSe2 surface and aqueous iodide significantly
      shift the semiconductor's flatband potential and allow for unassisted HI
      electrolysis. These findings exemplify the important role of interfacial chemical
      reactivity in influencing the energetics of semiconductor-liquid junctions and
      the resulting device performance. 

PMID- 25947301
TI  - From hypertension control to global cardiovascular risk management: an
      educational intervention in a cluster-randomised controlled trial.
AB  - BACKGROUND: Guidelines on hypertension management recommend adjusting therapeutic
      efforts in accordance with global cardiovascular risk (CVR) rather than by blood
      pressure levels alone. However, this paradigm change has not yet arrived in
      German General Practice. We have evaluated the effect of an educational outreach
      visit with general practitioners (GPs), encouraging them to consider CVR in
      treatment decisions for patients with hypertension. METHODS: Prospective cluster
      randomised trial comprising 3443 patients with known hypertension treated by 87
      GPs. Practices were randomly assigned to complex (A) or simple (B) intervention.
      Both groups received a guideline by mail; group A also received complex peer
      intervention promoting the concept of global CVR. Clinical data were collected at
      baseline and 6-9 months after intervention. Main outcome was improvement of
      calculated CVR in the predefined subpopulation of patients with a high CVR (10
      year mortality >=5%), but no manifest cardiovascular disease. RESULTS: Adjusted
      for baseline the follow-up CVR were 13.1% (95% CI 12.6%-13.6%) (A) and 12.6% (95%
      CI 12.2%-13.1%) (B) with a group difference (A vs. B) of 0.5% (-0.2%-1.1%), p =
      0.179. The group difference was -0.05% in patients of GPs familiar with global
      CVR and 1.1% in patients of GPs not familiar with with global CVR. However, this
      effect modification was not significant (p = 0.165). Pooled over groups, the
      absolute CVR reduction from baseline was 1.0%, p < 0.001. The ICC was 0.026 (p =
      0.002). Hypertension control (BP <140/90 mmHg) improved in the same subpopulation
      from 38.1 to 45.9% in the complex intervention group, and from 35.6 to 46.5% in
      the simple intervention group, with adjusted follow-up control rates of 46.7%
      (95% CI 40.4%-53.1%) (A) and 46.9% (95% CI 40.3%-53.5% (B) and an adjusted odds
      ratio (A vs B) of 0.99 (95% CI 0.68-1.45), p = 0.966. CONCLUSIONS: Our complex
      educational intervention, including a clinical outreach visit, had no significant
      effect on CVR of patients with known hypertension at high risk compared to a
      simple postal intervention. TRIAL REGISTRATION: ISRCTN44478543 .

PMID- 25947302
TI  - Variability in screening prevention activities in primary care in Spain: a
      multilevel analysis.
AB  - BACKGROUND: Despite evidence of the benefits of prevention activities, studies
      have reported only partial integration and great variability of screening in
      daily clinical practice. The study objectives were: 1) To describe Primary Health
      Care (PHC) screening for arterial hypertension, dyslipidaemia, obesity, tobacco
      use, and excessive alcohol consumption in 2008 in 2 regions of Spain, based on
      electronic health records, and 2) To assess and quantify variability in
      screening, and identify factors (of patient, general practitioners and PHC team)
      associated with being screened, that are common throughout the PHC population.
      METHODS: Multicentre, cross-sectional study of individuals aged >= 16 years (N =
      468,940) who visited the 426 general practitioners (GPs) in 44 PHC teams in
      Catalonia and Navarre in 2008. OUTCOMES: screening for hypertension,
      dyslipidaemia, obesity, tobacco use, and excessive alcohol consumption. Other
      variables were considered at the individual (sociodemographics, visits, health
      problems), GP and PHC team (region among others). Individual and contextual
      factors associated with the odds of being screened and the variance attributable
      to each level were identified using the SAS PROC GLIMMIX macro. RESULTS: The most
      prevalent screenings were for dyslipidaemia (64.4%) and hypertension (50.8%); the
      least prevalent was tobacco use (36.6%). Overall, the odds of being screened were
      higher for women, older patients, those with more comorbidities, more
      cardiovascular risk factors, and more frequent office visits, and those assigned
      to a female GP, a GP with a lower patient load, or a PHC team with a lower
      percentage of patients older than 65 years. On average, individuals in Navarre
      were less likely to be screened than those in Catalonia. Hypertension and
      dyslipidaemia screenings had the least unexplained variability between PHC teams
      and GPs, respectively, after adjusting for individual and contextual factors.
      CONCLUSIONS: Of the studied screenings, those for obesity, tobacco, and alcohol
      use were the least prevalent. Attention to screening, especially for tobacco and
      alcohol, can be greatly improved in the PHC setting.

PMID- 25947304
TI  - Performance analysis of the beam shaping method on optical auditory neural
      stimulation in vivo.
AB  - Previous research has shown that infrared neural stimulation (INS) could be an
      alternative approach to evoke auditory neural activities. The laser beam property
      of the fiber output is a considerable aspect of INS, and the corresponding
      effects on auditory responses in vivo deserve further discussions. The paper
      presents a beam-shaped infrared laser stimulation method of auditory nerves.
      Pulsed 980-nm fiber-coupled laser systems were used as the radiant sources. The
      gradient reflective index (GRIN) lens was added at the port of the optical fiber
      as a beam shaping structure. The laser spot sizes and properties between the beam
      shaped output and the bare fiber output were preliminarily analyzed by a laser
      beam profiler. And further experiments in vivo with four deafened adult guinea
      pigs were conducted. Optically evoked auditory brainstem responses (OABRs) of the
      animal samples were recorded and compared under the two output configurations.
      The results show a decrease of the beam divergence compared to a bare output
      fiber, and the INS with a beam shaping design evokes above 13 % increase on OABR
      amplitudes than the bare fiber output, especially when enlarging the distance
      between the optical fiber and the nerve tissue. The beam shaping design can
      enhance the effect of INS for evoking auditory nerves, and it could be an
      optimized design in the future implementation of optical cochlear implants. 

PMID- 25947305
TI  - A giant polymer lattice in a polymer-stabilized blue phase liquid crystal.
AB  - Ultrasmall-angle synchrotron X-ray scattering measurements showed that a three
      dimensional polymer lattice of a few 100 nm order with body-centered cubic O(8-)
      symmetry was formed in a polymer-stabilized blue phase liquid crystal. We
      obtained clear experimental evidence that the polymer chains condensed
      selectively in the disclinations within the blue phase during photo
      polymerization of monomers in the blue phase. 

PMID- 25947306
TI  - Tuberculous bronchonodal fistula in adult patients: CT findings.
AB  - PURPOSE: To describe the computed tomography (CT) findings of bronchonodal
      fistulas occurring in seven adult patients with active pulmonary tuberculosis
      (TB). MATERIALS AND METHODS: Seven patients with confirmed tuberculous
      bronchonodal fistula who underwent chest CT scans were enrolled. The patient
      demographics and CT and bronchoscopic findings were analyzed. The bronchonodal
      fistula site, distribution and characteristics of the involved lymph nodes,
      airway change, and parenchymal lesions found on CT were reviewed. RESULTS: The
      seven patients comprised four males and three females. All patients were over 70
      years old (range 72-85 years; mean age 78 years). The site of occurrence of the
      bronchonodal fistula was on the right side between the lobar bronchi and
      paratracheal or hilar lymph nodes in five patients and on the left side between
      the left main bronchus and subcarinal lymph nodes in two patients. The involved
      lymph nodes were necrotic in four patients and necrotic with partial
      calcification in three. In all patients, active pulmonary TB lesions involving
      multiple lobes were found as consolidations (n = 3), poorly defined nodules (n =
      4), cavities (n = 1), or centrilobular nodules exhibiting tree-in-bud appearance
      (n = 7). CONCLUSION: Bronchonodal fistula can occur as a complication of active
      pulmonary TB with TB lymphadenitis in adult patients, especially in the elderly.
      The fistulas usually involved the right side. The lobar bronchus was frequently
      involved on the right side and the main bronchus on the left side.

PMID- 25947307
TI  - Renal cell carcinomas with t(6;11) (p21;q12): presentation of two cases with
      computed tomography findings.
AB  - Renal cell carcinomas with t(6;11) (p21;q12) translocation are extremely rare and
      primarily affect children and young adults. To our knowledge, there has been no
      case report focusing on the imaging manifestations in the existing literature.
      Hence, we describe the computed tomography findings of two young adults. 

PMID- 25947308
TI  - Comment on Schwartz, J.; Dockery, D.W.; Neas, M.L. 1996. Is daily mortality
      associated specifically with fine particles?; J. Air Waste Manage. Assoc. 46: 927
      939.

PMID- 25947309
TI  - Response to comments by Mage regarding "Is daily mortality associated
      specifically with fine particles?".

PMID- 25947310
TI  - Introduction to JA&WMA Special Issue on Air Quality and Human Health.

PMID- 25947311
TI  - Health benefits of air pollution abatement policy: Role of the shape of the
      concentration-response function.
AB  - There is strong evidence that fine particulate matter (aerodynamic diameter<2.5
      MUm; PM2.5) air pollution contributes to increased risk of disease and death.
      Estimates of the burden of disease attributable to PM2.5 pollution and benefits
      of reducing pollution are dependent upon the shape of the concentration response
      (C-R) functions. Recent evidence suggests that the C-R function between PM2.5 air
      pollution and mortality risk may be supralinear across wide ranges of exposure.
      Such results imply that incremental pollution abatement efforts may yield greater
      benefits in relatively clean areas than in highly polluted areas. The role of the
      shape of the C-R function in evaluating and understanding the costs and health
      benefits of air pollution abatement policy is explored. There remain
      uncertainties regarding the shape of the C-R function, and additional efforts to
      more fully understand the C-R relationships between PM2.5 and adverse health
      effects are needed to allow for more informed and effective air pollution
      abatement policies. Current evidence, however, suggests that there are benefits
      both from reducing air pollution in the more polluted areas and from continuing
      to reduce air pollution in cleaner areas. IMPLICATIONS: Estimates of the benefits
      of reducing PM2.5 air pollution are highly dependent upon the shape of the PM2.5
      mortality concentration-response (C-R) function. Recent evidence indicates that
      this C-R function may be supralinear across wide ranges of exposure, suggesting
      that incremental pollution abatement efforts may yield greater benefits in
      relatively clean areas than in highly polluted areas. This paper explores the
      role of the shape of the C-R function in evaluating and understanding the costs
      and health benefits of PM2.5 air pollution abatement.

PMID- 25947313
TI  - Particulate matter components, sources, and health: Systematic approaches to
      testing effects.
AB  - Exposure to particulate matter (PM) is associated with adverse health outcomes.
      There has long been a question as to whether some components of the PM mixture
      are of greater public health concern than others so that the sources that emit
      the more toxic components could be controlled. In this paper, we describe the
      National Particle Component Toxicity (NPACT) initiative, a comprehensive research
      program that combined epidemiologic and toxicologic approaches to evaluate this
      critical question, partly relying on information from a national network of air
      quality monitors that provided data on speciated PM2.5 (PM with an aerodynamic
      diameter<2.5 MUm) starting in 2000. We also consider the results of the NPACT
      program in the context of selected research on PM components and health in order
      to assess the current state of the field. Overall, the ambitious NPACT research
      program found associations of secondary sulfate and, to a somewhat lesser extent,
      traffic sources with health effects. Although this and other research has linked
      a variety of health effects to multiple groups of PM components and sources of
      PM, the collective evidence has not yet isolated factors or sources that would be
      closely and unequivocally more strongly related to specific health outcomes. If
      greater success is to be achieved in isolating the effects of pollutants from
      mobile and other major sources, either as individual components or as a mixture,
      more advanced approaches and additional measurements will be needed so that
      exposure at the individual or population level can be assessed more accurately.
      Enhanced understanding of exposure and health effects is needed before it can be
      concluded that regulations targeting specific sources or components of PM2.5 will
      protect public health more effectively than continuing to follow the current
      practices of targeting PM2.5 mass as a whole. IMPLICATIONS: This paper describes
      a comprehensive epidemiologic and toxicologic research program to evaluate
      whether some components and sources of PM may be more toxic than others. This
      question is important for regulatory agencies in setting air quality standards to
      protect people's health. The results show that PM from coal and oil combustion
      and from traffic sources was associated with adverse health outcomes, but other
      components and sources could not definitively be ruled out. Thus, given current
      knowledge, the current practice of setting air quality standards for PM mass as a
      whole likely remains an effective approach to protecting public health.

PMID- 25947312
TI  - Long-term particulate matter exposure: Attributing health effects to individual
      PM components.
AB  - While most in the scientific community are of the opinion that the composition of
      fine particulate matter (PM2.5) is an important driver of resultant health
      effects, there is still some degree of uncertainty regarding those components
      considered to be most harmful. Reviews of the subject from several perspectives
      have been published, but to our knowledge a comprehensive review of the
      epidemiological and toxicological literature related to long-term exposure to
      PM2.5 components does not exist. We reviewed published epidemiological studies
      that were of a cohort design, included at least one PM component as well as PM2.5
      mass, and included quantitative analysis to relate health outcomes to individual
      components. Toxicological studies were included if they were >=5 months in
      duration and either included at least one PM component as well as PM mass or
      focused on a specific PM or emissions type. Overall, we find that epidemiological
      and toxicological evidence for long-term effects of PM components is limited, in
      contrast to the short-term literature, which is more plentiful. Epidemiological
      literature suggests that a number of components are associated with health
      effects, and that no component is unequivocally not so associated. Toxicological
      studies that can more easily identify potentially causal components are generally
      limited to long-term studies using concentrated ambient particles (CAPs), of
      which few long-term studies exist. Epidemiological study designs that utilize
      existing monitoring data routinely collected by the U.S. Environmental Protection
      Agency would be valuable additions to the literature, as would novel
      toxicological studies that incorporate innovative designs to separate components
      or groups of components, such as denuders, filtration, or other approaches. From
      a policy perspective, it is important to more comprehensively investigate this
      issue so that if particular constituents are determined to be more potent in
      inducing health effects, their sources can be controlled. IMPLICATIONS:
      Understanding the components of PM2.5 that are most harmful to human health is a
      critical policy issue. This review examined the epidemiological and toxicological
      literature related to long-term exposure to PM components and found that, unlike
      the literature on short-term health effects, there is insufficient information to
      make clear inferences about causal components. There is a need for further
      research in this area to exploit existing PM monitoring data in epidemiological
      studies and to design experimental studies that are able to tease out the effects
      of multiple constituents.

PMID- 25947314
TI  - Respiratory hospitalizations in association with fine PM and its components in
      New York State.
AB  - Despite observed geographic and temporal variation in particulate matter (PM)
      related health morbidities, only a small number of epidemiologic studies have
      evaluated the relation between PM2.5 chemical constituents and respiratory
      disease. Most assessments are limited by inadequate spatial and temporal
      resolution of ambient PM measurements and/or by their approaches to examine the
      role of specific PM components on health outcomes. In a case-crossover analysis
      using daily average ambient PM2.5 total mass and species estimates derived from
      the Community Multiscale Air Quality (CMAQ) model and available observations, we
      examined the association between the chemical components of PM (including
      elemental and organic carbon, sulfate, nitrate, ammonium, and other remaining)
      and respiratory hospitalizations in New York State. We evaluated relationships
      between levels (low, medium, high) of PM constituent mass fractions, and assessed
      modification of the PM2.5-hospitalization association via models stratified by
      mass fractions of both primary and secondary PM components. In our results,
      average daily PM2.5 concentrations in New York State were generally lower than
      the 24-hr average National Ambient Air Quality Standard (NAAQS). Year-round
      analyses showed statistically significant positive associations between
      respiratory hospitalizations and PM2.5 total mass, sulfate, nitrate, and ammonium
      concentrations at multiple exposure lags (0.5-2.0% per interquartile range [IQR]
      increase). Primarily in the summer months, the greatest associations with
      respiratory hospitalizations were observed per IQR increase in the secondary
      species sulfate and ammonium concentrations at lags of 1-4 days (1.0-2.0%).
      Although there were subtle differences in associations observed between mass
      fraction tertiles, there was no strong evidence to support modification of the
      PM2.5-respiratory disease association by a particular constituent. We conclude
      that ambient concentrations of PM2.5 and secondary aerosols including sulfate,
      ammonium, and nitrate were positively associated with respiratory
      hospitalizations, although patterns varied by season. Exposure to specific fine
      PM constituents is a plausible risk factor for respiratory hospitalization in New
      York State. IMPLICATIONS: The association between ambient concentrations of PM2.5
      components has been evaluated in only a small number of epidemiologic studies
      with refined spatial and temporal scale data. In New York State, fine PM and
      several of its constituents, including sulfate, ammonium, and nitrate, were
      positively associated with respiratory hospitalizations. Results suggest that PM
      species relationships and their influence on respiratory endpoints are complex
      and season dependent. Additional work is needed to better understand the relative
      toxicity of PM species, and to further explore the role of co-pollutant
      relationships and exposure prediction error on observed PM-respiratory disease
      associations.

PMID- 25947315
TI  - The geographic distribution and economic value of climate change-related ozone
      health impacts in the United States in 2030.
AB  - In this United States-focused analysis we use outputs from two general
      circulation models (GCMs) driven by different greenhouse gas forcing scenarios as
      inputs to regional climate and chemical transport models to investigate potential
      changes in near-term U.S. air quality due to climate change. We conduct multiyear
      simulations to account for interannual variability and characterize the near-term
      influence of a changing climate on tropospheric ozone-related health impacts near
      the year 2030, which is a policy-relevant time frame that is subject to fewer
      uncertainties than other approaches employed in the literature. We adopt a 2030
      emissions inventory that accounts for fully implementing anthropogenic emissions
      controls required by federal, state, and/or local policies, which is projected to
      strongly influence future ozone levels. We quantify a comprehensive suite of
      ozone-related mortality and morbidity impacts including emergency department
      visits, hospital admissions, acute respiratory symptoms, and lost school days,
      and estimate the economic value of these impacts. Both GCMs project average daily
      maximum temperature to increase by 1-4 degrees C and 1-5 ppb increases in daily 8
      hr maximum ozone at 2030, though each climate scenario produces ozone levels that
      vary greatly over space and time. We estimate tens to thousands of additional
      ozone-related premature deaths and illnesses per year for these two scenarios and
      calculate an economic burden of these health outcomes of hundreds of millions to
      tens of billions of U.S. dollars (2010$). IMPLICATIONS: Near-term changes to the
      climate have the potential to greatly affect ground-level ozone. Using a 2030
      emission inventory with regional climate fields downscaled from two general
      circulation models, we project mean temperature increases of 1 to 4 degrees C and
      climate-driven mean daily 8-hr maximum ozone increases of 1-5 ppb, though each
      climate scenario produces ozone levels that vary significantly over space and
      time. These increased ozone levels are estimated to result in tens to thousands
      of ozone-related premature deaths and illnesses per year and an economic burden
      of hundreds of millions to tens of billions of U.S. dollars (2010$).

PMID- 25947317
TI  - Impact of smoke from prescribed burning: Is it a public health concern?
AB  - Given the increase in wildfire intensity and frequency worldwide, prescribed
      burning is becoming a more common and widespread practice. Prescribed burning is
      a fire management tool used to reduce fuel loads for wildfire suppression
      purposes and occurs on an annual basis in many parts of the world. Smoke from
      prescribed burning can have a substantial impact on air quality and the
      environment. Prescribed burning is a significant source of fine particulate
      matter (PM2.5 aerodynamic diameter<2.5um) and these particulates are found to be
      consistently elevated during smoke events. Due to their fine nature PM2.5 are
      particularly harmful to human health. Here we discuss the impact of prescribed
      burning on air quality particularly focussing on PM2.5. We have summarised
      available case studies from Australia including a recent study we conducted in
      regional Victoria, Australia during the prescribed burning season in 2013. The
      studies reported very high short-term (hourly) concentrations of PM2.5 during
      prescribed burning. Given the increase in PM2.5 concentrations during smoke
      events, there is a need to understand the influence of prescribed burning smoke
      exposure on human health. This is important especially since adverse health
      impacts have been observed during wildfire events when PM2.5 concentrations were
      similar to those observed during prescribed burning events. Robust research is
      required to quantify and determine health impacts from prescribed burning smoke
      exposure and derive evidence based interventions for managing the risk.
      IMPLICATIONS: Given the increase in PM2.5 concentrations during PB smoke events
      and its impact on the local air quality, the need to understand the influence of
      PB smoke exposure on human health is important. This knowledge will be important
      to inform policy and practice of the integrated, consistent, and adaptive
      approach to the appropriate planning and implementation of public health
      strategies during PB events. This will also have important implications for land
      management and public health organizations in developing evidence based
      objectives to minimize the risk of PB smoke exposure.

PMID- 25947316
TI  - An assessment of air pollutant exposure methods in Mexico City, Mexico.
AB  - Geostatistical interpolation methods to estimate individual exposure to outdoor
      air pollutants can be used in pregnancy cohorts where personal exposure data are
      not collected. Our objectives were to a) develop four assessment methods
      (citywide average (CWA); nearest monitor (NM); inverse distance weighting (IDW);
      and ordinary Kriging (OK)), and b) compare daily metrics and cross-validations of
      interpolation models. We obtained 2008 hourly data from Mexico City's outdoor air
      monitoring network for PM10, PM2.5, O3, CO, NO2, and SO2 and constructed daily
      exposure metrics for 1,000 simulated individual locations across five populated
      geographic zones. Descriptive statistics from all methods were calculated for dry
      and wet seasons, and by zone. We also evaluated IDW and OK methods' ability to
      predict measured concentrations at monitors using cross validation and a
      coefficient of variation (COV). All methods were performed using SAS 9.3, except
      ordinary Kriging which was modeled using R's gstat package. Overall, mean
      concentrations and standard deviations were similar among the different methods
      for each pollutant. Correlations between methods were generally high (r=0.77 to
      0.99). However, ranges of estimated concentrations determined by NM, IDW, and OK
      were wider than the ranges for CWA. Root mean square errors for OK were
      consistently equal to or lower than for the IDW method. OK standard errors varied
      considerably between pollutants and the computed COVs ranged from 0.46 (least
      error) for SO2 and PM10 to 3.91 (most error) for PM2.5. OK predicted
      concentrations measured at the monitors better than IDW and NM. Given the
      similarity in results for the exposure methods, OK is preferred because this
      method alone provides predicted standard errors which can be incorporated in
      statistical models. The daily estimated exposures calculated using these
      different exposure methods provide flexibility to evaluate multiple windows of
      exposure during pregnancy, not just trimester or pregnancy-long exposures.
      IMPLICATIONS: Many studies evaluating associations between outdoor air pollution
      and adverse pregnancy outcomes rely on outdoor air pollution monitoring data
      linked to information gathered from large birth registries, and often lack
      residence location information needed to estimate individual exposure. This study
      simulated 1,000 residential locations to evaluate four air pollution exposure
      assessment methods, and describes possible exposure misclassification from using
      spatial averaging versus geostatistical interpolation models. An implication of
      this work is that policies to reduce air pollution and exposure among pregnant
      women based on epidemiologic literature should take into account possible error
      in estimates of effect when spatial averages alone are evaluated.

PMID- 25947318
TI  - The relationship between daily cardiovascular mortality and daily ambient
      concentrations of particulate pollutants (sulfur, arsenic, selenium, and mercury)
      and daily source contributions from coal power plants and smelters (individually,
      combined, and with interaction) in Phoenix, AZ, 1995-1998: A multipollutant
      approach to acute, time-series air pollution epidemiology: I.
AB  - The objective of this paper is to estimate the increase in risk of daily
      cardiovascular mortality due to an increase in the daily ambient concentration of
      the individual particulate pollutants sulfur (S), arsenic (As), selenium (Se),
      and mercury (Hg) using single-pollutant models (SPMs) and to compare this risk to
      the combined increase in risk due to an increase in all four pollutants by
      including all four pollutants in the same model (multipollutant model, MPM) and
      to the risks from source contributions from power plants and smelters. Individual
      betas in a multipollutant model (MPM) were summed to give a combined beta.
      Interaction was investigated with a pollutant product term. SPMs (controlling for
      time trends, temperature, and relative humidity), for an interquartile range
      (IQR) increase in the pollutant concentration on lag day 0, gave these percent
      excess risks (+/-95% confidence levels): S, 6.9% (1.3-12%); As, 2.9% (0.4-5.5%);
      Se, 1.4% (-1.7 to 4.6); Hg, 9.6% (4.8-14.6%). The SPM beta for S (as sulfate) was
      higher than found in other studies. The SPM beta for Hg gave the largest t
      statistic and beta per unit mass of any pollutant studied. An (IQR) increase in
      all four pollutants gave an excess risk of 15.4% (7.5-23.8%), slightly smaller
      than the combination of S and Hg, 16.7% (9.1-24.9%). The combined beta was 71% of
      the sum of the four individual SPM betas, indicating a reduction in confounding
      among pollutants in the combined model. As and Se were shown to be noncausal;
      their SPM betas could be explained as confounding by S. IMPLICATIONS: The
      combined effect of several pollutants can be estimated by including the
      appropriate pollutants in the same statistical model, summing their individual
      betas to give a combined beta, and using a variance-covariance matrix to obtain
      the standard error. This approach identifies and reduces confounding among the
      species in the multipollutant model and can be used to identify confounded
      species that have no independent relationship with mortality. The effect of
      several pollutants acting together may be higher than that of one pollutant.
      Further work is needed to understand the strong relationship of mortality with
      particulate mercury and sulfate.

PMID- 25947319
TI  - Estimation of future PM2.5- and ozone-related mortality over the continental
      United States in a changing climate: An application of high-resolution dynamical
      downscaling technique.
AB  - This paper evaluates the PM2.5- and ozone-related mortality at present (2000s)
      and in the future (2050s) over the continental United States by using the
      Environmental Benefits Mapping and Analysis Program (BenMAP-CE). Atmospheric
      chemical fields are simulated by WRF/CMAQ (horizontal resolution: 12*12 km),
      applying the dynamical downscaling technique from global climate-chemistry model
      under the Representative Concentration Pathways scenario (RCP 8.5). Future air
      quality results predict that the annual mean PM2.5 concentration in continental
      U.S. decreases nationwide, especially in the Eastern U.S. and west coast.
      However, the ozone concentration is projected to decrease in the Eastern U.S. but
      increase in the Western U.S. Future mortality is evaluated under two scenarios
      (1) holding future population and baseline incidence rate at the present level
      and (2) using the projected baseline incidence rate and population in 2050. For
      PM2.5, the entire continental U.S. presents a decreasing trend of PM2.5-related
      mortality by the 2050s in Scenario (1), primarily resulting from the emissions
      reduction. While in Scenario (2), almost half of the continental states show a
      rising tendency of PM2.5-related mortality, due to the dominant influence of
      population growth. In particular, the highest PM2.5-related deaths and the
      biggest discrepancy between present and future PM2.5-related deaths both occur in
      California in 2050s. For the ozone-related premature mortality, the simulation
      shows nation-wide rising tendency in 2050s under both scenarios, mainly due to
      the increase of ozone concentration and population in the future. Furthermore,
      the uncertainty analysis shows that the confidence interval of all causes
      mortality is much larger than that for specific causes, probably due to the
      accumulated uncertainty of generating datasets and sample size. The confidence
      interval of ozone-related all cause premature mortality is narrower than the
      PM2.5-related all cause mortality, due to its smaller standard deviation of the
      concentration-mortality response factor. IMPLICATIONS: The health impact of PM2.5
      is more linearly proportional to the emission reductions than ozone. The
      reduction of anthropogenic PM2.5 precursor emissions is likely to lead to the
      decrease of PM2.5 concentrations and PM2.5 related mortality. However, the future
      ozone concentrations could increase due to increase of the greenhouse gas
      emissions of methane. Thus, to reduce the impact of ozone related mortality,
      anthropogenic emissions including criteria pollutant and greenhouse gas (i.e.
      methane) need to be controlled.

PMID- 25947320
TI  - Secondhand smoke exposure is associated with smoke-free laws but not urban/rural
      status.
AB  - The objective was to determine secondhand smoke (SHS) exposure with and without
      smoke-free laws in urban and rural communities. The research hypothesis was that
      SHS exposure in public places could be improved by smoke-free law regardless of
      urban and rural status. Indoor air quality in hospitality venues was assessed in
      53 communities (16 urban and 37 rural) before smoke-free laws; 12 communities
      passed smoke-free laws during the study period. Real-time measurements of
      particulate matter with 2.5 um aerodynamic diameter or smaller (PM2.5) were taken
      657 times from 586 distinct venues; about 71 venues had both pre- and post-law
      measurements. Predictors of log-transformed PM2.5 level were determined using
      multilevel modeling. With covariates of county-level percent minority population,
      percent with at least high school education, adult smoking rate, and venue-level
      smoker density, indoor air quality was associated with smoke-free policy status
      and venue type and their interaction. The geometric means for restaurants, bars,
      and other public places in communities without smoke-free policies were 22, 63,
      and 25 times higher than in those with smoke-free laws, respectively. Indoor air
      quality was not associated with urban status of venue, and none of the
      interactions involving urban status were significant. SHS exposure in public
      places did not differ by urban/rural status. Indoor air quality was associated
      with smoke-free law status and venue type. IMPLICATIONS: This study analyzed 657
      measurements of indoor PM2.5 level in 53 communities in Kentucky, USA. Although
      indoor air quality in public places was associated with smoke-free policy status
      and venue type, it did not differ by urban and rural status. The finding supports
      the idea that population in rural communities can be protected with smoke-free
      policy. Therefore, it is critical to implement smoke-free policy in rural
      communities as well as urban areas.

PMID- 25947321
TI  - Exploring the modeling of spatiotemporal variations in ambient air pollution
      within the land use regression framework: Estimation of PM10 concentrations on a
      daily basis.
AB  - Estimation of daily average exposure to PM10 (particulate matter with an
      aerodynamic diameter<10 MUm) using the available fixed-site monitoring stations
      (FSMs) in a city poses a great challenge. This is because typically FSMs are
      limited in number when considering the spatial representativeness of their
      measurements and also because statistical models of citywide exposure have yet to
      be explored in this context. This paper deals with the later aspect of this
      challenge and extends the widely used land use regression (LUR) approach to deal
      with temporal changes in air pollution and the influence of transboundary air
      pollution on short-term variations in PM10. Using the concept of multiple linear
      regression (MLR) modeling, the average daily concentrations of PM10 in two
      European cities, Vienna and Dublin, were modeled. Models were initially developed
      using the standard MLR approach in Vienna using the most recently available data.
      Efforts were subsequently made to (i) assess the stability of model predictions
      over time; (ii) explores the applicability of nonparametric regression (NPR) and
      artificial neural networks (ANNs) to deal with the nonlinearity of input
      variables. The predictive performance of the MLR models of the both cities was
      demonstrated to be stable over time and to produce similar results. However, NPR
      and ANN were found to have more improvement in the predictive performance in both
      cities. Using ANN produced the highest result, with daily PM10 exposure predicted
      at R2=66% for Vienna and 51% for Dublin. In addition, two new predictor variables
      were also assessed for the Dublin model. The variables representing transboundary
      air pollution and peak traffic count were found to account for 6.5% and 12.7% of
      the variation in average daily PM10 concentration. The variable representing
      transboundary air pollution that was derived from air mass history (from back
      trajectory analysis) and population density has demonstrated a positive impact on
      model performance. IMPLICATIONS: The implications of this research would suggest
      that it is possible to produce a model of ambient air quality on a citywide scale
      using the readily available data. Most European cities typically have a limited
      FSM network with average daily concentrations of air pollutants as well as
      available meteorological, traffic, and land-use data. This research highlights
      that using these data in combination with advanced statistical techniques such as
      NPR or ANNs will produce reasonably accurate predictions of ambient air quality
      across a city, including temporal variations. Therefore, this approach reduces
      the need for additional measurement data to supplement existing historical
      records and enables a lower-cost method of air pollution model development for
      practitioners and policy makers.

PMID- 25947322
TI  - Dynamic changes in subcellular localization of cattle XLF during cell cycle, and
      focus formation of cattle XLF at DNA damage sites immediately after irradiation.
AB  - Clinically, many chemotherapeutics and ionizing radiation (IR) have been applied
      for the treatment of various types of human and animal malignancies. These
      treatments kill tumor cells by causing DNA double-strand breaks (DSBs). Core
      factors of classical nonhomologous DNA-end joining (C-NHEJ) play a vital role in
      DSB repair. Thus, it is indispensable to clarify the mechanisms of C-NHEJ in
      order to develop next-generation chemotherapeutics for cancer. The XRCC4-like
      factor (XLF; also called Cernunnos or NHEJ1) is the lastly identified core NHEJ
      factor. The localization of core NHEJ factors might play a critical role in
      regulating NHEJ activity. The localization and function of XLF have not been
      elucidated in animal species other than mice and humans. Domestic cattle (Bos
      taurus) are the most common and vital domestic animals in many countries. Here,
      we show that the localization of cattle XLF changes dynamically during the cell
      cycle. Furthermore, EYFP-cattle XLF accumulates quickly at microirradiated sites
      and colocalizes with the DSB marker gammaH2AX. Moreover, nuclear localization and
      accumulation of cattle XLF at DSB sites are dependent on 12 amino acids (288-299)
      of the C-terminal region of XLF (XLF CTR). Furthermore, basic amino acids on the
      XLF CTR are highly conserved among domestic animals including cattle, goat and
      horses, suggesting that the CTR is essential for the function of XLF in domestic
      animals. These findings might be useful to develop the molecular-targeting
      therapeutic drug taking XLF as a target molecule for human and domestic animals.

PMID- 25947323
TI  - Nuclear localization of mouse Ku70 in interphase cells and focus formation of
      mouse Ku70 at DNA damage sites immediately after irradiation.
AB  - To elucidate the mechanisms of DNA repair pathway is critical for developing next
      generation radiotherapies and chemotherapeutic drugs for cancer. Ionizing
      radiation and many chemotherapeutic drugs kill tumor cells mainly by inducing DNA
      double-strand breaks (DSBs). The classical nonhomologous DNA-end joining (NHEJ)
      (C-NHEJ) pathway repairs a predominant fraction of DSBs in mammalian cells. The C
      NHEJ pathway appears to start with the binding of Ku (heterodimer of Ku70 and
      Ku80) to DNA break ends. Therefore, recruitment of Ku to DSB sites might play a
      critical role in regulating NHEJ activity. Indeed, human Ku70 and Ku80 localize
      in the nuclei and accumulate at microirradiated DSB sites. However, the
      localization and regulation mechanisms of Ku70 and Ku80 homologues in animal
      models, such as mice and other species, have not been elucidated in detail,
      particularly in cells immediately after microirradiation. Here, we show that EYFP
      tagged mouse Ku70 localizes in the interphase nuclei of mouse fibroblasts and
      epithelial cells. Furthermore, our findings indicate that EYFP-mouse Ku70
      accumulates with its heterodimeric partner Ku80 immediately at laser
      microirradiated DSB sites. We also confirmed that the structure of Ku70 nuclear
      localization signal (NLS) is highly conserved among various rodent species, such
      as the mouse, rat, degu and ground squirrel, supporting the idea that NLS is
      important for the regulation of rodent Ku70 function. Collectively, these results
      suggest that the mechanisms of regulating the localization and accumulation of
      Ku70 at DSBs might be well conserved between the mouse and human species.

PMID- 25947324
TI  - Effect of cyclosporin on distribution of methotrexate into the brain of rats.
AB  - The effect of the antitumor drug, methotrexate (MTX), which is applied to brain
      tumors, is restricted by the blood-brain barrier (BBB), which is composed of P
      glycoprotein (P-gp) and multidrug resistance associated protein (MRP). We,
      therefore, studied if a potent P-gp and MRP modulator, cyclosporin A (CysA), can
      modulate the MTX concentration in the rat brain. If it can, which route is more
      effective, intravenous or intrathecal? We intravenously or intrathecally
      administered MTX to rats with or without CysA. After 6 hr, brains and
      cerebrospinal fluid (CSF) were sampled, and their MTX concentrations were
      compared. Each MTX concentration was determined by high-performance liquid
      chromatography with UV detection. CysA had no significant affect on the MTX
      concentration in the brain or CSF when MTX was intravenously injected. In
      contrast, when MTX was intrathecally administered, CysA had a larger effect on
      the MTX concentration in the brain than in the CSF. This indicates CysA
      potentiated the brain MTX concentration when MTX was intrathecally administered.
      It is suggested that CysA did not potentiate the distribution of MTX from blood
      into the brain, but instead potentiated the distribution of MTX from CSF into the
      brain. Since chemicals in CSF generally diffuse into the brain easily, CysA
      probably inhibited the excretion of MTX from the brain. This could be caused by
      inhibition of P-gp or MRP at the BBB. Therefore, CysA can be a useful tool to
      achieve an appropriate MTX concentration in brain.

PMID- 25947326
TI  - Short answer question: a distracting ECG.

PMID- 25947325
TI  - Physical activity and the association with fatigue and sleep in Danish patients
      with rheumatoid arthritis.
AB  - The aim of this study was to examine physical activity behavior in patients with
      rheumatoid arthritis and to identify potential correlates of regular physical
      activity including fatigue, sleep, pain, physical function and disease activity.
      A total of 443 patients were recruited from a rheumatology outpatient clinic and
      included in this cross-sectional study. Physical activity was assessed by a four
      class questionnaire, in addition to the Physical Activity Scale. Other
      instruments included the Multidimensional Fatigue Inventory (MFI), the Pittsburgh
      Sleep Quality Index and the Health Assessment Questionnaire. Disease activity was
      obtained from a nationwide clinical database. Of the included patients, 80 % were
      female and mean age was 60 (range 21-88 years). Hereof, 22 % (n = 96) were
      regularly physically active, and 78 % (n = 349) were mainly sedentary or having a
      low level of physical activity. An inverse univariate association was found
      between moderate to vigorous physical activity, and fatigue (MFI mental, MFI
      activity, MFI physical and MFI general), sleep, diabetes, depression, pain,
      patient global assessment, HAQ and disease activity. The multivariate prediction
      model demonstrated that fatigue-related reduced activity and physical fatigue
      were selected in >95 % of the bootstrap samples with median odds ratio 0.89 (2.5
      97.5 % quantiles: 0.78-1.00) and 0.91 (2.5-97.5 % quantiles: 0.81-0.97),
      respectively, while disease activity was selected in 82 % of the bootstrap
      samples with median odds ratio 0.90. Moderate to vigorous physical activity in
      patients with rheumatoid arthritis is associated with the absence of several RA
      related factors with the most important correlates being reduced activity due to
      fatigue, physical fatigue and disease activity. 

PMID- 25947327
TI  - A comprehensive method to develop a checklist to increase safety of intra
      hospital transport of critically ill patients.
AB  - INTRODUCTION: Transport of critically ill patients from the Intensive Care Unit
      (ICU) to other departments for diagnostic or therapeutic procedures is often a
      necessary part of the critical care process. Transport of critically ill patients
      is potentially dangerous with up to 70% adverse events occurring. The aim of this
      study was to develop a checklist to increase safety of intra-hospital transport
      (IHT) in critically ill patients. METHOD: A three-step approach was used to
      develop an IHT checklist. First, various databases were searched for published
      IHT guidelines and checklists. Secondly, prospectively collected IHT incidents in
      the LUMC ICU were analyzed. Thirdly, interviews were held with physicians and
      nurses over their experiences of IHT incidents. Following this approach a
      checklist was developed and discussed with experts in the field. Finally,
      feasibility and usability of the checklist was tested. RESULTS: Eleven existing
      guidelines and five checklists were found. Only one checklist covered all three
      phases: pre-, during- and post-transport. Recommendations and checklist items
      mostly focused on the pre-transport phase. Documented incidents most frequently
      related to patient physiology and equipment malfunction and occurred most often
      during transport. Discussing the incidents with ICU physicians and ICU nurses
      resulted in important recommendations such as the introduction of a standard
      checklist and improved communication with the other departments. This approach
      resulted in a generally applicable checklist, adaptable for local circumstances.
      Feedback from nurses using the checklist were positive, the fill in time was 4.5
      minutes per phase. CONCLUSION: A comprehensive way to develop an intra-hospital
      checklist for safe transport of ICU patients to another department is described.
      This resulted in a checklist which is a framework to guide physicians and nurses
      through intra-hospital transports and provides a continuity of care to enhance
      patient safety. Other hospitals can customize this checklist to their own
      situation using the methods proposed in this paper.

PMID- 25947330
TI  - Characterising 'near miss' events in complex laparoscopic surgery through video
      analysis.
AB  - BACKGROUND: Root cause analyses of surgical complications are of high importance
      to ensure surgical quality, but specific details on technical causes often remain
      unclear. Identifying subclinical intraoperative incidents attributable to
      technical errors is essential for developing rescue mechanisms to prevent adverse
      outcomes. OBJECTIVE: Descriptive study to characterise intraoperative technical
      error-event patterns in successful laparoscopic procedures. METHODS: Events
      (injuries) identified during prior blinded analyses of 54 unedited recordings of
      bariatric laparoscopic procedures were subjected to a secondary review to
      determine the presumed underlying error mechanism. The recordings were obtained
      from one university-based bariatric collaborative programme, and represented
      consultant, fellow and shared trainee cases. RESULTS: Sixty-six events were
      identified in 38 recordings, while 16 videos showed no events. In 25 (66%) of the
      videos that showed events, additional measures such as haemostasis or suture
      repair were required. Common identified events were minor bleeding (n=39, 59%),
      thermal injury to non-target tissue (n=7, 11%), serosal tears (n=6, 9%). Common
      error mechanisms were 'inadequate use of force/distance (too much)' (n=20, 30%)
      and 'inadequate visualisation' during grasping/dissecting (n=6, 9%), 'inadequate
      use of force/distance (too much)' using an energy device (n=6, 9%), or during
      suturing (n=6, 9%). All events were recognised intraoperatively. CONCLUSIONS:
      Analysis of successful operations allowed the identification of numerous error
      event sequences. Reviewing injury mechanisms can enhance surgeons' understanding
      of relevant errors. This error awareness may aid surgeons in preparing for cases,
      help avoid errors and mitigate their consequences. Thus, this approach may impact
      future surgical education and quality initiatives aimed at reducing surgical
      risks.

PMID- 25947329
TI  - ALIFE2 study: low-molecular-weight heparin for women with recurrent miscarriage
      and inherited thrombophilia--study protocol for a randomized controlled trial.
AB  - BACKGROUND: A large number of studies have shown an association between inherited
      thrombophilia and recurrent miscarriage. It has been hypothesized that
      anticoagulant therapy might reduce the number of miscarriages and stillbirth in
      these women. In the absence of randomized controlled trials evaluating the
      efficacy of anticoagulant therapy in women with inherited thrombophilia and
      recurrent miscarriage, a randomized trial with adequate power that addresses this
      question is needed. The objective of the ALIFE2 study is therefore to evaluate
      the efficacy of low-molecular-weight heparin (LMWH) in women with inherited
      thrombophilia and recurrent miscarriage, with live birth as the primary outcome.
      METHODS/DESIGN: Randomized study of LMWH plus standard pregnancy surveillance
      versus standard pregnancy surveillance alone. STUDY POPULATION: pregnant women of
      less than 7 weeks' gestation, and confirmed inherited thrombophilia with a
      history of 2 or more miscarriages or intra-uterine fetal deaths, or both.
      SETTING: multi-center study in centers from the Dutch Consortium of Fertility
      studies; centers outside the Netherlands are currently preparing to participate.
      INTERVENTION: LMWH enoxaparin 40 mg subcutaneously once daily started prior to 7
      weeks gestational age plus standard pregnancy surveillance or standard pregnancy
      surveillance alone. Main study parameters/endpoints: the primary efficacy outcome
      is live birth. Secondary efficacy outcomes include adverse pregnancy outcomes,
      such as miscarriage, pre-eclampsia, syndrome of hemolysis, elevated liver enzymes
      and low platelets (HELLP syndrome), fetal growth restriction, placental
      abruption, premature delivery and congenital malformations. Safety outcomes
      include bleeding episodes, thrombocytopenia and skin reactions. DISCUSSION: After
      an initial period of slow recruitment, the recruitment rate for the study has
      increased. Improved awareness of the study and acknowledgement of the need for
      evidence are thought to be contributing to the improved recruitment rates. We aim
      to increase the number of recruiting centers in order to increase enrollment into
      the ALIFE2 study. The study website can be accessed via www.ALIFE2study.org.
      TRIAL REGISTRATION: The ALIFE2 study was registered on 19 March 2012 under
      registration number NTR3361.

PMID- 25947328
TI  - Dysbiotic drift: mental health, environmental grey space, and microbiota.
AB  - Advances in research concerning the mental health implications of dietary
      patterns and select nutrients have been remarkable. At the same time, there have
      been rapid increases in the understanding of the ways in which non-pathogenic
      microbes can potentially influence many aspects of human health, including those
      in the mental realm. Discussions of nutrition and microbiota are often
      overlapping. A separate, yet equally connected, avenue of research is that
      related to natural (for example, green space) and built environments, and in
      particular, how they are connected to human cognition and behaviors. It is argued
      here that in Western industrial nations a 'disparity of microbiota' might be
      expected among the socioeconomically disadvantaged, those whom face more profound
      environmental forces. Many of the environmental forces pushing against the
      vulnerable are at the neighborhood level. Matching the developing microbiome
      research with existing environmental justice research suggests that grey space
      may promote dysbiosis by default. In addition, the influence of Westernized
      lifestyle patterns, and the marketing forces that drive unhealthy behaviors in
      deprived communities, might allow dysbiosis to be the norm rather than the
      exception in those already at high risk of depression, subthreshold
      (subsyndromal) conditions, and subpar mental health. If microbiota are indeed at
      the intersection of nutrition, environmental health, and lifestyle medicine (as
      these avenues pertain to mental health), then perhaps the rapidly evolving gut
      brain-microbiota conversation needs to operate through a wider lens. In contrast
      to the more narrowly defined psychobiotic, the term eco-psychotropic is
      introduced. 

PMID- 25947332
TI  - Post-polypectomy Guideline Adherence: Importance of Belief in Guidelines, Not
      Guideline Knowledge or Fear of Missed Cancer.
AB  - BACKGROUND: Adherence to post-polypectomy surveillance guideline recommendations
      is suboptimal. Surveillance is frequently over- and under-recommend, resulting in
      strained colonoscopy capacity, potential risks without expected benefits, and
      missed opportunities for colorectal cancer risk reduction. AIMS: To identify
      factors associated with adherence to post-polypectomy surveillance guidelines.
      METHODS: We conducted a three-phase study with a retrospective review of usual
      care post-polypectomy surveillance recommendations through medical chart
      abstraction (Phase I), prospective online physician survey (Phase II), and
      analysis of survey-based and other physician-based predictors of usual care
      surveillance recommendations (Phase III). Subjects included patients who
      underwent usual care colonoscopy 2011-2012 (Phases I and III) and
      gastroenterology (GI) attendings and fellows (Phases II and III). We identified
      rates of recommendations consistent with guideline adherence, surveillance
      overuse, and surveillance underuse based on usual care medical chart
      documentation and physician survey, as well as predictors of physician adherence
      to guidelines. RESULTS: We reviewed 640 patient charts for 28 survey respondents.
      Rates of usual practice recommendations consistent with guideline adherence,
      surveillance overutilization, and underutilization were 84, 13, and 3%,
      respectively. At survey, 82% of physicians were concerned about missed cancer.
      Eleven percentage believed that guidelines were not aggressive enough. GI
      trainees were 2.5 times more likely to issue guideline-adherent recommendations
      [OR 2.5, 95% CI (1.5-4.2)]. Disagreement with guideline aggressiveness was
      independently associated with 40% lower likelihood of adherence [OR 0.6, 95% CI
      (0.4-0.8)]. CONCLUSIONS: Belief in the appropriate aggressiveness of guidelines
      and trainee position, but not fear of missed cancer or guideline knowledge, was
      associated with adherence to post-polypectomy surveillance guidelines.

PMID- 25947333
TI  - Glomerular hyperfiltration in hypogonadotropic hypogonadic patients: Overlooking
      a cache?
AB  - PURPOSE: To investigate renal function in idiopathic hypogonadotropic hypogonadic
      (IHH) patients by measuring glomerular filtration rate (GFR) using modification
      of diet in renal disease formula, and determine whether there is any relationship
      between GFR and testosterone levels. METHODS: Thirty-three patients with IHH and
      37 healthy control subjects participated in this study. RESULTS: The IHH group
      showed statistically significant higher GFR and proteinuria with respect to the
      control group (163.1 +/- 46.9 to 117.9 +/- 30.5 mL/min, p < 0.001; 0.2 +/- 0.1 to
      0.08 +/- 0.02 mg/dL, p = 0.041, respectively). Uric acid and creatinine levels
      were statistically lower than in the control group (4.6 +/- 0.5-3.6 +/- 0.9
      mg/dL, p = 0.02; 0.7 +/- 0.2 to 0.9 +/- 0.2 mg/dL, p < 0.001, respectively).
      Hyperfiltration positively correlated with IHH in multivariate linear regression
      analyses (beta = 0.591, p < 0.001). In addition, in the IHH group, we found that
      the GFR increased independently of body mass index and age. CONCLUSION: Our study
      confirms that low testosterone in IHH patients is associated with glomerular
      hyperfiltration. Patients with IHH should be carefully monitored with respect to
      their GFR.

PMID- 25947334
TI  - Staging studies for evaluation of squamous cell carcinoma. Staging of left
      temporal squamous cell carcinoma with PET-CT.

PMID- 25947331
TI  - Pregnancy and the Immune System: General Overview and the Gastroenterological
      Perspective.
AB  - Pregnancy represents a unique immune tolerant condition that cannot be attributed
      merely to generalized immunosuppression. A variety of mechanisms have been
      described, ranging from the non-self recognition, immunomodulation of specific
      inflammatory cell populations and a Th2-directed shift of the immune response,
      which are mediated by both localized and systemic mediators. Furthermore, an
      inflammatory response directed toward the conceptus is no longer considered an
      obligatory deleterious response; instead, it is considered an important factor
      that is necessary for normal growth and development. These immunomodulatory
      changes during pregnancy may also affect concurrent conditions and alter the
      course of inflammatory diseases. Herein, we review the main immunomodulatory
      changes that occur during pregnancy and their effect on coexisting inflammatory
      conditions, with a specific focus on gastrointestinal disorders. 

PMID- 25947336
TI  - Metal-organic framework biosensor with high stability and selectivity in a bio
      mimic environment.
AB  - A water-stable copper metal-organic framework (MOF), {[Cu2(HL)2(MU2
      OH)2(H2O)5].H2O}n (1, H2L = 2,5-dicarboxylic acid-3,4-ethylene dioxythiophene),
      was applied for the electrochemical detection of ascorbic acid (AA) without
      further post-modification. A glass carbon electrode covered with 1 was used as a
      biosensor for the simultaneous detection of AA and L-tryptophan (L-Trp) from both
      a single-component solution and a bio-mimic environment.

PMID- 25947337
TI  - The Secretome of Hydrogel-Coembedded Endothelial Progenitor Cells and Mesenchymal
      Stem Cells Instructs Macrophage Polarization in Endotoxemia.
AB  - : We previously reported the delivery of endothelial progenitor cells (EPCs)
      embedded in hyaluronic acid-based (HA)-hydrogels protects renal function during
      acute kidney injury (AKI) and promotes angiogenesis. We attempted to further
      ameliorate renal dysfunction by coembedding EPCs with renal mesenchymal stem
      cells (MSCs), while examining their paracrine influence on cytokine/chemokine
      release and proinflammatory macrophages. A live/dead assay determined whether EPC
      MSC coculturing improved viability during lipopolysaccharide (LPS) treatment, and
      HA-hydrogel-embedded delivery of cells to LPS-induced AKI mice was assessed for
      effects on mean arterial pressure (MAP), renal blood flow (RBF), circulating
      cytokines/chemokines, serum creatinine, proteinuria, and angiogenesis (femoral
      ligation). Cytokine/chemokine release from embedded stem cells was examined,
      including effects on macrophage polarization and release of proinflammatory
      molecules. EPC-MSC coculturing improved stem cell viability during LPS exposure,
      an effect augmented by MSC hypoxic preconditioning. The delivery of coembedded
      EPCs with hypoxic preconditioned MSCs to AKI mice demonstrated additive
      improvement (compared with EPC delivery alone) in medullary RBF and proteinuria,
      with comparable effects on serum creatinine, MAP, and angiogenesis. Exposure of
      proinflammatory M1 macrophages to EPC-MSC conditioned medium changed their
      polarization to anti-inflammatory M2. Incubation of coembedded EPCs-MSCs with
      macrophages altered their release of cytokines/chemokines, including enhanced
      release of anti-inflammatory interleukin (IL)-4 and IL-10. EPC-MSC delivery to
      endotoxemic mice elevated the levels of circulating M2 macrophages and reduced
      the circulating cytokines/chemokines. In conclusion, coembedding EPCs-MSCs
      improved their resistance to stress, impelled macrophage polarization from M1 to
      M2 while altering their cytokine/chemokines release, reduced circulating
      cytokines/chemokines, and improved renal and vascular function when MSCs were
      hypoxically preconditioned. SIGNIFICANCE: This report provides insight into a new
      therapeutic approach for treatment of sepsis and provides a new and improved
      strategy using hydrogels for the delivery of stem cells to treat sepsis and,
      potentially, other injuries and/or diseases. The delivery of two different stem
      cell lines (endothelial progenitor cells and mesenchymal stem cells; delivered
      alone and together) embedded in a protective bioengineered scaffolding (hydrogel)
      offers many therapeutic benefits for the treatment of sepsis. This study shows
      how hydrogel-delivered stem cells elicit their effects and how hydrogel embedding
      enhances the therapeutic efficacy of delivered stem cells. Hydrogel-delivered
      stem cells influence the components of the overactive immune system during sepsis
      and work to counterbalance the release of many proinflammatory and prodamage
      substances from immune cells, thereby improving the associated vascular and
      kidney damage.

PMID- 25947339
TI  - Mesenchymal-endothelial transition in juvenile angiofibroma?
AB  - CONCLUSION: Mesenchymal-endothelial transition is proposed for juvenile
      angiofibromas (JAs). Propranolol might be an interesting new medical option in JA
      treatment, as it reduces mesenchymal cell growth and decreases the number of CD31
      positive cells in vitro. OBJECTIVE: Juvenile angiofibromas (JAs) are rare fibro
      vascular tumors affecting almost exclusively adolescent males. Based on
      morphological aspects of irregularly configured vascular spaces and clinical
      features, JAs have been proposed to represent a vascular malformation. In
      general, mesenchymal-endothelial transition has been noted as an important
      process in tumorigenesis as well as in embryonal development. METHODS: The study
      analyzed effects of vascular endothelial growth factor (VEGF)/basic fibroblast
      growth factor (bFGF) and propranolol on endothelial differentiation (CD31+) of
      cultured JA cells and their expression of angiogenic growth factors using aortic
      ring assay and enzyme-linked immunosorbent assay. RESULTS: Following VEGF/bFGF
      supplement to cultured mesenchymal cells, an average of 4.47% (+/- 2.35%) CD31
      positive cells were found (p < 0.001). Propranolol addition reduced the number of
      CD31-positive cells and inhibited mesenchymal cell growth. The aortic ring assay
      and ELISA investigation indicated no increased angiogenic growth factor secretion
      from cultured JA mesenchymal cells.

PMID- 25947340
TI  - Synthesis of an unexpected [Zn2](2+) species utilizing an MFI-type zeolite as a
      nano-reaction pot and its manipulation with light and heat.
AB  - Compared with mercury, the existence of [Zn2](2+) species is rare. We succeeded
      in preparing a stable [Zn2](2+) species by utilizing an MFI-type zeolite as a
      nano-reaction pot, which was confirmed using XAFS spectroscopy: the bands at R =
      2.35 A due to the Zn(+)-Zn(+) scattering and at 9660.7 eV due to the 1s-sigma*
      (the anti-bonding orbital comprised of the 4s-4s orbital) transition of the
      [Zn2](2+) species. This species also gives the characteristic band around 42 000
      cm(-1) due to its sigma-sigma* transition. Furthermore, UV-irradiation
      corresponding to the sigma-sigma* transition causes the bond dissociation,
      forming two unprecedented Zn(+) ions, and detached Zn(+) ions were recombined
      through heat-treatment at 573 K: [Zn(+)-Zn(+)] ? 2Zn(+). These processes were
      reproduced by applying the DFT calculation method to the assumed triplet,
      sigma(alpha)-sigma*(alpha), structure formed on the M7-S2 site with the specific
      Al array in the MFI-type zeolite. Research into the specific field using zeolites
      to synthesize "ultra-state ions" is very promising. 

PMID- 25947338
TI  - Immunobiology of fibrin-based engineered heart tissue.
AB  - Different tissue-engineering approaches have been developed to induce and promote
      cardiac regeneration; however, the impact of the immune system and its responses
      to the various scaffold components of the engineered grafts remains unclear.
      Fibrin-based engineered heart tissue (EHT) was generated from neonatal Lewis
      (Lew) rat heart cells and transplanted onto the left ventricular surface of three
      different rat strains: syngeneic Lew, allogeneic Brown Norway, and
      immunodeficient Rowett Nude rats. Interferon spot frequency assay results showed
      similar degrees of systemic immune activation in the syngeneic and allogeneic
      groups, whereas no systemic immune response was detectable in the immunodeficient
      group (p < .001 vs. syngeneic and allogeneic). Histological analysis revealed
      much higher local infiltration of CD3- and CD68-positive cells in syngeneic and
      allogeneic rats than in immunodeficient animals. Enzyme-linked immunospot and
      immunofluorescence experiments revealed matrix-directed TH1-based rejection in
      syngeneic recipients without collateral impairment of heart cell survival.
      Bioluminescence imaging was used for in vivo longitudinal monitoring of
      transplanted luciferase-positive EHT constructs. Survival was documented in
      syngeneic and immunodeficient recipients for a period of up to 110 days after
      transplant, whereas in the allogeneic setting, graft survival was limited to only
      14 +/- 1 days. EHT strategies using autologous cells are promising approaches for
      cardiac repair applications. Although fibrin-based scaffold components elicited
      an immune response in our studies, syngeneic cells carried in the EHT were
      relatively unaffected. SIGNIFICANCE: An initial insight into immunological
      consequences after transplantation of engineered heart tissue was gained through
      this study. Most important, this study was able to demonstrate cell survival
      despite rejection of matrix components. Generation of syngeneic human engineered
      heart tissue, possibly using human induced pluripotent stem cell technology with
      subsequent directed rejection of matrix components, may be a potential future
      approach to replace diseased myocardium.

PMID- 25947341
TI  - Convergent evolution of cysteine-rich proteins in feathers and hair.
AB  - BACKGROUND: Feathers and hair consist of cornified epidermal keratinocytes in
      which proteins are crosslinked via disulfide bonds between cysteine residues of
      structural proteins to establish mechanical resilience. Cysteine-rich keratin
      associated proteins (KRTAPs) are important components of hair whereas the
      molecular components of feathers have remained incompletely known. Recently, we
      have identified a chicken gene, named epidermal differentiation cysteine-rich
      protein (EDCRP), that encodes a protein with a cysteine content of 36%. Here we
      have investigated the putative role of EDCRP in the molecular architecture and
      evolution of feathers. RESULTS: Comparative genomics showed that the presence of
      an EDCRP gene and the high cysteine content of the encoded proteins are conserved
      among birds. Avian EDCRPs contain a species-specific number of sequence repeats
      with the consensus sequence CCDPCQ(K/Q)(S/P)V, thus resembling mammalian cysteine
      rich KRTAPs which also contain sequence repeats of similar sequence. However,
      differences in gene loci and exon-intron structures suggest that EDCRP and KRTAPs
      have not evolved from a common gene ancestor but represent the products of
      convergent sequence evolution. mRNA in situ hybridization demonstrated that
      chicken EDCRP is expressed in the subperiderm layer of the embryonic epidermis
      and in the barbule cells of growing feathers. This expression pattern supports
      the hypothesis that feathers are evolutionarily derived from the subperiderm.
      CONCLUSIONS: The results of this study suggest that convergent sequence evolution
      of avian EDCRP and mammalian KRTAPs has contributed to independent evolution of
      feathers and hair, respectively.

PMID- 25947343
TI  - Magnesium protects against cisplatin-induced acute kidney injury without
      compromising cisplatin-mediated killing of an ovarian tumor xenograft in mice.
AB  - Cisplatin, a commonly used chemotherapeutic for ovarian and other cancers, leads
      to hypomagnesemia in most patients and causes acute kidney injury (AKI) in 25-30%
      of patients. Previously, we showed that magnesium deficiency worsens cisplatin
      induced AKI and magnesium replacement during cisplatin treatment protects against
      cisplatin-mediated AKI in non-tumor-bearing mice (Solanki MH, Chatterjee PK,
      Gupta M, Xue X, Plagov A, Metz MH, Mintz R, Singhal PC, Metz CN. Am J Physiol
      Renal Physiol 307: F369-F384, 2014). This study investigates the role of
      magnesium in cisplatin-induced AKI using a human ovarian tumor (A2780) xenograft
      model in mice and the effect of magnesium status on tumor growth and the
      chemotherapeutic efficacy of cisplatin in vivo. Tumor progression was unaffected
      by magnesium status in saline-treated mice. Cisplatin treatment reduced tumor
      growth in all mice, irrespective of magnesium status. In fact, cisplatin-treated
      magnesium-supplemented mice had reduced tumor growth after 3 wk compared with
      cisplatin-treated controls. While magnesium status did not interfere with tumor
      killing by cisplatin, it significantly affected renal function following
      cisplatin. Cisplatin-induced AKI was enhanced by magnesium deficiency, as
      evidenced by increased blood urea nitrogen, creatinine, and other markers of
      renal damage. This was accompanied by reduced renal mRNA expression of the
      cisplatin efflux transporter Abcc6. These effects were significantly reversed by
      magnesium replacement. On the contrary, magnesium status did not affect the mRNA
      expression of cisplatin uptake or efflux transporters by the tumors in vivo.
      Finally, magnesium deficiency enhanced platinum accumulation in the kidneys and
      renal epithelial cells, but not in the A2780 tumor cells. These findings
      demonstrate the renoprotective role of magnesium during cisplatin AKI, without
      compromising the chemotherapeutic efficacy of cisplatin in an ovarian tumor
      bearing mouse model. 

PMID- 25947342
TI  - NMDAR-Mediated Hippocampal Neuronal Death is Exacerbated by Activities of ASIC1a.
AB  - NMDARs and ASIC1a both exist in central synapses and mediate important
      physiological and pathological conditions, but the functional relationship
      between them is unclear. Here we report several novel findings that may shed
      light on the functional relationship between these two ion channels in the
      excitatory postsynaptic membrane of mouse hippocampus. Firstly, NMDAR activation
      induced by either NMDA or OGD led to increased [Ca(2+)](i)and greater apoptotic
      and necrotic cell deaths in cultured hippocampal neurons; these cell deaths were
      prevented by application of NMDAR antagonists. Secondly, ASIC1a activation
      induced by pH 6.0 extracellular solution (ECS) showed similar increases in
      apoptotic and necrotic cell deaths; these cell deaths were prevented by ASIC1a
      antagonists, and also by NMDAR antagonists. Since increased [Ca(2+)](i)leads to
      increased cell deaths and since NMDAR exhibits much greater calcium permeability
      than ASIC1a, these data suggest that ASIC1a-induced neuronal death is mediated
      through activation of NMDARs. Thirdly, treatment of hippocampal cultures with
      both NMDA and acidic ECS induced greater degrees of cell deaths than either NMDA
      or acidic ECS treatment alone. These results suggest that ASIC1a activation up
      regulates NMDAR function. Additional data supporting the functional relationship
      between ASIC1a and NMDAR are found in our electrophysiology experiments in
      hippocampal slices, where stimulation of ASIC1a induced a marked increase in
      NMDAR EPSC amplitude, and inhibition of ASIC1a resulted in a decrease in NMDAR
      EPSC amplitude. In summary, we present evidence that ASIC1a activity facilitates
      NMDAR function and exacerbates NMDAR-mediated neuronal death in pathological
      conditions. These findings are invaluable to the search for novel therapeutic
      targets in the treatment of brain ischemia.

PMID- 25947344
TI  - One physiology does not fit all: a path from data variability to
      "physiogenetics"?
AB  - Data variability is a costly complication of biomedical experimentation because
      the same experiment must be repeated a sufficient number of times so that the
      sample mean becomes a credible representation of the entire population. Since
      sampling is ideally done randomly in populations normalized for environmental and
      genetic backgrounds, data variability is viewed as a purely statistical issue
      reflecting the distribution in the population and captured as the standard
      deviation of the sampled data. The factors contributing to data variability are
      not analyzed by statistical methods; for want of a better explanation, data
      scatter is simply attributed to random noise and/or methodological limitations.
      In this commentary, evidence is discussed that documents an important role of
      interindividual biological diversity as a cause for data variability based on
      studies in which repeated sampling in the same individual permitted statistical
      comparisons between individuals in the same sample. Significant differences were
      found for proximal fluid reabsorption and plasma renin concentration between
      sample means of individuals of the same population. Furthermore, arterial blood
      pressure varied significantly between individual mice independently of strain and
      sex. Recognition of the extent of interindividual variability has important
      implications for data reproducibility, data collection, and data presentation in
      physiological research. Such nonrandom data variability may have different
      causes, but DNA modifications by genetic or epigenetic mechanisms could generate
      phenotype variants without being associated with disease symptoms. Exploration of
      the heritability of phenotypical diversity in physiology may be defined as
      "physiogenetics," and it would thus be the physiological corollary of
      pharmacogenetics and pharmacogenomics. 

PMID- 25947345
TI  - Sociological inquiry into mental health: the legacy of Leonard I. Pearlin.
AB  - As a tribute to the body of work created by our late colleague Leonard I.
      Pearlin, this essay assesses how the evolution of the Stress Process Model, the
      centerpiece of his work, repeatedly reinvented sociological research on stress
      and mental health and explains why this model, therefore, possesses the potential
      to renew itself well into the future. This essay revisits some of Pearlin's
      seminal contributions: the original specification of the stress process and three
      extensions of it--the concept of stress proliferation, the formulation of the
      role of social structure and functioning in the stress process, and the
      articulation of linkages between the stress process and the life course
      perspective. The resultant body of work has had formative influences on the ways
      sociologists now think about the impact of society on the inner emotional lives
      of its members.

PMID- 25947347
TI  - Spatiotemporal dynamics of excitons in monolayer and bulk WS2.
AB  - Spatiotemporal dynamics of excitons in monolayer and bulk WS2 at room temperature
      is studied by transient absorption microscopy in the reflection geometry.
      Excitons are formed from photocarriers injected by a tightly focused 390 nm pump
      pulse, and monitored by detecting different reflection of a time-delayed and
      spatially scanned 620 nm probe pulse. We obtain exciton lifetimes of 22 +/- 1 and
      110 +/- 10 ps in monolayer and bulk WS2, respectively. Both lifetimes are
      independent of the exciton density, showing the absence of multi-exciton
      recombination processes. Exciton diffusion coefficients of 60 +/- 20 and 3.5 +/-
      0.5 cm(2) s(-1) are obtained in monolayer and bulk samples, respectively. These
      results provide a foundation for understanding excitons in this new material and
      its optoelectronic applications. 

PMID- 25947346
TI  - Glutamate dehydrogenase is a novel prognostic marker and predicts metastases in
      colorectal cancer patients.
AB  - BACKGROUND: Glutamate dehydrogenase (GDH) is a key enzyme that catalyzes the
      final reaction of the glutamine metabolic pathway, and has been reported
      implicated in tumor growth and metastasis. However, it's clinical significance
      and role in colorectal cancer (CRC) pathogenesis is largely unknown. METHODS: The
      expression of GDH was determined by qPCR, western blot and immunohistochemistry
      in CRC cells and samples. The correlation of GDH expression with
      clinicopathologic features and prognosis was analyzed. The functional role of GDH
      in CRC cell proliferation, motility and metastasis was evaluated. RESULTS: We
      found that GDH was up-regulated both in colorectal cancer and metastatic lesions
      (n = 104). Patients with high GDH expression had poorer overall survival (HR
      2.32; 95% CI 1.26-4.26; P = 0.007) and poorer disease-free survival rates (HR
      2.48; 95% CI 1.25-4.92; P = 0.009) than those with low GDH expression.
      Furthermore, we showed that GDH expression was an independent prognostic factor
      for CRC. In addition, over-expression of GDH promoted cell proliferation,
      migration and invasion in vitro, whereas loss function of GDH did the opposite.
      Finally, we demonstrated that the promotion of CRC progression by GDH correlated
      with activation of STAT3 mediated epithelial-mesenchymal transition (EMT)
      induction. CONCLUSIONS: These results indicate that GDH plays a critical role in
      CRC progression, and may provide a novel metabolism therapeutic target for CRC
      treatment.

PMID- 25947348
TI  - Pulmonary embolism response teams.
AB  - OPINION STATEMENT: Pulmonary embolism (PE) is a complex and multidimensional
      pathophysiology, the diagnosis and management of which spans multiple
      disciplines. The high morbidity and associated mortality of "massive" and
      "submassive" acute PE may require prompt, definitive management; however, current
      consensus guidelines in this domain are not supported by high-level evidence.
      Randomized clinical trials comparing available pharmacologic and invasive
      treatment modalities-including anticoagulation, thrombolysis, and embolectomy
      have not been conducted and continue to be challenging to conceptualize, design,
      and execute. Consequently, time-sensitive therapeutic determinations are largely
      not standardized, and rendered on a case-by-case basis in part depending on
      institutional practices and expertises. Chronic sequelae of PE, such as chronic
      thromboembolic pulmonary hypertension and right heart failure, are increasingly
      identified as conditions necessitating longitudinal specialty care. These and
      other challenges have created a niche for a multidisciplinary team which can
      respond rapidly to unstable patient scenarios, appropriately deploy resources,
      and offer highly specialized acute and chronic management of PE. The
      Massachusetts General Hospital Pulmonary Embolism Response Team (PERT), modeled
      after existing rapid response and collaborative care teams, is a novel approach
      that combines this clinical service with the development of an educational and
      research framework to advance the care of patients with PE.

PMID- 25947349
TI  - Socio-economic, epidemiological and geographic features based on GIS-integrated
      mapping to identify malarial hotspots.
AB  - BACKGROUND: Malaria is a major health problem in the tropical and subtropical
      world. In India, 95% of the population resides in malaria endemic regions and it
      is major public health problem in most parts of the country. The present work has
      developed malaria maps by integrating socio-economic, epidemiology and
      geographical dimensions of three eastern districts of Uttar Pradesh, India. The
      area has been studied in each dimension separately, and later integrated to find
      a list of vulnerable pockets/villages, called as malarial hotspots. METHODS: The
      study has been done at village level. Seasonal variation of malaria, comparison
      of epidemiology indices and progress of the medical facility were studied. Ten
      independent geographical information system (GIS) maps of socio-economic aspects
      (population, child population, literacy, and work force participation),
      epidemiology (annual parasitic index (API) and slides collected and examined) and
      geographical features (settlement, forest cover, water bodies, rainfall, relative
      humidity, and temperature) were drawn and studied. These maps were overlaid based
      on computed weight matrix to find malarial hotspot. RESULTS: It was found that
      the studied dimensions were inter-weaving factors for malaria epidemic and
      closely affected malaria situations as evidenced from the obtained correlation
      matrix. The regions with water logging, high rainfall and proximity to forest,
      along with poor socio-economic conditions, are primarily hotspot regions. The
      work is presented through a series of GIS maps, tables, figures and graphs. A
      total of 2,054 out of 8,973 villages studied were found to be malarial hotspots
      and consequently suggestions were made to the concerned government malaria
      offices. CONCLUSION: With developing technology, information tools such as GIS,
      have captured almost every field of scientific research especially of vector
      borne diseases, such as malaria. Malarial mapping enables easy update of
      information and effortless accessibility of geo-referenced data to policy makers
      to produce cost-effective measures for malaria control in endemic regions.

PMID- 25947350
TI  - NMR assignment of the immune mapped protein 1 (IMP1) homologue from Plasmodium
      falciparum.
AB  - Plasmodium falciparum is responsible for causing cerebral malaria in humans. IMP1
      is an immunogenic protein, present in the parasite, which has been shown to
      induce an immune response against apicomplexan parasites in a species-specific
      manner. Here, we report the complete NMR assignments of PfIMP1. 

PMID- 25947351
TI  - Chemical shift assignments for S. cerevisiae Ubc13.
AB  - The ubiquitination pathway controls several human cellular processes, most
      notably protein degradation. Ubiquitin, a small signaling protein, is activated
      by the E1 activating enzyme, transferred to an E2 conjugating enzyme, and then
      attached to a target substrate through a process that can be facilitated by an E3
      ligase enzyme. The enzymatic mechanism of ubiquitin transfer from the E2
      conjugating enzyme onto substrate is not clear. The highly conserved HPN motif in
      E2 catalytic domains is generally thought to help stabilize an oxyanion
      intermediate formed during ubiquitin transfer. However recent work suggests this
      motif is instead involved in a structural, non-enzymatic role. As a platform to
      better understand the E2 catalyzed ubiquitin transfer mechanism, we determined
      the chemical shift assignments of S. cerevisiae E2 enzyme Ubc13. 

PMID- 25947353
TI  - Highly reliable switching via phase transition using hydrogen peroxide in
      homogeneous and multi-layered GaZnO(x)-based resistive random access memory
      devices.
AB  - Here, we propose an effective method for improving the resistive switching
      characteristics of solution-processed gallium-doped zinc oxide (GaZnO(x))
      resistive random access memory (RRAM) devices using hydrogen peroxide. Our
      results imply that solution processed GaZnO(x) RRAM devices could be one of the
      candidates for the development of low cost RRAM.

PMID- 25947352
TI  - Is risk-benefit of warfarin for atrial fibrillation with heart failure determined
      by heart failure severity?

PMID- 25947354
TI  - Ethics-sensitivity of the Ghana national integrated strategic response plan for
      pandemic influenza.
AB  - BACKGROUND: Many commentators call for a more ethical approach to planning for
      influenza pandemics. In the developed world, some pandemic preparedness plans
      have already been examined from an ethical viewpoint. This paper assesses the
      attention given to ethics issues by the Ghana National Integrated Strategic Plan
      for Pandemic Influenza (NISPPI). METHODS: We critically analyzed the Ghana
      NISPPI's sensitivity to ethics issues to determine how well it reflects ethical
      commitments and principles identified in our review of global pandemic
      preparedness literature, existing pandemic plans, and relevant ethics frameworks.
      RESULTS: This paper reveals that important ethical issues have not been addressed
      in the Ghana NISPPI. Several important ethical issues are unanticipated,
      unacknowledged, and unplanned for. These include guidelines on allocation of
      scarce resources, the duties of healthcare workers, ethics-sensitive operational
      guidelines/protocols, and compensation programs. The NISPPI also pays scant
      attention to use of vaccines and antivirals, border issues and cooperation with
      neighboring countries, justification for delineated actions, and outbreak
      simulations. Feedback and communication plans are nebulous, while leadership,
      coordination, and budgeting are quite detailed. With respect to presentation, the
      NISPPI's text is organized around five thematic areas. While each area implicates
      ethical issues, NISPPI treatment of these areas consistently fails to address
      them. CONCLUSIONS: Our analysis reveals a lack of consideration of ethics by the
      NISPPI. We contend that, while the plan's content and fundamental assumptions
      provide support for implementation of the delineated public health actions, its
      consideration of ethical issues is poor. Deficiencies include a failure to
      incorporate guidelines that ensure fair distribution of scarce resources and a
      lack of justification for delineated procedures. Until these deficiencies are
      recognized and addressed, Ghana runs the risk of rolling out unjust and ethically
      indefensible actions with real negative effects in the event of a pandemic.
      Soliciting inputs from the public and consultation with ethicists during the next
      revision of the NISPPI will be useful in addressing these issues.

PMID- 25947355
TI  - Controlled synthesis of bimetallic Pd-Rh nanoframes and nanoboxes with high
      catalytic performances.
AB  - Bimetallic nanoframes and nanoboxes of Pd-Rh are synthesized by selective removal
      of Pd cores from different Pd-Rh nanocubes prepared by a hydrothermal reaction of
      PdCl2, RhCl3 and HCHO. HCHO in the procedure alters the reaction kinetics and the
      growth behavior of Pd and Rh, resulting in different nanocubes that determine the
      following hollow nanostructures, nanoframes or nanoboxes. The catalytic
      properties of the hollow nanostructures are investigated using the oxidation of o
      phenylenediamine (OPDA) to 2,3-diaminophenazine (DAP) as a model reaction. The
      resulting bimetallic nanoframes and nanoboxes show enhanced conversion
      efficiencies compared to their solid counterparts. This method offers a
      convenient way for mass production of bimetallic hollow nanomaterials. 

PMID- 25947356
TI  - Factor XIII-A dynamics in acute myocardial infarction: a novel prognostic
      biomarker?
AB  - After acute myocardial infarction (MI) the damaged heart has to be repaired.
      Factor XIII (FXIII) is considered a key molecule in promoting heart healing.
      FXIII deficiency was associated to cardiac rupture and anomalous remodelling in
      MI. During MI, FXIII contributes firstly to the intracoronary thrombus formation
      and shortly after to heal the myocardial lesion. To quantify the real
      contribution of FXIII in this process, and to explore its possible prognostic
      role, we monitored the FXIII-A subunit levels in 350 acute MI patients during the
      first six days (d0-d5) plus a control at 30-60 days (d30). A one-year follow-up
      was performed for all the patients. A transient drop in the FXIII-A mean level
      was noted in the whole cohort of patients (FXIII-Ad0 99.48 +/- 30.5 vs FXIII-Ad5
      76.51 +/- 27.02; p< 0.0001). Interestingly, those who developed post-MI heart
      failure showed the highest drop (FXIII-Ad5 52.1 +/- 25.2) and they already
      presented with low levels at recruitment. Similarly, those who died showed the
      same FXIII-A dynamic (FXIII-Ad5 54.0 +/- 22.5). Conversely, patients who remained
      free of major adverse cardiac events, had lower consuming (FXIII-Ad0 103.6 +/-
      29.1 vs FXIII-Ad5 84.4 +/- 24.5; p< 0.0001). Interestingly, the FXIII-A drop was
      independent from the amount of injury assessed by TnT and CKMB levels. The
      survival analysis ascribed an increased probability of early death or heart
      failure inversely related to FXIII-A quartiles (FXIII-A25th< 59.5 %; hazard ratio
      4.25; 2.2-5.1; p< 0.0001). Different FXIII-A dynamics and levels could be
      utilised as early prognostic indicators during acute MI, revealing the individual
      potential to heal and suggesting tailored treatments to avoid heart failure or
      its extreme consequence.

PMID- 25947357
TI  - Multiscale fabrication of biomimetic scaffolds for tympanic membrane tissue
      engineering.
AB  - The tympanic membrane (TM) is a thin tissue able to efficiently collect and
      transmit sound vibrations across the middle ear thanks to the particular
      orientation of its collagen fibers, radiate on one side and circular on the
      opposite side. Through the combination of advanced scaffolds and autologous
      cells, tissue engineering (TE) could offer valuable alternatives to autografting
      in major TM lesions. In this study, a multiscale approach based on
      electrospinning (ES) and additive manufacturing (AM) was investigated to
      fabricate scaffolds, based on FDA approved copolymers, resembling the anatomic
      features and collagen fiber arrangement of the human TM. A single scale TM
      scaffold was manufactured using a custom-made collector designed to confer a
      radial macro-arrangement to poly(lactic-co-glycolic acid) electrospun fibers
      during their deposition. Dual and triple scale scaffolds were fabricated
      combining conventional ES with AM to produce poly(ethylene oxide
      terephthalate)/poly(butylene terephthalate) block copolymer scaffolds with
      anatomic-like architecture. The processing parameters were optimized for each
      manufacturing method and copolymer. TM scaffolds were cultured in vitro with
      human mesenchymal stromal cells, which were viable, metabolically active and
      organized following the anisotropic character of the scaffolds. The highest
      viability, cell density and protein content were detected in dual and triple
      scale scaffolds. Our findings showed that these biomimetic micro-patterned
      substrates enabled cell disposal along architectural directions, thus appearing
      as promising substrates for developing functional TM replacements via TE.

PMID- 25947359
TI  - An optimized method for (15)N R(1) relaxation rate measurements in non-deuterated
      proteins.
AB  - (15)N longitudinal relaxation rates are extensively used for the characterization
      of protein dynamics; however, their accurate measurement is hindered by
      systematic errors. (15)N CSA/(1)H-(15)N dipolar cross-correlated relaxation (CC)
      and amide proton exchange saturation transfer from water protons are the two main
      sources of systematic errors in the determination of (15)N R1 rates through (1)H
      (15)N HSQC-based experiments. CC is usually suppressed through a train of 180
      degrees  proton pulses applied during the variable (15)N relaxation period (T),
      which can perturb water magnetization. Thus CC cancellation is required in such a
      way as to minimize water saturation effects. Here we examined the level of water
      saturation during the T period caused by various types of inversion proton pulses
      to suppress CC: (I) amide-selective IBURP-2; (II) cosine-modulated IBURP-2; (III)
      Watergate-like blocks; and (IV) non-selective hard. We additionally demonstrate
      the effect of uncontrolled saturation of aliphatic protons on (15)N R1 rates. In
      this paper we present an optimized pulse sequence that takes into account the
      crucial effect of controlling also the saturation of the aliphatic protons during
      (15)N R1 measurements in non-deuterated proteins. We show that using cosine
      modulated IBURP-2 pulses spaced 40 ms to cancel CC in this optimized pulse
      program is the method of choice to minimize systematic errors coming from water
      and aliphatic protons saturation effects. 

PMID- 25947360
TI  - The survival advantage: Underlying mechanisms and extant limitations.
AB  - Recently, researchers have begun to investigate the function of memory in our
      evolutionary history. According to Nairne and colleagues (e.g., Nairne,
      Pandeirada, and Thompson, 2008; Nairne, Thompson, and Pandeirada, 2007), the best
      mnemonic strategy for learning lists of unrelated words may be one that addresses
      the same problems that our Pleistocene ancestors faced: fitness-relevant problems
      including securing food and water, as well as protecting themselves from
      predators. Survival processing has been shown to promote better recall and
      recognition memory than many well-known mnemonic strategies (e.g., pleasantness
      ratings, imagery, generation, etc.). However, the survival advantage does not
      extend to all types of stimuli and tasks. The current review presents research
      that has replicated Nairne et al.'s (2007) original findings, in addition to the
      research designs that fail to replicate the survival advantage. In other words,
      there are specific manipulations in which survival processing does not appear to
      benefit memory any more than other strategies. Potential mechanisms for the
      survival advantage are described, with an emphasis on those that are the most
      plausible. These proximate mechanisms outline the memory processes that may
      contribute to the advantage, although the ultimate mechanism may be the congruity
      between the survival scenario and Pleistocene problem-solving. 

PMID- 25947358
TI  - Alternative Treatments For Melanoma: Targeting BCL-2 Family Members to De-Bulk
      and Kill Cancer Stem Cells.
AB  - For the first time new treatments in melanoma have produced significant responses
      in advanced diseases, but 30-90% of melanoma patients do not respond or
      eventually relapse after the initial response to the current treatments. The
      resistance of these melanomas is likely due to tumor heterogeneity, which may be
      explained by models such as the stochastic, hierarchical, and phenotype-switching
      models. This review will discuss the recent advancements in targeting BCL-2
      family members for cancer treatments, and how this approach can be applied as an
      alternative option to combat melanoma, and overcome melanoma relapse or
      resistance in current treatment regimens. 

PMID- 25947361
TI  - Simultaneous Determination and Pharmacokinetics of Metolazone, Losartan and
      Losartan Carboxylic Acid in Rat Plasma by HPLC-ESI-MS-MS.
AB  - For the first time, we developed and validated a highly sensitive, selective and
      rapid HPLC-ESI-MS-MS method for simultaneous quantification of metolazone (MET),
      losartan (LOS) and its metabolite losartan carboxylic acid (LCA) in rat plasma.
      After solid-phase extraction, the analytes and internal standard (irbesartan)
      were extracted from 100 uL plasma sample on an Agilent Poroshell 120, EC-C18 (50
      * 4.6 mm, i.d., 2.7 um) column using 5 uL injection volume with a total run time
      of 3 min. Acidified methanol/water mixture was used as a mobile phase. The parent
      -> product ion transitions for MET (m/z 366.0 -> 258.9), LOS (m/z 423.2 ->
      207.0), LCA (m/z 437.0 -> 235.1) and IS (m/z 429.2 -> 207.0) were monitored on a
      triple quadrupole mass spectrometer, operating in the multiple reaction
      monitoring and positive ion mode. The method was found to be linear in the range
      of 0.05-250 for MET, 2-3,000 for LOS and 4-3,500 ng/mL for LCA. The method was
      validated with respect to selectivity, linearity, accuracy, precision, recovery
      and stability according to accepted regulatory guidelines. The described method
      was successfully applied to preclinical pharmacokinetic studies of analytes after
      an oral administration of mixture of MET (1 mg/kg) and LOS (10 mg/kg) in rats. 

PMID- 25947362
TI  - Simultaneous Determination of 16 Nucleosides and Nucleobases in Euryale ferox
      Salisb. by Liquid Chromatography Coupled with Electro Spray Ionization Tandem
      Triple Quadrupole Mass Spectrometry (HPLC-ESI-TQ-MS/MS) in Multiple Reaction
      Monitoring (MRM) Mode.
AB  - In this study, a simple, rapid, efficient analytical method was established for
      the qualification and quantification of 16 nucleosides and nucleobases in Euryale
      ferox Salisb. by using liquid chromatography coupled with electrospray ionization
      tandem triple quadrupole mass spectrometry (HPLC-ESI-TQ-MS/MS) in multiple
      reaction monitoring (MRM) mode. Ideal separation of 16 target compounds was
      achieved on Xbridge Amide HILIC column (4.6 * 150 mm, 3.5 MUm) with gradient
      elution in 11 min by optimized conditions. Variations of nucleosides and
      nucleobase in samples from different cultivation regions ranging from 190.50 to
      1594.30 MUg/g were obvious. The total nucleoside contents were higher than total
      nucleobases, especially in the compositions of guanosine, cytidine and 2'
      deoxyguanosine. Samples 1-18 with dense thorns were better characters than
      samples 19-26 without thorns in terms of nucleosides and nucleobases
      concentrations in general. The limits of detection (LODs) and quantification
      (LOQs) for 16 analytical substances were investigated to be 0.11-6.33 ng/mL and
      0.35-21.1 ng/mL, respectively. And the method was first applied to large aquatic
      plants with good linearity, precision, repeatability and accuracy. All present
      information provided a scientific and rational reference for quality assessment
      and control of Euryale ferox Salisb. 

PMID- 25947364
TI  - Direct and indirect exposure to violence and psychological distress among civil
      servants in Rio de Janeiro, Brazil: a prospective cohort study.
AB  - BACKGROUND: Important social and economic changes accompanying the recent fast
      rate of urbanization have been considered a major factor in triggering and
      sustaining urban violence in Brazil. The purpose of this paper is to investigate
      the effects of exposure to direct, indirect, and contextual violence on the risk
      of psychological distress. METHODS: Prospective longitudinal study carried out
      among 3,058 civil servants working at university campuses in Rio de Janeiro.
      Psychological distress was measured using the General Health Questionnaire, and
      exposure to individual violence was assessed as direct (DV), indirect (IV), and
      both direct and indirect (DIV). Contextual violence was assessed through the
      geocoding of residential addresses of study participants and the rates of
      homicides in 2005 at the corresponding weighting area. Multiple logistic
      regression was used to evaluate individual and contextual correlates of
      psychological distress. RESULTS: Exposure to DIV increased more than six times
      (95% CI 2.7-16.0) the odds of psychological distress occurrence at the six-year
      follow-up. Regarding persistence of psychological distress, the association with
      violence exposure was 1.6 (95% CI 1.0-2.4) for DV and 2.7 (95% CI 1.3-5.3) for
      IV. Contextual violence was not associated with psychological distress, and no
      interaction effect was found between exposure to individual and contextual
      violence in the occurrence/persistence of psychological distress. CONCLUSIONS:
      Results of this study highlight the importance of assessing multiple forms of
      violence in research on the social determinants of mental disorders and support
      the view that individual exposure to different forms of violence increases the
      risk of psychological distress.

PMID- 25947365
TI  - A study on use of animals as traditional medicine by Sukuma Tribe of Busega
      District in North-western Tanzania.
AB  - BACKGROUND: Faunal resources have played an extensive range of roles in human
      life from the initial days of recorded history. In addition to their importance,
      animals have been acknowledged in religion, art, music and literature and several
      other different cultural manifestations of mankind. Human beings are acquainted
      with use of animals for foodstuff, cloth, medicine, etc. since ancient times.
      Huge work has been carried out on ethnobotany and traditional medicine. Animal
      and their products are also holding medicinal properties that can be exploited
      for the benefit of human beings like plants. In Tanzania, many tribal communities
      are spread all over the country and these people are still totally depended on
      local customary medicinal system for their health care. In the world Tanzania is
      gifted with wide range of floral and faunal biodiversity. The use of traditional
      medicine from animals by Sukuma ethnic group of Busega district is the aim of the
      present study. METHOD: In order to collect the information on ethnozoological use
      about animal and their products predominant among this tribe in Busega district,
      a study was carried out from August 2012, to July 2013. Data were collected
      through semi-structured questionnaire and open interview with 180 (118 male and
      62 females) selected people. The people from whom the data were collected
      comprise old age community members, traditional health practicener, fishermen and
      cultural officers. The name of animal and other ethnozoological information were
      documented. Pictures and discussion were also recorded with the help of camera
      and voice recorder. RESULT: A total of 42 various animal species were used in
      nearly 30 different medicinal purposes including STD, stoppage of bleeding,
      reproductive disorders, asthma, weakness, tuberculosis, cough, paralysis and
      wound and for other religious beliefs. It has been noticed that animal used by
      Sukuma tribe, comprise of seventeen mammals, seven birds, four reptiles, eight
      arthropods and two mollusks. Some of the protected species were also used as
      important medicinal resources. We also found that cough, tuberculosis, asthma and
      other respiratory diseases are the utmost cited disease, as such, a number of
      traditional medicines are available for the treatment. CONCLUSIONS: The present
      work indicates that 42 animal species were being used to treat nearly 30
      different ailments and results show that ethnozoological practices are an
      important alternative medicinal practice by the Sukuma tribe living in Bungesa
      district. The present study also indicates the very rich ethnozoological
      knowledge of these people in relation to traditional medicine. So there is a
      critical need to properly document to keep a record of the ethnozoological
      information. We hope that the information generated in this study will be useful
      for further research in the field of ethnozoology, ethnopharmacology and
      conservation approach.

PMID- 25947366
TI  - Soluble EpCAM levels in ascites correlate with positive cytology and neutralize
      catumaxomab activity in vitro.
AB  - BACKGROUND: EpCAM is highly expressed on membrane of epithelial tumor cells and
      has been detected as soluble/secreted (sEpCAM) in serum of cancer patients. In
      this study we established an ELISA for in vitro diagnostics to measure sEpCAM
      concentrations in ascites. Moreover, we evaluated the influence of sEpCAM levels
      on catumaxomab (antibody)--dependent cellular cytotoxicity (ADCC). METHODS:
      Ascites specimens from cancer patients with positive (C+, n = 49) and negative (C
      , n = 22) cytology and ascites of patients with liver cirrhosis (LC, n = 31) were
      collected. All cell-free plasma samples were analyzed for sEpCAM levels with a
      sandwich ELISA system established and validated by a human recombinant EpCAM
      standard for measurements in ascites as biological matrix. In addition, we
      evaluated effects of different sEpCAM concentrations on catumaxomab-dependent
      cell-mediated cytotoxicity (ADCC) with human peripheral blood mononuclear cells
      (PBMNCs) and human tumor cells. RESULTS: Our ELISA showed a high specificity for
      secreted EpCAM as determined by control HEK293FT cell lines stably expressing
      intracellular (EpICD), extracellular (EpEX) and the full-length protein (EpCAM)
      as fusion proteins. The lower limit of quantification was 200 pg/mL and the
      linear quantification range up to 5,000 pg/mL in ascites as biological matrix.
      Significant levels of sEpCAM were found in 39% of C+, 14% of C- and 13% of LC
      ascites samples. Higher concentrations of sEpCAM were detectable in C+ (mean:
      1,015 pg/mL) than in C- (mean: 449 pg/mL; p = 0.04) or LC (mean: 326 pg/mL; p =
      0.01). Soluble EpCAM concentration of 1 ng/mL significantly inhibited ADCC of
      PBMNCs on EpCAM overexpressing target cells. CONCLUSION: Elevated concentrations
      of sEpCAM can be found in a subgroup of C+ and also in a small group of C-
      patients. We consider that sEpCAM levels in different tumor entities and
      individual patients should be evaluated prior to applying anti-EpCAM antibody
      based cancer therapies, since sEpCAM neutralizes catumaxomab activity, making
      therapy less efficient.

PMID- 25947367
TI  - Impact of special patient populations on the pharmacokinetics of echinocandins.
AB  - Echinocandins belong to the class of antifungal agents. Currently, three
      echinocandin drugs are licensed for intravenous treatment of invasive fungal
      infections: anidulafungin, caspofungin and micafungin. While their antifungal
      activity overlaps, there are substantial differences in pharmacokinetics (PK).
      Numerous factors may account for variability in PK of echinocandins including age
      (pediatrics vs adults), body surface area and body composition (normal weight vs
      obesity), disease status (e.g., critically ill and burn patients) and organ
      dysfunction (kidney and liver impairment). Subsequent effects of altered exposure
      might impact efficacy and safety. Knowledge of PK behavior is crucial in optimal
      clinical utilization of echinocandin in a specific patient or patient population.
      This review provides up-to-date information on PK data of anidulafungin,
      caspofungin and micafungin in special patient populations. Patient populations
      addressed are neonates, children and adolescents, obese patients, patients with
      hepatic or renal impairment, critically ill patients (including burn patients)
      and patients with hematological diseases. 

PMID- 25947368
TI  - Surface lattice resonances and magneto-optical response in magnetic nanoparticle
      arrays.
AB  - Structuring metallic and magnetic materials on subwavelength scales allows for
      extreme confinement and a versatile design of electromagnetic field modes. This
      may be used, for example, to enhance magneto-optical responses, to control
      plasmonic systems using a magnetic field, or to tailor magneto-optical properties
      of individual nanostructures. Here we show that periodic rectangular arrays of
      magnetic nanoparticles display surface plasmon modes in which the two directions
      of the lattice are coupled by the magnetic field-controllable spin-orbit coupling
      in the nanoparticles. When breaking the symmetry of the lattice, we find that the
      optical response shows Fano-type surface lattice resonances whose frequency is
      determined by the periodicity orthogonal to the polarization of the incident
      field. In striking contrast, the magneto-optical Kerr response is controlled by
      the period in the parallel direction. The spectral separation of the response for
      longitudinal and orthogonal excitations provides versatile tuning of narrow and
      intense magneto-optical resonances. 

PMID- 25947370
TI  - Influence of dose-death interval on colchicine and metabolite distribution in
      decomposed skeletal tissues.
AB  - The semi-quantitative analysis of decomposed bone of rats exposed to colchicine
      and euthanized following different time intervals postexposure (i.e., dose-death
      interval, DDI) is described. Rats received colchicine (50 mg/kg, i.p.) and were
      euthanized 30 min (DDI1; n = 4), 60 min (DDI2; n = 4), or 180 min (DDI3; n = 4)
      postdose. Drug-free animals (n = 3) served as negative controls. Perimortem heart
      plasma was collected. Remains were decomposed to skeleton outdoors and then
      collected and sorted (skull, vertebrae, rib, pelvis, femur, tibia). Bones were
      dried, pulverized, and prepared by microwave-assisted extraction and microplate
      solid-phase extraction (MAE-MPSPE), followed by analysis for colchicine, 3
      demethylcolchicine (3DMC), and 2-demethylcolchicine (2DMC) by ultra-high
      performance liquid chromatography with photodiode array detection (UHPLC-PDA) at
      350 nm. Bone type was a main effect (Kruskall-Wallis, p < 0.05) with respect to
      drug level (expressed as mass-normalized response ratio, RR/m) for each analyte,
      at each DDI. For all samples, DDI was a main effect (Kruskall-Wallis, p < 0.05)
      with respect to analyte level, and the ratio of analyte levels (RR3DMC/RRCOLCH,
      RR2DMC/RRCOLCH, and RR2DMC/RR3DMC). Bone COLCH levels varied by 19-fold, 12-fold,
      and 60-fold across all bone types in the DDI1, DDI2, and DDI3 groups,
      respectively. Bone 3DMC levels varied by 12-fold, 11-fold and 17-fold across all
      bone types in the DDI1, DDI2, and DDI3 groups, respectively. Bone 2DMC levels
      varied by 20-fold, 14-fold, and 14-fold across all bone types in the DDI1, DDI2,
      and DDI3 groups, respectively. Values of RR3DMC/RRCOLCH varied by 16-fold, 5
      fold, and 5-fold across all bone types in the DDI1, DDI2, and DDI3 groups,
      respectively. Values of RR2DMC/RRCOLCH varied by 10-fold, 6-fold, and 12-fold
      across all bone types in the DDI1, DDI2, and DDI3 groups, respectively. Values of
      RR2DMC/RR3DMC varied by 3-fold, 5-fold, and 2-fold across all bone types in the
      DDI1, DDI2, and DDI3 groups, respectively. Measured analyte levels in bone
      correlated poorly with corresponding levels in blood (r = -0.65-+0.31). Measured
      values of RR2DMC/RRCOLCH and RR2DMC/RR3DMC in bone also correlated poorly with
      corresponding values in blood. Measured values of RR3DMC/RRCOLCH were well
      correlated with corresponding blood levels for all bone types except skull (r =
      0.91-0.97).

PMID- 25947371
TI  - Introducing qualitatively-driven mixed-method designs.

PMID- 25947369
TI  - The Glymphatic System: A Beginner's Guide.
AB  - The glymphatic system is a recently discovered macroscopic waste clearance system
      that utilizes a unique system of perivascular tunnels, formed by astroglial
      cells, to promote efficient elimination of soluble proteins and metabolites from
      the central nervous system. Besides waste elimination, the glymphatic system also
      facilitates  brain-wide distribution of several compounds, including glucose,
      lipids, amino acids, growth factors, and neuromodulators. Intriguingly, the
      glymphatic system function mainly during sleep and is largely disengaged during
      wakefulness. The biological need for sleep across all species may therefore
      reflect that the brain must enter a state of activity that enables elimination of
      potentially neurotoxic waste products, including beta-amyloid. Since the concept
      of the glymphatic system is relatively new, we will here review its basic
      structural elements, organization, regulation, and functions. We will also
      discuss recent studies indicating that glymphatic function is suppressed in
      various diseases and that failure of glymphatic function in turn might contribute
      to pathology in neurodegenerative disorders, traumatic brain injury and stroke. 

PMID- 25947372
TI  - Metallothionein-I/II Promotes Axonal Regeneration in the Central Nervous System.
AB  - The adult CNS does not spontaneously regenerate after injury, due in large part
      to myelin-associated inhibitors such as myelin-associated glycoprotein (MAG),
      Nogo-A, and oligodendrocyte-myelin glycoprotein. All three inhibitors can
      interact with either the Nogo receptor complex or paired immunoglobulin-like
      receptor B. A conditioning lesion of the sciatic nerve allows the central
      processes of dorsal root ganglion (DRG) neurons to spontaneously regenerate in
      vivo after a dorsal column lesion. After a conditioning lesion, DRG neurons are
      no longer inhibited by myelin, and this effect is cyclic AMP (cAMP)- and
      transcription-dependent. Using a microarray analysis, we identified several genes
      that are up-regulated both in adult DRGs after a conditioning lesion and in DRG
      neurons treated with cAMP analogues. One gene that was up-regulated under both
      conditions is metallothionein (MT)-I. We show here that treatment with two
      closely related isoforms of MT (MT-I/II) can overcome the inhibitory effects of
      both myelin and MAG for cortical, hippocampal, and DRG neurons. Intrathecal
      delivery of MT-I/II to adult DRGs also promotes neurite outgrowth in the presence
      of MAG. Adult DRGs from MT-I/II-deficient mice extend significantly shorter
      processes on MAG compared with wild-type DRG neurons, and regeneration of dorsal
      column axons does not occur after a conditioning lesion in MT-I/II-deficient
      mice. Furthermore, a single intravitreal injection of MT-I/II after optic nerve
      crush promotes axonal regeneration. Mechanistically, MT-I/II ability to overcome
      MAG-mediated inhibition is transcription-dependent, and MT-I/II can block the
      proteolytic activity of alpha-secretase and the activation of PKC and Rho in
      response to soluble MAG. 

PMID- 25947373
TI  - Soluble Human Cytomegalovirus gH/gL/pUL128-131 Pentameric Complex, but Not gH/gL,
      Inhibits Viral Entry to Epithelial Cells and Presents Dominant Native
      Neutralizing Epitopes.
AB  - Congenital infection of human cytomegalovirus (HCMV) is one of the leading causes
      of nongenetic birth defects, and development of a prophylactic vaccine against
      HCMV is of high priority for public health. The gH/gL/pUL128-131 pentameric
      complex mediates HCMV entry into endothelial and epithelial cells, and it is a
      major target for neutralizing antibody responses. To better understand the
      mechanism by which antibodies interact with the epitopes of the gH/gL/pUL128-131
      pentameric complex resulting in viral neutralization, we expressed and purified
      soluble gH/gL/pUL128-131 pentameric complex and gH/gL from Chinese hamster ovary
      cells to >95% purity. The soluble gH/gL, which exists predominantly as (gH/gL)2
      homodimer with a molecular mass of 220 kDa in solution, has a stoichiometry of
      1:1 and a pI of 6.0-6.5. The pentameric complex has a molecular mass of 160 kDa,
      a stoichiometry of 1:1:1:1:1, and a pI of 7.4-8.1. The soluble pentameric
      complex, but not gH/gL, adsorbs 76% of neutralizing activities in HCMV human
      hyperimmune globulin, consistent with earlier reports that the most potent
      neutralizing epitopes for blocking epithelial infection are unique to the
      pentameric complex. Functionally, the soluble pentameric complex, but not gH/gL,
      blocks viral entry to epithelial cells in culture. Our results highlight the
      importance of the gH/gL/pUL128-131 pentameric complex in HCMV vaccine design and
      emphasize the necessity to monitor the integrity of the pentameric complex during
      the vaccine manufacturing process. 

PMID- 25947374
TI  - Roles of Residues Arg-61 and Gln-38 of Human DNA Polymerase eta in Bypass of
      Deoxyguanosine and 7,8-Dihydro-8-oxo-2'-deoxyguanosine.
AB  - Like the other Y-family DNA polymerases, human DNA polymerase eta (hpol eta) has
      relatively low fidelity and is able to tolerate damage during DNA synthesis,
      including 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxoG), one of the most abundant
      DNA lesions in the genome. Crystal structures show that Arg-61 and Gln-38 are
      located near the active site and may play important roles in the fidelity and
      efficiency of hpol eta. Site-directed mutagenesis was used to replace these side
      chains either alone or together, and the wild type or mutant proteins were
      purified and tested by replicating DNA past deoxyguanosine (G) or 8-oxoG. The
      catalytic activity of hpol eta was dramatically disrupted by the R61M and
      Q38A/R61A mutations, as opposed to the R61A and Q38A single mutants. Crystal
      structures of hpol eta mutant ternary complexes reveal that polarized water
      molecules can mimic and partially compensate for the missing side chains of Arg
      61 and Gln-38 in the Q38A/R61A mutant. The combined data indicate that the
      positioning and positive charge of Arg-61 synergistically contribute to the
      nucleotidyl transfer reaction, with additional influence exerted by Gln-38. In
      addition, gel filtration chromatography separated multimeric and monomeric forms
      of wild type and mutant hpol eta, indicating the possibility that hpol eta forms
      multimers in vivo. 

PMID- 25947376
TI  - Introduction to Thematic Minireview Series: Novel Bioactive Sphingolipids.
AB  - Sphingosine was named by J. L. W. Thudichum for its enigmatic properties. This
      descriptor has applied to sphingolipids for over a century because new enigmas
      continue to surface. This JBC minireview series presents articles about three
      novel subspecies of sphingolipids, alpha-galactosylceramides, 4,5
      dihydroceramides, and 1-deoxysphingolipids, that have important activities but,
      until recently, remained undetected (or at least understudied) in the shadow of
      very closely related compounds. They also serve as a reminder that important
      metabolites still lie "off the radar screen" in reports of global and
      comprehensive metabolomic profiling. 

PMID- 25947375
TI  - Phospholipid Flippase ATP10A Translocates Phosphatidylcholine and Is Involved in
      Plasma Membrane Dynamics.
AB  - We showed previously that ATP11A and ATP11C have flippase activity toward
      aminophospholipids (phosphatidylserine (PS) and phosphatidylethanolamine (PE))
      and ATP8B1 and that ATP8B2 have flippase activity toward phosphatidylcholine (PC)
      (Takatsu, H., Tanaka, G., Segawa, K., Suzuki, J., Nagata, S., Nakayama, K., and
      Shin, H. W. (2014) J. Biol. Chem. 289, 33543-33556). Here, we show that the
      localization of class 5 P4-ATPases to the plasma membrane (ATP10A and ATP10D) and
      late endosomes (ATP10B) requires an interaction with CDC50A. Moreover, exogenous
      expression of ATP10A, but not its ATPase-deficient mutant ATP10A(E203Q),
      dramatically increased PC flipping but not flipping of PS or PE. Depletion of
      CDC50A caused ATP10A to be retained at the endoplasmic reticulum instead of being
      delivered to the plasma membrane and abrogated the increased PC flipping activity
      observed by expression of ATP10A. These results demonstrate that ATP10A is
      delivered to the plasma membrane via its interaction with CDC50A and,
      specifically, flips PC at the plasma membrane. Importantly, expression of ATP10A,
      but not ATP10A(E203Q), dramatically altered the cell shape and decreased cell
      size. In addition, expression of ATP10A, but not ATP10A(E203Q), delayed cell
      adhesion and cell spreading onto the extracellular matrix. These results suggest
      that enhanced PC flipping activity due to exogenous ATP10A expression alters the
      lipid composition at the plasma membrane, which may in turn cause a delay in cell
      spreading and a change in cell morphology. 

PMID- 25947377
TI  - Dihydroceramides: From Bit Players to Lead Actors.
AB  - Sphingolipid synthesis involves a highly conserved biosynthetic pathway that
      produces fundamental precursors of complex sphingolipids. The final reaction
      involves the insertion of a double bond into dihydroceramides to generate the
      more abundant ceramides, which are converted to sphingomyelins and
      glucosylceramides/gangliosides by the addition of polar head groups. Although
      ceramides have long been known to mediate cellular stress responses, the
      dihydroceramides that are transiently produced during de novo sphingolipid
      synthesis were deemed inert. Evidence published in the last few years suggests
      that these dihydroceramides accumulate to a far greater extent in tissues than
      previously thought. Moreover, they have biological functions that are distinct
      and non-overlapping with those of the more prevalent ceramides. Roles are being
      uncovered in autophagy, hypoxia, and cellular proliferation, and the lipids are
      now implicated in the etiology, treatment, and/or diagnosis of diabetes, cancer,
      ischemia/reperfusion injury, and neurodegenerative diseases. This minireview
      summarizes recent findings on this emerging class of bioactive lipids. 

PMID- 25947378
TI  - The Alpha and Omega of Galactosylceramides in T Cell Immune Function.
AB  - Glycosphingolipids are a subgroup of glycolipids that contain an amino alcohol
      sphingoid base linked to sugars. They are found in the membranes of cells ranging
      from bacteria to vertebrates. This group of lipids is known to stimulate the
      immune system through activation of a type of white blood cell known as natural
      killer T cell (NKT cell). Here we summarize the extensive research that has been
      done to identify the structures of natural glycolipids that stimulate NKT cells
      and to determine how these antigens are recognized. We also review studies
      designed to understand how glycolipid variants, both natural and synthetic, can
      alter the responses of NKT cells, leading to dramatic changes in the global
      immune response. 

PMID- 25947379
TI  - 1-Deoxysphingolipids Encountered Exogenously and Made de Novo: Dangerous
      Mysteries inside an Enigma.
AB  - The traditional backbones of mammalian sphingolipids are 2-amino, 1,3-diols made
      by serine palmitoyltransferase (SPT). Many organisms additionally produce non
      traditional, cytotoxic 1-deoxysphingoid bases and, surprisingly, mammalian SPT
      biosynthesizes some of them, too (e.g. 1-deoxysphinganine from L-alanine). These
      are rapidly N-acylated to 1-deoxy-"ceramides" with very uncommon biophysical
      properties. The functions of 1-deoxysphingolipids are not known, but they are
      certainly dangerous as contributors to sensory and autonomic neuropathies when
      elevated by inherited SPT mutations, and they are noticeable in diabetes, non
      alcoholic steatohepatitis, serine deficiencies, and other diseases. As components
      of food as well as endogenously produced, these substances are mysteries within
      an enigma.

PMID- 25947380
TI  - The Tyrosine Kinase c-Src Specifically Binds to the Active Integrin alphaIIbbeta3
      to Initiate Outside-in Signaling in Platelets.
AB  - It is currently believed that inactive tyrosine kinase c-Src in platelets binds
      to the cytoplasmic tail of the beta3 integrin subunit via its SH3 domain.
      Although a recent NMR study supports this contention, it is likely that such
      binding would be precluded in inactive c-Src because an auto-inhibitory linker
      physically occludes the beta3 tail binding site. Accordingly, we have re-examined
      c-Src binding to beta3 by immunoprecipitation as well as NMR spectroscopy. In
      unstimulated platelets, we detected little to no interaction between c-Src and
      beta3. Following platelet activation, however, c-Src was co-immunoprecipitated
      with beta3 in a time-dependent manner and underwent progressive activation as
      well. We then measured chemical shift perturbations in the (15)N-labeled SH3
      domain induced by the C-terminal beta3 tail peptide NITYRGT and found that the
      peptide interacted with the SH3 domain RT-loop and surrounding residues. A
      control peptide whose last three residues where replaced with those of the beta1
      cytoplasmic tail induced only small chemical shift perturbations on the opposite
      face of the SH3 domain. Next, to mimic inactive c-Src, we found that the
      canonical polyproline peptide RPLPPLP prevented binding of the beta3 peptide to
      the RT- loop. Under these conditions, the beta3 peptide induced chemical shift
      perturbations similar to the negative control. We conclude that the primary
      interaction of c-Src with the beta3 tail occurs in its activated state and at a
      site that overlaps with PPII binding site in its SH3 domain. Interactions of
      inactive c-Src with beta3 are weak and insensitive to beta3 tail mutations. 

PMID- 25947381
TI  - Impact of Exogenous Galectin-9 on Human T Cells: CONTRIBUTION OF THE T CELL
      RECEPTOR COMPLEX TO ANTIGEN-INDEPENDENT ACTIVATION BUT NOT TO APOPTOSIS
      INDUCTION.
AB  - Galectin-9 (gal-9) is a multifunctional beta-galactoside-binding lectin,
      frequently released in the extracellular medium, where it acts as a pleiotropic
      immune modulator. Despite its overall immunosuppressive effects, a recent study
      has reported bimodal action of gal-9 on human resting blood T cells with
      apoptosis occurring in the majority of them, followed by a wave of activation and
      expansion of Th1 cells in the surviving population. Our knowledge of the
      signaling events triggered by exogenous gal-9 in T cells remains limited. One of
      these events is cytosolic calcium (Ca(2+)) release reported in some murine and
      human T cells. The aim of this study was to investigate the contribution of
      Ca(2+) mobilization to apoptotic and nonapoptotic effects of exogenous gal-9 in
      human T cells. We found that the T cell receptor (TCR)-CD3 complex and the Lck
      kinase were required for Ca(2+) mobilization but not for apoptosis induction in
      Jurkat cells. These data were confirmed in human CD4(+) T cells from peripheral
      blood as follows: a specific Lck chemical inhibitor abrogated Ca(2+) mobilization
      but not apoptosis induction. Moreover, Lck activity was also required for the
      production of Th1-type cytokines, i.e. interleukin-2 and interferon-gamma, which
      resulted from gal-9 stimulation in peripheral CD4(+) T cells. These findings
      indicate that gal-9 acts on T cells by two distinct pathways as follows: one
      mimicking antigen-specific activation of the TCR with a mandatory contribution of
      proximal elements of the TCR complex, especially Lck, and another resulting in
      apoptosis that is independent of this complex. 

PMID- 25947383
TI  - Feedback Control of Snf1 Protein and Its Phosphorylation Is Necessary for
      Adaptation to Environmental Stress.
AB  - Snf1, a member of the AMP-activated protein kinase family, plays a critical role
      in metabolic energy control in yeast cells. Snf1 activity is activated by
      phosphorylation of Thr-210 on the activation loop of its catalytic subunit;
      following activation, Snf1 regulates stress-responsive transcription factors.
      Here, we report that the level of Snf1 protein is dramatically decreased in a
      UBP8- and UBP10-deleted yeast mutant (ubp8Delta ubp10Delta), and this is
      independent of transcriptional regulation and proteasome-mediated degradation.
      Surprisingly, most Snf1-mediated functions, including glucose limitation
      regulation, utilization of alternative carbon sources, stress responses, and
      aging, are unaffected in this strain. Snf1 phosphorylation in ubp8Delta
      ubp10Delta cells is hyperactivated upon stress, which may compensate for the loss
      of the Snf1 protein and protect cells against stress and aging. Furthermore,
      artificial elevation of Snf1 phosphorylation (accomplished through deletion of
      REG1, which encodes a protein that regulates Snf1 dephosphorylation) restored
      Snf1 protein levels and the regulation of Snf1 activity in ubp8Delta ubp10Delta
      cells. Our results reveal the existence of a feedback loop that controls Snf1
      protein level and its phosphorylation, which is masked by Ubp8 and Ubp10 through
      an unknown mechanism. We propose that this dynamic modulation of Snf1
      phosphorylation and its protein level may be important for adaptation to
      environmental stress. 

PMID- 25947386
TI  - Selenium as an antidote in the treatment of mercury intoxication.
AB  - Selenium (Se) is an essential trace element for humans. It is found in the enzyme
      glutathione peroxidase. This enzyme protects the organism against certain types
      of damage. Some data suggest that Se plays a role in the body's metabolism of
      mercury (Hg). Selenium has in some studies been found to reduce the toxicity of
      Hg salts. Selenium and Hg bind in the body to each other. It is not totally clear
      what impact the amount of Se has in the human body on the metabolism and toxicity
      of prolonged Hg exposure. 

PMID- 25947382
TI  - Procollagen C-endopeptidase Enhancer Protein 2 (PCPE2) Reduces Atherosclerosis in
      Mice by Enhancing Scavenger Receptor Class B1 (SR-BI)-mediated High-density
      Lipoprotein (HDL)-Cholesteryl Ester Uptake.
AB  - Studies in human populations have shown a significant correlation between
      procollagen C-endopeptidase enhancer protein 2 (PCPE2) single nucleotide
      polymorphisms and plasma HDL cholesterol concentrations. PCPE2, a 52-kDa
      glycoprotein located in the extracellular matrix, enhances the cleavage of C
      terminal procollagen by bone morphogenetic protein 1 (BMP1). Our studies here
      focused on investigating the basis for the elevated concentration of enlarged
      plasma HDL in PCPE2-deficient mice to determine whether they protected against
      diet-induced atherosclerosis. PCPE2-deficient mice were crossed with LDL receptor
      deficient mice to obtain LDLr(-/-), PCPE2(-/-) mice, which had elevated HDL
      levels compared with LDLr(-/-) mice with similar LDL concentrations. We found
      that LDLr(-/-), PCPE2(-/-) mice had significantly more neutral lipid and CD68+
      infiltration in the aortic root than LDLr(-/-) mice. Surprisingly, in light of
      their elevated HDL levels, the extent of aortic lipid deposition in LDLr(-/-),
      PCPE2(-/-) mice was similar to that reported for LDLr(-/-), apoA-I(-/-) mice,
      which lack any apoA-I/HDL. Furthermore, LDLr(-/-), PCPE2(-/-) mice had reduced
      HDL apoA-I fractional clearance and macrophage to fecal reverse cholesterol
      transport rates compared with LDLr(-/-) mice, despite a 2-fold increase in liver
      SR-BI expression. PCPE2 was shown to enhance SR-BI function by increasing the
      rate of HDL-associated cholesteryl ester uptake, possibly by optimizing SR-BI
      localization and/or conformation. We conclude that PCPE2 is atheroprotective and
      an important component of the reverse cholesterol transport HDL system. 

PMID- 25947387
TI  - Metallothionein, essential elements and lipid peroxidation in mercury-exposed
      suckling rats pretreated with selenium.
AB  - Detoxification of mercury (Hg) with selenium (Se) in the early postnatal period
      with regard to the expression of metallothionein protein (MT), essential element
      status, and lipid peroxidation level in tissues has not been studied. Seven-day
      old Wistar pups were orally pretreated with Se [6 MUmol Na2SeO3/kg body weight
      (b.w.)] for 3 days and then cotreated with Hg (6 MUmol HgCl2/kg b.w.) for the
      following 4 days. This group (Se + Hg) was compared to the groups treated with
      Hg, Se, or vehicle (control). Compared to the Hg-group, Se + Hg-group exhibited
      lower renal MT expression, reduced accumulation of Hg, Cu and Zn, and reduced
      excretion of Se, Hg and Zn in urine. In the liver, MT was stimulated by Se
      treatment in both, Se and Se + Hg-group. Hepatic and brain levels of the
      endogenous essential elements Cu, Fe, Mg, and Zn remained unchanged in all of the
      studied groups. Brain Hg levels and oxidation of lipids measured as
      thiobarbituric acid reactive substances were diminished in Se + Hg-group of pups
      compared to the Hg-group. This study suggests that Se pretreatment can help
      reduce Hg in the tissues of suckling rats, simultaneously preventing impairment
      of essential element levels in the kidneys and their excessive excretion via
      urine. Also, Se was shown to prevent oxidative damage of lipids in the brain,
      which is particularly susceptible to Hg during the early postnatal period.

PMID- 25947384
TI  - YidC/Alb3/Oxa1 Family of Insertases.
AB  - The YidC/Alb3/Oxa1 family functions in the insertion and folding of proteins in
      the bacterial cytoplasmic membrane, the chloroplast thylakoid membrane, and the
      mitochondrial inner membrane. All members share a conserved region composed of
      five transmembrane regions. These proteins mediate membrane insertion of an
      assorted group of proteins, ranging from respiratory subunits in the mitochondria
      and light-harvesting chlorophyll-binding proteins in chloroplasts to ATP synthase
      subunits in bacteria. This review discusses the YidC/Alb3/Oxa1 protein family as
      well as their function in membrane insertion and two new structures of the
      bacterial YidC, which suggest a mechanism for membrane insertion by this family
      of insertases. 

PMID- 25947388
TI  - In situ electrochemical study of the interaction of cells with thermally treated
      titanium.
AB  - Micromotion and fretting wear between bone and Ti-based alloys in stem and dental
      implants breaks the passive film and exposes the metal to the action of the
      complex surrounding medium, generating substantial amounts of debris and
      continuous Ti ion release. In this work, oxidation treatments at low temperatures
      (277  degrees C, 5 h) have been used to promote the formation of wear-corrosion
      resistant titanium oxide on the Ti surface. The objective of this paper has been
      the study of the influence of live cells on the protectiveness of the oxide
      formed at these low temperatures. The interaction of cells with the modified
      surface has been studied by scanning electron microscopy, electrochemical
      impedance spectroscopy, polarization curves, and x-ray photoelectron spectroscopy
      (XPS). The chemical composition of the thermally treated Ti surface is mainly
      TiO2 as anatase-rich titanium dioxide with a low concentration of hydroxyl groups
      and a low mean nanoroughness that could promote good cell adhesion. The
      electrochemical results indicate that the cells alter the overall resistance of
      the thermally treated Ti surfaces by decreasing the oxide resistance with time.
      At the same time, the anodic current increases, which is associated with cathodic
      control, and is probably due to the difficulty of access of oxygen to the Ti
      substrate. XPS reveals the presence of proteins on the surface of the treated
      specimens in contact with the cells and a decrease in the Ti signal associated
      with the extracellular matrix on the surface and the reduction of the oxide
      thickness.

PMID- 25947389
TI  - Effects of air transient spark discharge and helium plasma jet on water,
      bacteria, cells, and biomolecules.
AB  - Atmospheric pressure DC-driven self-pulsing transient spark (TS) discharge
      operated in air and pulse-driven dielectric barrier discharge plasma jet (PJ)
      operated in helium in contact with water solutions were used for inducing
      chemical effects in water solutions, and the treatment of bacteria (Escherichia
      coli), mammalian cells (Vero line normal cells, HeLa line cancerous cells),
      deoxyribonucleic acid (dsDNA), and protein (bovine serum albumin). Two different
      methods of water solution supply were used in the TS: water electrode system and
      water spray system. The effects of both TS systems and the PJ were compared, as
      well as a direct exposure of the solution to the discharge with an indirect
      exposure to the discharge activated gas flow. The chemical analysis of water
      solutions was performed by using colorimetric methods of UV-VIS absorption
      spectrophotometry. The bactericidal effects of the discharges on bacteria were
      evaluated by standard microbiological plate count method. Viability, apoptosis
      and cell cycle were assessed in normal and cancerous cells. Viability of cells
      was evaluated by trypan blue exclusion test, apoptosis by Annexin V
      FITC/propidium iodide assay, and cell cycle progression by propidium iodide/RNase
      test. The effect of the discharges on deoxyribonucleic acid and protein were
      evaluated by fluorescence and UV absorption spectroscopy. The results of
      bacterial and mammalian cell viability, apoptosis, and cell cycle clearly show
      that cold plasma can inactivate bacteria and selectively target cancerous cells,
      which is very important for possible future development of new plasma therapeutic
      strategies in biomedicine. The authors found that all investigated bio-effects
      were stronger with the air TS discharge than with the He PJ, even in indirect
      exposure.

PMID- 25947390
TI  - Unraveling the interactions between cold atmospheric plasma and skin-components
      with vibrational microspectroscopy.
AB  - Using infrared and Raman microspectroscopy, the authors examined the interaction
      of cold atmospheric plasma with the skin's built-in protective cushion, the
      outermost skin layer stratum corneum. Following a spectroscopic analysis, the
      authors could identify four prominent chemical alterations caused by plasma
      treatment: (1) oxidation of disulfide bonds in keratin leading to a generation of
      cysteic acid; (2) formation of organic nitrates as well as (3) of new carbonyl
      groups like ketones, aldehydes and acids; and (4) reduction of double bonds in
      the lipid matter lanolin, which resembles human sebum. The authors suggest that
      these generated acidic and NO-containing functional groups are the source of an
      antibacterial and regenerative environment at the treatment location of the
      stratum corneum. Based upon the author's results, the authors propose a
      mechanistic view of how cold atmospheric plasmas could modulate the skin
      chemistry to produce positive long-term effects on wound healing: briefly, cold
      atmospheric plasmas have the potential to transform the skin itself into a
      therapeutic resource.

PMID- 25947391
TI  - Novel method to improve transdermal drug delivery by atmospheric microplasma
      irradiation.
AB  - Application of atmospheric plasma could be used for wound healing, skin
      rejuvenation, and wrinkle treatment. The authors explored the feasibility of
      atmospheric microplasma irradiation (AMI) for enhancement of percutaneous
      absorption of drugs as an alternative to hypodermic needles. Pig skin was used as
      a biological sample exposed to AMI and analyzed by attenuated total reflection
      Fourier transform infrared spectroscopy. A tape-stripping test (an evaluation
      method for skin-barrier performance) was also conducted to compare with AMI.
      Transepidermal water loss was also measured and compared with and without AMI.
      Results showed that surface modification of the stratum corneum (outermost skin
      layer) was observed upon AMI. Small pores on sample skin were observed with
      plasma jet irradiation due to the collision of charged particles. Percutaneous
      absorption was confirmed without damage upon microplasma irradiation. Our data
      suggested that dye pathways through skin samples could be related to the dynamic
      behavior of intercellular lipid bilayers, suggesting that AMI could enhance
      percutaneous absorption.

PMID- 25947392
TI  - Identification of the biologically active liquid chemistry induced by a
      nonthermal atmospheric pressure plasma jet.
AB  - The mechanism of interaction of cold nonequilibrium plasma jets with mammalian
      cells in physiologic liquid is reported. The major biological active species
      produced by an argon RF plasma jet responsible for cell viability reduction are
      analyzed by experimental results obtained through physical, biological, and
      chemical diagnostics. This is complemented with chemical kinetics modeling of the
      plasma source to assess the dominant reactive gas phase species. Different plasma
      chemistries are obtained by changing the feed gas composition of the cold argon
      based RF plasma jet from argon, humidified argon (0.27%), to argon/oxygen (1%)
      and argon/air (1%) at constant power. A minimal consensus physiologic liquid was
      used, providing isotonic and isohydric conditions and nutrients but is devoid of
      scavengers or serum constituents. While argon and humidified argon plasma led to
      the creation of hydrogen peroxide dominated action on the mammalian cells, argon
      oxygen and argon-air plasma created a very different biological action and was
      characterized by trace amounts of hydrogen peroxide only. In particular, for the
      argon-oxygen (1%), the authors observed a strong negative effect on mammalian
      cell proliferation and metabolism. This effect was distance dependent and showed
      a half life time of 30 min in a scavenger free physiologic buffer. Neither
      catalase and mannitol nor superoxide dismutase could rescue the cell
      proliferation rate. The strong distance dependency of the effect as well as the
      low water solubility rules out a major role for ozone and singlet oxygen but
      suggests a dominant role of atomic oxygen. Experimental results suggest that O
      reacts with chloride, yielding Cl2(-) or ClO(-). These chlorine species have a
      limited lifetime under physiologic conditions and therefore show a strong time
      dependent biological activity. The outcomes are compared with an argon MHz plasma
      jet (kinpen) to assess the differences between these (at least seemingly) similar
      plasma sources.

PMID- 25947393
TI  - Obstetrical disease spectrum in China: an epidemiological study of 111,767 cases
      in 2011.
AB  - BACKGROUND: No national research on maternal and fetal complications and outcomes
      has been carried out in the mainland of China in recent years. This study was to
      provide a scientific basis for better control of obstetrical and neonatal
      diseases and better allocation of medical resources by analyzing the
      epidemiological characteristics of obstetrical diseases in the mainland of China.
      METHODS: Hospitalized obstetrical cases from 19 tertiary and 20 secondary
      hospitals in 14 provinces (nationally representative) during the period January
      1, 2011 to December 31, 2011 were randomly selected. The general condition,
      pregnancy complications, and perinatal outcomes of the patients were studied.
      RESULTS: The top five medical and surgical complications of pregnant women in the
      mainland of China were anemia (6.34%), uterine fibroids (2.69%), thyroid disease
      (1.11%), thrombocytopenia (0.59%), and heart disease (0.59%). The incidences of
      premature rupture of membranes (PROM), preterm birth, prolonged pregnancy,
      hypertensive disorders complicating pregnancy (HDCP), multiple pregnancy,
      intrahepatic cholestasis of pregnancy (ICP), placenta previa, placental
      abruption, postpartum hemorrhage, and amniotic fluid embolism were 15.27%, 7.04%,
      6.71%, 5.35%, 1.57%, 1.22%, 1.14%, 0.54%, 3.26% and 0.06%, respectively. The
      incidences of anemia and prolonged pregnancy were significantly lower in tertiary
      than secondary hospitals (P < 0.001), whereas the incidence of uterine fibroids,
      thyroid diseases, thrombocytopenia, heart disease, PROM, preterm birth, HDCP,
      multiple pregnancy, ICP, placenta previa, and placental abruption were
      significantly higher in tertiary than secondary hospitals (P < 0.001). The
      cesarean section (CS) rate was 54.77%. The newborn sex ratio was 119:100, and
      1.03% of the neonates were malformed. The percentages of low birth weight and
      fetal macrosomia in full-term babies were 2.10% and 7.09%, respectively.
      CONCLUSIONS: The incidence of some obstetrical diseases is still high in the
      mainland of China. The CS rate is much higher than World Health Organization
      recommendations, in which CS delivery by maternal request (CDMR) accounted for a
      large proportion. The government should propose solutions to reduce CS rate,
      especially the rate of CDMR. Most obstetrical complications have higher incidence
      in tertiary hospitals compared with secondary hospitals. It is important to
      manage the health of pregnant women systematically, especially those with high
      risk factors.

PMID- 25947394
TI  - Effect of Intravenous Administration of Liposomal Prostaglandin E1 on
      Microcirculation in Patients with ST Elevation Myocardial Infarction Undergoing
      Primary Percutaneous Intervention.
AB  - BACKGROUND: Several studies have demonstrated that primary percutaneous coronary
      intervention (PCI) can result in reperfusion injury. This study aims to
      investigate the effectiveness of liposomal prostaglandin E1 (Lipo-PGE1,
      Alprostadil, Beijing Tide Pharmaceutical Co., Ltd.) for enhancing
      microcirculation in reperfusion injury. In addition, this study determined the
      optimal administration method for acute ST elevation myocardial infarction
      (STEMI) patients undergoing primary PCI. METHODS: Totally, 68 patients with STEMI
      were randomly assigned to two groups: intravenous administration of Lipo-PGE1
      (Group A), and no Lipo-PGE1 administration (Group B). The corrected thrombolysis
      in myocardial infarction (TIMI) frame count (cTFC) and myocardial blush grade
      (MBG) were calculated. Patients were followed up for 6 months. Major adverse
      cardiac events (MACE) were also measured. RESULTS: There was no significant
      difference in the baseline characteristics between the two groups. The cTFC
      parameter in Group A was significantly lower than Group B (18.06 +/- 2.06 vs.
      25.31 +/- 2.59, P < 0.01). The ratio of final MBG grade-3 was significantly
      higher (P < 0.05) in Group A (87.9%) relative to Group B (65.7%). There was no
      significant difference between the two groups in final TIMI-3 flow and no-reflow.
      Patients were followed up for 6 months, and the occurrence of MACE in Group A was
      significantly lower than that in Group B (6.1% vs. 25.9% respectively, P < 0.05).
      CONCLUSIONS: Myocardial microcirculation of reperfusion injury in patients with
      STEMI, after primary PCI, can be improved by administering Lipo-PGE1.

PMID- 25947395
TI  - Optimized Fluoroscopy Setting and Appropriate Project Position Can Reduce X-ray
      Radiation Doses Rates during Electrophysiology Procedures.
AB  - BACKGROUND: Nonfluoroscopic three-dimensional electroanatomical system is widely
      used nowadays, but X-ray remains indispensable for complex electrophysiology
      procedures. This study aimed to evaluate the value of optimized parameter setting
      and different projection position to reduce X-ray radiation dose rates. METHODS:
      From June 2013 to October 2013, 105 consecutive patients who underwent complex
      ablation were enrolled in the study. After the ablation, the radiation dose rates
      were measured by two different settings (default setting and optimized setting)
      with three projection positions (posteroanterior [PA] projection; left anterior
      oblique [LAO] 30 degrees  projection; and LAO 45 degrees  projection). The
      parameter of preset voltage, pulse width, critical voltage, peak voltage, noise
      reduction, edge enhancement, pulse rate, and dose per frame was modified in the
      optimized setting. RESULTS: The optimized setting reduced radiation dose rates by
      87.5% (1.7 Gy/min vs. 13.6 Gy/min, P < 0.001) in PA, 87.3% (2.5 Gy/min vs. 19.7
      Gy/min, P < 0.001) in LAO 30 degrees , 85.9% (3.1 Gy/min vs. 22.1 Gy/min, P <
      0.001) in LAO 45 degrees . Increase the angle of projection position will
      increase the radiation dose rate. CONCLUSIONS: We can reduce X-ray radiation dose
      rates by adjusting the parameter setting of X-ray system. Avoiding oblique
      projection of large angle is another way to reduce X-ray radiation dose rates.

PMID- 25947396
TI  - Single-site Baseline and Short-term Outcomes of Clinical Characteristics and Life
      Quality Evaluation of Chinese Wet Age-related Macular Degeneration Patients in
      Routine Clinical Practice.
AB  - BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of
      irreversible vision loss among the older population. In China, treatment of age
      related ocular diseases is becoming a priority in eye care services. This study
      was to investigate the clinical characteristics and quality of life of Chinese
      patients with wet AMD and current treatment types, to evaluate short-term gains
      in different treatments, and to investigate associations between visual function
      and vision-related quality of life (VRQoL). METHODS: A prospective,
      observational, noninterventional study was conducted. Basic data were collected
      from patients with clinical diagnoses of wet AMD before clinical assessments at
      baseline. VRQoL was measured with the Chinese version of the National Eye
      Institute Visual Function Questionnaire-25 (NEI VFQ-25). Correlations of the NEI
      VFQ-25 subscale scores with best-corrected visual acuity (BCVA) and between-group
      differences were analyzed. RESULTS: A total of 80 wet AMD patients were enrolled,
      with the mean age of 68.40 years. About one-quarter of wet AMD patients received
      intravitreal (IVT) ranibizumab treatment, and 67% of them were treated on a pro
      re nata basis. The visual acuity of patients treated with IVT ranibizumab at
      month 3 after treatment was significantly increased, whereas patients treated
      with traditional Chinese medicine achieved no significant improvement. Cronbach's
      alpha for the NEI VFQ-25 subscales ranged from 0.697 to 0.843. Eight subscale and
      overall composite scores were moderately correlated with the BCVA of the better
      seeing eye. Significant differences in the overall NEI VFQ-25 scores and other
      subscales were observed between patients with BCVA in the better-seeing eye of
      less than 50 letters and the others. CONCLUSIONS: Patients treated with IVT
      ranibizumab experienced better vision improvement at short-term follow-up. The
      Chinese version of the NEI VFQ-25 is a valid and reliable tool for assessing the
      VRQoL of Chinese wet AMD patients.

PMID- 25947397
TI  - A Pharmacokinetic and Pharmacodynamic Study on Intravenous Cefazedone Sodium in
      Patients with Community-acquired Pneumonia.
AB  - BACKGROUND: As a time-dependent antibiotic, the time of cefazedone concentration
      exceeds the minimum inhibitory concentration (MIC) is the key pharmacokinetic
      pharmacodynamic (PK-PD) variable associated with the killing of pathogens. The
      purpose of the study was to evaluate the clinical regimen rationality of
      intravenous cefazedone sodium in the treatment of community-acquired pneumonia
      (CAP) by PK/PD study. METHODS: Ten patients with mild to moderate CAP were
      enrolled to receive intravenous cefazedone sodium (2 g q12 h) for 7-14 days.
      Blood samples were collected in any day during day 5-7. Sputum specimens were
      collected before treatment for bacteria isolated, and susceptibility to
      cefazedone determined. PK-PD analysis was performed using the noncompartmental
      analysis of Phoenix WinNolin software (version 6.1, Pharsight Corporation, CA,
      USA). The maximal time above MIC (fT > MIC) was calculated, and its correlation
      with clinical efficacy was analyzed. RESULTS: All 10 patients completed the study
      and 8 of them were cured. Six strains were isolated from patients before
      treatment (one for each patient) and all susceptible to cefazedone. Five patients
      of six in culture positive group were cured. All pathogens were cleared at the
      end of therapy. The MICs were between 0.25 and 1 mg/L. The main PK parameters
      were C max 175.22 +/- 36.28 mg/L; T1/2 1.52 +/- 0.23 h; AUC (0-infinity) 280.51
      +/- 68.17 mg.L -1.h -1 ; CL 7.37 +/- 1.84 L/h; Vd 16.06 +/- 4.42 L. The average
      fT > MIC was 55.45 +/- 8.12%. CONCLUSIONS: Intravenous injection of cefazodone
      sodium with 2 g q12 h dosage regimen is used in the treatment of CAP caused by
      sensitive bacteria, either fT > MIC or clinical efficacy shows that such dosing
      regimen is reasonable.

PMID- 25947398
TI  - Preliminary study on the lesion location and prognosis of cubital tunnel syndrome
      by motor nerve conduction studies.
AB  - BACKGROUND: To study lesions' location and prognosis of cubital tunnel syndrome
      (CubTS) by routine motor nerve conduction studies (MNCSs) and short-segment nerve
      conduction studies (SSNCSs, inching test). METHODS: Thirty healthy subjects were
      included and 60 ulnar nerves were studied by inching studies for normal values.
      Sixty-six patients who diagnosed CubTS clinically were performed bilaterally by
      routine MNCSs and SSNCSs. Follow-up for 1-year, the information of brief
      complaints, clinical symptoms, and physical examination were collected. RESULTS:
      Sixty-six patients were included, 88 of nerves was abnormal by MNCS, while 105
      was abnormal by the inching studies. Medial epicondyle to 2 cm above medial
      epicondyle is the most common segment to be detected abnormally (59.09%), P <
      0.01. Twenty-two patients were followed-up, 17 patients' symptoms were improved.
      Most of the patients were treated with drugs and modification of bad habits.
      CONCLUSIONS: (1) SSNCSs can detect lesions of compressive neuropathy in CubTS
      more precisely than the routine motor conduction studies. (2) SSNCSs can diagnose
      CubTS more sensitively than routine motor conduction studies. (3) In this study,
      we found that medial epicondyle to 2 cm above the medial epicondyle is the most
      vulnerable place that the ulnar nerve compressed. (4) The patients had a better
      prognosis who were abnormal in motor nerve conduction time only, but not
      amplitude in compressed lesions than those who were abnormal both in velocity and
      amplitude. Our study suggests that SSNCSs is a practical method in detecting
      ulnar nerve compressed neuropathy, and sensitive in diagnosing CubTS. The
      compound muscle action potentials by SSNCSs may predict prognosis of CubTS.

PMID- 25947399
TI  - Changes in the Vision-related Resting-state Network in Pituitary Adenoma Patients
      After Vision Improvement.
AB  - BACKGROUND: The aim of this research was to investigate the changes in the vision
      related resting-state network (V-RSN) in pituitary adenoma (PA) patients after
      vision improvement, which was induced by operative treatment. METHODS: Ten PA
      patients with an improved visual acuity or/and visual field after transsphenoidal
      pituitary tumor resection were recruited and underwent a complete neuro
      ophthalmologic evaluation, as well as an magnetic resonance imaging (MRI)
      protocol, including structural and resting-state functional MRI sequences before
      and after the operation. The regional homogeneity (ReHo) of the V-RSN was
      evaluated. Two sample t-test was performed to identify the significant
      differences in the V-RSN in the PA patients before and after transsphenoidal
      pituitary tumor resection. RESULTS: Compared with the preoperation counterparts,
      the PA patients with improved vision after the operation exhibited reduced ReHo
      in the bilateral thalamus, globus pallidus, caudate nucleus, putamen nucleus,
      supplementary motor area, and left hippocampal formation, and increased ReHo in
      the bilateral cuneus gyrus, calcarine gyrus, right lingual gyrus, and fusiform
      gyrus. CONCLUSIONS: PA patients with improved vision exhibit increased neural
      activity within the visual cortex, but decreased neural activity in subareas of
      the multisensory and multimodal systems beyond the vision cortex.

PMID- 25947400
TI  - Clinicopathological characteristics and prognostic factors of intrahepatic
      biliary cystadenocarcinoma.
AB  - BACKGROUND: Surgical resection is generally considered the main curative
      treatment for intrahepatic biliary cystadenocarcinoma (IBCA) or suspected IBCAs,
      but controversy exists regarding the prognosis for IBCAs. This study aimed to
      describe the clinicopathological characteristics of IBCA and identify prognostic
      factors that may influence the survival of patients treated with surgical
      procedures. METHODS: Thirty-four patients with histologically confirmed IBCA
      treated between January 2000 and June 2014 were included. The clinical
      characteristics of patients with IBCA were compared with those of 41 patients
      with intrahepatic biliary cystadenoma (IBC); factors that significant difference
      were analyzed for prognosis analysis of IBCA using multivariate/univariate Cox
      proportional hazards regression models. Survival curves were constructed using
      the Kaplan-Meier method and compared using the log-rank test. RESULTS: IBCAs had
      a strong female predominance, and the most common presenting symptoms were
      abdominal pain or discomfort. Compared with IBCs, IBCAs occurred in older
      patients, in more male patients, and were associated statistically significant
      abnormal increase in alanine aminotransferase (P = 0.01) and total bilirubin (P =
      0.04). Mural nodules were more frequently seen with IBCAs and may associate with
      malignancy. It was difficult to differentiate between IBC and IBCA based on
      laboratory examination and imaging findings. Although complete resection is
      recommended, enucleation with negative margins also achieved good outcomes.
      Median overall patient survival was 76.2 months; survival at 1, 3, and 5 years
      was 88.0%, 68.7%, and 45.8%, respectively. Radical resection and noninvasive
      tumor type were independent prognostic factors for overall survival. CONCLUSIONS:
      It remains difficult to distinguish between cystadenomas and cystadenocarcinomas
      based on laboratory examination and image findings. Complete resection is
      recommended for curative treatment, and patients should be closely followed
      postoperatively, particularly those with invasive tumors.

PMID- 25947401
TI  - Diagnostic Value of Prospective Electrocardiogram-triggered Dual-source Computed
      Tomography Angiography for Infants and Children with Interrupted Aortic Arch.
AB  - BACKGROUND: Accurate assessment of intra- as well as extra-cardiac malformations
      and radiation dosage concerns are especially crucial to infants and children with
      interrupted aortic arch (IAA). The purpose of this study is to investigate the
      value of prospective electrocardiogram (ECG)-triggered dual-source computed
      tomography (DSCT) angiography with low-dosage techniques in the diagnosis of IAA.
      METHODS: Thirteen patients with suspected IAA underwent prospective ECG-triggered
      DSCT scan and transthoracic echocardiography (TTE). Surgery was performed on all
      the patients. A five-point scale was used to assess image quality. The diagnostic
      accuracy of DSCT angiography and TTE was compared with the surgical findings as
      the reference standard. A nonparametric Chi-square test was used for comparative
      analysis. P <0.05 was considered as a significant difference. The mean effective
      radiation dose (ED) was calculated. RESULTS: Diagnostic DSCT images were obtained
      for all the patients. Thirteen IAA cases with 60 separate cardiovascular
      anomalies were confirmed by surgical findings. The diagnostic accuracy of TTE and
      DSCT for total cardiovascular malformations was 93.7% and 97.9% (P > 0.05), and
      that for extra-cardiac vascular malformations was 92.3% and 99.0% (P < 0.05),
      respectively. The mean score of image quality was 3.77 +/- 0.83. The mean ED was
      0.30 +/- 0.04 mSv (range from 0.23 mSv to 0.39 mSv). CONCLUSIONS: In infants and
      children with IAA, prospective ECG-triggered DSCT with low radiation exposure and
      high diagnostic efficiency has higher accuracy compared to TTE in detection of
      extra-cardiac vascular anomalies.

PMID- 25947402
TI  - Behavioral effects of deep brain stimulation of the anterior nucleus of thalamus,
      entorhinal cortex and fornix in a rat model of Alzheimer's disease.
AB  - BACKGROUND: Recent clinical and preclinical studies have suggested that deep
      brain stimulation (DBS) can be used as a tool to enhance cognitive functions. The
      aim of the present study was to investigate the impact of DBS at three separate
      targets in the Papez circuit, including the anterior nucleus of thalamus (ANT),
      the entorhinal cortex (EC), and the fornix (FX), on cognitive behaviors in an
      Alzheimer's disease (AD) rat model. METHODS: Forty-eight rats were subjected to
      an intrahippocampal injection of amyloid peptides 1-42 to induce an AD model.
      Rats were divided into six groups: DBS and sham DBS groups of ANT, EC, and FX.
      Spatial learning and memory were assessed by the Morris water maze (MWM).
      Recognition memory was investigated by the novel object recognition memory test
      (NORM). Locomotor and anxiety-related behaviors were detected by the open field
      test (OF). By using two-way analysis of variance (ANOVA), behavior differences
      between the six groups were analyzed. RESULTS: In the MWM, the ANT, EC, and FX
      DBS groups performed differently in terms of the time spent in the platform zone
      (F(2,23) = 6.04, P < 0.01), the frequency of platform crossing (F(2,23) = 11.53,
      P < 0.001), and the percent time spent within the platform quadrant (F(2,23) =
      6.29, P < 0.01). In the NORM, the EC and FX DBS groups spent more time with the
      novel object, although the ANT DBS group did not (F(2,23) = 10.03, P < 0.001). In
      the OF, all of the groups showed a similar total distance moved (F (1,42) = 1.14,
      P = 0.29) and relative time spent in the center (F(2,42) = 0.56, P = 0.58).
      CONCLUSIONS: Our results demonstrated that DBS of the EC and FX facilitated
      hippocampus-dependent spatial memory more prominently than ANT DBS. In addition,
      hippocampus-independent recognition memory was enhanced by EC and FX DBS. None of
      the targets showed side-effects of anxiety or locomotor behaviors.

PMID- 25947403
TI  - Conditional Knockout of Src Homology 2 Domain-containing Protein Tyrosine
      Phosphatase-2 in Myeloid Cells Attenuates Renal Fibrosis after Unilateral Ureter
      Obstruction.
AB  - BACKGROUND: Src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP
      2) is a kind of intracellular protein tyrosine phosphatase. Studies have revealed
      its roles in various disease, however, whether SHP-2 involves in renal fibrosis
      remains unclear. The aim of this study was to explore the roles of myeloid cells
      SHP-2 in renal interstitial fibrosis. METHODS: Myeloid cells SHP-2 gene was
      conditionally knocked-out (CKO) in mice using loxP-Cre system, and renal
      interstitial fibrosis was induced by unilateral ureter obstruction (UUO). The
      total collagen deposition in the renal interstitium was assessed using
      picrosirius red stain. F4/80 immunostaing was used to evaluate macrophage
      infiltration in renal tubular interstitium. Quantitative real-time polymerase
      chain reaction and enzyme linked immunosorbent assay were used to analyze the
      production of cytokines in the kidney. Transferase-mediated dUTP nick-end
      labeling stain was used to assess the apoptotic renal tubular epithelial cells.
      RESULTS: Src homology 2 domain-containing protein tyrosine phosphatase-2 gene CKO
      in myeloid cells significantly reduced collagen deposition in the renal
      interstitium after UUO. Macrophage infiltration was evidently decreased in renal
      tubular interstitium of SHP-2 CKO mice. Meanwhile, the production of pro
      inflammatory cytokines was significantly suppressed in SHP-2 CKO mice. However,
      no significant difference was observed in the number of apoptotic renal tubular
      epithelial cells between wild-type and SHP-2 CKO mice. CONCLUSIONS: Our
      observations suggested that SHP-2 in myeloid cells plays a pivotal role in the
      pathogenesis of renal fibrosis, and that silencing of SHP-2 gene in myeloid cells
      may protect renal from inflammatory damage and prevent renal fibrosis after renal
      injury.

PMID- 25947404
TI  - Inhibition of Nonsmall Cell Lung Cancer Cell Migration by Protein Arginine
      Methyltransferase 1-small Hairpin RNA Through Inhibiting Epithelial-mesenchymal
      Transition, Extracellular Matrix Degradation, and Src Phosphorylation In Vitro.
AB  - BACKGROUND: Protein arginine methyltransferases 1 (PRMT1) is over-expressed in a
      variety of cancers, including lung cancer, and is correlated with a poor
      prognosis of tumor development. This study aimed to investigate the role of PRMT1
      in nonsmall cell lung cancer (NSCLC) migration in vitro. METHODS: In this study,
      PRMT1 expression in the NSCLC cell line A549 was silenced using lentiviral vector
      mediated short hairpin RNAs. Cell migration was measured using both scratch wound
      healing and transwell cell migration assays. The mRNA expression levels of matrix
      metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 1, 2
      (TIMP1, 2) were measured using quantitative real-time reverse transcription
      polymerase chain reaction. The expression levels of protein markers for
      epithelial-mesenchymal transition (EMT) (E-cadherin, N-cadherin), focal adhesion
      kinase (FAK), Src, AKT, and their corresponding phosphorylated states were
      detected by Western blot. RESULTS: Cell migration was significantly inhibited in
      the PRMT1 silenced group compared to the control group. The mRNA expression of
      MMP-2 decreased while TIMP1 and TIMP2 increased significantly. E-cadherin mRNA
      expression also increased while N-cadherin decreased. Only phosphorylated Src
      levels decreased in the silenced group while FAK or AKT remained unchanged.
      CONCLUSIONS: PRMT1-small hairpin RNA inhibits the migration abilities of NSCLC
      A549 cells by inhibiting EMT, extracellular matrix degradation, and Src
      phosphorylation in vitro.

PMID- 25947405
TI  - MreBCD-associated Cytoskeleton is Required for Proper Segregation of the
      Chromosomal Terminus during the Division Cycle of Escherichia Coli.
AB  - BACKGROUND: In prokaryotic organisms, the mechanism responsible for the accurate
      partition of newly replicated chromosomes into daughter cells is incompletely
      understood. Segregation of the replication terminus of the circular prokaryotic
      chromosome poses special problems that have not previously been addressed. The
      aim of this study was to investigate the roles of several protein components
      (MreB, MreC, and MreD) of the prokaryotic cytoskeleton for the faithful
      transmission of the chromosomal terminus into daughter cells. METHODS: Strain LQ1
      (mreB::cat), LQ2 (mreC::cat), and LQ3 (mreD::cat) were constructed using the Red
      recombination system. LQ11/pLAU53, LQ12/pLAU53, LQ13/pLAU53, LQ14/pLAU53, and
      LQ15/pLAU53 strains were generated by P1transduction of (tetO) 240 -Gm and (lacO)
      240 -Km cassettes from strains IL2 and IL29. Fluorescence microscopy was
      performed to observe localization pattern of fluorescently-labeled origin and
      terminus foci in wild-type and mutant cells. SOS induction was monitored as gfp
      fluorescence from PsulA-gfp in log phase cells grown in Luria-Bertani medium at
      37 degrees C by measurement of emission at 525 nm with excitation at 470 nm in a
      microplate fluorescence reader. RESULTS: Mutational deletion of the mreB, mreC,
      or mreD genes was associated with selective loss of the terminus region in
      approximately 40% of the cells within growing cultures. This was accompanied by
      significant induction of the SOS DNA damage response, suggesting that deletion of
      terminus sequences may have occurred by chromosomal cleavage, presumably caused
      by ingrowth of the division septum prior to segregation of the replicated
      terminal. CONCLUSIONS: These results imply a role for the MreBCD cytoskeleton in
      the resolution of the final products of terminus replication and/or in the
      specific movement of newly replicated termini away from midcell prior to
      completion of septal ingrowth. This would identify a previously unrecognized
      stage in the overall process of chromosome segregation.

PMID- 25947406
TI  - Efficacy and Safety of Lenalidomide in the Treatment of Multiple Myeloma: A
      Systematic Review and Meta-analysis of Randomized Controlled Trials.
AB  - BACKGROUND: Lenalidomide has emerged as an important treatment for patients with
      multiple myeloma (MM). However, its role in the management of MM is still
      controversial and requires further clarification. The aim of this study was to
      evaluate efficacy and safety of lenalidomide for MM using a meta-analysis.
      METHODS: We searched the electronic databases including: PubMed, EMBASE and the
      Cochrane Center Register of Controlled Trials. Seven randomized clinical trials
      were identified, which included a total of 2357 patients with MM who received
      lenalidomide-containing, noncontaining lenalidomide regimens or placebo as
      induction therapy or maintenance therapy. The outcomes included overall response
      (OR) rate, complete response (CR) rate, 3-year progression-free survival (PFS)
      rate, 3-year overall survival (OS) rate, and different types of treatment-related
      adverse events. We calculated the risk ratios (RRs) as well as their 95%
      confidence intervals of these outcomes and pooled the results using RevMan 5.2
      software. RESULTS: For patients with previously untreated MM, OR rate and CR rate
      was significantly higher in lenalidomide-containing group than the control group.
      For relapsed or refractory MM patients, lenalidomide-containing regimens
      significantly improved the OR rate, CR rate, 3-year PFS rate and 3-year OS rate.
      With regard to MM patients after autologous stem cell transplantation,
      lenalidomide maintenance therapy significantly improved 3-year PFS rate but did
      not result in improved 3-year OS rate. In terms of toxicities, lenalidomide
      therapy has a higher rate of Grade 3-4 grade cytopenias, infection, deep-vein
      thrombosis, and diarrhea. Furthermore, the incidence of second primary
      malignancies was significantly higher in the lenalidomide group. CONCLUSIONS: The
      lenalidomide-containing regimens as induction therapy clearly increased response
      rates and improved intervals of survival with acceptable toxicity rates for
      patients with MM. However, when physicians choose to use the lenalidomide as
      maintenance therapy, whether the benefits outweigh the risks should be taken into
      account.

PMID- 25947407
TI  - Ceramic on Ceramic or Ceramic-on-polyethylene for Total Hip Arthroplasty: A
      Systemic Review and Meta-analysis of Prospective Randomized Studies.
AB  - BACKGROUND: Wear debris of polyethylene has become a restraining factor of the
      durability for total hip arthroplasty (THA). Ceramic on ceramic (COC) has better
      wear resistance while the squeaking sound and prosthesis fracture are of concern.
      It is still a controversy that bearing couples are better for THA. METHODS: We
      performed a systematic review of all English articles identified from PubMed
      (1966-), Embase (1980-) and the Cochrane Library. Clinical outcomes,
      complications, revision rates, and radiographic outcomes of COC-THA and ceramic
      on polyethylene (COP)-THA were compared and evaluated. RESULTS: Eight prospective
      randomized trials enrolling a total of 1508 patients and 1702 THA surgeries were
      identified. Our results demonstrated the prosthesis fracture and the squeaking
      sound is significantly higher in COC group and higher wear rate of the COP. Hip
      function, loosening rate, dislocation rate, revision rate, and the osteolysis
      rate were comparable between two groups. According to Grading of Recommendations
      Assessment, Development and Evaluation system assessment, the strength of
      evidence was high for prosthesis fracture, dislocation, osteolysis, and moderate
      for radiolucent line or loosening, hip noise, and revision. CONCLUSIONS: Up to
      now, there is insufficient evidence to identify any clinical advantage of COC
      compared with COP. Longer follow-up of larger randomized trial is needed to
      clarify the outcomes.

PMID- 25947408
TI  - Natural history of small renal masses.
AB  - OBJECTIVE: To review the natural history and growth kinetics of small renal
      masses (SRMs). DATA SOURCES: The literature concerning natural history and growth
      kinetics of SRMs was collected from PubMed published from 1990 to 2014. STUDY
      SELECTION: We included all the relevant articles on the active surveillance (AS)
      or delayed treatment for SRMs in English, with no limitation of study design.
      RESULTS: SRMs under AS have a slow growth potential in general. The mean linear
      growth rate is 0.33 cm/year, the mean volumetric growth rate is 9.48 cm 3 /year.
      The rate of metastasis during AS is below 2%. Some factors are associated with
      the growth rate of SRMs, including tumor grade, histological subtype, initial
      tumor size, age, radiographic characteristics, and molecular markers. No definite
      predictor of growth rate of SRMs is defined at present. SRMs with high tumor
      grade and the subtype of clear cell renal cell carcinoma may have aggressive
      growth potential. CONCLUSIONS: AS is a reasonable choice for elderly patients
      with SRMs, who are at high risk from surgery. Progression during observation is
      the biggest concern while performing AS. There is no definite predictor of
      progression for SRMs under AS. Percutaneous renal biopsy providing
      immunohistological and genic biomarkers may improve the understanding of natural
      history of SRMs.

PMID- 25947409
TI  - Role of MicroRNAs in Malignant Glioma.
AB  - OBJECTIVE: This overview seeked to bring together the microRNA (miRNA) researches
      on biogenesis and bio-function in these areas of clinical diagnosis and therapy
      for malignant glioma. DATA SOURCES: Using the keyword terms "glioma" and "miRNA,"
      we performed the literature search in PubMed, Ovid, and web.metstr.com databases
      from their inception to October 2014. STUDY SELECTION: In screening out the
      quality of the articles, factors such as clinical setting of the study, the size
      of clinical samples were taken into consideration. Animal studied for
      verification and reviews article were also included in our data collection.
      RESULTS: Despite many advance in miRNA for malignant glioma, further studies were
      still required to focus on the following aspects: (i) Improving the understanding
      about biogenesis of miRNA and up-down regulation; (ii) utilizing high-throughput
      miRNA expression analysis to screen out the core miRNA for glioma; (iii) Focusing
      related miRNAs on the signal transduction pathways that regulate the
      proliferation and growth of glioma. CONCLUSIONS: We discussed the most promising
      miRNA, correlative signaling pathway and their relation with gliomas in the way
      of prompting miRNA target into being a clinical therapeutic strategy.

PMID- 25947410
TI  - A systemic review of autologous fat grafting survival rate and related severe
      complications.
AB  - OBJECTIVE: Clinical application of autologous fat grafting (AFG) is quickly
      expanding. Despite the widely acceptance, long-term survival rate (SR) of AFG
      remains a question not yet solved. Meanwhile, although rare, severe complications
      related to AFG including vision loss, stroke even death could be seen in the
      literature. DATA SOURCES: A comprehensive research of PubMed database to June
      2013 was performed according to guidelines of the American Society of Plastic
      Surgeons Fat Graft Task Force Assessment Methodology. Articles were screened
      using predetermined inclusion and exclusion criteria. STUDY SELECTION: Data
      collected included patient characteristics, surgical technique, donor site,
      recipient site, graft amount, and quantified measurement methods. Patient cohorts
      were pooled, and SR was calculated. All the severe complications were also
      summarized according to the different clinical characteristics. RESULTS: Of 550
      articles, 16 clinical articles and 10 animal studies met the inclusion criteria
      and provided quantified measurement methods. Totally, 596 patients were included.
      SR varied from 34% to 82% in breast and 30-83% in the facial area. Nude mice were
      applied to investigate human fat grafting SR (38.3-52.5% after 15 weeks). Rabbits
      were commonly used to study animal AFG SR (14.00-14.56% after 1-year). Totally,
      21 severe complications were reported, including death (2), stroke (10), vision
      loss (11, 8 of which accompanied with stroke), sepsis (3), multiple abscess (1)
      and giant fat necrotic cyst (2). Ten of these complications happened within 10
      years. CONCLUSIONS: There is no unified measurement method to evaluate fat graft
      SR until now and no clinical evidence to show better SR according to different
      donor and recipient cite. Body mass index change between pre- and postoperation
      may be the bias factor in evaluating fat SR. Fat embolisms of the ophthalmic
      artery and the middle cerebral artery are the most severe complication of AFG and
      still lack of effective treatment.

PMID- 25947412
TI  - Current clinical research of acute kidney injury in China.

PMID- 25947411
TI  - The experts consensus for patient management of neurosurgical critical care unit
      in China (2015).

PMID- 25947413
TI  - Traumatic diaphragmatic hernia associated with pelvic ring fracture.

PMID- 25947414
TI  - Frequency-specific Alterations of Large-scale Functional Brain Networks in
      Patients with Alzheimer's Disease: Erratum.

PMID- 25947415
TI  - First-in-man Implantation of the XINSORB Bioresorbable Sirolimus-eluting Scaffold
      in China.

PMID- 25947416
TI  - Micro-transesophageal Echocardiography Guided Mitral Valve Repair After Balloon
      Dilation for Aortic Valve Stenosis in a Small Infant.

PMID- 25947417
TI  - Rapid regression of Kaposi's sarcoma of the hard palate under therapy with
      boosted elvitegravir-containing fixdose antiretroviral combination therapy.
AB  - INTRODUCTION: Kaposi's sarcoma (KS) is a rare vascular tumor that may occur in a
      severe, rapidly progressive form, namely in HIV/AIDS patients. HIV-associated KS
      mainly affects the skin and mucous membranes. CASE PRESENTATION: We report about
      an HIV-positive patient who presented with an exophytic growing tumor in the
      region of the hard palate and severe problems regarding his dental status.
      Histological examination revealed evidence of AIDS-related KS. Antiretroviral
      therapy initiation with
      elvitegravir/cobicistat/emtricitabine(FTC)/tenofovirdisoproxilfumarat (E/c/F/T
      fix dose combination) resulted in rapid complete remission of the KS within 2
      months. CONCLUSION: In this case of a treatment-naive HIV-infected patient with
      coexisting KS, antiretroviral therapy with E/c/FTC/TDF was very well suited to
      achieve rapid complete remission of KS.

PMID- 25947418
TI  - Dopaminergic Differentiation of Human Embryonic Stem Cells on PA6-Derived
      Adipocytes.
AB  - Human embryonic stem cells (hESCs) are a promising source for cell replacement
      therapies. Parkinson's disease is one of the candidate diseases for the cell
      replacement therapy since the motor manifestations of the disease are associated
      with the loss of dopaminergic neurons in the substantia nigra pars compacta.
      Stromal cell-derived inducing activity (SDIA) is the most commonly used method
      for the dopaminergic differentiation of hESCs. This chapter describes a simple,
      reliable, and scalable dopaminergic induction method of hESCs using PA6-derived
      adipocytes. Coculturing hESCs with PA6-derived adipocytes markedly reduces the
      variable outcomes among experiments. Moreover, the colony differentiation step of
      this method can also be used for the dopaminergic induction of mouse embryonic
      stem cells and NTERA2 cells as well. 

PMID- 25947419
TI  - A systematic study on Endotribelos Grodhaus (Diptera: Chironomidae) from Brazil
      including DNA barcoding to link males and females.
AB  - Six new species of Endotribelos from Brazil are described and illustrated as
      male, female, pupa and larva: E. bicolor sp. n., E. fulvidus sp. n., E. jaragua
      sp. n., E. jiboia sp. n., E. semibruneus sp. n. and E. sublettei sp. n. The
      female of E. calophylli Roque & Trivinho-Strixino and the larvae of four unknown
      morphotypes are also described. Keys including males and larvae of all known
      species of Endotribelos are provided. Adults' males and females from five species
      were linked using DNA Barcoding mtCOI sequences. 

PMID- 25947420
TI  - Type specimens in the Port Elizabeth Museum, South Africa, including the
      historically important Albany Museum collection. Part 1: Amphibians.
AB  - The Port Elizabeth Museum houses the consolidated herpetological collections of
      three provincial museums of the Eastern Cape, South Africa: the Port Elizabeth
      Museum (Port Elizabeth), the Amatole (previously Kaffarian) Museum (King Williams
      Town), and the Albany Museum (Grahamstown). Under John Hewitt, Albany Museum was
      the main centre of herpetological research in South Africa from 1910-1940, and he
      described numerous new species, many based on material in the museum collection.
      The types and other material from the Albany Museum are now incorporated into the
      Port Elizabeth Museum Herpetology collection (PEM). Due to the vague typification
      of much of Hewitt's material, the loss of the original catalogues in a fire and
      the subsequent deterioration of specimen labels, the identification of this type
      material is often troublesome. Significant herpetological research has been
      undertaken at the PEM in the last 35 years, and the collection has grown to be
      the third largest in Africa. During this period, numerous additional types have
      been deposited in the PEM collection, generated by active taxonomic research in
      the museum. As a consequence, 43 different amphibian taxa are represented by 37
      primary and 151 secondary type specimens in the collection. This catalogue
      provides the first documentation of these types. It provides the original name,
      the original publication date, journal number and pagination, reference to
      illustrations, current name, museum collection number, type locality, notes on
      the type status, and photographs of all holotypes and lectotypes. Where necessary
      to maintain nomenclatural stability, and where confused type series are housed in
      the PEM collection, lectotypes and paralectotypes are nominated. 

PMID- 25947421
TI  - Palaearctic Hoplitis bees of the subgenus Platosmia (Megachilidae, Osmiini):
      biology, taxonomy and key to species.
AB  - Platosmia, a subgenus of the osmiine bee genus Hoplitis (Megachilidae), contains
      ten species, which are confined to desertic and semidesertic areas of the
      Palaearctic region. Analysis of female pollen loads and field observations
      indicate that several H. (Platosmia) species are strictly oligolectic on Reseda
      (Resedaceae) and possibly Hedysareae (Fabaceae), while others are mesolectic on
      both Reseda and Fabaceae. The few data available so far suggest that preexisting
      cavities in stones and rocks serve as nesting sites of H. (Platosmia). The
      taxonomic revision of H. (Platosmia) revealed the existence of an undescribed
      species from the Arabian peninsula, H. arabiae spec. nov.. Hoplitis incognita
      Zanden, 1996 and H. quarzazati (Zanden, 1998) are newly synonymized with H.
      maghrebensis (Zanden, 1992) and H. platalea (Warncke, 1990), respectively.
      Identification keys for all H. (Platosmia) species are given including the
      hitherto unknown male or female sex of three species. 

PMID- 25947422
TI  - Two new species of Lysianassidae Dana, 1849 from Australia: Riwo zeidleri and
      Socarnella delectabilis (Crustacea: Peracarida: Amphipoda).
AB  - The new species Riwo zeidleri and Socarnella delectabilis are described. Prior to
      this study Riwo Lowry & Stoddart, 1995 was a monotypic genus, while Socarnella
      Walker, 1904 consisted of only two described species. The distribution of Riwo is
      expanded southwards from northern Papua New Guinea and the Great Barrier Reef to
      the south coast of Australia and the distribution of Socarnella is expanded
      further southward from Sri Lanka and the South China Sea, to the west coast of
      Australia. 

PMID- 25947423
TI  - DNA barcoding of Neotropical black flies (Diptera: Simuliidae): Species
      identification and discovery of cryptic diversity in Mesoamerica.
AB  - Although correct taxonomy is paramount for disease control programs and
      epidemiological studies, morphology-based taxonomy of black flies is extremely
      difficult. In the present study, the utility of a partial sequence of the COI
      gene, the DNA barcoding region, for the identification of species of black flies
      from Mesoamerica was assessed. A total of 32 morphospecies were analyzed, one
      belonging to the genus Gigantodax and 31 species to the genus Simulium and six of
      its subgenera (Aspathia, Eusimulium, Notolepria, Psaroniocompsa, Psilopelmia,
      Trichodagmia). The Neighbour Joining tree (NJ) derived from the DNA barcodes
      grouped most specimens according to species or species groups recognized by
      morphotaxonomic studies. Intraspecific sequence divergences within
      morphologically distinct species ranged from 0.07% to 1.65%, while higher
      divergences (2.05%-6.13%) in species complexes suggested the presence of cryptic
      diversity. The existence of well-defined groups within S. callidum (Dyar &
      Shannon), S. quadrivittatum Loew, and S. samboni Jennings revealed the likely
      inclusion of cryptic species within these taxa. In addition, the suspected
      presence of sibling species within S. paynei Vargas and S. tarsatum Macquart was
      supported. DNA barcodes also showed that specimens of species that are difficult
      to delimit morphologically such as S. callidum, S. pseudocallidum Diaz Najera, S.
      travisi Vargas, Vargas & Ramirez-Perez, relatives of the species complexes such
      as S. metallicum Bellardi s.l. (e.g., S. horacioi Okazawa & Onishi, S. jobbinsi
      Vargas, Martinez Palacios, Diaz Najera, and S. puigi Vargas, Martinez Palacios &
      Diaz Najera), and S. virgatum Coquillett complex (e.g., S. paynei and S.
      tarsatum) grouped together in the NJ analysis, suggesting they represent valid
      species. DNA barcoding combined with a sound morphotaxonomic framework provided
      an effective approach for the identification of medically important black flies
      species in Mesoamerica and for the discovery of hidden diversity within this
      group. 

PMID- 25947424
TI  - New species and new records of Xenelmis Hinton (Coleoptera: Elmidae) from
      Southeastern Brazil.
AB  - The genus Xenelmis is found in the Nearctic and Neotropical regions. Currently,
      seven out of thirteen species are registered from Brazil. Here, two new species
      of Xenelmis from Brazil are described and illustraded-Xenelmis sinecarina sp.
      nov. and Xenelmis granatoides sp. nov. Additionaly, X. granata and X. micros are
      characterized and illustrated.

PMID- 25947425
TI  - A new species of Compsoneuriella Ulmer, 1939 (Ephemeroptera: Heptageniidae) from
      Thailand.
AB  - A new species of Compsoneuriella Ulmer, 1939 is described based on male and
      female imagos, nymphs and eggs from Ratchaburi province, western Thailand.
      Compsoneuriella braaschi sp. nov. is closely related to C. thienemanni Ulmer,
      1939, from Java and Sumatra, but differs in the larval stage by the maxilla
      bearing only 8-9 comb-shaped setae on the crown, two strong medial setae on the
      glossa, gills V-VII apically acutely pointed and the posterior margin of the
      abdominal terga without distinct rows of submarginal microdenticles. In the male
      imaginal stage, the new species differs from C. thienemanni by having more
      reduced spines on the penis lobes and the titillators being directed outwards and
      strongly pointed at their apices. 

PMID- 25947426
TI  - A new species of the "mexicanus" group of the genus Vaejovis C. L. Koch, 1836
      from the Mexican state of Aguascalientes (Scorpiones: Vaejovidae).
AB  - A new species of Vaejovis is described from the Mexican state of Aguascalientes.
      It is assigned to the "mexicanus" group and compared with similar species from
      Jalisco, Guanajuato, and San Luis Potosi. A map with their known distributions is
      provided. 

PMID- 25947428
TI  - Fried spicy Linnaeus--the consequences of indiscriminate citation of authors of
      scientific names.

PMID- 25947427
TI  - Description of a new tracheline spider, Trachelas mombachensis sp. n., in the T.
      bispinosus species group from the Mombacho Volcano in Nicaragua (Araneae:
      Trachelidae).

PMID- 25947429
TI  - The assassin bug subfamily Tribelocephalinae (Hemiptera: Heteroptera: Reduviidae)
      from Japan, with descriptions of eight new species in the genera Opistoplatys and
      Abelocephala.
AB  - We examined the Japanese species of the reduviid subfamily Tribelocephalinae. We
      identified two species of Opistoplatys Westwood, which is the genus with the
      second largest number of species, and six species of Abelocephala Maldonado,
      which to date has been referred to as a monotypic genus. All the identified
      species represent new species and they are described herein under the following
      names: Opistoplatys minimus sp. nov., Opistoplatys flavolineatus sp. nov.,
      Abelocephala albula sp. nov., Abelocephala araiorum sp. nov., Abelocephala
      nakatai sp. nov., Abelocephala yaeyamensis sp. nov., Abelocephala major sp. nov.,
      and Abelocephala longiceps sp. nov. Species of Abelocephala can be distinguished
      from each other based on multiple morphological characters such as body length,
      ratio of the length to the width of the head, color of the posterior pronotal
      lobe, shading and pattern of color in the hemelytral basal part, and acuteness or
      roundness in the apical angle of the outer (larger) cell on the hemelytral
      membranes. We confirmed that the Japanese tribelocephalines are ground
      inhabitants living under and within the forest leaf litter. Our results inferred
      that species of Opistoplatys have positive phototaxis but generally move by
      walking, whereas species of Abelocephala have negative phototaxis but frequently
      fly above the forest floor. 

PMID- 25947430
TI  - List of the type-specimens of Reduviidae (Hemiptera: Heteroptera) in the
      Triatomines Collection of the Oswaldo Cruz Institute, Brazil.
AB  - The Triatomines Collection of the Oswaldo Cruz Institute (CTIOC) holds 90
      holotypes, seven syntypes, and 619 paratypes of the family Reduviidae,
      distributed in 44 genera and nine subfamilies: Chryxinae, Emesinae, Hammacerinae,
      Harpactorinae, Peiratinae, Reduviinae, Stenopodainae, Triatominae, and Vesciinae.
      A detailed list containing nomenclatural, taxonomic, and locality information
      about all these types is herein presented for the first time. 

PMID- 25947431
TI  - Biogeographical regionalisation of the Andean region.
AB  - A biogeographic regionalisation of the Andean region is proposed as a
      hierarchical classification of sub-regions, provinces, sub-provinces and
      districts. It is based on biogeographic analyses of terrestrial plant and animal
      taxa, and seeks to provide universality, objectivity and stability. The Andean
      region is currently comprised of the Central Chilean, Subantarctic and Patagonian
      sub-regions and the South American transition zone, 15 provinces, five sub
      provinces and 81 districts. Complete synonymies and brief descriptions of the
      areas are provided, as well as the endemic taxa that diagnose the provinces. 

PMID- 25947433
TI  - Psocids from Malta (Insecta: Psocodea: 'Psocoptera'), with new synonymy for
      Peripsocus stagnivagus based on the discovery of its first Palaearctic male.
AB  - About 2,000 specimens of Psocoptera were collected in Malta recently. Examination
      of this material revealed 21 new records for the Maltese archipelago, augmenting
      the known psocid fauna of these islands from 6 to 27 species. One of the most
      abundant species is Peripsocus stagnivagus Chapman, 1930 (= P. bivari Baz, 1988 =
      P. leleupi Badonnel, 1976, new synonymies), formerly considered to be a
      predominantly Nearctic species. The discovery in Malta, of one male of this
      usually parthenogenetic species enabled comparison of this first Palaearctic male
      with the well-documented, rare Nearctic male. The lack of any morphological
      difference between these males, or between females from the Nearctic, the western
      Palaearctic and several Atlantic islands, supports the proposed synonymies. 

PMID- 25947432
TI  - Tetronarce cowleyi, sp. nov., a new species of electric ray from southern Africa
      (Chondrichthyes: Torpediniformes: Torpedinidae).
AB  - A new species of torpedo ray, Tetronarce cowleyi, sp. nov., is described from
      specimens collected from the southeastern Atlantic Ocean. The new species is
      placed in the genus Tetronarce based on a uniform dorsal coloration and absence
      of papillae around the spiracles. The new species is distinguished from its
      closest congeners, the North Atlantic Tetronarce nobiliana Bonnaparte, 1835, and
      southwestern Atlantic Tetronarce puelcha Lahille, 1926, by a combination of
      morphological characteristics including a shorter spiracular length, a
      proportionally greater head length as measured between snout margin and fifth
      gill openings, a proportionally greater preoral snout length, a uniform shiny
      black or dark gray dorsal surface, lacking any prominent markings, and a creamy
      white ventral color with dark edges in juveniles but fading with growth.
      Teteronarce cowleyi, sp. nov., is further distinguished from T. nobiliana by its
      more circular anterior disc shape (vs. relatively straight in T. nobiliana),
      fewer tooth rows (32/28 vs. 38-53/38-52 in T. nobiliana), greater mouth width
      (1.5-1.7 times as great as interorbital width vs. 0.5-0.6 times interorbital
      width in T. nobiliana), smaller distance between second dorsal and caudal fins
      (3.5-4.9% vs. 6.6-6.8% in T. nobiliana), and a clasper length extending nearly to
      lower caudal fin origin (claspers in T. nobiliana that extend only two-thirds
      distance between second dorsal and caudal fins). Teteronarce cowleyi, sp. nov.,
      is known from Walvis Bay, Namibia to Algoa Bay, Eastern Cape, South Africa, at
      depths of 110 to 457 m. 

PMID- 25947434
TI  - Biology, morphology and DNA barcodes of Tessaratoma javanica (Thunberg)
      (Hemiptera: Tessaratomidae).
AB  - Tessaratoma javanica (Thunberg) (Hemiptera: Tessaratomidae) an important sucking
      pest of litchi is studied for supplementing information on its biology,
      morphometrics of life stages and mtCOI (DNA barcodes). More details generated on
      the study add to the description of stages namely egg, 1st to 5th nymphal instars
      and adults. The evaluation of morphometrics of the life stages reveal that the
      progression of growth is more during 2nd to 3rd nymphal stages, and these are
      critical as far as the growth and development is concerned. The life cycle takes
      about 141.7+/-4.25 days; eggs last for 12.81+/-1.4 days with 97.14+/-2.86%
      hatchability; and duration of 1st , 2nd, 3rd, 4th and 5th nymphal instars were
      11.69+/-0.58, 7.23+/-0.2, 8.63+/-0.55, 13.04+/-0.55 and 26.31+/-0.97 days,
      respectively. In addition mtCOI analyses have been done employing standard 658 bp
      barcode fragments facilitating molecular diagnostics of the adults and other life
      stages and the phylogenetic tree with available sequence in the GenBank.

PMID- 25947435
TI  - Notes on Australian Laius Guerin-Meneville, Dicranolaius Champion and Intybia
      Pascoe with description of new species related to Dicranolaius c-purpureus (Lea)
      (Coleoptera: Melyridae: Malachiinae).
AB  - Remarks on Laius Guerin-Meneville and Dicranolaius Champion are provided. Laius
      falcifer Champion, 1921 is designated as the type species of Dicranolaius
      Champion, 1921. Dicranolaius bellulus is attributed to Boisduval (1835) not to
      Guerin-Meneville (1830). Dicranolaius c-purpureus (Lea) is redescribed and two
      closely related new species are described: D. weiri sp. n., and D. similis sp. n.
      Intybia Pascoe, 1866 is recorded from Australia for the first time and Laius
      filamentarius Lea, 1917 is regarded as member of Intybia comb. n.. 

PMID- 25947436
TI  - Notes on the genus Mada Mulsant with description of a new Andean species
      (Coleoptera: Coccinellidae: Epilachnini).
AB  - Mada andeana, a new species from the Andes is here described. Diagnostic
      characters are illustrated for both male and female. Mada durantae Gonzalez et
      Gomez is here synonymized with Mada inepta (Gorham), new synonymy. 

PMID- 25947437
TI  - A new species of the genus Gekko Laurenti (Squamata: Sauria: Gekkonidae) from
      Guangxi, China.
AB  - A new species of the genus Gekko is described on the basis of six specimens from
      Wuming county of Guangxi, southern China. Gekko kwangsiensis sp. nov. is
      distinguished from other congeners by a combination of the following characters:
      body relatively small (SVL 64.2-69.7 mm in adults), slender; nares in contact
      with rostral; internasal absent or single; postmentals two (rarely three),
      enlarged; interorbital scales between anterior corners of the eyes 29-31; dorsal
      tubercle rows 9-11; ventral scales between mental and cloacal slit 185-208;
      midbody scale rows 143-156; ventral scale rows 41-45; subdigital lamellae on
      first toe 11-13, on fourth toe 13-18; finger and toe webbing weakly developed;
      tubercles absent on upper surface of fore limbs and hind limbs; precloacal pores
      nine or ten in males, absent in females; postcloacal tubercle single; tubercles
      present on dorsal surface of tail base; subcaudals enlarged; dorsal surface of
      body with 9 or 10 thin light bands between nape and sacrum, and dorsal surface of
      tail with remarkable black and white bands. Data on the natural history of the
      new species are provided, and the number of species in the genus Gekko recorded
      from China is now 17. 

PMID- 25947438
TI  - Description of male of Dasypolia volynkini Ronkay, Ronkay, Gyulai & Pekarsky,
      2014 with data on bionomics of the species.

PMID- 25947439
TI  - A checklist of the helminth parasites of marine mammals from Argentina.
AB  - Based on published records and new data accumulated by the authors, we generated
      a list of the helminth parasites of marine mammals from off the coast of
      Argentina. We found 49 reports of helminths parasitizing cetaceans and pinnipeds
      from Argentina from 1952 to 2015. The list includes 54 taxa of helminths (8
      acanthocephalans, 24 nematodes, 11 cestodes and 11 trematodes) associated with 18
      species of cetaceans and 5 species of pinnipeds. Most of the records represent
      adults (5 acanthocephalans, 16 nematodes, 6 cestodes and 11 trematodes), followed
      by larvae (10 nematodes and 3 metacestodes) and juveniles (4 acanthocephalans and
      2 cestodes). The checklist contains 24 named species (5 acanthocephalans, 8
      nematodes, 4 cestodes and 7 trematodes) and 30 undetermined helminth taxa (3
      acanthocephalans, 16 nematodes, 7 cestodes and 4 trematodes). The present account
      contains a parasite/host lists and information on the habitat, developmental
      stage and distribution of the parasites listed, repositories of their type and
      voucher specimens and references. A host-parasite list is also presented. The
      data compiled on the helminth of marine mammals from Argentina in the present
      study revealed gaps in the knowledge of their taxonomic identification,
      composition, distribution, host specificity and life cycles. These gaps are also
      briefly discussed in order to provide an outline for future research. 

PMID- 25947440
TI  - Some taxonomic and nomenclatural changes in American Mantodea (Insecta,
      Dictyoptera)--Part I.
AB  - Multiple nomenclatural problems persist in mantodean taxonomy. This constitutes
      an important challenge for praying mantis systematics, its forthcoming
      development and future consolidation. In this first contribution, we attempt
      solving a number of issues involving mostly Neotropical praying mantis species
      described by Brazilian entomologists Paulo S. Terra, Candido F. de Mello-Leitao,
      Salvador de Toledo Piza Junior and Lauro J. Jantsch. We provide evidence to
      justify the following nomenclatural changes. In Acanthopidae, Acontiothespis
      travassosi Jantsch, 1986 is a new synonym of Raptrix perspicua (F. 1787). Changes
      in Thespidae are: Emboicy Terra, 1982 is a new synonym of Chloromiopteryx Giglio
      Tos, 1915, E. mirim Terra, 1982 is transferred to Chloromiopteryx as C. mirim
      (Terra, 1982) (new combination); Musoniola plurilobata Mello-Leitao, 1937 is
      transferred to Chloromiopteryx as C. plurilobata (Mello-Leitao, 1937) (new
      combination); Metathespis modesta Piza, 1968 is removed from synonymy with
      Chloromiopteryx thalassina (Burmeister, 1838) and considered valid as C. modesta
      (Piza, 1968) (new combination and status revalidated); Metathespis precaria Piza,
      1968 is removed from synonymy with Chloromiopteryx thalassina (Burmeister, 1838)
      and considered a new synonym of Miobantia rustica (Fabricius, 1781); Eumiopteryx
      magna Jantsch, 1991 is transferred to Anamiopteryx as A. magna (Jantsch, 1991)
      (new combination). For Mantidae/Amelinae, Tithrone corseuli Jantsch, 1986 and T.
      clauseni Jantsch, 1995 are new synonyms of Litaneutria minor (Scudder, 1872); in
      Mantidae/Photininae Coptopteryx gigliotosi Piza, 1960 (non Werner, 1925), its
      replacement name Coptopteryx ermannoi Jantsch & Corseuil, 1988 and Paraphotina
      precaria Piza, 1966 (the latter currently placed within Coptopteryx) are all new
      synonyms of Coptopteryx argentina (Burmeister, 1838), whereas Brachypteromantis
      bonariensis Piza 1960 (currently placed among Coptopteryx) is a new synonym of
      Coptopteryx gayi (Blanchard, 1851); Tithrone major Piza, 1962 is transferred to
      Orthoderella as O. major (Piza, 1962) (new combination); Orthoderella
      brasiliensis Roy & Stiewe, 2011 is a new synonym of Orthoderella major (Piza,
      1962); Tithrone catharinensis Piza, 1962 is a new synonym of Photina vitrea
      (Burmeister, 1838); Margaromantis Piza, 1982, Rehniella Lombardo, 1999,
      Colombiella Kocak & Kemal, 2008 and Lombardoa Ozdikmen, 2008 are all new synonyms
      of Photiomantis Piza, 1968 (status revalidated); Metriomantis planicephala Rehn
      1916 is transferred to Photiomantis as P. planicephala (Rehn, 1916) (new
      combination) and Photiomantis silvai Piza, 1968 is considered a new synonym of
      Photiomantis planicephala (Rehn, 1916);  Margaromantis nigrolineata Menezes &
      Bravo, 2015 is transferred to Photiomantis as P. nigrolineata (Menezes & Bravo,
      2015) (new combination). In Mantidae/Vatinae, Uromantis amazonica Jantsch, 1985
      and Uromantis paraensis Jantsch, 1985 (currently placed among Stagmomantis), are
      new synonyms of Chopardiella latipennis (Chopard, 1911), while Pseudovates
      hyalostigma Mello-Leitao, 1937 and Vates obscura Toledo Piza, 1983 are new
      synonyms of V. biplagiata Sjostedt, 1930. Lectotypes are designated for
      Chloromiopteryx thalassina (Burmeister, 1838) and Orthoderella major (Piza,
      1962). Finally, we provide supplementary information about the works of S. de T.
      Piza and L. J. Jantsch, and a necessary critical assessment of their taxonomic
      contributions to the Mantodea. 

PMID- 25947441
TI  - Revision of the Dysmorphoptilidae with emarginate tegmina (Hemiptera:
      Auchenorryncha: Cicadomorpha: Prosboloidea) of the Queensland Triassic.
AB  - Species of the extinct family Dysmorphoptilidae with distinctly punctate and
      emarginate tegmina are one of the most characteristic elements of the hemipteran
      fauna of the three Queensland Triassic fossil insect-bearing formations-the
      Middle Triassic (Anisian) Gayndah Formation at Gayndah, the Late Triassic
      (Norian) Mount Crosby Formation at Mount Crosby, and the Late Triassic (Norian)
      Blackstone Formation at Mount Crosby and Dinmore. Eight species in five genera
      have been identified: Mesocixius triassicus Tillyard, 1919 (Denmark Hill),
      Mesocixius parvus (Evans) comb. nov., 1956 (Mount Crosby), Triassocixius
      australicus Tillyard, 1919 (Denmark Hill), Carsburgia knezouri gen. et sp. nov.
      (Dinmore), Dysmorphoptiloides elongata Evans, 1956 (Mount Crosby),
      Dysmorphoptiloides ellisi sp. nov. (Gayndah), Tennentsia princeps sp. nov. (Mount
      Crosby), and Tennentsia evansi sp. nov. (Gayndah). Synapomorphies are proposed to
      suggest that Triassocixius, Carsburgia, Dysmorphoptiloides and Tennentsia are
      monophyletic. Mesocixius may be paraphyletic, its two species sharing only
      apparently plesiomorphic characters. The limits and relationships of the over 15
      described world genera of the Dysmorphoptilidae remain poorly known, but
      examination of the Queensland species has identified several characters which may
      be of cladistic value: the presence or absence of a strigil, the degree of tegmen
      emarginations and form of the resultant apical lobe, the presence and form of
      swellings on the claval margin, the pattern of tegmen punctation, the
      relativities of the primary forks of R and RA, the branching pattern of RA1, the
      branching and orientation of RA2,and the presence or absence of a fusions between
      RA and RP distally and between M and CuA basally. 

PMID- 25947442
TI  - The identity of Acanthosoma vicinum, with proposal of a new genus and species
      level synonymy (Hemiptera: Heteroptera: Acanthosomatidae).
AB  - The identity of Acanthosoma vicinum Uhler, 1861 (type species of the monotypic
      genus Grossaria Kumar, 1974) is clarified based on reexamination of the
      lectotype. The following new combination and new subjective synonymies are
      proposed: Elasmucha Stal, 1864 = Grossaria Kumar, 1974, syn. nov.; Elasmucha
      vicina (Uhler, 1861), comb. nov. (transferred from Acanthosoma) = Elasmucha
      dorsalis (Jakovlev, 1876), syn. nov. Reversion to the senior name E. vicina is
      considered to be undesirable, therefore, in order to preserve stability, no
      nomenclatural changes are proposed in this paper, but an application has
      simultaneously been submitted to the International Commission on Zoological
      Nomenclature to give the specific name dorsalis precedence over the specific name
      vicinum. 

PMID- 25947443
TI  - A revision of the Chinese species of Cyamophiliopsis (Hemiptera: Psylloidea:
      Psyllidae) associated with Spiraea (Rosaceae).
AB  - Cyamophiliopsis is a small genus restricted to the Palaearctic Region and
      associated with Spiraea spp. (Rosaceae). In the present work, following five
      species are recognized in China: C. pseudofasciata sp. nov., C. sarmatica, C.
      spinosa sp. nov., C. xinjiangana sp. nov. and C. zaisani. Cyamophiliopsis is
      diagnosed, redescribed in detail, and its phylogenetic relationships are
      discussed. All the species are described or redescribed, and the fifth instar
      immature of C. zaisani is described for the first time. Nomenclatorial problems
      are discussed concerning the Far East Russian Psylla spiraee which is transferred
      to Cyamophiliopsis as C. spiraee comb. nov. 

PMID- 25947444
TI  - Palaearctic Chelostoma bees of the subgenus Gyrodromella (Megachilidae, Osmiini):
      biology, taxonomy and key to species.
AB  - Gyrodromella represents a subgenus of the osmiine bee genus Chelostoma
      (Megachilidae) containing eight species, which are confined to the Palaearctic
      region. Analysis of female pollen loads, field observations and literature data
      suggest that all C. (Gyrodromella) species are oligolectic harvesting pollen
      exclusively on flowers of Campanula and possibly also closely related
      Campanulaceae genera. Preexisting linear cavities in dead wood or stems serve as
      nesting sites and mud partly combined with pebbles is used for the construction
      of cell partitions and nest plug. The taxonomic revision of C. (Gyrodromella)
      revealed the existence of two undescribed species: C. clypeale spec. nov. from
      central and eastern Turkey, and C. tonsum spec. nov. from eastern Turkey.
      Chelostoma confusum (Benoist, 1934) and C. proximum Schletterer, 1889 are newly
      synonymized with C. rapunculi (Lepeletier, 1841), and a lectotype of C.
      handlirschi Schletterer, 1889 is designated. Keys for the identification of all
      C. (Gyrodromella) species are given. 

PMID- 25947445
TI  - Review of the leafhopper genus Oncopsis Burmeister (Hemiptera: Cicadellidae:
      Macropsinae) in China with descriptions of two new species.
AB  - Two new macropsine species, Oncopsis latusoid sp. nov. and O. taibaiensis sp.
      nov. are described and illustrated from China. A checklist and illustrated key to
      Chinese species of this genus are given. 

PMID- 25947446
TI  - Ocelliemesina sinica, the second ocelli-bearing genus and species of thread
      legged bugs (Hemiptera: Reduviidae: Emesinae).
AB  - Ocelliemesina sinica, gen. & sp. nov., from Yunnan Province, China is described.
      It represents the second genus and species with ocelli in the reduviid subfamily
      Emesinae. Dorsal habitus, male genitalia, and other diagnostic morphological
      characters of the new species are illustrated. The type specimen is preserved in
      the Entomological Museum of China Agricultural University, Beijing. 

PMID- 25947447
TI  - Ctenophores from the Oaxaca coast, including a checklist of species from the
      Pacific coast of Mexico.
AB  - Ctenophores are poorly known in the tropical eastern Pacific, including the
      southern coast of Mexico. Previous records of ctenophores along the Pacific coast
      have been provided mainly from northern waters. For the coast of Oaxaca state,
      their occurrence has only been mentioned before at phylum level. In this paper,
      we provide the first three records of ctenophores for the Oaxacan coast, which
      represent new records of Beroe forskalii and Bolinopsis vitrea as well as the
      first record of Ocyropsis maculata in the tropical eastern Pacific. Descriptions
      of these three species, as well as a checklist of the ctenophores from the west
      coast of Mexico are provided. 

PMID- 25947448
TI  - Two new species and additional data of Gabrius Stephens (Coleoptera,
      Staphylinidae) from the Korean Peninsula.
AB  - Two new species of Gabrius Stephens from the Korean Peninsula are described:
      Gabrius koreanus (S-Korea) and G. makranczyi (N- and S-Korea). Gabrius
      ponghwaricus Pasnik, 2000 is synonymized with G. ancoripenis Cho & Lee, 1997. New
      records: Gabrius mandschuricus Bernhauer, 1914 (S-Korea), G. philomimus
      Schillhammer, 2000 (Korean Peninsula). 

PMID- 25947449
TI  - New data on the genus Hybos Meigen (Diptera: Hybotidae) from the Palaearctic
      Region.
AB  - The taxonomy and distribution of the genus Hybos Meigen in the Palaearctic Region
      is reviewed with a special reference to the European fauna. Twenty-three species
      have been recorded from the Palaearctic, of which only four species are known
      from Europe. We describe two new species, H. andradei sp. nov. (Portugal) and H.
      mediasiaticus sp. nov. (Middle Asia). The status of two previously considered
      doubtful species of Hybos are validated: H. striatellus Villeneuve, 1913
      (Algeria) and H. vagans Loew, 1874 (the Caucasus). Both species are re-described,
      and the lectotype of H. striatellus is designated. A key to species of Hybos from
      the western Palaearctic is compiled. Numerous new data on distributions of H.
      culiciformis (Fabricius, 1775), H. femoratus (Muller, 1776), H. grossipes (Linne,
      1767) and H. vagans are given. Hybos culiciformis is recorded for the first time
      from Algeria, Byelorussia, Croatia, Cyprus, Lebanon, and Portugal; H. femoratus
      from Estonia, Georgia (including Abkhazia), Kazakhstan, Mongolia and Ukraine; H.
      grossipes-from Byelorussia, Estonia, Kazakhstan, Latvia, Mongolia, Ukraine; H.
      vagans-from Armenia, Azerbaijan, Georgia (including Abkhazia), Russia, Turkey.
      The variation of some characters in H. culiciformis is discussed and is confirmed
      for Portugese specimens by COI barcoding. Female postabdominal structures are
      examined and described for H. andradei sp. nov., H. culiciformis, H. femoratus,
      H. grossipes, H. mediasiaticus sp. nov., and H. striatellus. Possible
      relationships of the West-Palaearctic species are discussed. A check-list of
      Hybos from the Palaearctic Realm is provided. 

PMID- 25947450
TI  - Morphological, morphometric and genetic variation among cryptic and sympatric
      species of southeastern South American three-striped opossums (Monodelphis:
      Mammalia: Didelphidae).
AB  - Monodelphis is the most diverse genus of the family Didelphidae, whose
      systematics and taxonomy have not yet been well established. Two of the included
      species, Monodelphis americana and M. iheringi, are difficult to distinguish
      because both present three dorsal black stripes. Furthermore, they show intra-
      and interspecific variation related to body size and pelage coloration. Because
      this variation is not well understood, there are problems in correctly
      identifying these species, which remain poorly collected and thus rare in
      zoological collections. This study evaluated the morphological and genetic
      variations in a sample of striped opossums from a single location in southeastern
      Brazil to understand if the morphological variation observed in individuals from
      the same location was indicative of the existence of more than one taxon. The
      comparative analyses of a series from this single locality with museum specimens
      of other locations revealed variations in the skin and skull qualitative
      characters that were related to age and sex. Morphological comparisons led to the
      identification of two morphogroups, which were corroborated by molecular data;
      the analysis of cytochrome b sequences indicated the existence of two clades,
      with an average divergence of 14%. Thus, the results support the existence of two
      taxa in the sample, defined as M. americana and M. iheringi. We confirmed the
      sympatry of these two species in a location in southeastern Brazil, presented
      morphological diagnostic characters to distinguish the two species, provided
      novel phylogenetic information on the group, and also demonstrated the existence
      of important intra- and interspecific morphological variations related to sexual
      dimorphism and ontogeny in the group. These results significantly contribute to
      information on the systematics of the genus. 

PMID- 25947451
TI  - Eusyllinae and "Incertae sedis" syllids (Annelida: Syllidae) from South America,
      with a new species from Brazil and a new combination for a Peruvian species.
AB  - We herein present the first taxonomic account on the genera Amblyosyllis,
      Brevicirrosyllis, Eusyllis and Opisthodonta from Brazilian waters, with the
      description of Eusyllis nonatoi sp. nov. The new species is characterized by
      having transverse dark stripes on dorsum, unidentate, relatively short falciger
      blades with inverted dorso-ventral gradation in length, and distally rounded to
      inconspicuously bifid dorsal simple chaetae. In adittion, the description of
      Eusyllis liniata comb. nov., from Peru, originally described as belonging to
      Odontosyllis, is also provided. Finally, we amend the description of Opisthodonta
      russelli, originally described from anterior fragments only. 

PMID- 25947452
TI  - Description of a new species of the Miniopterus aelleni group (Chiroptera:
      Miniopteridae) from upland areas of central and northern Madagascar.
AB  - Recent molecular genetic work, combined with morphological comparisons, on
      Malagasy members of the bat genus Miniopterus (Family Miniopteridae), has
      uncovered a number of cryptic species. Based on recently collected specimens and
      associated tissues, we examine patterns of variation in M. aelleni, the holotype
      of which comes from Ankarana in northern Madagascar. Using molecular genetic
      (mitochondrial cytochrome b) and morphological characters we describe a new
      species, M. ambohitrensis sp. nov. In northern Madagascar, M. ambohitrensis and
      M. aelleni are allopatric, but occur in relatively close geographical contact
      (approximately 40 km direct line distance) with M. ambohitrensis found at
      Montagne d'Ambre in montane humid forest and M. aelleni sensu stricto at Ankarana
      in dry deciduous forest. Morphologically, this new taxon is differentiated from
      M. aelleni based on pelage coloration, external measurements, craniodental
      differences, and tragus shape. Comparisons using 725 bp of cytochrome b found a
      divergence of 1.1% within M. aelleni sensu stricto, 0.8% within M. ambohitrensis,
      and 3.3% between these two clades. The two sister species do not demonstrate
      acoustical differences based on recordings made in a flight cage. Miniopterus
      ambohitrensis is known from four localities in the northern and central portions
      of Madagascar, all from montane regions and across an elevational range from
      about 800 to 1600 m; its calculated "Extent of occurrence" is 15,143 km2. It is
      possible that this species is at least partially migratory.

PMID- 25947453
TI  - Macrobrachium indianum (Decapoda: Palaemonidae), a new species of hill stream
      prawn from Pambar River, Kerala, India.
AB  - Macrobrachium indianum new species is described from the Pambar River, Kerala, S.
      India. The species shares certain characters with M. gurudeve Jayachandran &
      Raji, 2004, M. bombayense Almelker & Sankolli, 2006 and M. kulkarnii Almelker &
      Sankolli, 2006, while it differs remarkably from these three species in
      distinctive diagnostic characters: rostral formula 7-8/3-4 with 1 postorbital
      teeth, one tooth above orbit; carapace smooth with distal end of rostrum directed
      downwards; cephalothorax longer than rostrum; in second chelate leg, proximal
      cutting edge of movable finger with two weak denticles, one weak denticle in
      immovable finger, carpus longer than merus, merus shorter than propodus and
      longer than ischium; dactylus the shortest podomere. Five thick and a few thin
      reddish brown bands of chromatophores are seen on carapace. Pigmentation is found
      mid and ventro-laterally on abdominal segments, pereiopods have chromatophores at
      the distal part of podomeres. 

PMID- 25947454
TI  - Cosmosycanus perelegans (Hemiptera: Reduviidae: Harpactorinae), a new record from
      China, with report of its female genitalia.
AB  - The oriental genus Cosmosycanus Ishikawa & Tomokuni, 2004 and the species
      Cosmosycanus perelegans (Breddin, 1903) are newly  recorded from China.
      Cosmosycanus perelegans is redescribed and  illustrated. The female genitalia is
      reported for the first time. The variations of colour patterns and male genital
      structures among Chinese and Vietnamese individuals are briefly noted. 

PMID- 25947455
TI  - Redescription of Pethia melanomaculata (Teleostei: Cyprinidae) from Sri Lanka.
AB  - The name Pethia melanomaculata (Deraniyagala) is available for the Sri Lankan
      fish previously referred to P. ticto, being distinguished from its Indian
      congeners by the combination of the following characters; having 1/24/1/31/2
      scales in transverse line on body; body depth 32.4-41.5% of standard length (SL);
      head length (HL) 26.1-29.2% of SL; snout length 25.3-35.6% of HL; eye diameter
      24.4-31.9% of HL; a small black humeral spot on lateral-line scales 3 or 4; a
      black spot on caudal peduncle, on scales 16-18 of the lateral line series; 3
      unbranched dorsal-fin rays, the last one strongly serrated, with 8-11 serrae. 

PMID- 25947456
TI  - The genus Platytenerus Miyatake, 1985 (Coleoptera: Cleridae: Neorthopleurinae),
      with description of a new species from Japan.
AB  - The genus Platytenerus Miyatake, 1985 (Coleoptera: Cleridae) is redescribed and
      classified into the subfamily Neorthopleurinae Opitz, 2009. A phylogenetic tree
      is supplementally provided for Platytenerus based on twenty morphological and two
      geographical characters. A new species of the genus, Platytenerus iriomotensis
      sp. n. is described from Iriomote Island, Okinawa, Japan. 

PMID- 25947457
TI  - A new species of Tribonium Saussure, 1862 from the Province of Misiones,
      Argentina (Blattaria, Blaberidae, Zetoborinae).
AB  - Tribonium rothi sp. n. is described from Argentina, whereas T. neospectrum and T.
      conspersum are recorded for the first time for that country, and their genitalia
      is redescribed. Femur and tibial spine armature are given and Tribonium is
      compared with Schistopeltis. A key to identify species of the genus Tribonium
      recorded in Argentina is provided. 

PMID- 25947458
TI  - LECH BOROWIEC & JOLANTA WIETOJANSKA (2014)  A revision of the genus Herminella
      Spaeth (Chrysomelidae: Cassidinae: Notosacanthini), with a description of a new
      related genus and species from Madagascar. Zootaxa, 3892(2): 257-272.

PMID- 25947459
TI  - Revision of the genus Pseudopomatias and its relatives (Gastropoda:
      Cyclophoroidea: Pupinidae).
AB  - The present paper revises all species that have been assigned to Pseudopomatias
      Mollendorff, 1885 and Nodopomatias Gude, 1921. The following new species are
      described: Pseudopomatias abletti Pall-Gergely, n. sp. (northeastern India),
      Pseudopomatias harli Pall-Gergely, n. sp. (northeastern India), Pseudopomatias
      linanprietoae Pall-Gergely n. sp. (Laos), Pseudopomatias maasseni Pall-Gergely &
      Hunyadi, n. sp. (Vietnam and China), Pseudopomatias nitens Pall-Gergely n. sp.
      (Vietnam), Pseudopomatias prestoni Pall-Gergely, n. sp. (northeastern India),
      Pseudopomatias reischuetzi Pall-Ger-gely, n. sp. (north-eastern India),
      Pseudopomatias shanensis Pall-Gergely n. sp. (Myanmar) and Pseudopomatias sophiae
      Pall-Gergely, n. sp. (Vietnam). Pseudopomatias fulvus is moved to the synonymy of
      P. amoenus. Csomapupa n. gen. is erected for Pseudopomatias grandis and P.
      luyorensis. Another new genus, Vargapupa is erected with two species, namely
      Vargapupa biheli Pall-Gergely, n. sp. (Vietnam) and V. oharai Pall-Gergely, n.
      sp. (Laos). Both new genera are probably closely related to Pseudopomatias and
      Nodopomatias. All the currently available type specimens of species in these
      groups are figured. Anatomical information of P. eos and DNA sequence data of two
      Pseudopomatias species indicate that the genus is a member of the family
      Pupinidae. The other pre-existing hypothesis, namely that Pseudopomatias is a
      member of the Cochlostomatidae, is not supported by our results. 

PMID- 25947460
TI  - Habronyx Forster (Hymenoptera: Ichneumonidae: Anomaloninae) in Peru and Ecuador:
      three new species, a range extension, and a new host record.
AB  - The ichneumonid genus Habronyx is recorded for the first time from Peru and
      Ecuador, and three new species are described and figured-Habronyx (Camposcopus)
      flavus Alvarado, new species, H. (Habronyx) nigrofasciata Alvarado, new species,
      and H. (H.) saqsaywaman Alvarado, new species. Hadronyx (H.) punensis is recorded
      for the first time in Peru. Habronyx (H.) nigrofasciata was reared from Paracles
      tapina (Dyar, 1913) (Erebidae: Arctiinae). In addition, the distribution of P.
      tapina is expanded and figures of its larvae, pupae, and adult female and male
      are provided. 

PMID- 25947462
TI  - Larval and pupal morphology of three species of the genus Psammoecus Latreille
      (Coleoptera: Silvanidae: Brontinae) in Japan with reference to the number of
      larval instars.
AB  - The last instar larva and the pupa of Psammoecus scitus Yoshida & Hirowatari, all
      instar larvae of P. simoni Grouvelle, and the last instar larva of P. hiranoi
      Yoshida & Hirowatari are described, and their morphologies are compared among
      species and instars. Larval association for P. simoni was confirmed by DNA
      barcoding. Apart from a brief description of the pupa of Cryptamorpha brevicornis
      (White) illustrated by Hudson (1924), the pupal morphology of Brontinae is
      described in detail for the first time. Potentially informative characters for
      phylogeny of larval and pupal morphology of Silvanidae are discussed. 

PMID- 25947461
TI  - Revision and phylogeny of narrow-mouthed treefrogs (Cophyla) from northern
      Madagascar: integration of molecular, osteological, and bioacoustic data reveals
      three new species.
AB  - We provide a revision of microhylid treefrogs of the genus Cophyla, the type
      genus of the subfamily Cophylinae. A phylogeny inferred from DNA sequences of
      multiple mitochondrial and nuclear genes, with representatives of all cophyline
      genera except Madecassophryne and including representatives of the two most
      divergent intrageneric lineages within Cophyla, placed Cophyla as sister group of
      Platypelis and confirmed both genera as reciprocally monophyletic. We describe
      three new Cophyla species based on osteological, morphological and bioacoustic
      characters as well as genetic differentiation in one nuclear and several
      mitochondrial markers. As in the vast majority of cophylines, all species of
      Cophyla emit long, stereotyped repetitions of a single tonal note, and we here
      consider one of these notes as a call; call duration thus equals note duration
      and the intervals between calls are named inter-call intervals. Cophyla maharipeo
      sp. nov. collected in Joffreville and Foret d'Ambre Special Reserve (adult SVL 22
      27 mm) is characterized by having long calls (1166-1346 ms) with long inter-call
      intervals (2154-3881 ms). Cophyla noromalalae sp. nov. collected in Montagne
      d'Ambre National Park (adult SVL 22-29 mm) is characterized by having short calls
      (662-821 ms) and short inter-call intervals (874-1882 ms). Cophyla puellarum sp.
      nov., also from Montagne d'Ambre National Park, is larger than the other two
      species (adult SVL 27.3-33.6 mm) and characterized by the shortest calls (326-390
      ms) and long inter-call intervals (1961-3996 ms). Osteological analyses based on
      micro-CT scans and cleared and stained specimens confirms that the shape of the
      posterior vomer (centrally divided vs. undivided) may be a useful character to
      diagnose most species as belonging to either Platypelis and Cophyla, and suggest
      the absence of clavicles (present in Platypelis) is a derived character of most
      Cophyla. However, clavicles were present in C. puellarum, the only known Cophyla
      occurring at relatively high elevations (1250-1300 m a.s.l.) while otherwise in
      northern Madagascar, forests at higher elevations up to 2700 m a.s.l. are
      occupied by Platypelis species. Cophyla maharipeo was found at relatively low
      elevations (630-720 m a.s.l.), similar to the three previously known congeners
      (C. berara, C. occultans, C. phyllodactyla). Cophyla noromalalae occurs at
      intermediate elevations (900-1050 m a.s.l.). The molecular phylogeny inferred
      herein suggests that the ancestor of a clade containing all Cophyla species
      except C. puellarum evolved a modified shoulder girdle structure without ossified
      clavicles, and adapted to low-elevation habitats. 

PMID- 25947463
TI  - New feather mites of the genera Aniacarus and Aniibius (Acariformes:
      Pterolichidae) from two cuckoo species (Cuculiformes: Cuculidae) in Brazil.
AB  - Five new species of the family Pterolichidae are described from two common non
      parasitic cuckoo species of the subfamily Crotophaginae (Cuculiformes: Cuculidae)
      in Brazil: Aniacarus ani sp. n. from the Smooth-billed Ani, Crotophaga ani
      Linnaeus, A. simplex sp. n., A. robustus sp. n., A. coronatus sp. n. and Aniibius
      guirae sp. n. from the Guira Cuckoo, Guira guira (Gmelin). A key to all known
      species of Aniacarus is provided. All four pterolichid species associated with
      the G. guira can occur simultaneously on one host individual. A brief review of
      studies of feather mites associated with Cuculidae is given. 

PMID- 25947464
TI  - Acrotritia species (Acari: Oribatida: Euphthiracaridae) from China with
      description of a new species.
AB  - In this paper, eight species of Acrotritia (Acari: Oribatida: Euphthiracaridae)
      are identified, including a new species, Acrotritia tibetensis sp. nov., and four
      newly recorded species from China: Acrotritia gracile (Niedbala, 2000),
      Acrotritia hauseri (Mahunka, 1991), Acrotritia refracta (Niedbala, 1998) and
      Acrotritia simile (Mahunka, 1982). An updated diagnosis of the genus and remarks
      on some known species are presented, the validity of species A. hauseri is
      discussed, and a key to Chinese known species of Acrotritia is also provided. 

PMID- 25947465
TI  - Description of a new species of Sparassocynus (Marsupialia: Didelphoidea:
      Sparassocynidae) from the late Miocene of Jujuy (Argentina) and taxonomic review
      of Sparassocynus heterotopicus from the Pliocene of Bolivia.
AB  - A new species of sparassocynid marsupial, Sparassocynus maimarai n. sp. from the
      late Miocene of Maimara Formation (Jujuy Province, Argentina) is described from a
      left mandibular fragment with a complete p2-m4 series. It differs from the
      remaining species of the genus S. bahiai (Montehermosan-late Miocene/early
      Pliocene-of Buenos Aires Province, Argentina) and S. derivatus (Chapadmalalan and
      Marplatan-Pliocene of Buenos Aires Province) by its smaller size, the relatively
      longer m1 with respect to the m4, the presence of a lingual cingulum extended
      between para- and metaconid on the m1-3, and its more robust entoconids. As part
      of this study the taxonomic status of Sparassocynus heterotopicus (Montehermosan,
      Umala, Bolivia; Pliocene) was reviewed concluding that this taxon should be
      referred to as 'Sparassocynus' heterotopicus and considered a Didelphoidea of
      uncertain affinities. Sparassocynus maimarai n. sp. is the oldest records of the
      genus, adding new information to evaluate the origins and early diversification
      of sparassocynids. Sparassocynus maimarai n. sp. was recovered with precise
      stratigraphic control, highlighting its potential biostratigraphic significance
      to the temporal correlations between Maimara Formation and other Mio-Pliocene
      stratigraphic units from the northwestern Argentina. 

PMID- 25947466
TI  - Morphological variation, advertisement call, and tadpoles of Bokermannohyla
      nanuzae (Bokermann, 1973), and taxonomic status of B. feioi (Napoli & Caramaschi,
      2004) (Anura, Hylidae, Cophomantini).
AB  - Bokermannohyla nanuzae (Bokermann & Sazima 1973) and B. feioi (Napoli &
      Caramaschi 2004) belong to the B. cir-cumdata species group. The type locality of
      the former is Serra do Cipo, Espinhaco mountain range, and of the latter is
      Parque Estadual do Ibitipoca, Mantiqueira mountain range, both in Minas Gerais
      State, Brazil. Differences on dorsal draw-ing pattern of adults, oral disc
      morphology of tadpoles, and temporal properties of calls were proposed to
      distinguish these two species. However, several specimens found between the two
      type localities remain unidentified because diagnostic characters and states
      occur in all of these populations. Thus, in order to assess these characters
      variations, we performed an analysis of the morphology and morphometry of adults,
      vocalization, and morphology of tadpoles. Specimens were divided into three
      operational taxonomic units (OTUs): B. nanuzae (Serra do Cipo and northwards,
      Espinhaco mountain range), B. cf. nanuzae (Quadrilatero Ferrifero, Espinhaco
      mountain range, south of Serra do Cipo), and B. feioi (Serra do Ibitipoca,
      Mantiqueira mountain range). Drawing patterns of the dorsum and limbs show clinal
      variation and the three units are morphometrically very similar. Temporal and
      spectral properties of calls overlap in these three units. The diagnostic
      differences originally proposed for tadpoles are intrapopulational variations and
      occur in specimens from all of the locations analyzed. We found that these three
      units are morphologically indistinguishable. Therefore, we designate Bok
      ermannohyla feioi (Napoli & Caramaschi 2004) as a junior synonym of
      Bokermannohyla nanuzae (Bokermann & Sazima 1973), extending its geographical
      distribution to the Mantiqueira mountain range.

PMID- 25947467
TI  - Studies of Bolivian Ptiliidae (Coleoptera) 1: The genus Cissidium Motschulsky
      with six new species.
AB  - This is the first report on a collection of Ptiliidae from Bolivian forest leaf
      litter made by Dr Petr Banar of the Brno Museum (Czech Republic). Six new species
      in the genus Cissidium Motschulsky, are described and figured: C. amboroensis,
      sp. n., C. globosum, sp. n., C. elongatum, sp. n., C. lisae sp. n., C. petri sp.
      n. and C. tigrum, sp. n.. The relationship of Cissidium to Dacrysoma Grebennikov
      and its position in the tribe Discheramocephalini is discussed, and the generic
      description revised so as to encompass all valid species. 

PMID- 25947468
TI  - Proposal of Whittingtonocotyle n. gen. (Dactylogyroidea: Dactylogyridae), with
      the description of two new species from the gills of Hoplerythrinus unitaeniatus
      (Characiformes: Erythrinidae) in Brazil.
AB  - Whittingtonocotyle n. gen. is proposed for species with a male copulatory organ
      sclerotized, spiral, clockwise, non-articulated to the accessory piece; prostatic
      reservoir separated into two/three zones with one or two terminal areas densely
      stained; vaginal opening dextrodorsal; anchors without well-defined roots; and
      dorsal bar with anteromedial protuberance. Two new species of Whittingtonocotyle
      n. gen. are described from the gills of Hoplerythrinus unitaeniatus (Agassiz),
      from two rivers of the State of Para, Brazil. Whittingtonocotyle caetei n. sp.
      (type species) is characterized by possessing ventral anchor with deep root
      truncate; prostatic reservoir separated into two zones with one terminal area
      densely stained; and vaginal canal heavily sclerotized, coiled and dilate
      distally. Whittingtonocotyle jeju n. sp. is distinguished from the previously
      species mainly by having a male copulatory organ comprising a coil of about 19
      rings (29 rings in Whittingtonocotyle caetei n. sp.); a prostatic reservoir
      separated into three zones with two terminal areas densely stained; vaginal canal
      sclerotized, sigmoid; and dorsal bar with short anteromedial process (elongate in
      Whittingtonocotyle caetei n. sp.). 

PMID- 25947470
TI  - A new species, Simulium (Nevermannia) berchtesgadense (Diptera: Simuliidae), and
      its chromosomes, from the Alps of southeastern Germany.
AB  - Simulium (Nevermannia) berchtesgadense nov. spec. is described from the Alps of
      southeastern Germany. The morphology and diagnostic characters for all life
      stages except the egg are given, and the polytene chromosomes are compared with
      those of other members of the Simulium (Nevermannia) vernum group. The species is
      chromosomally similar to Simulium (Nevermannia) cryophilum cytoform 'A' but
      differs morphologically in each life stage. Bionomic information and the
      associated simuliid fauna are presented. 

PMID- 25947469
TI  - Morphology and morphometry of Lycaenid eggs (Lepidoptera: Lycaenidae).
AB  - A morphological study with the use of scanning electron microscope of 67 species
      of Iberian Lycaenidae is presented. The study covers all the genera present in
      the area and shows an extraordinary variation in chorionic characters that allows
      egg diagnosis for most species. A morphometric study showed that the eggs from
      the sample have sizes that are correlated with adult size, but some species
      showed larger egg size than expected. Species hibernating at the egg stage proved
      to have on average larger sizes than those overwintering at other stages,
      probably because this trait might be favourable to endure the adverse conditions
      taking place during the winter. A cladistic analysis was performed using
      morphologic and morphometric characters from the egg with the result of poor
      discriminant power. However, some formal taxonomic groups such as the genera
      Lycaena and Satyrium were supported by our analysis due to specific apomorphic
      characters. 

PMID- 25947471
TI  - An annotated catalogue of the type material of Elateroidea Leach, 1815
      (Coleoptera) deposited in the Coleoptera collection of the Museum of Zoology of
      the University of Sao Paulo, Brazil.
AB  - The Museum of Zoology of the University of Sao Paulo (MZSP) houses one of the
      most important Coleoptera collections of Brazil and Neotropical Region with
      nearly 900,000 adult mounted material and about 1,500,000 specimens to be
      mounted. The superfamily Elateroidea Leach, 1815 (including Cantharoidea)
      comprises about 24,077 described species in 17 families. The MZSP owns type
      material of Brachypsectridae LeConte & Horn, 1883, Cantharidae, 1856 (1815),
      Cerophytidae Latreille, 1834, Elateridae Leach 1815, Eucnemidae Eschscholtz,
      1829, Lampyridae Rafinesque, 1815, Lycidae Laporte, 1836, Phengodidae LeConte,
      1861 and Rhinorhipidae Lawrence, 1988. This catalogue includes type material of
      166 species distributed in 69 genera. Among 1,223 type specimens, are 86
      holotypes, 1,133 paratypes, 2 allotypes, 1 lectotype and 1 paralectotype. 

PMID- 25947472
TI  - The Peruvian Amazonian species of Epirhyssa Cresson (Hymenoptera: Ichneumonidae:
      Rhyssinae), with notes on tropical species richness.
AB  - Epirhyssa Cresson 1865 is a large tropical genus of the family Ichneumonidae. It
      is the most diverse genus of the subfamily Rhyssinae with about 118 species
      worldwide. In this study we conducted four long-term field inventories to review
      the Peruvian Amazonian species of the genus. We provide illustrations, diagnosis
      and an identification key to the species currently known to occur in the region,
      including descriptions of 10 new species. In addition, we describe the female of
      E. wisei Porter and the male of E. pertenuis Porter, discuss the biogeographical
      patterns of species richness of the genus and provide new faunistic records for
      Brazil, Colombia, Ecuador, French Guiana, Paraguay and Peru. The Peruvian
      Amazonia is, according to our results, among the most species-rich areas in the
      world for this genus. Some of the new species described in this work were named
      by the public in Finland and Peru during two innovative competitions to name
      these beautiful species. The aims of these competitions were to draw attention to
      the plethora of unknown species lurking in the shades of tropical forests and the
      necessity to protect these highly diverse areas. 

PMID- 25947473
TI  - The hypogean Iberian genus Typhlopsychrosoma Mauries, 1982 (Diplopoda,
      Chordeumatida, Vandeleumatidae): distribution map, key to species, first record
      in a Mesovoid Shallow Substratum (MSS) and detailed iconography of T. baeticaense
      (Mauries, 2013).
AB  - The troglobiont millipede Typhlopsychrosoma baeticaense (Mauries, 2013) is
      recorded in the Mesovoid Shallow Substratum (MSS) of two screes in the Aitana and
      Bernia mountains (Eastern Iberian Peninsula), far away from its known
      distribution area. A detailed Scanning Electron Microscopy iconography provides
      additional information on gonopod morphology, as well as other details such as
      the inconspicuous evaginations of the cuticle at the place of the eyes in the
      anophthalmous specimens. We present an updated distribution map and a key to
      species of the genus, with illustrations of the gonopods of all species described
      so far. The implications of the appearance of this hypogean species in an MSS are
      discussed. 

PMID- 25947474
TI  - Scyliorhinus ugoi, a new species of catshark from Brazil (Chondrichthyes:
      Carcharhiniformes: Scyliorhinidae).
AB  - A new species of catshark (Carcharhiniformes, Scyliorhinidae), Scyliorhinus ugoi
      sp. nov., is described from off Northeastern and Southeastern Brazil. The new
      species is closest to the Scyliorhinus haeckelii/besnardi group and S. hesperius
      but differs in background coloration, head width, sexual maturity, and in cranial
      and body proportions. 

PMID- 25947475
TI  - Two new species, Caenanthura koreana sp. nov. and Apanthura koreaensis sp. nov.
      (Crustacea: Isopoda: Anthuridae) from South Korea.
AB  - Two new species of anthuroid isopods, Caenanthura koreana sp. nov. and Apanthura
      koreaensis sp. nov. are described from the southern and western coasts of the
      Korean Peninsula. A key to the species and the type locality of Caenanthura are
      provided. Additionally, we determined the partial sequences of the mitochondrial
      cytochrome c oxidase subunit 1 (CO1) from two new species. 

PMID- 25947477
TI  - Description of two new species of the genus Stenothemus from Taiwan (Coleoptera:
      Cantharidae).
AB  - Two new species of the genus Stenothemus Bourgeois are described from Taiwan,
      under the names of S. seediq sp. nov. and S. cou sp. nov. Both species are
      provided with photos of habitus and illustrations of aedeagi, the seventh
      abdominal ventrites of females, and a distribution map for both the new species
      is presented. A key for the identification of Stenothemus species from Taiwan is
      given. 

PMID- 25947476
TI  - A new species of the genus Pareiorhina (Teleostei: Siluriformes: Loricariidae)
      from the upper rio Parana basin, southeastern Brazil.
AB  - Pareiorhina pelicicei sp. n., a new Loricariidae, is described from the rio
      Grande, upper rio Parana basin, southeastern Brazil. The new species differs from
      its congeners by combination of the following characters: teeth with a minute
      lateral cusp; absence of small plates scattered on the thorax and abdomen; tip of
      the snout naked; lower predorsal length; higher number of premaxillary and
      dentary teeth. 

PMID- 25947478
TI  - A new troglobitic species of the genus Pholeuonopsis (Coleoptera: Leiodidae:
      Cholevinae: Leptodirini) from western Serbia, with a key to the species from
      Serbia.
AB  - A new leptodirine leiodid beetle species, Pholeuonopsis (Pholeuonopsis)
      sljivovicensis sp. n., from a cave in western Serbia is described and diagnosed.
      The views of both male and female genitalia and other taxonomically important
      characters are imaged. The new species is clearly distinct from the closest
      relatives. It probably belongs to an old phyletic lineage of Mesogeid origin,
      like other known Pholeuonopsis taxa from the western part of the Balkan
      Peninsula. The new species is both an endemic and a relict inhabiting solely
      western Serbia. Morphological comparisons among the Serbian Pholeuonopsis species
      are provided, together with a key to the species. The genus Serbopholeuonopsis B.
      Curcic & Boskova, 2002 is regarded as a junior synonym of the genus Pholeuonopsis
      Apfelbeck, 1901. 

PMID- 25947479
TI  - Mantidflies of Colombia (Neuroptera, Mantispidae).
AB  - This study revises the Mantispidae of Colombia. 151 adult specimens of 12
      entomological museums of Colombia were examined and identified. On the basis of
      the specimens studied and a comprehensive literature search, it is determined
      that 20 nominal species (including two doubtful records) plus four proposed as
      new to science, in ten genera (Anchieta, Plega, Trichoscelia, Gerstaeckerella,
      Buyda, Climaciella, Dicromantispa, Entanoneura, Leptomantispa, and Zeugomantispa)
      and, three subfamilies (Symphrasinae, Drepanicinae, and Mantispinae) occur in
      Colombia. In addition, A. eurydella (Westwood), C. amapaensis Penny and P.
      fasciatella (Westwood) are redescribed, providing complementary information to
      the original descriptions. A list of Colombian Mantispidae, distribution maps and
      taxonomic keys to subfamilies, genera and species are included. Illustrations of
      the external morphology and male genitalia are provided for selected species. The
      taxonomic status of P. hagenella (Westwood) is discussed, and its diagnostic
      characters are redefined. Anchieta remipes (Gerstaecker) is newly transferred to
      this genus from Trichoscelia. 

PMID- 25947480
TI  - Gomphocythere besni n. sp. (Crustacea, Ostracoda) from a man-made pool (Adiyaman,
      Turkey).
AB  - We describe a new species (Gomphocythere besni n. sp.) from the Tavas man-made
      pool in Besni town (Adiyaman, Turkey). The species has several differences from
      its congeners in furcal structures (forked organ, seta of caudal ramus), numbers
      of setae on maxillula and maxillular palp, particular ornamentation with up to
      eight fossae in each mesh of the reticulation and in the presence of two types of
      lateral pore-canals (single pore opening with a sensillum and sieve plates) on
      the carapace. The finding of the new species extends the known geographical
      distribution of the living forms of the genus further to the North. The new
      species was found from relatively cool (16.6 oC) and medium oxygenated waters
      (7.36 mg/L) in a mixture of sand and gravel substrate. Details about its ecology
      and taxonomic status are also compared and discussed with other species of the
      same genus. 

PMID- 25947481
TI  - Checklist of the helminth parasites of South American bats.
AB  - Although the Chiroptera represents a significant proportion (c.20%) of the
      mammalian fauna and South America has the highest diversity of bat species, only
      about a third of the known species in this region have had helminth parasites
      reported from them. This work represents the first comprehensive checklist of the
      helminth parasites (nematodes, acanthocephalans, trematodes and cestodes) of
      South American bats. The data were extracted from more than 120 references and
      are presented as a key to each group of parasites down to the generic level, with
      an indication of how the bats become infected, accompanied by a list of the
      species recorded for each genus. This is followed, in tabular form, by parasite
      host and host-parasite checklists. The parasite-host list also includes their
      geographical distribution in South America (at the country level) and site data,
      plus the references in which the parasite records occur. The host-parasite list
      is arranged according to the classification of the hosts. In all, c.370 host
      parasite associations are recorded, involving 114 nominal species of helminths
      from 92 named chiropteran taxa. 

PMID- 25947483
TI  - A new species of the hermit crab genus Paguristes Dana, 1851 (Crustacea:
      Decapoda: Anomura: Diogenidae) from southwestern India.
AB  - A new species of the hermit crab genus Paguristes Dana, 1851 (Diogenidae), P.
      luculentus, is described and illustrated on the basis of three male specimens
      collected from off the Kerala State, southwestern India. It belongs to the
      species group characterized by the posterior lobes of the telson unarmed on the
      terminal margins, but the characteristic armature of the chelae and carpi of the
      chelipeds, consisting of a covering of numerous small corneous-tipped spines, and
      the presence of numerous small corneous-tipped or corneous spines on the mesial
      faces of the dactyli of the second pereopods immediately distinguish the new
      species from other congeneric species. The new species represents the ninth of
      the genus known from Indian waters. 

PMID- 25947482
TI  - Morphology of spermathecae of some pentatomids (Hemiptera: Heteroptera:
      Pentatomidae) from Turkey.
AB  - The spermathecal morphology of nine species belonging to the Pentatomidae
      (Insecta: Heteroptera) were compared by optical and scanning electron microscopy
      (SEM). Among the examined species [Rhaphigaster nebulosa (Poda 1761), Palomena
      prasina (Linnaeus 1761), Piezodorus lituratus (Fabricius 1794), Graphosoma
      lineatum (Linnaeus 1758), Graphosoma semipunctatum (Fabricius 1775), Aelia
      albovittata (Fieber 1868), Codophila varia (Fabricius 1787), Ancyrosoma
      leucogrammes (Gmelin 1790), Nezara viridula (Linnaeus 1758)], all spermathecae
      contained a spermathecal bulb (reservoir), a pumping region, distal and proximal
      flanges, proximal and distal spermathecal ducts, dilation of spermathecal duct
      and a genital chamber containing two ring sclerites, but each species had a
      different spermathecal morphology. 

PMID- 25947484
TI  - Oscheius onirici sp. n. (Nematoda: Rhabditidae): a new entomopathogenic nematode
      from an Italian cave.
AB  - Oscheius onirici sp. n. (Nematoda: Rhabditidae) was isolated from a karst cave
      soil of Central Italy. Molecular and morphological analyses were performed. Total
      DNA was extracted from individual nematodes and the mitochondrial COI, the ITS
      containing region, the D2-D3 expansion domains of the 28S rRNA gene and the 18S
      rRNA gene were amplified and sequenced. BLAST search at NCBI by using all
      molecular markers revealed that this taxon is similar to Oscheius species.
      Phylogenetic trees of ITS, 28S and 18S rDNA revealed that O. onirici sp. n.
      belongs to Dolichura-group. Oscheius onirici sp. n. is characterized by small
      body size and stoma rhabditoid type. Female reproductive system is amphidelphic.
      Males are rare with peloderan bursa, spicules slender and small, nine pairs of
      papillae of different lengths, arranged in a 1+1+1/3+3 pattern.
      Entomopathogenicity bioassay revealed that this nematode is capable of infecting
      larvae of Galleria mellonella and Tenebrio molitor. 

PMID- 25947485
TI  - Complete morphological re-description of mud-dwelling axiid Leonardsaxius
      amurensis (Kobjakova, 1937) with remarks on Axiidae (Crustacea: Decapoda:
      Axiidea) from the Russian coast of the Sea of Japan.
AB  - The first complete re-description of mud-dwelling axiid Leonardsaxius amurensis
      (Kobjakova, 1937) (Crustacea: Decapoda: Axiidea) is presented based on the
      holotype and freshly collected specimens from Vostok Bay, Russia coast of the Sea
      of Japan. The species is mostly morphologically similar to Leonardsaxius
      spinulicauda (Rathbun, 1902) known from Pacific coasts of North America from
      Vancouver to California but can be morphologically separated mainly by morphology
      of carapace and coloration of cornea of eyes. Remarks on distribution of
      Leonardsaxius amurensis (Kobjakova, 1937) and the second axiid species, Boasaxius
      princeps (Boas, 1880), known along Russian coastline of the Sea of Japan are
      given. 

PMID- 25947486
TI  - A new species and a new record of Trischistoma Cobb, 1913 (Nematoda: Enoplida:
      Trischistomatidae) from Shanxi Province, China.
AB  - This paper describes a new species and gives a new record and a re-description of
      a known species of Trischistoma Cobb, 1913. Trischistoma taiguensis sp. nov. is
      characterized by having one pair of caudal setae on the tail; female body length
      of 562-699 um, a = 35-42, b = 4.1-4.7, c = 11-14, c' = 3.9-4.6 and V = 79-82%.
      For the first time, Trischistoma pellucidum Cobb, 1913 is recorded from Shanxi
      Province, China. The phylogenetic relationships among species in the genus
      Trischistoma were analyzed using data from the SSU (small subunit) and D2/D3
      expansion segments of the LSU (large subunit) rDNA sequences. These analyses
      confirmed that T. taiguensis sp. nov. and T. pellucidum differ from other known
      members of the genus for which sequences are available in GenBank.

PMID- 25947487
TI  - An updated review of the genus Martensopoda Jager, 2006 (Araneae: Sparassidae:
      Heteropodinae).
AB  - A new species of the huntsman spider genus Martensopoda Jager, 2006, M. sanctor
      sp. nov., is described and illustrated from the southern Western Ghats of India.
      Detailed first description and illustration of the male of M. minuscula
      (Reimoser, 1934) with a redescription and illustration of its female are
      provided. The female of M. transversa Jager, 2006 is redescribed and illustrated.
      An identification key and a distribution map of all three Martensopoda species
      are presented. 

PMID- 25947488
TI  - New species of Microcentrum Scudder, 1862 (Orthoptera: Tettigonioidea:
      Phaneropteridae) from Amazon rainforest.
AB  - A regional study is performed for the Amazonian species of the genus Microcentrum
      Scudder, 1862, its proposed Microcentrum punctifrons Brunner von Wattenwyl, 1891
      as nomen dubium n. stat. and two new species are described: Microcentrum
      amacayacu Cadena-Castenada, Sovano n. sp. and Microcentrum xavieri Sovano, Cadena
      Castenada n. sp. the Colombian and Brazilian Amazon, respectively. A list and a
      key to the Amazonian species are also provided, along with a discussion on their
      distribution, according to endemism areas established to Amazon rainforest. 

PMID- 25947489
TI  - Genera of euophryine jumping spiders (Araneae: Salticidae), with a combined
      molecular-morphological phylogeny.
AB  - Morphological traits of euophryine jumping spiders were studied to clarify
      generic limits in the Euophryinae and to permit phylogenetic classification of
      genera lacking molecular data. One hundred and eight genera are recognized within
      the subfamily. Euophryine generic groups and the delimitation of some genera are
      reviewed in detail. In order to explore the effect of adding formal morphological
      data to previous molecular phylogenetic studies, and to find morphological
      synapomorphies, eighty-two morphological characters were scored for 203
      euophryine species and seven outgroup species. The morphological dataset does not
      perform as well as the molecular dataset (genes 28S, Actin 5C; 16S-ND1, COI) in
      resolving the phylogeny of Euophryinae, probably because of frequent convergence
      and reversal. The formal morphological data were mapped on the phylogeny in order
      to seek synapomorphies, in hopes of extending the phylogeny to include taxa for
      which molecular data are not available. Because of homoplasy, few globally
      applicable morphological synapomorphies for euophryine clades were found.
      However, synapomorphies that are unique locally in subclades still help to
      delimit euophryine generic groups and genera. The following synonyms of
      euophryine genera are proposed: Maeotella with Anasaitis; Dinattus with
      Corythalia; Paradecta with Compsodecta; Cobanus, Chloridusa and Wallaba with
      Sidusa; Tariona with Mopiopia; Nebridia with Amphidraus; Asaphobelis and Siloca
      with Coryphasia; Ocnotelus with Semnolius; Palpelius with Pristobaeus; Junxattus
      with Laufeia; Donoessus with Colyttus; Nicylla, Pselcis and Thianitara with
      Thiania. The new genus Saphrys is erected for misplaced species from southern
      South America.

PMID- 25947490
TI  - The Amazonian Goblin Spiders of the New Genus Gradunguloonops (Araneae:
      Oonopidae).
AB  - A new genus of soft-bodied oonopids, Gradunguloonops, is established for a group
      of goblin spiders found in the Amazonian rainforests of northern South America.
      Members of this genus differ from other oonopids in that the proclaw of tarsi I
      and II is notably larger than the corresponding retroclaw, a putative
      synapomorphy of the group. Gradunguloonops comprises twelve species, all new and
      described in this contribution: G. mutum (type species) from Brazil and Peru, G.
      bonaldoi, G. amazonicus, G. urucu, G. pacanari, G. juruti from Brazil, G. erwini
      from Peru, G. orellana and G. nadineae from Ecuador, G. benavidesae and G.
      florezi from Colombia, and G. raptor from Venezuela. Two preliminary intrageneric
      groups are proposed on the basis of their female genital morphology: the bonaldoi
      group, to which are assigned the species with the anterior section comprising
      only a single anterior sclerite, and the mutum group, with a more complex,
      tripartite anterior section.

PMID- 25947491
TI  - The recent apple snails of Africa and Asia (Mollusca: Gastropoda: Ampullariidae:
      Afropomus, Forbesopomus, Lanistes, Pila, Saulea): a nomenclatural and type
      catalogue. The apple snails of the Americas: addenda and corrigenda.
AB  - Ampullariidae are freshwater snails predominantly distributed in humid tropical
      and sub-tropical habitats in Africa, South and Central America and Asia. This
      catalogue is concerned only with the non-fossil Old World species, the majority
      of which are placed in the genera Pila and Lanistes, with a few species in
      Afropomus, Forbesopomus and Saulea. Pila occurs in Africa and Asia, Lanistes,
      Afropomus and Saulea only in Africa and Forbesopomus only in Asia. New World taxa
      were catalogued in a previous publication. The taxonomy of the group is heavily
      based on shell morphology but the true number of valid taxa remains unknown,
      pending revisionary work. This catalogue provides the rigorous nomenclatural base
      for this future work by bringing together all the available and unavailable genus
      group and species-group names that have been applied to Recent Asian and African
      ampullariids, indicating their current nomenclatural status (species, subspecies,
      synonyms, etc.). Fossil taxa are not included. The catalogue lists 21 published
      genus-group and 244 published species-group names of Old World ampullariids,
      excluding 25 names that are incertae sedis and cannot be definitively determined
      as Old or New World. Of these 265 Old World names, five genus-group and 104
      species-group (including 30 infraspecific) names are currently valid. There are
      16 genus-group synonyms, 118 species-group synonyms and four species-group
      homonyms that are not treated as junior synonyms. Also listed are five
      unavailable family-group, one unavailable genus-group and 18 unavailable species
      group names, and a number of unpublished names from museum labels. The catalogue
      provides bibliographic details for all published names, locations of type
      material, details of type localities and geographic distributions as far as can
      be ascertained given the confused state of the taxonomy. The catalogue is a work
      of nomenclature; it is not a revisionary work of taxonomy. Additional details and
      corrections to the earlier catalogue of the apple snails of the Americas are
      provided. No new names are proposed. Seven apparently new combinations are
      introduced, all with the genus Pila Preston: complicata Reeve, dira Reeve, major
      Germain (described as a variety of ovata Olivier), major Germain (described as a
      variety of speciosa Philippi), obvia Mabille, pallens Philippi, turbinoides
      Reeve.

PMID- 25947492
TI  - An updated checklist of Thyatirinae (Lepidoptera, Drepanidae) from China, with
      descriptions of one new species.
AB  - A total of three tribes, 38 genera and 148 species of Thyatirinae from China are
      listed together with one dubious record. Of these, one new species, Stenopsestis
      bruna sp. nov., is described. Macrothyatira danieli Werny, 1966, stat. rev., is
      restored to specific rank. Cymatophora subampliata Houlbert, 1921, is downgraded
      to subspecific rank as Tethea (Tethea) albicostata subampliata (Houlbert, 1921),
      stat. nov. Two genera, four species and three subspecies are recorded for the
      first time from China (Chiropsestis Laszlo, Ronkay & Ronkay, 2001, Hiroshia
      Laszlo, Ronkay & Ronkay, 2001, Chiropsestis rubrocinerea Laszlo, Ronkay & Ronkay,
      2001, Hiroshia albinigra Laszlo, Ronkay & Ronkay, 2001, Parapsestis hausmanni
      Laszlo, Ronkay, Ronkay & Witt, 2007, Spica luteola Swinhoe, 1889, Parapsestis
      cinerea pacifica Laszlo, Ronkay, Ronkay & Witt, 2007, Tethea (Saronaga)
      consimilis aurisigna Bryk, 1943, Nothoploca nigripunctata fansipana Laszlo,
      Ronkay & Ronkay, 2001). Ten misidentifications in Zhao (2004) are corrected.
      Illustrations of external features and genitalia of the new taxa and new records
      are presented. 

PMID- 25947493
TI  - A review of the finless snake eels of the genus Apterichtus (Anguilliformes:
      Ophichthidae), with the description of five new species.
AB  - The 18 species of finless snake eels of the genus Apterichtus (family
      Ophichthidae, subfamily Ophichthinae) are reviewed. Included are: A. anguiformis
      from the Mediterranean and eastern Atlantic; A. ansp from the Carolinas to Brazil
      in the western Atlantic; A. australis from South and Central Pacific islands,
      including Japan; A. caecus from the Mediterranean and eastern Atlantic; A.
      equatorialis from the eastern Pacific; A. flavicaudus from Hawaii, Midway Island,
      and possibly Australia and Seychelles; A. gracilis from the eastern central
      Atlantic; A. hatookai from Japan and China; A. kendalli from the western Atlantic
      and St. Helena Island; A. klazingai from South Africa to Hawaii; A. monodi from
      the eastern Atlantic; A. moseri from Japan; and A. orientalis from Japan. Five
      new species are described and illustrated: A. dunalailai from Vanuatu and Fiji at
      291-450 m; A. jeffwilliamsi from Vanuatu at 4-16 m; A. malabar from New South
      Wales, Australia at 44-66 m; A. mysi from the Marquesas Islands at 35-64 m; and
      A. nariculus from Ambon Island, Indonesia at 28-30 m. A neotype is designated for
      Apterichtus caecus. An identification key is provided. The synonymy of the genus
      Apterichtus is reviewed. Apterichtus keramanus Machida, Hashimoto & Yamakawa
      1997, is referred to ----------------Ichthyapus. 

PMID- 25947494
TI  - Additional notes on biting midges from the subtropical forest of northeastern
      Argentina (Diptera: Ceratopogonidae).
AB  - Adult males and pupae of Culicoides guarani Ronderos & Spinelli and Parabezzia
      brasiliensis Spinelli & Grogan are fully described and illustrated with a modern
      criterium from material recently collected in the vicinities of the city of
      Posadas in Misiones province, Argentina. Both species are compared with their
      most similar congeners. Besides, Bezzia blantoni Spinelli & Wirth and B.
      brevicornis (Kieffer) are firstly recorded from Misiones province. 

PMID- 25947495
TI  - Molecular systematics of the fishfly genus Anachauliodes Kimmins, 1954
      (Megaloptera: Corydalidae: Chauliodinae).
AB  - The fishfly genus Anachauliodes Kimmins, 1954 is endemic to the Oriental region
      and currently includes two species, Anachauliodes tonkinicus Kimmins, 1954 and A.
      sinensis Yang & Yang, 1992. These species are similar morphologically. We
      sequenced three mitochondrial genes: COI, ND2 and 16S rRNA in order to clarify
      the specific identity of these two species. Our results do not support the
      separation of these two species. We were also not able to find any morphological
      characters during comparison of Anachauliodes specimens from various localities
      useful in distinguishing these two species. Based on these results, we synonymize
      A. tonkinicus and A. sinensis and recognize A. laboissierei (Navas, 1913), comb.
      nov. & stat. rev. as the only valid species of Anachauliodes. 

PMID- 25947496
TI  - New Podoscirtine crickets (Orthoptera: Gryllidae; Podoscirtinae) from National
      Natural Park Amacayacu, Amazonas, Colombia.
AB  - We describe six new species of crickets from the subfamily Podoscirtinae in the
      family Gryllidae from the "Amacayacu" National Park: Diatrypa (Latispeculum)
      didieri n. sp. (Aphonoidini: Diatrypina), Ectotrypa brachyptera n. sp.
      (Paroecanthini: Paroecanthina), Aphonomorphus (Aphonomorphus) desutterae n. sp.,
      Aphonomorphus (Euaphonus) andreae n. sp., Aphonomorphus (Euaphonus) gorochovi n.
      sp., and Aphonomorphus (Nigraphonus) otavoi n. sp. (Podoscirtini:
      Aphonomorphina). Nigraphonus n. subgen. is proposed as a new subgenus of
      Aphonomorphus, grouping the species with unclear position into Neoaphonus (A.
      obscurus Chopard, 1956 n. comb., A. parobscurus Gorochov, 2010 n. comb., and A.
      nigra n. sp.). The state of knowledge of Podoscirtinae in Colombia is discussed. 

PMID- 25947497
TI  - A new species of anchovy, Encrasicholina macrocephala (Clupeiformes:
      Engraulidae), from the northwestern Indian Ocean.
AB  - A new species of anchovy, Encrasicholina macrocephala, is described on the basis
      of 17 specimens collected from the Red Sea and the Arabian Sea. The species is
      closely related to E. devisi in that both species have three unbranched rays in
      the dorsal and anal fins, and a long upper jaw (posterior tip extending beyond
      posterior margin of preopercle). However, the new species is distinguished from
      E. devisi in having lower counts of total pectoral-fin rays (11-14 vs. 13-15) and
      pseudobranchial filaments (15-18 vs. 18-22), longer head length (29.5-31.7% of
      standard length vs. 25.4-28.9% in the latter), upper-jaw length (21.3-23.5% vs.
      14.6-21.3%), and lower-jaw length (19.5-21.2% vs. 14.2-19.5%), and a shorter
      distance between the dorsal-fin origin to the pectoral-fin insertion (83.2-95.2%
      of head length vs. 97.6-126.1%). 

PMID- 25947498
TI  - The classification of Flabellochromus and Dumbrellia (Coleoptera: Lycidae) with
      descriptions of two new species of Calochromus from the Sundaland Region.
AB  - The adults of Calochromini with male flabellate antennae were studied. Two new
      Calochromus Guerin-Meneville, 1833 species with flabellate antennae, C.
      kelantanensis spec. nov. and C. harauensis spec. nov. are described. Dumbrellia
      Lea, 1909 (Calochromini) is proposed as a new junior synonym of Plateros
      Bourgeois, 1879 (Lycinae: Platerodini). Flabellochromus Pic, 1925 is transferred
      to Calochromus from synonymy with Dumbrellia based on the similar shape of the
      pronotum. Consequently, Calochromus lamellatus Kleine, 1926, comb. nov. from
      Sarawak and Flabellochromus pallidus Pic, 1925, comb. nov. (=Calochromus
      (Flabellochromus) pallidus Pic, 1925) from Luzon are returned to Calochromus. New
      combinations are proposed for three Australian species previously classified in
      Dumbrellia: Plateros brevicornis (Lea, 1898), comb. nov. (=Calochromus
      brevicornis Lea, 1898), P. pilosicornis (Lea, 1898), comb. nov. (=C. pilosicornis
      Lea, 1898) and P. melancholica (Lea, 1921), comb. nov. Plateros barronensis nom.
      nov. is proposed to replace Plateros pilosicornis (Lea, 1898), a junior secondary
      homonym of P. pilosicornis (Blanchard, 1853) (=Lycus pilosicornis Blanchard,
      1853). 

PMID- 25947499
TI  - Redescription of the females of Hystrignathus rigidus Leidy, 1850 (Nematoda:
      Hystrignathidae), parasites of Odontotaenius disjunctus (Coleoptera: Passalidae)
      from eastern USA.
AB  - The female of Hystrignathus rigidus Leidy, 1850 (Nematoda: Hystrignathidae) is
      redescribed on the basis of new material from Odontotaenius disjunctus
      (Coleoptera: Passalidae) from Athens, Georgia, USA; which also constitutes a new
      locality record. SEM images are provided for the first time for the species. It
      is also first shown that H. rigidus presents ridged-shelled eggs. A differential
      diagnosis is provided. H. rigidus can be differentiated from the rest of the
      species of this genus by having a short, non inflated first cephalic annule;
      spines that surpass the level of the oesophagus, an absence of lateral alae,
      ridged-shelled eggs and its length of the body and tail. The material from the
      present study differs from a previous redescription by Christie (1934) by its
      shorter body (2.125-2.950 vs. 2.130-4.200), first cephalic annule (0.003-0.005
      vs. 0.012) and oesophagus (0.350-0.430 vs. 0.650-0.670). 

PMID- 25947500
TI  - New species and reports of dactylogyrids (Monogenoidea) from Salminus
      franciscanus (Actinopterygii: Bryconidae) from the upper Sao Francisco River,
      Brazil.
AB  - Six species of dactylogyrid monogenoideans were collected at the upper Sao
      Francisco River, State of Minas Gerais, Brazil, from the gills of Salminus
      franciscanus. Anacanthorus adkruidenieri sp. n. and Anacanthorus paradouradensis
      sp. n. are described and compared with the other species of Anacanthorus.
      Anacanthorus adkruidenieri sp. n. is more similar to A. kruidenieri and A.
      parakruidenieri, but it can be distinguished from both by the rod-shaped
      accessory piece, which is articulated with the base of the male copulatory organ
      and is coiled around it, and by the shank of the hook, with expanded proximal
      bulbous portion bearing a central, elliptical foramen. Anacanthorus
      paradouradensis sp. n. resembles A. douradensis, but differs in the accessory
      piece, which is approximately half the length of the copulatory organ. Salminus
      franciscanus is a new host record and the Sao Francisco Basin is a new locality
      record for Anacanthorus daulometrus, Annulotrematoides glossophallus, Jainus
      iocensis and Tereancistrum arcuatus. 

PMID- 25947501
TI  - Leiostyla beatae n. sp. from eastern Georgia (Gastropoda: Lauriidae).
AB  - Leiostyla R.T. Lowe, 1852 is a disjunctly distributed pupilloid group of land
      snails known from the Macaronesian islands, Western Europe, Algeria, Bulgaria,
      Turkey, the Caucasus region and Iran (Pilsbry 1922-1923; Schileyko 1984;
      Gittenberger & Pieper 1988; Hausdorf 1990). In the Neogene the genus was more
      widespread in Central and Western Europe (Pilsbry 1922). Thus, the Caucasus
      region and the Macaronesian islands, where the highest recent diversity of
      Leiostyla species is found (Pilsbry 1922-1923), can be considered refugial areas.

PMID- 25947502
TI  - Two new synonyms among Chinese Thripinae (Thysanoptera: Thripidae).
AB  - Two species of Thripinae described from China, Danothrips dianellae Zhang and
      Tong, and Taeniothrips calopgomi Zhang, are here recognized as synonyms of two
      widespread Southeast Asian species. 

PMID- 25947503
TI  - Revision of the Neotropical subgenera Coelioxys (Platycoelioxys) Mitchell and C.
      (Rhinocoelioxys) Mitchell (Hymenoptera; Megachilidae) with the description of one
      new species.
AB  - Two Neotropical subgenera of Coelioxys Latreille are revised. The monotypic C.
      (Platycoelioxys) Mitchell and C. (Rhinocoelioxys) Mitchell has seven valid
      species; six of them (C. agilis Smith, C. barbata Schwarz & Michener, C.
      clypearis Friese, C. nasidens Friese, C. paraguayensis Schrottky and C. zapoteca
      Cresson) previously described, and one, C. platygnatha Rocha-Filho & Packer n.
      sp. is new from Amazonas State, Brazil. Coelioxys nasidens, previously considered
      a junior synonym of C. clypeata Smith, is resurrected. Coelioxys crassiceps
      Friese and C. excisa Friese are synonymized under C. agilis, and C. rostrata
      Friese is synonymized under C. paraguayensis. Nine names (C. clypeata, C.
      leucochrysea Cockerell, C. angustivalva Holmberg, C. doelloi Holmberg, C. blabera
      Holmberg, C. mesopotamica Holmberg, C. bilobata Friese, C. bilobata schenki
      Friese and C. bullaticeps Friese) are synonymized with C. zapoteca. In the latter
      species the shape of the apical margin of the clypeus of the female varies widely
      and, though intermediates occur among all forms, the DNA barcode sequences for
      the different forms are very similar. One species formerly considered as incertae
      sedis, C. clypearis, and one belonging to the subgenus C. (Cyrtocoelioxys)
      Mitchell, C. barbata, are both assigned to the subgenus C. (Rhinocoelioxys). Keys
      for both sexes of C. (Rhinocoelioxys), distribution maps, host and floral
      records, redescriptions of species and the description of a new species are
      provided. In the subgenus C. (Platycoelioxys), only one species, C. alatiformis
      Friese, is recognized with two junior synonyms: C. crassiceps Friese syn. nov.
      and C. spatuliventer Cockerell. 

PMID- 25947504
TI  - Systematics and faunistics of Neotropical Eucosmini. 1. Chimoptesis Powell, 1964
      (Lepidoptera: Tortricidae).
AB  - Twenty-one new species of Chimoptesis are described and illustrated: C.
      costaricae (TL: Costa Rica: San Jose), C. phanera (TL: Mexico: Chiapas), C.
      rubigo (TL: Mexico: Chiapas), C. rosariana (TL: Cuba: Pinar Rio), C. miniaula
      (TL: Mexico: Chiapas), C. kallion (TL: Mexico: Chiapas), C. potosiana (TL:
      Mexico: Nuevo Leon), C. obliquaria (TL: Mexico: Nuevo Leon), C. angulata (TL:
      Mexico: Chiapas), C. dentitia (TL: Mexico: Chiapas), C. faceta (TL: Mexico: Nuevo
      Leon), C. caera (TL: Mexico: Chiapas), C. castanescens (TL: Mexico: Chiapas), C.
      albomixta (TL: Mexico: Distrito Federal), C. cornigera (TL: Mexico: Nuevo Leon),
      C. mitrion (TL: Mexico: Nuevo Leon), C. setoses (TL: Cuba: Santiago), C.
      juniptesis (TL: Mexico: Chiapas), C. tamaulipasia (TL: Mexico: Tamaulipas), C.
      zoquiapana (Mexico: Distrito Federal), and C. rufobrunnea (TL: Costa Rica: San
      Jose). Formerly known only from the U.S., Chimoptesis is recorded south to Costa
      Rica in Central America and Cuba in the Caribbean. 

PMID- 25947505
TI  - Description of Pseudingolfiella possessionis n. sp. (Crustacea, Amphipoda) from
      sub-Antarctic Ile de La Possession, Crozet archipelago: the second freshwater
      amphipod known from the Antarctic biome, a human introduction of Gondwanan
      ancestry?
AB  - A new species of freshwater amphipod, Pseudingolfiella possessionis n. sp.
      (Senticaudata, Pseudingolfiellidae), is described from the submerged moss
      vegetation of small brooklets at sub-Antarctic Ile de La Possession, Crozet
      archipelago. It constitutes the second freshwater amphipod species known for the
      sub-Antarctic and Antarctic region, and the fourth member of the genus. The main
      characters distinguishing it from all congeners are: the spine on the posterior
      margin of the dactylus, incisor and lamina mobilis of mandible each with 5 teeth,
      the setation of the maxilliped, the vestigial second article of pleopod 3 in the
      female, the undulate and laterally notched posterolateral margin of the external
      ramus of uropods 1 and 2 in the male, the spinulate dorsomedian projection of the
      telson. 

PMID- 25947506
TI  - A new species of Cogia from Oaxaca, Mexico (Lepidoptera: Hesperiidae: Eudaminae).
AB  - A new species of Cogia A. Butler, 1870, is described from two localities ranging
      from 1470 to 2000 m elevation in the Sierra Madre del Sur of Oaxaca, Mexico; it
      occurs in cloud forest habitats and appears to be endemic to Mexico. Cogia buena,
      n. sp., is closely related to C. mala Evans, 1953 and C. aventinus (Godman &
      Salvin, 1894); these three species are the only known Cogia taxa whose males lack
      a hair tuft on the dorsal hindwing, and all have similar genitalia. 

PMID- 25947507
TI  - First record of the genus Neostatherotis Oku from China, with the descriptions of
      four new species (Lepidoptera: Tortricidae: Olethreutinae).
AB  - The tortricid genus Neostatherotis Oku, 1974 is newly reported from China, and
      four species are described as new: N. psilata, sp. nov., N. sparsula, sp. nov.,
      N. angustata, sp. nov., and N. breviuscula, sp. nov. Morphological descriptions
      and illustrations are provided, and a key for identification of the Chinese
      species is given. 

PMID- 25947508
TI  - A new species of soft-winged flower beetles of the genus Kuatunia Evers, 1945-48
      (Coleoptera, Cleroidea, Malachiidae) from Nepal.
AB  - A new malachiid species of the genus Kuatunia Evers is described: K. matthiasi
      sp. n., from Nepal, Seti Province; figures of male habitus, elytral appendices,
      genitalia, and a distribution map are presented. A determination key to all
      species of Kuatunia is also proposed. 

PMID- 25947509
TI  - Revision of the bryozoan genus Gephyrotes Norman, 1903 (Cheilostomata,
      Cribrilinidae) with the description of two new taxa.
AB  - The finding of a new species of Gephyrotes, G. moissettei n. sp., in Miocene
      deposits of southern Italy, prompted a revision of this distinctive cribrimorph
      taxon, leading to the redescription and first SEM documentation of the type
      material of nine species. Five of them are retained in Gephyrotes, namely the
      type species, G. nitidopunctatus, and G. fortunensis, G. spectabilis, G.
      quadriserialis, and G. convexus, to which G. moissettei n. sp. is added. The only
      Recent species is the genotype, while all the others are fossils from North
      America, Europe and northwest Africa. Two further species are transferred to the
      genus Tricephalopora, namely T. saillans and T. levigata, whereas Spiniflabellum
      n. gen., is established to accommodate a species from the Caribbean area, S.
      spinosum, previously assigned to Gephyrotes. 

PMID- 25947510
TI  - A new species of the Choroterpes Eaton, 1881 subgenus Monophyllus Kluge, 2012 and
      a new record of the subgenus Choroterpes, s.s. (Ephemeroptera: Leptophlebiidae)
      from southern Western Ghats, India.
AB  - A new species of Choroterpes (Monophyllus) is described based on larvae collected
      from rivers of Karnataka part of the Western Ghats. Choroterpes (Monophyllus)
      nandini n. sp. can be distinguished from the only other species viz., C.
      (Monophyllus) monophyllus by the following combination of characters: (i) median
      emargination of labrum moderately deep, without denticles; (ii) gills 2-7 without
      tracheation and (iii) abdominal segment 6 and 7 without colour pattern.
      Choroterpes (Choroterpes) petersi Tong and Dudgeon 2003 is newly recorded based
      on larval collections from the eastern and western regions of southern Western
      Ghats. 

PMID- 25947511
TI  - A new species of soft-winged flower beetles of the genus Platyebaeus Wittmer,
      1995 (Coleoptera, Cleroidea, Malachiidae) from Philippines.
AB  - A new malachiid species of the genus Platyebaeus Wittmer is described: P.
      quirinicus sp. n., from the Sierra Madre mountain range in Quirino province,
      Luzon Island, Philippines. Figures of male habitus, elytral apical third profile,
      genitalia, and a map showing the type locality are given for the new species. A
      determination key to the 3 species belonging to Platyebaeus is also provided. 

PMID- 25947512
TI  - Compositermes bani sp.n. (Isoptera, Termitidae, Apicotermitinae), a new species
      of soldierless termite from Bolivia.
AB  - Species of neotropical Apicotermitinae (Termitidae) are soldierless, restricting
      species identification in this group to workers or seasonally present winged
      imagos. All neotropical Apicotermitinae were placed in the genus Anoplotermes,
      until Mathews (1977) described two new genera, Grigiotermes and Ruptitermes.
      Fontes (1986) described two more genera, Aparatermes and Tetimatermes. Twenty
      years passed without any taxonomic advances in this group until Scheffrahn et al.
      2006 described two new Anoplotermes species from the West Indies and Bourguignon
      et al. 2010 described Longustitermes manni, (=Anoplotermes manni Snyder),
      Anoplotermes janus, and placed six other species into synonymy. Finally,
      Scheffrahn 2013 described a new genus and species, Compositermes vindai,
      characterized by a ring of sclerotized paddles at the junction of the enteric
      valve seating (EVS) and paunch (P3). 

PMID- 25947513
TI  - Taxonomic status of Engraulis nattereri Steindachner, 1880 (Osteichthyes:
      Clupeiformes: Engraulidae).
AB  - Engraulis nattereri Steindachner, 1880 was described on the basis of five
      specimens collected in Para during the Nathaniel Thayer Expedition. Later on, the
      species was assigned to Anchoviella by Fowler (1941). Including Anchoviella
      nattereri (Steindachner, 1880), Anchoviella comprises 17 small to medium-sized
      valid species (20-160 mm standard length), nine of them distributed in
      freshwaters of the Amazon, Essequibo, Corantijn and Orinoco river basins, and
      other eight brackish and marine species distributed along the Atlantic and
      Pacific coasts of North, Central and South America (Loeb & Figueiredo, 2014). 

PMID- 25947514
TI  - Taxonomy of the genus Ptomaphaginus Portevin (Coleoptera: Leiodidae: Cholevinae:
      Ptomaphagini) from China, with description of eleven new species.
AB  - Ptomaphaginus Portevin, 1914 is one of the most speciose genera in the tribe
      Ptomaphagini (Coleoptera: Leiodidae: Cholevinae). Its members are mainly soil
      dwellers and are almost all distributed in the Oriental Region. This paper
      reports eleven new species from China: P. guangxiensis sp. nov. (type locality:
      Napo, Guangxi autonomous region), P. gutianshanicus sp. nov. (type locality:
      Gutianshan, Zhejiang province), P. luoi sp. nov. (type locality: Shennongjia,
      Hubei province), P. newtoni sp. nov. (type locality: Wuzhishan, Hainan province),
      P. perreaui sp. nov. (type locality: Jinghong, Yunnan province), P.
      quadricalcarus sp. nov. (type locality: Xishuangbanna, Yunnan province), P.
      ruzickai sp. nov. (type locality: Baoxing, Sichuan province), P. shennongensis
      sp. nov. (type locality: Shennongjia, Hubei province), P. wenboi sp. nov. (type
      locality: Fushan, Taiwan province), P. wuzhishanicus sp. nov. (type locality:
      Wuzhishan, Hainan province) and P. yui sp. nov. (type locality: Lijiang, Yunnan
      province). Five other species known to occur in China were also reviewed and
      mostly redescribed to update the knowledge on their identification. The Chinese
      fauna of the genus Ptomaphaginus is thus increased to sixteen species. Important
      characters on the last two visible ventrites and aedeagus in the male as well as
      on the ventral side of the proleg are discussed, detailed line drawings are
      offered for each species, and a key to species from China is presented. 

PMID- 25947515
TI  - Taxonomic notes on the genus Anthaxia Eschscholtz, 1829 (Coleoptera: Buprestidae:
      Anthaxiini) 1.
AB  - In the present paper I propose the following taxonomic changes: Anthaxia
      (Haplanthaxia) bosdaghensis Obenberger, 1938 (= cavazzutii Bily, 1980 syn. nov.);
      A. (Anthaxia) ephippiata Redtenbacher, 1850 (= kreuzbergi Richter, 1944 syn.
      nov.); A. (H.) pleuralis Faimaire, 1883 (= parapleuralis Obenberger, 1929 syn.
      nov.); A. (H.) scylla Levey, 1985, removal from synonymy (= aprutiana Gerini,
      1955 unavailable name); A. (A.) truncata Abeille, 1900 (= lgockii Obenberger,
      1917 syn. nov.; = talyshensis Bily, 1991 syn. nov.; = adiyamana Svoboda, 1994
      syn. nov.). Lectotypes for A. (A.) kreuzbergi, A. (H.) parapleuralis and A. (A.)
      truncata are designated. All the studied types are illustrated, together with
      their original data labels. Each of the valid species is placed in its respective
      species-group, and notes are given on the distribution. 

PMID- 25947516
TI  - A review of species of the genus Apalochrus Erichson (Coleoptera, Malachiidae).
AB  - The genus Apalochrus Erichson, 1840 (Coleoptera, Cleroidea, Malachiidae) is
      revised. All seven species and subspecies of the genus have been discussed and
      described, all materials studied have been listed and the known distributions
      reported. Figures of male habiti, genitalia, and distribution map are supplied; a
      determination key is also provided. One new status and two new synonymies are
      proposed: A. femoralis pallipes Motschulsky, 1860 stat. n.; A. flavicornis
      Abeille de Perrin, 1890 = A. femoralis pallipes Motschulsky, 1860 syn. n. and A.
      notatus mongolicus Evers, 1968 = A. notatus (Zoubkoff, 1833) syn. n. 

PMID- 25947517
TI  - Synopsis of subfamily Haplogleniinae Newman, 1853 in China (Neuroptera:
      Ascalaphidae).
AB  - A synopsis of the subfamily Haplogleniinae Newman, 1853 (Neuroptera:
      Ascalaphidae) is presented. One new synonyms is proposed. Protidricerus
      palliventralis Yang, 1999 syn.n. is a junior synonym of Protidricerus elwesii
      (McLachlan, 1891). Two genera and eight species are redescribed and illustrated,
      and keys to the genera and species are presented. 

PMID- 25947518
TI  - The digger wasps of the genus Didineis Wesmael (Hymenoptera: Crabronidae:
      Bembicinae) of Russia and adjacent territories, with a key to species and new
      synonymies.
AB  - Ten species of Didineis Wesmael 1852 are recorded from Russia and adjacent
      territories. The new synonymy (valid name listed first) is established for
      Didineis bactriana Gussakovskij 1937 = D. ogloblini Gussakovskij 1937, D.
      clavimana Gussakovskij 1937 = D. turanica Gussakovskij 1937, and D. lunicornis
      (Fabricius 1798) = Didineis ruthenica Gussakovskij 1937. The number of valid
      species-group taxa in the genus Didineis is reduced to 25. The lectotypes are
      designated for four species: Didineis bactriana Gussakovskij 1937, D.
      botsharnikovi Gussakovskij 1937, D. clavimana Gussakovskij 1937, D. ruthenica
      Gussakovskij 1937. An original key to the species is provided. 

PMID- 25947519
TI  - A cultivable acoel species from the Mediterranean, Aphanostoma pisae sp. nov.
      (Acoela, Acoelomorpha).
AB  - Aphanostoma pisae sp. nov. is an interstitial acoel found at the coast of the
      Liguric Sea in Pisa (Tuscany, Italy). It belongs to the large family
      Isodiametridae, characterised by a male copulatory organ with a cylindrical shape
      and non-anastomising longitudinal muscle fibers. It is the first recognised
      species of Aphanostoma in the Mediterranean and it can occur in great abundance
      at its type locality (several hundred specimens in a spoonful of sand). A. pisae
      has been cultured in the laboratory for several years with diatoms for food. The
      embryonic development lasts for just under two days at 20  degrees C. We provide
      a description of the new species using live observations, light and electron
      microscopy of sagittal sections and stainings of the filamentous actin and the
      serotonergic nervous system, and we discuss and update the genus diagnoses of the
      genera Aphanostoma and Praeconvoluta. 

PMID- 25947520
TI  - Description of two new species of the genus Devadatta from northern Vietnam and
      central Laos (Odonata: Devadattidae).
AB  - Two new species of the genus Devadatta Kirby, 1890, D. kompieri sp. nov. from
      northern Vietnam (holotype: male, Mu Cang Chai district, Yen Bai Province) and D.
      yokoii sp. nov. from central Laos (holotype: male, Vang Vieng, Vientiane
      Province) are described. These new species are allied to D. ducatrix Lieftinck,
      1969, but are distinguished by specific characteristics of their wings and anal
      appendages. The other Indochinese species are also briefly discussed. 

PMID- 25947521
TI  - A new species of the ant-hunter genus Tracheliodes Morawitz (Hymenoptera:
      Crabronidae: Crabronini) from Brazil.
AB  - Tracheliodes leclercqi sp. n., a new species of the ant-hunter genus Tracheliodes
      Morawitz, is described from southeastern Brazil. It closely resembles T. cutucu
      Cooper, 1988 and the main differences between the two species are presented.
      Photographs of type specimens of T. leclercqi sp. n., as well as of a female and
      a male paratypes of T. cutucu, are provided. 

PMID- 25947522
TI  - Badis britzi, a new percomorph fish (Teleostei: Badidae) from the Western Ghats
      of India.
AB  - Badis britzi, the first species of the genus endemic to southern India, is
      described from the Nagodi tributary of the west-flowing Sharavati River in
      Karnataka. It is distinguished from congeners by a combination of characters
      including a slender body, 21-24 pored lateral-line scales and a striking colour
      pattern consisting of 11 bars and a mosaic of black and red pigmentation on the
      side of the body including the end of caudal peduncle, and the absence of
      cleithral, opercular, or caudal-peduncle blotches, or an ocellus on the caudal
      fin base. Badis triocellus Khynriam & Sen is considered a junior synonym of B.
      singenensis Geetakumari & Kadu. 

PMID- 25947523
TI  - Brazilian Histerini (Coleoptera, Histeridae, Histerinae): a new species, key to
      the genera, and checklist of species.
AB  - A new species of the Hister coenosus group from southern Brazil is described.
      Hister lucia sp. nov. is the largest Hister sp. in the New World, and is also
      distinguished by its dorsally and laterally concave mandibles. The three genera
      of Histerini recorded from Brazil are keyed, and a checklist of species of the
      tribe recorded from Brazil is presented. In total, seventeen described species of
      Histerini are recorded from Brazil, including fifteen of Hister Linnaeus, one of
      Atholus C. Thomson, and one of Margarinotus Marseul. 

PMID- 25947524
TI  - Afrostilobezzia, a new genus of predatory biting midges from the Afrotropical
      Region (Diptera: Ceratopogonidae).
AB  - A new genus Afrostilobezzia gen. nov. including A. clastrieri sp. nov. and A.
      ornatithorax (Clastrier, 1988) comb. nov. is described from West Africa (Nigeria
      and Guinea). 

PMID- 25947525
TI  - Opportunity in our Ignorance: Urban Biodiversity Study Reveals 30 New Species and
      One New Nearctic Record for Megaselia (Diptera: Phoridae) in Los Angeles
      (California, USA).
AB  - An urban biodiversity study sampling primarily from private backyards in Los
      Angeles, California (USA), reveals the presence of fifty-six species of Megaselia
      within the first few months of sampling. Thirty of these are described as new to
      science: M. armstrongorum, M. bradyi, M. brejchaorum, M. carthayensis, M.
      ciancii, M. creasoni, M. defibaughorum, M. donahuei, M. francoae, M. fujiokai, M.
      hardingorum, M. heini, M. hentschkeae, M. hoffmanorum, M. hoggorum, M. hoguei, M.
      isaacmajorum, M. kelleri, M. lombardorum, M. marquezi, M. mikejohnsoni, M.
      oxboroughae, M. pisanoi, M. renwickorum, M. rodriguezorum, M. sacatelensis, M.
      seaverorum, M. sidneyae, M. steptoeae, and M. wiegmanae. M. largifrontalis is
      newly reported from the Nearctic Region. The implications these findings have for
      future taxonomic work in Megaselia, particularly in urban areas, are discussed. 

PMID- 25947526
TI  - A new genus of Stenetriidae Hansen, 1905 (Asellota: Isopoda: Crustacea) from the
      Great Barrier Reef, Australia and the southwestern Pacific.
AB  - Onychatrium gen. nov. is described, with five included species: Onychatrium
      forceps sp. nov., the type species and Onychatrium torosus sp. nov., both from
      the Great Barrier Reef; Onychatrium entale (Nordenstam, 1946) comb. nov., from
      Tapateuen (= Tabiteue Island), Gilbert Islands; Onychatrium thomasi (Bolstad &
      Kensley, 1999) comb. nov., from Madang, Papua New Guinea; and Onychatrium
      echiurum (Nobili, 1906) comb. nov., and species inquirenda from the Tumaotu
      Islands, Eastern French Polynesia. The primary distinguishing characters for
      Onychatrium gen. nov. are a trapezoid pseudosrostrum, the male pereopod 1 with
      elongate dactylus (4.7-7.3 as long as proximal width), propodus with strongly
      produced and acute lobe, carpus with a distally acute, flat, ventrally directed
      process (except O. torosus sp. nov., which has a short and truncate process) and
      the merus with a distally directed inferodistal lobe. The genus is known only
      from the southern Pacific, from the Tuamotus (eastern French Polynesia) to the
      Great Barrier Reef and northern Papua New Guinea. 

PMID- 25947527
TI  - New taxa of Meconematini (Orthoptera: Tettigoniidae: Meconematinae) from Guangxi,
      China.
AB  - The following new taxa of Meconematini from Guangxi province were described:
      Sinothaumaspis damingshanicus Wang, Liu, Li gen. & sp. nov., Aphlugiolopsis
      punctipennis Wang, Liu, Li gen. & sp. nov., Eoxizicus (Eoxizicus) curvicercus
      Wang, Liu, Li sp. nov., Meconemopsis paraquadrinotata Wang, Liu, Li sp. nov.,
      Neocrytopsis? unicolor Wang, Liu, Li sp. nov., Xiphidiopsis (Dinoxiphidiopsis)
      expressa Wang, Liu, Li sp. nov. Xiphidiopsis (Xiphidiopsis) fischerwaldheimi
      Gorochov, 1993, a synonym of Xiphidiopsis (Xiphidiopsis) jinxiuensis Xia & Liu,
      1990 was described. The opposite gender of Sinocyrtaspis truncate Liu, 2000 and
      Abaxinicephora excellens Gorochov & Kang, 2005 were firstly described. 
      Xiphidiopsis (Dinoxiphidiopsis) jacobsoni Gorochov, 1993 was also firstly
      recorded from China. Two new combinations,  Meconemopsis quadrinotata (Bey
      Bienko, 1971) Wang, Liu, Li comb. nov. and Xiphidiopsis (Dinoxiphidiopsis)
      fanjingshanensis (Shi & Du, 2006) Wang, Liu, Li comb. nov., as well as a synonym
      of the former Xizicus (Axizicus) xizangensis Jiao & Shi 2013 syn. nov. which
      respectively relate to M. paraquadrinotata sp. nov. and X. (D.) expressa sp.
      nov., were also noted. 

PMID- 25947528
TI  - Two new tardigrade species from Romania (Eutardigrada: Milnesiidae,
      Macrobiotidae), with some remarks on secondary sex characters in Milnesium
      dornensis sp. nov.
AB  - In two moss and lichen samples collected in Romania, two new eutardigrade species
      were found. Milnesium dornensis sp. nov. belongs to the granulatum group and
      differs from most of other species in this group mainly by having a different
      claw configuration ([3-3]-[3-3]) and by some morphometric characters. Minibiotus
      diversus sp. nov. is very similar to M. gumersindoi Guil & Guidetti, 2005 and M.
      weglarskae Michalczyk et al., 2005, but differs from these and other congeners by
      the cuticular pore arrangement and morphometric characters of both adults and
      eggs. Males and females of the newly described Milnesium species differ not only
      by the shape and structure of claws I, but also by other morphometric characters.
      Males of Milnesium dornensis sp. nov. are smaller, more slender, have shorter
      papillae and relatively longer claws on legs III-IV. 

PMID- 25947529
TI  - New material of Longipteryx (Aves: Enantiornithes) from the Lower Cretaceous
      Yixian Formation of China with the first recognized avian tooth crenulations.
AB  - We report on a new specimen of Longipteryx chaoyangensis from the Lower
      Cretaceous Yixian Formation in Chaoyang, Liaoning Province, China. The new
      material preserves previously unknown tooth crenulations. This is the first
      recognized tooth crenulations within Aves. It not only provides new information
      regarding the anatomy of the Longipteryx, but also sheds new light on the trophic
      specialization of this genus and even this family. It was discovered from the
      Yixian Formation, which is older than the Longipteryx chaoyangensis bearing
      Jiufotang Formation. This new discovery also expands the known stratigraphic
      range of Longipteryx. 

PMID- 25947530
TI  - A new sea star of the genus Leptasterias (Asteroidea: Asteriidae) from the
      Aleutian Islands.
AB  - A new species of asteriid sea star of the genus Leptasterias (Order
      Forcipulatida) is described from the nearshore waters of the Aleutian Islands.
      Leptaterias tatei sp. nov. is distinguished from Leptasterias stolacantha Fisher,
      1930, by the characteristics of the spines and pedicellariae. Geographic
      distribution is discussed and a key to the five-rayed Leptasterias of the
      Aleutian Islands is provided. 

PMID- 25947531
TI  - On the identity of the tiger beetle Cicindela philippinensis Mandl, 1956
      (Coleoptera: Carabidae: Cicindelinae).
AB  - In the course of preparing a key to the Philippine tiger beetle genera
      (Pangantihon & Zettel, in prep.) it became necessary to examine the holotype of
      Cicindela philippinensis Mandl, 1956, the only specimen from the Philippines that
      has been tentatively assigned to the genus Myriochila Motschulsky, 1857. 

PMID- 25947532
TI  - A new species of Caenis Stephens, 1836 (Ephemeroptera: Caenidae) from Southern
      Brazil.
AB  - A new species of the genus Caenis Stephens is described based on the male imago,
      female imago and egg stages from the state of Rio Grande do Sul, Brazil. The male
      imago of Caenis gaucha sp. nov. is diagnosed as follows: body length of male 2.0
      2.5 mm; base of antennal flagellum not dilated; forceps apically rounded, not
      fused to lateral margins of styliger plate; styliger plate short with posterior
      margin slightly sub-triangular; ratio of foreleg 1.7-2.2 * the length of hind
      leg, forceps length 4.4-6.0 * the width 1/2 from base, and distance between the
      extreme lateral points of the forceps bases 1.7-1.8 * forceps length. 

PMID- 25947533
TI  - A family-group name correction in Aves: Tachurisidae instead of Tachurididae
      Ohlson, Irestedt, Ericson & Fjeldsa, 2013.
AB  - The genus Tachuris Lafresnaye, 1836 was recently placed in a new monotypic family
      rank taxon, Tachurididae Ohlson, Irestedt, Ericson & Fjeldsa, 2013, proposed to
      reflect the molecular recovery of this taxon as an independent lineage related to
      Tyrannidae Vigors, 1825 and Rhynchocyclidae Berlepsch, 1907 (Ohlson et al. 2013).
      The purpose of this paper is to propose a correction in the original spelling of
      the family name Tachurididae used by Ohlson et al. (2013) to agree with the
      rulings of the International Code of Zoological Nomenclature (ICZN 1999;
      hereafter "Code"), taking account of the complex etymology of the name. 

PMID- 25947534
TI  - The first record of Pyxidium tardigradum Van der Land, 1964 (Ciliophora) in
      Romania.
AB  - In three lichen samples collected from eastern part of Romania, three populations
      of Ramazzottius cf. oberhaeuseri (Doyere, 1840) infested by Pyxidium tardigradum
      Van der Land 1964 were found. In this short correspondence we present a first
      record of P. tardigradum in Romania and infestation rates in studied populations
      according to the different life stages. 

PMID- 25947535
TI  - NAERCIO A. MENEZES, MAURO NIRCHIO & CLAUDIO DE OLIVEIRA & RAQUEL SICCHARAMIREZ
      (2015). Taxonomic review of the species of Mugil (Teleostei: Perciformes:
      Mugilidae) from the Atlantic South Caribbean and South America, with integration
      of morphological, cytogenetic and molecular data.  Zootaxa, 3918 (1): 001-038.

PMID- 25947536
TI  - Small scale endemism in Brazil's Atlantic Forest: 14 new species of Mesabolivar
      (Araneae, Pholcidae), each known from a single locality.
AB  - In an ongoing mega-transect project that aims at analyzing pholcid spider
      diversity and distribution in the Atlantic Forest of Brazil, many species appear
      restricted to small geographic ranges. Of the 84 species collected between 2003
      and 2011 at 17 sites between Bahia and Santa Catarina, 51 species (61%) were
      found at only one locality. The present paper focuses on such species in the
      genus Mesabolivar, and compares diversity and distribution patterns of this genus
      within and outside the Atlantic Forest. The percentage of species known from
      single localities is higher in the Atlantic Forest (34 of 52 species; 65%) than
      outside the Atlantic Forest (10 of 25; 40%). Distribution rages of species in the
      Atlantic Forest are significantly smaller than of species outside the Atlantic
      Forest (mean maximum distances between localities: 184 versus 541 km; medians: 10
      km versus 220 km). The following species are newly described (arranged from north
      to south), each currently known from the respective type locality only: M.
      caipora; M. kathrinae; M. bonita; M. pau (Bahia); M. monteverde; M. perezi
      (Espirito Santo); M. giupponii; M. goitaca; M. sai (Rio de Janeiro); M. tamoio;
      M. unicornis; M. gabettae; M. inornatus (Sao Paulo); M. itapoa (Santa Catarina).

PMID- 25947537
TI  - A sea of worms: polychaete checklist of the Adriatic Sea.
AB  - The checklist of polychaetes of the Adriatic Sea (Mediterranean) based on
      bibliographic sources published from 1840 to 2014, as well as on novel data, with
      49 new records for the area, is herein presented. The Adriatic Sea polychaete
      fauna comprises at present of 764 species in 360 genera and 62 families. The
      richest family is the Syllidae, with 112 species (c.a. 15% of the all taxa).
      Eight families account for as much as 50% of the diversity (Syllidae, Serpulidae,
      Sabellidae, Phyllodocidae, Spionidae, Polynoidae, Terebellidae and Nereididae).
      Among the three Adriatic sectors (Northern, Central and Southern Adriatic), the
      Northern Adriatic is the richest one, whereas the composition of the most diverse
      families is very similar in all sectors. Data on endemisms (6), aliens (29) and
      valid species with the type locality in the Adriatic Sea (90) are also discussed.
      The list of all relevant papers citing each species in the Adriatic is included,
      allowing future detailed information retrievals for distinct purposes. Results
      suggest that the number of species will keep increasing in the future, as new
      surveys will be undertaken, so regular updates of the present list will be
      necessary.

PMID- 25947538
TI  - Brevipalpus phoenicis (Geijskes) species complex (Acari: Tenuipalpidae)--a closer
      look.
AB  - Brevipalpus phoenicis sensu stricto (Geijskes) is redescribed and the species
      diagnosis established. Two former synonyms of B. phoenicis sensu lato, B.
      yothersi Baker and B. papayensis Baker, are resurrected and redescribed and their
      species diagnoses established. Brevipalpus hondurani Evans is also redescribed
      and diagnosed. Four new species, previously misidentified as B. phoenicis sensu
      lato or B. obovatus Donnadieu, are described--B. azores sp. nov., B. feresi sp.
      nov., B. ferraguti sp. nov., and B. tucuman sp. nov. Four new junior synonyms of
      B. yothersi are listed--Brevipalpus amicus Chaudhri and B. recula Chaudhri (new
      synonymies), and B. mcbridei Baker and B. deleoni Pritchard and Baker
      (misidentifications). A key is provided to separate these species. New
      morphological characters significant for species separation are presented and
      discussed.

PMID- 25947539
TI  - Groundwater cyclopoid copepods of peninsular India, with description of eight new
      species.
AB  - To date, only three stygobiotic cyclopoid species are known from India:
      Haplocyclops (Kiefercyclops) fiersi Karanovic & Ranga Reddy, 2005 and Rybocyclops
      dussarti Ranga Reddy & Defaye, 2008, from bores, and Allocyclopina inopinata
      Defaye & Ranga Reddy, 2008, from brackish conditions of a hyporheic habitat.
      Analysis of numerous groundwater samples collected during 2008-2013 from the
      hyporheic and phreatic habitats in the coastal deltaic belt of the Rivers Krishna
      and Godavari in Andhra Pradesh state, southeastern India, has shown ten
      stygobiotic cyclopoid species, of which eight are new to science: Anzcyclops
      indicus n. sp., Brevicyclops asetosus n. g., n. sp., Brevicyclops brevisetosus n.
      g., n. sp., Brevicyclops viduus n. g., n. sp., Halicyclops martinezi n. sp.,
      Haplocyclops (Kiefercyclops) godavari n. sp., Haplocyclops (Kiefercyclops)
      primitivus n. sp., and Rybocyclops defayeae n. sp. All these species are formally
      described and illustrated herein. Allocyclopina inopinata, which perfectly agrees
      with its original account, is also recorded in several localities besides its
      type locality. The heretofore incompletely characterised Paracyclopina orientalis
      (Lindberg, 1941) is redescribed. A new cyclopid genus, Brevicyclops n. g., is
      established for three aforementioned new species. Its most diagnostic
      synapomorphy is the extreme reduction or complete absence of the principal outer
      apical seta of caudal ramus. So far, the cosmopolitan genus Halicyclops Norman,
      1903, is known by six species in India, all from the surface environments. Now, a
      new species, H. martinezi n. sp., is described from an interstitial hyporheic
      habitat, and an identification key given for all the Indian species. The genus
      Anzcyclops Karanovic, Eberhard & Murdoch, 2011, which has hitherto been known
      from the Western Australia and New Zealand, is discovered in this study. A new
      species, Anzcyclops indicus n. sp., which has a close relationship with its
      Western Australian congeners, is described. A brief note on the biogeography of
      the Indian stygobiotic crustaceans is also added.

PMID- 25947540
TI  - A pre-conditioning stress accelerates increases in mouse plasma inflammatory
      cytokines induced by stress.
AB  - BACKGROUND: Major depressive disorder is a prevalent disease that is inadequately
      treated with currently available interventions. Stress increases susceptibility
      to depression in patients and rodent models. Depression is also associated with
      aberrant activation of inflammation, such as increases in circulating levels of
      interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha (TNFalpha). The two
      main goals of this study were (i) to identify cytokine changes measuring a broad
      panel of 19 cytokines, and (ii) to test if a pre-conditioning stress altered the
      inflammatory response to a subsequent stress. RESULT: Stress-induced changes in
      mouse plasma cytokines were measured by multiplex following administration of one
      or two daily stresses of inescapable foot shocks using the learned helplessness
      paradigm for modeling depression-like behavior. Administration of inescapable
      foot shocks increased plasma levels of IL-1beta, IL-6, TNFalpha, IL-3, IL-10, IL
      13, IL-17A, IL-5, GM-CSF, IL-12(p70), IFN-gamma, MIP-1alpha, MIP-1beta, IL
      1alpha, IL-2, KC, RANTES and G-CSF, with peak levels occurring in the range of 6
      to 12 hr after stress. Pre-conditioning the mice 24 hr before with an equivalent
      inescapable foot shock stress resulted in similar magnitudes of increases in most
      cytokines as occurred after a single stress, but accelerated the increase,
      causing the levels of most cytokines to peak 1 hr after stress. These results
      demonstrate that a single stress induces the expression of many cytokines, and
      that sequential, daily stresses accelerates the rate of cytokine production.
      CONCLUSIONS: Acute stress broadly activates inflammation in mice, and the
      inflammatory response is more rapid following repeated stress, actions that may
      contribute to deleterious effects of stress on depression and other stress-linked
      diseases.

PMID- 25947542
TI  - Phosphorene as an anode material for Na-ion batteries: a first-principles study.
AB  - We systematically investigate a novel two-dimensional nanomaterial, phosphorene,
      as an anode for Na-ion batteries. Using first-principles calculations, we
      determine the Na adsorption energy, specific capacity and Na diffusion barriers
      on monolayer phosphorene. We examine the main trends in the electronic structure
      and mechanical properties as a function of Na concentration. We find a favorable
      Na-phosphorene interaction with a high theoretical Na storage capacity. We find
      that Na-phosphorene undergoes semiconductor-metal transition at high Na
      concentration. Our results show that Na diffusion on phosphorene is fast and
      anisotropic with an energy barrier of only 0.04 eV. Owing to its high capacity,
      good stability, excellent electrical conductivity and high Na mobility, monolayer
      phosphorene is a very promising anode material for Na-ion batteries. The
      calculated performance in terms of specific capacity and diffusion barriers is
      compared to other layered 2D electrode materials, such as graphene, MoS2, and
      polysilane. 

PMID- 25947543
TI  - Scaling up self-assembly: bottom-up approaches to macroscopic particle
      organization.
AB  - This review presents an overview of recent work in the field of non-Brownian
      particle self-assembly. Compared to nanoparticles that naturally self-assemble
      due to Brownian motion, larger, non-Brownian particles (d > 6 MUm) are less prone
      to autonomously organize into crystalline arrays. The tendency for particle
      systems to experience immobilization and kinetic arrest grows with particle
      radius. In order to overcome this kinetic limitation, some type of external
      driver must be applied to act as an artificial "thermalizing force" upon non
      Brownian particles, inducing particle motion and subsequent crystallization. Many
      groups have explored the use of various agitation methods to overcome the natural
      barriers preventing self-assembly to which non-Brownian particles are
      susceptible. The ability to create materials from a bottom-up approach with these
      characteristics would allow for precise control over their pore structure (size
      and distribution) and surface properties (topography, functionalization and
      area), resulting in improved regulation of key characteristics such as mechanical
      strength, diffusive properties, and possibly even photonic properties. This
      review will highlight these approaches, as well as discuss the potential impact
      of bottom-up macroscale particle assembly. The applications of such technology
      range from customizable and autonomously self-assembled niche microenvironments
      for drug delivery and tissue engineering to new acoustic dampening, battery, and
      filtration materials, among others. Additionally, crystals made from non-Brownian
      particles resemble naturally derived materials such as opals, zeolites, and
      biological tissue (i.e. bone, cartilage and lung), due to their high surface
      area, pore distribution, and tunable (multilevel) hierarchy. 

PMID- 25947541
TI  - Women's relative immunity to the socio-economic health gradient: artifact or
      real?
AB  - BACKGROUND: Individual and area socio-economic status (SES) are significant
      predictors of morbidity and mortality in developed and developing countries.
      However, the span in health from poorest to richest, that is, the socio-economic
      gradient, appears steeper for men than women. OBJECTIVE: Our aim is to understand
      women's apparent immunity to the health harms of the SES gradient. DESIGN:
      Findings from a non-systematic search of Medline for population-based, SES
      gradient studies reporting results for both men and women and with health
      outcomes of morbidity, mortality or self-rated health (SRH) were reflectively
      analyzed. RESULTS: The 36 papers reviewed generally showed women to be relatively
      immune to the SES gradient for all but cardiovascular health outcomes. However,
      addressing the interconnected nature of socio-economic circumstances, exploring
      whether some measures of SES had ambiguous meanings for either women or men,
      including modifiers of SES such as household circumstances, social capital or
      area gender equity, or using indicators of area SES that were contextual rather
      than aggregates of individual, compositional measures increased the SES gradient
      for women. Outcome measures that combined mental and physical health, accounted
      for gender differences in SRH and adjusted for sex-specific differences in causes
      of mortality also explained some of the observed amelioration of the SES gradient
      among women. CONCLUSIONS: Socio-economic circumstances have a real and sustained
      impact on individual health. The SES gradient appears stronger for men than for
      women for all health outcomes other than heart disease. However, some of the
      observed variability between men and women may be an artifact of biased
      methodology. Considering webs of causation rather than individual markers of SES
      along with other sources of gender bias can explain much of women's blunted socio
      economic gradient and deepen understanding of the pathways from SES to morbidity
      and mortality overall.

PMID- 25947544
TI  - Very early virological failure and drug resistance mutations in a woman on
      antiretroviral therapy in Eastern Cape, South Africa: a case report.
AB  - INTRODUCTION: Rapid scale-up of antiretroviral therapy rollout in Sub-Saharan
      African countries faces the challenge of virological failure. This could be the
      consequence of transmitted drug-resistant human immunodeficiency virus strains at
      the population level. While a pre-antiretroviral therapy genotypic test has been
      a major component of the human immunodeficiency virus management programme in
      developed nations, it is yet to be incorporated into the antiretroviral therapy
      programme in resource-poor countries. CASE PRESENTATION: A 32-year-old Black
      African woman was seen for her six-month routine review. Her viral load after
      initiation of fixed drug combination of tenofovir, emtricitabine and efavirenz
      was 31,397 RNA copies/mL. Adherence was assessed to be good based on pharmacy
      pick-up dates, on-time clinic appointment records, medical file review, self
      reporting and treatment supporter's report. Her viral load was repeated after
      another two months of close monitoring; the result showed viral load of 31,159
      RNA copies/mL. She was assessed as virological failure to her first-line
      antiretrovirals and commenced on second-line antiretrovirals:
      zidovudine/lamivudine/Aluvia((r)) (lopinavir and ritonavir). A human
      immunodeficiency virus drug genotypic testing showed she was only susceptible to
      zidovudine and protease inhibitors. At third month on the new regimen, her viral
      load was suppressed. CONCLUSIONS: This case report demonstrates the possibility
      of a silent epidemic within the human immunodeficiency virus pandemic in resource
      poor settings like Eastern Cape, South Africa. We described a case of early
      virological failure in a highly motivated young woman. Although, a pre
      antiretroviral therapy genotypic test is yet to be incorporated into a human
      immunodeficiency virus programme in resource-poor countries, the need for it
      might become evident as the programme expands. Close monitoring of the viral load
      of patients according to national guidelines will enable early detection of a
      failing regimen and prompt intervention can be instituted to prevent morbidity
      and mortality. There is an urgent need to strengthen the human immunodeficiency
      virus programme in resource-poor countries to prevent the emergence of an
      epidemic of transmitted drug-resistant human immunodeficiency virus strains
      within the existing human immunodeficiency virus pandemic.

PMID- 25947545
TI  - Predictors of long-term survival in patients with stage IV colorectal cancer with
      multi-organ metastases: a single-center retrospective analysis.
AB  - BACKGROUND: The prognosis for most patients with stage IV colorectal cancer (CRC)
      and multi-organ metastases is poor. However, little information is currently
      available on prognostic factors in these patients. The aim of this study was to
      identify predictors of a good prognosis in this patient group. METHODS: This was
      a single-center retrospective study in which we examined the relationship between
      patient characteristics and prognosis in 161 stage IV CRC patients with
      indications for first-line systemic chemotherapy. Cox proportional-hazards models
      were used to compute hazard ratios (HR) for death, adjusted for clinical and
      pathological characteristics. RESULTS: Of the 161 patients recruited to the
      study, 83 had single-organ and 78 had multi-organ metastases. Median survival
      time was significantly shorter in patients with multi-organ metastases than in
      those with single-organ metastases (19.2 vs. 42.0 months, respectively; log-rank,
      P < 0.001). There was no significant difference in survival between patients with
      metastases in two versus three or more organs (log-rank; P = 0.368). According to
      univariate analysis, primary tumor sites in the left side of the colon and in the
      rectum, a pretreatment carcinoembryonic antigen concentration of >50 ng/mL, a
      well-/moderately differentiated tumor, and R0 resection of metastatic lesions
      were associated with better overall survival. According to multivariate analysis,
      left-sided location of the primary tumor [HR 0.414, 95 % confidence interval (CI)
      0.216-0.815; P = 0.011] and R0 resection of metastatic lesions (HR 0.247, 95 % CI
      0.04 0-0.834; P = 0.021) were independently associated with good prognosis.
      CONCLUSIONS: Our results indicate that the site of the primary tumor in the left
      side of the colon and in the rectum and R0 resection of metastatic lesions are
      predictors of a good prognosis in patients with stage IV CRC and multi-organ
      metastases.

PMID- 25947546
TI  - I-131 remnant ablation after thyroidectomy induced hepatotoxicity in a case of
      thyroid cancer.
AB  - BACKGROUND: Radioactive iodine (I-131) is routinely used for the treatment of
      differentiated thyroid cancer following surgery. Drug-induced liver injury (DILI)
      is a leading cause of acute liver failure. Here we reported a rare case of
      diffuse hepatic uptake (DHU) of radioactive iodine (I-131) induced hepatotoxicity
      in patient with I-131 ablation therapy after thyroidectomy. CASE PRESENTATION: A
      57-year-old woman was admitted due to jaundice, itching and dark urine with
      abnormally elevated liver function. She has performed thyroidectomy followed by
      100 mci radioactive I-131 ablation therapy 21 days ago. The basic hepatic
      protection could not efficiently prevent disease progression. The patient was
      further treated with methylprednisolone, the bilirubin and alanin
      aminotransferase were finally lowered back to normal in the follow-up visit.
      CONCLUSION: To the best of our knowledge, this is the rare description of DILI
      complications in thyroidectomy patient due to I-131 ablation therapy. The patient
      responds to glucocorticoid therapy well, but not basic hepatic protection
      treatment. Even though this is only a single case, it reminds physicians make
      DILI in early consideration when patient present liver injury after I-131
      ablation therapy.

PMID- 25947547
TI  - Predictors of Survival in Ampullary, Bile Duct and Duodenal Cancers Following
      Pancreaticoduodenectomy: a 10-Year Multicentre Analysis.
AB  - INTRODUCTION: Predictors of survival following pancreaticoduodenectomy (PD) are
      well described for pancreatic cancers but are less detailed in ampullary (AC),
      bile duct (BDC) and duodenal cancers (DC). We therefore sought to evaluate the
      long-term results of PD for AC, BDC and DC, and to determine for each tumour the
      predictive factors of survival. METHODS: Medical charts of patients operated on
      between 2001 and 2011 were retrospectively reviewed. Univariate and multivariate
      analyses were performed to determine predictors of survival. RESULTS: One hundred
      thirty-five patients were identified. Mean follow-up was 47 +/- 33 months. Median
      survival was not reached for DC and was 66 and 24 months for AC and BDC,
      respectively. Two-year and five-year survival rates were 80 and 51% for DC and 69
      and 51% for AC, respectively. BDC had a significantly poorer prognosis, with two
      year and five-year survival rates of 51 and 34%, respectively. Predictors of
      survival were weight loss, N stage and International Union Against Cancer (UICC)
      stage for AC, T stage and resection margin status for BDC and N stage for DC.
      CONCLUSION: AC, BDC and DC display distinctive predictors of survival related to
      the biological aggressiveness. Preoperative malnutrition worsens the prognosis.
      The effect of adapted nutritional management on the survival improvement has to
      be studied.

PMID- 25947548
TI  - Impact of Nasojejunal Feeding on Outcome of Patients with Walled Off Pancreatic
      Necrosis (WOPN) Presenting with Pain: a Pilot Study.
AB  - BACKGROUND: Drainage is usually recommended in symptomatic walled off pancreatic
      necrosis (WOPN). WOPN presenting with pain may get symptomatic relief if the
      pancreas is given rest by initiating nasojejunal (NJ) feed. AIM: The aim of this
      was to prospectively study the efficacy of nasojejunal (NJ) feeding in patients
      of WOPN presenting with abdominal pain. METHODS: Twenty-one patients (15 M; 35 +/
      12 years) with WOPN (size 7-16 cm) presenting with pain underwent NJ tube
      placement under endoscopic guidance. Following this, pain relief and long-term
      outcome were studied. RESULTS: Etiology of pancreatitis was alcohol in 12, gall
      stones in 6, and idiopathic in 3 patients. NJ tube was successfully placed in all
      patients and 17/21 (81%) patients had symptomatic relief in 1-4 days (mean 2 +/-
      1 days) following NJ feeding. NJ tube was removed after 7-10 days (mean 7 +/- 1
      days), and 14 (61%) patients remained pain free and follow-up imaging (1-8
      months) revealed complete resolution or decrease in size of WOPN. Three patients
      had recurrence of pain and were successfully treated with endoscopic drainage.
      CONCLUSIONS: NJ feeding improves pain in the majority of patients with WOPN and
      thus obviates or delays drainage. Majority of nonresponders had disconnected
      pancreatic duct syndrome (DPDS).

PMID- 25947551
TI  - Regioselective Suzuki couplings of non-symmetric dibromobenzenes: alkenes as
      regiochemical control elements.
AB  - The regiochemical outcome of Suzuki couplings of non-symmetric dibromobenzenes is
      investigated. Selectivities are dependent on the proximity of the bromine atom to
      alkene substituents, not on steric or electronic effects. Extension to a one-pot
      three-component Suzuki reaction leads to efficient terphenyl syntheses. 

PMID- 25947549
TI  - Quantified Risk Assessment for Major Hepatectomy via the Indocyanine Green
      Clearance Rate and Liver Volumetry Combined with Standard Liver Volume.
AB  - BACKGROUND: Preoperative risk assessment for post-hepatectomy liver failure
      (PHLF) is essential for major hepatectomy. We intended to establish a standard
      liver volume (SLV) formula for Korean patients and validate the predictive power
      of the indocyanine green clearance rate constant (ICG-K) fraction of future
      remnant liver (FRL) (FRL-kICG) to total liver volume (TLV). METHODS: This study
      comprised 2 retrospective studies. Part I established SLV formula and acquired
      ICG pharmacokinetic data from 2155 living donors. In part II, FRL-kICG cutoff was
      determined using 723 patients who underwent right liver resection for
      hepatocellular carcinoma. RESULTS: In part I, the formula SLV (mL) = -456.3 +
      969.8 * BSA (m(2)) (r = 0.707, r (2) = 0.500, p = 0.000) was derived with mean
      volume error of 10.5%. There was no correlation between TLV and ICG retention
      rate at 15 min. With a cutoff of 0.04 with hepatic parenchymal resection rate
      (PHRR) limit of 70%, 99.0% of our living donors were permissible for left or
      right hepatectomy. In part II, 25 hepatocellular carcinoma patients (3.5%) showed
      an FRL-kICG or SLV-corrected FRL-kICG <0.05. Of these, 4 (16 %) died of PHLF,
      whereas only 2 (0.3%) died in the other patient group with both an FRL-kICG and
      SLV-corrected FRL-kICG >= 0.05 (P = 0.000). CONCLUSIONS: The FRL-kICG appears to
      reliably predict PHLF risk quantitatively. We suggest FRL-kICG cutoffs of 0.04
      and 0.05 with PHRR limits of 70% and 65% for normal and diseased livers,
      respectively. Further validation with large patient population in multicenter
      studies is necessary to improve FRL-kICG predictability.

PMID- 25947550
TI  - How individuals with the irritable bowel syndrome describe their own symptoms
      before formal diagnosis.
AB  - AIM: To investigate how individuals fulfilling the Rome II criteria for irritable
      bowel syndrome (IBS) spontaneously described their symptoms. METHOD: From a
      general population, 1,244 randomly sampled adults were asked to describe their
      gastrointestinal symptoms (if any) verbally, in their own words, at a semi
      structured interview. Their own descriptions were sorted into five symptom
      clusters. The participants independently completed a written questionnaire (the
      Rome II Modular Questionnaire (RMIIMQ)). RESULTS: A total of 601 participants
      reported at least one gastrointestinal symptom, and 128 had IBS according to the
      RMIIMQ. After exclusion of organic causes, previously diagnosed IBS, or
      additional gastrointestinal diagnosis, 81 participants with IBS according to
      RMIIMQ remained. Five participants (6%) described symptoms included in the full
      definition of IBS, but none fulfilled the Rome II criteria completely. Abdominal
      pain or other IBS-related symptoms were reported by 64 (79%), and 12 (15%) did
      not report any IBS-like symptom. CONCLUSION: Previously undiagnosed individuals,
      who fulfil criteria for Rome II-IBS, often express their complaints in words that
      do not fit into the current diagnostic criteria.

PMID- 25947552
TI  - Change in quality of life of patients undergoing silicone stent intubation for
      nasolacrimal duct stenosis combined with dry eye syndrome.
AB  - AIMS: To investigate the effect of silicone stent intubation (SI) on the quality
      of life of patients diagnosed with nasolacrimal duct stenosis and dry eye
      syndrome. METHODS: This study is a prospective, interventional case series.
      Consecutive 30 patients diagnosed with nasolacrimal duct stenosis and reflex
      tearing due to dry eye syndrome were included. Eligible subjects underwent SI and
      were asked to complete the Glasgow Benefit Inventory (GBI) questionnaire.
      Surgical outcomes and GBI scores were investigated 6 months postoperatively.
      RESULTS: The surgical success rate determined by the patients' subjective
      symptoms was 76.7% (23/30). Mean total GBI score was +17.19 (95% CI 8.34 to
      26.03). The general subscale score was +20.36 (95% CI 10.19 to 30.54), the social
      support scale score was +21.54 (95% CI 11.37 to 31.71) and the physical health
      score was -0.56 (95% CI -8.92 to 7.80). CONCLUSIONS: SI could be an effective
      treatment option for reflex tearing in patients diagnosed with dry eye syndrome
      and nasolacrimal duct stenosis.

PMID- 25947554
TI  - The association between toll-like receptor 4 polymorphisms and diabetic
      retinopathy in Chinese patients with type 2 diabetes.
AB  - PURPOSE: Diabetic retinopathy (DR) is one of the secondary microvascular
      complications of type 2 diabetes mellitus. Persistent inflammation and impaired
      neovascularisation may be important contributors to the development of DR. A
      recent study showed that toll-like receptor 4 (TLR4) polymorphisms were
      associated with DR. The present study was designed to determine whether single
      nucleotide polymorphisms (SNPs) in the TLR4 gene were associated with DR in a
      Chinese Han population. MATERIALS AND METHODS: Three SNPs (rs10759931, rs1927911
      and rs1927914) in the TLR4 gene were chosen as candidate SNPs. Genomic DNA from
      type 2 diabetes patients and healthy controls were genotyped for the above
      mentioned genetic variations through the use of PCR restriction fragment length
      polymorphism assay. Data were analysed by chi(2) analysis. RESULTS: The results
      showed that the three analysed polymorphisms in the TLR4 gene were in Hardy
      Weinberg equilibrium, both in the patients and in the controls. In the type 2
      diabetes group, a significantly higher frequency of the C allele of rs1927914 was
      observed in patients with type 2 diabetes than that in controls. The result
      showed that the frequencies of the TT genotype and the T allele of rs1927914 were
      significantly decreased in patients with type 2 diabetes. Significantly increased
      frequencies of the CC genotype and the C allele of rs1927911 were observed in
      patients with type 2 diabetes. In the DR group, the C allele of rs1927914 was
      significantly increased in the DR group compared with that of the control. The
      frequencies of the CC genotype and the C allele of rs1927911 tended to be higher
      in patients with DR than in the healthy controls. However, no difference was
      found when the Bonferroni correction was applied. No difference was detected
      between patients and controls with regard to all haplotypes. CONCLUSIONS: This
      study suggested that rs1927914 and rs1927911 were associated with type 2 diabetes
      mellitus and that rs1927914 was associated with susceptibility to DR in a Han
      Chinese population.

PMID- 25947555
TI  - IgG4-related disease in idiopathic sclerosing orbital inflammation.
AB  - AIMS: To investigate the frequency of IgG4-related disease (IgG4-RD) among
      patients previously diagnosed with idiopathic sclerosing orbital inflammation
      (ISOI), and to compare the clinical features and treatment outcomes of patients
      with ISOI associated with IgG4-RD and those without IgG4. METHODS: Retrospective
      clinicopathological series of 24 patients with ISOI diagnosed between June 2001
      and June 2010. Biopsy specimens were immunostained for IgG-expressing and IgG4
      expressing cells. Clinical data of patients with IgG4-RD and ISOI unrelated to
      IgG4 were obtained from patient records. RESULTS: Of 24 patients, 11 patients
      (45.8%) were identified with IgG4-RD. 10 patients (10/11, 90.9%) presented with
      bilateral lacrimal gland enlargement, and seven of those also had submadibular
      gland enlargement. One patient (1/11, 9.1%) presented with a superior orbital
      mass. All patients were successfully treated with steroids and/or radiotherapy or
      had an indolent clinical course. 13 patients (54.2%) were identified with ISOI
      unrelated to IgG4. Eight patients (8/13, 61.5%) showed unilateral orbital
      involvement, and nine patients (9/13, 69.2%) had orbital lesions not involving
      the lacrimal glands. Treatment modalities for ISOI unrelated to IgG4 were varied
      and less effective: eight patients (61.5%) relapsed following initial treatment
      with steroids or radiation, and additional therapies were required to enter
      remission. CONCLUSIONS: IgG4-RD may be identified frequently in patients with
      ISOI, and distinguishing features may be bilateral lacrimal gland enlargement
      with associated submandibular gland enlargement. Patients with IgG4-RD may have
      better treatment outcomes with less aggressive treatment modalities than those
      with ISOI unrelated to IgG4. An additional workup for IgG4-RD should be
      considered in all histopathological biopsy specimens suspicious of ISOI.

PMID- 25947556
TI  - Risk factors for the development of ocular graft-versus-host disease (GVHD) dry
      eye syndrome in patients with chronic GVHD.
AB  - BACKGROUND: To investigate the factors associated with the development of ocular
      graft-versus-host disease (oGVHD) dry eye syndrome (DES) in patients with chronic
      GVHD (cGVHD) after receiving allogenic haematopoietic stem cell transplantation
      (AHSCT) METHODS: A retrospective chart review of patients receiving AHSCT between
      1998 and 2013 at the Bone Marrow Transplant Unit of the British Columbia Cancer
      Agency was carried out. Demographic and clinical data from both donors and
      recipients were obtained. The diagnostic criteria for the development of oGVHD
      DES from the National Institutes of Health were used to identify patients with
      the disease. Descriptive and inferential statistics were carried out. RESULTS: A
      total of 146 patients with a median follow-up time of 24.0 months (range 11.3
      249.7 months) were included in this study. Sixty-six (45.2%) patients were women.
      Seventy-seven (52.7%) patients had oGVHD DES. The median age of patients was 57
      years (range 25-71 years). Compared with other ethnicities, Caucasian patients
      were less likely to develop oGVHD DES, with an OR of 0.29 (p=0.01). Patients who
      received a transplant from Epstein-Barr-positive donors had a higher prevalence
      of oGVHD DES (OR=4.39, p=0.01). This was also found in patients with the
      following systemic involvement of cGVHD: grade 1-3 cGVHD skin involvement
      (OR=1.57, p=0.01), oral involvement (OR=2.51, p=0.01) and liver involvement
      (p=0.04). Patients with grade 2-3 overall cGVHD were also more susceptible to
      oGVHD DES (OR=2.72, p<0.001). CONCLUSIONS: This study identified risk factors
      associated with a higher prevalence of oGVHD DES in post-AHSCT patients with
      cGVHD.

PMID- 25947553
TI  - Risks and outcomes associated with primary intraocular lens implantation in
      children under 2 years of age: the IoLunder2 cohort study.
AB  - BACKGROUND/AIMS: To investigate outcomes following cataract surgery with and
      without primary intraocular lens (IoL) implantation in children under 2 years of
      age with congenital or infantile cataract. METHOD: Prospective population based
      cohort study undertaken through the British Isles Congenital Cataract Interest
      Group, with systematic data collection on children undergoing surgery in UK and
      Ireland between January 2009 and December 2010. ORs for the association between
      IoL implantation and visual acuity, postoperative glaucoma and reoperation at 1
      year after surgery were estimated using multivariable regression analysis to
      control for potential confounders. RESULTS: Of 221 children, 56/131 with
      bilateral and 48/90 with unilateral cataract underwent primary IoL implantation.
      IoL implantation was independently associated with better visual outcome in
      bilateral (OR 4.6, 95% CI 1.6 to 13.1, p=0.004) but not unilateral disease. IoL
      use increased the odds of reoperation requiring repeat general anaesthetic
      (bilateral OR 5.5, p<0.01; unilateral OR 16.7, p<0.01). IoL implantation did not
      reduce the odds of postoperative glaucoma. CONCLUSIONS: The use of IoLs in
      cataract surgery in young children should be critically reassessed, particularly
      used in settings/communities where close, long-term follow-up is challenging. The
      absence of visual benefit and the lack of a previously postulated protective
      effect against postoperative glaucoma serve to question the value of IoLs in
      unilateral disease. The potential association between IoL use and better early
      visual outcomes in bilateral disease needs to be balanced against the risk of
      reoperation and exposure to additional general anaesthetics during a key period
      of neurodevelopment.

PMID- 25947557
TI  - Anterior chamber gas bubble emergence pattern during femtosecond LASIK-flap
      creation.
AB  - AIM: To characterise the emergence pattern of cavitation bubbles into the
      anterior chamber (AC) following femtosecond laser-assisted in situ keratomileusis
      (LASIK)-flap creation METHODS: Retrospective review of patients undergoing
      femtosecond LASIK surgery at Boston Laser, a private refractive surgery practice
      in Boston, Massachusetts, between December 2008 and February 2014. Patient charts
      were reviewed to identify all cases with gas bubble migration into the AC.
      Surgical videos were examined and the location of bubble entry was recorded
      separately for right and left eyes. RESULTS: Five thousand one hundred and fifty
      eight patients underwent femtosecond LASIK surgery. Air bubble migration into the
      AC, presumably via the Schlemm's canal and trabecular meshwork, occurred in 1% of
      cases. Patients with AC bubbles had an average age of 33+/-8 years with a
      measured LASIK flap thickness of 96+/-21 MUm. The occurrence of gas bubbles
      impaired iris registration in 64% of cases. Gas bubbles appeared preferentially
      in the nasal or inferior quadrants for right (92% of cases) and left (100% of
      cases) eyes. This bubble emergence pattern is significantly different from that
      expected with a random distribution (p<0.0001) and did not seem associated with
      decentration of the femtosecond laser docking system. CONCLUSIONS: The migration
      of gas bubbles into the AC is a rare occurrence during femtosecond laser flap
      creation. The preferential emergence of gas bubbles into the nasal and inferior
      quadrants of the AC may indicate a distinctive anatomy of the nasal Schlemm's
      canal.

PMID- 25947558
TI  - Cost-effectiveness analysis of clinic-based chloral hydrate sedation versus
      general anaesthesia for paediatric ophthalmological procedures.
AB  - BACKGROUND/AIMS: The inability of some children to tolerate detailed eye
      examinations often necessitates general anaesthesia (GA). The objective was to
      assess the incremental cost effectiveness of paediatric eye examinations carried
      out in an outpatient sedation unit compared with GA. METHODS: An episode of care
      cost-effectiveness analysis was conducted from a societal perspective. Model
      inputs were based on a retrospective cross-over cohort of Canadian children aged
      <7 years who had both an examination under sedation (EUS) and examination under
      anaesthesia (EUA) within an 8-month period. Costs ($CAN), adverse events and
      number of successful procedures were modelled in a decision analysis with one-way
      and probabilistic sensitivity analysis. RESULTS: The mean cost per patient was
      $406 (95% CI $401 to $411) for EUS and $1135 (95% CI $1125 to $1145) for EUA. The
      mean number of successful procedures per patient was 1.39 (95% CI 1.34 to 1.42)
      for EUS and 2.06 (95% CI 2.02 to 2.11) for EUA. EUA was $729 more costly on
      average than EUS (95% CI $719 to $738) but resulted in an additional 0.68
      successful procedures per child. The result was robust to varying the cost
      assumptions. CONCLUSIONS: Cross-over designs offer a powerful way to assess costs
      and effectiveness of two interventions because patients serve as their own
      control. This study demonstrated significant savings when ophthalmological exams
      were carried out in a hospital outpatient clinic, although with slightly fewer
      procedures completed.

PMID- 25947560
TI  - Don't mention the P word.

PMID- 25947559
TI  - AcPIP2, a plasma membrane intrinsic protein from halophyte Atriplex canescens,
      enhances plant growth rate and abiotic stress tolerance when overexpressed in
      Arabidopsis thaliana.
AB  - KEY MESSAGE: An aquaporin protein AcPIP2 from Atriplex canescens was involved in
      plant growth rate, abiotic stress tolerance in Arabidopsis. Under limited water
      condition, AcPIP2 leaded to the sensitivity to drought stress. An aquaporin
      protein (AcPIP2) was obtained from the saltbush Atriplex canescens, which was in
      PIP2 subgroup belonging to the PIP subfamily, MIP superfamily. The subcellular
      localization of AcPIP2 showed the fusion protein AcPIP2-eGFP located at the
      plasma membrane in Nicotiana benthamiana. Overexpression of AcPIP2 in Arabidopsis
      fully proved that AcPIP2 was involved in plant growth rate, transpiration rate
      and abiotic stress tolerance (NaCl, drought and NaHCO3) in Arabidopsis, which is
      mostly in correspondence to gene expression pattern characterized by qRT-PCR
      performed in A. canescens. And under limited water condition, AcPIP2
      overexpression leaded to the sensitivity to drought stress. In the view of the
      resistant effect in transgenic Arabidopsis overexpressing AcPIP2, the AcPIP2 may
      throw some light into understanding how the A. canescens plants cope with abiotic
      stress, and could be used in the genetic engineering to improve plant growth or
      selective tolerance to the abiotic stress.

PMID- 25947561
TI  - The first case of feline sinonasal aspergillosis due to Aspergillus fischeri in
      Japan.
AB  - Feline upper respiratory tract infection due to Aspergillus spp. is considered an
      emerging disease, with the number of reported cases continuing to rise. In this
      study, we report the first case of feline sinonasal aspergillosis caused by
      Aspergillus fischeri in Japan. The patient presented after 2 months of
      progressive facial deformity around the nose and nasal discharge. The isolate
      from this case was susceptible to itraconazole (ITZ), voriconazole and
      micafungin, but was resistant to amphotericine B. However, the infected cat died
      approximately 1 month after referral, despite treatment for 12 days ITZ
      administered orally at 10 mg/kg.

PMID- 25947562
TI  - Mycotic aneurysm caused by Graphium species in a dog.
AB  - A 10-year-old castrated male mixed-breed dog exhibited vomiting, lethargy and
      anorexia. An abdominal ultrasound examination revealed a focal dilation of the
      abdominal aorta. The dog died 2 days after examination, and necropsy revealed a
      ruptured aneurysm at the abdominal aorta between the kidneys. Histological
      examination revealed severe granulomatous and necrotizing pan-arteritis with
      fungal organisms. Graphium species was identified through DNA sequence analysis
      of the PCR product from formalin-fixed paraffin-embedded samples. To our
      knowledge, this is the first report of aortic aneurysm caused by Graphium species
      in a dog. Sequence was submitted to the DNA Data Bank of Japan with the accession
      number LC007972.

PMID- 25947563
TI  - Anti-emetic drug maropitant induces intestinal motility disorder but not anti
      inflammatory action in mice.
AB  - Maropitant is a neurokinin 1 receptor (NK1R) antagonist that is clinically used
      as a new anti-emetic drug for dogs. Substance P (SP) and its receptor NK1R are
      considered to modulate gastrointestinal peristalsis. In addition, SP works as an
      inflammatory mediator in gastrointestinal diseases. Aim of this study is to
      clarify the effects of maropitant on intestinal motility and inflammation in
      mice. Ex vivo examination of luminal pressure-induced intestinal motility of
      whole intestine revealed that maropitant (0.1-10 uM) increased frequency of
      contraction, decreased amplitude of contraction and totally inhibited motility
      index in a concentration-dependent manner. We measured intestinal transit in vivo
      by measuring transportation of orally administered luminal content labeled with
      phenol red. Our results demonstrated that maropitant (10 mg/kg, SC) delayed
      intestinal transit. Geometric center value was significantly decreased in
      maropitant-treated mice. Anti-inflammatory effects of maropitant against
      leukocytes infiltration into the intestinal smooth muscle layer in post-operative
      ileus (POI) model mice were measured by immunohistochemistry. In POI model mice,
      a great number of CD68-positive macrophages or MPO-stained neutrophils
      infiltrated into the inflamed muscle region of the intestine. However, in the
      maropitant treated mice, the infiltration of leukocytes was not inhibited. The
      results indicated that maropitant has ability to induce disorder of intestinal
      motility in mice, but has no anti-inflammatory action in the mouse of a POI
      model. In conclusion, in mice, maropitant induces disorder of intestinal motility
      in vivo. 

PMID- 25947564
TI  - Contesting heteronormativity: the fight for lesbian, gay, bisexual and
      transgender recognition in India and Vietnam.
AB  - Recent public debates about sexuality in India and Vietnam have brought the
      rights of lesbian, gay, bisexual and transgender people sharply into focus.
      Drawing on legal documents, secondary sources and ethnographic fieldwork
      conducted in the urban centres of Delhi and Hanoi, this article shows how the
      efforts of civil society organisations dedicated to the fight for lesbian, gay,
      bisexual and transgender rights have had different consequences in these two
      Asian contexts. The paper considers how these organisations navigated government
      regulations about their formation and activities, as well as the funding
      priorities of national and international agencies. The HIV epidemic has had
      devastating consequences for gay men and other men who have sex with men, and has
      been highly stigmatising. As a sad irony, the epidemic has provided at the same
      time a strategic entry point for organisations to struggle for lesbian, gay,
      bisexual and transgender recognition. This paper examines how the fight for
      lesbian, gay, bisexual and transgender recognition has been doubly framed through
      health-based and rights-based approaches and how the struggle for recognition has
      positioned lesbian, gay, bisexual and transgender people in India and Vietnam
      differently. 

PMID- 25947565
TI  - A phase 1 study with dose expansion of the CDK inhibitor dinaciclib (SCH 727965)
      in combination with epirubicin in patients with metastatic triple negative breast
      cancer.
AB  - PURPOSE: Low molecular weight cyclin E (LMW-E) isoforms, overexpressed in a
      majority (~70 %) of triple-negative breast cancers (TNBC), were found in
      preclinical models to mediate tumorigenesis through binding and activation of
      CDK2. CDK1/CDK2 inhibitors, such as dinaciclib, combined with anthracyclines,
      were synergistic in decreasing viability of TNBC cell lines. Based on this data,
      a phase 1 study was conducted to determine the maximum tolerated dose of
      dinaciclib in combination with epirubicin in patients with metastatic TNBC.
      METHODS: Cohorts of at least 2 patients were treated with escalating doses of
      dinaciclib given on day 1 followed by standard dose of epirubicin given on day 2
      of a 21 day cycle. No intra-patient dose escalation was allowed. An adaptive
      accrual design based upon toxicity during cycle 1 determined entry into therapy
      cohorts. The target acceptable dose limiting toxicity (DLT) to advance to the
      next treatment level was 30 %. RESULTS: Between 9/18/2012 and 7/18/2013, 9
      patients were enrolled and treated at MD Anderson Cancer Center. DLTs included
      febrile neutropenia (grade 3, n = 2), syncope (grade 3, n = 2) and vomiting
      (grade 3, n = 1). Dose escalation did not proceed past the second cohort due to
      toxicity. After further accrual, the first dose level was also found to be too
      toxic. No treatment responses were noted, median time to progression was 5.5
      weeks (range 3-12 weeks). Thus, accrual was stopped rather than explore the -1
      dose level. CONCLUSION: The combination of dinaciclib and epirubicin is
      associated with substantial toxicities and does not appear to be an effective
      treatment option for TNBC.

PMID- 25947566
TI  - First-in-human, phase I study of elisidepsin (PM02734) administered as a 30-min
      or as a 3-hour intravenous infusion every three weeks in patients with advanced
      solid tumors.
AB  - This first-in-human, phase I clinical trial was designed to determine the dose
      limiting toxicities (DLTs) and the dose for phase II trials (P2D) of elisidepsin
      (PM02734) administered as a 30-min or as a 3-h intravenous infusion every 3 weeks
      (q3wk). Between March 2006 and April 2011, 53 patients with advanced malignant
      solid tumors were enrolled and treated with elisidepsin on the two different q3wk
      infusion schedules: 22 (30-min) and 31 (3-h), respectively. Doses evaluated
      ranged from 0.1 to 1.6 mg/m(2) (30-min q3wk) and from 2.0 to 11.0 mg flat dose
      (FD) (3-h q3wk). In the 30-min q3wk schedule, transient grade 3/4 increases in
      hepatic transaminases were the DLT, which appeared at the highest doses tested
      (from 1.1 to 1.6 mg/m(2)). No DLTs were observed on the 3-h schedule at doses up
      to 11.0 mg q3wk. Common adverse events were grade 1/2 pruritus, nausea, fatigue
      and hypersensitivity. Of note, myelotoxicity was not observed. Plasma maximum
      concentration and total drug exposure increased linearly with dose. Prolonged
      (>=3 months) disease stabilization was observed in pretreated patients with
      pleural mesothelioma (n = 1) in the 30-min q3wk arm, and with colorectal
      adenocarcinoma (n = 3), esophagus adenocarcinoma, endometrium adenocarcinoma,
      pleural mesothelioma, and head and neck carcinoma (n = 1 each) in the 3-h q3wk
      arm. In conclusion, elisidepsin doses of 1.1 mg/m(2) (equivalent to a FD of 2.0
      mg) and 11.0 mg FD are the dose levels achieved for further phase II trials
      testing the 30-min q3wk and 3-h q3wk schedules, respectively.

PMID- 25947567
TI  - The effect of paclitaxel and nab-paclitaxel in combination with anti-angiogenic
      therapy in breast cancer cell lines.
AB  - Taxanes represent a treatment of choice for metastatic breast cancer. Their
      combination with bevacizumab improved response rate and progression-free
      survival. We studied in vitro the effect on cell survival of the combination of
      either paclitaxel or nab-paclitaxel with bevacizumab and we investigated the
      biological factors involved in the response to treatments. We used two breast
      cancer cell lines, MCF7 (ER+/HER2-) and MDA-MB-231 (ER-/HER2-), co-cultured with
      or without HUVEC cells. We analysed cell survival by MTT test, VEGF secretion by
      ELISA and VEGFR, SPARC, MDR1 expression by western blot. Doses of both taxanes
      causing a 50 % growth inhibition were higher in MCF7 than MDA-MB-231, suggesting
      that taxanes are more effective in ER- cell lines. When both cell lines were
      grown as single culture, the combination bevacizumab+paclitaxel showed a similar
      anti-proliferative effect compared to paclitaxel alone. The association
      bevacizumab+nab-paclitaxel was more effective than nab-paclitaxel alone. An
      increased anti-proliferative effect of bevacizumab+paclitaxel was observed when
      MDA-MB-231 cells were cultured with HUVEC. We detected an induction of VEGF
      secretion when MDA-MB-231 cells were treated with either taxanes. Paclitaxel
      caused a reduction of VEGF in MCF7. SPARC resulted up-regulated in both cell
      lines treated with bevacizumab+nab-paclitaxel. Nab-paclitaxel seems to play an
      important role in inhibiting tumor proliferation through albumin-SPARC bound in
      association with bevacizumab compared to taxanes alone in both breast cancer
      cells. The addition of bevacizumab to paclitaxel increased its activity only in
      ER- cells. This difference might be due to their ER status. 

PMID- 25947568
TI  - Patient-Reported Barriers and Limitations to Attending Diabetes Group Visits.
AB  - PURPOSE: Through this exploratory study, we sought to understand why group visit
      participation is low among adult patients with type 2 diabetes. METHODS: Eligible
      study participants included adult patients with type 2 diabetes. After a pilot
      survey was sent to a random sample of 48 patients, the remaining 187 eligible
      patients were invited to complete a revised version of the survey. RESULTS: Most
      frequently cited reasons for not attending group visits included diabetes under
      control, work and/or other responsibilities, and time barriers. There was
      variability in the desired time for the visits, though the majority of patients
      preferred evening visits. While some patients reported copays as a challenge, the
      likelihood of attending did not decrease for this subgroup. Most patients
      surveyed (54%) indicated interest in diabetes group visits. CONCLUSION:
      Implementing strategies to address the patient-identified system barriers (eg,
      time, transportation, and copays) may increase participation in diabetes group
      visits.

PMID- 25947569
TI  - Characterization and comparative analysis of promoters from three plant
      pararetroviruses associated with Dahlia (Dahlia variabilis).
AB  - Two distinct caulimoviruses, Dahlia mosaic virus (DMV) and Dahlia common mosaic
      virus (DCMV), and an endogenous plant pararetroviral sequence (DvEPRS, formerly
      known as DMV-D10) were reported from dahlia (Dahlia spp). Promoter elements from
      these dahlia-associated pararetroviruses were identified and characterized. The
      TATA box, the CAAT box, the transcription start site, the polyadenylation signal,
      and regulation factors, characteristic of caulimovirus promoters, were present in
      each of these promoter regions. Each of the promoter regions was separately
      cloned into a binary vector containing beta-glucuronidase (GUS) reporter gene and
      delivered into Agrobacterium tumefaciens by electroporation followed by
      agroinfiltration into Nicotiana benthamiana. The activity of the 35S promoter
      homologs was determined by transient expression of the GUS gene both in
      qualitative and quantitative assays. The length of the promoter regions in DMV,
      DCMV, and DvEPRS corresponded to 438, 439, and 259 bp, respectively. Quantitative
      GUS assays showed that the promoters from DMV and DCMV resulted in higher levels
      of gene expression compared to that of DvEPRS in N. benthamiana leaf tissue.
      Significant differences were observed among the three promoters (p < 0.001).
      Qualitative GUS assays were consistent with quantitative GUS results. This study
      provides important information on new promoters for prospect applications as
      novel promoters for their potential use in foreign gene expression in plants.

PMID- 25947570
TI  - Autophagy in endocrine tumors.
AB  - Autophagy is an important intracellular process involving the degradation of
      cytoplasmic components. It is involved in both physiological and pathological
      conditions, including cancer. The role of autophagy in cancer is described as a
      'double-edged sword,' a term that reflects its known participation in tumor
      suppression, tumor survival and tumor cell proliferation. Available research
      regarding autophagy in endocrine cancer supports this concept. Autophagy shows
      promise as a novel therapeutic target in different types of endocrine cancer,
      inhibiting or increasing treatment efficacy in a context- and cell-type-dependent
      manner. At present, however, there is very little research concerning autophagy
      in endocrine tumors. No research was reported connecting autophagy to some of the
      tumors of the endocrine glands such as the pancreas and ovary. This review aims
      to elucidate the roles of autophagy in different types of endocrine cancer and
      highlight the need for increased research in the field. 

PMID- 25947571
TI  - One-size MAP does not fit all.

PMID- 25947572
TI  - Alterations of left ventricular deformation and cardiac sympathetic derangement
      in patients with systolic heart failure: a 3D speckle tracking echocardiography
      and cardiac 123I-MIBG study.
AB  - PURPOSE: Myocardial contractile function is under the control of cardiac
      sympathetic activity. Three-dimensional speckle tracking echocardiography (3D
      STE) and cardiac imaging with (123)I-metaiodobenzylguanidine ((123)I-MIBG) are
      two sophisticated techniques for the assessment of left ventricular (LV)
      deformation and sympathetic innervation, respectively, which offer important
      prognostic information in patients with heart failure (HF). The purpose of this
      investigation was to explore, in patients with systolic HF, the relationship
      between LV deformation assessed by 3D-STE and cardiac sympathetic derangement
      evaluated by (123)I-MIBG imaging. METHODS: We prospectively studied 75 patients
      with systolic HF. All patients underwent a 3D-STE study (longitudinal,
      circumferential, area and radial) and (123)I-MIBG planar and SPECT cardiac
      imaging. RESULTS: 3D-STE longitudinal, circumferential and area strain values
      were correlated with (123)I-MIBG late heart to mediastinum (H/M) ratio and late
      SPECT total defect score. After stratification of the patients according to
      ischaemic or nonischaemic HF aetiology, we observed a good correlation of all 3D
      STE measurements with late H/M ratio and SPECT data in the ischaemic group, but
      in patients with HF of nonischaemic aetiology, no correlation was found between
      LV deformation and cardiac sympathetic activity. At the regional level, the
      strongest correlation between LV deformation and adrenergic innervation was found
      for the left anterior descending coronary artery distribution territory for all
      four 3D-STE values. In multivariate linear regression analyses, including age,
      gender, LV ejection fraction, NYHA class, body mass index, heart rate and HF
      aetiology, only 3D-STE area and radial strain values significantly predicted
      cardiac sympathetic derangement on (123)I-MIBG late SPECT. CONCLUSION: This study
      indicated that 3D-STE measurements are correlated with (123)I-MIBG planar and
      SPECT data. Furthermore, 3D-STE area and radial strain values, but not LVEF,
      predict cardiac sympathetic derangement in human postischaemic HF.

PMID- 25947573
TI  - 99mTc-3PRGD2 SPECT to monitor early response to neoadjuvant chemotherapy in stage
      II and III breast cancer.
AB  - PURPOSE: Monitoring of response to neoadjuvant chemotherapy (NCT) is important
      for optimal management of patients with breast cancer. (99m)Tc-3PRGD2 SPECT is a
      newly developed imaging modality for evaluating tumor vascular status. In this
      study, we investigated the application of (99m)Tc-3PRGD2 SPECT in evaluating
      therapy response to NCT in patients with stage II or III breast cancer. METHODS:
      Thirty-three patients were scheduled to undergo (99m)Tc-3PRGD2 SPECT at baseline,
      after the first and second cycle of NCT. Four patients had extremely low (99m)Tc
      3PRGD2 uptake at baseline, and were not included in the subsequent studies.
      Changes in tumor to nontumor (T/N) ratio were compared with pathological tumor
      responses classified using the residual cancer burden system. Receiver operator
      characteristic analysis was used to compare the power to identify responders
      between the end of the first and the end of the second cycle of NCT. The impact
      of breast cancer subtype on (99m)Tc-3PRGD2 uptake was evaluated. The correlation
      between (99m)Tc-3PRGD2 uptake and pathological tumor response was also evaluated
      in each breast cancer subtype. RESULTS: Surgery was performed after four cycles
      of NCT and pathological analysis revealed 18 responders and 15 nonresponders. In
      patients with clearly visible (99m)Tc-3PRGD2 uptake at baseline, the sensitivity,
      specificity, and negative predictive value of (99m)Tc-3PRGD2 SPECT were 86.7 %,
      85.7 % and 86.7 % after the first cycle of NCT, and 92.9 %, 93.3 % and 93.3 %
      after the second cycle, respectively. Among these patients, the HER-2-positive
      group demonstrated both higher T/N ratios and a greater change in T/N ratio than
      patients with other breast cancer subtypes (P < 0.05). A strong correlation was
      found between changes in T/N ratio and pathological tumor response in the HER-2
      positive group (P < 0.03). CONCLUSION: (99m)Tc-3PRGD2 SPECT seems to be useful
      for determining the pathological tumor response in patients with stage II or III
      breast cancer undergoing NCT, especially those with the HER-2-positive subtype.

PMID- 25947574
TI  - Pulmonary tuberculosis mimicking pulmonary metastases on 131I post-therapeutic
      scan.

PMID- 25947575
TI  - Association between 18F-FDG uptake and molecular subtype of breast cancer.
AB  - PURPOSE: To determine whether (18)F-FDG uptake in breast cancer correlates with
      immunohistochemically defined subtype and is able to predict molecular subtypes.
      METHODS: This retrospective study involved 306 patients with 308 mass-type
      invasive breast cancers (mean size 2.65 cm, range 1.0-15.0 cm) who underwent
      (18)F-FDG PET/CT before therapy. The correlations between primary tumour (18)F
      FDG uptake on PET/CT, expressed as SUVmax, and clinicopathological findings and
      molecular subtype, i.e. luminal A, luminal B (HER2-negative), luminal B (HER2
      positive), HER2-positive and triple-negative, were analysed. The predictors of
      these subtypes were investigated. RESULTS: The mean SUVmax of the 308 tumours was
      5.33 +/- 3.63 (range 1.15-19.01). Among the subtypes of the 308 tumours, 87 (28.2
      %) were luminal A, 111 (36.0 %) were luminal B (HER2-negative), 31 (10.1 %) were
      luminal B (HER2-positive), 26 (8.4 %) were HER2-positive and 53 (17.2 %) were
      triple-negative, and the corresponding mean SUVmax were 3.41 +/- 2.07 (range 1.18
      14.30), 5.17 +/- 3.52 (range 1.35-19.01), 6.57 +/- 3.84 (range 1.42-15.58), 7.55
      +/- 3.63 (range 2.30-13.60) and 6.97 +/- 4.17 (range 1.15-16.06), respectively. A
      cut-off value of 3.60 yielded 70.1 % sensitivity and 66.1 % specificity with an
      area under the receiver operating characteristics curve (AUC) of 0.734 for
      predicting that a tumour was of the luminal A subtype. A cut-off value of 6.75
      yielded 65.4 % sensitivity and 75.2 % specificity with an AUC of 0.704 for
      predicting a HER2-positive subtype. CONCLUSION: SUVmax, a metabolic
      semiquantitative parameter, shows a significant correlation with the molecular
      subtype of breast cancer, and is useful for predicting the luminal A or HER2
      positive subtype.

PMID- 25947576
TI  - Radioembolization with (90)Y-loaded microspheres: high clinical impact of
      treatment simulation with MAA-based dosimetry.

PMID- 25947577
TI  - Gene transcript analysis blood values correlate with 68Ga-DOTA-somatostatin
      analog (SSA) PET/CT imaging in neuroendocrine tumors and can define disease
      status.
AB  - PURPOSE: Precise determination of neuroendocrine tumor (NET) disease status and
      response to therapy remains a rate-limiting concern for disease management. This
      reflects limitations in biomarker specificity and resolution capacity of imaging.
      In order to evaluate biomarker precision and identify if combinatorial blood
      molecular markers and imaging could provide added diagnostic value, we assessed
      the concordance between (68)Ga-somatostatin analog (SSA) positron emission
      tomography (PET), circulating NET gene transcripts (NETest), chromogranin A
      (CgA), and Ki-67 in NETs. METHODS: We utilized two independent patient groups
      with positive (68)Ga-SSA PET: data set 1 ((68)Ga-SSA PETs undertaken for peptide
      receptor radionuclide therapy (PRRT), as primary or salvage treatment, n = 27)
      and data set 2 ((68)Ga-SSA PETs performed in patients referred for initial
      disease staging or restaging after various therapies, n = 22). We examined the
      maximum standardized uptake value (SUVmax), circulating gene transcripts, CgA
      levels, and baseline Ki-67. Regression analyses, generalized linear modeling, and
      receiver-operating characteristic (ROC) analyses were undertaken to determine the
      strength of the relationships. RESULTS: SUVmax measured in two centers were
      mathematically evaluated (regression modeling) and determined to be comparable.
      Of 49 patients, 47 (96 %) exhibited a positive NETest. Twenty-six (54 %) had
      elevated CgA (chi(2) = 20.1, p < 2.5*10(-6)). The majority (78 %) had Ki-67 < 20
      %. Gene transcript scores were predictive of imaging with >95 % concordance and
      significantly correlated with SUVmax (R (2) = 0.31, root-mean-square error =
      9.4). The genes MORF4L2 and somatostatin receptors SSTR1, 3, and 5 exhibited the
      highest correlation with SUVmax. Progressive disease was identified by elevated
      levels of a quotient of MORF4L2 expression and SUVmax [ROC-derived AUC (R (2) =
      0.7, p < 0.05)]. No statistical relationship was identified between CgA and Ki-67
      and no relationship with imaging parameters was evident. CONCLUSION: (68)Ga-SSA
      PET imaging parameters (SUVmax) correlated with a circulating NET transcript
      signature. Disease status could be predicted by an elevated quotient of gene
      expression (MORF4L2) and SUVmax. These observations provide the basis for further
      exploration of strategies that combine imaging parameters and disease-specific
      molecular data for the improvement of NET management.

PMID- 25947579
TI  - Happiness increases verbal and spatial working memory capacity where sadness does
      not: Emotion, working memory and executive control.
AB  - The effects of emotion on working memory and executive control are often studied
      in isolation. Positive mood enhances verbal and impairs spatial working memory,
      whereas negative mood enhances spatial and impairs verbal working memory.
      Moreover, positive mood enhances executive control, whereas negative mood has
      little influence. We examined how emotion influences verbal and spatial working
      memory capacity, which requires executive control to coordinate between holding
      information in working memory and completing a secondary task. We predicted that
      positive mood would improve both verbal and spatial working memory capacity
      because of its influence on executive control. Positive, negative and neutral
      moods were induced followed by completing a verbal (Experiment 1) or spatial
      (Experiment 2) working memory operation span task to assess working memory
      capacity. Positive mood enhanced working memory capacity irrespective of the
      working memory domain, whereas negative mood had no influence on performance.
      Thus, positive mood was more successful holding information in working memory
      while processing task-irrelevant information, suggesting that the influence mood
      has on executive control supersedes the independent effects mood has on domain
      specific working memory. 

PMID- 25947578
TI  - Testing the feasibility of a mobile technology intervention promoting healthy
      gestational weight gain in pregnant women (txt4two) - study protocol for a
      randomised controlled trial.
AB  - BACKGROUND: Overweight, obesity and excess gestational weight gain (GWG) are
      associated with negative health outcomes for mother and child in pregnancy and
      across the life course. Interventions promoting GWG within guidelines report
      mixed results. Most are time and cost intensive, which limits scalability. Mobile
      technologies (mHealth) offer low cost, ready access and individually-tailored
      support. We aim to test the feasibility of an mHealth intervention promoting
      healthy nutrition, physical activity and GWG in women who begin pregnancy
      overweight or obese. METHODS/DESIGN: txt4two is a parallel randomised control
      trial pilot recruiting women with a singleton, live gestation between 10(+0) and
      17(+6) weeks at the first hospital antenatal clinic visit. Inclusion criteria are
      pre-pregnancy BMI > 25 kg/m(2) and mobile phone ownership. One hundred consenting
      women will be randomised to intervention or control groups at a 1:1 ratio. All
      participants will receive standard antenatal care. In addition, the txt4two
      intervention will be delivered from baseline to 36 weeks gestation and consists
      of a tailored suite of theoretically-grounded, evidence-based intervention
      strategies focusing on healthy nutrition, physical activity and GWG. This
      includes: mobile phone interactive text messages promoting positive health
      behaviours, goal setting and self-monitoring; video messages; an information
      website; and a private moderated Facebook(r) chat forum. The primary outcome is
      the feasibility of the intervention. Secondary outcomes include GWG and
      participants' knowledge and behaviour regarding diet and physical activity during
      pregnancy. DISCUSSION: Findings will inform the development of larger-scale
      mHealth programmes to improve the delivery of healthy pregnancy nutrition,
      physical activity and GWG, that could be widely translated and disseminated.
      TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry:
      ACTRNU111111544397 . Date of registration: 19 March 2014.

PMID- 25947580
TI  - Risk of Amyotrophic Lateral Sclerosis in Patients With Diabetes: A Nationwide
      Population-Based Cohort Study.
AB  - BACKGROUND: Glucose intolerance in patients with amyotrophic lateral sclerosis
      (ALS) has been inconsistently reported. Evidence for the association of ALS and
      diabetes mellitus is limited. We aimed to assess the overall and age- and sex
      specific risks of ALS among patients with diabetes in Taiwan. METHODS: The study
      cohort included 615 492 diabetic patients and 614 835 age- and sex-matched
      subjects as a comparison cohort, followed from 2000 to 2008. We estimated the
      incidence densities of ALS and calculated the relative hazard ratios (HRs) of ALS
      (ICD-9-CM 335.20) in relation to diabetes using a Cox proportional hazard
      regression model, with adjustment for potential confounders, including sex, age,
      geographic area, urbanization status, Charlson Comorbidity Index, frequency of
      medical visit, and histories of hypertension, hyperlipidemia, and chronic
      obstructive pulmonary disease. RESULTS: Over a 9-year period, 255 diabetic and
      201 non-diabetic subjects developed ALS, corresponding to incidence densities of
      7.42 and 5.06 per 100 000 person-years, respectively. After adjustment for
      potential confounders, patients with diabetes experienced a significantly
      elevated HR of 1.35 (95% confidence interval [CI], 1.10-1.67). A higher covariate
      adjusted HR was noted in men (HR 1.48; 95% CI, 1.13-1.94) than in women (HR 1.17;
      95% CI, 0.84-1.64), while men aged <=65 years showed the most increased HR of
      1.67 (95% CI, 1.18-2.36). CONCLUSIONS: This study demonstrated a moderate but
      significant association of diabetes with ALS onset, and such association is not
      confounded by socio-demographic characteristics or certain ALS-related co
      morbidities. Further studies are warranted to examine whether the findings
      observed in our study can be replicated.

PMID- 25947581
TI  - Association Between Average Daily Television Viewing Time and Chronic Obstructive
      Pulmonary Disease-Related Mortality: Findings From the Japan Collaborative Cohort
      Study.
AB  - BACKGROUND: Sedentary behavior is associated with cardiovascular disease,
      diabetes mellitus, and cancer morbidity, and watching television (TV) is an
      important sedentary behavior. The aim of this study is to clarify the association
      between TV viewing time and chronic obstructive pulmonary disease (COPD)-related
      mortality in Japanese adults. METHODS: Using the Cox proportional hazard model,
      we assessed COPD-related mortality by TV viewing time in a national cohort of 33
      414 men and 43 274 women without cancer, stroke, myocardial infarction, or
      tuberculosis at baseline (1988-1990). RESULTS: The median follow-up was 19.4
      years; 244 men and 34 women died of COPD. Men watching >=4 hours/day of TV were
      more likely to die of COPD than those watching <2 hours/day (hazard ratio 1.63;
      95% confidence interval, 1.04-2.55), independent of major confounders. No
      association was found in women. CONCLUSIONS: Avoiding a sedentary lifestyle,
      particularly prolonged TV viewing, may help in preventing death from COPD among
      men.

PMID- 25947582
TI  - Quality of life, social impact and functional outcome following ileal pouch-anal
      anastomosis for ulcerative colitis and familial adenomatous polyposis.
AB  - This study aims to assess quality of life (QoL), functional outcome, and social
      impact following ileal pouch anal anastomosis (IPAA) for ulcerative colitis (UC)
      and familial adenomatous polyposis (FAP) since Indian data is limited. Data was
      collected prospectively from patients who underwent IPAA for UC or FAP from 2004
      to 2013. QoL and functional outcome at 1, 3, and 5 years after surgery, return to
      work, and change of job (social impact) were documented. QoL was assessed using
      the validated Cleveland Global Quality of Life (CGQL) score, the normal score
      being 1.0. Twenty-five patients were analyzed. Mean CGQL scores before surgery
      and at 1, 3, and 5 years were 0.5, 0.63, 0.73, and 0.8, respectively. FAP
      patients had better scores at 3 and 5 years. Only 40 % returned to same job.
      Sixty-four percent returned to work within a year. The median number of bowel
      movements per 24 h was less for FAP patients at 3 and 5 years. UC patients on
      long-term steroids had poorer function at 3 years. Long-term QoL and functional
      outcomes following IPAA are acceptable. Initial deterioration in QoL, mainly in
      FAP and long-term adverse social impact in both groups should not be
      underestimated. UC patients on long-term steroids showed delayed improvement in
      pouch function.

PMID- 25947583
TI  - Did the Health Research Act turn out as intended?

PMID- 25947584
TI  - Research ethics - a perennial topic of discussion.

PMID- 25947585
TI  - [Confidential data and research ethics].

PMID- 25947586
TI  - [Re: Special outpatient clinic for skeletal dysplasias].

PMID- 25947587
TI  - [Re: A man in his 60s that unexpectedly and dramatically attempts suicide].

PMID- 25947588
TI  - [M. Holm replies].

PMID- 25947589
TI  - [Clinical benefits of platelet-rich plasma?].

PMID- 25947590
TI  - Flawed recommendation issued by the Norwegian Directorate of Health concerning
      the determination of fetal age.

PMID- 25947591
TI  - [An announcement of concern about antibiotics in chicken feed].

PMID- 25947592
TI  - [We do not want more pills].

PMID- 25947593
TI  - [ECG in general practice--the quality can be improved].

PMID- 25947596
TI  - Research findings with clinical implications.
AB  - BACKGROUND: Medical and health research may yield findings that are of direct
      clinical significance for project participants. The Council of Europe has stated
      that information on such findings shall be offered to participants, and that
      applications to research ethics committees shall include plans for managing such
      findings. The purpose of the study was to investigate how the management of such
      findings had been described in research projects that had been granted prior
      approval by a regional committee for medical and health research ethics (REK).
      MATERIAL AND METHOD: Research projects that were associated with Oslo University
      Hospital and had a start-up date in 2011 were identified in the database of the
      regional ethics committee. Copies of the application form submitted to the
      committee, project protocols, participant information/consent forms and letters
      of approval were reviewed with regard to information on the management of
      findings with possible clinical implications. RESULTS: Of the 87 projects found
      in the database, 70 were included in the study. Of these, 57 studies involved
      direct interaction with humans, whereof 45 with intended use of biological
      material. In 21 studies, the management of findings with possible clinical
      implications was described in one or more documents. In all of these projects,
      the applicant him-/herself had referred to this topic in the initial application.
      INTERPRETATION: The absence of written information on the management of research
      findings with possible clinical implications is not in conformity with the
      recommendations issued by the Council of Europe. By introducing a separate item
      for this in the form to be submitted to the regional ethics committee for
      application of prior approval, this issue could be made subject to better
      assessment.

PMID- 25947597
TI  - Infections in traumatic wounds sutured at a Norwegian Accident and Emergency
      Department.
AB  - BACKGROUND: Different countries have different wound treatment traditions. We
      have studied the incidence and different factors related to infections in wound
      injuries sutured at a Norwegian A&E department. METHOD: In this prospective
      study, clinical data were collected on 102 patients with traumatic wound injuries
      treated with sutures at Bergen Accident and Emergency Department between 30
      February 2011 and 30 June 2011. Any wound infections in 97 of these patients at
      the time of suture removal were assessed and classified according to severity on
      a scale of grade 0 to grade 4. RESULTS: There were no serious infections, but
      mild clinical wound infections occurred in 15% of patients: 11% grade 1 and 4%
      grade 2 infections. Patients less than 65 years old had often cut themselves with
      knives (n = 33, 37%), and on their hands (n = 60, 67%), Men were most frequently
      injured at work (n = 38, 54%) and women most often at home (n = 18, 56%). No
      statistically significant correlation was found between the incidence of wound
      infections and the length of the wound, the time elapsed before suturing, the
      wound's location on the body, contamination or underlying chronic diseases. Two
      of the three self-inflictors in our study had clinical wound infections. Half of
      the bacteriological samples from ten of 15 wounds with clinical infection had
      plentiful growth of Staphylococcus aureus. One patient received oral antibiotic
      treatment for wound infection, and two had local antibiotic treatment.
      INTERPRETATION: Mild clinical infections were found in almost one of six wounds
      sutured at a Norwegian A&E department. More studies are necessary to provide
      basic data to enable targeted improvements in wound treatment in the primary
      healthcare service.

PMID- 25947598
TI  - [A man in his 30s with diabetes and vitiligo].

PMID- 25947599
TI  - Data quality in the Causes of Death Registry.

PMID- 25947600
TI  - [Hospital routines and traumatization of patients].

PMID- 25947601
TI  - [Traumatization of patients in hospitals].

PMID- 25947602
TI  - [When we talk about genes].

PMID- 25947613
TI  - A coumarin dimer probe of mechanochemical scission efficiency in the sonochemical
      activation of chain-centered mechanophore polymers.
AB  - Here we present a coumarin dimer (CD) mechanophore that, when embedded near the
      mid-chain of poly(methyl acrylate) polymers, activates under pulsed ultrasound
      conditions to yield coumarin chain-end functional polymers. Quantitative
      photochemical scission of the CD polymers provides a reference against which the
      activation efficiency of chain-centered mechanophores in polymers synthesized by
      controlled/living radical polymerization (CRP) can be assessed. Activation
      efficiency is characterized with respect to the polymer molecular weight (MW),
      polydispersity index (PDI), and distribution of mechanophores along the backbone.

PMID- 25947616
TI  - White-light induced grafting of 3-MPA on the Si(111)-H surface for catalyzing Au
      nanoparticles' in situ growth.
AB  - A novel, mild and effective method was designed for grafting of high-quality
      organic monolayers on a silicon surface to catalyze nanoparticles' growth. By
      using a white-light source, 3-mercaptopropionic acid (3-MPA) molecules were
      attached to hydrogen-terminated Si(111) surfaces at room temperature. The
      attached monolayers were characterized using X-ray photoelectron spectroscopy to
      provide detailed information. The in situ growth of Au nanoparticles (AuNPs) with
      dimensions below 20 nm was catalyzed on a silicon surface with highly uniform and
      compact structure morphology. The AuNPs can grow selectively in a certain region
      on a patterned Si-Si3N4 chip. p-Nitrothiophenol (p-NTP) was used as the probe to
      evaluate the SERS enhancement of the highly uniform and compact AuNP-Si
      substrate. In order to better understand the white light initiation of the
      addition reaction of 3-MPA on the Si(111)-H surface, the mechanism was elucidated
      by density functional theoretical (DFT) calculations, which indicated that the
      formation of the Si-O bond occurred at the PEC of the first singlet excited state
      (S1) with a very low activation barrier about 30% of the ground state (S0) value.

PMID- 25947614
TI  - Safety and efficacy of osteotomies in adult spinal deformity: what happens in the
      first year?
AB  - PURPOSE: Spinal surgery for adult spinal deformity (ASD) may require the use of
      osteotomies, which may have high complication rates (up to 80 %). These may be
      expected to affect health-related quality of life (HRQOL) in the early
      postoperative phase but little is known about the clinical course of these
      patients in the first year following surgery. The aim of the study is to evaluate
      the radiological results and HRQOL in patients undergoing a spinal osteotomy for
      ASD within the first year following surgery with special reference to the effect
      of complications. METHODS: From a prospective multicenter ASD database, patients
      who had undergone a Smith-Petersen osteotomy (SPO), pedicle substraction
      osteotomy (PSO), vertebral column resection (VCR) or any combination of these
      were reviewed for radiological sagittal alignment parameters [sagittal vertical
      axis (SVA), global tilt, lumbar lordosis, T2-sagittal tilt (ST)] as well as HRQOL
      [Oswestry Disability Index (ODI), short form-36 items (SF-36) Physical Component
      Score (PCS), SF-36 mental CS (MCS), Scoliosis Research Society (SRS)-22
      questionnaire (SRS-22) subtotal] preoperatively and at the 6th- and 12th-month
      follow-ups with special reference to complications classified as major (life
      threatening or requiring additional surgery) and minor and their effects on
      HRQOL. RESULTS: 121 patients (85 F, 36 M) with a total of 71 SPOs, 45 PSOs and 13
      VCRs were evaluated. Osteotomy resulted in correction of the major coronal Cobb
      angle from 43.0 +/- 3.7 degrees  to 24.8 +/- 2.8 degrees  (p < 0.001) and the SVA
      from 69.0 +/- 10.3 to 52.4 +/- 6.6 mm (p = 0.001). Other radiological parameters
      showed no significant changes. Remarkable improvements in HRQOL scores with a
      strong age effect (p <= 0.01), for all instruments except SF-36 MCS, were found.
      Most of these HRQOL improvements have been achieved within the first 6 months. A
      total of 114 complications (59 major, 55 minor) that had a lesser effect on the
      age-adjusted HRQOL scores (p < 0.05) (except for the SF-36 PCS) and 1 death were
      observed. CONCLUSIONS: Osteotomies were moderately effective in radiological
      improvement but resulted in a significant increase in HRQOL. They were associated
      with a high rate of complications but these had no/minimal effect on the clinical
      outcome. Contrary to the general perception, the greatest improvements in HRQOL
      were seen to take place during the first 6 months after surgery, even in the
      presence of complications.

PMID- 25947617
TI  - Molecular Characterization of a Recombinant Zea mays Phenylalanine Ammonia-Lyase
      (ZmPAL2) and Its Application in trans-Cinnamic Acid Production from L
      Phenylalanine.
AB  - Phenylalanine ammonia-lyase (PAL) is one of the most extensively studied enzymes
      with its crucial role in secondary phenylpropanoid metabolism of plants.
      Recently, its demand has been increased for aromatic chemical production, but its
      applications in trans-cinnamic acid production were not much explored. In the
      present study, a putative PAL gene from Zea mays designated as ZmPAL2 was
      expressed and characterized in Escherichia coli BL21 (DE3). The recombinant
      ZmPAL2 exhibited a high PAL activity (7.14 U/mg) and a weak tyrosine ammonia
      lyase activity. The optimal temperature of ZmPAL2 was 55  degrees C, and the
      thermal stability results showed that about 50 % of enzyme activity remained
      after a treatment at 60  degrees C for 6 h. The recombinant ZmPAL2 is a good
      candidate for the production of trans-cinnamic acid. The vitro conversion
      indicated that the recombinant ZmPAL2 could effectively catalyze the L
      phenylalanine to trans-cinnamic acid, and the trans-cinnamic acid concentration
      can reach up to 5 g/l. 

PMID- 25947618
TI  - Integrated Production of Xylonic Acid and Bioethanol from Acid-Catalyzed Steam
      Exploded Corn Stover.
AB  - High-efficiency xylose utilization is one of the restrictive factors of
      bioethanol industrialization. However, xylonic acid (XA) as a new bio-based
      platform chemical can be produced by oxidation of xylose with microbial. So, an
      applicable technology of XA bioconversion was integrated into the process of
      bioethanol production. After corn stover was pretreated with acid-catalyzed steam
      explosion, solid and liquid fractions were obtained. The liquid fraction, also
      named as acid-catalyzed steam-exploded corn stover (ASC) prehydrolyzate (mainly
      containing xylose), was catalyzed with Gluconobacter oxydans NL71 to prepare XA.
      After 72 h of bioconversion of concentrated ASC prehydrolyzate (containing 55.0
      g/L of xylose), the XA concentration reached a peak value of 54.97 g/L, the sugar
      utilization ratio and XA yield were 94.08 and 95.45 %, respectively. The solid
      fraction was hydrolyzed to produce glucose with cellulase and then fermented with
      Saccharomyces cerevisiae NL22 to produce ethanol. After 18 h of fermentation of
      concentrated enzymatic hydrolyzate (containing 86.22 g/L of glucose), the ethanol
      concentration reached its highest value of 41.48 g/L, the sugar utilization ratio
      and ethanol yield were 98.72 and 95.25 %, respectively. The mass balance showed
      that 1 t ethanol and 1.3 t XA were produced from 7.8 t oven dry corn stover.

PMID- 25947619
TI  - A Nucleic Acid Biosensor for Detection of Hepatitis C Virus Genotype 1a Using
      Poly(L-Glutamic Acid)-Modified Electrode.
AB  - An electrochemical nucleic acid biosensor based on label-free DNA detection
      method was prepared for the first time by using electropolymerized poly(L
      glutamic acid)-modified pencil graphite electrode (PGA/PGE) for detection of
      hepatitis C virus genotype 1a (HCV1a). Inosine-substituted 20-mer probes related
      to the HCV1a were immobilized onto PGA/PGE surface by covalent linking with the
      formation of amide bonds. Square wave voltammetry (SWV) was used to monitor the
      oxidation signal of guanine in the hybridization events, which gave an oxidation
      peak at +1.05 V. An increase in the oxidation signal of guanine was showed by
      hybridization of the probe with the complementary DNA. Noncomplementary
      oligonucleotides were also used to investigate the selectivity of the biosensor.
      The proposed nucleic acid biosensor was linear in the range of 50 nM to 1.0 MUM,
      exhibiting a limit of detection of 40.6 nM. Finally, single-stranded synthetic
      PCR product analogues of HCV1a were performed in optimal condition. This PGA
      modified nucleic acid sensor is cost-effective and disposable, and besides, it
      has superior electrocatalytic effect on the oxidation of guanine.

PMID- 25947620
TI  - Interactions Between Autotrophic and Heterotrophic Strains Improve CO2 Fixing
      Efficiency of Non-photosynthetic Microbial Communities.
AB  - Five autotrophic strains isolated from non-photosynthetic microbial communities
      (NPMCs), which were screened from oceans with high CO2 fixing capability, were
      identified as Ochrobactrum sp. WH-2, Stenotrophomonas sp. WH-11, Ochrobactrum sp.
      WH-13, Castellaniella sp. WH-14, and Sinomicrobium oceani WH-15. The CO2 fixation
      pathways of all these strains were Calvin-Benson-Bassham pathway. These strains
      could metabolize multifarious organic compounds, which allowed switching them to
      autotrophic culture after enrichment in heterotrophic culture. The central
      composite response surface method indicated that these strains possessed many
      interactive effects, which increased the CO2 fixing efficiency of a combined
      community composed of these strains by 56 %, when compared with that of the
      single strain. Furthermore, another combined community composed of these
      autotrophic strains and NPMC had richer interactive relationships, with CO2
      fixing efficiency being 894 % higher than that of the single strain and 148 %
      higher than the theoretical sum of the CO2 fixing efficiency of each of its
      microbial components. The interaction between strictly heterotrophic bacteria in
      NPMC and isolated autotrophic strains played a crucial role in improving the CO2
      fixing efficiency, which not only eliminated self-restraint of organic compounds
      generated during the growth of autotrophic bacteria but also promoted its
      autotrophic pathway.

PMID- 25947621
TI  - Competence and the Evolutionary Origins of Status and Power in Humans.
AB  - In this paper I propose an evolutionary model of human status that expands upon
      an earlier model proposed by Henrich and Gil-White Evolution and Human Behavior,
      22,165-196 (2001). According to their model, there are two systems of status
      attainment in humans-"two ways to the top": the dominance route, which involves
      physical intimidation, a psychology of fear and hubristic pride, and provides
      coercive power, and the prestige route, which involves skills and knowledge
      (competence), a psychology of attraction to experts and authentic pride, and
      translates mainly into influence. The two systems would have evolved in response
      to different selective pressures, with attraction to experts serving a social
      learning function and coinciding with the evolution of cumulative culture. In
      this paper I argue that (1) the only one way to the top is competence because
      dominance itself involves competence and confers prestige, so there is no such
      thing as pure dominance status; (2) dominance in primates has two components: a
      competitive one involving physical coercion and a cooperative one involving
      competence-based attraction to high-ranking individuals (proto-prestige); (3)
      competence grants the same general type of power (dependence-based) in humans and
      other primates; (4) the attractiveness of high rank in primates is homologous
      with the admiration of experts in humans; (5) upon the evolution of cumulative
      culture, the attractiveness of high rank was co-opted to generate status
      differentials in a vast number of culturally generated domains of activity. I
      also discuss, in this perspective, the origins of hubristic pride, authentic
      pride, and nonauthoritarian leadership. 

PMID- 25947622
TI  - Venous thromboembolism: "... an ounce of prevention is worth a pound of cure".

PMID- 25947623
TI  - pH-Induced processes in wire-like multichromophoric homo- and heterotrimetallic
      complexes of Fe(II), Ru(II), and Os(II).
AB  - In this work we studied the influence of pH on the absorption, steady state and
      time-resolved emission spectroscopic behaviors of recently reported
      multichromophoric trimetallic complexes of the forms [(bpy)2M(phen-Hbzim
      tpy)M'(tpy-Hbzim-phen)M(bpy)2](6+) (M = Ru(II) or Os(II), and M' = Fe(II),
      Ru(II), and Os(II)) derived from a heteroditopic phenanthroline-terpyridine
      bridge, 2-(4-(2,6-di(pyridin-2-yl)pyridine-4-yl)phenyl)-1H-imidazole[4,5
      f][1,10]phenanthroline (tpy-Hbzim-phen) and 2,2'-bipyridine (bpy) as the
      auxiliary ligand. For purposes of comparison, the UV-vis absorption and emission
      titrations of three monometallic model compounds [(bpy)2Ru(phen-Hbzim
      tpy)](ClO4)2 (1), [(bpy)2Os(phen-Hbzim-tpy)] (ClO4)2 (2) and [(tpy-PhCH3)Ru(tpy
      Hbzim-phen)](ClO4)2 (3), where tpy-PhCH3 = 4'-(4-methylphenyl)-2,2':6',2''
      terpyridine) were studied under the same experimental conditions. The absorption
      titration data were used to determine the ground state pKa values, whereas the
      luminescence and lifetime data were utilized for the determination of excited
      state pKa* values of the complexes. The evolving factor analyses of the set of
      absorption spectra of the complexes obtained by varying the pH of the solution
      confirm that only three absorbing species exist in the pH window of 2-12.
      Moreover, the modulation of the rate of the intramolecular energy transfer among
      the components in the homo- and heterotrimetallic complexes as a function of pH
      of the solution was also demonstrated.

PMID- 25947624
TI  - CMTX1 patients' cells present genomic instability corrected by CamKII inhibitors.
AB  - BACKGROUND: We previously described that fibroblasts from animal models of CMTX1
      present genomic instability and poor connexon activity. In vivo, these transgenic
      mice present motor deficits. This phenotype could be significantly reverted by
      treatment with (CamKII) inhibitors. The objective of this study is to translate
      our findings to patients. METHODS: We cultured fibroblasts from skin biopsies of
      CMTX1 patients and analyzed cells for genomic instabilty, connexon activity, and
      potential correction by CamKII inhibitors. RESULTS: The phenotypic analysis of
      these cells confirmed strong similarities between the GJB1 transgenic mouse cell
      lines and CMTX1 patient fibroblast cell lines. Both present mitotic anomalies,
      centrosome overduplication, and connexon activity deficit. This phenotype is
      corrected by CamKII inhibitors. CONCLUSIONS: Our data demonstrate that
      fibroblasts from CMTX1 patients present a phenotype similar to transgenic lines
      that can be corrected by CamKII inhibitors. This presents a track to develop
      therapeutic strategies for CMTX1 treatment.

PMID- 25947626
TI  - Role of moesin in HMGB1-stimulated severe inflammatory responses.
AB  - Sepsis is a life-threatening condition that arises when the body's response to
      infection causes systemic inflammation. High-mobility group box 1 (HMGB1), as a
      late mediator of sepsis, enhances hyperpermeability, and it is therefore a
      therapeutic target. Despite extensive research into the underlying mechanisms of
      sepsis, the target molecules controlling vascular leakage remain largely unknown.
      Moesin is a cytoskeletal protein involved in cytoskeletal changes and
      paracellular gap formation. The objectives of this study were to determine the
      roles of moesin in HMGB1-mediated vascular hyperpermeability and inflammatory
      responses and to investigate the mechanisms of action underlying these responses.
      Using siRNA knockdown of moesin expression in primary human umbilical vein
      endothelial cells (HUVECs), moesin was found to be required in HMGB1-induced F
      actin rearrangement, hyperpermeability, and inflammatory responses. The
      mechanisms involved in moesin phosphorylation were analysed by blocking the
      binding of the HMGB1 receptor (RAGE) and inhibiting the Rho and MAPK pathways.
      HMGB1-treated HUVECs exhibited an increase in Thr558 phosphorylation of moesin.
      Circulating levels of moesin were measured in patients admitted to the intensive
      care unit with sepsis, severe sepsis, and septic shock; these patients showed
      significantly higher levels of moesin than healthy controls, which was strongly
      correlated with disease severity. High blood moesin levels were also observed in
      cecal ligation and puncture (CLP)-induced sepsis in mice. Administration of
      blocking moesin antibodies attenuated CLP-induced septic death. Collectively, our
      findings demonstrate that the HMGB1-RAGE-moesin axis can elicit severe
      inflammatory responses, suggesting it to be a potential target for the
      development of diagnostics and therapeutics for sepsis. 

PMID- 25947625
TI  - MicroRNA-572 expression in multiple sclerosis patients with different patterns of
      clinical progression.
AB  - BACKGROUND: Demyelination and failure of remyelination are core mechanisms in the
      pathogenesis of multiple sclerosis (MS); the factor(s) modulating these processes
      are still mostly unknown. MicroRNA 572 (miR-572) is deregulated in MS and is
      suggested to targets neural cell adhesion molecule (NCAM), a glycoprotein
      involved in CNS reparative mechanisms. The aim of this study is to analyze miR
      572 in patients with different clinical phenotypes of MS. METHODS: qPCR
      quantification of miR-572 isolated from serum was performed in 16 primary
      progressive (PP), 15 secondary progressive (SP), 31 relapsing remitting (RR) MS
      patients and 15 sex-and age-matched healthy controls. RESULTS: miR-572 expression
      was reduced overall in MS patients (p < 0.05) compared to HC; this miRNA was
      significantly upregulated in SPMS and in RRMS during disease relapse, whereas it
      was downregulated in PPMS and in quiescent phases of RRMS. miR-572 expression
      correlated with EDSS scores (RSp = 0.491; p < 0.05) independently of the clinical
      phenotype. The results suggest that this miRNA might be a tool that helps
      distinguishing between PPMS and SPMS and between relapsing and remitting phases
      in RRMS. CONCLUSIONS: Evaluation of miR-572 may serve as a non-invasive biomarker
      for remyelination.

PMID- 25947627
TI  - An upconversion luminescence nanoprobe for the ultrasensitive detection of
      hyaluronidase.
AB  - A new upconversion luminescence nanoprobe for the detection of hyaluronidase has
      been developed by coupling the hyaluronic acid-bearing upconversion fluorescence
      nanoparticles (HA-UCNPs) with poly(m-phenylenediamine) (PMPD) nanospheres via
      covalent linkage. The nanoprobe alone exhibits an extremely low background signal
      owing to the effective fluorescence quenching by electron-rich PMPD and the near
      infrared excitation characteristic (lambdaex = 980 nm) of HA-UCNPs; upon reaction
      with hyaluronidase, however, a more than 31-fold fluorescence enhancement is
      produced. Compared with the corresponding nanosystem assembled via physical
      adsorption, the prepared nanoprobe shows a largely increased stability and a much
      higher signal-to-background ratio, which offers an ultrasensitive assay for
      hyaluronidase, with a detection limit of 0.6 ng/mL. The nanoprobe has been
      successfully used to determine hyaluronidase in human serum samples from both
      colorectal cancer patients and healthy people, disclosing that the serum
      hyaluronidase level in colorectal cancer patients is roughly 3 times higher than
      that in healthy people. Furthermore, the nanoprobe has also been employed to
      study the activity change of hyaluronidase affected by different concentrations
      of arsenate (a potential carcinogen), and the results show that even a low dosage
      of arsenate (50 MUg/L) can raise the activity of hyaluronidase by about one
      third, revealing the relationship between arsenate and the enzyme. The proposed
      method is not only simple but also highly sensitive, making it useful to assay
      hyaluronidase in relevant clinical samples. 

PMID- 25947628
TI  - Site-specific deposition of single gold nanoparticles by individual growth in
      electrohydrodynamically-printed attoliter droplet reactors.
AB  - Gold nanoparticles with unique electronic, optical and catalytic properties can
      be efficiently synthesized in colloidal suspensions and are of broad scientific
      and technical interest and utility. However, their orderly integration on
      functional surfaces and devices remains a challenge. Here we show that single
      gold nanoparticles can be directly grown in individually printed, stabilized
      metal-salt ink attoliter droplets, using a nanoscale electrohydrodynamic printing
      method with a stable high-frequency dripping mode. This enables controllable
      sessile droplet nanoreactor formation and sustenance on non-wetting substrates,
      despite simultaneous rapid evaporation. The single gold nanoparticles can be
      formed inside such reactors in situ or by subsequent thermal annealing and plasma
      ashing. With this non-contact technique, single particles with diameters tunable
      in the range of 5-35 nm and with narrow size distribution, high yield and
      alignment accuracy are generated on demand and patterned into arbitrary arrays.
      The nanoparticles feature good catalytic activity as shown by the exemplary
      growth of silicon nanowires from the nanoparticles and the etching of nanoholes
      by the printed nanoparticles. 

PMID- 25947629
TI  - Suicide, Self-Mutilation and Delirium Tremens.

PMID- 25947631
TI  - Streamlining educational provision for cardiovascular nurses: A beginning not an
      end.

PMID- 25947630
TI  - Integrated digital inverters based on two-dimensional anisotropic ReS2 field
      effect transistors.
AB  - Semiconducting two-dimensional transition metal dichalcogenides are emerging as
      top candidates for post-silicon electronics. While most of them exhibit isotropic
      behaviour, lowering the lattice symmetry could induce anisotropic properties,
      which are both scientifically interesting and potentially useful. Here we present
      atomically thin rhenium disulfide (ReS2) flakes with unique distorted 1T
      structure, which exhibit in-plane anisotropic properties. We fabricated monolayer
      and few-layer ReS2 field-effect transistors, which exhibit competitive
      performance with large current on/off ratios (~10(7)) and low subthreshold swings
      (100 mV per decade). The observed anisotropic ratio along two principle axes
      reaches 3.1, which is the highest among all known two-dimensional semiconducting
      materials. Furthermore, we successfully demonstrated an integrated digital
      inverter with good performance by utilizing two ReS2 anisotropic field-effect
      transistors, suggesting the promising implementation of large-scale two
      dimensional logic circuits. Our results underscore the unique properties of two
      dimensional semiconducting materials with low crystal symmetry for future
      electronic applications. 

PMID- 25947632
TI  - Web-based textual analysis of free-text patient experience comments from a survey
      in primary care.
AB  - BACKGROUND: Open-ended questions eliciting free-text comments have been widely
      adopted in surveys of patient experience. Analysis of free text comments can
      provide deeper or new insight, identify areas for action, and initiate further
      investigation. Also, they may be a promising way to progress from documentation
      of patient experience to achieving quality improvement. The usual methods of
      analyzing free-text comments are known to be time and resource intensive. To
      efficiently deal with a large amount of free-text, new methods of rapidly
      summarizing and characterizing the text are being explored. OBJECTIVE: The aim of
      this study was to investigate the feasibility of using freely available Web-based
      text processing tools (text clouds, distinctive word extraction, key words in
      context) for extracting useful information from large amounts of free-text
      commentary about patient experience, as an alternative to more resource intensive
      analytic methods. METHODS: We collected free-text responses to a broad, open
      ended question on patients' experience of primary care in a cross-sectional
      postal survey of patients recently consulting doctors in 25 English general
      practices. We encoded the responses to text files which were then uploaded to
      three Web-based textual processing tools. The tools we used were two text cloud
      creators: TagCrowd for unigrams, and Many Eyes for bigrams; and Voyant Tools, a
      Web-based reading tool that can extract distinctive words and perform Keyword in
      Context (KWIC) analysis. The association of patients' experience scores with the
      occurrence of certain words was tested with logistic regression analysis. KWIC
      analysis was also performed to gain insight into the use of a significant word.
      RESULTS: In total, 3426 free-text responses were received from 7721 patients
      (comment rate: 44.4%). The five most frequent words in the patients' comments
      were "doctor", "appointment", "surgery", "practice", and "time". The three most
      frequent two-word combinations were "reception staff", "excellent service", and
      "two weeks". The regression analysis showed that the occurrence of the word
      "excellent" in the comments was significantly associated with a better patient
      experience (OR=1.96, 95%CI=1.63-2.34), while "rude" was significantly associated
      with a worse experience (OR=0.53, 95%CI=0.46-0.60). The KWIC results revealed
      that 49 of the 78 (63%) occurrences of the word "rude" in the comments were
      related to receptionists and 17(22%) were related to doctors. CONCLUSIONS: Web
      based text processing tools can extract useful information from free-text
      comments and the output may serve as a springboard for further investigation.
      Text clouds, distinctive words extraction and KWIC analysis show promise in quick
      evaluation of unstructured patient feedback. The results are easily
      understandable, but may require further probing such as KWIC analysis to
      establish the context. Future research should explore whether more sophisticated
      methods of textual analysis (eg, sentiment analysis, natural language processing)
      could add additional levels of understanding.

PMID- 25947634
TI  - Long-term effect of a name change for schizophrenia on reducing stigma.
AB  - BACKGROUND: A name change for schizophrenia was first implemented in Japan for
      reducing stigma in 2002; however, little is known of its long-term impact.
      METHODS: Total 259 students from 20 universities answered an anonymous self
      administered questionnaire about their mental health-related experiences, and
      stigma scales including feasible knowledge and negative stereotypes for four
      specific diseases, including schizophrenia (old and new names), depression, and
      diabetes mellitus. We also asked to choose the old and new names of schizophrenia
      and dementia among ten names for mental and physical illnesses and conditions.
      RESULTS: The participants had more feasible knowledge and fewer negative
      stereotypes for the new name of schizophrenia than the old name, but were still
      significantly worse than for depression and diabetes mellitus (p < 0.01). Direct
      contact experiences with those who have mental health problems were associated
      with feasible knowledge for schizophrenia but not negative stereotypes (beta =
      0.13, p = 0.020). The rate of correct responses for the old and new names of
      schizophrenia was significantly lower than that of dementia (41 vs. 87%, p <
      0.001). Mental health-related experience from media was associated with the
      recognition of name change for schizophrenia (p = 0.008), which was associated
      with less feasible knowledge for new name of schizophrenia. DISCUSSION: The name
      change of schizophrenia has reduced stigma since 12 years have passed. More
      effective campaigns, educational curricula, and policy making are needed to
      reduce stigma toward schizophrenia.

PMID- 25947635
TI  - The incremental burden of pain in patients with depression: results of a Japanese
      survey.
AB  - BACKGROUND: Major depressive disorder (MDD) is a chronic mental illness which
      affects an estimated 3% of the Japanese population. Many patients with MDD report
      painful physical symptoms, and research outside of Japan suggests such patients
      may represent a subtype of depression which is more severe and difficult to
      treat. There is no evidence available about the characteristics or incremental
      burden of these patients in Japan. The objective of this study was to quantify
      the incremental burden of physical pain among individuals in Japan diagnosed with
      depression. METHODS: Data for individuals age 18 and older who reported a
      physician diagnosis of depression were obtained from the Japan National Health
      and Wellness Survey (NHWS). Respondents who also reported physical pain were
      matched to respondents who did not report pain using propensity scores and
      compared using bivariate statistics. Measures included Patient Health
      Questionnaire (PHQ-9) for depression severity, Medical Outcomes Study 12-Item
      Short Form Survey Instrument (SF-12v2) for health-related quality of life, the
      Work Productivity and Activity Impairment (WPAI) for work and activity
      impairment, and 6-month report of health care use. RESULTS: Individuals with
      depression who reported physical pain had higher PHQ-9 depression scores (14.3
      vs. 11.1, p<0.001), lower health-related quality of life (Mental Component
      Summary score [MCS] 29.1 vs. 32.0, p<0.01; Physical Component Summary score [PCS]
      43.0 vs. 47.2, p<0.001; health utility [SF-6D] 0.567 vs. 0.613, p<0.001), more
      presenteeism (46.3% vs. 36.8%, p<0.01), more overall work impairment (51.4% vs.
      42.3%, p<0.01), more activity impairment (55.4% vs. 43.9%, p<0.001), and reported
      using more health care provider visits in the prior 6 months (17.7 vs. 12.8,
      p<0.01) as well as hospitalizations (1.7 vs. 0.8, p<0.05) relative to propensity
      score matched controls without pain. Absenteeism (13.1% vs. 11.4%, p=0.51) and
      emergency room visits (0.31 vs. 0.35, p=0.76) were not significantly different
      between the two matched groups. CONCLUSIONS: Individuals whose depression is
      accompanied by physical pain have a higher burden of illness than those whose
      depression does not include physical pain. Clinicians should take the presence of
      pain into account and consider treating both the physical and emotional symptoms
      of these patients.

PMID- 25947636
TI  - Vancomycin in the treatment of methicillin-resistant Staphylococcus aureus - a
      clinician's guide to the science informing current practice.
AB  - Clinicians treating an infection assess a patient in terms of disease
      manifestation, causative organism and available antibiotic options with the aim
      of devising a therapeutic strategy under the creed of 'first, do no harm'. It is
      often only when treatment is failing or options are limited, as in the scenario
      of multidrug-resistant organisms, that consideration is given to the interplay
      that occurs between the microbe and the host. The emergence of Staphylococcus
      aureus with reduced susceptibility to vancomycin provides a prime example of
      these dynamic interactions. This review shall explore these concepts in relation
      to vancomycin for the treatment of methicillin-resistant S. aureus, with the aim
      of providing an informed approach to the utilization of this drug. 

PMID- 25947637
TI  - Competition between recombination and extraction of free charges determines the
      fill factor of organic solar cells.
AB  - Among the parameters that characterize a solar cell and define its power
      conversion efficiency, the fill factor is the least well understood, making
      targeted improvements difficult. Here we quantify the competition between charge
      extraction and recombination by using a single parameter theta, and we
      demonstrate that this parameter is directly related to the fill factor of many
      different bulk-heterojunction solar cells. Our finding is supported by
      experimental measurements on 15 different donor:acceptor combinations, as well as
      by drift-diffusion simulations of organic solar cells in which charge-carrier
      mobilities, recombination rate, light intensity, energy levels and active-layer
      thickness are all varied over wide ranges to reproduce typical experimental
      conditions. The results unify the fill factors of several very different
      donor:acceptor combinations and give insight into why fill factors change so much
      with thickness, light intensity and materials properties. To achieve fill factors
      larger than 0.8 requires further improvements in charge transport while reducing
      recombination. 

PMID- 25947638
TI  - Novel surgical options for gastroesophageal reflux disease.
AB  - There are limited options to patients with gastroesophageal reflux disease (GERD)
      who are not satisfied with acid suppression therapy. Fundoplication, the standard
      surgical procedure for GERD, is effective but is associated with adverse side
      effects and has thus been performed less frequently, creating a need for
      alternative surgical interventions that are effective, yet less invasive and
      reversible. Lately, two such interventions were developed: the magnetic sphincter
      augmentation and electrical stimulation of the lower esophageal sphincter. Human
      studies describing safety and efficacy over a follow-up period of a number of
      years have been published, documenting efficacy and safety of these
      interventions. Future studies should clarify the role of these procedures in the
      spectrum of GERD therapy. 

PMID- 25947640
TI  - Treatment of negative dysphotopsia with supplementary implantation of a sulcus
      fixated intraocular lens.
AB  - PURPOSE: Our aim was to evaluate the resolution of negative dysphotopsia after
      supplementary implantation of a sulcus-fixated intraocular lens (IOL). METHODS:
      This was a retrospective case series. Patients with severe negative dysphotopsia
      were treated with supplementary implantation of the Rayner Sulcoflex Aspheric
      (653 L) IOL. Primary outcome measurements were subjectively reported complaints
      of dysphotopsia, best corrected distance visual acuity (CDVA), iris-IOL distance,
      anterior chamber depth (ACD) and volume (ACV), angle opening distance and
      trabecular-iris space area at 500 and 750 MUm. RESULTS: A Rayner Sulcoflex IOL
      was implanted in seven patients (nine eyes) with negative dysphotopsias. Symptoms
      resolved completely in six eyes, partially in one eye and remained unchanged in
      two eyes. We did not find any significant changes in CDVA. Angle opening
      distance, ACD, ACV and iris-IOL distance reduced significantly after Sulcoflex
      IOL implantation. CONCLUSIONS: Supplementary implantation of a Sulcoflex IOL can
      successfully treat negative dysphotopsia. The decrease in anterior segment
      dimensions in combination with the displacement of light rays by the rounded
      edges of a Sulcoflex IOL may contribute to the resolution of symptoms.

PMID- 25947639
TI  - A novel Cx50 (GJA8) p.H277Y mutation associated with autosomal dominant
      congenital cataract identified with targeted next-generation sequencing.
AB  - BACKGROUND: To unravel the molecular genetic background responsible for autosomal
      dominant congenital pulverulent nuclear cataracts in a four-generation Chinese
      family. METHODS: Family history data were collected, ophthalmological
      examinations were performed, and genomic DNA was extracted from peripheral blood
      of the family members. The candidate genes were captured and sequenced by
      targeted next-generation sequencing, and the results were confirmed by Sanger
      sequencing. The structure modelling of the protein was displayed based on Swiss
      Model Server, and its possible changes in the secondary structure were predicted
      using Antheprot 2000 software. The chemical dissimilarity and possible functional
      impact of an amino acid substitution were performed with Grantham score, PolyPhen
      2, and SIFT predictions. Protein distributions were assessed by confocal
      microscopy. RESULTS: A novel heterozygous c.829C > T transition that led to the
      substitution of a highly conserved histidine by tyrosine at codon 277 (p.H277Y)
      in the coding region of connexin50 (Cx50, GJA8) was identified. Bioinformatics
      analysis showed that the mutation likely altered the secondary structure of the
      protein by replacing the helix of the COOH-terminal portion with a turn. The
      mutation was predicted to be moderately conservative by Grantham score and to be
      deleterious by both PolyPhen-2 and SIFT with consistent results. In addition,
      when expressed in COS1 cells, the mutation led to protein accumulation and caused
      changes in Cx 50 protein localization pattern. CONCLUSIONS: This is a novel
      missense mutation [c.829C > T, (p.H277Y)] identified in exon 2 of Cx50. Our
      findings expand the spectrum of Cx50 mutations that are associated with autosomal
      dominant congenital pulverulent nuclear cataract.

PMID- 25947642
TI  - Biochemical consequences of bariatric surgery for extreme clinical obesity.
AB  - Obesity, defined as a body mass index over 30 kg/m(2) for adults, poses a major
      healthcare challenge with important economic, personal and social consequences.
      Although public health measures, lifestyle change and pharmacological therapies
      have an important role in the management of obesity, patients with established
      morbid obesity (body mass index over 40 kg/m(2)) may also require bariatric
      surgery. Bariatric or metabolic surgery is associated with effective and enduring
      weight loss but is also known to improve glucose homeostasis, blood pressure and
      dyslipidaemia. Patients who have bariatric surgery need lifelong clinical follow
      up to identify and prevent nutritional deficiencies and other complications.
      Clinical biochemistry laboratories have an important role in the nutritional
      assessment of obese patients and in the identification of complications following
      bariatric surgery. The aim of this article is to review the different bariatric
      procedures available and to summarize their complications, especially nutrient
      deficiencies and those of particular relevance to clinical biochemistry
      laboratories. 

PMID- 25947643
TI  - Calibrated automated thrombography for monitoring coagulation function in
      patients with intracerebral haemorrhage.
AB  - OBJECTIVE: To monitor coagulation function in patients with intracerebral
      haemorrhage (ICH) using calibrated automated thrombography. METHODS: Patients
      admitted to hospital with ICH (confirmed within 18 h of symptom onset) were
      enrolled. Patient history and blood samples were obtained within 6 h of
      admission; further blood samples were collected on days 4, 8 and 15 (or on
      discharge between days 9-15: grouped with day 15 data). Blood samples were also
      collected from age- and sex-matched healthy controls. All samples underwent
      calibrated automated thrombography. RESULTS: At admission, thrombin lag time and
      time to peak was longer, and endogenous thrombin potential and peak height were
      lower, in patients with ICH (n = 20) than in healthy controls (n = 29). Lag time
      in patients with ICH gradually decreased, but remained significantly longer than
      in controls until day 8. Time to peak also gradually decreased, but remained
      longer in patients than in controls by day 15. Endogenous thrombin potential and
      peak height gradually increased in patients, but remained lower than in controls
      on day 15. CONCLUSIONS: Patients with ICH have poorer coagulation function than
      healthy individuals, but this function gradually recovers during hospitalization.

PMID- 25947641
TI  - URG4/URGCP enhances the angiogenic capacity of human hepatocellular carcinoma
      cells in vitro via activation of the NF-kappaB signaling pathway.
AB  - BACKGROUND: Angiogenesis is essential for tumor growth. Hepatocellular carcinoma
      (HCC) is characterized by hypervascularity; high levels of angiogenesis are
      associated with poor prognosis and a highly invasive phenotype in HCC. Up
      regulated gene-4 (URG4), also known as upregulator of cell proliferation (URGCP),
      is overexpressed in multiple tumor types and has been suggested to act as an
      oncogene. This study aimed to elucidate the effect of URG4/URGCP on the
      angiogenic capacity of HCC cells in vitro. METHODS: Expression of URG4/URGCP in
      HCC cell lines and normal liver epithelial cell lines was examined by Western
      blotting and quantitative real-time PCR. URG4/URGCP was stably overexpressed or
      transiently knocked down using a shRNA in two HCC cell lines. The human umbilical
      vein endothelial cell (HUVEC) tubule formation and Transwell migration assays and
      chicken chorioallantoic membrane (CAM) assay were used to examine the angiogenic
      capacity of conditioned media from URG4/URGCP-overexpressing and knockdown cells.
      A luciferase reporter assay was used to examine the transcriptional activity of
      nuclear factor kappa - light - chain - enhancer of activated B cells (NF-kappaB).
      NF-kappaB was inhibited by overexpressing degradation-resistant mutant inhibitor
      of kappaB (IkappaB)-alpha. Expression of vascular endothelial growth factor C
      (VEGFC), tumor necrosis factor-alpha (TNFalpha), interleukin (IL)-6, IL-8 and v
      myc avian myelocytomatosis viral oncogene homolog (MYC) were examined by
      quantitative real-time PCR; VEGFC protein expression was analyzed using an ELISA.
      RESULTS: URG4/URGCP protein and mRNA expression were significantly upregulated in
      HCC cell lines. Overexpressing URG4/URGCP enhanced - while silencing URG4/URGCP
      decreased - the capacity of HCC cell conditioned media to induce HUVEC tubule
      formation and migration and neovascularization in the CAM assay. Furthermore,
      overexpressing URG4/URGCP increased - whereas knockdown of URG4/URGCP decreased -
      VEGFC expression, NF-kappaB transcriptional activity, the levels of
      phosphorylated (but not total) IkappaB kinase (IKK) and IkappaB-alpha, and
      expression of TNFalpha, IL-6, IL-8 and MYC in HCC cells. Additionally, inhibition
      of NF-kappaB activity in HCC cells abrogated URG4/URGCP-induced NF-kappaB
      activation and angiogenic capacity. CONCLUSIONS: This study suggests that
      URG4/URGCP plays an important pro-angiogenic role in HCC via a mechanism linked
      to activation of the NF-kappaB pathway; URG4/URGCP may represent a potential
      target for anti-angiogenic therapy in HCC.

PMID- 25947644
TI  - Noninvasive evaluation of renal oxygenation in primary nephrotic syndrome with
      blood oxygen level dependent magnetic resonance imaging: Initial experience.
AB  - OBJECTIVES: To use blood oxygen level dependent (BOLD) magnetic resonance imaging
      (MRI) to evaluate renal oxygenation in patients with primary nephrotic syndrome
      (PNS), and test the hypothesis that renal tissue oxygenation correlates with
      renal function, tubulointerstitial alterations and treatment response. METHODS:
      Patients with untreated first-onset PNS and healthy control subjects underwent
      BOLD MRI. Blood and urine samples were obtained on the day of MRI, and patients
      underwent renal biopsy the day after MRI. Renal tubulointerstitial damage scores
      (TIDS) were determined using Katafuchi criteria. All patients received
      corticosteroids within 7 days after MRI and were followed up for 12 months.
      RESULTS: Medullary R2* values were significantly lower in patients with PNS (n =
      20) than controls (n = 18). Medullary R2* values were negatively correlated with
      estimated glomerular filtration rates and positively correlated with TIDS in
      patients with PNS. There were no significant differences in medullary or cortical
      R2* values when patients were classified according to treatment response.
      CONCLUSIONS: The medullary oxygen concentration was higher in patients with PNS
      than in control subjects. BOLD MRI was a useful noninvasive method for the
      evaluation of renal function and tubulointerstitial impairment.

PMID- 25947646
TI  - VEGF-A levels in bevacizumab-treated breast cancer patients: a systematic review
      and meta-analysis.
AB  - Bevacizumab may improve outcomes of patients with breast cancer, but the absence
      of an established biomarker hampers patient selection and researchers' ability to
      demonstrate a clear survival benefit. Its putative target, circulating VEGF-A,
      emerged as the main candidate and we sought to identify the relationship between
      VEGF-A levels and outcomes through systematic review. We searched electronic
      databases and meeting proceedings for randomized controlled trials (RCTs)
      comparing the addition of bevacizumab to standard chemotherapy for breast cancer.
      RCTs were included if outcomes were presented separately according to VEGF-A
      plasma levels. Random-effects model were applied to calculate the pooled hazard
      ratios for progression-free survival, event-free survival (EFS), comprising
      disease recurrence, progression or any-cause death, and overall survival (OS),
      with respective confidence intervals (95 % CI). High and low VEGF-A levels
      subgroups followed each trial definition, and results were compared using the
      interaction test. Heterogeneity was calculated using chi (2) test (I (2)). Three
      trials enrolled a total of 3748 patients. 1713 patients had baseline VEGF-A
      levels in plasma available for assessment and were included. One trial added
      bevacizumab in the adjuvant setting (N = 2591) and two on first-line metastatic
      disease with taxane-based therapy (N = 1160) There was no interaction between
      VEGF-A levels and study setting (adjuvant vs. first line therapy). Bevacizumab
      improved PFS of patients with above median VEGF-A plasma levels (HR 0.56; 95 % CI
      0.43-0.73; P < 0.001; I (2) = 0 %), but not of those with below median VEGF-A
      levels (HR 0.89; 95 % CI 0.68-1.15; P = 0.37; I (2) = 0 %), with relevant
      differences between these two groups, P-for interaction = 0.02. The same happened
      with EFS (VEGF-A above median HR 0.62; 95 % CI 0.39-0.79; P < 0.001; I (2) = 11
      %; below median HR 0.89; 95 % CI 0.71-1.14; P = 0.98; I (2) = 17 %; P-for
      interaction = 0.03). OS data were not available. VEGF-A level is a reasonable
      candidate biomarker for bevacizumab in the treatment of breast cancer. Further
      studies have to confirm its surrogacy in overall survival and in other scenarios
      including other anti-angiogenic therapies. 

PMID- 25947648
TI  - Viva Questions from the IJDVL.

PMID- 25947649
TI  - Postexercise hypotension after maximal short-term incremental exercise depends on
      exercise modality.
AB  - This study investigated postexercise hypotension (PEH) after maximal
      cardiopulmonary exercise testing (CPET) performed using different exercise
      modalities. Twenty healthy men (aged 23 +/- 3 years) performed 3 maximal CPETs
      (cycling, walking, and running), separated by 72 h in a randomized, counter
      balanced order. Systolic (SBP) and diastolic blood pressure (DBP), heart rate,
      cardiac output, systemic vascular resistance (SVR), autonomic function
      (spontaneous baroreflex sensitivity (BRS) and heart rate variability (HRV)), and
      energy expenditure (EE) were assessed during a 60-min nonexercise control session
      and for 60 min immediately after each CPET. Total exercise volume (EE during CPET
      plus 60 min recovery) was significantly higher in running versus cycling and
      walking CPETs (P <= 0.001). Compared with control, only SBP after running CPET
      was significantly reduced (Delta = -6 +/- 8 mm Hg; P < 0.001). Heart rate and
      cardiac output were significantly increased (P < 0.001) and SVR significantly
      decreased (P < 0.001) postexercise. BRS and HRV decreased after all CPETs (P <
      0.001), whereas sympatho-vagal balance (low- and high-frequency (LF:HF) ratio)
      increased significantly after all exercise conditions, especially after running
      CPET (P < 0.001). Changes in SVR, BRS, sympathetic activity (low-frequency
      component of HRV), and LF:HF ratio were negatively correlated to variations in
      SBP (range -0.69 to -0.91; P < 0.001) and DBP (range -0.58 to -0.93; P <= 0.002).
      These findings suggest that exercise mode or the total exercise volume are major
      determinants of PEH magnitude in healthy men. Because of the running CPET, the
      PEH was primarily related to a decrease in SVR and to an increase in sympatho
      vagal balance, which might be a reflex response to peripheral vasodilatation
      after exercise. 

PMID- 25947650
TI  - The association between medical education accreditation and the examination
      performance of internationally educated physicians seeking certification in the
      United States.
AB  - The purpose of this study was to investigate the performance of graduates of
      international medical schools who seek Educational Commission for Foreign Medical
      Graduates certification based on accreditation of their medical education
      programmes. For the self-selected population who took United States Medical
      Licensing Examinations during the study period (2006-2010), accreditation was
      associated with higher first-attempt pass rates on some examinations, especially
      for international medical graduates from schools located in the Caribbean region.
      In addition, certain essential accreditation standards were associated with
      better performance on all examinations. This study lends support to the value of
      medical education accreditation. 

PMID- 25947651
TI  - Potential benefits of student- and junior doctor-led textbooks.
AB  - INTRODUCTION: Medical textbooks are an important teaching supplement. Few have
      junior doctors or medical students ('juniors') as primary contributors. However,
      the strengths of junior-led face-to-face teaching are now well-established, and
      we hypothesized that similar advantages would be transferrable to a textbook
      setting. METHODS: Juniors were approached to contribute to an independently
      published medical textbook, with senior clinicians recruited in parallel to
      ensure factual accuracy. Juniors directed every aspect of textbook writing and
      the production process. The published book stressed that it was an open
      collaboration with readers, inviting them to get in touch to evaluate the text
      and suggest ideas for new titles. RESULTS: Of 75 respondents, 93 % awarded the
      first textbook in the series 4 or 5 out of 5 for overall quality. Five other
      titles have been released, with seven more in development. Over 100 juniors are
      currently involved, with two students progressing from reviewers to editors after
      less than a year of mentorship. CONCLUSION: Juniors can be a motivated, dynamic,
      innovative group, capable of significant contributions to the medical textbook
      literature. This initiative has generated a sustainable infrastructure to
      facilitate junior-led publishing, and has the capacity for expansion to
      accommodate new initiatives and ideas.

PMID- 25947652
TI  - Eye opener: exploring complexity using rich pictures.
AB  - Historically, approaches to exploring complexity have mainly focused on the
      notion that complex problems must be deconstructed into simpler parts if we are
      to make sense of them; this is the so-called reductionist approach. When dealing
      with the complexity of human experience, however, deconstructing the experience
      without diminishing it is a daunting, perhaps impossible task. Researchers
      wishing to make sense of complex experiences often begin by interviewing the
      individuals at the centre of those experiences. But interviews can be
      frustratingly limited. Visual methods, such as drawings, are beginning to show
      promise for designing research that taps into the complexity of professional
      practice. The promise of visual methods may relate to a key notion in complexity
      research: 'disruptions'. In this paper I introduce the notion of 'disruptions' as
      articulated by complexity approaches from 'systems engineering' and suggest 'rich
      pictures' as an effective visual method to describe and understand complex
      problems in medical education research. 

PMID- 25947653
TI  - State of the art in cell-cell fusion.
AB  - Mammalian life begins with a cell-cell fusion event, i.e. the fusion of the
      spermatozoid with the oocyte and needs further cell-cell fusion processes for the
      development, growth, and maintenance of tissues and organs over the whole life
      span. Furthermore, cellular fusion plays a role in infection, cancer, and stem
      cell-dependent regeneration as well as including an expanded meaning of partial
      cellular fusion, nanotube formation, and microparticle-cell fusion. The cellular
      fusion process is highly regulated by proteins which carry the information to
      organize and regulate membranes allowing the merge of two separate lipid bilayers
      into one. The regulation of this genetically and epigenetically controlled
      process is achieved by different kinds of signals leading to communication of
      fusing cells. The local cellular and extracellular environment additionally
      initiates specific cell signaling necessary for the induction of the cell-cell
      fusion process. Common motifs exist in distinct cell-cell fusion processes and
      their regulation. However, there is specific regulation of different cell-cell
      fusion processes, e.g. myoblast, placental, osteoclast, and stem cell fusion.
      Hence, specialized fusion events vary between cell types and species. Molecular
      mechanisms remain largely unknown, especially limited knowledge is present for
      cancer and stem cell fusion mechanisms and regulation. More research is necessary
      for the understanding of cellular fusion processes which can lead to development
      of new therapeutic strategies grounding on cellular fusion regulation. 

PMID- 25947654
TI  - Fusion in cancer: an explanatory model for aneuploidy, metastasis formation, and
      drug resistance.
AB  - Aneuploidy, metastasis formation, and drug resistance are major issues to
      overcome in most cancers. If there exists common underlying proceedings for the
      formation of these phenomena is still unknown. The searching and thereby better
      understanding of causal mechanisms could promote the generation of drugs
      targeting the ultimate cause of these cancer promoting events. The merging of a
      cancer cell with another cancer cell or normal cell could be one explanation how
      cancer cells could gain advantageous properties and escape eliminating cell fates
      thereby foster cancer progression. This chapter summarizes how cell-cell fusion
      could directly be involved in the pathogenesis of cancer and which often cancer
      associated mechanisms, like viral infections or chronic inflammation, are
      hitherto proposed to trigger cell fusion in cancer context. 

PMID- 25947655
TI  - Mouse embryos' fusion for the tetraploid complementation assay.
AB  - Production of the germline-competent chimeras using genetically modified ES cell
      lines is an essential step in the establishment of novel mouse models. In
      addition chimeras provide a powerful tool to study the cell lineage and to
      analyze complex phenotypes of mutant mice. Mouse chimeras with tetraploid embryos
      are used to rescue extraembryonic defects, to analyze an impact of gene function
      on specific lineage, to study the interaction between embryonic and
      extraembryonic tissues, and to produce mutant embryos and mice for the phenotype
      analysis. Tetraploid embryos are generated by the fusion of two blastomeres of
      the mouse embryo. The applications of tetraploid complementation assay and the
      protocol are described below. 

PMID- 25947656
TI  - Generation of mouse chimeras with high contribution of tetraploid embryonic stem
      cells and embryonic stem cell-fibroblast hybrid cells.
AB  - The in vitro long-term cultivation of embryonic stem (ES) cells derived from pre
      implantation embryos offers the unique possibility of combining ES cells with pre
      implantation embryos to generate chimeras, thus facilitating the creation of a
      bridge between in vitro and in vivo investigations. Genomic manipulation using ES
      cells and homologous recombination is one of the most outstanding scientific
      achievements, resulting in the generation of animals with desirable genome
      modifications. As such, the generation of ES cells with different ploidy via cell
      fusion also deserves much attention because this approach allows for the
      production of chimeras that contain somatic cells with various ploidy. Therefore,
      this is a powerful tool that can be used to study the role of polyploidy in the
      normal development of mammals. 

PMID- 25947657
TI  - Microfluidic systems for cell pairing and fusion.
AB  - Cell fusion has become a routine laboratory technique for generating hybrids with
      diverse genetic and epigenetic properties, and has been used for many different
      applications. Here, we describe a microfluidics based cell pairing and fusion
      method that affords controllable formation of cell pairs and high efficiency
      fusion. The microfluidic device uses passive hydrodynamics and multistep cell
      loading procedure to immobilize and pair thousands of cells in a dense array of
      weir-based traps. Once paired, cells can be fused either using chemical or
      electrical fusion protocols, and provide twofold to tenfold improvement in fusion
      yields in comparison to commercial systems. The hybrids can be harvested from the
      device for culture and further studies. 

PMID- 25947658
TI  - Chromosome tracking in fused cells by single nucleotide polymorphisms.
AB  - Single nucleotide polymorphisms (SNP) refer to single-base differences in DNA
      sequence between individuals of the same species. In experimental setting, inbred
      mouse strains can easily be distinguished by their typical SNPs. Therefore, if
      cell fusion partners are selected to originate from two different genotypes the
      detection of strain specific SNPs in the genome of fused cells can be utilized as
      a complimentary method to traditional karyotyping and cell ploidy analyses to
      monitor the success of the cell fusion procedure and identification of
      chromosomes from both genotypes in established fusion cell lines. In this
      chapter, we describe the method for selection and detection of SNPs on each of
      the 23 pairs of murine chromosome in cell hybrids generated by fusion of murine
      somatic cells originating from DBA/2J female mice and murine embryonic stem (ES)
      cells originating from 129/Ola male mice. While parental fusing partners show the
      presence of only a single strain specific allele the tetraploid fusion hybrid
      cells harbor alleles originating from both fusing partners indicating that the
      fusion clones retained both parental nuclei and at least one of each pair of
      parental autosomes, which were not lost in the course of cell expansion. 

PMID- 25947659
TI  - Fusion of mesenchymal stem cells and islet cells for cell therapy.
AB  - Auxiliary use of mesenchymal stem/stromal cells (MSCs) to islet transplantation
      is shown to enhance efficacy. We hypothesized cell fusion of islet cells and MSCs
      may provide a new cell source with robustness of MSCs and islet cell function. We
      succeeded electrofusion between dispersed islet cells and MSCs in rats and fused
      cells sustained beta-cell function in vitro and in vivo, suggesting their
      possibility of therapeutic application. Here, we describe our method of cell
      fusion that enabled us to fuse islet cells to MSCs. 

PMID- 25947660
TI  - Detection of fusion events in Mammalian skeletal muscle.
AB  - Cell fusion events are essential for the maintenance of skeletal muscle tissue
      and during its repair processes after damage. However, these mechanisms have not
      come much into focus in the recent years. Different methods can be used to assess
      ongoing cell fusion events in adult skeletal muscle tissue. Among these methods,
      confocal microscopy, western blotting, and quantitative polymerase chain
      reactions are ideal, since they provide concerted information about cell fusion
      events going on in skeletal muscle tissue at both qualitative and quantitative
      levels. Confocal microscopy allows for the visualization of exact localizations
      of cell fusion events in adult skeletal muscle. Western blotting allows for a
      semiquantitative evaluation of protein levels involved and associated with cell
      fusions events. Finally, quantitative polymerase chain reaction is a valuable
      tool to precisely assess mRNA levels of genes involved and associated with cell
      fusions events. In addition to the investigation if cell fusion markers in
      skeletal muscle tissue, in vitro cell culture systems (e.g., C2C12 cells) can be
      used to study cell fusions events in a highly standardized system in order to
      obtain detailed information about genes and proteins involved in these processes.
      Here, confocal microscopy, western blotting, and quantitative polymerase chain
      reaction are described as methods to investigate cell fusion events and how a
      C2C12 cell culture system can be run to support the studies of adult muscle
      tissue. 

PMID- 25947661
TI  - FISH Detection of X and Y Chromosomes in Combination with Immunofluorescence to
      Study Contribution of Transplanted Cells to Skeletal Muscle Fibers.
AB  - During the past decades, several studies in animals have displayed the ability of
      cells from the bone marrow (BM) to participate in regeneration of various tissues
      including skeletal muscle tissue. Studies in mice have demonstrated that regular
      physical activity is sufficient to induce contribution of BM derived cells to the
      skeletal muscle tissue, suggesting that this is part of the physiological
      remodeling of skeletal muscle. To analyze whether BM-derived cells participate in
      skeletal muscle remodeling in human, we developed a protocol of
      immunofluorescence in combination with fluorescence in situ hybridization (FISH)
      that enables the detection of male donor bone marrow cell contribution to female
      skeletal muscle tissue. 

PMID- 25947662
TI  - Using phosphatidylserine exposure on apoptotic cells to stimulate myoblast
      fusion.
AB  - The fusion of myoblasts, the skeletal muscle progenitors, is critical for
      skeletal muscle formation, function, and repair after muscle injury. Recognition
      of the phospholipid phosphatidylserine (PtdSer) exposed on certain myoblasts is
      required during fusion into multinuclear myofibers. Cell surface exposure of
      PtdSer is also a feature of cells dying through the process of apoptosis. Here,
      we describe the use of PtdSer exposing apoptotic cells as stimulators of myoblast
      fusion. 

PMID- 25947663
TI  - Tracing myoblast fusion in Drosophila embryos by fluorescent actin probes.
AB  - Myoblast fusion in the Drosophila embryo is a highly elaborate process that is
      initiated by Founder Cells and Fusion-Competent Myoblasts (FCMs). It occurs
      through an asymmetric event in which actin foci assemble in the FCMs at points of
      cell-cell contact and direct the formation of membrane protrusions that drive
      fusion. Herein, we describe the approach that we have used to image in living
      embryos the highly dynamic actin foci and actin-rich projections that precede
      myoblast fusion. We discuss resources currently available for imaging actin and
      myogenesis, and our experience with these resources if available. This technical
      report is not intended to be comprehensive on providing instruction on standard
      microscopy practices or software utilization. However, we discuss microscope
      parameters that we have used in data collection, and our experience with image
      processing tools in data analysis. 

PMID- 25947664
TI  - Analyzing cell fusion events within the central nervous system using bone marrow
      chimerism.
AB  - It has emerged that cells which typically reside in the bone marrow have the
      capacity to cross the blood brain barrier and contribute genetic material to a
      range of neuronal cell types within the central nervous system. One such
      mechanism to account for this phenomenon is cellular fusion, occurring between
      migrating bone marrow-derived stem cells and neuronal cells in-situ.
      Biologically, the significance as to why cells from distinct lineages fuse with
      cells of the central nervous system is, as yet, unclear. Growing evidence however
      suggests that these cell fusion events could provide an efficient means of
      rescuing the highly complex and differentiated neuronal cell types that cannot be
      replaced in adulthood. To facilitate further understanding of cell fusion within
      the central nervous system, we describe here a technique to establish chimeric
      mice that are stably reconstituted with green fluorescent protein expressing sex
      mismatched bone marrow. These chimeric mice are known to represent an excellent
      model for studying bone marrow cell migration and infiltration throughout the
      body, while in parallel, as will be described here, also provide a means to
      neatly analyze both bone marrow-derived cell fusion and trans-differentiation
      events within the central nervous system. 

PMID- 25947665
TI  - Cell fusion between dendritic cells and whole tumor cells.
AB  - We have developed cell fusion vaccines generated with dendritic cells (DCs) and
      whole tumor cells to induce antigen-specific antitumor immunity. This approach
      allows DCs to be exposed to the entire repertoire of tumor-associated antigens
      (TAAs) originally expressed by the tumor cell, to process them endogenously, and
      to present antigenic epitopes thought the MHC class I and class II pathways to
      activate both CD8+ and CD4+ T cells, respectively. The therapeutic efficacy of
      DC/tumor fusion cell vaccines requires the improved immunogenicity of both cells.
      Here, we describe the strategy to generate DC/tumor fusion cells. 

PMID- 25947666
TI  - Membrane nanotube formation in osteoclastogenesis.
AB  - Membrane tunneling nanotubes (TNTs) are unique intercellular structures, which
      enable rapid transport of various materials and rapid communication between cells
      present in a long distance. During osteoclastogenesis, mononuclear osteoclast
      precursors form abundant TNTs in prior to cell-cell fusion. Here we introduce a
      protocol for detecting TNTs during osteoclastogenesis by use of live cell imaging
      utilizing a confocal laser microscopy. We also demonstrate a standard protocol
      for observation of TNTs by scanning electron microscope. 

PMID- 25947667
TI  - Modified Adherence Method (MAM) for Electrofusion of Anchorage-Dependent Cells.
AB  - The artificially induced cell fusion is a useful experimental tool in biology,
      biotechnology and medicine. The electrofusion is a physical method for cell
      fusion that applies high-voltage electric pulses. The use of electric pulses
      causes cell membrane structural changes which bring the cell membrane in the so
      called fusogenic state. When such fusogenic membranes are in close contact cell
      fusion takes place. Physical contact between fusion partners can be achieved by
      various methods and one of them is modified adherence method (MAM) described in
      detail here on B16-F1 cell line. The method is based on the fact that living
      cells form contacts in confluent culture. However, instead of using confluent
      cell culture, in modified adherence method cells are plated in suitable
      concentration and allowed to form contacts for only short predetermined period of
      time. During that time the cells are only slightly attached to the dish surface
      maintaining the spherical shape. Observed high fusion yields up to 50 % obtained
      by MAM in situ by dual-color fluorescence microscopy are among the highest in
      field of electrofusion. The method can be readily adapted to other anchorage
      dependent cell lines. 

PMID- 25947668
TI  - FRET in the Analysis of In Vitro Cell-Cell Fusion by Flow Cytometry.
AB  - Cell-cell fusion is a frequent event in nature leading to modification of cell
      fate. In this chapter, we describe a flow cytometric procedure for the
      quantitative assessment of in vitro cell-cell fusion events that allows the
      discrimination of fused from aggregated cells. The assay is based on the
      differential labeling of fusion partners with lipophilic fluorescent probes DiI
      (red) and DiO (green). Double fluorescent fused cells can be detected after
      coculturing by means of a flow cytometer equipped with a 488 nm laser. Fusion
      events can be distinguished from cell aggregates by the enhancement of the DiI
      red fluorescence intensity due to resonance energy transfer between the two
      probes occurring in the fused but not in the aggregated cell population. 

PMID- 25947669
TI  - Dual Split Protein (DSP) Assay to Monitor Cell-Cell Membrane Fusion.
AB  - Fusion between viral and cellular membranes is the essential first step in
      infection of enveloped viruses. This step is mediated by viral envelope
      glycoproteins (Env) that recognize cellular receptors. The membrane fusion
      between the effector cells expressing viral Env and the target cells expressing
      its receptors can be monitored by several methods. We have recently developed a
      pair of chimeric reporter protein composed of split Renilla luciferase (RL) and
      split GFP. We named this reporter dual split protein (DSP), since it recovers
      both RL and GFP activities upon self reassociation. By using DSP, pore formation
      and content mixing between the effector and target cells can be monitored upon
      the recovery of RL and GFP activities after the membrane fusion. This quick assay
      provides quantitative as well as spatial information about membrane fusion
      mediated by viral Env. 

PMID- 25947670
TI  - Photoconvertible fluorescent protein-based live imaging of mitochondrial fusion.
AB  - Mitochondria are highly dynamic organelles that undergo fusion and fission on a
      relatively fast time scale. Here, a straightforward method is described for
      capturing mitochondrial fusion events in real time using a photoconvertible
      fluorescent protein and a far-field fluorescence microscope equipped with
      appropriate image acquisition and analysis software. The Kaede photoconvertible
      fluorescent protein is tagged with a mitochondrial targeting sequence and
      delivered to primary neurons by lentiviral transduction, which ensures efficient
      low copy number transgene insertion, as well as stable transgene expression. 

PMID- 25947671
TI  - The role of ambient ice-like water adlayers formed at the interfaces of graphene
      on hydrophobic and hydrophilic substrates probed using scanning probe microscopy.
AB  - In this work, we report the role of ice-like water adlayers (IWLs) formed under
      ambient conditions in between mechanically exfoliated as-prepared and patterned
      few layer graphene (FLG) and multi-layer graphene (MLG) on hydrophobic Si and
      hydrophilic SiO2/Si substrates. The growth of the IWL is probed by measuring the
      height changes in graphene using intermittent contact atomic force microscopy (IC
      AFM) and their electrostatic effect is studied using electrostatic force
      microscopy (EFM) over time. It is found that more IWLs are formed within a
      shorter period of time, when both as-prepared graphene and underlying substrates
      are either hydrophobic or hydrophilic in nature. In contrast, AFM voltage
      nanolithographically patterned trenches on FLG and MLG on the Si substrate show
      quick formation of IWLs. The effect of IWL formed, on the dimensions of trenches,
      is correlated with the variation of the measured EFM phase shift over time. This
      study demonstrates the dependence of the formation of IWLs under ambient
      conditions on the affinity towards water, at the interface of graphene on
      hydrophobic and hydrophilic substrates, which has important implications for the
      performance of graphene-based nanoelectronic devices. 

PMID- 25947672
TI  - Studies in Australian Katydids: A Review of the Australian Snub-nosed Sylvan
      katydids (Tettigoniidae; Pseudophyllinae; Simoderini).
AB  - The Australian members of the simoderine katydids are reviewed. The tribe is
      known from nine genera, five of which occur only in Madagascar, the others are
      Australian: Chloracantha Hebard (C. lampra, C. angularis sp. nov., C. garradunga
      sp. nov., C. hilleri sp. nov.), Tallebudgeroptera gen. nov. (T. spininota sp.
      nov.), Mastigaphoides Weidner (M. haffneri, M. tuberculatus sp. nov., M.
      vaginalis sp. nov., M. lewisensis sp. nov.), Narea Walker (N. compacta, N.
      elongata, N. kungaree sp. nov.). Mastighapha Karsch is synonymised with Narea.
      Descriptions, illustrations, sound recording information and distribution maps
      are presented for all species. 

PMID- 25947673
TI  - Sexual dimorphism in Autogneta, with description of three new species from North
      America and new diagnosis of the genus (Acari, Oribatida, Autognetidae).
AB  - Species in the oribatid mite genus Autogneta are primarily Palaearctic, with a
      few, mainly unidentified records from North America. Strong sexual dimorphism is
      reported in the genus for the first time; it is expressed by a posterior porose
      region on the male notogaster that in some species is associated with
      modifications of notogastral setae h<sub>1 </sub>and p<sub>1</sub>. Herein, I
      describe 3 new dimorphic Autogneta species from North America, based on adult
      specimens: A. aokii sp. nov. and A. schusteri sp. nov., from California, USA, and
      A. flaheyi sp. nov., from British Columbia and Alberta, Canada. New diagnoses for
      2 other dimorphic species, the type species Autogneta longilamellata (Michael)
      and A. amnica Jacot, are presented that accommodate their previously unreported
      dimorphic males. Autogneta flumengalei Jacot is recombined as Conchogneta
      flumengalei (Jacot) comb. nov. Finally, I give a key to adults of Autogneta
      species known from North America. 

PMID- 25947674
TI  - Two new species of Amazophrynella (Amphibia: Anura: Bufonidae) from Loreto, Peru.
AB  - Amazophrynella is a taxonomically poorly known bufonid genus with a pan-Amazonian
      distribution. A large part of this ambiguity comes from taxonomic uncertainties
      regarding the type species A. minuta. In this study we compare morphological and
      molecular data of topotypic specimens of A. minuta with all other nomical
      congeneric species. Based on these comparisons, we describe two new species. The
      first species, A. amazonicola sp. nov., differs from other recognized congeners
      by having a tip of snout with a small triangular protrusion (in dorsal and
      lateral view), spiculated body and basal webbing on fingers I and II. The second
      species, A. matses sp. nov., differs from congeners by the smallest snout to vent
      length of the genus, edges of nasal protrusion dilated and elliptical shape
      palmar tubercles. The two species are allopatric, where the first species is
      known to be associated with white sand forests (=campinaranas), while the second
      inhabits upland (=terra firme) forests. Both species are diagnosable by a series
      of substitutions in the 16S rDNA, and both species are highly divergent from
      their sister taxa (p-distances range from 7-14%). 

PMID- 25947675
TI  - A new species of Troglocharinus Reitter, 1908 (Coleoptera, Leiodidae, Cholevinae,
      Leptodirini) from southern Catalonia, with a molecular phylogeny of the related
      species group.
AB  - In this paper we describe T. pallisei sp. n., a new representative of the genus
      Troglocharinus Reitter, 1908 (Coleoptera, Leiodidae, Leptodirini), a strictly
      subterranean genus restricted to the Eastern Pyrenees and some coastal areas in
      Catalonia. All known specimens of T. pallisei sp. n. were collected in a cave
      next to the town of La Riba, in the province of Tarragona (Spain), situated
      between the distribution areas of the species of the T. orcinus complex and T.
      espanoli Jeannel, 1930. It can be separated from the other members of the T.
      orcinus complex by the presence of penicillus in the apex of the parameres of the
      aedeagus and from T. espanoli by the presence of a mesoventral keel; it also
      differs from both by its long and erect pubescence. A Bayesian molecular
      phylogeny including representatives of the main lineages within the genus
      Troglocharinus, based on ca. 5211 Kb of 5 mitochondrial and 4 nuclear genes,
      placed T. pallisei sp. n. as sister to T. orcinus Jeannel, 1910, and both sister
      to T. espanoli, in perfect agreement with their geographic distributions and the
      inferred geographic expansion of the genus to the south, with an estimated
      divergence of ca. 1.3 Ma. In agreement with the results of a previous
      phylogenetic study, the subgenus Antrocharidius Jeannel, 1910 is synonymised with
      Troglocharinus (syn.n.). 

PMID- 25947676
TI  - Redescription of Libanasa brachyura Karny, 1928. (Orthoptera: Anostostomatidae:
      ?Lutosinae) from Tanzania and problems at the subfamily level.
AB  - Libanasa brachyura Karny, 1928 is resurrected and redescribed. Morphological
      details are added which now question its placement in the Lutosinae, and this in
      turn questions the subfamily arrangements as a whole. New characters are
      introduced for future comparison with other genera. Some details of its biology
      are also added. 

PMID- 25947677
TI  - Ngirhaphium Evenhuis & Grootaert from southern Thailand (Diptera: Dolichopodidae)
      with the description of a new species.
AB  - The genus Ngirhaphium Evenhuis & Grootaert, 2002 is reported for the first time
      from Thailand in particular from mangroves on the coast of the Andaman Sea in
      southern Thailand. Three species were found: N. murphyi Evenhuis & Grootaert,
      2002, N. sivasothii Grootaert & Puniamoorthy, 2014 and N. chutamasae sp. nov. The
      latter species is described and illustrated and a key to all four known species
      is provided. COI barcode data showed that the new species is most closely related
      to N. murphyi with a genetic distance of 7%. The distance with the other species
      is 11 to 12%. 

PMID- 25947678
TI  - Spring-cleaning of African agathidines: new combinations for five species
      previously placed in Cremnops Forster (Hymenoptera: Braconidae).
AB  - Little work has been done with the African species of Cremnops since their
      original descriptions. Herein we propose new combinations for five species that
      are currently placed in Cremnops, i.e., C. atripennis Szepligeti 1914 and C.
      elegantissima Szepligeti 1908 are moved to Disophrys; C. borealis (Szepligeti
      1914) and C. rubrigaster Masi 1944 are moved to Biroia; and C. pulchripennis
      Szepligeti 1905 is moved to and renamed Biroia neopulchipennis. These changes
      result in Disophrys atripennis (Szepligeti 1915) becoming a jr. homonym, which we
      change to Disophrys szatripennis. Additionally, two species are proposed as nomen
      dubia: C. rufitarsis Szepligeti 1913 and C. schubotzi Szepligeti 1915. 

PMID- 25947680
TI  - Ateuchus cujuchi n. sp., a new inquiline species of Scarabaeinae (Coleoptera:
      Scarabaeidae) from tuco-tuco burrows in Bolivia.
AB  - In 2012, P. Skelley and J. Wappes were investigating the insect fauna of Ctenomys
      (Blainville, 1826) (Rodentia: Ctenomyidae) burrows at low elevation in Santa Cruz
      de la Sierra province, Bolivia. A number of beetles were extracted from this
      microhabitat and among them, 50 specimens belonging to the New World genus
      Ateuchus Weber from the subfamily Scarabaeinae (Coleoptera: Scarabaeidae). The
      specimens were submitted to the author for identification and did not match any
      currently described species. Although South American species of the genus
      Ateuchus are critically in need of a modern revision, it is considered important
      to describe this particular species as it is the first one recorded from mammal
      burrows in South America and it is easily distinguishable from all other known
      Ateuchus. 

PMID- 25947679
TI  - Description of the male of Dolomedes raptoroides Zhang, Zhu & Song, 2004
      (Araneae: Lycosoidea: Pisauridae).
AB  - Dolomedes Latreille, 1804 is the most diverse genus in Pisauridae, with 98
      described species and a wide range of distribution on every continent, except
      Antarctica (World Spider Catalog 2014). The genus has never been comprehensively
      revised. Roewer's (1955) monograph covered African species of the genus; Carico
      (1973) revised the Nearctic species; Vink & Duperre 2010 revised the four
      Dolomedes species of New Zealand. 

PMID- 25947681
TI  - New substitute name for the genus Napo Shaw, 2012 (Hymenoptera: Braconidae:
      Euphorinae).
AB  - The braconid genus Napo was established by Shaw (2012) for a single species Napo
      townsendi Shaw, 2012 from Napo Province, Ecuador. However, the genus name Napo is
      preoccupied and was initially introduced by Linnavuori & DeLong (1976) for a
      deltocephalinae leafhopper genus with Napo brazosellus Linnavuori & DeLong, 1976
      as the type species (Hemiptera: Cicadellidae). Thus, the genus Napo Shaw, 2012 is
      a junior homonym of the genus Napo Linnavuori & DeLong, 1976. According to
      Article 60 of the ICZN (2015), we propose the new replacement name Yanayacu nom.
      nov. for Napo Shaw, 2012. The resulting nomenclatural changes are summarized
      below. 

PMID- 25947682
TI  - Monochoroterpes, a replacement name for Monophyllus Kluge, 2012 (Insecta:
      Ephemeroptera), nec Monophyllus Leach, 1821 (Mammalia: Chiroptera).
AB  - The genus group name Monophyllus Kluge, 2012 was established to include a single
      species of the mayfly family Leptophlebiidae (Insecta: Ephemeroptera) from Hainan
      Island, China, Choroterpes (Monophyllus) monophyllus Kluge, 2012. Unfortunately,
      this name is preoccupied by Monophyllus Leach, 1821, a genus of Phyllostomidae
      bats (Mammalia: Chiroptera) from the Antilles (type species: M. redmani Leach,
      1821: 76). Therefore, we propose a replacement name for the mayfly genus group as
      follows. 

PMID- 25947683
TI  - A new tribe and species of Clastopterinae (Hemiptera: Cercopoidea:
      Clastopteridae) from Africa, Asia and North America.
AB  - Additional evidence supports the inclusion by Hamilton (2001) of Machaerotinae in
      Clastopteridae. The former Clastopteridae (Clastopterinae sensu Hamilton, 2001)
      is revised to include Sepulliini (tr. nov.) Clastopterini includes a fossil genus
      Prisciba Poinar & Brown and the extant Clastoptera with 2 new species both from
      North America, and Iba Schmidt from the old-world. The last of these has 3
      species (1 new), 2 from the Philippines and 1 in subgenus Parahindoloides
      Lallemand, stat. nov., from Borneo. Sepulliini includes 5 genera and 52 species
      from Africa, India and southeast Asia that were formerly included in
      "Aphrophoridae" but are now transferred to the redefined subfamily
      Clastopterinae, linking Clastopterini to Zygonini of the subfamily Machaerotinae.
      Sepulliini includes 24 newly described species: 2 species of Beesoniella
      Lallemand from India, and 1 of Grellaphia Schmidt from the Philippine Islands;
      and from continental Africa 2 species of Sepullia Stal from Ethiopia and Angola,
      Taphrotylus insignificans gen. & sp. nov. from Madagascar and 18 new species of
      Tremapterus Spinola, making Tremapterus (including Abbalomba Distant, Nyanja
      Distant and Patriziana Lallemand as subgenera) the largest and most widespread
      genus in Sepulliini. Its 38 species in sub-Saharan Africa include 2 new
      subgenera: Selenion (1 species) and Tremiziana (4 species). In this study, 25 new
      combinations are created: 20 in Tremapterus with T. major Jacobi (1910),
      described from Mt. Kilimandjaro, and T. occidentalis Schumacher (1912), described
      from above 1800 m on Mt. Cameroon transferred to Witteella Lallemand (Cercopidae,
      Aphrophorinae); Penthimia maculipennis Spinola and Philaenus maculosa Walker are
      transferred to Clastoptera Germar, and Parahindoloides lumuana Lallemand to Iba.
      The many new species and new combinations in the old-world fauna of
      Clastopterinae are included in keys and a checklist. 

PMID- 25947684
TI  - A review of the genus Xiphovelia Lundblad, 1933 (Hemiptera: Heteroptera:
      Veliidae) from China, with descriptions of three new species.
AB  - Four species of genus Xiphovelia Lundblad are now known from China. Of these, X.
      glauca Esaki & Miyamoto, 1959 is the only member of the genus previously recorded
      from China. In addition, three species, X. denigrata sp. nov., X. fulva sp. nov.
      and X. reflexa sp. nov., are described as new to science. Photographs of the male
      and female dorsal habitus, male fore and middle legs, male abdominal segment VIII
      and endosoma with pygophore are provided, accompanied by habitat photographs and
      a distribution map for all Chinese Xiphovelia species. A key to all the four
      Chinese Xiphovelia species is also provided. 

PMID- 25947685
TI  - A likely microendemic new species of terrestrial iguana, genus Chalarodon, from
      Madagascar.
AB  - A new species of the hitherto monotypic genus Chalarodon is described from
      southern Madagascar and a lectotype (ZMB 4360) is designated for C.
      madagascariensis Peters, 1854. The new species of terrestrial iguana, Chalarodon
      steinkampi sp. nov., is defined by several morphological characters and by
      concordant differentiation in mitochondrial and nuclear DNA with >5% uncorrected
      pairwise genetic distance in the 16S rRNA gene. It can be most clearly recognized
      by the presence of smooth (vs. keeled) gular and ventral scales, a spotted
      pattern extending from flanks onto belly, and an unpigmented throat. The new
      species is known from only a small area between the villages of Amboasary Sud and
      Esomony, located west of the Andohahela Massif, while C. madagascariensis appears
      to be widespread over much of southern and western Madagascar. We highlight the
      need for further exploration of this unprotected region which might host several
      other microendemic species. 

PMID- 25947686
TI  - Description of three new species of Pentelicus Howard (Hymenoptera: Encyrtidae)
      from India, with a key to world species.
AB  - Three new species of Pentelicus Howard (Hymenoptera: Encyrtidae) are described
      from Tamil Nadu, India: P. funiculatus sp. nov., P. punctatus sp. nov. and P.
      depunctatus sp. nov. A revised key to the world species of Pentelicus is also
      provided. 

PMID- 25947687
TI  - Three new species of Diaphorus Meigen (Diptera: Dolichopodidae) from Tibet.
AB  - The species of Diaphorus Meigen from Tibet are reviewed. Previously only one
      species, Diaphorus xizangensis Yang & Grootaert, was known to occur in Tibet. The
      following three species are described as new to science: Diaphorus baheensis sp.
      nov., Diaphorus longrenensis sp. nov. and Diaphorus nigripedus sp. nov. Diaphorus
      anatoli Negrobov is recorded from Tibet for the first time. A key to the species
      of Diaphorus from Tibet and the Himalayan area is presented. 

PMID- 25947688
TI  - Two new species of the genus Igerna (Hemiptera: Cicadellidae: Megophthalminae)
      from India.
AB  - Two new megophthalmine species of leafhoppers, Igerna kolasibensis sp. nov. and
      I. shillongensis sp. nov., are described from India, Mizoram and Meghalaya,
      respectively. Detailed morphological descriptions, illustrations and photographs
      are provided. An updated key to the species and taxonomic notes on the genus are
      provided. 

PMID- 25947689
TI  - Revisionary study on European species of the Empria candidata complex
      (Hymenoptera, Symphyta, Tenthredinidae).
AB  - Two species of the Empria candidata species complex, E. candidata (Fallen, 1808)
      and E. magnicornis (Eversmann, 1864) spec. rev., comb. nov., are revised and
      redescribed. The males and larvae of both species are identified, described and
      the males are associated with the corresponding females. The species are
      redefined based on the revision of the available types. Lectotypes are designated
      for Tenthredo (Allantus) repanda Klug, 1816 and Tenthredo (Macrophya) magnicornis
      Eversmann, 1864. 

PMID- 25947690
TI  - A new species, new immature stages, and new synonymy in Australian Dasybasis
      flies (Diptera: Tabanidae: Diachlorini).
AB  - Australian beach sand is a productive habitat for lower brachyceran fly larvae
      but often overlooked by collectors. We collected two species of tabanid larvae
      from coastal beach sand in southern New South Wales in August 2013. Both species
      belong to the Dasybasis macrophthalma species-group of Mackerras (1959), one a
      new species, and the other D. exulans (Erichson, 1842). We describe both new
      immature stages and the new species adult as Dasybasis rieki sp. nov. (Diptera:
      Tabanidae: Diachlorini). Trojan (1994b) elevated the D. macrophthalma species
      group to the genus Sznablius. We review the evidence for the generic status of
      Sznablius, and synonymize it with Dasybasis. 

PMID- 25947691
TI  - New species and records of frog-biting midges from southern Brazil (Diptera:
      Corethrellidae).
AB  - Corethrella borkenti sp. n. is described, based on female and male adults, pupae
      and larvae, collected from tank bromeliads in the Atlantic Forest of southern
      Brazil. The larva and pupa of C. alticola Lane, 1939 are described for the first
      time. New distributional records for C. alticola and C. vittata Lane, 1939 extend
      their distributions to the southern Atlantic Forest. A key to pupae of peruviana
      group is given. 

PMID- 25947692
TI  - A new genus of Iassinae (Hemiptera: Cicadellidae) from Peru and a new species of
      Daveyoungana Blocker & Webb.
AB  - The new iassine leafhopper genus Linnavuoria is described and illustrated based
      on L. tingomariaensis sp. nov., from Peru, and placed in the previously monobasic
      tribe Selenomorphini (based on Selenomorphus Evans from New Caledonia), along
      with two other New World genera, Pachyopsis Uhler and Scaroidana Osborn (new
      placements). The new genus is similar to Pachyopsis in overall structure, but
      differs as follows: head with crown flat and forming distinct angle with face in
      profile; face coarsely punctate, without distinct transverse striations or rugae;
      lateral frontal sutures extended from antennal ledge to midline and joining with
      distinct coronal suture; forewing with numerous dark pigment spots corresponding
      to setal sockets; hind femur with macrosetal formula 2+1+1+1. A revised diagnosis
      and key to genera are given for Selenomorphini. The previously monotypic
      leafhopper genus Daveyoungana Blocker & Webb (Iassinae: Hyalojassini) recorded
      from Brazil is also reviewed and the detailed morphology of the genus is
      redescribed and illustrated, including the first description of the female. A new
      species, D. maniforma sp. nov. from Ecuador is described and illustrated and a
      key to the species in this genus is given. 

PMID- 25947693
TI  - The tadpole of Dendropsophus branneri (Cochran, 1948) (Amphibia, Anura, Hylidae).
AB  - Dendropsophus branneri is a small treefrog largely distributed throughout the
      Tropical Atlantic and Caatinga morphoclimatic domains (see Ab'Saber 1977 for
      morphoclimatic domains), from northeastern to southeastern Brazil [Lutz 1973,
      Frost 2014; see Zina et al. 2014 for taxonomic comments on D. minusculus (Rivero,
      1971) and D. branneri]. This species is currently placed in the D. microcephalus
      species group according to Bastos & Pombal (1996) and Faivovich et al. (2005).
      The D. microcephalus group comprises 36 species (Frost 2014), 14 of which have
      known tadpoles. Here, we describe the external morphology and color patterns of
      the previously unknown tadpole of D. branneri. 

PMID- 25947694
TI  - Molecular and morphological assessment of Delma australis Kluge (Squamata:
      Pygopodidae), with a description of a new species from the biodiversity 'hotspot'
      of southwestern Western Australia.
AB  - The Australian pygopodid lizard genus Delma is characterised by morphologically
      conservative but genetically divergent lineages and species. An initial
      assessment of molecular and morphological variation in Delma australis Kluge,
      1974 throughout its main distribution in Western and South Australia reveals at
      least two undescribed species that are presently included under this epithet.
      Here we describe the most distinctive and easily diagnosed taxon of these, D.
      hebesa sp. nov., from the proteaceous scrub and mallee heath on the south coast
      sandplains of southwestern Western Australia. We also foreshadow the need for an
      expanded genetic framework to assist in unequivocally diagnosing additional
      candidate species in D. australis, which is redescribed herein and shown to be
      monophyletic for those specimens sampled, albeit displaying geographic variation
      in a range of molecular and morphological characters. Delma hebesa sp. nov.
      differs from all other described Delma species, including regional populations of
      D. australis, by a combination of molecular genetic markers, colouration and
      scalation. Based on phylogenetic affinities and shared morphologies, a D.
      australis species-group is proposed to accommodate D. australis, D. torquata and
      the new species described herein. The addition of another new vertebrate species
      from southwestern Western Australia, recognised globally as a biodiversity
      'hotspot', underlines our lack of understanding of genetic diversity and
      evolutionary histories in this biodiverse region. 

PMID- 25947695
TI  - The identity of the semiterrestrial crab Terrathelphusa kuchingensis (Nobili,
      1901) (Crustacea: Decapoda: Brachyura: Gecarcinucidae), with descriptions of four
      new species from southwestern Sarawak, Borneo, Malaysia.
AB  - Four new species of semiterrestrial gecarcinucid crabs are described from
      limestone and sandstone habitats in southwestern Sarawak, Malaysia:
      Terrathelphusa aglaia n. sp., T. cerina n. sp., T. kundong n. sp., and T. mas n.
      sp. The taxonomy of T. kuchingensis (Nobili, 1901) is discussed, its precise
      identity ascertained from fresh material, and its actual distribution determined.
      This increases the number of Terrathelphusa species in Borneo to eight. 

PMID- 25947696
TI  - The Tanytarsini (Diptera: Chironomidae) in the collection of the Museum of Amber
      Inclusions, University of Gdansk.
AB  - Non-biting midges of the tribe Tanytarsini collected in the Museum of Amber
      Inclusions, University of Gdansk, Poland, are reviewed. Among over 1500
      chironomid specimens examined (inclusions in Baltic amber), 44 Tanytarsini
      individuals were found, of which 27 well preserved specimens were determined to 7
      species, including 3 species described as new. Stempellinella electra sp. nov.
      (male) displays morphological hypopygial characters unique for the genus, and the
      antenna composed of 13 flagellomeres. A new checklist of fossil and extant
      species of this genus is also given, including Stempellinella sofiae (Fusari et
      Lamas, 2014) comb. nov. Tanytarsus glaesarius sp. nov. (male) is the only Eocene
      species of the genus with a reduced number of antennal flagellomeres. Tanytarsus
      protogregarius sp. nov. (male) is the oldest known representative of the
      gregarius species group. Notes on phylogenetic relations of the new species with
      their extant congeners are also provided. 

PMID- 25947697
TI  - Species of Lissothrips and Williamsiella from mosses and lichens in Australia and
      New Zealand (Thysanoptera, Phlaeothripinae).
AB  - Species of Lissothrips and Williamsiella live in association with mosses and
      lichens. Their gut contents are commonly blue-green, suggesting that they
      possibly feed on blue-green algae. Three species of Lissothrips are known from
      New Zealand, of which two are here recorded from Australia together with six new
      species. Williamsiella is recorded from Australia for the first time, with one
      new species. 

PMID- 25947698
TI  - Saturnia jonasii Butler, 1877 on Jejudo Island, a new saturnid moth of South
      Korea with DNA data and morphology (Lepidoptera: Saturniidae).
AB  - Saturnia (Rinaca) jonasii Butler, 1877 is distributed in Japan, including
      Tsushima Island and Taiwan, whereas S. boisduvalii Eversmann, 1846 is distributed
      in northern areas, such as China, Russia, and South Korea. In the present study
      we found that the specimens from Mt. Hallasan on Jejudo, a southern remote
      offshore island, were S. jonasii, rather than S. boisduvalii based on morphology,
      DNA barcode, and nuclear elongation factor 1 alpha (EF-1alpha) sequences. The
      major morphological differences between the two species included the shape of
      wing pattern elements of fore- and hindwings and male and female genitalia. A DNA
      barcode analysis of the sequences of the Jejudo specimens and S. boisduvalii,
      along with those of Saturnia species obtained from a public database showed a
      minimum sequence divergence of 4.26% (28 bp). A phylogenetic analysis also showed
      clustering of the Jejudo specimens with S. jonasii, separating S. boisduvalii
      (Bayesian posterior probability = 0.99). The EF-1alpha-based sequence and
      phylogenetic analyses of the two species from Jejudo Island and the Korean
      mainland showed the uniqueness of the Jejudo specimens from S. boisduvalii
      collected on the Korean mainland, indicating distribution of S. jonasii on Jejudo
      Island in South Korea, instead of S. boisduvalii. 

PMID- 25947699
TI  - An endemic new species of Ameiva (Squamata: Teiidae) from an isolated dry  
      forest in southern Peru.
AB  - We describe a new species of Ameiva from an interandean dry forest in central
      southern Peru. Ameiva reticulata sp. nov. represents the fifth species in the
      genus known to occur in Peru. The new species is similar to the species of the A.
      ameiva complex such as A. ameiva, A. atrigularis, A. pantherina, and A.
      praesignis, and is distinguished from these by a smaller size, a lower count of
      dorsal scales along the middorsal line and scales across the midbody, and by the
      gular coloration.

PMID- 25947700
TI  - An important new fossil genus of Berothinae (Neuroptera: Berothidae) from Baltic
      amber.
AB  - Elektroberotha groehni gen. et sp. nov. (Neuroptera: Berothidae) is described
      from Baltic amber. The genus is assigned to Berothinae based on female terminalia
      that have the following characteristics: long hypocaudae on gonocoxite 9;
      sternite 7 that is medially divided into a pair of lateral sclerites; and
      gonocoxite 8 with a medial process that is very similar to that of some extant
      berothine genera. The new genus is the first described fossil genus of the
      subfamily Berothinae. It is noteworthy for the possession of a fully-developed
      CuP in the hind wing, a vein that is strongly reduced in all other species of the
      subfamily. The genus Spiroberotha is considered to belong to the Berothinae. 

PMID- 25947701
TI  - Revision of the genus Jezarotes Uchida (Hymenoptera: Ichneumonidae: Acaenitinae),
      with the description of a new species from Laos.
AB  - Two Japanese species of Jezarotes, J. tamanukii Uchida, 1928, and J. yamatonis
      Uchida, 1928, are synonymized based on the results of a morphological examination
      and DNA sequence analysis of the mitochondrial COI gene. Jezarotes tetragonis Lee
      & Lee, 2009, from Korea is also synonymized with J. tamanukii. The key to the
      world's species of Jezarotes proposed by Lee & Lee (2009) is updated, including a
      new species J. mitai sp. nov. from Laos. 

PMID- 25947702
TI  - New species of Medetera (Diptera: Dolichopodidae, Medeterinae) from Tibet.
AB  - Only one species of Medetera Fischer von Waldheim was known to occur previously
      in Tibet. Here the following three species of Medetera are described as new to
      science: Medetera exornata sp. nov., Medetera furva sp. nov. and Medetera sinuosa
      sp. nov. The first two species belong to the apicalis group, and the last one
      belongs to the diadema-veles group. A key to the species of Medetera from the
      Himalayas is provided. 

PMID- 25947703
TI  - Serromyia diabolica, a new biting midge species from Lebanon (Diptera:
      Ceratopogonidae).
AB  - A new darkly-pigmented species of Serromyia, closely related to S. subinermis
      Kieffer, is described from both sexes based on morphological characters and COI
      gene sequence analyses. 

PMID- 25947704
TI  - Description of the second fossil Baltic amber species of Monotomidae (Coleoptera:
      Cucujoidea).
AB  - Based on a specimen from the Upper Eocene Baltic amber (Kaliningrad Region,
      Russia), Aneurops daugpilensis sp. nov. is described. The new species is similar
      to the extant A. convergens (Sharp, 1900) and A. championi Sharp, 1900
      distributed in North and Central America, but differs in the larger punctation of
      pronotum, and shorter and sparser setation of the median plaque on ventrite 1.
      Aneurops daugpilensis sp. nov. is distinguished from Europs insterburgensis
      Alekseev, 2014 by having a median plaque on ventrite 1, a larger body size, and
      distinctly sparser punctation of the forebody. 

PMID- 25947705
TI  - The Sarcophagidae (Insecta: Diptera) described by Chien-ming Chao and Xue-zhong
      Zhang.
AB  - The twenty-nine species-group names of Sarcophagidae proposed by Chien-ming Chao
      and Xue-zhong Zhang are reviewed. Of these names, twenty-four are available,
      while five are unavailable nomina nuda. Of the twenty-four available names, nine
      are considered valid, fifteen as invalid: thirteen junior synonyms, one
      unnecessary replacement name and one junior primary homonym. Holotypes of all
      species, and allotypes when available, are photographed and the species
      redescribed based on the type material. Eight new synonyms are proposed:
      Miltogramma tibita Chao & Zhang, 1988, syn. n. of Miltogramma taeniata Meigen,
      1824; Sphenometopa luridimacula Chao & Zhang, 1988, syn. n. of Sphenometopa
      stackelbergiana Rohdendorf, 1967; Sphenometopa mesomelaenae Chao & Zhang, 1988,
      syn. n. of Sphenometopa stelviana (Brauer & Bergenstamm, 1891); Sphenometopa
      altajica Rohdendorf, 1971, syn. n. of Sphenometopa stelviana (Brauer &
      Bergenstamm, 1891); Sarcophila mongolica Chao & Zhang, 1988, syn. n. of
      Sarcophila latifrons (Fallen, 1817); Wohlfahrtia brevicornis Chao & Zhang, 1996,
      syn. n. of Wohlfahrtia grunini Rohdendorf, 1969; Wohlfahrtia hirtiparafacialis
      Chao & Zhang, 1996, syn. n. of Wohlfahrtia magnifica (Schiner, 1862); and
      Wohlfahrtiodes mongolicus Chao & Zhang, 1988, syn. n. of Asiosarcophila kaszabi
      Rohdendorf & Verves, 1978. The genus Asiosarcophila Rohdendorf & Verves, 1978 is
      herewith reported from China for the first time, along with the five species A.
      kaszabi, M. taeniata, S. stackelbergiana, S. stelviana and W. grunini. 

PMID- 25947706
TI  - A new genus and species of delphacid planthopper (Hemiptera: Fulgoroidea:
      Delphacidae) from Central America with a preliminary regional species list.
AB  - The new genus Ampliphax, assigned to the Delphacini, is described and illustrated
      with a single new species A. grandis from Costa Rica and Panama. Ampliphax
      grandis is a large species with a projected head. DNA barcode data suggest, among
      currently barcoded taxa, an affinity to the genus Bostaera. A checklist of the
      delphacid species from Costa Rica, Panama, and Nicaragua based on literature and
      specimen records is provided. 

PMID- 25947707
TI  - New species of Cymatodera Gray (Coleoptera: Cleridae: Tillinae) from Mexico and
      Central America, with notes on others.
AB  - Nineteen new species of Cymatodera Gray are described: C. mexicana, C.
      cicatricula, C. matehualacaligoides, C. brailovskyi, C. durangoensis, C.
      monticola, C. paucipunctata, C. anulata, C. christina, C. copei, C. oxchuc, C.
      merickeli, C. romeroi, C. cellulosa, and C. acutipennis from Mexico; C. doda from
      Mexico, Nicaragua and Costa Rica; C. carinipennis from Mexico and Guatemala; C.
      rileyi from Mexico, Honduras, and Belize, and C. wilsoni from Costa Rica. These
      species are figured, along with the type of C. kolbei Schenkling, and a lectotype
      is designated for the latter. I include a brief discussion on the prevalence and
      evolution of brachyptery in Cymatodera. 

PMID- 25947708
TI  - New and little known species of oribatid mites of the subgenus Galumna (Galumna)
      (Acari, Oribatida, Galumnidae) from Vietnam.
AB  - Two new species of oribatid mites of the subgenus Galumna (Galumna) (Acari,
      Oribatida, Galumnidae) are described from soil and litter of forest zones of
      southern Vietnam. Galumna (G.) paramastigophora sp. nov. differs from known
      species of calcicola-group by the morphology of bothridial setae and length of
      interlamellar setae; also, the new species is similar morphologically to
      Leptogalumna (Aegyptogalumna) mastigophora, however, it differs from the latter
      by the presence of lamellar lines, morphology of interlamellar setae and absence
      of notogastral setae. Galumna (G.) pseudotriquetra sp. nov. is similar
      morphologically to Galumna (G.) triquetra, however, it differs from the latter by
      the length of lamellar setae, number of postanal porose areas and morphology of
      notogastral porose areas Aa. Supplementary description of Galumna (G.) aba and
      remarks to the original description of Galumna (G.) levisensilla are presented. 

PMID- 25947709
TI  - Two new feather mites of the genus Neocalcealges Orwig (Analgoidea:
      Trouessartiidae) from the Sichuan province of China.
AB  - Two new species of the feather mite genus Neocalcealges Orwig 1968 (Analgoidea:
      Trouessartiidae) are described from passerine birds (Passeriformes) from the
      Sichuan province of China: Neocalcealges davidi sp. nov. from Alcippe davidi
      Styan (Leiothrichidae) and N. chrysotis sp. nov. from Lioparus chrysotis (Blyth)
      (Paradoxornithidae). We provide a key to all described species of Neocalcealges. 

PMID- 25947710
TI  - First record of the family Heloridae (Hymenoptera: Proctotrupoidea) from Iran,
      with description of a new species.
AB  - For the first time in more than 100 years, a new western Palaearctic species of
      Heloridae is described. Specimens of Helorus alborzicus Izadizadeh, van
      Achterberg & Talebi sp. nov. and Helorus ruficornis Forster were collected from
      the Alborz province of Iran. An illustrated identification key for Western
      Palaearctic Heloridae is provided. 

PMID- 25947711
TI  - On the spider genus Neonella (Araneae: Salticidae): new records and taxonomic
      notes for species from southern South America.
AB  - The genus Neonella Gertsch, 1936 contains 12 species with an exclusive New World
      distribution (World Spider Catalog 2015). The genus was proposed by Gertsch
      (1936) to include N. vinnula Gertsch, 1936 from Florida and Texas, USA. Remaining
      species were added by Galiano (1965, 1988, 1998) and, more recently, Edwards
      (2003), Ruiz & Brescovit (2004), and Ruiz et al. (2007). 

PMID- 25947712
TI  - Nomenclatural status of Euptychia mollina Hubner, 1818 (Lepidoptera: Nymphalidae:
      Satyrinae).
AB  - The purpose of this note is to clarify the nomenclatural status of Euptychia
      mollina Hubner, 1818, the type species of Euptychia Hubner, 1818, as there seems
      to be confusion regarding its year of publication. Due to an unfortunate
      oversight, Lamas (2004) listed the name as Euptychia mollina (Hubner, [1813]),
      and this mistake has been repeated in the subsequent literature (e.g. Brevignon
      2005; Warren et al. 2014; Neild et al. 2014). 

PMID- 25947713
TI  - Redescription and reclassification of the African termite, Forficulitermes
      planifrons (Isoptera, Termitidae, Termitinae).
AB  - Forficulitermes planifrons is a monotypic genus and species described by Emerson
      (1960) from three soldiers and a single worker. All known occurrences of
      Forficulitermes (Emerson 1960, Wango & Josens 2011, this study) originate from
      equatorial middle Africa. Emerson (1960) compared soldiers of Forficulitermes
      with Basidentitermes, Proboscitermes, Orthotermes, Profastigitermes, and
      Fastigitermes, (the latter all in the Cubitermitinae) with respect to the general
      shape of the labrum, but found no similarities among these genera with respect to
      either the former's mandibles or the undulating profile surrounding its
      fontanelle. The only worker morphology noted for F. planifrons by Emerson (1960)
      was a pair of worn mandibles. Based largely on the enteric valve armature, we
      herein redescribe F. planifrons and assign this genus to the subfamily
      Termitinae. 

PMID- 25947714
TI  - New records of Pseudophatnoma laosana B. Lis, 1999 (Hemiptera: Tingoidea:
      Cantacaderidae) from China and Thailand, with illustration of its male genitalia.
AB  - The lace-bug genus Pseudophatnoma was described for P. corniculata from the Riau
      Archipelago in Indonesia, and because of its morphological characteristics the
      genus was placed in the subfamily Cantacaderinae of the family Tingidae (Blote
      1945). 

PMID- 25947715
TI  - Aliocis, a replacement name for the preoccupied ciid genus Anoplocis Kawanabe,
      1996 (Coleoptera: Tenebrionoidea: Ciidae).
AB  - The Ciidae genus Anoplocis was established by Makoto Kawanabe (1996) based on the
      type species Ennearthron poriae Nakane & Nobuki, 1955 from Japan. Additionally,
      he described the Japanese species Anoplocis ryukyuensis Kawanabe, 1996. However,
      the name Anoplocis was previously proposed by Arthur M. Lea (1913) for a genus of
      true weevils (Coleoptera: Curculionidae), with its type species Anoplocis
      ferrugineus Lea, 1913 from Australia. In consequence, the genus Anoplocis
      Kawanabe, 1996 is a junior homonym of the genus Anoplocis Lea, 1913. According to
      Article 60 of the International Code of Zoological Nomenclature, we propose the
      replacement name Aliocis nom. nov. for Anoplocis Kawanabe, 1996. New combinations
      are here proposed for the two species included in this genus: Aliocis poriae
      (Nakane & Nobuki, 1955) comb. nov. and Aliocis ryukyuensis (Kawanabe, 1996) comb.
      nov. 

PMID- 25947716
TI  - The Crotonia fauna of New Zealand revisited (Acari: Oribatida): taxonomy,
      phylogeny, ecological distribution and biogeography.
AB  - New Zealand contains 13 of the 69 species of Crotonia described globally and is
      the only place where all three genera of the Crotoniinae-Crotonia, Austronothrus
      and Holonothrus-have been recorded. Due to the pioneering work of Hammer (1966)
      and Luxton (1982) it also has the highest number of distribution records of
      Crotonia spp. anywhere. In the present study I build upon previous work to re
      examine the Crotonia fauna of New Zealand in the light of recent taxonomic and
      biogeographical research. A new species is described, C. ramsayi sp. nov., a
      member of the Unguifera species group, and supplementary descriptions are
      provided for C. brachyrostrum (Hammer 1966), C. caudalis (Hammer, 1966), C.
      cophinaria (Michael, 1908), and C. unguifera (Michael 1908), as well as a key to
      species. Crotonia spp. from New Zealand occur predominantly in localities with
      relatively low mean annual temperature and high water balance, reflecting a
      requirement for cool, moist conditions. In New Zealand Crotonia spp. occur in an
      extremely wide variety of vegetation communities compared with other regions in
      its range (Australia, Africa and South America), and this is indicative that
      water balance requirements are met, regardless of vegetation type. Some elements
      of the New Zealand Crotonia fauna, notably the Cophinaria species group, are
      common to Australia, Africa and South America, indicating a shared evolutionary
      history pre-dating the separation of Africa from Gondwana 110 mya. The high
      proportion of species that occur west of the Alpine Fault is consistent with a
      relictual distribution of Gondwanan elements on the Australian Plate. However, it
      is unclear whether uplift of the Southern Alps formed a barrier to dispersal. A
      high representation of the morphologically closely-related Obtecta, Flagellata
      and Unguifera groups, shared only with South America (and, for Unguifera, with
      Oceania) represents a dramatically different faunal composition compared with
      other former Gondwanan landmasses and is consistent with submergence of most of
      New Zealand during the Oligocene (ca. 25 mya). All of these characteristics
      indicate a distinctive evolutionary pathway for the Crotonia fauna since New
      Zealand separated from the rest of Gondwana 80 mya. 

PMID- 25947717
TI  - Reassessment of the hairy long-nosed armadillo "Dasypus" pilosus (Xenarthra,
      Dasypodidae) and revalidation of the genus Cryptophractus Fitzinger, 1856.
AB  - The hairy long-nosed armadillo, currently referred as Dasypus (Cryptophractus)
      pilosus, is an enigmatic species endemic to montane cloud forests and subparamo
      of Peruvian Andes. Its strikingly different external features, which include the
      carapace concealed by abundant hair, the presence of more movable bands, and a
      slender skull, have raised questions regarding its taxonomic status as subgenus
      or as genus. This paper assesses this issue based on a cladistic study and
      provides a detailed comparative description of the species, including the first
      account on the distinctive ornamentation of its osteoderms. Based on several
      unique characters in the carapace, skull, mandible, and teeth, as well as on the
      external phylogenetic position relative to other Dasypus, we favor the assignment
      of the hairy long-nosed armadillo to other genus. As result, we revalidate the
      original generic epithet, so that the valid name of the species is Cryptophractus
      pilosus Fitzinger, 1856. 

PMID- 25947718
TI  - A new species of tree frog genus Rhacophorus from Sumatra, Indonesia Amphibia,
      Anura).
AB  - A small-sized tree frog of the genus Rhacophorus is described on the basis of 18
      specimens collected from three different localities on Sumatra Island, Indonesia.
      Rhacophorus indonesiensis sp. nov. is divergent from all other Rhacophorus
      species genetically and morphologically. The new species is distinguished from
      its congeners by a combination of: the presence of black spots on the ventral
      surfaces of the hand and foot webbing, an absence of vomerine teeth, a venter
      with a white kite-shaped marking, raised white spots on the dorsum or on the
      head, and a reddish brown dorsum with irregular dark brown blotches and distinct
      black dots. With the addition of this new species, fifteen species of Rhacophorus
      are now known from Sumatra, the highest number of species of this genus in the
      Sundaland region. However, with the increasing conversion of forest to oil palm
      cultivation or mining, the possibility of the extinction of newly described or as
      yet undiscovered species is of great concern. 

PMID- 25947719
TI  - Molecular phylogenetic relationships of the lizard clade Liolaemus elongatus
      (Iguania: Liolaemini) with the description of a new species from an isolated
      volcanic peak in northern Patagonia.
AB  - A new species of the Andean-Patagonian Liolaemus elongatus clade is described.
      Liolaemus crandalli sp. nov. differs from other members of its clade by a
      combination of coloration characters, scale counts and genetic traits. Liolaemus
      crandalli sp. nov. is known only from an isolated volcanic mountain in
      northwestern Patagonia above 1500 m.a.s.l. unconnected with other habitat
      suitable for species of the Liolaemus elongatus clade. 

PMID- 25947720
TI  - A new species of Cnemaspis (Sauria: Gekkonidae) from Northern Karnataka, India.
AB  - A new species of rupicolous gecko of the genus Cnemaspis is described from Hampi,
      Karnataka, southern India. Cnemaspis adii sp. nov. is diagnosable from all the
      Indian congeners in possessing the following suite of characters: medium-sized
      Cnemaspis, SVL less than 35 mm (31.7-34.9). Dorsal scales on the trunk
      homogeneous, small, granular and feebly keeled. Spine-like tubercles absent on
      the flanks. Mental subtraingular, two pairs of postmentals, primary pair
      separated by a single chin shield. Ventral scales on the trunk smooth, imbricate;
      22-26 scales across the belly. Supralabial I narrowly in contact with nasal.
      Dorsal aspect of forelimbs and hindlimbs are weakly unicarinate. Lamellae under
      the digit IV of pes 20-22. Males with two precloacal pores, two femoral pores on
      each side of the thigh. The existence of the species in a World Heritage Site
      with continuous anthropogenic interference ascertains the robustness of the
      species and need for additional herpetofaunal explorations to reveal the total
      diversity of species of the genus Cnemaspis in peninsular India. 

PMID- 25947721
TI  - A revision of the genus Pelecocera Meigen with the description of the male of
      pelecocera persiana Kuznetzov from Iran (Diptera: Syrphidae).
AB  - The genus Pelecocera Meigen (Diptera: Syrphidae) is revised. Type material of
      most species was studied to describe, illustrate and delimit the male of
      Pelecocera persiana Kuznetzov, recently discovered from Iran. This is the first
      known specimen of this species since 1914, when the type female was collected.
      The diagnostic characters of P. persiana are provided, along with an
      identification key for Pelecocera species. The lectotype of Pelecocera latifrons
      Loew is designated. 

PMID- 25947722
TI  - Revision of the genus Macrostomus Wiedemann (Diptera, Empididae, Empidinae). IV.
      The amazonensis species-group.
AB  - Six new species of Macrostomus Wiedemann are described, namely M. acreanus sp.
      nov. from Brazil (Acre state), M. amazonensis sp. nov. from Guyana and Brazil
      (Roraima, Amazonas, Para, Rondonia, and Mato Grosso states), M. albicaudatus sp.
      nov. from Brazil (Roraima, Amazonas, and Para states), M. paraiba sp. nov. from
      Brazil (Paraiba state), M. trombetensis sp. nov. from Brazil (Para state) and M.
      xavieri sp. nov. from Guyana and Brazil (Amazonas state). The six species are all
      treated in the M. amazonensis species-group, which is defined on the basis of one
      pair of ocellar setae and no supra-alar postsutural setae in combination with
      characters of the male and female terminalia. A key to the included species is
      presented and the geographical distributions of the species are mapped. 

PMID- 25947723
TI  - Three new species of genus Apotropina Hendel from China (Diptera, Chloropidae).
AB  - A review of the species of the genus Apotropina Hendel from China is provided.
      The following 3 species are described as new to science: A. bistriata sp. nov.,
      A. longiprocessa sp. nov. and A. tristriata sp. nov. A key to all species of
      Apotropina from the Oriental Region is given. 

PMID- 25947724
TI  - Tabasconura tapijulapana gen. nov. sp. nov. (Collembola: Neanuridae) from
      Tabasco, Mexico.
AB  - Tabasconura gen. nov. (Neanuridae) and type species T. tapijulapana sp. nov., are
      described and illustrated. The new genus possesses all characters of the tribe
      Sensillanurini Cassagnau, and is characterised by the presence of slightly
      elongated tubercles on the body and also elongation and thickening of the
      sensillum S2 as well as S7 on antennal segment IV. Development of S7 is a
      character of the tribe. 

PMID- 25947725
TI  - Description of the nymphs of Triatoma pintodiasi Jurberg, Cunha & Rocha, 2013
      (Hemiptera: Reduviidae: Triatominae).
AB  - Triatoma pintodiasi Jurberg, Cunha & Rocha, 2013 has been recently described
      based on material collected on Rio Grande do Sul State, Brazil. Nymphs of this
      species were unknown and their description might contribute for studies
      concerning the taxonomy, phylogeny, and evolution of the genus Triatoma. Such
      description is herein presented, along with comparison with other species of the
      rubrovaria subcomplex of species. 

PMID- 25947726
TI  - A review of the genus Phalgea Cameron (Hymenoptera: Ichneumonidae: Acaenitinae)
      with description of a new species from Vietnam.
AB  - In this paper, the genus Phalgea is reviewed. A new species, Phalgea maculata sp.
      nov., is described and illustrated  from Vietnam. In addition, P. melaptera Wang
      1989 is recorded as new for the country. It is the first time the subfamily
      Acaenitinae is reported from Vietnam. 

PMID- 25947727
TI  - Australasian ants of the subfamily Heteroponerinae (Hymenoptera: Formicidae): (2)
      the species-group of Heteroponera relicta (Wheeler),with descriptions of nine new
      species and observations on morphology, biogeography and phylogeny of the genus.
AB  - Workers and available gynes of Heteroponera relicta and nine new related
      morphospecies from northeast Queensland tropical rainforest are described in two
      species complexes: H. relicta (Wheeler), H. darlingtonorum, H. lioprocta, H.
      monteithi, H. rhodopygea, H. viviennae and H. wilsoni spp. n. (Heteroponera
      relicta complex); H. ecarinata, H. pendergrasti and H. trachypyx spp. n.
      (Heteroponera ecarinata complex). Known gynes (of 3 relicta-complex species) are
      flightless physogastric ergatoids. Biogeography and evolution of the group and of
      Heteroponera at large are reviewed. 

PMID- 25947729
TI  - Two new species of the genus Platambus Thomson, 1859 from China (Coleoptera:
      Dytiscidae, Agabinae).
AB  - One new species of the genus Platambus Thomson, 1859 from Ganzi Tibetan
      Autonomous Prefecture, Sichuan Province (P. brancuccii sp. n.) and one from
      Chengdu, Sichuan Province (P. korgei sp. n.) are described. They belong to the
      Platambus semenowi-group sensu Nilsson (2000). Important species characters
      (median lobes and colour patterns) of the two new species are figured, and notes
      on their distribution are given. Altogether seven species of the semenowi-group
      are now known from higher mountain regions in Central Asia, northern India,
      Nepal, Bhutan, Pakistan and China. Six of them are illustrated with habitus
      photos and a modified key to all species of the semenowi-group is presented. 

PMID- 25947728
TI  - Description of a new genus of ponyfishes (Teleostei: Leiognathidae), with a
      review of the current generic-level composition of the family.
AB  - In order to recognize a monophyletic taxonomy for Leiognathidae based on unique
      features of the bacterially mediated light-organ system, we describe a new
      sexually-dimorphic genus of elongate, shallow-bodied ponyfishes within the tribe
      Equulitini, which itself is recovered within the subfamily Gazzinae.
      Photolateralis, new genus, is unique among ponyfishes in possessing a translucent
      mid-lateral flank stripe, which depending on the species, may be either a
      composite "stripe" comprised of numerous independent translucent windows (P.
      stercorarius and P. moretoniensis), or a continuous translucent lateral stripe
      (P. antongil). This translucent lateral stripe is either lacking entirely in
      females, or is considerably less well developed. In contrast, males in its sister
      taxon, Equulites, are characterized by the presence of an expansive, triangular,
      translucent lateral flank patch that also exhibits species-specific morphology.
      Internally, in Photolateralis the light organ system is characterized by a
      moderately enlarged, donut-shaped, and conspicuously spotted light organ in males
      that extends only slightly posteriorly into the gas bladder. In contrast, in
      members of Equulites the dorsolateral lobes of the light organ in males are
      greatly enlarged, heavily pigmented, and extend posteriorly well into the gas
      bladder. In addition, internally male members of Photolateralis exhibit lateral
      clearing of the silvery gas bladder lining posteriorly, corresponding in extent
      to the external translucent lateral stripe or windows on the flank. Including the
      new genus described herein, we now recognize 10 monophyletic genera of extant
      ponyfishes. 

PMID- 25947730
TI  - More of the same: a diminutive new species of the Limnonectes kuhlii complex from
      northern Vietnam (Anura: Dicroglossidae).
AB  - A new species in the dicroglossid genus Limnonectes known only from Ha Giang
      province, Vietnam is described. Analysis of DNA sequence data from the
      mitochondrial 12S and 16S gene regions places the species within the Limnonectes
      kuhlii Complex and demonstrates it to be the sister taxon to an Indochinese clade
      containing L. isanensis, L. jarujini, L. megastomias, and L. taylori. The new
      species occurs in syntopy with L. bannaensis. Both molecular and morphological
      data support the recognition of this lineage as a new species. Notably, the
      relatively diminutive size of this species distinguishes Limnonectes nguyenorum
      sp. nov. from all other members of the L. kuhlii Complex. 

PMID- 25947731
TI  - Review of the paper wasps of the Parapolybia indica species-group (Hymenoptera:
      Vespidae, Polistinae) in eastern parts of Asia.
AB  - Nine species of the Parapolybia indica species-group in eastern parts of Asia are
      reviewed. Four new species are described: P. flava sp. nov. (Vietnam), P. crocea
      sp. nov. (Japan), P. nana sp. nov. (Vietnam), and P. albida sp. nov. (Vietnam).
      Parapolybia indica (de Saussure, 1854), P. bioculata van der Vecht, 1966 and P.
      tinctipennis (Cameron, 1900) are redescribed. The status is reinstanted for P.
      fulvinerva (Cameron, 1900), stat. resurr. and P. tinctipennis (Cameron, 1900),
      stat. resurr. and new status is proposed for P. bioculata van der Vecht, 1966,
      stat. nov. Parapolybia tinctipennis (Cameron, 1900) is newly recorded from China,
      Vietnam and Laos. The key to species is given. The nests of P. indica, P.
      bioculata, P. tinctipennis, P. flava and P. crocea are remarked. 

PMID- 25947733
TI  - On Afrotropical Mohelia Matile (Diptera, Mycetophilidae): new species and
      phylogenetic comments.
AB  - Mohelia was originally described by Matile for M. nigricauda, from the Comoros.
      Three new Afrotropical species of Mohelia are described. The male and female
      terminalia of M. matilei sp.n., M. amorimi sp.n., and M. chandleri sp.n. are
      illustrated. An additional species, not formally described, is commented on. An
      identification key is also provided, as well as a distribution map for the genus.
      The differences between Mohelia and Aphrastomyia Lane & Coher are also discussed.

PMID- 25947732
TI  - Three new species of Quedius elpenor group (Coleoptera: Staphylinidae:
      Staphylinini: Quediina) from China.
AB  - Three new species of the subgenus Distichalius Casey, 1915 of the genus Quedius
      Stephens, 1829 are described based on specimens collected in China: Q.
      (Distichalius) biprominulus sp. nov., Yunnan; Q. (Distichalius) fusus sp. nov.,
      Beijing; and Q. (Distichalius) paululus sp. nov., Sichuan. The new species belong
      to the Quedius elpenor group and increase the number of species of this group to
      10. Line drawings and color illustrations of adults and genitalia of the new
      species are given. A key to all species of this group is provided and their
      geographical distribution is mapped. 

PMID- 25947734
TI  - A new species of Afropinnotheres Manning, 1993 (Crustacea, Brachyura,
      Pinnotheridae) from southwestern India, the first record of the genus from the
      Indian Ocean, with a review of the Pinnotheridae of India and adjacent seas.
AB  - A new species of pinnotherid crab of the genus Afropinnotheres Manning, 1993, is
      described from the brown mussel, Perna perna (Linnaeus, 1758), in southwestern
      India. This is the first record of the genus from the western Indian Ocean, the
      other four species been recorded from the eastern Atlantic. The new species can
      be distinguished from all congeners in  possessing a more rounded male carapace,
      form of the chela, relatively longer ambulatory legs which have no natatory
      setae, presence of dense pubescence on the male ambulatory legs, and the shape of
      the male and female telsons. The Indian Pinnotheridae is also reviewed and the
      taxonomy of the species reappraised. The taxonomy of Pinnaxodes Heller, 1865, and
      Holothuriophilus Nauck, 1880, is also discussed, in the context of their
      similarity to Afropinnotheres. 

PMID- 25947735
TI  - Amazonimyia gigantea gen. n., sp. n., a new Tanypodinae (Diptera: Chironomidae)
      from the Neotropical Region.
AB  - A new genus, Amazonimyia, is established for a species of the tribe Pentaneurini
      (Diptera, Chironomidae, Tanypodinae) from the Amazon Rainforest in northern
      Brazil. Generic diagnoses for adult male and pupa are provided together with
      descriptions of a new species, Amazonimyia gigantea. 

PMID- 25947736
TI  - Description of a new species and species-group of Sphaeropthalma Blake
      Hymenoptera: Mutillidae) with an updated classification of the genus.
AB  - A study of Sphaeropthalma Blake from the southwestern USA has revealed a highly
      autapomorphic undescribed species. This species is described here as S. tapio
      Pitts & Sadler, sp. nov., and is placed in a new species-group, the S. tapio
      species-group. This species seems to be found only at higher altitudes in
      southern Arizona. It is compared to other similar Sphaeropthalma species-groups
      and is likely most closely related to members of the S. imperialis species-group.
      An updated species-group classification of Sphaeropthalma is provided. 

PMID- 25947737
TI  - A new species of free-living marine nematode (Nematoda: Chromadoridae) from the
      East China Sea.
AB  - A new species of free-living marine nematodes, Ptycholaimellus longibulbus sp.
      nov., is described from the East China Sea. Ptycholaimellus longibulbus sp. nov.
      is characterized by having body length of about 1100-1400 MUm, cephalic seta 9 um
      long (half a head diameter), a relatively long double posterior pharyngeal bulb
      occupying 44-49% of pharyngeal length, a voluminous ventral gland with a large
      ampulla, cuticle with transverse rows of punctations and lateral differentiation
      with two longitudinal rows of thick dots, relatively long spicules 45-55 MUm
      long, an arcuate gubernaculum 25 um long, and a conico-cylindrical tail with a
      distinct long finger-like spinneret. A key to species of Ptycholaimellus is
      given. 

PMID- 25947738
TI  - The Thrips formosanus group from Asia and Australia with a new species of the
      genus Thrips (Thysanoptera: Thripidae) from India.
AB  - A new species-group in the genus Thrips is designated as Thrips formosanus group
      from Asia and Australia. This includes the following six species: T. floreus
      Kurosawa from Japan, T. formosanus Priesner from Taiwan, T. obscuripes Priesner
      and T. rostratus Priesner from Java, T. tanicus Bhatti from India and T. hoddlei
      Mound and Masumoto from Australia. One new species, Thrips moundi sp. n., is
      described in this group from specimens collected on grasses in Himachal Pradesh
      State of India. A key to the seven species of Thrips formosanus group is also
      provided. Partial sequence data for the gene mitochondrial cytochrome <span
      style="text-decoration: underline;">c oxidase (mtCOI) from the holotype and
      paratype of this new species is provided. 

PMID- 25947739
TI  - The complete larval development of Pagurus maculosus Komai & Imafuku, 1996
      (Decapoda, Anomura, Paguridae) reared in the laboratory, and a comparison with
      sympatric species.
AB  - The complete larval development of the hermit crab Pagurus maculosus, is
      described and illustrated based on specimens reared in the laboratory at 15 
      degrees C and 33-35 PSU. Newly hatched larvae invariably passed through a short
      prezoeal stage (10 minutes to 2 hours), four zoeal stages (each of 7 days,) and
      one megalopal stage (14 days). Distinct morphological features of each larval
      stage of the present study are compared with other closely related species in
      Japanese waters, and we found many differences in morphology and the duration of
      zoeal stages between them. We mentioned significant diagnostic characters
      separating this species from other congeners in Japanese waters that include the
      presence of red-yellowish chromatophores on the maxillipeds. This is the first
      report of complete larvae development of Pagurus maculosus.

PMID- 25947740
TI  - Hermit crabs from Brazil: Family Diogenidae (Crustacea: Decapoda: Paguroidea),
      except Paguristes.
AB  - We present here the genera and species of the family Diogenidae recorded from
      Brazil, with the exception of the genus Paguristes. We provide a diagnosis,
      synonymy and illustrations for each species of the nine genera from Brazil and
      identification keys for genera represented by more than one species. 

PMID- 25947741
TI  - Systematics of the endangered toad genus Andinophryne (Anura: Bufonidae):
      phylogenetic position and synonymy under the genus Rhaebo.
AB  - Bufonidae is one of the most diverse amphibian families. Its large-scale
      phylogenetic relationships are relatively well understood with the exception of
      few Neotropical genera that may have diverged early in the evolution of the
      family. One of those genera is Andinophryne, a poorly known group of three toad
      species distributed in the western slopes of the Andes of northern Ecuador and
      southern Colombia. Their phylogenetic position is unknown due to lack of genetic
      data. We estimated a new phylogeny (over 200 species) of the family Bufonidae
      based on DNA sequences of mitochondrial and nuclear genes to assess the
      phylogenetic position of Andinophryne based on recently collected specimens of A.
      colomai and A. olallai from Ecuador and Colombia. We also examined external and
      internal morphology of Andinophryne to explore its congruence with the new
      phylogeny. The mtDNA and nuclear phylogenies show that Andinophryne is embedded
      within Rhaebo, a genus that belongs to a large clade characterized by the
      presence parotoid glands. Morphological characters confirmed the affinity of
      Andinophryne to Rhaebo and a close relationship between Andinophryne colomai and
      Andinophryne olallai. Rhaebo was paraphyletic relative to Andinophryne and to
      solve this problem we synonymize Andinophryne under Rhaebo. We discuss putative
      morphological synapomorphies for Rhaebo including Andinophryne. We provide
      species accounts for R. atelopoides new comb., R. colomai new comb. and R.
      olallai new comb. including assessments of their conservation status. We suggest
      that the three species are Critically Endangered. Their altitudinal distribution
      and association with streams are characteristic of endangered Andean amphibians. 

PMID- 25947742
TI  - A new species of Cephalodasys (Gastrotricha, Macrodasyida) from the Caribbean Sea
      with a determination key to species of the genus.
AB  - A new marine gastrotrich species of the genus Cephalodasys is described from
      shallow sublittoral coralline sand sampled between Lee Stocking Island and
      Norman's Pond Cay (Exuma Cays), Bahamas. Cephalodasys interinsularis n. sp.
      reaches a body length of 471 um and is characterized by a new combination of
      characters including six total anterior adhesive tubes and five pairs of
      ventrolateral adhesive tubes. The new species is morphologically similar to C.
      swedmarki but can be distinguished by the different number of anterior adhesive
      tubes, the spatial arrangement of the ventrolateral adhesive tubes, and a shorter
      pharynx. We provide an updated diagnosis of the genus and a determination key to
      all known species of Cephalodasys. C. interinsularis n. sp. is the third known
      species of Cephalodasys from the Caribbean marine province. 

PMID- 25947743
TI  - A new species of Erythrodiplax breeding in bromeliads in Costa Rica (Odonata:
      Libellulidae).
AB  - We describe a new species, Erythrodiplax laselva (Libellulidae), that breeds in
      bromeliads and Cochliostema (Commelinaceae) in the eastern lowlands of Costa
      Rica. The closest known relative is thought to be E. castanea, widespread in
      Central and South America, and not E. bromeliicola, which is known to breed in
      bromeliads in Cuba and Jamaica. The male, female, genitalia, and larva are
      described and illustrated. 

PMID- 25947744
TI  - Arge pyracanthae n. sp. (Hymenoptera: Argidae) feeding on Pyracantha fortuneana
      in Hunan Province, China.
AB  - Arge pyracanthae Wei & Shinohara, n. sp. is described from Mt. Hupingshan, Hunan
      Province, China, including COI sequences from two specimens. Larvae are solitary
      external leaf feeders on Pyracantha fortuneana (Maxim.) H. L. Li (Rosaceae).
      Field observations and rearing experiments showed that this species has a
      multivoltine life cycle. This is the first record of an argid sawfly associated
      with Pyracantha. 

PMID- 25947745
TI  - Description of two new species of Martarega White, 1879 (Heteroptera: Nepomorpha:
      Notonectidae), one based on the mixed type-series of M. oriximinaensis Barbosa,
      Ribeiro & Ferreira-Keppler, 2010.
AB  - Description of two new species of Martarega White, 1879 (Heteroptera: Nepomorpha:
      Notonectidae), one based on the mixed type-series of M. oriximinaensis Barbosa,
      Ribeiro & Ferreira-Keppler, 2010. Martarega currently includes 20 species
      restricted to the Americas. A mixed type-series of M. oriximinaensis from Brazil
      was detected, including males with an additional group of ensiform bristles on
      the fore trochanter and mesofemur conspicuously setose. These specimens were
      described as a new species, M. siolii Barbosa, Nessimian & Takiya, sp. nov., and
      a redescription of M. oriximinaensis is also given. A second new species from
      Colombia is described, M. guajira Barbosa, Nessimian & Takiya, sp. nov. This
      species is very similar to M. pacifica, except for having groups of ensiform
      setae on the fore- and mesotrochanter, and an additional opaque area on the
      hemelytra. 

PMID- 25947746
TI  - Two new Otoplanid species (Platyhelminthes: Rhabditophora: Proseriata) of the
      genera Orthoplana Steinbock, 1932 and Postbursoplana Ax, 1956 from the Tuscan
      coast (Italy).
AB  - Two new species of marine flatworms, collected on the sandy shores of Tuscany,
      are described. These species exhibit the morphological characteristics of the
      subfamilies Otoplaninae and Parotoplaninae ("Turbellaria", Otoplanidae), but
      clearly differ from other described species. Orthoplana lunae sp. nov., is
      characterized by a body length of 1.4-1.6 mm, distinctive features of the testes
      and vitellaries, the male sclerotic apparatus composed of a median stylet (48-49
      MUm long), and 19 spines (17-44 MUm long). Postbursoplana donoraticensis sp.
      nov., is characterized by a body length of 1.6-1.8 mm, the distribution of testes
      and vitellaries, the male sclerotic apparatus composed of 10 spines (46-70 MUm).
      This new species has a greater body length relative to other species in this
      genus. They were collected along the sandy shores at low water mark at Partaccia
      (Marina di Massa, Ligurian Sea, Italy) and Marina di Donoratico (Livorno,
      Ligurian Sea, Italy), respectively. 

PMID- 25947747
TI  - A new species of Saurida (Pisces: Synodontidae) from the Mascarene Plateau,
      Western Indian Ocean.
AB  - A new species of lizardfish, Saurida tweddlei n.sp., from the Mascarene Plateau,
      Western Indian Ocean, is described and figured. The new species is characterised
      by the following combination of characters: dorsal fin with 12-13 rays; pectorals
      with 14-15 rays; lateral-line scales 53-55; transverse scale rows above lateral
      line 41/2, below lateral line 51/2; pectoral fins moderately long (extending to
      or just beyond a line from origin of pelvic fins to origin of dorsal fin); 2 rows
      of teeth on outer palatines; 0-3 teeth on vomer; tongue with about 4-5 rows of
      teeth posteriorly; caudal peduncle compressed (depth greater than width); stomach
      and intestine pale whitish. A key to the species of Saurida of the Western Indian
      Ocean is provided. 

PMID- 25947748
TI  - Evaluating recent taxonomic changes for alligator snapping turtles (Testudines:
      Chelydridae).
AB  - The Alligator Snapping Turtle (Macrochelys temminckii Troost in Harlan 1835,
      sensu lato) has been historically treated as a single, wide-ranging species,
      until a recently published paper by Thomas et al. (2014; hereafter Thomas et al.)
      analyzed variation in morphology and mitochondrial DNA sequence data to describe
      two new species of Macrochelys: the Apalachicola Alligator Snapping Turtle
      (Macrochelys apalachicolae Thomas, Granatosky, Bourque, Krysko, Moler, Gamble,
      Suarez, Leone & Roman 2014) and the Suwannee Alligator Snapping Turtle
      (Macrochelys suwanniensis Thomas, Granatosky, Bourque, Krysko, Moler, Gamble,
      Suarez, Leone & Roman 2014). The specific epithet temminckii was retained for
      populations in drainages from the Yellow River in Alabama and Florida west to the
      San Antonio River, Texas. Because populations of Macrochelys have been
      historically exploited by humans (Pritchard 1989) and the life-history strategies
      of large, long-lived turtles make them susceptible to declines from harvest
      (Congdon et al. 1994), a sound understanding of species delimitation and richness
      is critical for the conservation of alligator snapping turtles, especially if the
      acceptance of a widely distributed species disguises the presence of multiple,
      smaller-ranged species. 

PMID- 25947749
TI  - Five Sarsiellidae ostracods (Crustacea: Myodocopida) from the South Coast of
      Korea (East China Sea).
AB  - The East China Sea is part of the Warm Temperate Northwest Pacific zoogeographic
      province and, as such, has a high biodiversity and many tropical and subtropical
      biotic elements. Nevertheless, many invertebrate groups from this area remain
      poorly studied. Ostracods are one of them, especially those belonging to the
      subclass Myodocopa. In this paper we provide the first data on a diverse
      myodocopid family, Sarsiellidae, not only for the East China Sea, but also for
      Korea. Five species are reported in this paper from three Korean islands (Jeju,
      Chuja, and Maemul), and they are only a part of the ostracods collected during
      this study, indicating a high diversity of the group in this region. Three new
      species, Eurypylus koreanus sp. nov., Eusarsiella hanguk sp. nov., and Sarsiella
      nereis sp. nov., clearly stand apart from their respective congeners, mostly by
      prominent shell characters but also by details of the soft part morphology. Their
      affinity though clearly indicates a close connection of the region with the more
      southern zoogeographical realms, especially Central Indo Pacific and partly
      Temperate Australasia. Two species previously known from Japan (north part of the
      Sea of Japan and southeastern part of the Pacific Coast of Japan), Sarsiella
      japonica Hiruta, 1977 and S. misakiensis Kajiyama, 1912, are redescribed. Based
      on 11 newly obtained COI sequences we construct a preliminary phylogenetic tree,
      which supports previous hypotheses based on the morphological data, that
      Eusarsiella Cohen & Kornicker, 1975 is a polyphyletic taxon. With the maps of
      species distribution provided for each of the three genera, we give an overview
      of their current zoogeography, and clearly indicate areas that have no data,
      mostly due to the lack of investigation. 

PMID- 25947750
TI  - Six new species of the planthopper genus Usana Distant, 1906 (Hemiptera:
      Fulgoromorpha: Achilidae) from China.
AB  - Six new species of the planthopper genus Usana, U. aspergilliformis sp. nov., U.
      concava sp. nov., U. congjiangensis sp. nov., U. fissura sp. nov., U.
      oblongincisa sp. nov. and U. unispina sp. nov. are described and illustrated from
      China. A checklist, a key to all species of the genus and illustrations of U.
      lineolalis Distant, 1906 are also given. 

PMID- 25947751
TI  - Microdrile Oligochaeta in bromeliad pools of a Honduran cloud forest.
AB  - Phytotelmata, or plant-held water bodies, often house complex aquatic
      invertebrate communities. Microdrile oligochaetes (Clitellata, Annelida) are
      known to be part of that community, but specimens are rarely identified to
      species level. Here we report three species of Enchytraeidae and three species of
      Naididae from a collection sampled in phytotelms of bromeliads in Cusuco National
      Park, Honduras. Two species of enchytraeids are new to science. Bryodrilus
      hondurensis sp. nov. is distinguished from other members of the genus by the high
      number of ventral chaetae, up to 11 per bundle. The genus is Holarctic and this
      is the southernmost record so far of a Bryodrilus species. Hemienchytraeus
      phytotelmatus sp. nov. is distinguished by a combination of characters, among
      which the huge spermathecae and seminal vesicles are most conspicuous. The genus
      is common in tropical and subtropical soils around the world. A third species of
      enchytraeids in the collection, Cernosvitoviella atrata (Bretscher), is
      redescribed, together with three known species of Naididae, Pristina jenkinae
      (Stephenson), Pristina osborni (Walton) and Pristina terrena Collado & Schmelz.
      Presence of ingested debris and humus in the intestine of most specimens suggests
      that the collected animals live and reproduce in the phytotelms. We provide a
      list of oligochaete species recorded so far from bromeliad pools in Central and
      South America. 

PMID- 25947752
TI  - A preliminary study on the phylogeny of the family Phengodidae (Insecta:
      Coleoptera).
AB  - A morphology-based phylogenetic analysis of the family Phengodidae (Coleoptera)
      is given. Thirty-six terminals, six genera and 60 morphological characters are
      included. To test the monophyly of phengodid subfamilies the terminals that
      belong to superfamily Elateroidea Drilocephalus Pic (Dascillidae), Pterotus
      LeConte (incertae sedis), Vesperelater Costa (Elateridae), Photinus Laporte
      (Lampyridae), Pseudotelegeusis Wittmer and Telegeusis Horn (Telegeusidae) are
      used as outgroups, with the remaining 30 terminals corresponding to 26 specific
      and four generic levels. The matrix was analyzed under a parsimony criterion
      under a heuristic search performed in TNT v. 2.0. One parsimonious tree was
      obtained. In this study two principal groups are recognized in the family
      Phengodidae. This study suggests for the first time a close relationship between
      the Telegeusidae and the subfamily Penicillophorinae. 

PMID- 25947753
TI  - First report of Dermatopelte Erdos & Novicky (Hymenoptera, Eulophidae) from the
      Indo-Malayan realm, with descriptions of new species.
AB  - Four new species of Dermatopelte Erdos & Novicky (Hymenoptera, Eulophidae), D.
      bavilucus n. sp., D. collis n. sp., D. hanoica n. sp. and D. heratyi n. sp., are
      described from the Indo-Malayan biogeographic realm, the first three based on
      females and the last on a male. While similar to previously described Nearctic
      and Palearctic species, these new species comprise a distinct species group
      defined by a stronger transverse pronotal carina and smooth propodeal median
      panels. The differences between Indo-Malayan, Nearctic, and Palearctic species of
      Dermatopelte are discussed, and a key to all species of the genus is provided. 

PMID- 25947754
TI  - A second Eocene species of death-watch beetle belonging to the genus Microbregma
      Seidlitz (Coleoptera: Bostrichoidea) with a checklist of fossil Ptinidae.
AB  - Based on a well-preserved specimen from Upper Eocene Baltic amber (Kaliningrad
      region, Russia), Microbregma waldwico sp. nov., the second fossil species of this
      genus, is described. The new species is similar to the extant Holarctic M.
      emarginatum (Duftschmid), 1825, and fossil M. sucinoemarginatum (Kuska), 1992,
      but differs in its shorter abdominal ventrite 1 (about 0.43 length of ventrite 2)
      and larger body (5.1 mm). A key to species of the genus Microbregma is given, and
      a check-list of described fossil Ptinidae is provided. The fossil record of
      Ptinidae now includes 48 species in 27 genera and 8 subfamilies. 

PMID- 25947755
TI  - Three new species of Polypedilum Kieffer (Diptera: Chironomidae) from Neotropical
      region.
AB  - Three new species of Polypedilum from Brazil, belonging to subgenera Tripodura
      and Pentapedilum are described and illustrated. P. (Pe.) puri sp. n. and P. (Tr.)
      guato sp. n. are described based on male adults and P. (Tr.) kadiweu sp. n. on
      male adult, pupa and larva. 

PMID- 25947756
TI  - Description of Sectonema septentrionale sp. n. (Nematoda: Dorylaimida:
      Aporcelaimidae) from Northern Iberian Peninsula.
AB  - A new species of the genus Sectonema, collected from natural forests in the
      Spanish provinces of Leon and Palencia, is described and illustrated with line
      drawings and LM pictures. Sectonema septentrionale sp. n. is characterized by its
      5.59-6.90 mm long body, lip region 25-29 MUm broad and offset by deep
      constriction, mural tooth 18-19 MUm long at its ventral side and occupying most
      of the stomatal lumen, pharyngeal expansion 618-926 MUm long or 60-73% of total
      neck length, uterus tripartite and 370-493 MUm long or 2.9-4.3 times the
      corresponding body diameter, V = 48-52, tail short and rounded (40-62 MUm, c =
      108-146, c' = 0.6-0.8), spicules 100-145 MUm long, and 5-11 irregularly spaced
      ventromedian supplements with hiatus. It is very close to S. demani, but differs
      both in the nature of the mural tooth and of the uterus. 

PMID- 25947757
TI  - Review and three new species of the flat bug genus Neochelonoderus Hoberlandt,
      1967 from East Africa (Hemiptera: Heteroptera: Aradidae).
AB  - The apterous East African Mezirinae flat bug genus Neochelonoderus Hoberlandt
      1967 is revised. In addition to known species from Burundi (N. basilewskyi) and
      Democratic Republic of the Congo (N. straeleni), two new species from Tanzania
      (N. talaus n. sp. and N. areius n. sp.) and one from Zambia (N. hoberlandti n.
      sp.) are described and illustrated. A key to the species of Neochelonoderus is
      presented. 

PMID- 25947758
TI  - A new species of the genus Orchesia Latreille (Coleoptera: Melandryidae) from
      Baltic amber with a key to species described from fossil resins.
AB  - Orchesia (Orchestera) canaliculata sp. nov. is described and illustrated from
      Eocene Baltic amber (Kaliningrad Region, Russia). New fossil records on O.
      turkini Alekseev & Bukejs and O. rasnitzyni Nikitsky are presented. A key to
      species of Orchesia Latreille, described from fossil resins, is provided. 

PMID- 25947759
TI  - Forgotten records of Chrysopelea taprobanica Smith, 1943 (Squamata: Colubridae)
      from India.
AB  - The colubrid snake Chrysopelea taprobanica Smith, 1943 was described from a
      holotype from Kanthali (= Kantalai) and paratypes from Kurunegala, both
      localities in Sri Lanka (formerly Ceylon) (Smith 1943). Since its description,
      literature pertaining to Sri Lankan snake fauna considered this taxon to be
      endemic to the island (Taylor 1950, Deraniyagala 1955, de Silva 1980, de Silva
      1990, Somaweera 2004, Somaweera 2006, de Silva 2009, Pyron et al. 2013). In
      addition, earlier efforts on the Indian peninsula (e.g. Das 1994, 1997, Das 2003,
      Whitaker & Captain 2004, Aengals et al. 2012) and global data compilations (e.g.
      Wallach et al. 2014, Uetz & Hosek 2015) did not identify any record from mainland
      India until Guptha et al. (2015) recorded a specimen (voucher BLT 076 housed at
      Bio-Lab of Seshachalam Hills, Tirupathi, India) in the dry deciduous forest of
      Chamala, Seshachalam Biosphere Reserve in Andhra Pradesh, India in November 2013.
      Guptha et al. (2015) further mentioned an individual previously photographed in
      2000 at Rishi Valley, Andhra Pradesh, but with no voucher specimen collected.
      Guptha's record, assumed to be the first confirmed record of C. taprobanica in
      India, is noteworthy as it results in a large range extension, from northern Sri
      Lanka to eastern India with an Euclidean distance of over 400 km, as well as a
      change of status, i.e., species not endemic to Sri Lanka. However, at least three
      little-known previous records of this species from India evaded most literature
      and were overlooked by the researchers including ourselves. 

PMID- 25947761
TI  - Description of six new species of Anomalini from Costa Rica (Coleoptera:
      Scarabaeidae: Rutelinae).
AB  - Four new species of Anomala Samouelle and two new species of Callistethus
      Blanchard (Coleoptera: Scarabaeidae: Rutelinae: Anomalini) from Costa Rica are
      described: A. aglaos new species, A. estrella new species, A. inbio new species,
      A. pincelada new species, C. ruteloides new species, and C. yalizo new species. A
      distribution map of each species is given and the male genitalia (aedeagus and
      endophallus) of the species described and similar species are illustrated. 

PMID- 25947760
TI  - An integrative taxonomic review of the agamid genus Bronchocela (Kuhl, 1820) from
      Peninsular Malaysia with descriptions of new montane and insular endemics.
AB  - An integrative taxonomic analysis is used to identify and describe two new
      species of the agamid genus Bronchocela (Kuhl) from Peninsular Malaysia: an
      upland species B. shenlong sp. nov. from Bukit Larut, Perak in the Bintang
      Mountain Range and Parit Falls, Cameron Highlands, Pahang in the Titiwangsa
      Mountain Range and an insular species, B. rayaensis sp. nov., from Pulau
      Langkawi, Kedah off the northwest coast on the border with Thailand. Both species
      are diagnosed from each other and all other species of Bronchocela on the basis
      of body shape, scale morphology, and color pattern. The analysis also
      demonstrates the remarkable genetic similarity of B. cristatella (Kuhl)
      throughout 1120 km of its range from northern Peninsular Malaysia to western
      Borneo despite its highly variable coloration and pattern. The two new species
      are appended to a rapidly growing list of newly described lizard species (60 to
      date) from Peninsular Malaysia tallied within the last decade. 

PMID- 25947762
TI  - Taxonomy of the water beetle genus Limnebius Leach in southern Africa
      (Coleoptera:  Hydraenidae).
AB  - The southern African species of the water beetle genus Limnebius Leach, 1815, are
      revised. Eleven new species are described, based on the examination and
      databasing of 6,201 specimens from 96 localities/events. Male genitalia are
      illustrated, and high resolution habitus images of the holotypes are provided.
      Distribution maps are provided for the eleven species now known from southern
      Africa, including Namibia, South Africa, Zambia, Zimbabwe, and the extreme
      southern part of Angola. New species of Limnebius are: L. capensis (South Africa:
      Western Cape Province, W. Cape, Hawequas); L. convexus (South Africa: Western
      Cape Province, Little Karroo, Raubenheimer Dam); L. endroedyi (Namibia: C. Namib
      desert, Numis Wasser); L. kavango (Namibia: Kavango: Mahango Game Reserve); L.
      masculinus (South Africa: KwaZulu-Natal Province, Hluhluwe Game Reserve); L.
      probus (South Africa: KwaZulu-Natal Province, Zululand, Dukuduku Forest Station);
      L. quantillus (South Africa: Limpopo Province, N. Transvaal, Mmabolela estate);
      L. retiolus (South Africa: Northern Cape Province, Cape Farm Ezelsfontein); L.
      speculus (South Africa: KwaZulu-Natal Province, Hluhluwe Game Reserve); L.
      suaviculus (South Africa: KwaZulu-Natal Province, Tugela River near Olivershoek
      road); L. transversus (South Africa: KwaZulu-Natal Province, Mtubatuba). 

PMID- 25947763
TI  - A new species of Indian caecilian highlights challenges for species delimitation
      within Gegeneophis Peters, 1879 (Amphibia: Gymnophiona: Indotyphlidae).
AB  - A new species of indotyphlid caecilian amphibian, Gegeneophis tejaswini sp. nov.,
      is described based on eight specimens from lowlands of the most northerly
      district of the state of Kerala in the southern part of the Western Ghats region,
      India. This species is distinguished from all other Gegeneophis in annulation
      characters and genetics (> 6% different from most similar nominal species for 883
      base pairs of mitochondrial 12S and 16S rRNA gene sequence data). The high degree
      of morphological similarity of G. krishni, G. mhadeiensis and the new species
      underlines that, for some Gegeneophis, larger samples and/or new characters will
      be needed to further advance the taxonomy of this genus. 

PMID- 25947764
TI  - Catalogue of Dictyoptera from Syria and neighbouring countries (Lebanon, Turkey,
      Iraq and Jordan).
AB  - This study is a catalogue of Dictyoptera (Mantodea, Isoptera and Blattaria) from
      five Eastern Mediterranean countries (Syria, Lebanon, Turkey, Iraq and Jordan).
      There are 75 species of Dictyoptera known to occur in these countries. These
      species belong to 15 families (eight of Mantodea, four of Isoptera and three of
      Blattaria). Mantodea is by far the dictyopteran group with the highest richness
      with 43 species occurring in this region, followed by Blattaria, with 21, and
      Isoptera with 11. Turkey is the place with the highest number of Dictyoptera
      (34%), followed by Iraq (23%) then Syria (22%), Jordan (15%) and Lebanon (7%). An
      analysis of accumulated number of species along time shows that most of this
      biodiversity was described during the 20th century, and that Mantodea is the
      group with the highest number of species described more recently. If this curve
      is taken as an estimator of the increase of diversity with new prospections, this
      indicates that the number of Mantodea in this region would be much higher than
      presently known. Conversely, the local richness of Blattaria and Isoptera are
      likely to be close to the present numbers, as the curves remain steady for about
      100 years. An accumulation curve of species described with occurrence restricted
      to these five countries shows that most of them were described at the beginning
      of the 20th century. An analysis of the number of references dealing with each of
      these species along time reveals that Mantodea is the dictyopteran group most
      studied in all periods except the second half of the 20th century, when Isoptera
      was more cited. The types of these species are distributed in 29 institutions,
      but are mainly concentrated in four major European collections.

PMID- 25947765
TI  - A survey of East Palaearctic Gnaphosidae (Araneae). 4. A review of Fedotovia
      Charitonov, 1946.
AB  - Fedotovia Charitonov, 1946 is a genus of Gnaphosinae earlier known to contain
      only two species: F. uzbekistanica Charitonov 1946 (??, type species) and F.
      mongolica Marusik, 1993 (?). Revision of available material reveals two more
      species, both from Mongolia: F. mikhailovi sp. n. (??) and F. feti sp. n. (??).
      All four species have very similar copulatory organs and can be more easily
      differentiated by somatic characters (body size, spination, eye formula). All
      species are described and illustrated. 

PMID- 25947766
TI  - Description of immatures associated with adults of two species of Macrogynoplax
      Enderlein and one species of Enderleina Jewett (Plecoptera: Perlidae) of the
      Brazilian Amazon.
AB  - Nymphs of Macrogynoplax delicata Ribeiro-Ferreira & Froehlich, 1999, M. pulchra
      Ribeiro-Ferreira & Froehlich, 1999, and E. froehlichi Ribeiro-Ferreira, 1996 were
      associated with adults by rearing and described for the first time. The known
      distribution of each species has been increased. 

PMID- 25947767
TI  - A new species and first record of Cotinis Burmeister (Coleoptera: Scarabaeidae:
      Cetoniinae) for Venezuela.
AB  - A new Cotinis Burmeister (Coleoptera: Scarabaeidae: Cetoniinae: Gymnetini)
      species from Venezuela is described and illustrated. The new species is compared
      with Cotinis barthelemyi (Gory & Percheron) from Colombia. The Neotropical
      distribution of Cotinis is expanded to Venezuela. A revised key to the species of
      Cotinis is provided in both English and Spanish. 

PMID- 25947768
TI  - Limnophyes guarani sp. n., a new hygropetric Orthocladiinae from southern Brazil
      (Diptera: Chironomidae).
AB  - A new species of Limnophyes Eaton collected in the Corvo Branco Mountains in
      Santa Catarina State is described and figured, based on male and female adults,
      larva and pupa. The species groups with L. griseata (Edwards) and L. bidumus
      Saether as the adults have a pronounced humeral pit with lanceolate setae and an
      additional group of lanceolate setae just posterior to antepronotum. The adults
      are, however, distinctly smaller, have a lower AR and have more lanceolate setae
      in the group just posterior to antepronotum than the two other species. The pupa
      can easily be separated from the pupa of L. bidumus as the anal macroseta is
      longer than the anal lobe. The larva lives hygropetric on vertical rock surfaces.
      A key to male adults of Neotropical Limnophyes is given. 

PMID- 25947769
TI  - Quisarctus yasumurai gen. et sp. nov. (Arthrotardigrada: Halechiniscidae) from a
      submarine cave, off Iejima, Ryukyu Islands, Japan.
AB  - Quisarctus yasumurai gen. et sp. nov. (Arthrotardigrada: Halechiniscidae) is
      described from the submarine cave 'Daidokutsu', off Iejima, Okinawa Islands,
      Ryukyu Islands, Japan. It is characterised by a cylindrical body, long primary
      clava and shorter lateral cirrus inserted on a common cirrophore, and simple
      digits of unequal lengths (without folds, peduncles, proximal pads, pretarsi, or
      wrinkles) that terminate in a sheathed, small, crescent-shaped claw with a minute
      calcar. Quisarctinae subfam. nov. is erected for this unique new genus. 

PMID- 25947770
TI  - Review of the family Anthogonidae (Diplopoda, Chordeumatida), with descriptions
      of three new species from the Balkan Peninsula.
AB  - Three new species of the family Anthogonidae are described from caves in Croatia
      and Montenegro, respectively: Egonpretneria vudutschajldi Antic & Drazina sp. n.,
      Haasia jalzici Antic & Drazina sp. n., and Macrochaetosoma bertiscea Antic &
      Makarov sp. n. All three subfamilies within Anthogonidae are diagnosed, with
      brief discussion of relationships between genera and notes on their biogeography.
      A map of the global distribution of Anthogonidae is presented, as well as maps of
      the distribution of each species of Balkan anthogonids, including numerous new
      locality data. The first SEM images are provided for some representatives of this
      family. A key is given to all seven anthogonid genera. The subfamily Haasiinae
      Hoffman, 1980 is a new synonym of Anthogonidae, syn. n., while Macrochaetosoma
      bifurcatum Curcic & Makarov, 2001 becomes a new synonym for M. troglomontanum
      Absolon & Lang, 1933, syn. n.. 

PMID- 25947771
TI  - Mayflies of the Caucasus Mountains. III. A new representative of the subgenus
      Rhodobaetis Jacob, 2003 (Baetidae: Baetis) from the South-Western Caucasus.
AB  - A new species of the subgenus Rhodobaetis Jacob, 2003, namely Baetis
      (Rhodobaetis) vadimi sp. nov., is described based on immature larvae from several
      localities in Georgia and Turkey. It is the ninth species of the subgenus for
      Transcaucasia, following six species formally recorded from Turkey and two
      endemic species described from the Central Caucasus. Larval characters are
      investigated and illustrated by means of scanning electron microscopy, and
      discussed in details. The differential diagnosis of this species is provided with
      regard to other representatives of the subgenus considering the feature set
      common for Rhodobaetis. The new species can be distinguished from its relatives
      (species which lack stout setae on the gills' margins), mainly by some characters
      of mouthparts (particularly labium), the shape and arrangement of stout setae and
      scales on the body surface, as well as the lack of subapical tiny setae on tarsal
      claw, and presence of numerous marginal spines and semilunar scale bases on the
      paraproct plate.

PMID- 25947772
TI  - On the taxonomic status of the Thai endemic freshwater snake Parahelicops
      boonsongi, with the erection of a new genus (Squamata: Natricidae).
AB  - Parahelicops boonsongi Taylor & Elbel, 1958 is known from only three specimens
      from Thailand. It has been placed either in the genus Parahelicops Bourret, 1934,
      along with Parahelicops annamensis Bourret, 1934, or in the genus Opisthotropis
      Gunther, 1872. We compared its morphological characters with those of P.
      annamensis and with three other relevant genera, Opisthotropis, Pararhabdophis
      Bourret, 1934, and Paratapinophis Angel, 1929. Parahelicops boonsongi is
      phenotypically distinct from Parahelicops annamensis, Opisthotropis, and all
      other natricine genera. We consequently erect a new genus, Isanophis gen. nov.,
      to accommodate Parahelicops boonsongi. 

PMID- 25947773
TI  - A new species of Hemigrammus Gill, 1858 (Characiformes: Characidae) from the
      central and western Amazon and rio Parana-Paraguai basins.
AB  - A new species of Hemigrammus is described from the middle rio Solimoes/Amazonas
      and tributaries, upper and middle rio Madeira, and rio Parana-Paraguai basins in
      Brazil and Paraguay. The new species is most similar among congeners with
      Hemigrammus marginatus, with which it shares similar caudal-fin pigmentation
      pattern. The new species can be distinguished from Hemigrammus marginatus by
      possessing two conspicuous dark patches of pigmentation on caudal fin, occupying
      most of caudal-fin lobes, except the tips, by having two dark narrow stripes
      along anal-fin base, and by possessing 5-8 pored lateral line scales. The new
      species differs from Hyphessobrycon diancistrus, which is similar in color
      pattern and general body shape, by the presence of small scales on caudal-fin
      lobes, occupying approximately its basal third, by the presence of two narrow
      stripes along anal fin base, and by the absence of bony hooks on analfin in
      mature males. The occurrence of the new species in both Amazon and rio Parana
      Paraguai basins is discussed in order to clarify and expand recent discussions on
      the biogeographical relationships between both river systems. 

PMID- 25947774
TI  - Description of Danio absconditus, new species, and redescription of Danio
      feegradei (Teleostei: Cyprinidae), from the Rakhine Yoma hotspot in south-western
      Myanmar.
AB  - Danio feegradei Hora is redescribed based on recently collected specimens from
      small coastal streams on the western slope of the Rakhine Yoma, ranging from the
      Thade River drainage southward to slightly north of Kyeintali. Danio absconditus,
      new species, is described from the Kyeintali Chaung and small coastal streams
      near Gwa, south of the range of D. feegradei. Both species are distinguished from
      other Danio by the presence of a dark, elongate or round spot at the base of the
      caudal fin and a cleithral marking composed of a small black spot margined by a
      much smaller orange spot. Danio feegradei is characterized by the colour pattern,
      with series of white spots along the otherwise dark side; D. absconditus by about
      7--11 dark vertical bars on the abdominal side. Within Danio, the presence of a
      complete lateral line, cleithral spot, and 14 circumpeduncular scales is shared
      with D. dangila and similar species, but these character states may be
      plesiomorphic as suggested by the shared presence of cleithral spot and complete
      lateral line in Devario and Betadevario. In other Danio the cleithral spot is
      absent, the lateral line is short or absent, and the circumpeduncular scale count
      is lower (10-12). Twenty teleost species are reported from streams on the western
      slope of the Rakhine Yoma, all probably endemic. The parapatric distribution of
      D. absconditus and D. feegradei is unique within the genus, and may be partly
      explained by changes in eustatic sea levels. 

PMID- 25947775
TI  - Melita mirzajanii n. sp. (Crustacea: Amphipoda: Melitidae), a puzzling new member
      of the Caspian fauna.
AB  - Described is Melita mirzajanii n. sp. (Melitidae) from the southwestern corner of
      the Caspian Sea. It shows no particular similarity to any species known from the
      Mediterranean Sea. It inhabits, as the only amphipod species, dense growths of
      Amphibalanus cf. improvisus (Darwin 1854) in a port, at low and highly
      fluctuating salinities. Its most striking characters are: absence of any pleonal
      or urosomal dorsal teeth (projections), elongated distal article of the
      mandibular palp, hind margin of last pereopod bases strongly narrowed distad, and
      epimera posterodistally rectangular. An identification key for the species group
      of Melita without dorsal teeth and without article 2 on the exopodite of the
      third uropod is provided. 

PMID- 25947776
TI  - Reassessment of multiple species of Gymnelus (Teleostei: Zoarcidae) in Pacific
      Arctic and boreal regions.
AB  - Recently described new nominal species and resurrected species in the eelpout
      genus Gymnelus Reinhardt 1834 were reassessed for validity using fresh material
      collected in Pacific Arctic regions and a large body of data from a previous
      systematic review of the genus. The analysis reported here included both DNA
      barcodes and morphology. Only two species were validated: G. viridis (Fabricius
      1780) and G. hemifasciatus Andriashev 1937. The latter species occurred as two
      morphotypes for which there is some evidence of difference in ecological
      preference, but the available environ-mental data are not robust enough to firmly
      identify or verify ecophenotypes. 

PMID- 25947777
TI  - Two tropical species of Stephanotheca (Bryozoa, Cheilostomata, Lanceoporidae)
      from the Gulf of Carpentaria, Australia.
AB  - Two new species of Stephanotheca are described from the southeast Gulf of
      Carpentaria, northern Australia, providing the first tropical records of this
      genus. Stephanotheca ipsum n. sp. is provisionally placed in the genus on the
      basis of a low ridge of calcification around the edge of the ooecium, which
      differs from the fully pseudoporous ooecium of Calyptotheca (Lanceoporidae) and
      resembles the 'crowned' ooecium of Stephanotheca, with a central porous area
      surrounded by a nodular imperforate area. Stephanotheca ipsum and Stephanotheca
      romajoyae n. sp. are the only species in the genus with more than one avicularium
      on some zooids. The latter species is distinguished by high variability in
      avicularium size, shape, position and orientation; it also shares dimorphic
      avicularia with S. ochracea (Hincks) and is the only species in which they
      sometimes occur together on the same zooid. This study increases the number of
      Australian Stephanotheca species to four. The Australian species all have smaller
      primary orifices and variations in ovicell morphology compared with other, all
      European, species. In S. ipsum n. sp. the ooecia are ridged, those of S.
      victoriensis Reverter-Gil et al. have a single row of pseudopores forming an
      arch, and those of S. ambita (Waters) and S. romajoyae n. sp. have a relatively
      large pseudoporous area and smaller, lower nodular imperforate area. None of the
      Australian species have vicarious avicularia, which are known only from the type
      species, S. barrosoi Reverter-Gil et al. 

PMID- 25947778
TI  - Paraneseuthia Franz in the Indian Himalayan Region and Western Palaearctic
      (Coleoptera, Staphylinidae, Scydmaeninae).
AB  - Paraneseuthia loebli sp. n. (northern India) and P. meybohmi sp. n. (central
      southern Turkey) are described. This is the first record of Paraneseuthia west of
      Sundaland, with the Turkish species occurring over seven thousand kilometers
      westward from the hitherto known westernmost range of this genus. Moreover, for
      the first time Paraneseuthia is reported to occur in the Mediterranean zone of
      moderate climate. Previously proposed phylogeographic hypotheses concerning the
      evolution of Paraneseuthia are discussed and the currently known distribution of
      this genus is summarized. 

PMID- 25947779
TI  - A new cicada species of the genus Psithyristria Stal, 1870 (Hemiptera: Cicadidae:
      Cicadinae: Psithyristriini) from Luzon, Philippines, with a key to the 15
      species.
AB  - A new species of the genus Psithyristria Stal, 1870, Psithyristria ridibunda sp.
      nov., is described from Quezon, Luzon, Philippines. The new species is very
      similar to Psithyristria incredibilis Lee & Hill, 2010, but the cubital cell is
      distinctly larger than the radial cell and the medial branch of the uncal lobe is
      much shorter than the lateral branch and has two tiny apical spines.
      Psithyristria isarogensis Boulard & Yap, 2013 is synonymized with Psithyristria
      paracrassis Lee, 2010. A revised key to the 15 species of Psithyristria is
      provided. 

PMID- 25947780
TI  - A redescription of Yoyetta landsboroughi (Distant) and Y. tristrigata (Goding and
      Froggatt) (Hemiptera: Cicadidae) and description of four new related species.
AB  - This study provides redescriptions of two small cicada species, Yoyetta
      landsboroughi (Distant) and Y. tristrigata (Goding and Froggatt), from eastern
      Australia, based on a detailed morphological examination of available material.
      The status of Y. toowoombae (Distant) is re-examined and it is now formally
      recognised to be a junior synonym of Y. landsboroughi. Four new species of
      Yoyetta are described, also from eastern Australia. These are: Y. cumberlandi sp.
      nov., Y. fluviatilis sp. nov., Y. nigrimontana sp. nov., and Y. repetens sp.
      nov.. Within each species (re)description, sections on distinguishing features,
      distribution, habitat and behaviour, and calling song structures are described
      and illustrated where appropriate. 

PMID- 25947781
TI  - Tanaidaceans from Brunei, V. The Leptocheliidae (Crustacea: Peracarida:
      Tanaidacea), with four new species.
AB  - Leptocheliid material from sublittoral sandy substrata in the South China Sea off
      the coast of Brunei has been analyzed. Four species, all new to science, are
      described, all apparently interstitial in habitat. One is the second species to
      be described in the genus Catenarius (C. magdae); the others represent three new
      genera, one in each of the subfamilies Konariinae (Brunarus colekanus),
      Catenariinae (Ektraleptochelia phoxops) and Leptocheliinae (Nuberis
      areolaticola). As a result of the new information on the morphology of
      catenariins, the Andaman Sea species Leptochelia elongata is transferred to a new
      genus (Larsmentia) in the Catenariinae. 

PMID- 25947782
TI  - Ptenidium pusillum (Gyllenhal, 1808) from egg to pupa (Coleoptera: Ptiliidae).
AB  - Eggs, larvae and pupae of Ptenidium pusillum obtained by rearing adults are
      described. Larval chaetotaxy is treated in detail. Two larval instars are
      identified, differing in minor chaetotaxic characters, pigmentation and
      measurements. The lack of urogomphi, confirmed in Ptenidium, is discussed in the
      context of current systematics of Ptiliidae. Serial chaetotaxic homology and
      between-instar homology are discussed. Observations related to biology of P.
      pusillum and associations with phoretic mites and nematodes are given. 

PMID- 25947783
TI  - The presence of Notanisus Walker (Hymenoptera: Pteromalidae) in North America and
      revision of the oulmesiensis species group.
AB  - The presence and distribution of two species of Notanisus Walker (Hymenoptera:
      Pteromalidae) in North America is reported. Notanisus sexramosus (Erdos),
      originally described from Hungary and previously reported from Maryland, USA, is
      recorded also from Massachusetts and Pennsylvania based on a male and
      macropterous and brachypterous females. Males of Notanisus are shown to have two
      types of flagellar structure, ramose and pedicellate, and diagnostic features are
      given for the previously unknown males of N. clavatus Boucek to differentiate
      these from those of N. sexramosus and N. versicolor Walker. Five other species
      are newly described, Notanisus kansensis n. sp. based on a female from Nebraska,
      USA, and four species from Sub-Saharan Africa and the Arabian Peninsula-
      Notanisus brevipetiolus n. sp. based on two females from Uganda and Zambia,
      Notanisus longipetiolus n. sp. based on a female from Zimbabwe and a female and
      two males from Mozambique, Notanisus vanharteni n. sp. based on a female and
      several males from United Arab Emirates, and Notanisus yemenensis n. sp. based on
      a female and male from Yemen. The latter five species are included with the
      Palaearctic species N. oulmesiensis (Delucchi) and N. gracilis (Yang) in the
      oulmesiensis species group, defined by the presence of reduced stigmal and
      postmarginal veins in both sexes. The seven oulmesiensis-group species are
      differentiated in a key and all treated species are illustrated through
      macrophotography. Monophyly and relationships of Notanisus within Cleonymini are
      discussed, including features that indicate it could be paraphyletic relative to
      Callocleonymus Masi.

PMID- 25947784
TI  - Phalangopsidae crickets from Tropical Africa (Orthoptera, Grylloidea), with
      descriptions of new taxa and an identification key for African genera.
AB  - New Phalangopsidae crickets are described from tropical Africa, including three
      new genera and ten new species: Afrophaloria Desutter-Grandcolas, n.gen.,
      Afrophaloria amani Desutter-Grandcolas, n. sp., type species, Afrophaloria
      apiariensis Desutter-Grandcolas, n. sp., Afrophaloria hempae Desutter-Grandcolas,
      n. sp., Kameruloria gabonensis Desutter-Grandcolas, n. sp., Kameruloria
      nigricornis Desutter-Grandcolas, n. sp., Kameruloria trimaculata Desutter
      Grandcolas, n. sp., Paragryllodes amani Desutter-Grandcolas, n. sp.,
      Phasmagryllus Desutter-Grandcolas, n.gen., Phasmagryllus elegans Desutter
      Grandcolas, n. sp., type species, Upupagryllus Desutter-Grandcolas, n.gen.,
      Upupagryllus subalatus Desutter-Grandcolas, n. sp., type species, and
      Upupagryllus alatus Desutter-Grandcolas, n. sp. All these taxa, except
      Paragryllodes amani Desutter-Grandcolas, n. sp., belong to the subfamily
      Phaloriinae. The subfamily is redefined, to take into account their morphological
      (apterous taxa) and ecological (straminicolous taxa) diversity. A key for
      phalangopsid African genera is proposed, and the status of Larandeicus Chopard,
      1937 briefly discussed. 

PMID- 25947786
TI  - Redescription of the eagle rays Myliobatis hamlyni Ogilby, 1911 and M. tobijei
      Bleeker, 1854 (Myliobatiformes: Myliobatidae) from the East Indo-West Pacific.
AB  - The eagle rays Myliobatis hamlyni Ogilby, 1911 and Myliobatis tobijei Bleeker,
      1854 are redescribed based on museum specimens and new material from Australia,
      Indonesia, the Philippines, Taiwan and Japan. These two species are closely
      related to Myliobatis aquila (L.) from the eastern Atlantic and can be
      distinguished from each other by a combination of their coloration, meristics,
      depth preferences and subtle morphometric characters. Myliobatis hamlyni was
      previously considered to be an Australian endemic, but its distribution is herein
      extended northward to Taiwan and Okinawa. Myliobatis tobijei was considered to
      occur southwards from Japan to Indonesia, but its distribution is herein
      restricted to the western North Pacific, primarily Japan. 

PMID- 25947785
TI  - Revision of the Palaearctic brood parasitic genus Nipponodipogon Ishikawa, 1965
      of spider wasps (Hymenoptera: Pompilidae: Pepsinae).
AB  - The systematics and bionomics of the Palaearctic brood parasitic genus
      Nipponodipogon Ishikawa, 1965 are revised. Seven species are listed. A new
      species N. sudai Shimizu, sp. nov. (Japan, Honshu) and the hitherto unknown males
      of N. iwatai (Ishikawa, 1965) and N. nagasei (Ishikawa, 1965) are described and
      illustrated. Six species from Japan and the Russian Far East are redescribed. A
      key to species is provided. 

PMID- 25947787
TI  - Description of free-living marine nematodes found in the intestine of fishes from
      the Brazilian coast.
AB  - The marine nematodes usually comprise free-living species, although a few are
      parasitic. However, several cases of free-living nematodes found accidentally in
      the digestive tract of certain vertebrates, especially fishes, have sometimes
      been recorded and categorized as pseudoparasites. In the present work, two
      species of marine fishes, the rhomboid crappie, Diapterus rhombeus, and the
      silvered crappie, Eucinostomus argenteus (Perciformes: Gerreidae), from Angra dos
      Reis on the coast of Rio de Janeiro (Brazil) were examined. Seven species of free
      living marine nematodes were found in the digestive tract of these fish. Several
      of these species remain unknown as free-living forms in Brazil. The combination
      of the fish feeding strategies and the poor preservation of the body of the
      nematode specimens found could indicate that these nematodes are pseudoparasites,
      appearing in the fishes' digestive tracts through accidental ingestion and
      thereafter surviving for brief periods of time. Descriptions, illustrations and
      tables of measurements are provided for all species. Six of these species
      (Croconema torquens, Dorylaimopsis pellucida, Oncholaimellus labiatus,
      Parodontophora breviamphida, Prooncholaimus ornatus, Trissonchulus latus) have
      been reported for the first time from the Brazilian coast. 

PMID- 25947788
TI  - Description of three new species of Labena Cresson from Mexico (Hymenoptera,
      Ichneumonidae, Labeninae), with notes on tropical species richness.
AB  - Three new species of Labena Cresson (Ichneumonidae, Labeninae); L. littoralis sp.
      nov., L. tekalina sp. nov. and L. madoricola sp. nov. are described and
      illustrated. Material was collected with Malaise traps in 2008 and 2009 in the
      Biosphere Reserve Ria Lagartos (Mexico). Diagnostic characters to distinguish
      them from all other New World species of the genus are provided. In addition, the
      tropical species richness of the genus is shortly discussed. 

PMID- 25947789
TI  - First record of Mollisquama sp. (Chondrichthyes: Squaliformes: Dalatiidae) from
      the Gulf of Mexico, with a morphological comparison to the holotype description
      of Mollisquama parini Dolganov.
AB  - The description of the pocket shark genus Mollisquama (M. parini Dolganov, 1984)
      is based on a single known specimen collected from the Nazca Ridge of the
      southeast Pacific Ocean. A second Mollisquama specimen has been captured in the
      central Gulf of Mexico establishing a considerable range extension and a
      parturition locality because the specimen has a healed vitelline scar. Both the
      holotype of M. parini and the Gulf of Mexico specimen possess the remarkable
      pocket gland with its large slit-like external opening located just above the
      pectoral fin. Features found on the Gulf of Mexico specimen that were not noted
      in the description of M. parini include a series of ventral abdominal photophore
      agglomerations and a modified dermal denticle surrounded by a radiating
      arrangement of denticles just posterior to the mouth. Based on a morphometric and
      meristic comparison of the Gulf of Mexico specimen with information in the
      description of M. parini, the Gulf of Mexico specimen is identified as
      Mollisquama sp. due to differences in tooth morphology and vertebral counts.
      Phylogenetic analysis of NADH2 gene sequences places Mollisquama sister to
      Dalatias plus Isistius within the family Dalatiidae. 

PMID- 25947790
TI  - A review of Billaea Robineau-Desvoidy of the eastern Palearctic and Oriental
      regions (Diptera: Tachinidae).
AB  - The species of Billaea Robineau-Desvoidy (Diptera, Tachinidae) from the eastern
      Palearctic and Oriental regions are revised. Ten described species are
      recognized, viz. B. atkinsoni (Baranov) (new records for Japan, Laos, Malaysia,
      Pakistan and Thailand), B. ficorum (Townsend), B. fortis (Rondani), B. impigra
      Kolomiets (new record for China), B. kolomyetzi Mesnil, B. malayana Malloch, B.
      morosa Mesnil, B. robusta Malloch, B. steini (Brauer et Bergenstamm) and B.
      triangulifera (Zetterstedt) and nine species are described as new to science, B.
      brevicauda Zhang et Shima sp. nov. (China), B. carinata Zhang et Shima sp. nov.
      (China), B. chinensis Zhang et Shima sp. nov. (China and Vietnam), B. flava Zhang
      et Wang sp. nov. (China), B. kurahashii Zhang et Shima sp. nov. (Laos and
      Thailand), B. micronychia Zhang et Shima sp. nov. (China and Japan; previously
      misidentified from China as B. irrorata (Meigen)), B. papei Zhang et Shima sp.
      nov. (Malaysia), B. setigera Zhang et Shima sp. nov. (China) and B. verticalis
      Shima et Zhang sp. nov. (China). Billaea fasciata (Townsend, 1928) is treated as
      a junior synonym of B. ficorum (Townsend, 1916), syn. nov. Billaea irrorata is no
      longer recorded from the eastern Palearctic. A key to 19 species of Billaea from
      the eastern Palearctic and Oriental regions and 101 figures of male terminalia,
      bodies, heads and abdomens are given.

PMID- 25947791
TI  - Phylogenetic relationships of the species and biogeography of the characid genus
      Oligosarcus Gunther, 1864 (Ostariophysi, Characiformes, Characidae).
AB  - The characid genus Oligosarcus consists of 20 described species distributed
      throughout most of South American river basins below 14o south latitude. This
      study focus on the phylogenetic relationships of the species of Oligosarcus based
      on the analysis of osteological characters to provide data to discuss the
      biogeographic history of the genus. The analysis resulted in a single most
      parsimonious tree with 152 steps (CI= 0.355 and RI= 0.600). The 18 included
      Oligosarcus species were hierarchically organized into 17 clades. A minimal age
      of 15 Ma for the genus is suggested based on the putatively cladogenetic event
      represented by the continued shortening of the Eastern Cordillera that
      established the eastern boundary of the modern central Andean plateau and was
      responsible for cladogenesis between the common ancestor of O. schindleri + O.
      bolivianus versus the remaining congeners. There is a pronounced disjunction in
      the upland species distribution by the lowland areas of the Chaco-Pantanal basin.
      This indicates that upland habitats (headwater streams) are preferential habitats
      for a set of species including O. argenteus, O. bolivianus, O. brevioris, O.
      paranensis, O. perdido, O. pintoi, O. planaltinae, O. brevioris, and O.
      schindleri. Fragmentation of populations of O. pintoi and O. perdido are at least
      2.5 Ma old, since the origin of the upper Paraguay depression clearly promoted
      the present-day observed disjunction in the distribution of these species. The
      lowland Oligosarcus species are all included in a single clade but the obtained
      results suggest that fragmentation of upland versus lowland components of the
      genus was not causally related to a single vicariant event. The available fossil
      record of Oligosarcus indicates that the genus already occurred in the coastal
      plain at about 2.3 to 1.25 Ma. The sister-group relationship between O. hepsetus
      and O. longirostris provided additional evidences of the so-called historical
      affinities between the SE Brazilian coastal plain and the Rio Iguacu drainage
      basin. 

PMID- 25947792
TI  - The genus Ontherus Erichson 1847 (Coleoptera: Scarabaeidae: Scarabaeinae):
      description of a new species, and notes on the genus in Colombia.
AB  - The state of knowledge of the genus Ontherus Erichson 1847 in Colombia is
      reviewed and updated since the revision of the genus by Genier (1996), and the
      species list for Colombia of Medina et al. (2001). Two new distributional records
      for Colombia are confirmed; Ontherus politus Genier 1996 and Ontherus gilli
      Genier 1996. An updated species list of Ontherus for Colombia is presented with
      comments on the species with doubtful distribution in Colombia. O. felicitae n.
      sp., a new species from the mexicanus species group, is described from Western
      Andes of Colombia. 

PMID- 25947793
TI  - Three new species of the Eriopisa group (Crustacea: Amphipoda: Eriopisidae) from
      Japan, with the description of a new genus.
AB  - Three new species of the Eriopisa group (Crustacea: Amphipoda: Eriopisidae) are
      described from coastal areas in Japan. Paraflagitopisa gen. nov. is established
      with P. excavata sp. nov. as its type species. This new genus is characterized by
      (1) entire lateral cephalic lobe, (2) unfused flagellum of antenna 2, (3) 3
      articulated mandibular palp, (4) carpus of gnathopod 1 longer than propodus, (5)
      transverse palm of gnathopod 1, and (6) slender outer ramus of uropod 3 with long
      second article, and can be distinguished from the closely related genus,
      Flagitopisa, by the article 2 of mandibular palp longer than article 3, the
      undilated bases of pereopods 3-4, and the slender inner ramus of uropod 3.
      Psammogammarus lobatus sp. nov. is characterized by (1) male gnathopod 2 with
      excavated palm, (2) posterodistally projected bases of pereopods 5-7, (3)
      quadrate posteroventral corner of pleonal epimeron 3, (4) short inner ramus of
      uropod 3, and (5) article 2 of uropod 3 outer ramus longer than article 1.
      Victoriopisa wadai sp. nov. has the following characters: (1) eyes absent, (2)
      peduncle of antenna 1 not heavily setose, (3) accessory flagellum with 1-2
      articles, (4) flagellum of antenna 2 composed of 2 long and 3 short articles, (5)
      gnathopod 2 in both sexes with excavated palm, (6) merus of pereopod 7 moderately
      expanded, and (7) ventral margin of pleonite 2 slightly setose. Key to species of
      the Eriopisa group in Japan is provided. 

PMID- 25947794
TI  - Revision of Heringina Aczel, 1940 (Diptera: Tephritidae), with description of a
      new species from Iran and Turkey.
AB  - The genus Heringina Aczel, 1940 is revised and shown to belong to the Tephritis
      group of genera and is closely related to Tephritis and Multireticula. Literature
      records are revised, and available collection material is listed. The genus
      includes two species: H. guttata (Fallen 1814) originally described from the sand
      dunes of southern Sweden and occurring from the Baltic region through Ukraine and
      Caucasus to Turkey, Iran, Kazakhstan, and Kyrgyzstan, and Heringina arezoana sp.
      nov., found in Iran and eastern Turkey. Both species are described, illustrated,
      and keyed. Host plants and localization of larvae remain unknown; adult flies of
      both species are commonly swept from (but never reared) flower heads of
      Helichrysum arenarium. Other records of host plants listed by Boie (1847) and
      repeated in most important European monographs, are obviously based on
      misidentified flies. Possible relationships of Heringina with Tephritis and
      Multireticula are discussed. 

PMID- 25947795
TI  - Pseudonannolene lundi n. sp., a new troglobitic millipede from a Brazilian
      limestone cave (Spirostreptida: Pseudonannolenidae).
AB  - Pseudonannolene lundi n. sp., is described from Lapa Sem Fim Cave, a limestone
      cave from Luislandia municipality, Minas Gerais State, Brazil. The species is the
      eighth troglobitic millipede and the third of the genus Pseudonannolene described
      from Brazilian caves. Pseudonannolene lundi shows pronounced depigmentation and
      decrease of body size, as found in other troglobitic species belonging to the
      genus. The gonopod has a robust and evident internal branch, and a solenomere
      slightly trianguliform. 

PMID- 25947796
TI  - A new species of Magnimyiolia Shiraki (Diptera: Tephritidae: Trypetinae) and new
      records of Acanthonevrini from India.
AB  - A new species of the subfamily Trypetinae, Magnimyiolia perennifascia Singh &
      David, sp. nov. (Trypetini) is described from India. Two species of subfamily
      Phytalmiinae, Ectopomyia baculigera Hardy and Ptilona conformis Zia
      (Acanthonevrini) are recorded for the first time from India. An updated key to
      Oriental species of Magnimyiolia Shiraki is provided. 

PMID- 25947797
TI  - Two new species of the genus Sorolopha Lower (Lepidoptera: Tortricidae) from
      northern Thailand.
AB  - Two new species of Sorolopha Lower (i.e., S. suthepensis, n. sp., and S. undula,
      n. sp.) are described and illustrated from male specimens collected in
      agricultural areas and natural forest in Doi Suthep-Pui National Park, Chiang Mai
      Province, Thailand. 

PMID- 25947798
TI  - First report of Toumeyella parvicornis (Cockerell) in Europe (Hemiptera:
      Coccidae).

PMID- 25947799
TI  - A review of Trachusoides Michener and Griswold (Hymenoptera: Megachilidae).
AB  - The rare genus Trachusoides, previously known only from a single species
      inhabiting the Western Ghats of India, is reviewed. Trachusoides elsieae, new
      species, is described from Laos, additional records for T. simplex are
      documented, and a key to separate the species is provided. 

PMID- 25947800
TI  - Revision of the genus Aulacophora from Taiwan (Coleoptera: Chrysomelidae:
      Galerucinae).
AB  - Ten species of the genus Aulacophora Chevrolat, 1836 are reported for Taiwan.
      Specimens of A. opacipennis Chujo, 1962 collected from Southeast Asia were
      misidentified by Kimoto (1989) and should be identified as A. apicipes Jacoby,
      1896. Color photos of habitus and drawings of male and female genitalia from
      eleven species (including A. apicipes) are presented. The following synonymies
      are proposed: Aulacophora analis (Weber, 1801) = Galeruca quadraria Olivier, 1808
      (syn nov.); A. indica (Gmelin, 1790) = Rhaphidopalpa pubescens Allard, 1888 (syn.
      nov.); A. apicipes Jacoby, 1896 = A. nigripalpis Chen and Kung, 1959 (syn nov.).
      Lectotypes are designated for Crioceris abdominalis Fabricius, 1781, C. testacea
      Fabricius, 1787, Galleruca bicolor Weber, 1801, Galeruca quadraria Olivier, 1808,
      Aulacophora semiopaca Jacoby, 1886, A. frontalis Baly, 1888, A. lewisii Baly,
      1886, A. intermedia Jacoby, 1892, A. semifusca Jacoby, 1892, A. dohrni Jacoby,
      1899, A. almora Maulik, 1936, A. apicipes Jacoby, 1896, A. tenuicincta Jacoby,
      1897, Rhaphidopalpa pubescens Allard, 1888, R. bengalensis Weise, 1892, R.
      ceramensis Weise, 1892, R. chinensis Weise, 1892, and Orthaulaca (Ceratia)
      cattigarensis Weise, 1892. A key to the Taiwanese species is provided. 

PMID- 25947801
TI  - Establishment of Oulenziella gen. nov. for Oulenzia bakeri (Hughes, 1962) (Acari:
      Winterschmidtiidae).
AB  - A new genus, Oulenziella, is proposed for Oulenzia bakeri (Hughes, 1962), a
      species originally collected on jute (Corchorus sp., Malvaceae) from India.
      Oulenziella bakeri (Hughes, 1962) comb. nov. is re-described. Oulenzia gossypii
      Meyer & Rodrigues, 1965 collected from Gossypium sp. in Mozambique is considered
      a junior synonym of Oulenziella bakeri. The new genus differs from Oulenzia in
      having hT present on tibiae I and II, kT on tibia IV, la and ra on tarsus II, w
      and r on tarsus III, e and f on tarsi I-III; and by seta d on tarsi III and IV
      positioned at level of apical 1/8 to 1/6 of the segments. 

PMID- 25947802
TI  - Association of immature stages of some caddisfly species from northwestern
      Argentina with description of a new species of Helicopsyche (Trichoptera:
      Helicopsychidae).
AB  - The adult, larva, and pupa of Helicopsyche obscura sp. nov. from northwestern
      Argentina are described and illustrated. Descriptions and illustrations of adults
      and associated pupae and larvae of Helicopsyche turbida Navas and Leptonema
      boliviense boliviense Mosely are included. The associations of immature stages
      were made using the metamorphotype method. Helicopsyche turbida is newly recorded
      from Tucuman province. The adult males of H. obscura sp. nov. and H. turbida have
      similar structure in the genital segments, however, the most clear differences
      are in the general color and size of the adult, and in the color, size, and
      morphology of the metanota in the larval stages as well as the shapes of
      mandibles, hook plates, and terminal segments of the pupal stages. The larva and
      pupa of L. boliviense boliviense are compared with those of L. columbianum and
      other previously described species, providing differences in color, chaetotaxy,
      and morphology. 

PMID- 25947804
TI  - Description of the female of Cordulegaster vanbrinkae (Lohmann, 1993) (Odonata:
      Anisoptera: Cordulegastridae).
AB  - The female of Cordulegaster vanbrinkae is described and illustrated, basing on
      four specimens collected in Gilan and Mazandaran Provinces, northern Iran. Their
      characters and variability are shown and compared with females of other
      Cordulegaster species. 

PMID- 25947803
TI  - Morphological and morphometric comparison of the first zoeal stage of the
      mangrove crabs of the genus Aratus H. Milne Edwards, 1853 (Decapoda: Sesarmidae).
AB  - The mangrove crab Aratus pisonii (H. Mile Edwards, 1837) was considered to have
      an amphi-American distribution but a recent genetic study revealed that the
      Eastern Tropical Pacific populations represent a new species, A. pacificus
      (Thiercelin & Schubart, 2014). These sister species separated by the Central
      American Isthmus have developed under different environmental conditions that may
      influence their larval development. A comparison of morphological and
      morphometric features (length and width of cephalothorax and length of rostral
      and dorsal spine, antenna, antennule, telson, and furcae) of recently-hatched
      larvae of A. pacificus (Pacific coast) and A. pisonii (Caribbean coast) from
      Costa Rica revealed that the setation pattern of the antennules differed between
      the species and the analyzed morphometric features were larger in A. pisonii
      larvae. Difference in size may be a response to different environmental
      conditions, as the lower primary production in coastal Caribbean waters, which
      may have forced females of A. pisonii to allocate more energy into the offspring,
      resulting in larger zoeal size. A greater endogenous reserve may allow the larvae
      to reduce the duration of the planktonic phase and increase the size at
      metamorphosis, thus enhancing their survival chances during the planktonic phase.
      These data regarding morphological and morphometric differences in recently
      hatched larvae of the Pacific and Caribbean species support the conclusion that
      specimens of Aratus from both coasts of Costa Rica represent indeed different
      species. 

PMID- 25947805
TI  - Collembola of Rapa Nui (Easter Island) with descriptions of five endemic cave
      restricted species.
AB  - Eight species of Collembola are reported from recent collections made in caves on
      the Polynesian island of Rapa Nui (Easter Island). Five of these species are new
      to science and apparently endemic to the island: Coecobrya aitorererere n. sp.,
      Cyphoderus manuneru n. sp., Entomobrya manuhoko n. sp., Pseudosinella hahoteana
      n. sp. and Seira manukio n. sp. The Hawaiian species Lepidocyrtus olena
      Christiansen & Bellinger and the cosmopolitan species Folsomia candida Willem
      also were collected from one or more caves. Coecobrya kennethi Jordana & Baquero,
      recently described from Rapa Nui and identified as endemic, was collected in
      sympatric association with C. aitorererere n.sp. With the exception of F.
      candida, all species are endemic to Rapa Nui or greater Polynesia and appear to
      be restricted to the cave environment on Rapa Nui. A key is provided to separate
      Collembola species reported from Rapa Nui. We provide recommendations to aid in
      the conservation and management of these new Collembola, as well as the other
      presumed cave-restricted arthropods. 

PMID- 25947806
TI  - Three new species of genus Sinophorus Forster (Hymenoptera, Ichneumonidae)
      parasitizing twig and defoliating Lepidoptera.
AB  - Three new wasp species are described from the subfamily Campopleginae
      (Hymenoptera: Ichneumonidae), Sinophorus bazariae Sheng, sp. n., reared from
      Bazaria turensis Ragonot (Lepidoptera, Pyralidae) in Dulan County, Qinghai
      Province, China, S. nigrus Sheng, sp. n., reared from Epinotia rubiginosana
      rubiginosana (Herrich-Schaffer) (Lepidoptera, Tortricidae) in Weichang, Hebei
      Province, and S. zeirapherae Sheng, sp. n., reared from Zeiraphera grisecana
      (Hubner) (Lepidoptera, Tortricidae) in Liupanshan, Ningxia Hui Autonomous Region.
      A key to the species of Chinese Sinophorus is provided. 

PMID- 25947807
TI  - New mayfly genera from the Middle Triassic of Poland and their evolutionary and
      paleogeographic implications (Ephemerida: Litophlebiidae, Vogesonymphidae).
AB  - Two new mayfly genera and species from the Triassic deposits of the Palegi area
      (southeast Poland) are described. This is the first description of aquatic
      insects from the Palegi locality. Triassolitophlebia palegica gen. et sp. nov.
      (Litophlebiidae) is established on the basis of an isolated forewing. This is the
      first finding of this family in the Northern Hemisphere, known previously only
      from the Molteno Formation (South Africa). This is also the first mayfly family
      from the Triassic which has been found in both Hemispheres, providing additional
      evidence of the presumed similarity of aquatic insect faunas in the Southern and
      Northern Hemispheres during the Triassic. The consistent wing venation of ancient
      mayflies with homonomous wings could be evidence that they originated from the
      same ancestor. The second new mayfly, Palegonympha triassica gen. et sp. nov.
      (Vogesonymphidae), is described on the basis of a single fossil nymph (imprint of
      the exuviae) and indicates the similarity of the Palegi arthropod assemblage to
      that described from the Middle Triassic of France. The presence of a mayfly nymph
      in the last instar stage suggests not only that the Palegi deposit represents a
      fluvial environment with well-oxygenated and limpid water but also that these
      conditions lasted long enough to allow for such development. 

PMID- 25947808
TI  - Rivulus berovidesi, a new killifish species (Teleostei: Rivulidae) from western
      Cuba.
AB  - Rivulus berovidesi, a new killifish species, is described from a small stream in
      Sierra de Cajalbana, northwestern Cuba. It is readily distinguished from Rivulus
      cylindraceus Poey by the combination of an exclusive color pattern and meristic
      characters such as a d-type frontal scalation pattern (versus e-type pattern in
      Rivulus cylindraceus). The current diagnosis of Rivulus berovidesi based on
      chromatic, morphological and meristic characters is consistent with a recent
      molecular analysis of this genus in Cuba. 

PMID- 25947809
TI  - A new species of Acroleptus Bourgeois (Coleoptera: Lycidae) from the Brazilian
      Amazonian rainforest, with a note on its homonymy with Acroleptus Cabanis (Aves).
AB  - Acroleptus costae sp. nov. is described from the Brazilian Amazonian rainforest,
      raising the diversity of the formerly monotypic genus to two known species. The
      validity of Acroleptus Bourgeois, 1886 (Insecta) is maintained while Acroleptus
      Cabanis, 1861 (Aves) is considered to be an incorrect subsequent spelling. 

PMID- 25947810
TI  - How to inventory tropical flies (Diptera)--One of the megadiverse orders of
      insects.
AB  - A new approach to inventory Diptera species in tropical habitats is described. A
      150 x 266 m patch of cloud forest at Zurqui de Moravia, Costa Rica (10.047N,
      84.008W) at 1585 meters asl was sampled with two Malaise traps for slightly more
      than one year (Sept. 12, 2012-Oct. 18, 2013). Further concomitant sampling with a
      variety of trapping methods for three days every month and collecting during a
      one-week intensive "Diptera Blitz", with 19 collaborators collecting on-site,
      provided diverse additional samples used in the inventory. Two other Costa Rican
      sites at Tapanti National Park (9.720N, 83.774W, 1600 m) and Las Alturas (8.951N,
      82.834W, 1540 m), 40 and 180 km southeast from Zurqui de Moravia, respectively,
      were each sampled with a single Malaise trap to allow for beta-diversity
      assessments. Tapanti National Park was sampled from Oct. 28, 2012-Oct. 13, 2013
      and Las Alturas from Oct. 13, 2012-Oct. 13, 2013. A worldwide group of 54 expert
      systematists are identifying to species level all 72 dipteran families present in
      the trap samples. Five local technicians sampled and prepared material to the
      highest curatorial standards, ensuring that collaborator efforts were focused on
      species identification. This project, currently in its final, third year of
      operation (to end Sept. 1, 2015), has already recorded 2,348 species and with
      many more yet expected. Unlike previous All Taxon Biodiversity Inventories, this
      project has attainable goals and will provide the first complete estimate of
      species richness for one of the four megadiverse insect orders in a tropical
      region. Considering that this is the first complete survey of one of the largest
      orders of insects within any tropical region of the planet, there is clearly
      great need for a consistent and feasible protocol for sampling the smaller but
      markedly more diverse smaller insects in such ecosystems. By weight of their
      species diversity and remarkable divergence of habit, the Diptera are an
      excellent model to gauge microhabitat diversity within such systems. Our model
      appears to be the first to provide a protocol that can realistically be expected
      to provide a portrayal of the true species diversity of a megadiverse order of
      insects in the tropics.

PMID- 25947811
TI  - Additional records of the genus Colletes Latreille (Hymenoptera: Apoidea:
      Colletidae) from Siberia, with a checklist of Russian species.
AB  - In addition to a previously published study about Siberian Colletes species, we
      here further report on poorly known species. Twenty six species are currently
      known from Siberia with C. cinerascens Morawitz 1893, C. kaszabi Kuhlmann 2002,
      and C. ebmeri Kuhlmann 2002 found in Russia for the first time and C. wacki
      Kuhlmann 2002 is newly recorded from the Asian part of Russia. The male of C.
      wacki is here described for the first time and a lectotype designated for the
      closely related C. conradti Noskiewicz 1936 to clarify the taxonomy of this
      group. Colletes uralensis Noskiewicz 1936 was erroneously recorded from Russia
      and is removed from the list of Russian species. Images and updated distribution
      maps are provided for the closely related C. kaszabi and C. uralensis as well as
      for C. conradti and C. wacki to facilitate their identification. An updated
      checklist of the 42 species of Colletes so far known from Russia is provided. 

PMID- 25947812
TI  - Onuphis and Aponuphis (Annelida: Onuphidae) from southwestern Europe, with the
      description of a new species.
AB  - This study recognises five species of Onuphis and four species of Aponuphis from
      southwestern Europe, represented in the Bay of Biscay, the Atlantic coasts of
      Iberia and the western Mediterranean Sea. One species, Onuphis anadonae sp. nov.,
      is newly described and another species, Aponuphis willsiei Cantone & Bellan, 1996
      is a new record for the Iberian Peninsula waters. Aponuphis ornata (Fauvel, 1928)
      and A. willsiei are shown to be tube brooders and the development of the
      juveniles is described. The usefulness of some Onuphis characters, as well as the
      size-dependent distribution of branchiae and chaetae, complicating Aponuphis
      species identification, are discussed. We are presenting descriptions and
      photographs of the distinctive Aponuphis colour pattern which we recommend as an
      identificatory tool instead. A dichotomous key to all species is included. 

PMID- 25947813
TI  - The lacteus-, laspeyresiella- and mycetophilus-groups of Apanteles Foerster, 1862
      (Hymenoptera, Braconidae, Microgastrinae) in China, with descriptions of eight
      new species.
AB  - The lacteus-, mycetophilus- and laspeyresiella-groups of the genus Apanteles
      Foerster (Hymenoptera, Braconidae, Microgastrinae) are newly recorded from China
      with eight new species being described, namely A. basicavus Liu & Chen, sp. n. of
      the lacteus-group; A. brevivena Liu & Chen, sp. n. and A. parapholetesor Liu &
      Chen, sp. n. of the mycetophilus-group; A. artustigma Liu & Chen, sp. n., A.
      hainanensis Liu & Chen, sp. n., A. magnioculus Liu & Chen, sp. n, A. sparsus Liu
      & Chen, sp. n. and A. thoracartus Liu & Chen, sp. n. of mycetophilus-group. Two
      newly recorded species of the mycetophilus-group are described and illustrated.
      Keys to the Chinese species of those groups are provided. 

PMID- 25947814
TI  - Review of Tumidiclava Girault (Hymenoptera: Trichogrammatidae) from Xingjiang,
      China, with description of two new species and taxonomic notes on other Holarctic
      taxa.
AB  - Four species of Tumidiclava Girault are recorded from Xinjiang Uyghur Autonomous
      Region, China. Two new species, T. buerjinica Triapitsyn & Aishan sp. nov. and T.
      tamariska Hu & Aishan sp. nov., are described; the former is also known from
      Turkmenistan and the latter from Israel. One Palaearctic species, T. subcaudata
      Nowicki, is newly recorded from China, and a key to females of the Chinese
      species is given. Taxonomic notes and illustrations are provided on these and
      also other described taxa of Tumidiclava from the Holarctic region, both sexes of
      which are keyed including the type species of the genus, T. pulchrinotum Girault
      (USA), whose male is newly described. Lectotypes are designated for Orthoneura
      bimaculata Blood & Kryger, 1928 and T. (Orthoneurella) minuscula Nowicki, 1940
      and a neotype is designated for Orthoneura bimaculata Blood, 1923. 

PMID- 25947815
TI  - Two new species of Grylloblatta Walker, 1914 (Grylloblattodea: Grylloblattidae)
      from western North America, and a neotype designation for G. rothi Gurney 1953.
AB  - Grylloblatta rothi Gurney, 1953 is redescribed and a neotype is designated from
      Cultus Mountain in the Oregon Cascades, U.S.A. Two new species of Grylloblatta
      are described, bringing the total number of Grylloblatta species to 15.
      Grylloblatta chintimini new species is described from Marys Peak in the Coast
      Range of Western Oregon, where it occurs on snowpack near the 1250 m summit.
      Grylloblatta newberryensis new species is described from Newberry Volcano in
      Central Oregon, where it is associated with snowfields overlying geologically
      young lava flows. Morphological characters, primarily derived from male
      genitalia, are presented to diagnose these species and differentiate them from
      other Grylloblatta spp. in Oregon, Washington, and California. Molecular
      sequences from the cytochrome oxidase subunit II gene suggest that significant
      divergence has occurred among these species and provide a tool to aid
      identification of juvenile and female specimens. 

PMID- 25947816
TI  - A new species of Cottus from the Onega River drainage, White Sea basin
      (Actinopterygii: Scorpaeniformes: Cottidae).
AB  - Cottus gratzianowi, a new cottid species, is described from material collected in
      the Ukhtomitsa River in the Onega River drainage, White Sea basin. It differs
      from its congeners in Europe east of the Meuse except C. koshewnikowi by having
      no transverse dark bands on the pelvic fin, a single chin canal pore, an
      incomplete lateral line not reaching behind the anal-fin insertion, and the
      position of the lateral line which is located considerably above the mid-line of
      the flank. From C. koshewnikowi distributed in the Volga (Caspian basin),
      Pechora, and Northern Dvina rivers (Arctic basin), C. gratzianowi sp. nov. can be
      distinguished by a combination of character states, the most differentiating are
      as follows: a larger eye (horizontal diameter 23-28% HL, equal to or exceeding
      snout length vs. 16-25% HL, less than snout length), a rounded caudal fin (vs.
      commonly truncated), frequent presence of one to three branched rays in median
      part of the pectoral fin (vs. usual absence), an interrupted supratemporal canal
      commissure with 4 pores (vs. non-interrupted, with 3 pores), abdominal vertebrae
      commonly 10 (vs. 11), and contrasting black blotches on all fins including pelvic
      and anal fins (vs. no blotches on pelvic and anal fins). 

PMID- 25947817
TI  - A new synonymy in the fidius group of Copris Muller 1764 (Coleoptera:
      Scarabaeidae: Scarabaeinae) and a new species from the highland grasslands of
      South Africa.
AB  - The fidius group constitutes the basal clade in a phylogeny of the Afrotropical
      members of the genus, Copris Muller, 1764. In this paper we describe Copris
      crassus Deschodt and Davis as a new species in this group. We also demonstrate
      that the distributional function between two body dimensions (lateral horn length
      and mid-line elytron length) differs between Copris fidius (Olivier 1789) and C.
      crassus. Copris bihamatus Balthasar, 1965 is also a member of the fidius group.
      Nguyen-Phung (1988) suspected that it was a synonym of C. fidius (Olivier) so we
      compare specimens of similar body size and use the distributional function
      between body dimensions to demonstrate that C. bihamatus is indeed a synonym of
      C. fidius. We provide a key for all known valid species in the fidius group,
      except C. serius Nguyen-Phung, 1987. 

PMID- 25947818
TI  - New records of Amblyomma goeldii (Acari: Ixodidae) and description of the nymphal
      stage.
AB  - Since its original description from the Amazonian region, the tick species
      Amblyomma goeldii Neumann, 1899 has been misidentified with Amblyomma rotundatum
      Koch, 1844 in different countries of the Neotropical region. Because of this,
      some authors have considered that the only confirmed records of A. goeldii were
      from French Guyana. Herein, we reviewed all specimens of A. goeldii that have
      been deposited at two tick collections in Brazil. In addition, we describe the
      nymphal stage of A. goeldii for the first time. A total of 10 unpublished records
      of the adult stage of A. goeldii are recorded from the Amazonian region of
      Brazil, confirming the occurrence of A. goeldii in this country. Except for one
      record on the snake Boa constrictor Linnaeus, all records of A. goeldii reported
      in the present study were from anteaters (Pilosa: Myrmecophagidae). Our results,
      in conjunction with previous literature records, indicate that anteaters and
      large snakes are important hosts for the adult stage of A. goeldii. The nymph of
      A. goeldii is morphologically similar to the nymphs of Amblyomma romitii Tonelli
      Rondelli, 1939, Amblyomma dissimile Koch, 1844, and A. rotundatum. We present a
      modification of a previously published taxonomic key of Amblyomma nymphs from
      Brazil, in order to perform taxonomic identification of the nymph of A. goeldii
      based on external morphology. The geographical distribution of A. goeldii appears
      to be restricted to the Amazonian region. There were no previous host records for
      the immature stages of A. goeldii, thus it is expected that the present nymphal
      description will facilitate further works on the ecology of this poorly studied
      tick species. 

PMID- 25947819
TI  - New bathyal Anachis (Neogastropoda: Buccinoidea: Columbellidae) from the
      Southwestern Atlantic, and the designation of a lectotype for A. stricta (Watson,
      1882).

PMID- 25947820
TI  - Revision of the Sundaland species of the genus Dysphaea Selys, 1853 using
      molecular and morphological methods, with notes on allied species (Odonata:
      Euphaeidae).
AB  - The Sundaland species of the genus Dysphaea were studied using molecular and
      morphological methods. Four species are recognized: D. dimidiata Selys, D. lugens
      Selys, D. ulu spec. nov. (holotype ?, from Borneo, Sarawak, Miri division, Upper
      Baram, Sungai Pejelai, Ulu Moh, 24 viii 2014; deposited in RMNH) and D. vanida
      spec. nov. (holotype ?, from Thailand, Ranong province, Khlong Nakha, Khlong Bang
      Man, 12-13 v 1999; deposited in RMNH). The four species are described and
      illustrated for both sexes, with keys provided. The type specimens of the four
      Dysphaea taxa named by E. de Selys Longchamps, i.e. dimidiata, limbata,
      semilimbata and lugens, were studied and their taxonomic status is discussed.
      Lectotypes are designated for D. dimidiata and D. limbata. D. dimidiata is
      recorded from Palawan (the Philippines) for the first time. A molecular analysis
      using three markers (COI, 16S and 28S) is presented. This includes specimens of
      three Sundaland species of the genus (D. lugens missing) and two congeners from
      other regions (D. basi-tincta and D. gloriosa). Notes and photographs of the male
      holotype of D. walli Fraser (from Maymyo, Burma) are provided. 

PMID- 25947821
TI  - First description of winged stages of Thraulobaetodes Elouard & Hideux 1991 and
      reclassification of Rhithrocloeoninae (Ephemeroptera, Baetidae).
AB  - Larvae, subimagoes, imagoes of both sexes and eggs of Thraulobaetodes cumminsorum
      Elouard & Hideux 1991 are described based on reared material from north-west of
      Zambia. Structure and development of genitals testify that Thraulobaetodes
      Elouard & Hideux 1991 belongs to Rhithrocloeoninae Kluge 2012. According to the
      newly suggested classification, Rhithrocloeoninae are divided into
      Thraulobaetodini tribus n. and holophyletic taxon Rhithrocloeonini, which
      includes Bugilliesia Lugo-Ortiz & McCafferty 1996, Mutelocloeon Gillies & Elouard
      1990 and Rhithrocloeon Gillies 1985 (including subgenus Kivuiops Lugo-Ortiz &
      McCafferty 2007). Structure of egg chorion of Bugilliesia, Mutelocloeon and
      Rhithrocloeon is described for the first time. Additional imaginal and
      subimaginal characters of Mutelocloeon are reported. 

PMID- 25947822
TI  - Description of immatures of Chelymorpha reimoseri Spaeth, 1928 (Coleoptera:
      Chrysomelidae: Cassidinae: Mesomphaliini).
AB  - Immature stages of Chelymorpha reimoseri Spaeth, 1928 are described in detail,
      including line drawings, chaetotaxy, sculpture of integument, and SEM photos of
      morphological details. It is the first detailed description of immatures in the
      genus Chelymorpha Chevrolat, 1836 and the fourth in the tribe Mesomphaliini
      Chapuis, 1875 which include chaetotaxy of the body. Diagnostic characters for
      this species in comparison with other described larvae and pupae of the genus
      Chelymorpha are discussed. Some remarks on the biology of Ch. reimoseri, are also
      given. 

PMID- 25947823
TI  - Type specimens of Colletes Latreille (Hymenoptera, Colletidae) deposited in the
      Zoological Institute of the Russian Academy of Sciences, St. Petersburg, with
      description of a new species.
AB  - The type specimens of Colletes Latreille 1802 deposited in the Zoological
      Institute, Russian Academy of Sciences (St. Petersburg) are reviewed. Precise
      information about types of 30 taxa are provided (12 described by J. Noskiewicz; 9
      by F. Morawitz; 8 by M. Kuhlmann and M. Proshchalykin; 1 by H. Friese).
      Lectotypes are designated here and illustrated for the following six nominal
      taxa: Colletes alpinus Morawitz 1872, C. caspicus Morawitz 1874, C. montana
      Morawitz 1876, C. squamosus Morawitz 1877, C. tuberculatus Morawitz 1893, and C.
      wollmanni Noskiewicz 1936. Colletes alpinus was synonymized with C. impunctatus
      Nylander 1852 but is now recognized as a synonym of C. floralis Eversmann 1852.
      Colletes morawitzensis Kuhlmann & Proshchalykin, sp. nov. is described based on a
      male specimen from Turkmenistan and deposited in the Morawitz collection. 

PMID- 25947824
TI  - Redescription of some poorly known species of Cytaea Keyserling, 1882 (Araneae:
      Salticidae), with new synonymies.
AB  - Eight nominal species of Cytaea were studied. The poorly known Cytaea fibula
      Berland, 1938, C. flavolineata Berland, 1938 and C. oreophila Simon, 1902 are
      redescribed, diagnosed and illustrated. Cytaea aeneomicans Simon, 1902 and C.
      guentheri Thorell, 1895 are synonymized with C. dispalans (Thorell, 1892), while
      C. whytei Proszynski & Deeleman-Reinhold, 2010 is synonymized with C. haematica
      Simon, 1902. 

PMID- 25947825
TI  - Two peculiar new species of Otites Latreille 1804 (Diptera: Ulidiidae) with
      reduced phallus.
AB  - Two new closely related species of the genus Otites are described and
      illustrated: O. freidbergi n. sp. from Israel, and O. friedmani n. sp. from
      Cyprus. The two species exhibit unusual male terminalia for Otites and other
      Otitini. Laboratory behavioral observations on live O. freidbergi individuals
      showed unusually long copulation duration compared to other examined Otitini
      species. 

PMID- 25947826
TI  - Discovery of second new species of the genus Spiniphilus Lin & Bi, and female of
      Heterophilus scabricollis Pu with its biological notes (Coleoptera: Vesperidae:
      Philinae: Philini).
AB  - A new philine species of the genus Spiniphilus Lin & Bi, 2011, S. xiaodongi sp.
      nov. is described from Yunnan, China. The female of Heterophilus scabricollis Pu,
      1988 is described for the first time with its biological and ecological data. 

PMID- 25947827
TI  - Discovery of the genus Ancystrocerus Raffray in China, with description of a new
      species (Coleoptera: Staphylinidae: Pselaphinae).
AB  - The tmesiphorine genus Ancystrocerus Raffray, 1893 is newly recorded in China,
      and a new species, A. chinensis Yin, Wang & Li sp. n., is described, figured, and
      compared with its congeners. New collection data of a previously described
      species Tmesiphodimerus sinensis Yin & Li is given. 

PMID- 25947828
TI  - Two new species of Phlogophora Treitschke (Lepidoptera: Noctuidae) from China and
      Vietnam.

PMID- 25947829
TI  - Pristionchus Scratchpads--an online platform for taxonomy, systematics and
      phylogeny.

PMID- 25947830
TI  - Redefinition of Acanthosoma and taxonomic corrections to its included species
      (Hemiptera: Heteroptera: Acanthosomatidae).
AB  - The genus level diagnostic characters of Acanthosoma Curtis, 1824, Anaxandra
      Stal, 1876, and Sastragala Amyot & Serville, 1843 (Hemiptera: Heteroptera:
      Acanthosomatidae) are discussed. The synonymy of Acanthosoma and Anaxandra
      proposed by Kumar (1974) is supported. Acanthosoma and Sastragala are redefined
      and recognized as valid genera. The identities of various species of Acanthosoma
      are clarified based on their type materials, their diagnostic characters are
      discussed and several misidentifications in previous works are corrected. The
      following new or reinstated combinations and new subjective synonymies are
      proposed: Acanthosoma haemorrhoidale haemorrhoidale (Linnaeus, 1758) =
      Acanthosoma proximum Dallas, 1851, syn. nov. = Acanthosoma difficile Dallas,
      1851, syn. nov. = Acanthosoma dubium Dallas, 1851, syn. nov.; Acanthosoma
      firmatum (Walker, 1868), comb. nov. (transferred from Sastragala) = Acanthosoma
      giganteum Matsumura, 1913, syn. nov.; Acanthosoma murreanum (Distant, 1900),
      comb. nov. (transferred from Sastragala) = Acanthosoma acutangulata Liu, 1979,
      syn. nov. = Sastragala neoelongata Ahmad & Moizuddin, 1990, syn. nov.;
      Acanthosoma rufispinum (Distant, 1887), comb. nov. (transferred from Sastragala)
      = Sastragala minuta Ahmad & Moizuddin, 1990, syn. nov.; Acanthosoma tauriforme
      (Distant, 1887) = Anaxandra longispina Liu, 1987, syn. nov.; Acanthosoma hampsoni
      (Distant, 1900), comb. nov. (transferred from Sastragala); Acanthosoma
      labiduroides Jakovlev, 1880 = Acanthosoma coralliferum Horvath, 1889, syn. nov. =
      Acanthosoma zanthoxylum Hsiao & Liu, 1977, syn. nov.; Acanthosoma forfex Dallas,
      1851 = Acanthosoma distinctum Dallas, 1851, syn. nov.; Acanthosoma rufescens
      Dallas, 1851, comb. restit. = Acanthosoma elongatum Dallas, 1851, syn. nov. =
      Anaxandra hamata Reuter, 1881, syn. nov.; Acanthosoma nigricorne Walker, 1868 =
      Acanthosoma nigrospina Hsiao & Liu, 1977, syn. nov.; Acanthosoma alaticorne
      Walker, 1868, comb. restit. = Anaxandra laticollis Hsiao & Liu, 1977, syn. nov.
      New combinations resulting from synonymization of Anaxandra with Acanthosoma:
      Acanthosoma sichuanense (Liu, 1980), comb. nov., A. montanum (Liu, 1987), comb.
      nov. Species transferred to Sastragala Amyot & Serville, 1843: Sastragala
      nigrolineata (Stal, 1876), comb. nov.; S. sigillata (Stal, 1876), comb. nov.; S.
      versicolor Distant, 1910, comb. restit.; S. yunnana (Hsiao & Liu, 1977), comb.
      nov.; to Elasmostethus Fieber, 1860: Elasmostethus singhalensis (Distant, 1902),
      comb. nov. Lectotypes are designated for the following species: Acanthosoma: A.
      difficile, A. distinctum, A. dubium, A. elongatum, A. forfex, A. proximum;
      Anaxandra: A. hamata, A. nigrocornuta Reuter, 1881, A. tauriformis; Sastragala:
      S. murreeana, S. rufispina. A neotype is designated for Anaxandra montana. New
      country records: Acanthosoma alaticorne and A. rufispinum: Nepal; A. forfex:
      Burma (Myanmar); A. labiduroides: Burma (Myanmar) and Vietnam; A. montanum: Laos
      and Vietnam; A. murreeanum: India, Thailand; A. nigricorne: Nepal, Burma
      (Myanmar) and Vietnam; A. rufescens: Pakistan, Nepal, Taiwan, Burma (Myanmar),
      Thailand, Laos and Vietnam.

PMID- 25947831
TI  - Calcareous sponges of Indonesia.
AB  - The calcareous sponges collected during Indonesian-Dutch research projects,
      incorporated in the collections of the Naturalis Biodiversity Center (formerly
      the Rijksmuseum van Natuurlijke Historie and the Zoologisch Museum of the
      University of Amsterdam), are described and discussed. A total of 37 species were
      distinguished, of which 16 are new to science, while several others are very
      poorly known. The new species are Clathrina purpurea sp.nov., Clathrina beckingae
      sp.nov., Clathrina sororcula sp.nov., Arthuria tubuloreticulosa sp.nov., Ernstia
      indonesiae sp.nov., Ernstia chrysops sp.nov., Ernstia klautauae sp.nov., Ernstia
      naturalis sp.nov., Ascandra kakaban sp.nov., Ascandra crewsi sp.nov., Ascaltis
      angusta sp.nov., Pericharax orientalis sp.nov., Sycetta vinitincta sp.nov.,
      Anamixilla singaporensis sp.nov., Grantessa borojevici sp.nov. and Grantessa
      tenhoveni sp.nov. An additional six species reported from Indonesia, but not
      represented in our material, are briefly characterized.

PMID- 25947832
TI  - Revision of the frog fly genus Caiusa Surcouf, 1920 (Diptera, Calliphoridae),
      with a note on the identity of Plinthomyia emimelania Rondani, 1875.
AB  - The Oriental, Australasian and Oceanian genus Caiusa Surcouf, 1920 is revised,
      species concepts being based on male and female genitalia. A key to males for all
      known species, and a key to females for all except one are given. All relevant
      types still in existence have been studied, complete synonymies given and the
      geographical distribution reconsidered. The eight species included in the genus
      are: Caiusa borneoensis sp. nov. (Malaysia, Thailand, Vietnam); Caiusa coomani
      Seguy, 1948 (China, Malaysia, Singapore, Thailand, Vietnam); Caiusa indica
      Surcouf, 1920 (Australia, Cambodia, India, Indonesia, Malaysia, Papua New Guinea,
      Philippines, Singapore, Solomon Islands, Sri Lanka, Thailand, Vietnam); Caiusa
      karrakerae sp. nov. (Malaysia, Thailand); Caiusa kurahashii sp. nov. (Indonesia,
      Japan, Philippines); Caiusa pooae sp. nov. (Thailand); Caiusa testacea Senior
      White, 1923 (India, Nepal, Sri Lanka) and Caiusa violacea Seguy, 1925, stat. rev.
      (Cambodia, China, Laos, Malaysia, Taiwan, Thailand, Vietnam). A lectotype is
      designated for Caiusa indica to fix the interpretation of the name. Caiusa
      nigronitens Senior-White, 1923, syn. nov. and Caiusa surcoufi Bezzi, 1927, syn.
      nov. are established as junior synonyms of Caiusa indica. Caiusa violacea is
      correctly diagnosed and errors in the original description of the female holotype
      are pointed out. Caiusa dubiosa Villeneuve, 1927 is established as a junior
      synonym of C. violacea, syn. nov. Seven Caiusa species have been reared from the
      egg mass of various species of frogs. The reproductive mode of the eighth
      species, i.e., C. indica, is unknown. Five species, i.e., C. borneoensis, C.
      coomani, C. karrakerae, C. kurahashii and C. violacea have been reared from one
      or more of the foam nesting frog species Chiromantis nongkhorensis (Cochran,
      1927), Polypedates leucomystax (Gravenhorst, 1927), Polypedates megacephalus
      Hallowell, 1861, Rhacophorus annamensis Smith, 1924, Rhacophorus dulitensis
      Boulenger, 1892, Rhacophorus kio Ohler & Delorme, 2005 and Rhacophorus owstoni
      (Stejneger, 1907) all belonging in the family Rhacophoridae in Anura. These five
      Caiusa species all have a specialised ovipositor tip, with small spine-like setae
      on the ST8 and the hypoproct, probably enabling the flies to oviposit on a foam
      nest with a hardened outer surface. They form a monophyletic group on account of
      these features of the ovipositor, unique in the Oestroidea. The sixth species, C.
      testacea, has been reared from a frog egg mass, the frog species being unknown.
      Its ovipositor structure is also unknown. The seventh species, C. pooae, has been
      reared once from the jelly-like egg mass of Feihyla hansenae (Cochran, 1927),
      also in Rhacophoridae. Caiusa pooae females do not have spine-like setae on the
      ovipositor, a fact correlated with the soft outer surface of the jelly-like egg
      mass on which a C. pooae female had oviposited. The extreme rarity of C. pooae
      oviposition on Feihyla hansenae egg masses may indicate that this fly perhaps has
      another, unknown, regular oviposition substrate. Caiusa pooae and C. indica make
      up a second monophyletic group within Caiusa. Caiusa indica, the most common and
      most widespread species of the genus, has an ovipositor structure similar to C.
      pooae. Its breeding substrate is unknown and it occurs both within and outside
      the distributional area of Rhacophoridae. Possibly both C. indica and C. pooae
      share a regular oviposition substrate that has still to be discovered. The
      holotype female of Plinthomyia emimelania Rondani, 1875 from Sarawak is
      established as a member of the genus Bengalia Robineau-Desvoidy, 1830, thus
      Plinthomyia Rondani, 1875 becomes a junior synonym of Bengalia Robineau-Desvoidy,
      1830, syn. nov. It is removed from the synonymy of Phumosia Robineau-Desvoidy,
      1830.

PMID- 25947833
TI  - A review of the New World Coproica (Diptera: Sphaeroceridae) with a description
      of 8 new species.
AB  - The New World species of Coproica Rondani, 1861 (Diptera: Sphaeroceridae) are
      reviewed on the basis of over 17,000 examined specimens. The genus is divided
      into three major clades: the C. acutangula, C. vagans, and C. urbana species
      groups. Eight new species (C. bifurcata, C. bispatha, C. brachystyla, C.
      diabolica, C. emarginata, C. galapagosensis, C. novacula, and C. testudinea) are
      described, and redescriptions are provided for eleven additional species.
      Included are two keys (one for the twenty New World species only and one for all
      described species), updated New World distribution records, and illustrations of
      male and female genitalic structures.

PMID- 25947834
TI  - The genus Sphegina Meigen (Diptera, Syrphidae) in a biodiversity hotspot: the
      thirty-six sympatric species in Kambaiti, Myanmar.
AB  - The material of Sphegina collected by Rene Malaise in Kambaiti, Myanmar, in 1934
      includes S. (Sphegina) kumaoniensis Mutin and the following 35 new species: S.
      (Sphegina) uncinata, S. (Asiosphegina) achaeta, S. (A.) adusta, S. (A.)
      atricolor, S. (A.) bidens, S. (A.) bilobata, S. (A.) carinata, S. (A.) cerina, S.
      (A.) crassispina, S. (A.) crucivena, S. (A.) culex, S. (A.) cultrigera, S. (A.)
      ensifera, S. (A.) falcata, S. (A.) forceps, S. (A.) forficata, S. (A.) furva, S.
      (A.) gigas, S. (A.) index, S. (A.) malaisei, S. (A.) minuta, S. (A.) mirifica, S.
      (A.) nasuta, S. (A.) pollex, S. (A.) pollinosa, S. (A.) parvula, S. (A.) pusilla,
      S. (A.) radula, S. (A.) raduloides, S. (A.) siculifera, S. (A.) simplex, S. (A.)
      sinesmila, S. (A.) subradula, S. (A.) trichaeta and S. (A.) trispina. A key to
      the studied species is given. The world fauna of Sphegina now comprises 120
      species.

PMID- 25947835
TI  - Redescription of Bythotrephes longimanus Leydig, 1860 and B. cederstromii
      Schodler, 1877 (Crustacea: Cladocera: Onychopoda), with notes on the morphology
      and systematics of the genus Bythotrephes Leydig, 1860.
AB  - Two core species of the genus Bythotrephes Leydig, B. longimanus Leydig and B.
      cederstromii Schodler, are redescribed on the basis of the type material,
      topotypic material, and other materials from Western and Northern Europe. They
      were investigated with an application of detailed morphological analysis,
      including intra- and interpopulation variability and the original scheme of
      morphometric measurements. The neotype of B. longimanus was selected from the
      topotypic population of the species from Bodensee (Switzerland-Germany). The
      taxonomy of B. cederstromii and of the whole genus is complicated by the presence
      of a variety of similar forms with intermediate morphology supposed to be
      interspecific hybrids, which much confused previous researches. The evolutionary
      transformations of some morphological structures, such as thoracic limbs,
      abdomen, and caudal process, are analyzed and discussed. In particular, it is
      suggested that the internal side of the endopodites of the thoracic limbs of the
      second-fourth pairs grew in proximal direction, occupying the part of protopodite
      with the "gnathobasic" process, which remains to be homologous to those of the
      thoracic limbs of the first pair. The strongly reduced thoracic limbs of the
      fourth pair lost two terminal segments and have proved to be represented by three
      segments, two proximal of which are those of protopodite, while the third
      terminal segment is composed of the fused distal part of the protopodite and the
      first proximal endopodital segment, bearing transformed and specifically arranged
      setae. The specificity of the "gnathobasic" processes of Bythotrephes is that
      they are the derivatives of the second, not of the first, inner endite of the
      thoracic limb and for this reason they are not homologues to the gnathobases of
      other cladocerans and should be called pseudognathobases.The same position of the
      "gnathobasic" processes is characteristic for other Onychopoda, which stresses
      the uniqueness of the representatives of the order among Cladocera and the whole
      class Branchiopoda. The abdomen of Bythotrephes was found to be three-segmented,
      but the third distal segment has proved to be transformed and fused with the
      postabdomen, participating in the formation of a long and massive caudal process.
      The comparison of morphological features of Bythotrephes and Leptodora clearly
      shows their independent homoplasic evolutionary development and distant
      phylogenetic position. According to new available data, the range of B.
      longimanus embraces large and deep lakes of Switzerland, Southern Germany, North
      Italy, Austria, and Great Britain, whereas B. cederstromiis. str. is certainly
      known only in the south of Sweden (probably also in Finland). All other B.
      cederstromii-like forms, supposed to be interspecific hybrids, are much more
      widely distributed in Eurasia from Northern Europe and Central European Russia to
      the Lower Volga River and Yakutia in Eastern Siberia. It is suggested that just
      these hybrids invaded and conquered the North American inland waters. 

PMID- 25947836
TI  - Comments on the biology of Sciodrepoides watsoni watsoni (Spence, 1813) with
      descriptions of larvae and pupa (Coleoptera: Leiodidae: Cholevinae).
AB  - The late-instar larva of Sciodrepoides watsoni watsoni is redescribed and the
      egg, first and second instar and pupa are described for the first time. Immature
      stages habitus, chaetotaxy, detailed illustrations and details of life cycle are
      provided. Previous descriptions of larva of S. watsoni are discussed. The
      structures of larvae of S. watsoni are compared with those of other known larvae
      of Cholevinae. 

PMID- 25947837
TI  - Synonymy of Crossodactylus bokermanni Caramaschi & Sazima, 1985 with
      Crossodactylus trachystomus (Reinhardt & Lutken, 1862) and description of a new
      species from Minas Gerais, Brazil (Anura: Hylodidae).
AB  - The analysis of the external morphology variation in Crossodactylus bokermanni,
      C. trachystomus, and in unidentified specimens from 14 localities along the
      southern region of the Serra do Espinhaco, state of Minas Gerais, Brazil,
      revealed that all of these forms belong to the same taxon. Crossodactylus
      bokermanni is considered a junior synonym of C. trachystomus, whose holotype is
      redescribed and figured. The population from Serra da Canastra, western Minas
      Gerais, previously referred to as Crossodactylus cf. trachystomus, is herein
      described and figured as Crossodactylus franciscanus. Its advertisement call is
      redescribed and compared to those known for the genus. 

PMID- 25947838
TI  - Swedish Plectida (Nematoda). Part 9. The genus Leptolaimoides Vitiello, 1971.
AB  - Three known and two new species of Leptolaimoides are described from bottom
      sediments collected in Skagerrak off the west coast of Sweden. The following
      known species are redescribed: Leptolaimoides haploopis Jensen, 1978, L.
      tubulosus Vitiello, 1971 and L. hexatubulosus Hoang Lai-Phu et al., 2009.
      Leptolaimoides filicaudatus sp. n. is characterised by the 431-543 um long body;
      cephalic sensilla papilliform; amphid 23-26 um long, located 9-10 um from
      anterior end; first body pore located 35-37 um from anterior end; lateral field
      simple along most of body, areolated on tail, arising 36-40 um from anterior end;
      female without supplements, vagina without pars refringens, vulva midventral;
      male without tubular and without alveolar supplements; spicules arcuate and 16 um
      long. Leptolaimoides leptomicron sp. n. is characterised by the 776-847 um long
      body; cephalic sensilla papilliform; amphid 15-17 um long, located 9-13 um from
      anterior end; first body pore located 40-46 um from anterior end; lateral field
      areolated, arising 26-28 um from anterior end; female without supplements, vagina
      without pars refringens, vulva midventral; male with three tubular and without
      alveolar supplements, spicules arcuate and 28-29 um long. The diagnosis of the
      genus Leptolaimoides is emended and a tabular compendium and dichotomous
      identification key to species of the genus Leptolaimoides are provided. 

PMID- 25947839
TI  - Arrhopalites potapovi sp. nov. (Collembola, Symphypleona) from Russia.
AB  - A new springtail species of the family Arrhopalitidae, Arrhopalites potapovi sp.
      nov., is described. It belongs to the caecus species group characterized by
      3,2,1,1,1 anterior setae on dens and separates from Arrhopalites caecus
      (Tullberg) and other congeners by strongly differentiated cuticular spines on
      sixth abdominal segment, shape of female subanal appendages and foot complex. It
      was found under the loose bark of trees from two localities along Lake Baikal and
      it is the second representative of the genus Arrhopalites Borner sensu stricto in
      Russia. 

PMID- 25947841
TI  - Description of larva and puparium of Oplodontha rubrithorax (Diptera:
      Stratiomyidae) from the Oriental Region.
AB  - This is the first description of larva and puparium of Oplodontha rubrithorax
      (Macquart, 1838) from the Oriental Region. Larvae were found at a hot spring in
      North Thailand. The morphological features and cuticular structures of the larva
      are documented by drawings and SEM micrographs and the main characters are
      compared with the European O. viridula (Fabricius, 1775), the only described
      larva of this genus. Differences between larvae of both species were only found
      in pubescence. The characteristic, somewhat dilated and slightly clavate hairs on
      the dorsal surface of the body segments of O. viridula larva are apparently
      lacking in the larva of O. rubrithorax. 

PMID- 25947840
TI  - Molecular phylogeny of Metanoeina net-winged beetles identifies Ochinoeus, a new
      genus from China and Laos (Coleoptera: Lycidae).
AB  - The molecular hypothesis on relationships of Metanoeina lineages is presented and
      results are compared with morphology. A new genus Ochinoeus is proposed for four
      East Palearctic and Oriental species. Ochinoeus is recovered as a sister lineage
      to Matsudanoeus Sklenarova et al., 2014 and differs from related genera in
      morphology of genitalia and incomplete secondary elytral costae. We show, that
      the structure of elytral costae, although highly homoplastic across
      Metriorrhynchini, can be used for identification of Ochinoeus. The geographic
      distribution of Metanoeina is limited to the eastern parts of the Palaearctic and
      Oriental regions. The reconstruction of ancestral ranges identifies continental
      Eastern Asia as the centre of generic diversity of Metanoeina and suggests the
      dispersal from continental Asia to the southern part of the Oriental region, i.e.
      to the Sundaland and Philippines. Among Metanoeina lineages, only Metanoeus
      Waterhouse, 1878 contains higher number of species. The following four species
      are described: Ochinoeus huaphanensis sp. nov., O. hainanensis sp. nov., O.
      habashanensis sp. nov., and O. xunyanbaensis sp. nov.. 

PMID- 25947842
TI  - A new species of Melobasina (Ulaikoilia Bily & Kuban) (Coleoptera: Buprestidae)
      from Sulawesi.
AB  - A new species Melobasina (Ulaikoilia) jennyae sp. n. (Coleoptera: Buprestidae) is
      described from Sulawesi, Indonesia. A key is provided to distinguish the new
      species from the other two known species. 

PMID- 25947843
TI  - A new Nalassus Mulsant, 1854 (Coleoptera: Tenebrionidae: Helopini), the first
      representative of the genus from the Russian Far East.
AB  - A new species, Nalassus (Helopocerodes) olgae sp. n., is described from Primorsky
      Krai in the Russian Far East. A new combination is established: Nalassus
      (Helopocerodes) magyari (Kaszab, 1968), comb. n. The new species is similar to N.
      magyari but differs in the sculpture of the metaventrite, larger body and widely
      flattened lateral sides of the pronotum. 

PMID- 25947844
TI  - Ctenocheloides boucheti n. sp., a new ghost shrimp from Papua New Guinea
      (Decapoda, Axiidea, Ctenochelidae).
AB  - Ctenocheloides boucheti, the third species in this widespread but rare genus, is
      described from Papua New Guinea. It differs from the others in having more acute
      distal lobe on the eyestalk, more prominent distal bifid tooth on the cheliped
      ischium, longer cheliped fingers, shorter telson and the antennular and antennal
      peduncles reaching similar lengths. 

PMID- 25947845
TI  - Description of two unknown females of Epeus Peckham & Peckham from China
      (Araneae: Salticidae).
AB  - The jumping spider genus Epeus Peckham & Peckham presently includes 15 species,
      mainly from South and Southeast Asia (World Spider Catalog 2015). Species of this
      genus have the cymbium of male palp flattened and elongated, with a basal
      apophysis retrolaterally, pointing postero-ventrally; tegulum with a tongue-like
      process; filiform embolus; and epigyne with long copulatory ducts with several
      loops. 

PMID- 25947846
TI  - Immatures of Palaearctic species of the weevil genus Sibinia (Coleoptera,
      Curculionidae): new descriptions and new bionomic data with suggestions on their
      potential value in a phylogenetic reconstruction of the genus.
AB  - The larvae and pupae of six species of the Palaearctic genus Sibinia Germar, 1817
      are described in detail for the first time. Five of them develop in seeds of
      Caryophyllaceae and belong to Sibinia (s. str.): S. attalica Gyllenhal, 1835; S.
      femoralis Germar, 1824; S. tibialis Gyllenhal, 1835; and S. viscariae (Linnaeus,
      1760), which are included in the S. femoralis group, and S. sicana Ragusa, 1908,
      which is included in the S. unicolor Fahraeus, 1843 group. The sixth species is
      S. sodalis Germar, 1824, which develops in seeds of Plumbaginaceae and belongs to
      the subgenus Dichotychius Bedel, 1885. The larvae and pupae of these species are
      compared with those previously described for some species of the third subgenus,
      Microtychius Casey, 1910 from the Americas. Some larval characters, but no pupal
      ones, are useful to support the three subgenera and the two previously mentioned
      groups of Sibinia s. str., which were previously postulated based on a few adult
      morphological characters. The immatures of Sibinia are also compared with those
      of the closely related genus Tychius Germar, 1817, providing some distinctive
      characters between both genera. New bionomic data on larval and pupal development
      and adult emergence are reported for all the described species. These data
      suggest that species in this genus are highly homogeneous in life history traits.

PMID- 25947847
TI  - Revision of the New World species of the genus Pelecorhynchus Macquart, 1850
      (Diptera: Pelecorhynchidae).
AB  - The New World species of the genus Pelecorhynchus Macquart, all of which are only
      known from Chile, are revised. Two new species are described, Pelecorhynchus
      hualqui sp. nov. and Pelecorhynchus toltensis sp. nov. All nine New World species
      in the genus are redescribed and illustrated, and a key to the species is
      provided. 

PMID- 25947848
TI  - Redescription of Coronatella poppei (Richard, 1897) (Crustacea, Branchiopoda,
      Chydoridae) and a revision of the genus in Brazil, with descriptions of new taxa.
AB  - The description of the genus Coronatella Dybowski & Grochowski, 1894 (Cladocera:
      Chydoridae: Aloninae) pointed towards the need for a revision of species on a
      worldwide scale. For the Neotropical region, the main challenge noted was the
      redescription of Coronatella poppei (Richard, 1897). We redescribed this species
      and revised populations from Brazil that had previously been assumed to be Alona
      poppei (= C. poppei). Our results indicate that C. poppei is distributed in the
      southern part of South America. In Brazil, two other taxa are recognized,
      Coronatella paulinae sp.nov. and Coronatella serratalhadensis sp.nov., which are
      morphologically distinguished both from each other and from C. poppei. These
      species also have different geographic distributions. The Brazilian Coronatella
      fauna also comprises Coronatella monacantha (Sars, 1901) and a related species,
      Coronatella undata sp.nov. Our results point towards a previously unknown high
      diversity of Coronatella in the Neotropical region with several implications for
      to biogeography of the genus. 

PMID- 25947849
TI  - Zemacrosaldula, a new genus of Saldidae (Hemiptera: Heteroptera) from New
      Zealand: taxonomy, geographic distribution, and biology.
AB  - Zemacrosaldula, new genus, is described with Salda australis White, 1876, as type
      species, resulting in the following new combination Zemacrosaldula australis
      (White, 1876). Three new species are described: Zemacrosaldula kapekape new
      species, Z. whakarunga new species, Z. pangare new species. A revision of the
      taxonomy of all taxa is presented. Species are keyed. Morphological descriptions
      are provided together with illustrations emphasising the most significant
      diagnostic features of external morphology and male genitalia. Information is
      given on synonymy, type specimens, material examined, geographic distribution and
      biology. 

PMID- 25947850
TI  - New Austrognathiidae (Gnathostomulida: Conophoralia) from Hong Kong and Japan:
      microscopic anatomy, ultrastructure and evolutionary implications.
AB  - We describe two new species, Austrognathia glandifera and Austrognatharia
      orientis using observations on squeezed, live specimens as well as histological
      sections and transmission electron microscopy. The protonephridia of
      Austrognatharia orientis are composed of a terminal cell, a canal cell, and a
      nephroporus cell. The monociliated terminal cell constitutes the so-called
      filtration area. The canal cell harbors the lacunar system and the
      protonephridial duct, which is surrounded by six filamentous rods, which
      originate external to and in between the microvilli of the terminal cell and
      stretch along the entire length of the canal cell. The female copulatory organs
      of the investigated species are very different. Austrognathia glandifera has a
      bursa and a vagina whereas A. orientis only has a weakly defined bursal tissue
      and no detectable vagina. The bursa is divided into an anterior and a posterior
      part; at the anterior end a special area is formed by interdigitations of the
      cells of the bursal wall. The male copulatory organs in the Conophoralia are
      uniform, composed of an anterior, glandular portion consisting of a proximal part
      with medium-grained and a distal part with coarse-grained appearance and a penis
      that is delineated by a basal lamina and has an ejaculatory duct as well as a
      gonopore. Parenchymal cells are present and serve to embed the bursa and the male
      copulatory organ dorsolaterally. Our data on the fine structure of various
      tissues indicate that the Conophoralia are the "less derived" sister taxon of the
      Scleroperalia. 

PMID- 25947851
TI  - A review of the ant genus Myrmecorhynchus (Hymenoptera: Formicidae).
AB  - The Australian endemic ant genus Myrmecorhynchus is reviewed. The genus is known
      from three species (M. carteri Clark, M. emeryi Andre and M. nitidus Clark) which
      are restricted to eastern and southern Australia. Myrmecorhynchus musgravei Clark
      and M. rufithorax Clark are newly synonymised with M. emeryi Andre. All species
      are found in forested areas where they nest arboreally or, less commonly, in
      soil. Foraging occurs primarily on vegetation and tree trunks. 

PMID- 25947852
TI  - A new species Micrarctia kautti (Lepidoptera: Erebidae, Arctiinae) from West
      China.
AB  - A new tiger moth, Micrarctia kautti sp. n., from southwest China, Sichuan is
      described. A diagnostic comparison with Micrarctia trigona (Leech, 1899) is
      provided. During recent years the Chinese Arctiini have been intensively
      collected and explored (Dubatolov, 1996a; Dubatolov, 1996b; Dubatolov, 2003;
      Dubatolov, Kishida & Wu, 2005; Fang & Cao, 1984; Fang, 2000 and numerous other
      publications) so the discovery of a striking new species by Sergey Murzin in the
      Dafengding Mountains, Sichuan Province, was most unexpected. Institutional
      acronyms used are as follows: ASV = Aidas Saldaitis (Vilnius, Lithuania); KNE =
      Kari Nupponen (Espoo, Finland); PKT = Peter Kautt (Tubingen, Germany); RMB =
      Ramon Macia (Barselona, Spain); WIGJ = World Insect Gallery (Joniskis,
      Lithuania).

PMID- 25947853
TI  - What is Neoschidium Mukherjee, Ambrose, Saha, and Bal, 2014 (Hemiptera:
      Reduviidae: Emesinae: Metapterini)? A reflection on taxonomic practices.
AB  - Good taxonomic practice permits not only to adequately document the rapidly
      diminishing biodiversity of our planet (Wheeler 2008), but also let us set the
      foundations for phylogenetic assessments among groups of taxa, allowing a more
      deeply and proper understanding of the biota (Wheeler 2007). Therefore, any
      taxonomic problems will hinder not only phylogenetic approaches but conservation
      efforts as well (Dubois 2003; Mace 2004; Wheeler et al. 2012). 

PMID- 25947854
TI  - The correct spelling of the specific name of the Double-barred Finch, Taeniopygia
      bichenovii (Vigors & Horsfield, 1827) (Passeriformes: Estrildidae).

PMID- 25947855
TI  - Elhamma Walker (Lepidoptera: Hepialidae) revisited: adult morphology, assessment
      of recently proposed synonyms and descriptions of two species.
AB  - I revise the Australian-New Guinean ghost moth genus Elhamma. Two recent
      synonymies are assessed, and two new species from New Guinea, E. grehani sp. nov.
      and E. viettei sp. nov. are described. I provide an updated diagnosis for the
      genus and conclude that the presence of only 2 M-veins in the hind wing in both
      sexes (when females are known) and a strongly cup-shape juxta in the male
      genitalia are unique diagnostic characters among Hepialidae. I give a detailed
      description of the adult morphology based on male E. australasiae, and provide a
      key to all known species based on adult male characters. 

PMID- 25947856
TI  - Morphological characterization of some representative species of the genus
      Loxoblemmus (Orthoptera: Gryllidae; Gryllinae; Gryllini) from India.
AB  - Morphological characterization of some common species of the genus Loxoblemmus
      (Gryllidae: Gryllinae) from India is presented. In all, 5 species were identified
      that included two, Loxoblemmus equestris Saussure and Loxoblemmus haani Saussure,
      from the sub-humid regions of Rajasthan (South West India) and Madhya Pradesh
      (Central India); while three species, Loxoblemmus taicoun Saussure, Loxoblemmus
      jacobsoni Chopard and Loxoblemmus intermedius Chopard from the humid hilly
      regions of Meghalaya and Assam (North East India). Of the 5 reported species,
      based on the comparative linear measurements, L. haani is relatively larger than
      the other species encountered. 

PMID- 25947857
TI  - Description of a new species of Aclastus Forster (Hymenoptera: Ichneumonidae:
      Cryptinae) from the Peruvian Andes, with dimorphic females.
AB  - The aim of this paper is to describe and illustrate a new species of Aclastus
      with dimorphic females and to provide the diagnostic characters to distinguish it
      from Holarctic species of the genus. In addition, we provide data on the habitat
      and phenology of the species. 

PMID- 25947858
TI  - The New World genus Rhinoleucophenga (Diptera: Drosophilidae): new species and
      notes on occurrence records.
AB  - The genus Rhinoleucophenga Hendel comprises 26 nominal species with New World
      distribution. In the present study, two new species are described from samples in
      the Pampa and Caatinga biomes in Brazil, R. punctuloides sp. nov. and R.
      trivisualis sp. nov., respectively. Rhinoleucophenga punctuloides sp. nov. is a
      sibling species of R. punctulata Duda. Furthermore, two females of R. joaquina
      Schmitz, Gottschalk & Valente were found for the first time and a description is
      presented. A taxonomic dichotomous key with pictures is given for the
      Rhinoleucophenga species recorded in the Caatinga and Pampa biomes. The
      Neotropical open environments are areas of high diversity for Rhinoleucophenga.
      The description of new species and review of some older descriptions can change
      the area of species distribution and improve the faunistic knowledge of other
      localities in which previous studies have shown unidentified or misidentified
      Rhinoleucophenga species. 

PMID- 25947859
TI  - Taxonomy and biology of a new ambrosia gall midge Daphnephila urnicola sp. nov.
      (Diptera: Cecidomyiidae) inducing urn-shaped leaf galls on two species of
      Machilus (Lauraceae) in Taiwan.
AB  - Recent field surveys show that galls induced by Daphnephila spp. (Cecidomyiidae)
      on Machilus spp. (Lauraceae) are common in Taiwan, yet only five species, four
      leaf-gall inducers and one stem-gall inducer on M. thunbergii, have been named in
      the past. Here we describe a new species, Daphnephila urnicola sp. nov. Chiang,
      Yang & Tokuda, inducing urn-shaped galls on leaves of both M. zuihoensis and M.
      mushaensis. Comparisons of D. urnicola populations on M. zuihoensis and on M.
      mushaensis, indicate that they belong to one species, a result supported by gall
      midge morphology, life-history traits, gall shape and structure, the
      developmental process of gall tissues, fungal associations, and DNA-sequencing
      data. Size and structure of the gall operculum was found to differ between M.
      zuihoensis and M. mushahaensis. 

PMID- 25947860
TI  - New records of marine tardigrades from Moorea, French Polynesia, with the
      description of Styraconyx turbinarium sp. nov. (Arthrotardigrada,
      Halechiniscidae).
AB  - Five marine arthrotardigrade species are recorded from Moorea, Society Islands,
      French Polynesia. Four were collected from coral sand; two, Dipodarctus
      anaholiensis Pollock, 1995 and Florarctus kwoni Chang & Rho, 1997, are new
      records for the region, and two, Halechiniscus perfectus Schulz, 1955 and
      Styraconyx kristenseni kristenseni Renaud-Mornant, 1981, have been previously
      reported. The fifth, a new species Styraconyx turbinarium sp. nov., is described
      and was collected from the drifting brown alga Turbinaria ornata. The new species
      is characterized by the presence of peduncles on all digits, an elongate primary
      clava, and the lateral cirrus A arising from a common pedestal and enveloped by a
      common membrane extending almost to the claval tip. The new species differs from
      the most similar species, Styraconyx tyrrhenus D'Addabbo Gallo, Morone De Lucia &
      de Zio Grimaldi, 1989, by having longer and differently shaped primary clavae
      which are elongated in the new species and club-shaped in S. tyrrhenus. By having
      a dorsal cuticle that is coarsely punctated but without folds or other
      ornamentations, the new species can be easily distinguished from S. craticulus
      (Pollock, 1983), a species with similar primary clavae, but with cuticular dorsal
      folds ornamented with a grid-like pattern. 

PMID- 25947861
TI  - A new genus and species of micro bee flies from Brazil (Diptera: Mythicomyiidae:
      Psiloderoidinae).
AB  - A new genus of Mythicomyiidae, Amydrostylus triadicophallus gen. nov. et sp.
      nov., is described from the Chaco of Mato Grosso do Sul, Brazil. The type-series
      was collected by Malaise traps during the development of the SISBIOTA-Brasil
      project. Amydrostylus is closely related to the genus Acridophagus Evenhuis in
      the subfamily Psiloderoidinae, but it is distinguished by the minute apical
      stylus and the same length of br and bm cells. The species is described and
      illustrated in detail, including the male terminalia and female spermathecae.
      This is the first record of the subfamily Psiloderoidinae in South America. 

PMID- 25947862
TI  - Thiasophila szujeckii sp. n. (Coleoptera, Staphylinidae, Aleocharinae)--a cryptic
      species associated with Formica truncorum in Poland.
AB  - The article describes a new rove beetle species, Thiasophila szujeckii sp. n., in
      southeastern Poland. This new species is associated exclusively with Formica
      truncorum. The authors describe its sexual dimorphism of habitus, structure of
      antennae, eighth abdominal tergite and eighth sternite. T. szujeckii sp. n.
      shares most morphological features with T. angulata and T. lohsei known in
      Europe. Characters of adults which differentiate the new species from the above
      mentioned ones include body size, coloration, structure of ligula, aedeagus,
      parameres and spermatheca. In order to confirm morphological distinctivness of T.
      angulata and T. szujeckii, mitochondrial cytochrome oxidase II gene (COII)
      partial sequences of both taxa was analyzed. 

PMID- 25947863
TI  - Two new Craspedophorus species (Coleoptera: Carabidae: Panagaeini) from the
      Philippines.
AB  - Two new species of the genus Craspedophorus Hope, 1838 from the Philippine
      Islands namely, C.luzonensis sp. nov. and C. kirschenhoferi sp. nov. are
      described and their affinities are discussed, illustrated and compared with
      related taxa. Craspedophorus luzonensis sp. nov., from Luzon, belongs to the
      "obscurus species group, whereas C. kirschenhoferi sp. nov., from Mindanao,
      stands isolated in the genus. 

PMID- 25947864
TI  - New records of the genus Polysphincta Gravenhorst, 1829 (Hymenoptera:
      Ichneumonidae: Pimplinae) from the Oriental region.
AB  - A new species, Polysphincta punctigaster Varga & Reshchikov sp. n., the second
      known species of the genus from the Oriental region, is described from Thailand.
      Polysphincta asiatica Kusigemati, 1984 is considered to be a junior synonym of P.
      boops Tschek, 1869 (syn. nov.). Polysphincta longa Kasparyan, 1976 is recorded
      from the Oriental region for the first time. 

PMID- 25947865
TI  - Redescription of the adults and new descriptions of the previously unknown
      immature stages of Culex (Culex) articularis Philippi, 1865 (Diptera: Culicidae)
      from central Chile.
AB  - Male and female adults of Culex (Culex) articularis Philippi are redescribed, and
      the 4th-instar larva and pupa are described and illustrated for the first time.
      Culex articularis is compared with other species of the subgenus Culex.
      Illustrations of diagnostic characters of the female, male genitalia, 4th-instar
      larva, and pupa are also provided.

PMID- 25947866
TI  - Taxonomy of the genus Bolitogyrus Chevrolat (Coleoptera: Staphylinidae:
      Staphylinini: Quediina) from China with description of seven new species.
AB  - Seven new species of the genus Bolitogyrus Chevrolat, 1842 are described based on
      specimens collected in China, namely B. depressus sp. nov. from Guangdong, B.
      hainanensis sp. nov. and B. magnimaculosus sp. nov. from Hainan, B. metallicus
      sp. nov. from Hubei, and B. loculus sp. nov., B. profundus sp. nov. and B. uncus
      sp. nov. from Yunnan. The number of Bolitogyrus species is thus increased to 59.
      Line drawings and color illustrations of adults and genitalia of the new species
      and some others are given. A key to species known from China is provided, with
      the exception of B. fukienensis Scheerpeltz, 1974, which is only known from
      females. A geographical distribution map of all Chinese species is also compiled.

PMID- 25947867
TI  - First instar tibiotarsal chaetotaxy supports the Entomobryidae and Symphypleona
      (Collembola) forming a cluster in a phylogenetic tree.
AB  - Tibiotarsi, particularly their chaetotaxy, vary from species to orders in
      Collembola. Symphypleona, Poduromorpha and Isotomidae have been shown to possess
      characteristic patterns of tibiotarsal chaetotaxy, but the patterns in
      Entomobryoidea and Tomoceroidea, where a strong plurichaetosis is the rule,
      remains undocumented. The tibiotarsal chaetotaxy of first instars of 11 species
      of the main Entomobryidae subfamilies is described here for the first time. A
      basic pattern of five whorls with eight chaetae per whorl was found to occur in
      all examined species of Entomobryidae, with limited variations in the distal and
      proximal whorls. This pattern is similar to that of Symphypleona. Two hypotheses
      appear possible according to existing phylogenies, making it difficult to
      determine whether this obvious homology in tibiotarsal chaetotaxy is a
      plesiomorphy, which appeared independently in both superfamilies, or is a
      synapomorphy. We conclude that the primary chaetotaxy of tibiotarsus appears to
      be of high taxonomical value at suprafamilial but not at generic or tribal level.

PMID- 25947868
TI  - A revision of the genus Aphengium Harold, 1868 (Coleoptera: Scarabaeidae:
      Scarabaeinae: Ateuchini).
AB  - Aphengium Harold, a dung beetle genus endemic to the Atlantic forests of Brazil,
      comprises four valid species: A. sordidum Harold, 1868, A. cupreum Shipp, 1897,
      A. ibateguara sp. nov., A. curtum sp. nov.. In this revision of the genus each
      species is analyzed as follows: a detailed literature review, a diagnosis,
      illustrations of key morphological characters, a listing of material examined and
      geographic distribution. A lectotype is designated for A. sordidum, and a neotype
      for A. cupreum. 

PMID- 25947869
TI  - A review of the genus Miridiba Reitter (Coleoptera: Scarabaeidae: Melolonthinae)
      of Taiwan.
AB  - The six Miridiba Reitter, 1902 species, including Miridiba taoi Li & Wang, new
      species, Miridiba huesiotoi Li & Yang, new species, and Miridiba taipei Wang &
      Li, new species from Taiwan are reviewed. A key for the identification of adults
      is provided. The following information is provided for each species: literature
      review, synonyms, diagnoses, data of material used, description or redescription,
      illustrations, distributional data, and remarks. 

PMID- 25947870
TI  - Chaudhuriomyia, a new tanypod genus of Macropelopiini (Diptera: Chironomidae:
      Tanypodinae) from the Eastern Himalaya.
AB  - A new genus, Chaudhuriomyia in the tribe Macropelopiini belonging to subfamily
      Tanypodinae is described and illustrated in all life stages. The genus can be
      distinguished from all the other known Macropelopiini by the presence of a blunt
      claw on fore leg and a smooth surface of tibial spur in adult male, seminal
      capsules without proper neck in adult female, round anal lobe in pupa, and
      slightly inwardly bent inner tooth of ligula in larva. Generic diagnoses for
      larva, pupa and adult are provided. Taxonomic position and distribution of the
      genus are discussed along with a new adult key of tribe Macropelopiini. The
      specimens were collected from a stream in Indo-Bhutan border area of Eastern
      Himalaya in Indian Subcontinent. A note on the ecology and biology of the new
      genus is included. 

PMID- 25947871
TI  - Review of the genus Myrmozercon Berlese (Acari: Laelapidae), with description of
      a new species from Iran.
AB  - A new species of laelapid mite, Myrmozercon hunteri sp. nov. associated with
      Myrmica sp. (Hymenoptera: Formicidae), is described and illustrated. A key to 18
      species of Myrmozercon is presented. Ten further species, all described prior to
      1950, are briefly diagnosed but cannot be included in the key. Myrmozercon is
      shown to include a distinct group, Myrmozercon sensu stricto, which all have
      short, highly hypotrichous legs and a series of other consistent character
      states. This group probably arises from within Myrmozercon sensu lato, which have
      long legs with little or no hypotrichy, but some species also have character
      states found in Myrmozercon s.s. Myrmozercon ovatum Karawajew, 1909 is regarded a
      junior synonym of M. brevipes Berlese, 1902. 

PMID- 25947872
TI  - The genus Milnesium (Eutardigrada: Milnesiidae) in the Sierra Nevada de Santa
      Marta (Colombia), with the description of Milnesium kogui sp. nov.
AB  - A new species, Milnesium kogui sp. nov. is described from the Sierra Nevada de
      Santa Marta, Colombia. The new species belongs to the tardigradum group and is
      most similar, by the claw configuration [2-2]-[2-2], to Milnesium dujiangensis
      and Milnesium katarzynae. Milnesium kogui sp. nov. differs from M. dujiangensis
      mainly by the presence of primary branches on all legs and from M. katarzynae by
      the absence of dorsal sculpture. Additionally, in this paper we present a list of
      all Milnesium species recorded in Colombia including Milnesium cf. barbadosense
      Meyer & Hinton, 2012 and M. brachyungue Binda & Pilato, 1990, new additions to
      the recorded fauna of Colombia. 

PMID- 25947873
TI  - Bryozoans from rio grande do sul continental shelf, southern Brazil.
AB  - The continental shelf of Rio Grande do Sul (RS) is predominantly composed of
      unconsolidated sediments with a few hard substrates represented principally by
      beachrock. In this area there are elongate deposits of shell gravel material
      which are interpreted as indicators of the palaeo-shorelines. These Pleistocene
      deposits are overlapped by Holocene sediments (Recent), but are exposed during
      erosive events caused by extra-tropical cyclones, which provide the mixture of
      both sediments mainly during autumn and winter. The few studies on bryozoans made
      in this area previously recorded seven species, one fossil and the other six from
      Recent fluvial and marine environments. The aim of the present study was to
      describe the eight most abundant bryozoan species that occur in the inner RS
      shelf. Of these, four are new records for RS State (Arachnopusia aff. pusae,
      Hippomonavella brasiliensis, Turbicellepora pourtalesi, and Lifuella
      gorgonensis), and the other four are new to science (Chaperia taylori, Micropora
      nodimagna, Cellaria riograndensis, and Exochella moyani). 

PMID- 25947874
TI  - A new hermit crab (Anomura, Paguroidea) from the upper Albian (Cretaceous) of
      Annopol, Poland.
AB  - A new diogenid paguroid, Paguristes liwinskii sp. nov., is described from upper
      Albian phosphorite-bearing deposits near Annopol, along the east bank of the
      River Vistula (Wisla), east-central Poland. This new species constitutes an
      additional example of Early-Mid-Cretaceous macrofaunal shift, from marine reefal
      limestone to siliciclastic facies, triggered by the worldwide radiation of
      planktonic organisms. The species described here is the earliest known member of
      the genus Paguristes, previously recorded from the upper Santonian/lower
      Campanian to the Recent. 

PMID- 25947875
TI  - A bizarre new species of Triclistus Forster (Hymenoptera: Ichneumonidae;
      Metopiinae) from Amazonia.
AB  - A new bizarre new species of Metopiinae, Triclistus amazopeikkus sp. nov., is
      described and illustrated. The new species was collected from the lowland
      Peruvian Amazonia. 

PMID- 25947876
TI  - The gasteruptiid wasp fauna of New Caledonia, with description of three new
      species of Gasteruption (Hymenoptera: Evanioidea: Gasteruptiidae).
AB  - The rarely collected gasteruptiid wasp fauna (Evanioidea: Gasteruptiidae) of New
      Caledonia is reviewed. Previously only two species of Pseudofoenus
      (Hyptiogastrinae) were known. Here, we record the subfamily Gasteruptiinae from
      New Caledonia for the first time and describe three new species of Gasteruption:
      G. lacoulee Jennings, Krogmann & Parslow, sp. nov., G. maquis Jennings, Krogmann
      & Parslow, sp. nov., and G. sarramea Jennings, Krogmann & Parslow, sp. nov. An
      identification key to the Gasteruptiidae of New Caledonia is provided. 

PMID- 25947877
TI  - Rapid change in the ciprofloxacin resistance pattern among Neisseria gonorrhoeae
      strains in Nuuk, Greenland: time to reconsider preventive and treatment
      strategies.
AB  - OBJECTIVES: Sexually transmitted infections (STIs), including infections with
      Neisseria gonorrhoeae (GC), are highly incident in Greenland. Since January 2011,
      GC testing has been performed on urine with nucleic acid amplification tests
      (NAATs) by strand displacement amplification (Becton Dickinson ProbeTec).
      Monitoring of GC antibiotic susceptibility by culture was introduced in Nuuk in
      2012. Until 2014, no cases of ciprofloxacin-resistant GC strains were reported.
      In this paper, we report the finding of ciprofloxacin-resistant GC and describe
      the most recent incidence of GC infections in Greenland. METHODS: The number of
      urine NAATs and culture-positive swabs from January to October 2014 were obtained
      from the Central Laboratory at Queens Ingrid's Hospital in Nuuk and stratified on
      gender, place and period of testing. Incidence rates were estimated as number of
      urine NAAT * (12/10) per 100,000 inhabitants. Men in Nuuk with a positive NAAT
      for GC were encouraged to provide a urethral swab for culture and susceptibility
      testing. RESULTS: From January to October 2014, a total of 5,436 urine GC NAATs
      were performed on patients from Nuuk and 9,031 from the rest of Greenland. Of
      these, 422 (8%) and 820 (9%) were positive, respectively. From January to August,
      6 (15%) cultures from Nuuk were ciprofloxacin resistant while in September and
      October, 26 (59%) were ciprofloxacin resistant (p<0.01). In total, 35 (40%) of 88
      culture-positive isolates showed ciprofloxacin resistance. GC incidence in Nuuk
      was 3,017 per 100,000 inhabitants per year, compared to 2,491 per 100,000
      inhabitants per year in the rest of Greenland. CONCLUSION: Within a short period,
      a rapid and dramatic change in ciprofloxacin susceptibility among GC strains
      isolated in Nuuk was documented and recommendation for first line treatments has
      changed. Continued monitoring and rethinking of primary and secondary preventive
      initiatives is highly recommended in this high GC incidence setting.

PMID- 25947878
TI  - Malignant catarrhal fever in a Vietnamese pot-bellied pig. A potential threat to
      pigs in mixed-species exhibits?
AB  - Malignant catarrhal fever (MCF) represents a sporadic and often fatal disease in
      various ungulate species including rarely swine. A close contact between
      susceptible and reservoir species of ovine herpesvirus-2 (OvHV-2) is a
      requirement for virus transmission. As in ruminants, a rapid course of disease
      with lymphohistiocytic meningoencephalitis and necrotizing vasculitis in multiple
      organs is frequently seen in porcine MCF. This report describes a case of MCF in
      a Vietnamese pot-bellied pig, which was kept in a zoological exhibit with direct
      contact to various ruminants. It represents the first description of porcine MCF
      with proven natural OvHV-2 infection in Germany. OvHV-2 should be considered as
      cause of fatalities among swine especially in mixed-species exhibits as present
      in many zoological gardens. Also farm pigs kept in free ranging husbandry systems
      with potential contact to sheep and other ruminant species may be at risk. 

PMID- 25947880
TI  - Pocket-Sized Ultrasound for Physical Diagnosis.

PMID- 25947879
TI  - On the effects of leaflet microstructure and constitutive model on the closing
      behavior of the mitral valve.
AB  - Recent long-term studies showed an unsatisfactory recurrence rate of severe
      mitral regurgitation 3-5 years after surgical repair, suggesting that excessive
      tissue stresses and the resulting strain-induced tissue failure are potential
      etiological factors controlling the success of surgical repair for treating
      mitral valve (MV) diseases. We hypothesized that restoring normal MV tissue
      stresses in MV repair techniques would ultimately lead to improved repair
      durability through the restoration of MV normal homeostatic state. Therefore, we
      developed a micro- and macro- anatomically accurate MV finite element model by
      incorporating actual fiber microstructural architecture and a realistic structure
      based constitutive model. We investigated MV closing behaviors, with extensive in
      vitro data used for validating the proposed model. Comparative and parametric
      studies were conducted to identify essential model fidelity and information for
      achieving desirable accuracy. More importantly, for the first time, the
      interrelationship between the local fiber ensemble behavior and the organ-level
      MV closing behavior was investigated using a computational simulation. These
      novel results indicated not only the appropriate parameter ranges, but also the
      importance of the microstructural tuning (i.e., straightening and re-orientation)
      of the collagen/elastin fiber networks at the macroscopic tissue level for
      facilitating the proper coaptation and natural functioning of the MV apparatus
      under physiological loading at the organ level. The proposed computational model
      would serve as a logical first step toward our long-term modeling goal
      facilitating simulation-guided design of optimal surgical repair strategies for
      treating diseased MVs with significantly enhanced durability. 

PMID- 25947881
TI  - Impact of an Intervention to Improve Weekend Hospital Care at an Academic Medical
      Center: An Observational Study.
AB  - BACKGROUND: Hospital care on weekends has been associated with delays in care,
      reduced quality, and poor clinical outcomes. OBJECTIVE: The purpose of this study
      was to evaluate the impact of a weekend hospital intervention on processes of
      care and clinical outcomes. The multifaceted intervention included expanded
      weekend diagnostic services, improved weekend discharge processes, and increased
      physician and care management services on weekends. DESIGN AND PATIENTS: This was
      an interrupted time series observational study of adult non-obstetric patients
      hospitalized at a single academic medical center between January 2011 and January
      2014. The study included 18 months prior to and 19 months following the
      implementation of the intervention. Data were analyzed using segmented regression
      analysis with adjustment for confounders. MAIN MEASURES: The primary outcome was
      average length of stay. Secondary outcomes included percent of patients
      discharged on weekends, 30-day readmission rate, and in-hospital mortality rate.
      KEY RESULTS: The study included 57,163 hospitalizations. Following implementation
      of the intervention, average length of stay decreased by 13 % (95 % CI 10-15 %)
      and continued to decrease by 1 % (95 % CI 1-2 %) per month as compared to the
      underlying time trend. The proportion of weekend discharges increased by 12 % (95
      % CI 2-22 %) at the time of the intervention and continued to increase by 2 % (95
      % CI 1-3 %) per month thereafter. The intervention had no impact on readmissions
      or mortality. During the post-implementation period, the hospital was evacuated
      and closed for 2 months due to damage from Hurricane Sandy, and a new hospital
      wide electronic health record was introduced. The contributions of these events
      to our findings are not known. We observed a lower inpatient census and found
      differences in patient characteristics, including higher rates of Medicaid
      insurance and comorbidities, in the post-Hurricane Sandy period as compared to
      the pre-Sandy period. CONCLUSIONS: The intervention was associated with a
      reduction in length of stay and an increase in weekend discharges. Our
      longitudinal study also illuminated the challenges of evaluating the
      effectiveness of a large-scale intervention in a real-world hospital setting.

PMID- 25947883
TI  - Clinical Benefit of American College of Chest Physicians Versus European Society
      of Cardiology Guidelines for Stroke Prophylaxis in Atrial Fibrillation.

PMID- 25947882
TI  - The Effect of Cigarette Smoking on Diabetic Peripheral Neuropathy: A Systematic
      Review and Meta-Analysis.
AB  - OBJECTIVE: Studies suggest that smoking may be a risk factor for the development
      of microvascular complications such as diabetic peripheral neuropathy (DPN). The
      objective of this study was to assess the relationship between smoking and DPN in
      persons with type 1 or type 2 diabetes. RESEARCH DESIGN AND METHODS: A systematic
      review of the PubMed, Embase, and Cochrane clinical trials databases was
      conducted for the period from January 1966 to November 2014 for cohort, cross
      sectional and case-control studies that assessed the relationship between smoking
      and DPN. Separate meta-analyses for prospective cohort studies and case-control
      or cross-sectional studies were performed using random effects models. RESULTS:
      Thirty-eight studies (10 prospective cohort and 28 cross-sectional) were
      included. The prospective cohort studies included 5558 participants without DPN
      at baseline. During follow-up ranging from 2 to 10 years, 1550 cases of DPN
      occurred. The pooled unadjusted odds ratio (OR) of developing DPN associated with
      smoking was 1.26 (95% CI 0.86-1.85; I(2) = 74%; evidence grade: low strength).
      Stratified analyses of the prospective studies revealed that studies of higher
      quality and with better levels of adjustment and longer follow-up showed a
      significant positive association between smoking and DPN, with less
      heterogeneity. The cross-sectional studies included 27,594 participants. The
      pooled OR of DPN associated with smoking was 1.42 (95% CI 1.21-1.65; I(2) = 65%;
      evidence grade: low strength). There was no evidence of publication bias.
      CONCLUSIONS: Smoking may be associated with an increased risk of DPN in persons
      with diabetes. Further studies are needed to test whether this association is
      causal and whether smoking cessation reduces the risk of DPN in adults with
      diabetes.

PMID- 25947884
TI  - Facile synthesis of 4- and 7-azaindoles from the corresponding imines by
      palladium-catalyzed cascade C-C and C-N coupling.
AB  - The cyclization of 2,3-dihalopyridines with readily available imines provides a
      convenient and regioselective approach to 4- and 7-azaindoles. The
      regioselectivity can be controlled by the choice of the halogen atoms at the
      pyridine ring (chlorine versus bromine). 

PMID- 25947885
TI  - Optimizing outcome reporting after radical cystectomy for organ-confined
      urothelial carcinoma of the bladder using oncological trifecta and pentafecta.
AB  - Radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) is
      associated with heterogeneous functional and oncological outcomes. The aim of
      this study was to generate trifecta and pentafecta criteria to optimize outcome
      reporting after RC. METHODS: We interviewed 50 experts to consider a virtual
      group of patients (age <= 75 years, ASA score <= 3) undergoing RC for a cT2 UCB
      and a final histology of <=pT3pN0M0. A ranking was generated for the three and
      five criteria with the highest sum score. The criteria were applied to the
      Prospective Multicenter Radical Cystectomy Series 2011. Multivariable binary
      logistic regression analyses were used to evaluate the impact of clinical and
      histopathological parameters on meeting the top selected criteria. RESULTS: The
      criteria with the highest sum score were negative soft tissue surgical margin,
      lymph node (LN) dissection of at least 16 LNs, no complications according to
      Clavien-Dindo grade 3-5 within 90 days after RC, treatment-free time between TUR
      BT with detection of muscle-invasive UCB and RC <3 months and the absence of
      local UCB-recurrence in the pelvis <=12 months. The first three criteria formed
      trifecta, and all five criteria pentafecta. A total of 334 patients qualified for
      final analysis, whereas 35.3 and 29 % met trifecta and pentafecta criteria,
      respectively. Multivariable analyses showed that the relative probability of
      meeting trifecta and pentafecta decreases with higher age (3.2 %, p = 0.043 and
      3.3 %, p = 0.042) per year, respectively. CONCLUSIONS: Trifecta and pentafecta
      incorporate essential criteria in terms of outcome reporting and might be
      considered for the improvement of standardized quality assessment after RC for
      UCB.

PMID- 25947887
TI  - Improvement of bacterial clearance and relief of clinical signs of Salmonella
      enterica serovar Typhimurium infection in pigs through upregulation of Th 1
      specific responses by administration of a combination of two silicate minerals,
      biotite and bentonite.
AB  - Biotite and bentonite are phyllosilicate minerals that were originally used in
      industrial applications. Several beneficial activities of them have recently been
      reported, especially regulation of the immune system and antimicrobial effects.
      Therefore, we investigated the immune-enhancing and bacterial clearance effects
      of a biotite and bentonite mixture (BBM) on experimental infection of Salmonella
      enterica serovar Typhimurium (S. Typhimurium) to determine whether the BBM could
      be used as an alternative antibiotic. We administered 1% or 2% BBM as a feed
      supplement. We then evaluated the bacterial clearance effects of the BBM against
      S. Typhimurium. We also evaluated the immune-enhancing effect of the BBM through
      several immunological experiments that included examination of the lysozyme
      activity, CD4(+)/CD8(+) T lymphocyte ratio and the T-helper type 1 (Th 1)
      cytokine profile. The clinical signs of S. Typhimurium and the number of viable
      bacteria in feces and tissues were significantly decreased in both BBM groups,
      especially in the 2% BBM group. The BBM also markedly enhanced the lysozyme
      activity, CD4(+)/CD8(+) T lymphocyte ratio and expression levels of IFN-gamma and
      IL-12 in S. Typhimurium-challenged pigs. Therefore, the BBM could be a good
      candidate as an alternative antibiotic that improves Th 1-specific immune
      responses and the bacterial clearance effect.

PMID- 25947888
TI  - Endostatin inhibits T-type Ca2+ channel current in guinea pig ventricular
      myocyte.
AB  - Endostatin, a fragment of collagen XVIII, is known as an endogenous angiogenesis
      inhibitor, and its serum concentration increases in various cardiovascular
      diseases. T-type Ca(2+) channel, low voltage-activated Ca(2+) channel, is not
      expressed in adult ventricular myocytes. Re-expression of T-type Ca(2+) channels
      in cardiac myocytes is thought to be involved in the development of cardiac
      hypertrophy. We examined the effects of endostatin on T-type Ca(2+) channel
      current by whole-cell patch clamp technique in freshly isolated adult guinea pig
      ventricular myocytes, which exceptionally express T-type Ca(2+) channels.
      Although endostatin 300 ng/ml had no effect on L-type Ca(2+) current, it
      significantly inhibited T-type Ca(2+) current. These data indicate that
      endostatin can be an endogenous inhibitor of T-type Ca(2+) channels in the
      cardiac myocytes. 

PMID- 25947889
TI  - 'Sepsis-related anemia' is absent at hospital presentation; a retrospective
      cohort analysis.
AB  - BACKGROUND: Anemia is a common feature during sepsis that occurs due to
      iatrogenic blood loss, depression of serum iron levels and erythropoietin
      production, and a decreased lifespan of erythrocytes. However, these mechanisms
      are unlikely to play a role in anemia at the start of sepsis. Moreover,
      sequestration of fluids, renal failure and increase of intravascular space may
      additionally influence the change in hemoglobin concentration during intravenous
      fluid administration in the acute phase of sepsis. METHODS: In this retrospective
      study, patients who were admitted acutely to the Intensive Care Unit (ICU) were
      included. Patients who fulfilled the international criteria for severe sepsis or
      septic shock were included in the sepsis group (S-group). The remaining patients
      were allocated to the control group (C-group). Laboratory data from blood samples
      taken at first presentation to the hospital and at admission to the ICU, the
      amount of intravenous fluid administration and length of stay in the emergency
      department were collected and tested for significant differences between groups.
      RESULTS: The difference in hemoglobin concentration between the S-group (n = 296)
      and C-group (n = 320) at first presentation in hospital was not significant (8.8
      +/- 1.2 versus 8.9 +/- 1.2 mmol/l, respectively, p = 0.07). The reduction in
      hemoglobin concentration from the first presentation at the emergency department
      to ICU admission was significantly greater in the S-group compared to the C-group
      (1 [0.5-1.7] versus 0.5 [0.1-1.1] mmol/l, (p < 0.001)). Spearman rho correlation
      coefficients between the reduction in hemoglobin concentration and the amount of
      intravenous fluids administered or the creatinine level in the emergency
      department were significant (0.3 and 0.4, respectively, p < 0.001). In a
      multivariate regression analysis, creatinine, the amount of fluid administration
      and the presence of sepsis remained independently associated. CONCLUSIONS: Prior
      to in-hospital intravenous fluid administration, there is no significant
      difference in hemoglobin concentration between acute septic patients and acutely
      ill controls. Within several hours after hospital admission, there is a
      significant reduction in hemoglobin concentration, not only associated with the
      amount of intravenous fluids administered and the creatinine level, but also
      independently with sepsis itself.

PMID- 25947891
TI  - Higher SOD1 Gene Expression in Cumulus Cells From Infertile Women With Moderate
      and Severe Endometriosis.
AB  - It is questioned whether worsening of oocyte quality and oxidative stress (OS)
      are involved in the pathogenesis of infertility related to endometriosis and in
      compromised intracytoplasmic sperm injection (ICSI) outcomes. Cumulus cells (CCs)
      protect oocytes from entering apoptosis induced by OS. Thus, we carried out a
      case-control study comparing expression of superoxide dismutase 1 (SOD1),
      superoxide dismutase 2 (SOD2), and glutathione peroxidase 4 (GPX4; genes encoding
      for the main antioxidant enzymes) in CCs from mature oocytes of 26 infertile
      patients with minimal/mild endometriosis, 14 patients with moderate/severe
      endometriosis, and 41 controls undergoing controlled ovarian stimulation for
      ICSI, using real-time polymerase chain reaction. As a secondary objective, we
      investigated the interaction between the expression of these genes and clinical
      pregnancy (CP) by a statistical model. Only infertile women with moderate/severe
      endometriosis showed increased expression of the SOD1 in CCs compared to women
      with minimal/mild endometriosis and controls, with a positive interaction between
      increased expression and the occurrence of CP, suggesting that SOD1 might be a
      potential biomarker of CP following ICSI. 

PMID- 25947890
TI  - Gastrointestinal metastasis from primary sarcomatoid carcinoma of the lung: a
      case report and review of the literature.
AB  - Gastrointestinal metastases in lung cancer are extremely rare. The report
      presents a rare case of primary lung sarcomatoid carcinoma with both gastric and
      colonic metastases, and reviews the literature about endoscopic presentation of
      colonic metastases. 

PMID- 25947892
TI  - GDM Alters Expression of Placental Estrogen Receptor alpha in a Cell Type and
      Gender-Specific Manner.
AB  - OBJECTIVE: The nuclear receptor estrogen receptor alpha (ERalpha) is one of the
      key players in energy balance, insulin resistance, and trophoblast
      differentiation. We tested the hypothesis that gestational diabetes mellitus
      (GDM) alters expression of placental ERalpha in a cell type-specific manner and
      that this regulation may involve epigenetic changes. STUDY DESIGN: Expression of
      ERalpha was analyzed by immunohistochemistry using the semiquantitative
      immunoreactive score in 80 placentas (40 GDM/40 controls). Quantitative real-time
      polymerase chain reaction (PCR) measured ERalpha messenger RNA (mRNA) in decidual
      tissue. Methylation-specific PCR was performed to analyze cytosine-phosphatidyl
      guanine-island methylation of the ERalpha promoter. RESULTS: Expression of
      ERalpha protein is upregulated (P = .011) in GDM in extravillous trophoblasts but
      not in syncytiotrophoblast. Gestational diabetes mellitus downregulated ERalpha
      in decidual vessels only in pregnancies with male but not female fetuses.
      Furthermore, mRNA of the ERalpha encoding gene estrogen receptor gene 1 (ESR1)
      was increased (+1.77 fold) in GDM decidua when compared to controls (P = .024).
      In parallel, the promoter of ESR1 was methylated only in decidua of healthy
      control individuals but not in GDM. CONCLUSION: Gestational diabetes mellitus
      affects expression of placental ERalpha in a cell type-dependent way, on
      epigenetic level. These data link GDM with epigenetic deregulations of ERalpha
      expression and open new insights into the intrauterine programming hypothesis of
      GDM.

PMID- 25947894
TI  - Characteristics of a cyclonic eddy and its influence on mesozooplankton community
      in the northern Bay of Bengal during early winter monsoon.
AB  - Characteristics of a cold-core eddy and its influence on the mesozooplankton
      community were studied along the central (87 degrees  E) Bay of Bengal during
      winter monsoon (November 2008) based on in situ data. The thermo-haline structure
      and the satellite-derived sea level anomaly maps showed the presence of a
      cyclonic eddy between 16 degrees  N and 20 degrees  N. The nutrient enhancement
      due to the eddy pumping in the euphotic column (~ 50 m) had resulted in high
      chlorophyll a concentration, a factor of 8 times higher than that outside the
      eddy, which led to higher mesozooplankton biovolume (0.35 +/- 0.36 ml m(-3)) and
      abundance (276 +/- 184 ind m(-3)). The northern cyclonic eddy (NCE) seems to
      exist for approximately 6 months between July and January. During summer, the NCE
      is forced by local wind stress curl and the resultant Ekman pumping, whereas
      during fall and early phase of the winter, it is sustained by westward
      propagating semi-annual Rossby waves. The longer existence of NCE in the study
      region, which originated 6 months prior to the present observation, provides a
      favourable environment for the mesozooplankton community to grow and reproduce,
      resulting in noticeable increase in the biovolume. Hence, the persistent and
      longer existence of NCE significantly influences the biological production of the
      generally oligotrophic BoB, making it locally biologically 'active'.

PMID- 25947893
TI  - Human-use antibacterial residues in the natural environment of China: implication
      for ecopharmacovigilance.
AB  - Antibacterial residues in the natural environment have been of increasing concern
      due to their impact on bacteria resistance development and toxicity to natural
      communities and ultimately to public health. China is a large country with high
      production and consumption of antibacterials for its population growth and
      economic development in recent years. In this article, we summarized the current
      situation of human-use antibacterial pollution in Chinese water (wastewaters,
      natural and drinking waters) and solid matrices (sludge, sediment, and soil)
      reported in 33 peer-reviewed papers. We found that, although there are adequate
      wastewater treatment systems in China, human-use antibacterial residues in the
      natural environment were reported almost throughout the whole country. Three most
      frequently prescribed classes of antibacterials in China, including quinolones,
      macrolides, and beta-lactam, were also the predominant classes of residues in
      Chinese environment, manifested as the high concentration and detection
      frequency. In view of this alarming situation, we have presented that
      ecopharmacovigilance (EPV) might be implemented in the antibacterial drug
      administration of China, as the active participation of the pharmaceutical
      industry and drug regulatory authorities from the diffuse source of antibacterial
      pollution. Considering EPV experience of developed countries together with the
      actual conditions of China, we have identified some approaches that can be taken,
      including:* Focus on education;* Further strengthening and persevering the
      antibacterial stewardship strategies and pharmaceutical take-back programs in
      China;* Designing greener antibacterials with better degradability in the
      environment;* Implementing environmental risk assessment prior to launch of new
      drugs;* Strengthening collaboration in EPV-related areas. 

PMID- 25947895
TI  - A comparative study on carbon footprint of rice production between household and
      aggregated farms from Jiangxi, China.
AB  - Quantifying the carbon footprint (CF) for crop production can help identify key
      options to mitigate greenhouse gas (GHG) emissions in agriculture. In the present
      study, both household and aggregated farm scales were surveyed to obtain the data
      of rice production and farming management practices in a typical rice cultivation
      area of Northern Jiangxi, China. The CFs of the different rice systems including
      early rice, late rice, and single rice under household and aggregated farm scale
      were calculated. In general, early rice had the lower CF in terms of land use and
      grain production being 4.54 +/- 0.44 t CO2-eq./ha and 0.62 +/- 0.1 t CO2-eq./t
      grain than single rice (6.84 +/- 0.79 t CO2-eq./ha and 0.80 +/- 0.13 t CO2-eq./t
      grain) and late rice (8.72 +/- 0.54 t CO2-eq./ha and 1.1 +/- 0.17 t CO2-eq./t
      grain). The emissions from nitrogen fertilizer use accounted for 33 % of the
      total CF on average and the direct CH4 emissions for 57 %. The results indicated
      that the CF of double rice cropping under aggregated farm being 0.86 +/- 0.11 t
      CO2-eq./t grain was lower by 25 % than that being 1.14 +/- 0.25 t CO2-eq./t grain
      under household farm, mainly due to high nitrogen use efficiency and low methane
      emissions. Therefore, developing the aggregated farm scale with efficient use of
      agro-chemicals and farming operation for greater profitability could offer a
      strategy for reducing GHG emissions in China's agriculture.

PMID- 25947896
TI  - Individual differences in cognitive control processes and their relationship to
      emotion regulation.
AB  - Cognitive control and emotional control share many similarities, but the specific
      relationship between these processes is not well understood. This study explored
      the relationship between three types of cognitive control (working memory
      updating, response inhibition and set-shifting) and two emotional regulation
      strategies (expressive suppression and cognitive reappraisal). Corrugator
      electromyography, behaviour and self-reports of affect were measured as indices
      of emotion regulation. Results indicate that working memory updating predicted
      negative affect reduction during reappraisal and during expressive suppression.
      This study specifically shows that the working memory component of cognitive
      control is associated with negative affect reduction. Response inhibition and set
      shifting were not specifically related to negative affect reduction, but these
      variables did predict aspects of emotional behaviour and regulation. These
      results suggest a general role for cognitive control in some aspects of emotion
      regulation as well as a specific modulatory role for working memory updating in
      the regulation of negative affect. 

PMID- 25947897
TI  - Impact and alternative metrics for medical publishing: our experience with
      International Orthopaedics.
AB  - PURPOSE: This paper compares the traditional tools of calculation for a journal's
      efficacy and visibility with the new tools that have arrived from the Internet,
      social media and search engines. The examples concern publications of orthopaedic
      surgery and in particular International Orthopaedics. METHODS AND RESULTS: Until
      recently, the prestige of publications, authors or journals was evaluated by the
      number of citations using the traditional citation metrics, most commonly the
      impact factor. Over the last few years, scientific medical literature has
      developed exponentially. The Internet has dramatically changed the way of sharing
      and the speed of flow of medical information. New tools have allowed readers from
      all over the world to access information and record their experience. Web
      platforms such as Facebook(r) and Twitter(r) have allowed for inputs from the
      general public. Professional sites such as LinkedIn(r) and more specialised sites
      such as ResearchGate(r), BioMed Central(r) and OrthoEvidence(r) have provided
      specific information on defined fields of science. Scientific and professional
      blogs provide free access quality information. Therefore, in this new era of
      advanced wireless technology and online medical communication, the prestige of a
      paper should also be evaluated by alternative metrics (altmetrics) that measure
      the visibility of the scientific information by collecting Internet citations,
      number of downloads, number of hits on the Internet, number of tweets and likes
      of scholarly articles by newspapers, blogs, social media and other sources of
      data. CONCLUSIONS AND DISCUSSION: This article provides insights into altmetrics
      and informs the reader about current tools for optimal visibility and citation of
      their work. It also includes useful information about the performance of
      International Orthopaedics and the bias between traditional publication metrics
      and the new alternatives.

PMID- 25947898
TI  - Accuracy of combined anteversion in image-free navigated total hip arthroplasty:
      stem-first or cup-first technique?
AB  - PURPOSE: In total hip arthroplasty (THA), combined anteversion (CA) is used as a
      parameter for assessment of overall prosthetic alignment. The purpose of this
      study was to comparatively examine the CA value in patients who underwent primary
      THA using the image-free navigation system either with a cup-first or stem-first
      technique. METHODS: Eighty-three hips undergoing primary THA using the
      OrthoPilot(r) image-free navigation system (B. Braun-Aesculap, Tuttlingen,
      Germany) were included in this study. The patient population was divided into two
      groups depending on the procedure used: cup-first technique and stem-first
      technique. In the cup-first group, inclination and anteversion (AV) angles were
      targeted at 35-45 degrees  and 15-25 degrees , respectively, while stem
      antetorsion (AT) was determined for each patient based on the amount of
      individual native femoral AT angle. In the stem-first group, the femur was
      prepared first with the target angle corresponding to the native femoral AT and
      the cup AV was decided considering the CA calculated with Widmer's formula
      (aiming at the optimal Widmer's CA of 37.3 degrees ). RESULTS: Better consistency
      in Widmer's CA values was attained in the stem-first group as indicated by the
      smaller SD values. In the assessment of overall alignment, Widmer's CA values
      were within the satisfactory range (37 +/- 5 degrees ) in 41.9 and 92.3 % of the
      subjects in the cup-first group and the stem-first group, respectively.
      CONCLUSIONS: The stem-first technique with image-free navigated THA could
      effectively achieve accurate and consistent control of the CA value and thus is
      expected to improve the surgical outcome.

PMID- 25947899
TI  - Bicortical screw fixation provides superior biomechanical stability but
      devastating failure modes in periprosthetic femur fracture care using locking
      plates.
AB  - PURPOSE: The incidence of periprosthetic fractures is inevitably increasing.
      Sufficient stabilisation and proper screw placement next to large-volume implants
      remains difficult. Modern locking plates allow polyaxial, thus bicortical, screw
      placement around a prosthetic stem. This study analysed the biomechanical
      properties of different screw configurations in a locking plate construct of a
      periprosthetic femoral fracture model. METHODS: A total of 20 Sawbones were used
      to stabilise a Vancouver-B1 femoral fracture with a locking plate using either
      four monocortical screws or three bicortical screws for proximal fixation. These
      were loaded with an increasing axial compression until failure. RESULTS:
      Bicortical screw purchase was significantly superior to monocortical regarding
      load to failure (1,510 N +/- 284 N versus 2,350 N +/- 212 N, p < 0.001) and
      maximal number of cycles (6803 +/- 760 versus 4041 +/- 923, p < 0.001). However,
      the mode of failure in the bicortical group was a severe comminuted fracture
      pattern as opposed to the monocortical group in which a pull-out of the screws
      without further damage to the bone was observed. CONCLUSIONS: Bicortical screw
      placement enhances the primary stability in treating periprosthetic femoral
      fractures. Notably, the mode of failure may limit the salvage options in case of
      revision surgery.

PMID- 25947900
TI  - Driving and emergency braking may be impaired after tibiotalar joint arthrodesis:
      conclusions after a case series.
AB  - PURPOSE: To assess whether reaction time (RT) and movement time (MT), as the two
      components of the total brake response time (TBRT) and brake force (BF) are
      different in patients with a foot joint arthrodesis in comparison to controls.
      METHODS: The study was a comparative case series in a driving simulator under
      realistic driving conditions. Mobile patients without a walker, >=6 months after
      surgery who were driving a car and had no neurological co-morbidity, knee or hip
      joint prosthesis were included in the study. The selection criteria resulted in
      12 patients with right tibiotalar joint arthrodesis (TTJA) and 12 patients with
      another right foot joint arthrodesis (OFJA), who were compared to 17 individuals
      without any ankle-joint pathology. For TBRT, an empirical safe driving threshold
      of 700 ms was used. The outcome measures were RT, MT, TBRT, BF and McGuire score.
      RESULTS: MT (p = 0.034) and TBRT (p = 0.026) were longer in TTJA patients in
      comparison with the controls. Also, more patients with TTJA than patients with
      OFJA and controls exceeded the safe driving threshold (p = 0.028). The outcomes
      in OFJA patients and in controls were comparable. The McGuire score was similar
      between the TTJA and OFJA patients (p = 0.26). CONCLUSIONS: Significantly slower
      MT and TBRT, and significantly more patients exceeding the safe driving
      threshold, were observed after a tibiotalar-joint arthrodesis in comparison to
      the controls. Patients with OFJAs were not significantly different from the
      controls. Driving and emergency braking may be impaired after tibiotalar-joint
      arthrodesis.

PMID- 25947901
TI  - Computer-assisted total knee replacement after medial opening wedge high tibial
      osteotomy: medium-term results in a series of ninety cases.
AB  - PURPOSE: The aim of this study was to evaluate the medium-term results of total
      knee replacements (TKRs) after medial opening wedge valgising tibial osteotomy to
      those of primary TKR (TKR1). The hypothesis being that there would be no
      difference in results between these groups. METHODS: Series 1 was made up of 45
      TKRs after medial opening wedge high tibial osteotomy (MHTO)-30 men and ten women
      at an average age of 69 +/- seven years (54-82). This was compared to a second
      series of TKR1s-30 men and ten women at an average age of 69 +/- seven years (55
      78). The average IKS scores were 91 +/- 22.5 points (42-129) and 86 +/- 18 points
      (38-116) in the two groups respectively. The average pre-operative HKA angle was
      179 +/- 5 degrees  (169-193 degrees ) in group 1, and 173 +/- 7.5 degrees  (161
      193 degrees ) in group 2. Tibial mechanical axes were 90.5 +/- 4 degrees  (of
      which 24 knees had a valgus angle) and 85.05 +/- 3.5 degrees  (79-93 degrees ) in
      the two groups respectively. RESULTS: All patients were reviewed at an average
      follow-up of 47 +/- 24.5 months for series 1 and 185 +/- 8.5 months for series 2.
      The average IKS score was 184 +/- 6 for series 1 (172-200) and 185 +/- 8.5 (163
      200) for series 2 (p = 0.872). Thirty-seven patients in series 1 and 38 patients
      in series 2 were either extremely satisfied or satisfied with the intervention.
      The average post-operative HKA angle was 180.5 +/- 2.5 degrees  and 181 +/- 2
      degrees  (p = 0.122) and the average tibial mechanical axis was 89 +/- 1.5
      degrees  against 90 +/- 1 degrees  (p = 0.001). The results of the 24 knees with
      a valgus tibial mechanical axis were statistically no different. CONCLUSIONS:
      TKRs post medial opening wedge high tibial osteotomy have identical results to
      primary TKRs even in knees with a valgus tibial mechanical axis.

PMID- 25947902
TI  - Revision surgery after third generation autologous chondrocyte implantation in
      the knee.
AB  - PURPOSE: Third generation autologous chondrocyte implantation (ACI) is an
      established treatment for full thickness cartilage defects in the knee joint.
      However, little is known about cases when revision surgery is needed. The aim of
      the present study is to investigate the complication rates and the main reasons
      for revision surgery after third generation autologous chondrocyte implantation
      in the knee joint. It is of particular interest to examine in which cases
      revision surgery is needed and in which cases a "wait and see" strategy should be
      used. METHODS: A total of 143 consecutive patients with 171 cartilage defects
      were included in this study with a minimum follow-up of two years. All defects
      were treated with third generation ACI (NOVACART(r)3D). Clinical evaluation was
      carried out after six months, followed by an annual evaluation using the
      International Knee Documentation Committee (IKDC) subjective score and the visual
      analogue scale (VAS) for rest and during activity. Revision surgery was
      documented. RESULTS: The revision rate was 23.4 % (n = 36). The following major
      reasons for revision surgery were found in our study: symptomatic bone marrow
      edema (8.3 %, n = 3), arthrofibrosis (22.2 %, n = 8) and partial graft cartilage
      deficiency (47.2 %, n = 17). The following revision surgery was performed:
      retrograde drilling combined with Iloprost infusion therapy for bone marrow
      oedema (8.4 %, n = 3), arthroscopic arthrolysis of the suprapatellar recess (22.2
      %, n = 8) and microfracturing/antegrade drilling (47.3 %, n = 17). Significant
      improvements of clinical scores after revision surgery were observed. CONCLUSION:
      Revision surgery after third generation autologous chondrocyte implantation is
      common and is needed primarily in cases with arthrofibrosis, partial graft
      cartilage deficiency and symptomatic bone marrow oedema resulting in a
      significantly better clinical outcome.

PMID- 25947903
TI  - The split anterior tibialis tendon transfer procedure for spastic equinovarus
      foot in children with cerebral palsy: results and factors associated with a
      failed outcome.
AB  - PURPOSE: The aims of the study were to evaluate the outcomes and predictive
      factors of the split anterior tibialis tendon transfer (SPLATT) procedure for the
      treatment of the spastic equinovarus deformity in children with cerebral palsy
      (CCP). METHODS: Forty-five ambulatory CCP with 68 equinovarus feet, positive for
      the flexor withdrawal reflex test, aged 8.1 +/- 2.5 (range four to 15) years were
      enrolled. All feet underwent a soft tissue release procedure combined with the
      SPLATT procedure and were followed for at least 12 months after surgery. The
      functional outcome was rated using the criteria of Kling and co-workers. Pre
      treatment gross motor functional classification system (GMFCS) levels were
      compared to the patients' latest evaluations. Factors associated with outcomes
      and success rate were assessed. RESULTS: At an average follow-up of 5.5 +/- 3.3
      (range 1.1-16) years, feet were rated as excellent in 48 cases (70 %), good in
      ten (15 %) and poor in ten (15 %), respectively. Thirty-four CCP showed an
      improvement for the GMFCS level, P < 0.001. The factor that could predict a poor
      outcome was the pre-treatment GMFCS levels 3-4 with an odds ratio (95 % CI) of
      4.92 (0.96-25.2), P = 0.03. The ten years success rate of the SPLATT procedure
      between CCP with GMFCS levels 1-2 and levels 3-4 were not different with a mean
      +/- SD (95 % CI) of 0.85 +/- 0.1 (0.5-0.96) versus 0.6 +/- 0.1 (0.3-0.8), P =
      0.08, respectively. CONCLUSIONS: The SPLATT procedure provides a balanced
      function of the foot, thus improving the ambulatory ability in CCP and should be
      integrated into the surgical plan. Pre-treatment GMFCS levels 3-4 predicted
      unfavourable outcomes and should be addressed during pre-operative parental
      counselling.

PMID- 25947904
TI  - Arthroplasty for unstable pertrochanteric hip fractures may offer a lower re
      operation rate as compared to cephalomedullary nailing.
AB  - PURPOSE: Cephalomedullary (CM) nailing is widely used for the treatment of
      pertrochanteric hip fractures. Fixation failures with CM nailing tend to occur in
      unstable fracture patterns often necessitating revision surgery. The purpose of
      this study was to compare the complications and clinical outcomes of primary
      arthroplasty to CM nailing for the treatment of unstable pertrochanteric hip
      fractures. METHODS: We conducted an age-, sex-, and fracture type-matched case
      controlled study and identified 29 patients who underwent hip arthroplasty for an
      unstable pertrochanteric fracture (AO/OTA classification type 31A2.2/3 and 31.A3)
      at our institution. Their outcome was compared to a matched control group of 29
      patients treated with a CM nail. RESULTS: There was one major complication in the
      arthroplasty group (3.4 %), whereas there were six major complications in the
      nailing group (20.7 %) (P = 0.04). We found no significant difference between the
      groups with regards to blood loss, operative time, hospitalization time and the
      number of patients discharged to rehabilitation. Clinical outcome measured with
      Oxford hip score and SF-12 at the time of final follow-up was not significantly
      different between the groups. CONCLUSIONS: Arthroplasty is a viable option for
      treatment of unstable pertrochanteric fractures in an elderly population.
      Arthroplasty may offer a lower re-operation rate in the treatment of unstable
      pertrochanteric hip fractures as compared to CM nailing.

PMID- 25947906
TI  - Physical inactivity is associated with narrower lumbar intervertebral discs, high
      fat content of paraspinal muscles and low back pain and disability.
AB  - INTRODUCTION: Although physical inactivity has been associated with numerous
      chronic musculoskeletal complaints, few studies have examined its associations
      with spinal structures. Moreover, previously reported associations between
      physical activity and low back pain are conflicting. This study examined the
      associations between physical inactivity and intervertebral disc height,
      paraspinal fat content and low back pain and disability. METHODS: Seventy-two
      community-based volunteers not selected for low back pain underwent magnetic
      resonance imaging (MRI) of their lumbosacral spine (L1 to S1) between 2011 and
      2012. Physical activity was assessed between 2005 and 2008 by questionnaire,
      while low back pain and disability were assessed by the Chronic Pain Grade Scale
      at the time of MRI. Intervertebral disc height and cross-sectional area and fat
      content of multifidus and erector spinae were assessed from MRI. RESULTS: Lower
      physical activity levels were associated with a more narrow average
      intervertebral disc height (beta -0.63 mm, 95% confidence interval (CI) -1.17 mm
      to -0.08 mm, P = 0.026) after adjusting for age, gender and body mass index
      (BMI). There were no significant associations between physical activity levels
      and the cross-sectional area of multifidus or erector spinae. Lower levels of
      physical activity were associated with an increased risk of high fat content in
      multifidus (odds ratio (OR) 2.7, 95% CI 1.1 to 6.7, P = 0.04) and high-intensity
      pain/disability (OR = 5.0, 95% CI 1.5 to 16.4, P = 0.008) after adjustment for
      age, gender and BMI. CONCLUSIONS: Physical inactivity is associated with narrower
      intervertebral discs, high fat content of the multifidus and high-intensity low
      back pain and disability in a dose-dependent manner among community-based adults.
      Longitudinal studies will help to determine the cause and effect nature of these
      associations.

PMID- 25947905
TI  - Prospective clinical trial of patients who underwent ankle arthroscopy with
      articular diseases to match clinical and radiological scores with intra-articular
      cytokines.
AB  - OBJECTIVE: There is still a lack of reliable data on cytokine concentrations in
      the ankle and their value for prognosis. METHODS: In a prospective clinical
      trial, lavage fluids were collected from 49 patients with an arthroscopy of the
      ankle. The fluids were investigated by ELISA for cytokine levels. Clinical scores
      (FFI, AOFAS) were evaluated both pre-operatively and then again 12 months after
      surgery (n = 43, 88%). Radiological changes were noted with the Kellgren-Lawrence
      Score (KLS) and the Ankle Osteoarthritis Scoring System (AOSS). Based on the
      difference between the pre- and postoperative clinical scores, two groups were
      defined according to whether they had benefited from the surgical therapy (Delta
      score >= 10) or not (Delta score < 10). RESULTS: The average clinical scores had
      improved to a statistically significant extent in the one-year follow-up (p <
      0.01). BMP-2 (p = 0.02), IGF-1 (p = 0.04), BMP-7 (p = 0.01) and aggrecan (p =
      0.04) showed significant correlations with pre-operative clinical and
      radiological scores (p = 0.02, p = 0.01, p = 0.01, p = 0.01). Furthermore, BMP-2
      (p = 0.01), IGF-1/TPC (p = 0.03) and aggrecan (p = 0.01) correlated with scores
      after one year (p = 0.02, p = 0.01). High aggrecan concentrations were associated
      with a low clinical and a high radiological score at both time points, both
      indicating progress of cartilage degeneration in contrast to BMP-2 or IGF-1.
      Furthermore, MMP-13 concentrations were significantly higher in the non-benefit
      group (p = 0.02). CONCLUSION: BMP-2, IGF-1, aggrecan and MMP-13 seem to be
      involved in the degenerative process of cartilage in the ankle joint.
      Additionally, high synovial MMP-13 concentrations indicate a worse clinical
      outcome.

PMID- 25947907
TI  - Methods for preclinical assessment of antipruritic agents and itch mechanisms
      independent of mast-cell histamine.
AB  - Itch is a sensation that provokes a desire to scratch. Mast-cell histamine was
      thought to be a key itch mediator. However, histamine and mast-cell degranulation
      were reported not to elicit scratching in animals. It was difficult to
      investigate the pathophysiology of itching and to evaluate the antipruritic
      efficacy of chemical agents in the early 1990 s. We showed that hind-paw
      scratching and biting were elicited by stimulation with pruritogenic agents in
      mice. Those results demonstrated for the first time that cutaneous itching could
      be evaluated behaviorally in animals. We established various animal models of
      pathological itch of the skin (dry skin, mosquito allergy, surfactant-induced
      pruritus, and herpes zoster) and mucus membranes (pollen allergy). Mast-cell
      histamine did not play a key role in itching in any animal model examined except
      for the pollen allergy model. Histamine is not an exclusive itch mediator of mast
      cells; tryptase and leukotriene B4 released from mast cells also act as itch
      mediators. Epidermal keratinocytes release several itch mediators, such as
      leukotriene B4, sphingosylphosphorylcholine, thromboxane A2, nociceptin, nitric
      oxide, and histamine, which may play important roles in pathological itching.
      Appropriate animal models of pathological itching are needed for pharmacological
      evaluation of the antipruritic efficacy of chemical agents. 

PMID- 25947909
TI  - Foreword.

PMID- 25947908
TI  - Therapeutic drug monitoring of imatinib, nilotinib, and dasatinib for patients
      with chronic myeloid leukemia.
AB  - Imatinib, nilotinib, and dasatinib are tyrosine kinase inhibitors (TKIs) that
      have become first-line treatments for Philadelphia chromosome-positive chronic
      myeloid leukemia (CML). According to European LeukemiaNet recommendations, the
      clinical response of CML patients receiving TKI therapy should be evaluated after
      3, 6, and 12 months. For patients not achieving a satisfactory response within 3
      months, the mean plasma concentration for the three months of TKI administration
      must be considered. In TKI therapy for CML patients, therapeutic drug monitoring
      is a new strategy for dosage optimization to obtain a faster and more effective
      clinical response. The imatinib plasma trough concentration (C0) should be set
      above 1000 ng/mL to obtain a response and below 3000 ng/mL to avoid serious
      adverse events such as neutropenia. For patients with a UGT1A1*6/*6, *6/*28, or
      *28/*28 genotype initially administered 300-400 mg/d, a target nilotinib C0 of
      500 ng/mL is recommended to prevent elevation of bilirubin levels, whereas for
      patients with the UGT1A1*1 allele initially administered 600 mg/d, a target
      nilotinib C0 of 800 ng/mL is recommended. For dasatinib, it is recommended that a
      higher Cmax or C2 (above 50 ng/mL) to obtain a clinical response and a lower C0
      (less than 2.5 ng/mL) to avoid pleural effusion be maintained by once daily
      administration of dasatinib. Although at present clinicians consider the next
      pharmacotherapy from clinical responses (efficacy/toxicity) obtained by a fixed
      dosage of TKI, the TKI dosage should be adjusted based on target plasma
      concentrations to maximize the efficacy and to minimize the incidence of adverse
      events.

PMID- 25947910
TI  - Imaging analysis of insulin secretion with two-photon microscopy.
AB  - High-resolution deep tissue imaging is possible with two-photon excitation
      microscopy. With the combined application of two-photon imaging and perfusion
      with a polar fluorescent tracer, we have established a method to detect exocytic
      events inside secretory tissues. This method displays the spatiotemporal
      distribution of exocytic sites, dynamics of fusion pores, and modes of
      exocytosis. In glucose-stimulated pancreatic islets, exocytic events were
      observed to be synchronized with an increase in cytosolic Ca(2+) concentrations.
      Full fusion of a single secretory granule is the typical mode of exocytosis and
      compound exocytosis is inhibited. Because two-photon excitation enables
      simultaneous multicolor imaging due to the broadened excitation spectra, the
      distributions and conformational changes in fluorescent-labeled molecules can be
      simultaneously visualized with exocytic events. Therefore, we can analyze the
      dynamics of the molecules involved in membrane fusion and their association with
      exocytosis in living tissues. 

PMID- 25947911
TI  - GTP- and GDP-Dependent Rab27a Effectors in Pancreatic Beta-Cells.
AB  - Small guanosine triphosphatases (GTPases) participate in a wide variety of
      cellular functions including proliferation, differentiation, adhesion, and
      intracellular transport. Conventionally, only the guanosine 5'-triphosphate (GTP)
      bound small GTPase interacts with effector proteins, and the resulting downstream
      signals control specific cellular functions. Therefore, the GTP-bound form is
      regarded as active, and the focus has been on searching for proteins that bind
      the GTP form to look for their effectors. The Rab family small GTPase Rab27a is
      highly expressed in some secretory cells and is involved in the control of
      membrane traffic. The present study reviews recent progress in our understanding
      of the roles of Rab27a and its effectors in pancreatic beta-cells. In the basal
      state, GTP-bound Rab27a controls insulin secretion at pre-exocytic stages via its
      GTP-dependent effectors. We previously identified novel guanosine 5'-diphosphate
      (GDP)-bound Rab27-interacting proteins. Interestingly, GDP-bound Rab27a controls
      endocytosis of the secretory membrane via its interaction with these proteins. We
      also demonstrated that the insulin secretagogue glucose converts Rab27a from its
      GTP- to GDP-bound forms. Thus, GTP- and GDP-bound Rab27a regulate pre-exocytic
      and endocytic stages in membrane traffic, respectively. Since the physiological
      importance of GDP-bound GTPases has been largely overlooked, we consider that the
      investigation of GDP-dependent effectors for other GTPases is necessary for
      further understanding of cellular function. 

PMID- 25947912
TI  - Diacylglycerol Signaling Pathway in Pancreatic beta-Cells: An Essential Role of
      Diacylglycerol Kinase in the Regulation of Insulin Secretion.
AB  - Diacylglycerol (DAG) is a lipid signal messenger and plays a physiological role
      in beta-cells. Since defective glucose homeostasis increases de novo DAG
      synthesis, DAG may also contribute to beta-cell dysfunction in type 2 diabetes.
      Although the primary function of DAG is to activate protein kinase C (PKC), the
      role of PKC in insulin secretion is controversial: PKC has been reported to act
      as both a positive and negative regulator of insulin secretion. In addition to
      the PKC pathway, DAG has also been shown to mediate other pathways such as the
      Munc-13-dependent pathway in beta-cells. The intracellular levels of DAG are
      strictly regulated by diacylglycerol kinase (DGK); however, the role of DGK in
      beta-cells and their involvement in beta-cell failure in type 2 diabetes remain
      to be fully elucidated. We have recently reported the roles of type I DGK,
      DGKalpha and gamma, in insulin secretion from beta-cells. DGKalpha and gamma were
      activated by glucose or high K(+) stimulation in beta-cells, and the inhibition
      of the DGKs by a type I DGK inhibitor or by knockdown with small interfering RNA
      (siRNA) decreased insulin secretion. Thus, DGKalpha and gamma are suggested to be
      activated in response to elevated [Ca(2+)]i in beta-cells and to act as positive
      regulators of insulin secretion. In this article, we review the current
      understanding of the roles of DAG and DGK in beta-cell function and their
      involvement in the development of beta-cell dysfunction in type 2 diabetes. 

PMID- 25947913
TI  - Glucose-Sensing Receptor T1R3: A New Signaling Receptor Activated by Glucose in
      Pancreatic beta-Cells.
AB  - Subunits of the sweet taste receptors T1R2 and T1R3 are expressed in pancreatic
      beta-cells. Compared with T1R3, mRNA expression of T1R2 is considerably lower. At
      the protein level, expression of T1R2 is undetectable in beta-cells. Accordingly,
      a major component of the sweet taste-sensing receptor in beta-cells may be a
      homodimer of T1R3 rather than a heterodimer of T1R2/T1R3. Inhibition of this
      receptor by gurmarin or deletion of the T1R3 gene attenuates glucose-induced
      insulin secretion from beta-cells. Hence the T1R3 homodimer functions as a
      glucose-sensing receptor (GSR) in pancreatic beta-cells. When GSR is activated by
      the T1R3 agonist sucralose, elevation of intracellular ATP concentration ([ATP]i)
      is observed. Sucralose increases [ATP]i even in the absence of ambient glucose,
      indicating that sucralose increases [ATP]i not simply by activating glucokinase,
      a rate-limiting enzyme in the glycolytic pathway. In addition, sucralose augments
      elevation of [ATP]i induced by methylsuccinate, suggesting that sucralose
      activates mitochondrial metabolism. Nonmetabolizable 3-O-methylglucose also
      increases [ATP]i and knockdown of T1R3 attenuates elevation of [ATP]i induced by
      high concentration of glucose. Collectively, these results indicate that the T1R3
      homodimer functions as a GSR; this receptor is involved in glucose-induced
      insulin secretion by activating glucose metabolism probably in mitochondria. 

PMID- 25947914
TI  - Analysis of the Interaction between Clopidogrel, Aspirin, and Proton Pump
      Inhibitors Using the FDA Adverse Event Reporting System Database.
AB  - Clopidogrel is an antiplatelet agent widely used in combination with aspirin to
      limit the occurrence of cardiovascular (embolic/thrombotic) events. Consensus
      guidelines recommend proton pump inhibitors (PPIs) as a gastrointestinal (GI)
      prophylactic measure for all patients receiving dual antiplatelet therapy with
      clopidogrel and aspirin. The objective of this study was to analyze the effect of
      the simultaneous use of clopidogrel, aspirin, and PPIs on hemorrhagic and
      embolic/thrombotic events using the U.S. Food and Drug Administration (FDA)
      Adverse Event Reporting System (FAERS) database. Reports of hemorrhagic and
      embolic/thrombotic events between 2004 and 2013 were analyzed with a reporting
      odds ratio (ROR) algorithm and logistic regression methods. The Medical
      Dictionary for Regulatory Activities Preferred Terms was used to identify such
      events. Regarding hemorrhagic events, the adjusted RORs of the concomitant use of
      aspirin and clopidogrel and those of PPIs prescribed with aspirin and clopidogrel
      were 4.40 (95% confidence interval [CI], 4.02-4.81) and 3.40 (95% CI, 2.84-4.06),
      respectively. For embolic/thrombotic events, the adjusted RORs of the concomitant
      use of aspirin and clopidogrel and those of PPIs prescribed with aspirin and
      clopidogrel were 2.37 (95% CI, 2.16-2.59) and 2.38 (95% CI, 2.00-2.84),
      respectively. Among patients included in the FAERS database, the concurrent use
      of aspirin and clopidogrel with PPIs reduced the adjusted ROR of GI hemorrhagic
      events. PPIs had little influence on the adjusted ROR of embolic/thrombotic
      events. These results support the use of PPIs as a preventive measure against GI
      hemorrhagic events for patients receiving clopidogrel and aspirin. 

PMID- 25947915
TI  - The Glucagon-Like Peptide-1 Analogue Liraglutide Inhibits Oxidative Stress and
      Inflammatory Response in the Liver of Rats with Diet-Induced Non-alcoholic Fatty
      Liver Disease.
AB  - Liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, has been demonstrated to
      reduce hepatic steatosis. However, the mechanism of the lipid-lowering effect of
      liraglutide in the liver remains unclear. The aim of the present study was to
      investigate the beneficial effect of liraglutide on diet-induced non-alcoholic
      fatty liver disease (NAFLD) and the underlying mechanism in rats. NAFLD was
      induced in Sprague-Dawley rats by feeding a high fat and high cholesterol (HFHC)
      diet. Liraglutide (0.6 mg/kg body weight/d) was injected intraperitoneally to the
      rats subjected to HFHC diet four weeks before sacrificing the animals. Body and
      liver weight, fasting blood glucose (FBG), fasting insulin, serum
      aminotransferase (ALT) and lipid accumulation in the liver were determined.
      Markers of oxidative stress, such as malondialdehyde (MDA), free fatty acid
      (FFAs), superoxide dismutase (SOD), and pro-inflammatory cytokine tumor necrosis
      factor-alpha (TNF-alpha) were detected by colorimetric detection or enzyme-linked
      immunosorbent assay (ELISA). Serum and hepatic adiponectin were measured by
      ELISA. The expression of c-Jun N-terminal kinase-1 (JNK-1) and phosphorylated JNK
      1 were examined by Western blotting. Liraglutide improved insulin resistance,
      decreased hepatic steatosis and reversed liver dysfunction. The hepatic levels of
      MDA, FFAs, and TNF-alpha were significantly decreased versus controls. Meanwhile,
      administration of liraglutide significantly increased SOD and adiponectin levels
      in the liver and inhibited the expression of JNK-1 and phosphorylated JNK-1
      versus control rats. Liraglutide exerted anti-oxidative and anti-inflammatory
      effects in the liver and consequently reversed hepatic steatosis and insulin
      resistance. Such effects might be mediated by the elevation of adiponectin levels
      and the inactivation of JNK-1. 

PMID- 25947916
TI  - Luteolin attenuates doxorubicin-induced cytotoxicity to MCF-7 human breast cancer
      cells.
AB  - Luteolin, a flavone found in some vegetables, has been reported to exhibit
      antioxidant, antiinflammatory, and anticancer activities. In the present study,
      we found that luteolin has biphasic effects on the viability of the human breast
      cancer cell line MCF-7. That is, cell viability increased at relatively low
      luteolin concentrations and decreased at relatively high concentrations. Focusing
      on the proliferative effect at low concentrations, we showed that luteolin has a
      cytoprotective effect on MCF-7 cells when administered with doxorubicin.
      Moreover, luteolin attenuated doxorubicin-induced cytotoxicity even in the
      presence of the estrogen receptor (ER) antagonist ICI 182,780 and the ER-negative
      MDA-MB-453 human breast cancer cell line. Reactive oxygen species (ROS) were
      generated after doxorubicin treatment of MCF-7 cells. In contrast, luteolin
      attenuated doxorubicin-induced ROS generation. Levels of the antiapoptotic
      protein Bcl-2 in luteolin-treated MCF-7 cells were significantly higher than
      those in doxorubicin-treated MCF-7 cells. Our results suggest that a low
      concentration of luteolin attenuates doxorubicin-induced cytotoxicity to MCF-7
      cells through a combination of antioxidant activity and an increase in levels of
      Bcl-2 protein. 

PMID- 25947917
TI  - Complestatin exerts antibacterial activity by the inhibition of fatty acid
      synthesis.
AB  - Bacterial enoyl-acyl carrier protein (ACP) reductase has been confirmed as a
      novel target for antibacterial drug development. In the screening of inhibitors
      of Staphylococcus aureus enoyl-ACP reductase (FabI), complestatin was isolated as
      a potent inhibitor of S. aureus FabI together with neuroprotectin A and
      chloropeptin I from Streptomyces chartreusis AN1542. Complestatin and related
      compounds inhibited S. aureus FabI with IC50 of 0.3-0.6 uM. They also prevented
      the growth of S. aureus as well as methicillin-resistance S. aureus (MRSA) and
      quinolone-resistant S. aureus (QRSA), with minimum inhibitory concentrations
      (MICs) of 2-4 ug/mL. Consistent with its FabI-inhibition, complestatin
      selectively inhibited the intracellular fatty acid synthesis in S. aureus,
      whereas it did not affect the macromolecular biosynthesis of other cellular
      components, such as DNA, RNA, proteins, and the cell wall. Additionally,
      supplementation with exogenous fatty acids reversed the antibacterial effect of
      complestatin, demonstrating that it targets fatty acid synthesis. In this study,
      we reported that complestatin and related compounds showed potent antibacterial
      activity via inhibiting fatty acid synthesis.

PMID- 25947918
TI  - Characterization of the Role of MANF in Regulating the Secretion of CRELD2.
AB  - We recently demonstrated that the secretion of two novel endoplasmic reticulum
      (ER) stress-inducible proteins, cysteine-rich with epidermal growth factor (EGF)
      like domains 2 (CRELD2) and mesencephalic astrocyte-derived neurotrophic factor
      (MANF), are oppositely regulated by the overexpression of 78 kDa glucose
      regulated protein (GRP78). In the present study, we found that the co
      transfection of CRELD2 and MANF remarkably enhanced the secretion of CRELD2
      without affecting the expression level of GRP78. To identify the structural
      features of CRELD2 and MANF involved in this process, we generated several CRELD2
      and MANF expression constructs. The deletion of the four C-terminal amino acids,
      either REDL in CRELD2 or RTDL in MANF, abolished the increased secretion of
      CRELD2 induced by the co-expression of MANF. The deleted mutation of MANF
      partially abolished the increased secretion of wild type CRELD2 (wtCRELD2) as a
      positive action of wild type MANF (wtMANF), even when we added the amino acid
      sequence RTDL at the C-terminus of each mutated MANF construct. Enhanced green
      fluorescent protein (EGFP), which was tagged with the signal peptide sequence at
      the N-terminus and four C-terminal amino acids (KEDL, REDL or RTDL), were
      retained intracellularly, but they did not enhance the secretion of wtCRELD2.
      Taken together, our data demonstrate that MANF is a factor in regulating the
      secretion of CRELD2 through four C-terminal amino acids, RTDL and REDL, and the
      fluctuation of intracellular MANF seems to potentiate the secretion of CRELD2. 

PMID- 25947919
TI  - Clostridium perfringens TpeL Induces Formation of Stress Fibers via Activation of
      RhoA-ROCK Signaling Pathway.
AB  - Clostridium perfringens TpeL belongs to a family of large clostridial
      glucosylating cytotoxins. TpeL modifies Rac1 and Ras subfamily proteins. Herein
      we report TpeL-induced formation of stress fibers via RhoA-Rho kinase (ROCK)
      signaling. A recombinant protein (TpeL1-525) derived from the TpeL N-terminal
      catalytic domain in the presence of streptolysin O (SLO) induced the formation of
      actin stress fibers in Madin-Darby canine kidney (MDCK) cells in a dose-dependent
      manner. The RhoA/ROCK pathway is known to control the formation of stress fibers.
      We examined the role of the RhoA/ROCK pathway in TpeL-induced formation of stress
      fibers. TpeL1-525-induced formation of stress fibers was inhibited by the ROCK
      inhibitor, Y27632 and Rho protein inhibitor, C3 transferase. TpeL1-525 activated
      RhoA and ROCK in a dose-dependent manner. C3 transferase blocked TpeL1-525
      induced activation of RhoA and ROCK whereas Y27632 inhibited TpeL-induced
      activation of ROCK. These results demonstrate for the first time that TpeL
      induces the formation of stress fibers by activating the RhoA/ROCK signaling
      pathway. 

PMID- 25947920
TI  - In a methotrexate-induced model of intestinal mucositis, olmesartan reduced
      inflammation and induced enteropathy characterized by severe diarrhea, weight
      loss, and reduced sucrose activity.
AB  - The aim of this study was to evaluate the effect of olmesartan (OLME), an
      angiotensin II receptor antagonist, on an intestinal mucositis model. Briefly,
      daily intraperitoneal (i.p.) injections of methotrexate (MTX) 7 mg/kg were
      administered to rats on 3 consecutive days. A subset of these rats was also
      pretreated with oral administration of OLME (0.5, 1.0, or 5.0 mg/kg) or vehicle
      as a control 30 min prior to MTX injection. Body weight, feces scoring, and death
      were recorded daily. On day 4, the rats were killed, and intestinal tissues were
      assayed for levels of interleukin (IL)-1beta and tumor necrosis factor (TNF)
      alpha, myeloperoxidase and sucrose activity, and histopathological findings. A
      significant reduction in body weight was observed in the MTX+1.0 mg/kg OLME group
      (p<0.01). The feces scores for the MTX+0.5 mg/kg OLME and MTX+5.0 mg/kg OLME
      groups were also significantly higher (p<0.001). Sucrose activity was reduced in
      all groups treated with OLME (p<0.05). Treatment with MTX+OLM at all doses
      resulted in reduced inflammatory infiltration, ulcerations, vasodilation, and
      hemorrhagic areas (p<0.05), as well as reduced concentrations of myeloperoxidase
      (p<0.001). The IL-1beta and TNF-alpha levels were decreased in the MTX+OLME 5.0
      mg/kg (p<0.01 and p<0.05, respectively) compared with the MTX-alone group.
      Overall, antiinflammatory activity was observed in rats with MTX-induced
      intestinal mucositis that were administered OLME. However, further studies are
      needed to elucidate the adverse effects of OLME. 

PMID- 25947921
TI  - Losartan and Sodium Nitroprusside Effectively Protect against Renal Impairments
      after Ischemia and Reperfusion in Rats.
AB  - Ischemia and subsequent reperfusion are known to impair renal function. We
      examined several agents that might prevent renal impairment or enhance the
      recovery of renal function after ischemia/reperfusion injury in rats. Different
      degrees of preventive effects were observed in rats treated with captopril, BQ
      123 (endothelin type A receptor antagonist), sodium nitroprusside (SNP, a nitric
      oxide donor), and losartan (angiotensin II type 1 receptor antagonist). Only
      minimal changes in renal morphology were observed after treatment with losartan,
      SNP, captopril, and BQ-123 compared with control animals. On the other hand,
      lesions were prominent in the N(G)-nitro-L-arginine-methyl ester (L-NAME)- and L
      arginine-treated rats. The Na(+)-K(+) ATPase activity of ischemic kidneys was,
      however, preserved in all treatment groups, except in those treated with L
      arginine and L-NAME, which showed a marked reduction in Na(+)-K(+) ATPase
      activity. Our post-treatment data suggest that losartan and SNP have the greatest
      potential for therapeutic use to mitigate post-ischemic renal damage and
      functional impairment. 

PMID- 25947922
TI  - Design, Synthesis, and Antitumor Activity of Novel 5-Pyridyl-1,3,4-oxadiazole
      Derivatives against the Breast Cancer Cell Line MCF-7.
AB  - Various 1,3,4-oxadiazole-2-thiol derivatives have considerable potential in the
      field of antitumor activity. On the basis of the structure of the highly active
      reported oxadiazole analogues, 36 novel compounds were designed. Their molecular
      transport properties were predicted using a computer-aided program, and they were
      then synthesized and tested for anticancer activity against the breast cancer
      cell line MCF-7. Most of the tested compounds showed excellent to potent
      cytotoxic activity. Docking studies were carried out to examine the possibilities
      of the target compounds to become lead compounds in the future after more
      biological investigations. Compounds 18 and 22 were more active than the
      reference drug with IC50 values of 0.010 uM and 0.012 uM, respectively, and
      binding energy scores of -10.32 and -10.25, respectively.

PMID- 25947923
TI  - Gene ablation of carnitine/organic cation transporter 1 reduces gastrointestinal
      absorption of 5-aminosalicylate in mice.
AB  - 5-Aminosalicylic acid (5-ASA) is an orally administered therapeutic agent for
      inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease. We
      hypothesized that the absorption of 5-ASA is mediated by the polyspecific
      carnitine/organic cation transporter (OCTN1/SLC22A4), based on the similarity of
      chemical structure between 5-ASA and other OCTN1 substrates. Therefore, we
      examined the involvement of this transporter in the disposition of 5-ASA in vivo
      by using octn1 gene knockout (octn1(-/-)) mice. After oral administration of 5
      ASA, the plasma concentrations of 5-ASA and its primary metabolite, N-acetyl-5
      aminosalicylate (Ac-5-ASA), in octn1(-/-) mice were much lower than those in wild
      type mice. The time required to reach maximum plasma concentration was also
      delayed in octn1(-/-) mice. On the other hand, the plasma concentration profiles
      of both 5-ASA and Ac-5-ASA after intravenous administration of 5-ASA (bolus or
      infusion) were similar in the two strains. Uptake of 5-ASA from the apical to the
      basal side of isolated small-intestinal tissues of octn1(-/-) mice, determined in
      an Ussing-type chamber, was lower than that in wild-type mice. Further, uptake of
      5-ASA in HEK293 cells stably transfected with the OCTN1 gene, assessed as the sum
      of cell-associated 5-ASA and Ac-5-ASA, was higher than that in HEK293 cells
      transfected with the vector alone. Overall, these results indicate that OCTN1 is
      involved, at least in part, in the gastrointestinal absorption of 5-ASA. 

PMID- 25947924
TI  - The Susceptibilities of Human Ether-a-Go-Go-Related Gene Channel with the G487R
      Mutation to Arrhythmogenic Factors.
AB  - The human ether-a-go-go-related gene (hERG) channel mediates the rapid delayed
      rectifier potassium current (IKr) responsible for shaping the repolarization
      phase of cardiac action potentials. hERG mutation may cause hERG channel
      malfunction, leading to long QT syndrome and other arrhythmic disorders.
      Elucidation of the genotype-phenotype relationships of individual hERG mutations
      is key to the development of treatment for such arrhythmic disorders. We
      previously identified hERG(G487R), a missense mutant with a glycine-to-arginine
      substitution at position 487. In the absence of arrhythmogenic factors,
      hERG(G487R) subunit-containing channels show normal surface expression and gating
      kinetics. However, it remains unknown whether the mutation exacerbates hERG
      channel malfunction induced by arrhythmogenic factors. Here we used a voltage
      clamp technique to compare the effects of the major arrythmogenic factors on wild
      type hERG [hERG(WT)] and hERG(G487R) channel currents (IhERG) in HEK-293T cells.
      The extent of IhERG blockade by the antiarrhythmic drug dofetilide or E4031 was
      not different between these channels. On the other hand, the extracellular K(+)
      concentration ([K(+)]ex)-dependent changes in the rates of recovery from
      inactivation and deactivation of IhERG were rather less obvious for hERG(G487R)
      channel than for hERG(WT) channel. These findings suggest that the inheritance of
      hERG(G487R) does not increase the risk of arrhythmic disorders induced by
      antiarrhythmic drugs or hypokalemia. 

PMID- 25947925
TI  - Dietary cholesterol atherogenic changes in juvenile rabbits.
AB  - Atherosclerotic lesion formation starts during fetal development and progresses
      with age after adolescence. However, atherogenesis during the juvenile period has
      not been studied thoroughly. In this study, we examined the atherogenic
      susceptibility of juvenile rabbits to cholesterol feeding. Male New Zealand White
      rabbits aged 8 (younger group) and 12 (older group) weeks were fed a 0.5%
      cholesterol-containing diet for 8 weeks, and then their aortic atherosclerotic
      lesion areas were evaluated. Plasma concentrations of total cholesterol,
      triglycerides, and phospholipids did not differ between the two groups; however,
      plasma concentrations of high-density lipoprotein cholesterol were 23% lower in
      the younger than in the older group. Atherosclerotic lesion areas were
      significantly larger in the younger group (32+/-21%). However, only moderate
      changes were observed in these areas in the older group (3.3+/-0.3%).
      Histological examination showed marked intimal thickening and macrophage
      accumulation in the aortic lesions of rabbits in the younger group. To the best
      of our knowledge, this is the first study to show that dietary cholesterol
      induced atherogenic changes markedly occur during a short period in juvenile
      rabbits. 

PMID- 25947926
TI  - Bioconversion of (-)-epicatechin, (+)-epicatechin, (-)-catechin, and (+)-catechin
      by (-)-epigallocatechin-metabolizing bacteria.
AB  - Bioconversion of (-)-epicatechin (-EC), (+)-epicatechin (+EC), (-)-catechin (-C),
      and (+)-catechin (+C) by (-)-epigallocatechin (-EGC)-metabolizing bacteria,
      Adlercreutzia equolifaciens MT4s-5, Eggerthella lenta JCM 9979, and
      Flavonifractor plautii MT42, was investigated. A. equolifaciens MT4s-5 could
      catalyze C ring cleavage to form (2S)-1-(3,4-dihydroxyphenyl)-3-(2,4,6
      trihydroxyphenyl)propan-2-ol (1S) from -EC and -C, and (2R)-1-(3,4
      dihydroxyphenyl)-3-(2,4,6-trihydroxyphenyl)propan-2-ol (1R) from +C. The C ring
      cleavage by A. equolifaciens MT4s-5 was accelerated in the presence of hydrogen.
      E. lenta JCM 9979 also catalyzed C ring cleavage of -EC and +C to produce 1S and
      1R, respectively. In the presence of hydrogen or formate, strain JCM 9979 showed
      not only stimulation of C ring cleavage but also subsequent 4'-dehydroxylation of
      1S and 1R to produce (2S)-1-(3-hydroxyphenyl)-3-(2,4,6-trihydroxyphenyl)propan-2
      ol (2S) and (2R)-1-(3-hydroxyphenyl)-3-(2,4,6-trihydroxyphenyl)propan-2-ol (2R),
      respectively. On the other hand, A. equolifaciens MT4s-5 did not show any 4'
      dehydroxylation ability even in the presence of hydrogen. F. plautii MT42 could
      convert 1S, 1R, 2S, and 2R into their corresponding 4-hydroxy-5
      hydroxyphenylvaleric acids and 5-hydroxyphenyl-gamma-valerolactones
      simultaneously. Similar bioconversion was observed by F. plautii ATCC 29863 and
      F. plautii ATCC 49531. 

PMID- 25947927
TI  - A pyrosequencing-based analysis of microbial diversity governed by ecological
      conditions in the Winogradsky column.
AB  - The Winogradsky column is used as a microcosm to mimic both the microbial
      diversity and the ecological relationships between the organisms in lake
      sediments. In this study, a pyrosequencing approach was used to obtain a more
      complete list of the microbial organisms present in such columns and their ratios
      in different layers of this microcosm. Overall, 27 different phyla in these
      columns were detected in these columns, most (20 phyla) belonged to bacteria.
      Based on this study, Proteobacteria (mostly Sphingomonadales), Cyanobacteria
      (mostly Oscillatoriales) and Bacteroidetes (mostly Flavobacteriales) were the
      dominant microorganisms in the water, middle, and bottom layers of this column,
      respectively. Although the majority of organism in the water layer were
      photoautotrophic organisms, the ratio of the phototrophic organisms decreased in
      the lower layers, replaced by chemoheterotrophic bacteria. Furthermore, the
      proportion of aerobic chemoheterotrophic bacteria was greater in the higher
      layers of the column in comparison to the bottom. The green and purple sulfur
      phototrophic bacteria inhabited the bottom and middle of these columns, with none
      of them found in the water layer. Although the sulfur oxidizing bacteria were the
      dominant chemolithotrophic bacteria in the water layer, their ratio decreases in
      lower layers, being replaced with nitrogen oxidizing bacteria in the middle and
      bottom layers. Overall, the microbial population of these layers changes from a
      phototrophic and aerobic chemoheterotrophic organisms in the water layer to a
      mostly anaerobic chemoheterotrophic population of bacteria in the bottom layers.

PMID- 25947928
TI  - Use of the GuideLiner catheter for aspiration thrombectomy in a patient with ST
      elevation myocardial infarction with a large intracoronary thrombus.
AB  - We report a 67-year-old man with ST-elevation myocardial infarction with a large
      intracoronary thrombus who was successfully treated with percutaneous
      thrombectomy using the GuideLiner catheter. This catheter is designed for the
      "Mother and Child" technique with a rapid exchange system and it has a larger
      internal diameter than conventional aspiration devices. When aspiration
      thrombectomy using a conventional aspiration catheter is not feasible or fails,
      use of the GuideLiner catheter for aspiration of thrombus is a reasonable
      alternative for primary percutaneous coronary intervention in patients with acute
      myocardial infarction. 

PMID- 25947929
TI  - Supporting "second victims" is a system-wide responsibility.

PMID- 25947930
TI  - A Phase II, Randomized, Double-Blind, Placebo Controlled, Dose-Response Trial of
      the Melatonin Effect on the Pain Threshold of Healthy Subjects.
AB  - BACKGROUND: Previous studies have suggested that melatonin may produce
      antinociception through peripheral and central mechanisms. Based on the
      preliminary encouraging results of studies of the effects of melatonin on pain
      modulation, the important question has been raised of whether there is a dose
      relationship in humans of melatonin on pain modulation. OBJECTIVE: The objective
      was to evaluate the analgesic dose response of the effects of melatonin on
      pressure and heat pain threshold and tolerance and the sedative effects. METHODS:
      Sixty-one healthy subjects aged 19 to 47 y were randomized into one of four
      groups: placebo, 0.05 mg/kg sublingual melatonin, 0.15 mg/kg sublingual melatonin
      or 0.25 mg/kg sublingual melatonin. We determine the pressure pain threshold
      (PPT) and the pressure pain tolerance (PPTo). Quantitative sensory testing (QST)
      was used to measure the heat pain threshold (HPT) and the heat pain tolerance
      (HPTo). Sedation was assessed with a visual analogue scale and bispectral
      analysis. RESULTS: Serum plasma melatonin levels were directly proportional to
      the melatonin doses given to each subject. We observed a significant effect
      associated with dose group. Post hoc analysis indicated significant differences
      between the placebo vs. the intermediate (0.15 mg/kg) and the highest (0.25
      mg/kg) melatonin doses for all pain threshold and sedation level tests. A linear
      regression model indicated a significant association between the serum melatonin
      concentrations and changes in pain threshold and pain tolerance (R(2)  = 0.492
      for HPT, R(2)  = 0.538 for PPT, R(2)  = 0.558 for HPTo and R(2)  = 0.584 for
      PPTo). CONCLUSIONS: The present data indicate that sublingual melatonin exerts
      well-defined dose-dependent antinociceptive activity. There is a correlation
      between the plasma melatonin drug concentration and acute changes in the pain
      threshold. These results provide additional support for the investigation of
      melatonin as an analgesic agent. Brazilian Clinical Trials Registry (ReBec):
      (U1111-1123-5109). IRB: Research Ethics Committee at the Hospital de Clinicas de
      Porto Alegre.

PMID- 25947931
TI  - Effectiveness of home visiting in reducing partner violence for families
      experiencing abuse: a systematic review.
AB  - BACKGROUND: Intimate partner violence (IPV) against women is a major, global
      societal problem with enormous health consequences both for mother and child.
      Home visiting interventions in families at risk of abuse seem promising in
      decreasing IPV. In this systematic review, we aim to assess the effectiveness of
      home visiting in reducing IPV experienced by mothers. METHODS: We conducted a
      systematic review using the Pubmed, PsychINFO and Embase databases from inception
      until March 2014, with a specific search strategy for each database. RESULTS: Of
      the 1258 articles identified, 19 (six different home visiting studies) met our
      inclusion criteria and were examined in detail. Three different types of studies
      were identified: the primary focus of one study was on the abused mother and the
      secondary focus on the children (Australia); two studies (Hawaii, The
      Netherlands) with a primarily focus on reduction of child abuse and a secondary
      focus on IPV and finally three studies from the USA, which only aimed at reducing
      child abuse by providing support to the mother. The Australian study reported a
      significant lowering of the IPV score at 1-year follow-up (15.9 versus 21.8,
      adjusted difference -8.67, 95% confidence interval [CI]: -16.2 to -1.15). The
      Hawaii-study showed significantly lower rates of physical assault after 3 years
      follow-up (incidence rate ratio [IRR] 0.85; 95% CI: 0.71-1.00) and the Dutch
      study showed a significant decrease of mothers' physical assaults 2 years after
      birth (odds ratio 0.46; 95% CI 0.24-0.89). The other three studies showed no
      significant reduction of IPV. CONCLUSIONS: Home visiting interventions that
      support abused women explicit to stop IPV seem to be effective in reducing IPV.
      However, it is not known whether these results are effective in the long term.

PMID- 25947932
TI  - Second opinion in spine surgery: a Brazilian perspective.
AB  - The authors present their experience in a programme for second opinion evaluation
      of spine surgery candidates within a cohort of patients from a healthcare
      provider in Brazil. Ninety-four patients were evaluated, and the second opinion
      was divided in complete agreement, partial disagreement, and complete
      disagreement. Patients with complete disagreement were referred for a third
      medical opinion. A complete agreement was found in 22 cases, partial disagreement
      in 28 cases, and complete disagreement in 44 cases. The majority of the
      discrepancies between first and second opinion were found in lumbar degenerative
      disorders, with a reduction of 50% in the amount of surgical procedures and a 50%
      reduction in the rate of instrumentation within this subset of patients. Within 1
      year of the index evaluation, only two patients who followed the proposed
      treatment guidelines were reoperated, giving an estimate of the adequacy of this
      second opinion programme.

PMID- 25947933
TI  - Evaluation of psychosomatic distress and its influence in the outcomes of lumbar
      fusion procedures for degenerative disorders of the spine.
AB  - The authors aim to evaluate the ability of spine surgeons to subjectively
      identify patients with psychological distress in a subset of lumbar fusion
      candidates, and the influence of such factors on surgical outcomes. From a cohort
      of 85 patients who had received a surgical indication for lumbar fusion and were
      subjectively evaluated for psychological distress, 60 were included in the study
      and underwent objective evaluation using the Distress Risk Assessment Method
      (DRAM) evaluation for depressive/distress symptoms, VAS and Oswestry scores pre-
      and postoperatively. Fifty-six patients were available with a minimum 6-month
      follow-up: 20 presented with normal DRAM scores, and 36 with abnormal DRAM (28 at
      risk; 4 distressed somatic; 4 distressed depressive). Although the group improved
      significantly with surgery regarding VAS and Oswestry, it was not the case for
      the DRAM score. The abnormal DRAM group had inferior VAS, Oswestry and
      satisfaction rates in comparison with the normal DRAM group. A significant number
      of patients in the at-risk group reduced their DRAM scores and were classified as
      normal patients at the end of the study. This study emphasizes the need for
      objective psychological screening on chronic low back pain patients and that
      although patients with abnormal DRAM scores benefit from surgery, they report
      inferior outcomes and satisfaction in comparison with the normal DRAM group. 

PMID- 25947934
TI  - Effects of Graded Levels of Chromium Methionine on Performance, Carcass Traits,
      Meat Quality, Fatty Acid Profiles of Fat, Tissue Chromium Concentrations, and
      Antioxidant Status in Growing-Finishing Pigs.
AB  - A 97-day feeding trial was conducted to investigate the effects of dietary
      chromium methionine (CrMet) on performance, carcass traits, meat quality, fatty
      acid profiles of fat, tissue chromium concentrations, and antioxidant status in
      growing-finishing pigs. A total of 180 crossbred pigs with a mean initial body
      weight (BW) 30.18 +/- 0.28 kg were allotted to 5 treatments with 6 replicates per
      treatment and 6 pigs per pen in a randomized complete block design based on BW
      and sex. Treatments were added with 0 (control), 100, 200, 400, and 800 MUg/kg
      chromium as CrMet. Blood samples were obtained from the anterior vena cava on
      days 97. Carcass characteristics, pork quality, and tissue chromium concentration
      data were collected from one pig per pen. The results indicated that supplemental
      CrMet did not significantly affect growth performance, carcass traits, or meat
      amino acid profiles. Chromium at 100, 400, and 800 MUg/kg decreased drip loss but
      increased shear force (P < 0.05). Pigs fed 100 or 400 MUg/kg had a higher 24-h pH
      than the control (P < 0.05). While meat color, muscle moisture, crude protein, or
      crude fat were not affected by CrMet. Supplemental 800 MUg/kg chromium reduced
      C18:0 levels in belly fat (P < 0.05), and chromium supplementation increased cis
      9, trans 11-conjugated linoleic acid levels linearly (P < 0.05). Dietary CrMet
      supplementation increased serum, kidney, and muscle chromium contents (P < 0.05)
      but did not affect liver chromium contents. Besides, tissue chromium
      concentrations were increased linearly with increased chromium dosage (P < 0.05).
      Chromium at 400 MUg/kg increased serum glutathione peroxidase activities (P <
      0.05), and chromium at 800 MUg/kg decreased serum total antioxidant capacity
      levels (P < 0.05). Nevertheless, liver and kidney antioxidant status were not
      significantly affected by CrMet. These results indicated that dietary
      supplementation CrMet did not significantly influence growth and carcass traits,
      but improved meat quality at the expense of tenderness. Therefore, the long-term
      exposure to 800 MUg/kg chromium affected fatty acid compositions and reduced
      serum antioxidant capacity. 

PMID- 25947935
TI  - Variation in the Levels of Aluminum and Manganese in Scalp Hair Samples of the
      Patients Having Different Psychiatric Disorders with Related to Healthy Subjects.
AB  - There is very limited information available on the role of trace elements in
      psychiatric disorders (PSD). Immense pieces of evidence support the idea that
      exposure to trace and toxic metals, such as aluminum (Al) and manganese (Mn), may
      be factors or cofactors in the etiopathogenesis of a variety of psychiatric
      disorders. The aim of our study was to assess the Al and Mn in scalp hair samples
      of 102 patients having different types of psychiatric disorder PSD diseases
      together with 120 referent subjects of male patients in the age group of 45-60
      years. The understudy elements in scalp hair samples were assessed by the flame
      atomic absorption spectrophotometry after microwave-assisted acid digestion
      method .The validity of methodology was checked by the certified human hair
      reference material (NCS ZC81002). The recovery of studied elements was found in
      the range of 98.1-99.2 % of certified reference material. The results of this
      study showed that the mean values of Al and Mn were significantly higher in scalp
      hair samples of all types of PSD as compared to referents subjects. The resulted
      data indicated a significant increase in the contents of Mn and Al in scalp hair
      samples of psychiatric patients than that of its control counterpart, which may
      provide prognostic tool for the diagnosis of the mental disorders. However,
      further work is suggested to examine the exact correlation between trace elements
      level and the degree of disorder. 

PMID- 25947937
TI  - Single Case Method in Psychology: How to Improve as a Possible Methodology in
      Quantitative Research.
AB  - Awareness of including Single-Case Method (SCM), as a possible methodology in
      quantitative research in the field of psychology, has been argued as useful,
      e.g., by Hurtado-Parrado and Lopez-Lopez (IPBS: Integrative Psychological &
      Behavioral Science, 49:2, 2015). Their article introduces a historical and
      conceptual analysis of SCMs and proposes changing the, often prevailing, tendency
      of neglecting SCM as an alternative to Null Hypothesis Significance Testing
      (NHST). This article contributes by putting a new light on SCM as an equally
      important methodology in psychology. The intention of the present article is to
      elaborate this point of view further by discussing one of the most fundamental
      requirements as well as main characteristics of SCM regarding temporality. In
      this respect that; "...performance is assessed continuously over time and under
      different conditions..." Hurtado-Parrado and Lopez-Lopez (IPBS: Integrative
      Psychological & Behavioral Science, 49:2, 2015). Defining principles when it
      comes to particular units of analysis, both synchronic (spatial) and diachronic
      (temporal) elements should be incorporated. In this article misunderstandings of
      the SCM will be adduced, and further the temporality will be described in order
      to propose how the SCM could have a more severe usability in psychological
      research. It is further discussed how to implement SCM in psychological
      methodology. It is suggested that one solution might be to reconsider the notion
      of time in psychological research to cover more than a variable of control and in
      this respect also include the notion of time as an irreversible unity within
      life. 

PMID- 25947936
TI  - Curcumin Ameliorates Lead (Pb(2+))-Induced Hemato-Biochemical Alterations and
      Renal Oxidative Damage in a Rat Model.
AB  - This study aims to evaluate the protective role of curcumin (Curc) against
      hematological and biochemical changes, as well as renal pathologies induced by
      lead acetate [Pb (CH3COO)2.3H2O] treatment. Male albino rats were
      intraperitoneally treated with Pb(2+) (25 mg of lead acetate/kg b.w., once a day)
      alone or in combination with Curc (30 mg of Curc/kg b.w., twice a day) for 7
      days. Exposure of rats to Pb(2+) caused significant decreases in hemoglobin (Hb)
      content, hematocrit (Ht) value, and platelet (Plt) count, while Pb(2+)-related
      leukocytosis was accompanied by absolute neutrophilia, monocytosis, lymphopenia,
      and eosinopenia. A significant rise in lipid peroxidation (LPO) and a marked drop
      of total antioxidant capacity (TAC) were evident in the kidney, liver, and serum
      of Pb(2+) group compared to that of control. Furthermore, significantly high
      levels of total cholesterol (TC), triglycerides (TGs), and low-density
      lipoprotein cholesterol (LDL-C), and a sharp drop in serum high-density
      lipoprotein (HDL-C) level were also seen in blood after injection of Pb(2+).
      Additionally, hepatorenal function tests were enhanced. Meanwhile, Pb(2+)
      produced marked histo-cytological alterations in the renal cortex. Co
      administration of Curc to the Pb(2+)-treated animals restored most of the
      parameters mentioned above to near-normal levels/features. In conclusion, Curc
      appeared to be a promising agent for protection against Pb(2+)-induced toxicity. 

PMID- 25947938
TI  - Extracellular DNA and histones as thrombus stabiliser.

PMID- 25947939
TI  - Correlated structural-optical study of single nanocrystals in a gap-bar antenna:
      effects of plasmonics on excitonic recombination pathways.
AB  - We performed time-correlated single-photon counting experiments on individual
      silica coated CdSe/CdS core/thick-shell nanocrystal quantum dots (a.k.a., giant
      NQDs [g-NQDs]), placed on the plasmonic gap-bar antennas. Optical properties were
      directly correlated with the scanning electron microscopy (SEM) images of g-NQD
      plasmonic antenna coupled structures. The structures, in which the g-NQDs are
      located in the gap of the antenna, afford a coupling with up to 9.6 fold
      enhancement of radiative recombination rates. These coupled g-NQDs are also
      characterized by a strong enhancement of bi-exciton emission efficiency that
      increases with their radiative enhancement factor. By analysing these findings
      with a simple model, we show that the plasmonic field of the antenna does not
      alter the Auger recombination processes of the bi-exciton states. As a result,
      enhancements of the single and bi-exciton radiative recombination rates lead
      directly to bi-exciton emission enhancement. These findings suggest that a
      plasmonic field can be utilized effectively in achieving a strong bi-exciton
      emission that is needed for photon pair generation and plasmon-assisted lasing. 

PMID- 25947940
TI  - Functional role of a polymorphism in the Pannexin1 gene in collagen-induced
      platelet aggregation.
AB  - Pannexin1 (Panx1) forms ATP channels that play a critical role in the immune
      response by reinforcing purinergic signal amplification in the immune synapse.
      Platelets express Panx1 and given the importance of ATP release in platelets, we
      investigated Panx1 function in platelet aggregation and the potential impact of
      genetic polymorphisms on Panx1 channels. We show here that Panx1 forms ATP
      release channels in human platelets and that inhibiting Panx1 channel function
      with probenecid, mefloquine or specific (10)Panx1 peptides reduces collagen
      induced platelet aggregation but not the response induced by arachidonic acid or
      ADP. These results were confirmed using Panx1-/- platelets. Natural variations
      have been described in the human Panx1 gene, which are predicted to induce non
      conservative amino acid substitutions in its coding sequence. Healthy subjects
      homozygous for Panx1-400C, display enhanced platelet reactivity in response to
      collagen compared with those bearing the Panx1-400A allele. Conversely, the
      frequency of Panx1-400C homozygotes was increased among cardiovascular patients
      with hyper-reactive platelets compared with patients with hypo-reactive
      platelets. Exogenous expression of polymorphic Panx1 channels in a Panx-deficient
      cell line revealed increased basal and stimulated ATP release from cells
      transfected with Panx1-400C channels compared with Panx1-400A expressing
      transfectants. In conclusion, we demonstrate a specific role for Panx1 channels
      in the signalling pathway leading to collagen-induced platelet aggregation. Our
      study further identifies for the first time an association between a Panx1-400A>C
      genetic polymorphism and collagen-induced platelet reactivity. The Panx1-400C
      variant encodes for a gain-of-function channel that may adversely affect
      atherothrombosis by specifically enhancing collagen-induced ATP release and
      platelet aggregation. 

PMID- 25947941
TI  - A Transporter Motor Taken Apart: Flexibility in the Nucleotide Binding Domains of
      a Heterodimeric ABC Exporter.
AB  - ABC exporters are ubiquitous multidomain transport proteins that couple ATP
      hydrolysis at a pair of nucleotide binding domains to substrate transport across
      the lipid bilayer mediated by two transmembrane domains. Recently, the crystal
      structure of the heterodimeric ABC exporter TM287/288 was determined. One of its
      asymmetric ATP binding sites is called the degenerate site; it binds nucleotides
      tightly but is impaired in terms of ATP hydrolysis. Here we report the crystal
      structures of both isolated motor domains of TM287/288. Unexpectedly, structural
      elements constituting the degenerate ATP binding site are disordered in these
      crystals and become structured only in the context of the full-length
      transporter. In addition, hydrogen bonding patterns of key residues, including
      those of the catalytically important Walker B and the switch loop motifs, are
      fundamentally different in the solitary NBDs compared to those in the intact
      transport protein. The structures reveal crucial interdomain contacts that need
      to be established for the proper assembly of the functional transporter complex. 

PMID- 25947943
TI  - Microwave-assisted synthesis of novel non-peripherally substituted
      metallophthalocyanines and their sensing behaviour for a broad range of Lewis
      bases.
AB  - The synthesis of novel, symmetrical, tetrasubstituted metallophthalocyanines
      (cobalt, zinc, and manganese) bearing four 2-(4-methyl-1,3-thiazol-5-yl)ethoxy
      units is reported. The new compounds have been characterized using UV-Vis, IR,
      (1)H NMR, (13)C NMR, and mass spectroscopy data. Photophysical properties of
      zinc(ii) phthalocyanines were found, including electronic absorption and
      fluorescence quantum yields. The fluorescence of the complexes was investigated
      in DMF and it was found that benzoquinone (BQ) was an effective quencher. The
      response and recovery behaviours of the spin coated films to different analytes,
      which span a broad range of Lewis bases, have been investigated by means of
      conductivity measurements. It was observed that the operating temperature had a
      considerable effect on the gas sensing performance of the sensors investigated.
      The sensing behaviour of the films for a broad range of Lewis bases and the
      correlation between the sensor sensitivity and Lewis base enthalpies were
      investigated. Results show that the sensitivity of the films may be correlated
      exponentially with the binding enthalpy. 

PMID- 25947942
TI  - VPS33B regulates protein sorting into and maturation of alpha-granule progenitor
      organelles in mouse megakaryocytes.
AB  - Arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome is caused by
      deficiencies in the trafficking proteins VPS33B or VIPAR, and is associated with
      a bleeding diathesis and a marked reduction in platelet alpha-granules. We
      generated a tamoxifen-inducible mouse model of VPS33B deficiency, Vps33b(fl/fl)
      ER(T2), and studied the platelet phenotype and alpha-granule biogenesis.
      Ultrastructural analysis of Vps33b(fl/fl)-ER(T2) platelets identified a marked
      reduction in alpha-granule count and the presence of small granule-like
      structures in agreement with the platelet phenotype observed in ARC patients. A
      reduction of ~65% to 75% was observed in the alpha-granule proteins von
      Willebrand factor and P-selectin. Although platelet aggregation responses were
      not affected, a defect in delta-granule secretion was observed. Under arteriolar
      shear conditions, Vps33b(fl/fl)-ER(T2) platelets were unable to form stable
      aggregates, and tail-bleeding measurement revealed a bleeding diathesis. Analysis
      of bone marrow-derived megakaryocytes (MKs) by conventional and immuno-electron
      microscopy from Vps33b(fl/fl)-ER(T2) mice revealed a reduction in mature type-II
      multivesicular bodies (MVB II) and an accumulation of large vacuoles. Proteins
      that are normally stored in alpha-granules were underrepresented in MVB II and
      proplatelet extensions. These results demonstrate that abnormal protein
      trafficking and impairment in MVB maturation in MKs underlie the alpha-granule
      deficiency in Vps33b(fl/fl)-ER(T2) mouse and ARC patients. 

PMID- 25947944
TI  - Phase behavior of skin lipid mixtures: the effect of cholesterol on lipid
      organization.
AB  - The lipid matrix in the stratum corneum (SC), the upper layer of the skin, plays
      a critical role in the skin barrier. The matrix consists of ceramides (CERs),
      cholesterol (CHOL) and free fatty acids (FFAs). In human SC, these lipids form
      two coexisting crystalline lamellar phases with periodicities of approximately 6
      and 13 nm. In the studies reported here, we investigated the effect of CHOL on
      lipid organization in each of these lamellar phases separately. For this purpose,
      we used lipid model mixtures. Our studies revealed that CHOL is imperative for
      the formation of each of the lamellar phases. At low CHOL levels, the formation
      of the lamellar phases was dramatically changed: a minimum 0.2 CHOL level in the
      CER/CHOL/FFA (1 : 0.2 : 1) mixture is required for the formation of each of the
      lamellar phases. Furthermore, CHOL enhances the formation of the highly dense
      orthorhombic lateral packing. The gradual increment of CHOL increases the
      fraction of lipids forming the very dense orthorhombic lateral packing.
      Therefore, these studies demonstrate that CHOL is an indispensable component of
      the SC lipid matrix and is of fundamental importance for appropriate dense lipid
      organization and thus important for the skin barrier function. 

PMID- 25947945
TI  - Transparent oxides forming conductor/insulator/conductor heterojunctions for
      photodetection.
AB  - Photoexcited hot electrons from conductors can be injected into the conduction
      bands of wide-bandgap materials, thus enabling the visible and near-infrared
      (NIR) photoactivities of light-harvesting devices. While metals have been
      dominantly used as conductors to excite hot electrons, we demonstrate that
      transparent conductive oxides (TCOs) can also be used for this purpose. Trilayer
      structures consisting of a thin dielectric layer sandwiched by TCOs show
      photoresponsiveness in UV, visible, as well as NIR wavelength range. As these
      trilayer structures are transparent, they can be used to monitor light without
      blocking it. 

PMID- 25947946
TI  - Drug repositioning can accelerate discovery of pharmacological chaperones.
AB  - A promising strategy for the treatment of genetic diseases, pharmacological
      chaperone therapy, has been proposed recently. It exploits small molecules which
      can be administered orally, reach difficult tissues such as the brain and have
      low cost. This strategy has a vast field of application. In order to make drug
      development as fast as possible, it is important to exploit drug repositioning.
      We evaluated the impact and limitations of this approach for rare diseases and we
      provide a shortcut in finding drugs for off-target usage. 

PMID- 25947948
TI  - Assessment of Pharmacy Manpower and Services in New England.
AB  - OBJECTIVES: This study assessed longitudinal trends in pharmacy staffing and
      services in the 6 New England states by comparing survey results from 2008 and
      2013. METHODS: A validated 32-item survey was mailed in 2008 and 2013 to a random
      sample of 2000 pharmacists. Each sample represented approximately 15% (2008) and
      13% (2013) of the active rosters. RESULTS: Response rates were 24% in 2008 and
      23% in 2013. In all, 45% of 2013 respondents reported a pharmacist position
      vacancy in the past 12 months versus 62% in 2008. In all, 12% of 2013 respondents
      agreed or strongly agreed with a statement regarding pharmacists' shortage versus
      77% in 2008. Disease management services were reported to be offered by 23% of
      2013 respondents versus 28% in 2008. Reasons for not offering the services in
      2013 included the lack of staffing (61%), expertise (28%), and reimbursement
      (29%). In 2008, these results were 74%, 33%, and 31%, respectively. CONCLUSIONS:
      The pharmacist shortage within New England was alleviated during 2008 to 2013.
      Participation of pharmacists in disease management services did not follow
      staffing trends as fewer pharmacists reported providing services. Key barriers to
      services provision persist and consideration of how to resolve them (medication
      therapy management reimbursement and additional education) should be explored.

PMID- 25947949
TI  - Educating Pharmacists on a Prescription Drug Monitoring Program.
AB  - OBJECTIVE: To provide education to community pharmacists regarding the
      registration and use of the Texas prescription drug monitoring program (PDMP) and
      to assess the impact of the education on pharmacists' perceptions of the PDMP.
      METHOD: The study design was a descriptive, pre and post, cross-sectional survey
      conducted among community pharmacists attending a PDMP education program. The
      program was designed to present the PDMP as a public health tool available to
      assist pharmacists with dispensing decisions related to controlled prescription
      drugs. RESULTS: Of the 24 pharmacists who completed the survey, 23 were already
      registered to use the PDMP. However, all 23 felt that the program successfully
      educated users regarding the PDMP and agreed that other community pharmacists
      would benefit from the program presented. After the program, 14 participants
      responded they would very likely use the PDMP in the next 30 days. Recognition of
      the use of PDMPs as a program for both pharmacists and physicians was increased
      from 12.5% (pre) to 73.9% (post). CONCLUSION: Pharmacists found the educational
      program beneficial and they were very likely to use the PDMP in the future.
      Perceptions of the Texas PDMP were changed from pre- to post-education program,
      with recognition that a PDMP can be a beneficial tool for pharmacy practice.

PMID- 25947947
TI  - Reducing tumor growth and angiogenesis using a triple therapy measured with
      Contrast-enhanced ultrasound (CEUS).
AB  - BACKGROUND: To evaluate the in vivo response by detecting the anti-angiogenic and
      invasion-inhibiting effects of a triple-combination-therapy in an experimental
      small-animal-squamous-cell-carcinoma-model using the "flash-replenishment" (FR)
      method to assess tissue hemodynamics via contrast-enhanced-ultrasound (CEUS).
      METHODS: Human hypopharynx-carcinoma-cells were subcutaneously injected into the
      left flank of 22-female-athymic-nude-rats. After seven days of subcutaneous tumor
      growth, FR-measurements were performed on each rat. Treatment-group and control
      group were treated every day for a period of one week, with the treatment-group
      receiving solvents containing a triple therapy of Upamostat(r), Celecoxib(r) and
      Ilomastat(r) and the control-group solvents only. On day seven, follow-up
      measurements were performed using the same measurement protocol to assess the
      effects of the triple therapy. VueBox(r) was used to quantify the kinetic
      parameters and additional immunohistochemistry analyses were performed for
      comparison with and validation of the CEUS results against established methods
      (Proliferation/Ki-67, vascularization/CD31, apoptosis/caspase3). RESULTS:
      Compared to the control-group, the treatment-group that received the triple
      therapy resulted in a reduction of tumor growth by 48.6% in size. Likewise, the
      immunohistochemistry results showed significant decreases in tumor proliferation
      and vascularization in the treatment-group in comparison to the control-group of
      26%(p <= 0.05) and 32.2%(p <= 0.05) respectively. Correspondingly, between the
      baseline and follow-up measurements, the therapy-group was associated with a
      significant(p <= 0.01) decrease in the relative-Blood-Volume(rBV) in both the
      whole tumor(wt) and hypervascular tumor(ht) areas (p <= 0.01), while the control
      group was associated with a significant (p <= 0.01) increase of the rBV in the wt
      area and a non-significant increase (p <= 0.16) in the ht area. The mean-transit
      time (mTT) of the wt and the ht areas showed a significant increase (p <= 0.01)
      in the follow-up measurements in the therapy group. CONCLUSION: The triple
      therapy is feasible and effective in reducing both tumor growth and
      vascularization. In particular, compared with the placebo-group, the triple
      therapy-group resulted in a reduction in tumor growth of 48.6% in size when
      assessed by CEUS and a significant reduction in the number of vessels in the
      tumor of 32% as assessed by immunohistochemistry. As the immunohistochemistry
      supports the CEUS findings, CEUS using the "flash replenishment"(FR) method
      appears to provide a useful assessment of the anti-angiogenic and invasion
      inhibiting effects of a triple combination therapy.

PMID- 25947950
TI  - Detection and quantification of microRNA in cerebral microdialysate.
AB  - BACKGROUND: Secondary brain injury accounts for a major part of the morbidity and
      mortality in patients with spontaneous aneurysmal subarachnoid hemorrhage (SAH),
      but the pathogenesis and pathophysiology remain controversial. MicroRNAs (miRNAs)
      are important posttranscriptional regulators of complementary mRNA targets and
      have been implicated in the pathophysiology of other types of acute brain injury.
      Cerebral microdialysis is a promising tool to investigate these mechanisms. We
      hypothesized that miRNAs would be present in human cerebral microdialysate.
      METHODS: RNA was extracted and miRNA profiles were established using high
      throughput real-time quantification PCR on the following material: 1)
      Microdialysate sampled in vitro from A) a solution of total RNA extracted from
      human brain, B) cerebrospinal fluid (CSF) from a neurologically healthy patient,
      and C) a patient with SAH; and 2) cerebral microdialysate and CSF sampled in vivo
      from two patients with SAH. MiRNAs were categorized according to their relative
      recovery (RR) and a pathway analysis was performed for miRNAs exhibiting a high
      RR in vivo. RESULTS: Seventy-one of the 160 miRNAs detected in CSF were also
      found in in vivo microdialysate from SAH patients. Furthermore specific miRNAs
      consistently exhibited either a high or low RR in both in vitro and in vivo
      microdialysate. Analysis of repeatability showed lower analytical variation in
      microdialysate than in CSF. CONCLUSIONS: MiRNAs are detectable in cerebral
      microdialysate; a large group of miRNAs consistently showed a high RR in cerebral
      microdialysate. Measurement of cerebral interstitial miRNA concentrations may aid
      in the investigation of secondary brain injury in neurocritical conditions.

PMID- 25947951
TI  - Stochasticity, periodicity and localized light structures in partially mode
      locked fibre lasers.
AB  - Physical systems with co-existence and interplay of processes featuring distinct
      spatio-temporal scales are found in various research areas ranging from studies
      of brain activity to astrophysics. The complexity of such systems makes their
      theoretical and experimental analysis technically and conceptually challenging.
      Here, we discovered that while radiation of partially mode-locked fibre lasers is
      stochastic and intermittent on a short time scale, it exhibits non-trivial
      periodicity and long-scale correlations over slow evolution from one round-trip
      to another. A new technique for evolution mapping of intensity autocorrelation
      function has enabled us to reveal a variety of localized spatio-temporal
      structures and to experimentally study their symbiotic co-existence with
      stochastic radiation. Real-time characterization of dynamical spatio-temporal
      regimes of laser operation is set to bring new insights into rich underlying
      nonlinear physics of practical active- and passive-cavity photonic systems. 

PMID- 25947952
TI  - Late-onset severe chronic active EBV in a patient for five years with mutations
      in STXBP2 (MUNC18-2) and PRF1 (perforin 1).
AB  - Severe chronic active Epstein-Barr virus (CAEBV) disease is defined as a severe
      progressive illness lasting 6 months or longer with infiltration of tissues with
      EBV-positive lymphocytes, markedly elevated levels of EBV DNA in the blood, and
      no known immunodeficiency such as HIV. These patients usually have fever,
      splenomegaly, lymphadenopathy, and may have markedly elevated EBV antibody titers
      to viral capsid antigen. Although the cause of most cases of severe CAEBV is
      unknown, one well-documented case was associated with compound heterozygous
      mutations in PRF1 (perforin 1). Here we report a patient with prolonged severe
      CAEBV who underwent bone marrow transplant for his disease and subsequently was
      found to have compound heterozygous mutations in STXBP2 (MUNC18-2) as well as a
      heterozygous mutation in PRF1 (perforin 1). 

PMID- 25947953
TI  - Bilingual Text Messaging Translation: Translating Text Messages From English Into
      Spanish for the Text4Walking Program.
AB  - BACKGROUND: Hispanic adults in the United States are at particular risk for
      diabetes and inadequate blood pressure control. Physical activity improves these
      health problems; however Hispanic adults also have a low rate of recommended
      aerobic physical activity. To address improving physical inactivity, one area of
      rapidly growing technology that can be utilized is text messaging (short message
      service, SMS). A physical activity research team, Text4Walking, had previously
      developed an initial database of motivational physical activity text messages in
      English that could be used for physical activity text messaging interventions.
      However, the team needed to translate these existing English physical activity
      text messages into Spanish in order to have culturally meaningful and useful text
      messages for those adults within the Hispanic population who would prefer to
      receive text messages in Spanish. OBJECTIVE: The aim of this study was to
      translate a database of English motivational physical activity messages into
      Spanish and review these text messages with a group of Spanish speaking adults to
      inform the use of these text messages in an intervention study. METHODS: The
      consent form and study documents, including the existing English physical
      activity text messages, were translated from English into Spanish, and received
      translation certification as well as Institutional Review Board approval. The
      translated text messages were placed into PowerPoint, accompanied by a set of
      culturally appropriate photos depicting barriers to walking, as well as walking
      scenarios. At the focus group, eligibility criteria for this study included being
      an adult between 30 to 65 years old who spoke Spanish as their primary language.
      After a general group introduction, participants were placed into smaller groups
      of two or three. Each small group was asked to review a segment of the translated
      text messages for accuracy and meaningfulness. After the break out, the group was
      brought back together to review the text messages. RESULTS: A translation
      confirmation group met at a church site in an urban community with a large
      population of Hispanics. Spanish speaking adults (N=8), with a mean age of 40 (SD
      6.3), participated in the study. Participants were engaged in the group and
      viewed the text messages as culturally appropriate. They also thought that text
      messages could motivate them to walk more. Twenty-two new text messages were
      added to the original database of 246 translated text messages. While the text
      messages were generally understood, specific word preferences were seen related
      to personal preference, dialect, and level of formality which resulted in minor
      revisions to four text messages. CONCLUSIONS: The English text messages were
      successfully translated into Spanish by a bilingual research staff and reviewed
      by Hispanic participants in order to inform the use of these text messages for
      future intervention studies. These Spanish text messages were recently used in a
      Text4Walking intervention study.

PMID- 25947955
TI  - What's new in vasopressin?

PMID- 25947957
TI  - Roundtable discussion on the Third Global Symposium on Health Systems Research:
      why prioritise talk over aid in the midst of the Ebola crisis?
AB  - Health systems experts from around the world discuss why they were meeting at the
      Third Global Symposium on Health Systems Research while people were dying of
      Ebola in West Africa. 

PMID- 25947959
TI  - Graphene opens up to new applications.

PMID- 25947956
TI  - Cardiometabolic risk factors in young adults who were born preterm.
AB  - Adults who were born preterm with a very low birth weight have higher blood
      pressure and impaired glucose regulation later in life compared with those born
      at term. We investigated cardiometabolic risk factors in young adults who were
      born at any degree of prematurity in the Preterm Birth and Early Life Programming
      of Adult Health and Disease (ESTER) Study, a population-based cohort study of
      individuals born in 1985-1989 in Northern Finland. In 2009-2011, 3 groups
      underwent clinical examination: 134 participants born at less than 34 gestational
      weeks (early preterm), 242 born at 34-36 weeks (late preterm), and 344 born at 37
      weeks or later (controls). Compared with controls, adults who were born preterm
      had higher body fat percentages (after adjustment for sex, age, and cohort (1985
      1986 or 1987-1989), for those born early preterm, difference = 6.2%, 95%
      confidence interval (CI): 0.4, 13.2; for those born late preterm, difference =
      8.0%, 95% CI: 2.4, 13.8), waist circumferences, blood pressure (for those born
      early preterm, difference = 3.0 mm Hg, 95% CI: 0.9, 5.1; for those born late
      preterm, difference = 1.7, 95% CI: -0.1, 3.4), plasma uric acid levels (for those
      born early preterm, difference = 20.1%, 95% CI: 7.9, 32.3; for those born late
      preterm, difference = 20.2%, 95% CI: 10.7, 30.5), alanine aminotransferase
      levels, and aspartate transaminase levels. They were also more likely to have
      metabolic syndrome (for those born early preterm, odds ratio = 3.7, 95% CI: 1.6,
      8.2; for those born late preterm, odds ratio = 2.5, 95% CI: 1.2, 5.3). Elevated
      levels of conventional and emerging risk factors suggest a higher risk of
      cardiometabolic disease later in life. These risk factors are also present in the
      large group of adults born late preterm. 

PMID- 25947961
TI  - Nanoporous graphene: Membranes at the limit.

PMID- 25947958
TI  - Maternal molecular hydrogen treatment attenuates lipopolysaccharide-induced rat
      fetal lung injury.
AB  - Maternal inflammation is associated with spontaneous preterm birth and
      respiratory impairment among premature infants. Recently, molecular hydrogen (H2)
      has been reported to have a suppressive effect on oxidative stress and
      inflammation. The aim of this study was to evaluate the effects of H2 on fetal
      lung injury caused by maternal inflammation. Cell viability and the production of
      interleukin-6 (IL-6) and reactive oxygen species (ROS) were examined by treatment
      with lipopolysaccharide (LPS) contained in ordinal or H2-rich medium (HM) using a
      human lung epithelial cell line, A549. Pregnant Sprague Dawley rats were divided
      into three groups: Control, LPS, and HW + LPS groups. Rats were injected with
      phosphate-buffered saline (Control) or LPS intraperitoneally (LPS) on gestational
      day 19 and provided H2 water (HW) ad libitum for 24 h before LPS injection (HW +
      LPS). Fetal lung samples were collected on day 20, and the levels of apoptosis,
      oxidative damage, IL-6, and vascular endothelial growth factor (VEGF) were
      evaluated using immunohistochemistry. The number of apoptotic cells, and levels
      of ROS and IL-6 were significantly increased by LPS treatment, and repressed
      following cultured with HM in A549 cells. In the rat models, the population
      positive for cleaved caspase-3, 8-hydroxy-2'-deoxyguanosine, IL-6, and VEGF was
      significantly increased in the LPS group compared with that observed in the
      Control group and significantly decreased in the HW + LPS group. In this study,
      LPS administration induced apoptosis and oxidative damage in fetal lung cells
      that was ameliorated by maternal H2 intake. Antenatal H2 administration may
      decrease the pulmonary mobility associated with inflammation in premature
      infants. 

PMID- 25947962
TI  - 2D materials: Memristor goes two-dimensional.

PMID- 25947963
TI  - Metal-halide perovskites for photovoltaic and light-emitting devices.
AB  - Metal-halide perovskites are crystalline materials originally developed out of
      scientific curiosity. Unexpectedly, solar cells incorporating these perovskites
      are rapidly emerging as serious contenders to rival the leading photovoltaic
      technologies. Power conversion efficiencies have jumped from 3% to over 20% in
      just four years of academic research. Here, we review the rapid progress in
      perovskite solar cells, as well as their promising use in light-emitting devices.
      In particular, we describe the broad tunability and fabrication methods of these
      materials, the current understanding of the operation of state-of-the-art solar
      cells and we highlight the properties that have delivered light-emitting diodes
      and lasers. We discuss key thermal and operational stability challenges facing
      perovskites, and give an outlook of future research avenues that might bring
      perovskite technology to commercialization. 

PMID- 25947964
TI  - Creativity unleashed.

PMID- 25947965
TI  - Risk stratification for sudden death in arrhythmogenic right ventricular
      cardiomyopathy.
AB  - Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC) is an uncommon
      but increasingly recognized inherited cardiomyopathy that is associated with
      malignant ventricular arrhythmias and sudden cardiac death, particularly in young
      individuals. The implantable cardioverter-defibrillator (ICD) is widely regarded
      as the only treatment modality with evidence to support improved survival in
      patients with ARVC and secondary prevention indications. In contrast, there is no
      universally accepted risk stratification scheme to guide ICD therapy for primary
      prevention against sudden cardiac death. Potential benefits must be weighed
      against the considerable risks of complications and inappropriate shocks in this
      young patient population. This article tackles the challenges of risk
      stratification for sudden cardiac death in ARVC and critically appraises
      available evidence for various proposed risk factors. The authors' over-arching
      objective is to provide the clinician with evidence-based guidance to inform
      decisions regarding the selection of appropriate candidates with ARVC for ICD
      therapy. 

PMID- 25947967
TI  - Lithium as a rescue therapy for regression and catatonia features in two SHANK3
      patients with autism spectrum disorder: case reports.
AB  - BACKGROUND: Phelan-Mc Dermid syndrome is a contiguous disorder resulting from
      22q13.3 deletion implicating the SHANK3 gene. The typical phenotype includes
      neonatal hypotonia, moderate to severe intellectual disability, absent or delayed
      speech, minor dysmorphic features and autism or autistic-like behaviour.
      Recently, point mutations or micro-deletions of the SHANK3 gene have been
      identified, accompanied by a phenotype different from the initial clinically
      description in Phelan McDermid syndrome. CASE PRESENTATION: Here we present two
      case studies with similar psychiatric and genetic diagnosis as well as similar
      clinical history and evolution. The two patients were diagnosed with autism
      spectrum disorders in childhood and presented regression with catatonia features
      and behavioural disorders after a stressful event during adolescence.
      Interestingly, both patients presented mutation/microdeletion of the SHANK3 gene,
      inducing a premature stop codon in exon 21. Different pharmacological treatments
      (antipsychotics, benzodiazepines, mood stabilizer drugs, antidepressants, and
      methylphenidate) failed to improve clinical symptoms and lead to multiple adverse
      events. In contrast, lithium therapy reversed clinical regression, stabilized
      behavioural symptoms and allowed patients to recover their pre-catatonia level of
      functioning, without significant side effects. CONCLUSION: These cases support
      the hypothesis of a specific SHANK3 phenotype. This phenotype might be linked to
      catatonia-like deterioration for which lithium use could be an efficient
      treatment. Therefore, these cases provide an important contribution to the field
      of autism research, clinical genetics and possible pharmacological answers.

PMID- 25947968
TI  - Cultural significance of wild mammals in Mayan and mestizo communities of the
      Lacandon Rainforest, Chiapas, Mexico.
AB  - BACKGROUND: Several ethnobiology studies evaluate the cultural significance (CS)
      of plants and mushrooms. However, this is not the case for mammals. It is
      important to make studies of CS allowing the comparison of cultural groups
      because the value given to groups of organisms may be based on different
      criteria. Such information would be valuable for wildlife preservation plans. In
      this study, the most culturally significant species of mammals from the Lacandon
      Rainforest (Chiapas, Mexico) for people from two Mayan-Lacandon and mestizo
      communities were identified. The reasons behind the CS of the studied species
      were explored and the existence of differences among the cultural groups was
      evaluated. METHODS: One hundred ninety-eight semi-structured and structured
      interviews were applied to compile socio-demographic information, qualitative
      data on CS categories, and free listings. Frequency of mention was a relative
      indicator to evaluate the CS of each species of mammal. Comparison of responses
      between communities was carried out through multivariate analyses. The non
      parametric Mann-Whitney U test was used to compare the number of mentioned
      species by Lacandons and mestizos as well as different responses in the
      qualitative categories. A chi2 test was used to compare frequency of categories.
      RESULTS: 38 wild mammal species were identified. The classification and Principal
      Components Analyses show an apparent separation between Lacandon and mestizo
      sites based on the relative importance of species. All four communities mentioned
      the lowland paca the most, followed by peccary, white-tailed deer, armadillo, and
      jaguar. No significant difference was found in the number of mentioned species
      between the two groups. Eight CS categories were identified. The most important
      category was "harmful mammals", which included 28 species. Other relevant
      categories were edible, medicinal, and appearing in narratives. CONCLUSIONS: The
      data obtained in this study demonstrates the existence of differential cultural
      patterns in the relationships that Lacandon and mestizo groups establish with
      mammals. Species are deemed important either because they are eaten of because of
      the harm they cause. We suggest the incorporation of local conceptions about wild
      animals in conservation frameworks for the fauna in the Lacandon Rainforest.

PMID- 25947971
TI  - The cover page.

PMID- 25947970
TI  - Effect of iron plaque on antimony uptake by rice (Oryza sativa L.).
AB  - Although iron (Fe) plaque has been shown to significantly affect the uptake of
      toxic antimony (Sb) by rice, knowledge about the influence of iron plaque on
      antimony (Sb) (amount, mechanisms, etc) is, however, limited. Here, the effect of
      Fe plaque on Sb(III) and Sb(V) (nominal oxidation states) uptake by rice (Oryza
      sativa L.) was investigated using hydroponic experiments and synchrotron-based
      techniques. The results showed that iron plaque immobilized Sb on the surface of
      rice roots. Although the binding capacity of iron plaque for Sb(III) was markedly
      greater than that for Sb(V), significantly more Sb(III) was taken up by roots and
      transported to shoots. In the presence of Fe plaque, Sb uptake into rice roots
      was significantly reduced, especially for Sb(III). However, this did not
      translate into decreasing Sb concentrations in rice shoots and even increased
      shoot Sb concentrations during high Fe-Sb(III) treatment. 

PMID- 25947972
TI  - My serendipitous move to neurosurgery.

PMID- 25947973
TI  - Scrub typhus.

PMID- 25947974
TI  - Giant aneurysms: Still in the quest of a perfect cure.

PMID- 25947976
TI  - Treatment of giant intracranial aneurysms: What is the best option?

PMID- 25947975
TI  - Surgical management of giant intracranial aneurysms: A neurosurgeon's
      perspective.

PMID- 25947977
TI  - Distribution of neurologists and neurosurgeons in India and its relevance to the
      adoption of telemedicine.
AB  - Majority of Indians have no access to centres of neurological excellence in the
      country. A detailed analysis of 3666 members of the Neurological Society of India
      and the Indian Academy of Neurology revealed that not a single member lived in a
      geographical area covering 934.8 million people. 30.09% live in the four major
      metropolitan cities, 29.54% in the state capitals, 30.58% in Tier 2 cities, 7.12%
      in tier 3 cities and 2.67% in rural areas covering a population of 84.59 million.
      Building additional neurological centres cannot be the only answer, given the
      acute shortage of funds and trained personnel. In 1999, the author among others,
      foresaw that it could be possible, to extend the reach of urban specialists to
      suburban and rural India, by virtual means. The neurological community has been
      slow to use Information and Communication Technology (ICT) as an integral part of
      their health care delivery system. This article analyses the distribution of
      neurologists and neurosurgeons in India and suggests that providing additional
      virtual neurological care can be the only answer to offset the lop sided
      distribution of clinical care givers in neurosciences. In this article, the
      authors' considerable experience in introducing and developing telehealth in
      India over the last 15 years is being shared with specific emphasis on its
      relevance to neurosciences. A review of the global literature on telemedicine and
      neurosciences will substantiate the plea that telemedicine must be deployed by
      neurologists and neurosurgeons in India to extend their reach to patients
      particularly those residing in rural areas. 

PMID- 25947978
TI  - delta-Aminolevulinic acid-induced fluorescence-guided resection of brain tumors.
AB  - Maximal resection of gliomas is the current standard of care. Various technical
      adjuncts facilitate this. Aminolevulinic acid (ALA)-induced fluorescence guided
      resection (FGR) is one such strategy. We review the current literature related to
      ALA FGR. It is based on the selective uptake of ALA into glioma cells and its
      preferential conversion to protoporphyrin IX. This selectivity provides a high
      positive predictive value for ALA induced fluorescence. Since the introduction of
      this technique, clinical experience supports its efficacy in improving resections
      in malignant gliomas when compared to other contemporary intraoperative imaging
      strategies such as the magnetic resonance imaging (MRI) or the adjuncts that
      exhibit passive permeability like fluorescein. Future research into the
      understanding of the basis of ALA metabolism in glioma cells and advances in
      visualization technology will potentially improve the scope of application of
      this technique. 

PMID- 25947979
TI  - Non-motor symptoms in an Indian cohort of Parkinson's disease patients and
      correlation of progression of non-motor symptoms with motor worsening.
AB  - AIM: To document the frequency and prevalence of non-motor symptoms (NMS) in an
      Indian cohort of Parkinson's disease (PD) patients. OBJECTIVES: To validate the
      non-motor score scale (NMSS) in an Indian cohort of PD patients for recording NMS
      of the disease, to study the prevalence and frequency of NMS in Indian PD
      patients using the NMSS, and to compare the progression of NMS with motor
      worsening. Conclusion and Results: This was a cross-sectional, single-center,
      open-label, one point in time evaluation study conducted from 2009 to 2011. It
      validated the NMSS scale in an Indian population. The study has profiled the
      prevalence and pattern of NMS in an Indian cohort of PD patients. Comparison of
      NMS scale scores with the Unified PD Rating Scale motor scores demonstrated a
      correlation between non-motor and motor symptoms in the disease progression,
      particularly of manifestations related to the cognitive decline, memory
      disturbances, urinary incontinence and smell.

PMID- 25947980
TI  - Decompressive craniectomy in traumatic brain injury: A single-center,
      multivariate analysis of 1,236 patients at a tertiary care hospital in India.
AB  - OBJECT: To evaluate the outcome of patients undergoing a decompressive
      craniectomy (DC) in traumatic brain injury (TBI) and the factors predicting
      outcome. MATERIALS AND METHODS: A total of 1,236 patients with TBI operated with
      a DC from January 2008 to December 2013 at a tertiary care hospital were included
      in the study. The data from the hospital computerized database was
      retrospectively analyzed and 324 (45%) patients were followed-up for a mean
      duration of 25.3 months (range 3-42 months) among the cohort of 720 alive
      patients. The institute's ethical committee clearance was obtained before the
      start of the study. RESULTS: There were 81% males with a median age
      [interquartile range (IQR)] of 32 (23-45) years. The mortality rate and median
      (IQR) Glasgow outcome score (GOS) at discharge in patients presenting with minor,
      moderate, and severe head injury were 18%, 5 (4-5); 28%, 4 (1-5); and 47.4%, 2 (1
      4), respectively. An overall favorable outcome (GOS 4 and 5) at discharge was
      observed in 46.5% patients and in 39% patients who presented with severe TBI.
      Only 7.5% patients were in a persistent vegetative state (PVS), while 78% had an
      overall favorable outcome at the last follow-up of surviving patients (P <
      0.001). On multivariate analysis, the factors predictive of a favorable GOS at
      discharge were: a younger age (odds ratio (OR) 1.03, confidence interval (CI) =
      1.02-1.04; P < 0.001), no pupillary abnormalities at admission (OR 2.28, CI =
      1.72-3.02; P < 0.001), absence of preoperative hypotension (OR 1.91, CI = 1.08
      3.38; P = 0.02), an isolated TBI (OR 1.42, CI = 1.08-1.86; P = 0.01), absence of
      a preoperative infarct (OR 3.68, CI = 1.74-7.81; P = 0.001), presence of a minor
      head injury (OR 6.33, CI = 4.07-9.86; P < 0.001), performing a duraplasty (OR
      1.86, CI = 1.20-2.87; P = 0.005) rather than a slit durotomy (OR 3.95, CI = 1.67
      9.35; P = 0.002), and, avoidance of a contralateral DC (OR 3.58, CI = 1.90-6.73;
      P < 0.001). CONCLUSIONS: The severity of head injury, performing a duraplasty
      rather than a slit durotomy, avoidance of a contralateral DC, and the presence of
      preoperative hypotension, infarct, and/or pupillary asymmetry have the highest
      odds of predicting the short term GOS at the time of discharge, after a DC in
      patients with TBI. Although DC carries a high risk of mortality, the probability
      of the survivors having a favorable outcome is significantly more as compared to
      those who remain in a PVS.

PMID- 25947981
TI  - Endovascular management of giant aneurysms: An introspection.
AB  - AIMS: To evaluate the outcome of giant intra-dural aneurysms managed with
      endovascular techniques. MATERIALS AND METHODS: We retrospectively reviewed a
      series of 39 consecutive giant intra-dural aneurysms. The technical feasibility
      of endovascular treatment, its complications, the angiographic results and the
      clinical outcome were assessed. Logistic regression analysis was performed to
      evaluate for predictors of a poor outcome. RESULTS: Nine patients were left
      untreated. During a 30 month follow-up, four of them (44.4%) died and two (22.2%)
      deteriorated. Thirty aneurysms (12 located in the anterior circulation and 18
      located in the posterior circulation) were treated using endovascular methods. Of
      these, 11 were treated by parent vessel occlusion, 11 by stent-assisted coiling,
      one using only coils, six using solely a stent, and, one using both coils and
      onyx. During a 28 month follow-up, seven (23.3%) patients died and two (6.7%)
      patients experienced permanent neurological deficits. The mortality and morbidity
      in the endovascular group seemed lower than that in the untreated group (P =
      0.045, 30% vs. 66.7%). There was no difference in the results of endovascular
      treatment between giant intra-dural aneurysms located in the posterior and the
      anterior circulation. CONCLUSIONS: Giant intra-dural aneurysms, whether treated
      or not, may have a poor clinical outcome. The outcome following endovascular
      treatment of these lesions is better than its natural history when left
      untreated. However, endovascular treatment may often be associated with high
      complication rates and a low chance of cure.

PMID- 25947982
TI  - Cytokines, MMP-2, and MMP-9 levels in patients with a solitary cysticercus
      granuloma.
AB  - OBJECTIVES: In patients with neurocysticercosis, perilesional inflammatory
      activity is thought to be responsible for seizures. This study was designed to
      evaluate the serum and cerebrospinal fluid (CSF) concentrations of cytokines as
      well as matrix metalloproteinase (MMP)-2 and MMP-9 in patients with a solitary
      cysticercus granuloma. MATERIALS AND METHODS: The study included 47 patients
      suffering from seizures in whom a solitary cysticercus granuloma was detected on
      a computed tomography (CT) scan. The study also included 47 control subjects.
      Their serum and cerebrospinal fluid (CSF) was analysed for cytokines and MMP
      levels. A follow-up CT was performed after 6 months. RESULTS: The median levels
      of cytokines, interleukin (IL)-1beta, IL-5, IL-6, IL-10 and tissue necrosis
      factor (TNF)-alpha, MMP-2 and MMP-9 were significantly elevated, both in the
      serum and CSF of patients having an intracerebral solitary cysticercus granuloma,
      in comparison to that of controls. The follow-up CT revealed that in 27 patients,
      the lesions were calcified and in 5 patients, there was complete resolution of
      the lesions. In 15 patients, the lesions remained unchanged. Higher baseline CSF
      MMP-2 and TNF-alpha level were seen in patients with persisting lesions. Higher
      serum baseline MMP-2, IL-6 and a low CSF IL-10 level were seen in patients with
      complete resolution of the granuloma. A high baseline IL-1beta level was
      associated with a calcified lesion. Fourteen patients had recurrence of seizures.
      A high baseline serum TNF-alpha level was independently associated with seizure
      recurrence (P = 0.021, OR = 1.041, CI = 1.006 to 1.078). CONCLUSION: In patients
      with a solitary cysticercus granuloma, cytokines and matrix metalloproteinases in
      the CSF and serum are elevated. Different patterns of immunological changes were
      observed in patients following resolution or calcification of the lesion.

PMID- 25947983
TI  - Is acetazolamide really useful in the management of traumatic cerebrospinal fluid
      rhinorrhea?
AB  - BACKGROUND: Traumatic cerebrospinal fluid (CSF) rhinorrhea is a serious and
      potentially fatal condition as it may lead to meningitis. As acetazolamide
      decreases CSF production and hence CSF pressure, it has been proposed that the
      medication may help in curing CSF rhinorrhea. There is no definitive evidence,
      however, that acetazolamide is actually beneficial in treating traumatic CSF
      rhinorrhea. The aim of this study was to determine if the administration of
      acetazolamide in patients of head trauma with CSF rhinorrhea was beneficial in
      decreasing the duration of CSF rhinorrhea. The acid-base and electrolyte changes
      caused by the drug were also studied. MATERIALS AND METHODS: We conducted a
      single center randomized prospective study. Forty-four patients of head trauma
      with CSF rhinorrhea were divided into two groups, the experimental group (21
      patients) was given acetazolamide; and, the control group (23 patients) did not
      receive the medication. The median duration of CSF leak in days, and the
      electrolyte changes observed on administration of the medication were recorded in
      both the groups. RESULTS: Both the experimental and control groups were well
      matched in terms of age, sex, mechanism of injury, Glasgow Coma Scale (GCS) and
      the type of skull fracture. The median duration of CSF leak in the control group
      was of 4 days and in the study group, of 5 days. Acetazolamide caused significant
      metabolic acidosis and hypokalemia (as shown by decreased serum pH, serum
      bicarbonate and serum potassium levels) in the experimental group when compared
      to the control group. CONCLUSIONS: Acetazolamide did not influence the resolution
      of traumatic CSF rhinorrhea and instead lead to significant metabolic and
      electrolyte disturbances.

PMID- 25947984
TI  - Critical appraisal of serum phenytoin variation with patient characteristics in a
      North Indian population.
AB  - CONTEXT: Phenytoin (PHT) is one of the frontrunner drugs used as monotherapy in
      the management of epilepsy. It is also one of the most common drugs causing
      adverse drug reactions (ADRs). The aim of this study was to study the
      relationship between serum PHT levels and the age, gender, dosage and genetic
      polymorphisms in a North Indian population. This knowledge will help in devising
      drug dosage schedules in various sub-groups of patients as well as in reducing
      its ADRs. MATERIALS AND METHODS: A retrospective analysis of data of 6224
      patients from 1998 to 2009 receiving PHT alone for greater than (>) 4 weeks was
      performed. Patients suspected of being non-compliant, being overdosed or having a
      hepatic or renal disorder were excluded from the study. Two thousand eight
      hundred and eighty-eight patients fulfilling the inclusion criteria were divided
      into three groups: children (1-18 years), adults (19-60 years) and elderly (>60
      years). RESULTS: There was a male preponderance (80%) in all the groups. A
      significant difference was found in the mean dose between children and adults as
      well as between children and elderly (P = 0.00). Also, there was a significant
      difference in the mean concentration and dose ratio between children and adults
      (P = 0.00). However, a negative correlation was observed between the daily dose
      and dose ratio (r = -0.36, P = 0.00) that was highest (r = -0.58, P = 0.00) in
      the elderly. There was a significant gender difference in the mean dose in both
      children (P = 0.03) and adults (P = 0.00), whereas the mean concentration
      differed in adults only. Every fifth patient was an intermediate metabolizer (IM)
      (CYP2C9FNx011/FNx013) and showed higher steady state drug levels (>17 mg/L)
      compared with extensive metabolizers (EMs) (<12 mg/L). The genetic difference
      between IM and EM was more prevalent in the dose ratio at maintenance dose, with
      a mean +/- SD of 4.041 +/- 1.288 mg/L/mg/kg in nine patients carrying the
      CYP2C9FNx011/FNx013 genotype compared with 2.145 +/- 0.817 mg/L/mg/kg in 26
      patients carrying the CYP2C9FNx011/FNx011 genotype (P = 0.00). CONCLUSION: North
      Indian female children and male adults frequently attain a higher serum
      concentration with the same dose when compared to the other groups. Absence of
      poor metabolizers may be responsible for a lower number of cases exhibiting
      toxicity in our population; however, this needs elucidation in a larger number of
      patients.

PMID- 25947985
TI  - Scrub typhus meningitis: An under-recognized cause of aseptic meningitis in
      India.
AB  - BACKGROUND: Central nervous system (CNS) involvement in scrub typhus is seen in
      up to a quarter of patients. However, the literature on cerebrospinal fluid (CSF)
      analysis and outcome in meningitis/meningo-encephalitis due to scrub typhus is
      scant. MATERIALS AND METHODS: This retrospective study included patients who were
      admitted to a medical college hospital with scrub typhus meningitis/meningo
      encephalitis between 2005 and 2011. The clinical and laboratory profile, details
      of CSF analysis and outcome were documented. RESULTS: The study included 189
      patients with meningitis/meningo-encephalitis due to scrub typhus. The mean age
      of the patients was 41 +/- 4 years. The mean duration of fever before
      presentation was 9.4 +/- 3 days. The common presenting complaints were headache
      (64.2%), nausea/vomiting (60%), altered sensorium (53.7%) and seizures (22.1%).
      The presence of an eschar was documented in 27.5% of the patients. The mean CSF
      white blood count was 80 cells/cu mm (range: 5-740). There was a clear lymphocyte
      predominance (mean 87.6%). The mean CSF protein level was 105 mg% (range: 13
      640). The mean CSF sugar level was 63.9 mg% (range 25-350), and was less than 40
      mg% in 11.1% of the cases. The case fatality rate was 5.8% (11/189). Univariate
      analysis showed the presence of an eschar (15.4% vs 2.2%; Odds Ratio [OR]: 8.1)
      and altered sensorium (9.8% vs 1.1%; OR: 9.2) to be significant predictors of
      mortality. CONCLUSIONS: In endemic regions, scrub typhus should be considered in
      the differential diagnosis of aseptic meningitis. Modest elevation of cells in
      the CSF with lymphocytic pleocytosis and multi-organ involvement may indicate
      scrub typhus meningitis/meningo-encephalitis.

PMID- 25947986
TI  - Genetic analysis of a Chinese family provides further evidence for linkage of
      familial cortical myoclonic tremor with epilepsy to 5p15.31-p15.
AB  - AIM: In this study, we genotyped eight microsatellite markers on chromosome 5 and
      performed linkage analyses. We aimed to establish the pathogenic gene loci in
      this familial cortical myoclonic tremor with epilepsy (FCMTE) pedigree. MATERIALS
      AND METHODS: Reliable clinical information was obtained on the Chinese family
      members. Our study performed linkage analysis across these loci to identify and
      further characterize the pathogenic gene locus underlying FCMTE in Chinese
      patients. RESULTS: Positive signals (>1) were only obtained for 5p15.31-p15
      (Logarithm of Odds (LOD) values 2.16 and 1.34 for D5S1957 and D5S2095,
      respectively; theta =0.0), supporting involvement of this region in the FCTME
      pedigree analyzed. CONCLUSION: Genetic analysis of a Chinese family provides
      further evidence for linkage of FCMTE to 5p15.31-p15.

PMID- 25947987
TI  - Citrin deficiency: A treatable cause of acute psychosis in adults.
AB  - Citrin deficiency is an autosomal recessive genetic disorder caused by a defect
      in the mitochondrial aspartate/glutamate antiporter, citrin. The disorder
      manifests either as neonatal intra-hepatic cholestasis or occurs in adulthood
      with recurrent hyperammonemia and neuropsychiatric disturbances. It has a high
      prevalence in the East Asian population, but is actually pan-ethnic. We report
      the case of a 26-year-old male patient presenting with episodes of abnormal neuro
      psychiatric behavior associated with hyperammonemia, who was diagnosed to be
      having citrin deficiency. Sequencing of the SLC25A13 gene revealed two novel
      mutations, a single base pair deletion, c. 650delT (p.Phe217SerfsFNx0133) in exon
      7, and a missense mutation, c. 869T>C (p.Ile290Thr) in exon 9. Confirmation of
      the diagnosis allowed establishment of the appropriate management. The latter is
      an essential pre-requisite for obtaining a good prognosis as well as for family
      counseling. 

PMID- 25947989
TI  - A 58-year-old lady with progressive neurological syndrome: Presence of an
      intravascular lymphoma.

PMID- 25947988
TI  - Six-level isolated spinous process fracture of the thoracic vertebrae (clay
      shoveler's fracture) and a review of the literature.
AB  - Clay-shoveler's fractures are isolated, avulsion-type spinous process fractures
      of the lower cervical and upper thoracic vertebrae. Multi-level fractures of the
      spinous processes are extremely rare. We report the case of a 60-year-old female
      patient with a six-level isolated spinous process fracture of the thoracic spine.
      Our case is the fourth reported case in literature, of an isolated spinous
      process fracture involving five or more levels in the thoracic vertebrae. 

PMID- 25947990
TI  - Unilateral hemilaminectomy: The surgical approach of choice for juxta-medullary
      spinal tumors.
AB  - BACKGROUND: The conventional laminectomy may precipitate numerous long-term
      complications such as the development of kypho-scoliosis, spinal instability,
      epidural fibrosis and loss of bony shield over the spinal cord, thus increasing
      the risk of a subsequent myelopathy. The present study evaluates the efficacy of
      a unilateral hemilaminectomy as the surgical approach of choice for excision of
      juxtamedullary spinal neoplasms. MATERIALS AND METHODS: From January 2001 to
      December 2010, 83 patients (male: female ratio: 58: 25, mean age 37.4 years,
      median age 45 years) harboring a juxta-medullary spinal neoplasm were managed at
      our center. The radiological investigations included a contrast-enhanced magnetic
      resonance imaging (MRI) scan, (in the axial, sagittal and coronal planes). A high
      speed drill and an operating microscope assisted in the microsurgical excision of
      these neoplasms. During follow-up, MRI scans were obtained to check for any
      residual tumor. RESULTS: Complete tumor excision was achieved for all patients.
      At a mean follow-up of 17.6 months, the patients had improved to a better
      clinical status. The immediate postoperative complications in the form of
      paraparesis and cerebrospinal fluid leak were seen in 1 patient each,
      respectively; while none of the patients either developed post-operative spinal
      instability or required conversion of the hemilaminectomy to a conventional full
      laminectomy. CONCLUSION: A unilateral hemilaminectomy is recommended as the
      microsurgical approach of choice for juxtamedullary spinal neoplasms.

PMID- 25947991
TI  - History of neurosurgery in Sher-I-Kashmir Institute of Medical Sciences.
AB  - Sher-i-Kashmir Institute of Medical Sciences (SKIMS) is the only tertiary care
      institute in the state of Jammu and Kashmir. The department of neurosurgery was
      established nearly three decades ago and continues to be the leader in providing
      high quality neurosurgical services in the region. The article provides an
      insight into the genesis of the department and its sustained growth over these
      years. It also describes the plans for its future development. 

PMID- 25947992
TI  - Magnetic resonance sequences: Practical neurological applications.

PMID- 25947993
TI  - A summary of some of the recently published, seminal papers in Neuroscience.

PMID- 25947994
TI  - Pituitary cachexia after rabies encephalitis.

PMID- 25947995
TI  - Schwannoma of medial cord of the brachial plexus: An uncommon localisation.

PMID- 25947996
TI  - Anaphylaxis during percutaneous kyphoplasty for an osteoporotic vertebral
      fracture.

PMID- 25947998
TI  - Meningeal melanocytoma of the middle cranial fossa (the Meckel's cave).

PMID- 25947997
TI  - Symptomatic improvement of traumatic dysgeusia from an occipital nerve block.

PMID- 25947999
TI  - Unilateral spatial neglect as a presenting manifestation of nonconvulsive status
      epilepticus.

PMID- 25948000
TI  - Bilateral ptosis after burr hole evacuation of a chronic subdural hematoma.

PMID- 25948001
TI  - Azygous anterior cerebral artery with an anterior cranial fossa base meningioma.

PMID- 25948002
TI  - Transient Kluver-Bucy syndrome from methamphetamine withdrawal.

PMID- 25948003
TI  - Ulnar nerve tuberculoma masquerading as a neurofibroma.

PMID- 25948004
TI  - Large thrombosed anterior communicating artery aneurysm in the sella turcica: A
      review of literature.

PMID- 25948005
TI  - Primary carnitine deficiency presenting as intractable seizures.

PMID- 25948006
TI  - Postoperative arachnoid cyst causing visual deterioration following
      transsphenoidal excision of a pituitary adenoma.

PMID- 25948007
TI  - CD45-negative primary diffuse large B-cell lymphoma of the cerebellum.

PMID- 25948008
TI  - Traumatic atlantoaxial rotatory subluxation with remote cervical spinal cord
      contusion in a child.

PMID- 25948009
TI  - Chronic calcified extradural and subdural hematoma following a
      ventriculoperitoneal shunt placement.

PMID- 25948010
TI  - Spinal gout: A rare cause of paraplegia.

PMID- 25948011
TI  - Rapid resolution of an acute subdural hematoma in Dandy Walker syndrome.

PMID- 25948012
TI  - Need for brain aneurysm treatment registry of India: How effectively are we
      treating intracranial aneurysms in India?

PMID- 25948013
TI  - Approach to diagnosis and management of optic neuropathy due to copper
      deficiency.

PMID- 25948014
TI  - Validity versus reliability.

PMID- 25948015
TI  - Role of ocular ultrasound in idiopathic intra-cranial hypertension.

PMID- 25948016
TI  - An ethical issue at follow-up.

PMID- 25948017
TI  - Professor Subimal Roy (1933-2015): Our teacher in neuropathology.

PMID- 25948018
TI  - Optimal methodology is important for optimal pharmacokinetic studies, therapeutic
      drug monitoring and patient care.

PMID- 25948019
TI  - Ring size in cyclic endomorphin-2 analogs modulates receptor binding affinity and
      selectivity.
AB  - The study reports the solid-phase synthesis and biological evaluation of a series
      of new side chain-to-side chain cyclized opioid peptide analogs of the general
      structure Tyr-[D-Xaa-Phe-Phe-Asp]NH2, where Xaa = Lys (1), Orn (2), Dab (3), or
      Dap (4) (Dab = 2,4-diaminobutyric acid, Dap = 2,3-diaminopropionic acid),
      containing 17- to 14-membered rings. The influence of the ring size on binding to
      the MOP, DOP and KOP opioid receptors was studied. In general, the reduction of
      the size of the macrocyclic ring increased the selectivity for the MOP receptor.
      The cyclopeptide incorporating Xaa = Lys displayed subnanomolar MOP affinity but
      modest selectivity over the KOP receptor, while the analog with the Orn residue
      showed increased affinity and selectivity for MOP. The analog with Dab was a weak
      MOP agonist and did not bind to the other two opioid receptors. Finally, the
      peptide with Xaa = Dap was completely MOP receptor-selective with subnanomolar
      affinity. Interestingly, the deletion of one Phe residue from 1 led to the 14
      membered Tyr-c[D-Lys-Phe-Asp]NH2 (5), a potent and selective MOP receptor ligand.
      The in vitro potencies of the new analogs were determined in a calcium
      mobilization assay performed in Chinese Hamster Ovary (CHO) cells expressing
      human recombinant opioid receptors and chimeric G proteins. A good correlation
      between binding and the functional test results was observed. The influence of
      the ring size, solid support and the N-terminal protecting group on the formation
      of cyclodimers was studied.

PMID- 25948021
TI  - A new approach to elucidating repair reactions of resveratrol.
AB  - The repair by co-antioxidants of the phenoxy radical of resveratrol, the famous
      health-preserving ingredient of red wine, is a key step of radical scavenging
      cascades in nature. To generate that radical, we employed 355 nm photoionization
      as a direct and selective access that reduces the chemical complexity and is
      equally applicable in organized phases; to monitor it, we used its hitherto
      unreported absorption in the red where no other species in our systems interfere.
      With this novel approach, we measured rate constants and H/D kinetic isotope
      effects for the repairs by ascorbate, trolox (a vitamin E analogue) and 4
      aminophenol, and identified the mechanisms as one-step hydrogen abstractions.
      Cysteine and glutathione are unreactive. In micellar solution (SDS), the repair
      by ascorbate is much slower and involves only the hydrophilic phenoxy moieties
      protruding from the micelles. The new experimental strategy also led to a
      reevaluation of extinction coefficients, rate constants and mechanisms. 

PMID- 25948022
TI  - Childhood obesity and environmental pollutants: a dual relationship.
AB  - The rise in obesity rates is an alarming global health concern. Despite obesity
      is mainly due to an unbalanced energy intake and expenditure, several recent
      studies suggest that it could be a consequence of exposure during critical
      developmental windows to environmental chemicals disrupting endocrine functions.
      This suggests that a shift is occurring in the human body pathways used to
      integrate changing nutritional and environmental variables and to maintain
      metabolic balance and body weight. This review highlights the role of pesticides,
      in particular endocrine disrupter ones, on obesity pathogenesis in childhood and
      summarizes the current under-standing of the major environmental influences on
      pediatric obesity. (www.actabiomedica.it). 

PMID- 25948023
TI  - Surgical treatment for functional ischemic mitral regurgitation: current options
      and future trends.
AB  - There is an increasing number of patients with mitral regurgitation secondary to
      dilated cardiomyopathy. Ischemic mitral regurgitation is a common complication of
      left ventricular dysfunction related to chronic coronary artery disease: it is
      present in 10-20% of these patients and is associated with a worse prognosis also
      after coronary revascularization. Currently, coronary artery bypass grafting
      combined with restrictive annuloplasty is the most commonly performed surgical
      procedure, although novel approaches have been used with varying degrees of
      success. The suboptimal results obtained with the commonly used surgical
      approaches require the development of alternative surgical techniques with the
      aim to correct  the causal mechanisms of the disease. In fact the pathophysiology
      of ischemic mitral regurgitation is  multifactorial involving global and regional
      left ventricular remodeling, as well as the dysfunction and distortion of the
      components of the entire mitral valve apparatus. The purpose of this review is to
      present the current surgical techniques available for the treatment of ischemic
      mitral regurgitation and to discuss novel approaches to the repair of this
      complex disease. (www.actabiomedica.it). 

PMID- 25948024
TI  - Niccolo Paganini: the hands of a genius.
AB  - Niccolo Paganini was a man stricken by many diseases and according to Myron
      Schonenfield and Renzo Mantero, he may have also suffered from Marfan Syndrome.
      The following paper is based on actual physical examinations reports made by his
      contemporary physicians, documented in personal letters In addition, the current
      investigation presents a comparison between a post-mortem mold of Paganini's
      right hand and several paintings of the Maestro drawn by Lyser, his personal
      portraitist, and the images of the hand of a well-known musician affected by
      Marfan Syndrome which was treated by the authors. (www.actabiomedica.it). 

PMID- 25948025
TI  - Improving laboratory test ordering can reduce costs in surgical wards.
AB  - Background and Aim Laboratory blood tests for hospitalized patients are often
      overused. Excessive costs and no proof of benefit suggest re-evaluating the
      current approach to laboratory test ordering. The aim of the study is to improve
      the decision-making process of test ordering and to investigate what effect a
      rational, evidence-based use of laboratory test ordering in surgical wards would
      have on costs and healthcare resources. Methods Three-phase experimental
      prospective study carried out at the tertiary referral teaching hospital of
      Parma. Phase 1 (baseline status). The baseline status of laboratory test ordering
      was evaluated by recording the number of biochemical tests requested for patients
      undergoing elective surgery. Laboratory tests were grouped in "recommended" (RT)
      and "non recommended" (nRT) tests on the basis of pertinent literature. Phase 2
      (improvement action): new guidelines were introduced into clinical practice.
      Phase 3 (feedback): Prospective data collection for first and second feedback was
      performed with no advance notice. Results A highly significant reduction in test
      ordering was found on occasion of the phases 2 and 3 of the study. The overall
      number of tests decreased, largely due to a decrease in the use of nRT.
      Conclusions Analysis was justified by the fact that most test requests proved not
      to be supported by clinical evidence. Inappropriate ordering of laboratory tests
      results in an unnecessarily high number of requests, which do not in turn improve
      patient management. Moreover, more appropriate, evidence-based laboratory test
      ordering for patients undergoing elective surgery may produce a significant
      reduction in costs, particularly in high-cost settings. (www.actabiomedica.it). 

PMID- 25948026
TI  - Costs optimization in anaesthesia.
AB  - OBJECTIVES: The aim of this study is to analyze the direct cost of different
      anaesthetic techniques used within the Author's hospital setting and compare with
      costs reported in the literature. METHODS: Mean cost of drugs and devices used in
      our local Department of Anaesthesia was considered in the present study. All
      drugs were supplied by the in-house Pharmacy Service of Parma's General Hospital.
      All calculation have been made using an hypothetical ASA1 patient weighting 70
      kg. The quality of consumption and cost of inhalation anaesthesia with
      sevoflurane or desflurane at different fresh gas flow were analyzed, and the cost
      of total venous anaesthesia (TIVA) using propofol and remifentanil with balanced
      anaesthesia were also analyzed. In addition, direct costs of general, spinal and
      sciatic-femoral nerve block anaesthesia used for common plastic surgery
      procedures were assessed. RESULT: The results of our study show that the cost of
      inhalational anaesthesia decreases using fresh gas flow below 1L, and the use of
      desflurane is more expensive. In our Hospital, the cost of TIVA is more or less
      equivalent to the costs of balanced anaesthesia with sevoflurane in surgical
      procedure lasting more than five hours. The direct cost was lower for the spinal
      anaesthesia compared with general anaesthesia and sciatic- femoral nerve block
      for some surgical procedures. (www.actabiomedica.it).

PMID- 25948027
TI  - Comparison of two different approaches to hypotension following spinal
      anaesthesia for Caesarean delivery: effects on neonatal and maternal wellbeing.
AB  - BACKGROUND: Maternal hypotension during spinal anaesthesia for Caesarean delivery
      is a common event, with potential detrimental consequences. We led a prospective,
      randomized study to compare the effects of two strategies on neonatal and
      maternal wellbeing. METHODS: Parturients scheduled for elective Caesarean section
      in spinal anaesthesia were preoperatively studied with a supine stress test.
      Those with a positive test were enrolled in the study and received a solution of
      0.5% hyperbaric bupivacaine 12.5 mg and 0.02% morphine 200 ug intrathecally.
      Patients received a 37.5 mg/h preventive intravenous (IV) infusion of ephedrine
      (Pharmacologic Group), or a 15 degrees  left lateral tilt (Non-Pharmacologic
      Group). In Pharmacolgic Group hypotension was treated for 20% drops in systolic
      blood pressure; in Non-Pharmacolgic Group only severe hypotension - defined as a
      40% drop in systolic blood pressure - was treated. RESULTS: Thirty-six patients
      were studied. Study groups were statistically similar in terms of demographic
      variables and intraoperative times. No statistical differences were found in
      terms of umbilical arterial blood base excess [-1.4 (-3.7 to -0.3) mEq/l
      Pharmacologic Group vs. -1.7 (-2.7 to -1.0) mEq/l Non-Pharmacologic Group;
      p=0.815] and other umbilical blood gas values. Apgar scores were statistically
      similar between study groups. Treatment for hypotension was required by 13
      (72.2%) patients in Pharmacologic Group and 9 (50%) patients in Non-Pharmacologic
      Group (p=0.171). No differences were found at the analysis of serial changes in
      vital signs. CONCLUSIONS: Both studied strategies guaranteed a comparable safe
      outcome in terms of maternal and neonatal wellbeing. (www.actabiomedica.it).

PMID- 25948028
TI  - Efficacy of a novel food supplement in the relief of the signs and symptoms of
      seasonal allergic rhinitis and in the reduction of the consumption of anti
      allergic drugs.
AB  - BACKGROUND: Seasonal Allergic rhinitis (SAR) is characterized by runny nose,
      congestion, sneezing and sinus pressure. A clinical study was performed to
      demonstrate the efficacy of Lertal(r), an innovative food supplement containing
      Quercetin, Perilla frutescens and Vitamin D3 formu-lated in a double layer "fast
      slow" release tablet form, in the relief of symptoms of seasonal allergic
      rhinitis and in the reduction of consumption of anti-allergic drugs. PATIENTS AND
      METHODS: 23 subjects enrolled in the open clinical study had at least one year
      history of allergic rhinitis and positive skin prick test or RAST to Parietaria
      officinalis pollen. At baseline, the subjects had symptoms of nasal and/or ocular
      seasonal allergic rhinitis. The activity of the food supplement was evaluated
      using the Total Symptoms Score at first (baseline) and second (final) visit,
      after one month of supplementation. The consumption of anti-allergic drugs was
      also evaluated. RESULTS: All subjects enrolled completed the study. The
      comparison of the scores obtained in the two visits (baseline and final) showed a
      highly significant reduction of the overall symptoms: approximately 70% for
      symptom scores and 73% in use of anti-allergic drugs. Sneezing, rhinorrhea, nasal
      obstruction, ocular itching, lacrimation and congestion of the conjunctiva, all
      showed a highly significant reduction. No noteworthy side effect was recorded and
      all patients finished the study with good compliance. CONCLUSIONS: The results
      showed a clear efficacy of the food supplement Lertal(r) in reducing nasal and/or
      eye symptoms. This activity was objectively confirmed by the reduction in the
      consumption of anti-allergic drugs used to relieve symptoms.
      (www.actabiomedica.it).

PMID- 25948029
TI  - The burden of vitamin D deficiency in a mediterranean country without a policy of
      food fortification.
AB  - BACKGROUND: Vitamin D deficiency is a public healthcare issue and its correction
      is increasingly regarded as a cornerstone of preventive medicine. METHODS: We
      designed a retrospective observational study to clearly define the burden of
      total vitamin D (25-hydroxyvitamin D) deficiency in a supposedly healthy
      population of outpatients residing in two regions (Emilia Romagna and Veneto) of
      Northern Italy. RESULTS: 25-hydroxyvitamin D results were available for a total
      number of 5,096 outpatients in the two centers. The median value of 25
      hydroxyvitamin D was 60 nmol/L, and was higher in women than in men (62 nmol/L
      versus 56 nmol/L; p<0.001). The rate of 25-hydroxyvitamin D deficiency was 36%,
      and was marginally but significantly higher in men than in women (40% versus 35%;
      p=0.003). A significant variation in the rate of 25-hydroxyvitamin D deficiency
      was found throughout different age ranges, exhibiting a significant increase in
      the elderly. CONCLUSIONS: The results of this large observational study show that
      the burden of 25-hydroxyvitamin D deficiency in two regions of a Mediterranean
      country without a policy of food fortification is as high as 36%, and this
      evidence represents a background for healthcare preventive measures aimed at
      reducing the prevalence of this condition in the general population.
      (www.actabiomedica.it).

PMID- 25948030
TI  - VAP or poisoning; which one has more effect on patients' outcomes in
      toxicological ICU?
AB  - BACKGROUND: Ventilator-associated pneumonia (VAP) is the main cause of acquired
      infections in ICUs. Every year, millions of people suffer from poisoning by
      various substances. Our aim was to determine the association between VAP
      incidence and different kinds of toxicity among Toxicological ICU (TICU)
      patients.  MATERIALS AND METHODS: Poisoned patients with diagnosis of VAP were
      enrolled to our retrospective study at TICU of Loghman Hakim Hospital. Data was
      collected through the medical records. The statistical analysis was performed
      with SPSS (version 16, Chicago, IL, USA). RESULTS: Among 675 patients with MV >
      48 h, 150 patients had the diagnosis of VAP.  Mean age was 36.6 years. 74.7% were
      males. Intentional poisoning was 70.3%. The incidence of VAP was 22%. The higher
      incidence of VAP was recorded in anti depressants and opioid toxicities. The
      majority of bacterial isolates (81.3%) were multi drug resistance. MRSA accounted
      for 50.7% of VAP cases. Non survivors' hospital length of stay (mean = 18.7days)
      was significantly higher than survivors (12.8). The hospital length of stay in
      VAP patients was highest in the Acinetobacter spp (mean > 20 days). Mortality
      rate of VAP cases was 18.6%. CONCLUSION: No specific association was detected
      between incidence of VAP and different kinds of toxicity, while Anti Depressants
      and opioids had high VAP incidence, in a Quarter of this population. It is
      noticeable that pesticide had the lowest incidence for its short hospitalization.
      In our TICU, MRSA and Acinetobacter spp were the main agents leading to VAP and
      prolonged ICU stay, respectively. (www.actabiomedica.it).

PMID- 25948031
TI  - Complex fractures of the humeral shaft treated with antegrade locked
      intramedullary nail: clinical experience and long-term results.
AB  - BACKGROUND: indications for surgical treatment of complex humeral shaft fractures
      are still controversial. The purpose of this study was to evaluate the outcomes
      of treating humeral shaft fractures using antegrade locked  intramedullary nail,
      compared to the treatment with traditional more aggressive techniques such as
      plate and screws. METHODS: between February 2008 and January 2011 38 patients
      were treated with antegrade locked intramedullary nail for humeral shaft
      fractures, divided according to the AO classification. 28 patients were
      clinically followed: disability, pain and functional recovery were evaluated
      using the Constant score and DASH score and the ROM of the shoulder was checked.
      RESULTS: Bony union was obtained in 27 patients at a mean time of 2.7 months. One
      fracture ended in nonunion, healed after replacing the nail with a longer one.
      Patients achieved satisfactory shoulder function with a mean Constant score of 
      90.57 points and with a mean DASH score of 4.69 points. There were no other
      complications. CONCLUSION: the antegrade locked intramedullary nail represents a
      recommended option for the treatment of humeral shaft fractures, obtaining a
      steady synthesis, a short time of consolidation and a rapid functional recovery.
      (www.actabiomedica.it).

PMID- 25948032
TI  - Coronary CT angiography using iterative reconstruction ?vs. filtered back
      projection: evaluation of image quality.
AB  - OBJECTIVES: To compare image quality of iterative reconstruction algorithm(IRIS)
      vs. standard filtered back projection(FBP) reconstruction in CT Coronary
      Angiography (CTCA). MATERIALS AND METHODS: Thirty-four consecutive patients
      underwent CTCA for suspected or known CAD with Dual-Source CT (DSCT-Flash,
      Siemens). All datasets were reconstructed with 0.75/0.4 and 0.6/0.4 mm slice
      thickness/increment, using three standard FBP kernels (B26-B30-B46) and three
      comparable IRIS algorithms (I26-I30-I46). Vascular attenuation and noise were
      measured. CT vascular attenuation values [HU] were measured in: ascending aorta
      (Ao), right (RCA) and left (LCA) coronary artery, respectively. Signal-to-noise
      (SNR) and contrast-to-noise (CNR) ratio were calculated. A p-value<0.05 was
      considered significant. RESULTS: There was no significant difference between the
      vascular attenuation values measured with FBP (Ao:458HU, RCA:448HU, LAD:444HU)
      and IRIS (Ao:456HU, RCA:446HU, LAD:442HU). Difference in noise was significant
      between FBP (24+/-SD) and IRIS (19+/-SD) (r=0.34;p<0.05). Lowest noise was found
      for IRIS using 0.6 mm (17HU). IRIS provided a SNR and CNR significantly higher
      with increasing kernel sharpness. SNR was 33.3+/-25.1, 77.3+/-51.7, 37.2+/-36.6,
      64.4+/-59.2, while CNR was 25.32+/-19.8, 58.0+/-36.0, 28.6+/-23.5, 47.6+/-47.3
      for 0.75B, 0.75I, 0.6B and 0.6I, respectively. IRIS showed an improvement in SNR
      of 57% and 56% for 0.75 mm and 0.6 mm, respectively, and an improvement in CNR of
      42% and 40% for 0.75 mm and 0.6 mm. CONCLUSIONS: In CTCA, iterative
      reconstructions provide a significant higher image quality compared with the
      conventional FBP reconstructions. (www.actabiomedica.it).

PMID- 25948033
TI  - Detrimental predictive effect of metabolic syndrome on postoperative
      complications in patients who undergoing coronary artery bypass grafting.
AB  - BACKGROUND: The present study came to address the value of metabolic syndrome
      (MetS) in predicting postoperative outcome following coronary artery bypass
      grafting (CABG). METHODS: In a retrospective study, a consecutive series of
      patients including 2010 subjects who underwent isolated CABG were reviewed.
      Baseline information and intraoperative details were collected by reviewing
      hospital-recorded files. The composite outcome of major adverse cardiac and
      cerebrovascular events (postoperative morbidity) was generated from the
      occurrence of myocardial infarction, cardiac arrhythmias, stroke, renal failure,
      and other cardiac-related problems. RESULTS: Overall, 2010 patients who underwent
      isolated CABG were studied that among them 24.7% suffered from MetS. No
      difference was found in the prevalence of postoperative arrhythmias, brain
      stroke, multi-organ failure, and dialysis between the two groups with and without
      MetS. Early morbidity rate was 27.4% in MetS group and 27.8% in non-MetS group
      with no significant discrepancy. Using multivariable logistic regression
      modeling, we showed that MetS status could not predict postoperative morbidity;
      however, advanced age, history of congestive heart failure, higher Canadian
      Cardiovascular Society (CCS) scale, and longer cross-clamp time were main
      indicators of postoperative morbidity.  CONCLUSION: MetS has no detrimental
      predictive effect on early postoperative morbidity in CABG patients.
      (www.actabiomedica.it).

PMID- 25948034
TI  - Validation of a modified model of TNBS-induced colitis in rats. How to induce a
      chemical colitis in rats.
AB  - BACKGROUND: There is no standard practice in the induction of colitis by 2,4,6
      trinitrobenzene sulfonic (TNBS) acid. Usually, the repeated administration of
      TNBS is preferred, because it will result in a local Th1 response that has the
      characteristics of Crohn's disease. MATERIALS AND METHODS: A total of 30 rats
      were randomized into two groups, consisting of a saline control group of ten rats
      and a TNBS groups of 20 rats. After the animals were anesthetized, 0.5 ml of
      either 0.9% saline (controls) or TNBS 50 mg/kg dissolved in 50% ethanol were
      instilled into the colon through a rubber catheter. The experiment was repeated
      weekly for four weeks, then, the rats were killed at day 40, and the distal colon
      removed. RESULTS: At day 40, the bowel wall was basically normal in the control
      group. In the TNBS group, the bowel lumen became narrow with thickened wall, and
      the mucosal surface presented adherent membrane with brown black, linear ulcers,
      proliferous lymphocyte tissue, inflammatory granulomas and submucosal neutrophil
      infiltration. The median score of the severity of the colonic damage was 0 in the
      control group, and 4,75 (range 4-5) in the TNBS group; the mean weight of the
      rats was 180+35 g in the TNBS group, while it was 215+25 in the control group.
      CONCLUSIONS: The presented experiment is a cost-effective and safe method to
      induce Crohn-like colonic damage using a lower dose of TNBS, thus avoiding the
      risk of a massive loss of rats. This model is rather suitable for the assessment
      of the effects of potential therapeutic agents. (www.actabiomedica.it).

PMID- 25948035
TI  - Retroperitoneal cystoadenocarcinoma: a case report with a literature review.
AB  - Primary retroperitoneal mucinous cystoadenocarcinoma (PRMC) is an extremely rare
      clinical entity with about 50 cases described by the literature. Given the rarity
      of this pathology, the sharing of accurate available informations is  important
      to  improve its knowledge. We reported a case of a woman diagnosed with PRMC who
      received different lines of chemotherapy and radiotherapy and we also performed a
      review of the literature on the issue. (www.actabiomedica.it). 

PMID- 25948036
TI  - Successful surgical treatment of a four part fracture dislocations of the
      proximal humerus and coracoid avulsion.
AB  - racture-dislocation of the proximal humerus (usually occurring after violent
      trauma) may be more frequently associated with a poor long-term results because
      the destruction of the hinged periosteum is associated with an high-risk of
      avascular necrosis of the head of the humerus (1, 2). Concomitant coracoid
      fracture with anterior shoulder dislocation in such case is something extremely
      rarely reported (8). Herein, we describe a challenging case of a 44 years old man
      with 4-parts fracture of the right proximal humerus, dislocation of the
      glenohumeral joint associated with coracoid avulsion. Considering the severe
      functional damage on the right shoulder, the patient was immediately treated with
      open reduction internal fixation (ORIF) at the level of the proximal humerus and
      with the concomitant placement of one screw at the level of coracoid avulsion. At
      a 15 months follow up we observed an excellent clinical and radiographic results.
      We take the opportunity of this unusual case for briefly discuss on such clinical
      condition and surgical options. (www.actabiomedica.it). 

PMID- 25948038
TI  - [Not Available].

PMID- 25948037
TI  - The birth and evolution of the Ministry of Health and of the National Health
      Service in Italy.
AB  - Current Ministries of Health (MH) have fundamental commitments in the body of
      modern States and exercise a number of functions that mainly regard the safeguard
      of human and animal health and medical-health planning and management. The many
      and various tasks of third millennium MH range from the surveillance of the
      safety of alimentary products, workplaces and the general environment to the
      organization of health professions and structures, from veterinaryservices to
      scientific research in the health context, from prevention of disorders to care
      and rehabilitation of diseases (1). [...]. 

PMID- 25948039
TI  - The Role of Maternal Knowledge of Child Development in Predicting Risk for Child
      Maltreatment.

PMID- 25948040
TI  - Diabetic Ketoacidosis and Fluid Refractory Hypotension.

PMID- 25948041
TI  - "It Just Consumes Your Life": Quality of Life for Informal Caregivers of Diverse
      Older Adults With Late-Life Disability.
AB  - Little is known about the quality of life (QoL) for informal caregivers of
      disabled older adults aged 65+ with diverse backgrounds. Forty-two caregivers
      were interviewed in English and Cantonese about their caregiving experiences,
      their recollections of QoL over time, and the factors influencing their
      appraisals. Overall, 52% of caregivers experienced a decline in QoL. Factors
      associated with decreased QoL were less time for self, competing financial
      demands, and the physical and emotional impact of the patient's illness. Factors
      associated with no change in QoL were minimal caregiving responsibilities, a
      sense of filial duty, and QoL being consistently poor over time. Factors
      associated with improved QoL were perceived rewards in caregiving, receiving
      institutional help, and increased experience. Chinese caregivers were more likely
      to cite filial duty as their motivator for continued caregiving than were
      Caucasian caregivers. In conclusion, informal caregivers take on a huge burden in
      enabling older adults to age in the community. These caregivers need more support
      in maintaining their QoL. 

PMID- 25948042
TI  - [Asymmetry in digit length in cows with sole ulcer. A post-mortem study of
      slaughter cows].
AB  - OBJECTIVE: In this study, the disparity between the lengths of the lateral and
      medial digit in cows with a Rusterholz sole ulcer compared to non-affected cows
      was investigated. MATERIAL AND METHODS: In total, 100 hind feet were collected
      from slaughtered cows. Twenty-five feet had a pre-ulcerative lesion at the
      typical site, 26 had an ulcer < 1 cm2 and 24 had an ulcer > 1.5 cm2. Twenty-five
      normal feet were used as controls. The lengths of the metatarsal condyles and
      phalanges (Ph) were measured on plantarodorsal radiographs and three different
      overall lengths of the digits were generated. The software program SPSS was used
      for analysis. RESULTS: The mean lengths of Ph1 and Ph2 and the three mean overall
      lengths of the lateral digit were greater than those of the medial digit while
      the length of Ph3 was longer on the medial digit. With one exception, the
      comparison of overall length 2 of the pre-ulcerative lesion with the control
      group, the within-feet differences of the ulcer groups were not significantly
      different from the difference of the controls. CONCLUSION AND CLINICAL RELEVANCE:
      These results corroborate the length asymmetry of the bovine digits but further
      studies are needed to evaluate the effect of the asymmetry of the digits on the
      development of sole ulcers.

PMID- 25948043
TI  - Recombinant pigment epithelium-derived factor PEDF binds vascular endothelial
      growth factor receptors 1 and 2.
AB  - Angiogenesis, or the formation of new blood vessels, is stimulated by angiogenic
      factors such as vascular endothelial growth factor (VEGF). Pigment epithelium
      derived factor (PEDF) is a potent inhibitor of angiogenesis. To explore the
      mechanism by which PEDF acts, recombinant PEDF was expressed with a 6x-His tag
      (for purification) and a green fluorescent protein (GFP) tag. The PEDF fusion
      protein was confirmed to be active in inhibition of endothelial cell
      proliferation and migration. Direct binding of PEDF to both vascular endothelial
      growth factor receptor-1 (VEGFR-1) and VEGFR-2 was demonstrated in an in vitro
      assay similar to an enzyme-linked immunosorbent assay (ELISA). PEDF was shown by
      immune-confocal microscopy to be localized within treated endothelial cells. When
      VEGF-stimulated endothelial cells were incubated with PEDF the VEGF receptors
      showed intracellular localization. These data suggest that the interaction
      between PEDF and VEGFR-1 or VEGFR-2 may be a possible mechanism for inhibiting
      angiogenesis. PEDF may be binding to the VEGF receptors to promote their
      internalization and/or degradation to limit VEGF responses in treated cells. 

PMID- 25948045
TI  - Progress testing 2.0: clinical skills meets necessary science.
AB  - INTRODUCTION: Progress testing has been widely used in medical schools to test
      scientific knowledge but has not been reported for assessing clinical skills.
      DEVELOPMENT: We designed a novel progress examination that included assessments
      of both clinical performance and underlying basic and social science knowledge.
      This Progress Clinical Skills Examination (PCSE) was given to 21 early medical
      students at the beginning and end of a 6-week pilot test of a new medical school
      curriculum. IMPLEMENTATION: This examination was feasible for early students,
      easy to map to curricular objectives, and easy to grade using a combination of
      assessment strategies. FUTURE DIRECTIONS: Use of a PCSE is feasible for early
      medical students. As medical schools integrate clinical experience with
      underlying knowledge, this type of examination holds promise. Further data are
      needed to validate this examination as an accurate measure of clinical
      performance and knowledge.

PMID- 25948044
TI  - Use of cell lines and primary cultures to explore the capacity of rainbow trout
      to be a host for frog virus 3 (FV3).
AB  - The capacity of rainbow trout, Oncorhynchus mykiss, to be a host for frog virus 3
      (FV3) was evaluated at the cellular level. Cell cultures from this species were
      tested for their ability to express FV3 major capsid protein (MCP) gene, to
      develop cytopathic effect (CPE), and to produce FV3. After FV3 addition, MCP
      transcripts were detected in six of six cell lines and in primary macrophage
      cultures. CPE developed in all cell culture systems, except primary lymphocytes.
      For the macrophage cell line, RTS11, and primary macrophages, cell death was by
      apoptosis because DNA laddering and Annexin staining were detected. By contrast,
      markers of apoptosis did not accompany CPE in three epithelial cell lines from
      the gill (RTgill-W1), intestine (RTgut-GC), and liver (RTL-W1) and in two
      fibroblast cell lines from gonads (RTG-2) and skin (RTHDF). Therefore, FV3 was
      able to enter and begin replicating in several cell types. Yet, FV3 was produced
      in only two cell lines, RTG-2 and RTL-W1, and only modestly. Overall, these
      results suggest that if tissue accessibility were possible, FV3 would have the
      capacity to induce injury, but the ability to replicate would be limited, likely
      making rainbow trout a poor host for FV3.

PMID- 25948046
TI  - Pediatric ischemic stroke from an apoplectic prolactinoma.
AB  - INTRODUCTION: Pediatric pituitary neoplasms and associated pituitary apoplexy are
      uncommon. There are few reports in pediatric patients of pituitary apoplexy
      causing focal arterial compression or diffuse vasospasm resulting in cerebral
      infarction, and the acute, focal neurological deficits associated with stroke
      differ from the typical presentation of an apoplectic pituitary tumor. We report
      the first case of a teenage female with an apoplectic macroprolactinoma
      presenting with stuttering cerebral infarction secondary to compression of the
      internal carotid artery (ICA). CASE: A 14-year-old female was transferred from an
      outside facility after presenting with right hand paresthesias and word-finding
      difficulty that eventually progressed to include right upper extremity weakness
      and mental status changes. Computed tomography (CT) and magnetic resonance
      imaging (MRI) revealed an apoplectic macroprolactinemia and diffusion-weighted
      imaging showed acute stroke in the left anterior and middle cerebral artery
      distributions. Evaluation of the cerebral vasculature with MRA showed focal
      compression of the left supraclinoid ICA. Despite prompt surgical decompression,
      the patient developed right lower extremity weakness in addition to her other
      deficits though her deficits improved after inpatient rehabilitation.
      CONCLUSIONS: In the pediatric population, there is only one other case of
      pituitary apoplexy presenting with stroke, which was secondary to vasospasm. We
      present the first case of pituitary apoplexy presenting with stroke secondary to
      ICA compression. Though rare, it is important to consider that pituitary apoplexy
      may present with non-classical symptoms such as ischemic stroke even in pediatric
      patients.

PMID- 25948047
TI  - Engineering microaerobic metabolism of E. coli for 1,2-propanediol production.
AB  - Establishment of novel metabolic pathways for biosynthesis of chemicals, fuels
      and pharmaceuticals has been demonstrated in Escherichia coli due to its ease of
      genetic manipulation and adaptability to varying oxygen levels. E. coli growing
      under microaerobic condition is known to exhibit features of both aerobic and
      anaerobic metabolism. In this work, we attempt to engineer this metabolism for
      production of 1,2-propanediol. We first redirect the carbon flux by disrupting
      carbon-competing pathways to increase the production of 1,2-propanediol
      microaerobically from 0.25 to 0.85 g/L. We then disrupt the first committed step
      of E. coli's ubiquinone biosynthesis pathway (ubiC) to prevent the oxidation of
      NADH in microaerobic conditions. Coupling this strategy with carbon flux
      redirection leads to enhanced production of 1,2-propanediol at 1.2 g/L. This work
      demonstrates the production of non-native reduced chemicals in E. coli by
      engineering its microaerobic metabolism. 

PMID- 25948048
TI  - Stabilization of single species Synechocystis biofilms by cultivation under
      segmented flow.
AB  - The application of segmented flow on a Synechocystis sp. PCC 6803 biofilm
      prevented excessive biomass formation and clogging by fundamentally changing the
      structure of the microbial community. It was possible to continuously operate a
      capillary microreactor for 5 weeks, before the experiment was actively
      terminated. The biofilm developed up to a thickness of 70-120 um. Surprisingly,
      the biofilm stopped growing at this thickness and stayed constant without any
      detachment events occurring afterwards. The substrates CO2 and light were
      supplied in a counter-current fashion. Confocal microscopy revealed a throughout
      photosynthetically active biofilm, indicated by the red fluorescence of photo
      pigments. This control concept and biofilm reaction setup may enable continuous
      light driven synthesis of value added compounds in future.

PMID- 25948049
TI  - Engineering Escherichia coli for high-level production of propionate.
AB  - Mounting environmental concerns associated with the use of petroleum-based
      chemical manufacturing practices has generated significant interest in the
      development of biological alternatives for the production of propionate. However,
      biological platforms for propionate production have been limited to strict
      anaerobes, such as Propionibacteria and select Clostridia. In this work, we
      demonstrated high-level heterologous production of propionate under microaerobic
      conditions in engineered Escherichia coli. Activation of the native Sleeping
      beauty mutase (Sbm) operon not only transformed E. coli to be propionogenic
      (i.e., propionate-producing) but also introduced an intracellular "flux
      competition" between the traditional C2-fermentative pathway and the novel C3
      fermentative pathway. Dissimilation of the major carbon source of glycerol was
      identified to critically affect such "flux competition" and, therefore,
      propionate synthesis. As a result, the propionogenic E. coli was further
      engineered by inactivation or overexpression of various genes involved in the
      glycerol dissimilation pathways and their individual genetic effects on
      propionate production were investigated. Generally, knocking out genes involved
      in glycerol dissimilation (except glpA) can minimize levels of solventogenesis
      and shift more dissimilated carbon flux toward the C3-fermentative pathway. For
      optimal propionate production with high C3:C2-fermentative product ratios,
      glycerol dissimilation should be channeled through the respiratory pathway and,
      upon suppressed solventogenesis with minimal production of highly reduced
      alcohols, the alternative NADH-consuming route associated with propionate
      synthesis can be critical for more flexible redox balancing. With the
      implementation of various biochemical and genetic strategies, high propionate
      titers of more than 11 g/L with high yields up to 0.4 g-propionate/g-glycerol
      (accounting for ~50 % of dissimilated glycerol) were achieved, demonstrating the
      potential for industrial application. To our knowledge, this represents the most
      effective engineered microbial system for propionate production with titers and
      yields comparable to those achieved by anaerobic batch cultivation of various
      native propionate-producing strains of Propionibacteria. 

PMID- 25948050
TI  - Electron flux and microbial community in microbial fuel cells (open-circuit and
      closed-circuit modes) and fermentation.
AB  - A closed-circuit microbial fuel cell (C-MFC) was operated to investigate the
      electron flux under fed-batch mode, and the results were compared to those of
      open-circuit MFC (O-MFC) and a fermentation reactor (F-reactor). The current was
      the largest electron sink (52.7% of influent SCOD) in C-MFC, whereas biomass and
      methane gas were the most significant electron sinks in O-MFC and F-reactor.
      Interestingly, some of the unknown sink may have accumulated in the electrode of
      O-MFC. Principal component analysis based on gradient gel electrophoresis
      profiles showed that the microbial communities were significantly affected by the
      growth conditions and the presence of electrode, regardless of the circuit
      connection. Therefore, the electrode and circuit mode might help to control the
      amount of biomass and enhance the MFC performance.

PMID- 25948052
TI  - Age-associated modifications of intestinal permeability and innate immunity in
      human small intestine.
AB  - The physical and immunological properties of the human intestinal epithelial
      barrier in aging are largely unknown. Ileal biopsies from young (7-12 years),
      adult (20-40 years) and aging (67-77 years) individuals not showing symptoms of
      gastrointestinal (GI) pathologies were used to assess levels of inflammatory
      cytokines, barrier integrity and cytokine production in response to microbial
      challenges. Increased expression of interleukin (IL)-6, but not interferon
      (IFN)gamma, tumour necrosis factor (TNF)-alpha and IL-1beta was observed during
      aging; further analysis showed that cluster of differentiation (CD)11c(+)
      dendritic cells (DCs) are one of the major sources of IL-6 in the aging gut and
      expressed higher levels of CD40. Up-regulated production of IL-6 was accompanied
      by increased expression of claudin-2 leading to reduced transepithelial electric
      resistance (TEER); TEER could be restored in in vitro and ex vivo cultures by
      neutralizing anti-IL-6 antibody. In contrast, expression of zonula occludens-1
      (ZO-1), occludin and junctional-adhesion molecule-A1 did not vary with age and
      overall permeability to macromolecules was not affected. Finally, cytokine
      production in response to different microbial stimuli was assessed in a polarized
      in vitro organ culture (IVOC). IL-8 production in response to flagellin declined
      progressively with age although the expression and distribution of toll-like
      receptor (TLR)-5 on intestinal epithelial cells (IECs) remained unchanged. Also,
      flagellin-induced production of IL-6 was less pronounced in aging individuals. In
      contrast, TNF-alpha production in response to probiotics (VSL#3) did not decline
      with age; however, in our experimental model probiotics did not down-regulate the
      production of IL-6 and expression of claudin-2. These data suggested that aging
      affects properties of the intestinal barrier likely to impact on age-associated
      disturbances, both locally and systemically. 

PMID- 25948053
TI  - Equine herpesvirus type 1 tegument protein VP22 is not essential for
      pathogenicity in a hamster model, but is required for efficient viral growth in
      cultured cells.
AB  - VP22 is a major tegument protein of Equine herpesvirus type 1 (EHV-1) that is a
      conserved protein among alphaherpesviruses. However, the roles of VP22 differ
      among each virus, and the roles of EHV-1 VP22 are still unclear. Here, we
      constructed an EHV-1 VP22 deletion mutant and a revertant virus to clarify the
      role of VP22. We found that EHV-1 VP22 was required for efficient viral growth in
      cultured cells, but not for virulence in a hamster model. 

PMID- 25948054
TI  - Circulating insulin-like growth factor I in juvenile chum salmon: relationship
      with growth rate and changes during downstream and coastal migration in
      northeastern Hokkaido, Japan.
AB  - Chum salmon (Oncorhynchus keta) migrate to the ocean in their first spring, and
      growth during early marine life is critical for survival. We examined the
      validity of circulating IGF-I and muscle RNA/DNA ratio as indices of growth rate
      using individually tagged juvenile chum salmon fed or fasted for 10 days. Serum
      IGF-I level was highly, positively correlated with individual growth rate. Muscle
      RNA/DNA ratio also showed a positive correlation, but its relation was not as
      high as that of IGF-I. We next measured these physiological parameters in chum
      salmon juveniles caught at river, estuary, port and nearshore of the northeastern
      Hokkaido, Japan, from May to June in 2013 and 2014, respectively. In both years,
      there was a trend that serum IGF-I levels were high in nearshore fish and low in
      river/estuarine fish in June. In contrast, muscle RNA/DNA ratio showed no clear
      temporal and spatial patterns. The present study shows that circulating IGF-I can
      be used as a growth index in juvenile chum salmon. Monitoring growth status using
      serum IGF-I suggests that growth of juvenile chum salmon in the survey area was
      activated when they left the coast. 

PMID- 25948056
TI  - Rhodium-catalyzed enantioselective silylation of arene C-H bonds:
      desymmetrization of diarylmethanols.
AB  - We report a Rh-catalyzed, enantioselective silylation of arene C-H bonds directed
      by a (hydrido)silyl group. (Hydrido)silyl ethers that are formed in situ by
      hydrosilylation of benzophenone or its derivatives undergo asymmetric C-H
      silylation in high yield with excellent enantioselectivity in the presence of
      [Rh(cod)Cl]2 and a chiral bisphosphine ligand. The stereoselectivity of this
      process also allows enantioenriched diarylmethanols to react with site
      selectivity at one aryl group over the other. Enantioenriched benzoxasiloles from
      the silylation process undergo a range of transformations to form C-C, C-O, C-I,
      or C-Br bonds. 

PMID- 25948055
TI  - Physiological response of alligator gar juveniles (Atractosteus spatula) exposed
      to sub-lethal doses of pollutants.
AB  - Alligator gar populations have declined because of overfishing, habitat loss and
      pollution. Over time, the exposure to different pollutants have affected these
      fishes as a consequence of their high trophic level, bottom-dwelling habits and
      long life span. In order to evaluate the physiological effects of pollutants on
      alligator gar, juveniles (6, 12 and 24 months) were exposed to sub-lethal doses
      of diazinon, beta-naphthoflavone (BNF) and 17 beta-estradiol (E2) by
      intraperitoneal injection. After 2 days of exposure, liver samples were taken to
      determine the activities of acetylcholinesterase, butyrylcholinesterase and
      carboxylesterase; alkaline and acid phosphatases (ALP and ACP); ethoxyresorufin o
      deethylase (EROD); glutathione s-transferase (GST); superoxide dismutase (SOD),
      and vitellogenin (VTG) concentration. Two additional bioassays consisting on the
      exposure of compounds through water or food were performed and after 4 and 28
      days, respectively, biomarkers were determined. All esterases were inhibited in
      organisms exposed to diazinon as well as in 6-months gar exposed to E2 and BNF.
      In contrast, ALP activity increased in gar exposed to diazinon and E2, while ACP
      activity did not show any variations. No EROD activity was registered after
      exposure to the different pollutants, despite being one of the most sensitive and
      common detoxification biomarkers used for fishes. GST activity reduction was
      detected when gar were exposed to E2 and BNF, while SOD activity increased after
      exposure to diazinon and E2. Finally, VTG levels were higher in animals exposed
      to E2 compared to other treatments. Overall, these results suggest that alligator
      gar juveniles have a low biotransformation metabolism and show that they are
      especially sensitive to those pollutants affecting the nervous system.

PMID- 25948057
TI  - Motivation modulates the effect of approach on implicit preferences.
AB  - With three studies, we investigated whether motivational states can modulate the
      formation of implicit preferences. In Study 1, participants played a video game
      in which they repeatedly approached one of two similar beverages, while
      disregarding the other. A subsequent implicit preference for the target beverage
      emerged, which increased with participants' thirst. In Study 2, participants
      approached one brand of potato chips while avoiding the other: Conceptually
      replicating the moderation observed in Study 1, the implicit preference for the
      approached brand increased with the number of hours from last food intake. In
      Study 3, we experimentally manipulated hunger, and the moderation effect emerged
      again, with hungry participants displaying a higher implicit preference for the
      approached brand, as compared to satiated participants. In the three studies, the
      moderation effect was not paralleled in explicit preferences although the latter
      were affected by the preference inducing manipulation. Theoretical implications
      and open questions are discussed. 

PMID- 25948058
TI  - Workplace violence towards workers in the emergency departments of Palestinian
      hospitals: a cross-sectional study.
AB  - BACKGROUND: Workplace violence (WPV) in hospital emergency departments (EDs) is a
      common problem. The objective of this study was to assess the characteristics
      (level and type), associated risk factors, causes, and consequences of WPV
      against workers in Palestinian EDs. METHODS: A cross-sectional study was
      conducted in 14 out of the available 39 EDs in Palestine: 8 from the West Bank
      and 6 from the Gaza Strip. Data were collected using a self-administered
      questionnaire between July-September 2013. Multivariate logistic regression
      models were used to examine risk factors associated with exposure to WPV.
      RESULTS: A total of 444 participants (response rate 74.5%): 161 (32.0%) nurses,
      142 (32%) physicians, and 141 (31.7%) administrative personnel. The majority
      (76.1%) experienced a type of WPV in the past 12 months: 35.6% exposed to
      physical and 71.2% to non-physical assaults (69.8% verbal abuses, 48.4% threats,
      and 8.6% sexual harassments). Perpetrators of physical and non-physical violence
      were mainly patients' families/visitors (85.4% and 79.5%, respectively). Waiting
      time, lack of prevention measures, and unmet expectations of patients and their
      families are the main reasons for WPV. The multivariate regression analysis
      showed that younger personnel (OR = 2.29 CI 95% 1.309-4.036), clinicians (nurses
      and physicians) (OR = 1.65 CI 95% 0.979-2.797) comparing with administrative, and
      less experienced ED personnel (OR = 2.39 CI 95% 1.141-5.006) are significantly at
      higher risk of exposure to WPV (P < 0.05). Low level (40%) of violence reporting
      is evident, largely attributed to not enough actions being taken and fear of
      consequences. Violence has been shown to have considerable consequences for
      workers' well-being, patient care, and job retention. CONCLUSIONS: Violence
      against workers in Palestinian EDs is highly common. The effects of violence are
      considerable. Multiple factors cause violence; however, EDs' internal-system
      related factors are the most amenable to change. Attention should be given to
      strengthening violence prevention policy and measures and improving incident
      reporting system.

PMID- 25948060
TI  - Winston A et al (Clin Infect Dis 2015; 60:1026-32).

PMID- 25948059
TI  - Community-based directly observed therapy (DOT) versus clinic DOT for
      tuberculosis: a systematic review and meta-analysis of comparative effectiveness.
AB  - BACKGROUND: Directly observed therapy (DOT), as recommended by the World Health
      Organization, is used in many countries to deliver tuberculosis (TB) treatment.
      The effectiveness of community-based (CB DOT) versus clinic DOT has not been
      adequately assessed to date. We compared TB treatment outcomes of CB DOT
      (delivered by community health workers or community volunteers), with those
      achieved through conventional clinic DOT. METHODS: We performed a systematic
      review and meta-analysis of studies before 9 July 2014 comparing treatment
      outcomes of CB DOT and clinic DOT. The primary outcome was treatment success; the
      secondary outcome was loss to follow-up. RESULTS: Eight studies were included
      comparing CB DOT to clinic DOT, one a randomised controlled trial. CB DOT
      outperformed clinic DOT treatment success (pooled odds ratio (OR) of 1.54, 95%
      confidence interval (CI) 1.01 - 2.36, p = 0.046, I(2) heterogeneity 84%). No
      statistically significant difference was found between the two DOT modalities for
      loss to follow-up (pooled OR 0.86, 95% CI 0.48 to 1.55, p = 0.62, I(2) 83%).
      CONCLUSIONS: Based on this systematic review, CB DOT has a higher treatment
      success compared to clinic DOT. However, as only one study was a randomised
      controlled trial, the findings have to be interpreted with caution.

PMID- 25948061
TI  - Acute gastrointestinal graft-vs-host disease is associated with increased enteric
      bacterial bloodstream infection density in pediatric allogeneic hematopoietic
      cell transplant recipients.
AB  - BACKGROUND: Bacterial septicemia remains the leading cause of morbidity and
      mortality following allogeneic hematopoietic cell transplantation (AlloHCT).
      While murine studies have found acute gastrointestinal graft-vs-host disease (aG
      GVHD) to be associated with increased incidence of enteric bacterial bloodstream
      infections (EB-BSI), this association has not been studied in humans. We
      hypothesized that in patients who developed aG-GVHD, the EB-BSI density after
      onset of aG-GVHD would be higher than before onset and higher than in patients
      without acute GVHD (aGVHD). METHODS: We retrospectively reviewed data collected
      on 264 pediatric AlloHCT recipients with malignant and nonmalignant disease. We
      calculated and compared EB-BSI densities in the following 3 subgroups: patients
      without aGVHD and patients with aG-GVHD, both before and after onset of aG-GVHD.
      We also examined the effect of aG-GVHD onset on the first episode of EB-BSI using
      Cox proportional hazards models. RESULTS: The overall incidence of aG-GVHD was
      28.8% (n = 76). Analyses done both at 120 and 180 days post-AlloHCT showed that
      the EB-BSI density increased after aG-GVHD onset (0.95 infections/person-year
      before aG-GVHD vs 2.7 infections/person-year after aG-GVHD at day 120 [P = .006];
      0.95 infections/person-year before aG-GVHD vs 2.26 infections/person-year after
      aG-GVHD at day 180 [P = .033]). On multivariate analysis, the onset of aG-GVHD
      had a positive hazard ratio of 1.47 (P = .077) on time to first EB-BSI.
      CONCLUSIONS: Our results support the theory that aG-GVHD predisposes pediatric
      AlloHCT recipients to EB-BSI. Prophylactic agents such as probiotics should be
      studied prospectively in patients with aG-GVHD.

PMID- 25948062
TI  - Editorial commentary: the gut microbiota strikes again.

PMID- 25948063
TI  - Genotypic and Spatial Analysis of Mycobacterium tuberculosis Transmission in a
      High-Incidence Urban Setting.
AB  - BACKGROUND: Genotyping Mycobacterium tuberculosis isolates allows study of
      dynamics of tuberculosis transmission, while geoprocessing allows spatial
      analysis of clinical and epidemiological data. Here, genotyping data and spatial
      analysis were combined to characterize tuberculosis transmission in Vitoria,
      Brazil, to identify distinct neighborhoods and risk factors associated with
      recent tuberculosis transmission. METHODS: From 2003 to 2007, 503 isolates were
      genotyped by IS6110 restriction fragment length polymorphism (RFLP) and
      spoligotyping. The analysis included kernel density estimation, K-function
      analysis, and a t test distance analysis. Mycobacterium tuberculosis isolates
      belonging to identical RFLP patterns (clusters) were considered to represent
      recent tuberculosis infection (cases). RESULTS: Of 503 genotyped isolates, 242
      (48%) were categorized into 70 distinct clusters belonging to 12 RFLP families.
      The proportion of recent transmission was 34.2%. Kernel density maps indicated 3
      areas of intense concentration of cases. K-function analysis of the largest RFLP
      clusters and families showed they co-localized in space. The distance analysis
      confirmed these results and demonstrated that unique strain patterns (controls)
      randomly distributed in space. A logit model identified young age, positive smear
      test, and lower Index of Quality of Urban Municipality as risk factors for recent
      transmission. The predicted probabilities for each neighborhood were mapped and
      identified neighborhoods with high risk for recent transmission. CONCLUSIONS:
      Spatial and genotypic clustering of M. tuberculosis isolates revealed ongoing
      active transmission of tuberculosis caused by a small subset of strains in
      specific neighborhoods of the city. Such information provides an opportunity to
      target tuberculosis transmission control, such as through rigorous and more
      focused contact investigation programs.

PMID- 25948065
TI  - Photo- and electro-luminescence of four cuprous complexes with sterically
      demanding and hole transmitting diimine ligands.
AB  - Four new cuprous complexes (1-4) containing bisphosphine and triazolylpyridine
      donors have been prepared in order to examine the effects of the methyl group and
      the carbazole appendage on photo- and electro-luminescence (PL and EL)
      properties. Because of their additional steric hindrance from the methyl
      substituent group at a 6-pyridine ring, complexes 3 and 4, compared with the
      methyl group free compounds 1 and 2, expectedly exhibit largely spectral blue
      shift and higher intensity both in PL and EL. Meanwhile, the carbazole appendage
      of complexes 2 and 4 does not significantly alter their PL performance in
      comparison with 1 and 3, respectively, but have a modest increase in their EL
      efficiency in multilayer organic light-emitting diodes (OLEDs). Moreover, the
      OLED with 4 as the light emitting material has the highest current efficiency
      (CEmax) of 27.2 cd A(-1) and the maximum external quantum efficiency (EQEmax) of
      8.7%.

PMID- 25948066
TI  - Follicular Unit Extraction Hair Transplantation with Micromotor: Eight Years
      Experience.
AB  - OBJECTIVE: Follicular unit extraction (FUE) has been performed for over a decade.
      Our experience in the patients who underwent hair transplantation using only the
      FUE method was included in this study. METHODS: A total of 1000 patients had hair
      transplantation using the FUE method between 2005 and 2014 in our clinic.
      RESULTS: Manual punch was used in 32 and micromotor was used in 968 patients for
      graft harvesting. During the time that manual punch was used for graft
      harvesting, 1000-2000 grafts were transplanted in one session in 6-8 h. Following
      micromotor use, the average graft count was increased to 2500 and the operation
      time remained unchanged. Graft take was difficult in 11.1 %, easy in 52.2 %, and
      very easy in 36.7 % of our patients. CONCLUSIONS: The main purpose of hair
      transplantation is to restore the hair loss. During the process, obtaining a
      natural appearance and adequate hair intensity is important. In the FUE method,
      grafts can be taken without changing their natural structure, there is no need
      for magnification, and the grafts can be transplanted directly without using any
      other processes. Because there is no suture in the FUE method, patients do not
      experience these incision site problems and scar formation. The FUE method
      enables us to achieve a natural appearance with less morbidity.

PMID- 25948064
TI  - Doxycycline Leads to Sterility and Enhanced Killing of Female Onchocerca volvulus
      Worms in an Area With Persistent Microfilaridermia After Repeated Ivermectin
      Treatment: A Randomized, Placebo-Controlled, Double-Blind Trial.
AB  - BACKGROUND: Ivermectin (IVM) has been the drug of choice for the treatment of
      onchocerciasis. However, there have been reports of persistent microfilaridermia
      in individuals from an endemic area in Ghana after many rounds of IVM, raising
      concerns of suboptimal response or even the emergence of drug resistance. Because
      it is considered risky to continue relying only on IVM to combat this phenomenon,
      we assessed the effect of targeting the Onchocerca volvulus Wolbachia
      endosymbionts with doxycycline for these individuals with suboptimal response.
      METHODS: One hundred sixty-seven patients, most of them with multiple rounds of
      IVM, were recruited in areas with IVM suboptimal response and treated with 100
      mg/day doxycycline for 6 weeks. Three and 12 months after doxycycline treatment,
      patients took part in standard IVM treatment. RESULTS: At 20 months after
      treatment, 80% of living female worms from the placebo group were Wolbachia
      positive, whereas only 5.1% in the doxycycline-treated group contained bacteria.
      Consistent with interruption of embryogenesis, none of the nodules removed from
      doxycycline-treated patients contained microfilariae, and 97% of those patients
      were without microfilaridermia, in contrast to placebo patients who remained at
      pretreatment levels (P < .001). Moreover, a significantly enhanced number of dead
      worms were observed after doxycycline. CONCLUSIONS: Targeting the Wolbachia in O.
      volvulus is effective in clearing microfilariae in the skin of onchocerciasis
      patients with persistent microfilaridermia and in enhanced killing of adult worms
      after repeated standard IVM treatment. Strategies can now be developed that
      include doxycycline to control onchocerciasis in areas where infections persist
      despite the frequent use of IVM. CLINICAL TRIALS REGISTRATION: ISRCTN 66649839.

PMID- 25948067
TI  - A Quantitative Analysis of Lip Aesthetics: The Influence of Gender and Aging.
AB  - INTRODUCTION: The quantitative analysis of sexual dimorphism of facial structures
      may valuably support reconstructive and feminization surgery, thanks to the
      estimation of metrical thresholds useful for distinguishing male and female
      traits. This study aims at verifying the metrical characteristics of female and
      male lips, to provide indications for aesthetic surgery. METHODS: Thirty healthy
      Caucasian volunteers (20 men and 20 women) were divided into two groups according
      to age: 21-34 years and 45-65 years. Arches and the cutaneous (external) and
      mucosal (internal) labial surfaces were reproduced by stone models, and digitised
      using a computerised electromechanical instrument. Area, volume and thickness
      were measured separately for the upper and lower lips, and compared between sexes
      and ages by Student's t test, and multinomial logistic regression. RESULTS: All
      lip measurements were larger in males than in females; upper lip thickness best
      divided males from females, adopting a 9.5-mm threshold (percentage of correct
      diagnosis: 85 %). Young subjects always showed higher measurements than old
      subjects; lower lip thickness provided the highest percentage of correct age
      diagnosis (85 %, adopting a 13.8-mm threshold). CONCLUSION: This study provides
      novel thresholds that may contribute to the assessment of adequate reconstruction
      of lips in aesthetic surgery. LEVEL OF EVIDENCE III: 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- 25948068
TI  - Comparison of Various Rhinoplasty Techniques and Long-Term Results.
AB  - BACKGROUND: Various techniques are used in rhinoplasty. These techniques can be
      classified under transcolumellar approaches and endonasal procedures. Open
      rhinoplasty without transcolumellar incision (ORWTI) procedure can be described
      as a combination of these two techniques. METHODS: In this study, we present
      patients who underwent nasal surgery utilizing one of these three techniques
      between 1999 and 2013 and discuss some modifications to the techniques. RESULTS:
      Of a total of 1526 patients, 1131 were operated on with open rhinoplasty with
      transcolumellar incision, 219 were operated on with ORWTI, and 176 were operated
      on using the endonasal approach. With an average follow-up period of
      approximately 4 years, 4 % of the patients required revision. The patient
      satisfaction rate was more than 90 % for all of these techniques. CONCLUSIONS:
      The endonasal approach is an appropriate choice for select patients due to the
      lower chance of complications and a shorter procedure time. With open rhinoplasty
      with the transcolumellar incision technique, the type of surgery can be more
      easily controlled, however, extended nasal tip edema and columellar scar are some
      of the disadvantages of this method. ORWTI allows a patient to avoid these
      disadvantages and provides a more controlled procedure, similar to the open
      method.

PMID- 25948069
TI  - SEW2871 Alleviates the Severity of Caerulein-Induced Acute Pancreatitis in Mice.
AB  - Sphingosine-1-phosphate type-1 receptor (S1P1) agonists have the potential to
      inhibit the egress of lymphocytes, and have been demonstrated to provide
      protective effects on some acute inflammatory diseases. However, the value of
      S1P1 agonists on acute pancreatitis (AP) remains unclear. The aim of this study
      was to explore the effect of SEW2871, a S1P1-selective agonist, on caerulein
      induced AP in mice. AP was induced by giving eight intraperitoneal injections of
      caerulein (50 ug/kg/h) at hourly intervals. SEW2871 was administered by gavage,
      at a dose of 20 mg/kg, at 0 h and 12 h after the first intraperitoneal injection
      of caerulein. The mice were sacrificed at 24 h. Severity of AP, serum amylase and
      lipase activity, levels of serum cytokines, pancreatic myeloperoxidase (MPO)
      activity, CD45+CD4+ T lymphocytes in blood, CD4+ T cell infiltration in the
      pancreas, and proinflammatory cytokine production were assessed. Furthermore, the
      expression of signal transducer and activator of transcription (STAT) 3 and
      phospho-STAT3 (p-STAT3) in the pancreas was also evaluated. The results revealed
      that the administration of SEW2871 ameliorated the severity of AP, by a reduction
      of serum pancreatic enzyme activity and levels of cytokines, decreased pancreatic
      MPO activity, depletion of CD4+CD45+ T lymphocytes in the blood and a reduction
      of CD4+ T cell infiltration in the pancreas. Furthermore, the expression of
      proinflammatory cytokines mRNA and p-STAT3 were also suppressed by SEW2871
      treatment. These results suggest that SEW2871 treatment attenuates the severity
      of caerulein-induced AP in mice, which may provide a new therapeutic approach for
      AP therapy. 

PMID- 25948070
TI  - Biomarkers Related to Carotid Intima-Media Thickness and Plaques in Long-Term
      Survivors of Ischemic Stroke.
AB  - Lifestyle risk factors, inflammation and genetics play a role in the development
      of atherosclerosis. We therefore studied Fc gamma receptor (FcgammaR)
      polymorphisms, interleukin (IL)-10 polymorphisms and other biomarkers related to
      carotid intima-media thickness (cIMT) in patients with ischemic stroke at a young
      age. Patients were evaluated 12 years after stroke occurrence. Patients (n = 232)
      49 years of age or younger with an index stroke between 1988 and 1997 were
      retrospectively selected. Blood samples were taken at a first follow-up 6 years
      after the stroke. At a second follow-up, additional arterial events were
      registered for 140 patients, new blood samples were taken, and measurements of
      cIMT and blood pressure (BP) were performed. Unadjusted logistic regression
      analysis showed that cIMT >=1 mm was associated with age, male gender, additional
      arterial events, BP, cholesterol, sedimentation rate, haemoglobin, triglycerides,
      creatinine, glycolysed haemoglobin (HbA1c) and FcgammaRIIIB-NaII/NaII. Adjusted
      backward stepwise logistic regression showed significance for age (odds ratio
      (OR) 1.13, 95% confidence interval (CI) 1.04 to1.23, p = 0.003), male gender (OR
      4.07, 95% CI 1.15 to 14.5, p = 0.030), HbA1c (OR 6.65, 95% CI 1.21 to 36.5, p =
      0.029) and FcgammaRIIIB-NaII/NaII (OR 3.94, 95% CI 1.08 to 14.3, p = 0.037). In
      this long-term follow-up study of patients with ischemic stroke at a young age,
      FcgammaRIIIB-NaII/NaII was identified as a possible contributing factor for cIMT
      >=1 mm together with known risk factors, such as age, male gender, systolic BP,
      additional arterial events and HbA1c.

PMID- 25948071
TI  - Concepts of pathogenesis in psoriatic arthritis: genotype determines clinical
      phenotype.
AB  - This review focuses on the genetic features of psoriatic arthritis (PsA) and
      their relationship to phenotypic heterogeneity in the disease, and addresses
      three questions: what do the recent studies on human leukocyte antigen (HLA) tell
      us about the genetic relationship between cutaneous psoriasis (PsO) and PsA -
      that is, is PsO a unitary phenotype; is PsA a genetically heterogeneous or
      homogeneous entity; and do the genetic factors implicated in determining
      susceptibility to PsA predict clinical phenotype? We first discuss the results
      from comparing the HLA typing of two PsO cohorts: one cohort providing the
      dermatologic perspective, consisting of patients with PsO without evidence of
      arthritic disease; and the second cohort providing the rheumatologic perspective,
      consisting of patients with PsA. We show that these two cohorts differ
      considerably in their predominant HLA alleles, indicating the heterogeneity of
      the overall PsO phenotype. Moreover, the genotype of patients in the PsA cohort
      was shown to be heterogeneous with significant elevations in the frequency of
      haplotypes containing HLA-B*08, HLA-C*06:02, HLA-B*27, HLA-B*38 and HLA-B*39.
      Because different genetic susceptibility genes imply different disease
      mechanisms, and possibly different clinical courses and therapeutic responses, we
      then review the evidence for a phenotypic difference among patients with PsA who
      have inherited different HLA alleles. We provide evidence that different alleles
      and, more importantly, different haplotypes implicated in determining PsA
      susceptibility are associated with different phenotypic characteristics that
      appear to be subphenotypes. The implication of these findings for the overall
      pathophysiologic mechanisms involved in PsA is discussed with specific reference
      to their bearing on the discussion of whether PsA is conceptualised as an
      autoimmune process or one that is based on entheseal responses. 

PMID- 25948073
TI  - Detraining in pregnancy and/or lactation modulates neuropeptidergic hypothalamic
      systems in offspring mice.
AB  - Manipulations in metabolic parameters during pregnancy/lactation can impact the
      development of short- and long-term energy control mechanisms, which are mainly
      modulated by neural and hormonal inputs to the hypothalamus. Thus, we tested how
      mice training and detraining during pregnancy and lactation affect hypothalamus
      gene expression and change biometric and metabolic profiles of the offspring.
      Three-month-old female Swiss mice were submitted to an 8-week exercise program
      (swimming 5 times/week, 1 h/day). Following this physical exercise protocol,
      these conditioned animals and the control group were submitted to matting. After
      pregnancy verification, the animals were distributed into four groups: training
      during pregnancy and lactation (T); detraining after pregnancy confirmation (DP);
      detraining during lactation (DL); and control (CT), without interventions. After
      weaning, the offspring of the four groups were derived into these as follows: TO,
      DPO, DLO, and CTO, respectively. The body weight was lower in conditioned females
      compared to control at weeks 4-8 of the exercise regimen. No statistical
      difference in dam's body weight was observed during pregnancy. Related to
      offspring, at post-natal day 90, the animals were euthanized and DPO and DLO
      showed decrease in Npy and Cart expression in hypothalamus, and DLO also had
      increased Lep gene expression in white adipose tissue. Additionally, DPO showed
      increase in plasma triglycerides levels, total liver weight, and decrease in
      brown adipose tissue compared to CTO. Together, these results support that
      detraining during critical periods of development leads to altered gene
      expression in hypothalamic neuropeptidergic systems.

PMID- 25948072
TI  - The relationship between long-term proton pump inhibitor therapy and skeletal
      frailty.
AB  - Proton pump inhibitors (PPIs) are a commonly prescribed class of medications.
      Their use has been associated with an increased rate of fractures, most notably
      hip fractures. However, there does not seem to be a clear association between PPI
      use and bone mineral density measurements, assessed by dual X-ray absorptiometry.
      The mechanism by which PPI use increases the risk of fractures remains unclear.
      This review will summarize the current evidence on this topic.

PMID- 25948074
TI  - Associations between a common variant near the MC4R gene and serum triglyceride
      levels in an obese pediatric cohort.
AB  - Polymorphisms near the MC4R gene may be related to an increased risk for obesity,
      but studies of variations in this gene and its relation to cardiometabolic
      profiles and food intake are scarce and controversial. The aim of this study is
      to evaluate the influence of the variants rs12970134 and rs17782313 near the MC4R
      gene in food intake, binge eating (BE) behavior, anthropometric parameters, body
      composition, metabolic profile, and cardiometabolic risk factors in obese
      children and adolescents. This is a cross-sectional study that included obese
      children and adolescents. We evaluated anthropometric, metabolic parameters and
      cardiometabolic risk factors, including hypertension, impaired fasting glucose,
      hypertriglyceridemia, and low HDL-cholesterol. BE was assessed through the BE
      scale, and a 24-h recall was used to evaluate total caloric intake and percentage
      of macronutrients and types of dietary fat. The MC4R variants rs12970134 and
      rs17782313 were genotyped using TaqMan assay. To assess the magnitude of risk, a
      logistic regression adjusted for Z-BMI, age, and gender was performed, adopting
      the significance level of 0.05. The study included 518 subjects (52.1 % girls,
      12.7 +/- 2.7 years old, Z-BMI = 3.24 +/- 0.57). Carriers of the variant
      rs17782313 exhibit increased triglyceride levels (108 +/- 48 vs. 119 +/- 54, p =
      0.034) and an increased risk of hypertriglyceridemia (OR 1.985, 95 % CI 1.288
      3.057, p = 0.002). There was no association of the SNP rs12970134 with clinical,
      metabolic, or nutritional parameters. The variant rs12970134 and rs17782313 did
      not influence food intake or the presence of BE. The variant rs17782313 is
      associated with an increased risk of hypertriglyceridemia in obese children and
      adolescents.

PMID- 25948075
TI  - Predictive value of intratumoral heterogeneity of F-18 FDG uptake for
      characterization of thyroid nodules according to Bethesda categories of fine
      needle aspiration biopsy results.
AB  - The current study was aimed to investigate the clinical value of intratumoral
      heterogeneity of F-18 FDG uptake for characterization of thyroid nodule (TN) with
      inconclusive fine-needle aspiration biopsy (FNAB) results. The current study
      enrolled 200 patients who showed F-18 FDG incidentaloma and were performed FNAB.
      The intratumoral heterogeneity of F-18 FDG uptake was represented as the
      heterogeneity factor (HF), defined as the derivative (dV/dT) of a volume
      threshold function for a primary tumor. The diagnostic and predictive values of
      HF and F-18 FDG PET/CT parameters were evaluated for characterization of
      inconclusive FNAB results. Among F-18 FDG PET/CT parameters, SUVmax, MTV, and TLG
      of malignant group were statistically higher than those of Bethesda category of
      suspicious malignant group. However, HF values were not statistically different
      between the groups of Bethesda categories (Kruskal-Wallis statistics, 9.924; p =
      0.0774). In ROC analysis, when HF > 2.751 was used as cut-off value, the
      sensitivity and specificity for prediction of malignant TN were 100 % (95 % CI
      69.2-100 %) and 60 % (95 % CI 42.1-76.1 %), respectively. The AUC was 0.826 (95 %
      CI 0.684-0.922) and standard error was 0.0648 (p < 0.0001). In conclusion, the
      intratumoral heterogeneity of F-18 FDG uptake represented by HF could be a
      predictor for characterization of TN with inconclusive FNAB results. Additional
      large population-based prospective studies are needed to validate the diagnostic
      utility of HF of F-18 FDG PET/CT.

PMID- 25948077
TI  - A dilemma regarding the optimal administration of nimodipine in the subarachnoid
      hemorrhage.

PMID- 25948076
TI  - Acute subdural hematoma caused by a ruptured cavernous internal carotid artery
      giant aneurysm following abducens nerve palsy: case report and review of the
      literature.
AB  - The authors report a 61-year-old female patient with a giant cavernous aneurysm
      in the right internal carotid artery (ICA) leading to acute subdural hematoma
      (ASDH) 7 days after the occurrence of abducens nerve palsy. She underwent ICA
      occlusion associated with high-flow bypass. In all five reported patients with a
      cavernous ICA aneurysm causing ASDH, the size of the aneurysm was giant and
      cranial nerve signs preceded the rupture. When a patient with a symptomatic
      cavernous ICA giant aneurysm experiences sudden-onset headache and/or
      consciousness disturbance, rupture of the aneurysm should be differentiated, even
      though a cavernous ICA aneurysm rarely causes ASDH.

PMID- 25948078
TI  - Identification of cranial nerves near large vestibular schwannomas using
      superselective diffusion tensor tractography: experience with 23 cases.
AB  - BACKGROUND: The preservation of the facial nerve (FN) and acoustic function in
      large vestibular schwannoma (VS) surgery is challenging because of nerve course
      uncertainties and morphological deviations. Preoperative diffusion tensor
      tractography (DTT) has been proposed to predict the FN location. This study was
      conducted to evaluate the effectiveness of this technique for identifying the FN,
      cochlear nerve (CN) and trigeminal nerve (TN) in large VSs. METHODS: The study
      included 23 consecutive patients with VS of Hannover classification T3b to T4b
      from November 2013 through May 2014. Diffusion tensor images and anatomical
      images were acquired. The DTT images of the cranial nerves were extracted before
      surgery for each patient to determine the relationships of these nerves with the
      tumor. The results were then validated during the tumorectomy. RESULTS: In 21
      (91.30%) patients, the location of the FN on the DTT images agreed with the
      intraoperative findings, including in 2 patients in whom the FN passed through
      the interface between the parenchyma and the cystic changes and in 3 patients
      with a membranoid FN. The CN or fibers of unclear function were observed on DTT
      images in four patients with functional hearing. One penetrating fiber of unknown
      function was effectively constructed. The TN was accurately detected on the DTT
      images for all patients. CONCLUSIONS: DTT effectively revealed the location of
      the FN, including cases in which the FN was membranoid or passed through the
      interface between an area exhibiting cystic changes and the tumor nodule. Fibers
      aside from the FN and the TN were revealed by DTT in patients who retained
      functional hearing. Penetrating fibers were also found using DTT. This technique
      can be useful during VS resection.

PMID- 25948079
TI  - Superficial subarachnoid cerebrospinal fluid space expansion after surgical
      drainage of chronic subdural hematoma.
AB  - BACKGROUND: The present study examined the computed tomography (CT) findings
      after surgery and overnight drainage for chronic subdural hematoma (CSDH) to
      clear the significance of inner superficial subarachnoid CSF space and outer
      subdural hematoma cavity between the brain surface and the inner skull. METHODS:
      A total of 73 sides in 60 patients were evaluated. Head CT was performed on the
      day after surgery and overnight drainage (1st CT), within 3 weeks of surgery (2nd
      CT), and more than 3 weeks after surgery (3rd CT). Subdural and subarachnoid
      spaces were identified to focus on density of fluid, shape of air collection, and
      location of silicone drainage tube, etc. Cases with subdural space larger than
      the subarachnoid CSF space were classified as Group SD between the brain and the
      skull. Cases with subarachnoid CSF space larger than the subdural space were
      classified as Group SA. Cases with extremely thin (<3 mm) spaces between the
      brain and the skull were classified as Group NS. RESULTS: Group SA, SD, and NS
      accounted for 31.9, 55.6 and 12.5% of cases on the 1st CT. No statistical
      differences were found between Groups SA, SD, and NS in any clinical factors,
      including recurrence. Group SA were found significantly more on 1st CT than on
      2nd and 3rd CT. CONCLUSIONS: Subarachnoid CSF space sometimes expands between the
      brain and skull on CT after surgical overnight drainage. Expansion of the
      arachnoid space may be a passive phenomenon induced by overnight drainage and
      delayed re-expansion of the brain parenchyma.

PMID- 25948080
TI  - The suboccipital midline approach to foramen magnum meningiomas: safety and
      efficacy in a series of 23 consecutive patients over a 5-year period.

PMID- 25948082
TI  - Synthesis and testing of ZnO nanoparticles for photo-initiation: experimental
      observation of two different non-migration initiators for bulk polymerization.
AB  - The migration and transport of polymerization initiators are problematic for
      commercially used polymerization procedures. For example, UV printing of
      packaging generates products with potentially harmful components that come in
      contact with food. Enlarging the size of the initiator is the only way to prevent
      contamination, e.g., by gas phase transport. In this manuscript, the synthesis
      and advanced and full analyses of novel nanoparticle-based types of non
      migration, fragmenting and non-fragmenting photo-initiators will be presented in
      detail. This study introduces non-fragmenting/"Norrish type II" and
      fragmenting/"Norrish type I" ZnO nanoparticle-based initiators and compares them
      with two commercial products, a "Norrish type I" initiator and a "Norrish type
      II" initiator. Therefore, inter alia, the recently developed analysis involves
      examining the solidification by UV-vis and the double bond content by Raman.
      Irradiation is performed using absolute and spectrally calibrated xenon flash
      lights. A novel procedure for absolute and spectral calibration of such light
      sources is also presented. The non-optimized "Norrish type II" particle-based
      initiator is already many times faster than benzophenone, which is a molecular
      initiator of the same non-fragmenting type. This experimentally observed
      difference in reactive particle-based systems without co-initiators is
      unexpected. Co-initiators are normally an additional molecular species, which
      leads to migration problems. The discovery of significant initiation potential
      resulting in a very well-dispersed organic-inorganic hybrid material suggests a
      new field of research opportunities at the interface of physical chemistry,
      polymer chemistry and engineering science, with enormous value for human health. 

PMID- 25948081
TI  - Modelling the potential of focal screening and treatment as elimination strategy
      for Plasmodium falciparum malaria in the Peruvian Amazon Region.
AB  - BACKGROUND: Focal screening and treatment (FSAT) of malaria infections has
      recently been introduced in Peru to overcome the inherent limitations of passive
      case detection (PCD) and further decrease the malaria burden. Here, we used a
      relatively straightforward mathematical model to assess the potential of FSAT as
      elimination strategy for Plasmodium falciparum malaria in the Peruvian Amazon
      Region. METHODS: A baseline model was developed to simulate a scenario with
      seasonal malaria transmission and the effect of PCD and treatment of symptomatic
      infections on the P. falciparum malaria transmission in a low endemic area of the
      Peruvian Amazon. The model was then adjusted to simulate intervention scenarios
      for predicting the long term additional impact of FSAT on P. falciparum malaria
      prevalence and incidence. Model parameterization was done using data from a
      cohort study in a rural Amazonian community as well as published transmission
      parameters from previous studies in similar areas. The effect of FSAT timing and
      frequency, using either microscopy or a supposed field PCR, was assessed on both
      predicted incidence and prevalence rates. RESULTS: The intervention model
      indicated that the addition of FSAT to PCD significantly reduced the predicted P.
      falciparum incidence and prevalence. The strongest reduction was observed when
      three consecutive FSAT were implemented at the beginning of the low transmission
      season, and if malaria diagnosis was done with PCR. Repeated interventions for
      consecutive years (10 years with microscopy or 5 years with PCR), would allow
      reaching near to zero incidence and prevalence rates. CONCLUSIONS: The addition
      of FSAT interventions to PCD may enable to reach P. falciparum elimination levels
      in low endemic areas of the Amazon Region, yet the progression rates to those
      levels may vary substantially according to the operational criteria used for the
      intervention.

PMID- 25948084
TI  - The Effect of Natural LCAT Mutations on the Biogenesis of HDL.
AB  - We have investigated how the natural LCAT[T147I] and LCAT[P274S] mutations affect
      the pathway of biogenesis of HDL. Gene transfer of WT LCAT in LCAT(-/-) mice
      increased 11.8-fold the plasma cholesterol, whereas the LCAT[T147I] and
      LCAT[P274S] mutants caused a 5.2- and 2.9-fold increase, respectively. The
      LCAT[P274S] and the WT LCAT caused a monophasic distribution of cholesterol in
      the HDL region, whereas the LCAT[T147I] caused a biphasic distribution of
      cholesterol in the LDL and HDL region. Fractionation of plasma showed that the
      expression of WT LCAT increased plasma apoE and apoA-IV levels and shifted the
      distribution of apoA-I to lower densities. The LCAT[T147I] and LCAT[P274S]
      mutants restored partially apoA-I in the HDL3 fraction and LCAT[T147I] increased
      apoE in the VLD/IDL/LDL fractions. The in vivo functionality of LCAT was further
      assessed based on is its ability to correct the aberrant HDL phenotype that was
      caused by the apoA-I[L159R]FIN mutation. Co-infection of apoA-I(-/-) mice with
      this apoA-I mutant and either of the two mutant LCAT forms restored only
      partially the HDL biogenesis defect that was caused by the apoA-I[L159R]FIN and
      generated a distinct aberrant HDL phenotype. 

PMID- 25948083
TI  - Infusion of donor lymphocytes expressing the herpes simplex virus thymidine
      kinase suicide gene for recurrent hematologic malignancies after allogeneic
      hematopoietic stem cell transplantation.
AB  - The infusion of donor lymphocytes expressing the herpes simplex virus thymidine
      kinase suicide gene (TK-cells) is a promising strategy for the treatment of
      hematologic malignancies relapsing after allogeneic hematopoietic stem cell
      transplantation. Here we report the results of a phase I clinical trial designed
      to examine the feasibility, safety, and efficacy of donor lymphocyte infusion
      (DLI) of TK-cells. Three patients (two with malignant lymphomas, one with acute
      myeloid leukemia) were enrolled in the trial and received a single DLI of 1 *
      10(7) or 5 * 10(7) TK-cells/kg. No local or systemic toxicity related to the gene
      transfer procedure was observed. Two patients achieved stable disease. No patient
      had severe graft-versus-host disease requiring systemic steroid and/or
      ganciclovir administration. TK-cells were detected in the peripheral blood of all
      three patients by PCR, but did not persist longer than 28 days. Analysis of
      cytotoxic T lymphocyte activity detected no immune response against TK-cells by
      the recipient's own T cells. Flow cytometric analysis showed low proliferative
      activity and cytotoxic function of TK-cells. In conclusion, DLI of TK-cells was
      safely performed in all three patients. Our analysis suggests the probable cause
      of rapid disappearance of TK-cells to be insufficient in vivo expansion of TK
      cells in these patients.

PMID- 25948086
TI  - Erratum to: The effectiveness of targeting never or rarely screened women in a
      national cervical cancer screening program for underserved women.

PMID- 25948085
TI  - Identification of deep intronic variants in 15 haemophilia A patients by next
      generation sequencing of the whole factor VIII gene.
AB  - Current screening methods for factor VIII gene (F8) mutations can reveal the
      causative alteration in the vast majority of haemophilia A patients. Yet,
      standard diagnostic methods fail in about 2% of cases. This study aimed at
      analysing the entire intronic sequences of the F8 gene in 15 haemophilia A
      patients by next generation sequencing. All patients had a mild to moderate
      phenotype and no mutation in the coding sequence and splice sites of the F8 gene
      could be diagnosed so far. Next generation sequencing data revealed 23 deep
      intronic candidate variants in several F8 introns, including six recurrent
      variants and three variants that have been described before. One patient
      additionally showed a deletion of 9.2 kb in intron 1, mediated by Alu-type
      repeats. Several bioinformatic tools were used to score the variants in
      comparison to known pathogenic F8 mutations in order to predict their
      deleteriousness. Pedigree analyses showed a correct segregation pattern for three
      of the presumptive mutations. In each of the 15 patients analysed, at least one
      deep intronic variant in the F8 gene was identified and predicted to alter F8
      mRNA splicing. Reduced F8 mRNA levels and/or stability would be well compatible
      with the patients' mild to moderate haemophilia A phenotypes. The next generation
      sequencing approach used proved an efficient method to screen the complete F8
      gene and could be applied as a one-stop sequencing method for molecular
      diagnostics of haemophilia A.

PMID- 25948087
TI  - A multifinger microtriode with carbon nanotubes field emission cathode operating
      at GHz frequency.
AB  - Vacuum microelectronic devices play an important role in the field of micro- and
      nano-electronics and they have been strongly developed in recent decades. Vacuum
      microelectronics are mainly based on the field emission effect and the employment
      of electrons in vacuum in a device with dimensions from tenths to hundredths of a
      micrometer. In this work, we present the development of a carbon-nanotube-based
      multifinger microtriode operating from 0.5 to 2 GHz. In this frequency range, a
      minimum RF signal gain of 5 dB is achieved. Such a device represents an optimized
      alternative to the standard Spindt-type microtriode. The advantage of such
      multifinger architecture consists in the possibility to reduce the cathode-grid
      capacitance by reducing the overlap between the two electrodes using a parallel
      patterning. This approach allows increasing the cut-off frequency of the devices
      with respect to the Spindt-type triode. We realized a prototype of the
      multifinger triode and the field emission properties have been characterized. The
      frequency behavior has been measured, demonstrating the possibility to amplify RF
      signal. 

PMID- 25948088
TI  - Embedded ceria nanoparticles in gel improve electrophoretic separation: a
      preliminary demonstration.
AB  - Slab gel electrophoresis is still the gold standard method for the separation of
      biomolecules such as proteins and DNA with advantages such as simplicity,
      affordability, and high throughput, but it suffers from inadequate separation
      speed and resolution. Single capillary gel electrophoresis, on the other hand,
      offers faster separation time and improved resolution at the expense of higher
      cost and loss of high throughput capability. The high surface to volume ratio of
      the capillary causes improved heat dissipation leading to a reduced Joule heating
      and a higher resolution. Here, for the first time, we show the use of dispersed
      ceria nanoparticles (NPs) to improve the resolution and speed of protein
      separation in slab gel electrophoresis. We measured the rheological parameters of
      separation medium in order to find a meaningful relationship between viscosity
      changes, Joule heating, and band broadening. The results showed that ceria NPs
      decrease the viscosity of polyacrylamide gel. By loading 0.03% (w/v) ceria NPs
      into polyacrylamide gel at 25  degrees C, the viscosity decreased 22% and the
      thermal conductivity increased to 81%, which resulted in 35% reduction in Joule
      heating and 47% increase in resolution. This work is a cross disciplinary of
      theoretical physical chemistry for thermal conductivity and rheological
      measurements of PA and ceria suspensions and application in slab gel
      electrophoresis. We report here, for the first time, that embedded NPs in PA gel
      could potentially interface high throughput capability of slab gel
      electrophoresis with high separation speed of single capillary electrophoresis. 

PMID- 25948090
TI  - Body fat in children and adolescents participating in organized sports:
      Descriptive epidemiological study of 6048 Latvian athletes.
AB  - BACKGROUND: Pressure among young athletes to meet body composition goals may lead
      to poor nutrition and affect growth. AIMS: To examine the proportion of body fat
      (%BF), measured by bioimpedance analysis, among Latvian children and adolescents
      participating in organized sports. METHODS: Our study had a nationally
      representative sample of 6048 young athletes, aged 10-17 years. Their %BF was
      measured using a multifrequency, 8-pole, bioelectrical impedance leg-to-hand
      analyzer. RESULTS: About 19.2% (CI 14.4-20.0) of boys and 15.1% (CI 14.0-16.3) of
      girls had a %BF value below the recommended levels. The %BF in young female
      athletes participating in aesthetic sports was lower than among their peers
      participating in other sports. Young male athletes participating in aesthetic
      sports had lower %BF levels at 10 and 12 years of age, compared with participants
      in weight-class sports; and lower levels of %BF from age 10-14 years, compared
      with participants in non-weight-sensitive sports. CONCLUSIONS: Almost every fifth
      child and adolescent participating in organized sports displayed critically low
      body fat levels. Body fat needs to be assessed regularly in young athletes, to
      prevent negative consequences on health.

PMID- 25948091
TI  - Regional inequalities in pre-pregnancy overweight and obesity in Sweden, 1992,
      2000, and 2010.
AB  - AIMS: To investigate regional differences and time trends in women's overweight
      and obesity in Sweden. METHODS: Using data from the Swedish Medical Birth
      Register (women aged ?18 years, first pregnancy only) and the Total Population
      Register accessed through the Umea SIMSAM Lab, age-standardized prevalence of pre
      pregnancy overweight/obesity (BMI ? 25 kg/m(2)) and obesity (BMI ? 30 kg/m(2))
      were estimated by county for the years 1992, 2000, and 2010. Maps were created
      using ArcMap v10.2.2 to display regional variations over time and logistic
      regression analyses were used to assess if the observed trends were significant.
      RESULTS: The prevalence of pre-pregnancy overweight/obesity and obesity increased
      significantly in all Swedish counties between 1992, and 2010. In 2010,
      Sodermanland and Gotland exhibited the highest age-standardized
      overweight/obesity (39.7%) and obesity (15.1%) prevalence, respectively. The
      sharpest increases between 1992 and 2010 were observed in Vasterbotten for
      overweight/obesity (75% increase) and in Gotland for obesity (233% increase).
      Across the years, Stockholm had the lowest prevalence of overweight/obesity
      (26.3% in 2010) and obesity (7.3% in 2010) and one of the least steep increases
      in prevalence of both between 1992 and 2010. CONCLUSIONS: Substantial regional
      differences in pre-pregnancy overweight and obesity prevalence are apparent in
      Sweden. Further research should elucidate the mechanisms causing these
      differences.

PMID- 25948089
TI  - Functional significance of the sex chromosomes during spermatogenesis.
AB  - Mammalian sex chromosomes arose from an ordinary pair of autosomes. Over hundreds
      of millions of years, they have evolved into highly divergent X and Y chromosomes
      and have become increasingly specialized for male reproduction. Both sex
      chromosomes have acquired and amplified testis-specific genes, suggestive of
      roles in spermatogenesis. To understand how the sex chromosome genes participate
      in the regulation of spermatogenesis, we review genes, including single-copy,
      multi-copy, and ampliconic genes, whose spermatogenic functions have been
      demonstrated in mouse genetic studies. Sex chromosomes are subject to chromosome
      wide transcriptional silencing in meiotic and postmeiotic stages of
      spermatogenesis. We also discuss particular sex-linked genes that escape
      postmeiotic silencing and their evolutionary implications. The unique gene
      contents and genomic structures of the sex chromosomes reflect their strategies
      to express genes at various stages of spermatogenesis and reveal the driving
      forces that shape their evolution.Free Chinese abstract: A Chinese translation of
      this abstract is freely available at http://www.reproduction
      online.org/content/149/6/R265/suppl/DC1.Free Japanese abstract: A Japanese
      translation of this abstract is freely available at http://www.reproduction
      online.org/content/149/6/R265/suppl/DC2. 

PMID- 25948092
TI  - Thermodynamically Stable Pickering Emulsion Configured with Carbon-Nanotube
      Bridged Nanosheet-Shaped Layered Double Hydroxide for Selective Oxidation of
      Benzyl Alcohol.
AB  - A simple strategy to configure a high thermodynamically stable Pickering emulsion
      with 2D sheet-shaped layered double hydroxide (LDH) coupled carbon nanotube (CNT)
      nanohybrid (LDH-CNT) is reported. With the benefit of a unique 2D sheet-shaped
      structure of the LDH, the as-made LDH-CNTs with amphiphilicity as solid
      emulsifiers have a good capability for assembling and stabilizing at the water
      oil interface, and a superior thermostability emulsion is delivered, indicative
      of an increased catalytic performance for selective oxidation of benzyl alcohol
      to benzaldehyde. Such a unique and excellent thermodynamic stability
      characteristic makes high reaction interfacial areas well-kept during the
      reaction process, yielding high catalytic performance. The present strategy
      provides a simple method for configuration and design of solid nanoparticle
      emulsifiers with high thermodynamic stability, which will make such a material be
      of great potential in many important applications such as catalysis and
      emulsifiers. 

PMID- 25948093
TI  - Endovascular coil detachment causing EMG artefact in BIS: a mechanistic
      exploration.
AB  - Deployment of endovascular coils used in interventional neuroradiology commonly
      involves electrolytic detachment of the coil from the pusher catheter. This
      report describes a case of artefactual increase in electromyography (EMG) values
      of bispectral index (BIS) monitor during coil detachment. An explanation of this
      event is provided connecting mechanism of coil detachment and derivation of EMG
      values in a BIS monitor. While rising EMG values are thought to arise from
      frontalis contraction, they may as well be an unrecognized electrical artefact,
      especially in context of undistorted electroencephalography waveform.

PMID- 25948094
TI  - Utilization of contraceptives by persons living with HIV in Eastern Uganda: a
      cross sectional study.
AB  - BACKGROUND: In Uganda, there has been an increase in use of contraceptives by 6%
      from 2006 to 2011 among married women. During the same period HIV prevalence had
      gone up by 0.9%. Lack of use of contraceptives especially among persons living
      with HIV may escalate the spread of the virus. The purpose of the study was to
      determine the rate of contraceptive use and associated factors among persons
      receiving HIV care and treatment in Eastern Uganda. METHODS: A cross-sectional
      study was conducted in 4 public hospitals of Mbale, Kapchorwa, Atutur and Pallisa
      in Eastern Uganda. In total, 300 respondents comprising of women aged (15-49) and
      men (15-54) years were interviewed using interviewer administered questionnaires.
      However, data from 298 respondents were analyzed using multinomial logistic
      regression at alpha = 0.05 in STATA statistical software (Version 10). RESULTS:
      Approximately 62% (185/298) of persons living with HIV had used contraceptives
      within the three months preceding the study. Among the significant predictors,
      higher proportions of female respondents aged 36-49 years used injectables and
      male aged 50-54 years used condoms (p = 0.030 and p = 0.034, respectively).
      Furthermore, higher proportions of respondents with primary, secondary and
      tertiary education levels were more likely to use condoms (p = 0.004, p = 0.000
      and p = 0.005, respectively) compared with those who never went to school.
      Besides, condoms were being used by Protestants (p = 0.000) compared to Catholics
      and Muslims. Also, more female respondents (p = 0.000) used condoms with their
      partners compared with the male counterparts. The main barrier to contraceptive
      use among non-users was desire for more children. CONCLUSION: More efforts are
      needed to sensitize and provide contraceptives targeting the illiterate clients,
      youth, men and believers from different religious sects to increase utilization.

PMID- 25948095
TI  - Extreme (13)C depletion of carbonates formed during oxidation of biogenic methane
      in fractured granite.
AB  - Precipitation of exceptionally 13C-depleted authigenic carbonate is a result of,
      and thus a tracer for, sulphate-dependent anaerobic methane oxidation,
      particularly in marine sediments. Although these carbonates typically are less
      depleted in 13C than in the source methane, because of incorporation of C also
      from other sources, they are far more depleted in 13C (delta13C as light as 
      690/00 V-PDB) than in carbonates formed where no methane is involved. Here we
      show that oxidation of biogenic methane in carbon-poor deep groundwater in
      fractured granitoid rocks has resulted in fracture-wall precipitation of the most
      extremely 13C-depleted carbonates ever reported, delta13C down to -1250/00 V-PDB.
      A microbial consortium of sulphate reducers and methane oxidizers has been
      involved, as revealed by biomarker signatures in the carbonates and S-isotope
      compositions of co-genetic sulphide. Methane formed at shallow depths has been
      oxidized at several hundred metres depth at the transition to a deep-seated
      sulphate-rich saline water. This process is so far an unrecognized terrestrial
      sink of methane. 

PMID- 25948099
TI  - Analysing half-lives for pesticide dissipation in plants.
AB  - Overall dissipation of pesticides from plants is frequently measured, but the
      contribution of individual loss processes is largely unknown. We use a pesticide
      fate model for the quantification of dissipation by processes other than
      degradation. The model was parameterised using field studies. Scenarios were
      established for Copenhagen/Denmark and Shanghai/PR China, and calibrated with
      measured results. The simulated dissipation rates of 42 pesticides were then
      compared with measured overall dissipation from field studies using tomato and
      wheat. The difference between measured overall dissipation and calculated
      dissipation by non-degradative processes should ideally be contributable to
      degradation in plants. In 11% of the cases, calculated dissipation was above the
      measured dissipation. For the remaining cases, the non-explained dissipation
      ranged from 30% to 83%, depending on crop type, plant part and scenario.
      Accordingly, degradation is the most relevant dissipation process for these 42
      pesticides, followed by growth dilution. Volatilisation was less relevant, which
      can be explained by the design of plant protection agents. Uptake of active
      compound from soil into plants leads to a negative dissipation process (i.e. a
      gain) that is difficult to quantify because it depends largely on interception,
      precipitation and plant stage. This process is particularly relevant for soluble
      compounds. 

PMID- 25948100
TI  - Higher frequency of regulatory T cells in granulocyte colony-stimulating factor
      (G-CSF)-primed bone marrow grafts compared with G-CSF-primed peripheral blood
      grafts.
AB  - BACKGROUND: Regulatory T cells (Treg) in allografts are important for the
      prevention of graft-versus-host disease (GVHD) post-transplantation. The aim of
      this study was to compare the contents of Tregs and effector T cells in
      granulocyte colony-stimulating factor (G-CSF)-primed bone marrow grafts (G-BM)
      and peripheral blood grafts (G-PB). METHOD: G-BM and G-PB were obtained from 20
      allogeneic donors. T-cell subgroups, including conventional T cells and different
      types of Treg cells, as well as the percentage of Ki67 expression on
      CD4(+)CD25(high)Foxp3(+) Treg cells, were analyzed using flow cytometry. The
      levels of interferon-gamma (IFN-gamma) and interleukin-17 (IL-17) secreted by T
      cells stimulated with PMA and ionomycin were also determined by flow cytometry.
      RESULTS: The percentage of CD4(+)CD25(high)CD127(-/dim)CD62L(+) Treg cells was
      significantly higher in the G-BM group, with higher proportions of CD45RA(+)
      naive Treg cells and higher expression of CD69 on Treg cells in G-BM (P < 0.05).
      The percentage of Ki67 expression in CD4(+)CD25(high)Foxp3(+) Treg cells in G-BM
      was significantly higher than that on G-PB. The suppressive functions of Treg
      cells in inhibiting T-cell activation were comparable between G-BM and G-PB. The
      proportions of CD4(+)CD25(-)CD69(+) Treg subsets as well as Th1 cells in G-BM
      were also significantly higher than those in G-PB (P < 0.001). The proportions of
      conventional T cells and Th17 effector cells were comparable in G-BM compared
      with those in G-PB. Thus, the ratio of conventional T cells and
      CD4(+)CD25(high)CD127(-/dim) regulatory T cells were lower in G-BM than that in G
      PB (P = 0.014). CONCLUSION: In addition to the much higher T-cell counts in G-PB
      grafts that may contribute to more severe GVHD, the higher frequency of Treg
      cells and lower ratio of conventional T cells to Treg cells in G-BM compared with
      G-PB grafts might reduce GVHD post-transplantation in G-BM compared with G-PB
      transplantation.

PMID- 25948101
TI  - Dasotraline for the Treatment of Attention-Deficit/Hyperactivity Disorder: A
      Randomized, Double-Blind, Placebo-Controlled, Proof-of-Concept Trial in Adults.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder
      characterized by symptoms of inattention, hyperactivity, and impulsivity
      associated with clinically significant impairment in functioning. ADHD has an
      early onset, but frequently persists, with a prevalence estimate of 4% in adults.
      Dasotraline is a novel compound that is a potent inhibitor of dopamine and
      norepinephrine transporters that achieves stable plasma concentrations with once
      daily dosing. In this study, adult outpatients meeting DSM-IV-TR criteria for
      ADHD were randomized to 4 weeks of double-blind, once-daily treatment with
      dasotraline 4 and 8 mg/day or placebo. The primary efficacy end point was change
      from baseline at week 4 in the ADHD Rating Scale, Version IV (ADHD RS-IV) total
      score. Secondary efficacy end points included the Clinical Global Impression,
      Severity (CGI-S) scale, modified for ADHD symptoms. Least squares (LS) mean
      improvements at week 4 in ADHD RS-IV total score were significantly greater for
      dasotraline 8 mg/day vs placebo (-13.9 vs -9.7; P=0.019), and nonsignificantly
      greater for 4 mg/day (-12.4; P=0.076). The LS mean improvements in modified CGI-S
      were significantly greater at week 4 for dasotraline 8 mg/day vs placebo (-1.1 vs
      -0.7; P=0.013), and for 4 mg/day vs placebo (-1.1 vs -0.7; P=0.021). The most
      frequent adverse events reported were insomnia, decreased appetite, nausea, and
      dry mouth. Discontinuations due to treatment-emergent adverse events were 10.3%
      and 27.8% of patients in 4 and 8 mg/day treatment groups, respectively. This
      study provides preliminary evidence that once-daily dosing with dasotraline, a
      long-acting, dual monoamine reuptake inhibitor, may be a safe and efficacious
      treatment for adult ADHD. 

PMID- 25948102
TI  - Dietary n-3 PUFAs Deficiency Increases Vulnerability to Inflammation-Induced
      Spatial Memory Impairment.
AB  - Dietary n-3 polyunsaturated fatty acids (PUFAs) are critical components of
      inflammatory response and memory impairment. However, the mechanisms underlying
      the sensitizing effects of low n-3 PUFAs in the brain for the development of
      memory impairment following inflammation are still poorly understood. In this
      study, we examined how a 2-month n-3 PUFAs deficiency from pre-puberty to
      adulthood could increase vulnerability to the effect of inflammatory event on
      spatial memory in mice. Mice were given diets balanced or deficient in n-3 PUFAs
      for a 2-month period starting at post-natal day 21, followed by a peripheral
      administration of lipopolysaccharide (LPS), a bacterial endotoxin, at adulthood.
      We first showed that spatial memory performance was altered after LPS challenge
      only in n-3 PUFA-deficient mice that displayed lower n-3/n-6 PUFA ratio in the
      hippocampus. Importantly, long-term depression (LTD), but not long-term
      potentiation (LTP) was impaired in the hippocampus of LPS-treated n-3 PUFA
      deficient mice. Proinflammatory cytokine levels were increased in the plasma of
      both n-3 PUFA-deficient and n-3 PUFA-balanced mice. However, only n-3 PUFA
      balanced mice showed an increase in cytokine expression in the hippocampus in
      response to LPS. In addition, n-3 PUFA-deficient mice displayed higher
      glucocorticoid levels in response to LPS as compared with n-3 PUFA-balanced mice.
      These results indicate a role for n-3 PUFA imbalance in the sensitization of the
      hippocampal synaptic plasticity to inflammatory stimuli, which is likely to
      contribute to spatial memory impairment. 

PMID- 25948103
TI  - A CHRNA5 Smoking Risk Variant Decreases the Aversive Effects of Nicotine in
      Humans.
AB  - Genome-wide association studies have implicated the CHRNA5-CHRNA3-CHRNB4 gene
      cluster in risk for heavy smoking and several smoking-related disorders. The
      heavy smoking risk allele might reduce the aversive effects of nicotine, but this
      hypothesis has not been tested in humans. We evaluated the effects of a candidate
      causal variant in CHRNA5, rs16969968, on the acute response to nicotine in
      European American (EA) and African American (AA) smokers (n=192; 50% AA; 73%
      male). Following overnight abstinence from nicotine, participants completed a
      protocol that included an intravenous (IV) dose of saline and two escalating IV
      doses of nicotine. The outcomes evaluated were the aversive, pleasurable, and
      stimulatory ratings of nicotine's effects, cardiovascular reactivity to nicotine,
      withdrawal severity, and cognitive performance before and after the nicotine
      administration session. The heavy smoking risk allele (rs16969968*A;
      frequency=28% (EA) and 6% (AA)) was associated with lower ratings of aversive
      effects (P<5 * 10(-8)) with marked specificity. This effect was evident in EA and
      AA subjects analyzed as separate groups and was most robust at the highest
      nicotine dose. Rs16969968*A was also associated with greater improvement on a
      measure of cognitive control (Stroop Task) following nicotine administration.
      These findings support differential aversive response to nicotine as one likely
      mechanism for the association of CHRNA5-CHRNA3-CHRNB4 with heavy smoking. 

PMID- 25948104
TI  - Transcriptional changes associated with resistance to inhibitors of epidermal
      growth factor receptor revealed using metaanalysis.
AB  - BACKGROUND: EGFR is important in maintaining metabolic homeostasis in healthy
      cells, but in tumors it activates downstream signaling pathways, causing
      proliferation, angiogenesis, invasion and metastasis. Consequently, EGFR is
      targeted in cancers using reversible, irreversible or antibody inhibitors.
      Unfortunately, tumors develop inhibitor resistance by mutations or overexpressing
      EGFR, or its ligand, or activating secondary, EGFR-independent pathways. METHODS:
      Here we present a global metaanalysis comparing transcriptional profiles from
      matched pairs of EGFR inhibitor-sensitive vs. -resistant cell lines, using 15
      datasets comprising 274 microarrays. We also analyzed separately pairs of cell
      lines derived using reversible, irreversible or antibody inhibitors. RESULTS: The
      metaanalysis identifies commonalities in cell lines resistant to EGFR inhibitors:
      in sensitive cell lines, the ontological categories involving the ErbB receptors
      pathways, cell adhesion and lipid metabolism are overexpressed; however,
      resistance to EGFR inhibitors is associated with overexpression of genes for ErbB
      receptors-independent oncogenic pathways, regulation of cell motility, energy
      metabolism, immunity especially inflammatory cytokines biosynthesis, cell cycle
      and responses to exogenous and endogenous stimuli. Specifically in Gefitinib
      resistant cell lines, the immunity-associated genes are overexpressed, whereas in
      Erlotinib-resistant ones so are the mitochondrial genes and processes.
      Unexpectedly, lines selected using EGFR-targeting antibodies overexpress
      different gene ontologies from ones selected using kinase inhibitors.
      Specifically, they have reduced expression of genes for proliferation,
      chemotaxis, immunity and angiogenesis. CONCLUSIONS: This metaanalysis suggests
      that 'combination therapies' can improve cancer treatment outcomes. Potentially,
      use of mitochondrial blockers with Erlotinib, immunity blockers with Gefitinib,
      tyrosine kinase inhibitors with antibody inhibitors, may have better chance of
      avoiding development of resistance.

PMID- 25948106
TI  - Presentation and diagnosis of adult-onset Still's disease: the implications of
      current and emerging markers in overcoming the diagnostic challenge.
AB  - Adult-onset Still's disease (AOSD) is a known cause of fever of unknown origin.
      It is characterized by a triad of symptoms: spiking fever (>39 degrees C), salmon
      colored rash and arthritis/arthralgia. On a predisposing genetic background,
      several conditions may act as trigger for disease and among these, infectious
      agents are the most important. Nowadays, a dichotomous view of AOSD has been
      introduced which distinguishes this entity in two subsets according to the
      clinical features and laboratory aspects: systemic or articular. As AOSD is a
      diagnosis of exclusion, specific biomarkers able to facilitate differential
      diagnosis are needed. A number of possible biomarkers have been proposed that
      will be discussed in detail in this review: ferritin, IL-18, procalcitonin, s100
      proteins and sCD163. 

PMID- 25948105
TI  - Baicalein increases the expression and reciprocal interplay of RUNX3 and FOXO3a
      through crosstalk of AMPKalpha and MEK/ERK1/2 signaling pathways in human non
      small cell lung cancer cells.
AB  - BACKGROUND: Baicalein, a natural flavonoid obtained from the Scutellaria
      baicalensis root, has been reported to inhibit growth of human lung cancer.
      However, the detailed mechanism underlying this has not been well elucidated.
      METHODS: Cell viability was measured using a 3-(4, 5-dimethylthiazol-2-yl)-2, 5
      diphenyltetrazolium bromide (MTT) assays. Apoptosis was detected by flow
      cytometry analysis and caspase 3/7 assays. The expression of RUNX3 and FOXO3a
      mRNA were measured by real time RT-PCR methods. Western blot analysis was
      performed to measure the phosphorylation and protein expression of AMP-activated
      protein kinase alpha (AMPKalpha) and extracellular signal-regulated kinase 1/2
      (ERK1/2), runt-related transcription factor 3 (RUNX3) and forkhead box O3a
      (FOXO3a). Silencing of FOXO3a and RUNX3 were performed by small interfering RNA
      (siRNA) methods. Exogenous expression of FOXO3a or RUNX3 was carried out by
      electroporated transfection assays. RESULTS: We showed that baicalein
      significantly inhibited growth and induced apoptosis of non-small cell lung
      cancer (NSCLC) cells in a time- and dose-dependent manner. Baicalein induced
      RUNX3 and FOXO3a protein expression, and increased phosphorylation of AMPKalpha
      and ERK1/2. Moreover, the inhibitors of AMPK and MEK/ERK1/2 reversed the effect
      of baicalein on RUNX3 and FOXO3a protein expression. Interestingly, while
      compound C had little effect on blockade of baicalein-induced phosphorylation of
      ERK1/2, PD98059 significantly abrogated baicalein-induced phosphorylation of
      AMPKalpha. Intriguingly, while silencing of RUNX3 abolished the effect of
      baicalein on expression of FOXO3a and apoptosis, silencing of FOXO3a
      significantly attenuated baicalein-reduced cell proliferation. On the contrary,
      overexpression of FOXO3a restored the effect of baicalein on cell growth
      inhibition in cells silencing of endogenous FOXO3a gene and enhanced the effect
      of baicalein on RUNX3 protein expression. Finally, exogenous expression of RUNX3
      increased FOXO3a protein and strengthened baicalein-induced phosphorylation of
      ERK1/2. CONCLUSION: Collectively, our results show that baicalein inhibits growth
      and induces apoptosis of NSCLC cells through AMPKalpha- and MEK/ERK1/2-mediated
      increase and interaction of FOXO3a and RUNX3 protein. The crosstalk between
      AMPKalpha and MEK/ERK1/2 signaling pathways, and the reciprocal interplay of
      FOXO3a and RUNX3 converge on the overall response of baicalein. This study
      reveals a novel mechanism for regulating FOXO3a and RUNX3 signaling axis in
      response to baicalein and suggests a new strategy for NSCLC associated targeted
      therapy.

PMID- 25948107
TI  - Skeletal and cardiac muscle involvement in children with glycogen storage disease
      type III.
AB  - Glycogen storage disease type III (GSD III) may present with hepatic disease or
      may involve both skeletal and cardiac muscles as well. To assess the prevalence
      of neuromuscular and cardiac involvement in a group of children with GSD III, 28
      children with GSD III, diagnosed by enzymatic assay, were enrolled in the study
      after an informed consent was obtained from their parents/guardians and after the
      study protocol was approved by our institutional ethical committee. Their mean
      age was 6.6 + 3.1 years. All cases were assessed neurologically by clinical
      examination, electromyography (EMG), and nerve conduction velocity. The heart was
      examined clinically by electrocardiogram and echocardiography. Seventeen patients
      (61 %) had myopathic changes by EMG, three of them had associated neuropathic
      changes. Creatine phosphokinase (CPK) was elevated in all myopathic cases except
      one. Children with myopathic changes were significantly older (p = 0.02), and CPK
      was significantly higher (p < 0.0001). Nine cases had left ventricular (LV)
      hypertrophy, seven of them had myopathic changes by EMG. CONCLUSION: Myopathic
      changes are not uncommon in children with GSD III. Myopathic changes tend to
      occur in older age and are associated with higher CPK level. Cardiac muscle
      involvement is less common in this age group and may, on occasion, occur alone
      without skeletal muscle involvement. Despite mild degrees of affection in this
      age group, it is recommended to perform prospective annual screening using EMG
      and echocardiography in order to augment dietary therapy regimen to prevent
      progression to life threatening complications.

PMID- 25948108
TI  - Three cases with L1 syndrome and two novel mutations in the L1CAM gene.
AB  - Mutations in the L1CAM gene have been identified in the following various X
      linked neurological disorders: congenital hydrocephalus; mental retardation,
      aphasia, shuffling gait, and adducted thumbs (MASA) syndrome; spastic paraplegia;
      and agenesis of the corpus callosum. These conditions are currently considered
      different phenotypes of a single entity known as L1 syndrome. We present three
      families with L1 syndrome. Sequencing of the L1CAM gene allowed the
      identification of the following mutations involved: a known splicing mutation
      (c.3531-12G>A) and two novel ones: a missense mutation (c.1754A>C; p.Asp585Ala)
      and a nonsense mutation (c.3478C>T; p.Gln1160Stop). The number of affected males
      and carrier females identified in a relatively small population suggests that L1
      syndrome may be under-diagnosed. CONCLUSION: L1 syndrome should be considered in
      the differential diagnosis of intellectual disability or mental retardation in
      children, especially when other signs such as hydrocephalus or adducted thumbs
      are present.

PMID- 25948109
TI  - Digoxin is linked to raised risk of death in patients with atrial fibrillation.

PMID- 25948110
TI  - Heat shock protein 90 mediates the apoptosis and autophage in nicotinic
      mycoepoxydiene-treated HeLa cells.
AB  - Heat shock protein 90 (Hsp90) is a fascinating target for cancer therapy due to
      its significant role in the crossroad of multiple signaling pathways associated
      with cell proliferation and regulation. Hsp90 inhibitors have the potential to be
      developed into anti-cancer drugs. Here, we identified nicotinic-mycoepoxydiene
      (NMD), a structurally novel compound as Hsp90 inhibitor to perform the anti-tumor
      activity. The compound selectively bound to the Hsp90 N-terminal domain, and
      degraded the Hsp90 client protein Akt. The degradation of Akt detained Bad in non
      phosphorylation form. NMD-associated apoptosis was characterized by the formation
      of fragmented nuclei, poly(ADP-ribose) polymerase cleavage, cytochrome c release,
      caspase-3 activation, and the increased proportion of sub-G1 phase cells.
      Interestingly, the apoptosis was accompanied with autophagy, by exhibiting the
      increased expression of LC-3 and the decrease of lysosome pH value. Our findings
      provide a novel cellular mechanism by which Hsp90 inhibitor adjusts cell
      apoptosis and autophagy in vitro, suggesting that NMD not only has a potential to
      be developed into a novel anti-tumor pharmaceutical, but also exhibits a new
      mechanism in regulating cancer cell apoptosis and autophagy via Hsp90 inhibition.

PMID- 25948111
TI  - Defining the relationship between Plasmodium vivax parasite rate and clinical
      disease.
AB  - BACKGROUND: Though essential to the development and evaluation of national
      malaria control programmes, precise enumeration of the clinical illness burden of
      malaria in endemic countries remains challenging where local surveillance systems
      are incomplete. Strategies to infer annual incidence rates from parasite
      prevalence survey compilations have proven effective in the specific case of
      Plasmodium falciparum, but have yet to be developed for Plasmodium vivax.
      Moreover, defining the relationship between P. vivax prevalence and clinical
      incidence may also allow levels of endemicity to be inferred for areas where the
      information balance is reversed, that is, incident case numbers are more widely
      gathered than parasite surveys; both applications ultimately facilitating
      cartographic estimates of P. vivax transmission intensity and its ensuring
      disease burden. METHODS: A search for active case detection surveys was conducted
      and the recorded incidence values were matched to local, contemporary parasite
      rate measures and classified to geographic zones of differing relapse phenotypes.
      A hierarchical Bayesian model was fitted to these data to quantify the
      relationship between prevalence and incidence while accounting for variation
      among relapse zones. RESULTS: The model, fitted with 176 concurrently measured P.
      vivax incidence and prevalence records, was a linear regression of the logarithm
      of incidence against the logarithm of age-standardized prevalence. Specific
      relationships for the six relapse zones where data were available were drawn, as
      well as a pooled overall relationship. The slope of the curves varied among
      relapse zones; zones with short predicted time to relapse had steeper slopes than
      those observed to contain long-latency relapse phenotypes. CONCLUSIONS: The
      fitted relationships, along with appropriate uncertainty metrics, allow for
      estimates of clinical incidence of known confidence to be made from wherever P.
      vivax prevalence data are available. This is a prerequisite for cartographic
      based inferences about the global burden of morbidity due to P. vivax, which will
      be used to inform control efforts.

PMID- 25948114
TI  - Lumbar spinal epidural arteriovenous fistula with perimedullary venous drainage
      after endoscopic lumbar surgery.
AB  - Spinal epidural arteriovenous fistulas (AVFs) with perimedullary venous drainage
      are rare. This report describes a case of lumbar epidural AVF in a patient with a
      history of endoscopic lumbar discectomy at the same level 8 years prior to
      presenting with progressive myelopathy secondary to retrograde venous reflux into
      the perimedullary vein. A 69-year-old man presented with progressive lower
      extremity weakness and sensory disturbance and loss of sphincter control 8 years
      after endoscopic lumbar discectomy for a disc herniation at L4-5 level. Magnetic
      resonance imaging showed spinal cord edema and dilated intradural perimedullary
      vessels. Spinal angiography revealed an epidural AVF at the site of the previous
      endoscopic lumbar surgery with intradural perimedullary venous drainage. The
      fistula was successfully occluded via endovascular transarterial embolization,
      and the patient had stabilization of his neurological deficits. Lumbar spinal
      epidural AVFs, especially those associated with iatrogenic trauma, are rare.
      Endoscopic surgical procedure can occlude the epidural venous plexus and disturb
      venous drainage, thereby inducing local venous hypertension and leading to
      epidural AVF with perimedullary venous drainage. This type of pathology should be
      considered within the differential diagnosis of delayed neurological
      deterioration after spinal surgery. 

PMID- 25948112
TI  - Pre-diagnostic concordance with the WCRF/AICR guidelines and survival in European
      colorectal cancer patients: a cohort study.
AB  - BACKGROUND: Cancer survivors are advised to follow lifestyle recommendations on
      diet, physical activity, and body fatness proposed by the World Cancer Research
      Fund/American Institute of Cancer Research (WCRF/AICR) for cancer prevention.
      Previous studies have demonstrated that higher concordance with these
      recommendations measured using an index score (the WCRF/AICR score) was
      associated with lower cancer incidence and mortality. The aim of this study was
      to evaluate the association between pre-diagnostic concordance with WCRF/AICR
      recommendations and mortality in colorectal cancer (CRC) patients. METHODS: The
      association between the WCRF/AICR score (score range 0-6 in men and 0-7 in women;
      higher scores indicate greater concordance) assessed on average 6.4 years before
      diagnosis and CRC-specific (n = 872) and overall mortality (n = 1,113) was
      prospectively examined among 3,292 participants diagnosed with CRC in the
      European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (mean
      follow-up time after diagnosis 4.2 years). Multivariable Cox proportional hazard
      models were used to estimate hazard ratios (HRs) and 95% confidence intervals
      (CIs) for mortality. RESULTS: The HRs (95% CIs) for CRC-specific mortality among
      participants in the second (score range in men/women: 2.25-2.75/3.25-3.75), third
      (3-3.75/4-4.75), and fourth (4-6/5-7) categories of the score were 0.87 (0.72
      1.06), 0.74 (0.61-0.90), and 0.70 (0.56-0.89), respectively (P for trend
      <0.0001), compared to participants with the lowest concordance with the
      recommendations (category 1 of the score: 0-2/0-3). Similar HRs for overall
      mortality were observed (P for trend 0.004). Meeting the recommendations on body
      fatness and plant food consumption were associated with improved survival among
      CRC cases in mutually adjusted models. CONCLUSIONS: Greater concordance with the
      WCRF/AICR recommendations on diet, physical activity, and body fatness prior to
      CRC diagnosis is associated with improved survival among CRC patients.

PMID- 25948113
TI  - A novel insight into the cost-benefit model for the evolution of botanical
      carnivory.
AB  - BACKGROUND: The cost-benefit model for the evolution of botanical carnivory
      provides a conceptual framework for interpreting a wide range of comparative and
      experimental studies on carnivorous plants. This model assumes that the modified
      leaves called traps represent a significant cost for the plant, and this cost is
      outweighed by the benefits from increased nutrient uptake from prey, in terms of
      enhancing the rate of photosynthesis per unit leaf mass or area (AN) in the
      microsites inhabited by carnivorous plants. SCOPE: This review summarizes results
      from the classical interpretation of the cost-benefit model for evolution of
      botanical carnivory and highlights the costs and benefits of active trapping
      mechanisms, including water pumping, electrical signalling and accumulation of
      jasmonates. Novel alternative sequestration strategies (utilization of leaf
      litter and faeces) in carnivorous plants are also discussed in the context of the
      cost-benefit model. CONCLUSIONS: Traps of carnivorous plants have lower AN than
      leaves, and the leaves have higher AN after feeding. Prey digestion, water
      pumping and electrical signalling represent a significant carbon cost (as an
      increased rate of respiration, RD) for carnivorous plants. On the other hand,
      jasmonate accumulation during the digestive period and reprogramming of gene
      expression from growth and photosynthesis to prey digestion optimizes enzyme
      production in comparison with constitutive secretion. This inducibility may have
      evolved as a cost-saving strategy beneficial for carnivorous plants. The
      similarities between plant defence mechanisms and botanical carnivory are
      highlighted.

PMID- 25948115
TI  - Endovascular management of a collateral network aneurysm in a patient with
      spontaneous internal carotid artery occlusion.
AB  - Spontaneous "non-moyamoya" arterial occlusion of the intracranial arteries is
      very unusual. Progressive occlusion of a major intracranial artery, independently
      from the etiology, can lead to the development of collateral arterial networks
      that supply blood flow to distal territories beyond the occlusion. These
      collateral arteries are typically small and conduct low flows, but the
      hemodynamic stress within them can lead to aneurysm formation within the
      collateral network. In this report we present a case of spontaneous internal
      carotid artery occlusion and collateral network aneurysm for the first time in
      the literature and discuss the main features of the etiology and endovascular
      treatment of this rare, challenging aneurysm. 

PMID- 25948116
TI  - Isolated, but transnational: the glocal nature of Waldensian ethnobotany, Western
      Alps, NW Italy.
AB  - BACKGROUND: An ethnobotanical field study on the traditional uses of wild plants
      for food as well as medicinal and veterinary plants was conducted in four
      Waldensian valleys (Chisone, Germanasca, Angrogna, and Pellice) in the Western
      Alps, Piedmont, NW Italy. Waldensians represent a religious Protestant Christian
      minority that originated in France and spread around 1,170 AD to the Italian side
      of Western Alps, where, although persecuted for centuries, approximately 20,000
      believers still survive today, increasingly mixing with their Catholic
      neighbours. METHODS: Interviews with a total of 47 elderly informants, belonging
      to both Waldensian and Catholic religious groups, were undertaken in ten Western
      Alpine villages, using standard ethnobotanical methods. RESULTS: The uses of 85
      wild and semi-domesticated food folk taxa, 96 medicinal folk taxa, and 45
      veterinary folk taxa were recorded. Comparison of the collected data within the
      two religious communities shows that Waldensians had, or have retained, a more
      extensive ethnobotanical knowledge, and that approximately only half of the wild
      food and medicinal plants are known and used by both communities. Moreover, this
      convergence is greater for the wild food plant domain. Comparison of the
      collected data with ethnobotanical surveys conducted at the end of the 19th
      Century and the 1980s in one of studied valleys (Germanasca) shows that the
      majority of the plants recorded in the present study are used in the same or
      similar ways as they were decades ago. Idiosyncratic plant uses among Waldensians
      included both archaic uses, such as the fern Botrychium lunaria for skin
      problems, as well as uses that may be the result of local adaptions of Central
      and Northern European customs, including Veronica allionii and V. officinalis as
      recreational teas and Cetraria islandica in infusions to treat coughs.
      CONCLUSIONS: The great resilience of plant knowledge among Waldensians may be the
      result of the long isolation and history of marginalisation that this group has
      faced during the last few centuries, although their ethnobotany present trans
      national elements. Cross-cultural and ethno-historical approaches in ethnobotany
      may offer crucial data for understanding the trajectory of change of plant
      knowledge across time and space.

PMID- 25948118
TI  - Effect of crude oil exposure and dispersant application on meiofauna: an
      intertidal mesocosm experiment.
AB  - Dispersant application is used as a response technique to minimize the
      environmental risk of an oil spill. In nearshore areas, dispersant application is
      a controversial countermeasure: environmental benefits are counteracted by the
      toxicity of dispersant use. The effects of the use of chemical dispersants on
      meiobenthic organisms and nematodes were investigated in a mesocosm experiment. A
      20 day experiment was performed in four experimental sets of mesocosms. In three
      of them, sediments were contaminated, respectively by oil (500 mg kg(-1)),
      dispersed oil (oil + 5% dispersant), and dispersant alone, whereas in the last
      set sediments were kept undisturbed and used as a reference (Re). Our results
      showed that the meiobenthic response to oil contamination was rapid, for copepods
      and nematodes. One-way ANOVA showed a significant decrease of the abundance of
      copepods. In the case of nematodes, univariate and multivariate analyses
      indicated a clear decrease of the abundance of the species after only 20 days of
      pollutant exposure and thus reducing Shannon-Wiener diversity and Pielou's
      evenness. In contrast, Sphaerolaimus gracilis and Sabateria sp. became more
      frequent within disturbed assemblages and appeared to be resistant and/or
      opportunistic species in the presence of these kinds of toxicants. Moreover,
      responses of copepods and nematodes to the treatment seemed to be the same
      irrespective of whether only oil or oil + dispersant was performed. The main
      toxicities of dispersed oil come not from the "composition of a newly formed oil
      and oil spill dispersant mixture" but from the "quantities of increased dispersed
      oil droplets". 

PMID- 25948117
TI  - Improved quality of life among adolescents with attention-deficit/hyperactivity
      disorder is mediated by protective factors: a cross sectional survey.
AB  - BACKGROUND: The aim of this study was to assess the role of protective factors as
      mediators and/or moderators of the relationship between coexisting emotional and
      conduct problems and quality of life (QoL) among adolescents with attention
      deficit/hyperactivity disorder (ADHD). METHODS: The sample consisted of 194
      adolescents with ADHD. Participants completed measures of individual
      competencies, family cohesion and social support, and QoL. Coexisting emotional
      and conduct problems were assessed using the Strength and Difficulties
      Questionnaire. RESULTS: Individual competencies and social support mediated the
      association between emotional and conduct problems and QoL. Family cohesion was
      associated with both emotional and conduct problems. No moderating effects of
      protective factors and coexisting problems were found. CONCLUSIONS: The
      assessment of individual competencies, social resources, and family cohesion may
      identify potential treatment goals for adolescents with ADHD and coexisting
      problems, and may contribute to improvements in QoL.

PMID- 25948119
TI  - Identification by microarray technology of key genes involved in the progression
      of carotid atherosclerotic plaque.
AB  - A comparative analysis of gene expression profiles between early and advanced
      carotid atherosclerotic plaque was performed to identify key genes and pathways
      involved in the progression of carotid atherosclerotic plaque. Gene expression
      data set GSE28829 was downloaded from Gene Expression Omnibus, including 13 early
      and 16 advanced atherosclerotic plaque samples from human carotid. Differentially
      expressed genes (DEGs) were identified using the package limma of R. Principal
      component analysis was carried out for the DEGs with package rgl of R. A gene
      coexpression network was constructed with information from COXPRESdb and then
      visualized with Cytoscape. Functional enrichment analysis was performed with
      DAVID and pathway enrichment analysis was done with KEGG. A total of 319 DEGs
      were identified in the advanced atherosclerotic plaque samples compared with
      early atherosclerotic plaque samples, including 267 up-regulated genes and 52
      down-regulated genes. In the gene coexpression network, TYRO protein tyrosine
      kinase binding protein was the hub gene with a degree of 23. Functional
      enrichment analysis and pathway enrichment analysis suggested that the immune
      response played a critical role in the progression of carotid atherosclerotic
      plaque. A number of key genes were revealed in carotid atherosclerotic plaque,
      and are potential biomarkers for diagnosis or treatment. These findings may also
      guide future research to better decipher the progression of atherosclerosis. 

PMID- 25948120
TI  - Protein-protein interaction prediction by combined analysis of genomic and
      conservation information.
AB  - Protein-protein interactions (PPIs) are highly important because of their main
      role in cellular processes and biochemical pathways; therefore, PPI can be very
      useful in the prediction of protein functions. Experimental techniques of PPI
      detection have certain drawbacks; hence computational methods can be used to
      complement wet lab techniques. Such methods can be applied to PPI prediction as
      well as validation of experimental results. Computational algorithms can lead to
      many false PPI predictions, which in turn result in non-adequate performance. We
      have developed a novel method based on combined analysis, entitled PPIccc. Three
      different descriptors for PPIccc included gene co-expression values, codon usage
      similarity and conservation of surface residues between protein products of a
      gene pair, which combined to predict PPI. Validation of results based on Human
      Protein Reference Database (HPRD) indicated improvement of performance in our
      proposed method. The results also revealed that conservation of surface residues
      between proteins in combination with codon usage similarity of their related
      genes increase the performance of PPI prediction. This means that codon usage
      similarity and surface residues between proteins (only sequence-based features)
      can predict PPIs as good as PPIccc. 

PMID- 25948125
TI  - Can new diagnostic criteria of rheumatoid arthritis really make an early
      diagnosis? --A case report of early diagnosis and treatment of early rheumatoid
      arthritis with Chinese medicine.

PMID- 25948124
TI  - Effect of yangxinkang tablets on chronic heart failure: A multi-center randomized
      double-blind placebo-controlled trial.
AB  - OBJECTIVES: To investigate the safety and efficacy of yangxinkang tablets in
      patients with chronic heart failure (CHF) and syndrome of qi and yin deficiency,
      blood stasis, and water retention. METHODS: In a double-blinded, randomized,
      placebo-controlled, multicenter clinical trail, 228 patients with CHF New York
      Heart Association (NYHA) class II or III in stage C were assigned by randomized
      block method to two groups in a 1:1 ratio to undergo either conventional Western
      treatment or conventional treatment plus yangxinkang tablets for 4 weeks. The
      outcome measure were effect of cardiac function, Chinese medicine (CM) syndromes,
      scores of symptoms, signs, and quality of life measured by Minnesota Living with
      heart failure questionnaire (MLHFQ) before and after the treatment. RESULTS:
      Totally 112 patients were analyzed in the treatment group and 109 in the control
      group. They were comparable in NYHA functional class, basic parameters and
      primary diseases before treatment. Cardiac function and CM syndromes were greatly
      ameliorated in both groups after treatment. Total effective rates of cardiac
      function and CM syndrome in the treatment group were significantly higher than
      those in the control group (P<0.05). Total symptom score and sign score in the
      treatment group decreased significantly after treatment (P<0.01), which were
      significantly lower than those in the control group (P<0.05). There were
      statistically significant differences in post-treatment scores of gasp, cough
      with phlegm, pulmonary rales and jugular vein engorgement between the two groups
      (P<0.05 or P<0.01). Three MLHFQ scores decreased significantly in both groups
      after treatment (P<0.01). Post-treatment total scale score and physical subscale
      score in the treatment group and the reduction of them showed statistically
      significant differences (P<0.05) as compared with the control group. There was no
      significant difference between the two groups in emotional subscale score and the
      reduction after treatment (P>0.05). There was no obvious adverse reaction in
      either group noted during the study. CONCLUSIONS: Yangxinkang tablets were safe
      and efficacious in improving cardiac function, CM syndromes, symptoms, signs, and
      quality of life in patients with CHF class II or III in stage C on the base of
      conventional treatment.

PMID- 25948127
TI  - "Right tool," wrong "job": Manual vacuum aspiration, post-abortion care and
      transnational population politics in Senegal.
AB  - The "rightness" of a technology for completing a particular task is negotiated by
      medical professionals, patients, state institutions, manufacturing companies, and
      non-governmental organizations. This paper shows how certain technologies may
      challenge the meaning of the "job" they are designed to accomplish. Manual vacuum
      aspiration (MVA) is a syringe device for uterine evacuation that can be used to
      treat complications of incomplete abortion, known as post-abortion care (PAC), or
      to terminate pregnancy. I explore how negotiations over the rightness of MVA as
      well as PAC unfold at the intersection of national and global reproductive
      politics during the daily treatment of abortion complications at three hospitals
      in Senegal, where PAC is permitted but induced abortion is legally prohibited.
      Although state health authorities have championed MVA as the "preferred" PAC
      technology, the primary donor for PAC, the United States Agency for International
      Development, does not support the purchase of abortifacient technologies. I
      conducted an ethnography of Senegal's PAC program between 2010 and 2011. Data
      collection methods included interviews with 49 health professionals, observation
      of PAC treatment and review of abortion records at three hospitals, and a review
      of transnational literature on MVA and PAC. While MVA was the most frequently
      employed form of uterine evacuation in hospitals, concerns about off-label MVA
      practices contributed to the persistence of less effective methods such as
      dilation and curettage (D&C) and digital curettage. Anxieties about MVA's
      capacity to induce abortion have constrained its integration into routine
      obstetric care. This capacity also raises questions about what the "job," PAC,
      represents in Senegalese hospitals. The prioritization of MVA's security over
      women's access to the preferred technology reinforces gendered inequalities in
      health care. 

PMID- 25948131
TI  - Statin-associated muscle injury.

PMID- 25948132
TI  - Gadamerian philosophical hermeneutics as a useful methodological framework for
      the Delphi technique.
AB  - In this article we aim to demonstrate how Gadamerian philosophical hermeneutics
      may provide a sound methodological framework for researchers using the Delphi
      Technique (Delphi) in studies exploring health and well-being. Reporting of the
      use of Delphi in health and well-being research is increasing, but less attention
      has been given to covering its methodological underpinnings. In Delphi, a
      structured anonymous conversation between participants is facilitated, via an
      iterative survey process. Participants are specifically selected for their
      knowledge and experience with the topic of interest. The purpose of structuring
      conversation in this manner is to cultivate collective opinion and highlight
      areas of disagreement, using a process that minimizes the influence of group
      dynamics. The underlying premise is that the opinion of a collective is more
      useful than that of an individual. In designing our study into health literacy,
      Delphi aligned well with our research focus and would enable us to capture
      collective views. However, we were interested in the methodology that would
      inform our study. As researchers, we believe that methodology provides the
      framework and principles for a study and is integral to research integrity. In
      assessing the suitability of Delphi for our research purpose, we found little
      information about underpinning methodology. The absence of a universally
      recognized or consistent methodology associated with Delphi was highlighted
      through a scoping review we undertook to assist us in our methodological
      thinking. This led us to consider alternative methodologies, which might be
      congruent with the key principles of Delphi. We identified Gadamerian
      philosophical hermeneutics as a methodology that could provide a supportive
      framework and principles. We suggest that this methodology may be useful in
      health and well-being studies utilizing the Delphi method. 

PMID- 25948133
TI  - Formation of Halogen Bond-Based 2D Supramolecular Assemblies by Electric
      Manipulation.
AB  - Halogen bonding has attracted much attention recently as an important driving
      force for supramolecular assembly and crystal engineering. Herein, we demonstrate
      for the first time the formation of a halogen bond-based open porous network on a
      graphite surface using ethynylpyridine and aryl-halide based building blocks. We
      found that the electrical stimuli of a scanning tunneling microscopy (STM) tip
      can induce the formation of a binary supramolecular structure on the basis of
      halogen bond formation between terminal pyridyl groups and perfluoro-iodobenzene.
      This electrical manipulation method can be applied to engineer a series of linear
      or porous structures by selecting halogen bond donor and acceptor fragments with
      different symmetries, as the directional interactions ultimately determine the
      structural outcome. 

PMID- 25948135
TI  - A review on green trend for oil extraction using subcritical water technology and
      biodiesel production.
AB  - It became a global agenda to develop clean alternative fuels which were
      domestically available, environmentally acceptable and technically feasible.
      Thus, biodiesel was destined to make a substantial contribution to the future
      energy demands of the domestic and industrial economies. Utilization of the non
      edible vegetable oils as raw materials for biodiesel production had been handled
      frequently for the past few years. The oil content of these seeds could be
      extracted by different oil extraction methods, such as mechanical extraction,
      solvent extraction and by subcritical water extraction technology SWT. Among
      them, SWT represents a new promising green extraction method. Therefore this
      review covered the current used non edible oil seeds for biodiesel production as
      well as giving a sharp focus on the efficiency of using the SWT as a promising
      extraction method. In addition the advantages and the disadvantages of the
      different biodiesel production techniques would be covered. 

PMID- 25948136
TI  - Evaluation of the fatty acid composition of the seeds of Mangifera indica L. and
      their application.
AB  - Mango (Mangifera indica L.), an edible fruit, is one of the main agricultural
      products in many tropical regions. Mango varieties differ in not only fruit shape
      but also aroma, which is an important characteristic. Although the fruit has many
      uses, the seeds are discarded as waste. Therefore, this study aimed to estimate
      the fatty acid content of seed oil of mangoes from different cultivation areas
      (Miyazaki, Japan, and Taiwan), and to evaluate their application in cosmetics.
      Five fatty acids were identified in the mango seed oil. Oleic acid and stearic
      acid were the principal components of mango seed oil obtained from Miyazaki
      (46.1% and 39.8%, respectively) and Taiwan (43.7% and 40.1%, respectively). As a
      cosmetic ingredient, mango seed oil showed good deodorizing effect on both 2
      nonenal and isovaleric acid. The results indicated the potential applications of
      mango seed oil in the cosmetic industry. 

PMID- 25948137
TI  - Short-term menhaden oil rich diet changes renal lipid profile in acute kidney
      injury.
AB  - Weanling male Wistar rats fed a choline-deficient diet develop acute kidney
      injury. Menhaden oil, which is a very important source of omega-3 fatty acids,
      has a notorious protective effect. The mechanism of this protection is unknown;
      one possibility could be that menhaden oil changes renal lipid profile, with an
      impact on the functions of biological membranes. The aim of this work was to
      study the renal lipid profile in rats fed a choline-deficient diet with menhaden
      oil or vegetable oil as lipids. Rats were divided into 4 groups and fed four
      different diets for 7 days: choline-deficient or choline-supplemented diets with
      corn and hydrogenated oils or menhaden oil. Serum homocysteine, vitamin B12, and
      folic acid were analyzed. Renal lipid profile, as well as the fatty acid
      composition of the three oils, was measured. Choline-deficient rats fed vegetable
      oils showed renal cortical necrosis. Renal omega-6 fatty acids were higher in
      rats fed a cholinedeficient diet and a choline-supplemented diet with vegetable
      oils, while renal omega-3 fatty acids were higher in rats fed a choline-deficient
      diet and a choline-supplemented diet with menhaden oil. Rats fed menhaden oil
      diets had higher levels of renal eicosapentaenoic and docosahexaenoic acids.
      Renal myristic acid was increased in rats fed menhaden oil. The lipid renal
      profile varied quickly according to the type of oil present in the diet. 

PMID- 25948138
TI  - Combination of Novozym 435-catalyzed enantioselective hydrolysis and amidation
      for the preparation of optically active delta-hexadecalactone.
AB  - A new enzymatic method for synthesis of enantiomerically enriched delta
      hexadecalactone (3) based on the enzymatic kinetic resolution of N-methyl-5
      acetoxyhexadecanamide (1) is described. A combination of lipase-catalyzed
      hydrolysis and amidation improved enantioselectivity. Lipase-catalyzed amidation
      was also investigated. Detailed screening of solvents and additive amines was
      performed. The addition of cyclohexylamine to lipase-catalyzed hydrolysis
      afforded the best results to give both enantiomers of 3 with more than 90%
      enantiomeric excess. 

PMID- 25948139
TI  - Evaluation of a new hardness tester (Cariotester): Comparison with transverse
      microradiography for assessing the inhibitory effect of fluoride application on
      bovine root dentin demineralization.
AB  - The objective of this study was to investigate the correlation between CT depth,
      indentation depth determined by a new hardness tester (Cariotester), and the
      transverse microradiography (TMR) parameters, i.e., lesion depth and mineral
      loss. For that purpose, this study evaluated the feasibility of using Cariotester
      as a root caries diagnostic system and capability of Cariotester to detect effect
      of fluoride application on inhibiting dentin demineralization. Fluorides were
      applied to bovine root dentin specimens, which were subsequently demineralized
      for 1-21 days and then CT depth and TMR parameters were assessed. There were
      significant correlations between CT depth and TMR parameters in fluoride and non
      fluoride groups. There were significant differences between fluoride and non
      fluoride groups for CT depth and TMR parameters respectively. Current results
      suggested that Cariotester may be capable of providing an objective evaluation of
      root caries progression and the fluoride effect on inhibiting dentin
      demineralization. 

PMID- 25948140
TI  - Improving biocompatibility of zirconia surface by incorporating Ca ions.
AB  - Though zirconia has been used in dental implant fixtures, the biocompatibility of
      the zirconia surface is not optimal for the surrounding tissue, and many surface
      modifications have been attempted. We have developed a novel method for improving
      the biocompatibility of zirconia by incorporating Ca ions. Elemental analysis
      showed that calcium ions become thoroughly incorporated into the zirconia surface
      after firing with calcium acetate. Mechanical tests indicated that the Ca ions
      had little effect on the flexural strength and hardness. Moreover, incorporating
      Ca ions also dramatically improved the water wettability of specimens that had
      been soaked in a simulated body fluid. The surface of the Ca-modified zirconia
      demonstrated good initial cell attachment. 

PMID- 25948141
TI  - Odontogenic effects of a fast-setting calcium-silicate cement containing
      zirconium oxide.
AB  - A fast-setting calcium-silicate cement (Endocem) was introduced in the field of
      dentistry for use in vital pulp therapy. Similar to mineral trioxide aggregate
      (MTA), it contains bismuth oxide to provide radiopacity. Recently, another
      product, EndocemZr, which contains zirconium oxide (ZrO2) as a radiopacifier, was
      developed by the same company. In this study, the biological/odontogenic effects
      of EndocemZr were investigated in human primary dental pulp cells (hpDPCs) in
      vitro and on capped rat teeth in vivo. The biocompatibility of EndocemZr was
      similar to that of ProRoot and Endocem on the basis of cell viability tests and
      cell morphological analysis. The mineralization nodule formation, expression of
      odontogenic-related markers, and reparative dentin formation of EndocemZr group
      was similar to those of other material groups. Our results suggest that EndocemZr
      has the potential to be used as an effective material for vital pulp therapy,
      similar to ProRoot and Endocem. 

PMID- 25948142
TI  - Performance of dental impression materials: Benchmarking of materials and
      techniques by three-dimensional analysis.
AB  - Among other factors, the precision of dental impressions is an important and
      determining factor for the fit of dental restorations. The aim of this study was
      to examine the three-dimensional (3D) precision of gypsum dies made using a range
      of impression techniques and materials. Ten impressions of a steel canine were
      fabricated for each of the 24 material-method-combinations and poured with type 4
      die stone. The dies were optically digitized, aligned to the CAD model of the
      steel canine, and 3D differences were calculated. The results were statistically
      analyzed using one-way analysis of variance. Depending on material and impression
      technique, the mean values had a range between +10.9/-10.0 um (SD 2.8/2.3) and
      +16.5/-23.5 um (SD 11.8/18.8). Qualitative analysis using colorcoded graphs
      showed a characteristic location of deviations for different impression
      techniques. Three-dimensional analysis provided a comprehensive picture of the
      achievable precision. Processing aspects and impression technique were of
      significant influence. 

PMID- 25948143
TI  - In vitro microleakage of six different dental materials as intraorifice barriers
      in endodontically treated teeth.
AB  - The aim of this study was to compare the coronal sealing ability of six different
      dental materials: Three MTA-based cements and three established restorative
      materials by in vitro dye penetration method. For in vitro infiltration
      experiments, seventy extracted single-rooted human teeth were used. After crowns
      of teeth were reduced, root canals were prepared, and filled with gutta-percha
      cone. Teeth were randomly divided into 6 groups with 10 teeth per group. The
      orifice of each tooth was prepared to 3 mm depth and filled with the following
      materials: (I) ProRoot WMTA; (II) EndoCem Zr; (III) Angelus White; (IV) LuxaCore;
      (V) Fuji II LC; and (VI) Elite. After 5,000 cycles of thermocycling between 5
      degrees C and 55 degrees C, dye penetration of each specimen was measured. The
      order of less dye infiltration of coronal filling materials was: ProRoot
      WMTA<LuxaCore, Angelus White<EndoCem Zr<Fuji II LC<Elite (p<0.05). 

PMID- 25948144
TI  - Influences of archwire size and ligation method on the force magnitude delivered
      by nickel-titanium alloy archwires in a simulation of mandibular right lateral
      incisor linguoversion.
AB  - The present study investigated the influence of archwire size and ligation method
      on the force magnitude delivered by nickel-titanium alloy archwires to 4 incisor
      brackets (42, 41, 31, and 32) in a simulation of mandibular right lateral incisor
      linguoversion. The force delivered by 0.014 and 0.016 inch nickel-titanium alloy
      archwires was measured using a newly developed multi-sensor measuring system and
      the mean force magnitudes were compared between different archwire sizes when
      using conventional ligation (CL) with elastic modules or self-ligating (SL)
      brackets by three-way ANOVA and post-hoc Bonferroni's tests. The mean force
      magnitudes for the brackets were significantly decreased in the order of 42, 41,
      31, and 32 (p<0.01). The force magnitude was significantly larger in CL than SL
      at 42, 31, and 32 (p<0.05). In conclusion, the ligation method affected the force
      magnitude at 4 incisor brackets. Despite the ligation method, archwire size
      affected the force magnitude from 42 to 31. 

PMID- 25948145
TI  - Fabrication of bone cement that fully transforms to carbonate apatite.
AB  - The objective of this study was to fabricate a type of bone cement that could
      fully transform to carbonate apatite (CO3Ap) in physiological conditions. A
      combination of calcium carbonate (CaCO3) and dicalcium phosphate anhydrous was
      chosen as the powder phase and mixed with one of three kinds of sodium phosphate
      solutions: NaH2PO4, Na2HPO4, or Na3PO4. The cement that fully transformed to
      CO3Ap was fabricated using vaterite, instead of calcite, as a CaCO3 source. Their
      stability in aqueous solutions was different, regardless of the type of sodium
      phosphate solution. Rate of transformation to CO3Ap in descending order was
      Na3PO4>Na2HPO4>NaH2PO4. Transformation rate could be affected by the pH of
      solution. Results of this study showed that it was advantageous to use vaterite
      to fabricate CO3Ap-forming cement. 

PMID- 25948146
TI  - Effect of simplified ethanol-wet bonding on dentin bonding durability of etchand
      rinse adhesives.
AB  - This in vitro study evaluated the effects of simplified ethanol-wet bonding
      technique on dentin bonding durability of two etchand-rinse adhesives to bovine
      dentin. Sixteen freshly extracted bovine incisors were divided into four groups
      according to bonding technique (water-wet or ethanol-wet bonding) and adhesive
      (Single Bond 2 or Prime & Bond NT). After etching and rinsing, dentin surfaces
      were left either water-moist or immersed in ethanol. Following adhesive
      application and composite build-up, bonded teeth were sectioned into sticks for
      microtensile bond strength (uTBS) testing conducted after 24-h and 12-month water
      storage. There were no significant differences in bond strength among the groups
      at 24 h. At 12 months, the bond strengths of adhesives to dentin were
      significantly decreased (p<0.05). Simplified ethanol-wet bonding did not improve
      the resin-dentin bonding durability of tested etch-and-rinse adhesives. 

PMID- 25948147
TI  - Metallodithiolates as ligands in coordination, bioinorganic, and organometallic
      chemistry.

PMID- 25948148
TI  - Improving neonatal care in district and community health facilities in South
      Africa.
AB  - A high standard of newborn care, especially at a primary level, is needed to
      address the neonatal mortality rate in South Africa. The current approach to
      continuing training of health-care workers uses traditional methods of
      centralised teaching by formal tutors away from the place of work. This is no
      longer affordable, achievable or desirable, particularly in rural areas. An
      innovative system of self-directed learning by groups of nurses caring for
      mothers and their newborn infants uses specially prepared course books without
      the need for trainers. Using self-study supported by peer discussion groups,
      nurses can take responsibility for their own professional growth. This builds
      competence, confidence and a sense of pride. Since 1993, the Perinatal Education
      Programme has provided continuing learning opportunities for thousands of nurses
      in Southern Africa. A number of prospective trials have demonstrated that study
      groups can significantly improve knowledge and understanding, attitudes, clinical
      skills and quality of care provided to mothers and infants. A recent review of
      10,000 successful participants across a wide range of provinces, ages and home
      languages documented the success of the project. Using a question-and-answer
      format to promote problem-solving, case studies, simple skills workshops and
      multiple choice tests, each module addresses common conditions with appropriate
      care practices such as thorough drying at birth, delayed cord-clamping, skin-to
      skin care, breast feeding, basic resuscitation, correct use of oxygen therapy,
      hand-washing, blood glucose monitoring and promotion of parental bonding. The
      training material is now also available free of charge on an on-line website as
      well as being presented as e-books which can be downloaded onto personal
      computers, tablet readers and smart phones. This is supplemented by regular SMS
      text messages providing nurses with relevant 'knowledge bites'. All nurses caring
      for newborn infants now have easy, affordable access to continuing education
      which promises nationwide improvements in newborn care. 

PMID- 25948149
TI  - Acute phase treatment of VTE: Anticoagulation, including non-vitamin K antagonist
      oral anticoagulants.
AB  - The acute phase of venous thromboembolism (VTE) treatment focuses on the prompt
      and safe initiation of full-dose anticoagulation to decrease morbidity and
      mortality. Immediate management consists of resuscitation, supportive care, and
      thrombolysis for patients with haemodynamically significant pulmonary embolism
      (PE) or limb-threatening deep-vein thrombosis (DVT). Patients with
      contraindications to anticoagulants are considered for vena cava filters.
      Disposition for the acute treatment of VTE is then considered based on published
      risk scores and the patient's social status, as the first seven days carries the
      highest risk for VTE recurrence, extension and bleeding due to anticoagulation.
      Next, a review of: immediate and long-term bleeding risk, comorbidities (i. e.
      active cancer, renal failure, obesity, thrombophilia), medications, patient
      preference, VTE location and potential for pregnancy should be undertaken. This
      will help determine the most suitable anticoagulant for immediate treatment. The
      non-vitamin K antagonist oral anticoagulants (NOACs), including the factor Xa
      inhibitors apixaban, edoxaban and rivaroxaban as well as the direct-thrombin
      inhibitor dabigatran, are increasing the convenience of and options available for
      VTE treatment. Current options for immediate treatment include low-molecular
      weight heparin (LMWH), unfractionated heparin (UFH), fondaparinux, apixaban, or
      rivaroxaban. LMWH or UFH may be continued as monotherapy or transitioned to
      treatment with a VKA, dabigatran or edoxaban. This review describes the upfront
      treatment of VTE and the evolving role of NOACs in the contemporary management of
      VTE. 

PMID- 25948150
TI  - An evolutionary computing approach for parameter estimation investigation of a
      model for cholera.
AB  - We consider the problem of using time-series data to inform a corresponding
      deterministic model and introduce the concept of genetic algorithms (GA) as a
      tool for parameter estimation, providing instructions for an implementation of
      the method that does not require access to special toolboxes or software. We give
      as an example a model for cholera, a disease for which there is much mechanistic
      uncertainty in the literature. We use GA to find parameter sets using available
      time-series data from the introduction of cholera in Haiti and we discuss the
      value of comparing multiple parameter sets with similar performances in
      describing the data. 

PMID- 25948151
TI  - Taking high conservation value from forests to freshwaters.
AB  - The high conservation value (HCV) concept, originally developed by the Forest
      Stewardship Council, has been widely incorporated outside the forestry sector
      into companies' supply chain assessments and responsible purchasing policies,
      financial institutions' investment policies, and numerous voluntary commodity
      standards. Many, if not most, of these newer applications relate to production
      practices that are likely to affect freshwater systems directly or indirectly,
      yet there is little guidance as to whether or how HCV can be applied to water
      bodies. We focus this paper on commodity standards and begin by exploring how
      prominent standards currently address both HCVs and freshwaters. We then
      highlight freshwater features of high conservation importance and examine how
      well those features are captured by the existing HCV framework. We propose a new
      set of freshwater 'elements' for each of the six values and suggest an approach
      for identifying HCV Areas that takes out-of-fence line impacts into account,
      thereby spatially extending the scope of existing methods to define HCVs. We
      argue that virtually any non-marine HCV assessment, regardless of the production
      sector, should be expanded to include freshwater values, and we suggest how to
      put those recommendations into practice. 

PMID- 25948152
TI  - Tree Regeneration Under Different Land-Use Mosaics in the Brazilian Amazon's "Arc
      of Deforestation".
AB  - We studied the tree-regeneration patterns in three distinct agricultural
      settlements in the Eastern Amazon to test the influence of land-use mosaics. The
      following questions are addressed: are the floristic structure and composition of
      regenerating trees affected by the various land-use types applied in the
      agricultural settlements? Do tree-regeneration patterns respond similarly to
      distinct land-use mosaics? Is there a relationship between tree regeneration and
      soil characteristics among the land-use types? The regeneration was inventoried
      at 45 sampling points in each settlement. At each sampling point, fourteen soil
      variables were analyzed. Nine different land-use types were considered. The
      floristic structure and composition of the settlements showed differences in the
      density of individuals and species and high species heterogeneity among the land
      use types. The maximum Jaccard similarity coefficient found between land-use
      types was only 29%. Shade-tolerant species were the most diverse functional group
      in most land-use types, including pasture and annual crops, ranging from 91% of
      the number of species in the conserved and exploited forests of Travessao 338-S
      to 53% in the invaded pastures of Macaranduba. The land-use types influenced
      significantly the floristic structure and composition of regenerating trees in
      two agricultural settlements, but not in third the settlement, which had greater
      forest cover. This finding demonstrates that the composition of each land-use
      mosaic, established by different management approaches, affects regeneration
      patterns. Tree regeneration was related to soil characteristics in all mosaics.
      Preparation of the area by burning was most likely the determining factor in the
      differences in soil characteristics between forests and agricultural areas.

PMID- 25948153
TI  - Assessing the Role of Free-Roaming Horses in a Social-Ecological System.
AB  - Management actions concerning free-roaming horses attract controversy in many
      areas. In the Chilcotin region of British Columbia, Canada, social and cultural
      values influence debates about management of free-roaming horses and perceptions
      of their ecological impacts. A dearth of current, empirical research on the role
      and impacts of horses in local ecosystems results in management decisions being
      informed largely by studies from other ecoregions and locations, which may not
      accurately represent local ecological, social, cultural, and economic influences.
      We initiated the first socio-ecological study of horse sub-populations, their
      grazing habitat, and past management approaches affecting current conditions in
      the ?Elegesi Qayuse Wild Horse Preserve in Xeni Gwet'in (Tsilhqot'in) First
      Nations' territory. This exploratory study used mixed methods including a review
      of literature and unpublished data, assessment of vegetation in core grazing
      habitat, and exploration of local ecological and cultural knowledge and
      perceptions. Plant community composition and abundance in core grazing habitat of
      the Wild Horse Preserve are consistent with a structurally sound ecosystem. Socio
      cultural factors are important for managers to consider in effective decision
      making concerning horse populations. 

PMID- 25948154
TI  - Landscape Preferences, Amenity, and Bushfire Risk in New South Wales, Australia.
AB  - This paper examines landscape preferences of residents in amenity-rich bushfire
      prone landscapes in New South Wales, Australia. Insights are provided into
      vegetation preferences in areas where properties neighbor large areas of native
      vegetation, such as national parks, or exist within a matrix of cleared and
      vegetated private and public land. In such areas, managing fuel loads in the
      proximity of houses is likely to reduce the risk of house loss and damage.
      Preferences for vegetation appearance and structure were related to varying fuel
      loads, particularly the density of understorey vegetation and larger trees. The
      study adopted a qualitative visual research approach, which used ranking and
      photo-elicitation as part of a broader interview. A visual approach aids in
      focusing on outcomes of fuel management interventions, for example, by using the
      same photo scenes to firstly derive residents' perceptions of amenity and
      secondly, residents' perceptions of bushfire risk. The results are consistent
      with existing research on landscape preferences; residents tend to prefer
      relatively open woodland or forest landscapes with good visual and physical
      access but with elements that provoke their interest. Overall, residents'
      landscape preferences were found to be consistent with vegetation management that
      reduces bushfire risk to houses. The terms in which preferences were expressed
      provide scope for agency engagement with residents in order to facilitate
      management that meets amenity and hazard reduction goals on private land. 

PMID- 25948155
TI  - Enterprise-Level Motivations, Regulatory Pressures, and Corporate Environmental
      Management in Guangzhou, China.
AB  - This study examines the effects of internal motivations and external pressures on
      the integration of environmental management (EM) practices within manufacturing
      operations in China. The moderating role of perceptions toward the regulatory
      process is also considered along with comparisons between wholly Chinese-owned
      and foreign-owned enterprises. From a sample of 131 manufacturing companies in
      the Guangzhou area, it was found that the salience of fees and fines has a strong
      positive influence on perceptions toward the regulator (the local Environmental
      Protection Bureau, EPB). This also has a positive effect on perceptions toward
      regulations themselves for foreign-owned enterprises. Business-case motivations
      for EM positively shape enterprise perceptions toward regulations, whereas risk
      reduction motivations have a negative effect on perceptions toward regulations in
      foreign-owned enterprises. Enterprise perceptions toward the regulatory process
      have direct effects on the integration of EM practices in wholly Chinese-owned
      enterprises, but in opposite directions. While positive perceptions toward
      regulations have positive influence, positive perceptions toward regulators
      (i.e., the EPB) negatively affect it. Overall, these results indicated that
      promoting the adoption of EM practices depends on convincing business leaders
      that EM practices contribute to profit making. The regulatory process can
      potentially promote these practices, but measures need to be taken to ensure that
      the regulator is not co-opted by the regulated, especially in wholly Chinese
      owned enterprises. 

PMID- 25948156
TI  - Size/morphology induced tunable luminescence in upconversion crystals: ultra
      strong single-band emission and underlying mechanisms.
AB  - In this work, we present a two-step method to controllably synthesize novel and
      highly efficient upconversion materials, Lu5O4F7:Er(3+),Yb(3+) nano/micro
      crystals, and investigate their size/morphology induced tunable upconversion
      properties. In addition to the common phenomenon aroused by a surface quenching
      effect, direct experimental evidence for the regulation of phonon modes is
      obtained in nanoparticles. The findings in this work advance the existing
      mechanisms for the general explanation of size/morphology induced upconversion
      features. Because of the adjustment of phonon energy and density as well as the
      surface quenching effect, the biocompatible Lu5O4F7:Er(3+),Yb(3+) nanoparticles
      exhibit an ultra-strong single-band red upconversion, rendering them promising
      for biomedical applications. 

PMID- 25948158
TI  - A Simple and Reliable Method for Intracorporeal Circular-Stapled
      Esophagojejunostomy Using a Hand-Sewn Over-and-Over Suture Technique in
      Laparoscopic Total Gastrectomy.
AB  - BACKGROUND: The controversy regarding laparoscopic total gastrectomy (LTG) is
      mainly due to the difficulty associated with esophagojejunostomy during this
      procedure. Although several techniques have so far been reported to overcome this
      issue,1 (-) 4 a reliable technique has not yet been established. We developed
      intracorporeal esophagojejunostomy using a circular stapler in LTG with a hand
      sewn over-and-over suture technique, and have shown its favorable outcomes
      compared with those of conventional open surgery.5 This technique is presented in
      the video. METHODS: After transection of the esophagus, an over-and-over suture
      with a 2-0 monofilament is placed counterclockwise from the right to the left
      side of the cut end in an outside-to-inside direction, and then from the left to
      the right side in an inside-to-outside direction. After insertion of the anvil
      head into the esophagus, it was fixed by ligation of the thread. Finally,
      intracorporeal esophagojejunal anastomosis was performed using a circular
      stapler. RESULTS: In LTG, reconstruction using this method was performed for 23
      consecutive patients with gastric cancer. There were no serious intraoperative
      complications or need for conversion to open surgery. Anastomotic leakage and
      stenosis occurred in one case each, respectively. The mean time for fixation of
      the anvil to the esophagus was 15 min for the last 12 consecutive patients.
      CONCLUSIONS: This method is simple and feasible, and the advantage of this
      technique is the elimination of the backhand stroke throughout the suturing
      procedure.

PMID- 25948157
TI  - The negative feedback regulation of microRNA-146a in human periodontal ligament
      cells after Porphyromonas gingivalis lipopolysaccharide stimulation.
AB  - OBJECTIVE: Toll-like receptors (TLRs) pathway has been demonstrated to play an
      important role in periodontitis. However, the regulatory mechanism of microRNAs
      (miRNAs) on TLRs pathway is still unclear. Hence, this study is to explore the
      function of miRNA-146a in inflammatory reaction induced by Porphyromonas
      gingivalis lipopolysaccharide (LPS) in human periodontal ligament cells (hPDLCs).
      METHODS: Cells were treated with 1 or 10 MUg/ml P. gingivalis LPS. The expression
      of TLR2, TLR4 and miRNA-146a were measured by real-time polymerase chain reaction
      (PCR). Enzyme-linked immunosorbent assay (ELISA) was applied to detect nuclear
      factor (NF)-kappa B p65 nuclear activity, interleukin-1beta (IL-1beta), IL-6, IL
      8 and tumor necrosis factor-alpha (TNF-alpha). To examine the underlying
      mechanisms, cells were exposed to anti-TLR2/4 mAb or miRNA-146a inhibitor/mimic
      and evaluated by real-time PCR and ELISA. RESULTS: 10 MUg/ml P. gingivalis LPS
      increased the expressions of TLR2 (3.79 +/- 0.31), TLR4 (2.21 +/- 0.31), and
      miRNA-146a (4.91 +/- 0.87), NF-kappa B p65 nuclear activity (6.51 +/- 0.77 fold)
      (p < 0.05). 1 MUg/ml P. gingivalis LPS induced TLR2 (3.05 +/- 0.23), miRNA-146a
      (3.66 +/- 0.83) and NF-kappa B p65 nuclear activity (4.06 +/- 0.78 fold) (p <
      0.05), except TLR4 (1.11 +/- 0.30, p > 0.05). Also, cytokines production
      increased (p < 0.05). The up-regulation of miRNA-146a could be blocked by anti
      TLR2/4 mAb (p < 0.05). After the blockage of miRNA-146a, TLR2, TLR4, NF-kappa B
      p65 nuclear activity and proinflammatory cytokines increased. However, after
      application of miRNA-146a mimic, the levels of these indexes decreased obviously
      (p < 0.05). CONCLUSION: MiRNA-146a functions as a negative feedback regulator via
      down-regulating proinflammatory cytokine secretion and blocking TLRs signaling
      pathway in hPDLCs after P. gingivalis LPS stimulation.

PMID- 25948159
TI  - Histologic and Immunohistochemical Alterations Associated with Cytoreductive
      Surgery and Heated Intraperitoneal Chemotherapy.
AB  - BACKGROUND: Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy
      (HIPEC) are used to treat peritoneal carcinomatosis from a variety of primary
      tumor sites. Little is known about the in vivo effects of CRS and HIPEC. METHODS:
      We examined tumor and non-neoplastic peritoneal tissue samples from 38 patients
      undergoing CRS and HIPEC for appendiceal or colorectal carcinomatosis, using
      conventional histologic analysis and immunohistochemical analysis for markers of
      early DNA damage (phosphorylated H2AX, gammaH2AX) and early necrosis
      (extracellular HMGB1). Findings were correlated with clinicopathologic features
      and oncologic outcome. RESULTS: Histologic findings corresponding with CRS and
      HIPEC included extensive submesothelial inflammatory infiltrate, endothelial
      activation, mesothelial karyolysis and surface fibrin deposition. Endothelial
      activation in submesothelial vessels exhibited high specificity for samples
      obtained following HIPEC relative to samples obtained following CRS but prior to
      HIPEC. Mesothelial nuclear gammaH2AX staining and submesothelial extracellular
      HMGB1 staining increased progressively following CRS and HIPEC, consistent with
      DNA damage and necrosis. No significant increase in tumor staining for markers
      was seen with CRS or HIPEC. Submesothelial HMGB1 staining was associated with
      increased progression-free survival on univariate analysis. CONCLUSIONS: The
      immediate histologic effects of CRS and HIPEC are defined and provide evidence
      that DNA damage and early steps of necrosis are underway in mesothelial tissues
      at the conclusion of the procedure. Further research will be necessary to
      investigate the impact of these findings on long-term oncologic outcome, and may
      provide insight into the downstream effects of CRS and HIPEC that could
      facilitate refinement of regional therapeutic regimens for carcinomatosis.

PMID- 25948160
TI  - Semi-automated echocardiographic quantification of right ventricular size and
      function.
AB  - Although parameters of right ventricular (RV) size and function are clinically
      important, echocardiographic assessment of this chamber is complex. Existing
      quantitative approaches rely on manual measurements performed on different
      images, and are thus time-consuming. Consequently, in clinical practice,
      qualitative assessment is usually used instead. We tested a new approach for
      automated measurements of RV size and function using speckle tracking by
      comparing them to the conventional manual methodology. Transthoracic images were
      obtained in 149 patients with a wide range of RV size and function, and were
      analyzed by an expert using conventional techniques to obtain RV end-diastolic
      and end-systolic areas, fractional area change, dimensions (basal and mid-cavity
      diameters and length), tricuspid annular plane systolic excursion and peak
      systolic velocity. Same parameters were obtained using the semi-automated
      software (Epsilon Imaging), which requires tracing of the RV endocardial boundary
      in a single frame in the RV focused view. Fifteen patients were excluded due to
      image quality (90% feasibility). Time required for the automated analysis was
      approximately 30 s per patient, compared to 4 min for conventional analysis. The
      parameters obtained with the semi-automated approach were in good agreement with
      manual measurements: r-values 0.79-0.95 for RV size and 0.70-0.74 for function
      indices and biases of 2-22% of the mean measured values, which were comparable to
      the intrinsic variability of the conventional technique. In conclusion, the semi
      automated technique is feasible, fast and provides quantitative parameters of RV
      size and function, which are comparable to conventional measurements.

PMID- 25948161
TI  - Leishmania donovani P23 protects parasites against HSP90 inhibitor-mediated
      growth arrest.
AB  - In Leishmania donovani, the HSP90 chaperone complex plays an essential role in
      the control of the parasite's life cycle, general viability and infectivity.
      Several of the associated co-chaperones were also shown to be essential for
      viability and/or infectivity to mammalian cells. Here, we identify and describe
      the co-chaperone P23 and distinguish its function from that of the structurally
      related small heat shock protein HSP23. P23 is expressed constitutively and
      associates itself with members of the HSP90 complex, i.e. HSP90 and Sti1. Viable
      P23 gene replacement mutants could be raised and confirmed as null mutants
      without deleterious effects on viability under a variety of physiological growth
      conditions. The null mutant also displays near-wild-type infectivity, arguing
      against a decisive role played by P23 in laboratory settings. However, the P23
      null mutant displays a marked hypersensitivity against HSP90 inhibitors
      geldanamycin and radicicol. P23 also appears to affect the radicicol resistance
      of a HSP90 Leu33-Ile mutant described previously. Therefore, the annotation of L.
      donovani P23 as HSP90-interacting co-chaperone is confirmed. 

PMID- 25948162
TI  - Safety of long-term dietary supplementation with L-arginine in rats.
AB  - This study was conducted with rats to determine the safety of long-term dietary
      supplementation with L-arginine. Beginning at 6 weeks of age, male and female
      rats were fed a casein-based semi-purified diet containing 0.61 % L-arginine and
      received drinking water containing L-arginine-HCl (0, 1.8, or 3.6 g L-arginine/kg
      body-weight/day; n = 10/group). These supplemental doses of L-arginine were
      equivalent to 0, 286, and 573 mg L-arginine/kg body-weight/day, respectively, in
      humans. After a 13-week supplementation period, blood samples were obtained from
      rats for biochemical analyses. Supplementation with L-arginine increased plasma
      concentrations of arginine, ornithine, proline, homoarginine, urea, and nitric
      oxide metabolites without affecting those for lysine, histidine, or
      methylarginines, while reducing plasma concentrations of ammonia, glutamine, free
      fatty acids, and triglycerides. L-Arginine supplementation enhanced protein gain
      and reduced white-fat deposition in the body. Based on general appearance,
      feeding behavior, and physiological parameters, all animals showed good health
      during the entire experimental period; Plasma concentrations of all measured
      hormones (except leptin) did not differ between control and arginine-supplemented
      rats. L-Arginine supplementation reduced plasma levels of leptin. Additionally, L
      arginine supplementation increased L-arginine:glycine amidinotransferase activity
      in kidneys but not in the liver or small intestine, suggesting tissue-specific
      regulation of enzyme expression by L-arginine. Collectively, these results
      indicate that dietary supplementation with L-arginine (e.g., 3.6 g/kg body
      weight/day) is safe in rats for at least 91 days. This dose is equivalent to 40 g
      L-arginine/kg body-weight/day for a 70-kg person. Our findings help guide
      clinical studies to determine the safety of long-term oral administration of L
      arginine to humans.

PMID- 25948163
TI  - L-Glycyl-L-glutamine provides the isolated and perfused young and middle-aged rat
      heart protection against ischaemia-reperfusion injury.
AB  - The amino acids glycine and glutamine have been implicated in myocardial
      protection of the much studied young adult heart. This study aimed to determine
      whether such protection could be enhanced using the dipeptide, L-glycyl-L
      glutamine (gly-gln) in both young hearts and in middle-aged hearts representative
      of a more clinically relevant age group. Hearts from 8-week-old and 36-week-old
      rats were perfused in the Langendorff mode for 20 min, before 40 min global
      normothermic ischaemia and 30 min reperfusion. Where present, 0.5, 2, or 5 mM gly
      gln was added 10 min into baseline perfusion, was present throughout ischaemia
      and was washed out after 10 min reperfusion. Reperfusion damage was assessed from
      the release of lactate dehydrogenase. Metabolic fitness was assessed from the
      time to ischaemic contracture and the accumulation of lactate and thiobarbituric
      acid reactive substances during ischaemia. The presence of 5 mM gly-gln
      significantly improved the post-ischaemic rate pressure product (RPP) and
      decreased reperfusion damage in both the 8 (RPP in control on reperfusion 5527 +/
      957 vs. 10,320 +/- 795 mmHg beat min(-1) in 5 mM gly-gln, n = 6 +/- SE, p <
      0.05) and 36-week-old (RPP in control on reperfusion 1964.33 +/- 876.3 vs. 4008
      +/- 675 mmHg beat min(-1), n = 6 +/- SE, p < 0.01) hearts. Five mM gly-gln also
      increased the time to ischaemic contracture and was able to protect against the
      rise in lactate that occurred in the controls during ischaemia. These results
      suggest that gly-gln has good potential as a combatant against ischaemia
      reperfusion injury in both the young adult and middle-aged populations.

PMID- 25948164
TI  - Nasal nitric oxide in sleep-disordered breathing in children.
AB  - BACKGROUND: Inflammation plays a role in the pathogenesis and consequences of
      sleep-disordered breathing (SDB). The nasal mucosa and paranasal sinuses produce
      high levels of nitric oxide (NO). In asthma, exhaled NO is a marker of airway
      inflammation. There is only limited information whether nasal NO (nNO)
      accompanies also chronic upper airway obstruction, specifically, SDB. The
      objective of this study was to investigate nNO levels in children with SDB in
      comparison to healthy non-snoring children. METHODS: Nasal NO was measured in
      children who underwent overnight polysomnographic studies due to habitual snoring
      and suspected SDB and in healthy non-snoring controls. RESULTS: One hundred and
      eleven children participated in the study: 28 with obstructive sleep apnea (OSA),
      60 with primary snoring (PS), and 23 controls. Nasal NO levels were significantly
      higher in children with OSA and PS compared to controls (867.4 +/- 371.5, 902.0
      +/- 330.9, 644.1 +/- 166.5 ppb, respectively, p = 0.047). No difference was
      observed between children with OSA and PS. No correlations were found between nNO
      levels and any of the PSG variables, nor with age, BMI percentile or tonsils
      size. CONCLUSIONS: Compared to healthy controls, nNO is increased in children
      with SDB, but it is not correlated with disease severity. This is probably due to
      the local mechanical processes and snoring.

PMID- 25948165
TI  - The electronic origin of shear-induced direct to indirect gap transition and
      anisotropy diminution in phosphorene.
AB  - Artificial monolayer black phosphorus, so-called phosphorene, has attracted
      global interest with its distinguished anisotropic, optoelectronic, and
      electronic properties. Here, we unraveled the shear-induced direct-to-indirect
      gap transition and anisotropy diminution in phosphorene based on first-principles
      calculations. Lattice dynamic analysis demonstrates that phosphorene can sustain
      up to 10% applied shear strain. The bandgap of phosphorene experiences a direct
      to- indirect transition when 5% shear strain is applied. The electronic origin of
      the direct-to-indirect gap transition from 1.54 eV at ambient conditions to 1.22
      eV at 10% shear strain for phosphorene is explored. In addition, the anisotropy
      diminution in phosphorene is discussed by calculating the maximum sound
      velocities, effective mass, and decomposed charge density, which signals the
      undesired shear-induced direct-to-indirect gap transition in applications of
      phosphorene for electronics and optoelectronics. On the other hand, the shear
      induced electronic anisotropy properties suggest that phosphorene can be applied
      as the switcher in nanoelectronic applications. 

PMID- 25948167
TI  - Biochemical composition of the fluid of ovarian cysts and pre-ovulatory follicles
      compared to the serum in sows.
AB  - OBJECTIVE: The objective of this study was to compare the biochemical composition
      of follicular cysts, pre-ovulatory follicles and serum in sows. MATERIAL AND
      METHODS: The research involved multiparous sows (cysts-bearing sows, n = 21; non
      cysts-bearing sows, n = 22). Concentration of glucose, protein, cholesterol
      (CHOL), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and
      triacylglycerol (TAG) in the samples was determined. RESULTS: Glucose
      concentration in serum was higher than in cysts and follicles (p < 0.01) and
      glucose concentration in cysts was higher than in follicles (p < 0.01).
      Differences were also observed between the concentration of glucose in serum of
      cysts-bearing and non-cysts-bearing sows (p < 0.01). Protein concentration in
      cysts and follicles was lower than in serum (p < 0.01). Concentration of
      cholesterol in the serum of cysts-bearing sows and non-cysts-bearing sows was
      higher than the one in cysts and follicles (p < 0.01). Cholesterol concentration
      in the serum of cysts-bearing sows was higher than the one in non-cysts-bearing
      sows (p < 0.01). Concentration of HDL in serum of both cysts-bearing and non
      cysts-bearing sows was also higher than the one in cysts and follicles (p <
      0.01). Cysts-bearing sows had a higher concentration of HDL in the serum than non
      cysts-bearing sows. Differences were also observed between the concentration of
      HDL in cysts and the one in follicles (p < 0.05). LDL was determined not to be
      present in either cysts or pre-ovulatory follicles. TAG concentration in the
      serum of cysts-bearing sows was higher than the one in the serum of non-cysts
      bearing sows (p < 0.05). Differences were also detected between the TAG
      concentrations in cysts and in follicles (p < 0.01). CONCLUSION: The differences
      in the biochemical composition of the fluid in follicular cysts and pre-ovulatory
      follicles point to the variable intensification of the course of metabolic
      processes in pathological and physiological ovarian structures.

PMID- 25948166
TI  - Analgesia and respiratory function after laparoscopic cholecystectomy in patients
      receiving ultrasound-guided bilateral oblique subcostal transversus abdominis
      plane block: a randomized double-blind study.
AB  - BACKGROUND: Transversus abdominis plane (TAP) block has been shown to ameliorate
      postoperative pain after abdominal surgery. Postoperative pain-associated
      respiratory compromise has been the subject of several studies. Herein, we
      evaluate the effect of oblique subcostal TAP (OSTAP) block on postoperative pain
      and respiratory functions during the first 24 postoperative hours.
      MATERIAL/METHODS: In this double-blind, randomized study, 76 patients undergoing
      laparoscopic cholecystectomy were assigned to either the OSTAP group (n=38) or
      control group (n=38). Bilateral ultrasound-guided OSTAP blocks were performed
      with 20 ml 0.25% bupivacaine after induction of general anesthesia. Both the
      OSTAP and control groups were treated with paracetamol, tenoxicam, and tramadol
      as required for postoperative analgesia. Visual Analog Scale (VAS) pain scores
      (while moving and at rest), forced expiratory volume in the first second (FEV1),
      forced vital capacity (FVC), peak expiratory flow rate (PEFR), arterial blood gas
      variables, and opioid consumption were assessed during first 24 h. RESULTS: VAS
      pain scores at rest and while moving were significantly lower in the OSTAP group
      on arrival to PACU and at 2 h postoperatively. The total postoperative tramadol
      requirement was significantly reduced at 0-2 h and 2-24 h in the OSTAP group.
      Postoperative deterioration in FEV1 and FVC was significantly less in the OSTAP
      group when compared to the control group (P<0.01 and P<0.05, respectively). There
      were no between-group differences in arterial blood gas variables. CONCLUSIONS:
      After laparoscopic cholecystectomy, OSTAP block can provide significant
      improvement in respiratory function and better pain relief with lower opioid
      requirement.

PMID- 25948168
TI  - Temperature-Responsive Poly(N-isopropylacrylamide) Modified Gold Nanoparticle
      Protein Conjugates for Bioactivity Modulation.
AB  - It is important to effectively maintain and modulate the bioactivity of protein
      nanoparticle conjugates for their further and intensive applications. The
      strategies of controlling protein activity via "tailor-made surfaces" still have
      some limitations, such as the difficulties in further modulation of the
      bioactivity and the proteolysis by some proteases. Thus, it is essential to
      establish a responsive protein-nanoparticle conjugate system to realize not only
      controllable modulations of protein activity in the conjugates by incorporating
      sensitivity to environmental cues but also high resistance to proteases. In the
      work reported here, Escherichia coli (E. coli) inorganic pyrophosphatase (PPase)
      and poly(N-isopropylacrylamide) (pNIPAM) were both fabricated onto gold
      nanoparticles (AuNPs), forming AuNP-PPase-pNIPAM conjugates. The bioactivity
      modulating capability of the conjugates with changes in temperature was
      systematically investigated by varying the molecular weight of pNIPAM, the
      PPase/pNIPAM molar ratio on AuNP, and the orientation of the proteins. Under
      proper conditions, the activity of the conjugate at 45  degrees C was
      approximately 270% of that at 25  degrees C. In the presence of trypsin
      digestion, much less conjugate activity than protein activity was lost. These
      findings indicate that the fabrication of AuNP-protein-pNIPAM conjugates can both
      modulate protein activity on a large scale and show much higher resistance to
      protease digestion, exhibiting great potential in targeted delivery, controllable
      biocatalysis, and molecular/cellular recognition. 

PMID- 25948169
TI  - Each GPI-anchored protein species forms a specific lipid raft depending on its
      GPI attachment signal.
AB  - We previously reported a method, termed enzyme-mediated activation of radical
      sources (EMARS) for analysis of co-clustered molecules with horseradish
      peroxidase (HRP) fusion proteins expressed in living cells. This method is
      featured by radical formation of labeling reagents by HRP. In the current study,
      we have employed another labeling reagent, fluorescein-conjugated tyramide (FT)
      instead of the original arylazide compounds. Although hydrogen peroxide is
      required for the activation of FT, the labeling efficiency by HRP and the
      nonspecific reactions by endogenous enzyme(s) have been dramatically improved
      compared with the original fluorescein arylazide. This revised EMARS method has
      enabled visualization of co-clustered molecules in the endoplasmic reticulum and
      Golgi membranes with confocal microscopy. By using this method, we have found
      that GPI-anchored proteins, decay accelerating factor (DAF) and Thy-1 are
      exclusively co-clustered with HRP-DAFGPI and HRP-Thy1GPI, in which GPI attachment
      signals of DAF and Thy-1 have been connected to HRP, respectively. Furthermore,
      the N-glycosylation types of DAF and Thy-1 have been found to correspond to those
      of HRP-DAFGPI and HRP-Thy1GPI, respectively. These results indicate that each GPI
      anchored protein species forms a specific lipid raft depending on its GPI
      attachment signal, and that the EMARS method can segregate individual lipid
      rafts.

PMID- 25948170
TI  - The utilization of incinerated hip and knee prostheses for identification.
AB  - PURPOSE: The aim of this study was to test various methods of retrieving number
      data from hip and knee implants from cremated human remains and to validate our
      findings by cross referencing our results with the national joint replacement
      registry. METHOD: Implants were collected from the remains of individuals who had
      donated their bodies to science following routine planned cremation. A number of
      different chemical and physical methods to expose the implant numbers on cremated
      implants to the point that they were legible were tested. The retrieved data on
      the implants was referred to the Australian Orthopaedic Association National
      Joint Replacement Registry to identify the individuals, and the names were cross
      referenced from the original list of donors. RESULTS: It was possible to retrieve
      sufficient data from cremated implants to track the name of the recipient of
      implants if they were placed following the formation of the registry. Both wet
      and dry paper (1200 size and without moisture), and fine grade steel wool (used
      in antique restoration), were successful in removing the oxidized layer from
      implants. With hip implants, it was discovered that the best area to retrieve
      clear readable information is inside the ball head or at the end of the neck as
      this area is protected from oxidation during incineration. CONCLUSION:
      Incinerated or cremated hip and knee implants may be used to assist in the
      identification of a decedent following careful treatment, in conjunction with
      national joint revision registries and company data.

PMID- 25948172
TI  - Influence of the synergistic effect between Co-N-C and ceria on the catalytic
      performance for selective oxidation of ethylbenzene.
AB  - A series of catalysts, i.e. metal oxides (MO) such as CeO2, Fe2O3 and Al2O3
      supported Co-N-C (Co-N-C/MO) were prepared by heating supported cobalt porphyrin
      in a N2 atmosphere. Among the Co-N-C/MO catalysts, Co-N-C/CeO2 shows a remarkable
      catalytic performance for ethylbenzene oxidation with ethylbenzene conversion of
      33.1% and selectivity to acetophenone of 74.8%. In addition, the interaction
      between Co-N-C and supports was tentatively characterized by techniques such as
      XRD, HRTEM, XPS etc. According to XPS, the presence of the redox cycle between
      Ce(3+) and Ce(4+) in CeO2 facilitates the formation of cobalt ions in the high
      valence state and the Co-Nx sites, which are typically responsible for the high
      catalytic activity. The high performance benefits from the synergistic effect
      between Co-N-C and CeO2 and the well-dispersed Co-based sites. 

PMID- 25948173
TI  - Electronic modulation of infrared radiation in graphene plasmonic resonators.
AB  - All matter at finite temperatures emits electromagnetic radiation due to the
      thermally induced motion of particles and quasiparticles. Dynamic control of this
      radiation could enable the design of novel infrared sources; however, the
      spectral characteristics of the radiated power are dictated by the
      electromagnetic energy density and emissivity, which are ordinarily fixed
      properties of the material and temperature. Here we experimentally demonstrate
      tunable electronic control of blackbody emission from graphene plasmonic
      resonators on a silicon nitride substrate. It is shown that the graphene
      resonators produce antenna-coupled blackbody radiation, which manifests as narrow
      spectral emission peaks in the mid-infrared. By continuously varying the
      nanoresonator carrier density, the frequency and intensity of these spectral
      features can be modulated via an electrostatic gate. This work opens the door for
      future devices that may control blackbody radiation at timescales beyond the
      limits of conventional thermo-optic modulation. 

PMID- 25948171
TI  - Advances in CNS Imaging Agents: Focus on PET and SPECT Tracers in Experimental
      and Clinical Use.
AB  - The physiological functioning of the brain is not well-known in current day
      medicine and the pathologies of many neuropsychiatric disorders are still not yet
      fully understood. With our aging population and better life expectancies, it has
      become imperative to find better biomarkers for disease progression as well as
      receptor target engagements. In the last decade, these major advances in the
      field of molecular CNS imaging have been made available with tools such as
      functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy
      (MRS), single photon emission computed tomography (SPECT), and neuroreceptor
      targeted positron emission tomography (PET). These tools have given researchers,
      pharmaceutical companies, and clinical physicians a better method of
      understanding CNS dysfunctions, and the ability to employ improved therapeutic
      agents. This review is intended to provide an update on brain imaging agents that
      are currently used in clinical and translational research toward treatment of CNS
      disorders. The review begins with amyloid and tau imaging, the former of which
      has at least three [(18)F] agents that have been recently approved and will soon
      be available for clinical use for specific indications in the USA and elsewhere.
      Other prevalent PET and SPECT neurotransmitter system agents, including those
      newly US FDA-approved imaging agents related to the dopaminergic system, are
      included. A review of both mature and potentially growing PET imaging agents,
      including those targeting serotonin and opiate receptor systems, is also
      provided.

PMID- 25948174
TI  - [Copy number variations in pediatric acute myeloid leukemia].
AB  - OBJECTIVE: To evaluate the copy number variations (CNV) of gene in pediatric
      acute myeloid leukemia (AML) and its correlation with clinical features and
      prognosis. METHODS: The clinical data of 130 children aged <14 years with newly
      diagnosed AML from May 2006 to March 2013 were analyzed restrospectively. The CNV
      were analyzed by multiplex ligation-dependent probe amplification (MLPA). Thirty
      eight normal children were selected in control group. All the data were
      statistically analyzed using SPSS16.0 software. RESULTS: gene CNV of
      2p24.3(MYCN), 10q23(PTEN) and 13q14(RB1, MIR15A, DLEU) were detected in more than
      10% of the patients. CNV were detected in 49 cases(37.7%). The median loss and
      gain CNV frequencies per sample were 4. The CNV of TP53 correlated significantly
      with relapse. The loss ond gain CNV have no influence to EFS, DSF and OS. CNV
      were detected in the twelve percent of patients, but they were not detected with
      routine karyotype method. CONCLUSION: The MLPA technique combined with
      karyotyping makes a substantial increase in the diagnostic rate. Patients with
      TP53 alterations have significantly higher relapse rate.

PMID- 25948175
TI  - [Characteristics of karyotypes and gene mutations for elder acute myeloid
      leukemia].
AB  - OBJECTIVE: To investigate the incidence of karyotypes and gene mutations for
      elder acute myeloid leukemia and to explore the relationship between each other.
      METHODS: Clinical data and bone marrow samples of elder AML patients were
      collected. Karyotype and gene mutation (FLT3, NPM1, C-Kit, CEBPalpha, DNMT3A)
      test were performed, characteristics of karyotypes and gene mutations were
      analysed. RESULTS: The incidence of better risk karyotype was 16.6%, in which the
      incidences of t(15;17), t(8;21) and inv (16)/t(16;16) were 3.90%, 10.73%, and
      1.95% respectively; the incidence of intermediate risk karyotype was 72.2%, in
      which the incidence of normal karyotype was 57.86%; the incidence of poor risk
      karyotype was 11.20%, in which the incidence of of MLL/11q23, complex karyotype
      and monosomal karyotype were 1.95%, 6.34%, 5.85% respectively; the incidences of
      FLT3, NPM1, C-Kit, CEBPalpha, DNMT3A mutation were 12.57%, 22.06%, 2.16%, 14.71%,
      15.71% respectively. Compared with patients older than 60 years, patients with
      age of 55-60 years were with less complex karyotype (1.09% vs 10.62%)(P=0.003)
      and monosomal karyotype (2.17% vs 8.85%)(P=0.032), and more t(8;21)(17.39% vs
      5.31%)(P=0.008) and inv (16)/t(16;16)(4.35% vs 0.00%)(P=0.045). CONCLUSION: For
      older AML patients, great difference in the distribution of karyotyes was found
      between the patients older than 60 years and patients with age of 55-60 years,
      while no such characteristics was found for gene mutations. Good elucidation of
      karyotypes and gene mutations are key for the treatment of older acute myeloid
      leukemia patients.

PMID- 25948176
TI  - [Macrophage inflammatory protein-1alpha promotes the growth of acute myeloid
      leukemia cells].
AB  - BACKGROWND: Macrophage inflammatory protein-1alpha (MIP-l alpha/CCL3) belongs to
      the C-C chemokine family (CCL3), which can be secreted by macrophages, other
      types of hematopoietic cells and bone marrow stromal cells. Higher levels of MIP
      1alpha were found to be associated with several kinds of hematologic
      malignancies, including multiple myeloma (MM), chronic lymphocytic leukemia (CLL)
      and chronic myeloid leukemia (CML). Moreover, MIP-1alpha has been reported to be
      an adverse prognostic factor for CLL. However, the impact of MIP-1alpha on acute
      myeloid leukemia (AML) has been poorly investigated. OBJECTIVE: To investigate
      the influence of MIP-1alpha on proliferction of AML cells. METHODS: Using MLL-AF9
      induced AML mouse model, the expression of MIP-1alpha was measured by real time
      quantitative RT-PCR. AML cell proliferation was examined by cell counting and
      colony forming assay (CFC). The influence of blocking the MIP-1alpha action on
      the growth and pathogenic ability of AML cells was explored by using the small
      molecule antagonist for interfering interaction of MIP-1alpha with its receptor
      CCR1. RESULTS: The MIP-1alpha could promote the proliferation and colony
      formation of AML cells, the blocking MIP-1a could inhibit the growth of AML cells
      and delay onset of AML. CONCLUSION: The MIP-1a promotes the occurence and
      progression of AML, therefore blocking the MIP-1alpha signal pathway may be
      served as a strategy to inhibit the growth of AML cells, and MIP-1alpha can be a
      potential target for treatment of AML.

PMID- 25948177
TI  - [Cytogenetic characteristics of 163 children with acute lymphoblastic leukemia].
AB  - OBJECTIVE: To further understand the cytogenetic characteristics of pediatric
      acute lymphoblastic leukemia (ALL). METHODS: Cytogenetic abnormalities of 163
      children with newly diagnosed ALL (0-17 years of age) were evaluated by
      conventional cytogenetic analysis and fluorescent in situ hybridization findings.
      RESULTS: Chromosome abnormalities were detected in 87.7% of patients (143/163).
      The ploidy levels most frequently observed among ALL patients were high
      hyperdiploidy (51-67 chromosomes) (45 cases, 27.6%), Chromosomes X and 21 were
      gained in 100% of these cases. The most common genetic alterations were
      t(12;21)/ETV6/RUNX1 (26 cases, 16.0%), followed by t(1;19)/TCF3/PBX1 (13
      patients, 8.0%), t(4;11)/MLL rearrangement and t(8;14) IGH/MYC (6 cases, 3.7%),
      t(9;22)/BCR/ABL(2 cases, 1.2%), and iAMP21 (1 patient, 0.6%). The no-classical
      structural abnormalities included dup(1q) in 20.2%, del(6q) and del(9p) in 10.4%,
      del(12p) in 12.9% and del(13q) in 5.5%. The incidences of t(12;21), t(1;19),
      t(9;22) and high hyperdiploidy were consistent with reports in Western children
      (P>0.25). The incidence of (9;22) seemed to be much lower in our study than that
      in Korea (1.5% vs 9.5%, P<0.005). CONCLUSION: Cytogenetic findings of childhood
      ALL patients are similar to that of Western countries, it seems no more adverse
      risk factors.

PMID- 25948178
TI  - [Expression of Ki-67 in chronic lymphocytic leukemia and its clinical
      significance].
AB  - OBJECTIVE: To investigate the expression of nuclear antigen Ki-67 in CLL patients
      and realationship of Ki-67 expression with other clinical parameters. METHODS:
      Twenty-Six confirmed cases of CLL were analysised retrospectively. The
      immhnohistochemical method was carried out to examine the expression of Ki-67 in
      bone marrow cells, the flow cytometer was used to detect ZAP70 (Zeta chain
      associated protein), CD38 and other markers, additionally, a panel of probes RB1
      (13q14), ATM (11q22.3), P53 (17p13.1) and CSP12 (+12) FISH were perfomed to
      detect the cytogenetic abnormalities. RESULTS: Out of 26 patients, 15 cases
      (57.7%) showed positive expression of Ki-67, 11 cases (42.3%) showed negative
      expression of Ki-67, the average rate of Ki-67 positive expression was (10.86+/
      7.36)%. The level of Ki-67 did not relate with sex, age, Hb, platelet, ZAP70,
      ATM. beta2-MG, IgHV and P53, but related to the Rai staging (P=0.01, r=0.517),
      CD38 (P=0.02, r=0.469), 13q14 (P=0.021, r=-0.48), and there was statistically
      significant difference (P<0.05). CONCLUSION: The Ki-67 level is higher in
      progressive stage of CLL and the Ki-67 expression is related with Rai staging,
      CD38, 13q14. The expression level of Ki-67 may be used as indicator for
      evaluation of CLL prognosis and guiding treatment for this disease.

PMID- 25948179
TI  - [FLT3 Gene Mutations in Acute Myeloid Leukemia].
AB  - OBJECTIVE: This study was aimed to detect the FLT3 gene mutation in patients with
      de-novo acute myeloid leukemia (AML), and to investigate its prognostic value and
      clinical significance. METHODS: Polymerase chain reaction (PCR) was used to
      detect FLT3 gene mutation, in bone marrow samples of 54 patients with de novo
      AML. RESULTS: The incidence of FLT3-ITD mutation in 54 de-novo AML patients was
      22.22%, 10 out of 12(83.3%) AML patients were identified with normal karyotype,
      while 16.7% patients were identified as with abnormal karyotype. The peripheral
      blood white cell count and bone marrow blast cells were significantly higher in
      the patients with FLT3-ITD mutation than those in patients without FLT3-ITD
      mutation (P<0.05), but there was no statistically significant difference in sex,
      age, CR rate of the first course induction chemotherapy, survival rate and so on
      between the two groups. Two cases had FLT3-TKD gene mutation; as compared with
      FLT3-TKD negative AML patients there was no statistical difference in sex, age,
      white blood cell count, the percentage of marrow blasts and CR rate of the first
      course of treatment at the initial diagnosis. CONCLUSION: FLT3-ITD mutation
      positive likely occurs in AML patients with normal karyotype, the FLT3-ITD
      mutation is associated with higher peripheral white cell count and higher
      percentage of bone marrow blast cells.

PMID- 25948180
TI  - [Comparison of the Tumor-forming Rate between the SCID and NOD/SCID Mice used to
      Set up Acute Myeloid Leukemia Model].
AB  - OBJECTIVE: To compare the tumor-forming rate between the SCID and NOD/SCID mice
      to set up acute myeloid leukemia (AML) mouse model. METHODS: The SCID and
      NOD/SCID mice were injected with HL-60 cells in to the abdominal cavity in order
      to contruct the AML mouse model. The gereral status of mice was observed, the
      positive rate of CD33 in bone marrow cells was detected by flow cytometry, the
      mouse model was identified by pathologic examination. RESULTS: The tumor-forming
      rate in constructed model using SCID mouse was 30%, while the tumor-forming rate
      in constructed model using NOD/SCID mouse was 100%. CONCLUSION: Compared with
      SCID mice, the tumor-forming rate in NOD/SCID mice injected with HL-60 cells is
      high, the incidence of AML is stable, suggesting that the NOD/SCID mouse model is
      more suitable to explore the pathogenesis of leukemia.

PMID- 25948181
TI  - [Clinical and Laboratorial Characteristics of Primary Acute Myeloid leukemia with
      Philadelphia Chromosome and Inversion 16].
AB  - OBJECTIVE: To summarize the clinical characteristics as well as diagnosis and
      treatment in 1 case of acute myeloid leukemia(AML) with coexpression of Ph and
      inv(16). METHODS: A series of clinical tests, the cellular morphological,
      immunological, cytogenetic and molecular biological examinations of leukemia
      cells were performed. RESULTS: The clinical characteristics of this patient were
      very common. The cellular morphology is similar to the AML with inv(16). The
      leukemia cells were stained positively for CD13, CD33, CD34, CD117 and HLA-DR.
      Karyotypic analysis showed a complex chromosome abnormality including inv(16) and
      Ph, and the FISH analysis showed that the percentage of rearrangement of CBFbeta
      allele was over that of the BCR-ABL fusion signals. The obvious adverse events
      did not occur in this patient within 3 years. CONCLUSION: Ph as secondary
      aberration of inv(16) rarely occures in primary AML cases, and so far there have
      not been the clear criteria of diagnosis and treatment. The cytogenetic and
      molecular biology could provide the basis for diagnosis. Moreover, autologous
      hematopoietic stem cell transplantation combined with imatinib probably is one of
      the effective treatment methods.

PMID- 25948182
TI  - [Metformin Influences the Effect of Adipocytes on Leukemia Cell Chemoresistance
      through Regulation of Adipogenesis].
AB  - OBJECTIVE: To investigate the effect of metformin on 3T3-L1 preadipocyte's
      differentiation and consequently observe the anti-proliferative effects of
      metformin-treated adipocytes on leukemia cells. METHODS: Different concentrations
      of metformin were added in 3T3-L1 preadipocytes to induce maturation, the matured
      adipocytes were detected by oil red O staining and quantified by absorbance value
      (OD). Real-time PCR was used to detect the mRNA expression level of the key
      adipogenic genes PPARgamma, C/EBPalpha and FABP4(ap2). The adipocytes were co
      cultured with GFP+-THP-1 cells, 1 ug/ml of cytarabine(Ara-C) was added and
      incubated for 48 hours, the flow cytometry was used to detect the apoptosis rate
      of GFP+-THP-1 cells. Adipocyte supernatant was collected and mixed with equal
      volume of tumor lysat medium (RPMI 1640) at 1:1 to culture tumor cells. The
      leukemia cell proliferation activity was detected by CCK-8; after 48 hours of
      adding 1 ug/ml Ara-C, the protective effect on chemotherapy was assayed by using
      cytometer. RESULTS: The metformin lowered the OD value, and the expression levels
      of both adipogenic genes C/EBPalpha and FABP4 were lower than those of controls,
      while the expression level of PPARgamma mRNA was not significantly changed, the
      apoptosis rate of leukemia cells co-caltured with metformin-treated adipocytes
      was higher than that of co-cultured cells without metformin treatment. The
      adipocytes promoted the leukimia cell proliferation and protected leukemia cells
      from chemotherapy, which could be abrogated by metformin. CONCLUSION: The
      metformin can inhibit the differentiation of 3T3-L1 preadipocytes into
      adipocytes, and can regulate the protective effect of adipocytes on the
      apoptosis, proliferation and chemotherapy of leukemia cells.

PMID- 25948184
TI  - [miR-328 Inhibits K562 Cell Proliferation by Up-regulation of C/EBPalpha
      Expression].
AB  - OBJECTIVE: Our research was aim to investigate the effect of microRNA-328 (miR
      328) on proliferation of chronic myeloid leukemia(CML) cell K562 and the mediated
      effect of C/EBPalpha. METHODS: The eukaryotic expression vectors of miR-328
      targeting gene and suppressor gene (hsa-miR-328 and hsa-miR-328-inhibitor) were
      constructed, and transfected into K562 cells respectively. The mRNA expression
      levels of miR-328 and C/EBP alpha were detected by real-time fluorescence
      quantitative RT-PCR; C/EBP alpha protein expression was detected by Western blot;
      CCK-8 was used to estimate the cell viability. RESULTS: The recombinant genes of
      hsa-miR-328 and hsa-miR-328-inhibitor were successfully constructed and
      transfected into K562 cells. Fluorescent cells were observed after 24 h, and the
      visible fluorescence cells were gradually increased after 48 h or 72 h, the miR
      328 showed no effect on the mRNA expression of C/EBPalpha detected by RT-PCR.
      Meanwhile, miR-328 showed recovering effect on C/EBPalpha translation and
      inhibition of K562 cells proliferation. CONCLUSION: miR-328 has been successfully
      constructed and transfected into K562 cells, miR-328 inhibits the proliferation
      of K562 cells by up-regulation of C/EBPalpha.

PMID- 25948183
TI  - [Effects of Down-regulating PPP2R5C Expression on Expression Profile of TAL1
      related Regulating Genes in Jurkat Cells].
AB  - OBJECTIVE: Based on our previous study showing the inhibition of lenkemia T cell
      proliferation by down-regulating PPP2R5C expression, this study was aimed to
      analyze the influence of down-regulating PPP2R5 expression via RNA interference
      on genes relatied with TAL1 signaling pathway by using gene chip technique.
      METHODS: The PPP2R5C-siRNA799 was transduced into Jurkat cells by nucleofection,
      the total RNA was isolated from treated Jurkat cells after culture for 48 hours;
      the target sequences were prepared by revevse transcription after mRNA
      purification, and were hybridized with affymetrix gene expression profile chip 3'
      IVT. The original image data were collected using affymetrix gene chip scanner 3
      000, and the gene expression profile was analyzed using gene spring GX 11.0
      soflware. RESULTS: The expression of all 26 genes related with TAL1 signaling
      pathway was changed, out of which the expression of 15 genes were up-regulated
      and the expression of 11 genes was down-regulated in PPP2R5C-siRNA 799
      transfected Jurkat cells. The genes with significantly up-regulated expression
      were GATA1, TCF4, XRCC6 and TCF3, while the genes with significantly down
      regulated expression were SIN3A and RUNX1. CONCLUSION: The down-regulation of
      PPP2R5C gene expression in Jurkat cells via RNA interference to a certain degree
      can inhibit TAL1 signaling pathway genes, thereby suppresses the proliferation of
      Jurkat cells.

PMID- 25948185
TI  - [Clinical Efficacy of Dasatinib, Nilotinib and Imatinib in Newly Diagnosed
      Patients with Chronic-Phase Chronic Myeloid Leukemia: A Three-year Retrospective
      Analysis].
AB  - OBJECTIVE: To evaluate efficacy and safety of second-generation tyrosine kinase
      inhibitors (TKI) dasatinib, nilotinib and imatinib in treatment of newly
      diagnosed patients with chronic-phase chronic myeloid leukemia (CML). METHODS:
      The clinical data and follow-up results of 163 patients with chronic-phase
      chronic myeloid lenkemia(CP-CML) who were treated in our hospital during the
      nearly 3 years were analysed retrospectively, among 163 patients 47 received
      dasatinib, 43 received nilotinib and 73 received imatinib. The efficacy, disease
      progression and safety were evaluated. RESULTS: After treatment for 3 months, the
      rate of complete hematologic response(CHR) in three treatment groups were 77%,
      79% and 67%, respectivily, CHR at 12 months in three treatment groups were 92%,
      91% and 90%, respectively. By 3 months, the rates of complete cytogenetic
      response(CCyR) with dasatinib and nilotinib were higher than that with imatinib
      (55%, 53% vs 33%)(P<0.05 for both comparisons), CCyR at 12 months in three
      treatment groups were 86%, 88% vs 69% (P<0.05 for both comparisons). The rates of
      major molecular response(MMR) for dasatinib (11%) and nilotinib (9%) by 3 months
      were significantly higher than that for imatinib (1%) (P<0.05 for both
      comparisons), MMR at 12 months in three treatment groups were 49%, 50% and 28%,
      respectively (P<0.05 for both comparison). Progression to the accelerated or
      blast phase of CML occurred in 2 (4%) patients received dasatinib, 2 (5%)
      received nilotinib and 6 (8%) received imatinib. The safety profiles of these 3
      second-generation TKI treatments were similar. CONCLUSION: Both dasatinib and
      nilotinib induced strikingly higher and faster rates of complete cytogenetic
      response and major molecular response, with a statistically significant
      difference from imatinib.

PMID- 25948186
TI  - [Mechanism of Notch1 Pathway in SUP-B15 Cell Apoptosis Induced by JQ1].
AB  - OBJECTIVE: The study was aimed to investigate the possible mechanism of Notch1
      pathway in apoptosis of Ph(+) human ALL Cells(SUP-B15 cells) induced by
      bromodomain inhibitors JQ1. METHODS: The SUP-B15 cells were treated with
      different concentrations of JQ1 for different times. The cell proliferation was
      analyzed with cytotoxicity test(MTT method). Cell cycle was detected by
      fluorescence microscopy and flow cytometry. The mRNA expression of MIS2, Notch1,
      Hes1, BCR-ABL in Notch1 pathway was detected by real-time quantitative PCR.
      RESULTS: JQ1 0-4 umol/L could significantly inhibit the viability of SUP-B15
      cells treated in does-and time-dependent manner. After SUP-B15 cells were treated
      with 1,2,4 umol/L JQ1 for 48 h, the JQ1 could induce S cycle arrest in does
      dependent manner which was statistical different from the control at the same
      time (P<0.05). MIS2, Notch1, Hes1, BCR-ABL mRNA expression was down-regulated by
      JQ1 which was statistical different from the control (P<0.05). CONCLUSION: The
      JQ1 can effectively inhibit the growth and proliferation of SUP-B15 cells and the
      Notch1 pathway may be one of the important apoptosis mechanisms in Ph(+) ALL
      cells induced by JQ1.

PMID- 25948188
TI  - [Effect of YM155 on Apoptosis and Autophagy of K562 Cells].
AB  - OBJECTIVE: This study was purposed to investigate the effect of YM155, a survivin
      inhibitor, on the apoptosis and autophagy of K562 cells. METHODS: K562 cells were
      treated with YM155 at different concentration. Cell survival was analyzed by CCK
      8 assay, the cell apoptosis was detected by flow cytometry. Survivin, BCL-2 and
      beclin1 mRNA expressions were determined by RT-PCR. Survivin, BCL-2, caspase-3,
      PARP and LC-3 protein expressions were assayed by Western blot. RESULTS: YM155
      inhibited the proliferation of K562 cells in a time- and dose-dependent manners.
      With the increasing of YM155 concentration and prolonging of action time, the
      expression levels of mRNA and protein of survivin and BCL-2 decreased, while the
      expression levels of caspase-3, PARP, beclin1 and LC-3 increased. Compared with
      the YM155 group, the protein levels of LC-3 and caspase-3 were lower in YM155
      combined with 3-MA group. CONCLUSION: YM155 can inhibit K562 cell proliferation
      by inducing apoptosis and autophagy, while autophagy induction effect can enhance
      its cytotoxic effect.

PMID- 25948187
TI  - [Cohort Study on GHA and New Combined Priming Chemotherapeutic Regimens in
      Treatment of Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome].
AB  - OBJECTIVE: To explore the clinical efficacy and adverse effects of GHA(G
      CSF+homoharringtonin+cytarabine C) and new combined priming chemotherapeutic
      regimens(GHAA/GHTA) with high efficacy and low toxicity for treatment of relapsed
      and refractory acute myeloid leukemia(AML) and myelodysplastic syndrome(MDS), and
      to analyze the relation of above-mentioned regimens with the expression of co
      stimuolating molecule B7.1. METHODS: Standard GHA regimen consisting of G-CSF:
      100 ug/(m2.d) subcutaneous injection, d 0-14; homoharringtonine: 1.0 mg/(m2.d)
      intravenous drip, d 1-14; Ara-C: 7.5-10 mg/(m2.d) subcutaneous injection, q12h, d
      1-14. Other regimens as GHAA/GHTA were combined respectively with aclarubicin 20
      mg d 1-7, or pirarubicin 20 mg d 1-7. 74 patients with refractory AML and 46
      patients with MDS received these priming chemotherapy. The clinical efficacy and
      toxicity of above-mentioned priming chemotherapy were compared with 56 patients
      received routine chemotherapy (MA/TAE) respectively. And the expression of
      costimulatory molecule B7.1 on leukemia cells in patients of different subtypes
      was also detected by immunofluoressence and its relationship with clinical
      efficiency was explored. RESULTS: (1) for AML patients treated with priming
      chemotherapy, the total remission was 67.56% (CR 54.05%, PR 13.51%), which was
      much higher than that of patients received routine chemotherapy (P<0.05). The CR
      rate of AML-M2 and AML-M5 group (65.51%, 61.90% respectively) was much higher
      than that of AML other subtypes (P<0.05), and the longest remission period lasted
      for 4 years; (2) for MDS patients treated with priming chemotherapy, the total
      remission was 60.87% (CR 45.65%, PR 15.22%), which was also significantly higher
      than that of patients received routine chemotherapy (P<0.05); (3) in comparison
      with patients received standard GHA priming regimen, the remission rate of
      combined priming chemotherapy GHAA/GHTA was significantly higher both in patients
      with AML (85.18%) and MDS (81.25%); (4) side effects after chemotheropy,
      including granulocyte deficiency, thrombocytopenia and anemia etc, lasted for 7
      14 days; the severe infection rate was 1%, there were no severe bleeding, digest
      effect and damage of function in heart, liver and kidney. The therapy-related
      mortality was zero. Compared with routine chemotherapy, priming chemotherapy
      proved significantly safe and effective (P<0.05); (5) the expression rate of
      costimulatory molecule B7.1 showed large variance between AML and MDS, it was
      higher in AML-M2/AML-M5 and lower in AML of other subtypes (P<0.05). In the same
      case, B7.1 expression was positive correlated with efficiency of priming
      chemotherapy. CONCLUSION: GHA priming chemotherapy, as well as other combination
      regimens GHAA/GHTA, are well-tolerated, effective regimens for refractory AML and
      advanced MDS, without severe side effects and therapy-related mortality.
      Especially the new regimens GHAA/GHTA has better efficacy, which are proved more
      efficient than conventional GHA. Efficiency of priming chemotherapy is positive
      correlated with B7.1 expression, its mechanism will be further explored.

PMID- 25948189
TI  - [Effects of Aptamer-siRNA Nucleic Acid Compound on Growth and Apoptosis in
      Myeloid Leukemia Cell Line K562].
AB  - OBJECTIVE: To explore the effects of aptamer-siRNA nucleic acid compound on
      growth and apoptosis in myeloid leukemia cell line K562. METHODS: the changes of
      cellular morphology and structure were observed by using fluorescence microscope,
      laser confocal microscope, JEM-4000EX transmission electron microscopy; MTT assay
      were performed to evaluate the sensibility of K562 cells to aptamer-siRNA
      compound, the apoptosis was detected by DNA gel electro-phoresis. RESULTS: The
      remarkably changes of morphology and structure of K562 cells treated with 200
      umol/L aptamer-siRNA were observed under fluorescence microscopy and
      electromicroscopy. As compared with control, the aptamer-siRNA compound showed
      more inhibitory effect on K562 cells and there was significant difference
      (P<0.05). The MTT assay showed that the IC50 value of aptamer-siRNA compound for
      K562 cells was 150 umol/L. According to agarose gel electrophoresis observation,
      when the aptamer-siRNA compound showed effect on K562 cells, the typical DNA
      lader could be observed. CONCLUSION: The aptamer-siRNA compound can significantly
      induce K562 cell apoptosis, and provide reference for gene therapy of patients
      with chronic myelocytic lenkemia.

PMID- 25948190
TI  - [Effects of the Combination of Emodin and 3'-Azido-3'-Deoxythymidine on
      Proliferation and Apoptosis in leukemia KG-1a cells Transfected with Egr-1
      siRNA].
AB  - OBJECTIVE: This study was aimed to investigate the effects of emodin combined
      with 3'-azido-3'-deoxythymidine (AZT) on proliferation and apoptosis of leukemia
      cell line KG-1a cells and its mechanism. METHODS: KG-1a cells were transfected
      with Egr-1 siRNA by electroporation and divided into blank control (KG-1a),
      nonspecific control (KG-1a/NC) and Egr-1 siRNA (KG-1a/siRNA) groups. Transfection
      efficiency was tested through fluorescence microscopy and flow cytometry and the
      transfection effect was detected by using qPCR. The cell proliferation rate was
      detected with MTT method. After the cells were treated with 10 umol/L of emodin,
      3200 or 1600 umol/L of AZT and their combinations, the proliferation inhibition
      rates and the apoptosis rates of cells in 3 groups were detected with MTT method
      and FCM, respectively. RESULTS: The transfection efficiency of Egr-1 siRNA was
      found to reach more than 59.21%; as compared with blank control(KG-1a) and
      nonspectic control(KG-1a/NC), the cell proliferation in Egr-1 siRNA group
      significantly reduced (P<0.01). The combination of emodin and AZT had
      considerable synergistic inhibitory effects on proliferation of normal KG-1a
      cells and nonspecific control(KG-1a NC) cells, but the synergistic effects
      disappeared after Egr-1 gene silencing. CONCLUSION: The effects of the
      combination of emodin and AZT on proliferation and apoptosis may be related with
      Egr-1.

PMID- 25948191
TI  - [2-methoxyestradiol induced apoptosis and expression of p53 gene in human acute T
      lymphoblastic leukemia cells].
AB  - OBJECTIVE: To explore the effect of 2-methoxyestradiol (2-ME2) on apoptosis of
      human acute T lymphoblastic leukemia cells, and its underlying mechanism.
      METHODS: The growth inhibition of CEM cells was detected by MTT assay; apoptotic
      cells were detected by DNA laddering analysis; the expressions of P53 mRNA and
      protein were detected by RT-PCR and Western blot respectively. RESULTS: 2-ME2
      remarkably inhibited the CEM cell growth and the 50% growth inhibitory
      concentration (IC50) at 48 h was 2 umol/L. The DNA ladder could be detected in
      CEM cells after treating with 2 umol/L 2-ME2 for 24, 48 and 72 hours; after
      treating with 2 umol/L 2-ME2 for 24, 48 and 72 hours, a time-dependent reduction
      of P53 mRNA and protein expressions was found in CEM cells. CONCLUSION: The anti
      leukemia effect of 2-ME2 is completed through the induction of cell apoptosis.
      Down-regulation of P53 gene expression may be an underlying mechanism.

PMID- 25948192
TI  - [Efficacy Analysis of MAC Regimen as Salvage Treatment Protocol for Acute Myeloid
      Leukemia Patients Older Than 55 Years].
AB  - OBJECTIVE: To evaluate the efficacy and safety of MAC regimen in the treatment of
      acute myeloid leukemia(AML) patients older than 55 years. METHODS: A total of 33
      relapsed or non-remission AML patients older than 55 years were enrolled in this
      research. MAC regimen was given as the salvage treatment. Complete remission
      rate(CR), partial remission rate(PR), overall survival(OS), relapse-free
      survival(RFS) and adverse effect were analysed. RESULTS: CR rate after the
      salvage therapy with MAC was 51.1%, partial remission (PR) rate was 6.1%, the
      overall response rate (ORR) was 57.6%, the median OS was 8 months (1.0-66.0
      months), the median relapse-free survival (RFS) was 10.1 months (2.3-40.4
      months). Mortality related with salvage treatment in 30 days was 9.1%. Low
      incidence of severe organ damage were found. CONCLUSION: MAC can be used as a
      relative effective and safe regimen for the salvage treatment of the older AML
      patients.

PMID- 25948193
TI  - [A case report of refractory pleural effusion associated with dasatinib in the
      treatment of chronic myeloied leukemia].
AB  - OBJECTIVE: To study the clinical features and prognosis of pleural effusion
      associated with dasatinib in treatment of chronic myeloid leukemia(CML). METHODS:
      A 49 year old mal patient with CML who suffered pleural effusion(grade 3)
      associated with dasatinib was analyzed and summarized. RESULTS: the patient
      achieved complete molecular response(CMR) after treating with dasatinib 100 mg
      once daily for 3 months. However, the symptom of chest distress occured in the
      patient after dasatinib treatment for 6 months, the chest CT scan showed
      bilateral pleural effusion(grade 3), the pleural effusion related with dasatinib
      was diagnosed, therefore the diuretic and steriod drugs were given,
      thoracocentesis was also used to relieve the symptom, after treatment for 5 weeks
      the pleural effusion disappeared, but the pleural effusion recurred when the
      patient taken dasatinib again, thus the dasatimib was permanently discontinued,
      but the patient was in CMR. Six months later, the patient began to take Imatinib
      (first TKI) 300 mg/d, good effects were achieved and no serious adverse effects
      were observed. Up to now, the patient still is in CMR for 20 months. CONCLUSION:
      In the treatment of CML, appropriate TKI should be chose according to basic
      disease, and pleural effusion is one of the most common adverse effects during
      the therapy with dasatinib, close monitoring and timely intervention are
      necessary. For these patients who were intolerable to recieve the dasatinib, the
      conversion to another TKI may acquire satisfactory curative effect with tolerance
      of patients.

PMID- 25948194
TI  - [Expression Changes of beta-catenin and P-GSK-3beta in Patients with Mantle Cell
      Lymphoma].
AB  - OBJECTIVE: This study was purposed to detect the expressions of beta-catenin and
      P-GSK-3 beta in Wnt signaling pathway of patients with mantle cell lymphoma(MCL),
      and investigate its relationship with the pathogenesis of MCL. METHODS: The
      expression levels of beta -catenin protein and P-GSK-3 protein in mantle cell
      lymphoma and hyperplastic lymphadenitis were detected by using anti-beta-catenin,
      P-GSK-3beta polyclonal antibody and S-P staining technique. RESULTS: The abnormal
      expression of beta-catenin protein(73.33%) in mantle cell lymphoma group was
      significantly higher than that (6.7%) in reactive lymph node hyperplasia group
      (P<0.05); and the positive rate of P-GSK-3 beta(66.67%) in mantle cell lymphoma
      group was significantly higher than that (16.67%) in reactive hyperplasia of
      lymph node group (P<0.05). Spearman correlation analysis showed that there was
      obvious positive correlation (R=0.852, P<0.01). CONCLUSION: The abnormal high
      expressions of beta-catenin and P-GSK-3 beta protein have been confirmed to
      appeare in mantle cell lymphoma.

PMID- 25948195
TI  - [Antiproliferative Effect of Specific Inhibitor XAV939 for beta-catenin on MCL
      Jeko-1 Cells].
AB  - OBJECTIVE: To investigate the effect of short hairpin RNA (shRNA) and XAV939, a
      specific inhibitor for beta-catenin, on growth and apoptosis of mantle cell
      lymphoma(MCL) Jeko-1 cell line. METHODS: beta-catenin shRNA eukaryotic expression
      vector was transfected into Jeko-1 cells, the antiproliferative effect of shRNA
      on Jeko-1 cells was detected by RT-PCR and Western blot. The proliferation
      inhibitory rate of Jeko-1 cells treated by different doses of XAV939 was assayed
      by MTT method; the level of apoptosis of Jeko-1 cells was detected by flow
      cytometry; the expression levels of apoptosis-related protein BCL-2, BAX,
      CyclinD1, C-MYC and Caspase-3 in Jeko-1 cells were determined by Western blot.
      RESULTS: The expression of beta-catenin mRNA and growth of Jeko-1 cell line were
      inhibited by shRNA; after Jeko-1 cells treated with 0,2 and 8 umol/L XAV939 for
      48 hours, the cell proliferation rate decreased, while the cell apoptosis rate
      increased, the expressions of apoptosis-related protein BCL-2, CyclinD1 and C-MYC
      were down-regulated, on the contrary, the expression of BAX and caspase-3 were up
      regulated. CONCLUSION: The specific inhibition of beta-catenin can inhibit Jeko-1
      cell proliferation and promote the cell apoptosis.

PMID- 25948196
TI  - [Clinical significance of bone marrow morphological examination and tumor marker
      detection for lymphoma diagnosis and prognosis].
AB  - OBJECTIVE: This study was aimed to evaluate the significance of bone marrow(BM)
      morphological examination and many tumor marker(TM) detection, especially
      carcinoembryonic antigen (CEA), cancer antigen 125(CA125), cancer antigen 15-3
      (CA15-3) and serum ferritin (SF) for lymphoma diagnosis and prognosis. METHODS: A
      total of 47 confirmed patients with lymphoma in our hospital from January 2012 to
      October 2013 and 20 health peoplels as normal controls were performed with bone
      marrow morphological examination, at the same time, the electrochemistry
      luminescent technique was applied for detecting levels of TM (especially CEA,
      CA125, CA15-3 and SF) in serum samples of lymphoma patient and normal controls,
      then the BM immature lymphocyte counts of these people and clinical parameters
      were analyzed for diagnosis and prognosis. RESULTS: There was significant
      differences in all the four TM levels between serum samples of lymphoma patients
      and normal control (P=0.029, P=0.000, P=0.005, P=0.000). These TM levels had no
      correlation with age, sex white blood cell, lymphocyte, platelet counts and
      anemia of lymphoma patients (P>0.05). It was also found that the patients with
      elevated TM levels had high BM immature lymphocytes (lymphoma cells) counts, B
      symptoms, advanced clinical stage and high IPI index (P<0.05). The CA15-3 and SF
      levels in serum samples of lymphoma patients with BM infiltration were higher
      than that in lymphoma patients without BM infiltration (P=0.002, P=0.000).
      CONCLUSION: Combination of BM morphological examination with serum TM level
      detection plays an important role in diagnosis, clinical stage and prognosis
      evaluation of lymphoma patients. It is also very important for assessing BM
      infiltration status of lymphoma patients.

PMID- 25948197
TI  - [Clinical analysis of 13 patients with primary bone lymphoma].
AB  - OBJECTIVE: To analyse the clinical featuers, prognositic factors and treatment
      outcomes of primary bone lymphoma(PBL). METHODS: The clinical data of 13 patients
      with PBL in our hospital from 2005 to 2014 were analysed retrospectively.
      RESULTS: The median age of these patients was 40 (25-71) years old, ostealgia was
      the initial symptom(100%). The main histologic type was diffuse large B cell
      lymphoma (DLBCL) (11/13, 84.6%), and among other 2 cases 1 case was anaplastic
      large cell lymphoma(ALCL) and other 1 case was B lymphoblastic lymphoma. All 13
      cases were treated with chemotherapy, 6 cases got complete remission(46.2%) and 7
      cases got partial remission(53.8%). There was no statistical relation of age,
      sex, stage, beta2-MG level, LDH level, pathological type and the application of
      rituximab with the complete remission rate (P>0.05). After the median follow up
      of 12 (3-72) months, 3 cases died of diease progression and 6 cases maintained in
      complete remission, the median progression-free survival was 13 (2-72) months.
      CONCLUSION: The most common histologic type is DLBCL, its main treatment method
      is the combined chemical therapy, but the role of rituximab in treatment is not
      clear, thus larger clinical trial is necessary.

PMID- 25948198
TI  - [Clinical Analysis of 41 Patients with Burkitt's lymphoma].
AB  - OBJECTIVE: To summarize the clinical characteristics of Burkitt's lymphoma.
      METHODS: Clinical data of 41 Burkitt's lymphoma patients, treated from Jannuary
      2009 to June 2014 in Chinese PLA General Hospital, were analyzed retrospectively.
      RESULTS: Out of the 41 patients, 33 were males and 8 were females, with a median
      age of 13 (range, 1-67), 18 cases (43.9%) were in Ann Arbor stage I/II, and 23
      cases (56.1%) were in stage III/IV. The commonest pathologicalal sites were head
      and neck (23 cases, 56.1%), and then the abdominal (41.5%), bone marrow (22.0%)
      and central nervous system (22.0%) could also be involved, while 7 cases (17.1%)
      were patients transformed into acute lymphocytic leukemia-type L3, 18% cases
      (3/16) were infected by EBV and 29.9% cases (6/38) were infected by HBV, 29 cases
      were treated with chemotherapy, their overal remission rate was 93.1(27/29
      cases), 2-year overall survival rate(OS) was 83.3%(10/12 cases); 13 cases were
      treated with rituximab, their remission rate was 92.3%(12/13 cases), and 2-year
      OS was 66.7%(4/6 cases). CONCLUSION: The 41 cases are more similar to the
      sporadic Burkitt's lymphoma, but the median age of its occurence is more younger,
      while the most common pathological sites are head and neck, and the short-term
      and high intensive chemotherapy with rituximab can obviously elevate remission
      rate for adult patients and prolong their survival time.

PMID- 25948199
TI  - [Serum 25-Hydroxyvitamin D3 Level in Peripheral Blood of Patients with Non
      Hodgkin's Lymphoma and Its Clinical Significance].
AB  - OBJECTIVE: To explore the correlation between the level of serum 25-hydroxyvi
      tamin D3 and the development and prognosis of NHL in order to provide the
      theoretical basic for the diagnosis, treatment and prognosis of NHL. METHODS: The
      serum 25-hydroxyvitamin D's level of 84 NHL patients and 60 healthy persons was
      detected by using enzyme-linked immunsorbent assay. RESULTS: The level of serum
      25-hydroxyvitamin D3 in NHL group was significantly lower than that in normal
      control group and the difference between NHL patients and normal controls was
      statistically significant. The stage and cell source of NHL patients showed
      little effect on the level of 25-hydroxyvitamin D3. There were significant
      differences of the level of 25-hydroxyvitamin D3 in different group and sites of
      origin as well as in presence or absence of bone marrow infiltration.
      CONCLUSIONS: The level of 25-hydroxyvitamin D3 can be considered as tumor burden
      index of NHL and can be used to evaluate the prognosis of NHL.

PMID- 25948200
TI  - [Clinical and Pathological Analysis of 9 Patients with Primary Breast Diffuse
      Large B-cell Lymphoma].
AB  - OBJECTIVE: To explore the clinical features, diagnosis and treatment of primary
      breast diffuse large B- cell lymphoma (PBDLBCL). METHODS: Clinical records of 9
      PBDLBCL patients treated in Department of Hematology of Yijishan Hospital
      Affiliated to Wannan Medical College from August 2001 to January 2014 were
      analyzed retrospectively. RESULTS: All of the 9 patients were female, with an
      average age of 48 years (range 28 to 75), 8 cases had unilateral breast tumors
      and 1 case had bilateral. According to the Ann Arbor stage standard, 2 cases were
      of stage IE and 7 were IIE. None of them was concurrent with B symptoms; 6 cases
      had IPI (International prognostic Index) score 0 and 3 had score 1. 2 cases
      belonged to germinal center B cells type (GCB) and 7 belonged to non-GCB. Double
      Hit lymphomas were presented in 3 cases. Out of 9 cases, 3 cases were diagnosed
      by using tubular needle biopsy, 5 cases were diagnosed by using resection of
      breast mass, and 1 case was diagnosed by using modified radical mastectomy. 1
      case received radical mastectomy, 1 case received unilateral breast removal, 1
      case gave up, 1 case received mass excision with chemotherapy and radiotherapy, 5
      cases received mass excision with chemotherapy and 1 case received central
      prophylaxis. A complete response (CR) was observed in 6 cases after first-line
      chemotherapy. The median follow-up time was 18 months (range 0.1 to 150), 3 cases
      relapsed and 5 cases died. CONCLUSION: PBDLBCL mostly occurs in female. The main
      pathological type is non-GCB coupled with Double-Hit lymphoma. Tubular needle
      biopsy offers benifit in the diagnosis of PBL, R-CHOP or R-CHOP combined with
      chemotherapy/radiotherapy produce best outcome among all the treatments.
      Intrathecal injection of chemotherapy drugs may help to prevent recurrence of PBL
      central.

PMID- 25948201
TI  - [Clinical efficacy of dexamethasone, methotrexate combined with cyclophosphamide
      for treatment of patients with peripheral T-cell lymphoma].
AB  - OBJECTIVE: This study was aimed to investigate the clinical efficacy of
      dexamethasone, methotrexate combined with cyclophosphamide for treatment of
      patients with peripheral T-cell lymphoma (PTCL). METHODS: Twenty-one patients
      with peripheral T-cell lymphoma were selected as control group, which were
      received CHOP; twenty-nine patients with peripheral T-cell lymphoma were selected
      as treatment group, which were received Hyper-CVAD. Clinical efficacy were
      observed after treatment. RESULTS: In control group 6 patients achieved complete
      remission(CR), 4 patients achieved partial remission(PR), the total response rate
      of control group was 47.6%; in treatment group 15 patients achieved CR, 7
      patients achieved PR, the total response rate of treatment group was 75.9%, and
      the total response rate of treatment group was significantly higher than that of
      control group. The incidence rates of cardiac dysfunction, peripheral neuropathy,
      anaemia and leucopenia between the two groups had no significant difference. The
      average progress free survival (PFS) of treatment group was 26.106 months, which
      was significantly higher than that of control group. CONCLUSION: The clinical
      efficacy of dexamethasone, methotrexate combined with cyclophosphamide for
      treatment of patients with peripheral T-cell lymphoma has been confirmed to be
      satisfactory and it may be used in clinic.

PMID- 25948202
TI  - [Safety and efficacy evaluation of gemcitabine combined with oxaliplatin for the
      treatment of patients with lymphoma].
AB  - OBJECTIVE: To investigate the short-term efficacy and safety of GEMOX regimen for
      the treatment of lymphoma, so as to provide the reference for further rational
      selection of chemotherapy. METHODS: A total of 61 patients with relapse and
      refractory non-Hodgkin's lymphoma (NHL) treated with chanotherapy of GEMOX
      regimen from 2010 Jannary -2013 year were selected, and their clinical data were
      collected, and the short-term efficacy, toxic effects and short-term survival
      were analyzed. RESULTS: The improved rate of B symptom was 86.36%; the LDH level
      in 38 cases with high LDH level after chemotherapy all obviously decreased; the
      ORR and CBR in 64 patients after treatment were 68.75% and 87.50% respectively;
      the comparison of ORR and CBR between patients with different IPI score showed
      significantly statistical difference (P<0.05). The adverse reactions mainly
      observed in blood and digestive tract, but were mild; adverse reactions were
      reduced or disappeared after stoping drugs or symptomatic treatment. The median
      progression-free survival time of patients was 10.5 months. CONCLUSION:
      Gemcitabine combined with oxaliplatin for treatment of relapse-refractory
      lymphoma shows singnificant efficacy and low toxicity, this regimen can be used
      as a second-line chemotheray in clinic.

PMID- 25948203
TI  - [Inducing effect of chidamide on apoptosis of multiple myeloma cells and its
      relerance to DNA damage response].
AB  - OBJECTIVE: This study was aimed to explore the effect of a novel histone
      deacetylase inhibitor Chidamide on apoptosis of human multiple myeloma(MM) cells
      and its relevance to DNA damage response(DDR). METHODS: The cell proliferation
      was detected by MTT method, apoptosis and cell cycle distribution were analyzed
      by flow cytometry, the expression levels of targeted proteins were detected by
      Western blot, the DNA damage response was blocked by ATM kinase inhibitor KU
      55933. RESULTS: Chidamide inhibited RPMI 8226 cell proliferation in dose- and
      time-dependent manner and its IC50 values of 24,48,72 h were 9.6, 6 and 2.8
      umol/L respectively. Chidamide induced cell cycle arrest of RPMI 8226 cells in
      G0/G1 phase by upregulating the expression of P21. Chidamide triggered caspase-3
      dependent apoptosis and upregulated expression of DDR-related proteins including
      gammaH2AX, pATM in RPMI 8226 cells. Pretreatment with ATM kinase inhibitor KU
      55933 down-regulated expression of DDR related proteins induced by chidamide,
      thereby inhibiting DNA damage response and finally resulting in suppression of
      apoptotic cell death. CONCLUSION: Proliferative inhibtion, cell cycle arrest and
      apoptosis of multiple myeloma cells induced by chidamide involve DDR.

PMID- 25948204
TI  - [Clinical Significance of ID4 Gene Mehtylation in Demethylation-Treated MDS Cell
      Line and 2 MDS Patients].
AB  - OBJECTIVE: To evaluate significance of ID4 gene mehtylation in demethylating
      myelodysplastic syndrome(MDS) cell Line MUTZ1 and 2 patients with MDS. METHODS:
      The methylation-specific PCR (MS-PCR) and reverse transcription-PCR (RT-PCR) were
      applied to identify the methylation status and gene expression of ID4 gene in MDS
      cell line MUTZ1, a patient with aplastic anemia(AA) and a donor with normal bone
      marrow (NBM). RT-PCR was applied to detect the ID4 gene expression status in
      MUTZ1 cell line treated with decitabine at 3 different concentrations. Then
      bisulfite sequencing PCR (BSP) was applied to detect ID4 gene methylation status
      in 2 MDS parients treated with decitabine. RESULTS: The MDS cell line MUTZ-1
      displayed a complete methylation of ID4 gene promoter with little mRNA
      expression. Inversely, bone marrow of an AA patient and NBM showed complete
      unmethylation of this gene with intensity mRNA expression. With the increase of
      decitabine concentration, ID4 gene mRNA expression was more and more increased.
      After decitabine treatment, ID4 gene methylation-positive frequencies of both the
      2 MDS patients were much more decreased than that of the first treatment. So, ID4
      gene mRNA expression inhibited by promoter hypemethylation could be recovered by
      using demethylation medicine. CONCLUSION: ID4 as a new potential anti-oncogene
      suggests that its methylation may become a marker for selection and assessment of
      therapeutic schedules in patients with MDS.

PMID- 25948205
TI  - [Correlation of the Desialylation of Platelets with Efficacy of the First-line
      Therapy for ITP].
AB  - OBJECTIVE: To detect desialylation of platelets in primary immune
      thrombocytopenia(ITP) patients with FITC-labelled ECL and RCA-1, and compare the
      correlation of the desialylation level and the efficacy of first-line therapy for
      ITP. METHODS: Before treatment, 48 ITP patients were selected and their levels of
      ECL and RCA-1 were detected with flow cytometry. RESULTS: The desialylation level
      in the different efficacy groups by using the first-line therapy of
      corticosteroids and (or) intravenous immunoglobulin G (IVIG) had a statistically
      significant difference (P<0.05). The correlation analysis showed negative
      relation of the therapeutic efficacy with desialylation level, that is to say,
      the more high of desialylation level, the more poor therapeutic efficacy of the
      first-line therapy. CONCLUSION: The desialylation level of platelets in ITP
      patients is related with the first-line therapeutic efficacy, the efficacy for
      patients with high desialylation level is poor, suggesting that the FcR
      independent pathway exists in clearance of platelets in ITP patients. Therefore,
      the desialylation level of platelets may suggest the first-line therapeutic
      efficacy for ITP patients to a certain degree, and may be used as a potential
      target for the treatment of refractory ITP.

PMID- 25948206
TI  - [Effects of the interleukin-21 expression in patients with immune
      thrombocytopenia and its regulation by high-dose dexamethasone].
AB  - OBJECTIVE: To investigate the correlation of immunologic thrombocytopenia(ITP)
      pathogenesis with the abnormal expression of IL-21, and to explore the
      association of high-dose dexamethasone (HD-DEX) treatment with the IL-21
      expression. METHODS: 26 newly diagnosed ITP patients and 24 healthy controls were
      enrolled in this study. The mononuclear cells and serum were obtain from density
      gradient centrifugation in the newly diagnosed ITP patients before HD-DXM
      treatment, and the samples of healthy controls were also used for assays. The
      protein and mRNA expression of IL-21 on peripheral blood mononuclear cells(MNC)
      were determined by flow cytometry and real-time reverse-transcription polymerase
      chain reaction. Plasma levels of IL-21, IFN-gamma and IL-4 were determined by
      enzyme-linked immunoabsorbent assay (ELISA). RESULTS: IL-21 expression on
      mononuclear cells was significantly higher in ITP patients (13.07%) than that in
      normal controls (8.2%), the ratio of IL-21/GAPDH mRNA expression on MNC was
      significantly higher in ITP patients (9.524+/-0.97) than that in normal controls
      (3.701+/-0.60, P<0.01). After HD-DXM therapy, the ratio of IL-21/GAPDH mRNA
      decreased significantly (5.87+/-1.21) as compared with the level before
      treatment. Significantly high levels of serum IL-21, IFN-gamma and lower IL-4
      were found in ITP patients, as compared with healthy controls. Serum IL-21 and
      IFN-gamma levels in ITP patients decreased significantly after HD-DXM
      administration (P<0.01), while post-treatment levels of IL-4 were increased
      significantly, compared with the levels before treatment (P<0.01). CONCLUSION:
      Therapeutic effect of DXM on ITP associates with down-regalation of IL-21
      expression. The increased expression of IL-21 involves in the pathogenesis of
      ITP.

PMID- 25948207
TI  - [Short and long term efficacy of immunosuppressive therapy and survival in adult
      severe aplastic anemia].
AB  - OBJECTIVE: To evaluate the short and long term therapeutic efficacy of the
      immunosuppressive therapy(IST) for adult severe aplastic anemia(SAA), and to
      analysis the relationship between the clinical factors(age, typing, lymphocyte
      percentage, reticulocyte percentage, neutrophil count) and the response to IST.
      METHODS: The response rate of 39 patients received the IST between September 2009
      and September 2013 in our hospital was assayed, the effective time in which all
      patients had hematologic response, and the survival rate at the first year were
      analyzed. The survival rates, the average amounts of the RBC and Plt transfusion
      per month in the first year were compared by using chi2 test between the IST
      group and the non-IST group; the multinomial logistic regression was used to
      analyze the relationship between the clinical factors and the response to IST.
      RESULTS: The response rates of the 39 SAA patients at the first month, the third
      month, the sixth month and the first year were 29.73%, 70.27%, 75.68%, 86.49%,
      respectively. The median effective time of hematologic response in all patients
      had was 61.5 d(10 d-344 d). The survival rate of the IST group was 92.31%, which
      was much higher than that of the non-IST group (P<0.05). The average amounts of
      the RBC and Plt transfusion per month at the first year in the IST group were
      1.04(0.13-2.78)*400 ml and 1.38(0.17-5.10)*200 ml, respectively, which were much
      lower than those in the non-IST group (P<0.01). Among the five clinical factors,
      the age, lymphocyte percentage and neutrophil count related to the response of
      IST (P<0.05). CONCLUSION: The response rate of the 39 SAA patients received IST
      is 86.49% at the first year, and their long term survival is better than that of
      non-IST group. The age, lymphocyte percentage and neutrophil count relate to the
      response of IST.

PMID- 25948208
TI  - [Effect of Compound Zaofan Pill on Bone Marrow MVD and VEGF of Patients with
      Chronic Aplastic Anemia].
AB  - OBJECTIVE: To investigate the clinical efficacy of compound Zaofan pill combined
      with cyclosporine and androgen for treatment of patients with chronical aplastic
      anemia(CAA), and its effect on bone marrow microvessel density(MVD) and vascular
      endothelial growth factor(VEGF) of CAA patients. METHODS: A total of 76 cases of
      CAA were randomly divided into group 1 and group 2, among them the group 1 (38
      cases) was treated with cyclosporine and androgen alone, while the group 2(38
      cases) was treated with compound Zaofan pill combined with cyclosporine and
      androgen. Samples of 20 cases with normal bone marrow were used as controls. The
      clinical effects of each groups were observed, and the mean bone marrow MVD and
      VEGF levels were detected before and after half a year's treatment. RESULTS: The
      mean bone marrow MVD and VEGF levels in CAA group before treatment were
      significantly lower than that in normal control group, but bone marrow MVD and
      VEGF levels in 2 groups significantly increased after treatment. Group 1 showed
      the cure and response rate of 15.8%, while group 2 showed the cure and response
      rate of 44.7%, there was significant difference between the two groups (P<0.05)).
      There was no significant difference of bone marrow MVD and VEGF expression before
      treatment between group 1 and group 2. After treatment, bone marrow MVD and VEGF
      expression of group 2 were significantly higher than pre-treatment, moreover the
      bone marrow MVD and VEGF expression in group 2 were significantly higher than
      that in group 1. CONCLUSIONS: The compound Zaofan pill combined with cyclosporine
      and androgen can obviously increase the levels of MVD and VEGF in bone marrow,
      and improve the efficacy of treatment in CAA patients.

PMID- 25948209
TI  - [Correlation between the Expression of microRNA 451 in Red Blood Cells and
      Chronic Mountain Sickness].
AB  - OBJECTIVE: To investigate the correlation between the expression of microRNA-451
      in red blood cells and chronic mountain sickness(CMS). METHODS: Peripheral blood
      samples were collected from emigrant CMS patients (28 cases), localized CMS
      patients (12 case), emigrant healthy people (24 case) and localized healthy
      people (22 case). The microRNA-451 expression in red blood cells was measured by
      the RT-PCR. The results combined with the clinical data of patients were
      analysed. RESULTS: The expression of microRNA-451 in emigrant CMS patients was
      higher than that in emigrant healthy people (P<0.05); the expression of microRNA
      451 in localized CMS patients was higher than that in localized healthy people
      (P<0.05); the microRNA-451 expression had no statistical difference between
      emargant and localized healthy people. The level of hemoglobin in CMS patients
      was positively correlated with the expression of microRNA-451 in red cells
      (r=0.701). CONCLUSION: There is a certain level of microRNA-451 in healthy
      people, the expression of microRNA-451 in CMS patients is significantly higher
      than that in healthy people. MicroRNA-451 may play an important role in the
      process of chronic mountain sickness.

PMID- 25948210
TI  - [Risk factors and outcome of invasive fungal infection in 79 patients received
      allogeneic hematopoietic cell transplantation].
AB  - OBJECTIVE: To study the incidence, risk factors and outcome of invasive fungal
      infection(IFI) in the recipients with allogeneic hematopoietic cell
      transplantation(HSCT). METHODS: 79 cases received HSCT in our hospital from
      January 2005 to November 2014 with complete data were analyzed retrospectively
      according to the diagnostic criteria of IFI. the clinical features, risk factors
      and outcome of IFI were investigated and analysed. RESULTS: 17 cases of IFI were
      diagnosed, among them 13 cases were defined in clinic and 4 cases were possible.
      The median time of IFI occurence was 112 days(9-1931 d). The recurrence-free
      survival rate in non-infection and infection groups were 61.2% and 35.2%
      respectively. By single-factor analysis, the matching, II and IV degree of aGVHD
      were the risk factors of IFI, and the sex, protopathy, glucocorticoid used before
      infection were the risk factors of the death outcome. Multivariate analysis may
      indicated that the matching, II-IV degree of aGVHD and glucocorticoid used before
      infection were associated with IFI and outcome. CONCLUSION: The patients received
      HSCT and having many risk factors are more likely predisposed to IFI. A greater
      dose of glucocorticoid used before infection is more likely to results in death,
      morever avoiding the risk factors may reduce the incidence of IFI, and the
      retrospecion of immunosupperssor dose used within 30 days before infection may
      improve prognosis.

PMID- 25948211
TI  - [Construction of Lentivirus Vector Carrying HGF and Exploration of Transfection
      Condition of Rat Adipocyte-derived Mesenchymal Stem Cells].
AB  - OBJECTIVE: This study was to construct the lentivirus vector carrying hepatocyte
      growth factor (HGF) gene and to explore the condition for transfecting the
      adipocyte-derived mesenchymal stem cells (ADSC) by HGF lentivirus. METHODS: The
      target gene was obtained from plasmid carrying HGF gene by PCR and was cloned
      into GV287 vector. The recombinant GV287-HGF vector plasmid and lentivirus
      packing plasmid were co-transfected into 293 T cells to generate HGF lentivirus,
      and the virus titer was assayed, then the ADSC were transfected by using
      recombinant HGF lentivirus, and the optimal multplicity of infection (MOI) was
      detected. RESULTS: The PCR product of HGF gene was consistent with expectant
      sizes, suggesting that the electrophoretic result of recombinant GV287-HGF
      plasmid PCR product was correct. The sequencing analysis of cleaved product
      showed consistance of obtained results with the sequences of target gene,
      suggesting correct construction of recombinant lentivirus carrying HGF gene. The
      ELISA showed that the virus tilter was 5*10(8) TU/ml. The optimal MOI for
      transfecting ADSC with recombinant lentivirus carrying HGF gene was 50.
      CONCLUSION: The lentivirus vector expressing human HGF gene has been constructed,
      and transfected the ADSC succesfully. This study lays a foundation for further
      stadying the ADSC over-expressioning HGF, treating the radiation damage of bone
      marrow and impartant internal organs.

PMID- 25948212
TI  - [Investigation on the internalization pathway of microparticles into human
      umbilical cord endothelial cells].
AB  - OBJECTIVE: To investigate the mechanisms underlying the incorporation of
      microparticles(MP) derived from human bone marrow mesenchymal stem cells (MSCs)
      into human umbilical cord endothelial cells (HUVECs). METHODS: MPs were isolated
      from the supernatants of MSCs which had exposed to a hypoxia/serum-deprivation
      condition. Electron microscope was used to identify the MPs. The surface molecule
      profile was evaluated with the bead-based flow cytometry technique. The
      expression level of the phosphatidylserine receptor (PSR) was detected by
      immunofluorescence cytochemistry. MPs were co-cultured with HUVECs in the
      presence or absence PSR-antibody, and the internalization of MPs was observed
      with laser scanning microscopy. RESULTS: The MPs derived from MSCs expressed
      highly PS, while PSR expressed on the surface of HUVECs. The confocal result
      revealed that MPs could quickly be uptaken by the endothelial cells, and mainly
      distributed in the cytoplasm surrounding of the nuclei. The internalization of
      MPs reduced significantly after PSR specific blockage. CONCLUSION: The reaction
      between PS on the MP and the PSR of HUVECs plays an important role in the
      internalization of MSC-MPs.

PMID- 25948213
TI  - [Isolation and Biological Characteristics of Rabbit Bone Marrow Plug-derived
      Mesenchymal Stem Cells].
AB  - OBJECTIVE: Though the rabbit is one of most widely used experimental animals for
      medical regenerative research, it remains difficult to culture mesenchymal stem
      cells (MSC) on a in large scale due to the extremely lower number and
      hematopoietic cell contamination. This study was aimed to establish a novel
      protocol to generate rabbit MSC by culturing bone marrow plugs instead of bone
      marrow cells so as to obtain a large amount of MSC with higher proliferation and
      self-renewal properties. METHODS: The primary MSC were generated from collagenase
      digested bone marrow plugs and bone marrow cells, respectively. The surface
      antigen profile of MSC was analyzed with flow cytometry and the cells were
      induced to differentiate into osteoblasts and adipocytes. The proliferation
      capacity of MSC were assessed by CCK-8 method. To test their self-renewal
      property, the colony forming unit-fibroblast assay was performed. Moreover, the
      cell yields of passage 1, 2, 3 and 4 were calculated. RESULTS: The bone marrow
      plug-derived MSC shared the typical fibroblast-like morphology same as bone
      marrow cells derived MSC. Moreover, the ratio of CD45 positive hematopoietic
      cells in bone marrow plug-derived MSCs was significantly lower than that of bone
      marrow cell-derived MSC. The results of multi-differentiation experiments showed
      that bone marrow-plug-derived MSC exhibited similar multi-potent property to
      their bone marrow counterparts. In addition, the results of CCK-8 and CFU-F assay
      demonstrated that bone marrow plug-derived MSC grew more robustly and more CFU-F
      were formed in the culture plates, which indicated that the cells possessed
      higher proliferation and self-renewal capacities. Promisingly, a larger amount of
      cells were harvested via using the new protocol. CONCLUSION: The purity and
      yields of the bone marrow plug-derived MSC are satisfactory compared with
      previous rabbit MSC isolation methods. The findings may be helpful for the
      research of regenerative medicine.

PMID- 25948214
TI  - [Enrichment and Biological Characteristics of Peripheral Blood-derived
      Mesenchymal Stem Cells in Rats].
AB  - OBJECTIVE: To explore the effective method for enrichment of rat peripheral blood
      derived mesenchymal stem cells(PBMSC) and study the cell biological
      characteristics. METHODS: Peripheral mononuclear cells were isolated by density
      gradient centrifugation from blood of 4 week old rats after G-CSF mobilization.
      Thereafter, the fibroblast-like cells were acquired by plastic-adherent culture,
      and the proliferation curve was assayed. For analyzing surface markers of the
      second generation cultured isolated PBMSC, both flow cytometry(CD90, CD44, CD29,
      CD45, CD11b and CD79a) and immunocytochemical staining(CD73, CD105, CD34 and HLA
      DR) methods were used. Furthermore, the differentiation capacities of PBMSC into
      osteocytes, chondrocytes and adipocytes were identified. RESULTS: (1) The
      adherent cells displayed typical colony-forming unit fibroblast(CFU-F) growth
      pattern after 6-7 day of primary culture and reached 80% confluence after 21 days
      of culture. The passaged PBMSC possessed high proliferative capacity and spindle
      growth pattern and was able to grown into exponential phase next day with a
      doubling time of 39.2 h. (2) PBMSC expressed mesenchymal markers such as CD90,
      CD44, CD29, CD73 and CD105, but failed to expressed markers of CD45, CD11b,
      CD79a, CD34 and HLA-DR. (3) After 21 days of culture in osteogenic, chondrogenic
      and adipogenic differentiation media, calcifying nodules, intracellular
      glycosaminoglycans and lipid droplets could be found by alizarin red, alcian blue
      and oil red-O staining, respectively. CONCLUSION: PBMSC can be enriched from rat
      peripheral blood with high purity and abundance by our methods. The growth and
      phenotypic characteristics of the isolated PBMSC are consistent with that of well
      known MSC, and these cells possess the capability to multi-lineage mesoderm
      differentiation.

PMID- 25948215
TI  - [Influence of TLR2- and TLR4-activated Mesenchymal Stem Cells on Migration of
      Cord Blood CD34+ Cells].
AB  - OBJECTIVE: This study was aimed to investigate the possible effect of Toll-like
      receptors 2 (TLR2) and Toll-like receptors 4 (TLR4) on the migration function of
      umbilical cord blood (UCB) CD34+ hematopoietic stem/progenitor cells induced by
      bone marrow-derived mesenchymal stem cells (MSCs) and to explore the underlying
      mechanism. METHODS: The expression of TLR2 and TLR4 on MSC was detected with flow
      cytometry. After the MSC were pretreated with TLR2 agonist (PAM3CSK4) and/or TLR4
      agonist (LPS), the supernatants were collected. The effect of the supernatants on
      the migration of CD34+ cells was evaluated with chemotaxis assays. Alterations of
      chemokine (SDF-1) secreted by MSC in the supernatants were assayed by ELISA.
      RESULTS: The expression levels of TLR2 and TLR4 were (31.5+/-4.6)% and (85.6+/
      6.7)% respectively. Compared with the blank group, the migration ability of CD34+
      cells increased significantly in control, LPS and/or PAM3CSK4 groups (P<0.01).
      Further study found that LPS and/or PAM3CSK4 enhanced the chemotactic ability of
      CD34+ cells (P<0.05), but the concentration of SDF-1 was not changed
      significantly in all of LPS and/or PAM3CSK4 groups (P>0.05) in comparison with
      the control group. CONCLUSION: TLR2 and TLR4 signalings may indirectly increase
      the migration of CD34+ hematopoietic stem/progenitor cells by modulating BM-MSC
      functions, which may not significantly correlate with the production of chemokine
      SDF-1 by MSCs.

PMID- 25948217
TI  - [Sequence Analysis of the UGT1A1 Gene Untranslated Region in Chinese Han
      Population].
AB  - OBJECTIVE: To analyze the 5' and 3'-untranslated region sequences of the UGT1A1
      gene in Chinese Han population and to find polymorphic variants within the
      untranslated region. METHODS: Genomic DNA was extracted from peripheral
      leukocytes in 220 healthy Han individuals. The 5' and 3'-untranslated region
      sequences of the UGT1A1 gene were amplified by polymerase chain reaction, and
      followed by DNA sequencing. RESULTS: Two polymorphic loci were identified in the
      5'-untranslated region of the UGT1A1 gene with -64(G/C) and A(TA)6TAA/A(TA)7TAA
      in TATAA box region among Chinese Han population. Genotype frequencies were 98.4%
      (G) and 1.6% (C) in -64 locus of the UGT1A1 gene among the 220 individuals. The
      allele frequency of A(TA)6TAA and A(TA)7TAA within the promoter region was found
      to be 93.4% and 6.6%, respectively. Two polymorphic loci of 1813(C/T) and
      1941(C/G) were detected in the 3'-untranslated region of the UGT1A1 gene, they
      showed a homozygous state at two loci with cosegregation pattern at 1813 and 1941
      locus. The haplotype frequencies were 73.6% (CC/1813+CC/1941) and 26.4%
      (TT/1813+GG/1941) for 1813 and 1941 loci in the UGT1A1 gene. CONCLUTION:
      Cosegregation pattern, at 1813 and 1941 locus with homozygous state in the 3'
      untranslated region of the UGT1A1 gene may be selected from the human genome
      among Chinese Han population. More studies should be focused on the mechanism of
      homozygous cosegregation.

PMID- 25948216
TI  - [Mannan-Binding Lectin Inhibits Candida Albicans-Induced DC Maturation and
      Cytokine Secretion].
AB  - OBJECTIVE: To investigate the effects of mannan-binding lectin (MBL) on the
      maturation and cytokine secretion of human dendritic cells (DC) induced by
      Candida albicans (C. albicans). METHODS: The plastic-adherent mononuclear cells
      were prepared from the blood of healthy adult volunteers. The human peripheral
      blood mononuclear cells-derived dendritic cells (MNC-DC) were induced by 5-day
      culture in medium supplemented with rhGM-CSF and rhIL-4, and then cultured for 2
      days in presence or absence of C. albicans at varying concentration of human MBL
      ranging from 1 to 20 mg/L. DC's shape and characters were observed under inverted
      microscopy, the expression of CD83 and CD86 on DC was analyzed by FACS. The
      levels of TNF-alpha and IL-6 were detected by ELISA. FACS also was used to
      investigate the interaction of MBL with immature DC(imDC) and C. albicans.
      Western blot was used to detect C. albicans-induced IkappaBalpha phosphorylation
      and p65/NF-kappaB translocation in DC. RESULTS: MBL at higher concentrations (10
      20 mg/L) down-regulated the expression of CD83 and CD86 on the monocyte-derived
      dentritic cells(MoDC) induced by C. albicans, and inhibited the production of TNF
      alpha and IL-6 induced by C. albicans. FACS showed that MBL could not only bind
      to C. albicans but also bind to imDCs in a Ca2+-dependent manner. Western blot
      showed that MBL could decrease the phosphorylation of IkappaBalpha and the
      nuclear translocation of p65/ NF-kappaB. CONCLUSION: MBL may inhibit TNF-alpha
      and IL-6 production induced by C. albicans in DC through NF-kappaB signaling
      pathways, suggesting that MBL can play some roles in the regulation of C.
      albicans-induced immune response.

PMID- 25948218
TI  - [BRAF V600E Mutation in Chinese Patients with Langerhans Cell Histiocytosis and
      Its Clinical Significance].
AB  - OBJECTIVE: To investigate the BRAF V600E mutation in Chinese patients with
      langerhans cell histiocytosis (LCH) and its clinical significance. METHODS: The
      clinical records of 50 pathology-diagnosed LCH cases were analyzed
      retrospectively and the Paraffin-embedded tissue blocks were retrieved to test
      the BRAF V600E mutation by immunohistochemical method with a specific BRAF V600E
      protein antibody. BRAF V600E mutation was also tested by High-resolution Melting
      Analysis (HRM) followed by Sanger sequence in 31 cases. RESULTS: BRAF V600E
      mutation was found in 58% (29/50) LCH cases by gene test or protein test. BRAF
      V600E expression was identified in 56% (28/50) LCH cases by immunohistochemical
      analysis alone while 54.8% (17/31) by HRM-Sanger alone. Two out of 14 cases, who
      were negative for BRAF V600E by HRM-Sanger analysis, were positive by
      immunohistochemical tests (14.3%). Otherwhile, only 1 out of 17 LCH cases with a
      positive BRAF V600E mutation by gene test were negative by immunohistochemical
      analysis. The status of BRAF V600E did not show significant relevance with age,
      sex, clinical stage or response. Also, BRAF V600E had no effect on the 3-year
      survival or event-free survival in this group. CONCLUSION: Immunohistochemical
      tests for BRAF V600E in Paraffin-embedded tissue is of ideal sensitivity, 58%
      Chinese LCH patients have BRAF V600E positive and so LCH is a clonal disease but
      the exact role of BRAF V600E in LCH needs further research.

PMID- 25948219
TI  - [Characteristics of blood type irregular antibodies in Han population of Chinese
      Sichuan area].
AB  - OBJECTIVE: To analyze the distribution of irregular antibody of red blood cells
      in Han population of Chinese Sichuan area, so as to provide valuable information
      for the safety of transfusion and decrease of immune hemolytic transfusion
      reaction. METHODS: Blood samples from June 2006 to May 2013 were tested for
      irregular antibody screening and identification, calculating the composition
      rate, group characteristics and the positive detection rate of irregular
      antibody. RESULTS: A total of 36287 blood samples were tested, out of them 571
      samples were the irregular antibody positive, the positive rate was 1.574%(571/36
      287), specific alloantibodies were found in 312 samples, the positive rate was
      0.860%(312/36287). And autoantibody was found in 259 samples, the positive rate
      was 0.714%(259/36 287). The specific alloantibodies ratio in Rh system was the
      highest, reaching to 73.72%(230/312) with the positive rate of 0.634%;36 cases in
      Lewis system, account for 11.54%(36/312) with the positive rate of 0.099%; 34
      cases in MNS system account for 10.89%(34/312) with the positive rate of 0.094%;
      direct coomb test showed positive result in 284 samples, the rate was 0.78%. The
      detected rate of positive irregular antibody in female is obviously higher than
      that in male patients (P<0.001), and it is also higher in people with pregnancy
      or transfusion than that in those without it (P<0.05). CONCLUSION: The irregular
      antibody screening and identification are very important in blood transfusion,
      especially for female and people with transfusion or pregnant history.

PMID- 25948220
TI  - [Polymorphism of M, N Allele in MN Blood Group of Chinese Population].
AB  - OBJECTIVE: To detect the base sequences of all exons and part of introns in the
      GYPA gene of the glycophorin GPA and to investigate the polymorphism of M, N
      alleles in Chinese population. METHODS: A total of 225 blood sample were randomly
      colleeted from unrelated Chinese volunteers and were detected by serology
      techniques. The primers were designed by self, the seguencing of GYPA gene
      related with sample exon 1-7 full length sequences of bases and intron-1-7
      partial sequence was performed, the polymorphism of M, N gene mutation in
      mucleotide sequence was analysed. RESULTS: The results of M and N genotyping were
      in agreement with the results of serological detection. The 23rd base of intron
      2, the 55th base of intron-3, the 63rd base of intron-4, the 55th, 189th and
      190th base of intron-6, the 712th base variation of exon-7 in the gene M and N
      were used to subdivide the gene M and N into the mutant M103, M201, M202, N101,
      N102, N103, N104, and N201. At the same time, it was found that 42th and 54th
      base were mutated, the base T was inserted between 59th and 60th base in the
      intron-2, the new mutations occurred in the alleles 28, 29, 65 and 102 in intron
      3 in this study. CONCLUSION: The polymorphism of the the Chinese population's
      GYPA gene occurs in all the exons and partly in the introns. The gene
      polymorphism of M and N blood group in Chinese population might provide the
      theoretical basis for the studies of clinical blood transfusion, human population
      genetics and molecular biology.

PMID- 25948221
TI  - [Effect of Storage Time on Cumulation of Platelet-related Growth Factors in the
      Supernatant of Leukoreduced Packed Red Cells and Tumor Cell Proliferation In
      Vitro].
AB  - OBJECTIVE: To investigate the effect of storage time on accumulation of platelet
      related growth factors in the supernatant of leukoreduced packed red blood cells
      (LR-pRBC) and on tumor cell proliferation in vitro. METHODS: LR-pRBC were
      quartered and stored at 2  degrees C-6  degrees C. The supernatant of pRBC was
      obtained by centrifugation with 1 006 * g for 10 min at day 0, 14, 21 and 35 d.
      The enzyme-linked immunosorbent assay (ELISA) was used to detect the expression
      of platelet-derived growth factor(PDGF) and vascular endothelial growth factor
      (VEGF). After HepG2 cells was cultured with the supernatant of LR pRBC at day 0
      and day 35 together for 48 hours, methylthiazoliltetracolium (MTT) method was
      used to measure the proliferation of tumor cells in vitro. RESULTS: The
      concentrations of 2 cytokines were still increased with the storage time
      prolonging. As compared to LR-pRBC at day 0 [611.84 (95%CI, 356.45-867.23)
      pg/ml], the level of VEGF reached 900.16 (95% CI, 552.26-1248.07) pg/ml (P<0.05).
      There was a similar tendency in PDGF level with less increment in the supernatant
      of LR pRBC at day 35 [2.23 (95% CI, 0-5.37) ng/L vs 5.66 (95% CI, 0-12.48),
      P=0.073], but there was no significant statistical difference. Likewise, in vitro
      study of HepG2 cell proliferation showed that the LR-pRBC at day 35 promoted more
      proliferation of tumor cells with OD value 0.40 (95% CI, 0.38-0.42) (P<0.05).
      CONCLUSION: The residual platelets in LR-pRBC were activated, disintegrated and
      released the dense granules and alpha-granules which induce the accumulation of
      VEGF and PDGF. It seemed that the supernatant of LR-pRBC promoted the
      proliferation of tumor cells in vitro.

PMID- 25948222
TI  - [Comparison of thromboelastography and routine coagulation tests for evaluation
      of blood coagulation function in patients].
AB  - OBJECTIVE: To investigate the correlation and consistency between
      thromboelastography(TEG) and routine coagulation tests, and to evaluate the value
      of the two methods in determining the blood coagulation of patients. METHODS: The
      TEG, routine coagulation tests and platelet counts of 182 patients from the
      Intensive Care Unit(ICU) and Department of Gastroenterology in our hospital from
      January to September 2014 were performed and analyzed retrospectively for their
      correlation, Kappa identity test analysis and chi-square test, and the diagnostic
      sensitivity and specificity of both methods in the patients with bleeding were
      evaluated. RESULTS: The TEG R time and PT, R time and APTT showed a linear
      dependence (P<0.01). The relationship between the TEG K value, alpha-Angle, MA
      and Fibrinogen showed a linear dependence (P<0.001). And the relationship between
      the TEG K value, alpha-Angle, MA and the platelet count were in a linear
      dependent way (P<0.001). The Kappa values of the TEG R time with PT and APTT were
      0.038 (P>0.05) and 0.061 (P>0.05), respectively. The chi-square test values of
      the TEG R time with PT and APTT were 35.309 (P<0.001) and 15.848 (P<0.001),
      respectively. The Fibrinogen and the TEG K value, alpha-Angle, MA value had
      statistical significance (P<0.001), with a Kappa value of 0.323, 0.288 and 0.427,
      respectively. The chi-square test values between Fibrinogen and the TEG K value,
      alpha-Angle, MA value were not statistically significant, with X2=1.091
      (P=0.296), X2=1.361 (P=0.243), X2=0.108 (P=0.742). The Kappa values of the
      platelet count and the TEG K value, alpha-Angle, MA value were 0.379, 0.208 and
      0.352, respectively, which were also statistically significant difference
      (P<0.001). The chi-square test values between the platelet count and the TEG K
      value, alpha-Angle, MA value showed a statistically significant difference
      (P<0.001), with X2=37.5, X2=37.23, X2=26.630. The diagnostic sensitivity of the
      two methods for the patients with bleeding was less than 50%. CONCLUSION: There
      was a significant correlation between some TEG parameters and routine coagulation
      tests, but the consistency is weak. Moreover, the diagnostic sensitivity of two
      methods in the patients with bleeding is low. It was concluded that the TEG
      cannot replace the conventional coagulation tests, and the preferable method
      remains uncertain which could reflect the risk of bleeding.

PMID- 25948223
TI  - [Effect of astaxanthin on oxidative stress of red blood cells and peroxidation
      damage of membrane].
AB  - OBJECTIVE: To explore the effect of astaxanthin (ASTA) on oxidative stress of
      intra- and extra- red blood cells during stored period and the protective
      function for cell membrane. METHODS: The blood of volunteers was collected to
      prepare suspended red blood cells without leukocytes. Then the red blood cells
      were randomly divided into group A, group B, group C and group D. The ASTA was
      added into MAP preservation solution of group B, group C and group D, the final
      concentration of ASTA was 5, 10 and 20 umol/L respectively. Group A was used as
      control group, in which only the dissolved liquid DMSO of ASTA was added. The red
      blood cells were stored in refrigerator at 2  degrees C-6  degrees C. On day 7,
      14, 28 and day 42 of storage, the content of reactive oxygen species (ROS) in red
      blood cells was detected by fluorescence microplate reader. The content of
      malondialdehyde (MDA) was detected with TBA method. The content of hydrogen
      peroxide (H2O2) outside cell was detected with spectrophotometric method. The
      mean corpuscular volume(MCV) was detected with blood cell analyzer. The content
      of free hemoglobin(FHb) was detected with chemical colorimetry. RESULTS: The ROS,
      MDA, FHb and H2O2 levels in B, C and D groups were lower than those in control
      group during the stored period. On day 7 and 14 of storage, among group B, group
      C, group D and group A, the MCV showed no difference in comparison with control
      group. On day 28 and 42 of storage, the MCV in B, C and D groups was lower than
      that in control group. CONCLUSION: The ASTA can reduce the oxidative stress level
      of stored red blood cells inside and outside, relieve the peroxidation damage of
      cell membrane.

PMID- 25948224
TI  - [Research Progress on Expression Regulation, Function and Clinical Significance
      of CASP8AP2 Gene].
AB  - We systematically reviewed the results of the studies on expression regulation,
      biological functions, and clinical prognostic significance of CASP8AP2 gene. At
      present, the studies showed that the expression of CASP8AP2 gene was regulated by
      Homeobox proteins and DNA methylation, and could be silenced by miRNA-210. This
      protein was involved in apoptosis mediated by FAS and TNFalpha, NF-kappaB
      activation mediated by TNFalpha, regulation of gene expression induced by
      glucocorticoid and mineralocorticoid receptor, comprising Cajal body and histone
      locus body, transcription of replication-dependent histone, 3' end processing of
      histone, regulation of S phase progression, in addition to functioning as
      coactivator of transcription factors c-Myb and p73 to activating many genes'
      expression. On the other hand, low expression of CASP8AP2 gene was associated
      with relapse in childhood ALL. The deletion of this gene was related to the poor
      prognosis of children with T-ALL and T lymphoblastic lymphoma. Furthermore, 3
      SNPs in this gene were possibly correlated with genesis of diffuse large B cell
      lymphoma and childhood leukemia. In conclusions, CASP8AP2 was a multifunctional
      protein. It could function to regulate cell proliferation, apoptosis, and gene
      expression. In childhood hematological malignancies, CASP8AP2 was a promising
      molecular marker with prognostic significance. Some SNPs were possibly correlated
      with leukemo- and lymphomogenesis. 

PMID- 25948225
TI  - [Advances in ex vivo expansion and immunotherapy application of regulatory T
      cells].
AB  - CD4+ CD25+ regulatory T cells (Treg) play a fundamental role in the establishment
      and maintenance of immune tolerance. In a some of experimental models, it was
      found that Tregs can quench autoimmune diseases, maintain allogeneic transplants,
      and prevent allergic diseases. A major obstacle to their clinical application is
      related to their definitive phenotype and very limited number of these cells in
      peripheral circulation, no more than 5%-10% of total CD4+ T cells. Recent
      progress of technologies for Treg sorting with multicolor flow cytometry and
      immuno-absorbing columns has overcome these obstacles, and opened the doors to
      the clinical application of Treg. This review highlight the characteristics of
      Treg, describe the current information of cell sorting and ex vivo expansion
      techniques, and outline the adoptive transfer experiments and clinical trials of
      immunotherapy that have been developed in recent years. It is foreseeable that
      Treg adoptive transfusion will be a promising immunosuppressive therapy.

PMID- 25948226
TI  - [Application of Chimeric Antigen Receptor-Modified CAR-T/NK Cells to Treatment of
      Multiple Myeloma].
AB  - Chimeric antigen receptor(CAR) is a synthesized transmembrane protein, which
      redirects the modified cells through specific or associated antigen on tumor
      cells. CAR-modified T/NK cells, especially CAR-T cells, are a new tool of rapidly
      developing of adoptive immunotherapy of tumor in recent years, they give T/NK
      cells the targeting cytotoxic activity and can overcome the tumor
      immunosuppressive microenvironment and break the state of the host immune
      tolerance. CAR combines the single-chain antibody to tumor-associated antigen
      with T/NK cells' activated motifs, giving T/NK cells' tumor targeting activity,
      so enhancing their cytotoxic activity and lasting the vitality by gene
      transduction. In this article the CAR development, comparison of CAR-T and CAR-NK
      cells, surface markers on MM cells and use of CAR in MM, and CAR perspectives are
      summarized. 

PMID- 25948227
TI  - [Recent Advances of Researches on Expression, Function and Regulation of CD22].
AB  - CD22 is a type I transmembrane protein expressed on most mature B lymphocyte, and
      plays a significant role in signal transduction pathways. CD22 acts as a co
      receptor of the B-cell receptor (BCR) that inhibits the BCR signaling by antigen
      receptor interaction. The phosphorylation of CD22 can be triggered by cross
      linking of CD22 with the BCR through antigen, then predominantly triggers the
      dephosphorylation and inactivation of downstream proteins and inhibit the BCR
      signaling. Autoimmune disease could be caused by the abnormal expression or
      dysfunction of CD22 which interrupts BCR signaling and then influences the
      quantity and function of B cells. The further study of the function and
      regulation of CD22 would help us understanding the pathogenesis of autoimmune
      disease and setting theoretical basis for its targeting treatment. In this
      article, the structure and expression of CD22, the ligands of CD22, the
      regulation of BCR and transmenbrane signaling, the effect of CD22 on B cells, and
      CD22 and autoimmune diseases were reviewed. 

PMID- 25948228
TI  - [Advances in the Therapy of t(8;21) Acute Myeloid Leukemia].
AB  - The t(8;21)(q22;q22) translocation is the most common chromosomal abnormalities
      in AML, and the chromosomal translocation forms AML1-ETO. The t(8;21) AML is a
      heterogeneity disease. It is unclear for how to treat the relapsed or refractory
      AML. Recently, the clinical trials and pathogenesis have made great progress.
      This article summarizes the current clinical trials and recruiting t(8;21) AML
      clinical trials and researches that related to treatment are as followed:
      epigenetics, JAK/STAT signaling, steroid, Chinese traditional medicine, and
      interferon. With the progress of pathogenesis researches, more and more
      treatments will translate into clinical trials, which can provide more optional
      choice for relapsed or refractory t(8;21) AML. In this article the AML1-ETO
      structure and t(8;21) AML pathogenesis, the clinical researches of t(8;21) AML
      treatment and basic researches of t(8;21) AML treatment are summarized. 

PMID- 25948229
TI  - [Dual role of autophagy in chronic myeloid leukemia].
AB  - Autophagy is a lysosome-mediated self-degradation process that mediates
      degradation and recycling of all major components of eukaryotic cells to maintain
      intracellular homeostasis. Autophagy is associated with leukemo-genesis,
      treatment, drug-resistance and recurrence of chronic myeloid leukemia (CML).
      Autophagy is a double-edged sword which has dual characteristics to promote
      survival and death of CML cells. Thus exploring different roles of autophagy
      under different conditions, finding out different autophagy pathways and
      combination with autophagy inducer or inhibitor of autophagy is of great
      importance to improve therapeutic effect, overcome drug-resistance and recurrence
      and finally come to a cure. This article makes a summary on the dual role of
      autophagy in CML. 

PMID- 25948230
TI  - [Prognostic significance of cytogenetics in aged patients with acute myeloid
      leukemia].
AB  - Aged patients with acute myeloid leukemia accounted for more than half of the
      adult AML patients, which has characteristics of low complete remission rate,
      short overall survival and poor prognosis. Recently, the importance of
      cytogenetics in AML was gradually realized. The diagnosis and typing, prognosis
      stratification and guide for treatment are performed on the basis of
      cytogenetics, but the research on influence of cytogenetics on adged patients
      with AML are relatively few. This review briefly summarizes the prognostic
      significance of cytogenetics in aged patients with AML. 

PMID- 25948232
TI  - [Secondary antifungal prophylaxis in hematological malignancy patients with
      previous invasive fungal disease].
AB  - Invasive fungal disease (IFD) causes a high morbidity and mortality in patients
      with hematological malignancies. Reactivation of IFD after chemotherapy or
      hematopoietic stem cell transplantation (HSCT) is very common and associated with
      poor prognosis. Secondary antifungal prophylaxis (SAP) is effective in preventing
      IFD recurrence. With effective SAP, a history of IFD is not an absolute
      contraindication to allogeneic HSCT or continuation of high-dose chemotherapy. In
      recent years, a variety of antifungal drugs such as voriconazole, itraconazole,
      AmB and caspofungin have been found to be effective for SAP. However, its
      management during granulocytopenia and immunosuppression remains challenging.
      This review summarizes the current status of SAP in patients with hematological
      malignancies. 

PMID- 25948231
TI  - [Correlation of IKZF1 Gene with Malignant Tumors and Systemic Lupus
      Erythematosus].
AB  - IKZF1 gene located in 7p12 of chromosome, and Ikaros family zinc finger encoded
      by IKZF1, are lymphoid-restricted transcription factors. In recent years, it has
      been demonstrated that the mutation of IKZF1 gene involved in proliferation,
      metastasis and prognosis of many malignant tumor except acute lymphoblastic
      leukemia, and also involved in complex phenotypes and susceptibility to systemic
      lupus erythematosus. This review briefly introduces the molecular structure and
      physiological function of Ikaros, focusing on its function and molecular
      mechanism in proliferation, metastasis and prognosis of malignant tumors, and its
      role in the systemic lupus erythematosus. 

PMID- 25948233
TI  - [Research and Application of iPS Cells in Blood System].
AB  - Induced pluripotent stem cells (iPS cells) were first constructed by Takahshi and
      et al in 2006. They converted the mouse fibroblasts into ES-like cells via viral
      transduction with four transcription factors (Oct4, Sox2, Klf4 and c-Myc). Since,
      the significant progress has been made and many researchers have succeeded in
      inducing iPS cells from other human somatic cells by some novel approaches, such
      as combining transcriptional factors and small chemicals. IPS cells have
      significant prospect in clinical application. IPS cells derived from patient
      somatic cells can be used as a model in studying the pathogenesis of genetic
      hematological disease and applied in therapeutic screenings. Recent studies
      suggested that iPS cells can differentiate into red blood cells and platelets in
      vitro, which may make up a big blood bank for transfusion in future. In this
      review, current understanding of both recombinant technology of iPS cells and the
      research progress in hematology are summarized. 

PMID- 25948234
TI  - The effect of Pt NPs crystallinity and distribution on the photocatalytic
      activity of Pt-g-C3N4.
AB  - Loading of a co-catalyst on the surface of a semiconductor photocatalyst is often
      carried out without considering the effect of the loading procedure on the final
      product. The present study looks in detail at the effect that the loading method
      has on the morphology and final composition of platinum-based nanoparticles by
      means of XPS and TEM analysis. Additionally, reduction pre-treatments are
      performed to investigate how the coverage, crystallinity and composition of the
      NPs affect the photocatalytic H2 evolution. The activity of Pt-g-C3N4 can
      significantly be enhanced by controlling the properties of the co-catalyst NPs. 

PMID- 25948235
TI  - Evaluation of Antitumor Activity of Hesperetin-Loaded Nanoparticles Against DMBA
      Induced Oral Carcinogenesis Based on Tissue Autofluorescence Spectroscopy and
      Multivariate Analysis.
AB  - The present study is designed to understand the nature of endogenous fluorophores
      and cellular metabolism that occur in the experimental oral carcinogenesis and to
      assess their feasibility for antitumor efficacy of hesperetin-loaded
      nanoparticles (HETNPs) in comparison with native hesperetin (HET) against 7,12
      dimethyl benz(a) anthracene (DMBA)-induced oral carcinogenesis using fluorescence
      spectroscopy. The fluorescence emission spectra of the control and the
      experimental buccal mucosa are recorded at an excitation wavelength of 320 nm
      with an emission ranging from 350 to 550 nm. The results show that there is a
      reduced contribution from the emission of collagen, nicotinamide adenine
      dinucleotide (NADH) and flavin adenine dinucleotide (FAD), in DMBA-induced tumor
      tissues as compared with the control tissues. Furthermore, there was significant
      decrease in the optical redox ratio [(FAD/ (NADH + FAD)] is observed in DMBA
      induced tumor tissues, which indicates an increased metabolic activity when
      compared to the control tissues. Oral administration of HET and its
      nanoparticulates restored the status of endogenous fluorophores emission and
      would have a higher redox ratio in the buccal mucosa of DMBA painted animals.
      Taken together, the treatment of nanoparticulate hesperetin was found to be more
      effective than native hesperetin in improving the status of endogenous
      fluorophores to a near normal range in DMBA-induced hamster buccal pouch
      carcinogenesis. The results of this study raise the important possibility that
      fluorescence spectroscopy in conjunction with PC-LDA has tremendous potential for
      monitor or potentially predict response to therapy. 

PMID- 25948236
TI  - On-going collaborative priority-setting for research activity: a method of
      capacity building to reduce the research-practice translational gap.
AB  - BACKGROUND: International policy suggests that collaborative priority setting
      (CPS) between researchers and end users of research should shape the research
      agenda, and can increase capacity to address the research-practice translational
      gap. There is limited research evidence to guide how this should be done to meet
      the needs of dynamic healthcare systems. One-off priority setting events and time
      lag between decision and action prove problematic. This study illustrates the use
      of CPS in a UK research collaboration called Collaboration and Leadership in
      Applied Health Research and Care (CLAHRC). METHODS: Data were collected from a
      north of England CLAHRC through semi-structured interviews with 28 interviewees
      and a workshop of key stakeholders (n = 21) including academics, NHS clinicians,
      and managers. Documentary analysis of internal reports and CLAHRC annual reports
      for the first two and half years was also undertaken. These data were
      thematically coded. RESULTS: Methods of CPS linked to the developmental phase of
      the CLAHRC. Early methods included pre-existing historical partnerships with on
      going dialogue. Later, new platforms for on-going discussions were formed.
      Consensus techniques with staged project development were also used. All methods
      demonstrated actual or potential change in practice and services. Impact was
      enabled through the flexibility of research and implementation work streams;
      'matched' funding arrangements to support alignment of priorities in partner
      organisations; the size of the collaboration offering a resource to meet project
      needs; and the length of the programme providing stability and long term
      relationships. Difficulties included tensions between being responsive to
      priorities and the possibility of 'drift' within project work, between academics
      and practice, and between service providers and commissioners in the health
      services. Providing protected 'matched' time proved difficult for some NHS
      managers, which put increasing work pressure on them. CPS is more time consuming
      than traditional approaches to project development. CONCLUSIONS: CPS can produce
      needs-led projects that are bedded in services using a variety of methods.
      Contributing factors for effective CPS include flexibility in use and type of
      available resources, flexible work plans, and responsive leadership. The CLAHRC
      model provides a translational infrastructure that enables CPS that can impact on
      healthcare systems.

PMID- 25948237
TI  - Pancreatic cancer accompanied by a moderate-sized pseudocyst with extrapancreatic
      growth.
AB  - BACKGROUND: Pancreatic cancer accompanied by a moderate-sized pseudocyst with
      extrapancreatic growth is extremely rare. Diagnosis of pancreatic cancer on
      preoperative imaging is difficult when the pancreatic parenchyma is compressed by
      a pseudocyst and becomes unclear. Despite advances in imaging techniques,
      accurate preoperative diagnosis of cystic lesions of the pancreas remains
      difficult. In this case, it was challenging to diagnose pancreatic cancer
      preoperatively as we could not accurately assess the pancreatic parenchyma, which
      had been compressed by a moderate-sized cystic lesion with extrapancreatic
      growth. CASE PRESENTATION: A 63-year-old woman underwent investigations for
      epigastric abdominal pain. She had no history of pancreatitis. Although we
      suspected pancreatic ductal carcinoma with a pancreatic cyst, there was no mass
      lesion or low-density area suggestive of pancreatic cancer. We did not
      immediately suspect pancreatic cancer, as development of a moderate-sized cyst
      with extrapancreatic growth is extremely rare and known tumor markers were not
      elevated. Therefore, we initially suspected that a massive benign cyst (mucinous
      cyst neoplasm, serous cyst neoplasm, or intraductal papillary mucinous neoplasm)
      resulted in stenosis of the main pancreatic duct. We were unable to reach a
      definitive diagnosis prior to the operation. We had planned a
      pancreaticoduodenectomy to reach a definitive diagnosis. However, we could not
      remove the tumor because of significant invasion of the surrounding tissue
      (portal vein, superior mesenteric vein, etc.). The fluid content of the cyst was
      serous, and aspiration cytology from the pancreatic cyst was Class III (no
      malignancy), but the surrounding white connective tissue samples were positive
      for pancreatic adenocarcinoma on pathological examination during surgery. We
      repeated imaging (CT, MRI, endoscopic ultrasound, etc.) postoperatively, but
      there were neither mass lesions nor a low-density area suggestive of pancreatic
      cancer. In retrospect, we think that the slight pancreatic duct dilation was the
      only finding suggestive of pancreatic cancer. CONCLUSIONS: It is difficult to
      diagnose pancreatic cancer with pseudocyst preoperatively. If a pancreatic cyst
      is found in patients who had normal tumor marker levels or no history of
      pancreatitis, we should always consider the possibility of pancreatic cancer. In
      such cases, slight pancreatic duct dilation may be a diagnostic clue.

PMID- 25948238
TI  - Periportal fibrosis, liver and spleen sizes among S. mansoni mono or co-infected
      individuals with human immunodeficiency virus-1 in fishing villages along Lake
      Victoria shores, North-Western, Tanzania.
AB  - BACKGROUND: The pathogenesis of S. mansoni infection involves chronic
      inflammatory responses to parasite eggs which can be associated with a
      characteristic periportal fibrosis (PPF) and the progression to severe
      hepatosplenic disease. The effects of HIV-1 co-infection and the influence of
      CD4(+) cell numbers on these clinical manifestations of chronic S. mansoni are
      not known. To understand the effects of HIV-1 co-infection on these morbidities,
      we examined S. mansoni ultrasound-detectable morbidities in relation to HIV-1
      infection and CD4(+) cell counts, and other factors in fishing communities where
      the two infections are present. METHODS: Ultrasonographical examination was
      conducted during a cross-sectional study of 1,671 (aged 21-55 years) individuals
      in North-Western Tanzania. Blood samples were obtained for HIV-1 screening and
      CD4(+) cell quantification. A single stool sample was examined for S. mansoni
      eggs using the Kato-Katz technique. A questionnaire was used to collect socio
      demographic-economic information. RESULTS: The prevalence of PPF (grade C-F) was
      13.79% and 15.01% for the HIV-1 infected and non-infected individuals (P = 0.72).
      Male gender (P< 0.001), age group 21-30 years (P< 0.028) and, residential time of
      11-20 (P< 0.01) and >=21 years (P< 0.01) were associated with PPF in S. mansoni
      infected individuals. The height-adjusted measurements of the left liver lobe
      were significantly larger in HIV-1/S. mansoni co-infected compared to S. mansoni
      only-infected individuals (t = -2.0702, P< 0.039). Predictors of the height
      adjusted measurements of the left liver lobe and spleen were age, male gender,
      malaria infection, fishing occupation, village of residence and heavy intensity
      of S. mansoni infection. After accounting for these factors, neither HIV-1
      infection nor CD4(+) cell counts predicted PPF, hepatosplenomegaly, measurements
      of the liver or spleen. Height-adjusted ultrasound measurements of the left liver
      lobe did not correlate with the CD4(+) cells counts in co-infected individuals (r
      = -0.16, P = 0.084). CONCLUSION: S. mansoni-related PPF, liver and spleen
      enlargement are prevalent in the study population. The intensity of S. mansoni
      infection was associated with the enlargement of liver, spleen and
      hepatosplenomegaly. The PPF grades observed were similar in both HIV-1/S. mansoni
      co-infected and in those only infected with S. mansoni. There was no evidence
      that HIV-1 infection or CD4(+) cells counts were associated with these S. mansoni
      morbidities.

PMID- 25948240
TI  - Pain, PSA flare, and bone scan response in a patient with metastatic castration
      resistant prostate cancer treated with radium-223, a case report.
AB  - BACKGROUND: Radium-223 has been shown to improve overall survival in men with
      metastatic castration-resistant prostate cancer with symptomatic bone metastases.
      The bone scan response to radium-223 has only been described in one single center
      trial of 14 patients, none of whom achieved the outstanding bone scan response
      presented in the current case. CASE PRESENTATION: In this case report, we
      describe a 75 year-old white man with extensively pre-treated metastatic
      castration-resistant prostate cancer and symptomatic bone metastases who
      experienced a flare in pain and prostate-specific antigen, followed by dramatic
      clinical (pain), biochemical (prostate-specific antigen), and imaging (bone scan)
      response. CONCLUSION: The flare phenomena and bone scan response we observed have
      not previously been described with radium-223. This case suggests that the degree
      and duration of bone scan response may be predictive of overall survival benefit.

PMID- 25948241
TI  - Systemic right ventricular fibrosis detected by cardiovascular magnetic resonance
      is associated with clinical outcome, mainly new-onset atrial arrhythmia, in
      patients after atrial redirection surgery for transposition of the great
      arteries.
AB  - BACKGROUND: We hypothesized that fibrosis detected by late gadolinium enhancement
      (LGE) cardiovascular magnetic resonance predicts outcomes in patients with
      transposition of the great arteries post atrial redirection surgery. These
      patients have a systemic right ventricle (RV) and are at risk of arrhythmia,
      premature RV failure, and sudden death. METHODS AND RESULTS: Fifty-five patients
      (aged 27+/-7 years) underwent LGE cardiovascular magnetic resonance and were
      followed for a median 7.8 (interquartile range, 3.8-9.6) years in a prospective
      single-center cohort study. RV LGE was present in 31 (56%) patients. The
      prespecified composite clinical end point comprised new-onset sustained
      tachyarrhythmia (atrial/ventricular) or decompensated heart failure
      admission/transplantation/death. Univariate predictors of the composite end point
      (n=22 patients; 19 atrial/2 ventricular tachyarrhythmia, 1 death) included RV LGE
      presence and extent, RV volumes/mass/ejection fraction, right atrial area, peak
      Vo(2), and age at repair. In bivariate analysis, RV LGE presence was
      independently associated with the composite end point (hazard ratio, 4.95 [95%
      confidence interval, 1.60-15.28]; P=0.005), and only percent predicted peak Vo(2)
      remained significantly associated with cardiac events after controlling for RV
      LGE (hazard ratio, 0.80 [95% confidence interval, 0.68-0.95]; P=0.009/5%). In 8
      of 9 patients with >1 event, atrial tachyarrhythmia, itself a known risk factor
      for mortality, occurred first. There was agreement between location and extent of
      RV LGE at in vivo cardiovascular magnetic resonance and histologically documented
      focal RV fibrosis in an explanted heart. There was RV LGE progression in a
      different case restudied for clinical indications. CONCLUSIONS: Systemic RV LGE
      is strongly associated with adverse clinical outcome especially arrhythmia in
      transposition of the great arteries, thus LGE cardiovascular magnetic resonance
      should be incorporated in risk stratification of these patients.

PMID- 25948242
TI  - Rapid determination of eight oxoisoaporphine alkaloids in Rhizoma Menispermi by
      the optimal homogenate extraction followed by UPLC-MS/MS.
AB  - The objective of this study was to develop a rapid and reliable homogenate
      extraction (HGE) and ultra high-performance liquid chromatography-tandem mass
      spectrometric (UPLC-MS/MS) method for simultaneous analysis of eight bioactive
      oxoisoaporphine alkaloids (including two new alkaloids) in Rhizoma Menispermi.
      HGE was optimized by response surface methodology (RSM) to obtain the maximum
      extraction efficiency of eight alkaloids. Separation was achieved on a Waters
      ACQUITY UPLC(r) BEH C18 column (50 * 2.1 mm(2), 1.7 MUm) using gradient elution
      with a mobile phase consisting of acetonitrile and 0.2% formic acid in water.
      Quantification was performed with multiple reaction monitoring (MRM) mode using
      positive ESI as an interface. This is the first report of the simultaneous
      analysis of eight oxoisoaporphine alkaloids in Rhizoma Menispermi using a UPLC
      MS/MS method; this analysis afforded good linearity, precision, and accuracy.
      Then, the method was successfully applied to determine the alkaloids in Rhizoma
      Menispermi from different sources.

PMID- 25948239
TI  - Hispano-Americans in Europe: what do we know about their health status and
      determinants? A scoping review.
AB  - BACKGROUND: Policy makers and health practitioners are in need of guidance to
      respond to the growing geographic mobility of Hispano-American migrants in
      Europe. Drawing from contributions from epidemiology, social sciences,
      demography, psychology, psychiatry and economy, this scoping review provides an
      up-to-date and comprehensive synthesis of studies addressing the health status
      and determinants of this population. We describe major research gaps and suggest
      specific avenues of further inquiry. METHODS: We identified systematically papers
      that addressed the concepts "health" and "Hispano Americans" indexed in five data
      bases from Jan 1990 to May 2014 with no language restrictions. We screened the
      4,464 citations retrieved against exclusion criteria and classified 193 selected
      references in 12 thematic folders with the aid of the reference management
      software ENDNOTE X6. After reviewing the full text of all papers we extracted
      relevant data systematically into a table template to facilitate the synthesising
      process. RESULTS: Most studies focused on a particular disease, leaving
      unexplored the interlinkages between different health conditions and how these
      relate to legislative, health services, environmental, occupational, and other
      health determinants. We elucidated some consistent results but there were many
      heterogeneous findings and several popular beliefs were not fully supported by
      empirical evidence. Few studies adopted a trans-national perspective and many
      consisted of cross-sectional descriptions that considered "Hispano-Americans" as
      a homogeneous category, limiting our analysis. Our results are also constrained
      by the availability and varying quality of studies reviewed. CONCLUSIONS:
      Burgeoning research has produced some consistent findings but there are huge gaps
      in knowledge. To prevent unhelpful generalisations we need a more holistic and
      nuanced understanding of how mobility, ethnicity, income, gender, legislative
      status, employment status, working conditions, neighbourhood characteristics and
      social status intersect with demographic variables and policy contexts to
      influence the health of the diverse Hispano-American populations present in
      Europe.

PMID- 25948243
TI  - Cell-derived extracellular vesicles as a platform to identify low-invasive
      disease biomarkers.
AB  - Biomarkers are of great importance for prediction, diagnosis and monitoring the
      progression and therapeutic success of a disease. Whole body fluids, such as
      blood or urine, constitute the main desired biological source to identify these
      markers, mostly due to the minimally invasive procedures used to collect them. An
      additional benefit of studying these biological fluids that has been demonstrated
      by many different groups is that they contain cell-released extracellular
      vesicles, carrying a cargo of lipids, proteins and nucleic acids that reflects
      cell/tissue origin and, remarkably, cellular status. In this review, the
      information obtained from the characterization of this body fluid compartment in
      human samples is discussed in the context of its usefulness as diagnostic
      resource for several pathologies, including cancer, inflammatory, vascular and
      metabolic diseases. The review shows the great variety of methods used for this
      purpose as well as the different types of molecules that could serve as specific
      or common disease markers. 

PMID- 25948244
TI  - Machine learning applications in genetics and genomics.
AB  - The field of machine learning, which aims to develop computer algorithms that
      improve with experience, holds promise to enable computers to assist humans in
      the analysis of large, complex data sets. Here, we provide an overview of machine
      learning applications for the analysis of genome sequencing data sets, including
      the annotation of sequence elements and epigenetic, proteomic or metabolomic
      data. We present considerations and recurrent challenges in the application of
      supervised, semi-supervised and unsupervised machine learning methods, as well as
      of generative and discriminative modelling approaches. We provide general
      guidelines to assist in the selection of these machine learning methods and their
      practical application for the analysis of genetic and genomic data sets. 

PMID- 25948245
TI  - RNA: Putting transcriptomics in its place.

PMID- 25948247
TI  - Who needs a jackhammer when a hammer is all that may be needed?

PMID- 25948246
TI  - Haplotype-resolved genome sequencing: experimental methods and applications.
AB  - Human genomes are diploid and, for their complete description and interpretation,
      it is necessary not only to discover the variation they contain but also to
      arrange it onto chromosomal haplotypes. Although whole-genome sequencing is
      becoming increasingly routine, nearly all such individual genomes are mostly
      unresolved with respect to haplotype, particularly for rare alleles, which remain
      poorly resolved by inferential methods. Here, we review emerging technologies for
      experimentally resolving (that is, 'phasing') haplotypes across individual whole
      genome sequences. We also discuss computational methods relevant to their
      implementation, metrics for assessing their accuracy and completeness, and the
      relevance of haplotype information to applications of genome sequencing in
      research and clinical medicine. 

PMID- 25948248
TI  - Profiling gene expression in citrus fruit calyx abscission zone (AZ-C) treated
      with ethylene.
AB  - On-tree storage and harvesting of mature fruit account for a large proportion of
      cost in the production of citrus, and a reduction of the cost would not be
      achieved without a thorough understanding of the mechani sm of the mature fruit
      abscission. Genome-wide gene expression changes in ethylene-treated fruit calyx
      abscission zone (AZ-C) of Citrus sinensis cv. Olinda were therefore investigated
      using a citrus genome array representing up to 33,879 citrus transcripts. In
      total, 1313 and 1044 differentially regulated genes were identified in AZ-C
      treated with ethylene for 4 and 24 h, respectively. The results showed that
      mature citrus fruit abscission commenced with the activation of ethylene signal
      transduction pathway that led to the activation of ethylene responsive
      transcription factors and the subsequent transcriptional regulation of a large
      set of ethylene responsive genes. Significantly down-regulated genes included
      those of starch/sugar biosynthesis, transportation of water and growth promoting
      hormone synthesis and signaling, whereas significantly up-regulated genes were
      those involved in defense, cell wall degradation, and secondary metabolism. Our
      data unraveled the underlying mechanisms of some known important biochemical
      events occurring at AZ-C and should provide informative suggestions for future
      manipulation of the events to achieve a controllable abscission for mature citrus
      fruit. 

PMID- 25948249
TI  - Flow cytometric analysis of FSHR, BMRR1B, LHR and apoptosis in granulosa cells
      and ovulation rate in merino sheep.
AB  - The aim of the present study was to determine the direct cause of the mutation
      induced, increased ovulation rate in Booroola Merino (BB) sheep. Granulosa cells
      were removed from antral follicles before ovulation and post-ovulation from BB
      (n=5) and WT (n=12) Merino ewes. Direct immunofluorescence measurement of mature
      cell surface receptors using flow cytometry demonstrated a significant up
      regulation of FSH receptor (FSHR), transforming growth factor beta type 1, bone
      morphogenetic protein receptor (BMPR1B), and LH receptor (LHR) in BB sheep. The
      increased density of FSHR and LHR provide novel evidence of a mechanism for
      increasing the number of follicles that are recruited during dominant follicle
      selection. The compounding increase in receptors with increasing follicle size
      maintained the multiple follicles and reduced the apoptosis, which contributed to
      a high ovulation rate in BB sheep. In addition, we report a mutation-independent
      mechanism of down-regulation to reduce receptor density of the leading dominant
      follicle in sheep. The suppression of receptor density coincides with the
      cessation of mitogenic growth and steroidogenic differentiation as part of the
      luteinization of the follicle. The BB mutation-induced attenuation of BMPR1B
      signaling led to an increased density of the FSHR and LHR and a concurrent
      reduction in apoptosis to increase the ovulation rate. The role of BMPs in
      receptor modulation is implicated in the development of multiple ovulations. 

PMID- 25948250
TI  - Enhanced integration of motion information in children with autism.
AB  - To judge the overall direction of a shoal of fish or a crowd of people, observers
      must integrate motion signals across space and time. The limits on our ability to
      pool motion have largely been established using the motion coherence paradigm, in
      which observers report the direction of coherently moving dots amid randomly
      moving noise dots. Poor performance by autistic individuals on this task has
      widely been interpreted as evidence of disrupted integrative processes.
      Critically, however, motion coherence thresholds are not necessarily limited only
      by pooling. They could also be limited by imprecision in estimating the direction
      of individual elements or by difficulties segregating signal from noise. Here, 33
      children with autism 6-13 years of age and 33 age- and ability-matched typical
      children performed a more robust task reporting mean dot direction both in the
      presence and the absence of directional variability alongside a standard motion
      coherence task. Children with autism were just as sensitive to directional
      differences as typical children when all elements moved in the same direction (no
      variability). However, remarkably, children with autism were more sensitive to
      the average direction in the presence of directional variability, providing the
      first evidence of enhanced motion integration in autism. Despite this improved
      averaging ability, children with autism performed comparably to typical children
      in the motion coherence task, suggesting that their motion coherence thresholds
      may be limited by reduced segregation of signal from noise. Although potentially
      advantageous under some conditions, increased integration may lead to feelings of
      "sensory overload" in children with autism. 

PMID- 25948251
TI  - Upregulation of P2RX7 in Cx3cr1-Deficient Mononuclear Phagocytes Leads to
      Increased Interleukin-1beta Secretion and Photoreceptor Neurodegeneration.
AB  - Photoreceptor degeneration in age-related macular degeneration (AMD) is
      associated with an infiltration and chronic accumulation of mononuclear
      phagocytes (MPs). We have previously shown that Cx3cr1-deficient mice develop age
      and stress- related subretinal accumulation of MPs, which is associated with
      photoreceptor degeneration. Cx3cr1-deficient MPs have been shown to increase
      neuronal apoptosis through IL-1beta in neuroinflammation of the brain. The reason
      for increased IL-1beta secretion from Cx3cr1-deficient MPs, and whether IL-1beta
      is responsible for increased photoreceptor apoptosis in Cx3cr1-deficient mice,
      has not been elucidated. Here we show that Cx3cr1-deficient MPs express increased
      surface P2X7 receptor (P2RX7), which stimulates IL-1beta maturation and
      secretion. P2RX7 and IL-1beta inhibition efficiently blunted Cx3cr1-MP-dependent
      photoreceptor apoptosis in a monocyte/retina coculture system and in light
      induced subretinal inflammation of Cx3cr1-deficient mice in vivo. Our results
      provide an explanation for increased CX3CR1-dependent IL-1beta secretion and
      suggest that IL-1beta or P2RX7 inhibition can help inhibit the inflammation
      associated photoreceptor cell loss in late AMD, including geographic atrophy, for
      which no efficient treatment currently exists. 

PMID- 25948252
TI  - Faithful Representation of Tactile Intensity under Different Contexts Emerges
      from the Distinct Adaptive Properties of the First Somatosensory Relay Stations.
AB  - Adaptation allows neurons to respond to a wide range of stimulus intensities.
      However, it also leads to ambiguity as the representation of the external world
      depends on the context. We recorded neurons from Wistar rats' brainstem nuclei
      belonging to two major somatosensory pathways (lemniscal and paralemniscal) and
      explored the way in which they encode noisy stimuli under different contexts. We
      found that although their unadapted intensity-response curves are very similar,
      the adapted curves of the two pathways are distinctively different as they are
      optimized for encoding different intensity ranges. Lemniscal neurons most
      faithfully encoded stimuli when the background intensity was high, whereas
      paralemniscal cells best encoded stimuli under low intensity context.
      Intracellular recordings indicate that these differences emerge already at the
      synaptic level. We suggest that the two pathways synergistically improve the
      ability of this system to encode a wide range of intensities during natural
      stimulation, potentially reducing the inherent ambiguity of adaptive coding. 

PMID- 25948253
TI  - Rbm8a haploinsufficiency disrupts embryonic cortical development resulting in
      microcephaly.
AB  - The cerebral cortex is built during embryonic neurogenesis, a period when
      excitatory neurons are generated from progenitors. Defects in neurogenesis can
      cause acute neurodevelopmental disorders, such as microcephaly (reduced brain
      size). Altered dosage of the 1q21.1 locus has been implicated in the etiology of
      neurodevelopmental phenotypes; however, the role of 1q21.1 genes in neurogenesis
      has remained elusive. Here, we show that haploinsufficiency for Rbm8a, an exon
      junction complex (EJC) component within 1q21.1, causes severe microcephaly and
      defective neurogenesis in the mouse. At the onset of neurogenesis, Rbm8a
      regulates radial glia proliferation and prevents premature neuronal
      differentiation. Reduced Rbm8a levels result in subsequent apoptosis of neurons,
      and to a lesser extent, radial glia. Hence, compared to control, Rbm8a
      haploinsufficient brains have fewer progenitors and neurons, resulting in
      defective cortical lamination. To determine whether reciprocal dosage change of
      Rbm8a alters embryonic neurogenesis, we overexpressed human RBM8A in two animal
      models. Using in utero electroporation of mouse neocortices as well as zebrafish
      models, we find RBM8A overexpression does not significantly perturb progenitor
      number or head size. Our findings demonstrate that Rbm8a is an essential
      neurogenesis regulator, and add to a growing literature highlighting roles for
      EJC components in cortical development and neurodevelopmental pathology. Our
      results indicate that disruption of RBM8A may contribute to neurodevelopmental
      phenotypes associated with proximal 1q21.1 microdeletions. 

PMID- 25948254
TI  - Rhythmic oscillations of visual contrast sensitivity synchronized with action.
AB  - It is well known that the motor and the sensory systems structure sensory data
      collection and cooperate to achieve an efficient integration and exchange of
      information. Increasing evidence suggests that both motor and sensory functions
      are regulated by rhythmic processes reflecting alternating states of neuronal
      excitability, and these may be involved in mediating sensory-motor interactions.
      Here we show an oscillatory fluctuation in early visual processing time locked
      with the execution of voluntary action, and, crucially, even for visual stimuli
      irrelevant to the motor task. Human participants were asked to perform a reaching
      movement toward a display and judge the orientation of a Gabor patch, near
      contrast threshold, briefly presented at random times before and during the
      reaching movement. When the data are temporally aligned to the onset of movement,
      visual contrast sensitivity oscillates with periodicity within the theta band.
      Importantly, the oscillations emerge during the motor planning stage, ~500 ms
      before movement onset. We suggest that brain oscillatory dynamics may mediate an
      automatic coupling between early motor planning and early visual processing,
      possibly instrumental in linking and closing up the visual-motor control loop. 

PMID- 25948255
TI  - Audio-vocal interaction in single neurons of the monkey ventrolateral prefrontal
      cortex.
AB  - Complex audio-vocal integration systems depend on a strong interconnection
      between the auditory and the vocal motor system. To gain cognitive control over
      audio-vocal interaction during vocal motor control, the PFC needs to be involved.
      Neurons in the ventrolateral PFC (VLPFC) have been shown to separately encode the
      sensory perceptions and motor production of vocalizations. It is unknown,
      however, whether single neurons in the PFC reflect audio-vocal interactions. We
      therefore recorded single-unit activity in the VLPFC of rhesus monkeys (Macaca
      mulatta) while they produced vocalizations on command or passively listened to
      monkey calls. We found that 12% of randomly selected neurons in VLPFC modulated
      their discharge rate in response to acoustic stimulation with species-specific
      calls. Almost three-fourths of these auditory neurons showed an additional
      modulation of their discharge rates either before and/or during the monkeys'
      motor production of vocalization. Based on these audio-vocal interactions, the
      VLPFC might be well positioned to combine higher order auditory processing with
      cognitive control of the vocal motor output. Such audio-vocal integration
      processes in the VLPFC might constitute a precursor for the evolution of complex
      learned audio-vocal integration systems, ultimately giving rise to human speech. 

PMID- 25948256
TI  - Distinct brainstem and forebrain circuits receiving tracheal sensory neuron
      inputs revealed using a novel conditional anterograde transsynaptic viral tracing
      system.
AB  - Sensory nerves innervating the mucosa of the airways monitor the local
      environment for the presence of irritant stimuli and, when activated, provide
      input to the nucleus of the solitary tract (Sol) and paratrigeminal nucleus (Pa5)
      in the medulla to drive a variety of protective behaviors. Accompanying these
      behaviors are perceivable sensations that, particularly for stimuli in the
      proximal end of the airways, can be discrete and localizable. Airway sensations
      likely reflect the ascending airway sensory circuitry relayed via the Sol and
      Pa5, which terminates broadly throughout the CNS. However, the relative
      contribution of the Sol and Pa5 to these ascending pathways is not known. In the
      present study, we developed and characterized a novel conditional anterograde
      transneuronal viral tracing system based on the H129 strain of herpes simplex
      virus 1 and used this system in rats along with conventional neuroanatomical
      tracing with cholera toxin B to identify subcircuits in the brainstem and
      forebrain that are in receipt of relayed airway sensory inputs via the Sol and
      Pa5. We show that both the Pa5 and proximal airways disproportionately receive
      afferent terminals arising from the jugular (rather than nodose) vagal ganglia
      and the output of the Pa5 is predominately directed toward the ventrobasal
      thalamus. We propose the existence of a somatosensory-like pathway from the
      proximal airways involving jugular ganglia afferents, the Pa5, and the
      somatosensory thalamus and suggest that this pathway forms the anatomical
      framework for sensations arising from the proximal airway mucosa. 

PMID- 25948257
TI  - Neuronal morphology generates high-frequency firing resonance.
AB  - The attenuation of neuronal voltage responses to high-frequency current inputs by
      the membrane capacitance is believed to limit single-cell bandwidth. However,
      neuronal populations subject to stochastic fluctuations can follow inputs beyond
      this limit. We investigated this apparent paradox theoretically and
      experimentally using Purkinje cells in the cerebellum, a motor structure that
      benefits from rapid information transfer. We analyzed the modulation of firing in
      response to the somatic injection of sinusoidal currents. Computational modeling
      suggested that, instead of decreasing with frequency, modulation amplitude can
      increase up to high frequencies because of cellular morphology.
      Electrophysiological measurements in adult rat slices confirmed this prediction
      and displayed a marked resonance at 200 Hz. We elucidated the underlying
      mechanism, showing that the two-compartment morphology of the Purkinje cell,
      interacting with a simple spiking mechanism and dendritic fluctuations, is
      sufficient to create high-frequency signal amplification. This mechanism, which
      we term morphology-induced resonance, is selective for somatic inputs, which in
      the Purkinje cell are exclusively inhibitory. The resonance sensitizes Purkinje
      cells in the frequency range of population oscillations observed in vivo. 

PMID- 25948258
TI  - Intelligent information loss: the coding of facial identity, head pose, and non
      face information in the macaque face patch system.
AB  - Faces are a behaviorally important class of visual stimuli for primates. Recent
      work in macaque monkeys has identified six discrete face areas where most neurons
      have higher firing rates to images of faces compared with other objects (Tsao et
      al., 2006). While neurons in these areas appear to have different tuning
      (Freiwald and Tsao, 2010; Issa and DiCarlo, 2012), exactly what types of
      information and, consequently, which visual behaviors neural populations within
      each face area can support, is unknown. Here we use population decoding to better
      characterize three of these face patches (ML/MF, AL, and AM). We show that neural
      activity in all patches contains information that discriminates between the broad
      categories of face and nonface objects, individual faces, and nonface stimuli.
      Information is present in both high and lower firing rate regimes. However, there
      were significant differences between the patches, with the most anterior patch
      showing relatively weaker representation of nonface stimuli. Additionally, we
      find that pose-invariant face identity information increases as one moves to more
      anterior patches, while information about the orientation of the head decreases.
      Finally, we show that all the information we can extract from the population is
      present in patterns of activity across neurons, and there is relatively little
      information in the total activity of the population. These findings give new
      insight into the representations constructed by the face patch system and how
      they are successively transformed. 

PMID- 25948259
TI  - BK Channels Localize to the Paranodal Junction and Regulate Action Potentials in
      Myelinated Axons of Cerebellar Purkinje Cells.
AB  - In myelinated axons, K(+) channels are clustered in distinct membrane domains to
      regulate action potentials (APs). At nodes of Ranvier, Kv7 channels are expressed
      with Na(+) channels, whereas Kv1 channels flank nodes at juxtaparanodes.
      Regulation of axonal APs by K(+) channels would be particularly important in fast
      spiking projection neurons such as cerebellar Purkinje cells. Here, we show that
      BK/Slo1 channels are clustered at the paranodal junctions of myelinated Purkinje
      cell axons of rat and mouse. The paranodal junction is formed by a set of cell
      adhesion molecules, including Caspr, between the node and juxtaparanodes in which
      it separates nodal from internodal membrane domains. Remarkably, only Purkinje
      cell axons have detectable paranodal BK channels, whose clustering requires the
      formation of the paranodal junction via Caspr. Thus, BK channels occupy this
      unique domain in Purkinje cell axons along with the other K(+) channel complexes
      at nodes and juxtaparanodes. To investigate the physiological role of novel
      paranodal BK channels, we examined the effect of BK channel blockers on
      antidromic AP conduction. We found that local application of blockers to the axon
      resulted in a significant increase in antidromic AP failure at frequencies above
      100 Hz. We also found that Ni(2+) elicited a similar effect on APs, indicating
      the involvement of Ni(2+)-sensitive Ca(2+) channels. Furthermore, axonal
      application of BK channel blockers decreased the inhibitory synaptic response in
      the deep cerebellar nuclei. Thus, paranodal BK channels uniquely support high
      fidelity firing of APs in myelinated Purkinje cell axons, thereby underpinning
      the output of the cerebellar cortex. 

PMID- 25948261
TI  - Changes in Nicotinic Neurotransmission during Enteric Nervous System Development.
AB  - Acetylcholine-activating pentameric nicotinic receptors (nAChRs) are an essential
      mode of neurotransmission in the enteric nervous system (ENS). In this study, we
      examined the functional development of specific nAChR subtypes in myenteric
      neurons using Wnt1-Cre;R26R-GCaMP3 mice, where all enteric neurons and glia
      express the genetically encoded calcium indicator, GCaMP3. Transcripts encoding
      alpha3, alpha4, alpha7, beta2, and beta4 nAChR subunits were already expressed at
      low levels in the E11.5 gut and by E14.5 and, thereafter, alpha3 and beta4
      transcripts were the most abundant. The effect of specific nAChR subtype
      antagonists on evoked calcium activity in enteric neurons was investigated at
      different ages. Blockade of the alpha3beta4 receptors reduced electrically and
      chemically evoked calcium responses at E12.5, E14.5, and P0. In addition to the
      alpha3beta4 antagonist, antagonists to alpha3beta2 and alpha4beta2 also
      significantly reduced responses by P10-11 and in adult preparations. Therefore,
      there is an increase in the diversity of functional nAChRs during postnatal
      development. However, an alpha7 nAChR antagonist had no effect at any age.
      Furthermore, at E12.5 we found evidence for unconventional receptors that were
      responsive to the nAChR agonists 1-dimethyl-4-phenylpiperazinium and nicotine,
      but were insensitive to the general nicotinic blocker, hexamethonium. Migration,
      differentiation, and neuritogenesis assays did not reveal a role for nAChRs in
      these processes during embryonic development. In conclusion, there are
      significant changes in the contribution of different nAChR subunits to synaptic
      transmission during ENS development, even after birth. This is the first study to
      investigate the development of cholinergic transmission in the ENS. 

PMID- 25948260
TI  - Unilateral prefrontal lesions impair memory-guided comparisons of contralateral
      visual motion.
AB  - The contribution of the lateral prefrontal cortex (LPFC) to working memory is the
      topic of active debate. On the one hand, it has been argued that the persistent
      delay activity in LPFC recorded during some working memory tasks is a reflection
      of sensory storage, the notion supported by some lesion studies. On the other
      hand, there is emerging evidence that the LPFC plays a key role in the
      maintenance of sensory information not by storing relevant visual signals but by
      allocating visual attention to such stimuli. In this study, we addressed this
      question by examining the effects of unilateral LPFC lesions during a working
      memory task requiring monkeys to compare directions of two moving stimuli,
      separated by a delay. The lesions resulted in impaired thresholds for
      contralesional stimuli at longer delays, and these deficits were most dramatic
      when the task required rapid reallocation of spatial attention. In addition,
      these effects were equally pronounced when the remembered stimuli were at
      threshold or moved coherently. The contralesional nature of the deficits points
      to the importance of the interactions between the LPFC and the motion processing
      neurons residing in extrastriate area MT. Delay-specificity of the deficit
      supports LPFC involvement in the maintenance stage of the comparison task.
      However, because this deficit was independent of stimulus features giving rise to
      the remembered direction and was most pronounced during rapid shifts of
      attention, its role is more likely to be attending and accessing the preserved
      motion signals rather than their storage. 

PMID- 25948262
TI  - Single-Molecule Imaging of PSD-95 mRNA Translation in Dendrites and Its
      Dysregulation in a Mouse Model of Fragile X Syndrome.
AB  - Fragile X syndrome (FXS) is caused by the loss of the fragile X mental
      retardation protein (FMRP), an RNA binding protein that regulates translation of
      numerous target mRNAs, some of which are dendritically localized. Our previous
      biochemical studies using synaptoneurosomes demonstrate a role for FMRP and miR
      125a in regulating the translation of PSD-95 mRNA. However, the local translation
      of PSD-95 mRNA within dendrites and spines, as well as the roles of FMRP or miR
      125a, have not been directly studied. Herein, local synthesis of a Venus-PSD-95
      fusion protein was directly visualized in dendrites and spines using single
      molecule imaging of a diffusion-restricted Venus-PSD-95 reporter under control of
      the PSD-95 3'UTR. The basal translation rates of Venus-PSD-95 mRNA was increased
      in cultured hippocampal neurons from Fmr1 KO mice compared with WT neurons, which
      correlated with a transient elevation of endogenous PSD-95 within dendrites.
      Following mGluR stimulation with (S)-3,5-dihydroxyphenylglycine, the rate of
      Venus-PSD-95 mRNA translation increased rapidly in dendrites of WT hippocampal
      neurons, but not in those of Fmr1 KO neurons or when the binding site of miR125a,
      previously shown to bind PSD-95 3'UTR, was mutated. This study provides direct
      support for the hypothesis that local translation within dendrites and spines is
      dysregulated in FXS. Impairments in the regulated local synthesis of PSD-95, a
      critical regulator of synaptic structure and function, may affect the
      spatiotemporal control of PSD-95 levels and affect dendritic spine development
      and synaptic plasticity in FXS. 

PMID- 25948263
TI  - GIRK Channels Modulate Opioid-Induced Motor Activity in a Cell Type- and Subunit
      Dependent Manner.
AB  - G-protein-gated inwardly rectifying K(+) (GIRK/Kir3) channel activation underlies
      key physiological effects of opioids, including analgesia and dependence. GIRK
      channel activation has also been implicated in the opioid-induced inhibition of
      midbrain GABA neurons and consequent disinhibition of dopamine (DA) neurons in
      the ventral tegmental area (VTA). Drug-induced disinhibition of VTA DA neurons
      has been linked to reward-related behaviors and underlies opioid-induced motor
      activation. Here, we demonstrate that mouse VTA GABA neurons express a GIRK
      channel formed by GIRK1 and GIRK2 subunits. Nevertheless, neither constitutive
      genetic ablation of Girk1 or Girk2, nor the selective ablation of GIRK channels
      in GABA neurons, diminished morphine-induced motor activity in mice. Moreover,
      direct activation of GIRK channels in midbrain GABA neurons did not enhance motor
      activity. In contrast, genetic manipulations that selectively enhanced or
      suppressed GIRK channel function in midbrain DA neurons correlated with decreased
      and increased sensitivity, respectively, to the motor-stimulatory effect of
      systemic morphine. Collectively, these data support the contention that the
      unique GIRK channel subtype in VTA DA neurons, the GIRK2/GIRK3 heteromer,
      regulates the sensitivity of the mouse mesolimbic DA system to drugs with
      addictive potential. 

PMID- 25948264
TI  - Assessment at the single-cell level identifies neuronal glutathione depletion as
      both a cause and effect of ischemia-reperfusion oxidative stress.
AB  - Oxidative stress contributes to neuronal death in brain ischemia-reperfusion.
      Tissue levels of the endogenous antioxidant glutathione (GSH) are depleted during
      ischemia-reperfusion, but it is unknown whether this depletion is a cause or an
      effect of oxidative stress, and whether it occurs in neurons or other cell types.
      We used immunohistochemical methods to evaluate glutathione, superoxide, and
      oxidative stress in mouse hippocampal neurons after transient forebrain ischemia.
      GSH levels in CA1 pyramidal neurons were normally high relative to surrounding
      neuropil, and exhibited a time-dependent decrease during the first few hours of
      reperfusion. Colabeling for superoxide in the neurons showed a concurrent
      increase in detectable superoxide over this interval. To identify cause-effect
      relationships between these changes, we independently manipulated superoxide
      production and GSH metabolism during reperfusion. Mice in which NADPH oxidase
      activity was blocked to prevent superoxide production showed preservation of
      neuronal GSH content, thus demonstrating that neuronal GSH depletion is result of
      oxidative stress. Conversely, mice in which neuronal GSH levels were maintained
      by N-acetyl cysteine treatment during reperfusion showed less neuronal superoxide
      signal, oxidative stress, and neuronal death. At 3 d following ischemia, GSH
      content in reactive astrocytes and microglia was increased in the hippocampal CA1
      relative to surviving neurons. Results of these studies demonstrate that neuronal
      GSH depletion is both a result and a cause of neuronal oxidative stress after
      ischemia-reperfusion, and that postischemic restoration of neuronal GSH levels
      can be neuroprotective. 

PMID- 25948265
TI  - NGL-2 Is a New Partner of PAR Complex in Axon Differentiation.
AB  - Neuronal polarization is pivotal for neural network formation during brain
      development. Axon differentiation is a hallmark of initial neuronal polarization.
      Here, we report that the leucine-rich repeat-containing protein netrin-G ligand-2
      (NGL-2) as a polarity regulator that localizes asymmetrically in rat hippocampal
      neurons and is required for differentiation of the future axon. NGL-2 was
      associated with PAR complex, and this interaction resulted in local stabilization
      of axonal microtubules. Further study showed that the C terminal of NGL-2 binds
      to the PDZ domain of PAR6, and NGL-2 interacts with PAR3 and atypical PKCzeta
      (aPKCzeta), with PAR6 acting as a bridge or modifier. Then, NGL-2 regulates the
      local stabilization of microtubules and promotes axon differentiation by the
      aPKCzeta/microtubule affinity-regulating kinase 2 pathway. These findings reveal
      the critical role of NGL-2 in regulating axon differentiation in rat hippocampal
      neurons and reveal a novel partner of the PAR complex. 

PMID- 25948266
TI  - Neural basis of identity information extraction from noisy face images.
AB  - Previous research has made significant progress in identifying the neural basis
      of the remarkably efficient and seemingly effortless face perception in humans.
      However, the neural processes that enable the extraction of facial information
      under challenging conditions when face images are noisy and deteriorated remains
      poorly understood. Here we investigated the neural processes underlying the
      extraction of identity information from noisy face images using fMRI. For each
      participant, we measured (1) face-identity discrimination performance outside the
      scanner, (2) visual cortical fMRI responses for intact and phase-randomized face
      stimuli, and (3) intrinsic functional connectivity using resting-state fMRI. Our
      whole-brain analysis showed that the presence of noise led to reduced and
      increased fMRI responses in the mid-fusiform gyrus and the lateral occipital
      cortex, respectively. Furthermore, the noise-induced modulation of the fMRI
      responses in the right face-selective fusiform face area (FFA) was closely
      associated with individual differences in the identity discrimination performance
      of noisy faces: smaller decrease of the fMRI responses was accompanied by better
      identity discrimination. The results also revealed that the strength of the
      intrinsic functional connectivity within the visual cortical network composed of
      bilateral FFA and bilateral object-selective lateral occipital cortex (LOC)
      predicted the participants' ability to discriminate the identity of noisy face
      images. These results imply that perception of facial identity in the case of
      noisy face images is subserved by neural computations within the right FFA as
      well as a re-entrant processing loop involving bilateral FFA and LOC. 

PMID- 25948267
TI  - Trunk robot rehabilitation training with active stepping reorganizes and enriches
      trunk motor cortex representations in spinal transected rats.
AB  - Trunk motor control is crucial for postural stability and propulsion after low
      thoracic spinal cord injury (SCI) in animals and humans. Robotic rehabilitation
      aimed at trunk shows promise in SCI animal models and patients. However, little
      is known about the effect of SCI and robot rehabilitation of trunk on cortical
      motor representations. We previously showed reorganization of trunk motor cortex
      after adult SCI. Non-stepping training also exacerbated some SCI-driven plastic
      changes. Here we examine effects of robot rehabilitation that promotes recovery
      of hindlimb weight support functions on trunk motor cortex representations. Adult
      rats spinal transected as neonates (NTX rats) at the T9/10 level significantly
      improve function with our robot rehabilitation paradigm, whereas treadmill-only
      trained do not. We used intracortical microstimulation to map motor cortex in two
      NTX groups: (1) treadmill trained (control group); and (2) robot-assisted
      treadmill trained (improved function group). We found significant robot
      rehabilitation-driven changes in motor cortex: (1) caudal trunk motor areas
      expanded; (2) trunk coactivation at cortex sites increased; (3) richness of trunk
      cortex motor representations, as examined by cumulative entropy and mutual
      information for different trunk representations, increased; (4) trunk motor
      representations in the cortex moved toward more normal topography; and (5) trunk
      and forelimb motor representations that SCI-driven plasticity and compensations
      had caused to overlap were segregated. We conclude that effective robot
      rehabilitation training induces significant reorganization of trunk motor cortex
      and partially reverses some plastic changes that may be adaptive in non-stepping
      paraplegia after SCI. 

PMID- 25948268
TI  - Bex3 Dimerization Regulates NGF-Dependent Neuronal Survival and Differentiation
      by Enhancing trkA Gene Transcription.
AB  - The development of the nervous system is a temporally and spatially coordinated
      process that relies on the proper regulation of the genes involved. Neurotrophins
      and their receptors are directly responsible for the survival and differentiation
      of sensory and sympathetic neurons; however, it is not fully understood how genes
      encoding Trk neurotrophin receptors are regulated. Here, we show that rat Bex3
      protein specifically regulates TrkA expression by acting at the trkA gene
      promoter level. Bex3 dimerization and shuttling to the nucleus regulate the
      transcription of the trkA promoter under basal conditions and also enhance nerve
      growth factor (NGF)-mediated trkA promoter activation. Moreover, qChIP assays
      indicate that Bex3 associates with the trkA promoter within a 150 bp sequence,
      immediately upstream from the transcription start site, which is sufficient to
      mediate the effects of Bex3. Consequently, the downregulation of Bex3 using shRNA
      increases neuronal apoptosis in NGF-dependent sensory neurons deprived of NGF and
      compromises PC12 cell differentiation in response to NGF. Our results support an
      important role for Bex3 in the regulation of TrkA expression and in NGF-mediated
      functions through modulation of the trkA promoter. 

PMID- 25948269
TI  - Dynamic encoding of speech sequence probability in human temporal cortex.
AB  - Sensory processing involves identification of stimulus features, but also
      integration with the surrounding sensory and cognitive context. Previous work in
      animals and humans has shown fine-scale sensitivity to context in the form of
      learned knowledge about the statistics of the sensory environment, including
      relative probabilities of discrete units in a stream of sequential auditory
      input. These statistics are a defining characteristic of one of the most
      important sequential signals humans encounter: speech. For speech, extensive
      exposure to a language tunes listeners to the statistics of sound sequences. To
      address how speech sequence statistics are neurally encoded, we used high
      resolution direct cortical recordings from human lateral superior temporal cortex
      as subjects listened to words and nonwords with varying transition probabilities
      between sound segments. In addition to their sensitivity to acoustic features
      (including contextual features, such as coarticulation), we found that neural
      responses dynamically encoded the language-level probability of both preceding
      and upcoming speech sounds. Transition probability first negatively modulated
      neural responses, followed by positive modulation of neural responses, consistent
      with coordinated predictive and retrospective recognition processes,
      respectively. Furthermore, transition probability encoding was different for real
      English words compared with nonwords, providing evidence for online interactions
      with high-order linguistic knowledge. These results demonstrate that sensory
      processing of deeply learned stimuli involves integrating physical stimulus
      features with their contextual sequential structure. Despite not being
      consciously aware of phoneme sequence statistics, listeners use this information
      to process spoken input and to link low-level acoustic representations with
      linguistic information about word identity and meaning. 

PMID- 25948271
TI  - Longitudinal changes in adolescent risk-taking: a comprehensive study of neural
      responses to rewards, pubertal development, and risk-taking behavior.
AB  - Prior studies have highlighted adolescence as a period of increased risk-taking,
      which is postulated to result from an overactive reward system in the brain.
      Longitudinal studies are pivotal for testing these brain-behavior relations
      because individual slopes are more sensitive for detecting change. The aim of the
      current study was twofold: (1) to test patterns of age-related change (i.e.,
      linear, quadratic, and cubic) in activity in the nucleus accumbens, a key reward
      region in the brain, in relation to change in puberty (self-report and
      testosterone levels), laboratory risk-taking and self-reported risk-taking
      tendency; and (2) to test whether individual differences in pubertal development
      and risk-taking behavior were contributors to longitudinal change in nucleus
      accumbens activity. We included 299 human participants at the first time point
      and 254 participants at the second time point, ranging between ages 8-27 years,
      time points were separated by a 2 year interval. Neural responses to rewards,
      pubertal development (self-report and testosterone levels), laboratory risk
      taking (balloon analog risk task; BART), and self-reported risk-taking tendency
      (Behavior Inhibition System/Behavior Activation System questionnaire) were
      collected at both time points. The longitudinal analyses confirmed the quadratic
      age pattern for nucleus accumbens activity to rewards (peaking in adolescence),
      and the same quadratic pattern was found for laboratory risk-taking (BART).
      Nucleus accumbens activity change was further related to change in testosterone
      and self-reported reward-sensitivity (BAS Drive). Thus, this longitudinal
      analysis provides new insight in risk-taking and reward sensitivity in
      adolescence: (1) confirming an adolescent peak in nucleus accumbens activity, and
      (2) underlining a critical role for pubertal hormones and individual differences
      in risk-taking tendency. 

PMID- 25948270
TI  - Drug predictive cues activate aversion-sensitive striatal neurons that encode
      drug seeking.
AB  - Drug-associated cues have profound effects on an addict's emotional state and
      drug-seeking behavior. Although this influence must involve the motivational
      neural system that initiates and encodes the drug-seeking act, surprisingly
      little is known about the nature of such physiological events and their
      motivational consequences. Three experiments investigated the effect of a cocaine
      predictive stimulus on dopamine signaling, neuronal activity, and reinstatement
      of cocaine seeking. In all experiments, rats were divided into two groups (paired
      and unpaired), and trained to self-administer cocaine in the presence of a tone
      that signaled the immediate availability of the drug. For rats in the paired
      group, self-administration sessions were preceded by a taste cue that signaled
      delayed drug availability. Assessments of hedonic responses indicated that this
      delay cue became aversive during training. Both the self-administration behavior
      and the immediate cue were subsequently extinguished in the absence of cocaine.
      After extinction of self-administration behavior, the presentation of the
      aversive delay cue reinstated drug seeking. In vivo electrophysiology and
      voltammetry recordings in the nucleus accumbens measured the neural responses to
      both the delay and immediate drug cues after extinction. Interestingly, the
      presentation of the delay cue simultaneously decreased dopamine signaling and
      increased excitatory encoding of the immediate cue. Most importantly, the delay
      cue selectively enhanced the baseline activity of neurons that would later encode
      drug seeking. Together these observations reveal how cocaine cues can modulate
      not only affective state, but also the neurochemical and downstream
      neurophysiological environment of striatal circuits in a manner that promotes
      drug seeking. 

PMID- 25948273
TI  - Evidence for Neural Computations of Temporal Coherence in an Auditory Scene and
      Their Enhancement during Active Listening.
AB  - The human brain has evolved to operate effectively in highly complex acoustic
      environments, segregating multiple sound sources into perceptually distinct
      auditory objects. A recent theory seeks to explain this ability by arguing that
      stream segregation occurs primarily due to the temporal coherence of the neural
      populations that encode the various features of an individual acoustic source.
      This theory has received support from both psychoacoustic and functional magnetic
      resonance imaging (fMRI) studies that use stimuli which model complex acoustic
      environments. Termed stochastic figure-ground (SFG) stimuli, they are composed of
      a "figure" and background that overlap in spectrotemporal space, such that the
      only way to segregate the figure is by computing the coherence of its frequency
      components over time. Here, we extend these psychoacoustic and fMRI findings by
      using the greater temporal resolution of electroencephalography to investigate
      the neural computation of temporal coherence. We present subjects with modified
      SFG stimuli wherein the temporal coherence of the figure is modulated
      stochastically over time, which allows us to use linear regression methods to
      extract a signature of the neural processing of this temporal coherence. We do
      this under both active and passive listening conditions. Our findings show an
      early effect of coherence during passive listening, lasting from ~115 to 185 ms
      post-stimulus. When subjects are actively listening to the stimuli, these
      responses are larger and last longer, up to ~265 ms. These findings provide
      evidence for early and preattentive neural computations of temporal coherence
      that are enhanced by active analysis of an auditory scene. 

PMID- 25948272
TI  - Modulating conscious movement intention by noninvasive brain stimulation and the
      underlying neural mechanisms.
AB  - Conscious intention is a fundamental aspect of the human experience. Despite long
      standing interest in the basis and implications of intention, its underlying
      neurobiological mechanisms remain poorly understood. Using high-definition
      transcranial DC stimulation (tDCS), we observed that enhancing spontaneous
      neuronal excitability in both the angular gyrus and the primary motor cortex
      caused the reported time of conscious movement intention to be ~60-70 ms earlier.
      Slow brain waves recorded ~2-3 s before movement onset, as well as hundreds of
      milliseconds after movement onset, independently correlated with the modulation
      of conscious intention by brain stimulation. These brain activities together
      accounted for 81% of interindividual variability in the modulation of movement
      intention by brain stimulation. A computational model using coupled leaky
      integrator units with biophysically plausible assumptions about the effect of
      tDCS captured the effects of stimulation on both neural activity and behavior.
      These results reveal a temporally extended brain process underlying conscious
      movement intention that spans seconds around movement commencement. 

PMID- 25948274
TI  - Endogenous opioid activity in the anterior cingulate cortex is required for
      relief of pain.
AB  - Pain is aversive, and its relief elicits reward mediated by dopaminergic
      signaling in the nucleus accumbens (NAc), a part of the mesolimbic reward
      motivation pathway. How the reward pathway is engaged by pain-relieving
      treatments is not known. Endogenous opioid signaling in the anterior cingulate
      cortex (ACC), an area encoding pain aversiveness, contributes to pain modulation.
      We examined whether endogenous ACC opioid neurotransmission is required for
      relief of pain and subsequent downstream activation of NAc dopamine signaling.
      Conditioned place preference (CPP) and in vivo microdialysis were used to assess
      negative reinforcement and NAc dopaminergic transmission. In rats with
      postsurgical or neuropathic pain, blockade of opioid signaling in the rostral ACC
      (rACC) inhibited CPP and NAc dopamine release resulting from non-opioid pain
      relieving treatments, including peripheral nerve block or spinal clonidine, an
      alpha2-adrenergic agonist. Conversely, pharmacological activation of rACC opioid
      receptors of injured, but not pain-free, animals was sufficient to stimulate
      dopamine release in the NAc and produce CPP. In neuropathic, but not sham
      operated, rats, systemic doses of morphine that did not affect withdrawal
      thresholds elicited CPP and NAc dopamine release, effects that were prevented by
      blockade of ACC opioid receptors. The data provide a neural explanation for the
      preferential effects of opioids on pain affect and demonstrate that engagement of
      NAc dopaminergic transmission by non-opioid pain-relieving treatments depends on
      upstream ACC opioid circuits. Endogenous opioid signaling in the ACC appears to
      be both necessary and sufficient for relief of pain aversiveness. 

PMID- 25948275
TI  - Myelin loss and axonal ion channel adaptations associated with gray matter
      neuronal hyperexcitability.
AB  - Myelination and voltage-gated ion channel clustering at the nodes of Ranvier are
      essential for the rapid saltatory conduction of action potentials. Whether
      myelination influences the structural organization of the axon initial segment
      (AIS) and action potential initiation is poorly understood. Using the cuprizone
      mouse model, we combined electrophysiological recordings with immunofluorescence
      of the voltage-gated Nav1.6 and Kv7.3 subunits and anchoring proteins to analyze
      the functional and structural properties of single demyelinated neocortical L5
      axons. Whole-cell recordings demonstrated that neurons with demyelinated axons
      were intrinsically more excitable, characterized by increased spontaneous
      suprathreshold depolarizations as well as antidromically propagating action
      potentials ectopically generated in distal parts of the axon. Immunofluorescence
      examination of demyelinated axons showed that betaIV-spectrin, Nav1.6, and the
      Kv7.3 channels in nodes of Ranvier either dissolved or extended into the
      paranodal domains. In contrast, while the AIS in demyelinated axons started more
      closely to the soma, ankyrin G, betaIV-spectrin, and the ion channel expression
      were maintained. Structure-function analysis and computational modeling,
      constrained by the AIS location and realistic dendritic and axonal morphologies,
      confirmed that a more proximal onset of the AIS slightly reduced the efficacy of
      action potential generation, suggesting a compensatory role. These results
      suggest that oligodendroglial myelination is not only important for maximizing
      conduction velocity, but also for limiting hyperexcitability of pyramidal
      neurons. 

PMID- 25948276
TI  - Layer 4 pyramidal neurons exhibit robust dendritic spine plasticity in vivo after
      input deprivation.
AB  - Pyramidal neurons in layers 2/3 and 5 of primary somatosensory cortex (S1)
      exhibit somewhat modest synaptic plasticity after whisker input deprivation.
      Whether neurons involved at earlier steps of sensory processing show more or less
      plasticity has not yet been examined. Here, we used longitudinal in vivo two
      photon microscopy to investigate dendritic spine dynamics in apical tufts of GFP
      expressing layer 4 (L4) pyramidal neurons of the vibrissal (barrel) S1 after
      unilateral whisker trimming. First, we characterize the molecular, anatomical,
      and electrophysiological properties of identified L4 neurons in Ebf2-Cre
      transgenic mice. Next, we show that input deprivation results in a substantial
      (~50%) increase in the rate of dendritic spine loss, acutely (4-8 d) after
      whisker trimming. This robust synaptic plasticity in L4 suggests that primary
      thalamic recipient pyramidal neurons in S1 may be particularly sensitive to
      changes in sensory experience. Ebf2-Cre mice thus provide a useful tool for
      future assessment of initial steps of sensory processing in S1. 

PMID- 25948277
TI  - Orexin Signaling in the VTA Gates Morphine-Induced Synaptic Plasticity.
AB  - Dopamine neurons in the ventral tegmental area (VTA) are a key target of
      addictive drugs, and neuroplasticity in this region may underlie some of the core
      features of addiction. From the very first exposure, all drugs of abuse induce
      synaptic plasticity in the VTA. However, it is not well understood how this
      diverse group of drugs brings about common synaptic change. Orexin (also known as
      hypocretin) is a lateral hypothalamic neuropeptide released into the VTA that
      promotes drug-seeking behaviors and potentiates excitatory synaptic transmission
      onto VTA dopamine neurons. Here we show that signaling at orexin receptor type 1
      (OxR1) in the VTA is required for morphine-induced plasticity of dopamine
      neurons. Systemic or intra-VTA administration of the OxR1 antagonist SB 334867 in
      rats blocked a morphine-induced increase in the AMPAR/NMDAR ratio, an increase in
      presynaptic glutamate release, and a postsynaptic change in AMPAR number or
      function, including a switch in subunit composition. Furthermore, SB 334867
      blocked a morphine-induced decrease in presynaptic GABA release, and a morphine
      induced shift in the balance of excitatory and inhibitory synaptic inputs to
      dopamine neurons. These findings identify a novel role for orexin in morphine
      induced plasticity in the VTA and provide a mechanism by which orexin can gate
      the output of dopamine neurons. 

PMID- 25948278
TI  - Investigating mitochondria as a target for treating age-related macular
      degeneration.
AB  - Age-related macular degeneration (AMD) is the leading cause of blindness among
      older adults in the developed world. Although the pathological mechanisms have
      not been definitively elucidated, evidence suggests a key role for mitochondrial
      (mt) dysfunction. The current study used our unique collection of human retinal
      samples graded for the donor's stage of AMD to address fundamental questions
      about mtDNA damage in the retina. To evaluate the distribution of mtDNA damage in
      the diseased retina, damage in the retinal pigment epithelium (RPE) and neural
      retina from individual donors were compared. To directly test a long-held belief
      that the macula is selectively damaged with AMD, RPE mtDNA damage was measured in
      the macula and peripheral sections from individual donors. Small segments of the
      entire mt genome were examined to determine whether specific regions are
      preferentially damaged. Our results show that mtDNA damage is limited to the RPE,
      equivalent mtDNA damage is found in the macular and peripheral RPE, and sites of
      damage are localized to regions of the mt genome that may impact mt function.
      These results provide a scientific basis for targeting the RPE mitochondria with
      therapies that protect and enhance mt function as a strategy for combating AMD. 

PMID- 25948279
TI  - Endothelial progenitor cells inhibit platelet function in a P-selectin-dependent
      manner.
AB  - BACKGROUND: The role of endothelial progenitor cells (EPCs) in vascular repair is
      related to their recruitment at the sites of injury and their interaction with
      different components of the circulatory system. We have previously shown that
      EPCs bind and inhibit platelet function and impair thrombus formation via
      prostacyclin secretion, but the role of EPC binding to platelet P-selectin in
      this process has not been fully characterized. In the present study, we assessed
      the impact of EPCs on thrombus formation and we addressed the implication of P
      selectin in this process. METHODS: EPCs were generated from human peripheral
      blood mononuclear cells cultured on fibronectin in conditioned media. The impact
      of EPCs on platelet aggregation and thrombus formation was investigated in P
      selectin deficient (P-sel(-/-)) mice and their wild-type (WT) counterparts.
      RESULTS: EPCs significantly and dose-dependently impaired collagen-induced whole
      blood platelet aggregation in WT mice, whereas no effects were observed in P-sel(
      /-) mice. Moreover, in a ferric chloride-induced arterial thrombosis model,
      infusion of EPCs significantly reduced thrombus formation in WT, but not in P
      sel(-/-) mice. Furthermore, the relative mass of thrombi generated in EPC-treated
      P-sel(-/-) mice were significantly larger than those in EPC-treated WT mice, and
      the number of EPCs recruited within the thrombi and along the arterial wall was
      reduced in P-sel(-/-) mice as compared to WT mice. CONCLUSION: This study shows
      that EPCs impair platelet aggregation and reduce thrombus formation via a
      cellular mechanism involving binding to platelet P-selectin. These findings add
      new insights into the role of EPC-platelet interactions in the regulation of
      thrombotic events during vascular repair.

PMID- 25948280
TI  - CYCLIN-DEPENDENT KINASE G2 regulates salinity stress response and salt mediated
      flowering in Arabidopsis thaliana.
AB  - Cyclin-dependent protein kinases are involved in many crucial cellular processes
      and aspects of plant growth and development, but their precise roles in abiotic
      stress responses are largely unknown. Here, Arabidopsis thaliana CYCLIN-DEPENDENT
      KINASE G2 (CDKG2) was shown to act as a negative regulator of the salinity stress
      response, as well as being involved in the control of flowering time. GUS
      expression experiments based on a pCDKG2::GUS transgene suggested that CDKG2 was
      expressed throughout plant development, with especially high expression levels
      recorded in the seed and in the flower. The loss-of-function of CDKG2 led to an
      increased tolerance of salinity stress and the up-regulation of the known stress
      responsive genes SOS1, SOS2, SOS3, NHX3, RD29B, ABI2, ABI3, MYB15 and P5CS1.
      Flowering was accelerated in the cdkg2 mutants via the repression of FLC and the
      consequent up-regulation of FT, SOC1, AP1 and LFY. Transgenic lines
      constitutively expressing CDKG2 showed greater sensitivity to salinity stress and
      were delayed in flowering. Furthermore, the CDKG2 genotype affected the response
      of flowering time to salinity stress. Our data connect CDKG2 to undescribed
      functions related to salt stress tolerance and flowering time through the
      regulation of specific target genes. 

PMID- 25948281
TI  - Cyanobacteria blooms and non-alcoholic liver disease: evidence from a county
      level ecological study in the United States.
AB  - BACKGROUND: Harmful cyanobacterial blooms present a global threat to human
      health. There is evidence suggesting that cyanobacterial toxins can cause liver
      damage and cancer. However, because there is little epidemiologic research on the
      effects of these toxins in humans, the excess risk of liver disease remains
      uncertain. The purpose of this study is to estimate the spatial distribution of
      cyanobacterial blooms in the United States and to conduct a Bayesian statistical
      analysis to test the hypothesis that contamination from cyanobacterial blooms is
      a potential risk factor for non-alcoholic liver disease. METHODS: An ecological
      study design was employed, in which county-specific gender and age standardized
      mortality rates (SMR) of non-alcoholic liver disease in the United States were
      computed between 1999 and 2010. Bloom coverage maps were produced based on
      estimated phycocyanin levels from MERIS (Medium Resolution Imaging Spectrometer)
      water color imageries from 08/01/2005 to 09/30/2005. A scan statistical tool was
      used to identify significant clusters of death from non-alcoholic liver disease.
      A map of local indicator of spatial association (LISA) clusters and a Bayesian
      spatial regression model were used to analyze the relationship between
      cyanobacterial bloom coverage and death from non-alcoholic liver disease.
      RESULTS: Cyanobacterial blooms were found to be widely spread in the United
      States, including coastal areas; 62% of the counties (1949 out of 3109) showed
      signs of cyanobacterial blooms measured with MERIS. Significant clusters of
      deaths attributable to non-alcoholic liver disease were identified in the coastal
      areas impacted by cyanobacterial blooms. Bayesian regression analysis showed that
      bloom coverage was significantly related to the risk of non-alcoholic liver
      disease death. The risk from non-alcoholic liver disease increased by 0.3% (95%
      CI, 0.1% to 0.5%) with each 1% increase in bloom coverage in the affected county
      after adjusting for age, gender, educational level, and race. CONCLUSIONS: At the
      population level, there is a statistically significant association between
      cyanobacterial blooms and non-alcoholic liver disease in the contiguous United
      States. Remote sensing-based water monitoring provides a useful tool for
      assessing health hazards, but additional studies are needed to establish a
      specific association between cyanobacterial blooms and liver disease.

PMID- 25948282
TI  - New recurrent BRCA1/2 mutations in Polish patients with familial breast/ovarian
      cancer detected by next generation sequencing.
AB  - BACKGROUND: Targeted PCR-based genetic testing for BRCA1 and BRCA2 can be
      performed at a lower cost than full gene testing; however, it may overlook
      mutations responsible for familial breast and/or ovarian cancers. In the present
      study, we report the utility of next generation sequencing (NGS) to identify new
      pathogenic variants of BRCA1/2. METHODS: BRCA1 and BRCA2 exons were amplified
      using the Ion AmpliSeq BRCA1/2 Panel and sequenced on the Ion Torrent PGM
      sequencer in 512 women with familial and/or only early onset breast and/or
      ovarian cancers who were negative for selected BRCA1/2 mutations. RESULTS: 146
      single nucleotide variants (SNVs) and 32 indels were identified. Of them, 14 SNVs
      and 17 indels were considered as pathogenic or likely pathogenic. One and 18
      pathogenic mutations had been detected previously in the Polish and other
      populations, respectively, and 12 deleterious mutations were previously unknown.
      Eight mutations were recurrent; Q563X (BRCA1), N3124I (BRCA2) and c.4516delG
      (BRCA1) were found in eight, six and four patients, respectively, and two other
      mutations (c.9118-2A > G and c.7249delCA in BRCA2) were detected in three
      patients each. Altogether, BRCA1/2 pathogenic mutations were identified in 52 out
      of 512 (10%) patients. CONCLUSIONS: NGS substantially improved the detection
      rates of a wide spectrum of mutations in Polish patients with familial breast
      and/or ovarian cancer. Although targeted screening for specific BRCA1 mutations
      can be offered to all Polish breast or ovarian cancer patients, NGS-based testing
      is justified in patients with breast or ovarian cancer likely related to BRCA1/2
      who test negative for the selected BRCA1/2 pathogenic mutations.

PMID- 25948283
TI  - Short-Term Changes in Body Composition and Response to Micronutrient
      Supplementation After Laparoscopic Sleeve Gastrectomy.
AB  - BACKGROUND: We evaluated dietary intakes, body composition, micronutrient
      deficiency, and response to micronutrient supplementation in 47 patients before
      and for 6 months after laparoscopic sleeve gastrectomy (LSG). METHODS: Before, 3,
      and 6 months after LSG, we measured dietary intakes with food-frequency
      questionnaires, body composition with bioimpedance analysis (BIA) and
      bioelectrical vector analysis (BIVA), and plasma concentrations of iron, Zn,
      water-, and lipo-soluble vitamins. RESULTS: After LSG, energy intake
      significantly decreased and patients lost weight, fat mass, and free-fat mass.
      BIVA showed a substantial loss of soft tissue body cell mass (BCM) with no change
      in hydration. Before surgery, 15 % of patients were iron deficient, 30 % had low
      levels of zinc and/or water-soluble vitamins, and 32 % of vitamin 25(OH)-D3. We
      treated iron deficiency with ferrous sulfate, isolated folate deficiency with N5
      methyiltetrahydrofolate-Ca-pentahydrate, and deficiencies in vitamin B1, B12, or
      Zn, with or without concomitant folate deficiency, with multivitamin. No
      supplementation was given to vitamin 25(OH)-D3 deficient patients. At first
      follow-up, 7 % of patients developed new deficiencies in iron, 7 % in folic acid
      (n = 3), and 36 % in water-soluble vitamins and/or zinc whereas no new deficit in
      vitamin 25(OH)-D3 occurred. At final follow-up, deficiencies were corrected in
      all patients treated with either iron or folate but only in 32 % of those
      receiving multivitamin. Vitamin 25(OH)-D3 deficiency was corrected in 73 % of
      patients even though these patients were not supplemented. CONCLUSION: LSG
      induced weight loss is accompanied by a decrease in BCM with no body fluid
      alterations. Deficiencies in water-soluble vitamins and Zn respond poorly to
      multivitamin supplementation.

PMID- 25948285
TI  - Hospitalisation leads to functional decline in the over 70s, study finds.

PMID- 25948284
TI  - Gastrobronchial Fistula: A Serious Complication of Sleeve Gastrectomy. Results of
      a French Multicentric Study.
AB  - BACKGROUND: Gastrobronchial fistula (GBF) is a complication of esophageal,
      splenic, or antireflux surgeries and was recently described as a complication of
      bariatric surgery. Our aim was to study all cases of GBF after laparoscopic
      sleeve gastrectomy (LSG) managed in five French university bariatric centers in
      order to establish the incidence and to evaluate the different treatments of this
      complication. METHODS: We retrospectively studied 13 patients which developed GBF
      after LSG performed between March 2007 and August 2012. Patients were separated
      into two groups: patients who had early gastric fistula which has evolved into a
      GBF (group 1) and patients who had a late gastric fistula, either directly GBF or
      a late gastric fistula evolved in GBF (group 2). RESULTS: Group 1 consisted of
      five patients and group 2 of eight patients. All patients were undernourished at
      diagnosis. Management of GBF was a combined thoraco-abdominal surgery with
      gastrojejunal anastomosis (n = 5) or total gastrectomy (n = 1), multiple
      endoscopic treatment and thoracic surgery (n = 3), an endobronchial valve (n =
      1), total gastrectomy and thoracic drainage (n = 1), and transorificial
      intubation with thoracic surgery or drainage (n = 2). There was no mortality. All
      GBF healed. CONCLUSIONS: GBF after LSG is a serious complication which is not
      anecdotal. Most of the early gastric fistulas occuring after LSG become chronic
      and can evolve into a GBF. Surgical approach is an effective treatment.
      Endobronchial valve is a novel alternative.

PMID- 25948286
TI  - A qualitative study of transgender individuals' experiences in residential
      addiction treatment settings: stigma and inclusivity.
AB  - BACKGROUND: While considerable research has been undertaken on addiction
      treatment, the experiences of transgender individuals who use drugs are rarely
      explored in such research, as too often transgender individuals are excluded
      entirely or grouped with those of sexual minority groups. Consequently, little is
      known about the treatment experiences in this population. Thus, we sought to
      qualitatively investigate the residential addiction treatment experiences of
      transgender individuals who use illicit drugs in a Canadian setting. METHODS: In
      depth semi-structured interviews were conducted with 34 transgender individuals
      in Vancouver, Canada between June 2012 and May 2013. Participants were recruited
      from three open prospective cohorts of individuals who use drugs and an open
      prospective cohort of sex workers. Theory-driven and data-driven approaches were
      used to analyze the data and two transgender researcher assistants aided with the
      coding and the interpretation of data in a process called participatory analysis.
      RESULTS: Fourteen participants had previous experience of addiction treatment and
      their experiences varied according to whether their gender identity was accepted
      in the treatment programs. Three themes emerged from the data that characterized
      individuals' experiences in treatment settings: (1) enacted stigma in the forms
      of social rejection and violence, (2) transphobia and felt stigma, and (3) "trans
      friendly" and inclusive treatment. Participants who reported felt and enacted
      stigma, including violence, left treatment prematurely after isolation and
      conflicts. In contrast, participants who felt included and respected in treatment
      settings reported positive treatment experiences. CONCLUSIONS: The study findings
      demonstrate the importance of fostering respect and inclusivity of gender diverse
      individuals in residential treatment settings. These findings illustrate the need
      for gender-based, anti-stigma policies and programs to be established within
      existing addiction treatment programs. Additionally, it is vital to establish
      transgender and/or LGBTQ specific treatment programs as recommended by the
      participants in this study.

PMID- 25948288
TI  - Quetiapine-associated leucopenia and thrombocytopenia: a case report.
AB  - BACKGROUND: There have been few reports regarding quetiapine-associated
      hematological effects other than white-blood-cell alteration. We present the
      first reported Han-Chinese case that developed leucopenia and thrombocytopenia
      after taking quetiapine. CASE PRESENTATION: We present a case of a person with a
      bipolar I disorder who experienced leucopenia and thrombocytopenia after taking
      400 mg/day of quetiapine and 1000 mg/day of valproic acid for three and one-half
      months. The hematological toxicity abated upon the discontinuation of both drugs.
      However, due to the intolerable side effects of the replaced antipsychotic
      (haloperidol), and according to the patient's preference, we prescribed
      quetiapine and valproic acid again. There was a recurrence of leucopenia and a
      decreased platelet count by the sixth day. The adverse effects disappeared soon
      after we discontinued quetiapine, while keeping valproic acid treatment.
      CONCLUSION: Quetiapine-associated leucopenia and thrombocytopenia seems
      reversible but possibly fatal. Therefore, clinical practitioners should be aware
      of this adverse reaction.

PMID- 25948289
TI  - Resident and Facility Factors Associated With the Incidence of Urinary Tract
      Infections Identified in the Nursing Home Minimum Data Set.
AB  - OBJECTIVE: This research examined resident and facility-specific factors
      associated with a diagnosis of a urinary tract infection (UTI) in the nursing
      home setting. METHOD: Minimum Data Set and Online Survey, Certification and
      Reporting system data were used to identify all nursing home residents in the
      United States on April 1, 2006, who did not have a UTI ( n = 1,138,418).
      Residents were followed until they contracted a UTI (9.5%), died (8.3%), left the
      nursing home (33.2%), or the year ended (49.0%). A Cox proportional hazards model
      was estimated, controlling for resident and facility characteristics and for the
      state of residence. RESULT: The presence of an indwelling catheter was the
      primary predictor of whether a resident contracted a UTI (adjusted incidence
      ratio = 3.35, p < .001), but only 6.1% of the residents in the sample had such a
      catheter. Therefore, only one eighth of the UTIs were contracted by residents
      with a catheter. Thus, subsequent analysis examined the populations with and
      without catheters separately. Demographic characteristics (such as age) have a
      much greater association with incidence among residents without catheters. The
      association with facility factors such as percentage of Medicaid residents, for
      profit, and chain status was less significant. Estimates regarding staffing
      levels indicate that increased contact hours with more highly educated nursing
      staff are associated with less catheter use. DISCUSSION: Several facility
      specific risk factors are of significance. Of significance, UTIs may be reduced
      by modifying factors such as staffing levels.

PMID- 25948287
TI  - Efficacy of low-intensity psychological intervention applied by ICTs for the
      treatment of depression in primary care: a controlled trial.
AB  - BACKGROUND: Depression is one of the most common disorders in Psychiatric and
      Primary Care settings and is associated with significant disability and economic
      costs. Low-intensity psychological interventions applied by Information and
      Communication Technologies (ICTs) could be an efficacious and cost-effective
      therapeutic option for the treatment of depression. The aim of this study is to
      assess 3 low-intensity psychological interventions applied by ICTs (healthy
      lifestyle, positive affect and mindfulness) in Primary Care; significant efficacy
      for depression treatment has previously showed in specialized clinical settings
      by those interventions, but ICTs were not used. METHOD: Multicenter controlled
      randomized clinical trial in 4 parallel groups. Interventions have been designed
      and on-line device adaptation has been carried out. Subsequently, the randomized
      controlled clinical trial will be conducted. A sample of N = 240 mild and
      moderate depressed patients will be recruited and assessed in Primary Care
      settings. Patients will be randomly assigned to a) healthy lifestyle
      psychoeducational program + improved primary care usual treatment (ITAU), b)
      focused program on positive affect promotion + ITAU c) mindfulness + ITAU or d)
      ITAU. The intervention format will be one face to face session and four ICTs on
      line modules. Patients will be diagnosed with MINI psychiatric interview. Main
      outcome will be PHQ-9 score. They will be also assessed by SF-12 Health Survey,
      Client Service Receipt Inventory, EuroQoL-5D questionnaire, Positive and Negative
      Affect Scale, Five Facet Mindfulness Questionnaire and the Pemberton Happiness
      Index. Patients will be assessed at baseline, post, 6 and 12 post-treatment
      months. An intention to treat and per protocol analysis will be performed.
      DISCUSSION: Low-intensity psychological interventions applied by Information and
      Communication Technologies have been not used before in Spain and could be an
      efficacious and cost-effective therapeutic option for depression treatment. The
      strength of the study is that it is the first multicenter controlled randomized
      clinical trial of three low intensity and self-guided interventions applied by
      ICTs (healthy lifestyle psychoeducational program; focused program on positive
      affect promotion and brief intervention based on mindfulness) in Primary Care
      settings. TRIAL REGISTRATION: Current Controlled Trials ISRCTN82388279 .
      Registered 16 April 2014.

PMID- 25948290
TI  - Isokinetic Dynamometry in Healthy Versus Sarcopenic and Malnourished Elderly:
      Beyond Simple Measurements of Muscle Strength.
AB  - This study quantified systematic and intraindividual variability among three
      repetitions of concentric isokinetic knee extension and flexion tests to
      determine velocity-related differences in peak torque (PT) and mean power (MP) in
      healthy elderly (HE) versus sarcopenic and malnourished elderly (SME). In total,
      107 HE ( n = 54 men, n = 53 women) and 261 SME ( n = 101 men, n = 160 women)
      performed three maximal concentric isokinetic knee extension and flexion
      repetitions at 60 degrees .s-1 and 180 degrees .s-1. PT for Repetition 3 was
      lower than Repetitions 1 and 2, while MP for Repetition 1 was lower than
      Repetitions 2 and 3 in SME. Intraindividual variability among repetitions was
      correlated with strength, but not age, and was greater in SME, during knee
      flexion, and at 180 degrees .s-1. Velocity-related decreases in PT from 60
      degrees .s-1 to 180 degrees .s-1 were more pronounced in SME. In summary, (a) the
      repetition with the highest PT value may be the best indicator of maximal
      strength, while the average may indicate strength maintenance in SME; (b)
      intraindividual variability among repetitions reflects functional decrements from
      HE to SME; and

PMID- 25948291
TI  - Commentary on "Is the system really the solution? Operating costs in hospital
      systems": limits to system efficiency in centralized hospital systems:
      illustration from the University of Pennsylvania Health System.

PMID- 25948293
TI  - Comparison of performance of the test of memory malingering and word memory test
      in a criminal forensic sample.
AB  - Compared with the amount of neuropsychological literature surrounding response
      bias in civil litigation, there is little regarding criminal cases. This study
      adds to the criminal forensic neuropsychological literature by comparing the Test
      of Memory Malingering (TOMM) and the Word Memory Test (WMT) in a criminal
      forensic setting utilizing a criterion-groups design. Subjects were classified
      into two groups based on their performance on at least two other freestanding
      performance validity tests. The WMT demonstrated good sensitivity (95.1%) but
      poor specificity (68.4%) when Genuine Memory Impaired Profiles (GMIPs) were not
      considered. Inclusion of GMIPs reduced the sensitivity to 56.1% but increased the
      specificity to 94.7%. The TOMM evidenced better sensitivity but poorer
      specificity than the WMT with GMIPs. Conjoint use of the tests was also
      considered. Receiver operating characteristics and other classification
      statistics for each measure are presented. Results support the use of these
      measures in a criminal forensic population. 

PMID- 25948296
TI  - [Regulatory science on biomarker usage for development and proper use of drugs].

PMID- 25948294
TI  - A Monoclonal Antibody to ADAM17 Inhibits Tumor Growth by Inhibiting EGFR and Non
      EGFR-Mediated Pathways.
AB  - ADAM17 is the primary sheddase for HER pathway ligands. We report the discovery
      of a potent and specific ADAM17 inhibitory antibody, MEDI3622, which induces
      tumor regression or stasis in many EGFR-dependent tumor models. The inhibitory
      activity of MEDI3622 correlated with EGFR activity both in a series of tumor
      models across several indications as well in as a focused set of head and neck
      patient-derived xenograft models. The antitumor activity of MEDI3622 was superior
      to that of EGFR/HER pathway inhibitors in the OE21 esophageal model and the
      COLO205 colorectal model suggesting additional activity outside of the EGFR
      pathway. Combination of MEDI3622 and cetuximab in the OE21 model was additive and
      eradicated tumors. Proteomics analysis revealed novel ADAM17 substrates that
      function outside of the HER pathways and may contribute toward the antitumor
      activity of the monoclonal antibody.

PMID- 25948295
TI  - BRAF Inhibition Decreases Cellular Glucose Uptake in Melanoma in Association with
      Reduction in Cell Volume.
AB  - BRAF kinase inhibitors have dramatically affected treatment of BRAF(V600E) (/)
      (K)-driven metastatic melanoma. Early responses assessed using
      [(18)F]fluorodeoxyglucose uptake-positron emission tomography (FDG-PET) have
      shown dramatic reduction of radiotracer signal within 2 weeks of treatment.
      Despite high response rates, relapse occurs in nearly all cases, frequently at
      sites of treated metastatic disease. It remains unclear whether initial loss of
      (18)FDG uptake is due to tumor cell death or other reasons. Here, we provide
      evidence of melanoma cell volume reduction in a patient cohort treated with BRAF
      inhibitors. We present data demonstrating that BRAF inhibition reduces melanoma
      glucose uptake per cell, but that this change is no longer significant following
      normalization for cell volume changes. We also demonstrate that volume
      normalization greatly reduces differences in transmembrane glucose transport and
      hexokinase-mediated phosphorylation. Mechanistic studies suggest that this loss
      of cell volume is due in large part to decreases in new protein translation as a
      consequence of vemurafenib treatment. Ultimately, our findings suggest that cell
      volume regulation constitutes an important physiologic parameter that may
      significantly contribute to radiographic changes observed in clinic.

PMID- 25948297
TI  - [Regulatory science for the proper evaluation of biomarkers (overview)].
AB  - New drug development (NDD) for intractable diseases such as cancer and
      Alzheimer's disease has been challenging in recent years because it is difficult
      to evaluate the therapeutic efficacy of new drugs and the response of individual
      patients. Thus biomarkers might be a useful tool to facilitate NDD because they
      can be used to evaluate accurately drug responses. Biomarkers include proteins,
      metabolites, and genetic targets; imaging data and can also be used in pre
      clinical studies, clinical trials, and post-marketing surveillance. In pre
      clinical studies, biomarkers are used as an index of the pharmacological and
      toxicological effects of a new drug, which may help to predict the clinical
      response. In clinical studies, biomarkers are widely used as an index of clinical
      efficacy and safety for dose-adjustment and for patient selection. In post
      clinical studies, biomarkers may facilitate the evaluation of drug responses, as
      well as aid improvements in drug efficacy. Several points should be considered
      for biomarker-guided NDD. First, the clinical study design is very important and
      must be suitable to permit the use of the relevant biomarkers. The analytical
      methods should be carefully evaluated, and evidence should be provided regarding
      the physiological significance and relevance of the biomarker with regard to its
      intended use. Regulatory sciences are required to resolve these issues and bridge
      the gap between basic science and clinical studies that involve biomarkers.

PMID- 25948298
TI  - [Investigation of Predisposition Biomarkers to Identify Risk Factors for Drug
      induced Liver Injury in Humans: Analyses of Endogenous Metabolites in an Animal
      Model Mimicking Human Responders to APAP-induced Hepatotoxicity].
AB  - Drug-induced liver injury is a main reason of regulatory action pertaining to
      drugs, including restrictions to clinical indications and withdrawal from the
      marketplace. Acetaminophen (APAP) is a commonly used and effective
      analgesic/antipyretic agent and relatively safe drug even in long-term treatment.
      However, it is known that APAP at therapeutic doses may cause hepatotoxicity in
      some individuals. Hence great efforts have been made to identify risk factors for
      APAP-induced chronic hepatotoxicity. We investigated the contribution of
      undernourishment to susceptibility to APAP-induced chronic hepatotoxicity using
      an animal model. We employed daytime restricted fed (RF) rats as a modified
      nutritional state model for human APAP-induced hepatotoxicity. RF and ad libitum
      fed (ALF) rats were given APAP at 0, 300, and 500 mg/kg for 3 months. Plasma and
      urinary glutathione-related metabolomes and liver function parameters were
      measured during the dosing period. Endogenous metabolites forming at different
      levels between the RF and ALF rats could be potential predisposition biomarkers
      for APAP-induced hepatotoxicity. In addition, RF rats were considered a useful
      model to estimate the contribution of nutritional state of patients to APAP
      induced chronic hepatotoxicity. In this article we report our current research
      focusing on nutritional state as risk factor for APAP-induced chronic
      hepatotoxicity and our findings of hepatotoxicity biomarkers.

PMID- 25948299
TI  - [Development of mogamulizumab and establishment of an optimal therapy based on
      genomic biomarkers: from the academic viewpoint].
AB  - Mogamulizumab (Moga; KW-0761) is a defucosylated humanized anti-CC chemokine
      receptor 4 (CCR4) antibody engineered to exert potent antibody-dependent cellular
      cytotoxicity (ADCC). A collaborative investigation with industry in preclinical
      studies has demonstrated in vitro and in vivo efficacy via ADCC for adult T-cell
      leukemia/lymphoma (ATLL) and CCR4-positive peripheral T-cell lymphoma (PTCL). In
      a phase I study, once-weekly administration of mogamulizumab (0.01-1.0 mg/kg) for
      4 weeks was well tolerated. In a phase II study of once-weekly mogamulizumab (1.0
      mg/kg) for 8 weeks in relapsed/refractory ATLL patients, an overall response rate
      of 50% including 30% complete response rate with a median progression-free
      survival of 5.2 months was observed. The drug was subsequently approved by
      Pharmaceuticals and Medical Devices Agency(PMDA) in March 2012. Because CCR4 is
      abundantly expressed on the surface of effector regulatory T cells, a phase I
      study is being conducted to enhance antitumor immune response in patients with
      solid tumors. However, approximately 60% of patients receiving mogamulizumab
      experience skin eruption with 19% showing grade >= 3 rash. Postmarketing
      surveillance of mogamulizumab revealed a 3-4% incidence rate of skin-related
      serious adverse events (SAEs) such as Stevens-Johnson syndrome (SJS) and toxic
      epidermal necrolysis (TEN). Therefore we initiated a search for predictive
      genomic biomarkers in the blood of patients with ATLL or solid tumors prior to
      treatment with mogamulizumab for not only efficacy but also immune-related SAEs.
      We believe the results of this study may lead to safer and more efficient use of
      this agent in the near future.

PMID- 25948300
TI  - [Utilization of Genomic Biomarkers for Post-marketing Safety of Drugs].
AB  - To prevent adverse drug reactions in the post-marketing phase, therapeutic drug
      monitoring and various laboratory tests have been used for decades. Recently,
      data on associations between drug adverse reactions and biomarkers based on
      "omics" technologies/studies have been increasing. Using genomic biomarkers,
      patients at high risk for developing side effects can be distinguished before
      initiating medical treatment, allowing the choice of an appropriate drug/initial
      dosage regimen. Biomarkers based on proteomics or metabolomics can detect the
      onset of adverse reactions at an earlier stage than can be accomplished with
      classical laboratory tests. However, the clinical use of drug safety-related
      biomarkers is still limited compared with biomarkers that predict drug efficacy
      of, for example, molecular-targeted drugs. In this symposium, genomic biomarkers
      associated with the safety of anticancer drugs and idiosyncratic adverse
      reactions are introduced and compared between Japan and other countries.
      Prospective studies evaluating the application of screening tests to prevent
      adverse drug reactions are also shown, and steps necessary to accelerate the use
      of drug safety-related biomarkers are discussed.

PMID- 25948301
TI  - [Current PMDA Activities for Use of Biomarkers in Drug Evaluation].
AB  - Biomarkers (BM) are gradually being recognized as useful tools to evaluate drugs
      from development through post-approval periods. In the past decade, practical use
      of BM has advanced particularly in the field of anti-cancer drug development.
      Regardless of the use of BM, approximately 10% of key clinical trials for new
      drug applications of anti-cancer drugs were conducted as multiregional clinical
      trials. In the era of globalization of drug development, common understanding
      regarding the usefulness and limitations of BM availabilities in drug evaluation
      will contribute to provide better evidence in multiple clinical trials. However,
      only two guidelines regarding BM, i.e., terminologies of pharmacogenomics (E15
      guideline) and document format in BM qualification submission to regulatory
      agencies (E16 guideline), have been harmonized in the International Conference on
      Harmonization of Technical Requirements for Registration of Pharmaceuticals for
      Human Use (ICH) so far. It is important to strengthen international harmonization
      and collaboration among academia, industry, and regulatory agencies, followed by
      the establishment of an international guideline on the application of BM in drug
      evaluation. This article outlines the regulatory perspective on remaining
      challenges and current Pharmaceuticals and Medical Devices Agency (PMDA)
      activities for use of BM in drug evaluation.

PMID- 25948302
TI  - [Frontiers in research of drug transporters aimed at appropriate pain relief by
      narcotic analgesics. Foreword].

PMID- 25948303
TI  - [Role of Scaffold Proteins in Functional Alteration of Small Intestinal P
      glycoprotein by Anti-cancer Drugs].
AB  - Since there is accumulating evidence to indicate that introduction of early
      palliative care for cancer patients may improved their quality of life or
      survival rates, the number of patients receiving pain relief by narcotic
      analgesics in conjunction with chemotherapy is predicted to increase. Therefore
      to provide effective combination treatments it is important to evaluate basic
      evidence regarding drug-drug interactions between anti-cancer drugs and
      narcotics. We have focused on P-glycoprotein (P-gp), a drug efflux transporter,
      in small intestine where the absorption process of drugs administered via oral
      route is greatly limited. Then, we revealed that repeated oral treatment with
      etoposide (ETP) increases P-gp levels in the small intestinal membrane via
      RhoA/ROCK activation, leading to decrease in analgesia of morphine, a P-gp
      substrate drug, with alteration of its disposition after oral administration.
      Furthermore, we found that activation of ezrin/radixin/moesin (ERM), scaffold
      proteins that regulate plasma membrane localization or function of certain plasma
      membrane proteins such as P-gp, are involved in this mechanism. Of particular
      interest is that among ERM proteins, radixin may contribute, at least in part, to
      increased expression of P-gp in the small intestine under repeated oral treatment
      with ETP.

PMID- 25948304
TI  - [The blood-brain barrier transport mechanism controlling analgesic effects of
      opioid drugs in CNS].
AB  - The transport of opioid analgesics across the blood-brain barrier (BBB) is an
      important determinant of their therapeutic effects. The human brain is protected
      by the BBB, which consists of brain capillary endothelial cells linked with tight
      junctions. It is well established that the polarized expression of numerous
      transporters and receptors at the brain capillary endothelial cells controls the
      blood-brain exchange of nutrients, waste products deriving from neurotransmitter
      substances, and drugs. Morphine is a substrate of P-glycoprotein and the P
      glycoprotein-mediated efflux transport at the BBB maintains a lower unbound
      concentration of morphine in the brain compared with plasma. On the other hand,
      oxycodone has 3 times higher unbound concentration in the brain than plasma,
      suggesting an active transport mechanism of oxycodone across the BBB into the
      brain. In vitro transport study using BBB model cells showed that oxycodone is
      efficiently transported by a proton-coupled organic cation antiporter. Human BBB
      model cells also retain the proton-coupled organic cation antiporter. Although
      adjuvant analgesics include many cationic drugs that interact with oxycodone
      transport across the BBB at relatively high concentrations, these drugs would
      enhance the antinociceptive effects of oxycodone with little effect on oxycodone
      pharmacokinetics, including brain distribution at therapeutically or
      pharmacologically relevant concentrations. These findings support the idea that
      proton-coupled organic cation antiporter-mediated transport of oxycodone at the
      BBB plays a role in determining the therapeutic efficacy of this opioid analgesic
      drug.

PMID- 25948305
TI  - [Altered expression of transporter and analgesic of morphine in neuropathic pain
      mice].
AB  - It is known that morphine is less effective for patients with neuropathic pain,
      accounting for approximately 70% of cancer patients with severe pain. One of the
      causes of the decline is reported as a decreased function of the MU-opioid
      receptor, which binds to the active metabolites of morphine in the mesencephalic
      ventral tegmental area. However, the details of this mechanism are not
      understood. We hypothesized that a decrease in the concentration of morphine in
      the brain reduces its analgesic effect on neuropathic pain, and found that the
      analgesic effect of morphine was correlated with its concentration in the brain.
      We examined the reason for the decreased concentration of morphine in the brain
      in case of neuropathic pain. We discovered increased P-glycoprotein (P-gp)
      expression in the small intestine, increased expression and activity of UGT2B in
      the liver, and increased P-gp expression in the brain under conditions of
      neuropathic pain. In this symposium, we argue that low brain morphine
      concentration is considered one of the causes of lower sensitivity to morphine in
      neuropathic pain patients.

PMID- 25948306
TI  - [Interindividual variation of pharmacokinetic disposition of and clinical
      responses to opioid analgesics in cancer pain patients].
AB  - Use of prescription opioids for cancer pain according to the World Health
      Organization analgesic ladder has been accepted in Japan. Although oxycodone and
      fentanyl are commonly used as first-line analgesics, a few clinical reports have
      been published on interindividual variations in their pharmacokinetics and
      clinical responses in cancer patients. (1) Some factors relating to CYP2D6,
      CYP3A, ATP-binding cassette sub-family B member 1 (ABCB1), and opioid receptor mu
      1 (OPRM1) involve oxycodone pharmacokinetics and sensitivity in humans. The
      relations between their genetic variations and clinical responses to oxycodone
      are being revealed in limited groups. In our study, the impact of genetic
      variants and pharmacokinetics on clinical responses to oxycodone were evaluated
      in Japanese populations. (2) Opioid switching improves the opioid tolerance
      related to the balance between analgesia and adverse effects. Some patients have
      difficulty in obtaining better opioid tolerance in recommended conversion ratios.
      The activities of CYP3A, ABCB1, and OPRM1 contribute to the interindividual
      variations in clinical responses to fentanyl in cancer patients. However, the
      variations in opioid switching remain to be clarified in clinical settings. In
      our study, genetic factors related to interindividual variations in clinical
      responses in opioid switching to fentanyl were revealed in Japanese populations.
      In this symposium review, the possibility of approaches to personalized
      palliative care using opioids based on genetic variants of CYP2D6, CYP3A5, ABCB1,
      and OPRM1 is discussed.

PMID- 25948307
TI  - [Imaging in vivo redox metabolism. Foreword].

PMID- 25948308
TI  - [Radiation therapy and redox imaging].
AB  - Radiation therapy kills cancer cells in part by flood of free radicals. Radiation
      ionizes and/or excites water molecules to create highly reactive species, i.e.
      free radicals and/or reactive oxygen species. Free radical chain reactions
      oxidize biologically important molecules and thereby disrupt their function.
      Tissue oxygen and/or redox status, which can influence the course of the free
      radical chain reaction, can affect the efficacy of radiation therapy. Prior
      observation of tissue oxygen and/or redox status is helpful for planning a safe
      and efficient course of radiation therapy. Magnetic resonance-based redox imaging
      techniques, which can estimate tissue redox status non-invasively, have been
      developed not only for diagnostic information but also for estimating the
      efficacy of treatment. Redox imaging is now spotlighted to achieve radiation
      theranostics.

PMID- 25948309
TI  - [Redox Molecular Imaging Using ReMI].
AB  - Tissue redox status is one of the most important parameters to maintain
      homeostasis in the living body. Numerous redox reactions are involved in
      metabolic processes, such as energy production in the mitochondrial electron
      transfer system. A variety of intracellular molecules such as reactive oxygen
      species, glutathione, thioredoxins, NADPH, flavins, and ascorbic acid may
      contribute to the overall redox status in tissues. Breakdown of redox balance may
      lead to oxidative stress and can induce many pathological conditions such as
      cancer, neurological disorders, and aging. Therefore imaging of tissue redox
      status and monitoring antioxidant levels in living organisms can be useful in the
      diagnosis of disease states and assessment of treatment response. In vivo redox
      molecular imaging technology such as electron spin resonance imaging (ESRI),
      magnetic resonance imaging (MRI), and dynamic nuclear polarization (DNP)-MRI
      (redox molecular imaging; ReMI) is emerging as a viable redox status imaging
      modality. This review focuses on the application of magnetic resonance
      technologies using MRI or DNP-MRI and redox-sensitive contrast agents.

PMID- 25948310
TI  - [Development of a new redox molecular imaging method].
AB  - For indirect tissue observation, electron-spin, Overhauser-enhanced, dynamic
      nuclear polarization magnetic resonance imaging (DNP-MRI) is a useful technique.
      However, its sensitivity and resolution are low compared with the clinical MRI
      apparatus. By switching to electron spin resonance (ESR) excitation, the magnetic
      field of the NMR detection, field cycle technique, which aims to improve
      resolution, was proposed. However, the effect of eddy currents or current value
      was altered unsatisfactorily. A team at Kyushu University proposed a new DNP-MRI
      technique capable of improving NMR detection field by preparing in advance a
      magnetic field, which was connected by the sample transport system. By developing
      a mobile MRI method that can be used while moving, and fastening the sample in a
      disk that rotates at a constant speed, they have developed a circular transport
      DNP-MRI method that greatly reduces the load on the sample. The circular
      transport DNP-MRI system comprises a circular sample transport system, detection
      of an MRI magnetic field of 1.5 T, and ESR excitation magnetic field of 20 mT.
      The developed DNP-MRI had a clear glass tube phantom and resolution of 0.15 mm,
      and was successful in imaging multiple radical resonant points. It has been
      commercialized by Japan Redox Limited. In the process of equipment
      commercialization, a new digital spectrometer has been developed, which expanded
      the MRI apparatus.

PMID- 25948312
TI  - [Influence of systemic inflammatory response syndrome on the pharmacokinetics of
      vancomycin].
AB  - Therapeutic drug monitoring (TDM) of vancomycin (VCM) is recommended to minimize
      its nephrotoxicity and maximize efficacy. Recently, the concept of systemic
      inflammatory response syndrome (SIRS) has been introduced to describe a clinical
      state resulting from the actions of complex intrinsic mediators in an acute-phase
      systemic response. However, there are few reports on the pharmacokinetics of VCM
      in patients with SIRS. This study investigated the effect of SIRS on the
      pharmacokinetics of VCM by analyzing the predictability of TDM and
      pharmacokinetic parameters in 31 non-SIRS patients and 52 SIRS patients, with
      stratification by SIRS score. The mean prediction error (ME) and mean absolute
      prediction error in SIRS score 2 and 3 patients differed from those in non-SIRS
      patients. The ME in the score 4 group showed a negative value. In the comparison
      of pharmacokinetic parameters by SIRS score, a significantly lower CL(vcm) value
      was observed at score 4 compared with scores 2 and 3, a higher Vd value was
      observed at score 4 compared with non-SIRS and at score 3, and a longer T1/2 was
      observed at score 2. In the comparison of patient characteristics by SIRS score,
      albumin, aspartate aminotransferase, and alanine aminotransferase levels showed
      differences among the scores. However, no correlation was observed between VCM
      pharmacokinetics and these three laboratory parameters. These findings suggest
      that the pharmacokinetics of VCM may be affected by the pathology of SIRS rather
      than by patient characteristics.

PMID- 25948311
TI  - [Redox and microglia in the pathophysiology of schizophrenia].
AB  - Altered antioxidant status has been implicated in schizophrenia. Microglia are
      major sources of free radicals such as superoxide in the brain, and play crucial
      roles in various brain diseases. Recent postmortem and imaging studies have
      indicated microglial activation in the brain of schizophrenia patients. Animal
      models that express some phenotypes of schizophrenia have revealed the underlying
      microglial pathology. In addition, minocycline, an antibiotic and the best known
      inhibitor of microglial activation, has therapeutic efficacy in schizophrenia. We
      have recently revealed that various antipsychotics directly affect microglia via
      proinflammatory reactions such as oxidative stress, by in vitro studies using
      rodent microglial cells. Based on these findings, we have suggested that
      microglia are crucial players in the brain in schizophrenia, and modulating
      microglia may be a novel therapeutic target. In this review paper, we introduce
      our hypothesis based on the above evidence. The technique of in vivo molecular
      redox imaging is expected to be a powerful tool to clarify this hypothesis.

PMID- 25948313
TI  - [Studies Using Text Mining on the Differences in Learning Effects between the KJ
      and World Cafe Method as Learning Strategies].
AB  - The KJ method (named for developer Jiro Kawakita; also known as affinity
      diagramming) is widely used in participatory learning as a means to collect and
      organize information. In addition, the World Cafe (WC) has recently become
      popular. However, differences in the information obtained using each method have
      not been studied comprehensively. To determine the appropriate information
      selection criteria, we analyzed differences in the information generated by the
      WC and KJ methods. Two groups engaged in sessions to collect and organize
      information using either the WC or KJ method and small group discussions were
      held to create "proposals to improve first-year education". Both groups answered
      two pre- and post- session questionnaires that asked for free descriptions. Key
      words were extracted from the results of the two questionnaires and categorized
      using text mining. In the responses to questionnaire 1, which was directly
      related to the session theme, a significant increase in the number of key words
      was observed in the WC group (p=0.0050, Fisher's exact test). However, there was
      no significant increase in the number of key words in the responses to
      questionnaire 2, which was not directly related to the session theme (p=0.8347,
      Fisher's exact test). In the KJ method, participants extracted the most notable
      issues and progressed to a detailed discussion, whereas in the WC method, various
      information and problems were spread among the participants. The choice between
      the WC and KJ method should be made to reflect the educational objective and
      desired direction of discussion.

PMID- 25948314
TI  - Surface plasmon enhanced spectroscopies and time and space resolved methods:
      general discussion.

PMID- 25948315
TI  - Sanctorius Sanctorius - Chronophysiology in the seventeenth century.

PMID- 25948316
TI  - Synergistic effect of HA and BMP-2 mimicking peptide on the bioactivity of
      HA/PMMA bone cement.
AB  - HA and bone morphogenetic protein-2 (BMP-2) possess superior osteoinductive and
      osteoconductive activities in the repair of bone defects. In this study, a BMP-2
      mimicking oligopeptide (serine-serine-valine-proline-threonine, SSVPT) was
      introduced to the surface of nano-sized HA as the reinforcement phase of a
      poly(methyl methacrylate) (PMMA) cement, and the synergistic action of HA and
      oligopeptide on the bioactivity of HA/PMMA bone cement was investigated.
      Incorporated with 3-trimethoxysilyl propyl methacrylate (MPS)-modified HA, the
      compressive strength, flexural strength, and flexural modulus of HA/PMMA complied
      with the international standardization organization 5833 standard. Adherence
      measurement demonstrated that the introduction of HA and SSVPT could promote the
      adhesion and proliferation of human fetal osteoblast (hFOB) on the surface of
      HA/PMMA cement. The increased alkaline phosphatase (ALP) activity indicated that
      HA/PMMA could promote osteogenic differentiation of hFOB. All of the results
      illuminated that the HA/PMMA cement could be used as a bioactive material for
      regeneration and reconstruction of load-bearing bone. 

PMID- 25948318
TI  - Neonatal surgical care: a review of the burden, progress and challenges in sub
      Saharan Africa.
AB  - The outcome of neonatal surgery has significantly improved over the decades in
      high-income countries. In sub-Saharan Africa (SSA), however, it has lagged
      behind. This is a review of the current state of neonatal surgery in SSA. The
      conditions requiring surgery in the newborn are largely congenital but the rate
      of emergency surgery is high, reaching 40% of all neonatal surgery in some
      settings. Most operations are for intestinal obstruction, commonly owing to
      anorectal malformations and intestinal atresia, as well as abdominal wall
      defects. Many of the patients are delivered outside a hospital facility and often
      present or are referred late and are very ill at time of presentation. The
      morbidity following surgery is high, particularly from surgical site infections
      and respiratory problems. Mortality is high, sometimes reaching 45%, but has
      decreased in recent times. Because of a lack of trained paediatric anaesthetists,
      anaesthesia is often problematic and surgery is sometimes undertaken using a
      local anaesthetic. Further care, including bowel management and orthopaedic and
      neurological rehabilitation, are sub-optimal owing to a lack of appropriately
      trained personnel and financial constraints. While the number of paediatric
      surgeons has increased, there are still few anaesthetists. In order to
      significantly improve the outcome for neonates with surgical problems in SSA,
      paediatric surgery, anaesthesia, neonatology and neonatal nursing capacity need
      to be scaled up and fast-tracked. To make neonatal surgery safer in these
      settings, neonatal intensive care facilities need to be provided and improved. 

PMID- 25948317
TI  - A flow cytometric approach to quantify biofilms.
AB  - Since biofilms are important in many clinical, industrial, and environmental
      settings, reliable methods to quantify these sessile microbial populations are
      crucial. Most of the currently available techniques do not allow the enumeration
      of the viable cell fraction within the biofilm and are often time consuming. This
      paper proposes flow cytometry (FCM) using the single-stain viability dye TO
      PRO((r))-3 iodide as a fast and precise alternative. Mature biofilms of Candida
      albicans and Escherichia coli were used to optimize biofilm removal and
      dissociation, as a single-cell suspension is needed for accurate FCM enumeration.
      To assess the feasibility of FCM quantification of biofilms, E. coli and C.
      albicans biofilms were analyzed using FCM and crystal violet staining at
      different time points. A combination of scraping and rinsing proved to be the
      most efficient technique for biofilm removal. Sonicating for 10 min eliminated
      the remaining aggregates, resulting in a single-cell suspension. Repeated FCM
      measurements of biofilm samples revealed a good intraday precision of
      approximately 5 %. FCM quantification and the crystal violet assay yielded
      similar biofilm growth curves for both microorganisms, confirming the
      applicability of our technique. These results show that FCM using TO-PRO((r))-3
      iodide as a single-stain viability dye is a valid fast alternative for the
      quantification of viable cells in a biofilm.

PMID- 25948319
TI  - Surface- and tip-enhanced Raman spectroscopy reveals spin-waves in iron oxide
      nanoparticles.
AB  - Nanomaterials have the remarkable characteristic of displaying physical
      properties different from their bulk counterparts. An additional degree of
      complexity and functionality arises when oxide nanoparticles interact with
      metallic nanostructures. In this context the Raman spectra due to plasmonic
      enhancement of iron oxide nanocrystals are here reported showing the activation
      of spin-waves. Iron oxide nanoparticles on gold and silver tips are found to
      display a band around 1584 cm(-1) attributed to a spin-wave magnon mode. This
      magnon mode is not observed for nanoparticles deposited on silicon (111) or on
      glass substrates. Metal-nanoparticle interaction and the strongly localized
      electromagnetic field contribute to the appearance of this mode. The localized
      excitation that generates this mode is confirmed by tip-enhanced Raman
      spectroscopy (TERS). The appearance of the spin-waves only when the TERS tip is
      in close proximity to a nanocrystal edge suggests that the coupling of a
      localized plasmon with spin-waves arises due to broken symmetry at the
      nanoparticle border and the additional electric field confinement. Beyond phonon
      confinement effects previously reported in similar systems, this work offers
      significant insights on the plasmon-assisted generation and detection of spin
      waves optically induced. 

PMID- 25948320
TI  - GDF-15 prevents ventilator-induced lung injury by inhibiting the formation of
      platelet-neutrophil aggregates.

PMID- 25948321
TI  - Adaptation, Commissioning, and Evaluation of a 3D Treatment Planning System for
      High-Resolution Small-Animal Irradiation.
AB  - Although spatially precise systems are now available for small-animal
      irradiations, there are currently limited software tools available for treatment
      planning for such irradiations. We report on the adaptation, commissioning, and
      evaluation of a 3-dimensional treatment planning system for use with a small
      animal irradiation system. The 225-kV X-ray beam of the X-RAD 225Cx
      microirradiator (Precision X-Ray) was commissioned using both ion-chamber and
      radiochromic film for 10 different collimators ranging in field size from 1 mm in
      diameter to 40 * 40 mm(2) A clinical 3-dimensional treatment planning system
      (Metropolis) developed at our institution was adapted to small-animal irradiation
      by making it compatible with the dimensions of mice and rats, modeling the
      microirradiator beam orientations and collimators, and incorporating the measured
      beam data for dose calculation. Dose calculations in Metropolis were verified by
      comparison with measurements in phantoms. Treatment plans for irradiation of a
      tumor-bearing mouse were generated with both the Metropolis and the vendor
      supplied software. The calculated beam-on times and the plan evaluation tools
      were compared. The dose rate at the central axis ranges from 74 to 365 cGy/min
      depending on the collimator size. Doses calculated with Metropolis agreed with
      phantom measurements within 3% for all collimators. The beam-on times calculated
      by Metropolis and the vendor-supplied software agreed within 1% at the isocenter.
      The modified 3-dimensional treatment planning system provides better
      visualization of the relationship between the X-ray beams and the small-animal
      anatomy as well as more complete dosimetric information on target tissues and
      organs at risk. It thereby enhances the potential of image-guided microirradiator
      systems for evaluation of dose-response relationships and for preclinical
      experimentation generally.

PMID- 25948322
TI  - Progress of Circulating Tumor Cells in Cancer Management.
AB  - Circulating tumor cells are low-frequency cells that are shed into the peripheral
      bloodstream from a primary solid tumor and/or metastasis. Although these cells
      were recognized initially in 1869, it is only in the past 2 decades that they
      have been isolated for use as a surrogate biomarker to monitor response to
      therapy, evaluate prognosis, detect tumor mutations, assist in selecting
      personalized medicine, and enable earlier cancer diagnosis.

PMID- 25948323
TI  - The Parotid Gland is an Underrecognized Organ at Risk for Craniospinal
      Irradiation.
AB  - PURPOSE: Current craniospinal irradiation (CSI) protocols do not include the
      parotid gland as an organ at risk, potentially leading to late effects of
      xerostomia and secondary parotid malignancies. We analyzed the effect of CSI
      treatment parameters on parotid dose. MATERIALS AND METHODS: We retrospectively
      reviewed 50 consecutive patients treated with CSI to an intracranial dose >26 Gy.
      Parotid dose was compared to a Radiation Therapy Oncology Group (RTOG) dose
      constraint (at least 1 parotid with mean dose <26 Gy). The effects of CSI dose
      (<=24 Gy vs 24 Gy), volumetric-modulated arc therapy (VMAT) versus 3-dimensional
      (3D) CSI technique, boost dose (<=24 Gy vs 24 Gy), supratentorial versus
      infratentorial boost location, intensity-modulated radiation therapy (IMRT)-based
      versus 3D boost technique, supine versus prone position, and age on parotid dose
      were analyzed using multivariate regression analysis. RESULTS: The RTOG parotid
      dose constraint was exceeded in 22 (44%) of 50 patients. On multivariate
      regression analysis, lower CSI dose and VMAT CSI technique were associated with
      reduced parotid dose for the CSI fields. For the boost fields, lower boost dose
      and supratentorial boost location were associated with lower parotid dose. All 5
      patients who underwent VMAT CSI met dose constraints. Furthermore, for
      infratentorial lesions with a total (CSI plus boost) dose prescription dose >50
      Gy (n = 24), 11 of 16 patients who received low-dose CSI (18-23.4 Gy) were able
      to meet dose constraints, when compared to only 2 of 8 patients who received high
      dose CSI (36 Gy). CONCLUSION: Given the large number of patients exceeding the
      parotid dose constraint, the parotid gland should be considered an organ at risk.
      CSI dose de-escalation and IMRT-based CSI techniques may minimize the risk of
      xerostomia.

PMID- 25948324
TI  - Physical characterization of meso-erythritol as a crystalline bulking agent for
      freeze-dried formulations.
AB  - The purpose of this study was to identify and characterize new crystalline
      bulking agents applicable to freeze-dried pharmaceuticals. Thermal analysis of
      heat-melt sugar and sugar alcohol solids as well as their frozen aqueous
      solutions showed high crystallization propensity of meso-erythritol and D
      mannitol. Experimental freeze-drying of the aqueous meso-erythritol solutions
      after their cooling by two different methods (shelf-ramp cooling and immersion of
      vials into liquid nitrogen) resulted in cylindrical crystalline solids that
      varied in appearance and microscopic structure. Powder X-ray diffraction and
      thermal analysis indicated different crystallization processes of meso-erythritol
      depending on the extent of cooling. Cooling of the frozen meso-erythritol
      solutions at temperatures lower than their Tg' (glass transition temperature of
      maximally freeze-concentrated phase, -59.7 degrees C) induced a greater number of
      nuclei in the highly concentrated solute phase. Growth of multiple meso
      erythritol anhydride crystals at around -40 degrees C explains the powder-like
      fine surface texture of the solids dried after their immersion in liquid
      nitrogen. Contrarily, shelf-ramp cooling of the frozen solution down to -40
      degrees C induced an extensive growth of the solute crystal from a small number
      of nuclei, leading to scale-like patterns in the dried solids. An early
      transition of the freezing step into primary drying induced collapse of the non
      crystalline region in the cakes. Appropriate process control should enable the
      use of meso-erythritol as an alternative crystalline bulking agent in freeze
      dried formulations. 

PMID- 25948325
TI  - Formation of the ternary inclusion complex of limaprost with alpha- and beta
      cyclodextrins in aqueous solution.
AB  - The inclusion mode of Limaprost in the presence of alpha- and beta-cyclodextrins
      (CDs) was investigated to gain insight into the stabilization mechanism of
      Limaprost-alfadex upon the addition of beta-CD in the solid state. The inclusion
      sites of alpha- and beta-CDs were studied by NMR spectroscopic and kinetic
      methods. With the addition of alpha- and beta-CDs, displacements in (13)C
      chemical shifts of prostaglandin F2alpha (PGF2alpha) were observed in the omega
      chain and the five-membered ring, respectively, of the drug. Similar shift
      changes were observed with the addition of both alpha- and beta-CDs. In two
      dimensional (2D) (1)H-NMR spectra, intermolecular correlation peaks were observed
      between protons of PGF2alpha and protons of both alpha- and beta-CDs, suggesting
      that PGF2alpha interacts with alpha- and beta-CDs to form a ternary complex by
      including the omega-chain with the former CD and the five-membered ring with the
      latter. In kinetic studies in aqueous solution, Limaprost was degraded to 17S,20
      dimethyl-trans-Delta(2)-PGA1 (11-deoxy-Delta(10)) and 17S,20-dimethyl-trans
      Delta(2)-8-iso-PGE1 (8-iso). The addition of alpha-CD promoted the dehydration to
      11-deoxy-Delta(10), while beta-CD promoted the isomerization to 8-iso, under
      these conditions. In the presence of both alpha- and beta-CDs, dehydration and
      isomerization were also accelerated, supporting the formation of the ternary
      Limaprost/alpha-CD/beta-CD complex. 

PMID- 25948326
TI  - Synthesis and biological evaluation of piperic acid amides as free radical
      scavengers and alpha-glucosidase inhibitors.
AB  - A series of piperic acid amides (4-24, 29, 30) were synthesized and their 1,1
      diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and alpha-glucosidase
      inhibitory activities were evaluated. Among the synthesized compounds, the amides
      11, 13 and 15, which contain o-methoxyphenol, catechol or 5-hydroxyindole
      moieties, showed potent DPPH free radical scavenging activity (11: EC50 140 uM;
      13: EC50 28 uM; 15: EC50 20 uM). The amides 10, 18 and 23 showed higher
      inhibitory activity of alpha-glucosidase (10: IC50 21 uM; 18: IC50 21 uM; 23:
      IC50 12 uM). These data suggest that the hydrophobicity of the conjugated amines
      is an important determinant of alpha-glucosidase inhibitory activity. In
      addition, the amides 13 and 15 showed both potent DPPH free radical scavenging
      activity and alpha-glucosidase inhibitory activity (13: IC50 46 uM; 15: IC50 46
      uM). This is the first report identifying the DPPH free radical scavenging and
      alpha-glucosidase inhibitory activities of piperic acid amides and suggests that
      these amides may serve as lead compounds for the development of novel alpha
      glucosidase inhibitors with antioxidant activity. 

PMID- 25948327
TI  - Glyceryl monooleyl ether-based liquid crystalline nanoparticles as a transdermal
      delivery system of flurbiprofen: characterization and in vitro transport.
AB  - Liquid crystalline nanoparticles (LCNs) were prepared using glyceryl monooleyl
      ether (GME) by the modified film rehydration method. Hydrogenated lecithin (HL),
      1,3-butylene glycol (1,3-BG), and Poloxamer 407 were used as additives. The
      prepared LCN formulations were evaluated based on particle size, small-angle X
      ray diffraction (SAXS) analysis, (1)H- and (19)F-NMR spectra, and in vitro skin
      permeation across Yucatan micropig skin. The composition (weight percent) of the
      LCN formulations were GME-HL-1,3-BG (4 : 1 : 15), 4% GME-based LCN and GME-HL-1,3
      BG (8 : 1 : 15), 8% GME-based LCN and their mean particle sizes were 130-175 nm.
      Flurbiprofen 5 and 10 mg was loaded into 4% GME-based LCN and 8% GME-based LCN
      systems, respectively. The results of SAXS and NMR suggested that both
      flurbiprofen-loaded formulations consist of particles with reverse type hexagonal
      phase (formation of hexosome) and flurbiprofen molecules were localized in the
      lipid domain through interaction of flurbiprofen with the lipid components.
      Flurbiprofen transport from the LCN systems across the Yucatan micropig skin was
      increased compared to flurbiprofen in citric buffer (pH=3.0). The 8% GME-based
      LCN systems was superior to the 4% GME-based LCN for flurbiprofen transport.
      Since the internal hexagonal phase in the 8% GME-based LCN systems had a higher
      degree of order compared to the 4% GME-based LCN in SAXS patterns, the 8% GME
      based LCN system had a larger surface area, which might influence flurbiprofen
      permeation. These results indicated that the GME-based LCN system is effective in
      improving the skin permeation of flurbiprofen across the skin. 

PMID- 25948328
TI  - Development of gummi drugs of aripiprazole as hospital formulations.
AB  - About half of patients with schizophrenia have poor adherence to taking
      medication, so many have recurrence, therefore, providing formulations that
      enable patients to continue their medication without interruption is important.
      We aimed to develop a gummi drug that contains aripiprazole (which can reduce
      schizophrenia and manic symptoms in bipolar disorder). We were able to develop
      gummi drugs (OD-G, PW-G and OS-G) using three commercially available aripiprazole
      products (Abilify(r) orally disintegrating tablets, powder formulation, and oral
      solutions, respectively) as hospital formulations. Furthermore, we developed
      improved OD-G (iOD-G), which contained high aripiprazole content. Pharmaceutical
      characteristics of iOD-G were demonstrated to be suitable for hospital
      formulations, and iOD-G could be stored for <=1 month. No significant differences
      in the dissolution and pharmacokinetics of divided portions of iOD-G were
      observed when compared with commercially available aripiprazole products. This
      study confirmed that new dosage forms of aripiprazole in gummi drugs can be
      developed as hospital formulations, which will contribute to improve medication
      adherence of patients. 

PMID- 25948329
TI  - Ginsenoside Rg3 bile salt-phosphatidylcholine-based mixed micelles: design,
      characterization, and evaluation.
AB  - 20(R)-Ginsenoside Rg3 (G-Rg3) has good inhibition of tumor angiogenesis and anti
      tumor effect. However, its poor aqueous solubility and liposolubility are not
      ideal for clinical applications. In this study, a G-Rg3 bile salt
      phosphatidylcholine-based mixed micelle system (BS-PC-MMS) was prepared. The
      optimization of G-Rg3 BS-PC-MMS was carried out using response surface
      methodology based on a central composite design. The encapsulation efficiency
      (EE) and light transmission (LT) of the optimized formulation were 90.69+/-2.54%
      and 99.10+/-3.12%, respectively. The average particle size of micelles was 20 nm.
      To increase the stability of G-Rg3 BS-PC-MMS, the lyophilized formulation of
      micelles was prepared. The G-Rg3 BS-PC-MMS did not produce hemolysis of
      erythrocytes within a certain concentration range and exhibited a good inhibition
      of tumor cells. The chick embryo chorioallantoic membrane assay results showed
      that the G-Rg3 BS-PC-MMS significantly inhibited angiogenesis. The G-Rg3 BS-PC
      MMS is thus shown to be a safe, stable, and promising drug delivery system. 

PMID- 25948331
TI  - Magnetic resonance imaging of the phase separation in mixed preparations of
      moisturizing cream and steroid ointment after centrifugation.
AB  - A mixed preparation consisting of a water-in-oil emulsion-type moisturizing cream
      and a steroid ointment is frequently prescribed for the treatment of atopic
      dermatitis. We have investigated the compatibility of moisturizing creams and
      ointments because there are concerns regarding the physical stability of these
      mixed preparations. The key technology used in this study was magnetic resonance
      imaging (MRI). A commercial moisturizing cream and white petrolatum or
      clobetasone butyrate (CLB) ointment samples were mixed in a weight ratio of 1 :
      1. A centrifugation test protocol (20000*g for 3 min) was implemented to
      accelerate the destabilization processes in the samples. After centrifugation,
      the mixed preparations separated into three distinct layers (upper, middle, and
      lower), while no phase separation was observed using moisturizing cream alone.
      The phase separation was monitored using chemical shift selective images of water
      and oil and quantitative T2 maps. In addition, MR and near-infrared spectroscopy
      were employed for component analysis of each phase-separated layer. Collectively,
      it was confirmed that the lower layer contained water, oils, and organic solvent,
      while the upper and middle layers were composed solely of oils. Furthermore, this
      study investigated the distribution of CLB in the phase-separated samples and
      showed that a heterogeneous distribution existed. From our results, it was
      confirmed that the mixed preparation became unstable because of the
      incompatibility of the moisturizing cream and ointment. 

PMID- 25948330
TI  - Synthesis and anticancer evaluation of 1,3,4-oxadiazoles, 1,3,4-thiadiazoles,
      1,2,4-triazoles and Mannich bases.
AB  - A series of 5-(pyridin-4-yl)-N-substituted-1,3,4-oxadiazol-2-amines (3a-d), 5
      (pyridin-4-yl)-N-substituted-1,3,4-thiadiazol-2-amines (4a-d) and 5-(pyridin-4
      yl)-4-substituted-1,2,4-triazole-3-thiones (5a-d) were obtained by the
      cyclization of hydrazinecarbothioamide derivatives 2a-d derived from isonicotinic
      acid hydrazide. Aminoalkylation of compounds 5a-d with formaldehyde and various
      secondary amines furnished the Mannich bases 6a-p. The structures of the newly
      synthesized compounds were confirmed on the basis of their spectral data and
      elemental analyses. All the compounds were screened for their in vitro anticancer
      activity against six human cancer cell lines and normal fibroblast cells. Sixteen
      of the tested compounds exhibited significant cytotoxicity against most cell
      lines. Among these derivatives, the Mannich bases 6j, 6m and 6p were found to
      exhibit the most potent activity. The Mannich base 6m showed more potent
      cytotoxic activity against gastric cancer NUGC (IC50=0.021 uM) than the standard
      CHS 828 (IC50=0.025 uM). Normal fibroblast cells WI38 were affected to a much
      lesser extent (IC50>10 uM). 

PMID- 25948332
TI  - Geranylated flavanones from Paulownia coreana and their inhibitory effects on
      nitric oxide production.
AB  - The activity-guided fractionation of the MeOH extract of the flower of Paulownia
      coreana led to the isolation of a new geranylated flavanone, 3'-O-methyl-5'
      hydroxydiplacol (1), along with 10 known compounds (2-11). Their structures were
      determined using spectroscopic techniques, which included one and two dimensional
      (1- and 2D)-NMR. Among the isolates, compounds 1-6 showed potent inhibitory
      activities against lipopolysaccharide (LPS)-induced nitric oxide production with
      IC50 values ranging 1.48 to 16.66 uM. 

PMID- 25948333
TI  - Synthesis of alkynes from vinyl triflates using tetrabutylammonium fluoride.
AB  - A convenient method for the preparation of alkynes and alkynyl esters from
      ketones and beta-keto esters is described which involves the formation of vinyl
      triflates, followed by elimination with tetrabutylammonium fluoride trihydrate,
      to give alkynes. Unlike established elimination methods, the method requires
      neither a strong base nor anhydrous conditions. 

PMID- 25948334
TI  - Positron annihilation lifetime spectroscopy (PALS): a probe for molecular
      organisation in self-assembled biomimetic systems.
AB  - Positron annihilation lifetime spectroscopy (PALS) has been shown to be highly
      sensitive to conformational, structural and microenvironmental transformations
      arising from subtle geometric changes in molecular geometry in self-assembling
      biomimetic systems. The ortho-positronium (oPs) may be considered an active probe
      that can provide information on intrinsic packing and mobility within low
      molecular weight solids, viscous liquids, and soft matter systems. In this
      perspective we provide a critical overview of the literature in this field,
      including the evolution of analysis software and experimental protocols with
      commentary upon the practical utility of PALS. In particular, we discuss how PALS
      can provide unique insight into the macroscopic transport properties of several
      porous biomembrane-like nanostructures and suggest how this insight may provide
      information on the release of drugs from these matrices to aid in developing
      therapeutic interventions. We discuss the potentially exciting and fruitful
      application of this technique to membrane dynamics, diffusion and permeability.
      We propose that PALS can provide novel molecular level information that is
      complementary to conventional characterisation techniques. 

PMID- 25948335
TI  - Deep convolutional neural networks for annotating gene expression patterns in the
      mouse brain.
AB  - BACKGROUND: Profiling gene expression in brain structures at various spatial and
      temporal scales is essential to understanding how genes regulate the development
      of brain structures. The Allen Developing Mouse Brain Atlas provides high
      resolution 3-D in situ hybridization (ISH) gene expression patterns in multiple
      developing stages of the mouse brain. Currently, the ISH images are annotated
      with anatomical terms manually. In this paper, we propose a computational
      approach to annotate gene expression pattern images in the mouse brain at various
      structural levels over the course of development. RESULTS: We applied deep
      convolutional neural network that was trained on a large set of natural images to
      extract features from the ISH images of developing mouse brain. As a baseline
      representation, we applied invariant image feature descriptors to capture local
      statistics from ISH images and used the bag-of-words approach to build image
      level representations. Both types of features from multiple ISH image sections of
      the entire brain were then combined to build 3-D, brain-wide gene expression
      representations. We employed regularized learning methods for discriminating gene
      expression patterns in different brain structures. Results show that our approach
      of using convolutional model as feature extractors achieved superior performance
      in annotating gene expression patterns at multiple levels of brain structures
      throughout four developing ages. Overall, we achieved average AUC of 0.894 +/-
      0.014, as compared with 0.820 +/- 0.046 yielded by the bag-of-words approach.
      CONCLUSIONS: Deep convolutional neural network model trained on natural image
      sets and applied to gene expression pattern annotation tasks yielded superior
      performance, demonstrating its transfer learning property is applicable to such
      biological image sets.

PMID- 25948336
TI  - Nile red fluorescence screening facilitating neutral lipid phenotype
      determination in budding yeast, Saccharomyces cerevisiae, and the fission yeast
      Schizosaccharomyces pombe.
AB  - Investigation of yeast neutral lipid accumulation is important for biotechnology
      and also for modelling aberrant lipid metabolism in human disease. The Nile red
      (NR) method has been extensively utilised to determine lipid phenotypes of yeast
      cells via microscopic means. NR assays have been used to differentiate lipid
      accumulation and relative amounts of lipid in oleaginous species but have not
      been thoroughly validated for phenotype determination arising from genetic
      modification. A modified NR assay, first described by Sitepu et al. (J Microbiol
      Methods 91:321-328, 2012), was able to detect neutral lipid changes in
      Saccharomyces cerevisiae deletion mutants with sensitivity similar to more
      advanced methodology. We have also be able to, for the first time, successfully
      apply the NR assay to the well characterised fission yeast Schizosaccharomyces
      pombe, an increasingly important organism in biotechnology. The described NR
      fluorescence assay is suitable for increased throughput and rapid screening of
      genetically modified strains in both the biotechnology industry and for modelling
      ectopic lipid production for a variety of human diseases. This ultimately negates
      the need for labour intensive and time consuming lipid analyses of samples that
      may not yield a desirable lipid phenotype, whilst genetic modifications impacting
      significantly on the cellular lipid phenotype can be further promoted for more in
      depth analyses. 

PMID- 25948337
TI  - Selective chemical modification of DNA with alkoxy- and benzyloxyamines.
AB  - A new method for the selective chemical modification of DNA at cytosine
      nucleobases using alkoxy- and benzyloxyamines is presented. It is shown that in
      particular benzyloxyamines are effective DNA modifying agents, giving rise to
      almost exclusive formation of the mono addition products. By using a bifunctional
      derivative, that is, p-azidobenzyloxyamine hydrochloride, an azide moiety, which
      is a convenient handle for further functionalization, could be introduced into
      the DNA. The azido modified DNA was then further reacted in a copper(I)-monophos
      catalysed 1,3-dipolar cycloaddition. These results illustrate the potential of
      the presented method for application in site and chemo-selective modification of
      DNA.

PMID- 25948338
TI  - A nationwide cross-sectional study on congenital heart diseases and symptoms of
      sleep-disordered breathing among Japanese Down's syndrome people.
AB  - OBJECTIVE: It is well known that people with Down's syndrome (DS) frequently
      complicate with congenital heart diseases (CHDs). Patients with heart diseases
      often have sleep-disordered breathing as a co-morbidity (SDB) which worsens the
      heart diseases. However, the relationship between SDB and CHDs in DS people has
      not yet been fully elucidated. The aim of this study was to establish the
      association between SDB and CHDs in DS people using data from a large nationwide
      questionnaire survey in Japan. METHODS: We conducted a cross-sectional
      questionnaire survey of a randomly selected sample of 2,000 DS people and their
      caregivers throughout Japan to examine the associations between observed signs of
      SDB and CHDs in DS people. The questionnaire included the presence of SDB
      symptoms (snoring, apnea, arousal, nocturia, and napping) and CHDs (the presence
      and types of CHDs). RESULTS: Of the 1,222 replies received from the caregivers,
      650 reported complications of some type of CHDs. The observed apnea tended to be
      higher among DS people with CHDs than those without CHDs (OR=1.28, 95% CI=0.97
      1.70, p=0.09). DS people with tetralogy of Fallot reported significantly more
      frequent apnea than those without CHDs (OR=3.10, 95% CI=1.36-7.05, p<0.01).
      CONCLUSION: SDB prevailed among DS people with severe CHDs, such as tetralogy of
      Fallot. Careful attention to the signs of SDB in such patients may lead to
      earlier clinical intervention removing the vicious cycle between SDB and CHDs.

PMID- 25948339
TI  - Epicardial fat thickness in patients with prediabetes and correlation with other
      cardiovascular risk markers.
AB  - OBJECTIVE: Prediabetes is a condition between a normal metabolic state and
      diabetes mellitus, which includes impaired glucose tolerance (IGT), impaired
      fasting glucose (IFG), or both. Prediabetes is related with undesirable
      cardiovascular outcomes. Epicardial fat thickness (EFT) has been correlated with
      cardiovascular risk factors. We herein aimed to assess EFT in prediabetic
      patients. METHODS: We evaluated 64 patients with prediabetes and 30 age- and
      gender-matched healthy subjects. Demographic and anthropometric characteristics
      [age, sex, height, weight, body mass index (BMI), and waist circumference (WC)]
      and laboratory findings [fasting plasma glucose (FPG), postprandial plasma
      glucose (PPG), hemoglobin A1c (HbA1c), low density lipoprotein (LDL), high
      density lipoprotein (HDL), and triglycerides (TG)] were assessed. Transthoracic
      echocardiography was used to evaluate EFT. RESULTS: There were no significant
      differences between the case and control groups in terms of age, gender, height,
      HDL, WC, systolic and diastolic blood pressure (SBP/DBP), or TG (p>0.05). Body
      weight, BMI, FPG, LDL, and, in particular, EFT were found to be significantly
      higher in the case group than control group (p<0.05). When compared with the
      control group, the median EFT was significantly higher in all prediabetic
      subgroups (IGT or IFG, p<0.001). However, no statistically significant difference
      was found between each case subgroup (p=0.795). When groups were adjusted
      according to age, sex, WC, and BMI with covariance test, the EFT remained
      increased in the prediabetes subgroups compared to the controls (p<0.001).
      CONCLUSION: We found the EFT levels to be increased in all subgroups of
      prediabetic patients regardless of FPG and HbA1c. Furthermore, EFT directly
      correlated with the patients' BMI and WC.

PMID- 25948340
TI  - Serum torque teno virus DNA titer in idiopathic pulmonary fibrosis patients with
      acute respiratory worsening.
AB  - OBJECTIVE: Acute respiratory worsening is defined as the unexpected rapid
      deterioration of idiopathic pulmonary fibrosis (IPF), and idiopathic acute
      respiratory worsening is known as an acute exacerbation of IPF. Torque teno virus
      (TTV) is a circular single-stranded DNA virus whose pathological significance
      remains unclear. The aim of the present study was to investigate the prevalence
      and titer of TTV DNA in IPF patients with acute respiratory worsening. METHODS:
      The serum TTV DNA titer was measured using real-time PCR in nine IPF patients
      (two treated with steroids and immunosuppressants; seven treated without steroids
      or immunosuppressants) who developed acute worsening, including five patients
      with acute exacerbation. The serum TTV DNA titer was also measured in eight
      stable IPF cases and four IPF cases of lung cancer. In addition, in order to
      examine time course changes in the TTV DNA titer, the titer was measured more
      than once, with an interval of four weeks or longer, in eight patients. RESULTS:
      Among the nine IPF patients with acute worsening, the TTV DNA titer was above
      1*10(6) copies/mL in two subjects without acute exacerbation who had been
      continuously treated with steroids and immunosuppressants. Meanwhile, the mean
      TTV DNA titer was 2.4+/-2.6 (*10(4) copies/mL) in the five patients with acute
      exacerbation and 3.1+/-3.4 (*10(4) copies/mL) in the eight patients with stable
      IPF. Moreover, the TTV DNA titers were increased in all three IPF patients who
      started treatment with steroids and immunosuppressants. CONCLUSION: Our results
      suggest that it is unlikely that TTV is directly involved in the onset of acute
      exacerbation of IPF and that the serum TTV DNA titer potentially reflects the
      immunosuppressive state of the host due to treatment.

PMID- 25948341
TI  - Virtual bronchoscopic navigation improves the diagnostic yield of radial
      endobronchial ultrasound for peripheral pulmonary lesions with involved bronchi
      on CT.
AB  - OBJECTIVE: Bronchoscopy using radial-endobronchial ultrasound (R-EBUS) and
      virtual bronchoscopic navigation (VBN) is a promising method for diagnosing
      peripheral pulmonary lesions. We previously performed a randomized comparative
      trial (RCT) (i.e., VBN combined with EBUS RCT) involving patients with 30-mm or
      smaller peripheral pulmonary lesions and found that the addition of VBN to R-EBUS
      improved the diagnostic yield. In the present study, we performed a retrospective
      subanalysis in order to identify patients for whom VBN is useful. METHODS: The
      per-protocol population (194 cases) of the VBN combined with EBUS RCT was divided
      into subgroups based on the lesion size, lung lobe containing the lesion, lesion
      location, presence or absence of involved bronchi (bronchus sign) on thin-section
      CT and whether the lesion was detected on posterior-anterior (P-A) radiographs.
      The difference in the diagnostic yield between the VBN-assisted (VBNA) and non
      VBN-assisted (NVBNA) groups was investigated. RESULTS: Within the bronchus sign
      positive subgroup, the diagnostic yield in the VBNA and NVBNA groups was 94.4%
      (68/72) and 77.8% (56/72), respectively, showing a significantly higher yield in
      the VBNA group (p=0.004; odds ratio: 4.9). The yield was particularly high for
      lesions smaller than 20 mm (94.6% vs. 70.7%; p=0.006), lesions located in the
      peripheral third of the lung field (95.1% vs. 71.4%; p=0.005) and lesions
      invisible on P-A radiographs (90.0% vs. 41.7%; p=0.026). CONCLUSION: VBN improves
      the diagnostic yield when combined with R-EBUS to assess lesions exhibiting
      involved bronchi on CT images.

PMID- 25948342
TI  - Analysis of cerebral lobar microbleeds and a decreased cerebral blood flow in a
      memory clinic setting.
AB  - OBJECTIVE: Cerebral microbleeds (MBs) have been previously associated with
      cognitive dysfunction, including Alzheimer's disease. In the present study, we
      aimed to clarify the relationship between cerebral lobar MBs and the regional
      cerebral blood flow (CBF). METHODS: We investigated the data obtained from 122
      patients in our memory clinic who were examined by both MRI and (99m)Tc-ethyl
      cysteinate dimer (ECD)-single photon emission computed tomography (SPECT).
      Patient brain scans were superimposed and brain regions containing both decreased
      CBF and MBs were visually identified. For each patient eight brain regions were
      evaluated, comprising the right and left frontal, temporal, parietal, and
      occipital lobes. RESULTS: Cerebral MBs were detected in 36 of the 122 (29.5%)
      patients. Of these 36 patients, 23 had detectable lobar MBs, which were primarily
      distributed in the occipital lobe in 19 of the 46 (41.3%) regions with lobar MBs.
      The frequency of MBs accompanied by a decreased CBF in the parietal and occipital
      lobes was significantly higher than that observed in the frontal lobe (73.3% vs.
      27.3%, p<0.05, and 73.7% vs. 27.3%, p<0.05, respectively). Additionally, a
      decreased CBF was observed significantly more frequently in the brain regions
      with 5 or more MBs compared to the regions with one microbleed (83.3 vs. 25.0%,
      p<0.0005). Among the 17 patients with observable MBs accompanied by a decreased
      CBF, none were initially diagnosed with either subjective complaints or mild
      cognitive impairment. CONCLUSION: We determined that the cerebral lobar MBs
      located in the parietal and occipital lobes, and the lobar regions with a large
      number of MBs, were significantly more likely to be accompanied by a decreased
      CBF.

PMID- 25948343
TI  - The rate of decrease in the disease activity of rheumatoid arthritis during
      treatment with adalimumab depends on the dose of methotrexate.
AB  - OBJECTIVE: The aim of this study was to analyze the efficacy of adalimumab (ADA)
      in patients with rheumatoid arthritis treated with or without methotrexate (MTX)
      and determine impact of the MTX dose. METHODS: Pearson's product-moment
      correlation coefficient was used to assess the correlations between the
      improvement in the Disease Activity Score (DAS) 28- erythrocyte sedimentation
      rate (ESR) score and the MTX dose in patients receiving treatment with MTX at a
      dose of <8 mg/week, 8 mg/week and >8 mg/week. PATIENTS: ADA therapy was initiated
      in 68 rheumatoid arthritis patients between July 2008 and June 2013. The mean MTX
      dose was 9.6 +/- 2.6 mg/week, and the patients were followed for 24 weeks.
      RESULTS: The mean DAS28-ESR scores at baseline and week 24 were 4.6 +/- 1.3 and
      2.7 +/- 1.2 in the 60 patients treated with MTX and 4.5 +/- 1.0 and 4.2 +/- 1.5
      in the eight patients treated without MTX, respectively. Clinical remission was
      achieved in 48% and 25% of the patients, respectively, by week 24. Moreover,
      90.0% of the patients taking MTX continued to receive ADA until week 24, while
      50.0% of the patients not taking MTX continued to receive ADA until week 24.
      Among the 35 patients receiving MTX at a dose of >8 mg/week, the DAS28-ESR scores
      decreased rapidly from 4.4 +/- 1.2 at baseline to 3.2 +/- 1.1 at week 4 and
      further decreased to 2.4 +/- 1.0 at week 24. Meanwhile, clinical remission was
      achieved in 57% of the patients receiving MTX at a dose of >8 mg/week and 36% of
      those receiving MTX at a dose of <=8 mg/week. A significant correlation was noted
      between the improvement in the DAS-ESR score and the MTX dose. CONCLUSION: In
      this study population, enhanced clinical efficacy of ADA was achieved in
      combination with the administration of a sufficient dose of MTX, determined to be
      >8 mg/week.

PMID- 25948344
TI  - Obstructive uropathy caused by chronic constipation.
AB  - We herein report a case regarding a 90-year-old woman with a history of recurrent
      episodes of urinary tract infections presenting with fever. Urinalysis revealed
      bacteria and white blood cells. Computed tomography showed dilated and fecally
      loaded rectum and colon with signs of obstructive uropathy. The patient was
      treated for urinary tract infection and constipation. Her bowel habits were
      controlled with lubiprostone, and she was discharged in good medical condition.
      This case highlights the importance of considering fecal impaction as a cause of
      urinary tract obstruction or infection. 

PMID- 25948345
TI  - Temporary insertion of a covered self-expandable metal stent to treat esophageal
      perforation due to endoscopic submucosal dissection.
AB  - There are no previous reports of esophageal perforation due to endoscopic
      submucosal dissection developing into pyothorax. We herein describe a case of
      esophageal healing following perforation in a 60-year-old woman undergoing
      esophageal endoscopic submucosal dissection. Post-procedural computed tomography
      revealed pyothorax in the right thoracic cavity, compressing the right lung. The
      pyothorax did not improve despite treatment with thoracic drainage because the
      esophageal lumen was connected to the right thoracic cavity. In order to close
      the site of esophageal perforation, we inserted a covered self-expandable metal
      stent. The affected site subsequently healed without complications, allowing the
      drainage tube and stent to be removed. 

PMID- 25948346
TI  - Anomalous origin of the left circumflex artery from the right sinus of valsalva:
      non-ST-segment elevation myocardial infarction.
AB  - An anomalous origin of the left coronary artery from the right sinus of Valsalva
      (RSV) is rare. We herein report the case of an 80-year-old woman who presented to
      the emergency department with chest pain. Emergent coronary angiography was
      performed following a diagnosis of non-ST segment elevation myocardial
      infarction. A right coronary angiogram showed that the common trunk originating
      from the RSV branched into the left anterior descending and right coronary
      arteries. Although the initial angiogram failed to show the left circumflex
      artery (LCx), considered to be the culprit vessel, computed tomographic
      angiography demonstrated that the LCx was located immediately below the common
      trunk and exhibited a retroaortic course. We successfully treated the patient and
      obtained optimal angiography results. 

PMID- 25948347
TI  - A rare case of acute myocardial infarction with multivessel coronary artery
      ectasia successfully treated with percutaneous coronary intervention and systemic
      thrombolysis.
AB  - Coronary artery ectasia (CAE) is defined as a coronary artery dilatation with a
      diameter >=1.5 times greater than that of a normal adjacent artery. All 3
      coronary vessels can be affected by CAE, but the incidence of multivessel CAE
      among patients undergoing coronary angiography is quite low. We herein report an
      extremely rare case of acute myocardial infarction due to massive thrombi in the
      giant right coronary artery with multivessel CAE. Thrombus aspiration during
      percutaneous coronary intervention may be limited in giant coronary artery cases,
      and systemic thrombolysis may be effective in patients with massive thrombi in
      the giant coronary artery. 

PMID- 25948348
TI  - Uncommon presentation of drug-refractory pacemaker-mediated common
      atrioventricular nodal reentrant tachycardia and a simple solution by
      reprogramming.
AB  - An 81-year-old woman who had undergone dual chamber pacemaker implantation for
      sick sinus syndrome was referred to our hospital with drug-refractory common
      atrioventricular (AV) nodal reentrant tachycardia. Ventricular pacing (Vp)
      following premature atrial contraction (PAC) with a long AV interval induced
      ventriculoatrial (VA) conduction, which allowed the tachycardia to be initiated.
      The sensed AV interval was shortened to 80 ms, allowing Vp during the refractory
      period of VA conduction. Postventricular atrial refractory period was shortened
      to 180 ms to sense PACs with short coupling interval. After reprogramming, the
      suppression of the tachycardia by blocking VA conduction following Vp was
      confirmed. 

PMID- 25948349
TI  - Platypnea-orthodeoxia syndrome: an unusual complication of partial liver
      resection.
AB  - Platypnea-orthodeoxia syndrome (POS) is a rare syndrome of severe hypoxemia upon
      assuming an upright position. It is classically described as shunting from the
      right atrium to the left atrium usually via a patent foramen ovale (PFO).
      Alterations in the intrathoracic anatomy after liver resection and regeneration
      may trigger this condition in patients with clinically silent PFO -a previously
      unreported cause of POS. 

PMID- 25948350
TI  - An adult case of polysplenia syndrome associated with sinus node dysfunction,
      dextrocardia, and systemic venous anomalies.
AB  - A 54-year-old woman was referred to our hospital for symptomatic sinus
      bradyarrhythmia with a sinus pause of 8 seconds. She was diagnosed with
      dextrocardia during childhood and discovered to have heterotaxy syndrome when she
      had an appendectomy during her teenager years. Chest and abdominal examinations
      by computed tomography showed multiple spleens located on the right side and
      abnormal drainages of the superior and inferior vena cava. Left isomerism was
      diagnosed by bilaterally bilobed lungs. Because of a patent bilateral superior
      vena cava, pacemaker leads were implanted using the right cephalic vein approach.
      Her fainting symptoms disappeared after pacemaker implantation. 

PMID- 25948351
TI  - Takayasu arteritis and ulcerative cutaneous sarcoidosis.
AB  - A 67-year-old woman was referred to our hospital due to a refractory lower
      extremity ulcer. Occlusion of the bilateral superficial femoral arteries and a
      difference (>50 mmHg) in blood pressure between the bilateral upper limbs were
      noted. In addition to occlusion of the left subclavian artery and stenosis at the
      ostium of the right coronary artery, these findings led to a diagnosis of
      Takayasu arteritis. Furthermore, a biopsy of the ulcerated skin lesion localized
      on the fibular surface showed a non-caseating cutaneous granulomatous lesion
      resulting in the diagnosis of cutaneous sarcoidosis. The simultaneous occurrence
      of cutaneous sarcoidosis and Takayasu arteritis, albeit rare, should not be
      overlooked. 

PMID- 25948352
TI  - Membranous nephropathy with solitary immunoglobulin A deposition.
AB  - A 71-year-old woman was admitted with nephrotic syndrome. Light and electron
      microscopic analyses of renal biopsy tissue showed typical diffuse membranous
      features. In contrast, granular deposition of immunoglobulin A (IgA), but not
      IgG, IgM, C3 or C1q, was observed along the capillary walls on
      immunofluorescence. The patient was pathologically diagnosed with diffuse
      membranous nephropathy with solitary IgA deposition. Secondary membranous
      nephropathy was suspected; however, no underlying cause was found. The clinical
      and pathological findings, except for those of immunofluorescence, were all
      compatible with a diagnosis of primary membranous nephropathy. This is the first
      reported case of membranous nephropathy associated with solitary IgA deposition. 

PMID- 25948353
TI  - IgA nephropathy and psoriatic arthritis that improved with steroid pulse therapy
      and mizoribine in combination with treatment for chronic tonsillitis and
      epipharyngitis.
AB  - A 65-year-old man was admitted to our hospital with edema and renal dysfunction.
      He had received a diagnosis of psoriatic arthritis at 50 years of age. As a renal
      biopsy showed IgA nephropathy (IgAN), bilateral tonsillectomy was performed, and
      one course of steroid pulse therapy with an oral steroid and mizoribine were
      subsequently administered. The patient's proteinuria gradually reduced in
      association with an improvement in the renal function. In addition, the rash and
      arthralgia were ameliorated. In this case, adding treatment for chronic
      epipharyngitis accelerated the curative effects, and focal infection therapy
      consisting of immunosuppressive drugs was effective for both IgAN and psoriatic
      arthritis. 

PMID- 25948354
TI  - Hypereosinophilic obliterative bronchiolitis clinically mimicking diffuse
      panbronchiolitis: four-year follow-up.
AB  - A 73-year-old man with a known history of asthma presented with dyspnea,
      worsening wheezing and a productive cough complicated by chronic sinusitis. Chest
      computed tomography showed bronchial wall thickening with centrilobular nodules
      and ground-glass opacity in the right lower lobe. Features meeting the diagnostic
      criteria for diffuse panbronchiolitis (DPB) were identified, and lobectomy
      confirmed the presence of lung cancer. Over the subsequent four years, the
      patient's symptoms worsened. We reevaluated a lung lobe specimen, which showed
      hypereosinophilic obliterative bronchiolitis (HOB). A transbronchial lung biopsy
      also indicated bronchitis with eosinophilic infiltration. Our initial diagnosis
      of DPB was subsequently changed to HOB after four years. We herein describe this
      case of HOB, which was initially diagnosed as DPB primarily based on high
      resolution computed tomography, with a focus on the histopathology and long-term
      clinical course. This is the first report to document the long-term clinical
      course of HOB. 

PMID- 25948355
TI  - Intravascular synovial sarcoma of the pulmonary artery with massive pleural
      effusion: report of a case with a favorable response to Ifosfamide chemotherapy
      and palliative radiation therapy.
AB  - Synovial sarcoma (SS) commonly arises in the para-articular soft tissue; however,
      very few cases of intravascular SS have so far been reported. We herein describe
      a case of pulmonary artery SS with massive pleural effusion. A biopsy of the
      pleural lesions showed uniform short spindle cell proliferation, while the SYT
      SSX fusion gene, which is preceded by chromosomal translocation t(X;18)(p11;q11),
      was detected using reverse transcription-polymerase chain reaction. Treatment
      with ifosfamide chemotherapy and palliative radiation therapy was effective in
      reducing the growth of the tumor in the pulmonary artery and pleural lesions,
      indicating that this regimen may be useful for the treatment of unresectable SS
      in the pulmonary artery. 

PMID- 25948356
TI  - Chronological assessment of airway lesions in relapsing polychondritis by
      positron emission tomography.
AB  - A 40-year old woman presented with pyrexia, productive cough, and bilateral
      precordial pain. Positron emission tomography (PET)-computed tomography (CT)
      showed high, diffuse F-18 deoxyglucose accumulation in the tracheal,
      peribronchial, and bilateral costal cartilage. We diagnosed her with relapsing
      polychondritis (RP) based on McAdam's criteria. Airway lesions are a major
      prognostic indicator of RP, and so chronological assessment and control is
      essential. In this patient, PET-CT accurately reflected both the location and
      severity of the inflammation and helped to guide treatment decision-making and
      facilitated early detection of recurrence. However, its high cost is prohibitive
      to frequent use, making it necessary to comprehensively evaluate serum C-reactive
      protein levels, bronchoscopy, spirometry, and 3D-CT. 

PMID- 25948357
TI  - Autoimmune hemolytic anemia during adalimumab treatment for plaque psoriasis.
AB  - Adalimumab is commonly used to treat autoimmune diseases with few reported
      hematological adverse reactions. We herein describe the case of an 85-year-old
      Japanese man with plaque psoriasis who developed autoimmune hemolytic anemia
      (AIHA) after 3 years of adalimumab treatment. The patient suddenly developed
      hematuria and dyspnea on exertion while receiving adalimumab treatment.
      Laboratory data showed low hemoglobin levels and slightly increased reticulocyte
      counts, while direct and indirect antiglobulin tests were positive. The patient
      was diagnosed with AIHA which resolved after replacing the adalimumab treatment
      with prednisolone therapy. The findings from this case indicate that AIHA may be
      caused by long-term adalimumab treatment. 

PMID- 25948358
TI  - Human T-lymphotropic virus type-I (HTLV-I)-associated myelopathy with bulbar
      palsy-type amyotrophic lateral sclerosis-like symptoms.
AB  - We herein report a case of Human T-lymphotropic virus type-I (HTLV-I)-associated
      myelopathy with bulbar palsy-type amyotrophic lateral sclerosis-like symptoms. A
      52-year-old woman developed dyslalia at approximately 40 years of age, which
      slowly progressed. She presented with muscular atrophy and increased tendon
      reflexes of the extremities as well as bulbar palsy, from which motor neuron
      disease was suspected. Cerebrospinal fluid (CSF) testing revealed no
      abnormalities except for an elevated neopterin concentration at 143.17 pmol/mL
      (normal <=30 pmol/mL). Her serum and CSF anti-HTLV-I antibody titers were also
      high. Intravenous infusions of methylprednisolone decreased the CSF neopterin
      concentration to 50.33 pmol/mL. Subsequent oral prednisolone therapy was
      effective in alleviating the symptoms. 

PMID- 25948359
TI  - Demyelinating hypertrophic inferior alveolar nerve mimicking a nerve tumor.
AB  - We herein report a patient with demyelinating inferior alveolar nerve
      hypertrophy, which was initially suspected to have a nerve tumor. A 39-year-old
      woman with childhood-onset polyneuropathy presented with tooth pain and visited a
      dental clinic. An X-ray examination of the mandible revealed enlargement of the
      mandibular canal, and a nerve tumor was suspected. CT scan and MRI showed
      hypertrophy of the inferior alveolar nerve along its entire length. We diagnosed
      the patient with chronic inflammatory demyelinating polyradiculoneuropathy
      (CIDP), which was supported by the spontaneous recovery reported in her
      childhood, the results from a nerve conduction study and MRI data. CIDP should be
      considered in the differential diagnosis of mandibular canal enlargement. 

PMID- 25948360
TI  - Hemodialysis-related portal-systemic encephalopathy.
AB  - Hemodialysis-related portal-systemic encephalopathy (HRPSE) is characterized by
      the presence of portosystemic encephalopathy without liver dysfunction, usually
      caused by changes in the systemic venous flow related to hemodialysis. We herein
      describe the case of a 75-year-old woman who developed hepatic encephalopathy
      five years after the initiation of hemodialysis. Abdominal contrast-enhanced
      computed tomography (CT) and three-dimensional CT angiography revealed a
      portosystemic venous shunt, and the patient was diagnosed with portosystemic
      encephalopathy. Occlusion therapy ameliorated her disturbance of consciousness.
      HRPSE should be recognized as a treatable neuropsychiatric disorder. 

PMID- 25948361
TI  - Bortezomib in type I cryoglobulinemic vasculitis: are we acting too late?
AB  - Type II and type III cryoglobulinemic vasculitis (CV) are characterized by a
      deranged immune function due to concomitant chronic infections or rheumatic
      disorders. Conversely, type I CV is caused by plasma cell dyscrasia. Bortezomib
      is a proteasome inhibitor that is largely employed as a first-line treatment for
      multiple myeloma. The use of bortezomib in cases of monoclonal gammopathy of
      undetermined significance (MGUS)-related refractory type I CV has been reported
      in only four patients. In the current report, we discuss the efficacy of
      bortezomib treatment in a patient with type I CV, with a focus on the suitability
      and early application of this drug. 

PMID- 25948362
TI  - Fatal complication of Legionella pneumophila pneumonia in a tocilizumab-treated
      rheumatoid arthritis patient.
AB  - We herein report a fatal case of Legionella pneumophila pneumonia in a
      tocilizumab-treated rheumatoid arthritis patient who was in a state of shock on
      admission but remained afebrile even during severe pneumonia. Legionella antigen
      was detected in the urine and neutrophil CD64 expression was highly elevated.
      Despite undergoing intensive treatment, the patient developed sepsis and died 12
      days after admission. An autopsy indicated that while the Legionella infection
      had almost been controlled, a subarachnoid hemorrhage was the ultimate cause of
      death. 

PMID- 25948364
TI  - Sparganosis presenting as pericardial effusion and lung lesions.
AB  - We herein report a rare form of sparganosis in a 29-year-old man presenting with
      pericardial effusion and lung lesions. The diagnosis was confirmed by the
      patient's history of eating inadequately cooked snake, significant elevated
      eosinophils in the peripheral blood and pericardial effusion, and marked positive
      reactions against Sparganum mansoni antigen in the serum. After two consecutive
      doses of praziquantel treatment, the patient's symptoms and laboratory and
      imaging findings were improved. Both specific antibody detection and follow-up of
      the patient's eosinophils, serum antibody, and imaging changes are important for
      sparganosis diagnosis, particularly in cases without a subcutaneous lump or mass.

PMID- 25948363
TI  - Acute kidney injury due to renal sarcoidosis during etanercept therapy: a case
      report and literature review.
AB  - We herein report a case of renal sarcoidosis presenting as acute kidney injury
      (AKI) during treatment with etanercept for rheumatoid arthritis. Blood tests
      showed a high level of angiotensin-converting enzyme and a renal biopsy
      demonstrated non-caseating granulomatous tubulointerstitial nephritis. The
      administration of high-dose steroid therapy (1 mg/kg) and discontinuation of
      etanercept resulted in an improvement in the patient's renal function. Although
      renal sarcoidosis induced by anti-tumor necrosis factor (TNF) therapy is an
      extremely rare manifestation, this case suggests that renal sarcoidosis should be
      considered in the differential diagnosis of AKI in patients receiving anti-TNF
      therapy, as providing an early diagnosis and treatment is important for
      preventing irreversible renal impairment. 

PMID- 25948365
TI  - A rare case report of central line-associated bloodstream infection caused by
      Cryptococcus arboriformis.
AB  - Cryptococcus arboriformis (C. arboriformis) is a novel Cryptococcus species
      belonging to the genus Trichosporonales. This novel species was identified
      definitively in 2007 using D1/D2 26S ribosomal DNA gene sequencing. In this
      article, we present a rare case of central line-associated bloodstream infection
      caused by C. arboriformis with successful treatment of this infection. 

PMID- 25948366
TI  - A rare but potentially lethal case of tuberculous aortic aneurysm presenting with
      repeated attacks of abdominal pain.
AB  - Tuberculous aortic aneurysm is an extremely rare disease with a high mortality
      rate. The clinical features of this condition are highly variable, ranging from
      asymptomatic with or without constitutional symptoms, abdominal pain to frank
      rupture, bleeding and shock. We herein report the case of a 56-year-old man with
      a large tuberculous mycotic aneurysm in the abdominal aorta with an initial
      presentation of repeated attacks of abdominal pain lasting for several months.
      Due to the vague nature of the initial symptoms, tuberculous aortic aneurysms may
      take several months to diagnose. This case highlights the importance of having a
      high index of suspicion and providing timely surgery for this rare but
      potentially lethal disease. 

PMID- 25948368
TI  - Tumor-like lesion of a hepatoduodenal ligament due to tuberculosis.

PMID- 25948367
TI  - Severe ovarian hyperstimulation syndrome complicated by Stenotrophomonas
      maltophilia peritonitis: a case report and literature review.
AB  - Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic disorder resulting from
      ovulation induction. Although the occurrence of this disorder is rare, it can be
      potentially life-threatening in its most severe forms. We herein present the case
      of a young nulliparous woman who presented with features of abdominal compartment
      syndrome and was subsequently diagnosed with severe OHSS. All physicians, in
      particular critical care doctors, must be aware of this rare, but potentially
      life-threatening iatrogenic disorder. 

PMID- 25948369
TI  - Arrhythmogenic isthmus bounded with post-surgical right ventricular aneurysm.

PMID- 25948370
TI  - Rare abdominal aortic aneurysm in Marfan's pathology.

PMID- 25948371
TI  - Timing of sputum cultivation in cases of pulmonary mucormycosis.

PMID- 25948372
TI  - Complete colonic compression by an overfilled urinary bladder.

PMID- 25948373
TI  - Clinical usefulness of procalcitonin as a marker of sepsis: a novel predictor of
      causative pathogens?

PMID- 25948374
TI  - Clinical usefulness of procalcitonin as a marker of sepsis: a novel predictor of
      causative pathogens? The authors reply.

PMID- 25948375
TI  - Ferrocene/fullerene hybrids showing large second-order nonlinear optical
      activities: impact of the cage unit size.
AB  - The electron donor-acceptor complexes, which undergo intramolecular charge
      transfer under external stimulus, are an emerging class of materials showing
      important application in nonlinear optics. Synthesizing ferrocene/fullerene
      complexes through face-to-face fusion would enjoy the merits of both ferrocene
      and fullerene due to their strong donor-acceptor interactions. Four
      ferrocene/fullerene hybrid complexes with the gradual extension of fullerene cage
      size, including CpFe(C60H5), CpFe(C66H5), CpFe(C70H5), and CpFe(C80H5) (Cp is
      cyclopentadienyl), have been investigated by density functional theory. These
      hybrid molecules give eclipsed and staggered isomers. The main reason that the
      eclipsed isomer is stable is that the eclipsed structure possesses large
      CpFefullerene bonding energy. The CpFefullerene interaction is smaller than that
      of CpFefullerene, which must come from two different interfaces. The presence of
      covalent bond character between CpFe and fullerene is supported by the localized
      orbital locator, deformation of electron density distribution and energy
      decomposition analysis. Significantly, the absorption bands and first
      hyperpolarizabilities of these hybrid complexes are strongly sensitive to the
      fullerene cage size, which is ascribed to a change in the charge transfer
      pattern, especially for CpFe(C80H5), which displays reverse pi -> pi* charge
      transfer from bottom to top cage, leading to notable hyperpolarizability.
      Investigation of the structure-property relationship at the molecular level can
      benefit the design and preparation of such hybrid complexes in chemistry and
      materials science. 

PMID- 25948376
TI  - Nanomedicine as an emerging platform for metastatic lung cancer therapy.
AB  - Metastatic lung cancer is one of the most common cancers leading to mortality
      worldwide. Current treatment includes chemo- and pathway-dependent therapy aiming
      at blocking the spread and proliferation of these metastatic lesions.
      Nanomedicine is an emerging multidisciplinary field that offers unprecedented
      access to living cells and promises the state of the art in cancer detection and
      treatment. Development of nanomedicines as drug carriers (nanocarriers) that
      target cancer for therapy draws upon principles in the fields of chemistry,
      medicine, physics, biology, and engineering. Given the zealous activity in the
      field as demonstrated by more than 30 nanocarriers already approved for clinical
      use and given the promise of recent clinical results in various studies,
      nanocarrier-based strategies are anticipated to soon have a profound impact on
      cancer medicine and human health. Herein, we will detail the latest innovations
      in therapeutic nanomedicine with examples from lipid-based nanoparticles and
      polymer-based approaches, which are engineered to deliver anticancer drugs to
      metastatic lung cells. Emphasis will be placed on the latest and most attractive
      delivery platforms, which are developed specifically to target lung metastatic
      tumors. These novel nanomedicines may open new avenues for therapeutic
      intervention carrying new class of drugs such as RNAi and mRNA and the ability to
      edit the genome using the CRISPER/Cas9 system. Ultimately, these strategies might
      become a new therapeutic modality for advanced-stage lung cancer. 

PMID- 25948377
TI  - Radiation therapy for oligometastatic non-small cell lung cancer.
AB  - Interest has been increasing in the treatment of non-small cell lung cancer
      (NSCLC) patients with limited or oligometastatic disease. Surgery has
      historically been used to remove non-small cell lung cancer metastases, but
      recent developments including advanced radiotherapy planning and delivery
      techniques, often called stereotactic body radiotherapy (SBRT) or stereotactic
      ablative radiotherapy (SABR), has been associated with high rates of treated
      metastasis control. Therefore, given common comorbid disease, often precluding
      surgery, an increasing number of oligometastatic NSCLC patients are receiving
      radiation for ablation of all disease. Early results have reported favorable
      survival for some, with improved median survival, and approximately 25 % alive
      long term. Patients with fewer metastases, those treated to all known cancerous
      sites, and longer disease-free intervals tend to have better outcomes. While
      promising, better clinical criteria are needed to optimize patient selection. The
      biologic underpinnings of the oligometastatic state are beginning to be
      demonstrated with specific microRNAs being associated with limited or no
      progression both in human samples and murine models. Clinical trials are ongoing
      to improve the techniques used to deliver radiotherapy for NSCLC oligometastases.
      Ideally, randomized studies will need to be conducted to demonstrate the utility
      of these treatments suggested by the uncontrolled studies to date. In lieu of
      these, data presented here may help guide clinicians as to appropriate patient
      selection. 

PMID- 25948378
TI  - A patient with polymerase E1 deficiency (POLE1): clinical features and overlap
      with DNA breakage/instability syndromes.
AB  - BACKGROUND: Chromosome instability syndromes are a group of inherited conditions
      associated with chromosomal instability and breakage, often leading to
      immunodeficiency, growth retardation and increased risk of malignancy. CASE
      PRESENTATION: We performed exome sequencing on a girl with a suspected chromosome
      instability syndrome that manifested as growth retardation, microcephaly,
      developmental delay, dysmorphic features, poikiloderma, immune deficiency with
      pancytopenia, and myelodysplasia. She was homozygous for a previously reported
      splice variant, c.4444 + 3A > G in the POLE1 gene, which encodes the catalytic
      subunit of DNA polymerase E. CONCLUSION: This is the second family with POLE1
      deficency, with the affected individual demonstrating a more severe phenotype
      than previously described.

PMID- 25948380
TI  - Use of alum water treatment sludge to stabilize C and immobilize P and metals in
      composts.
AB  - Alum water treatment sludge is composed of amorphous hydroxyl-Al, which has
      variable charge surfaces with a large Brunauer-Emmett-Teller (BET) surface area
      (103 m(-2) g(-1)) capable of specific adsorption of organic matter molecules,
      phosphate, and heavy metals. The effects of adding dried, ground, alum water
      treatment sludge (10% w/w) to the feedstock for composting municipal green waste
      alone, green waste plus poultry manure, or green waste plus biosolids were
      determined. Addition of water treatment sludge reduced water soluble C, microbial
      biomass C, CO2 evolution, extractable P, and extractable heavy metals during
      composting. The decrease in CO2 evolution (i.e., C sequestration) was greatest
      for poultry manure and least for biosolid composts. The effects of addition of
      water treatment sludge to mature green waste-based poultry manure and biosolid
      composts were also determined in a 24-week incubation experiment. The composts
      were either incubated alone or after addition to a soil. Extractable P and heavy
      metal concentrations were decreased by additions of water treatment sludge in all
      treatments, and CO2 evolution was also reduced from the poultry manure compost
      over the first 16-18 weeks. However, for biosolid compost, addition of water
      treatment sludge increased microbial biomass C and CO2 evolution rate over the
      entire 24-week incubation period. This was attributed to the greatly reduced
      extractable heavy metal concentrations (As, Cr, Cu, Pb, and Zn) present following
      addition of water treatment sludge, and thus increased microbial activity. It was
      concluded that addition of water treatment sludge reduces concentrations of
      extractable P and heavy metals in composts and that its effect on organic matter
      stabilization is much greater during the composting process than for mature
      compost because levels of easily decomposable organic matter are initially much
      higher in the feedstock than those in matured composts.

PMID- 25948379
TI  - Investigations on sediment toxicity of German rivers applying a standardized
      bioassay battery.
AB  - River sediments may contain a huge variety of environmental contaminants and play
      a key role in the ecological status of aquatic ecosystems. Contaminants adsorbed
      to sediments and suspended solids may contribute directly or after remobilization
      to an adverse ecological and chemical status of surface water. In this subproject
      of the joint research project DanTox, acetonic Soxhlet extracts from three German
      river sediments from the River Rhine (Altrip and Ehrenbreitstein with moderate
      contamination) and River Elbe (Veringkanal Hamburg heavily contaminated) were
      prepared and redissolved in dimethyl sulfoxide (DMSO). These extracts were
      analyzed with a standard bioassay battery with organisms from different trophic
      levels (bacteria, algae, Daphnia, fish) as well as in the Ames test and the umuC
      test for bacterial mutagenicity and genotoxicity according to the respective OECD
      and ISO guidelines. In total, 0.01% (standard) up to 0.25% (only fish embryo
      test) of the DMSO sediment extract was dosed to the test systems resulting in
      maximum sediment equivalent concentrations (SEQ) of 2 up to 50 g l(-1). The
      sediment of Veringkanal near Hamburg harbor was significantly more toxic in most
      tests compared to the sediment extracts from Altrip and Ehrenbreitstein from the
      River Rhine. The most toxic effect found for Veringkanal was in the algae test
      with an ErC50 (72 h) of 0.00226 g l(-1) SEQ. Ehrenbreitstein and Altrip samples
      were about factor 1,000 less toxic. In the Daphnia, Lemna, and acute fish
      toxicity tests, no toxicity at all was found at 2 g l(-1) SEQ. corresponding to
      0.01% DMSO. Only when increasing the DMSO concentration the fish embryo test
      showed a 22-fold higher toxicity for Veringkanal than for Ehrenbreitstein and
      Altrip samples, while the toxicity difference was less evident for the Daphnia
      test due to the overlaying solvent toxicity above 0.05% dimethyl sulfoxide
      (DMSO). The higher toxicities observed with the Veringkanal sample are supported
      by the PAH and PCB concentrations analyzed in the sediments. The sediment
      extracts of Altrip and Veringkanal were mutagenic in the Ames tester strain TA98
      with metabolic activation (S9-mix). The findings allow a better ecotoxicological
      characterization of the sediments extensively analyzed in all subprojects of the
      DanTox project (e.g., Garcia-Kaeufer et al. Environ Sci Pollut Res. doi:
      10.1007/s11356-014-3894-4 , 2014; Schiwy et al. Environ Sci Pollut Res. doi:
      10.1007/s11356-014-3185-0 , 2014; Hollert and Keiter 2015). In the absence of
      agreed limit values for sediment extracts in standard tests, further data with
      unpolluted reference sediments are required for a quantitative risk assessment of
      the investigated polluted sediments.

PMID- 25948381
TI  - Variability of cadmium, lead, and zinc tolerance and accumulation among and
      between germplasms of the fiber crop Boehmeria nivea with different root-types.
AB  - Crop germplasms substantially vary in their tolerance for and accumulation of
      heavy metals, and assessment of this variability plays a significant role in
      selecting species to use in phytoremediation projects. Here, we examined
      germplasm-variations in cadmium (Cd), lead (Pb), and zinc (Zn) tolerance and
      accumulation in ramie (Boehmeria nivea), a fiber crop native to China, which has
      received little attention. In an 8-week greenhouse test, fourteen germplasms of
      ramie, among and within deep, middle, and shallow rooted-types, were compared for
      growth and metal accumulation traits. Results showed that both tolerance and
      accumulation traits varied across germplasms and rooted-types. The deep rooted
      type germplasms produced more biomass and had higher tolerance to metals than the
      two others. In addition, considerable variations in metal accumulation were
      observed among plant organs (root, stem, and leaf), rooted-types, germplasms, and
      metal supply. However, the observed variations in metal tolerance and
      accumulation among both germplasms and rooted-types were not significant in most
      cases. In addition to supporting the idea of a certain degree of constitutional
      metal tolerance for ramie, our results also contribute to deep-rooted germplasms
      of ramie as a good candidate, rather than middle-/shallow- ones as a least-bad
      option, for the remediation of multi metal-contaminated soils. 

PMID- 25948382
TI  - Short-term exposure to low doses of rotenone induces developmental, biochemical,
      behavioral, and histological changes in fish.
AB  - Rotenone, a natural compound derived from plants of the genera Derris and
      Lonchocarpus, is used worldwide as a pesticide and piscicide. This study aims to
      assess short-term toxicity of rotenone to early-life stages of the fish Danio
      rerio and Poecilia reticulata using a wide and integrative range of biomarkers
      (developmental, biochemical, behavioral, and histopathological). Moreover, the
      species sensitivity distribution (SSD) approach was used to compare rotenone
      acute toxicity to fish species. Toxicity tests were based on the OECD protocols,
      fish embryo toxicity test (for D. rerio embryos), and fish acute toxicity test
      (for P. reticulata juveniles). D. rerio embryos were used to estimate lethal
      concentrations and analyze embryonic and enzymatic alterations (activity of
      catalase, glutathione-S-transferase, and cholinesterase), while P. reticulata
      juveniles were used for the assessment of histological damage in the gills and
      liver. Rotenone induced significant mortality in zebrafish embryos with a 96-h
      lethal concentration 50% (LC50) = 12.2 MUg/L. Rotenone was embryotoxic, affecting
      the development of D. rerio embryos, which showed cardiac edema; tail
      deformities; loss of equilibrium; and a general delay characterized by lack of
      tail detachment, delayed somite formation, yolk sac absorption, and lack of
      pigmentation. Biochemical biomarker inhibition was observed for concentrations
      >=1 MUg/L for CAT and glutathione-S-transferase (GST) and for cholinesterase
      (ChE) in concentration from 10 MUg/L. Behavioral changes were observed for P.
      reticulata juveniles exposed to concentrations equal to or above 25 MUg/L of
      rotenone; moreover, histological damage in the liver and gills of fish exposed to
      concentrations equal to or above 2.5 MUg/L could be observed. A hazard
      concentration 5% (HC5) of 3.2 MUg/L was estimated considering the acute toxicity
      data for different fish species (n = 49). Lethal and sublethal effects of
      rotenone raise a concern about its effects on nontarget fish species, especially
      because rotenone and its metabolite rotenolone are frequently reported in the
      microgram range in natural environments for several days after field
      applications. Rotenone should be used with caution. Given the high toxicity and
      wide range of sublethal effects here reported, further studies in a chronic
      exposure scenario are recommended.

PMID- 25948383
TI  - Factors influencing the heavy metal bioaccessibility in soils were site dependent
      from different geographical locations.
AB  - A soil survey was conducted in urban areas from five sites, including Beijing,
      Baotou, Datong, Fuyang, and Xiantao in China. The objective was to explore the
      most significant factors that may impact the bioaccessibility of heavy metals
      (Bio-HMs), including As, Cr, Cu, Pb, and Zn, in soils. Twenty to 30 composite
      soil samples were collected at each site. The various soil properties, including
      pH, particle size, Fe/Mn, and organic matter contents, were analyzed. The
      chemical operated forms of HMs in soils were measured by the Bureau of Reference
      (BCR) sequential extraction scheme, while the Bio-HMs were determined by the
      simple bioaccessibility extraction test (SBET) procedure. The concentrations of
      total heavy metals (T-HMs) in soils from different sites (cities) were in the
      range as As (5.69-9.86), Cr (77.42-230.20), Cu (15.68-36.54), Pb (14.12-58.93),
      and Zn (38.66-183.46) mg/kg. Cu and Pb had higher relative bioaccessibilities (48
      70%) than those of As and Cr (6-15%), indicating higher health risks of the
      former than the latter two HMs. The Bio-HMs for various HMs were comparable to
      the first two or three combined BCR extracted fractions, with an exception of Cu,
      whose Bio-HMs were larger than the combined three BCR fractions, indicating that
      Cu was highly accessible in soils as compared with other HMs. Factor analysis
      showed that all variables, including soil property parameters and BCR extracted
      fractions, could be represented by three common factors extracted with higher
      than 0.5 loadings and ~80% cumulative contribution to the total variance. Among
      the three common factors, factor 1, containing mainly pH, texture, and Fe/Mn
      variables, and factor 3, containing mainly organic matter variable, could be
      attributed to geographical regions, while factor 2, containing mainly BCR
      extracted fractions, could be ascribed to relative bioaccessibility of HMs (R-Bio
      HMs). Interactive mapping of the main factors and cluster analysis were
      consistent, which supported the "site gathering" of the soil sample pools,
      suggesting that the Bio-HMs in soils in different geographical localities were
      site dependent.

PMID- 25948384
TI  - Environmental fate of the herbicide MCPA in agricultural soils amended with fresh
      and aged de-oiled two-phase olive mill waste.
AB  - Olive oil agrifood industry generates large amounts of waste whose recycling as
      organic amendment represents an alternative to their disposal. The impact of de
      oiled two-phase olive mill waste (DW) on the fate of 4-chloro-2
      methylphenoxyacetic acid (MCPA) in Mediterranean agricultural soils was
      evaluated. Furthermore, the effect of the transformation of organic matter from
      this waste under field conditions was assessed. Four Mediterranean agricultural
      soils were selected and amended in laboratory with fresh DW and field-aged DW (DW
      and ADW treatments, respectively). Adsorption capacity increased by factors
      between 1.18 and 3.59, for the DW-amended soils, and by factor of 4.93, for ADW
      amended soil, with respect to unamended soils, when 5% amendment was applied. The
      DW amendment had inhibitory effect on dehydrogenase activity and slowed herbicide
      dissipation, whereas the opposite effect was observed in ADW treatments. In the
      field-amended soil, the amount of MCPA leached was significantly reduced from
      56.9% for unamended soil to 15.9% at the 5% rate. However, leaching losses of
      MCPA increased in the laboratory-amended soils, because of their high water
      soluble organic carbon values which could enhance MCPA mobility, especially in
      the acidic soils. Therefore, the application of DW as organic amendment in
      Mediterranean agricultural soils could be an important management strategy to
      reduce MCPA leaching, especially if the organic matter had been previously
      transformed by ageing processes.

PMID- 25948387
TI  - MoCl5 as an effective chlorinating agent towards alpha-amino acids: synthesis of
      alpha-ammonium-acylchloride salts and alpha-amino-acylchloride complexes.
AB  - The reactivity of MoCl5 with alpha-amino acids was investigated for the first
      time by choosing CH2Cl2 as the reaction medium. The interaction of MoCl5 with l
      proline proceeded with Cl/O interchange and led to the formation of
      [NH2(CH2)3CHC(O)Cl][MoOCl4], 1, in 63% yield. The reactions of MoCl5 with l
      phenylalanine, sarcosine, N,N-dimethylglycine and N,N-dimethyl-l-phenylalanine
      afforded the alpha-amino-acylchloride complexes MoOCl3[O[double bond, length as m
      dash]C(Cl)CH(R)N(R')(R'')] (R = CH2Ph, R' = R'' = H, 2a; R = R' = H, R'' = Me,
      2b; R = H, R' = R'' = Me, 2c R = CH2Ph, R' = R'' = Me, 2d), in ca. 70% yields.
      According to DFT studies, 2a,d are mononuclear Mo(v) octahedral complexes bearing
      a N,O-coordinated alpha-amino-acylchloride ligand. The presumed species formed
      during the first stages of the MoCl5/l-phenylalanine interaction were DFT
      elucidated, thus the calculated Gibbs free energy profile for the multi-step
      reaction of MoCl5 with l-phenylalanine was traced. [NH3CH(CH2Ph)C(O)Cl][MoOCl4],
      3, acting as an intermediate in the course of the formation of 2a, was isolated
      by combination of [NH3CH(CH2Ph)C(O)Cl][Cl] with MoOCl3.

PMID- 25948385
TI  - Fish consumption recommendations to conform to current advice in regard to
      mercury intake.
AB  - This article reviews fish consumption data, mercury tolerable intake values, and
      mercury (Hg) content in fish, based on several reports from the Food and
      Agriculture Organization and European Union. The study assumptions are valid
      based on the current established USEPA reference dose (RfD). Combining the number
      of meals (per week), amount of fish ingested (by meal), and levels of MeHg in
      fish, this study calculates and presents isocurves indicating the maximum number
      of fishmeal per week without exceeding the USEPA RfD for methylmercury (MeHg).
      RfD are assumed to be the "exposure dose that is likely to be without deleterious
      effect even if continued exposure occurs over a lifetime." The study points out
      that even considering a single 50-g fish meal per week, the USEPA RfD would be
      exceeded, triggered by values above 0.84 MUg g(-1) of MeHg in fish, and this
      despite being allowed levels up to 1.0 MUg g(-1) of MeHg in fish consumption!
      Have we a health risk? Fish consumption is expected to be relatively stable,
      while anthropogenic mercury emissions are expected to stabilize or even to
      increase beyond current values. How many meals of fish per week can we have,
      combining the number of fish meals per week, amount of fish ingested by meal, and
      levels of MeHg in fish? 

PMID- 25948388
TI  - Room temperature stable zinc carbonyl complex formed in zeolite ZSM-5 and its
      hydrogenation reactivity: a solid-state NMR study.
AB  - The structure and reactivity of a room temperature stable zinc carbonyl complex
      in Zn-modified H-ZSM-5 zeolite were revealed by solid-state NMR spectroscopy. 

PMID- 25948386
TI  - Prevalence of antibiotic resistance genes of wastewater and surface water in
      livestock farms of Jiangsu Province, China.
AB  - The overuse of antibiotics in livestock farms is general, leading to a wide
      distribution of antibiotic resistance genes (ARGs) in aquatic environment
      adjacent to livestock farms. However, researches of the distribution and types of
      ARGs in aquatic environment of China are still in the initial stage. In this
      study, wastewater and surface water samples were collected from 12 livestock
      farms (four pig farms, four cattle farms, and four chicken farms) in Jiangsu
      Province of China. The prevalence, abundance, and distribution of 22 ARGs were
      investigated, which were categorized into six groups, including nine tetracyclin
      resistance genes, three sulfonamides resistance genes, three quinolone resistance
      genes, two macrolide resistance genes, three aminoglycoside resistance genes, and
      two multidrug resistance genes, employing quantitative real-time PCR (qPCR). The
      results suggested that all of the 22 ARGs were detected in samples. Sul1, sul2,
      and tetM were the most abundant with the average concentration of 3.84 * 10(1)
      copies/16S recombinant RNA (rRNA) gene copies, 1.62 * 10(1) copies/16S rRNA gene
      copies, 2.33 * 10(1) copies/16S rRNA gene copies, respectively. Principle
      component analysis revealed that the comprehensive pollution of ARGs in northern
      Jiangsu was more serious. ARGs in wastewater were more abundant when compared to
      that in surface water. A preliminary study regarding the fate of ARGs after an
      aerobiotic process showed that tetA, tetC, sul1, sul2, oqxB, and qnrS were
      significantly increased. And, among the tetracycline resistance genes, the efflux
      pump genes were enriched while the ribosomal protection protein encoding genes
      were decreased in the aerobiotic process. The prevalance of ARGs in water
      environment is of concern; more surveillance is required to determine the
      pollution level and pattern of antibiotic resistance genes. 

PMID- 25948389
TI  - Fabrication of periodic arrays of metallic nanoparticles by block copolymer
      templates on HfO2 substrates.
AB  - Block copolymer-based templates can be exploited for the fabrication of ordered
      arrays of metal nanoparticles (NPs) with a diameter down to a few nanometers. In
      order to develop this technique on metal oxide substrates, we studied the self
      assembly of polymeric templates directly on the HfO2 surface. Using a random
      copolymer neutralization layer, we obtained an effective HfO2 surface
      neutralization, while the effects of surface cleaning and annealing temperature
      were carefully examined. Varying the block copolymer molecular weight, we
      produced regular nanoporous templates with feature size variable between 10 and
      30 nm and a density up to 1.5 * 1011 cm-2. With the adoption of a pattern
      transfer process, we produced ordered arrays of Pt and Pt/Ti NPs with diameters
      of 12, 21 and 29 nm and a constant size dispersion (sigma) of 2.5 nm. For the
      smallest template adopted, the NP diameter is significantly lower than the
      original template dimension. In this specific configuration, the granularity of
      the deposited film probably influences the pattern transfer process and very
      small NPs of 12 nm were achieved without a significant broadening of the size
      distribution.

PMID- 25948390
TI  - Charge order from orbital-dependent coupling evidenced by NbSe2.
AB  - Niobium diselenide has long served as a prototype of two-dimensional charge
      ordering, believed to arise from an instability of the electronic structure
      analogous to the one-dimensional Peierls mechanism. Despite this, various
      anomalous properties have recently been identified experimentally, which cannot
      be explained by Peierls-like weak-coupling theories. Here, we consider instead a
      model with strong electron-phonon coupling, taking into account both the full
      momentum and orbital dependence of the coupling matrix elements. We show that
      both are necessary for a consistent description of the full range of experimental
      observations. We argue that NbSe2 is typical in this sense, and that any charge
      ordered material in more than one dimension will generically be shaped by the
      momentum and orbital dependence of its electron-phonon coupling as well as its
      electronic structure. The consequences will be observable in many charge-ordered
      materials, including cuprate superconductors. 

PMID- 25948392
TI  - The response of Omega-loop D dynamics to truncation of trimethyllysine 72 of
      yeast iso-1-cytochrome c depends on the nature of loop deformation.
AB  - Trimethyllysine 72 (tmK72) has been suggested to play a role in sterically
      constraining the heme crevice dynamics of yeast iso-1-cytochrome c mediated by
      the Omega-loop D cooperative substructure (residues 70-85). A tmK72A mutation
      causes a gain in peroxidase activity, a function of cytochrome c that is
      important early in apoptosis. More than one higher energy state is accessible for
      the Omega-loop D substructure via tier 0 dynamics. Two of these are alkaline
      conformers mediated by Lys73 and Lys79. In the current work, the effect of the
      tmK72A mutation on the thermodynamic and kinetic properties of wild-type iso-1
      cytochrome c (yWT versus WT*) and on variants carrying a K73H mutation (yWT/K73H
      versus WT*/K73H) is studied. Whereas the tmK72A mutation confers increased
      peroxidase activity in wild-type yeast iso-1-cytochrome c and increased dynamics
      for formation of a previously studied His79-heme alkaline conformer, the tmK72A
      mutation speeds return of the His73-heme alkaline conformer to the native state
      through destabilization of the His73-heme alkaline conformer relative to the
      native conformer. These opposing behaviors demonstrate that the response of the
      dynamics of a protein substructure to mutation depends on the nature of the
      perturbation to the substructure. For a protein substructure which mediates more
      than one function of a protein through multiple non-native structures, a mutation
      could change the partitioning between these functions. The current results
      suggest that the tier 0 dynamics of Omega-loop D that mediates peroxidase
      activity has similarities to the tier 0 dynamics required to form the His79-heme
      alkaline conformer. 

PMID- 25948394
TI  - The C-terminal extension of PrhG impairs its activation of hrp expression and
      virulence in Ralstonia solanacearum.

PMID- 25948393
TI  - Incorporation of molybdenum in rubredoxin: models for mononuclear molybdenum
      enzymes.
AB  - Molybdenum is found in the active site of enzymes usually coordinated by one or
      two pyranopterin molecules. Here, we mimic an enzyme with a mononuclear
      molybdenum-bis pyranopterin center by incorporating molybdenum in rubredoxin. In
      the molybdenum-substituted rubredoxin, the metal ion is coordinated by four
      sulfurs from conserved cysteine residues of the apo-rubredoxin and two other
      exogenous ligands, oxygen and thiol, forming a Mo((VI))-(S-Cys)4(O)(X) complex,
      where X represents -OH or -SR. The rubredoxin molybdenum center is stabilized in
      a Mo(VI) oxidation state, but can be reduced to Mo(IV) via Mo(V) by dithionite,
      being a suitable model for the spectroscopic properties of resting and reduced
      forms of molybdenum-bis pyranopterin-containing enzymes. Preliminary experiments
      indicate that the molybdenum site built in rubredoxin can promote oxo transfer
      reactions, as exemplified with the oxidation of arsenite to arsenate. 

PMID- 25948395
TI  - New insights into the oxidative dehydrogenation of propane on borate-modified
      nanodiamond.
AB  - For the first time, we give a fundamental understanding of the effect of borate
      modified nanodiamond on propane oxidative dehydrogenation reaction. Upon
      increasing the loading amount of borate on the carbon surface, the propene
      selectivity shows a volcanic curve. The adsorption sites of borate at different
      loading amounts are thoroughly considered. 

PMID- 25948397
TI  - [Comorbid diseases of dementia].

PMID- 25948398
TI  - Maggot excretion products from the blowfly Lucilia sericata contain contact
      phase/intrinsic pathway-like proteases with procoagulant functions.
AB  - For centuries, maggots have been used for the treatment of wounds by a variety of
      ancient cultures, as part of their traditional medicine. With increasing
      appearance of antimicrobial resistance and in association with diabetic ulcers,
      maggot therapy was revisited in the 1980s. Three mechanisms by which sterile
      maggots of the green bottle fly Lucilia sericata may improve healing of chronic
      wounds have been proposed: Biosurgical debridement, disinfecting properties, and
      stimulation of the wound healing process. However, the influence of maggot
      excretion products (MEP) on blood coagulation as part of the wound healing
      process has not been studied in detail. Here, we demonstrate that specific MEP
      derived serine proteases from Lucilia sericata induce clotting of human plasma
      and whole blood, particularly by activating contact phase proteins factor XII and
      kininogen as well as factor IX, thereby providing kallikrein-bypassing and factor
      XIa-like activities, both in plasma and in isolated systems. In plasma samples
      deficient in contact phase proteins, MEP restored full clotting activity, whereas
      in plasma deficient in either factor VII, IX, X or II no effect was seen. The
      observed procoagulant/intrinsic pathway-like activity was mediated by (chymo-)
      trypsin-like proteases in total MEP, which were significantly blocked by C1
      esterase inhibitor or other contact phase-specific protease inhibitors. No
      significant influence of MEP on platelet activation or fibrinolysis was noted.
      Together, MEP provides contact phase bypassing procoagulant activity and thereby
      induces blood clotting in the context of wound healing. Further characterisation
      of the active serine protease(s) may offer new perspectives for biosurgical
      treatment of chronic wounds. 

PMID- 25948399
TI  - The prevention, detection and management of cancer treatment-induced
      cardiotoxicity: a meta-review.
AB  - BACKGROUND: The benefits associated with some cancer treatments do not come
      without risk. A serious side effect of some common cancer treatments is
      cardiotoxicity. Increased recognition of the public health implications of cancer
      treatment-induced cardiotoxicity has resulted in a proliferation of systematic
      reviews in this field to guide practice. Quality appraisal of these reviews is
      likely to limit the influence of biased conclusions from systematic reviews that
      have used poor methodology related to clinical decision-making. The aim of this
      meta-review is to appraise and synthesise evidence from only high quality
      systematic reviews focused on the prevention, detection or management of cancer
      treatment-induced cardiotoxicity. METHODS: Using Cochrane methodology, we
      searched databases, citations and hand-searched bibliographies. Two reviewers
      independently appraised reviews and extracted findings. A total of 18 high
      quality systematic reviews were subsequently analysed, 67 % (n = 12) of these
      comprised meta-analyses. RESULTS: One systematic review concluded that there is
      insufficient evidence regarding the utility of cardiac biomarkers for the
      detection of cardiotoxicity. The following strategies might reduce the risk of
      cardiotoxicity: 1) The concomitant administration of dexrazoxane with
      anthracylines; 2) The avoidance of anthracyclines where possible; 3) The
      continuous administration of anthracyclines (>6 h) rather than bolus dosing; and
      4) The administration of anthracycline derivatives such as epirubicin or
      liposomal-encapsulated doxorubicin instead of doxorubicin. In terms of
      management, one review focused on medical interventions for treating
      anthracycline-induced cardiotoxicity during or after treatment of childhood
      cancer. Neither intervention (enalapril and phosphocreatine) was associated with
      statistically significant improvement in ejection fraction or mortality.
      CONCLUSION: This review highlights the lack of high level evidence to guide
      clinical decision-making with respect to the detection and management of cancer
      treatment-associated cardiotoxicity. There is more evidence with respect to the
      prevention of this adverse effect of cancer treatment. This evidence, however,
      only applies to anthracycline-based chemotherapy in a predominantly adult
      population. There is no high-level evidence to guide clinical decision-making
      regarding the prevention, detection or management of radiation-induced
      cardiotoxicity.

PMID- 25948400
TI  - Silymarin and lycopene administration in periparturient dairy cows: effects on
      milk production and oxidative status.
AB  - AIMS: To establish during late gestation and early lactation the effects of
      supplementing silymarin, a natural hepatoprotective substance, combined with a
      powerful antioxidant, lycopene, on milk production and on serum biomarkers of
      oxidative status. METHODS: Italian Friesian dairy cows were given individually a
      supplement containing a mixture of silymarin (7.77 g/day/cow) and lycopene (1.27
      g/day/cow) (n=10) or no supplement (control; n=10). Treatment was administered
      from 7 days before the expected calving date to the first 14 days in milk. At 7
      days before the expected calving date, at calving, and 7 days postpartum, body
      condition score (BCS) and concentrations in serum of reactive oxygen metabolites
      (ROM), total antioxidant capacity (OXY) and thiobarbituric acid reactive
      substances (TBARS) were evaluated. Bodyweight, milk production, and somatic cell
      count (SCC) were determined at 7, 14 and 21 days postpartum. RESULTS: The mean
      time of treatment prior to calving was 6.3 (min 4, max 11) days. Compared with
      control cows, treatment increased energy corrected milk yield (33.3 vs. 37.8 (SEM
      1.10) kg/day; p=0.006) and milk fat yield (1.14 vs. 1.32 (SEM 0.06) kg/day;
      p=0.05) over the first 21 days of lactation. Treated cows had lower mean log10
      SCC compared to control cows (4.9 vs. 5.24 (SEM 0.11) log10 cells/mL) and had
      lower overall concentration of TBARS (1.47 vs. 1.59 (SEM 0.016) nM/mL; p<0.001),
      but similar concentrations of ROM and OXY in serum. However there was a treatment
      by time interaction (p=0.09) for OXY, and at calving mean OXY was higher in
      treated cows compared with pre-calving values (p<0.001). CONCLUSIONS: Despite the
      acknowledged limitation of the study, i.e. the small number of animals, our
      results suggest that silymarin and lycopene, as health-beneficial feed
      supplements, may help dairy cows in metabolic adaptation during the first stages
      of lactation. CLINICAL RELEVANCE: During the peripartum period dairy cows suffer
      moderate-to-severe fatty liver and from an overproduction of free radicals. The
      supplementation of a mixture of silymarin and lycopene during these stressful
      days may be useful to mitigate these metabolic disorders with beneficial effects
      on the subsequent lactation.

PMID- 25948401
TI  - Molecular tools to support metabolic and immune function research in the Guinea
      Fowl (Numida meleagris).
AB  - BACKGROUND: Guinea fowl (Numidia meleagris) production as an alternative source
      of meat and poultry has shown potential for economic viability. However, there
      has been little progress in characterizing the transcriptome of the guinea fowl.
      In this study RNA-sequencing and de novo transcriptome assembly of several Guinea
      fowl tissues (pancreas, hypothalamus, liver, bone marrow and bursa) which play
      key roles in regulating feed intake, satiety, and immune function was performed
      using Illumina's Hi-Seq 2000. RESULTS: 74 million sequences were generated and
      assembled into 96,492 contigs using the Trinity software suite. Over 39,000 of
      these transcripts were found to have in silico translated protein sequences that
      are homologous to chicken protein sequences. Gene ontology analysis uncovered 416
      transcripts with metabolic functions and 703 with immune function. CONCLUSION:
      The transcriptome information presented here will support the development of
      molecular approaches to improve production efficiency of the guinea fowl and
      other avian species.

PMID- 25948402
TI  - Correction. Does a GLP-1 receptor agonist change glucose tolerance in patients
      treated with antipsychotic medications? Design of a randomised, double-blinded,
      placebo-controlled clinical trial.

PMID- 25948403
TI  - Correction. Protocol of the Australasian Malignant Pleural Effusion (AMPLE)
      trial: a multicentre randomised study comparing indwelling pleural catheter
      versus talc pleurodesis.

PMID- 25948404
TI  - The possibility of lifestyle and biological risk markers to predict morbidity and
      mortality in a cohort of young men after 26 years follow-up.
AB  - OBJECTIVES: To study the association between lifestyle and biological risk
      markers measured at one occasion, morbidity and mortality from cardiovascular
      disease (CVD) and cancer, and morbidity from diabetes approximately 26 years
      later. DESIGN: A follow-up study of a cohort of men, 33-42 years old at baseline.
      SETTING: Primary healthcare centre in Sweden. PARTICIPANTS: All 757 men, living
      in the community of Habo in Sweden in 1985, and all 652 of these participating in
      a health examination in 1985-1987. INTERVENTIONS: Health profile and a health
      dialogue with a nurse. A doctor invited the high-risk group to further dialogue
      and examination. Intervention programmes were carried out in the primary
      healthcare centre and in cooperation with local associations. MAIN OUTCOME
      MEASURES: CVD and cancer diagnoses from the Swedish National Board of Health and
      Welfare. Data from pharmacy registers of sold drugs concerning diabetes mellitus.
      RESULTS: The participants were divided in three groups based on summarised risk
      points from lifestyle (smoking, physical activity, alcohol consumption) and
      biological risk markers (body mass index (BMI), blood pressure, serum
      cholesterol) selected from the health profile. Comparisons were done between
      these groups. The group with the lowest summarised total risk points had a
      significantly lower risk for CVD and cancer compared with the group with the
      highest summarised risk points. The group with the lowest risk points concerning
      lifestyle had a significantly lower risk for CVD, and the group with lowest risk
      points for biological risk markers had a significantly lower risk for both CVD
      and cancer compared with the groups with the highest risk points. Smoking and
      serum cholesterol were the most important risk factors. In association to
      diabetes, BMI and smoking were the most important risk factors. CONCLUSIONS: Risk
      factors measured on one occasion seemed to be able to predict CVD, cancer and
      diabetes 26 years later.

PMID- 25948406
TI  - Correction. Protocol investigating the clinical utility of an objective measure
      of activity and attention (QbTest) on diagnostic and treatment decision-making in
      children and young people with ADHD - 'Assessing QbTest Utility in ADHD' (AQUA):
      a randomised controlled trial.

PMID- 25948405
TI  - Can variability in the effect of opioids on refractory breathlessness be
      explained by genetic factors?
AB  - OBJECTIVES: Opioids modulate the perception of breathlessness with a considerable
      variation in response, with poor correlation between the required opioid dose and
      symptom severity. The objective of this hypothesis-generating, secondary analysis
      was to identify candidate single nucleotide polymorphisms (SNP) from those
      associated with opioid receptors, signalling or pain modulation to identify any
      related to intensity of breathlessness while on opioids. This can help to inform
      prospective studies and potentially lead to better tailoring of opioid therapy
      for refractory breathlessness. SETTING: 17 hospice/palliative care services
      (tertiary services) in 11 European countries. PARTICIPANTS: 2294 people over 18
      years of age on regular opioids for pain related to cancer or its treatment.
      PRIMARY OUTCOME MEASURES: The relationship between morphine dose, breathlessness
      intensity (European Organisation for Research and Treatment of Cancer Core
      Quality of Life Questionnaire; EORTCQLQC30 question 8) and 112 candidate SNPs
      from 25 genes (n=588). SECONDARY OUTCOME MEASURES: The same measures for people
      on oxycodone (n=402) or fentanyl (n=429). RESULTS: SNPs not in Hardy-Weinberg
      equilibrium or with allele frequencies (<5%) were removed. Univariate
      associations between each SNP and breathlessness intensity were determined with
      Benjamini-Hochberg false discovery rate set at 20%. Multivariable ordinal
      logistic regression, clustering over country and adjusting for available
      confounders, was conducted with remaining SNPs. For univariate morphine
      associations, 1 variant on the 5-hydroxytryptamine type 3B (HTR3B) gene, and 4 on
      the beta-2-arrestin gene (ARRB2) were associated with more intense
      breathlessness. 1 SNP remained significant in the multivariable model: people
      with rs7103572 SNP (HTR3B gene; present in 8.4% of the population) were three
      times more likely to have more intense breathlessness (OR 2.86; 95% CIs 1.46 to
      5.62; p=0.002). No associations were seen with fentanyl nor with oxycodone.
      CONCLUSIONS: This large, exploratory study identified 1 biologically plausible
      SNP that warrants further study in the response of breathlessness to morphine
      therapy.

PMID- 25948408
TI  - Correction. Initial healthcare and coping preferences are associated with outcome
      1 year after whiplash trauma: a multicentre 1-year followup study.

PMID- 25948407
TI  - Genome-wide association study of perioperative myocardial infarction after
      coronary artery bypass surgery.
AB  - OBJECTIVES: Identification of patient subpopulations susceptible to develop
      myocardial infarction (MI) or, conversely, those displaying either intrinsic
      cardioprotective phenotypes or highly responsive to protective interventions
      remain high-priority knowledge gaps. We sought to identify novel common genetic
      variants associated with perioperative MI in patients undergoing coronary artery
      bypass grafting using genome-wide association methodology. SETTING: 107 secondary
      and tertiary cardiac surgery centres across the USA. PARTICIPANTS: We conducted a
      stage I genome-wide association study (GWAS) in 1433 ethnically diverse patients
      of both genders (112 cases/1321 controls) from the Genetics of Myocardial Adverse
      Outcomes and Graft Failure (GeneMAGIC) study, and a stage II analysis in an
      expanded population of 2055 patients (225 cases/1830 controls) combined from the
      GeneMAGIC and Duke Perioperative Genetics and Safety Outcomes (PEGASUS) studies.
      Patients undergoing primary non-emergent coronary bypass grafting were included.
      PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome variable was
      perioperative MI, defined as creatine kinase MB isoenzyme (CK-MB) values >=10*
      upper limit of normal during the first postoperative day, and not attributable to
      preoperative MI. Secondary outcomes included postoperative CK-MB as a
      quantitative trait, or a dichotomised phenotype based on extreme quartiles of the
      CK-MB distribution. RESULTS: Following quality control and adjustment for
      clinical covariates, we identified 521 single nucleotide polymorphisms in the
      stage I GWAS analysis. Among these, 8 common variants in 3 genes or intergenic
      regions met p<10(-5) in stage II. A secondary analysis using CK-MB as a
      quantitative trait (minimum p=1.26*10(-3) for rs609418), or a dichotomised
      phenotype based on extreme CK-MB values (minimum p=7.72*10(-6) for rs4834703)
      supported these findings. Pathway analysis revealed that genes harbouring top
      scoring variants cluster in pathways of biological relevance to extracellular
      matrix remodelling, endoplasmic reticulum-to-Golgi transport and inflammation.
      CONCLUSIONS: Using a two-stage GWAS and pathway analysis, we identified and
      prioritised several potential susceptibility loci for perioperative MI.

PMID- 25948409
TI  - Are two youth-focused interventions sufficient to empower youth with chronic
      health conditions in their transition to adult healthcare: a mixed-methods
      longitudinal prospective cohort study.
AB  - OBJECTIVES: To assess use, utility and impact of transition interventions
      designed to support and empower self-management in youth with chronic health
      conditions during transition into adult healthcare. DESIGN: A 4-year mixed-method
      prospective cohort study. SETTING: 2 academic paediatric hospitals (13 clinics)
      in Canada. PARTICIPANTS: 50 adolescents (42% male; mean age 17.9+/-0.9 years; 20
      underlying diagnoses) with transfer to adult care planned within 1 year.
      INTERVENTIONS: The Youth KIT (an organisational tool that includes goal setting
      activities); an online transition mentor. MAIN OUTCOME MEASURES: Frequency of
      use, utility and impact of the transition interventions; goal achievement; post
      transfer qualitative interviews with youth. RESULTS: 50 participants were
      enrolled during their last year of paediatric care; 36 (72%) were followed into
      adult care. All participants had access to the transition interventions from
      enrolment until the end of the study (exposure time: 12-47 months). Most youth
      (85%) reported using the medical/health section of the Youth KIT at least once;
      20 (40%) participants engaged in chats with the mentor. The overall perceived
      utility of both interventions was modest; the Youth KIT received the highest
      ratings for 'help with goal setting': (mean (SD): 4.2 (2.3)) on a 7-point Likert
      scale. 45 (90%) participants set 294 transition goals. Goal achievement
      performance and satisfaction increased over time (p<=0.001). The qualitative
      evidence revealed reasons behind the variability in use and utility of the
      interventions, the interconnectedness of life-course and healthcare transitions,
      and the need for stronger partnerships between paediatric and adult healthcare
      systems. CONCLUSIONS: Participants' perceptions about the utility of the Youth
      KIT and the online mentor were modest. Transition supports need to be carefully
      tailored, timed and integrated into healthcare systems. Individualised goal
      setting may be an important 'active ingredient' in optimising transition supports
      and outcomes. Interventions that focus on youth only are insufficient for
      empowering self-management.

PMID- 25948410
TI  - Interventions for migraine prophylaxis: protocol of an umbrella systematic review
      and network meta-analysis.
AB  - INTRODUCTION: Multiple interventions are effective for migraine prophylaxis.
      However, the comparative effectiveness of these interventions is still not clear.
      Therefore, the aim of this study is to summarise the direct and indirect evidence
      for pharmacological and non-pharmacological interventions to prevent migraine
      attack. METHODS AND ANALYSIS: We will perform an umbrella systematic review to
      identify eligible randomised controlled trials (RCTs) for the recommended
      interventions for migraine prophylaxis according to the guidelines. A
      comprehensive literature search will be conducted in MEDLINE, EMBASE and the
      Cochrane library for systematic reviews, which will be screened for RCTs. We will
      describe the general information of the RCTs for participants, interventions,
      outcome measurements, comparisons and the primary findings. Additionally, a
      network meta-analysis will be conducted to determine the comparative
      effectiveness of the treatments with a random-effects model. The absolute and
      relative effectiveness of the treatments will be provided. The heterogeneity and
      inconsistency between trials will be assessed by the I(2) statistical test and
      Cochrane's Q test. Risk of bias will be assessed and the overall strength of the
      evidence will be summarised. DISCUSSION: The result of this network meta-analysis
      will provide direct and indirect evidence of treatments for migraine prophylaxis,
      and it may provide a ranking of the treatments for patients and clinicians to
      help them select the best option. TRIAL REGISTRATION NUMBER: PROSPERO
      CRD42015015297.

PMID- 25948411
TI  - Impact of Physiological Symptoms and Complications of Colorectal Cancer on the
      Quality of Life of Patients at King Abdulaziz University Hospital.
AB  - Colorectal cancer (CRC) is common worldwide. The high prevalence of the disease
      raises concerns about how CRC influences the health-related quality of life
      (QoL). To explore the impact of physiological symptoms and complications of CRC
      on patients' QoL, we conducted a cross-sectional survey using the FACT-C self
      report instrument. The chi-square test was used to compare qualitative data. We
      found that pain was reported by most of the patients (n = 31; 77.5 %).
      Furthermore, male patients were more likely to complain of pain "mostly" as
      compared with females (P = .032). We found no significant differences between
      genders regarding general health-related questions. A greater proportion of male
      patients often complained of abdominal cramps (P = .542), weight loss (P = .086),
      and diarrhea (P = .408). More than half of the patients (n = 26; 65 %) reported
      having a good appetite; a greater proportion of males reported having a good
      appetite "mostly" (P = .014). Social and psychological qualities of life were not
      significantly different between male and female patients. Male and female
      patients did not differ in their report of disease acceptance (P = .420) and
      ability to enjoy life (P = .744). No difference was also found between genders
      regarding contentment with QoL (P = .793) or ability to sleep well (P = .695).
      Furthermore, there were no differences between genders regarding job fulfillment
      (P = .272). Our results add to the growing body of knowledge about the effect of
      CRC on QoL. Importantly, the differences in self-reported pain and appetite
      between male and female patients in our study suggest the importance of gender
      based treatments in improving patients' QoL.

PMID- 25948412
TI  - Using CBPR to Extend Prostate Cancer Education, Counseling, and Screening
      Opportunities to Urban-Dwelling African-Americans.
AB  - Community-based participatory research (CBPR) is becoming one of the dominant
      approaches for bringing evidence- and consensus-based cancer prevention and
      control practices to medically underserved communities. There are many examples
      of how CBPR has been useful for generating culturally specific solutions for
      different health issues that affect African-Americans. However, few examples
      exist in the literature on how the CBPR approach can be applied to address
      prostate cancer. This paper describes a collaborative process for linking inner
      city, African-American men to free prostate cancer education, physician
      counseling, and screening opportunities (prostate-specific antigen (PSA) testing
      and digital rectal examination (DRE)). The site of this community-based
      participatory project was the city of Buffalo, located in Erie County, New York.
      The collaborative, community-academic process that is described includes the
      following: (1) planning and conducting a community needs assessment to
      contextualize local prostate cancer issues, (2) organizing town and gown event
      planning, and (3) manipulating aspects of the built environment to build an
      infrastructure within the community to address disparities in screening
      opportunities. This paper concludes with a description of lessons learned that
      can help others develop and implement similar activities in other communities.

PMID- 25948413
TI  - Young Adult Cancer Survivors' Experience with Cancer Treatment and Follow-Up Care
      and Perceptions of Barriers to Engaging in Recommended Care.
AB  - We examined correlates of low engagement in the healthcare system, experiences
      with survivorship care, barriers to follow-up care, and potential resources for
      promoting follow-up care among young adult survivors of childhood cancers. We
      conducted a mixed-method study involving surveys of 106 survivors of childhood
      cancer aged 18-34 recruited from a university-affiliated children's hospital and
      an NCI-designated cancer center in the Southeastern USA. Phone-based
      semistructured interviews were then conducted in a subset of 26. Assessments
      included health factors, psychosocial factors, healthcare system interaction, and
      interest in resources to promote engagement in healthcare. Survey participants
      were on average 22.14 (SD = 3.16) years old, 50.0 % female, and 77.4 % White.
      Overall, 46.0 % had attended survivorship clinic, 47.2 % reported receiving a
      treatment summary, 68.9 % had a primary care provider, and 17.0 % reported no
      interaction with healthcare in the past 2 years. Correlates of less than annual
      healthcare provider visits included being older (p = 0.003), being male (p <
      0.001), lack of insurance (p = 0.002), and having had chemotherapy (p = 0.05).
      Participants reported varied experiences in terms of how health and treatment
      information was presented, from none or too little to overwhelming or anxiety
      provoking amounts. Barriers to engaging in survivorship care included no/limited
      insurance, time, or transportation; major life changes; anxiety; and difficulty
      transitioning from pediatrics to adult care. Participants highlighted the need
      for educational and psychosocial resources, particularly technology-based
      resources. Multilevel interventions are needed to increase engagement in
      survivorship care among young adult cancer survivors. Technology-based resources
      addressing social support and mental well-being are intervention possibilities.

PMID- 25948414
TI  - Superior Mechanical Properties of Epoxy Composites Reinforced by 3D
      Interconnected Graphene Skeleton.
AB  - Epoxy-based composites reinforced by three-dimensional graphene skeleton (3DGS)
      were fabricated in resin transfer molding method with respect to the difficulty
      in good dispersion and arrangement of graphene sheets in composites by directly
      mixing graphene and epoxy. 3DGS was synthesized in the process of self-assembly
      and reduction with poly(amidoamine) dendrimers. In the formation of 3DGS,
      graphene sheets were in good dispersion and ordered state, which resulted in
      exceptional mechanical properties and thermal stability for epoxy composites. For
      3DGS/epoxy composites, the tensile and compressive strengths significantly
      increased by 120.9% and 148.3%, respectively, as well as the glass transition
      temperature, which increased by a notable 19  degrees C, unlike the thermal
      exfoliation graphene/epoxy composites via direct-mixing route, which increased by
      only 0.20 wt % content of fillers. Relative to the graphene/epoxy composites in
      direct-mixing method mentioned in literature, the increase in tensile and
      compressive strengths of 3DGS/epoxy composites was at least twofold and
      sevenfold, respectively. It can be expected that 3DGS, which comes from
      preforming graphene sheets orderly and dispersedly, would replace graphene
      nanosheets in polymer nanocomposite reinforcement and endow composites with
      unique structure and some unexpected performance. 

PMID- 25948415
TI  - Electron Delocalization in Reduced Forms of 2-(BMes2)pyrene and 2,7
      Bis(BMes2)pyrene.
AB  - Reduction of 2-(BMes2)pyrene (B1) and 2,7-bis(BMes2)pyrene (B2) gives rise to
      anions with extensive delocalization over the pyrenylene bridge and between the
      boron centers at the 2- and 2,7-positions, the typically unconjugated sites in
      the pyrene framework. One-electron reduction of B2 gives a radical anion with a
      centrosymmetric semiquinoidal structure, while two-electron reduction produces a
      quinoidal singlet dianion with biradicaloid character and a relatively large S0
      T1 gap. These results have been confirmed by cyclic voltammetry, X-ray
      crystallography, DFT/CASSCF calculations, NMR, EPR, and UV-vis-NIR spectroscopy. 

PMID- 25948419
TI  - Manipulating interfacial hydrogens at palladium via STM.
AB  - In this contribution, we provide a detailed dynamical analysis of the interfacial
      hydrogen migration mediated by scanning tunneling microscopy (STM). Contributions
      from the STM-current and from the non-adiabatic couplings are taken into account
      using only first principle models. The slight asymmetry of the tunnelling rates
      with respect to the potential bias sign inferred from experimental observations
      is reproduced by weighting the contributions of the metal acceptor-donor states
      for the propagation of the impinging electrons. The quasi-thermal inelastic
      collision mechanism is treated perturbatively. The influence of hydrogen pre
      coverage is also investigated using new potential energy surfaces obtained from
      periodic density functional theory calculations. Fully quantum dynamical
      simulations of the system evolution are performed by solving the Pauli master
      equation, providing insight into the reaction mechanism of STM manipulation of
      subsurface hydrogens. It is observed that the hydrogen impurity favors
      resurfacing over occupation of the bulk and subsurface sites whenever possible.
      The present simulations give strong indication that the experimentally observed
      protuberances after STM-excitation are due to hydrogen accumulating in the
      vicinity of the surface. 

PMID- 25948416
TI  - Control of polarized assembly of actin filaments in cell motility.
AB  - Actin cytoskeleton remodeling, which drives changes in cell shape and motility,
      is orchestrated by a coordinated control of polarized assembly of actin
      filaments. Signal responsive, membrane-bound protein machineries initiate and
      regulate polarized growth of actin filaments by mediating transient links with
      their barbed ends, which elongate from polymerizable actin monomers. The barbed
      end of an actin filament thus stands out as a hotspot of regulation of filament
      assembly. It is the target of both soluble and membrane-bound agonists as well as
      antagonists of filament assembly. Here, we review the molecular mechanisms by
      which various regulators of actin dynamics bind, synergize or compete at filament
      barbed ends. Two proteins can compete for the barbed end via a mutually exclusive
      binding scheme. Alternatively, two regulators acting individually at barbed ends
      may be bound together transiently to terminal actin subunits at barbed ends,
      leading to the displacement of one by the other. The kinetics of these reactions
      is a key in understanding how filament length and membrane-filament linkage are
      controlled. It is also essential for understanding how force is produced to shape
      membranes by mechano-sensitive, processive barbed end tracking machineries like
      formins and by WASP-Arp2/3 branched filament arrays. A combination of biochemical
      and biophysical approaches, including bulk solution assembly measurements using
      pyrenyl-actin fluorescence, single filament dynamics, single molecule
      fluorescence imaging and reconstituted self-organized filament assemblies, have
      provided mechanistic insight into the role of actin polymerization in motile
      processes. 

PMID- 25948417
TI  - Atg1 family kinases in autophagy initiation.
AB  - Autophagosome formation, a landmark event in autophagy, is accomplished by the
      concerted actions of Atg proteins. Among all Atg proteins, Atg1 kinase in yeast
      and its counterpart in higher eukaryotes, ULK1 kinase, function as the most
      upstream factor in this process and mediate autophagy initiation. In this review,
      we summarize current knowledge of the structure, molecular function, and
      regulation of Atg1 family kinases in the initiation of autophagy. 

PMID- 25948418
TI  - Risk Factors for Gambling Problems: An Analysis by Gender.
AB  - Differences in problem gambling rates between males and females suggest that
      associated risk factors vary by gender. Previous combined analyses of male and
      female gambling may have obscured these distinctions. This study aimed to develop
      separate risk factor models for gambling problems for males and for females, and
      identify gender-based similarities and differences. It analysed data from the
      largest prevalence study in Victoria Australia (N = 15,000). Analyses determined
      factors differentiating non-problem from at-risk gamblers separately for women
      and men, then compared genders using interaction terms. Separate multivariate
      analyses determined significant results when controlling for all others.
      Variables included demographics, gambling behaviour, gambling motivations, money
      management, and mental and physical health. Significant predictors of at-risk
      status amongst female gamblers included: 18-24 years old, not speaking English at
      home, living in a group household, unemployed or not in the workforce, gambling
      on private betting, electronic gaming machines (EGMs), scratch tickets or bingo,
      and gambling for reasons other than social reasons, to win money or for general
      entertainment. For males, risk factors included: 18-24 years old, not speaking
      English at home, low education, living in a group household, unemployed or not in
      the workforce, gambling on EGMs, table games, races, sports or lotteries, and
      gambling for reasons other than social reasons, to win money or for general
      entertainment. High risk groups requiring appropriate interventions comprise
      young adults, especially males; middle-aged female EGM gamblers; non-English
      speaking populations; frequent EGM, table games, race and sports gamblers; and
      gamblers motivated by escape. 

PMID- 25948420
TI  - Ventricular assist devices for treatment of acute heart failure and chronic heart
      failure.
AB  - Despite therapeutic advances that improve longevity and quality of life, heart
      failure (HF) remains a relentless disease. At the end stage of HF, patients may
      become eligible for mechanical circulatory support (MCS) for the indications of
      stabilising acute cardiogenic shock or for chronic HF management. MCS use is
      growing rapidly in the USA and some countries of the European Union, especially
      in transplant-ineligible patients. In others, it remains largely a tool to
      stabilise patients until heart transplant. MCS comprises a heterogeneous group of
      temporary and durable devices which augment or replace the pumping function of
      one or both ventricles, with postimplant 2 year survival rivalling that of
      transplant in selected, lower-risk patients. In transplant-eligible and non
      transplant-eligible patients, improvement in end-organ perfusion, functional
      capacity and quality of life have been noted. Even for optimal candidates,
      however, there are a host of potential complications that require constant
      vigilance of a coordinated care team. Recently, there has been official
      recognition of the importance of palliative care expertise in advance care
      planning preimplant and management of patients with ventricular assist devices at
      the end of their lives.

PMID- 25948422
TI  - Expedited discharge with high-sensitivity (hs) troponin.

PMID- 25948421
TI  - Antiplatelet therapy following transcatheter aortic valve implantation.
AB  - OBJECTIVE: There is limited evidence to support decision making on antiplatelet
      therapy following transcatheter aortic valve implantation (TAVI). Our aim was to
      assess the efficacy and safety of aspirin-only (ASA) versus dual antiplatelet
      therapy (DAPT) following TAVI. METHODS: We performed a systematic review and
      pooled analysis of individual patient data from 672 participants comparing single
      versus DAPT following TAVI. Primary endpoint was defined as the composite of net
      adverse clinical and cerebral events (NACE) at 1 month, including all-cause
      mortality, acute coronary syndrome (ACS), stroke, life-threatening and major
      bleeding. RESULTS: At 30 days a NACE rate of 13% was observed in the ASA-only and
      in 15% of the DAPT group (OR 0.83, 95% CI 0.48 to 1.43, p=0.50). A tendency
      towards less life-threatening and major bleeding was observed in patients treated
      with ASA (OR 0.56, 95% CI 0.28 to 1.11, p=0.09). Also, ASA was not associated
      with an increased all-cause mortality (OR 0.91, 95% CI 0.36 to 2.27, p=0.83), ACS
      (OR 0.5, 95% CI 0.05 to 5.51, p=0.57) or stroke (OR 1.21; 95% CI 0.36 to 4.03,
      p=0.75). CONCLUSIONS: No difference in 30-day NACE rate was observed between ASA
      only or DAPT following TAVI. Moreover, a trend towards less life-threatening and
      major bleeding was observed in favour of ASA. Consequently the additive value of
      clopidogrel warrants further investigation.

PMID- 25948423
TI  - Is sunitinib-induced hypothyroidism a predictive clinical marker for better
      response in metastatic renal cell carcinoma patients?
AB  - BACKGROUND: The main goal of this study was to examine whether the occurrence of
      hypothyroidism during sunitinib therapy in patients with metastatic renal cell
      carcinoma (mRCC) is associated with a better outcome. METHODS: The study enrolled
      81 patients with pathologically proven mRCC who were treated with sunitinib
      between March 2008 and June 2013.Thyroid function evaluation comprised (free
      thyroxine) FT4 and thyroid-stimulating hormone (TSH) before treatment and at day
      1 of each 6-week cycle. Survival analysis was performed using the Kaplan-Meier
      method, and the differences among the groups were determined using the log-rank
      test. RESULTS: Hypothyroidism occurred in 30 (37%) of 81 patients within a median
      3 months (range 1-18) of treatment initiation. There was a statistically
      significant correlation between the occurrence of hypothyroidism during treatment
      and the rate of objective remission (ORR) (hypothyroid patients vs euthyroid
      patients: 46.7 vs 13.7%, respectively; P = 0.001). Median progression-free
      survival (PFS) was 10 (95% CI 6.13-13.8) months in the euthyroid patients, and 17
      (95% CI 9.33-24.6) months in the hypothyroid patients (P = 0.001). The median
      overall survival (OS) was 39 (95% CI 25.4-52.5) months in the hypothyroid
      patients and 20 (95% CI 14.7-25.2) months in the euthyroid patients (P = 0.019).
      CONCLUSIONS: The occurrence of hypothyroidism during treatment in patients was
      significantly associated with longer PFS, OS and better ORR in the current study.

PMID- 25948424
TI  - Comparison of chemical, biological and physical quality assessment of indoor
      swimming pools in Shahrekord City, Iran in 2013.
AB  - Previous studies have shown that mismanaged swimming pools could transmit water
      borne diseases. The objective of the present study was the quality assessment of
      chemical, biological and physical characteristics of swimming pools in Shahrekord
      city, southwest of Iran. The two main indoor swimming pools of Shahrekord city
      were considered during the summer and winter of 2013. The number of 459 samples
      were analysed from swimming pools, showers and dressing rooms for chemical,
      biological and physical quality assessment. The most prevalent fungi were
      Aspergillus (48.91%), Penicillium (22.9%), Nocardia (11.31%), Cladosporium
      (8.41%). Rhizopus (6.18%), Scopulariopsis (6.21%), Fusarium (5.31%), and Mucor
      (1.38%). The most fungal contamination sites for both swimming pools were
      showers. Results showed that the values of total faecal coliform, Pseudomonas
      aeruginosa, Legionalla, Escherichia coli and Heterotrophic Plate Count (HPC) for
      both swimming pools exceeded the guidelines, except for Staphylococcus aureus.
      The correlation coefficient between bathers load and total faecal coliform,
      heterotrophic bacteria was 0.949. The turbidity, free residual chlorine, and
      hardness of both swimming pools were not compliance with standard guidelines.
      Therefore, the improvement of disinfection and cleaning procedures is necessary,
      due to the different users and daily bather loads of each pool, as well as
      monitoring the water quality and increasing of the knowledge of swimming pool
      users on the risks of these potential diseases. 

PMID- 25948425
TI  - The perceived information in obtained from the informed consent in Iranian
      patients with cancer in clinical studies.
AB  - OBJECTIVE: One of the basic issues in clinical studies is to receive the informed
      consent; that is to say, all the activities applied in patient's involvement in
      the information, decision-making, ability and volunteering in diagnosis, cure and
      care. In as much as most cancer patients require information about their
      individual needs, the present study is conducted to determine the perceived
      information from the informed consent of clinical studies in cancer patients.
      METHODS: This is a descriptive study. Fifty cancer patients hospitalized for
      participating in the clinical study was chosen according to the convenience
      sampling. Tools used in this research included the questionnaire (individual and
      social features) and the check list about patient's right and cancer patient's
      information before and after receiving informed consent in clinical studies (10
      items on a Likert rating scale). To validate the study, content and formal
      validation was used. Data in this research were analyzed using descriptive
      statistics (frequency, mean and standard deviation) and the software of SPSS 16.
      RESULT: In general, the mean of the scores obtained from cancer patients'
      perceived information before completing the informed consent of the clinical
      studies was 14 +/- 3.5 and after consent of the clinical studies was 16 +/- 2.4.
      The cancer patients' perceived information before and after consent of the
      clinical studies was weak. CONCLUSIONS: Based on the findings of the present
      study, the rate of the information the cancer patients received, before
      completing the informed consent form, was low, but after completing the informed
      consent form this rate was again low. Therefore, conducting similar and wider
      studies is recommended to unveil the factors affecting perceiving information and
      how to promote the quality of the informed consent in other hospitals in Iran.

PMID- 25948426
TI  - Evaluation effect of shiatsu technique on labor induction in post-term pregnancy.
AB  - OBJECTIVES: Labor induction in post-term pregnancy is considered as a
      conventional process of mothers' care. Shiatsu technique is one of the
      complementary methods which use for post-term pregnancy induction. Therefore, the
      researchers decided to examine the effect of Shiatsu technique on the induction
      of post-term pregnancy. MATERIALS & METHODS: This is a randomized control trials
      which conducted on 288 women with post-term pregnancy who referred to consulting
      clinic at Ali- Ibn- Abi -Talib Hospital, in Zahedan-Iran in 2010-2011.
      Participants were selected based on random table. The participants divided into
      two groups: the first was shiatsu technique and the second group was control
      group (routine procedure). Shiatsu technique was conducted on the participants of
      intervention group for 30s on three points by an experienced midwife. The
      gathered data analyzed by SPSS version 15.00 and comparing tests were t-students
      tests, chi-square. RESULTS: Mothers ages range were between 16 to 42 years (mean
      26.5-5.7) in shiatsu and 17 to 43 years (mean 24.5-5.1) in control group.
      Regarding spontaneous initiation of labor, 82 women (56.9%) in Shiatsu group had
      spontaneous initiation of labor, whereas the number of women was only 12 (8.3%)
      in control group. Women who have used Shiatsu technique were significantly more
      likely to have spontaneous labour than those women who did not. CONCLUSIONS:
      Results of the study showed that shiatsu technique can be used as one of safe
      complementary methods for post-term pregnancy induction.

PMID- 25948427
TI  - Predictors of inappropriate hospital stay: experience from Iran.
AB  - OBJECTIVE: Hospital services are the most expensive component of modern health
      care systems and inappropriate hospital stay is one of the most important
      challenges facing hospitals in many countries. The purpose of this study was to
      determine the extent of inappropriate hospital stay and investigate the related
      factors in Semnan city (Iran). METHODS: In this study, the Iranian version of
      Appropriateness Evaluation Protocol (AEP) was used in a representative sample of
      300 hospital admissions and 905 hospital days. Data collection was performed
      during six weeks in January and February 2014 in four wards (two internal
      medicine and two surgical wards) of two hospitals in Semnan city (Iran). RESULTS:
      The results showed that 7.4% of admissions and 22.1% of stays have been
      inappropriate. Inappropriate stays were mainly concerned to the factors,
      including length of stay, inappropriate admissions, as well as factors related to
      hospitals. The most frequent causes of unjustifiable days were due to waiting for
      diagnostic or therapeutic procedures (35.1%), and 20.6% delay in discharge of
      patients by physicians due to conservative medical policy. CONCLUSION: In
      conclusion, this study confirms the existence of inappropriate hospital stays
      which may be due to patient characteristics and hospital factors. The most
      unjustifiable reasons for inappropriate hospital stay were related to internal
      processes of hospital, which mostly could be prevented through appropriate
      management Therefore, some steps must be taken to decrease inappropriate hospital
      stay and preserve hospital resources for patients who need them.

PMID- 25948428
TI  - Effect of increasing maximal aerobic exercise on serum muscles enzymes in
      professional field hockey players.
AB  - BACKGROUND & OBJECTIVES: Exercise results in oxidative enzyme increase and micro
      injuries in skeletal muscles. The aim of this study was to investigate the effect
      of maximal aerobic exercise on serum muscle enzymes in professional field hockey
      players. This study aims to determine the effect of increasing maximal aerobic
      exercise on creatine kinase (CK), creatine kinase-MB (CK-MB), aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT) serum levels. MATERIAL
      & METHODS: 31 young professional field hockey players (13 female and 18 male
      players) volunteered for this study. All participants underwent the shuttle run
      test. Blood samples were taken from each participant before the shuttle run test.
      Post test blood samples were taken immediately after exercise and one hour after
      respectively. Pre and post test CK, CK-MB, AST and ALT values were measured by
      means of auto analyzer using original kits. RESULTS: The acute post test measure
      of the CK level increased in male (p=0.002) and female (p=0.00) sportsmen. CK-MB
      values obtained one hour after the exercise was lower than those before the
      exercise in males (p=0.02). In females (p=0.017) and males (p=0.05) AST activity
      significantly increased immediately after exercise and decreased to resting
      activity 1 h recovery. ALT significantly increased immediately after exercise in
      female (p=0.03) and male (p=0.00) athletes and after 1 h recovery ALT activities
      decreased below resting values. CONCLUSION: The timing and severity of exercise
      used in our study increased CK values, decreased CK-MB values and AST, ALT values
      increased in female and male field hockey players.

PMID- 25948429
TI  - Interaction of lifestyle and work ability index in blue collar workers.
AB  - BACKGROUND: Early labor force exit is one of the major problems worldwide. The
      present study investigates the relationship between work ability and lifestyle.
      METHODS: This study was conducted at a manufacturing plant in Tehran in 2012. All
      851 male workers in this plant were included into the study and their work
      ability was assessed using the Work Ability Index (WAI). Based on the obtained
      scores, the participants were then classified into four work ability groups
      (poor, moderate, good, or excellent). Moreover, the participants' lifestyles were
      studied in three areas, including physical activity, cigarette smoking, and Body
      Mass Index (BMI). RESULTS: The average work ability index score was 42.07,
      ranging from 7-48. Among the participants, 6.4% (43), 6.5% (44), 38.3% (259), and
      48.8% (330) were in the groups with poor, moderate, good, and excellent work
      ability, respectively. The results of logistic regression analysis showed that
      there is a significant relationship between work ability and lifestyle (cigarette
      smoking, BMI, and physical activity) even after adjustment for confounding
      variables (P<0.05). CONCLUSIONS: According to the results of the present study,
      there might be a relationship between work ability and lifestyle (physical
      activity, BMI, cigarette smoking). Therefore, it is recommended to implement a
      lifestyle quality enhancement program to improve work ability in working
      environments.

PMID- 25948430
TI  - Development and psychometric evaluation of the nursing instructors' clinical
      teaching performance inventory.
AB  - Evaluation of nursing instructors' clinical teaching performance is a
      prerequisite to the quality assurance of nursing education. One of the most
      common procedures for this purpose is using student evaluations. This study was
      to develop and evaluate the psychometric properties of Nursing Instructors'
      Clinical Teaching Performance Inventory (NICTPI). The primary items of the
      inventory were generated by reviewing the published literature and the existing
      questionnaires as well as consulting with the members of the Faculties Evaluation
      Committee of the study setting. Psychometric properties were assessed by
      calculating its content validity ratio and index, and test-retest correlation
      coefficient as well as conducting an exploratory factor analysis and an internal
      consistency assessment. The content validity ratios and indices of the items were
      respectively higher than 0.85 and 0.79. The final version of the inventory
      consisted of 25 items, and in the exploratory factor analysis, items were loaded
      on three factors which jointly accounting for 72.85% of the total variance. The
      test-retest correlation coefficient and the Cronbach's alpha of the inventory
      were 0.93 and 0.973, respectively. The results revealed that the developed
      inventory is an appropriate, valid, and reliable instrument for evaluating
      nursing instructors' clinical teaching performance.

PMID- 25948431
TI  - Diagnostic value of Amsel's clinical criteria for diagnosis of bacterial
      vaginosis.
AB  - INTRODUCTION: Bacterial vaginosis (BV) is one of the most prevalent infections in
      women of reproductive age. Amsel's criteria and Nugent scoring system are among
      the most commonly used diagnostic methods. Although Nugent scoring system is
      considered the gold standard for diagnosing BV, it is time consuming and costly,
      and its interpretation needs lab equipment and experts. Hence, most physicians
      are inclined to use simpler clinical criteria that are yet accurate instead.The
      present study aimed to determine the diagnostic value of Amsel's criteria in
      diagnosing BV. MATERIALS & METHODS: This present study was conducted to validate
      diagnostic tests of BVin 120 married women in 2013. Amsel's criteria and Nugent
      scoring system were used to diagnose BV. Nugent scoring system was considered the
      gold standard and sensitivity, specificity, positive predictive value and
      negative predictive value of Amsel's criteria were compared with those of Nugent
      scoring system. RESULTS: Kappa coefficient was used to assess the diagnostic
      value of Nugent scoring system and Amsel's criteria. Kappa coefficient was found
      0.8, which confirms the reliability of both diagnostic methods. McNemar test did
      not reveal a significant difference between Nugent scoring system and Amsel's
      criteria in terms of diagnosing BV. As compared to Nugent scoring system, Asmel's
      criteria enjoy sensitivity of 0.91, specificity of 0.91, positive predictive
      value of 0.86, negative predictive value of 0.94, and accuracy of 0.91.
      CONCLUSION: If lab equipment is not available for diagnosing BV, Amsel's criteria
      can be as good as Nugent scoring system at diagnosing this infection.

PMID- 25948432
TI  - The effect of performance-based financial incentives on improving health care
      provision in Burundi: a controlled cohort study.
AB  - To strengthen the health care delivery, the Burundian Government in collaboration
      with international NGOs piloted performance-based financing (PBF) in 2006. The
      health facilities were assigned - by using a simple matching method - to begin
      PBF scheme or to continue with the traditional input-based funding. Our objective
      was to analyse the effect of that PBF scheme on the quality of health services
      between 2006 and 2008. We conducted the analysis in 16 health facilities with PBF
      scheme and 13 health facilities without PBF scheme. We analysed the PBF effect by
      using 58 composite quality indicators of eight health services: Care management,
      outpatient care, maternity care, prenatal care, family planning, laboratory
      services, medicines management and materials management. The differences in
      quality improvement in the two groups of health facilities were performed
      applying descriptive statistics, a paired non-parametric Wilcoxon Signed Ranks
      test and a simple difference-in-difference approach at a significance level of
      5%. We found an improvement of the quality of care in the PBF group and a
      significant deterioration in the non-PBF group in the same four health services:
      care management, outpatient care, maternity care, and prenatal care. The findings
      suggest a PBF effect of between 38 and 66 percentage points (p<0.001) in the
      quality scores of care management, outpatient care, prenatal care, and maternal
      care. We found no PBF effect on clinical support services: laboratory services,
      medicines management, and material management. The PBF scheme in Burundi
      contributed to the improvement of the health services that were strongly under
      the control of medical personnel (physicians and nurses) in a short time of two
      years. The clinical support services that did not significantly improved were
      strongly under the control of laboratory technicians, pharmacists and non-medical
      personnel. 

PMID- 25948433
TI  - Latent syphilis among inpatients in an urban area of China.
AB  - We aimed at investigating the epidemiological features of latent syphilis among
      inpatients in an urban area of China. During the period of Jan 1999 to Dec 2007,
      146 inpatients were positive for treponema pallidum particle agglutination (TPPA)
      assay from 22,454 inpatients who were admitted to the China Meitan General
      Hospital. The number of latent syphilis increased steadily during this period of
      time. From the 146 TPPA positive inpatients, 137 inpatients were diagnosed as
      latent syphilis. The number of male patients with latent syphilis was slightly
      more than the female, but there was no statistical significance (P>0.01). The
      number of male patients over 60 years old was 42 (30.66%), which was higher than
      other age groups (p<0.05). The number of female patients at the age range of 20
      29 years was 20 (14.60%), which was higher than other age groups (p<0.05). Our
      results demonstrated that routine syphilis screening among inpatients proves to
      be one of the most effective precautionary measures to identify latent syphilis
      and thus to prevent transmission in urban areas in China. 

PMID- 25948434
TI  - The prevalence of violence against Iranian women and its related factors.
AB  - BACKGROUND: Domestic violence against women is a public health problem with
      negative consequences, and it is an intractable and widespread problem. This type
      of violence affects the stability of the family. AIM: The aim of this study was
      to estimate the prevalence of any violence against women referring to health
      centers and explore the associated risk factors with violence in Ahvaz, Iran.
      METHODS: A cross-sectional study was conducted on randomly chosen samples of 368
      married women aged between 15-55 years in 2013. The samples were divided to two
      groups, with abused experience and without abused experience. The data were
      amassed by questionnaire form. RESULTS: The prevalence of violence against women
      was found to be around 63.8%, among them 58.8% were emotional abuse. The majority
      of women (84%) had never gone to a counseling center. Findings show 47%  of women
      were silent, 27% got in a fight, 7% screamed, 6% abused their children, and 5%
      threw things when occurred violence against them. Experience of violence in women
      correlated with the marriage age of woman, numbers of children, and difference of
      marriage age between couple, marriage age of men, employed women, uneducated
      women and the rate of drugs use in their husbands. CONCLUSIONS: Nurses and other
      health care providers can and should play a major role in empowering women living
      with violence and promote education, social policies and attitudes that
      proactively prevent violence.

PMID- 25948435
TI  - Gray-scale vs. color doppler ultrasound in cold thyroid nodules.
AB  - We intended to compare gray-scale vs. color Doppler ultrasound findings in cold
      thyroid nodules. Sixty-four patients with cold thyroid nodules for whom the
      presumptive diagnosis of malignancy (based on isotope scan study) had been made
      were consecutively included. They underwent gray-scale and color Doppler
      sonography studies. Based on histopathologic examination of surgically removed
      nodules, there were respectively 25 (39%) and 39 (61%) malignant and benign
      nodules. On color Doppler sonography, preference central hypervascularity was the
      most common finding in malignant nodules (17 nodules, 68%). Among benign nodules,
      preference perinodular hypervascularity was the most common finding (26 nodules,
      66.7%). The most sensitive and specific Doppler sonography findings for malignant
      nodules were preference central hypervascularity (68%) and only central
      vascularity (97%), respectively. On gray-scale sonography, absent halo sign was
      the most common finding in malignant nodules (20 nodules, 80%). Among benign
      nodules, microcalcification was the most common finding which was reported in 12
      nodules (30.7%). Hypoechogenicity was the most specific finding (76.9%) for
      malignant nodules. Since both gray-scale and color Doppler ultrasonography are
      inexpensive, non-invasive, and accessible methods to diagnose thyroid malignant
      cold nodules, it is recommended that these methods be applied by clinicians to
      assist or even substitute other invasive methods. 

PMID- 25948436
TI  - Reliability and validity of the workplace social distance scale.
AB  - Self-stigma, defined by a negative attitude toward oneself combined with the
      consciousness of being a target of prejudice, is a critical problem for
      psychiatric patients. Self-stigma studies among psychiatric patients have
      indicated that high stigma is predictive of detrimental effects such as the delay
      of treatment and decreases in social participation in patients, and levels of
      self-stigma should be statistically evaluated. In this study, we developed the
      Workplace Social Distance Scale (WSDS), rephrasing the eight items of the
      Japanese version of the Social Distance Scale (SDSJ) to apply to the work setting
      in Japan. We examined the reliability and validity of the WSDS among 83
      psychiatric patients. Factor analysis extracted three factors from the scale
      items: "work relations," "shallow relationships," and "employment." These factors
      are similar to the assessment factors of the SDSJ. Cronbach's alpha coefficient
      for the WSDS was 0.753. The split-half reliability for the WSDS was 0.801,
      indicating significant correlations. In addition, the WSDS was significantly
      correlated with the SDSJ. These findings suggest that the WSDS represents an
      approximation of self-stigma in the workplace among psychiatric patients. Our
      study assessed the reliability and validity of the WSDS for measuring self-stigma
      in Japan. Future studies should investigate the reliability and validity of the
      scale in other countries. 

PMID- 25948437
TI  - The topical effect of grape seed extract 2% cream on surgery wound healing.
AB  - BACKGROUND: Reducing the wound healing time is crucial in wound as it lowers the
      chance of infection and decreases complications and cost. Grape seed extract has
      the ability to release endothelial growth factor and its topical application
      results in contraction and closure of the skin wound. Furthermore, it possesses
      antioxidant and antibacterial properties. In several studies it has been proved
      effective in animals. Therefore, due to low side effects and recognition of
      herbal medicine, we decided to evaluate the effect of grape seed extract 2%
      herbal cream on human skin lesions. MATERIALS: This study is a double blind
      clinical trial conducted on two groups of treatment and placebo. Surgery was
      performed on skin lesions such as skin tags and moles which were found on the
      neck, trunk and limbs (except for face). After enrollment and obtaining informed
      consent from participants, they were randomized into two groups of treatment and
      placebo. Excision of the lesions was done by surgical scissors. The lesions got
      restored by secondary intention method. After the first day of treatment, the
      patients were visited on the 3rd, 7th, 10th, 14th, and 21st day. Grape seed
      extract cream 2% was produced and coded by the Faculty of Pharmacy, Ahvaz
      University of Medical Sciences. In order to compare the two groups, T-test was
      used. For time assessing, analysis of variance with repeated measures was
      employed. RESULTS: The results showed complete repair of wounds averagely on day
      8 for the treatment group and on day 14 for the placebo group, which was clearly
      significant in terms of statistical difference (p=0.00). CONCLUSION:
      Proanthocyanidins in grape seed extract trigger the release of vascular
      endothelial growth factor and its topical application causes wound contraction
      and closure. Curing skin lesions with grape seed extract caused proliferation
      areas with protected boundaries in epithelium, increased cell density and
      increased deposition of connective tissue at the wound site which in general
      improves cellular structure in wound. In addition, its anti-inflammatory and anti
      microbial properties are effective in wound healing.

PMID- 25948438
TI  - Factors affecting job motivation among health workers: a study from Iran.
AB  - OBJECTIVE: Human resources are the most vital resource of any organizations which
      determine how other resources are used to accomplish organizational goals. This
      research aimed to identity factors affecting health workers' motivation in Shahid
      Beheshti University of Medical Sciences (SBUMS). METHOD: This is a cross
      sectional survey conducted with participation of 212 health workers of Tehran
      health centers in November and December 2011. The data collection tool was a
      researcher-developed questionnaire that included 17 motivating factors and 6
      demotivating factors and 8 questions to assess the current status of some
      factors. Validity and reliability of the tool were confirmed. Data were analyzed
      with descriptive and analytical statistical tests. RESULTS: The main motivating
      factors for health workers were good management, supervisors and managers'
      support and good working relationship with colleagues. On the other hand, unfair
      treatment, poor management and lack of appreciation were the main demotivating
      factors. Furthermore, 47.2% of health workers believed that existing schemes for
      supervision were unhelpful in improving their performance. CONCLUSIONS:
      Strengthening management capacities in health services can increase job
      motivation and improve health workers' performance. The findings suggests that
      special attention should be paid to some aspects such as management competencies,
      social support in the workplace, treating employees fairly and performance
      management practices, especially supervision and performance appraisal.

PMID- 25948439
TI  - The facilitators and barriers to nurses' participation in continuing education
      programs: a mixed method explanatory sequential study.
AB  - BACKGROUND: Since several factors affect nurses' participation in Continuing
      Education, and that nurses' Continuing Education affects patients' and community
      health status, it is essential to know facilitators and barriers of participation
      in Continuing Education programs and plan accordingly. This mixed approach study
      aimed to investigate the facilitators and barriers of nurses' participation, to
      explore nurses' perception of the most common facilitators and barriers. METHODS:
      An explanatory sequential mixed methods design with follow up explanations
      variant were used, and it involved collecting quantitative data (361 nurses)
      first and then explaining the quantitative results with in-depth interviews
      during a qualitative study. RESULTS: The results showed that the mean score of
      facilitators to nurses' participation in Continuing Education was significantly
      higher than the mean score of barriers (61.99 +/- 10.85 versus 51.17 +/- 12.83;
      p<0.001, t=12.23). The highest mean score of facilitators of nurses'
      participation in Continuing Education was related to "Update my knowledge". By
      reviewing the handwritings in qualitative phase, two main levels of updating
      information and professional skills were extracted as the most common
      facilitators and lack of support as the most common barrier to nurses'
      participation in continuing education program. CONCLUSION: According to important
      role Continuing Education on professional skills, nurse managers should
      facilitate the nurse' participation in the Continues Education.

PMID- 25948440
TI  - The challenges and recommendations of accessing to affected population for
      humanitarian assistance: a narrative review.
AB  - OBJECTIVE: Access to affected people pays an important role in United Nation
      Organization for Coordination and Humanitarian Affairs (OCHA). The aim of this
      article is to identify the main obstacles of humanitarian access and the
      humanitarian organization responses to these obstacles and finally suggest some
      recommendations and strategies. METHODS: In this narrative study the researchers
      searched in different databases. This study focused on the data from five
      countries in the following areas: access challenges and constraints to affected
      population and response strategies selected for operations in the affected
      countries by humanitarian organizations. RESULTS: Three main issues were studied:
      security threats, bureaucratic restrictions and indirect constraint, which each
      of them divided to three subcategories. Finally, nine related subcategories
      emerged from this analysis. CONCLUSION: Most of these constraints relate to
      political issues. Changes in policy structures, negotiations and advocacy can be
      recommended to solve most of the problems in access issues.

PMID- 25948441
TI  - The impact of depression and malnutrition on health-related quality of life among
      the elderly Iranians.
AB  - INTRODUCTION: The present study aimed to assess the association between
      nutritional status and depressive symptoms among elderly Iranians and to explore
      their impact on their Health-Related Quality of Life (HRQoL). METHODS: In this
      cross-sectional study, 447 elders aging from 55 to 85 years were randomly
      selected and completed the Iranian version of Geriatric Depression Scale-15
      (GDS), Mini Nutritional Assessment (MNA), and the Iranian version of Short Form
      Health Survey (SF-36). RESULTS: Out of the 447 elderly, 72.1% were female with
      the mean age of 65.99 +/- 7.89 years. The prevalence of depression was 38.1%. In
      addition, the SF-36 sub-scores tended to be lower among the elders with
      depressive symptoms according to GDS. The Physical Functioning (PF), Bodily Pain
      (BP), Role Physical (RP), Role Emotional (RE), and Mental Health (MH) dimensions
      of the SF-36 were also statistically poorer in the elders with depression. The
      mean MNA score was 24.6 +/- 2.7; 35.4% of the participants were malnourished or
      at risk of malnutrition and 64.6% were adequately nourished. The sub scores of SF
      36 were significantly lower in the elders with impaired nutritional status.
      CONCLUSIONS: Considering the importance of the association among psychological
      and nutritional problems and HRQoL in caring for and promoting the welfare of the
      elders, this study provided fundamental information and a basis for further
      evaluation of this issue in developing and undeveloped countries.

PMID- 25948442
TI  - Translation of the fear avoidance beliefs questionnaire into Hausa language.
AB  - BACKGROUND: Self-report measures of fear-avoidance beliefs are widely used in
      clinical practice and research. To date there is no Hausa version of the Fear
      Avoidance Beliefs Questionnaire (FABQ). This is important as the Hausa language
      is a widely spoken language in West Africa. OBJECTIVES: The purpose of this study
      was to translate and validate the Hausa version of the FABQ in patients with non
      specific neck pain. METHODS: Two independent bilingual Hausa translators
      translated the English version of the FABQ into Hausa which was thereafter back
      translated by one independent bilingual translator. A professional expert panel
      revised the translations to produce a consensus version. The psychometric testing
      of the final translated instrument was investigated by surveying 54 Hausa
      speaking patients with chronic non-specific neck pain. Cross-sectional construct
      validity was evaluated by comparing Hausa Fear Avoidance Beliefs Questionnaire
      (FABQ-H) with the English version of the FABQ. Internal consistency of the FABQ-H
      was examined by Cronbach alpha by comparing the scores between the FABQ-H and its
      subscales. Test-retest reliability was evaluated by administering the Hausa
      version twice. RESULTS: The translated Hausa version of FABQ proved to be
      acceptable. The FABQ-H showed strong correlations (r=0.94, p=0.000) with the
      original English version. There was also high internal consistency between the
      FABQ-H and its subscales (physical activity component-alpha=0.88, p=0.000 and
      work component- alpha=0.94, p= 0.000). The FABQ-H also showed a high test-retest
      reliability (intra-class correlation coefficient =0.98). CONCLUSION: The FABQ-H
      demonstrated excellent psychometric properties similar to other existing
      versions. The FABQ-H is recommended for clinical practice.

PMID- 25948443
TI  - The burden of diabetes in Argentina.
AB  - OBJECTIVE: To measure the economic burden of diabetes in Argentina by age, gender
      and region for the year 2005, in disability-adjusted life years (DALYs). METHODS:
      DALYs were estimated by the sum of years of life lost due to premature death
      (YLL) and years of life lived with disability (YLD). RESULTS: In the population
      studied (20 to 85 years), the burden of diabetes without complications was 1.3
      million DALYs, 85% of which were caused by disabilities. Whereas mortality rates
      (YLL) increased as a function of age, YLD showed the opposite relationship. Women
      had higher burden of disease values, represented by 51 and 61% of YLL and YLD,
      respectively, independently of age. CONCLUSIONS: Our results demonstrate that
      disabilities are a key component of diabetes burden; its regular and systematic
      estimation would allow to design effective prevention strategies, to assess the
      impact of their implementation and to optimize resource allocation based on
      objective evidence.

PMID- 25948444
TI  - An investigation of the socio-economic status of the addicts in Lashar and
      Nikshahr county and its comparison with ordinary.
AB  - The world today is threatened by great disasters and catastrophes and one of the
      greatest of them is addiction. Addiction is a disaster that threatens all age and
      sex groups. For instance, in our country more than 2% of people are addicted. In
      this study, two groups of addicted (170) and healthy (167) individuals that had
      been selected in the systematic random method, were investigated in terms of the
      socio-economic status. The data was collected through the questionnaire. The
      average age and education level were 34.8 and 4.22 respectively among the
      addicted and 31.27 and 6.3 respectively among the healthy individuals. 83.1% of
      the addicted and 74.7% of the healthy individuals were married. A significant
      difference was observed between the education level and addiction with the p=0
      using the t-test. A significant relationship was observed between the existence
      of addiction in the family with the p=0 and addiction among friends and addiction
      with the p=0.0001 and between job and addiction with the p=0.0115 and between
      addiction and the level of income with the p=0.0065. 

PMID- 25948445
TI  - The effect of an education-based intervention on self-reported awareness and
      practice of Iranian nurses in observing patients' rights.
AB  - BACKGROUND: For patients' rights to be observed, first patients and health care
      providers should be aware of these rights. Nurses' lack of awareness of these
      rights leads to their inability to recognize patients' legal and ethical issues,
      and reduces the quality of provided services. This study was conducted to
      determine the effect of an education-based intervention on self-reported
      awareness and practice of nurses in observing patients' rights. METHODS: In this
      quasi-experimental study, awareness and practice of 90 nurses on Patient's Bill
      of Rights were examined in case and control groups, before, 2 and 4 weeks after
      an educational intervention program on. Participants were selected from teaching
      hospitals of Mazandaran University of Medical Sciences, Iran. Data was gathered
      using the valid and reliable 21-item questionnaire in a 3-point Likert scale
      during a 5-month period from October 2013 to March 2014. For data analysis,
      descriptive statistical methods, paired t-test, and repeated measure analysis of
      variance at significant level P<0.05 were used. RESULTS: Participants' mean age
      and work experience were found 37.1 +/- 5.71 years and 11.76 +/- 5.99 years
      respectively. Mean scores of nurses' awareness and practice before intervention
      were 15.12 +/- 2.19 and 9.13 +/- 2.36, accordingly. Repeated measure analysis of
      variance test showed a significant difference in awareness and practice of nurses
      before and after intervention (P<0.001). CONCLUSION: Enhancing nurses' awareness
      on Patient's Bill of Rights through revision of educational curriculum in nursing
      schools, together with considering appropriate relevant content in continuous
      education programs in health systems can lead to improved quality of nursing care
      services.

PMID- 25948446
TI  - Information technology governance domains in hospitals: a case study in Iran.
AB  - IT governance is a set of organizational structures ensuring decision-making
      rights and responsibilities with regard to the organization's IT assets. This
      qualitative study was carried out to identify the IT governance domains in
      teaching hospitals affiliated to Iran University of Medical Sciences. There were
      10 heads of IT departments and 10 hospital directors. Semi structured interviews
      used for data collection. To analyze the data content analysis was applied. All
      the interviewees (100%) believed that decisions upon hospital software needs
      could be made in a decentralized fashion by the IT department of the university.
      Most of the interviewees (90%) believed that there were policies for logistics
      and maintenance of networks, purchase and maintenance, standards and general
      policies in the direction of the policies of the ministry of health and medical
      education. About 80% of the interviewees believed that the current emphasis of
      the hospital's IT unit and the hospital management for outsourcing of services
      were in the format of specialized contracts and under supervision of the
      university Statistic and IT department. A hospital strategic committee is an
      official organizational group consisting of hospital executives, heads of IT and
      multiple functional areas and business units in a hospital. In this committee,
      "the head of hospital" acts as the director of IT activities and ensures that IT
      strategies are alignment with the hospital business strategies.

PMID- 25948447
TI  - Treatment outcome in chronic hepatitis C infection: a four years survey among
      Iranian patients.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection is universal. Side effects of its
      treatment are observed in many patients. The present study was designed to
      evaluate treatment outcome and side effects of the treatment in chronic HCV
      infection. MATERIALS & METHODS: The current study was conducted prospectively on
      patients with hepatitis C infection. They had been treated with the standard drug
      regimen, if indicated. They were followed for treatment response, side effects of
      therapy, and its related factors. FINDINGS: From ninety one patients, eighty four
      persons finished their treatment course. They comprised 71 (84.5%) males and 13
      (15.5%) females. Their mean age was 41.5 +/- 11.90 years (20-69 years). Genotype
      3 was the most common virus genotype (51.2%). Sustained virologic response (SVR)
      was 84.5% for genotype 3 and 47.5% for genotype 1. Decrease in hemoglobin (43%),
      weakness and fatigue (26%), neutropenia (13%), and thrombocytopenia (13%) were
      the most common side effects of the treatment. Seven patients can not finish
      their treatment course, because of the side effects. CONCLUSION: Genotype 3,
      viral load less than 600000, and more than 3- fold rise in AST are associated
      with higher SVR. Early administration of the added drugs such as erythropoietin
      and G-CSF to not reduce the drug doses were also influential.

PMID- 25948448
TI  - Association between short sleep and body mass index, hypertension among acute
      coronary syndrome patients in coronary care unit.
AB  - INTRODUCTION: Patients with coronary diseases admitted to special care unit often
      suffer from sleep disorders, which may cause physiological changes and adversely
      affect patient's health. The relationship between sleep disorders and obesity is
      an important factor in studies on sleep disorders and other chronic diseases in
      all groups, including cardiovascular diseases. Understanding this relationship
      may increase the chance of progress in effective medical interventions in sleep
      disorders and obesity. This study was designed to evaluate the association
      between short sleep and Body Mass Index (BMI), hypertension among acute coronary
      syndrome patients. MATERIALS & METHODS: In this descriptive analytical study, 221
      coronary patients admitted to coronary care unit and general wards were
      investigated. Data were collected through a researcher-made questionnaire whose
      validity and reliability had been confirmed. Data were analyzed with SPSS-16
      software. RESULTS: A total of 221 patients with acute coronary diseases
      (including myocardial infarction and angina pectoris) with a mean age of 61.27
      years were studied, of whom 61.5% were male and 38.5% were female. A significant
      association was observed between short sleep and higher BMI (P=0.000). About half
      the patients (49.3%) had a history of hypertension, and sleep disorders were also
      significantly related to hypertension (P=0.006). DISCUSSION: In this study, sleep
      disorders were patients' main complaint. Researchers found that patients with
      less than 5 hours or more than 9 hours sleep at night were more likely to have
      hypertension compared to patients that slept 7-8 hours. Lack of sleep affects
      metabolism, and daily energy expenditure reduces with increased immobility. In
      this study, a significant relationship was observed between BMI and sleep
      duration among hospitalized patients in coronary care unit (P=0.000), and sleep
      disorders increased with higher BMI. Short of sleep increases sympathetic tonus,
      cortisol level, and activation of inflammatory pathways, impairing glucose
      metabolism and contributing to overweigh, increased visceral fat. CONCLUSION: Our
      findings suggest that poor sleep quality, is related to higher BMI and
      hypertension among acute coronary syndrome patients.

PMID- 25948449
TI  - Relationship between family functioning and mental health considering the
      mediating role of resiliency in type 2 diabetes mellitus patients.
AB  - This study was aimed at describing the mediating role of resiliency in the
      relationship between family functioning and mental health in patients with type 2
      diabetes mellitus. This descriptive research was a correlational study. A total
      of 225 individuals were chosen by simple random sampling technique from type 2
      diabetic patients presented to diabetes care centers in Kermanshah in 2014 in
      Iran. The 12-item General Health Questionnaire (GHQ-12), the Family Assessment
      Device (FAD) and the Resilience Scale (CD-RISC) were used to collect the required
      data. The collected data were analyzed using the Pearson's correlation test and
      To study the mediating role of resiliency in family functioning and mental health
      interaction, the path analysis method was applied. The results showed that there
      is a relationship between family functioning, resilience and mental health.
      Resilience plays a mediating role between family functioning and mental health.
      Therefore, paying attention to resilience in patients may lead to improving
      mental health in diabetic patients. 

PMID- 25948450
TI  - Family medicine in Iran: facing the health system challenges.
AB  - BACKGROUND: In response to the current fragmented context of health systems, it
      is essential to support the revitalization of primary health care in order to
      provide a stronger sense of direction and integrity. Around the world, family
      medicine recognized as a core discipline for strengthening primary health care
      setting. OBJECTIVE: This study aimed to understand the perspectives of policy
      makers and decision makers of Iran's health system about the implementation of
      family medicine in Iran urban areas. MATERIALS/PATIENTS & METHODS: This study is
      a qualitative study with framework analysis. Purposive semi-structured interviews
      were conducted with Policy and decision makers in the five main organizations of
      Iran health care system. The codes were extracted using inductive and deductive
      methods. RESULTS: According to 27 semi-structured interviews were conducted with
      Policy and decision makers, three main themes and 8 subthemes extracted,
      including: The development of referral system, better access to health care and
      the management of chronic diseases. CONCLUSION: Family medicine is a viable means
      for a series of crucial reforms in the face of the current challenges of health
      system. Implementation of family medicine can strengthen the PHC model in Iran
      urban areas. Attempting to create a general consensus among various stakeholders
      is essential for effective implementation of the project.

PMID- 25948451
TI  - An evaluation by elderly people living at home of the prepared meals distributed
      by their municipality - a study with focus on the Swedish context.
AB  - Prepared meals distributed by municipalities is a service to elderly people, or
      persons with health related impairments, who live in their own home, have
      difficulties preparing their own food and cannot meet their food requirements in
      any other way. This study aimed to provide a brief picture of how elderly people
      living at home perceive the food they receive through their municipal food
      service and what is important to them. The data was collected using
      questionnaires. 274 out of 276 participants answered the questionnaire (n=173
      women 62% and n=101 man 37%). The data was analyzed using Principal Component
      Analysis (PCA). The results showed that the elderly persons receiving meals
      through the service were often satisfied, especially with the size of the
      portions and the delivery time. Those who had been using the food delivery
      service for a longer time were not satisfied with the alternative dishes they
      were been offered. There was no significant difference between the views of
      either gender. Further, those who were receiving special food were, in general,
      unsatisfied with the meals delivered. Development of the food distribution
      service by systematic quality insurance and interactive knowledge exchange
      between the producers and consumers seems to be a way to promote a more holistic
      and individual adjusted service. Evaluation of the municipal FD service is a
      powerful tool that can contribute to the development of this service. The food
      service can be improved and consequently even the quality of life and health of
      its receivers. The present survey should be revisited and developed in order to
      detect differences between genders. 

PMID- 25948452
TI  - A researcher's self-reflection of the facilitation and evaluation of an action
      research project within the Swedish social and care context.
AB  - The AR's (Lewin, 1946) assumption was that human beings exist in life spaces
      through interaction, and communication, and that knowledge development is the
      result of changes in cognitive structures through communication and involvement
      in research processes. And further, from the construction of new knowledge gained
      by learning from each other, comes the presumption to change. The participation
      is described as "citizen power" (Arnstein, 1969), which means being included in
      the development process. The degree of citizen power is based on partnership,
      delegated power and citizen control. All these steps are positioned at the
      highest level when ranking participation. Partnership means engaging and
      negotiating with the high level decision makers. The result of delegated power is
      apparent when the negotiations result in achieving leading decisions that
      influence a particular plan or programme. 

PMID- 25948453
TI  - The gap in digestive organ cancers in Inner Mongolia, 2009-2012.
AB  - OBJECTIVES: The aim of this study was to explore the characteristics of digestive
      organ cancer mortality and the potential years of life lost in Inner Mongolia,
      and to provide evidence for the prevention of digestive organ cancers. METHODS:
      Using data from the Death Registry System from 2009 to 2012, we classified male
      and female cancer deaths according to the International Classification of Disease
      (10th revision). The mortality and potential years of life lost were calculated
      for digestive organ cancers in Inner Mongolia. The average years of life lost was
      calculated. RESULTS: Digestive organ cancer mortality in Inner Mongolia was
      higher in men than in women. The potential years of life lost were also much
      higher in men than in women. Gallbladder cancer, pancreatic cancer, and
      colorectal, anus, and anal canal cancer were the most prominent contributors to
      mortality. Esophageal cancer was the most prominent contributor to potential
      years of life lost, and was the leading cause of average years of life lost in
      both sexes. CONCLUSION: Liver cancer and stomach cancer mortality and the
      potential years of life lost to liver and stomach cancer are demonstrably higher
      in Inner Mongolia. Although esophageal cancer mortality was not the highest of
      the digestive organ cancers, the average years of life lost to esophageal was the
      highest for both sexes, and it should therefore be targeted for prevention.

PMID- 25948454
TI  - Theory-based interventions in physical activity: a systematic review of
      literature in Iran.
AB  - Lack of physical activity is ranked fourth among the causes of human death and
      chronic diseases. Using models and theories to design, implement, and evaluate
      the health education and health promotion interventions has many advantages.
      Using models and theories of physical activity, we decided to systematically
      study the educational and promotional interventions carried out in Iran from 2003
      to 2013.Three information databases were used to systematically select papers
      using key words including Iranian Magazine Database (MAGIRAN), Iran Medical
      Library (MEDLIB), and Scientific Information Database (SID). Twenty papers were
      selected and studied .Having been applied in 9 studies, The Trans Theoretical
      Model (TTM) was the most widespread model in Iran (PENDER in 3 studies, BASNEF in
      2, and the Theory of Planned Behavior in 2 studies). With regards to the
      educational methods, almost all studies used a combination of methods. The most
      widely used Integrative educational method was group discussion. Only one
      integrated study was done. Behavior maintenance was not addressed in 75% of the
      studies. Almost all studies used self-reporting instruments. The effectiveness of
      educational methods was assessed in none of the studies. Most of the included
      studies had several methodological weaknesses, which hinder the validity and
      applicability of their results. According to the findings, the necessity of need
      assessment in using models, epidemiology and methodology consultation, addressing
      maintenance of physical activity, using other theories and models such as social
      marketing and social-cognitive theory, and other educational methods like
      empirical and complementary are suggested. 

PMID- 25948455
TI  - Perception of Iranian middle-aged women regarding moral health concept: a content
      analysis.
AB  - INTRODUCTION: The present study aimed at exploring and describing the perception
      of moral health from middle-aged women standpoints. Women's decisive role in
      family is undeniable. In the family which is built upon tradition, faith and
      ethics, this is women's principle which is represented in the moral health of the
      individual and the society, deals with the nature of the vice and virtue. This
      study attempted to identify the perception of Iranian middle-aged women about the
      concept of moral health. METHOD: The present study completed through a content
      analysis method. Twenty two middle-aged women were recruited through purposive
      sampling. Data were granted by face to face, semi-structured interview. RESULT:
      Our major categories are devotion, preserving moral values and moral challenges.
      Devotion category includes subcategories such as prioritizing the health of
      family members and trying to save marriage. Preserving moral values category
      includes subcategories such as respecting values and consolidating beliefs over
      time. Moral challenges category consists of individual and familial challenges
      subcategories. CONCLUSION: Moral health is of high importance which affects
      various dimensions of individual, social and familial life. The findings of the
      present study presented new dimensions of middle-aged women's health regarding
      moral health which can finally have different consequences on familial and social
      moral health.

PMID- 25948456
TI  - An examination of marketing techniques used to promote children's vitamins in
      parenting magazines.
AB  - More than a third of children and adolescents in the United States take vitamins
      even though professional medical organizations do not endorse their use in
      healthy children. Regardless of their efficacy, children's vitamin products are
      aggressively promoted. Therefore, the goal of this study was to describe and
      analyze advertisements related to vitamins in the following three popular
      parenting magazines, Parents, Parenting Early Years, and Parenting School Years.
      A total of 135 magazines across four years were reviewed.  There were 207
      advertisements for children's vitamins, all in the form of chewy or gummy.  None
      of these advertisements included a dosage or a warning.  Almost all (92.3%)
      included a cartoon in the advertisement.  Almost a quarter (23.2%) of the
      advertisements promoted their product with the theme of prevention and more than
      half (51.2%) included the theme of peace of mind.  Parenting magazines are a
      popular medium for providing exposure to products geared towards children. 
      Companies that market children's vitamins in these magazines can increase
      awareness among parents of the risks by providing warning and dosage information
      in their advertisements.  Magazines can also play a role by encouraging
      responsible marketing and providing editorial content on children's vitamins and
      potential consequences of pediatric overdose. 

PMID- 25948457
TI  - A study of marital satisfaction among non-depressed and depressed mothers after
      childbirth in Jahrom, Iran, 2014.
AB  - INTRODUCTION: Birth is one of the most wonderful events in nature and pregnancy
      and delivery are major developments for most married women. Similar to the
      pregnancy period, the period of time following delivery is accompanied by certain
      mental and physical changes in women. During this time, mothers experience a full
      range of mental disorders, varying from minor to psychotic. The objective of this
      study was to examine marital satisfaction among non-depressed and depressed
      mothers who visited primary health centers in Jahrom after childbirth in 2014.
      MATERIALS & METHODS: This is a descriptive cross-sectional study. The study
      population consisted of 80 mothers, who were in the 6 to 12 weeks of delivery and
      had visited primary health centers in Jahrom from April to July, 2014.To select
      the participants, the researcher looked thorough the files at each center and
      chose the mothers who were qualified for the study based on convenience sampling.
      The criteria for participation were: being aged from 20 to 40; being in the 6-12
      weeks since delivery; having a healthy newborn; willingness to participate in the
      study. The participants were divided into the two groups of mothers suffering
      from postpartum depression (40 women) and mothers not affected by postpartum
      depression (40 women) on basis of questionnaire. The study follows the ethics in
      a scientific study. The researcher personally visited the primary health centers
      and explained the objectives of the study to the participants. Subsequently, the
      participants were asked to complete a demographic questionnaire, Enrich Marital
      Satisfaction Scale, and Edinburgh Postpartum Depression Scale. The participants
      were allowed one hour to complete the questionnaires. RESULTS: The results showed
      that the average age of depressed and non-depressed women was respectively 28.1
      +/- 5 and 29.4 +/- 5.5. Regarding the sex of the newborns, 53% of the depressed
      women had a son and 46.7% had a daughter. In the non-depressed group, 43.3% of
      the mothers had a son and 56.7% had a daughter. 56.7% of the depressed mothers
      were first-time mothers; however, 43.3% of the non-depressed mothers had
      experienced childbirth for the first time. Most of the women in both groups had a
      high-school diploma-53% of the depressed mothers and 51% of the non-depressed.
      66.7% of the depressed mothers had had natural childbirths; 60% of the non
      depressed mothers had had Cesareans. There was not a statistically meaningful
      difference between the two groups in terms of the demographic variables. The
      average depression score of the depressed group was 13.7 with a standard
      deviation of 3.2; the average depression score of the non-depressed group was 5.8
      with a standard deviation of 2. There was a statistically significant difference
      between the two groups in terms of marital satisfaction. CONCLUSION: Postpartum
      depression is a major and common health problem, affects many women after
      childbirth and inflicts not only direct costs on the health care system, but
      causes extensive indirect losses due to mothers' inability to function. Though
      this condition is prevalent among new mothers, not many researchers have
      addressed it in small towns and investigated its relationship with marital
      satisfaction. In addition, most women suffering from postpartum depression know
      very little about the disorder. Accordingly, it is vital to educate women and
      conduct more studies on the issue.

PMID- 25948458
TI  - Quality of life among Thai workers in textile dyeing factories.
AB  - The purpose of a cross-sectional study was to investigate factors influencing the
      quality of life among Thai workers in textile dyeing factories. Samples included
      205 Thai workers from five textile dyeing factories located in the suburban area
      of Bangkok in Thailand. Data were collected with a self-administered
      questionnaire. Scales of the questionnaire had reliability coefficients ranging
      from 0.70-0.91. The results revealed that the overall quality of life among
      workers was most likely between good and moderate levels, and the percentage-mean
      score was 74.77. The seven factors associated with the overall quality of life
      were co-worker relationships, safety at work in the dimension of accident
      prevention, job characteristics, supervisory relationships, welfares, marital
      status, and physical environment. Furthermore, co-worker relationships, accident
      prevention, and marital status were three considerable predictors accounted for
      23% of the variance in the overall quality of life among workers in textile
      dyeing factories. 

PMID- 25948459
TI  - Determinants of physical activity based on the theory of planned behavior in
      Iranian Military Staff's Wives: a path analysis.
AB  - Level of physical activity as a key determinant of healthy lifestyle less than is
      required in individuals particularly women. Applying theories of behavioral
      change about complex behaviors such as physical activity leads to identify
      effective factors and their relations. The aim of this study was to determine
      predictors of physical activity behavior based on the Theory of Planned Behavior
      in military staff's wives in Tehran. This cross-sectional study was performed in
      180 military personnel's spouses residing in organizational houses, in Tehran,
      Iran in 2014. The participants were randomly selected with multi-stage cluster
      sampling. The validity and reliability of the theory based scale evaluated before
      conducting the path analysis. Statistical analysis was carried out using SPSS16
      and LISREL8.8. The results indicated the model explained 77% and 17% of intention
      and behavior variance. Subjective norms (Beta=0.83) and intention (Beta=0.37)
      were the strongest predictors of intention and behavior, respectively. The
      instrumental and affective attitude had no significant path to intention and
      behavior. The direct relation of perceived behavioral control to behavior was non
      significant. This research demonstrated relative importance and relationships of
      Theory of Planned Behavior constructs in physical activity behavior of military
      personnel's spouses in Tehran. It is essential to consider these determinants in
      designing of educational interventions for promoting and maintaining physical
      activity behavior in this target group. 

PMID- 25948460
TI  - Systolic and diastolic dysfunction of the right heart ventricle in patients with
      chronic obstructive pulmonary disease in extremely cold climate.
AB  - The paper describes echocardiographic values of systolic and diastolic
      dysfunction the right heart ventricle in 229 patients with chronic obstructive
      pulmonary disease. In our patients the values AvPAP (?25 mmHg while resting),
      FDDrv and FSDrv (>26 and 20 mm respectively), the thickness of front wall the RV
      (>5 mm), the dimension of AD (>35 mm), as well as the reduction the vestibular
      distal shortening of RV (<23%), maximum blood velocity and the blood evacuation
      time from reflect indirectly the progressive reduction the contractive capacity
      RV myocardium and the occurrence of systolic dysfunction. In patients with severe
      de-compensation a restrictive type diastolic function is more characteristic -
      acceleration of early diastolic filling and blood velocity decrease during the
      auricular systole. 

PMID- 25948461
TI  - A study on factors that drive variation in the levels of social capital among
      people living with HIV/AIDS in Iran.
AB  - INTRODUCTION: Social capital is increasingly used in relation to health issues,
      particularly in sexually transmitted diseases/infections and health behaviors.
      Experiences indicated that social capital can contribute in changing HIV related
      risk behaviors and a decline of HIV infection through social groups and
      networking and make more effective use of HIV/AIDS prevention, care, and
      treatment services. We aimed to assess social capital in these persons through a
      quantitative study. METHOD: This cross-sectional study was performed with a
      convenience sample of 300 people living HIV/AIDS referred to a counseling center
      of behavioral diseases, in Imam Khomeini Hospital, in Tehran, the capital of
      Iran, during September 2011 to May 2012. Data collection tools were a demographic
      questionnaire and World Bank Social Capital Questionnaire (SC-IQ). The analysis
      of data was performed by the SPSS statistic software version 18. To identify
      factors influencing social capital in participations, Pearson correlation
      coefficient, ANOVA, t-test, and a multiple regression were applied. The
      significant level was considered 0.05 in this study. RESULTS: 165 (55%) were male
      and the rest female. The mean age of participants was 34.3 +/- 7.5. The mean
      score of total social capital was 2.34 +/- 0.5 in all participants. The domain of
      individual trust had the highest mean score (2.53 +/- 0.66). The lowest mean
      score was related to the domain of social trust and associative relations (2.23
      +/- 0.62). Variables such as ethnicity, age, and middle economic status had a
      significant impact on the domain of individual trust so that the mean score of
      this component of social capital was lower among women (0.396) than men. Factors
      affecting total social capital were ethnicity and middle economic status.
      CONCLUSION: Finding emphasized on the role of economic status, ethnicity and
      gender in persons living with HIV/AIDS. Thus recommended that policy makers and
      program managers consider social groups and networks, especially in women in the
      design and delivery of intervention strategies to reduce HIV transmission.

PMID- 25948462
TI  - A study on the factors affecting the prescription of injection medicines in Iran:
      a policy making approach.
AB  - BACKGROUND & AIM: Inappropriate prescribing injection medicines can reduce the
      quality of medical care, patient safety, and leads to a waste of resources.
      Sufficient evidence is not available in developing countries to persuade policy
      makers to promote rational drug prescription. The objective of this study is to
      assess some factors affecting the prescription of the injection medicines in
      Iran. METHODS: In this descriptive-analytic study, the data of 91,994,667
      selected prescription letters were collected by the Ministry of the Health and
      Medical Education (MOHME) throughout the country at the year 2011 which were
      analyzed through a logarithmic regression model. RESULTS: Results of the study
      show that the percentage of the prescription letters containing injection items
      varied from 27 percent (in Yazd) to 57 percent (in Ilam). Also the impact of
      price on the prescription of the injection medicines was not significant
      (P=0.55). But the impact of the prescription of antibiotics and corticosteroid on
      injections were significant (P>0.05) and equal 0.44 and 0.65 respectively.
      CONCLUSION: Increasing price of injection medicines as a policy towards reducing
      consumptions cannot be a successful policy. But reducing the use of antibiotics
      and corticosteroids can be a more effective policy to reduce the use of injection
      medicines.

PMID- 25948463
TI  - Hemoptysis: comparison of diagnostic accuracy of multi detector CT scan and
      bronchoscopy.
AB  - BACKGROUND: Hemoptysis is the expectorating of blood from the tracheobronchial
      tree or pulmonary parenchyma. There is conflicting information about usefulness
      of radiography, MDCT, and bronchoscopy for investigating site and cause of the
      bleeding in patients with hemoptysis. The present study attempted to evaluated
      efficacy of these methods for identifying hemoptysis' cause and etiology on 40
      patients with the disease. METHODS: A total of 40 patients with Hemoptysis who
      were referred to Golestan and Emam Khomeini hospitals were evaluated. Complete
      history of symptoms, volume and duration of Hemoptysis and demographic
      information were documented. Radiography, MDCT, and bronchoscopy were performed
      on all patients in order to investigate the site and cause of the bleeding.
      RESULTS: Results showed MDCT had higher efficacy in identifying bleeding site
      than radiography, while efficacy of radiography and bronchoscopy or efficacy of
      MDCT and bronchoscopy weren't significantly different. In addition, sensitivity
      of MDCT (60%) for detecting cause of the bleeding was higher than that of
      radiography (25%) and bronchoscopy (32.5%). CONCLUSION: The present study
      suggests MDCT as a suitable method in screening patients with hemoptysis, because
      it managed to detect site and causes of bleeding more efficiently than other
      methods. Additionally, we concluded that MDCT is an appropriate technique for
      diagnosing malignancies that cause hemoptysis in patients.

PMID- 25948464
TI  - A predictive model of apartment-living based on socio-economic and demographic
      factors with health-based approach in Iran.
AB  - OBJECTIVE: Due to importance and progressive growth of apartment-living
      phenomenon in the world today, it is essential to survey the different dimensions
      of this modern lifestyle. The aim of this study is to predict rate of apartment
      living based on the different predicted variables of socio-economic and
      demographic factors with approach to different health aspects. METHODS: A
      descriptive- analytic study was carried out between 600 apartment and 800 non
      apartment residents in the Shiraz (Southern Region of Iran) through multi-stage
      cluster sampling during the year 2011. The statistical analysis was performed on
      the obtained data using multi-variable logistic regression as well as ANOVA
      analysis. RESULT: the rate for apartment-living in above 30 years old age group
      was 8.31 times more than 15-30 years old, 9.6 times more in employed vs.
      unemployed; 6.57 and 9.49 times more in families with average and high monthly
      incomes, respectively, vs. family with low monthly income; 8.73 times more in
      owner sub-group vs. renter sub-group; and 1.30 times more in people living lonely
      than those living with family. People living in an apartment are in poor health
      status considering physical, mental and social aspects. CONCLUSION: Based on the
      results, it is very important that policy makers in urban areas consider the
      determinative role of socio-economic and demographic factors, which are involved
      in selecting apartment-living lifestyle by urban residents and also are effective
      on health.

PMID- 25948465
TI  - Assessment of nutritional status among adolescent boys in an urban population of
      South India.
AB  - BACKGROUND: Deficiency of calories and certain micronutrients is known to cause
      growth faltering in children and adolescents. It is recognized that varieties of
      foods need to be consumed in order to meet requirements for essential nutrients.
      Lack of diversity in the diets is a serious problem among poor populations in the
      developing world. The extent of variations in intake of nutrients occurring in a
      homogeneous population provides useful information. SUBJECTS & METHODS: This
      study investigates the mean intake of nutrient by 1083 adolescent males, age 10
      19 years, in comparison to the RDA values suggested by ICMR for Indians. Food
      intakes, social class and knowledge about health education were obtained by
      questionnaires. Descriptive statistics, non-parametric statistics, and Chi-Square
      tests were performed to and interpret the data, particularly hypothesis testing.
      RESULTS: Mean intake of calories varied from 1512 +/- 532 for pre-adolescent to
      1742 +/- 660 for post-adolescence, the differences in intake between pre
      adolescence to adolescence was statistically significant. The intake was largely
      different compared to the respective RDAs including proteins which were markedly
      lower than the RDA. The mean intake increased linearly with the advancing stages
      of adolescence. Intake of calcium by boys during pre-adolescence and adolescence
      stage were lower by 20-30% as compared to the RDA, whereas the post-adolescent
      boys were found to consume a fair amount and met their RDAs. Intakes of iron and
      ?-carotene were highly variable, the majority of the selected boys consumed much
      less than the RDAs. The differences in the intakes were statistically not
      significant. CONCLUSION: Mean intakes of nutrients indicate that the majority of
      the selected boys consumed protein, calories, iron, calcium and ? carotene in
      three stages of adolescent markedly lower than the respective RDAs. Family type,
      birth order and SES correlated with nutrient intake among selected adolescent
      boys.

PMID- 25948466
TI  - Investigation on the lung function of general population in Ilam, west of Iran,
      as a city exposed to dust storm.
AB  - BACKGROUND: Dust storm is one of the most important natural sources of air
      pollution in the Middle East that has caused a major concern in recent years. The
      aim of this study was to evaluate the respiratory tract function of people living
      in Ilam city (Iran) during dust storm. METHODS: A sample size of 250 people was
      selected and the cluster sampling was randomly used from 13 health centers in
      Ilam city. Pulmonary function test (PFT) was determined via a standard spirometry
      apparatus. Vital capacity (VC), Forced Vital capacity (FVC), FVC in first second
      (FEV1), FEV1/VC, FEV1/FVC, peek expiratory flow (PEF), forced expiratory flow
      (FEF25-75%), forced expiratory flow (FEF25-75%), forced expiratory flow (FEF75
      85%), forced mid flow time (FMFT) and maximum voluntary ventilation (MVV) were
      measured. RESULTS: Mean values of respiratory capacities measured in all
      participants excluding FEV1/VC and FMFT were less than predicted mean values by
      ECCS reference. 21.6% of the population suffered from obstructive lesions. This
      value among males (24.1%) was more than females (19.6%). This could be related to
      more exposure (outdoor jobs) of males with dust storms. CONCLUSION: The results
      also showed a negative significant relationship between duration of inhabitance
      in Ilam city and all respiratory capacities. Further studies are needed for
      confident confirmation of whether reduction of respiratory capacities among
      Ilamian people is only related to dust storms.

PMID- 25948467
TI  - The relationship between personality styles of sociotropy and autonomy and
      suicidal tendency in medical students.
AB  - The research aim was investigating the relationship between personality styles of
      autonomy and sociotropy, and suicidal behavior at Zahedan University of medical
      sciences' medical students. This was a descriptive correlational study. The
      population consisted of all medical students at Zahedan University of Medical
      Sciences internship period 2002-2003. The number of samples was 102 patients,
      including 47 males and 55 females. To collect information, the personal style
      inventory (PSI) with 48 items. Twenty four items to assess sociotropy, 24 items
      to assess autonomy, and to measure suicide the suicidal subscale (MMPI) with 21
      items were used. The two scales had the content validity and for the reliability
      used Cronbach a. So the reliability of the personality styles is 0.84 and the
      reliability of the suicidal subscales is 0.83. Data were analyzed using Pearson's
      correlation methods. The results showed that there is an inverse and significant
      relation between autonomic style and trends of suicide in men (P = 0.02, r = 
      0.43), but no association between sociotropy and suicidal tendencies were
      observed in men. There was no significant relationship between autonomy and
      sociotropy personality styles and tendency towards suicide in women. 

PMID- 25948468
TI  - The analysis of cumulative influence of factors of environment on a state of
      health of the population of Vladimir region.
AB  - There was investigated the contribution of factors of environment to formation of
      health for adult population on indicators of mid-annual rates of growth/decrease
      of disease of system of blood circulation and of some interfaced nosology on an
      example of the population of Vladimir region. The differential criterion of
      primary disease of system of blood circulation is considered as an indicator,
      integrally reflecting degree of adaptation to environment conditions on
      population and suitable for construction short-term prognostic estimations. It is
      shown that business factors or the factors of a standard of living characterized
      by economic indicators, are leading risk factors in disease of system of blood
      circulation in Vladimir region which contribution is estimated by size of 38%.
      With use of regressive equations were received look-ahead estimations of annual
      rates of primary disease of system of blood circulation. In the regional centre
      Vladimir was observed more intense situation on rates of disease of system of
      blood circulation, than in Vladimir region. 

PMID- 25948469
TI  - Acceptance of disability: determinants of overcoming social frustration.
AB  - The article is devoted to the subjective reaction of patients at different stages
      of disabling disease, in the context of the formation of a specific cognitive
      emotional and motivational model of "internal picture of disability", depending
      on the severity of social frustration as the most important deconditioning
      factor. We wanted to identify psychological determinant of the specificity of
      adaptive activity of the patient to the situation disabling disease, depending on
      the level of increase social frustration. Nature of adaptation to the disabling
      disease depending on the level of increase social frustration expressed by: 1)
      decrease in self-esteem of patient self-efficacy with an increase in subjective
      experience of disability; 2) the growing tension of personal protective
      mechanisms; 3) reductions coping competence, which, depending on the rise of
      frustration, becomes effective instead of the rational-intelligent, more
      maladaptive emotional. 

PMID- 25948470
TI  - Expression of interleukin-8, interleukin-10 and Epstein-Barr viral-load as
      prognostic indicator in nasopharyngeal carcinoma.
AB  - Interleukin-8 (IL-8) is angiogeneic chemokine that plays a potential role in both
      development and progression of many human malignancies including nasopharyngeal
      carcinoma (NPC). Epstein- Barr virus (EBV) is recognized to be an important
      etiologic agent of NPC as the viral gene products are frequently detected in NPC
      tissue along with the elevation of antibody titre to the viral protein (VCA-p18+
      EBNA1) of IgA in the majority of patients. Elevated plasma of Viral Load is
      regarded as an important marker for the presence of the disease and for the
      monitoring of disease progression. However, other serum /plasma parameters such
      as the level of certain interleukins (IL-8 and IL-10) has also been implicated in
      NPC progression. The study aimed to investigate the correlations between plasma
      Viral Load and the level of interleukin (IL-8) and Interleukin (IL-10) in
      relating these parameters to the stages of NPC. In addition of Viral Load (VCA
      p18+EBNA1) IgA, Interleukin-8 and Interleukin-10 before and after therapy will be
      investigated to seek the possible marker for disease progression. A total of 39
      NPC patients and 29 healthy control individuals enrolled in this study. Plasma
      Viral Load was quantified using real-time quantitative PCR. The Level of plasma
      interleukins both IL-8 and IL-10 were analyzed using ELISA methods. Results
      indicated there was a significant decrease in viral load was detected in plasma
      of NPC patients following therapy. Plasma of viral load was shown to be a good
      prognosticator for disease progression. There were positive correlation between
      plasma of viral load and IL-8. These non invasive parameters expressed in blood,
      could be substitutes of viral load using brushing method, which is invasive. In
      conclusion that: Viral Load, (VCA-p18+EBNA1) IgA and IL-8 levels are promising
      markers for the presence of NPC and progression of the disease. 

PMID- 25948471
TI  - The effect of valeric on anxiety severity in women undergoing
      hysterosalpingography.
AB  - AIM & SCOPE: Hysterosalpingography (HSG) is the radiographic evaluation of the
      uterine cavity and fallopian tubes, which is generally assumed as a stressful and
      painful procedure. This study aims to determine effect of oral Valeric capsules
      on anxiety severity in women under Hysterosalpingography. METHOD & EXAMINATION:
      This study, as a double-blind clinical trial, was conducted on 64 infertile women
      undergoing hysterosalpingography, who referred to radiology ward at Comprehensive
      Women's hospital. To measure anxiety, visual analog anxiety scale was used 90
      minutes before starting procedure, individuals in intervention group (n=32)
      received a single dose (1,500 mg) of 3 Valeric capsules, together with routine
      prophylaxy, where routine prophylaxis contains Mefenamic acid 250mg capsules in
      30 minutes before procedure, and the same capsules were prescribed to placebo
      group (n=32) with the same instruction. Anxiety severity before and once 90
      minutes after intervention in both groups were measured and compared. RESULTS:
      There was no difference on anxiety severity before intervention in both groups
      (p=0.26), and the groups were homogeneous; after intervention, a significant
      difference on anxiety severity was reported in both groups (p<0/0001), and
      anxiety score in intervention group compared to placebo reduced statistically.
      CONCLUSION: Present study indicated that Valeric was effective on reducing
      anxiety in women undergoing hysterosalpingography.

PMID- 25948472
TI  - Effect of the CYP2D6 gene polymorphism on postoperative analgesia of tramadol in
      Han nationality nephrectomy patients.
AB  - OBJECTIVE: Tramadol is a synthetic opioid which has analgesic efficacy in the
      postoperative pain. It is metabolized by polymorphic enzyme cytochrome P450
      (CYP2D6). Patients with different CYP2D6 genotypes would have different responses
      to tramadol in pain relief. The CYP2D6*10 allele is the most common allele in a
      Chinese population. The aim of this study was to evaluate whether the different
      CYP2D6*10 genotypes have an effect on the postoperative tramadol analgesia in the
      Chinese population after elective nephrectomy. METHODS: One hundred and twenty
      patients after performed elective nephrectomy were enrolled in this study after
      being approved by the local Ethics Committee. The patients were given patient
      controlled analgesia (PCA) which included 10 mg/ml tramadol after receiving a
      loading dose of 100 mg tramadol and 1 mg granisetron intravenously. Blood samples
      were collected after induction of anesthesia. The CYP2D6*10 polymorphism was
      analyzed by polymerase chain reaction restriction fragment length polymorphism
      (PCR-RFLP). According to the results, the patients were divided into three groups
      (CYP2D6*1/*1, n = 33; CYP2D6*1/*10, n = 28; CYP2D6*10/*10, n = 50). The total
      consumption of tramadol, visual analogue scale (VAS) score, and PCA control times
      among the three genotype groups for 2, 4, 24, 48, and 72 h after operation were
      compared. RESULTS: Nine out of 120 patients were dropped out of the study; 111
      patients completed the study. The frequency of CYP2D6*10 allele was 57.7%. The
      demographic data among the three groups were comparable. The consumption of
      tramadol, patient self-control times of pump, and VAS score in CYP2D6*10/*10
      group were significantly higher than that in CYP2D6*1/*1 or CYP2D6*1/*10 group at
      2 and 4 h (P < 0.05), while it did not differ between CYP2D6*1/*1 and
      CYP2D6*1/*10 group (P > 0.05). There was no difference in the incidence of nausea
      and vomiting among the three groups (P > 0.05). No sever apnea was recorded in
      these groups. CONCLUSIONS: Different CYP2D6*10 genotypes have an influence on the
      analgesic effect of tramadol in Han nationality patients after elective
      nephrectomy.

PMID- 25948473
TI  - Three conserved MyD88-recruiting TLR residues exert different effects on the
      human TLR4 signaling pathway.
AB  - Stimulation of Toll-like receptor (TLR) 4 leads to the activation of both MyD88
      dependent and MyD88-independent pathways through the recruitment of adaptors
      TIRAP/MyD88 and TRIF/TRAM, respectively. However, the molecular basis of the TLR4
      Toll/interleukin-1 receptor (TIR) domain in recruiting these downstream adaptors
      is still not entirely clear. Here, we identify three amino acid residues (714P in
      the BB loop, 696L in the alphaA helix and 721N in the alphaB sheet) conserved in
      all MyD88-recruited TLRs, but not the TLR3 TIR domain, as being critical for TLR4
      responsiveness to LPS. These results were based on the substitution of each
      residue with a residue of the opposite type (hydrophilic/hydrophobic). However,
      the responsiveness of the TLR4 mutants to LPS was only partially decreased when
      each residue was replaced with a residue having the same
      hydrophilicity/hydrophobicity. This result is likely associated with an
      alteration in the BB-loop conformation of each TLR4 mutant and its ability to
      recruit the downstream adaptor TRAM. Thus, we identified three amino acids
      essential for TLR4 signaling, and their replacement with a residue of the same or
      opposite hydrophilicity/hydrophobicity greatly affected TLR4 signaling. This
      study furthers our understanding of the molecular mechanism by which the TLR4 TIR
      domain modulates TLR4 signaling and also provides new insight for the design of
      antisepsis therapy.

PMID- 25948474
TI  - Enhanced expression of trim14 gene suppressed Sindbis virus reproduction and
      modulated the transcription of a large number of genes of innate immunity.
AB  - In the present research, we have studied an influence of enhanced expression
      TRIM14 on alphavirus Sindbis (SINV, Togaviridae family) infection. In the HEK293
      cells transfected with human trim14 gene (HEK-trim14), SINV yield after infection
      was decreased 1000-10,000 times (3-4 lg of TCD50/ml) at 24 h p.i. and
      considerably less (1-2 lg of TCD50/ml) at 48 h p.i. Analysis of the expression of
      43 genes directly or indirectly involved in innate immune machine in HEK-trim14
      non-infected cells comparing with the control (non-transfected) HEK293 cells
      revealed that stable trim14 transfection in HEK293 cells caused increased
      transcription of 18 genes (ifna, il6 (ifnbeta2), isg15, raf-1, NF-kB (nf-kb1,
      rela, nf-kb2, relb), grb2, grb3-3, traf3ip2, junB, c-myb, pu.1, akt1, tyk2, erk2,
      mek2) and lowered transcription of 3 genes (ifngamma, gata1, il-17a). The similar
      patterns of genes expression observe in SINV-infected non-transfected HEK293
      cells. However, SINV infection of HEK-trim14 cells caused inhibition of the most
      interferon cascade genes as well as subunits of transcription factor NF-kappaB.
      Thus, stable enhanced expression of trim14 gene in cells activates the
      transcription of many immunity genes and suppresses the SINV reproduction, but
      SINV infection of HEK-trim14 cells promotes inhibition of some genes involved in
      innate immune system.

PMID- 25948476
TI  - Erratum to: History of narcolepsy at Stanford University.

PMID- 25948475
TI  - T regulatory cells: Achilles' heel of Mycobacterium tuberculosis infection?
AB  - T regulatory cells (Treg) constitute a specialized subset of T cells that play a
      pivotal role in preventing the occurrence of autoimmune diseases by suppressing
      deleterious activities of immune cells. Contrarily, they can have adverse effect
      on immune response against infectious diseases where Treg weaken the host
      immunity leading to enhanced microbial load and thereby increase in severity of
      the disease. Here, we have attempted to review plethora of information
      documenting prevalence of Treg in tuberculosis (TB) and their involvement in
      progression and immunopathogenesis of the disease. Further, we have laid emphasis
      on the possible use of Treg as a biomarker for determining the TB treatment
      efficacy. Also, we have discussed the probable contribution of Treg in dampening
      the efficacy of BCG, the anti-TB vaccine. Finally, we have speculated some of the
      possible strategies which might be explored by exploiting Treg for enhancing the
      efficacy of TB management. 

PMID- 25948477
TI  - Molecular network-based analysis of guizhi-shaoyao-zhimu decoction, a TCM herbal
      formula, for treatment of diabetic peripheral neuropathy.
AB  - AIM: Guizhi-shaoyao-zhimu decoction (GSZ), a traditional Chinese medicine (TCM)
      herbal formula, has been shown effective in the treatment of diabetic peripheral
      neuropathy (DPN). In this study, network analysis was performed to decipher the
      molecular mechanisms of GSZ in the treatment of DPN. METHODS: The chemical
      components of the 3 herbs forming GSZ, ie, Ramulus Cinnamomi (Guizhi), Paeonia
      lactiflora (Shaoyao) and Rhizoma Anemarrhenae (Zhimu), were searched in Chinese
      medicine dictionaries, and their target proteins were identified in PubChem. DPN
      genes were searched in PubMed gene databases. Ingenuity Pathway Analysis (IPA)
      was used to build the GSZ pharmacological network and DPN molecular network. The
      canonical pathways between the two networks were compared to decipher the
      molecular mechanisms of GSZ in the treatment of DPN. RESULTS: Sixty-one protein
      targets for Guizhi, 31 targets for Shaoyao, 47 targets for Zhimu, as well as 23
      genes related to DPN were identified and uploaded to IPA. The primary functions
      of the DPN molecular network were inflammatory response, metabolic disease,
      cellular assembly and organization. As far as the pharmacological network
      functions were concerned, Guizhi target proteins were involved in neurological
      disease, inflammatory disease, cellular growth and proliferation, cell signaling,
      molecular transport, and nucleic acid metabolism, Shaoyao target proteins were
      related to neurological disease, inflammatory disease, and Zhimu target proteins
      focused on cell death and survival, cellular movement, immune cell trafficking,
      DNA replication, recombination and repair, and cell cycle. In the three-herb
      combination GSZ, several new network functions were revealed, including the
      inflammatory response, gene expression, connective tissue development and
      function, endocrine system disorders, and metabolic disease. The canonical
      pathway comparison showed that Shaoyao focused on IL-12 signaling and production
      in macrophages, and Zhimu focused on TNFR2 signaling, death receptor signaling,
      ILK signaling, IL-17A in gastric cells, IL-6 signaling, IL-8 signaling, the role
      of JAK1, JAK2, and TYK2 in interferon signaling, IL-9 signaling, HMGB1 signaling,
      NO production and ROS production in macrophages, whereas GSZ focused aryl
      hydrocarbon receptor signaling and apoptosis signaling in addition to those
      pathways induced by Guizhi, Shaoyao and Zhimu. CONCLUSION: Although each single
      herb can affect some DPN-related functions and pathways, GSZ exerts more effects
      on DPN-related functions and pathways. The effects of GSZ on aryl hydrocarbon
      receptor signaling and apoptosis signaling pathways may be the key components of
      its total molecular mechanisms.

PMID- 25948478
TI  - Identification and in vitro pharmacological characterization of a novel and
      selective alpha7 nicotinic acetylcholine receptor agonist, Br-IQ17B.
AB  - AIM: Alpha7-nicotinic acetylcholine receptor (alpha7 nAChR) is a ligand-gated
      Ca(2+)-permeable ion channel implicated in cognition and neuropsychiatric
      disorders. Activation of alpha7 nAChR improves learning, memory, and sensory
      gating in animal models. To identify novel alpha7 nAChR agonists, we synthesized
      a series of small molecules and characterized a representative compound, Br
      IQ17B, N-[(3R)-1-azabicyclo[2,2,2]oct-3-yl]-5-bromoindolizine-2-carboxamide,
      which specifically activates alpha7 nAChR. METHODS: Two-electrode voltage clamp
      (TEVC) recordings were primarily used for screening in Xenopus oocytes expressing
      human alpha7 nAChR. Assays, including radioisotope ligand binding, Western blots,
      whole-cell recordings of hippocampal culture neurons, and spontaneous IPSC
      recordings of brain slices, were also utilized to evaluate and confirm the
      specific activation of alpha7 nAChR by Br-IQ17B. RESULTS: Br-IQ17B potently
      activates alpha7 nAChR with an EC50 of 1.8+/-0.2 MUmol/L. Br-IQ17B is selective
      over other subtypes such as alpha4beta2 and alpha3beta4, but it blocks 5-HT3A
      receptors. Br-IQ17B displaced binding of the alpha7 blocker [(3)H]-MLA to
      hippocampal crude membranes with a Ki of 14.9+/-3.2 nmol/L. In hippocampal
      neurons, Br-IQ17B evoked alpha7-like currents that were inhibited by MLA and
      enhanced in the presence of the alpha7 PAM PNU-120596. In brain slice recordings,
      Br-IQ17B enhanced GABAergic synaptic transmission in CA1 neurons.
      Mechanistically, Br-IQ17B increased ERK1/2 phosphorylation that was MLA
      sensitive. CONCLUSION: We identified the novel, potent, and selective alpha7
      agonist Br-IQ17B, which enhances synaptic transmission. Br-IQ17B may be a helpful
      tool to understand new aspects of alpha7 nAChR function, and it also has
      potential for being developed as therapy for schizophrenia and cognitive
      deficits.

PMID- 25948479
TI  - Telerehab III: a multi-center randomized, controlled trial investigating the long
      term effectiveness of a comprehensive cardiac telerehabilitation program-
      rationale and study design.
AB  - BACKGROUND: Telerehabilitation has been proposed as an adjunct/alternative to
      standard center-based cardiac rehabilitation. Two recent systematic reviews
      showed non-inferiority and/or superiority of this remote approach for cardiac
      rehabilitation. However, these trials focused only on one core component of
      cardiac rehabilitation and telemonitoring, rather than implementing a more
      comprehensive approach. The aim of Telerehab III is to investigate the long-term
      effectiveness of the addition of a patient-tailored, internet-based
      telerehabilitation program implementing multiple cardiac rehabilitation core
      components and using both telemonitoring and telecoaching strategies to standard
      cardiac rehabilitation. METHODS/DESIGN: In this prospective, multi-center
      randomized, controlled trial 140 patients with coronary artery disease and/or
      chronic heart failure patients will be recruited between February 2013 and
      February 2015. Patients will be randomized 1:1 to an intervention group
      (receiving an internet-based telerehabilitation program in addition to standard
      cardiac rehabilitation) or to standard cardiac rehabilitation alone. The mean
      follow-up is at least 6 months. The primary endpoint is peak oxygen consumption
      (VO2 peak). Secondary endpoints include measured and self-reported daily physical
      activity, cardiovascular risk factor control, health-related quality of life,
      days lost due to (non)cardiovascular rehospitalizations and time to first
      (non)cardiovascular rehospitalization. A clinical event committee blinded to
      treatment allocation assesses causes of rehospitalizations. DISCUSSION: Telerehab
      III will be one of the first studies to examine the added value of a more
      comprehensive cardiac telerehabilitation program, focusing on multiple cardiac
      rehabilitation core components. It has the potential to augment current standard
      center-based cardiac rehabilitation practices and to be used as a model for other
      disease prevention programs. TRIAL REGISTRATION: Current controlled trials
      ISRCTN29243064. Registration date 21 January 2015.

PMID- 25948481
TI  - Vitrified sheep isolated secondary follicles are able to grow and form antrum
      after a short period of in vitro culture.
AB  - The risk of reintroducing malignant cells after ovarian graft into patients
      following post-cancer treatment is an obstacle for clinical applications
      (autotransplantation). In this context, in vitro follicle culture would be an
      alternative to transplantation in order to minimize such risks. Therefore, the
      aim of this study was to compare the development of secondary follicles after
      vitrification in isolated form (without stroma) with vitrification in in situ
      form (within fragments of ovarian tissue). Follicles were first isolated from
      ovarian fragments from mixed-breed ewes and then vitrified; these comprised the
      Follicle-Vitrification group (Follicle-Vit), or fragments of ovarian tissue were
      first vitrified, followed by isolation of the follicles, resulting in the Tissue
      Vitrification group (Tissue-Vit). Control and vitrified groups were submitted to
      in vitro culture (6 days) and follicular morphology, viability, antrum formation,
      follicle and oocyte diameter, growth rate, ultrastructural characteristics and
      cell proliferation were evaluated. The percentages of morphologically normal
      follicles and antrum formation were similar among groups. Follicular viability
      and oocyte diameter were similar between Follicle-Vit and Tissue-Vit. The
      follicular diameter and growth rate of Follicle-Vit were similar to the Control,
      while those of Tissue-Vit were significantly lower compared to the Control. Both
      vitrified groups had an augmented rate of granulosa cellular proliferation
      compared to Control. Secondary follicles can be successfully vitrified before or
      after isolation from the ovarian tissue without impairing their ability to
      survive and grow during in vitro culture. 

PMID- 25948480
TI  - Gene expression profiling of porcine mammary epithelial cells after challenge
      with Escherichia coli and Staphylococcus aureus in vitro.
AB  - Postpartum Dysgalactia Syndrome (PDS) represents a considerable health problem of
      postpartum sows, primarily indicated by mastitis and lactation failure. The
      poorly understood etiology of this multifactorial disease necessitates the use of
      the porcine mammary epithelial cell (PMEC) model to identify how and to what
      extent molecular pathogen defense mechanisms prevent bacterial infections at the
      first cellular barrier of the gland. PMEC were isolated from three lactating sows
      and challenged with heat-inactivated potential mastitis-causing pathogens
      Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) for 3 h and 24
      h, in vitro. We focused on differential gene expression patterns of PMEC after
      pathogen challenge in comparison with the untreated control by performing
      microarray analysis. Our results show that a core innate immune response of PMEC
      is partly shared by E. coli and S. aureus. But E. coli infection induces much
      faster and stronger inflammatory response than S. aureus infection. An immediate
      and strong up-regulation of genes encoding cytokines (IL1A and IL8), chemokines
      (CCL2, CXCL1, CXCL2, CXCL3, and CXCL6) and cell adhesion molecules (VCAM1, ICAM1,
      and ITGB3) was explicitly obvious post-challenge with E. coli inducing a rapid
      recruitment and activation of cells of host defense mediated by IL1B and TNF
      signaling. In contrast, S. aureus infection rather induces the expression of
      genes encoding monooxygenases (CYP1A1, CYP3A4, and CYP1B1) initiating processes
      of detoxification and pathogen elimination. The results indicate that the course
      of PDS depends on the host recognition of different structural and pathogenic
      profiles first, which critically determines the extent and effectiveness of
      cellular immune defense after infection. 

PMID- 25948482
TI  - Feasibility of human hair follicle-derived mesenchymal stem cells/CultiSpher((r))
      G constructs in regenerative medicine.
AB  - The use of human mesenchymal stem cells (hMSCs) in cell therapies has increased
      the demand for strategies that allow efficient cell scale-up. Preliminary data on
      the three-dimensional (3D) spinner culture describing the potential use of
      microcarriers for hMSCs culture scale-up have been reported. We exploited a rich
      source of autologous stem cells (human hair follicle) and demonstrated the robust
      in vitro long-term expansion of human hair follicle-derived mesenchymal stem
      cells (hHF-MSCs) by using CultiSpher((r))-G microcarriers. We analyzed the
      feasibility of 3D culture by using hHF-MSCs/CultiSpher((r))-G microcarrier
      constructs for its potential applicability in regenerative medicine by
      comparatively analyzing the performance of hHF-MSCs adhered to the
      CultiSpher((r))-G microspheres in 3D spinner culture and those grown on the
      gelatin-coated plastic dishes (2D culture), using various assays. We showed that
      the hHF-MSCs seeded at various densities quickly adhered to and proliferated well
      on the microspheres, thus generating at least hundreds of millions of hHF-MSCs on
      1 g of CultiSpher((r))-G within 12 days. This resulted in a cumulative cell
      expansion of greater than 26-fold. Notably, the maximum and average proliferation
      rates in 3D culture were significantly greater than that of the 2D culture.
      However, the hHF-MSCs from both the cultures retained surface marker and nestin
      expression, proliferation capacity and differentiation potentials toward
      adipocytes, osteoblasts and smooth muscle cells and showed no significant
      differences as evidenced by Edu incorporation, cell cycle, colony formation,
      apoptosis, biochemical quantification and qPCR assays. 

PMID- 25948483
TI  - Origin of IgM(+)IgG(+) lymphocytes in the bursa of Fabricius.
AB  - IgM(+)IgG(+) B cells were detected, by immunofluorescence staining of single
      cells, in the bursa of Fabricius after hatching. To study the role of maternal
      IgG (MIgG) in this emergence of IgM(+)IgG(+) B cells, MIgG-free chicks were
      established from surgically bursectomized hens. Deprivation of MIgG in chicks
      completely prevented the appearance of IgM(+)IgG(+) B cells in the bursa 1 week
      after hatching. However, introduction of fluorescein-isothiocyanate-labeled MIgG
      to MIgG-free chick embryos on day 18 of incubation retrieved IgM(+)IgG(+) B cells
      in the bursa 1 week after hatching. Thus, IgM(+)IgG(+) B cells are induced by the
      binding of MIgG to IgM(+) B cells in the bursa after hatching. Nevertheless, no
      binding of MIgG to IgM(+) B cells was observed in the bursa of chick embryos in
      which B-cell proliferation and differentiation were independent of external
      antigens (Ags). Additionally, the binding of MIgG to IgM(+) B cells after
      hatching was prevented by the isolation of the bursa from environmental stimuli
      by bursal duct ligation. Therefore, Ag stimulation from the external environment
      to the bursa is indispensable for the binding of MIgG to IgM(+) B cells in the
      bursa. Taken together, the data demonstrate that IgM(+)IgG(+) B cells are
      generated by Ag-dependent binding of MIgG to IgM(+) B cells in the bursa after
      hatching. 

PMID- 25948486
TI  - Errata. Adult hemolytic uremic syndrome associated with Streptococcus pneumoniae.

PMID- 25948484
TI  - Characterization of matrix metalloproteinase-2 and -9, ADAM-10 and N-cadherin
      expression in human glioblastoma multiforme.
AB  - Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary
      brain tumor in humans, whose invasiveness and proliferation are associated with
      poor prognosis. Matrix metalloproteinases (MMPs) and the related family of "a
      disintegrin and metalloproteinase" (ADAM) both contribute to increase cell
      invasion, and its substrate N-cadherin is involved in proliferation and
      metastatic capacities of tumor cells. However, these molecular determinants of
      aggressiveness have not been adequately characterized in GBM. In an attempt to
      better define these pathogenetic signatures, in the present study we evaluated
      the comparative expression of two main MMPs (MMP-2 and -9), as well as of ADAM-10
      and N-cadherin in surgical samples from patients diagnosed with WHO grade IV GBM
      (n = 25) and in cortical tissue specimens obtained from untreatable epileptic
      patients (controls, n = 8) through a series of histopathological,
      immunohistochemical and biochemical tests. Our studies revealed that both MMP-2
      and -9 immunoreactivities (IRs) were upregulated in 13 of 25 (52 %) and 19 of 25
      (76 %) GBMs, respectively, and the extent of the increase was highly significant
      with respect to controls (p < 0.001). ADAM-10 IR was also found to be increased
      (p < 0.001) in 16 of 25 GBM specimens (64 %). Conversely, N-cadherin IR was
      remarkably decreased (p < 0.001) in almost the totality of tumor samples (22 of
      25, 88 %). A similar trend was also obtained at the mRNA and protein level by
      qPCR and western blot analyses, respectively. Collectively, the current study
      provides a comprehensive molecular portrayal of some of the major pathological
      hallmarks of GBM aggressiveness, which could be exploitable as potential targets
      for a new therapeutic approach. 

PMID- 25948487
TI  - Hemophilia care in China: review of care for 417 hemophilia patients from 11
      treatment centers in Shanxi Province.
AB  - AIMS: We analyzed the clinical features of 417 patients with hemophilia from 11
      Hemophilia Treatment Centers in Shanxi Province (SP) in China. METHODS: We used
      data collected in the national registry of hemophilia A and hemophilia B in SP
      from January 2010 to December 2013. RESULTS: Ratio of hemophilia A:hemophilia B
      patients was 5:1, of which 48% (200/417) were severe, 31% (129/417) moderate and
      21% (88/417) mild. Episodes of joint bleeding occurred in 73% (305/417) of
      patients. Only 4% (15/417) of patients received tertiary prophylaxis. Three
      percent of patients (2/72) were hepatitis B virus-Ab positive, and 7% (5/72) of
      patients were hepatitis C virus-Ab positive. The incidence of inhibitors was 6%
      (11/182). CONCLUSION: The ability to manage hemophilia in SP remains suboptimal.
      However, due to limited data, the evaluation and extrapolation of large
      hemophilia populations in SP are restricted, therefore, further studies with a
      large cohort are needed.

PMID- 25948489
TI  - Going above and beyond for implementation: the development and validity testing
      of the Implementation Citizenship Behavior Scale (ICBS).
AB  - BACKGROUND: In line with recent research on the role of the inner context of
      organizations in implementation effectiveness, this study extends research on
      organizational citizenship behavior (OCB) to the domain of evidence-based
      practice (EBP) implementation. OCB encompasses those behaviors that go beyond
      what is required for a given job that contribute to greater organizational
      effectiveness. The goal of this study was to develop and test a measure of
      implementation citizenship behavior (ICB) or those behaviors that employees
      perform that go above and beyond what is required in order to support EBP
      implementation. METHODS: The primary participants were 68 supervisors from ten
      mental health agencies throughout California. Items measuring ICB were developed
      based on past research on OCB and in consultation with experts on EBP
      implementation in mental health settings. Supervisors rated 357 of their
      subordinates on ICB and implementation success. In addition, 292 of the
      subordinates provided data on self-rated performance, attitudes towards EBPs,
      work experience, and full-time status. The supervisor sample was randomly split,
      with half used for exploratory factor analyses and the other half for
      confirmatory factor analyses. The entire sample of supervisors and subordinates
      was utilized for analyses assessing the reliability and construct validity of the
      measure. RESULTS: Exploratory factor analyses supported the proposed two-factor
      structure of the Implementation Citizenship Behavior Scale (ICBS): (1) Helping
      Others and (2) Keeping Informed. Confirmatory factor analyses with the other half
      of the sample supported the factor structure. Additional analyses supported the
      reliability and construct validity for the ICBS. CONCLUSIONS: The ICBS is a
      pragmatic brief measure (six items) that captures critical behaviors employees
      perform to go above and beyond the call of duty to support EBP implementation,
      including helping their fellow employees on implementation-related activities and
      keeping informed about issues related to EBP and implementation efforts. The ICBS
      can be used by researchers to better understand the outcomes of improved
      organizational support for implementation (i.e., implementation climate) and the
      proximal predictors of implementation effectiveness. The ICBS can also provide
      insight for organizations, practitioners, and managers by focusing on key
      employee behaviors that should increase the probability of implementation
      success.

PMID- 25948490
TI  - Assessment of chest pain in a low risk patient: is the exercise tolerance test
      obsolete?

PMID- 25948488
TI  - Fibroblast growth factor-2 regulates human cardiac myofibroblast-mediated
      extracellular matrix remodeling.
AB  - BACKGROUND: Tissue fibrosis and chamber remodeling is a hallmark of the failing
      heart and the final common pathway for heart failure of diverse etiologies.
      Sustained elevation of pro-fibrotic cytokine transforming growth factor-beta1
      (TGFbeta1) induces cardiac myofibroblast-mediated fibrosis and progressive
      structural tissue remodeling. OBJECTIVES: We examined the effects of low
      molecular weight fibroblast growth factor (LMW-FGF-2) on human cardiac
      myofibroblast-mediated extracellular matrix (ECM) dysregulation and remodeling.
      METHODS: Human cardiac biopsies were obtained during open-heart surgery and
      myofibroblasts were isolated, passaged, and seeded within type I collagen
      matrices. To induce myofibroblast activation and ECM remodeling, myofibroblast
      seeded collagen gels were exposed to TGFbeta1. The extent of ECM contraction,
      myofibroblast activation, ECM dysregulation, and cell apoptosis was determined in
      the presence of LMW-FGF-2 and compared to its absence. Using a novel floating
      nylon-grid supported thin collagen gel culture platform system, myofibroblast
      activation and local ECM remodeling around isolated single cells was imaged using
      confocal microscopy and quantified by image analysis. RESULTS: TGFbeta1 induced
      significant myofibroblast activation and ECM dysregulation as evidenced by
      collagen gel contraction, structural ECM remodeling, collagen synthesis, ECM
      degradation, and altered TIMP expression. LMW-FGF-2 significantly attenuated
      TGFbeta1 induced myofibroblast-mediated ECM remodeling. These observations were
      similar using either ventricular or atrial-derived cardiac myofibroblasts. In
      addition, for the first time using individual cells, LMW-FGF-2 was observed to
      attenuate cardiac myofibroblast activation and prevent local cell-mediated ECM
      perturbations. CONCLUSIONS: LMW-FGF-2 attenuates human cardiac myofibroblast
      mediated ECM remodeling and may prevent progressive maladaptive chamber
      remodeling and tissue fibrosis for patients with diverse structural heart
      diseases.

PMID- 25948492
TI  - Supplemental dose of antithrombin use in disseminated intravascular coagulation
      patients after abdominal sepsis.
AB  - The effectiveness of supplemental dose antithrombin administration (1,500 to
      3,000 IU/ day) for patients with sepsis-associated disseminated intravascular
      coagulation (DIC), especially sepsis due to abdominal origin, remains uncertain.
      This was a retrospective cohort study of patients with mechanically ventilated
      septic shock and DIC after emergency surgery for perforation of the lower
      intestinal tract using a nationwide administrative database, Japanese Diagnosis
      Procedure Combination inpatient database. A total of 2,164 patients treated at
      612 hospitals during the 33-month study period between 2010 and 2013 were divided
      into an antithrombin group (n=1,021) and a control group (n=1,143), from which
      518 propensity score-matched pairs were generated. Although there was no
      significant 28-day mortality difference between the two groups in the unmatched
      groups (control vs antithrombin: 25.7 vs 22.9 %; difference, 2.8 %; 95 %
      confidence interval [CI], -0.8-6.4), a significant difference existed between the
      two groups in propensity-score weighted groups (26.3 vs 21.7 %; difference, 4.6
      %; 95 % CI, 2.0-7.1) and propensity-score matched groups (27.6 vs 19.9 %;
      difference, 7.7 %; 95 % CI, 2.5-12.9). Logistic regression analyses showed a
      significant association between antithrombin use and lower 28-day mortality in
      propensity-matched groups (odds ratio, 0.65; 95 % CI, 0.49-0.87). Analysis using
      the hospital antithrombin-prescribing rate as an instrumental variable showed
      that receipt of antithrombin was associated with a 6.5 % (95 % CI, 0.05-13.0)
      reduction in 28-day mortality. Supplemental dose of antithrombin administration
      may be associated with reduced 28-day mortality in sepsis-associated DIC patients
      after emergency laparotomy for intestinal perforation. 

PMID- 25948491
TI  - Phenotypic Approaches to Identify Inhibitors of B Cell Activation.
AB  - An EPIC label-free phenotypic platform was developed to explore B cell receptor
      (BCR) and CD40R-mediated B cell activation. The phenotypic assay measured the
      association of RL non-Hodgkin's lymphoma B cells expressing lymphocyte function
      associated antigen 1 (LFA-1) to intercellular adhesion molecule 1 (ICAM-1)-coated
      EPIC plates. Anti-IgM (immunoglobulin M) mediated BCR activation elicited a
      response that was blocked by LFA-1/ICAM-1 specific inhibitors and a panel of
      Bruton's tyrosine kinase (BTK) inhibitors. LFA-1/ICAM-1 association was further
      increased on coapplication of anti-IgM and mega CD40L when compared to individual
      application of either. Anti-IgM, mega CD40L, or the combination of both displayed
      distinct kinetic profiles that were inhibited by treatment with a BTK inhibitor.
      We also established a FLIPR-based assay to measure B cell activation in Ramos
      Burkitt's lymphoma B cells and an RL cell line. Anti-IgM-mediated BCR activation
      elicited a robust calcium response that was inhibited by a panel of BTK
      inhibitors. Conversely, CD40R activation did not elicit a calcium response in the
      FLIPR assay. Compared to the FLIPR, the EPIC assay has the propensity to identify
      inhibitors of both BCR and CD40R-mediated B cell activation and may provide more
      pharmacological depth or novel mechanisms of action for inhibition of B cell
      activation. 

PMID- 25948493
TI  - Should Health Numeracy Be Assessed Objectively or Subjectively?
AB  - INTRODUCTION: Because current evidence suggests that numeracy affects how people
      make decisions, it is an important factor to account for in studies assessing the
      effectiveness of medical decision support interventions. Subjective and objective
      numeracy assessment methods are available that vary in theoretical background,
      skills assessed, known relationship with decision making skills, and ease of
      implementation. The best way to use these tools to assess numeracy when
      conducting medical decision-making research is currently unknown. METHODS: We
      conducted Internet surveys comparing numeracy assessments obtained using the
      subjective numeracy scale (SNS) and 5 objective numeracy scales. Each study
      participant completed the SNS and 1 objective numeracy measure. Following each
      assessment, participants indicated willingness to repeat the assessment and rated
      its user acceptability. RESULTS: The overall response rate was 78%, resulting in
      a total sample size of 673. Spearman correlations between the SNS and the
      objective numeracy measures ranged from 0.19 to 0.44. Acceptability assessments
      for the short form of the Numeracy Understanding in Medicine Instrument and the
      SNS did not differ significantly. The other objective scales all had lower
      acceptability ratings than the SNS. CONCLUSIONS: These findings are consistent
      with prior research suggesting that objective and subjective numeracy scales
      measure related but distinct constructs. Due to current uncertainty regarding
      which construct is more likely to influence the effectiveness of decision support
      interventions, these findings warrant further investigation to determine the
      proper use of objective versus subjective numeracy assessments in medical
      decision-making research. Pending additional information, a reasonable approach
      is to measure both objective and subjective numeracy so that the full range of
      actual and perceived numeracy skills can be taken into account.

PMID- 25948494
TI  - Plasma membrane proteomic analysis of human Gastric Cancer tissues: revealing
      flotillin 1 as a marker for Gastric Cancer.
AB  - BACKGROUND: Gastric cancer remains the second leading cause of cancer-related
      deaths in the world. Successful early gastric cancer detection is hampered by
      lack of highly sensitive and specific biomarkers. Plasma membrane proteins
      participate and/or have a central role in the metastatic process of cancer cells
      and are potentially useful for cancer therapy due to easy accessibility of the
      targets. METHODS: In the present research, TMT method followed by mass
      spectrometry analysis was used to compare the relative expression levels of
      plasma membrane proteins between noncancer and gastric cancer tissues. RESULTS:
      Of a total data set that included 501 identified proteins, about 35% of the
      identified proteins were found to be plasma membrane and associated proteins.
      Among them, 82 proteins were at least 1.5-fold up- or down-regulated in gastric
      cancer compared with the adherent normal tissues. CONCLUSIONS: A number of
      markers (e.g. annexin A6, caveolin 1, epidermal growth factor receptor, integrin
      beta 4) were previously reported as biomarkers of GC. Additionally, several
      potential biomarkers participated in endocytosis pathway and integrin signaling
      pathways were firstly identified as differentially expressed proteins in GC
      samples. Our findings also supported the notion that flotillin 1 is a potential
      biomarker that could be exploited for molecular imaging-based detection of
      gastric cancer. Together, the results show that subcellular proteomics of tumor
      tissue is a feasible and promising avenue for exploring oncogenesis.

PMID- 25948495
TI  - Paralympics and conversion disorder.

PMID- 25948496
TI  - The impact of the Italian guidelines on antibiotic prescription practices for
      acute otitis media in a paediatric emergency setting.
AB  - BACKGROUND: Acute otitis media (AOM) is one of the most common childhood
      infectious diseases. The recent Italian Pediatric Guidelines for the treatment of
      AOM constitutes a step forward in the management of children with uncomplicated
      AOM. The aim of this study was to evaluate antibiotic prescription patterns for
      AOM in a Pediatric Emergency Department (PED) after those guidelines were
      introduced and to assess the relationship between implementation of the "watchful
      waiting" strategy and the incidence of acute mastoiditis in the PED. METHODS:
      This retrospective study was conducted between 1st January 2007 to 31st December
      2013 at the PED of the University of Modena and Reggio Emilia in Modena (Italy).
      All children between 0 and 14 years who were examined because of symptoms and/or
      signs of AOM and acute mastoiditis were enrolled. Pearson's chi-squared test was
      used to evaluate if introduction of the Italian Paediatric Guidelines was
      associated with a reduction in the antibiotic prescription pattern in children
      with AOM and/or with an increase in mastoiditis frequency. RESULTS: 4,573 (89.4%)
      patients were included in our analysis, antibiotics were prescribed to 81% cases
      of the children diagnosed with AOM. The frequency of antibiotic prescribing
      continued to be stable after the Italian guidelines were introduced (82% versus
      81%). Forty children were admitted to hospital with a diagnosis of acute
      mastoiditis. Our study did not find any association between the number of cases
      of acute mastoiditis and the percentage of patients treated with antibiotics; the
      annual incidence of mastoiditis before and after the new guidelines were
      published was, in fact, stable. CONCLUSIONS: Despite the diffusion of clinical
      guidelines recommending a "watchful waiting" approach for children with AOM, the
      antibiotic prescription rate continues to be high. It appears to be more
      difficult to impact the percentage of cases for which antibiotics are prescribed
      than the type of antibiotic that is utilized. In view of these findings, a close
      follow-up control by the primary care paediatrician or a scheduled follow-up
      appointment at the PED and incisive campaigns to promote parents' awareness of
      proper antibiotic use appear to be warranted.

PMID- 25948497
TI  - Diabetes self-management interventions for adults with type 2 diabetes living in
      rural areas: a systematic literature review.
AB  - In rural communities, high rates of diabetes and its complications are compounded
      by limited access to health care and scarce community resources. We
      systematically reviewed the evidence for the impact of diabetes self-management
      education interventions designed for patients living in rural areas on glycemic
      control and other diabetes outcomes. Fifteen studies met inclusion criteria. Ten
      were randomized controlled trials. Intervention strategies included in-person
      diabetes (n = 9) and telehealth (n = 6) interventions. Four studies demonstrated
      between group differences for biologic outcomes, four studies demonstrated
      changes in behavior, and three studies demonstrated changes in knowledge.
      Intervention dose was associated with improved A1c or weight loss in two studies
      and session attendance in one study. Interventions that included collaborative
      goal-setting were associated with improved metabolic outcomes and self-efficacy.
      Telehealth and face-to-face diabetes interventions are both promising strategies
      for rural communities. Effective interventions included collaborative goal
      setting. Intervention dose was linked to better outcomes and higher attendance.

PMID- 25948499
TI  - Aphidicolin inhibits cell proliferation via the p53-GADD45beta pathway in AtT-20
      cells.
AB  - Cushing's disease is primarily caused by pituitary corticotroph adenomas, which
      autonomically secrete adrenocorticotropic hormone (ACTH). ACTH production may be
      associated with tumor cell proliferation; however, the effects of cell cycle
      progression on ACTH production and cell proliferation are little known in
      corticotroph tumor cells. A DNA polymerase inhibitor, aphidicolin, arrests cells
      at the entrance to the S phase and blocks the cell cycle; aphidicolin also
      induces apoptosis in tumor cells. In the present study, we determined ACTH
      production and cell proliferation of AtT-20 corticotroph tumor cells following
      treatment with aphidicolin. Aphidicolin decreased proopiomelanocortin mRNA levels
      in AtT-20 cells and the levels of ACTH in the culture medium of these cells.
      Aphidicolin also decreased cell proliferation and induced apoptosis in AtT-20
      cells. Fluorescence-activated cell sorting analyses revealed that this agent
      increased the percentage of G0/G1 phase cells, and decreased S phase cells.
      Aphidicolin decreased the phosphorylation of cyclic adenosine monophosphate
      response element-binding protein and Akt. Aphidicolin increased the levels of
      tumor protein 27 (p27) and 53 (p53), while it decreased cyclin E levels.
      Aphidicolin also increased the mRNA levels of the stress response gene growth
      arrest and DNA damage-inducible 45beta (GADD45beta), a putative downstream target
      of p53. The p53 knockdown increased GADD45beta mRNA levels. The GADD45beta
      knockdown inhibited the decreases in cell proliferation. Thus, aphidicolin
      inhibits cell proliferation via the p53-GADD45beta pathway in AtT-20 cells. 

PMID- 25948498
TI  - Electronic coupling of the phycobilisome with the orange carotenoid protein and
      fluorescence quenching.
AB  - Using computational modeling and known 3D structure of proteins, we arrived at a
      rational spatial model of the orange carotenoid protein (OCP) and phycobilisome
      (PBS) interaction in the non-photochemical fluorescence quenching. The site of
      interaction is formed by the central cavity of the OCP monomer in the capacity of
      a keyhole to the characteristic external tip of the phycobilin-containing domain
      (PB) and folded loop of the core-membrane linker LCM within the PBS core. The
      same central protein cavity was shown to be also the site of the OCP and
      fluorescence recovery protein (FRP) interaction. The revealed geometry of the OCP
      to the PBLCM attachment is believed to be the most advantageous one as the LCM,
      being the major terminal PBS fluorescence emitter, gathers, before quenching by
      OCP, the energy from most other phycobilin chromophores of the PBS. The distance
      between centers of mass of the OCP carotenoid 3'-hydroxyechinenone (hECN) and the
      adjacent phycobilin chromophore of the PBLCM was determined to be 24.7 A. Under
      the dipole-dipole approximation, from the point of view of the determined mutual
      orientation and the values of the transition dipole moments and spectral
      characteristics of interacting chromophores, the time of the direct energy
      transfer from the phycobilin of PBLCM to the S1 excited state of hECN was
      semiempirically calculated to be 36 ps, which corresponds to the known
      experimental data and implies the OCP is a very efficient energy quencher. The
      complete scheme of OCP and PBS interaction that includes participation of the FRP
      is proposed.

PMID- 25948500
TI  - Applications of plasmonics: general discussion.

PMID- 25948501
TI  - Severe human poisoning with a flufenoxuron-containing insecticide: Report of a
      case with transient myocardial dysfunction and review of the literature.
AB  - CONTEXT: Flufenoxuron (CascadeTM) is a new benzoylurea insecticide. We describe a
      case of human poisoning with previously unreported cardiac complications and
      review other case reports in the literature. CASE DETAILS: A 54-year-old
      stuporous man who had ingested a flufenoxuron-containing insecticide presented to
      the emergency department with severely unstable vital signs and lactic acidosis
      which continued to worsen over time. He was treated with gastric lavage and
      infusion of sodium bicarbonate, crystalloid, and dopamine. The patient was
      initially unresponsive, but recovered from shock after norepinephrine treatment.
      While electrocardiography showed no abnormal findings, cardiac enzymes remained
      elevated for several days. Initial echocardiography showed global left
      ventricular hypokinesia and a left ventricular ejection fraction of 40%, but
      echocardiography after 45 h showed normal results. On the sixth day, he was
      discharged after rejecting medical advice for further evaluation. DISCUSSION:
      Severe lactic acidosis, shock, elevation of cardiac enzymes, and global left
      ventricular hypokinesia can occur in human poisoning with flufenoxuron-containing
      insecticide, and norepinephrine is preferable for the management of shock.

PMID- 25948502
TI  - Frailty prevalence and related factors in the older adult-FrailTURK Project.
AB  - Frailty is one of the geriatric syndromes and has an important relationship with
      mortality and morbidity. The aim of this study is to present the characteristics,
      prevalence, and related factors of frailty in older adults in our country. The
      study included 1126 individuals over 65 years of age from 13 centers. Frailty was
      evaluated using the Fried Frailty criteria, and patients were grouped as "frail,"
      "pre-frail," and "non-frail." Nutritional status was assessed with "Mini
      Nutritional Test," psychological status with the "Center for Epidemiological
      Studies Depression Scale-CES-D," and additional diseases with the "Charlson
      Comorbidity index." Approximately 66.5 % of the participants were between 65 and
      74 years of age and 65.7 % were women. Some 39.2 and 43.3 % of the participants
      were rated as frail and pre-frail, respectively. The multinomial logistic
      regression analysis was used to determine the factors associated with frailty. It
      was observed that age, female gender, low education level, being a housewife,
      living with the family, being sedentary, presence of an additional disease, using
      4 or more drugs/day, avoiding to go outside, at least one visit to any emergency
      department within the past year, hospitalization within the past year, non
      functional ambulation, and malnutrition increased the risk of frailty (p < 0.05).
      Establishing the factors associated with frailty is highly important for both
      clinical practice and national economy. This is the first study on this subject
      in our country and will provide guidance in determining treatment strategies.

PMID- 25948503
TI  - Yolk-shell Fe2O3 ? C composites anchored on MWNTs with enhanced lithium and
      sodium storage.
AB  - A unique architecture with yolk-shell Fe2O3 ? C composites attached to the
      surface of MWNTs is designed. Benefiting from the good electrical conductivity of
      MWNTs and carbon layers, as well as the large void space to accommodate the
      volume expansion/extraction of Fe2O3 during battery cycling, the obtained
      MWNT@Fe2O3 ? C exhibited outstanding lithium and sodium storage performance. 

PMID- 25948504
TI  - Investigating the molecular and aggregated states of a drug molecule rutaecarpine
      using spectroscopy, microscopy, crystallography and computational studies.
AB  - The photophysical properties of a potential drug molecule rutaecarpine have been
      investigated in molecular as well as aggregated states. All systems have been
      characterized by various spectroscopic, microscopic and dynamic light scattering
      (DLS) techniques. The investigation has been carried out by keeping the fact in
      mind that hydrophobic organic molecules have a strong tendency to form aggregates
      in aqueous solution. A blue shift in the absorption spectrum of rutaecarpine has
      been observed for aggregates (compared to molecular solution) indicating the
      formation of H-type aggregates. The intermolecular interactions responsible for
      such aggregation have been further investigated through crystallographic and
      computational studies. It has been observed that pi-pi stacking interactions
      among the monomer units play an important role in the formation of H-type
      aggregates. Quantum mechanical calculations also substantiate the blue shift in
      the absorption that has been observed for aggregates. In the present case,
      enhanced emission for aggregates as compared to the molecular solution of
      rutaecarpine has also been observed. The observed enhanced emission upon
      aggregation is attributed to the decrease of the non-radiative rate constant
      (knr) upon aggregation. The effect of a surface active ionic liquid (SAIL), 1
      dodecyl-3-methylimidazolium bromide ([C12mim]Br), on the aggregation of
      rutaecarpine has been investigated. Interestingly, in addition to the decrease in
      the particle size, a change in the morphology of the aggregates has also been
      observed with gradual addition of [C12mim]Br to the colloidal solution of
      rutaecarpine. The present study demonstrates that a SAIL can effectively be used
      as a medium for dissociation of colloidal aggregates and encapsulation of
      molecular species, which in turn would be helpful in influencing the drug
      activity. 

PMID- 25948507
TI  - Is the yellow card road going in the right direction?

PMID- 25948506
TI  - Scientific and Regulatory Policy Committee (SRPC) Points to Consider:
      Histopathology Evaluation of the Pubertal Development and Thyroid Function Assay
      (OPPTS 890.1450, OPPTS 890.1500) in Rats to Screen for Endocrine Disruptors.
AB  - The U.S. Environmental Protection Agency Endocrine Disruptor Screening Program
      (EDSP) is a multitiered approach to determine the potential for environmental
      chemicals to alter the endocrine system. The Pubertal Development and Thyroid
      Function in Intact Juvenile/Peripubertal Female and Male Rats (OPPTS 890.1450,
      890.1500) are 2 of the 9 EDSP tier 1 test Guidelines, which assess upstream
      mechanistic pathways along with downstream morphological end points including
      histological evaluation of the kidneys, thyroid, and select male/female
      reproductive tissues (ovaries, uterus, testes, and epididymides). These assays
      are part of a battery of in vivo and in vitro screens used for initial detection
      of test article endocrine activity. In this Points to Consider article, we
      describe tissue processing, evaluation, and nomenclature to aid in
      standardization of assay results across laboratories. Pubertal assay end points
      addressed include organ weights, estrous cyclicity, clinical pathology, hormonal
      assays, and histological evaluation. Potential treatment-related findings that
      may indicate endocrine disruption are reviewed. Additional tissues that may be
      useful in assessment of endocrine disruption (vagina, mammary glands, and liver)
      are discussed. This Points to Consider article is intended to provide information
      for evaluating peripubertal tissues within the context of individual assay end
      points, the overall pubertal assay, and tier I assays of the EDSP program. 

PMID- 25948508
TI  - Two-spotted spider mite and its natural enemies on strawberry grown as protected
      and unprotected crops in Norway and Brazil.
AB  - Cultivation of strawberry in plastic tunnels has increased considerably in Norway
      and in southeastern Brazil, mainly in an attempt to protect the crop from
      unsuitable climatic factors and some diseases as well as to allow growers to
      expand the traditional production season. It has been hypothesized that
      cultivation under tunnels could increase the incidence of one of its major pests
      in many countries where strawberry is cultivated, including Norway and Brazil,
      the two spotted spider mite, Tetranychus urticae. The objective of this study was
      to evaluate the effect of the use of tunnels on the incidence of T. urticae and
      on its natural enemies on strawberry in two ecologically contrasting regions,
      Norway (temperate) and southeastern Brazil (subtropical). In both countries, peak
      densities of T. urticae in tunnels and in the open fields were lower than
      economic thresholds reported in the literature. Factors determining that
      systematically seem to be the prevailing relatively low temperature in Norway and
      high relative humidity in both countries. The levels of occurrence in Norway and
      Brazil in 2010 were so low that regardless of any potential effect of the use of
      tunnel, no major differences were observed between the two cropping systems in
      relation to T. urticae densities. In 2009 in Norway and in 2011 in Brazil,
      increase in T. urticae population seemed to have been restrained mainly by
      rainfall in the open field and by predatory mites in the tunnels. Phytoseiids
      were the most numerous predatory mite group of natural occurrence on strawberry,
      and the prevalence was higher in Brazil, where the most abundant species on
      strawberry leaves were Neoseiulus anonymus and Phytoseiulus macropilis. In
      Norway, the most abundant naturally occurring phytoseiids on strawberry leaves
      were Typhlodromus (Anthoseius) rhenanus and Typhlodromus (Typhlodromus) pyri.
      Predatory mites were very rare in the litter samples collected in Norway.
      Infection rate of the pest by the fungus Neozygites floridana (Neozygitaceae) was
      low. The results of this work suggest that in Norway the use of tunnels might not
      affect the population densities of T. urticae on strawberry in years of lower
      temperatures. When temperature is not a limiting factor for the development of T.
      urticae in that country (apparently always the case in southern Brazil),
      strawberry cultivation in the tunnels may allow T. urticae to reach higher
      population levels than in open fields (because of the provided protection from
      the direct impact of rainfall), but natural enemies may prevent higher levels
      from being reached. 

PMID- 25948509
TI  - Pseudohallucinations versus hallucinations: wherein lies the difference?
AB  - OBJECTIVE: This paper firstly explores the historical concept of
      pseudohallucinations and their phenomenology. It then examines the experience of
      hallucinosis in two subject groups, one with post-traumatic stress disorder with
      dissociative symptoms and the second with schizophrenia. METHOD: The two groups
      were assessed using the Psychotic Symptoms Rating Scale with a view to
      identifying differences in the hallucinatory and delusional experience. RESULTS:
      There was no significant difference between the groups in loudness, control,
      position, duration, or frequency of the voices. Delusions and negative content
      differed significantly, however. CONCLUSIONS: Researchers have started to
      describe pseudohallucinations along a continuum. We build on this dimensional
      approach and suggest a collaborative nomenclature for subtyping.

PMID- 25948510
TI  - Day program for young people with anorexia nervosa.
AB  - OBJECTIVES: This study examined changes in body mass index (BMI), anorectic
      cognitions, and psychological distress following day program treatment. METHODS:
      Participants were 42 female patients from the Monash Health Butterfly eating
      disorder day program, with anorexia nervosa (AN) restricting type (n = 35) or AN
      binge-eating/purging type (n = 7), ranging from 12 to 24 years. RESULTS:
      Participants' BMI increased significantly over time. Higher motivation at intake
      predicted a greater increase in BMI over time, compared to those with lower
      motivation at intake. There were also significant reductions in drive for
      thinness, body dissatisfaction, anxiety, and depression scores, and improved
      motivation following two, four and six months of treatment. CONCLUSIONS: These
      findings provide further evidence that day programs can assist in weight
      restoration and improvements in psychological aspects of AN in adolescents and
      young adults.

PMID- 25948511
TI  - JMJD1A is a signal-sensing scaffold that regulates acute chromatin dynamics via
      SWI/SNF association for thermogenesis.
AB  - Histone 3 lysine 9 (H3K9) demethylase JMJD1A regulates beta-adrenergic-induced
      systemic metabolism and body weight control. Here we show that JMJD1A is
      phosphorylated at S265 by protein kinase A (PKA), and this is pivotal to activate
      the beta1-adrenergic receptor gene (Adrb1) and downstream targets including Ucp1
      in brown adipocytes (BATs). Phosphorylation of JMJD1A by PKA increases its
      interaction with the SWI/SNF nucleosome remodelling complex and DNA-bound
      PPARgamma. This complex confers beta-adrenergic-induced rapid JMJD1A recruitment
      to target sites and facilitates long-range chromatin interactions and target gene
      activation. This rapid gene induction is dependent on S265 phosphorylation but
      not on demethylation activity. Our results show that JMJD1A has two important
      roles in regulating hormone-stimulated chromatin dynamics that modulate
      thermogenesis in BATs. In one role, JMJD1A is recruited to target sites and
      functions as a cAMP-responsive scaffold that facilitates long-range chromatin
      interactions, and in the second role, JMJD1A demethylates H3K9 di-methylation. 

PMID- 25948512
TI  - Inguinal hernia repair in Switzerland.
AB  - PURPOSE: Inguinal hernia repair is one of the most common procedures in visceral
      surgery, and an important teaching operation for residents during their first
      years. A variety of surgical approaches is currently available, including open
      surgery with or without mesh and laparoscopic surgery. Here we assessed the
      current clinical practice for inguinal hernia surgery in Switzerland and the
      impact on training of surgical residents. METHODS: An anonymous online survey was
      performed among surgical clinics of the Swiss Society of Visceral Surgery (SSVS).
      RESULTS: The overall response rate was 51 %. Nearly all hernia repairs are
      performed with prosthetic material, and only 3.2 % of the procedures use no mesh.
      Overall, open surgery is used for 58.5 % of hernias and 41.5 % are operated
      laparoscopically. In laparoscopic surgery, TEP is the first choice. Overall, the
      Lichtenstein repair is the classical teaching operation performed by residents in
      77.3 % of cases. In contrast to open surgery, laparoscopic hernia repair is not a
      training operation and residents perform only 9.7 % of laparoscopic hernia
      repairs. CONCLUSION: The survey confirms the use of prosthetic material as the
      standard, and the Lichtenstein repair as the first choice for primary inguinal
      hernia repair. The popularity of laparoscopic hernia surgery is increasing at the
      price of less teaching operations available for young residents.

PMID- 25948513
TI  - Altered distribution of HMGB1 in the periodontal ligament of periostin-deficient
      mice subjected to Waldo's orthodontic tooth movement.
AB  - Periostin is essential for the integrity and function of the periodontal ligament
      (PDL), and periostin knockout is related to an enhanced inflammatory status in
      PDL. High mobility group box 1 (HMGB1), a late inflammatory cytokine, is up
      regulated in PDL cells in response to mechanical stress. This study aimed to
      investigate the effect of periostin deficiency (Pn-/-) on HMGB1 expression in PDL
      during orthodontic tooth movement. We used 8-week-old male mice homozygous for
      the disrupted periostin gene and their wild-type (WT) littermates. Tooth movement
      was performed according to Waldo's method, in which 0.5-mm-thick elastic bands
      were inserted between the first and second upper molars of anesthetized mice.
      After 3 days of mechanical loading, mice were fixed by transcardial perfusion of
      4% paraformaldehyde in phosphate buffer, and the maxilla was extracted for
      histochemical analyses. Compared with the WT group, Pn-/- mice showed higher
      basal expression of HMGB1 in the absence of mechanical loading. Following 3 days
      of orthodontic tooth movement, the PDL in the compression side of both groups was
      almost replaced by cell-free hyaline zones, and Pn-/- mice showed a much wider
      residual PDL than WT mice. In the tension side, the number of HMGB1-positive
      cells in PDL in both Pn-/- and WT groups increased remarkably without a
      significant difference between the two groups. Our findings suggest an inhibitory
      effect of periostin on HMGB1 production by PDL and confirmed the critical role of
      periostin in integrity of PDL collagen fibrils during orthodontic tooth movement,
      although mechanical loading is the predominant stimulant of HMGB1 expression
      relative to periostin deficiency.

PMID- 25948515
TI  - Clinically relevant effectiveness of focused extracorporeal shock wave therapy in
      the treatment of chronic plantar fasciitis: a randomized, controlled multicenter
      study.
AB  - BACKGROUND: The effectiveness of extracorporeal shock wave therapy in the
      treatment of plantar fasciitis is controversial. The objective of the present
      study was to test whether focused extracorporeal shock wave therapy is effective
      in relieving chronic heel pain diagnosed as plantar fasciitis. METHODS: Two
      hundred and fifty subjects were enrolled in a prospective, multicenter, double
      blind, randomized, and placebo-controlled U.S. Food and Drug Administration
      trial. Subjects were randomized to focused extracorporeal shock wave therapy
      (0.25 mJ/mm(2)) or placebo intervention, with three sessions of 2000 impulses in
      weekly intervals. Primary outcomes were both the percentage change of heel pain
      on the visual analog scale composite score (pain during first steps in the
      morning, pain with daily activities, and pain with a force meter) and the Roles
      and Maudsley score at twelve weeks after the last intervention compared with the
      scores at baseline. RESULTS: Two hundred and forty-six patients (98.4%) were
      available for intention-to-treat analysis at the twelve-week follow-up. With
      regard to the first primary end point, the visual analog scale composite score,
      there was a significant difference (p = 0.0027, one-sided) in the reduction of
      heel pain in the extracorporeal shock wave therapy group (69.2%) compared with
      the placebo therapy group (34.5%). Extracorporeal shock wave therapy was also
      significantly superior to the placebo therapy for the Roles and Maudsley score (p
      = 0.0006, one-sided). Temporary pain and swelling during and after treatment were
      the only device-related adverse events observed. CONCLUSIONS: The results of the
      present study provide proof of the clinically relevant effect size of focused
      extracorporeal shock wave therapy without local anesthesia in the treatment of
      recalcitrant plantar fasciitis, with success rates between 50% and 65%. LEVEL OF
      EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 25948517
TI  - Current failure mechanisms after knee arthroplasty have changed: polyethylene
      wear is less common in revision surgery.
AB  - BACKGROUND: The present study was designed to clarify which underlying
      indications can be currently considered the main reasons for failure after total
      knee arthroplasty as a function of time. METHODS: We conducted a retrospective
      study that included all first revisions of total knee replacements during 2005 to
      2010 at two high-volume arthroplasty centers. A revision was defined as the
      replacement of at least one prosthetic component. In the descriptive analysis,
      polyethylene wear, aseptic loosening, periprosthetic infection, malalignment,
      instability, arthrofibrosis, extensor mechanism deficiency, periprosthetic
      fracture, and retropatellar arthritis were given as the failure mechanism
      associated with an early, intermediate, or late time interval (less than one
      year, one to three years, and more than three years, respectively) after the
      index total knee arthroplasty. RESULTS: Three hundred and fifty-eight revision
      total knee arthroplasties were included. Of those revisions, 19.8% were performed
      within the first year after the index arthroplasty. The most common indications
      for revision, besides aseptic loosening (21.8%), were instability (21.8%),
      malalignment (20.7%), and periprosthetic infection (14.5%). Revisions due to
      polyethylene wear (7%) rarely occurred. In the early failure group, the primary
      causes of revision were periprosthetic infection (26.8%) and instability (23.9%).
      In the intermediate group, instability (23.3%) and malalignment (29.4%) required
      revision surgery, whereas late failure mechanisms were aseptic loosening (34.7%),
      instability (18.5%), and polyethylene wear (18.5%). CONCLUSIONS: Aseptic
      loosening, instability, malalignment, and periprosthetic infection continue to be
      the primary failure mechanisms leading to revision surgery. Contrary to previous
      literature, the results in the present study showed a substantial reduction in
      implant-associated revisions such as those due to polyethylene wear. Failure
      mechanisms that occur persistently early and in the intermediate term, such as
      periprosthetic infection, instability, and malalignment, remain common causes of
      revision surgery. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for
      Authors for a complete description of levels of evidence.

PMID- 25948514
TI  - Modulation of cholesterol-related gene expression by ergosterol and ergosterol
      enriched extracts obtained from Agaricus bisporus.
AB  - PURPOSE: To investigate the effect of two extracts obtained from Agaricus
      bisporus on the mRNA expression of cholesterol-related genes. One of the extracts
      contained ergosterol and other fungal sterols (SFE) and the other contained beta
      glucans and fungal sterols (EbetaG). METHODS: Firstly, the dietary mixed micelles
      (DMMs) generated after in vitro digestion of standards and SFE were applied to
      Caco2 cells. Then, the lower compartment after a Caco2-transport experiment was
      applied to HepG2 cells. The mRNA expression was assessed in both cell lines by
      low-density arrays (LDA). Mice received the extracts, ergosterol or control drugs
      after 4 weeks of a high-cholesterol diet. The lipid profile of plasma, liver and
      feces was determined. LDA assays were performed in liver and intestines. RESULTS:
      The DMM fraction of SFE up-regulated the LDLR mRNA expression in Caco2 cells. The
      lower compartment after Caco2-transport experiments up-regulated LDLR and
      modulated several other lipid-related genes in HepG2 cells. In mice, SFE
      decreased TC/HDL ratio and reduced hepatic triglycerides paralleled with down
      regulation of Dgat1 expression, while EbetaG did it without transcriptional
      changes. Addition of SFE or ergosterol induced in jejunum a similar
      transcriptional response to simvastatin and ezetimibe; they all down-regulated
      Srebf2 and Nr1h4 (FXR) genes. CONCLUSION: Ergosterol-containing extracts from A.
      bisporus lowered hepatic triglyceride and modify the mRNA expression of
      cholesterol-related genes although the transcriptional regulation was unrelated
      to changes in plasma lipid profile. These extracts may be useful limiting hepatic
      steatosis and as bioactive ingredients to design novel functional foods
      preventing lifestyle-related diseases such as non-alcoholic fatty liver disease.

PMID- 25948516
TI  - MRI for the evaluation of knee pain: comparison of ordering practices of primary
      care physicians and orthopaedic surgeons.
AB  - BACKGROUND: Knee pain is one of the most common reasons for outpatient visits in
      the U.S. The great majority of such cases can be effectively evaluated through
      physical examination and judicious use of radiography. Despite this, an
      increasing number of magnetic resonance images (MRIs) of the knee are being
      ordered for patients with incomplete work-ups or for inappropriate indications.
      We hypothesized that MRIs ordered by orthopaedic providers were more likely to
      result in changes in diagnoses and/or plans for care than those ordered by non
      orthopaedic providers. METHODS: We reviewed the charts of all consecutive new
      patients seen at our orthopaedic outpatient office between January 1, 2010, and
      December 31, 2011, with International Classification of Diseases, Ninth Revision
      (ICD-9) codes for meniscal or unspecific sprains and strains of the knee. A total
      of 1592 patients met our inclusion criteria and were divided into two groups:
      those initially evaluated and referred by their primary care physician (PCP) (n =
      747) and those initially evaluated by one of our staff orthopaedic surgeons (n =
      845). RESULTS: MRI-ordering rates were nearly identical between orthopaedic
      surgeons and PCPs (25.0% versus 24.8%; p = 0.945). MRIs ordered by orthopaedic
      surgeons, however, resulted in significantly more arthroscopic interventions than
      those ordered by PCPs (41.2% versus 31.4%; p = 0.042). Orthopaedic surgeons
      ordered MRIs for patients who were more likely to benefit from arthroscopic
      intervention, including patients who were younger (mean age, 45.1 years versus
      56.5 years for those with PCP-ordered MRIs; p < 0.001), patients with acute
      symptoms (39.3% versus 22.2%; p < 0.001), and patients with a history of trauma
      (49.3% versus 36.2%; p = 0.019). Finally, orthopaedic surgeons were less likely
      than PCPs to order MRIs for patients with substantial osteoarthritis who
      subsequently underwent total knee arthroplasty (4.3% versus 9.2%; p = 0.048).
      CONCLUSIONS: MRI utilization by orthopaedic surgeons results in more appropriate
      interventions for patients with symptoms and findings most amenable to surgical
      intervention.

PMID- 25948518
TI  - Fluoroscopic radiation exposure: are we protecting ourselves adequately?
AB  - BACKGROUND: While traditional intraoperative fluoroscopy protection relies on
      thyroid shields and aprons, recent data suggest that the surgeon's eyes and hands
      receive more exposure than previously appreciated. Using a distal radial fracture
      surgery model, we examined (1) radiation exposure to the eyes, thyroid, chest,
      groin, and hands of a surgeon mannequin; (2) the degree to which shielding
      equipment can decrease exposure; and (3) how exposure varies with fluoroscopy
      unit size. METHODS: An anthropomorphic model was fit with radiation-attenuating
      glasses, a thyroid shield, an apron, and gloves. "Exposed" thermoluminescent
      dosimeters overlaid the protective equipment at the eyes, thyroid, chest, groin,
      and index finger while "shielded" dosimeters were placed beneath the protective
      equipment. Fluoroscopy position and settings were standardized. The mini-c-arm
      milliampere-seconds were fixed based on the selection of the kilovolt peak (kVp).
      Three mini and three standard c-arms scanned a model of the patient's wrist
      continuously for fifteen minutes each. Ten dosimeter exposures were recorded for
      each c-arm. RESULTS: Hand exposure averaged 31 MUSv/min (range, 22 to 48
      MUSv/min), which was 13.0 times higher than the other recorded exposures. Eye
      exposure averaged 4 MUSv/min, 2.2 times higher than the mean thyroid, chest, and
      groin exposure. Gloves reduced hand exposure by 69.4%. Glasses decreased eye
      exposure by 65.6%. There was no significant difference in exposure between mini
      and standard fluoroscopy. CONCLUSIONS: Surgeons' hands receive the most radiation
      exposure during distal radial plate fixation under fluoroscopy. There was a small
      but insignificant difference in mean exposure between standard fluoroscopy and
      mini-fluoroscopy, but some standard units resulted in lower exposure than some
      mini-units. On the basis of these findings, we recommend routine protective
      equipment to mitigate exposure to surgeons' hands and eyes, in addition to the
      thyroid, chest, and groin, during fluoroscopy procedures.

PMID- 25948519
TI  - Rotational Acetabular Osteotomy for Osteoarthritis with Acetabular Dysplasia:
      Conversion Rate to Total Hip Arthroplasty within Twenty Years and Osteoarthritis
      Progression After a Minimum of Twenty Years.
AB  - BACKGROUND: We investigated the rate of conversion to total hip arthroplasty by
      twenty years and radiographic findings at a minimum of twenty years after
      rotational acetabular osteotomy. METHODS: Between June 1986 and August 1991, we
      performed 172 rotational acetabular osteotomies in 168 patients with acetabular
      dysplasia. Of those, ninety-three hips (ninety-one patients), including twenty
      three hips with pre-osteoarthritis, twenty-nine with initial osteoarthritis, and
      forty-one with advanced osteoarthritis, had clinical and radiographic findings
      available. The mean age of the patients was 32.4 years (range, twelve to forty
      nine years). The duration of follow-up was a mean of twenty-three years (range,
      twenty to twenty-seven years) for seventy-six hips, excluding hips that underwent
      conversion to total hip arthroplasty. RESULTS: Conversion to total hip
      arthroplasty by twenty years after surgery was performed in one hip (4%) with pre
      osteoarthritis, two hips (7%) with initial osteoarthritis, and fourteen hips
      (34%) with advanced osteoarthritis. The hips with advanced osteoarthritis had a
      significantly higher rate of conversion to total hip arthroplasty than hips in
      the other stages did (p = 0.0005). At the latest follow-up or at conversion to
      total hip arthroplasty, the disease stage had not progressed in seventeen hips
      (74%) with pre-osteoarthritis, nineteen (66%) with initial osteoarthritis, and
      twenty-six (63%) with advanced osteoarthritis. CONCLUSIONS: The progression of
      osteoarthritis after rotational acetabular osteotomy was not detected for at
      least twenty years in most hips with either pre-osteoarthritis or initial
      osteoarthritis in this cohort. Rotational acetabular osteotomy may delay
      conversion to total hip arthroplasty in advanced osteoarthritis. LEVEL OF
      EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 25948520
TI  - Locking plate placement with unicortical screw fixation adjunctive to
      intramedullary rodding in long bones of patients with osteogenesis imperfecta.
AB  - BACKGROUND: Intramedullary rodding has been the mainstay of long-bone
      stabilization in osteogenesis imperfecta. However, in some cases, intramedullary
      rodding cannot provide adequate fixation because of a lack of rotational control
      and thin diameter of long bones. We have applied adjunctive unicortical locking
      plate fixation in selected cases of osteogenesis imperfecta to address these
      biomechanical issues. METHODS: Thirty-seven bone segments of twenty-four patients
      with osteogenesis imperfecta (ten type III, nine type IV, three type I, and two
      type V), in which unicortical locking plate fixation was applied adjunctive to
      intramedullary rodding and was later removed after union had been achieved, were
      the study subjects. The mean patient age at the time of surgery was 15.5 years
      (range, 6.2 to 39.8 years). Medical records and follow-up radiographs were
      reviewed to evaluate healing, complications, and the fates of screw holes after
      plate removal. RESULTS: All fractures or osteotomies healed completely. Locking
      plates were removed postoperatively at a mean time (and standard deviation) of
      1.8 +/- 0.9 years (range, 0.3 to 3.8 years). In seven of the thirty-seven cases,
      fractures through the screw hole occurred; all of these were treated
      conservatively. In eighteen of nineteen cases that were followed for more than a
      year after plate removal without screw hole-related complication, screw holes
      healed and were no longer visualized by radiography. CONCLUSIONS: Unicortical
      locking plate fixation effectively supplements intramedullary rod fixation in
      selected cases of osteogenesis imperfecta. LEVEL OF EVIDENCE: Therapeutic Level
      IV. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 25948521
TI  - Hemicortical resection and inlay allograft reconstruction for primary bone
      tumors: a retrospective evaluation in the Netherlands and review of the
      literature.
AB  - BACKGROUND: Selected primary tumors of the long bones can be adequately treated
      with hemicortical resection, allowing for optimal function without compromising
      the oncological outcome. Allografts can be used to reconstruct the defect. As
      there is a lack of studies of larger populations with sufficient follow-up,
      little is known about the outcomes of these procedures. METHODS: In this
      nationwide retrospective study, all patients treated with hemicortical resection
      and allograft reconstruction for a primary bone tumor from 1989 to 2012 were
      evaluated for (1) mechanical complications and infection, (2) oncological
      outcome, and (3) failure or allograft survival. The minimum duration of follow-up
      was twenty-four months. RESULTS: The study included 111 patients with a median
      age of twenty-eight years (range, seven to seventy-three years). The predominant
      diagnoses were adamantinoma (n = 37; 33%) and parosteal osteosarcoma (n = 18;
      16%). At the time of review, 104 patients (94%) were alive (median duration of
      follow-up, 6.7 years). Seven patients (6%) died, after a median of twenty-six
      months. Thirty-seven patients (33%) had non-oncological complications, with host
      bone fracture being the most common (n = 20, 18%); all healed uneventfully. Other
      complications included nonunion (n = 8; 7%), infection (n = 8; 7%), and allograft
      fracture (n = 3; 3%). Of ninety-seven patients with a malignant tumor, fifteen
      (15%) had residual or recurrent tumor and six (6%) had metastasis. The risk of
      complications and fractures increased with the extent of cortical resection.
      CONCLUSIONS: Survival of hemicortical allografts is excellent. Host bone fracture
      is the predominant complication; however, none of these fractures necessitated
      allograft removal in our series. The extent of resection is the most important
      risk factor for complications. Hemicortical resection is not recommended for high
      grade lesions; however, it may be superior to segmental resection for treatment
      of carefully selected tumors, provided that it is possible to obtain adequate
      margins. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors
      for a complete description of levels of evidence.

PMID- 25948523
TI  - Acetabular fractures in the elderly: evaluation and management.
AB  - Acetabular fracture patterns in the elderly, with increased involvement of the
      anterior column, quadrilateral plate comminution, medialization of the femoral
      head, and marginal impaction, differ from those noted among a younger cohort.
      Poor prognostic factors for open reduction and internal fixation (ORIF) are
      posterior wall comminution, marginal impaction of the acetabulum, a femoral head
      impaction fracture, a so-called gull sign, and hip dislocation. The rate of
      conversion to total hip arthroplasty following formal ORIF has been reported to
      be 22% at a mean of twenty-nine months. Total hip replacement after an acetabular
      fracture generally yields good clinical results; however, in the acute setting,
      it must be combined with proper stable fracture fixation.

PMID- 25948524
TI  - Improving Value in Musculoskeletal Care Delivery: AOA Critical Issues.
AB  - Improving value in musculoskeletal health care has emerged as an important
      objective in both the United States and Canada. In order to achieve this
      objective, providers need to have a clear definition of value and an
      infrastructure for measuring outcomes of interest to patients and costs over the
      episode of care. Although national patient registries have been established in
      the United States and Canada, they nevertheless lag behind other registries
      worldwide in terms of collecting patient-reported outcomes and capturing data
      from a wide cross-section of hospitals and physicians. With the help of
      professional medical societies and the creation of national initiatives, patient
      reported outcomes data collection on a large scale may be possible, but many
      challenges remain regarding implementation. Alternatives to the fee-for-service
      payment model, including pay-for-reporting and pay-for-performance, may help
      incentivize physicians and health-care providers to obtain and improve on patient
      reported outcomes data collection. Other payment reforms, such as bundled
      payments, have been piloted in certain regions, but their sustainability and long
      term success are unclear at this time. Novel health-care delivery strategies
      aimed at improving quality, coordinating multispecialty care, and enhancing
      patient participation in shared decision-making have shown promise in improving
      patient-centered outcomes, but delivery models continue to vary greatly
      throughout the United States and Canada. The current status of musculoskeletal
      health-care delivery requires substantial change before the goal of improving
      patient outcomes and lowering health-care costs can be achieved. 

PMID- 25948525
TI  - Testing basic competency in knee arthroscopy using a virtual reality simulator:
      exploring validity and reliability.
AB  - BACKGROUND: Diagnostic knee arthroscopy is a common procedure that orthopaedic
      residents are expected to learn early in their training. Arthroscopy requires a
      different skill set from traditional open surgery, and many orthopaedic residents
      feel less prepared for arthroscopic procedures. Virtual reality simulation
      training and testing provide an opportunity to ensure basic competency before
      proceeding to supervised procedures in patients. METHODS: Twenty-six physicians
      (thirteen novices and thirteen experienced arthroscopic surgeons) were
      voluntarily recruited to perform a test consisting of five arthroscopic
      procedures on a knee arthroscopy simulator. Performance was evaluated by
      obtaining predefined metrics from the simulator for each procedure, and z-scores,
      describing suboptimal performance, were calculated from the metrics. The
      intercase reliability of the simulator metrics was explored by calculating an
      intraclass correlation coefficient. Finally, a pass-or-fail standard was set with
      use of the contrasting groups method, and the consequences of the pass-or-fail
      standard were explored. RESULTS: One procedure was excluded from the final test
      because of a lack of validity. The total Z-scores for the four procedures
      included in the final test showed an intercase reliability of 0.87 (95%
      confidence interval, 0.78 to 0.93). The total mean z-score (and standard
      deviation) was 38.6 +/- 27.3 points for the novices and 0.0 +/- 9.1 points for
      the experienced surgeons (p < 0.0005). The pass-or-fail standard was set at a
      total z-score of 15.5 points, resulting in two of the novices passing the test
      and a single experienced surgeon failing the test. CONCLUSIONS: By combining four
      procedures on a virtual reality arthroscopy simulator, it was possible to create
      a valid, reliable, and feasible test of basic arthroscopic competency and to
      establish a credible pass-or-fail standard. CLINICAL RELEVANCE: The simulation
      based test and pass-or-fail standard could aid in assessing and ensuring basic
      competency of future orthopaedic residents before proceeding to supervised
      procedures in patients.

PMID- 25948526
TI  - Spinal fusion for scoliosis in patients with globally involved cerebral palsy: an
      ethical assessment.

PMID- 25948527
TI  - A New Approach to Managing Patients with Problematic Metal Hip Implants: The Use
      of an Internet-Enhanced Multidisciplinary Team Meeting. AAOS Exhibit Selection.

PMID- 25948528
TI  - Investigating the Relationship Between Ankle Arthrodesis and Adjacent-Joint
      Arthritis in the Hindfoot. A Systematic Review.

PMID- 25948529
TI  - Is Extracorporeal Shock Wave Therapy an Underutilized Treatment for Chronic
      Plantar Fasciitis? Commentary on an article by Hans Gollwitzer, MD, et al.:
      "Clinically Relevant Effectiveness of Focused Extracorporeal Shock Wave Therapy
      in the Treatment of Chronic Plantar Fasciitis. A Randomized, Controlled
      Multicenter Study".

PMID- 25948530
TI  - Less Is More: Knee MRI Utilization by PCPs Versus Orthopaedic Surgeons:
      Commentary on an article by Timothy T. Roberts, MD, et al.: "MRI for the
      Evaluation of Knee Pain. Comparison of Ordering Practices of Primary Care
      Physicians and Orthopaedic Surgeons".

PMID- 25948531
TI  - Exploiting amphiphilicity: facile metal free access to thianthrenes and related
      sulphur heterocycles.
AB  - Benzodithioloimines are reacted with arynes or alkynes substituted with electron
      withdrawing groups to afford the corresponding thianthrene or
      benzo[b][1,4]dithiine derivatives. The transformation takes place under mild
      reaction conditions without any transition metal. Furthermore, the reaction mode
      could be expanded to 2-thiocyanatopyrroles yielding pyrrolothiazoles. 

PMID- 25948532
TI  - Predicting outcomes among patients with atrial fibrillation and heart failure
      receiving anticoagulation with warfarin.
AB  - Among patients receiving oral anticoagulation for atrial fibrillation (AF), heart
      failure (HF) is associated with poor anticoagulation control. However, it is not
      known which patients with heart failure are at greatest risk of adverse outcomes.
      We evaluated 62,156 Veterans Health Administration (VA) patients receiving
      warfarin for AF between 10/1/06-9/30/08 using merged VA-Medicare dataset. We
      predicted time in therapeutic range (TTR) and rates of adverse events by
      categorising patients into those with 0, 1, 2, or 3+ of five putative markers of
      HF severity such as aspartate aminotransferase (AST)> 80 U/l, alkaline
      phosphatase> 150 U/l, serum sodium< 130 mEq/l, any receipt of metolazone, and any
      inpatient admission for HF exacerbation. These risk categories predicted TTR:
      patients without HF (referent) had a mean TTR of 65.0 %, while HF patients with
      0, 1, 2, 3 or more markers had mean TTRs of 62.2 %, 57.2 %, 53.5 %, and 50.7 %,
      respectively (p< 0.001). These categories also discriminated for major
      haemorrhage well; compared to patients without HF, HF patients with increasing
      severity had hazard ratios of 1.84, 3.06, 3.52 and 5.14 respectively (p< 0.001).
      However, although patients with HF had an elevated hazard for bleeding compared
      to those without HF, these categories did not effectively discriminate risk of
      ischaemic stroke across HF. In conclusion, we developed a HF severity model using
      easily available clinical characteristics that performed well to risk-stratify
      patients with HF who are receiving anticoagulation for AF with regard to major
      haemorrhage. 

PMID- 25948533
TI  - Tumor Necrosis Factor-alpha Underlies Loss of Cortical Dendritic Spine Density in
      a Mouse Model of Congestive Heart Failure.
AB  - BACKGROUND: Heart failure (HF) is a progressive disorder characterized by reduced
      cardiac output and increased peripheral resistance, ultimately leading to tissue
      perfusion deficits and devastating consequences for several organs including the
      brain. We previously described a tumor necrosis factor-alpha (TNF-alpha)
      dependent enhancement of posterior cerebral artery tone and concomitant reduced
      cerebral blood flow in a mouse model of early HF in which blood pressure remains
      minimally affected. HF is often associated with cognitive impairments such as
      memory deficits, even before any overt changes in brain structure and function
      occur. The pathophysiology underlying the development of cognitive impairments in
      HF is unknown, and appropriate treatment strategies are lacking. METHODS AND
      RESULTS: We used a well-established mouse model in which HF was induced by
      experimental myocardial infarction produced by permanent surgical ligation of the
      left anterior descending coronary artery (infarct size ~25% of the left
      ventricular wall). Ligated mice developed enlarged hearts, congested lungs, and
      reduced cardiac output and blood pressure, with elevated peripheral resistance
      within 6 to 8 weeks after ligation. In this study, we demonstrated the
      significance of the proinflammatory cytokine TNF-alpha during HF-mediated
      neuroinflammation and associated impaired hippocampus-independent nonspatial
      episodic memory function. Augmented cerebral TNF-alpha expression and microglial
      activation in HF mice, indicative of brain inflammation, were accompanied by
      morphological changes and significant reduction of cortical dendritic spines
      (61.39+/-8.61% for basal and 61.04+/-9.18% for apical spines [P<0.001]). The
      significance of TNF-alpha signaling during the observed HF-mediated
      neurodegenerative processes is supported by evidence showing that sequestration
      or genetic deletion of TNF-alpha ameliorates the observed reduction of cortical
      dendritic spines (33.51+/-7.63% for basal and 30.13+/-6.98% for apical spines in
      wild-type mice treated with etanercept; 17.09+/-6.81% for basal and 17.21+/-7.29%
      for apical spines in TNF-alpha(-/-)). Moreover, our data suggest that alterations
      in cerebral serum and glucocorticoid-inducible kinase 1 (SgK1) expression and
      phosphorylation during HF may be TNF-alpha dependent and that an increase of SgK1
      phosphorylation potentially plays a role in the HF-associated reduction of
      dendritic spine density. CONCLUSIONS: Our findings demonstrate that TNF-alpha
      plays a pivotal role in HF-mediated neuroinflammation and associated alterations
      of cortical dendritic spine density and has the potential to reveal novel
      treatment strategies for HF-associated memory deficits.

PMID- 25948534
TI  - Ignoring regression to the mean leads to unsupported conclusion about obesity.
AB  - Childhood obesity remains a substantial health concern for our population and
      thoughtful attempts to develop and evaluate the utility of programs to reduce
      childhood obesity levels are needed. Unfortunately, we believe the conclusion by
      Burke et al. that the HealthMPowers program produces positive change in body
      composition is incorrect because the results obtained are likely due to
      regression to the mean (RTM), a well-known threat to the validity of studies that
      is often overlooked. Using empirical data, we demonstrate that RTM is likely to
      be the cause for the changes reported. A more reasonable conclusion than the one
      of effectiveness the authors offered would be that the results did not support
      the effectiveness of the intervention. Public health officials, parents, school
      leaders, community leaders, and regulators need and deserve valid evidence free
      from spin on which they can base decisions. 

PMID- 25948535
TI  - Association between toll-like receptors 9 (TLR9) gene polymorphism and risk of
      pulmonary tuberculosis: meta-analysis.
AB  - BACKGROUND: Previous studies indicated that the single nucleotide polymorphisms
      (SNPs) in TLR9 gene might be associated with Tuberculosis (TB) risk. However, the
      results are inconsistent and inconclusive. METHODS: 1745 articles from four
      databases were involved in our study. A meta-analysis on the associations between
      the seven polymorphisms and TB risk was carried out by comparison using different
      genetic models. RESULTS: In this systematic review 8 studies from seven English
      articles were analyzed. Our results showed that rs352139 is significantly
      associated with TB risk (AA vs. AG, OR 0.77, 95% CI 0.65-0.92, P = 0.004). In the
      ethnic subgroup analysis, Indonesians with AA genotype had a decreased
      susceptibility while Mexicans with GG allele had an increased risk. CONCLUSIONS:
      The meta-analysis indicated that rs352139 polymorphism might be associated with
      decreased TB risk in Indonesians whereas increased risk in Mexicans. Whether the
      observed association was due to causal effect needs to be further studied.

PMID- 25948536
TI  - Identification and distribution of the NBS-LRR gene family in the Cassava genome.
AB  - BACKGROUND: Plant resistance genes (R genes) exist in large families and usually
      contain both a nucleotide-binding site domain and a leucine-rich repeat domain,
      denoted NBS-LRR. The genome sequence of cassava (Manihot esculenta) is a valuable
      resource for analysing the genomic organization of resistance genes in this crop.
      RESULTS: With searches for Pfam domains and manual curation of the cassava gene
      annotations, we identified 228 NBS-LRR type genes and 99 partial NBS genes. These
      represent almost 1% of the total predicted genes and show high sequence
      similarity to proteins from other plant species. Furthermore, 34 contained an N
      terminal toll/interleukin (TIR)-like domain, and 128 contained an N-terminal
      coiled-coil (CC) domain. 63% of the 327 R genes occurred in 39 clusters on the
      chromosomes. These clusters are mostly homogeneous, containing NBS-LRRs derived
      from a recent common ancestor. CONCLUSIONS: This study provides insight into the
      evolution of NBS-LRR genes in the cassava genome; the phylogenetic and mapping
      information may aid efforts to further characterize the function of these
      predicted R genes.

PMID- 25948537
TI  - Assessment of Cerebrovascular Autoregulation Using Regional Cerebral Blood Flow
      in Surgically Managed Brain Trauma Patients.
AB  - BACKGROUND: Impairment of cerebrovascular autoregulation is a risk factor for
      ischemic damage following severe brain injury. Autoregulation can be assessed
      indirectly using intracranial pressure monitoring as a surrogate of cerebral
      blood volume, but this measure may not be applicable to patients following
      decompressive craniectomy. Here, we describe assessment of autoregulation using
      regional cerebral blood flow (rCBF). METHODS: In seven patients with severe brain
      trauma who underwent neurological surgery, a Hemedex(r) rCBF probe was placed
      intraoperatively in peri-lesional tissue. Autoregulation was assessed as a moving
      Pearson correlation between CPP and rCBF (rCBFx). RESULTS: Composite data from
      all patients showed relatively constant perfusion over a wide CPP range (50-90
      mmHg) and a U-shaped autoregulation curve with maximal autoregulation (CPPopt) at
      55-60 mmHg. All rCBF values fell below the ischemic threshold (<18 ml/100 g/min)
      when CPPs were <50 mmHg compared with 11 % ischemia when CPPs >50 mmHg (P <
      0.05). We examined the percent time during which both autoregulation was intact
      and rCBF exceeded the ischemic threshold. In the composite data, this variable
      was maximal in the CPP range of 75-80 mmHg (CPPideal). In individual patients,
      the range of CPPs with intact autoregulation varied widely. Individual CPPopt
      values ranged between 60 and 100 mmHg and CPPideal ranged between 65 and 105
      mmHg. CONCLUSIONS: Assessment of autoregulation with Hemedex(r) rCBF monitor is
      feasible and could be used to guide CPP management strategies to optimize both
      autoregulation and perfusion. Autoregulatory impairment and CPPopt vary
      considerably between patients, and the addition of rCBF monitoring could help
      guide CPP targeting decisions.

PMID- 25948538
TI  - Early detection of anthracycline cardiotoxicity and improvement with heart
      failure therapy.
AB  - BACKGROUND: Three types of anthracycline-induced cardiotoxicities are currently
      recognized: acute, early-onset chronic, and late-onset chronic. However, data
      supporting this classification are lacking. We prospectively evaluated incidence,
      time of occurrence, clinical correlates, and response to heart failure therapy of
      cardiotoxicity. METHODS AND RESULTS: We assessed left ventricular ejection
      fraction (LVEF), at baseline, every 3 months during chemotherapy and for the
      following year, every 6 months over the following 4 years, and yearly afterward
      in a heterogeneous cohort of 2625 patients receiving anthracycline-containing
      therapy. In case of cardiotoxicity (LVEF decrease >10 absolute points, and <50%),
      heart failure therapy was initiated. Recovery from cardiotoxicity was defined as
      partial (LVEF increase >5 absolute points and >50%) or full (LVEF increase to the
      baseline value). The median follow-up was 5.2 (quartile 1 to quartile 3, 2.6-8.0)
      years. The overall incidence of cardiotoxicity was 9% (n=226). The median time
      elapsed between the end of chemotherapy and cardiotoxicity development was 3.5
      (quartile 1 to quartile 3, 3-6) months. In 98% of cases (n=221), cardiotoxicity
      occurred within the first year. Twenty-five (11%) patients had full recovery, and
      160 (71%) patients had partial recovery. At multivariable analysis, end
      chemotherapy LVEF (hazard ratio, 1.37; 95% confidence interval, 1.33-1.42 for
      each percent unit decrement) and cumulative doxorubicin dose (hazard ratio, 1.09;
      95% confidence interval, 1.04-1.15 for each 50 mg/m(2) increment) were
      independent correlates of cardiotoxicity. CONCLUSIONS: Most cardiotoxicity after
      anthracycline-containing therapy occurs within the first year and is associated
      with anthracycline dose and LVEF at the end of treatment. Early detection and
      prompt therapy of cardiotoxicity appear crucial for substantial recovery of
      cardiac function.

PMID- 25948539
TI  - Anthracycline cardiotoxicity: a new paradigm for an old classic.

PMID- 25948540
TI  - Is the 99th Percentile the Optimal Reference Limit to Diagnose Myocardial
      Infarction With High-Sensitivity Cardiac Troponin Assays in Patients With Chronic
      Kidney Disease?

PMID- 25948541
TI  - Misdiagnosis of Myocardial Infarction Related to Limitations of the Current
      Regulatory Approach to Define Clinical Decision Values for Cardiac Troponin.
AB  - BACKGROUND: Misdiagnosis of acute myocardial infarction (AMI) may significantly
      harm patients and may result from inappropriate clinical decision values (CDVs)
      for cardiac troponin (cTn) owing to limitations in the current regulatory
      process. METHODS AND RESULTS: In an international, prospective, multicenter
      study, we quantified the incidence of inconsistencies in the diagnosis of AMI
      using fully characterized and clinically available high-sensitivity (hs) cTn
      assays (hs-cTnI, Abbott; hs-cTnT, Roche) among 2300 consecutive patients with
      suspected AMI. We hypothesized that the approved CDVs for the 2 assays are not
      biologically equivalent and might therefore contribute to inconsistencies in the
      diagnosis of AMI. Findings were validated by use of sex-specific CDVs and
      parallel measurements of other hs-cTnI assays. AMI was the adjudicated diagnosis
      in 473 patients (21%). Among these, 86 patients (18.2%) had inconsistent
      diagnoses when the approved uniform CDV was used. When sex-specific CDVs were
      used, 14.1% of female and 22.7% of male AMI patients had inconsistent diagnoses.
      Using biologically equivalent CDV reduced inconsistencies to 10% (P<0.001). These
      findings were confirmed with parallel measurements of other hs-cTn assays. The
      incidence of inconsistencies was only 7.0% for assays with CDVs that were nearly
      biologically equivalent. Patients with inconsistent AMI had long-term mortality
      comparable to that of patients with consistent diagnoses (P=NS) and a trend
      toward higher long-term mortality than patients diagnosed with unstable angina
      (P=0.05). CONCLUSIONS: Currently approved CDVs are not biologically equivalent
      and contribute to major inconsistencies in the diagnosis of AMI. One of 5 AMI
      patients will receive a diagnosis other than AMI if managed with the alternative
      hs-cTn assay. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT00470587.

PMID- 25948542
TI  - Optimal Cutoff Levels of More Sensitive Cardiac Troponin Assays for the Early
      Diagnosis of Myocardial Infarction in Patients With Renal Dysfunction.
AB  - BACKGROUND: It is unknown whether more sensitive cardiac troponin (cTn) assays
      maintain their clinical utility in patients with renal dysfunction. Moreover,
      their optimal cutoff levels in this vulnerable patient population have not
      previously been defined. METHODS AND RESULTS: In this multicenter study, we
      examined the clinical utility of 7 more sensitive cTn assays (3 sensitive and 4
      high-sensitivity cTn assays) in patients presenting with symptoms suggestive of
      acute myocardial infarction. Among 2813 unselected patients, 447 (16%) had renal
      dysfunction (defined as Modification of Diet in Renal Disease-estimated
      glomerular filtration rate <60 mL.min(-1).1.73 m(-2)). The final diagnosis was
      centrally adjudicated by 2 independent cardiologists using all available
      information, including coronary angiography and serial levels of high-sensitivity
      cTnT. Acute myocardial infarction was the final diagnosis in 36% of all patients
      with renal dysfunction. Among patients with renal dysfunction and elevated
      baseline cTn levels (>=99th percentile), acute myocardial infarction was the most
      common diagnosis for all assays (range, 45%-80%). In patients with renal
      dysfunction, diagnostic accuracy at presentation, quantified by the area under
      the receiver-operator characteristic curve, was 0.87 to 0.89 with no significant
      differences between the 7 more sensitive cTn assays and further increased to 0.91
      to 0.95 at 3 hours. Overall, the area under the receiver-operator characteristic
      curve in patients with renal dysfunction was only slightly lower than in patients
      with normal renal function. The optimal receiver-operator characteristic curve
      derived cTn cutoff levels in patients with renal dysfunction were significantly
      higher compared with those in patients with normal renal function (factor, 1.9
      3.4). CONCLUSIONS: More sensitive cTn assays maintain high diagnostic accuracy in
      patients with renal dysfunction. To ensure the best possible clinical use, assay
      specific optimal cutoff levels, which are higher in patients with renal
      dysfunction, should be considered. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00470587.

PMID- 25948545
TI  - "Value based" payment project saves US nearly $400m in two years, report finds.

PMID- 25948522
TI  - Reliability, validity, and responsiveness of the Western Ontario and McMaster
      Universities Osteoarthritis Index for elderly patients with a femoral neck
      fracture.
AB  - BACKGROUND: The Western Ontario and McMaster Universities Osteoarthritis Index
      (WOMAC) has been extensively evaluated in groups of patients with osteoarthritis,
      yet not in patients with a femoral neck fracture. This study aimed to determine
      the reliability, construct validity, and responsiveness of the WOMAC compared
      with the Short Form-12 (SF-12) and the EuroQol 5D (EQ-5D) questionnaires for the
      assessment of elderly patients with a femoral neck fracture. METHODS: Reliability
      was tested by assessing the Cronbach alpha. Construct validity was determined
      with the Pearson correlation coefficient. Change scores were calculated from ten
      weeks to twelve months of follow-up. Standardized response means and floor and
      ceiling effects were determined. Analyses were performed to compare the results
      for patients less than eighty years old with those for patients eighty years of
      age or older. RESULTS: The mean WOMAC total score was 89 points before the
      fracture in the younger patients and increased from 70 points at ten weeks to 81
      points at two years postoperatively. In the older age group, these scores were
      86, 75, and 78 points. The mean WOMAC pain scores before the fracture and at ten
      weeks and two years postoperatively were 92, 76, and 87 points, respectively, in
      the younger age group and 92, 84, and 93 points in the older age group. Function
      scores were 89, 68, and 79 points for the younger age group and 84, 71, and 73
      points for the older age group. The Cronbach alpha for pain, stiffness, function,
      and the total scale ranged from 0.83 to 0.98 for the younger age group and from
      0.79 to 0.97 for the older age group. Construct validity was good, with 82% and
      79% of predefined hypotheses confirmed in the younger and older age groups,
      respectively. Responsiveness was moderate. No floor effects were found. Moderate
      to large ceiling effects were found for pain and stiffness scales at ten weeks
      and twelve months in younger patients (18% to 36%) and in the older age group
      (38% to 53%). CONCLUSIONS: The WOMAC showed good reliability, construct validity,
      and responsiveness in both age groups of elderly patients with a femoral neck
      fracture who had been physically and mentally fit before the fracture. The
      instrument is suitable for use in future clinical studies in these populations.
      CLINICAL RELEVANCE: The results are based on two clinical trials. The
      questionnaires used concern pure, clinically relevant issues (ability to walk,
      climb stairs, etc.). Moreover, the results can be used for future research
      comparing clinical outcomes (or treatments) for populations with a femoral neck
      fracture.

PMID- 25948543
TI  - Hypertension prevalence, awareness, treatment, and control, in male South Asian
      immigrants in the United Arab Emirates: a cross-sectional study.
AB  - BACKGROUND: South Asian males constitute the largest proportion of the United
      Arab Emirates (UAE) population. Minimal data is available on the prevalence of
      hypertension among South Asian immigrants in the UAE. We determined the
      prevalence, associated factors, awareness, treatment, and control of hypertension
      among male South Asian immigrants from India, Pakistan and Bangladesh residing in
      the UAE. METHODS: We recruited a representative sample (n = 1375; 76.4 %
      participation rate) of South Asian adult (>=18 years) immigrant males, including
      Indian (n = 433), Pakistani (n = 383) and Bangladeshi (n = 559) nationalities in
      Al Ain, UAE (January-June 2012). Blood pressure, height, body mass, waist and hip
      circumference data were obtained using standard protocols. Information related to
      socio-demographics, lifestyle factors, history of diagnosis and treatment of
      hypertension was collected through a pilot-tested adapted version of the STEPS
      instrument, developed by the World Health Organization for the measurement of non
      communicable disease risk factors at the country level . RESULTS: Mean age of
      participants was 34.0 years (95 % confidence interval (CI): 33.4, 34.5 years) and
      the overall prevalence of hypertension was 30.5 % (95 % CI 28.0, 32.8). In this
      study, 62 % of study participants had never had their blood pressure measured.
      Over three quarters (76 %) of the sample classified as hypertensive were not
      aware of their condition. Less than half (48.5 %) of the sample that were aware
      of their hypertension reported using antihypertensive medication and only 8.3 %
      had their hypertension under control (<140/90 mmHg). Hypertensive participants
      were more likely to be overweight (adjusted odds ratio (AOR) = 1.43; 95 % CI
      1.01, 2.01); obese (AOR = 2.49; 95 % CI: 1.51, 4.10); have central obesity (AOR =
      2.01; 95 % CI 1.37, 2.92); have a family history of hypertension (AOR = 1.51; 95
      % CI 1.05, 2.17); and were less likely to walk 30 minutes daily (AOR = 1.79; 95 %
      CI 1.24, 2.60). CONCLUSIONS: The prevalence of hypertension in a representative
      sample of young male South Asian immigrants living in the UAE was relatively
      high. However, the awareness, treatment, and control of hypertension within this
      population were very low. Strategies are urgently needed to improve the awareness
      and control of hypertension in this large population of migrant workers in the
      UAE.

PMID- 25948546
TI  - A transgenic ginseng vaccine for bovine viral diarrhea.
AB  - BACKGROUND: Bovine viral diarrhea virus (BVDV) infections are endemic in cattle
      populations worldwide and cause major economic losses. Thus, an effective vaccine
      is needed against the transmission of BVDV. The glycoprotein E(rns) is one of the
      envelope proteins of this virus and shows BVDV-related immunogenicity. Here, we
      report the use of Panax ginseng as an alternative production platform for the
      expression of glycoprotein E(rns) via Agrobacterium-mediated transformation.
      RESULT: Polymerase chain reaction (PCR) and reverse transcription (RT)-PCR
      analyses showed that pBI121-E(rns) was stably integrated into the chromosome of
      transformants. ELISA assay and Western blot analysis confirmed the antigenicity
      of plant-derived E(rns) glycoprotein. Immunogenicity was evaluated subcutaneously
      in deer using a soluble protein extract of dried transgenic ginseng hairy roots.
      Specific humoral and cell-mediated immune responses against BVDV were detected
      following immunization. CONCLUSION: These results demonstrated that the E(rns)
      glycoprotein could be expressed in ginseng hairy roots and that plant-derived
      glycoprotein E(rns) retained its antigenicity and immunogenicity.

PMID- 25948544
TI  - Tarantula toxins use common surfaces for interacting with Kv and ASIC ion
      channels.
AB  - Tarantula toxins that bind to voltage-sensing domains of voltage-activated ion
      channels are thought to partition into the membrane and bind to the channel
      within the bilayer. While no structures of a voltage-sensor toxin bound to a
      channel have been solved, a structural homolog, psalmotoxin (PcTx1), was recently
      crystalized in complex with the extracellular domain of an acid sensing ion
      channel (ASIC). In the present study we use spectroscopic, biophysical and
      computational approaches to compare membrane interaction properties and channel
      binding surfaces of PcTx1 with the voltage-sensor toxin guangxitoxin (GxTx-1E).
      Our results show that both types of tarantula toxins interact with membranes, but
      that voltage-sensor toxins partition deeper into the bilayer. In addition, our
      results suggest that tarantula toxins have evolved a similar concave surface for
      clamping onto alpha-helices that is effective in aqueous or lipidic physical
      environments. 

PMID- 25948547
TI  - Thermally induced collision of droplets in an immiscible outer fluid.
AB  - Micro-total analysis systems (MUTAS) have attracted wide attention and are
      identified as a promising solution for sample transport, filtration, chemical
      reactions, separation and detection. Despite their popularity, the selection of
      an appropriate mechanism for droplet transport and coalescence has always been a
      challenge. This paper investigates the use of Marangoni flow as a mechanism for
      levitating and transporting droplets on immiscible liquid films at higher speeds
      than is possible currently. For the first time, we show that it is possible to
      realize the natural coalescence of droplets through Marangoni effect without any
      external stimulation, and deliver the coalesced droplet to a certain destination
      through the use of surface tension gradients. The effects of shape and size on
      collision outcome are studied. Regions of coalescence and stretching separation
      of colliding droplets are delineated based on Weber number and impact number. In
      addition, the effect of viscosity on post collision regimes is studied. The
      findings in this fundamental study can be beneficial to many applications such as
      welding, drug delivery and microfluidics devices in controlling small droplets
      and targeting them to various locations. 

PMID- 25948548
TI  - Recovery of the wild type atomic flexibility in the HIV-1 protease double
      mutants.
AB  - The emergence of drug resistant mutations due to the selective pressure exerted
      by antiretrovirals, including protease inhibitors (PIs), remains a major problem
      in the treatment of AIDS. During PIs therapy, the occurrence of primary mutations
      in the wild type HIV-1 protease reduces both the affinity for the inhibitors and
      the viral replicative capacity compared to the wild type (WT) protein, but
      additional mutations compensate for this reduced viral fitness. To investigate
      this phenomenon from the structural point of view, we combined Molecular Dynamics
      and Normal Mode Analysis to analyze and compare the variations of the flexibility
      of C-alpha atoms and the differences in hydrogen bond (h-bond) network between
      the WT and double mutants. In most cases, the flexibility profile of the double
      mutants was more often similar to that of the WT than to that of the related
      single base mutants. All single mutants showed a significant alteration in h-bond
      formation compared to WT. Most of the significant changes occur in the border
      between the flap and cantilever regions. We found that all the considered double
      mutants have their h-bond pattern significantly altered in comparison to the
      respective single base mutants affecting their flexibility profile that becomes
      more similar to that of WT. This WT flexibility restoration in the double mutants
      appears as an important factor for the HIV-1 fitness recovery observed in
      patients. 

PMID- 25948550
TI  - Positive Effects of a Sufficient Pre-fracture Serum Vitamin D Level on the Long
      Term Survival of Hip Fracture Patients in Finland: A Minimum 11-Year Follow-Up.
AB  - BACKGROUND: Several studies have shown that the mortality of elderly hip fracture
      patients is higher than that in the general population, and is higher in male
      than in female hip fracture patients. OBJECTIVE: The objective of this study was
      to investigate factors affecting overall mortality at a minimum of 11 years
      following a new hip fracture. METHODS: The sex, age, pre-fracture serum 25
      hydroxyvitamin D level, American Society of Anesthesiologists physical status
      classification (ASA class), 1- to 12-month mortality, and 2- to 11-year mortality
      of hip fracture patients were collected. The use of anti-osteoporotic medication
      and prescribed calcium and vitamin D supplements during the first 3 post
      operative years were checked. The survival of the patients was analyzed using
      both the Bayesian multivariate analysis and the life table method. RESULTS: The
      mean age of females at the time of the index hip fracture was 80.5 years and of
      males was 73 years. The protective factors were age <80 years; ASA class 1-2;
      serum 25-hydroxyvitamin level >= 50 nmol/L; post-fracture use of calcium and
      vitamin D supplementation; post-fracture concomitant use of calcium and vitamin D
      supplementation and anti-osteoporotic drugs; and male sex. The excess mortality
      was higher among women than men. Survival was highest among patients with a
      vitamin D level of >= 50 nmol/L. Post-fracture concomitant use of calcium and
      vitamin D and anti-osteoporotic drugs was positively associated with survival.
      CONCLUSION: Our results indicate a positive relationship between a sufficient pre
      fracture vitamin D serum concentration (>= 50 nmol/L) and survival, and a
      potential relationship between reduced mortality and the concomitant post
      fracture use of prescribed calcium plus vitamin D supplementation and anti
      osteoporotic medication.

PMID- 25948551
TI  - Targeting Heat-Shock Protein 90 (HSP90) as a Complementary Strategy to Immune
      Checkpoint Blockade for Cancer Therapy.
AB  - The demonstration that immune checkpoint blockade can meaningfully improve
      outcomes for cancer patients has revolutionized the field of immuno-oncology. New
      biologic agents targeting specific checkpoints have shown remarkable durability
      in terms of patient response and, importantly, exhibit clinical activity across a
      range of human malignancies, including many that have traditionally proven
      refractory to other immunotherapies. In this rapidly evolving area, a key
      consideration relates to the identification of novel combinatorial strategies
      that exploit existing or investigational cancer therapies in order to optimize
      patient outcomes and the proportion of individuals able to derive benefit from
      this approach. In this regard, heat-shock protein 90 (HSP90) represents an
      important emerging target for cancer therapy because its inactivation results in
      the simultaneous blockade of multiple signaling pathways and can sensitize tumor
      cells to other anticancer agents. Within the context of immunology, HSP90 plays a
      dual regulatory role, with its functional inhibition resulting in both
      immunosuppressive and immunostimulatory effects. In this Cancer Immunology at the
      Crossroads overview, the anticancer activity profile of targeted HSP90 inhibitors
      is discussed along with their paradoxical roles in immunology. Overall, we
      explore the rationale for combining the modalities of HSP90 inhibition and immune
      checkpoint blockade in order to augment the antitumor immune response in cancer.

PMID- 25948552
TI  - Impact of Child Maltreatment on Attachment and Social Rank Systems: Introducing
      an Integrated Theory.
AB  - Child maltreatment is a prevalent societal problem that has been linked to a wide
      range of social, psychological, and emotional difficulties. Maltreatment impacts
      on two putative evolved psychobiological systems in particular, the attachment
      system and the social rank system. The maltreatment may disrupt the child's
      ability to form trusting and reassuring relationships and also creates a power
      imbalance where the child may feel powerless and ashamed. The aim of the current
      article is to outline an evolutionary theory for understanding the impact of
      child maltreatment, focusing on the interaction between the attachment and the
      social rank system. We provide a narrative review of the relevant literature
      relating to child maltreatment and these two theories. This research highlights
      how, in instances of maltreatment, these ordinarily adaptive systems may become
      maladaptive and contribute to psychopathology. We identify a number of novel
      hypotheses that can be drawn from this theory, providing a guide for future
      research. We finally explore how this theory provides a guide for the treatment
      of victims of child maltreatment. In conclusion, the integrated theory provides a
      framework for understanding and predicting the consequences of maltreatment, but
      further research is required to test several hypotheses made by this theory. 

PMID- 25948549
TI  - Current pharmacological management of hypotensive syndromes in the elderly.
AB  - Hypotensive syndromes are common among older adults. Symptomatic drop in blood
      pressure with standing, eating and head turning is very common in older adults.
      These conditions cause significant morbidity like dizziness, syncope and falls as
      well as a resultant decrease in function. Blood pressure dysregulation due to
      autonomic function abnormalities plays a role in causing these conditions. Non
      pharmacological measures should be the first line of management, but it is not
      always sufficient for subjects with symptomatic hypotensive syndromes. Different
      medication groups have been shown to be useful. This article focuses mainly on
      the medication management of these conditions based on efficacy and tolerability
      evidence in the literature. Standard medication management recommendations based
      on evidence are lacking for many medications used in treating these hypotensive
      syndromes. 

PMID- 25948553
TI  - Src inhibitors modulate frataxin protein levels.
AB  - Defective expression of frataxin is responsible for the inherited, progressive
      degenerative disease Friedreich's Ataxia (FRDA). There is currently no effective
      approved treatment for FRDA and patients die prematurely. Defective frataxin
      expression causes critical metabolic changes, including redox imbalance and ATP
      deficiency. As these alterations are known to regulate the tyrosine kinase Src,
      we investigated whether Src might in turn affect frataxin expression. We found
      that frataxin can be phosphorylated by Src. Phosphorylation occurs primarily on
      Y118 and promotes frataxin ubiquitination, a signal for degradation. Accordingly,
      Src inhibitors induce accumulation of frataxin but are ineffective on a non
      phosphorylatable frataxin-Y118F mutant. Importantly, all the Src inhibitors
      tested, some of them already in the clinic, increase frataxin expression and
      rescue the aconitase defect in frataxin-deficient cells derived from FRDA
      patients. Thus, Src inhibitors emerge as a new class of drugs able to promote
      frataxin accumulation, suggesting their possible use as therapeutics in FRDA. 

PMID- 25948555
TI  - Colonic inflammation in a samoan immigrant with gastric lymphoma shown by
      positron emission tomography.

PMID- 25948554
TI  - Disruption of the lamin A and matrin-3 interaction by myopathic LMNA mutations.
AB  - The nuclear face of the nuclear membrane is enriched with the intermediate
      filament protein lamin A. Mutations in LMNA, the gene encoding lamin A, lead to a
      diverse set of inherited conditions including myopathies that affect both the
      heart and skeletal muscle. To gain insight about lamin A protein interactions,
      binding proteins associated with the tail of lamin A were characterized. Of 130
      nuclear proteins found associated with the lamin A tail, 17 (13%) were previously
      described lamin A binding partners. One protein not previously linked to lamin A,
      matrin-3, was selected for further study, because like LMNA mutations, matrin-3
      has also been implicated in inherited myopathy. Matrin-3 binds RNA and DNA and is
      a nucleoplasmic protein originally identified from the insoluble nuclear
      fraction, referred to as the nuclear matrix. Anti-matrin-3 antibodies were found
      to co-immunoprecipitate lamin A, and the lamin-A binding domain was mapped to the
      carboxy-terminal half of matrin-3. Three-dimensional mapping of the lamin A
      matrin-3 interface showed that the LMNA truncating mutation Delta303, which lacks
      the matrin-3 binding domain, was associated with an increased distance between
      lamin A and matrin-3. LMNA mutant cells are known to have altered biophysical
      properties and the matrin-3-lamin A interface is positioned to contribute to
      these defects. 

PMID- 25948556
TI  - Bakua: tinea imbricata in the solomon islands.

PMID- 25948557
TI  - A Rare Cause of Retropharyngeal Abscess: Cervical Pott's Disease.

PMID- 25948558
TI  - Ebola and cholera.

PMID- 25948559
TI  - Skin Scraping is the Most Accessible Technique for the Parasitological Diagnosis
      of American Tegumentary Leishmaniasis.

PMID- 25948560
TI  - In response.

PMID- 25948561
TI  - Errata.

PMID- 25948562
TI  - Nepal earthquake gives rise to fears over poor sanitation.

PMID- 25948564
TI  - Fine Mapping Causal Variants with an Approximate Bayesian Method Using Marginal
      Test Statistics.
AB  - Two recently developed fine-mapping methods, CAVIAR and PAINTOR, demonstrate
      better performance over other fine-mapping methods. They also have the advantage
      of using only the marginal test statistics and the correlation among SNPs. Both
      methods leverage the fact that the marginal test statistics asymptotically follow
      a multivariate normal distribution and are likelihood based. However, their
      relationship with Bayesian fine mapping, such as BIMBAM, is not clear. In this
      study, we first show that CAVIAR and BIMBAM are actually approximately equivalent
      to each other. This leads to a fine-mapping method using marginal test statistics
      in the Bayesian framework, which we call CAVIAR Bayes factor (CAVIARBF). Another
      advantage of the Bayesian framework is that it can answer both association and
      fine-mapping questions. We also used simulations to compare CAVIARBF with other
      methods under different numbers of causal variants. The results showed that both
      CAVIARBF and BIMBAM have better performance than PAINTOR and other methods.
      Compared to BIMBAM, CAVIARBF has the advantage of using only marginal test
      statistics and takes about one-quarter to one-fifth of the running time. We
      applied different methods on two independent cohorts of the same phenotype.
      Results showed that CAVIARBF, BIMBAM, and PAINTOR selected the same top 3 SNPs;
      however, CAVIARBF and BIMBAM had better consistency in selecting the top 10
      ranked SNPs between the two cohorts. Software is available at
      https://bitbucket.org/Wenan/caviarbf.

PMID- 25948563
TI  - Evaluation of Ancestral Sequence Reconstruction Methods to Infer Nonstationary
      Patterns of Nucleotide Substitution.
AB  - Inference of gene sequences in ancestral species has been widely used to test
      hypotheses concerning the process of molecular sequence evolution. However, the
      approach may produce spurious results, mainly because using the single best
      reconstruction while ignoring the suboptimal ones creates systematic biases. Here
      we implement methods to correct for such biases and use computer simulation to
      evaluate their performance when the substitution process is nonstationary. The
      methods we evaluated include parsimony and likelihood using the single best
      reconstruction (SBR), averaging over reconstructions weighted by the posterior
      probabilities (AWP), and a new method called expected Markov counting (EMC) that
      produces maximum-likelihood estimates of substitution counts for any branch under
      a nonstationary Markov model. We simulated base composition evolution on a
      phylogeny for six species, with different selective pressures on G+C content
      among lineages, and compared the counts of nucleotide substitutions recorded
      during simulation with the inference by different methods. We found that large
      systematic biases resulted from (i) the use of parsimony or likelihood with SBR,
      (ii) the use of a stationary model when the substitution process is
      nonstationary, and (iii) the use of the Hasegawa-Kishino-Yano (HKY) model, which
      is too simple to adequately describe the substitution process. The nonstationary
      general time reversible (GTR) model, used with AWP or EMC, accurately recovered
      the substitution counts, even in cases of complex parameter fluctuations. We
      discuss model complexity and the compromise between bias and variance and suggest
      that the new methods may be useful for studying complex patterns of nucleotide
      substitution in large genomic data sets.

PMID- 25948565
TI  - Functional coupling constrains craniofacial diversification in Lake Tanganyika
      cichlids.
AB  - Functional coupling, where a single morphological trait performs multiple
      functions, is a universal feature of organismal design. Theory suggests that
      functional coupling may constrain the rate of phenotypic evolution, yet empirical
      tests of this hypothesis are rare. In fish, the evolutionary transition from
      guarding the eggs on a sandy/rocky substrate (i.e. substrate guarding) to
      mouthbrooding introduces a novel function to the craniofacial system and offers
      an ideal opportunity to test the functional coupling hypothesis. Using a
      combination of geometric morphometrics and a recently developed phylogenetic
      comparative method, we found that head morphology evolution was 43% faster in
      substrate guarding species than in mouthbrooding species. Furthermore, for
      species in which females were solely responsible for mouthbrooding the males had
      a higher rate of head morphology evolution than in those with bi-parental
      mouthbrooding. Our results support the hypothesis that adaptations resulting in
      functional coupling constrain phenotypic evolution. 

PMID- 25948566
TI  - Odour cues from suitors' nests determine mating success in a fish.
AB  - Animals use a range of sensory cues for finding food, avoiding predators and
      choosing mates. In this regard, the aquatic environment is particularly suitable
      for the use of olfactory and other chemical cues. Nevertheless, mate choice
      research, even on aquatic organisms, has focused on visual signals, while
      chemical cues relevant in sexual selection have been assumed to be 'intrinsic'
      excretions of mate candidates. Here, using the sand goby Pomatoschistus minutus,
      a small fish with paternal egg care, we investigated the possibility that
      'extrinsic' chemical cues in the males' nests could also have a significant
      contribution to mating success. We found that females strongly avoided laying
      eggs into nests subject to the odour of Saprolegnia water moulds (an egg
      infection) and that this effect was independent of the females' initial, visually
      based preference for males. To the best of our knowledge, this is the first study
      to show that chemical cues related to parental failure can play a large role in
      sexual selection. 

PMID- 25948567
TI  - Double trouble: combined action of meiotic drive and Wolbachia feminization in
      Eurema butterflies.
AB  - Arthropod sex ratios can be manipulated by a diverse range of selfish genetic
      elements, including maternally inherited Wolbachia bacteria. Feminization by
      Wolbachia is rare but has been described for Eurema mandarina butterflies. In
      this species, some phenotypic and functional females, thought to be ZZ genetic
      males, are infected with a feminizing Wolbachia strain, wFem. Meanwhile,
      heterogametic WZ females are not infected with wFem. Here, we establish a
      quantitative PCR assay allowing reliable sexing in three Eurema species. Against
      expectation, all E. mandarina females, including wFem females, had only one Z
      chromosome that was paternally inherited. Observation of somatic interphase
      nuclei confirmed that W chromatin was absent in wFem females, but present in
      females without wFem. We conclude that the sex bias in wFem lines is due to
      meiotic drive (MD) that excludes the maternal Z and thus prevents formation of ZZ
      males. Furthermore, wFem lines may have lost the W chromosome or harbour a
      dysfunctional version, yet rely on wFem for female development; removal of wFem
      results in all-male offspring. This is the first study that demonstrates an
      interaction between MD and Wolbachia feminization, and it highlights
      endosymbionts as potentially confounding factors in MD of sex chromosomes. 

PMID- 25948568
TI  - Molecular evolution of the hyaluronan synthase 2 gene in mammals: implications
      for adaptations to the subterranean niche and cancer resistance.
AB  - The naked mole-rat (NMR) Heterocephalus glaber is a unique and fascinating mammal
      exhibiting many unusual adaptations to a subterranean lifestyle. The recent
      discovery of their resistance to cancer and exceptional longevity has opened up
      new and important avenues of research. Part of this resistance to cancer has been
      attributed to the fact that NMRs produce a modified form of hyaluronan--a key
      constituent of the extracellular matrix--that is thought to confer increased
      elasticity of the skin as an adaptation for living in narrow tunnels. This so
      called high molecular mass hyaluronan (HMM-HA) stems from two apparently unique
      substitutions in the hyaluronan synthase 2 enzyme (HAS2). To test whether other
      subterranean mammals with similar selection pressures also show molecular
      adaptation in their HAS2 gene, we sequenced the HAS2 gene for 11 subterranean
      mammals and closely related species, and combined these with data from 57 other
      mammals. Comparative screening revealed that one of the two putatively important
      HAS2 substitutions in the NMR predicted to have a significant effect on
      hyaluronan synthase function was uniquely shared by all African mole-rats.
      Interestingly, we also identified multiple other amino acid substitutions in key
      domains of the HAS2 molecule, although the biological consequences of these for
      hyaluronan synthesis remain to be determined. Despite these results, we found
      evidence of strong purifying selection acting on the HAS2 gene across all
      mammals, and the NMR remains unique in its particular HAS2 sequence. Our results
      indicate that more work is needed to determine whether the apparent cancer
      resistance seen in NMR is shared by other members of the African mole-rat clade.

PMID- 25948570
TI  - Antioxidants safeguard telomeres in bold chicks.
AB  - Telomeres are sensitive to damage induced by oxidative stress, and thus it is
      expected that dietary antioxidants may support the maintenance of telomere length
      in animals, particularly those with a fast rate of life (e.g. fast metabolism,
      activity and growth). We tested experimentally the effect of antioxidant
      supplements on telomere length during early development in wild gull chicks with
      natural individual variations in behaviour pattern and growth rate. Proactive
      chicks had shorter telomeres than reactive chicks, but the penalty for the bold
      behaviour pattern was reduced by antioxidant supplementation. Chicks growing
      faster had longer telomeres during early growth, suggesting that inherited
      quality supports a fast life history. 

PMID- 25948569
TI  - Priority effects in a planktonic bloom-forming marine diatom.
AB  - Priority effects occur when a species or genotype with earlier arrival has an
      advantage such that its relative abundance in the community or population is
      increased compared with later-arriving species. Few studies have dealt with this
      concept in the context of within-species competition. Skeletonema marinoi is a
      marine diatom that shows a high degree of genetic differentiation between
      populations over small geographical distances. To test whether historical events
      such as priority effects may have been important in inducing these patterns of
      population differentiation, we performed microcosm experiments with successive
      inoculation of different S. marinoi strains. Our results show that even in the
      absence of a numerical advantage, significant priority effects were evident. We
      propose that priority effects may be an important mechanism in initiating
      population genetic differentiation. 

PMID- 25948571
TI  - Low genetic diversity in pygmy blue whales is due to climate-induced
      diversification rather than anthropogenic impacts.
AB  - Unusually low genetic diversity can be a warning of an urgent need to mitigate
      causative anthropogenic activities. However, current low levels of genetic
      diversity in a population could also be due to natural historical events,
      including recent evolutionary divergence, or long-term persistence at a small
      population size. Here, we determine whether the relatively low genetic diversity
      of pygmy blue whales (Balaenoptera musculus brevicauda) in Australia is due to
      natural causes or overexploitation. We apply recently developed analytical
      approaches in the largest genetic dataset ever compiled to study blue whales (297
      samples collected after whaling and representing lineages from Australia,
      Antarctica and Chile). We find that low levels of genetic diversity in Australia
      are due to a natural founder event from Antarctic blue whales (Balaenoptera
      musculus intermedia) that occurred around the Last Glacial Maximum, followed by
      evolutionary divergence. Historical climate change has therefore driven the
      evolution of blue whales into genetically, phenotypically and behaviourally
      distinct lineages that will likely be influenced by future climate change. 

PMID- 25948572
TI  - The last diadectomorph sheds light on Late Palaeozoic tetrapod biogeography.
AB  - Diadectomorpha is a clade of Late Palaeozoic vertebrates widely recognized as the
      sister group of crown-group Amniota and the first tetrapod lineage to evolve high
      fibre herbivory. Despite their evolutionary importance, diadectomorphs are
      restricted stratigraphically and geographically, with all records being from the
      Upper Carboniferous and Lower Permian of North America and Germany. We describe a
      new diadectomorph, Alveusdectes fenestralis, based on a partial skull from the
      Upper Permian of China. The new species exhibits the derived mechanism for
      herbivory and is recovered phylogenetically as a deeply nested diadectid.
      Approximately 16 Myr younger than any other diadectomorph, Alveusdectes is the
      product of at least a 46 Myr ghost lineage. How much of this time was probably
      spent in Russia and/or central Asia will remain unclear until a specimen is
      described that subdivides this cryptic history, but the lineage assuredly crossed
      this region before entering the relatively isolated continent of North China. The
      discovery of Alveusdectes raises important questions regarding diadectomorph
      extinction dynamics including what, if any, ecological factors limited the
      diversity of this group in eastern Pangea. It also suggests that increased
      sampling in Asia will likely significantly affect our views of clade and faunal
      insularity leading up to the Permo-Triassic extinction. 

PMID- 25948573
TI  - Thyroid autoimmunity, hypothyroidism and ovarian reserve: a cross-sectional study
      of 5000 women based on age-specific AMH values.
AB  - STUDY QUESTION: Is there any association between thyroid autoimmunity (TAI) and
      diminished ovarian reserve (DOR)? SUMMARY ANSWER: TAI and hypothyroidism are not
      associated with low ovarian reserve. WHAT IS KNOWN ALREADY: TAI is a common co
      existent endocrinopathy in women with primary ovarian insufficiency. Several
      studies support a potential link between TAI and the reduction in ovarian
      reserve. However, robust evidence regarding its prevalence in women with DOR is
      lacking. STUDY DESIGN, SIZE, DURATION: This study is a large cross-sectional
      analysis of retrospective data from the Centre for Reproductive
      Medicine/University Hospital of Brussels. Serum measurements were taken for anti
      Mullerian hormone (AMH), free thyroxine (FT4), thyroid-stimulating hormone (TSH)
      and anti-thyroperoxidase (anti-TPO). PARTICIPANTS/MATERIALS, SETTING, METHODS:
      Among 5076 consecutive women, 4894 women had their AMH, FT4, TSH and anti-TPO
      levels measured on the same day. AMH levels were plotted in relation to age for
      the whole patients' cohort and age-specific AMH values (per year) were considered
      in order to categorize women according to the AMH levels of ovarian reserve.
      There were 3929 women who demonstrated normal reserve, 487 women who had low
      ovarian reserve and 478 women who demonstrated high ovarian reserve. MAIN RESULTS
      AND THE ROLE OF CHANCE: Serum FT4 and TSH levels were comparable between
      different ovarian reserve categories (P = 0.611 and 0.811, respectively). No
      significant differences were observed in the prevalence of positive anti-TPO
      antibodies among women with low (12.1%), normal (10.3%) and high (9.8%) ovarian
      reserve (P = 0.423). Finally, the prevalence of overt or subclinical
      hypothyroidism was comparable between the groups (4.1% in low, 4.6% in normal and
      3.8% in high ovarian reserve women, P = 0.645).Analysis according to the exact
      cause of low ovarian reserve demonstrated that women with a genetic cause of low
      ovarian reserve had a significantly higher prevalence of overt hypothyroidism and
      subclinical hypothyroidism compared with women with unexplained low ovarian
      reserve for their age (25 versus 3.2%, P = 0.002 and 18.8 versus 1.6%, P = 0.004,
      respectively). On the contrary, no significant differences were observed in the
      prevalence of hypothyroidism between genetic causes and iatrogenic causes (P =
      0.316) and between iatrogenic and unexplained causes (P = 0.219) of low ovarian
      reserve. LIMITATIONS, REASONS FOR CAUTION: This is a cross-sectional analysis
      based on retrospective data collection. Due to the retrospective design of this
      study, the presence of biases related to such a study design cannot be excluded.
      Furthermore, this study assessed only the association of TAI, and not
      autoimmunity in general, with ovarian reserve. WIDER IMPLICATIONS OF THE
      FINDINGS: TAI and hypothyroidism are not associated with low ovarian reserve.
      Future research should focus on examining underlying mechanisms, other than TAI,
      which may have an effect on ovarian reserve. STUDY FUNDING/COMPETING INTERESTS:
      No external funding was used for this study. No conflicts of interest are
      declared.

PMID- 25948574
TI  - Ebola: a game changer for vaccines, or a scare that will soon be forgotten?

PMID- 25948575
TI  - The use of an anti-fibrinolytic agent to reduce endoleak following endovascular
      repair of multiple aortic aneurysms.
AB  - This paper reports on the therapeutic use of tranexamic acid in an elderly
      patient with severe comorbidities that precluded even endovascular
      reintervention. Orally administered tranexamic acid mitigated and partially
      reversed two and a half years of progressive aneurysmal expansion and closed a
      persistent endoleak after thoracic endovascular aneurysm repair and endovascular
      aneurysm repair for coexisting lesions. Reappearance of the endoleak when
      tranexamic acid was accidentally stopped and its re-closure after the resumption
      of tranexamic acid treatment confirmed causality. This singular experience
      extends prior published observations that administration of prophylactic
      tranexamic acid before thoracic endovascular aneurysm repair and endovascular
      aneurysm repair resulted in significantly greater shrinkage, particularly if an
      endoleak or coagulopathy was present. 

PMID- 25948576
TI  - Parental Leave Policies and Pediatric Trainees in the United States.
AB  - BACKGROUND: The American Academy of Pediatrics (AAP) states that each residency
      program should have a clearly delineated, written policy for parental leave.
      Parental leave has important implications for trainees' ability to achieve their
      breastfeeding goals. OBJECTIVE: This study aimed to measure the knowledge and
      awareness among members of the AAP Section on Medical Students, Residents, and
      Fellowship Trainees (SOMSRFT) regarding parental leave. METHODS: An online survey
      was emailed to SOMSRFT members in June 2013. Quantitative data are presented as
      percentage of respondents. Awareness of leave policies was analyzed based on
      having children and the sex of respondents. RESULTS: Nine hundred twenty-seven
      members responded to the survey. Among those with children, 40% needed to extend
      the duration of their training in order to have longer maternity leave, 44% of
      whom did so in order to breastfeed longer. Thirty percent of respondents did not
      know if their program had a written, accessible policy for parental leave.
      Trainees without children and men were more unaware of specific aspects of
      parental leave such as eligibility for the Family Medical Leave Act as compared
      to women and those with children. CONCLUSION: Despite the fact that United States
      national policies support parental leave during pediatrics training, and a
      majority of programs comply, trainees' awareness regarding these policies needs
      improvement.

PMID- 25948577
TI  - Narcolepsy Treated with Racemic Amphetamine during Pregnancy and Breastfeeding.
AB  - This case report describes a woman with narcolepsy treated with racemic
      amphetamine (rac-amphetamine) during pregnancy and breastfeeding with follow-up
      on the infant's development up to 10 months of age. The pregnancy outcome and the
      pharmacokinetics of rac-amphetamine were studied during breastfeeding. The
      pregnancy and the delivery were uneventful. Concentrations of rac-amphetamine
      were determined in the plasma of the mother and infant, and in the breast milk
      with a liquid chromatography-mass spectrometry method. Samples were obtained at
      2, 5, and 9 weeks postpartum. The transfer of rac-amphetamine to the breast milk
      was extensive (mean milk/maternal plasma concentration ratio approximately 3).
      The breastfed infant had a low plasma concentration of rac-amphetamine (about 9%
      of the maternal plasma level) and the calculated relative infant dose was low
      (2%). No adverse effects were observed in the breastfed infant. The infant's
      somatic and psychomotor development up to 10 months of age was normal. Further
      studies of amphetamine prescribed for medical reasons during pregnancy and
      lactation are needed. 

PMID- 25948578
TI  - Metagenomic Analysis of Milk of Healthy and Mastitis-Suffering Women.
AB  - BACKGROUND: Some studies have been conducted to assess the composition of the
      bacterial communities inhabiting human milk, but they did not evaluate the
      presence of other microorganisms, such as fungi, archaea, protozoa, or viruses.
      OBJECTIVE: This study aimed to compare the metagenome of human milk samples
      provided by healthy and mastitis-suffering women. METHODS: DNA was isolated from
      human milk samples collected from 10 healthy women and 10 women with symptoms of
      lactational mastitis. Shotgun libraries from total extracted DNA were constructed
      and the libraries were sequenced by 454 pyrosequencing. RESULTS: The amount of
      human DNA sequences was >= 90% in all the samples. Among the bacterial sequences,
      the predominant phyla were Proteobacteria, Firmicutes, and Bacteroidetes. The
      healthy core microbiome included the genera Staphylococcus, Streptococcus,
      Bacteroides, Faecalibacterium, Ruminococcus, Lactobacillus, and
      Propionibacterium. At the species level, a high degree of inter-individual
      variability was observed among healthy women. In contrast, Staphylococcus aureus
      clearly dominated the microbiome in the samples from the women with acute
      mastitis whereas high increases in Staphylococcus epidermidis-related reads were
      observed in the milk of those suffering from subacute mastitis. Fungal and
      protozoa-related reads were identified in most of the samples, whereas Archaea
      reads were absent in samples from women with mastitis. Some viral-related
      sequence reads were also detected. CONCLUSION: Human milk contains a complex
      microbial metagenome constituted by the genomes of bacteria, archaea, viruses,
      fungi, and protozoa. In mastitis cases, the milk microbiome reflects a loss of
      bacterial diversity and a high increase of the sequences related to the
      presumptive etiological agents.

PMID- 25948579
TI  - antiSMASH 3.0-a comprehensive resource for the genome mining of biosynthetic gene
      clusters.
AB  - Microbial secondary metabolism constitutes a rich source of antibiotics,
      chemotherapeutics, insecticides and other high-value chemicals. Genome mining of
      gene clusters that encode the biosynthetic pathways for these metabolites has
      become a key methodology for novel compound discovery. In 2011, we introduced
      antiSMASH, a web server and stand-alone tool for the automatic genomic
      identification and analysis of biosynthetic gene clusters, available at
      http://antismash.secondarymetabolites.org. Here, we present version 3.0 of
      antiSMASH, which has undergone major improvements. A full integration of the
      recently published ClusterFinder algorithm now allows using this probabilistic
      algorithm to detect putative gene clusters of unknown types. Also, a new
      dereplication variant of the ClusterBlast module now identifies similarities of
      identified clusters to any of 1172 clusters with known end products. At the
      enzyme level, active sites of key biosynthetic enzymes are now pinpointed through
      a curated pattern-matching procedure and Enzyme Commission numbers are assigned
      to functionally classify all enzyme-coding genes. Additionally, chemical
      structure prediction has been improved by incorporating polyketide reduction
      states. Finally, in order for users to be able to organize and analyze multiple
      antiSMASH outputs in a private setting, a new XML output module allows offline
      editing of antiSMASH annotations within the Geneious software. 

PMID- 25948580
TI  - PACCMIT/PACCMIT-CDS: identifying microRNA targets in 3' UTRs and coding
      sequences.
AB  - The purpose of the proposed web server, publicly available at
      http://paccmit.epfl.ch, is to provide a user-friendly interface to two algorithms
      for predicting messenger RNA (mRNA) molecules regulated by microRNAs: (i) PACCMIT
      (Prediction of ACcessible and/or Conserved MIcroRNA Targets), which identifies
      primarily mRNA transcripts targeted in their 3' untranslated regions (3' UTRs),
      and (ii) PACCMIT-CDS, designed to find mRNAs targeted within their coding
      sequences (CDSs). While PACCMIT belongs among the accurate algorithms for
      predicting conserved microRNA targets in the 3' UTRs, the main contribution of
      the web server is 2-fold: PACCMIT provides an accurate tool for predicting
      targets also of weakly conserved or non-conserved microRNAs, whereas PACCMIT-CDS
      addresses the lack of similar portals adapted specifically for targets in CDS.
      The web server asks the user for microRNAs and mRNAs to be analyzed, accesses the
      precomputed P-values for all microRNA-mRNA pairs from a database for all mRNAs
      and microRNAs in a given species, ranks the predicted microRNA-mRNA pairs,
      evaluates their significance according to the false discovery rate and finally
      displays the predictions in a tabular form. The results are also available for
      download in several standard formats. 

PMID- 25948581
TI  - CDK-mediated RNF4 phosphorylation regulates homologous recombination in S-phase.
AB  - There are the two major pathways responsible for the repair of DNA double-strand
      breaks (DSBs): non-homologous end-joining (NHEJ) and homologous recombination
      (HR). NHEJ operates throughout the cell-cycle, while HR is primarily active in
      the S/G2 phases suggesting that there are cell cycle-specific mechanisms that
      regulate the balance between NHEJ and HR. Here we reported that CDK2 could
      phosphorylate RNF4 on T26 and T112 and enhance RNF4 E3 ligase activity, which is
      important for MDC1 degradation and proper HR repair during S phase. Mutation of
      the RNF4 phosphorylation sites results in MDC1 stabilization, which in turn
      compromised HR during S-phase. These results suggest that in addition to drive
      cell cycle progression, CDK also targets RNF4, which is involved in the
      regulatory network of DSBs repair. 

PMID- 25948582
TI  - HAT3-mediated acetylation of PCNA precedes PCNA monoubiquitination following
      exposure to UV radiation in Leishmania donovani.
AB  - Histone modifications impact various processes. In examining histone
      acetyltranferase HAT3 of Leishmania donovani, we find elimination of HAT3 causes
      decreased cell viability due to defects in histone deposition, and aberrant cell
      cycle progression pattern. HAT3 associates with proliferating cell nuclear
      antigen (PCNA), helping load PCNA onto chromatin in proliferating cells. HAT3
      nulls show heightened sensitivity to UV radiation. Following UV exposure, PCNA
      cycles off/on chromatin only in cells expressing HAT3. Inhibition of the
      ubiquitin-proteasome pathway prior to UV exposure allows accumulation of
      chromatin-bound PCNA, and reveals that HAT3-nulls are deficient in PCNA
      monoubiquitination as well as polyubiquitination. While poor monoubiquitination
      of PCNA may adversely affect translesion DNA synthesis-based repair processes,
      polyubiquitination deficiencies may result in continued retention of chromatin
      bound PCNA, leading to genomic instability. On suppressing the proteasome pathway
      we also find that HAT3 mediates PCNA acetylation in response to UV. HAT3-mediated
      PCNA acetylation may serve as a flag for PCNA ubiquitination, thus aiding DNA
      repair. While PCNA acetylation has previously been linked to its degradation
      following UV exposure, this is the first report linking a HAT-mediated PCNA
      acetylation to PCNA monoubiquitination. These findings add a new dimension to our
      knowledge of the mechanisms regulating PCNA ubiquitination post-UV exposure in
      eukaryotes. 

PMID- 25948583
TI  - SELPHI: correlation-based identification of kinase-associated networks from
      global phospho-proteomics data sets.
AB  - While phospho-proteomics studies have shed light on the dynamics of cellular
      signaling, they mainly describe global effects and rarely explore mechanistic
      details, such as kinase/substrate relationships. Tools and databases, such as
      NetworKIN and PhosphoSitePlus, provide valuable regulatory details on signaling
      networks but rely on prior knowledge. They therefore provide limited information
      on less studied kinases and fewer unexpected relationships given that better
      studied signaling events can mask condition- or cell-specific 'network wiring'.
      SELPHI is a web-based tool providing in-depth analysis of phospho-proteomics data
      that is intuitive and accessible to non-bioinformatics experts. It uses
      correlation analysis of phospho-sites to extract kinase/phosphatase and phospho
      peptide associations, and highlights the potential flow of signaling in the
      system under study. We illustrate SELPHI via analysis of phospho-proteomics data
      acquired in the presence of erlotinib-a tyrosine kinase inhibitor (TKI)-in cancer
      cells expressing TKI-resistant and -sensitive variants of the Epidermal Growth
      Factor Receptor. In this data set, SELPHI revealed information overlooked by the
      reporting study, including the known role of MET and EPHA2 kinases in conferring
      resistance to erlotinib in TKI sensitive strains. SELPHI can significantly
      enhance the analysis of phospho-proteomics data contributing to improved
      understanding of sample-specific signaling networks. SELPHI is freely available
      via http://llama.mshri.on.ca/SELPHI.

PMID- 25948585
TI  - Mecp2 regulates neural cell differentiation by suppressing the Id1 to Her2 axis
      in zebrafish.
AB  - Rett syndrome (RTT) is a progressive neurological disorder caused by mutations in
      the X-linked protein methyl-CpG-binding protein 2 (MeCP2). The endogenous
      function of MeCP2 during neural differentiation is still unclear. Here, we report
      that mecp2 is required for brain development in zebrafish. Mecp2 was broadly
      expressed initially in embryos and enriched later in the brain. Either morpholino
      knockdown or genetic depletion of mecp2 inhibited neuronal differentiation,
      whereas its overexpression promoted neuronal differentiation, suggesting an
      essential role of mecp2 in directing neural precursors into differentiated
      neurons. Mechanistically, her2 (the zebrafish ortholog of mammalian Hes5) was
      upregulated in mecp2 morphants in an Id1-dependent manner. Moreover, knockdown of
      either her2 or id1 fully rescued neuronal differentiation in mecp2 morphants.
      These results suggest that Mecp2 plays an important role in neural cell
      development by suppressing the Id1-Her2 axis, and provide new evidence that
      embryonic neural defects contribute to the later motor and cognitive dysfunctions
      in RTT. 

PMID- 25948584
TI  - Claudin-4 is required for modulation of paracellular permeability by muscarinic
      acetylcholine receptor in epithelial cells.
AB  - The epithelial cholinergic system plays an important role in water, ion and
      solute transport. Previous studies have shown that activation of muscarinic
      acetylcholine receptors (mAChRs) regulates paracellular transport of epithelial
      cells; however, the underlying mechanism is still largely unknown. Here, we found
      that mAChR activation by carbachol and cevimeline reduced the transepithelial
      electrical resistance (TER) and increased the permeability of paracellular
      tracers in rat salivary epithelial SMG-C6 cells. Carbachol induced downregulation
      and redistribution of claudin-4, but not occludin or ZO-1 (also known as TJP1).
      Small hairpin RNA (shRNA)-mediated claudin-4 knockdown suppressed, whereas
      claudin-4 overexpression retained, the TER response to carbachol.
      Mechanistically, the mAChR-modulated claudin-4 properties and paracellular
      permeability were triggered by claudin-4 phosphorylation through ERK1/2 (also
      known as MAPK3 and MAPK1, respectively). Mutagenesis assay demonstrated that
      S195, but not S199, S203 or S207, of claudin-4, was the target for carbachol.
      Subsequently, the phosphorylated claudin-4 interacted with beta-arrestin2 and
      triggered claudin-4 internalization through the clathrin-dependent pathway. The
      internalized claudin-4 was further degraded by ubiquitylation. Taken together,
      these findings suggested that claudin-4 is required for mAChR-modulated
      paracellular permeability of epithelial cells through an ERK1/2, beta-arrestin2,
      clathrin and ubiquitin-dependent signaling pathway. 

PMID- 25948586
TI  - JNK2 controls fragmentation of the Golgi complex and the G2/M transition through
      phosphorylation of GRASP65.
AB  - In mammalian cells, the Golgi complex is composed of stacks that are connected by
      membranous tubules. During G2, the Golgi complex is disassembled into isolated
      stacks. This process is required for entry into mitosis, indicating that the
      correct inheritance of the organelle is monitored by a 'Golgi mitotic
      checkpoint'. However, the regulation and the molecular mechanisms underlying this
      Golgi disassembly are still poorly understood. Here, we show that JNK2 has a
      crucial role in the G2-specific separation of the Golgi stacks through
      phosphorylation of Ser277 of the Golgi-stacking protein GRASP65 (also known as
      GORASP1). Inhibition of JNK2 by RNA interference or by treatment with three
      unrelated JNK inhibitors causes a potent and persistent cell cycle block in G2.
      JNK activity becomes dispensable for mitotic entry if the Golgi complex is
      disassembled by brefeldin A treatment or by GRASP65 depletion. Finally,
      measurement of the Golgi fluorescence recovery after photobleaching demonstrates
      that JNK is required for the cleavage of the tubules connecting Golgi stacks. Our
      findings reveal that a JNK2-GRASP65 signalling axis has a crucial role in
      coupling Golgi inheritance and G2/M transition. 

PMID- 25948587
TI  - Patrick Morrison: An aspiring lumberjack.

PMID- 25948588
TI  - A Novel Cinnamon-Related Natural Product with Pim-1 Inhibitory Activity Inhibits
      Leukemia and Skin Cancer.
AB  - The Pim-1 kinase regulates cell survival, proliferation, and differentiation and
      is overexpressed frequently in many malignancies, including leukemia and skin
      cancer. In this study, we used kinase profiling analysis to demonstrate that 2'
      hydroxycinnamicaldehyde (2'-HCA), a compound found in cinnamon, specifically
      inhibits Pim-1 activity. Cocrystallography studies determined the hydrogen
      bonding pattern between 2'-HCA and Pim-1. Notably, 2'-HCA binding altered the apo
      kinase structure in a manner that shielded the ligand from solvent, thereby
      acting as a gatekeeper loop. Biologically, 2'-HCA inhibited the growth of human
      erythroleukemia or squamous epidermoid carcinoma cells by inducing apoptosis. The
      compound was also effective as a chemopreventive agent against EGF-mediated
      neoplastic transformation. Finally, 2'-HCA potently suppressed the growth of
      mouse xenografts representing human leukemia or skin cancer. Overall, our results
      offered preclinical proof of concept for 2'-HCA as a potent anticancer principle
      arising from direct targeting of the Pim-1 kinase.

PMID- 25948589
TI  - Tracking and Functional Characterization of Epithelial-Mesenchymal Transition and
      Mesenchymal Tumor Cells during Prostate Cancer Metastasis.
AB  - The epithelial-mesenchymal transition (EMT) has been postulated as a mechanism by
      which cancer cells acquire the invasive and stem-like traits necessary for
      distant metastasis. However, direct in vivo evidence for the role of EMT in the
      formation of cancer stem-like cells (CSC) and the metastatic cascade remains
      lacking. Here we report the first isolation and characterization of mesenchymal
      like and EMT tumor cells, which harbor both epithelial and mesenchymal
      characteristics, in an autochthonous murine model of prostate cancer. By crossing
      the established Pb-Cre(+/-);Pten(L/L);Kras(G12D) (/+) prostate cancer model with
      a vimentin-GFP reporter strain, generating CPKV mice, we were able to isolate
      epithelial, EMT, and mesenchymal-like cancer cells based on expression of
      vimentin and EpCAM. CPKV mice (but not mice with Pten deletion alone) exhibited
      expansion of cells with EMT (EpCAM(+)/Vim-GFP(+)) and mesenchymal-like (EpCAM(
      )/Vim-GFP(+)) characteristics at the primary tumor site and in circulation. These
      EMT and mesenchymal-like tumor cells displayed enhanced stemness and invasive
      character compared with epithelial tumor cells. Moreover, they displayed an
      enriched tumor-initiating capacity and could regenerate epithelial glandular
      structures in vivo, indicative of epithelia-mesenchyme plasticity. Interestingly,
      while mesenchymal-like tumor cells could persist in circulation and survive in
      the lung following intravenous injection, only epithelial and EMT tumor cells
      could form macrometastases. Our work extends the evidence that mesenchymal and
      epithelial states in cancer cells contribute differentially to their capacities
      for tumor initiation and metastatic seeding, respectively, and that EMT tumor
      cells exist with plasticity that can contribute to multiple stages of the
      metastatic cascade.

PMID- 25948590
TI  - Correction: Identification of Pax5 as a Target of MTA1 in B-cell Lymphomas.

PMID- 25948591
TI  - Correction: Metastasis-Associated Protein 1 Transgenic Mice: A New Model of
      Spontaneous B-cell Lymphomas.

PMID- 25948592
TI  - The Trevo XP 3*20 mm retriever ('Baby Trevo') for the treatment of distal
      intracranial occlusions.
AB  - OBJECTIVE: To report our single-center initial experience using the Trevo XP
      ProVue Retriever 3*20 mm ('Baby Trevo') for distal intracranial occlusions.
      METHODS: We performed a retrospective review of our interventional database for
      consecutive patients who underwent treatment for acute ischemic stroke with the
      Baby Trevo device between February and December 2014. RESULTS: Of 134 patients
      treated during the study period, 8 underwent treatment with the Baby Trevo for
      distal occlusions. Their mean age was 51+/-20 years, 5 (62.5%) were male, mean
      baseline National Institutes of Health Stroke Scale was 19+/-5. The mean interval
      between the time the patient was last-known normal to groin puncture was 527+/
      285 min, and the overall procedural length was 110+/-26 min. Intra-arterial
      tissue plasminogen activator was used in 5 (62.5%) cases. The device was used for
      a total of 10 branches: five middle cerebral artery (four superior M3 and one
      inferior M3), three anterior cerebral arteries (two pericallosal and one
      callosomarginal), and two posterior cerebral arteries (one P2 and one P3)
      occlusions. All patients achieved complete recanalization of the artery targeted
      by the Baby Trevo (arterial occlusive lesion 3). Good capillary reperfusion (TICI
      2b-3) was noted in 6 (75%) cases. One pass was performed in 7 vessels and 2
      passes in three branches. Vasospasm was noted in 5 (62.5%) of the vessels and
      fully responded to intra-arterial vasodilator infusion. Follow-up MRI revealed no
      infarct within the territory vascularized by the artery targeted by the Baby
      Trevo in 4 cases, partial infarct in 5, and complete infarct in 1. Two patients
      had parenchymal hematomas (one PH1 and one PH2). No vessel perforations,
      dissections, or subarachnoid hemorrhage were noted. CONCLUSIONS: Our initial data
      suggest that treatment of distal cerebrovascular occlusions with the Trevo XP
      3*20 mm Retriever is feasible. Although this device emerges as a promising
      technology for small and tortuous distal intracranial vessels, larger studies are
      still necessary to establish its safety and clinical benefit.

PMID- 25948593
TI  - Semimechanistic cell-cycle type-based pharmacokinetic/pharmacodynamic model of
      chemotherapy-induced neutropenic effects of diflomotecan under different dosing
      schedules.
AB  - The current work integrates cell-cycle dynamics occurring in the bone marrow
      compartment as a key element in the structure of a semimechanistic
      pharmacokinetic/pharmacodynamic model for neutropenic effects, aiming to
      describe, with the same set of system- and drug-related parameters, longitudinal
      data of neutropenia gathered after the administration of the anticancer drug
      diflomotecan (9,10-difluoro-homocamptothecin) under different dosing schedules to
      patients (n = 111) with advanced solid tumors. To achieve such an objective, the
      general framework of the neutropenia models was expanded, including one
      additional physiologic process resembling cell cycle dynamics. The main
      assumptions of the proposed model are as follows: within the stem cell
      compartment, proliferative and quiescent cells coexist, and only cells in the
      proliferative condition are sensitive to drug effects and capable of following
      the maturation chain. Cell cycle dynamics were characterized by two new
      parameters, FProl (the fraction of proliferative [Prol] cells that enters into
      the maturation chain) and kcycle (first-order rate constant governing cell cycle
      dynamics within the stem cell compartment). Both model parameters were
      identifiable as indicated by the results from a bootstrap analysis, and their
      estimates were supported by date from the literature. The estimates of FProl and
      kcycle were 0.58 and 1.94 day(-1), respectively. The new model could properly
      describe the neutropenic effects of diflomotecan after very different dosing
      scenarios, and can be used to explore the potential impact of dosing schedule
      dependencies on neutropenia prediction. 

PMID- 25948595
TI  - Dual training in general internal medicine and rheumatology: the Irish context.

PMID- 25948594
TI  - Response to: 'the effects of a brace for patellofemoral osteoarthritis targeting
      knee pain and bone marrow lesions were overestimated or not?' by Zeng et al.

PMID- 25948597
TI  - What is the impact of chronic systemic inflammation such as rheumatoid arthritis
      on mortality following cancer?
AB  - BACKGROUND: Emerging evidence links inflammation and immune competence to cancer
      progression and outcome. Few studies addressing cancer survival in the context of
      rheumatoid arthritis (RA) have reported reduced survival without accounting for
      the underlying mortality risk in RA. Whether this increased mortality is a cancer
      specific phenomenon, an effect of the decreased lifespan in RA or a combination
      of both remains unknown. METHODS: Using Swedish register data (2001-2009), we
      performed a cohort study of individuals with RA (N=34 930), matched to general
      population comparators (N=169 740), incident cancers (N=12 676) and deaths (N=14
      291). Using stratified Cox models, we estimated HRs of death associated with RA
      in the presence and absence of cancer, by stage and time since cancer diagnosis,
      for all cancers and specific sites. RESULTS: In the absence of cancer, RA was
      associated with a doubled mortality rate (HR=2.1, 95% CI 2.0 to 2.2). In the
      presence of cancer, the relative effect of RA on mortality was varied by stage.
      For cancer (tumour, node, metastases) stages I and II at diagnosis, the relative
      effect of RA on mortality was the same as in the absence of cancer. For cancers
      diagnosed at advanced stages with absolute higher mortality, the effect decreased
      (HR=1.2, 95% CI 1.1 to 1.3). These associations remained across time since cancer
      diagnosis and were reasonably similar across cancer sites. CONCLUSIONS: Much of
      the increase in mortality in patients with RA diagnosed with cancer seems to
      reside with effects of RA independently of the cancer.

PMID- 25948596
TI  - Synovial fluid hyaluronan mediates MSC attachment to cartilage, a potential novel
      mechanism contributing to cartilage repair in osteoarthritis using knee joint
      distraction.
AB  - OBJECTIVES: Knee joint distraction (KJD) is a novel, but poorly understood,
      treatment for osteoarthritis (OA) associated with remarkable 'spontaneous'
      cartilage repair in which resident synovial fluid (SF) multipotential mesenchymal
      stromal cells (MSCs) may play a role. We hypothesised that SF hyaluronic acid
      (HA) inhibited the initial interaction between MSCs and cartilage, a key first
      step to integration, and postulate that KJD environment favoured MSC/cartilage
      interactions. METHODS: Attachment of dual-labelled SF-MSCs were assessed in a
      novel in vitro human cartilage model using OA and rheumatoid arthritic (RA) SF.
      SF was digested with hyaluronidase (hyase) and its effect on adhesion was
      observed using confocal microscopy. MRI and microscopy were used to image
      autologous dual-labelled MSCs in an in vivo canine model of KJD. SF-HA was
      investigated using gel electrophoresis and densitometry. RESULTS: Osteoarthritic
      synovial fluid (OA-SF) and purified high molecular weight (MW) HA inhibited SF
      MSC adhesion to plastic, while hyase treatment of OA-SF but not RA-SF
      significantly increased MSC adhesion to cartilage (3.7-fold, p<0.05) These
      differences were linked to the SF mediated HA-coat which was larger in OA-SF than
      in RA-SF. OA-SF contained >9 MDa HA and this correlated with increases in
      adhesion (r=0.880). In the canine KJD model, MSC adhesion to cartilage was
      evident and also dependent on HA MW. CONCLUSIONS: These findings highlight an
      unappreciated role of SF-HA on MSC interactions and provide proof of concept that
      endogenous SF-MSCs are capable of adhering to cartilage in a favourable
      biochemical and biomechanical environment in OA distracted joints, offering novel
      one-stage strategies towards joint repair.

PMID- 25948598
TI  - How well are children with autism spectrum disorder doing academically at school?
      An overview of the literature.
AB  - The academic achievement of individuals with autism spectrum disorder has
      received little attention from researchers despite the importance placed on this
      by schools, families and students with autism spectrum disorder. Investigating
      factors that lead to increased academic achievement thus would appear to be very
      important. A review of the literature was conducted to identify factors related
      to the academic achievement of children and adolescents with autism spectrum
      disorder. A total of 19 studies were identified that met the inclusion criteria
      for the review. Results indicated that many individuals demonstrate specific
      areas of strength and weakness and there is a great deal of variability in
      general academic achievement across the autism spectrum. Adolescents and
      individuals with lower IQ scores were underrepresented, and few studies focused
      on environmental factors related to academic success. The importance of
      individualised assessments that profile the relative strengths and weaknesses of
      children and adolescents to aid in educational programming was highlighted.
      Further research on child-related and environmental factors that predict academic
      achievement is needed. 

PMID- 25948599
TI  - Family wellbeing of individuals with autism spectrum disorder: A scoping review.
AB  - Families play an important role in supporting individuals with autism spectrum
      disorder across the lifespan. Indicators of family wellbeing can help to
      establish benchmarks for service provision and evaluation; however, a critical
      first step is a clear understanding of the construct in question. The purpose of
      the current scoping review was to (a) summarize current conceptualizations and
      measurements of family wellbeing, (b) synthesize key findings, and (c) highlight
      gaps and limitations in the extant literature. A final review of 86 articles
      highlighted the difficulty of synthesizing findings of family wellbeing in the
      autism spectrum disorder literature due to varied measurement techniques and the
      limited use of a common theoretical direction. Considerations for future research
      are presented with an eye toward policy relevance. 

PMID- 25948600
TI  - Characterizing caregiver responses to restricted and repetitive behaviors in
      toddlers with autism spectrum disorder.
AB  - Restricted and repetitive behaviors are a core feature of autism spectrum
      disorder. This descriptive study documented the presence of restricted and
      repetitive behaviors in 85 toddlers with autism spectrum disorder as they
      interacted with their caregiver in a play interaction. For each child restricted
      and repetitive behavior, a caregiver response/non-response was coded. Caregiver
      responses were rated as successful or unsuccessful. In all, 83 toddlers
      demonstrated at least one restricted and repetitive behavior in 10 min. The most
      common child restricted and repetitive behavior was repetitive object use with 72
      children displaying at least one instance of this category of restricted and
      repetitive behavior. Overall, caregivers responded to fewer than half of their
      child's restricted and repetitive behaviors, and caregiver response varied by
      child restricted and repetitive behavior type. The most common response was
      redirection. Success varied by child restricted and repetitive behavior type and
      caregiver response--redirections were most successful for child verbal and motor
      restricted and repetitive behaviors, whereas physical or verbal responses were
      rated more successful for repetitive object use and visual restricted and
      repetitive behaviors. This study represents the first attempt to characterize how
      caregivers respond to restricted and repetitive behaviors. Toddlers with autism
      spectrum disorder are already demonstrating a variety of restricted and
      repetitive behaviors within the context of a free play sessions, and caregivers
      differentially and naturally respond to them.

PMID- 25948601
TI  - Quality versus quantity: The role of socioeconomic status on parent-reported
      service knowledge, service use, unmet service needs, and barriers to service use.
AB  - Research within the autism spectrum disorder field has emphasized the role of
      socioeconomic status in shaping parents' ability to access services for their
      child with autism spectrum disorder. However, research has yet to explore the
      possible mechanisms underlying this relationship. This study sought to address
      this research gap by examining the following questions: (1) Does parents' service
      knowledge mediate the relationship between parent socioeconomic status and
      parents' autism spectrum disorder service use? (2) What are parents' reported
      service needs and service barriers, and do these needs vary across higher and
      lower socioeconomic status groups? Quantitative results from 244 parents of a
      child with autism spectrum disorder indicate that parents' autism spectrum
      disorder service knowledge partially mediates the relationship between parent
      socioeconomic status and parents' autism spectrum disorder service use.
      Qualitative findings helped to clarify this relationship by suggesting that both
      high and low socioeconomic status parents are aware of their child's basic autism
      spectrum disorder needs. However, low socioeconomic status parents more often
      report needing more information about services and more in-home services and
      emphasize that a number of structural barriers impede their ability to meet their
      child's autism spectrum disorder needs. On the other hand, high socioeconomic
      status parents more often report a need for "higher quality services," possibly
      reflecting their better recognition of best practice guidelines. These results
      highlight the need for a multi-pronged approach to tackling unmet service needs
      within the autism spectrum disorder field. 

PMID- 25948602
TI  - The use of eye-tracking to explore social difficulties in cognitively able
      students with autism spectrum disorder: A pilot investigation.
AB  - Individuals with autism spectrum disorder do not just 'grow out of' their early
      difficulties in understanding the social world. Even for those who are
      cognitively able, autism-related difficulties continue into adulthood.
      Atypicalities attending to and interpreting communicative signals from others can
      provide barriers to success in education, employment and relationships. In the
      current study, we use eye-tracking during real social interaction to explore
      attention to social cues (e.g. face, eyes, mouth) and links to social awareness
      in a group of cognitively able University students with autism spectrum disorder
      and typically developing students from the same University. During the
      interaction, students with autism spectrum disorder showed less eye fixation and
      more mouth fixation than typically developing students. Importantly, while 63% of
      typically developing participants reported thinking they were deceived about the
      true nature of the interaction, only 9% of autism spectrum disorder participants
      picked up this subtle social signal. We argue that understanding how these social
      attentional and social awareness difficulties manifest during adulthood is
      important given the growing number of adults with autism spectrum disorder who
      are attending higher level education. These adults may be particularly
      susceptible to drop-out due to demands of coping in situations where social
      awareness is so important. 

PMID- 25948603
TI  - Changes in objectively measured BMI in children aged 4-11 years: data from the
      National Child Measurement Programme.
AB  - BACKGROUND: This study looked at the degree of weight gain between the first
      (Reception) and last year (Year 6) of primary school and how weight status in
      Reception predicts becoming overweight/obese by Year 6. METHODS: A longitudinal
      sample of 1863 children was created using two time points (2006/7, 2012/13) from
      the National Child Measurement Programme (NCMP) in South Gloucestershire. T-test
      and logistic regression were used to test the difference between the BMI z-scores
      and BMI percentiles, and predict the probability of being overweight (BMI >=
      85th) or obese (>=95th) at Year 6 based on BMI percentile in Reception. RESULTS:
      Of those children who were obese at Reception age, 68% were obese at Year 6.
      Compared with children with a BMI in the 2nd to 49th percentile range, children
      between the 75th and 84th percentiles of BMI at Reception age were 10 times more
      likely (odds ratio (OR) = 10.18, P < 0.01), and those with a BMI between the 85th
      and 94th percentiles were 13 times more likely (OR = 13.38, P < 0.01), to become
      obese by Year 6. Boys were more likely than girls to revert to a healthy weight.
      CONCLUSIONS: This is the first study to link data from the NCMP. It provides
      estimates of prevalence and offers new evidence on obesity emergence and gender
      differences.

PMID- 25948604
TI  - In Vivo IS6110 Profile Changes in a Mycobacterium tuberculosis Strain as
      Determined by Tracking over 14 Years.
AB  - Transposition and homologous recombination of IS6110 appear in Mycobacterium
      tuberculosis along in vivo sequential infections. These events were checked in
      different clones of a successful strain, M. tuberculosis Zaragoza, with the focus
      on a variant in which integration of a copy of IS6110 in the origin of
      replication (oriC) region occurred. 

PMID- 25948605
TI  - Pulmonary Fungal Infection Caused by Neoscytalidium dimidiatum.
AB  - Neoscytalidium dimidiatum is a mold known to cause onychomycosis and
      dermatomycosis; however, it is an extremely rare cause of systemic infection. We
      report a case of pulmonary infection with Neoscytalidium dimidiatum in an
      immunocompromised patient and discuss in vitro susceptibility data from this case
      and previous literature. 

PMID- 25948606
TI  - Point-Counterpoint: Cervical Cancer Screening Should Be Done by Primary Human
      Papillomavirus Testing with Genotyping and Reflex Cytology for Women over the Age
      of 25 Years.
AB  - Screening for cervical cancer with cytology testing has been very effective in
      reducing cervical cancer in the United States. For decades, the approach was an
      annual Pap test. In 2000, the Hybrid Capture 2 human papillomavirus (HPV) test
      was approved by the U.S. Food and Drug Administration (FDA) for screening women
      who have atypical squamous cells of underdetermined significance (ASCUS) detected
      by Pap test to determine the need for colposcopy. In 2003, the FDA approved
      expanding the use of the test to include screening performed in conjunction with
      a Pap test for women over the age of 30 years, referred to as "cotesting."
      Cotesting allows women to extend the testing interval to 3 years if both tests
      have negative results. In April of 2014, the FDA approved the use of an HPV test
      (the cobas HPV test) for primary cervical cancer screening for women over the age
      of 25 years, without the need for a concomitant Pap test. The approval
      recommended either colposcopy or a Pap test for patients with specific high-risk
      HPV types detected by the HPV test. This was based on the results of the ATHENA
      trial, which included more than 40,000 women. Reaction to this decision has been
      mixed. Supporters point to the fact that the primary-screening algorithm found
      more disease (cervical intraepithelial neoplasia 3 or worse [CIN3+]) and also
      found it earlier than did cytology or cotesting. Moreover, the positive
      predictive value and positive-likelihood ratio of the primary-screening algorithm
      were higher than those of cytology. Opponents of the decision prefer cotesting,
      as this approach detects more disease than the HPV test alone. In addition, the
      performance of this new algorithm has not been assessed in routine clinical use.
      Professional organizations will need to develop guidelines that incorporate this
      testing algorithm. In this Point-Counterpoint, Dr. Stoler explains why he favors
      the primary-screening algorithm, while Drs. Austin and Zhao explain why they
      prefer the cotesting approach to screening for cervical cancer. 

PMID- 25948607
TI  - Mycobacterium abscessus Complex Identification with Matrix-Assisted Laser
      Desorption Ionization-Time of Flight Mass Spectrometry.
AB  - We determined that the Vitek MS Plus matrix-assisted laser desorption ionization
      time of flight mass spectrometry using research-use-only (RUO) v.4.12 and in
      vitro-diagnostic (IVD) v.3.0 databases accurately identified 41 Mycobacterium
      abscessus subsp. abscessus and 13 M. abscessus subsp. massiliense isolates
      identified by whole-genome sequencing to the species but not the subspecies
      level, from Middlebrook 7H11 and Burkholderia cepacia selective agars. Peak
      analysis revealed three peaks potentially able to differentiate between
      subspecies. 

PMID- 25948608
TI  - Definitive Identification of Laribacter hongkongensis Acquired in the United
      States.
AB  - Laribacter hongkongensis is a potential emerging pathogen associated with
      community-acquired gastroenteritis and traveler's diarrhea. We report the
      isolation of L. hongkongensis from the stool of a patient who had no history of
      travel outside the United States. The organism was identified by phenotypic
      tests, mass spectrometry, and gene sequencing. 

PMID- 25948609
TI  - Molecular Diagnosis of Abdominal Armillifer grandis Pentastomiasis in the
      Democratic Republic of Congo.
AB  - Pentastomiasis is an emerging snake-borne parasitic zoonosis in the tropics. We
      describe a molecular and morphological study to diagnose a cluster of
      asymptomatic abdominal human infections caused by Armillifer grandis. The
      findings may indicate a silent epidemic in a rural area where severe symptomatic
      ocular cases with the same parasite species have recently surfaced. Molecular
      diagnostics are of increasing importance when patient material from remote areas
      cannot be thoroughly examined locally for logistic reasons. 

PMID- 25948610
TI  - Characterization of an Enterococcus gallinarum Isolate Carrying a Dual vanA and
      vanB Cassette.
AB  - The ability of vancomycin resistance determinants to be horizontally transferred
      within enterococci species is a concern. Identification and characterization of
      vancomycin-resistant enterococci (VRE) in a clinical isolate have a significant
      impact on infection control practices. In this study, we describe a clinical
      isolate of Enterococcus gallinarum exhibiting high-level resistance to vancomycin
      and teicoplanin. The genetic characterization of this isolate showed the presence
      of vanA and vanB genes in addition to the naturally carried vanC gene. vanA was
      identified on pA6981, a 35,608-bp circular plasmid with significant homology to
      plasmid pS177. The vanB operon was integrated into the bacterial chromosome and
      showed a high level of homology to previously reported Tn1549 and Tn5382. To the
      best of our knowledge, this is the first report of E. gallinarum carrying both
      vanA and vanB operons, indicating the importance of identifying the vancomycin
      resistance mechanism in non-E. faecium and non-E. faecalis enterococcal species. 

PMID- 25948611
TI  - Can rodents conceive hyperbolic spaces?
AB  - The grid cells discovered in the rodent medial entorhinal cortex have been
      proposed to provide a metric for Euclidean space, possibly even hardwired in the
      embryo. Yet, one class of models describing the formation of grid unit
      selectivity is entirely based on developmental self-organization, and as such it
      predicts that the metric it expresses should reflect the environment to which the
      animal has adapted. We show that, according to self-organizing models, if raised
      in a non-Euclidean hyperbolic cage rats should be able to form hyperbolic grids.
      For a given range of grid spacing relative to the radius of negative curvature of
      the hyperbolic surface, such grids are predicted to appear as multi-peaked firing
      maps, in which each peak has seven neighbours instead of the Euclidean six, a
      prediction that can be tested in experiments. We thus demonstrate that a useful
      universal neuronal metric, in the sense of a multi-scale ruler and compass that
      remain unaltered when changing environments, can be extended to other than the
      standard Euclidean plane. 

PMID- 25948612
TI  - Range bagging: a new method for ecological niche modelling from presence-only
      data.
AB  - The ecological niche is the set of environments in which a population of a
      species can persist without introduction of individuals from other locations. A
      good mathematical or computational representation of the niche is a prerequisite
      to addressing many questions in ecology, biogeography, evolutionary biology and
      conservation. A particularly challenging question for ecological niche modelling
      is the problem of presence-only modelling. That is, can an ecological niche be
      identified from records drawn only from the set of niche environments without
      records from non-niche environments for comparison? Here, I introduce a new
      method for ecological niche modelling from presence-only data called range
      bagging. Range bagging draws on the concept of a species' environmental range,
      but was inspired by the empirical performance of ensemble learning algorithms in
      other areas of ecological research. This paper extends the concept of
      environmental range to multiple dimensions and shows that range bagging is
      computationally feasible even when the number of environmental dimensions is
      large. The target of the range bagging base learner is an environmental tolerance
      of the species in a projection of its niche and is therefore an ecologically
      interpretable property of a species' biological requirements. The computational
      complexity of range bagging is linear in the number of examples, which compares
      favourably with the main alternative, Qhull. In conclusion, range bagging appears
      to be a reasonable choice for niche modelling in applications in which a presence
      only method is desired and may provide a solution to problems in other
      disciplines where one-class classification is required, such as outlier detection
      and concept learning. 

PMID- 25948613
TI  - Intrinsic tensile properties of cocoon silk fibres can be estimated by removing
      flaws through repeated tensile tests.
AB  - Silk fibres from silkworm cocoons have lower strength than spider silk and have
      received less attention as a source of high-performance fibres. In this work, we
      have used an innovative procedure to eliminate the flaws gradually of a single
      fibre specimen by retesting the unbroken portion of the fibre, after each
      fracture test. This was done multiple times so that the final test may provide
      the intrinsic fibre strength. During each retest, the fibre specimen began to
      yield once the failure load of the preceding test was exceeded. For each fibre
      specimen, a composite curve was constructed from multiple tests. The composite
      curves and analysis show that strengths of mass-produced Muga and Eri cocoon silk
      fibres increased from 446 to 618 MPa and from 337 to 452 MPa, respectively.
      Similarly, their toughness increased from 84 to 136 MJ m(-3) and from 61 to 104
      MJ m(-3), respectively. Composite plots produced significantly less inter
      specimen variations compared to values from single tests. The fibres with reduced
      flaws as a result of retests in the tested section have a tensile strength and
      toughness comparable to naturally spun dragline spider silk with a reported
      strength of 574 MPa and toughness of 91-158 MJ m(-3), which is used as a
      benchmark for developing high-performance fibres. This retesting approach is
      likely to provide useful insights into discrete flaw distributions and intrinsic
      mechanical properties of other fatigue-resistant materials.

PMID- 25948614
TI  - Testing complex networks of interaction at the onset of the Near Eastern
      Neolithic using modelling of obsidian exchange.
AB  - In this paper, we explore the conditions that led to the origins and development
      of the Near Eastern Neolithic using mathematical modelling of obsidian exchange.
      The analysis presented expands on previous research, which established that the
      down-the-line model could not explain long-distance obsidian distribution across
      the Near East during this period. Drawing from outcomes of new simulations and
      their comparison with archaeological data, we provide results that illuminate the
      presence of complex networks of interaction among the earliest farming societies.
      We explore a network prototype of obsidian exchange with distant links which
      replicates the long-distance movement of ideas, goods and people during the Early
      Neolithic. Our results support the idea that during the first (Pre-Pottery
      Neolithic A) and second (Pre-Pottery Neolithic B) phases of the Early Neolithic,
      the complexity of obsidian exchange networks gradually increased. We propose then
      a refined model (the optimized distant link model) whereby long-distance exchange
      was largely operated by certain interconnected villages, resulting in the
      appearance of a relatively homogeneous Neolithic cultural sphere. We hypothesize
      that the appearance of complex interaction and exchange networks reduced risks of
      isolation caused by restricted mobility as groups settled and argue that these
      networks partially triggered and were crucial for the success of the Neolithic
      Revolution. Communities became highly dynamic through the sharing of experiences
      and objects, while the networks that developed acted as a repository of
      innovations, limiting the risk of involution. 

PMID- 25948615
TI  - Sundew adhesive: a naturally occurring hydrogel.
AB  - Bioadhesives have drawn increasing interest in recent years, owing to their eco
      friendly, biocompatible and biodegradable nature. As a typical bioadhesive,
      sticky exudate observed on the stalked glands of sundew plants aids in the
      capture of insects and this viscoelastic adhesive has triggered extensive
      interests in revealing the implied adhesion mechanisms. Despite the significant
      progress that has been made, the structural traits of the sundew adhesive,
      especially the morphological characteristics in nanoscale, which may give rise to
      the viscous and elastic properties of this mucilage, remain unclear. Here, we
      show that the sundew adhesive is a naturally occurring hydrogel, consisting of
      nano-network architectures assembled with polysaccharides. The assembly process
      of the polysaccharides in this hydrogel is proposed to be driven by electrostatic
      interactions mediated with divalent cations. Negatively charged nanoparticles,
      with an average diameter of 231.9 +/- 14.8 nm, are also obtained from this
      hydrogel and these nanoparticles are presumed to exert vital roles in the
      assembly of the nano-networks. Further characterization via atomic force
      microscopy indicates that the stretching deformation of the sundew adhesive is
      associated with the flexibility of its fibrous architectures. It is also observed
      that the adhesion strength of the sundew adhesive is susceptible to low
      temperatures. Both elasticity and adhesion strength of the sundew adhesive reduce
      in response to lowering the ambient temperature. The feasibility of applying
      sundew adhesive for tissue engineering is subsequently explored in this study.
      Results show that the fibrous scaffolds obtained from sundew adhesive are capable
      of increasing the adhesion of multiple types of cells, including fibroblast cells
      and smooth muscle cells, a property that results from the enhanced adsorption of
      serum proteins. In addition, in light of the weak cytotoxic activity exhibited by
      these scaffolds towards a variety of mammal cells, evidence is sufficient to
      propose that sundew adhesive is a promising nanomaterial worth further
      exploitation in the field of tissue engineering.

PMID- 25948616
TI  - New record of Apoholosticha sinica (Ciliophora, Urostylida) from the UK:
      morphology, 18S rRNA gene phylogeny and notes on morphogenesis.
AB  - The benthic urostylid ciliate Apoholosticha sinicaFan et al., 2014 was isolated
      from a salt marsh at Blakeney, UK, and reinvestigated using light microscopy and
      small-subunit rRNA gene sequencing. Morphologically, it corresponds well with the
      original description. Several stages of divisional morphogenesis and
      physiological reorganization were also observed from which the following could be
      deduced: (i) the oral apparatus is completely newly built in the proter; (ii)
      frontal-ventral-transverse cirral anlage II does not produce a buccal cirrus;
      (iii) each of the posteriormost three or four anlagen contributes one transverse
      cirrus at its posterior end; (iv) a row of frontoterminal cirri originates from
      the rearmost frontal-ventral-transverse cirral anlage; (v) the last midventral
      row is formed from the penultimate frontal-ventral-transverse cirral anlage.
      Based on new data, two diagnostic features were added to the genus definition:
      (i) the midventral complex is composed of midventral pairs and midventral row and
      (ii) pretransverse ventral cirri are absent. Based on a combination of
      morphological and morphogenetic data, the genus Apoholosticha is assigned to the
      recently erected subfamily Nothoholostichinae Paiva et al., 2014, which is
      consistent with sequence comparison and phylogenetic analyses based on SSU rRNA
      gene data. It is also concluded that this benthic species, previously reported
      only from China, is not an endemic form. 

PMID- 25948617
TI  - Actinorugispora endophytica gen. nov., sp. nov., an actinomycete isolated from
      Daucus carota.
AB  - An actinomycete strain, designated YIM 690008T, was isolated from Daucus carota
      collected from South Korea and its taxonomic position was investigated by using a
      polyphasic approach. The strain grew well on most media tested and no diffusible
      pigment was produced. The aerial mycelium formed wrinkled single spores and short
      spore chains, some of which were branched. The whole-cell hydrolysates contained
      meso-diaminopimelic acid, glucose, mannose, ribose, galactose and rhamnose. The
      predominant menaquinones were MK-10(H4), MK-10(H6), MK-10(H8) and MK-10(H2). The
      polar lipids were diphosphatidylglycerol, phosphatidylcholine,
      phosphatidylinositol, phosphatidylinositol mannosides, some unknown
      phospholipids, glycolipids and polar lipids. The major fatty acids were i-C16 :
      0, ai-C17 : 0 and C18 : 1omega9c. The DNA G+C content of the genomic DNA was 63.1
      mol%. Phylogenetic analysis indicated that the isolate belongs to the family
      Nocardiopsaceae. However, based on phenotypic, chemotaxonomic and genotypic data,
      it was concluded that strain YIM 690008T represents a novel genus and novel
      species of the family Nocardiopsaceae, for which the name Actinorugispora
      endophytica gen. nov., sp. nov. (type strain YIM 690008T = DSM 46770T = JCM
      30099T = KCTC 29480T) is proposed. 

PMID- 25948618
TI  - Jiangella mangrovi sp. nov., isolated from mangrove soil.
AB  - An aerobic, Gram-stain-positive actinomycete, designated strain 3SM4-07T, was
      characterized using a polyphasic taxonomic approach. The strain produced
      branching mycelium which fragmented into short or elongated rods. The whole-cell
      hydrolysates contained ll-2,6-diaminopimelic acid as the diagnostic diamino acid,
      with glucose and ribose as the main sugars. The predominant cellular fatty acids
      were anteiso-C15  :  0, iso-C15  :  0 and iso-C16  :  0.The predominant
      menaquinone was MK-9(H4). Phospholipids consisted of diphosphatidylglycerol,
      phosphatidylglycerol, phosphatidylcholine, phosphatidylinositol and
      phosphatidylinositol mannoside. Mycolic acids were absent. The DNA G+C content
      was 72.3 mol%. Strain 3SM4-07T formed a phylogenetic line within the genus
      Jiangella and its 16S rRNA gene sequence was related most closely to Jiangella
      alkaliphila D8-87T (99.0% similarity), Jiangella muralis 15-Je-017T (98.8%),
      Jiangella alba YIM 61503T (98.6%) and Jiangella gansuensis YIM 002T (98.6%).
      However, mean DNA-DNA hybridization values revealed that strain 3SM4-07T differed
      from the closest species previously described in this genus. Data from
      phenotypic, chemotaxonomic and molecular analyses between strain 3SM4-07T and
      recognized species of the genus Jiangella indicate that strain 3SM4-07T is a
      representative of a novel species of the genus Jiangella, for which the name
      Jiangella mangrovi sp. nov. is proposed. The type strain is 3SM4-07T ( = BCC
      60398T = NBRC 109648T).

PMID- 25948619
TI  - Acetoanaerobium pronyense sp. nov., an anaerobic alkaliphilic bacterium isolated
      from a carbonate chimney of the Prony Hydrothermal Field (New Caledonia).
AB  - A novel anaerobic bacterial strain, ST07-YET, was isolated from a carbonate
      chimney of the Prony Hydrothermal Field (PHF) in New Caledonia. Cells were Gram
      stain-positive, straight rods (0.7-0.8 * 3.0-5.0 MUm) and motile by means of
      lateral flagella. Strain ST07-YET was mesophilic (optimum 35  degrees C),
      moderately alkaliphilic and halotolerant (optimum pH 8.7 and 5 g l- 1 NaCl).
      Elemental sulfur, sulfate, thiosulfate, sulfite, nitrate and nitrite were not
      used as terminal electron acceptors. Yeast extract, peptone, tryptone, Casamino
      acids, crotonate, pyruvate, galactose, maltose, sucrose, ribose, trehalose and
      glucose were used as carbon sources. Glucose fermentation led to acetate, H2 and
      CO2 formation. Arginine, serine, histidine, lysine, methionine and cysteine
      improved growth, but the Stickland reaction was negative for the combinations of
      amino acids tested. The major metabolic products from yeast extract fermentation
      were H2, CO2, acetate, butyrate, isobutyrate, isovalerate and propionate. The
      predominant cellular fatty acids were C16  :  0, C16  :  1cis9, C14  :  0 and C16
      :  1cis7 (>5 % of total fatty acids). The G+C content of the genomic DNA was
      32.9 mol%. Phylogenetic analysis revealed that strain ST07-YET was most closely
      related to Clostridium sticklandii DSM 519T and Acetoanaerobium noterae NOT-3T
      (96.7 % and 96.8 % 16S rRNA gene sequence similarity, respectively). On the basis
      of phylogenetic, chemotaxonomic and physiological properties, strain ST07-YET is
      proposed to represent a novel species of the genus Acetoanaerobium (order
      Clostridiales, phylum Firmicutes) with the name Acetoanaerobium pronyense sp.
      nov. The type strain is ST07-YET ( = DSM 27512T = JCM 19400T). 

PMID- 25948620
TI  - Identifying optimal biomarker combinations for treatment selection through
      randomized controlled trials.
AB  - BACKGROUND/AIMS: Biomarkers associated with treatment-effect heterogeneity can be
      used to make treatment recommendations that optimize individual clinical
      outcomes. To accomplish this, statistical methods are needed to generate marker
      based treatment-selection rules that can most effectively reduce the population
      burden due to disease and treatment. Compared to the standard approach of risk
      modeling to derive treatment-selection rules, a more robust approach is to
      directly minimize an unbiased estimate of total disease and treatment burden
      among a pre-specified class of rules. This problem is one of minimizing a
      weighted sum of 0-1 loss function, which is computationally challenging to solve
      due to the nonsmoothness of 0-1 loss. Huang and Fong, among others, proposed a
      method that uses the Ramp loss to approximate the 0-1 loss and solves the
      minimization problem through repetitive constrained optimizations. The algorithm
      was shown to have comparable or better performance than other comparative
      estimators in various settings. Our aim in this article is to further extend the
      algorithm to allow for variable selection in the presence of a large number of
      candidate markers. METHODS: We develop an alternative method to derive marker
      combinations to minimize the weighted sum of Ramp loss in Huang and Fong, based
      on data from randomized trials. The new algorithm estimates treatment-selection
      rules by repetitively minimizing a smooth and differentiable objective function.
      Through the use of an L1 penalty, we expand the method to allow for feature
      selection and develop an algorithm based on the coordinate descent method to
      build the treatment-selection rule. RESULTS: Through extensive simulation
      studies, we compared performance of the proposed estimator to four existing
      approaches: (1) a logistic regression risk modeling approach, and three other
      "direct optimizing" approaches including (2) the estimator in Huang and Fong, (3)
      the weighted support vector machine, and (4) the weighted logistic regression.
      The proposed estimator performs comparably to that of Huang and Fong, and
      comparably or better than other estimators. Allowing for variable selection using
      the proposed estimator in the presence of a large number of markers further
      improves treatment-selection performance. The proposed estimator is also
      advantageous for selecting variables relevant to treatment selection compared to
      L1 penalized logistic regression and weighted logistic regression. We illustrate
      the application of the proposed methods in host-genetics data from an HIV vaccine
      trial. CONCLUSION: The proposed estimator is appealing considering its
      effectiveness and conceptual simplicity. It has significant potential to
      contribute to the selection and combination of biomarkers for treatment selection
      in clinical practice.

PMID- 25948621
TI  - Surrogate markers for time-varying treatments and outcomes.
AB  - BACKGROUND: A surrogate marker is a variable commonly used in clinical trials to
      guide treatment decisions when the outcome of ultimate interest is not available.
      A good surrogate marker is one where the treatment effect on the surrogate is a
      strong predictor of the effect of treatment on the outcome. We review the
      situation when there is one treatment delivered at baseline, one surrogate
      measured at one later time point, and one ultimate outcome of interest and
      discuss new issues arising when variables are time-varying. METHODS: Most of the
      literature on surrogate markers has only considered simple settings with one
      treatment, one surrogate, and one outcome of interest at a fixed time point.
      However, more complicated time-varying settings are common in practice. In this
      article, we describe the unique challenges in two settings, time-varying
      treatments and time-varying surrogates, while relating the ideas back to the
      causal-effects and causal-association paradigms. CONCLUSION: In addition to
      discussing and extending popular notions of surrogacy to time-varying settings,
      we give examples illustrating that one can be misled by not taking into account
      time-varying information about the surrogate or treatment. We hope this article
      has provided some motivation for future work on estimation and inference in such
      settings.

PMID- 25948623
TI  - Corticospinal tract integrity measured using transcranial magnetic stimulation
      and magnetic resonance imaging in neuromyelitis optica and multiple sclerosis.
AB  - BACKGROUND: Both multiple sclerosis (MS) and neuromyelitis optica (NMO) can
      present with transverse myelitis; however, NMO symptoms are usually more severe
      and may present with more extensive axonal loss. Transcranial magnetic
      stimulation (TMS)-based input-output recruitment curves can quantitatively assess
      the excitability of corticospinal tract pathways and myelin water imaging can
      quantify the amount of myelin within this same pathway. OBJECTIVE: To compare
      differential effects of MS and NMO on TMS recruitment curves and myelin water
      imaging. METHODS: Ten healthy controls, 10 individuals with MS and 10 individuals
      with NMO completed clinical assessments, a TMS assessment and magnetic resonance
      imaging scan to measure recruitment curves and myelin water fraction in the
      corticospinal tract. RESULTS: Individuals with NMO had lower recruitment curve
      slopes (mean 13.6+/-6 MUV/%) than MS (23.6+/-11 MUV/%) and controls (21.9+/-9
      MUV/%, analysis of variance (ANOVA) P=0.05). Corticospinal tract myelin water
      fraction was lower in individuals with NMO (mean 0.17+/-0.02) compared to MS
      (0.19+/-0.02) and controls (0.20+/-0.02, ANOVA P=0.0006). CONCLUSION:
      Corticospinal pathway damage in individuals with NMO was evident by reduced
      recruitment curve slope and lower myelin water fraction. These specific measures
      of corticospinal function and structure may be used to obtain a better
      understanding and monitor brain injury caused by inflammatory central nervous
      system disorders.

PMID- 25948622
TI  - Multiple sclerosis patient-derived CSF induces transcriptional changes in
      proliferating oligodendrocyte progenitors.
AB  - BACKGROUND: Cerebrospinal fluid (CSF) is in contact with brain parenchyma and
      ventricles, and its composition might influence the cellular physiology of
      oligodendrocyte progenitor cells (OPCs) thereby contributing to multiple
      sclerosis (MS) disease pathogenesis. OBJECTIVE: To identify the transcriptional
      changes that distinguish the transcriptional response induced in proliferating
      rat OPCs upon exposure to CSF from primary progressive multiple sclerosis (PPMS)
      or relapsing remitting multiple sclerosis (RRMS) patients and other neurological
      controls. METHODS: We performed gene microarray analysis of OPCs exposed to CSF
      from neurological controls, or definitive RRMS or PPMS disease course. Results
      were confirmed by quantitative reverse transcriptase polymerase chain reaction,
      immunocytochemistry and western blot of cultured cells, and validated in human
      brain specimens. RESULTS: We identified common and unique oligodendrocyte genes
      for each treatment group. Exposure to CSF from PPMS uniquely induced branching of
      cultured progenitors and related transcriptional changes, including upregulation
      (P<0.05) of the adhesion molecule GALECTIN-3/Lgals3, which was also detected at
      the protein level in brain specimens from PPMS patients. This pattern of gene
      expression was distinct from the transcriptional programme of oligodendrocyte
      differentiation during development. CONCLUSIONS: Despite evidence of
      morphological differentiation induced by exposure to CSF of PPMS patients, the
      overall transcriptional response elicited in cultured OPCs was consistent with
      the activation of an aberrant transcriptional programme.

PMID- 25948624
TI  - Cognitive reserve in multiple sclerosis: Protective effects of education.
AB  - BACKGROUND: Recent data suggest that cognitive reserve modulates the adverse
      effects of multiple sclerosis (MS) pathology on cognitive functioning; however,
      the protective effects of education in MS are still unclear. OBJECTIVE: To
      explore education as an indicator of cognitive reserve, while controlling for
      demographic, clinical and genetic features. METHODS: A total of 419 MS patients
      and 159 healthy comparison (HC) subjects underwent a comprehensive
      neuropsychological (NP) assessment, and answered the Hospital Anxiety and
      Depression Scale. Based on the HC data, MS patients' NP scores were adjusted for
      sex, age and education; and the estimated 5(th) percentile (or 95(th) percentile,
      when appropriate) was used to identify any deficits. Patients also performed the
      Mini-Mental State Examination (MMSE); and their human leucocyte antigen HLA-DRB1
      and apolipoprotein E (ApoE) genotypes were investigated. RESULTS: Patients with
      higher education were less likely (p < 0.05) to have cognitive deficits than
      those with lower education, even when controlling for other covariates. Other
      significant predictors of cognitive deficit were: age, Expanded Disability Status
      Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), and a progressive course.
      No significant association was found with the HLA-DRB1*15:01 or ApoE epsilon4
      alleles. CONCLUSIONS: These results provide support to the use of education as a
      proxy of cognitive reserve in MS and stress the need to take into account
      education when approaching cognition in MS.

PMID- 25948625
TI  - Timing of use of cod liver oil, a vitamin D source, and multiple sclerosis risk:
      The EnvIMS study.
AB  - BACKGROUND: Low vitamin D levels have been associated with an increased risk of
      multiple sclerosis (MS), although it remains unknown whether this relationship
      varies by age. OBJECTIVE: The objective of this paper is to investigate the
      association between vitamin D3 supplementation through cod liver oil at different
      postnatal ages and MS risk. METHODS: In the Norwegian component of the
      multinational case-control study Environmental Factors In Multiple Sclerosis
      (EnvIMS), a total of 953 MS patients with maximum disease duration of 10 years
      and 1717 controls reported their cod liver oil use from childhood to adulthood.
      RESULTS: Self-reported supplement use at ages 13-18 was associated with a reduced
      risk of MS (OR 0.67, 95% CI 0.52-0.86), whereas supplementation during childhood
      was not found to alter MS risk (OR 1.01, 95% CI 0.81-1.26), each compared to non
      use during the respective period. An inverse association was found between MS
      risk and the dose of cod liver oil during adolescence, suggesting a dose-response
      relationship (p trend = 0.001) with the strongest effect for an estimated vitamin
      D3 intake of 600-800 IU/d (OR 0.46, 95% CI 0.31-0.70). CONCLUSIONS: These
      findings not only support the hypothesis relating to low vitamin D as a risk
      factor for MS, but further point to adolescence as an important susceptibility
      period for adult-onset MS.

PMID- 25948626
TI  - Menarche increases relapse risk in pediatric multiple sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) predominantly affects women with a sex ratio
      of 3:1 in contrast with a 1:1 sex ratio seen in pre-pubertal onset. Thus, puberty
      may influence MS risk differentially in males and females. How puberty may be
      associated with MS clinical features and disease course remains unknown.
      OBJECTIVE: The objective of this paper is to determine the association of
      menarche with disease course in girls with MS. METHODS: This is a longitudinal
      retrospective study from the UCSF Regional Pediatric MS Center database. We
      categorized patients by time of disease onset: pre-menarche, peri-menarche and
      post-menarche. Poisson regression models were used for within-subject relapse
      analyses offset by follow-up time. RESULTS: Seventy-six girls were included (pre
      menarche onset = 17; peri-menarche onset = 9; post-menarche onset = 50). Age of
      menarche was similar in all groups (Kruskal-Wallis p = 0.19). Relapse rate was
      the same in all three groups during the first two years of follow-up. In girls
      with follow-up overlapping at least two time periods, within-subject analyses
      showed increased relapses during the peri-menarche compared to post-menarche
      period (adjusted IRR = 8.5, 95% CI 2.5-28.7, p = 0.001). CONCLUSION: Pubertal
      status may influence MS course at least in female patients. Understanding how
      puberty influences MS clinical features may offer new insights into important
      factors regulating disease processes.

PMID- 25948627
TI  - Disability progression in relapsing MS is more than just lesions: The lesson of
      fingolimod.

PMID- 25948628
TI  - The best clinical paper on multiple sclerosis in 2014: Herodotus and Chataway -
      Commentary.

PMID- 25948629
TI  - Burden of risk variants correlates with phenotype of multiple sclerosis.
AB  - BACKGROUND: More than 100 common variants underlying multiple sclerosis (MS)
      susceptibility have been identified, but their effect on disease phenotype is
      still largely unknown. OBJECTIVE: The objective of this paper is to assess
      whether the cumulative genetic risk score of currently known susceptibility
      variants affects clinical presentation. METHODS: A cumulative genetic risk score
      was based on four human leukocyte antigen (HLA) and 106 non-HLA risk loci
      genotyped or imputed in 842 Belgian MS patients and 321 controls. Non-parametric
      analyses were applied. RESULTS: An increased genetic risk is observed for MS
      patients, including subsets such as oligoclonal band-negative and primary
      progressive MS patients, compared to controls. Within the patient group, a
      stronger association between HLA risk variants and the presence of oligoclonal
      bands, an increased immunoglobulin G (IgG) index and female gender was apparent.
      Results suggest an association between a higher accumulation of non-HLA risk
      variants and increased relapse rate as well as shorter relapse-free intervals
      after disease onset. CONCLUSION: MS patients display a significantly increased
      genetic risk compared to controls, irrespective of disease course or presence of
      oligoclonal bands. Whereas the cumulative burden of non-HLA risk variants appears
      to be reflected in the relapses of MS patients, the HLA region influences
      intrathecal IgG levels.

PMID- 25948631
TI  - Continuing professional development: learning that leads to change in individual
      and collective clinical practice.
AB  - The lack of effectiveness of traditional models of continuing professional
      development is increasingly recognised. While they can lead to increased
      knowledge of participants, research suggests that there is a general failure to
      produce meaningful and sustained changes in clinician behaviours. The aim of this
      study was to explore the effect of the Royal College of Veterinary Surgeons'
      (RCVS) new individual outcomes-focused approach to delivery of continuing
      professional development (CPD) through the reflective accounts of participant
      experiences. Content analysis of 12 summaries of their learning, produced by
      early pioneers of the Professional Key Skills (PKS) Module of the RCVS
      Certificate in Advanced Veterinary Practice, revealed that the benefits of the
      PKS-related professional development is best understood through 'a framework of
      'stakeholder' dynamics', with impact and behavioural change at the individual
      participant level having an effect on practice team behaviours, leading to
      patient, owner and business benefits. It can be concluded that, at least for
      these early pioneers, this new model for CPD has resulted in changes that have
      gone beyond knowledge accumulation to changed practitioner behaviours and
      recognisable patient, owner and business benefits. 

PMID- 25948630
TI  - Repellent effect of topical deltamethrin on blood feeding by Culicoides on
      horses.
AB  - African horse sickness (AHS) is a vectorborne disease spread by Culicoides biting
      midges. The UK's Department for Environment, Food and Rural Affairs currently
      suggests using topical deltamethrin for AHS control; however, no data are
      available regarding its efficacy in the horse. The aims of this study were to
      investigate the effect of topical deltamethrin on blood feeding by Culicoides on
      horses and to investigate which Culicoides species blood fed on horses. Three
      pairs of horses were placed in partially enclosed cages that allowed samples
      representing the Culicoides interacting with individual horses to be sampled.
      Four data collection sessions were completed before one horse from each pair was
      topically treated with 10 ml of 1 per cent deltamethrin solution and another four
      sessions were then carried out. Collected Culicoides were identified and each
      biting midge examined to see if it had blood fed. The most abundant species
      collected were C. chiopterus, C. dewulfi, C. obsoletus and C. scoticus (44.3 per
      cent) and either C. pulicaris or C. punctatus (34.7 per cent). These species were
      also more likely to have blood fed than other species, supporting their potential
      role as AHS vectors if the virus were to reach the UK. There was no significant
      effect of treatment on blood feeding by Culicoides. The results do not support
      the use of topical deltamethrin to prevent blood feeding by Culicoides on
      individual horses; however, the study does not investigate the effect that the
      widespread use of topical deltamethrin might have on vector numbers or disease
      transmission from viraemic individuals during an outbreak of AHS.

PMID- 25948632
TI  - Influence of age and body mass on the response of adolescent male pigs to
      anaesthesia.
AB  - Age and body mass affect a human's response to drugs, including anaesthetics. In
      pigs, such effects, if they occur, are likely to be pronounced: commercial breeds
      have been selected for rapid growth, meaning rapid body composition and mass
      change with age. Thirty-six male pigs were anaesthetised for CT scanning on three
      occasions (S1-3) when aged 105, 137 and 166 days and when mean (+/-sd) masses
      were 57.2+/-4.4, 88.4+/-6.2 and 114.7+/-7.6 kg, respectively. Medetomidine (5
      MUg/kg), azaperone (1 mg/kg), ketamine (5 mg/kg) and midazolam (0.25 mg/kg) were
      combined and injected intramuscularly. The times when pigs became recumbent (R1)
      and remained so (RP) were recorded. If venous cannulation was not possible five
      minutes after recumbency, 2-3 per cent isoflurane in a 1:2 O2/N2O mixture was
      delivered by mask until cannulation was possible and then discontinued. If
      anaesthetic depth was inadequate for CT scanning, a full dose (midazolam 0.25
      mg/kg, ketamine 2 mg/kg) or half dose of induction agents was administered
      intravenously. During recovery from anaesthesia, the times at first movement
      (M1), first standing attempt (S1) and successful sustained standing (SP) were
      recorded. The relationship between mass and time (minutes) from injection to each
      end point was assessed using regression analysis and linear mixed-effect models
      (LMEM); LMEM were used to assess isoflurane and intravenous anaesthetic effects.
      Analysis using LMEM showed no significant relationships between mass and the
      times from injection to the five end points. Isoflurane reduced the time to M1,
      S1 and SP (P<0.037); intravenous agents had no effect on S1 or SP (P>0.585) but
      increased the time from injection to M1 (P<0.001). In conclusion, age and mass do
      not influence the response of commercially bred pigs to the intravenous
      anaesthetic combination described. 

PMID- 25948633
TI  - EGFR Mutations and Resistance to Irreversible Pyrimidine-Based EGFR Inhibitors.
AB  - PURPOSE: Mutant selective irreversible pyrimidine-based EGFR kinase inhibitors,
      including WZ4002, CO-1686, and AZD9291, are effective in preclinical models and
      in lung cancer patients harboring the EGFR T790M gefitinib/erlotinib resistance
      mutation. However, little is known about how cancers develop acquired resistance
      to this class of EGFR inhibitors. We sought to identify and study EGFR mutations
      that confer resistance to this class of agents. EXPERIMENTAL DESIGN: We performed
      an N-ethyl-N-nitrosourea (ENU) mutagenesis screen in EGFR-mutant (sensitizing
      alone or with concurrent EGFR T790M) Ba/F3 cells and selected drug-resistant
      clones. We evaluated the sensitivity of EGFR inhibitors in models harboring drug
      resistant EGFR mutations. RESULTS: We identified 3 major drug resistance
      mutations. EGFR L718Q, L844V, and C797S cause resistance to both WZ4002 and CO
      1686 while, in contrast, only EGFR C797S leads to AZD9291 resistance. Cells
      containing an EGFR-sensitizing mutation, Del 19 or L858R, in conjunction with
      L718Q, L844V, or C797S retain sensitivity to quinazoline-based EGFR inhibitors,
      gefitinib and afatinib. The C797S mutation, in the presence of Del 19 or L858R
      and T790M, causes resistance to all current EGFR inhibitors, but
      L858R/T790M/C797S remains partially sensitive to cetuximab which leads to
      disruption of EGFR dimerization. CONCLUSIONS: Our findings provide insights into
      resistance mechanisms to irreversible pyrimidine-based EGFR inhibitors and
      identify specific genomic contexts in which sensitivity is retained to existing
      clinical EGFR inhibitors. These findings will guide the development of new
      strategies to inhibit EGFR.

PMID- 25948634
TI  - Effects of Fibrinogen Concentrate on Thrombin Generation, Thromboelastometry
      Parameters, and Laboratory Coagulation Testing in a 24-Hour Porcine Trauma Model.
AB  - INTRODUCTION: In a 24-hour porcine model of liver injury, we showed that
      fibrinogen supplementation does not downregulate endogenous fibrinogen synthesis.
      Here we report data from the same study showing the impact of fibrinogen on
      coagulation variables. MATERIALS AND METHODS: Coagulopathy was induced in 20
      German land race pigs by hemodilution and blunt liver injury. Animals randomly
      received fibrinogen concentrate (100 mg/kg) or saline. Coagulation parameters
      were assessed and thromboelastometry (ROTEM) was performed. RESULTS: Fibrinogen
      concentrate significantly reduced the prolongations of EXTEM clotting time, EXTEM
      clot formation time, and prothrombin time induced by hemodilution and liver
      injury. A decrease in clot strength was also ameliorated. Endogenous thrombin
      potential was significantly higher in the fibrinogen group than in the control
      group, 20 minutes (353 +/- 24 vs 289 +/- 22 nmol/L.min; P < .05) and 100 minutes
      (315 +/- 40 vs 263 +/- 38 nmol/L.min; P < .05) after the start of infusion.
      However, no significant between-group differences were seen in other thrombin
      generation parameters or in d-dimer or thrombin-antithrombin levels. Fibrinogen
      platelet binding was reduced following liver injury, with no significant
      differences between groups. No significant between-group differences were
      observed in any parameter at ~12 and ~24 hours. CONCLUSION: This study suggests
      that, in trauma, fibrinogen supplementation may shorten some measurements of the
      speed of coagulation initiation and produce a short-lived increase in endogenous
      thrombin potential, potentially through increased clotting substrate
      availability. Approximately 12 and 24 hours after starting fibrinogen
      concentrate/saline infusion, all parameters measured in this study were
      comparable in the 2 study groups.

PMID- 25948635
TI  - Early Identification of Asymptomatic Pulmonary Embolism Proximal to the
      Subsegmental Arteries After Gynecologic Surgery.
AB  - Few studies have assessed whether cases of asymptomatic pulmonary embolism (PE)
      in the early postoperative phase are subsegmental versus more proximal. In this
      study, we investigated whether asymptomatic PE occurring just after gynecologic
      surgery was subsegmental, and we examined the background characteristics of
      patients who experienced PE within 2 months postoperatively. All hospital records
      were reviewed, yielding a total of 2052 women who had undergone surgeries
      performed by the gynecologic oncology team between 2003 and 2013 in the National
      Kyushu Cancer Center. Asymptomatic and symptomatic postoperative PE cases
      diagnosed by multidetector computed tomography angiography or lung scan were
      identified; after excluding 2 cases of preoperative PE, there were 15 (0.73%)
      cases of postoperative PE among 2050 women. Of the 15 cases, 9 (60%) were
      diagnosed on postoperative day 1 or 2. Of the 9 women, 4 had no or minor
      symptoms/signs other than decreased oxygen saturation as measured by pulse
      oximetry (Spo 2), and PE was segmental or more proximal in 3 cases. Only 1 of the
      9 cases showed dyspnea. The remaining 4 cases showed dizziness or perspiration,
      suggesting PE. Univariate analysis showed age, operation time, hypertension, and
      preoperative d-dimer elevation to be associated with postoperative PE.
      Multivariate analysis demonstrated that a high (>= 1 ug/mL) preoperative d-dimer
      level was associated with postoperative PE (odds ratio, 6.331; 95% confidence
      interval, 1.567-25.589). Most asymptomatic PE cases occurring within 2 days
      postoperatively were segmental or more proximal. Identification of early,
      asymptomatic postoperative PE may be clinically significant because most of these
      emboli are proximal to the subsegmental arteries.

PMID- 25948636
TI  - Integrating Human Factors Engineering and Information Processing Approaches to
      Facilitate Evaluations in Criminal Justice Technology Research.
AB  - BACKGROUND: Evaluations are routinely conducted by government agencies and
      research organizations to assess the effectiveness of technology in criminal
      justice. Interdisciplinary research methods are salient to this effort.
      Technology evaluations are faced with a number of challenges including (1) the
      need to facilitate effective communication between social science researchers,
      technology specialists, and practitioners, (2) the need to better understand
      procedural and contextual aspects of a given technology, and (3) the need to
      generate findings that can be readily used for decision making and policy
      recommendations. OBJECTIVES: Process and outcome evaluations of technology can be
      enhanced by integrating concepts from human factors engineering and information
      processing. This systemic approach, which focuses on the interaction between
      humans, technology, and information, enables researchers to better assess how a
      given technology is used in practice. SUBJECTS: Examples are drawn from complex
      technologies currently deployed within the criminal justice system where
      traditional evaluations have primarily focused on outcome metrics. Although this
      evidence-based approach has significant value, it is vulnerable to fully account
      for human and structural complexities that compose technology operations.
      CONCLUSIONS: Guiding principles for technology evaluations are described for
      identifying and defining key study metrics, facilitating communication within an
      interdisciplinary research team, and for understanding the interaction between
      users, technology, and information. The approach posited here can also enable
      researchers to better assess factors that may facilitate or degrade the
      operational impact of the technology and answer fundamental questions concerning
      whether the technology works as intended, at what level, and cost.

PMID- 25948637
TI  - Internal States and Behavioral Decision-Making: Toward an Integration of Emotion
      and Cognition.
AB  - Social interactions, such as an aggressive encounter between two conspecific
      males or a mating encounter between a male and a female, typically progress from
      an initial appetitive or motivational phase, to a final consummatory phase. This
      progression involves both changes in the intensity of the animals' internal state
      of arousal or motivation and sequential changes in their behavior. How are these
      internal states, and their escalating intensity, encoded in the brain? Does this
      escalation drive the progression from the appetitive/motivational to the
      consummatory phase of a social interaction and, if so, how are appropriate
      behaviors chosen during this progression? Recent work on social behaviors in
      flies and mice suggests possible ways in which changes in internal state
      intensity during a social encounter may be encoded and coupled to appropriate
      behavioral decisions at appropriate phases of the interaction. These studies may
      have relevance to understanding how emotion states influence cognitive behavioral
      decisions at higher levels of brain function. 

PMID- 25948638
TI  - A Neural Circuit That Controls Cortical State, Plasticity, and the Gain of
      Sensory Responses in Mouse.
AB  - Neurons in the visual cortex were first found to be exquisitely selective for
      particular properties of visual stimuli in anesthetized animals, including mice.
      Studies of alert mice in an apparatus that allowed them to stand or run revealed
      that locomotion causes a change in cortical state that dramatically increases the
      magnitude of responses in neurons of the visual cortex without altering
      selectivity, effectively changing the gain of sensory responses. Locomotion also
      dramatically enhances adult plasticity in the recovery from long-term visual
      deprivation. We have studied the elements and operation of the neural circuit
      responsible for the enhancement of activity and shown that it enhances plasticity
      even in mice not free to run. The circuit consists of projections ascending from
      the midbrain locomotor region (MLR) to the basal forebrain, activating
      cholinergic and perhaps other projections to excite inhibitory interneurons
      expressing vasoactive intestinal peptide (VIP) in the visual cortex. VIP cells
      activated by locomotion inhibit interneurons that express somatostatin (SST),
      thereby disinhibiting the excitatory principal neurons and allowing them to
      respond more strongly to effective visual stimuli. These findings reveal in alert
      animals how the ascending reticular activating system described in anesthetized
      animals 50 years ago operates to control cortical state. 

PMID- 25948639
TI  - Summary: Cognition in 2014.
AB  - The goal of the 79th Cold Spring Harbor Symposia on Quantitative Biology on
      Cognition held on May 28-June 2, 2014 was to survey recent advances in cognitive
      neuroscience and assess future prospects. The symposium succeeded beyond the
      dreams of the organizers and the participants were treated to an extraordinarily
      rich feast of 58 long talks, six short talks, and 137 posters. Equally important
      to the success of the symposium was the perfect setting for informal scientific
      exchange between 260 participants generously provided by the Cold Spring Harbor
      Laboratory. The sense that emerged from the symposium was that a threshold had
      been crossed and a new era in the study of cognition was underway. My attempt
      here will be to capture that sense of awakening, to trace the strands that gave
      rise to it, and to access its implications for future discoveries. 

PMID- 25948641
TI  - Corrigendum: Animal-to-Animal Variability in Neuromodulation and Circuit
      Function.

PMID- 25948642
TI  - Spirituality and Resilience Among Mexican American IPV Survivors.
AB  - Women with abusive partners use a variety of coping strategies. This study
      examined the correlation between spirituality, resilience, and intimate partner
      violence using a cross-sectional survey of 54 Mexican American women living along
      the U.S.-Mexico border. The meaning-making coping model provides the conceptual
      framework to explore how spirituality is used as a copying strategy. Multiple
      ordinary least squares (OLS) regression results indicate women who score higher
      on spirituality also report greater resilient characteristics. Poisson regression
      analyses revealed that an increase in level of spirituality is associated with
      lower number of types of abuse experienced. Clinical, programmatic, and research
      implications are discussed.

PMID- 25948640
TI  - How Attention Affects Spatial Resolution.
AB  - We summarize and discuss a series of psychophysical studies on the effects of
      spatial covert attention on spatial resolution, our ability to discriminate fine
      patterns. Heightened resolution is beneficial in most, but not all, visual tasks.
      We show how endogenous attention (voluntary, goal driven) and exogenous attention
      (involuntary, stimulus driven) affect performance on a variety of tasks mediated
      by spatial resolution, such as visual search, crowding, acuity, and texture
      segmentation. Exogenous attention is an automatic mechanism that increases
      resolution regardless of whether it helps or hinders performance. In contrast,
      endogenous attention flexibly adjusts resolution to optimize performance
      according to task demands. We illustrate how psychophysical studies can reveal
      the underlying mechanisms of these effects and allow us to draw linking
      hypotheses with known neurophysiological effects of attention. 

PMID- 25948643
TI  - Economic Coercion and Partner Violence Against Wives in Vietnam: A Unified
      Framework?
AB  - Economic coercion refers to behaviors that control an intimate partner's ability
      to acquire, use, and maintain economic resources. Little is known about economic
      coercion in Vietnam. Using survey responses from 533 married women ages 18 to 50
      years, we estimated multinomial logistic regression models to compare the
      determinants of exposure to economic coercion only, co-occurring economic
      coercion, and any psychological, physical, or sexual intimate partner violence
      (IPV), and any IPV only, relative to no exposure. Women who, in their childhood,
      witnessed physical IPV against their mother had higher odds of exposure to co
      occurring economic coercion and any IPV as an adult (adjusted Odds Ratio = 3.54,
      95% confidence interval [CI] = [1.84, 6.83]) and any IPV only (adjust Odds Ratio
      = 1.75, 95% CI = [1.00, 3.06]), but not economic coercion only. Women who
      experienced violence as a child had higher odds of exposure to any IPV only
      (adjusted Odds Ratio = 1.63, 95% CI = [1.04, 2.56]) but not economic coercion
      only. Women with more schooling had higher odds of exposure to economic coercion
      only (adjusted Odds Ratio = 1.17, 95% CI = [1.03, 1.33]) but not other forms of
      violence. Overall, the estimates from the three models differed significantly.
      Thus, the determinants of economic coercion and common forms of IPV may differ.
      More research should focus on men's perpetration of economic coercion.

PMID- 25948644
TI  - Bystanders' Behavior in Cyberbullying Episodes: Active and Passive Patterns in
      the Context of Personal-Socio-Emotional Factors.
AB  - The present study explored bystanders' behavior in cyberbullying (CB) episodes
      among children and youth, focusing on active and passive behavior patterns. The
      study examined prevalence and characteristics of bystanders' behavior following
      CB episodes, and their active-passive intervention patterns in relation to
      personal (age, gender) and socio-emotional (self-efficacy, social support, sense
      of loneliness) factors. Of the 1,094 participants (ages 9-18), 497 (46.4%)
      reported they were bystanders to CB episodes. Of the bystanders, 55.4% were
      identified as having a passive pattern of behavior-they did not provide any help
      to cyber-victims, whereas 44.6% were identified as having an active pattern
      helping the cyber-victim. In line with the "bystanders' effect," only 35.6% of
      the bystanders offered direct help to cyber-victims after witnessing CB. When
      studying the personal-socio-emotional differences between active and passive
      bystanders, it was found that the "active bystanders" are more often girls,
      older, have more social support from significant others, and have lower levels of
      emotional loneliness than bystanders in the passive group. Differences within the
      passive and active patterns were studied as well. A logistic regression revealed
      the unique contribution of each predictor to the probability of being an active
      bystander. It was found that gender and age predicted the probability of being an
      active bystander: Girls are more likely than boys, and older bystanders are more
      likely than younger ones, to choose an active pattern and provide help to cyber
      victims. In addition, implications for CB prevention and intervention involvement
      programs to encourage bystanders to help cyber-victims are discussed.

PMID- 25948645
TI  - Recent Suicidality in the General Population: Multivariate Association With
      Childhood Maltreatment and Adult Victimization.
AB  - Three hundred and eighty-seven participants from the general population completed
      the Suicidality scale of the Detailed Assessment of Posttraumatic Stress (DAPS)
      and the Traumatic Events Survey (TES). Within the prior month, 14% of adults
      reported some degree of suicidal ideation and 2% reported an active or passive
      suicide attempt. Multinomial logistic analysis indicated that, as compared with
      nonsuicidal participants, age, childhood physical abuse, childhood sexual abuse,
      and childhood emotional abuse were associated with recent suicide attempts,
      whereas recent suicidal ideation without attempts was predicted solely by
      emotional abuse. In contrast, adult sexual or physical assaults were not
      associated with recent suicidality in any form.

PMID- 25948646
TI  - Gender-Based Violence in Rural Uttar Pradesh, India: Prevalence and Association
      With Reproductive Health Behaviors.
AB  - This study explores the prevalence of different forms of domestic violence and
      their impact on women's reproductive health behavior in rural Uttar Pradesh (UP),
      India. Data were collected as a part of a large household survey carried out in
      2009-2010. A multistage stratified systematic sampling design was used. A total
      of 4,223 married women aged 15 to 49 years and 2,274 husbands of these women were
      interviewed. Data were analyzed using bivariate and multivariate analyses. More
      than one third of married women in rural UP had experienced one or more forms of
      violence, such as verbal abuse, physical manhandling, and sexual abuse by their
      spouse. Nearly 47% of the women had experienced some form of violence during
      their last pregnancy. Significant associations were found between violence and
      incorrect reproductive health behaviors, pregnancy complications, poor birth
      preparedness, poor likelihood of institutional delivery, limited postnatal care,
      and limited spousal communication for family planning. After controlling for
      socio-economic variables in multivariate analysis, only pregnancy complications
      (odds ratio [OR] = 1.62, 95% confidence interval [CI] = [1.40, 1.85]) and lack of
      delivery preparedness (OR = 0.79, 95% CI = [0.68, 0.93]) were found to be
      significantly associated with violence. Husband's attitude and reporting of
      violence by their wives in different situations were not significantly
      associated. This study provides evidence of the association of violence on the
      reproductive health behavior of married women in rural India. The results argue
      for frontline health workers to identify and counsel pregnant women experiencing
      violence during antenatal check-up to reduce maternal morbidity and mortality.

PMID- 25948647
TI  - Why Do Women Justify Violence Against Wives More Often Than Do Men in Vietnam?
AB  - Intimate partner violence (IPV) harms the health of women and their children. In
      Vietnam, 31% of women report lifetime exposure to physical IPV, and surprisingly,
      women justify physical IPV against wives more often than do men. We compare men's
      and women's rates of finding good reason for wife hitting and assess whether
      differences in childhood experiences and resources and constraints in adulthood
      account for observed differences. Probability samples of married men ( n = 522)
      and women ( n = 533) were surveyed in Vietnam. Ordered logit models assessed the
      proportional odds for women versus men of finding more "good reasons" to hit a
      wife (never, 1-3 situations, 4-6 situations). In all situations, women found good
      reason to hit a wife more often than did men. The unadjusted odds for women
      versus men of reporting more good reasons to hit a wife were 6.55 (95% confidence
      interval [CI] = [4.82, 8.91]). This gap disappeared in adjusted models that
      included significant interactions of gender with age, number of children ever
      born, and experience of physical IPV as an adult. Having children was associated
      with justifying wife hitting among women but not men. Exposure to IPV in
      adulthood was associated with justifying wife hitting among men, but was
      negatively associated with justification of IPV among women. Further study of the
      gendered effects of resources and constraints in adulthood on attitudes about IPV
      against women will clarify women's more frequent reporting than men's that IPV
      against women is justified.

PMID- 25948648
TI  - Echoes of the Brain: Local-Scale Representation of Whole-Brain Functional
      Networks within Transmodal Cortex.
AB  - Transmodal (nonsensory-specific) regions sit at the confluence of different
      information streams, and play an important role in cognition. These regions are
      thought to receive and integrate information from multiple functional networks.
      However, little is known about (1) how transmodal cortices are functionally
      organized and (2) how this organization might facilitate information processing.
      In this article, we discuss recent findings that transmodal cortices contain a
      detailed local functional architecture of adjacent and partially overlapping
      subregions. These subregions show relative specializations, and contain traces or
      "echoes" of the activity of different large-scale intrinsic connectivity
      networks. We propose that this finer-grained organization can (1) explain how the
      same transmodal region can play a role in multiple tasks and cognitive disorders,
      (2) provide a mechanism by which different types of signals can be simultaneously
      segregated and integrated within transmodal regions, and (3) enhance current
      network- and node-level models of brain function, by showing that non-stationary
      functional connectivity patterns may be a result of dynamic shifts in subnodal
      signals. Finally, we propose that LFA may have an important role in regulating
      neural dynamics and facilitating balanced activity across the cortex to enable
      efficient and flexible high-level cognition.

PMID- 25948649
TI  - Mitochondria: Major Regulators of Neural Development.
AB  - Mitochondria are organelles derived from primitive symbiosis between archeon
      ancestors and prokaryotic alpha-proteobacteria species, which lost the capacity
      of synthetizing most proteins encoded the bacterial DNA, along the evolutionary
      process of eukaryotes. Nowadays, mitochondria are constituted by small circular
      mitochondrial DNA of 16 kb, responsible for the control of several proteins,
      including polypeptides of the electron transport chain. Throughout evolution,
      these organelles acquired the capacity of regulating energy production and
      metabolism, thus becoming central modulators of cell fate. In fact, mitochondria
      are crucial for a variety of cellular processes, including adenosine triphosphate
      production by oxidative phosphorylation, intracellular Ca(2+) homeostasis,
      generation of reactive oxygen species, and also cellular specialization in a
      variety of tissues that ultimately relies on specific mitochondrial
      specialization and maturation. In this review, we discuss recent evidence
      extending the importance of mitochondrial function and energy metabolism to the
      context of neuronal development and adult neurogenesis.

PMID- 25948651
TI  - High prevalence of menstrual migraine comorbidity in patients with premenstrual
      dysphoric disorder: Retrospective survey.

PMID- 25948652
TI  - One occipital nerve block for the short-term prevention of migraine?

PMID- 25948653
TI  - Perfusion and pH MRI in familial hemiplegic migraine with prolonged aura.
AB  - INTRODUCTION: To investigate tissue flow disturbance and hypoxia during migraine
      aura, we studied a case of familial hemiplegic migraine (FHM) using novel
      magnetic resonance imaging (MRI) techniques. CASE RESULTS: A 44-year-old male was
      admitted with suspected stroke because of confusion and aphasia. Initial
      gadolinium-based perfusion MRI showed a decrease in cerebral blood flow and an
      increase in capillary flow disturbances within the left hemisphere. Later during
      the prolonged aura phase, chemical exchange saturation transfer MRI indicated a
      drop in pH in the affected area. The patient was diagnosed with an R908Q mutation
      in the ATP1A2 gene causing FHM type 2. DISCUSSION: During prolonged aura in FHM,
      MRI shows reduced CBF, capillary flow disturbances and a possible pH drop that
      could indicate tissue hypoxia.

PMID- 25948650
TI  - From Molecular Circuit Dysfunction to Disease: Case Studies in Epilepsy,
      Traumatic Brain Injury, and Alzheimer's Disease.
AB  - Complex circuitry with feed-forward and feed-back systems regulate neuronal
      activity throughout the brain. Cell biological, electrical, and neurotransmitter
      systems enable neural networks to process and drive the entire spectrum of
      cognitive, behavioral, and motor functions. Simultaneous orchestration of
      distinct cells and interconnected neural circuits relies on hundreds, if not
      thousands, of unique molecular interactions. Even single molecule dysfunctions
      can be disrupting to neural circuit activity, leading to neurological pathology.
      Here, we sample our current understanding of how molecular aberrations lead to
      disruptions in networks using three neurological pathologies as exemplars:
      epilepsy, traumatic brain injury (TBI), and Alzheimer's disease (AD). Epilepsy
      provides a window into how total destabilization of network balance can occur.
      TBI is an abrupt physical disruption that manifests in both acute and chronic
      neurological deficits. Last, in AD progressive cell loss leads to devastating
      cognitive consequences. Interestingly, all three of these neurological diseases
      are interrelated. The goal of this review, therefore, is to identify molecular
      changes that may lead to network dysfunction, elaborate on how altered network
      activity and circuit structure can contribute to neurological disease, and
      suggest common threads that may lie at the heart of molecular circuit
      dysfunction.

PMID- 25948654
TI  - Introduction to the Sientra high-strength cohesive gel implants supplement.

PMID- 25948655
TI  - Sientra high-strength cohesive textured round implant technique: roundtable
      discussion.
AB  - : A panel of board-certified plastic surgeons chaired by Dr Grant Stevens
      convened to discuss their respective experiences with the Sientra High-Strength
      Cohesive (HSC) Textured Round silicone gel breast implants. The authors have
      implanted a combined total of approximately 2100 patients. Surgical pearls,
      complication avoidance, and practice integration tips are among the topics
      reviewed. The surgeons also present challenging cases and describe how the HSC
      textured implants helped them achieve a successful outcome. LEVEL OF EVIDENCE: 5
      Therapeutic.

PMID- 25948656
TI  - Sientra high-strength cohesive shaped technique: roundtable discussion.
AB  - A panel of board-certified plastic surgeons chaired by Dr Michael Schwartz
      convened to discuss their respective experiences with the Sientra High-Strength
      Cohesive (HSC+) shaped silicone gel breast implants (Sientra, Inc., Santa
      Barbara, CA). The authors have implanted a combined total of over 700 patients.
      Preoperative planning, surgical techniques, and practice integration tips are
      among the topics reviewed. The surgeons also present breakthrough cases and
      describe how the HSC+ textured implants helped them achieve a successful outcome.
      LEVEL OF EVIDENCE: 5Therapeutic.

PMID- 25948657
TI  - Eight-year follow-up data from the U.S. clinical trial for Sientra's FDA-approved
      round and shaped implants with high-strength cohesive silicone gel.
AB  - BACKGROUND: On March 9, 2012, the Food and Drug Administration (FDA) approved
      Sientra's premarket approval application for its portfolio of silicone gel breast
      implants based on their review of Sientra's 3-year study data from the largest
      pivotal silicone gel breast implant study to date. This included the first
      approval of shaped breast implants in the United States. OBJECTIVES: The authors
      provide an update to the 8-year safety and effectiveness of the Sientra High
      Strength silicone gel breast implants. METHODS: The Sientra Core study is an
      ongoing 10 year open-label, prospective, multi-center clinical study, which
      includes 1788 patients implanted with 3506 Sientra implants across four
      indications (Primary Augmentation, Revision Augmentation, Primary Reconstruction,
      and Revision Reconstruction). For the safety analysis, the incidence of post
      operative complications, including all breast implant-related adverse effects
      (eg, infection, asymmetry), was estimated based on Kaplan-Meier risk rates. The
      effectiveness analyses include surgeon and patient satisfaction and changes in
      bra/cup size. RESULTS: Through 8 years, the overall risk of rupture was 4.6%, the
      risk of capsular contracture was 11.8% (rates were lower when using True
      TextureTM), and the risk of reoperation was 28.3%. Out of the 580 reoperations in
      456 patients, over half of all reoperations were due to cosmetic reasons (n =
      299). The most common reasons for reoperation were capsular contracture (19.0%),
      style and/or size change (18.4%), and asymmetry (8.8%). Patient satisfaction
      remains high through 8 years, with 87% indicating that their breast implants make
      them feel more feminine than prior to enrollment. CONCLUSIONS: Safety data from
      the FDA Core study continues to support a comprehensive safety and effectiveness
      profile of Sientra's portfolio of round and shaped implants through 8 years.
      LEVEL OF EVIDENCE: 3 Therapeutic.

PMID- 25948658
TI  - Sientra primary and revision augmentation rupture trending and analysis with
      magnetic resonance imaging.
AB  - BACKGROUND: Rupture of silicone gel breast implants is a rare occurrence but
      remains one of the key surgical concerns. The objective of this article was to
      provide visibility and information on trends for the impact that patient and
      surgical characteristics play in the occurrence of rupture. OBJECTIVES: Examine
      trends in surgical techniques to better understand the etiology of implant
      rupture. METHODS: Analysis was based on Sientra's prospective, open-label, U.S.
      based clinical study of High-Strength Cohesive silicone breast implants. Patient
      and surgical characteristics were compared between ruptured and intact implants.
      RESULTS: The subset of data used for this analysis included 1792 implants in 935
      primary and revision augmentation patients implanted by 31 plastic surgeons, with
      an average follow-up of 6.6 years. The results confirm that rupture remains a
      rare adverse event. Overall, the rupture prevalence for this study was 2.4%.
      Rupture prevalence was lower among textured devices (0.8%) compared to smooth
      devices (3.8%). The prevalence of rupture was 7.8% among devices placed with a
      transaxillary incision site compared to 1.6% and 3.0% when placed with an
      inframammary or periareolar incision site, respectively. Rupture was reported in
      5.5% of the devices that received steroid pocket irrigation, compared to 1.8% of
      the devices that did not. CONCLUSIONS: Although ruptures in the Sientra study
      with the High-Strength Cohesive silicone gel implants were an uncommon
      occurrence, the authors were able to identify strong trends for the association
      of certain surgical factors and characteristics. The results show among other
      factors that an inframammary approach and a textured device were found to be
      protective against rupture. LEVEL OF EVIDENCE: 2 Therapeutic.

PMID- 25948659
TI  - Data Resource Profile: The European Union Statistics on Income and Living
      Conditions (EU-SILC).
AB  - Social and economic policies are inextricably linked with population health
      outcomes in Europe, yet few datasets are able to fully explore and compare this
      relationship across European countries. The European Union Statistics on Income
      and Living Conditions (EU-SILC) survey aims to address this gap using microdata
      on income, living conditions and health. EU-SILC contains both cross-sectional
      and longitudinal elements, with nationally representative samples of individuals
      16 years and older in 28 European Union member states as well as Iceland, Norway
      and Switzerland. Data collection began in 2003 in Belgium, Denmark, Ireland,
      Greece, Luxembourg and Austria, with subsequent expansion across Europe. By 2011,
      all 28 EU member states, plus three others, were included in the dataset.
      Although EU-SILC is administered by Eurostat, the data are output-harmonized so
      that countries are required to collect specified data items but are free to
      determine sampling strategies for data collection purposes. EU-SILC covers
      approximately 500,000 European residents for its cross-sectional survey annually.
      Whereas aggregated data from EU-SILC are publicly available
      [http://ec.europa.eu/eurostat/web/income-and-living-conditions/data/main-tables],
      microdata are only available to research organizations subject to approval by
      Eurostat. Please refer to
      [http://epp.eurostat.ec.europa.eu/portal/page/portal/microdata/eu_silc] for
      further information regarding microdata access.

PMID- 25948660
TI  - Cohort Profile: The JS High School study (JSHS): a cohort study of Korean
      adolescents.
AB  - Major aetiologies of atherosclerotic cardiovascular diseases begin in childhood
      and atherosclerotic vascular abnormalities can be observed among children and
      adolescents. Adolescent cohort studies have important advantages because they can
      observe earlier changes in vascular structure and function. The purpose of the JS
      High School study (JSHS) is to identify biomarkers predicting or indicating early
      structural and functional vascular change in adolescents. The JSHS is a
      prospective cohort study of a Korean adolescent population. The target population
      of the JSHS was first-graders (aged 14 to17 years) at a high school of South
      Korea. Enrolment and baseline examinations were conducted in years 2007, 2010,
      2011 and 2012. Among the total eligible population of 1115 students, 1071 (96.1%)
      participated in the study and completed all baseline examinations. Informed
      consent forms were obtained from each participant and his/her parent or guardian.
      Baseline examinations include: questionnaires on demographics, health behaviours,
      medical history, and depression symptoms; fasting blood analysis; anthropometric
      measurement; body impedance analysis; blood pressure measurement; radial artery
      tonometry; bone densitometry; pulmonary function tests; and carotid
      ultrasonography. Participants enrolled from 2007 through 2012 were re-examined
      after 30 months of follow-up, and those who enrolled in 2012 were re-examined
      after 24 months of follow-up. The corresponding author may be contacted for
      potential collaboration and data access.

PMID- 25948661
TI  - Health & Demographic Surveillance System Profile: Farafenni Health and
      Demographic Surveillance System in The Gambia.
AB  - The Farafenni Health and Demographic Surveillance System (Farafenni HDSS) is
      located 170 km from the coast in a rural area of The Gambia, north of the River
      Gambia. It was set up in 1981 by the UK Medical Research Council Laboratories to
      generate demographic and health information required for the evaluation of a
      village-based, primary health care programme in 40 villages. Regular updates of
      demographic events and residency status have subsequently been conducted every 4
      months. The surveillance area was extended in 2002 to include Farafenni Town and
      surrounding villages to support randomized, controlled trials. With over three
      decades of prospective surveillance, and through specific scientific
      investigations, the platform (population ~ 50,000) has generated data on:
      morbidity and mortality due to malaria in children and during pregnancy; non
      communicable disease among adults; reproductive health; and levels and trends in
      childhood and maternal mortality. Other information routinely collected includes
      causes of death through verbal autopsy, and household socioeconomic indicators.
      The current portfolio of the platform includes tracking Millennium Development
      Goal 4 (MDG4) attainments in rural Gambia and cause-of-death determination.

PMID- 25948662
TI  - Cohort Profile: The Interdisciplinary Study of Inequalities in Smoking (ISIS).
AB  - The Interdisciplinary Study of Inequalities in Smoking (ISIS) is a cohort study
      investigating the joint effects of residents' socio-demographic characteristics
      and neighbourhood attributes on the social distribution of smoking in a young
      adult population. Smoking is a behaviour with an increasingly steep social class
      gradient; smoking prevalence among young adults is no longer declining at the
      same rate as among the rest of the population, and there is evidence of growing
      place-based disparities in smoking. ISIS was established to examine these
      pressing concerns. The ISIS sample comprises non-institutionalized individuals
      aged 18-25 years, who are proficient in English and/or French and who had been
      living at their current address in Montreal, Canada, for at least 1 year at time
      of first contact. Two waves of data have been collected: baseline data were
      collected November 2011-September 2012 (n = 2093), and a second wave of data was
      collected January-June 2014 (n = 1457). Data were collected from respondents
      using a self-administered questionnaire, developed by the research team based on
      sociological theory, which includes questions concerning social, economic,
      cultural and biological capital, and activity space as well as smoking behaviour.
      Data are available upon request from [katherine.frohlich@umontreal.ca].

PMID- 25948663
TI  - Cohort Profile: The Polish-Norwegian Study (PONS) cohort.
AB  - The PONS cohort is a longitudinal observational regional study collecting
      information on health and health-related behaviours in the south-eastern part of
      Poland. The study aims at providing information on determinants of health
      differences between Poland and other countries in the region, especially related
      to premature mortality. The baseline data collection contains records for 13 172
      individuals (2010-11), between 45 and 64 years of age, from the city of Kielce
      and surrounding rural area. All cohort members were volunteer participants and
      gave informed consent prior to inclusion. Data were collected on current health
      status, medical history and health-related behaviours with focus on preventable
      causes of chronic diseases, including tobacco smoking, alcohol consumption,
      physical activity and dietary habits. In addition to an extensive questionnaire,
      blood and urine samples were collected for storage. The study is expected to
      provide valuable evidence related to various lifestyle behaviours and health, and
      insight into the usefulness of population approaches for preventive interventions
      in Polish communities. To access data or biological material or to use the sample
      to recruit participants for new studies, researchers should contact the principal
      investigator, Witold A Zatonski at: [canepid@coi.waw.pl].

PMID- 25948664
TI  - Higher usual alcohol consumption was associated with a lower 41-y mortality risk
      from coronary artery disease in men independent of genetic and common
      environmental factors: the prospective NHLBI Twin Study.
AB  - BACKGROUND: Evidence that alcohol consumption is inversely associated with long
      term coronary artery disease (CAD) mortality independent of genetic and early
      life environmental factors is lacking. OBJECTIVE: We evaluated whether alcohol
      consumption was prospectively associated with CAD mortality risk independent of
      familial factors. DESIGN: In total, 843 male twins (396 pairs and 51 unpaired
      twins) aged 42-55 y (mean: 48 y) without baseline CAD reported beer, wine, and
      spirits consumption at baseline (1969-1973) and were followed up to 2010 in the
      prospective National Heart, Lung, and Blood Institute Twin Study. Data on usual
      alcohol consumption over the past year were collected. Outcome was time to event,
      where the primary event was death from CAD and secondary events were death from
      cardiovascular disease and all causes. HRs were estimated by using frailty
      survival models, both overall and within-pair. RESULTS: There were 129 CAD deaths
      and 219 cardiovascular deaths during 41 y of follow-up. In the whole cohort,
      after adjustment for caloric intake and cardiovascular disease risk factors,
      overall HRs per 10-g increment in alcohol intake were 0.94 (95% CI: 0.89, 0.98)
      for CAD and 0.97 (95% CI: 0.93, 1.00) for cardiovascular mortality. The within
      pair adjusted HRs for a twin with 10-g higher daily alcohol consumption than his
      co-twin were 0.90 (95% CI: 0.84, 0.97) for CAD and 0.95 (95% CI: 0.90, 1.00) for
      cardiovascular disease mortality in the cohort pooled by zygosity, which remained
      similar among monozygotic twins. All 3 beverage types tended to be associated
      with lower CAD mortality risk within-pair to a similar degree. Alcohol
      consumption was not associated with total mortality risk overall or within-pair.
      CONCLUSION: Higher usual alcohol consumption is associated with lower CAD
      mortality risk, independent of germline and early life environment and adulthood
      experience shared among twins, supporting a possible causal role of alcohol
      consumption in lowering CAD death risk. This trial was registered at
      clinicaltrials.gov as NCT00005124.

PMID- 25948665
TI  - Association between intakes of magnesium, potassium, and calcium and risk of
      stroke: 2 cohorts of US women and updated meta-analyses.
AB  - BACKGROUND: Prospective data on the relation of magnesium, potassium, and calcium
      intakes with stroke risk are inconsistent, and to our knowledge, the effect of a
      combined mineral diet score has not been examined. OBJECTIVE: We examined
      associations between intakes of magnesium, potassium, and calcium and risk of
      incident stroke in 86,149 women in the Nurses' Health Study (NHS) I and 94,715
      women in the NHS II. DESIGN: In this prospective cohort study, we calculated HRs
      of stroke by quintiles of intake for each mineral and for a combined diet score
      of all 3 minerals by using multivariate Cox proportional hazard models. In
      addition, we updated meta-analyses on dietary intakes of these minerals and risk
      of stroke. RESULTS: During follow-up (30 y in the NHS I; 22 y in the NHS II) a
      total of 3780 incident stroke cases were documented. Pooled multivariate RRs of
      total stroke for women in the highest compared with the lowest quintiles were
      0.87 (95% CI: 0.78, 0.97) for total magnesium, 0.89 (95% CI: 0.80, 0.99) for
      total potassium, and 0.97 (95% CI: 0.87, 1.09) for total calcium intake. Pooled
      RRs for women in the highest compared with the lowest quintiles of a combined
      mineral diet score were 0.72 (95% CI: 0.65, 0.81) for total stroke, 0.78 (95% CI:
      0.66, 0.92) for ischemic stroke, and 0.80 (95% CI: 0.61, 1.04) for hemorrhagic
      stroke. In the updated meta-analyses of all prospective studies to date, the
      combined RR of total stroke was 0.87 (95% CI: 0.83, 0.92) for a 100-mg/d increase
      in magnesium intake, 0.91 (95% CI: 0.88, 0.94) for a 1000-mg/d increase in
      potassium intake, and 0.98 (95% CI: 0.94, 1.02) for a 300-mg/d increase in
      calcium intake. CONCLUSIONS: A combined mineral diet score was inversely
      associated with risk of stroke. High intakes of magnesium and potassium but not
      calcium were also significantly associated with reduced risk of stroke in women.

PMID- 25948666
TI  - Is the degree of food processing and convenience linked with the nutritional
      quality of foods purchased by US households?
AB  - BACKGROUND: "Processed foods" are defined as any foods other than raw
      agricultural commodities and can be categorized by the extent of changes
      occurring in foods as a result of processing. Conclusions about the association
      between the degree of food processing and nutritional quality are discrepant.
      OBJECTIVE: We aimed to determine 2000-2012 trends in the contribution of
      processed and convenience food categories to purchases by US households and to
      compare saturated fat, sugar, and sodium content of purchases across levels of
      processing and convenience. DESIGN: We analyzed purchases of consumer packaged
      goods for 157,142 households from the 2000-2012 Homescan Panel. We explicitly
      defined categories for classifying products by degree of industrial processing
      and separately by convenience of preparation. We classified >1.2 million products
      through use of barcode-specific descriptions and ingredient lists. Median
      saturated fat, sugar, and sodium content and the likelihood that purchases
      exceeded maximum daily intake recommendations for these components were compared
      across levels of processing or convenience by using quantile and logistic
      regression. RESULTS: More than three-fourths of energy in purchases by US
      households came from moderately (15.9%) and highly processed (61.0%) foods and
      beverages in 2012 (939 kcal/d per capita). Trends between 2000 and 2012 were
      stable. When classifying foods by convenience, ready-to-eat (68.1%) and ready-to
      heat (15.2%) products supplied the majority of energy in purchases. The adjusted
      proportion of household-level food purchases exceeding 10% kcal from saturated
      fat, 15% kcal from sugar, and 2400 mg sodium/2000 kcal simultaneously was
      significantly higher for highly processed (60.4%) and ready-to-eat (27.1%) food
      purchases than for purchases of less-processed foods (5.6%) or foods requiring
      cooking/preparation (4.9%). CONCLUSIONS: Highly processed food purchases are a
      dominant, unshifting part of US purchasing patterns, but highly processed foods
      may have higher saturated fat, sugar, and sodium content than less-processed
      foods. Wide variation in nutrient content suggests food choices within categories
      may be important.

PMID- 25948667
TI  - Gestational changes in iodine status in a cohort study of pregnant women from the
      United Kingdom: season as an effect modifier.
AB  - BACKGROUND: Iodine is required throughout pregnancy for thyroid hormone
      production, which is essential for fetal brain development. Studies of iodine
      status in pregnant women from the United Kingdom (UK) have focused on early
      gestation (<16 wk). Data on the effect of advancing gestation on urinary iodine
      excretion are conflicting, with suggestions of both an increase and a decrease.
      OBJECTIVES: The aims were to evaluate iodine status in a cohort of UK pregnant
      women and to explore how it changes throughout gestation. DESIGN: We used samples
      and data from 230 UK pregnant women who were recruited to the Selenium in
      PRegnancy INTervention study. Iodine concentration was measured in spot-urine
      samples that were collected at ~12, 20, and 35 wk of gestation; creatinine
      concentration was also measured to correct for urine dilution. A linear mixed
      model was used to explore the effect of gestational week on iodine-to-creatinine
      ratio, with change in season, body mass index, daily milk intake, and maternal
      age controlled for. RESULTS: The median urinary iodine concentration from urine
      samples collected at all time points (n = 662) was 56.8 MUg/L, and the iodine-to
      creatinine ratio was 116 MUg/g, thus classifying this cohort as mildly-to
      moderately iodine deficient. The median iodine-to-creatinine ratios at 12, 20,
      and 35 wk were 102.5, 120.0, and 126.0 MUg/g, respectively. Only 3% of women were
      taking iodine-containing prenatal supplements. The iodine-to-creatinine ratio
      increased with advancing gestation, and there was a significant interaction
      between gestational week and season (P = 0.026). For a 1-wk increase in
      gestation, the iodine-to-creatinine ratio increased by a factor of 1.05 (95% CI:
      1.02, 1.08) in winter and by a factor of 1.04 (95% CI: 1.00, 1.08) in summer.
      CONCLUSIONS: This group of UK pregnant women was mildly-to-moderately iodine
      deficient at all trimesters, which is of public health concern. The finding that
      the iodine-to-creatinine ratio increased over the course of gestation may not be
      generalizable to populations with different iodine status from ours and merits
      further investigation. This trial was registered at www.isrctn.com as
      ISRCTN37927591.

PMID- 25948668
TI  - Genetic modifiers of folate, vitamin B-12, and homocysteine status in a cross
      sectional study of the Canadian population.
AB  - BACKGROUND: Genetic variation can cause variable responses to environmental
      stimuli. A number of single-nucleotide polymorphisms (SNPs) have been associated
      with B vitamin status or chronic diseases related to vitamin B-12 and folate
      metabolism. OBJECTIVE: Our objective was to identify associations between common
      SNPs in genes related to folate and vitamin B-12 metabolism or associated with B
      vitamin-related chronic diseases and biomarkers of nutrient status in a
      population exposed to folic acid fortification. DESIGN: A panel of 116 SNPs was
      sequenced by using the Sequenom iPLEX Gold platform in a sample of 3114 adults
      aged 20-79 y from the Canadian Health Measures Survey, cycle 1. Associations
      between these SNPs and red blood cell (RBC) folate, serum vitamin B-12, and
      plasma total homocysteine were determined. RESULTS: Twenty-one SNPs and 6
      haplotype blocks were associated with RBC folate, serum vitamin B-12, and/or
      plasma homocysteine concentrations. Vitamin status was associated mainly with
      SNPs in genes directly involved in vitamin absorption/uptake (CUBN, CD320),
      transport (TCN1, TCN2), or metabolism (BHMT2, CBS, MTHFR, MUT, SHMT1). Other SNPs
      included those in the DNMT2, DPEP1, FUT2, NOX4, and PON1 genes. CONCLUSIONS: We
      identified novel associations between SNPs in CD320 and DNMT2, which had been
      previously associated with neural tube defects, and vitamin B-12 status, as well
      as between SNPs in SHMT1, which had been previously associated with colorectal
      cancer and cardiovascular disease risk, and RBC folate status. These novel
      associations provide a plausible metabolic rationale for the association of these
      SNPs with B vitamin-related diseases. We also observed a novel association
      between an SNP in CUBN with RBC folate and confirmed the association of a number
      of SNPs with B vitamin status in this large cross-sectional study.

PMID- 25948669
TI  - Genetically high plasma vitamin C, intake of fruit and vegetables, and risk of
      ischemic heart disease and all-cause mortality: a Mendelian randomization study.
AB  - BACKGROUND: High intake of fruit and vegetables as well as high plasma vitamin C
      concentrations have been associated with low risk of ischemic heart disease in
      prospective studies, but results from randomized clinical trials have been
      inconsistent. OBJECTIVE: We tested the hypothesis that genetically high
      concentrations of plasma vitamin C, such as with high intake of fruit and
      vegetables, are associated with low risk of ischemic heart disease and all-cause
      mortality. DESIGN: We used a Mendelian randomization approach and genotyped for
      solute carrier family 23 member 1 (SLC23A1) rs33972313 in the sodium-dependent
      vitamin C transporter 1 in 97,203 white individuals of whom 10,123 subjects had
      ischemic heart disease, and 8477 subjects died. We measured plasma vitamin C in
      3512 individuals and included dietary information on 83,256 individuals. RESULTS:
      The SLC23A1 rs33972313 G allele was associated with 11% higher plasma vitamin C.
      The multivariable adjusted HRs for highest compared with lowest fruit and
      vegetable intakes were 0.87 (95% CI: 0.78, 0.97; P = 0.01) for ischemic heart
      disease and 0.80 (95% CI: 0.73, 0.88; P < 0.001) for all-cause mortality.
      Corresponding HRs for rs33972313 GG (93%) compared with AA plus AG (7%) genotypes
      were 0.95 (95% CI: 0.88, 1.02; P = 0.21) and 0.96 (0.88, 1.03; P = 0.29),
      respectively. In an instrumental variable analysis, the OR for genetically
      determined 25% higher plasma vitamin C concentrations was 0.90 (95% CI: 0.75,
      1.08; P = 0.27) for ischemic heart disease and 0.88 (0.72, 1.08; P = 0.22) for
      all-cause mortality. CONCLUSIONS: High intake of fruit and vegetables was
      associated with low risk of ischemic heart disease and all-cause mortality.
      Although the 95% CI for genetically high plasma vitamin C concentrations
      overlapped 1.0, which made certain statistical inferences difficult, effect sizes
      were comparable to those for fruit and vegetable intake. Thus, judging by the
      effect size, our data cannot exclude that a favorable effect of high intake of
      fruit and vegetables could in part be driven by high vitamin C concentrations.

PMID- 25948671
TI  - Dietary saturated fat intake and atherosclerotic vascular disease mortality in
      elderly women: a prospective cohort study.
AB  - BACKGROUND: The reduction of saturated fatty acid (SFA) intake has been the basis
      of long-standing dietary recommendations. However, recent epidemiologic studies
      have reported conflicting evidence in the relation between SFA consumption and
      risk of atherosclerotic vascular disease (ASVD) mortality. OBJECTIVE: We
      investigated the association of SFA intake with serum lipid profiles and ASVD
      mortality in a population-based 10-y cohort study. DESIGN: At baseline (1998)
      1469 women living in Perth, Western Australia, with a mean +/- SD age of 75.2 +/-
      2.7 y had SFA intake measured by using a validated food-frequency questionnaire.
      Outcome data were serum lipids at baseline and ASVD deaths over 10 y (13,649
      person-years of follow-up), retrieved from the Western Australian Data Linkage
      System. Other risk factors for ASVD were assessed and adjusted for in
      multivariable analyses. RESULTS: ASVD deaths occurred in 9.1% (134) of
      participants. The highest quartile of SFA intake (>31.28 g/d) had an ~16%
      cumulative mortality risk compared with ~5% in the lowest quartile (<17.39 g/d)
      (HR: 3.07; 95% CI: 1.54, 6.11; P = 0.001). Baseline SFA intake was associated
      with baseline serum total and LDL cholesterol in multivariable-adjusted models
      (beta: 0.199, SE: 0.056, P < 0.001 and beta: 0.190, SE: 0.051, P < 0.001,
      respectively). However, baseline serum total and LDL cholesterol were not
      associated with ASVD mortality. CONCLUSIONS: High SFA intake was associated with
      the risk of ASVD mortality in this population of elderly women. Although there
      was a strong positive association between SFA intake and LDL cholesterol, LDL
      cholesterol was not associated with ASVD mortality in this cohort. Nevertheless,
      these data support dietary advice to reduce SFA intake.

PMID- 25948670
TI  - Longitudinal associations of nutritional factors with glycated hemoglobin in
      youth with type 1 diabetes: the SEARCH Nutrition Ancillary Study.
AB  - BACKGROUND: Improved glycated hemoglobin (Hb A1c) delays the progression of
      microvascular and macrovascular complications in individuals with type 1 diabetes
      (T1D). We previously showed that higher baseline intakes of n-3 (omega-3) fatty
      acids and leucine are associated with preserved beta cell function 2 y later in
      youth with T1D. OBJECTIVE: In the current study, we extend this work to explore
      the longitudinal associations of nutritional factors with Hb A1c in youth with
      T1D. DESIGN: We included 908 T1D youth with baseline and follow-up Hb A1c
      measurements. Nutritional factors assessed at baseline were as follows:
      breastfeeding status and timing of complimentary food introduction; intakes of
      leucine, carbohydrates, protein, fat, and fiber estimated from a food-frequency
      questionnaire (FFQ); and plasma biomarkers for vitamins D and E, eicosapentaenoic
      acid (EPA), and docosahexaenoic acid. We fit linear regression models adjusted
      for baseline Hb A1c, sociodemographic variables, diabetes-related variables, time
      between baseline and follow-up visits, saturated fat, physical activity, and for
      FFQ-derived nutrients, total calories. The vitamin D model was further adjusted
      for season and body mass index z score. RESULTS: The mean +/- SD age and diabetes
      duration at baseline was 10.8 +/- 3.9 y and 10.1 +/- 5.8 mo, respectively. A
      total of 9.3% of participants had poor Hb A1c (value >=9.5%) at baseline, which
      increased to 18.3% during follow-up (P < 0.0001). Intakes of EPA (beta = -0.045,
      P = 0.046), leucine (beta = -0.031, P = 0.0004), and protein (beta = -0.003, P =
      0.0002) were significantly negatively associated with follow-up Hb A1c after
      adjustment for confounders. Intake of carbohydrates was significantly positively
      (beta = 0.001, P = 0.003) associated with follow-up Hb A1c after adjustment for
      confounders. CONCLUSIONS: Several nutritional factors may be associated with Hb
      A1c during early stages of disease progression in youth recently diagnosed with
      T1D. In addition to the overall role of major macronutrients such as
      carbohydrates and protein, leucine and n-3 fatty acid intakes, such as of EPA,
      may be important for long-term glycemic control.

PMID- 25948672
TI  - Amino acids, lipid metabolites, and ferritin as potential mediators linking red
      meat consumption to type 2 diabetes.
AB  - BACKGROUND: Habitual red meat consumption was consistently related to a higher
      risk of type 2 diabetes in observational studies. Potentially underlying
      mechanisms are unclear. OBJECTIVE: This study aimed to identify blood metabolites
      that possibly relate red meat consumption to the occurrence of type 2 diabetes.
      DESIGN: Analyses were conducted in the prospective European Prospective
      Investigation into Cancer and Nutrition-Potsdam cohort (n = 27,548), applying a
      nested case-cohort design (n = 2681, including 688 incident diabetes cases).
      Habitual diet was assessed with validated semiquantitative food-frequency
      questionnaires. Total red meat consumption was defined as energy-standardized
      summed intake of unprocessed and processed red meats. Concentrations of 14 amino
      acids, 17 acylcarnitines, 81 glycerophospholipids, 14 sphingomyelins, and
      ferritin were determined in serum samples from baseline. These biomarkers were
      considered potential mediators of the relation between total red meat consumption
      and diabetes risk in Cox models. The proportion of diabetes risk explainable by
      biomarker adjustment was estimated in a bootstrapping procedure with 1000
      replicates. RESULTS: After adjustment for age, sex, lifestyle, diet, and body
      mass index, total red meat consumption was directly related to diabetes risk [HR
      for 2 SD (11 g/MJ): 1.26; 95% CI: 1.01, 1.57]. Six biomarkers (ferritin, glycine,
      diacyl phosphatidylcholines 36:4 and 38:4, lysophosphatidylcholine 17:0, and
      hydroxy-sphingomyelin 14:1) were associated with red meat consumption and
      diabetes risk. The red meat-associated diabetes risk was significantly (P <
      0.001) attenuated after simultaneous adjustment for these biomarkers [biomarker
      adjusted HR for 2 SD (11 g/MJ): 1.09; 95% CI: 0.86, 1.38]. The proportion of
      diabetes risk explainable by respective biomarkers was 69% (IQR: 49%, 106%).
      CONCLUSION: In our study, high ferritin, low glycine, and altered hepatic-derived
      lipid concentrations in the circulation were associated with total red meat
      consumption and, independent of red meat, with diabetes risk. The red meat
      associated diabetes risk was largely attenuated after adjustment for selected
      biomarkers, which is consistent with the presumed mediation hypothesis.

PMID- 25948673
TI  - Association of serum retinoic acid with hepatic steatosis and liver injury in
      nonalcoholic fatty liver disease.
AB  - BACKGROUND: Retinoic acid (RA), an active metabolite of vitamin A (retinol), has
      been implicated in the regulation of lipid metabolism and hepatic steatosis in
      animal models. However, the relation between RA and liver histology in patients
      with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis
      (NASH) is unknown. OBJECTIVE: This study aimed at examining the association of RA
      with NAFLD and NASH in Chinese subjects. DESIGN: Serum RA concentration was
      determined by ELISA in 41 control subjects, 45 patients with NAFLD, and 38
      patients with NASH. The associations of RA with adiposity, serum glucose, lipid
      profiles, and markers of liver damage were studied. Moreover, both mRNA and
      protein levels of retinoic X receptor alpha (RXRalpha) in the liver were analyzed
      in subjects with different degrees of hepatic steatosis. RESULTS: Serum RA
      concentrations in patients with NAFLD (1.42 +/- 0.47 ng/mL) and NASH (1.14 +/-
      0.26 ng/mL) were significantly lower than those in control subjects (2.70 +/-
      0.52 ng/mL) (P < 0.01). Furthermore, serum RA concentrations were significantly
      different between subjects with normal glucose tolerance and those with type 2
      diabetes in control [2.87 +/- 0.52 (n = 28) vs. 2.32 +/- 0.44 ng/mL (n = 13)],
      NAFLD [1.61 +/- 0.37 (n = 29) vs. 1.28 +/- 0.41 ng/mL (n = 16)], and NASH [1.35
      +/- 0.34 (n = 24) vs. 1.07 +/- 0.29 ng/mL (n = 14)] groups. In human liver
      tissue, RXRalpha mRNA expression was inversely correlated with the exacerbation
      of hepatic steatosis. Both serum RA concentrations and RXRalpha mRNA levels were
      inversely correlated with intrahepatic triglyceride content (r = -0.700, P <
      0.001, and r = -0.611, P = 0.002, respectively). Compared with grade 0 severity,
      the concentration of RXRalpha protein was lower in more severe grades in patients
      with NAFLD. CONCLUSION: These results show that circulating RA concentrations
      were lower in subjects with NAFLD and were associated with hepatic lipid
      metabolism and insulin resistance. This trial was registered at
      clinicaltrials.gov as NCT01940263.

PMID- 25948674
TI  - Effects of a Topical Saffron (Crocus sativus L) Gel on Erectile Dysfunction in
      Diabetics: A Randomized, Parallel-Group, Double-Blind, Placebo-Controlled Trial.
AB  - Erectile dysfunction is a man's persistent or recurrent inability to achieve and
      maintain erection for a satisfactory sexual relationship. As diabetes is a major
      risk factor for erectile dysfunction, the prevalence of erectile dysfunction
      among diabetic men has been reported as 35% to 90%. This randomized, parallel
      group, double-blind, placebo-controlled trial investigated the effects of a
      topical saffron (Crocus sativus L) gel on erectile dysfunction in diabetic men.
      Patients were randomly allocated to 2 equal groups (with 25 patients each). The
      intervention group was treated with topical saffron, and the control received a
      similar treatment with placebo. The 2 groups were assessed using the
      International Index of Erectile Function Questionnaire before the intervention
      and 1 month after the intervention. Compared to placebo, the prepared saffron gel
      could significantly improve erectile dysfunction in diabetic patients (P < .001).
      This preliminary evidence suggests that saffron can be considered as a treatment
      option for diabetic men with erectile dysfunction. 

PMID- 25948675
TI  - BRCAPRO 6.0 Model Validation in Male Patients Presenting for BRCA Testing.
AB  - BACKGROUND: BRCAPRO is a risk assessment model to estimate the risk of carrying a
      BRCA mutation. BRCA mutation carriers are at higher risk of developing breast,
      ovarian, pancreatic, and prostate cancer. BRCAPRO was developed for women and
      found to be superior to other risk assessment models. The present study evaluated
      the validity of BRCAPRO at predicting the risk of male patients carrying a BRCA
      mutation. PATIENTS AND METHODS: A total of 146 men who presented for genetic
      counseling and testing from February1997 to September 2011, and their test
      results were included in the present study. BRCAPRO risk assessment for all
      patients was calculated using the BRCAPRO clinical CancerGene assessment
      software. RESULTS: The mean age at presentation was 57 years. Of the 146
      patients, 48 had breast cancer, 18 had pancreatic cancer, 39 had prostate cancer,
      27 had other primary cancers, and 37 had no cancer. Fifty patients (34%) tested
      positive for a BRCA mutation (22 BRCA1, 27 BRCA2, and 1 BRCA1 and BRCA2). The
      mean BRCAPRO score for all patients was 24.96%. The BRCAPRO score was
      significantly higher for patients who tested positive for a BRCA mutation (46.19%
      vs. 13.9%, p < .01). The area under the receiver operating characteristics curve
      was 0.83 for all patients for the BRCAPRO score to predict the risk of carrying a
      BRCA mutation. At a cutoff point of 30.02%, the sensitivity, specificity,
      positive predictive value, and negative predictive value were 0.74, 0.81, 0.67,
      and 0.86, respectively. CONCLUSION: BRCAPRO appears to be a valid risk assessment
      tool for determining the risk of carrying a BRCA mutation in men. IMPLICATIONS
      FOR PRACTICE: Men carrying genetic mutations in the BRCA gene have a greater risk
      than the general population of developing certain types of cancer, including
      breast, pancreatic, and prostate cancer. BRCAPRO is a risk assessment model that
      predicts the risk of carrying a BRCA mutation. The present study aimed at
      validating BRCAPRO for use with men seen for genetic counseling, whether affected
      by cancer or not. The data available for 146 patients revealed that BRCAPRO was
      effective at identifying patients at risk of BRCA mutation. These findings could
      help in identifying a subset of high-risk patients who should proceed to genetic
      testing.

PMID- 25948677
TI  - Chemotherapy-Induced Nausea and Vomiting: Time for More Emphasis on Nausea?

PMID- 25948678
TI  - Observations on Three Endpoint Properties and Their Relationship to Regulatory
      Outcomes of European Oncology Marketing Applications.
AB  - BACKGROUND: Guidance and exploratory evidence indicate that the type of endpoints
      and the magnitude of their outcome can define a therapy's clinical activity;
      however, little empirical evidence relates specific endpoint properties with
      regulatory outcomes. MATERIALS AND METHODS: We explored the relationship of 3
      endpoint properties to regulatory outcomes by assessing 50 oncology marketing
      authorization applications (MAAs; reviewed from 2009 to 2013). RESULTS: Overall,
      16 (32%) had a negative outcome. The most commonly used hard endpoints were
      overall survival (OS) and the duration of response or stable disease. OS was a
      component of 91% approved and 63% failed MAAs. The most commonly used surrogate
      endpoints were progression-free survival (PFS), response rate, and health-related
      quality of life assessments. There was no difference (p = .3801) between the
      approved and failed MAA cohorts in the proportion of hard endpoints used. A mean
      of slightly more than four surrogate endpoints were used per approved MAA
      compared with slightly more than two for failed MAAs. Longer OS and PFS duration
      outcomes were generally associated with approvals, often when not statistically
      significant. The approved cohort was associated with a preponderance of
      statistically significant (p < .05) improvements in primary endpoints (p < .0001
      difference between the approved and failed groups). CONCLUSION: Three key
      endpoint properties (type of endpoint [hard/surrogate], magnitude of an endpoint
      outcome, and its statistical significance) are consistent with the European
      Medicines Agency guidance and, notwithstanding the contribution of unique disease
      specific circumstances, are associated with a predictable positive outcome for
      oncology MAAs. IMPLICATIONS FOR PRACTICE: Regulatory decisions made by the
      European Medicines Agency determine which new medicines will be available to
      European prescribers and for which therapeutic indications. Regulatory success or
      failure can be influenced by many factors. This study assessed three key
      properties of endpoints used in preauthorization trials (type of endpoint
      [hard/surrogate], magnitude of endpoint outcome, and its statistical
      significance) and whether they are associated with a positive regulatory outcome.
      Clinicians can use these properties, which are described in the publicly
      available European public assessment reports, to help guide their understanding
      of the clinical effect of new oncologic therapies.

PMID- 25948676
TI  - Clinicopathological and Immunohistochemical Characteristics in Male Breast
      Cancer: A Retrospective Case Series.
AB  - BACKGROUND: Due to its rarity, male breast cancer (mBC) remains an inadequately
      characterized disease, and current evidence for treatment derives from female
      breast cancer (FBC). METHODS: We retrospectively analyzed the clinicopathological
      characteristics, treatment patterns, and outcomes of mBCs treated from 2000 to
      2013. RESULTS: From a total of 97 patients with mBC, 6 (6.2%) with ductal in situ
      carcinoma were excluded, and 91 patients with invasive carcinoma were analyzed.
      Median age was 65 years (range: 25-87 years). Estrogen receptors were positive in
      88 patients (96.7%), and progesterone receptors were positive in 84 patients
      (92.3%). HER-2 was overexpressed in 13 of 85 patients (16%). Median follow-up was
      51.5 months (range: 0.5-219.3 months). Five-year progression-free survival (PFS)
      was 50%, whereas overall survival (OS) was 68.1%. Patients with grades 1 and 2
      presented 5-year PFS of 71% versus 22.5% for patients with grade 3 disease; 5
      year OS was 85.7% for patients with grades 1 and 2 versus 53.3% of patients with
      grade 3. Ki-67 score >20% and adjuvant chemotherapy were also statistically
      significant for OS on univariate analyses. Twenty-six of 87 patients (29.8%)
      experienced recurrent disease and 16 of 91 patients (17.6%) developed a second
      neoplasia. CONCLUSION: Male breast cancer shows different biological patterns
      compared with FBC, with higher positive hormone-receptor status and lower HER-2
      overexpression. Grade 3 and Ki-67 >20% were associated with shorter OS.
      IMPLICATIONS FOR PRACTICE: There is little evidence that prognostic features
      established in female breast cancer, such as grading and Ki-67 labeling index,
      could be applied to male breast cancer as well. This study found that grade 3 was
      associated with shorter overall survival and a trend for Ki-67 >20%; this could
      help in choosing the best treatment option in the adjuvant setting. Many
      questions remain regarding the impact of HER-2 positivity on survival and
      treatment with adjuvant anti-HER-2 therapy. Regarding metastatic male breast
      cancer, the results suggest that common regimens of chemo-, endocrine and
      immunotherapy used in female breast cancer are safe and effective for men. Male
      breast cancer patients show a higher incidence of second primary tumors,
      especially prostate and colon cancers and should therefore be carefully
      monitored.

PMID- 25948679
TI  - Plasma Adrenomedullin and Allelic Variation in the ADM Gene and Kidney Disease in
      People With Type 2 Diabetes.
AB  - Production of adrenomedullin (ADM), a vasodilator peptide, increases in response
      to ischemia and hypoxia in the vascular wall and the kidney. This may be an
      adaptive response providing protection against organ damage. We investigated the
      hypothesis that ADM has a nephroprotective effect in two prospective cohorts of
      patients with type 2 diabetes recruited in France. The highest tertile of plasma
      MR-proADM (a surrogate for ADM) concentration at baseline was associated with the
      risk of renal outcomes (doubling of plasma creatinine concentration and/or
      progression to end-stage renal disease) during follow-up in both cohorts. Four
      SNPs in the ADM gene region were associated with plasma MR-proADM concentration
      at baseline and with eGFR during follow-up in both cohorts. The alleles
      associated with lower eGFR were also associated with lower plasma MR-proADM
      level. In conclusion, plasma MR-proADM concentration was associated with renal
      outcome in patients with type 2 diabetes. Our data suggest that the ADM gene
      modulates the genetic susceptibility to nephropathy progression. Results are
      consistent with the hypothesis of a reactive rise of ADM in diabetic nephropathy,
      blunted in risk alleles carriers, and with a nephroprotective effect of ADM. A
      possible therapeutic effect of ADM receptor agonists in diabetic renal disease
      would be worth investigating. 

PMID- 25948681
TI  - Using Genetic Variants to Assess the Relationship Between Circulating Lipids and
      Type 2 Diabetes.
AB  - The effects of dyslipidemia on the risk of type 2 diabetes (T2D) and related
      traits are not clear. We used regression models and 140 lipid-associated genetic
      variants to estimate associations between circulating HDL cholesterol (HDL-C),
      LDL cholesterol (LDL-C), and triglycerides and T2D and related traits. Each
      genetic test was corrected for effects of variants on the other two lipid types
      and surrogates of adiposity. We used the largest data sets available: 34,840 T2D
      case and 114,981 control subjects from the DIAGRAM (DIAbetes Genetics Replication
      And Meta-analysis) consortium and up to 133,010 individuals without diabetes for
      insulin secretion and sensitivity from the MAGIC (Meta-Analyses of Glucose and
      Insulin-related traits Consortium) and GENESIS (GENEticS of Insulin Sensitivity)
      studies. Eight of 21 associations between groups of variants and diabetes traits
      were significant at the nominal level, including those between genetically
      determined lower HDL-C (beta = -0.12, P = 0.03) and T2D and genetically
      determined lower LDL-C (beta = -0.21, P = 5 * 10(-6)) and T2D. Although some of
      these may represent causal associations, we discuss why caution must be used when
      using Mendelian randomization in the context of circulating lipid levels and
      diabetes traits. In conclusion, we found evidence of links between genetic
      variants associated with lipids and T2D, but deeper knowledge of the underlying
      genetic mechanisms of specific lipid variants is needed before drawing definite
      conclusions about causality based on Mendelian randomization methodology. 

PMID- 25948680
TI  - Maternal High-Fat Feeding Increases Placental Lipoprotein Lipase Activity by
      Reducing SIRT1 Expression in Mice.
AB  - This study investigated how maternal overnutrition and obesity regulate
      expression and activation of proteins that facilitate lipid transport in the
      placenta. To create a maternal overnutrition and obesity model, primiparous
      C57BL/6 mice were fed a high-fat (HF) diet throughout gestation. Fetuses from HF
      fed dams had significantly increased serum levels of free fatty acid and body
      fat. Despite no significant difference in placental weight, lipoprotein lipase
      (LPL) protein levels and activity were remarkably elevated in placentas from HF
      fed dams. Increased triglyceride content and mRNA levels of CD36, VLDLr, FABP3,
      FABPpm, and GPAT2 and -3 were also found in placentas from HF-fed dams. Although
      both peroxisome proliferator-activated receptor-gamma (PPARgamma) and
      CCAAT/enhancer binding protein-alpha protein levels were significantly increased
      in placentas of the HF group, only PPARgamma exhibited a stimulative effect on
      LPL expression in cultured JEG-3 human trophoblasts. Maternal HF feeding
      remarkably decreased SIRT1 expression in placentas. Through use of an SIRT1
      activator and inhibitor and cultured trophoblasts, an inhibitory effect of SIRT1
      on LPL expression was demonstrated. We also found that SIRT1 suppresses PPARgamma
      expression in trophoblasts. Most importantly, inhibition of PPARgamma abolished
      the SIRT1-mediated regulatory effect on LPL expression. Together, these results
      indicate that maternal overnutrition induces LPL expression in trophoblasts by
      reducing the inhibitory effect of SIRT1 on PPARgamma. 

PMID- 25948682
TI  - SIRT3 Is Crucial for Maintaining Skeletal Muscle Insulin Action and Protects
      Against Severe Insulin Resistance in High-Fat-Fed Mice.
AB  - Protein hyperacetylation is associated with glucose intolerance and insulin
      resistance, suggesting that the enzymes regulating the acetylome play a role in
      this pathological process. Sirtuin 3 (SIRT3), the primary mitochondrial
      deacetylase, has been linked to energy homeostasis. Thus, it is hypothesized that
      the dysregulation of the mitochondrial acetylation state, via genetic deletion of
      SIRT3, will amplify the deleterious effects of a high-fat diet (HFD).
      Hyperinsulinemic-euglycemic clamp experiments show, for the first time, that mice
      lacking SIRT3 exhibit increased insulin resistance due to defects in skeletal
      muscle glucose uptake. Permeabilized muscle fibers from HFD-fed SIRT3 knockout
      (KO) mice showed that tricarboxylic acid cycle substrate-based respiration is
      decreased while fatty acid-based respiration is increased, reflecting a fuel
      switch from glucose to fatty acids. Consistent with reduced muscle glucose
      uptake, hexokinase II (HKII) binding to the mitochondria is decreased in muscle
      from HFD-fed SIRT3 KO mice, suggesting decreased HKII activity. These results
      show that the absence of SIRT3 in HFD-fed mice causes profound impairments in
      insulin-stimulated muscle glucose uptake, creating an increased reliance on fatty
      acids. Insulin action was not impaired in the lean SIRT3 KO mice. This suggests
      that SIRT3 protects against dietary insulin resistance by facilitating glucose
      disposal and mitochondrial function. 

PMID- 25948683
TI  - BIM Deficiency Protects NOD Mice From Diabetes by Diverting Thymocytes to
      Regulatory T Cells.
AB  - Because regulatory T-cell (Treg) development can be induced by the same agonist
      self-antigens that induce negative selection, perturbation of apoptosis will
      affect both negative selection and Treg development. But how the processes of
      thymocyte deletion versus Treg differentiation bifurcate and their relative
      importance for tolerance have not been studied in spontaneous organ-specific
      autoimmune disease. We addressed these questions by removing a critical mediator
      of thymocyte deletion, BIM, in the NOD mouse model of autoimmune diabetes.
      Despite substantial defects in the deletion of autoreactive thymocytes, BIM
      deficient NOD (NODBim(-/-)) mice developed less insulitis and were protected from
      diabetes. BIM deficiency did not impair effector T-cell function; however,
      NODBim(-/-) mice had increased numbers of Tregs, including those specific for
      proinsulin, in the thymus and peripheral lymphoid tissues. Increased levels of
      Nur77, CD5, GITR, and phosphorylated IkappaB-alpha in thymocytes from NODBim(-/-)
      mice suggest that autoreactive cells receiving strong T-cell receptor signals
      that would normally delete them escape apoptosis and are diverted into the Treg
      pathway. Paradoxically, in the NOD model, reduced thymic deletion ameliorates
      autoimmune diabetes by increasing Tregs. Thus, modulating apoptosis may be one of
      the ways to increase antigen-specific Tregs and prevent autoimmune disease. 

PMID- 25948685
TI  - The role of biotic forces in driving macroevolution: beyond the Red Queen.
AB  - A multitude of hypotheses claim that abiotic factors are the main drivers of
      macroevolutionary change. By contrast, Van Valen's Red Queen hypothesis is often
      put forward as the sole representative of the view that biotic forcing is the
      main evolutionary driver. This imbalance of hypotheses does not reflect our
      current knowledge: theoretical work demonstrates the plausibility of biotically
      driven long-term evolution, whereas empirical work suggests a central role for
      biotic forcing in macroevolution. We call for a more pluralistic view of how
      biotic forces may drive long-term evolution that is compatible with both
      phenotypic stasis in the fossil record and with non-constant extinction rates.
      Promising avenues of research include contrasting predictions from relevant
      theories within ecology and macroevolution, as well as embracing both abiotic and
      biotic proxies while modelling long-term evolutionary data. By fitting models
      describing hypotheses of biotically driven macroevolution to data, we could
      dissect their predictions and transcend beyond pattern description, possibly
      narrowing the divide between our current understanding of micro- and
      macroevolution. 

PMID- 25948686
TI  - Can the source-sink hypothesis explain macrofaunal abundance patterns in the
      abyss? A modelling test.
AB  - Low food availability is a major structuring force in deep-sea benthic
      communities, sustaining only very low densities of organisms in parts of the
      abyss. These low population densities may result in an Allee effect, whereby
      local reproductive success is inhibited, and populations are maintained by larval
      dispersal from bathyal slopes. This slope-abyss source-sink (SASS) hypothesis
      suggests that the abyssal seafloor constitutes a vast sink habitat with
      macrofaunal populations sustained only by an influx of larval 'refugees' from
      source areas on continental slopes, where higher productivity sustains greater
      population densities. Abyssal macrofaunal population densities would thus be
      directly related to larval inputs from bathyal source populations. We evaluate
      three predictions derived from the SASS hypothesis: (i) slope-derived larvae can
      be passively transported to central abyssal regions within a single larval
      period, (ii) projected larval export from slopes to the abyss reproduces global
      patterns of macrofaunal abundance and (iii) macrofaunal abundance decreases with
      distance from the continental slope. We find that abyssal macrofaunal populations
      are unlikely to be sustained solely through influx of larvae from slope sources.
      Rather, local reproduction probably sustains macrofaunal populations in
      relatively high-productivity abyssal areas, which must also be considered as
      potential larval source areas for more food-poor abyssal regions. 

PMID- 25948684
TI  - Extant primitively segmented spiders have recently diversified from an ancient
      lineage.
AB  - Living fossils are lineages that have retained plesiomorphic traits through long
      time periods. It is expected that such lineages have both originated and
      diversified long ago. Such expectations have recently been challenged in some
      textbook examples of living fossils, notably in extant cycads and coelacanths.
      Using a phylogenetic approach, we tested the patterns of the origin and
      diversification of liphistiid spiders, a clade of spiders considered to be living
      fossils due to their retention of arachnid plesiomorphies and their exclusive
      grouping in Mesothelae, an ancient clade sister to all modern spiders.
      Facilitated by original sampling throughout their Asian range, we here provide
      the phylogenetic framework necessary for reconstructing liphistiid biogeographic
      history. All phylogenetic analyses support the monophyly of Liphistiidae and of
      eight genera. As the fossil evidence supports a Carboniferous Euramerican origin
      of Mesothelae, our dating analyses postulate a long eastward over-land dispersal
      towards the Asian origin of Liphistiidae during the Palaeogene (39-58 Ma).
      Contrary to expectations, diversification within extant liphistiid genera is
      relatively recent, in the Neogene and Late Palaeogene (4-24 Ma). While no over
      water dispersal events are needed to explain their evolutionary history, the
      history of liphistiid spiders has the potential to play prominently in vicariant
      biogeographic studies. 

PMID- 25948687
TI  - Epidemic predictions in an imperfect world: modelling disease spread with partial
      data.
AB  - 'Big-data' epidemic models are being increasingly used to influence government
      policy to help with control and eradication of infectious diseases. In the case
      of livestock, detailed movement records have been used to parametrize realistic
      transmission models. While livestock movement data are readily available in the
      UK and other countries in the EU, in many countries around the world, such
      detailed data are not available. By using a comprehensive database of the UK
      cattle trade network, we implement various sampling strategies to determine the
      quantity of network data required to give accurate epidemiological predictions.
      It is found that by targeting nodes with the highest number of movements,
      accurate predictions on the size and spatial spread of epidemics can be made.
      This work has implications for countries such as the USA, where access to data is
      limited, and developing countries that may lack the resources to collect a full
      dataset on livestock movements. 

PMID- 25948688
TI  - Movements of genes between populations: are pollinators more effective at
      transferring their own or plant genetic markers?
AB  - The transfer of genes between populations is increasingly important in a world
      where pollinators are declining, plant and animal populations are increasingly
      fragmented and climate change is forcing shifts in distribution. The distances
      that pollen can be transported by small insects are impressive, as is the
      extensive gene flow between their own populations. We compared the relative ease
      by which small insects introduce genetic markers into their own and host-plant
      populations. Gene flow via seeds and pollen between populations of an Asian fig
      species were evaluated using cpDNA and nuclear DNA markers, and between
      population gene flow of its pollinator fig wasp was determined using
      microsatellites. This insect is the tree's only pollinator locally, and only
      reproduces in its figs. The plant's pollen-to-seed dispersal ratio was 9.183
      9.437, smaller than that recorded for other Ficus. The relative effectiveness of
      the pollinator at introducing markers into its own populations was higher than
      the rate it introduced markers into the plant's populations (ratio = 14 : 1), but
      given the demographic differences between plant and pollinator, pollen transfer
      effectiveness is remarkably high. Resource availability affects the dispersal of
      fig wasps, and host-plant flowering phenology here and in other plant-pollinator
      systems may strongly influence relative gene flow rates. 

PMID- 25948689
TI  - Oviposition site choice under conflicting risks demonstrates that aquatic
      predators drive terrestrial egg-laying.
AB  - Laying eggs out of water was crucial to the transition to land and has evolved
      repeatedly in multiple animal phyla. However, testing hypotheses about this
      transition has been difficult because extant species only breed in one
      environment. The pantless treefrog, Dendropsophus ebraccatus, makes such tests
      possible because they lay both aquatic and arboreal eggs. Here, we test the
      oviposition site choices of D. ebraccatus under conflicting risks of arboreal egg
      desiccation and aquatic egg predation, thereby estimating the relative importance
      of each selective agent on reproduction. We also measured discrimination between
      habitats with and without predators and development of naturally laid aquatic and
      arboreal eggs. Aquatic embryos in nature developed faster than arboreal embryos,
      implying no cost to aquatic egg laying. In choice tests, D. ebraccatus avoided
      habitats with fish, showing that they can detect aquatic egg predators. Most
      importantly, D. ebraccatus laid most eggs in the water when faced with only
      desiccation risk, but switched to laying eggs arboreally when desiccation risk
      and aquatic predators were both present. This provides the first experimental
      evidence to our knowledge that aquatic predation risk influences non-aquatic
      oviposition and strongly supports the hypothesis that it was a driver of the
      evolution of terrestrial reproduction.

PMID- 25948690
TI  - Predicting abundances of plants and pollinators using a simple compartmental
      mutualistic model.
AB  - Key gaps to be filled in population and community ecology are predicting the
      strength of species interactions and linking pattern with process to understand
      species coexistence and their relative abundances. In the case of mutualistic
      webs, like plant-pollinator networks, advances in understanding species
      abundances are currently limited, mainly owing to the lack of methodological
      tools to deal with the intrinsic complexity of mutualisms. Here, we propose an
      aggregation method leading to a simple compartmental mutualistic population model
      that captures both qualitatively and quantitatively the size-segregated
      populations observed in a Mediterranean community of nectar-producing plant
      species and nectar-searching animal species. We analyse the issue of optimal
      aggregation level and its connection with the trade-off between realism and
      overparametrization. We show that aggregation of both plants and pollinators into
      five size classes or compartments leads to a robust model with only two tunable
      parameters. Moreover, if, in each compartment, (i) the interaction coefficients
      fulfil the condition of weak mutualism and (ii) the mutualism is facultative for
      at least one party of the compartment, then the interactions between different
      compartments are sufficient to guarantee global stability of the equilibrium
      population. 

PMID- 25948693
TI  - Ankle Joint Contact Loads and Displacement With Progressive Syndesmotic Injury.
AB  - BACKGROUND: Ligamentous injuries to the distal tibiofibular syndesmosis are
      predictive of long-term ankle dysfunction. Mild and moderate syndesmotic injuries
      are difficult to stratify, and the impact of syndesmosis injury on the magnitude
      and distribution of forces within the ankle joint during athletic activities is
      unknown. METHODS: Eight below-knee cadaveric specimens were tested in the intact
      state and after sequential sectioning of the following ligaments: anterior
      inferior tibiofibular, anterior deltoid (1 cm), interosseous/transverse (IOL/TL),
      posterior-inferior tibiofibular, and whole deltoid. In each condition, specimens
      were loaded in axial compression to 700 N and then externally rotated to 20 N.m
      torque. RESULTS: During axial loading and external rotation, both the fibula and
      the talus rotated significantly after each ligament sectioning as compared to the
      intact condition. After IOL/TL release, a significant increase in posterior
      translation of the fibula was observed, although no syndesmotic widening was
      observed. Mean tibiotalar contact pressure increased significantly after IOL/TL
      release, and the center of pressure shifted posterolaterally, relative to more
      stable conditions, after IOL/TL release. There were significant increases in mean
      contact pressure and peak pressure along with a reduction in contact area with
      axial loading and external rotation as compared to axial loading alone for all 5
      conditions. CONCLUSION: Significant increases in tibiotalar contact pressures
      occur when external rotation stresses are added to axial loading. Moderate and
      severe injuries are associated with a significant increase in mean contact
      pressure combined with a shift in the center of pressure and rotation of the
      fibula and talus. CLINICAL RELEVANCE: Considerable changes in ankle joint
      kinematics and contact mechanics may explain why moderate syndesmosis injuries
      take longer to heal and are more likely to develop long-term dysfunction and,
      potentially, ankle arthritis.

PMID- 25948692
TI  - Optimal Position of the Heel Following Reconstruction of the Stage II Adult
      Acquired Flatfoot Deformity.
AB  - BACKGROUND: While previous work has demonstrated a linear relationship between
      the amount of medializing calcaneal osteotomy (MCO) and the change in
      radiographic hindfoot alignment following reconstruction, an ideal postoperative
      hindfoot alignment has yet to be reported. The aim of this study was to identify
      an optimal postoperative hindfoot alignment by correlating radiographic alignment
      with patient outcomes. METHODS: Fifty-five feet in 55 patients underwent flatfoot
      reconstruction for stage II adult-acquired flatfoot deformity (AAFD) by 2
      fellowship-trained foot and ankle orthopedic surgeons. Hindfoot alignment was
      determined as previously described by Saltzman and el-Khoury.(23) Changes in pre-
      and postoperative scores in each Foot and Ankle Outcome Score (FAOS) subscale
      were calculated for patients in postoperative hindfoot valgus (>=0 mm valgus, n =
      18), mild varus (>0 to 5 mm varus, n = 17), and moderate varus (>5 mm varus, n =
      20). Analysis of variance and post hoc Tukey's tests were used to compare the
      change in FAOS results between these 3 groups. RESULTS: At 22 months or more
      postoperatively, patients corrected to mild hindfoot varus showed a significantly
      greater improvement in the FAOS Pain subscale compared with patients in valgus (P
      = .04) and the Symptoms subscale compared with patients in moderate varus (P =
      .03). Although mild hindfoot varus did not differ significantly from moderate
      varus or valgus in the other subscales, mild hindfoot varus did not perform worse
      than these alignments in any FAOS subscale. No statistically significant
      correlations between intraoperative MCO slide distances and FAOS subscales were
      found. CONCLUSIONS: Our study indicates that correction of hindfoot alignment to
      between 0 and 5 mm of varus on the hindfoot alignment view (clinically a straight
      heel) following stage II flatfoot reconstruction was associated with the greatest
      improvement in clinical outcomes following hindfoot reconstruction in stage II
      AAFD. LEVEL OF EVIDENCE: Level III, comparative series.

PMID- 25948691
TI  - A conserved genetic mechanism specifies deutocerebral appendage identity in
      insects and arachnids.
AB  - The segmental architecture of the arthropod head is one of the most controversial
      topics in the evolutionary developmental biology of arthropods. The deutocerebral
      (second) segment of the head is putatively homologous across Arthropoda, as
      inferred from the segmental distribution of the tripartite brain and the absence
      of Hox gene expression of this anterior-most, appendage-bearing segment. While
      this homology statement implies a putative common mechanism for differentiation
      of deutocerebral appendages across arthropods, experimental data for
      deutocerebral appendage fate specification are limited to winged insects.
      Mandibulates (hexapods, crustaceans and myriapods) bear a characteristic pair of
      antennae on the deutocerebral segment, whereas chelicerates (e.g. spiders,
      scorpions, harvestmen) bear the eponymous chelicerae. In such hexapods as the
      fruit fly, Drosophila melanogaster, and the cricket, Gryllus bimaculatus,
      cephalic appendages are differentiated from the thoracic appendages (legs) by the
      activity of the appendage patterning gene homothorax (hth). Here we show that
      embryonic RNA interference against hth in the harvestman Phalangium opilio
      results in homeonotic chelicera-to-leg transformations, and also in some cases
      pedipalp-to-leg transformations. In more strongly affected embryos, adjacent
      appendages undergo fusion and/or truncation, and legs display proximal defects,
      suggesting conservation of additional functions of hth in patterning the antero
      posterior and proximo-distal appendage axes. Expression signal of anterior Hox
      genes labial, proboscipedia and Deformed is diminished, but not absent, in hth
      RNAi embryos, consistent with results previously obtained with the insect G.
      bimaculatus. Our results substantiate a deep homology across arthropods of the
      mechanism whereby cephalic appendages are differentiated from locomotory
      appendages. 

PMID- 25948694
TI  - Impact of Diabetes on Outcome of Total Ankle Replacement.
AB  - BACKGROUND: As the incidence of diabetes mellitus (DM) grows, managing patients
      with diabetes and concomitant ankle arthritis poses a challenging clinical
      dilemma. While diabetes is known to be a risk factor for complications relating
      to open reduction and internal fixation of ankle fractures, it is unclear if DM
      is a risk factor for negative outcomes after total ankle replacement (TAR).
      METHODS: We retrospectively identified a consecutive series of 813 primary TARs
      performed between 2002 and November 2013 that had a minimum follow-up of 1 year.
      Within that larger group, we identified 50 patients with DM and used a control
      group without DM for comparison (n = 55). Clinical outcomes including wound
      issues, infection rates, complications, and failure rates were then compared.
      Functional outcomes, including American Orthopaedic Foot & Ankle Society hindfoot
      score, Short Form-36 (SF-36), Short Musculoskeletal Function Assessment, Foot and
      Ankle Disability Index, and visual analog scale, were also compared. Median
      patient follow-up was 2.3 years in the DM group and 3.1 years in the control
      group (P = .239). RESULTS: The body mass index, age, preoperative American
      Society of Anesthesiologists (ASA) grading, and smoking history in the DM were
      significantly higher than in the control group. While 5 patients (10%) in the DM
      group had secondary operations related to the TAR, no patients had a superficial
      or deep infection. Eight patients (14.5%) in the control group had secondary
      operations, including 1 patient who needed a flap. There was no statistical
      differences in secondary operations (P = .562), revisions (P = .604), or failure
      rates (P = .345). For both the diabetes and control groups, all functional
      outcome scores except SF-36 General Health significantly improved at 1 year
      postoperatively; these improvements were maintained at most recent follow-up.
      There was no statistically significant difference between the groups regarding
      functional outcomes except that at 1 year, the magnitude of improvement in SF-36
      General Heath was significantly better in the control group. CONCLUSIONS: Total
      ankle arthroplasty appears to be an effective and safe means for providing pain
      relief and improving function in patients with diabetes and ankle arthritis.
      While patients with DM were heavier and had worse ASA preoperative grades, they
      did not have a significantly different complication or infection rate. LEVEL OF
      EVIDENCE: Level III, retrospective comparative study.

PMID- 25948695
TI  - Asthma-COPD overlap 2015: now we are six.
AB  - BACKGROUND: The overlap between asthma and COPD is increasingly recognised. This
      review examines the new insights, treatment and remaining knowledge gaps for
      asthma-COPD overlap. METHOD: A systematic literature review of cluster analyses
      of asthma and COPD was performed. Articles from 2009 to the present dealing with
      prevalence, morbidity and treatment of asthma-COPD overlap were identified and
      reviewed. RESULTS: Asthma-COPD overlap was consistently recognised in studies
      using a variety of different study designs and sampling. The prevalence was
      approximately 20% in patients with obstructive airways diseases. Asthma-COPD
      overlap was associated with increased morbidity and possibly an increased
      mortality and comorbidity. There was evidence of a heterogeneous pattern of
      airway inflammation that included eosinophilic (in adult asthma), neutrophilic or
      mixed patterns (in severe asthma and COPD). Systemic inflammation was present in
      asthma-COPD overlap and resembled that of COPD. Within asthma-COPD overlap, there
      is evidence of different subgroups, and recognition using bronchodilator
      responsiveness has not been successful. Guidelines generally recommend a serial
      approach to assessment, with treatment recommendations dominated by an asthma
      paradigm. Research is needed into key clinical features that impact outcome,
      mechanisms and treatment approaches in asthma-COPD overlap. Identifying and
      treating disease components by multidimensional assessment shows promise.
      CONCLUSIONS: Asthma-COPD overlap has drawn attention to the significant
      heterogeneity that exists within obstructive airway diseases. It should be
      replaced by novel approaches that identify and manage the components of this
      heterogeneity, such as multidimensional assessment and treatment. Future research
      is needed to test these novel and personalised approaches.

PMID- 25948696
TI  - Cerebral oxygen saturation during pulsatile and non-pulsatile cardiopulmonary
      bypass in patients with carotid stenosis.
AB  - Pulsatile and non-pulsatile cardiopulmonary bypass (CPB) flows may have different
      impact on cerebral oxygen saturation in patients with restricted cerebral
      arterial blood supply. Twenty patients, ten diagnosed with carotid stenosis (CS,
      n = 10) and ten without known carotid disease (Controls, n = 10), were subjected
      to one period of pulsatile and one period of non-pulsatile flow (6-8 min each)
      during CPB at 32 degrees C. Cerebral oxygen saturation was registered by near
      infrared light spectroscopy (NIRS).The mean arterial pressure (MAP) was
      significantly lowered by pulsatile CPB flow. The NIRS tissue oxygenation index
      (TOI) tended to decrease in the CS group and increase in the Controls during
      pulsatile flow compared with non-pulsatile; however, the changes were not
      statistically significant.No significant correlations were seen between the
      changes in MAP and TOI across the observation periods.In conclusion, pulsatile
      CPB flow caused slightly decreased mean arterial pressure while the effect on
      cerebral oxygenation was unclear. Pulsatile flow was not found superior to non
      pulsatile flow in patients with or without carotid stenosis. 

PMID- 25948697
TI  - 'Who's coming up next to do this work?' Generational tensions in accounts of
      providing HIV care in the community.
AB  - Generational change is believed to be transforming the educational and employment
      preferences of medical trainees. In this article, we examine generational
      tensions in interviews with policy leaders and clinicians on workforce issues
      within one subset of the Australian medical profession: general practitioners who
      provide care to people with HIV in community settings. Integrating the accounts
      of policy leaders (n = 24) and clinicians representing the 'first generation' (n
      = 21) and 'next generation' (n = 23) of clinicians to do this work, shared and
      divergent perspectives on the role of generational change in shaping professional
      engagement were revealed. While those engaged in the early response to HIV
      believed younger clinicians to be less interested in the scientific and political
      dimensions of HIV care and more concerned about financial security and life
      balance, the next generation both countered and integrated these beliefs into new
      ways of conceptualising the value and appeal of this field of medicine. Critical
      appraisal of the assumptions that underpin generational discourse is essential in
      appreciating the changing views of providers over time, particularly in fields of
      medicine which have featured significant historical turning points.

PMID- 25948698
TI  - Meaningful use stage 2 e-prescribing threshold and adverse drug events in the
      Medicare Part D population with diabetes.
AB  - Evidence supports the potential for e-prescribing to reduce the incidence of
      adverse drug events (ADEs) in hospital-based studies, but studies in the
      ambulatory setting have not used occurrence of ADE as their outcome. Using the
      "prescription origin code" in 2011 Medicare Part D prescription drug events
      files, the authors investigate whether physicians who meet the meaningful use
      stage 2 threshold for e-prescribing (>=50% of prescriptions e-prescribed) have
      lower rates of ADEs among their diabetic patients. Risk of any patient with
      diabetes in the provider's panel having an ADE from anti-diabetic medications was
      modeled adjusted for prescriber and patient panel characteristics. Physician e
      prescribing to Medicare beneficiaries was associated with reduced risk of ADEs
      among their diabetes patients (Odds Ratio: 0.95; 95% CI, 0.94-0.96), as were
      several prescriber and panel characteristics. However, these physicians treated
      fewer patients from disadvantaged populations. 

PMID- 25948699
TI  - A multilingual gold-standard corpus for biomedical concept recognition: the
      Mantra GSC.
AB  - OBJECTIVE: To create a multilingual gold-standard corpus for biomedical concept
      recognition. MATERIALS AND METHODS: We selected text units from different
      parallel corpora (Medline abstract titles, drug labels, biomedical patent claims)
      in English, French, German, Spanish, and Dutch. Three annotators per language
      independently annotated the biomedical concepts, based on a subset of the Unified
      Medical Language System and covering a wide range of semantic groups. To reduce
      the annotation workload, automatically generated preannotations were provided.
      Individual annotations were automatically harmonized and then adjudicated, and
      cross-language consistency checks were carried out to arrive at the final
      annotations. RESULTS: The number of final annotations was 5530. Inter-annotator
      agreement scores indicate good agreement (median F-score 0.79), and are similar
      to those between individual annotators and the gold standard. The automatically
      generated harmonized annotation set for each language performed equally well as
      the best annotator for that language. DISCUSSION: The use of automatic
      preannotations, harmonized annotations, and parallel corpora helped to keep the
      manual annotation efforts manageable. The inter-annotator agreement scores
      provide a reference standard for gauging the performance of automatic annotation
      techniques. CONCLUSION: To our knowledge, this is the first gold-standard corpus
      for biomedical concept recognition in languages other than English. Other
      distinguishing features are the wide variety of semantic groups that are being
      covered, and the diversity of text genres that were annotated.

PMID- 25948700
TI  - Non-Reflective Thinkers Are Predisposed to Attribute Supernatural Causation to
      Uncanny Experiences.
AB  - For unknown reasons, individuals who are confident in their intuitions are more
      likely to hold supernatural beliefs. How does an intuitive cognitive style lead
      one to believe in faith healing, astrology, or extrasensory perception (ESP)? We
      hypothesize that cognitive style is critically important after one experiences an
      uncanny event that seems to invite a supernatural explanation. In three studies,
      we show that irrespective of their prior beliefs in the supernatural, non
      reflective thinkers are more likely than reflective thinkers to accept
      supernatural causation after an uncanny encounter with astrology and ESP. This is
      the first time that controlled experiments demonstrate the negative dynamics of
      reflection and supernatural causality attribution. We consider the possible
      generalization of our findings to religious beliefs and their implications for
      the social vulnerability of non-reflective individuals. 

PMID- 25948702
TI  - Genome-wide transcriptomic analysis of the effects of sub-ambient atmospheric
      oxygen and elevated atmospheric carbon dioxide levels on gametophytes of the
      moss, Physcomitrella patens.
AB  - It is widely accepted that atmospheric O2 has played a key role in the
      development of life on Earth, as evident from the coincidence between the rise of
      atmospheric O2 concentrations in the Precambrian and biological evolution.
      Additionally, it has also been suggested that low atmospheric O2 is one of the
      major drivers for at least two of the five mass-extinction events in the
      Phanerozoic. At the molecular level, our understanding of the responses of plants
      to sub-ambient O2 concentrations is largely confined to studies of the responses
      of underground organs, e.g. roots to hypoxic conditions. Oxygen deprivation often
      results in elevated CO2 levels, particularly under waterlogged conditions, due to
      slower gas diffusion in water compared to air. In this study, changes in the
      transcriptome of gametophytes of the moss Physcomitrella patens arising from
      exposure to sub-ambient O2 of 13% (oxygen deprivation) and elevated CO2 (1500
      ppmV) were examined to further our understanding of the responses of lower plants
      to changes in atmospheric gaseous composition. Microarray analyses revealed that
      the expression of a large number of genes was affected under elevated CO2 (814
      genes) and sub-ambient O2 conditions (576 genes). Intriguingly, the expression of
      comparatively fewer numbers of genes (411 genes) was affected under a combination
      of both sub-ambient O2 and elevated CO2 condition (low O2-high CO2). Overall, the
      results point towards the effects of atmospheric changes in CO2 and O2 on
      transcriptional reprogramming, photosynthetic regulation, carbon metabolism, and
      stress responses. 

PMID- 25948703
TI  - Solanum lycopersicum IAA15 functions in the 2,4-dichlorophenoxyacetic acid
      herbicide mechanism of action by mediating abscisic acid signalling.
AB  - 2,4-Dichlorophenoxyacetic acid (2,4-D), an important plant growth regulator, is
      the herbicide most commonly used worldwide to control weeds. However, broad-leaf
      fruits and vegetables are extremely sensitive to herbicides, which can cause
      damage and result in lost crops when applied in a manner inconsistent with the
      directions. Despite detailed knowledge of the mechanism of 2,4-D, the regulation
      of auxin signalling is still unclear. For example, although the major mediators
      of auxin signalling, including auxin/indole acetic acid (AUX/IAA) proteins and
      auxin response factors (ARFs), are known to mediate auxinic herbicides, the
      underlying mechanisms are still unclear. In this study, the effects of 2,4-D on
      AUX/IAA gene expression in tomato were investigated, and the two most notably up
      regulated genes, SlIAA15 and SlIAA29, were selected for further study. Western
      blotting revealed the substantial accumulation of both SlIAA15 and SlIAA29, and
      the expression levels of the corresponding genes were increased following
      abscisic acid (ABA) and ethylene treatment. Overexpressing SlIAA15, but not
      SlIAA29, induced a 2,4-D herbicide damage phenotype. The 35S::SlIAA15 line
      exhibited a strong reduction in leaf stomatal density and altered expression of
      some R2R3 MYB genes that are putatively involved in the regulation of stomatal
      differentiation. Further study revealed that root elongation in 35S::SlIAA15 was
      sensitive to ABA treatment, and was most probably due to the altered expression
      of an ABA signal transduction gene. In addition, the altered auxin sensitivities
      of SlIAA15 transformants were also explored. These results suggested that SlIAA15
      plays an important role in determining the effects of the herbicide 2,4-D. 

PMID- 25948704
TI  - AINTEGUMENTA and the D-type cyclin CYCD3;1 independently contribute to petal size
      control in Arabidopsis: evidence for organ size compensation being an emergent
      rather than a determined property.
AB  - Plant lateral aerial organ (LAO) growth is determined by the number and size of
      cells comprising the organ. Genetic alteration of one parameter is often
      accompanied by changes in the other, such that the overall effect on final LAO
      size is minimized, suggested to be caused by an active organ level 'compensation
      mechanism'. For example, the aintegumenta (ant) mutant exhibits reduced cell
      number but increased cell size in LAOs. The ANT transcription factor regulates
      the duration of the cell division phase of LAO growth, and its ectopic expression
      is correlated with increased levels of the cell cycle regulator CYCD3;1. This has
      previously led to the suggestion that ANT regulates CYCD3;1. It is shown here
      that while ANT is required for normal cell proliferation in petals, CYCD3;1 is
      not, suggesting that ANT does not regulate CYCD3;1 during petal growth. Moreover
      CYCD3;1 expression was similar in wild-type and ant-9 flowers. In contrast to the
      compensatory changes between cell size and number in ant mutants, cycd3;1 mutants
      show increased petal cell size unaccompanied by changes in cell number, leading
      to larger organs. However, loss of CYCD3;1 in the ant-9 mutant background leads
      to a phenotype consistent with compensation mechanisms. These apparently
      arbitrary examples of compensation are reconciled through a model of LAO growth
      in which distinct phases of division and cell expansion occupy differing lengths
      of a defined overall growth window. This leads to the proposal that many
      observations of 'compensation mechanisms' might alternatively be more simply
      explained as emergent properties of LAO development. 

PMID- 25948705
TI  - RNA sequencing and functional analysis implicate the regulatory role of long non
      coding RNAs in tomato fruit ripening.
AB  - Recently, long non-coding RNAs (lncRNAs) have been shown to play critical
      regulatory roles in model plants, such as Arabidopsis, rice, and maize. However,
      the presence of lncRNAs and how they function in fleshy fruit ripening are still
      largely unknown because fleshy fruit ripening is not present in the above model
      plants. Tomato is the model system for fruit ripening studies due to its dramatic
      ripening process. To investigate further the role of lncRNAs in fruit ripening,
      it is necessary and urgent to discover and identify novel lncRNAs and understand
      the function of lncRNAs in tomato fruit ripening. Here it is reported that 3679
      lncRNAs were discovered from wild-type tomato and ripening mutant fruit. The
      lncRNAs are transcribed from all tomato chromosomes, 85.1% of which came from
      intergenic regions. Tomato lncRNAs are shorter and have fewer exons than protein
      coding genes, a situation reminiscent of lncRNAs from other model plants. It was
      also observed that 490 lncRNAs were significantly up-regulated in ripening mutant
      fruits, and 187 lncRNAs were down-regulated, indicating that lncRNAs could be
      involved in the regulation of fruit ripening. In line with this, silencing of two
      novel tomato intergenic lncRNAs, lncRNA1459 and lncRNA1840, resulted in an
      obvious delay of ripening of wild-type fruit. Overall, the results indicated that
      lncRNAs might be essential regulators of tomato fruit ripening, which sheds new
      light on the regulation of fruit ripening.

PMID- 25948706
TI  - A G protein alpha null mutation confers prolificacy potential in maize.
AB  - Plasticity in plant development is controlled by environmental signals through
      largely unknown signalling networks. Signalling coupled by the heterotrimeric G
      protein complex underlies various developmental pathways in plants. The
      morphology of two plastic developmental pathways, root system architecture and
      female inflorescence formation, was quantitatively assessed in a mutant compact
      plant 2 (ct2) lacking the alpha subunit of the heterotrimeric G protein complex
      in maize. The ct2 mutant partially compensated for a reduced shoot height by
      increased total leaf number, and had far more ears, even in the presence of
      pollination signals. The maize heterotrimeric G protein complex is important in
      some plastic developmental traits in maize. In particular, the maize Galpha
      subunit is required to dampen the overproduction of female inflorescences. 

PMID- 25948707
TI  - E151 (sym15), a pleiotropic mutant of pea (Pisum sativum L.), displays low nodule
      number, enhanced mycorrhizae, delayed lateral root emergence, and high root
      cytokinin levels.
AB  - In legumes, the formation of rhizobial and mycorrhizal root symbioses is a highly
      regulated process which requires close communication between plant and
      microorganism. Plant mutants that have difficulties establishing symbioses are
      valuable tools for unravelling the mechanisms by which these symbioses are formed
      and regulated. Here E151, a mutant of Pisum sativum cv. Sparkle, was examined to
      characterize its root growth and symbiotic defects. The symbioses in terms of
      colonization intensity, functionality of micro-symbionts, and organ dominance
      were compared between the mutant and wild type. The endogenous cytokinin (CK) and
      abscisic acid (ABA) levels and the effect of the exogenous application of these
      two hormones were determined. E151 was found to be a low and delayed nodulator,
      exhibiting defects in both the epidermal and cortical programmes though a few
      mature and functional nodules develop. Mycorrhizal colonization of E151 was
      intensified, although the fungal functionality was impaired. Furthermore, E151
      displayed an altered lateral root (LR) phenotype compared with that of the wild
      type whereby LR emergence is initially delayed but eventually overcome. No
      differences in ABA levels were found between the mutant and the wild type, but
      non-inoculated E151 exhibited significantly high CK levels. It is hypothesized
      that CK plays an essential role in differentially mediating the entry of the two
      micro-symbionts into the cortex; whereas it would inhibit the entry of the
      rhizobia in that tissue, it would promote that of the fungus. E151 is a
      developmental mutant which may prove to be a useful tool in further understanding
      the role of hormones in the regulation of beneficial root symbioses. 

PMID- 25948708
TI  - Interaction of cold radiofrequency plasma with seeds of beans (Phaseolus
      vulgaris).
AB  - The impact of cold radiofrequency air plasma on the wetting properties and water
      imbibition of beans (Phaseolus vulgaris) was studied. The influence of plasma on
      wetting of a cotyledon and seed coat (testa) was elucidated. It was established
      that cold plasma treatment leads to hydrophilization of the cotyledon and tissues
      constituting the testa when they are separately exposed to plasma. By contrast,
      when the entire bean is exposed to plasma treatment, only the external surface of
      the bean is hydrophilized by the cold plasma. Water imbibition by plasma-treated
      beans was studied. Plasma treatment markedly accelerates the water absorption.
      The crucial role of a micropyle in the process of water imbibition was
      established. It was established that the final percentage of germination was
      almost the same in the cases of plasma-treated, untreated, and vacuum-pumped
      samples. However, the speed of germination was markedly higher for the plasma
      treated samples. The influence of the vacuum pumping involved in the cold plasma
      treatment on the germination was also clarified. 

PMID- 25948709
TI  - Sugarcane for water-limited environments. Variation in stomatal conductance and
      its genetic correlation with crop productivity.
AB  - Stomatal conductance (g(s)) and canopy temperature have been used to estimate
      plant water status in many crops. The behaviour of g(s) in sugarcane indicates
      that the internal leaf water status is controlled by regular opening and closing
      of stomata. A large number of g(s) measurements obtained across varying moisture
      regimes, locations, and crop cycles with a diverse sugarcane germplasm composed
      of introgression, and commercial clones indicated that there is a high genetic
      variation for g(s) that can be exploited in a breeding programme. Regardless of
      the environmental influences on the expression of this trait, moderate
      heritability was observed across 51 sets of individual measurements made on
      replicated trials over 3 years. The clone*water status interaction (G*E)
      variation was smaller than the clone (G) variation on many occasions. A wide
      range of genetic correlations (r(g)= -0.29 to 0.94) between g(s) and yield were
      observed across test environments in all three different production regions used.
      Canopy conductance (g(c)) based on g(s) and leaf area index (LAI) showed a
      stronger genetic correlation than the g(s) with cane yield (tonnes of cane per
      hectare; TCH) at 12 months (mature crop). The regression analysis of input
      weather data for the duration of measurements showed that the predicted values of
      r(g) correlated with the maximum temperature (r=0.47) during the measurements and
      less with other environmental variables. These results confirm that the g(c)
      could have potential as a criterion for early-stage selection of clones in
      sugarcane breeding programmes.

PMID- 25948710
TI  - Peony-Glycyrrhiza Decoction, an Herbal Preparation, Inhibits Clozapine Metabolism
      via Cytochrome P450s, but Not Flavin-Containing Monooxygenase in In Vitro Models.
AB  - Our previous studies have shown the therapeutic efficacy and underlying
      mechanisms of Peony-Glycyrrhiza Decoction (PGD), an herbal preparation, in
      treating antipsychotic-induced hyperprolactinemia in cultured cells, animal
      models, and human subjects. In the present study, we further evaluated
      pharmacokinetic interactions of PGD with clozapine (CLZ) in human liver
      microsomes (HLM), recombinantly expressed cytochrome P450s (P450s), and flavin
      containing monooxygenases (FMOs). CLZ metabolites, N-demethyl-clozapine and
      clozapine-N-oxide, were measured. PGD, individual peony and glycyrrhiza
      preparations, and the two individual preparations in combination reduced
      production of CLZ metabolites to different extents in HLM. While the known
      bioactive constituents of PGD play a relatively minor role in the kinetic effects
      of PGD on P450 activity, PGD as a whole had a weak-to-moderate inhibitory potency
      toward P450s, in particular CYP1A2 and CYP3A4. FMOs are less actively involved in
      mediating CLZ metabolism and the PGD inhibition of CLZ. These results suggest
      that PGD has the capacity to suppress CLZ metabolism in the human liver
      microsomal system. This suppression is principally associated with the inhibition
      of related P450 activity but not FMOs. The present study provides in vitro
      evidence of herb-antipsychotic interactions. 

PMID- 25948711
TI  - Upregulation of UGT2B4 Expression by 3'-Phosphoadenosine-5'-Phosphosulfate
      Synthase Knockdown: Implications for Coordinated Control of Bile Acid
      Conjugation.
AB  - During cholestasis, the bile acid-conjugating enzymes, SULT2A1 and UGT2B4, work
      in concert to prevent the accumulation of toxic bile acids. To understand the
      impact of sulfotransferase deficiency on human hepatic gene expression, we
      knocked down 3'-phosphoadenosine-5'-phosphosulfate synthases (PAPSS) 1 and 2,
      which catalyze synthesis of the obligate sulfotransferase cofactor, in HepG2
      cells. PAPSS knockdown caused no change in SULT2A1 expression; however, UGT2B4
      expression increased markedly (~41-fold increase in UGT2B4 mRNA content).
      Knockdown of SULT2A1 in HepG2 cells also increased UGT2B4 expression. To
      investigate the underlying mechanism, we transfected PAPSS-deficient HepG2 cells
      with a luciferase reporter plasmid containing ~2 Kb of the UGT2B4 5'-flanking
      region, which included a response element for the bile acid-sensing nuclear
      receptor, farnesoid X receptor (FXR). FXR activation or overexpression increased
      UGT2B4 promoter activity; however, knocking down FXR or mutating or deleting the
      FXR response element did not significantly decrease UGT2B4 promoter activity.
      Further evaluation of the UGT2B4 5'-flanking region indicated the presence of
      distal regulatory elements between nucleotides -10090 and -10037 that negatively
      and positively regulated UGT2B4 transcription. Pulse-chase analysis showed that
      increased UGT2B4 expression in PAPSS-deficient cells was attributable to both
      increased mRNA synthesis and stability. Transfection analysis demonstrated that
      the UGT2B4 3'-untranslated region decreased luciferase reporter expression less
      in PAPSS-deficient cells than in control cells. These data indicate that knocking
      down PAPSS increases UGT2B4 transcription and mRNA stability as a compensatory
      response to the loss of SULT2A1 activity, presumably to maintain bile acid
      conjugating activity. 

PMID- 25948712
TI  - Comprehensive Evaluation for Substrate Selectivity of Cynomolgus Monkey
      Cytochrome P450 2C9, a New Efavirenz Oxidase.
AB  - Cynomolgus monkeys are widely used as primate models in preclinical studies,
      because of their evolutionary closeness to humans. In humans, the cytochrome P450
      (P450) 2C enzymes are important drug-metabolizing enzymes and highly expressed in
      livers. The CYP2C enzymes, including CYP2C9, are also expressed abundantly in
      cynomolgus monkey liver and metabolize some endogenous and exogenous substances
      like testosterone, S-mephenytoin, and diclofenac. However, comprehensive
      evaluation regarding substrate specificity of monkey CYP2C9 has not been
      conducted. In the present study, 89 commercially available drugs were examined to
      find potential monkey CYP2C9 substrates. Among the compounds screened, 20 drugs
      were metabolized by monkey CYP2C9 at a relatively high rates. Seventeen of these
      compounds were substrates or inhibitors of human CYP2C9 or CYP2C19, whereas three
      drugs were not, indicating that substrate specificity of monkey CYP2C9 resembled
      those of human CYP2C9 or CYP2C19, with some differences in substrate
      specificities. Although efavirenz is known as a marker substrate for human
      CYP2B6, efavirenz was not oxidized by CYP2B6 but by CYP2C9 in monkeys. Liquid
      chromatography-mass spectrometry analysis revealed that monkey CYP2C9 and human
      CYP2B6 formed the same mono- and di-oxidized metabolites of efavirenz at 8 and 14
      positions. These results suggest that the efavirenz 8-oxidation could be one of
      the selective markers for cynomolgus monkey CYP2C9 among the major three CYP2C
      enzymes tested. Therefore, monkey CYP2C9 has the possibility of contributing to
      limited specific differences in drug oxidative metabolism between cynomolgus
      monkeys and humans. 

PMID- 25948713
TI  - Pictorial cigarette pack warnings: a meta-analysis of experimental studies.
AB  - OBJECTIVE: To inform international research and policy, we conducted a meta
      analysis of the experimental literature on pictorial cigarette pack warnings.
      DATA SOURCES: We systematically searched 7 computerised databases in April 2013
      using several search terms. We also searched reference lists of relevant
      articles. STUDY SELECTION: We included studies that used an experimental protocol
      to test cigarette pack warnings and reported data on both pictorial and text-only
      conditions. 37 studies with data on 48 independent samples (N=33,613) met
      criteria. DATA EXTRACTION AND SYNTHESIS: Two independent coders coded all study
      characteristics. Effect sizes were computed from data extracted from study
      reports and were combined using random effects meta-analytic procedures. RESULTS:
      Pictorial warnings were more effective than text-only warnings for 12 of 17
      effectiveness outcomes (all p<0.05). Relative to text-only warnings, pictorial
      warnings (1) attracted and held attention better; (2) garnered stronger cognitive
      and emotional reactions; (3) elicited more negative pack attitudes and negative
      smoking attitudes and (4) more effectively increased intentions to not start
      smoking and to quit smoking. Participants also perceived pictorial warnings as
      being more effective than text-only warnings across all 8 perceived effectiveness
      outcomes. CONCLUSIONS: The evidence from this international body of literature
      supports pictorial cigarette pack warnings as more effective than text-only
      warnings. Gaps in the literature include a lack of assessment of smoking
      behaviour and a dearth of theory-based research on how warnings exert their
      effects.

PMID- 25948714
TI  - NAIL, a software toolset for inferring, analyzing and visualizing regulatory
      networks.

PMID- 25948716
TI  - pez: phylogenetics for the environmental sciences.
AB  - pez is an R package that permits measurement, modelling and simulation of
      phylogenetic structure in ecological data. pez contains the first implementation
      of many methods in R, and aggregates existing data structures and methods into a
      single, coherent package. AVAILABILITY AND IMPLEMENTATION: pez is released under
      the GPL v3 open-source license, available on the Internet from CRAN
      (http://cran.r-project.org). The package is under active development, and the
      authors welcome contributions (see http://github.com/willpearse/pez). CONTACT:
      will.pearse@gmail.com.

PMID- 25948717
TI  - Neuropsychological effects of levetiracetam and carbamazepine in children with
      focal epilepsy.
AB  - OBJECTIVE: To prospectively evaluate the neuropsychological effect of
      levetiracetam (LVT) in comparison with carbamazepine (CBZ) and its efficacy and
      tolerability as a monotherapy in children with focal epilepsy. METHODS: A total
      of 121 out of 135 screened children (4-16 years) were randomly assigned to LVT or
      CBZ groups in a multicenter, parallel-group, open-label trial. The study's
      primary endpoints were defined as the end of 52 weeks of treatment, followed by
      analysis of changes observed in a series of follow-up neurocognitive, behavioral,
      and emotional function tests performed during treatment in the per protocol
      population. Drug efficacy and tolerability were also analyzed among the intention
      to-treat (ITT) population (ClinicalTrials.gov, number NCT02208492). RESULTS:
      Eighty-one patients (41 LVT, 40 CBZ) from the randomly assigned ITT population of
      121 children (57 LVT, 64 CBZ) were followed up to their last visit. No
      significant worsening or differences were noted between groups in
      neuropsychological tests, except for the Children's Depression Inventory (LVT 
      1.97 vs CBZ +1.43, p = 0.027, [+] improvement of function). LVT-treated patients
      showed an improvement (p = 0.004) in internalizing behavioral problems on the
      Korean Child Behavior Checklist. Seizure-free outcomes were not different between
      the 2 groups (CBZ 57.8% vs LVT 66.7%, p = 0.317). CONCLUSIONS: Neither LVT nor
      CBZ adversely affected neuropsychological function in pediatric patients. Both
      medications were considered equally safe and effective as monotherapy in children
      with focal epilepsy. CLASSIFICATION OF EVIDENCE: This study provides Class II
      evidence that in patients with pediatric focal epilepsy, LVT and CBZ exhibit
      equivalent effects on neuropsychological function.

PMID- 25948718
TI  - Homozygous carriers of APP A713T mutation in an autosomal dominant Alzheimer
      disease family.
AB  - OBJECTIVE: To report, for the first time, a large autosomal dominant Alzheimer
      disease (AD) family in which the APP A713T mutation is present in the homozygous
      and heterozygous state. To date, the mutation has been reported as dominant, and
      in the heterozygous state associated with familial AD and cerebrovascular
      lesions. METHODS: The family described here has been genealogically reconstructed
      over 6 generations dating back to the 19th century. Plasma beta-amyloid peptide
      was measured. Sequencing of causative AD genes was performed. RESULTS: Twenty-one
      individuals, all but 1 born from 2 consanguineous unions, were studied: 8 were
      described as affected through history, 5 were studied clinically and genetically,
      and 8 were asymptomatic at-risk subjects. The A713T mutation was detected in the
      homozygous state in 3 patients and in the heterozygous state in 8 subjects (6
      asymptomatic and 2 affected). CONCLUSIONS: Our findings, also supported by the
      beta-amyloid plasma assay, confirm (1) the pathogenic role of the APP A713T
      mutation, (2) the specific phenotype (AD with cerebrovascular lesions) associated
      with this mutation, and (3) the large span of age at onset, not influenced by
      APOE, TOMM40, and TREM2 genes. No substantial differences concerning clinical
      phenotype were evidenced between heterozygous and homozygous patients, in line
      with the classic definition of dominance. Therefore, in this study, AD followed
      the classic definition of a dominant disease, contrary to that reported in a
      previously described AD family with recessive APP mutation. This confirms that
      genetic AD may be considered a disease with dominant and recessive traits of
      inheritance.

PMID- 25948719
TI  - Severe TK2 enzyme activity deficiency in patients with mild forms of myopathy.

PMID- 25948720
TI  - Healthy eating and reduced risk of cognitive decline: A cohort from 40 countries.
AB  - OBJECTIVE: We sought to determine the association of dietary factors and risk of
      cognitive decline in a population at high risk of cardiovascular disease.
      METHODS: Baseline dietary intake and measures of the Mini-Mental State
      Examination were recorded in 27,860 men and women who were enrolled in 2
      international parallel trials of the ONTARGET (Ongoing Telmisartan Alone and in
      Combination with Ramipril Global Endpoint Trial) and TRANSCEND (Telmisartan
      Randomised Assessment Study in ACE Intolerant Subjects with Cardiovascular
      Disease) studies. We measured diet quality using the modified Alternative Healthy
      Eating Index. Cox proportional hazards regression was used to determine the
      association between diet quality and risk of >=3-point decline in Mini-Mental
      State Examination score, and reported as hazard ratio with 95% confidence
      intervals with adjustment for covariates. RESULTS: During 56 months of follow-up,
      4,699 cases of cognitive decline occurred. We observed lower risk of cognitive
      decline among those in the healthiest dietary quintile of modified Alternative
      Healthy Eating Index compared with lowest quintile (hazard ratio 0.76, 95%
      confidence interval 0.66-0.86, Q5 vs Q1). Lower risk of cognitive decline was
      consistent regardless of baseline cognitive level. CONCLUSION: We found that
      higher diet quality was associated with a reduced risk of cognitive decline.
      Improved diet quality represents an important potential target for reducing the
      global burden of cognitive decline.

PMID- 25948721
TI  - Diabetes: A risk factor for cognitive impairment and dementia?

PMID- 25948722
TI  - Triptan-induced disruption of trigemino-cortical connectivity.
AB  - OBJECTIVE: The 5-HT1B/D agonists (triptans) are specific headache medications
      that have no effect on pain as such. Although they are routinely used in the
      treatment of acute migraine attacks, the underlying mechanisms of action are
      still a matter of debate. METHODS: Forty-three healthy participants underwent
      fMRI while receiving trigemino-nociceptive stimulation and control stimuli in a
      standardized fMRI paradigm. Using a crossover, double-blind, placebo-controlled
      design, 21 participants (10 women, mean age 26.9, range 20-37 years) received
      sumatriptan and 22 participants (11 women, mean age 25.5, range 22-32 years)
      received acetylsalicylic acid (ASA). Administration of medication and saline was
      randomized between participants of each group resulting in half of the
      participants receiving saline and the other half receiving the respective
      medication during the first fMRI data acquisition. RESULTS: While mean pain
      intensity ratings did not differ significantly between control and medication nor
      between medications, we found a significant blood oxygen level-dependent signal
      increase in the trigeminal nuclei and the thalamus after sumatriptan treatment
      compared with placebo or ASA. In addition, we specifically looked for the
      pharmacologic modulation of functional coupling between trigeminal nuclei and
      higher brain areas, i.e., trigemino-cortical pathways, and found a strong
      coupling during the saline condition, which was altered by sumatriptan but not
      after ASA administration. CONCLUSION: These data suggest that a specific
      functional inhibition of trigemino-cortical projections is one of the reasons
      that triptans, unlike pain killers, act highly specifically on headache and
      migraine but not pain as such.

PMID- 25948723
TI  - Understanding the comparative effectiveness of treatment in pediatric epilepsy:
      Call to action.

PMID- 25948724
TI  - Comment: How do triptans work in migraine?

PMID- 25948725
TI  - Glucose indices are associated with cognitive and structural brain measures in
      young adults.
AB  - OBJECTIVE: To evaluate the possible early consequences of impaired glucose
      metabolism on the brain by assessing the relationship of diabetes, fasting blood
      glucose (FBG) levels, and insulin resistance with cognitive performance and brain
      integrity in healthy young and middle-aged adults. METHODS: The sample included
      dementia-free participants (mean age 40 +/- 9 years; 53% women) of the Framingham
      Heart Study third-generation cohort with cognitive testing of memory, abstract
      reasoning, visual perception, attention, and executive function (n = 2,126). In
      addition, brain MRI examination (n = 1,597) was used to determine white matter,
      gray matter, and white matter hyperintensity (WMH) volumes and fractional
      anisotropy measures. We used linear regression models to assess relationships
      between diabetes, FBG, and insulin resistance with cognition, lobar gray matter,
      and WMH volumes as well as voxel-based microstructural white matter integrity and
      gray matter density, adjusting for potential confounders. Mediating effect of
      brain lesions on the association of diabetes with cognitive performance was also
      tested. RESULTS: Diabetes was associated with worse memory, visual perception,
      and attention performance; increased WMH; and decreased total cerebral brain and
      occipital lobar gray matter volumes. The link of diabetes with attention and
      memory was mediated through occipital and frontal atrophy, and the latter also
      through hippocampal atrophy. Both diabetes and increased FBG were associated with
      large areas of reductions in gray matter density and fractional anisotropy on
      voxel-based analyses. CONCLUSIONS: We found that hyperglycemia is associated with
      subtle brain injury and impaired attention and memory even in young adults,
      indicating that brain injury is an early manifestation of impaired glucose
      metabolism.

PMID- 25948726
TI  - Epilepsy after aneurysmal subarachnoid hemorrhage: A population-based, long-term
      follow-up study.
AB  - OBJECTIVE: The aim was to elucidate the incidence and risk factors of epilepsy
      after subarachnoid hemorrhage (SAH) from saccular intracranial aneurysm (sIA) in
      a population-based cohort. METHODS: The Kuopio sIA Database (www.uef.fi/ns)
      includes all unruptured and ruptured sIA cases admitted to the Kuopio University
      Hospital from its defined catchment population in Eastern Finland. The use of
      prescribed medicines, including reimbursable antiepileptic drugs, has been
      entered from the Finnish national registries. The cumulative incidence and
      independent risk factors of epilepsy and death were analyzed in 876 patients with
      sIA-SAH admitted from 1995 to 2007. The competing risks analysis was used to
      correctly estimate the probability of epilepsy, because epilepsy and death after
      sIA-SAH may share risk factors. RESULTS: The follow-up ended at death (n = 200)
      or December 31, 2008; median follow-up time was 76 months. Epilepsy was diagnosed
      in 113 patients in a median of 8 months after sIA-SAH. Cumulative incidence of
      epilepsy after sIA-SAH was 8% at 1 year and 12% at 5 years. Thirty-three percent
      of patients with intracerebral hemorrhage (ICH) >15 cm(3) developed epilepsy. In
      the 876 patients with sIA-SAH, the independent risk factors for epilepsy were ICH
      >15 cm(3), Hunt and Hess grade III-V, and acute seizures. CONCLUSIONS: Cumulative
      incidence of epilepsy is 12% at 5 years. Epilepsy and 12-month mortality after
      sIA-SAH share poor Hunt and Hess grading as an independent risk factor. Epilepsy
      in the 2-week survivors of sIA-SAH is predicted by signs of primary injury in the
      brain tissue, most notably ICH.

PMID- 25948727
TI  - Cyclosporine in acute ischemic stroke.
AB  - OBJECTIVES: We examined whether IV administration of cyclosporine in combination
      with thrombolysis might reduce cerebral infarct size. METHODS: Patients aged 18
      to 85 years, presenting with an anterior-circulation stroke and eligible for
      thrombolytic therapy, were enrolled in this multicenter, single-blinded,
      controlled trial. Fifteen minutes after randomization, patients received either
      an IV bolus injection of 2.0 mg/kg cyclosporine (Sandimmune, Novartis) or
      placebo. The primary endpoint was infarct volume on MRI at 30 days. Secondary
      endpoints included infarct volume according to the site (proximal/distal) of
      arterial occlusion and recanalization after thrombolysis. RESULTS: From October
      2009 to July 2013, 127 patients were enrolled. The primary endpoint was assessed
      in 110 of 127 patients. The reduction of infarct volume in the cyclosporine
      compared with the control group was overall not significant (21.8 mL
      [interquartile range, IQR 5.1, 69.2 mL] vs 28.8 mL [IQR 7.7, 95.0 mL],
      respectively; p = 0.18). However, in patients with proximal occlusion and
      effective recanalization, infarct volume was significantly reduced in the
      cyclosporine compared with the control group (14.9 mL [IQR 1.3, 23.2 mL] vs 48.3
      mL [IQR 34.5, 118.2 mL], respectively; p = 0.009). CONCLUSIONS: Cyclosporine was
      generally not effective in reducing infarct size. However, a smaller infarct size
      was observed in patients with proximal cerebral artery occlusion and efficient
      recanalization. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence
      that in patients with an acute anterior-circulation stroke, thrombolysis plus IV
      cyclosporine does not significantly decrease 30-day MRI infarct volume compared
      with thrombolysis alone.

PMID- 25948728
TI  - Climbing fiber synaptic changes correlate with clinical features in essential
      tremor.

PMID- 25948730
TI  - Status epilepticus: For what are we waiting?

PMID- 25948729
TI  - Time from convulsive status epilepticus onset to anticonvulsant administration in
      children.
AB  - OBJECTIVE: To describe the time elapsed from onset of pediatric convulsive status
      epilepticus (SE) to administration of antiepileptic drug (AED). METHODS: This was
      a prospective observational cohort study performed from June 2011 to June 2013.
      Pediatric patients (1 month-21 years) with convulsive SE were enrolled. In order
      to study timing of AED administration during all stages of SE, we restricted our
      study population to patients who failed 2 or more AED classes or needed
      continuous infusions to terminate convulsive SE. RESULTS: We enrolled 81 patients
      (44 male) with a median age of 3.6 years. The first, second, and third AED doses
      were administered at a median (p25-p75) time of 28 (6-67) minutes, 40 (20-85)
      minutes, and 59 (30-120) minutes after SE onset. Considering AED classes, the
      initial AED was a benzodiazepine in 78 (96.3%) patients and 2 (2-3) doses of
      benzodiazepines were administered before switching to nonbenzodiazepine AEDs. The
      first and second doses of nonbenzodiazepine AEDs were administered at 69 (40-120)
      minutes and 120 (75-296) minutes. In the 64 patients with out-of-hospital SE
      onset, 40 (62.5%) patients did not receive any AED before hospital arrival. In
      the hospital setting, the first and second in-hospital AED doses were given at 8
      (5-15) minutes and 16 (10-40) minutes after SE onset (for patients with in
      hospital SE onset) or after hospital arrival (for patients with out-of-hospital
      SE onset). CONCLUSIONS: The time elapsed from SE onset to AED administration and
      escalation from one class of AED to another is delayed, both in the prehospital
      and in-hospital settings.

PMID- 25948732
TI  - Bladder function in mice with inducible smooth muscle-specific deletion of the
      manganese superoxide dismutase gene.
AB  - Manganese superoxide dismutase (MnSOD) is considered a critical component of the
      antioxidant systems that protect against oxidative damage. We are interested in
      the role of oxidative stress in bladder detrusor smooth muscle (SM) in different
      disease states. In this study, we generated an inducible, SM-specific Sod2(-/-)
      mouse model to investigate the effects of MnSOD depletion on the function of the
      bladder. We crossbred floxed Sod2 (Sod2(lox/lox)) mice with mice containing
      heterozygous knock-in of a gene encoding a tamoxifen-activated Cre recombinase in
      the SM22alpha promoter locus [SM-CreER(T2)(ki)(Cre/+)]. We obtained
      Sod2(lox/lox),SM-CreER(T2)(ki)(Cre/+) mice and injected 8-wk-old males with 4
      hydroxytamoxifen to induce Cre-mediated excision of the floxed Sod2 allele.
      Twelve weeks later, SM-specific deletion of Sod2 and depletion of MnSOD were
      confirmed by polymerase chain reaction, immunoblotting, and immunohistochemistry.
      SM-specific Sod2(-/-) mice exhibited normal growth with no gross abnormalities. A
      significant increase in nitrotyrosine concentration was found in bladder SM
      tissue of SM-specific Sod2(-/-) mice compared with both wild-type mice and
      Sod2(+/+), SM-CreER(T2)(ki)(Cre/+) mice treated with 4-hydroxytamoxifen.
      Assessment of 24-h micturition in SM-specific Sod2(-/-) mice revealed
      significantly higher voiding frequency compared with both wild-type and SM
      specific Cre controls. Conscious cystometry revealed significantly shorter
      intercontraction intervals and lower functional bladder capacity in SM-specific
      Sod2(-/-) mice compared with wild-type mice. This novel model can be used for
      exploring the mechanistic role of oxidative stress in organs rich in SM in
      different pathological conditions. 

PMID- 25948731
TI  - Novel mechanism of hydrogen sulfide-induced guinea pig urinary bladder smooth
      muscle contraction: role of BK channels and cholinergic neurotransmission.
AB  - Hydrogen sulfide (H2S) is a key signaling molecule regulating important
      physiological processes, including smooth muscle function. However, the
      mechanisms underlying H2S-induced detrusor smooth muscle (DSM) contractions are
      not well understood. This study investigates the cellular and tissue mechanisms
      by which H2S regulates DSM contractility, excitatory neurotransmission, and large
      conductance voltage- and Ca(2+)-activated K(+) (BK) channels in freshly isolated
      guinea pig DSM. We used a multidisciplinary experimental approach including
      isometric DSM tension recordings, colorimetric ACh measurement, Ca(2+) imaging,
      and patch-clamp electrophysiology. In isolated DSM strips, the novel slow release
      H2S donor, P-(4-methoxyphenyl)-p-4-morpholinylphosphinodithioic acid morpholine
      salt (GYY4137), significantly increased the spontaneous phasic and nerve-evoked
      DSM contractions. The blockade of neuronal voltage-gated Na(+) channels or
      muscarinic ACh receptors with tetrodotoxin or atropine, respectively, reduced the
      stimulatory effect of GYY4137 on DSM contractility. GYY4137 increased ACh release
      from bladder nerves, which was inhibited upon blockade of L-type voltage-gated
      Ca(2+) channels with nifedipine. Furthermore, GYY4137 increased the amplitude of
      the Ca(2+) transients and basal Ca(2+) levels in isolated DSM strips. GYY4137
      reduced the DSM relaxation induced by the BK channel opener, NS11021. In freshly
      isolated DSM cells, GYY4137 decreased the amplitude and frequency of transient BK
      currents recorded in a perforated whole cell configuration and reduced the single
      BK channel open probability measured in excised inside-out patches. GYY4137
      inhibited spontaneous transient hyperpolarizations and depolarized the DSM cell
      membrane potential. Our results reveal the novel findings that H2S increases
      spontaneous phasic and nerve-evoked DSM contractions by activating ACh release
      from bladder nerves in combination with a direct inhibition of DSM BK channels. 

PMID- 25948733
TI  - Hydrogen sulfide promotes calcium uptake in larval zebrafish.
AB  - Hydrogen sulfide (H2S) can act as a signaling molecule for various ion channels
      and/or transporters; however, little is known about its potential involvement in
      Ca(2+) balance. Using developing zebrafish (Danio rerio) as an in vivo model
      system, the present study demonstrated that acute exposure to H2S donors
      increased Ca(2+) influx at 4 days postfertilization, while chronic (3-day)
      exposure caused a rise in whole body Ca(2+) levels. The mRNA expression of Ca(2+)
      transport-related genes was unaffected by H2S exposure, suggesting that
      posttranscriptional modifications were responsible for the altered rates of
      Ca(2+) uptake. Indeed, treatment of fish with the protein kinase A inhibitor H-89
      abolished the H2S-mediated stimulation of Ca(2+) influx, suggesting that H2S
      increased Ca(2+) influx by activating cAMP-protein kinase A pathways.
      Cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE) are two key
      enzymes in the endogenous synthesis of H2S. Using an antisense morpholino
      knockdown approach, we demonstrated that Ca(2+) influx was reduced in CBS isoform
      b (CBSb)- but not in CSE-deficient fish. Interestingly, the reduction in Ca(2+)
      influx in CBSb-deficient fish was observed only in fish that were acclimated to
      low-Ca(2+) water (i.e., 25 MUM Ca(2+); control: 250 MUM Ca(2+)). Similarly, mRNA
      expression of cbsb but not cse was increased in fish acclimated to low-Ca(2+)
      water. Results from whole-mount immunohistochemistry further revealed that CBSb
      was expressed in Na(+)-K(+)-ATPase-rich cells, which are implicated in Ca(2+)
      uptake in zebrafish larvae. Collectively, the present study suggests a novel role
      for H2S in promoting Ca(2+) influx, particularly in a low-Ca(2+) environment. 

PMID- 25948734
TI  - Histamine activates p38 MAP kinase and alters local lamellipodia dynamics,
      reducing endothelial barrier integrity and eliciting central movement of actin
      fibers.
AB  - The role of the actin cytoskeleton in endothelial barrier function has been
      debated for nearly four decades. Our previous investigation revealed spontaneous
      local lamellipodia in confluent endothelial monolayers that appear to increase
      overlap at intercellular junctions. We tested the hypothesis that the barrier
      disrupting agent histamine would reduce local lamellipodia protrusions and
      investigated the potential involvement of p38 mitogen-activated protein (MAP)
      kinase activation and actin stress fiber formation. Confluent monolayers of human
      umbilical vein endothelial cells (HUVEC) expressing green fluorescent protein
      actin were studied using time-lapse fluorescence microscopy. The protrusion and
      withdrawal characteristics of local lamellipodia were assessed before and after
      addition of histamine. Changes in barrier function were determined using
      electrical cell-substrate impedance sensing. Histamine initially decreased
      barrier function, lamellipodia protrusion frequency, and lamellipodia protrusion
      distance. A longer time for lamellipodia withdrawal and reduced withdrawal
      distance and velocity accompanied barrier recovery. After barrier recovery, a
      significant number of cortical fibers migrated centrally, eventually resembling
      actin stress fibers. The p38 MAP kinase inhibitor SB203580 attenuated the
      histamine-induced decreases in barrier function and lamellipodia protrusion
      frequency. SB203580 also inhibited the histamine-induced decreases in withdrawal
      distance and velocity, and the subsequent actin fiber migration. These data
      suggest that histamine can reduce local lamellipodia protrusion activity through
      activation of p38 MAP kinase. The findings also suggest that local lamellipodia
      have a role in maintaining endothelial barrier integrity. Furthermore, we provide
      evidence that actin stress fiber formation may be a reaction to, rather than a
      cause of, reduced endothelial barrier integrity. 

PMID- 25948736
TI  - Shooting vascular oxidative stress: new hopes for stroke patients?

PMID- 25948735
TI  - Tumor necrosis factor-alpha induces a biphasic change in claudin-2 expression in
      tubular epithelial cells: role in barrier functions.
AB  - The inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) is a pathogenic
      factor in acute and chronic kidney disease. TNF-alpha is known to alter
      expression of epithelial tight junction (TJ) proteins; however, the underlying
      mechanisms and the impact of this effect on epithelial functions remain poorly
      defined. Here we describe a novel biphasic effect of TNF-alpha on TJ protein
      expression. In LLC-PK1 tubular cells, short-term (1-6 h) TNF-alpha treatment
      selectively elevated the expression of the channel-forming TJ protein claudin-2.
      In contrast, prolonged (>8 h) TNF-alpha treatment caused a marked downregulation
      in claudin-2 and an increase in claudin-1, -4, and -7. The early increase and the
      late decrease in claudin-2 expression involved distinct mechanisms. TNF-alpha
      slowed claudin-2 degradation through ERK, causing the early increase. This
      increase was also mediated by the EGF receptor and RhoA and Rho kinase. In
      contrast, prolonged TNF-alpha treatment reduced claudin-2 mRNA levels and
      promoter activity independent from these signaling pathways. Electric Cell
      substrate Impedance Sensing measurements revealed that TNF-alpha also exerted a
      biphasic effect on transepithelial resistance (TER) with an initial decrease and
      a late increase. Thus there was a good temporal correlation between TNF-alpha
      induced claudin-2 protein and TER changes. Indeed, silencing experiments showed
      that the late TER increase was at least in part caused by reduced claudin-2
      expression. Surprisingly, however, claudin-2 silencing did not prevent the early
      TER drop. Taken together, the TNF-alpha-induced changes in claudin-2 levels might
      contribute to TER changes and could also play a role in newly described functions
      of claudin-2 such as proliferation regulation. 

PMID- 25948737
TI  - Gender differences in the effect of cardiovascular drugs: a position document of
      the Working Group on Pharmacology and Drug Therapy of the ESC.

PMID- 25948738
TI  - Regulation of Latent Membrane Protein 1 Signaling through Interaction with
      Cytoskeletal Proteins.
AB  - Latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) induces constitutive
      signaling in EBV-infected cells to ensure the survival of the latently infected
      cells. LMP1 is localized to lipid raft domains to induce signaling. In the
      present study, a genome-wide screen based on bimolecular fluorescence
      complementation (BiFC) was performed to identify LMP1-binding proteins. Several
      actin cytoskeleton-associated proteins were identified in the screen.
      Overexpression of these proteins affected LMP1-induced signaling. BiFC between
      the identified proteins and LMP1 was localized to lipid raft domains and was
      dependent on LMP1-induced signaling. Proximity biotinylation assays with LMP1
      induced biotinylation of the actin-associated proteins, which were shifted in
      molecular mass. Together, the findings of this study suggest that the association
      of LMP1 with lipid rafts is mediated at least in part through interactions with
      the actin cytoskeleton. IMPORTANCE: LMP1 signaling requires oligomerization,
      lipid raft partitioning, and binding to cellular adaptors. The current study
      utilized a genome-wide screen to identify several actin-associated proteins as
      candidate LMP1-binding proteins. The interaction between LMP1 and these proteins
      was localized to lipid rafts and dependent on LMP1 signaling. This suggests that
      the association of LMP1 with lipid rafts is mediated through interactions with
      actin-associated proteins.

PMID- 25948739
TI  - K1 and K15 of Kaposi's Sarcoma-Associated Herpesvirus Are Partial Functional
      Homologues of Latent Membrane Protein 2A of Epstein-Barr Virus.
AB  - The human herpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated
      herpesvirus (KSHV) are associated with Hodgkin's lymphoma (HL) and Primary
      effusion lymphomas (PEL), respectively, which are B cell malignancies that
      originate from germinal center B cells. PEL cells but also a quarter of EBV
      positive HL tumor cells do not express the genuine B cell receptor (BCR), a
      situation incompatible with survival of normal B cells. EBV encodes LMP2A, one of
      EBV's viral latent membrane proteins, which likely replaces the BCR's survival
      signaling in HL. Whether KSHV encodes a viral BCR mimic that contributes to
      oncogenesis is not known because an experimental model of KSHV-mediated B cell
      transformation is lacking. We addressed this uncertainty with mutant EBVs
      encoding the KSHV genes K1 or K15 in lieu of LMP2A and infected primary BCR
      negative (BCR(-)) human B cells with them. We confirmed that the survival of BCR(
      ) B cells and their proliferation depended on an active LMP2A signal. Like LMP2A,
      the expression of K1 and K15 led to the survival of BCR(-) B cells prone to
      apoptosis, supported their proliferation, and regulated a similar set of cellular
      target genes. K1 and K15 encoded proteins appear to have noncomplementing,
      redundant functions in this model, but our findings suggest that both KSHV
      proteins can replace LMP2A's key activities contributing to the survival,
      activation and proliferation of BCR(-) PEL cells in vivo. IMPORTANCE: Several
      herpesviruses encode oncogenes that are receptor-like proteins. Often, they are
      constitutively active providing important functions to the latently infected
      cells. LMP2A of Epstein-Barr virus (EBV) is such a receptor that mimics an
      activated B cell receptor, BCR. K1 and K15, related receptors of Kaposi's sarcoma
      associated herpesvirus (KSHV) expressed in virus-associated tumors, have less
      obvious functions. We found in infection experiments that both viral receptors of
      KSHV can replace LMP2A and deliver functions similar to the endogenous BCR. K1,
      K15, and LMP2A also control the expression of a related set of cellular genes in
      primary human B cells, the target cells of EBV and KSHV. The observed phenotypes,
      as well as the known characteristics of these genes, argue for their
      contributions to cellular survival, B cell activation, and proliferation. Our
      findings provide one possible explanation for the tumorigenicity of KSHV, which
      poses a severe problem in immunocompromised patients.

PMID- 25948741
TI  - MAVS Coordination of Antiviral Innate Immunity.
AB  - RNA virus infection is sensed in the cytoplasm by the retinoic acid-inducible
      gene I (RIG-I)-like receptors. These proteins signal through the host adaptor
      protein MAVS to trigger the antiviral innate immune response. Here, we describe
      how MAVS subcellular localization impacts its function and the regulation
      underlying MAVS signaling. We propose a model to describe how the coordination of
      MAVS functions at the interface between the mitochondria and the mitochondrion
      associated endoplasmic reticulum (ER) membrane programs antiviral signaling. 

PMID- 25948740
TI  - Rift Valley Fever Virus MP-12 Vaccine Is Fully Attenuated by a Combination of
      Partial Attenuations in the S, M, and L Segments.
AB  - Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa
      and characterized by a high rate of abortion in ruminants and hemorrhagic fever,
      encephalitis, or blindness in humans. RVF is caused by Rift Valley fever virus
      (RVFV; family Bunyaviridae, genus Phlebovirus), which has a tripartite negative
      stranded RNA genome (consisting of the S, M, and L segments). Further spread of
      RVF into countries where the disease is not endemic may affect the economy and
      public health, and vaccination is an effective approach to prevent the spread of
      RVFV. A live-attenuated MP-12 vaccine is one of the best-characterized RVF
      vaccines for safety and efficacy and is currently conditionally licensed for use
      for veterinary purposes in the United States. Meanwhile, as of 2015, no other RVF
      vaccine has been conditionally or fully licensed for use in the United States.
      The MP-12 strain is derived from wild-type pathogenic strain ZH548, and its
      genome encodes 23 mutations in the three genome segments. However, the mechanism
      of MP-12 attenuation remains unknown. We characterized the attenuation of wild
      type pathogenic strain ZH501 carrying a mutation(s) of the MP-12 S, M, or L
      segment in a mouse model. Our results indicated that MP-12 is attenuated by the
      mutations in the S, M, and L segments, while the mutations in the M and L
      segments confer stronger attenuation than those in the S segment. We identified a
      combination of 3 amino acid changes, Y259H (Gn), R1182G (Gc), and R1029K (L),
      that was sufficient to attenuate ZH501. However, strain MP-12 with reversion
      mutations at those 3 sites was still highly attenuated. Our results indicate that
      MP-12 attenuation is supported by a combination of multiple partial attenuation
      mutations and a single reversion mutation is less likely to cause a reversion to
      virulence of the MP-12 vaccine. IMPORTANCE: Rift Valley fever (RVF) is a mosquito
      transmitted viral disease that is endemic to Africa and that has the potential to
      spread into other countries. Vaccination is considered an effective way to
      prevent the disease, and the only available veterinary RVF vaccine in the United
      States is a live-attenuated MP-12 vaccine, which is conditionally licensed.
      Strain MP-12 is different from its parental pathogenic RVFV strain, strain ZH548,
      because of the presence of 23 mutations. This study determined the role of
      individual mutations in the attenuation of the MP-12 strain. We found that full
      attenuation of MP-12 occurs by a combination of multiple mutations. Our findings
      indicate that a single reversion mutation will less likely cause a major
      reversion to virulence of the MP-12 vaccine.

PMID- 25948742
TI  - Human Memory B Cells Producing Potent Cross-Neutralizing Antibodies against Human
      Parechovirus: Implications for Prevalence, Treatment, and Diagnosis.
AB  - The family Picornaviridae is a large and diverse group of positive-sense RNA
      viruses, including human enteroviruses (EVs) and human parechoviruses (HPeVs).
      The human immune response against EVs and HPeVs is thought to be mainly humoral,
      and an insufficient neutralizing antibody (Ab) response during infection is a
      risk factor and can ultimately be life threatening. The accessibility of
      different antigenic sites and observed cross-reactivity make HPeVs a good target
      for development of therapeutic human monoclonal antibodies (MAbs). In this study,
      we generated two different human MAbs specific for HPeV by screening culture
      supernatants of Ab-producing human B cell cultures for direct neutralization of
      HPeV1. Both MAbs showed HPeV1-specific neutralization as well as neutralization
      of HPeV2. One antibody, AM18, cross-neutralized HPeV4, -5, and -6 and
      coxsackievirus A9 (CV-A9). VP1 capsid protein-specific assays confirmed that AM18
      bound VP1 of HPeV1, -2, and -4 with high affinity (11.5 pM). In contrast, the
      HPeV1-specific MAb AM28, which neutralized HPeV1 even more efficiently than did
      AM18, showed no cross-reactivity with HPeV3 to -6 or other EVs and did not bind
      any of the capsid proteins, suggesting that AM28 is specific for a conformation
      dependent, nonlinear epitope on the virus. The discovery of MAbs that are cross
      reactive between HPeVs may help development of HPeV treatment options with
      antibodies and vaccine design based on epitopes recognized by these antibodies.
      IMPORTANCE: HPeV infections are widespread among young children and adults,
      causing a broad range of disease. Infections can be severe and life threatening,
      while no antiviral treatment is available. Given that the absence of neutralizing
      Abs is a risk factor for severe disease in infants, treatment of picornavirus
      infections with MAbs would be a therapeutic option. To study antibody
      neutralization of HPeV in more detail, we generated two different HPeV1-specific
      human MAbs. Both MAbs show HPeV1-specific neutralization and cross-neutralized
      HPeV2. One MAb also cross-neutralized other HPeVs. Surprisingly, this MAb also
      neutralized CV-A9. These MAbs provide a unique tool for further research and for
      the diagnosis (antigen detection) and possible treatment of HPeV infections.

PMID- 25948743
TI  - Novel Functions of Hendra Virus G N-Glycans and Comparisons to Nipah Virus.
AB  - Hendra virus (HeV) and Nipah virus (NiV) are reportedly the most deadly pathogens
      within the Paramyxoviridae family. These two viruses bind the cellular entry
      receptors ephrin B2 and/or ephrin B3 via the viral attachment glycoprotein G, and
      the concerted efforts of G and the viral fusion glycoprotein F result in membrane
      fusion. Membrane fusion is essential for viral entry into host cells and for cell
      cell fusion, a hallmark of the disease pathobiology. HeV G is heavily N
      glycosylated, but the functions of the N-glycans remain unknown. We disrupted
      eight predicted N-glycosylation sites in HeV G by conservative mutations (Asn to
      Gln) and found that six out of eight sites were actually glycosylated (G2 to G7);
      one in the stalk (G2) and five in the globular head domain (G3 to G7). We then
      tested the roles of individual and combined HeV G N-glycan mutants and found
      functions in the modulation of shielding against neutralizing antibodies,
      intracellular transport, G-F interactions, cell-cell fusion, and viral entry.
      Between the highly conserved HeV and NiV G glycoproteins, similar trends in the
      effects of N-glycans on protein functions were observed, with differences in the
      levels at which some N-glycan mutants affected such functions. While the N-glycan
      in the stalk domain (G2) had roles that were highly conserved between HeV and NiV
      G, individual N-glycans in the head affected the levels of several protein
      functions differently. Our findings are discussed in the context of their
      contributions to our understanding of HeV and NiV pathogenesis and immune
      responses. IMPORTANCE: Viral envelope glycoproteins are important for viral
      pathogenicity and immune evasion. N-glycan shielding is one mechanism by which
      immune evasion can be achieved. In paramyxoviruses, viral attachment and membrane
      fusion are governed by the close interaction of the attachment proteins H/HN/G
      and the fusion protein F. In this study, we show that the attachment glycoprotein
      G of Hendra virus (HeV), a deadly paramyxovirus, is N-glycosylated at six sites
      (G2 to G7) and that most of these sites have important roles in viral entry, cell
      cell fusion, G-F interactions, G oligomerization, and immune evasion. Overall, we
      found that the N-glycan in the stalk domain (G2) had roles that were very
      conserved between HeV G and the closely related Nipah virus G, whereas individual
      N-glycans in the head quantitatively modulated several protein functions
      differently between the two viruses.

PMID- 25948744
TI  - Characterization of the Human Papillomavirus 16 E8 Promoter.
AB  - Persistent infections with certain human papillomaviruses (HPV) such as HPV16 are
      a necessary risk factor for the development of anogenital and oropharyngeal
      cancers. HPV16 genomes replicate as low-copy-number plasmids in the nucleus of
      undifferentiated keratinocytes, which requires the viral E1 and E2 replication
      proteins. The HPV16 E8^E2C (or E8^E2) protein limits genome replication by
      repressing both viral transcription and the E1/E2-dependent DNA replication. How
      E8^E2C expression is regulated is not understood. Previous transcript analyses
      indicated that the spliced E8^E2C RNA is initiated at a promoter located in the
      E1 region upstream of the E8 gene. Deletion and mutational analyses of the E8
      promoter region identify two conserved elements that are required for basal
      promoter activity in HPV-negative keratinocytes. In contrast, the transcriptional
      enhancer in the upstream regulatory region of HPV16 does not modulate basal E8
      promoter activity. Cotransfection studies indicate that E8^E2C inhibits, whereas
      E2 weakly activates, the E8 promoter. Interestingly, the cotransfection of E1 and
      E2 induces the E8 promoter much more strongly than the major early promoter, and
      this is partially dependent upon binding of E2 to Brd4. Mutation of E8 promoter
      elements in the context of HPV16 genomes results in an increased genome copy
      number and elevated levels of viral early and late transcripts. In summary, the
      promoter responsible for the expression of E8^E2C is both positively and
      negatively regulated by viral and cellular factors, and this regulatory circuit
      may be crucial to maintain a low but constant copy number of HPV16 genomes in
      undifferentiated cells. IMPORTANCE: HPV16 replicates in differentiating epithelia
      and can cause cancer. How HPV16 maintains its genome in undifferentiated cells at
      a low but constant level is not well understood but may be relevant for the
      immunological escape of HPV16 in the basal layers of the infected epithelium.
      This study demonstrates that the expression of the viral E8^E2C protein, which is
      a potent inhibitor of viral replication in undifferentiated cells, is driven by a
      separate promoter. The E8 promoter is both positively and negatively regulated by
      viral proteins and thus most likely acts as a sensor and modulator of viral copy
      number.

PMID- 25948745
TI  - Cross-Reactive Neuraminidase-Inhibiting Antibodies Elicited by Immunization with
      Recombinant Neuraminidase Proteins of H5N1 and Pandemic H1N1 Influenza A Viruses.
AB  - Neuraminidase (NA), an influenza virus envelope glycoprotein, removes sialic acid
      from receptors for virus release from infected cells. For this study, we used a
      baculovirus-insect cell expression system to construct and purify recombinant NA
      (rNA) proteins of H5N1 (A/Vietnam/1203/2004) and pandemic H1N1 (pH1N1)
      (A/Texas/05/2009) influenza viruses. BALB/c mice immunized with these proteins
      had high titers of NA-specific IgG and NA-inhibiting (NI) antibodies against
      H5N1, pH1N1, H3N2, and H7N9 viruses. H5N1 rNA immunization resulted in higher
      quantities of NA-specific antibody-secreting B cells against H5N1 and
      heterologous pH1N1 viruses in the spleen. H5N1 rNA and pH1N1 rNA immunizations
      both provided complete protection against homologous virus challenges, with H5N1
      rNA immunization providing better protection against pH1N1 virus challenges.
      Cross-reactive NI antibodies were further dissected via pH1N1 rNA protein
      immunizations with I149V (NA with a change of Ile to Val at position 149), N344Y,
      and I365T/S366N NA mutations. The I365T/S366N mutation of pH1N1 rNA enhanced
      cross-reactive NI antibodies against H5N1, H3N2, and H7N9 viruses. It is our hope
      that these findings provide useful information for the development of an NA-based
      universal influenza vaccine. IMPORTANCE: Neuraminidase (NA) is an influenza virus
      enzymatic protein that cleaves sialic acid linkages on infected cell surfaces,
      thus facilitating viral release and contributing to viral transmission and mucus
      infection. In currently available inactivated or live, attenuated influenza
      vaccines based on the antigenic content of hemagglutinin proteins, vaccine
      efficacy can be contributed partly through NA-elicited immune responses. We
      investigated the NA immunity of different recombinant NA (rNA) proteins
      associated with pH1N1 and H5N1 viruses. Our results indicate that H5N1 rNA
      immunization induced more potent cross-protective immunity than pH1N1 rNA
      immunization, and three mutated residues, I149V, I365T, and S366N, near the NA
      enzyme active site(s) are linked to enhanced cross-reactive NA-inhibiting
      antibodies against heterologous and heterosubtypic influenza A viruses. These
      findings provide useful information for the development of an NA-based universal
      influenza vaccine.

PMID- 25948746
TI  - Inclusion of Flagellin during Vaccination against Influenza Enhances Recall
      Responses in Nonhuman Primate Neonates.
AB  - Influenza virus can cause life-threatening infections in neonates and young
      infants. Although vaccination is a major countermeasure against influenza,
      current vaccines are not approved for use in infants less than 6 months of age,
      in part due to the weak immune response following vaccination. Thus, there is a
      strong need to develop new vaccines with improved efficacy for this vulnerable
      population. To address this issue, we established a neonatal African green monkey
      (AGM) nonhuman primate model that could be used to identify effective influenza
      vaccine approaches for use in young infants. We assessed the ability of
      flagellin, a Toll-like receptor 5 (TLR5) agonist, to serve as an effective
      adjuvant in this at-risk population. Four- to 6-day-old AGMs were primed and
      boosted with inactivated PR8 influenza virus (IPR8) adjuvanted with either wild
      type flagellin or inactive flagellin with a mutation at position 229 (m229), the
      latter of which is incapable of signaling through TLR5. Increased IgG responses
      were observed following a boost, as well as at early times after challenge, in
      infants vaccinated with flagellin-adjuvanted IPR8. Inclusion of flagellin during
      vaccination also resulted in a significantly increased number of influenza virus
      specific T cells following challenge compared to the number in infants vaccinated
      with the m229 adjuvant. Finally, following challenge infants vaccinated with IPR8
      plus flagellin exhibited a reduced pathology in the lungs compared to that in
      infants that received IPR8 plus m229. This study provides the first evidence of
      flagellin-mediated enhancement of vaccine responses in nonhuman primate neonates.
      IMPORTANCE: Young infants are particularly susceptible to severe disease as a
      result of influenza virus infection. Compounding this is the lack of effective
      vaccines for use in this vulnerable population. Here we describe a vaccine
      approach that results in improved immune responses and protection in young
      infants. Incorporation of flagellin during vaccination resulted in increased
      antibody and T cell responses together with reduced disease following virus
      infection. These results suggest that flagellin may serve as an effective
      adjuvant for vaccines targeted to this vulnerable population.

PMID- 25948748
TI  - Interferon Gamma Prolongs Survival of Varicella-Zoster Virus-Infected Human
      Neurons In Vitro.
AB  - Infection of human neurons in vitro with varicella-zoster virus (VZV) at a low
      multiplicity of infection does not result in a cytopathic effect (CPE) within 14
      days postinfection (dpi), despite production of infectious virus. We showed that
      by 28 dpi a CPE ultimately developed in infected neurons and that interferon
      gamma inhibited not only the CPE but also VZV DNA accumulation, transcription,
      and virus production, thereby prolonging the life of VZV-infected neurons. 

PMID- 25948747
TI  - Human Cytomegalovirus pUL47 Modulates Tegumentation and Capsid Accumulation at
      the Viral Assembly Complex.
AB  - Human cytomegalovirus (HCMV) tegument protein pUL47 is an interaction partner of
      pUL48 and highly conserved among herpesviruses. It is closely associated with the
      capsid and has an important function early in infection. Here, we report a
      specific role of pUL47 in the tegumentation of capsids in the cytoplasm. A newly
      generated mutant virus (TB-47stop), in which expression of pUL47 is blocked,
      exhibited a severe impairment in cell-to-cell spread and release of infectivity
      from infected cells. Ultrastructural analysis of TB-47stop-infected cells clearly
      showed cytoplasmic accumulations of nonenveloped capsids that were only partially
      tegumented, indicating that these capsids failed to complete tegumentation.
      Nevertheless, these accumulations were positive for HCMV inner tegument proteins
      pp150 and pUL48, suggesting that their attachment to capsids occurs independently
      of pUL47. Despite these morphological alterations, fully enveloped virus
      particles were found in the extracellular space and at the viral assembly complex
      (vAC) of TB-47stop-infected cells, indicating that pUL47 is not essential for the
      generation of virions. We confirmed findings that incorporation of pUL48 into
      virions is impaired in the absence of pUL47. Interestingly, pUL47 exhibited a
      strong nuclear localization in transfected cells, whereas it was found
      exclusively at the vAC in the context of virus infection. Colocalization of pUL47
      and pUL48 at the vAC is consistent with their interaction. We also found a shift
      to a more nuclear localization of pUL47 when the expression of pUL48 was reduced.
      Summarizing our results, we hypothesize that pUL48 directs pUL47 to the vAC to
      promote tegumentation and secondary envelopment of capsids. IMPORTANCE:
      Generation of infectious HCMV particles requires an organized and multistep
      process involving the action of several viral and cellular proteins as well as
      protein-protein interactions. A better understanding of these processes is
      important for understanding the biology of HCMV and may help to identify targets
      for antiviral intervention. Here, we identified tegument protein pUL47 to
      function in tegumentation and proper trafficking of capsids during late phases of
      infection. Although pUL47 is not essential for the generation and release of
      infectious virions, its absence led to massive accumulations of partially
      tegumented capsids at the cell periphery. Detection of pUL48 at these
      accumulations indicated a pUL47-independent attachment of pUL48 to the capsid. On
      the other hand, localization of pUL47 to the vAC during infection appeared to be
      dependent on tegument protein pUL48, which suggests an intricate interplay of
      these proteins for normal generation of infectious virus progeny.

PMID- 25948749
TI  - Roles of Phosphorylation of the Nucleocapsid Protein of Mumps Virus in Regulating
      Viral RNA Transcription and Replication.
AB  - Mumps virus (MuV) is a paramyxovirus with a negative-sense nonsegmented RNA
      genome. The viral RNA genome is encapsidated by the nucleocapsid protein (NP) to
      form the ribonucleoprotein (RNP), which serves as a template for transcription
      and replication. In this study, we investigated the roles of phosphorylation
      sites of NP in MuV RNA synthesis. Using radioactive labeling, we first
      demonstrated that NP was phosphorylated in MuV-infected cells. Using both liquid
      chromatography-mass spectrometry (LC-MS) and in silico modeling, we identified
      nine putative phosphorylated residues within NP. We mutated these nine residues
      to alanine. Mutation of the serine residue at position 439 to alanine (S439A) was
      found to reduce the phosphorylation of NP in transfected cells by over 90%. The
      effects of these mutations on the MuV minigenome system were examined. The S439A
      mutant was found to have higher activity, four mutants had lower activity, and
      four mutants had similar activity compared to wild-type NP. MuV containing the
      S439A mutation had 90% reduced phosphorylation of NP and enhanced viral RNA
      synthesis and viral protein expression at early time points after infection,
      indicating that S439 is the major phosphorylation site of NP and its
      phosphorylation plays an important role in downregulating viral RNA synthesis.
      IMPORTANCE: Mumps virus (MuV), a paramyxovirus, is an important human pathogen
      that is reemerging in human populations. Nucleocapsid protein (NP) of MuV is
      essential for viral RNA synthesis. We have identified the major phosphorylation
      site of NP. We have found that phosphorylation of NP plays a critical role in
      regulating viral RNA synthesis. The work will lead to a better understanding of
      viral RNA synthesis and possible novel targets for antiviral drug development.

PMID- 25948751
TI  - Ecological Drivers of Virus Evolution: Astrovirus as a Case Study.
AB  - Although RNA viruses exhibit a high frequency of host jumps, major differences
      exist among the different virus families. Astroviruses infect a wide range of
      hosts, affecting both public health systems and economic production chains. Here
      we delineate the ecological and adaptive processes that drive the cross-species
      transmission of astroviruses. We observe that distinct transmission zones
      determine the prevailing astrovirus host and virus diversity, which in turn
      suggests that no single host group (e.g., bats) can be the natural reservoir, as
      illustrated through our phylogenetic analysis. 

PMID- 25948750
TI  - LMP1-Induced Sumoylation Influences the Maintenance of Epstein-Barr Virus Latency
      through KAP1.
AB  - As a herpesvirus, Epstein-Barr virus (EBV) establishes a latent infection that
      can periodically undergo reactivation, resulting in lytic replication and the
      production of new infectious virus. Latent membrane protein-1 (LMP1), the
      principal viral oncoprotein, is a latency-associated protein implicated in
      regulating viral reactivation and the maintenance of latency. We recently found
      that LMP1 hijacks the SUMO-conjugating enzyme Ubc9 via its C-terminal activating
      region-3 (CTAR3) and induces the sumoylation of cellular proteins. Because
      protein sumoylation can promote transcriptional repression, we hypothesized that
      LMP1-induced protein sumoylation induces the repression of EBV lytic promoters
      and helps maintain the viral genome in its latent state. We now show that with
      inhibition of LMP1-induced protein sumoylation, the latent state becomes less
      stable or leakier in EBV-transformed lymphoblastoid cell lines. The cells are
      also more sensitive to viral reactivation induced by irradiation, which results
      in the increased production and release of infectious virus, as well as increased
      susceptibility to ganciclovir treatment. We have identified a target of LMP1
      mediated sumoylation that contributes to the maintenance of latency in this
      context: KRAB-associated protein-1 (KAP1). LMP1 CTAR3-mediated sumoylation
      regulates the function of KAP1. KAP1 also binds to EBV OriLyt and immediate early
      promoters in a CTAR3-dependent manner, and inhibition of sumoylation processes
      abrogates the binding of KAP1 to these promoters. These data provide an
      additional line of evidence that supports our findings that CTAR3 is a distinct
      functioning regulatory region of LMP1 and confirm that LMP1-induced sumoylation
      may help stabilize the maintenance of EBV latency. IMPORTANCE: Epstein-Barr virus
      (EBV) latent membrane protein-1 (LMP1) plays an important role in the maintenance
      of viral latency. Previously, we documented that LMP1 targets cellular proteins
      to be modified by a ubiquitin-like protein (SUMO). We have now identified a
      function for this LMP1-induced modification of cellular proteins in the
      maintenance of EBV latency. Because latently infected cells have to undergo viral
      reactivation in order to be vulnerable to antiviral drugs, these findings
      identify a new way to increase the rate of EBV reactivation, which increases cell
      susceptibility to antiviral therapies.

PMID- 25948752
TI  - Adaptive Mutations That Occurred during Circulation in Humans of H1N1 Influenza
      Virus in the 2009 Pandemic Enhance Virulence in Mice.
AB  - During the 2009 H1N1 influenza pandemic, infection attack rates were particularly
      high among young individuals who suffered from pneumonia with occasional death.
      Moreover, previously reported determinants of mammalian adaptation and
      pathogenicity were not present in 2009 pandemic H1N1 influenza A viruses. Thus,
      it was proposed that unknown viral factors might have contributed to disease
      severity in humans. In this study, we performed a comparative analysis of two
      clinical 2009 pandemic H1N1 strains that belong to the very early and later
      phases of the pandemic. We identified mutations in the viral hemagglutinin (HA)
      and the nucleoprotein (NP) that occurred during pandemic progression and mediate
      increased virulence in mice. Lethal disease outcome correlated with elevated
      viral replication in the alveolar epithelium, increased proinflammatory cytokine
      and chemokine responses, pneumonia, and lymphopenia in mice. These findings show
      that viral mutations that have occurred during pandemic circulation among humans
      are associated with severe disease in mice. IMPORTANCE: In this study, novel
      determinants of 2009 pandemic H1N1 influenza pathogenicity were identified in the
      viral hemagglutinin (HA) and the nucleoprotein (NP) genes. In contrast to highly
      pathogenic avian influenza viruses, increased virulence in mice did not correlate
      with enhanced polymerase activity but with reduced activity. Lethal 2009 pandemic
      H1N1 infection in mice correlated with lymphopenia and severe pneumonia. These
      studies suggest that molecular mechanisms that mediate 2009 pandemic H1N1
      influenza pathogenicity are distinct from those that mediate avian influenza
      virus pathogenicity in mice.

PMID- 25948754
TI  - Variation in Dube3a expression affects neurotransmission at the Drosophila
      neuromuscular junction.
AB  - Changes in UBE3A expression levels in neurons can cause neurogenetic disorders
      ranging from Angelman syndrome (AS) (decreased levels) to autism (increased
      levels). Here we investigated the effects on neuronal function of varying UBE3A
      levels using the Drosophila neuromuscular junction as a model for both of these
      neurogenetic disorders. Stimulations that evoked excitatory junction potentials
      (EJPs) at 1 Hz intermittently failed to evoke EJPs at 15 Hz in a significantly
      higher proportion of Dube3a over-expressors using the pan neuronal GAL4 driver
      C155-GAL4 (C155-GAL4>UAS-Dube3a) relative to controls (C155>+ alone). However, in
      the Dube3a over-expressing larval neurons with no failures, there was no
      difference in EJP amplitude at the beginning of the train, or the rate of
      decrease in EJP amplitude over the course of the train compared to controls. In
      the absence of tetrodotoxin (TTX), spontaneous EJPs were observed in
      significantly more C155-GAL4>UAS-Dube3a larva compared to controls. In the
      presence of TTX, spontaneous and evoked EJPs were completely blocked and mEJP
      amplitude and frequency did not differ among genotypes. These data suggest that
      over-expression of wild type Dube3a, but not a ubiquitination defective Dube3a
      C/A protein, compromises the ability of motor neuron axons to support closely
      spaced trains of action potentials, while at the same time increasing
      excitability. EJPs evoked at 15 Hz in the absence of Dube3a (Dube3a(15b)
      homozygous mutant larvae) decayed more rapidly over the course of 30 stimulations
      compared to w(1118) controls, and Dube3a(15b) larval muscles had significantly
      more negative resting membrane potentials (RMP). However, these results could not
      be recapitulated using RNAi knockdown of Dube3a in muscle or neurons alone,
      suggesting more global developmental defects contribute to this phenotype. These
      data suggest that reduced UBE3A expression levels may cause global changes that
      affect RMP and neurotransmitter release from motorneurons at the neuromuscular
      junction. Similar affects of under- and over-expression of UBE3A on membrane
      potential and synaptic transmission may underlie the synaptic plasticity defects
      observed in both AS and autism. 

PMID- 25948753
TI  - Regulation of lipid droplet dynamics in Saccharomyces cerevisiae depends on the
      Rab7-like Ypt7p, HOPS complex and V1-ATPase.
AB  - It has now been clearly shown that lipid droplets (LDs) play a dynamic role in
      the cell. This was reinforced by LD proteomics which suggest that a significant
      number of trafficking proteins are associated with this organelle. Using
      microscopy, we showed that LDs partly co-localize with the vacuole in S.
      cerevisiae. Immunoblot experiments confirmed the association of the vacuolar Rab
      GTPase Rab7-like Ypt7p with LDs. We observed an increase in fatty acid content
      and LD number in ypt7Delta mutant and also changes in LD morphology and intra LD
      fusions, revealing a direct role for Ypt7p in LD dynamics. Using co
      immunoprecipitation, we isolated potential Ypt7p partners including, Vma13p, the
      H subunit of the V1 part of the vacuolar (H+) ATPase (V-ATPase). Deletion of the
      VMA13 gene, as well as deletion of three other subunits of the V1 part of the V
      ATPase, also increased the cell fatty acid content and LD number. Mutants of the
      Homotypic fusion and vacuole protein sorting (HOPS) complex showed similar
      phenotypes. Here, we demonstrated that LD dynamics and membrane trafficking
      between the vacuole and LDs are regulated by the Rab7-like Ypt7p and are impaired
      when the HOPS complex and the V1 domain of the V-ATPase are defective. 

PMID- 25948755
TI  - Precursor cells from Atlantic salmon (Salmo salar) visceral fat holds the
      plasticity to differentiate into the osteogenic lineage.
AB  - In order to study the potential plasticity of Atlantic salmon (Salmo salar)
      precursor cells (aSPCs) from the adipogenic mesenchyme cell lineage to
      differentiate to the osteogenic lineage, aSPCs were isolated and cultivated under
      either osteogenic or adipogenic promoting conditions. The results strengthen the
      hypothesis that aSPCs most likely are predestined to the adipogenic lineage, but
      they also hold the flexibility to turn into other lineages given the right
      stimuli. This assumption is supported by the fact that the transcription factor
      ppargamma , important for regulation of adiopogenesis, was silent in aSPCs grown
      in osteogenic media, while runx2, important for osteogenic differentiation, was
      not expressed in aSPCs cultivated in adipogenic media. After 2 weeks in
      osteogenic promoting conditions the cells started to deposit extracellular matrix
      and after 4 weeks, the cells started mineralizing secreted matrix. Microarray
      analyses revealed large-scale transcriptome responses to osteogenic medium after
      2 days, changes remained stable at day 15 and decreased by magnitude at day 30.
      Induction was observed in many genes involved in osteogenic differentiation,
      growth factors, regulators of development, transporters and production of
      extracellular matrix. Transcriptome profile in differentiating adipocytes was
      markedly different from differentiating osteoblasts with far fewer genes changing
      activity. The number of regulated genes slowly increased at the mature stage,
      when adipocytes increased in size and accumulated lipids. This is the first
      report on in vitro differentiation of aSPCs from Atlantic salmon to mineralizing
      osteogenic cells. This cell model system provides a new valuable tool for
      studying osteoblastogenesis in fish. 

PMID- 25948756
TI  - Short germ insects utilize both the ancestral and derived mode of Polycomb group
      mediated epigenetic silencing of Hox genes.
AB  - In insect species that undergo long germ segmentation, such as Drosophila, all
      segments are specified simultaneously at the early blastoderm stage. As
      embryogenesis progresses, the expression boundaries of Hox genes are established
      by repression of gap genes, which is subsequently replaced by Polycomb group
      (PcG) silencing. At present, however, it is not known whether patterning occurs
      this way in a more ancestral (short germ) mode of embryogenesis, where segments
      are added gradually during posterior elongation. In this study, two members of
      the PcG family, Enhancer of zeste (E(z)) and Suppressor of zeste 12 (Su(z)12),
      were analyzed in the short germ cricket, Gryllus bimaculatus. Results suggest
      that although stepwise negative regulation by gap and PcG genes is present in
      anterior members of the Hox cluster, it does not account for regulation of two
      posterior Hox genes, abdominal-A (abd-A) and Abdominal-B (Abd-B). Instead, abd-A
      and Abd-B are predominantly regulated by PcG genes, which is the mode present in
      vertebrates. These findings suggest that an intriguing transition of the PcG
      mediated silencing of Hox genes may have occurred during animal evolution. The
      ancestral bilaterian state may have resembled the current vertebrate mode of
      regulation, where PcG-mediated silencing of Hox genes occurs before their
      expression is initiated and is responsible for the establishment of individual
      expression domains. Then, during insect evolution, the repression by
      transcription factors may have been acquired in anterior Hox genes of short germ
      insects, while PcG silencing was maintained in posterior Hox genes. 

PMID- 25948758
TI  - Whose decision? Whose practice?

PMID- 25948757
TI  - Preserved Proteins from Extinct Bison latifrons Identified by Tandem Mass
      Spectrometry; Hydroxylysine Glycosides are a Common Feature of Ancient Collagen.
AB  - Bone samples from several vertebrates were collected from the Ziegler Reservoir
      fossil site, in Snowmass Village, Colorado, and processed for proteomics
      analysis. The specimens come from Pleistocene megafauna Bison latifrons, dating
      back ~ 120,000 years. Proteomics analysis using a simplified sample preparation
      procedure and tandem mass spectrometry (MS/MS) was applied to obtain protein
      identifications. Several bioinformatics resources were used to obtain peptide
      identifications based on sequence homology to extant species with annotated
      genomes. With the exception of soil sample controls, all samples resulted in
      confident peptide identifications that mapped to type I collagen. In addition, we
      analyzed a specimen from the extinct B. latifrons that yielded peptide
      identifications mapping to over 33 bovine proteins. Our analysis resulted in
      extensive fibrillar collagen sequence coverage, including the identification of
      posttranslational modifications. Hydroxylysine glucosylgalactosylation, a
      modification thought to be involved in collagen fiber formation and bone
      mineralization, was identified for the first time in an ancient protein dataset.
      Meta-analysis of data from other studies indicates that this modification may be
      common in well-preserved prehistoric samples. Additional peptide sequences from
      extracellular matrix (ECM) and non-ECM proteins have also been identified for the
      first time in ancient tissue samples. These data provide a framework for
      analyzing ancient protein signatures in well-preserved fossil specimens, while
      also contributing novel insights into the molecular basis of organic matter
      preservation. As such, this analysis has unearthed common posttranslational
      modifications of collagen that may assist in its preservation over time. The data
      are available via ProteomeXchange with identifier PXD001827.

PMID- 25948760
TI  - From basic to clinical practice in internal medicine.

PMID- 25948759
TI  - Misconstrual of EAPC's position paper on euthanasia.
AB  - This is a response to Barutta and Vollmann's article 'Physician-assisted death
      with limited access to palliative care.' I show how they misconstrue a key
      empirical statement made by the European Association for Palliative Care
      regarding legalisation of euthanasia and physician-assisted suicide.
      Additionally, I include some further remarks on the relationship between
      euthanasia and palliative care. I read with interest the article, which delineate
      well several positions and gives a nice overview of arguments presented on either
      side. I also found the line of argument unprejudiced and clear, and am sure
      people working within palliative care would benefit from reading it. 

PMID- 25948761
TI  - On-admission High Neutrophil to Lymphocyte Ratio as Predictor of In-hospital
      Adverse Cardiac Event in ST-elevation Myocardial Infarction.
AB  - AIM: to investigate the role of neutrophil-to-lymphocyte ratio (NLratio) in
      predicting in-hospital adverse cardiac events in patients with STEMI. METHODS:
      this was a cohort study on patients with STEMI onset 24 hour hospitalised in
      ICCU. NLratio was calculated as absolute neutrophil count divided with lymphocyte
      count measured by automated blood cell counter on admission.The outcome was in
      hospital adverse cardiac events, which were recorded during follow-up. The cut
      off value of NLratio to predict outcome was determined by ROC curve analysis.
      Univariate and multivariable analysis to assess whether high NLratio was
      independent predictor for in-hospital adverse events were performed. RESULTS:
      among 165 subjects, in-hospital adverse cardiac events occurred in 49 subjects
      (29%). The cut-off value of NLratio was 6.2. The univariate analysis showed that
      NLratio >6.2 had an odd ratio of 3.19 (95% CI 1.55-6.55, p=0.002) to develop in
      hospital adverse cardiac events. The multivariate analysis showed that NLratio
      was an independent predictor of in-hospital adverse cardiac events with an odd
      ratio of 4.10 (95% CI 1.59-10.54, p=0.003). CONCLUSION: high on-admission NLratio
      is an independent predictor for in-hospital adverse cardiac events in patients
      hospitalised for STEMI.

PMID- 25948762
TI  - Angiogenesis, inflammation, platelets count, and metastatic status as a predictor
      for thrombosis risk in nasopharyngeal carcinoma patients.
AB  - AIM: to assess the use of of angiogenesis, inflammation, platelets count, and
      metastatic status as predictors for thrombosis risk represented by soluble P
      selectin level in nasopharyngeal carcinoma (NPC) patients. METHODS: a cross
      sectional study was conducted on NPC patients at the Hematology and Oncology
      Clinic of Cipto Mangunkusumo Hospital, Jakarta, during Mei to October 2012. Data
      regarding angiogenesis (CD105 and VEGFR-2), inflammation (IL-6), platelets count,
      and metastatic status were assessed at enrollment, as well as soluble P-selectin
      levels in all eligible patients. Bivariate analysis continued with multiple
      linear regression analysis were done to identify independent predictors for
      soluble P-selectin levels. RESULTS: sixty NPC patients were enrolled in the
      study. There was correlation between platelet counts (r=0.389; p=0.002), IL-6
      (r=0.595; p<0.001) and number of metastatic sites (r=0.542; p<0.001) with soluble
      P-selectin level, and a linear regression analysis showed that these three
      variables can predict soluble P-selectin levels with adjusted R-square 65%. There
      was no correlation between VEGFR-2 and CD105 levels with soluble P-selectin
      levels. CONCLUSION: platelet counts, IL-6 level, and number of sites of
      metastasis can be used as predictors of soluble P-selectin level as parameter of
      thrombosis risk in NPC patients.

PMID- 25948763
TI  - Combination of Aspartate Aminotranferase and Tumor Necrosis Factor-alpha as Non
      Invasive Diagnostic Tools for Non Alcoholic Steatohepatitis (NASH).
AB  - AIM: to develop a non-invasive diagnostic test for non-alcoholic steatohepatitis
      NASH. METHODS: this is a cross-sectional study on non-alcoholic fatty liver
      disease (NAFLD) subjects. Sample was taken by consecutive sampling method.
      Diagnostic criteria of NAFLD were confirmed by liver biopsy. Clinical variables
      include metabolic syndrome, aspartate aminotransferase (AST), alanine
      aminotransferase (ALT), adiponectine, TNF-, insulin, homeostatic model assessment
      insulin resistance (HOMA-IR) index and liver biopsy. Patients were divided into
      two groups based on their liver biopsy, group 1: Non-NASH (NAFLD activity score
      <3) and group 2: NASH (NAFLD activity score of >4). Statistical analyses were
      performed using Student's t-test, Mann Whitney U, chi-square, the ROC curve,
      sensitivity and specificity test. RESULTS: fifty NAFLD patients were recruited,
      30 males and 20 females. Among these patients, 12 (24%) had type 2 diabetes, 36
      (72%) had metabolic syndrome, the remaining 2 (4%) did not fulfilled metabolic
      syndrome. Liver biopsy confirmed 21 (42%) non- NASH and 29 (58%) NASH
      respectively. Level of AST and ALT, plasma level of adiponectine and TNF- were
      statistically different between two groups. The AST level (>25 U/L) in
      combination with TNF- (>3.28 pg/cc) demonstrated a good diagnostic accuracy for
      NASH (Accuracy 82%, Sensitivity 76%, Specificity 90%, PPV 92%, and NPV 73%).
      CONCLUSION: the combined diagnostic tests of AST and TNF- plasma levels
      demonstrated a good accuracy for the detection of NASH among NAFLD patients. This
      combination test can be used as a noninvasive method to diagnose NASH.

PMID- 25948764
TI  - Effects of duration of breastfeeding during infancy on vascular dysfunction in
      adolescents.
AB  - AIM: to investigate the effect of breastfeeding duration on vascular
      characteristics in adolescence. METHODS: we conducted a retrospective cohort
      study on adolescents aged 15-18 years old. Breastfeeding duration was inquired
      using a questionnaire filled by parents and categorized into 0-<2, 2-<4, 4-<6, 6
      <12, and >12 months. Outcomes assessed were flow mediated dilation (FMD), carotid
      intima media thickness (CIMT), anthropometrics. Analysis was done using linear
      regression and MANOVA general linear model with cardiovascular risk factors as
      the dependent variables and breastfeeding duration as the independent variable
      with further adjustment for confounders. RESULTS: 285 subjects aged 15-18 years
      were enrolled. Breastfeeding duration of 4-<6 months was associated with thinner
      CIMT and the effect was more prominent after adjustment for gender and postnatal
      tobacco exposure (mean difference=24.28 micrometer, p=0.045). No statistically
      significant association was found with FMD. CONCLUSION: breastfeeding duration of
      4-<6 months is associated with thinner IMT and thus has a protective effect on
      the development of cardiovascular disease. However the association with FMD in
      adolescence is less clear.

PMID- 25948765
TI  - Prothrombotic Effect of Anti-beta-2 Glycoprotein-1 Antibodies on the Expression
      of Tissue Factor, Thrombomodulin, and Plasminogen Activator Inhibitor-1 in
      Endothelial Cells.
AB  - AIM: to analyse the effects of immunoglobulin(Ig)G and IgM anti-beta-2
      glycoprotein-1 (anti-2GP1) on the expression of tissue factor (TF),
      thrombomodulin (TM), and plasminogen activator inhibitor-1(PAI-1) of endothelial
      cells in the messenger RNA level. METHODS: laboratory experimental study in human
      umbilical vein endothelial cells (HUVEC) was done at Cipto Mangunkusumo
      Hospital/Faculty of Medicine, Universitas Indonesia. Samples are purified IgG
      anti-2GP1 from six antiphospholipid syndrome (APS) patients serum and IgM anti
      2GP1 from six APS patients serum. For controls, purified IgG from six normal
      human serum (IgM-NHS) and purified IgM from six normal human serum (IgM-NHS) were
      used. HUVEC were treated with purified IgG anti-2GP1, IgM anti-2GP1, IgG-NHS, IgM
      NHS for four hours of incubation. We measured TF, TM, and PAI-1 of HUVEC in mRNA
      relative expression levels (before and after treatment) by real time reverse
      transcription polymerase chain reaction. RESULTS: the mean value of TF, TM, and
      PAI-1 mRNA levels in HUVEC after treated with IgG anti-2GP1 compared to Ig-NHS
      were 3.14 (0.93)-, 0.31 (0.13)-, 5.33 (2.75)-fold respectively. In other hand,
      after treated with IgM anti-2GP1 compared to IgM-NHS, mRNA levels of TF, TM, and
      PAI-1 were 4.33 (1.98)-, 0.33 (0.22)-, 5.47 (2.64)-fold respectively. Before and
      after treatment with IgG anti-2GP1 showed significant differences of TF mRNA
      levels {1.09 (0.76) versus 3.14 (0.93), p=0.003}, TM mRNA levels {0.91 (0.11)
      versus 0.31(0.13), p=0.001}, and PAI-1 mRNA levels 0.93 (0.13) versus 5.33
      (2.75), p=0.013}. Before and after treatment with IgM anti-2GP1 showed
      significant differences of TF mRNA levels {1.03 (0.11) versus 4.33 (1.98),
      p=0.008}, TM mRNA levels {0.93 (0.08) versus 0.33 (0.22, p=0.003}, and PAI-1 mRNA
      levels {1.02 (0.10) versus 5.47 (2.64), p=0.01}. CONCLUSION: IgG anti-2GP1 and
      IgM anti-2GP1 increased TF and PAI-1 mRNA levels. However, IgG anti-2GP1 and IgM
      anti-2GP1 decreased TM mRNA levels. It proved that the mechanism of thrombosis in
      APS occurs through coagulation activation, reduction of fibrinolysis activity,
      and reduction of anticoagulant activity.

PMID- 25948766
TI  - A Validation Study for POSSUM and EuroSCORE as a Predictor of Mortality After
      Selective Cardiac Surgery.
AB  - AIM: to assess physiological and operative severity score for the enumeration of
      mortality (POSSUM) scoring system and compare it with European system for cardiac
      operative risk evaluation (EuroSCORE) scores in patients who underwent cardiac
      surgery from two hospitals in the southwestern region of Iran. METHODS: in this
      retrospective study, total of all 1420 patients who were admitted for elective
      cardiac surgery at our centers, from 2007 to 2012, were scored using the POSSUM
      and EuroSCORE systems. RESULTS: the overall mortality rate was 0.87%. Among the
      risk factors, history of diabetes, smoking, respiratory disease, and myocardial
      infarction, were significantly affect the mortality rate. Therefore, of these
      risk factors, only the hemoglobin was significantly correlated with the morbidity
      rate. The predictive accuracy of mortality equations was 74.5%. The lower
      predictive accuracy of mortality equations was 67.8% was observed using
      EuroSCORE. CONCLUSION: although results are statistically significant, but the
      analysis have never intended to affect the decision to operate, and this decision
      must be based on clinical expertise, because of the need to standardize data
      collection and stratify the risks involved in operations, scoring systems such as
      POSSUM should be used prospectively. However, if analyzed correctly, POSSUM is a
      good predictor of mortality in patients undergoing cardiac surgery.

PMID- 25948767
TI  - The Effect of High Poly Unsaturated Fatty Acid (PUFA) Dietary Supplementation on
      Inflammatory Status of Patients with Advanced Cervical Cancer on Radiation
      Treatment.
AB  - AIM: to identify the effect of high-PUFA dietary supplementation on inflammatory
      status of patients with advanced cervical cancer. METHODS: a randomized double
      blind clinical trial was conducted in patients with advanced cervical cancer who
      had undergone external radiation therapy at Department of Radiotherapy, Cipto
      Mangunkusumo Hospital, Jakarta, between April 2013 and April 2014. The
      inflammatory status was evaluated based on serum prostaglandin E2 (PGE2) levels
      using ELISA method. The dietary supplementation was isocaloric, isoprotein and
      contained PUFA with a ratio of -6: -3 fatty acid = 1.27:1 and supplementation
      without PUFA. Data were analyzed with statistical tests, including Shapiro-Wilk
      test, independent T-test and Mann-Whitney test. RESULTS: there was statistically
      no significant difference on PGE2 level between treatment and control groups
      (p=0.127). However, there was clinically significant difference, in which the
      treatment group had reduced PGE2 level by 8.9%; while the control group had
      increased level by 28.1%. CONCLUSION: dietary supplementation enriched with PUFA
      can reduce inflammatory status in patients with advanced cervical cancer. Reduced
      PGE2 level will lower the survival of cancer cells; therefore dietary
      supplementation enriched with PUFA with a ratio of -6 : -3 fatty acid = 1.27 : 1
      along with radiation therapy may improve tumor response to radiation.

PMID- 25948768
TI  - MRSA infection in patients hospitalized at Sanglah Hospital: a case series.
AB  - This is the first report of MRSA infection in Sanglah Hospital. We reviewed eight
      patients with MRSA infection from microbiologi laboratory records between January
      and May 2011, than followed by tracing medical records to obtained data of the
      patients. Five of cases with sepsis, 1 case with osteomyelitis, and the two
      others with mediastinitis and pneumonia. The patients were kept in private
      isolated room and barrier-nursing technique was strictly followed. Further action
      was culturing specimen taken from the patients nose, throat, axilla, and samples
      taken from the health care workers, with no MRSA colonization were found. Five
      patients demonstrated good respond to intravenous administration of either
      vancomycin or linezolide. Three were died due to septic shock before the
      laboratory culture and antimicrobial susceptibility availabled. All of the
      strains isolated more than 48 hours after admission and also demonstrated
      clinical risk factors for hospitalized acquired MRSA (HA-MRSA). These strains had
      resistance to b-lactams but remain susceptible to many non b-lactam antibiotics,
      as reported in some community acquired MRSA (CA-MRSA) isolates. Future study
      using molecular typing required to fully understand the magnitude and ongoing
      evolution of MRSA infections.

PMID- 25948769
TI  - Hemoperitoneum caused by spontaneous rupture of hepatocellular carcinoma.
AB  - We are reporting a male, 46 years old came to emergency unit with a chief
      complaint of abdominal tenderness since 1 day prior to admission. No history of
      abdominal trauma. He often felt abdominal discomfort for the last 5 years.
      Physical examination revealed decreased consciousness, shock, pale conjungtiva,
      distended abdomen, with tenderness of the whole abdomen on palpation, and no
      bowel movement. Laboratory examination found anemia, leucocytosis, normal amilase
      and lipase. FAST (focus assissted Sonography on trauma) found massive ascites.
      Patient underwent cito laparotomic exploration that found blood on abdominal
      cavity, nodular liver, and actively bleeding tumour of liver. During
      hospitalization, patient recovered and discharged. In the case of acute abdomen,
      spontaneous ruptured hepatocellular carcinoma (HCC) is one of differential
      diagnosis, considering high incidence of HCC in South East Asia, especially
      Indonesia. Confirming diagnosis of generalized peritonitis requires abdominal CT
      scan and ultrasonography, to rule out ruptured HCC. 

PMID- 25948770
TI  - Dendritic cells in Graves' disease.
AB  - Dendritic cells are major antigen-presenting cells (APC) that stimulate naive T
      cells, which induce adaptive immune responses. Graves' disease (GD) is an
      autoimmune disease characterized by the presence of autoantibodies against
      Thyroid Stimulating Hormone Receptor (TSHR). The autoantibodies bind with TSHR
      and stimulate thyroid hormone production. Dendritic cells are still the major APC
      in GD immune response although thyrocytes in GD can also express Major
      Histocompatibility Class (MHC) class II molecule. Studies about DC in GD have
      been conducted by isolating intra-thyroid DC or DC in peripheral circulation.
      Results of DC studies in GD are still controversial. Changes in number and
      profile of DC are found, which indicate altered immune response activity and
      defects of regulator T cell (Treg) in GD. 

PMID- 25948771
TI  - Major Aorto Pulmonary Collateral Arteries (MAPCA) with Tetralogy of Fallot and
      Pulmonary Artesia in Middle Age Adult: a Rare Finding.

PMID- 25948772
TI  - Relationship Between Salted Fish Consumption and Nasopharyngeal Carcinoma: An
      Evidence-based Case Report.
AB  - AIM: to know the relationship between salted fish consumption and nasopharyngeal
      carcinoma (NPC). METHODS: we searched for the articles from PubMed(r) and
      ScienceDirect(r) based on our clinical question. After filtered with our in- and
      exclusion criteria, we had six articles about this topic, all of them were case
      control studies. All articles were then critically appraised for their validity,
      importance, and applicability. RESULTS: there was no consistent relationship
      between salted fish consumption and NPC. Worth to note that those studies wo
      showed the firm relationship were conducted in Southern China, where the
      incidence of NPC was extremely high and related to specific Chineese-style salted
      fish consumption. CONCLUSION: there was an inconsistent relationship between
      salted fish consumption and NPC.

PMID- 25948773
TI  - Management of hypertension in pregnancy.
AB  - Hypertension-related maternal mortality reaches 16% when it is compared to other
      causes of maternal mortality such as sepsis, bleeding or abortus. Pregnant women
      with hypertension disorder are at increased risk for experiencing numerous
      complications including disseminated intravascular coagulation (DIC), cerebral
      hemorrhage, liver dysfunction and acute renal failure; while to the fetus, it may
      cause intrauterine growth retardation, prematurity and perinatal mortality.
      Hypertension in pregnancy should be managed appropriately to reduce maternal and
      fetal morbidity and mortality rate, i.e. by preventing women from getting the
      risks of increased blood pressure, preventing disease progression and preventing
      the development of seizure and considering termination of pregnancy in life
      threatening situation for maternal and fetal health. 

PMID- 25948774
TI  - Sunitinib but not VEGF blockade inhibits cancer stem cell endothelial
      differentiation.
AB  - Different mechanisms of angiogenesis and vasculogenesis are involved in the
      development of the tumor vasculature. Among them, cancer stem cells are known to
      contribute to tumor vasculogenesis through their direct endothelial
      differentiation. Here, we investigated the effect of anti-angiogenic therapy on
      vasculogenesis of cancer stem cells derived from breast and renal carcinomas. We
      found that all the anti-angiogenic approaches impaired proliferation and survival
      of cancer stem cells once differentiated into endothelial cells in vitro and
      reduced murine angiogenesis in vivo. At variance, only VEGF-receptor inhibition
      using the non-specific tyrosine kinase inhibitor Sunitinib or the anti-VEGF
      receptor 2 neutralizing antibody, but not VEGF blockade using Bevacizumab,
      impaired the process of endothelial differentiation in vitro, suggesting a VEGF
      independent mechanism. In addition, tyrosine kinase inhibition by Sunitinib but
      not VEGF blockade using the soluble VEGF trap sFlk1 inhibited the cancer stem
      cell-induced vasculogenesis in vivo. Accordingly, Sunitinib but not Bevacizumab
      inhibited the induction of hypoxia-inducible factor pathway occurring during
      endothelial differentiation under hypoxia. The present results highlight a
      differential effect of VEGF-receptor blockade versus VEGF inhibition in tumor
      vascularization. VEGFR blockade inhibits the process of tumor vasculogenesis
      occurring during tumor hypoxia whereas the effect of VEGF inhibition appears
      restricted to differentiated endothelial cells. 

PMID- 25948775
TI  - Consequences of combining siRNA-mediated DNA methyltransferase 1 depletion with 5
      aza-2'-deoxycytidine in human leukemic KG1 cells.
AB  - 5-azacytidine and 5-aza-2'-deoxycytidine are clinically used to treat patients
      with blood neoplasia. Their antileukemic property is mediated by the trapping and
      the subsequent degradation of a family of proteins, the DNA methyltransferases
      (DNMT1, DNMT3A, and DNMT3B) leading to DNA demethylation, tumor suppressor gene
      re-expression and DNA damage. Here we studied the respective role of each DNMT in
      the human leukemia KG1 cell line using a RNA interference approach. In addition
      we addressed the role of DNA damage formation in DNA demethylation by 5-aza-2'
      deoxycytidine. Our data show that DNMT1 is the main DNMT involved in DNA
      methylation maintenance in KG1 cells and in mediating DNA damage formation upon
      exposure to 5-aza-2'-deoxycytidine. Moreover, KG1 cells express the DNMT1 protein
      at a level above the one required to ensure DNA methylation maintenance, and we
      identified a threshold for DNMT1 depletion that needs to be exceeded to achieve
      DNA demethylation. Most interestingly, by combining DNMT1 siRNA and treatment
      with low dose of 5-aza-2'-deoxycytidine, it is possible to uncouple DNA damage
      formation from DNA demethylation. This work strongly suggests that a direct
      pharmacological inhibition of DNMT1, unlike the use of 5-aza-2'-deoxycytidine,
      should lead to tumor suppressor gene hypomethylation and re-expression without
      inducing major DNA damage in leukemia. 

PMID- 25948776
TI  - PKM2 promotes glucose metabolism and cell growth in gliomas through a mechanism
      involving a let-7a/c-Myc/hnRNPA1 feedback loop.
AB  - Tumor cells metabolize more glucose to lactate in aerobic or hypoxic conditions
      than non-tumor cells. Pyruvate kinase isoenzyme type M2 (PKM2) is crucial for
      tumor cell aerobic glycolysis. We established a role for let-7a/c
      Myc/hnRNPA1/PKM2 signaling in glioma cell glucose metabolism. PKM2 depletion via
      siRNA inhibits cell proliferation and aerobic glycolysis in glioma cells. C-Myc
      promotes up-regulation of hnRNPA1 expression, hnRNPA1 binding to PKM pre-mRNA,
      and the subsequent formation of PKM2. This pathway is downregulated by the
      microRNA let-7a, which functionally targets c-Myc, whereas hnRNPA1 blocks the
      biogenesis of let-7a to counteract its ability to downregulate the c
      Myc/hnRNPA1/PKM2 signaling pathway. The down-regulation of c-Myc/ hnRNPA1/PKM2 by
      let-7a is verified using a glioma xenograft model. These results suggest that let
      7a, c-Myc and hnRNPA1 from a feedback loop, thereby regulating PKM2 expression to
      modulate glucose metabolism of glioma cells. These findings elucidate a new
      pathway mediating aerobic glycolysis in gliomas and provide an attractive
      potential target for therapeutic intervention. 

PMID- 25948777
TI  - PI3K/AKT/mTOR pathway plays a major pathogenetic role in glycogen accumulation
      and tumor development in renal distal tubules of rats and men.
AB  - Activation of the PI3K/AKT/mTOR pathway is a crucial molecular event in human
      clear cell renal cell carcinoma (ccRCC), and is also upregulated in diabetic
      nephropathy. In diabetic rats metabolic changes affect the renal distal tubular
      epithelium and lead to glycogen-storing Armanni-Ebstein lesions (AEL), precursor
      lesions of RCC in the diabetes induced nephrocarcinogenesis model. These lesions
      resemble human sporadic clear cell tubules (CCT) and tumor cells of human
      ccRCC.Human sporadic CCT were examined in a collection of 324 nephrectomy
      specimen, in terms of morphologic, metabolic and molecular alterations, and
      compared to preneoplastic CCT and RCC developed in the rat following
      streptozotocin-induced diabetes or N-Nitrosomorpholine administration. Diabetic
      and non-diabetic rats were subjected to the dual PI3K/mTOR inhibitor,
      NVP/BEZ235.Human sporadic CCT could be detected in 17.3% of kidney specimens.
      Human and rat renal CCT display a strong induction of the PI3K/AKT/mTOR pathway
      and related metabolic alterations. Proteins involved in glycolysis and de novo
      lipogenesis were upregulated. In in vivo experiments, dual inhibition of PI3K and
      mTOR resulted in a reduction of proliferation of rat diabetes related CCT and
      increased autophagic activity.The present data indicate that human sporadic CCT
      exhibit a pattern of morphologic and metabolic alterations similar to
      preneoplastic lesions in the rat model. Activation of the PI3K/AKT/mTOR pathway
      in glycogenotic tubuli is a remarkable molecular event and suggests a
      preneoplastic character of these lesions also in humans. 

PMID- 25948778
TI  - Impact of aging on calcium influx and potassium channel characteristics of T
      lymphocytes.
AB  - Adaptive immunity and T cell function are affected by aging. Calcium influx
      patterns, regulated by Kv1.3 and IKCa1 potassium channels, influence T cell
      activation. We aimed to compare calcium influx kinetics in CD8, Th1 and Th2 cells
      in human peripheral blood samples obtained from five different age groups (cord
      blood, 10-15 ys, 25-40 ys, 45-55 ys, 60-75 ys).We measured calcium influx using
      flow cytometry in samples treated with or without specific inhibitors of Kv1.3
      and IKCa1 channels (MGTX and TRAM, respectively).Calcium influx was higher in Th1
      cells of adults, however, its extent decreased again with aging. Importantly,
      these changes were not detected in Th2 cells, where the pattern of calcium influx
      kinetics is similar throughout all investigated age groups. MGTX had a more
      pronounced inhibitory effect on calcium influx in Th2 cells, while in Th1 cells
      the same was true for TRAM in the 25-40 ys and 45-55 ys groups. Calcium influx of
      CD8 cells were inhibited to a similar extent by both applied inhibitors in these
      groups, and had no effect in the elderly.Altered lymphocyte potassium channel
      inhibitory patterns, regulators of calcium influx kinetics, might contribute to
      the development of age-related changes of T cell function. 

PMID- 25948780
TI  - Bacillus coagulans GBI-30, 6086 Modulates Faecalibacterium prausnitzii in Older
      Men and Women.
AB  - BACKGROUND: Advancing age is linked to a decrease in beneficial bacteria such as
      Bifidobacterium spp. and reduced aspects of innate immune function. OBJECTIVES:
      We investigated whether daily consumption of a probiotic [Bacillus coagulans GBI
      30, 6086 (BC30); GanedenBC(30)] could improve immune function and gut function in
      men and women aged 65-80 y, using a double-blind, placebo-controlled crossover
      design. METHOD: Thirty-six volunteers were recruited and randomly assigned to
      receive either a placebo (microcrystalline cellulose) or the probiotic BC30 (1 *
      10(9) colony-forming units/capsule). Volunteers consumed 1 treatment capsule per
      day for 28 d, followed by a 21-d washout period before switching to the other
      treatment. Blood and fecal samples were collected at the beginning and end of
      each treatment period. Fecal samples were used to enumerate bacterial groups and
      concentrations of calprotectin. Peripheral blood mononuclear cells (PBMCs) were
      extracted from whole blood to assess natural killer cell activity and
      lipopolysaccharide (LPS)-stimulated cytokine production. C-reactive protein
      concentrations were measured in plasma. RESULTS: Consumption of BC30
      significantly increased populations of Faecalibacterium prausnitzii by 0.1 log10
      cells/mL more than during consumption of the placebo (P = 0.03), whereas
      populations of Bacillus spp. increased significantly by 0.5 log10 cells/mL from
      baseline in volunteers who consumed BC30 (P = 0.007). LPS-stimulated PBMCs showed
      a 0.2 ng/mL increase in the anti-inflammatory cytokine IL-10 28 d after
      consumption of BC30 (P < 0.05), whereas the placebo did not affect IL-10, and no
      overall difference was found in the effect of the treatments. CONCLUSIONS: Daily
      consumption of BC30 by adults aged 65-80 y can increase beneficial groups of
      bacteria in the human gut and potentially increase production of anti
      inflammatory cytokines. This study shows the potential benefits of a probiotic to
      improve dysbiosis via modulation of the microbiota in older persons.

PMID- 25948779
TI  - Inflammatory and oncogenic roles of a tumor stem cell marker doublecortin-like
      kinase (DCLK1) in virus-induced chronic liver diseases.
AB  - Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related
      mortality worldwide. We previously showed that a tumor/cancer stem cell (CSC)
      marker, doublecortin-like kinase (DCLK1) positively regulates hepatitis C virus
      (HCV) replication, and promotes tumor growth in colon and pancreas. Here, we
      employed transcriptome analysis, RNA interference, tumor xenografts, patient's
      liver tissues and hepatospheroids to investigate DCLK1-regulated inflammation and
      tumorigenesis in the liver. Our studies unveiled novel DCLK1-controlled feed
      forward signaling cascades involving calprotectin subunit S100A9 and NFkappaB
      activation as a driver of inflammation. Validation of transcriptome data suggests
      that DCLK1 co-expression with HCV induces BRM/SMARCA2 of SW1/SNF1 chromatin
      remodeling complexes. Frequently observed lymphoid aggregates including hepatic
      epithelial and stromal cells of internodular septa extensively express DCLK1 and
      S100A9. The DCLK1 overexpression also correlates with increased levels of S100A9,
      c-Myc, and BRM levels in HCV/HBV-positive patients with cirrhosis and HCC. DCLK1
      silencing inhibits S100A9 expression and hepatoma cell migration. Normal human
      hepatocytes (NHH)-derived spheroids exhibit CSC properties. These results provide
      new insights into the molecular mechanism of the hepatitis B/C-virus induced
      liver inflammation and tumorigenesis via DCLK1-controlled networks. Thus, DCLK1
      appears to be a novel therapeutic target for the treatment of inflammatory
      diseases and HCC. 

PMID- 25948781
TI  - Environmental, Dietary, and Behavioral Factors Distinguish Chinese Adults with
      High Waist-to-Height Ratio with and without Inflammation.
AB  - BACKGROUND: The environmental and behavioral risk factors associated with central
      obesity and/or inflammation in populations exposed to both obesogenic and
      pathogenic environments remain unclear. OBJECTIVES: We tested which of the
      characteristics distinguished 3 risk groups--high waist-to-height ratio (WHtR;
      >0.5) without inflammation [high-sensitivity C-reactive protein (hs-CRP) <3
      mg/L], normal WHtR (<= 0.5) with inflammation (hs-CRP: 3-10 mg/L), and high WHtR
      with inflammation--from the referent group with normal WHtR without inflammation
      and, secondarily, which factors differed between the groups with high WHtR with
      and without inflammation. METHODS: The analytic sample included 8068 adults
      participating in the China Health and Nutrition Survey in 2009. Adjusted
      multinomial and logistic regression models were used to assess the risk of being
      in one of the "unhealthy" groups compared with the referent group. RESULTS: Men
      with high WHtR with and without inflammation were more likely to live at higher
      urbanicity (57-63%) and have higher incomes (26-42%) and household sanitation (26
      67%) and were >40% less likely to have high physical activity than the healthy
      referent group. Men with high WHtR with inflammation had higher odds of
      infectious symptoms than those with high WHtR without inflammation (OR: 1.73; 95%
      CI: 1.15, 2.61). Women with high WHtR without inflammation were less likely to
      have high household sanitation (44%) or perform high levels of physical activity
      (24%) and were 34% more likely to consume more fiber than the healthy referent
      group. Women with high WHtR and inflammation were more likely than those with
      high WHtR without inflammation to have infectious symptoms (OR: 1.45; 95% CI:
      1.01, 2.07) and less likely to have higher fiber intake (OR: 0.77; 95% CI:
      0.60,1.00) or physical activity (OR: 0.55; 95% CI: 0.41, 0.73). CONCLUSION: These
      results document different underlying pathogenic and obesogenic risk factors for
      visceral adiposity with and without inflammation in Chinese adults, suggesting
      that context-specific approaches may be needed to prevent and treat inflammation.

PMID- 25948782
TI  - A Randomized Trial of Iron-Biofortified Pearl Millet in School Children in India.
AB  - BACKGROUND: Iron deficiency is the most widespread nutritional deficiency in the
      world. OBJECTIVE: The objective of this randomized efficacy trial was to
      determine the effects of iron-biofortified pearl millet (Fe-PM) on iron status
      compared with control pearl millet (Control-PM). METHODS: A randomized trial of
      biofortified pearl millet (Pennisetum glaucum), bred to enhance iron content, was
      conducted in 246 children (12-16 y) for 6 mo in Maharashtra, India. Iron status
      [hemoglobin, serum ferritin (SF), soluble transferrin receptor (sTfR), and total
      body iron (TBI)], inflammation (C-reactive protein and alpha-1 acid
      glycoprotein), and anthropometric indices were evaluated at enrollment and after
      4 and 6 mo. Hodges-Lehmann-Sen 95% CIs were used to examine the effect of the Fe
      PM on iron status compared with commercially available Control-PM. Linear and
      binomial regression models were used to evaluate the effects of Fe-PM on iron
      status and incidence of anemia and iron deficiency, compared with Control-PM.
      RESULTS: At baseline, 41% of children were iron deficient (SF <15 MUg/L) and 28%
      were anemic (hemoglobin <12.0 g/dL). Fe-PM significantly increased SF
      concentrations and TBI after 4 mo compared with Control-PM. Among children who
      were iron deficient at baseline, those who received Fe-PM were 1.64 times more
      likely to become iron replete by 6 mo than were those receiving Control-PM (RR:
      1.64, 95% CI: 1.07, 2.49, P = 0.02). The effects of Fe-PM on iron status were
      greater among children who were iron deficient at baseline than among children
      who were not iron deficient at baseline. CONCLUSIONS: Fe-PM significantly
      improved iron status in children by 4 mo compared with Control-PM. This study
      demonstrated that feeding Fe-PM is an efficacious approach to improve iron status
      in school-age children and it should be further evaluated for effectiveness in a
      broader population context. This trial was registered at clinicaltrials.gov as
      NCT02152150.

PMID- 25948784
TI  - Cheddar Cheese Ripening Affects Plasma Nonesterified Fatty Acid and Serum Insulin
      Concentrations in Growing Pigs.
AB  - BACKGROUND: Meta-analyses of observational studies found cheese consumption to be
      inversely associated with risk of type 2 diabetes and metabolic syndrome. This
      may be attributed to the bioactive compounds produced during cheese ripening.
      OBJECTIVE: The objective of this study was to investigate by means of a porcine
      model how cheeses with different ripening times affect blood glucose, insulin,
      and lipid concentrations and fecal-fat excretion. METHODS: A parallel-arm
      randomized intervention study with 36 Landrace * Yorkshire * Duroc crossbred 3-mo
      old female pigs was conducted. The pigs were fed a 21-d butter-rich run-in diet
      (143 g of butter/kg diet), followed by a 14-d intervention with 1 of 3 isocaloric
      diets: 4-mo ripened cheddar (4-MRC) diet, 14-mo ripened cheddar (14-MRC) diet, or
      24-mo ripened cheddar (24-MRC) diet (350 g of cheese/kg diet). Serum cholesterol,
      triglycerides, HDL cholesterol, LDL cholesterol, and insulin; plasma
      nonesterified fatty acids (NEFAs) and glucose; fecal-fat excretion; and body
      weight were measured. RESULTS: Plasma NEFAs were lower in the 24-MRC (201 +/- 26
      MUEq/L) and in the 14-MRC (171 +/- 19 MUEq/L) diet groups than in the 4-MRC diet
      group (260 +/- 27 MUEq/L; P = 0.044 and P = 0.001). Serum insulin was lower in
      the 24-MRC diet group (1.04 +/- 0.09 mmol/L) than in the 4-MRC diet group (1.44
      +/- 0.14 mmol/L; P = 0.002), but intermediate and not different from either in
      the 14-MRC diet group (1.25 +/- 0.11 mmol/L). Likewise, homeostasis model
      assessment of insulin resistance was lower in the 24-MRC diet group (0.030 +/-
      0.003) than in the 4-MRC diet group (0.041 +/- 0.005; P < 0.01), but intermediate
      and not different from either in the 14-MRC group (0.036 +/- 0.004). CONCLUSIONS:
      Intake of long-term ripened cheddar improved indicators of insulin sensitivity in
      growing pigs compared with short-term ripened cheddar. This may also be important
      for human health.

PMID- 25948783
TI  - A Healthy Lifestyle Score Is Associated with Cardiometabolic and Neuroendocrine
      Risk Factors among Puerto Rican Adults.
AB  - BACKGROUND: Although individual healthy lifestyle behaviors may reduce
      cardiovascular disease risk, few studies have analyzed the combined effect of
      multiple lifestyle components as one all-inclusive measure on such outcomes, much
      less in minority populations. OBJECTIVE: We aimed to develop a Healthy Lifestyle
      Score (HLS) that included several lifestyle recommendations and to test its
      association with metabolic syndrome (MetS) and allostatic load (AL) and their
      cardiometabolic and neuroendocrine factors in Puerto Ricans. METHODS: In a cross
      sectional study in 787 Puerto Ricans living in Boston (aged 45-75 y), we
      developed an HLS that ranged from 0 to 190 (higher score indicative of healthier
      lifestyle) and included 5 components (diet, physical activity and sedentary
      behaviors, smoking, social support and network, and sleep). Multivariable
      adjusted models were used to test associations between the HLS and biomarkers of
      dysregulation and odds of MetS and high AL (>=4 out of 10 components). RESULTS:
      The HLS showed adequate internal consistency (rho = 0.31-0.69) and was inversely
      associated with urinary cortisol (beta +/- SE = -0.22 +/- 0.11; P = 0.042),
      epinephrine (-0.20 +/- 0.09; P = 0.017), and norepinephrine (-0.26 +/- 0.11; P =
      0.016); waist circumference (-0.014 +/- 0.004; P = 0.003); and serum insulin (
      0.30 +/- 0.13; P = 0.028) and positively associated with plasma HDL cholesterol
      (0.007 +/- 0.003; P = 0.021) after adjustment for potential confounders. For each
      20-unit increase in HLS, participants had 19% (95% CI: 2%, 33%) and 25% (11%,
      36%) lower odds of MetS or AL, respectively. Healthier scores for social support
      and network and smoking components were associated with lower odds of high AL (P
      < 0.005). No significant associations were observed for other individual
      lifestyle components. CONCLUSIONS: Following an overall healthy lifestyle that
      comprises a combination of multiple behaviors may provide stronger protection
      against MetS and AL in Puerto Rican adults than individual components. The HLS
      may be a useful tool for examining health-related outcomes. This trial was
      registered at clinicaltrials.gov as NCT01231958.

PMID- 25948785
TI  - The Probiotic Mixture VSL#3 Has Differential Effects on Intestinal Immune
      Parameters in Healthy Female BALB/c and C57BL/6 Mice.
AB  - BACKGROUND: Probiotic bacteria may render mice resistant to the development of
      various inflammatory and infectious diseases. OBJECTIVE: This study aimed to
      identify mechanisms by which probiotic bacteria may influence intestinal immune
      homeostasis in noninflammatory conditions. METHODS: The effect of VSL#3, a
      mixture of 8 probiotic bacteria, on intestinal gene expression was studied in
      healthy female BALB/c and C57BL/6 mice after prolonged oral treatment (28 d,
      triweekly) with 3 * 10(8) colony-forming units of VSL#3. In a separate experiment
      in BALB/c mice, the effects of prolonged administration of VSL#3 and of phosphate
      buffered saline (PBS), followed by 1 single dose of VSL#3, on innate and adaptive
      immune cells were evaluated. RESULTS: Microarray analysis of the intestines of
      mice treated with PBS confirmed well-established differences in the expression of
      immune-related genes between C57BL/6 and BALB/c mice. Prolonged administration of
      VSL#3 was associated with downregulation of Il13 [fold change (FC) = 0.46] and
      Eosinophil peroxidase (Epx) (FC = 0.44) and upregulation of Il12rb1 (FC = 2.1), C
      C chemokine receptor type 5 (Ccr5) (FC = 2.6), chemokine (C-X-C motif) receptor 3
      (Cxcr3) (FC = 1.6), and C-X-C motif chemokine 10 (Cxcl10) (FC = 2.8) in BALB/c
      mice but not in C57BL/6 mice. In BALB/c mice, it was shown that 28 d of treatment
      with VSL#3 affected the Peyer's patches (PPs) and mesenteric lymph nodes (MLNs),
      which was evident from an increase in B cells (26% and 8%, respectively), a
      decrease in T cells (21% and 8%, respectively), and an increase in cluster of
      differentiation (CD) 11c(+) cells (57% in PPs) compared with PBS-treated mice.
      This treatment was also associated with increased frequencies of T helper 17
      (13%) and regulatory T cells (11%) in the MLNs. Treatment with PBS followed by 1
      single dose of VSL#3, 18 h before killing, was associated with a 2-fold increase
      in CD103(+)CD11c(+) dendritic cells in MLNs and PPs. CONCLUSION: VSL#3 treatment
      mediates mouse strain-specific alterations in immunologic phenotype in conditions
      of homeostasis, suggesting that the effects of probiotic bacteria depend on the
      genetic background of the host.

PMID- 25948788
TI  - Whistleblowing in medicine and in Homer's Iliad.
AB  - 'Thinking with Homer', or drawing creatively on themes and scenes from Homer's
      Iliad and Odyssey, can help us to better understand medical culture and practice.
      One current, pressing, issue is the role of the whistleblower, who recognises and
      exposes perceived poor practice or ethical transgressions that compromise patient
      care and safety. Once, whistleblowers were ostracised where medical culture
      closed ranks. However, in a new era of public accountability, medicine looks to
      formally embrace whistleblowing to the point that not reporting transgressions
      can now constitute a transgression of professionalism. Where medical students
      identify with the history and traditions of medical culture, they inevitably find
      themselves in situations of conflicting loyalties if they encounter senior
      clinicians behaving unprofessionally. What are the implications of facing these
      dilemmas for students in terms of role modelling and shaping of character as a
      doctor, and how might a study of Homer help with such dilemmas? We suggest that a
      close reading of an opening scene in Homer's the Iliad can help us to better
      appreciate such ethical dilemmas. We link this with the early Greek tradition of
      parrhesia or 'truth telling', where frankly speaking out against perceived
      injustice is encouraged as resistance to power and inappropriate use of
      authority. We encourage medical educators to openly discuss perceived ethical
      dilemmas with medical students, and medicine as a culture to examine its
      conscience in a transition from an authoritarian to an 'open' society, where
      whistleblowing becomes as acceptable and necessary as good hygiene on the wards. 

PMID- 25948787
TI  - A New Database Facilitates Characterization of Flavonoid Intake, Sources, and
      Positive Associations with Diet Quality among US Adults.
AB  - BACKGROUND: Epidemiologic studies demonstrate inverse associations between
      flavonoid intake and chronic disease risk. However, lack of comprehensive
      databases of the flavonoid content of foods has hindered efforts to fully
      characterize population intakes and determine associations with diet quality.
      OBJECTIVES: Using a newly released database of flavonoid values, this study
      sought to describe intake and sources of total flavonoids and 6 flavonoid classes
      and identify associations between flavonoid intake and the Healthy Eating Index
      (HEI) 2010. METHODS: One day of 24-h dietary recall data from adults aged >= 20 y
      (n = 5420) collected in What We Eat in America (WWEIA), NHANES 2007-2008, were
      analyzed. Flavonoid intakes were calculated using the USDA Flavonoid Values for
      Survey Foods and Beverages 2007-2008. Regression analyses were conducted to
      provide adjusted estimates of flavonoid intake, and linear trends in total and
      component HEI scores by flavonoid intake were assessed using orthogonal
      polynomial contrasts. All analyses were weighted to be nationally representative.
      RESULTS: Mean intake of flavonoids was 251 mg/d, with flavan-3-ols accounting for
      81% of intake. Non-Hispanic whites had significantly higher (P < 0.001) intakes
      of total flavonoids (275 mg/d) than non-Hispanic blacks (176 mg/d) and Hispanics
      (139 mg/d). Tea was the primary source (80%) of flavonoid intake. Regardless of
      whether the flavonoid contribution of tea was included, total HEI score and
      component scores for total fruit, whole fruit, total vegetables, greens and
      beans, seafood and plant proteins, refined grains, and empty calories increased
      (P < 0.001) across flavonoid intake quartiles. CONCLUSIONS: A new database that
      permits comprehensive estimation of flavonoid intakes in WWEIA, NHANES 2007-2008;
      identification of their major food/beverage sources; and determination of
      associations with dietary quality will lead to advances in research on relations
      between flavonoid intake and health. Findings suggest that diet quality, as
      measured by HEI, is positively associated with flavonoid intake.

PMID- 25948786
TI  - Maternal Protein Intake during Pregnancy Is Not Associated with Offspring Birth
      Weight in a Multiethnic Asian Population.
AB  - BACKGROUND: Maternal diet during pregnancy can influence fetal growth. However,
      the relation between maternal macronutrient intake and birth size outcomes is
      less clear. OBJECTIVE: We examined the associations between maternal
      macronutrient intake during pregnancy and infant birth size. METHODS: Pregnant
      women (n = 835) from the Singapore GUSTO (Growing Up in Singapore Towards healthy
      Outcomes) mother-offspring cohort were studied. At 26-28 wk of gestation, the
      macronutrient intake of women was ascertained with the use of 24 h dietary
      recalls and 3 d food diaries. Weight, length, and ponderal index of their
      offspring were measured at birth. Associations were assessed by substitution
      models with the use of multiple linear regressions. RESULTS: Mean +/- SD maternal
      energy intake and percentage energy from protein, fat, and carbohydrates per day
      were 1903 +/- 576 kcal, 15.6% +/- 3.9%, 32.7% +/- 7.5%, and 51.6% +/- 8.7%
      respectively. With the use of adjusted models, no associations were observed for
      maternal macronutrient intake and birth weight. In male offspring, higher
      carbohydrate or fat intake with lower protein intake was associated with longer
      birth length (beta = 0.08 cm per percentage increment in carbohydrate; 95% CI:
      0.04, 0.13; beta = 0.08 cm per percentage increment in fat; 95% CI: 0.02, 0.13)
      and lower ponderal index (beta = -0.12 kg/m(3) per percentage increment in
      carbohydrate; 95% CI: -0.19, -0.05; beta = -0.08 kg/m(3) per percentage increment
      in fat; 95% CI: -0.16, -0.003), but this was not observed in female offspring (P
      interaction < 0.01). CONCLUSIONS: Maternal macronutrient intake during pregnancy
      was not associated with infant birth weight. Lower maternal protein intake was
      significantly associated with longer birth length and lower ponderal index in
      male but not female offspring. However, this finding warrants further
      confirmation in independent studies. This trial was registered at
      clinicaltrials.gov as NCT01174875.

PMID- 25948789
TI  - SEL1L SNP rs12435998, a predictor of glioblastoma survival and response to radio
      chemotherapy.
AB  - The suppressor of Lin-12-like (C. elegans) (SEL1L) is involved in the endoplasmic
      reticulum (ER)-associated degradation pathway, malignant transformation and stem
      cells. In 412 formalin-fixed and paraffin-embedded brain tumors and 39
      Glioblastoma multiforme (GBM) cell lines, we determined the frequency of five
      SEL1L single nucleotide genetic variants with regulatory and coding functions by
      a SNaPShotTM assay. We tested their possible association with brain tumor risk,
      prognosis and therapy. We studied the in vitro cytotoxicity of valproic acid
      (VPA), temozolomide (TMZ), doxorubicin (DOX) and paclitaxel (PTX), alone or in
      combination, on 11 GBM cell lines, with respect to the SNP rs12435998 genotype.
      The SNP rs12435998 was prevalent in anaplastic and malignant gliomas, and in
      meningiomas of all histologic grades, but unrelated to brain tumor risks. In GBM
      patients, the SNP rs12435998 was associated with prolonged overall survival (OS)
      and better response to TMZ-based radio-chemotherapy. GBM stem cells with this SNP
      showed lower levels of SEL1L expression and enhanced sensitivity to VPA.

PMID- 25948790
TI  - Immunoglobulin-like transcript 4 promotes tumor progression and metastasis and up
      regulates VEGF-C expression via ERK signaling pathway in non-small cell lung
      cancer.
AB  - Immunoglobulin-like transcript (ILT) 4 has long been thought to be cell-surface
      molecule in certain immune cells and negatively regulates immune response.
      Recently, overexpression of ILT4 has been observed in a few cancers with unknown
      function. Here, we showed manipulation of ILT4 affected non-small cell lung
      cancer (NSCLC) cell proliferation, migration and invasion in vitro analyses. In
      vivo, ILT4 promoted the tumor growth and metastasis. Furthermore, the
      phosphorylation of extracellular regulated protein kinases (ERK1/2) was enhanced
      in ILT4 overexpressing NSCLC cells. ERK1/2 specific inhibitor U0126 suppressed
      the proliferation, migration and invasion of those cells. Stepwise investigations
      demonstrated that vascular endothelial growth factor C (VEGF-C) was the
      downstream effector of ILT4 and ERK1/2. Silence of VEGF-C attenuated the
      migration and invasion activity of ILT4 overexpressing cells. Moreover, Kaplan
      Meier survival analysis indicated that NSCLC patients with ILT4 positive
      expression had a poor patient survival. ILT4 and VEGF-C expression had notable
      positive correlation in cancer cells, and their co-expression was significantly
      associated with adverse prognostic factors. Our findings suggest that ILT4 drives
      NSCLC development in part on activation of ERK signaling which in turn
      upregulates VEGF-C. ILT4 could be a novel cancer therapeutic target for NSCLC. 

PMID- 25948791
TI  - Anti-tumor activity of selective inhibitors of XPO1/CRM1-mediated nuclear export
      in diffuse malignant peritoneal mesothelioma: the role of survivin.
AB  - Survivin, which is highly expressed and promotes cell survival in diffuse
      malignant peritoneal mesothelioma (DMPM), exclusively relies on exportin 1
      (XPO1/CRM1) to be shuttled into the cytoplasm and perform its anti-apoptotic
      function. Here, we explored the efficacy of Selective Inhibitors of Nuclear
      Export (SINE), KPT-251, KPT-276 and the orally available, clinical stage KPT-330
      (selinexor), in DMPM preclinical models. Exposure to SINE induced dose-dependent
      inhibition of cell growth, cell cycle arrest at G1-phase and caspase-dependent
      apoptosis, which were consequent to a decrease of XPO1/CRM1 protein levels and
      the concomitant nuclear accumulation of its cargo proteins p53 and CDKN1a. Cell
      exposure to SINE led to a time-dependent reduction of cytoplasmic survivin
      levels. In addition, after an initial accumulation, the nuclear protein abundance
      progressively decreased, as a consequence of an enhanced ubiquitination and
      proteasome-dependent degradation. SINE and the survivin inhibitor YM155
      synergistically cooperated in reducing DMPM cell proliferation. Most importantly,
      orally administered SINE caused a significant anti-tumor effect in subcutaneous
      and orthotopic DMPM xenografts without appreciable toxicity. Overall, we have
      demonstrated a marked efficacy of SINE in DMPM preclinical models that may relay
      on the interference with survivin intracellular distribution and function. Our
      study suggests SINE-mediated XPO1/CRM1 inhibition as a novel therapeutic option
      for DMPM. 

PMID- 25948794
TI  - [What has changed in the epidemiology and screening of prostate cancer?].
AB  - OBJECTIVE; The objective of this study is to review the evolution and changes of
      prostate cancer epidemiology and to perform an analysis of the current status of
      prostate cancer screening based on the various studies and scientific societies
      recommendations. METHODS; We performed a bibliographic review of relevant papers
      in relation to prostate cancer epidemiology and screening, with special focus on
      international and multicentric trials on population screening. RESULTS; The
      current number and profile of patients being diagnosed of prostate cancer have
      changed significantly from the pre-PSA era to the present time. Early diagnosis
      and screening strategies have caused an increase in incidence and a decrease in
      cancer mortality in some countries. CONCLUSIONS; Systematic screening, despite
      inconsistencies in some studies, seems to improve prostate cancer specific
      mortality. The introduction of new biomarkers, imaging techniques such as mpMRI
      as well as less aggressive therapeutic alternatives, probably open windows to the
      future for a better diagnosis and treatment of the disease. 

PMID- 25948792
TI  - Leptin signaling enhances cell invasion and promotes the metastasis of human
      pancreatic cancer via increasing MMP-13 production.
AB  - Emerging evidence has suggested that leptin, an adipokine related to energy
      homeostasis, plays a role in cancer growth and metastasis. However, its impact on
      pancreatic cancer is rarely studied. In this study, we found that leptin's
      functional receptor Ob-Rb was expressed in pancreatic cancer cell lines.
      Treatment with leptin enhanced the migration and invasion of pancreatic cancer
      cells but did not affect the proliferation of human pancreatic cancer cells.
      Leptin up-regulated the expression of matrix metalloproteinase-13 (MMP-13) via
      the JAK2/STAT3 signaling pathway. The overexpression of leptin was shown to
      significantly promote tumor growth and lymph node metastasis in a subcutaneous
      model and an orthotopic model of human pancreatic cancer, respectively.
      Furthermore, in human pancreatic cancer tissues, the expression of Ob-Rb was
      positively correlated with the MMP-13 level. The increased expression of either
      Ob-Rb or MMP-13 was significantly associated with lymph node metastasis and
      tended to be associated with the TNM stage in patients with pancreatic cancer.
      Our findings suggest that leptin enhances the invasion of pancreatic cancer
      through the increase in MMP-13 production, and targeting the leptin/MMP-13 axis
      could be an attractive therapeutic strategy for pancreatic cancer.

PMID- 25948793
TI  - Caloric restriction induces heat shock response and inhibits B16F10 cell
      tumorigenesis both in vitro and in vivo.
AB  - Caloric restriction (CR) without malnutrition is one of the most consistent
      strategies for increasing mean and maximal lifespan and delaying the onset of age
      associated diseases. Stress resistance is a common trait of many long-lived
      mutants and life-extending interventions, including CR. Indeed, better protection
      against heat shock and other genotoxic insults have helped explain the pro
      survival properties of CR. In this study, both in vitro and in vivo responses to
      heat shock were investigated using two different models of CR. Murine B16F10
      melanoma cells treated with serum from CR-fed rats showed lower proliferation,
      increased tolerance to heat shock and enhanced HSP-70 expression, compared to
      serum from ad libitum-fed animals. Similar effects were observed in B16F10 cells
      implanted subcutaneously in male C57BL/6 mice subjected to CR. Microarray
      analysis identified a number of genes and pathways whose expression profile were
      similar in both models. These results suggest that the use of an in vitro model
      could be a good alternative to study the mechanisms by which CR exerts its anti
      tumorigenic effects.

PMID- 25948795
TI  - [Current role of protatic specific antigen (PSA) and its by-products in the
      diagnosis of prostate cancer].
AB  - Incorporation of prostatic specific antigen (PSA) to clinical practice was a
      revolution in the diagnosis and modified the epidemiology of prostate cancer
      (PCa). Although it lacks of many characteristics of an ideal tumor marker, it is
      the marker most used for diagnosis and follow up of any kind of cancer. It
      represents the best clinical tool we have available today for screening and
      staging of PCa. On the contrary, its greatest limitation is the lack of tumor
      specificity. The use of PSA by-products and molecular isoforms tries to solve, at
      least partially, its limitations. Indeed, the use of FreePSA ratio (%fPSA) ad PSA
      density (PSAD) increase significantly the specificity of the diagnostic test and,
      the use of derivatives that evaluate time kinetics of PSA (PSA velocity (PSAV)
      and PSA doubling time (PSADT) represents a very useful tool for prognosis
      estimation during treatment and follow up of the disease. The greatest advance
      over the last years comes from the analysis of the predecessor isoform (-2) pPSA
      and the phi Index. Both markers have demonstrated to improve the sensitivity and
      specificity results obtained to date, resulting in a decrease of unnecessary
      biopsies. Probably, with the ongoing development of new markers for PCa , the
      role of PSA on disease diagnosis and staging would be modified in a few years. 

PMID- 25948796
TI  - [Non- PSA serum markers for the diagnosis of PCa].
AB  - Prostate cancer (PCa) is the most common male malignancy in our population. Over
      the past two decades, the prostate specific antigen (PSA) has been widely used
      for screening, diagnosis and monitoring of prostate cancer. Routine use of PSA
      has been continuing subject to controversy due to its limited specificity, which
      is derived from the fact that serum PSA levels are produced in a variety of non
      neoplastic conditions. The shortcomings in sensitivity and specificity of PSA
      have promoted the search for new biomarkers to improve diagnostic performance.
      The ultimate goal is to get those diagnosing clinically significant prostate
      tumors and to individualize treatment in this disease. Among the biomarkers
      studied in prostate cancer we could found tissue biomarkers as well as serum or
      urine biomarkers. In this paper we proceed to review those serum biomarkers not
      related to PSA that have been published in the literature.

PMID- 25948797
TI  - [Update on the diagnosis of PCa in urine. The current role of urine markers].
AB  - Prostate cancer (PCa) is still a main health issue, in fact it is responsible for
      10% of cancer deaths across Europe. The morphology of the prostate gland makes
      urine an ideal sample, non invasive, for determination both diagnostic and
      prognostic biomarkers. We use urinary PCA3 levels to indicate a prostate biopsy,
      and it is the only urinary biomarkers in PCa with FDA approval for clinical use.
      Many other biomarkers based on the expression of specific genes of PCa are being
      studied and validated, for instance the fusion gene TMPRSS2-ERG with a commercial
      kit available, while another approach is to test the expression of a panel of
      genes. An emerging focus of research, which deserves attention, is miRNAs. Other
      newer approaches such as epigenetics, proteomics and metabolomics also would be
      very useful in the future for the development and validation of new biomarkers.
      In this paper we review the state of the art in the field of urinary biomarkers
      in PCa. 

PMID- 25948798
TI  - [Role of tissue markers on diagnosis, prognosis and monitoring of prostate
      cancer].
AB  - Prostate specific antigen has maintained a key role as serum marker for prostate
      cancer (PCa) diagnosis and management since almost 25 years ago. However,
      suboptimal sensitivity and specificity, resulting in missed diagnoses,
      unnecessary prostate biopsies, as well as, detection of clinically indolent
      disease emphasize the need for new biomarkers. OBJECTIVE: The purpose of this
      review is to examine the current status of tissue-based PCa markers, with special
      emphasis on recently marketed assays, and to evaluate their potential advantages
      to improve diagnosis, discriminate between indolent and aggressive disease, as
      well as, their role selecting therapeutic strategies. EVIDENC SYNTHESIS: PubMed
      based available literature provided primarily the core for this review. The more
      recent, larger size series, meta-analysis and frequently referred originals were
      prioritized. Advances in genomics, molecular technologies along with new
      immunohistochemical procedures have enabled the discovery and study of a growing
      number of PCA markers. In the past two years, these efforts have produced assays
      to more accurately detect and characterize the disease. We present the
      development and validation of tissue-based genetic tests, and discuss the
      challenge of incorporating the use of these new markers into clinical practice.
      CONCLUSIONS: Since prostate cancer is a heterogeneous disease, having a defined
      set of markers for early diagnosis, prognosis and follow-up, is clinically
      relevant. Some of these new markers can now be used to complement the
      conventional histopathologic diagnosis, as well as, to help already established
      parameters assessing prognosis.

PMID- 25948799
TI  - [Usefulness of clinical nomograms and predictive models for pca. Predictive
      clinical factors of tumor agressiveness].
AB  - In this narrative review we present the natural evolution of predictive models to
      their presentation in the nomogram format. We show their clinical usefulness and
      the objective parameters that contribute to their clinical use: calibration,
      discrimination, decision curves and probability density functions. We continue
      detailing the various existing predictive models/nomograms in relation to
      prostate cancer aggressiveness before and after biopsy, before and after primary
      treatment, recurrence and castration resistance. Finally we include future
      markers in advanced stage of implementation in the context of nomograms and
      related to the aggressiveness of prostate cancer: PCA3, PHI coefficient, 4Kscore,
      cell cycle progression (Prolaris(r)) and single nucleotid polymorphisms. 

PMID- 25948800
TI  - [Conventional transrectal ultrasound guided biopsy. Current role, indications,
      techniques and limitations].
AB  - OBJECTIVES: The objective of this work is to evaluate the current role of
      conventional transrectal ultrasound guided biopsy of the prostate in the
      diagnosis of cancer. With this aim we review its indications, the various
      techniques, associated complications and limitations of this test. METHODS: We
      performed a bibliographic review through NCBI-PUBMED. We also evaluated the
      information and recommendations of the available clinical guidelines with their
      respective evidence levels. Lastly, some of the appraisals included are based on
      our group's personal experience that has performed more than 7000 prostate
      biopsies with various protocols and methodologies over two decades of health care
      practice. RESULTS: Conventional prostatic biopsies lack precision; they are not
      close to reality in terms of tumor amount, localization and grading. The number
      and localization of the cores to be taken is not clear; there are too many biopsy
      schemes, making it less reliable and reproducible than expected. Although it is a
      good tool, there is an obvious risk of over diagnosis of clinically non
      significant tumors. The lack of standardization of the various biopsy schemes has
      clear prognostic and decision-making implications. Another limitation is the
      scarce number of results attributable to biopsies targeted at ultrasound visible
      lesions. Obviously, the complications, discomfort, and distress generated by
      conventional biopsy and repeated biopsy programs are some of their limitations
      and the reasons for patient rejection. We are in a crossroad where multiple
      groups try to demonstrate the sensitivity and reproducibility of targeting the
      biopsy, by means of various techniques, to the lesions found in multiparametric
      MRI. CONCLUSIONS: Ultrasound guided prostatic biopsy is the main diagnostic
      method for prostate cancer yet. The information it gives is greatly relevant for
      staging, prognostic evaluation and therapeutic decision-making. Nevertheless, its
      limitations are evident: low sensitivity, overdiagnosis, complicacions, patient's
      distress, etc. There are two lines of development to improve its efficiency. The
      one aiming to reduce the number of biopsies and cores by selectively targeting
      the findings of the MRI and the one that continues systematizing schemes with
      increasing number of cores to achieve the optimal sampling. Technical advances,
      such as image fusion, will maybe allow us in the future to translate the MRI
      findings into verified and reproducible clinical results. We must standardize the
      conventional techniques of prostate biopsy in our centers, using protocols and
      making them safe for patients. We must review our results to ensure reasonable
      detection rates, as well as our indications, considering patient's age,
      comorbidities and expectations about therapy. We must include, as far as
      possible, other tools, such as multiparametric MRI to enable biopsy
      rationalization and improve their efficacy.

PMID- 25948801
TI  - Systematic ultrasound-guided saturation and template biopsy of the prostate:
      indications and advantages of extended sampling.
AB  - OBJECTIVES: Prostate biopsy (PB) is the gold standard for the diagnosis of
      prostate cancer (PCa). However, the optimal number of biopsy cores remains
      debatable. We sought to compare contemporary standard (10-12 cores) vs.
      saturation (=18 cores) schemes on initial as well as repeat PB. METHODS: A non
      systematic review of the literature was performed from 2000 through 2013. Studies
      of highest evidence (randomized controlled trials, prospective non-randomized
      studies, and retrospective reports of high quality) comparing standard vs
      saturation schemes on initial and repeat PB were evaluated. Outcome measures were
      overall PCa detection rate, detection rate of insignificant PCa, and procedure
      associated morbidity. RESULTS: On initial PB, there is growing evidence that a
      saturation scheme is associated with a higher PCa detection rate compared to a
      standard one in men with lower PSA levels (<10 ng/ml), larger prostates (>40 cc),
      or lower PSA density values (<0.25 ng/ml/cc). However, these cut-offs are not
      uniform and differ among studies. Detection rates of insignificant PCa do not
      differ in a significant fashion between standard and saturation biopsies. On
      repeat PB, PCa detection rate is likewise higher with saturation protocols.
      Estimates of insignificant PCa vary widely due to differing definitions of
      insignificant disease. However, the rates of insignificant PCa appear to be
      comparable for the schemes in patients with only one prior negative biopsy, while
      saturation biopsy seems to detect more cases of insignificant PCa compared to
      standard biopsy in men with two or more prior negative biopsies. Very extensive
      sampling is associated with a high rate of acute urinary retention, whereas other
      severe adverse events, such as sepsis, appear not to occur more frequently with
      saturation schemes. DISCUSSION: Current evidence suggests that saturation schemes
      are associated with a higher PCa detection rate compared to standard ones on
      initial PB in men with lower PSA levels or larger prostates, and on repeat PB.
      Since most data are derived from retrospective studies, other endpoints such as
      detection rate of insignificant disease - especially on repeat PB - show broad
      variations throughout the literature and must, thus, be interpreted with caution.
      Future prospective controlled trials should be conducted to compare extended
      templates with newer techniques, such as image-guided sampling, in order to
      optimize PCa diagnostic strategy.

PMID- 25948802
TI  - [Advances in ultrasound techniques for the diagnosis and staging of prostate
      cancer. Elastography, Doppler ultrasound, ultrasound contrast media, ultrasound
      quantification media and MRI fusion].
AB  - OBJECTIVES: Transrectal ultrasound-guided prostate biopsy remains the gold
      standard in the diagnosis of prostate cancer. Various Ultrasound modalities have
      been proposed to increase the cancer detection rate. Our purpose is to evaluate
      each of these methods , and to present its current literature and clinical
      utility. METHOD: A non structured review of the current literature was conducted
      over these different various ultrasound modalities used during the transrectal
      ultrasound-guided prostate biopsied in the diagnosis of prostate cancer. RESULTS:
      The data investigation of the various modalities associated sonographic features
      exhibits great heterogeneity and highly variable results. Some new techniques
      sampling present promising results with high sensitivity and specificity, thus
      increasing the diagnostic yield of transrectal biopsy. It seems that elastography
      shows encouraging figures, especially given the recent introduction of the
      "shearvawe" elastography that decreases the user-dependent factor. CONCLUSIONS:
      The ultrasound-guided prostate biopsy has an acceptable sensitivity in the
      diagnosis of prostate cancer, but its specificity is still low. Various
      modalities associated with ultrasound are available in clinical practice in order
      to increase cancer detection rate. Although some promising data have been
      published for some of the modalities, we believe the combination of these
      includes validated ultrasound guided biopsy protocols to accurately target and
      diagnose prostate cancer.

PMID- 25948803
TI  - [Multiparametric MRI. The role of MRI techniques in the diagnosis, staging and
      follow up of prostate cancer].
AB  - The current diagnosis of prostate cancer based on PSA values and systematic
      biopsy has limitations in its efficacy of detection and staging. Technical
      advances on imaging over the last decade, mainly MRI, enable improvements in the
      strategy of prostate cancer management in diagnosis, staging, follow up and
      therapy monitoring. MRI enables the combination of morphological (T2 sequences)
      and, at the same time, functional information by means of the application of
      sequences such as spectroscopy (SMRI), diffusion and dynamic intravenous contrast
      (CMRI) in the same study, giving the multiparametric MRI (mpMRI). Currently, it
      is not necessary to apply all sequences to obtain an mpMR study of optimal
      efficacy, so that a time shorter than 30 minutes is enough to obtain the
      necessary information depending on the clinical indication. The main clinical
      indications of prostatic MRI are a) local, regional or distance staging; b)
      Detection or guide for diagnostic biopsy for clinical risk suspicion or negative
      result in previous biopsies; c) active surveillance; and d) therapeutic
      monitoring. Furthermore, one of the most relevant features of prostate cancer,
      and a challenge for the mpMRI techniques is to be able to differentiate
      aggressive and non-significant neoplasias (latent). This update tries to review
      the current role of mpMRI in the management of prostate cancer using in
      combination the anatomical (T2) and functional (SMRI, DMRI and CMRI) information.
      We also describe the European prostate mpMRI guidelines, PI-RADS (Prostate
      imaging reporting data System).

PMID- 25948804
TI  - [Selection of candidates for prostate biopsy using multiparametric magnetic
      resonance imaging in patients with persistently raising PSA].
AB  - The current diagnosis of prostate cancer is based on randomized prostate biopsies
      to obtain histological material for study, without introducing any imaging
      technique in the diagnostic algorithm. OBJECTIVES: To conduct a literature review
      of the role of multiparametric MRI ( mMRI ) in the diagnosis of prostate cancer,
      and present preliminary data from our series of 233 patients undergoing mRMN and
      transrectal ultrasound (TRUS) prostate biopsy. MATERIAL AND METHODS: We performed
      a PubMed search for those articles that refer to the usefulness of mMRI in the
      follow-up and monitoring of patients with persistently elevated PSA without
      previous biopsies, and those with a previous negative biopsy, and assess the
      power of mRMN for detecting PCa in both the peripheral and the central gland. We
      present the preliminary results of our series, consisting of 233 patients
      selected between 2008 and 2011 undergoing mMRI and TRUS-guided prostatic biopsy
      because of elevated PSA levels or suspicious digital rectal examination. RESULTS:
      We discuss several articles published from 2003 to 2014. We compare our results
      with those from the literature. DISCUSSION: The diagnostic algorithm of prostate
      cancer to date does not include any imaging technique in the decision-making
      process. The mMRI is a functional imaging technique that provides increasing
      evidence in deciding which patients should be biopsied and which patients may
      avoid it despite persisting high levels of PSA. The advantage of this technique
      lies not only in its high detection rate in intermediate and high risk lesions,
      but also in its high specificity. It allows us to avoid diagnosing clinically
      insignificant tumors and thus, avoids overtreatment. CONCLUSION: The mRMN is a
      useful technique not yet incorporated in algorithms of prostate cancer diagnosis
      in urological societies. Its safety, effectiveness and efficiency are forcing to
      include its progressive use and with high probability will be soon incorporated
      into the decision-making charts.

PMID- 25948805
TI  - Integrated US-MR fusion images and MR targeted biopsies. What are their role and
      value in the detection and follow-up of prostate cancer.
AB  - Accuracy of multiparametric MRI has greatly improved the ability of localizing
      tumor foci of prostate cancer. This property can be used to perform a TRUS-MR
      image registration, new technological advance, which allows for an overlay of an
      MRI onto a TRUS image to target a prostate biopsy toward a suspicious area Three
      types of registration have been developed: cognitive-based, sensor-based, and
      organ-based registration. Cognitive registration consists of aiming a suspicious
      area during biopsy with the knowledge of the lesion location identified on
      multiparametric MRI. Sensor-based registration consists of tracking in real time
      the TRUS probe with a magnetic device, achieving a global positioning system
      which overlays in real-time prostate image on both modalities. Organ based
      registration does not aim to track the TRUS probe, but the prostate itself to
      compute in a 3D acquisition the TRUS prostate shape, allowing for a registration
      with the corresponding 3D MRI shape. The concept of an MR-US fusion TB strategy
      only is gaining more and more widespread acceptance. In a TB only strategy, fewer
      men could be biopsied overall, with a greater proportion of men diagnosed with
      clinically significant prostate, as well as fewer men"over diagnosed" with
      clinically insignificant cancer. However, more clinical research is required
      before this strategy is ready for widespread adoption.

PMID- 25948806
TI  - State of the art of PET/CT with 11-choline and 18F-fluorocholine in the diagnosis
      and follow-up of localized and locally advanced prostate cancer.
AB  - OBJECTIVE: To provide an updated state of the art about the role of positron
      emission tomography/computed tomography (PET/CT) with 11C-Choline and 18F
      fluorocholine in the localized and locally advanced Prostate Cancer (PCa) in the
      staging and restaging setting. METHODS: We performed a non-systematic review of
      the literature based on a free-text search in the National Library of Medicine
      Database (MEDLINE) to select English-language published papers evaluating PET and
      PET/CT imaging with radiolabelled choline in initial diagnosis and in post
      treatment phase in PCa patients. RESULTS: PET and PET/CT with 11C-choline and 18F
      fluorocholine have been largely investigated as non-invasive diagnostic tools in
      PCa. Actually, the relatively high rate of false negative findings due to the
      small dimension of neoplastic lesions and the available spatial resolution of PET
      tracers limits the routine use of choline PET and PET/CT in staging setting;
      moreover, it cannot reliably replace the lymph node (LN) dissection for detecting
      LN involvement. On restaging setting, Choline PET/CT showed a higher accuracy
      than conventional imaging modalities, especially in the detection of LN and
      systemic metastases, while it is less accurate than magnetic resonance imaging in
      the detection of local relapse. CONCLUSION: In the Prostate Specific Antigen
      (PSA) era with a large number of localized disease, the diagnostic performance of
      choline PET and PET/CT lack of reliability in initial diagnosis of PCa. The major
      clinical role of choline PET/CT is the re-staging of patients with a biochemical
      relapse after radical treatment; the promising performance of choline PET/CT scan
      in patients with low levels of PSA could also lead the clinicians for to perform
      PET-guided adjuvant curative therapies or palliative treatments in patients
      already treated radically for PCa.

PMID- 25948807
TI  - [Total body MRI in early detection of bone metastasis and its indication in
      comparison to bone scan and other imaging techniques].
AB  - Bone metastases are a recognized prognostic factor in patients with prostate
      cancer. Currently, Tc99 bone scan is the most frequently used imaging technique
      for their detection, showing a high sensitivity but a limited specificity. Thus,
      new morphological and mainly functional imaging techniques based on PET and MRI,
      or hybrid techniques such as PET-CT or PET-MRI have been introduced to improve
      metastases detection, estimation of total tumor load and for therapeutic
      monitoring. In this clinical scenario, total body MRI has arisen as a very
      promising technique in detection and therapeutic monitoring of bone metastases of
      prostate cancer, because it neither uses ionizing radiation nor needs the
      administration of contrast media. The incorporation of MR diffusion to the
      morphologic total body MRI protocols provides functional information, improving
      the sensitivity in oncological lesions detection in general and osteolytic bone
      metastases of PCa in particular. Its integration in protocols with morphological
      sequences and its quantification through ADC maps enables us to better understand
      metastatic bone disease patterns and their changes with different therapies.
      Total body D MRI enables the early classification of the response to treatment
      with evident advantages over other imaging techniques and the purely
      morphological approach with MRI. In any case, prospective and cost-effectiveness
      studies are necessary to establish the role of total-body D MRI in the management
      of patients with PCa.

PMID- 25948808
TI  - [Personalized medicine and prostate cancer. The reality of change].
AB  - Prostate cancer (PCa) is a public health problem in western male populations on
      the basis of it's high incidence and prevalence. Nowadays we come to changes in
      the diagnostic technologies that deserve special attention and that once applied
      allow to show the way towards a personalized view of PCa being able to join this
      modern current trend of the oncologic pathology. In spite of the recognized
      heterogeneity of the disease; clinical, pathological and genetic variants in
      genes and the limitations of the PSA as a biomarker to determine the biological
      aggressiveness of PCa, the certain thing is that the therapeutic final decision
      is adopted on the basis of a distant information to the wished customization and
      it moves excessive uncertainty for patients.In this respect the search based on
      the identification of alterations on the genomic sequence and it's influence in
      the molecular characterization of the PCa is a constant in the investigation
      since nowadays. Actually, the progressive adjournment to the clinic of
      information tumour information that comes from the diagnostic tests related
      genetic material or their biochemical products, though still in initial phase,
      already allows to predict relevant changes in molecular characterization of the
      prostate cancer, in the eventual availability of predictive biomarkers from
      susceptibility to suffer the disease and of the personalized stratification of
      risk across the incorporation of newly and interesting molecular and
      immunohistochemistry biomarkers. Likewise the advances in the perspectives opened
      with the diagnosis, and the relevance in the decisions of biopsy indications that
      stem from it are based on the utilization, with the corresponding merger of
      images, of the multiparametric magnetic resonance (mpMRI) and the new prostate
      ecographic transrectal images with it's natural evolution towards focal
      treatments represent, in spite of the recognized complex interpretation of the
      images, another significant transformation towards the individualization and
      ideally customization of the clinical decisions opposite to a certain patient
      with PCa. Events all of them, even more, if they are considered to be combined
      turn out to be very promising and it's integration brings us over to personalized
      medicine in PCa since already it happens in others, though still small,
      neoplastic diseases. All this aspects are summarized and discussed in the present
      article in the light of the recent communicated information and the reflection
      and personal experience of the authors. Finally chasing how to improve the
      clinical managing and the treatment for patients with PCa.

PMID- 25948809
TI  - Genetic tools for manipulating Acinetobacter baumannii genome: an overview.
AB  - Acinetobacter baumannii is an emerging nosocomial pathogen involved in a variety
      of infections ranging from minor soft-tissue infections to more severe infections
      such as ventilator-associated pneumonia and bacteraemia. A. baumannii has become
      resistant to most of the commonly used antibiotics and multidrug-resistant
      isolates are becoming a severe problem in the healthcare setting. In the past few
      years, whole-genome sequences of >200 A. baumannii isolates have been generated.
      Several methods and molecular tools have been used for genetic manipulation of
      various Acinetobacter spp. Here, we review recent developments of various genetic
      tools used for modification of the A. baumannii genome, including various ways to
      inactivate gene function, chromosomal integration and transposon mutagenesis. 

PMID- 25948810
TI  - The Transcriptome and Terpene Profile of Eucalyptus grandis Reveals Mechanisms of
      Defense Against the Insect Pest, Leptocybe invasa.
AB  - Plants have evolved complex defenses that allow them to protect themselves
      against pests and pathogens. However, there is relatively little information
      regarding the Eucalyptus defensome. Leptocybe invasa is one of the most damaging
      pests in global Eucalyptus forestry, and essentially nothing is known regarding
      the molecular mechanisms governing the interaction between the pest and host. The
      aim of the study was to investigate changes in the transcriptional landscape and
      terpene profile of a resistant and susceptible Eucalyptus genotype in an effort
      to improve our understanding of this interaction. We used RNA-seqencing to
      investigate transcriptional changes following L. invasa oviposition. Expression
      levels were validated using real-time quantitative PCR. Terpene profiles were
      investigated using gas chromatography coupled to mass spectometry on uninfested
      and oviposited leaves. We found 698 and 1,115 significantly differentially
      expressed genes from the resistant and susceptible interactions, respectively.
      Gene Ontology enrichment and Mapman analyses identified putative defense
      mechanisms including cell wall reinforcement, protease inhibitors, cell cycle
      suppression and regulatory hormone signaling pathways. There were significant
      differences in the mono- and sesquiterpene profiles between genotypes and between
      control and infested material. A model of the interaction between Eucalyptus and
      L. invasa was proposed from the transcriptomic and chemical data. 

PMID- 25948811
TI  - A population response analysis approach to assign class II HLA-epitope
      restrictions.
AB  - Identification of the specific HLA locus and allele presenting an epitope for
      recognition by specific TCRs (HLA restriction) is necessary to fully characterize
      the immune response to Ags. Experimental determination of HLA restriction is
      complex and technically challenging. As an alternative, the restricting HLA locus
      and allele can be inferred by genetic association, using response data in an HLA
      typed population. However, simple odds ratio (OR) calculations can be problematic
      when dealing with large numbers of subjects and Ags, and because the same epitope
      can be presented by multiple alleles (epitope promiscuity). In this study, we
      develop a tool, denominated Restrictor Analysis Tool for Epitopes, to extract
      inferred restriction from HLA class II-typed epitope responses. This automated
      method infers HLA class II restriction from large datasets of T cell responses in
      HLA class II-typed subjects by calculating ORs and relative frequencies from
      simple data tables. The program is validated by: 1) analyzing data of previously
      determined HLA restrictions; 2) experimentally determining in selected
      individuals new HLA restrictions using HLA-transfected cell lines; and 3)
      predicting HLA restriction of particular peptides and showing that corresponding
      HLA class II tetramers efficiently bind to epitope-specific T cells. We further
      design a specific iterative algorithm to account for promiscuous recognition by
      calculation of OR values for combinations of different HLA molecules while
      incorporating predicted HLA binding affinity. The Restrictor Analysis Tool for
      Epitopes program streamlines the prediction of HLA class II restriction across
      multiple T cell epitopes and HLA types. 

PMID- 25948812
TI  - Identification of a nuclear export sequence in the MHC CIITA.
AB  - Initiation of an immune response through expression of MHC class II and related
      genes is under the control of the CIITA. Normally found in both the cytoplasm and
      nucleus, CIITA is tightly controlled by a variety of posttranslational
      modifications as well as interactions with other nuclear and cytoplasmic factors,
      whereas disruption of this dual subcellular localization impairs CIITA
      functioning and expression of target genes. Although CIITA has well-defined
      domains necessary for its nuclear import, the region responsible for the
      translocation of CIITA from the nucleus has not been characterized. In this
      study, we identify a leucine-rich motif at residues 717-724 that bears strong
      homology to known nuclear export sequence (NES) domains. Mutation of this region
      renders CIITA insensitive to treatment with leptomycin B, an inhibitor of nuclear
      export, whereas fusion of this domain to a heterologous GFP is sufficient to
      induce its export to the cytoplasm or cause its retention in the nucleus
      following leptomycin B treatment. Point mutations of specific leucine residues
      within the NES disrupt the normal subcellular distribution of the full-length
      CIITA, impair its ability to interact with the nuclear export factor CRM1, and
      enhance CIITA-induced gene expression from an MHC class II gene promoter. IFN
      gamma stimulation of class II genes is further enhanced by inhibiting the nuclear
      export of endogenous CIITA. Collectively, these data demonstrate the first
      identification of a specific NES within CIITA and place it among the other
      protein domains that contribute to the posttranslational regulation of CIITA
      activity.

PMID- 25948813
TI  - Crucial roles of TNFAIP8 protein in regulating apoptosis and Listeria infection.
AB  - TNF-alpha-induced protein 8 (TNFAIP8 or TIPE) is a newly described regulator of
      cancer and infection. However, its precise roles and mechanisms of actions are
      not well understood. We report in this article that TNFAIP8 regulates Listeria
      monocytogenes infection by controlling pathogen invasion and host cell apoptosis
      in a RAC1 GTPase-dependent manner. TNFAIP8-knockout mice were resistant to lethal
      L. monocytogenes infection and had reduced bacterial load in the liver and
      spleen. TNFAIP8 knockdown in murine liver HEPA1-6 cells increased apoptosis,
      reduced bacterial invasion into cells, and resulted in dysregulated RAC1
      activation. TNFAIP8 could translocate to plasma membrane and preferentially
      associate with activated RAC1-GTP. The combined effect of reduced bacterial
      invasion and increased sensitivity to TNF-alpha-induced clearance likely
      protected the TNFAIP8-knockout mice from lethal listeriosis. Thus, by controlling
      bacterial invasion and the death of infected cells through RAC1, TNFAIP8
      regulates the pathogenesis of L. monocytogenes infection.

PMID- 25948814
TI  - Exacerbated experimental colitis in TNFAIP8-deficient mice.
AB  - The TNF-alpha-induced protein 8 (TNFAIP8 or TIPE) is a risk factor for cancer and
      bacterial infection, and its expression is upregulated in a number of human
      cancers. However, its physiologic and pathologic functions are unclear. In this
      study, we describe the generation of TIPE-deficient mice and their increased
      sensitivity to colonic inflammation. TIPE-deficient mice were generated by germ
      line gene targeting and were born without noticeable developmental abnormalities.
      Their major organs, including lymphoid organs and intestines, were
      macroscopically and microscopically normal. However, after drinking dextran
      sodium sulfate-containing water, TIPE-deficient mice developed more severe
      colitis than wild type mice did, as demonstrated by decreased survival rates,
      increased body weight loss, and enhanced leukocyte infiltration, bacterial
      invasion, and inflammatory cytokine production in the colon. Bone marrow chimeric
      experiments revealed that TIPE deficiency in nonhematopoietic cells was
      responsible for the exacerbated colitis in TIPE-deficient mice. Consistent with
      this result, TIPE-deficient intestinal epithelial cells had increased rate of
      cell death and decreased rate of proliferation as compared with wild type
      controls. These findings indicate that TIPE plays an important role in
      maintaining colon homeostasis and in protecting against colitis.

PMID- 25948815
TI  - Species-specific differences in the expression and regulation of alpha4beta7
      integrin in various nonhuman primates.
AB  - Among nonhuman primates, SIV-infected Asian pigtailed macaques (PM) are
      relatively more susceptible to infection and disease progression than SIV
      infected rhesus macaques (RM). In addition, SIV-infected African natural hosts
      such as the sooty mangabeys (SM) are resistant to disease. The mechanisms
      associated with such species-related variable clinical outcomes remain ill
      defined but hold the potential to provide insights into the underlying mechanisms
      surrounding HIV pathogenesis. Recent findings indicate that the expression of the
      heterodimeric gut homing integrin alpha4beta7 can influence both susceptibility
      and disease progression in RM. It was reasoned that differences in the
      frequencies/surface densities of alpha4beta7-expressing lymphocytes might
      contribute to the differences in the clinical outcome of SIV infection among
      NHPs. In this article, we report that CD4(+) T cells from PM constitutively
      express significantly higher levels of alpha4beta7 than RM or SM. Retinoic acid,
      a key regulator of alpha4beta7 expression, was paradoxically found at higher
      levels in the plasma of SM versus RM or PM. We also observed pairing of beta7
      with alphaE (alphaEbeta7) on CD4(+) T cells in the peripheral blood of SM, but
      not PM or RM. Finally, the differential mean density of expression of alpha4beta7
      in RM versus SM versus PM was predominantly dictated by species-specific sequence
      differences at the level of the beta7 promoters, as determined by in vitro
      reporter/promoter construct transfection studies. We propose that differences in
      the regulation and expression of alpha4beta7 may explain, in part, the
      differences in susceptibility and SIV disease progression in these NHP models.

PMID- 25948816
TI  - Regulation of neutrophilic inflammation by proteinase-activated receptor 1 during
      bacterial pulmonary infection.
AB  - Neutrophils are key effector cells of the innate immune response to pathogenic
      bacteria, but excessive neutrophilic inflammation can be associated with
      bystander tissue damage. The mechanisms responsible for neutrophil recruitment to
      the lungs during bacterial pneumonia are poorly defined. In this study, we focus
      on the potential role of the major high-affinity thrombin receptor, proteinase
      activated receptor 1 (PAR-1), during the development of pneumonia to the common
      lung pathogen Streptococcus pneumoniae. Our studies demonstrate that neutrophils
      were indispensable for controlling S. pneumoniae outgrowth but contributed to
      alveolar barrier disruption. We further report that intra-alveolar coagulation
      (bronchoalveolar lavage fluid thrombin-antithrombin complex levels) and PAR-1
      immunostaining were increased in this model of bacterial lung infection.
      Functional studies using the most clinically advanced PAR-1 antagonist,
      SCH530348, revealed a key contribution for PAR-1 signaling in influencing
      neutrophil recruitment to lung airspaces in response to both an invasive and
      noninvasive strain of S. pneumoniae (D39 and EF3030) but that PAR-1 antagonism
      did not impair the ability of the host to control bacterial outgrowth. PAR-1
      antagonist treatment significantly decreased pulmonary levels of IL-1beta, CXCL1,
      CCL2, and CCL7 and attenuated alveolar leak. Ab neutralization studies further
      demonstrated a nonredundant role for IL-1beta, CXCL1, and CCL7 in mediating
      neutrophil recruitment in response to S. pneumoniae infection. Taken together,
      these data demonstrate a key role for PAR-1 during S. pneumoniae lung infection
      that is mediated, at least in part, by influencing multiple downstream
      inflammatory mediators.

PMID- 25948817
TI  - Determinants of gliadin-specific T cell selection in celiac disease.
AB  - In HLA-DQ8-associated celiac disease (CD), the pathogenic T cell response is
      directed toward an immunodominant alpha-gliadin-derived peptide (DQ8-glia
      alpha1). However, our knowledge of TCR gene usage within the primary intestinal
      tissue of HLA-DQ8 (+) CD patients is limited. We identified two populations of
      HLA-DQ8-glia-alpha1 tetramer(+) CD4(+) T cells that were essentially undetectable
      in biopsy samples from patients on a gluten-free diet but expanded rapidly and
      specifically after antigenic stimulation. Distinguished by expression of TRBV9,
      both T cell populations displayed biased clonotypic repertoires and reacted
      similarly against HLA-DQ8-glia-alpha1. In particular, TRBV9 paired most often
      with TRAV26-2, whereas the majority of TRBV9(-) TCRs used TRBV6-1 with no clear
      TRAV gene preference. Strikingly, both tetramer(+)/TRBV9(+) and
      tetramer(+)/TRBV9(-) T cells possessed a non-germline-encoded arginine residue in
      their CDR3alpha and CDR3beta loops, respectively. Comparison of the crystal
      structures of three TRBV9(+) TCRs and a TRBV9(-) TCR revealed that, as a result
      of distinct TCR docking modes, the HLA-DQ8-glia-alpha1 contacts mediated by the
      CDR3-encoded arginine were almost identical between TRBV9(+) and TRBV9(-) TCRs.
      In all cases, this interaction centered on two hydrogen bonds with a specific
      serine residue in the bound peptide. Replacement of serine with alanine at this
      position abrogated TRBV9(+) and TRBV9(-) clonal T cell proliferation in response
      to HLA-DQ8-glia-alpha1. Gluten-specific memory CD4(+) T cells with structurally
      and functionally conserved TCRs therefore predominate in the disease-affected
      tissue of patients with HLA-DQ8-mediated CD.

PMID- 25948818
TI  - De novo-induced self-antigen-specific Foxp3+ regulatory T cells impair the
      accumulation of inflammatory dendritic cells in draining lymph nodes.
AB  - Foxp3(+) regulatory T cell (Treg)-based immunotherapy holds promise for
      autoimmune diseases. However, this effort has been hampered by major caveats,
      including the low frequency of autoantigen-specific Foxp3(+) Tregs and lack of
      understanding of their molecular and cellular targets, in an unmanipulated wild
      type (WT) immune repertoire. In this study, we demonstrate that infusion of
      myelin in WT mice results in the de novo induction of myelin-specific Foxp3(+)
      Tregs in WT mice and amelioration of experimental autoimmune encephalomyelitis.
      Myelin-specific Foxp3(+) Tregs exerted their effect both by diminishing Ag
      bearing inflammatory dendritic cell (iDC) recruitment to lymph nodes and by
      impairing their function. Transcriptome analysis of ex vivo-isolated Treg-exposed
      iDCs showed significant enrichment of transcripts involved in functional
      properties of iDCs, including chemotaxis-related genes. To this end, CCR7
      expression by iDCs was significantly downregulated in tolerant mice and this was
      tightly regulated by the presence of IL-10. Collectively, our data demonstrate a
      novel model for deciphering the Ag-specific Foxp3(+) Treg-mediated mechanisms of
      tolerance and delineate iDCs as a Foxp3(+) Treg cellular target in unmanipulated
      mice.

PMID- 25948819
TI  - Skeletal muscle AMPK is essential for the maintenance of FNDC5 expression.
AB  - Fibronectin type III domain-containing protein 5 (FNDC5) expression is controlled
      by the transcriptional co-activator, peroxisome proliferator-activated receptor
      gamma, coactivator 1 alpha (PGC1alpha). FNDC5 expression has been shown to be
      increased in muscle in response to endurance exercise in some but not all
      studies, therefore a greater understanding of the mechanisms controlling this
      process are needed. The AMP-activated protein kinase (AMPK) is activated by
      exercise in an intensity dependent manner and is an important regulator of
      PGC1alpha activity; therefore, we explored the role of AMPK in the regulation of
      FNDC5 using AMPK beta1beta2 double muscle-null mice (AMPK DMKO), which lack
      skeletal muscle AMPK activity. We found that FNDC5 expression is dramatically
      reduced in resting muscles of AMPK DMKO mice compared to wild-type littermates.
      In wild-type mice, activating phosphorylation of AMPK was elevated immediately
      post contraction and was abolished in muscle from AMPK DMKO mice. In contrast,
      PGC1alpha was increased in both wild-type and AMPK DMKO mice 3 h post contraction
      but FNDC5 protein expression was not altered. Lastly, acute or chronic activation
      of AMPK with the pharmacological AMPK activator AICAR did not increase PGC1alpha
      or FNDC5 expression in muscle. These data indicate that skeletal muscle AMPK is
      required for the maintenance of basal FNDC5 expression. 

PMID- 25948820
TI  - Genetic and phenotypic differentiation of an Andean intermediate altitude
      population.
AB  - Highland populations living permanently under hypobaric hypoxia have been subject
      of extensive research because of the relevance of their physiological adaptations
      for the understanding of human health and disease. In this context, what is
      considered high altitude is a matter of interpretation and while the adaptive
      processes at high altitude (above 3000 m) are well documented, the effects of
      moderate altitude (below 3000 m) on the phenotype are less well established. In
      this study, we compare physiological and anthropometric characteristics as well
      as genetic variations in two Andean populations: the Calchaquies (2300 m) and
      neighboring Collas (3500 m). We compare their phenotype and genotype to the sea
      level Wichi population. We measured physiological (heart rate, oxygen saturation,
      respiration rate, and lung function) as well as anthropometric traits (height,
      sitting height, weight, forearm, and tibia length). We conducted genome-wide
      genotyping on a subset of the sample (n = 74) and performed various scans for
      positive selection. At the phenotypic level (n = 179), increased lung capacity
      stood out in both Andean groups, whereas a growth reduction in distal limbs was
      only observed at high altitude. At the genome level, Calchaquies revealed strong
      signals around PRKG1, suggesting that the nitric oxide pathway may be a target of
      selection. PRKG1 was highlighted by one of four selection tests among the top
      five genes using the population branch statistic. Selection tests results of
      Collas were reported previously. Overall, our study shows that some phenotypic
      and genetic differentiation occurs at intermediate altitude in response to
      moderate lifelong selection pressures. 

PMID- 25948821
TI  - Subdiaphragmatic vagus nerve activity and hepatic venous glucose are
      differentially regulated by the central actions of insulin in Wistar and SHR.
AB  - Glucose is the most important energy substrate for the maintenance of tissues
      function. The liver plays an essential role in the control of glucose production,
      since it is able to synthesize, store, and release glucose into the circulation
      under different situations. Hormones like insulin and catecholamines influence
      hepatic glucose production (HGP), but little is known about the role of the
      central actions of physiological doses of insulin in modulating HGP via the
      autonomic nervous system in nonanesthetized rats especially in SHR where we see a
      high degree of insulin resistance and metabolic dysfunction. Wistar and SHR
      received ICV injection of insulin (100 nU/MUL) and hepatic venous glucose
      concentration (HVGC) was monitored for 30 min, as an indirect measure of HGP. At
      10 min after insulin injection, HVGC decreased by 27% in Wistar rats, with a
      negligible change (3%) in SHR. Pretreatment with atropine totally blocked the
      reduction in HVGC, while pretreatment with propranolol and phentolamine induced a
      decrease of 8% in HVGC after ICV insulin injection in Wistar. Intracarotid
      infusion of insulin caused a significant increase in subdiaphragmatic vagus nerve
      (SVN) activity in Wistar (12 +/- 2%), with negligible effects on the lumbar
      splanchnic sympathetic nerve (LSSN) activity (-6 +/- 3%). No change was observed
      in SVN (-2 +/- 2%) and LSSN activities (2 +/- 3%) in SHR after ICA insulin
      infusion. Taken together, these results show, in nonanesthetized animals, the
      importance of the parasympathetic nervous system in controlling HVGC, and
      subdiaphragmatic nerve activity following central administration of insulin; a
      mechanism that is impaired in the SHR. 

PMID- 25948822
TI  - Effect of daytime-restricted feeding in the daily variations of liver metabolism
      and blood transport of serotonin in rat.
AB  - The biogenic amine serotonin is a signaling molecule in the gastrointestinal
      tract, platelets, and nervous tissue. In nervous system, serotonin and its
      metabolites are under the control of the circadian timing system, but it is not
      known if daily variations of serotonin exist in the liver. To explore this
      possibility, we tested if the rhythmic pattern of serotonin metabolism was
      regulated by daytime restricted feeding (DRF) which is a protocol associated to
      the expression of the food entrained oscillator (FEO). The DRF involved food
      access for 2 h each day for 3 weeks. Control groups included food ad libitum (AL)
      as well as acute fasting and refeeding. Serotonin-related metabolites were
      measured by high pressure liquid chromatography, the anabolic and catabolic
      enzymes were evaluated by western blot, qPCR, and immunohistochemistry to
      generate 24-h profiles. The results showed in the AL group, liver serotonin,
      tryptophan hydroxylase-1 activity, and protein abundance as well as serotonin in
      plasma and serum were rhythmic and coordinated. The DRF protocol disrupted this
      coordinated response and damped the rhythmic profile of these parameters. We
      demonstrated the daily synthesis and the degradation of serotonin as well as its
      transport in blood. This rhythm could influence the physiological role played by
      serotonin in peripheral organs. DRF caused an uncoordinated response in the liver
      and blood serotonin rhythm. This modification could be a part of the physiology
      of the FEO. 

PMID- 25948823
TI  - Combined effects of depleted uranium and ionising radiation on zebrafish embryos.
AB  - In the environment, living organisms are exposed to a mixture of stressors, and
      the combined effects are deemed as multiple stressor effects. In the present
      work, the authors studied the multiple stressor effect in embryos of the
      zebrafish (Danio rerio) from simultaneous exposure to alpha particles and
      depleted uranium (DU) through quantification of apoptotic signals at 24 h post
      fertilisation (hpf) revealed by vital dye acridine orange staining. In each set
      of experiments, dechorionated zebrafish embryos were divided into 4 groups, each
      having 10 embryos: Group (C) in which the embryos did not receive any further
      treatment; Group (IU) in which the embryos received an alpha-particle dose of
      0.44 mGy at 5 hpf and were then exposed to 100 ug l(-1) of DU from 5 to 6 hpf;
      Group (I) in which the embryos received an alpha-particle dose of 0.44 mGy at 5
      hpf and Group (U) in which the dechorionated embryos were exposed to 100 ug l(-1)
      of DU from 5 to 6 hpf. The authors confirmed that an alpha-particle dose of 0.44
      mGy and a DU exposure for 1 h separately led to hormetic and toxic effects
      assessed by counting apoptotic signals, respectively, in the zebrafish.
      Interestingly, the combined exposure led to an effect more toxic than that caused
      by the DU exposure alone, so effectively DU changed the beneficial effect
      (hormesis) brought about by alpha-particle irradiation into an apparently toxic
      effect. This could be explained in terms of the promotion of early death of cells
      predisposed to spontaneous transformation by the small alpha-particle dose (i.e.
      hormetic effect) and the postponement of cell death upon DU exposure. 

PMID- 25948824
TI  - Estimation of 85Kr dispersion from the spent nuclear fuel reprocessing plant in
      Rokkasho, Japan, using an atmospheric dispersion model.
AB  - The spent nuclear fuel reprocessing plant of Japan Nuclear Fuel Limited (JNFL)
      located in Rokkasho, Japan, discharged small amounts of (85)Kr into the
      atmosphere during final tests of the plant with actual spent fuel from 31 March
      2006 to October 2008. During this period, the gamma-ray dose rates due to
      discharged (85)Kr were higher than the background rates measured at the Institute
      for Environmental Sciences and at seven monitoring stations of the Aomori
      prefectural government and JNFL. The dispersion of (85)Kr was simulated by means
      of the fifth-generation Penn State/NCAR Mesoscale Model and the CG-MATHEW/ADPIC
      models (ver. 5.0) with a vertical terrain-following height coordinate. Although
      the simulated gamma-ray dose rates due to discharged (85)Kr agreed fairly well
      with measured rates, the agreement between the estimated monthly mean (85)Kr
      concentrations and the observed concentrations was poor. Improvement of the
      vertical flow of air may lead to better estimation of (85)Kr dispersion. 

PMID- 25948825
TI  - Reference instruments based on spectrometric measurement with Lucas Cells.
AB  - The Bundesamt fur Strahlenschutz (Berlin, Germany) and the Paul Scherrer
      Institute (Villigen, Switzerland) both operate accredited calibration
      laboratories for radon gas activity concentration. Both the institutions use
      Lucas Cells as detector in their reference instrumentation due to the low
      dependence of this detector type on variations in environmental conditions. As a
      further measure to improve the quality of the reference activity concentration, a
      spectrometric method of data evaluation has been applied. The electric pulses
      from the photomultiplier tube coupled to the Lucas Cells are subjected to a pulse
      height analysis. The stored pulse height spectra are analysed retrospectively to
      compensate for fluctuations in the electric parameters of the instrumentation
      during a measurement. The reference instrumentation of both the laboratories is
      described with the respective spectrum evaluation procedures. The methods of
      obtaining traceability to the primary calibration laboratories of Germany and
      Switzerland and data of performance tests are presented. 

PMID- 25948826
TI  - Scavenging of hydroxyl radicals generated in human plasma following X-ray
      irradiation.
AB  - There are various antioxidant materials that scavenge free radicals in human
      plasma. It is possible that the radical-scavenging function causes a radiation
      protective effect in humans. This study estimated the hydroxyl (OH) radical
      scavenging activity induced by X-ray irradiation in human plasma. The test
      subjects included 111 volunteers (75 males and 36 females) ranging from 22 to 35
      years old (average, 24.0). OH radicals generated in irradiated human plasma were
      measured by electron spin resonance (ESR). The relationships between the amount
      of the OH radical and chemical and biological parameters [total protein, total
      cholesterol, triglycerides and hepatitis B surface (HBs) antibodies] were
      estimated in the plasma of the 111 volunteers by a multivariate analysis. The
      presence of HBs antibodies had the greatest influence on OH radical-scavenging
      activity. One volunteer who did not have the HBs antibody was given an
      inoculation of the hepatitis B vaccine. There was a remarkable decrease in the
      amount of OH radical generated from plasma after the HBs antibody was produced.
      The results indicate that the HBs antibody is an important factor for the
      scavenging of OH radicals initiated by X-ray irradiation in the human body. 

PMID- 25948827
TI  - Analysis of internal exposure associated with consumption of crops and
      groundwater from the high background radiation area of Mrima Hill, Kenya.
AB  - Specific concentrations of (226)Ra, (232)Th and (40)K were measured in cassava
      tubers, cassava leaves and groundwater obtained from the high background
      radiation area of Mrima hill and used in the evaluation of the ingested dose.
      Cassava tubers, cassava leaves and groundwater registered average (226)Ra
      concentrations of 60 +/- 5, 141 +/- 11 and 4.3 +/- 0.3 Bq kg(-1), respectively.
      (232)Th was not detected in cassava leaves although it was present in cassava
      tubers as well as in groundwater in average concentrations of 35.3+/-61.5 and
      2.0+/-0.1 Bq kg(-1), respectively. (40)K was present in all samples in average
      concentrations of 842+/-539 Bq kg(-1) in cassava tubers, 1708 +/- 552 Bq kg(-1)
      in cassava leaves and 91.4 Bq kg(-1) in groundwater. The total annual effective
      dose due to ingestion was found to be 7.9 mSv y(-1) of which 2.4 mSv y(-1) was
      due to cassava tubers, 3.8 mSv y(-1) due to cassava leaves and 1.7 mSv y(-1) due
      to water. 

PMID- 25948828
TI  - A Bonner Sphere Spectrometer for pulsed fields.
AB  - The use of conventional Bonner Sphere Spectrometers (BSS) in pulsed neutron
      fields (PNF) is limited by the fact that proportional counters, usually employed
      as the thermal neutron detectors, suffer from dead time losses and show severe
      underestimation of the neutron interaction rate, which leads to strong distortion
      of the calculated spectrum. In order to avoid these limitations, an innovative
      BSS, called BSS-LUPIN, has been developed for measuring in PNF. This paper
      describes the physical characteristics of the device and its working principle,
      together with the results of Monte Carlo simulations of its response matrix. The
      BSS-LUPIN has been tested in the stray neutron field at the CERN Proton
      Synchrotron, by comparing the spectra obtained with the new device, the
      conventional CERN BSS and via Monte Carlo simulations. 

PMID- 25948829
TI  - Calibration of the Politrack(r) system based on CR39 solid-state nuclear track
      detectors for passive indoor radon concentration measurements.
AB  - Swiss national requirements for measuring radon gas exposures demand a lower
      detection limit of 50 kBq h m(-3), representing the Swiss concentration average
      of 70 Bq m(-3) over a 1-month period. A solid-state nuclear track detector
      (SSNTD) system (Politrack, Mi.am s.r.l., Italy) has been acquired to fulfil these
      requirements. This work was aimed at the calibration of the Politrack system with
      traceability to international standards and the development of a procedure to
      check the stability of the system. A total of 275 SSNTDs was exposed to 11
      different radon exposures in the radon chamber of the Secondary Calibration
      Laboratory at the Paul Scherrer Institute, Switzerland. The exposures ranged from
      50 to 15000 kBq h m(-3). For each exposure of 20 detectors, 5 SSNTDs were used to
      monitor possible background exposures during transport and storage. The response
      curve and the calibration factor of the whole system were determined using a
      Monte Carlo fitting procedure. A device to produce CR39 samples with a reference
      number of tracks using a (241)Am source was developed for checking the long-term
      stability of the Politrack system. The characteristic limits for the detection of
      a possible system drift were determined following ISO Standard 11929. 

PMID- 25948830
TI  - Discrimination between natural and other gamma ray sources from environmental
      gamma ray dose rate monitoring data.
AB  - In this study, a method to discriminate between natural and other gamma-ray
      sources from environmental gamma-ray dose rate monitoring data was developed, and
      it was successfully applied to actual monitoring data around nuclear facilities.
      The environmental dose rate is generally monitored by NaI(Tl) detector systems in
      the low dose rate range. The background dose rate varies mainly as a result of
      the deposition of (222)Rn progeny in precipitation and shielding of the ground by
      snow cover. Increments in the environmental dose rate due to radionuclides
      released from nuclear facilities must be separated from these background
      variations. The method in the present study corrects for the dose rate variations
      from natural sources by multiple regression analysis based on the gamma-ray
      counting rates of single-channel analysers opened in the energy ranges of gamma
      rays emitted by (214)Bi and (208)Tl. Assuming a normal distribution of the
      results and using the one-sided type I error of 0.01 while ignoring the type II
      error, the detection limit of the gamma-ray dose rate from artificial sources was
      0.77 nGy h(-1). 

PMID- 25948831
TI  - FWT and OBT concentrations in pine needle samples collected at Toki, Japan (1998
      2012).
AB  - Free water tritium (FWT) and organically bound tritium (OBT) concentrations in
      pine needles have been investigated to understand the regional background tritium
      concentration in Toki City. Samples were regularly collected from pine trees on
      the National Institute for Fusion Science campus (1998-2012) and the nearby
      Shiomi Park (SP; 2002-12). FWT and OBT concentrations of the former samples
      ranged from 0.33 to 0.92 and 0.41 to 1.10 Bq l(-1), respectively, while those of
      the latter samples ranged from 0.32 to 0.86 and 0.33 to 0.79 Bq l(-1),
      respectively. Results of both sampling sites were almost the same, and they have
      been gradually decreased year by year. Concentration level of tritium for Toki
      City was close to the average background level in Japan. The OBT/FWT ratios were
      almost 1.0. The apparent half-life of FWT in this period was estimated as almost
      10 y, and that of OBT was estimated as almost 12 y; these values were almost the
      same as the physical half-life. 

PMID- 25948832
TI  - Injury to the blood-testis barrier after low-dose-rate chronic radiation exposure
      in mice.
AB  - Exposure to ionising radiation induces male infertility, accompanied by
      increasing permeability of the blood-testis barrier. However, the effect on male
      fertility by low-dose-rate chronic radiation has not been investigated. In this
      study, the effects of low-dose-rate chronic radiation on male mice were
      investigated by measuring the levels of tight-junction-associated proteins (ZO-1
      and occludin-1), Niemann-Pick disease type 2 protein (NPC-2) and antisperm
      antibody (AsAb) in serum. BALB/c mice were exposed to low-dose-rate radiation
      (3.49 mGy h(-1)) for total exposures of 0.02 (6 h), 0.17 (2 d) and 1.7 Gy (21 d).
      Based on histological examination, the diameter and epithelial depth of
      seminiferous tubules were significantly decreased in 1.7-Gy-irradiated mice.
      Compared with those of the non-irradiated group, 1.7-Gy-irradiated mice showed
      significantly decreased ZO-1, occludin-1 and NPC-2 protein levels, accompanied
      with increased serum AsAb levels. These results suggest potential blood-testis
      barrier injury and immune infertility in male mice exposed to low-dose-rate
      chronic radiation. 

PMID- 25948833
TI  - A discussion on NORM guidelines: proposed revisions needed for practical use.
AB  - International awareness of NORM as a potential source of radiation risk to
      workers, members of the public and the environment has increased significantly in
      recent years. NORM guidelines were originally developed for radiation management
      in NORM industries. However, the guidelines have been often consulted by many
      other industries not commonly considered as an NORM industry. In addition, with
      the increased awareness of NORM issues, more and more people have tried to apply
      NORM guidelines in many other situations related to NORM in the environment. The
      broad use of NORM guidelines out of the original scope has demonstrated the needs
      to revise the guidelines for practical use. These needs are discussed in the
      article. 

PMID- 25948834
TI  - Measuring radon concentrations and estimating dose in tourist caves.
AB  - Caves and mines are considered to be places of especial risk of exposure to
      (222)Rn. This is particularly important for guides and workers, but also for
      visitors. In the Extremadura region (Spain), there are two cave systems in which
      there are workers carrying out their normal everyday tasks. In one, visits have
      been reduced to maintain the conditions of temperature and humidity. The other
      comprises several caves frequently visited by school groups. The caves were
      radiologically characterised in order to estimate the dose received by workers or
      possible hazards for visitors. 

PMID- 25948835
TI  - A numerical method to optimise the spatial dose distribution in carbon ion
      radiotherapy planning.
AB  - The authors describe a numerical algorithm to optimise the entrance spectra of a
      composition of pristine carbon ion beams which delivers a pre-assumed dose-depth
      profile over a given depth range within the spread-out Bragg peak. The physical
      beam transport model is based on tabularised data generated using the SHIELD
      HIT10A Monte-Carlo code. Depth-dose profile optimisation is achieved by
      minimising the deviation from the pre-assumed profile evaluated on a regular grid
      of points over a given depth range. This multi-dimensional minimisation problem
      is solved using the L-BFGS-B algorithm, with parallel processing support. Another
      multi-dimensional interpolation algorithm is used to calculate at given beam
      depths the cumulative energy-fluence spectra for primary and secondary ions in
      the optimised beam composition. Knowledge of such energy-fluence spectra for each
      ion is required by the mixed-field calculation of Katz's cellular Track Structure
      Theory (TST) that predicts the resulting depth-survival profile. The optimisation
      algorithm and the TST mixed-field calculation are essential tools in the
      development of a one-dimensional kernel of a carbon ion therapy planning system.
      All codes used in the work are generally accessible within the libamtrack open
      source platform. 

PMID- 25948836
TI  - Cytogenetic dosimetry by micronucleus assay using peripheral blood cells is
      modified by thyroid hormones.
AB  - Cytokinesis-block micronucleus (CBMN) assay is a convenient and easy method of
      radiation biodosimetry that uses peripheral blood (PB) cells. However, for
      micronuclei (MN) frequency induced by ionising radiation, a dose-response
      relationship in abnormal condition, such as in cancer patients, has not been
      assessed. To clarify the difference between the dose-response curve generated by
      the CBMN assay in conditions when thyroid hormone levels were normal and during
      thyroid hormone withdrawal (THW) prior to (131)I treatment, 12 thyroid cancer
      patients who underwent thyroidectomy were studied. The collected PB mononuclear
      cells were exposed to 0.5-3.0 Gy X-ray irradiation. Under normal conditions, dose
      dependency and independency of MN frequency were observed in 92 % and 8 %,
      respectively. In contrast, during THW, the number of patients who showed dose
      independency significantly increased to 42 % in comparison with control.
      Furthermore, a higher concentration of serum thyroglobulin in dose-independent
      patients was observed. These results suggest that MN frequency in cytogenetic
      dosimetry is affected by thyroid hormones. 

PMID- 25948837
TI  - Cardiovascular disease mortality of A-bomb survivors and the healthy survivor
      selection effect.
AB  - The latest A-bomb survivor data for cardiovascular diseases are analysed to
      investigate whether in the first years after the bombings the baseline rates of
      proximal survivors were markedly different compared with those of the distal
      survivors. This phenomenon relates to a healthy survivor selection effect. This
      question is important for the decision whether to include or exclude the early
      years of follow-up when analysing the biological effects from acute low and high
      dose exposures following the nuclear weapons explosions in Hiroshima and
      Nagasaki. The present study shows that for cerebrovascular diseases and heart
      diseases the baseline rates are not significantly different in the first two
      decades of follow-up. Thus, for these two detrimental health outcomes, there is
      no need to exclude distal survivors and the first decades of follow-up time when
      investigating the shapes of the related dose-responses. 

PMID- 25948838
TI  - Development of calibration facility for radon and its progenies at NIM (China).
AB  - Accurate measurement of radon and its progenies is the basis to control the radon
      dose and reduce the risk of lung cancer caused. The precise calibration of
      measuring instrument is an important part of the quality control of measurements
      of the concentration of radon and radon progenies. To establish Chinese national
      standards and realise reliable calibrations of measuring instrument for radon and
      its progenies, a radon chamber with regulation capability of environmental
      parameters, aerosol and radon concentrations was designed and constructed at
      National Institute of Metrology (NIM). The chamber has a total volume of ~20 m(3)
      including an exposure volume of 12.44 m(3). The radon concentration can be
      controlled from 12 Bq m(-3) to the maximum of 232 kBq m(-3). The regulation range
      of temperature, relative humidity and aerosol are 0.66 -44.39 degrees C, 16.4 -95
      %RH and 10(2) -10(6) cm(-3), respectively. The main advantages of the NIM radon
      chamber with respect to maintaining a stable concentration and equilibrium factor
      of radon progenies in a wide range through automatic regulation and control of
      radon and aerosol are described. 

PMID- 25948839
TI  - Multidrug-resistant Nocardia pseudobrasiliensis presenting as multiple muscle
      abscesses.
AB  - A 79-year-old Caucasian man presented with multiple leg abscesses due to Nocardia
      pseudobrasiliensis. He was on chronic steroid therapy for myasthenia gravis. We
      present the difficulties in diagnosis and treatment of this rare organism. N.
      pseudobrasiliensis is a new emerging species that was previously thought to
      belong to the N. brasiliensis species. The distinction between the two species is
      extremely important given the different antibiotic susceptibility pattern and
      association of N. pseudobrasiliensis with more invasive and disseminated disease.

PMID- 25948840
TI  - Coma query cause.
AB  - A 54-year-old woman with coeliac disease was admitted to hospital electively for
      supplemental nutrition. Shortly after feeding started she deteriorated into a
      hyperammonemic coma with refeeding syndrome, requiring an extensive intensive
      care admission. Urea cycle disorders were investigated and a biochemical
      diagnosis of ornithine transcarbamylase deficiency was made. This is a rare
      diagnosis in the adult population. This case report summarises protein
      metabolism, urea cycle disorders and the challenges of management. 

PMID- 25948841
TI  - A SCUBA diver with acute kidney injury.
AB  - An otherwise healthy young man was transferred to our hospital after a diving
      incident. He had made an uncontrolled ascent from 10 m. On arrival he appeared
      well. No hypotensive episodes occurred during the transfer. He denied having
      arthralgias, back pain, dyspnoea or neurological symptoms. Laboratory
      investigations revealed acutely elevated creatinine (170 umol/L) and creatine
      kinase (909 U/L). Radiology was consistent with a focus of pulmonary barotrauma
      and intrinsic renal disease. Creatine kinase is a marker of arterial gas embolism
      (AGE). We determined that our patient suffered acute kidney injury as a result of
      gas embolisation to his renal vasculature from an area of pulmonary barotrauma.
      Creatinine fell the following day in response to aggressive intravenous fluids.
      This is the first reported case of acute kidney injury secondary to AGE.
      Biochemical studies should be part of the routine assessment of patients involved
      in diving incidents. 

PMID- 25948842
TI  - Follicular variant of papillary thyroid carcinoma: an unusual cause of
      thyrotoxicosis.
AB  - Thyroid carcinoma presenting as a hyperfunctioning thyroid nodule is rare. A
      further complexity is added when interpretation of the histopathology itself is
      not straightforward. We describe a case of a 16-year-old girl presenting with
      clinical and biochemical evidence of thyrotoxicosis, and a 4 cm thyroid mass. An
      ultrasound and thyroid uptake scan demonstrated a toxic adenoma. Owing to the
      nodule size, fine needle aspiration of the thyroid adenoma was performed, which
      showed findings consistent with toxic adenoma. However, in view of the size of
      the nodule, a hemithyroidectomy was performed. Histological examination of the
      thyroid revealed a follicular variant of papillary carcinoma of the thyroid, and
      the patient underwent completion thyroidectomy. We report on the case and briefly
      review the available literature relating to the diagnostic challenge of this
      presentation. 

PMID- 25948843
TI  - Extrapulmonary tuberculosis: an unusual presentation in an immunocompetent
      patient.
AB  - A 50-year-old Brazilian woman was admitted to our department because of pelvic
      pain irradiated to the lower left limb, ipsilateral ankle swelling and
      progressive weight loss. Doppler ultrasound demonstrated deep venous
      femoropopliteal thrombosis, while a thorax-abdomen CT scan showed multiple solid
      hypodense pulmonary lesions, a large hypodense lesion in the iliopsoas muscles
      bilaterally and a complex cystoid lesion at the hepatic hilum. These findings
      were better characterised as active inflammatory colliquated lymph nodes by
      positron emission tomography and echo-guided percutaneous fine-needle aspiration
      of the left iliopsoas abscessual lesion finally allowed the diagnosis of
      tubercular infection with positive cultures for Mycobacterium tuberculosis
      complex. 

PMID- 25948845
TI  - Fluoxymesterone-induced gynaecomastia in a patient with childhood aplastic
      anaemia.
AB  - Gynaecomastia is a benign condition characterised by enlargement of the male
      breast. Drug-induced gynaecomastia merits deep consideration as it may account
      for as many as 25% of all cases of gynaecomastia in adults. Although the
      mechanism is not fully clear, some mechanisms include oestrogen-like activities,
      stimulation of testicular production of oestrogens, inhibition of testosterone
      synthesis or blockade of androgen action. Anabolic steroids, in particular when
      used during the pubertal stage, may cause significant irreversible gynaecomastia.
      We report a case of 28-year-old Filipino man with persistent gynaecomastia from
      fluoxymesterone used for aplastic anaemia during his prepubertal stage. Hormonal
      work ups for gynaecomastia all turned out normal, thus isolating the drug as the
      cause. The patient was unable to undergo breast reconstruction surgery due to
      haematological contraindications, but eventually referred to psychiatry for
      counselling. This case will highlight the paradoxical effect of androgenic
      steroid used during childhood on male breast proliferation during puberty. 

PMID- 25948844
TI  - Progressive outer retinal necrosis: manifestation of human immunodeficiency virus
      infection.
AB  - We present the case of a 54-year-old man who developed progressive outer retinal
      necrosis (PORN) as an initial manifestation of HIV infection without any
      significant risk factors for infection with HIV. PORN is usually found as a
      manifestation of known AIDS late in the disease. Our patient presented with
      transient visual loss followed by decrease in visual acuity and facial rash.
      Subsequent investigation revealed anterior chamber tap positive for varicella
      zoster virus (VZV), as well as HIV positivity, with an initial CD4 count of 48
      cells/uL. Systemic and intravitreal antivirals against VZV, and highly active
      antiretroviral therapy against HIV were started, which halted further progression
      of retinal necrosis. This case highlights the importance of suspecting PORN where
      there is a rapidly progressive retinitis, and also testing the patient for HIV,
      so appropriate treatment can be started. 

PMID- 25948846
TI  - Headache in a young woman: leptomeningeal metastasis as the first presentation of
      underlying breast malignancy.
AB  - A 37-year-old woman presented with a 2-week history of persistent headache in an
      occipitotemporal distribution. The patient had experienced prior headaches and
      migraines, but this presentation was characterised by its intensity and duration.
      There was associated dizziness and blurring of vision in episodes occurring up to
      4-5 times per day. Whole body cross-sectional CT imaging and MRI of neuronal axes
      were normal. Cerebrospinal fluid cytology demonstrated large abnormal pleomorphic
      cells expressing the tumour marker CA125. Positron emission tomography
      fluorodeoxyglucose revealed bilateral axillary and cervical lymphadenopathy as
      well as increased uptake in the lateral regions of both breasts. These results
      correlated with MRI breast and mammography findings. Axillary lymph node biopsy
      showed poorly differentiated adenocarcinoma making the diagnosis of breast
      malignancy, the most likely primary site of metastatic leptomeningeal disease. In
      the 6-week interval between initial presentation and diagnosis, the patient
      deteriorated significantly with the new onset of facial nerve palsy and partial
      seizures. The treatment intent was palliative, focusing on symptom control with
      systemic chemotherapy and whole brain radiotherapy. 

PMID- 25948847
TI  - Recurrent right iliac fossa pain in patients with previous appendicectomy.
AB  - Recurrent appendicitis can occur up to 40 years after appendicectomy. A history
      of appendicectomy has often led to late diagnosis, as sepsis is attributed to
      other organs, usually the urinary tract. A case of a patient presenting with
      retained faecolith and recurrent/stump appendicitis 2 years after laparoscopic
      appendicectomy is presented. The case for having a low threshold for early CT
      scanning in patients post-appendicectomy presenting with sepsis to prevent delay
      in diagnosis is made, and this case is a useful reminder for surgeons to dissect
      as far as possible to the appendix base. The literature including important
      medicolegal cases is reviewed. 

PMID- 25948848
TI  - Pseudoseptic arthritis resulting in joint destruction.
AB  - Pseudoseptic arthritis is an increasingly recognised entity. It is an
      inflammatory arthritis that mimics septic arthritis; however, Gram stain and
      cultures are persistently negative. It is a diagnosis of exclusion. We present
      the first case, to date, in which pseudoseptic arthritis led to such severe joint
      degeneration that joint replacement surgery was required. A 54-year-old truck
      driver with rheumatoid arthritis, on immunosuppressive therapy, presented with
      acute onset severe left hip pain. He was given a clinical diagnosis of septic
      arthritis and treated with two prolonged courses of antibiotics despite
      persistently negative synovial fluid cultures. He experienced progressive joint
      destruction necessitating a two-stage total hip replacement. A retrospective
      diagnosis of pseudoseptic arthritis was made. This case demonstrates the
      difficulties inherent in differentiating between septic and pseudoseptic
      arthritis. This case also highlights the importance of accurate diagnosis and
      treatment for pseudoseptic arthritis to avoid accelerated joint destruction. 

PMID- 25948849
TI  - A pneumonia leading to blindness.

PMID- 25948850
TI  - A mitotic cause of Whipple's triad: non-islet cell tumour hypoglycaemia in
      incurable low-grade malignancy.
AB  - A 74-year-old man with known metastatic haemangiopericytoma presented with
      neuroglycopaenic symptoms of confusion and light-headedness secondary to
      recurrent episodes of fasting hypoglycaemia, which resolved with oral
      carbohydrate intake. Investigations for hypoglycaemia revealed it to be non
      insulin mediated, and subsequently due to a rare paraneoplastic phenomenon termed
      as non-islet cell tumour hypoglycaemia caused by tumoural overproduction of high
      molecular weight insulin-like growth factor-II. Despite his underlying malignancy
      being incurable, directed multimodality treatment involving regular oral
      carbohydrate intake, glucocorticoid therapy and recombinant human growth hormone
      was effective in relieving symptoms of hypoglycaemia. We discuss the importance
      of a systematic diagnostic approach to hypoglycaemia fulfilling Whipple's triad,
      as specific therapies can be invaluable to improving quality of life. 

PMID- 25948851
TI  - Ruptured distal AICA pseudoaneurysm presenting years after vestibular schwannoma
      resection and radiation.
AB  - Distal anterior inferior cerebellar artery (AICA) pseudoaneurysms are very rare
      lesions. Although cases have been previously reported, only a few have been
      reported as a result of vestibular schwannoma (VS) radiation, none have been
      reported as a result of VS resection, and only one has been reported as treated
      with parent vessel occlusion (PVO) with n-butyl cyanoacrylate (nBCA). We report a
      case of a 65-year-old man with a history of right-sided VS surgery and radiation
      who presented years later with a ruptured pseudoaneurysm of the distal right AICA
      and was treated with endovascular PVO using nBCA. The aneurysm was completely
      obliterated and the patient had no worsening of symptoms or neurological exam.
      The case illustrates a very rare complication of VS surgery and radiation as well
      as an effective treatment for distal AICA aneurysms. 

PMID- 25948852
TI  - The iatrogenic caecal polyp: can it be avoided?
AB  - A 60-year-old farmer was admitted with symptoms and signs suggestive of
      appendicitis. The diagnosis was confirmed at open appendicectomy where the
      appendix base was ligated and inverted into the caecum with a purse-string
      suture. Following an uneventful recovery and discharge, a barium enema identified
      a 2 cm filling defect in the caecal pole. A subsequent colonoscopy revealed only
      a tiny sessile polyp in the caecum with histology demonstrating normal colonic
      mucosa. This case report discusses the rare occurrence of an inverted appendix
      stump mimicking caecal pathology and the rationale of post-appendicectomy colonic
      investigation in the elderly patient. 

PMID- 25948853
TI  - Serotonin syndrome in a breast-fed neonate.
AB  - A late preterm presented with tachypnoea, jitteriness, irritability and low grade
      fever. Blood gas showed a compensated metabolic acidosis. His mother was taking
      the selective serotonin reuptake inhibitor (SSRI) fluoxetine, 60 mg/day, and he
      was exclusively breast-fed. The baby's serum level of fluoxetine on day 8 was
      within the adult therapeutic range and his symptoms were ascribed to fluoxetine
      toxicity. On changing to formula feeds, his symptoms resolved. SSRIs are commonly
      administered during pregnancy, but SSRI toxicity in infants is rarely reported.
      It is possible that this condition is under diagnosed or, alternatively,
      misdiagnosed as SSRI withdrawal in breast fed infants whose mothers are on SSRIs.
      There is limited research looking at serotonin excess in neonates, making case
      reports such as this important in our learning. Increased awareness may prompt
      more frequent measurements of blood levels in breast-fed infants whose mothers
      are on SSRIs. 

PMID- 25948854
TI  - A novel psychoactive substance poses a new challenge in the management of
      paranoid schizophrenia.
AB  - Novel psychoactive substances (NPS), or 'legal highs' are becoming more commonly
      used as recreational substances in the UK. Their clinical effects are little
      known and vary considerably between substances. This case discusses a psychiatric
      inpatient who repeatedly used a stimulant NPS called 'el blanco' while on leave,
      precipitating relapses of his schizophrenia. The patient initially denied drug
      use, considering legal highs as different from drugs. The relationship between
      NPS use and mental state was eventually revealed on careful direct questioning.
      He recovered and was discharged following treatment with clozapine and education
      about NPS use. We suggest that specific questioning about NPS usage is added to
      routine psychiatric history taking and that patients using NPS should be educated
      about the substances' use. 

PMID- 25948855
TI  - An uncommon presentation of EBV-driven HLH. Primary or secondary? An ongoing
      dilemma.
AB  - Haemophagocytic lymphohistiocytosis (HLH) is a potentially fatal syndrome, mainly
      characterised by dysregulated immune activation. The syndrome is related to a
      genetic cause, in the classic primary form, or to identified triggers such as
      infections, malignancy or rheumatological processes, in the classic secondary
      form. Epstein-Barr virus (EBV) is the most common agent implicated in hereditary
      and non-hereditary conditions. We describe a 23-month-old girl who experienced
      severe clinical deterioration with respiratory distress due a bilateral pleural
      effusion within the first week of primary EBV infection. Fever, generalised
      oedema and hepatosplenomegaly, along with a pruritic morbilliform erythematous
      rash, were the first clinical signs. Respiratory impairment followed with
      hypoxaemia and the patient was admitted to the intensive care unit for
      thoracocentesis. Further investigation showed persistent bicytopaenia,
      hypertriglyceridaemia, hyperferritinaemia and elevated alpha chain of interleukin
      2 receptor (sCD25). Diagnostic criteria for HLH were fulfilled. Therapy was
      instituted with dexamethasone, ciclosporin A and intravenous immunoglobulin 6
      days after admission with progressive clinical recovery. 

PMID- 25948856
TI  - Fenestration of the supraclinoid internal carotid artery in a patient with a
      concomitant intracranial arteriovenous malformation.
AB  - Accurately recognising a supraclinoid internal carotid artery (ICA) fenestration,
      despite its rare location, is important as it can mimic an intracranial aneurysm,
      intraluminal thrombus or focal dissection on non-invasive imaging. The
      overwhelming majority of reported supraclinoid ICA fenestrations are associated
      with intracranial aneurysms; however, a concomitant arteriovenous malformation
      (AVM) remote from the fenestration site should also be considered. We present the
      case of a 26-year-old woman with a Spetzler-Martin grade I right frontal AVM in
      whom a left supraclinoid ICA fenestration was incidentally discovered during
      cerebral angiography. She underwent n-N-Butyl Cyanoacrylate glue embolisation of
      two dominant middle cerebral artery feeders followed by neurosurgical resection.
      She tolerated procedures well without complications and has remained
      neurologically intact. 

PMID- 25948857
TI  - Neonatal lingual choristoma with thyroid hemiagenesis.
AB  - A 45-day-old infant presented with choking spells and cyanosis. Examination
      revealed a lingual cyst. Contrast-enhanced CT confirmed the diagnosis of lingual
      cyst with incidental thyroid hemiagenesis. The child underwent excision of the
      lesion, which was reported as lingual choristoma. 

PMID- 25948858
TI  - Painful ophthalmoplaegia secondary to orbital myositis.

PMID- 25948859
TI  - Acute liver injury associated with a newer formulation of the herbal weight loss
      supplement Hydroxycut.
AB  - Despite the widespread use of herbal and dietary supplements (HDS), serious cases
      of hepatotoxicity have been reported. The popular herbal weight loss supplement,
      Hydroxycut, has previously been implicated in acute liver injury. Since its
      introduction, Hydroxycut has undergone successive transformations in its
      formulation; yet, cases of liver injury have remained an ongoing problem. We
      report a case of a 41-year-old Hispanic man who developed acute hepatocellular
      liver injury with associated nausea, vomiting, jaundice, fatigue and asterixis
      attributed to the use of a newer formulation of Hydroxycut, SX-7 Clean Sensory.
      The patient required hospitalisation and improved with supportive therapy.
      Despite successive transformations in its formulation, potential liver injury
      appears to remain an ongoing problem with Hydroxycut. Our case illustrates the
      importance of obtaining a thorough medication history, including HDS, regardless
      of new or reformulated product marketing efforts. 

PMID- 25948860
TI  - An interesting case of intrathyroidal parathyroid adenoma.

PMID- 25948861
TI  - Cerebral fat emboli syndrome: do not miss the transcranial Doppler findings.

PMID- 25948862
TI  - Natural Immunity to Ebola Virus in the Syrian Hamster Requires Antibody
      Responses.
AB  - Most ebolaviruses can cause severe disease in humans and other primates, with
      high case fatality rates during human outbreaks. Although these viruses have been
      studied for almost 4 decades, little is know regarding the mechanisms by which
      they cause disease and what is important for protection or treatment after
      infection. Because of the sporadic nature of the outbreaks and difficulties
      accessing the populations affected by ebolaviruses, little is also known about
      what constitutes an appropriate immune response to infection in humans that
      survive infection. Such knowledge would allow a targeted approach to therapies.
      In contrast to humans, rodents are protected from disease on infection with
      ebolaviruses, although adapted versions of some of the viruses are lethal in
      mice, hamsters and guinea pigs. Using the recently described hamster model, along
      with T-cell depletion strategies, we show that CD4(+) T cells are required for
      natural immunity to Ebola virus infection and that CD4-dependent antibody
      responses are required for immunity in this model. 

PMID- 25948865
TI  - Deregulation of splicing factors and breast cancer development.
AB  - It is well known that many genes implicated in the development and progression of
      breast cancer undergo aberrant alternative splicing events to produce proteins
      with pro-cancer properties. These changes in alternative splicing can arise from
      mutations or single-nucleotide polymorphisms (SNPs) within the DNA sequences of
      cancer-related genes, which can strongly affect the activity of splicing factors
      and influence the splice site choice. However, it is important to note that
      absence of mutations is not sufficient to prevent misleading choices in splice
      site selection. There is now increasing evidence to demonstrate that the
      expression profile of ten splicing factors (including SRs and hnRNPs) and eight
      RNA-binding proteins changes in breast cancer cells compared with normal cells.
      These modifications strongly influence the alternative splicing pattern of many
      cancer-related genes despite the absence of any detrimental mutations within
      their DNA sequences. Thus, a comprehensive assessment of the splicing factor
      status in breast cancer is important to provide insights into the mechanisms that
      lead to breast cancer development and metastasis. Whilst most studies focus on
      mutations that affect alternative splicing in cancer-related genes, this review
      focuses on splicing factors and RNA-binding proteins that are themselves
      deregulated in breast cancer and implicated in cancer-related alternative
      splicing events. 

PMID- 25948864
TI  - Investigation of an Outbreak of Variant Influenza A(H3N2) Virus Infection
      Associated With an Agricultural Fair-Ohio, August 2012.
AB  - BACKGROUND: In 2012, one third of cases in a multistate outbreak of variant
      influenza A(H3N2) virus ([H3N2]v) infection occurred in Ohio. We conducted an
      investigation of (H3N2)v cases associated with agricultural Fair A in Ohio.
      METHODS: We surveyed Fair A swine exhibitors and their household members.
      Confirmed cases had influenza-like illness (ILI) and a positive laboratory test
      for (H3N2)v, and probable cases had ILI. We calculated attack rates. We
      determined risk factors for infection, using multivariable log-binomial
      regression. RESULTS: We identified 20 confirmed and 94 probable cases associated
      with Fair A. Among 114 cases, the median age was 10 years, there were no
      hospitalizations or deaths, and 82% had swine exposure. In the exhibitor
      household cohort of 359 persons (83 households), we identified 6 confirmed cases
      (2%) and 40 probable cases (11%). An age of <10 years was a significant risk
      factor (P < .01) for illness. One instance of likely human-to-human transmission
      was identified. CONCLUSIONS: In this (H3N2)v outbreak, no evidence of sustained
      human-to-human (H3N2)v transmission was found. Our risk factor analysis
      contributed to the development of the recommendation that people at increased
      risk of influenza-associated complications, including children aged <5 years,
      avoid swine barns at fairs during the 2012 fair season.

PMID- 25948863
TI  - Changes in Bone Mineral Density After Initiation of Antiretroviral Treatment With
      Tenofovir Disoproxil Fumarate/Emtricitabine Plus Atazanavir/Ritonavir,
      Darunavir/Ritonavir, or Raltegravir.
AB  - BACKGROUND: Specific antiretroviral therapy (ART) medications and the severity of
      human immunodeficiency virus (HIV) disease before treatment contribute to bone
      mineral density (BMD) loss after ART initiation. METHODS: We compared the
      percentage change in BMD over 96 weeks in 328 HIV-infected, treatment-naive
      individuals randomized equally to tenofovir disoproxil fumarate/emtricitabine
      (TDF/FTC) plus atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or
      raltegravir (RAL). We also determined whether baseline levels of inflammation
      markers and immune activation were independently associated with BMD loss.
      RESULTS: At week 96, the mean percentage changes from baseline in spine and hip
      BMDs were similar in the protease inhibitor (PI) arms (spine: -4.0% in the ATV/r
      group vs -3.6% in the DRV/r [P = .42]; hip: -3.9% in the ATV/r group vs -3.4% in
      the DRV/r group [P = .36]) but were greater in the combined PI arms than in the
      RAL arm (spine: -3.8% vs -1.8% [P < .001]; hip: -3.7% vs -2.4% [P = .005]). In
      multivariable analyses, higher baseline concentrations of high-sensitivity C
      reactive protein, interleukin 6, and soluble CD14 were associated with greater
      total hip BMD loss, whereas markers of CD4(+) T-cell senescence and exhaustion
      (CD4(+)CD28(-)CD57(+)PD1(+)) and CD4(+) T-cell activation (CD4(+)CD38(+)HLA
      DR(+)) were associated with lumbar spine BMD loss. CONCLUSIONS: BMD losses 96
      weeks after ART initiation were similar in magnitude among patients receiving
      PIs, ATV/r, or DRV/r but lowest among those receiving RAL. Inflammation and
      immune activation/senescence before ART initiation independently predicted
      subsequent BMD loss.

PMID- 25948866
TI  - Decoding tactile afferent activity to obtain an estimate of instantaneous force
      and torque applied to the fingerpad.
AB  - Dexterous manipulation is not possible without sensory information about object
      properties and manipulative forces. Fundamental neuroscience has been unable to
      demonstrate how information about multiple stimulus parameters may be
      continuously extracted, concurrently, from a population of tactile afferents.
      This is the first study to demonstrate this, using spike trains recorded from
      tactile afferents innervating the monkey fingerpad. A multiple-regression model,
      requiring no a priori knowledge of stimulus-onset times or stimulus combination,
      was developed to obtain continuous estimates of instantaneous force and torque.
      The stimuli consisted of a normal-force ramp (to a plateau of 1.8, 2.2, or 2.5
      N), on top of which -3.5, -2.0, 0, +2.0, or +3.5 mNm torque was applied about the
      normal to the skin surface. The model inputs were sliding windows of binned spike
      counts recorded from each afferent. Models were trained and tested by 15-fold
      cross-validation to estimate instantaneous normal force and torque over the
      entire stimulation period. With the use of the spike trains from 58 slow-adapting
      type I and 25 fast-adapting type I afferents, the instantaneous normal force and
      torque could be estimated with small error. This study demonstrated that
      instantaneous force and torque parameters could be reliably extracted from a
      small number of tactile afferent responses in a real-time fashion with stimulus
      combinations that the model had not been exposed to during training. Analysis of
      the model weights may reveal how interactions between stimulus parameters could
      be disentangled for complex population responses and could be used to test
      neurophysiologically relevant hypotheses about encoding mechanisms. 

PMID- 25948867
TI  - Dynamics of the functional link between area MT LFPs and motion detection.
AB  - The evolution of a visually guided perceptual decision results from multiple
      neural processes, and recent work suggests that signals with different neural
      origins are reflected in separate frequency bands of the cortical local field
      potential (LFP). Spike activity and LFPs in the middle temporal area (MT) have a
      functional link with the perception of motion stimuli (referred to as neural
      behavioral correlation). To cast light on the different neural origins that
      underlie this functional link, we compared the temporal dynamics of the neural
      behavioral correlations of MT spikes and LFPs. Wide-band activity was
      simultaneously recorded from two locations of MT from monkeys performing a
      threshold, two-stimuli, motion pulse detection task. Shortly after the motion
      pulse occurred, we found that high-gamma (100-200 Hz) LFPs had a fast, positive
      correlation with detection performance that was similar to that of the spike
      response. Beta (10-30 Hz) LFPs were negatively correlated with detection
      performance, but their dynamics were much slower, peaked late, and did not depend
      on stimulus configuration or reaction time. A late change in the correlation of
      all LFPs across the two recording electrodes suggests that a common input arrived
      at both MT locations prior to the behavioral response. Our results support a
      framework in which early high-gamma LFPs likely reflected fast, bottom-up,
      sensory processing that was causally linked to perception of the motion pulse. In
      comparison, late-arriving beta and high-gamma LFPs likely reflected slower, top
      down, sources of neural-behavioral correlation that originated after the
      perception of the motion pulse. 

PMID- 25948868
TI  - Specific electrophysiological components disentangle affective sharing and
      empathic concern in psychopathy.
AB  - Empathic impairment is one of the hallmarks of psychopathy, a personality
      dimension associated with poverty in affective reactions, lack of attachment to
      others, and a callous disregard for the feelings, rights, and welfare of others.
      Neuroscience research on the relation between empathy and psychopathy has
      predominately focused on the affective sharing and cognitive components of
      empathy in forensic populations, and much less on empathic concern. The current
      study used high-density electroencephalography in a community sample to examine
      the spatiotemporal neurodynamic responses when viewing people in physical
      distress under two subjective contexts: one evoking affective sharing, the other,
      empathic concern. Results indicate that early automatic (175-275 ms) and later
      controlled responses (LPP 400-1,000 ms) were differentially modulated by
      engagement in affective sharing or empathic concern. Importantly, the late event
      related potentials (ERP) component was significantly impacted by dispositional
      empathy and psychopathy, but the early component was not. Individual differences
      in dispositional empathic concern directly predicted gamma coherence (25-40 Hz),
      whereas psychopathy was inversely modulatory. Interestingly, significant
      suppression in the mu/alpha band (8-13 Hz) when perceiving others in distress was
      positively associated with higher trait psychopathy, which argues against the
      assumption that sensorimotor resonance underpins empathy. Greater scores on trait
      psychopathy were inversely related to subjective ratings of both empathic concern
      and affective sharing. Overall, the study demonstrates that neural markers of
      affective sharing and empathic concern to the same cues of another's distress can
      be distinguished at an electrophysiological level, and that psychopathy alters
      later time-locked differentiations and spectral coherence associated with
      empathic concern. 

PMID- 25948869
TI  - Effort, success, and nonuse determine arm choice.
AB  - How do humans choose one arm or the other to reach single targets in front of the
      body? Current theories of reward-driven decisionmaking predict that choice
      results from a comparison of "action values," which are the expected rewards for
      possible actions in a given state. In addition, current theories of motor control
      predict that in planning arm movements, humans minimize an expected motor cost
      that balances motor effort and endpoint accuracy. Here, we test the hypotheses
      that arm choice is determined by comparison of action values comprising expected
      effort and expected task success for each arm, as well as a handedness bias.
      Right-handed subjects, in either a large or small target condition, were first
      instructed to use each hand in turn to shoot through an array of targets and then
      to choose either hand to shoot through the same targets. Effort was estimated via
      inverse kinematics and dynamics. A mixed-effects logistic-regression analysis
      showed that, as predicted, both expected effort and expected success predicted
      choice, as did arm use in the preceding trial. Finally, individual parameter
      estimation showed that the handedness bias correlated with mean difference
      between right- and left-arm success, leading to overall lower use of the left
      arm. We discuss our results in light of arm nonuse in individuals' poststroke. 

PMID- 25948870
TI  - Confidence estimation as a stochastic process in a neurodynamical system of
      decision making.
AB  - Evaluation of confidence about one's knowledge is key to the brain's ability to
      monitor cognition. To investigate the neural mechanism of confidence assessment,
      we examined a biologically realistic spiking network model and found that it
      reproduced salient behavioral observations and single-neuron activity data from a
      monkey experiment designed to study confidence about a decision under
      uncertainty. Interestingly, the model predicts that changes of mind can occur in
      a mnemonic delay when confidence is low; the probability of changes of mind
      increases (decreases) with task difficulty in correct (error) trials.
      Furthermore, a so-called "hard-easy effect" observed in humans naturally emerges,
      i.e., behavior shows underconfidence (underestimation of correct rate) for easy
      or moderately difficult tasks and overconfidence (overestimation of correct rate)
      for very difficult tasks. Importantly, in the model, confidence is computed using
      a simple neural signal in individual trials, without explicit representation of
      probability functions. Therefore, even a concept of metacognition can be
      explained by sampling a stochastic neural activity pattern. 

PMID- 25948871
TI  - Self-regulation of adult thalamocortical neurons.
AB  - The thalamus acts as a conduit for sensory and other information traveling to the
      cortex. In response to continuous sensory stimulation in vivo, the firing rate of
      thalamocortical neurons initially increases, but then within a minute firing rate
      decreases and T-type Ca(2+) channel-dependent action potential burst firing
      emerges. While neuromodulatory systems could play a role in this inhibitory
      response, we instead report a novel and cell-autonomous inhibitory mechanism
      intrinsic to the thalamic relay neuron. Direct intracellular stimulation of
      thalamocortical neuron firing initially triggered a continuous and high rate of
      action potential discharge, but within a minute membrane potential (Vm) was
      hyperpolarized and firing rate to the same stimulus was decreased. This self
      inhibition was observed across a wide variety of thalamic nuclei, and in a subset
      firing mode switched from tonic to bursting. The self-inhibition resisted
      blockers of intracellular Ca(2+) signaling, Na(+)-K(+)-ATPases, and G protein
      regulated inward rectifier (GIRK) channels as implicated in other neuron
      subtypes, but instead was in part inhibited by an ATP-sensitive K(+) channel
      blocker. The results identify a new homeostatic mechanism within the thalamus
      capable of gating excitatory signals at the single-cell level. 

PMID- 25948873
TI  - Urinary C-X-C Motif Chemokine 10 Independently Improves the Noninvasive Diagnosis
      of Antibody-Mediated Kidney Allograft Rejection.
AB  - Urinary levels of C-X-C motif chemokine 9 (CXCL9) and CXCL10 can noninvasively
      diagnose T cell-mediated rejection (TCMR) of renal allografts. However,
      performance of these molecules as diagnostic/prognostic markers of antibody
      mediated rejection (ABMR) is unknown. We investigated urinary CXCL9 and CXCL10
      levels in a highly sensitized cohort of 244 renal allograft recipients (67 with
      preformed donor-specific antibodies [DSAs]) with 281 indication biopsy samples.
      We assessed the benefit of adding these biomarkers to conventional models for
      diagnosing/prognosing ABMR. Urinary CXCL9 and CXCL10 levels, normalized to urine
      creatinine (Cr) levels (CXCL9:Cr and CXCL10:Cr) or not, correlated with the
      extent of tubulointerstitial (i+t score; all P<0.001) and microvascular (g+ptc
      score; all P<0.001) inflammation. CXCL10:Cr diagnosed TCMR (area under the curve
      [AUC]=0.80; 95% confidence interval [95% CI], 0.68 to 0.92; P<0.001) and ABMR
      (AUC=0.76; 95% CI, 0.69 to 0.82; P<0.001) with high accuracy, even in the absence
      of tubulointerstitial inflammation (AUC=0.70; 95% CI, 0.61 to 0.79; P<0.001).
      Although mean fluorescence intensity of the immunodominant DSA diagnosed ABMR
      (AUC=0.75; 95% CI, 0.68 to 0.82; P<0.001), combining urinary CXCL10:Cr with
      immunodominant DSA levels improved the diagnosis of ABMR (AUC=0.83; 95% CI, 0.77
      to 0.89; P<0.001). At the time of ABMR, urinary CXCL10:Cr ratio was independently
      associated with an increased risk of graft loss. In conclusion, urinary CXCL10:Cr
      ratio associates with tubulointerstitial and microvascular inflammation of the
      renal allograft. Combining the urinary CXCL10:Cr ratio with DSA monitoring
      significantly improves the noninvasive diagnosis of ABMR and the stratification
      of patients at high risk for graft loss. 

PMID- 25948872
TI  - Benefits and harms of mammography screening after age 74 years: model estimates
      of overdiagnosis.
AB  - BACKGROUND: The aim of this study was to quantify the benefits and harms of
      mammography screening after age 74 years, focusing on the amount of overdiagnosis
      of invasive breast cancer and ductal carcinoma in situ (DCIS). METHODS: Three
      well-established microsimulation models were used to simulate a cohort of
      American women born in 1960. All women received biennial screening starting at
      age 50 years with cessation ages varying from 74 up to 96 years. We estimated the
      number of life-years gained (LYG), quality-adjusted life-years, breast cancer
      deaths averted, false-positives, and overdiagnosed women per 1000 screens.
      RESULTS: The models predicted that there were 7.8 to 11.4 LYG per 1000 screens at
      age 74 years (range across models), decreasing to 4.8 to 7.8 LYG per 1000 screens
      at age 80 years, and 1.4 to 2.4 LYG per 1000 screens at age 90 years. When
      adjusted for quality-of-life decrements, the LYG decreased by 5% to 13% at age 74
      years and 11% to 22% at age 80 years. At age 90 to 92 years, all LYG were
      counterbalanced by a loss in quality-of-life, mainly because of the increasing
      number of overdiagnosed breast cancers per 1000 screens: 1.2 to 5.0 at age 74
      years, 1.8 to 6.0 at age 80 years, and 3.7 to 7.5 at age 90 years. The age at
      which harms began to outweigh benefits shifted to a younger age when larger or
      longer utility losses because of a breast cancer diagnosis were assumed.
      CONCLUSION: The balance between screening benefits and harms becomes less
      favorable after age 74 years. At age 90 years, harms outweigh benefits, largely
      as a consequence of overdiagnosis. This age was the same across the three models,
      despite important model differences in assumptions on DCIS.

PMID- 25948875
TI  - Enhanced social learning between siblings in common ravens, Corvus corax.
AB  - It has been suggested that social dynamics affect social learning but empirical
      support for this idea is scarce. Here we show that affiliate relationships among
      kin indeed enhance the performance of common ravens, Corvus corax, in a social
      learning task. Via daily behavioural protocols we first monitored social dynamics
      in our group of captive young ravens. Siblings spent significantly more time in
      close proximity to each other than did nonsiblings. We subsequently tested birds
      on a stimulus enhancement task in model-observer dyads composed of both siblings
      and nonsiblings. During demonstration the observer could watch the model
      manipulating one particular object (target object) in an adjacent room. After
      removing the model, the observer was confronted with five different objects
      including the former target object. Observers from sibling dyads handled the
      target object for significantly longer periods of time as compared with the other
      four available objects, whereas observers from nonsibling dyads did not show a
      preference for the target object. Also, siblings matched the model's decision to
      cache or not to cache objects significantly more often than did nonsiblings.
      Hence, siblings were likely to attend to both, the behaviour of the model
      (caching or noncaching) and object-specific details. Our results support the
      hypothesis that affiliate relations between individuals affect the transmission
      of information and may lead to directed social learning even when spatial
      proximity has been experimentally controlled for.

PMID- 25948874
TI  - Urine CXCL10/IP-10 Fingers Ongoing Antibody-Mediated Kidney Graft Rejection.

PMID- 25948876
TI  - SAME-SEX PARTNERSHIPS AND THE HEALTH OF OLDER ADULTS.
AB  - While extensive research has examined associations between marriage,
      cohabitation, and the health of heterosexual adults, it remains unclear whether
      similar patterns of health are associated with same-sex partnerships for lesbian,
      gay, and bisexual (LGB) older adults. This article examines whether having a same
      sex partner is associated with general self-reported health and depressive
      symptoms for LGB older adults. Based on survey data collected from LGB adults 50
      years of age and older, having a same-sex partner was associated with better self
      reported health and fewer depressive symptoms when compared with single LGB older
      adults, controlling for gender, age, education, income, sexuality, and
      relationship duration. Relationship duration did not significantly impact the
      association between partnership status and health. In light of recent public
      debates and changes in policies regarding same-sex partnerships, more socially
      integrated relationship statuses appear to play a role in better health for LGB
      older adults.

PMID- 25948878
TI  - IPUMS-International: Integrating and Disseminating High Precision Population
      Census Samples of the USA, Greece, Europe and the World.

PMID- 25948877
TI  - The performance of ravens on simple discrimination tasks: a preliminary study.
AB  - Recent studies suggest the existence of primate-like cognitive abilities in
      corvids. Although the learning abilities of corvids in comparison to other
      species have been investigated before, little is known on how corvids perform on
      simple discrimination tasks if tested in experimental settings comparable to
      those that have been used for studying complex cognitive abilities. In this
      study, we tested a captive group of 12 ravens (Corvus corax) on four
      discrimination problems and their reversals. In contrast to other studies
      investigating learning abilities, our ravens were not food deprived and
      participation in experiments was voluntary. This preliminary study showed that
      all ravens successfully solved feature and position discriminations and several
      of the ravens could solve new tasks in a few trials, making very few mistakes.

PMID- 25948880
TI  - Enhanced levels of chemokines and their receptors in the colon of microscopic
      colitis patients indicate mixed immune cell recruitment.
AB  - Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic
      colitis (LC), is a common cause of chronic diarrhea. Various immune cell
      infiltrations in the epithelium and lamina propria are seen in MC
      immunopathology. We compared gene and protein expressions of different immune
      cell attracting chemokines and their receptors in colon biopsies from MC patients
      in active disease or histopathological remission (CC/LC-HR) with controls, using
      qRT-PCR and Luminex, respectively. CC and LC patients with active disease
      demonstrated a mixed chemokine profile with significantly enhanced gene and/or
      protein expressions of the chemokines CCL2, CCL3, CCL4, CCL5, CCL7, CCL22, CXCL8,
      CXCL9, CXCL10, CXCL11, and CX3CL1 and the receptors CCR2, CCR3, CCR4, CXCR1,
      CXCR2, and CX3CR1. Enhanced chemokine/chemokine receptor gene and protein levels
      in LC-HR patients were similar to LC patients, whereas CC-HR patients
      demonstrated almost normalized levels. These findings expand the current
      understanding of the involvement of various immune cells in MC immunopathology
      and endorse chemokines as potential diagnostic markers as well as therapeutic
      candidates. Moreover, this study further supports the hypothesis that CC and LC
      are two different entities due to differences in their immunoregulatory
      responses. 

PMID- 25948879
TI  - Long-term neuropsychological sequelae in HIV-seronegative cryptococcal
      meningoencephalitis patients with and without ventriculoperitoneal shunts: a cine
      MRI study.
AB  - BACKGROUND: Hydrocephalus in cryptococcal meningoencephalitis is most commonly
      managed with a ventriculoperitoneal shunt. This study applied cine magnetic
      resonance imaging (MRI) to evaluate initial disease severity on long-term
      cerebrospinal fluid (CSF) flow dynamics and associated neuropsychological
      sequelae in cryptococcal meningoencephalitis patients with and without
      ventriculoperitoneal shunts. METHODS: Eighteen human immunodeficiency virus
      seronegative cryptococcal meningoencephalitis patients (10 with shunts versus 8
      without shunts) were compared with 32 age- and sex-matched healthy volunteers.
      All subjects underwent complete neurologic examination and neuropsychological
      testing. Cine MRI was conducted to evaluate CSF flow parameters. Initial CSF
      laboratory analysis and imaging findings were correlated with present CSF flow
      parameters and neuropsychological scores. RESULTS: Patients without shunts had
      higher average flow than controls, suggesting chronic hydrocephalus. Initial
      Evans ratios and CSF glucose levels were associated with CSF peak velocity and
      flow. Worsening CSF flow parameters correlated with decreased neuropsychological
      performance. CONCLUSIONS: CSF flow parameter differences between the cryptococcal
      meningoencephalitis patients both with and without ventriculoperitoneal shunts
      could be detected by cine MRI and correlated with acute stage disease severity
      and chronic stage neuropsychological results. Cine MRI is useful for assessing
      the chronic hydrocephalus that may lead to neuropsychological deficits in
      cryptococcal meningoencephalitis patients.

PMID- 25948881
TI  - Innate immunity components and cytokines in gastric mucosa in children with
      Helicobacter pylori infection.
AB  - PURPOSE. To investigate the expression of innate immunity components and
      cytokines in the gastric mucosa among H. pylori infected and uninfected children.
      Materials and Methods. Biopsies of the antral gastric mucosa from children with
      dyspeptic symptoms were evaluated. Gene expressions of innate immunity receptors
      and cytokines were measured by quantitative real-time PCR. The protein expression
      of selected molecules was tested by immunohistochemistry. RESULTS. H. pylori
      infection did not lead to a significant upregulation of MyD88, TLR2, TLR4, CD14,
      TREM1, and TREM2 mRNA expression but instead resulted in high mRNA expression of
      IL-6, IL-10, IFN-gamma, TNF-alpha, and CD163. H. pylori cagA(+) infection was
      associated with higher IL-6 and IL-10 mRNA expression, as compared to cagA(-)
      strains. H. pylori infected children showed increased IFN-gamma and TNF-alpha
      protein levels. IFN-gamma mRNA expression correlated with both H. pylori density
      of colonization and lymphocytic infiltration in the gastric mucosa, whereas TNF
      alpha protein expression correlated with bacterial density. CONCLUSION. H. pylori
      infection in children was characterized by (a) Th1 expression profile, (b) lack
      of mRNA overexpression of natural immunity receptors, and (c) strong anti
      inflammatory activities in the gastric mucosa, possibly resulting from increased
      activity of anti-inflammatory M2 macrophages. This may explain the mildly
      inflammatory gastric inflammation often observed among H. pylori infected
      children.

PMID- 25948882
TI  - Transcriptional regulators of claudins in epithelial tight junctions.
AB  - Human gastrointestinal tract is covered by a monolayer of specialized epithelial
      cells that constitute a protective barrier surface to external toxic and
      infectious agents along with metabolic and digestive functions. Intercellular
      junctions, among epithelial cells, such as desmosomes, adherens, gap, and tight
      junctions (TJs), not only provide mechanical integrity but also limit movement of
      molecules across the monolayer. TJ is a complex structure composed of
      approximately 35 different proteins that interact with each other at the apical
      side of two adjacent epithelial cells. Claudin family proteins are important
      members of TJ with so far 24 known isoforms in different species. Claudins are
      structural proteins of TJ that help to control the paracellular movement by
      forming fence and barrier across the epithelial monolayer. Altered function of
      claudins is implicated in different form of cancers, inflammatory bowel diseases
      (IBDs), and leaky diarrhea. Based on their significant role in the molecular
      architecture of TJ, diversity, and disease association, further understanding
      about claudin family proteins and their genetic/epigenetic regulators is
      indispensable. 

PMID- 25948883
TI  - Claudin-4 undergoes age-dependent change in cellular localization on pig jejunal
      villous epithelial cells, independent of bacterial colonization.
AB  - Newborn piglets are immunologically naive and must receive passive immunity via
      colostrum within 24 hours to survive. Mechanisms by which the newborn piglet gut
      facilitates uptake of colostral cells, antibodies, and proteins may include FcRn
      and pIgR receptor-mediated endocytosis and paracellular transport between tight
      junctions (TJs). In the present study, FcRn gene (FCGRT) was minimally expressed
      in 6-week-old gut and newborn jejunum but it was expressed at significantly
      higher levels in the ileum of newborn piglets. pIgR was highly expressed in the
      jejunum and ileum of 6-week-old animals but only minimally in neonatal gut.
      Immunohistochemical analysis showed that Claudin-5 localized to blood vessel
      endothelial cells. Claudin-4 was strongly localized to the apical aspect of
      jejunal epithelial cells for the first 2 days of life after which it was
      redistributed to the lateral surface between adjacent enterocytes. Claudin-4 was
      localized to ileal lateral surfaces within 24 hours after birth indicating
      regional and temporal differences. Tissue from gnotobiotic piglets showed that
      commensal microbiota did not influence Claudin-4 surface localization on jejunal
      or ileal enterocytes. Regulation of TJs by Claudin-4 surface localization
      requires further investigation. Understanding the factors that regulate gut
      barrier maturation may yield protective strategies against infectious diseases. 

PMID- 25948884
TI  - Enterococcus faecium NCIMB 10415 modulates epithelial integrity, heat shock
      protein, and proinflammatory cytokine response in intestinal cells.
AB  - Probiotics have shown positive effects on gastrointestinal diseases; they have
      barrier-modulating effects and change the inflammatory response towards pathogens
      in studies in vitro. The aim of this investigation has been to examine the
      response of intestinal epithelial cells to Enterococcus faecium NCIMB 10415 (E.
      faecium), a probiotic positively affecting diarrhea incidence in piglets, and two
      pathogenic Escherichia coli (E. coli) strains, with specific focus on the
      probiotic modulation of the response to the pathogenic challenge. Porcine (IPEC
      J2) and human (Caco-2) intestinal cells were incubated without bacteria
      (control), with E. faecium, with enteropathogenic (EPEC) or enterotoxigenic E.
      coli (ETEC) each alone or in combination with E. faecium. The ETEC strain
      decreased transepithelial resistance (TER) and increased IL-8 mRNA and protein
      expression in both cell lines compared with control cells, an effect that could
      be prevented by pre- and coincubation with E. faecium. Similar effects were
      observed for the increased expression of heat shock protein 70 in Caco-2 cells.
      When the cells were challenged by the EPEC strain, no such pattern of changes
      could be observed. The reduced decrease in TER and the reduction of the
      proinflammatory and stress response of enterocytes following pathogenic challenge
      indicate the protective effect of the probiotic. 

PMID- 25948885
TI  - Sterile inflammation in Drosophila.
AB  - The study of immune responses in Drosophila has already yielded significant
      results with impacts on our understanding of vertebrate immunity, such as the
      characterization of the Toll receptor. Several recent papers have focused on the
      humoral response to damage signals rather than pathogens, particularly damage
      signals from tumour-like tissues generated by loss of cell polarity or
      chromosomal instability. Both the triggers that generate this sterile
      inflammation and the systemic and local effects of it are only just beginning to
      be characterized in Drosophila. Here we review the molecular mechanisms that are
      known that give rise to the recruitment of Drosophila phagocytes, called
      hemocytes, as well as the signals, such as TNFalpha, that stimulated hemocytes
      emit at sites of perceived damage. The signalling consequences of inflammation,
      such as the activation of JNK, and the potential for modifying this response are
      also discussed. 

PMID- 25948886
TI  - Value of caffeic acid phenethyl ester pretreatment in experimental sepsis model
      in rats.
AB  - BACKGROUND AND AIM: The aim of this study was to determine the actions of caffeic
      acid phenethyl ester (CAPE) on the changes of endothelin-1 (ET-1) level, tumor
      necrosis factor- (TNF-) alpha, and oxidative stress parameters such as superoxide
      dismutase (SOD) activities and malondialdehyde (MDA) levels in experimental
      sepsis model in rats. MATERIALS AND METHODS: Twenty-four rats were randomly
      divided into three experimental groups: sham (group 1), sepsis (group 2), and
      sepsis + CAPE (group 3), n = 8 each. CAPE was administered (10 umol/kg)
      intraperitoneally to group 3 before sepsis induction. Serum ET-1, serum TNF
      alpha, tissue SOD activity, and tissue MDA levels were measured in all groups.
      RESULTS: Pretreatment with CAPE decreased ET-1, TNF-alpha, and MDA levels in
      sepsis induced rats. Additionally SOD activities were higher in rats pretreated
      with CAPE after sepsis induction. CONCLUSION: Our results demonstrate that CAPE
      may have a beneficial effect on ET and TNF-alpha levels and oxidative stress
      parameters induced by sepsis in experimental rat models. Therefore treatment with
      CAPE can be used to avoid devastating effects of sepsis.

PMID- 25948888
TI  - Indian guidelines for asthma: Adherence is the key.

PMID- 25948887
TI  - Matrix metalloproteinases in inflammatory bowel disease: an update.
AB  - Matrix metalloproteinases (MMPs) are known to be upregulated in inflammatory
      bowel disease (IBD) and other inflammatory conditions, but while their
      involvement is clear, their role in many settings has yet to be determined.
      Studies of the involvement of MMPs in IBD since 2006 have revealed an array of
      immune and stromal cells which release the proteases in response to inflammatory
      cytokines and growth factors. Through digestion of the extracellular matrix and
      cleavage of bioactive proteins, a huge diversity of roles have been revealed for
      the MMPs in IBD, where they have been shown to regulate epithelial barrier
      function, immune response, angiogenesis, fibrosis, and wound healing. For this
      reason, MMPs have been recognised as potential biomarkers for disease activity in
      IBD and inhibition remains a huge area of interest. This review describes new
      roles of MMPs in the pathophysiology of IBD and suggests future directions for
      the development of treatment strategies in this condition. 

PMID- 25948890
TI  - Chlorhexidine: Hypersensitivity and anaphylactic reactions in the perioperative
      setting.

PMID- 25948891
TI  - Animal testing in the history of anesthesia: Now and then, some stories, some
      facts.

PMID- 25948892
TI  - Perioperative chlorhexidine allergy: Is it serious?
AB  - Chlorhexidine is an antiseptic agent, commonly used, in many different
      preparations, and for multiple purposes. Despite its superior antimicrobial
      properties, chlorhexidine is a potentially allergenic substance. The following is
      a review of the current evidence-based knowledge of allergic reactions to
      chlorhexidine associated with surgical and interventional procedures. 

PMID- 25948893
TI  - Interdisciplinary position statement on management of hyperglycemia in peri
      operative and intensive care.
AB  - Hospitalized patients with diabetes pose numerous clinical challenges, including
      hyperglycemia, which may often be difficult to control. The therapeutic
      challenges are further accentuated by the difficulty in practical application of
      existing guidelines among Indian and South Asian patients. The present review
      highlights the various clinical challenges encountered during management of
      different diabetic hospitalized populations, and attempts to collate a set of
      practical, patient and physician friendly recommendations to manage hyperglycemia
      in such patients. 

PMID- 25948894
TI  - Comparison of margin of safety following two different techniques of
      preoxygenation.
AB  - BACKGROUND AND AIMS: Shortening the duration of efficacious preoxygenation would
      provide benefit in emergency situations like fetal distress etc. This study aims
      to compare the margin of safety following preoxygenation using 8 vital capacity
      breaths (VCB) in 1 min and tidal volume breathing (TVB) for 3 min, by assessing
      changes in PaO2 and apnea induced desaturation time. MATERIAL AND METHODS:
      Patients were randomly divided into Group A and B. In Group A, 3 min of TVB using
      O2 flow of 5 l/min and in Group B, 8 VCB in 60 s using O2 flow of 10 l/min were
      used. Anesthesia was induced in all patients with propofol followed by
      succinylcholine 2 mg/kg intravenously. Mask ventilation was not done and
      following intubation endotracheal tube was kept open to atmosphere. The time
      taken for the patients to desaturate to 90% was noted and immediately ventilation
      was resumed. Arterial blood gas samples were taken while patients were breathing
      room air, immediately after preoxygenation and at 90% desaturation. RESULTS:
      Baseline PaO2 of both the groups were comparable. After preoxygenation Group B
      had a significantly high PaO2 value than Group A (439.05 +/- 62.20 vs. 345.16 +/-
      20.80). At 90% desaturation there was no significant difference between groups.
      Group B showed a significantly high apnea induced desaturation time when compared
      to Group A (6.87 +/- 1.78 vs. 3.47 +/- 0.38 min). CONCLUSIONS: Preoxygenation by
      8 VCB in 1 min provides a greater margin of safety, as it results in a
      significantly high PaO2 with an almost doubled apnea induced desaturation time,
      in comparison with TVB for 3 min.

PMID- 25948895
TI  - Role of flupirtine as a preemptive analgesic in patients undergoing laparoscopic
      cholecystectomy.
AB  - BACKGROUND AND AIMS: Postsurgical pain is the leading complaint after
      laparoscopic cholecystectomy that may delay the postoperative recovery and hence
      we undertook a prospective randomized trial to analyze the role of flupirtine as
      a preemptive analgesic for postoperative pain relief in patients undergoing above
      surgery. MATERIAL AND METHODS: A total of 66 cases were randomly assigned to two
      groups to receive capsule flupirtine (200 mg) or capsule vitamin B complex
      administered orally, 2 h before the laparoscopic cholecystectomy surgery. Time to
      first analgesic requirement, assessment of postoperative pain in terms of visual
      analog score, and analgesic requirement postoperatively were measured as a
      primary outcome. RESULTS: Time to first analgesic requirement was significantly
      prolonged in the flupirtine group as compared with the placebo group. There was
      significant pain reduction in early postoperative period (up to 4 h), but no
      changes occurred thereafter. Total analgesic requirement (including rescue
      analgesia) and side-effects were comparable between the groups except for higher
      sedation in flupirtine group. CONCLUSIONS: Flupirtine is effective as a
      preemptive analgesic in providing adequate pain relief during the immediate
      postoperative period after laparoscopic cholecystectomy surgery. However,
      continuation of drug therapy postoperatively could possibly delineate its optimal
      analgesic profile more profoundly.

PMID- 25948896
TI  - Influence of hemodynamics and intra-operative hydration on biochemical outcome of
      renal transplant recipients.
AB  - BACKGROUND AND AIMS: Early graft function is crucial for successful kidney
      transplantation. The aim of our study was to evaluate the effect of intra
      operative central venous pressure (CVP) and mean arterial pressure (MAP) on early
      graft function and biochemical outcome. MATERIAL AND METHODS: This was a
      retrospective study carried out on patients undergoing renal transplant only from
      live-related donors between March 2011 and May 2013. We mainly divided the
      patients into two groups based on CVP and mean MAP. One group had CVP more than
      12 and other with CVP <12 mmHg at the time of declamping. Further one group was
      with mean MAP >100 mmHg and other with mean MAP of <100 mmHg. The graft outcome
      of genetically related and genetically unrelated donors was also evaluated in
      early postoperative period. The trend in fall of serum creatinine was studied
      during the first five post-operative days. The effect of age, dry weight, sex,
      relation with donor and intraoperative factors like MAP and CVP on early graft
      function were analysed. Correlation analysis, analysis of variance test (ANOVA)
      and multivariate analysis technique were used in this study for statistical
      computation. RESULTS: The mean CVP at the time of declamping was 13.91 mmHg. The
      minimum CVP was 6 mmHg in one patient who had ischemic heart disease with low
      ejection fraction. All 5 days mean serum creatinine values were comparable in two
      groups on 1(st), 2(nd), 3(rd) and 4(th) postoperative days. The mean MAP at the
      time of declamping was 111.22 mmHg. Mean MAP varied from a minimum of 95 mmHg to
      maximum of 131 mmHg. There was no significant difference in two groups on 1(st),
      2(nd), 3(rd), 4(th) and 5(th) postoperative days. CONCLUSION: A CVP around 12
      mmHg and mean MAP >95 mmHg with good perioperative fluid hydration is associated
      with good early graft function.

PMID- 25948897
TI  - Comparison of hemodynamic effects of intravenous etomidate versus propofol during
      induction and intubation using entropy guided hypnosis levels.
AB  - BACKGROUND AND AIMS: This study aimed to compare the hemodynamic responses during
      induction and intubation between propofol and etomidate using entropy guided
      hypnosis. MATERIAL AND METHODS: Sixty ASA I & II patients in the age group 20-60
      yrs, scheduled for modified radical mastectomy were randomly allocated in two
      groups based on induction agent Etomidate or Propofol. Both groups received
      intravenous midazolam 0.03 mg kg(-1) and fentanyl 2 MUg kg(-1) as premedication.
      After induction with the desired agent titrated to entropy 40, vecuronium 0.1 mg
      kg(-1) was administered for neuromuscular blockade. Heart rate, systolic,
      diastolic and mean arterial pressures, response entropy [RE] and state entropy
      [SE] were recorded at baseline, induction and upto three minutes post intubation.
      Data was subject to statistical analysis SPSS (version 12.0) the paired and the
      unpaired Student's T-tests for equality of means. RESULTS: Etomidate provided
      hemodynamic stability without the requirement of any rescue drug in 96.6%
      patients whereas rescue drug ephedrine was required in 36.6% patients in propofol
      group. Reduced induction doses 0.15mg kg(-1) for etomidate and 0.98 mg kg(-1) for
      propofol, sufficed to give an adequate anaesthetic depth based on entropy.
      CONCLUSION: Etomidate provides more hemodynamic stability than propofol during
      induction and intubation. Reduced induction doses of etomidate and propofol
      titrated to entropy translated into increased hemodynamic stability for both
      drugs and sufficed to give an adequate anaesthetic depth.

PMID- 25948898
TI  - Comparative evaluation of esmolol and dexmedetomidine for attenuation of
      sympathomimetic response to laryngoscopy and intubation in neurosurgical
      patients.
AB  - BACKGROUND AND AIMS: The present study compared the efficacy of esmolol and
      dexmedetomidine for attenuation of the sympathomimetic response to laryngoscopy
      and intubation in elective neurosurgical patients. MATERIAL AND METHODS: A total
      of 90 patients aged 20-60 years, American Society of Anesthesiologists physical
      status I or II, either sex, scheduled for elective neurosurgical procedures were
      included in this study. Patients were randomly allocated to three equal groups of
      30 each comprising of Control group (group C) 20 ml 0.9% saline intravenous (IV),
      group dexmedetomidine (group D) 1 MUg/kg diluted with 0.9% saline to 20 ml IV and
      group esmolol (group E) 1.5 mg/kg diluted with 0.9% saline to 20 ml IV. All the
      drugs were infused over a period of 10 min and after 2 min induction of
      anesthesia done. Heart rate (HR), systolic blood pressure, diastolic blood
      pressure, and mean arterial pressure were recorded baseline, after study drug
      administration, after induction and 1, 2, 3, 5, 10, and 15 min after orotracheal
      intubation. RESULTS: In group D, there was no statistically significant increase
      in HR and blood pressure after intubation at any time intervals, whereas in group
      E, there was a statistical significant increase in blood pressure after
      intubation at 1, 2, and 3 min only and HR up to 5 min. CONCLUSION:
      Dexmedetomidine 1 MUg/kg is more effective than esmolol for attenuating the
      hemodynamic response to laryngoscopy and intubation in elective neurosurgical
      patients.

PMID- 25948899
TI  - Comparative study of systemically and perineurally administered tramadol as an
      adjunct for supraclavicular brachial plexus block.
AB  - BACKGROUND AND AIMS: The study was designed to compare the effects of tramadol
      administered as an adjunct to bupivacaine in supraclavicular block to that of
      systemic administration, on postoperative analgesia and rescue analgesic
      requirement following upper limb surgeries. MATERIAL AND METHODS: A prospective,
      randomized, controlled, double-blind study was undertaken in patients scheduled
      for upper limb surgeries under supraclavicular block. All the three group
      patients received either of the following drugs mixtures: Group A - bupivacaine
      0.5%-18 ml + normal saline-7 ml for block and normal saline-10 ml intravenously.
      Group B - bupivacaine 0.5%-18 ml + normal saline-7 ml mixture for block and
      tramadol (100 mg) diluted to 10 ml - intravenously. Group C - bupivacaine 0.5%-18
      ml + tramadol (100 mg) + normal saline-5 ml mixture and normal saline 10 ml
      intravenously. The patients were observed for sensory, motor onset along with the
      duration of sensory and motor block. Patients were monitored for sedation and
      hemodynamic parameters during intra-operative and postoperative period. Pain-free
      period and demand for rescue analgesia was noted in all the patients. RESULTS:
      The study demonstrates that the mixture of tramadol and bupivacaine injected
      perineurally for supraclavicular brachial plexus block hastens the onset of
      sensory block, motor block and provides a longer duration of motor blockade and
      demand for rescue analgesia as compared to other two groups. CONCLUSIONS: In
      conclusion, the addition of tramadol to bupivacaine mixtures as an adjunct for
      supraclavicular brachial plexus block provide better postoperative analgesia for
      orthopedic upper extremity surgery in comparison to control or systemic tramadol
      group without any side effects.

PMID- 25948900
TI  - Preoperative anxiety in patients selecting either general or regional anesthesia
      for elective cesarean section.
AB  - BACKGROUND AND AIMS: We aimed to measure the frequency of preoperative anxiety in
      patients undergoing elective cesarean section (CS) and its impact on patients
      decision regarding the choice of anesthesia. MATERIAL AND METHODS: This cross
      sectional study included 154 consecutive patients, who were scheduled for
      elective CS. Visual analog scale (VAS) for anxiety was the study tool, and VAS
      >=50 was considered as significant anxiety. Enrolled patients were interviewed by
      the primary investigator the day before the surgery and their VAS score and
      choice of anesthesia technique either general anesthesia (GA) or regional
      anesthesia (RA) were recorded. Additional data included demographics, parity,
      educational status, previous anesthesia experience and source of information.
      RESULTS: Preoperative anxiety (VAS >= 50) was seen in 72.7% of patients, which
      was significantly higher (P < 0.005) in patients selecting GA (97.18%, n =
      71/154) as compared to those selecting RA (51.81%, n = 83/154) for elective CS.
      Statistically significant association of anxiety (P < 0.005) was seen with age
      <25 years, nulli and primiparous, higher education status, previous anesthesia
      experience and source of information from nonanesthetist. CONCLUSION: Patients
      scheduled for elective CS were found to have high frequency of anxiety (72.7%),
      and GA was observed to be the choice of anesthesia technique in anxious patients.

PMID- 25948889
TI  - Guidelines for diagnosis and management of bronchial asthma: Joint ICS/NCCP (I)
      recommendations.

PMID- 25948901
TI  - The dexmedetomidine "augmented" sedato analgesic cocktail: An effective approach
      for sedation in prolonged endoscopic retrograde cholangio-pancreatography.
AB  - BACKGROUND AND AIMS: In absence of any published standard guideline for sedation
      or anesthesia practice for prolonged therapeutic "endoscopic retrograde cholangio
      pancreatography (ERCP)", safe and cost-effective sedation protocol is the need of
      the hour. Our study aims to evaluate the efficacy of a dexmedetomidine as an add
      on for prolonged deep sedation for ERCP and to compare three deep sedation
      regimens regarding safety and efficacy. MATERIAL AND METHODS: Forty-five
      consecutively enrolled patients planned for therapeutic ERCP and assumed to have
      prolonged procedural duration (>50 min) were divided into three groups in a
      randomized assessor blinded fashion. Group 1 received propofol and midazolam,
      Group 2 received the sedato-analgesic cocktail containing ketamine-propofol
      midazolam-pentazocine, and the Group 3 received sedate-analgesic cocktail plus
      dexmedetomidine infusion under monitoring of vital parameters and according to
      the judgment of the concerned anesthesiologist. Total propofol requirement,
      episodes of gagging, oxygen desaturation, changes in mean blood pressure (MBP),
      recovery and satisfaction score of endoscopist, anesthetist and patient were
      noted and analyzed statistically using one way ANOVA with Bonferroni correction
      and Chi-square test. RESULTS: Mean propofol requirement, incidences of gagging
      and oxygen desaturation was significantly less in Group 2 and 3 compared to Group
      1. MBP was more stable and recovery was faster in Group 3. Anesthetist's
      satisfaction was more with Group 2 and even more with Group 3. CONCLUSIONS: The
      sedato-analgesic cocktail was superior to the conventional propofol-midazolam
      regimen, dexmedetomidine as add-on increased the efficacy and safety of sedate
      analgesic cocktail. It reduces propofol requirement, helps to maintain the
      patient in a safe and more stable level of sedation and increases satisfaction of
      the anesthetist.

PMID- 25948902
TI  - A comparison of the Mallampati test in supine and upright positions with and
      without phonation in predicting difficult laryngoscopy and intubation: A
      prospective study.
AB  - BACKGROUND AND AIMS: Difficult ventilation and intubation have been recognized as
      the forerunners of hypoxic brain damage during anesthesia. To overcome
      catastrophic events during anesthesia, an assessment of the airway before
      induction is of paramount importance. We designed this study to compare the
      effect of phonation on the Mallampati test in supine and upright positions as
      against the traditionally employed test without phonation in serving to predict
      difficult laryngoscopy and intubation. MATERIAL AND METHODS: In this cross
      sectional study, 661 patients aged 16-60 years were recruited during the years
      2011 to 2012. The Mallampati test was conducted on patients with and without
      phonation in both the sitting and supine positions. A blinded observer then
      performed laryngoscopy and intubation. Difficult intubation was assessed
      according to the Cormack-Lehane Grading scale. STATISTICAL ANALYSIS USED:
      Diagnostic statistical measures for each of the four situations - sensitivity,
      specificity, positive and negative predictive values and accuracy - were
      calculated. RESULTS: In this study, 28 patients (4.2%) had difficult laryngoscopy
      and nine patients (1.4%) had difficult intubation. There was no difference in the
      sensitivity of the Mallampati test as regards prediction of laryngoscopy and
      intubation in the four different positions, but the upright position along with
      phonation had the highest specificity. The negative predictive value was above
      95% in all the positions; however, the positive predictive value was the highest
      in the supine position along with phonation. CONCLUSION: Based on our results,
      the supine position along with phonation had the best correlation in the
      prediction of difficult laryngoscopy and intubation. We further conclude that
      phonation significantly improved the Mallampati class in the supine position
      compared with the upright position.

PMID- 25948903
TI  - Comparison between dexmedetomidine and fentanyl on intubation conditions during
      awake fiberoptic bronchoscopy: A randomized double-blind prospective study.
AB  - BACKGROUND AND AIMS: Various drugs are used for providing favorable intubation
      conditions during awake fiberoptic intubation (AFOI). However, most of them cause
      respiratory depression and airway obstruction leading to hypoxemia. The aim of
      this study was to compare intubation conditions, and incidence of desaturation
      between dexmedetomidine and fentanyl group during AFOI. MATERIAL AND METHODS:
      This randomized double-blind prospective study was conducted on a total of 60
      patients scheduled for elective laparotomies who were randomly allocated into two
      groups: Group A received dexmedetomidine 1 mcg/kg and Group B received fentanyl 2
      mcg/kg over 10 min. Patients in both groups received glycopyrrolate 0.2 mg
      intravenous, nebulization with 2% lidocaine 4 ml over 20 min and 10% lidocaine
      spray before undergoing AFOI. Adequacy of intubation condition was evaluated by
      cough score and post-intubation score. Incidence of desaturation, hemodynamic
      changes and sedation using Ramsay sedation scale (RSS) were noted and compared
      between two groups. RESULTS: Cough Score (1-4), post-intubation Score (1-3) and
      RSS (1-6) were significantly favorable (P < 0.0001) along with minimum
      hemodynamic responses to intubation (P < 0.05) and less oxygen desaturation (P <
      0.0001) in Group A than Group B. CONCLUSION: Dexmedetomidine is more effective
      than fentanyl in producing better intubation conditions, sedation along with
      hemodynamic stability and less desaturation during AFOI.

PMID- 25948904
TI  - Comparison of dexmedetomidine-propofol versus fentanyl-propofol for insertion of
      laryngeal mask airway.
AB  - BACKGROUND AND AIMS: Laryngeal mask airway (LMA) insertion requires anesthesia
      and suppression of airway reflexes. In search of an optimal drug, we compared
      dexmedetomidine and fentanyl, in combination with propofol for insertion of LMA.
      MATERIAL AND METHODS: This study was a prospective double blind randomized study.
      Eighty patients of ASA class 1&2 were randomly divided into two groups of 40
      each. Group D received dexmedetomidine 1 mcg/kg and group F received fentanyl 1
      mcg/kg intravenously (IV) over 2 minutes. For induction, propofol 2mg/kg was
      given IV and 90 seconds later LMA was inserted. We observed apnea time, heart
      rate, respiratory rate, non invasive blood pressure and oxygen saturation before
      induction, 30 seconds after induction, 1, 3, 5, 10 and 15 minutes after insertion
      of LMA. Patient's response to LMA insertion like coughing, gagging or any
      movement were noted and scored. Statistical analysis of data was done using
      student t test for parametric data, Chi-square test for non parametric data and
      SPSS 15.0 for windows software. RESULTS: 37 (92.5%) patients of group D and 35
      (87.5%) patients of group F had LMA insertion score of <2 and 5 (12.5%) patients
      of group F had score >2. Adverse events to insertion of LMA and hemodynamic
      variables were comparable in both the groups. Number of patients developing
      apnoea was larger and apnoea times were longer in group F compared to group D.
      When compared to group F, group D showed an increased respiratory rate.
      CONCLUSION: Dexmedetomidine can be a comparable alternative to fentanyl as an
      adjuvant to propofol for providing optimum insertion conditions for LMA and
      preservation of respiration.

PMID- 25948906
TI  - Comparison of Macintosh laryngoscope and C-MAC video laryngoscope for intubation
      in lateral position.
AB  - BACKGROUND AND AIMS: Endotracheal intubation is conventionally performed when the
      patient is in supine position. It may be required to secure airway in laterally
      positioned patient. Tracheal intubation in lateral position seems to be difficult
      because the laryngeal view is compromised. Hence, C-MAC video laryngoscope (Karl
      Storz, Germany), a newer device using a modified macintosh blade may be useful
      for intubation in lateral position. MATERIAL AND METHODS: A total of 100 American
      Society of Anesthesiologists Grade I and II patients, randomly allotted to C-MAC
      or direct laryngoscopy group. Patients with difficult airway were excluded. After
      induction of anesthesia, patient was put in right-lateral position and intubation
      was carried out by consultant who is well-versed in using C-MAC laryngoscope.
      Time for intubation, number of attempts, Modified Cormack - Lehane grade, mucosal
      injury, and external laryngeal manipulation applied were noted. STATISTICAL
      ANALYSIS: Demographics and baseline airway assessments were analyzed using
      summary statistics. Unpaired t-test was used to assess intubation time. Number of
      attempts, esophageal intubation, dental injury, mucosal injury, use of stylet,
      and application of external laryngeal manipulation were analyzed using Chi-square
      test. RESULTS: Overall intubation success rate was 100%. The time taken in C-MAC
      group was 24.8 +/- 8.5 s and in direct group was 33.8 +/- 9.12 s. The number of
      intubation attempts was not significant. Cormack - Lehane grade was better with C
      MAC laryngoscope. Mucosal injury and use of external laryngeal manipulation was
      more in direct group. CONCLUSION: C-MAC is better than Macintosh laryngoscope for
      intubation in lateral position.

PMID- 25948905
TI  - I-gel versus laryngeal mask airway-Proseal: Comparison of two supraglottic airway
      devices in short surgical procedures.
AB  - BACKGROUND AND AIMS: Supraglottic airway devices have been established in
      clinical anesthesia practice and have been previously shown to be safe and
      efficient. The objective of this prospective, randomized trial was to compare I
      Gel with LMA-Proseal in anesthetized spontaneously breathing patients. MATERIAL
      AND METHODS: Sixty patients undergoing short surgical procedures were randomly
      assigned to I-gel (Group I) or LMA- Proseal (Group P). Anesthesia was induced
      with standard doses of propofol and the supraglottic airway device was inserted.
      We compared the ease and time required for insertion, airway sealing pressure and
      adverse events. RESULTS: There were no significant differences in demographic and
      hemodynamic data. I-gel was significantly easier to insert than LMA-Proseal (P <
      0.05) (Chi-square test). The mean time for insertion was more with Group P (41 +
      09.41 secs) than with Group I (29.53 + 08.23 secs) (P < 0.05). Although the
      airway sealing pressure was significantly higher with Group P (25.73 + 02.21 cm
      of H2O), the airway sealing pressure of Group I (20.07 + 02.94 cm of H2O) was
      very well within normal limit (Student's t test). The success rate of first
      attempt insertion was more with Group I (P < 0.05). There was no evidence of
      airway trauma, regurgitation and aspiration. Sore throat was significantly more
      evident in Group P. CONCLUSION: I-Gel is a innovative supraglottic device with
      acceptable airway sealing pressure, easier to insert, less traumatic with lower
      incidence of sore throat. Hence I-Gel can be a good alternative to LMA-Proseal.

PMID- 25948907
TI  - Efficacy of contrasting background on a drug label: A prospective, randomized
      study.
AB  - BACKGROUND AND AIMS: Medication error can occur due to fault at any level
      starting from manufacturing until the administration to the patient. It can be
      difficult to read the drug name and other information from an ampoule, if there
      is poor contrast between the font color and background of the ampoule. Primary
      aim of this study was to evaluate the efficacy of the contrast color on the
      ampoule's label. MATERIAL AND METHODS: The study was conducted in a randomized
      blinded manner at a tertiary level trauma center. One hundred and eight resident
      doctors participated in the study. All the participants were divided into two
      groups after randomization. Group A was given the original drug ampoule while the
      modified ampoule with contrast was given to Group B. Total time in reading the
      ampoule and difficulty in reading (DR) scoring were noted for each participant.
      Another scoring regarding correct reading of ampoule was also noted and compared.
      STATISTICAL ANALYSIS: Student's t-test and Mann-Whitney test were used
      accordingly and P < 0.05 was considered as significant. RESULTS: It was found
      that mean time taken in reading the original ampoule was more compared to
      modified ampoule (11.64 +/- 1.48 vs. 9.48 +/- 1.62 seconds P < 0.05). DR score
      was also higher in Group A (P < 0.05) and correct reading score was more in Group
      B (P < 0.05). CONCLUSION: The labels on drug ampoules or vials should always have
      a contrasting background. This may reduce medication error and improve patient
      safety.

PMID- 25948908
TI  - A comparison of continuous infusion and intermittent bolus administration of 0.1%
      ropivacaine with 0.0002% fentanyl for epidural labor analgesia.
AB  - BACKGROUND AND AIMS: Minimal consumption of local anesthetic and opioid for
      epidural labor analgesia has been advocated for safe obstetric outcome and
      superior maternal satisfaction. The primary objective of this study was to
      evaluate and compare the analgesic efficacy of mode of administration of epidural
      0.1% ropivacaine with 0.0002% fentanyl via continuous infusion or intermittent
      boluses during labor. MATERIAL AND METHODS: Sixty term primi or second gravida
      healthy parturients in labor requesting epidural analgesia were recruited in this
      study. Lumbar epidural catheter was inserted, and analgesia initiated with 0.2%
      ropivacaine. Patients were randomized to receive ropivacaine 0.1% with fentanyl
      0.0002% via either continuous infusion (Group A) or intermittent boluses (Group
      B) on an hourly basis. If the parturient complained of pain and visual analog
      scale (VAS) score was >3, an additional bolus of the study drug was given. VAS
      score, motor blockade, maternal hemodynamics and fetal heart sounds were
      frequently monitored. Side effects, mode of delivery and neonatal outcome were
      noted. RESULTS: To achieve similar VAS, the mean total dose of ropivacaine was
      18.78 +/- 3.88 mg in Group A and 16.86 +/- 4.3 mg in Group B, the difference
      being statistically significant (P = 0.04). Seventeen out of 30 patients in Group
      A that is, 56.6% and nine patients in Group B that is, 30% required additional
      top-ups, and this was significantly higher (P = 0.037). Side effects, mode of
      delivery and neonatal outcome were comparable in both groups. CONCLUSION:
      Intermittent bolus administration provides a more efficacious route of drug
      delivery when compared to continuous infusion by significantly decreasing the
      total amount of local anesthetic plus opioid without adversely affecting patient
      safety or maternal satisfaction.

PMID- 25948909
TI  - Nasotracheal intubation with MacGrath videolaryngoscope using Schroeder
      directional stylet: Case series.
AB  - BACKGROUND AND AIMS: MacGrath videolaryngoscope is one of the recent
      videolaryngoscopes, which can be used to facilitate nasotracheal intubations
      using Scroeder directional stylet. MATERIAL AND METHODS: 15 patients, American
      Society of Anesthesiologists Grades I-II, undergoing tonsillectomy, requiring
      nasotracheal intubation were included. All patients were intubated with MacGrath
      videolaryngoscope and Schroeder stylet. Primary outcome measures were duration
      and ease of intubation. Overall success rate, number of attempts, modified
      Cormack-Lehane (C-L) grading, and complications were also recorded. RESULTS: All
      15 intubations were successful during first laryngoscopy attempt. C-L Grade I
      views were obtained in 14 patients (93%) and Grade II view in one patient (7%).
      The time required to obtain the best C-L view was 9.4 +/- 1.5 s. The time taken
      to complete tracheal intubation was 34.27 +/- 3.38 s. Average numerical rating
      scale for tracheal intubation was 8.7 +/- 0.9. Minor complications occurred in
      four patients (26.7%). CONCLUSIONS: MacGrath videolaryngoscope produces excellent
      laryngoscopic views in patients with normal airways. Impaction of tracheal tube
      on posterior nasopharyngeal wall can be overcome by Schroeder stylet.

PMID- 25948910
TI  - Finding the way into the burnt airway!

PMID- 25948911
TI  - Spinal subdural hematoma with cauda equina syndrome: A complication of combined
      spinal epidural anesthesia.
AB  - Combined spinal-epidural anesthesia (CSE) is considered safe in lower limb
      surgeries. We report a case of sudden neurological deterioration in a stable
      postoperative patient who was given CSE for total knee replacement and low
      molecular weight heparin in postoperative period. On the 4(th) postoperative day,
      she developed sudden onset weakness in left lower limb along with bladder
      incontinence. Magnetic resonance imaging spine revealed a subdural hematoma at L2
      L3 level. Immediate laminectomy along with cord decompression was done and
      patient recovered well except for a persistent foot drop on left side. 

PMID- 25948913
TI  - Anesthetic management of post-burn contracture chest with microstomia: Regional
      nerve blocks to aid in intubation.
AB  - This case report exemplifies the anesthetic technique of blocking bilateral
      infraorbital and mental nerves for release of contractures of mouth. A 30 year
      old female patient of post-acid burn contractures of chest wall and mouth was
      scheduled for contracture release and skin grafting. Airway assessment revealed
      severe restriction of mouth opening with limited restriction of neck movements.
      Contracture release of mouth conducted by blocking bilateral infraorbital and
      mental nerves, which facilitated intubation easily. This case report highlights
      the practical advantage of nerve blocks for release of contracture mouth, in case
      of anticipated difficult airway, over other conventional methods. 

PMID- 25948912
TI  - Complex pseudoaneurysm of ascending aorta: Unusual cause of right heart
      dysfunction-implications to the anesthesiologist.
AB  - Pseudoaneurysm of ascending aorta (PAA) is a rare complication occurring after
      cardiac surgery. Because of rarity of the condition, most standard teaching and
      anesthetic literature do not highlight on these postoperative aortic
      complications. Right heart dysfunction associated with PAA is scarcely reported.
      We describe here two cases of PAA with right heart involvement and discuss the
      possible anesthetic challenges. 

PMID- 25948914
TI  - Congenital hemihyperplasia with hemipigmentation: A rare presentation.
AB  - Hemihyperplasia is a heterogenous group of disorders characterized by asymmetric
      limb growth. Confusion regarding their classification and ascertainment into
      various syndromes still exists. Subtle, asymmetric variation of the unilateral
      structures of the head, face, trunk or extremities may occur in the general
      population in the absence of any local lesion or condition. 

PMID- 25948915
TI  - Truview PCD-video laryngoscope aided nasotracheal intubation in case series of
      orofacial malignancy with limited mouth opening.

PMID- 25948916
TI  - Pregabalin for refractory postdural puncture headache.

PMID- 25948917
TI  - Circuit leak with D-vapor.

PMID- 25948918
TI  - Acute intermittent porphyria.

PMID- 25948919
TI  - Noninvasive ventilation in a patient with noncardiogenic pulmonary edema
      following amlodipine poisoning.

PMID- 25948920
TI  - A rare case of postpoliomyelitis quadriparetic patient with severe
      kyphoscoliosis.

PMID- 25948921
TI  - Simulation based learning: Indian perspective.

PMID- 25948922
TI  - Simulation for "Evaluation" and teaching "Standard operating procedures".

PMID- 25948923
TI  - Inadvertent pneumothorax caused by intubating bougie.

PMID- 25948924
TI  - Airway management of a huge thyroid swelling with retrosternal extension by awake
      intubation using loco-sedative technique.

PMID- 25948925
TI  - Alternatives to GlideRite((r)) for flexometallic endotracheal tube insertion with
      GlideScope((r)).

PMID- 25948926
TI  - Trachlight-guided intubation in small infant with difficult airway.

PMID- 25948927
TI  - Internal jugular vein thrombosis: a complication of temporary hemodialysis
      catheter.

PMID- 25948928
TI  - Is visualization of dilator also important in central venous cannulation?

PMID- 25948929
TI  - A rare and deceptive venous anomaly, sinus pericranii.

PMID- 25948930
TI  - Anesthetic management of a patient with Wilms tumor, aniridia, genital anomalies
      and mental retardation syndrome undergoing right nephrectomy.

PMID- 25948931
TI  - Recurrent laryngeal nerve palsy following interscalene brachial plexus block: How
      to manage and avoid permanent sequelae?

PMID- 25948932
TI  - Benign intracranial hypotension: A new indication for epidural blood patch.

PMID- 25948933
TI  - Hyperventilation syndrome after general anesthesia.

PMID- 25948934
TI  - Surgical partial removal of papillomatosis for endotracheal intubation as an
      alternative to tracheostomy for an "almost completely" occluded airway.

PMID- 25948935
TI  - Evaluation of grading and hormone receptor immunostaining on fine needle
      aspirates in carcinoma breast.
AB  - BACKGROUND: Grading and hormone receptor determination in breast carcinoma are
      predictive factors for response to hormonal therapy. AIM: This study was
      undertaken to grade breast carcinoma and to determine estrogen receptor (ER) and
      progesterone receptor (PR) expression on fine-needle aspiration cytology (FNAC).
      Furthermore, the objective was to compare the results with histological grading
      and immunohistochemistry on surgical material. MATERIALS AND METHODS: Fifty cases
      of breast carcinoma diagnosed on FNAC were included. The cytological grading was
      done according to the Robinson's grading system. The corresponding histology
      sections were graded using the modified Bloom-Richardson system. Immunostaining
      for ER and PR was done on smears and tissue sections. RESULTS: On both
      cytological and histological evaluation, 49 cases were infiltrating ductal
      carcinoma and one case was colloid carcinoma. On comparing cytological and
      histological grading, 78% were correctly graded on cytology. The sensitivity,
      specificity, positive predictive value and negative predictive value for ER
      detection on immunocytochemistry (ICC) were 55.6%, 95%, 93.8% and 61.3%,
      respectively. The sensitivity, specificity, positive and negative predictive
      value for PR detection on ICC were 57.7%, 95.2%, 93.8% and 64.5%, respectively.
      The correlation for ER and PR between cytology and histology was 72.3% and 74.5%.
      CONCLUSION: The grading along with ER and PR immunostaining of breast carcinoma
      on smears is advocated because of high concordance between cytology and
      histology. This allows the patient to be treated with hormonal therapy on the
      basis of FNAC alone.

PMID- 25948936
TI  - Clinical audit of ultrasound guided fine needle aspiration in a general
      cytopathology service.
AB  - BACKGROUND: Studies on ultrasonography (USG) guided fine needle aspiration
      cytology (FNAC) have been conducted in specialized settings such as thyroid,
      breast, and intra-abdominal aspirates. There is a paucity of literature on the
      practices of guided FNAC in a general cytopathology service. AIM: The aim was to
      determine prevailing practices of USG guided FNAC in a general cytopathology
      service of a teaching hospital. SETTINGS AND DESIGN: Metropolitan hospital,
      clinical audit. MATERIALS AND METHODS: Audit of 112 USG guided percutaneous FNAC
      done over 12 months. STATISTICAL ANALYSIS: Data were coded, entered in an excel
      spreadsheet and analyzed by translating into percentages and proportions.
      RESULTS: The 112 guided FNACs included constituted 36 thyroid (32.14%), 45 intra
      abdominal (40.17%), 11 breast (9.82%), 10 superficial lymph node (8.92%) and 10
      soft tissue and miscellaneous (8.92%) lesions. Previous freehand FNAC was
      documented on the requisition forms in 14 cases. The reports were: Inadequate 33
      (29.46%), nondiagnostic descriptive 35 (31.25%) or diagnostic 44 (39.28%).
      Inadequacy rates of aspirates from thyroid were 11 (30.56%) breast were 2
      (18.18%), and intra-abdominal lesions were 13 (28.88%). Majority of the reports
      were nonstructured: 108 (96.42%) and nonrecommendatory: 101 (90.17%).
      CONCLUSIONS: Reporting practices varied and did not conform to a uniform
      structure. The inadequacy rates of breast and thyroid aspirates were comparable
      to the rates in the literature. Comparable studies were not available for intra
      abdominal aspirates.

PMID- 25948937
TI  - The Bethesda system for reporting thyroid cytopathology in Colombia: Correlation
      with histopathological diagnoses in oncology and non-oncology institutions.
AB  - AIM: To determine the correlation between the results of thyroid fine-needle
      aspirations interpreted using the Bethesda system and final histopathological
      reports for patients at an oncology hospital (OH) and non-oncology hospitals
      (NOHs). MATERIALS AND METHODS: A retrospective, cross-sectional, descriptive
      study was performed to compare the cytology and histopathology results for
      patients with thyroid nodules in three Colombian hospitals. The final correlation
      of diagnoses between the two methods is reported. In Colombia, the health system
      provides the existence of general care hospitals and hospitals specializing in
      care of patients with cancer. RESULTS: A total of 196 reports were reviewed, of
      which 53% were from OH and 47% were from NOHs. A greater proportion of category V
      (37.5%) was diagnosed at the OH, whereas NOHs diagnosed a greater proportion of
      category II (42.3%). The global correlation between diagnoses made using cytology
      and histopathology was 93.3% for categories V and VI (based on the final
      malignant diagnosis) and 86.9% for benign category II. Significant differences
      between institution types were observed when category IV and V and malignant
      histopathology were compared (56.3% OH vs. 23.5% NOH; P = 0.05 for category IV,
      97.4% OH vs. 82.3% NOH; P = 0.03 for category V), while no significant difference
      between institution types was observed when category II and final benign
      diagnosis were compared (P = 0.6). CONCLUSIONS: The Bethesda system for thyroid
      cytology correlates adequately with final histopathological diagnosis in
      Colombia. Significant differences were identified in the diagnostic correlation
      for malignant lesions between the OH and NOHs in categories IV and V caused by
      selection bias of the population.

PMID- 25948938
TI  - Efficacy of liquid-based cytology versus conventional smears in FNA samples.
AB  - BACKGROUND: Liquid-based cytology (LBC) is fast becoming a useful method in
      evaluating both gynecological and non-gynecological preparations, including fine
      needle aspiration (FNA) cytology. Even distribution of cells, decreasing
      obscuring background elements like blood and mucus, well preserved nuclear and
      cytoplasmic details and rapid fixation helps in better visualization of cells.
      AIM: This study was conducted to asses the diagnostic accuracy of liquid-based
      cytology versus conventional smears in fine needle aspiration samples. STUDY
      DESIGN: In this prospective study, we had 110 cases, including 30 cases of
      breast, 40 of lymph node, 10 of salivary glands, 18 of thyroid and 12 of bone and
      soft tissue. In each case, two passes were performed. The first pass was for
      conventional preparation (CP) and the second pass yielded material for thin-prep
      (TP) preparation. Both CP and TP smears were compared for cellularity, background
      blood and necrotic cell debris, cell architecture, informative background,
      presence of a monolayer of cells and nuclear and cytoplasmic details by a
      semiquantitative scoring system. Wilcoxon's signed rank test on an SPSS program
      was used for statistical analysis. RESULTS: Diagnostic accuracy was better in LBC
      smears compared with CP smears due to lack of background debris and better cell
      morphology, which was performed according to Wilcoxon's signed rank test,
      yielding a P-value of <0.001. However, in some cases, because of a decrease in
      cell size, clustering and altered background in LBC, a support of CP was
      essential. CONCLUSION: LBC performed on FNA samples can be a simple and valuable
      technique. Only in few selected cases, where background factor is an essential
      diagnostic clue, a combination of both CP and TP is necessary.

PMID- 25948939
TI  - Diagnostic challenges in cytology of mucoepidermoid carcinoma: Report of 6 cases
      with histopathological correlation.
AB  - BACKGROUND: Mucoepidermoid carcinoma (MEC) is a malignant salivary gland neoplasm
      with extreme morphologic heterogeneity and hence rendering a definitive fine
      needle aspiration cytology (FNAC) diagnosis of this neoplasm is really
      challenging. The present study was undertaken to elucidate the cytological
      features of MEC and explore the diagnostic accuracy and pitfalls by comparing
      with subsequent histopathology. MATERIALS AND METHODS: The present study was
      conducted over a period of 2 years wherein we obtained six histopathologically
      confirmed cases of MEC. These patients were initially subjected to FNAC. The
      cytologic features studied included presence of mucous cells, intermediate cells,
      and squamous cells. Presence of background mucinous material was also noted. The
      cytological features were compared with the subsequent histopathology. RESULTS:
      Of the 6 cases of MEC, a definite cytological diagnosis was possible only in 2
      cases. Of the remaining 4 cases, 2 cases were broadly diagnosed in cytology as
      neoplasm with cystic degeneration and 2 cases were underdiagnosed as pleomorphic
      adenoma. CONCLUSIONS: A satisfactory aspirate with all three types of cells;
      mucous, intermediate and squamous cells may not be obtained in all cases of MEC
      for providing a definite diagnosis. Hence, a good clinicoradiological
      correlation, a high index of suspicion and repeated aspirations especially in
      cystic lesions may be particularly helpful in difficult cases. In addition, while
      dealing with mucinous cystic lesions with low cellularity, the importance of
      early excision should be communicated to the clinician since the possibility of
      low-grade MEC cannot be excluded.

PMID- 25948940
TI  - Unusual cytomorphology of acute suppurative thyroiditis.

PMID- 25948941
TI  - Vertebral metastases from giant cell carcinoma of lung: Images in cytopathology.

PMID- 25948942
TI  - Upregulation of NKX2.2, a target of EWSR1/FLI1 fusion transcript, in primary
      renal Ewing sarcoma.
AB  - Renal Ewing sarcoma (ES) is a rare malignant tumor characterized by fusion of the
      EWSR1 gene with a member of the ETS family of oncogenes, arising at a specific
      chromosomal translocation. Diagnosis of ES can be problematic, especially from
      cytological or small bioptical specimens because the differential diagnoses
      comprising a diverse group of small round blue cell tumors (SRBCTs). We report a
      case of primary renal ES in a young male, which had a t(11;22) (q24;q12)
      chromosome translocation encoding a type2 EWSR1/FLI1 fusion transcript. The tumor
      cells showed diffuse cytoplasmic immunoreactivity for CD99 and diffuse nuclear
      immunoreactivity for NKX2.2, an important oncogenic transcriptional target of
      EWSR1/FLI1, not only in the histological, but also in the cytological specimens.
      From the results of this case, we speculate that NKX2.2, in combination with
      CD99, may be a useful immunocytochemical marker to distinguish renal ES from
      other SRBCTs of kidney. 

PMID- 25948944
TI  - Primary hepatic lymphoma: A case report.
AB  - Primary non-Hodgkin lymphoma of the liver is a very rare malignancy. In this case
      report, we describe a case of primary hepatic lymphoma (PHL) in a 60-year-old man
      who presented with lump and pain in the abdomen of 2 months' duration. The
      patient had altered liver function, normal serum alfa fetoprotein level (AFP),
      normal hemogram and bone marrow. A computed tomography scan of the abdomen and
      pelvis showed an ill-defined hypodense mass with specks of calcification
      involving the liver, suggestive of primary malignant mass of liver. Diagnosis of
      PHL was established on the cytology smear and confirmed by immunohistochemistry
      on tissue biopsy. This case demonstrates that PHL should be considered in the
      differential diagnosis of space-occupying liver lesions in the presence of a
      normal level of AFP. Fine needle aspiration cytology is a faster and safer
      diagnostic modality even in such a rare case. The case has many unique features
      like negative serology for viruses, no type B symptom and normal lactate
      dehydrogenase level. 

PMID- 25948943
TI  - Cytopathological features of matrix-producing carcinoma of the breast.
AB  - Matrix producing carcinoma (MPC) of the breast is a very rare subtype of
      metaplastic carcinoma with heterelogous elements, which comprises <0.1% of
      invasive breast carcinomas. There are very few reports describing the cytological
      features of MPC. In this article, we aimed to discuss cytological,
      histopathological and immunohistochemical features of this rare entity in a 59
      year-old woman. 

PMID- 25948945
TI  - Cytological diagnosis of superficial acral fibromyxoma: A case report.
AB  - Superficial acral fibromyxoma (SAF) is a rare, distinctive benign soft tissue
      lesion that often involves the fingers and toes, with the great toe being the
      most frequently affected site. We report a case of SAF diagnosed by fine needle
      aspiration cytology and confirmed by histopathology. The pre-operative
      cytological diagnosis will help the surgeon to plan for a wider excision that
      prevents recurrence. 

PMID- 25948946
TI  - Myxopapillary ependymoma: Lesser known cytomorphologic features.
AB  - Myxopapillary ependymoma (MPE) is a rare and distinctive tumor which occurs in
      the sacrococcygeal area of young adults and children, often intradural in
      location. Histopathologic features have been well-described in the literature
      whereas cytological findings have been sporadically reported by various authors
      mainly as case reports. We report the features of a primary sacrococcygeal MPE on
      aspirate cytology in a 45-year-old female. Cytology smears displayed a papillary
      pattern with the presence of fibrovascular cores, rimmed by cuboidal to columnar
      cells sending fibrillary cytoplasmic processes forming pseudorosettes along with
      the presence of hyaline globules, and myxoid material. Intranuclear inclusions,
      nuclear grooves, cytologic atypia or mitotic activity was not evident, in this
      case. MPEs need to be differentiated from the other tumors occurring in this
      location which may also show myxoid material and papillary fronds. Hence, the
      recognition of the characteristic cytologic features plays an important role in
      establishing a preoperative diagnosis. 

PMID- 25948947
TI  - Unusual morphology of desmoplastic small round cell tumor from an ascitic fluid
      in the postchemotherapy setting.
AB  - Desmoplastic small round cell tumor (DSRCT) is a malignant neoplasm that most
      often presents in male adolescents as an abdominal mass. Cytological features
      have been previously described, but only two reports noted post chemotherapy
      changes on effusions. We report a case of a 15-year-old male with DSRCT status
      postchemotherapy that presented with ascitis. Unusual morphology was seen:
      Numerous malignant large and single cells with prominent nucleoli and abundant
      cytoplasm in a background without the stroma, occasional mitosis, and the
      abundant apoptosis. Cell block immunocytochemistry was confirmatory. Awareness of
      the postchemotherapy changes in this tumor will allow us to diagnose recurrence. 

PMID- 25948948
TI  - A rare association of Sarcina with gastric adenocarcinoma diagnosed on fine
      needle aspiration.
AB  - Sarcina is a Gram-positive anaerobic organism, having exclusively fermentative
      metabolism and has been associated with gastric outlet obstruction. We
      demonstrate the present case to highlight the presence of Sarcina with a
      coexisting gastric adenocarcinoma diagnosed on fine needle aspiration cytology. 

PMID- 25948949
TI  - Yolk sac tumor of cryptorchid testis diagnosed by fine needle aspiration
      cytology.
AB  - Yolk sac tumor is the most common germ cell tumor in infants and children.
      Majority of them arise in the gonads. Yolk sac tumor of undescended testis has
      been rarely diagnosed. We present a case of yolk sac tumor in right undescended
      testis in a 2-year-old child primarily diagnosed by fine needle aspiration
      cytology. 

PMID- 25948950
TI  - Primary pulmonary synovial sarcoma: Diagnosis on squash smears.
AB  - Synovial sarcomas are rare tumors accounting for approximately 5-10% of soft
      tissue sarcomas. They occur predominantly in the extremities, followed by head
      and neck. Primary pulmonary sarcomas are very rare and comprise only 0.5% of all
      primary lung malignancies. The diagnosis is established only after sarcomas like
      primary lung malignancies, and metastatic sarcomas have been excluded. For
      synovial sarcomas that arise at unusual locations, a definitive diagnosis is
      challenging and requires the use of ancillary diagnostic procedures such as
      immunohistochemistry (IHC) and molecular genetic techniques for confirmation of
      diagnosis. We report a case of 29-year-old male who had right lower lobe lung
      mass. He underwent right lower lobectomy. Intraoperative squash smears revealed
      spindle cell sarcoma. Subsequent histopathology and IHC confirmed the diagnosis
      as synovial sarcoma. We report this case on account of its rarity and to
      emphasize the utility of intraoperative squash smears in the diagnosis of such
      cases, which has been under-utilized in clinical practice. 

PMID- 25948951
TI  - Polymorphous low grade adenocarcinoma of lip clinically mimicking squamous cell
      carcinoma: An unusual presentation.
AB  - Polymorphous low grade adenocarcinoma (PLGA) is a malignant neoplasm that
      frequently occurs in the minor salivary glands in palate and oral cavity. We
      present a case of upper lip swelling with ulceroproliferative growth, clinically
      mimicking squamous cell carcinoma (SCC). Fine-needle aspiration cytology smears
      suggested PLGA, which was later confirmed on histopathology. Clinical
      presentation of PLGA may simulate SCC. 

PMID- 25948952
TI  - Cytological findings of an extragonadal yolk sac tumor presenting at an unusual
      site.
AB  - Yolk sac tumor (YST) is a rare neoplasm that affects children and adolescents.
      Fine needle aspiration biopsy is an extremely useful procedure for the diagnosis
      of YST. Main objective is to describe the characteristic cytological features of
      fine needle aspirates of YST. We report a case of YST in a 4-year-old male child
      occurring at paravertebral region showing cytomorphological details. 

PMID- 25948953
TI  - Scar endometriosis: Diagnosis by fine needle aspiration.
AB  - Endometriosis is defined as the presence of a functioning endometrium outside the
      uterus. Abdominal wall endometriosis is a rare entity. Most of the abdominal wall
      endometriosis occurs in or around surgical scars following caesarean section or
      hysterectomy. We report a case of scar endometriosis following caesarean section
      and diagnosed by fine needle aspiration cytology (FNAC). Excision biopsy
      confirmed the FNAC diagnosis of scar endometriosis. 

PMID- 25948954
TI  - Papular skin lesions: Clue to a recurrence of breast cancer on fine needle non
      aspiration cytology (FNNAC).
AB  - Cutaneous metastasis from underlying carcinoma is relatively uncommon in clinical
      practice. A high index of suspicion is required to diagnose these lesions, as
      these lesions can mimic benign skin lesions and clinical findings may be subtle.
      Fine needle aspiration cytology (FNAC) is commonly employed for diagnosing these
      skin lesions. However, it is often difficult to aspirate adequate material from
      small papular lesions. In these clinical situations, fine needle non-aspiration
      cytology (FNNAC) is proposed as an alternative procedure. FNNAC eliminates the
      negative suction pressure employed in FNAC and decreases the dilution of tumor
      cells by blood and hence yields adequate diagnostic material. We report here a
      case in which FNNAC was used in place of FNAC in diagnosing papular skin lesions.
      This procedure was carried out in a treated patient of carcinoma breast who was
      on regular follow-up and presented to us with a 20-day history of papular skin
      lesions over the chest and back. This article enlightens the clinicians about the
      utility of FNNAC, which is a relatively uncommon procedure. 

PMID- 25948955
TI  - Role of fine needle aspiration cytology and cell block in diagnosis of scar
      endometriosis: A case report.
AB  - Presence of endometrial glands and stroma in places other than the uterus is
      called endometriosis. It can be pelvic or extra-pelvic. Abdominal scar
      endometriosis is an extra-pelvic endometriosis that can occur after surgery
      involving the uterus. Post-caesarean section, scar endometriosis is a rare event.
      The diagnosis is frequently made only after excision of disease tissue. We
      present a case of post-caesarean section abdominal scar endometriosis presenting
      as a tumor on the abdominal wall, which was diagnosed by fine needle aspiration
      cytology and confirmed by cell block preparation. 

PMID- 25948956
TI  - Small cell carcinoma in common bile duct brushing: A rare cytopathological
      diagnosis.

PMID- 25948957
TI  - Plasmacytoid appearance of tumor cells in breast aspirates on fine needle
      aspiration cytology: Diagnostic predicament for the cytopathologist.

PMID- 25948958
TI  - Comparison of the species-sensitive effects of different dosages of calcium and
      verapamil on gentamicin-induced nephrotoxicity in rats and rabbits.
AB  - AIM: To compare the effects of different dosages of calcium and verapamil on
      gentamicin-induced nephrotoxicity in rats and rabbits. MATERIALS AND METHODS:
      Rabbits and rats of either sex in weight range of 1.5-2.5 kg and 175-225 g,
      respectively were used in study. Gentamicin 80 mg/kg i.m., calcium carbonate 0.5
      g/kg/day oral, calcium carbonate 1.0 g/kg/day oral, and verapamil 7 mg/kg/day
      i.m. were administered for 6 days in either species containing 7 groups. Blood
      urea nitrogen (BUN), serum creatinine and, urine protein levels were assessed on
      day 0 and day 7 for kidney function. The animals were sacrificed on day 7 for
      histopathplogical examination and kidney superoxide dismutase levels (SOD) were
      measured. Statistical analysis was done using student's unpaired t-test, analysis
      of variance (ANOVA) and Wilcoxon Rank Sum test. P-value less than 0.05 was
      considered significant. RESULTS: The results showed that calcium was able to
      reverse significantly increased BUN, serum creatinine, urine protein, and reduced
      kidney SOD levels in gentamicin-treated nephrotoxic rats or rabbits in a dose
      dependent manner while verapamil had no protective or nephrotoxic effect.
      CONCLUSION: Calcium 0.5 g/kg/day and 1.0 g/kg/day were able to reverse tubular
      necrosis and mesangial proliferation in gentamicin-treated nephrotoxic animals.
      There was no species-sensitive variation in reversal of nephrotoxicity by calcium
      in rats and rabbits.

PMID- 25948959
TI  - Protective effect of curculigo orchioides extract on cyclophosphamide-induced
      neurotoxicity in murine model.
AB  - Free radicals are one of the frequent products of normal cellular metabolism.
      Disparity of metabolism and excessive generation of free radicals predisposes to
      disorders like Parkinson's disease, Alzheimer's disease, and aging phenomenon.
      Curculigo orchioides Gaertn. is known for "adaptogen" and "aphrodisiac" activity
      and has been proved for antiasthmatic, estrogenic, antiosteoporotic activity
      along with protection from cisplatin-induced cell damage. C. orchioides was
      powdered and subjected to soxhlet extraction using methanol. Phytochemical
      studies and estimation of polyphenols and flavonoids was performed. Acute
      toxicity studies were performed by Organization for Economic Cooperation and
      Development OECD guidelines. Animals were treated with cyclophosphamide to induce
      neurotoxicity. Curculigo orchioides was powdered and subjected to soxhlet
      extraction using methanol. Catalase, superoxide dismutase, glutathione
      peroxidase, and lipid peroxidation were estimated by reported methods. C.
      orchioides (400 mg/kg) significantly promoted restoration of catalase (P <
      0.005), superoxide dismutase (P < 0.005), and glutathion (P < 0.05) levels.
      Similarly, a very significant decrease (P < 0.005) in the levels of
      malondialdehyde was observed. In all cases as mentioned previously, C. orchioides
      at dose 200 mg/kg promoted significant (P < 0.05) restoration of enzyme levels.
      C. orchioides (Kali Musli) is rich source of phytochemicals like flavonoids and
      polyphenols. Flavonoids and polyphenols are reputed to demonstrate
      neuroprotective effect. These phytochemicals in the present study might be
      responsible to demonstrate neuroprotective effect. 

PMID- 25948960
TI  - Genetic variation associated with hypersensitivity to mercury.
AB  - OBJECTIVES: Very little is known about mechanisms of idiosyncratic sensitivity to
      the damaging effects of mercury (Hg); however, there is likely a genetic
      component. The aim of the present study was to search for genetic variation in
      genes thought to be involved in Hg metabolism and transport in a group of
      individuals identified as having elevated Hg sensitivity compared to a normal
      control group. MATERIALS AND METHODS: Survivors of pink disease (PD; infantile
      acrodynia) are a population of clinically identifiable individuals who are Hg
      sensitive. In the present study, single nucleotide polymorphisms in genes thought
      to be involved in Hg transport and metabolism were compared across two groups:
      (i) PD survivors (n = 25); and (ii) age- and sex-matched healthy controls (n =
      25). RESULTS: Analyses revealed significant differences between groups in
      genotype frequencies for rs662 in the gene encoding paraoxanase 1 (PON1) and
      rs1801131 in the gene encoding methylenetetrahydrofolate reductase (MTHFR).
      CONCLUSIONS: We have identified two genetic polymorphisms associated with
      increased sensitivity to Hg. Genetic variation in MTHFR and PON1 significantly
      differentiated a group formerly diagnosed with PD (a condition of Hg
      hypersensitivity) with age- and gender-matched healthy controls.

PMID- 25948961
TI  - Assessment of genotoxic potential of hridayarnava rasa (a herbo-mineralo-metallic
      ayurvedic formulation) using chromosomal aberration and sperm abnormality assays.
AB  - OBJECTIVES: Herbo-mineral formulations are being successfully used in
      therapeutics since centuries. But recently, they came under the scanner for their
      metallic contents especially the presence of heavy metals. Hence it is the need
      of the hour to assess and establish the safety of these formulations through
      toxicity studies. In line with the various toxicity studies that are being
      carried out, Government of India expressed the need for conducting genotoxicity
      studies of different metal- or mineral-based drugs. Till date very few Ayurvedic
      herbo-mineral formulations have been studied for their genotoxic potential. The
      present study is aimed to evaluate the genotoxic potential of Hridayarnava Rasa.
      MATERIALS AND METHODS: It was prepared as per classical guidelines and
      administered to Swiss albino mice for 14 consecutive days. Chromosomal aberration
      and sperm abnormality assay were done to evaluate the genotoxic potential of the
      test drugs. Cyclophosphamide (CP) was taken as positive group and results were
      compared. RESULTS: All treated groups exhibited significant body weight gain in
      comparison to CP group. Results revealed no structural deformity in the above
      parameters in comparison to the CP-treated group. CONCLUSION: Reported data
      showed that both tested samples of Hridayarnava Rasa does not possess genotoxic
      potential under the experimental conditions and can be safely used.

PMID- 25948962
TI  - Assessment of Mycotoxin Exposure in Cote d'ivoire (Ivory Coast) Through Multi
      Biomarker Analysis and Possible Correlation with Food Consumption Patterns.
AB  - SCOPE: The aim of the presented study was to investigate the mycotoxin exposure
      of Ivorian population related to the consumption patterns of maize, peanuts,
      millet, and cassava product (attieke). MATERIALS AND METHODS: Maize flour samples
      (n = 51) were purchased from all Abidjan local markets, in the south of Ivory
      Coast, and urine (n = 99) was collected during the same reference period (July
      September 2011) from volunteers living in Abidjan and Daloa cities. Reversed
      phase liquid chromatography coupled with electrospray ionization triple
      quadrupole mass spectrometry (LC-ESI-MS/MS) was used to analyze aflatoxins (AFB1,
      AFB2, AFG1, and AFG2), ochratoxin A (OTA), fumonisins (FB1, FB2), deoxynivalenol
      (DON), zearalenone (ZEA), and T-2 and HT-2 toxins in maize flour samples, and
      their relevant biomarkers (AFM1, DON, DON + de-epoxydeoxynivalenol (DOM-1), FB1,
      alpha-zearalenol (ZOL), beta-ZOL, and OTA) in urine samples. RESULTS: Critical
      maize contamination was observed by AFs occurrence (total AFs 4.5 - 330.0 MUg/kg)
      while OTA was found in 13% of samples analyzed. AFM1 was detected in 40% of
      urines samples (0.06 - 14.11 ng/ml), OTA in 37% (0.01 - 0.42 ng/ml), FB1 in 27%
      (0.07 to 15.31 ng/ml) and, DON was found in 21% of samples at levels up to 10.0
      ng/ml. The correlation coefficients (R(2)) obtained by plotting the percentage of
      biomarker occurrence (positive samples) versus the frequency of food consumption
      revealed maize, peanuts, millet and attieke were strongly linked to AFB1 and OTA
      exposure with values of R(2) ranged from 0.462 to 0.956. CONCLUSION: The present
      study provided data on mycotoxin risk in Ivory Coast, revealing a frequent co
      exposure to the major mycotoxins such as AFs, OTA, and fumonisins, which appeared
      to be related to the frequency of peanuts, maize, millet and attieke consumption.

PMID- 25948963
TI  - Antimutagenic effect of dioscorea pentaphylla on genotoxic effect induced by
      methyl methanesulfonate in the Drosophila wing spot test.
AB  - OBJECTIVES: Plants as dietary sources are known to have several chemoprotective
      agents. Dioscorea pentaphylla is an important medicinal plant, which is often
      used as edible food. This study was undertaken to evaluate the antigenotoxic
      potential of D. pentaphylla extracts on the genotoxic effect induced by methyl
      methanesulfonate (MMS) in the Drosophila wing spot test. MATERIALS AND METHODS:
      The somatic mutation and recombination test (SMART) was carried out in Drosophila
      melanogaster. In transheterogyous larvae, multiple wing hair (mwh 3-0.3) and
      flare (flr3-38.8) genes were used as markers of the extent of mutagenicity.
      RESULTS: It was observed thatall the three extracts (petroleum ether,
      choloroform, and ethyl alcohol) in the combined treatment had significantly
      inhibited the effect of MMS-induced genotoxic effects. When compared to others,
      the ethanol extract showed a very significant antimutagenic activity. CONCLUSION:
      The compounds that are present in the extracts may directly interact with the
      methyl radical groups of MMS and inactivate them by chemical reaction. It is also
      possible that the compounds in the extract compete to interact with the
      nucleophilic sites in deoxyribonucleic acid (DNA), thus altering the binding of
      the mutagen to these sites. Although our results indicate that the compounds
      present in the extracts may directly interact with the methyl radical groups of
      MMS and inactivate them by chemical reaction, it may also be quite interesting to
      investigate through the other different mechanisms by which D. pentaphylla could
      interfere in vivo on the effect of genotoxic agents.

PMID- 25948964
TI  - A study on neurobehavioral performance of workers occupationally exposed to
      solvent in synthetic resin manufacturing.
AB  - BACKGROUND: One major effect of occupational solvent exposure is central nervous
      system (CNS) impairment, ranging from depression to encephalopathy with
      cognitive, behavioral changes. Exposures in industries being varied,
      classification of health outcomes for different exposures is important.
      OBJECTIVES: This study assessed neurobehavioral performance of synthetic resin
      manufacturing workers exposed to organic solvent, mainly formalin. MATERIALS AND
      METHODS: This cross-sectional study selected subjects by random selection from
      all such workers of an Indian city. Questionnaire survey and assessment by a
      neurobehavioral test battery (NBT) was undertaken. RESULTS: Comparison between
      actual and allied workers observed significant difference in tweezer dexterity,
      card sorting and backward memory scores. Significant effect of exposure was
      observed on tweezer dexterity, card sorting, and hand dynamometer scores.
      CONCLUSION: Changes of neurobehavioral performance might occur following solvent
      exposure and these changes might have a relationship with the quantum of
      exposure. Periodic examination of workers with NBT is needed for detection of
      early neurotoxic effects.

PMID- 25948965
TI  - A Systematic Study on Structure and Function of ATPase of Wuchereria bancrofti.
AB  - BACKGROUND: Analyzing the structures and functions of different proteins of
      Wuchereria bancrofti is very important because till date no effective drug or
      vaccine has been discovered to treat lymphatic filariasis (LF). ATPase is one of
      the most important proteins of Wuchereria bancrofti. Adenosine triphosphate (ATP)
      converts into adenosine diphosphate (ADP) and a free phosphate ion by the action
      of these ATPase enzymes. Energy releases from these dephosphorylation reactions
      drive the other chemical reactions in the cell. MATERIALS AND METHODS: In this
      study we worked on the protein ATPase of Wuchereria bancrofti which has been
      annotated from National Center for Biotechnology Information (NCBI). Various
      computational tools and databases have been used to determine the various
      characteristics of that enzyme such as physiochemical properties, secondary
      structure, three-dimensional (3D) structure, conserved domain, epitope, and their
      molecular evolutionary relationship. RESULT: Subcellular localization of ATPase
      was identified and we have found that 55.5% are localized in the cytoplasm.
      Secondary and 3D structure of this protein was also predicted. Both structure and
      function analysis of ATPase of Wuchereria bancrofti showed unique nonhomologous
      epitope sites and nonhomologous antigenicity sites. Moreover, it resulted in 15
      ligand drug-binding sites in its tertiary structure. CONCLUSION: Structure
      prediction of these proteins and detection of binding sites and antigenicity
      sites from this study would indicate a potential target aiding docking studies
      for therapeutic designing against filariasis.

PMID- 25948966
TI  - Rifapentine-proliposomes for inhalation: in vitro and in vivo toxicity.
AB  - BACKGROUND: Oral therapy for pulmonary tuberculosis (TB) treatment suffers from
      the limitation of hepatic metabolism leading insufficient concentration of
      antitubercular (anti-TB) drugs in alveolar macrophage which harbors Mycobacterium
      tuberculosis (MTB). Targeted aerosol delivery of antituberculous drug to lung is
      efficient for treating local lung TB infection. OBJECTIVE: The present study was
      aimed to evaluate rifapentine (RPT) loaded proliposomal dry powder for inhalation
      (RLDPI) for anti-TBactivity and cytotoxicity in vitro. In vivo toxicity study was
      also undertaken in Wistar rats to determine safe concentration of RLDPI for
      administration. MATERIALS AND METHODS: Anti-TB activity of developed RLDPI was
      assessed using drug susceptibility testing (DST) on Mycobacteria growth indicator
      tube (MGIT) method. In vitro cytotoxicity was performed in A549 cell lines and
      IC50 values were used to compare the cytotoxicity of formulation with pure RPT.
      In vivo repeated dose toxicity study was undertaken using Wistar rats at three
      different doses for 28-days by intratracheal insufflations method. RESULTS: The
      results of DST study revealed sensitivity of tubercle bacteria to RLDPI at
      concentration equivalent to 10 MUg/mL of RPT. This study confirmed anti-TB
      potential of RPT in spray-dried RLDPI, though the spray drying method is reported
      to reduce activity of drugs. Cytotoxicity study in A549 cells demonstrated that
      RPT when encapsulated in liposomes as RLDPI was safe to cells as compared to pure
      RPT. In vivo toxicity study revealed that RPT in the form of RLDPI was safe at 1
      and 5 mg/kg dose. However, mortality was seen at higher dose (10 mg/kg), possibly
      because of liver and kidney damage. CONCLUSION: Thus, these studies demonstrated
      safety of RLDPI for the treatment of pulmonary TB.

PMID- 25948967
TI  - Hematobiochemical evaluation of dermal subacute cypermethrin toxicity in buffalo
      calves.
AB  - Dermal exposure of cypermethrin, a type II synthetic pyrethroid insecticide, at
      dose rate of 0.25% for 14 consecutive days produced mild signs of toxicity in
      buffalo calves. It produced significant elevation in the levels of alanine
      aminotransferase (ALT; 39.5%), aspartate aminotransferase (AST; 32.0%), blood
      urea nitrogen (BUN; 57.7%), and plasma creatinine (30.0%). Cypermethrin also
      produced significant decrease in the hemoglobin (Hb) concentration (5.4%), packed
      cell volume (PCV; 3.4%), and total erythrocytic count (4.0%). Additionally, there
      was a significant increase in erythrocytic sedimentation rate (ESR; 3.1%). On the
      basis of the present study, it can be concluded that cypermethrin induces
      significant biochemical and hematological alterations in buffalo calves when
      exposed dermally. 

PMID- 25948968
TI  - Hematological Alterations on Sub-acute Exposure to Flubendiamide in Sprague
      Dawley Rats.
AB  - BACKGROUND: Pesticide poisoning is a common occurrence around the world.
      Pesticides can act on various body systems resulting in toxicity. Flubendiamide
      is a new generation pesticide, reported to have better activity against
      Lepidopteran insects. The present study was carried out with an objective to
      analyze the effects of flubendiamide sub-acute exposure on hematology of rats.
      MATERIALS AND METHODS: Male and female Sprague Dawley (SD) rats (9-11 weeks) were
      divided into five groups with six animals in each group. First group served as
      control, while the rest were exposed to ascending oral doses of flubendiamide
      (125, 250, 500 and 1000 mg/kg) for 28 days. After the trial period, blood was
      collected in heparinized vials and analyzed using Siemens ADVIA 2120((r))
      autoanalyzer. Various erythrocytic, platelet and leukocyte parameters were
      measured and analyzed using statistical tests by one-way analysis of variance
      (ANOVA) and t-test using Statistical Package for Social Sciences (SPSS)((r)) 20
      software. RESULTS: After processing the data through statistical analysis, it was
      observed that the effect of flubendiamide exposure on female rats was negligible.
      The only significant change observed in the female rats was that in total
      erythrocytic count, while rest of the parameters showed non-significant
      bidirectional changes. In males, many parameters viz., total leukocyte count
      (TLC), total erythrocyte count (TEC), packed cell volume (PCV), mean corpuscular
      volume (MCV), platelet count (PC), mean platelet volume (MPV), platelet
      distribution width (PDW), hemoglobin distribution width (HDW), large platelets
      (LPT) and plateletcrit (PCT) expressed significant difference when compared to
      control. CONCLUSION: Many of the changes were dose independent, but sex specific.
      This lead to the hypothesis that saturation toxicokinetics might be one of the
      reasons for this varied response, which can only be evaluated after further
      testing.

PMID- 25948969
TI  - Protective effects of dioscorea alata L. In aniline exposure-induced spleen
      toxicity in rats: a biochemical study.
AB  - INTRODUCTION: Present study was designed to evaluate the protective effects of
      ethanolic extract of Dioscorea alata L. (DA) on hematological and biochemical
      changes in aniline-induced spleen toxicity in rats. MATERIALS AND METHODS: Wistar
      rats of either sex (200-250g) were used in the study and each group contains six
      rats. Splenic toxicity was induced in rats by administration of aniline
      hydrochloride (AH; 100 ppm) in drinking water for a period of 30 days. Treatment
      groups received DA (50 and 100 mg/kg/day, po) along with AH. At the end of
      treatment period, various serum and tissue parameters were evaluated. RESULT:
      Rats administered with AH (100 ppm) in drinking water for 30 days showed a
      significant alteration in general parameters (organ weight, body weight, water
      intake, feed consumption, and fecal matter content), hematological parameters
      (red blood cell (RBC), white blood cell (WBC), and hemoglobin content), and
      biochemical parameters (total iron content, lipid peroxidation, reduced
      glutathione (GSH), and nitric oxide (NO) content) of spleen. Treatment with DA
      (50 and 100 mg/kg/day, po) for 30 days along with AH showed significant recovery
      in aniline-induced splenic toxicity. CONCLUSION: The present result showed that
      involvement of oxidative and nitrosative stress in aniline-induced splenic
      toxicity and DA protects the rats from the toxicity, which might be due to its
      antioxidant property and the presence of different phytochemicals.

PMID- 25948970
TI  - Investigating the Association between Angiogenic Cytokines and Corneal
      Neovascularization in Sulfur Mustard Intoxicated Subjects 26 Years after
      Exposure.
AB  - OBJECTIVES: This study aimed to evaluate the associations between the
      concentrations of three major angiogenic cytokines-vascular endothelial growth
      factor-A165 (VEGF-A165), basic fibroblast growth factor (bFGF), and platelet
      derived growth factor-BB (PDGF-BB)-in the tear of sulfur mustard (SM)-exposed
      subjects and corneal neovascularization (CNV) 26 years after exposure. MATERIALS
      AND METHODS: The concentrations of VEGF-A, bFGF, and PDGF-BB were measured by
      enzyme-linked immunosorbent assay (ELISA) in reflex tears of (i) SM-injured
      patients with CNV (positive case group including 18 individuals) and (ii) SM
      injured patients without CNV (negative case group including 22 individuals). Then
      results were compared to corresponding values obtained from tears of 40 healthy
      control subjects. RESULTS: The mean concentrations of all investigated growth
      factors, VEGF-A165, bFGF, and PDGF-BB, were significantly higher in positive
      cases than controls (P <= 0.001, P = 0.028, and P = 0.041, respectively).
      Whereas, VEGF-A165 was the only growth factor which displayed significantly
      elevated concentrations in negative case group compared to the healthy
      individuals (P = 0.030). Additionally, the mean level of VEGF-A165 was also
      higher in positive patient group than negative patients (P = 0.022). Subjects
      with increased concentrations of tear VEGF-A165 were more than 10 times more
      likely to suffer from CNV than normal individuals (odds ratio (OR) = 10.43,
      confidence interval (CI): 2.14-38.46, P = 0.001), while elevated levels of bFGF
      and PDGF-BB increased the risk of CNV by about twofold. CONCLUSION: Although all
      investigated cytokines had increased in tears of positive patients, VEGF-A was
      the only one which showed a significant correlation with the severity of CNV, and
      thus played a crucial role in corneal angiogenesis.

PMID- 25948971
TI  - Antioxidant Properties of the Extracts of Talinum Triangulare and its Effect on
      Antioxidant enzymes in Tissue Homogenate of Swiss Albino Rat.
AB  - OBJECTIVES: This study was designed to put into consideration both the in vitro
      and in vivo investigations on Talinum triangulare (Tt), an herbaceous perennial
      plant that is a native of tropical America and one of the most important
      vegetables in Nigeria. METHODS: Total phenolic contents in (mg GAE/100 g),
      flavonoid contents, the ferric reducing antioxidant properties (FRAP), 2, 2
      diphenyl-1-picrylhydrazyl (DPPH), hydroxyl free radical scavenging ability (OH-)
      and iron chelating ability were carried out in vivo using standard described
      methods while GSH, GPx, catalase and SOD were determined in vivo using standard
      described methods. RESULTS: In the three different solvents extraction of T.
      triangulare that were studied in vitro, it was noted that ethyl acetate and
      ethanolic fractions of T. triangulare showed potent antioxidant activity against
      DPPH and iron chelating property with high phenolic content except Hydroxyl free
      radical scavenging ability that showed highest value in the aqueous extract,
      while the Reduced GSH indicated the highest in the parameter determined in vivo.
      CONCLUSION: The antioxidant properties showed in this solvent extractable
      component probably could have been the basis for the enhanced activities of
      antioxidant enzymes at very lower dose in the examined tissue homogenates.
      Therefore, T. triangulare can thereby serve as a means of Preventing some of
      major degenerative diseases challenging Humans.

PMID- 25948972
TI  - Naphthalene poisoning manifesting as hemoglobinuria.
AB  - Reddish black discoloration of urine in absence of red blood cells (RBCs) can be
      a manifestation of hemoglobinuria or myoglobinuria. We report a patient who was
      admitted for persistent vomiting. On 2(nd) day of admission, his urine turned
      reddish black. The patient then revealed that he had ingested mothballs 1 day
      back to commit suicide. The patient was managed conservatively with intravenous
      (IV) fluids and antiemetics. Mothballs are rarely reported as a suicidal agent
      and most cases are related to accidental exposure of children while playing. IV
      hemolysis is also reported with mothball ingestion. Our patient quickly became
      normal within 24 h and there was no residual organ damage. 

PMID- 25948973
TI  - Fatal case of hydrocarbon aspiration and use of lipoid cells as corroborative
      finding for rapid autopsy diagnosis in cases of delayed death.
AB  - Accidental aspiration of diesel can cause consolidation, atelectasis, and abscess
      formation. Aspiration of diesel usually results into pneumonitis, which resolves
      completely within 5-7 days of treatment. Diesel aspiration resulting in bilateral
      pneumonia and death is rare and is scarcely documented in literature. Finding of
      lipoid cells in lung autopsy specimen is one of the important features of
      hydrocarbon aspiration. Unfortunately this important finding is not mentioned in
      most of the toxicology textbooks. Hence, we are reporting this case. 

PMID- 25948974
TI  - Pheniramine Maleate-Induced Rhabdomyolysis and Aki: Is it Fatal?
AB  - Pheniramine maleate is an easily accessible, over-the-counterantihistaminic,
      which is frequently involved in overdoses. Pheniramine has antimuscarinic effect
      causing tachycardia, dilated pupils, urinary retention, and dry flushed skin, and
      decreased bowel sounds, confusion, mild increase in body temperature, cardiac
      arrhythmias, and seizures at lethal doses. It has not been implicated as an
      important cause of rhabdomyolysis and acute kidney injury (AKI). Rhabdomyolysis
      causing AKI is rarely reported in the literature. This case report emphasizes the
      occurrence of nontraumatic rhabdomyolysis in pheniramine maleate overdose which
      required hemodialysis. Since there is a lack of a specific antidote, treatment is
      mainly symptomatic and supportive. We report a fatal case of a young male with a
      very high dose of consumption of pheniramine maleate (4.077 g), which was
      complicated by seizures, respiratory depression, nontraumatic rhabdomyolysis, and
      AKI. Despite hemodialysis, ventilator support, and other intensive supportive
      care, patient could not survive and death ensued due to multiorgan dysfunction
      syndrome. 

PMID- 25948975
TI  - Conservative care in successful treatment of abamectin poisoning.
AB  - Human intoxication with abamectin is an uncommon but potentially fatal cause of
      pesticide poisoning. In this study a 42-year-old man was intoxicated with 3600 mg
      abamectin orally. On admission patient was fully alert with the smell of the
      poison from the mouth. Vital signs were normal and conjunctiva was hyperemic.
      Conservative cares such as gastric lavage was performed and charcoal was
      administered. After 2.5 hours, the patient gradually developed altered mental
      status as drowsiness, hypotension, tachycardia and dermal erythema. He was
      treated with H1 and H2 blockers and vasoactive agents and after 2 days was
      discharged in good condition. In comparison with organophosphates, abamectin
      intoxication has less risk in humans. However, consumption of large amounts in
      human can be fatal. Altered mental status could be considered as the first sign
      of abamectin intoxication. Normal level of consciousness is the best indicator of
      improvement of the condition. Conservative treatment is recommended. 

PMID- 25948976
TI  - Adrenal hematoma and right hemothorax after echis carinatus bite: an unusual
      manifestation.
AB  - Common bleeding manifestations after viperine bite include bleeding from site of
      bite, bleeding gums, epistaxis, hemoptysis, hematuria, hematemesis, and
      intracranial bleed. Bleeding in the adrenal gland is a rare manifestation. We
      report here a patient of viperine bite who developed right adrenal hematoma and
      right hemothorax after 3 days of bite. To the best of our knowledge this is the
      first case report of adrenal hematoma and right hemothorax after Echis carinatus
      bite. 

PMID- 25948977
TI  - Glyphosate poisoning with acute pulmonary edema.
AB  - GlySH-surfactant herbicide (GlySH), one of the most commonly used herbicides
      worldwide, has been considered as minimally toxic to humans. However, clinical
      toxicologists occasionally encounter cases of severe systemic toxicity. The US
      Environmental Protection Agency (EPA) states that 'GlySH' is of relatively low
      oral and acute dermal toxicity. It does not have anticholinesterase effect and no
      organophosphate-like central nervous system (CNS) effects. The clinical features
      range from skin and throat irritation to hypotension and death. Severe GlySH
      surfactant poisoning is manifested by gastroenteritis, respiratory disturbances,
      altered mental status, hypotension refractory to the treatment, renal failure,
      and shock.[1] GlySH intoxication has a case fatality rate 3.2-29.3%. Pulmonary
      toxicity and renal toxicity seem to be responsible for mortality. Metabolic
      acidosis, abnormal chest X-ray, arrhythmias, and elevated serum creatinine levels
      are useful prognostic factors for predicting GlySH mortality.[2] There is no
      antidote and the mainstay of treatment for systemic toxicity is decontamination
      and aggressive supportive therapy. We report a case of acute pulmonary edema,
      which is a rare but severe manifestation of oral GlySH poisoning, where patient
      survived with aggressive supportive therapy. 

PMID- 25948978
TI  - Suicidal ingestion of potassium permanganate crystals: a rare encounter.
AB  - Potassium permanganate poisoning is not common. Although Symptoms of potassium
      permanganate ingestion are gastrointestinal and Complications due to ingestion of
      potassium permanganate include cardiovascular depression, hepatic and renal
      damage, upper airway obstruction, bleeding tendency and methemoglobinemia.
      Gastric damage due to potassium permanganate has rarely been reported previously.
      We are reporting a 34-year old female patient who presented to our Emergency
      Department after suicidal ingestion of potassium permanganate crystals. After
      treatment, the patient was discharged home on the 8(th) day after admission. So
      we conclude that Emergency endoscopy has a significant role in diagnosis and
      management of potassium permanganate ingestion. 

PMID- 25948979
TI  - Dose-dependent olanzapine-induced myoclonus.
AB  - Second-generation antipsychotics (SGA), mainly clozapine have been reported to
      induce myoclonus. Although olanzapine-induced myoclonus is reported, dose
      dependent response has not been described. We report dose-related olanzapine
      induced myoclonus in an early onset schizophrenia patient. We also suggest
      certain management strategies for such adverse side effects. 

PMID- 25948980
TI  - Successful management of rodenticide induced acute liver failure in a patient.

PMID- 25948981
TI  - The 'golden hour' in paraquat poisoning.

PMID- 25948982
TI  - Preferred methods of suicide and most common poisonings in India.

PMID- 25948983
TI  - From the editor's desk.

PMID- 25948984
TI  - Lymphoglandular bodies.

PMID- 25948985
TI  - Desmosomes: A light microscopic and ultrastructural analysis of desmosomes in
      odontogenic cysts.
AB  - INTRODUCTION: Desmosomes together with adherens junctions represent the major
      adhesive cell-cell junctions of epithelial cells. Any damage to these junctions
      leads to loss of structural balance. AIM: The present study was designed to
      analyze the desmosomal junctions in different odontogenic cysts and compare them
      with their corresponding hematoxylin and eosin (H and E)   stained sections.
      MATERIALS AND METHODS: Ten cases each of odontogenic keratocyst (OKC),
      dentigerous cysts (DCs), radicular cysts (RCs) and normal mucosa were stained
      with hematoxylin and eosin. Scanning electron microscopy (SEM) analysis of the
      sections was then carried out of all the sections. The area of interest on H and
      E stained section was marked and this marking was later superimposed onto the
      corresponding unstained sections and were subjected to SEM analysis. RESULTS AND
      OBSERVATIONS: OKC at *1000 magnification showed many prominent desmosomes.
      However, an increase in the intercellular space was also noted. SEM analysis
      demonstrated similar findings with the presence of many desmosomes, though they
      were seen to be damaged and fragile. H and E stained DC under oil immersion did
      not show any prominent desmosomes. SEM analysis of the same confirmed the
      observation and very minimal number were seen with a very condense arrangement of
      the epithelial cells. RC at *1000 magnification revealed plenty of desmosomes,
      which were again confirmed by SEM. CONCLUSION: The number and quality of
      desmosomal junctions in all the cysts has a role in the clinical behavior of the
      cyst.

PMID- 25948986
TI  - Expression of CD34 and CD68 in peripheral giant cell granuloma and central giant
      cell granuloma: An immunohistochemical analysis.
AB  - BACKGROUND: Central and Peripheral giant cell granulomas of jaws are uncommon,
      benign, reactive disorders that are characterized by the presence of numerous
      multinucleated giant cells and mononuclear cells within a stroma. The origin of
      the multinucleated giant cells is controversial; probably originating from fusion
      of histiocytes, endothelial cells and fibroblasts. OBJECTIVE: To assess the
      expression of CD34 and CD68 in central and peripheral giant cell granulomas to
      understand the origin of these multinucleated giant cells. MATERIALS AND METHODS:
      Twenty cases of Central and Peripheral giant cell granulomas were evaluated
      immunohistochemically for CD34 and CD68 proteins expression. RESULTS:
      Immunopositivity for CD34 was seen only in cytoplasm of endothelial cells of
      blood vessels; whereas, consistent cytoplasmic immunopositivity for CD68 was seen
      in few stromal cells. Statistical significance was seen in mean number of
      multinucleated giant cells, mean number of nuclei in multinucleated giant cells,
      CD68 expression and ratio of macrophages to multinucleated giant cells among two
      lesions. CONCLUSION: Although the central giant cell granulomas share some
      clinical and histopathological similarities with peripheral giant cell
      granulomas, differences in mean number of nuclei in multinucleated giant cells
      and CD68 immunoreactivity may underlie the distinct clinical behavior.

PMID- 25948987
TI  - Immunomorphological patterns of cervical lymph nodes in oral squamous cell
      carcinoma.
AB  - CONTEXT: Squamous cell carcinoma (SCC) comprises 80% of the cancers of the oral
      cavity. Metastases to the cervical lymph nodes affects prognosis. Studying lymph
      node reactivity may help to understand host immune reaction against the tumor and
      thus influence prognosis. AIMS: This study observed patterns of lymph node
      reactivity, metastases and grades of metastases in cervical lymph nodes and
      compared them with the histopathology of the primary tumor. MATERIALS AND
      METHODS: Lymph nodes from 30 patients of oral squamous cell carcinoma (OSCC) were
      taken. 10 of these were well-differentiated SCC (WDSCC), 10 moderately
      differentiated SCC (MDSCC) and 10 poorly differentiated SCC (PDSCC). Four
      immunomorphological patterns were observed: lymphocyte predominance, germinal
      centre predominance, mixed pattern (sinus histiocytosis) and unstimulated
      pattern. STATISTICAL ANALYSIS USED: Chi square test. RESULTS: The predominant
      lymph node reactive patterns were germinal centre predominance (79.27%),
      unstimulated pattern (14.63%) and lymphocyte predominance (6.10%). Positive nodes
      showed invasion in the form of islands (57.14%), cords (39.29%) and total
      replacement pattern (3.57%). Tumor involvement in positive nodes showed grade 3
      invasion, (53.57%), grade 2 invasion (26.79%), grade 4 invasion (17.86%) and
      grade 1 invasion (1.79%). Statistically significant association was found
      between: Lymph node reactive pattern and histopathological grade of primary
      tumor. Higher numbers of germinal centre predominance lymph nodes were found in
      WDSCC and MDSCCHistopathological grade of primary tumor and the grade of lymph
      node invasion. CONCLUSIONS: Immuno-morphological assessment of draining lymph
      nodes reflects the immune status of the patient with respect to metastases. This
      may facilitate identification of high and low risk patients and help in planning
      appropriate therapy for the high-risk patients.

PMID- 25948988
TI  - Efficacy of stereomicroscope as an aid to histopathological diagnosis.
AB  - Grossing and microscopic examination of the received specimens in a
      histopathological laboratory is a routine procedure for achieving a fi nal
      diagnosis. Errors in either of the steps may lead to an inaccurate diagnosis
      since wrong orientation of the specimen may either cause diagnostic delays or
      pose a diagnostic dilemma. Stereomicroscope is an important accessory instrument
      which can be used to study a variety of specimens. It not only enables us to
      study the surface details but also aids in minute work including dissection and
      microsurgery to name a few. AIM: To assess the effectiveness of stereomicroscope
      in routine grossing and its role in arriving at a final diagnosis. MATERIALS AND
      METHODS: Cases from the archives of the department for which stereomicroscopic
      evaluation was done were retrieved and reviewed. RESULTS AND CONCLUSION:
      Stereomicroscopic images aided not only in the proper orientation of the specimen
      but also in the diagnosis.

PMID- 25948989
TI  - Detection of salivary interleukin-2 in recurrent aphthous stomatitis.
AB  - OBJECTIVE: The present study was undertaken to estimate and compare salivary
      interleukin-2 (IL-2) levels in patients with recurrent aphthous stomatitis, among
      healthy controls and their variation with age and sex. STUDY DESIGN: Saliva was
      collected from 60 patients within the age range of 16-60 years which included 30
      patients (17 Females and 13 Males) with recurrent aphthous stomatitis and healthy
      control group consisted of 30 participants (18 Females and 12 Males). IL-2
      estimation was done in both the groups using enzyme linked immunosorbent assay
      (ELISA). Statistical analysis of the data was done using Independent 't' test.
      RESULTS: The results showed increased salivary IL-2 levels in patients with
      recurrent aphthous stomatitis compared to the healthy controls. The IL-2 levels
      were also increased in patients with the age group of 16-30 years compared to
      other age groups. Similar increase of IL-2 was also seen in female patients.
      CONCLUSION: Age related and sex related alterations of IL-2 in recurrent aphthous
      stomatitis patients were observed.

PMID- 25948990
TI  - Cytokeratin 14 and cytokeratin 18 expressions in reduced enamel epithelium and
      dentigerous cyst: Possible role in oncofetal transformation and histogenesis- of
      follicular type of adenomatoid odontogenic tumor.
AB  - INTRODUCTION: Odontogenic cysts and tumors arise from the structures and remnants
      associated with tooth development. Cysts and tumors derived from the odontogenic
      tissues constitute an unusually diverse group of lesions. This diversity reflects
      the complex development of the dental structures, since all these lesions
      originate through some alteration from the normal pattern of odontogenesis.
      Cytokeratin (CK) 14 is the typical intermediary filament of odontogenic
      epithelium, CK 18 is the major components of the intermediate filaments of simple
      or single layered epithelial tissue; it is not expressed in stratified squamous
      epithelium. The present study was undertaken to understand the expression pattern
      of these cytokeratins in dentigerous cyst, dental follicular tissue, adenomatoid
      odontogenic tumor (AOT) and unicystic ameloblastoma. MATERIALS AND METHODS: The
      present study consists of 60 specimens consisting of 20 samples of Dentigerous
      cyst, 20 samples of Reduced enamel epithelium/dental follicles, 10 samples of
      Follicular type of AOT, 10 samples of unicystic ameloblastoma. The sections of
      these specimens were stained for CK 14 and CK 18. The number of cells positive
      for CK 14 and CK 18 was counted per 100 cells. The cells were counted in four
      randomly selected high-power fields and the mean was calculated. Scoring of
      cytokeratin 14 expressions was done using Remmele score. RESULTS: The highest
      expression of cytokeratin 14 was noted in AOT, least was seen in dental
      follicle/Reduced enamel epithelium (REE). CK18 was negative in all the cases
      included in the present study. CONCLUSION: In the present study, the expression
      of CK14 was noted in AOT, Dentigerous cyst (DC), Unicystic Ameloblastoma (UCA)
      and Dental follicle/REE. The expressions between these lesions were compared.
      These expression pattern may provide an insight to the histogenesis of AOT.

PMID- 25948991
TI  - Glut-1 as a prognostic biomarker in oral squamous cell carcinoma.
AB  - INTRODUCTION: Glut-1 is a glucose transporter protein, the expression of which is
      upregulated in malignant cells which show increased glucose uptake. Alterations
      in expression of Glut-1 have been reported in several pre-malignant and malignant
      lesions. The objectives of the present study were to compare the expression of
      Glut-1 in normal persons and in patients with oral squamous cell carcinoma
      (OSCC), to correlate the expression of Glut-1 with respect to clinical staging of
      OSCC and to evaluate the expression of Glut-1 with respect to different
      histopathological grades of OSCC. MATERIALS AND METHODS: Thirty cases of OSCC
      were staged clinically and graded histopathologically. Immunohistochemical method
      was used to detect the expression of Glut-1 in OSCC and the same was compared
      with the normal subjects. The scores were compared using the chi-square test.
      RESULTS: Glut-1 expression was detected in all grades of OSCC. A significant
      correlation with a P value of 0.00004 was found in immunostaining between normal
      and OSCC. The expression of Glut-1 was significant when compared with different
      clinical stages with significant P value of 0.0004 and in different
      histopathological grades of OSCC with a P value of 0.00001. CONCLUSION: Higher
      immunohistochemical staining scores were obtained with increased clinical staging
      and histopathological grades of OSCC. High expression of Glut-1 may be related to
      poor prognosis in OSCC.

PMID- 25948992
TI  - Epithelial and stromal patterns of pleomorphic adenoma of minor salivary glands:
      A histopathological and histochemical study.
AB  - BACKGROUND: Pleomorphic adenoma (PA) accounts for 45-74% of all the salivary
      gland neoplasms, of which 40-70% are present in minor salivary glands. Studies
      have depicted variations in histological typing and classification of these
      tumors. Its pleomorphism is attributed to the cytological differentiations of the
      epithelial components and the diverse stromal components. Biochemical
      investigations of saliva have revealed "mucins" to be its main component. Mucins
      reflect in their composition, the functional state of the mucosa, both in health
      and disease. Many reviews on histochemical classification and identification have
      been put forward to explain the intricacies of mucins; however, no attempts have
      been made to classify salivary gland tumors based on their mucin profiles and
      assess its prognostic significance. Thus, this study was executed to analyze the
      clinical, histopathological and histochemical behavior of PA of minor salivary
      glands and decipher a correlation. MATERIALS AND METHODS: Twenty-six diagnosed
      cases of PA of minor salivary glands and five controls of normal minor salivary
      glands of the hard palate were included in the study. Blocks were retrieved,
      sectioned and stained with hematoxylin and eosin (H and E) stain as well as
      combined Alcian blue (AB)-periodic acid-Schiff (PAS) stains. RESULTS: The stained
      slides revealed an array of epithelial and stromal patterns and varying
      heterogeneity of mucin expression of normal and neoplastic minor salivary glands.
      CONCLUSION: The study elucidated the role of mucins in tumorigenesis and its
      prognostic implications.

PMID- 25948993
TI  - Evaluation of the orofacial lesions in treated leprosy patients.
AB  - BACKGROUND: Leprosy is primarily a disease of developmental countries. About 4
      million people have or are disabled by leprosy. Eighty-six percent of leprosy
      patients reside in Southeast Asia and Brazil. India accounts for up to 70% of
      total cases. AIM: To evaluate the incidence of orofacial lesions in treated
      leprosy patients. MATERIALS AND METHODS: Thirty treated leprosy patients were
      examined clinically and the percentage of orofacial lesions were evaluated.
      RESULTS: On evaluating the orofacial lesions, incidence of hypopigmentation on
      face and oral mucosa were highest (63%) followed by depressed nasal bridge and
      fissured tongue (33%). The incidence of crenated tongue was seen to be the lowest
      (3.3%). CONCLUSION: Orofacial lesions in leprosy patients develop insidiously,
      generally are asymptomatic and are secondary to nasal changes. Oral lesions may
      contribute to the diagnosis of the disease and be attributed to involvement of
      Mycobacterium leprae.

PMID- 25948994
TI  - Diagnostic procedures for autoimmune vesiculobullous diseases: A review.
AB  - Oral soft tissues are affected by numerous pathologic conditions of variable
      etiology and hence their appropriate management relies on their accurate
      diagnosis. Clinical identification of intact vesicle and bulla in the oral cavity
      is really a challenge due to the regular irritation and the friable nature of
      oral mucosa. Rupture of these lesions leads to erosions or ulcerations on the
      surface, hence making the diagnosis of vesiculobullous (VB) lesions is even more
      difficult due to the fact that the differential diagnosis along with VB lesions
      will also include ulcerative, immunological-mediated diseases, and neoplasms and
      systemic diseases. Hence, knowledge of the clinical presentation of these
      disorders and the relevant diagnostic procedures is important not just for
      dermatologists, but also for general practitioners and dentists. In this article,
      the various procedures have been explained that can be used for the diagnostic
      purpose of VB lesions. 

PMID- 25948995
TI  - Pigmented odontogenic tumors: Adding color to diagnosis?
AB  - Melanocytes are neural crest derivatives that exhibit a ubiquitous presence in
      the epidermis. They determine the complexion of an individual and most
      importantly, provide a barrier against ultraviolet radiations from the sun. Their
      presence in the oral cavity is a consistent finding, especially in the gingiva
      and buccal mucosa of the dark complexioned. Melanocytes occasionally form a part
      of the histology of a variety of odontogenic cysts and tumors. How these cells
      make their way into the lesional tissue and the diagnostic relevance of their
      presence remains elusive. This write up attempts to trace the path melanocytes
      take to find themselves within odontogenic tumors and also offer possible
      explanations for the same. 

PMID- 25948996
TI  - An update on intraoral application of colposcopy.
AB  - Colposcopy is an established technique for diagnosis in gynecology. Many
      premalignant and malignant lesions in these areas have discernible
      characteristics which can be detected using a colposcope, providing an enlarged
      view of the areas, allowing the colposcopist to visually distinguish normal from
      abnormal appearing tissue and take directed biopsies for further pathological
      examination. The diagnosis of a dysplastic lesion of the oral mucosa cannot be
      based solely on clinical findings. Therefore, histological evaluation of a
      representative biopsy specimen is necessary. The site for the biopsy is a
      subjective choice that sometimes raises doubts about its representativeness. So
      far, no simple and reliable method is available for selecting the most
      appropriate area for biopsy. Intraoral microscopy (oral application of the
      colposcopy technique) of mucosal lesions seems to offer advantages in selecting
      more representative sites for biopsy than routine clinical examination alone. The
      biopsy sites identified by direct oral microscopy show more advanced histologic
      signs than those selected by routine clinical examination. This article
      enlightens the application of colposcopy in diagnosis of oral premalignant
      lesions and malignant lesions. 

PMID- 25948997
TI  - Gorham's disease: A diagnostic challenge.
AB  - Gorham's disease is a rare disorder of uncertain etiology characterized by
      spontaneous and progressive osteolysis of one or more skeletal bones. Till date,
      less than 200 cases have been reported in the international literature with about
      51 cases involving the maxillofacial site. The radiographic findings associated
      with Gorham's disease are particularly dramatic, as in some cases a complete
      resorption of the involved bone can occur, leading to the definition of phantom
      bone or disappearing bone disease. The purpose of this review is to make our
      community aware of this rare entity and to discuss the etiopathology, clinical
      presentation, radiographic findings, histopathology, differential diagnoses and
      treatment modalities for patients with vanishing bone disease. 

PMID- 25948998
TI  - A rare occurrence of Langerhans cell histiocytosis in an adult.
AB  - Langerhans Cell Histiocytosis (LCH) is a disease process characterized by
      accumulation and infiltration of cells, showing ultrastructural and
      immunohistochemical similarities to Langerhans' cell, in the affected tissues. It
      exhibits extreme clinical heterogeneity. LCH was historically divided into 3
      clinical entities based on extent of tissue involvement and severity of
      presentation. These 3 entities were eosinophilic granuloma, Hand-Schuler
      Christian disease, Letterer-Siwe disease. Owing to similarities of their
      histologic appearance, they were grouped together under the term histiocytosis X.
      It was recently changed to LCH, emphasizing the primary cell involved in the
      disease process. LCH is a rare disease with an incidenceestimated to be 4.0 to
      5.4 per million population. Males are affected twice as frequently as females.
      The disease may occur at any age with peak incidence in children aged 1 to 3
      years. We describe an unusual case of a 65-year-old man who presented with
      painless swelling in anterior region of mandible. 

PMID- 25948999
TI  - Necrotizing sialometaplasia: A diagnostic dilemma!
AB  - Necrotizing sialometaplasia (NS) is a benign, self-limiting inflammatory reaction
      of salivary gland tissue which may mimic squamous cell carcinoma or
      mucoepidermoid carcinoma, both clinically and histologically, that creates
      diagnostic dilemma leading to unwarranted aggressive surgery. Most commonly
      affected site is the minor salivary glands of the palate. The pathogenesis is
      unknown but is believed to be due to ischemia of vasculature supplying the
      salivary gland lobules. A simple incisional biopsy is required to confirm the
      histological diagnosis and to rule out more serious disease processes. It is a
      self-limiting disease process and requires no treatment. It will be prudent to do
      repeat biopsy in case if the lesion does not heal within 3 months. 

PMID- 25949000
TI  - Chondrosarcoma of maxilla.
AB  - Chondrosarcoma (CHS) is a rare malignant neoplasm of the jaws. Based on the
      morphologic features alone, a correct diagnosis of CHS may be difficult.
      Therefore, correlation of radiological and clinicopathological features are
      mandatory for the diagnosis of CHS. A case of CHS of the maxilla is reported. A
      brief discussion on the etiopathogenesis, radiologic and histologic presentation
      of the tumor and the treatment modalities of this unusual tumor is discussed. 

PMID- 25949001
TI  - Primary intraosseous mucoepidermoid carcinoma of maxilla.
AB  - Primary intraosseous mucoepidermoid carcinoma (PIOC) of the jaw bones is an
      extremely rare malignant salivary gland tumor, comprising 2-3% of all
      mucoepidermoid carcinomas reported. It is commonly seen in the posterior part of
      the mandible; its occurrence in the maxilla is rare. They have been reported in
      patients of all ages, ranging from 1 to 78 years, with the overwhelming majority
      occurring in the 4th and 5th decades of life. They are histologically low-grade
      cancers and radiographically seen as uniocular or multiocular lesions. We report
      a rare case of PIOC in posterior palatal region in 18-year-old male. 

PMID- 25949002
TI  - Parosteal osteosarcoma: Report of a rare juxtacortical variant of osteosarcoma
      affecting the maxilla.
AB  - Parosteal osteosarcomas are rare, low-grade juxtacortical variant of
      osteosarcoma, especially in the jaws, representing 1.6% of all bony malignant
      tumours and upto 5% of all osteosarcomas. Only 12 cases of intraoral parosteal
      osteosarcomas have been reported in the English literature. In the jaws males are
      more commonly affected with peak occurrence at 39 years and nearly equal site
      predilection for maxilla and mandible. Radiographically, parosteal osteosarcomas
      are radiodense, lobulated masses with a broad stalk to the cortex of the bone
      with no periosteal reaction and medullary invasion. Microscopically, shows well
      differentiated tumor with minimum atypia and rare mitotic figures separating
      trabeculae of woven bone. Unlike classical and periosteal osteosarcoma, it is
      considered to have a good prognosis. A case report of this rare entity in 22-year
      old female patient with bony hard, painless swelling of 9 months duration in
      maxillary premolar-molar region is presented. The need for differential
      diagnostic approach is emphasized from other seemingly benign clinical entities. 

PMID- 25949003
TI  - Multiple granular cell tumors with metachronous occurrence in tongue and vulva.
      Clinicopathological and immunohistochemical study.
AB  - Granular cell tumor (GCT) usually occurs as a single tumor, although sometimes
      multiple lesions can occur. In present report we analyze the clinicopathological
      and immunohistochemical features of a multiple GCT involving the tongue of a 14
      year-old girl, with no other abnormalities, with a metachronous occurrence of a
      second GCT in vulva, after a period of 10 years. Both tumors revealed S-100,
      vimentin and CD57 positivity. In addition, over expression of calretinin was
      observed in tumor cells located in the vicinity of pseudoepitheliomatous
      hyperplasia (PEH) of the tongue. Tumor vasculature situated close to the PEH
      showed marked CD105 reactivity, data not described so far, suggesting an
      interaction between PEH cells and underlying stroma, since GCT completely lacks
      CD105 vessels. Our study emphasizes that patients with GCT, especially young
      patients, should be followed long-term, looking for multiple tumors or other
      abnormalities suggestive of a systemic syndrome, given the associations described
      in multiple GCT. 

PMID- 25949004
TI  - An unusual presentation of clear cell odontogenic carcinoma in mandibular
      anterior region.
AB  - Clear cell odontogenic carcinoma (CCOC) is a rare, potentially aggressive
      odontogenic epithelial tumor with tendency for recurrence. It was first described
      as a clinicopathological entity in 1985 and to date only 73 cases has been
      reported in English literature. A case of CCOC in 64-year-old male patient in
      mandibular anterior region is presented which when recurred in soft tissue 5
      years after wide surgical resection of mandible, revealed a biphasic pattern as
      against monophasic pattern of primary neoplasm and was unusually associated with
      primary squamous cell carcinoma, suggestive of hybrid tumor. 

PMID- 25949005
TI  - Mandibular metastasis in a patient with undiscovered synchronous thyroid and
      prostate cancer: A diagnostic dilemma.
AB  - BACKGROUND: Mandibular metastasis as the first manifestation of undiscovered
      synchronous double primary cancers is extremely rare, so, it is presented in the
      current study. CASE HISTORY: This study reports a 73-year-old man, complaining of
      a painful mass in the mandible. After history taking, physical examination and
      panoramic radiographic evaluation; an incisional biopsy was performed
      intraorally. Histological studies revealed a metastatic tumor of epithelial
      origin with nonspecific primary site. During metastatic workup of the patient, it
      was accidentally found that three organs including prostate, lung and thyroid
      were involved with cancer. Using immunohistochemical study (prostate-specific
      antigen (PSA), thyroid transcription factor 1 (TTF-1) and thyroglobulin), a final
      diagnosis of thyroid carcinoma metastasis to the mandible was established.
      DISCUSSION: This case report showed that the practitioners should always maintain
      a high index of suspicion to the possibility that a patient with an orofacial
      metastatic lesion may have two or more synchronous primary cancers.

PMID- 25949006
TI  - Primary leiomyosarcoma of the maxilla: An investigative loom-report of a
      challenging case and review of literature.
AB  - Leiomyosarcoma (LMS) is a malignant neoplasm composed of cells showing distinct
      smooth muscle features. Majority of the tumors are located in the
      retroperitoneum, including the pelvis and the uterus but are rare in the oral and
      pharyngeal region. Intraorally, they are present as painless, lobulated, fixed
      masses of the submucosal tissues in middle-aged or older individuals. Lesions are
      usually slow growing and are less than 2 cm in diameter at the time of diagnosis.
      Here we report the clinico-pathological findings of a case of primary LMS of the
      maxilla in 63-year-old male patient with an emphasis on the judicious use of
      ancillary diagnostic modalities to arrive at a definitive diagnosis. 

PMID- 25949007
TI  - Fatal rhino-orbito-cerebral mucormycosis in a healthy individual.
AB  - Rhino-orbital-cerebral zygomycosis is a potentially lethal, opportunistic, fungal
      infection with protean manifestations, rapid progression, unpredictable course
      and high mortality. It is associated with angioinvasion and infarction, usually
      observed in diabetic ketoacidosis, immuno-compromised states and rarely reported
      in an apparently normal host. We present a case of an18-year-old patient with a
      chronic, painful, non healing ulcer with necrotic margins over the right side of
      the face which extended to both orbits involving eyes within a period of 1.5
      month. Later he developed severe headache, decreased vision, inability to speak,
      seizures and status epilepticus with fatal outcome. Awareness of its occurrence
      in normal patients with prompt diagnosis and appropriate management may improve
      the outcome and decrease mortality. 

PMID- 25949008
TI  - Chondroblastic osteosarcoma.
AB  - The purpose of this paper is to report a case of chondroblastic osteosarcoma in
      the region of the maxilla, with 5 months of evolution. The term osteosarcoma
      refers to a heterogeneous group of malignancies with bone formation or
      mesenchymal tissue with histopathological evidence of osteogenic differentiation.
      The pattern of chondroblastic osteosarcoma represents 25% of all reported cases
      of this neoplasm. Its histopathological diagnosis is based on the predominance of
      a chondroid matrix formed in the midst of neoplastic cells. A woman patient, 27
      year old, melanoderm, presented on extraoral exam with facial asymmetry caused by
      the a swelling in the premaxillary region with upper lip protrusion. Intraoral
      exam showed a maxillary tumefaction with involvement of the vestibular and
      palatine regions. The computerized tomography (CT) analysis exhibited a
      radiolucent mass with dispersed areas of radiopacity, with poorly defined and
      indistinct peripheral edges. The patient was subjected to incisional biopsy and
      histopathological examination showed the presence of a malignant neoplasm of
      mesenchymal origin characterized by the presence of irregular bone trabeculae
      dispersed among mildly atypical chondroblastic cells. The World Health
      Organization (WHO) recognizes several variants that differ in location, clinical
      behavior and degree of cellular atypia. The conventional or classical
      osteosarcoma is the most frequent variant, which develops within the medullary
      bone. This report illustrates the rapid evolution of one of the histological
      variants of osteosarcoma. 

PMID- 25949009
TI  - Teratoid cyst of the oral cavity: A rare entity.
AB  - The teratoid cyst is a rare variant of the dermoid cyst which seldom occurs in
      the oral cavity. If seen, they generally present as slow growing cysts of the
      floor of mouth, reported commonly in the 2(nd) and 3(rd) decade of life in males.
      Histopathologically, dermoid cyst is classified as epidermoid cyst, true dermoid
      cyst and teratoid cyst depending on the presence of adnexal structures and
      derivatives of all three germ layers. Herewith we report a rare case of teratoid
      cyst of the floor of the mouth, in a 2-year-old female child, which was present
      since birth. 

PMID- 25949010
TI  - Myoepithelial cell carcinoma of the oral cavity: A case report and review of
      literature.
AB  - Myoepithelial carcinoma (MC) is a malignant salivary gland neoplasm whose tumor
      cells demonstrate cytologic differentiation toward myoepithelial cells and lack
      ductal or acinar differentiation. It is a relatively rare tumor and many a times
      remains undiagnosed because of histopathological heterogeneity. It represents
      about 0.4-0.6% of all salivary gland tumors and 1.2-1.5% of carcinomas. It occurs
      predominantly in the parotid gland with a mean age of presentation being 55 years
      (range 14-86) with no sex predilection. MC appears to be a low grade malignancy
      when arising in a pleomorphic adenoma, but tends to be more aggressive and has a
      higher metastatic potential when arising de novo. The clinical behavior of MC is
      variable and there are no pathologic features that correlate with patients'
      outcome. Most tumors that display marked cytologic atypia, high mitotic activity
      and necrosis tend to behave aggressively. The current case is of a 42-year-old
      male with recurrent tumor mass in the mandibular right posterior region. The
      purpose of this article was to describe the clinicopathological and
      immunohistochemical features of intraoral MC and to discuss review of literature
      of this rare tumor. 

PMID- 25949011
TI  - Osteocartilaginous choristoma of buccal mucosa: A rare entity.

PMID- 25949013
TI  - Solitary bone cysts-A rare occurrence with bilaterally symmetrical presentation.
AB  - Solitary bone cysts (SBCs) are bone cavities that lack a true epithelial lining.
      They are more commonly seen during the first 2decades of age.Very few cases have
      been reported over 40 years of age.SBCs are usually discovered as an accidental
      coexisting finding during a routine radiologic examination or during another
      unrelated dental complaint. They present as a unilocular or multilocular
      radiolucent lesion associated with vital teeth with mild or no cortical
      expansion. Bilateral presentation is however very rare. We present a case of 52
      year-old female patient with bilateral presentation of SBCs. 

PMID- 25949012
TI  - Chronic suppurative osteomyelitis of posterior maxilla: A rare presentation.
AB  - Thin cortical bone rich in vascularity makes the maxilla scarcely vulnerable to
      osteomyelitis as compared to mandible. Moreover, the introduction of newer
      antibiotics, understanding of pathogenesis and improved medical support lead to
      reduction in incidence of osteomyelitis. Local factors like continuous
      irritation, smoking and suppressed immune system contributes to the occurrence of
      suppurative osteomyelitis. We hereby, report an exceptional case of chronic
      suppurative osteomyelitis of posterior maxilla in a 42-year-old healthy male who
      was managed successfully by combination of antibiotics, surgical sequestrectomy
      and debridement. 

PMID- 25949014
TI  - Bridging the generation gap-dilemmas of a cosmetic surgeon.

PMID- 25949015
TI  - Shifting paradigm in laser tattoo removal.

PMID- 25949016
TI  - Laser-tissue interaction in tattoo removal by q-switched lasers.
AB  - Q-switched (QS) lasers are widely considered the gold standard for tattoo
      removal, with excellent clinical results, impressive predictability, and a good
      safety profile. The generation of giant pulses by the method of Q-switching is
      responsible for the unique laser-tissue interaction that is seen in tattoo
      removal by QS lasers. The QS lasers work by impaction and dissolution of the
      tattoo pigments. Mechanical fragmentation of the tattoo pigments encased in
      intracellular lamellated organelles followed by their phagocytosis by macrophages
      is thought to be the major event in the clearance of pigments by QS lasers. A few
      novel techniques have been tried in recent times to hasten the clearance of
      tattoo pigments. 

PMID- 25949017
TI  - Laser tattoo removal: a clinical update.
AB  - Techniques for tattoo removal have evolved significantly over the years. The
      commonly used Quality-switched (QS) ruby, alexandrite, and Nd:YAG lasers are the
      traditional workhorses for tattoo removal. Newer strategies using combination
      laser treatments, multi-pass treatments, and picosecond lasers offer promising
      results. The tattoo color and skin type of the patient are important
      considerations when choosing the appropriate laser. Standard protocols can be
      developed for the effective and safe treatment of tattoos. 

PMID- 25949018
TI  - Optimising laser tattoo removal.
AB  - Lasers are the standard modality for tattoo removal. Though there are various
      factors that determine the results, we have divided them into three logical
      headings, laser dependant factors such as type of laser and beam modifications,
      tattoo dependent factors like size and depth, colour of pigment and lastly host
      dependent factors, which includes primarily the presence of a robust immune
      response. Modifications in the existing techniques may help in better clinical
      outcome with minimal risk of complications. This article provides an insight into
      some of these techniques along with a detailed account of the factors involved in
      tattoo removal. 

PMID- 25949019
TI  - Newer trends in laser tattoo removal.
AB  - Q switched lasers are the current gold standard for laser tattoo removal. Though
      these systems are generally quite effective in clearing tattoos & have an
      established safety record, certain limitations exist while following the standard
      protocol. To overcome these limitation newer techniques such as multipass method,
      combination treatments with chemical agent and other laser have been introduced.
      These methods help in faster, less painful and complication free tattoo removal. 

PMID- 25949020
TI  - Complications of Tattoos and Tattoo Removal: Stop and Think Before you ink.
AB  - Tattooing is a process of implantation of permanent pigment granules in the skin.
      Tattoos can be decorative, medical or accidental. There has been a exponential
      increase in decorative tattooing as a body art in teenagers and young adults.
      Unfortunately there are no legislations to promote safe tattooing, hence
      complications are quite common. Superficial and deep local infections, systemic
      infections, allergic reactions, photodermatitis, granulomatous reactions and
      lichenoid reactions may occur. Skin diseases localised on the tattooed area, such
      as eczema, psoriasis, lichen planus, and morphea can be occasionally seen. When
      used as a camouflage technique, colour mismatch and patient dissatisfaction are
      common complications. On the other hand, regrets after a tattoo are also seen and
      requests for tattoo removal are rising. Laser tattoo removal using Q-switched
      lasers are the safest; however, complications can occur. Acute complications
      include pain, blistering, crusting and pinpoint hemorrhage. Among the delayed
      complications pigmentary changes, hypopigmentation and hyperpigmentation,
      paradoxical darkening of cosmetic tattoos and allergic reactions can be seen.
      Another common complication is the presence of residual pigmentation or ghost
      images. Scarring and textural changes are potential irreversible complications.
      In addition, tattoo removal can be a prolonged tedious procedure, particularly
      with professional tattoos, which are difficult to erase as compared to amateur
      tattoos. Hence the adage, stop and think before you ink holds very much true in
      the present scenario. 

PMID- 25949021
TI  - Efficacy of 15% trichloroacetic Acid and 50% glycolic Acid peel in the treatment
      of frictional melanosis: a comparative study.
AB  - BACKGROUND: Frictional dermal melanosis is aesthetically displeasing. Various
      modalities ranging from depigmenting agents to lasers have been tried but it
      continues to be a difficult problem to treat. OBJECTIVE: To study and compare the
      efficacy of 15% trichloroacetic acid (TCA) and 50% glycolic acid in the treatment
      of frictional melanosis of the forearm. MATERIALS AND METHODS: 40 patients of
      frictional melanosis of the forearm were included in the study. Patients were
      randomly divided into two equal groups A and B. Pre-peel priming was carried out
      with 12% glycolic acid and sunscreen for 2 weeks. Group A was treated with
      trichloroacetic acid (TCA-15%) peel and Group B with glycolic acid (GA-50%) peel.
      Four peels were done one every 15 days. Clinical photographs were taken to assess
      the response. Response to therapy was evaluated by both objective and subjective
      methods. The patients were followed up for 3 months after the last peel to note
      any relapse. RESULTS: Both TCA and glycolic acid peels were effective in
      frictional melanosis. TCA showed better response compared to glycolic acid at the
      end of the treatment, both by subjective and objective methods. However, this
      difference was not statistically significant (P > 0.05). No permanent side
      effects were seen in any of the treated patients and the improvement was
      sustained without any relapse at 3 months. CONCLUSION: Chemical peeling with both
      tricholoroacetic acid (15%) and glycolic acid (50%) is safe and effective for the
      treatment of frictional dermal melanosis. Tricholoroacetic acid was found to be
      marginally superior to glycolic acid.

PMID- 25949022
TI  - Efficacy of Modified Jessner's Peel and 20% TCA Versus 20% TCA Peel Alone for the
      Treatment of Acne Scars.
AB  - INTRODUCTION: There is a paucity of studies on the use of chemical peels for acne
      scars among the Asian population. A trichloroacetic acid (TCA) and Jessner's
      combination chemical peel, originally described by Monheit, is said to be better
      than a TCA peel alone. AIMS: The aim of the study was to compare the efficacy of
      20% TCA and Jessner's solution versus 20% TCA alone for the treatment of acne
      scars. MATERIALS AND METHODS: : The patients were divided into two groups of 25
      patients each. Chemical peeling was done in both the groups. In Group I, chemical
      peeling with Jessner's peel followed by 20% TCA was done and in Group II patients
      chemical peeling with 20% TCA peel alone was done. RESULTS: In Group I (Jessner's
      peel and 20% TCA), mild improvement of acne scars was seen in 8% cases, moderate
      improvement in 32% cases and marked improvement of acne scars was seen in 60%
      patients. In Group II (20% TCA), mild improvement of acne scars was seen in 32%
      cases, moderate improvement in 40% cases and marked improvement of acne scars was
      seen in 28% patients. But, the difference in improvement of acne scars was not
      statistically significant in both the groups (P value > 0.05).

PMID- 25949023
TI  - Ultrapulse carbon dioxide laser ablation of xanthelasma palpebrarum: a case
      series.
AB  - CONTEXT: Xanthelasma palpebrarum is the most common form of xanthomas. Albeit a
      benign entity, it is cosmetically disturbing and a frequently recurring
      dermatologic referral. Although the classical treatment option remains surgical
      excision, alternatively, chemical cauterization, cryosurgery and
      electrofulguration have all been tried in the past with mixed results. The use of
      laser systems such as carbon dioxide laser, Erb:YAG laser, Q-switched Nd:YAG
      laser, diode laser, pulsed dye laser and KTP laser have become popular in the
      treatment of these lesions. Recent literature suggests minimal pigmentary changes
      and scarring with the use of ultrapulse carbon dioxide laser treatment of these
      lesions. AIM: To study and evaluate the effectiveness of ultrapulse carbon
      dioxide laser ablation for treatment of xanthelasma palpebrarum. MATERIALS AND
      METHODS: 10 patients presenting with bilateral xanthelasma palpebrarum, new and
      with recurrence were studied for results after a single treatment with ultrapulse
      carbon dioxide laser (10,600 nm; 100-200 Hz; 200-400 MUsec). The follow-up time
      was 9 months. RESULTS: All lesions were treatable with a single-laser treatment
      session. Two patients (20%) developed recurrence during the follow-up period.
      Side effects included post inflammatory hyperpigmentation in two patients (20%),
      but no visible scarring was observed. CONCLUSIONS: The ultrapulse carbon dioxide
      laser is an effective and safe therapeutic alternative in treatment of
      xanthelasma palpebrarum.

PMID- 25949024
TI  - External tissue expansion for difficult wounds using a simple cost effective
      technique.
AB  - OBJECTIVE: To study and discuss role of external tissue expansion and wound
      closure (ETEWC) technique using hooks and rubber bands. MATERIALS AND METHODS:
      The present study is a retrospective analysis of nine cases of wounds of
      different aetiology where ETEWC technique was applied using hooks and rubber
      bands. RESULTS: All the wounds in the study healed completely without split
      thickness skin graft (SSG) or flap. CONCLUSION: ETEWC technique using hooks and
      rubber bands is a cost-effective technique which can be used for wound closure
      without SSG or flap.

PMID- 25949025
TI  - Repair of minor true hare lip using v-y plasty: how I do it.
AB  - BACKGROUND: Minor true hare lip is rare central midline deficiency of the upper
      lip. There are multiple techniques but little consensus on the preferred surgical
      technique. MATERIALS AND METHODS: A transoral approach for repair using mucosal V
      Y plasty is described by employing a vertical inverted V incision. RESULT: The
      contour of the free labial border immediately improves with avoidance of skin
      scar. CONCLUSIONS: The midline cleft lip notch or minor true (hare lip) midline
      clefts can be effectively treated by mucosal lengthening using a V-Y plasty.
      Moreover, the ability to augment the tubercle with mucosa through a VY plasty is
      simple and easy.

PMID- 25949026
TI  - Cosmetic surgery in teenagers: to do or not to do.
AB  - The media makes it out to be a big story that teens are getting cosmetic surgery
      in larger numbers than ever. However, this is far from the truth. Yearly data, is
      increasingly showing a reduction in the percentage, as well as absolute numbers
      of these surgeries. Only, very essential surgery should be done for teenagers.
      The consult should be done in the presence of a parent, and even if the teen is
      above legal consenting age, parental supervision is still needed. A cooling off
      period, informed consent under parental supervision, and a time to rethink is
      essential. If a problem is severe enough to cause psychological problems, a
      psychologist can help in arriving at a decision. 

PMID- 25949027
TI  - An unusual case of desmoplastic malignant melanoma.
AB  - Desmoplastic malignant melanoma is a rare variant of spindle cell melanoma,
      commonly seen in older adults, on sun-exposed areas. It accounts for 1-4% of all
      cases of cutaneous melanoma. The common location of the desmoplastic melanoma is
      the head and neck region, whereas, other sites are less common. Regional lymph
      node involvement is reported in 0 to 13.7% of the cases, which is less frequent
      than other cutaneous melanomas. A 75-year-old male presented with an
      ulceroproliferative growth on the left foot that was diagnosed as desmoplastic
      melanoma with regional lymph node metastasis and in transit metastasis, with
      extensive pulmonary metastasis. 

PMID- 25949028
TI  - Aesthetic management of gum hyperpigmentation by a simple technique.

PMID- 25949029
TI  - Giant scrotal lymphoedema.

PMID- 25949030
TI  - Persistence of hyaluronic Acid filler for subcutaneous atrophy in a case of
      circumscribed scleroderma.

PMID- 25949031
TI  - Elective tongue piercing: fad with fallout.

PMID- 25949032
TI  - Second degree skin burn with garlic and table salt.

PMID- 25949033
TI  - Erratum: Primary Bilateral Extramammary Paget's Disease of the Axillae: Another
      Case of this Strange Disease: Erratum.
AB  - [This corrects the article on p. 131 in vol. 7, PMID: 25136219.]. 

PMID- 25949034
TI  - Erratum: Split Face Comparative Study of Microneedling with PRP Versus
      Microneedling with Vitamin C in Treating Atrophic Post Acne Scars: Erratum.
AB  - [This corrects the article on p. 209 in vol. 7, PMID: 25722599.]. 

PMID- 25949035
TI  - What's new in emergencies, trauma and shock? Need for a greater debate on
      "Incidental cranial computed tomography findings".

PMID- 25949036
TI  - Incidental cranial CT findings in head injury patients in a Nigerian tertiary
      hospital.
AB  - BACKGROUND: Incidental findings on computed tomography (CT) scans are
      occasionally noted in patients presenting with head injury. Since it can be
      assumed that head injured patients are of normal health status before the
      accident, these findings may be a representation of their frequency in the
      general population. Our aim was to determine the prevalence of such incidental
      findings among head injured patients in Nigeria's foremost center of clinical
      neurosciences. MATERIALS AND METHODS: We conducted a retrospective review of CT
      scan images of 591 consecutive eligible patients over a 5-year period (2006-2010)
      to identify incidental findings. The images were evaluated by consensus agreement
      of two radiologists. Associations with gender and age were explored using
      appropriate statistical tests with an alpha level of 0.05. RESULTS: The mean
      patient age was 34.6 +/- 21.2 years, and male to female ratio was 3.2: 1.
      Incidental findings were noted in 503/591 (85.1 %) of the scans. Intracranial
      calcification was the commonest finding occurring in 61.8% of patients. Over 90%
      of the findings were benign. Compared with older ones, patients under the age of
      60 were less likely, (P < 0.001), to have incidental findings. CONCLUSION:
      Although the majority of incidental findings in this African cohort of head
      injury patients are benign some clinically significant lesions were detectable.
      It is therefore recommended that such findings be adequately described in the
      radiological reports for proper counseling and follow-up.

PMID- 25949037
TI  - Management and outcomes of traumatic hemothorax in children.
AB  - BACKGROUND: Adult guidelines for the management of traumatic hemothorax are well
      established; however, there have been no similar studies conducted in the
      pediatric population. The purpose of our study was to assess the management and
      outcomes of children with traumatic hemothorax. MATERIALS AND METHODS: Following
      Institutional Review Board approval, we conducted a retrospective cross-sectional
      study of all trauma patients diagnosed with a hemothorax at a Level-1 pediatric
      trauma center from 2007 to 2012. RESULTS: Forty-six children with hemothorax were
      identified, 23 from blunt mechanism and 23 from penetrating mechanism. The
      majority of children injured by penetrating mechanisms were treated with tube
      thoracostomy while the majority of blunt injury patients were observed (91.3% vs.
      30.4% tube thoracostomy, penetrating vs. blunt, P = 0.00002). Among patients
      suffering from blunt mechanism, children who were managed with chest tubes had a
      greater volume of hemothorax than those who were observed. All children who were
      observed underwent serial chest radiographs demonstrating no progression and
      required no delayed procedures. Children with a hemothorax identified only by
      computed tomography, after negative plain radiograph, did not require
      intervention. No child developed a delayed empyema or fibrothorax. CONCLUSION:
      The data suggest that a small-volume hemothorax resulting from blunt mechanism
      may be safely observed without mandatory tube thoracostomy and with overall low
      complication rates.

PMID- 25949038
TI  - Clinical manifestations that predict abnormal brain computed tomography (CT) in
      children with minor head injury.
AB  - BACKGROUND: Computed tomography (CT) used in pediatric pediatrics brain injury
      (TBI) to ascertain neurological manifestations. Nevertheless, this practice is
      associated with adverse effects. Reports in the literature suggest incidents of
      morbidity and mortality in children due to exposure to radiation. Hence, it is
      found imperative to search for a reliable alternative. OBJECTIVES: The aim of
      this study is to find a reliable clinical alternative to detect an intracranial
      injury without resorting to the CT. MATERIALS AND METHODS: Retrospective cross
      sectional study was undertaken in patients (1-14 years) with blunt head injury
      and having a Glasgow Coma Scale (GCS) of 13-15 who had CT performed on them.
      Using statistical analysis, the correlation between clinical examination and
      positive CT manifestation is analyzed for different age-groups and various
      mechanisms of injury. RESULTS: No statistically significant association between
      parameteres such as Loss of Consciousness, 'fall' as mechanism of injury, motor
      vehicle accidents (MVA), more than two discrete episodes of vomiting and the CT
      finding of intracranial injury could be noted. Analyzed data have led to believe
      that GCS of 13 at presentation is the only important clinical predictor of
      intracranial injury. CONCLUSION: Retrospective data, small sample size and
      limited number of factors for assessing clinical manifestation might present
      constraints on the predictive rule that was derived from this review. Such
      limitations notwithstanding, the decision to determine which patients should
      undergo neuroimaging is encouraged to be based on clinical judgments. Further
      analysis with higher sample sizes may be required to authenticate and validate
      findings.

PMID- 25949039
TI  - Increased mean arterial pressure goals after spinal cord injury and functional
      outcome.
AB  - INTRODUCTION: Acute spinal cord injury (SCI) is often treated with induced
      hypertension to enhance spinal cord perfusion. The optimal mean arterial pressure
      (MAP) likely varies between patients. Arbitrary goals are often set, frequently
      requiring vasopressors to achieve, with no clear evidence supporting this
      practice. We hypothesize that increased MAP goals and episodes of relative
      hypotension do not affect hospital outcome. MATERIALS AND METHODS: All cervical
      and thoracic SCI patients treated at a level one trauma and regional SCI center
      over at 2.5-year period were retrospectively reviewed. Lowest and average hourly
      MAP was recorded for the first 72 h of hospitalization, allowing for
      quantification of mean MAP and the total number of episodic relative hypotensive
      events. These data were further compared to daily American spinal injury
      association motor score (AMS), which was used to determine the severity of SCI
      and improvement/decline during hospitalization. Patient's data were finally
      analyzed at theoretic MAP set points. RESULTS: One hundred and five patients had
      complete data during the study period. At higher theoretic MAP set points (85 and
      90), increased number of relative hypotensive episodes correlated with lower
      admission AMS (85 mmHg: <10 episodes, AMS 66.2; >50 episodes, 22.0; P < 0.001)
      and the need for vasopressors (P < 0.03) but showed no statistical change in AMS
      by hospital discharge. The need for vasopressors correlated with the number of
      hypotensive episodes and inversely related to admission AMS at all theoretic MAP
      goal set points but was not correlated with the change in AMS during the
      hospitalization. CONCLUSIONS: The frequency of relative hypotension and the need
      for vasopressors are progressively related to more severe SCI, as denoted by
      lower admission AMS. However, episodes of hypotension and the need for
      vasopressors did not affect the change in AMS during the acute hospitalization,
      regardless of theoretic MAP goal set-point. Arbitrarily elevated MAP goals may
      not be efficacious.

PMID- 25949040
TI  - Intubations and airway management: An overview of Hassles through third
      millennium.
AB  - BACKGROUND: The placement of a tube into a patient's trachea "the intubation" as
      we call is not as simple as it looks. It is a very tricky and tedious maneuver
      that entails skills to assess and perform. Nevertheless, often this is left to
      the chores of inefficient hands due to a paucity of the availability of experts.
      They seldom are able to complete the task and often wind up calling the attention
      of the unit. The present review is an attempt to describe the need to undertake
      intubation, the procedures and techniques, the complications, including morbidity
      and mortality and airway management. This overview includes explicit descriptions
      of the difficult airway which represents multifaceted interface amid patient
      factors, clinical setting, and skills of the practitioner. MATERIALS AND METHODS:
      To accomplish the target, peer-reviewed English language articles published
      during third millennium up to 2013 were selected from Pub Med, Pub Med Central,
      Science Direct, Up-to-date, Med Line, comprehensive databases, Cochrane library,
      and the Internet (Google, Yahoo). REVIEW OF LITERATURE: The review constituted a
      systematic search of literature on the requirements that necessitate the practice
      of intubation, different techniques that facilitate easy conduct of procedure,
      the complications, including, morbidity and mortality, and the airway management.
      CONCLUSION: Recording every single detail has been beyond the scope of this
      review, however; some aspects have been wrapped up in nutshell. Some areas of the
      review are too basic which the medics are well aware of and knowledgeable.
      Nevertheless, these are difficult to be dispensed with in consideration of their
      source to the awareness of a common man and a great majority of the patients.

PMID- 25949041
TI  - A case report of bittern intoxication.
AB  - Bittern is made from marine water after extraction of salt, and its major
      components include magnesium chloride, magnesium sulfate, potassium chloride,
      sodium chloride and magnesium bromide. For a long time, it has been used as the
      main ingredient of tofu coagulant and chemical weapons. A 73-year-old woman
      arrived to the emergency department after a suicide attempt by drinking an
      unknown amount bittern. She complained of dizziness, general weakness, and
      altered mental state (Glasgow Coma Scale (GCS) 13/15). The brain computed
      tomography (CT) and magnetic resonance imaging (MRI) showed no abnormality. But
      blood chemistry showed hypermagnesemia ([Mg(2+)] 7.8 mEq/L) and hypernatremia
      ([Na(+)] 149 mEq/L). Electrocardiograph showed QT prolongation of 0.482 s.
      Electrolyte imbalances were corrected following adequate fluid therapy and
      injection of calcium gluconate. The patient recovered/was subsequently discharged
      without any complications. Electrolyte imbalances are a common presentation
      following bittern poisoning. Severe side effects like respiratory depression,
      hypotension, arrhythmia, bradycardia, and cardiac arrest can also occur. Patients
      will require immediate fluid therapy and correction of electrolyte imbalances.
      The symptoms vary depending on the electrolyte levels. It is mandatory to closely
      monitor the electrolyte levels and electrocardiograph in these patients. 

PMID- 25949042
TI  - Acute myocardial infarction and coronary artery dissection following rugby
      related blunt chest trauma in France.
AB  - Coronary artery (CA) dissection following blunt chest trauma is a life
      threatening and rare event. Its occurrence in the setting of a contact sport like
      rugby is even less common. We report on two cases of young adult presenting with
      segment elevation myocardial infarction related to CA dissection following rugby
      game. Both were successfully treated with stent implantation. We discuss the
      mechanism, diagnosis, and optimal management of blunt chest trauma-induced CA
      dissection. 

PMID- 25949043
TI  - Low pressure traumatic epidural hematoma in a child with a prior hemispherectomy:
      Case report.
AB  - A 21/2-year-old male child with a prior history of a left anatomic
      hemispherectomy to treat refractory epilepsy fell down two steps, striking his
      head on the ipsilateral side of the hemispherectomy. He presented with non
      consolable crying and emesis. CT scan of the head demonstrated a left frontal
      epidural hematoma beneath the site of his prior craniectomy. The patient was
      initially treated by close observation. However, due to an increase in the
      hematoma from 29.5 to 49.3 ml over a 12-hour period along with the patient's lack
      of clinical improvement, surgical evacuation was performed. Intraoperatively, the
      source of the hemorrhage was found to be the skull fracture. Postoperatively, he
      returned to his neurologic baseline and was discharged home on postoperative day
      3. 

PMID- 25949044
TI  - Accidental oropharyngeal impalement injury in children: A report of two cases.
AB  - Impalement injuries in children may be deeper and more complicated than
      anticipated. We experienced two cases of accidental impalement injuries, one was
      through the oral cavity and the other was to the neck. We review these cases and
      the management of these types of injuries. CASE SERIES: In case 1, a 20-month-old
      girl fell from the table with a toothbrush in her mouth. She was conscious,
      without any apparent neurologic or vascular injuries. Examination revealed a 2 mm
      laceration with a small hematoma in the right posterior pharyngeal wall. Contrast
      enhanced computed tomography (CECT) revealed an air tract penetrating between the
      mandibular ramus and cervical vertebrae, passing by the carotid sheath, and
      reaching under the skin of the right posterior neck. Surgical emphysema was
      extended from the pharynx to the mediastinum. In case 2, a 3-year-old girl fell
      while holding a pencil. Physical examination revealed a 5 mm laceration in front
      of her right ear lobe accompanied by a small hematoma. Her facial movement was
      asymmetric, and she could not close her right eye. CECT showed swelling of the
      right parotid gland with heterogeneous enhancement and free air just in front of
      the right carotid sheath, which suggested the object penetrated through the
      parotid gland. A diagnosis of peripheral facial nerve injury was made. Physicians
      need to be aware of the potentially life-threatening complications of impalement
      injuries in children, as well as the specific complications related to proximity
      to specific anatomic structures.

PMID- 25949045
TI  - Retropharyngeal calcific tendinitis: Report of two cases.

PMID- 25949046
TI  - Significance of pneumorrhachis detected by single-pass whole-body computed
      tomography in patients with trauma.

PMID- 25949047
TI  - Hints in electrocardiography for coming myocardial infarction.

PMID- 25949048
TI  - Suicidal poisoning with cypermethrin: A clinical dilemma in the emergency
      department.

PMID- 25949049
TI  - Successful treatment of a penetrating pulmonary artery injury caused by a
      Japanese sword in a patient transported by a physician-staffed helicopter.

PMID- 25949050
TI  - Looking at four corners.

PMID- 25949051
TI  - Challenges in tuberculosis diagnosis and management: recommendations of the
      expert panel.

PMID- 25949052
TI  - Efficiency assessment of immunochromatographic strip test for the diagnosis of
      alpha-thalassemia-1 carriers.
AB  - CONTEXT: The prevention and control of thalassemia in Thailand focus on the
      appropriate diagnosis with a simple, cheap, and practical tool for any staff to
      use. AIMS: (1) To screen alpha-thalassemia-1 carriers among pregnant women and
      spouses by immunochromatographic (IC) strip test and one tube osmotic fragility
      test (OFT) and (2) to evaluate the accuracy of both screening methods. SETTING
      AND DESIGN: Cross-sectional study for 6 months duration from January to June 2013
      at Kudjab Hospital located in Udonthani Province, Thailand. SUBJECTS AND METHODS:
      Pregnant women and spouses attending the antenatal care clinic joined the study
      for blood sample collection (n = 414). The specimens were then taken for
      screening by osmotic fragility and IC strip test to specify alpha-thalassemia
      carriers. Another set of the specimens was sent for testing using hemoglobin (Hb)
      typing for thalassemia and abnormal Hb carriers and using multiplex polymerase
      chain reaction for alpha-thalassemia-1 carriers diagnosis as a gold standard.
      RESULTS: There were 27 cases found as positive for alpha-thalassemia including
      alpha-thalassemia-1 carriers, South East Asian type, alpha-thalassemia-1
      carriers, Thai deletion type, HbH and Hb constant spring, which were 18, 2, 3,
      and 2 cases, respectively. The sensitivity, specificity, positive predictive
      value, negative predictive value, and accuracy of IC strip test were 92.6%,
      95.1%, 56.8%, 99.4%, and 94.9%, respectively, which were higher than those of
      OFT. CONCLUSIONS: Accuracy of IC strip test was better than those of OFT. IC
      strip test may probably be very helpful in a massive thalassemia screening
      program.

PMID- 25949053
TI  - A Leap above Friedewald Formula for Calculation of Low-Density Lipoprotein
      Cholesterol.
AB  - PURPOSE: The purpose was to compare the different calculated methods of low
      density lipoprotein cholesterol (LDL-C) estimation and to determine which of them
      correlate best with the direct method. MATERIALS AND METHODS: The records of 480
      samples for lipid profile were analyzed. Apart from the direct method, LDL-C was
      calculated by Friedewald low-density lipoprotein cholesterol method (F-LDL-C),
      modified Friedewald low-density lipoprotein cholesterol method (MF-LDL-C), and
      Anandaraja low-density lipoprotein cholesterol method (A-LDL-C). Paired t-test
      and Pearson correlation were evaluated between the different methods. Degree of
      agreement between the calculated methods and direct method was detected by Bland
      Altman graphical plots. RESULTS: A strong correlation was found between all
      calculated LDL-C methods and direct low-density lipoprotein cholesterol method (D
      LDL-C) assay, that is, F-LDL-C versus D-LDL-C = 0.94; A-LDL-C versus D-LDL-C =
      0.93 and MF-LDL-C versus D-LDL-C = 0.95. No statistically significant difference
      was found between D-LDL-C and MF-LDL-C. Bland-Altman plot for MF-LDL-C showed
      minimal negative bias. CONCLUSIONS: The study pointed out that MF-LDL-C
      correlated maximally with D-LDL-C estimation at all levels of triglycerides and
      MF-LDL-C can be used in place of D-LDL-C when the direct method cannot be
      afforded.

PMID- 25949054
TI  - Performance of a 27 kDa Fasciola hepatica Antigen in the Diagnosis of Human
      Fascioliasis.
AB  - BACKGROUND: Serological diagnosis, based on antigenic fractions of the parasite
      can be used for the early diagnosis of human fascioliasis. The current study
      aimed to evaluate the efficacy of a 27 kDa immunodominant antigen of Fasciola
      hepatica adult worms, in an indirect enzyme-linked immunosorbent assay (ELISA)
      system for serological diagnosis of human fascioliasis. MATERIALS AND METHODS:
      The immunodiagnosis of human fascioliasis, using a 27 kDa immunodominant antigen,
      purified from F. hepatica somatic antigens (SAs), was evaluated by Western
      blotting and ELISA with sera samples of human fascioliasis patients, healthy
      controls and patients with other parasitic infections. RESULTS: Using western
      blotting, from 12 sera of fascioliasis patients, 11 sera (91.6%) detected the 27
      kDa subunit. None of 30 samples from healthy controls or 32 sera from
      nonfascioliasis patients reacted with the 27 kDa antigen. Accordingly,
      sensitivity and specificity of the system was found to be 91.6% and 100%,
      respectively. The 27 kDa antigen was purified from the SAs and was used in an
      indirect ELISA system. Of 15 sera of fascioliasis patients, all (100%) were found
      to be positive by ELISA whereas only 4 cases (6.25%) of nonfascioliasis patients
      or healthy controls were false-positive by this system. Accordingly, the
      sensitivity and specificity of the test were 100% and 93.6%, respectively.
      CONCLUSION: Findings of this study demonstrated that both Western blotting and
      the indirect ELISA, based on the 27 kDa subunit of F. hepatica SA, are reliable
      methods for serodiagnosis of human fascioliasis.

PMID- 25949055
TI  - Role of needle aspiration in diagnosis and management of suppurative bacille
      calmette-guerin adenitis: an institutional study of 30 cases.
AB  - CONTEXT: Regional lymphadenitis is the most common complication of bacille
      Calmette-Guerin (BCG) vaccination. Most of the BCG lymphadenitis cases are
      nonsuppurative, but some suppurate and follow abscess formation, rupture,
      ulceration and cicatrization. Needle aspiration is the rapid, safe and cost
      effective method for diagnosis as well as management of suppurative BCG adenitis.
      AIMS: The aims of the present study were to assess the clinical and cytological
      spectrum of BCG lymphadenitis and to evaluate the role of needle aspiration in
      the management of suppurative BCG lymphadenitis. SETTINGS AND DESIGN: We have
      approached every cases of ipsilateral axillary lymphadenopathy having history of
      BCG vaccination. We designed to aspirate the suppurative axillary lymph nodes and
      follow-up of nonsuppurative cases. SUBJECTS AND METHODS: 30 cases of BCG adenitis
      were studied during a period of 2 years. 12 cases of suppurative lymphadenitis
      were approached by needle aspiration and cytologically evaluated, and all the
      cases were followed-up for 12 weeks after diagnosis. Anti-tubercular drugs were
      not applied, and surgical excision was reserved for nonhealing lesions.
      STATISTICAL ANALYSIS USED: Data tables. RESULTS: Ipsilateral axillary lymph nodes
      were commonest site and none had constitutional symptoms. Acid-fast bacilli were
      detected in 11 (91.67%) cases of suppurative BCG lymphadenitis. On follow-up all
      nonsuppurative adenitis were resolved spontaneously, and 8 suppurative
      lymphadenitis cases were resolved after 4 weeks of needle aspiration. Four cases
      needed repeat aspiration among which 3 resolved in 8 weeks, and one needed
      surgical excision. CONCLUSIONS: We recommend needle aspiration as a simple, safe,
      chief and effective modality, which helps in diagnosis as well as in management
      of suppurative BCG lymphadenitis.

PMID- 25949056
TI  - Depressed Monocytic Activity may be a Predictor for Sepsis.
AB  - INTRODUCTION: Trauma is one of the leading causes of mortality worldwide with
      infections as important causes of death in such patients. Bacterial infections
      cause activation of monocytes with excessive synthesis of pro-inflammatory
      cytokines. Hence, this prospective study was conducted to assess the activity of
      monocytes in traumatized sepsis patients using flow cytometry and to assess if
      they have any prognostic potential. MATERIALS AND METHODS: A total of 16
      consecutive trauma patients with sepsis and having positive blood culture were
      enrolled, along with four healthy controls during the period of March 2013 to
      July 2013. Blood from septic patients were collected on the same day when blood
      culture was positive and on days 2 and 5 thereafter. Surface staining for
      monocytes with CD14 and intracellular staining for interleukin-6 (IL-6) and tumor
      necrosis factor-alpha (TNF-alpha) was done and results were analyzed by flow
      cytometer. Procalcitonin (PCT) assay was done using MiniVidas. Complete clinical
      follow-up was done for the patients. RESULTS: Of the 16 patients, four died due
      to infections by various microorganisms. Isolated abdominal trauma (25%) was the
      most common injury among the enrolled patients of sepsis. Levels of TNF-alpha
      were significantly decreased when stimulated with lipopolysaccharide in the fatal
      patients as compared to the healthy controls. Patients having sepsis who survived
      had an increased level of TNF-alpha during the follow-up periods. CONCLUSION:
      This study showed that activity of monocytes to produce TNF-alpha and IL-6 were
      reduced in severe sepsis. Early identification of such immune-paralysis can help
      in earlier intervention to salvage this vulnerable trauma population.

PMID- 25949057
TI  - Klebsiella Pneumoniae in Septicemic Neonates with Special Reference to Extended
      Spectrum beta-lactamase, AmpC, Metallo beta-lactamase Production and Multiple
      Drug Resistance in Tertiary Care Hospital.
AB  - BACKGROUND: beta-lactamases viz., extended spectrum beta-lactamase (ESBL), AmpC,
      and metallo beta-lactamase (MBL) production in Klebsiella pneumoniae has led to a
      serious concern about septicemic neonates in Neonatal Intensive Care Units due to
      high resistance against commonly used antimicrobials. PURPOSE: To study the
      prevalence of ESBL, AmpC, and MBL production in K. pneumoniae isolates in
      neonatal septicemia, to check antimicrobial susceptibility to various drugs
      including tigecycline; and to assess burden of multiple drug resistance (MDR).
      MATERIALS AND METHODS: Total 24 clinical isolates of K. pneumoniae isolated from
      318 blood samples of suspected cases of neonatal septicemia were studied.
      Isolates were screened for ESBL, AmpC, and MBL production by Clinical and
      Laboratory Standards Institute (CLSI) disk method, AmpC cefoxitin screen, and
      imipenem, meropenem, ceftazidime disk screen respectively; and confirmation was
      done by CLSI phenotypic disk confirmatory test, AmpC sterile disk method, and
      imipenem ethylenediamine tetracetic acid double disk synergy test respectively.
      Antimicrobial susceptibility was determined by Kirby-Bauer's disk diffusion
      method. Efficacy of tigecycline was evaluated using United States Food and Drug
      Administration guidelines. RESULTS: Of the 24 K. pneumoniae isolates, co
      production of AmpC + MBL was found in more number of isolates (67%) (P < 0.0001)
      compared to single enzyme production (ESBL and MBL 8% both, AmpC 12.5%). Rate of
      resistance for penicillins and cephalosporins was highest. Susceptibility was
      more for imipenem, co-trimoxazole, and meropenem. Nonsusceptibility to
      tigecycline was low (21%). A total of 23 (96%) isolates were MDR. CONCLUSIONS:
      Routine detection of ESBL, AmpC, and MBL is required in laboratories. Carbapenems
      should be kept as a last resort drugs. Trend of tigecycline susceptibility has
      been noted in the study. Continued monitoring of susceptibility pattern is
      necessary to detect true burden of resistance for proper management.

PMID- 25949058
TI  - Magnitude of enterococcal bacteremia in trauma patients admitted for intensive
      trauma care: a tertiary care experience from South asian country.
AB  - BACKGROUND: Bloodstream infection (BSI) and bacteremias due to Enterococcus spp.
      are increasing worldwide with the current need to understand its causes among
      hospitalized trauma patients. Hence, the study was conducted. METHODOLOGY: A 3
      year retrospective laboratory cum clinical based study was performed at a level I
      trauma center in India. Patients with health care associated enterococcal
      bacteremia were identified using the hospital database, their episodes of
      BSI/bacteremia calculated and their clinical records and treatment were noted.
      RESULTS: A total of 104 nonrepetitive Enterococcus spp. was isolated of which
      Enterococcus faecium was the most common (52%). High-level resistance to
      gentamicin high-level aminoglycoside resistance was seen in all the Enterococcus
      spp. causing bacteremia, whereas a low resistance to vancomycin and teichoplanin
      was observed. Overall mortality was more in patients infected with vancomycin
      resistant Enterococcus (5/11, 46%) compared to those with vancomycin sensitive
      Enterococcus (9/93, 10%); though no significant association of mortality with
      Enterococcus spp. bacteremia (P > 0.05) was seen. The rate of bacteremia due to
      Enterococcus spp. was 25.4 episodes/1,000 admissions (104/4,094) during the study
      period. CONCLUSION: Enterococcal bacteremia is much prevalent in trauma care
      facilities. Here, a microbiologist can act as a sentinel and help in preventing
      such infections.

PMID- 25949059
TI  - Comparison of Bone Mineral Density, T-Scores and Serum Zinc between Diabetic and
      Non Diabetic Postmenopausal Women with Osteoporosis.
AB  - CONTEXT: Postmenopausal osteoporosis is a public health problem. Diabetics are at
      increased risk of osteoporosis-related fractures. Zinc (Zn) has a role in
      collagen metabolism, and its levels are altered in diabetes. AIMS: The aim was to
      compare bone mineral density (BMD), T-score and serum Zn between diabetic and
      nondiabetic postmenopausal women with osteoporosis to see if they influence
      increased fracture risk in diabetes. SETTINGS AND DESIGN: It is a cross.sectional
      study conducted at Department of Biochemistry, Jawaharlal Nehru Medical College,
      Belgaum. MATERIALS AND METHODS: Thirty type 2 diabetic and 30 age-matched (aged
      45-75 years) nondiabetic Dual energy X-ray absorptiometry (DEXA) confirmed
      postmenopausal osteoporotics were included from January 2011 to March 2012. Serum
      Zn was analyzed by atomic absorption spectrophotometry. STATISTICAL ANALYSIS
      USED: Mean and standard deviation of the parameters of the two groups were
      computed and compared by unpaired Student's t-test. Relationship between
      variables was measured by Karl Pearson's correlation co-efficient. A statistical
      significance is set at 5% level of significance (P < 0.05). RESULTS: T-score was
      significantly higher in diabetics compared with nondiabetics (-2.84 +/- 0.42 vs. 
      3.22 +/- 0.74) P < 0.05. BMD and serum Zn of diabetics showed a significant
      positive correlation with body mass index (BMI). CONCLUSIONS: Type 2 diabetic
      postmenopausal osteoporotics have a higher T-score than the nondiabetics. High
      BMI in type-2 diabetes mellitus (T2DM) may contribute to high BMD and may be a
      protective factor against zincuria. Increased fracture risk in T2DM could be due
      to other factors like poor bone quality due to hyperglycemia rather than BMD.
      Strict glycemic control is of paramount importance.

PMID- 25949060
TI  - Microbial flora in chronic periodontitis: study at a tertiary health care center
      from north karnataka.
AB  - BACKGROUND AND OBJECTIVE: Periodontitis is a major public health problem in India
      with a prevalence of 60-80%. If untreated it acts as a risk factor for systemic
      diseases. Data on anaerobic periodontal microflora in the Indian population is
      very scarce. Hence, this study was undertaken to know the nature of oral
      microbiota in chronic periodontitis in this region of India and also the
      semiquantitative study in pre- and post-treatment group and to determine
      antibiotic susceptibility pattern for aerobic isolates. MATERIALS AND METHODS:
      The present study was conducted on 60 cases. Material was collected from the
      subgingival pockets in patients with chronic periodontitis attending the
      Periodontology, Outpatient Department. Clinical samples were transported to the
      laboratory in fluid thioglycollate medium. Initially Gram's stain and Fontana
      stains were done. Aerobic, anaerobic, and microaerophilic culture were put up.
      Antibiotic sensitivity test was done for aerobic isolates. RESULTS: Sixty samples
      yielded 121 isolates of which 78.34% were polymicrobial, 11.66% were
      monomicrobial and oral commensals were grown in 10% cases. Out of 121 isolates
      91.74% were anaerobic, 7.43% were aerobic and 0.83% were microaerophilic.
      Fusobacterium species was the most common isolate among anaerobes. Using "paired
      t-test" "P" value was significant indicating significant reduction in colony
      count after phase-I periodontal therapy. CONCLUSION: This study has shown that
      anaerobic bacteria are important cause of chronic periodontitis, along with
      aerobes and microaerophilic organisms. Fusobacterium spp, Bacteroides fragilis,
      Porphyromonas spp and Prevotella intermedia are the most common anaerobic
      pathogens. Bacterial culture methods are still economical and gold standard.

PMID- 25949061
TI  - A rare case of mycetoma due to curvularia.
AB  - Mycetoma due to Curvularia is a rare clinical entity. Here, we report a case of
      27-year-old female presented with multiple swellings and discharging wounds
      around left shoulder joint since 12 years. Local examination showed diffuse
      nodular swellings over left anterior chest wall, posterior chest wall, and
      axilla. Multiple nodules and discharging sinuses were seen. Fungal culture of the
      biopsy of the lesion revealed Curvularia species. Patient showed significant
      clinical improvement with itraconazole therapy. 

PMID- 25949062
TI  - Melioidosis as a cause of acute abdomen in immuno-competent male from eastern
      India.
AB  - Though melioidosis is rare in India, it has gained importance as one of the most
      potent emerging infections. In India, the cases have been under-reported because
      of the lack of awareness. The majority of cases present with multifocal pyogenic
      infections with septicemia. We present an unusual case of melioidosis presenting
      as acute intestinal perforation. The organism was ceftazidime resistant, and we
      successfully treated the case with imipenem and doxycyclin. This case highlights
      ruling out the possibility of melioidosis in acute abdomen and existence of
      ceftazidime resistant cases in India. 

PMID- 25949063
TI  - Calcified amyloid tumor of neck with exuberant giant cell reaction.
AB  - Amyloidosis is a group of disorders characterized by an extracellular deposition
      of an abnormal amount of proteins in a variety of organs resulting from abnormal
      folding of protein. It typically presents as disseminated deposits. Tumor like
      localized presentation of amyloidosis in the absence of systemic amyloidosis is
      referred to as amyloidoma or amyloid tumor. Amyloidoma is the least common
      presentation of tissue amyloid deposition. Amyloidoma of soft tissue is again a
      very rare entity, especially in the neck region. Calcification and minimum giant
      cell reaction can occur in amyloidoma. However, extensive calcification and
      exuberant giant cell reaction in amyloidoma of soft tissue neck make it difficult
      to diagnose. In this report, we discuss such a rare case with its differential
      diagnoses. 

PMID- 25949064
TI  - Hepatic tuberculosis mimicking metastasis in a case of carcinoma sigmoid colon.
AB  - Tuberculosis (TB) presenting as isolated liver mass without clinical evidence of
      TB is difficult to diagnose preoperatively and is usually mimicked by primary or
      metastatic carcinoma of the liver. Hepatic TB associated with carcinoma colon is
      a rare association which has very rarely been reported in the literature. This
      case illustrates the diagnostic difficulties of hepatic TB and the need to
      consider it in the differential diagnosis of hepatic nodular lesions in carcinoma
      colon patients. Here, we report a case of 48-year-old female who presented in the
      casualty with features of acute intestinal obstruction. Preoperatively a mass was
      seen at the hepatic flexure along with three lesions in the liver presumed to be
      metastatic in origin. However, histopathology of the mass revealed adenocarcinoma
      colon and the liver lesion proved to be hepatic TB. We wish to highlight that on
      encountering a hepatic lesion in a carcinoma colon patient the possibility of
      hepatic TB should also be kept in mind apart from the obvious possibility of
      metastasis especially in an endemic country like India. 

PMID- 25949065
TI  - Primary B-cell Non-Hodgkin Lymphoma of Gallbladder Presenting as Cholecystitis.

PMID- 25949066
TI  - Staphylococcal small colony variants from a libyan hospital.

PMID- 25949067
TI  - Exaggeration of hypoxic lung injury in a patient with glucose-6-phosphate
      dehydrogenase deficiency.

PMID- 25949068
TI  - Diabetic retinopathy: a global epidemic.

PMID- 25949070
TI  - Imaging in diabetic retinopathy.
AB  - While the primary method for evaluating diabetic retinopathy involves direct and
      indirect ophthalmoscopy, various imaging modalities are of significant utility in
      the screening, evaluation, diagnosis, and treatment of different presentations
      and manifestations of this disease. This manuscript is a review of the important
      imaging modalities that are used in diabetic retinopathy, including color fundus
      photography, fluorescein angiography, B-scan ultrasonography, and optical
      coherence tomography. The article will provide an overview of these different
      imaging techniques and how they can be most effectively used in current practice.

PMID- 25949069
TI  - Molecular mechanisms of diabetic retinopathy: potential therapeutic targets.
AB  - Diabetic retinopathy (DR) is the leading cause of blindness in working-age adults
      in United States. Research indicates an association between oxidative stress and
      the development of diabetes complications. However, clinical trials with general
      antioxidants have failed to prove effective in diabetic patients. Mounting
      evidence from experimental studies that continue to elucidate the damaging
      effects of oxidative stress and inflammation in both vascular and neural retina
      suggest its critical role in the pathogenesis of DR. This review will outline the
      current management of DR as well as present potential experimental therapeutic
      interventions, focusing on molecules that link oxidative stress to inflammation
      to provide potential therapeutic targets for treatment or prevention of DR.
      Understanding the biochemical changes and the molecular events under diabetic
      conditions could provide new effective therapeutic tools to combat the disease. 

PMID- 25949071
TI  - Diabetic retinopathy and systemic factors.
AB  - Diabetic retinopathy, an oculardisease, is governed by systemic as well as local
      ocular factors. These include primarily chronic levels of blood glucose.
      Individuals with chronically elevated blood glucose levels have substantially
      more, and more severe, retinopathy than those with lower blood glucose levels.
      The relationship of blood glucose to retinopathy is continuous, with no threshold
      although individuals with hemoglobin A1c levels (a measure of chronic glycemia)
      <6.5%, generally develop little or no retinopathy. Blood pressure levels have
      been claimed to influence retinopathy development and progression, but multiple
      controlled clinical trials of antihypertensive agents in diabetic subjects have
      produced only weak evidence of benefit from blood pressure lowering on the
      incidence and progression of diabetic retinopathy. Elevated blood lipids seem to
      play a role in the progression of retinopathy, and two trials of fenofibrate, a
      lipid-lowering agent that has not proved effective in preventing cardiovascular
      disease, have shown benefit in preventing retinopathy progression. The mechanism
      of this effect may not, however, be directly related to the reduction in blood
      lipids. Finally, there is strong, but only circumstantial, evidence for a genetic
      or epigenetic influence on the pathogenesis of diabetic retinopathy. Despite the
      power of large-scale epidemiologic studies and modern molecular biological and
      computational techniques, the gene or genes, which predispose or protect against
      the development and progression of diabetic retinopathy remain elusive. 

PMID- 25949072
TI  - Recent developments in laser treatment of diabetic retinopathy.
AB  - Laser photocoagulation has been the mainstay of diabetic retinopathy treatment
      since its development in mid-20(th) century. With the advent of antivascular
      endothelial growth factor therapy, the role of laser therapy appeared to be
      diminished, however many advances in laser technology have been developed since.
      This review will describe recent advances in laser treatment of diabetic
      retinopathy including pattern scan laser, short-pulse duration and a reduced
      fluence laser, and navigated laser system for proliferative diabetic retinopathy
      and macular edema. 

PMID- 25949074
TI  - Telemedicine in diabetic retinopathy: current status and future directions.
AB  - Telemedicine is exchange of medical data by electronic telecommunications
      technology that allows a patient's medical problems evaluated and monitored by a
      remotely located physician. Over the years, telemedicine and telescreening have
      become important components in health care, in both disease detection and
      treatment. Highly visual and image intensive ophthalmology is uniquely suited for
      telemedicine. Because of rising disease burden coupled with high opportunity cost
      in detection, diabetic retinopathy is an ideal ophthalmic disease for
      telescreening and decision-making. It fits to Wilson and Jungner's all 10
      criteria of screening for chronic diseases and the American Telehealth
      Association's 4 screening categories. 

PMID- 25949073
TI  - Novel pharmacotherapies in diabetic retinopathy.
AB  - This is a summary of current and emerging pharmacologic therapies utilized in the
      treatment of diabetic retinopathy (DR). Current therapies, such as ranibizumab,
      bevacizumab, triamcinolone acetonide, and fluocinolone acetonide, inhibit
      angiogenesis and inflammation and may be used alone or in combination with laser
      treatment. Emerging therapies aim to reduce oxidative stress or inhibit other
      signal transduction pathways, including the protein kinase C cascade and aldose
      reductase pathway. Future therapies may target other molecules crucial to the
      pathogenesis of DR, including hepatocyte growth factors and matrix
      metalloproteinase 9. Finally, the emergence of novel mechanisms of medication
      delivery may also be on the horizon. 

PMID- 25949075
TI  - Prevalence and histopathological characteristics of corneal stromal dystrophies
      in Saudi Arabia.
AB  - PURPOSE: The aim was to determine the frequency and describe the main
      histopathologic features of corneal stromal dystrophy in Saudi Arabia. METHODS: A
      single-center, retrospective analysis of 193 corneal specimens diagnosed with
      stromal dystrophy. All samples were retrieved from the Histopathology Department
      at King Khaled Eye Specialist Hospital over a 10-year period (2002 to December
      31, 2011). Cases of stromal dystrophy undergoing keratoplasty were included in
      the study. Routine histopathologic stains and specific stains were used to
      determine a diagnosis. The corresponding demographic data and basic
      clinical/surgical information were collected via chart review. RESULTS: The study
      sample was comprised of 193 eyes. The final diagnoses were macular corneal
      dystrophy (MCD) in 180 (93.26%) eyes, granular corneal dystrophy (GCD) in 9
      (4.66%) and lattice corneal dystrophy (LCD) in 4 (2.07%) eyes. The mean age at
      presentation was 27.03 years for MCD, 26.33 years for GCD and 53.75 years for
      LCD. The interval between diagnosis and surgical intervention was not
      statistically different between the macular and granular groups (P = 0.141).
      There was a positive family history for the MCD (37.22%) and GCD (44.44%) groups.
      All eyes underwent penetrating keratoplasty (PKP) except 10 MCD cases that
      underwent lamellar keratoplasty. Diffuse stromal deposits were present in 87.2%
      of MCD corneas and 66.67% of GCD corneas. Seventeen eyes with MCD were
      misdiagnosed as GCD. None of the LCD cases were clinically identified since all
      of these cases were diagnosed as corneal scarring. In eyes with MCD that
      underwent PKP, there was diffuse stromal involvement (in 87.22% eyes) and changes
      in Descemet's membrane (in 53.5% eyes). CONCLUSION: This pathological study
      suggested that MCD was the most common corneal stromal dystrophy that required
      keratoplasty in Saudi Arabia. Patient with MCD and GCD presented at a
      significantly younger age than LCD. The clinical diagnosis of MCD is not achieved
      in all cases likely due to a more severe phenotype in the Saudi population or the
      presence of corneal scarring that is associated with previous trachoma, which
      obscures the classical appearance of LCD. We believe that PKP is first-line
      surgical treatment, especially for MCD because it involves all corneal layers.
      However, deep stromal involvement and changes in Descemet's membrane in MCD
      should be considered when selecting the surgical procedure.

PMID- 25949076
TI  - Quantitative Analysis of Segmented Fluorescein Angiography Images for the Follow
      up of Choroidal Neovascular Membrane.
AB  - PURPOSE: The aim of this study was to evaluate choroidal neovascular (CNV)
      lesions with fluorescein angiography (FA) and to identify quantitative parameters
      and correlate these parameters to treatment outcomes. SUBJECTS AND METHODS: This
      institution based cross-sectional study evaluated 30 eyes with active sub-foveal
      predominantly classic CNV treated with bevacizumab. Pre- and post-injection
      segmented FA images were analyzed. Lesion area and CNV lesion were manually
      delineated. Outcome measure was the change 1-month after each injection in
      different intensity values (0-255 divided in eight regions A [lowest intensity]
      to H [highest intensity] on a linear scale) in lesion area, perimeter, greatest
      linear dimension (GLD), area, visual acuity (VA) and central macular thickness
      (CMT). RESULTS: At month 3, statistically significant changes from baseline
      occurred in VA, CMT, lesion area, GLD and perimeter (P < 0.05 all comparisons).
      Change in CMT from baseline to 3 months postinjection was correlated with change
      in VA (P = 0.009, r = 0.469) and intensity regions B (P = 0.001, r = -0.565), D
      (P = 0.001, r = 0.560), E (P = 0.035, r = 0.386). At month 3, change in intensity
      values 0-63 (A + B) was negatively correlated with CMT (P = 0.001, r = -0.575)
      and lesion area (P = 0.019, r = -0.427); change in intensity values 64-223 (C-G)
      was positively correlated with CMT (P = 0.000, r = 0.636) and lesion area (P =
      0.002, r = 0.551). CONCLUSIONS: Decrease in area, GLD, perimeter and area with
      intensity >= 64 on segmented FA were associated with a favorable outcome of
      treatment. These parameters may be useful adjuncts to existing evaluation
      techniques during follow-up of CNV.

PMID- 25949077
TI  - Enhanced depth imaging optical coherence tomography of circumscribed choroidal
      hemangioma in 10 consecutive cases.
AB  - PURPOSE: The purpose was to evaluate the features of circumscribed choroidal
      hemangioma using spectral-domain enhanced depth imaging optical coherence
      tomography (EDI-OCT). DESIGN: Retrospective observational case series.
      PARTICIPANTS: Ten patients with newly diagnosed circumscribed choroidal
      hemangioma. METHODS: Spectral-domain EDI-OCT was performed with a Heidelberg
      Spectralis HRA + OCT (Heidelberg Engineering, Heidelberg, Germany). MAIN OUTCOME
      MEASURES: Tumor thickness and EDI-OCT features. RESULTS: The mean tumor diameter
      for all eyes was 5.4 mm and mean tumor thickness was 1187 MUm by EDI-OCT compared
      to 2400 MUm by ultrasonography. EDI-OCT imaged all tumors as smooth with a gently
      sloping anterior contour, gradual choroidal expansion, expansion of medium and
      large size choroidal vessels without compression of choriocapillaris, and intact
      Bruch's membrane (n = 10, 100%). The height of the medium and large choroidal
      vessels within the tumor compared to normal medium and large vessels was
      comparatively increased by a mean of 265% (medium vessels) and 576% (large
      vessels). Outer retinal abnormalities included subretinal fluid (n = 7, 70%),
      lipofuscin deposition (n = 1, 10%), irregularity and thinning of retinal pigment
      epithelium and absence or irregularity of the ellipsoid layer (n = 4, 40%),
      absent external limiting membrane (n = 2, 20%), and disruption of the outer
      nuclear layer and outer plexiform layer (n = 3, 30%). The inner retinal
      abnormalities included irregularity of inner nuclear layer and structural loss or
      edema of inner plexiform layer (n = 3, 30%). The ganglion cell layer and nerve
      fiber layer were intact (n = 10, 100%). CONCLUSION: EDI-OCT of circumscribed
      choroidal hemangiomas depicts a smooth, gently sloping choroidal mass with
      expansion of medium and large size choroidal vessels without compression of the
      choriocapillaris. Structural abnormalities of outer and inner retinal layers were
      noted.

PMID- 25949078
TI  - Incidence and Determinants of Endophthalmitis within 6 Months of Surgeries over a
      2-Year Period at King Khaled Eye Specialist Hospital, Saudi Arabia: A Review.
AB  - BACKGROUND: We present the incidence and determinants of endophthalmitis between
      July 2010 and June 2012 at King Khaled Eye Specialist Hospital, Riyadh, Saudi
      Arabia. On its basis, we recommended recommendations to strengthen the infection
      prevention and control strategies. METHODS: This is a retrospective review of
      health records type of study. The details of cases reported having
      endophthalmitis among those operated in 2 years of study period were studied. The
      incidence of endophthalmitis was calculated for different eye surgeries and
      epidemiological variables. The causative organisms in vitreous tap were reviewed.
      The visual outcomes 6 weeks following intervention/treatment of endophthalmmitis
      were also studied. RESULTS: Of the 22,554 cases operated, 17 developed
      endophthalmitis. The incidence was 0.08% (95% confidence interval [CI] 0.04
      0.11). The incidence of endophthlamitis among cataract surgeries was 0.12% (95%
      CI 0.04-0.21). Five specimens did not show any bacteria or fungus. Staphylococcus
      epidermis (3 cases) was the main pathogen identified. In 8 (47%) eyes, vision
      deteriorated in spite of treatment. In 5 (29%) eyes, it became stable and in 4
      (23.5%) eyes, it improved following treatment. Signs of infection were noted in
      1(st) week, 3 weeks and 12 weeks in 4, 6 and 5 eyes respectively. Late
      presentation of infection (6 months postoperatively) was reported in two eyes.
      CONCLUSIONS: A vigilant infection control unit in a large eye hospital helps in
      monitoring endophthalmitis related catastrophes and suggests timely preventive
      measures to reduce the occurrence and appropriate measures to limit visual
      disabilities following eye surgery related endophthalmitis.

PMID- 25949079
TI  - Risk factors and clinical outcomes of bacterial and fungal scleritis at a
      tertiary eye care hospital.
AB  - PURPOSE: The aim was to analyze demographics, risk factors, pathogenic organisms,
      and clinical outcome in cases with microbiologically proven bacterial or fungal
      scleritis. MATERIALS AND METHODS: Retrospective review of all the medical records
      of patients with microbiologically proven infectious scleritis examined from
      March 2005 to December 2009 in the cornea services of L. V. Prasad Eye Institute,
      Hyderabad, India was done. RESULTS: Forty-two eyes of 42 patients were included
      in this study. The mean age at presentation was 48.52 +/- 14.10 years (range: 12
      70). Surgery was the major risk factor seen in 24 eyes (58.5%). Scleral infection
      was noted after vitreoretinal surgery (with scleral buckle) in 15 eyes, cataract
      surgery in 3 eyes, pterygium surgery in 3 eyes, corneoscleral tear repair and
      scleral buckle surgery in 3 eyes. Sixteen eyes (39%) were on systemic or topical
      steroids at the time of presentation. History of injury was noted in 9 eyes (22%)
      and diabetes mellitus in 7 patients (17%). Associated keratitis was noted in 9
      eyes (21.4%). The scleral abscess was unifocal in 33 eyes (78.5%), multifocal in
      6 eyes (14.2%) and diffuse in 3 eyes (7.14%). The final follow-up ranged from 24
      days to 37 months. The final visual acuity was better in 18 eyes (42.8%), stable
      in 13 (30.9%), and deteriorated in 7 eyes (16.6%). Recurrence was seen in 4 eyes
      (9.5%). CONCLUSIONS: Surgery is a major risk factor for infectious scleritis in
      our series. Fungus was the most common organism isolated. Thorough debridement
      and intensive use of medications have improved the outcome.

PMID- 25949080
TI  - Changes in corneal topography and biomechanical properties after collagen cross
      linking for keratoconus: 1-year results.
AB  - PURPOSE: To evaluate changes in corneal topography and biomechanical properties
      after collagen cross-linking (CXL) for progressive keratoconus. PATIENTS AND
      METHODS: Collagen cross-linking was performed on 97 eyes. We assessed uncorrected
      visual acuity (UCVA) and best corrected visual acuity (BCVA). Corneal topography
      indices were evaluated using placido disc topography, scanning slit anterior
      topography (Orbscan II), and rotating Scheimpflug topography (Pentacam). Specular
      microscopy and corneal biomechanics were evaluated. RESULTS: A 1-year-follow-up
      results revealed that UCVA improved from 0.31 to 0.45 and BCVA changed from 0.78
      to 0.84 (P < 0.001). The mean of average keratometry value decreased from 49.62
      to 47.95 D (P < 0.001). Astigmatism decreased from 4.84 to 4.24 D (P < 0.001).
      Apex corneal thickness decreased from 458.11 to 444.46 MUm. Corneal volume
      decreased from 56.66 to 55.97 mm(3) (P < 0.001). Posterior best fit sphere
      increased from 55.50 to 46.03 mm (P = 0.025). Posterior elevation increased from
      99.2 to 112.22 MUm (P < 0.001). Average progressive index increased from 2.26 to
      2.56 (P < 0.001). A nonsignificant decrease was observed in mean endothelial
      count from 2996 to 2928 cell/mm(2) (P = 0.190). Endothelial coefficient of
      variation (CV) increased nonsignificantly from 18.26 to 20.29 (P = 0.112).
      Corneal hysteresis changed from 8.18 to 8.36 (P = 0.552) and corneal resistance
      factor increased from 6.98 to 7.21 (P = 0.202), so these changes were not
      significant. CONCLUSION: Visual acuity and K values improved after CXL. In spite
      of the nonsignificant increase in endothelial cell count and increase in the CV,
      CLX seems to be a safe treatment for keratoconus. Further studies with larger
      sample sizes and longer follow-up periods are recommended.

PMID- 25949081
TI  - Are we monitoring the quality of cataract surgery services? A qualitative
      situation analysis of attitudes and practices in a large city in South Africa.
AB  - PURPOSE: To evaluate the current quality "assurance" and "improvement"
      mechanisms, the knowledge, attitudes and practices of cataract surgeons in a
      large South African city. METHODOLOGY: A total of 17 in-depth semi-structured
      interviews were conducted with ophthalmologists in June 2012 at 2 tertiary
      institutions in the Republic of South Africa. Recruitment of the purposive sample
      was supplemented by snowball sampling. The study participants were 5 general
      ophthalmologists and 2 pediatric ophthalmologists; 4 senior and 4 junior
      registrars and a medical officer. Participants were interviewed by a trained
      qualitative interviewer. The interview lasted between 20 and 60 min. The
      interviews were recorded, transcribed verbatim and analyzed for thematic content.
      RESULTS: Mechanisms for quality assurance were trainee logbooks and subjective
      senior staff observation. Clinicians were encouraged, but not obliged to self
      audit. Quality improvement is incentivized by personal integrity and ambition.
      Poorly performing departments are inconspicuous, especially nationally, and
      ophthalmologists rely on the impression to gauge the quality of service provided
      by colleagues. Currently, word of mouth is the method for determining the better
      cataract surgical centers. CONCLUSION: The quality assurance mechanisms were
      dependent on insight and integrity of the individual surgeons. No structures were
      described that would ensure the detection of surgeons with higher than expected
      complication rates. Currently, audits are not enforced, and surgical outcomes are
      not well monitored due to concerns that this may lead to lack of openness among
      ophthalmologists.

PMID- 25949082
TI  - Four petals evisceration for atrophia bulbi.
AB  - PURPOSE: To study the use of four petals evisceration in atrophia bulbi to allow
      insertion of large orbital implant. MATERIALS AND METHODS: An interventional case
      series. All cases were atrophia bulbi. The axial lengths (AL) of atrophic and
      contralateral normal eye were measured. It was planned to use implant 3 mm
      smaller than AL of the contralateral normal eye. Four petals evisceration was
      used in all cases. RESULTS: Twenty cases were included. The mean age was 27.08 +/
      16.07 years. The mean axial length (AL) of atrophic eyes was 16.97 +/- 1.42 mm.
      In 75% of cases, the planned implant was inserted. In all cases, the implant
      diameter was larger than AL of atrophic eye by a mean of 2.57 +/- 0.64 mm. The AL
      of atrophic eye did not affect the implant size. The mean follow-up period was
      22.4 +/- 10.1 months. Implant exposure was not recorded in any case. Volume
      deficiency was recorded in 2 cases (10%). CONCLUSIONS: Four petals evisceration
      facilitated the use of suitable sized implant in atrophia bulbi with minimal
      complications.

PMID- 25949083
TI  - Eyelid Tumors at the University Eye Clinic of Ioannina, Greece: A 30-year
      Retrospective Study.
AB  - AIMS: The aim was to describe the epidemiology of primary eyelid tumors over a 30
      year period at the Ioannina University Eye Clinic, Greece. MATERIALS AND METHODS:
      This retrospective case series examined the histopathology of eyelid tumor
      specimens of patients treated between 1983 and 2012. Data were collected on
      patient age, gender, location of the lesion, extent of tumor excision and
      recurrence. Descriptive and inferential statistics were used to describe the
      study subgroups. RESULTS: A total of 851 eyelid tumors comprised the study
      sample. There were 351 (41.2%) malignant cases and 500 (58.8%) benign cases. For
      malignant tumors, there were 86% basal cell carcinomas, 7% squamous cell
      carcinomas, and 7% basosquamous cell carcinomas. The benign eyelid lesions were
      comprised of 20% cysts, 18% seborrheic keratosis, 13% nevi, and 13% papillomas.
      Benign eyelid lesions occurred with equal frequency in the upper and lower lids.
      Malignant lesions were more frequently located in the lower lid. The mean age at
      diagnosis was 49 +/- 1.45 years for patients with benign lesions and 67 +/- 1.6
      years for patients with malignant lesions. CONCLUSIONS: In this Greek cohort,
      benign eyelid lesions affected mostly young individuals, and malignant lesions
      occurred predominantly in elderly patients. Males and females were equally
      affected by malignant lesions, and recurrence after surgical excision was rare.

PMID- 25949084
TI  - Comparison of the Corneal Power Measurements with the TMS4-Topographer, Pentacam
      HR, IOL Master, and Javal Keratometer.
AB  - PURPOSE: The aim was to compare the corneal curvature and power measured with a
      corneal topographer, Scheimpflug camera, optical biometer, and Javal keratometer.
      MATERIALS AND METHODS: A total of 76 myopic individuals who were candidates for
      photorefractive keratectomy were selected in a cross-sectional study. Manual
      keratometry (Javal Schiotz type; Haag-Streit AG, Koeniz, Switzerland), automated
      keratometry (IOL Master version 3.02, Carl Zeiss Meditec, Jena, Germany),
      topography (TMS4, Tomey, Erlangen, Germany), and Pentacam HR (Oculus, Wetzlar,
      Germany) were performed for all participants. The 95% limits of agreement (LOAs)
      were reported to evaluate the agreement between devices. RESULTS: The mean
      corneal power measurements were 44.3 +/- 1.59, 44.25 +/- 1.59, 43.68 +/- 1.44,
      and 44.31 +/- 1.61 D with a Javal keratometer, TMS4-topographer, the Pentacam and
      IOL Master respectively. Only the IOL Master showed no significant difference
      with Javal keratometer in measuring the corneal power (P = 0.965). The
      correlations of the Javal keratometer with TMS4-topography, Pentacam, and IOL
      Master was 0.991. 0.982, and 0.993 respectively. The 95% LOAs of the Javal
      keratometer with TMS4-topography, Pentacam, and IOL Master were - 0.361 to 0.49, 
      0.01 to 1.14, and - 0.36 to 0.36 D, respectively. CONCLUSION: Although the
      correlation of Pentacam, TMS4-topography, IOL Master, and Javal keratometer in
      measuring keratometry was high, only the IOL Master showed no significant
      difference with the Javal keratometer. The IOL Master had the best agreement with
      Javal keratometry.

PMID- 25949085
TI  - Bacterial keratitis in a tertiary eye centre in Iran: a retrospective study.
AB  - PURPOSE: To report the characteristics and laboratory findings of 182 patients
      with bacterial keratitis diagnosed at Farabi Eye Hospital in Tehran, Iran.
      MATERIALS AND METHODS: In this retrospective study, data were collected on
      demographics, risk factors, location, size and depth of the ulcer, height of the
      hypopyon, uncorrected visual acuity, results of smear and culture tests, and
      antibiotic sensitivity of cultured bacteria. RESULTS: There were 110 (60.4%)
      males and 72 (39.6%) females with an average age of 56.0 +/- 2.3 years. Ocular
      trauma (17.6%) and positive history of corneal surgery (14.3%) were major risk
      factors. The mean age of contact lens users was 22.5 +/- 7.7 years. Sixty
      patients (33%) used topical antibiotics, 21 (11.5%) patients utilized topical
      steroid, and 26 (14.3%) cases used both topical antibiotic and steroid at
      presentation. Culture results were, 81 (44.5%) cases were Gram-positive, 63
      (34.6%) were Gram-negative, 10 (5.5%) were mixed bacteria and in 28 (15.4%) cases
      had detected growth. The isolated bacterial species from the corneal ulcers were
      less resistant to ceftazidime (6%) and amikacin (6%). The majority of patients
      were treated with medical therapy; however, 81 cases (44.5%) received at least
      one surgical procedure. CONCLUSION: Among the patients with bacterial corneal
      ulcers, trauma was the most common risk factor. Over-the-counter antibiotic and
      steroid were commonly used in the majority of patients. The most common bacteria
      isolated were Gram-positives, and they were less resistant to ceftazidime and
      amikacin. Penetrating keratoplasty was the most common surgical procedure in
      patient who required surgery.

PMID- 25949086
TI  - Idiopathic Peripapillary Subretinal Neovascular Membrane in a Young Woman with
      Recurrence of the Lesion during Pregnancy after Treatment with Intravitreal
      Bevacizumab.
AB  - We report a 27-year-old woman who was diagnosed with idiopathic peripapillary
      subretinal neovascular membrane (PSRNVM) in her left eye with best-corrected
      visual acuity (BCVA) of 20/160. She had been treated by three monthly doses of
      intravitreal bevacizumab (1.25 mg/0.05 ml) at 4-week intervals, which showed a
      favorable response. The treatment led to regression of the choroidal neovascular
      membrane (CNVM) with complete resorption of subretinal fluid and improvement of
      BCVA to 20/25. Subsequently, recurrence of the CNVM was observed during pregnancy
      (28 months after treatment). To the best of our knowledge, this is the first
      report of recurrence of idiopathic PSRNVM during pregnancy. 

PMID- 25949087
TI  - Enhanced depth imaging optical coherence tomography of precursor cell leukemic
      choroidopathy before and after chemotherapy.
AB  - Serous retinal detachment (SRD) can be the initial manifestation of leukemia.
      Herein, we explore the retinal and choroidal features on enhanced depth imaging
      optical coherence tomography (EDI-OCT) of SRD in a patient with undiagnosed
      leukemia. A 23-year-old male developed blurred visual acuity of 20/200 in the
      right eye oculus dexter (OD) and 20/200 in the left eye oculus sinister (OS).
      Funduscopically, he manifested serous macular detachment in both eyes oculi
      uterque (OU) without hemorrhagic retinal abnormalities. EDI-OCT disclosed macular
      detachment OU and homogeneous, marked choroidal opacification with thickening to
      724 MUm OD and estimated >600 MUm OS and with loss of choroidal detail OU.
      Peripheral blood smears revealed severe thrombocytopenia and normal leukocyte
      count. Peripheral cytochemisty, immunophenotyping, and bone marrow aspirate
      confirmed the presence of atypical lymphoblasts, fulfilling criteria for
      precursor cell leukemia. Following systemic chemotherapy, the visual acuity
      improved to 20/25 OD and 20/20 OS. On EDI-OCT, the choroidal thickening resolved
      to 431 um OD and 443 um OS, leaving a normal choroidal appearance. Massive
      choroidal infiltration with leukemic cells could be the cause of serous macular
      detachment found in patients with newly diagnosed leukemia. 

PMID- 25949088
TI  - Postcataract surgery endophthalmitis caused by acinetobacter lwoffii.
AB  - Acinetobacter lwoffii is a rare cause of endophthalmitis. We report a case of
      acute postoperative endophthalmitis in a female, who was treated successfully
      with pars plana vitrectomy and intravitreal antibiotics. 

PMID- 25949089
TI  - Patch Graft for Corneal Perforation Following Trivial Trauma in Bilateral
      Terrien's Marginal Degeneration.
AB  - A young female presented with blurred vision in the left eye after she rubbed her
      eye. On examination of both eyes, she had 360 degrees  thinning adjacent to the
      limbus, lipid deposition and superficial vascularization with a perforation in
      the left eye. The patient was diagnosed with bilateral Terrien's marginal
      degeneration (TMD) with perforation. Corneal topography of the right eye revealed
      high oblique astigmatism confirming the diagnosis. A peripheral patch graft was
      performed for the left eye. At 18 months postoperatively, the best-corrected
      visual acuity was 20/20 in both eyes. The graft was clear. Topography of right
      eye was stable, and the left eye had oblique astigmatism. Bilateral advanced TMD
      in a young patient presenting with corneal perforation following trivial trauma
      is extremely uncommon. Patch graft may be an option for restoring the globe
      integrity in such cases. Regular follow-up is necessary as the condition
      progresses slowly. 

PMID- 25949091
TI  - Maternal and neonatal risk factors associated with vertical transmission of
      ophthalmia neonatorum in neonates receiving health care in Blantyre, Malawi.

PMID- 25949090
TI  - Amiodarone-induced multiorgan toxicity with ocular findings on confocal
      microscopy.
AB  - Amiodarone is an antiarrhythmic medication that can adversely effect various
      organs including lungs, thyroid gland, liver, eyes, skin, and nerves. The risk of
      adverse effects increases with high doses and prolonged use. We report a 54-year
      old female who presented with multiorgan toxicity after 8 months of low dose (200
      mg/day) amiodarone treatment. The findings of confocal microscopy due to
      amiodarone-induced keratopathy are described. Amiodarone may cause multiorgan
      toxicity even at lower doses and for shorter treatment periods. 

PMID- 25949092
TI  - Response to maternal and neonatal risk factors associated with vertical
      transmission of ophthalmia neonatorum in neonates receiving health care in
      Blantyre, Malawi.

PMID- 25949093
TI  - Social Workers as Research Psychotherapists in an Investigation of Cognitive
      Behavioral Therapy among Rural Older Adults.
AB  - A large proportion of service providers in our country are social workers. The
      use of social workers as mental health therapists however, has not been
      adequately evaluated in the literature. This aim of this study was to evaluate a
      sample of clinically trained, masters-level social workers in their delivery of
      in-home Cognitive Behavioral Therapy (CBT) to a group of primarily rural,
      medically frail older adults. The social workers in this study received extensive
      didactic and experiential CBT training. Audio-taped sessions were randomly
      selected and evaluated independently. Results showed that the social workers
      adequately delivered CBT as measured by the Cognitive Therapy Scale (CTS). Older
      adult participants also evidenced pre-post treatment improvements suggesting that
      the social workers' delivery of CBT facilitated improvement. These results
      suggest that social workers can be viable providers of CBT in clinical and
      research settings.

PMID- 25949094
TI  - Four Strategies for Managing Opioid-Induced Side Effects in Older Adults.

PMID- 25949096
TI  - Identifying driver genes in cancer by triangulating gene expression, gene
      location, and survival data.
AB  - Driver genes are directly responsible for oncogenesis and identifying them is
      essential in order to fully understand the mechanisms of cancer. However, it is
      difficult to delineate them from the larger pool of genes that are deregulated in
      cancer (ie, passenger genes). In order to address this problem, we developed an
      approach called TRIAngulating Gene Expression (TRIAGE through clinico-genomic
      intersects). Here, we present a refinement of this approach incorporating a new
      scoring methodology to identify putative driver genes that are deregulated in
      cancer. TRIAGE triangulates - or integrates - three levels of information: gene
      expression, gene location, and patient survival. First, TRIAGE identifies regions
      of deregulated expression (ie, expression footprints) by deriving a newly
      established measure called the Local Singular Value Decomposition (LSVD) score
      for each locus. Driver genes are then distinguished from passenger genes using
      dual survival analyses. Incorporating measurements of gene expression and
      weighting them according to the LSVD weight of each tumor, these analyses are
      performed using the genes located in significant expression footprints. Here, we
      first use simulated data to characterize the newly established LSVD score. We
      then present the results of our application of this refined version of TRIAGE to
      gene expression data from five cancer types. This refined version of TRIAGE not
      only allowed us to identify known prominent driver genes, such as MMP1, IL8, and
      COL1A2, but it also led us to identify several novel ones. These results
      illustrate that TRIAGE complements existing tools, allows for the identification
      of genes that drive cancer and could perhaps elucidate potential future targets
      of novel anticancer therapeutics. 

PMID- 25949095
TI  - Elliptical Morphology of the Carpal Tunnel Cross Section.
AB  - Although the carpal tunnel is known for its anatomical constituents, its
      morphology is not well recognized. The aim of this study was to investigate the
      morphometric properties of the carpal tunnel and its surrounding structures.
      Magnetic resonance, cross-sectional images of the distal carpal tunnel were
      collected from eight cadaveric hands. Morphological analyses were performed for
      the cross sections of the carpal tunnel, interior carpus boundary, and exterior
      carpus boundary. The specimens had a carpal arch width and height of 23.9 +/- 2.9
      mm and 2.2 +/- 0.9 mm, respectively. The carpal tunnel, interior carpus boundary,
      and exterior carpus boundary had perimeters of 54.8 +/- 4.5 mm, 68.5 +/- 7.0 mm,
      and 130.6 +/- 11.8 mm, respectively, and areas of 183.5 +/- 30.1 mm2, 240.7 +/-
      40.2 mm2, and 1002.3 +/- 183.7 mm2, respectively. The cross sections were
      characterized by elliptical fitting with aspect ratios of 1.96 +/- 0.15, 1.96 +/-
      0.19, and 1.76 +/- 0.19 for the carpal tunnel, interior carpus boundary, and
      exterior carpus boundary, respectively. The major axis of the boundaries
      increased in pronation angle, relative to the hamate-trapezium axis, for the
      exterior carpus (6.0 +/- 3.0 degrees ), interior carpus (8.2 +/- 3.2 degrees ),
      and carpal tunnel (15.9 +/- 2.2 degrees ). This study advances our understanding
      of the structural anatomy of the carpal tunnel, and the morphological information
      is valuable in the identification of structural abnormality, assistance of
      surgical planning, and evaluation of treatment of effects.

PMID- 25949097
TI  - The consequences of mutations in the reproductive endocrine system.
AB  - The reproductive activity in male mammals is well known to be regulated by the
      hypothalamus-pituitary- gonad axis. The hypothalamic neurons secreting
      gonadotropin releasing hormone (GnRH) govern the reproductive neuroendocrine
      system by integrating all the exogenous information impinging on themselves. The
      GnRH synthesized and released from the hypothalamus arrives at the anterior
      pituitary through the portal vessels, provoking the production of the
      gonadotropins(follicle-stimulating hormone (FSH) and luteinizing hormone (LH)) at
      the same time. The gonadotropins affect the gonads to promote spermatogenesis and
      to secret testosterone. Testosterone acts on the GnRH neurons by a feedback loop
      through the circulatory system, resulting in the balance of all the hormones by
      regulating reproductive activities. These hormones exert their effects by acting
      on their own receptors, which are included in the signal transduction pathways as
      well. Unexpected aberrants are arised during this course of action of each
      hormone. This review summarizes these abnormal phenomena, including various
      mutations of molecules and their actions related to the reproductive function. 

PMID- 25949098
TI  - Nesfatin-1 as a new potent regulator in reproductive system.
AB  - Nesfatin-1 is a recently discovered anorexigenic peptide which is distributed in
      several brain areas implicated in the feeding and metabolic regulation. Recently,
      it has been reported that nesfatin-1 is expressed not only in brain, but also in
      peripheral organs such as digestive organs, adipose tissues, heart, and
      reproductive organs. Nesfatin-1 is markedly expressed in the pancreas, stomach
      and duodenum. Eventually, the nesfatin-1 expression in the digestive organs may
      be regulated by nutritional status, which suggests a regulatory role of
      peripheral nesfatin-1 in energy homeostasis. Nesfatin-1 is also detected in the
      adipose tissues of humans and rodents, indicating that nesfatin-1 expression in
      the fat may regulate food intake independently, rather than relying on leptin. In
      addition, nesfatin-1 is expressed in the heart as a cardiac peptide. It suggests
      that nesfatin-1 may regulate cardiac function and encourage clinical potential in
      the presence of nutrition-dependent physio-pathologic cardiovascular diseases.
      Currently, only a few studies demonstrate that nesfatin-1 is expressed in the
      reproductive system. However, it is not clear yet what function of nesfatin-1 is
      in the reproductive organs. Here, we summarize the expression of nesfatin-1 and
      its roles in brain and peripheral organs and discuss the possible roles of
      nesfatin-1 expressed in reproductive organs, including testis, epididymis, ovary,
      and uterus. We come to the conclusion that nesfatin-1 as a local regulator in
      male and female reproductive organs may regulate the steroidogenesis in the
      testis and ovary and the physiological activity in epididymis and uterus. 

PMID- 25949099
TI  - Modulation of neural circuit actvity by ethanol in basolateral amygdala.
AB  - Ethanol actions in the amygdala formation may underlie in part the reinforcing
      effects of ethanol consumption. Previously a physiological phenomenon in the
      basolateral amygdala (BLA) that is dependent on neuronal network activity,
      compound postsynaptic potentials (cPSPs) were characterized. Effects of acute
      ethanol application on the frequency of cPSPs were subsequently investigated.
      Whole cell patch clamp recordings were performed from identified projection
      neurons in a rat brain slice preparation containing the amygdala formation. Acute
      ethanol exposure had complex effects on cPSP frequency, with both increases and
      decreases dependent on concentration, duration of exposure and age of the animal.
      Ethanol produces complex biphasic effects on synaptically-driven network activity
      in the BLA. These findings may relate to subjective effects of ethanol on arousal
      and anxiolysis in humans. 

PMID- 25949100
TI  - Induction of Ovulation by Hormone Treatment in Ussurian Bullhead Leiocassis
      ussuriensis.
AB  - The effects of ovulation induction in ussurian bullhead, Leiocassis ussuriensis,
      were investigated by treating ussurian bullhead with hCG, LHRHa, GnRHa, ovaprim,
      and pimozide. hCG was injected to ussurian bullhead at 0.75% NaCl, 5,000, 10,000,
      20,000, and 30,000 IU, respectively. The ovulation inducement rates were 100% in
      20,000 and 30,000 IU. Fertilization rates were 82.7% and 79.8%. Hatching rates
      were 59.4% and 57.2%. Ovulation time was between 16-19 hr The concentrations of
      LHRHa injected were 0.75 NaCl, 50, 100, 200, 300, and 300 g/kg. The ovulation
      inducement rates were 100% in 300 and 400 ug/kg. Fertilization and hatching rates
      were 84.9% and 68.4% at 200 ug/kg. The times to ovulation were between 23 hr and
      34 hr. Ovaprim of 0.75% NaCl, 1.0, 1.5, 2.0, 2.5 and 3.0 ml/kg were injected to
      the abdominal cavity. The ovulation inducement rate was highest at 2.0 and 3.0
      ml/kg to 92% and ovulation time was between 27-38 hr. LHRHa concentrations of
      0.75% NaCl, 50, 100, 200, 300 and 400 ug were injected with pimozide (1,000 ug).
      Ovulation inducement rate was 100% from 200 to 400 IU with pimozide. Ovulation
      time was 22-36 h. Fertilization and hatching rates were 88.9% and 70.4% in 200
      ug/kg with pimozide. 

PMID- 25949101
TI  - Changes in Plasma Sex Steroid and Cortisol Levels during Annual Reproductive
      Cycle of Ribbed Gunnel, Dictyosoma burgeri.
AB  - We investigated the changes in plasma sex steroid hormones, testosterone (T),
      estradiol-17beta (E2), 17,20beta -dihydroxy-4-pregnen-3-one (17alpha20betaP), 11
      ketotestosterone (11KT) and cortisol levels from ribbed gunnel, Dictyosoma
      burgeri in associated with annual reproductive cycle. The gonadosomatic index
      (GSI) of females increased from November, peaked in February and decreased
      rapidly from March. The GSI of males also increased from November, peaked in
      January and then decreased gradually. In females, E2 levels increased and
      remained high from December to February. The levels of T showed a similar
      tendency and correlated (rs =0.898, p<0.01) with E2 levels. The levels of
      17alpha20betaP increased rapidly in February (4.78+/-1.01 ng/ml) and peaked in
      July (5.08+/-0.65 ng/ml). Cortisol level was peaked in March and correlated with
      17alpha20betaP levels (rs =0.696, p<0.01). In males, the levels of T was peaked
      in January and then decreased rapidly. The levels of 11KT were remained high from
      October to January. On the other hand, the levels of 17alpha20betaP fluctuated
      during reproductive cycle. These results suggest that plasma sex steroids in
      ribbed gunnels have annual periodicity, and that cortisol may involve in
      maturation of females. 

PMID- 25949102
TI  - Effect of TBT and PAHs on CYP1A, AhR and Vitellogenin Gene Expression in the
      Japanese Eel, Anguilla japonica.
AB  - Gene expressions of cytochrome P4501A (CYP1A), aryl hydrocarbon receptor (AhR)
      and vitellogenin (Vg) by endocrine disruptors, benzo[alpha]pyrene (B[a]P) and
      tributyltin (TBT) were examined in cultured eel hepatocytes which were isolated
      from eels treated previously with B[a]P (10 mg/kg) or estradiol-17beta (20 mg/kg)
      in vivo, and the relationship between CYP1A, AhR and Vg genes were studied. When
      the cultured eel hepatocytes were treated with B[a]P (10(-6)-10(-5) M) the gene
      expressions of CYP1A and AhR were enhanced in a concentration-dependent manner.
      However, when treated with TBT (10(-9)-10(-5) M) the gene expressions of CYP1A
      and AhR were suppressed at high concentrations (10(-6)-10(-5) M), while having no
      effects at low concentrations (10(-9)-10(-7) M). Gene expression of Vg was also
      suppressed by TBT in a concentration-dependent manner in cultured eel hepatocytes
      which was previously treated in vivo with estradiol-17beta. 

PMID- 25949103
TI  - Effect of manganese exposure on the reproductive organs in immature female rats.
AB  - Manganese (Mn(2+)) is a trace element that is essential for normal physiology,
      and is predominantly obtained from food. Several lines of evidence, however,
      demonstrated that overexposure to MnCl2 exerts serious neurotoxicity,
      immunotoxicity and developmental toxicity, particularly in male. The present
      study aimed to evaluate the effect of 0, 1.0, 3.3, and 10 mg/kg/day doses of
      MnCl2 on the reproductive organs in the immature female rats. Rats (PND 22; S.D.
      strain) were exposed to MnCl2 (MnCl2 ? 4H2O) dissolved in drinking water for 2
      weeks. The animals were sacrificed on PND 35, then the tissues were immediately
      removed and weighed. Histological studies were performed using the uteri tissue
      samples. Serum LH and FSH levels were measured with the specific ELISA kits. Body
      weights of the experimental group animals were not significantly different from
      those of control group animals. However, ovarian tissue weights in 1 mg and 3.3
      mg MnCl2 dose groups were significantly lower than those of control animals
      (p<0.05 and p<0.01, respectively). Uterine tissue weights of 3.3 mg dose MnCl2
      groups were significantly lower than those of control animals (p<0.01), while the
      1 mg MnCl2 dose and 10 mg MnCl2 dose failed to induce any change in uterine
      weight. Similarly, only 3.3 mg MnCl2 dose could induce the significant decrease
      in the oviduct weight compared to the control group (p<0.05). Non-reproductive
      tissues such as adrenal and kidney failed to respond to all doses of MnCl2
      exposure. The uterine histology revealed that the MnCl2 exposure could affect the
      myometrial cell proliferation particularly in 3.3 mg dose and 10mg dose group.
      Serum FSH levels were significantly decreased in 1mg MnCl2 dose and 10 MnCl2 mg
      groups (p<0.05 and p<0.01, respectively). In contrast, treatment with 1 mg MnCl2
      dose induced a significant increment of serum LH level (p<0.05). The present
      study demonstrated that MnCl2 exposure is capable of inducing abnormal
      development of reproductive tissues, at least to some extent, and altered
      gonadotropin secretions in immature female rats. Combined with the well-defined
      actions of this metal on GnRH and prolactin secretion, one can suggest the Mn(2+)
      might be a potential environmental mediator which is involved in the female
      pubertal process. 

PMID- 25949104
TI  - Differential Expression Patterns of Crystallin Genes during Ocular Development of
      Olive Flounder (Paralichthys olivaceus).
AB  - Olive flounder Paralichthys olivaceus is one of the most widely cultured fish
      species in Korea. Although olive flounder receive attention from aquaculture and
      fisheries and extensive research has been conducted eye morphological change in
      metamorphosis, but little information was known to molecular mechanism and gene
      expression of eye development- related genes during the early part of eye
      formation period. For the reason of eyesight is the most important sense in
      flounder larvae to search prey, the screening and identification of expressed
      genes in the eye will provide useful insight into the molecular regulation
      mechanism of eye development in olive flounder. Through the search of an olive
      flounder DNA database of expressed sequence tags (EST), we found a partial
      sequence that was similar to crystallin beta A1 and gamma S. Microscopic
      observation of retinal formation correspond with the time of expression of the
      crystallin beta A1 and gamma S gene in the developmental stage, these result
      suggesting that beta A1 and gamma S play a vital role in the remodeling of the
      retina during eye development. The expression of crystallin beta A1 and gamma S
      were obviously strong in eye at all tested developing stage, it is also
      hypothesized that crystallin acts as a molecular chaperone to prevent protein
      aggregation during maturation and aging in the eye. 

PMID- 25949105
TI  - The Morphological Study of Wild and Farmed Olive Flounder (Paralichthys
      olivaceus): The Role of Indirect Selection within and between Populations.
AB  - This study was conducted to analyze the difference of body types within and
      between wild and farmed populations of olive flounder Paralichthys olivaceus
      using measured records of morphological traits. The results showed that surveyed
      traits and standard deviation were 1,355+/-742 g of body weight, 48.01+/-7.79 cm
      of total length, and 40.96+/-6.80 cm of body length. Also body height, body shape
      index and condition factor were 17.19+/-3.43 cm, 9.99+/-0.74 and 11.16+/-1.54,
      respectively. As result of least squares mean and standard error for each trait
      assumed in this study, those of farmed population showed significantly higher
      than those of wild population in all traits, exclusively in total length and body
      length (p<0.01). Particularly, the values of the body height and the body weight
      of the farmed population were higher than those of the wild population in the
      same total length. And the phenotypic correlation coefficients of the body
      weight, the total length, the body length and the body height showed strong
      positive correlation in all populations. These result suggested that
      morphological differences exist in farmed and wild flounder. Therefore,
      introduction of wild flounder is essential for the future production to improve
      the body type of farmed flounder, and parental fish should be chosen by
      considering selection of commercially important traits in the production process.

PMID- 25949106
TI  - Geographic Variations and Genetic Distance of Three Geographic Cyclina Clam
      (Cyclina sinensis Gmelin) Populations from the Yellow Sea.
AB  - The gDNA isolated from Cyclina sinensis from Gochang (GOCHANG), Incheon (INCHEON)
      and a Chinese site (CHINESE), were amplified by PCR. Here, the seven
      oligonucleotide decamer primers (BION-66, BION-68, BION-72, BION-73, BION-74,
      BION-76, and BION-80) were used to generate the unique shared loci to each
      population and shared loci by the three cyclina clam populations. As regards
      multiple comparisons of average bandsharing value results, cyclina clam
      population from Chinese (0.763) exhibited higher bandsharing values than did clam
      from Incheon (0.681). In this study, the dendrogram obtained by the seven decamer
      primers indicates three genetic clusters: cluster 1 (GOCHANG 01~ GOCHANG 07),
      cluster 2 (INCHEON 08~INCHEON 14), cluster 3 (CHINESE 15~CHINESE 21). The
      shortest genetic distance that displayed significant molecular differences was
      between individuals 15 and 17 from the Chinese cyclina clam (0.049), while the
      longest genetic distance among the twenty-one cyclina clams that displayed
      significant molecular differences was between individuals GOCHANG no. 03 and
      INCHEON no. 12 (0.575). Individuals of Incheon cyclina clam population was
      somewhat closely related to that of Chinese cyclina clam population. In
      conclusion, our PCR analysis revealed a significant genetic distance among the
      three cyclina clam populations. 

PMID- 25949107
TI  - Temperature-dependent Index of Mitotic Interval (tau0) for Chromosome
      Manipulation in Korean Bullhead, Pseudobagrus fulvidraco.
AB  - Korean bullhead (Pseudobagrus fulvidraco) was collected from the Kum River areas
      of Kangkyung-eup, Nonsan city, Chungcheongnam-do, Korea, from April to June, 2012
      and was fertilized in order to observe egg development and temperature-related
      cleavage rates and mitotic intervals (tau0). The fertilized eggs were separative,
      demersal and light yellowish with 1.5+/-0.06 mm in diameter, and did not contain
      oil globules. The first cleavage stages were 90 min, 80 min, 60 min and 50 min at
      21 degrees C , 24 degrees C , 27 degrees C and 30 degrees C , respectively. At
      higher temperatures, eggs developed faster and underwent further identical
      development. For Korean bullhead, tau0 were 33.4+/-2.08 min at 21 degrees C,
      31.5+/-3.06 min at 24 degrees C, 28.1+/-2.11 min at 27 degrees C and 26.4+/-3.35
      min at 30 degrees C . There were strong negative correlations between the tau0
      and water temperatures at all points studied (Y= 1.13X+58.15, R (2)=0.98, n=30,
      where Y is tau0 and X is temperature). The results obtained in this work will be
      helpful for chromosome manipulation by use of cleavage frequency data and tau0
      data in Korean bullhead. 

PMID- 25949108
TI  - Decreased contact inhibition in mouse adipose mesenchymal stem cells.
AB  - The proliferation of embryonic cells or adult stem cells in tissue is critically
      regulated during development and repair. How limited the proliferation of cells,
      so far, is not much explored. Cell-cell contact proliferation inhibition is known
      as a crucial mechanism regulating cell proliferation in vitro and in vivo. In
      this study we examined the characters of mouse subcutaneous adipose derived stem
      cells (msADSC) whether they lost or get contact inhibition during in vitro
      culture. The characters of msADSC growth after confluence were analyzed using
      confocal microscope and the expression profiles of contact inhibition related
      genes were analyzed according to the morphological changes using real-time PCR
      method. msADSC showed overlapping growth between them but not after passage 14.
      The cell shapes were also changed after passage 14. The expression profiles of
      genes which are involved in contact inhibition were modified in the msADSC after
      passage 14. The differentiation ability of msADSCs to adipocyte, chondrocyte and
      osteocyte was not changed by such changes of gene expression profiles. Based on
      these results, it is revealed that smADSC were characterized by getting of strong
      cell-cell contact inhibition after passage 14 but the proliferation and
      developmental ability were not blocked by the change of cell-cell contact
      proliferation inhibition. These finding will help to understand the growth of
      adipose tissue, although further studies are needed to evaluate the physiological
      meaning of the cell-cell contact proliferation inhibition during in vitro culture
      of msADSC. 

PMID- 25949109
TI  - Aggregation of Human Eyelid Adipose-derived Stem Cells by Human Body Fluids.
AB  - Fetal bovine serum (FBS) is the most frequently used serum for the cultivation of
      mammalian cells. However, since animal-derived materials might not be appropriate
      due to safety issues, allogeneic human serum (HS) has been used to replace FBS,
      particularly for the culture of human cells. While there has been a debate about
      the advantages of HS, its precise effect on human adult stem cells have not been
      clarified. The present study aimed to investigate the effect of HS on the human
      eyelid adipose stem cells (HEACs) in vitro. When HEACs were cultivated in a
      medium containing 10% HS, many cells moved into several spots and aggregated
      there. The phenomenon was observed as early as 9 days following 10% HS treatment,
      and 12 days following 5% HS plus 5% FBS treatment. However, the aggregation was
      never observed when the same cells were cultivated with 10% FBS or bovine serum
      albumin. To examine whether cell density might affect the aggregation, cells were
      seeded with different densities on 12-well dish. Until the beginning of
      aggregation, cells seeded at low densities exhibited the longest culture period
      of 16 days whereas cells seeded at high densities showed the shortest period of 9
      days to form aggregation. The number of cells was 15.1+/-0.2*10(4) as the least
      for the low density group, and 29.3+/-2.8*10(4) as the greatest for the high
      density group. When human cord blood serum or normal bovine serum was examined
      for the same effect on HEACs, interestingly, cord blood serum induced the
      aggregation of cells whereas bovine serum treatment has never induced. When cells
      were cultivated with 10% HS for 9 days, they were obtained and analyzed by RT
      PCR. Compared to FBS-cultivated HEACs, HS-cultivated HEACs did not express VIM,
      and less expressed GATA4, PALLD. On the other hand, HS-cultivated HEACs expressed
      MAP2 more than FBS-cultivated HEACs. In conclusion, human adult stem cells could
      move and form aggregates by the treatment with human body fluids. 

PMID- 25949110
TI  - Chromosomal Modification in Human Embryonic Stem Cells Cultured in a Feeder-Free
      Condition after Single Cell Dissociation using Accutase.
AB  - Human embryonic stem (ES) cells are a potential source of cells for developmental
      studies and for a variety of applications in transplantation therapies and drug
      discovery. However, human ES cells are difficult to culture and maintain at a
      large scale, which is one of the most serious obstacles in human ES cell
      research. Culture of human ES cells on MEF cells after disassociation with
      accutase has previously been demonstrated by other research groups. Here, we
      confirmed that human ES cells (H9) can maintain stem cell properties when the
      cells are passaged as single cells under a feeder-free culture condition.
      Accutase-dissociated human ES cells showed normal karyotype, stem cell marker
      expression, and morphology. We prepared frozen stocks during the culture period,
      thawed two of the human ES cell stocks, and analyzed the cells after culture with
      the same method. Although the cells revealed normal expression of stem cell
      marker genes, they had abnormal karyotypes. Therefore, we suggest that accutase
      dissociated single cells can be usefully expanded in a feeder-free condition but
      chromosomal modification should be considered in the culture after freeze
      thawing. 

PMID- 25949111
TI  - Ectopic Expression of Cenexin1 S796A Mutant in ODF2(+/-) Knockout Background
      Causes a Sperm Tail Development Defect.
AB  - The outer dense fiber 2 (ODF2) protein is an important component of sperm tail
      outer dense fiber and localizes at the centrosome. It has been reported that the
      RO072 ES cell derived homozygote knock out of ODF2 results in an embryonic lethal
      phenotype, and XL169 ES cell derived heterozygote knock out causes severe defects
      in sperm tail development. The ODF2s splicing variant, Cenexin1, possesses a C
      terminal extension, and the phosphorylation of serine 796 residue in an extended
      C-terminal is responsible for Plk1 binding. Cenexin1 assembles ninein and causes
      ciliogenesis in early stages of the cell cycle in a Plk1-independent manner.
      Alternatively, in the late stages of the cell cycle, G2/M phase, Cenexin1 binds
      to Plk1 and results in proper mitotic progression. In this study, to identify the
      in vivo function of Plk1 binding to phosphorylated Cenexin1 S796 residue, and to
      understand the in vivo functional differences between ODF2 and Cenexin1, we
      generated ODF2/Cenexin1 S796A/Cenexin1 WT expressing transgenic mice in a RO072
      ES cell derived ODF2(+/-) knock out background. We observed a severe defect of
      sperm tail development by ectopic expression of Cenexin1 S796A mutant and no
      phenotypic differences between the ectopic expression of ODF2/Cenexin1 WT in
      ODF2(+/-) background and in normal wild type mice. 

PMID- 25949112
TI  - The ascidian numb gene involves in the formation of neural tissues.
AB  - Notch signaling plays fundamental roles in various animal development. It has
      been suggested that Hr-Notch, a Notch homologue in the ascidian Halocynthia
      roretzi, is involved in the formation of peripheral neurons by suppressing the
      neural fates and promoting the epidermal differentiation. However, roles of Notch
      signaling remain controversial in the formation of nervous system in ascidian
      embryos. To precisely investigate functions of Notch signaling, we have isolated
      and characterized Hr-Numb, a Numb homologue which is a negative regulator of
      Notch signaling, in H. roretzi. Maternal expression of Hr-Numb mRNAs was detected
      in egg cytoplasm and the transcripts were inherited by the animal blastomeres.
      Its zygotic expression became evident by the early neurula stage and the
      transcripts were detected in dorsal neural precursor cells. Suppression of Hr
      Numb function by an antisense morpholino oligonucleotide resulted in larvae with
      defect in brain vesicle and palps formation. Similar results have been obtained
      by overexpression of the constitutively activated Hr-Notch forms. Therefore,
      these results suggest that Hr-Numb is involved in Notch signaling during ascidian
      embryogenesis. 

PMID- 25949113
TI  - Identification and Characterization of LHX8 DNA Binding Elements.
AB  - Lhx8 (LIM homeobox 8) gene encodes a LIM homeodomain transcriptional regulator
      that is preferentially expressed in germ cells and critical for mammalian
      folliculogenesis. However, Lhx8 DNA binding sequences are not characterized yet.
      We aimed to identify and characterize a cis-acting sequence of germ-cell specific
      transcriptional factor, Lhx8. To identify Lhx8 DNA binding element, Cyclic
      Amplification of Sequence Target (CAST) Analysis was performed. Electrophoretic
      Mobility Shift Assay (EMSA) was processed for the binding specificity of Lhx8.
      Luciferase assay was for the transcriptional activity of Lhx8 through identified
      DNA binding site. We identified a putative cis-acting sequence, TGATTG as Lhx8
      DNA binding element (LBE). In addition, Lhx8 binds to the LBE with high affinity
      and augments transcriptional activity of luciferase reporter driven by artificial
      promoter containing the Lhx8 binding element. These findings indicate that Lhx8
      directly regulates the transcription of genes containing Lhx8 binding element in
      oocytes during early folliculogenesis. 

PMID- 25949114
TI  - Sex Ratio and Sex Reversal in Two-year-old Class of Oyster, Crassostrea gigas
      (Bivalvia: Ostreidae).
AB  - The sex ratio (F:M) in the same population of oyster, Crassostrea gigas at the
      commencement of the study (2007) was 1:1.0, but changed to 1:2.8 by the end of
      the study (2008). The sex reversal rate in two-year-old oysters was 40.2%.
      Specifically, female to male sex reversal rate was 66.1%, which is higher than
      the male to female sex reversal rate of 21.1%. The sex reversal pattern of C.
      gigas appears to go from male=>female=>male, and as such is determined to be
      rhythmical hermaphroditism. 

PMID- 25949115
TI  - Mammary gland-specific expression of biologically active human osteoprotegerin in
      transgenic mice.
AB  - Osteoprotegerin (OPG) is a secreted glycoprotein that regulates bone resorption
      by inhibiting differentiation and activation of osteoclast, thereby potentially
      useful for the treatment of many bone diseases associated with increased bone
      loss. In this study, we designed a novel cDNA expression cassette by modifying
      the potent and mammary gland-specific goat beta-casein/hGH hybrid gene construct
      and examined human OPG (hOPG) cDNA expression in transgenic mice. Six transgenic
      mice all successfully expressed hOPG in their milk at the level of 0.06-2,000
      ug/ml. An estimated molecular weight of the milk hOPG was 55 kDa in SDS-PAGE,
      which is the same as a naturally glycosylated monomer. This hOPG expression was
      highly specific to the mammary glands of transgenic mice. hOPG mRNA was not
      detected in any organs analyzed except mammary gland. Functional integrity of
      milk hOPG was evaluated by TRAP (tartrate-resistant acid phosphatase) activity
      assay in bone marrow cell cultures. OPG ligand (OPG-L) treatment increased TRAP
      activity by two fold but it was completely abolished by co-treatment with
      transgenic milk containing hOPG. Taken together, our novel cDNA expression
      cassette could direct an efficient expression of biologically active hOPG, a
      potential candidate pharmaceutical for bone diseases, only in the mammary gland
      of transgenic mice. 

PMID- 25949116
TI  - Regulation of Pluripotency-related Genes and Differentiation in Mouse Embryonic
      Stem Cells by Direct Delivery of Cell-penetrating Peptide-conjugated CARM1
      Recombinant Protein.
AB  - Coactivator-associated arginine methyltransferase 1 (CARM1) is included in the
      protein arginine methyltransferase (PRMT) family, which methylates histone
      arginine residues through posttranslational modification. It has been proposed
      that CARM1 may up-regulate the expression of pluripotency-related genes through
      the alteration of the chromatin structure. Mouse embryonic stem cells (mESCs) are
      pluripotent and have the ability to self-renew. The cells are mainly used to
      study the genetic function of novel genes, because the cells facilitate the
      transmission of the manipulated genes into target mice. Since the up-regulated
      methylation levels of histone arginine residue lead to the maintenance of
      pluripotency in embryos and stem cells, it may be suggested that CARM1
      overexpressing mESCs elevate the expression of pluripotency-related genes in
      reconstituted embryos for transgenic mice and may resist the differentiation into
      trophectoderm (TE). We constructed a fusion protein by connecting CARM1 and 7X
      arginine (R7). As a cell-penetrating peptide (CPP), can translocate CARM1 protein
      into mESCs. CPP-CARM1 protein was detected in the nuclei of the mESCs after a
      treatment of 24 hours. Accordingly, the expression of pluripotency-related genes
      was up-regulated in CPP-CARM1-treated mESCs. In addition, CPP-CARM1-treated mESC
      derived embryoid bodies (EBs) showed an elevated expression of pluripotency
      related genes and delayed spontaneous differentiation. This result suggests that
      the treatment of recombinant CPP-CARM1 protein elevates the expression of
      pluripotency-related genes of mESCs by epigenetic modification, and this protein
      delivery system could be used to modify embryonic fate in reconstituted embryos
      with mESCs. 

PMID- 25949117
TI  - Decreased Expression of Inhibitor of DNA-binding (Id) Proteins and Vascular
      Endothelial Growth Factor and Increased Apoptosis in Ovarian Aging.
AB  - This study examined the expression of inhibitor of DNA-binding (Id) proteins and
      vascular endothelial growth factor (VEGF) in the ovary according to female age
      using a mice model as the first step in investigating the potential role of Ids
      and VEGF in ovarian aging. C57BL inbred female mice of three age groups (6-9, 14
      16, and 23-26 weeks) were injected with 5 IU pregnant mare's serum gonadotropin
      (PMSG) in order to synchronize the estrus cycle. After 48 h, ovarian expression
      of Ids and VEGF was analyzed by reverse transcriptase-polymerase chain reaction
      (RT-PCR), western blot and immunohistochemistry. Ovarian apoptosis was examined
      by ovarian expression of Bcl-2 and Bcl-xL. Expression of Id-1 and VEGF was
      decreased with advancing female age, but not Id-2, Id-3, and Id-4. In particular,
      their expressions were significantly decreased in aged mice of 23-26 weeks
      compared with the young mice of 6-9 weeks (p < 0.05). In contrast, ovarian
      apoptosis was greatly increased in the aged mice compared to the young mice. This
      result suggests that Id-1 may have an implicated role in ovarian aging by
      associating with VEGF. 

PMID- 25949118
TI  - The Effects of Female Shell Size on Reproductive Potential of the Egg Capsule in
      Rapa Whelk Rapana venosa in Three Regions of Different Salinities.
AB  - We investigated the effects of shell height on reproductive potential of the
      female Rapana venosa in three regions of different salinities (the coastal zone
      of the Gwangyang Bay (S-1); the upper reaches (S-3); lower reaches (S-2) of the
      Seomjin River). The number of egg capsules, egg capsule height, and fecundity
      associated with reproductive potential of larger female rapa whelks were higher
      than those of smaller individuals in all three regions. Correlation analyses
      showed that there is a significant positive correlation between egg capsule and
      female shell height. Mean of shell heights, egg capsule heights, the number of
      egg capsules in an egg mass, and fecundity in an egg capsule produced from female
      individuals inhabiting S-1 region were markedly higher than those inhabiting S-2
      and S-3 regions. In particular, the fecundity of the rapa whelk increased with
      the salinity and shell height. Although large rapa whelks produced a large number
      of egg capsules at S-1 region, those at S-3 habitat laid less egg capsules with
      smaller size. If these rapa whelks were put into S-2 region, the number of egg
      capsules produced by a female at S-2 region was slightly larger than those
      produced by a female at S-3 region. This provides a clear evidence that the
      number of the egg capsules can be controlled by the salinity. In the coastal zone
      of the Gwangyang Bay and the upper reaches of Seomjin River, the fecundity of
      this species was estimated to be approximately 182,000-1,302,000 eggs/ind./yr. 

PMID- 25949119
TI  - The Effects of Cynomorium songaricum on the Reproductive Activity in Male Golden
      Hamsters.
AB  - Cynomorium songaricum (CS) has been used in traditional Korean medicine in
      treating male impotence and sexual dysfunction. We investigated the effects of
      aqueous CS extract on the reproductive activity of golden hamsters whose
      spermatogenetic capacity is active in summer and inactive in winter. The animals
      were divided into 5 groups: long photoperiod (LP) control, short photoperiod (SP)
      control, and SP animals treated with low, middle, or high concentrations of CS.
      The animals were orally ingested with low (0.5 g/kg), middle (1.0 g/kg), or high
      (2.5 g/kg) concentrations of the aqueous extracts for 8 weeks on the daily basis.
      The control animals received the vehicle. As results, the LP control animals
      showed active testicular function but SP control animals displayed remarkably
      reduced testicular weights. The outcomes of the reproductive activity from low
      and middle concentrations of CS treatments were identical and marked as low dose.
      The consequences were a partial blocking of regressing activity by SP. On the
      other hand, the animals treated with high dose of CS extract showed remarkable
      significance in comparison to the SP control, indicative of a complete blocking
      effect of the CS on the regressing testes by SP. There were a dose-dependent
      effects of the CS on the sexual function. These results suggest that the CS
      extract promotes the male fertility by strengthening the spermatogenesis in the
      golden hamsters. 

PMID- 25949120
TI  - The Expression Pattern of Melatonin Receptor 1a Gene during Early Life Stages in
      the Nile tilapia (Oreochromis niloticus).
AB  - The action of melatonin within the body of animals is known to be mediated by
      melatonin receptors. Three different types of melatonin receptors have been
      identified so far in fish. However, which of these are specifically involved in
      puberty onset is not known in fish. We cloned and analyzed the sequence of
      melatonin receptor 1a (mel 1a) gene in Nile tilapia Oreochromis niloticus. In
      addition, we examined the tissue distribution of gene expressions for three types
      of receptors, mel 1a, 1b and lc and investigated which of them is involved in the
      onset of puberty by comparing their expression with that of gonadotropin
      releasing hormone receptor I (GnRHr I) gene using quantitative real-time PCR from
      1 week post hatch (wph) to 24 wph. The mel 1a gene of Nile tilapia consisted of
      two exons and one bulky intron between them. Mel 1a gene was found to be highly
      conserved gene showing high homology with the corresponding genes from different
      teleost. All three types of melatonin receptor genes were expressed in the brain,
      eyes and ovary in common. Expression of mel 1a gene was the most abundant and
      ubiquitous among 3 receptors in the brain, liver, gill, ovary, muscle, eye,
      heart, intestine, spleen and kidney. Mel 1b and mel 1c genes were, however,
      expressed in fewer tissues at low level. During the development post hatch,
      expressions of both mel 1a and GnRHr I genes significantly increased at 13 wph
      which was close to the putative timing of puberty onset in this species. These
      results suggest that among three types of receptors mel 1a is most likely
      associated with the action of melatonin in the onset of puberty in Nile tilapia. 

PMID- 25949121
TI  - Characterization of Pubertal Development Phases in Female Longtooth Grouper,
      Epinephelus bruneus via Classification of Bodyweight.
AB  - Puberty is the developmental period which animals obtain the ability of
      reproducing sexually for the first time in life. In commercially important
      aquaculture fish species, the onset of puberty is a matter of major interest due
      to controlling of sexual maturation to improve broodstock management. To
      investigate pubertal characteristics of female longtooth grouper (Epinephelus
      bruneus), specimens were classified into three groups by the bodyweight,
      including 1, 2, and 3 kg group. Thereafter, we focused on ovarian development and
      level changes of endocrine regulation factors (GnRH, GTHs, steroid hormone). In
      the non-breeding season (April), the levels of endocrine regulation factors
      showed increasing trends in accordance with bodyweight gaining; nevertheless, the
      oocytes were growth phase belongs to almost peri-nucleous stages in all groups.
      In the breeding season (June), the levels of endocrine regulation factors were
      fluctuated that decreases in levels of sbGnRH and FSHbeta mRNA expressions along
      with serum E2 concentrations in 3 kg of group. However, LHbeta mRNA expression
      levels sustained increasing trends by the bodyweight. Moreover, the oocytes
      developed that 2 kg and 3 kg groups obtained plentiful vitellogenic oocytes while
      1 kg group was still composed with greater part of pre-vitellogenic oocytes.
      Especially, the oocytes of 3 kg group reached over 450 MUm of diameters that
      indicating possibility to enter the final maturations. These results suggest that
      the progress of pubertal development in female E. bruneus could be classify into
      three phases via bodyweight, including pre-puberty (1 kg), early-puberty (2 kg)
      and puberty (3 kg). 

PMID- 25949122
TI  - RNA Polymerase II Inhibitor, alpha-Amanitin, Affects Gene Expression for Gap
      Junctions and Metabolic Capabilities of Cumulus Cells, but Not Oocyte, during in
      vitro Mouse Oocyte Maturation.
AB  - A specific inhibitor of RNA polymerase II, alpha-amanitin is broadly used to
      block transcriptional activities in cells. Previous studies showed that alpha
      amanitin affects in vitro maturation of cumulus-oocyte-complex (COC). In this
      study, we evaluated the target of alpha-amanitin, and whether it affects oocytes
      or cumulus cells (CCs), or both. We treated alpha-amanitin with different time
      period during in vitro culture of denuded oocytes (DOs) or COCs in comparison,
      and observed the changes in morphology and maturation status. Although DOs did
      not show any change in morphology and maturation rates with alpha-amanitin
      treatment, oocytes from COCs were arrested at metaphase I (MI) stage and CCs were
      more scattered than control groups. To discover causes of meiotic arrest and
      scattering of CCs, we focused on changes of cumulus expansion, gap junctions, and
      cellular metabolism which to be the important factors for the successful in vitro
      maturation of COCs. Expression of genes for cumulus expansion markers (Ptx3,
      Has2, and Tnfaip6) and gap junctional proteins (Gja1, Gja4, and Gjc1) decreased
      in alpha-amanitin-treated CCs. However, these changes were not observed in
      oocytes. In addition, expression of genes related to metabolism (Prps1, Rpe,
      Rpia, Taldo1, and Tkt) decreased in alpha -amanitin-treated CCs but not in
      oocytes. Therefore, we concluded that the transcriptional activities of CCs for
      supporting suitable transcripts, especially for its metabolic activities and
      formation of gap junctions among CCs as well as with oocytes, are important for
      oocytes maturation in COCs. 

PMID- 25949123
TI  - Intersexuality of Scomberomorus niphonius from the Coastal Area around Jeju
      Island, Korea (Teleostei: Scombridae).
AB  - This study histologically describes the intersexuality of Scomberomorus niphonius
      collected from the coastal area near Jeju Island. A total of 126 S. niphonius,
      collected from March to July 2012 with a total length of 62.4 cm (+/-17.5) and a
      total weight of 1,701.9 g (+/-1,528.9) were used for analyses. From a
      histological perspective, two types of intersex were confirmed. One type had
      scattered germ cells from the opposite sex within the gonad. The second type
      developed germ cells from the opposite sex in the connective tissue of the outer
      gonadal membrane. The intersexuality was 14.3% (n=18/126), with females (21.3%;
      n=16/75) exhibiting a higher rate than males (3.9%; n=2/51). There was no
      displayed correlation between intersexuality and the total length and weight. 

PMID- 25949124
TI  - Sex Reversal and Masculinization according to Growth in Longtooth Grouper
      Epinephelus bruneus.
AB  - To understand the sex reversal characteristics in the longtooth grouper
      (Epinephelus bruneus), this study examined the sex reversal and artificial
      masculinization of wild caught E. bruneus reared in indoor rearing tank after a
      17alpha-methyltestosterone injection. To domesticate a broodstock, 64 wild caught
      E. bruneus, between 47.0 to 110.0 cm in total length and from 1.5 to 21.4 kg in
      body weight, were reared in indoor rearing tank (4.0 to 5.0 m wide, and 2.5 to
      3.0 m depth) for four years. Seven specimens showed sex reversal from female to
      male during indoor rearing condition, whose total length and body weights were
      from 63.0 to 99.0 cm and from 4.4 to 13.2 kg, respectively. After inducing
      artificial masculinization in 14 female E. bruneus with a 17alpha
      methyltestosterone (2.0 mg/kg BW) implants for 3 years, spermiation occurred in 9
      specimens (total length: 54.0 to 68.0 cm, body weight: 2.3 to 4.3 kg). Among the
      female to male sex reversals, two specimens returned back to being female, whose
      body weights were 2.8 kg (initially 2.6 kg) and 2.7 kg (initially 2.3 kg).
      Therefore, this study suggested that E. bruneus (> 3.0 kg) was more effective in
      masculinizing by 17alpha-methyltestosterone implants. 

PMID- 25949125
TI  - Seminiferous Epithelium Cycle and Developmental Stages of Spermatids in the
      Clethrionomys rufocanus.
AB  - The seminiferous epithelium cycle and developmental stages of spermatids in
      Clethrionomys rufocanus were observed under a light microscope. The seminiferous
      epithelium cycle was divided into 8 stages. Type Ad spermatogonia appeared
      through all stages. Type Ap, In, and B spermatogonia appeared in stages I, II,
      III, and IV. In the first meiosis prophase, the leptotene spermatocytes appeared
      from stage V, the zygotene spermatocytes in stages I, VI, VII, VIII, the
      pachytene spermatocytes from stages II to VI, the diplotene spermatocytes in
      stage VII. The meiotic figures and interkinesis spermatocytes were observed in
      stage VIII. Developing spermatids were subdivided into 10 steps, based on the
      morphological characteristics such as the acrosome formation changes in
      spermatozoa, nucleus, cytoplasm, and spermiation changes. The C. rufocanus
      spermatocytogenesis and spermiogenesis results displayed similar results with
      Apodemus agrarius coreae and A. speciosus peninsulae. Considering all the
      results, the spermatogenesis may be useful information to analyze the
      differentiation of spermatogenic cells and the breeding season. 

PMID- 25949126
TI  - Effect of Immortalization-Upregulated Protein-2 (IMUP-2) on Cell Death of
      Trophoblast.
AB  - Trophoblasts, in the placenta, play a role for placental development as well as
      implantation in the early pregnancy. The characteristics and functions of
      trophoblast are identified by their localization and potency for proliferation,
      differentiation, and invasion. Thus, inadequate trophoblast cell death induces
      trophoblast dysfunction resulting in abnormal placental development and several
      gynecological diseases. Recently, it was reported that increased immortalization
      upregulated protein-2 (IMUP-2) by hypoxia influences trophoblast apoptosis.
      However, IMUP-2 function on autophagy, which is type II programmed cell death
      remains unclear. In this study, we analyzed IMUP-2 expression in trophoblast
      cells (HTR8-SVneo) and compared IMUP-2 effects on cell death including apoptosis
      and autophagy in trophoblast regardless of IMUP-2 expression. Increased IMUP-2 in
      trophoblast by IMUP-2 gene transfection induces cell death, especially, apoptosis
      increases more than autophagy (p<0.05). However, the decreased IMUP-2 in
      trophoblasts after siRNA treatment decreased apoptosis with the decreased
      activities of caspase 3 and 7. The expressions of LC3 and MDC as an autophagosome
      makers and phosphorylated mTOR, which is a negative regulator for autophagy,
      increased. In addition, the S phase of cell cycle increased in trophoblasts when
      IMUP-2 expression decreased. Taken together, the alteration of IMUP-2 can control
      the balance between apoptosis and autophagy of trophoblasts resulting in
      functional involvement in placental development and in gynecological diseases by
      regulating the function of trophoblasts. 

PMID- 25949127
TI  - Continuous melatonin attenuates the regressing activities of short photoperiod in
      male golden hamsters.
AB  - Golden hamsters reproduce in a limited time of a year. Their sexual activities
      are active in summer but inactive in winter during which day length does not
      exceed night time and environmental conditions are severe to them. The
      reproductive activities are determined by the length of light in a day
      (photoperiod). Melatonin is synthesized and secreted only at night time from the
      pineal gland. Duration of elevated melatonin is longer in winter than summer,
      resulting in gonadal regression. The present study aimed at the influences of
      continuous melatonin treatments impinging on the gonadal function in male golden
      hamsters. Animals received empty or melatonin-filled capsules for 10 weeks. They
      were divided into long photoperiod (LP) and short photoperiod (SP). All the
      animals maintained in LP (either empty or melatonin-filled capsules) showed large
      testes, implying that melatonin had no effects on testicular functions. Animals
      housed in SP displayed completely regressed testes. But animals kept in SP and
      implanted with melatonin capsules exhibited blockage of full regression by SP.
      These results suggest that constant release of melatonin prohibits the regressing
      influence of SP. 

PMID- 25949128
TI  - Ultrastructural Characteristics of the Testis, Spermatogenesis and Taxonomic
      Values of Sperm Morphology in Male Ruditapes philippinarum in Western Korea.
AB  - Ultrastructural characteristics of the germ cells and accessory cells in testis
      during spermatogenesis and taxonomic values of mature sperm morphology of
      Ruditapes philippinarum were investigated by the transmission electron microscope
      and scanning electron microscope observations. The testis is the diffuse organ
      that consists of branching acini containing developing germ cells and accessory
      cells associated with spermatogenesis. The morphology of the spermatozoon is of
      the primitive type and is somewhat different to those of other bivalves. The
      morphologies of the sperm nucleus type and the acrosome shape of this species
      have a cylinderical type and a modified cone shape, respectively. As some
      ultrastructural characteristics of the acrosomal vesicle, the peripheral parts of
      two basal rings show electron opaque part, while the apex part of the acrosome
      shows electron lucent part. These characteristics of sperm belong to the family
      Veneridae in the subclass Heterodonta, unlike a characteristic of the subclass
      Pteriomorphia showing all part of the acrosome being composed of electron opaque
      part. In particular, a cylinder-like nucleus of the sperm is curved. The
      spermatozoon is approximately 48-51 MUm in length, including a long acrosome
      (about 2.40 MUm in length), a curved sperm nucleus (about 3.40 MUm in length),
      and a tail flagellum. The axoneme of the sperm tail shows a 9+2 structure. 

PMID- 25949129
TI  - Cathepsin B in eutopic and ectopic endometrial tissues of patients with
      endometriosis.
AB  - This study was performed to investigate the expression of cathepsin B mRNA and
      protein in eutopic and ectopic endometrial tissues of patients with endometriosis
      and in normal endometrial tissues and to clarify the association between the
      cathepsin B expression and endometriosis. A total of 40 women with histologically
      confirmed endometriosis were recruited for study group. For controls, 20 women
      undergoing operative treatment for uterine myoma, cervical intraepithelial
      neoplasia (CIN) or benign gynecologic conditions other than endometriosis were
      recruited. Eutopic endometrial tissues of both groups and ectopic endometrial
      tissue of study group were collected during the operations. We employed real time
      reverse transcriptase - polymerase chain reaction (RT-PCR) to quantify mRNA
      levels of cathepsin B in these tissues. Then, we performed western blot analysis
      to measure the protein levels of cathepsin B. The expressions of cathepsin B mRNA
      and protein were significantly higher in both eutopic and ectopic endometrial
      tissues of women with endometriosis than in endometrial tissues of controls.
      These data suggest that the higher expression of cathepsin B in the endometrial
      tissues might be associated with the development of endometriosis. In addition,
      eutopic endometrium itself with higher expression cathepsin B may play a pivotal
      role in the histogenesis of endometriosis. 

PMID- 25949130
TI  - Adenosine receptors mediated intracellular calcium in cumulus cells involved in
      the maintenance of first meiotic arrest.
AB  - Keeping the intact germinal vesicle (GV) is essential for maintaining the
      capacity of mammals including human. It is maintained by very complex procedures
      along with folliculogenesis and is a critical step for getting competent oocyte.
      So far, a few mechanisms involved in folliculogenesis are known but GV arrest
      mechanisms are largely unrevealed. Cyclic AMP, a adenosine derived substance,
      have been used as inhibitor of germinal vesicle breakdown as a putative oocyte
      maturation inhibitor. In this study, we examined the potency of adenosine as GV
      maintainer and a possible signaling mediator for that. A1, A2b, and A3 were
      detected in cumulus cells of cumulus enclosed-oocyte (CEO). Intact of germinal
      vesicle was not kept like in follicle but the spontaneous maturation was
      inhibited by exogenous adenosine. It is inhibited with concentration dependent
      manners. Intracellular calcium level of cumulus was extensively increased after
      adenosine treatment. Based on these results it is suggested that one of the
      pathway for GV arrest by adenosine and its receptors is calcium mediated
      signaling pathway in CEO. 

PMID- 25949132
TI  - Postnatal Development of Subcallosal Zone Following Suppression of Programmed
      Cell Death in Bax-deficient Mice.
AB  - Neural stem cells are found in adult mammalian brain regions including the
      subgranular zone (SGZ) of the dentate gyrus (DG) and the subventricular zone
      (SVZ). In addition to these two regions, other neurogenic regions are often
      reported in many species. Recently, the subcallosal zone (SCZ) has been
      identified as a novel neurogenic region where new neuroblasts are spontaneously
      generated and then, by Bax-dependent apoptosis, eliminated. However, the
      development of SCZ in the postnatal brain is not yet fully explored. The present
      study investigated the precise location and amount of neuroblasts in the
      developing brain. To estimate the importance of programmed cell death (PCD) for
      SCZ histogenesis, SCZ development in the Bax-knockout (KO) mouse was examined.
      Interestingly, an accumulation of extra neurons with synaptic fibers in the SCZ
      of Bax-KO mice was observed. Indeed, Bax-KO mice exhibited enhanced startle
      response to loud acoustic stimuli and reduced anxiety level. Considering the
      prevention of PCD in the SCZ leads to sensory-motor gating dysfunction in the Bax
      KO mice, active elimination of SCZ neuroblasts may promote optimal brain
      function. 

PMID- 25949133
TI  - Morphometric and Histological Changes in Cyprinid Loach, Misgurnus
      anguillicaudatus, in the Early Growth Period.
AB  - In this study, we measured the morphometric and histological changes in the
      cyprinid loach, Misgurnus anguillicaudatus, during the early period of growth.
      Eyes, yolk length, yolk height, and yolk volume of the larva decreased for 16
      days post hatching (DPH) (P<0.05). During 60 DPH (P>0.05), the most anterior
      extension of the head * the posterior end of the supraoccipital, the most
      anterior extension of the head * the origin of the dorsal fin, the most anterior
      extension of the head * the origin of the pectoral fin, the posterior end of the
      supraoccipital * the origin of the pelvic fin, and the origin of the dorsal fin *
      the ventral origin of the caudal fin gradually decreased, whereas the most
      anterior extension of the head * the dorsal origin of the caudal fin, the origin
      of the dorsal fin * the origin of the anal fin, the origin of the dorsal fin *
      the origin of the pectoral fin, and the insertion of the dorsal fin * the origin
      of the pelvic fin gradually increased (P<0.05). In the cyprinid loach, the retina
      is composed of six layers: the epithelial layer, ganglion cell layer, inner
      nuclear layer, inner plexiform layer, outer limiting membrane, and rod and cone
      layer (RCL). After hatching, part of the RCL gradually increased in density. The
      kidney and midgut epithelium were already formed in the cyprinid loach just after
      hatching and grew gradually in subsequent days. 

PMID- 25949134
TI  - Genetic Differences of Three Pollicipes mitella Populations Identified by PCR
      Analysis.
AB  - Genomic DNAs were extracted from the turtle leg (Pollicipes mitella, 1798)
      population of Tongyeong, Yeosu and Manjaedo located in the southern sea of Korea.
      The turtle leg population from Tongyeong (0.929) exhibited higher bandsharing
      values than did turtle leg from Manjaedo (0.852). The higher fragment sizes
      (>1,200 bp) are much more observed in the Yeosu population. The number of unique
      loci to each population and number of shared loci by the three populations,
      generated by PCR using 7 primers in the turtle leg (P. mitella) population of
      Tongyeong, Yeosu and Manjaedo. Genetic distances among different individuals of
      the Tongyeong population of the turtle leg (lane 1-07), Yeosu population of the
      turtle leg (lane 08-14) and Manjaedo population of the turtle leg (lane 15-21),
      respectively, were generated using the CLASSIFICATION option in Systat version 10
      according to the bandsharing values and similarity matrix. The dendrogram,
      obtained by the seven decamer primers, indicated three genetic clusters: cluster
      1 (TONGYEONG 01-TONGYEONG 07), cluster 2 (YEOSU 08-YEOSU 14), and cluster 3
      (MANJEDO 15-MANJEDO 21). Tongyeong population could be evidently discriminated
      with the other two Yeosu and Manjaedo populations among three populations. The
      longest genetic distance (0.305) was found to exist between individuals' no. 02
      of the Tongyeong population and no. 13 of the Yeosu population. It seems to the
      authors that this is a result of a high degree of inbreeding in narrow region for
      a long while. 

PMID- 25949135
TI  - Effect of Pioglitazone on Production of Regulated upon Activation Normal T-cell
      Expressed and Secreted (RANTES) and IVF Outcomes in Infertile Women with
      Endometriosis.
AB  - This study was performed to investigate the effect of peroxisome proliferators
      activated receptor-gamma (PPAR-gamma) ligand, pioglitazone, on production of
      regulated upon activation normal T-cell expressed and secreted (RANTES) and in
      vitro fertilization (IVF) outcome in infertile patients with endometriosis. Sixty
      four infertile patients with stage III or IV endometriosis undergoing IVF were
      randomly allocated to the study or the control group. The long protocol of GnRH
      agonist (GnRH-a) was used for controlled ovarian stimulation (COS) in all
      patients. Patients in the study group were treated with pioglitazone at a dose of
      15 mg/day orally from the starting day of GnRH-a treatment to the day of hCG
      injection. Blood samples were drawn for serologic assay of RANTES on the first
      day of GnRH-a treatment and the day of hCG injection. There were no differences
      between the study and control groups in patient characteristics. There were also
      no differences between the two groups in COS duration, and the numbers of
      retrieved oocytes, fertilized oocytes and embryos transferred. The clinical
      pregnancy rate per cycle was higher in the study group, but this difference was
      not statistically significant. However, embryo implantation rate was
      significantly higher in the study group of 12.5% compared with 8.6% in the
      control group (P<0.05). The serum RANTES levels after pioglitazone treatment were
      significantly lower than those before pioglitazone treatmen in the study group
      (P<0.05). Our data suggest that pioglitazone treatment can suppress RANTES
      production and improve the embryo implantation rate in patients with
      endometriosis undergoing IVF. 

PMID- 25949131
TI  - Potency of melatonin in living beings.
AB  - Living beings are surrounded by various changes exhibiting periodical rhythms in
      environment. The environmental changes are imprinted in organisms in various
      pattern. The phenomena are believed to match the external signal with organisms
      in order to increase their survival rate. The signals are categorized into
      circadian, seasonal, and annual cycles. Among the cycles, the circadian rhythm is
      regarded as the most important factor because its periodicity is in harmony with
      the levels of melatonin secreted from pineal gland. Melatonin is produced by the
      absence of light and its presence displays darkness. Melatonin plays various
      roles in creatures. Therefore, this review is to introduce the diverse potential
      ability of melatonin in manifold aspects in living organism. 

PMID- 25949136
TI  - Fus expression patterns in developing tooth.
AB  - Recently, the RNA/DNA-binding protein FUS, Fused in sarcoma, was shown to play a
      role in growth, differentiation, and morphogenesis in vertebrates. Because little
      is known about Fus, we investigated its expression pattern in murine tooth
      development. In situ hybridization of mouse mandibles at specific developmental
      stages was performed with a DIG-labeled RNA probe. During early tooth
      development, Fus was detected in the dental epithelium and dental mesenchyme at
      11 days postcoitum (dpc) and 12 dpc. From 14 dpc, Fus was strongly expressed in
      the dental papilla and the cervical loop of the dental epithelium. At postnatal
      day 4 (PN4), Fus expression was observed in the odontoblasts, ameloblasts, the
      proliferation zone of the pulp, and the cervical loop. At PN14, the expression
      pattern of Fus was found to be maintained in the odontoblasts and the
      proliferation zone of the pulp. Furthermore, Fus expression was especially strong
      in the Hertwig's epithelial root sheath (HERS). Therefore, this study suggests
      that Fus may play a role in the HERS during root development. 

PMID- 25949137
TI  - Expression Analysis of Cathepsin F during Embryogenesis and Early Developmental
      Stage in Olive Flounder (Paralichthys olivaceus).
AB  - Cathepsins are members of the multigene family of lysosomal cysteine proteinases
      and have regulated function in several life processes. The potential role of
      cathepsin F cysteine gene was expected as protease in the yolk processing
      mechanism during early developmental stage, but expression analysis was unknown
      after fertilization. The alignment analysis showed that amino acid sequence of
      cathepsin F from olive flounder liver expressed sequence tag (EST) homologous to
      cathepsin F of other known cathepsin F sequences with 87-98% identity. In this
      study, we examined the gene expression analysis of cathepsin F in various tissues
      at variety age flounder. Tissue distribution of the cathepsin F mRNA has been
      shown to be ubiquitous and constitutive pattern regardless of age in each group,
      although derived from cDNA library using liver sample. The mRNA level of
      cathepsin F more increased as developmental proceed during embryogenesis and
      early developmental stage, especially increased in the blastula, hatching stage
      and 3 days post hatching (dph). As a result, it may suggest that the proteolysis
      of yolk proteins (YPs) has been implicated as a mechanism for nutrient supply
      during early larval stages in olive flounder. 

PMID- 25949138
TI  - Expression Analysis of Visual Arrestin gene during Ocular Development of Olive
      Flounder (Paralichthys olivaceus).
AB  - Olive flounder (Paralichthys olivaceus) is one of the commercial important
      flatfish species in Korea. The ocular signal transduction pathway is important in
      newly hatched flounders because it is closely involved in the initial feeding
      phase thus essential for survival during the juvenile period. However, the study
      of gene expression during ocular development is incomplete in olive flounder.
      Therefore we examined the expression analysis of specifically induced genes
      during the development of the visual system in newly hatched flounders. We
      searched ocular development-involved gene in the database of expressed sequence
      tags (ESTs) from olive flounder eye and this gene similar to arrestin with a
      partial sequence homology. Microscopic observation of retinal formation
      corresponded with the time of expression of the arrestin gene in the
      developmental stage. These results suggest that arrestin plays a vital role in
      the visual signal transduction pathway of the retina during ocular development.
      The expression of arrestin was strong in the ocular system during the entirety of
      the development stages. Our findings regarding arrestin have important
      implications with respect to its biological role and evolution of G-protein
      coupled receptor (GPCR) signaling in olive flounder. Further studies are required
      on the GPCR-mediated signaling pathway and to decipher the functional role of
      arrestin. 

PMID- 25949139
TI  - Long Photoperiod Affects Gonadal Development in Olive Flounder Paralichthys
      olivaceus.
AB  - To effects of sex maturation in olive flounder by regulating long photoperiod,
      gonadal development and GTH mRNA expression in the pituitary were investigated.
      Photoperiod was treated natural photoperiod and long photoperiod (15L:9D)
      conditions from September 2011 to March 2012. The results showed that natural
      photoperiodic group showed a higher gonadosomatic index (GSI) than long
      photoperiodic group during the spawning season (March 2012). The histological
      analysis of ovarian tissue showed that natural photoperiod group of ovaries
      contained vitellogenic oocytes, but long photoperiod group of ovaries mainly
      contained perinucleolus staged oocyte and oil-drop staged oocytes. The FSH mRNA
      of olive flounder, under natural photoperiod group, showed a significantly higher
      expression but no significant difference under long photoperiod group. The LHbeta
      mRNA showed a significantly higher expression only under natural photoperiod
      group. These results may suggest that long photoperiodic information regulates
      secretion of pituitary FSH and LH and maintain early growing stage of gonadal
      development in this species. 

PMID- 25949140
TI  - Spawning Characteristics and Artificial Hatching of Female Mottled Skate,
      Beringraja pulchra in the West Coast of Korea.
AB  - The gonadsomatic index (GSI) of mottled skate was the highest in April, GSI and
      HSI showed a reverse phase for its reproductive cycle. The fish had one pair of
      egg capsules, having 1 to 7 fertilized eggs, and spawned all the year round. When
      surveying the reproductive characteristics of females over 63 ? in disc width, we
      found the spawning peak was between April to June, and the appearance ratio of
      egg capsules was the highest in May (32.1%). The eggs were hatched at 8 degrees
      C, 13 degrees C, 18 degrees C, water temperature (12.8 to 24.2 degrees C), and
      the best hatching temperature was 18 degrees C. The number of fish hatched was 4
      to 5 fish/egg capsules, and the hatching rate was 100%. The sex ratios of
      hatching larvae were 45.5% female and 54.5% male. Therefore this study will
      provide fundamental data and information for artificial reproduction of the
      mottled skate. 

PMID- 25949141
TI  - Comparative Analysis of the Morphometric Changes in Ussurian bullhead, Leiocassis
      ussuriensis, and Korean bullhead, Pseudobagrus fulvidraco, in the Early Period of
      Growth.
AB  - Morphometric changes in the Ussurian bullhead, Leiocassis ussuriensis, and the
      Korean bullhead, Pseudobagrus fulvidraco, were observed during the early period
      of growth. Yolk length, yolk height, and yolk volume in the two species decreased
      within 9 days post-hatching (DPH) (p<0.05). The body lengths and body heights of
      both species increased gradually to 150 and 130 DPH, respectively (p<0.05). The
      horizontal distance between the anteriormost extension of the head and the
      anterior insertion of the pectoral fin, the anteriormost extension of the head *
      the verticality position of the anterior insertion of the primary dorsal fin
      rays, and the anterior insertion of the primary dorsal fin * the anterior
      insertion of the pectoral fin were greater in the Korean bullhead than in the
      Ussurian bullhead (p<0.05). However, the relative sizes of the head region,
      pectoral fin, ventral fin, and anal fin were greater in the Ussurian bullhead
      than in the Korean bullhead (p<0.05), and relative body depth and the size of the
      outer-mandible barbel were greater in the Korean bullhead than in the Ussurian
      bullhead (p<0.05). The growth curves of the morphometric characteristics of both
      species were divided into three types. 

PMID- 25949142
TI  - The Effect of Fibroblast Co-culture on In Vitro Maturation of Mouse Preantral
      Follicles.
AB  - This study was performed to evaluate the effects of fibroblast co-culture on in
      vitro maturation (IVM) of prepubertal mouse preantral follicles. The intact
      preantral follicles were obtained from the ovaries of 12-14 day old mice and
      these were cultured individually in alpha-minimal essential medium (alpha-MEM)
      supplemented with 5% fetal bovine serum (FBS), 100 mIU/Ml recombinant follicle
      stimulating hormone (rFSH), 1% insulin-transferrin-selenium, 100 MUg/ml
      penicillin and 50 MUg/Ml streptomycin as base medium for 12 days. A total of 200
      follicles were cultured in base medium co-cultured with mouse embryonic
      fibroblast (MEF) (MEF group) (n=100) or only base medium as control group
      (n=100). Survival rate of follicles on day 12 of culture were significantly
      higher in the MEF group of 90.0%, compared with 77.0% of the control group
      (p=0.021). Follicle diameters on day 6 and 8 of the culture period were
      significantly larger in the MEF group than those in the control group (p=0.021,
      p=0.007, respectively). Estradiol levels in culture media on day 4, 6, 8, 10 and
      12 of the culture period were significantly higher in the MEF group (p=0.043,
      p=0.021, p=0.006, p<0.001 and p=0.008, retrospectively). Our data suggest that
      MEF cell co-culture on IVM of mouse preantral follicle increases survival rate
      and promotes follicular growth and steroid production. 

PMID- 25949143
TI  - Diphlorethohydroxycarmalol of Ishige okamurae and Caffeine Modified the
      Expression of Extracellular Fibrillars during Adipogenesis of Mouse Subcutaneous
      Adipose Derived Stem Cell.
AB  - Although, one of the etiologies of localized lipodystrophy of the subcutaneous
      connective tissue (cellulite) is the histological alternation of adipose tissue,
      the characteristics of expression of the components of extracellular matrix (ECM)
      components during adipogenesis are not uncovered. In this study, the effects of
      caffeine and Ishige okamurae originated diphlorethohydroxycarmalol (DPHC) on the
      expression of extracellualr fibers was analyzed with quantitative RT-PCR during
      differentiation induction of mouse subcutaneous adipose derived stem cells
      (msADSC) into adipocyte. The expression levels of Col1a, Col3a1, and Col61a were
      decreased by the adipogenci induction in a time-dependent manners. However, Col2a
      mRNA and Col4a1 mRNA expressions were oposit to them. Caffeine and DPHC
      stimulated the changes of the expression of these collagens. Eln mRNA expression
      was increased by induction. DPHC stimulated the expression of it. Mfap5 mRNA
      expression was deceased in both adipogenic cell and matured adipocytes. Caffeine
      suppressed the expression of Mfap5 but the effect of DPHC was different by the
      concentration. The expression of bioglycan, decorin, and lumican were also
      modified by caffeine and DPHC in a concentration-dependent manner. Based on this
      study, we revealed firstly the effects of caffeine and DPHC on the expression of
      collagens, elastin, and glycoproteins during adipogenesis of msADSCs. Those
      results suggest that DPHC may have antiadipogenic effect and has more positive
      effets on normal adipose tissue generation and work as suppressor the abnormality
      of ECM structure. Such results indicate that DPHC can be applied in keeping the
      stability of the ECM of adipogenic tissues. 

PMID- 25949144
TI  - Expressional Changes of Water Transport-related Molecules in the Efferent
      Ductules and Initial Segment of Mouse Treated with Bisphenol A-Containing
      Drinking Water for Two Generations.
AB  - Bisphenol A (BPA) is an estrogenic endocrine disrupter. However, depending on a
      way of treatment, the harmful effects of BPA have not been confirmed. Also, trans
      generational effects of BPA on male reproduction are still controversial. Because
      the reabsorption of testicular fluid in the efferent ductules (ED) and initial
      segment (IS) is important for sperm maturation, the present study was designed to
      determine trans-generational effect of BPA administrated orally on expression of
      water transport-related molecules in the mouse ED and IS. Ethanol-dissolved BPA
      was diluted in water to be 100 ng (low), 10 MUg (medium), and 1 mg/Ml water
      (high). BPA-containing water was provided for two generations. Expression of ion
      transporters and water channels in the ED and IS were measured by relative real
      time PCR analysis. In the ED, BPA treatment caused expressional increases of
      carbonic anhydrase II, cystic fibrosis transmembrane regulator, Na(+)/K(+) ATPase
      alpha1 subunit, and aquaporin (AQP) 1. No change of Na(+)/H(+) exchange (NHE) 3
      expression was detected. BPA treatment at medium dose resulted in an increase of
      AQP9 expression. In the IS, the highest expressional levels of all molecules
      tested were observed in medium-dose BPA treatment. Generally, high-dose BPA
      treatment resulted in a decrease or no change of gene expression. Fluctuation of
      NHE3 gene expression by BPA treatment at different concentrations was detected.
      These findings suggest that trans-generational exposure to BPA, even at low dose,
      could affect gene expression of water-transport related molecules. However, such
      effects of BPA would be differentially occurred in the ED and IS. 

PMID- 25949145
TI  - PKCeta Regulates the TGFbeta3-induced Chondevrepogenic Differentiation of Human
      Mesenchymal Stem Cell.
AB  - Transforming growth factor (TGF) family is well known to induce the
      chondevrepogenic differentiation of mesenchymal stem cells (MSC). However, the
      precise signal transduction pathways and underlying factors are not well known.
      Thus the present study aims to evaluate the possible role of C2 domain in the
      chondevrepogenic differentiation of human mesenchymal stem cells. To this end,
      145 C2 domains in the adenovirus were individually transfected to hMSC, and
      morphological changes were examined. Among 145 C2 domains, C2 domain of protein
      kinase C eta (PKCeta) was selected as a possible chondevrepogenic differentiation
      factor for hMSC. To confirm this possibility, we treated TGFbeta3, a well known
      chondevrepogenic differentiation factor of hMSC, and examined the increased
      expression of glycosaminoglycan (GAG), collagen type II (COL II) as well as
      PKCeta using PT-PCR, immunocytochemistry and Western blot analysis. To further
      evaluation of C2 domain of PKCeta, we examined morphological changes, expressions
      of GAG and COL II after transfection of PKCeta -C2 domain in hMSC. Overexpression
      of PKCeta-C2 domain induced morphological change and increased GAG and COL II
      expressions. The present results demonstrate that PKCeta involves in the TGF
      beta3-induced chondevrepogenic differentiation of hMSC, and C2 domain of PKCeta
      has important role in this process. 

PMID- 25949146
TI  - The Expression Analysis of Complement Component C3 during Early Developmental
      Stages in Olive Flounder (Paralichthys olivaceus).
AB  - Fish larvae are immediately exposed to microbes from hatching to maturation of
      their lymphoid organs, therefore effective innate mechanisms is very important
      for survival in such an environment. The key component of innate immune system,
      C3 is central protein of all activation pathways of the complement system,
      leading to inflammatory reactions, such as opsonisation, chemotaxis, and cell
      lysis of pathogens. Although, innate mechanisms is essential for survival in the
      early stage of development, little is known about defence mechanisms. In this
      study, the alignment analysis showed that amino acid sequence of C3 from olive
      flounder liver EST homologous to other known C3 sequences with 73-99% identity.
      Also, we examined the tissue distribution of olive flounder C3 and analyzed
      expression pattern from the fertilized egg until 28 days post hatching. As a
      result, olive flounder C3 mRNA was expressed only in the liver and the mRNA level
      more increased as developmental proceed during the early stage. These results may
      suggest that olive flounder C3 plays an important function in the early immune
      response of olive flounder larvae. 

PMID- 25949147
TI  - Expression of Perforin Gene for Early Development of Nephrons in Olive Flounder
      (Paralichthys olivaceus).
AB  - The innate immune system is the only defense weapon that invertebrates have, and
      it is the fundamental defense mechanism for fish. The innate immune response is
      important in newly hatched flounders because it is closely involved in the
      initial feeding phase, which is why it is essential for survival during the
      juvenile period. The expression analysis of genes involved in the innate immune
      response in the olive flounder (Paralichthys olivaceus) in the days after
      hatching is incomplete. Therefore, we have begun to examine the expression
      patterns of genes specifically induced during the development of the innate
      immune system in newly hatched flounders. Microscopic observation showed that
      pronephron formation corresponded with the expression of perforin-encoding gene.
      These results suggest that perforin plays a vital role in the innate immunity of
      the kidney during developmental stages. Perforin expression was strong at the
      start of the development of the innate immune response, and continued throughout
      all the development stages. Our findings have important implications with respect
      to perforin's biological role and the evolution of the first defense mechanisms
      in olive flounder. Further studies are required to elucidate the perforin
      mediated innate immunity response and to decipher the functional role of perforin
      in developmental stages. 

PMID- 25949148
TI  - Stage and Tissue Specific Expression of Four TCR Subunits in Olive Flounder
      (Paralichthys olivaceus).
AB  - TCR subunits are members of membrane-bound receptors which allow the fast and
      efficient elimination of the specific fish pathogens have regulated function in
      adaptive immunity. Sequence structure of TCR subunits have been reported for
      various teleosts, but the information of each TCR subunit functional
      characterization through expression analysis in fish was unknown. In this study,
      we examined the gene expression of TCR subunits in the early developmental stages
      and observed transcript levels in various tissues from healthy adult olive
      flounder by RT-PCR. The mRNA expression of alpha subunit was already detected in
      the previous hatching step. But the transcripts of another TCR subunit were not
      observed during embryo development and increased after hatching and maintained
      until metamorphosis at the same level. It was found that all TCR subunits mRNAs
      are commonly expressed in the immune-related organ such as spleen, kidney and
      gill, also weak expressed in fin and eye. TCR alpha and beta subunit were
      expressed in brain, whereas gamma and delta were not expressed same tissue. The
      sequence alignment analysis shows that there are more than 80% sequence homology
      between TCR subunits. Because it has a high similarity of amino acid sequence to
      expect similar in function, but expression analysis show that will have may
      functional diversity due to different time and place of expression. 

PMID- 25949149
TI  - Survival Rates with Time Course of Frozen-thawed Pacific Oyster Larvae in Indoor
      Rearing System.
AB  - Post-thawed larval rearing in Pacific oyster Crassostrea gigas was performed to
      investigate the survival rate with time course in three kinds of larvae
      cryopreserved. The highest survival rate and larval activity index (LAI) of post
      thawed larvae were obtained from the permeation in 0.2 M sucrose and 2.0 M
      ethylene glycol (EG) at -1 degrees C/min in freezing speed showing the survival
      rates just after thawing of 63.8% in trochophore, 84.1% in D-shaped veliger and
      56.3% in early umbo veliger. In post-thawed larval rearing with food supply, the
      larvae lasted their lives until 24 hours in trochophore, 75 hours in D-shaped
      veliger and 57 hours in early umbo veliger. The results suggested that each
      larval stage post-thawed revealed no more further development to subsequent
      respective stage. 

PMID- 25949150
TI  - Evaluation of Fertilizing Ability using Frozen Thawed Sperm in the Longtooth
      Grouper, Epinephelus bruneus.
AB  - This study examines the effects on fertilization rate (FR), hatching rate (HR),
      and normal individual rate after artificial fertilization using frozen thawed
      sperm according to the cryoprotectant (DMSO) concentration and the period of
      cryopreserved sperm of longtooth grouper, Epinephelus bruneus. Performing
      artificial fertilization using frozen-thawed sperm, after freezing the sperm at
      different DMSO concentration of 5.0%, 7.5%, 10.0% respectively, FR were (DMSO
      5.0%: 99.5+/-0.8%, DMSO 7.5%: 99.5+/-0.7%, and DMSO 10.0%: 99.6+/-0.6%). The
      results are not significantly different from the control fresh sperm (100%). HR
      also (DMSO 5.0%: 96.2+/-2.3%, DMSO 7.5%: 95.3+/-3.6%, 10.0%: 96.6+/-1.8%) were
      not significantly different in each group. The normal individual rate after
      hatching using with control fresh sperm (98.4%+/-0.5) and DMSO concentration
      level of 5.0% (97.8+/-0.1%) were not significantly different. However, with 7.5%
      (97.2+/-0.6%) and 10.0% DMSO concentrations (95.9+/-0.2%) are lower than the
      normal individual rate after hatching observed in the control and 5.0% DMSO.
      Performing artificial fertilization using frozen-thawed sperm at different frozen
      period (2 days, 2 years, and 3 years), 10% DMSO FR and HR of 3 years (FR; 66.8+/
      1.8%, HR: 82.0+/-12.9%) and 2 years (FR; 78.5+/-14.8%, HR: 79.3+/-0.6%)
      cryopreserved sperm were lower than control (FR; 100%, HR: 91.1+/-3.6%) and 2
      days cryopreserved sperm (FR; 99.6+/-0.6%, HR: 96.6+/-1.8%). These results
      suggest suitable DMSO concentration ranges of cryopreservation sperm for E.
      bruneus is 5 to 10% and with 2 to 3 years cryopreservation period,
      cryopreservation sperm can be useful for seed production. 

PMID- 25949151
TI  - Reproductive Cycle of Chameleon Goby, Tridentiger trigonocephalus in the Southern
      Coastal Waters of Korea.
AB  - The objective of this study was to characterize the reproductive cycle of the
      chameleon goby, T. trigonocephalus. Gonadal development was investigated using a
      histological method. Specimens were collected monthly, from April 2009 to March
      2010. The gonadosomatic index (GSI) of females began to increase in April,
      reaching the maximum in May, and declined sharply in August. In males, the GSI
      began to increase in April and reaching the maximum in July. The annual
      reproductive cycle of T. trigonocephalus can be divided into four successive
      stages in females: the growing (November-March), maturing (April-May), ripe and
      spawning (June-July), and recovery (August-October) stages. Males passed through
      growing (November-March), maturing (April-June), ripe and spermiation (July
      August), and recovery (September-October) stages. These results indicate the
      spawning season is from June to July. The relationship between fecundity (Fc) and
      body length (BL) was Fc=86.1511BL(2.6506). Fecundity was ranged from 3,448-9,654
      eggs in a BL of 4.8-7.2 cm and it was increased as BL increased. 

PMID- 25949152
TI  - Genetic Variations between Hairtail (Trichiurus lepturus) Populations from Korea
      and China.
AB  - PCR analysis generated on the genetic data showed that the geographic hairtail
      (Trichiurus lepturus) population from Korea in the Yellow Sea was more or less
      separated from geographic hairtail population from China in the South Sea. The
      average bandsharing value (mean+/-SD) within hairtail population from Korea
      showed 0.859+/-0.031, whereas 0.752+/-0.039 within population from China. Also,
      bandsharing values between two hairtail populations ranged from 0.470 to 0.611,
      with an average of 0.542+/-0.059. As compared separately, the bandsharing values
      of individuals within hairtail population from Korea were comparatively higher
      than those of individuals within population from China. The hierarchical
      dendevrepogram resulted from reliable oligonucleotides primers, indicating two
      genetic clusters composed of cluster 1 (KOREANHAIR1~KOREANHAIR11) and cluster 2
      (CHINESEHAI12~CHINESEHAI22). The genetic distances between two geographic
      populations ranged from 0.038 to 0.476. Individual No. 11 within hairtail
      population from Korea was genetically closely related with No. 10 (genetic
      distance=0.038). The longest genetic distance (0.476) displaying significant
      molecular difference was also between individual No. 01 within hairtail
      population from Korea and No. 22 from Chinese. In the present study, PCR analysis
      has revealed significant genetic distances between two hairtail population pairs
      (P<0.05). 

PMID- 25949153
TI  - Effect of Water Temperature and Salinity on the Fertilized Egg Development and
      Larval Development of Sevenband Grouper, Epinephelus septemfasciatus.
AB  - The fertilized eggs of E. septemfasciatus are spherical and transparent with
      buoyancy at 790 to 890 MUm (average 821.8+/-2.0 MUm) in diameter with 170 to 230
      MUm oil globules (average 192.9+/-0.93 MUm). Hatching began approximately 46 and
      35 hours after fertilization at 22.0 degrees C and 25.0 degrees C water
      temperature, respectively. The average total length of newly hatched larvae was
      1.75+/-0.03 mm. Most of the yolk and oil globules were absorbed within 3 to 4
      days after hatching. The larvae reached 2.48 to 2.72 mm in total length, and
      their mouths and anuses opened at 3 to 4 days after hatching. In this time, the
      mouth diameters of the larvae were 0.209 to 0.238 mm. The larvae reached 3.24 to
      4.15 mm in total length at 11 to 17 days after hatching, and began to
      metamorphose at the time the second dorsal and pelvic spines appeared and
      elongated. The abdominal cavity was densely lined with melanophores. The larvae
      reached 5.12 mm in total length at 24 days after hatching. 

PMID- 25949154
TI  - Enhancement of Transgene Expression by HDAC Inhibitors in Mouse Embryonic Stem
      Cells.
AB  - Embryonic stem (ES) cells can self-renew and differentiate to various cells
      depending on the culture condition. Although ES cells are a good model for cell
      type specification and can be useful for application in clinics in the future,
      studies on ES cells have many experimental restraints including low transfection
      efficiency and transgene expression. Here, we observed that transgene expression
      after transfection was enhanced by treatment with histone deacetylse (HDAC)
      inhibitors such as trichostatin A, sodium butyrate, and valproic acid.
      Transfection was performed using conventional transfection reagents with a
      retroviral vector encoding GFP under the control of CMV promoter as a reporter.
      Treatment of ES cells with HDAC inhibitors after transfection increased
      population of GFP positive cells up to 180% compared with untreated control. ES
      cells showed normal expression of stem cell markers after treatment with HDAC
      inhibitors. Transgene expression was further enhanced by modifying transfection
      procedure. GFP positive cells selected after transfection were proved to have the
      stem cell properties. Our improved protocol for enhanced gene delivery and
      expression in mouse ES cells without hampering ES cell properties will be useful
      for study and application of ES cells. 

PMID- 25949155
TI  - Expression of Hr-Erf Gene during Ascidian Embryogenesis.
AB  - FGF9/16/20 signaling pathway specify the developmental fates of notochord,
      mesenchyme, and neural cells in ascidian embryos. Although a conserved
      Ras/MEK/Erk/Ets pathway is known to be involved in this signaling, the detailed
      mechanisms of regulation of FGF signaling pathway have remained largely elusive.
      In this study, we have isolated Hr-Erf, an ascidian orthologue of vertebrate Erf,
      to elucidate interactions of transcription factors involved in FGF signaling of
      the ascidian embryo. The Hr-Erf cDNA encompassed 3110 nucleotides including
      sequence encoded a predicted polypeptide of 760 amino acids. The polypeptide had
      the Ets DNA-binding domain in its N-terminal region. In adult animals, Hr-Erf
      mRNA was predominantly detected in muscle, and at lower levels in ganglion,
      gills, gonad, hepatopancreas, and stomach by quantitative real-time PCR (QPCR)
      method. During embryogenesis, Hr-Erf mRNA was detected from eggs to early
      developmental stage embryos, whereas the transcript levels were decreased after
      neurula stage. Similar to the QPCR results, maternal transcripts of Hr-Erf was
      detected in the fertilized eggs by whole-mount in situ hybridization. Maternal
      mRNA of Hr-Erf was gradually lost from the neurula stage. Zygotic expression of
      Hr-Erf started in most blastomeres at the 8-cell stage. At gastrula stage, Hr-Erf
      was specifically expressed in the precursor cells of brain and mesenchyme. When
      MEK inhibitor was treated, embryos resulted in loss of Hr-Erf expression in
      mesenchyme cells, and in excess of Hr-Erf in a-line neural cells. These results
      suggest that zygotic Hr-Erf products are involved in specification of mesenchyme
      and neural cells. 

PMID- 25949156
TI  - Induced Morphological Changes in Larval Rock Bream, Oplegnathus fasciatus, under
      Starvation.
AB  - Morphological changes in the reared rock bream, Oplegnathus fasciatus, from
      hatching to six days after hatching were examined during the early growth stage
      under starvation. All the larvae died within five days when feeding was delayed
      for three days after hatching. These results imply that initial larval food
      should be supplied within two days of hatching. Changes in the pectoral angle and
      the ratios of eye height to head height, gut height to standard length, and gut
      height to myotome height in the rock bream are alternative indicators for the
      identification of starving fish. These indicators might prove useful in
      evaluating the successful transition from endogenous to exogenous feeding in this
      species. 

PMID- 25949158
TI  - In Vitro Steroidogenesis on Oocyte Development in the Starry Flounder,
      Platichthys stellatus.
AB  - In this study, oocyte steroidogenesis are investigated in relation to oocyte
      development in the starry flounder, Platichthys stellatus, a marine multiple
      spawner. Vitellogenic (0.52 and 0.55 mm oocyte diameter) and mature oocytes
      (0.63, 0.66 and 0.71 mm oocyte diameter) were incubated in vitro in the presence
      of [(3)H]17alpha-hydevrepoxyprogesterone ([(3)H]17alpha-OHP) as a precursor.
      Steroid metabolites were extracted from the incubated media and oocytes, the
      extracts were separated and identified by thin-layer chromatography (TLC), high
      performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry
      (GC-MS). The major metabolites produced from [(3)H]17alpha-OHP were andevrepogens
      [andevrepostenedione (A4) and testosterone (T)] and estrogens [17beta-estradiol
      (E2) and estrone (E1)] and progestins [17alpha,20alpha-dihydevrepoxy-4-pregnen-3
      one (17alpha20alphaP) and 17alpha,20beta-dihydevrepoxy-4-pregnen-3-one
      (17alpha20betaP)] in vitellogenic and mature oocytes. The results from this study
      suggest the potential roles of E1 in the oocytes with diameter 0.52-0.71 mm,
      17alpha20alphaP and 17alpha20betaP at the oocytes of 0.63, 0.66 and 0.71 mm. 

PMID- 25949157
TI  - A role of cell adhesion molecules and gelatinases in human serum-induced
      aggregation of human eyelid-derived stem cells in vitro.
AB  - Human serum (HS) has been reported to induce aggregation of human eyelid adipose
      derived stem cells (HEACs) during high-density culture in vitro. The present
      study focused on the role of cell adhesion molecules and gelatinases during HS
      induced aggregation of HEACs. HS-induced aggregation occurred between 9-15 days
      of culture. Cells aggregated by HS medium (HS-agg) showed stronger expression of
      alpha2, alpha2B, alphaX, and CEACAM1 genes compared to non-aggregated cells in HS
      medium (HS-ex) or in control FBS-cultured cells. HS-agg were distinctly labeled
      with antibodies against alpha2, alpha2B, and alphaX proteins. Western blot
      results demonstrated that the two integrin proteins were greatly expressed in HS
      agg compared to HS-ex and control FBS-cultured cells. Treatment of HEACs with
      anti-integrin alpha2 antibody during culture in HS medium delayed aggregation
      formation. HS-agg exhibited strong expression of MMP1 and MMP9 compared to HS-ex
      or FBS-cultured cells. Conditioned media from HS-culture showed remarkable
      increase of MMP9 gelatinolytic activity in comparison to those from FBS-culture.
      However, there was no change of TIMP mRNA expression in relation to the HS
      induced aggregation. Based on these results, it is suggested that integrin
      alpha2, alpha2B, and alphaX, and MMP9 might play an important role in the HS
      induced aggregation of HEACs. 

PMID- 25949159
TI  - Comparative Analysis of Histological Changes in Ussurian Bullhead, Leiocassis
      ussuriensis, and Korean Bullhead, Pseudobagrus fulvidevrepaco, in the Early
      Period of Growth.
AB  - The histological changes in the Ussurian bullhead, Leiocassis ussuriensis, and
      the Korean bullhead, Pseudobagrus fulvidevrepaco, were observed during the early
      period of growth. The retinas size of both species increased in the 9 days post
      hatching (DPH) (p<0.05). In the just-hatched Ussurian bullhead, the retina
      already consisted of six layers: the epithelial layer, ganglion cell layer, inner
      nuclear layer, inner plexiform layer, outer limiting membrane layer, and rod and
      cone layer. The Korean bullhead had the same components. At 50 DPH, the thickness
      of the retina was 538.0+/-7.19 MUm in the Ussurian bullhead and 558.9+/-9.44 MUm
      in the Korean bullhead. The relative thickness of each layer of the retina did
      not differ significantly in the two species. Although the growth of the Korean
      bullhead's retina was faster, the relative thickness of each layer in the retina
      did not change during early development. After hatching, some parts of the tissue
      gradually became denser. Immediately after hatching, the kidney and midgut
      epithelium of the Ussurian bullhead and Korean bullhead were already formed and
      grew gradually thereafter. From 0 DPH to 30 DPH, the nuclear height in the midgut
      epithelium did not differ significantly between the two species, but at 50 DPH,
      it was 11.4+/-2.45 MUm in the Korean bullhead and 9.9+/- 2.13 MUm in the Ussurian
      bullhead. During the experimental period, the major axes, minor axes, surface
      areas, and volumes of the proximal tubule cells in the kidney did not differ
      significantly between the two species. Thus, the early histological development
      of the Ussurian bullhead is similar to that of the Korean bullhead. 

PMID- 25949160
TI  - Intratesticular injection of hypertonic saline : non-invasive alternative method
      for animal castration model.
AB  - Previous studies, including our own, have demonstrated that the intratesticular
      injection of hypertonic saline (20%) decreased serum testosterone level which was
      similar to the surgical castration in the rat, showing the state of chemical
      castration. In the present study, we further verify the efficacy of this less
      invasive method as an alternative of surgical orchidectomy in the
      andevrepological field. Sterilized 20% saline was directly injected into the
      adult male rats (750 MUl per testis). The tested rats were divided into 3 groups
      including intact group (intact), orchidectomy group (ORX) and saline injection
      group (SAL) after bilateral orchidectomy was performed at the same day of
      injection. All rats were sacrificed at 4 weeks after injection. The reproductive
      organs (testes, epididymis, seminal vesicles and prostates) were collected and
      used for DNA and protein pattern analyses. Also, patho-histological studies on
      the testes were performed. In contrast to the intact group, similar DNA damages
      of testis and seminal vesicle were appeared in ORX group and SAL group. The DNA
      degradations seemed to be the results of necrosis rather than apoptosis. In the
      protein pattern analysis, all the testing tissues exerted similar patterns in the
      ORX group and the SAL group compared to the those of intact group. Patho
      histological studies revealed that severe degenerative changes in testicular
      seminiferous tubules and massive infiltration of immune cells in SAL group. The
      present study confirmed that direct injection of hypertonic saline into the
      testis caused the equivalent biochemical changes in the accessory sex organs as
      shown in the orchidectomized animals. These results suggest that hypertonic
      saline injection model could be a useful castration model which can substitute
      for surgical castration when its safety is secured through further study in the
      future. 

PMID- 25949161
TI  - Thymocyte Differentiation is Regulated by a Change in Estradiol Levels during the
      Estrous Cycle in Mouse.
AB  - Recent study showed that T cells in the immune organs and peripheral blood are
      influenced by estradiol, leading to a dysfunction of the immune system. However,
      little is known about the thymic-gonadal relationship during the estrous cycle in
      mouse. Therefore, the purpose of this study was to elucidate the mechanism by
      which a change in estradiol levels during the estrous cycle regulates the
      development of T cells in the mouse thymus. Six-week-old ICR mice were used and
      divided into four groups, including diestrous, proestrous, estrous, and
      metestrous. We first confirmed that ER-alpha and - beta estrogen receptors were
      expressed in thymic epithelial cells, showing that their expression was not
      different during the estrous cycle. There was also no significant difference in
      thymic weight and total number of thymocytes during the estrous cycle. To
      determine the degree of thymocyte differentiation during the estrous cycle, we
      analyzed thymocytes by flow cytometry. As a result, the percentage of CD4+CD8+
      double-positive (DP) T cells was significantly decreased in the proestrous phase
      compared to the diestrous phase. However, CD4+CD8- or CD4-CD8+ (SP) T cells were
      significantly increased in the proestrous phase compared to the diestrous phase.
      In addition, the percentage of CD44+CD25- (DN1) T cells was significantly
      decreased in the estrous phase compared to other phases, whereas the percentages
      of CD44+CD25+ (DN2), CD44-CD25+ (DN3), and CD44-CD25- (DN4) were not changed
      during the estrous cycle. These results indicate that the development of
      thymocytes may arrest in the DP to SP transition stage in the proestrous phase
      displaying the highest serum level of estradiol. This study suggests that a
      change in estradiol levels during the estrous cycle may be involved in the
      regulation of thymocyte differentiation in the mouse thymus. 

PMID- 25949162
TI  - Suppressive Effects of an Ishige okamurae extract on 3T3-L1 Preadipocyte
      Differentiation.
AB  - The biological activity of tissue specific stem cell is under the control of
      their specific microenvironment and the exogenous chemicals derived from
      digestive tract can be one of the constructing factors of that. It is suggested
      that the extract of brown algae Ishige okamurae has antioxidant-, apoptosis
      induction-, and antiinflammatory- effects. On the other hand, a few studies have
      shown that antioxidant assist inhibition of accumulation of fat. So we studied
      the effect of the extract of I. okamura on the cellular activity and
      differentiation of 3T3-L1 preadipocyte to adipose cell. The viability of cell was
      analyzed using 3-[4,5-dimethylthiazo-2-yl]-2,5-diphenyl tetrazolium bromide (MTT)
      assay. Adipogenesis of 3T3-L1 cell was analyzed after induction in the induction
      medium containing the I. okamurae extract. The cellular activity was high
      compared with the vehicle and 0.05 mM caffeine in all groups of I. okamurae
      extract treated cells. The extract of I. okamura inhibited accumulation of lipids
      in 10 and 50 MUg/ml. The expression of the marker genes for adipocyte
      differentiation coincided with cytochemical results. These results suggest that
      the extract of I. okamurae increases the cellular viability of adipose precursor
      cells. On the other hand, it suppresses the differentiation of preadipocyte to
      adipocyte and accumulation of lipids in concentration-dependent manners. It may
      be possible that the major component of the extract can be applied in the control
      of adipose tissuegenesis. 

PMID- 25949164
TI  - Differential Growth of the Reproductive Organs during the Peripubertal Period in
      Male Rats.
AB  - In mammals, puberty is a process of acquiring reproductive competence, triggering
      by activation of hypothalamic kisspeptin (KiSS)-gonadotropin releasing hormone
      (GnRH) neuronal circuit. During peripubertal period, not only the external
      genitalia but the internal reproductive organs have to be matured in response to
      the hormonal signals from hypothalamic-pituitary-gonadal (H-P-G) axis. In the
      present study, we evaluated the maturation of male rat accessory sex organs
      during the peripubertal period using tissue weight measurement, histological
      analysis and RT-PCR assay. Male rats were sacrificed at 25, 30, 35, 40, 45, 50,
      and 70 postnatal days (PND). The rat accessory sex organs exhibited differential
      growth patterns compared to those of non-reproductive organs. The growth rate of
      the accessory sex organs were much higher than the those of non-reproductive
      organs. Also, the growth spurts occurred differentially even among the accessory
      sex organs; the order of prepubertal organ growth spurts is testis = epididymis >
      seminal vesicle = prostate. Histological study revealed that the presence of
      sperms in seminiferous tubules and epididymal ducts at day 50, indicating the
      puberty onset. The number of duct and the volume of duct in epididymis and
      prostate were inversely correlated during the experimental period. Our RT-PCR
      revealed that the levels of hypothalamic GnRH transcript were increased
      significantly on PND 40, suggesting the activation of hypothalamic GnRH pulse
      generator before puberty onset. Studies on the peripubertal male accessory sex
      organs will provide useful references on the growth regulation mechanism which is
      differentially regulated during the period in andevrepogen-sensitive organs. The
      detailed references will render easier development of endocrine disruption assay.

PMID- 25949163
TI  - Expression of Nesfatin-1/NUCB2 in Fetal, Neonatal and Adult Mice.
AB  - Nesfatin-1/NUCB2, which is associated with the control of appetite and energy
      metabolism, was reported for the first time to be expressed in the hypothalamus.
      However, recent studies have shown that nesfatin-1/NUCB2 was expressed not only
      in the hypothalamus, but also in various tissues including digestive and
      reproductive organs. We also demonstrated that nesfatin-1/NUCB2 was expressed in
      the reproductive organs, pituitary gland, heart, lung, and gastrointestinal tract
      of the adult mouse. However, little is known about nesfatin-1/NUCB2 expression in
      fetal and neonatal mice. Therefore, we examined here the distribution of nesfatin
      1/NUCB2 in various organs of fetal and neonatal mice and compared them with the
      distribution in adult mice. As a result of immunohistochemical staining, nesfatin
      1/NUCB2 protein was expressed relatively higher in the lung, kidney, heart, and
      liver compared to other organs in the fetus. Western blot results also showed
      that nesfatin-1/NUCB2 protein was detected in the lung, kidney, heart, and
      stomach. Next, we compared the expression levels of nesfatin-1/NUCB2 mRNA in the
      fetus and neonate with the expression levels in both male and female adult mice.
      The expression levels in heart, lung, stomach, and kidney were higher compared
      with other organs in fetal and neonatal mice and in both male and female adult
      mice. Interestingly, the expression of nesfatin-1/NUCB2 mRNA in the kidney was
      devrepamatically increased in male and female adult mice compared to fetal and
      neonatal mice. These results indicate that nesfatin-1/NUCB2 may regulate the
      development and physiological function of mouse organs. In the future, we need
      more study on the function of nesfatin-1/NUCB2, which is highly expressed in the
      heart, lung, and kidney during mouse development. 

PMID- 25949165
TI  - Conflict of interersts in scientific study and bioethics as professionalism.
AB  - Science in the 21st century does not consider participants' welfare, safety and
      human rights in clinical studies, but modern science puts economic profits in its
      priority. This leads to a growing concern about social responsibility and
      professionalism ethics of companies, sponsors and scientists. Specifically, there
      is no way to control conflicts of participants' welfare with economic profits,
      leading to simply relying on individual ethics, social responsibilities and
      audit. This paper helps relevant agencies and people involved understand conflict
      of interest. Also this study presents the guidelines as well as independence,
      autonomy, ethical imagination and phronesis required for scientists. 

PMID- 25949166
TI  - Identification of egr1 direct target genes in the uterus by in silico analyses
      with expression profiles from mRNA microarray data.
AB  - Early growth response 1 (Egr1) is a zinc-finger transcription factor to direct
      second-wave gene expression leading to cell growth, differentiation and/or
      apoptosis. While it is well-known that Egr1 controls transcription of an array of
      targets in various cell types, downstream target gene(s) whose transcription is
      regulated by Egr1 in the uterus has not been identified yet. Thus, we have tried
      to identify a list of potential target genes of Egr1 in the uterus by performing
      multi-step in silico promoter analyses. Analyses of mRNA microarray data provided
      a cohort of genes (102 genes) which were differentially expressed (DEGs) in the
      uterus between Egr1(+/+) and Egr1(-/-) mice. In mice, the frequency of putative
      EGR1 binding sites (EBS) in the promoter of DEGs is significantly higher than
      that of randomly selected non-DEGs, although it is not correlated with expression
      levels of DEGs. Furthermore, EBS are considerably enriched within -500 bp of
      DEG's promoters. Comparative analyses for EBS of DEGs with the promoters of other
      species provided power to distinguish DEGs with higher probability as EGR1 direct
      target genes. Eleven EBS in the promoters of 9 genes among analyzed DEGs are
      conserved between various species including human. In conclusion, this study
      provides evidence that analyses of mRNA expression profiles followed by two-step
      in silico analyses could provide a list of putative Egr1 direct target genes in
      the uterus where any known direct target genes are yet reported for further
      functional studies. 

PMID- 25949167
TI  - Early Life History of the Sevenband Grouper, Epinephelus septemfasciatus from
      Korea.
AB  - This study is conducted to monitor the morphological developmental features of
      the egg development, larvae and juvenile of Epinephelus septemfasciatus, the
      fertilized eggs were gotton using artificial insemination. Matured parents are
      collected from marine caged fish farms in Geomun-ri, Samsan-myeon, Yeosu-si,
      Jeollanamdo Korea in June 2012. The fertilized eggs were pelagic eggs containing
      one oil globule, and measured 0.81~0.89 mm (0.85+/-0.04 mm, n=50) in diameter. In
      regard to rearing environment, the water temperature is 21.0~23.0 degrees C and
      the salinity is 32.0~33.20/00. Hatching was observed from 48 hours after
      fertilization, the mouth and anus of prelarvae was not opened but had egg yolk at
      newly hatched. 4 days after hatching, the mouth and anus of postlarvae was opened
      and began to eat Rotifer and was measured 2.40~2.49 mm (2.45+/-0.03 mm n=10) in
      total length. 12 days after hatching, postlarvae was measured 3.77~4.67 mm
      (4.27+/-0.33 mm) in total length, its the second pole tide of dorsal fin and the
      first pole tide of pelvic fin was extended longitudinally. 71 days after
      hatching, juvenile was measured 40.5~45.4 mm (42.6+/-2.04 mm) in total length.
      Seven bands were observed in body, and pole tides of dorsal and pelvic fins were
      shortened. 

PMID- 25949168
TI  - Spawning Behavior and Egg Development of Aplysia kurodai Inhabiting the Coastal
      Waters of Jeju Island, Korea.
AB  - This study was investigated spawning behavior, structure of egg masses and egg
      development in Aplysia kurodai inhabiting the coastal waters of Jeju Island,
      Korea. The mating and courtship behavior of A. kurodai occurred in the form of
      unilateral copulating with chain formation. In chain copulation, only the first
      animal acted as a female; the second and succeeding animals acted as males (sperm
      donors) to the animals in front and as females to the animals behind. The
      fertilized eggs were packaged in capsules that are embedded in jelly to form a
      cylindrical string called an egg masses. The number of capsule per cm of the egg
      masses was 55 to 60 capsules and each capsule within the egg masses held 15 to 25
      eggs. After spawning, the egg masses were bright yellow or orange in color. This
      egg masses color not changed until embryos developed into trochophore stage.
      Thereafter, as embryo developed from trochophore stage to veliger stage the egg
      masses color became brownish. The fertilized eggs were spherical, with a diameter
      of approximately 80+/-1 MUm at spawning. At 5 to 6 days after spawning, the
      embryo developed into trochophore stage and began to rotate within the egg
      capsule. In the trochophore stage, the precursor of the velum, called the
      prototroch or prevelum, developed. At 10 days after spawning, the prevelum is
      transformed into the velum, and the trochophore developed into veliger stage.
      Between 10 to 15 days after spawning, the veligers broke out of the egg capsule,
      and hatched as free-swimming larvae. 

PMID- 25949169
TI  - Morphometrical Changes on Korean Rose Bitterling, Rhodeus uyekii, in Early Growth
      Period.
AB  - We investigated the process of yolk absorption in Korean rose bitterling, Rhodeus
      uyekii, and determined the changes in its morphometric characteristics. The R.
      uyekii from 1 days post hatching (DPH) to 21 DPH, the eye diameter (ED) was 5.4
      at 5 DPH. Thereafter, the ED/total length (TL) ratio increased to 10.7 at 21 DPH
      (p<0.05). The yolk length (YL) decreased from 95.4 to 1.1 by 21 DPH, and this
      rate of decrease was greater than that for any other dimension (p<0.05). 12
      morphometric dimensions/TL for the R. uyekii were measured at each sampling day
      from 21 DPH to 170 DPH. At just hatching, the average TL and BW were 6.1+/-0.09
      mm and 4.9+/-0.07 mg, respectively. At 53 DPH, the average TL was 12.9+/-0.28 mm
      and the average BW was 14.7+/-0.72 mg; the total length growth equation was
      TL=5.507e(0.038t) (R (2)=0.916). Further, the body weight growth equation was
      BW=3.3647e(0.0296t) (R (2)=0.9354). The dimensions with regard to body depth
      showed the greatest growth rates in the external characteristics of the fish
      (p<0.05). The patterns of the morphometric characteristics measured in this study
      can be classified in three ways. The patterns were shown to be increased
      (y=0.0992x+ 12.07, R (2)=0.8333), decreased (y=-0.0569x+42.029, R (2)=0.8395) or
      maintained (y=0.005x+18.263, R (2)=0.3678) from 21 DPH to 170. These results will
      provide useful indices for the successful rearing of the R. uyekii. 

PMID- 25949170
TI  - Genetic distances of three mollusk species investigated by PCR analysis.
AB  - Three species of Nortamea concinua (NC) and Haliotis discus hannai (HDH) from
      Tongyeong and Sulculus diversicolor supertexta (SDS) are widely distributed on
      the coast of the Yellow Sea, southern sea and Jeju Island in the Korean Peninsula
      under the innate ecosystem. There is a need to understand the genetic traits and
      composition of three mollusk species in order to evaluate exactly the patent
      genetic effect. PCR analysis was performed on DNA samples extracted from a total
      of 21 individuals using seven decamer oligonucleotides primers. Seven primers
      were shown to generate the unique shared loci to each species and shared loci by
      the three species which could be clearly scored. A hierarchical clustering tree
      was constructed using similarity matrices to generate a dendrogram, which was
      facilitated by the Systat version 10. 236 specific loci, with an average of 56.3
      per primer, were identified in the NC species. 142 specific loci, with an average
      of 44.7 per primer, were identified in the HDH species. Especially, 126 numbers
      of shared loci by the three species, with an average of 18 per primer, were
      observed among the three species. Especially, the decamer primer BION-75
      generated 7 unique loci to each species, which were identifying each species, in
      700 bp NC species. Interestingly, the primer BION-50detected 42 shared loci by
      the three species, major and/or minor fragments of sizes 100 bp and 150 bp,
      respectively, which were identical in all samples. As regards average bandsharing
      value (BS) results, individuals from HDH species (0.772) exhibited higher
      bandsharing values than did individuals from NC species (0.655). In this study,
      the dendrogram obtained by the seven decamer primers indicates three genetic
      clusters: cluster 1 (CONCINNA 01~CONCINNA 07), cluster 2 (HANNAI 08~HANNAI 14),
      cluster 3 (SUPERTEXTA 15~SUPERTEXTA 21). Comparatively, individuals of HDH
      species were fairly closely related to that of SDS species, as shown in the
      hierarchical dendrogram of genetic distances. 

PMID- 25949171
TI  - Histological Analysis of Early Gonadal Development and Sex Differentiation in
      Chameleon Goby, Tridentiger trigonocephalus.
AB  - This study describes the developmental process of gonads in chameleon goby,
      Tridentiger trigonocephalus from the stage of hatching to 100 days after hatching
      (DAH). Based on histological observation, the primordial germ cells were observed
      in mesentery between mesonephric duct and gut at 15 DAH (total length, TL: 6.8+/
      0.2 mm). At 20 DAH (TL: 7.9+/-0.1 mm), the primordial gonad began to protrude
      into peritoneal cavity and developed between mesonephric duct and gut. Initial
      ovarian differentiation was identified by the presence of ovarian cavity and
      oogonia in the gonads at 55 DAH (TL: 21.1+/-1.3 mm). Testicular differentiation
      started at 65 DAH (TL: 23.7+/-0.9 mm) with appearance of spermatogonial cells in
      the gonads. These findings indicate that sex differentiation in T.
      trigonocephalus occurs earlier in females than males, suggesting that this
      species can be classified as an undifferentiated gonochorist. 

PMID- 25949172
TI  - The Potential Regressive Role of Syzygium aromaticum on the Reproduction of Male
      Golden Hamsters.
AB  - The flower buds of Syzygium aromaticum (clove) have been used as traditional
      medicine for the treatment of male sexual disorders in Asian countries. Recently,
      there are some reports about the effects of the clove on reproductive activities
      in mammals. Therefore, its effect on testicular function was examined in male
      golden hamsters whose reproductive activity is inhibited by photoperiod such as
      winter climate. The male animals were given by daily oral administrations (56
      consecutive days) in three doses (4 mg, 20 mg, and 100 mg/kg BW) of the alcoholic
      extract of the clove. Generally lower dose (4 mg) of the extract continued to
      keep the reproductive activities of testes. The both middle and high doses (20 mg
      and 100 mg) of the extract completely inhibited the testicular activity in some
      animals. Taken together, these results suggest a possible biphasic action of
      alcoholic extract of Syzygium aromaticum flower bud on testicular function. 

PMID- 25949173
TI  - Polo-like kinases (plks), a key regulator of cell cycle and new potential target
      for cancer therapy.
AB  - Cell cycle process is regulated by a number of protein kinases and among them,
      serine/threonine kinases carry phosphate group from ATP to substrates. The most
      important three kinase families are Cyclin-dependent kinase (Cdk), Polo-like
      kinase (Plk), and Aurora kinase. Polo-like kinase family consists of 5 members
      (Plk1-Plk5) and they are involved in multiple functions in eukaryotic cell
      division. It regulates a variety of aspects such as, centrosome maturation,
      checkpoint recovery, spindle assembly, cytokinesis, apoptosis and many other
      features. Recently, it has been reported that Plks are related to tumor
      development and over-expressed in many kinds of tumor cells. When injected the
      anti-Plk antibody into human cells, the cells show aneuploidy, and if inhibit
      Plks, most of the mitotic cell division does not proceed properly. For that
      reasons, many inhibitors of Plk have been recently emerged as new target for
      remedy of the cancer therapeutic research. In this paper, we reviewed briefly the
      characteristics of Plk families and how Plks work in regulating cell cycles and
      cancer formation, and the possibilities of Plks as target for cancer therapy. 

PMID- 25949174
TI  - Indirect Evidence on Sex Reversal of Sinonovacula constricta (Bivalvia:
      Euheterodonta) and Gomphina veneriformis (Bivalvia: Veneridae).
AB  - This study attempts to propose the possibility of the sex reversal in
      Sinonovacula constricta and Gomphina veneriformis by confirming the changes in
      the sex ratio with the shell length in the same population level. For analysis of
      sex ratio, 100 individuals of S. constricta (SL 26.5-95.0 mm) and 2385
      individuals of G. veneriformis (SL 15.1-60.1 mm) were used. Sex was analyzed
      histologically. Both species displayed the tendency of increase in the female
      proportion with increase in shell length. In this study, changes in the sex ratio
      in accordance with the growth of S. constricta and G. veneriformis are determined
      to be indirect evidence that signifies their sex reversal. 

PMID- 25949175
TI  - Morphological Analysis of Blind-Side Hypermelanosis of the Starry Flounder,
      Platichthys stellatus during Early Development.
AB  - In Pleuronectiformes, blind-side malpigmentation (hypermelanosis) is common in
      cultured flatfishes, and is economically important. To understand the mechanism
      of blind-side hypermelanosis in flatfishes, we examined when the malpigmentation
      initially occurred, and studied how the symptoms proceeded during early
      development of the starry flounder, Platichthys stellatus. To assess quantitative
      pattern changes of blind-side skin, we observed morphological development of the
      whole body from 22 (total length [TL] 10.0+/-0.2 mm and body weight [BW] 8.8+/
      0.57 mg) to 110 days (TL 23.4+/-0.7 mm, BW 193.6+/-23.3 mg) after hatching (DAH),
      and also examined the malpigmented area rate of blind-side skin and the
      malpigmented fish ratios. The experimental animals were reared in fiberglass
      reinforced plastic (FRP) tanks in water at a temperature of 18.9+/-1.9 degrees C
      and salinity of 32.6+/-0.6 psu and were fed with rotifer and Artemia nauplii from
      22 to 48 DAH, and with A. nauplii and commercial feed from 49 to 110 DAH. As
      results, the first staining patch seen by the naked eye was observed around the
      area between the anus and pelvic fin or caudal edge of the trunk at 80 DAH (TL
      20.6+/-0.5 mm, BW 112.5+/-8.8 mg). The pigmented area and the pigmented fish
      ratios were significantly increased from 80 to 110 DAH. These results indicated
      that malpigmentation on the blind side of starry flounder was initially observed
      at about 2 cm in length and 100 mg in weight, and the pigmented domain on the
      blind-side skin was continually broadened by the differentiation of pigmented
      cells (melanophores and xanthophores) with growth. 

PMID- 25949176
TI  - Genetic Distances of Three White Clam (Meretrix lusoria) Populations Investigated
      by PCR Analysis.
AB  - The twenty-one individuals of Meretrix lusoria were secured from Gunsan, Shinan
      and Yeonggwang on the coast of the Yellow Sea and the southern sea in the Korean
      Peninsula, respectively. Amplification of a single COI fragment (720 bp) was
      imagined, and no apparent size differences were observed in amplified fragments
      between Meretrix lusoria and M. petechialis individuals. The size of the DNA
      fragments also varied excitedly, from 200 to 1,600 bp. The oligonucleotides
      primer BION-08 produced the least loci (a total of 17), with an average of 2.43
      in the Gunsan population, in comparison to the other primers used. Remarkably,
      the primer BION-13 detected 42 shared loci by the three populations, major and/or
      minor fragments of sizes 200 bp and 400 bp, respectively, which were identical in
      all samples. The dendrogram gained by the seven oligonucleotides primers
      highlight three genetic clusters: cluster 1 (GUNSAN 01 ~ GUNSAN 07), cluster 2
      (SHINAN 08 ~ SHINAN 14) and cluster 3 (YEONGGWANG 15 ~ YEONGGWANG 21). The
      longest genetic distance among the twenty-one Meretrix lusoria individuals that
      displayed significant molecular differences was between individuals GUNSAN no. 01
      and SHINAN no. 14 (genetic distance = 0.574). Comparatively, individuals of
      SHINAN population were fairly closely related to that of YEONGGWANG population.
      In this study, PCR analysis has discovered significant genetic distances between
      two white clam population pairs (P<0.05). 

PMID- 25949177
TI  - RAG-1 and IgM Genes, Markers for Early Development of the Immune System in Olive
      Flounder, Paralichthys olivaceus.
AB  - Fish larvae are immediately exposed to microbes from hatching to maturation of
      their lymphoid organs, therefore effective innate mechanisms is very important
      for survival. However, the knowledge of the development of immune system in fish
      is limited and in demand now. In vertebrates, recombination-activating gene 1
      (RAG-1) and immunoglobulin M (IgM) have been considered as very useful markers of
      the physiological maturity of the immune system. In this study, the expression of
      the both genes was assessed throughout the early developmental stages of olive
      flounder larvae (5-55 dph) and used as markers to follow the development of
      immune system. RAG-1 and IgM mRNA expression was detectable at 5 dph and remained
      so until 55 dph. These patterns of expression may suggest that the olive flounder
      start to develop its function around 5 dph. Tissue distribution was found that
      both genes mRNAs are only expressed in the immune-related organ such as spleen,
      kidney and gill. The early detection of IgM mRNA led to the investigation of its
      presence in oocytes. Both RAG-1 and IgM mRNA transcripts were detected in
      unfertilized oocytes, suggesting that they are maternally transferred. The
      biological significance of such a phenomenon remains to be investigated. 

PMID- 25949178
TI  - Expression of Vimentin Intermediate Filament for Vascular Development in Olive
      Flounder (Paralichthys olivaceus).
AB  - Cardiovascular system is the primary organ to develop and reach a functional
      state, which underscores the essential role of the vasculature in the developing
      embryo. The vasculature is a highly specialized organ that functions in a number
      of key physiological works including the carrying of oxygen and nutrients to
      tissues. It is closely involved in the formation of heart, and hence it is
      essential for survival during the hatching period. The expression of genes
      involved during vascular development in the olive flounder (Paralichthys
      olivaceus) in the days after hatching is not fully understood. Therefore, we
      examined the expression patterns of genes activated during the development of
      flounder. Microscopic observations showed that formation of blood vessels is
      related to the expression of the vimentin gene. Also, the temporal expression
      patterns of this vimentin-like gene in the developmental stages and in the normal
      tissues of olive flounder. The purpose of this study was to examine the
      expression patterns of vimentin in normal tissues of the olive flounder and
      during the development of the vascular system in newly hatched olive flounders
      and HIF-1 plays a vital role in the formation of blood vessels during
      development. Vimentin expression was strong at the beginning of the development
      of blood vessels, and was present throughout all developmental stages. Our
      findings have important implications with respect to the roles of vimentin and
      HIF-1 in the development and evolution of the first blood vessels in olive
      flounder. Further studies are required to elucidate the vimentin-mediated hypoxic
      response signal transduction and to decipher the functional role of vimentin in
      developmental stages. 

PMID- 25949179
TI  - Improvement of the vitrification method suppressing the disturbance of meiotic
      spindle and chromosome systems in mature oocytes.
AB  - Vitrification method is widely used in oocyte cryopreservation for IVF but the
      birth rates are lower than that of the fresh oocyte. One of the known main
      reasons is structural instability of meiotic spindle and chromosome systems of
      mature oocyte. To get the best way for keeping competence of matured oocytes, we
      studied the best conditions for vitrification focused on equilibration times. The
      mature oocytes were underwent vitrification with current popular method and
      analyzed the survival rates, microtubule stability and DNA integrity. The
      survival rates of recovered oocyte are almost same between groups and are more
      than 93%. The structural configuration of meiotic spindle was well kept in 10 min
      equilibration group and the stability rate was almost same with that of control.
      The chromosomal breakdown was observed in all experimental groups, but the
      chromosomal stability was higher in 10 min equilibration group than the other
      groups. The 10 min equilibration group showed best condition compared with the
      other groups. Based on these results, the equilibration time is one of the key
      factors in successful keeping for competence of mature oocyte. Although, more
      fine analysis about the effects of physical stress on oocyte during vitrification
      is needed to define the optimal condition, it is suggested that the optimal
      equilibration time to get competent oocyte in mouse is 10 min. Information
      acquired this study may provide insight into intracellular structural events
      occurring in human oocytes after vitrification and application for
      cryopreservation of human oocyte. 

PMID- 25949180
TI  - Induction of Primary Male in Juvenile Red Spotted Grouper Epinephelus akaara by
      Immersion of 17alpha-Methyltestosterone.
AB  - We investigated the androgenic effects of 17alpha- methyltestosterone (MT) on
      gonadal sex reversal in juvenile red spotted grouper Epinephelus akaara. The fish
      were immersed in 17alpha-MT at 1 and 5 mg/L. Treatment method of 17alpha-MT was
      once weekly for 4 and 8 weeks. Fish were sampled at 12 months after end of the
      treatment period in order to histological analysis. At the initiation of an
      experiment (70 day after hatching), juvenile red spotted grouper have the paired
      primordial gonads with somatic cells bellow kidney in the posterior portion of
      the body cavity. Formation of ovarian cavity indicates that the ovarian
      differentiation beginning at 70 DAH in red spotted grouper. At 12 months after
      end of the treatment period, control group, 17alpha-MT 1 mg/L treatment group for
      4 and 8 weeks, and 17alpha-MT 5 mg/L treatment group for 4 weeks were all female.
      However, sex-changed males without ovarian cavity were observed in the 17alpha-MT
      5 mg/L treatment group for 8 weeks. In grouper, we firstly reported that the red
      spotted grouper be able to induce the primary males by hormone treatment prior to
      gonadal sex differentiation. 

PMID- 25949181
TI  - Effect of Water Temperature and Photoperiod on Final Oocyte Maturation in Red
      Marbled Rockfish, Sebastiscus tertius.
AB  - Rearing experiments were conducted using several regimes combined with different
      photoperiods and water temperatures to investigate the role of temperature and
      photoperiod as environmental cues regulating reproduction in red marbled
      rockfish, Sebastiscus tertius. The initial gonadosomatic index (GSI) was 1.62+/
      0.32% and that in the 15 degrees C control was 7.01+/-0.46% at the end of the
      experiment. The highest GSI was 9.10 +/- 0.35% in the 12L:12D photoperiod-treated
      fish. The highest GSI at 19 degrees C was 15.03+/-0.86% in the 12L:12D
      photoperiod treatment. The initial hepatosomatic index (HSI) was 3.09+/-0.72% and
      that in the 15 degrees C control was 3.88 +/- 0.45%. The highest HSI was 4.00 +/-
      0.56% in the 15L:9D treated fish. The highest HSI at 19 degrees C was 4.05+/
      0.63% in the 12L:12D treated fish. 

PMID- 25949182
TI  - Studies of In Vitro Embryo Culture of Guppy (Poecilia reticulata).
AB  - Different with other fishes, the guppies (Poecilia reticulata) is ovoviviparity,
      which retain their fertilized eggs within the follicle throughout gestation. The
      synchronously growing diplotene oocytes store nutrients in droplets and yolk,
      before their maturation and fertilization. The lecithotrophic strategy of
      development entails the provisioning of embryos with resources from the maternal
      yolk deposit rather than from a placenta, it allows the extracorporeal culture of
      guppy embryo. Studies on their early development of live bearers like the guppy
      including lineage tracing and genetic manipulations, have been limited.
      Therefore, to optimize conditions of embryo in vitro culture, explanted embryos
      from pregnant females were incubated in embryo medium (L-15 medium, supplemented
      with 5, 10, 15, 20% fetal bovine serum, respectively). We investigated whether
      the contents of FBS in vitro culture medium impact the development of embryos,
      and whether they would hatch in vitro. Our study found that in 5% of FBS of the
      medium, although embryos developed significantly slower in vitro than in the
      ovary, it was impossible to exactly quantify the developmental delay in culture,
      due to the obvious spread in developmental stage within each batch of eggs, and
      embryos can only be maintained until the early-eyed. And although in culture with
      20% FBS the embryos can sustain rapid development of early stage, but cannot be
      cultured for the entire period of their embryonic development and ultimately
      died. In the medium with 10% and 15% FBS, the embryos seems well developed, even
      some can continue to grow after follicle ruptures until it can be fed. We also
      observed that embryonic in these two culture conditions were significantly
      different in development speed, in 15% it is faster than 10%. But 10% FBS appears
      to be more optimizing condition than 15% one on development process of embryos
      and survival rate to larvae stage. 

PMID- 25949183
TI  - Ovarian Features after 2 Weeks, 3 Weeks and 4 Weeks Transdermal Testosterone Gel
      Treatment and Their Associated Effect on IVF Outcomes in Poor Responders.
AB  - This study was performed to investigate the effect of of transdermal testosterone
      gel (TTG) on controlled ovarian stimulation (COS) and IVF outcomes and ovarian
      morphology according to pretreatment duration in poor responders. A total of 120
      women were recruited for this pilot study. They were randomized into control, 2
      weeks, 3 weeks or 4 weeks TTG treatment groups. For three TTG treatment groups,
      12.5 mg TTG was applied daily for 2 weeks, 3 weeks or 4 weeks in preceding period
      of study stimulation cycle. After 3 weeks of TTG pretreatment, significant
      increase of antral follicle count (AFC) and significant decreases of mean
      follicular diameter (MFD) and resistance index (RI) value of ovarian stromal
      artery were observed (p=0.026, p<0.001, p<0.01, respectively). The total dose of
      rhFSH administered for COS significantly decreased after 3 and 4 weeks TTG
      treatment both compared with control group (p<0.001, p<0.001). The numbers of
      oocytes retrieved and mature oocytes were significanty higher in 3 and 4 weeks
      TTG treatment groups than control group (p<0.001, p<0.001 in the number of
      oocytes retrieved; p<0.001, p<0.001 in the number of mature oocytes). The
      clinical pregnancy rate and live birth rate were increased only in 4 weeks TTG
      treatment group compared with control group (p=0.030 and p=0.042, respectively).
      These data demonstrated that TTG pretreatment for 3 to 4 weeks increases AFC and
      ovarian stromal blood flow, thereby potentially improving the ovarian response to
      COS and IVF outcome in poor responders undergoing IVF/ICSI. 

PMID- 25949184
TI  - Adaptive Transition of Aquaporin 5 Expression and Localization during
      Preimplantation Embryo Development by In Vitro Culture.
AB  - Adaptive development of early stage embryo is well established and recently it is
      explored that the mammalian embryos also have adaptive ability to the stressful
      environment. However, the mechanisms are largely unknown. In this study, to
      evaluate the possible role of aquaporin in early embryo developmental adaptation,
      the expression of aquaporin (AQP) 5 gene which is detected during early
      development were examined by the environmental condition. To compare expression
      patterns between in vivo and in vitro, we conducted quantitative RT-PCR and
      analyzed localization of the AQP5 by whole mount immunofluorescence. At in vivo
      condition, Aqp5 expressed in oocyte and in all the stages of preimplantation
      embryo. It showed peak at 2-cell stage and decreased continuously until morula
      stage. At in vitro condition, Aqp5 expression pattern was similar with in vivo
      embryos. It expressed both at embryonic genome activation phase and second
      midpreimplantation gene activation phase, but the fold changes were modified
      between in vivo embryos and in vitro embryos. During in vivo development, AQP5
      was mainly localized in apical membrane of blastomeres of 4-cell and 8-cell stage
      embryos, and then it was localized in cytoplasm. However, the main localization
      area of AQP5 was dramatically shifted after 8-cell stage from cytoplasm to
      nucleus by in vitro development. Those results explore the modification of Aqp5
      expression levels and location of its final products by in vitro culture. It
      suggests that expression of Aqp5 and the roles of AQP5 in homeostasis can be
      modulated by in vitro culture, and that early stage embryos can develop
      successfully by themselves adapting to their condition through modulation of the
      specific gene expression and localization. 

PMID- 25949185
TI  - Effect of Long Term Reverse Feeding on the Reproductive and Non-reproductive
      Tissues in Male Mice.
AB  - Previously, we demonstrated that the shift and/or restriction of feeding time
      during relatively short-term period (4 weeks) could alter the pituitary
      gonadotropin expression and the weights of seminal vesicle and prostate in rats.
      We also found that the reverse feeding (RF) schedule (up to 8 weeks) might induce
      an adaptable metabolic stress and cause impairment of androgen-dependent
      reproductive tissues. In the present study, we extended the RF time regimen up to
      12 weeks, and measured the reproductive tissue weights. After 4 and 8 weeks of
      RF, the weights of epididymis were not significantly different. After 12 weeks,
      however, epididymis weights of RF animals were significantly different (CON 12W :
      RF 12W = 48.26+/-0.62 mg : 44.05+/-1.57 mg, p<0.05). After 4 and 12 weeks of
      feeding, seminal vesicle weights of RF animals were significantly decreased (CON
      4W : RF 4W = 79.36+/-8.34 mg : 46.28+/-2.43 mg, p<0.001; CON 12W : RF 12W =
      72.04+/-3.76 mg : 46.71+/-2.27 mg, p<0.001, respectively). Prostate weights were
      not changed by RF. Kidney and spleen weights of RF animals were significantly
      different on weeks 4 and 12 (Kidney, CON 4W : RF 4W = 249.72+/-4.20 mg : 228.41+/
      3.03 mg, p<0.001; CON 12W : RF 12W = 309.15+/-7.49 mg : 250.72+/-6.13 mg,
      p<0.001, respectively, Spleen, CON 4W : RF 4W = 111.26+/-3.76 mg : 96.88+/-4.69
      mg, p<0.05; CON 12W : RF 12W = 123.93+/-10.72 mg : 94.68+/-5.65 mg, p<0.05,
      respectively). Histology analysis of seminal vesicle revealed that the thinner
      epithelial cell layers, reduced complexities of swollen papilla folding in the
      exocrine glands on weeks 4 and 12 of RF. There was no histological difference
      between control and RF group on week 8. The present study indicates that up to 12
      weeks RF induced differential changes in tissue weights of male mice. In
      particular, seminal vesicle, kidney and spleen seemed to temporarily adapted to
      the RF-induced metabolic stress on week 8 of feeding schedule. These results
      confirmed the our previous study that the RF might induce an adaptable metabolic
      stress and cause impairment of androgen-dependent reproductive tissues such as
      epididymis and seminal vesicle as well as non-reproductive tissues such as kidney
      and spleen. Further studies will be needed to achieve a better understanding of
      the how does mealtime shift affect the reproductive function and exact nature of
      adaptation. 

PMID- 25949186
TI  - Genetic distances and variations of three geographic hairtail populations
      identified by PCR analysis.
AB  - In the present study, muscle tissues were obtained separately from individuals
      from Atlantic hairtail population (AHP), Gunsan hairtail population (GHP) and
      Chinese hairtail population (CHP), respectively. The seven decamer primers were
      used to generate the shared loci, specific, unique shared loci to each population
      and shared loci by the three hairtail populations. Here, averagely, a decamer
      primer generated 64.7 amplified products per primer in the AHP population, 55.7
      in GHP population and 56.4 in CHP population. The number of unique shared loci to
      each population and number of shared loci by the three populations generated by
      genetic analysis using 7 decamer primers in AHP, GHP and CHP population. 119
      unique shared loci to each population, with an average of 17 per primer, were
      observed in the AHP population, and 28 loci, with an average of 4 per primer,
      were observed in the CHP population. The hierarchical dendrogram point out three
      main branches: cluster 1 (ATLANTIC 01 ~ ATLANTIC 07), cluster 2 (GUNSAN 08 ~
      GUNSAN 14) and cluster 3 (CHINESE 15 ~ CHINESE 21). The shortest genetic distance
      displaying significant molecular difference was between individuals' CHINESE no.
      16 and CHINESE no. 18 (0.045). In the long run, individual no. 01 of the AHP
      population was most distantly related to CHINESE no. 19 (genetic distance =
      0.430). Consequently, PCR analysis generated on the genetic data displayed that
      the geographic AHP population was widely separated from CHP population, while
      individuals of CHP population were fairly closely related to those of GHP
      population. 

PMID- 25949187
TI  - Egg Development and Morphology of Larva and Juvenile of the Oryzias latipes.
AB  - In order to monitor the developmental features of embryos, larvae, and juveniles
      of Oryzias latipes (Temminck and Schlegel), Oryzias latipes was caught in river
      of Shinduck-dong, Yeosu-si, Jeollanam-do, on May 2011, and experiments were
      carried out in Ichthyology laboratory at Chonnam National University. The
      blastodisc step was the first level for natural spawning. The optic vesicle,
      Kupffer's vesicle, myotome began to appear 75 hours 57 minutes later. After
      blastodisc development, the pectoral fins were made at 143 hours 37 minutes and
      the tail was separated started at the same time. Hatching was observed at 167
      hours 27 minutes after blastodisc. The total length of the hatched larvae was
      4.95~5.10 mm (mean, 5.01 mm), the mouth and anus were opened. Larvae used yolk
      completely after 3 days after hatching. The total length larvae was 5.45~5.56 mm
      (mean, 5.52 mm) after 8 days after hatching, and appeared the stems for tail. The
      stems pectoral, anal fin were showed after 14 days and the stems dorsal, ventral
      fin were appeared after 19 days. For 35 days after hatching, the total length of
      larvae 13.95~15.30 mm (mean, 14.64 mm), and at this time, fins and body were
      transferred like the adult Oryzias latipes. 

PMID- 25949188
TI  - Spermiogenesis and Taxonomical Values of Sperm Ultrastructures in Male
      Crassostrea ariakensis (Fujita & Wakiya, 1929) (Pteroirmorphia: Ostreidae) in the
      Estuary of the Seomjin River, Korea.
AB  - Characteristics of the developmental stages of spermatids during spermiogenesis
      and phylogenetic classicfication of the species using sperm ultrastructures in
      male Crassostrea ariakensis were investigated by transmission electron microscope
      observations. The morphology of the spermatozoon of this species has a primitive
      type and is similar to those of Ostreidae. Ultrastructures of mature sperms are
      composed of broad, modified cap-shaped acrosomal vesicle and an axial rod in
      subacrosomal materials on an oval nucleus, four spherical mitochondria in the
      sperm midpiece, and satellite fibres which appear near the distal centriole. The
      axoneme of the sperm tail shows a 9+2 structure. Accordingly, the ultrastructural
      characteristics of mature sperm of C. ariakensis resemble to those of other
      investigated ostreids in Ostreidae in the subclass Pteriomorphia. In this study,
      particularly, two transverse bands (stripes) appear at the anterior region of the
      acrosomal vesicle of this species, unlike two or three transverse bands (stripes)
      in C. gigas. It is assumed that differences in this acrosomal substructure are
      associated with the inability of fertilization between the genus Crassostrea and
      other genus species in Ostreidae. Therefore, we can use sperm ultrastructures and
      morphologies in the resolution of taxonomic relationships within the Ostreidae in
      the subclass Pteriomorphia. These spermatozoa, which contain several
      ultrastructures such as acrosomal vesicle, an axial rod in the sperm head part
      and four mitochondria and satellite fibres in the sperm midpiece, belong to the
      family Ostreidae in the subclass Pteriomorphia. 

PMID- 25949189
TI  - Disturbance in testosterone production in leydig cells by polycyclic aromatic
      hydevrepocarbons.
AB  - Polycyclic aromatic hydevrepocarbons (PAHs), which are ubiquitous in the air, are
      present as volatile and particulate pollutants that result from incomplete
      combustion. Most PAHs have toxic, mutagenic, and/or carcinogenic properties.
      Among PAHs, benzo[a]pyrene (B[a]P) and dimethylbenz[a]anthracene (DMBA) are
      suspected endocrine disruptors. The testis is an important target for PAHs, yet
      effects on steroidogenesis in Leydig cells are yet to be ascertained.
      Particularly, disruption of testosterone production by these chemicals can result
      in serious defects in male reproduction. Exposure to B[a]P reduced serum and
      intratesticular fluid testosterone levels in rats. Of note, the testosterone
      level reductions were accompanied by decreased steroidogenic acute regulatory
      protein (StAR) and 3beta-hydevrepoxysteroid dehydevrepogenase isomerase (3beta
      HSD) expression in Leydig cells. B[a]P exposure can decrease epididymal sperm
      quality, possibly by disturbing the testosterone level. StAR may be a key
      steroidogenic protein that is targeted by B[a]P or other PAHs. 

PMID- 25949191
TI  - Expression of tight junction molecule in the human serum-induced aggregation of
      human abdominal adipose-derived stem cells in vitro.
AB  - Previously we have shown that human abdominal adipose derived-stem cells (ADSCs)
      could aggregate during the high-density culture in the presence of human serum
      (HS). In the present study, we observed that human cord blood serum (CBS) and
      follicular fluid (HFF) also induced aggregation. Similarly, porcine serum could
      induce aggregation whereas bovine and sheep sera induced little aggregation. qRT
      PCR analyses demonstrated that, compared to FBS-cultured ADSCs, HScultured cells
      exhibited higher level of mRNA expression of CLDN3, -6, -7, -15, and -16 genes
      among the tight junction proteins. ADSCs examined at the time of aggregation by
      culture with HS, BSA, HFF, CBS, or porcine serum showed significantly higher
      level of mRNA expression of JAM2 among JAM family members. In contrast, cells
      cultured in FBS, bovine serum or sheep serum, showed lower level of JAM2
      expression. Immunocytochemical analyses demonstrated that the aggregates of HS
      cultured cells (HS-Agg) showed intense staining against the anti-JAM2 antibody
      whereas neither non-aggregated cells (HS-Ex) nor FBS-cultured cells exhibited
      weak staining. Western blot results showed that HS-Agg expressed JAM2 protein
      more prominently than HS-Ex and FBS-cultured cells, both of latter reveled weaker
      intensity. These results suggest that the aggregation property of ADSCs during
      high-density culture would be dependent on the specific components of serum, and
      that JAM2 molecule could play a role in the animal sera-induced aggregation in
      vitro. 

PMID- 25949192
TI  - Biphasic activity of chloroquine in human colorectal cancer cells.
AB  - Autophagy is a homeostatic degradation process that is involved in tumor
      development and normal development. Autophagy is induced in cancer cells in
      response to chemotherapeutic agents, and inhibition of autophagy results in
      enhanced cancer cell death or survival. Chloroquine (CQ), an anti-malarial
      devrepug, is a lysosomotropic agent and is currently used as a potential
      anticancer agent as well as an autophagy inhibitor. Here, we evaluate the
      characteristics of these dual activities of CQ using human colorectal cancer cell
      line HCT15. The results show that CQ inhibited cell viability in dose-and time
      dependent manner in the range between 20 to 80 uM, while CQ did not show any
      antiproliferative activity at 5 and 10 uM. Cotreatment of CQ with antitumor agent
      NVP-BEZ235, a dual inhibitor of PI3K/mTOR, rescued the cell viability at low
      concentrations meaning that CQ acted as an autophagy inhibitor, but CQ induced
      the lethal effect at high concentrations. Acridine orange staining revealed that
      CQ at high doses induced lysosomal membrane permeabilization (LMP). High doses of
      CQ produced cellular reactive oxygen species (ROS) and cotreatment of
      antioxidants, such as NAC and trolox, with high doses of CQ rescued the cell
      viability. These results suggest that CQ may exert its dual activities, as
      autophagy inhibitor or LMP inducer, in concentration-dependent manner. 

PMID- 25949190
TI  - A New Paradigm to Mitigate Osteosarcoma by Regulation of MicroRNAs and
      Suppression of the NF-kappaB Signaling Cascade.
AB  - Osteosarcoma (OS) is one of the most common malignant primary bone tumors and NF
      kappaB appears to play a causative role, but the mechanisms are poorly
      understood. OS is one of the pleomorphic, highly metastasized and invasive
      neoplasm which is capable to generate osteoid, osteoclast and osteoblast matrix.
      Its high incidence has been reported in adolescent and childevrepen. Cell signal
      cascade is the pivotal functional mechanism acquired during the differentiation,
      proliferation, growth and survival of the cells in neoplasm including OS. The
      major limitation to the success of chemotherapy in OS is the development of
      multidevrepug resistance (Mdevrep). Answers to all such queries might come from
      the knock-in experiments in which the combined approach of miRNAs with NF-kappaB
      pathway is put into use. Abnormal miRNAs can modulate several epigenetical
      switching as a hallmark of number of diseases via different cell signaling.
      Studies on miRNAs have opened up the new avenues for both the diagnosis and
      treatment of cancers including OS. Collectively, through the present study an
      attempt has been made to establish a new systematic approach for the
      investigation of microRNAs, biophysiological factors and their target pairs with
      NF-kappaB to ameliorate oncogenesis with the "bridge between miRNAs and NF
      kappaB". The application of NF-kappaB inhibitors in combination with miRNAs is
      expected to result in a more efficient killing of the cancer stem cells and a
      slower or less likely recurrence of cancer. 

PMID- 25949193
TI  - Expression Pattern of Early Growth Response Gene 1 during Olive Flounder
      (Paralichthys olivaceus) Embryonic Development.
AB  - The early growth response protein 1 (Egr-1) is a widely reported zinc finger
      protein and a well known transcription factor encoded by the Egr-1 gene, which
      plays key roles in many aspects of vertebrate embryogenesis and in adult
      vertebrates. The Egr-1 expression is important in the formation of the gill
      vascular system in flounders, which develops during the post-hatching phase and
      is essential for survival during the juvenile period. However, the complete
      details of Egr-1 expression during embryo development in olive flounder are not
      available. We assessed the expression patterns of Egr-1 during the early
      development of olive flounders by using reverse transcription polymerase chain
      reaction (RT-PCR) analysis. Microscopic observations showed that gill filament
      formation corresponded with the Egr-1 expression. Thus, we showed that Egr-1
      plays a vital role in angiogenesis in the gill filaments during embryogenesis.
      Further, Egr-1 expression was found to be strong at 5 days after hatching (DAH),
      in the development of the gill vascular system, and this strong expression level
      was maintained throughout all the development stages. Our findings have important
      implications with respect to the biological role of Egr-1 and evolution of the
      first respiratory blood vessels in the gills of olive flounder. Further studies
      are required to elucidate the Egr-1-mediated stress response and to decipher the
      functional role of Egr-1 in developmental stages. 

PMID- 25949194
TI  - Spawning Behavior, Egg Development, Larvae and Juvenile Morphology of
      Hyphessobrycon eques (Pisces: Characidae) Characidae Fishes.
AB  - Hyphessobrycon eques is a famous fish for ornamental fish market and aquarium.
      They are inhabit in regions of Amazon and Paraguay River basin. Serpae fishs were
      investigated 2-3 males are chased to female, and then males attempted to simulate
      the females abdomen. After fertilization, eggs were kept in incubators at 28
      degrees C. The fertilized eggs had adhesive and demesal characteristics and had a
      mean diameter of 0.92 +/- 0.01 mm. Larvae hatched at 16 hrs post fertilization.
      The hatched larvae averaged 2.90 +/- 0.16 mm in total length (LT ). Complete yolk
      sac resorption and mouth opening occurred on the third day post hatching. At 45
      days post hatching, the larvae were 12.5 +/- 1.60 mm LT and had reached the
      juvenile stage. 

PMID- 25949195
TI  - Fish Myogenic Regulatory Protein LUC7L: Characterization and Expression Analysis
      in Korean Rose Bitterling (Rhodeus uyekii).
AB  - Serine-arginine-rich nuclear protein LUC7L plays an important role in the
      regulation of myogenesis in mice. In the present study, we isolated and
      characterized the Korean rose bitterling Rhodeus uyekii Luc7l cDNA, designated
      RuLuc7l. The RuLuc7l cDNA is 1,688 bp long and encodes a 364-amino-acid
      polypeptide containing serine/arginine-rich region at the C-terminus. The deduced
      RuLuc7l protein has high amino acid identity (71-97%) with those of other species
      including human. Phylogenetic analysis revealed that RuLUC7L clustered with fish
      LUC7L proteins. The expression of RuLuc7l mRNA was high in the brain, kidney, and
      stomach of Korean rose bitterling. Expression of the RuLuc7l mRNA was detected
      from 1 day post-fertilization (dpf) and moderately increased until 21 dpf during
      the early development. Further investigations are required to elucidate the
      functional role of RuLUC7L in myogenesis in R. uyekii. 

PMID- 25949196
TI  - Egg Development and Early Life History of Korean Endemic Species Korean Spotted
      Sleeper, Odontobutis interrupta (Pisces: Odontobutidae).
AB  - The egg development and early life history of Korean spotted sleeper, Odontobutis
      interrupta which is Korean endemic species from Sora-choen was investigated. The
      Korean spotted sleeper were caught at Sora-myeon, Yeosu-si, Jeollanamdo, from
      Korea at May in 2014. The fertilized eggs were 4.23 +/- 0.05 mm in long diameter
      and had oil globules. Hatching time of the embryo began about 442 hr 14 min after
      fertilization under water temperature of 19.5 degrees C. The newly hatched larvae
      were 4.27 +/- 0.35 mm in total length and their anus were not yet opened. 3 days
      after hatching postlarvae was measured 6.20 +/- 0.11 mm in total length. 10 days
      after hatching postlarvae was measured 6.69 +/- 0.14 mm in total length. 

PMID- 25949197
TI  - Transcriptional Onset of Lysozyme Genes during Early Development in Olive
      Flounder (Paralichthys olivaceus).
AB  - The immune system in teleost fish is not completely developed during embryonic
      and larval stages, therefore effective innate mechanisms is very important for
      survival in such an environment. However, the knowledge of the development of
      immune system assumed to be restricted. In many species, lysozymes have been
      considered as important genes of the first line immune defense. The early
      detection of lysozyme mRNA in previous reports, led to the investigation of its
      presence in oocytes. As a result, c-type lysozyme mRNA transcripts were detected
      in unfertilized oocytes indicating maternal transfer. Therefore, we investigated
      the expression patterns of lysozymes in flounder, including the matured oocyte.
      In our results, c-type lysozyme mRNA was first detected in unfertilized oocyte
      stage, observed the significantly decreased until hatching stage, and was
      significantly increased after hatching stage. On the other hand, g-type lysozyme
      mRNA transcripts were first detected at late neurula stage, and the mRNA level
      was significantly increased after 20 dph. It may be suggest that maternally
      supplied mRNAs are selectively degraded prior to the activation of embryonic
      transcription. This study will be help in understanding the maturation and onset
      of humoral immunity during development of olive flounder immune system. 

PMID- 25949198
TI  - Development and Validation of Single Nucleotide Polymorphism (SNP) Markers from
      an Expressed Sequence Tag (EST) Database in Olive Flounder (Paralichthys
      olivaceus).
AB  - To successful molecular breeding, identification and functional characterization
      of breeding related genes and development of molecular breeding techniques using
      DNA markers are essential. Although the development of a useful marker is
      difficult in the aspect of time, cost and effort, many markers are being
      developed to be used in molecular breeding and developed markers have been used
      in many fields. Single nucleotide polymorphisms (SNPs) markers were widely used
      for genomic research and breeding, but has hardly been validated for screening
      functional genes in olive flounder. We identified single nucleotide polymorphisms
      (SNPs) from expressed sequence tag (EST) database in olive flounder; out of a
      total 4,327 ESTs, 693 contigs and 514 SNPs were detected in total EST, and these
      substitutions include 297 transitions and 217 transversions. As a result, 144 SNP
      markers were developed on the basis of 514 SNP to selection of useful gene
      region, and then applied to each of eight wild and culture olive flounder (total
      16 samples). In our experimental result, only 32 markers had detected
      polymorphism in sample, also identified 21 transitions and 11 transversions,
      whereas indel was not detected in polymorphic SNPs. Heterozygosity of wild and
      cultured olive flounder using the 32 SNP markers is 0.34 and 0.29, respectively.
      In conclusion, we identified SNP and polymorphism in olive flounder using newly
      designed marker, it supports that developed markers are suitable for SNP
      detection and diversity analysis in olive flounder. The outcome of this study can
      be basic data for researches for immunity gene and characteristic with SNP. 

PMID- 25949199
TI  - Genetic distances and variations of three clupeid species determined by PCR
      technique.
AB  - In this study, seven oligonucleotides primers were shown to generate the shared
      loci, specific loci, unique shared loci to each species and shared loci by the
      three species which could be obviously calculated. Euclidean genetic distances
      within- and between-species were also calculated by complete linkage method with
      the sustenance of the hierarchical dendevrepogram program Systat version 13. The
      genomic DNA isolated from herring (Clupea pallasii), Korean anchovy (Coilia
      nasus) and large-eyed herring (Harengula zunashi), respectively, in the Yellow
      Sea, were amplified several times by PCR reaction. The hierarchical
      dendevrepogram shows three chief branches: cluster 1 (PALLASII 01, 02, 03, 04, 06
      and 07), cluster 2 (NASUS 08, 09, 10, 11, 12, 13 and 14), and cluster 3 (ZUNASHI
      15, 16, 17, 18, 19, 20, 21 and PALLASII 05). In three clupeid species, the
      shortest genetic distance displaying significant molecular difference was between
      individual PALLASII no. 03 and PALLASII no. 02 (0.018). Individual no. 06 of
      PALLASII was most distantly related to NASUS no. 11 (genetic distance = 0.318).
      Individuals from herring (C. pallasii) species (0.920) exhibited higher
      bandsharing values than did individuals from Korean anchovy (C. nasus) species
      (0.872) (P<0.05). As a result, this PCR analysis generated on the genetic data
      displayed that the herring (C. pallasii) species was widely separated from Korean
      anchovy (C. nasus) species. Reversely, individuals of Korean anchovy (C. nasus)
      species were a little closely related to those of large-eyed herring (H. zunashi)
      species. 

PMID- 25949200
TI  - Expressional Modulation of Connexin Isoforms in the Initial Segment of Male Rat
      treated with Estradiol Benzoate or Flutamide.
AB  - Direct cell-cell communication through connexin (Cx) complexes is a way to
      achieve functional accordance of cells within a tissue or an organ. The initial
      segment (IS), a part of the epididymis, plays important roles in sperm
      maturation. Steroid hormones influence on expression of a number of genes in the
      IS of adult animals. However, developmental effect of sex hormones on the gene
      expression in the IS has not been examined. In this study, estradiol benzoate
      (EB, an estrogen agonist) or flutamide (Flu, an andevrepogen antagonist) was
      exogenously administrated at 1 week of postnatal age, and expressional changes of
      Cx genes in the IS were determined at 4 months of age by a quantitative real-time
      PCR analysis. Treatment of EB at 0.015 MUg/kg body weight (BW) increased
      expression of Cx30.3, 31.1, and 43 genes. However, treatment of 1.5 MUg EB/kg BW
      resulted in expressional decreases of Cx31, 32, and 45 genes and caused increases
      of Cx30.3 and 43 gene expression. Significant decreases of Cx31, 31.1, 32, 37,
      and 45 gene expression were detected with a treatment of 500 MUg Flu/kg BW, while
      expression of Cx43 gene was significantly increased with a treatment of 500 MUg
      Flu/kg BW. A treatment of 50 mg Flu/kg BW led to significant increases of Cx30.3,
      32, 37, 40, and 43 gene expression. These findings imply that exogenous exposure
      of steroidal hormones during the early developmental period would result in
      aberrant expression of Cx genes in the adult IS. 

PMID- 25949201
TI  - The Tissue Distribution of Nesfatin-1/NUCB2 in Mouse.
AB  - Nesfatin-1, an anorexic nucleobindin-2 (NUCB2)-derived hypothalamic peptide,
      controls appetite and energy metabolism. Recent studies show that nesfatin
      1/NUCB2 is expressed not only in the brain but also in gastric and adipose
      tissues. Thus, we investigated the distributions of nesfatin-1/NUCB2 in various
      tissues of male and female mice by real-time PCR, western blotting, and
      immunohistochemical staining. Real-time PCR analyses showed that NUCB2 mRNA was
      predominantly expressed in the pituitary and at lower levels in the hypothalamus,
      spleen, thymus, heart, liver, and muscle of both male and female mice. Expression
      was much higher in reproductive organs, such as the testis, epididymis, ovary,
      and uterus, than in the hypothalamus. Western blot analysis of the nesfatin-1
      protein level showed similar results to the real-time PCR analyses in both male
      and female mice. These results suggest that nesfatin-1/NUCB2 have widespread
      physiological effects in endocrine and non-endocrine organs. In addition,
      immunohistochemical staining revealed that nesfatin-1 was localized in
      interstitial cells, including Leydig cells and in the columnar epithelium of the
      epididymis. Nesfatin-1 was also expressed in theca cells and interstitial cells
      in the ovary and in epithelial cells of the endometrium and uterine glands in the
      uterus. These results suggest that nesfatin-1 is a novel potent regulator of
      steroidogenesis and gonadal function in male and female reproductive organs.
      Further studies are required to elucidate the functions of nesfatin-1 in various
      organs of male and female mice. 

PMID- 25949202
TI  - Morphological Development of Larvae and Juveniles of Acanthopagrus schlegeli.
AB  - Newly hatched black porgy larvae (Acanthopagrus schlegeli) swam to the surface,
      with the mouth and anus still closed and were 1.90-2.11 mm (mean, 2.0 mm) in
      total length (TL). The larvae were 2.71-2.94 mm TL (mean, 2.82 mm) on day 2 after
      hatching. At this time, about two-thirds of the yolk was absorbed, the bladder
      and intestines had formed, and the mouth and anus were open. Total length was
      4.32-4.66 mm (mean, 4.45 mm) at the post-larval stage on days 5-6 after hatching,
      and the yolk and oil globule were almost absorbed. The end of the notochord began
      to flex, and 6-8 caudal fin rays were visible. The larvae were 15.37-16.1 mm TL
      (mean, 15.83 mm) at the juvenile stage on days 30-32 after hatching, and the
      number of rays in all fins was completely revealed. 

PMID- 25949203
TI  - Oocyte Degeneration Associated with Follicle Cells in Female Mactra chinensis
      (Bivalvia: Mactridae).
AB  - Ultrastructural studies of oocyte degeneration in the oocyte, and the functions
      of follicle cells during oocyte degeneration are described to clarify the
      reproductive mechanism on oocyte degeneration of Mactra chinensis using
      cytological methods. Commonly, the follicle cells are attached to the oocyte.
      Follicle cells play an important role in oocyte degeneration. In particular, the
      functions of follicle cells during oocyte degeneration are associated with
      phagocytosis and the intracellular digestion of products. In this study,
      morphologically similar degenerated phagosomes (various lysosomes), which were
      observed in the degenerated oocytes, appeared in the follicle cells. After the
      spawning of the oocytes, the follicle cells were involved in oocyte degeneration
      through phagocytosis by phagolysosomes. Therefore, it can be assumed that
      follicle cells reabsorb phagosomes from degenerated oocytes. In this study, the
      presence of lipid granules, which occurred from degenerating yolk granules,
      gradually increased in degenerating oocytes. The function of follicle cells can
      accumulate reserves of lipid granules and glycogen in the cytoplasm, which can be
      employed by the vitellogenic oocyte. Based on observations of follicle cells
      attached to degenerating oocytes after spawning, the follicle cells of this
      species are involved in the lysosomal induction of oocyte degeneration for the
      reabsorption of phagosomes (phagolysosomes) in the cytoplasm for nutrient
      storage, as seen in other bivalves. 

PMID- 25949204
TI  - Seminiferous Epithelium Cycle in Bombina orientalis.
AB  - The purpose of the present study was to examine the seminiferous epithelium cycle
      of Bombina orientalis using a light microscope. The cycle was divided into a
      total of 10 stages, according to the morphological characteristics of the cells.
      The spermatogenetic cells included primary spermatogonia, secondary
      spermatogonia, primary spermatocytes, secondary spermatocytes, spermatid and
      sperm. At stage I, the primary spermatogonia was located closer to basal lamina
      of the seminiferous tubule without spermatocyst formations. Especially at the
      stage II, the secondary spermatogonia were located in the spermatocyst. The
      primary and secondary spermatocytes were found from stages III to VI. The
      secondary spermatocytes were smaller in size than the primary spermatocytes, but
      they had thicker nucleoplasm and smaller nuclei. The round-shaped, early sperm
      cells were formed in stage VII, and further divided at stage VIII to have more
      concentrated nucleoplasm before division to matured sperm cells. At stage X, the
      matured sperm cells emerged from the spermatocyst. Considering the above results,
      this study presented the special characteristics in the generation and type of
      sperm formation. The germ cell formation occurred in various stages, like the
      perspectives of Franca et al (1999), ultimately, providing taxonomically useful
      information. 

PMID- 25949205
TI  - Possible Involvement of Photoperiodic Regulation in Reproductive Endocrine System
      of Female Olive Flounder Paralichthys olivaceus.
AB  - This study investigated possible involvement of photoperiodic regulation in
      reproductive endocrine system of female olive flounder. To investigate the
      influence on brain-pituitary axis in endocrine system by regulating photoperiod,
      compared expression level of Kisspeptin and sbGnRH mRNA in brain and FSH-beta, LH
      beta and GH mRNA in pituitary before and after spawning. Photoperiod was treated
      natural photoperiod and long photoperiod (15L:9D) conditions from Aug. 2013 to
      Jun. 2014. Continuous long photoperiod treatment from Aug. (post-spawning phase)
      was inhibited gonadal development of female olive flounder. In natural
      photoperiod group, the Kiss2 expression level a significant declined in Mar.
      (spawning period). And also, FSH-beta, LH-beta and GH mRNA expression levels were
      increasing at this period. However, in long photoperiod group, hypothalamic
      Kiss2, FSH-beta, LH-beta and GH mRNA expression levels did not show any
      significant fluctuation. These results suggest that expression of hypothalamic
      Kiss2, GtH and GH in the pituitary would change in response to photoperiod and
      their possible involvement of photoperiodic regulation in reproductive endocrine
      system of the BPG axis. 

PMID- 25949207
TI  - Embryonic and Morphological Development of Larvae and Juvenile of the Buenos
      Aires Tetra, Hyphessobrycon anisitsi (Pisces Characidae) Characidae Fishes.
AB  - We have launched an investigation for Embryonic Development, Larvae and Juvenile
      Morphology, of Buenos aires tetra in order to build basic data of Characidae and
      fish seeding production. We brought 50 couples of Characidae from Bizidduck
      aquarium in Yeosu-si, Jeollanamdo, from Korea on March of 2015. We put them in
      the tetragonal glass aquarium (50*50*30 cm). Breeding water temperature was
      27.5~28.5 degrees C (mean 28.0+/-0.05 degrees C) and being maintained. The shape
      of fertilized egg was round shape, and it was adhesive demersal egg. The egg size
      was 0.63~0.91 mm (mean 0.74+/-0.07 mm, n=20). After getting fertilized egg, the
      developmental stage was gastrula stage, and embryo covered almost two-thirds of
      Yolk. Incubation was happened after 16 hours 13 minutes from gastrula stage, and
      the tail of juvenile came out first with tearing egg capsule. Immediately after
      the incubation, prelarvae had 3.78~3.88 mm length (mean 3.84+/-0.04 mm, n=5), and
      it had no mouth and anus yet. 34 days after hatching from the incubation,
      juvenile had 8.63~13.1 mm (mean 10.9+/-1.66 mm), and it had similar silver
      colored body shape with its mother. 

PMID- 25949206
TI  - Effects of Water Temperature Change on the Hematological Responses and Plasma
      Cortisol Levels in Growing of Red Spotted Grouper, Epinephelus akaara.
AB  - This study was conducted to determine the stress response [ethological (operculum
      movement number (OMN)), hematological (hematocrit and hemoglobin), biochemical
      (glucose, cortisol and glutamic oxaloacetic transaminase (GOT))] in red spotted
      grouper, Epinephelus akaara during exposure of different water temperature in
      winter season. This species (Total length, 18.56+/-0.34 cm) previously maintained
      in water temperature of 15 degrees C were transferred to 15, 20 and 25 degrees C.
      During experimental period (7 days), OMN, hematocrit (Ht), glucose and GOT values
      were significantly high in 15 degrees C when compared to 20 and 25 degrees C.
      Hemoglobin value was also increased at 15 degrees C, but no significant
      differences. There was no differences in cortisol levels among the temperature
      groups. No fish mortality was observed during the experimental period. From these
      results, 15 degrees C is likely more stressful to red spotted grouper than 20
      degrees C and 25 degrees C. These observations confirm that red spotted grouper
      adapts better to temperatures between 20 and 25 degrees C during the winter
      season. 

PMID- 25949208
TI  - Gonadal Development, Spawning and Plasma Sex Steroid Levels of the Indoor
      Cultured Grunt, Hapalogenys nitens.
AB  - The gonadosomatic index (GSI), gonadal development and changes in hormones in
      plasma level of the indoor cultured grunt (Hapalogenys nitens) were investigated
      by histological study from August 2011 to October 2012. The GSI showed similar
      trends with gonad developmental stages during the culture periods. Changes in
      plasma level of estradiol-17beta of female H. nitens reached the highest value
      before the spawning period, and seasonal changes in plasma level of estradiol
      17beta were similar in trends of oocyte developments and GSI changes.
      Testosterone levels of male H. nitens reached the highest value before and after
      the spent stage. Ovarian developmental stages of H. nitens could be classified
      into early growing stage, late growing stage, mature stage, ripe and spawning
      stage, recovery and resting stage. The testicular developmental stages could be
      divided into growing stage, mature stage, ripe and spent stage, and recovery and
      resting stage. 

PMID- 25949209
TI  - Exogenous exposure to estradiol benzoate or flutamide at the weaning age alters
      expression of connexin isoforms in the initial segment of male rat.
AB  - Connexin (Cx) is a complex which allows direct communication between neighboring
      cells via exchange of signaling molecules and eventually leads to functional
      harmony of cells in a tissue. The initial segment (IS) is an excurrent duct of
      male reproductive tract and expression of numerous genes in the IS are controlled
      by andevrepogens and estrogens. The effects of these steroid hormones on gene
      expression in the IS during postnatal development have not extensively examined.
      The present research investigated expressional modulation of Cx isoforms in the
      IS by exogenous exposure to estrogen agonist, estradiol benzoate (EB), or
      andevrepogen antagonist, flutamide (Flu), at weaning age. Two different doses of
      EB or Flu were subcutaneously administrated in 21-day old of male rats, and
      expressional changes of Cx isoforms in the adult IS were analyzed by quantitative
      real-time PCR. Treatment of a low-dose EB (0.015 MUg/kg body weight) resulted in
      an increased expression of Cx31 gene and a decreased expression of Cx37 gene. A
      high-dose EB (1.5 MUg/kg body weight) treatment caused an increase of Cx31 gene
      expression. Increased levels of Cx30.3 and Cx40 transcripts were observed with a
      low-dose Flu (500 MUg/kg body weight) treatment. Treatment of high-dose Flu (50
      mg/kg body weight) led to expressional increases of Cx30.3, 40, and 43 genes. Our
      previous and present findings suggest differential responsiveness on gene
      expression of Cx isoforms in the IS by andevrepogens and estrogens at different
      postnatal ages. 

PMID- 25949210
TI  - Temporal Aquaporin 11 Expression and Localization during Preimplantation Embryo
      Development.
AB  - Environmental conditions during early mammalian embryo development are critical
      and some adaptational phenomena are observed. However, the mechanisms underlying
      them remain largely masked. Previously, we reported that AQP5 expression is
      modified by the environmental condition without losing the developmental potency.
      In this study, AQP11 was examined instead. To compare expression pattern between
      in vivo and in vitro, we conducted quantitative RT-PCR and analyzed localization
      of the AQP11 by whole mount immunofluorescence. When the fertilized embryos were
      developed in the maternal tracts, the level of Aqp11 transcripts was decreased
      devrepamatically until 2-cell stage. Its level increased after 2-cell stage and
      peaked at 4-cell stage, but decreased again devrepamatically until morula stage.
      Its transcript level increased again at blastocyst stage. In contrast, the levels
      of Aqp11 transcript in embryos cultured in vitro were as follows. The patterns of
      expression were similar but the overall levels were low compared with those of
      embryos grown in the maternal tracts. AQP11 proteins were localized in
      submembrane cytoplasm of embryos collected from maternal reproductive tracts. The
      immune-reactive signals were detected in both trophectoderm and inner cell mass.
      However, its localization was altered in in vitro culture condition. It was
      localized mainly in the plasma membrane of the blastocysts contacting with
      external environment. The present study suggests that early stage embryo can
      develop successfully by themselves adapting to their environmental condition
      through modulation of the expression level and localization of specific genes
      like AQP11. 

PMID- 25949212
TI  - Geochemical evidence for the link between sulfate reduction, sulfide oxidation
      and phosphate accumulation in a Late Cretaceous upwelling system.
AB  - BACKGROUND: On Late Cretaceous Tethyan upwelling sediments from the
      Mishash/Ghareb Formation (Negev, Israel), bulk geochemical and biomarker analyses
      were performed to explain the high proportion of phosphates in the lower part and
      of organic matter (OM) preserved in upper parts of the studied section. The
      profile is composed of three facies types; the underlying Phosphate Member (PM),
      the Oil Shale Member (OSM) and the overlying Marl Member (MM). RESULTS: Total
      organic carbon (TOC) contents are highly variable over the whole profile reaching
      from 0.6% in the MM, to 24.5% in the OSM. Total iron (TFe) varies from 0.1% in
      the PM to 3.3% in the OSM. Total sulfur (TS) ranges between 0.1% in the MM and
      3.4% in the OSM, resulting in a high C/S ratio of 6.5 in the OSM section. A mean
      proportion of 11.5% total phosphorus (TP) in the PM changed abruptly with the
      facies to a mean value of only 0.9% in the OSM and the MM. The TOC/TOCOR ratios
      argue for a high bacterial sulfate reduction activity and in addition, results
      from fatty acid analyses indicate that the activity of sulfide-oxidizing activity
      of bacteria was high during deposition of the PM, while decreasing during the
      deposition of the OSM. CONCLUSIONS: The upwelling conditions effected a high
      primary productivity and consequently the presence of abundant OM. This, in
      combination with high sulfate availability in the sediments of the PM resulted in
      a higher sulfide production due to the activity of sulfate-reducing bacteria.
      Iron availability was a limiting factor during the deposition of the whole
      section, affecting the incorporation of S into OM. This resulted in the
      preservation of a substantial part of OM against microbial degradation due to
      naturally-occurring sulfurization processes expressed by the high C/S ratio of
      6.5 in the OSM. Further, the abundant sulfide in the pore water supported the
      growth of sulfide-oxidizing bacteria promoting the deposition of P, which
      amounted to as much as 15% in the PM. These conditions changed drastically from
      the PM to the OSM, resulting in a significant reduction of the apatite
      precipitation and a high concentration of reactive S species reacting with the
      OM.

PMID- 25949211
TI  - Cured of primary bone cancer, but at what cost: a qualitative study of functional
      impairment and lost opportunities.
AB  - Purpose. Our study aims to explore how former cancer patients experience physical
      and psychosocial late effects 3-7 years after they underwent treatment for
      primary bone sarcoma in the hip/pelvic region. A qualitative, phenomenological,
      and hermeneutic design was applied. Methods. Sarcoma survivors (n = 10)
      previously treated at Oslo University Hospital, Norwegian Radium Hospital were
      selected to participate. In-depth and semistructured interviews were conducted.
      The interviews were analysed using inductive thematic analysis. Results. The
      participants reported that the late effects had three core spheres of impact:
      "their current daily life," "their future opportunities," and "their identity."
      They expressed negative changes in activity, increased dependence on others, and
      exclusion from participation in different areas. Their daily life, work, sports
      activities, and social life were all affected. Several of their experiences are
      similar to those described by people with functional impairment or disability.
      Conclusion. Patients cured of bone cancer in the hip/pelvic region pay a
      significant price in terms of functional impairment, practical challenges,
      exclusion from important aspects of life, and loss of previous identity. It is
      important to appreciate this in order to help bone cancer survivors who struggle
      to reorient their life and build a secure new identity. 

PMID- 25949213
TI  - Mucus mediated protection against acute colitis in adiponectin deficient mice.
AB  - BACKGROUND: Acute ulcerative colitis is an inflammation-driven condition of the
      bowel. It hampers the general homeostasis of gut, resulting in decreased mucus
      production and epithelial cell renewal. Adiponectin (APN), an adipocytokine, is
      secreted by the adipose tissue and has been debated both as a pro-inflammatory or
      anti-inflammatory protein depending on the disease condition and
      microenvironment. The present study delineates the role of APN depletion in mucus
      modulation in a model of acute colitis. METHODS: APNKO and C57BL/6 (WT) male mice
      were given 2% DSS ad libidum for 5 days in drinking water, followed by normal
      drinking water for the next 5 days. Hematoxyline-eosin and Alcian Blue staining
      was used to observe the general colonic morphology and goblet cell quantification
      respectively. Protein expression levels were quantified by Western blot for
      MATH1, Hes1, MUC2 and MUC4. ELISA was used to study the levels of TNF-alpha, IL-6
      and IL-1beta. RESULTS: APNKO mice showed significantly higher goblet to
      epithelial cell ratios, lower pro-inflammatory cytokines and higher MUC2 levels
      as compared to the WT mice. The protein expression levels for the mucin MUC2
      supported the histopathological findings. An increase in colon tissue-secreted
      levels of pro-inflammatory with a reduction in anti-inflammatory cytokines in
      presence of APN support the pro-inflammatory role of APN during acute
      inflammation. CONCLUSION: Absence of APN is protective against DSS-induced acute
      colonic inflammation by means of reducing colon tissue-secreted pro-inflammatory
      cytokines, modulating goblet and epithelial cell expressions, and increasing the
      levels of secretory mucin MUC2.

PMID- 25949214
TI  - Comparative proteomics of Bt-transgenic and non-transgenic cotton leaves.
AB  - BACKGROUND: As the rapid growth of the commercialized acreage in genetically
      modified (GM) crops, the unintended effects of GM crops' biosafety assessment
      have been given much attention. To investigate whether transgenic events cause
      unintended effects, comparative proteomics of cotton leaves between the
      commercial transgenic Bt + CpTI cotton SGK321 (BT) clone and its non-transgenic
      parental counterpart SY321 wild type (WT) was performed. RESULTS: Using enzyme
      linked immunosorbent assay (ELISA), Cry1Ac toxin protein was detected in the BT
      leaves, while its content was only 0.31 pg/g. By 2-DE, 58 differentially
      expressed proteins (DEPs) were detected. Among them 35 were identified by MS.
      These identified DEPs were mainly involved in carbohydrate transport and
      metabolism, chaperones related to post-translational modification and energy
      production. Pathway analysis revealed that most of the DEPs were implicated in
      carbon fixation and photosynthesis, glyoxylate and dicarboxylate metabolism, and
      oxidative pentose phosphate pathway. Thirteen identified proteins were involved
      in protein-protein interaction. The protein interactions were mainly involved in
      photosynthesis and energy metabolite pathway. CONCLUSIONS: Our study demonstrated
      that exogenous DNA in a host cotton genome can affect the plant growth and
      photosynthesis. Although some unintended variations of proteins were found
      between BT and WT cotton, no toxic proteins or allergens were detected. This
      study verified genetically modified operation did not sharply alter cotton leaf
      proteome, and the target proteins were hardly checked by traditional proteomic
      analysis.

PMID- 25949215
TI  - Contact pathway of coagulation and inflammation.
AB  - The contact system, also named as plasma kallikrein-kinin system, consists of
      three serine proteinases: coagulation factors XII (FXII) and XI (FXI), and plasma
      prekallikrein (PK), and the nonenzymatic cofactor high molecular weight kininogen
      (HK). This system has been investigated actively for more than 50 years. The
      components of this system and their interactions have been elucidated from in
      vitro experiments, which indicates that this system is prothrombotic by
      activating intrinsic pathway, and proinflammatory by producing bioactive peptide
      bradykinin. Although the activation of the contact system have been implicated in
      various types of human disease, in only a few instances is its role clearly
      defined. In the last 10 years, our understanding of the contact system,
      particularly its biology and (patho)physiology has greatly increased through
      investigations using gene-modified animal models. In this review we will describe
      a revitalized view of the contact system as a critical (patho)physiologic
      mediator of coagulation and inflammation. 

PMID- 25949216
TI  - Cost-effectiveness of live oral attenuated human rotavirus vaccine in Tanzania.
AB  - BACKGROUND: Globally, diarrhoea is the second leading cause of morbidity and
      mortality, responsible for the annual loss of about 10% of the total global
      childhood disease burden. In Tanzania, Rotavirus infection is the major cause of
      severe diarrhoea and diarrhoeal mortality in children under five years.
      Immunisation can reduce the burden, and Tanzania added rotavirus vaccine to its
      national immunisation programme in January 2013. This study explores the cost
      effectiveness of introducing rotavirus vaccine within the Tanzania Expanded
      Programme on Immunisation (EPI). METHODS: We quantified all health system
      implementation costs, including programme costs, to calculate the cost
      effectiveness of adding rotavirus immunisation to EPI and the existing provision
      of diarrhoea treatment (oral rehydration salts and intravenous fluids) to
      children. We used ingredients and step down costing methods. Cost and coverage
      data were collected in 2012 at one urban and one rural district hospital and a
      health centre in Tanzania. We used Disability Adjusted Life Years (DALYs) as the
      outcome measure and estimated incremental costs and health outcomes using a
      Markov transition model with weekly cycles up to a five-year time horizon.
      RESULTS: The average unit cost per vaccine dose at 93% coverage is US$ 8.4, with
      marked difference between the urban facility US$ 5.2; and the rural facility US$
      9.8. RV1 vaccine added to current diarrhoea treatment is highly cost effective
      compared to diarrhoea treatment given alone, with incremental cost effectiveness
      ratio of US$ 112 per DALY averted, varying from US$ 80-218 in sensitivity
      analysis. The intervention approaches a 100% probability of being cost effective
      at a much lower level of willingness-to-pay than the US$609 per capita Tanzania
      gross domestic product (GDP). CONCLUSIONS: The combination of rotavirus
      immunisation with diarrhoea treatment is likely to be cost effective when
      willingness to pay for health is higher than USD 112 per DALY. Universal coverage
      of the vaccine will accelerate progress towards achievement of the child health
      Millennium Development Goals.

PMID- 25949217
TI  - Health care: the challenge to deal with uncertainty and value judgment.
AB  - The exponential increase of knowledge in the life sciences field, more
      specifically in health sciences, in the past few years has brought additional
      levels of complexity when deciding and implementing strategies in the health care
      system. A predominantly paternalistic way to decide about available options to
      maintain or improve individual or collective health has been moving to a shared
      decision model considering the empowered patient. In spite of the reduction of
      uncertainty when making health and health care decisions due to the advancement
      in scientific methods, and, in spite of the asymmetry of information, knowledge
      and power to make decisions, we are progressively recognizing the importance of
      individuals, the target of the intervention, to express their preferences and to
      take an active role in the decision making process. Health care stakeholders,
      recognizing the scarcity of resources available and the fortunate ever increasing
      amount of applicable knowledge and its corresponding interventions to improve the
      population quantity and quality of life, should stimulate society to address and
      discuss health care issues that will guide critical choices and define health
      care priorities based mostly on judgment and the best evidence available. 

PMID- 25949218
TI  - Breast cancer in young women in southern Tunisia: Anatomical study and clinical
      prognostic factors: About a series of 83 patients.
AB  - PURPOSE: To define epidemiological, clinical, therapeutic and prognostic factors
      influencing survival of breast cancer in young women younger than 35 in southern
      Tunisia. MATERIAL AND METHODS: This is a retrospective study of 83 patients
      younger than 35 years and treated within tumors mammary committee of Sfax.
      RESULTS: The mean age was 31.7 years. T2 stage, high grade with positive node
      tumors were frequent. Breast surgery was performed for 73 patients. Chemotherapy
      was neo-adjuvant, adjuvant and palliative for respectively 10, 62 and 13
      patients. Radiotherapy was delivered for 65 patients with curative intent and for
      8 metastatic patients. Endocrine therapy was adjuvant in 38 patients and
      palliative in 6 cases. The overall survival (OS) at 5 years was 66.8%. Pejorative
      prognostic factors in uni-variate analysis were clinical T stage (T3, T4), and
      the number of involved lymph nodes. CONCLUSION: Despite adequate treatment, the
      prognosis of breast cancer in young women remains worse. Early diagnosis is
      necessary to promote outcome.

PMID- 25949219
TI  - Medical physics in radiotherapy: The importance of preserving clinical
      responsibilities and expanding the profession's role in research, education, and
      quality control.
AB  - Medical physicists have long had an integral role in radiotherapy. In recent
      decades, medical physicists have slowly but surely stepped back from direct
      clinical responsibilities in planning radiotherapy treatments while medical
      dosimetrists have assumed more responsibility. In this article, I argue against
      this gradual withdrawal from routine therapy planning. It is essential that
      physicists be involved, at least to some extent, in treatment planning and
      clinical dosimetry for each and every patient; otherwise, physicists can no
      longer be considered clinical specialists. More importantly, this withdrawal
      could negatively impact treatment quality and patient safety. Medical physicists
      must have a sound understanding of human anatomy and physiology in order to be
      competent partners to radiation oncologists. In addition, they must possess a
      thorough knowledge of the physics of radiation as it interacts with body tissues,
      and also understand the limitations of the algorithms used in radiotherapy.
      Medical physicists should also take the lead in evaluating emerging challenges in
      quality and safety of radiotherapy. In this sense, the input of physicists in
      clinical audits and risk assessment is crucial. The way forward is to proactively
      take the necessary steps to maintain and advance our important role in clinical
      medicine. 

PMID- 25949220
TI  - Measurement and comparison of head scatter factor for 7 MV unflattened (FFF) and
      6 MV flattened photon beam using indigenously designed columnar mini phantom.
AB  - AIM: To measure and compare the head scatter factor for 7 MV unflattened and 6 MV
      flattened photon beam using a home-made designed mini phantom. BACKGROUND: The
      head scatter factor (Sc) is one of the important parameters for MU calculation.
      There are multiple factors that influence the Sc values, like accelerator head,
      flattening filter, primary and secondary collimators. MATERIALS AND METHODS: A
      columnar mini phantom was designed as recommended by AAPM Task Group 74 with high
      and low atomic number material for measurement of head scatter factors at 10 cm
      and d max dose water equivalent thickness. RESULTS: The Sc values measured with
      high-Z are higher than the low-Z mini phantoms observed for both 6MV-FB and 7MV
      UFB photon energies. Sc values of 7MV-UFB photon beams were smaller than those of
      the 6MV-FB photon beams (0.6-2.2% (Primus), 0.2-1.4% (Artiste) and 0.6-3.7%
      (Clinac iX (2300CD))) for field sizes ranging from 10 cm * 10 cm to 40 cm * 40
      cm. The SSD had no influence on head scatter for both flattened and unflattened
      beams. The presence of wedge filters influences the Sc values. The collimator
      exchange effects showed that the opening of the upper jaw increases Sc
      irrespective of FF and FFF. CONCLUSIONS: There were significant differences in Sc
      values measured for 6MV-FB and unflattened 7MV-UFB photon beams over the range of
      field sizes from 10 cm * 10 cm to 40 cm * 04 cm. Different results were obtained
      for measurements performed with low-Z and high-Z mini phantoms.

PMID- 25949221
TI  - Set-up uncertainty during postmastectomy radiotherapy with Segmented Photon Beams
      Technique.
AB  - AIM: To verify the reproducibility of patients irradiated after mastectomy on the
      immobilization system designed and manufactured for our hospital and to compare
      the Internal Protocol (IP) with the modified-No Action Level Protocol.
      BACKGROUND: Application of forward IMRT techniques requires a good
      reproducibility of patient positioning. To minimize the set-up error, an
      effective immobilization system is important. MATERIALS AND METHODS: The study
      was performed for two groups of 65 each. In the first group, portal images for
      anterior field were taken in 1-3 fractions and, subsequently, three times a week.
      In this group, the mNAL protocol was used. In the second group, the IP was used.
      The portal images from the anterior field and from the gantry 0 were taken during
      the 1-3 and 10 fractions. In both groups, image registration was performed off
      line. For each group the systematic and random errors and PTV margin were
      calculated. RESULTS: In the first group the value of the population systematic
      errors and random errors were 1.6 +/- 1.6 mm for the left-right, and 1.5 +/- 1.7
      mm for the cranial-caudal directions, respectively, 1.7 +/- 1.3 mm, and 1.9 +/-
      1.3 mm for the second group. The PTV margins for the left-right and cranial
      caudal directions were 5.1 and 4.9 mm for the first group and 5.4 and 6.4 mm for
      the second group. CONCLUSIONS: For patients immobilized with our support device
      treated according to the mNAL protocol or IP, a good set-up reproducibility was
      obtained. Implementation of IP limits the number of required images.

PMID- 25949222
TI  - Assessment and evaluation of MV image guidance system performance in
      radiotherapy.
AB  - BACKGROUND AND AIM: The clinical use of imaging system in image guided
      radiotherapy (IGRT) necessitates performing periodic quality assurance of the
      system to be confident in applying corrections for patient set-up errors. We aim
      to develop and implement a quality assurance (QA) programme for megavoltage (MV)
      based image guidance system and assess its long term performance for a period of
      3 years. MATERIALS AND METHODS: Periodic QA tests were performed for the MV
      planar and cone beam computed tomography (CBCT) imaging system to assess the
      system safety, mechanical and geometrical accuracy, image quality and dose. The
      tests were performed using the equipment supplied by the manufacturer along with
      the image guidance system and using simple methods developed in-house. The test
      results were compared with expected or baseline values established during
      commissioning. RESULTS: The safety system was found to be functional. The results
      of mechanical and geometrical tests were in good agreement with the expected
      results. The system mechanical positioning was stable and reproducible within +/
      2 mm accuracy. The image quality and the imaging dose of the planar and CBCT
      imaging were found to agree with the baseline values and the manufacturer
      specifications. DISCUSSION: Throughout the three-year period, all the QA tests
      were within the specification. The mechanical and geometrical tests are most
      crucial as they directly affect the patient positioning accuracy. CONCLUSION: We
      conclude that the MV image guidance system is efficient to perform IGRT and
      insist to perform periodic QA tests and calibration for the system.

PMID- 25949223
TI  - Dependence of the safe rectum dose on the CTV-PTV margin size and treatment
      technique.
AB  - BACKGROUND: Late rectal injury is a common side effect of external beam
      radiotherapy for prostate cancer. AIM: The aim of this study was to evaluate what
      total dose may be safely delivered for prostate patients for 3DCRT and IMRT
      techniques and the CTV-PTV margin. MATERIALS AND METHODS: 3DCRT and IMRT plans
      were prepared for 12 patients. For each patient PTV was defined with CTV-PTV
      margins of 0.4, 0.6, ..., 1.0 cm, and total doses of 70, 72, ..., 80 Gy, with 2
      Gy dose fraction. NTCP values for the rectum were calculated using the Lyman
      model. Both techniques were compared in terms of population mean DVH. RESULTS:
      Significantly smaller NTCPs for IMRT were obtained. For both techniques
      diminishing the margin CTV-PTV of 2 mm leads to decreasing the NTCP of about
      0.03. For total dose of 80 Gy the NTCP was smaller than 10% for the 4 mm margin
      only. The QUANTEC dose volume constraints were more frequently fulfilled for the
      IMRT technique than for the 3DCRT technique. CONCLUSIONS: The IMRT technique is
      safer for prostate patients than the 3DCRT. If very high total doses are applied
      the CTV-PTV margin of 0.4 cm and the IMRT technique should be used. If the CTV
      PTV margin of 0.6 cm is applied, the NTCP is smaller than 10% for the 3DCRT and
      IMRT techniques for the total doses smaller than 74 Gy and 78 Gy, respectively.

PMID- 25949224
TI  - A Monte Carlo study on dose distribution evaluation of Flexisource (192)Ir
      brachytherapy source.
AB  - AIM: The aim of this study is to evaluate the dose distribution of the
      Flexisource (192)Ir source. BACKGROUND: Dosimetric evaluation of brachytherapy
      sources is recommended by task group number 43 (TG. 43) of American Association
      of Physicists in Medicine (AAPM). MATERIALS AND METHODS: MCNPX code was used to
      simulate Flexisource (192)Ir source. Dose rate constant and radial dose function
      were obtained for water and soft tissue phantoms and compared with previous data
      on this source. Furthermore, dose rate along the transverse axis was obtained by
      simulation of the Flexisource and a point source and the obtained data were
      compared with those from Flexiplan treatment planning system (TPS). RESULTS: The
      values of dose rate constant obtained for water and soft tissue phantoms were
      equal to 1.108 and 1.106, respectively. The values of the radial dose function
      are listed in the form of tabulated data. The values of dose rate (cGy/s)
      obtained are shown in the form of tabulated data and figures. The maximum
      difference between TPS and Monte Carlo (MC) dose rate values was 11% in a water
      phantom at 6.0 cm from the source. CONCLUSION: Based on dosimetric parameter
      comparisons with values previously published, the accuracy of our simulation of
      Flexisource (192)Ir was verified. The results of dose rate constant and radial
      dose function in water and soft tissue phantoms were the same for Flexisource and
      point sources. For Flexisource (192)Ir source, the results of TPS calculations in
      a water phantom were in agreement with the simulations within the calculation
      uncertainties. Furthermore, the results from the TPS calculation for Flexisource
      and MC calculation for a point source were practically equal within the
      calculation uncertainties.

PMID- 25949225
TI  - Effectiveness of PET/CT with (18)F-fluorothymidine in the staging of patients
      with squamous cell head and neck carcinomas before radiotherapy.
AB  - AIM: The aim of our study was to compare the staging of the disease declared
      before anticancer treatment was begun with the staging that was found after the
      planning PET/CT scanning with (18)F-FLT was performed. BACKGROUND: PET/CT in
      radiotherapy planning of head and neck cancers can facilitate the contouring of
      the primary tumour and the definition of metastatic lymph nodes. MATERIALS AND
      METHODS: Between November 2010 and November 2013, 26 patients suffering from head
      and neck carcinomas underwent planning PET/CT examination with (18)F-FLT. We
      compared the staging of the disease and the treatment strategy declared before
      and after (18)F-FLT-PET/CT was performed. RESULTS: The findings from (18)FLT
      PET/CT led in 22 patients to a change of staging: in 19 patients it led to
      upstaging of the disease and in 3 patients it led to downstaging of the disease.
      In one patient, a secondary malignancy was found. CONCLUSIONS: We have confirmed
      in this study that the use of (18)F-FLT-PET/CT scanning in radiotherapy planning
      of squamous cell head and neck carcinomas has a great potential in the precise
      evaluation of disease staging and consequently in the precise determination of
      target volumes.

PMID- 25949226
TI  - Tailor-made treatment combined with proton beam therapy for children with
      genitourinary/pelvic rhabdomyosarcoma.
AB  - BACKGROUND: Rhabdomyosarcoma (RMS) is one of the most common soft tissue sarcomas
      among children. Patients who developed genitourinary/pelvic rhabdomyosarcoma
      (GU/P-RMS) have a higher complication ratio and relatively poorer event free
      survival, with local therapy being very important. While proton beam therapy
      (PBT) is expected to reduce co-morbidity, especially for children, this lacks
      firm evidence and analysis. We analyzed GU/P-RMS children who had undergone
      multimodal therapy combined with PBT at a single institution. METHOD: We
      retrospectively reviewed charts of children with GU/P-RMS treated from January
      2007 to May 2013 at the University of Tsukuba Hospital who had undergone
      multimodal therapy with PBT. RESULTS: There were 5 children and their median age
      at diagnosis was 2.8 years (0.6-4.4 years). Primary sites were the bladder (2)
      and the prostate (3). All received neo-adjuvant chemotherapy and 3 underwent
      chemotherapy during PBT (Group Cx). All patients of Group Cx developed
      leukocytopenia (WBC <1000/MUL). The median dose of PBT was 47.7 GyE (41.4-50.4
      GyE). All patients survived by their last hospital visit (median, 36 months).
      CONCLUSIONS: We analyzed multimodal treatment combined with PBT applied for GU/P
      RMS. PBT was well tolerated and could be a plausible choice instead of photon
      therapy for this population.

PMID- 25949227
TI  - Local experience in cervical cancer imaging: Comparison in tumour assessment
      between TRUS and MRI.
AB  - OBJECTIVE: The aim of study was to analyze the accuracy of TRUS (transrectal
      ultrasound) vs. MRI (magnetic resonance imaging) and clinical gynecological
      examination estimation in the evaluation of tumor dimensions. METHODS: The
      patients inclusion criterion included primarily pathologically squamous cell
      carcinoma, but excluded were patients who had not undergone BT (brachytherapy)
      and treated with palliative intent. We offer two types of treatment for locally
      advanced cervical cancer: (a) radiochemotherapy followed by surgery and (b)
      exclusive radiochemotherapy. Imaging tests follow the presence of tumor and tumor
      size (width and thickness). Each examination was performed by a different
      physician who had no knowledge of the others' findings. All patients underwent
      MRI prior to EBRT (external beam radiation therapy) while 18 of them also at the
      time of the first brachytherapy application. For the analysis we used the r
      Pearson correlation coefficient. RESULTS: In 2013, 26 patients with cervical
      cancer were included. A total of 44 gynecological examinations were performed, 44
      MRIs and 18 TRUSs. For the comparisons prior to EBRT the correlation coefficient
      between TRUS vs. MRI was r = 0.79 for AP and r = 0.83 for LL, for GYN vs. MRI was
      r = 0.6 for AP and r = 0.75 for LL. Prior to BT for GYN vs. MRI, r values were
      0.60 and 0.63 for AP and LL, respectively; for GYN vs. TRUS, r values were 0.56
      and 0.78 for AP and LL, respectively. CONCLUSIONS: A high correlation between the
      three examinations was obtained. As such, TRUS can be considered a suitable
      method in the evaluation of tumor dimensions.

PMID- 25949228
TI  - Fractionated stereotactic radiotherapy plus bevacizumab after response to
      bevacizumab plus irinotecan as a rescue treatment for high-grade gliomas.
AB  - AIM: To evaluate the possibility of implementing a new scheme of rescue treatment
      after relapse or progression of high-grade glioma (HGG) treated at the first-line
      with bevacizumab and irinotecan (BVZ+CPT11), evaluating the response and toxicity
      of associating BVZ and fractionated stereotactic radiotherapy (BVZ+FSRT).
      MATERIALS AND METHODS: We retrospectively analysed data from 59 patients with
      relapse of HGG. Nine patients with HGG relapse after treatment using the Stupp
      protocol that were treated with BVZ+CPT11 for progression between July 2007 and
      August 2012, after which the response was assessed according to the Revised
      Assessment in Neuro-Oncology (RANO) criteria. BVZ was administered at a dose of
      10 mg/kg and FSRT up to a prescribed dose of 30 Gy, 500 cGy per fraction, three
      days a week. The median follow-up was 38 months. RESULTS: The treatment was well
      tolerated by all patients. The response after nuclear magnetic resonance imaging
      (MRI) at 3-6 months was progression in two patients, stable disease in four, and
      three patients had a partial response. The median overall survival (OS) from
      diagnosis until death or the last control was 36.8 months. The median progression
      free survival (PFS) was 10.8 months. The results from tumour sub-group analysis
      indicated that the PFS was not statistically significant although it seemed that
      it was higher in grade-III. The OS was higher in grade-III gliomas. CONCLUSIONS:
      The combination of BVZ+FSRT as a second-line HGG relapse rescue treatment is well
      tolerated and seems to offer promising results. We believe that multi-centre
      prospective studies are needed to determine the long-term efficacy and toxicity
      of this therapeutic approach.

PMID- 25949229
TI  - Isolated jejunal metastasis in a patient with cervical cancer: A case report.
AB  - BACKGROUND: In approximately 8% of cervical carcinoma patients, gastrointestinal
      tract is involved, most commonly the rectosigmoid portion, because of local
      extension. Isolated metastases to small bowel are exceedingly rare. CASE REPORT:
      We present a case of a 63-year-old woman with cervical cancer who developed
      isolated jejunal metastasis 8 months after postoperative chemoradiotherapy. The
      patient was alive with no evidence of disease 6 months after resection of
      metastasis. Very few cases have been reported concerning squamous cell carcinoma
      of the cervix with documented metastases to the small bowel. There is only one
      published case report of cervical cancer with multiple metastases to the small
      intestine and jejunum. To our knowledge, this is the first case of cervical
      cancer with isolated jejunal metastasis, which was initially demonstrated with
      positron emission tomography and confirmed histopathologically. CONCLUSION:
      Although the exact mechanism underlying the isolated metastasis is unknown,
      hematogenous spread or tumor seeding during surgery may play a role.

PMID- 25949230
TI  - Delayed reconstruction of the upper digestive tract in a patient following total
      pharyngolaryngectomy with resection of the cervical oesophagus.
AB  - Carcinoma of the hypopharynx is an uncommon disease, with an annual incidence of
      approximately 1 in 100,000. Post-cricoid carcinoma is more common in women and is
      not usually associated with tobacco and alcohol abuse. Reconstruction of large
      pharyngeal defects following surgery for squamous cell carcinoma is complex and
      often requires microvascular free tissue transfer to achieve the best oncological
      and functional outcomes. The most common complications of such procedures include
      fistulas and strictures of the neopharynx. Here, we describe a case of a female
      patient admitted to the Head and Neck Department at our hospital to undergo
      delayed reconstruction following pharyngolaryngectomy and removal of the cervical
      oesophagus. Several complications occurred during post-operative care, including
      stricture and skin dehiscence. At present, the patient is able to swallow saliva
      and is currently being prepared to return to a normal diet. 

PMID- 25949231
TI  - Annual Board of Editors meeting in Prague: Current and future directions for
      RPOR.

PMID- 25949232
TI  - Pain Management in Long-Term Care Communities: A Quality Improvement Initiative.
AB  - Pain is underrecognized and undertreated in the long-term care (LTC) setting. To
      improve the management of pain for LTC residents, the authors implemented a
      quality improvement (QI) initiative at one LTC facility. They conducted a needs
      assessment to identify areas for improvement and designed a 2-hour educational
      workshop for facility staff and local clinicians. Participants were asked to
      complete a survey before and after the workshop, which showed significant
      improvement in their knowledge of pain management and confidence in their ability
      to recognize and manage residents' pain. To measure the effectiveness of the QI
      initiative, the authors performed a chart review at baseline and at 3 and 8
      months after the workshop and evaluated relevant indicators of adequate pain
      assessment and management. The post-workshop chart reviews showed significant
      improvement in how consistently employees documented pain characteristics (ie,
      location, intensity, duration) in resident charts and in their use of targeted
      pain assessments for residents with cognitive dysfunction. The proportion of
      charts that included a documented plan for pain assessment was high at baseline
      and remained stable throughout the study. Overall, the findings suggest a QI
      initiative is an effective way to improve pain care practices in the LTC setting.

PMID- 25949233
TI  - A nutrition and conditioning intervention for natural bodybuilding contest
      preparation: case study.
AB  - Bodybuilding competitions are becoming increasingly popular. Competitors are
      judged on their aesthetic appearance and usually exhibit a high level of
      muscularity and symmetry and low levels of body fat. Commonly used techniques to
      improve physique during the preparation phase before competitions include
      dehydration, periods of prolonged fasting, severe caloric restriction, excessive
      cardiovascular exercise and inappropriate use of diuretics and anabolic steroids.
      In contrast, this case study documents a structured nutrition and conditioning
      intervention followed by a 21 year-old amateur bodybuilding competitor to improve
      body composition, resting and exercise fat oxidation, and muscular strength that
      does not involve use of any of the above mentioned methods. Over a 14-week
      period, the Athlete was provided with a scientifically designed nutrition and
      conditioning plan that encouraged him to (i) consume a variety of foods; (ii) not
      neglect any macronutrient groups; (iii) exercise regularly but not excessively
      and; (iv) incorporate rest days into his conditioning regime. This strategy
      resulted in a body mass loss of 11.7 kg's, corresponding to a 6.7 kg reduction in
      fat mass and a 5.0 kg reduction in fat-free mass. Resting metabolic rate
      decreased from 1993 kcal/d to 1814 kcal/d, whereas resting fat oxidation
      increased from 0.04 g/min to 0.06 g/min. His capacity to oxidize fat during
      exercise increased more than two-fold from 0.24 g/min to 0.59 g/min, while there
      was a near 3-fold increase in the corresponding exercise intensity that elicited
      the maximal rate of fat oxidation; 21% VO2max to 60% VO2max. Hamstring concentric
      peak torque decreased (1.7 to 1.5 Nm/kg), whereas hamstring eccentric (2.0 Nm/kg
      to 2.9 Nm/kg), quadriceps concentric (3.4 Nm/kg to 3.7 Nm/kg) and quadriceps
      eccentric (4.9 Nm/kg to 5.7 Nm/kg) peak torque all increased. Psychological mood
      state (BRUMS scale) was not negatively influenced by the intervention and all
      values relating to the Athlete's mood-state remained below average over the
      course of study. This intervention shows that a structured and scientifically
      supported nutrition strategy can be implemented to improve parameters relevant to
      bodybuilding competition and importantly the health of competitors, therefore
      questioning the conventional practices of bodybuilding preparation.

PMID- 25949235
TI  - Recovering 3D Shape with Absolute Size from Endoscope Images Using RBF Neural
      Network.
AB  - Medical diagnosis judges the status of polyp from the size and the 3D shape of
      the polyp from its medical endoscope image. However the medical doctor judges the
      status empirically from the endoscope image and more accurate 3D shape recovery
      from its 2D image has been demanded to support this judgment. As a method to
      recover 3D shape with high speed, VBW (Vogel-Breubeta-Weickert) model is proposed
      to recover 3D shape under the condition of point light source illumination and
      perspective projection. However, VBW model recovers the relative shape but there
      is a problem that the shape cannot be recovered with the exact size. Here, shape
      modification is introduced to recover the exact shape with modification from that
      with VBW model. RBF-NN is introduced for the mapping between input and output.
      Input is given as the output of gradient parameters of VBW model for the
      generated sphere. Output is given as the true gradient parameters of true values
      of the generated sphere. Learning mapping with NN can modify the gradient and the
      depth can be recovered according to the modified gradient parameters. Performance
      of the proposed approach is confirmed via computer simulation and real
      experiment. 

PMID- 25949234
TI  - Identification of chemical modulators of the constitutive activated receptor
      (CAR) in a gene expression compendium.
AB  - The nuclear receptor family member constitutive activated receptor (CAR) is
      activated by structurally diverse drugs and environmentally-relevant chemicals
      leading to transcriptional regulation of genes involved in xenobiotic metabolism
      and transport. Chronic activation of CAR increases liver cancer incidence in
      rodents, whereas suppression of CAR can lead to steatosis and insulin
      insensitivity. Here, analytical methods were developed to screen for chemical
      treatments in a gene expression compendium that lead to alteration of CAR
      activity. A gene expression biomarker signature of 83 CAR-dependent genes was
      identified using microarray profiles from the livers of wild-type and CAR-null
      mice after exposure to three structurally-diverse CAR activators (CITCO,
      phenobarbital, TCPOBOP). A rank-based algorithm (Running Fisher's algorithm (p
      value <= 10(-4))) was used to evaluate the similarity between the CAR biomarker
      signature and a test set of 28 and 32 comparisons positive or negative,
      respectively, for CAR activation; the test resulted in a balanced accuracy of
      97%. The biomarker signature was used to identify chemicals that activate or
      suppress CAR in an annotated mouse liver/primary hepatocyte gene expression
      database of ~1850 comparisons. CAR was activated by 1) activators of the aryl
      hydrocarbon receptor (AhR) in wild-type but not AhR-null mice, 2) pregnane X
      receptor (PXR) activators in wild-type and to lesser extents in PXR-null mice,
      and 3) activators of PPARalpha in wild-type and PPARalpha-null mice. CAR was
      consistently activated by five conazole fungicides and four perfluorinated
      compounds. Comparison of effects in wild-type and CAR-null mice showed that the
      fungicide propiconazole increased liver weight and hepatocyte proliferation in a
      CAR-dependent manner, whereas the perfluorinated compound perfluorooctanoic acid
      (PFOA) increased these endpoints in a CAR-independent manner. A number of
      compounds suppressed CAR coincident with increases in markers of inflammation
      including acetaminophen, concanavalin A, lipopolysaccharide, and 300 nm silica
      particles. In conclusion, we have shown that a CAR biomarker signature coupled
      with a rank-based similarity method accurately predicts CAR activation. This
      analytical approach, when applied to a gene expression compendium, increased the
      universe of known chemicals that directly or indirectly activate CAR,
      highlighting the promiscuous nature of CAR activation and signaling through
      activation of other xenobiotic-activated receptors. 

PMID- 25949236
TI  - The efficacy of endoscopic papillary balloon dilation for patients with acute
      biliary pancreatitis.
AB  - Background. No study investigated the efficacy and safety of endoscopic papillary
      balloon dilation (EPBD) for the treatment of acute biliary pancreatitis (ABP).
      Method. We retrospectively reviewed the effects of EPBD on patients with ABP from
      February 2003 to December 2012. The general data, findings of image studies,
      details of the procedure, and outcomes after EPBD were analyzed. Result. Total
      183 patients (male/female: 110/73) were enrolled. The mean age was 65.9 years.
      Among them, 155 patients had mild pancreatitis. The meantime from admission to
      EPBD was 3.3 days. Cholangiogram revealed filling defects inside the common bile
      duct (CBD) in 149 patients. The mean dilating balloon size was 10.5 mm and mean
      duration of the dilating procedure was 4.3 minutes. Overall, 124 patients had
      gross stones retrieved from CBD. Four (2.2%) adverse events and 2 (1.1%)
      intraprocedure bleeding incidents but no procedure-related mortality were noted.
      Bilirubin and amylase levels significantly decreased after EPBD. On average,
      patients resumed oral intake within 1.4 days. The clinical parameters and
      outcomes were similar in patients with different severity of pancreatitis.
      Conclusion. EPBD can be effective and safe for the treatment of ABP, even in
      patients presenting with severe disease. 

PMID- 25949238
TI  - Pandanus odoratissimus (Kewda): A Review on Ethnopharmacology, Phytochemistry,
      and Nutritional Aspects.
AB  - Pandanus odoratissimus Linn. (family: Pandanaceae) is traditionally recommended
      by the Indian Ayurvedic medicines for treatment of headache, rheumatism, spasm,
      cold/flu, epilepsy, wounds, boils, scabies, leucoderma, ulcers, colic, hepatitis,
      smallpox, leprosy, syphilis, and cancer and as a cardiotonic, antioxidant,
      dysuric, and aphrodisiac. It contains phytochemicals, namely, lignans and
      isoflavones, coumestrol, alkaloids, steroids, carbohydrates, phenolic compounds,
      glycosides, proteins, amino acids as well as vitamins and nutrients, and so
      forth. It is having immense importance in nutrition. A 100 g edible Pandanus
      pericarp is mainly comprised of water and carbohydrates (80 and 17 g, resp.) and
      protein (1.3 mg), fat (0.7 mg), and fiber (3.5 g). Pandanus fruits paste provides
      321 kilocalories, protein (2.2 g), calcium (134 mg), phosphorus (108 mg), iron
      (5.7 mg), thiamin (0.04 mg), vitamin C (5 mg), and beta-carotene (19 to 19,000
      MUg) (a carotenoid that is a precursor to vitamin A). Pandanus fruit is an
      important source of vitamins C, B1, B2, B3, and so forth, usually prepared as a
      Pandanus floured drink. Traditional claims were scientifically evaluated by the
      various authors and the phytochemical profile of plant parts was well
      established. The methods for analytical estimations were developed. However,
      there is paucity of systematic compilation of scientifically important
      information about this plant. In the present review we have systematically
      reviewed and compiled information of pharmacognostic, ethnopharmacology,
      phytochemistry, pharmacology, nutritional aspects, and analytical methods. This
      review will enrich knowledge leading the way into the discovery of new
      therapeutic agents with improved and intriguing pharmacological properties. 

PMID- 25949237
TI  - The anti-inflammatory activity of a novel fused-cyclopentenone phosphonate and
      its potential in the local treatment of experimental colitis.
AB  - A novel fused-cyclopentenone phosphonate compound, namely, diethyl 3-nonyl-5-oxo
      3,5,6,6a-tetrahydro-1H-cyclopenta[c]furan-4-ylphosphonate (P-5), was prepared and
      tested in vitro (LPS-activated macrophages) for its cytotoxicity and anti
      inflammatory activity and in vivo (DNBS induced rat model) for its potential to
      ameliorate induced colitis. Specifically, the competence of P-5 to reduce
      TNFalpha, IL-6, INFgamma, MCP-1, IL-1alpha, MIP-1alpha, and RANTES in LPS
      activated macrophages was measured. Experimental colitis was quantified in the
      rat model, macroscopically and by measuring the activity of tissue MPO and iNOS
      and levels of TNFalpha and IL-1beta. It was found that P-5 decreased the levels
      of TNFalpha and the tested proinflammatory cytokines and chemokines in LPS
      activated macrophages. In the colitis-induced rat model, P-5 was effective
      locally in reducing mucosal inflammation. This activity was equal to the activity
      of local treatment with 5-aminosalicylic acid. It is speculated that P-5 may be
      used for the local treatment of IBD (e.g., with the aid of colon-specific drug
      platforms). Its mode of action involves inhibition of the phosphorylation of MAPK
      ERK but not of p38 and had no effect on IkappaBalpha. 

PMID- 25949239
TI  - Determinants of Secondary Hyperparathyroidism in Bariatric Patients after Roux-en
      Y Gastric Bypass or Sleeve Gastrectomy: A Pilot Study.
AB  - Objective. Nutritional deficiencies are common after bariatric surgery. We aimed
      to assess the prevalence and possible predictors of secondary hyperparathyroidism
      (SHPT) in bariatric patients. Methods. A total of 95 patients who had undergone
      Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) were assessed after a
      median of 3 years after surgery. Anthropometric/demographic and weight-loss
      parameters were compared according to the presence of SHPT, independently for
      men/premenopausal women and postmenopausal women. Results. SHPT was highly
      prevalent (men/premenopausal women, 52.1%; postmenopausal women, 31.9%). Among
      men/premenopausal women, multivariate analysis indicated that SHPT was predicted
      by (a) 25-hydroxyvitamin D levels (Exp(B) = 0.869, P-value = 0.037),
      independently of age, sex, smoking; (b) calcium (Exp(B) = 0.159, P-value = 0.033)
      and smoking, independently of age and sex; (c) magnesium (Exp(B) = 0.026, P-value
      = 0.046) and smoking, independently of age and sex. Among postmenopausal women,
      SHPT was predicted by menopausal age independently of age, smoking, and levels of
      25-hydroxyvitamin D or calcium. The development of SHPT was not associated with
      the type of surgery. Conclusions. RYGB and SG exhibited similar effects regarding
      the regulation of the hypothalamus-pituitary-parathyroid axis after surgery.
      Vitamin D status and menopausal age appear to determine SHPT on the long term.
      SHPT should be sought and vigorously treated with calcium and vitamin D
      supplementation. 

PMID- 25949240
TI  - Effects of Storage Temperature and Time on Stability of Serum Tacrolimus and
      Cyclosporine A Levels in Whole Blood by LC-MS/MS.
AB  - Tacrolimus and cyclosporine A are immunosuppressant drugs with narrow therapeutic
      windows. The aim of this study was to investigate the stability of tacrolimus and
      cyclosporin A levels in whole blood samples under different storage conditions.
      Whole blood samples were obtained from 15 patients receiving tacrolimus and 15
      patients receiving cyclosporine A. Samples were immediately analyzed and then
      stored at different conditions (room temperature (24 degrees C-26 degrees C) for
      24 hours, +4 degrees C for 24 and 48 hours, and -20 degrees C for one month) and
      then analyzed again. For tacrolimus, there was a significant difference between
      samples analyzed immediately and those kept 24 hours at room temperature (P =
      0.005) (percent change 32.89%). However, there were no significant differences
      between the other groups. For cyclosporine A, there was a significant difference
      between samples analyzed immediately and those kept 24 hours (P = 0.003) (percent
      change 19.47%) and 48 hours (P = 0.002) (percent change 15.38%) at +4 degrees C
      and those kept 24 hours at room temperature (P = 0.011) (percent change 9.71%).
      Samples of tacrolimus should be analyzed immediately or stored at either +4
      degrees C or -20 degrees C, while samples of cyclosporine A should be analyzed
      immediately or stored at -20 degrees C. 

PMID- 25949241
TI  - Topical and intranasal analgesic therapy in a woman with refractory postherpetic
      neuralgia.
AB  - A patient-specific, stepped approach to topical and intranasal analgesic
      pharmacotherapy was effective in reducing refractory postherpetic neuralgia (PHN)
      not responding to the current standard of care for PHN. The use of topical
      analgesic therapy allowed for higher concentrations of medication locally while
      reducing the likelihood of systemic side effects common to the drugs used. No
      adverse effects were noted for either topical or intranasal drug therapy. The
      patient-specific, stepped approach resulted in clinically significant decreases
      in pain on visual analog scale (VAS), with the use of intranasal ketamine 10%
      solution and topical gabapentin 6%, ketoprofen 10%, lidocaine 5%, and ketamine
      10% cream. 

PMID- 25949242
TI  - Rho/MRTF-A-Induced Integrin Expression Regulates Angiogenesis in Differentiated
      Multipotent Mesenchymal Stem Cells.
AB  - Mesenchymal stem cells (MSCs) are known to undergo endothelial differentiation in
      response to treatment with vascular endothelial growth factor (VEGF), but their
      angiogenic ability is poorly characterized. In the present study, we aimed to
      further investigate the role of Rho/MRTF-A in angiogenesis by MSCs and the effect
      of the Rho/MRTF-A pathway on the expression of integrins alpha1beta1 and
      alpha5beta1, which are known to mediate physiological and pathological
      angiogenesis. Our results showed that increased expression of alpha1, alpha5, and
      beta1 was observed during angiogenesis of differentiated MSCs, and the Rho/MRTF-A
      signaling pathway was demonstrated to be involved in regulating the expression of
      integrins alpha1, alpha5, and beta1. Luciferase reporter assay and ChIP assay
      determined that MRTF-A could bind to and transactivate the integrin alpha1 and
      alpha5 promoters. Treatment with the Rho inhibitor C3 transferase, the Rho
      associated protein kinase (ROCK) inhibitor Y27632 or with shMRTF-A inhibited both
      the upregulation of alpha1, alpha5, and beta1 as well as angiogenesis.
      Furthermore, in human umbilical vein endothelial cells (HUVECs), MRTF-A deletion
      led to marked reductions in cell migration and vessel network formation compared
      with the control. These data demonstrate that Rho/MRTF-A signaling is an
      important mediator that controls integrin gene expression during MSC-mediated
      angiogenic processes. 

PMID- 25949243
TI  - Investigation of competencies of nurses in disaster response by utilizing
      objective structured clinical examination.
AB  - BACKGROUND: Nurses are members of the health care team for crisis response.
      Identifying nurses' capability in responding to a disaster and promoting their
      preparedness will lead to effective use of human resources and decreasing the
      detrimental effects of disaster. The purpose of this article was to determine
      emergency nurses' competences in triage, life support, and basic clinical skills
      in disaster response. MATERIALS AND METHODS: This study was a descriptive study
      in which 40 emergency nurses were recruited by purposeful sampling. Moreover,
      their competencies in performing triage, life support, and basic clinical skills
      were evaluated by utilizing eight-station objective structured clinical
      examination (OSCE). RESULTS: Our findings showed that the mean scores of nurses'
      performance were: In triage (4.3 +/- 1.27), life support (4 +/- 1.5), airway
      management (5.3 +/- 1.7), chest tube insertion (7.3 +/- 1.8), nasogastric tube
      insertion (5.6 +/- 2.5), IV therapy (2.5 +/- 0.8), IV line insertion (6 +/- 1.4),
      suturing (9.1 +/- 1.6), and urinary catheterization (10.4 +/- 2.2). No
      statistically significant correlation was found between demographic variables and
      nurses' performance (P > 0.05). CONCLUSION: According to our findings, it can be
      concluded that competencies of nurses in performing triage, life support, and
      basic clinical skills were undesirable. Because emergency nurses are members of
      the emergency medical team, they should be prepared for disaster response via
      continuous training programs.

PMID- 25949244
TI  - Compliance with treatment regimen in women with gestational diabetes: Living with
      fear.
AB  - BACKGROUND: Gestational diabetes mellitus is a prevalent pregnancy complication
      that seriously endangers mothers' and babies' health. The aim of this study was
      to explore factors affecting treatment compliance among women with gestational
      diabetes mellitus. MATERIALS AND METHODS: A qualitative content analysis approach
      was employed. Twenty-five semi-structured interviews were conducted with
      hospitalized pregnant women with gestational diabetes mellitus. The research was
      conducted in four teaching hospitals in Tehran, Iran; purposive sampling was
      used. RESULTS: Participants' experiences regarding factors that influence
      treatment compliance fell into six categories: Unexpected diagnosis, the need for
      urgent change, temptation to consume inappropriate foods, life in the shadow of
      the illness, risk avoidance, and seeking adjustment. CONCLUSIONS: Holistic
      education of families on gestational diabetes, training specialist diabetes
      nurses, and referral to public health centers and diabetes clinics could increase
      treatment compliance. These findings could serve patients and the healthcare
      system in general, if considered by healthcare officials and policy makers.
      Furthermore, providing outpatient services, considering cultural dietary
      conventions when recommending diets, and alleviating the stigma associated with
      diabetes through mass media could also promote treatment compliance.

PMID- 25949246
TI  - Improving students' knowledge and attitude with regard to HIV.

PMID- 25949245
TI  - Iranian Kurdish women's experiences of childbirth: A qualitative study.
AB  - BACKGROUND: The experience of labor and birth, referred to as childbirth, is
      complex, multidimensional, and subjective, relating to both the outcome and the
      process that is experienced by an individual woman. The aim of this study was to
      describe the experience of childbirth among Kurdish women giving birth at Besat
      Hospital in Sanandaj, Iran. MATERIALS AND METHODS: A qualitative study was
      conducted using phenomenological approach. Women eligible for the study were
      recruited from the postpartum ward. Inclusion criteria were being an Iranian
      Kurdish woman, being nulliparous, and having vaginal childbirth. Data collection
      was performed between 2010 and 2011. Women were interviewed by the first
      researcher 6-12 weeks after they had given birth to their first child. RESULTS:
      All participants had spontaneous vaginal births without their husbands present.
      None of them received any analgesia or anesthesia during labor and birth. The
      findings are described under the following four themes: Feeling empowered,
      changing life, importance of being supported during labor, and the spiritual
      dimensions of giving birth. CONCLUSIONS: Women communicate through telling
      stories and create meaning as they articulate their feelings about pivotal life
      events such as childbirth. The findings of this study provide a useful first step
      toward the identification of aspects of Kurdish women's experience of giving
      birth. The women in this study identified that the presence or absence of
      effective support had a significant effect on their experience of labor and
      birth. It is important for midwives and other professionals to understand the
      benefits of support given for women during childbirth.

PMID- 25949247
TI  - Professional support as a facilitator to the development of Iranian nurses'
      clinical judgment: A content analysis.
AB  - BACKGROUND: Nurses' clinical judgment development is essential for the
      professional nursing practice. The aim of this study was to explore the
      facilitators to the development of Iranian nurses' clinical judgment. MATERIALS
      AND METHODS: A qualitative design using conventional content analysis method was
      employed in the study. A purposive sample of 24 participants was recruited from
      three hospitals located at Sanandaj, Iran. Study data were collected in 2013 by
      using semi-structured individual interviews. A content analysis approach was used
      to analyze the study data and MAXQDA was used for coding and categorizing the
      data. RESULTS: The main theme of the study was "professional support as a
      facilitator to the development of nurse's clinical judgment." The sub-themes of
      this main theme included "provision of direct support to nurses" and "provision
      of clinical judgment resources." The first sub-theme consisted of different types
      of managerial, clinical, educational, and social supports. The two categories of
      the second sub-theme included the provision of necessary clinical evidence and
      the provision of medical equipments. CONCLUSION: The study findings highlighted
      the importance of providing nurses with adequate professional support for
      facilitating the development of their clinical judgment.

PMID- 25949248
TI  - Spousal communication on family planning and perceived social support for
      contraceptive practices in a sample of Malaysian women.
AB  - BACKGROUND: In Malaysia, contraceptive prevalence rate (CPR) during past three
      decades has been steady, with only 34% of women practicing modern contraception.
      The aim of this study was to determine the factors associated with modern
      contraceptive practices with a focus on spousal communication and perceived
      social support among married women working in the university. MATERIALS AND
      METHODS: A cross-sectional study was carried out using self-administered
      structured questionnaire. The association between variables were assessed using
      Chi-square test, independent sample t-test, and logistic regression. RESULTS:
      Overall, 36.8% of women used modern contraceptive methods. Significant
      association was found between contraceptive practice and ethnicity (P = 0.003),
      number of pregnancies (P < 0.001), having child (P = 0.003), number of children
      (P < 0.001), positive history of mistimed pregnancy (P = 0.006), and experience
      of unwanted pregnancy (P = 0.003). The final model showed Malay women were 92%
      less likely to use modern contraception as compared to non-Malay women. Women who
      discussed about family planning with their spouses were more likely to practice
      modern contraception than the women who did not [odds ratio (OR): 2.2, Confidence
      Interval (CI): 1.3-3.7]. Those women with moderate (OR: 4.9, CI: 1.6-10.8) and
      strong (OR: 14, CI: 4.5-26.4) perception of social support for contraceptive
      usage were more likely to use modern contraception than the women with poor
      perception of social support. CONCLUSION: Spousal communication regarding family
      planning would be an effective way to motivate men for supporting and using
      contraceptives. Family planning education initiatives should target both men and
      women, particularly high-risk cases, for promoting healthy timing and spacing of
      pregnancies. Ethnic disparities need to be considered in planning reproductive
      health programs.

PMID- 25949249
TI  - Cultural perceptions and preferences of Iranian women regarding cesarean
      delivery.
AB  - BACKGROUND: Data was reported in Iran in 2013 has shown that almost 42 percent of
      deliveries in public hospitals and 90 percent in private hospitals were carried
      out with cesarean section. This high rate of cesarean requires careful
      consideration. It seems that making decision for cesarean is done under the
      influence of cultural perceptions and beliefs. So, this study was conducted to
      explore pregnant women's preferences and perceptions regarding cesarean delivery.
      MATERIALS AND METHODS: A focused ethnographic study was used. 12 pregnant women
      and 10 delivered women, seven midwives, seven gynecologist and nine non-pregnant
      women referred to the health clinics of Tonekabon, who selected purposively, were
      included in the study. To collect data semi-structured in-depth interviews and
      participant observation were used. Study rigor was confirmed through prolonged
      engagement, member check, expert debriefing, and thick description of the data.
      Data were analysed using thematic analysis and MAXQDA software. RESULTS: Four
      themes emerged from the data including personal beliefs, fear of vaginal
      delivery, cultural norms and values and also social network. These concepts
      played main roles in how women develop meanings toward caesarean, which affected
      their perceptions and preferences in relation to caesarean delivery. CONCLUSION:
      Most of pregnant women believed that fear of vaginal delivery is a major factor
      to choose caesarean delivery. Hence, midwives and physicians could help them
      through improving the quality of prenatal care and giving them positive
      perception towards vaginal delivery through presenting useful information about
      the nature of different modes of delivery, and their advantages and
      disadvantages, as well as the alternative ways to control labor pain.

PMID- 25949250
TI  - Decision-making for vaginal delivery in the North of Iran: A focused ethnography.
AB  - BACKGROUND: Many factors have been mentioned to influence decision-making for
      different kinds of delivery. Decision-making for vaginal delivery is under the
      influence of culture, perceptions, beliefs, values, attitudes, personalities, and
      knowledge. The current study aims at exploring the determinants of decision
      making for vaginal delivery in the north of Iran from women's perspective.
      MATERIALS AND METHODS: A focused ethnographic method with purposeful sampling
      method has been used. Semi-structured interviews and observation were conducted
      with 12 pregnant women and 10 delivered women, 7 midwives, 7 gynecologists, and 9
      non-pregnant women in Tonekabon clinics. Interviews and observations were
      recorded and transcribed. The accuracy of the extracted codes and themes was
      confirmed by restoration of the arranged and coded texts to the participants
      (member check) and by an expert person from outside the study context. Data were
      analyzed using thematic analysis and MAXqda software. RESULTS: Five themes were
      extracted from the data: Economic influencing factors, Cultural values and norms
      related to normal childbirth, Positive attitudes towards vaginal delivery, Role
      of important others, and Facilitators of natural birth. Several sub-themes and
      sub-sub themes also emerged from the data (e.g. safe delivery, forming maternal
      feelings, painful but tolerable, maternal role facilitator, inexpensive delivery,
      a process with good outcome and less complications, relief messenger).
      CONCLUSIONS: Giving enough information about vaginal delivery for pregnant women
      and their family members, training pregnant women to increase tolerance during
      labor pain, and modifying expenses can increase economic affordability, positive
      cultural norms and attitudes about vaginal delivery, proper social support, use
      of normal delivery facilitators, and direct them toward vaginal delivery.

PMID- 25949251
TI  - Predictors of mental health during pregnancy.
AB  - BACKGROUND: Pregnancy with anxious or depressive symptoms might be associated
      with worse birth outcomes. The aim of this study was to determine the demographic
      predictors of anxiety and depression symptoms in pregnant women. MATERIALS AND
      METHODS: We assessed pregnancy anxiety and depression levels among 142 women in
      three trimesters. All subjects completed two questionnaires: Demographic scale
      and the 21-item Depression Anxiety Stress Scale (DASS-21) questionnaire. Chi
      square test and regression analysis were used to assess the association between
      anxiety and depression symptoms with maternal age, maternal education, family
      income, gestational age, body mass index, parity, and pregnancy risk. RESULTS:
      25.3% of the pregnant women reported having depressive symptoms. Also, 49.3% of
      the subjects reported having anxiety symptoms. There was positive correlation
      between body mass index, gestational age, and pregnancy risk with depression
      symptom. Also, there was negative correlation between family income and maternal
      education level with anxiety symptom. In linear regression model, the variables
      of maternal age, maternal education, parity, abortion, gestational age, family
      income, body mass index, and pregnancy risk predicted 44.7% anxiety (F = 1.903, P
      = 0.006) and 68.1% depression (F = 2.101, P = 0.003). The strongest predictors of
      depression in pregnant women were pregnancy risk (beta = 0.361, P = 0.001) and
      maternal education (beta = -0.297, P = 0.006). Also, pregnancy risk (beta =
      0.523, P = 0.001) and gestational age (beta = 0.477, P = 0.01) were the important
      predictors of maternal anxiety in the pregnancy period. CONCLUSIONS: Pregnancy
      risk, gestational age, and education level are the strongest predictors of mental
      health in the pregnancy period. This result suggests that psychological support
      is needed for pregnant women with high risk and low education, especially in the
      third trimester, to improve their mental health.

PMID- 25949252
TI  - Body image and its relationship with sexual function and marital adjustment in
      infertile women.
AB  - BACKGROUND: Body image is related to cognitive, emotional, and physical aspects
      of women's life. Therefore, it is expected to have an important role in women's
      sexual health and marital adjustment too. This issue seems to be salient in
      infertile women who suffer from psychological consequences of infertility. This
      study was conducted to investigate the relationship of body image with sexual
      function and marital adjustment in infertile women in 2011 in Mashhad, Iran.
      MATERIALS AND METHODS: This correlational study was performed on 130 infertile
      women who referred to Montaserieh Infertility Research Centre in Mashhad, Iran.
      Subjects were selected using convenient sampling method. To collect data, valid
      and reliable questionnaires including demographic and infertility-related data
      tool, modified Younesi Body Image Questionnaire, Rosen Female Sexual Function
      Index (FSFI), and Spanier Dyadic Adjustment Scale (DAS) were used. Data analysis
      was performed by SPSS software using Student's t-test, correlation, analysis of
      variance (ANOVA), and Tukey post-hoc test. RESULTS: The mean scores of body
      image, sexual function, and marital adjustment in women were 308.1 +/- 45.8,
      27.23 +/- 3.80, and 113.8 +/- 19.73, respectively. There was a direct correlation
      between overall body image and subscales of sexual function including sexual
      arousal (P = 0.003), sexual desire (P = 0.024), vaginal moisture (P = 0.001),
      orgasm (P < 0.001), sexual satisfaction (P < 0.001), and dyspareunia (P = 0.007).
      A direct correlation was also observed between overall body image and subscales
      of marital adjustment including agreement and consent (P < 0.001), satisfaction
      with life (P < 0.001), continuity of life (P = 0.007), and expressing emotions
      within the family environment (P < 0.001). CONCLUSIONS: Improved sexual function
      and marital adjustment in cases with higher body image provides evidence that one
      of the solutions to reduce sexual dysfunction and marital dispute in infertile
      women could be planning educational and counseling programs to improve women's
      body image.

PMID- 25949253
TI  - The effect of spouses' educational classes held for primiparous women referring
      to Hajar hospital on their quality of life and pregnancy outcomes.
AB  - BACKGROUND: With regard to the importance of quality of life in pregnant women,
      the present study aimed to determine the effect of spouses' educational classes
      held for primaparous women referring to Hajar hospital on women's quality of life
      and pregnancy outcomes. MATERIALS AND METHODS: This clinical trial was conducted
      from September 2011 to June 2012 in the clinic of the Hajar university center in
      Shahrekord. Eligible primiparous women who registered for physiologic delivery
      educational classes were randomly assigned to study (n = 31) and control (n = 27)
      groups. In the control group, eight physiologic delivery educational sessions
      were held. In the study group, in addition to attendance of pregnant women, their
      husbands also attended the third and the eighth sessions of these classes.
      Women's quality of life was investigated with SF36 questionnaire and pregnancy
      outcomes after delivery were investigated. Data were analyzed by t-test and Chi
      square test. RESULTS: Before intervention, there was no significant difference
      between scores of quality of life and demographic characteristics (P > 0.05).
      After intervention, there was a significant difference only in the dimensions of
      mental health, hugging time, kissing, and breast feeding between the study and
      control groups (P < 0.05). There was no significant difference in gestational
      age, gravida, number of miscarriages, pregnancy outcomes, and spouses' age (P >
      0.05). CONCLUSIONS: Educational classes held for the pregnant women's husbands
      during pregnancy can be efficient in promotion of pregnant women's quality of
      life, especially in improving their mental health.

PMID- 25949254
TI  - Incentives for self-management after coronary artery bypass graft surgery.
AB  - BACKGROUND: Chronic illnesses such as coronary heart disease are among the most
      prevalent and costly of all global health problems. Coronary heart disease is a
      leading cause of death worldwide, including Iran. One aspect of living with
      chronic illness is self-management which can reduce the impact of illness on
      daily life and maintain the quality of life. A qualitative understanding of how
      patients perceive the necessity of self-management is important for self
      management support. The current study aims to determine patients' perception of
      the need for self-management following coronary artery bypass graft (CABG)
      surgery. MATERIALS AND METHODS: We used a content analysis approach to conduct
      this qualitative study. Data were collected by interviews with 25 patients who
      underwent CABG surgery at least 1 year prior to the study. Purposeful, followed
      by theoretical sampling was used until data saturation. Data were analyzed by
      descriptive qualitative content analysis according to the Graneheim and Lundman
      approach. RESULTS: Participants had different perceptions regarding the need for
      self-management. Three themes, "reflective thinking," "information revision," and
      "beliefs influences," comprised the basis of forming patients' perceptions to the
      need for self-management. CONCLUSIONS: Patients' perceptions vary regarding the
      need for self-management. The difference in perception should be the basis for
      training programs to guide CABG patients for successful self-management.

PMID- 25949255
TI  - Experiences of pregnancy among Iranian adolescents: A qualitative study.
AB  - BACKGROUND: Pregnancy rate among Iranian adolescents below 20 years of age is
      increasing. Pregnancy during adolescence is considered a social issue associated
      with medical, emotional, and social outcomes for the mother, child, and family.
      The current research examines the experience of pregnancy among Iranian
      adolescents. MATERIALS AND METHODS: The qualitative content analysis method was
      used. A purposive sample of 14 pregnant adolescents was enrolled in the study.
      Deep interviews were carried out with them. RESULTS: Three themes were came up
      after analyzing the interviews: 1. Psychological reactions including three
      subthemes of feelings, concerns, and fears; 2. physical reactions including the
      subthemes of symptoms and feelings; and 3. spiritual reactions including
      religious beliefs and faith. CONCLUSIONS: The present study showed that for the
      purpose of assessing pregnancy in adolescents, one should consider the context
      and culture in which the adolescent lives. This is because factors such as
      preplanned or unwanted pregnancy and imposed or consensual marriage within or
      outside the family may draw different reactions from adolescents. Hence, all
      those factors need to be considered in order to plan health education during
      pregnancy for this age group.

PMID- 25949256
TI  - Correlate of self-care and self-neglect among community-dwelling older adults.
AB  - BACKGROUND: The prevalence of self-neglect among the elderly is expected to rise
      with a rapid increase in the growth of the older population. However, self
      neglect in the elderly and the factors related to it are not fully understood due
      to the limited research in the area, lack of consensus in the definition of the
      concept, and limited instrumentation. The purpose of this study was to
      investigate the relationship between selected socio-demographic factors on self
      care and self-neglect among older persons living in the community. MATERIALS AND
      METHODS: A cross-sectional survey design with cluster sampling was adopted for
      the study. Data were gathered from 201 older persons aged 60 years and over in
      the state of Selangor, Malaysia, through face-to-face interviews in their homes
      with a team of trained enumerators. A new instrument was developed to measure
      self-neglect. RESULTS: The internal consistency of the new instrument showed a
      reliability of 0.90. A significant bivariate relationship was noted between self
      care and self-neglect. The socio-demographic factors were also reported between
      self-care and self-neglect. CONCLUSIONS: The new instrument of elder self-neglect
      (ESN) could be used to measure self-neglect in a community dwelling. The need to
      increase the self-care skills and the capacity of self-care among older adults is
      crucial in order to reduce self-neglect and enhance their well-being.

PMID- 25949257
TI  - Living in a misty marsh: A qualitative study on the experiences of self-care
      suffering of patients with thalassemia.
AB  - BACKGROUND: Thalassemia major is the most common hereditary anemia in Iran.
      Thalassemia major patients require lifelong care and suffer much pain during self
      care. Knowledge of the nature, meaning, and impact of suffering from the
      perspective of patients is needed to determine which interventions are helpful.
      This study was designed to understand the experience of suffering in patients
      with thalassemia. MATERIALS AND METHODS: This was a qualitative study conducted
      with content analysis method. In the present study, 21 patients with thalassemia
      were selected by purposive sampling. The research was performed at Kerman Samen
      Alhojaj Medical Center, Iran, in 2013. Data collection method was conducting
      unstructured interviews using open-ended questions and field notes. In addition,
      data were analyzed using qualitative content analysis and conventional approach.
      RESULTS: Data analysis resulted in the emergence of the four central categories
      of physical exhaustion, mental and spiritual restlessness, society's behaviors
      and beliefs, and surviving a hard life, which were the suffering themes of the
      patients. CONCLUSIONS: Results showed that thalassemia in the physical,
      psychological, social, and spiritual aspects is very stressful for patients.
      Moreover, culture plays an important role in the patients' experience of
      suffering. Results of this study can help nurses improve nursing care to
      alleviate suffering based on these experiences.

PMID- 25949258
TI  - Iranian caregivers, silent mediums in caring for relatives suffering from cancer.
AB  - BACKGROUND: Poor interaction of treatment personnel with patients' families leads
      to informational contrast in families, which may ultimately increase the tension
      and pressure in these conditions. Considering the necessity of caregivers'
      contribution for an optimized treatment, continuation of care, and supporting
      patients, and with regard to caregivers' important role, and also considering the
      emphasis placed by previous studies on the significance of the caregivers'
      experiences and as there are a limited number of studies on eastern countries,
      the present study attempts to justify caregivers' understanding of their own
      needs for interaction with the treatment team. MATERIALS AND METHODS: This study
      is a qualitative research conducted through a content analysis method with an
      inductive approach. 23 familial caregivers of breast cancer patients from Seyed
      Al-Shohada and ayat- ollah khan sari Hospital of Isfahan and Arak were selected
      through purposive sampling. Data were gathered through in-depth interviews and
      field notes. The content was read for several iterations and units of meaning and
      primary codes were extracted, and then categories were extracted based on the
      centrality and similarity of meanings. RESULTS: Four categories were extracted:
      a) caregivers' contribution and acknowledging them in the treatment system, b)
      training in efficient caregiving, c) efficient interaction of the medical team
      with caregivers, and d) easy and dynamic access to the medical services.
      CONCLUSIONS: The results of the study showed that family caregivers should
      cooperate and interact with the medical team. They also need training from the
      medical team on caregiving to cancer patients. An understanding of caregivers'
      experiences and needs in their interaction with the medical team and identifying
      their needs as an important aspect in cancer care system assists in designing
      evidence-based healthcare interventions and a comprehensive family-cantered care
      program.

PMID- 25949259
TI  - Impact of interferential current on recovery of pressure ulcers grade 1 and 2.
AB  - BACKGROUND: Pressure ulcers' treatment imposes a considerable cost on health
      system and patients. Electrical stimulation has already been introduced as an
      effective method for promoting wound healing. This study was conducted to
      determine the impact of interferential current (IF) on healing of pressure ulcers
      (grade1 and 2). MATERIALS AND METHODS: In this clinical trial, 23 patients (12 as
      cases and 11 as controls) were recruited. The study group was treated with IF
      daily for 10 days. IF current was applied via isoplanar current with a sweep
      frequency of 30-99 Hz and with tolerable intensity for 15-20 min. Before
      intervention, condition of the wounds was assessed and recorded. Routine
      characteristics of the ulcers in both groups were recorded before intervention
      (first day) and on the fifth and tenth days after intervention. SPSS (ver. 13)
      with paired t-test and Fisher's exact test was also used to analyze the data. A P
      value of 0.05 was considered significant. RESULTS: According to one-sample
      Kolmogorov-Smirnov test, demographic characteristics, features of ulcer, as well
      as the intensity of pain were not significantly different between the study and
      control groups. All patients in the control and study groups were complaining of
      pain (7.25 +/- 1.21 in the intervention group vs. 6.35 +/- 1.28 in the control
      group). Ulcer size decreased significantly in the study group (P = 0.012) with a
      significant reduction in pain intensity (P = 0.000), amount of discharge (P =
      0.008), and level of edema (P = 0.000), compared to controls. CONCLUSION: As a
      first study in this field, the results showed that the use of IF current can
      accelerate pressure ulcer healing and reduce its size. As IF current can be
      considered as a deeper form of Transcutaneous Electrical Nerve Stimulation
      (TENS), it seems to be a safe method with no side effects.

PMID- 25949260
TI  - The study of predicting role of personality traits in the perception of labor
      pain.
AB  - BACKGROUND: Labor pain is one of the most intense pains experienced by women.
      Different factors including physiological, psychological, socio-cultural,
      environmental, and personality-related factors are relevant to perception of
      childbirth pain. The negative experience of pain causes mental, psychological
      problems and influences the relationship between the mother and infant.
      Therefore, considering the importance of women's health, this study was conducted
      to examine the predicting role of personality traits on perception of labor pain
      among pregnant women in Kazeroun, Fars Province, Iran. MATERIALS AND METHODS:
      This study is a correlational descriptive-analytical study. The data were
      collected using big five factors questionnaire about personality traits
      (neuroticism, openness experience, agreeableness, conscientiousness, and
      extraversion) and a researcher-made questionnaire on the perception of labor pain
      (containing items such as reaction to pain, pain intolerance, pain depth, and
      pain acceptance) from 220 parturient women who referred to Valiasr Hospital in
      Kazeroun. The data were analyzed using statistical methods including Pearson
      correlation coefficient, factor analysis, and multiple regression analysis. All
      analyses were carried out with SPSS. RESULTS: The results of the study indicated
      that among the factors influencing the perception of labor pain, the reaction to
      pain was meaningfully predicted by the personality dimensions of neuroticism
      (beta =0.26, P < 0.01) and openness experience (beta =0.20, P < 0.05).
      Neuroticism (beta =0.20, P < 0.05) and openness experience (beta =0.20, P < 0.05)
      were the positive predicting factors and conscientiousness (beta = -0.20, P <
      0.05) was a negative predicting factor for labor pain intolerance. Agreeableness
      (beta =0.31, P < 0.01), neuroticism (beta =0.20, P < 0.01), and openness
      experience (beta =0.18, P < 0.01) were the predictive factors for pain depth.
      Among all personality traits, neuroticism (beta =0.19, P < 0.05) and openness
      experience (beta =0.20, P < 0.05) were the positive predictive factors and
      conscientiousness (beta = -0.24, P < 0.05) was the negative predictive factor for
      the total score of the perception of labor pain. CONCLUSIONS: It is recognized
      that personality traits can have predictive roles in the perception of labor
      pain. As a result, using different methods in managing and reducing childbirth
      pain, along with good advice and suitable education in pregnancy based on
      personality traits of women can be helpful for mothers to have more pleasurable
      experience from childbirth.

PMID- 25949261
TI  - Developing traditional chinese medicine in the era of evidence-based medicine:
      current evidences and challenges.
AB  - Evidence-based medicine (EBM), by integrating individual clinical expertise with
      the best available clinical evidence from systematic research, has in recent
      years been established as the standard of modern medical practice for greater
      treatment efficacy and safety. Traditional Chinese Medicine (TCM), on the other
      hand, evolved as a system of medical practice from ancient China more than 2000
      years ago based on empirical knowledge as well as theories and concepts which are
      yet to be mapped by scientific equivalents. Despite the expanding TCM usage and
      the recognition of its therapeutic benefits worldwide, the lack of robust
      evidence from the EBM perspective is hindering acceptance of TCM by the Western
      medicine community and its integration into mainstream healthcare. For TCM to
      become an integral component of the healthcare system so that its benefits can be
      rationally harnessed in the best interests of patients, it is essential for TCM
      to demonstrate its efficacy and safety by high-level evidence in accordance with
      EBM, though much debate remains on the validity and feasibility of applying the
      EBM model on this traditional practice. This review aims to discuss the current
      status of research in TCM, explore the evidences available on its efficacy and
      safety, and highlight the issues and challenges faced in applying EBM to TCM. 

PMID- 25949262
TI  - Medication and Dietary Supplement Interactions among a Low-Income, Hospitalized
      Patient Population Who Take Cardiac Medications.
AB  - Purpose. To identify characteristics associated with the use of potentially
      harmful combinations of dietary supplements (DS) and cardiac prescription
      medications in an urban, underserved, inpatient population. Methods. Cardiac
      prescription medication users were identified to assess the prevalence and risk
      factors of potentially harmful dietary supplement-prescription medication
      interactions (PHDS-PMI). We examined sociodemographic and clinical
      characteristics for crude (chi (2) or t-tests) and adjusted multivariable
      logistic regression associations with the outcome. Results. Among 558 patients,
      there were 121 who also used a DS. Of the 110 participants having a PHDS-PMI, 25%
      were asked about their DS use at admission, 75% had documentation of DS in their
      chart, and 21% reported the intention to continue DS use after discharge. A
      multivariable logistic regression model noted that for every additional
      medication or DS taken the odds of having a PHDS-PMI increase and that those with
      a high school education are significantly less likely to have a PHDS-PMI than
      those with a college education. Conclusion. Inpatients at an urban safety net
      hospital taking a combination of cardiac prescription medications and DS are at a
      high risk of harmful supplement-drug interactions. Providers must ask about DS
      use and should consider the potential for interactions when having patient
      discussions about cardiac medications and DS. 

PMID- 25949263
TI  - Gastroprotective Effect of Geopropolis from Melipona scutellaris Is Dependent on
      Production of Nitric Oxide and Prostaglandin.
AB  - The aim of this study was to evaluate the gastroprotective activity of ethanolic
      extract of geopropolis (EEGP) from Melipona scutellaris and to investigate the
      possible mechanisms of action. The gastroprotective activity of the EEGP was
      evaluated using model ulcer induced by ethanol. To elucidate the possible
      mechanisms of action, we investigated the involvement of the nonprotein
      sulfhydryl (NP-SH) groups, nitric oxide and prostaglandins. In addition, the
      antisecretory activity of EEGP was also evaluated by pylorus ligated model. The
      EEGP orally administrated (300 mg/kg) reduced the ulcerative lesions induced by
      the ethanol (P < 0.05). Regarding the mechanism of action, the prior
      administration of nitric oxide and prostaglandins antagonists suppressed the
      activity of gastroprotective EEGP (P < 0.05). On the other hand the
      gastroprotective activity of EEGP was kept in the group pretreated with the
      antagonist of the NP-SH groups; furthermore the antisecretory activity was not
      significant (P > 0.05). These results support the alternative medicine use of
      geopropolis as gastroprotective and the activities observed show to be related to
      nitric oxide and prostaglandins production. 

PMID- 25949264
TI  - Chemical Composition and Larvicidal Activity of Essential Oils Extracted from
      Brazilian Legal Amazon Plants against Aedes aegypti L. (Diptera: Culicidae).
AB  - The mosquito Aedes aegypti L. (Diptera: Culicidae) is the major vector of dengue
      and chikungunya fever. The lack of effective therapies and vaccines for these
      diseases highlights the need for alternative strategies to control the spread of
      virus. Therefore, this study investigated the larvicidal potential of essential
      oils from common plant species obtained from the Chapada das Mesas National Park,
      Brazil, against third instar A. aegypti larvae. The chemical composition of these
      oils was determined by gas chromatography coupled to mass spectrometry. The
      essential oils of Eugenia piauhiensis Vellaff., Myrcia erythroxylon O. Berg,
      Psidium myrsinites DC., and Siparuna camporum (Tul.) A. DC. were observed to be
      mainly composed of sesquiterpene hydrocarbons. The essential oil of Lippia
      gracilis Schauer was composed of oxygenated monoterpenes. Four of the five tested
      oils were effective against the A. aegypti larvae, with the lethal concentration
      (LC50) ranging from 230 to 292 mg/L after 24 h of exposure. Overall, this work
      demonstrated the possibility of developing larvicidal products against A. aegypti
      by using essential oils from the flora of the Brazilian Legal Amazon. This in
      turn demonstrates the potential of using natural resources for the control of
      disease vectors. 

PMID- 25949265
TI  - Ferulic Acid Attenuates TGF-beta1-Induced Renal Cellular Fibrosis in NRK-52E
      Cells by Inhibiting Smad/ILK/Snail Pathway.
AB  - Renal fibrosis is a common cause of renal dysfunction with chronic kidney
      disease. Central to this process is epithelial-mesenchymal transformation (EMT)
      of proximal tubular epithelial cells driven by transforming growth factor-beta1
      (TGF-beta1) signaling. The present study aimed to investigate the effect of
      Ferulic acid (FA) on EMT of renal proximal tubular epithelial cell line (NRK-52E)
      induced by TGF-beta1 and to elucidate its underlying mechanism against EMT
      related to TGF-beta1/Smads pathway. The NRK-52E cells were treated for 48 h with
      TGF-beta1 (5 ng/mL) in different concentrations of FA (0 to 200 uM). Fibronectin,
      a mesenchymal marker, was assessed by western blotting. Western blotting was also
      used to examine the EMT markers (E-cadherin, and alpha-smooth muscle actin (alpha
      SMA)), signal transducer (p-Smad2/3), and EMT initiator (Snail). ILK was also
      assayed by western blotting. The results showed that TGF-beta1 induced spindle
      like morphological transition in NRK-52E cells. Smad2/3 signaling pathway
      activation, increased fibronectin, alpha-SMA, ILK, and Snail expression, and
      decreased E-cadherin expression in TGF-beta1-treated NRK-52E cells. FA
      efficiently blocked P-Smad2/3 activation and attenuated all these EMT changes
      induced by TGF-beta1. These findings suggest that FA may serve as a potential
      fibrosis antagonist for renal proximal tubule cells by inhibiting EMT process. 

PMID- 25949266
TI  - The effectiveness of the feldenkrais method: a systematic review of the evidence.
AB  - The Feldenkrais Method (FM) has broad application in populations interested in
      improving awareness, health, and ease of function. This review aimed to update
      the evidence for the benefits of FM, and for which populations. A best practice
      systematic review protocol was devised. Included studies were appraised using the
      Cochrane risk of bias approach and trial findings analysed individually and
      collectively where possible. Twenty RCTs were included (an additional 14 to an
      earlier systematic review). The population, outcome, and findings were highly
      heterogeneous. However, meta-analyses were able to be performed with 7 studies,
      finding in favour of the FM for improving balance in ageing populations (e.g.,
      timed up and go test MD -1.14 sec, 95% CI -1.78, -0.49; and functional reach test
      MD 6.08 cm, 95% CI 3.41, 8.74). Single studies reported significant positive
      effects for reduced perceived effort and increased comfort, body image
      perception, and dexterity. Risk of bias was high, thus tempering some results.
      Considered as a body of evidence, effects seem to be generic, supporting the
      proposal that FM works on a learning paradigm rather than disease-based
      mechanisms. Further research is required; however, in the meantime, clinicians
      and professionals may promote the use of FM in populations interested in
      efficient physical performance and self-efficacy. 

PMID- 25949267
TI  - Xanthohumol induces growth inhibition and apoptosis in ca ski human cervical
      cancer cells.
AB  - We investigate induction of apoptosis by xanthohumol on Ca Ski cervical cancer
      cell line. Xanthohumol is a prenylated chalcone naturally found in hop plants,
      previously reported to be an effective anticancer agent in various cancer cell
      lines. The present study showed that xanthohumol was effective to inhibit
      proliferation of Ca Ski cells based on IC50 values using sulforhodamine B (SRB)
      assay. Furthermore, cellular and nuclear morphological changes were observed in
      the cells using phase contrast microscopy and Hoechst/PI fluorescent staining. In
      addition, 48-hour long treatment with xanthohumol triggered externalization of
      phosphatidylserine, changes in mitochondrial membrane potential, and DNA
      fragmentation in the cells. Additionally, xanthohumol mediated S phase arrest in
      cell cycle analysis and increased activities of caspase-3, caspase-8, and caspase
      9. On the other hand, Western blot analysis showed that the expression levels of
      cleaved PARP, p53, and AIF increased, while Bcl-2 and XIAP decreased in a dose
      dependent manner. Taken together, these findings indicate that xanthohumol
      induced cell death might involve intrinsic and extrinsic apoptotic pathways, as
      well as downregulation of XIAP, upregulation of p53 proteins, and S phase cell
      cycle arrest in Ca Ski cervical cancer cells. This work suggests that xanthohumol
      is a potent chemotherapeutic candidate for cervical cancer. 

PMID- 25949268
TI  - What proportions of focal liver lesions detected by unenhanced ultrasound are
      inconclusive?
AB  - In August 2012, the National Institute for Health and Care Excellence produced
      positive diagnostics guidance on the ultrasound contrast agent SonoVue(r), but
      recommended further research involving an estimation of the proportion of
      unenhanced ultrasound scans reporting, but not characterising, focal liver
      lesions, particularly in cirrhotic livers. Patient records from the Radiology
      Information System of an acute hospital trust were progressively filtered based
      on categorical fields and keywords in the free text reports, to obtain ultrasound
      records including the liver that were appropriate for manual analysis. In total,
      21,731 records referred from general practice or out-patient clinics were
      analysed. Patients described as having cirrhosis were analysed as a subgroup.
      After automatic exclusion of records considered likely to be negative, 5812
      records were manually read and categorised as focal liver lesion inconclusive,
      benign or malignant. In the general practice cohort of 9175 records, 746 reported
      the presence of one or more focal liver lesions, with 18.4% (95% CI 15.7% to
      21.3%) of these records mentioning an inconclusive focal liver lesion. In the out
      patient cohort of 12,556 records, 1437 reported one or more focal liver lesions,
      and 29.4% (95% CI 26.9% to 32.0%) of these were inconclusive. Cirrhosis was
      reported in 10.8% of the out-patient scans that also reported a focal liver
      lesion, and 47.4% (95% CI 39.3% to 55.6%) of these scans had an inconclusive
      focal liver lesion, compared with 27.3% (95% CI 24.9% to 29.8%) that were
      inconclusive in non-cirrhotic livers (odds ratio 2.4; 95% CI 1.7 to 3.4). This
      retrospective study indicates that unenhanced ultrasound scans, in which a focal
      liver lesion is detected, are frequently inconclusive, with the probability of an
      inconclusive scan being greater in out-patient than general practice referrals.
      Inconclusive focal liver lesions were also reported in greater proportions of
      cirrhotic than non-cirrhotic livers. The results of this research will inform
      future updates of National Institute for Health and Care Excellence diagnostics
      guidance.

PMID- 25949269
TI  - The difficult management of disseminated Sporothrix brasiliensis in a patient
      with advanced AIDS.
AB  - Sporotrichosis is an infection caused by a dimorphic fungus of the Sporothrix
      schenckii complex. Host immunity is an important factor in the clinical
      manifestations of the disease. Deeply immunocompromised individuals, especially
      those infected with the Human Immunodeficiency Virus (HIV) and T CD4 counts < 350
      cells/ul lymphocytes, may present with the systemic form of sporotrichosis. This
      report describes a case of disseminated sporotrichosis caused by S. brasiliensis
      in a patient with advanced AIDS. The skin, lungs, bones and central nervous
      system were affected. Medical treatment involved the administration of
      amphotericin B, terbinafine, itraconazole and posaconazole. Posaconazole was
      associated with the best clinical response and clearing of the fungus from the
      central nervous system. 

PMID- 25949270
TI  - Bibliometric profile of the global scientific research on methanol poisoning
      (1902-2012).
AB  - BACKGROUND: Methanol poisoning is on the rise and has been associated with high
      morbidity and mortality; it has resulted in growing research in the field of
      toxicology. The aim of this study was to reveal underlying patterns in scientific
      outputs related to methanol poisoning at the global level by evaluating different
      bibliometric indices. METHODS: We searched for publications that contained
      specific words regarding methanol poisoning in Scopus database. RESULTS: A total
      of 912 articles, with 8,317 citations and with an average of 9.1 citations per
      document, were retrieved on methanol poisoning, and the bulk of the articles were
      published from the USA (20.9%), followed by Spain (4.4%), Canada (4.3%), India
      (3.1%), and France (3.0%). The articles were published belonging to 57 countries.
      No data related to methanol poisoning were published from 155 (73.1%) out of 212
      countries. Twenty-one documents (2.3%) were published in Clinical Toxicology,
      whereas 18 (2.0%) were published in The Lancet. CONCLUSIONS: Scientific
      production related to methanol poisoning is increasing. articles have been
      published in a wide range of journals with a variety of subject areas, most
      notably clinical toxicology; and the country with the greatest production was the
      USA.

PMID- 25949271
TI  - Optimal control strategy for abnormal innate immune response.
AB  - Innate immune response plays an important role in control and clearance of
      pathogens following viral infection. However, in the majority of virus-infected
      individuals, the response is insufficient because viruses are known to use
      different evasion strategies to escape immune response. In this study, we use
      optimal control theory to investigate how to control the innate immune response.
      We present an optimal control model based on an ordinary-differential-equation
      system from a previous study, which investigated the dynamics and regulation of
      virus-triggered innate immune signaling pathways, and we prove the existence of a
      solution to the optimal control problem involving antiviral treatment or/and
      interferon therapy. We conduct numerical experiments to investigate the treatment
      effects of different control strategies through varying the cost function and
      control efficiency. The results show that a separate treatment, that is, only
      inhibiting viral replication (u1(t)) or enhancing interferon activity (u2(t)),
      has more advantages for controlling viral infection than a mixed treatment, that
      is, controlling both (u1(t)) and (u2(t)) simultaneously, including the smallest
      cost and operability. These findings would provide new insight for developing
      effective strategies for treatment of viral infectious diseases.

PMID- 25949272
TI  - Relationship between bone density and bone metabolism in adolescent idiopathic
      scoliosis.
AB  - Several authors have confirmed that 27 to 38% of AIS patients had osteopenia. But
      few studies have assessed bone metabolism in AIS. This study assessed bone
      mineral density and bone metabolism in AIS patients using the bone metabolism
      markers, BAP and TRAP5b. The subjects were 49 consecutive adolescent AIS patients
      seen at our institutes between March 2012 and September 2013. Sixty-five percent
      of AIS patients had osteopenia or osteoporosis and 59% of AIS patients had high
      values for TRAP5b. The AIS patients with high values of TRAP5b had lower Z scores
      than those with normal values of TRAP5b. Higher rates of bone resorption are
      associated with low bone density in AIS patients. 

PMID- 25949273
TI  - Complications associated with surgical repair of syndromic scoliosis.
AB  - BACKGROUND: There are a number of syndromes that have historically been
      associated with scoliosis e.g.: Marfan, Down, and Neurofibromatosis. These
      syndromes have been grouped together as one etiology of scoliosis, known as
      syndromic scoliosis. While multiple studies indicate that these patients are at
      high risk for perioperative complications, there is a paucity of literature
      regarding the collective complication rates and surgical needs of this
      population. METHODS: PubMed and Embase databases were searched for literature
      encompassing the surgical complications associated with the surgical management
      of patients undergoing correction of scoliosis in the syndromic scoliosis
      population. Following exclusion criteria, 24 articles were analyzed for data
      regarding these complications. RESULTS: The collective complication rates and
      findings of these articles were categorized based on specific syndrome. The rates
      and types of complications for each syndrome and the special needs of patients
      with each syndrome are discussed. Several complication trends of note were
      observed, including but not limited to the universally nearly high rate of wound
      infections (>5% in each group), high rate of pulmonary complications in patients
      with Rett syndrome (29.2%), high rate (>10%) of dural tears in Marfan and Ehlers
      Danlos syndrome patients, high rate (>20%) of implant failure in Down and Prader
      Willi syndrome patients, and high rate (>25%) of pseudarthrosis in Down and
      Ehlers-Danlos patients. CONCLUSIONS: Though these syndromes have been classically
      grouped together under the umbrella term "syndromic," there may be specific needs
      for patients with each of these ailments. Given the high rate of complications,
      further research is necessary to understand the unique needs for each of these
      patient groups in the preoperative, intraoperative, and postoperative settings.

PMID- 25949274
TI  - Axial pullout strength comparison of different screw designs: fenestrated screw,
      dual outer diameter screw and standard pedicle screw.
AB  - BACKGROUND: The pullout strength of pedicle screws is influenced by many factors,
      including diameter of the screws, implant design, and augmentation with bone
      cement such as PMMA. In the present study, the pullout strength of an innovative
      fenestrated screw augmented with PMMA was investigated and was compared to
      unaugmented fenestrated, standard and dual outer diameter screw. METHODS: Twenty
      four thoracolumbar vertebrae (T10-L5, age 60 to 70 years) from three cadavers
      were implanted with the four different pedicle screws. Twelve screws of each type
      were instrumented into either left or right pedicle with standard screw paired
      with unaugmented and dual outer diameter screw paired with augmented fenestrated
      screw in any given vertebra. Axial pullout testing was conducted at a rate of 5
      mm/min. Force to failure (Newtons) for each pedicle screw was recorded. RESULTS:
      The augmented fenestrated screws had the highest pullout strength, which
      represented an average increase of 149%, 141%, and 78% in comparison to
      unaugmented, standard, and dual outer diameter screws, respectively. Pullout
      strength of unaugmented screws was comparable to that of standard screws, however
      it was significantly lower than dual outer diameter screws. CONCLUSIONS:
      Fenestrated screws augmented with PMMA improve the fixation strength and result
      in significantly higher pullout strength compared to dual outer diameter,
      standard and unaugmented fenestrated screws. Screws with dual outer diameter
      provided enhanced bone-screw purchase and may be considered as an alternative
      technique to increase the bone-screw interface in cases where augmentation using
      bone cement is not feasible. Unaugmented screws can be left in the pedicle even
      without cement and provide similar pullout strength to standard screws.

PMID- 25949277
TI  - A novel disease-causing mutation in AVPR2: Q96H.
AB  - A 4-month-old male infant was diagnosed with nephrogenic diabetes insipidus
      (NDI). Genetic testing of the arginine vasopressin receptor-2 (AVPR2) yielded a
      novel X-linked mutation, termed Q96H, in both the propositus and his mother;
      there was no family history. Protein sequence comparison between AVPR subtypes
      shows that Q96 is part of a highly conserved motif. Many other disease-causing
      mutations, confirmed with in vitro expression studies, map to surrounding
      residues. Molecular modelling studies showed that the equivalent residue in AVPR1
      is likely critical for vasopressin binding. We posit that Q96 must be important
      for the integrity of AVPR2 function. 

PMID- 25949275
TI  - The prevention of acute kidney injury an in-depth narrative review: Part 2: Drugs
      in the prevention of acute kidney injury.
AB  - The second part of this in-depth clinical review focuses on drugs used in the
      prevention of AKI in the patient at risk and/or in the management of the patient
      with incipient AKI. Among the drugs used to maintain a normal renal perfusion
      pressure, norepinephrine and vasopressin are most commonly used in hypotensive
      critically ill patients. The most recent RCT did not find a difference between
      low-dose vasopressin plus norepinephrine and norepinephrine alone in patients
      with septic shock, suggesting that either approach is reasonable. However,
      vasopressin may be beneficial in the less severe septic shock subgroup. Loop
      diuretics may convert an oliguric into a non-oliguric form of AKI that may allow
      easier fluid and/or nutritional support of the patient. Volume overload in AKI
      patients is common and diuretics may provide symptomatic benefit in that
      situation. However, loop diuretics are neither associated with improved survival,
      nor with better recovery of renal function in AKI. Among the renal vasodilating
      drugs, the routine administration of dopamine to patients for the prevention of
      AKI or incipient AKI is no longer justified. On the other hand, although
      additional studies may be warranted, fenoldopam may appear to be a likely
      candidate for the prevention of AKI, particularly in critically ill patients, if
      the positive results obtained in some recent studies are confirmed. Trials with
      natriuretic peptides were in general inconclusive but despite the fact that
      nesiritide is currently approved by the FDA only for the treatment of heart
      failure, this vasodilator may in the future play a role in the prevention of AKI,
      particularly in association with heart failure and cardiac surgery. The most
      recent trials seem to confirm a potential positive preventive effect of N
      acetylcysteine (NAC), particularly in contrast-induced nephropathy (CIN), NAC
      alone should never take the place of IV hydration in patients at risk for CIN;
      fluids likely have a more substantiated benefit. At present, initiation of statin
      therapy for the prevention of CIN cannot be recommended, but these drugs should
      not be stopped before a radiological intervention in patients on chronic statin
      therapy. Rasburicase is very effective in the prevention of acute tumour lysis
      syndrome. Erythropoietin (EPO) has tissue-protective effects and prevents tissue
      damage during ischaemia and inflammation, and currently trials are performed with
      EPO in the prevention of AKI post-cardiac surgery, CIN and post-kidney
      transplantation. From this review it becomes clear that single-drug therapy will
      probably never be effective in the prevention of AKI and that multiple agents may
      be needed to improve outcomes. In addition, drugs should be administered early
      during the course of the disease. 

PMID- 25949276
TI  - Role of citrate and other methods of anticoagulation in patients with severe
      liver failure requiring continuous renal replacement therapy.
AB  - Anticoagulation is required during continuous renal replacement therapy to
      prevent filter clotting and optimize filter performance. However, anticoagulation
      may also be associated with serious bleeding complications. Patients with liver
      failure often suffer from underlying coagulopathy and are especially prone to
      anticoagulation complications. The aim of this review is to present the unique
      features of patients with hepatic injury in terms of anticoagulation disorders
      and to analyze data on safety and efficacy of the different anticoagulation
      methods for liver failure patients undergoing continuous renal replacement
      therapy. 

PMID- 25949278
TI  - Surreptitious hyperkalaemia and its complications.
AB  - Surreptitious hyperkalaemia is not a common problem, particularly in patients not
      yet dialysis dependent. We encountered a patient who baffled her physicians and
      their consultants, who nonetheless proposed life-saving treatments and novel
      explanations. However, according to the maxim that common things are common and
      rare things are rare, we solved the problem by focusing on the accompanying
      anion. 

PMID- 25949279
TI  - Electrolyte disturbances and acute kidney injury induced by imatinib therapy.
AB  - Imatinib mesylate is an anticancer agent that selectively inhibits protein
      kinases involved in the pathophysiology of cancer. It is now the first-line
      therapy for patients with chronic myeloid leukaemia (CML) and is generally well
      tolerated. Here, we describe a case of a patient receiving imatinib for CML. The
      patient developed renal failure accompanied by severe hypophosphataemia,
      hypokalaemia and hypomagnesaemia. We discuss the pathophysiological
      characteristics of imatinib-induced renal injury, and we demonstrate that these
      electrolyte disturbances were caused by increased urinary excretion of phosphate
      and potassium. Early diagnosis and correction of imatinib-induced renal injury
      and electrolyte disorders can improve clinical outcomes. 

PMID- 25949280
TI  - Cystinuria in a patient with polycystic kidney disease.
AB  - Cystinuria is a rare autosomal recessive metabolic disorder of renal and
      intestinal cystine transport. Cystine stones are found in only 1-2% of all stone
      formers. Patients with cystinuria are at high risk for nephrolithiasis and
      subsequent morbidity. Our patient is a 37-year-old male who presented for routine
      follow-up for polycystic kidney disease (PKD). He denied any history of passing
      nephroliths. He had no family history of PKD or personal history of kidney
      stones. Serum creatinine was 1.2 mg%. On routine urine microscopy, he was found
      to have multiple hexagonal cystine crystals. Urine pH was 7.5. Renal CT scan
      revealed enlarged polycystic kidneys and scattered bilateral intra-renal calculi.
      Urinary quantification of cystine was 1645 mg/day (normal excretion rate 30
      mg/day). Patients with PKD are at increased risk for nephrolithiasis for a number
      of reasons including urinary acidification, concentrating defects and
      hypocitraturia. The molecular, cellular and genetic basis for cystinuria is
      distinctly different and presumably unrelated to the genetic defects in PKD. We
      suspect that the occurrence of these two unrelated genetic diseases in the same
      patient is a coincidental finding. Even after a thorough review of the published
      literature, we were unable to find a genetic relationship between cystinuria and
      cystic renal diseases. To our knowledge, this is the first report of a finding of
      cystinuria in an adult with PKD. 

PMID- 25949281
TI  - Familial clusters of ANCA small-vessel vasculitis.
AB  - Small-vessel vasculitides associated with the presence of antineutrophil
      cytoplasmic antibodies in the serum are characterized by inflammation and
      necrosis of small vessels. A pauci-immune necrotizing crescentic
      glomerulonephritis typically occurs when there is renal damage. Pathogenesis of
      these diseases remains unclear although infectious, genetic and environmental
      factors have been involved. Few familial clusters of antineutrophil cytoplasmic
      antibodies' small-vessel vasculitis are described in the literature. We report
      two families with first-degree relatives affected with antineutrophil cytoplasmic
      antibodies' small-vessel vasculitis. 

PMID- 25949282
TI  - Progressive bevacizumab-associated renal thrombotic microangiopathy.
AB  - Vascular endothelial growth factor (VEGF) is integral to the integrity of the
      glomerular filtration barrier. Bevacizumab is a humanized monoclonal antibody
      directed against VEGF with expanding clinical applications for metastatic solid
      tumours. We describe a case of a 61-year-old female with ovarian cancer and
      baseline chronic kidney disease who received three doses of bevacizumab and
      subsequently developed progressive renal clearance dysfunction and nephrotic
      range proteinuria. A renal biopsy was performed 4 months after drug
      discontinuation and was consistent with TMA. At baseline, prior to bevacizumab
      exposure, her estimated glomerular filtration rate (eGFR) was 44 mL/min/1.73 m(2)
      and she had no proteinuria. At the completion of therapy, eGFR was 27 mL/min/1.73
      m(2) with 1+ proteinuria on urinalysis. Her renal failure and proteinuria
      continued to progress 5 months after discontinuation of bevacizumab therapy, at
      which time eGFR was 11 mL/min/1.73 m(2) and proteinuria was 5.5 g/24 h. Non
      remitting TMA after bevacizumab therapy in patients with pre-existing chronic
      kidney disease has not been previously reported. Further studies are needed to
      assess the safety of this drug in patients with chronic kidney disease. 

PMID- 25949284
TI  - Haemochromatosis in end-stage renal disease: when waste is a treatment option.
AB  - For patients with end-stage renal disease and hereditary haemochromatosis,
      prevention and treatment of anaemia differ from usual nephrologic guidelines.
      Monitoring of individual disease progression and ferritin levels is crucial. We
      describe a case of a young haemodialysis patient with early-stage organ
      dysfunction caused by hereditary haemochromatosis, in whom iron stores have
      successfully been depleted with phlebotomy and supplemental erythropoietin over
      22 months. Target ferritin levels could finally be reached without severe,
      persisting or symptomatic anaemia. 

PMID- 25949283
TI  - Renal cortical necrosis complicating laundry detergent ingestion.
AB  - Accidental oral detergent ingestion usually causes mild gastrointestinal
      manifestations including nausea, vomiting and diarrhea as well as upper airway
      irritation. There are a limited number of reported oral detergent ingestions
      leading to acute kidney injury, mainly due to rhabdomyolysis. We present an
      ultimately fatal case of laundry detergent ingestion leading to biopsy proven
      severe cortical necrosis and irreversible renal damage. Detergent ingestion was
      associated with widespread endothelial injury leading to a picture of thrombotic
      microangiopathy. Among the detergent ingredients ingested by the patient, sodium
      borate raised the highest concern as a potential toxin exacerbated further by
      severe hypovolaemia and consequent decrease in renal toxin excretion. As sodium
      borate is dialyzable, haemodialysis should be a consideration early after laundry
      detergent ingestion. 

PMID- 25949285
TI  - Iatrogenic arteriovenous fistula in the groin presenting as cardiac failure.
AB  - A patient presented with cardiac failure and investigations revealed a right
      femoral arteriovenous fistula (AVF) 5 weeks after the insertion of a femoral
      dialysis catheter for haemodialysis. No ultrasound had been used for catheter
      insertion. The iatrogenic AVF was repaired, and her episodes of cardiac failure
      ceased. It is recommended that femoral dialysis catheters are inserted using
      ultrasound guidance to avoid inadvertent arterial puncture. 

PMID- 25949286
TI  - Bone histomorphometry after treatment with teriparatide (PTH 1-34) in a patient
      with adynamic bone disease subsequent to parathyroidectomy.
AB  - A 33-year-old male patient suffered from adynamic bone disease because of
      parathyroidectomy due to tertiary hyperparathyroidism. Histomorphometric analysis
      of bone biopsies taken before and 8 months after treatment with teriparatide
      (human parathyroid hormone 1-34 of recombinant DNA origin) for 18 months is
      demonstrated. A considerable increase in mineralized bone volume and also
      stimulated bone remodelling were detected after treatment with teriparatide.
      Although teriparatide is currently only licenced for treatment of severe
      osteoporosis, this case shows the potential therapeutic effect of this new drug
      to improve bone structure in a patient with adynamic bone disease. 

PMID- 25949287
TI  - Post-transplant lymphoproliferative disorder: case report and review of
      susceptibility to EBV in the Scottish adult renal transplant pool.
AB  - We report a case of high-grade non-Hodgkin's lymphoma following Epstein-Barr
      virus (EBV) infection in a 38-year-old renal transplant recipient who was
      successfully treated with rituximab and remains alive 6 years later with
      reasonable graft function. We subsequently undertook a survey showing that 1.8%
      of the Scottish adult transplant pool are susceptible to EBV infection. Though a
      vaccine for EBV is currently not yet available, routine screening of potential
      renal transplant recipients for EBV should help identify those at increased risk
      of post-transplant lymhoproliferative disorder (PTLD), while tailoring of
      immunosuppression and antiviral prophylaxis with Ganciclovir may help reduce the
      emergence of this potentially life-threatening disease. 

PMID- 25949288
TI  - Whipple's disease: often a late diagnosis and a rare cause of nephropathy.

PMID- 25949289
TI  - White tide.

PMID- 25949290
TI  - When the finding of glomerular fibrils in patients with nephrotic syndrome leads
      to an erroneous diagnosis.

PMID- 25949291
TI  - Out of the blue.

PMID- 25949292
TI  - Fluindione-induced immuno-allergic interstitial nephritis.

PMID- 25949293
TI  - Pan-ureteric transitional cell carcinoma in a patient of autosomal dominant
      polycystic kidney disease with chronic renal failure.

PMID- 25949294
TI  - Acute kidney failure and an epigastric mass.

PMID- 25949296
TI  - Jaundice-associated acute kidney injury.

PMID- 25949295
TI  - Intrarenal aneurysms in the tuberous sclerosis complex.

PMID- 25949297
TI  - Interest of PET-scan in the management of severe hyperparathyroidism.

PMID- 25949298
TI  - Diagnosis of prostatitis by 18-F-fluorodeoxyglucose positron emission tomography.

PMID- 25949299
TI  - Talar callosity ('prayer foot') in a haemodialysis patient.

PMID- 25949300
TI  - Alendronate-associated focal segmental glomerulosclerosis.

PMID- 25949301
TI  - Lack of correction of secondary hyperparathyroidism long term after kidney
      transplantation despite good graft function.

PMID- 25949302
TI  - Confirming high prevalence of human herpesvirus 8 infection in chronic kidney
      disease patients in Sao Paulo, Brazil.

PMID- 25949303
TI  - Extended haemodialysis hours may improve the clinical outcome of patients on
      maintenance haemodialysis without increasing the cost.

PMID- 25949304
TI  - Identifying critically ill patients with acute kidney injury for whom renal
      replacement therapy is inappropriate: an exercise in futility?
AB  - Clinicians treating critically ill patients must consider the possibility that
      painful and expensive aggressive treatments might confer negligible benefit. Such
      treatments are often described as futile or inappropriate. We discuss the problem
      of deciding whether to initiate renal replacement therapy (RRT) for critically
      ill patients with acute kidney injury (AKI) in the context of the debate
      surrounding medical futility. The main problems in deciding when such treatment
      would be futile are that the concept itself is controversial and eludes
      quantitative definition, that available outcome data do not allow confident
      identification of patients who will not benefit from treatment and that the
      decision on RRT in a critically ill patient with AKI is qualitatively different
      from decisions on other modalities of intensive care and resuscitation, as well
      as from decisions on dialysis for chronic kidney disease. Despite these
      difficulties, nephrologists need to identify circumstances in which continued
      aggressive care would be futile before proceeding to initiate RRT. 

PMID- 25949306
TI  - What's on the web for nephrology?

PMID- 25949305
TI  - Pain management in patients with chronic kidney disease.
AB  - Pain has been reported to be a common problem in the general population and end
      stage renal disease (ESRD) patients. Although similar data for pre-ESRD patients
      are lacking, we recently reported that the prevalence of pain is also very high
      (>70%) among pre-ESRD patients at a Los Angeles County tertiary referral centre.
      The high prevalence of pain in the CKD population is particularly concerning
      because pain has been shown to be associated with poor quality of life. Of
      greater concern, poor quality of life, at least in dialysis patients, has been
      shown to be associated with poor survival. We herein discuss the pathophysiology
      of common pain conditions, review a commonly accepted approach to the management
      of pain in the general population, and discuss analgesic-induced renal
      complications and therapeutic issues specific for patients with reduced renal
      function. 

PMID- 25949307
TI  - A novel mutation in AVPR2 causing congenital nephrogenic diabetes insipidus with
      complete resistance to antidiuretic hormone.
AB  - A 6-month-old male infant presented with failure to thrive. Hypernatraemia and
      elevated serum osmolality in the presence of low urine sodium and osmolality led
      to the diagnosis of diabetes insipidus. Administration of 1-deamino-8-D-arginine
      vasopressin (dDAVP) neither decreased urine volume nor increased urine osmolality
      indicating congenital nephrogenic diabetes insipidus. Molecular analysis in the
      arginine-vasopressin receptor-2 gene (AVPR2) located on chromosome Xq28
      demonstrated a novel 5-base pair deletion (c.962-966delACCCC; g.1429
      1433delACCCC) leading to a shift of the reading frame (p.Asn321fs) and a
      premature termination codon implying an absent or non-functional protein.
      Treatment with hydrochlorothiazide, amiloride and indomethacin led to a
      favourable clinical course. 

PMID- 25949308
TI  - Multiple aetiologies of secondary hypertension in one patient.
AB  - Apart from seeking target organ damage, the investigation of hypertension is
      primarily aimed at finding a treatable cause of the hypertension. The finding of
      one such cause is usually construed as being the sole culprit responsible for the
      patient's elevated blood pressure. The existence of multiple aetiologies of
      secondary hypertension in one patient is infrequent. In this report, we describe
      such a patient in whom secondary hypertension due to Cushing's disease,
      renovascular and finally baroreflex failure was successively documented. 

PMID- 25949309
TI  - Rapamycin reduces kidney volume and delays the loss of renal function in a
      patient with autosomal-dominant polycystic kidney disease.
AB  - This is the first report of a case of a reduction in kidney volume and
      preservation of renal function in a patient with autosomal-dominant polycystic
      kidney disease (ADPKD) receiving rapamycin. A 42-year-old man with ADPKD and a
      severe persistent bleeding from his solitary left kidney was successfully treated
      with tranexamic acid (TXA). He also received low-dose rapamycin for 8 months, and
      this was associated with a 23.5% reduction in kidney volume, improvement and
      stabilization of renal function, and normalization of haemoglobin levels. When
      treatment with rapamycin was interrupted, renal function deteriorated within an 8
      month period and haemodialysis (HD) became necessary. Kidney volume increased at
      once, and life-threatening bleeding prompted a nephrectomy 4 months after the
      onset of HD. These data suggest that the reduction in kidney volume and
      preservation of renal function with rapamycin could be the result of the
      antiangiogenic, antiproliferative effects of rapamycin. 

PMID- 25949310
TI  - A rare cause of nephrotic syndrome in autosomal-dominant polycystic kidney
      disease.
AB  - We report the case of a 49-year-old lady who presented with hypertension,
      breathlessness and malaise. She was thrombocytopenic, with polycystic kidneys on
      imaging, and was found to have nephrotic syndrome. Serological results were
      consistent with systemic lupus erythematosus (SLE) and a renal biopsy confirmed
      WHO class V lupus nephritis. This is the first reported case of nephrotic
      syndrome due to lupus nephritis in a patient with autosomal dominant polycystic
      kidney disease (ADPKD) and underlines the importance of renal biopsy in patients
      with ADPKD and nephrotic range proteinuria. 

PMID- 25949311
TI  - Treatment of sarcoid granulomatous interstitial nephritis with adalimumab.
AB  - Sarcoidosis is a systemic disease with multiorgan involvement which can cause
      renal failure through several different mechanisms. Granulomatous interstitial
      nephritis is an important albeit less frequent cause of clinically significant
      renal disease. Herein, we present the case of a 46 year old woman with a history
      of sarcoidosis whom we evaluated for rapidly worsening kidney function and
      proteinuria. Renal biopsy revealed granulomatous interstitial nephritis. After
      therapy with adalimumab, her renal function improved with a significant reduction
      in proteinuria. Repeat kidney biopsy showed resolution of renal granulomata. To
      our knowledge, this is the first report of successful treatment of granulomatous
      interstitial nephritis with adalimumab. 

PMID- 25949312
TI  - Urinary tract obstruction due to extramedullary plasmacytoma: report of two
      cases.
AB  - Extramedullary plasmacytomas (EMP) rarely occur during the course of multiple
      myeloma (MM). Most frequent reported sites are superior respiratory airways,
      pleura, lung, lymph nodes, skin, subcutaneous and soft tissues, testicles and
      liver. EMP involving the urinary tract are very uncommon and have been ill
      described in the literature. We report two unusual cases of obstructive urinary
      tract EMP revealing a relapse of MM after allogeneic stem cell transplantation.
      Clinicians must be aware that EMP may be responsible for urinary tract
      obstruction even in the absence of medullary progression of MM. 

PMID- 25949313
TI  - High-output cardiac failure secondary to a large arteriovenous fistula: a
      persistent threat to the dialysis and kidney transplant patient.
AB  - High-output cardiac failure secondary to a surgically constructed arteriovenous
      fistula (AVF) is a rare entity that is usually under-diagnosed in the dialysis
      population. We herein present a case of a 35-year-old female who was diagnosed
      with high-output cardiac failure secondary to an AVF and later managed with
      surgical division of the fistula. Risk factors associated with this entity are
      discussed, and preventive screening strategies are recommended. 

PMID- 25949314
TI  - Leflunomide: a treatment option for ganciclovir-resistant cytomegalovirus
      infection after renal transplantation.
AB  - Cytomegalovirus (CMV) infection after renal transplantation is a problem of
      increasing concern resulting in significant morbidity and mortality. Widespread
      use of ganciclovir (GCV) and valganciclovir (VGCV) may cause an increase of CMV
      resistance to these first line drugs. Other treatment options are sparse and
      often complicated by adverse events, namely nephrotoxicity associated with
      foscarnet and cidofovir. Leflunomide may be another treatment option for CMV
      infections. So far it is not clear if leflunomide can also be used in the case of
      GCV-resistant CMV infections. Here we describe the use of leflunomide in two
      patients after renal transplantation with GCV-resistant CMV infections. 

PMID- 25949315
TI  - Severe adverse effects of 5-fluorouracil in S-1 were lessened by haemodialysis
      due to elimination of the drug.
AB  - S-1 and cisplatin are used as one of the first-line chemotherapies for gastric
      cancer in Japan. The plasma concentration of 5-fluorouracil (5-FU) is increased
      in patients with renal dysfunction because gimeracil in S-1 inhibits the
      degradation of 5-FU and about 50% of gimeracil is excreted in the urine. We
      describe a 35-year-old man with acute kidney injury while taking S-1 and
      cisplatin for advanced gastric cancer and who presented severe adverse effects of
      5-FU. This case report describes the evolution of the plasma concentrations of 5
      FU with haemodialysis along with a decrease in the adverse drug effects. 

PMID- 25949316
TI  - Unexpected cyanosis in a haemodialysis patient-did someone add hydrogen peroxide
      to the dialysis water?

PMID- 25949317
TI  - A case report: a patient with IgA nephropathy and coeliac disease. Complete
      clinical remission following gluten-free diet.

PMID- 25949318
TI  - An unusual cause of pleural effusion in a haemodialysis patient.

PMID- 25949319
TI  - Furosemide, orlistat and non-steroidal anti-inflammatory agents-too much for the
      kidneys to handle!

PMID- 25949320
TI  - Blunt abdominal trauma: a hidden culprit.

PMID- 25949321
TI  - No eye for ears.

PMID- 25949322
TI  - Calcineurin inhibitor toxicity in a renal transplant recipient.

PMID- 25949323
TI  - A rare cause of secondary hypertension.

PMID- 25949324
TI  - Cystic kidney disease in a patient with long-term lithium therapy.

PMID- 25949325
TI  - Acute renal allograft thrombosis in 'seronegative' antiphospholipid syndrome.

PMID- 25949326
TI  - Severe thiamine deficiency complicated by weight loss protects against renal
      ischaemia-reperfusion injury in rats.

PMID- 25949327
TI  - RET gene mutations are not a common cause of congenital solitary functioning
      kidney in adults.

PMID- 25949329
TI  - Disseminated cryptococcosis, an unusual cause of gross proteinuria in an HIV
      infected patient.

PMID- 25949328
TI  - An unconscious 76-year-old woman with renal failure and hyperechoic kidney
      lesions.

PMID- 25949330
TI  - Diabetic glomerular disease: pitfalls in diagnosis.

PMID- 25949331
TI  - How to define a cut-off value of tumour markers in haemodialysis patients?

PMID- 25949332
TI  - Kartagener's syndrome and polycystic kidney disease.

PMID- 25949333
TI  - A rare case of perinephric urinoma due to idiopathic retroperitoneal fibrosis.

PMID- 25949334
TI  - Long-term effects of calcium antagonists on augmentation index in hypertensive
      patients with chronic kidney diseases.

PMID- 25949335
TI  - Potentially serious medication errors with a new once-daily preparation of
      tacrolimus (AdvagrafTM).

PMID- 25949336
TI  - The 25th annual congress of the hungarian society of nephrology, szeged, 25-27
      september 2008.

PMID- 25949339
TI  - A meta-analysis of the relative doses of erythropoiesis-stimulating agents in
      patients undergoing dialysis.
AB  - Background. Erythropoiesis-stimulating agents (ESAs) such as epoetin alfa and
      beta, and darbepoetin alfa have improved the management of anaemia secondary to
      chronic kidney disease. Numerous studies have reported a dose reduction when
      patients receiving dialysis were converted from epoetin to darbepoetin alfa using
      the starting dose conversion of 200:1 as indicated on the prescribing label by
      the European Medicines Agency. The objective of this meta-analysis was to
      summarize the existing body of scientific evidence to evaluate the potential dose
      savings when comparing epoetin alfa or beta to darbepoetin alfa. Method. Medline
      and EmBase were searched to identify all published trials investigating ESA
      treatment in anaemic patients receiving dialysis and converted from epoetins to
      darbepoetin alfa. We selected prospective randomized controlled, non-randomized
      and observational studies involving patients on dialysis that compared epoetin
      and darbepoetin alfa dosing. Results. Of 573 articles identified, 9 studies met
      the eligibility criteria and were included in our analysis. The overall
      percentage dose savings attained when dialysis patients were converted from
      epoetin to darbepoetin alfa was 30% (range: 4%-44%). Greater dose savings were
      noted with intravenous administration (33%) compared with subcutaneous (27%) and
      between switch-over studies (31%) and RCTs (27%). In all studies, target
      haemoglobin levels were maintained before and after conversion. Conclusion. This
      meta-analysis demonstrates that when using an initial 200:1 conversion ratio, as
      indicated on the European label, from epoetin to darbepoetin, a subsequent
      reduction in dose was observed and an average 30% dose savings could be achieved.

PMID- 25949340
TI  - Urinanalysis (UA): a neglected but easy and inexpensive diagnostic tool.
AB  - The case history of a 75-year-old woman, who was hospitalized with the diagnosis
      of an acute erosive colitis, is presented. The patient was treated with
      hysterectomy for an endometrial cancer in 2000 and had suffered from multiple
      sclerosis for 15 years. A persistent non-productive cough with fever requested a
      pneumological consultation. Multiple small alveolar opacities and cavitating
      lesions were found at chest imaging, but no precise diagnosis was possible. Only
      3 weeks after hospitalization, we noticed that a urine analysis had been
      forgotten. This additional test clearly demonstrated a nephritic sediment and
      further analysis confirmed the diagnosis of a ANCA-positive microscopic
      polyangiitis, which promptly responded to immunosuppressive therapy. The
      necessity of a routine urine analysis in the majority of internal medicine
      patients and the possible link between small vessel vasculitis and multiple
      sclerosis are discussed. 

PMID- 25949338
TI  - A review of drug-induced hypernatraemia.
AB  - Drug-induced electrolyte abnormalities have been increasingly reported and may be
      associated with considerable morbidity and/or mortality. In clinical practice,
      hypernatraemia (serum sodium higher than 145 mmol/L) is usually of multifactorial
      aetiology and drug therapy not infrequently is disregarded as a contributing
      factor for increased serum sodium concentration. Strategies to prevent this
      adverse drug effect involve careful consideration of risk factors and clinical
      and laboratory evaluation in the course of treatment. Herein, we review evidence
      based information via PubMed and EMBASE and the relevant literature implicating
      pharmacologic treatment as an established cause of hypernatraemia and discuss its
      incidence and the underlying pathophysiologic mechanisms. 

PMID- 25949341
TI  - Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes
      (POEMS) syndrome refractory to complete serum vascular endothelial growth factor
      (VEGF) blockade: insights from sequential VEGF monitoring.
AB  - Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes
      (POEMS) syndrome is a systemic condition related to plasma cell dyscrasia.
      Increased vascular permeability is responsible for some of the hallmarks of this
      disorder that may include renal microangiopathy. Several lines of evidence
      suggest that vascular endothelial growth factor (VEGF) is central to the
      pathogenesis of POEMS syndrome. Thus, specifically targeting VEGF over-expression
      seems to be a promising treatment. Anti-VEGF therapies are yielding conflicting
      results. We report on a patient with POEMS syndrome treated with bevacizumab, an
      anti-VEGF monoclonal antibody. Sequential monitoring of serum VEGF showed
      sustained normalization of serum VEGF levels, without any beneficial effect on
      the patient's condition. Indications of this treatment should be chosen
      carefully. 

PMID- 25949342
TI  - Sacral radicular cysts in autosomal dominant polycystic kidney disease.
AB  - This is the first report of a case of sacral radicular cysts in a patient with
      autosomal dominant polycystic kidney disease (ADPKD). A 46-year-old woman with
      ADPKD was found to have bilateral sacral radicular cysts discovered incidentally
      by magnetic resonance imaging (MRI). Cysts arising from arachnoid or spinal
      meningeal sac should be considered one of the manifestations of a more widespread
      connective tissue disorder associated with ADPKD. 

PMID- 25949343
TI  - Renal infarction in patients presenting with suspected renal colic.
AB  - Acute renal infarction is a serious medical emergency. The diagnosis is often
      delayed or missed as it is not common. Hence, the exact incidence of acute renal
      infarction is not known. Failure to consider renal infarction in the initial
      differential diagnosis results in a delay in diagnosis and treatment, which in
      turn leads to permanent loss of renal function. We present two cases of acute
      kidney infarction that were initially treated as renal colic. In addition, we
      present a third case when a kidney was saved with reperfusion therapy. 

PMID- 25949344
TI  - Blue kidney in a pale patient-a case for a causal association between renal
      haemosiderosis in paroxysmal nocturnal haemoglobinuria and chronic kidney
      disease.
AB  - A 50-year-old man presented with pancytopenia and chronic renal impairment. He
      had evidence of intravascular haemolysis. The direct antiglobulin (Coomb's) test
      was negative. Paroxysmal nocturnal haemoglobinuria (PNH) was diagnosed by the Ham
      acid haemolysis test. There were no other clinical risk factors that could be
      implicated in chronic kidney disease (CKD). A renal biopsy revealed extensive
      haemosiderosis affecting proximal tubular cells and associated interstitial
      fibrosis as well as tubular atrophy. No glomerular or vascular lesions were seen.
      These findings strengthen the case for a causal relationship between renal
      haemosiderosis in PNH and CKD. 

PMID- 25949346
TI  - Kikuchi disease preceding systemic lupus erythematosus with membranous lupus
      nephritis.
AB  - Kikuchi disease (KD) is a rare form of necrotizing lymphadenitis. KD usually
      presents with cervical lymphadenopathy and fever in young women. It tends to run
      a benign course and resolve spontaneously within months. The aetiology of the
      disease is still unclear although a variety of infectious agents have been
      postulated. There is also a documented but rare association with systemic lupus
      erythematosus (SLE). We present the case of a young woman with biopsy-proven KD
      who subsequently developed SLE with biopsy-proven lupus nephritis. Nephrologists
      should be aware of KD as it may precede the development of SLE and lupus
      nephritis. 

PMID- 25949345
TI  - The combined use of sirolimus and cyclosporin in the management of refractory
      minimal change nephropathy: 'a novel use of sirolimus'.
AB  - Minimal change nephropathy (MCN) accounts for around 25% of adults presenting
      with a nephrotic syndrome. Although most patients respond to corticosteroid
      therapy, a significant number relapse frequently and may present a real
      therapeutic difficulty. We present a case of apparently refractory relapsing MCN
      that was successfully treated with a combination of sirolimus and cyclosporin,
      resulting in the longest period of steroid free remission that the patient has
      ever experienced. To our knowledge, this is the first documented use of this
      combination in this manner. 

PMID- 25949348
TI  - An unusual cause of acute renal failure in sickle cell disease.
AB  - A young female with sickle cell disease was treated for biopsy-proven IgA
      nephropathy. Serum creatinine levels resolved to normal range, but a year later,
      she presented with oedema, hypertension and acute renal failure. A repeat renal
      biopsy showed acute-on-chronic thrombotic microangiopathy (TMA). We suggest that
      circulating microparticles could be a pathophysiological link between sickle cell
      disease and the development of renal TMA. This case emphasizes the importance of
      a further biopsy for acutely declining renal function, even when a definite
      diagnosis has been made from a previous biopsy. 

PMID- 25949347
TI  - Renal biopsy in a patient with haemophilia A and cryoglobulinaemic
      membranoproliferative glomerulonephritis associated with hepatitis C virus
      infection.
AB  - A renal biopsy was performed in a 47-year-old man with haemophilia A. Thirty
      minutes after administration of an intravenous bolus of 4000 units of recombinant
      factor VIII, which increased the activity to 74-91%, a needle renal biopsy was
      successfully performed, followed by administration of 3000 units of factor VIII
      in the evening, and then the subsequent morning and evening. The patient was
      diagnosed with hepatitis C virus-associated membranoproliferative
      glomerulonephritis. Treatment with interferon, ribavirin, prednisolone and
      cyclosporine A improved the nephrotic syndrome. This is the first report of a
      successful renal biopsy in a patient with haemophilia A after factor VIII
      injection. 

PMID- 25949349
TI  - Renal involvement as the first manifestation of hypereosinophilic syndrome: a
      case report.
AB  - Idiopathic hypereosinophilic syndrome is characterized by elevated and prolonged
      blood eosinophilia along with organ system involvement and malfunction. The heart
      is the most frequently involved organ, and renal participation is extremely rare.
      Herein, we report on a case of idiopathic hypereosinophilic syndrome with renal
      involvement as the first manifestation. 

PMID- 25949350
TI  - Clarithromycin-induced acute interstitial nephritis and minimal change disease.
AB  - Drug associated acute interstitial nephritis and minimal change disease has been
      well documented but the simultaneous presentation of both is rare and has not
      been reported with clarithromycin. We describe a case of simultaneous acute
      tubulointerstitial nephritis and minimal change disease induced by
      clarithromycin. The patient had acute kidney injury, nephrotic syndrome,
      eosinophilic pneumonitis and a maculopapular skin rash. The role of steroid
      therapy in acute interstitial nephritis is controversial but is accepted as
      beneficial in minimal change nephrotic syndrome. Steroid therapy in our patient
      resulted in complete clinical resolution. 

PMID- 25949351
TI  - Polymorphisms of the glucocorticoid receptor and avascular necrosis of the
      femoral heads after treatment with corticosteroids.
AB  - A female patient developed avascular necrosis of the femoral heads after
      receiving low doses of glucocorticosteroids (GC) for 3 months. Genotyping of the
      GC receptor (GR) showed that she was heterozygous for the Bcl-1 allele and
      heterozygous for the N363S allele. Interestingly, these GR variants are both
      associated with higher sensitivity to glucocorticoids. It is not known whether
      the GR gene polymorphisms are causally related to osteonecrosis. However, the
      presence of these GR variants, as a combination present in only 1% of the normal
      Caucasian population, seems suggestive. Studies are warranted to investigate the
      importance of polymorphisms related to GC sensitivity. 

PMID- 25949352
TI  - Symptomatic uraemia from bilateral obstructive uropathy secondary to metastatic
      urinary bladder cancer showing only unilateral hydronephrosis: a case report.
AB  - Bilateral hydronephrosis is classic for supravesical obstructive uropathy causing
      uraemia with dual functioning kidneys. Recently, a patient presented with uraemia
      and metastatic urinary bladder carcinoma but only unilateral right-sided
      hydronephrosis. A right ureteral stent was placed retrograde and no further
      intervention was planned since the left kidney appeared normal, and since the
      left ureteric orifice was not visualized. We insisted on a left percutaneous
      nephrostomy which was successful with prompt urine return. A left nephrostogram
      revealed unrecognized hydroureter/hydronephrosis. Following haemodialysis, kidney
      function normalized at 3 weeks. For symptomatic uraemia from obstruction, an
      antegrade and/or a retrograde decompression must be attempted bilaterally to
      improve renal salvage. 

PMID- 25949353
TI  - Peritonitis associated with Strongyloides stercoralis in a patient undergoing
      continuous ambulatory peritoneal dialysis.
AB  - A 67-year-old male continuous ambulatory peritoneal dialysis (CAPD) patient
      presented with abdominal pain and pruritus. Strongyloides stercoralis larvae were
      seen on dialysate sediment and stool microscopic examination. Albendazole was
      given and improved the symptoms in 4 days. There was no episode of relapsing
      peritonitis after the therapy. This is the first report of S. stercoralis
      peritonitis in patients on CAPD. Strongyloides should be considered as a probable
      peritoneal pathogen in CAPD patients. 

PMID- 25949354
TI  - Worsening of hyperglycemia due to atorvastatin in a renal transplant patient.
AB  - New-onset diabetes mellitus post-renal transplantation [post-transplantation
      diabetes mellitus (PTDM)] and impaired glucose tolerance are among the most
      serious adverse metabolic disturbances of kidney transplants. We report a renal
      transplant patient whose mild post-transplant hyperglycaemia considerably
      worsened upon substituting atorvastatin for pravastatin. The patient was a 58
      years-old Caucasian man who underwent living, non-related kidney transplantation.
      The mean blood sugar level (BSL) following transplantation was 113.8 mg/dl. In an
      attempt to reduce LDL cholesterol, atorvastatin 40 mg/day was substituted for
      pravastatin. Soon after commencement of atorvastatin, polydipsia and polyuria
      appeared. Both fasting and 2-h post-prandial BSL values increased, while there
      was no change in the patient's medications, dietary habits and renal function.
      Upon reverting back to pravastatin, BSL promptly declined to the previously
      mentioned baseline values. Since PTDM is a strong independent factor of graft
      failure, cardiovascular events and mortality, physicians should be made aware of
      this possible adverse effect of atorvastatin on glucose tolerance. 

PMID- 25949355
TI  - Recurrent idiopathic membranous nephropathy in the renal allograft: successful
      treatment with the anti-CD20 monoclonal antibody rituximab.
AB  - Idiopathic membranous glomerulonephritis (IMGN) is one of the most common causes
      of nephrotic syndrome in adults. Disease progression is associated with the
      magnitude and duration of proteinuria [Reichert LJ, Koene RA, Wetzels JF.
      Prognostic factors in idiopathic membranous nephropathy. Am J Kidney Dis 1998;
      31: 1-11]. Membranous nephropathy is also one of the glomerular diseases that is
      well described to recur in the transplanted kidney [Kotanko P, Pusey CD, Levy JB.
      Recurrent glomerulonephritis following renal transplantation. Transplantation
      1997; 63: 1045]. There is no definitive therapy for primary membranous
      glomerulonephritis or recurrent disease in the graft. Cyclophosphamide plus
      steroids or cyclosporine [Cattran DC, Greenwood C, Ritchie S et al. Canadian
      Glomerulonephritis Study Group. A controlled trial of cyclosporine in patients
      with progressive membranous nephropathy. Kidney Int 1995; 47: 1130-1135] have
      been the preferred agents for the treatment of MGN involving the native kidneys.
      More recently, several reports have described the use of the anti-CD20 monoclonal
      antibody rituximab in patients with IMGN. In the current report, we present a
      patient with ESRD secondary to IMGN who developed nephrotic range proteinuria 5
      months after receiving a kidney transplant from a deceased donor. A biopsy of the
      allograft demonstrated changes compatible with recurrent membranous
      glomerulonephritis. The patient was treated with four weekly infusions of
      rituximab over a 1-month period with a significant decrease in proteinuria and an
      improvement in renal function. 

PMID- 25949356
TI  - A case of successful kidney transplantation after an extremely long-term
      maintenance haemodialysis of 38 years.
AB  - We describe herein a case of kidney transplantation after extremely long-term
      haemodialysis. A 66-year-old male received a kidney transplant from a deceased
      donor after maintenance haemodialysis for 38 years and 2 months. In spite of long
      term haemodialysis, he showed minimal calcification of the iliac vessels, and
      transplantation was carried out successfully. Other than some difficulties in
      vesical rehabilitation, his postoperative course was favourable and he was
      finally discharged from the hospital on the 84th postoperative day. On a review
      of the literature, this case might represent the longest period of haemodialysis
      ever prior to kidney transplantation in the world. 

PMID- 25949357
TI  - Hypocalcaemia and a low cardiac output after intravenous codeine phosphate
      injection: need for an additional mechanism to remove ionized calcium.

PMID- 25949358
TI  - Maltese cross-like crystals in the urinary sediment of a diabetic patient.

PMID- 25949359
TI  - Severe hyperlactaemia in the setting of alkalaemia.

PMID- 25949360
TI  - Bilateral spontaneous perirenal haemorrhage in a patient on haemodialysis.

PMID- 25949361
TI  - Mild chronic renal failure with a family history of kidney disease.

PMID- 25949362
TI  - The mineralogy and internal structure of kidney stones.

PMID- 25949363
TI  - Autosomal dominant polycystic kidney disease complicating renal ectopia and
      managed with renal transplantation.

PMID- 25949364
TI  - A kidney gone astray under pressure.

PMID- 25949365
TI  - A hidden cause of renal failure.

PMID- 25949366
TI  - Constrictive calcific pericarditis masked by haemodialysis.

PMID- 25949367
TI  - Spontaneously resolving large intrarenal artery aneurysm-a case report.

PMID- 25949368
TI  - Enoxaparin decreases serum MCP-1 concentration during haemodialysis-preliminary
      report.

PMID- 25949369
TI  - Brain renin-angiotensin system: Is it important in dialysis patients?

PMID- 25949370
TI  - The incidence of biopsy-proven glomerulonephritis in Cairo University, Egypt: a 5
      year study.

PMID- 25949371
TI  - The safety of accelerated infusion versus standard rate infusion of low-molecular
      weight iron dextran in patients with chronic kidney disease.

PMID- 25949372
TI  - Catheter-related Chryseobacterium meningosepticum bacteraemia in a haemodialysis
      patient.

PMID- 25949373
TI  - Altered mental status in a case of multiple myeloma not related to a metabolic
      cause.

PMID- 25949374
TI  - Peripheral CD19+ B cells are increased in children with active steroid-sensitive
      nephrotic syndrome.

PMID- 25949375
TI  - Professor Franciszek Kokot, born November 24th 1929 in Olesno Slaskie.

PMID- 25949376
TI  - Citrate anticoagulation for continuous renal replacement therapy (CRRT) in
      patients with acute kidney injury admitted to the intensive care unit.
AB  - Continuous forms of renal replacement therapy (CRRT) have become established as
      the treatment of choice for supporting critically ill patients with acute kidney
      injury. Typically, these patients have activation of the coagulation cascades,
      peripheral mononuclear cells and platelets, but also a reduction in natural
      anticoagulants, and are therefore prothrombotic. For continuous modes of renal
      replacement therapy to be effective, in terms of both effective solute clearance
      and also fluid removal, the extracorporeal circuits must operate continuously.
      Thus, preventing clotting in the CRRT circuit is a key goal to effective patient
      management. As these patients may also be at increased risk of bleeding, regional
      anticoagulation with citrate is increasing in popularity, particularly following
      the introduction of commercially available CRRT machines and fluids specifically
      designed for citrate anticoagulation. Although regional anticoagulation with
      citrate provides many advantages over other systemic anticoagulants, excess
      citrate may lead to both metabolic complications, ranging from acidosis to
      alkalosis and may also potentially expose patients to electrolyte disturbances
      due to hyper- and hyponatraemia and hyper- and hypocalcaemia. 

PMID- 25949377
TI  - Renal involvement in Neimann-Pick Disease.
AB  - We describe the renal biopsy findings in a 14-year-old girl with Neimann-Pick
      disease. The renal biopsy showed chronic changes involving all components of the
      parenchyma, including focal global glomerulosclerosis, tubular atrophy,
      interstitial fibrosis and vascular sclerosis. On light microscopy, significant
      findings included foamy podocytes, vacuolated tubular epithelial cells and
      collections of foam cells in the interstitium. Electron microscopy was
      confirmatory which showed myelin-like inclusions in podocytes, endothelial cells,
      tubular epithelial cells and small nerves. The findings are similar to Fabry's
      disease, except that small nerve involvement appears to be unique to Neimann Pick
      disease. 

PMID- 25949378
TI  - Nephrotic syndrome associated with immune thrombocytopenia revealing Kimura's
      disease in a non-Asian male.
AB  - We report the case of a young Caucasian man presenting with diffuse oedema and
      nephrotic syndrome. Clinical examination revealed multiple lymphadenopathies.
      Histological examination was consistent with the diagnosis of Kimura's disease. A
      renal biopsy showed focal segmental glomerulosclerosis. Immune thrombocytopenia
      and signs of humoral autoimmunity were discovered. Corticosteroid treatment
      induced remission of nephrotic syndrome but relapses occurred 12 and 18 months
      after onset of treatment while the patient was receiving 20 mg prednisone once a
      day. To our knowledge, this is the first case of Kimura's disease and nephrotic
      syndrome associated with B-cell autoreactivity. 

PMID- 25949379
TI  - Isolated microalbuminuria as the first clinical presentation of Fabry disease in
      an adult heterozygous female.
AB  - Fabry disease (FD) is a rare X-linked disorder characterized by low or absent
      activity of the lysosomal enzyme alpha-glycosidase-A that leads to progressive
      accumulation of glycosphingolipids in different organs and tissues. Clinical
      manifestations vary from classic to atypical forms characterized by one prevalent
      organ involvement, and a renal variant has been described in men but not in
      women. However, little is known about renal manifestation in females affected by
      FD. We herein report a case of a 22-year-old female with isolated and persistent
      microalbuminuria as the only sign of FD. In light of the importance of early
      recognition and treatment of FD organ damage, this case should call for future
      studies to determine how to assess organ damage, investigate the existence of a
      'renal variant' in FD female patients and determine when best to start enzyme
      replacement therapy (ERT). 

PMID- 25949380
TI  - MPO-ANCA crescentic glomerulonephritis complicated by membranous nephropathy: MPO
      demonstrated in epimembranous deposits.
AB  - An elderly woman presented with haematuria and proteinuria accompanied by
      elevated serum myeloperoxidase (MPO)-specific anti-neutrophil cytoplasmic
      antibodies (MPO-ANCA). A renal biopsy revealed mild mesangial proliferation with
      fibrocellular crescent formation and a membranous glomerular lesion.
      Immunofluorescence microscopy using FITC-labelled rabbit anti-human MPO
      antibodies revealed granular MPO deposition along the glomerular capillary walls
      (GCW) with a staining profile similar to that of glomerular IgG deposition. The
      one-year follow-up renal biopsy revealed minimal IgG and undetectable MPO
      deposition. Both MPO and MPO-ANCA might have been responsible for the IgG immune
      depositions along the GCW in this patient. 

PMID- 25949381
TI  - Acute renal failure, systemic lupus erythematosus and thrombotic microangiopathy
      following treatment with beta-interferon for multiple sclerosis: case report and
      review of the literature.
AB  - We report a man with type 1 diabetes mellitus, autoimmune hypothyroidism and a
      tentative diagnosis of multiple sclerosis. Following treatment with beta
      interferon, he developed systemic lupus erythematosus with pericarditis, pleural
      effusions, cerebral infarction associated with anti-phospholipid antibody and
      acute renal failure due to thrombotic microangiopathy. He responded well to
      immunosuppression and anticoagulation. These complications may represent the most
      severe autoimmune reaction to beta interferon reported to date. 

PMID- 25949382
TI  - Recurrent intestinal bleeding treated by double-balloon endoscopy in
      haemodialysis patients.
AB  - Gastrointestinal (GI) bleeding is a common and troublesome complication of end
      stage renal disease (ESRD). Patients often have various lesions in the small
      bowel and in either upper or lower GI tracts. Recently developed double-balloon
      endoscopy (DBE) enables observation of the entire small intestine through a
      combination of anterograde and retrograde approaches. Moreover, DBE is useful not
      only for diagnosis of small intestinal lesions; it provides a mode of treating
      the disease. This article presents patients with several small intestinal
      diseases from our facility. Their bleeding sources were identified using DBE. We
      also report two representative cases of angiodysplasia that had been diagnosed
      and treated successfully using DBE. One case particularly underscored the
      usefulness of the combination of capsule endoscopy (CE) and DBE as an electively
      diagnostic approach for patients with GI bleeding. Small intestinal bleeding is
      often observable repeatedly in a single patient, as described for case 1. In such
      circumstances, DBE can treat the lesions successfully without surgical
      procedures. In this report, ESRD patients, in whom comorbid conditions made it
      difficult to perform surgical procedures, receive great benefit from DBE. 

PMID- 25949383
TI  - Refractory uraemic pleuropericarditis treated successfully with corticosteroid
      therapy.
AB  - Uraemic pleuritis and pericarditis are frequently observed in chronic renal
      failure patients and tend to improve with continued haemodialysis. However,
      certain cases have been reported that do not respond to continued haemodialysis
      alone. A 67-year-old female on long-term haemodialysis was diagnosed with uraemic
      pleuropericarditis and treated with intensive haemodialysis and given a non
      steroidal anti-inflammatory drug to which she showed no response. We report a
      case of uraemic pleuropericarditis refractory to traditional therapy, which was
      treated successfully with corticosteroid therapy. 

PMID- 25949384
TI  - Renal clear cell carcinoma emerging in a transplanted kidney 3 years after return
      to dialysis. Case report and review of the literature.
AB  - We present a female patient with end-stage renal disease who was referred to the
      emergency department with sudden, excruciating pain over the right lower abdomen
      and flank. Radiologic evaluation following admission revealed a mass, solid in
      nature, located at the upper pole of the transplanted kidney. The patient was
      treated with empiric antibiotics and analgesics, and her symptoms subsided over
      the course of the week. Based on the clinical course and radiological findings, a
      self-limiting, spontaneous haemorrhage was thought to be the cause of the
      patient's symptoms. Nevertheless, background malignancy could not be ruled out.
      Therefore, an interval, elective graft nephrectomy was scheduled. Pathology
      confirmed the diagnosis of renal clear cell carcinoma. 

PMID- 25949385
TI  - Hereditary nephrogenic diabetes insipidus: a major conundrum during labour and
      delivery.

PMID- 25949386
TI  - Star fruit: simultaneous neurotoxic and nephrotoxic effects in people with
      previously normal renal function.

PMID- 25949387
TI  - C-peptide and combined kidney-pancreas transplantation.

PMID- 25949388
TI  - 'Stone'-blindness.

PMID- 25949389
TI  - The 'double dutch' Doppler.

PMID- 25949390
TI  - Secondary hyperoxaluria and urinary crystal casts after intestinal resection.

PMID- 25949391
TI  - Haematuria and hydronephrosis caused by Castleman's disease.

PMID- 25949392
TI  - Calcification of the liver in a patient on renal replacement therapy diagnosed
      with systemic calciphylaxis.

PMID- 25949393
TI  - Occult hepatitis B virus infection in a Sicilian chronic dialysis population.

PMID- 25949394
TI  - Thalidomide-induced heart block in a dialysis patient.

PMID- 25949395
TI  - Adherence to guideline recommendations for infection prophylaxis in peritoneal
      dialysis patients.

PMID- 25949396
TI  - A single-dose vancomycin application after standard protocol in peritoneal
      dialysis patients with recurrent peritonitis.

PMID- 25949397
TI  - Biocompatibility of peritoneal dialysis solutions determined by genomics of human
      leucocytes: a cross-over study.

PMID- 25949398
TI  - Crescentic glomerulonephritis in a patient with advanced lung cancer during
      erlotinib therapy.

PMID- 25949399
TI  - Promoting scientific collaboration and education in cardiovascular-renal
      medicine: EURECAM: An ERA-EDTA-based working group.

PMID- 25949400
TI  - Specific nutritional problems in acute kidney injury, treated with non-dialysis
      and dialytic modalities.
AB  - Patients who develop AKI, especially in the intensive care unit (ICU), are at
      risk of protein-energy malnutrition, which is a major negative prognostic factor
      in this clinical condition. Despite the lack of evidence from controlled trials
      of its effect on outcome, nutritional support by the enteral (preferentially)
      and/or parenteral route appears clinically indicated in most cases of ICU
      acquired AKI, independently of the actual nutritional status of the patient, in
      order to prevent deterioration in the nutritional state with all its known
      complications. Extrapolating from data in other conditions, it seems
      intrinsically unlikely that starvation of a catabolic patient is more beneficial
      than appropriate nutritional support by an expert team with the skills to avoid
      the potential complications of the enteral and parenteral nutrition
      methodologies. By the same token, it is ethically impossible to conduct a trial
      in which the control group undergoes prolonged starvation. The primary goals of
      nutritional support in AKI, which represents a well-known inflammatory and pro
      oxidative condition, are the same as those for other critically ill patients with
      normal renal function, i.e. to ensure the delivery of adequate nutrition, to
      prevent protein-energy wasting with its attendant metabolic complications, to
      promote wound healing and tissue repair, to support immune system function, to
      accelerate recovery and to reduce mortality. Patients with AKI on RRT should
      receive a basic intake of at least 1.5 g/kg/day of protein with an additional 0.2
      g/kg/day to compensate for amino acid/protein loss during RRT, especially when
      daily treatments and/or high efficiecy modalities are used. Energy intake should
      consist of no more than 30 kcal non-protein calories or 1.3 * BEE (Basal Energy
      Expenditure) calculated by the Harris-Benedict equation, with ~30-35% from lipid,
      as lipid emulsions. For nutritional support, the enteral route is preferred,
      although it often needs to be supplemented through the parenteral route in order
      to meet nutritional requirements. 

PMID- 25949402
TI  - The EVEREST study: an international collaboration.
AB  - Rates of initiation of renal replacement therapy (RRT), use of home modalities of
      treatment and patient outcomes vary considerably between countries. This paper
      reports the methods and baseline characteristics of countries participating in
      the EVEREST study (n = 46), a global collaboration examining the association
      between medical and non-medical factors and RRT incidence, modality mix and
      survival. Numbers of incident and prevalent patients were collected for current
      (2003-05) and historic (1983-85, 1988-90, 1993-95 and 1998-2000) periods
      stratified, where available, by age, gender, treatment modality and cause of end
      stage renal disease (diabetic versus non-diabetic). General population age and
      health indicators and national-level macroeconomic data were collected from
      secondary data sources. National experts provided primary data on renal service
      funding, resources and organization. The median (inter quartile range) RRT
      incidence per million of the population (pmp) was 130 pmp (102-167 pmp). The
      general population life expectancy at 60 was 22.1 years (19.7-23.1 years) and
      6.9% had diabetes mellitus (5.4-9.0%). Healthcare spending as a percentage of
      gross domestic product was 8.1% (5.6-9.3%). Countries averaged nine dialysis
      facilities pmp (4-12 pmp), with 69.0% (43.9-99.0%) owned by the public or private
      not-for-profit sector. The number of nephrologists ranged from 0.5 to 48 pmp
      (median 12 pmp). The heterogeneity of EVEREST countries will enable modelling to
      examine the independent association between medical and non-medical factors on
      RRT epidemiology. 

PMID- 25949401
TI  - Late referral of patients with end-stage renal disease: an in-depth review and
      suggestions for further actions.
AB  - Late referral of patients with chronic kidney disease (CKD) is a known problem
      and a major challenge for practising nephrologists since decades. In this review
      we report about the reasons for late referral, its epidemiology and socioeconomic
      impact and the medical particularities of late referred patients. We furthermore
      highlight on the efforts which have been undertaken so far to avoid late referral
      and should be undertaken in future to face the ever growing numbers of chronic
      kidney disease patients. 

PMID- 25949403
TI  - Turbid white urine.
AB  - Turbid white urine 'albinuria' is defined as a urine discoloration described as
      milky or cloudy. One of the most frequent causes of turbid white urine is
      chyluria complicating filariasis (Table 1). The extant causes of albinuria are
      non parasitic and rare. Amongst their aetiologies stand excessive mineral
      sediment excretion such as calciuria and phosphaturia, massive pyuria and fungal
      infections, and rarely congenital malformations of the lymphatic vessels.
      Malingering is also possible, in patients adding milk to their urine. We observed
      a case of albinuria in which the diagnostic work up led to diagnosing an
      exceptional cause of chyluria in a patient living in a region of Colombia where
      filariasis is not endemic. 

PMID- 25949404
TI  - The effect of spontaneous twin pregnancy on renal transplant function and
      haemodynamics.
AB  - Spontaneous twin pregnancy is rare in renal transplant recipients, and confers a
      significant risk, in terms of both transplant dysfunction and fetal
      complications. Physiological changes in renal haemodynamics may assist in
      predicting a favourable outcome, but have not been previously reported in these
      circumstances. We present a case of a successful outcome for both mother and
      babies, and detail the effects of the pregnancy on transplant function and
      haemodynamics within the transplant kidney. Without beneficial circumstances,
      twin pregnancy may be a high risk in renal transplant recipients and may lead to
      a poor outcome for both transplant and fetuses. 

PMID- 25949406
TI  - Adult-onset Still's disease associated with collapsing glomerulopathy.
AB  - A young woman of African descent presented with fevers, arthralgia,
      lymphadenopathy and a skin rash. Modest proteinuria was also noted. The clinical
      picture suggested an acute HIV sero-conversion illness, and a renal biopsy showed
      a collapsing glomerulopathy compatible with that diagnosis. However, HIV serology
      proved persistently negative and a diagnosis of Adult Still's disease was
      subsequently made (by Yamaguchi criteria). Following steroid treatment, the
      patient's fever abated and her inflammatory markers returned to normal.
      Collapsing glomerulopathy is a rare but important complication of Adult Still's
      disease. Immunosuppressive treatment may be effective in improving renal outcome.

PMID- 25949405
TI  - Nephrotic syndrome and renal failure as an unusual presentation of solid tumour.
AB  - Glomerular diseases may occur as primary manifestation of cancer, especially in
      patients older than 60 years. Among glomerulopathies, membranous nephropathy is
      preferentially associated with respiratory and gastrointestinal tract
      adenocarcinomas, whereas minimal change disease is most often seen in
      haematological malignancies. Though breast cancer is one of the most frequent
      malignancies in women, paraneoplastic glomerular disease is rarely observed. We
      describe the case of a 79-year-old female patient who presented with nephrotic
      syndrome and renal failure. Breast cancer was found. Pathological studies of
      kidney and breast biopsy revealed a minimal change disease and an infiltrating
      ductal carcinoma, respectively. 

PMID- 25949407
TI  - Fibrillary glomerulonephritis with prevalent IgA deposition associated with
      undifferentiated connective tissue disease: A case report.
AB  - We described a 41-year-old female patient, who presented with proteinuria
      occurring 5 years after the onset of an undifferentiated connective tissue
      disease (UCTD). At renal biopsy, a pattern of focal necrotizing
      glomerulonephritis with mesangial and parietal deposition of the IgA, C3 and K
      chains was observed. Electron microscopy showed organized fibrillary deposits in
      mesangial, subendothelial, intramembranous and subepithelial sites. Fibrils were
      randomly arranged, had no hollow core and had a diameter ranging between 10 and
      23 nm. This case showed a rare combination of fibrillary glomerulonephritis and
      prevalent IgA deposition, in the clinical context of UCTD. 

PMID- 25949408
TI  - Ectopic ossification in the cranial dura mater in dialysis patients with
      secondary hyperparathyroidism.
AB  - We report the case of a 69-year-old woman with secondary hyperparathyroidism who
      underwent maintenance haemodialysis therapy for 17 years and who presented with
      severe dural calcification and right subdural haematoma. Her dura mater displayed
      a rock barnacle-like appearance, and cerebral superficial arteries adhered to the
      sclerotic lesions. On the microscopic observation, calcified tissue with a clear
      lamellar structure and osteopontin immunoreactivity was observed. Tartrate
      resistant acid phosphatase immunoreactive polynucleated giant cells infiltrated
      around the tissue. Such morphological properties are specific to the calcified
      tissue formed through a bone formation-like mechanism that is often observed in
      arterial media in patients with chronic kidney disease. 

PMID- 25949409
TI  - The importance of prevention of calciphylaxis in patients who are at risk and the
      potential fallibility of calcimimetics in the treatment of calciphylaxis for
      patients with secondary hyperparathyroidism.
AB  - A 43-year-old African American with end-stage renal disease (ESRD) associated
      with membranous nephropathy and a previously failed renal transplant had received
      cinacalcet to treat his secondary hyperparathyroidism. Serum calcium and
      phosphorus levels remained within normal limits, and serum parathyroid levels had
      dropped significantly following treatment initiation. However, within 7 months,
      the patient experienced extensive necrotic bilateral medial thigh ulcers. These
      were biopsied and found to be a result of calciphylaxis. The patient ultimately
      required an urgent subtotal parathyroidectomy and recovered well with completely
      healed ulcers. 

PMID- 25949410
TI  - Marked increase in bone formation markers after cinacalcet treatment by
      mechanisms distinct from hungry bone syndrome in a haemodialysis patient.
AB  - A 59-year-old female who was on dialysis due to diabetic nephropathy was referred
      to our hospital for severe hyperparathyroidism refractory to intravenous vitamin
      D receptor activator treatment. With subsequent cinacalcet hydrochloride
      treatment, parathyroid hormone (PTH) levels were only slightly suppressed.
      However, progressive increases were observed in serum alkaline phosphatase (ALP)
      and bone-specific alkaline phosphatase (BAP) levels with mild hypocalcaemia. A
      bone biopsy, obtained immediately before surgical parathyroidectomy after 3
      months of cinacalcet treatment, revealed no disappearance of osteoclasts. These
      data suggest that cinacalcet hydrochloride treatment may induce a marked
      promotion of bone formation by mechanisms distinct from hungry bone syndrome that
      usually develops after parathyroidectomy. 

PMID- 25949411
TI  - A case of bilateral renal arterial thrombosis associated with
      cryocrystalglobulinaemia.
AB  - Cryocrystalglobulinaemia is an extremely rare complication of monoclonal
      gammopathy. Its presentation has features of both type I and II
      cryoglobulinaemia. Although peripheral and digital ischaemia is common, visceral
      ischaemia is rare. When it does occur, it is usually associated with multiple
      myeloma and has an extremely poor prognosis. We present a case of bilateral renal
      artery thrombosis associated with cryocrystalglobulinaemia in a patient without
      myeloma. More unusual, the cryocrystal protein in this case was associated with
      fibrinogen, which may have led to increased propensity towards thrombosis.
      Although the patient was unable to recover his kidney function, he remained alive
      on dialysis 2 years after the incident. The patient did not have any further
      ischaemic event despite no definitive therapy. This case represents an unusual
      presentation for this rare disease. 

PMID- 25949412
TI  - Hypocomplementaemic immune complex tubulointerstitial nephritis.
AB  - We report a rare cause of rapidly progressive renal failure associated with low
      complement, positive ANA but negative anti DS-DNA. A renal biopsy demonstrated
      tubulointerstitial nephritis with positive immunoglobulin staining involving the
      interstitium and tubular basement membrane but glomerular sparing. A review of
      the literature and differential diagnosis are discussed. 

PMID- 25949413
TI  - A pilot in distress.

PMID- 25949414
TI  - Hypokalaemia and the thyroid-is there a link?

PMID- 25949415
TI  - Post-renal transplant calciphylaxis: treatment of hyperparathyroidism by
      percutaneous ethanol injection therapy and parathyroidectomy.

PMID- 25949416
TI  - Tuberculous osteomyelitis of the foot in a haemodialysis patient.

PMID- 25949417
TI  - Adrenal insufficiency in a haemodialysis patient.

PMID- 25949418
TI  - Successful treatment of spontaneous kidney graft decapsulation 18 years after
      renal transplantation: a case report.

PMID- 25949420
TI  - Reversible proteinuria after adalimumab discontinuation in a patient with Crohn's
      disease.

PMID- 25949419
TI  - IgG4(+)MOLPS associated with inflammatory abdominal aortic aneurysm, interstitial
      pneumonia and interstitial nephritis.

PMID- 25949421
TI  - Lacking evidence for calcium-binding protein fetuin-A to be linked with chronic
      kidney disease-related pruritus (CKD-rP).

PMID- 25949422
TI  - Bone morphogenic protein-7: a new prognostic marker for acute kidney injury?

PMID- 25949423
TI  - Turbid urine and beef-eating rabbits: Claude Bernard (1813-78)-a founder of
      modern physiology.

PMID- 25949425
TI  - Anaphylaxis with elevated serum tryptase after administration of intravenous
      ferumoxytol.
AB  - Ferumoxytol is a newly approved preparation of intravenous iron with a modified
      dextran shell that is thought to confer upon it a low immunogenic potential.
      Serious adverse reactions have been very uncommon in clinical studies, but these
      studies excluded patients with prior adverse reactions to other preparations of
      intravenous iron. Furthermore, the reactions were classified clinically. We
      report on a patient with a history of hypersensitivity to iron dextran who
      experienced an anaphylactic reaction after receiving ferumoxytol. Laboratory
      testing revealed an elevated serum tryptase level, confirming mast cell
      activation. This is the first laboratory-proven case of anaphylaxis related to
      ferumoxytol. 

PMID- 25949424
TI  - Acute kidney injury requiring dialysis: a very unusual presentation of non
      Hodgkin's lymphoma.
AB  - Acute kidney injury due to lymphomatous infiltration of the kidneys is uncommon,
      and it is rarely the initial manifestation of the lymphoma. Here, we present a
      case of lymphomatous infiltration of the kidneys resulting in acute kidney injury
      requiring dialysis, as the initial presentation of non-Hodgkin's lymphoma. Renal
      biopsy established the diagnosis, and renal function completely recovered after
      chemotherapy. 

PMID- 25949426
TI  - Nurofen Plus toxicity-what should nephrologists be alert to? Rare complications
      of an increasingly misused medication.
AB  - We report the staggered clinical course of a young Caucasian female who suffered
      rare deleterious effects of Nurofen Plus misuse with a near fatal outcome.
      Several life-threatening events intervened before the underlying problem of
      serious dependency was identified. Effects on renal tubular acidification and
      bone marrow function as well as the commoner complications of acute kidney injury
      and peptic ulceration are described. In addition, this is the first case report
      in which the syndrome of reversible posterior leucoencephalopathy is linked to
      analgesic misuse, occurring after recovery of renal function. Recommendations for
      restricting availability of codeine-based analgesics are made. 

PMID- 25949427
TI  - The development of membranous lupus nephritis during treatment with mycophenolate
      mofetil for proliferative renal disease.
AB  - The transformation of lupus nephritis from one histologic pattern to another is
      well described. We report a case of a patient who initially presented with
      diffuse proliferative glomerulonephritis and was treated with prednisone and
      mycophenolate mofetil (MMF). She initially responded well to therapy, but later
      developed high-grade proteinuria while still on MMF and low-dose steroids. A
      repeat biopsy performed after the increase in proteinuria demonstrated that she
      had focal proliferative disease but that she had also developed membranous lupus
      nephritis. Our case is unique in that we report a patient who developed
      membranous lupus nephritis while receiving MMF. 

PMID- 25949428
TI  - Glomerulocystic disease.
AB  - Glomerulocystic disease is a rare cause of cystic kidney diseases and can occur
      at any age. It is characterized by cystic dilatation of the Bowman's capsule and
      normal tubules, and needs to be differentiated from other cystic renal diseases.
      It commonly presents as renal failure. We present a case of a 52-year-old female,
      with renal failure who was subsequently found to have glomerulocystic disease on
      renal biopsy. 

PMID- 25949429
TI  - A CF patient with progressive proteinuric renal disease: a CF-specific nodular
      glomerulosclerosis?
AB  - Cystic fibrosis (CF) is a multisystemic disease but without a classical disease
      specific renal phenotype. A 32-year-old male patient with CF
      (DeltaF508/DeltaF508) presented with a nephrotic syndrome. Renal biopsy revealed
      nodular glomerulosclerosis (NGS) occurring in the absence of diabetes mellitus,
      amyloidosis and any other known common cause of NGS. He had a progressive decline
      in estimated glomerular filtration rate (eGFR) to chronic kidney disease stage V
      (eGFR <15 mL/min/1.73 m(2)) over a 3-year period despite optimal medical
      management. This is the fourth reported case of NGS in a patient with CF without
      diabetes and is the first to originate from a European country. This case
      supports the concept of a CF-related NGS. 

PMID- 25949430
TI  - Steroid-responsive nephrotic syndrome in a patient with proliferative
      glomerulonephritis with monoclonal IgG deposits with pure mesangial proliferative
      features.
AB  - A 78-year-old woman developed acute-onset nephrotic syndrome. A renal biopsy
      showed mild mesangial proliferative glomerulonephritis. Immunofluorescence
      studies revealed granular IgG3- lambda deposits within the mesangial area and
      along the glomerular capillary walls. Electron microscopy showed mesangial and
      subendothelial granular electron-dense deposits. The pattern of deposition was
      predominantly mesangial. Serum or urine monoclonal proteins were not detected.
      Middle-dose steroid therapy induced a rapid remission of nephrotic syndrome. We
      consider that this is the first case of steroid-responsive nephrotic syndrome due
      to an extremely rare glomerular disease, proliferative glomerulonephritis with
      monoclonal IgG deposits associated with pure mesangial proliferative features. 

PMID- 25949431
TI  - An unusual renal manifestation of chronic HBV infection.
AB  - Hepatitis B viral infection is usually a self-limiting disease in immunocompetent
      individuals. Chronic infection can be seen in up to 5% of infected patients.
      Renal manifestations of chronic HBV infection are usually glomerular. We describe
      here an uncommon presentation of a patient with chronic HBV infection with very
      high viral load and rapidly progressive renal failure. Renal biopsy showed
      features of tubulointerstitial nephritis and tubular epithelial inclusion bodies
      suggestive of HBV infection. Entecavir treatment slowed down the progression of
      his renal disease. Tubulointerstitial nephritis should be considered as a part of
      the differential diagnosis in patients with HBV infection. Early antiviral
      treatment may halt the progression of renal disease. 

PMID- 25949432
TI  - Delayed spontaneous resolution of nephrotic syndrome in a patient with hepatitis
      C virus-associated membranoproliferative glomerulonephritis.
AB  - Treatment with antiviral and/or immunosuppressive therapy is considered the
      standard care in patients with hepatitis C virus (HCV)-associated
      membranoproliferative glomerulonephritis (MPGN). However, even with an adequate
      therapy, a favourable response is not always guaranteed. In patients with HCV
      associated MPGN, a delayed spontaneous remission of nephrotic syndrome is rare.
      We present here one such case. Our patient refused antiviral (and
      immunosuppressive) therapy throughout the course of his illness and was thus
      managed symptomatically. More than 8 months after presentation, an unexpected
      gradual resolution of his nephrotic syndrome was noted. The urine
      protein/creatinine ratio decreased from ~16 000 mg/g of creatinine on
      presentation to 500 mg/g of creatinine in the 12th month. This was however not
      accompanied by resolution of HCV or cryoglobulinaemic activity. Our case
      demonstrates the possibility of a delayed spontaneous remission occurring in this
      disease. This must be considered when weighing treatment options in such
      patients. 

PMID- 25949433
TI  - Hyperparathyroidism with hypercalcaemia in chronic kidney disease: primary or
      tertiary?
AB  - Objective . This study aims to highlight the challenges in the diagnosis of
      hyperparathyroidism (HPT) in patients with advanced chronic kidney disease (CKD).
      Methods . In this report, we describe a middle-aged Filipino gentleman with
      underlying CKD who presented with intractable nausea, vomiting, severe and
      medically refractory hypercalcaemia and parathyroid hormone (PTH) concentrations
      in excess of 2400 pg/mL. The underlying pathophysiology as well as the
      aetiologies and current relevant literature are discussed. We also suggest an
      appropriate diagnostic approach to identify and promptly treat patients with CKD,
      HPT and hypercalcaemia. Results . Evaluation confirmed the presence of a large
      parathyroid adenoma; HPT and hypercalcaemia resolved rapidly following resection.
      Conclusion . This case report is remarkable for its severe hypercalcaemia
      requiring haemodialysis, large adenoma size, acute-on-chronic kidney injury and
      markedly elevated PTH concentration in association with primary HPT in CKD. 

PMID- 25949434
TI  - Pathological changes in chronic eosinophilic peritonitis in peritoneal dialysis
      patient.
AB  - We report the pathological findings of the peritoneum in a patient with chronic
      eosinophilic peritonitis. Peripheral blood eosinophilia was confirmed before
      insertion of Tenckhoff catheter. Eosinophilic peritonitis continued from the
      second day after initiation of peritoneal dialysis for 18 months. Pathological
      findings showed numerous eosinophils in peritoneal blood vessels. Mast cells were
      also detected in the peritoneum, while neoangiogenesis was not prominent. The
      highly permeable state of the peritoneal membrane may be due to inflammatory
      mediators, such as tryptase. Mast cells may be involved in high peritoneal
      permeability in such patients. 

PMID- 25949435
TI  - Spontaneous gall bladder haemorrhage in a renal dialysis patient following
      haemodialysis with tinzaparin.
AB  - Spontaneous gall bladder haemorrhage is a rare and serious occurrence with a few
      cases reported in the literature in haemodialysis patients. This report describes
      this complication following dialysis with a low-molecular-weight heparin (LMWH)
      tinzaparin. This patient presented with acute right upper quadrant pain and
      intermittent haematemesis following 4 hours of haemodialysis. Despite being well
      established on dialysis, LMWH had only been used once previously. There was no
      history of trauma or pre-existing gall bladder pathology and no clinical or
      biochemical evidence of inflammation or infection. Computed tomography (CT) scan
      revealed an extensive gall bladder haemorrhage. The patient was treated
      conservatively with analgesia, and blood transfusion and symptoms settled without
      intervention. This case report highlights a rare site of bleeding following LMWH
      use in a haemodialysis patient. 

PMID- 25949436
TI  - An unusual case of CMV cutaneous ulcers in a renal transplant recipient and
      review of literature.
AB  - Cytomegalovirus (CMV) infection involving the skin is rare. We present a case of
      a renal transplant recipient who developed fever and axillary, scrotal and penile
      skin ulcers after renal transplantation. The skin ulcers did not heal with
      antibiotics. The skin biopsy revealed CMV inclusion bodies, CMV antigen on
      immunohistochemistry and high CMV DNA copies. The patient was diagnosed with CMV
      cutaneous ulcers. The skin ulcers healed after treatment with intravenous
      ganciclovir and oral valganciclovir. The diagnosis of CMV disease should be
      considered in the febrile immunosuppressed patient with skin ulcers. The biopsy
      of the cutaneous lesions may provide the diagnostic clue in such patients. 

PMID- 25949437
TI  - New influenza A (H1N1/09) in three renal transplant patients.
AB  - The pandemic new influenza A (H1N1/09) virus may be especially threatening for
      immunosuppressed renal transplant patients as they are at increased risk for
      complications, prolonged infection and mortality. This is the first case report
      of renal transplant patients with PCR-confirmed H1N1 respiratory tract infection.
      They showed a surprisingly mild clinical course despite respiratory fungal or
      viral co-infections in two cases. Treatment with oseltamivir in standard dosage
      was immediately started after diagnosis and proved to be rapidly beneficial with
      respect to clinical outcome and virus shedding without deteriorating renal
      transplant function. 

PMID- 25949438
TI  - An unusual cause of acute renal failure: hypothyroidism.

PMID- 25949439
TI  - Adenovirus nephritis and obstructive uropathy in a renal transplant recipient:
      case report and literature review.
AB  - We report an unusual case of adenoviral nephritis in a 45-year-old woman who
      presented with fever, gross haematuria, acute kidney injury and obstructive
      uropathy 17 months following renal transplantation. Adenoviral nephritis was
      confirmed with immunohistochemistry. We identified 10 other published cases of
      adenoviral nephritis proven by immunohistochemistry. Obstructive uropathy has
      been reported only once before in a renal transplant recipient with adenoviral
      nephritis. Contrary to other reports, this case series shows that renal function
      may not always recover to baseline following the acute adenoviral disease.
      Adenoviral nephritis should be considered in the renal transplant patient with
      fever, haematuria, acute kidney injury and hydronephrosis in both the early and
      late post-transplant periods. 

PMID- 25949440
TI  - Hereditary and acquired thrombophilic disorders complicating vascular access in
      haemodialysis: O. Sarkar et al.

PMID- 25949441
TI  - Renal allograft granulomas in the early post-transplant period.

PMID- 25949442
TI  - What is the risk that I will transmit nephrotic syndrome to my children, Doctor?

PMID- 25949443
TI  - Post-ESWL fragments as core of new kidney stones.

PMID- 25949444
TI  - Bone scinitigraphy in rhabdomyolysis associated with carnitine palmitoyl
      transferase deficiency.

PMID- 25949445
TI  - Flank bruits due to giant renal arteriovenous malformation.

PMID- 25949446
TI  - Giant emphysematous cystitis in a patient with diabetic uraemia.

PMID- 25949447
TI  - Angiogenesis and cellularity in encapsulating peritoneal sclerosis.

PMID- 25949448
TI  - Bilateral renal vein thrombosis secondary to methylene tetrahydrofolate reductase
      mutation: a rare case.

PMID- 25949449
TI  - A growing transplanted kidney.

PMID- 25949450
TI  - The spot urine protein/creatinine ratio is a simple, rapid and inexpensive method
      for monitoring patients with light-chain multiple myeloma.

PMID- 25949451
TI  - Doxycycline for haematopoietic stem cell transplantation-related thrombotic
      microangiopathy.

PMID- 25949452
TI  - Additional antibody suppression from rituximab added to conventional therapy in
      severe, refractory anti-GBM nephritis.

PMID- 25949453
TI  - Interaction between tacrolimus and clindamycin.

PMID- 25949454
TI  - Should we recommend precautions during a hantavirus endemic?

PMID- 25949455
TI  - An atypical pneumonia in a renal transplant patient.

PMID- 25949456
TI  - High risk of chronic kidney disease: results of the screening during World Kidney
      Day 2010.

PMID- 25949457
TI  - Anti-angiogenic assay assists fetal extraction decision in a case of pre
      eclampsia suspicion?

PMID- 25949458
TI  - Pleiotropic effects of vitamin D in an early stage of chronic kidney disease
      effect on insulin resistance.

PMID- 25949459
TI  - Individualizing anaemia therapy.
AB  - Individualized strategies for managing renal anaemia with erythropoiesis
      stimulating agents (ESAs) need to be advanced. Recent outcomes from clinical
      studies prompted a narrowing of the guideline-recommended haemoglobin target (11
      12 g/dL) due to increased mortality and morbidity when targeting higher
      haemoglobin concentrations. Maintaining a narrow target is a clinical challenge,
      as haemoglobin concentration tends to fluctuate. The goal of individualized
      treatment is to achieve the haemoglobin target at the lowest ESA dose while
      avoiding significant fluctuations in haemoglobin concentrations and persistently
      low or high concentrations. This may require changes to the ESA dose and dosing
      frequency over the course of treatment. 

PMID- 25949461
TI  - Symptomatic hyponatremia during glomerular filtration rate testing.
AB  - Hyponatremia affects nearly one in five of all hospitalized patients. Severe
      hyponatremia is associated with significant morbidity and mortality, and is
      therefore important to recognize. Prior reports have linked duloxetine with
      hyponatremia, but it is uncommon. In this case report, we describe a research
      subject taking duloxetine who developed severe symptomatic hyponatremia during
      glomerular filtration rate testing despite having undergone such testing
      uneventfully in the past. 

PMID- 25949462
TI  - A de novo novel missense mutation in AVPR2 with severe nephrogenic diabetes
      insipidus.
AB  - We describe a paediatric case of nephrogenic diabetes insipidus (NDI) with a
      novel mutation in the arginine vasopressin receptor 2 gene (AVPR2) in the absence
      of a family history of congenital polyuria. The patient, a 5-month-old Caucasian
      boy, had failure to thrive and hypernatraemia. On admission to hospital, he had a
      plasma sodium of 171 mEq/L with a concomittant urine osmolality of 131 mOsm/kg.
      Molecular genetic analysis demonstrated that the patient had an AVPR2 mutation
      (c.861C > G) resulting in a substitution of tryptophan for serine at amino acid
      position 167 (p.Ser167Trp). His mother was heterozygous for the same Ser167Trp
      mutation which was found to be de novo from the DNA analysis of the maternal
      grandparents. 

PMID- 25949460
TI  - Novel solid phase-based ELISA assays contribute to an improved detection of anti
      HLA antibodies and to an increased reliability of pre- and post-transplant
      crossmatching.
AB  - Antibodies directed against HLA antigens of a given organ donor represent the
      dominating reason for hyper-acute or acute allograft rejections. In order to
      select recipients without donor-specific antibodies, a standard crossmatch (CM)
      procedure, the complement-dependent cytotoxicity assay (CDC), was developed. This
      functional assay strongly depends on the availability of isolated vital
      lymphocytes of a given donor. However, the requirements of the donor's material
      may often not be fulfilled, so that the detection of the antibodies directed
      against HLA molecules is either impaired or becomes completely impossible. To
      circumvent the disadvantages of the CDC procedure, enzyme-linked immunosorbent
      assay (ELISA)-based and other solid phase-based ELISA-related techniques have
      been designed to reliably detect anti-HLA antibodies in recipients. Due to the
      obvious advantages of these novel technologies, when compared with the classical
      CDC assay, there is an urgent need to implement them as complementary methods or
      even as a substitution for the conventional CDC crossmatch that is currently
      being applied by all tissue typing laboratories. 

PMID- 25949463
TI  - A novel mutation in NPHS2 causing nephrotic syndrome in a Saudi Arabian family.
AB  - We report a consanguineous family from Saudi Arabia with three affected children
      presenting with infantile nephrotic syndrome. In order to provide a molecular
      diagnosis, a genome-wide SNP analysis of the affected patients was performed. We
      identified a region of homozygosity on chromosome 1, containing the NPHS2 gene.
      Direct sequencing, by exon PCR, of NPHS2 identified a homozygous nucleotide
      change 385C > T within exon 3 in the three affected children, leading to a
      premature stop codon (Q129X). This homozygous truncating mutation in NPHS2 is
      novel and was associated with a severe clinical phenotype. Additional mutations
      in related genes NPHS1, PLCE1 and NEPH1 were not identified, excluding tri
      allelism within these genes in this family. 

PMID- 25949464
TI  - Severe peri-renal sepsis in established renal failure masquerading as an acute
      abdominal catastrophe.
AB  - Severe worsening lactic acidosis in an elderly patient following an episode of
      atrial fibrillation, who is not haemodynamically compromised, usually indicates
      an intra-abdominal vascular catastrophe. We describe a unique case of severe peri
      renal sepsis in a patient with long-standing dialysis-dependent chronic kidney
      disease unrelated to urolithiasis that masqueraded as an acute abdominal
      condition requiring emergency laparotomy and nephrectomy. 

PMID- 25949465
TI  - Iatrogenic nephrocalcinosis with acute renal failure: an underestimated
      complication after parathyroidectomy?
AB  - Hypocalcaemia often occurs in patients after parathyroidectomy (PTX) due to
      hypoparathyroidism and/or hungry bone syndrome. To avoid hypocalcaemia, patients
      are substituted with large doses of calcium and vitamin D. Here, we present four
      patients, who developed acute renal failure with hypercalcaemia and/or
      histologically confirmed nephrocalcinosis after PTX due to oversubstitution with
      vitamin D analogues and calcium. As a consequence, serum and urinary calcium
      should be closely monitored after PTX, and calcium and vitamin D substitution
      should be continuously adapted to avoid not only hypocalcaemia but also
      nephrocalcinosis and hypercalcaemic renal failure. 

PMID- 25949466
TI  - Inadequate drug prescription and the rise in drug-induced acute
      tubulointerstitial nephritis incidence.
AB  - Drugs are a frequent cause of acute tubulointerstitial nephritis (ATIN).
      Antibiotics, non-steroidal anti-inflammatory drugs and recently proton pump
      inhibitors stand among the most commonly responsible ones. However, their
      respective responsibility is not well known. This study reports 33 cases of drug
      induced ATIN (DI-ATIN), the most frequent ones being metamizole and omeprazole.
      Clinicians often fail to diagnose DI-ATIN because its signs and symptoms are non
      specific and differ from the now classic form observed with methicillin.
      Furthermore, drugs causing ATIN are too often prescribed unnecessarily. This
      study shows that in more than one-fifth of our cases, ATIN complicated
      prescription of a drug that was not justified by an adequate clinical indication.
      The consequences were noxious for the patients and costly in terms of public
      health expenses. 

PMID- 25949467
TI  - Non-Randall proliferative glomerulonephritis with humps and monotypic IgG
      deposits in primary Sjogren's syndrome: a first case report.
AB  - Renal involvement is frequent in patients suffering from primary Sjogren's
      syndrome (pSS). Tubulointerstitial infiltration is the most common renal lesion,
      while glomerular involvement is rare. We report the case of a 50-year-old woman
      with pSS who developed renal failure due to an unusual proliferative
      glomerulonephritis with humps and monotypic IgG1-kappa deposits. Searches for
      cryoglobulinaemia, anti-double-stranded DNA and anti-neutrophil cytoplasmic
      antibodies were negative. Serum protein electrophoresis and immunofixation
      revealed no monoclonal immunoglobulin. Extensive work-up excluded associated
      infectious, collagen or lymphoproliferative disease. This case adds to the
      spectrum of pSS-related glomerular disease which is reviewed in depth. 

PMID- 25949468
TI  - Collapsing glomerulopathy after hepatitis C pegylated interferon treatment.
      Recovery of renal function with high-dose steroid treatment.
AB  - A patient who developed oliguric acute renal failure and nephrotic syndrome
      within 2 weeks after finishing interferon and ribavirin treatment is reported. At
      presentation, HCV PCR was negative, and no immunological laboratory test was
      found altered. A renal biopsy showed collapsing glomerulopathy, and the patient
      received supportive haemodialysis and high-dose steroids. Twelve days after
      steroid treatment, renal function started to recover. After 18 weeks, normal
      renal function and protein/creatinine urinary ratio were achieved and remained
      normal up to 1-year post-treatment. 

PMID- 25949469
TI  - Fulminant primary manifestations of Wegener's granulomatosis might not be pauci
      immune.
AB  - Wegener's granulomatosis is an ANCA-associated small vessel vasculitis. Because
      histologically immune complex deposits are frequently lacking, the term pauci
      immune has been introduced for this subgroup. We report a patient with fulminant,
      severe PR3-ANCA-positive Wegener's granulomatosis and multi-organ involvement
      (upper respiratory tract, lung, kidneys, skin and general symptoms), who showed
      pronounced immunoglobulin and complement deposits within the skin biopsy. Our
      observation supports the hypothesis that immune complex deposits may be under
      recognized in early lesions of ANCA-associated Wegener's granulomatosis. 

PMID- 25949470
TI  - An unusual case of (pseudo)hypertriglyceridaemia.
AB  - A high concentration of glycerol in plasma is an interfering factor in the
      determination of triglycerides, giving rise to (pseudo)hypertriglyceridaemia.
      Hyperglycerolaemia may be due to the presence of exogenous glycerol or due to
      endogenous glycerol accumulation. In the present case report, a 57-year-old male
      patient with end-stage renal disease presented with a pseudohypertriglyceridaemia
      based on a pronounced hyperglycerolaemia. The hyperglycerolaemia was due to
      chronic intake of glycerol-containing alcoholic beverages in combination with a
      reduced glycerol clearance and glycerol kinase activity. In conclusion, an
      unexplained hypertriglyceridaemia in patients with an impaired renal function
      should raise the suspicion of hyperglycerolaemia. 

PMID- 25949471
TI  - A not so simple analgesic.
AB  - Many of the common causes of a high anion gap metabolic acidosis, like salicylate
      toxicity or diabetic ketoacidosis, are well recognized and promptly treated.
      Pyroglutamic acidosis (or 5-oxoproline acidosis) is a less common cause and is
      likely substantially underdiagnosed for two reasons: firstly, urine or serum
      measurements of pyroglutamic acid are performed only in specialist laboratories,
      and secondly, because awareness of the condition is still low, despite widespread
      reports in the medical and biochemical literature. The condition is often
      precipitated by the chronic use of paracetamol. Paracetamol is increasingly being
      widely prescribed as an alternative to NSAIDs often in maximal doses, given its
      innocuous reputation, and we anticipate more similar presentations. We present a
      case of a young pregnant woman who developed a severe metabolic acidosis
      secondary to raised pyroglutamate. Her treatment necessitated an emergency
      Caesarean section, ventilation and haemodiafiltration, despite normal renal
      function. We provide a reminder of other risk factors associated with the
      diagnosis. 

PMID- 25949472
TI  - Successful thrombolysis for acute ischaemic stroke in haemodialysis.
AB  - Stroke is a leading cause of death worldwide and is associated with significant
      morbidity in survivors. Early thrombolytic therapy in acute ischaemic stroke has
      been shown to dramatically improve patient outcomes. Although the age-adjusted
      incidence of stroke is 5-10 times greater in haemodialysis patients, the use of
      thrombolysis for this indication in this group of patients has not been described
      to date. We present a case where alteplase was used successfully for acute
      ischaemic stroke in a patient established on maintenance haemodialysis in the
      setting of an international randomized controlled trial and advocate caution with
      the use of systemic thrombolytics despite the favourable outcome seen with this
      case. 

PMID- 25949473
TI  - The kinetics of donor HLA class I-specific antibody absorption following a
      combined split liver and kidney transplant.
AB  - Hyperacute rejection of a transplanted liver is rare even when the recipient has
      circulating donor-specific alloantibodies (DSA). There is also evidence that a
      transplanted liver may provide immunological protection for other organs
      transplanted from the same donor. We monitored the kinetics of circulating DSA in
      a highly sensitized recipient of a combined split liver and kidney transplant and
      demonstrated a reduction in antibody titres immediately after liver perfusion.
      The absorption of DSA was not compromised by the smaller liver mass transplanted.
      DSA titres remained low at 3 months post-transplant, and the recipient did not
      experience antibody-mediated rejection. 

PMID- 25949474
TI  - Lower limb monoparesis due to liquorice consumption.

PMID- 25949475
TI  - A young man presenting with recurrent nephrolithiasis.

PMID- 25949476
TI  - A 76-year-old woman with pre-renal azotaemia and Morgagni's hernia.

PMID- 25949477
TI  - Pneumo-renal sarcoidosis revealed by F-18 FDG PET/CT.

PMID- 25949478
TI  - Pseudoporphyria in a haemodialysis patient.

PMID- 25949479
TI  - A rare cause of massive upper gastrointestinal bleeding in a dialysis patient:
      synchronous Dieulafoy lesions.

PMID- 25949480
TI  - Urinary abnormalities following karate (kumite) competitions.

PMID- 25949481
TI  - Therapy refractory hypertension in haemodialysis patients has become a rare
      indication for bilateral nephrectomy.

PMID- 25949482
TI  - Isolated Aspergillus thyroiditis in an immunocompromised patient.

PMID- 25949483
TI  - A rare presentation of pulmonary hemorrhage with hepatitis C-associated
      cryoglobulinemia and membranoproliferative glomerulonephritis.

PMID- 25949484
TI  - Proteinuria-associated nutcracker syndrome: an amyloid-negative familial
      Mediterranean fever patient.

PMID- 25949485
TI  - Blue toe syndrome as a clue to the underlying cause of acute renal failure.

PMID- 25949487
TI  - Spectrum of sodium hypochlorite toxicity in man-also a concern for nephrologists.
AB  - Sodium hypochlorite (NaOCl) is the active ingredient in household bleach and is a
      very common chemical. It has been used in medical and commercial situations
      dating back to the 18th century for its disinfectant properties, including
      topical use in medicine as an antiseptic. For this indication, NaOCl is a proven
      and safe chemical. However, exposure of NaOCl beyond topical use, whether it is
      intentional or accidental, is associated with significant risks due to its strong
      oxidizing properties. Potentially damaging scenarios include ingestion,
      inhalation, deposition into tissue or injection into the bloodstream. All of
      these scenarios can lead to significant morbidity and even mortality. In this
      review, we examine the toxicity associated with NaOCl exposure and analyze
      potential mechanisms of injury, placing special emphasis on the potential for
      renal toxicity. Due to the extreme ease of access to household bleach products
      and its use in medicine, it is important for the clinician to understand the
      potential damage that can occur in NaOCl exposures so that complications can be
      prevented before they arise. 

PMID- 25949486
TI  - Preserving residual renal function in dialysis patients: an update on evidence to
      assist clinical decision making.
AB  - It has been documented that preservation of residual renal function in dialysis
      patients improves quality of life as well as survival. Clinical trials on
      strategies to preserve residual renal function are clearly lacking. While waiting
      for more results from clinical trials, patients will benefit from clinicians
      being aware of available knowledge. The aim of this review was to offer an update
      on current evidence assisting doctors in clinical practice. 

PMID- 25949488
TI  - Hypernatremia secondary to post-stroke hypodipsia: just add water!
AB  - Disorders in water metabolism may occur in stroke patients. When hypernatremia
      arises in this setting, it is usually secondary to the development of central
      diabetes insipidus or it is the result of neurologic lesions that prevent
      patients from having free access to water. Much rarer are the cases of post
      stroke hypernatremia caused by hypodipsia secondary to lesions of the thirst
      center. We report the case of a patient with severe hypernatremia, probably
      secondary to post-hemorrhagic stroke hypodipsia. The hypernatremia seen in this
      case was corrected by scheduling the patient's water intake. 

PMID- 25949489
TI  - Kikuchi-Fujimoto disease associated with systemic lupus erythematosus.
AB  - A cervical lymph node biopsy from a 38-year-old woman initially revealed
      necrotising lymphadenitis. Her case is presented herein. An exhaustive
      examination that included renal biopsy did not suggest systemic lupus
      erythematosus (SLE). She was diagnosed with Kikuchi-Fujimoto Disease (KFD) and
      was treated with prednisone. One year later, a renal biopsy performed for renal
      failure revealed Class IV SLE. It was proposed that lymphadenitis in this KFD
      patient should be considered as SLE so that the SLE would be properly treated. In
      our patient, this hypothesis was partially correct, because even though SLE could
      not be verified at initial presentation, it evolved into full SLE after a year
      interval. 

PMID- 25949490
TI  - Prolonged renal failure post-percutaneous mechanical thrombectomy.
AB  - Percutaneous mechanical thrombectomy (PMT) has been gaining acceptance as a
      preferred approach for the treatment of acute deep venous thrombosis (DVT). In
      addition to treating acute DVT and decreasing the risk of pulmonary embolism, it
      has been reported that direct extraction of the thrombus decreases the risk of
      post-thrombotic syndrome (PTS), the economic impact of managing which is reported
      to account for 75% of the total cost of management of DVT patients. PMT combines
      localized thrombolysis with mechanical thrombectomy. Recently, there have been
      some reports of reversible acute kidney injury (AKI) occurring post-PMT. The
      pathophysiology of AKI in such cases is due to hemoglobinuria-associated acute
      tubular necrosis. Therefore, the overall prognosis of AKI post-PMT has been
      reported to be good. We report here a case of AKI post-PMT for an extensive DVT
      of the lower extremity whereby the patient continues to require HD even 5 months
      after the procedure. The patient had normal renal function prior to the procedure
      and evidence of hemoglobinuria at the time of diagnosis of AKI. Our case
      illustrates that patients with a large thrombus load may develop severe AKI post
      PMT thus requiring hemodialysis for an extended period of time. Limiting the
      length of time that the mechanical thrombectomy is performed and quantifying the
      amount of effluent obtained would appear to be a prudent practice to reduce the
      risks of renal failure. However, no specific guidelines exist as for the limits
      of hemolysed exudates to be collected. 

PMID- 25949492
TI  - Polycythaemia treated with nephrectomy.
AB  - Unilateral renal cystic disease (URCD) is a rare, non-familial non-progressive
      renal disorder not associated with cysts in other organs in contrast to autosomal
      dominant polycystic kidney disease. Only 55 cases have been published in the
      world literature. Renal diseases are a well-recognized etiology of secondary
      erythrocytosis but not in URCD. We can present at case of URCD and secondary
      polycythaemia. Only one case with similar history has been reported, but in our
      case, the polycythaemia was confirmed by measuring the erythropoietin (EPO) level
      in the cyst fluid. 

PMID- 25949491
TI  - Bilateral renal vein thrombosis due to inapparent polycythaemia.
AB  - Thromboses at unusual sites are characteristic of polycythaemia. We present a
      patient of bilateral renal vein thromboses due to polycythaemia that was
      inapparent. The diagnosis was confirmed by trilineage hyperplasia in bone marrow
      and JAK 2 V617F mutation in blood. 

PMID- 25949493
TI  - Severe hypocalcaemia and hyperphosphataemia caused by oral sodium phosphate fleet
      solution in a haemodialysis patient after parathyroidectomy.
AB  - We report a case with severe electrolyte disturbance after the use of oral sodium
      phosphate solution (OSPS). A 69-year-old patient on haemodialysis received 45 mL
      of OSPS for bowel preparation. He had symptomatic hypocalcaemia with a serum
      calcium level of 0.95 mmol/L and serum phosphate level of 4.73 mmol/L. He was
      treated with haemodialysis and intravenous calcium supplementation. This patient
      had total parathyroidectomy recently leading to the absence of parathyroid
      hormone response. OSPS has been reported to cause life-threatening electrolyte
      disturbance especially in patients with renal failure. We suggest the use of
      safer alternatives for bowel preparations in renal failure patients. 

PMID- 25949494
TI  - Catastrophic hypercalcemia as a technical complication in home hemodialysis.
AB  - Life-threatening hypercalcemia in dialysis patients is very unusual. We present a
      case where life-threatening hypercalcemia in a home hemodialysis patient resulted
      from a technical mistake. A 46-year-old woman, on home nocturnal hemodialysis,
      presented to the emergency room with history of altered sensorium, vomiting and
      sweating, which started 1 h after initiation of dialysis the previous night.
      Serum calcium was 6.5 mmol/L. She improved with 10 h of low-calcium hemodialysis.
      Investigation revealed that the drain port of the reverse osmosis machine was
      connected to the dialysis machine and the product water was connected to the
      drain leading to acute hypercalcemia. 

PMID- 25949495
TI  - Efficacy of crushed lanthanum carbonate for hyperphosphatemia in hemodialysis
      patients undergoing tube feeding.
AB  - Lanthanum carbonate (LaC) is a non-calcium-based phosphate binder used to treat
      hyperphosphatemia in patients with chronic kidney disease. Oral administration of
      LaC is difficult in patients undergoing tube feeding or those who are of advanced
      age because it is essential to chew the LaC tablet sufficiently before swallowing
      it. We report two cases in whom crushed LaC was used in hemodialysis patients
      undergoing tube feeding. In both cases, previously crushed LaC was mixed into
      enteral nutrients. We found that LaC administered this way was effective for
      decreasing serum phosphorus levels. 

PMID- 25949496
TI  - Monoclonal gammopathy of undetermined significance: a contraindication for living
      kidney donation?
AB  - During the last few years, the number of living donor kidney transplants has
      increased and this form of transplantation is currently the only option in some
      patients. We report two cases of living donor kidney transplantation in which the
      donor carried monoclonal gammopathy of undetermined significance. Neither of the
      two receptors has developed complications at 42 and 36 months after
      transplantation, respectively, and the donors have normal renal function and
      there is no evidence of progression to multiple myeloma. 

PMID- 25949497
TI  - Successful kidney transplantation with a well-matched donor despite a positive
      crossmatch; detection and management of sensitization secondary to an alternate
      allelic variant of 'self' HLA.
AB  - Under current UK standards of deceased donor typing, the formation by the
      recipient of HLA antibody against an allelic variant of a 'self' antigen creates
      a particular problem for organ allocation. In the reported case, the decision to
      transplant was taken in the situation of a positive flow crossmatch result
      attributed to allelic antibody. The potential that target antigen density
      contributed to this patient's subsequent good outcome is discussed. 

PMID- 25949498
TI  - tHe USual Suspects.

PMID- 25949499
TI  - An unusual case of hyperphosphatemia in a vitamin D-deficient patient with
      tuberculosis.

PMID- 25949500
TI  - There's something fishy about this bleeding.

PMID- 25949501
TI  - Complete atherosclerotic occlusion of infra-renal aorta and bilateral renal
      artery stenosis.

PMID- 25949502
TI  - Recurrent flank pain from 'lobster claw'.

PMID- 25949503
TI  - A fast-growing skin lesion in a dialysis patient.

PMID- 25949504
TI  - Icodextrin-associated hepatotoxicity.

PMID- 25949505
TI  - Achieving target international normalization ratio in haemodialysis patients with
      atrial fibrillation: is it feasible?

PMID- 25949506
TI  - Intermittent renal graft obstruction by fungal ball-case report.

PMID- 25949507
TI  - Resurgence in home haemodialysis: perspectives from the UK.
AB  - Improvement in dialysis outcomes requires a paradigm shift in haemodialysis
      provision and service design. Haemodialysis at home, recommended by the National
      Institute for Health and Clinical Excellence, can lead to outcome benefits but
      has a range of implementation barriers. This article describes the various
      initiatives in the UK at local, regional and national levels, to provide greater
      patient choice and autonomy, overcome adoption barriers and enable greater uptake
      of this modality. 

PMID- 25949508
TI  - Thinking outside the box-identifying patients for home dialysis.
AB  - Home dialysis modalities are underutilized in the USA with only 8% of the
      dialysis patients undergoing renal replacement therapy at home versus 92% being
      treated with center hemodialysis. This is in contrast to the nephrology
      professionals' opinion about the best dialysis therapy and their potential choice
      in the hypothetical situation of choosing a dialysis modality for themselves. Pre
      dialysis education changes the distribution of dialysis modality significantly,
      as 50% of informed patients choose home dialysis. Close collaboration among
      nephrology professionals, patients and providers is required to make home therapy
      a reality for any interested patient. 

PMID- 25949509
TI  - Integrating peritoneal and home haemodialysis: a nurse's perspective from a
      single centre.
AB  - Home based dialytic therapy is underutilized in most renal centres. This article
      describes a nurse led and delivered approach to problem solving from a patient
      perspective, resulting in an increase in prevalent and incident patient numbers
      on home HD and peritoneal dialysis. Overall, between 2004 and 2010 home-based
      therapies have risen from 61 to 119 prevalent patients, with a fall in in-centre
      patient numbers. 

PMID- 25949510
TI  - Developing an assisted automated peritoneal dialysis (aAPD) service-a single
      centre experience.
AB  - There is an ongoing increase in the number of elderly or frail patients requiring
      renal replacement therapy. Assisted automated peritoneal dialysis (aAPD) is one
      treatment option for this patient group and is becoming increasingly recognized
      as a distinct dialysis modality. In this article, we review the current status of
      aAPD and its evolution across Europe, describing the differences in service
      provision. We also report our experience locally of outcomes on our aAPD
      population over the last 4 years. We found that aAPD is a viable dialysis
      modality in the frail and elderly with limited lifespan, and complications of
      peritoneal dialysis are perhaps lower than would be expected in this population.
      This form of therapy also avoids the disruption to life which results from
      hospital-based dialysis. 

PMID- 25949511
TI  - Anticoagulation and dialysis access practice in home haemodialysis in the UK.
AB  - Anticoagulation is an important component of haemodialysis treatment in all
      settings. The therapeutic options available for anticoagulation of home
      haemodialysis are similar to those for haemodialysis in other settings. However,
      dialysis sessions with a wide range of treatment durations are undertaken at
      home, which can require different approaches to anticoagulation. Conference
      delegates were asked about the types of anticoagulation used in home dialysis and
      about surveillance strategies for monitoring vascular access, and the results are
      presented and discussed. 

PMID- 25949512
TI  - Self-cannulation: enabling patients' independence.
AB  - Home hemodialysis was a modality of necessity in the early days of chronic renal
      replacement therapies. Patients had to be independent for all aspects of their
      care including self-cannulation of the hemodialysis needles. As the number of in
      center staff provided hemodialysis centers has grown, the level of independence
      for hemodialysis patients has drastically decreased. Recent changes by the United
      States Centers for Medicare and Medicaid Services in the 'Conditions of Coverage
      for ESRD' encourages all US dialysis facilities to offer and allow patients to
      perform their own needle cannulation. This article briefly reviews the advantages
      and disadvantages of patient self-cannulation. Self-cannulation can be a stepping
      stone to patient independence including home hemodialysis modality. 

PMID- 25949513
TI  - Home haemodialysis: trends in technology.
AB  - Self management and home-based dialysis therapies offer the prospect of improved
      patient experience and outcomes. To allow more patients to realize these benefits
      requires changes in technology which focus on maximizing the ease and minimizing
      the burdens of undertaking home dialysis. These developments are underway. 

PMID- 25949514
TI  - Personal experiences of home haemodialysis: patients' and carers' experiences.
AB  - The discussions from a patient-led session at a national home haemodialysis
      conference are described. A number of discussion themes are described, together
      with patients' views on technical and social aspects of home dialysis. Issues
      highlighted included the preparation for home systems and the role of intrinsic
      motivation to change regimens and practice. A number of conclusions are drawn
      from the discussion, highlighting the role of patient beliefs about conducting
      haemodialysis at home. 

PMID- 25949515
TI  - Carers perspective on home dialysis: support, facts and legislation.
AB  - Carers provide unpaid care and support to ill, frail or disabled friends or
      family members. It is important for health professionals to give carers of home
      dialysis patients time, space and permission to talk about how caring impacts
      upon their lives and to look at how best to support them. 

PMID- 25949516
TI  - The re-emergence of short daily haemodialysis.
AB  - Thrice weekly in-center hemodialysis is the standard of care for dialysis
      patients with end-stage renal disease (ESRD). However, there is ongoing debate as
      to whether more frequent hemodialysis, with its readier management of both toxin
      and fluid removal, benefits patients. New evidence from recent studies, both in
      center dialysis and in home haemodialysis patients, adds further confirmation of
      improved cardiovascular outcome and quality of life in patients undergoing short
      daily hemodialysis. A paradigm shift in ESRD care delivery may be facilitated due
      to new technology enabling daily therapy at home. 

PMID- 25949517
TI  - Outcomes on home haemodialysis: registry challenges.
AB  - Health care policy is encouraging expansion of home haemodialysis, aiming to
      improve patient outcomes and reduce cost. However, most patient outcome data
      derive from retrospective observational studies, with all their inherent
      weaknesses. Conventional thrice weekly home haemodialysis delivers a 22-51%
      reduction in mortality, but why should that be? Frequent and/or nocturnal
      haemodialysis reduces mortality by 36-66%, with comparable outcomes to deceased
      donor kidney transplantation. Approaches which might improve the quality of
      future observational studies are discussed. Patient-relevant outcomes other than
      mortality are also discussed. 

PMID- 25949518
TI  - Home dialysis-an international perspective.
AB  - Background. There is strong evidence from a range of long-term conditions of
      improved outcomes where patients are involved in self-management. Against this
      background, the international trend for home dialysis continues to decline, with
      centre-based haemodialysis continuing its dominance. Methods. An opinion-based
      commentary exploring practice patterns and drivers for home dialysis
      internationally. Data are drawn from a number of sources including the 2010
      United States Renal Data System report. Results. Drivers behind the use of home
      dialysis are complex including factors relating to the patient and their carers,
      health care team, health care system, geography and cultural factors. There are
      important examples where local champions or public health initiatives have had a
      positive impact on the use of home dialysis; however, in many settings
      significant barriers remain. Better systems for giving patient information,
      shared decision making and involving patients in their own care may have the
      potential to act as a driver for change. Conclusion. Centre-based haemodialysis
      continues to dominate renal replacement therapy internationally with notable
      exceptions. Such dominance suggests that most patients worldwide do not get much
      choice when it comes to modality selection. 

PMID- 25949520
TI  - Home therapies regaining the initiative.

PMID- 25949519
TI  - Enabling self-management: selecting patients for home dialysis?
AB  - Pre-emptive living donor transplantation should always be promoted as the first
      line treatment for kidney failure. Where that is not possible, patients must
      receive timely information and advice regarding all dialysis options available,
      including home-based peritoneal dialysis and haemodialysis. Where a dialysis unit
      enables and actively encourages self-management, patients will tend to select
      themselves, and if well motivated may overcome significant difficulties to exceed
      the expectations or predictions of dialysis staff. Patients then become advocates
      themselves and can provide other patients with the necessary motivation to
      consider a home treatment, such that they approach staff, rather than vice versa.
      For staff to be able to talk to patients with confidence requires direct
      experience of home dialysis, but in units which do not have a full range of home
      therapies, this may initially be difficult. Visiting patients in their home
      environment is an essential part of training for both medical and nursing staff.
      Before a patient is able to begin to engage in discussion about any dialysis
      therapy, they must have reached a point of acceptance that dialysis is necessary.
      If they are not at this point, then any attempt at 'education' will be largely
      futile. Once a patient has arrived at the point of choosing a home therapy, the
      pathway to their first dialysis at home must be as smooth and problem-free as
      possible. 

PMID- 25949521
TI  - Redesigning the regulatory pathway to enhance cellulase production in Penicillium
      oxalicum.
AB  - BACKGROUND: In cellulolytic fungi, induction and repression mechanisms
      synchronously regulate the synthesis of cellulolytic enzymes for accurate
      responses to carbon sources in the environment. Many proteins, particularly
      transcription regulatory factors involved in these processes, were identified and
      genetically engineered in Penicillium oxalicum and other cellulolytic fungi.
      Despite such great efforts, its effect of modifying a single target to improve
      the production of cellulase is highly limited. RESULTS: In this study, we
      developed a systematic strategy for the genetic engineering of P. oxalicum to
      enhance cellulase yields, by enhancing induction (by blocking intracellular
      inducer hydrolysis and increasing the activator level) and relieving the
      repression. We obtained a trigenic recombinant strain named 'RE-10' by deleting
      bgl2 and creA, along with over-expressing the gene clrB. The cellulolytic ability
      of RE-10 was significantly improved; the filter paper activity and extracellular
      protein concentration increased by up to over 20- and 10-fold, respectively,
      higher than those of the wild-type (WT) strain 114-2 both on pure cellulose and
      complex wheat bran media. Most strikingly, the cellulolytic ability of RE-10 was
      comparable with that of the industrial P. oxalicum strain JU-A10-T obtained by
      random mutagenesis. Comparative proteomics analysis provided further insights
      into the differential secretomes between RE-10 and WT strains. In particular, the
      enzymes and accessory proteins involved in lignocellulose degradation were
      elevated specifically and dramatically in the recombinant, thereby confirming the
      importance of them in biomass deconstruction and implying a possible co
      regulatory mechanism. CONCLUSIONS: We established a novel route to substantially
      improve cellulolytic enzyme production up to the industrial level in P. oxalicum
      by combinational manipulation of three key genes to amplify the induction along
      with derepression, representing a milestone in strain engineering of filamentous
      fungi. Given the conservation in the mode of cellulose expression regulation
      among filamentous fungi, this strategy could be compatible with other cellulase
      producing fungi.

PMID- 25949523
TI  - The continuing dilemma of chronic appendicitis.

PMID- 25949522
TI  - Modulation of angiotensin II signaling in the prevention of fibrosis.
AB  - Over the last decade, it has become clear that the role of angiotensin II extends
      far beyond recognized renal and cardiovascular effects. The presence of an
      autologous renin-angiotensin system has been demonstrated in almost all tissues
      of the body. It is now known that angiotensin II acts both independently and in
      synergy with TGF-beta to induce fibrosis via the angiotensin type 1 receptor
      (AT1) in a multitude of tissues outside of the cardiovascular and renal systems,
      including pulmonary fibrosis, intra-abdominal fibrosis, and systemic sclerosis.
      Interestingly, recent studies have described a paradoxically regenerative effect
      of the angiotensin system via stimulation of the angiotensin type 2 receptor
      (AT2). Activation of AT2 has been shown to ameliorate fibrosis in animal models
      of skeletal muscle, gastrointestinal, and neurologic diseases. Clinical reports
      suggest a beneficial role for modulation of angiotensin II signaling in cutaneous
      scarring. This article reviews current knowledge on the role that angiotensin II
      plays in tissue fibrosis, as well as current and potential therapies targeting
      this system. 

PMID- 25949524
TI  - Early 'shallow' needle-knife papillotomy and guidewire cannulation: an effective
      and safe approach to difficult papilla.
AB  - INTRODUCTION: Needle-knife sphincterotomy (NKS), known as 'precut', is used
      worldwide to facilitate access to the common bile duct when standard cannulation
      has failed. This procedure is considered hazardous because it is burdened with
      high procedural related complications (bleeding and perforation). Its right
      timing is still debated. In this study we report our results using a modified
      precut approach, early shallow needle-knife papillotomy (eSNKP) coupled with
      guidewire cannulation in case of difficult papilla. We evaluated its safety and
      effectiveness. METHODS: From 2012 to 2014, 1034 patients underwent therapeutic
      ERCP. A total of 138 of them presented difficult papilla and were treated with
      eSNKP performed after 5 failed attempts of standard guidewire cannulation. Deep
      biliary cannulation rate was recorded, as well as intraoperative and
      postoperative complication rate. RESULTS: Successful biliary deep cannulation was
      achieved in 132/138 patients (95.7%) by means of eSNKP. In 6 patients (4.3%),
      cannulation failed even after eSNKP. ERCP was newly performed 72 hours later with
      successful and immediate guidewire biliary cannulation. Overall morbidity was
      10.1% (14/138). No perforation occurred. Minor bleeding occurred in 4/138 cases
      (2.9%) and 10/138 patients (7.2%) developed mild pancreatitis. CONCLUSION: In
      case of difficult papilla, eSNKP followed by guidewire cannulation increases the
      successful deep biliary cannulation with low rate of complications.

PMID- 25949525
TI  - Cannulation of the biliary tree under endoscopic control with an echoendoscope,
      without fluoroscopy: report of a case series.
AB  - INTRODUCTION: Endoscopic ultrasonography (EUS) is a validated technique allowing
      precise diagnosis and staging of pancreatic, biliary and ampullary disease.
      Developments in instruments and accessories have led to a more extensive use of
      this technology to perform operations. The use of EUS as an operative technique,
      alone or in conjunction with other endoscopic procedures, has already been
      described in the literature in several reports. However, despite the use of EUS,
      fluoroscopy has always been required to perform these operations. There are no
      data in the literature describing the feasibility, safety and efficacy of
      operative EUS in the treatment of common bile duct (CBD) obstruction, following a
      malignant or benign disease, performed completely under EUS guidance without
      fluoroscopic assistance. METHODS: In this series we describe three cases of EUS
      treatment of CBD diseases performed without fluoroscopic assistance. RESULTS: All
      the cases were treated by EUS without fluoroscopic assistance and no
      complications were encountered. CONCLUSION: Operative EUS without fluoroscopy
      appears to be a feasible technique. Its major advantages could be to shorten the
      examination time and to enable biliary or pancreatic operative endoscopy in
      patients in whom fluoroscopy could be dangerous, such as pregnant women. The
      endoscopist should have a good training both in EUS and endoscopic retrograde
      cholangiopancreatography. Prospective, larger studies are needed to confirm our
      preliminary data.

PMID- 25949526
TI  - The clinical potential of ramosetron in the treatment of irritable bowel syndrome
      with diarrhea (IBS-D).
AB  - Irritable bowel syndrome (IBS) is a highly prevalent functional bowel disorder.
      Serotonin (5-HT) is known to play a physiological and pathophysiological role in
      the regulation of gastrointestinal function. In experimental studies, 5-HT3
      receptor antagonists have been reported to slow colon transit, to blunt
      gastrocolonic reflex, and to reduce rectal sensitivity. Alosetron and
      cilansetron, potent and selective 5-HT3 receptor antagonists, have proven
      efficacy in the treatment of IBS with diarrhea (IBS-D). However, alosetron was
      voluntarily withdrawn due to postmarketing reports of ischemic colitis and
      complications of constipation, and cilansetron was never marketed. Currently
      alosetron is available under a risk management program for women with severe IBS
      D. Ramosetron is another potent and selective 5-HT3 receptor antagonist, which
      has been marketed in Japan, South Korea, and Taiwan. In animal studies,
      ramosetron reduced defecation induced by corticotrophin-releasing hormone and had
      inhibitory effects on colonic nociception. In two randomized controlled studies
      including 957 patients with IBS-D, ramosetron increased monthly responder rates
      of patient-reported global assessment of IBS symptom relief compared with
      placebo. Ramosetron was also as effective as mebeverine in male patients with IBS
      D. In a recent randomized controlled trial with 343 male patients with IBS-D,
      ramosetron has proved effective in improving stool consistency, relieving
      abdominal pain/discomfort, and improving health-related quality of life.
      Regarding safety, ramosetron is associated with a lower incidence of constipation
      compared with other 5-HT3 receptor antagonists and has not been associated with
      ischemic colitis. Although further large prospective studies are needed to assess
      whether ramosetron is effective for female patients with IBS-D and to evaluate
      its long-term safety, ramosetron appears to be one of the most promising agents
      for patients with IBS-D. 

PMID- 25949528
TI  - Chronic appendicitis: uncommon cause of chronic abdominal pain.

PMID- 25949527
TI  - From historical perspectives to modern therapy: a review of current and future
      biological treatments for Crohn's disease.
AB  - Crohn's disease (CD) is a debilitating, systemic inflammatory disorder with both
      gastrointestinal and extraintestinal manifestations. Its existence predates
      modern medicine, but its precise etiology remains incompletely understood. Most
      authorities suggest a multifactorial pathogenesis owing to a mixture of genetic
      disorders, immunologic dysregulation, microbiota disequilibrium and environmental
      influences. Of these factors, the overactive immunologic response seen in CD
      appears to be the most promising target of medical therapy. Biological agents
      comprise a relatively new class of drugs that can induce and maintain remission
      in moderate to severe CD, as well as in ulcerative colitis. This review will
      provide an overview of CD, its history, clinical features, pathophysiology, and
      treatment options focusing on current and future biological agents with an
      emphasis on drug development, dosage and administration. 

PMID- 25949530
TI  - Erratum to: a SNP profiling panel for sample tracking in whole-exome sequencing
      studies.
AB  - This is an Erratum to Genome Medicine 2013, 5:89, highlighting an error in Table
      1 of the original article. Please see related article:
      http://genomemedicine.com/content/5/9/89.[This corrects the article DOI:
      10.1186/gm492.]. 

PMID- 25949531
TI  - Welcome to the london journal of primary care.

PMID- 25949532
TI  - Epidemiology and public health in primary care: looking back and forward - 30
      years after Alma Ata.

PMID- 25949533
TI  - Non-medical perspectives within primary care.

PMID- 25949529
TI  - Human phenotype ontology annotation and cluster analysis to unravel genetic
      defects in 707 cases with unexplained bleeding and platelet disorders.
AB  - BACKGROUND: Heritable bleeding and platelet disorders (BPD) are heterogeneous and
      frequently have an unknown genetic basis. The BRIDGE-BPD study aims to discover
      new causal genes for BPD by high throughput sequencing using cluster analyses
      based on improved and standardised deep, multi-system phenotyping of cases.
      METHODS: We report a new approach in which the clinical and laboratory
      characteristics of BPD cases are annotated with adapted Human Phenotype Ontology
      (HPO) terms. Cluster analyses are then used to characterise groups of cases with
      similar HPO terms and variants in the same genes. RESULTS: We show that 60% of
      index cases with heritable BPD enrolled at 10 European or US centres were
      annotated with HPO terms indicating abnormalities in organ systems other than
      blood or blood-forming tissues, particularly the nervous system. Cases within
      pedigrees clustered closely together on the bases of their HPO-coded phenotypes,
      as did cases sharing several clinically suspected syndromic disorders. Cases
      subsequently found to harbour variants in ACTN1 also clustered closely, even
      though diagnosis of this recently described disorder was not possible using only
      the clinical and laboratory data available to the enrolling clinician.
      CONCLUSIONS: These findings validate our novel HPO-based phenotype clustering
      methodology for known BPD, thus providing a new discovery tool for BPD of unknown
      genetic basis. This approach will also be relevant for other rare diseases with
      significant genetic heterogeneity.

PMID- 25949535
TI  - A London view.

PMID- 25949536
TI  - The international section.

PMID- 25949534
TI  - Welcome to the ethics section of the London Journal of Primary Care.

PMID- 25949537
TI  - Type 2 diabetes: follow up.
AB  - CASE HISTORY: A 41 year old accountant recently registered with your practice.
      His registration health check indicates: BMI 31, BP 150/95, urine 1 + of glucose,
      no protein, smoker of 15 cigarettes daily. He has had diabetes for seven years
      and is taking Metformin 500 mg four times daily. It has been over a year since he
      last saw a doctor and he has now come to see you to obtain a prescription for
      medication.

PMID- 25949538
TI  - A practical guide to the diagnosis and management of insomnia in a general
      practice consultation.
AB  - CASE HISTORY: A 43 year old woman presents with difficulty sleeping for five
      weeks and still feeling very tired when she wakes up. This has been adversely
      affecting her work performance. Additionally, she has recently had relationship
      problems with her husband. She burst into tears at work three days ago, which she
      has never done before and this has finally prompted her to come and see you.

PMID- 25949540
TI  - The Professor Lord Darzi interview.

PMID- 25949539
TI  - The Darzi interview: an opportunity for debate.

PMID- 25949541
TI  - Lay perspective: is it enough that they belong ....

PMID- 25949542
TI  - GP perspective.

PMID- 25949543
TI  - A nursing perspective.

PMID- 25949544
TI  - Pharmacy perspective.

PMID- 25949546
TI  - Russian perspective: a note from the motherland of polyclinics.

PMID- 25949545
TI  - PCT perspective: primary care is more than health.

PMID- 25949547
TI  - An historical perspective.

PMID- 25949548
TI  - Interprofessional learning perspective.

PMID- 25949549
TI  - Workforce development perspective.

PMID- 25949550
TI  - USA perspective: polyclinics must integrate health care vertically AND
      horizontally.

PMID- 25949552
TI  - An organisational behaviour perspective: current issues in the organisation,
      management and politics of primary care.

PMID- 25949551
TI  - A policy perspective.

PMID- 25949553
TI  - Welcome to london landscape!

PMID- 25949554
TI  - An account of my life.
AB  - This is the first instalment of the autobiography of John Horder. He intended it
      to be read solely by family and friends. However the London Journal of Primary
      Care subsequently persuaded him to let us serialise it for a wider readership.
      Those of you who are registered with the journal will be informed when new
      chapters are posted on the website. The autobiography as a whole is an important
      piece of history. It is remarkable for its humanity, perception and humility -
      much like the man himself. John is a founding father of modern general practice.
      He was doing his medical finals when the NHS was founded in 1948 and has been an
      active advocate of whole person, family and community-oriented general practice
      ever since. He became active in the College of General Practitioners shortly
      after its formation in 1952 and before it gained its Royal Charter in 1967. He
      was one of the two founders of the Leeuwenhorst European Study Group that defined
      the job description of a general practitioner in 1974. He was President of the
      RCGP between 1979 and 1982. He assisted the setting up of general practice
      educational bodies in several Western European countries, especially Yugoslavia
      and Portugal. He has been a tireless supporter of interdisciplinary learning and
      founded the Centre for the Advancement of Inter-professional Education (CAIPE) in
      1987. He lives in Primrose Hill with his wife Elizabeth June, who was also his
      partner in general practice. Abridged by Maria Guihen (Ealing PCT). 

PMID- 25949555
TI  - The diving bell and the butterfly (le scaphandre et le papillon).

PMID- 25949556
TI  - The terracotta army.

PMID- 25949557
TI  - Diabetes intermediate care services in Hounslow.
AB  - Practice based commissioning (PBC), payment by results and financial deficits
      have all placed a financial imperative on primary care trusts (PCT) to deliver
      savings by reducing referrals to secondary care. In many London PCTs, referrals
      to secondary care diabetes services have been a priority and this has led to
      intermediate PCT led services springing up all over London. Hounslow Diabetes
      Intermediate Care Service is one of them and at a time when many PBC groups are
      trying to develop intermediate services I sent Lauren Baines to meet the Hounslow
      team and tell us about their journey to becoming a well established service. 

PMID- 25949558
TI  - Primary Health Care in London: onwards from Alma Ata.

PMID- 25949559
TI  - Healthcare organisation and systems: that's interesting!

PMID- 25949560
TI  - Mental health services in metropolitan primary care. The unique challenges and
      opportunities.

PMID- 25949561
TI  - The EVIDEM programme: a test for primary care research in London?
AB  - KEY MESSAGES: The emphasis in NHS Research and Development is shifting towards
      the 'D' component, and primary care is better placed than traditional academia to
      use the opportunities that this shift will create.Multidisciplinary working and
      collaboration between institutions that are competitive are possible, and may
      even be easier to achieve through primary care because of its collaborative
      traditions.The fragmentary nature of London's health and social services, and the
      diversity of the population, are a challenge to all research and development
      work.The bureaucracy of research governance, and the risk aversion that it
      contains, are a problem for research and development. WHY THIS MATTERS TO ME:
      This paper matters to me for two reasons, one to do with applied research and the
      other to do with ageing and neurodegenerative diseases.

PMID- 25949562
TI  - The Practitioner Health Programme: a free and confidential health service for
      doctors and dentists in London.
AB  - This article describes a free and confidential service available to doctors and
      dentists living or working in the London area and who are suffering from mental
      health, addiction or physical health concerns that may be affecting their work.
      The service is led by an experienced general practitioner and includes free and
      timely access to specialist services. The service will begin to accept referrals
      from October 2008. Please consult the web site for details: www.php.nhs.uk. 

PMID- 25949563
TI  - Silently lost in a sea of infections.
AB  - KEY MESSAGES: This article highlights some of the problems faced in working in
      resource poor settings. While the situation may differ from general practice in
      London, many of the same principles apply.It highlights the importance of keeping
      hearing loss in mind when seeing children with other conditions.It shows some of
      the principles in the Alma Ata declaration, such as the inequity in treatment
      between developed and developing world settings, health care rationing and the
      concept of health including social well-being. WHY THIS MATTERS TO ME: This
      article relates to my time working in Pakistani Kashmir for a medical NGO in both
      primary and secondary care paediatrics. It describes trying to help a young girl
      with hearing loss. Particularly in a setting like this, you tend to prioritise
      the immediate problems (mostly infections in infants) and ignore other things
      however difficult they may be for the child and family. Most importantly I feel
      this article provides a different perspective, giving a first hand account of
      dealing with a difficult problem in a difficult setting. While not directly
      related to general practice in London, this article provides many important and
      relevant messages. Neonatal hearing screening may mean that congenital hearing
      loss is picked up at birth, but other forms will present at a later stage and
      children who have not been screened (who missed the screening, parental refusal
      and those who came from overseas) still need to be considered. Thirty years on
      from the Alma Ata conference the world is still blighted by many of the same
      problems. This personal account shows many of the difficulties spelt out by the
      declaration. In particular it highlights the persisting inequity in treatment
      between the developed and developing world. It shows the importance of health
      including social well-being. The girl in this story lacked a disease, but being
      unable to hear, or more importantly communicate, would mean an inability to live
      an independent life in the future. Another concept highlighted is health
      rationing, which is faced almost daily in any field of medicine. This is
      especially so in fragile states and war zones. External health funding goes
      predominantly to 'fashionable' diseases such as HIV, which has lead to
      organisations trying to promote the 'neglected' diseases, for example
      trypanosomiasis. Despite its debilitating effects hearing loss achieves even less
      attention than these.

PMID- 25949564
TI  - The enduring legacy of Alma Ata: 30 years on.
AB  - The 1978 Alma Ata conference and declaration was a landmark in defining and
      providing a direction for primary healthcare. Despite the initial enthusiasm for
      Alma Ata, its impact appeared to have declined in the 1990s. However, in recent
      years, there has been a revitalisation of primary healthcare. This article
      reviews the Alma Ata conference and declaration, assesses its waxing and waning,
      and examines its recent revival. The paper draws conclusions about the relevance
      of Alma Ata, 30 years on. 

PMID- 25949565
TI  - Primary Health Care: an obituary?

PMID- 25949566
TI  - Comprehensive Primary Health Care: a new phase?

PMID- 25949567
TI  - Potential of the next stage review.

PMID- 25949568
TI  - Making a reality of the slogan.

PMID- 25949570
TI  - Myths and realities in multidisciplinary team-working.

PMID- 25949569
TI  - Is the traditional family doctor an anachronism?
AB  - KEY MESSAGES: The polyclinics debate should recognise the need to balance the
      benefits of long-term personal doctor-patient relationship with the broader
      improved health outcomes from evidence based inputs from multidisciplinary teams
      in primary care. There is increasing evidence from the international health
      literature that a focus on integrated health systems is the key to better health
      outcomes both at the individual and population levels, in addition to being more
      cost effective. Although there is some evidence that other healthcare
      professionals such as nurse practitioners can deliver equally high health
      outcomes for patients, the GP role is not an anachronism and even seems
      increasingly more important in the 21st century given the increasing complexity
      of primary care and long term conditions.

PMID- 25949571
TI  - Participation, equity and inter-sectoral collaboration in general practice: the
      case of Vauxhall Primary Health Care.

PMID- 25949572
TI  - Healthier happier children.

PMID- 25949573
TI  - Complementary therapies in the NHS: some thoughts and three cases.

PMID- 25949574
TI  - The spirit of Alma Ata in Europe today.

PMID- 25949575
TI  - 'The best is the enemy of the good': delivering health care in sub-Saharan
      Africa.

PMID- 25949576
TI  - Reflections on Alma Ata, and 60 years of the NHS.

PMID- 25949577
TI  - An account of my life.
AB  - This is the second instalment of the autobiography of John Horder. It was
      originally written for his grandchildren to read. The autobiography as a whole is
      an important piece of history. It is remarkable for its humanity, perception and
      humility - much like the man himself. John is a founding father of modern general
      practice. He was doing his medical finals when the NHS was founded in 1948 and
      has been an active advocate of whole person, family and community-oriented
      general practice ever since. He was one of the two founders of the Leeuwenhorst
      European Study Group that defined the job description of a general practitioner
      in 1974. He was President of the Royal College of General Practitioners between
      1979 and 1982. He assisted the setting up of general practice educational bodies
      in several Western European countries, especially Yugoslavia and Portugal. He has
      been a tireless supporter of inter-disciplinary learning and founded the Centre
      for the Advancement of Inter-professional Education (CAIPE) in 1987. He lives in
      Primrose Hill with his wife Elizabeth June, who was also his partner in general
      practice. Abridged by Maria Guihen (Ealing PCT). 

PMID- 25949579
TI  - Bach and clinical care: a proposition.

PMID- 25949578
TI  - Divisionists: an exhibition at the National Gallery, London.

PMID- 25949580
TI  - How to stay in love with general practice.

PMID- 25949581
TI  - EACH (European Association for Communication in Healthcare) International
      Conference 2008, 2-5 September 2008, Oslo, Norway.

PMID- 25949582
TI  - Improving end of life care: a matter of life and death.
AB  - KEY MESSAGES: End of Life Care is important - it affects us allMost people die of
      co-morbidity/non-cancer conditions in old ageToo few people die in their place of
      choice, usually at homeHospital deaths are expensive and often preventableMost
      end of life care is from the usual generalist providerThere is much that can be
      done; we are all involved and can play an important part in the delivery of top
      quality care.

PMID- 25949584
TI  - Support the journal.

PMID- 25949583
TI  - Does suicide always indicate a mental illness?

PMID- 25949585
TI  - Promoting high quality care for all at the end of life: review of NHS National
      End of Life Care Programme 2004-2007 and implications for primary care.
AB  - Background Research shows most people want to die at home yet most in fact die in
      hospital. The underlying reason for this mismatch is that health and social care
      services struggle to respond satisfactorily to people's varying end of life care
      needs. The creation of the National End of Life Care Programme in 2004(1) and the
      launch of the End of Life Care Strategy in 2008(2) were designed to improve this
      situation. Setting The National End of Life Care Programme was set up to offer
      patients nearing the end of their life high quality care and choices about where
      to die. Particular objectives were reducing the number of unnecessary emergency
      admissions and improving the skills of the workforce. Question How effective has
      the National End of Life Care Programme been in its first three years? And given
      that an increasing proportion of end of life care services will take place in the
      community, what are the implications for primary care staff? Methods The authors
      discuss an in-depth evaluation of the National End of Life Care Programme by
      Nottingham University.(3) They also describe two Department of Health reports
      indicating how primary care services can improve the quality of end of life care
      services.(4,5) Results The Nottingham University evaluation shows that the
      National End of Life Care Programme is having an impact. SHAs with high uptake of
      end of life care tools tend to have higher rates of home deaths. In addition
      staff who use the tools are more confident in broaching sensitive issues around
      dying. Meanwhile the DH reports provide a template for coordination of services
      and training of staff in the community. Conclusion There are examples around the
      country of excellent end of life care. But it is essential that the best is
      spread to the rest. That success depends on better organisation and
      collaboration, effective use of resources and good communication between
      commissioners and providers. Above all, care has to be focused on the individuals
      and their carers. 

PMID- 25949586
TI  - Centralisation of end of life care coordination: impact on the role of community
      providers.
AB  - Background The recently published End of Life Care Strategy (1) and emerging
      service improvements have raised the profile of end of life care (EOLC) across
      health and social care sectors. Policy emphasises providing patients with more
      choice over where they are cared for at the end of life. Surveys and anecdotal
      evidence suggest that the majority of people would prefer to be cared for (and
      die) in their own home. Such care provision evidently requires considered
      planning across community providers. Some areas have instigated a centralised
      administrative process for such care planning. Setting This shift towards
      centralising the administrative function of care coordination for patients who
      are nearing the end of life has implications for community care providers.
      Question This paper seeks to understand the impact that centralising EOLC care
      coordination in the community has had on community providers. Methods This paper
      draws on findings from case studies of two large primary care trust (PCT) regions
      in England. One hundred and two semi-structured interviews with service managers,
      commissioners and providers were conducted across the two case studies, as well
      as two focus groups (ten participants - acute and community nurses), observation
      of key local palliative care planning meetings, and documentary analysis of
      strategic and operational papers. Results The findings presented demonstrate that
      a centralised approach to care planning has positive outcomes for community
      nurses, who are able to spend more time delivering direct patient care. However,
      there were challenges associated with the approach - particularly the capacity of
      an administrative process to intelligently allocate finite resources amongst
      patients with a range of care needs. Conclusions The centralisation of care
      planning had implications for how community nurses conceptualised their role in
      the delivery and coordination of EOLC. Community nurses were positive regarding
      the alleviation of the administrative burden; however the approach challenged
      their professional role as key worker - particularly in making judgements as to
      the nature and appropriateness of patient care packages. 

PMID- 25949588
TI  - Networking to improve end of life care.
AB  - Network organisations are increasingly common in healthcare. This paper describes
      an example of clinically led networking, which improved end of life care (EOLC)
      in care homes, differentiating between a 'network' as a formal entity and the
      more informal process of 'networking'. The paper begins with a brief discussion
      of networks and their development in healthcare, then an overview of EOLC policy,
      the case setting and methods. The paper describes four key features of this
      networking; (1) how it enabled discussions and implemented processes to help
      people address difficult taboos about dying; (2) how personal communication and
      'distributed leadership' facilitated learning; (3) how EOLC occasionally lapsed
      during the handover of patient care, where personal relationship and
      communication were weaker; and (4) how successful learning and sharing of best
      practice was fragile and could be potentially undermined by wider financial
      pressures in the NHS. 

PMID- 25949587
TI  - Primary and secondary care collaboration for end of life care.
AB  - Background The NHS does not deliver the care that people want at the end of life
      and receives large numbers of complaints about care in hospitals. This is a
      symptom of a wider problem which leads to over-hospitalisation of elderly people.
      This was demonstrated clearly in a hospital utilisation study in a south London
      borough which showed that over 40% of patients needed to be cared for in settings
      other than the hospital. Community services were also providing care
      inappropriately. Discussion Three issues need to be addressed: 1. An integrated
      community service, working with both general practice and consultants from the
      hospital to provide a flexible response to patients' needs over time. This would
      focus on maintaining people in the community rather than admitting them to
      hospital. This would be true for people approaching the end of their lives. 2.
      Additional, flexible service capacity both in people's homes and in bed-based
      services including for those people awaiting a continuing care assessment. 3. A
      system of incentives for hospitals to shift their approach to managing such
      patients. With these things in place, the delivery of the end of life care
      service that people have expressly said they want will be feasible. 

PMID- 25949589
TI  - Inter-organisation communication for end of life care.
AB  - Background Poor communication between in-hours and out-of-hours (OoH) general
      practitioners (GPs) causes unwanted admissions to hospital of patients who want
      to die at home Setting A GP OoH service in West London (London Central and West
      Unscheduled Care Service) used by 159 general practices from four primary care
      trusts Question What helps to avoid hospital admission of patients who want to
      die at home when a crisis occurs in the OoH period? Methods Whole system
      participatory action research, with four stages: 1. engage stakeholders; 2.
      understand the initial situation; 3. re-design the system; 4. action for change
      Results The following help to avoid undesirable hospital admission of a dying
      person who has a crisis in the OoH period: 1. a register of vulnerable adults; 2.
      records at home; 3. key worker(s); 4. home interventions; 5. day-time
      practitioner communication; 6. a development and governance group; 7. speedy
      discharge from hospital; 8. decision support for OoH GPs. Discussion This project
      revealed a useful set of policies to help avoid unnecessary OoH admission to
      hospital, especially improved communication between day-time GPs and OoH GPs. The
      approach combined whole system participatory action research with systems
      modelling and this helped the issues to be revealed quickly and cheaply.
      Furthermore, including leaders from partner organisations at each stage of the
      inquiry has encouraged shared purpose and produced champions to move forward the
      project recommendations. Some changes have already happened. 

PMID- 25949590
TI  - Permanent vegetative state: comparing the law and ethics of two tragic cases from
      Italy and England.

PMID- 25949591
TI  - Death certification: topical tips for GPs.

PMID- 25949592
TI  - Service development or research: make sure you know which game you are playing.
AB  - Background Benign headache is a common neurological symptom in both primary care
      (5% of consultations) and secondary care (20-30% of neurology referrals).
      Question Does a simple patient information sheet improve headache severity,
      frequency and impact as measured by the HIT-6 score? Methods A randomised
      controlled trial (RCT) in an NHS setting. Results The trial terminated early due
      to incomplete recruitment over a two year period. The information sheet had
      strong face validity with patients and patient groups but no meaningful
      conclusions can be drawn because of recruitment problems. One hundred and sixty
      eight patients were randomised from a projected sample size of 220 and only 62
      fully completed the trial. Conclusions We analysed the reasons for trial failure,
      and they fall into a number of distinct groups: (1) major service
      configuration/re-orientation occurred concurrently as the trial was run with
      'Choose and Book' and the '18 week targets' being introduced; (2) our aim was a
      classical evidence-based superiority trial, whereas the PCT aim was demand
      management; (3) there was a funding and resource shortfall. Our experience
      generates discussion about appropriate level of evaluation required for service
      development. 

PMID- 25949593
TI  - Croup calculator: frequently asked questions.

PMID- 25949594
TI  - General practice, clinical intention and the Sexual Offences Act 2003.
AB  - General practitioners must be capable of regularly taking 'ultimate'
      responsibility for difficult decisions in situations of clinical complexity and
      uncertainty. The Sexual Offences Act 2003 criminalises all sexual activity with a
      child under the age of 16. However, those who act with the purpose of protecting
      a child from a sexually transmitted infection, protecting the physical safety of
      a child, preventing the child from becoming pregnant or promoting the child's
      emotional well-being by the giving of advice will not commit an offence.
      Medicolegal academic writers have compared the legal separation of intention and
      foreseeability with the special defence of double-effect used in the palliative
      care context. This paper seeks to draw upon legal principles in constructing an
      ethical framework for analysis of this issue. It is hoped that this case study
      will stimulate further discussion, clarify the moral reasoning underpinning the
      existing guidelines for GPs and how the doctrine or principle of double effect
      can be used outside the palliative medicine context. 

PMID- 25949595
TI  - End hand-written referral! Create referral forms in EMIS LV.

PMID- 25949596
TI  - Have new NHS market reforms learned from failings of old?

PMID- 25949597
TI  - Falls prevention in primary care.
AB  - Each year 1.57 million older people fall more than three times and 70 000
      fracture their hips. Falls can lead to disability and even death. The NSF for
      Older People identified falls prevention as a major health priority. This paper
      explains how primary care practitioners can contribute to falls prevention,
      reduce falls risk and improve quality of life for the older person. 

PMID- 25949598
TI  - GP trainees and revalidation.
AB  - GP trainees surveyed GP trainees in the London Deanery to ask their views about
      revalidation, and have found there are significant perceived deficiencies in
      knowledge, engagement, and faith in plans. 

PMID- 25949599
TI  - The job situation.

PMID- 25949600
TI  - WONCA Europe 2009: reflections and personal highlights.
AB  - WHY THIS MATTERS TO US: In April 2009 we launched the RCGP Junior International
      Committee, the UK representative body to the Vasco da Gama Movement. Since then
      we have worked hard to establish a network of UK trainees and junior GPs with an
      interest in international primary care, as well as promote international exchange
      and research. This year's WONCA Europe conference was a great success for the
      group with the presence of a strong UK contingent. We hope to repeat this success
      next year and inspire an even greater number of trainees and junior GPs to take
      part in international conferences and clinical exchange.

PMID- 25949602
TI  - That was then, this is now....

PMID- 25949601
TI  - An account of my life.
AB  - This is the fourth instalment of the autobiography of John Horder. He intended it
      to be read solely by family and friends. However LJPC persuaded him to serialise
      it for a wider readership. The autobiography as a whole is an important piece of
      history. It is remarkable for its humanity, perception and humility - much like
      the man himself. John is a founding father of modern general practice. He was
      doing his medical finals when the NHS was founded in 1948 and has been an active
      advocate of whole person, family and communityoriented general practice ever
      since. He became active in the College of General Practitioners shortly after its
      formation in 1952 and before it gained its Royal Charter in 1967. He was one of
      the two founders of the Leeuwenhorst European Study Group that defined the job
      description of a general practitioner in 1974. He was President of the RCGP
      between 1979 and 1982. He assisted the setting up of general practice educational
      bodies in several Western European countries, especially Yugoslavia and Portugal.
      He has been a tireless supporter of inter-disciplinary learning and founded the
      Centre for the Advancement of Inter-professional Education (CAIPE) in 1987. He
      lives in Primrose Hill with his wife Elizabeth June, who was also his partner in
      general practice. Abridged by Layla Stock (Ealing PCT). 

PMID- 25949603
TI  - International forum on quality and safety in health and care: 17-20 march 2009,
      berlin.

PMID- 25949604
TI  - Like mother, like son.

PMID- 25949605
TI  - Henry VIII: man and monarch.

PMID- 25949606
TI  - Sheila.

PMID- 25949607
TI  - London's children: more than mini adults.

PMID- 25949608
TI  - Health, inequality and child poverty in London.

PMID- 25949609
TI  - Safeguarding: the missing seat at the table.

PMID- 25949610
TI  - Child health: general practitioners (GPs) and the care of children and young
      people.

PMID- 25949611
TI  - Primary care management of acute illness in children.

PMID- 25949612
TI  - Choosing for and with children: consent, assent and working with children in the
      primary care setting.
AB  - The complex ethical and legal concepts of consent, assent, capacity and best
      interests merit a fine-grained scrutiny in the context of providing health care
      for children. Empirical evidence points to children being much more competent
      than we are often prepared to admit and their views and concerns not always being
      given sufficient attention. Various models and guidelines help practitioners to
      redress this deficit and to assist in shared decision making between children and
      their parents. In addition, there is a case for adopting a more family centred
      perspective rather than an adversarial legalistic approach. 

PMID- 25949613
TI  - Managing the unwell child.
AB  - Managing the unwell child can be a frightening experience for everyone involved.
      As GPs become more involved in delivery of care in Urgent Care Centres and
      Emergency Units, it is more likely that they will come across a child who is
      sicker than those attending the surgery. This article will help the GP and the
      rest of the team to be prepared for this situation - to identify the unwell
      infant or toddler, to know general management principles and some specific
      treatment pathways for common emergencies and to take steps to try and prevent
      children becoming critically ill wherever possible. Local management pathways may
      vary so please refer to your local guidelines. Advice from national bodies such
      as the UK Resuscitation Council, the Advanced Life Support Group and the British
      National Formulary for Children has been included. Please revisit these resources
      for updated material. 

PMID- 25949614
TI  - Common eye problems among children.
AB  - The following article discusses four common paediatric ophthalmology
      presentations to primary care. A simple approach to assessment of children with
      these presentations is described. 

PMID- 25949615
TI  - Managing vitamin D deficiency in children.
AB  - Vitamin D deficiency has been identified in many British children. This condition
      has many deleterious effects on their health. Taking vitamin D status into
      account needs to become a daily element of primary care practice, both in
      antenatal and postnatal situations. It is probable that a significant improvement
      in reducing chronic diseases in adulthood will result from a more proactive
      approach in children. 

PMID- 25949616
TI  - Antibiotic prescribing for upper respiratory tract infections in children: how
      can we improve?
AB  - Upper respiratory tract infection (URTI) in children is one of the most common
      problems that general practitioners (GPs) see. Although complications from URTIs
      are rare, and antibiotics offer little or no benefit in uncomplicated cases,
      antibiotic prescribing has increased in recent years following a decline in the
      late 1990s. This article explores possible reasons for the increase, weighs the
      evidence on withholding antibiotics and asks how GPs will interpret recent
      National Institute for Health and Clinical Excellent (NICE) guidelines when
      dealing with URTI in children. We review some of the latest approaches to help
      implement antibiotic prescribing guidelines and suggest some practical solutions
      to help busy GPs. 

PMID- 25949617
TI  - Addressing an overweight child and an unaware parent in the general practice
      consultation.
AB  - KEY MESSAGES: General practitioners (GPs) can play a key role in tackling the
      current obesity epidemic, especially helping parents who may not realise that
      their child is overweight. In a ten-minute consultation, a GP should: explore a
      parent's ideas, concerns and expectations about food and exercise and build a
      picture of the home environmentexclude medical causes of overweight and plot
      height and weight on a growth chartoffer practical strategies and achievable
      goals, agree follow up and involve the multidisciplinary team for support. WHY
      THIS MATTERS TO ME: Childhood obesity is a global epidemic that has significant
      impact on the physical and psychological health and development of children, and
      often persists into adulthood where the health sequelae are well known. Parents
      are key players in putting healthy living advice into practice but our recent
      systematic review showed that parents are poor at recognising overweight in their
      own children. We believe GPs are key to providing health promotion for this
      group. However, to approach this sensitive subject requires one to have
      confidence and skills at one's fingertips and we hope this guide can provide
      these.

PMID- 25949618
TI  - Attention deficit hyperactivity disorder (ADHD): review for primary care
      clinicians.
AB  - Attention deficit hyperactivity disorder (ADHD) is characterised by impulsivity,
      hyperactivity and inattention. Up to 5% of primary school age children have ADHD.
      Both genes and environment play a role in the aetiology of ADHD. If left
      untreated, children with ADHD demonstrate a range of poor long-term psychosocial
      outcomes. The Strengths and Difficulties Questionnaire (SDQ) may be used to
      screen children for a range of psychiatric disorders, including ADHD.(1)
      Principal management options include medication (methylphenidate and atomoxetine
      are the first line), parent training programmes and school based interventions.
      It is important to provide a dedicated child mental health specialist service for
      children with ADHD. In addition to following the National Institute for Health
      and Clinical Excellence (NICE) guidelines,(2) the authors recommend the use of
      wider systemic approaches and early intervention to optimise the effectiveness of
      recommended treatment options. 

PMID- 25949619
TI  - Use of psychotropics among looked after children: an audit in the Borough of
      Lambeth.
AB  - Background Looked after children and young people (LAC) have higher incidence of
      mental health problems than non-looked after children. Many mental health
      difficulties are missed in this group, in particular the effects of trauma and
      loss and the resulting depression. LAC often move between placements, which
      further disrupts their care and therapeutic interventions. NICE recommends that
      in most mental health disorders, children and adolescents should receive specific
      psychological therapies as first-line treatment, before medication. This standard
      should apply to LAC. Setting The audit was conducted in the Lambeth CLAMHS, a
      specialist mental health team working with LAC. Question To ascertain if Lambeth
      LAC (living in the borough) are receiving psychotropic medication without CLAMHS
      input and as their only treatment. (All LAC who are on psychotropic medication
      should have been offered psychological treatments first.) Methods A questionnaire
      was sent out to Lambeth general practice (GP) surgeries to find out what
      medications children were prescribed, if any. When children were prescribed
      psychotropic medication checks were made to ascertain whether they were receiving
      input from mental health services. Results LAC were seen in 67 different GP
      surgeries across Lambeth. Responses from 63 surgeries relating to 145 children
      (87.34% of the total number) were received. Conclusions There were no LAC in
      Lambeth who were prescribed psychotropic medication without a CAMHS service being
      involved. All the patients that were on psychotropic medication were known by
      CLAMHS or another child and adolescent mental health service within the South
      London and Maudsley NHS Foundation Trust. This is in accordance with NICE
      recommendations. 

PMID- 25949620
TI  - London AiT & First5 Committee: the voice of London General Practice Trainees
      within the Royal College of General Practitioners (RCGP).

PMID- 25949621
TI  - An account of my life.
AB  - This is the fifth instalment of the autobiography of John Horder. It was
      originally written for his grand-children to read. John is a founding father of
      modern general practice. He was doing his medical finals when the NHS was founded
      in 1948 and has been an active advocate of whole person, family and community
      oriented general practice ever since. He was one of the two founders of the
      Leeuwenhorst European Study Group that defined the job description of a general
      practitioner in 1974. He was President of the Royal College of General
      Practitioners between 1979 and 1982. He assisted the setting up of general
      practice educational bodies in several Western European countries, especially
      Yugoslavia and Portugal. He has been a tireless supporter of inter-disciplinary
      learning and founded the Centre for the Advancement of Inter-professional
      Education (CAIPE) in 1987. He lives in Primrose Hill with his wife Elizabeth
      June, who was also his partner in general practice. Abridged by Layla Stock
      (Ealing PCT). 

PMID- 25949623
TI  - Precious: a film based on the novel Push by Sapphire.

PMID- 25949624
TI  - Mother and child.

PMID- 25949622
TI  - A visit to the Foundling Museum.

PMID- 25949625
TI  - (Re)Organising and 'liberating' primary care.

PMID- 25949626
TI  - Primary care in an era of hospital bed reduction: what can we infer from QOF and
      PBC?
AB  - KEY MESSAGES: The Quality and Outcomes Framework (QOF) has been efficiently and
      effectively incorporated into practice routines. One possible negative effect of
      this has been a move towards a more biomedical form of practice.There has been
      patchy but real engagement with practice-based commissioning (PBC), with
      significant moves in some areas towards GPs acting collectively to improve
      services across the health economy, including engaging in performance management
      of each others' practice.Together, responses to QOF and PBC suggest that GPs may
      be willing and able to act both individually and collectively to try to mitigate
      the negative impacts of future spending reductions. WHY THIS MATTERS TO ME:
      General practice will be under a great deal of pressure in the next few years.
      Understanding the impact of past policy changes is essential if we are to ensure
      that the core values of general practice are maintained.

PMID- 25949628
TI  - Lord Howe interview.

PMID- 25949627
TI  - Public management 'reform' narratives and the changing organisation of primary
      care.
AB  - This paper explores how different models of public management affect the changing
      organisation of primary care. It examines important non-clinical drivers of major
      organisational change. It uses the concept of a 'reform narrative' to connect
      public management reform ideas, political doctrines and their effects on primary
      care organisations. It outlines a set of possible models of public management and
      their application with primary care settings. It explores what might be the
      dominant reform ideas of the next decade. 

PMID- 25949629
TI  - What have NHS managers ever done for us?
AB  - The image of the UK National Health Service manager has not always been positive.
      Like others in the public sector, NHS managers are sometimes associated in the
      media with waste and inefficiency, in contrast to those in 'front line roles'.
      Thus healthcare professionals and members of the public might ask, in the
      tradition of Monty Python's Life of Brian, what NHS managers have ever done for
      us. In this short article, we outline some of the evidence from the literature on
      attitudes to, and role of, healthcare managers, before drawing on our own
      interview and observation based fieldwork with managers themselves. We argue that
      the role of the healthcare manager is not always well understood, and that in a
      sector facing ever more intense and large scale organisational challenges,
      managers should be seen as important partners in a health service focused on
      clinical outcomes. 

PMID- 25949630
TI  - Patient safety: learning the lessons in primary care.
AB  - KEY MESSAGES: GPs are the champions of patient safety for their patients and have
      future possibility for driving patient safety across the entire health services.
      To fulfil this challenge clinicians need to consider how the techniques and tools
      widely applied in hospital care might best be used within primary care. This
      includes developing robust systems to effectively identify and capture
      information about safety events, procedures and collaborative activities to
      investigate and analyse safety event, and incentives and penalties for
      implementing safety improvements. WHY THIS MATTERS TO ME: Patient safety should
      be at the forefront of health-care. Primary care clinicians have the opportunity
      to drive this agenda in the future.

PMID- 25949631
TI  - The gold standard of management? Evidence-based management and healthcare
      delivery.
AB  - This article presents ideas from a current debate in the field of Management
      Studies, which suggests that healthcare organisations should take an evidence
      based approach to their management practice. Such arguments form part of a
      broader move toward the standardisation of knowledge and practice in healthcare
      organisations, and an overriding concern with organisational efficiency. However
      the complexity of healthcare decision-making and evidence-selection make this
      process problematic, including in primary care. 

PMID- 25949632
TI  - Inter-organisational communication for patients being case managed by community
      matrons.
AB  - Background Poor communication between community matrons (CMs), in-hours and out
      of-hours (OoH) general practitioners (GPs) causes uncertainty and inefficiencies.
      Setting A practice-based commissioning group in West London and the associated
      CMs who case manage high users of hospital services. Question What helps good
      communication between CMs, GPs and OoH services to ensure that the right patients
      are case managed and hospital admissions are avoided? Methods Whole system
      participatory action research, with four stages: 1) identify communication
      problems as perceived by a wide range of stakeholders; 2) draw a diagram of the
      existing communication system, and with stakeholders redraw this to overcome its
      weaknesses; 3) pilot the changes proposed; 4) gain consensus among stakeholders
      about policy. Results Stakeholders agreed that standards should be adopted to
      improve communication for the care of patients who are case managed by CMs.
      Routine passage of information between GP, CMs and the OoH services would achieve
      this, and is feasible. Specifically: routine information (termed Special Patient
      Notes) should be sent to the OoH service about vulnerable patients, including
      those who are case managed by CMsclear information about CM attachment to general
      practices and how to refer to them should be easily accessibleGPs and CMs should
      meet quarterly for mutual learning and to discuss patientsthe OoH service
      electronically should cascade information to GPs, CMs and others named in the
      Special Patient Notescommissioners should routinely gather data to compare
      clusters of general practices for i) referrals to CMs, ii) posting Special
      Patient Notes, iii) unscheduled consultations and hospital admissions of all
      patients including those being case managed. Discussion This project revealed
      system-wide communication problems for the care of patients being case managed by
      CMs, and ways to overcome these. Commissioners could insist that these are
      adopted locally, and gather data to prompt compliance and evaluate the
      consequential cost savings. 

PMID- 25949633
TI  - Oregon and the UK: experiments in resource allocation.
AB  - Decisions about how to spend money allocated to healthcare are complicated and
      merit a fully reasoned approach. Sources of moral justification for such
      decisions are examined and the innovative system engineered in the US state of
      Oregon described. Contrasts are drawn with the UK model and the conclusion is
      drawn that some public influence on such decisions is useful and should be
      explored. 

PMID- 25949634
TI  - Pam Chesters interview.

PMID- 25949636
TI  - An overview of the healthcare system in Taiwan.
AB  - Taiwan adopted a national health insurance system in 1995. It is a government
      administered insurance-based national healthcare system. Although, like the UK,
      Taiwan has a single payer system for healthcare, there are several differences
      between the two systems. The characteristics of the Taiwanese system include good
      accessibility, comprehensive population coverage, short waiting times, relatively
      low costs and a national health insurance databank for planning, monitoring and
      evaluating health services. The weaknesses include variable quality of care, a
      weak gatekeeper role and increasing financial pressures. 

PMID- 25949635
TI  - Healthcare needs personal doctors: a US perspective with British roots.

PMID- 25949637
TI  - An account of my life.
AB  - This is the sixth instalment of the autobiography of John Horder. It was
      originally written for his grandchildren to read. John is a founding father of
      modern general practice. He was doing his medical finals when the NHS was founded
      in 1948 and has been an active advocate of whole person, family and community
      oriented general practice ever since. He was one of the two founders of the
      Leeuwenhorst European Study Group that defined the job description of a general
      practitioner in 1974. He was President of the Royal College of General
      Practitioners between 1979 and 1982. He assisted the setting up of general
      practice educational bodies in several Western European countries, especially
      Yugoslavia and Portugal. He has been a tireless supporter of inter-disciplinary
      learning and founded the Centre for the Advancement of Inter-professional
      Education (CAIPE) in 1987. He lives in Primrose Hill with his wife Elizabeth
      June, who was also his partner in general practice. Abridged by Layla Stock
      (Ealing PCT). 

PMID- 25949638
TI  - Tales of two European cities: primary care in actualite.
AB  - Comparisons between primary care settings in Europe are of particular interest
      since the RCGP adopted EURACT criteria in the new MRCGP curriculum. This article
      contrasts two everyday GP experiences between Italy and England. Themes of
      practice are shown to be common but systemic differences are evident and prevail.
      The reader is encouraged to reflect on these two aspects in the course of the
      article. 

PMID- 25949639
TI  - Notes from Cuba: the importance of primary care.

PMID- 25949640
TI  - Could GP commissioning enable collaboration throughout the NHS?

PMID- 25949642
TI  - GP-led services for alcohol misuse: the Fresh Start Clinic.
AB  - Background A growing number of patients are presenting to health services with
      alcohol misuse disorders. The challenge to the NHS is to deliver the most cost
      effective treatment solutions for all forms of alcohol misuse disorders. Setting
      NHS Wandsworth undertook a 12-month pilot to identify the most effective model
      for delivering treatment for alcohol dependency within the primary care setting.
      Question What are the most effective models to treat patients with alcohol
      dependency in primary care? Methods Model A: This was a locally enhanced services
      agreement (LES) agreement for screening, brief interventions and treatment.
      Practices were required to attend training in the management of alcohol
      withdrawal and had access to specialist nurse support. Model B: A GP-led clinic
      supported by a full-time specialist nurse prescriber. The clinic was promoted as
      the Fresh Start Clinic. It offers planned alcohol withdrawal within a pre-agreed
      structured treatment plan, and sign posts to after care. Results There were 76
      treatment episodes in the fresh start clinic compared with 6 recorded treatment
      episodes under the LES. Fresh Start ClinicWaiting time to treatment is 7 days.We
      achieved a 100% completion rate.Patient satisfaction questionnaires confirmed
      positive patient experience.Twenty percent of patients completed
      questionnaires.Fifty seven percent abstinence at 3-6 months follow-up.Fifty
      percent improvement in mental well being as measured by Beck's Depression
      Inventory.Improvement in markers of dependency (GGT and MCV).The cost per
      treatment episode in the Fresh Start Clinic was significantly less. Conclusions
      The Fresh Start Clinic offers clinically safe and cost-effective treatment to
      patients suffering from mild to moderate alcohol dependency in a primary care
      setting and offers choice to both GP's and patients. 

PMID- 25949641
TI  - Opportunistic health checks in a retail environment.
AB  - Cardiovascular disease remains common and accounts for many deaths, but primary
      cardiovascular risk factors are consistently underdiagnosed in the UK. NHS health
      checks are being implemented nationally in the next five years, targeting those
      aged 40 to 74 years, and many primary care trusts have commissioned health checks
      to be carried out opportunistically as an outreach programme in public places to
      aid uptake and improve access. However, there is little published evidence on the
      effectiveness and subsequent follow-up rates in such a model. This service
      evaluation verifies the effectiveness of primary cardiovascular screening in a
      supermarket setting in south east London. Eight consecutive Saturday clinics were
      carried out at the entrance of a local supermarket offering opportunistic health
      screening including blood pressure, random glucose, body mass index and screening
      spirometry. The primary outcomes are rate of uptake of the service, the
      proportion of participants with previously undiagnosed cardiovascular risk
      factors that were identified from the screening, and the subsequent rate of
      follow-up. Over the eight-week period, 1024 participants (457 males, 44.6%; 567
      females 567, 55.4%) undertook the screening. Four hundred and twenty-two
      participants (41.2%) required follow-up for abnormal readings. Of these, 325
      (76.4%) were abnormal readings in participants with previously unknown disease
      (raised blood glucose, 95 participants (9.3%); raised blood pressure, 172
      participants (16.8%); FEV1 < 80%, 93 participants (9.1%)). Using the NHS health
      check age range, 34.3% of raised blood pressure measurements and 38.9% of raised
      blood glucose measurements would not have been picked up. The cost per patient
      was L19, the cost per abnormal finding was L43.66. Opportunistic health screening
      targeting particular groups of individuals appears to be highly effective in
      identifying significant pathology. The main limitation of this pilot was that
      cholesterol measurement was not performed and therefore full cardiovascular risk
      assessment could not be offered. 

PMID- 25949643
TI  - Integrated musculoskeletal service design by GP consortia.
AB  - Background Musculoskeletal conditions are common in primary care and are
      associated with significant co-morbidity and impairment of quality of life.
      Traditional care pathways combined community-based physiotherapy with GP referral
      to hospital for a consultant opinion. Locally, this model led to only 30% of
      hospital consultant orthopaedic referrals being listed for surgery, with the
      majority being referred for physiotherapy. The NHS musculoskeletal framework
      proposed the use of interface services to provide expertise in diagnosis, triage
      and management of musculoskeletal problems not requiring surgery. The White Paper
      Equity and Excellence: Liberating the NHS has replaced PCT commissioning with GP
      consortia, who will lead future service development. Setting Primary and
      community care, integrated with secondary care, in the NHS in England. Question
      How can GP consortia lead the development of integrated musculoskeletal services?
      REVIEW: The Ealing experience We explore here how Ealing implemented a 'See and
      Treat' interface clinic model to improve surgical conversion rates, reduce
      unnecessary hospital referrals and provide community treatment more efficiently
      than a triage model. A high-profile GP education programme enabled GPs to triage
      in their practices and manage patients without referral. Conclusion In Ealing, we
      demonstrated that most patients with musculoskeletal conditions can be managed in
      primary care and community settings. The integrated musculoskeletal service
      provides clear and fast routes to secondary care. This is both clinically
      effective and cost-effective, reserving hospital referral for patients most
      likely to need surgery. GP consortia, in conjunction with strong clinical
      leadership, inbuilt organisational and professional learning, and a GP champion,
      are well placed to deliver service redesign by co-ordinating primary care
      development, local commissioning of community services and the acute
      commissioning vehicles responsible for secondary care. The immediate priority for
      GP consortia is to develop a truly integrated service by facilitating consultant
      opinions within a community setting.

PMID- 25949644
TI  - The role of research in helping general practice commission efficient healthcare.
AB  - The new commissioning consortia face a major challenge in improving the
      efficiency of the NHS. They are new organisations, and at the same time as
      establishing themselves they need to overcome significant obstacles to reforming
      services. Research evidence about the value of care can help consortia achieve
      efficiencies, but there are often delays between the provision of evidence and
      its routine use in policy and practice. The National Institute for Health
      Research (NIHR) has invested substantial funding in providing evidence for the
      NHS, and in this article we discuss how consortia can make sure they obtain and
      apply relevant evidence as quickly as possible, and also generate evidence on
      practical questions such as the impact of redesigned services. Partnership with
      NIHR research organizations, particularly the Collaborations for Leadership in
      Applied Research and Care (CLAHRCs), offer one approach to helping consortia
      commission efficient health care.

PMID- 25949645
TI  - Simulating the impact of change: implementing best practice in stroke care.
AB  - This article presents the experience of healthcare decision-makers who used
      simulation to better understand the impact of adopting best practice in stroke
      care, as outlined in the National Stroke Strategy. It describes the process of
      developing a simulation model and how stakeholders were involved in testing the
      key questions, which they needed to answer in order to adopt a new commissioning
      strategy for stroke care. It outlines what simulation is and discusses how it can
      be used to support evidenced-based decision-making. 

PMID- 25949646
TI  - Using routinely gathered data to evaluate locally led service improvements.
AB  - Background Between 2009 and 2010 NHS Ealing tested the feasibility of a)
      combining data from more than one data-domain at the same time to quantify
      patient movement across the primary care/acute hospital boundary, and b)
      establishing online analyses so they can be constantly updated with near real
      time data to compare different subsets of patients. The reports allowed us to
      see: changes in hospital admissions before and after referral to community
      matrons of patients with complex conditions from one practice-based commissioning
      (PBC) groupchanges in hospital bed-days of all patients from one practice or PBC
      group during a complex intervention designed to assist inter-disciplinary
      collaboration. Results The teams leading the projects found that the reports gave
      them confidence in the projects and helped to influence local policy. Discussion
      GP consortia need to evaluate complex service improvements in order to contain
      costs and improve quality. They will find such reports helpful to give ongoing
      feedback and this may help to keep people engaged. Present plans for data
      warehousing in London do not have this ability - they do not combine data from
      across the whole health economy, and are focused either on claims validation or
      risk stratification. 

PMID- 25949647
TI  - Patient record access: making it work for you and the NHS.
AB  - Background Patient record access is NHS policy. It is now a reality in the UK,
      although it remains a rarity. Setting This article summarises the current state
      of patient record access in the UK, focusing on a particular system for which
      there is most data available. It also explores possibilities for expanded
      functionality in the near future. This will offer both patients and the NHS a
      more interactive approach that offers significant benefits to both. Results
      Patient record access not only appears safe, but also offers benefits to
      patients. These include improved safety; a more accurate record; better
      relationships between patients and clinicians; better data sharing and
      integration across the NHS; improved self-care and shared decision-making; and
      better compliance. Practices gain by saving time. In addition, they gain by
      having empowered patients who can do more for themselves. However, clinicians in
      general, and GPs in particular, are anxious about enabling record access, fearing
      loss of control, litigation and breaches of the daa protection act. Conclusions
      Patient record access with added transactional services is likely to benefit
      patients and practices across the NHS. It supports QIPP. It is likely to become
      routine, but cannot substitute for good traditional communication with and
      support for patients. 

PMID- 25949648
TI  - What would an ideal mental health service for primary care look like?
AB  - The creation of GP commissioning consortia offers potential opportunities for GPs
      to challenge a number of divisions and distinctions that are currently taken for
      granted in mental health services, but may be neither necessary nor logical. I
      examine a range of these and suggest what GPs and patients might reasonably
      expect if we challenged them in order to imagine and commission an ideal mental
      health service for primary care. Among its features, an ideal service would cross
      the boundaries of mental and physical care, individual and family care, and the
      mental, social and economic domains. It would also transcend mental health
      ideologies, geographical borders and the artificial distinction between making a
      diagnosis, offering treatment and holding a therapeutic conversation. 

PMID- 25949649
TI  - Making a jigsaw puzzle in 10 minutes: is case management feasible in general
      practice?
AB  - Background Case management has been advocated as a method of optimising the care
      of patients with complex problems and reducing inappropriate use of hospital
      services, but its impact to date has been limited. It is not known whether case
      management earlier in the development of complex problems will be more effective.
      Aim To develop a case management protocol usable in general practice. Design Co
      designed by practitioners using a technology development approach. Setting
      General practices and community nursing teams in one primary care trust (PCT).
      Method Nominal group techniques applied to six multidisciplinary workshops held
      over nine months, in order to design and refine a case management protocol. Then
      field testing of the protocol with selected patients in four practices. Results A
      modular case management protocol has been designed that can be used in routine
      practice and completed over successive consultations. The protocol asks the
      practitioner and patient about their different perspectives on need, and about
      mental health, social care needs, nutritional status, vision and hearing, bone
      fragility, pain, continence and where appropriate end-of-life plans. An
      electronic version can be partially populated automatically, from the existing
      medical record. Field testing suggests that a paper version can also be used as a
      patient-held record for other professionals to use. Conclusion This study has
      created a model of case management for general practice that appears to be
      useable in general practice. A wider feasibility study is now needed to test
      uptake of the protocol by practices. 

PMID- 25949650
TI  - The old care paradigm is dead, long live the new sustainable care paradigm: how
      can GP commissioning consortia meet the demand challenges of 21st century
      healthcare?
AB  - There are many challenges facing the health system in the 21st century - the
      majority of which are related to managing demand for health services. To meet
      these challenges emerging GP commissioning consortia will need to take a new
      approach to commissioning health services - an approach that moves beyond the
      current acute-centred curative paradigm of care to a new sustainable paradigm of
      care that focuses on primary care, integrated services and upstream prevention to
      manage demand. A key part of this shift is the recognition that the health system
      does not operate in a vacuum and that strategic commissioning decisions must take
      account of wider determinants of health and well-being, and operate within the
      finite limits of the planet's natural resources. The sustainable development
      principle of balancing financial, social and environmental considerations is
      crucial in managing demand for health services and ensuring that the health
      system is resilient to risks of resource uncertainty and a changing climate.
      Building sustainability into the governance and contracting processes of GP
      commissioning consortia will help deliver efficiency savings, impact on system
      productivity, manage system risk and help manage demand through the health co
      benefits of taking a whole systems approach to commissioning decisions.
      Commissioning services from providers committed to corporate social
      responsibility and sustainable business practices allows us to move beyond a
      health system that cures people reactively to one in which the health of
      individuals and populations is managed proactively through prevention and
      education. The opportunity to build sustainability principles into the culture of
      GP commissioning consortia upfront should be seized now to ensure the new model
      of commissioning endures and is fit for the future. 

PMID- 25949651
TI  - Ethics of the ordinary: a meeting run by the Royal Society of Medicine with the
      Royal College of General Practitioners.

PMID- 25949653
TI  - Working in partnership across London: RCGP London.

PMID- 25949652
TI  - Everyday ethics: learning from an 'ordinary' consultation in general practice.
AB  - The author uses a constructed case to analyse some of the ethical decisions that
      UK general practitioners face in everyday settings. A variety of ethical
      frameworks and empirical primary healthcare literature are used to demonstrate
      how ethical tools may be used by clinicians in primary healthcare to reflect on
      their decisions in practice. The GP consultation context can make 'on the spot'
      ethical decisions difficult and varied. 

PMID- 25949655
TI  - You shouldn't go talking like that doctor.

PMID- 25949654
TI  - An account of my life.
AB  - This is the seventh instalment of the autobiography of John Horder. It was
      originally written for his grandchildren to read. John is a founding father of
      modern general practice. He was doing his medical finals when the NHS was founded
      in 1948 and has been an active advocate of whole person, family and community
      oriented general practice ever since. He was one of the two founders of the
      Leeuwenhorst European Study Group that defined the job description of a general
      practitioner in 1974. He was president of the Royal College of General
      Practitioners between 1979 and 1982. He assisted the setting up of general
      practice educational bodies in several western European countries, especially
      Yugoslavia and Portugal. He has been a tireless supporter of inter-disciplinary
      learning and founded the Centre for the Advancement of Inter-professional
      Education (CAIPE) in 1987. He lives in Primrose Hill with his wife Elizabeth
      June, who was also his partner in general practice. Abridged by Layla Stock
      (Ealing PCT). 

PMID- 25949656
TI  - Body and mind entwined: an 11-year-old perspective on 'things'.

PMID- 25949657
TI  - The book of death: weighing your heart.

PMID- 25949658
TI  - London journal of primary care: stage two.

PMID- 25949659
TI  - What kind of leadership does integrated care need?
AB  - Primary care clinicians and clinical commissioners are the current focus for much
      leadership investment and development. In this article I propose that we need to
      look beyond traditional thinking about effective leader behaviour and
      conventional approaches to leader development based on this thinking. The paper
      identifies some of the lessons that can be learnt from both the current academic
      discussion of collaborative leadership, and from an analysis of successes and
      failures of leadership within the NHS. Two leadership strategies are considered:
      the development of communities of practice and the use of connected mini
      transformations to generate wider system transformation. In a period of systems
      change, with potential for conflict between providers and commissioners, these
      strategies are helpful in encouraging the 'mindfulness' that is needed to ensure
      integration across the complex landscape of healthcare in London. 

PMID- 25949660
TI  - The integrated care pilot in north west london.
AB  - In 2011-2012 partners in the provision of health in social care came together in
      North West London from five local authorities, two major acute trusts, two
      community trusts, two mental health trusts, two 'third sector' organisations and
      over 100 general practices. Their aim was to support collaborative working in
      geographic areas of about 50 000 population for improved patient experience,
      quality of outcomes and cost-efficiency. Patients with diabetes and those over 75
      were targeted with care plans and locally-led innovation. Through monthly
      workshops practitioners from different organisations shared their insights into
      ways to improve care for specific individuals and also to improve the functioning
      of the system as a whole. The pilot is still under review and evaluation but has
      produced some positive results so far both in patient and clinician experience
      and the suggestion that this way of working results in reduced emergency
      admissions to hospital. 

PMID- 25949661
TI  - Achieving University Linked Localities through Health Networks.

PMID- 25949662
TI  - What's new?

PMID- 25949663
TI  - Integration in stroke services: the challenges for primary and community care
      services.
AB  - Objectives A number of evidence-based interventions are now available for stroke
      patients. Good quality stroke care involves a range of health professionals
      located across ambulance, hospital, community and primary care services. This
      study examined the perspectives of healthcare workers involved in stroke care in
      two different English case study sites on the integration challenges stroke care
      presents. Methods Two qualitative case studies were carried out, including 45
      semi-structured interviews with clinicians and managers associated with two
      different hospitals providing specialised stroke services. Findings High levels
      of organisational, functional, service and clinical integration amongst
      clinicians that deliver emergency and acute stroke care were identified. This is
      frequently lacking amongst professionals delivering post-acute care. These
      findings are linked to the prevalence or lack of normative and systemic
      integration in each respective stage of care. Conclusions Emphasis on the need to
      treat stroke as an emergency condition in England over recent years has created a
      context in which normative and systemic integration often occurs amongst
      clinicians that deliver emergency and acute stroke care, aiding the development
      of organisational, functional, service and clinical integration across the case
      study sites. In contrast, integration between hospital and community
      (rehabilitation and general practice) care is frequently less successful. 

PMID- 25949664
TI  - Integrated Cancer System: a perspective on developing an integrated system for
      cancer services in London.
AB  - This article explores the potential for integrated cancer systems to improve the
      quality of care and deliver cost efficiencies and improve outcomes for cancer
      patients. Currently, patients in the UK still have poorer survival rates than
      comparable countries such as Canada, Sweden, Norway and Australia. Improving the
      quality of cancer services is a key policy objective and cancer is a priority
      outcome measure in both the NHS and Public Health Outcomes Framework. Evidence
      suggests that better integrated delivery has the potential to improve the quality
      and reduce the cost of healthcare, and ultimately improve health outcomes. One of
      the key themes from the Model of Care for Cancer Services (1) was that cancer
      services should be commissioned along pathways and that provider networks should
      be established to deliver care. London has two integrated cancer systems; one
      covering north central and east London (London Cancer) and the other covering
      west and south London (London Cancer Alliance). There a number of areas in cancer
      care that the current model of service provision has failed to adequately address
      and which have the potential to improve significantly though implementation of
      integrated services. These include improving early diagnosis, reducing
      inequalities in access to treatment and outcomes and maximising research and
      training across the system. Important drivers for the integration of cancer
      services are strong clinical leadership, shared informatics systems, focusing on
      quality of services and improving patient experience. Emerging needs of
      integrated cancer in London are around strengthening the involvement of primary
      care, public health and the third sector; working to develop sufficient capacity
      and expertise in primary care and collaborating more closely with commissioners
      to develop integrated systems. 

PMID- 25949665
TI  - Barriers to the implementation of self management support in long term lung
      conditions.
AB  - Background Self-management improves outcomes in asthma and COPD and is strongly
      recommended in national and international guidelines; however implementation of
      the guidelines such as use of written action plans in practice is often poor.
      Setting A questionnaire survey was undertaken to identify the healthcare
      professional barriers to implementation of self-management for asthma and COPD in
      West London. Question Why is self-management education not being undertaken in
      respiratory conditions? Methods A questionnaire was designed to elicit healthcare
      professionals' views about barriers to implementation of self-management in
      asthma and COPD. Results Response rates were 33% (58/175). Results showed strong
      support for guideline recommendations, however implementation was patchy. Seventy
      six percent of respondents discussed asthma self-management with patients;
      however only 47.8% of patients received a written action plan. For COPD patients,
      55.1% discussed self-management, with 41% receiving a written action plan. In
      COPD, there was greater GP involvement and less delegation of self-management.
      Barriers to implementation included patient factors (compliance, literacy and
      patient understanding), time constraints and insufficient resources. Those who
      believed they had witnessed improved health outcomes with self-management (53%,
      31/58) were more likely to give written action plans (78%, 24/31, 'nearly
      always/sometimes' gave written action plans), Nearly a third of healthcare
      professionals reported lacking confidence in constructing written action plans
      (33% 19/58; GPs 43%, nurses 43%). Conclusion Despite overwhelming evidence self
      management support is still not being implemented into routine clinical practice,
      identified barriers included time constraints, lack of training, lack of belief
      in patients ability to self-manage and lack of confidence completing self
      management plans. Practice implications These issues need to be addressed if self
      management support is to be delivered in a meaningful and effective way. 

PMID- 25949666
TI  - Reflections on charles dickens.

PMID- 25949667
TI  - Educating for integrated care.

PMID- 25949668
TI  - Educating for integrated care.
AB  - In September 2012 the North West London Integrated Care Plot held a conference
      for clinical educators. The aim was to reach a consensus about what learning
      clinical staff needed in order to contribute to an integrated care system. The
      conference was attended by 81 clinical educators from a range of backgrounds. The
      participants decided that competence in the following three domains was
      essential: 1. Patient and user engagement and empowerment. 2. Collaboration with
      other health and social care professionals. 3. Leading improvement in the system
      of care. Educational interventions to facilitate learning should wherever
      possible be interprofessional, team based and experiential. The views of
      patients, carers and users should inform the education. Assessment should take
      into account real-life performance through multi-source feedback and observed
      practice. Evaluation of the educational intervention should take into account any
      impact on the patient and user experience as well as clinical outcome measures. 

PMID- 25949669
TI  - Engaging patients, users and carers in integrated care.
AB  - Engaging patients, users and carers is an important enabler of integrated care.
      We describe how the Inner North West London Integrated Care Pilot set up a
      Patients, Users and Carers Committee, found volunteers to join it, and and helped
      to prepare them for their role. Representatives from the group were included in
      the membership of the Pilot's management board and committees and took part in
      several engagement and educational events. Some obstacles and challenges were
      encountered, including communicating with a large number of patient participation
      groups across the area, managing the high expectations of the group about how
      quickly reforms could be achieved, and ensuring that members of other committees
      understood the role of the representatives. Benefits included easy access to the
      perspectives of patients, users and carers when developing the strategy, policies
      and processes of the Pilot. Representatives proved to be eloquent advocates, and
      played a part in the success of the Pilot in winning some prestigious awards. 

PMID- 25949670
TI  - Learning from the integrated care pilot in west london.
AB  - KEY MESSAGES: We implemented a system to integrate care for patients with
      diabetes and/or over the age of 75 in an urban area with a population of 1.2
      million. Within five months, all the acute, mental health and community trusts,
      and all the local authorities had signed up to participate, along with 84% of GP
      practices in the area. Patients and practitioners found the system of benefit in
      improving communication and collaboration. The first phase of the Outer North
      West London Integrated Care Pilot (ONWL ICP) has shown that it is possible to
      implement large-scale, multi-agency change in a short time to enable coordinated
      care for patients with long-term conditions.The second phase needs to more
      purposefully integrate with local programmes of work, including training the
      chairs of the monthly case conferences as leaders of transformational change who
      can lead annual cycles of interorganisational continuous quality improvement. WHY
      THIS MATTERS TO US: We are clinicians and managers who have been closely involved
      in the planning and implementation of the integrated care system described here.
      We feel that current systems are fragmented and do not support delivery of
      holistic, coordinated care. We are convinced of the benefits of multiple agencies
      working together to share their expertise of patients' social, psychological and
      physical needs.

PMID- 25949671
TI  - How important is mental health involvement in integrated diabetes care? The Inner
      North West London experience.
AB  - Supported self-management is key to good diabetes care, but the high rates of
      mental health difficulties in diabetes can hinder effective self-management.
      Depression, anxiety, eating disorders and cognitive impairment, as well as
      interpersonal difficulties and personality disorder are all known to have a
      detrimental effect on effective self-care and addressing these has been
      demonstrated to improve health and financial outcomes. We propose that
      integrating mental health into the core of diabetes care is vital to improve
      detection and effective treatment rates of these disorders as well as improving
      confidence of all professionals who support people living with diabetes. We found
      that in 81% of all cases brought to the multidisciplinary complex case
      conferences, mental health issues were discussed. The majority of these were
      regarding reasons for people not effectively self-managing their diabetes despite
      having education on diabetes. We found that there was a demand for our input in
      case conferences, educational sessions about self-management, cognition, capacity
      and mental illness, and a need and demand for a specialist mental health diabetes
      service. 

PMID- 25949672
TI  - Three care plans from one West London multidisciplinary group workshop.
AB  - This section of LJPC provides multidisciplinary insights into ways in which to
      explore the problems of patients, particularly those with long-term conditions.
      Each case presented must have had multidisciplinary discussions to arrive at a
      management plan. To retain patient anonymity the specific location of the case
      study must not be mentioned and details that might identify specific individuals
      should be altered. When submitting papers to this section your covering letter
      should explain which bits have been altered. Each case should be structured as
      follows: The Problem(s) as perceived by the clinician presenting the case;The
      Story-a brief summary of the history and context;Suggestions made by team members
      about ways to think about the problem(s);Action Points, including data to be
      gathered by the clinician to explore the approach to the problem; andA Review
      (where done)-of what happened. Authors are encouraged to complete this section at
      a later date including what they learned. The Editor for this section of LJPC is
      Dr Senan Devendra, Consultant Physician in Acute Medicine & Endocrinology, West
      Hertfordshire Hospitals NHS Trust. Email: ddevendra@nhs.net. 

PMID- 25949673
TI  - What can health and wellbeing boards do for us?

PMID- 25949675
TI  - How Ealing Health Networks can contribute to efficient and quality healthcare.
AB  - We describe how the formation of Health Networks in Ealing leads to improved
      outcomes for patients by the coordination of the care they receive by health and
      social care professionals. 

PMID- 25949674
TI  - Health and Wellbeing Boards for a new public health.
AB  - We remind readers of the evidence that community empowerment is a cost-effective
      way to improve health, and also that the conditions now exist to develop this
      approach in the UK, by facilitating collaboration between clusters of general
      practices and multiple other organisations. We argue that it is the role of
      Health and Wellbeing Boards to make sure that this huge potential is realised. 

PMID- 25949676
TI  - Taking diabetes services out of hospital into the community.
AB  - We describe four stages of an initiative to co-create a shared care system to
      treat patients with diabetes out of hospital and in the community. 

PMID- 25949678
TI  - Recipes for collaborative practice improvement and community development for
      health.

PMID- 25949677
TI  - Using routinely gathered data to empower locally led health improvements.
AB  - Data are routinely used throughout the NHS to report on and monitor performance.
      For example, detailed information regarding hospital episodes is reported via the
      Secondary Use Services (SUS) programme. Local commissioners use this data to
      monitor hospital contracts. In primary care, data such as glycaemic control of
      diabetes patients is extracted from general practice clinical systems to
      calculate practice payments for the 'Quality and Outcomes Framework' (QOF). We
      suggest that this routinely gathered data should also be used to help clusters of
      practices to learn from locally led innovation and to motivate long-term
      partnerships for interorganisational health improvement. Following the recent NHS
      reforms, the number of data sources that could facilitate this is likely to
      increase in size, variety and complexity. In this paper, we describe some of the
      existing data sources that could be used to do this; we also describe some of the
      dangers of using data in this way, and our conclusions about the best way
      forward. 

PMID- 25949679
TI  - The emergence of new forms for education and health fit for the challenges of the
      21st century.

PMID- 25949680
TI  - InterWell: an integrated school-based primary care model.
AB  - The Intergenerational School is an innovative, high-performing public school in
      Cleveland, Ohio that fosters lifelong learning and individual and community
      health. Narrative approaches, information technology enhancements, art and music
      enrichments, and nature-based programming foster brain health in the service of
      purposeful and healthy living in the community. A newly designed integrated
      primary and public healthcare model, called InterWell, which is planned to be
      based in the school, has the potential to transform conceptions and practices of
      health. Interprofessional care supporting chronic disease self-management and
      transdisciplinary research are foundational to our model. Over the 13-year
      history of the school, barriers to acceptance of this model of education and
      health have been reduced and greater community support engendered, but challenges
      of priorities and funding remain. Can this new model help support human
      flourishing in this time of global ecological and social disruption? 

PMID- 25949681
TI  - The Lime Tree School endeavour: healthy body, brain and heart.
AB  - Imagine what fun pupils would have at a school where the head dresses up as
      Dennis the Menace for World Book Day? And equally beneficial to the school, where
      parents can achieve a sustainable win-win by donating unwanted clothing, which is
      then sold to recyclers to boost school funds? These are the values that sustain
      Lime Tree Primary, Kingston's newest school which opened its doors in September
      2012. Central to the school's ethos is the unique partnership between health and
      education that has transformed this fledgling primary school into a real
      community asset. The problem was a real one facing many local authorities today:
      a rising birth rate and too few classroom places; a new build seemed the obvious
      solution - and a real opportunity. Local children, their families, residents and
      professionals were interviewed and their ideas translated into proposals for the
      new school. A magical learning environment for local youngsters was created,
      embodied by the school motto, which recognises that a healthy body sustains
      better learning, and better learning leads to enhanced health benefits. The
      school lives and breathes 'Healthy Body, Brain and Heart' and transfers this into
      all its daily activities. And what of the future? There is no doubt that this
      type of initiative could be adopted in other parts of the new NHS. Wouldn't it be
      marvellous if other examples of like collaboration could help us jointly tackle
      the challenges of modern-day living? 

PMID- 25949682
TI  - The adventurous school.
AB  - This paper describes three schools that worked with their local communities to
      create opportunities for their children to learn how to be skillful adventurers
      in our complex and ever-changing world. Each involved learners fully in their
      learning, clarifying what learning means and enabling it to happen through real
      and purposeful experiences. Each worked proactively with their communities and
      took local control of designing and developing the curriculum. 

PMID- 25949683
TI  - Interprofessional communication for adults who need multiple agency input.

PMID- 25949684
TI  - Out-of-hours special patient notes.
AB  - In 2011, an out-of-hours service in central London reviewed its system for
      special patient notes (SPNs) - a main mechanism to communicate valuable
      information about patients to the clinicians who cover two-thirds of the week
      when day-time general practices are closed. This revealed that: half of frequent
      callers did not have an SPNabout half of existing SPNs were out of dateday-time
      general practitioners (GPs) respond well to requests by out-of-hours doctors to
      provide an SPNproviding SPNs was low on the list of priorities of day-time GPs
      who were too busy reacting to everyday problems. 

PMID- 25949686
TI  - Coordinate My Care from the perspective of the London Ambulance Service.

PMID- 25949685
TI  - Electronic palliative care co-ordination system: an electronic record that
      supports communication for end-of-life care - a pilot in Richmond, UK.
AB  - Most people prefer to die at home, however, the majority die in an acute
      hospital. Supporting a patient in their preferred place of care may be aided by
      exchange of information across sectors. Richmond piloted an electronic palliative
      care coordination system (EPaCCS) to enhance interprofessional communication for
      end-of-life care. One such EPaCCS is the Coordinate My Care (CMC) hosted by the
      Royal Marsden NHS Foundation Trust, now supported across London. It focused
      clinicians on having advance care planning conversations with patients and their
      carers and then documenting the outcome onto an electronic web-based record that
      can be shared with key healthcare professionals. 

PMID- 25949687
TI  - Sharing electronic records: separating out the signals from ethical white noise.
AB  - The development of shared electronic records has been galvanised by initiatives
      to improve the information technology infrastructure of healthcare and by
      fragmentation of healthcare provision. This report uses a public discussion by
      the RCGP Ethics Committee, Patient Participation Group and the Informatics Group
      to review key issues relating to shared electronic healthcare records. These
      records may be a social necessity, and ethical and legal safeguards may allay
      some public and professional anxiety about their appropriate use. Many of the
      specific ethical concerns, such as confidentiality of healthcare information, are
      not new but how these concerns arise in context may be. Function creep was a key
      concern in the discussion. 

PMID- 25949688
TI  - What can health and wellbeing boards do for us?

PMID- 25949690
TI  - How Ealing Health Networks can contribute to efficient and quality healthcare.
AB  - We describe how the formation of Health Networks in Ealing leads to improved
      outcomes for patients by the coordination of the care they receive by health and
      social care professionals. 

PMID- 25949689
TI  - Health and Wellbeing Boards for a new public health.
AB  - We remind readers of the evidence that community empowerment is a cost-effective
      way to improve health, and also that the conditions now exist to develop this
      approach in the UK, by facilitating collaboration between clusters of general
      practices and multiple other organisations. We argue that it is the role of
      Health and Wellbeing Boards to make sure that this huge potential is realised. 

PMID- 25949692
TI  - Using routinely gathered data to empower locally led health improvements.
AB  - Data are routinely used throughout the NHS to report on and monitor performance.
      For example, detailed information regarding hospital episodes is reported via the
      Secondary Use Services (SUS) programme. Local commissioners use this data to
      monitor hospital contracts. In primary care, data such as glycaemic control of
      diabetes patients is extracted from general practice clinical systems to
      calculate practice payments for the 'Quality and Outcomes Framework' (QOF). We
      suggest that this routinely gathered data should also be used to help clusters of
      practices to learn from locally led innovation and to motivate long-term
      partnerships for interorganisational health improvement. Following the recent NHS
      reforms, the number of data sources that could facilitate this is likely to
      increase in size, variety and complexity. In this paper, we describe some of the
      existing data sources that could be used to do this; we also describe some of the
      dangers of using data in this way, and our conclusions about the best way
      forward. 

PMID- 25949691
TI  - Taking diabetes services out of hospital into the community.
AB  - We describe four stages of an initiative to co-create a shared care system to
      treat patients with diabetes out of hospital and in the community. 

PMID- 25949693
TI  - Recipes for collaborative practice improvement and community development for
      health.

PMID- 25949694
TI  - The emergence of new forms for education and health fit for the challenges of the
      21st century.

PMID- 25949695
TI  - InterWell: an integrated school-based primary care model.
AB  - The Intergenerational School is an innovative, high-performing public school in
      Cleveland, Ohio that fosters lifelong learning and individual and community
      health. Narrative approaches, information technology enhancements, art and music
      enrichments, and nature-based programming foster brain health in the service of
      purposeful and healthy living in the community. A newly designed integrated
      primary and public healthcare model, called InterWell, which is planned to be
      based in the school, has the potential to transform conceptions and practices of
      health. Interprofessional care supporting chronic disease self-management and
      transdisciplinary research are foundational to our model. Over the 13-year
      history of the school, barriers to acceptance of this model of education and
      health have been reduced and greater community support engendered, but challenges
      of priorities and funding remain. Can this new model help support human
      flourishing in this time of global ecological and social disruption? 

PMID- 25949697
TI  - The adventurous school.
AB  - This paper describes three schools that worked with their local communities to
      create opportunities for their children to learn how to be skillful adventurers
      in our complex and ever-changing world. Each involved learners fully in their
      learning, clarifying what learning means and enabling it to happen through real
      and purposeful experiences. Each worked proactively with their communities and
      took local control of designing and developing the curriculum. 

PMID- 25949696
TI  - The Lime Tree School endeavour: healthy body, brain and heart.
AB  - Imagine what fun pupils would have at a school where the head dresses up as
      Dennis the Menace for World Book Day? And equally beneficial to the school, where
      parents can achieve a sustainable win-win by donating unwanted clothing, which is
      then sold to recyclers to boost school funds? These are the values that sustain
      Lime Tree Primary, Kingston's newest school which opened its doors in September
      2012. Central to the school's ethos is the unique partnership between health and
      education that has transformed this fledgling primary school into a real
      community asset. The problem was a real one facing many local authorities today:
      a rising birth rate and too few classroom places; a new build seemed the obvious
      solution - and a real opportunity. Local children, their families, residents and
      professionals were interviewed and their ideas translated into proposals for the
      new school. A magical learning environment for local youngsters was created,
      embodied by the school motto, which recognises that a healthy body sustains
      better learning, and better learning leads to enhanced health benefits. The
      school lives and breathes 'Healthy Body, Brain and Heart' and transfers this into
      all its daily activities. And what of the future? There is no doubt that this
      type of initiative could be adopted in other parts of the new NHS. Wouldn't it be
      marvellous if other examples of like collaboration could help us jointly tackle
      the challenges of modern-day living? 

PMID- 25949698
TI  - Interprofessional communication for adults who need multiple agency input.

PMID- 25949700
TI  - Electronic palliative care co-ordination system: an electronic record that
      supports communication for end-of-life care - a pilot in Richmond, UK.
AB  - Most people prefer to die at home, however, the majority die in an acute
      hospital. Supporting a patient in their preferred place of care may be aided by
      exchange of information across sectors. Richmond piloted an electronic palliative
      care coordination system (EPaCCS) to enhance interprofessional communication for
      end-of-life care. One such EPaCCS is the Coordinate My Care (CMC) hosted by the
      Royal Marsden NHS Foundation Trust, now supported across London. It focused
      clinicians on having advance care planning conversations with patients and their
      carers and then documenting the outcome onto an electronic web-based record that
      can be shared with key healthcare professionals. 

PMID- 25949699
TI  - Out-of-hours special patient notes.
AB  - In 2011, an out-of-hours service in central London reviewed its system for
      special patient notes (SPNs) - a main mechanism to communicate valuable
      information about patients to the clinicians who cover two-thirds of the week
      when day-time general practices are closed. This revealed that: half of frequent
      callers did not have an SPNabout half of existing SPNs were out of dateday-time
      general practitioners (GPs) respond well to requests by out-of-hours doctors to
      provide an SPNproviding SPNs was low on the list of priorities of day-time GPs
      who were too busy reacting to everyday problems. 

PMID- 25949701
TI  - Coordinate My Care from the perspective of the London Ambulance Service.

PMID- 25949702
TI  - Sharing electronic records: separating out the signals from ethical white noise.
AB  - The development of shared electronic records has been galvanised by initiatives
      to improve the information technology infrastructure of healthcare and by
      fragmentation of healthcare provision. This report uses a public discussion by
      the RCGP Ethics Committee, Patient Participation Group and the Informatics Group
      to review key issues relating to shared electronic healthcare records. These
      records may be a social necessity, and ethical and legal safeguards may allay
      some public and professional anxiety about their appropriate use. Many of the
      specific ethical concerns, such as confidentiality of healthcare information, are
      not new but how these concerns arise in context may be. Function creep was a key
      concern in the discussion. 

PMID- 25949703
TI  - Introducing Volume 6 of London Journal of Primary Caer: community-oriented
      integrated care.

PMID- 25949704
TI  - Going with the grain: organising for a purpose.
AB  - In looking at reform, it is important to understand the longer heritage of the
      public sector. This suggests a future drawing on mutual ideas and principles as a
      powerful alternative to private ownership. It involves a new approach to
      organisational design which underpins a reformed service delivery model. This is
      examined through the example of Rochdale Boroughwide Housing, the UK's first
      mutual social housing provider, owned and controlled by its tenant and employee
      members. 

PMID- 25949705
TI  - The impact of patient record access on appointments and telephone calls in two
      English general practices: a population-based study.
AB  - Background Government policy expects all patients who wish to have online record
      access (RA) by 2015. We currently have no knowledge of the impact of patient
      record access on practice workload. Setting Two urban general practices in
      Manchester. Question What is the impact of patient RA on telephone calls and
      appointments in UK general practice? Method We asked patients in two urban
      general practices who used RA whether it had increased or decreased their use of
      the practice over the previous year. Using practice data, we calculated the
      change in appointments, telephone calls and staff cost. We also estimated the
      reduction in environmental costs and patient time. Results An average of 187
      clinical appointments (of which 87 were with doctors and 45 with nurses) and 290
      telephone calls were saved. If 30% of patients used RA at least twice a year,
      these figures suggest that a 10 000-patient practice would save 4747 appointments
      and 8020 telephone calls per year. Assuming a consultation rate of 5.3% annually,
      that equates to a release of about 11% of appointments per year, with significant
      resource savings for patients and the environment. Discussion This is the first
      such study in the UK. It shows similar results to a study in the USA. We discuss
      the study limitations, including the issue of patient recall, nature of the
      practices studied and nature of early adopter patients. Strengths include
      combining national data, practice data and local reflection. We are confident
      that the savings observed are the result of RA rather than other factors. We
      suggest that RA can be part of continuous practice improvement, given its
      benefits and the support it offers for patient confidence, self-care and shared
      decision-making. 

PMID- 25949706
TI  - Mental capacity improved by blood sugar control.

PMID- 25949707
TI  - Public health prose.

PMID- 25949708
TI  - LS Lowry, the condition of the working class and the birth of the NHS.

PMID- 25949709
TI  - Improving access to primary mental health services: are link workers the answer?
AB  - Background The incidences of common mental disorders such as anxiety, depression
      and low-level post-traumatic stress are associated with deprivation. Since 2007,
      the Improving Access to Psychological Therapy (IAPT) programme in Ealing has made
      it easier for primary care practitioners to refer patients with common mental
      disorders for treatment. However, fewer patients of a black and minority ethnic
      (BME) background were referred than expected. Setting Southall, Ealing, is a
      diverse ethnic community; over 70% of the population is classified as having a
      BME background. Aim To evaluate the effect of locating mental health link workers
      in general practitioners' (GP) surgeries on referral of BME patients to IAPT
      services. Methods In 2009, an initiative in Southall helped practitioners and
      managers that served geographic areas to work with many different agencies to
      improve whole systems of care. One strand of this work led to mental health link
      workers being placed in 6 of the 23 GP practices. They provided psychological
      therapy and raised awareness of common mental disorders in BME groups and what
      mental health services can do to improve these. Referrals to the service were
      monitored and assessed using statistical process control. Results The mean
      referral rate of BME patients for GP practices without a link worker was 0.35 per
      week per 10 000 patients and was unchanged throughout the period of the study.
      The referral rates for the six practices with a link worker increased from 0.65
      to 1.37 referrals per week per 10 000 patients. Conclusions Link workers located
      in GP practices, as part of a collaborative network of healthcare, show promise
      as one way to improve the care of patients with anxiety and depression from BME
      communities. 

PMID- 25949710
TI  - Improving patient and project outcomes using interorganisational innovation,
      collaboration and co-design.
AB  - Background Common mental disorders (CMDs) are a leading cause of disability. The
      Department of Health has launched a large-scale initiative to improve access to
      evidence-based psychological treatments, such as cognitive behavioural therapy
      (CBT), through the Improving Access to Psychological Therapy (IAPT) programme.
      Access to IAPT services by black and minority ethnic (BME) communities is lower
      than for other groups. Setting The London Borough of Ealing in west London; a
      diverse borough with areas of high BME population and relatively high
      deprivation. Aim To compare the outcomes of two linked quality improvement (QI)
      projects undertaken by Ealing Mental Health and Wellbeing Service (MHWBS), both
      with the same aim of increasing access to talking therapies for BME communities.
      Methods Application of QI methodologies supported by the NIHR CLAHRC for
      northwest London in two different settings in Ealing. One, the 'Southall
      project', was set within a wider initiative for collaborative improvements and
      shared learning (the Southall Initiative for Integrated Care) in an ethnically
      diverse area of Ealing; it was undertaken between April 2010 and September 2011.
      The second, 'the Ealing project', operated in the two other Ealing localities
      that did not have the advantage of a broader initiative for collaborative
      improvements; it was undertaken between April 2011 and September 2012. Results
      Comparison of the monthly referral rates of BME patients (standardised per 10 000
      general practitioner (GP)-registered patients) show that the Southall project was
      more effective in increasing referrals from BME communities than the Ealing
      project. Conclusion Broad local participation and ownership in the project design
      of the Southall project may explain why it was more effective in achieving its
      aims than the Ealing project which lacked these ownership-creating mechanisms. 

PMID- 25949711
TI  - Infrastructure to support modern primary care: the NAPCRG debate update.

PMID- 25949712
TI  - Public health prose.

PMID- 25949713
TI  - Leonardo da Vinci: changing approaches to teaching and learning.

PMID- 25949714
TI  - Mind the gap! Conflict and cohesion in primary care delivery models.
AB  - KEY MESSAGES: We need to learn from historic changes in accident and emergency
      (A&E) and urgent care services and identify the conflicts in provision of planned
      and unplanned care. We have choices as to whom, and how, primary care services
      are provided in the future. But we will get this wrong if we fail to recognise
      that the interface between planned and unplanned care needs to be carefully
      managed. If managed well, we might encounter the opportunity to develop high
      quality, coordinated and integrated care. WHY THIS MATTERS TO ME: I have watched
      myself and others struggle with the conflict between planned and reactive care,
      and thought it time to 'name the devil' in order to understand it and think about
      the choices ahead. Personally, I enjoy being able to deliver both planned and
      unplanned care to a practice population and would not want to lose either.

PMID- 25949715
TI  - People matter: tomorrow's workforce for tomorrow's world.
AB  - The focus of any health service, now and into the future, should be people
      delivering safe, quality care to people; care that covers not just diagnosis and
      treatment, but the whole experience that patients and their carers have of the
      service. Workforce development, the process by which the current and future
      workforce is planned and trained, must be related to current and future patterns
      of service delivery and take account of financial reality. It cannot exist in
      isolation. Despite employing 1.3 million people, upon whom up to 70% of its
      budget is spent, the NHS has been curiously relaxed about the workforce
      development of both its staff in training and of those trained staff who, with
      the impact of demographic change and the increasing speed of technological
      progress, will need to adapt to new ways of working and learn new skills. Given
      that the NHS has been repeatedly criticised by the Health Select Committee for
      its failure to link workforce planning and development with service and financial
      planning, and that inadequate staffing has been a feature of a number of recent
      organizational failures, how is this to be achieved? Some NHS organisations have
      been shown to be poor employers with a culture of bullying and fear and the use
      of suspensions and financial settlements bound to gagging clauses to remove
      whistleblowers. Gender and ethnic discrimination is an issue not yet fully
      resolved. Furthermore with the demographic changes around the increasing needs of
      an elderly population, the introduction of new technology and the increasing
      interdependency of health and social care, there is a need for a clear vision as
      to how the future NHS will be structured and developed. Fewer large specialist
      centres are likely, combined with local, community oriented integrated services
      with appropriate specialist support. Decisions need to be taken about this in
      time to give workforce development processes time to plan the best skill mix
      combinations and to develop clinicians and managers who can orchestrate NHS
      activities on a whole system basis rather than in the exclusively specialised
      silos we see today. 

PMID- 25949716
TI  - Achieving community oriented integrated care through the 2014 England GP
      contract.
AB  - WHY THIS MATTERS TO ME: I have been involved in developing different forms of
      community-oriented integrated care since 1989 when I set up the Liverpool Primary
      Care Facilitation Project. I never cease to be amazed at how effective and
      enjoyable it is when primary care practitioners and managers can work together
      across organisational boundaries to improve healthcare for local populations. I
      also never cease to be surprised at how hard it seems to be for many to believe
      that such an approach could be even contemplated, let alone systematically
      taught, applied and evaluated. In West London, I have seen the valuable effect of
      the Integrated Care Pilot at providing one of the key ingredients of community
      oriented integrated care - geographic clustering of general practices (termed
      Health Networks) that provide a regular space where people of different
      disciplines can come together to learn from and with each other, and co-create
      things that improve the health of local people. I believe that the April 2014
      changes to the England GP contract provide an opportunity for these Health
      Networks to make a quantum leap in achieving community-oriented integrated care
      and with it a renaissance of the NHS.

PMID- 25949717
TI  - Impact of a care plan: diabetes case study.

PMID- 25949719
TI  - Facing the modern and the medical.

PMID- 25949718
TI  - Public health prose.

PMID- 25949720
TI  - Mandated Local Health Networks across the province of Quebec: a better
      collaboration with primary care working in the communities?
AB  - Background In 2004, the Quebec government implemented an important reform of the
      healthcare system. The reform was based on the creation of new organisations
      called Health Services and Social Centres (HSSC), which were formed by merging
      several healthcare organisations. Upon their creation, each HSSC received the
      legal mandate to establish and lead a Local Health Network (LHN) with different
      partners within their territory. This mandate promotes a 'population-based
      approach' based to the responsibility for the population of a local territory.
      Objective The aim of this paper is to illustrate and discuss how primary
      healthcare organisations (PHC) are involved in mandated LHNs in Quebec. For
      illustration, we describe four examples that facilitate a better understanding of
      these integrated relationships. Results The development of the LHNs and the
      different collaboration relationships are described through four examples: (1)
      improving PHC services within the LHN - an example of new PHC models; (2)
      improving access to specialists and diagnostic tests for family physicians
      working in the community - an example of centralised access to specialists
      services; (3) improving chronic-disease-related services for the population of
      the LHN - an example of a Diabetes Centre; and (4) improving access to family
      physicians for the population of the LHN - an example of the centralised waiting
      list for unattached patients. Conclusion From these examples, we can see that the
      implementation of large-scale reform involves incorporating actors at all levels
      in the system, and facilitates collaboration between healthcare organisations,
      family physicians and the community. These examples suggest that the reform
      provided room for multiple innovations. The planning and organisation of health
      services became more focused on the population of a local territory. The LHN
      allows a territorial vision of these planning and organisational processes to
      develop. LHN also seems a valuable lever when all the stakeholders are involved
      and when the different organisations serve the community by providing acute care
      and chronic care, while taking into account the social, medical and nursing
      fields. 

PMID- 25949721
TI  - Patient demographics as a predictive tool of consultation duration.
AB  - This paper reports on a study undertaken to test the hypothesis that known
      patient demographics will be a reasonably reliable predictor of the duration of a
      patient's consultation with a general practitioner, regardless of the medical
      experience of an individual physician. 

PMID- 25949723
TI  - Public health prose.

PMID- 25949722
TI  - The prevalence of comorbidities among people living with HIV in Brent: a diverse
      London Borough.
AB  - Background HIV has changed from a rapidly deteriorating illness to a complex
      chronic disease, with increasing incidences of comorbidity, including cancer, and
      liver, lung and cardiovascular diseases. North West London has 6719 individuals
      living with the human immunodeficiency virus (HIV), 873 of whom reside in the
      London Borough of Brent. Traditionally, commissioning services have focused on
      HIV therapy alone without considering how comorbidity affects treatment outcome
      and total service costs. Setting The setting for the study was NHS Brent Primary
      Care Trust, London UK. Question What associated comorbidities are present in
      people in Brent (London, UK) living with HIV, and how common are they? Methods A
      point-prevalence audit of retrospective data was conducted on all HIV-positive
      patients in Brent (financial year 2011/12). Data were collected from genito
      urinary medicine (GUM) services, community services and general practitioners
      (GPs) on HIV diagnosis, patient demographics and past/current comorbidities:
      hepatitis B and C, cardiovascular disease, diabetes and mental health disorders.
      Results This study identified that 29% of people living with HIV/AIDS (PLWHA) in
      Brent have at least one comorbidity. The most common was hepatitis, followed by
      mental health disorders and cardiovascular disease (CVD). Comorbidity was more
      likely in older male patients (in particular CVD and diabetes) and White patients
      (except for diabetes which was more common in Asian groups).
      Discussion/Conclusion Many PLWHA in Brent suffer from a number of other
      conditions, which appear largely independent of HIV. Findings confirm the need to
      treat HIV as a long-term condition, including patient education, empowerment and
      encouraging self-management. The multi-morbidity of many PLWHA suggests a role
      for both primary care and collaborative, holistic, patient-centred and
      individualised healthcare. Service providers and commissioners need to consider
      comorbidities in their treatment of and provision of services for PLWHA. This
      study also highlighted the need for services to address limitations of their data
      collection systems. 

PMID- 25949724
TI  - 'Painting with scissors': Matisse and creativity in illness.

PMID- 25949725
TI  - What is evidence?

PMID- 25949726
TI  - Evidence-based practice: reflections from five European case studies.
AB  - Background Evidence-based practice (EBP) is now the accepted orthodoxy in
      clinical practice and developed from evidence-based medicine. EBP is based on a
      specific type of evidence that is derived from studies based on randomised
      controlled trials (RCT). This type of evidence is suited to acute medical care
      and is more problematic for other clinicians such as nurses and therapists,
      particularly when they are situated within community or primary care settings.
      Setting Five stroke care services in England (2), Sweden (2) and Poland (1). Aims
      To reflect on the evidence gained from these case studies to shed light on
      various aspects of EBP. This paper focuses on three key issues: (1) the
      importance of context for evidence, (2) the nature of knowledge, and (3)
      professional hierarchies. Methods Five qualitative case studies into stroke care
      were carried out in England, Sweden and Poland. One hundred and twenty semi
      structured interviews were carried out with a range of healthcare staff who
      provided specialised and non-specialised stroke care in acute, community and
      primary care between October 2010 and September 2011. Medical doctors, nurses and
      different therapists were included in the samples in all five case studies. For
      this paper, we reflect on some aspects of this work to illuminate the different
      interprofessional perspectives relating to EBP in stroke care. Results The lack
      of RCT-based evidence in the community and primary care sectors can lead to the
      clinicians working in these sectors being perceived as having a lower status.
      Clinicians use both tacit and encoded knowledge to guide their practice and there
      existed both intraand interprofessional tensions in these two types of knowledge.
      The professional hierarchy of stroke teams varies with national context and the
      role of the non-specialists is less valued in stroke care. 

PMID- 25949727
TI  - Understanding context in healthcare research and development.
AB  - This is a review of a paper by Bayliss et al in the Annals of Family Medicine
      that argues that traditional research methods 'are not well suited to addressing
      multi-faceted problems, such as understanding the complex interaction of multi
      morbid chronic illness with social, environmental and healthcare systems'.
      Bayliss et al conclude that research that can be relied on requires methods that
      are 'participatory, mixed methods, multi-level, and engage communities'. 

PMID- 25949728
TI  - Lionel Shriver at the Tate: a conversation.

PMID- 25949729
TI  - Carousel of servitude.

PMID- 25949730
TI  - A compelling story for change.

PMID- 25949731
TI  - The Professor Lord Darzi interview.

PMID- 25949732
TI  - Medical students' attitudes towards general practice and factors affecting career
      choice: a questionnaire study.
AB  - Background The current issue of general practice recruitment is a significant
      challenge and concern. In order to address this, it is vital to understand
      medical students' attitudes towards general practice and what influences their
      choice of intended career. Method We used a questionnaire study to examine these
      attitudes across all years at Imperial College Medical School and to understand
      what a group of London medical students' current intended career choices were.
      Results We found that only 13% of students ranked general practice as their first
      choice career despite having a generally realistic and positive attitude towards
      the speciality. They highlighted that the main influence on future career choice
      was interest in the specific speciality and that lifestyle factors did not seem
      to be so important. Conclusion Exposure to general practice, primary care
      research and student GP societies might play some part in increasing interest,
      but more work is needed to understand why students are rejecting general practice
      and what we can do collectively to attract students into choosing a career in
      primary care. 

PMID- 25949733
TI  - Translating the medical home into patient-centred language.
AB  - Background The patient-centred medical home (PCMH) is a healthcare delivery model
      that aims to make health care more effective and affordable and to curb the rise
      in episodic care resulting from increasing costs and sub-specialisation of health
      care. Although the PCMH model has been implemented in many different healthcare
      settings, little is known about the PCMH in rural or underserved settings.
      Further, less is known about patients' understanding of the PCMH and its effect
      on their care. Aims The goal of this project was to ascertain the patient
      perspective of the PCMH and develop meaningful language around the PCMH to help
      inform and promote patients' participation with the PCMH. Method The High Plains
      Research Network Community Advisory Council (CAC) is comprised of a diverse group
      of individuals from rural eastern Colorado. The CAC and its academic partners
      started this project by receiving a comprehensive education on the PCMH. Using a
      community-based participatory research approach, the CAC translated technical
      medical jargon on the PCMH into a core message that the 'Medical Home is
      Relationship'. Results The PCMH should focus on the relationship of the patient
      with their personal physician. Medical home activities should be used to support
      and strengthen this relationship. Conclusion The findings serve as a reminder of
      the crucial elements of the PCMH that make it truly patient centred and the
      importance of engaging local patients in developing and implementing the medical
      home. 

PMID- 25949734
TI  - Evaluating the care of patients with long term conditions.
AB  - Approaches to evaluating the care of patients with long-term conditions first
      need to be framed around defining outcomes that 'matter to people', rather than
      those that are focused on disease and easily measurable. Secondly, approaches to
      evaluating such care should be organised with the ability to 'deliver what
      matters to people' - such models of care must allow for the opportunity to
      maximise the impact of primary care. Finally, any approach to evaluation must
      also 'enable the delivery of what matters to people', including approaches to
      promote self-care, well-being and interprofessional workforce development
      organised around educational networks. 

PMID- 25949735
TI  - How do rural patients benefit from the patient-centred medical home? A card study
      in the High Plains Research Network.
AB  - Context The patient-centred medical home (PCMH) has become a dominant model for
      improving the quality and cost of primary care. Geographic isolation, small
      populations, privacy concerns and staffing requirements may limit implementation
      of the PCMH in clinical practice. Objective To determine the primary care
      provider perceived benefit of PCMH for patients in rural Colorado. Design,
      setting and participants The High Plains Research Network (HPRN) is a community
      and practice-based research network spanning 30 000 square miles in 16 counties
      in eastern Colorado. The HPRN consists of 58 practices, 120 primary care
      clinicians and 145 000 residents. Main outcome measures Providers' perceived
      benefit of PCMH for individual patients. Results Seventy-eight providers in 37
      practices saw 1093 patients and completed 1016 surveys. There was wide variation
      among the provider-perceived benefits of PCMH elements ranging from 9% for group
      visits to 64% for electronic prescribing. Provider-perceived benefit was higher
      for patients with a chronic medical condition. Conclusions Rural primary care
      providers perceived patient benefit for numerous elements of the PCMH. There is
      need to consider what PCMH elements may be required in practice and what
      components might be optional. Our findings reveal that rural practices share PCMH
      aspirations including commitment to quality, safety, outcomes, cost reduction,
      and patient and provider satisfaction. These findings support the need for
      ongoing conversation about how to best provide a locally relevant medical home. 

PMID- 25949736
TI  - Meeting the needs of vulnerable patients: The need for team working across
      general practice and community nursing services.
AB  - General practitioners and district nurses have a long history of providing care
      outside the hospital setting. With health care increasingly moving out of the
      hospital setting, there are more opportunities for general practitioners and
      district nurses to work together to meet the health needs of the local
      population. However, the reduction in qualified specialist practitioner district
      nurses over the last decade is concerning. The need for an effective district
      nursing service has been recognised by the Department of Health in their own
      model - the nature of district nursing work, often over a long period, enables
      relationships to develop with the patient, family and informal carers as a basis
      for anticipatory care to manage long-term conditions. Communication and
      understanding of the role are central to enhance effective working between
      general practitioners and district nurses, which can be fostered by engagement in
      community-oriented integrated care and case management. 

PMID- 25949737
TI  - Community development through health gain and service change - do it now!
AB  - This article explores the principles and practice of community development (CD)
      in health from a primary care perspective. CD is defined and examples are given.
      There are many misconceptions about the term and so we explain what CD is not:
      for instance, it is not social prescribing, nor is it conventional public health
      interventions. The benefits for practices, general practitioners and clinical
      commissioning groups are outlined, and the current evidence on cost-benefit is
      given. In essence, the benefits are health gain and effective community-driven
      service change. Risks, side effects and complications are described. Finally, the
      Charter for Community Development in Health is a call to action for clinical
      commissioning groups and policy-makers. We have an approach that changes people's
      lives for the better - let's harness it! 

PMID- 25949738
TI  - Community-oriented integrated mental health services.
AB  - Unprecedented levels of cost containment in NHS and social care organisations -
      together with integration as a policy priority - make this a key moment for fresh
      ways of thinking about how to commission and provide community-based integrated
      services that meet the challenge of local accountability and citizen
      participation. This is nowhere more important than in mental health. Primary care
      with its local orientation is properly at the heart of this agenda, but there is
      a need for new forms of leadership for collaboration in the sector. In this
      context, the contribution of general practitioner (GP) networks is likely to be
      fundamental. This paper is a brief discussion of some of the issues associated
      with GP networks and mental health, set in the context of a round table
      discussion with three sets of participants at a 2014 London Journal of Primary
      Care/Royal College of General Practitioners conference. The conference provided a
      forum for capturing a diversity of experience and knowledge and for turning this
      into a force for critical transformation. This paper describes a contribution to
      the day. 

PMID- 25949740
TI  - How do we make community-oriented integrated care work?

PMID- 25949741
TI  - Commentary on text of interview with Professor Lord Ara Darzi: 'Desirable? Yes;
      but is it achievable?'.
AB  - This personal commentary explores some issues that arise in the text of the
      interview with Lord Darzi published in LJPC 6.6, from a point of view of an
      interest in health policy and change in healthcare organisations. It suggests
      that the vision is desirable but that there are four major questions about ready
      implementation that the field needs to consider: 1 Can primary care development
      and investment be protected in a cold financial climate? 2 Does the current
      marketisation of health care erode integration? 3 Does the health and social care
      system in London behave like a real system? 4 Is there really a cultural shift
      towards empowerment and organisational learning? 

PMID- 25949739
TI  - 4th annual primary care ethics conference: ethics education and lifelong
      learning.
AB  - Primary care ethics is a field of study that has recently found new life, with
      calls to establish the relevance of ethical discussion in general practice, to
      gather a body of literature and to carve out an intellectual space for primary
      care on the academic landscape of bioethics. In this report, we reflect on the
      key strands of the 4th primary care ethics conference held at the Royal Society
      of Medicine, on a theme of ethics education and lifelong learning: first, to
      produce insights that have relevance for policy and practice; and second, to
      illustrate the idea that not only is ethics relevant in primary care, but primary
      care is relevant in medical ethics. Core themes included the advantages and
      disadvantages of prescriptive ways of doing ethics in education, ethical
      reflection and potential risk to professional status, the need to deal with
      societal change and to take on board the insights gained from empirical work,
      whether this is about different kinds of fatherhood, or work on the causes of
      moral distress in healthcare workers. 

PMID- 25949742
TI  - My life, my way, with your support: George's story.
AB  - KEY MESSAGES: The importance of early discussion and planning for end of life.The
      need to take risks that are considered and thought through, but nevertheless
      risks that will enhance end of life experience. RELATED LJPC PAPERS: Millington
      Sanders C, Nadicksbernd JJ, O'Sullivan C, Morgan T, Raleigh A, Yeun P and Ormerod
      G (2013) Electronic palliative care co-ordination system: an electronic record
      that supports communication for end-of-life care - a pilot in Richmond, UK.
      London Journal of Primary Care 5: 106-110.
      http://www.radcliffehealth.com/ljpc/article/electronic-palliative-care-co
      ordination-system-electronic-record-supports Thomas K (2009) Improving end of
      life care: a matter of life and death. London Journal of Primary Care 2: 89-92.
      http://www.radcliffehealth.com/sites/radcliffehealth.com/files/ljpc_articles/2_2_
      .pdf. WHY THIS MATTERS TO ME: I am passionate about empowering people to have a
      choice and exert control over their lives, especially about how they spend their
      last weeks, days and hours of life. I want to ask the difficult questions of
      professionals and challenge what is perceived as the norm in practice, doing so
      by making sure that they listen to the voice of the person that they serve, hear
      it and act upon it.

PMID- 25949743
TI  - Non-alcoholic liver disease in an HGV driver.

PMID- 25949744
TI  - Multiple conformational states in retrospective virtual screening - homology
      models vs. crystal structures: beta-2 adrenergic receptor case study.
AB  - BACKGROUND: Distinguishing active from inactive compounds is one of the crucial
      problems of molecular docking, especially in the context of virtual screening
      experiments. The randomization of poses and the natural flexibility of the
      protein make this discrimination even harder. Some of the recent approaches to
      post-docking analysis use an ensemble of receptor models to mimic this naturally
      occurring conformational diversity. However, the optimal number of receptor
      conformations is yet to be determined. In this study, we compare the results of a
      retrospective screening of beta-2 adrenergic receptor ligands performed on both
      the ensemble of receptor conformations extracted from ten available crystal
      structures and an equal number of homology models. Additional analysis was also
      performed for homology models with up to 20 receptor conformations considered.
      RESULTS: The docking results were encoded into the Structural Interaction
      Fingerprints and were automatically analyzed by support vector machine. The use
      of homology models in such virtual screening application was proved to be
      superior in comparison to crystal structures. Additionally, increasing the number
      of receptor conformational states led to enhanced effectiveness of active vs.
      inactive compounds discrimination. CONCLUSIONS: For virtual screening purposes,
      the use of homology models was found to be most beneficial, even in the presence
      of crystallographic data regarding the conformational space of the receptor. The
      results also showed that increasing the number of receptors considered improves
      the effectiveness of identifying active compounds by machine learning methods.
      Graphical abstractComparison of machine learning results obtained for various
      number of beta-2 AR homology models and crystal structures.

PMID- 25949745
TI  - Analytical Side-to-Side Related Anastomotic Strategies and Artery Patching.
AB  - Suture line stress concentration and intimal hyperplasia are related to the long
      term complications of end-toside and side-to-side anastomosis. Several factors,
      such as hemodynamic effects, biological activities and the mechanical properties
      of the blood vessels, are identified to influence the problem. Yet, it is not
      completely clear which are the factors that influence most the long-term
      complications and in what specific way. This study aims to examine if elastic
      (compliance) mismatch increases the stress concentration and intimal thickening
      at the suture line. Better compliance may be obtained by using grafts with
      similar mechanical properties to the host artery or by anastomosis techniques
      that utilize vein patches and cuffs (Taylor-patch and Miller-cuff anastomosis).
      The anastomosis model used in this study is a circular cylindrical system
      consisting of two semi-cylinders, interconnected by two hinges. The internal
      blood pressure is applied on the arterial walls. The static and dynamic responses
      are analytically derived in terms of radial and tangential displacements,
      internal forces and strains of the two blood vessels and rotation of their cross
      section. Results suggest that increased elastic mismatch between the artery and
      the graft may promote elevated intimal thickening due to large incompatible
      angles at the junction, whereas there is no correlation between elastic mismatch
      and elevated stress concentration at the suture line. Another interesting
      application of the present model is the patching of arteries as applied in
      carotid endarterectomy. 

PMID- 25949746
TI  - Two-stage revision total knee arthroplasty in cases of periprosthetic joint
      infection: an analysis of 50 cases.
AB  - OBJECTIVES: A periprosthetic joint infection (PJI) is a significant complication
      after total knee arthroplasty (TKA). Still there is no agreement on a perfect
      diagnosis and treatment algorithm. The aim of this study was to evaluate the
      success and revision rates after two-stage revision total knee arthroplasty (TKA)
      and factors that affect the success rate. MATERIAL AND METHODS: 50 consecutive
      two-stage revision TKAs were performed between January 2011 and December 2012. We
      retrospectively reviewed study patient's charts including demographics, prior
      surgeries, comorbidities, incidence of persistent infection and revisions. At the
      final follow-up examination the patient's satisfaction, pain level and disorders
      were evaluated. A successful clinical outcome was defined as a functioning
      prosthesis without wound healing disorders, no sinuses tracts or other clinical
      evidence of a persistent infection. Results : Re-implantation of prosthesis was
      performed in 47 cases; three patients received a septic arthrodesis. Twelve
      patients had a persistent infection despite two-stage re-implantation resulting
      in a success rate of 76.0%. In eight of these twelve patients an infecting germ
      was isolated during second-stage procedure. Three patients received another two
      stage revision arthroplasty and one patient an above knee amputation. A revision
      was performed in 23 of 50 patients (46.0%). Factors that diminish the success
      rate were further operations after primary TKA (p = 0.048), prior revision
      arthroplasties after TKA (p = 0.045), nicotine abuse (p = 0.048), Charlson
      comorbidity index above a score of 2 (p = 0.031) and a mixed flora during first
      stage procedure (p < 0.001). Age, sex, immune status, chronic anticoagulant use,
      rheumatoid arthritis, body mass index and the presence of multidrug resistant
      germs showed no significant effect on success rate (p > 0.05). Conclusion : We
      found that patients who required surgery after the primary TKA, had a higher
      Charlson comorbidity index or were found to have mixed flora during explantation.
      The treatment of PJI remains difficult, both for the patient and for the treating
      surgeons.

PMID- 25949747
TI  - A Comparison of Somatic Variables of Elite Ice Hockey Players from the Czech ELH
      and Russian KHL.
AB  - The goals of this study were to evaluate the basic morphological variables of
      contemporary elite ice hockey players, compare the parameters of players in the
      top Russian ice hockey league (KHL) with those of the top Czech ice hockey league
      (ELH), and to evaluate the parameters of players according to their position in
      the game. The research participants included 30 KHL players (mean age: 27.1 +/-
      5.1 years) and 25 ELH players (mean age: 26.4 +/- 5.8 years). We determined body
      height, body mass, and body composition (body fat, fat-free mass, segmental fat
      analysis). All measurements were performed at the end of preseason training. The
      KHL players had the following anthropometric characteristics: body height 182.97
      +/- 5.61 cm (forward) and 185.72 +/- 3.57 cm (defenseman), body mass 89.70 +/-
      5.28 kg (forward) and 92.52 +/- 4.01 kg (defenseman), body fat 10.76 +/- 0.63 kg
      (forward) and 11.10 +/- 0.48 kg (defenseman), fat-free mass 78.94 +/- 4.65 kg
      (forward) and 81.42 +/- 3.52 kg (defenseman). The values for ELH players were as
      follows: body height 182.06 +/- 5.93 cm (forward) and 185.88 +/- 7.13 cm
      (defenseman), body mass 88.47 +/- 7.06 kg (forward) and 89.36 +/- 10.91 kg
      (defenseman), body fat 12.57 +/- 2.89 kg (forward) and 11.91 +/- 3.10 kg
      (defenseman), fat-free mass 75.93 +/- 6.54 kg (forward) and 77.46 +/- 7.89 kg
      (defenseman). The results indicate that it is beneficial to ice hockey players to
      have increased body mass and lower body fat, which leads to higher muscle mass,
      thus enabling a player to perform at the highest level and meet the specific
      challenges of the game. 

PMID- 25949748
TI  - From the Editor-in-Chief: Make Some Time to Share Your Creative Ideas and Best
      Practices!

PMID- 25949749
TI  - Letter to the editor.

PMID- 25949750
TI  - Letter to the editor.

PMID- 25949751
TI  - Prop demonstrations in biology lectures facilitate student learning and
      performance.
AB  - Science students can benefit from visual aids. In biology lectures, visual aids
      are usually limited to tables, figures, and PowerPoint presentations. In this IRB
      approved study, we examined the effectiveness of the use of five prop
      demonstrations, three of which are at the intersection of biology and chemistry,
      in three community college biology courses. We hypothesized that students'
      performance on test questions is enhanced by the use of prop demonstrations.
      Consistent with our hypothesis, we showed that students learn more effectively
      and perform better on questions that relate to demonstrations than on questions
      related to lessons that do not have a demonstration component. 

PMID- 25949752
TI  - When Do Students "Learn-to-Comprehend" Scientific Sources?: Evaluation of a
      Critical Skill in Undergraduates Progressing through a Science Major.
AB  - In response to the publication of Vision and Change, the biology department at
      Elmhurst College revised our curriculum to better prepare students for a career
      in science with the addition of various writing assignments in every course. One
      commonality among all of the assignments is the ability to comprehend and
      critically evaluate scientific literature to determine relevancy and possible
      future research. Several previous reports have analyzed specific methodologies to
      improve student comprehension of scientific writing and critical thinking skills,
      yet none of these examined student growth over an undergraduate career. In this
      study, we hypothesized upper-level students would be better able to comprehend
      and critically analyze scientific literature than introductory biology majors.
      Biology students enrolled in an introductory (200-level), mid- (300-level), or
      late-career (400-level) course were tasked with reading and responding to
      questions regarding a common scientific article and rating their comfort and
      confidence in reading published literature. As predicted, upper-level (mid- and
      late-career) students showed increases in comprehension and critical analysis
      relative to their first-year peers. Interestingly, we observed that upper-level
      students read articles differently than introductory students, leading to
      significant gains in understanding and confidence. However, the observed gains
      were modest overall, indicating that further pedagogical change is necessary to
      improve student skills and confidence in reading scientific articles while
      fulfilling the Vision and Change recommendations. 

PMID- 25949753
TI  - Case study teaching method improves student performance and perceptions of
      learning gains.
AB  - Following years of widespread use in business and medical education, the case
      study teaching method is becoming an increasingly common teaching strategy in
      science education. However, the current body of research provides limited
      evidence that the use of published case studies effectively promotes the
      fulfillment of specific learning objectives integral to many biology courses.
      This study tested the hypothesis that case studies are more effective than
      classroom discussions and textbook reading at promoting learning of key
      biological concepts, development of written and oral communication skills, and
      comprehension of the relevance of biological concepts to everyday life. This
      study also tested the hypothesis that case studies produced by the instructor of
      a course are more effective at promoting learning than those produced by
      unaffiliated instructors. Additionally, performance on quantitative learning
      assessments and student perceptions of learning gains were analyzed to determine
      whether reported perceptions of learning gains accurately reflect academic
      performance. The results reported here suggest that case studies, regardless of
      the source, are significantly more effective than other methods of content
      delivery at increasing performance on examination questions related to chemical
      bonds, osmosis and diffusion, mitosis and meiosis, and DNA structure and
      replication. This finding was positively correlated to increased student
      perceptions of learning gains associated with oral and written communication
      skills and the ability to recognize connections between biological concepts and
      other aspects of life. Based on these findings, case studies should be considered
      as a preferred method for teaching about a variety of concepts in science
      courses. 

PMID- 25949754
TI  - Teaching information literacy skills to sophomore-level biology majors.
AB  - Many undergraduate students lack a sound understanding of information literacy.
      The skills that comprise information literacy are particularly important when
      combined with scientific writing for biology majors as they are the foundation
      skills necessary to complete upper-division biology course assignments, better
      train students for research projects, and prepare students for graduate and
      professional education. To help undergraduate biology students develop and
      practice information literacy and scientific writing skills, a series of three
      one-hour hands-on library sessions, discussions, and homework assignments were
      developed for Biological Literature, a one-credit, one-hour-per-week, required
      sophomore-level course. The embedded course librarian developed a learning
      exercise that reviewed how to conduct database and web searches, the difference
      between primary and secondary sources, source credibility, and how to access
      articles through the university's databases. Students used the skills gained in
      the library training sessions for later writing assignments including a formal
      lab report and annotated bibliography. By focusing on improving information
      literacy skills as well as providing practice in scientific writing, Biological
      Literature students are better able to meet the rigors of upper-division biology
      courses and communicate research findings in a more professional manner. 

PMID- 25949755
TI  - Exploring metagenomics in the laboratory of an introductory biology course.
AB  - Four laboratory modules were designed for introductory biology students to
      explore the field of metagenomics. Students collected microbes from environmental
      samples, extracted the DNA, and amplified 16S rRNA gene sequences using
      polymerase chain reaction (PCR). Students designed functional metagenomics
      screens to determine and compare antibiotic resistance profiles among the
      samples. Bioinformatics tools were used to generate and interpret phylogenetic
      trees and identify homologous genes. A pretest and posttest were used to assess
      learning gains, and the results indicated that these modules increased student
      performance by an average of 22%. Here we describe ways to engage students in
      metagenomics-related research and provide readers with ideas for how they can
      start developing metagenomics exercises for their own classrooms. 

PMID- 25949756
TI  - Guided inquiry and consensus-building used to construct cellular models.
AB  - Using models helps students learn from a "whole systems" perspective when
      studying the cell. This paper describes a model that employs guided inquiry and
      requires consensus building among students for its completion. The model is
      interactive, meaning that it expands upon a static model which, once completed,
      cannot be altered and additionally relates various levels of biological
      organization (molecular, organelle, and cellular) to define cell and organelle
      function and interaction. Learning goals are assessed using data summed from
      final grades and from images of the student's final cell model (plant, bacteria,
      and yeast) taken from diverse seventh grade classes. Instructional figures
      showing consensus-building pathways and seating arrangements are discussed.
      Results suggest that the model leads to a high rate of participation, facilitates
      guided inquiry, and fosters group and individual exploration by challenging
      student understanding of the living cell. 

PMID- 25949757
TI  - Do you kiss your mother with that mouth? An authentic large-scale undergraduate
      research experience in mapping the human oral microbiome.
AB  - Clinical microbiology testing is crucial for the diagnosis and treatment of
      community and hospital-acquired infections. Laboratory scientists need to utilize
      technical and problem-solving skills to select from a wide array of microbial
      identification techniques. The inquiry-driven laboratory training required to
      prepare microbiology graduates for this professional environment can be difficult
      to replicate within undergraduate curricula, especially in courses that
      accommodate large student cohorts. We aimed to improve undergraduate scientific
      training by engaging hundreds of introductory microbiology students in an
      Authentic Large-Scale Undergraduate Research Experience (ALURE). The ALURE aimed
      to characterize the microorganisms that reside in the healthy human oral cavity
      the oral microbiome-by analyzing hundreds of samples obtained from student
      volunteers within the course. Students were able to choose from selective and
      differential culture media, Gram-staining, microscopy, as well as polymerase
      chain reaction (PCR) and 16S rRNA gene sequencing techniques, in order to
      collect, analyze, and interpret novel data to determine the collective oral
      microbiome of the student cohort. Pre- and postsurvey analysis of student
      learning gains across two iterations of the course (2012-2013) revealed
      significantly higher student confidence in laboratory skills following the
      completion of the ALURE (p < 0.05 using the Mann-Whitney U-test). Learning
      objectives on effective scientific communication were also met through effective
      student performance in laboratory reports describing the research outcomes of the
      project. The integration of undergraduate research in clinical microbiology has
      the capacity to deliver authentic research experiences and improve scientific
      training for large cohorts of undergraduate students. 

PMID- 25949758
TI  - Facilitating improvements in laboratory report writing skills with less grading:
      a laboratory report peer-review process.
AB  - Incorporating peer-review steps in the laboratory report writing process provides
      benefits to students, but it also can create additional work for laboratory
      instructors. The laboratory report writing process described here allows the
      instructor to grade only one lab report for every two to four students, while
      giving the students the benefits of peer review and prompt feedback on their
      laboratory reports. Here we present the application of this process to a
      sophomore level genetics course and a freshman level cellular biology course,
      including information regarding class time spent on student preparation
      activities, instructor preparation, prerequisite student knowledge, suggested
      learning outcomes, procedure, materials, student instructions, faculty
      instructions, assessment tools, and sample data. T-tests comparing individual and
      group grading of the introductory cell biology lab reports yielded average scores
      that were not significantly different from each other (p = 0.13, n = 23 for
      individual grading, n = 6 for group grading). T-tests also demonstrated that
      average laboratory report grades of students using the peer-review process were
      not significantly different from those of students working alone (p = 0.98, n = 9
      for individual grading, n = 6 for pair grading). While the grading process
      described here does not lead to statistically significant gains (or reductions)
      in student learning, it allows student learning to be maintained while decreasing
      instructor workload. This reduction in workload could allow the instructor time
      to pursue other high-impact practices that have been shown to increase student
      learning. Finally, we suggest possible modifications to the procedure for
      application in a variety of settings. 

PMID- 25949759
TI  - Practical bioremediation course - laboratory exercises on biodegradation of
      cationic surfactant.

PMID- 25949760
TI  - Culturing life from air: using a surface air system to introduce discovery-based
      research in aerobiology into the undergraduate biology curriculum.

PMID- 25949761
TI  - The biology experimental design challenge: an interactive approach to enhance
      students' understanding of scientific inquiry in the context of an introductory
      biology course.

PMID- 25949762
TI  - The HeLa Documentary Film: An Engaging Writing and Culturally Relevant Assignment
      on Cell Division and Ethics for Nonscience Majors(?).

PMID- 25949763
TI  - Using lecture demonstrations to visualize biological concepts.

PMID- 25949764
TI  - Microbial life in a winogradsky column: from lab course to diverse research
      experience.

PMID- 25949765
TI  - Increase the visibility of microbial growth in a winogradsky column by
      substituting diatomaceous Earth for sediment.

PMID- 25949766
TI  - Use of Constructed-Response Questions to Support Learning of Cell Biology during
      Lectures.

PMID- 25949767
TI  - Comparing outdated and updated textbook figures helps introduce undergraduates to
      primary literature.

PMID- 25949769
TI  - The ASM Curriculum Guidelines for Undergraduate Microbiology: A Case Study of the
      Advocacy Role of Societies in Reform Efforts.
AB  - A number of national reports, including Vision and Change in Undergraduate
      Biology Education: A Call to Action, have called for drastic changes in how
      undergraduate biology is taught. To that end, the American Society for
      Microbiology (ASM) has developed new Curriculum Guidelines for undergraduate
      microbiology that outline a comprehensive curriculum for any undergraduate
      introductory microbiology course or program of study. Designed to foster enduring
      understanding of core microbiology concepts, the Guidelines work synergistically
      with backwards course design to focus teaching on student-centered goals and
      priorities. In order to qualitatively assess how the ASM Curriculum Guidelines
      are used by educators and learn more about the needs of microbiology educators,
      the ASM Education Board distributed two surveys to the ASM education community.
      In this report, we discuss the results of these surveys (353 responses). We found
      that the ASM Curriculum Guidelines are being implemented in many different types
      of courses at all undergraduate levels. Educators indicated that the ASM
      Curriculum Guidelines were very helpful when planning courses and assessments. We
      discuss some specific ways in which the ASM Curriculum Guidelines have been used
      in undergraduate classrooms. The survey identified some barriers that
      microbiology educators faced when trying to adopt the ASM Curriculum Guidelines,
      including lack of time, lack of financial resources, and lack of supporting
      resources. Given the self-reported challenges to implementing the ASM Curriculum
      Guidelines in undergraduate classrooms, we identify here some activities related
      to the ASM Curriculum Guidelines that the ASM Education Board has initiated to
      assist educators in the implementation process. 

PMID- 25949770
TI  - Regulation of System xc(-) by Pharmacological Manipulation of Cellular Thiols.
AB  - The cystine/glutamate exchanger (system xc (-)) mediates the transport of cystine
      into the cell in exchange for glutamate. By releasing glutamate, system xc (-)
      can potentially cause excitotoxicity. However, through providing cystine to the
      cell, it regulates the levels of cellular glutathione (GSH), the main endogenous
      intracellular antioxidant, and may protect cells against oxidative stress. We
      tested two different compounds that deplete primary cortical cultures containing
      both neurons and astrocytes of intracellular GSH, L-buthionine-sulfoximine (L
      BSO), and diethyl maleate (DEM). Both compounds caused significant concentration
      and time dependent decreases in intracellular GSH levels. However; DEM caused an
      increase in radiolabeled cystine uptake through system xc (-), while unexpectedly
      BSO caused a decrease in uptake. The compounds caused similar low levels of
      neurotoxicity, while only BSO caused an increase in oxidative stress. The
      mechanism of GSH depletion by these two compounds is different, DEM directly
      conjugates to GSH, while BSO inhibits gamma-glutamylcysteine synthetase, a key
      enzyme in GSH synthesis. As would be expected from these mechanisms of action,
      DEM caused a decrease in intracellular cysteine, while BSO increased cysteine
      levels. The results suggest that negative feedback by intracellular cysteine is
      an important regulator of system xc (-) in this culture system. 

PMID- 25949773
TI  - Size-Dependent Photon Emission from Organometal Halide Perovskite Nanocrystals
      Embedded in an Organic Matrix.
AB  - In recent years, organometal halide perovskite materials have attracted
      significant research interest in the field of optoelectronics. Here, we introduce
      a simple and low-temperature route for the formation of self-assembled perovskite
      nanocrystals in a solid organic matrix. We demonstrate that the size and
      photoluminescence peak of the perovskite nanocrystals can be tuned by varying the
      concentration of perovskite in the matrix material. The physical origin of the
      blue shift of the perovskite nanocrystals' emission compared to its bulk phase is
      also discussed.

PMID- 25949771
TI  - The protective effect of lipoic acid on selected cardiovascular diseases caused
      by age-related oxidative stress.
AB  - Oxidative stress is considered to be the primary cause of many cardiovascular
      diseases, including endothelial dysfunction in atherosclerosis and ischemic heart
      disease, hypertension, and heart failure. Oxidative stress increases during the
      aging process, resulting in either increased reactive oxygen species (ROS)
      production or decreased antioxidant defense. The increase in the incidence of
      cardiovascular disease is directly related to age. Aging is also associated with
      oxidative stress, which in turn leads to accelerated cellular senescence and
      organ dysfunction. Antioxidants may help lower the incidence of some pathologies
      of cardiovascular diseases and have antiaging properties. Lipoic acid (LA) is a
      natural antioxidant which is believed to have a beneficial effect on oxidative
      stress parameters in relation to diseases of the cardiovascular system. 

PMID- 25949772
TI  - Protective Role of Nuclear Factor E2-Related Factor 2 against Acute Oxidative
      Stress-Induced Pancreatic beta -Cell Damage.
AB  - Oxidative stress is implicated in the pathogenesis of pancreatic beta-cell
      dysfunction that occurs in both type 1 and type 2 diabetes. Nuclear factor E2
      related factor 2 (NRF2) is a master regulator in the cellular adaptive response
      to oxidative stress. The present study found that MIN6 beta-cells with stable
      knockdown of Nrf2 (Nrf2-KD) and islets isolated from Nrf2-knockout mice expressed
      substantially reduced levels of antioxidant enzymes in response to a variety of
      stressors. In scramble MIN6 cells or wild-type islets, acute exposure to
      oxidative stressors, including hydrogen peroxide (H2O2) and S-nitroso-N
      acetylpenicillamine, resulted in cell damage as determined by decrease in cell
      viability, reduced ATP content, morphology changes of islets, and/or alterations
      of apoptotic biomarkers in a concentration- and/or time-dependent manner. In
      contrast, silencing of Nrf2 sensitized MIN6 cells or islets to the damage. In
      addition, pretreatment of MIN6 beta-cells with NRF2 activators, including CDDO
      Im, dimethyl fumarate (DMF), and tert-butylhydroquinone (tBHQ), protected the
      cells from high levels of H2O2-induced cell damage. Given that reactive oxygen
      species (ROS) are involved in regulating glucose-stimulated insulin secretion
      (GSIS) and persistent activation of NRF2 blunts glucose-triggered ROS signaling
      and GSIS, the present study highlights the distinct roles that NRF2 may play in
      pancreatic beta-cell dysfunction that occurs in different stages of diabetes. 

PMID- 25949774
TI  - Trend and pattern of various types of cancer with special reference to gall
      bladder cancer in north bengal medical college, west bengal, India: a 3 years
      record based study.
AB  - BACKGROUND: Global burden of cancer is on rise and trends and pattern of cancers
      are rapidly changing different geographic and population groups. Gall bladder
      cancers are emerging with increasing proportion among select areas and groups and
      understanding these variations are important for appropriate strategies and
      interventions. However, absence of a well-developed universal cancer registry
      system in India, institution based secondary data analysis can generate useful
      information. The present study was conducted to determine the trend and pattern
      of cancer cases (with special reference to gall bladder cancer) treated in a
      tertiary care hospital in northern part of West Bengal. METHODS: Record based
      cross-sectional study was conducted in Department of Radiotherapy, North Bengal
      Medical College and Hospital. All newly registered cases between (2010 and 2012)
      were reviewed. RESULTS: A total of 2058 cancer cases were recorded during the 3
      year period. Of these, major types of cancers were oro-pharynx (16.1%), breast
      (15.4%), cervix (13.2%), lung (12.7%), gall bladder (6.5%) stomach cancer (6.4%),
      etc., Increasing proportions was observed for breast and gall bladder cancers.
      The proportion of gallbladder cancer cases in 2010, 2011, and 2012 were 3.8%,
      7.3% and 7.8%, respectively. Among 134 gall bladder cancer cases, 93.3% were
      females, 85.1% alcoholics, 57.4% had a history of fatty liver, 94% had
      adeno/adenosquamous carcinomas, and 65.7% were metastatic in nature. CONCLUSIONS:
      Increasing trend is observed in gall bladder cancer cases emphasizing the need
      for further large scale studies.

PMID- 25949775
TI  - Factors associated with the reporting of adverse drug reactions by health workers
      in nnewi Nigeria.
AB  - BACKGROUND: Under-reporting of adverse drug reactions (ADRs) by the prescribers
      is a common public health problem. Monitoring of factors that influence ADR
      reporting will reduce risks associated with drug use; improve patients care,
      safety and treatment outcome. The aim of this study was to determine the factors
      associated with the reporting of ADRs by health workers in Nnewi Nigeria.
      METHODS: A cross-sectional study of 372 health workers in different health
      facilities in Nnewi North Local Government Area of Anambra state, selected using
      multistage sampling technique was done. Data collection employed pretested, self
      administered structured questionnaires. Data were analyzed using Statistical
      Package for Social Sciences version 17. Tests of statistical significance were
      carried out using Chi-square tests for proportions. A P < 0.05 was considered
      significant. RESULTS: Out of the 372 respondents studied, 255 (68.5%) were
      females, and 117 (31.5%) were males. The modal age range (37.6%) was 31-40 years.
      Factors related by the respondents to influence ADR reporting include:
      Unavailability of electronic reporting (83.6%), unavailability of reporting forms
      (66.4%) and ignorance (58.2%). The difference among medical practitioners who
      related unavailability of electronic reporting process as obstacle to ADR
      reporting was not significant (P = 0.18). CONCLUSIONS: The study results revealed
      the factors associated with the reporting of ADRs among health workers in Nnewi
      Nigeria. It is desirable to initiate electronic reporting process, training
      programs on ADR reporting and make reporting forms/guidelines available to
      relevant health workers.

PMID- 25949776
TI  - Pattern of Caffeine Use among Teenagers in Bangalore, India: An Exploration.

PMID- 25949777
TI  - Effects of Probiotic Supplementation on Pancreatic beta-cell Function and C
      reactive Protein in Women with Polycystic Ovary Syndrome: A Randomized Double
      blind Placebo-controlled Clinical Trial.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a polygenic endocrine disorder in
      women of reproductive age that lead to infertility. The aim of this study was to
      investigate the effects of probiotic on pancreatic beta-cell function and C
      reactive protein (CRP) in PCOS patients. METHODS: This randomized double-blind
      placebo-controlled clinical trial was conducted among 72 women aged 15-40 years
      old diagnosed with PCOS. Participants were randomly assigned to two groups
      receiving: (1) Probiotic supplements (n = 36), (2) placebo (n = 36) for 8-week.
      Fasting blood samples were taken at baseline and after 8-week of intervention.
      RESULTS: Probiotic supplementation, compare with placebo, reduced fasting blood
      sugar (-4.15 +/- 2.87 vs. 2.57 +/- 5.66 mg/dL, respectively P = 0.7), serum
      insulin levels in crude model (-0.49 +/- 0.67 vs. 0.34 +/- 0.82 MUIU/mL,
      respectively, P = 0.09), homeostasis model of assessment-insulin resistance score
      (-0.25 +/- 0.18 vs. -0.05 +/- 0.18, respectively, P = 0.14) nonsignificantly.
      Serum insulin levels after adjustment with covariates reduced significantly in
      probiotic group (P = 0.02). We did not found any significant differences in mean
      changes of CRP between groups (-0.25 +/- 0.18 vs. -0.05 +/- 0.18, respectively, P
      = 0.14). CONCLUSIONS: A 8-week multispecies probiotics supplementation had
      nonsignificantly beneficial effect on pancreatic beta-cell function and CRP in
      PCOS patients. After adjustment for some covariates, serum insulin changes were
      significantly different between groups.

PMID- 25949778
TI  - Improving physical activity and metabolic syndrome indicators in women: a
      transtheoretical model-based intervention.
AB  - BACKGROUND: This study aimed at investigating the impact of an educational
      intervention based on transtheoretical model to increase physical activity and
      improve metabolic syndrome indicators in women. METHODS: In this quasi
      experimental study, 142 women with metabolic syndrome were randomly assigned to
      the case and control group (each group 71 participants). SECQ (Marcus), processes
      of change (Marcus), decisional balance (Bandura) and self-efficacy (Nigg)
      questionnaires and International Physical Activities Standard Questionnaire in
      preintervention, 3 and 6 months after intervention were completed. Furthermore,
      abdominal obesity, triglycerides (TG), and high-density lipoprotein (HDL) were
      measured. Physical activity intervention based on transtheoretical model (TTM)
      was performed in the case group. Finally, data were analyzed by SPSS (16) (SPSS
      Inc., Chicago, IL, USA) and repeated measure ANOVA, independent t-test and
      Freidman was used. A two-tailed P value, lower than 0.05, was considered to be
      statistically significant. RESULTS: After the intervention, physical activity
      level increased in the intervention group, and they also progressed in stages of
      change, but the people in the control group had regressed. All changes in TTM
      constructs were significant in the intervention group during the time and
      differences in pros and cons were not significant in the control group. Abdominal
      obesity and TG has significantly reduced, and HDL has increased in the
      intervention group. In the control group, there was a significant increase in TGs
      and a decrease in HDL. CONCLUSIONS: Physical activity training based on TTM can
      improve physical activity and metabolic syndrome indicators in women.

PMID- 25949779
TI  - Geographic distribution of cancer cases in isfahan province/2006-2010.
AB  - BACKGROUND: To facilitate analysis, interpreting and sharing cancer data and
      investigation spatial and geographical aspect of cancers in Isfahan province,
      cancer cases distribution was displayed using geographic information systems
      (GIS). METHODS: About 118,000 cancer data, which were confirmed in national
      cancer registration unit were extracted. Age-specific incidence rate and age
      standardized rate (ASR) of cancer cases from 2006 to 2010 was calculated for
      Isfahan province and its different districts. Distribution of ASR was determined
      according to sex and age groups. Spatial maps were drawn with the help of Arc GIS
      version 10 (ESRI, Redland, CA, USA) software in choropleth based maps. The data
      are classified in GIS environment by means of quantile method. Data were
      described with the help of maps spatially. RESULTS: Age standardized rate of
      cancers was higher in men than in women (134.58 vs. 115.4). The highest ASR was
      reported in the Isfahan (ASR: 133) and lowest in the Chadegan counties (ASR: 28).
      Different geographical distribution patterns of cancers were seen in district
      level. Cancer incidence was higher in the Isfahan, Lenjan, Fereidon Shahr and
      Falavarjan districts (134.3, 117.2, 113.5 and 111.1 respectively) among men and
      in Isfahan, Shahin Shahr, Lenjan and Najafabad districts (122.8, 102.3, 94 and 93
      respectively) among women. The incidence rates of most cancers were lowest in the
      North East region of the province compared to the rest of the region.
      CONCLUSIONS: Using GIS for visual displaying of cancers facilitated communication
      with the policymakers and community. This study provided hypotheses about
      differences in the incidence of cancer in Isfahan districts. Higher age-specific
      incidence rate in the Isfahan city is probably a reflection of problems in
      addressing the patients in cancer registration. Complementary studies are needed
      to evaluate lower ASR in the North East regions of the province.

PMID- 25949780
TI  - The concept of lifestyle factors, based on the teaching of avicenna (ibn sina).
AB  - According to the definition stated in the beginning of the "Al-Qanun fi al-Tibb"
      (the Qanun of Medicine); medicine is a science, from which one learns the states
      of the human body; health and disease and what causes them, in order to preserve
      good health when it exists, and restore it when it is lacking. Based on this
      issue, Avicenna believes that medical science belongs to all human without any
      limitation, and maintenance of health is one of its prime objectives. He states
      that many disorders are related to errors in the 6 factors, which are essential
      for maintaining health and preventing diseases. Avicenna described these six
      essential factors (lifestyle factors) in his masterpiece, Qanun of Medicine, as
      "Asbab-e-Settah-e-Zaruriah." Based on the teaching of Avicenna, the first step
      for maintaining health and approaches to treatment is modification of lifestyle
      factors, including of nutrition, physical activity, etc. 

PMID- 25949781
TI  - Association of adiponectin gene polymorphism with adiponectin levels and risk for
      insulin resistance syndrome.
AB  - BACKGROUND: Adiponectin is an abundant adipose tissue-derived protein with anti
      atherogenic, anti-inflammatory and antidiabetic properties. Plasma adiponectin
      levels are decreased in obesity, type 2 diabetes, and coronary artery disease and
      low adiponectin levels also predict insulin resistance (IR). METHODS: Case
      control study in which 642 male and female subjects were participated from the
      North Indian population. Lipid, insulin, leptin and adiponectin level were
      estimated using standard protocols by commercially available test kits. Single
      nucleotide polymorphisms +45T>G and +276G>T of the AMP1 (adiponectin) gene was
      genotyped by polymerase chain reaction restriction fragment length polymorphism
      method. RESULTS: Levels of adiponectin, insulin, homeostasis model assessment-IR
      index (HOMA-IR index), systolic blood pressure and fat mass showed significant
      differences between male and female subjects. Serum adiponectin level showed
      highly significant association with both the +45 and the +276 genotypes. The
      common haplotype triglyceride (TG) showed a significantly lower adiponectin value
      than other haplotypes (P = 0.0001). A clear trend of decreasing adiponectin
      levels per copy of the common haplotype was observed. Nonobese insulin sensitive
      subjects showed a higher adiponectin value (P = 0.0006) than nonobese insulin
      resistant subjects. The values of blood pressure, adiponectin, insulin, HOMA-IR,
      total-cholesterol, and low-density lipoprotein-cholesterol significantly
      associated with TG haplotype. CONCLUSIONS: We observed the very strong
      association of the adiponectin 45-276 genotypes and haplotypes with adiponectin
      levels in healthy north Indian population and TG haplotypes also associated with
      metabolic parameters of the IR syndrome.

PMID- 25949782
TI  - Cytomegalovirus, Toxoplasma gondii and Rubella Vertical Transmission Rates
      According to Mid-trimester Amniocentesis: A Retrospective Study.
AB  - OBJECTIVE: To examine vertical transmission rates of Cytomegalovirus, Toxoplasma
      Gondii and Rubella infections according to amniotic fluid PCR analysis. METHODS:
      A retrospective analysis of mid-trimester amniocenteses performed in in
      pregnancies with diagnosed maternal infection by Cytomegavirus (CMV), Rubella or
      Toxoplasma gondii during 1994-2008 was performed. Vertical transmission rates
      were observed according to the presence of the infectious agent's DNA in the
      amniotic fluid. A univariate regression model was also performed to investigate
      possible correlations between transmission and epidemiological parameters.
      RESULTS: Overall, 7033 amniocenteses were performed during study's period, of
      which 166 (2.4%) with the indication of maternal infection by CMV, Rubella or
      Toxoplasma. Mean maternal age was 27.4 +/- 2.5 years and the mean gestational age
      at amniocentesis was 18.7 +/- 2.5 weeks. Vertical transmission was observed in 21
      cases (12.7%). Transmission rate was 17.3% in cases with infection from CMV, 9.5%
      from Toxoplasma gondii and 7.8% from Rubella (P = .05). Maternal age was the only
      parameter being significantly associated with increased risk for vertical
      transmission (P = .04). CONCLUSIONS: According to our results, overall vertical
      transmission rate marginally exceeds 10%. CMV infection is characterized by
      relatively higher transplacental transmission rate, while increased maternal age
      appears to be associated with a higher risk for vertical transmission.

PMID- 25949783
TI  - High flow nasal cannula as a method for rapid weaning from nasal continuous
      positive airway pressure.
AB  - BACKGROUND: To compare two methods of weaning premature infants from nasal
      continuous positive airway pressure (NCPAP). METHODS: Between March and November
      2012, 88 preterm infants who were stable on NCPAP of 5 cmH2O with FIO2 <30% for a
      minimum of 6 h were randomly allocated to one of two groups. The high flow nasal
      cannula (HFNC) group received HFNC with flow of 2 L/min and FIO2 = 0.3 and then
      stepwise reduction of FIO2 and then flow. The non-HFNC group was maintained on
      NCPAP of 5 cmH2O and gradual reduction of oxygen until they were on FIO2 = 0.21
      for 6 h, and we had weaned them directly from NCPAP (with pressure of 5 cmH2O) to
      room air. RESULTS: No significant differences were found between 2 study groups
      with regards to gestational age, birth weight, Apgar score at 1 and 5 min after
      birth, patent ductus arteriosus and use of xanthines. The mean duration of oxygen
      therapy after randomization was significantly lower in HFNC group compared to non
      HFNC group (20.6 +/- 16.8 h vs. 49.6 +/- 25.3 h, P < 0.001). Also, the mean
      length of hospital stay was significantly lower in HFNC group compared to non
      HFNC group (11.3 +/- 7.8 days vs. 14.8 +/- 8.6 days, P = 0.04). The rate of
      successful weaning was not statistically different between two groups.
      CONCLUSIONS: Weaning from NCPAP to HFNC could decrease the duration of oxygen
      therapy and length of hospitalization in preterm infants.

PMID- 25949784
TI  - Effect of Circuit Resistance Training on Glycemic Control of Females with
      Diabetes Type II.
AB  - BACKGROUND: We aimed to assess effects of circuit resistance training (CRT) on
      glycemic control of females with Type II diabetes. METHODS: Twenty obese and
      overweight females with diabetes Type II were randomly selected in two groups
      (circuit resistance exercise and control). CRT performed in 3 days/week for 3
      months, and the serum and body parameters were assessed. Data were analyzed by
      Mann-Whitney U-test and Wilcoxon Signed-Rank test in SPSS version 19. RESULTS:
      Mean age in the CRT and control group was 50.2 +/- 4.89 years and 51.3 +/- 6.63
      years, respectively. Results showed significant changes in glycosylated
      hemoglobin (HbA1c) and subcutaneous fat were noted in the CRT group (P = 0.04, P
      = 0.002, respectively). Also, findings indicated higher HbA1c in CRT group after
      intervention in comparison with controls and results showed a significant
      difference (P = 0.04). CONCLUSIONS: According to the positive effect of CRT, it
      seems that can be recommended for patients with diabetes Type II.

PMID- 25949785
TI  - Formalizing biomedical concepts from textual definitions.
AB  - BACKGROUND: Ontologies play a major role in life sciences, enabling a number of
      applications, from new data integration to knowledge verification. SNOMED CT is a
      large medical ontology that is formally defined so that it ensures global
      consistency and support of complex reasoning tasks. Most biomedical ontologies
      and taxonomies on the other hand define concepts only textually, without the use
      of logic. Here, we investigate how to automatically generate formal concept
      definitions from textual ones. We develop a method that uses machine learning in
      combination with several types of lexical and semantic features and outputs
      formal definitions that follow the structure of SNOMED CT concept definitions.
      RESULTS: We evaluate our method on three benchmarks and test both the underlying
      relation extraction component as well as the overall quality of output concept
      definitions. In addition, we provide an analysis on the following aspects: (1)
      How do definitions mined from the Web and literature differ from the ones mined
      from manually created definitions, e.g., MeSH? (2) How do different feature
      representations, e.g., the restrictions of relations' domain and range, impact on
      the generated definition quality?, (3) How do different machine learning
      algorithms compare to each other for the task of formal definition generation?,
      and, (4) What is the influence of the learning data size to the task? We discuss
      all of these settings in detail and show that the suggested approach can achieve
      success rates of over 90%. In addition, the results show that the choice of
      corpora, lexical features, learning algorithm and data size do not impact the
      performance as strongly as semantic types do. Semantic types limit the domain and
      range of a predicted relation, and as long as relations' domain and range pairs
      do not overlap, this information is most valuable in formalizing textual
      definitions. CONCLUSIONS: The analysis presented in this manuscript implies that
      automated methods can provide a valuable contribution to the formalization of
      biomedical knowledge, thus paving the way for future applications that go beyond
      retrieval and into complex reasoning. The method is implemented and accessible to
      the public from: https://github.com/alifahsyamsiyah/learningDL.

PMID- 25949786
TI  - The effect of the muscle environment on the regenerative capacity of human
      skeletal muscle stem cells.
AB  - BACKGROUND: Muscle stem cell transplantation is a possible treatment for muscular
      dystrophy. In addition to the intrinsic properties of the stem cells, the local
      and systemic environment plays an important role in determining the fate of the
      grafted cells. We therefore investigated the effect of modulating the host muscle
      environment in different ways (irradiation or cryoinjury or a combination of
      irradiation and cryoinjury) in two immunodeficient mouse strains (mdx nude and
      recombinase-activating gene (Rag)2-/gamma chain-/C5-) on the regenerative
      capacity of two types of human skeletal muscle-derived stem cell (pericytes and
      CD133+ cells). METHODS: Human skeletal muscle-derived pericytes or CD133+ cells
      were transplanted into muscles of either mdx nude or recombinase-activating gene
      (Rag)2-/gamma chain-/C5- host mice. Host muscles were modulated prior to donor
      cell transplantation by either irradiation, or cryoinjury, or a combination of
      irradiation and cryoinjury. Muscles were analysed four weeks after
      transplantation, by staining transverse cryostat sections of grafted muscles with
      antibodies to human lamin A/C, human spectrin, laminin and Pax 7. The number of
      nuclei and muscle fibres of donor origin and the number of satellite cells of
      both host and donor origin were quantified. RESULTS: Within both host strains
      transplanted intra-muscularly with both donor cell types, there were
      significantly more nuclei and muscle fibres of donor origin in host muscles that
      had been modulated by cryoinjury, or irradiation+cryoinjury, than by irradiation
      alone. Irradiation has no additive effects in further enhancing the
      transplantation efficiency than cryodamage. Donor pericytes did not give rise to
      satellite cells. However, using CD133+ cells as donor cells, there were
      significantly more nuclei, muscle fibres, as well as satellite cells of donor
      origin in Rag2-/gamma chain-/C5- mice than mdx nude mice, when the muscles were
      injured by either cryodamage or irradiation+cryodamage. CONCLUSIONS: Rag2-/gamma
      chain-/C5- mice are a better recipient mouse strain than mdx nude mice for human
      muscle stem cell transplantation. Cryodamage of host muscle is the most effective
      method to enhance the transplantation efficiency of human skeletal muscle stem
      cells. This study highlights the importance of modulating the muscle environment
      in preclinical studies to optimise the efficacy of transplanted stem cells.

PMID- 25949787
TI  - Effect of levosimendan on the contractility of muscle fibers from nemaline
      myopathy patients with mutations in the nebulin gene.
AB  - BACKGROUND: Nemaline myopathy (NM), the most common non-dystrophic congenital
      myopathy, is characterized by generalized skeletal muscle weakness, often from
      birth. To date, no therapy exists that enhances the contractile strength of
      muscles of NM patients. Mutations in NEB, encoding the giant protein nebulin, are
      the most common cause of NM. The pathophysiology of muscle weakness in NM
      patients with NEB mutations (NEB-NM) includes a lower calcium-sensitivity of
      force generation. We propose that the lower calcium-sensitivity of force
      generation in NEB-NM offers a therapeutic target. Levosimendan is a calcium
      sensitizer that is approved for use in humans and has been developed to target
      cardiac muscle fibers. It exerts its effect through binding to slow
      skeletal/cardiac troponin C. As slow skeletal/cardiac troponin C is also the
      dominant troponin C isoform in slow-twitch skeletal muscle fibers, we
      hypothesized that levosimendan improves slow-twitch muscle fiber strength at
      submaximal levels of activation in patients with NEB-NM. METHODS: To test whether
      levosimendan affects force production, permeabilized slow-twitch muscle fibers
      isolated from biopsies of NEB-NM patients and controls were exposed to
      levosimendan and the force response was measured. RESULTS: No effect of
      levosimendan on muscle fiber force in NEB-NM and control skeletal muscle fibers
      was found, both at a submaximal calcium level using incremental levosimendan
      concentrations, and at incremental calcium concentrations in the presence of
      levosimendan. In contrast, levosimendan did significantly increase the calcium
      sensitivity of force in human single cardiomyocytes. Protein analysis confirmed
      that the slow skeletal/cardiac troponin C isoform was present in the skeletal
      muscle fibers tested. CONCLUSIONS: These findings indicate that levosimendan does
      not improve the contractility in human skeletal muscle fibers, and do not provide
      rationale for using levosimendan as a therapeutic to restore muscle weakness in
      NEB-NM patients. We stress the importance of searching for compounds that improve
      the calcium-sensitivity of force generation of slow-twitch muscle fibers. Such
      compounds provide an appealing approach to restore muscle force in patients with
      NEB-NM, and also in patients with other neuromuscular disorders.

PMID- 25949789
TI  - A reporter mouse for optical imaging of inflammation in mdx muscles.
AB  - BACKGROUND: Duchenne muscular dystrophy (DMD) is due to mutations in the gene
      coding for human DMD; DMD is characterized by progressive muscle degeneration,
      inflammation, fat accumulation, and fibrosis. The mdx mouse model of DMD lacks
      dystrophin protein and undergoes a predictable disease course. While this model
      has been a valuable resource for pre-clinical studies aiming to test therapeutic
      compounds, its utility is compromised by a lack of reliable biochemical tools to
      quantifiably assay muscle disease. Additionally, there are few non-invasive
      assays available to researchers for measuring early indicators of disease
      progression in mdx mice. METHODS: Mdx mice were crossed to knock-in mice
      expressing luciferase from the Cox2 promoter. These reporter mice (Cox2 (FLuc/+)
      DMD (-/-) ) were created to serve as a tool for researchers to evaluate muscle
      inflammation. Luciferase expression was assayed by immunohistochemistry to insure
      that it correlated with muscle lesions. The luciferase signal was quantified by
      optical imaging and luciferase assays to verify that the signal correlated with
      muscle damage. As proof of principle, Cox2 (FLuc/+) DMD (-/-) mice were also
      treated with prednisolone to validate that a reduction in luciferase signal
      correlated with prednisone treatment. RESULTS: In this investigation, a novel
      reporter mouse (Cox2 (FLuc/+) DMD (-/-) mice) was created and validated for non
      invasive quantification of muscle inflammation in vivo. In this dystrophic mouse,
      luciferase is expressed from cyclooxygenase 2 (Cox2) expressing cells and
      bioluminescence is detected by optical imaging. Bioluminescence is significantly
      enhanced in damaged muscle of exercised Cox2 (FLuc/+) DMD (-/-) mice compared to
      non-exercised Cox2 (FLuc/+) DMD (+/+) mice. Moreover, the Cox2 bioluminescent
      signal is reduced in Cox2 (FLuc/+) DMD (-/-) mice in response to a course of
      steroid treatment. Reduction in bioluminescence is detectable prior to measurable
      therapy-elicited improvements in muscle strength, as assessed by traditional
      means. Biochemical assay of luciferase provides a second means to quantify muscle
      inflammation. CONCLUSIONS: The Cox2 (FLuc/+) DMD (-/-) mouse is a novel tool to
      evaluate the therapeutic benefits of drugs intended to target inflammatory
      aspects of dystrophic pathology. This mouse model will be a useful adjunct to
      traditional outcome measures in assessing potential therapeutic compounds.

PMID- 25949788
TI  - Wnt/beta-catenin controls follistatin signalling to regulate satellite cell
      myogenic potential.
AB  - BACKGROUND: Adult skeletal muscle regeneration is a highly orchestrated process
      involving the activation and proliferation of satellite cells, an adult skeletal
      muscle stem cell. Activated satellite cells generate a transient amplifying
      progenitor pool of myoblasts that commit to differentiation and fuse into
      multinucleated myotubes. During regeneration, canonical Wnt signalling is
      activated and has been implicated in regulating myogenic lineage progression and
      terminal differentiation. METHODS: Here, we have undertaken a gene expression
      analysis of committed satellite cell-derived myoblasts to examine their ability
      to respond to canonical Wnt/beta-catenin signalling. RESULTS: We found that
      activation of canonical Wnt signalling induces follistatin expression in
      myoblasts and promotes myoblast fusion in a follistatin-dependent manner. In
      growth conditions, canonical Wnt/beta-catenin signalling prime myoblasts for
      myogenic differentiation by stimulating myogenin and follistatin expression. We
      further found that myogenin binds elements in the follistatin promoter and thus
      acts downstream of myogenin during differentiation. Finally, ectopic activation
      of canonical Wnt signalling in vivo promoted premature differentiation during
      muscle regeneration following acute injury. CONCLUSIONS: Together, these data
      reveal a novel mechanism by which myogenin mediates the canonical Wnt/beta
      catenin-dependent activation of follistatin and induction of the myogenic
      differentiation process.

PMID- 25949790
TI  - Pinocembrin suppresses TGF-beta1-induced epithelial-mesenchymal transition and
      metastasis of human Y-79 retinoblastoma cells through inactivating alphavbeta3
      integrin/FAK/p38alpha signaling pathway.
AB  - BACKGROUND: Pinocembrin is the most abundant flavonoid in propolis. In this
      study, we investigated the antimetastatic effect of pinocembrin on TGF-beta1
      induced epithelial-mesenchymal transition (EMT) and metastasis of human Y-79
      retinoblastoma cells. RESULTS: Firstly, the results showed that pinocembrin
      significantly suppresses the TGF-beta1-induced abilities of the invasion and
      migration of Y-79 cells under non-cytotoxic concentration. Pinocembrin decreased
      TGF-beta1-induced expression of vimentin, N-cadherin, alphav and beta3 integrin
      in Y-79 cells. Molecular data also showed pinocembrin inhibits the activation of
      focal adhesion kinase (FAK) and p38alpha signal involved in the downregulation of
      enzyme activities, protein and messenger RNA levels of matrix metalloproteinase
      2/9 (MMP-2/-9) induced by TGF-beta1. Next, pinocembrin also strongly inhibited
      the degradation of inhibitor of kappaBalpha (IkappaBalpha) and the nuclear levels
      of nuclear factor kappa B (NF-kappaB). Also, a dose-dependent inhibition on the
      binding ability of NF-kappaB was further observed under pinocembrin treatment.
      CONCLUSIONS: Presented results indicated that pinocembrin inhibits TGF-beta1
      induced epithelial-mesenchymal transition (EMT) and metastasis of Y-79 cells by
      inactivating the alphavbeta3 integrin/FAK/p38alpha signaling pathway. Thus, our
      findings point to the anticancer potential of pinocembrin against retinoblastoma
      cells.

PMID- 25949791
TI  - Thematic series: transcriptional regulation and disease.

PMID- 25949793
TI  - Functional Impact of RNA editing and ADARs on regulation of gene expression:
      perspectives from deep sequencing studies.
AB  - Cells regulate gene expression at multiple levels leading to a balance between
      robustness and complexity within their proteome. One core molecular step
      contributing to this important balance during metazoan gene expression is RNA
      editing, such as the co-transcriptional recoding of RNA transcripts catalyzed by
      the adenosine deaminse acting on RNA (ADAR) family of enzymes. Understanding of
      the adenosine-to-inosine RNA editing process has been broadened considerably by
      the next generation sequencing (NGS) technology, which allows for in-depth
      demarcation of an RNA editome at nucleotide resolution. However, critical issues
      remain unresolved with regard to how RNA editing cooperates with other transcript
      associated events to underpin regulated gene expression. Here we review the
      growing body of evidence, provided by recent NGS-based studies, that links RNA
      editing to other mechanisms of post-transcriptional RNA processing and gene
      expression regulation including alternative splicing, transcript stability and
      localization, and the biogenesis and function of microRNAs (miRNAs). We also
      discuss the possibility that systematic integration of NGS data may be employed
      to establish the rules of an "RNA editing code", which may give us new insights
      into the functional consequences of RNA editing. 

PMID- 25949792
TI  - Perturbations at the ribosomal genes loci are at the centre of cellular
      dysfunction and human disease.
AB  - Ribosomal RNA (rRNA) gene (rDNA) transcription by RNA Polymerase I (Pol I) drives
      cell growth and underlies nucleolar structure and function, indirectly
      coordinating many fundamental cellular processes. The importance of keeping rDNA
      transcription under tight control is reflected by the fact that deranged Pol I
      transcription is a feature of cancer and other human disorders. In this review,
      we discuss multiple aspects of rDNA function including the relationship between
      Pol I transcription and proliferative capacity, the role of Pol I transcription
      in mediating nucleolar structure and integrity, and rDNA/nucleolar interactions
      with the genome and their influence on heterochromatin and global genome
      stability. Furthermore, we discuss how perturbations in the structure of the rDNA
      loci might contribute to human disease, in some cases independent of effects on
      ribosome biogenesis. 

PMID- 25949794
TI  - Epigenetic regulation in cancer progression.
AB  - Cancer is a disease arising from both genetic and epigenetic modifications of DNA
      that contribute to changes in gene expression in the cell. Genetic modifications
      include loss or amplification of DNA, loss of heterozygosity (LOH) as well as
      gene mutations. Epigenetic changes in cancer are generally thought to be brought
      about by alterations in DNA and histone modifications that lead to the silencing
      of tumour suppressor genes and the activation of oncogenic genes. Other
      consequences that result from epigenetic changes, such as inappropriate
      expression or repression of some genes in the wrong cellular context, can also
      result in the alteration of control and physiological systems such that a normal
      cell becomes tumorigenic. Excessive levels of the enzymes that act as epigenetic
      modifiers have been reported as markers of aggressive breast cancer and are
      associated with metastatic progression. It is likely that this is a common
      contributor to the recurrence and spread of the disease. The emphasis on genetic
      changes, for example in genome-wide association studies and increasingly in whole
      genome sequencing analyses of tumours, has resulted in the importance of
      epigenetic changes having less attention until recently. Epigenetic alterations
      at both the DNA and histone level are increasingly being recognised as playing a
      role in tumourigenesis. Recent studies have found that distinct subgroups of poor
      prognosis tumours lack genetic alterations but are epigenetically deregulated,
      pointing to the important role that epigenetic modifications and/or their
      modifiers may play in cancer. In this review, we highlight the multitude of
      epigenetic changes that can occur and will discuss how deregulation of epigenetic
      modifiers contributes to cancer progression. We also discuss the off-target
      effects that epigenetic modifiers may have, notably the effects that histone
      modifiers have on non-histone proteins that can modulate protein expression and
      activity, as well as the role of hypoxia in epigenetic regulation. 

PMID- 25949796
TI  - The challenge of measuring multi-morbidity and its costs.
AB  - The ageing of the population across developed countries and beyond has increased
      the importance of examining multi-morbidity. The recent paper by Arbelle et al.
      [Isr J of Health Policy Res. 2014;3:29] on multiple chronic conditions in
      Israel's Maccabi Health Care System (MHC) is a welcome and interesting
      contribution to the literature on this topic. They found that the prevalence of
      multiple chronic conditions among the MHC population rises with age, is lower for
      higher socioeconomic groups, and is higher than in a primary care population in
      Scotland studied by Barnett et al. [Lancet. 2012;380:37-43]. The difference in
      prevalence between the two studies is unlikely to reflect entirely, or probably
      even mainly, real differences in morbidity rates between the two countries.
      Systematic reviews have highlighted large differences in the prevalence of multi
      morbidity in different studies. Although the Israeli and Scottish study used
      similar definitions and methods, the nature of the source data differed. It seems
      likely that the incentives to record the full range of patients' conditions may
      differ between data sources depending on the uses of the data, which may in turn
      depend on the country's health care financing system. If this is correct, it will
      complicate comparisons between different jurisdictions. It is important to
      consider not only the prevalence of multi-morbidity but also its costs to the
      health system and to wider society. Cost of illness studies can be helpful in
      informing decisions about prioritisation of resources. Multi-morbidity
      complicates such studies. The overall costs of health and social care for people
      with a specific condition would include costs relating to any comorbidities. To
      examine the marginal impact on overall costs of each condition among those with
      multiple conditions is likely to be complex and arguably not especially useful. 

PMID- 25949797
TI  - Inequalities in waiting times by socioeconomic status - a possible causal
      mechanism.
AB  - Much like waiting times for health services, the shortage of physicians and other
      health professionals poses a major health policy issue in many OECD countries. In
      this short commentary, I present indications that in Israel's periphery, the
      demand for advanced health services exceeds supply. This gap creates inequality
      in waiting times "across" geographical areas in the public sector and, moreover,
      could act as a causal mechanism of socioeconomic inequality. As a result,
      policymakers face two challenges: first, to increase the number of physicians in
      specialties and localities where there is a lack; and second, to take steps to
      enhance waiting time equality in areas of obvious shortages. 

PMID- 25949795
TI  - Dysregulated transcriptional and post-translational control of DNA
      methyltransferases in cancer.
AB  - Cancer is a leading cause of death worldwide. Aberrant promoter hypermethylation
      of CpG islands associated with tumor suppressor genes can lead to transcriptional
      silencing and result in tumorigenesis. DNA methyltransferases (DNMTs) are the
      enzymes responsible for DNA methylation and have been reported to be over
      expressed in various cancers. This review highlights the current status of
      transcriptional and post-translational regulation of the DNMT expression and
      activity with a focus on dysregulation involved in tumorigenesis. The
      transcriptional up-regulation of DNMT gene expression can be induced by Ras-c-Jun
      signaling pathway, Sp1 and Sp3 zinc finger proteins and virus oncoproteins.
      Transcriptional repression on DNMT genes has also been reported for p53, RB and
      FOXO3a transcriptional regulators and corepressors. In addition, the low
      expressions of microRNAs 29 family, 143, 148a and 152 are associated with DNMTs
      overexpression in various cancers. Several important post-translational
      modifications including acetylation and phosphorylation have been reported to
      mediate protein stability and activity of the DNMTs especially DNMT1. In this
      review, we also discuss drugs targeting DNMT protein expression and activation
      for therapeutic strategy against cancer. 

PMID- 25949798
TI  - Enhancing patient-doctor-computer communication in primary care: towards
      measurement construction.
AB  - OBJECTIVE: The traditional dyadic dynamics of the medical encounter has been
      altered into a triadic relationship by introducing the computer into the
      examination room. This study defines Patient-Doctor-Computer Communication (PDCC)
      as a new construct and provides an initial validation process of an instrument
      for assessing PDCC in the computerized exam room: the e-SEGUE. MATERIAL AND
      METHODS: Based on the existing literature, a new construct, PDCC, is defined as
      the physician's ability to provide patient-centered care while using the computer
      during the medical encounter. This study elucidates 27 PDCC-related behaviors
      from the relevant literature and state of the art models of PDCC. These were
      embedded in the SEGUE communication assessment framework to form the e-SEGUE, a
      communication skills assessment tool that integrates computer-related
      communication skills. Based on Mackenzie et al.'s methodological approach of
      measurement construction, we conducted a two-phased content validity analysis by
      a general and expert panels of the PDCC behaviors represented in the e-SEGUE.
      This study was carried out in an environment where EMR use is universal and fully
      integrated in the physicians' workflow. RESULTS: The panels consisted of medical
      students, residents, primary care physicians, healthcare leaders and faculty of
      medicine members, who rated and provided input regarding the 27 behaviors.
      Overall, results show high level of agreement with 23 PDCC-related behaviors.
      CONCLUSION: The PDCC instrument developed in this study, the e-SEGUE, fared well
      in a rigorous, albeit initial, validation process has a unique potential for
      training and enhancing patient-doctor communication (PDC) in the computerized
      examination room pending further development.

PMID- 25949799
TI  - Assigning Israeli medical graduates to internships.
AB  - BACKGROUND: Physicians in Israel are required to do an internship in an
      accredited hospital upon completion of the medical studies, and prior to
      receiving the medical license. For most students, the assignment is determined by
      a lottery, which takes into consideration the preferences of these students.
      OBJECTIVES: We propose a novel way to perform this lottery, in which (on average)
      a larger number of students gets one of their top choices. We report about
      implementing this method in the 2014 Internship Lottery in Israel. METHODS: The
      new method is based on calculating a tentative lottery, in which each student has
      some probability of getting to each hospital. Then a computer program "trades"
      between the students, where trade is performed only if it is beneficial to both
      sides. This trade creates surplus, which translates to more students getting one
      of their top choices. RESULTS: The average student improved his place by 0.91
      seats. CONCLUSIONS: The new method can improve the welfare of medical graduates,
      by giving them more probability to get to one of their top choices. It can be
      applied in internship markets in other countries as well.

PMID- 25949801
TI  - Magnetic resonance imaging appearance of hypertensive encephalopathy in a dog.
AB  - A 16-year-old female spayed English Staffordshire terrier was presented for
      evaluation of a 10-month history of intermittent myoclonic episodes, and a one
      weeks history of short episodes of altered mentation, ataxia and collapse.
      Magnetic resonance imaging identified subcortical oedema, predominately in the
      parietal and temporal lobes and multiple cerebral microbleeds. Serum
      biochemistry, indirect blood pressure measurements and magnetic resonance imaging
      abnormalities were consistent with hypertensive encephalopathy secondary to
      chronic kidney disease. 

PMID- 25949800
TI  - US chiropractors' attitudes, skills and use of evidence-based practice: A cross
      sectional national survey.
AB  - BACKGROUND: Evidence based practice (EBP) is being increasingly utilized by
      health care professionals as a means of improving the quality of health care. The
      introduction of EBP principles into the chiropractic profession is a relatively
      recent phenomenon. There is currently a lack of information about the EBP
      literacy level of US chiropractors and the barriers/facilitators to the use of
      EBP in the chiropractic profession. METHODS: A nationwide EBP survey of US
      chiropractors was administered online (Nov 2012-Mar 2013) utilizing a validated
      self-report instrument (EBASE) in which three sub-scores are reported: attitudes,
      skills and use. Means, medians, and frequency distributions for each of the sub
      scores were generated. Descriptive statistics were used to analyze the
      demographic characteristics of the sample. Means and proportions were calculated
      for all of the responses to each of the questions in the survey. RESULTS: A total
      of 1,314 US chiropractors completed the EBASE survey; the sample appeared to be
      representative of the US chiropractic profession. Respondents were predominantly
      white (94.3%), male (75%), 47 (+/- 11.6) years of age, and in practice for more
      than 10 years (60%). EBASE sub-score means (possible ranges) were: attitudes,
      31.4 (8-40); skills, 44.3 (13-65); and use, 10.3 (0-24). Survey participants
      generally held favorable attitudes toward EBP, but reported less use of EBP. A
      minority of participants indicated that EBP coursework (17%) and critical
      thinking (29%) were a major part of their chiropractic education. The most
      commonly reported barrier to the use of EBP was "lack of time". Almost 90% of the
      sample indicated that they were interested in improving their EBP skills.
      CONCLUSION: American chiropractors appear similar to chiropractors in other
      countries, and other health professionals regarding their favorable attitudes
      towards EBP, while expressing barriers related to EBP skills such as research
      relevance and lack of time. This suggests that the design of future EBP
      educational interventions should capitalize on the growing body of EBP
      implementation research developing in other health disciplines. This will likely
      include broadening the approach beyond a sole focus on EBP education, and taking
      a multilevel approach that also targets professional, organizational and health
      policy domains.

PMID- 25949803
TI  - Adherence to Artemisinin Combination Therapy for the treatment of uncomplicated
      malaria in the Democratic Republic of the Congo.
AB  - Between 2011 and 2013 the number of recorded malaria cases had more than doubled,
      and between 2009 and 2013 had increased almost 4-fold in MSF-OCA (Medecins sans
      Frontieres - Operational Centre Amsterdam) programmes in the Democratic Republic
      of the Congo (DRC). The reasons for this rise are unclear. Incorrect intake of
      Artemisinin Combination Therapy (ACT) could result in failure to treat the
      infection and potential recurrence. An adherence study was carried out to assess
      whether patients were completing the full course of ACT. One hundred and eight
      malaria patients in Shamwana, Katanga province, DRC were visited in their
      households the day after ACT was supposed to be completed. They were asked a
      series of questions about ACT administration and the blister pack was observed
      (if available). Sixty seven (62.0%) patients were considered probably adherent.
      This did not take into account the patients that vomited or spat their pills or
      took them at the incorrect time of day, in which case adherence dropped to 46
      (42.6%). The most common reason that patients gave for incomplete/incorrect
      intake was that they were vomiting or felt unwell (10 patients (24.4%), although
      the reasons were not recorded for 22 (53.7%) patients). This indicates that there
      may be poor understanding of the importance of completing the treatment or that
      the side effects of ACT were significant enough to over-ride the pharmacy
      instructions. Adherence to ACT was poor in this setting. Health education
      messages emphasising the need to complete ACT even if patients vomit doses, feel
      unwell or their health conditions improve should be promoted. 

PMID- 25949802
TI  - Visualisation of BioPAX Networks using BioLayout Express (3D).
AB  - BioLayout Express (3D) is a network analysis tool designed for the visualisation
      and analysis of graphs derived from biological data. It has proved to be powerful
      in the analysis of gene expression data, biological pathways and in a range of
      other applications. In version 3.2 of the tool we have introduced the ability to
      import, merge and display pathways and protein interaction networks available in
      the BioPAX Level 3 standard exchange format. A graphical interface allows users
      to search for pathways or interaction data stored in the Pathway Commons
      database. Queries using either gene/protein or pathway names are made via the
      cPath2 client and users can also define the source and/or species of information
      that they wish to examine. Data matching a query are listed and individual
      records may be viewed in isolation or merged using an 'Advanced' query tab. A
      visualisation scheme has been defined by mapping BioPAX entity types to a range
      of glyphs. Graphs of these data can be viewed and explored within BioLayout as 2D
      or 3D graph layouts, where they can be edited and/or exported for visualisation
      and editing within other tools. 

PMID- 25949804
TI  - Finding small molecules for the 'next Ebola'.
AB  - The current Ebola virus epidemic may provide some suggestions of how we can
      better prepare for the next pathogen outbreak. We propose several cost effective
      steps that could be taken that would impact the discovery and use of small
      molecule therapeutics including: 1. text mine the literature, 2. patent assignees
      and/or inventors should openly declare their relevant filings, 3. reagents and
      assays could be commoditized, 4. using manual curation to enhance database links,
      5. engage database and curation teams, 6. consider open science approaches, 7.
      adapt the "box" model for shareable reference compounds, and 8. involve the
      physician's perspective. 

PMID- 25949805
TI  - Digital teaching tools and global learning communities.
AB  - In 2009, we started a project to support the teaching and learning of university
      level plant sciences, called Teaching Tools in Plant Biology. Articles in this
      series are published by the plant science journal, The Plant Cell (published by
      the American Society of Plant Biologists). Five years on, we investigated how the
      published materials are being used through an analysis of the Google Analytics
      pageviews distribution and through a user survey. Our results suggest that this
      project has had a broad, global impact in supporting higher education, and also
      that the materials are used differently by individuals in terms of their role
      (instructor, independent learner, student) and geographical location. We also
      report on our ongoing efforts to develop a global learning community that
      encourages discussion and resource sharing. 

PMID- 25949806
TI  - Military-specific application of nutritional supplements: a brief overview.
AB  - The Soldiers of America's military endure numerous physical and mental challenges
      that demand strict physical fitness regimens, extreme mental agility, and a
      perpetual readiness to deploy at a moment's notice. The chronicity of these
      stressors has the potential to dramatically reduce performance - both directly
      and indirectly.  Because of this risk, many Soldiers turn to nutritional
      supplements with hopes of optimizing performance. Increasing amounts of research
      have demonstrated that various supplements may enhance overall physical prowess,
      health, and offer quicker recovery in the face of corporal or psychological
      extremes. Most individuals, including many medical and nutrition professionals,
      possess only an elementary comprehension of nutritional supplements and their
      effect on Soldiers in training or combat environments. Nevertheless, a grasp of
      these details is required for safety and optimal benefits. Various compounds have
      been evaluated - to include evidence within the military setting - and found to
      augment endurance, increase cognitive function, decrease knee pain, or offer
      hearing or lung protection in the face of high-energy impulses. These efficacious
      outcomes may serve to augment the health and longevity of these Soldiers;
      however, continued research is needed for efficacy and long-term safety within
      specific environments. 

PMID- 25949807
TI  - Weak and contradictory effects of self-medication with nectar nicotine by
      parasitized bumblebees.
AB  - The presence of antimicrobial secondary metabolites in nectar suggests that
      pollinators, which are threatened globally by emergent disease, may benefit from
      the consumption of nectars rich in these metabolites. We tested whether nicotine,
      a nectar secondary metabolite common in Solenaceae and Tilia species, is used by
      parasitized bumblebees as a source of self-medication , using a series of
      toxicological, microbiological and behavioural experiments. Caged bees infected
      with Crithidia bombi [TI1] had a slight preference for sucrose solution laced
      with the alkaloid and behavioural tests showed that the parasite infection
      induced an increased consumption of nicotine during foraging activity. When
      ingested, nicotine delayed the progression of a gut infection in bumblebees by a
      few days, but dietary nicotine did not clear the infection, and after 10 days the
      parasite load approached that of control bees. Moreover, when pathogens were
      exposed to the alkaloid prior to host ingestion the protozoan's viability was not
      directly affected, suggesting that anti-parasite effects were relatively weak.
      Nicotine consumption in a single dose did not impose any cost even in food
      stressed bees (starved) but the alkaloid had detrimental effects on healthy bees
      if consistently consumed for weeks. These toxic effects disappeared in infected
      bees suggesting that detoxification costs might have been counterbalanced by the
      advantages in slowing the progression of the infection. Nonetheless we did not
      find a benefit of nicotine consumption in terms of life expectancy of infected
      bees, making these findings difficult to interpret. Our results indicate that
      caution is warranted in interpreting impacts of plant metabolites on insect
      parasites and suggest that the conditions under which nicotine consumption
      provides benefits to either bees or plants remain to be identified. The
      contention that secondary metabolites in nectar may be under selection from
      pollinators, or used by plants to enhance their own reproductive success, remains
      to be confirmed. 

PMID- 25949808
TI  - Follow-up: Prospective compound design using the 'SAR Matrix' method and matrix
      derived conditional probabilities of activity.
AB  - In a previous Method Article, we have presented the 'Structure-Activity
      Relationship (SAR) Matrix' (SARM) approach. The SARM methodology is designed to
      systematically extract structurally related compound series from screening or
      chemical optimization data and organize these series and associated SAR
      information in matrices reminiscent of R-group tables. SARM calculations also
      yield many virtual candidate compounds that form a "chemical space envelope"
      around related series. To further extend the SARM approach, different methods are
      developed to predict the activity of virtual compounds. In this follow-up
      contribution, we describe an activity prediction method that derives conditional
      probabilities of activity from SARMs and report representative results of first
      prospective applications of this approach. 

PMID- 25949809
TI  - Mitochondrial responses to extreme environments: insights from metabolomics.
AB  - Humans are capable of survival in a remarkable range of environments, including
      the extremes of temperature and altitude as well as zero gravity. Investigation
      into physiological function in response to such environmental stresses may help
      further our understanding of human (patho-) physiology both at a systems level
      and in certain disease states, making it a highly relevant field of study. This
      review focuses on the application of metabolomics in assessing acclimatisation to
      these states, particularly the insights this approach can provide into
      mitochondrial function. It includes an overview of metabolomics and the
      associated analytical tools and also suggests future avenues of research. 

PMID- 25949813
TI  - Rethinking the withholding/withdrawing distinction: the cultural construction of
      "life-support" and the framing of end-of-life decisions.
AB  - This paper is a theoretical and empirically informed examination of the
      naturalist distinction between withholding and withdrawing life-support. Drawing
      on the history of mechanical ventilation and on a recent Israeli law containing a
      novel approach to disconnecting life-support at the end of life, it is argued
      that the design of machines predicates the division line between "active" and
      "passive" interventions, and that the distinction itself might be morally self
      defeating. Informed by insights from moral psychology, behavioral economics and
      philosophies of technology, the paper warns against the placement of this old
      distinction at the heart of the moral and legal regulation of life-support at the
      end of life. 

PMID- 25949811
TI  - Large-scale analysis of the evolutionary histories of phosphorylation motifs in
      the human genome.
AB  - BACKGROUND: Protein phosphorylation is a post-translational modification that is
      essential for a wide range of eukaryotic physiological processes, such as
      transcription, cytoskeletal regulation, cell metabolism, and signal transduction.
      Although more than 200,000 phosphorylation sites have been reported in the human
      genome, the physiological roles of most remain unknown. In this study, we provide
      some useful datasets for the assessment of functional phosphorylation signaling
      using a comparative genome analysis of phosphorylation motifs. FINDINGS: We
      described the evolutionary patterns of conservation of these and comparative
      genomic data for 93,101 phosphosites and 1,003,756 potential phosphosites in
      human phosphomotifs, using 178 phosphomotifs identified in a previous study that
      occupied 69% of known phosphosites in public databases. Comparative genomic
      analyses were performed using genomes from nine species from yeast to humans.
      Here we provide an overview of the evolutionary patterns of phosphomotif
      acquisition and indicate the dependence on motif structures. Using the data from
      our previous study, we describe the interaction networks of phosphoproteins,
      identify the kinase substrates associated with phosphoproteins, and perform gene
      ontology enrichment analyses. In addition, we show how this dataset can help to
      elucidate the function of phosphomotifs. CONCLUSIONS: Our characterizations of
      motif structures and assessments of evolutionary conservation of phosphosites
      reveal physiological roles of unreported phosphosites. Thus, interactions between
      protein groups that share motifs are likely to be helpful for inferring kinase
      substrate interaction networks. Our computational methods can be used to
      elucidate the relationships between phosphorylation signaling and cellular
      functions.

PMID- 25949814
TI  - Much caution does no harm! Organophosphate poisoning often causes pancreatitis.
AB  - Organophosphate poisoning (OP) results in various poisoning symptoms due to its
      strong inhibitory effect on cholinesterase. One of the occasional complications
      of OP is pancreatitis. A 62-year-old woman drank alcohol and went home at
      midnight. After she quarreled with her husband and drank 100 ml of malathion, a
      parasympathomimetic organophosphate that binds irreversibly to cholinesterase,
      she was transported to our hospital in an ambulance. On admission, activated
      charcoal, magnesium citrate, and pralidoxime methiodide (PAM) were used for
      decontamination after gastric lavage. Abdominal computed tomography detected
      edema of the small intestine and colon with doubtful bowel ischemia, and acute
      pancreatitis was suspected. Arterial blood gas analysis revealed severe lactic
      acidosis. The Ranson score was 6 and the APACHE II (Acute Physiology and Chronic
      Health Evaluation) score was 14. Based on these findings, severe acute
      pancreatitis was diagnosed. One day after admission, hemodiafiltration (HDF) was
      started for the treatment of acute pancreatitis. On the third hospital day, OP
      symptoms were exacerbated, with muscarinic manifestations including bradycardia
      and hypersalivation and decreased plasma cholinesterase activity. Atropine was
      given and the symptoms improved. The patient's general condition including
      hemodynamic status improved. Pancreatitis was attenuated by 5 days of HDF.
      Ultimately, it took 14 days for acute pancreatitis to improve, and the patient
      discharged on hospital day 32. Generally, acute pancreatitis associated with OP
      is mild. In fact, one previous report showed that the influence of
      organophosphates on the pancreas disappears in approximately 72 hours, and
      complicated acute pancreatitis often improves in 4-5 days. However, it was
      necessary to treat pancreatitis for more than 2 weeks in this case. Therefore,
      organophosphate-associated pancreatitis due to malathion is more severe. Although
      OP sometime causes severe necrotic pancreatitis or pancreatic pseudocysts, it was
      thought that the present patient had a good clinical course without these
      complications due to the appropriate intensive care including nafamostat,
      antibiotics, fluid resuscitation, and HDF. In conclusion, OP-associated
      pancreatitis requires careful assessment because it may be aggravated, as in this
      case. 

PMID- 25949812
TI  - Direct reprogramming of induced neural progenitors: a new promising strategy for
      AD treatment.
AB  - Alzheimer's disease (AD) is a prominent form of dementia, characterized by
      aggregation of the amyloid beta-peptide (Abeta) plaques and neurofibrillary
      tangles, loss of synapses and neurons, and degeneration of cognitive functions.
      Currently, although a variety of medications can relieve some of the symptoms,
      there is no cure for AD. Recent breakthroughs in the stem cell field provide
      promising strategies for AD treatment. Stem cells including embryonic stem cells
      (ESCs), neural stem cells (NSCs), mesenchymal stem cells (MSCs), and induced
      pluripotent stem cells (iPSCs) are potentials for AD treatment. However, the
      limitation of cell sources, safety issues, and ethical issues restrict their
      applications in AD. Recently, the direct reprogramming of induced neural
      progenitor cells (iNPCs) has shed light on the treatment of AD. In this review,
      we will discuss the latest progress, challenges, and potential applications of
      direct reprogramming in AD treatment. 

PMID- 25949815
TI  - Lactococcus garvieae endocarditis in a native valve identified by MALDI-TOF MS
      and PCR-based 16s rRNA in Spain: A case report.
AB  - Lactococcus garvieae is a Gram-positive, catalase negative coccus arranged in
      pairs or short chains, well-known as a fish pathogen. We report a case of
      Infective Endocarditis (IE) by L. garvieae in a native valve from a 68-year-old
      male with unknown history of contact with raw fish and an extensive history of
      heart disease. This case highlights the reliability of MALDI-TOF MS compared to
      conventional methods in the identification of rare microorganisms like this. 

PMID- 25949816
TI  - Utilization of oral antidiabetic medications in Taiwan following strategies to
      promote access to medicines for chronic diseases in community pharmacies.
AB  - OBJECTIVES: Taiwan's National Health Insurance (NHI) has encouraged physicians to
      use "chronic medication prescriptions" for patients with stable chronic diseases
      since 1995. Patients are allowed to refill such prescriptions at community
      pharmacies for a maximum of three months' supply of medications without
      revisiting the doctor. In 2006, NHI initiated strategies targeting the public,
      doctors, and healthcare facilities to enhance the overall rate of chronic
      medication prescriptions, aiming to achieve 30% by 2010. We examined prescribing
      and dispensing of oral antidiabetic drugs from 2001 to 2010, before and after the
      start of the promotion strategies for chronic medication prescriptions in 2006.
      METHODS: Using outpatient care data from the NHI database and the interrupted
      time series design, we analyzed changes in rate of chronic medication
      prescriptions, share of prescriptions filled at community pharmacies, and share
      of reimbursed expenditures accounted by community pharmacies. RESULTS: During
      2001-2010, the rate of chronic medication prescriptions for diabetes increased
      steadily by about 3% per year (from 3.5% to 26.2%). Three years after the
      promotion strategies, there was a non-significant reduction of 8.7% (95%
      confidence interval [CI]: -17.35%, 0.05%) in the rate of chronic medication
      prescriptions but increases in prescription refills at community pharmacies and
      associated reimbursed expenditures: 12.8% (95% C.I.:1.66%, 23.98%) and 15.8% (95%
      C.I.: -1.35%, 33.02%) respectively. CONCLUSIONS: While rate of chronic medication
      prescriptions was not significantly affected by the 2006 promotion strategy,
      shares of prescriptions refilled at community pharmacies and associated
      expenditures increased slightly but significantly.

PMID- 25949817
TI  - Monitoring and assessment of water health quality in the Tajan River, Iran using
      physicochemical, fish and macroinvertebrates indices.
AB  - BACKGROUND: Nowadays, aquatic organisms are used as bio-indicators to assess
      ecological water quality in western regions, but have hardly been used in an
      Iranian context. We, therefore, evaluated the suitability of several indices to
      assess the water quality for an Iranian case study. METHODS: Measured data on
      biotic (fish and macroinvertebrates) and abiotic elements (28 physicochemical and
      habitat parameters), were used to calculate six indices for assessment of water
      quality and the impact of human activities in the Tajan river, Iran. GIS, uni-
      and multivariate statistics were used to assess the correlations between
      biological and environmental endpoints. RESULTS: The results showed that
      ecological condition and water quality were reduced from up- to downstream. The
      reduced water quality was revealed by the biotic indices better than the abiotic
      ones which were linked to a variety of ecological water quality scales.
      CONCLUSION: The fish index showed a strong relationship with long-term database
      of physicochemical parameters (12 years (94%)), whereas macroinvertebrates index
      is more correlated with short-term data (76%). Meanwhile, the biotic and abiotic
      elements in this study were also classified well by PCA. Pulp and wood plants and
      sand mining are indicated to have the most negative effects on the river
      ecosystem.

PMID- 25949818
TI  - Role of vascular function in predicting arteriovenous fistula outcomes: an
      observational pilot study.
AB  - BACKGROUND: Many arteriovenous fistula (AVF) fail prior to use due to lack of
      maturation or thrombosis. Determining vascular function prior to surgery may be
      helpful to predict subsequent AVF success. This is a feasibility study to
      describe the vascular function in a cohort of chronic kidney disease (CKD)
      patients who are awaiting AVF creation. METHODS: A prospective cohort of 28 CKD
      patients expected to progress to HD underwent arterial stiffness (pulse wave
      velocity, PWV) and endothelial function testing (flow mediated dilation FMD, and
      peripheral arterial tonometry, PAT) one week prior to AVF creation. AVF success
      was defined as maintaining patency and achieving maturation. Post operative
      fistula assessment at 8 weeks evaluated maturation (clinical assessment of
      adequate fistula flowand ultrasound diameter >= 0.5 cm). RESULTS: The median age
      72 years (62 - 78), 75% males, eGFR 15 ml/min/1.73 m(2) (12 - 18). 20 (71%)
      patients had successful AVF surgery with a mature AVF at 8 weeks. Patients with
      AVF success had higher mean PAT values 1.87 +/- 0.52 than those with failed AVF
      1.41 +/- 0.24 p = 0.03. CONCLUSIONS: Microvascular endothelial function as
      measured using PAT may be useful as a predictor of AVF maturation and function.
      This simple non invasive marker of vascular function may be a useful tool to
      predict AVF outcomes.

PMID- 25949819
TI  - Breakdown in the organ donation process and its effect on organ availability.
AB  - Background. This study examines the effect of breakdown in the organ donation
      process on the availability of transplantable organs. A process breakdown is
      defined as a deviation from the organ donation protocol that may jeopardize organ
      recovery. Methods. A retrospective analysis of donation-eligible decedents was
      conducted using data from an independent organ procurement organization. Adjusted
      effect of process breakdown on organs transplanted from an eligible decedent was
      examined using multivariable zero-inflated Poisson regression. Results. An
      eligible decedent is four times more likely to become an organ donor when there
      is no process breakdown (adjusted OR: 4.01; 95% CI: 1.6838, 9.6414; P < 0.01)
      even after controlling for the decedent's age, gender, race, and whether or not a
      decedent had joined the state donor registry. However once the eligible decedent
      becomes a donor, whether or not there was a process breakdown does not affect the
      number of transplantable organs yielded. Overall, for every process breakdown
      occurring in the care of an eligible decedent, one less organ is available for
      transplant. Decedent's age is a strong predictor of likelihood of donation and
      the number of organs transplanted from a donor. Conclusion. Eliminating
      breakdowns in the donation process can potentially increase the number of organs
      available for transplant but some organs will still be lost. 

PMID- 25949820
TI  - Association of birth parameters with refractive status in a sample of caucasian
      children aged 4-17 years.
AB  - Purpose. To investigate the association of birth parameters with refractive
      status in different age groups of Caucasian children. Materials and Methods. This
      cross-sectional study included 564 eyes of 282 children aged 4 to 17 years. All
      children underwent complete ophthalmologic examination. The children were divided
      into three groups according to their refractive status (emmetropia,myopia, and
      hyperopia), ages (4-7, 8-9, 10-12, and 13-17), and appropriateness for
      gestational age, respectively. Results. The mean age of the children was 9.2 +/-
      2.8 (age range 4-17 years). The mean spheric equivalent was +0.3 +/- 1.7 (range:
      (-10.0)-(+10.0) diopters). The mean birth weight and gestational age were 2681.1
      +/- 930.8 grams (750-5000 grams) and 37.2 +/- 3.7 weeks (25-42 weeks). According
      to multinominal logistic regression analysis, children with myopia were more
      likely to have higher birth weights than emmetropic children (OR: 1.0, 95% CI:
      1.000-1.001, and P = 0.028). The hypermetropes were found to be significantly
      small for gestational age between 13 and 17 years of age. Conclusion. Birth
      weight and appropriateness for gestational age as birth parameters may have an
      impact on development of all types of refractive errors. The hypermetropic
      children tended to be small for gestational age. 

PMID- 25949821
TI  - Endoscopic endonasal dacryocystorhinostomy combined with canaliculus repair for
      the management of dacryocystitis with canalicular obstruction.
AB  - Purpose. The aim of this study is to propose a simple and efficient combination
      surgery for the management of dacryocystitis with canalicular obstruction.
      Methods. A retrospective noncomparative case series of dacryocystitis with
      canalicular obstruction has been studied. Twelve patients with dacryocystitis and
      canalicular obstruction underwent a conventional endoscopic endonasal
      dacryocystorhinostomy (EE-DCR) combined with a modified canalicular repair.
      Postoperative observations included slit lamp, fluorescein dye disappearance
      test, lacrimal syringing, lacrimal endoscopy, and nasal endoscopy. Results. After
      6-18 months of postoperative follow-up, the symptoms of epiphora and mucopurulent
      discharge disappeared completely in 10 patients, and occasional or intermittent
      epiphora remained in 2 patients. All of the twelve patients showed an opened
      intranasal ostium and normal fluorescein dye disappearance test. Patent
      bicanalicular irrigation was achieved in 9 patients. One patient had a partial
      and the other two had a complete reobstruction by lacrimal irrigation to their
      repaired lower canaliculus; however, all of them had a patent lacrimal irrigation
      to upper canaliculus. The functional success rate for the combination surgery is
      83% (10/12), and anatomical success rate is 75% (9/12). Conclusion. EE-DCR
      combined with modified canalicular repair is a simple and efficient method for
      the management of dacryocystitis with canalicular obstruction. 

PMID- 25949822
TI  - Comparison of two anesthetic methods for intravitreal ozurdex injection.
AB  - Purpose. To determine whether subconjunctival lidocaine injection maintains
      additional anesthetic effect during intravitreal Ozurdex injection. Methods. 63
      patients who were diagnosed as central or branch retinal vein occlusion and
      planned to receive Ozurdex injection for macular edema were prospectively
      included in the study. The patients were randomized into one of the two
      anesthetic groups. The first group received topical proparacaine drop and
      lidocaine applied pledget. The second group received subconjunctival lidocaine
      injection in addition to the anesthetics in group 1. Results. Mean pain score was
      1.90 +/- 2.39 in group 1 and 1.71 +/- 2.09 in group 2 (p = 0.746). Mean
      subconjunctival hemorrhage grade was 1.67 +/- 0.17 in group 1 and 0.90 +/- 0.14
      in group 2 (p = 0.001). There was no relationship between the amount of
      subconjunctival hemorrhage and pain score of the patients. Conclusions. There was
      no difference in pain scores between the two anesthetic methods. The addition of
      subconjunctival lidocaine injection offered no advantage in pain relief compared
      to lidocaine-applied pledgets. 

PMID- 25949824
TI  - Identifying state resources and support programs on e-government websites for
      persons with intellectual and developmental disabilities.
AB  - This descriptive cross-sectional study identified resources and programs that are
      available nationwide on the Internet to support individuals and families with
      intellectual and developmental disabilities (I/DD), with a focus on intellectual
      disability. This evaluation included easily identifiable information on specific
      resources and highlighted unique programs found in individual states that were
      linked from e-government websites. Researchers documented the ease of access and
      available information for all 50 states and the District of Columbia. A number of
      disparities and areas for improvement were recorded for states and I/DD websites.
      The researchers conclude that a number of additional health and support services
      will be needed to address the growing needs of this vulnerable population. 

PMID- 25949825
TI  - The Application of GeneXpert MTB/RIF for Smear-Negative TB Diagnosis as a Fee
      Paying Service at a South Asian General Hospital.
AB  - The GeneXpert MTB/RIF assay (Xpert) is a novel automated diagnostic tool for
      tuberculosis but its optimal placement in the healthcare system has not been
      determined. The objective of this study was to determine the possibility of
      additional case detection for pulmonary tuberculosis (PTB) by offering Xpert to
      smear-negative patients in a low-HIV burden setting with no Mycobacterium
      tuberculosis (M.tb.) culture facilities. Patients routinely presenting with
      symptoms suggestive of PTB with negative smears were offered single Xpert test on
      a fee-paying basis. Data were retrospectively reviewed to determine case
      detection in patients tested from February to December 2013. Symptoms associated
      with a positive test were analysed to determine if refinement of clinical
      criteria would reduce unnecessary testing. 258 smear-negative patients were
      included and M.tb. was detected in 55 (21.32%, n = 55/258). Using standard
      clinical assessment for selection, testing 5 patients detected one case of smear
      negative PTB. These results demonstrate that fee-paying Xpert service in low
      income setting can increase TB case confirmation substantially and further
      systematic studies of health economic implications should be conducted to
      determine optimal implementation models to increase access to Xpert in low- and
      middle-income countries. 

PMID- 25949826
TI  - Isolated T Wave Inversion in Lead aVL: An ECG Survey and a Case Report.
AB  - Background. Computerized electrocardiogram (ECG) analysis has been of tremendous
      help for noncardiologists, but can we rely on it? The importance of ST depression
      and T wave inversions in lead aVL has not been emphasized and not well recognized
      across all specialties. Objective. This study's goal was to analyze if there is a
      discrepancy of interpretation by physicians from different specialties and a
      computer-generated ECG reading in regard to a TWI in lead aVL. Methods. In this
      multidisciplinary prospective study, a single ECG with isolated TWI in lead aVL
      that was interpreted by the computer as normal was given to all participants to
      interpret in writing. The readings by all physicians were compared by level of
      education and by specialty to one another and to the computer interpretation.
      Results. A total of 191 physicians participated in the study. Of the 191
      physicians 48 (25.1%) identified and 143 (74.9%) did not identify the isolated
      TWI in lead aVL. Conclusion. Our study demonstrated that 74.9% did not recognize
      the abnormality. New and subtle ECG findings should be emphasized in their
      training so as not to miss significant findings that could cause morbidity and
      mortality. 

PMID- 25949828
TI  - Locoregional and Distant Recurrence Patterns in Young versus Elderly Women
      Treated for Breast Cancer.
AB  - Objective. This study examined recurrence patterns in breast cancer patients
      younger than age of 40 and older than age of 75, two groups that are
      underrepresented in clinical trials and not routinely screened by mammography.
      Methods. The records of 230 breast cancer patients (n = 125 less than 40 and n =
      105 greater than 75) who presented to the Emory University Department of
      Radiation Oncology for curative treatment between 1997 and 2010 were reviewed.
      Data recorded included disease presentation, treatment, and areas of locoregional
      recurrence. Results. Women less than 40 years of age had higher rates of
      locoregional recurrence (20% versus 7%, P = 0.004) and distant recurrence (18%
      versus 5%, P = 0.003) than patients above 75 years of age. On multivariate
      analysis, patient age less than 40 was the only significant predictor of
      locoregional recurrence (P = 0.018). In a univariate analysis of each age group,
      receptor status and postlumpectomy radiation were significant predictors of
      locoregional recurrence-free survival in younger women while mammography
      screening predicted for distant recurrence-free survival in older patients.
      Conclusion. The factors identified in our age-stratified analysis highlight
      patients who are at high risk of locoregional and distant recurrence. Future
      studies aimed at enhancing therapies in young patients are warranted. 

PMID- 25949823
TI  - Performance Enhancing Diets and the PRISE Protocol to Optimize Athletic
      Performance.
AB  - The training regimens of modern-day athletes have evolved from the sole emphasis
      on a single fitness component (e.g., endurance athlete or resistance/strength
      athlete) to an integrative, multimode approach encompassing all four of the major
      fitness components: resistance (R), interval sprints (I), stretching (S), and
      endurance (E) training. Athletes rarely, if ever, focus their training on only
      one mode of exercise but instead routinely engage in a multimode training
      program. In addition, timed-daily protein (P) intake has become a hallmark for
      all athletes. Recent studies, including from our laboratory, have validated the
      effectiveness of this multimode paradigm (RISE) and protein-feeding regimen,
      which we have collectively termed PRISE. Unfortunately, sports nutrition
      recommendations and guidelines have lagged behind the PRISE integrative nutrition
      and training model and therefore limit an athletes' ability to succeed. Thus, it
      is the purpose of this review to provide a clearly defined roadmap linking
      specific performance enhancing diets (PEDs) with each PRISE component to
      facilitate optimal nourishment and ultimately optimal athletic performance. 

PMID- 25949830
TI  - Double orifice mitral valve and bicuspid aortic valve: pieces of the same single
      puzzle?
AB  - Double orifice mitral valve is a very rare congenital abnormality. Well known
      associations of this pathology with other congenital lesions point to a complex
      and central pathophysiological mechanism leading to a sequence of pathologies.
      These associations have long been realized and arbitrarily defined as Shone
      complex. We would like to present a 21-year-old patient with double orifice
      mitral valve associated with bicuspid aortic valve, with a brief review of the
      literature on possible central mechanisms leading to different subsets of
      congenital abnormalities involving these two. 

PMID- 25949829
TI  - Anxious and nonanxious mice show similar hippocampal sensory evoked oscillations
      under urethane anesthesia: difference in the effect of buspirone.
AB  - Hippocampal oscillations recorded under urethane anesthesia are proposed to be
      modulated by anxiolytics. All classes of clinically effective anxiolytics were
      reported to decrease the frequency of urethane theta; however, recent findings
      raise concerns about the direct correlation of anxiolysis and the frequency of
      hippocampal theta. Here, we took advantage of our two inbred mouse strains
      displaying extremes of anxiety (anxious (AX) and nonanxious (nAX)) to compare the
      properties of hippocampal activity and to test the effect of an anxiolytic drugs.
      No difference was observed in the peak frequency or in the peak power between AX
      and nAX strains. Buspirone (Bus) applied in 2.5 mg/kg decreased anxiety of AX but
      did not have any effect on nAX as was tested by elevated plus maze and open
      field. Interestingly, Bus treatment increased hippocampal oscillatory frequency
      in the AX but left it unaltered in nAX mice. Saline injection did not have any
      effect on the oscillation. Paired-pulse facilitation was enhanced by Bus in the
      nAX, but not in the AX strain. Collectively, these results do not support the
      hypothesis that hippocampal activity under urethane may serve as a marker for
      potential anxiolytic drugs. Moreover, we could not confirm the decrease of
      frequency after anxiolytic treatment.

PMID- 25949831
TI  - Type 4 dual left anterior descending artery: a very rare coronary anomaly
      circulation.
AB  - Coronary artery anomalies are congenital changes in their origin, course, and/or
      structure. They are the second most frequent cause of sudden death in young
      athletes. Dual LAD artery is a rare coronary anomaly. We present the case of a 44
      year-old man with recent onset exertional angina and documented ischemia whose
      coronary angiogram and computed tomography (CT) showed type 4 dual LAD artery,
      the rarest and most interesting variant. 

PMID- 25949832
TI  - Comment on "nonsyndromic mandibular symphysis cleft".

PMID- 25949833
TI  - Immediate, early, and conventional implant placement in a patient with history of
      periodontitis.
AB  - The aim of this paper is to describe a case of implant-prosthetic rehabilitation
      in a patient with periodontitis, focusing on the different timing of implant
      placement. After initial periodontal treatment, teeth with advanced mobility
      degree and severe bone resorption were extracted. At different healing time oral
      implants were placed in a prosthetic-guided position. After osseointegration
      period the implants were loaded and the results at one year of follow-up are
      presented. 

PMID- 25949834
TI  - Optimal Molecular Methods in Detecting p190 (BCR-ABL) Fusion Variants in
      Hematologic Malignancies: A Case Report and Review of the Literature.
AB  - Patients with BCR-ABL1 positive hematologic malignancies and Philadelphia-like B
      lymphoblastic leukemia (B-ALL) are potential candidates for targeted therapy with
      tyrosine kinase inhibitors (TKI). Before TKIs, patients with B-ALL had a much
      worse prognosis and current treatments with targeted TKI therapy have improved
      outcomes. Thus, the detection of BCR-ABL1 is crucial and a false negative BCR
      ABL1 result may adversely affect patient care. We report a case of a 76-year-old
      male with a new diagnosis of B-ALL who was initially found to be BCR-ABL1
      negative by quantitative polymerase chain reaction (PCR). A concurrent
      qualitative PCR was performed which detected a positive BCR-ABL1 result that was
      confirmed by a next generation sequencing (NGS) based assay and identified as the
      rare fusion variant e1a3 of p190(BCR-ABL). Based on this result, the patient was
      placed on dasatinib as a targeted therapy. In the era of molecular diagnostic
      medicine and targeted therapy, it is essential to have an understanding of the
      limitations of molecular assays and to follow a comprehensive diagnostic approach
      in order to detect common abnormalities and rare variants. Incorporating NGS
      methods in an algorithmic manner into the standard diagnostic PCR-based approach
      for BCR-ABL1 will aid in minimizing false negative results. 

PMID- 25949835
TI  - Rare form of erdheim-chester disease presenting with isolated central skeletal
      lesions treated with a combination of alfa-interferon and zoledronic Acid.
AB  - Erdheim-Chester disease (ECD) represents a clonal non-Langerhans histiocytosis,
      which manifests under an extensive variety of clinical symptoms. This creates a
      challenge for the physician, who is required to recognize and diagnose the
      disease in the early stages. Despite this considerable challenge, in the last
      decade there has been a dramatic increase in ECD diagnoses, in most part due to
      an increasing awareness of this rare disorder. Involvement of the axial skeleton
      is exclusively uncommon with no official recommendations for the treatment of the
      bone lesions. Here, we present a case report of a young male patient with
      isolated lesions of the spine, ribs, and pelvis, who was successfully treated
      with a combination therapy of alfa-interferon and zoledronic acid. 

PMID- 25949836
TI  - Severe hyperammonemia in late-onset ornithine transcarbamylase deficiency
      triggered by steroid administration.
AB  - Ornithine transcarbamylase deficiency (OTCD) is a rare X-linked disorder of urea
      synthesis leading to hyperammonemia. Several late-onset cases have been reported.
      Undiagnosed and untreated patients are at the risk of death or suffering from
      irreversible sequelae. We describe a 56-year-old patient who presented with acute
      encephalopathy after steroid treatment. Hyperammonemia due to OTCD was diagnosed
      and a mutation was found. This allowed us to diagnose two other family members
      with unexplained encephalopathy who are now asymptomatic on a low-protein diet.
      OTCD should be considered in any patient with hyperammonemic encephalopathy and
      immediate treatment should be given to avoid a fatal outcome. We emphasize the
      need to examine other family members if the diagnosis is confirmed, in order to
      prevent further life-threatening episodes of encephalopathy or neonatal coma of
      newborn. 

PMID- 25949827
TI  - Emerging risk biomarkers in cardiovascular diseases and disorders.
AB  - Present review article highlights various cardiovascular risk prediction
      biomarkers by incorporating both traditional risk factors to be used as
      diagnostic markers and recent technologically generated diagnostic and
      therapeutic markers. This paper explains traditional biomarkers such as lipid
      profile, glucose, and hormone level and physiological biomarkers based on
      measurement of levels of important biomolecules such as serum ferritin,
      triglyceride to HDLp (high density lipoproteins) ratio, lipophorin-cholesterol
      ratio, lipid-lipophorin ratio, LDL cholesterol level, HDLp and apolipoprotein
      levels, lipophorins and LTPs ratio, sphingolipids, Omega-3 Index, and ST2 level.
      In addition, immunohistochemical, oxidative stress, inflammatory, anatomical,
      imaging, genetic, and therapeutic biomarkers have been explained in detail with
      their investigational specifications. Many of these biomarkers, alone or in
      combination, can play important role in prediction of risks, its types, and
      status of morbidity. As emerging risks are found to be affiliated with minor and
      microlevel factors and its diagnosis at an earlier stage could find CVD, hence,
      there is an urgent need of new more authentic, appropriate, and reliable
      diagnostic and therapeutic markers to confirm disease well in time to start the
      clinical aid to the patients. Present review aims to discuss new emerging
      biomarkers that could facilitate more authentic and fast diagnosis of CVDs, HF
      (heart failures), and various lipid abnormalities and disorders in the future. 

PMID- 25949838
TI  - Comment on "intrapartum intrauterine fetal demise with normal umbilical cord
      blood gas values at birth".

PMID- 25949837
TI  - Extraspinal type I dural arteriovenous fistula with a lumbosacral
      lipomyelomeningocele: a case report and review of the literature.
AB  - Seven cases of adult spinal vascular malformations presenting in conjunction with
      spinal dysraphism have been reported in the literature. Two of these involved
      male patients with a combined dural arteriovenous fistula (DAVF) and
      lipomyelomeningocele. The authors present the third case of a patient with an
      extraspinal DAVF and associated lipomyelomeningocele in a lumbosacral location. A
      58-year-old woman with rapid decline in bilateral motor function 10 years after a
      prior L4-5 laminectomy and cord detethering for diagnosed tethered cord underwent
      magnetic resonance imaging showing evidence of persistent cord tethering and a
      lipomyelomeningocele. Diagnostic spinal angiogram showed a DAVF with arterial
      feeders from bilateral sacral and the right internal iliac arteries. The patient
      underwent Onyx embolization of both feeding right and left lateral sacral
      arteries. At 6-month follow-up, MRI revealed decreased flow voids and new
      collateralized supply to the DAVF. The patient underwent successful
      lipomyelomeningocele exploration, resection, AV fistula ligation, and cord
      detethering. This report discusses management of this patient as well as the
      importance of endovascular embolization followed by microsurgery for the
      treatment of cases with combined vascular and dysraphic anomalies. 

PMID- 25949839
TI  - Giant vulvar epidermoid cyst in an adolescent girl.
AB  - Introduction. Vulvar cyst in adolescent girls is very uncommon. Epidermoid cyst
      can be seen in many sites including face, trunk, and extremities but its
      occurrence in vulva is uncommon. This is the first case of epidermoid cyst of
      vulva reported in an adolescent girl. Case. A 17-year-old, adolescent girl
      admitted to our gynecology outpatient clinic with a complaint of painful and
      palpable mass in her vulva. On examination, a giant mass located in left vulva
      and labia majora with 11 cm in diameter was seen. The magnetic resonance imaging
      (MRI) showed a well-defined cystic mass without contrast enhancement. The surgery
      was advised to the patient and the pathologic examination of mass revealed vulvar
      epidermoid cyst. Discussion. Vulvar cysts generally grow slowly and the main
      etiologies are vulvar trauma and surgical interventions including episiotomy and
      female circumcision in some culture. The exact treatment is total surgical
      excision and pathologic examination. MRI is an important imaging modality for
      detection of extension to deep perineal tissue and localization of mass in vulva
      especially in giant ones. Conclusion. Although vulvar mass in adolescents is
      rare, the epidermoid cyst with benign origin should be kept in mind. 

PMID- 25949840
TI  - Top-down computerized cognitive remediation in schizophrenia: a case study of an
      individual with impairment in verbal fluency.
AB  - The objective of this case study was to assess the specific effect of cognitive
      remediation for schizophrenia on the pattern of cognitive impairments. Case A is
      a 33-year-old man with a schizophrenia diagnosis and impairments in visual
      memory, inhibition, problem solving, and verbal fluency. He was provided with a
      therapist delivered cognitive remediation program involving practice and strategy
      which was designed to train attention, memory, executive functioning, visual
      perceptual processing, and metacognitive skills. Neuropsychological and clinical
      assessments were administered at baseline and after three months of treatment. At
      posttest assessment, Case A had improved significantly on targeted (visual memory
      and problem solving) and nontargeted (verbal fluency) cognitive processes. The
      results of the current case study suggest that (1) it is possible to improve
      specific cognitive processes with targeted exercises, as seen by the improvement
      in visual memory due to training exercises targeting this cognitive domain; (2)
      cognitive remediation can produce improvements in cognitive processes not
      targeted during remediation since verbal fluency was improved while there was no
      training exercise on this specific cognitive process; and (3) including learning
      strategies in cognitive remediation increases the value of the approach and
      enhances participant improvement, possibly because strategies using verbalization
      can lead to improvement in verbal fluency even if it was not practiced. 

PMID- 25949841
TI  - Granulomatosis with polyangiitis presenting as a choroidal tumor.
AB  - Granulomatosis with polyangiitis (GPA) sometimes involves the eye orbit; however,
      choroidal involvements in GPA had been rarely reported. We report a rare case
      presenting with a choroidal mass in an 83-year-old Japanese woman who presented
      with left eye pain. Diagnostic biopsy revealed necrotizing vasculitis with
      infiltrates of inflammatory cells. Diagnosis was localized granulomatosis with
      polyangiitis. Combined treatments with corticosteroid plus azathioprine resolved
      the choroidal mass region. Although treatment with corticosteroid and
      immunosuppressive agents improves the prognosis of the disease, ocular morbidity
      is still well recognized. Clinicians should consider a differential diagnosis of
      GPA in patients with inflammatory choroidal tumors. 

PMID- 25949842
TI  - Corrigendum to "high-dose subcutaneous immunoglobulins for the treatment of
      severe treatment-resistant polymyositis".
AB  - [This corrects the article DOI: 10.1155/2014/458231.]. 

PMID- 25949843
TI  - Diagnosis and Management of Perforated Duodenal Ulcers following Roux-En-Y
      Gastric Bypass: A Report of Two Cases and a Review of the Literature.
AB  - Perforated duodenal ulcers are rare complications seen after roux-en-Y gastric
      bypass (RYGP). They often present as a diagnostic dilemma as they rarely present
      with pneumoperitoneum on radiologic evaluation. There is no consensus as to the
      pathophysiology of these ulcers; however expeditious treatment is necessary. We
      present two patients with perforated duodenal ulcers and a distant history of
      RYGP who were successfully treated. Their individual surgical management is
      discussed as well as a literature review. We conclude that, in patients who
      present with acute abdominal pain and a history of RYGB, perforated ulcer needs
      to be very high in the differential diagnosis even in the absence of
      pneumoperitoneum. In these patients an early surgical exploration is paramount to
      help diagnose and treat these patients. 

PMID- 25949844
TI  - Symptomatic infundibulopelvic dysgenesis in an adolescent.
AB  - Infundibulopelvic dysgenesis is a rare condition characterized by congenital
      malformation of the pelvicalyceal system. We present the case of an 18-year-old
      boy with chronic intermittent right flank pain and cystic dilation with
      parenchymal thinning on ultrasonography. The left kidney was normal. The patient
      denied dysuria, constipation, and history of UTIs or renal calculi. Cystoscopy
      with retrograde pyelogram showed marked stenosis of the right pelvicalyceal
      system and anatomy unfavorable to stenting. The patient's symptoms were
      unresponsive to conservative management. Reconstruction of the right collecting
      system was unsuccessful and a simple nephrectomy was performed, which led to
      complete resolution of his symptoms. 

PMID- 25949845
TI  - Inflammatory bowel disease: Traditional knowledge holds the seeds for the future.
AB  - Despite the level of sophistication they have reached nowadays, the available
      tools for treatment of inflammatory bowel disease (IBD) can at best chronicize
      the disease but not cure it. Chances to make leap forward from this hold-back may
      include designs to reach personalized treatment strategies taking advantage of
      modern genome associated studies, and shift resources towards unfolding inciting
      pathogenetic steps rather than continuing to develop drugs that address down
      stream phenomena. We have arbitrarily chosen to scrutinize a few projects that
      may make their way in 2015 and mark the history of IBD research. The list
      includes: the role of appendix as a regulating factor in pathogenesis of
      ulcerative colitis/proctitis; the reappraisal of (auto)immune phenomena in the
      era of microbiome; projects to treat IBD by stem cell infusion; recognition of
      the crucial pathogenetic role of gut microbiome, and attempts to modify it to
      treat enteric diseases, from clostridium difficile infection to IBD. 

PMID- 25949846
TI  - Clinical relevance of clopidogrel-proton pump inhibitors interaction.
AB  - Clopidogrel is a widely used antiplatelet agent for the secondary prevention of
      cardiovascular events in patients with stable coronary heart disease, acute
      coronary syndromes and ischemic stroke. Even though clopidogrel is safer than
      aspirin in terms of risk for gastrointestinal (GI) bleeding, the elderly, and
      patients with a history of prior GI bleeding, with Helicobacter pylori infection
      or those who are also treated with aspirin, anticoagulants, corticosteroids or
      nonsteroidal anti-inflammatory drugs are at high risk for GI complications when
      treated with clopidogrel. Accordingly, proton pump inhibitors are frequently
      administered in combination with clopidogrel to reduce the risk for GI bleeding.
      Nevertheless, pharmacodynamic studies suggest that omeprazole might attenuate the
      antiplatelet effect of clopidogrel. However, in observational studies, this
      interaction does not appear to translate into increased cardiovascular risk in
      patients treated with this combination. Moreover, in the only randomized, double
      blind study that assessed the cardiovascular implications of combining
      clopidogrel and omeprazole, patients treated with clopidogrel/omeprazole
      combination had reduced risk for GI events and similar risk for cardiovascular
      events than patients treated with clopidogrel and placebo. However, the premature
      interruption of the study and the lack of power analysis in terms of the
      cardiovascular endpoint do not allow definite conclusions regarding the
      cardiovascular safety of clopidogrel/omeprazole combination. Other proton pump
      inhibitors do not appear to interact with clopidogrel. Nevertheless, given the
      limitations of existing observational and interventional studies, the decision to
      administer proton pump inhibitors to patients treated with clopidogrel should be
      individualized based on the patient's bleeding and cardiovascular risk. 

PMID- 25949847
TI  - Clinical relevance of intestinal peptide uptake.
AB  - AIM: To determine available information on an independent peptide transporter 1
      (PepT1) and its potential relevance to treatment, this evaluation was completed.
      METHODS: Fully published English language literature articles sourced through
      PubMed related to protein digestion and absorption, specifically human peptide
      and amino acid transport, were accessed and reviewed. Papers from 1970 to the
      present, with particular emphasis on the past decade, were examined. In addition,
      abstracted information translated to English in PubMed was also included.
      Finally, studies and reviews relevant to nutrient or drug uptake, particularly in
      human intestine were included for evaluation. This work represents a summary of
      all of these studies with particular reference to peptide transporter mediated
      assimilation of nutrients and pharmacologically active medications. RESULTS:
      Assimilation of dietary protein in humans involves gastric and pancreatic enzyme
      hydrolysis to luminal oligopeptides and free amino acids. During the ensuing
      intestinal phase, these hydrolytic products are transported into the epithelial
      cell and, eventually, the portal vein. A critical component of this process is
      the uptake of intact di-peptides and tri-peptides by an independent PepT1. A
      number of "peptide-mimetic" pharmaceutical agents may also be transported through
      this carrier, important for uptake of different antibiotics, antiviral agents and
      angiotensin-converting enzyme inhibitors. In addition, specific peptide products
      of intestinal bacteria may also be transported by PepT1, with initiation and
      persistence of an immune response including increased cytokine production and
      associated intestinal inflammatory changes. Interestingly, these inflammatory
      changes may also be attenuated with orally-administered anti-inflammatory
      tripeptides administered as site-specific nanoparticles and taken up by this
      PepT1 transport protein. CONCLUSION: Further evaluation of the role of this
      transporter in treatment of intestinal disorders, including inflammatory bowel
      disease is needed.

PMID- 25949848
TI  - Cavernous malformation of the optic chiasm: An uncommon location.
AB  - BACKGROUND: Cavernous malformations (CMs) of the optic chiasm are rare lesions
      often presenting with acute chiasmal syndrome or a progressive visual loss. The
      case of a 48-year-old female with an intrachiasmatic CM is presented. CASE
      DESCRIPTION: The patient presented with an insidious history of progressive
      visual loss. Magnetic resonance imaging (MRI) showed a CM in the suprasellar
      region. The patient was operated via a right pterional approach with a complete
      lesion removal. The postoperative course was uneventful. Early postoperative
      ophthalmological examination revealed minimal improvement of the vision in the
      left eye. CONCLUSION: The clinical, neuroradiological, and intraoperative
      findings are presented, along with a review of the literature.

PMID- 25949850
TI  - Endoscopic foraminotomy for recurrent lumbar radiculopathy after TLIF: Technical
      report.
AB  - BACKGROUND: Transforaminal lumbar interbody fusion (TLIF) is a well-accepted
      fusion technique that uses unilateral facet removal as an oblique corridor for
      inserting an interbody spacer. This manuscript focused on five cases of
      endoscopic foraminotomy for patients presenting with recurrent radiculopathy
      after TLIF procedures. METHODS: After Institutional Review Board approval, charts
      from five patients with lumbar radiculopathy and instrumented TLIF procedures who
      underwent subsequent endoscopic procedures between 2011 and 2013 were reviewed.
      RESULTS: The average pain relief 1 year postoperatively was reported to be 63.8%,
      good results as defined by MacNab. The average preoperative visual analog scale
      (VAS) score was 9.5, indicated in our questionnaire as severe and constant pain.
      The average 1 year postoperative VAS score was 3.5, indicated in our
      questionnaire as mild and intermittent pain. CONCLUSION: Transforaminal
      endoscopic discectomy and foraminotomy could be used as a safe, yet, minimally
      invasive and innovative technique for the treatment of lumbar radiculopathy in
      the setting of previous instrumented lumbar fusion. IRB APPROVAL: Lifespan: IRB
      Study # 600415.

PMID- 25949849
TI  - The role of metabolic therapy in treating glioblastoma multiforme.
AB  - Glioblastoma multiforme (GBM) is an aggressive and nearly uniformly fatal
      malignancy of the central nervous system. Despite extensive research and clinical
      trials over the past 50 years, very little progress has been made to
      significantly alter its lethal prognosis. The current standard of care (SOC)
      includes maximal surgical resection, radiation therapy and chemotherapy and
      temozolomide (TMZ), including the selective use of glucocorticoids for symptom
      control. These same treatments, however, have the potential to create an
      environment that may actually facilitate tumor growth and survival. Research
      investigating the unique metabolic needs of tumor cells has led to the proposal
      of a new metabolic treatment for various cancers including GBMs that may enhance
      the effectiveness of the SOC. The goal of metabolic cancer therapy is to restrict
      GBM cells of glucose, their main energy substrate. By recognizing the underlying
      energy production requirements of cancer cells, newly proposed metabolic therapy
      is being used as an adjunct to standard GBM therapies. This review will discuss
      the calorie restricted ketogenic diet (CR-KD) as a promising potential adjunctive
      metabolic therapy for patients with GBMs. The effectiveness of the CR-KD is based
      on the "Warburg Effect" of cancer metabolism and the microenvironment of GBM
      tumors. We will review recent case reports, clinical studies, review articles,
      and animal model research using the CR-KD and explain the principles of the
      Warburg Effect as it relates to CR-KD and GBMs. 

PMID- 25949852
TI  - Meningiomatosis restricted to the left cerebral hemisphere with acute clinical
      deterioration: Case presentation and discussion of treatment options.
AB  - BACKGROUND: True multiple meningiomas are defined as meningiomas occurring at
      several intracranial locations simultaneously without the presence of
      neurofibromatosis. Though the prognosis does not differ from benign solitary
      meningiomas, the simultaneous occurrence of different grades of malignancy has
      been reported in one-third of patients with multiple meningiomas. Due to its
      rarity, unclear etiology, and questions related to proper management, we are
      presenting our case of meningiomatosis and discuss possible pathophysiological
      mechanisms. CASE DESCRIPTION: We illustrate the case of a 55-year-old female with
      multiple meningothelial meningeomas exclusively located in the left cerebral
      hemisphere. The patient presented with acute vigilance decrement, aphasia, and
      vomiting. Further deterioration with sopor and nondirectional movements required
      oral intubation. Emergent magnetic resonance imaging (MRI) with MR-angiography
      disclosed a massive midline shift to the right due to widespread, plaque-like
      lesions suspicious for meningeomatosis, purely restricted to the left cerebral
      hemisphere. Emergency partial tumor resection was performed. Postoperative
      computed tomography (CT) scan showed markedly reduction of cerebral edema and
      midline shift. After tapering the sedation a right-sided hemiparesis resolved
      within 2 weeks, leaving the patient neurologically intact. CONCLUSION: Although
      multiple meningeomas are reported frequently, the presence of meningeomatosis
      purely restricted to one cerebral hemisphere is very rare. As with other
      accessible and symptomatic lesions, the treatment of choice is complete resection
      with clean margins to avoid local recurrence. In case of widespread distribution
      a step-by-step resection with the option of postoperative radiation of tumor
      remnants may be an option.

PMID- 25949851
TI  - Intracranial chordoma presenting as acute hemorrhage in a child: Case report and
      literature review.
AB  - BACKGROUND: Chordomas are rare, slow-growing malignant neoplasms derived from
      remnants of the embryological notochord. Pediatric cases comprise only 5% of all
      chordomas, but more than half of the reported pediatric chordomas are
      intracranial. For patients of all ages, intracranial chordomas typically present
      with symptoms such as headaches and progressive neurological deficits occurring
      over several weeks to many years as they compress or invade local structures.
      There are only reports of these tumors presenting acutely with intracranial
      hemorrhage in adult patients. CASE DESCRIPTION: A 10-year-old boy presented with
      acute onset of headache, emesis, and diplopia. Head computed tomography and
      magnetic resonance imaging of brain were suspicious for a hemorrhagic mass
      located in the left petroclival region, compressing the ventral pons. The mass
      was surgically resected and demonstrated acute intratumoral hemorrhage.
      Pathologic examination was consistent with chordoma. CONCLUSION: There are few
      previous reports of petroclival chordomas causing acute intracranial hemorrhage.
      To the authors' knowledge, this is the first case of a petroclival chordoma
      presenting as acute intracranial hemorrhage in a pediatric patient. Although
      uncommon, it is important to consider chordoma when evaluating a patient of any
      age presenting with a hemorrhagic lesion of the clivus.

PMID- 25949853
TI  - High risk of cerebrospinal fluid leakage in surgery of a rare primary
      intraosseous cavernous hemangioma of the clivus showing meningeal infiltration: A
      case report and review of the literature.
AB  - BACKGROUND: Primary intraosseous cavernous hemangiomas (PICH) of the skull
      represent an infrequent bone tumor. Although some rare cases of PICHs located in
      the skull base have been published, to our concern only three cases have been
      reported in the English literature of PICHs arising within the clivus. CASE
      DESCRIPTION: We present the case of a patient presenting an isolated abducens
      paresis due to a rare PICH of the clivus showing also an unusual destruction of
      the inner table as well as infiltration of the dura mater. Due to this uncommon
      infiltrative pattern of an otherwise expected intraosseous tumor, a cerebrospinal
      fluid (CSF)-fistula occurred while performing a transnasal biopsy. The patient
      recovered successfully without need of lumbar drainage or re-surgery.
      Additionally, intratumoral decompression was sufficient to relief the abducens
      paresis. CONCLUSIONS: Our case provides new and meaningful information about
      clinical features as well as growth pattern of these rare clival tumors. We also
      discuss the importance of knowing these peculiarities before surgery in order to
      plan the optimal operative management as well as to avoid complications while
      approaching PICHs localized in such a delicate cranial region.

PMID- 25949854
TI  - Retrograde cysto-myelogram: Case Report.
AB  - BACKGROUND: In the scenario of blunt trauma with suspected bladder injury,
      conventional retrograde cystography is the gold standard for accurate diagnosis.
      CASE DESCRIPTION: The authors report the case of a 54-year-old patient who
      presented with pelvic and sacral fractures and a ruptured bladder after being hit
      by a vehicle. A retrograde computed tomography cystogram demonstrated
      extraperitoneal extravasation of the contrast agent, which traversed violated
      sacral nerve roots, resulting in contrast entering the subarachnoid space at the
      left sacral ala predominantly through the left L5 and S1 nerve roots.
      CONCLUSIONS: This is the first known report of an accidental myelogram imaging
      performed through a retrograde cystogram.

PMID- 25949855
TI  - Intradural extramedullary capillary hemangioma of the cauda equina: Case report
      and literature review.
AB  - BACKGROUND: Capillary hemangiomas are benign vascular tumors that rarely occur in
      the neuraxis. When encountered in the spine, prompt diagnosis and complete
      resection is crucial. On rare instances, these lesions can acutely hemorrhage,
      leading to sudden neurological decline. To date, there are only 16 reported cases
      of intradural capillary hemangiomas in the cauda equina. CASE DESCRIPTION: We
      report a case of an intradural extramedullary cauda equina capillary hemangioma
      that resulted in back pain and lower extremity motor deficit. Initial magnetic
      resonance (MR) imaging demonstrated a bilobular intradural L3-4 cauda equina
      lesion. The lesion was isointense on T1-weighted imaging, mildly hyperintense on
      T2-weighted images and avidly enhancing after gadolinium administration.
      Pathology confirmed the diagnosis of capillary hemangioma. CONCLUSION: Early
      diagnosis and treatment of this patient resulted in complete resection of the
      tumor and return of lower extremity motor function. Capillary hemangiomas should
      be considered in the differential diagnosis of cauda equina lesions. En bloc
      resection of these lesions is the mainstay of treatment.

PMID- 25949856
TI  - Meningioma of the superior leaflet of the velum interpositum: A case report.
AB  - BACKGROUND: Meningiomas of the velum interpositum in the roof of the third
      ventricle are rare. Knowing from which leaflet the meningioma originates and thus
      its relationships with the internal cerebral and Galen veins, may help in
      choosing the surgical approach. CASE DESCRIPTION: We report the case of a 40-year
      old male with a meningioma arising from the superior leaflet of the velum
      interpositum. The tumor was resected successfully using the infratentorial
      supracerebellar approach. Reviewing the literature, of the 22 reported cases of
      velum interpositum meningiomas, sufficient information regarding the precise
      location of the origin of the tumor was provided in 14 cases, all of which were
      from the inferior leaflet. CONCLUSION: We report the first case of velum
      interpositum meningioma arising from the superior leaflet and give a potential
      explanation as to why meningiomas of the velum interpositum occur more commonly
      on the inferior leaflet. Distinguishing from which of the two leaflets the tumor
      originates may influence the surgical strategy.

PMID- 25949857
TI  - Activatable Dendritic 19F Probes for Enzyme Detection.
AB  - We describe a novel activatable probe for fluorine-19 NMR based on self
      assembling amphiphilic dendrons. The dendron probe has been designed to be
      spectroscopically silent due to the formation of large aggregates. Upon exposure
      to the specific target enzyme, the aggregates disassemble to give rise to a sharp
      19F NMR signal. The probe is capable of detecting enzyme concentrations in the
      low nanomolar range. Response time of the probe was found to be affected by the
      hydrophilic-lipophilic balance of dendrons. Understanding the structural factors
      that underlie this design principle provides the pathway for using this strategy
      for a broad range of enzyme-based imaging.

PMID- 25949859
TI  - Tumorigenic Th17 cells in oncogenic Kras-driven and inflammation-accelerated lung
      cancer.
AB  - Although inflammation has been linked to lung cancer pathogenesis, very little is
      known about the critical players during lung cancer development. We found that
      Kras mutation in lung epithelial cells preferentially leads to recruitment of
      Th17 cells, which produce IL-17, a signature cytokine that promotes inflammation.
      We demonstrated IL-17 is critical for tumor growth in part by recruiting
      tumorigenic GR1+ CD11b+ cells.

PMID- 25949858
TI  - Myeloid derived suppressor cells-An overview of combat strategies to increase
      immunotherapy efficacy.
AB  - Myeloid-derived suppressor cells (MDSCs) contribute to tumor-mediated immune
      escape and negatively correlate with overall survival of cancer patients.
      Nowadays, a variety of methods to target MDSCs are being investigated. Based on
      the intervention stage of MDSCs, namely development, expansion and activation,
      function and turnover, these methods can be divided into: (I) prevention or
      differentiation to mature cells, (II) blockade of MDSC expansion and activation,
      (III) inhibition of MDSC suppressive activity or (IV) depletion of intratumoral
      MDSCs. This review describes effective mono- or multimodal-therapies that target
      MDSCs for the benefit of cancer treatment.

PMID- 25949860
TI  - Distinct patterns of intratumoral immune cell infiltrates in patients with HPV
      associated compared to non-virally induced head and neck squamous cell carcinoma.
AB  - Human papillomavirus (HPV) infection is one of the most important etiologic
      causes of oropharyngeal head and neck squamous cell carcinoma (HNSCC). Patients
      with HPV-positive HNSCC were reported to have a better clinical outcome than
      patients with HPV-negative cancers. However, little is known about the possible
      causes of different clinical outcomes. In this study, we analyzed a detailed
      immune profile of tumor samples from HNSCC patients with respect to their HPV
      status. We analyzed the characteristics of immune cell infiltrates, including the
      frequency and distribution of antigen-presenting cells and naive, regulatory and
      effector T cells and the cytokine and chemokine levels in tumor tissue. There was
      a profound difference in the extent and characteristics of intratumoral immune
      cell infiltrates in HNSCC patients based on their HPV status. In contrast to HPV
      negative tumor tissues, HPV-positive tumor samples showed significantly higher
      numbers of infiltrating IFNgamma+ CD8+ T lymphocytes, IL-17+ CD8+ T lymphocytes,
      myeloid dendritic cells and proinflammatory chemokines. Furthermore, HPV-positive
      tumors had significantly lower expression of Cox-2 mRNA and higher expression of
      PD1 mRNA compared to HPV-negative tumors. The presence of a high level of
      intratumoral immune cell infiltrates might play a crucial role in the
      significantly better response of HPV-positive patients to standard therapy and
      their favorable clinical outcome. Furthermore, characterization of the HNSCC
      immune profile might be a valuable prognostic tool in addition to HPV status and
      might help identify novel targets for therapeutic strategies, including cancer
      immunotherapy.

PMID- 25949861
TI  - Tryptophan 2,3-dioxygenase (TDO)-reactive T cells differ in their functional
      characteristics in health and cancer.
AB  - Tryptophan-2,3-dioxygenase (TDO) physiologically regulates systemic tryptophan
      levels in the liver. However, numerous studies have linked cancer with activation
      of local and systemic tryptophan metabolism. Indeed, similar to other heme
      dioxygenases TDO is constitutively expressed in many cancers. In the present
      study, we detected the presence of both CD8+ and CD4+ T-cell reactivity toward
      TDO in peripheral blood of patients with malignant melanoma (MM) or breast cancer
      (BC) as well as healthy subjects. However, TDO-reactive CD4+ T cells constituted
      distinct functional phenotypes in health and disease. In healthy subjects these
      cells predominately comprised interferon (IFN)gamma and tumor necrosis factor
      (TNF)-alpha producing Th1 cells, while in cancer patients TDO-reactive CD4+ T
      cells were more differentiated with release of not only IFNgamma and TNFalpha,
      but also interleukin (IL)-17 and IL-10 in response to TDO-derived MHC-class II
      restricted peptides. Hence, in healthy donors (HD) a Th1 helper response was
      predominant, whereas in cancer patients CD4+ T-cell responses were skewed toward
      a regulatory T cell (Treg) response. Furthermore, MM patients hosting a TDO
      specific IL-17 response showed a trend toward an improved overall survival (OS)
      compared to MM patients with IL-10 producing, TDO-reactive CD4+ T cells. For
      further characterization, we isolated and expanded both CD8+ and CD4+ TDO
      reactive T cells in vitro. TDO-reactive CD8+ T cells were able to kill HLA
      matched tumor cells of different origin. Interestingly, the processed and
      presented TDO-derived epitopes varied between different cancer cells. With
      respect to CD4+ TDO-reactive T cells, in vitro expanded T-cell cultures comprised
      a Th1 and/or a Treg phenotype. In summary, our data demonstrate that the immune
      modulating enzyme TDO is a target for CD8+ and CD4+ T cell responses both in
      healthy subjects as well as patients with cancer; notably, however, the
      functional phenotype of these T-cell responses differ depending on the respective
      conditions of the host.

PMID- 25949863
TI  - Impact of multiplicity of functional KIR-HLA compound genotypes on hepatocellular
      carcinoma.
AB  - Natural killer (NK) cells are potential immune components against hepatocellular
      carcinoma (HCC) after curative hepatectomy. Patients at high risk of HCC
      recurrence can be identified by quantifying NK cell licensing. Therefore,
      therapeutic strategies that manipulate NK cell activity may possibly improve the
      prognosis of HCC patients.

PMID- 25949864
TI  - Indoleamine 2,3-dioxygenase vaccination.
AB  - Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme. Remarkably, we
      discovered IDO-specific T cells that can influence adaptive immune reactions in
      patients with cancer. Further, a recent phase I clinical trial demonstrated long
      lasting disease stabilization without toxicity in patients with non-small-cell
      lung cancer (NSCLC) who were vaccinated with an IDO-derived HLA-A2-restricted
      epitope.

PMID- 25949862
TI  - Identification and characterization of the specific murine NK cell subset
      supporting graft-versus-leukemia- and reducing graft-versus-host-effects.
AB  - Clinical studies investigating the impact of natural killer (NK) cells in
      allogeneic hematopoietic stem cell transplantation settings have yielded
      promising results. However, NK cells are a functionally and phenotypically
      heterogeneous population. Therefore, we addressed the functional relevance of
      specific NK cell subsets distinguished by expression of CD117, CD27 and CD11b
      surface markers in graft-versus-leukemia (GVL)-reaction and graft-versus-host
      disease (GVHD). Our results clearly demonstrate that the subset of c-Kit-CD27
      CD11b+ NK cells expressed multiple cytotoxic pathway genes and provided optimal
      graft-versus-leukemia-effects, while significantly reducing T cell proliferation
      induced by allogeneic dendritic cells. Furthermore, these NK cells migrated to
      inflamed intestinal tissues where graft-versus-host-colitis was efficiently
      mitigated. For the first time, we identified the c-Kit-CD27-CD11b+ NK cell
      population as the specific effector NK cell subset capable of significantly
      diminishing GVHD in fully mismatched bone marrow transplantation settings. In
      conclusion, the subset of c-Kit-CD27-CD11b+ NK cells not only supports GVL, but
      also plays a unique role in the protection against GVHD by migrating to the
      peripheral GVHD target organs where they exert efficient immunoregulatory
      activities. These new insights demonstrate the importance of selecting the
      optimal NK cell subset for cellular immunotherapy following allogeneic
      hematopoietic stem cell transplantation.

PMID- 25949865
TI  - Immunotherapeutic intervention with oncolytic adenovirus in mouse mammary tumors.
AB  - The goal is to elucidate the immune modulating activity of an adenovirus (Adv)
      vector which showed therapeutic activity in human clinical trials. The oncolytic
      adenovirus (Adv/CD-TK) expressing two suicide genes was tested in two HER2/neu
      positive BALB/c mouse mammary tumor systems: rat neu-induced TUBO and human HER2
      transfected D2F2/E2. Intra-tumoral (i.t.) Adv/CD-TK injection of TUBO tumor plus
      systemic prodrug therapy showed limited antitumor activity, not exceeding that by
      the virus itself. Antibody (Ab) to the virus was induced in Adv-/Luc-treated
      mice, to coincide with the loss of transgene expression. Low replication activity
      of adenoviruses in rodent cells may limit viral persistence. Host immunity
      against Adv or Adv-infected cells further mutes suicide gene activity. Treatment
      of TUBO tumors with Adv/CD-TK alone, however, induced neu-specific Ab responses.
      Treatment with Adv/CD-TK/GM (Adv/GM) that also expressed mouse granulocyte
      macrophage colony stimulating factor (GM-CSF), but without prodrug treatment,
      delayed tumor growth, enhanced anti-neu Ab production and conferred complete
      protection against secondary tumor challenge. D2F2/E2 tumor-bearing mice showed
      decreased tumor growth following i.t. Adv/GM treatment and they generated greater
      HER2-specific T-cell responses. These data suggest that i.t. injection of Adv
      itself induces immune reactivity to tumor-associated antigens and the encoded
      cytokine, GM-CSF, amplifies that immune response, resulting in tumor growth
      inhibition. Incorporation of suicide gene therapy did not improve the efficacy of
      Adv therapy in this mouse mammary tumor system. Oncolytic adenoviral therapy may
      be streamlined and improved by substituting the suicide genes with immune
      modulating genes to exploit tumor immunity for therapeutic benefit.

PMID- 25949866
TI  - Angels and demons: Th17 cells represent a beneficial response, while neutrophil
      IL-17 is associated with poor prognosis in squamous cervical cancer.
AB  - The role of interleukin (IL)-17 in cancer remains controversial. In view of the
      growing interest in the targeting of IL-17, knowing its cellular sources and
      clinical implications is crucial. In the present study, we unraveled the
      phenotype of IL-17 expressing cells in cervical cancer using immunohistochemical
      double and immunofluorescent triple stainings. In the tumor stroma, IL-17 was
      found to be predominantly expressed by neutrophils (66%), mast cells (23%), and
      innate lymphoid cells (8%). Remarkably, T-helper 17 (Th17) cells were a minor IL
      17 expressing population (4%). A similar distribution was observed in the tumor
      epithelium. The Th17 and granulocyte fractions were confirmed in head and neck,
      ovarian, endometrial, prostate, breast, lung, and colon carcinoma. An above
      median number of total IL-17 expressing cells was an independent prognostic
      factor for poor disease-specific survival in early stage disease (p = 0.016).
      While a high number of neutrophils showed at trend toward poor survival, the
      lowest quartile of mast cells correlated with poor survival (p = 0.011). IL-17
      expressing cells and neutrophils were also correlated with the absence of vaso
      invasion (p < 0.01). IL-17 was found to increase cell growth or tightness of
      cervical cancer cell lines, which may be a mechanism for tumorigenesis in early
      stage disease. These data suggest that IL-17, primarily expressed by neutrophils,
      predominantly promotes tumor growth, correlated with poor prognosis in early
      stage disease. Strikingly, a high number of Th17 cells was an independent
      prognostic factor for improved survival (p = 0.026), suggesting Th17 cells are
      part of a tumor suppressing immune response.

PMID- 25949868
TI  - Immune signature of tumor infiltrating immune cells in renal cancer.
AB  - Tumor-associated immune cells have been discussed as an essential factor for the
      prediction of the outcome of tumor patients. Lymphocyte-specific genes are
      associated with a favorable prognosis in colorectal cancer but with poor survival
      in renal cell carcinoma (RCC). Flow cytometric analyses combined with
      immunohistochemistry were performed to study the phenotypic profiles of tumor
      infiltrating lymphocytes (TIL) and the frequency of T cells and macrophages in
      RCC lesions. Data were correlated with clinicopathological parameters and
      survival of patients. Comparing oncocytoma and clear cell (cc)RCC, T cell numbers
      as well as activation-associated T cell markers were higher in ccRCC, whereas the
      frequency of NK cells was higher in oncocytoma. An intratumoral increase of T
      cell numbers was found with higher tumor grades (G1:G2:G3/4 = 1:3:4). Tumor
      associated macrophages slightly increased with dedifferentiation, although the
      macrophage-to-T cell ratio was highest in G1 tumor lesions. A high expression of
      CD57 was found in T cells of early tumor grades, whereas T cells in
      dedifferentiated RCC lesions expressed higher levels of CD69 and CTLA4. TIL
      composition did not differ between older (>70 y) and younger (<58 y) patients.
      Enhanced patients' survival was associated with a higher percentage of tumor
      infiltrating NK cells and Th1 markers, e.g. HLA-DR+ and CXCR3+ T cells, whereas a
      high number of T cells, especially with high CD69 expression correlated with a
      worse prognosis of patients. Our results suggest that immunomonitoring of RCC
      patients might represent a useful tool for the prediction of the outcome of RCC
      patients.

PMID- 25949810
TI  - Design and methodology of SNAP-1: a Sprint National Anaesthesia Project to
      measure patient reported outcome after anaesthesia.
AB  - BACKGROUND: Patient satisfaction is an important metric of health-care quality.
      Accidental awareness under general anaesthesia (AAGA) is a serious complication
      of anaesthesia care which may go unrecognised in the immediate perioperative
      period but leads to long-term psychological harm for affected patients. The SNAP
      1 study aimed to measure patient satisfaction with anaesthesia care and the
      incidence of AAGA, reported on direct questioning within 24 h of surgery, in a
      large multicentre cohort. A secondary aim of SNAP-1 was to test the effectiveness
      of a new network of Quality Audit and Research Coordinators in NHS anaesthetic
      departments, to achieve widespread study participation and high patient
      recruitment rates. This manuscript describes the study methodology. METHODS: SNAP
      1 was a prospective observational cohort study. The study protocol was approved
      by the National Research Ethics Service. All UK NHS hospitals with anaesthetic
      departments were invited to participate. Adult patients undergoing any type of
      non-obstetric surgery were recruited in participating hospitals on 13th and 14th
      May 2014. Demographic data were collected by anaesthetists providing
      perioperative care. Patients were then approached within 24 h of surgery to
      complete two questionnaires-the Bauer patient satisfaction questionnaire (to
      measure patient reported outcome) and the modified Brice questionnaire (to detect
      possible accidental awareness). Completion of postoperative questionnaires was
      taken as evidence of implied consent. Results were recorded on a standard patient
      case report form, and local investigators entered anonymised data into an
      electronic database for later analysis by the core research team. RESULTS:
      Preliminary analyses indicate that over 15,000 patients were recruited across the
      UK, making SNAP-1 the largest NIHR portfolio-adopted study in anaesthesia to
      date. Both descriptive and analytic epidemiological analyses will be used to
      answer specific questions about the patient perception of anaesthesia care
      overall and in surgical sub-specialties and to determine the incidence of AAGA.
      CONCLUSIONS: The SNAP-1 study recruited a large number of UK hospitals and
      thousands of perioperative patients using newly established networks in the UK
      anaesthetic profession. The results will provide benchmarking information to aid
      interpretation of patient satisfaction data and also determine the incidence of
      AAGA reported on a single postoperative visit.

PMID- 25949867
TI  - Dab2, a negative regulator of DC immunogenicity, is an attractive molecular
      target for DC-based immunotherapy.
AB  - Dab2 is an adapter protein involved in receptor-mediated signaling, endocytosis,
      cell adhesion, hematopoietic cell differentiation, and angiogenesis. It plays a
      pivotal role in controlling cellular homeostasis. In the immune system, the Dab2
      is a Foxp3 target gene and is required for regulatory T (Treg) cell function.
      Dab2 expression and its biological function in dendritic cells (DCs) have not
      been described. In this study, we found that Dab2 was significantly induced
      during the development of mouse bone marrow (BM)-derived DCs (BMDCs) and human
      monocyte-derived DCs (MoDCs). Even in a steady state, Dab2 was expressed in mouse
      splenic DCs (spDCs). STAT5 activation, Foxp3 expression, and hnRNPE1 activation
      mediated by PI3K/Akt signaling were required for Dab2 expression during GM-CSF
      derived BMDC development regardless of TGF-beta signaling. Dab2-silencing was
      accompanied by enhanced IL-12 and IL-6 expression, and an improved capacity of DC
      for antigen uptake, migration and T cell stimulation, which generated strong CTL
      in vaccinated mice. Vaccination with Dab2-silenced DCs inhibited tumor growth
      more effectively than did vaccination with wild type DCs. Dab2-overexpression
      abrogated the efficacy of the DC vaccine in DC-based tumor immunotherapy. These
      data strongly suggest that Dab2 might be an intrinsic negative regulator of the
      immunogenicity of DCs, thus might be an attractive molecular target to improve DC
      vaccine efficacy.

PMID- 25949869
TI  - MHC-I modulation due to changes in tumor cell metabolism regulates tumor
      sensitivity to CTL and NK cells.
AB  - Tumor cells have a tendency to use glucose fermentation to obtain energy instead
      of mitochondrial oxidative phosphorylation (OXPHOS). We demonstrated that this
      phenotype correlated with loss of ERK5 expression and with reduced MHC class I
      expression. Consequently, tumor cells could evade cytotoxic T lymphocyte (CTL)
      mediated immune surveillance, but also increase their sensitivity to natural
      killer (NK) cells. These outcomes were evaluated using two cellular models:
      leukemic EL4 cells and L929 transformed fibroblasts and their derived rho degrees
      cell lines, which lack mitochondrial DNA. We have also used a L929 cell sub-line
      that spontaneously lost matrix attachment (L929dt), reminiscent of metastasis
      generation, that also downregulated MHC-I and ERK5 expression. MHC-I expression
      is lower in rho degrees  cells than in the parental cell lines, but they were
      equally sensitive to CTL. On the contrary, rho degrees  cells were more sensitive
      to activated NK cells than parental cells. On the other hand, L929dt cells were
      resistant to CTL and NK cells, showed reduced viability when forced to perform
      OXPHOS, and surviving cells increased MHC-I expression and became sensitive to
      CTL. The present results suggest that when the reduction in MHC-I levels in tumor
      cells due to glycolytic metabolism is partial, the increase in sensitivity to NK
      cells seems to predominate. However, when tumor cells completely lose MHC-I
      expression, the combination of treatments that increase OXPHOS with CTL-mediated
      immunotherapy could be a promising therapeutic approach.

PMID- 25949871
TI  - Anti-oxidant capacity and anti-tumor T cell function: A direct correlation.
AB  - Improving persistence and sustained function of effector CD8+ T cell response is
      key for achieving significant tumor control in adoptive T cell immunotherapy
      protocols. Our recent report shows that high anti-oxidant property is central to
      potent anti-tumor effector T cells, and directly correlates to CD62Lhi central
      memory, low glycolytic and low mitochondrial membrane potential phenotype, all of
      which may be linked and contribute to better tumor control.

PMID- 25949873
TI  - Reduced NADPH oxidase type 2 activity mediates sleep fragmentation-induced
      effects on TC1 tumors in mice.
AB  - The molecular mechanisms underlying how sleep fragmentation (SF) influences
      cancer growth and progression remain largely elusive. Here, we present evidence
      that SF reduced ROS production by downregulating gp91phox expression and activity
      in TC1 cell tumor associated macrophages (TAMs), while genetic ablation of
      phagocytic Nox2 activity increased tumor cell proliferation, motility, invasion,
      and extravasation in vitro. Importantly, the in vivo studies using
      immunocompetent syngeneic murine tumor models suggested that Nox2 deficiency
      mimics SF-induced TAMs infiltration and subsequent tumor growth and invasion.
      Taken together, these studies reveal that perturbed sleep could adversely affect
      innate immunity within the tumor by altering Nox2 expression and activity, and
      indicate that selective potentiation of Nox2 activity may present a novel
      therapeutic strategy in the treatment of cancer.

PMID- 25949872
TI  - IFNgamma producing CD8+ T cells modified to resist major immune checkpoints
      induce regression of MHC class I-deficient melanomas.
AB  - Tumors with reduced expression of MHC class I (MHC-I) molecules may be
      unrecognized by tumor antigen-specific CD8+ T cells and thus constitute a
      challenge for cancer immunotherapy. Here we monitored development of
      autochthonous melanomas in TiRP mice that develop tumors expressing a known tumor
      antigen as well as a red fluorescent protein (RFP) reporter knock in gene. The
      latter permits non-invasive monitoring of tumor growth by biofluorescence. One
      developing melanoma was deficient in cell surface expression of MHC-I, but MHC-I
      expression could be rescued by exposure of these cells to IFNgamma. We show that
      CD8+ T cells specific for tumor antigen/MHC-I were efficient at inducing
      regression of the MHC-I-deficient melanoma, provided that the T cells were
      endowed with properties permitting their migration into the tumor and their
      efficient production of IFNgamma. This was the case for CD8+ T cells transfected
      to express an active form of STAT5 (STAT5CA). The amount of IFNgamma produced ex
      vivo from T cells present in tumors after adoptive transfer of the CD8+ T cells
      was correlated with an increase in surface expression of MHC-I molecules by the
      tumor cells. We also show that these CD8+ T cells expressed PD-1 and upregulated
      its ligand PDL-1 on melanoma cells within the tumor. Despite upregulation of this
      immunosuppressive pathway, efficient IFNgamma production in the melanoma
      microenvironment was found associated with resistance of STAT5CA-expressing CD8+
      T cells to inhibition both by PD-1/PDL-1 engagement and by TGFbeta1, two main
      immune regulatory mechanisms hampering the efficiency of immunotherapy in
      patients.

PMID- 25949874
TI  - c-Met is a novel tumor associated antigen for T-cell based immunotherapy against
      NK/T cell lymphoma.
AB  - Background: The expression of c-Met and its ligand HGF plays a critical role in
      cell proliferation and is involved in numerous malignancies. Because c-Met
      expression and its role in NK/T-cell lymphoma remain unclear, we studied the
      expression and function of c-Met in NK/T-cell lymphoma cells. In addition, we
      investigated the possibility that c-Met could function as a tumor-associated
      antigen for helper T lymphocytes (HTLs). Methods: We evaluated whether HGF and c
      Met were expressed in NK/T-cell lymphoma and the capacity of predicted c-Met HTL
      epitopes to induce antitumor responses in vitro. In addition, c-Met inhibitor was
      evaluated for the ability to inhibit TGF-beta production in tumor and
      subsequently increase HTL recognition. Results: c-Met and HGF were expressed in
      NK/T-cell lymphoma cell lines, nasal NK/T-cell lymphoma specimens and patient
      serum samples. Moreover, HGF was shown to promote NK/T cell lymphoma (NKTCL)
      proliferation in an autocrine manner. Furthermore, we have identified three novel
      c-Met HTL epitopes that were restricted by several HLA-DR molecules. Notably,
      peptide-induced HTL lines directly recognized and killed c-Met expressing NK/T
      cell lymphomas and various epithelial solid tumors. The c-Met specific HTLs could
      also recognize dendritic cells (DCs) pulsed with c-Met expressing tumor cell
      lysates. In addition, we observed that c-Met inhibition augmented HTL recognition
      by decreasing TGF-beta production by tumor cells. Lastly, autophagy partly
      regulated the HTL responses against tumors. Conclusions: We identified novel c
      Met HTL epitopes that can elicit effective antitumor responses against tumors
      expressing c-Met. Our results provide the rationale of combining c-Met targeting
      therapy and immunotherapy for NKTCLs and epithelial tumors.

PMID- 25949875
TI  - Phase I trial of adoptively transferred tumor-infiltrating lymphocyte
      immunotherapy following concurrent chemoradiotherapy in patients with
      locoregionally advanced nasopharyngeal carcinoma.
AB  - Adoptive cell therapy (ACT) for cancers using autologous tumor-infiltrating
      lymphocytes (TILs) can induce immune responses and antitumor activity in
      metastatic melanoma patients. Here, we aimed to assess the safety and antitumor
      activity of ACT using expanded TILs following concurrent chemoradiotherapy (CCRT)
      in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Twenty
      three newly diagnosed, locoregionally advanced NPC patients were enrolled, of
      whom 20 received a single-dose of TIL infusion following CCRT. All treated
      patients were assessed for toxicity, survival and clinical and immunologic
      responses. Correlations between immunological responses and treatment
      effectiveness were further studied. Only mild adverse events (AEs), including
      Grade 3 neutropenia (1/23, 5%) consistent with immune-related causes, were
      observed. Nineteen of 20 patients exhibited an objective antitumor response, and
      18 patients displayed disease-free survival longer than 12 mo after ACT. A
      measurable plasma Epstein-Barr virus (EBV) load was detected in 14 patients at
      diagnosis, but a measurable EBV load was not found in patients after one week of
      ACT, and the plasma EBV load remained undetectable in 17 patients at 6 mo after
      ACT. Expansion and persistence of T cells specific for EBV antigens in peripheral
      blood following TIL therapy were observed in 13 patients. The apparent positive
      correlation between tumor regression and the expansion of T cells specific for
      EBV was further investigated in four patients. This study shows that NPC patients
      can tolerate ACT with TILs following CCRT and that this treatment results in
      sustained antitumor activity and anti-EBV immune responses. A larger phase II
      trial is in progress.

PMID- 25949870
TI  - Trial watch: Tumor-targeting monoclonal antibodies for oncological indications.
AB  - An expanding panel of monoclonal antibodies (mAbs) that specifically target
      malignant cells or intercept trophic factors delivered by the tumor stroma is now
      available for cancer therapy. These mAbs can exert direct
      antiproliferative/cytotoxic effects as they inhibit pro-survival signal
      transduction cascades or activate lethal receptors at the plasma membrane of
      cancer cells, they can opsonize neoplastic cells to initiate a tumor-targeting
      immune response, or they can be harnessed to specifically deliver toxins or
      radionuclides to transformed cells. As an indication of the success of this
      immunotherapeutic paradigm, international regulatory agencies approve new tumor
      targeting mAbs for use in cancer patients every year. Moreover, the list of
      indications for previously licensed molecules is frequently expanded to other
      neoplastic disorders as the results of large, randomized clinical trials become
      available. Here, we discuss recent advances in the preclinical and clinical
      development of tumor-targeting mAbs for oncological indications.

PMID- 25949876
TI  - A novel subset of B7-H3+CD14+HLA-DR-/low myeloid-derived suppressor cells are
      associated with progression of human NSCLC.
AB  - Myeloid-derived suppressor cells (MDSC) potently inhibit antitumor immune
      responses, and thereby promoti tumor progression and metastasis. However, the
      nature of human tumor-infiltrating MDSC remains poorly characterized. Here, we
      find B7-H3 is exclusively expressed on a subset of intratumoral CD14+HLA-DR-/low
      MDSC but absent from adjacent normal lung tissues of patients with non-small cell
      lung carcinoma (NSCLC). Cytokine analysis revealed that B7-H3+CD14+HLA-DR-/low
      MDSC (B7-H3+MDSC) produced higher levels of IL-10 and TNFalpha but lower levels
      of IL-1beta and IL-6 when compared with B7-H3-CD14+HLA-DR-/low myeloid-derived
      suppressor cells (B7-H3-MDSC). In a murine lung cancer model, B7-H3+MDSCs were
      found only in the tumor microenvironment and their frequencies increased during
      tumor progression. Clinical data analysis indicated that a higher frequency of B7
      H3+MDSCs was associated with reduced recurrence-free survival in patients with
      NSCLC. Taken together, we identify a novel subset of MDSCs within the tumor
      microenvironment that fosters tumor progression.

PMID- 25949877
TI  - Tumor stroma and chemokines control T-cell migration into melanoma following
      Temozolomide treatment.
AB  - The infiltration of T lymphocytes within tumors is associated with better
      outcomes in cancer patients, yet current understanding of factors that influence
      T-lymphocyte infiltration into tumors remains incomplete. In our study,
      Temozolomide (TMZ), a chemotherapeutic drug used to treat metastatic melanoma,
      induced T-cell infiltration into transplanted melanoma and into genitourinary
      (GU) tumors in mice developing spontaneous melanoma. In contrast, TMZ treatment
      did not increase T-cell infiltration into cutaneous tumors, despite similar
      increases in the expression of the (C-X-C) chemokines CXCL9 and CXCL10 in all
      sites after TMZ exposure. Our findings reveal that the matrix architecture of the
      GU tumor stroma, and its ability to present CXCL9 and CXCL10 after TMZ treatment
      played a key role in favouring T-cell infiltration. We subsequently demonstrate
      that modifications of these key elements by combined collagenase and TMZ
      treatment induced T-cell infiltration into skin tumors. T cells accumulating
      within GU tumors after TMZ treatment exhibited T helper type-1 effector and
      cytolytic functional phenotypes, which are important for control of tumor growth.
      Our findings highlight the importance of the interaction between tumor stroma and
      chemokines in influencing T-cell migration into tumors, thereby impacting immune
      control of tumor growth. This knowledge will aid the development of strategies to
      promote T-cell infiltration into cancerous lesions and has the potential to
      markedly improve treatment outcomes.

PMID- 25949878
TI  - PEITC treatment suppresses myeloid derived tumor suppressor cells to inhibit
      breast tumor growth.
AB  - Breast tumors are heterogeneous with a complex etiology. The immune system plays
      a crucial role in the development of tumors and can facilitate tumor growth
      pleiotropically. Myeloid derived suppressor cells (MDSCs) generate reactive
      oxygen species (ROS) and cytokines to suppress T cells, dendritic cells and
      natural killer (NK) cells. Hence, the inhibition of MDSCs could be an important
      strategy for anticancer therapeutics. Phenethyl isothiocyanate (PEITC), a
      bioactive compound present in cruciferous vegetables, is known to have anticancer
      properties. However, the effects of PEITC administration on the immune system
      have not been previously reported. In the current study, we evaluated the effects
      of administering PEITC to immunocompromised NOD-SCID IL2Rgamma-/- (SCID/NSG) host
      mice bearing MDA-MB-231 xenografts on MDSCs in the peripheral blood. Our results
      reveal that oral administration of 12 MUmol PEITC attenuated tumor growth by 76%.
      This was marked tumor-inhibitory phenotype was associated with a significant
      reduction in the levels of MDSCs bearing the surface markers CD33, CD34 and CD11b
      in PEITC treated mice, indicating that overall tumor growth suppression by PEITC
      correlates with inhibition of MDSCs. To the best of our knowledge, this is the
      first study showing effects of PEITC on MDSCs.

PMID- 25949879
TI  - Indoleamine-2,3-dioxygenase (IDO) metabolic activity is detrimental for cervical
      cancer patient survival.
AB  - The expression of the immunomodulating enzyme indoleamine-2,3-dioxygenase (IDO)
      suppresses T-lymphocyte function, thus correlating with poor survival in a
      variety of cancer patients. IDO degrades the essential amino acid tryptophan
      leading to immunosuppressive kynurenines production. In the present study,
      concentrations of tryptophan, 3-hydroxykynurenine, and kynurenine were measured
      in pre-treatment serum samples of 251 cervical cancer patients by a mass
      spectrometric method (XLC-MS/MS) and IDO activity determined by the
      kynurenine/tryptophan (Kyn/Trp) ratio. A low concentration of tryptophan was
      found to be significantly associated with tumors greater than 4 cm and lymph node
      metastatic spread. Furthermore, significant positive correlations were found
      between high concentrations of the tryptophan metabolites kynurenine and 3
      hydroxykynurenine and advanced disease stage (FIGO >IIA) and lymph node
      metastases. High levels of kynurenine were further associated with parametrial
      invasion and tumor size. A high Kyn/Trp ratio was related to lymph node
      metastasis, FIGO stage, tumor size, parametrial invasion and poor disease
      specific survival. These results suggest that IDO activation is linked to poor
      clinicopathological parameters and worse survival in cervical cancer, warranting
      the use of IDO inhibitors in future clinical trials.

PMID- 25949880
TI  - Discordant humoral and cellular immune responses to Cytomegalovirus (CMV) in
      glioblastoma patients whose tumors are positive for CMV.
AB  - Background. Glioblastoma (GBM) is the most common malignant brain tumor in adults
      and is nearly always fatal. Emerging evidence suggests that human Cytomegalovirus
      (HCMV) is present in 90-100% of GBMs and that add-on antiviral treatment for HCMV
      show promise to improve survival. Methods. In a randomized, placebo-controlled
      trial of valganciclovir in 42 GBM patients, blood samples were collected for
      analyses of HCMV DNA, RNA, reactivity against HCMV peptides, IgG, and IgM at
      baseline and at 3, 12, and 24 weeks of treatment. Results. All 42 tumors were
      positive for HCMV protein. All patients examined had at least one blood sample
      positive for HCMV DNA, 63% were HCMV RNA positive, and 21% were IgM positive.
      However, 29% of GBM patients were IgG negative for HCMV. Five of these samples
      were positive in an enzyme-linked immunosorbent assay (ELISA) that used antigens
      derived from a clinical isolate. Blood T cells from 11 of 13 (85%) HCMV IgG
      negative GBM patients reacted against HCMV peptides. Valganciclovir did not
      affect IgG titers, DNA, or RNA levels of the HCMV immediate early (HCMV IE) gene
      in blood. Conclusion. In GBM patients, HCMV activity is higher than in healthy
      controls and serology is a poor test to define previous or active HCMV infection
      in these patients.

PMID- 25949882
TI  - Potential of autologous NK cell therapy to eradicate leukemia: "Education is
      [not] the best provision for old age" -Aristotle.
AB  - B-precursor acute lymphoblastic leukemia (BP-ALL) patients are immunocompromised.
      We recently reported that functional natural killer (NK) cells can be grown from
      patient bone marrow and blood samples at diagnosis. Surprisingly, such NK cells
      exhibit cytotoxicity against autologous BP-ALL cells. Here, we outline unanswered
      questions, challenges and possible applications associated with these findings.

PMID- 25949881
TI  - The correlations between IL-17 vs. Th17 cells and cancer patient survival: a
      systematic review.
AB  - Both IL-17 and Th17 cells have been ascribed tumor promoting as well as tumor
      suppressing functions. We reviewed the literature on correlations between IL-17
      versus Th17 cells and survival in human cancer, following the PRISMA guidelines.
      Serum, formalin-fixed, paraffin-embedded (FFPE) tissue and peripheral blood
      samples were most frequently studied. High IL-17 quantities were correlated with
      poor prognosis, whereas high Th17 cell frequencies were correlated with improved
      prognosis. Since Th17 cells are a subpopulation of IL-17+ cells and had a
      different correlation with prognosis than total IL-17, we substantiate that a
      distinction should be made between Th17 and other IL-17+ cells.

PMID- 25949883
TI  - HIF-2alpha/ITPR1 axis: A new saboteur of NK-mediated lysis.
AB  - We recently investigated the role of von Hippel-Lindau (VHL) mutation and the
      subsequent induction of hypoxia-inducible factor 2alpha (HIF-2alpha) in the
      regulation of renal cell carcinoma (RCC) susceptibility to natural killer (NK)
      cell-mediated killing. We demonstrated that the resistance of VHL-mutated RCC
      cell line 786-0 to NK-mediated lysis requires HIF-2alpha and ITPR1, a direct
      novel target of HIF-2alpha, through the activation of autophagy in target cells
      by NK-derived signals.

PMID- 25949884
TI  - BRAF-inhibition and tumor immune suppression.
AB  - As BRAFV600E-inhibitors become standard treatment for many metastatic melanoma
      patients, research has begun to elucidate their impact on the tumor immune
      landscape. Here, we highlight our recent studies demonstrating the ability of
      melanoma cell-intrinsic BRAFV600E-inhibition to selectively reduce intratumoral
      immunosuppressive cell populations and enhance antitumor CD8+ T-cell immunity.

PMID- 25949885
TI  - Oncolytic virus expressing RANTES and IL-15 enhances function of CAR-modified T
      cells in solid tumors.
AB  - We improved the migration and survival of chimeric antigen receptor (CAR)
      modified T cells in solid tumors by combining CAR-T cells with an armed oncolytic
      virus. Local delivery of the chemokine RANTES and the cytokine IL-15 by the
      oncolytic virus enhanced the trafficking and persistence of the CAR-T cells,
      resulting in improved antitumor effects.

PMID- 25949886
TI  - In vivo profiling reveals immunomodulatory effects of sorafenib and dacarbazine
      on melanoma.
AB  - Sorafenib is a multi-kinase inhibitor used alone or in combination with
      dacarbazine to treat metastasized melanoma. Our study investigated the
      relationship between metabolic response assessed by PET-CT and global
      transcriptome changes during sorafenib and dacarbazine therapy in patients with
      advanced melanoma. We conducted an open-label, investigator-initiated study that
      enrolled 13 sorafenib-naive Stage IV melanoma patients, whose metastases were
      accessible for repeated biopsies. Treatment regimen included orally administered
      sorafenib and intravenous dacarbazine. Biopsies of skin or superficial lymph node
      metastases were taken before treatment (baseline), during sorafenib and after
      dacarbazine therapy and used for transcriptional profiling and validation
      experiments. Serum samples were evaluated for cytokine production. Metabolic
      response to therapy was observed in 45.5% of patients. The study drugs were well
      tolerated. We observed a clear upregulation of interferon (IFN)-stimulated immune
      response genes in profiled metastases. The IFNgamma-induced gene signature seemed
      to be enhanced after addition of dacarbazine to sorafenib. Serum IFNgamma also
      increased during therapy, particularly after addition of dacarbazine. Induction
      of IFNgamma stimulated genes correlating with increased serum IFNgamma was
      predictive of better clinical outcome and responders who had significantly higher
      serum IFNgamma levels lived longer. Our data reveal in situ changes in melanoma
      metastases during treatment with sorafenib and dacarbazine and suggest an
      additional mechanism of action through immunomodulation.

PMID- 25949887
TI  - Tumor immune remodeling by TGFbeta inhibition improves the efficacy of radiation
      therapy.
AB  - The tumor immune environment has been linked to prognosis in patients with a
      range of malignancies. Recently, we demonstrated in pre-clinical models that
      modifying the tumor immune environment using a small-molecule inhibitor of TGFb
      significantly improved outcome to subsequent radiation therapy. These data
      suggest that this and other immunotherapies may be used to remodel the tumor
      before conventional cancer therapies to improve outcomes.

PMID- 25949888
TI  - Targeting leukemia by CD1c-restricted T cells specific for a novel lipid antigen.
AB  - A subset of CD1c-restricted T lymphocytes exhibits strong reactivity against
      leukemia cells. These T cells recognize methyl-lysophosphatidic acid (mLPA), a
      novel lipid antigen produced by acute leukemia cells. Considering that CD1c
      restricted T cells display efficacious anti-leukemia activities in a mouse model,
      this lipid antigen thus represents a novel target in the immunotherapy of
      hematological malignancies.

PMID- 25949889
TI  - CTLs regulate tumor growth via cytostatic effects rather than cytotoxicity: a few
      T cells can influence the growth of many times more tumor cells.
AB  - Cytotoxic T lymphocytes (CTLs) play a central role in antitumor immunity. We
      utilized B16 melanoma cells expressing the fluorescent ubiquitination-based cell
      cycle indicator B16-fucci implanted in host mice and adoptively transferred with
      pmel-1-TCR transgenic T cells to demonstrate that tumor growth reduction is
      largely dependent on interferon gamma-mediated cell cycle arrest rather than the
      cytotoxic killing of tumor cells by CTLs.

PMID- 25949890
TI  - Non-V delta 2 gamma delta T lymphocytes as effectors of cancer immunotherapy.
AB  - Gamma delta T cells (gammadeltaT) are potent mediators of antitumor cytotoxicity
      and have shown promising efficacy in early phase clinical trials. Most is known
      about the tumoricidal properties of cells bearing the Vdelta2 T cell receptor
      chain, but recent studies have demonstrated that cells with the Vdelta1 chain and
      those with neither Vdelta1 nor Vdelta2 chains have properties which may make them
      more attractive anticancer effectors in adoptive immunotherapy.

PMID- 25949891
TI  - Reducing toxicity of 4-1BB costimulation: targeting 4-1BB ligands to the tumor
      stroma with bi-specific aptamer conjugates.
AB  - Systemic administration of immune modulatory antibodies to cancer patients is
      associated with autoimmune pathologies. We have developed a clinically feasible
      and broadly applicable approach to limit immune stimulation to disseminated tumor
      lesions using a bi-specific agonistic 4-1BB oligonucleotide aptamer targeted to a
      broadly expressed stromal product (e.g., VEGF or osteopontin). The stroma
      targeted aptamer conjugates engendered potent antitumor immunity against
      unrelated tumors and exhibited a superior therapeutic index compared to non
      targeted agonistic 4-1BB antibody.

PMID- 25949892
TI  - High endothelial venules are rare in colorectal cancers but accumulate in extra
      tumoral areas with disease progression.
AB  - Prolonged patient survival after surgical resection, is associated with a higher
      cytotoxic and memory T cell density within colorectal cancers (CRC). High
      endothelial venules (HEVs) are specialized blood vessels present in secondary
      lymphoid organs (SLO) that allow ingress of naive and central memory T cells from
      the blood. It has been proposed that HEVs in tumors might serve as a similar
      route of entry for lymphocytes into the tumor and result in an improved
      prognosis. The present study aimed to characterize HEVs and their
      microenvironment in resected tumors from colorectal cancer patients (n = 62). We
      observed HEVs in association with lymphoid aggregates in 49 out of 62 patients.
      However, these HEV+ lymphoid aggregates were largely at the invasive margin of
      the tumor and although there was an association with lymphocytes and HEVs at the
      invasive margin (p = 0.002) there was only a very weak association with tumor
      infiltrating lymphocytes. Indeed, lymphoid aggregates were associated with more
      advanced disease (Dukes' stage C) and did not indicate a favorable prognosis.

PMID- 25949893
TI  - Situational aldehyde dehydrogenase expression by regulatory T cells may explain
      the contextual duality of cyclophosphamide as both a pro-inflammatory and
      tolerogenic agent.
AB  - In two recent publications, we demonstrated that after allogeneic stimulation,
      regulatory T cells (Tregs) increase expression of aldehyde dehydrogenase (ALDH),
      the major in vivo mechanism of cyclophosphamide detoxification, thereby becoming
      cyclophosphamide resistant. Differential ALDH expression may explain why
      cyclophosphamide has pro- and anti-inflammatory effects that are temporally and
      contextually dependent.

PMID- 25949894
TI  - An immunogenomic stratification of colorectal cancer: Implications for
      development of targeted immunotherapy.
AB  - Although tumor infiltrating lymphocyte (TIL) density is prognostic and predictive
      in colorectal cancer (CRC), the impact of tumor genetics upon colorectal
      immunobiology is unclear. Identification of genetic factors that influence the
      tumor immunophenotype is essential to improve the effectiveness of stratified
      immunotherapy approaches. We carried out a bioinformatics analysis of CRC data in
      The Cancer Genome Atlas (TCGA) involving two-dimensional hierarchical clustering
      to define an immune signature that we used to characterize the immune response
      across key patient groups. An immune signature termed The Co-ordinate Immune
      Response Cluster (CIRC) comprising 28 genes was coordinately regulated across the
      patient population. Four patient groups were delineated on the basis of cluster
      expression. Group A, which was heavily enriched for patients with microsatellite
      instability (MSI-H) and POL mutations, exhibited high CIRC expression, including
      the presence of several inhibitory molecules: CTLA4, PDL1, PDL2, LAG3, and TIM3.
      In contrast, RAS mutation was enriched in patient groups with lower CIRC
      expression. This work links the genetics and immunobiology of colorectal
      tumorigenesis, with implications for the development of stratified
      immunotherapeutic approaches. Microsatellite instability and POL mutations are
      linked with high mutational burden and high immune infiltration, but the
      coordinate expression of inhibitory pathways observed suggests combination
      checkpoint blockade therapy may be required to improve efficacy. In contrast, RAS
      mutant tumors predict for a relatively poor immune infiltration and low
      inhibitory molecule expression. In this setting, checkpoint blockade may be less
      efficacious, highlighting a requirement for novel strategies in this patient
      group.

PMID- 25949895
TI  - The ins and outs of osteopontin.
AB  - The continuous remodeling of progressing tumors demands non-physiologic
      production of extracellular matrix (ECM) proteins. Among them, osteopontin (OPN)
      has been largely involved in tumor progression and metastasis. We have recently
      discovered a new mechanism for OPN in the metastatic spread of mammary carcinoma
      providing local immunosuppression at the seeding site.

PMID- 25949896
TI  - Neutralization of membrane complement regulators improves complement-dependent
      effector functions of therapeutic anticancer antibodies targeting leukemic cells.
AB  - Complement-dependent cytotoxicity (CDC) is one of the effector mechanisms
      mediated by therapeutic anticancer monoclonal antibodies (mAbs). However, the
      efficacy of antibodies is limited by the resistance of malignant cells to
      complement attack, primarily due to the over-expression of one or more membrane
      complement regulatory proteins (mCRPs) CD46, CD55, and CD59. CD20-positive
      Burkitt lymphoma Raji cells and primary CLL cells are resistant to rituximab
      (RTX)-induced CDC whereas ofatumumab (OFA) proved to be more efficient in cell
      killing. Primary CLL cells but not CD52-positive acute lymphoblastic leukemia
      (ALL) REH cells were sensitive to alemtuzumab (ALM)-induced CDC. Upon combined
      inhibition on Raji and CLL cells by mCRPs-specific siRNAs or neutralizing
      antibodies, CDC induced by RTX and by OFA was augmented. Similarly, CDC of REH
      cells was enhanced after mCRPs were inhibited upon treatment with ALM. All mAbs
      induced C3 opsonization, which was significantly augmented upon blocking mCRPs.
      C3 opsonization led to enhanced cell-mediated cytotoxicity of leukemia cells
      exposed to PBLs or macrophages. Furthermore, opsonized CLL cells were efficiently
      phagocytized by macrophages. Our results provide conclusive evidence that
      inhibition of mCRPs expression sensitizes leukemic cells to complement attack
      thereby enhancing the therapeutic effect of mAbs targeting leukemic cells.

PMID- 25949898
TI  - Targeting tumor-associated myeloid cells for cancer immunotherapy.
AB  - Tumor-associated myeloid cells undermine the therapeutic efficacy of cancer
      immunotherapy by their inhibitory properties on immune effector cells.
      Development of therapeutic agents to deplete suppressive myeloid cells in tumor
      microenvironment requires identification of cell-specific targets. A competitive
      phage display technique on live cells paves the way to discovery of such a
      target.

PMID- 25949897
TI  - Characterization of the in vivo immune network of IDO, tryptophan metabolism, PD
      L1, and CTLA-4 in circulating immune cells in melanoma.
AB  - In melanoma, both the induction of immunosuppression by tumor cells and the
      inflammatory antitumor response can induce an upregulation of counter-regulatory
      mechanisms such as indoleamine 2,3-dioxygenase (IDO), programmed death-ligand 1
      (PD-L1) and CTLA-4+ regulatory T-cells (Tregs) in the tumor microenvironment.
      Even though these immunosuppressive mediators are targets for immunotherapy,
      research investigating their expression in the peripheral blood is lacking. We
      therefore, performed flow cytometry on PBMCs of stage I-IV melanoma patients. IDO
      expression was detected in plasmacytoid dendritic cells (pDC) and monocytic
      myeloid-derived suppressor cells (mMDSC), and increased in advanced disease stage
      (p = 0.027). Tryptophan breakdown confirmed the functional activity of IDO and
      was linked with increased PD-L1+ cytotoxic T-cells (p = 0.009), relative
      lymphopenia (p = 0.036), and a higher mDC/pDC ratio (p = 0.002). High levels of
      circulating PD-L1+ cytotoxic T-cells were associated with increased CTLA-4
      expression by Tregs (p = 0.005) and MDSC levels (p = 0.033). This illustrates
      that counter-regulatory immune mechanisms in melanoma should be considered as one
      interrelated signaling network. Moreover, both increased PD-L1+ T-cells and CTLA
      4 expression in Tregs conferred a negative prognosis, indicating their in vivo
      relevance. Remarkably, circulating CTLA-4, IDO, and pDC levels were altered
      according to prior invasion of the sentinel lymph node and IDO expression in the
      sentinel was associated with more IDO+ PBMCs. We conclude that the expression of
      IDO, PD-L1, and CTLA-4 in the peripheral blood of melanoma patients is strongly
      interconnected, associated with advanced disease and negative outcome,
      independent of disease stage. Combination treatments targeting several of these
      markers are therefore likely to exert a synergistic response.

PMID- 25949899
TI  - Author's view: radiation and immunotherapy as systemic therapy for solid tumors.
AB  - The ability of tumors to evade detection by the immune system via inducing
      immunosuppression prompted the therapeutic development of immune checkpoint
      inhibitors. In our recent review, we discussed findings from preclinical and
      clinical investigations of these agents utilized in combination with radiation
      inducing abscopal (systemic) antitumor effects.

PMID- 25949900
TI  - Resistance of cyclooxygenase-2 expressing pancreatic ductal adenocarcinoma cells
      against gammadelta T cell cytotoxicity.
AB  - The prostaglandin (PG) synthetase cyclooxygenase 2 (Cox-2) promotes
      tumorigenesis, tumor progression, and metastasis in a variety of human cancer
      entities including pancreatic ductal adenocarcinoma (PDAC). In this study, we
      demonstrate that in PDAC cells such as Colo357 cells, enhanced Cox-2 expression
      and increased release of the Cox-2 metabolite prostaglandin E2 (PGE2) promotes
      resistance against gammadelta T cell-mediated lysis. Co-culture with activated
      gammadelta T cells induced an upregulation of Cox-2 expression in Colo357 cells,
      and thereby an enhanced PGE2 release, in response to tumor necrosis factor alpha
      (TNFalpha) secretion from gammadelta T cells. The PGE2-mediated inhibition of
      gammadelta T cell cytotoxicity against Cox-2-expressing PDAC cells can be
      partially overcome by Cox-2 inhibitors. Our results show that differences between
      PDAC cells in regards to sensitivity to gammadelta T-cell cytotoxicity can be due
      to distinct levels of Cox-2 expression associated with varying amounts of PGE2
      release. While gammadelta T cell cytotoxicity against PDAC cells expressing low
      levels of Cox-2 can be effectively enhanced by tribody [(Her2)2*Vgamma9] with
      specificity for Vgamma9 T cell receptor and HER-2/neu on PDAC cells, a
      combination of tribody [(Her2)2*Vgamma9] and Cox-2 inhibitor is necessary to
      induce complete lysis of Cox-2 high expressing Colo357. In conclusion, our
      results suggest that the application of tribody [(Her2)2*Vgamma9] that enhances
      gammadelta T-cell cytotoxicity and Cox-2 inhibitors that overcome PGE2-mediated
      resistance of PDAC cells to the cytotoxic activity of gammadelta T cells might
      offer a promising combined immunotherapy for pancreatic cancer.

PMID- 25949901
TI  - In situ immunization via non-surgical ablation to prevent local and distant tumor
      recurrence.
AB  - Host immunities are induced during cryoablation or oncolytic adenovirus therapy
      when the entire repertoire of tumor associated antigens (TAA) is released. Local
      and systemic protection is enhanced by the combined treatment with toll-like
      receptor agonist or immune stimulating cytokines. Non-surgical tumor ablation is
      an effective platform for in situ immunization.

PMID- 25949903
TI  - Serum HMGB1 is a predictive and prognostic biomarker for oncolytic immunotherapy.
AB  - With the emergence of effective immunotherapeutics, which nevertheless harbor the
      potential for toxicity and are expensive to use, biomarkers are urgently needed
      for identification of cancer patients who respond to treatment. In this clinical
      epidemiological study of 202 cancer patients treated with oncolytic adenoviruses,
      we address the biomarker value of serum high-mobility group box 1 (HMGB1)
      protein. Overall survival and imaging responses were studied as primary endpoints
      and adjusted for confounding factors in two multivariate analyses (Cox and
      logistic regression). Mechanistic studies included assessment of circulating
      tumor-specific T-cells by ELISPOT, virus replication by quantitative PCR, and
      inflammatory cytokines by cytometric bead array. Patients with low HMGB1 baseline
      levels (below median concentration) showed significantly improved survival (p =
      0.008, Log-Rank test) and radiological disease control rate (49.2% vs. 30.0%, p =
      0.038, chi2 test) as compared to high-baseline patients. In multivariate
      analyses, the low HMGB1 baseline status was a strong prognostic (HR 0.638, 95% CI
      0.462-0.881) and the best predictive factor for disease control (OR 2.618, 95% CI
      1.004-6.827). Indicative of an immune-mediated mechanism, antitumor T-cell
      activity in blood and response to immunogenic-transgene coding viruses associated
      with improved outcome only in HMGB1-low patients. Our results suggest that serum
      HMGB1 baseline is a useful prognostic and predictive biomarker for oncolytic
      immunotherapy with adenoviruses, setting the stage for prospective clinical
      studies.

PMID- 25949904
TI  - Collaborative effects between the TNFalpha-TNFR1-macrophage axis and the VEGF-C
      VEGFR3 signaling in lymphangiogenesis and metastasis.
AB  - Although inflammation and metastasis are two well-known hallmarks of malignant
      disease, the relationship between inflammation and lymphatic metastasis is an
      unexplored research area. We recently elucidated a sophisticated mechanism by
      which TNFalpha-induced tumor inflammation conscripts macrophage-mediated VEGF-C
      VEGFR3 signaling in lymphangiogenesis and metastasis.

PMID- 25949902
TI  - Sunitinib depletes myeloid-derived suppressor cells and synergizes with a cancer
      vaccine to enhance antigen-specific immune responses and tumor eradication.
AB  - The high efficacy of therapeutic cancer vaccines in preclinical studies has yet
      to be fully achieved in clinical trials. Tumor immune suppression is a critical
      factor that hampers the desired antitumor effect. Here, we analyzed the combined
      effect of a cancer vaccine and the receptor tyrosine kinase inhibitor sunitinib.
      Sunitinib was administered intraperitoneally, alone or in combination with
      intramuscular immunization using a viral vector based cancer vaccine composed of
      Semliki Forest virus replicon particles and encoding the oncoproteins E6 and E7
      (SFVeE6,7) of human papilloma virus (HPV). We first demonstrated that treatment
      of tumor-bearing mice with sunitinib alone dose-dependently depleted myeloid
      derived suppressor cells (MDSCs) in the tumor, spleen and in circulation.
      Concomitantly, the number of CD8+ T cells increased 2-fold and, on the basis of
      CD69 expression, their activation status was greatly enhanced. The intrinsic
      immunosuppressive activity of residual MDSCs after sunitinib treatment was not
      changed in a dose-dependent fashion. We next combined sunitinib treatment with
      SFVeE6,7 immunization. This combined treatment resulted in a 1.5- and 3-fold
      increase of E7-specific cytotoxic T lymphocytes (CTLs) present within the
      circulation and tumor, respectively, as compared to immunization only. The ratio
      of E7-specific CTLs to MDSCs in blood thereby increased 10- to 20-fold and in
      tumors up to 12.5-fold. As a result, the combined treatment strongly enhanced the
      antitumor effect of the cancer vaccine. This study demonstrates that sunitinib
      creates a favorable microenvironment depleted of MDSCs and acts synergistically
      with a cancer vaccine resulting in enhanced levels of active tumor-antigen
      specific CTLs, thus changing the balance in favor of antitumor immunity.

PMID- 25949905
TI  - Cancer stem cell vaccine inhibits metastases of primary tumors and induces
      humoral immune responses against cancer stem cells.
AB  - The inability to target cancer stem cells (CSC) may be a significant factor
      contributing to treatment failure. We have developed a strategy to target the CSC
      populations in melanoma and squamous cell carcinoma using CSC lysate-pulsed
      dendritic cells (DCs). The CSC-DC vaccine was administered in the adjuvant
      setting after localized radiation therapy of established tumors. Using mouse
      models we demonstrated that DCs pulsed with CSCs enriched by virtue of their
      expression of the CSC marker ALDH (termed CSC-DC) significantly inhibited tumor
      growth, reduced development of pulmonary metastases and prolonged survival. The
      effect was associated with downregulation of chemokine (C-C motif) receptors CCR7
      and CCR10 in tumor cells and decreased expression of the chemokine (C-C motif)
      ligands CCL21, CCL27 and CCL28 in lung tissue. The CSC-DC vaccine significantly
      reduced ALDHhigh CSC frequency in primary tumors. Direct targeting of CSCs was
      demonstrated by the specific binding of IgG produced by ALDHhigh CSC-DC vaccine
      primed B cells to ALDHhigh CSCs, resulting in lysis of these target CSCs in the
      presence of complement. These data suggest that the CSC-DC vaccine approach may
      be useful in the adjuvant setting where local and systemic relapse are high after
      conventional treatment of cancers.

PMID- 25949906
TI  - Tumor-associated and immunochemotherapy-dependent long-term alterations of the
      peripheral blood NK cell compartment in DLBCL patients.
AB  - Natural Killer (NK) cells are a key component of tumor immunosurveillance and
      thus play an important role in rituximab-dependent killing of lymphoma cells via
      an antibody-dependent cellular cytotoxicity (ADCC) mechanism. We evaluated the
      phenotypic and functional assets of peripheral blood NK cell subsets in 32 newly
      diagnosed diffuse large B-cell lymphoma (DLBCL) patients and in 27 healthy
      controls. We further monitored long-term modifications of patient NK cells for up
      to 12 months after rituximab-based immunochemotherapy. At diagnosis, patients
      showed a higher percentage of CD56dim and CD16+ NK cells, and a higher frequency
      of GrzB+ cells in CD56dim, CD56bright, and CD16+ NK cell subsets than healthy
      controls. Conversely, DLBCL NK cell killing and interferon gamma (IFNgamma)
      production capability were comparable to those derived from healthy subjects.
      Notably, NK cells from refractory/relapsed patients exhibited a lower "natural"
      cytotoxicity. A marked and prolonged therapy-induced reduction of both "natural"
      and CD16-dependent NK cytotoxic activities was accompanied by the down-modulation
      of CD16 and NKG2D activating receptors, particularly in the CD56dim subset.
      However, reduced NK cell killing was not associated with defective lytic granule
      content or IFNgamma production capability. This study firstly describes tumor
      associated and therapy-induced alterations of the systemic NK cell compartment in
      DLBCL patients. As these alterations may negatively impact rituximab-based
      therapy efficacy, our work may provide useful information for improving
      immunochemotherapeutic strategies.

PMID- 25949907
TI  - NKT cell-targeted vaccination plus anti-4-1BB antibody generates persistent CD8 T
      cell immunity against B cell lymphoma.
AB  - Harnessing the immune adjuvant properties of natural killer T (NKT) cells is an
      effective strategy to generate anticancer immunity. The objective of this study
      was to increase the potency and durability of vaccine-induced immunity against B
      cell lymphoma by combining alpha-galactosylceramide (alpha-GalCer)-loaded tumor
      cell vaccination with an agonistic antibody targeting the immune checkpoint
      molecule 4-1BB (CD137). We observed potent synergy when combining vaccination and
      anti-4-1BB antibody treatment resulting in significantly enhanced survival of
      mice harboring EMU-myc tumors, including complete eradication of lymphoma in over
      50% of mice. Tumor-free survival required interferon gamma (IFNgamma)-dependent
      expansion of CD8+ T cells and was associated with 4-1BB-mediated differentiation
      of KLRG1+ effector CD8+ T cells. 'Cured' mice were also resistant to lymphoma re
      challenge 80 days later indicating successful generation of immunological memory.
      Overall, our results demonstrate that therapeutic anticancer vaccination against
      B cell lymphoma using an NKT cell ligand can be boosted by subsequent co
      stimulation through 4-1BB leading to a sustainable immune response that may
      enhance outcomes to conventional treatment.

PMID- 25949909
TI  - miR-23a blockade enhances adoptive T cell transfer therapy by preserving immune
      competence in the tumor microenvironment.
AB  - In adoptive T cell transfer therapy (ACT), the antitumor efficacy of cytotoxic
      CD8+ T lymphocytes (CTLs) has been limited by tumor-induced immunosuppression. We
      have demonstrated that miR-23a blockade in tumor-specific CTLs conferred
      resilience to TGFbeta-mediated immunosuppression, resulting in superior tumor
      control. Our studies highlight miR-23a in tumor-specific CTLs as a clinically
      relevant target to enhance ACT.

PMID- 25949908
TI  - CD8+/FOXP3+-ratio in osteosarcoma microenvironment separates survivors from non
      survivors: a multicenter validated retrospective study.
AB  - Osteosarcoma is the most common primary bone tumor characterized by juvenile
      onset, tumor heterogeneity, and early pulmonary metastasis. Therapeutic
      improvement stagnates since more than two decades. Unlike major malignancies,
      biomarkers as prognostic factors at time of diagnosis are missing. Disease
      rareness hampers study recruitment of patient numbers sufficient to outweigh
      tumor heterogeneity. Here, we analyzed in a multicenter cohort the osteosarcoma
      microenvironment to reduce effects of tumor cell heterogeneity. We hypothesized
      that quantitative ratios of intratumoral CD8+T-cells to FOXP3+T-cells
      (CD8+/FOXP3+-ratios) provide strong prognostic information when analyzed by whole
      slide imaging in diagnostic biopsies. We followed recommendations-for-tumor
      marker-prognostic-studies (REMARK). From 150 included cases, patients with
      complete treatment were identified and assigned to the discovery (diagnosis
      before 2004) or the validation cohort (diagnosis 2004-2012). Highly standardized
      immunohistochemistry of CD8+ and FOXP3+, which was validated by methylation
      specific gene analysis, was performed followed by whole-slide analysis and
      clinical outcome correlations. We observed improved estimated survival in
      patients with CD8+/FOXP3+-ratios above the median (3.08) compared to patients
      with lower CD8+/FOXP3+-ratios (p = 0.000001). No patients with a CD8+/FOXP3+
      ratio above the third quartile died within the observation period (median follow
      up 69 mo). Multivariate analysis demonstrated independence from current
      prognostic factors including metastasis and response to neoadjuvant chemotherapy.
      Data from an independent validation cohort confirmed improved survival (p =
      0.001) in patients with CD8+/FOXP3+-ratios above 3.08. Multivariate analysis
      proofed that this observation was also independent from prognostic factors at
      diagnosis within the validation cohort. Intratumoral CD8+/FOXP3+-ratio in
      pretreatment biopsies separates patients with prolonged survival from non
      survivors in osteosarcoma.

PMID- 25949910
TI  - Metabolic perturbation sensitizes human breast cancer to NK cell-mediated
      cytotoxicity by increasing the expression of MHC class I chain-related A/B.
AB  - Cleavage or shedding of the surface antigen, MHC class I chain-related (MIC)
      protein (A/B) has been known to be one of the mechanisms by which tumor cells
      escape host immune surveillance. Thus, any strategy to augment the surface
      expression of MICA/B could facilitate anticancer immune response. Here, we
      demonstrate that metabolic perturbation by the glycolytic inhibitor, 3
      bromopyruvate (3-BrPA) augments the surface expression of MICA/B in human breast
      cancer cell lines, MDA-MB-231 and T47D. Data from in vitro studies show that a
      non-toxic, low-dose of 3-BrPA is sufficient to perturb energy metabolism, as
      evident by the activation of p-AMPK, p-AKT and p-PI3K. Further, 3-BrPA-treatment
      also elevated the levels of MICA/B in human breast cancer cell lines.
      Significantly, 3-BrPA-dependent increase in MICA/B levels also enhanced the
      sensitivity of cancer cells to natural killer (NK-92MI)-mediated cytotoxicity. In
      vivo, 3-BrPA-pretreated cells demonstrated greater sensitivity to NK-92MI therapy
      than their respective controls. The antitumor effect was confirmed by a reduction
      in tumor size and decreased tumor viability as observed by bioluminescence
      imaging. Histological examination and TUNEL staining demonstrated that NK-92MI
      administration promoted apoptosis in 3-BrPA-pretreated cells. Taken together, our
      data show that targeting energy metabolism could be a novel strategy to enhance
      the effectiveness of anticancer immunotherapeutics.

PMID- 25949912
TI  - Dual roles of TLR7 in the lung cancer microenvironment.
AB  - Toll-like receptor 7 (TLR7) agonists are under investigation for their ability to
      enhance antitumor immune responses. However, these agonists can also stimulate
      TLR7-expressing tumor cells. High TLR7 expression in the primary tumor confers
      poor clinical outcome and resistance to chemotherapy in lung cancer patients.
      This protumorigenic effect of TLR7 has been validated in murine models of lung
      carcinoma.

PMID- 25949911
TI  - Human NK cells activated by EBV+ lymphoblastoid cells overcome anti-apoptotic
      mechanisms of drug resistance in haematological cancer cells.
AB  - Natural killer (NK) cells recognize and eliminate transformed or infected cells
      that have downregulated MHC class-I and express specific activating ligands.
      Recent evidence indicates that allogeneic NK cells are useful to eliminate
      haematological cancer cells independently of MHC-I expression. However, it is
      unclear if transformed cells expressing mutations that confer anti-apoptotic
      properties and chemoresistance will be susceptible to NK cells. Allogeneic
      primary human NK cells were activated using different protocols and prospectively
      tested for their ability to eliminate diverse mutant haematological and apoptotic
      resistant cancer cell lines as well as patient-derived B-cell chronic lymphocytic
      leukemia cells with chemotherapy multiresistance. Here, we show that human NK
      cells from healthy donors activated in vitro with Epstein Barr virus positive
      (EBV+)-lymphoblastoid cells display an enhanced cytotoxic and proliferative
      potential in comparison to other protocols of activation such a K562 cells plus
      interleukin (IL)2. This enhancement enables them to kill more efficiently a
      variety of haematological cancer cell lines, including a panel of transfectants
      that mimic natural mutations leading to oncogenic transformation and
      chemoresistance (e.g., overexpression of Bcl-2, Bcl-XL and Mcl-1 or
      downregulation of p53, Bak/Bax or caspase activity). The effect was also observed
      against blasts from B-cell chronic lymphocytic leukemia patients showing multi
      resistance to chemotherapy. Our findings demonstrate that particular in vitro
      activated NK cells may overcome anti-apoptotic mechanisms and oncogenic
      alterations frequently occurring in transformed cells, pointing toward the use of
      EBV+-lymphoblastoid cells as a desirable strategy to activate NK cells in vitro
      for the purpose of treating haematological neoplasia with poor prognosis.

PMID- 25949913
TI  - Kynurenine and uric acid levels in chronic myeloid leukemia patients.
AB  - Indoleamine 2,3-dioxygenase 1 (IDO1), IDO2 and tryptophan 2,3-dioxygenase (TDO)
      represent some of the key immune regulators. Their increased activity has been
      demonstrated in a number of human malignancies but not yet in chronic myeloid
      leukemia (CML). In the present study, the activity of these enzymes was tested in
      29 CML patients and 28 healthy subjects by monitoring the kynurenine
      (KYN)/tryptophan ratio. Serum samples taken prior to the therapy displayed a
      highly significant difference in KYN levels between the patient and control
      groups. However, increased KYN levels were detected in only 13 (44.8%) of these
      CML patients. The KYN levels in pretreatment sera of the patients correlated with
      the tumor burden. There was also a strong correlation between KYN levels and uric
      acid levels (UA). This suggests but does not prove the possible involvement of UA
      in activating IDO family of enzymes. Whenever tested, the increased KYN levels
      normalized in the course of the therapy. Patients with normal KYN levels in their
      pretreatment sera and subsequently treated with interferon-alpha, showed a
      transitory increase in their KYN levels. The present data indicate that CML
      should be added to the malignancies with an increased activity of the IDO family
      of enzymes and suggest that IDO inhibitors may be used in the treatment of CML
      patients.

PMID- 25949915
TI  - CD4+ T cell plasticity engenders robust immunity in response to cytokine therapy.
AB  - CD4+ T cells represent an entire arm of the immune system that has hitherto been
      incompletely understood, but their potential to act as both helper and effector
      may make them optimal protagonists in immunotherapeutic approaches to treat
      cancer. Cytokine therapy can activate this population in a manner that ensures
      maximal diversification of effector function for a robust immune response.

PMID- 25949914
TI  - Ex vivo expanded human circulating Vdelta1 gammadeltaT cells exhibit favorable
      therapeutic potential for colon cancer.
AB  - Gamma delta T (gammadeltaT) cells are innate-like lymphocytes with strong, MHC
      unrestricted cytotoxicity against cancer cells and show a promising prospect in
      adoptive cellular immunotherapy for various malignancies. However, the clinical
      outcome of commonly used Vgamma9Vdelta2 gammadeltaT (Vdelta2 T) cells in adoptive
      immunotherapy for most solid tumors is limited. Here, we demonstrate that freshly
      isolated Vdelta1 gammadeltaT (Vdelta1 T) cells from human peripheral blood (PB)
      exhibit more potent cytotoxicity against adherent and sphere-forming human colon
      cancer cells than Vdelta2 T cells in vitro. We also develop an optimized protocol
      to preferentially expand Vdelta1 T cells isolated from PB of both healthy donors
      and colon cancer patients by in vitro short-term culture with phytohemagglutinin
      (PHA) and interleukin-7 (IL-7). Expanded Vdelta1 T cells highly expressed
      cytotoxicity-related molecules, chemokine receptors and cytokines with enhanced
      cytolytic effect against adherent and sphere-forming colon cancer cells in a cell
      to-cell contact dependent manner. In addition, PHA and IL-7 expanded Vdelta1 T
      cells showed proliferation and survival advantage partly through an IL-2
      signaling pathway. Furthermore, ex vivo expanded Vdelta1 T cells also restrained
      the tumor growth and prolonged the tumor-burdened survival of human colon
      carcinoma xenografted mice. Our findings suggest that human PB Vdelta1 T cells
      expanded by PHA and IL-7 are a promising candidate for anticancer adoptive
      immunotherapy for human solid tumors such as colon cancer.

PMID- 25949916
TI  - Novel role of hematopoietic stem cells in immunologic rejection of malignant
      gliomas.
AB  - Adoptive cellular therapy (ACT) after lymphodepletive conditioning can induce
      dramatic clinical responses, but this approach has been largely limited to
      melanoma due to a lack of reliable methods for expanding tumor-specific
      lymphocytes from the majority of other solid cancers. We have employed tumor RNA
      pulsed dendritic cells (DCs) to reliably expand CD4+ and CD8+ tumor-reactive T
      lymphocytes for curative ACT in a highly-invasive, chemotherapy- and radiation
      resistant malignant glioma model. Curative treatment of established intracranial
      tumors involved a synergistic interaction between myeloablative (MA)
      conditioning, adoptively transferred tumor-specific T cells, and tumor RNA-pulsed
      DC vaccines. Hematopoietic stem cells (HSCs), administered for salvage from MA
      conditioning, rapidly migrated to areas of intracranial tumor growth and
      facilitated the recruitment of tumor-specific lymphocytes through HSC-elaborated
      chemokines and enhanced immunologic rejection of intracranial tumors during ACT.
      Furthermore, HSC transplant under non-myeloablative (NMA) conditions also
      enhanced immunologic tumor rejection, indicating a novel role for the use of HSCs
      in the immunologic treatment of malignant gliomas and possibly other solid
      tumors.

PMID- 25949917
TI  - Enhancing chemotherapy efficacy by reprogramming the senescence-associated
      secretory phenotype of prostate tumors: A way to reactivate the antitumor
      immunity.

PMID- 25949919
TI  - Controlling T cell senescence in the tumor microenvironment for tumor
      immunotherapy.
AB  - Understanding molecular mechanisms involved in creating and sustaining the tumor
      suppressive microenvironment is critical for the development of novel antitumor
      therapeutic strategies. We have identified the induction of T cell senescence as
      a novel mechanism utilized by human tumor cells to induce immune suppression, and
      provided a new strategy using TLR8 ligands to reverse tumor immunosuppressive
      effects for tumor immunotherapy.

PMID- 25949918
TI  - Combating HER2-overexpressing breast cancer through induction of calreticulin
      exposure by Tras-Permut CrossMab.
AB  - Although trastuzumab has succeeded in breast cancer treatment, acquired
      resistance is one of the prime obstacles for breast cancer therapies. There is an
      urgent need to develop novel HER2 antibodies against trastuzumab resistance.
      Here, we first rational designed avidity-imporved trastuzumab and pertuzumab
      variants, and explored the correlation between the binding avidity improvement
      and their antitumor activities. After characterization of a pertuzumab variant
      L56TY with potent antitumor activities, a bispecific immunoglobulin G-like
      CrossMab (Tras-Permut CrossMab) was generated from trastuzumab and binding
      avidity-improved pertuzumab variant L56TY. Although, the antitumor efficacy of
      trastuzumab was not enhanced by improving its binding avidity, binding avidity
      improvement could significantly increase the anti-proliferative and antibody
      dependent cellular cytotoxicity (ADCC) activities of pertuzumab. Further studies
      showed that Tras-Permut CrossMab exhibited exceptional high efficiency to inhibit
      the progression of trastuzumab-resistant breast cancer. Notably, we found that
      calreticulin (CRT) exposure induced by Tras-Permut CrossMab was essential for
      induction of tumor-specific T cell immunity against tumor recurrence. These data
      indicated that simultaneous blockade of HER2 protein by Tras-Permut CrossMab
      could trigger CRT exposure and subsequently induce potent tumor-specific T cell
      immunity, suggesting it could be a promising therapeutic strategy against
      trastuzumab resistance.

PMID- 25949920
TI  - Tregs activated by bispecific antibodies: Killers or suppressors?
AB  - In recent years, bispecific antibodies (bsAb) have emerged as promising tools for
      a target-specific redirection of T cells in order to eliminate malignant cells.
      However, CD3-engaging constructs might also activate T regulatory cells (Tregs)
      present in the tumor microenvironment. Whether this has detrimental or beneficial
      effects for tumor therapy is still controversially discussed.

PMID- 25949921
TI  - IL-12 secreting tumor-targeted chimeric antigen receptor T cells eradicate
      ovarian tumors in vivo.
AB  - A novel approach for the treatment of ovarian cancer includes immunotherapy with
      genetically engineered T cells targeted to ovarian cancer cell antigens. Using
      retroviral transduction, T cells can be created that express an artificial T cell
      receptor (TCR) termed a chimeric antigen receptor (CAR). We have generated a CAR,
      4H11-28z, specific to MUC-16ecto antigen, which is the over-expressed on a
      majority of ovarian tumor cells and is the retained portion of MUC-16 after
      cleavage of CA-125. We previously demonstrated that T cells modified to express
      the 4H11-28z CAR eradicate orthotopic human ovarian cancer xenografts in SCID
      Beige mice. However, despite the ability of CAR T cells to localize to tumors,
      their activation in the clinical setting can be inhibited by the tumor
      microenvironment, as is commonly seen for endogenous antitumor immune response.
      To potentially overcome this limitation, we have recently developed a construct
      that co-expresses both MUC16ecto CAR and IL-12 (4H11-28z/IL-12). In vitro, 4H11
      28z/IL-12 CAR T cells show enhanced proliferation and robust IFNgamma secretion
      compared to 4H11-28z CAR T cells. In SCID-Beige mice with human ovarian cancer
      xenografts, IL-12 secreting CAR T cells exhibit enhanced antitumor efficacy as
      determined by increased survival, prolonged persistence of T cells, and higher
      systemic IFNgamma. Furthermore, in anticipation of translating these results into
      a phase I clinical trial which will be the first to study IL-12 secreting CAR T
      cells in ovarian cancer, an elimination gene has been included to allow for
      deletion of CAR T cells in the context of unforeseen or off-tumor on-target
      toxicity.

PMID- 25949922
TI  - Characterization of the myeloid-derived suppressor cell subset regulated by NK
      cells in malignant lymphoma.
AB  - Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population with the
      ability to suppress immune responses and are currently classified into three
      distinct MDSC subsets: monocytic, granulocytic and non-monocytic, and non
      granulocytic MDSCs. Although NK cells provide an important first-line defense
      against newly transformed cancer cells, it is unknown whether NK cells can
      regulate MDSC populations in the context of cancer. In this study, we initially
      found that the frequency of MDSCs in non-Hodgkin lymphoma (NHL) patients was
      increased and inversely correlated with that of NK cells, but not that of T
      cells. To investigate the regulation of MDSC subsets by NK cells, we used an EL4
      murine lymphoma model and found the non-monocytic and non-granulocytic MDSC
      subset, i.e., Gr1+CD11b+Ly6GmedLy6Cmed MDSC, is increased after NK cell
      depletion. The MDSC population that expresses MHC class II, CD80, CD124, and CCR2
      is regulated mainly by CD27+CD11b+NK cells. In addition, this MDSC subset
      produces some immunosuppressive cytokines, including IL-10 but not nitric oxide
      (NO) or arginase. We also examined two subsets of MDSCs (CD14+HLA-DR- and CD14-
      HLA-DR- MDSC) in NHL patients and found that higher IL-10-producing CD14+HLA-DR
      MDSC subset can be seen in lymphoma patients with reduced NK cell frequency in
      peripheral blood. Our analyses of MDSCs in this study may enable a better
      understanding of how MDSCs manipulate the tumor microenvironment and are
      regulated by NK cells in patients with lymphoma.

PMID- 25949923
TI  - The combination of a novel immunomodulator with a regulatory T cell suppressing
      antibody (DTA-1) regress advanced stage B16F10 solid tumor by repolarizing tumor
      associated macrophages in situ.
AB  - Tumor associated macrophages and tumor infiltrating regulatory T cells greatly
      hamper host-protective antitumor responses. Therefore, we utilized a novel
      immunomodulator, heat-killed Mycobacterium indicus pranii (Mw), to repolarize TAM
      and an agonistic GITR antibody (DTA-1) to reduce intratumoral regulatory T cell
      frequency for generation of a host-protective antitumor response. Although, the
      combination of Mw and DTA-1was found to be effective against advanced stage
      tumors, however, Mw or DTA-1 failed to do so when administered individually. The
      presence of high level of regulatory T cells abrogated the only Mw induced
      antitumor functions, whereas only DTA-1 treatment was found to be ineffective due
      to its inability to induce TAM repolarization in vivo. The combination therapy
      was found to be effective since DTA-1 treatment reduced the frequency of
      regulatory T cells to such an extent where they could not attenuate Mw induced
      TAM repolarization in vivo. Therefore, the combination therapy involving Mw and
      DTA-1 may be utilized to the success of advanced stage solid tumor
      immunotherapies.

PMID- 25949924
TI  - Natural killer T cell activation overcomes immunosuppression to enhance clearance
      of postsurgical breast cancer metastasis in mice.
AB  - Metastatic lesions are responsible for over 90% of breast cancer associated
      deaths. Therefore, strategies that target metastasis are of particular interest.
      This study examined the efficacy of natural killer T (NKT) cell activation as a
      post-surgical immunotherapy in a mouse model of metastatic breast cancer.
      Following surgical resection of orthotopic 4T1 mammary carcinoma tumors, BALB/c
      mice were treated with NKT cell activating glycolipid antigens (alpha-GalCer,
      alpha-C-GalCer or OCH) or alpha-GalCer-loaded dendritic cells (DCs). Low doses of
      glycolipids transiently reduced metastasis but did not increase survival. A high
      dose of alpha-GalCer enhanced overall survival, but was associated with increased
      toxicity and mortality at early time points. Treatment with alpha-GalCer-loaded
      DCs limited tumor metastasis, prolonged survival, and provided curative outcomes
      in ~45% of mice. However, survival was not increased further by additional DC
      treatments or co-transfer of expanded NKT cells. NKT cell activation via
      glycolipid-loaded DCs decreased the frequency and immunosuppressive activity of
      myeloid derived suppressor cells (MDSCs) in tumor-resected mice. In vitro, NKT
      cells were resistant to the immunosuppressive effects of MDSCs and were able to
      reverse the inhibitory effects of MDSCs on T cell proliferation. NKT cell
      activation enhanced antitumor immunity in tumor-resected mice, increasing 4T1
      specific cytotoxic responses and IFNgamma production from natural killer (NK)
      cells and CD8+ T cells. Consistent with increased tumor immunity, mice surviving
      to day 150 were resistant to a second tumor challenge. This work provides a clear
      rationale for manipulating NKT cells to target metastatic disease.

PMID- 25949925
TI  - Discriminative Feature Selection for Uncertain Graph Classification.
AB  - Mining discriminative features for graph data has attracted much attention in
      recent years due to its important role in constructing graph classifiers,
      generating graph indices, etc. Most measurement of interestingness of
      discriminative subgraph features are defined on certain graphs, where the
      structure of graph objects are certain, and the binary edges within each graph
      represent the "presence" of linkages among the nodes. In many real-world
      applications, however, the linkage structure of the graphs is inherently
      uncertain. Therefore, existing measurements of interestingness based upon certain
      graphs are unable to capture the structural uncertainty in these applications
      effectively. In this paper, we study the problem of discriminative subgraph
      feature selection from uncertain graphs. This problem is challenging and
      different from conventional subgraph mining problems because both the structure
      of the graph objects and the discrimination score of each subgraph feature are
      uncertain. To address these challenges, we propose a novel discriminative
      subgraph feature selection method, Dug, which can find discriminative subgraph
      features in uncertain graphs based upon different statistical measures including
      expectation, median, mode and phi-probability. We first compute the probability
      distribution of the discrimination scores for each subgraph feature based on
      dynamic programming. Then a branch-and-bound algorithm is proposed to search for
      discriminative subgraphs efficiently. Extensive experiments on various
      neuroimaging applications (i.e., Alzheimers Disease, ADHD and HIV) have been
      performed to analyze the gain in performance by taking into account structural
      uncertainties in identifying discriminative subgraph features for graph
      classification.

PMID- 25949926
TI  - Practice-Based Research Network Infrastructure Design for Institutional Review
      Board Risk Assessment and Generalizability of Clinical Results.
AB  - Data from clinical studies generated by Practice Based Research Networks should
      be generalizable to the profession. For nationally representative data a broad
      recruitment of practitioners may pose added risks to IRB's. Infrastructure must
      assure data integrity while minimizing risk to assure that the clinical results
      are generalizable. The PEARL Network is an interdisciplinary dental/medical PBRN
      conducting a broad range of clinical studies. The infrastructure is designed to
      support the principles of Good Clinical Practice (GCP) and create a data audit
      trail to ensure data integrity for generalizability. As the PBRN concept becomes
      of greater interest, membership may expand beyond the local community, and the
      issue of geography versus risk management becomes of concern to the IRB. The
      PEARL Network describes how it resolves many of the issues related to recruiting
      on a National basis while maintaining study compliance to ensure patient safety
      and minimize risk to the IRB.

PMID- 25949927
TI  - Advances in Statistical Approaches Oncology Drug Development.
AB  - We describe some recent developments in statistical methodology and practice in
      oncology drug development from an academic and an industry perspective. Many
      adaptive designs were pioneered in oncology, and oncology is still at the
      forefront of novel methods to enable better and faster Go/No-Go decision making
      while controlling the cost.

PMID- 25949928
TI  - Synthesis and evaluation of the antiplasmodial activity of tryptanthrin
      derivatives.
AB  - Malaria remains one of the most deadly diseases threatening humankind and is
      still affecting a significant proportion of the world population, especially in
      Africa. Chemotherapy is a vital component of the fight against the disease and
      new antimalarial agents are urgently needed to curb the spread of malaria
      parasites that are resistant to existing drugs. The natural product tryptanthrin
      is known for its wide range of activities, including antiplasmodial activity, but
      its poor solubility has undermined its development as potent antimicrobial and
      antiprotozoan agent. The aim of this work was to synthesize analogues of
      tryptanthrin and to evaluate their antiplasmodial activity against the asexual
      and sexual blood stages of Plasmodium falciparum. Our results suggest that most
      tryptanthrin analogues retained their antiplasmodial activity against chloroquine
      sensitive and chloroquine-resistant malaria parasites in the nanomolar range (30
      100 nM). The antiplasmodial activity of the most active compound NT1 (IC50: 30
      nM; SI: 155.9) was similar in both strains and close to that of chloroquine
      (IC50: 20 nM) on the sensitive strain. The antiplasmodial activity was improved
      with derivatization, thus pointing out the necessity to explore tryptanthrin
      using medicinal chemistry approaches. Ten (10) of the tested derivatives met the
      criteria, allowing for advancement to animal testing, i.e., SI > 100 and IC50 <
      100 nM. In addition to their activity on the asexual stages, tryptanthrin and two
      selected derivatives (NT1 and T8) prevented the maturation of gametocytes at
      their IC90 concentrations, indicating a transmission-blocking potential.
      Moreover, NT1 was able to impair gametogenesis by reducing the exflagellation of
      microgametes by 20% at IC90, while tryptanthrin and T8 had no influence on
      exflagellation. The results of this study confirm that tryptanthrin and its
      derivatives are potential antimalarial candidates with abilities to kill the
      intraerythrocytic asexual stages and prevent the formation of sexual stages of
      the parasite. 

PMID- 25949929
TI  - Management of patients with a failed kidney transplant: Dialysis reinitiation,
      immunosuppression weaning, and transplantectomy.
AB  - The number of patients reinitiating dialysis after a failed transplant increases
      over time and has more than doubled between the year 1988 and 2010 (an increase
      from 2463 to 5588). More importantly, patients returning to dialysis have been
      shown to have a greater than three-fold increase in the annual adjusted mortality
      rates compared with those with a functioning graft. Continuation of
      immunosuppression to preserve residual graft function has been implicated to be a
      contributing factor, seemingly due to immunosuppression-associated cardiovascular
      and infectious complications and malignancy risk, among others. Nonetheless,
      maintenance low-dose immunosuppression has been suggested to confer survival
      benefit in patients returning to peritoneal dialysis. Whether early vs late
      reinitiation of dialysis or whether transplantectomy has an impact on patient
      survival remains poorly defined. Consensus guidelines for the management of a
      failed allograft are lacking. In this article, we present a literature overview
      on the ideal timing of dialysis reinitiation after graft loss, the management of
      immunosuppression after graft failure, and the risks and benefits of
      transplantectomy. The authors' perspectives on the management of this special
      patient population are also discussed. 

PMID- 25949930
TI  - Novel biomarkers of acute kidney injury: Evaluation and evidence in urologic
      surgery.
AB  - Patients undergoing urologic surgery are at risk of acute kidney injury (AKI) and
      consequently long-term deterioration in renal function. AKI is further associated
      with significantly higher odds of perioperative complications, prolonged hospital
      stay, higher mortality and costs. Therefore, better awareness and detection of
      AKI, as well as identification of AKI determinants in the urological surgery
      setting is warranted to pre-empt and mitigate further deterioration of renal
      function in patients at special risk. New consensus criteria provide precise
      definitions of diagnosis and description of the severity of AKI. However, they
      rely on serum creatinine (SCr), which is known to be an inaccurate marker of
      early changes in renal function. Therefore, several new urinary and serum
      biomarkers promise to address the gap associated with the use of SCr. Novel
      biomarkers may complement SCr measurement or most likely improve the diagnostic
      accuracy of AKI when used in combinations. However, novel biomarkers have to
      prove their clinical applicability, accuracy, and cost effectiveness prior to
      implementation into clinical practice. Most preferably, novel biomarkers should
      help to positively improve a patient's long-term renal functional outcomes. The
      purpose of this review is to discuss currently available biomarkers and to review
      their clinical evidence within urologic surgery settings. 

PMID- 25949932
TI  - Pathogenesis of glomerular haematuria.
AB  - Haematuria was known as a benign hallmark of some glomerular diseases, but over
      the last decade, new evidences pointed its negative implications on kidney
      disease progression. Cytotoxic effects of oxidative stress induced by hemoglobin,
      heme, or iron released from red blood cells may account for the tubular injury
      observed in human biopsy specimens. However, the precise mechanisms responsible
      for haematuria remain unclear. The presence of red blood cells (RBCs) with
      irregular contours and shape in the urine indicates RBCs egression from the
      glomerular capillary into the urinary space. Therefore glomerular haematuria may
      be a marker of glomerular filtration barrier dysfunction or damage. In this
      review we describe some key issues regarding epidemiology and pathogenesis of
      haematuric diseases as well as their renal morphological findings. 

PMID- 25949931
TI  - Complement involvement in kidney diseases: From physiopathology to therapeutical
      targeting.
AB  - Complement cascade is involved in several renal diseases and in renal
      transplantation. The different components of the complement cascade might
      represent an optimal target for innovative therapies. In the first section of the
      paper the authors review the physiopathology of complement involvement in renal
      diseases and transplantation. In some cases this led to a reclassification of
      renal diseases moving from a histopathological to a physiopathological
      classification. The principal issues afforded are: renal diseases with complement
      over activation, renal diseases with complement dysregulation, progression of
      renal diseases and renal transplantation. In the second section the authors
      discuss the several complement components that could represent a therapeutic
      target. Even if only the anti C5 monoclonal antibody is on the market, many
      targets as C1, C3, C5a and C5aR are the object of national or international
      trials. In addition, many molecules proved to be effective in vitro or in
      preclinical trials and are waiting to move to human trials in the future. 

PMID- 25949935
TI  - Impact of obesity on kidney function and blood pressure in children.
AB  - In recent years, obesity has become an increasingly important epidemic health
      problem in children and adolescents. The prevalence of the overweight status in
      children grew from 5% to 11% from 1960s to 1990s. The epidemic of obesity has
      been paralleled by an increase in the incidence of chronic kidney disease (CKD)
      and hypertension. Results of several studies have demonstrated that obesity and
      metabolic syndrome were independent predictors of renal injury. The
      pathophysiology of obesity related hypertension is complex, including activation
      of sympathetic nervous system, renin angiotensin aldosterone system,
      hyperinsulinemia and inflammation. These same mechanisms likely contribute to the
      development of increased blood pressure in children. This review summarizes the
      recent epidemiologic data linking obesity with CKD and hypertension in children,
      as well as the potential mechanisms. 

PMID- 25949933
TI  - Renal dopaminergic system: Pathophysiological implications and clinical
      perspectives.
AB  - Fluid homeostasis, blood pressure and redox balance in the kidney are regulated
      by an intricate interaction between local and systemic anti-natriuretic and
      natriuretic systems. Intrarenal dopamine plays a central role on this interactive
      network. By activating specific receptors, dopamine promotes sodium excretion and
      stimulates anti-oxidant and anti-inflammatory pathways. Different pathological
      scenarios where renal sodium excretion is dysregulated, as in nephrotic syndrome,
      hypertension and renal inflammation, can be associated with impaired action of
      renal dopamine including alteration in biosynthesis, dopamine receptor expression
      and signal transduction. Given its properties on the regulation of renal blood
      flow and sodium excretion, exogenous dopamine has been postulated as a potential
      therapeutic strategy to prevent renal failure in critically ill patients. The aim
      of this review is to update and discuss on the most recent findings about renal
      dopaminergic system and its role in several diseases involving the kidneys and
      the potential use of dopamine as a nephroprotective agent. 

PMID- 25949934
TI  - Oxidative stress as a potential causal factor for autoimmune hemolytic anemia and
      systemic lupus erythematosus.
AB  - The kidneys and the blood system mutually exert influence in maintaining
      homeostasis in the body. Because the kidneys control erythropoiesis by producing
      erythropoietin and by supporting hematopoiesis, anemia is associated with kidney
      diseases. Anemia is the most prevalent genetic disorder, and it is caused by a
      deficiency of glucose 6-phosphate dehydrogenase (G6PD), for which sulfhydryl
      oxidation due to an insufficient supply of NADPH is a likely direct cause.
      Elevated reactive oxygen species (ROS) result in the sulfhydryl oxidation and
      hence are another potential cause for anemia. ROS are elevated in red blood cells
      (RBCs) under superoxide dismutase (SOD1) deficiency in C57BL/6 mice. SOD1
      deficient mice exhibit characteristics similar to autoimmune hemolytic anemia
      (AIHA) and systemic lupus erythematosus (SLE) at the gerontic stage. An
      examination of AIHA-prone New Zealand Black (NZB) mice, which have normal SOD1
      and G6PD genes, indicated that ROS levels in RBCs are originally high and further
      elevated during aging. Transgenic overexpression of human SOD1 in erythroid cells
      effectively suppresses ROS elevation and ameliorates AIHA symptoms such as
      elevated anti-RBC antibodies and premature death in NZB mice. These results
      support the hypothesis that names oxidative stress as a risk factor for AIHA and
      other autoimmune diseases such as SLE. Herein we discuss the association between
      oxidative stress and SLE pathogenesis based mainly on the genetic and phenotypic
      characteristics of NZB and New Zealand white mice and provide insight into the
      mechanism of SLE pathogenesis. 

PMID- 25949936
TI  - Strategies to optimize shock wave lithotripsy outcome: Patient selection and
      treatment parameters.
AB  - Shock wave lithotripsy (SWL) was introduced in 1980, modernizing the treatment of
      upper urinary tract stones, and quickly became the most commonly utilized
      technique to treat kidney stones. Over the past 5-10 years, however, use of SWL
      has been declining because it is not as reliably effective as more modern
      technology. SWL success rates vary considerably and there is abundant literature
      predicting outcome based on patient- and stone-specific parameters. Herein we
      discuss the ways to optimize SWL outcomes by reviewing proper patient selection
      utilizing stone characteristics and patient features. Stone size, number,
      location, density, composition, and patient body habitus and renal anatomy are
      all discussed. We also review the technical parameters during SWL that can be
      controlled to improve results further, including type of anesthesia, coupling,
      shock wave rate, focal zones, pressures, and active monitoring. Following these
      basic principles and selection criteria will help maximize success rate. 

PMID- 25949938
TI  - Treatment of hypogonadotropic male hypogonadism: Case-based scenarios.
AB  - The aim of this study is to review four case-based scenarios regarding the
      treatment of symptomatic hypogonadism in men. The article is designed as a review
      of published literature. We conducted a PubMed literature search for the time
      period of 1989-2014, concentrating on 26 studies investigating the efficacy of
      various therapeutic options on semen analysis, pregnancy outcomes, time to
      recovery of spermatogenesis, as well as serum and intratesticular testosterone
      levels. Our results demonstrated that exogenous testosterone suppresses
      intratesticular testosterone production, which is an absolute prerequisite for
      normal spermatogenesis. Cessation of exogenous testosterone should be recommended
      for men desiring to maintain their fertility. Therapies that protect the testis
      involve human chorionic gonadotropin (hCG) therapy or selective estrogen receptor
      modulators (SERMs), but may also include low dose hCG with exogenous
      testosterone. Off-label use of SERMs, such as clomiphene citrate, are effective
      for maintaining testosterone production long-term and offer the convenience of
      representing a safe, oral therapy. At present, routine use of aromatase
      inhibitors is not recommended based on a lack of long-term data. We concluded
      that exogenous testosterone supplementation decreases sperm production. It was
      determined that clomiphene citrate is a safe and effective therapy for men who
      desire to maintain fertility. Although less frequently used in the general
      population, hCG therapy with or without testosterone supplementation represents
      an alternative treatment. 

PMID- 25949939
TI  - Is there a role for systemic targeted therapy after surgical treatment for
      metastases of renal cell carcinoma?
AB  - Metastatic renal cell carcinoma (mRCC) is a challenging disease. Despite the new
      targeted therapies, complete remissions occur only in 1%-3% of the cases, and the
      most effective first-line treatment drugs have reached a ceiling in overall
      survival (ranging from 9 to 49 mo). Metastasectomy remains to be the only
      curative option in most patients with mRCC. Prognostic nomograms have been
      recently published, so we have tools to classify patients in risk groups,
      allowing us to detect the cases with the higher risk of recurrence after
      metastasectomy. Although sparse, there is some evidence of effectiveness of
      neoadjuvant targeted therapy before metastasectomy; but with an increase in
      surgical complications due to the effects of these new drugs in tissue healing.
      We have aimed to answer the question: Is there a role for systemic targeted
      therapy after surgical treatment for metastases of renal cell carcinoma? We have
      made a search in Pubmed database. As far as we know, evidence is low and it's
      based in case reports and small series of patients treated with adjuvant drugs
      after neoadjuvant therapy plus metastasectomy in cases of partial response to
      initial systemic treatment. Despite the limitations and high risk of bias,
      promising results and cases with long-term survival with this approach have been
      described. Two ongoing clinical trials may answer the question that concerns us. 

PMID- 25949937
TI  - Primary and secondary hyperoxaluria: Understanding the enigma.
AB  - Hyperoxaluria is characterized by an increased urinary excretion of oxalate.
      Primary and secondary hyperoxaluria are two distinct clinical expressions of
      hyperoxaluria. Primary hyperoxaluria is an inherited error of metabolism due to
      defective enzyme activity. In contrast, secondary hyperoxaluria is caused by
      increased dietary ingestion of oxalate, precursors of oxalate or alteration in
      intestinal microflora. The disease spectrum extends from recurrent kidney stones,
      nephrocalcinosis and urinary tract infections to chronic kidney disease and end
      stage renal disease. When calcium oxalate burden exceeds the renal excretory
      ability, calcium oxalate starts to deposit in various organ systems in a process
      called systemic oxalosis. Increased urinary oxalate levels help to make the
      diagnosis while plasma oxalate levels are likely to be more accurate when
      patients develop chronic kidney disease. Definitive diagnosis of primary
      hyperoxaluria is achieved by genetic studies and if genetic studies prove
      inconclusive, liver biopsy is undertaken to establish diagnosis. Diagnostic clues
      pointing towards secondary hyperoxaluria are a supportive dietary history and
      tests to detect increased intestinal absorption of oxalate. Conservative
      treatment for both types of hyperoxaluria includes vigorous hydration and
      crystallization inhibitors to decrease calcium oxalate precipitation. Pyridoxine
      is also found to be helpful in approximately 30% patients with primary
      hyperoxaluria type 1. Liver-kidney and isolated kidney transplantation are the
      treatment of choice in primary hyperoxaluria type 1 and type 2 respectively. Data
      is scarce on role of transplantation in primary hyperoxaluria type 3 where there
      are no reports of end stage renal disease so far. There are ongoing
      investigations into newer modalities of diagnosis and treatment of hyperoxaluria.
      Clinical differentiation between primary and secondary hyperoxaluria and further
      between the types of primary hyperoxaluria is very important because of
      implications in treatment and diagnosis. Hyperoxaluria continues to be a
      challenging disease and a high index of clinical suspicion is often the first
      step on the path to accurate diagnosis and management. 

PMID- 25949940
TI  - Primary glomerular diseases in the elderly.
AB  - Primary glomerular diseases in the elderly population are a frustrating topic due
      to difficulties in both the diagnosis and decision making about treatment. The
      most frequent type of primary glomerular disease in elderly is membranous
      nephropathy; while its counterpart in younger population is IgA nephropathy. The
      most frequent cause of nephrotic syndrome in the elderly is also membranous
      nephropathy. Pauci-immune crescentic glomerulonephritis (GN) rate increases both
      in elderly and very elderly population. Pauci-immune crescentic GNs should be
      regarded as urgencies in elderly patients as in their younger counterparts due to
      potential for causing end-stage renal disease in case of delayed diagnosis and
      treatment, and also causing mortality due to alveolar hemorrhage in patients with
      pulmonary involvement. Renal biopsy is the inevitable diagnostic method in the
      elderly as in all other age groups. Renal biopsy prevents unnecessary treatments
      and provides prognostic data. So advanced age should not be the sole
      contraindication for renal biopsy. The course of primary glomerular diseases may
      differ in the elderly population. Acute kidney injury is more frequent in the
      course and renal functions may be worse at presentation. These patients are more
      prone to be hypertensive. The decision about adding immune suppressive therapies
      to conservative methods should be made considering many factors like co
      morbidities, drug side effects and potential drug interactions, risk of
      infection, patient preference, life expectancy and renal functions at the time of
      diagnosis. 

PMID- 25949941
TI  - Effect of urinary stone disease and its treatment on renal function.
AB  - Urolithiasis is a common disease that affects urinary tract in all age groups.
      Both in adults and in children, stone size, location, renal anatomy, and other
      factors, can influence the success of treatment modalities. Recently, there has
      been a great advancement in technology for minimally invasive management of
      urinary stones. The epoch of open treatment modalities has passed and currently
      there are much less invasive treatment approaches, such as percutaneous
      nephrolithotomy, ureteroscopy, shockwave lithotripsy, and retrograde internal
      Surgery. Furthermore, advancement in imaging technics ensures substantial
      knowledge that permit physician to decide the most convenient treatment method
      for the patient. Thus, effective and rapid treatment of urinary tract stones is
      substantial for the preservation of the renal function. In this review, the
      effects of the treatment options for urinary stones on renal function have been
      reviewed.

PMID- 25949942
TI  - Management of hepatorenal syndrome.
AB  - Hepatorenal syndrome (HRS) is defined as development of renal dysfunction in
      patients with chronic liver diseases due to decreased effective arterial blood
      volume. It is the most severe complication of cirrhosis because of its very poor
      prognosis. In spite of several hypotheses and research, the pathogenesis of HRS
      is still poorly understood. The onset of HRS is a progressive process rather than
      a suddenly arising phenomenon. Since there are no specific tests for HRS
      diagnosis, it is diagnosed by the exclusion of other causes of acute kidney
      injury in cirrhotic patients. There are two types of HRS with different
      characteristics and prognostics. Type 1 HRS is characterized by a sudden onset
      acute renal failure and a rapid deterioration of other organ functions. It may
      develop spontaneously or be due to some precipitating factors. Type 2 HRS is
      characterized by slow and progressive worsening of renal functions due to
      cirrhosis and portal hypertension and it is accompanied by refractory ascites.
      The only definitive treatment for both Type 1 and Type 2 HRS is liver
      transplantation. The most suitable bridge treatment or treatment for patients who
      are not eligible for transplantation is a combination of terlipressin and
      albumin. For the same purpose, it is possible to try hemodialysis or renal
      replacement therapies in the form of continuous veno-venous hemofiltration.
      Artificial hepatic support systems are important for patients who do not respond
      to medical treatment. Transjugular intrahepatic portosystemic shunt may be
      considered as a treatment modality for unresponsive patients to medical
      treatment. The main goal of clinical surveillance in a cirrhotic patient is
      prevention of HRS before it develops. The aim of this article is to provide an
      updated review about the physiopathology of HRS and its treatment. 

PMID- 25949943
TI  - Evidence-based medicine: An update on treatments for peritoneal dialysis-related
      peritonitis.
AB  - Peritonitis continues to be a major complication of peritoneal dialysis (PD), and
      adequate treatment is crucial for a favorable outcome. There is no consensus
      regarding the optimal therapeutic regimen, and few prospective controlled studies
      have been published. The objective of this manuscript is to review the results of
      PD peritonitis treatment reported in narrative reviews, systematic reviews, and
      proportional meta-analyses. Two narrative reviews, the only existing systematic
      review and its update published between 1991 and 2014 were included. In addition,
      we reported the results of a proportional meta-analysis published by our group.
      Results from systematic reviews of randomized control trials (RCT) and quasi-RCT
      were not able to identify any optimal antimicrobial treatment, but glycopeptide
      regimens were more likely to achieve a complete cure than a first generation
      cephalosporin. Compared to urokinase, simultaneous catheter removal and
      replacement resulted in better outcomes. Continuous and intermittent IP
      antibiotic use had similar outcomes. Intraperitoneal antibiotics were superior to
      intravenous antibiotics in reducing treatment failure. In the proportional meta
      analysis of RCTs and the case series, the resolution rate (86%) of ceftazidime
      plus glycopeptide as initial treatment was significantly higher than first
      generation cephalosporin plus aminoglycosides (66%) and glycopeptides plus
      aminoglycosides (75%). Other comparisons of regimens used for either initial
      treatment or treatment of gram-positive rods or gram-negative rods did not show
      statistically significant differences. The superiority of a combination of a
      glycopeptide and a third generation cephalosporin was also reported by a
      narrative review study published in 1991, which reported an 88% resolution rate. 

PMID- 25949944
TI  - African origins and chronic kidney disease susceptibility in the human
      immunodeficiency virus era.
AB  - Chronic kidney disease (CKD) is a major public health problem worldwide with the
      estimated incidence growing by approximately 6% annually. There are striking
      ethnic differences in the prevalence of CKD such that, in the United States,
      African Americans have the highest prevalence of CKD, four times the incidence of
      end stage renal disease when compared to Americans of European ancestry
      suggestive of genetic predisposition. Diabetes mellitus, hypertension and human
      immunodeficiency virus (HIV) infection are the major causes of CKD. HIV
      associated nephropathy (HIVAN) is an irreversible form of CKD with considerable
      morbidity and mortality and is present predominantly in people of African
      ancestry. The APOL1 G1 and G2 alleles were more strongly associated with the risk
      for CKD than the previously examined MYH9 E1 risk haplotype in individuals of
      African ancestry. A strong association was reported in HIVAN, suggesting that 50%
      of African Americans with two APOL1 risk alleles, if untreated, would develop
      HIVAN. However these two variants are not enough to cause disease. The prevailing
      belief is that modifying factors or second hits (including genetic hits) underlie
      the pathogenesis of kidney disease. This work reviews the history of genetic
      susceptibility of CKD and outlines current theories regarding the role for APOL1
      in CKD in the HIV era. 

PMID- 25949945
TI  - Species differences in regulation of renal proximal tubule transport by certain
      molecules.
AB  - Renal proximal tubules (PTs) play important roles in the regulation of acid/base,
      plasma volume and blood pressure. Recent studies suggest that there are
      substantial species differences in the regulation of PT transport. For example,
      thiazolidinediones (TZDs) are widely used for the treatment of type 2 diabetes
      mellitus, but the use of TZDs is associated with fluid overload. In addition to
      the transcriptional enhancement of sodium transport in distal nephrons, TZDs
      rapidly stimulate PT sodium transport via a non-genomic mechanism depending on
      peroxisome proliferator activated receptor gamma/Src/epidermal growth factor
      receptor (EGFR)/MEK/ERK. In mouse PTs, however, TZDs fail to stimulate PT
      transport probably due to constitutive activation of Src/EGFR/ERK pathway. This
      unique activation of Src/ERK may also affect the effect of high concentrations of
      insulin on mouse PT transport. On the other hand, the effect of angiotensin II
      (Ang II) on PT transport is known to be biphasic in rabbits, rats, and mice.
      However, Ang II induces a concentration-dependent, monophasic transport
      stimulation in human PTs. The contrasting responses to nitric oxide/guanosine
      3',5'-cyclic monophosphate pathway may largely explain these different effects of
      Ang II on PT transport. In this review, we focus on the recent findings on the
      species differences in the regulation of PT transport, which may help understand
      the species-specific mechanisms underlying edema formation and/or hypertension
      occurrence. 

PMID- 25949946
TI  - Histopathology of renal asphyxia in newborn piglets: Individual susceptibility to
      tubular changes.
AB  - AIM: To analyze the effects on the kidney of hypoxia-reoxygenation in an
      experimental model of normocapnic asphyxia. METHODS: To this end, 40 newborn
      Landrace/Large-White piglets aged 1-4 d were studied in this work. Hypoxia was
      induced by decreasing the inspired fiO2 to 0.06-0.08. Animals were resuscitated
      with different fiO2 and subdivided into 4 groups: group 1, 2, 3 and 4 received
      18%, 21%, 40% and 100% O2 respectively. Macroscopic examination was carried out
      to evidence possible pathological features. Tissue sample were obtained from both
      kidneys. Four or five micron paraffin sections were stained with H-E and PAS
      stain and examined under an optical microscope. RESULTS: Pathological changes,
      mainly affecting tubular cells, were observed in the vast majority of kidneys of
      asphyxiated piglets. The most frequent tubular changes were: tubular casts (95%),
      tubular dilatation (87.5%), tubular vacuolization (70%), tubular eosinophilia
      (52.5%), sloughing (50%), fragmentation of the brush border (50%), oedema
      (32.5%), apoptosis (15%) and glomerular changes (meningeal cell proliferation,
      capsular adhesion between the flocculus and Bowman's capsule, glomerulosclerosis
      and fibrous or cellular crescents associated with collapse of the glomerular
      tuft). Statistical analysis was carried out on changes observed when the animals
      were allocated in the 4 groups (chi(2)-test 0.05). The statistical analysis
      showed no evidence of differences regarding kidney lesions among the animals
      groups. CONCLUSION: Our data show that renal pathology in newborn piglets is
      characterized by interindividual variability to hypoxia and is not associated
      with oxygen concentration.

PMID- 25949947
TI  - Prolonged hypernatremia triggered by hyperglycemic hyperosmolar state with coma:
      A case report.
AB  - A man with past lithium use for more than 15 years, but off lithium for two years
      and not carrying the diagnosis of diabetes mellitus or nephrogenic diabetes
      insipidus (NDI), presented with coma and hyperglycemic hyperosmolar state (HHS).
      Following correction of HHS, he developed persistent hypernatremia accompanied by
      large volumes of urine with low osmolality and no response to desmopressin
      injections. Urine osmolality remained < 300 mOsm/kg after injection of
      vasopressin. Improvement in serum sodium concentration followed the intake of
      large volumes of water plus administration of amiloride and hydrochlorothiazide.
      Severe hyperglycemia may trigger symptomatic lithium-induced NDI years after
      cessation of lithium therapy. Patients with new-onset diabetes mellitus who had
      been on prolonged lithium therapy in the past require monitoring of their serum
      sodium concentration after hyperglycemic episodes regardless of whether they do
      or do not carry the diagnosis of NDI. 

PMID- 25949948
TI  - The effect of hydro-alcoholic extract of Artemisia absinthium on appetite in male
      rats.
AB  - OBJECTIVES: weight loss as a consecution of losing appetite in post-operative
      patients and those suffering from HIV, cancer, cachexia and inflammatory diseases
      are the main inducements of morbidity and mortality. There is an increasing
      demand for more efficacious and endurable appetite stimulating treatment for
      patients with cachexia. Health economics is influenced by the malnutrition which
      was accounted for 5% of Iranian populations in 2011. Artemisia absinthium is
      known as an orexigenic herb in Iranian traditional medicine. Little evidence is
      available about its orexigenic effect and mechanism. So, the present study
      evaluated the possible effect on appetite of hydroalcoholic extract of Artemisia
      absinthium . MATERIALS AND METHODS: Thirty male Wistar rats were randomly divided
      into five groups. Vehicle group received 0.5 ml water per day, control group did
      not receive anything and other 3 groups received 50, 100 and 150 mg/kg of
      Artemisia absinthium for 7 days respectively. The daily amount of the food eaten
      by each rat was measured for 10 consecutive days. The amount of energy intake for
      each rat was also calculated for 7 days during the intervention. The difference
      in energy intake was calculated and compared between groups. RESULTS: The results
      suggest that there was no significant (p>0.05) differences in energy received
      before and during intervention between three case groups compared with the
      control group. The energy intake in 1-2 hours after extract injection in all
      groups, and energy intake after 24 hours interval in third case group (receiving
      150 mg/kg extract) is higher compared to other intervals, but it is not
      significant (p>0.05). So, it can be stated that there was no significant
      differences between energy intake of 3 case groups and control group. CONCLUSION:
      Artemisia absinthium had no positive and dose-related effects on appetite of
      rats. Future studies are needed to evaluate the orexigenic effect of this plant.

PMID- 25949949
TI  - Cancer therapy with phytochemicals: evidence from clinical studies.
AB  - Cancer is still one of the major causes of mortality in both developing and
      developed countries. At present, in spite of intensive interventions, a large
      number of patients suffer from poor prognosis. Therefore, the effort for finding
      new anticancer agents with better efficacy and lesser side effects has been
      continued. According to the traditional recommendations and experimental studies,
      numerous medicinal plants have been reported to have anticancer effect. Also
      antiproliferative, pro-apoptotic, anti-metastatic and anti-angiogenic effects of
      several phytochemicals have been shown in in vitro experiments or animal studies.
      However, only a small number have been tested in cancerous patients and limited
      evidence exists for their clinical effectiveness. Also, regarding some
      phytochemicals, only beneficial effects on cancer-related symptoms or on quality
      of life have been reported and no positive results exist for their antitumor
      actions. This review was focused on the phytochemicals whole beneficial effects
      on various types of cancer have been supported by clinical trials. Based on the
      literature review, curcumin, green tea, resveratrol and Viscum album were the
      satisfactory instances of clinical evidence for supporting their anticancer
      effects. The main findings of these phytochemicals were also summarized and
      discussed. 

PMID- 25949950
TI  - In Vitro antibacterial and in Vivo cytotoxic activities of Grewia paniculata.
AB  - OBJECTIVES: Grewia paniculata (Family: Malvaceae) has been used to treat
      inflammation, respiratory disorders and fever. It is additionally employed for
      other health conditions including colds, diarrhea and as an insecticide in
      Bangladesh. The aim of the present study was to investigate the antibacterial and
      cytotoxic activities of different extracts of Grewia paniculata. MATERIALS AND
      METHODS: The antibacterial activity was evaluated against both gram negative and
      gram positive bacteria using disc diffusion method by determination of the
      diameter of zone of inhibition. Cytotoxic activity was performed by brine shrimp
      (Artemia salina) lethality bioassay. RESULTS: In disc diffusion method, all the
      natural products (400 MUg/disc) showed moderate to potent activity against all
      the tested bacteria. The ethanol extract of bark (EEB) and ethanol fraction of
      bark (EFB) (400 MUg/disc) exhibited highest activity against Shigella dysenteriae
      with a zone of inhibition of 23+/-1.63 mm and 23+/-1.77 mm respectively. In the
      brine shrimp lethality bioassay all the extracts showed moderate cytotoxic
      activity when compared with the standard drug vincristin sulphate. For example,
      LC50 value of the ethanol fraction of bark (EFB) was 3.01 MUg/ml while the LC50
      of vincristine sulphate was 0.52 MUg/ml. CONCLUSIONS: The results suggest that
      all the natural products possess potent antibacterial and moderate cytotoxic.

PMID- 25949951
TI  - Evaluation of the antibacterial activity of the Althaea officinalis L. leaf
      extract and its wound healing potency in the rat model of excision wound
      creation.
AB  - OBJECTIVES: Wound is defined simply as the disruption of the biochemical,
      cellular, and anatomic continuity of a tissue. Plants and their extracts known as
      phytomedicine have immense potential for the management and treatment of wounds.
      MATERIALS AND METHODS: Due to the undesirable side effects, in the control and
      treatment of the wound infections, it is recommended to use natural materials
      such as phytochemicals instead of chemically synthesized drugs. Thus, the aim of
      this research was to study the anti-microbial and wound healing potential of
      Althaea officinalis L. hydroalchoholic extract in comparison with ciprofloxacin,
      gentamicin, and penicillin antibiotics on clinical strains as well as pathogenic
      bacteria such as Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus,
      and Listeria monocytogenes under in vitro conditions using micro broth dilution
      and disc diffusion methods. Moreover, MIC and MBC of its hydroalchoholic extract
      was also evaluated. RESULTS: The results showed that although Althaea officinalis
      L. extract was not effective on gram-negative bacteria but it was efficacious on
      gram-positive bacteria. The extract was also tested in the form of topical
      administration on excision wound model in rats. In the extract-treated wounds,
      the wound healing percent was significantly increased in comparison with
      controls. CONCLUSIONS: Based on this research, herbal extract of officinalis L.
      can be a great candidate for the treatment of gram-positive infections and merits
      further studies.

PMID- 25949952
TI  - Effects of aqueous extract of celery (Apium graveolens L.) leaves on
      spermatogenesis in healthy male rats.
AB  - OBJECTIVES: Nowadays, a lot of attention has been paid to the therapeutic
      properties of herbs, including evaluation of the effects of these plants on
      fertility in laboratory animals. Apium graveolens L. (celery) has been widely
      used in traditional medicine for treatment of various disorders including
      impotency. Therefore, this study was designed to investigate the effects of
      aqueous extract of A. graveolens on testicular tissue and spermatogenesis in
      healthy male rats. MATERIALS AND METHODS: In this research, 24 apparently healthy
      male rats were divided into three groups, including eight rats in each. The first
      group as control received only distilled water 1 ml/animal/day. The second and
      third groups orally received 100 and 200 mg/kg b.w. of the extract, respectively,
      for 30 days. The day after the last administration of the extract, the rats were
      sacrificed, the testes were removed entirely, and the morphometric studies were
      carried out. Epididymal sperm count and histological studies of testicular tissue
      were conducted. RESULTS: The comparison between the treated and control groups
      revealed a remarkable increase in the seminiferous tubules diameter, testes
      volume (p<=0.001), and the number of spermatogonia, primary spermatocytes and
      spermatozoa. Furthermore, the increase in the number of spermatids and epididymal
      weight were only significant at high doses of the extract (p<= 0.05).
      CONCLUSIONS: The results from this study indicated that administration of celery
      leaf extract may improve spermatogenesis process and also be useful for some
      sperm fertility parameters.

PMID- 25949953
TI  - Ellagic acid improved arrhythmias induced by CaCL2 in the rat stress model.
AB  - OBJECTIVE: In ventricular arrhythmias, due to their free radical scavenging
      action, antioxidant agents are usually used in the treatment of cardiovascular
      disease. Since stress is considered as risk factor for increased mortality by
      causing malignant arrhythmias, the study was designed to evaluate the
      cardioprotective effects of ellagic acid (EA) on CaCl2-induced arrhythmias in rat
      stress model. MATERIALS AND METHODS: Male Sprague-Dawley rats (200-250 g) were
      divided into four groups: Group I: Control rats (2 ml of saline by gavage), Group
      II: Rats treated with EA (15 mg/kg, gavage), Group III: stress group, Group IV:
      received EA plus stress. Stress was applied in a restrainer box (6 hour/day, 21
      days). After induction of anesthesia, lead II electrocardiogram was recorded for
      calculating heart rate and QRS complex. The arrhythmia was produced by injection
      of CaCl2 solution (140 mg/kg, iv) and incidences of Ventricular fibrillation,
      Ventricular premature beats and Ventricular tachycardia were recorded. Results
      were analyzed by using one-way ANOVA and Fisher's exact test. p<0.05 was
      considered as significant level. RESULTS: The results showed a positive inotropic
      effect and negative chronotropic effect for the EA group in comparison with the
      control group. Incidence rates (%) of premature beats, ventricular fibrillation
      and ventricular tachycardia in stress group and all the arrhythmia parameters
      decreased in groups which received EA. CONCLUSIONS: By decreasing the incidence
      rates of premature beats, fibrillation and ventricular tachycardia in groups
      which received EA, ellagic acid probably acted as an anti-arrhythmic agent which
      showed to have aprotective functionin heart.

PMID- 25949954
TI  - Antidiarrheal activity and acute oral toxicity of Mentha longifolia L. essential
      oil.
AB  - OBJECTIVES: Mentha longifolia L. (Lamiaceae) is an annual herb that is used in
      the Iranian traditional medicine for treating stomach and intestinal disorders.
      The purpose of this study was to determine the protective effect of M. longifolia
      on experimental diarrhea in a rat model. MATERIALS AND METHODS: The antidiarrheal
      activity of essential oil of M. longifolia (20-80 mg/kg) was investigated against
      castor oil-induced diarrhea in rats using loperamide as the standard reference
      drug. In acute toxicity evaluation, rats were orally administrated with single
      dose of EOML at doses ranging from 10 to 1000 mg/kg. RESULTS: EOML caused a
      significant (p<0.05) and dose-dependent decrease of gastrointestinal transit,
      nevertheless, it could not block the inhibitory effect of atropine (0.1 mg/kg).
      EOML at oral doses of 20 and 80 mg/kg protected the animals against castor oil
      induced diarrhea significantly (p<0.05). EOML decreased the intestinal fluid
      accumulation as indicated by the significantly (p<0.05 to p<0.001) decrease
      compared to control. The oral LD50 of EOML was found to be 470 mg/kg in rat.
      CONCLUSION: Since the inhibition of intestinal hyperactivity and hypersecretory
      are the bases of the treatment of diarrhea, results obtained in the present study
      suggest that EOML is endowed with antidiarrheal activity. EOML is moderately
      toxic for oral medication.

PMID- 25949955
TI  - Effects of ethanol extract of Salvia hydrangea on hepatic and renal functions of
      streptozotocin-induced diabetic rats.
AB  - OBJECTIVES: A wide range of liver and kidney disorders are associated with
      diabetes and there is a mutual relationship between diabetes and these diseases.
      Herbal medicine with having abundant ingredients is one of these options. The
      goal of this study was to compare the effects of alcoholic extract of aerial
      parts of S alvia hydrangea with glibenclamide on functional tests of liver and
      kidney in diabetic rats induced by streptozotocin. MATERIALS AND METHODS: In this
      study, 35 male Wistar rats were divided into five groups (n= 7 in each group):
      control, diabetic control, and three experimental diabetic groups. The controls
      had normal access to water and food, the diabetic control group was given drug
      solvent and the three experimental groups received ethanol extract of Salvia
      hydrangea at doses of 100 and 200 mg and glibenclamideat a dose of 10 mg/kg/BW by
      gavage, respectively. To induce diabetes, a single dose of streptozotocin (60
      mg/kg/BW) was injected to rats intraperitoneally. Blood samples were collected at
      day 21 from all groups and the related blood factors were measured and analyzed.
      RESULTS: The results showed that the levels of creatinine, urea, aspartate
      aminotransferase (AST), and fasting blood sugar (FBS) in all diabetic groups
      increased compared to the control group. In all experimental groups and the group
      which received glibenclamide,a significant decrease was shown compared to the
      diabetic group (p<0.05). CONCLUSION: The consumption of alcoholic extract of
      aerial parts of Salvia hydrangea may have beneficial effects on the reduction of
      diabetic complications by lowering blood sugar without any adverse effects on the
      kidney and liver tissue.

PMID- 25949956
TI  - Effects of aqueous extract of turnip leaf (Brassica rapa) in alloxan-induced
      diabetic rats.
AB  - OBJECTIVES: Turnip leaf has been used in folk medicine of Iran for the treatment
      of diabetes. However,so far no scientific study has been done to support its use
      in traditional medicine. The present study was carried out to evaluate the
      possible hypoglycemic efficacy of aqueous extract of turnip leaf (AETL) in
      diabetic rats. MATERIALS AND METHODS: Alloxan-induced diabetic rats were orally
      treated with AETL at doses of 200 and 400 mg/kg body weight (bw) per day for 28
      days. In order to evaluate the anti-diabetic activity, fasting blood glucose
      concentrations were determined on the 1(st), 14(th) and 29(th) days. Moreover,at
      the end of the study, plasma concentrations of total cholesterol, triglyceride
      (TG), high density lipoprotein cholesterol (HDL-c), low density lipoprotein
      cholesterol (LDL-c), aspartate amino transfarase (AST), and alanine amino
      transferase (ALT) were measured by the use of standard kits and auto-analyzer.
      RESULTS: Both doses of AETL significantly decreased (p<0.001) blood glucose and
      ALT levels in diabetic rats after 28 days of administration. AETL at both doses
      decreased (p<0.05) plasma total cholesterol and LDL-c in diabetic rats, but they
      significantly decreased (p<0.05) HDL-c and increased triglycerideand AST levels
      in a-dose dependent manner. CONCLUSION: The results showed that AETL has a dose-
      dependent decrease in the blood glucose in diabetic rats. However,we should not
      be unaware of adverse effects of AETL on lipid profiles and liver enzymes
      activity, especially decrease of HDL and increase of TG and AST.

PMID- 25949957
TI  - Cytoprotective and antioxidant effects of Echium amoenum anthocyanin-rich extract
      in human endothelial cells (HUVECs).
AB  - OBJECTIVE: Echium amoenum Fisch. & C.A. Mey. is used for the treatment of various
      diseases in traditional medicine. This plant is a major source of anthocyanins
      with beneficial cardiovascular properties such as anti-atherosclerotic and
      antihypertensive effects. In the present study, the protective and antioxidant
      effects of anthocyanin-rich E. amoenum extract were evaluated on human vascular
      endothelial cells (HUVECs) under oxidative stress. MATERIALS AND METHODS: Cell
      viability and oxidative status were assessed on H2O2-induced oxidative stress
      (0.5 mM H2O2 for 2 h) in HUVECs pretreated by anthocyanin-rich extract from the
      petals of E. amoenum (25-1000 ug/ml). Cytoprotective effect of the extract was
      evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
      assay. The hydroperoxides concentration and ferric reducing antioxidant power
      (FRAP) were assessed in intra- and extra-cellular fluid of pretreated cells.
      RESULTS: Pretreatment of HUVECs with E. amoenum extract at the concentrations of
      100-1000 ug/ml reduced the cell death resulted from the exposure to H2O2 in a
      concentration-dependent manner. E. amoenum extract decreased hydroperoxides
      concentration and increased FRAP value in both intra- and extra-cellular fluid at
      different concentration ranges. Moreover, it did not show cytotoxic effects at
      the concentration range of 25-1000 ug/ml. CONCLUSION: These results suggest
      antioxidant and protective effect of anthocyanin-rich extract of the petals of E.
      amoenum against H2O2-induced oxidative stress in HUVECs. However, further
      investigations are needed for understanding the detailed mechanisms of
      cytoprotective effects of this traditional herbal medicine.

PMID- 25949958
TI  - The leadership crisis of medical profession in India: ongoing impact on the
      health system.
AB  - By 2030 India will have one million additional MBBS doctors; currently being
      produced @50,000 per year. Contrary to perception of scarcity of medical doctors,
      a large section of newly qualified physicians are spending considerable years in
      dysfunctional status due to mismanagement in human resource in health in India.
      There are very few employment opportunities for qualified doctors in public
      sector; at the same time the average salary of MBBS doctors in urban private
      hospitals is very low. Paradoxically, in a country of 1.3 billion populations
      there is no actual demand for medical professionals. While the popular perception
      is that young doctors are not willing for community service, a reality check is
      required on the count of intent and capacity of public sector as well as industry
      towards engagement of medical doctors in the process of service delivery. The
      visible leaders of medical profession are unable to reflect the ground reality.
      There is a leadership crisis among medical doctors in India. 

PMID- 25949959
TI  - Master's and doctoral theses in family medicine and their publication output,
      Suez Canal University, Egypt.
AB  - BACKGROUND: The completion of a thesis is a significant requirement for both a
      Master's and a doctorate degree in general practice/family medicine (GP/FM). A
      postgraduate thesis is a well-planned, time-intensive activity carried out over
      several years. The quality of the theses can be judged by the proportion of
      published papers. OBJECTIVE: This study aimed to describe Master's and doctoral
      theses in family medicine and their publications between 1982 and 2014. MATERIALS
      AND METHODS: GP/FM degree theses were reviewed at the Faculty of Medicine and
      central Suez Canal libraries. Several characteristics were extracted from each
      thesis relating to the main researcher, supervisors, themes, and study methods
      according to predefined criteria. Publications from the theses were described.
      RESULTS: Over 33 years, 208 theses were completed by 173 GP/FM researchers. The
      majority of the theses were for Master's degrees (84.1%). Regarding the study
      design, most of the degree theses were cross-sectional studies (76.9%). The adult
      population was targeted in 33.7% of research theses. Nonprobability sampling was
      used in 51%. Rural communities were the setting of research in 43.8%, and primary
      health center (PHC)-based studies in 59.1%. The "Patient" category exceeded the
      other categories (28.4%). Publication from theses started in the second decade of
      research production. Of the degree theses, 21.6% original articles were
      published. Only 13.3% of articles from theses were published in PubMed-indexed
      journals. The researcher was first author in 62.2% of published articles.
      CONCLUSION: The production of GP/FM theses and their publications are going to
      increase. Continuous assessment and planning for GP/FM studies are recommended.

PMID- 25949960
TI  - Training medical students in general practice: a qualitative study among general
      practitioner trainers in Sri Lanka.
AB  - INTRODUCTION: Worldwide Family Medicine has gained an important place in the
      undergraduate medical curriculum over the last few decades and general practices
      have become training centers for students. Exposure to patients early in the
      disease process, out patient management of common problems, follow up of chronic
      diseases and psychosocial aspects of health and disease are educational
      advantages of community based training but such training could have varying
      impact on patients, students and trainers. This study explored the views of
      General Practitioner (GP) trainers on their experience in training students.
      METHODOLOGY: This qualitative study was conducted among GP trainers of the
      faculty of medicine, University of Kelaniya, Sri Lanka, to explore their
      experience on wide range of issues related to their role as GP trainers. The
      interviews were recorded and transcribed verbatim. Themes expressed were
      identified. RESULTS: Altruistic reasons, self-satisfaction, self-esteem and
      opportunity to improve their knowledge were the motivations for their involvement
      in teaching. Teachers were confident of their clinical and teaching skills. They
      perceived that patients were willing participants of the process and benefited
      from it. There was a positive impact on consultation dynamics. Time pressure was
      the major problem and ideal number of trainees per session was two. They were
      willing to attend teacher training workshops to update their knowledge.
      CONCLUSIONS: GP trainers driven by altruistic reasons were willing participants
      of student training process. The perceived advantages of involvement of teaching
      for trainers and patients were an encouragement for potential trainers.
      University should organize training sessions for trainers which will boost their
      knowledge, confidence and teaching skills which will eventually benefit students.

PMID- 25949961
TI  - Misplaced priorities in the Union Health Budget 2015.
AB  - The Union Budget presented on 28 February 2015 in the Indian parliament has
      allocated only INR 33,000 crores for health. It allocates more funds for building
      newer tertiary care hospitals and increases income tax exemptions for buying
      health insurance. The article explains that model that is being followed, as
      indicated by these measures, will create havoc to the lives of Indians and make
      them sicker and healthcare costlier. The budget is not in line with the actual
      priorities of India's health system and nor paves the road map for Universal
      Health Coverage. The Government of India needs to gets its priorities right. 

PMID- 25949962
TI  - Young Doctor Movements: motives for membership among aspiring and young family
      physicians.
AB  - BACKGROUND: Over the past decade, young doctor movements (YDMs) have gained
      recognition for their efforts in promoting the discipline of family medicine.
      With growth and expansion comes the need for an inquiry into the membership
      motives of current/intending members. AIM AND OBJECTIVES: This study was aimed at
      determining the main reasons why young and aspiring family physicians (FPs)
      joined their regional YDM. It was also concerned with determining the main
      factors that will make non-members want to join a YDM as well as assessing for
      differences in the responses within YDM members on the one hand, and between YDM
      members and non-members on the other. MATERIALS AND METHODS: This was a cross
      sectional web-based study. Using a list of 11 items generated following a series
      of discussions and feedback among selected FPs and FP trainees, respondents
      annotated levels of agreement on reasons for current or desired YDM membership.
      The Mann-Whitney U test was used to determine the distribution and differences in
      the mean of rank scores of the responses from YDM and non-YDM members while the
      Kruskal-Wallis test was used to describe same for the various YDMs. RESULTS: The
      total number of respondents was 200, out of which 102 (51.0%) were current YDM
      members, 97 (48.5%) were non-members and 1 (0.5%) respondent did not state
      his/her membership status. Non-YDM members indicated a predominantly
      academic/professional motive for membership while YDM members indicated the
      opportunity to socialise with FPs abroad and in their country as their foremost
      reasons for membership. A mixture of academic, professional and social motives
      was observed for respondents from Vasco da Gama; predominantly academic and
      professional motives for respondents from Spice route. CONCLUSIONS: While gaining
      recognition and improving one's practice may be the ultimate goal of an aspiring
      FP, socialising within a network of like-minded professionals maybe the young
      FP's way of coping with demands of the discipline.

PMID- 25949963
TI  - Is intermittent short-course anti-TB regimen as efficient and safe as daily anti
      TB regimen for treating childhood TB?
AB  - Childhood tuberculosis (TB) is a common clinical condition in low- and middle
      income nations like India where TB is endemic. Different guidelines vary in the
      recommendations on treatment regimes for childhood TB. Apart from clinical
      outcomes the decision to use one regimen over another also has an implication in
      the form of health system burden. The evidence summary presents the comparison
      between the intermittent regimens with the daily anti-TB regimen for childhood
      TB. 

PMID- 25949964
TI  - Menstruation related myths in India: strategies for combating it.
AB  - Menstruation is a phenomenon unique to girls. However, it has always been
      surrounded by taboos and myths that exclude women from many aspects of socio
      cultural life. In India, the topic has been a taboo until date. Such taboos about
      menstruation present in many societies impact on girls' and women's emotional
      state, mentality and lifestyle and most importantly, health. The challenge, of
      addressing the socio-cultural taboos and beliefs in menstruation, is further
      compounded by the low girls' knowledge levels and understandings of puberty,
      menstruation, and reproductive health. Thus, there is the need to follow a
      strategic approach in combating these issues. The current paper aims to discuss
      menstruation related myths prevalent in India, their impact on women's life,
      relevance of addressing these issues in primary care and a brief description
      about various strategies to combat them. 

PMID- 25949965
TI  - Childhood obesity: causes and consequences.
AB  - Childhood obesity has reached epidemic levels in developed as well as in
      developing countries. Overweight and obesity in childhood are known to have
      significant impact on both physical and psychological health. Overweight and
      obese children are likely to stay obese into adulthood and more likely to develop
      non-communicable diseases like diabetes and cardiovascular diseases at a younger
      age. The mechanism of obesity development is not fully understood and it is
      believed to be a disorder with multiple causes. Environmental factors, lifestyle
      preferences, and cultural environment play pivotal roles in the rising prevalence
      of obesity worldwide. In general, overweight and obesity are assumed to be the
      results of an increase in caloric and fat intake. On the other hand, there are
      supporting evidence that excessive sugar intake by soft drink, increased portion
      size, and steady decline in physical activity have been playing major roles in
      the rising rates of obesity all around the world. Childhood obesity can
      profoundly affect children's physical health, social, and emotional well-being,
      and self esteem. It is also associated with poor academic performance and a lower
      quality of life experienced by the child. Many co-morbid conditions like
      metabolic, cardiovascular, orthopedic, neurological, hepatic, pulmonary, and
      renal disorders are also seen in association with childhood obesity. 

PMID- 25949966
TI  - Resistant hypertension: an approach to management in primary care.
AB  - Hypertension is widely encountered in family medicine. Despite its prevalence,
      many patients have uncontrolled or difficult-to-control blood pressure. Resistant
      hypertension is defined as hypertension that is poorly responsive to treatment
      and requires the use of multiple medications to achieve acceptable blood pressure
      ranges. It may be a consequence of secondary hypertension or have no identifiable
      cause. Resistant hypertension is important to recognise because it places
      patients at risk of end-organ damage. Primary care physicians should be aware of
      the therapeutic approach for hypertension when traditional therapy fails. This
      article aims to familiarise readers with the evaluation and management of
      resistant hypertension by outlining the most recent evidence-based treatment
      options. 

PMID- 25949967
TI  - Addressing inequalities in oral health in India: need for skill mix in the dental
      workforce.
AB  - Dentistry has always been an under-resourced profession. There are three main
      issues that dentistry is facing in the modern era. Firstly, how to rectify the
      widely acknowledged geographical imbalance in the demand and supply of dental
      personnel, secondly, how to provide access to primary dental care to maximum
      number of people, and thirdly, how to achieve both of these aims within the
      financial restraints imposed by the central and state governments. The trends of
      oral diseases have changed significantly in the last 20 years. The two of the
      most common oral diseases that affect a majority of the population worldwide,
      namely dental caries and periodontitis, have been proved to be entirely
      preventable. Even for life-threatening oral diseases like oral cancer, the best
      possible available treatment is prevention. There is a growing consensus that
      appropriate skill mix can prove very beneficial in providing these preventive
      dental care services to the public and aid in achieving the goal of universal
      oral health coverage. Professions complementary to dentistry (PCD) have been
      found to be effective in reducing inequalities in oral health, improving access
      and spreading the messages of health promotion across entire spectrum of socio
      economic hierarchy in various studies conducted globally. This commentary
      provides a review of the effectiveness of skill mix in dentistry and a reflection
      on how this can be beneficial in achieving universal oral health care in India. 

PMID- 25949968
TI  - Intrauterine device survival in Iranian women: systematic review and meta
      analysis.
AB  - INTRODUCTION: The intrauterine device (IUD) is one of the modern contraception
      methods that is reversible, safe, effective, and with long-term efficacy. The
      problem of using this method is early discontinuation. The survival of the IUD
      use has been reported differently in different studies. In this meta-analysis, we
      estimated average time of surviving in Iranian women. MATERIALS AND METHODS: We
      evaluated the incident of IUD removed in the Iranian women with a broad
      systematic review of the literature regarding MOOSES criteria. ISI, Scopus,
      Medline, WHO, Cochrane, Web of Science, Biological abstracts, Google Scholar and
      DARE and Iran Medex, SID, Magiran and IranDoc were searched. We defined inclusion
      and exclusion criteria for selection of articles. All chosen articles were
      appraised using Critical Appraisal Skills Programme checklist. Data were
      extracted regarding prepared sheets. We used a Cochrane Q-test with a
      significance <0.1 for checking of heterogeneity of results. We defined I (2) = 50
      75% as a medium heterogeneity and I (2) >75% as high heterogeneity. We applied
      both fix and random effect model by comprehensive meta-analysis software.
      RESULTS: A total of 14 articles was included in the systematic review. These were
      obtained from screening 63 potentially relevant citations and reviewing 17 full
      text study articles. One-year survival of IUD, for the random effects model was
      78.4% (69.8-85.1%). Three-year survival for the random effects model was 69.4%
      (53.3-81.9%). Five years for the random effects model was 49.7% (36-63.4%).
      CONCLUSION: Above half of Iranian IUD users discontinued it within 5 years after
      insertion, it means half of IUD expected lifetime was used and make additional
      costs to the state and the consumer. To reduce these costs, it is recommended for
      Iranian women to use the IUD with 5-year survival, and they should be consulted
      before insertion.

PMID- 25949969
TI  - Effect of practice management softwares among physicians of developing countries
      with special reference to Indian scenario by Mixed Method Technique.
AB  - INTRODUCTION: Currently, many cheaper "practice management software" (PMS) are
      available in developing countries including India; despite their availability and
      benefits, its penetration and usage vary from low to moderate level, justifying
      the importance of this study area. MATERIALS AND METHODS: First preferred
      reporting items for systematic-review and meta-analysis (2009) guidelines were
      considered; followed by an extensive systematic-review of available studies in
      literature related to developing countries, on key search term from main
      abstracting databases: PubMed, EMBASE, EBSCO, BIO-MED Central, Cochrane Library,
      world CAT-library till 15 June 2014; where any kind of article whether published
      or unpublished, in any sort or form or any language indicating the software usage
      were included. Thereafter, meta-analysis on Indian studies revealing the
      magnitude of usage in Indian scenario by Open Meta-(analyst) software using
      binary random effects (REs) model was done. Studies from developed countries were
      excluded in our study. RESULTS: Of 57 studies included in a systematic review
      from developing countries, only 4 Indian studies were found eligible for meta
      analysis. RE model revealed although not-significant results (total participants
      = 243,526; range: 100-226,228, overall odds ratio = 2.85, 95% confidence interval
      = P < 0.05 and tests for heterogeneity: Q [df = 3] = 0.8 Het. P = 0.85). The
      overall magnitude of usage of PMS on Indian physicians practice was however found
      between 10% and 45%. CONCLUSION: Although variable and nonsignificant effect of
      usage of PM software on practice of physicians in developing countries like India
      was found; there is a need to recognize the hidden potential of this system.
      Hence, more in-depth research in future needs to be done, in order to find a real
      impact of this system.

PMID- 25949970
TI  - A retrospective non-comparative analysis of the quality of care for
      osteoarthritis at the general out-patient department of Jos University Teaching
      Hospital, Nigeria.
AB  - BACKGROUND: Osteoarthritis is a common condition in primary care and is often
      associated with disability and limitation of function requiring holistic care.
      AIM: The aim of this audit was to assess the quality of care provided by family
      physicians in the management of osteoarthritis at the General Out-patient
      Department (GOPD) of Jos University Teaching Hospital (JUTH) as well as ascertain
      if such care was in line with evidence-based medicine. METHODS: This was a
      retrospective noncomparative study. The recommendations of the Nigerian Standard
      Treatment Guidelines 2008 and the National Institute for Health and Care
      Excellence 2014 guidelines were used to form standard targets for each of the
      structural, process and outcome components of the care process. Each of the
      consultation rooms was inspected for the structure components of the care
      process. For the process and outcome components of care, the medical records of
      all patients being managed for osteoarthritis at the GOPD of JUTH over a 1-year
      period were retrieved and studied. RESULTS: For one aspect of the structural
      component (i.e. availability of weighing scale for each consultation room), 80%
      of the standard target was met which was below the standard target of 100%. The
      highest performance under the process component was for the documentation of risk
      associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and
      documentation for NSAID/cyclooxygenase-2 inhibitors use with a gastro-protective
      agent. For both of these, 22.4% of the standard target was met; less than the
      standard target of 100% and 80% respectively. None of the standard targets for
      the outcome component were met. CONCLUSION: The quality of care for patients with
      osteoarthritis in this practice setting was sub-optimal. More can be done by
      family physicians with regards provision of comprehensive care for patients
      suffering from osteoarthritis.

PMID- 25949971
TI  - How healthy is our geriatric population? a community-based cross-sectional study.
AB  - INTRODUCTION: With the rise in aged population there is a greater need to look
      into their nutritional and physical disability aspects which is otherwise
      neglected. The study aimed to assess the prevalence of malnutrition, anemia and
      physical disability among the community-dwelling aged population. MATERIALS AND
      METHODS: A cross-sectional study was carried out in a rural block of north Tamil
      Nadu. Seventeen villages were selected using cluster sampling based on
      probability proportional to size. A total of 340 participants of age 60 years and
      above were selected from these clusters using simple random sampling. Nutritional
      status and physical disability were assessed using mini nutritional assessment
      scale and Barthel index. Blood samples were collected for anemia. Appropriate
      data entry and statistical analysis were done in EPIDATA and SPSS 16. STATISTICAL
      ANALYSIS USED: Besides calculating prevalence chi square and logistic regression
      tests were done to identify associated risk factors. RESULTS AND CONCLUSIONS: The
      overall prevalence of "at risk of malnutrition," anemia and physical disability
      were 10.9%, 38.2% and 20.6%, respectively. None of the community-dwelling aged
      population was found to be malnourished. Anemia and physical disability were
      significantly higher among the older age group [(OR 2.29 (1.17-4.89), (OR 2.81
      (95% CI 1.31-6.04), respectively]. Similarly women were more affected with
      physical disability than men (OR 2.27 (1.28-4.02)). Further studies need to be
      done to explore the reasons for high prevalence of anemia.

PMID- 25949972
TI  - Mothers' understanding of childhood malaria and practices in rural communities of
      Ise-Orun, Nigeria: implications for malaria control.
AB  - INTRODUCTION: Regular evaluations of communities' understanding of malaria
      related practices are essential for control of the disease in endemic areas. This
      study was aimed at investigating the perceptions, prevention and treatments
      practices for childhood malaria by mothers in rural communities. MATERIALS AND
      METHODS: We conducted a community-based cross-sectional study at rural
      communities of Ise-Orun local Government area, Nigeria. We randomly sampled 422
      mothers of children less than 5 years and administered a validated questionnaire
      to assess their perceptions and practices relating to childhood malaria. We used
      a 10-point scale to assess perception and classified it as good (>=5) or poor
      (<5). Predictive factors for poor perceptions were identified using logistic
      regression. RESULTS: Approximately 51% of the mothers had poor perception and
      14.2% ascribed malaria illness to mosquito bite only. Majority (85.8%) of the
      mothers practiced malaria preventive measures, including: Insecticide treated
      nets (70.0%), chemoprophylaxis (20.1%) and environmental sanitation (44.8%). Of
      the 200 mothers whose children had malaria fever within the 3 months prior to the
      study visits, home treatment was adopted by 87.5%. Local herbal remedies were
      combined with orthodox medicine in the treatments of malaria for 91.5% of the
      children. The main reasons for not seeking medical treatment at existing formal
      health facilities were "high cost", "challenges of access to facilities" and
      "mothers' preference for herbal remedies". Lack of formal education was the only
      independent predictor of poor malaria perceptions among mothers (OR = 1.91, 95%
      CI = 1.18, 3.12). CONCLUSIONS: Considerable misconceptions about malaria exist
      among mothers in the rural communities. The implications for malaria control in
      holoendemic areas are highlighted.

PMID- 25949973
TI  - Sleep-patterns, sleep hygiene behaviors and parental monitoring among Bahrain
      based Indian adolescents.
AB  - INTRODUCTION: Sleep plays an important role in adolescent's health and undergoes
      substantial changes with puberty and physical maturation with a preference for
      later bed times. Evidence shows that many adolescents are not obtaining the
      required amounts of sleep which is 9.25 h, due to inadequate sleep practices,
      academic and societal demands. This study aims at describing the (1) sleep
      patterns of adolescents on school days and weekends, (2) sleep hygiene practices
      and the extent of parental monitoring and (3) gender and grade level differences
      in sleep duration and sleep hygiene practices among Indian adolescents in
      Bahrain. MATERIALS AND METHODS: Study used a descriptive correlational design. A
      total of 145 adolescents from 11 to 17 years from grade 6 to 12 were selected
      using convenience sampling. Data was collected from November 2012 to March 2013.
      A structured questionnaire for sleep patterns and Mastin et al.'s Sleep Hygiene
      Index for assessing sleep hygiene practices were used. RESULTS: The adolescents'
      total sleep duration was 7.07 +/- 1.13 hours. A highly significant difference in
      sleep duration on school days and weekends between adolescents of various grade
      levels (P < 0.001 and 0.001, respectively) and between parental monitoring at the
      time of getting up on school days and sleep duration (P value 0.026 at 0.05 level
      of significance) was found. Gender was not significant with the sleep duration,
      and also with Sleep Hygiene Index scores. CONCLUSION: The results suggest that
      there is a high prevalence of insufficient sleep and irregular bed-time schedule
      among Indian adolescents in Bahrain. Interventions directed toward improving
      sleep and promoting good sleep hygiene strategies are required to improve the
      physical and emotional health of adolescents.

PMID- 25949974
TI  - Drug-induced hepatitis and the risk factors for liver injury in pulmonary
      tuberculosis patients.
AB  - INTRODUCTION: Short-course chemotherapy containing rifampicin and isoniazid in
      combination has proved to be highly effective in the treatment of tuberculosis,
      but one of its adverse effects is hepatotoxicity. Various risk factors have been
      found to be associated with drug-induced liver injury (DILI) in general
      population. The study aimed to determine the prevalence of drug-induced hepatitis
      and the risk factors associated with the DILI among the patients of pulmonary
      tuberculosis in Indian patients. SETTING AND DESIGN: Prospective nested case
      control study. MATERIALS AND METHODS: Out of the cohort of 3900 tuberculosis
      patients who were initiated on anti-tubercular therapy, 150 patients who
      developed drug-induced liver injury due to short-course chemotherapy under RNTCP
      were included in the analysis. Thirty cases were being followed up in our
      hospital and other 120 were referred to us for the management of drug-induced
      hepatitis from the primary health centers. The diagnostic criteria's for DILI
      were made according to the American Thoracic Society criteria. Analyses of
      various risk factors were done for the development of DILI. RESULTS: The
      prevalence of DILI in the present study was 3.8%. It was observed that DILI
      patients were older and their serum albumin levels were lower, and they had
      multiple co-morbid conditions. Regular alcohol intake, more extensive disease
      associated with radiological and female gender were observed to be independent
      risk factors for the development of DILI. CONCLUSIONS: Of the various risk
      factors analyzed, advanced age, hypoalbuminemia, regular alcohol intake and
      advanced nature of the disease were independent risk factors for the development
      of DILI. The risk of development of hepatitis is increased in the presence of one
      or more of these risk factors.

PMID- 25949975
TI  - Awareness, perception and practice of stakeholders in India regarding Village
      Health and Nutrition Day.
AB  - BACKGROUND: Village Health and Nutrition Day (VHND) is a community-based health
      service package delivered on a fixed day approach. Services like early
      registration of pregnancy, regular antenatal care and postnatal care, growth
      monitoring and referral of sick children, discussion of health topics to generate
      awareness, and convergence between health and ICDS, are delivered every month at
      VHND at the Anganwadi Center. This study explores the awareness, perception and
      practice of service providers, and beneficiaries, regarding VHND. MATERIALS AND
      METHODS: It was a cross-sectional study conducted in Odisha during December 2009
      November 2010. Personal interviews were conducted at the VHND sessions with 111
      beneficiaries and 45 service providers using a semi-structured schedule to know
      their awareness, perception and practice regarding VHND sessions. Data analysis
      was done and reported as simple percentages. RESULTS: Most of the health worker
      females and anganwadi workers considered health awareness as a key component of
      VHND. 52% of HWFs and 41% of AWWs had misconception about additional roles and
      responsibilities. 34% of beneficiaries had knowledge regarding fixed day approach
      of VHND, while 24% did not have knowledge regarding any of its purpose. Only 8%
      of referral cases had complete knowledge on the reason of referral. There was
      significant difference in between awareness and practice among the blocks.
      CONCLUSION: Service providers' orientation should be improved. Behavior change
      communication activities should also be increased by the state. Referral cases
      should be properly counseled. The community believed that such a program should
      continue with better package and quality of services.

PMID- 25949976
TI  - Availability of Village Health and Nutrition Day services in Uttarakhand, India.
AB  - BACKGROUND: Village Health and Nutrition Day (VHND) was identified to provide
      primary care services (health, nutrition and sanitation) at village level under
      National Rural Health Mission. AIM: The study aimed to assess availability of
      health, nutrition and sanitation services, required instruments/equipment and
      medicines at VHND with client satisfaction from the VHND services. MATERIALS AND
      METHODS: A cross-sectional study was conducted in three districts of Uttarakhand
      at Nainital, Tehri-Garhwal and Chamoli involving 24 villages in six blocks using
      multistage stratified sampling using predesigned pretested observation checklists
      (quantitative data). All the concerned functionaries of health, Integrated Child
      Development Services and Panchayati Raj Institution were interviewed (qualitative
      data) to understand the gap in services and remediation. RESULTS: Of the 24 VHNDs
      observed, blood pressure measurement was done at 11 (45.83%) and weight at 13
      (54.17%) sites in ante-natal care services; non-availability of blood pressure
      instrument and adult weighing machine were 45.83% and 41.66% sites, respectively.
      Immunization for children was provided at 22 sites; however, availability of
      other services were poor-vitamin A (three), growth monitoring of children
      (seven); supplementary nutrition (five); identification of households for
      construction of toilet (eight). Yet, one-third of clients provided three and four
      for satisfaction from VHND services on the scale score of 1-5. CONCLUSION: It was
      noted that none of the VHND site was providing all the stipulated services,
      though immunization was provided mostly. Anganwadi centers were lacking
      availability of various essential instruments and equipment. So regular
      orientation of village functionaries for ensuring all the VHND services with the
      availability of required logistic is recommended.

PMID- 25949977
TI  - Maternal and fetal outcome in pre-eclampsia in a secondary care hospital in South
      India.
AB  - BACKGROUND: Hypertensive disorders in pregnancy are one of the common causes for
      perinatal and maternal morbidity and mortality in developing countries. Pre
      eclampsia is a condition which typically occurs after 20 weeks of gestation and
      has high blood pressure as the main contributing factor. The aim was to study the
      effects of pre-eclampsia on the mother and the fetus in rural South Indian
      population. MATERIALS AND METHODS: This was a descriptive study conducted in a
      secondary level hospital in rural South India. A total of 1900 antenatal women
      were screened for pre-eclampsia during the period August 2010 to July 2011 to
      study the effects on the mother and fetus. RESULTS: Of the 1900 women screened 93
      were detected with pre-eclampsia in the study. Among these, 46.23% were
      primigravida, 30.1% belonged to socio-economic class 4 and 48.8% were among those
      with BMI 26-30. The incidence of severe pre-eclampsia was higher in the
      unregistered women. The most common maternal complication was antepartum
      hemorrhage (13.9%) and the most common neonatal complication was prematurity
      (23.65%). CONCLUSIONS: Treating anemia and improving socioeconomic status will
      improve maternal and neonatal outcome in pre-eclampsia. Antenatal care and
      educating women on significance of symptoms will markedly improve perinatal
      morbidity and mortality. Prematurity, growth restriction and low birth weight are
      neonatal complications to be anticipated and dealt with when the mother has pre
      eclampsia. A good neonatal intensive care unit will help improve neonatal
      outcomes.

PMID- 25949978
TI  - Tobacco use, attitudes and cessation practices among healthcare workers of a city
      health department in Southern India.
AB  - OBJECTIVE: To assess tobacco use, attitudes and cessation practices among
      healthcare workers of a municipal health department in southern India. MATERIALS
      AND METHODS: We undertook a cross-sectional epidemiologic study to investigate
      558 healthcare workers from three groups (doctors, auxiliary nurses and community
      link workers (LWs)) employed by the Bangalore city corporation in southern India.
      Outcomes included self-reported tobacco use status and attitudes (for all
      workers), and (for doctors) self-report of performance of "5-A" tobacco cessation
      interventions: Asking, advising, assessing, assisting, or arranging follow-up for
      tobacco control, in their client population. RESULTS: Doctors reported higher
      tobacco use rates (6.9%) compared to LW (2%) and nurses (<1%) but were less
      interested in further tobacco control training (77%) compared to the others
      (>95%). Many doctors reported asking (100%) and advising (78%) about tobacco use
      but much fewer were assessing intention/motivation to quit (24%), assisting with
      quitting (19%), and arranging follow-up for quitting and relapse prevention (9%).
      CONCLUSION: Tailored training in tobacco control would enable doctors, nurses and
      outreach workers involved in primary healthcare delivery to be better equipped to
      deal with a major cause of morbidity and mortality among urban communities in the
      21(st) century.

PMID- 25949979
TI  - Reliability of dipstick assay in predicting urinary tract infection.
AB  - AIMS: Urine dipstick analysis is a quick, cheap and a useful test in predicting
      Urinary Tract Infection (UTI) in hospitalized patients. Our aim is to evaluate
      the reliability (sensitivity) of urine dipstick analysis against urine culture in
      the diagnosis of UTI. MATERIALS AND METHODS: Patients admitted to our hospital
      suspected of having UTI, with positive urine cultures were included in this study
      from a 2-year period (January 2011 to December 2012). Dipstick urinalysis was
      done using multistix 10 SG (Siemens) and clinitek advantus analyzer. The
      sensitivity of dipstick nitrites, leukocyte esterase and blood in these culture
      positive UTI patients was calculated retrospectively. RESULTS: Urine dipstick
      analysis of 635 urine culture-positive patients was studied. The sensitivity of
      nitrite alone and leukocyte esterase alone were 23.31% and 48.5%, respectively.
      The sensitivity of blood alone in positive urine culture was 63.94%, which was
      the highest sensitivity for a single screening test. The presence of leukocyte
      esterase and/or blood increased the sensitivity to 72.28%. The sensitivity was
      found to be the highest when nitrite, leukocyte and blood were considered
      together. CONCLUSIONS: Nitrite test and leukocyte esterase test when used
      individually is not reliable to rule out UTI. Hence, symptomatic UTI patients
      with negative dipstick assay should be subjected to urine culture for a proper
      management.

PMID- 25949980
TI  - Ciprofloxacin induced bullous fixed drug reaction: three case reports.
AB  - Cutaneous adverse drug reactions (ADRs) are seen in about 1-2% cases. Fixed drug
      reaction (FDR) is responsible for about 10% of all ADRs. It is a delayed type of
      hypersensitivity reaction that occurs as lesions recurs at the same skin site due
      to repeated intake of an offending drug. The most common drugs causing fixed drug
      eruption (FDE) are analgesics, antibiotics, muscle relaxants and anticonvulsants.
      FDE due to ciprofloxacin has been reported earlier also, but bullous variant of
      FDR is rare. We hereby report three case reports of bullous FDR caused due to
      ciprofloxacin. 

PMID- 25949981
TI  - Myriad presentations of penile fracture: report of three cases and review of
      literature.
AB  - Penile fracture is an unusual though not a rare condition but underreported. It
      is defined classically as the disruption of the tunica albuginea with rupture of
      the corpus cavernosum. Penile fracture can be misdiagnosed with rupture of corpus
      spongiosum clinically. Therefore, we are presenting three cases due to its varied
      clinical presentation and management. In first patient, there was a tear in the
      corpus spongiosum and a partial tear in the ventral urethra. Both defects were
      repaired with interrupted sutures. In the second patient, there was a rupture of
      corpus cavernosum, which was primarily repaired. After 1-year of primary surgery,
      patient again came with similar complaints, and diagnosis of scar dehiscence was
      made. Patient was treated conservatively with satisfactory results on follow-up.
      Third patient came with a history of 1-week. Intra-operative findings revealed
      only hematoma without any defect in corpora cavernosum, corpus spongiosum, and
      urethra. Only evacuation of hematoma was done. Early surgical treatment of penile
      fracture is advantageous. In recurrent penile fracture, if no penile deformity or
      any reasonable clinical and radiological evidence, then conservative management
      is advocated. Even when presentation is delayed up to 1-week, operative
      management has shown good results. 

PMID- 25949982
TI  - Immunosuppressive treatment for immune thrombocytopenia which masked Graves'
      disease.
AB  - A 71-year-old female patient followed primary immune thrombocytopenia (ITP) was
      admitted to endocrinology unit with excessive sweating. We started methimazole
      for Graves' disease. Without any additional immunosuppressive treatment, at week
      12 of methimazole therapy, thyroid stimulating hormone (TSH) levels returned to
      normal, and platelet counts rose to tolerable levels. When her hospital records
      were analyzed, they revealed that a year ago, when she had been diagnosed with
      ITP, her TSH values had been suppressed. After immunosuppressive therapy, her
      platelet values were maintained at normal levels, and during her control visits,
      her TSH levels were measured twice and were within normal limits. We think that
      immunosuppressive therapy for ITP without considering thyroid function tests may
      result in a transient euthyroid state, which potentially masks Graves' disease
      accompanying immunosuppressive therapy and associated recurrent ITP attacks. 

PMID- 25949983
TI  - Hypokalemic quadriparesis in dengue.
AB  - Dengue infection is the leading cause of illness and death in tropical and
      subtropical regions of the world. The common complications associated with dengue
      fever are usual hematological abnormalities, shock, and organ failure. The
      neurological complications of dengue are uncommon. However, evidence of dengue
      virus neurotropism and complications has been slowly but surely rising as seen
      from increased literature on this subject over the last decade. We report an
      uncommon case of hypokalemic quadriparesis with dengue that had a favorable
      outcome. 

PMID- 25949984
TI  - T-cell lymphoma masquerading as extrapulmonary tuberculosis: case report and
      review of literature.
AB  - It is often difficult to establish confirmatory diagnosis in cases of
      extrapulmonary tuberculosis (TB) because of its paucibacillary nature and
      difficulty in accessing the involved organs. In several cases, empirical anti
      tubercular treatment is started, and the patient is followed-up closely for
      response. In countries with high prevalence of TB, it is a reasonably good
      strategy and works most of the times. However, catastrophe may occur when
      aggressive lymphomas masquerade as TB. 

PMID- 25949985
TI  - Kyrle's disease in a patient of diabetes mellitus and chronic renal failure on
      dialysis.
AB  - Kyrle's disease (KD) is an acquired perforating dermatosis associated with an
      underlying disorder such as diabetes mellitus or chronic renal failure. It
      presents as multiple discrete, eruptive papules with a central crust or plug,
      often on the lower extremities. A keratotic plug is seen histologically in an
      atrophic epidermis and may penetrate the papillary dermis with transepidermal
      elimination of keratotic debris without collagen or elastic fibers. Various
      therapies have been reported that include cryotherapy, laser therapy, narrow-band
      ultraviolet B and use of topical or systemic retinoids. Hereby a case of 64-year
      old male, a known case of diabetes mellitus, hypertension and chronic renal
      failure who developed KD is presented. 

PMID- 25949986
TI  - Tobacco based dentifrices: still not squeezed out.

PMID- 25949987
TI  - A comment on the drug utilization pattern in chronic obstructive pulmonary
      disease.

PMID- 25949988
TI  - Author reply: comment on the drug utilization pattern in chronic obstructive
      pulmonary disease.

PMID- 25949989
TI  - Pulmonary edema - cardiogenic or noncardiogenic?

PMID- 25949991
TI  - Improvement of starch digestion using alpha-amylase entrapped in pectin-polyvinyl
      alcohol blend.
AB  - Polyvinyl alcohol (PVA) and pectin blends were used to entrap alpha-amylase
      (Termamyl) using glutaraldehyde as a cross-linker. The effect of glutaraldehyde
      concentration (0.25, 0.5, 0.75, 1.0, and 1.25%) on the activity of the
      immobilized enzyme and rate of enzyme released was tested during a 24 h period.
      Characteristics of the material, such as scanning electron microscopy (SEM),
      tensile strength (TS), elongation, and rate of dissolution in water (pH 5.7),
      ruminal buffering solution (pH 7.0), and reactor containing 0.1 mol L(-1) sodium
      phosphate buffer (pH 6.5), were also analyzed. SEM results showed that the
      surfaces of the pectin/PVA/amylase films were highly irregular and rough. TS
      values increased as a function of glutaraldehyde concentration, whereas
      percentage of elongation (%E) decreased. Pectin/PVA/amylase films presented
      similar values of solubility in the tested solvents. The material obtained with
      0.25% glutaraldehyde performed best with repeated use (active for 24 h), in a
      phosphate buffer reactor. By contrast, the material obtained with 1.25%
      glutaraldehyde presented higher performance during in vitro testing using an
      artificial rumen. The results suggest that pectin/PVA/amylase is a highly
      promising material for biotechnological applications. 

PMID- 25949992
TI  - Helicobacter pylori and pathogenesis.

PMID- 25949993
TI  - Cross-linking and corneal imaging advances.

PMID- 25949995
TI  - Prehospital volume therapy as an independent risk factor after trauma.
AB  - BACKGROUND: Prehospital volume therapy remains widely used after trauma, while
      evidence regarding its disadvantages is growing. The primary objective of this
      study was to investigate the volume administered in a prehospital setting as an
      independent risk factor for mortality. MATERIAL AND METHODS: Patients who met the
      following criteria were analyzed retrospectively: Injury Severity Score=16,
      primary admission (between 2002 and 2010), and age=16 years. The following data
      had to be available: volume administered (including packed red cells), blood
      pressure, Glasgow Coma Scale, therapeutic measures, and laboratory results.
      Following a univariate analysis, independent risk factors for mortality after
      trauma were investigated using a multivariate regression analysis. RESULTS: A
      collective of 7,641 patients met the inclusion criteria, showing that increasing
      volumes administered in a prehospital setting were an independent risk factor for
      mortality (odds ratio: 1.34). This tendency was even more pronounced in patients
      without severe traumatic brain injury (TBI) (odds ratio: 2.71), while the
      opposite tendency was observed in patients with TBI. CONCLUSIONS: Prehospital
      volume therapy in patients without severe TBI represents an independent risk
      factor for mortality. In such cases, respiratory and circulatory conditions
      should be stabilized during permissive hypotension, and patient transfer should
      not be delayed.

PMID- 25949994
TI  - Heart failure: advanced development in genetics and epigenetics.
AB  - Heart failure (HF) is a complex pathophysiological syndrome that arises from a
      primary defect in the ability of the heart to take in and/or eject sufficient
      blood. Genetic mutations associated with familial dilated cardiomyopathy,
      hypertrophic cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy
      can contribute to the various pathologies of HF. Therefore, genetic screening
      could be an approach for guiding individualized therapies and surveillance. In
      addition, epigenetic regulation occurs via key mechanisms, including ATP
      dependent chromatin remodeling, DNA methylation, histone modification, and RNA
      based mechanisms. MicroRNA is also a hot spot in HF research. This review gives
      an overview of genetic mutations associated with cardiomyopathy and the roles of
      some epigenetic mechanisms in HF. 

PMID- 25949996
TI  - Antitumor phenylpropanoids found in essential oils.
AB  - The search for new bioactive substances with anticancer activity and the
      understanding of their mechanisms of action are high-priorities in the research
      effort toward more effective treatments for cancer. The phenylpropanoids are
      natural products found in many aromatic and medicinal plants, food, and essential
      oils. They exhibit various pharmacological activities and have applications in
      the pharmaceutical industry. In this review, the anticancer potential of 17
      phenylpropanoids and derivatives from essential oils is discussed. Chemical
      structures, experimental report, and mechanisms of action of bioactive substances
      are presented. 

PMID- 25949998
TI  - A method for generating new datasets based on copy number for cancer analysis.
AB  - New data sources for the analysis of cancer data are rapidly supplementing the
      large number of gene-expression markers used for current methods of analysis.
      Significant among these new sources are copy number variation (CNV) datasets,
      which typically enumerate several hundred thousand CNVs distributed throughout
      the genome. Several useful algorithms allow systems-level analyses of such
      datasets. However, these rich data sources have not yet been analyzed as deeply
      as gene-expression data. To address this issue, the extensive toolsets used for
      analyzing expression data in cancerous and noncancerous tissue (e.g., gene set
      enrichment analysis and phenotype prediction) could be redirected to extract a
      great deal of predictive information from CNV data, in particular those derived
      from cancers. Here we present a software package capable of preprocessing
      standard Agilent copy number datasets into a form to which essentially all
      expression analysis tools can be applied. We illustrate the use of this toolset
      in predicting the survival time of patients with ovarian cancer or glioblastoma
      multiforme and also provide an analysis of gene- and pathway-level deletions in
      these two types of cancer. 

PMID- 25949997
TI  - Transgenic carrot expressing fusion protein comprising M. tuberculosis antigens
      induces immune response in mice.
AB  - Tuberculosis remains one of the major infectious diseases, which continues to
      pose a major global health problem. Transgenic plants may serve as bioreactors to
      produce heterologous proteins including antibodies, antigens, and hormones. In
      the present study, a genetic construct has been designed that comprises the
      Mycobacterium tuberculosis genes cfp10, esat6 and dIFN gene, which encode
      deltaferon, a recombinant analog of the human gamma-interferon designed for
      expression in plant tissues. This construct was transferred to the carrot (Daucus
      carota L.) genome by Agrobacterium-mediated transformation. This study
      demonstrates that the fusion protein CFP10-ESAT6-dIFN is synthesized in the
      transgenic carrot storage roots. The protein is able to induce both humoral and
      cell-mediated immune responses in laboratory animals (mice) when administered
      either orally or by injection. It should be emphasized that M. tuberculosis
      antigens contained in the fusion protein have no cytotoxic effect on peripheral
      blood mononuclear cells. 

PMID- 25949999
TI  - First report of hepatitis E virus infection in sika deer in China.
AB  - Hepatitis E virus (HEV), a single stranded RNA, nonenveloped virus, belongs to
      the genus Hepevirus, in the family of Hepeviridae. In this study, 46 (5.43%) out
      of the 847 serum samples from sika deer (Cervus nippon) were detected as
      seropositive with hepatitis E virus (HEV) by enzyme linked immunosorbent assay
      (ELISA). These samples were collected from Inner Mongolia and Jilin and
      Heilongjiang provinces in China, between October 2012 and October 2013.
      Seroprevalence of HEV infection in male and female deer was 4.82% and 6.52%,
      respectively. HEV seroprevalence in sika deer from different geographical
      locations varied from 3.13% to 6.73%. There was no significant difference in HEV
      seroprevalence between sika deer collected in autumn (5.65%) and winter (4.85%).
      This is the first report of HEV seroprevalence in sika deer in China, which will
      provide foundation information for estimating the effectiveness of future
      measures to control HEV infection in sika deer in China and assessing the
      potential risk of humans infected with HEV after consumption of undercooked or
      raw meat from infected sika deer. 

PMID- 25950000
TI  - TTBK2: a tau protein kinase beyond tau phosphorylation.
AB  - Tau tubulin kinase 2 (TTBK2) is a kinase known to phosphorylate tau and tubulin.
      It has recently drawn much attention due to its involvement in multiple important
      cellular processes. Here, we review the current understanding of TTBK2, including
      its sequence, structure, binding sites, phosphorylation substrates, and cellular
      processes involved. TTBK2 possesses a casein kinase 1 (CK1) kinase domain
      followed by a ~900 amino acid segment, potentially responsible for its
      localization and substrate recruitment. It is known to bind to CEP164, a
      centriolar protein, and EB1, a microtubule plus-end tracking protein. In addition
      to autophosphorylation, known phosphorylation substrates of TTBK2 include tau,
      tubulin, CEP164, CEP97, and TDP-43, a neurodegeneration-associated protein.
      Mutations of TTBK2 are associated with spinocerebellar ataxia type 11. In
      addition, TTBK2 is essential for regulating the growth of axonemal microtubules
      in ciliogenesis. It also plays roles in resistance of cancer target therapies and
      in regulating glucose and GABA transport. Reported sites of TTBK2 localization
      include the centriole/basal body, the midbody, and possibly the mitotic spindles.
      Together, TTBK2 is a multifunctional kinase involved in important cellular
      processes and demands augmented efforts in investigating its functions. 

PMID- 25950001
TI  - Alpha-mangostin attenuation of hyperglycemia-induced ocular hypoperfusion and
      blood retinal barrier leakage in the early stage of type 2 diabetes rats.
AB  - The present study examined effects of alpha-mangostin (alpha-MG) supplementation
      on the retinal microvasculature, including ocular blood flow (OBF) and blood
      retinal barrier (BRB) permeability in a type 2 diabetic animal model. Male
      Sprague-Dawley rats were divided into four groups: normal control and diabetes
      with or without alpha-MG supplementation. Alpha-mangostin (200 mg/Kg/day) was
      administered by gavage feeding for 8 weeks. The effects of alpha-MG on
      biochemical and physiological parameters including mean arterial pressure (MAP),
      OBF, and BRB leakage were investigated. Additionally, levels of retinal
      malondialdehyde (MDA), advance glycation end products (AGEs), receptor of advance
      glycation end products (RAGE), tumour necrosis factor alpha (TNF-alpha), and
      vascular endothelial growth factor (VEGF) were evaluated. The elevated blood
      glucose, HbA1c, cholesterol, triglyceride, serum insulin, and HOMA-IR were
      observed in DM2 rats. Moreover, DM2 rats had significantly decreased OBF but
      statistically increased MAP and leakage of the BRB. The alpha-MG-treated DM2 rats
      showed significantly lower levels of retinal MDA, AGEs, RAGE, TNF-alpha, and VEGF
      than the untreated group. Interestingly, alpha-MG supplementation significantly
      increased OBF while it decreased MAP and leakage of BRB. In conclusion, alpha-MG
      supplementation could restore OBF and improve the BRB integrity, indicating its
      properties closely associated with antihyperglycemic, antioxidant, anti
      inflammatory, and antiglycation activities. 

PMID- 25950002
TI  - Hepatoprotective and antiviral efficacy of Acacia mellifera leaves fractions
      against hepatitis B virus.
AB  - The present study investigated the hepatoprotective and anti-HBV efficacy of
      Acacia mellifera (AM) leaves extracts. The crude ethanolic-extract, including
      organic and aqueous fractions, were tested for cytotoxicity on HepG2 and
      HepG2.2.15 cells (IC50=684 MUg/mL). Of these, the ethyl acetate and aqueous
      fractions showed the most promising, dose-dependent hepatoprotection in DCFH
      toxicated cells at 48 h. In CCl4-injured rats, oral administration of AM ethanol
      extract (250 and 500 mg/kg.bw) for three weeks significantly normalized the sera
      aminotransferases, alkaline phosphatase, bilirubin, cholesterol, triglycerides,
      and lipoprotein levels and elevated tissue nonprotein sulphydryl and total
      protein. The histopathology of dissected livers also revealed that AM cured the
      tissue lesions. The phytochemical screening of the fractions showed presence of
      alkaloids, flavonoids, tannins, sterols, and saponins. Further, anti-HBV
      potential of the fractions was evaluated on HepG2.2.15 cells. Of these, the n
      butanol and aqueous fractions exhibited the best inhibitory effects on HBsAg and
      HBeAg expressions in dose- and time-dependent manner. Taken together, while the
      ethyl acetate and aqueous fractions exhibited the most promising
      antioxidant/hepatoprotective and anti-HBV activity, respectively, the n-butanol
      partition showed both activities. Therefore, the therapeutic potential of AM
      extracts warrants further isolation of the active principle(s) and its
      phytochemical as well as biological studies.

PMID- 25950003
TI  - Minocycline protection of neomycin induced hearing loss in gerbils.
AB  - This animal study was designed to determine if minocycline ameliorates cochlear
      damage is caused by intratympanic injection of the ototoxic aminoglycoside
      antibiotic neomycin. Baseline auditory-evoked brainstem responses were measured
      in gerbils that received 40 mM intratympanic neomycin either with 0, 1.2, or 1.5
      mg/kg intraperitoneal minocycline. Four weeks later auditory-evoked brainstem
      responses were measured and compared to the baseline measurements. Minocycline
      treatments of 1.2 mg/kg and 1.5 mg/kg resulted in significantly lower threshold
      increases compared to 0 mg/kg, indicating protection of hearing loss between 6
      kHz and 19 kHz. Cochleae were processed for histology and sectioned to allow
      quantification of the spiral ganglion neurons and histological evaluation of
      organ of Corti. Significant reduction of spiral ganglion neuron density was
      demonstrated in animals that did not receive minocycline, indicating that those
      receiving minocycline demonstrated enhanced survival of spiral ganglion neurons,
      enhanced survival of sensory hairs cells and spiral ganglion neurons, and reduced
      hearing threshold elevation correlates with minocycline treatment demonstrating
      that neomycin induced hearing loss can be reduced by the simultaneous application
      of minocycline. 

PMID- 25950004
TI  - Osteogenic biomaterials in contemporary dentistry.

PMID- 25950005
TI  - Effect of various concentrations of caffeine, pentoxifylline, and kallikrein on
      hyperactivation of frozen bovine semen.
AB  - Caffeine, pentoxifylline, and kallikrein are substances that affect the
      efficiency of sperms in the fertilization process; however, they have not been
      adequately studied. The present study aimed to examine the influence of caffeine,
      kallikrein, and pentoxifylline on sperm motility in bovine as well as investigate
      their optimum concentrations for increasing the movement of sperms in bovine.
      Frozen bovine sperms were thawed in universal IVF medium supplemented with 1, 5,
      and 10 mM caffeine or pentoxifylline or 1, 4, and 8 U/mL kallikrein and were then
      incubated for 30 min. Treated semen parameters were analyzed using a computer
      assisted semen analyzer (CASA). Data analysis showed that the mean values
      concerning progression and motility of sperm increased in caffeine and
      pentoxifylline treatments when compared with the kallikrein group. The obtained
      results revealed that kallikrein is not necessary for the improvement of bovine
      sperm motility. Additionally, our results revealed that 5 mM from caffeine was
      the best concentration added to the medium, followed by 1 or 5 mM from
      pentoxifylline. Therefore, it is concluded from the present study that caffeine
      has hyperactivation efficacy at 5 mM concentration compared to other treatments. 

PMID- 25950006
TI  - Aberrant phenotype in human endothelial cells of diabetic origin: implications
      for saphenous vein graft failure?
AB  - Type 2 diabetes (T2DM) confers increased risk of endothelial dysfunction,
      coronary heart disease, and vulnerability to vein graft failure after bypass
      grafting, despite glycaemic control. This study explored the concept that
      endothelial cells (EC) cultured from T2DM and nondiabetic (ND) patients are
      phenotypically and functionally distinct. Cultured human saphenous vein- (SV-) EC
      were compared between T2DM and ND patients in parallel. Proliferation, migration,
      and in vitro angiogenesis assays were performed; western blotting was used to
      quantify phosphorylation of Akt, ERK, and eNOS. The ability of diabetic stimuli
      (hyperglycaemia, TNF-alpha, and palmitate) to modulate angiogenic potential of ND
      EC was also explored. T2DM-EC displayed reduced migration (~30%) and angiogenesis
      (~40%) compared with ND-EC and a modest, nonsignificant trend to reduced
      proliferation. Significant inhibition of Akt and eNOS, but not ERK
      phosphorylation, was observed in T2DM cells. Hyperglycaemia did not modify ND-EC
      function, but TNF-alpha and palmitate significantly reduced angiogenic capacity
      (by 27% and 43%, resp.), effects mimicked by Akt inhibition. Aberrancies of EC
      function may help to explain the increased risk of SV graft failure in T2DM
      patients. This study highlights the importance of other potentially contributing
      factors in addition to hyperglycaemia that may inflict injury and long-term
      dysfunction to the homeostatic capacity of the endothelium. 

PMID- 25950007
TI  - A novel multidisciplinary intervention for long-term weight loss and glycaemic
      control in obese patients with diabetes.
AB  - INTRODUCTION: Obesity and diabetes are difficult to treat in public clinics. We
      sought to determine the effectiveness of the Metabolic Rehabilitation Program
      (MRP) in achieving long-term weight loss and improving glycaemic control versus
      "best practice" diabetes clinic (DC) in obese patients using a retrospective
      cohort study. METHODS: Patients with diabetes and BMI > 30 kg/m(2) who attended
      the MRP, which consisted of supervised exercise and intense allied health
      integration, or the DC were selected. Primary outcomes were improvements in
      weight and glycaemia with secondary outcomes of improvements in blood pressure
      and lipid profile at 12 and 30 months. RESULTS: Baseline characteristics of both
      cohorts (40 MRP and 40 DC patients) were similar at baseline other than age (63
      in MRP versus 68 years in DC, P = 0.002). At 12 months, MRP patients lost 7.65 +/
      1.74 kg versus 1.76 +/- 2.60 kg in the DC group (P < 0.0001) and 9.70 +/- 2.13
      kg versus 0.98 +/- 2.65 kg at 30 months (P < 0.0001). Similarly, MRP patients had
      significant absolute reductions in %HbA1c at 30 months versus the DC group (-0.86
      +/- 0.31% versus 0.12% +/- 0.33%, P < 0.038), with nonsignificant improvements in
      lipids and blood pressure in MRP patients. CONCLUSION: Further research is needed
      to establish the MRP as an effective strategy for achieving sustained weight loss
      and improving glycaemic control in obese patients with type 2 diabetes.

PMID- 25950008
TI  - Longitudinal Analysis of Adiponectin through 20-Year Type 1 Diabetes Duration.
AB  - Little information exists on the trajectory and determinants of adiponectin, a
      possible insulin sensitizer and marker for inflammation and endothelial function,
      across the duration of type 1 diabetes. The Wisconsin Diabetes Registry Study
      followed an incident cohort <= 30 years of age when diagnosed with type 1
      diabetes during 1987-1992 up to 20-year duration. Adiponectin was concurrently
      and retrospectively (from samples frozen at -80  degrees C) measured for those
      participating in a 20-year exam (n = 304), during 2007-2011. Adiponectin levels
      were higher in females, declined through adolescence, and increased with age
      thereafter. Lower levels were associated with greater body weight and waist
      circumference and with higher insulin dose, especially at longer diabetes
      durations. Higher levels were associated with higher HbA1c and, at longer
      durations, with higher albumin-creatinine ratio. Adiponectin levels showed
      consistency within individuals that was not explained by these factors. We
      conclude that markers for insulin resistance are associated with lower
      adiponectin, and markers for potential microvascular complications are associated
      with higher adiponectin. The previously reported relationship with HbA1c remains
      largely unexplained. Additional individual specific factors likely also influence
      adiponectin level. The relationship between adiponectin and urinary protein
      excretion may enable identification of those predisposed to kidney disease
      earlier in type 1 diabetes.

PMID- 25950009
TI  - Increased DNA dicarbonyl glycation and oxidation markers in patients with type 2
      diabetes and link to diabetic nephropathy.
AB  - AIM: The aim of this study was to assess the changes of markers of DNA damage by
      glycation and oxidation in patients with type 2 diabetes and the association with
      diabetic nephropathy. METHODOLOGY: DNA oxidation and glycation adducts were
      analysed in plasma and urine by stable isotopic dilution analysis liquid
      chromatography-tandem mass spectrometry. DNA markers analysed were as follows:
      the oxidation adduct 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-OxodG) and glycation
      adducts of glyoxal and methylglyoxal--imidazopurinones GdG, MGdG, and N2-(1,R/S
      carboxyethyl)deoxyguanosine (CEdG). RESULTS: Plasma 8-OxodG and GdG were
      increased 2-fold and 6-fold, respectively, in patients with type 2 diabetes, with
      respect to healthy volunteers. Median urinary excretion rates of 8-OxodG, GdG,
      MGdG, and CEdG were increased 28-fold, 10-fold, 2-fold, and 2-fold, respectively,
      in patients with type 2 diabetes with respect to healthy controls. In patients
      with type 2 diabetes, nephropathy was associated with increased plasma 8-OxodG
      and increased urinary GdG and CEdG. In a multiple logistic regression model for
      diabetic nephropathy, diabetic nephropathy was linked to systolic blood pressure
      and urinary CEdG. CONCLUSION: DNA oxidative and glycation damage-derived
      nucleoside adducts are increased in plasma and urine of patients with type 2
      diabetes and further increased in patients with diabetic nephropathy.

PMID- 25950010
TI  - TACI expression and signaling in chronic lymphocytic leukemia.
AB  - TACI is a membrane receptor of BAFF and APRIL, contributing to the
      differentiation and survival of normal B cells. Although malignant B cells are
      also subjected on TACI signaling, there is a remarkable intradisease and
      interindividual variability of TACI expression in B-cell malignancies. The aim of
      our study was to explore the possible role of TACI signaling in the biology of
      chronic lymphocytic leukemia (CLL), including its phenotypic and clinical
      characteristics and prognosis. Ninety-four patients and 19 healthy controls were
      studied. CLL patients exhibited variable TACI expression, with the majority of
      cases displaying low to undetectable TACI, along with low to undetectable BAFF
      and increased APRIL serum levels compared to healthy controls. CLL cells with
      high TACI expression displayed a better survival capacity in vitro, when cultured
      with BAFF and/or APRIL. Moreover, TACI expression was positively correlated with
      the presence of monoclonal gammopathy and inversely with CD11c expression.
      Therefore, our study provides further evidence for the contribution of BAFF/APRIL
      signaling to CLL biology, suggesting also that TACI detection might be useful in
      the selection of patients for novel targeting therapeutic approaches. 

PMID- 25950011
TI  - Molecular Inclusion Complexes of beta-Cyclodextrin Derivatives Enhance Aqueous
      Solubility and Cellular Internalization of Paclitaxel: Preformulation and In
      vitro Assessments.
AB  - Drugs with low aqueous solubility and permeability possess substantial challenges
      in designing effective and safe formulations. Synergistic solubility and
      permeability enhancement in a simple formulation can increase bioavailability and
      efficacy of such drugs. To overcome limitations of the clinical formulation of
      Taxol(r), Paclitaxel (PTX) was reformulated with various beta-cyclodextrin (CD)
      derivatives suitable for parenteral administration. Results indicated that beta
      CDs can efficiently form complexes with PTX at lower molar ratios, enhance
      aqueous solubility up to 500 times and improved cellular internalization of PTX.
      All beta-CD derivatives were found to be safe as excipient since none showed
      detectable signs of cyto-genotoxicity. As a result, the CD-PTX complexes
      significantly increased the cytotoxicity of the drug. The study concluded that CD
      PTX formulations could substitute the current intravenous infusion of PTX
      obviating the use of non-inert excipient Cremophor EL.

PMID- 25950012
TI  - Plasmonic Films Can Easily Be Better: Rules and Recipes.
AB  - High-quality materials are critical for advances in plasmonics, especially as
      researchers now investigate quantum effects at the limit of single surface
      plasmons or exploit ultraviolet- or CMOS-compatible metals such as aluminum or
      copper. Unfortunately, due to inexperience with deposition methods, many
      plasmonics researchers deposit metals under the wrong conditions, severely
      limiting performance unnecessarily. This is then compounded as others follow
      their published procedures. In this perspective, we describe simple rules
      collected from the surface-science literature that allow high-quality plasmonic
      films of aluminum, copper, gold, and silver to be easily deposited with commonly
      available equipment (a thermal evaporator). Recipes are also provided so that
      films with optimal optical properties can be routinely obtained.

PMID- 25950013
TI  - An Optically Controlled Microscale Elevator Using Plasmonic Janus Particles.
AB  - In this article, we report how Janus particles, composed of a silica sphere with
      a gold half-shell, can be not only stably trapped by optical tweezers but also
      displaced controllably along the axis of the laser beam through a complex
      interplay between optical and thermal forces. Scattering forces orient the
      asymmetric particle, while strong absorption on the metal side induces a thermal
      gradient, resulting in particle motion. An increase in the laser power leads to
      an upward motion of the particle, while a decrease leads to a downward motion. We
      study this reversible axial displacement, including a hysteretic jump in the
      particle position that is a result of the complex pattern of a tightly focused
      laser beam structure above the focal plane. As a first application we
      simultaneously trap a spherical gold nanoparticle and show that we can control
      the distance between the two particles inside the trap. This photonic micron
      scale "elevator" is a promising tool for thermal force studies, remote sensing,
      and optical and thermal micromanipulation experiments.

PMID- 25950014
TI  - Diagrammatic analysis of nonhomogeneous diffusion.
AB  - By virtue of its complexity, realistic approaches to describe diffusion in
      cellular media require the employment of computational methods. Among others,
      this type of studies has shown that the apparent diffusion coefficient of a
      macromolecular solute through a cytoplasmic-like medium exhibits a power-law
      dependence with the excluded volume. Power laws are ubiquitous findings in
      diverse systems, such as metabolic processes, population dynamics, and
      communication networks, and have been the object of many interpretative formal
      approaches. This study introduces a diagrammatic algorithm, inspired in previous
      ones employed to analyze multicyclic chemical systems, to derive expressions for
      nonhomogeneous diffusion coefficients and to study the effects of volume
      exclusion. A most noteworthy result of this work is that midsize diagrams of
      nonhomogeneous diffusion are already able to exhibit an approximate power-law
      dependence of the diffusion coefficient with the excluded volume. The employment
      of the diagrammatic method for the analysis of simple situations may thus prove
      useful to interpret some properties of larger network systems. 

PMID- 25950016
TI  - Simulation and study of power quality issues in a fixed speed wind farm
      substation.
AB  - Power quality issues associated with the fixed speed wind farm substation located
      at Coimbatore district are investigated as the wind generators are tripping
      frequently. The investigations are carried out using two power quality analyzers,
      Fluke 435 and Dranetz PX5.8, with one of them connected at group control breaker
      of the 110 kV feeder and the other at the selected 0.69 kV generator busbar
      during the period of maximum power generation. From the analysis of the recorded
      data it is found that sag, swell, and transients are the major events which are
      responsible for the tripping of the generators. In the present study, simulation
      models for wind, turbine, shaft, pitch mechanism, induction generator, and grid
      are developed using DIgSILENT. Using the turbine characteristics, a two
      dimensional lookup table is designed to generate a reference pitch angle
      necessary to simulate the power curve of the passive stall controlled wind
      turbine. Various scenarios and their effects on the performance of the wind farm
      are studied and validated with the recorded data and waveforms. The simulation
      model will be useful for the designers for planning and development of the wind
      farm before implementation.

PMID- 25950018
TI  - Smart TV-Smartphone Multiscreen Interactive Middleware for Public Displays.
AB  - A new generation of public displays demands high interactive and multiscreen
      features to enrich people's experience in new pervasive environments.
      Traditionally, research on public display interaction has involved mobile devices
      as the main characters during the use of personal area network technologies such
      as Bluetooth or NFC. However, the emergent Smart TV model arises as an
      interesting alternative for the implementation of a new generation of public
      displays. This is due to its intrinsic connection capabilities with surrounding
      devices like smartphones or tablets. Nonetheless, the different approaches
      proposed by the most important vendors are still underdeveloped to support
      multiscreen and interaction capabilities for modern public displays, because most
      of them are intended for domestic environments. This research proposes
      multiscreen interactive middleware for public displays, which was developed from
      the principles of a loosely coupled interaction model, simplicity, stability,
      concurrency, low latency, and the usage of open standards and technologies.
      Moreover, a validation prototype is proposed in one of the most interesting
      public display scenarios: the advertising. 

PMID- 25950017
TI  - Diagnostic potential of multidetector computed tomography for characterizing
      small renal masses.
AB  - OBJECTIVES: To assess the potential of CT for characterizing small renal tumors.
      METHODS: 76 patients with <4 cm renal tumors underwent CT examination. The
      following parameters were assessed: presence of calcifications, densitometry on
      unenhanced and enhanced scans, washout percentage, urinary tract infiltration,
      star-shaped scar, and paradoxical effect. RESULTS: Calcifications were found in
      7/56 (12.5%) carcinomas. Clear cell carcinomas were as follows: mean density
      183.5 HU (arterial phase), 136 HU (portal phase), and 94 HU (delayed phase),
      washout 34.3%; chromophobe carcinomas were as follows: mean density 135 HU
      (arterial phase), 161 HU (portal phase), and 148 HU (delayed phase), washout 28%;
      papillary carcinomas were as follows: mean density 50.3 HU (arterial phase), 60
      HU (portal phase), and 58.1 HU (delayed phase), washout 2.7%. In 2/56 (3.6%)
      cases urinary tract infiltration was found. Oncocytomas were as follows: mean
      density 126.5 HU (arterial phase), 147.5 HU (portal phase), and 115.5 HU (delayed
      phase), washout 28.6%. On unenhanced scans, angiomyolipomas were as follows:
      density values <30 HU in 12/12 (100%) of cases and on enhanced scans: mean
      density 78 HU (arterial phase), 128 HU (portal phase), and 80 HU (delayed phase),
      washout 50%. CONCLUSIONS: Intralesional calcifications and urinary tract
      infiltration are suggestive for malignancy, with the evidence of adipose tissue
      for angiomyolipomas and a modest increase in density with a reduced washout for
      papillary carcinomas. The intralesional density on enhanced scans, peak
      enhancement, and washout do not seem significant for differentiating clear cell,
      chromophobe carcinomas, angiomyolipomas, and oncocytomas.

PMID- 25950015
TI  - Andrographis paniculata (Burm. f.) Wall. ex Nees: a review of ethnobotany,
      phytochemistry, and pharmacology.
AB  - As aboriginal sources of medications, medicinal plants are used from the ancient
      times. Andrographis paniculata is one of the highly used potential medicinal
      plants in the world. This plant is traditionally used for the treatment of common
      cold, diarrhoea, fever due to several infective cause, jaundice, as a health
      tonic for the liver and cardiovascular health, and as an antioxidant. It is also
      used to improve sexual dysfunctions and serve as a contraceptive. All parts of
      this plant are used to extract the active phytochemicals, but the compositions of
      phytoconstituents widely differ from one part to another and with place, season,
      and time of harvest. Our extensive data mining of the phytoconstituents revealed
      more than 55 ent-labdane diterpenoids, 30 flavonoids, 8 quinic acids, 4
      xanthones, and 5 rare noriridoids. In this review, we selected only those
      compounds that pharmacology has already reported. Finally we focused on around 46
      compounds for further discussion. We also discussed ethnobotany of this plant
      briefly. Recommendations addressing extraction process, tissue culture, and
      adventitious rooting techniques and propagation under abiotic stress conditions
      for improvement of phytoconstituents are discussed concisely in this paper.
      Further study areas on pharmacology are also proposed where needed. 

PMID- 25950020
TI  - Machine learning in intelligent video and automated monitoring.

PMID- 25950019
TI  - Dental students' knowledge of oral health for persons with special needs: a pilot
      study.
AB  - OBJECTIVES: The purpose of this pilot study was to assess the knowledge and
      awareness of dental students with respect to oral health care of the person with
      special health care needs (SHCN) and evaluate effectiveness of an education
      program on improving their knowledge. METHOD: An evaluation consisting of a
      questionnaire was answered before and immediately after a 30-minute educational
      presentation in the form of a DVD that includes a PowerPoint and a video of oral
      health care for individuals with SHCN. The questionnaire was based on the
      materials and information presented in the DVD and included 26 questions
      (true/false/I do not know). RESULTS: The mean (+/- SD) score on the pretest was
      10.85 (+/- 5.20), which increased to 16.85 (+/- 5.47) on the posttest. This
      difference was statistically significant (P < 0.001). Forty percent of the
      students surveyed reported that they were very satisfied with the educational
      part of the presentation, while 50% were somewhat satisfied. Thirty percent of
      students expressed that the educational intervention used is very effective.
      CONCLUSIONS: Viewing the educational intervention was effective in informing the
      sophomore students and providing them with instructive basic information on
      person with SHCN. Dental colleges should increase students' knowledge, training,
      and exposure to individuals with SHCN.

PMID- 25950021
TI  - Recent theories and applications in approximation theory.

PMID- 25950022
TI  - Shaping Ability of Reciproc, UnicOne, and Protaper Universal in Simulated Root
      Canals.
AB  - The study aimed to compare the shaping effects, preservation of the original
      curvature, and transportation of the apical foramen of Reciproc (VDW, Munich,
      Germany), UnicOne (Medin, Nove Mesto na Morave, Czech Republic), and Protaper
      Universal (Dentsply Maillefer, Ballaigues, Switzerland) in simulated root canals.
      Thirty resin blocks with simulated curved root canals were distributed into three
      groups (n = 10), and prepared using Reciproc (RCp), UnicOne (UnO) and the
      Protaper Universal (PTu). Standardized photographs were taken before and after
      the instrumentation, after which they were superimposed. Measurements were taken
      of the quantity of resin removed from the inner and outer walls of the curvature
      at 6 levels, the curvature angles before and after instrumentation, and the
      transportation of the apical foramen. RCp obtained the highest values for amount
      of resin removed from the inner wall while UnO demonstrated similar shaping on
      both the inner and outer walls. PTu produced the greatest transportation of
      foramen when compared to the reciprocating instruments. There was no significant
      difference between the groups in terms of the change in angle (P > 0.05). All the
      instruments were capable of maintaining the original curvature of the root canal;
      however, the UnO, which used reciprocating movement, produced more conservative
      shapes with lower foramen transportation. 

PMID- 25950025
TI  - Carphology.

PMID- 25950023
TI  - EFFECT OF LIPOSOMAL CLODRONATE-DEPENDENT DEPLETION OF PROFESSIONAL ANTIGEN
      PRESENTING CELLS ON NUMBERS AND PHENOTYPE OF CANINE CD4+CD25+FOXP3+ REGULATORY T
      CELLS.
AB  - Regulatory T cells (Tregs) are known to control autoreactivity during and
      subsequent to the development of the peripheral immune system. Professional
      antigen presenting cells (APCs), dendritic cells (DCs) and monocytes, have an
      important role in inducing Tregs. For the first time, this study evaluated
      proportions and phenotypes of Tregs in canine peripheral blood depleted of
      professional APCs, utilizing liposomal clodronate (LC) and multicolor flow
      cytometry analysis. Our results demonstrate that LC exposure promoted short term
      decreases followed by significant increases in the proportions or absolute
      numbers of CD4+CD25+FOXP3+ Tregs in dogs. In general, the LC-dependent Treg
      fluctuations were similar to the changes in the levels of CD14+ monocytes in
      Walker hounds. However, the proportions of monocytes showed more dramatic changes
      compared to the proportions of Tregs that were visually unchanged after LC
      treatment over the study period. At the same time, absolute Treg numbers showed,
      similarly to the levels of CD14+ monocytes, significant compensatory gains as
      well as the recovery during the normalization period. We confirm the previous
      data that CD4+ T cells with the highest CD25 expression were highly enriched for
      FOXP3. Furthermore, for the first time, we report that CD4+CD25lowFOXP3+ is the
      major regulatory T cell subset affected by LC exposure. The increases within the
      lowest CD25 expressers of CD4+FOXP3+ cells together with compensatory gains in
      the proportion of CD14+ monocytes during compensatory and normalization periods
      suggest the possible direct or indirect roles of monocytes in active recruitment
      and generation of Tregs from naive CD4+ T cells.

PMID- 25950024
TI  - [Author reply].

PMID- 25950026
TI  - Authors' 2015 additions to the IOC consensus statement: Relative Energy
      Deficiency in Sport (RED-S).

PMID- 25950027
TI  - Lenalidomide for myelodysplastic syndromes with del(5q): how long should it last?
AB  - Lenalidomide induces in patients with myelodysplastic syndrome (MDS) and del(5q)
      erythroid and cytogenetic response rates as high as 75% and 50%, respectively. It
      is still unclear, however, how long lenalidomide treatment should be continued
      and whether or not the drug could be interrupted. To assess the feasibility of
      lenalidomide discontinuation, we revised a cohort of 16 low-risk MDS patients
      with del(5q) treated at our institute in a phase II multicentric Italian study.
      Among the 12 responding patients, four discontinued lenalidomide while in
      complete response. All four patients needed during treatment a permanent
      lenalidomide reduction from 10 to 5 mg/day because of haematological toxicity
      (three patients) or grade 3 muscular and bone pain (one patient). At lenalidomide
      discontinuation after 16, 20, 27 and 20 months from the start, respectively, all
      four patients were in complete hematologic response and three forth in complete
      cytogenetic response. Three patients are still in response after 36, 30 and 20
      months from lenalidomide discontinuation, respectively: The remaining patient
      relapsed after 20 months, and she is now receiving a new course of lenalidomide.
      In conclusion, long-lasting remissions are achievable in MDS patients with
      del(5q) in complete response after lenalidomide discontinuation.

PMID- 25950028
TI  - Optimal loading: key variables and mechanisms.

PMID- 25950029
TI  - Exercise prescription: bridging the gap to clinical practice.

PMID- 25950030
TI  - Bloodletting for pneumonia, prolonged bed rest for low back pain, is subacromial
      decompression another clinical illusion?

PMID- 25950031
TI  - Return to play or riding the pachyderm: a call for standards based on Swiss
      values.

PMID- 25950032
TI  - Soft tissue sore spots of an unknown origin.

PMID- 25950033
TI  - Moving towards a more ecologically valid model of parent-implemented
      interventions in autism.

PMID- 25950034
TI  - Diagnosis and treatment of the patient with heart failure. What their history and
      your clinical exam should tell you about what's happening.

PMID- 25950035
TI  - Colorado consortium combines data from insurers & doctors' offices.

PMID- 25950036
TI  - [The urgent problems of the improvement of the environment management system
      based on the analysis of health risk assessment].
AB  - The lack of adequate legislative and regulatory framework for ensuring
      minimization of the health risks in the field of environmental protection is the
      obstacle for the application of the risk analysis methodology as a leading tool
      for administrative activity in Russia. "Principles of the state policy in the
      sphere of ensuring chemical and biological safety of the Russian Federation for
      the period up to 2025 and beyond", approved by the President of the Russian
      Federation on 01 November 2013, No PR-25 73, are aimed at the legal support for
      the health risk analysis methodology. In the article there have been supposed the
      main stages of the operative control of the environmental quality, which lead to
      the reduction of the health risk to the acceptable level. The further improvement
      of the health risk analysis methodology in Russia should contribute to the
      implementation of the state policy in the sphere of chemical and biological
      safety through the introduction of complex measures on neutralization of chemical
      and biological threats to the human health and the environment, as well as
      evaluation of the economic effectiveness of these measures. The primary step
      should be the legislative securing of the quantitative value for the term:
      "acceptable risk".

PMID- 25950037
TI  - [Approaches of European and Russian legislation in the field of management of
      medical waste].
AB  - A comparative analysis of Russian and European legislation concerning to the
      waste management has been performed. There were revealed principal differences in
      Russian and European legislation in methodology of the waste classification. In
      Europe, there is no methodology for breaking up waste into hazard classes, and
      for the denomination of the danger there are used hazard lists which fail to give
      information about the extent of their danger. Medical waste in the European
      legislation are not selected into the separate category as being included in
      terms of articles and lists in the annexes to the directives or other legal acts.
      There are considered requirements of the Russian and European legislation in the
      area of the landfill waste burial. In the frameworks of the proposals for the
      implementation of international experience in the waste management there was
      drafted the project of Sanitary rules on hygiene requirements to the arrangement
      and the contents of landfills for residential solid waste, which includes
      requirements concerning not only residential solid waste, but also medical waste.

PMID- 25950038
TI  - [Scientific substantiation of hygienic criteria for sanitary-epidemiological
      assessment of chemical water disinfectants].
AB  - In the article there are considered the approaches to the hygienic assessment of
      efficacy and safety of chemical water disinfectants. On the basis of the own
      research of efficiency, with taking into account the reactivation of
      microorganisms, toxicity, impurity content, the processes of transformation of
      disinfectants, as well as the literature data there were developed the sanitary
      epidemiological criteria for the assessment of the efficacy and safety of water
      disinfectants. These criteria include: the intensity of efficiency and time of
      exposure, the degree of universality of the action in relation to microorganisms,
      afteraction, lack of promoting of microorganisms tolerance, the ability to comply
      with the MPC after disinfection, the impact on the organoleptic properties of
      water, the probability of formation of hazardous transformation products in
      water, the presence of available and selective method for the determination in
      water, the possibility of neutralization, safety in use, transportation, storage.

PMID- 25950039
TI  - [Environmental pollution by products of wear and tear automobile-road complex].
AB  - North-West State Medical University named after I.I. Mechnikov, Saint Petersburg,
      Russian Federation, 191015. There is supposed the method for the assessment of
      amounts of pollutants released into the environment during the operational wear
      of tyre treads, brake system of cars and the road pavement. There are presented
      results of chemical analysis of residues of combustion. The necessity of control
      of products of work wear of automobile-road complex has been substantiated.

PMID- 25950040
TI  - [Hygienic characteristics of the quality OF underground drinking water in oil
      producing areas].
AB  - The purpose of the research was the assessment and the disclosure of the features
      of the pollution of groundwater at the oil-producing areas of the Republic of
      Bashkortostan and the elaboration of hygienic recommendations for environmentally
      sound water management. According to results of the studies performed there is
      presented the characteristic of main reasons leading to the pollution of
      groundwater in the location of oil and gas producing regions There was suggested
      the complex of hygienic recommendations and management decisions on the
      improvement of the water supply in areas with advanced oil production.

PMID- 25950041
TI  - [Neuropsychic development in preschool children in conditions of the
      informatization].
AB  - The new millennium was marked by the transition of humanity to a new stage of the
      development--the Information Society, which is an objective reality and affects
      on all aspects of living environment, including the health of children. The last
      decade was characterized by the increase of the use of means of informatization,
      the level of aggression and aggressiveness of children, the decrease of
      intellectual indices, deterioration of mental health, an increase of children
      with behavioral problems, hyperactivity, inattention, decrease of mental
      capacity. In a study on the example of preschool educational institution in the
      city of Irkutsk in the conditions of the changing of the informatization level of
      the society in the time period from 1998 to 2012, there were revealed the changes
      in indices of intellectual development, mental capacity and anxiety of children.
      Under observation there were 211 children aged from 5.5 to 6.5 years in the
      preschool institution of the central district of the city of Irkutsk. There were
      formed two groups of children: I group--children who attended kindergarten in
      1998 and group II--children attending kindergarten in 2012. Age groups of
      preschool children were consistent with their calendar age: from 5 years 5 months
      30 days to 6 years 5 months 30 days. In the study of intellectual development
      there has been shown the decrease of the number of children with average
      intelligence level and an increase in children with the below-average
      intelligence level, the increase of the speed (p < 0.05.) and the decrease of the
      quality (p < 0.05.) of the information processing in the Anfilov test for the
      mental performance and the increase the general level of anxiety, aggressive
      background and unmotivated fears "out" at the present time stage (2012).

PMID- 25950042
TI  - [The content of heavy metals in soils of the Yamal Peninsula and thE Bely
      Island].
AB  - In 2012 for the first time the Government of the Yamal-Nenets region in
      conjunction with the Arctic and Antarctic Research Institute of RosHydromnet,
      performed the first comprehensive expedition for the examination of the Yamal
      Peninsula (KAEMB Arctic Yamal-2012). As key observation plots there were
      selected: settlement Novy Port, Ust Yuribey and the Island Bely. To the last
      section now there is attracted the maximum attention of the public, because it is
      selected for the starting of the program for the cleaning up Arctic from the
      debris and the wastes accumulated during the process of the functioning of polar
      infrastructure. Soil samples were selected from the prospecting pits in August,
      2012. Heavy metals, as well as the content of oxides of silicon, aluminum, iron,
      titanium, manganese were detected with X-ray fluorescent analyzer "Spectroscan
      MAX. The values obtained were compared with thre Approxible Permissible
      Concentrations and Maximum Allowable Concentrations adopted in Russia. Since the
      accumulation of heavy metals is related with their fixation by soil organic
      matter, concomitantly there was evaluated the content of organic carbon and
      nitrogen with the use of the device VARIO EL III. The application of the profile
      approach to the study of the chemical composition of soils helped to establish
      mid-ground and deep supra permafrost accumulation maximums of priority inorganic
      toxicants and other heavy metals. This is most likely related to the development
      of two groups of soil processes: eluvial-illuvial and cryogenic mass exchange. As
      a result of the eluvial-illuvial processes, some heavy metals are redistributed
      along the profile, and accumulating in the middle part of the profile. Meanwhile,
      in the tundra soils dominant processes are cryogenic mass exchange, leading to a
      strong mixing of the soil column and the accumulation of certain components in
      the chemical composition in the supra permafrost or surprapermafrost-gley
      horizon. This is the main reason for the second peak of the content of heavy
      metals in the bottom of the soil profiles. Performed studies show that although
      most heavy metals are accumulated in the upper soil horizons, in the case of
      tundra, soil profile redistribution processes lead to the fact that in the case
      of the surface sampling, there is underestimation of the total reserves of
      substances in the soil profile.

PMID- 25950043
TI  - [Features of the dynamics of the state of health of the population residing near
      fuel and energy complex of the Republic of Kazakhstan].
AB  - There was performed the analysis of the state of health of the population
      residing near fuel and energy complex of the Republic of Kazakhstan in the
      vicinity of the fuel and energy complex of Kazakhstan, namely, of the
      Lebyazhinsky district of the Pavlodar region. The chemicals contained in the
      emissions of existing enterprises of the fuel and energy complex, have a direct
      impact on public health. There is noted an increase of some diseases such as
      respiratory diseases, complications of pregnancy, childbirths and the postpartum
      period, diseases of the nervous system, mental and behavioral disorders,
      neoplasms. The child population is particularly prone to the impact of air
      pollutants. In children from the studied area every year the incidence of asthma
      is increasing by 3 times, the incidence of neoplasms--by 2 times.

PMID- 25950044
TI  - [Rationale for the permissible level of carbon dioxide in indoor air in
      residential and public buildings with the permanent human presence].
AB  - On the base of the analysis of domestic and foreign data on the issue of rating
      of carbon dioxide in the indoor air of residential and public buildings and
      results of own research there is justified an permissible level of carbon dioxide
      in the indoor air of residential and public buildings with a permanent human
      presence. The concentration of carbon dioxide in the air space, not higher 1000
      ppm (0.1%) was established to have no negative impact on the human health and
      performance, with this content of carbon dioxide there is no accumulation of
      toxic chemicals and registered by devices reducing of the oxygen content in the
      air of spaces, it meets the regulatory requirements for content dioxide carbon in
      the indoor air, applicable in most of foreign countries.

PMID- 25950045
TI  - [On the rating of Helicobacter pylori in drinking water].
AB  - There are considered the issues related to the possibility to rate of
      Helicobacter pylori (H. pylori) content in drinking water. There is described the
      mechanism of of biofilm formation. The description refers to the biofilm
      formation mechanism in water supply systems and the existence of H. pylori in
      those systems. The objective premises of the definition of H. pylori as a
      potential limiting factor for assessing the quality of drinking water have been
      validated as follows: H. pylori is an etiologic factor associated to the
      development of chronic antral gastritis, gastric ulcer and duodenal ulcer, and
      gastric cancer either, in the Russian population the rate of infection with H.
      pylori falls within range of 56 - 90%, water supply pathway now can be considered
      as a source of infection of the population with H. pylori, the existence of WHO
      regulatory documents considering H. pylori as a candidate for standardization of
      the quality of the drinking water quite common occurrence of biocorrosion, the
      reduction of sanitary water network reliability, that creates the possibility of
      concentrating H. pylori in some areas of the water system and its delivery to the
      consumer of drinking water, and causes the necessity of the prevention of H.
      pylori-associated gastric pathology of the population. A comprehensive and
      harmonized approach to H. pylori is required to consider it as a candidate to its
      rating in drinking water. Bearing in mind the large economic losses due to, on
      the one hand, the prevalence of disease caused by H. pylori, and, on the other
      hand, the biocorrosion of water supply system, the problem is both relevant in
      terms of communal hygiene and economy.

PMID- 25950046
TI  - [Study of cytogenetic and cytotoxic effect of non-contact electrochemically
      activated waters in the five organs of rats].
AB  - For the first time the multiorgan karyological analysis of five organs of rats
      was applied for the study of the cytogenetic and cytotoxic action of the four
      types of non-contact electrochemically activated water in the 30-days in vivo
      experiment. The effects of investigated waters were not detected in bone marrow
      polychromatic erythrocytes. "Anolyte" (ORP = -362 mV) did not have a negative
      effect on rats. "Catholyte-5" (ORP = +22 mV) and "Catholyte-25" (ORP = -60 mV)
      induced cytogenetic abnormalities in the bladder and fore stomach. The same
      catholytes and "Catholyte-40" (ORP = -10 mV) changed the proliferation indices:
      increased the mitotic index in the fore stomach epithelium and reduced the
      frequency of binucleated cells in the fore stomach, bladder and lungs. The
      increase in the rate of cells with cytogenetic abnormalities on the background of
      the promotion of mitotic activity can be considered as a manifestation of the
      negative effect, typical for catolytes, but the effect of each out of them has
      its own features.

PMID- 25950047
TI  - [Methodical approaches to the substantiation of hygienic requirements for the
      application of deicing materials].
AB  - In the paper there is presented a review of existing guidelines and rules of
      operation of deicing materials (DIM), as well as opportunities for their
      processing with the aim to ensure the security for the environment and public
      health. There are described the ecological- hygienic and toxicological properties
      of chemicals. There are reported results of a pot experiment for the assessment
      of the impact of DIM on the lawn.

PMID- 25950048
TI  - [The combined effect of lead and zinc on the embryonic development of laboratory
      rats].
AB  - In the article there are presented the results of the study of the impact of
      inorganic lead and zinc compounds, as well as their organic forms produced with
      the use of nanotechnoloy, on the embryonic development of laboratory rats. Metals
      were orally administered daily during 19 days of gestation at the doses of 0.05
      mg/kg of lead, and 1.5 mg/kg of zinc. The impact of the test substances was
      evaluated by integral and specific indices with the use of physiological,
      morphological and quantitative methods of analysis. Lead in a dose of 0.05 mg/kg
      was established to disturb the antenatal development of the offspring of
      experimental animals, which is pronounced in the increased embryo lethality rate,
      deterioration of somatometric indices of male fetuses in the litter as compared
      with the control group, and compared with females. In permits to suggest the
      greater sensitivity of male fetuses to exposure to lead. The isolated impact of
      zinc in the dose of 1.5 mg/kg body weight does not influence on the levels of
      embrio mortality rate, as well as somatometric indices of fetuses. However, the
      combined administration of the compounds of zinc and lead weakens the embryotoxic
      effect of the latter in terms of embrio lethality and the amount of live fetuses
      in the litter with more effective bioprotection for zinc in the nanoaquachelate
      form.

PMID- 25950049
TI  - [Designing of laboratories is crucial for the management of biorisks in the work
      with pathogenic biological agents].
AB  - Currently in the Russian Federation there is planned the reconstruction and
      construction of new facilities tailored for the work with pathogenic biological
      agents of I-II pathogenicity groups, with bearing in mind the modern level of the
      development of equipment and technologies technological. However, in Russia there
      is no specialized institutions for the designing of such facilities. There were
      developed "Guidelines for the designing of objects of the Medical Sanitary Unit
      No164, tailored for the work with pathogenic biological agents of I-II
      pathogenicity groups", in which there were taken into account the requirements of
      modern Russian regulations in the field of biosafety air purification, fire
      safety.

PMID- 25950050
TI  - [Comparative analysis of the incidence of toxocariasis in 2011-2012].
AB  - According to official statistics data, and the archives' data of the specialized
      clinical diagnostical laboratory for parasitic diseases of the Clinical Center of
      the I. M. Sechenov First Moscow State Medical University in 2011 and 2012, the
      incidence of toxocariasis in Russia remains to be high and stable, because of the
      inefficiency of performed preventive measures.

PMID- 25950051
TI  - [Features of local variants of population health in the territory of Irkutsk
      region according to indices of risk for morbidity].
AB  - Regional features of population health are formed under the influence of natural
      and anthropogenic loads. The improvement of the quality of life of the population
      depends on the effectiveness of performed preventative measures that are carried
      out with taking into account the features of the territories. Proposed approach
      for the detection of the local variants of population health with the aid of the
      method of estimation of the relative risk of morbidity allows to determine the
      features of population health (according to the number of leading ecodependent
      classes of diseases with enhanced and high risk for the incidence) in industrial
      and non-industrial areas and priorities among them, requiring preventive measures
      on the improvement of the level of population health and advancement of the
      quality of life of the population.

PMID- 25950053
TI  - [Monitoring and assessment contamination of toxic elements food in Tatarstan
      monitoring and evaluation of contamination by toxic elements of food products in
      the territory of the Republic of Tatarstan].
AB  - Actual consumption of toxic elements in the body of an adult human in the
      Republic of Tatarstan (during the period of the study of the production in 2008
      2012) amounts for lead: 0.68 mg/week for cadmium: 0.18 mg/day, arsenic: 0.68
      mg/day, mercury: 0.21 mg/week (per 1 kg body weight) or respectively: 22.81%,
      18.0%, 13.69%, 4.27% of the allowable levels of the chemical load. We have
      performed calculations with account of the balance of food resources per capita
      per year in the Republic of Tatarstan. This analysis showed that the main dietary
      sources of income for cadmium there are milk and dairy products (48.32%), bakery
      products (16.07%), meat and meat products (13.22%); for lead there are bakely
      products (26.85%), potatoes (24.36%), milk and dairy products (23.94%), meat and
      meat products (7.55%); for mercury there are milk and dairy products (53.72%),
      meat and meat products (16.82%), potatoes (10.92%); fish and fish products
      (4.74%); for arsenic there are milk and dairy products (72.51%), meat and meat
      products (12.8%), bakery products (3.05% ,); fish and fish products (2.23%). It
      is important to know not only what products are the most contaminated, but what
      place in the structure of the nutrition they take.

PMID- 25950052
TI  - [Scientific substantiation of perfection of sanitary bacteriological monitoring
      in drinking water use].
AB  - Criterion of the epidemic safety of drinking water is the absence of pathogenic
      and potentially pathogenic microorganisms. Currently, water quality control is
      performed in terms of the index of total coliform bacteria (TCB). TCB index
      oriented to the labile lactose sign has not sufficient relevance in the
      determination of the degree of the epidemic danger in the water use in relation
      to Salmonella and potentially pathogenic microorganisms. The frequency of
      detection of GCB in standard quality of drinking water as well as the application
      of the methodology for the assessment of the microbial risk of the occurrence of
      bacterial intestinal infections with the use of integral index--GCB, provide the
      most reliable prediction of risk in the occurrence of water-caused intestinal
      infections and more objectively reflect the epidemiological importance of
      drinking water in their distribution among the population. Proceeding from the
      data obtained, it is advisable to carry out the quality control of drinking water
      with the use of the broader indicator index GCB- detected from basic signs of the
      Enterobacteriaceae family--glucose fermentation and oxidase test and oxidase
      test.

PMID- 25950054
TI  - [Prevention of pyloric H. pylori infection is the actual problem of modern
      preventive health care].
AB  - In the article there are presented data on the high prevalence of Helicobacter
      pylori (H. pylori) infection in Russia and its consequences, including the
      development of gastric cancer. There is presented the evidence of possible
      transmission of H. pylori with water previously underestimated. There is
      substantiated the necessity of preventing infection, which should include the
      informing of the population, compliance with hygiene standards and widespread
      availability of safe water.

PMID- 25950055
TI  - ["Big data"--the progress of hygiene science and practice: evaluation of child
      and adolescent health in Russian regions].
AB  - Theee has been analyzed information of Federal statistics agency for the period
      from 2007 to 2011 about the distribution of children in health groups, child
      morbidity and disability in view of all Russian regions. Indices are juxtaposed
      together in the course of the use of an author's technique "percentile-profile"
      that gives an evident imagination of the place of the each region according to
      the each index in the general assembly of Russian regions, about the quality of
      information on both children's health, and dispensary work and availability of
      the medico-social care for children (in determination of disability). In the
      course of the cluster analysis there were selected leading tendencies in the
      sphere of children's health on Russian territory.

PMID- 25950056
TI  - [The impact of the chemical factor on children's health with account of the early
      stages of ontogenesis].
AB  - The study was performed in three towns of the Irkutsk region. For the study the
      dependence of the "chemical load in the different periods of ontogeny--the health
      of children" there were formed 4 groups according to the place of the work of
      parents (wood chemical manufacturing, alumimum plant, petrochemical plant,
      chemical plant) and 2 control groups with account of the place of residence of
      children (in areas with high and with moderate levels of ambient air pollution).
      The rate of the primary morbidity and chronic pathology morbidity of the upper
      respiratory tract in children were established to be dependent on the direct and
      indirect (at the early stages of ontogeny) the impact of the chemical factor.

PMID- 25950057
TI  - [Assessment of the impact of environmental factors on the morbidity rate of
      respiratory and cardiovascular diseases in adolescents of the city of Samara].
AB  - There were investigated the dynamics of the level of general and primary
      morbidity rate of respiratory, diseases and cardiovascular diseases in
      adolescents in the city of Samara and the relationship of these classes of
      diseases with the soil pollution by heavy metals in the area of the Promyshlenny
      district of the city. There was noted a marked rise of the level of primary and
      total morbidity on studied classes of diseases. There were revealed the moderate
      relationship between the content of copper and cadmium in the soil and the
      morbidity in adolescents in the studied area.

PMID- 25950058
TI  - [Antioxidant system as a perspective direction in the assessment of the state and
      prognosis of population health].
AB  - The study of blood serum of persons falling under the category of people with
      high and very high physical activity, revealed the increase of the production of
      the stress hormone cortisol, that indicates to the prevalence of catabolic
      processes in the body, the decrease in saturation with zinc, copper, iron,
      disturbing the activity of enzyme link, and the reduction of the saturation of
      the body with vitamins A and E that causes the deterioration of the state of low
      molecular link of antioxidant protection. Significant physical loads contributed
      to the accumulation of lipid peroxidation products, by leading to oxidative
      stress, which was an adverse predictor of health. The obtained data prove that
      the indices of the state of the antioxidant system are a marker of health and
      criteria of population life quality.

PMID- 25950059
TI  - [Methodological approaches to the experimental study of the impact of
      environmental pollution on the human body].
AB  - In the materials there are presented features of methodological approaches in the
      performing of experimental studies concerning of the investigation of the impacts
      of environmental factors on the human body. There were shown the results of our
      experiments performed at the Institute, in the modeling of biological effects of
      antimicrobial nanobiocomposites with nanosilver particles, toxic encephalopathy,
      in the study of the combined effect of the factors of biological and chemical
      nature. There was proved the importance of intracellular of proteomics in the
      assessment of the effects of the action of nanoparticles and nanomaterials on the
      body. There were revealed key parts of progredient course of mercury poisoning in
      the long-term. The special section is presented by the study of long-term effects
      of anthropogenic environmental factors on subsequent generations. There are
      presented results witnessing to a deterioration of the functional state of the
      central nervous system in rats in the first and second generations, whose parents
      were exposed to neurotoxicants. There was proved the aggravating role of prenatal
      hypoxia in the development of toxicity in rats in sexually mature age.
      Experimental biomodeling is aimed at sighting of pathogenetically substantiated
      treatment and preventive measures: initially, in experimental conditions, and in
      the future in the rehabilitation of sick or injured patients.

PMID- 25950060
TI  - [Mathematical modeling for conditionality of cardiovascular disease by housing
      conditions].
AB  - There was studied the influence of living conditions (housing area per capita,
      availability of housing water supply, sewerage and central heating) on the
      morbidity of the cardiovascular diseases in child and adult population. With the
      method of regression analysis the morbidity rate was established to significantly
      decrease with the increase in the area of housing, constructed models are
      statistically significant, respectively, p = 0.01 and p = 0.02. There was
      revealed the relationship of the morbidity rate of cardiovascular diseases in
      children and adults with the supply with housing central heating (p = 0.02 and p
      = 0.009).

PMID- 25950061
TI  - [Scientific and methodological approaches to the organization of the preventive
      care for children with respiratory diseases associated with the exposure to
      chemical factors].
AB  - There are presented directions of the improvement of strategic approaches to the
      prevention of respiratory diseases associated with exposure to chemical
      environmental factors in children. There were substantiated principles of
      construction of health-preventive technologies, target groups, hygienic and
      clinical criteria for their formation, volumes and forms of implementation,
      targeted indices of efficacy.

PMID- 25950062
TI  - [Modern trends of preventive work in educational institutions].
AB  - In the national strategic documents of the Russian Federation's leading
      destination for health development in the coming years is preventive. In this
      connection it seems to be necessary to study the causes of the impairment of the
      formation of morphological and functional indices in today's schoolchildren, the
      establishment of controlled factors in educational institutions and the
      substantiation of the system of preventive measures for children and adolescents.
      The performed study of the physical development of Moscow schoolchildren revealed
      the discoordination of the morphofunctional development. Besides that there were
      revealed factor-forming morphofunctional state in children and adolescents. The
      results of performed studies allowed us to formulate preventive recommendations
      aimed at optimization of the morphofunctional state of the organism of
      schoolchildren.

PMID- 25950063
TI  - [The impact of nutrient prosperity of the body on the alimentary status of junior
      high school pupils within the framework of the implementation of health-saving
      technologies].
AB  - In the work there was performed the assessment of the actual nutrition of high
      school pupils, its impact on the nutritional status and efficiency of the
      implementation in the modern educational process certified vitamin-mineral
      complexes as a health-saving component of the optimization of rations. The
      introduction of additional vitamin-mineral complexes into the food of high school
      pupils was established to lead to the optimization of nutrition content by most
      of macro- and micronutrients, which in turn contributed to the increase in the
      number of children with an adequate supply of the body with vitamins and also
      contributed to the increase of students with a satisfactory adaptation by 44.3%,
      cases having sufficient performance reserves by 48.4% and the decrease of the
      number of children with sharply reduced functional reserves by 4 times.

PMID- 25950064
TI  - [New methodical approaches in the projection of zones of sanitary protection of
      water sources].
AB  - In the projection of sanitary protection zones of water sources it is extremely
      important to determine the specific boundaries of the established zones of
      sanitary protection due to the solution of property issues and responsibilities.
      In the paper projection of data with account of required scaling it is not
      possible to do. In this case, the use of geographic information systems is
      appropriate and useful. In addition there is necessary an adjustment of the
      existing sanitary calculations in relation to zones of sanitary protection of
      water sources in the part of specification of the order of approval of projects
      of sanitary protection zones and organization of the control for their
      implementation.

PMID- 25950065
TI  - [Cellular communication and health. Electromagnetic environment. Radiobiology and
      hygiene problems. Forecast of danger].

PMID- 25950066
TI  - [The balance of the Work of Plenum of the Research Council on Human Ecology and
      Environmental Hygiene of the Russian Federation "priorities of preventive health
      care in the sustainable development of society: state and approaches for the
      solution of problems"].

PMID- 25950081
TI  - "No man is an island": Effects of interpersonal proximity on spatial attention.
AB  - While it is generally acknowledged that another person's presence can influence
      how we behave within our environment, our understanding of the mechanisms
      underlying this influence is limited. Three experiments investigated the effect
      of social presence on the lateral distribution of spatial attention. Shifts in
      spatial attention were measured using line bisection, while participants sat in
      each other's personal space. An attentional withdrawal was observed, whereby
      attention moved away from the other person when the same task was using turn
      taking (Experiment 1) and independent responding (Experiment 2) paradigms. When
      participant pairs engaged in different tasks (Experiment 3), attentional
      withdrawal was no longer observed. Our results strongly suggest that the
      influence of interpersonal proximity on attention merits greater consideration
      than it has received from researchers investigating social effects on cognition.

PMID- 25950082
TI  - Enhancement of spin-wave nonreciprocity in magnonic crystals via synthetic
      antiferromagnetic coupling.
AB  - Spin-wave nonreciprocity arising from dipole-dipole interaction is insignificant
      for magnon wavelengths in the sub-100 nm range. Our micromagnetic simulations
      reveal that for the nanoscale magnonic crystals studied, such nonreciprocity can
      be greatly enhanced via synthetic antiferromagnetic coupling. The nonreciprocity
      is manifested as highly asymmetric magnon dispersion curves of the magnonic
      crystals. Furthermore, based on the study of the dependence of the nonreciprocity
      on an applied magnetic field, the antiparallel alignment of the magnetizations is
      shown to be responsible for the enhancement. Our findings would be useful for
      magnonic and spintronics applications. 

PMID- 25950083
TI  - Morbidity associated with episiotomy in vacuum delivery: a systematic review and
      meta-analysis.
AB  - BACKGROUND: The role of episiotomy in vacuum deliveries is controversial.
      OBJECTIVES: To perform a meta-analysis of the literature examining this subject.
      SEARCH STRATEGY: The search was conducted in four databases. SELECTION CRITERIA:
      Two investigators independently selected original research examining the effects
      of episiotomy on any neonatal and maternal outcomes during vacuum delivery. DATA
      COLLECTION AND ANALYSIS: The effect estimates were presented as odds ratios (ORs)
      with 95% confidence intervals (95% CIs). MAIN RESULTS: Fifteen articles were
      included, encompassing a total of 350 764 vacuum deliveries. A non-significant
      relationship was shown between mediolateral episiotomy and obstetric anal
      sphincter injuries (OASIS) in nulliparous women (OR 0.68, 95% CI 0.43-1.07; six
      studies), whereas an increased risk was demonstrated in parous women (OR 1.27,
      95% CI 1.05-1.53; two reports). A higher risk of OASIS with median episiotomy use
      was shown in nulliparous (OR 5.11, 95% CI 3.23-8.08; two studies) as well as in
      parous (OR 89.4, 95% CI 11.8-677.1; one study) women. Lateral episiotomy was
      related to lower OASIS risk in nullipara (OR 0.59, 95% CI 0.49-0.70; single
      paper). Mediolateral episiotomy was linked to increased rates of postpartum
      haemorrhage (OR 1.82, 95% CI 1.16-2.86) and analgesia use (OR 2.10, 95% CI 1.39
      3.17; two reports). Overall, the quality of evidence was rated as low to very
      low. AUTHOR'S CONCLUSIONS: Mediolateral and median episiotomy in parous woman may
      increase the rate of OASIS at vacuum delivery, whereas lateral episiotomy in
      nulliparous women could be associated with a decreased risk of OASIS. The
      suboptimal quality of the available evidence necessitates high-quality well
      designed randomised trials. TWEETABLE ABSTRACT: Episiotomy in vacuum delivery
      does not appear to be of benefit, and might even increase maternal morbidity.

PMID- 25950084
TI  - Somatostatin Agonist Pasireotide Promotes a Physiological State Resembling Short
      Day Acclimation in the Photoperiodic Male Siberian Hamster (Phodopus sungorus).
AB  - The timing of growth in seasonal mammals is inextricably linked to food
      availability. This is exemplified in the Siberian hamster (Phodopus sungorus),
      which uses the annual cycle of photoperiod to optimally programme energy
      expenditure in anticipation of seasonal fluctuations in food resources. During
      the autumn, energy expenditure is progressively minimised by physiological
      adaptations, including a 30% reduction in body mass, comprising a reduction in
      both fat and lean tissues. However, the mechanistic basis of this adaptation is
      still unexplained. We hypothesised that growth hormone (GH) was a likely
      candidate to underpin these reversible changes in body mass. Administration of
      pasireotide, a long-acting somatostatin receptor agonist developed for the
      treatment of acromegaly, to male hamsters under a long-day (LD) photoperiod
      produced a body weight loss. This comprised a reduction in lean and fat mass,
      including kidneys, testes and brown adipose tissue, typically found in short-day
      (SD) housed hamsters. Furthermore, when administered to hamsters switched from SD
      to LD, pasireotide retarded the body weight increase compared to vehicle-treated
      hamsters. Pasireotide did not alter photoperiod-mediated changes in hypothalamic
      energy balance gene expression but altered the expression of Srif mRNA expression
      in the periventricular nucleus and Ghrh mRNA expression in the arcuate nucleus
      consistent with a reduction in GH feedback and concurrent with reduced serum
      insulin-like growth factor-1. Conversely, GH treatment of SD hamsters increased
      body mass, which included increased mass of liver and kidneys. Together, these
      data indicate a role for the GH axis in the determination of seasonal body mass
      of the Siberian hamster. 

PMID- 25950085
TI  - The Interplay Between miR-148a and DNMT1 Might be Exploited for Pancreatic Cancer
      Therapy.
AB  - We discovered the expression level of miR-148a significantly decreased in
      pancreatic cancer tissues whereas that of DNMT1 increased. In ASPC-1 cancer
      cells, the overexpression of miR-148a led to a decreased level of DNMT1 and
      reduced the proliferation and metastasis of ASPC-1 cells. Moreover, the increased
      expression of miR-148a arrested the UTR methylation of p27, giving rise to an
      increased level of p27. Interestingly, it was shown that the DNMT1 inhibition
      enhanced the expression of miR-148a. In vivo studies demonstrated that the
      tumorigenesis of ASPC-1 was significantly arrested by either the overexpression
      of miR-148a or the inhibition of DNMT1. 

PMID- 25950086
TI  - Deproteinized bovine bone in association with guided tissue regeneration or
      enamel matrix derivatives procedures in aggressive periodontitis patients: a 1
      year retrospective study.
AB  - OBJECTIVES: To retrospectively evaluate and compare two regenerative periodontal
      procedures in young individuals with aggressive periodontitis (AgP). METHODS:
      Thirty-two patients aged 14-25 years (mean +/- SD 19.3 +/- 5.7) were diagnosed as
      having AgP with multiple intra-bony defects (IBDs) and treated by one of two
      regenerative modalities of periodontal therapy: guided tissue regeneration (GTR)
      using deproteinized bone xenograft (DBX) particles and a resorbable membrane (the
      GTR group), or an application of enamel matrix derivatives (EMD) combined with
      DBX (the EMD/DBX group). Periodic monitoring of treated sites included recording
      of probing depth (PD), clinical attachment level (CAL) and gingival recession.
      Pre-treatment and 1-year post-operative findings were statistically analysed
      within and between groups. RESULTS: The PD and CAL values decreased significantly
      with time, but not those between study groups. The mean pre-treatment and 1-year
      post-treatment PDs of the IBDs of the GTR group (n = 16; sites = 67) were 8.93 +/
      1.14 mm and 3.58 +/- 0.50 mm, respectively, and the mean CALs were 9.03 +/- 1.03
      mm and 4.16 +/- 0.53 mm respectively. The mean PDs of the EMD/DBX group (n = 16;
      sites = 73) were 8.77 +/- 1.04 mm and 3.61 +/- 0.36 mm, respectively, and the
      mean CALS were 8.79 +/- 1.04 mm and 3.77 +/- 0.22 mm respectively (p < 0.001 for
      all). CONCLUSION: Surgical treatment of AgP patients by either GTR or by
      application of EMD/DBX yielded similarly successful clinical results at 1-year
      post-treatment.

PMID- 25950088
TI  - Adrenal Suppression in Children Treated With Oral Viscous Budesonide for
      Eosinophilic Esophagitis.
AB  - We sought to determine the prevalence of adrenal suppression (AS) in children
      with eosinophilic esophagitis treated with oral viscous budesonide (OVB). This
      was a retrospective review of a quality assurance initiative, whereby all
      children in our center treated with OVB for >=3 months were referred over an 18
      month time frame for endocrine assessment including 1 MUg adrenocorticotropic
      hormone stimulation test. Fourteen of 19 children complied with the referral; of
      these 14 children, 6 (43%) had suboptimal stimulated cortisol (range 343-497
      nmol/L, mean [+/-SD] 424.7 nmol/L [+/-52.4], normal >=500 nmol/L). There was no
      significant association to treatment duration, dose, or concomitant use of
      inhaled/nasal corticosteroids. This study suggests that children treated with OVB
      may be at risk for AS. 

PMID- 25950087
TI  - Influence of neighbourhood-level crowding on sleep-disordered breathing severity:
      mediation by body size.
AB  - Neighbourhood-level crowding, a measure of the percentage of households with more
      than one person per room, may impact the severity of sleep-disordered breathing.
      This study examined the association of neighbourhood-level crowding with apnoea
      hypopnoea index in a large clinical sample of diverse adults with sleep
      disordered breathing. Sleep-disordered breathing severity was quantified as the
      apnoea-hypopnoea index calculated from overnight polysomnogram; analyses were
      restricted to those with apnoea-hypopnoea index >=5. Neighbourhood-level crowding
      was defined using 2000 US Census tract data as percentage of households in a
      census tract with >1 person per room. Multivariable linear mixed models were fit
      to examine the associations between the percentage of neighbourhood-level
      crowding and apnoea-hypopnoea index, and a causal mediation analysis was
      conducted to determine if body mass index acted as a mediator between
      neighbourhood-level crowding and apnoea-hypopnoea index. Among 1789 patients (43%
      African American; 68% male; 80% obese), the mean apnoea-hypopnoea index was 29.0
      +/- 25.3. After adjusting for race, age, marital status and gender, neighbourhood
      level crowding was associated with apnoea-hypopnoea index; for every one-unit
      increase in percentage of neighbourhood-level crowding mean, the apnoea-hypopnoea
      index increased by 0.40 +/- 0.20 (P = 0.04). There was a statistically
      significant indirect effect of neighbourhood-level crowding through body mass
      index on the apnoea-hypopnoea index (P < 0.001). Neighbourhood-level crowding is
      associated with severity of sleep-disordered breathing. Body mass index partially
      mediated the association between neighbourhood-level crowding and sleep
      disordered breathing. Investigating prevalent neighbourhood conditions impacting
      breathing in urban settings may be promising. 

PMID- 25950089
TI  - School Attendance in Children With Functional Abdominal Pain and Inflammatory
      Bowel Diseases.
AB  - OBJECTIVE: Inflammatory bowel disease (IBD) and functional abdominal pain (FAP)
      are associated with debilitating symptoms and frequent medical visits that may
      disrupt school functioning. The aim of this study was to assess school-related
      quality of life and school absenteeism in children with IBD, compared with FAP
      and healthy controls. METHODS: School absenteeism and participation in school and
      after-school activities data were obtained for 43 children with Crohn disease
      (CD), 31 children with ulcerative colitis (UC), 42 children with FAP, and 30 age
      matched healthy controls for the 2013-2014 school year. We used a semistructured
      questionnaire for both children and parents. For diminishing recall bias,
      absenteeism data were cross-matched with the patient's school annual report
      cards. RESULTS: Children with FAP, CD, and UC missed significantly more school
      days than age-matched healthy controls (17.6 [8.75-30], 24 [14-30], and 21 [12
      25] vs 5.1 [3.75-6.25], respectively, P < 0.001). Compared with children with
      FAP, absenteeism because of medical appointments and hospitalization was
      significantly greater in children with CD and UC (8.8 [4-14] and 7.1 [3-10] vs
      4.4 [2-6.25], P = 0.001). Participation of children with FAP and IBD in various
      school and after-school activities was significantly reduced compared with
      healthy controls. There was no difference in school attendance and functioning
      between children with IBD and FAP. CONCLUSIONS: FAP has a significant impact on
      school attendance and functioning similar to IBD. These findings show that
      significant psychosocial and academic difficulties are faced not only by children
      with chronic diseases like IBD but also by children with FAP.

PMID- 25950090
TI  - Low efficiency IDO2 enzymes are conserved in lower vertebrates, whereas higher
      efficiency IDO1 enzymes are dispensable.
AB  - Indoleamine 2,3-dioxygenase (IDO) is a Trp-degrading enzyme that catalyzes the
      first step in the kynurenine pathway. Two IDO genes, IDO1 and IDO2, are found in
      vertebrates and the timing of the gene duplication giving rise to the genes has
      been controversial. In the present study, we report that several fishes and two
      turtles also have both IDO1 and IDO2. This represents definitive evidence for the
      gene duplication occurring before the divergence of vertebrates, with IDO1 having
      been lost in a number of lower vertebrate lineages. IDO2 enzymes have a
      relatively low affinity for l-Trp; however, Anolis carolinensis (lizard) IDO2 has
      an affinity for l-Trp comparable to mammalian IDO1 enzymes. We identified a Ser
      residue located in the distal heme pocket of IDO1 (distal-Ser) (corresponding to
      Ser167 of human IDO1) that is conserved in all IDO1 enzymes and the lizard IDO2.
      This residue is conserved as Thr (distal-Thr) in other IDO2 enzymes. Biochemical
      analyses, using IDO variants with either Ser or Thr substitutions, suggest that
      the distal-Ser change was crucial for the improvement in affinity for l-Trp in
      ancient IDO1. The ancestral IDO1 likely had a 'moderate' enzymatic efficiency for
      l-Trp, clearly higher than IDO2 but lower than mammalian IDO1. The distal-Ser of
      lizard IDO2 bestows a high affinity for l-Trp, however, this unique IDO2 has a
      low enzymatic efficiency because of its very low catalytic velocity. Thus, low
      efficiency IDO2 enzymes have been conserved throughout vertebrate evolution,
      whereas higher efficiency IDO1 enzymes are dispensable in many lower vertebrate
      lineages. 

PMID- 25950091
TI  - Clinical features of human metapneumovirus genotypes in children with acute lower
      respiratory tract infection in Changsha, China.
AB  - To explore the epidemiological and clinical features of different human
      metapneumovirus (hMPV) genotypes in hospitalized children. Reverse transcription
      polymerase chain reaction (RT-PCR) or PCR was employed to screen for both hMPV
      and other common respiratory viruses in 2613 nasopharyngeal aspirate specimens
      collected from children with lower respiratory tract infections from September
      2007 to February 2011 (a period of 3.5 years). The demographics and clinical
      presentations of patients infected with different genotypes of hMPV were
      compared. A total of 135 samples were positive for hMPV (positive detection rate:
      5.2%). Co-infection with other viruses was observed in 45.9% (62/135) of cases,
      and human bocavirus was the most common additional respiratory virus. The most
      common symptoms included cough, fever, and wheezing. The M gene was sequenced for
      135 isolates; of these, genotype A was identified in 72.6% (98/135) of patients,
      and genotype B was identified in 27.4% (37/135) of patients. The predominant
      genotype of hMPV changed over the 3.5-year study period from genotype A2b to A2b
      or B1 and then to predominantly B1. Most of clinical features were similar
      between patients infected with different hMPV genotypes. These results suggested
      that hMPV is an important viral pathogen in pediatric patients with acute lower
      respiratory tract infection in Changsha. The hMPV subtypes A2b and B1 were found
      to co-circulate. The different hMPV genotypes exhibit similar clinical
      characteristics.

PMID- 25950093
TI  - Predictive factors for positive or negative pathology in loop and laser
      conizations.
AB  - OBJECTIVE: The main purpose of this study is to predict positive-negative
      pathology in association with operative indications in laser and loop
      conizations. MATERIALS AND METHODS: This retrospective study comprises two groups
      of women, the first group composed of 74 loop conizations, the second of 78 laser
      cones. Positive endocervical curettage, unsatisfactory colposcopy with no visible
      lesion or junction, discrepant cytology and biopsy, suspicion of invasion, or a
      glandular lesion were considered as indications for cones. All cones were
      performed under local intramucous anesthesia, and 15 mm of endocervical mucosa
      was removed. RESULTS: Loop and laser cone outcomes were comparable for age,
      parity, and pathology with negative or positive margins. Endocervical curettage
      of lesions of cervical intraepithelial neoplasia grades 2 and 3 (CIN2 and CIN3)
      predicted both higher cone pathology (p =.048) and high-grade squamous
      intraepithelial lesions, as evidenced by preoperative cytology (p =.000). Among
      32 negative-margins cases, 2 (6.3%) had CIN persistence as compared to 6 patients
      (24%) of 25 positive margins. CONCLUSIONS: Laser and loop cones yield similar
      pathological results, and special care should be used for CIN1 endocervical
      curettage and low-grade squamous intraepithelial lesion cytology with conization
      indication, in regard to the high possibility of negative cone pathology.

PMID- 25950092
TI  - Four patients with a history of acute exacerbations of COPD: implementing the
      CHEST/Canadian Thoracic Society guidelines for preventing exacerbations.
AB  - The American College of Chest Physicians and Canadian Thoracic Society have
      jointly produced evidence-based guidelines for the prevention of exacerbations in
      chronic obstructive pulmonary disease (COPD). This educational article gives four
      perspectives on how these guidelines apply to the practical management of people
      with COPD. A current smoker with frequent exacerbations will benefit from support
      to quit, and from optimisation of his inhaled treatment. For a man with very
      severe COPD and multiple co-morbidities living in a remote community, tele-health
      care may enable provision of multidisciplinary care. A woman who is admitted for
      the third time in a year needs a structured assessment of her care with a view to
      stepping up pharmacological and non-pharmacological treatment as required. The
      overlap between asthma and COPD challenges both diagnostic and management
      strategies for a lady smoker with a history of asthma since childhood. Common
      threads in all these cases are the importance of advising on smoking cessation,
      offering (and encouraging people to attend) pulmonary rehabilitation, and the
      importance of self-management, including an action plan supported by
      multidisciplinary teams. 

PMID- 25950094
TI  - Atypical glandular cells of undetermined significance: the experience at long
      island jewish medical center.
AB  - OBJECTIVES: Our aim was to determine the rate, accuracy and histological
      correlates of cytological smears re-ported as atypical glandular cells of
      undetermined significance (AGUS). MATERIALS AND METHODS: Cervical cytological
      smears reported as AGUS from January 1991 to December 1995 were reviewed and
      correlated with subsequent biopsies and Papanicolaou (Pap) smears. RESULTS: The
      AGUS rate was 0.53% (n = 114 of 21,468). Sixty-nine of the 114 cases (61%) had
      corresponding tissue specimens (biopsies and curettage), and 24 (21%) cases had
      subsequent Pap smears. No follow-up was available in 17 cases (15%). Four AGUS
      diagnoses represented recurrent high-grade squamous intraepithelial lesions.
      These lesions did not have biopsy confirmation but were treated on the basis of
      the Pap smear and colposcopic findings. Twenty-seven (23.6%) cases represented
      premalignant or malignant lesions, with a mean age of 52 years. Those patients
      with endometrial pathology had a mean age of 63 years, and those with squamous
      neoplastic lesions had a mean age of 39 years. Findings included 12 endometrial
      lesions (5 hyperplasias and 7 carcinomas); 2 adenocarcinomas in situ; 11 squamous
      lesions (10 squamous intraepithelial lesions and 1 squamous carcinoma); and 2
      lesions with concomitant glandular and squamous abnormalities. Eleven of the 12
      cases re-ported as AGUS-favor endometrial cells and 7 of the 12 cases reported as
      AGUS-favor neoplastic (AGFN) showed significant pathology. One screening error
      and 10 interpretive errors occurred (6 overcalled, 4 undercalled); however, no
      adverse out-comes were reported. CONCLUSIONS: AGUS-favor endometrial cells
      usually occur in older patients and almost always is associated with premalignant
      or malignant lesions. Endometrial curettage should be performed on these
      patients. AGFN often indicates a significant lesion, usually occurs in younger
      patients, and colposcopically directed biopsy or endocervical curettage should be
      performed. AGUS-favor reactive and AGUS unspecified are less likely to represent
      significant lesions, and a conservative clinical approach (interval Pap smears)
      may be appropriate.

PMID- 25950095
TI  - Atypical glandular cells of undetermined significance and other glandular cell
      abnormalities in a high-risk population.
AB  - OBJECTIVES: We set out to determine our rate of atypical glandular cells of
      undetermined significance (AGUS) classification, to compare our AGUS rate to
      rates reported by others, and to determine the correlation between AGUS and
      histological abnormalities in our population. MATERIALS AND METHODS: Reports from
      all Papanicolaou (Pap) smears and associated histological specimens interpreted
      by the University of Florida Department of Pathology between 1992 and 1996 were
      reviewed. RESULTS: A total of 462 (1.2%) of 39,484 Pap smears were classified as
      epithelial cell abnormality-glandular cell, with 328 (0.83%) AGUS, 102 (0.26%)
      endometrial cells out of phase or in a postmenopausal woman, and 32 (0.08%)
      adenocarcinoma. A total of 146 (45%) of the AGUS cases had timely biopsies: 95
      (65.1%) had benign findings, 27 (18.5%) had cervical intraepithelial neoplasia,
      14 (9.6%) had adenocarcinoma (10 endometrial, 2 endocervical, 2 extrauterine), 9
      (6%) had endometrial hyperplasia, and 1 (0.7%) showed endocervical glandular cell
      dysplasia. CONCLUSIONS: AGUS on Pap is associated with a clinically significant
      histological abnormality in a moderate percentage of patients. Both squamous and
      glandular lesions are seen, supporting the need for aggressive evaluation of the
      cervix, endocervix, and endometrium when AGUS is reported.

PMID- 25950096
TI  - Squamous intraepithelial lesions of the cervix in a high-risk population.
AB  - OBJECTIVES: We set out to examine our use of the squamous intraepithelial lesion
      (SIL) category, compare our SIL rate to rates reported by others, and determine
      the corre-lation between SIL and histologically proven cervical intraepithelial
      neoplasia (CIN) in our population. MATERIALS AND METHODS: Reports from all
      Papanicolaou smears and associated histological specimens interpreted by the
      University of Florida Department of Pathology between 1992 and 1996 were
      reviewed. RESULTS: Of 39,484 Papanicolaou smears, 2,101 (5.3%) were classified as
      low-grade squamous intraepithelial lesion (LGSIL) and 1,366 (3.5%) were
      classified as high-grade (HGSIL). Of the LGSIL cases, 972 (46.3%) underwent
      timely biopsy: Findings were benign in 29.9%; 41.7% had CIN1,20.9% had CIN2, and
      7.5% had CIN3. Of the HGSIL cases, 932 (68.2%) underwent timely biopsy: Findings
      were benign in 12.3%; 17.1% had CIN1, 26.7% had CIN2, 42.2% had CIN3, and 1.6%
      showed squamous cell carcinoma. Condusions. Our LGSIL rate is similar to reported
      rates, but our HGSIL rate of 3.5% is higher. We found good correlation between
      SIL on Papanicolaou smear and CIN on biopsy (70.1% for LGSIL and 86% for HGSIL).

PMID- 25950097
TI  - Conservative management of positive resection margins after loop electrosurgical
      excision procedure.
AB  - OBJECTIVES: We sought to determine the pres-ence of residual neoplasia in women
      reported previously as having positive surgical margins after loop
      electrosurgical excision procedure of the cervix. METHODS: Of 460 loop
      electrosurgical excision procedures of the cervix, 127 (27.6%) had margins
      positive for cervical intraepithelial neoplasia. We re-viewed the charts of 74
      patients (58%). We found positive en-docervical margins in 68 of 74 (92%) and
      positive ectocervical margins in 4 of 74 (5%). In 2 of 74 (3%), the location of
      the positive margin was unknown. Patients were followed either with three
      consecutive Papanicolaou smears (n = 43) during the year after the procedure or
      with conization or hysterec-tomy (n = 31). RESULTS: The overall rate of
      spontaneous regression of cervical intraepithelial neoplasia was 64%. The small
      study sample does not permit us to conclude whether either positive ectocervical
      or endocervical margins were more amenable to recurrence. No invasive cancer was
      diagnosed in the study. CONCLUSIONS: With a reliable patient population, patients
      with cervical margins positive for cervical intraepithelial neoplasia after loop
      electrosurgical excision procedure can be followed safely with cytology.

PMID- 25950098
TI  - Predicting risk factors for suboptimal excision in women undergoing cold-knife
      cone biopsy.
AB  - OBJECTIVE: Our goal was to identify risk factors for suboptimal excision in
      relation to a positive endocervical curettage (ECC) after conization or positive
      specimen margin. MATERIALS AND METHODS: A retrospective review of referral cy
      tology and colposcopy results for 280 women undergoing conization at two urban
      teaching centers was performed. Mann-Whitney or Pearson's chi-square test was
      used to de-termine significant associations between preoperative variables and
      positive cone margin, positive intraoperative ECC, and either positive margin or
      positive intraoperative ECC. RESULTS: Cytology grade, gravidity, parity, and race
      were not significantly correlated with any outcome variable. Using lo-gistical
      regression analyses, correlates of positive ECC after conization included
      increasing age (p = .01), positive colpo-scopic biopsy (p = .01), colposcopic
      inadequacy (p = .01), and positive preoperative ECC (p = .03). Positive
      preoperative ECC was the only significant risk factor for positive cone margin (p
      = .02) or the combination of either positive intraoperative ECC or positive cone
      margin (p = .0001). Condusion. A positive preoperative ECC is the best predictor
      of suboptimal excision at conization and should be performed unless contraindi
      cated.

PMID- 25950099
TI  - Dimethylether treatment for condyloma acuminata in women.
AB  - OBJECTIVE: Our aim was to test a new cryosurgical wart treatment, dimethylether
      (Histofreezer), for clinical effi-cacy in newly diagnosed cases of genital warts.
      METHODS: All patients of the gynecology clinic of a teaching hospital who were at
      least 12 years of age and who had between one and eight external genital warts
      were eligible. Treatment occurred at the initial visit and at follow-up visits at
      2, 4, 6, and 8 weeks. If all warts were gone at any particular visit, the patient
      had completed the study and was not required to return. RESULTS: In 14 of 15
      patients [93%; 95% confidence interval (Cl), 81-100%], all warts resolved within
      the 8-week study period. This included 39 of 44 warts (89%; 95% Cl 80-98%). Most
      warts [35 of 44 (80%)] resolved within 4 weeks. One patient with five warts
      failed treatment. No known complications were seen. Condusion. Dimethylether
      (Histofreezer) is an effective cryosurgical treatment for genital warts.

PMID- 25950100
TI  - The absence of human papillomavirus in amniotic fluid.
AB  - OBJECTIVES: The objective of this multicenter trial was to determine the
      incidence of human papillomavirus (HPV) in the amniotic fluid of pregnant
      patients. METHODS: Fifty-three pregnant patients undergoing genetic counseling or
      amniocentesis for preterm labor were entered into the study. Cervical swabs and
      amniotic fluid samples were ob-tained at the time of entry. Demographical
      questionnaires were completed by all patients. All samples underwent HPV analysis
      using polymerase chain reaction. RESULTS: The incidence of cervical HPV and
      cervical intraepithelial neoplasia in this population was 24% and 4%,
      respectively. The analysis of 49 amniotic fluid samples revealed the absence of
      HPV in each specimen. CONCLUSIONS: The absence of HPV in the amniotic fluid of
      patients with cervical colonization does not support a mechanism of prenatal
      transmission in the general population.

PMID- 25950101
TI  - The efficacy of two papanicolaou devices: a randomized study in a high-risk
      population.
AB  - OBJECTIVES: Our goal was to determine the abil-ity of two Papanicolaou (Pap)
      smear devices to identify cor-rectly cervical intraepithelial neoplasia (CIN) in
      a high-risk population. METHODS: Two hundred and seven nonpregnant women,
      referred to the colposcopy clinics at two University of Tennessee Family Practice
      Centers in Memphis and Jackson, were enrolled in the study if the referral Pap
      smear contained atypical cells of undetermined significance, a low-grade cervical
      intraepithelial lesion, or a high-grade intraepithelial le-sion. After they were
      randomly assigned to Pap smear with ei-ther the modified Ayre spatula and
      Cytobrush or the Acellon Combi brush, colposcopy and appropriate biopsies were
      per-formed in these women. Pap cytology and pathology results were compared using
      descriptive statistics and chi-square or Fischer's exact test. RESULTS:
      Satisfactory Pap smears were ob-tained in 91 % of the Combi brush specimens and
      100% of the Ayre spatula-Cytobrush specimens. Biopsies revealed that 85% of
      patients had CIN. Twenty-six percent of patients had CIN2 or CIN3. The
      sensitivities, specificities, and false-negative rates for the identification of
      any CIN were 69, 73, and 31% for the Ayre spatula-Cytobrush combination, and 72,
      81, and 28% for the Combi brush, respectively. CONCLUSIONS: The Ac-cellon Combi
      brush identified cervical disease as well as the spatula-Cytobrush combination in
      this high-risk population. The ability of a device to obtain endocervical cells
      did not cor-relate with its efficacy in identifying CIN.

PMID- 25950102
TI  - Why, How, and When the Cytological Diagnosis of ASCUS Should Be Eliminated.

PMID- 25950103
TI  - Home study course: summer 1998.
AB  - OBJECTIVE: The Home Study Course is intended for the prac-ticing colposcopist or
      practitioner who is seeking to develop or enhance his or her colposcopic skills.
      The goal of the course is to present colposcopic cases that are unusual or
      instructive in terms of appearance, presentation, or management or that
      demonstrate new and important knowledge in the area of colposcopy or pathology.
      Participants may benefit from read-ing and studying the material or from testing
      their knowledge by answering the questions.ACCME AccreditationThe American
      Society for Colposcopy and Cervical Pathology (ASCCP) is accredited by the
      Accreditation Council for Continuing Medical Education (ACCME) to sponsor
      continuing medical education for physicians. The ASCCP designates this continuing
      medical education activity for 1 credit hour in Category I of the Physicians'
      Recognition Award of the American Medical Association. Credit is available for
      those who choose to apply. The Home Study Course is planned and produced in
      accordance with the ACCME's Essentials.

PMID- 25950104
TI  - The american society for colposcopy and cervical pathology.

PMID- 25950105
TI  - Chronic pelvic pain in women: the need for multidisciplinary evaluation and
      treatment.

PMID- 25950106
TI  - A papanicolaou smear with psammona bodies.

PMID- 25950107
TI  - Is LEEP the Cesarean Delivery of Cervical Intraepithelial Neoplasia?

PMID- 25950108
TI  - Kinetics of the addition of olefins to Si-centered radicals: the critical role of
      dispersion interactions revealed by theory and experiment.
AB  - Solution-phase rate constants for the addition of selected olefins to the
      triethylsilyl and tris(trimethylsilyl)silyl radicals are measured using laser
      flash photolysis and competition kinetics. The results are compared with
      predictions from density functional theory (DFT) calculations, both with and
      without dispersion corrections obtained from the exchange-hole dipole moment
      (XDM) model. Without a dispersion correction, the rate constants are consistently
      underestimated; the errors increase with system size, up to 10(6) s(-1) for the
      largest system considered. Dispersion interactions preferentially stabilize the
      transition states relative to the separated reactants and bring the DFT
      calculated rate constants into excellent agreement with experiment. Thus,
      dispersion interactions are found to play a key role in determining the kinetics
      for addition reactions, particularly those involving sterically bulky functional
      groups. 

PMID- 25950109
TI  - Effects of a Presidential Candidate's Comments on HPV Vaccine.
AB  - During and after the 2011 Republican presidential debate, a candidate questioned
      the safety of HPV vaccine. The authors aimed to determine the effect of these
      comments on parents. A national sample of 327 parents with adolescent sons ages
      11-17 years completed online surveys in fall 2010 (baseline, about 1 year before
      the debate) and 2011 (follow-up, about 1 month after the debate). The authors
      used regression models to examine the association of parents' awareness of the
      candidate's comments with HPV vaccine initiation among their sons, their
      willingness to get sons free HPV vaccine, and their beliefs about potential harms
      of HPV vaccine. Overall, 17% of parents reported hearing about the Republican
      presidential candidate's comments about HPV vaccine. Parents aware of the
      comments had a larger increase between baseline and follow-up in the belief that
      HPV vaccine might cause short-term health problems compared with parents who were
      not aware. Although the candidate's comments may have increased some parents'
      beliefs about the short-term harms of HPV vaccine, the comments had no effect on
      other beliefs, willingness to vaccinate, or behavior. Having accurate information
      about HPV vaccine that is readily available to the public during such
      controversies may diminish their effect. 

PMID- 25950110
TI  - An ionically tagged water-soluble artificial enzyme promotes the
      dephosphorylation reaction with nitroimidazole: enhanced ionic liquid effect and
      mechanism.
AB  - In this paper, we describe a novel synthesized ionically tagged water-soluble
      artificial enzyme (PI) that can efficiently cleave phosphate esters, with
      enhanced an ionic liquid effect through cooperative effects for the substrate
      activation and further nucleophilic reaction. The dephosphorylation reaction with
      PI was evaluated in the presence and absence of 2-methyl-4(5)-nitroimidazole,
      showing impressive rate enhancements of up to 2 * 10(6)-fold, ascribed to the
      imidazolide species known as excellent nucleophiles, and formed favorably at
      lower pH values in the presence of PI. 

PMID- 25950111
TI  - The Modern Clinical Neuroimager: Leading the Next Generation in Stroke.
AB  - The recent culmination of imaging-endowed endovascular stroke trials has
      decisively proven the utility of clinically relevant neuroimaging in improving
      the outcome of patients with potentially debilitating neurological disorders.
      These large multicenter trials conducted across several continents notably
      utilized a variety of multimodal CT/MRI modalities to rapidly identify a
      favorable collateral profile that presages clinically beneficial
      revascularization. The modern clinical neuroimager may accelerate complex
      decision-making through the rational use of a variety of imaging modalities and
      an active feedback loop of imaging at the bedside. The modern clinical
      neuroimager is often the initial care provider for a wide range or type of stroke
      patients from hemorrhage to ischemia, armed with the incredibly important aspects
      of clinical history and examination findings and best poised to utilize imaging
      to guide therapy from acute stroke to recovery and prevention. The next
      generation in stroke should not exclusively focus on whether to order a CT or MRI
      counting minutes at the bedside, but actively and efficiently integrate the vast
      wealth of information available when imaging is used in the proper clinical
      context. The novel endovascular era in stroke provides an ideal venue for the
      synergistic goals of translating research advances, improving patient outcomes
      and ongoing education as a modern neuroimager. 

PMID- 25950112
TI  - Diastereoselective and enantioselective silylation of 2-arylcyclohexanols.
AB  - The silylation-based kinetic resolution of trans 2-arylcyclohexanols was
      accomplished by employing a triaryl silyl chloride as the derivatizing reagent
      with a commercially available isothiourea catalyst. The methodology is selective
      for the trans diastereomer over the cis, which provides an opportunity to
      selectively derivatize one stereoisomer out of a mixture of four. By employing
      this technology, a facile, convenient method to form a highly enantiomerically
      enriched silylated alcohol was accomplished through a one-pot reduction
      silylation sequence that started with a 2-aryl-substituted ketone. 

PMID- 25950113
TI  - Infantile Hemangioma: Clinical Characteristics and Efficacy of Treatment with the
      Long-Pulsed 1,064-nm Neodymium-Doped Yttrium Aluminum Garnet Laser in 794 Chinese
      Patients.
AB  - OBJECTIVE: This study aimed to evaluate the clinical characteristics of infantile
      hemangiomas (IHs) and the safety and efficacy of the long-pulse 1,064-nm
      neodymium-doped yttrium aluminum garnet (Nd:YAG) laser for definitive treatment
      of IHs in 794 Chinese patients. METHODS: Infants with hemangiomas who had
      received long-pulse 1,064-nm Nd:YAG laser treatment in our department in the last
      5 years were recruited. Demographic and clinical characteristics were recorded
      and outcomes of long-pulse 1,064-nm Nd:YAG laser treatment were assessed.
      Statistical analyses were performed to identify factors that affected the
      efficacy of treatment. RESULTS: The efficacy of long-pulse 1,064-nm Nd:YAG laser
      for the treatment of IHs in all patients in our study was 87.57%. Efficacy did
      not depend on sex or the location of the lesion. Older age and superficial
      hemangioma were the primary factors contributing to greater efficacy of long
      pulse 1,064-nm Nd:YAG laser treatment for IHs. The most common side effects were
      pigment changes, skin atrophy, and wrinkled redundant skin, which usually
      resolved spontaneously within 1 to 3 years. CONCLUSIONS: Long-pulse 1,064-nm
      Nd:YAG laser is a safe and efficacious treatment for IHs.

PMID- 25950114
TI  - Power relations and contrasting conceptions of evidence in patient-involvement
      processes used to inform health funding decisions in Australia.
AB  - We collected and analysed views of key stakeholders on the processes used to
      involve patient organisations in health care funding decision making in
      Australia. We conducted 12 semi-structured interviews with patient organisation
      representatives and members of Advisory Committees that provide advice to the
      Australian Department of Health and employ Health Technology Assessment (HTA) as
      an evaluation framework. Using two theoretical frameworks, we analysed structural
      and contextual elements pertaining to the involvement processes. The findings
      reported in this article relate to interviewees' perspectives on contextual
      elements, analysed using a Foucauldian lens. These elements include: the
      perspectives of marginalised voices; the diversity of views on what ought to be
      considered valid evidence in a HTA setting; and the relationships between
      stakeholders, along with how these relationships impact on involvement processes
      and the outcomes of those processes. The findings demonstrate that the
      involvement processes currently used are deemed inadequate by both patient
      organisation representatives and Advisory Committee members, but for different
      reasons connected to how different stakeholders conceptualise evidence. Advisory
      Committee members viewed evidence as encompassing clinical outcomes and patient
      preferences, whereas patient organisation representatives tended to view evidence
      as encompassing aspects not directly related to a disease entity, such as the
      social and emotional aspects of patients' experiences in living with illness.
      Patient organisation representatives reported interacting with other stakeholders
      (especially industry) to increase the influence of their conception of evidence
      on decision making. The use of this strategy by interviewees illustrates how
      power struggles occur in government decision-making processes which involve both
      medical expertise and patients' accounts. Such struggles, and the power
      differentials they reflect, need to be considered by those responsible for
      designing and implementing meaningful public- and patient-involvement processes. 

PMID- 25950115
TI  - Circulating microRNAs as novel prognosis biomarkers for head and neck squamous
      cell carcinoma.
AB  - Circulating microRNAs (miRNAs) are emerging as promising non-invasive biomarkers
      for human cancer. Head and neck squamous cell carcinoma (HNSCC) is a prevalent
      malignancy worldwide, but its overall survival has remained unchanged in the past
      3 decades. Biomarkers for evaluating efficacy of cancer therapy are urgently
      needed. To explore circulating miRNAs as cancer therapy biomarkers, we initially
      identified that 8 miRNAs were distinctly dysregulated in cancerous tissues
      compared with adjacent non-cancerous counterparts from 16 patients, using
      microarray and real-time PCR. Based on this discovery, the comparison study was
      performed between pre- and 6 months post-operative paired plasma samples on 9
      patients. MiR-99a, which was down-regulated in cancerous tissues, was
      significantly increased in plasma after operation. Meanwhile, oncomiR miR-21 and
      miR-223 that were up-regulated in cancerous tissues, were significantly reduced
      in post-operative plasma samples. We firstly report the significant changes of
      miR-99a in plasma of HNSCC patients after surgery. Furthermore, plasma miR-223
      was inversely increased in a patient whose cancer relapsed within 6 months after
      operation. We conclude that these circulating miRNAs may serve as biomarkers to
      evaluate the efficacy of therapy and the prognosis of HNSCC. 

PMID- 25950116
TI  - Contemplating the Diagnostic Certainty of Primary Iris Mucosa-Associated Lymphoid
      Tissue Lymphoma.

PMID- 25950117
TI  - Effect of final irrigation protocols on push-out bond strength of an epoxy resin
      root canal sealer to dentin.
AB  - The purpose of the present study was to evaluate the effect of different final
      irrigation protocols on push-out bond strength of an epoxy resin root canal
      sealer to dentin. Eighty single-rooted anterior teeth were used. The root canals
      were partially prepared using a rotary system and the final diameter was
      standardised using a #5 Gates-Glidden drill prior to the push-out bond test.
      During chemomechanical preparation, 5.25% NaOCl or 2% CHX gel was used. For smear
      layer removal, 17% ethylenediaminetetraacetic acid (EDTA) or QMix 2 in 1 was
      applied for 3 min. As final irrigant, 1 mL of NaOCl, CHX solution or distilled
      water was used. On conclusion of preparation, canals were filled with gutta
      percha/AH Plus sealer. Bond strength was measured by the push-out test. Data were
      statistically analysed by Kruskal-Wallis and Mann-Whitney U-tests. The group
      NaOCl/EDTA/NaOCl showed significantly higher bond strength values than other
      groups. In all groups, there were mainly mixed failure patterns. It can be
      concluded that 5.25% NaOCl proved to be the best solution for the final
      irrigation when combined with EDTA. The final irrigation protocols affect the
      push-out bond strength of AH Plus to dentin. 

PMID- 25950118
TI  - Study on interactions between suspended matter and biofouling formed by treated
      sewage.
AB  - Heat exchangers used for treated sewage energy recovery usually suffer from the
      composite fouling problem, which seriously impairs the heat transfer efficiency.
      Treated sewage heat exchanger composite fouling is mostly composed of biofouling
      and is notably affected by interactions between the biofouling and suspended
      matter. Experiments were performed using simulated treated sewage and two kinds
      of simulated suspended matter, silicon dioxide particles and polyamide filaments,
      to model the interactions. Different flow velocities, particle sizes and
      concentrations were tested with their influences presented by the fouling wet
      weight changes. Empirical equation and threshold were developed based on the
      results to predict whether the suspended matter promotes or impedes fouling
      growth. The results indicate that proper control of the flow velocities, particle
      sizes and concentrations of suspended matter using empirical equation and
      threshold can inhibit fouling by reducing unwanted positive interactions and
      promoting beneficial negative interactions. The filament interactions were
      analysed and the unique attachment mechanisms of filaments were discussed for the
      first time. 

PMID- 25950119
TI  - The first example of a one-step synthesis of 2'-O-acetyl aryl-D-glucopyranosides.
AB  - A selective acidic system for partial deacetylation of phenolic d
      glucopyranosides per-acetates has been developed that allows synthesis of the
      corresponding 2'-O-acetyl-D-glucosides. Many disadvantages of generally used
      methods for preparing such mono-acyl derivatives involving multistep procedures
      or the use of enzymes are avoided. The ion at m/z 289 in mass spectra of their
      TMS derivatives indicates a particular and characteristic fragmentation pattern
      of these 2'-O-acetyl derivatives of d-glucopyranosides. Quantum-chemical
      calculations applying B3LYP/TZVP level of theory revealed the stability of 2'-O
      acetyl glucopyranoside if compare with 3'-, 4'- and 6'- O-acetyl glucopyanosides.

PMID- 25950120
TI  - A multivariate approach for high throughput pectin profiling by combining glycan
      microarrays with monoclonal antibodies.
AB  - Pectin-one of the most complex biomacromolecules in nature has been extensively
      studied using various techniques. This has been done so in an attempt to
      understand the chemical composition and conformation of pectin, whilst
      discovering and optimising new industrial applications of the polymer. For the
      last decade the emergence of glycan microarray technology has led to a growing
      capacity of acquiring simultaneous measurements related to various carbohydrate
      characteristics while generating large collections of data. Here we used a
      multivariate analysis approach in order to analyse a set of 359 pectin samples
      probed with 14 different monoclonal antibodies (mAbs). Principal component
      analysis (PCA) and partial least squares (PLS) regression were utilised to obtain
      the most optimal qualitative and quantitative information from the spotted
      microarrays. The potential use of microarray technology combined with
      chemometrics for the accurate determination of degree of methyl-esterification
      (DM) and degree of blockiness (DB) was assessed. 

PMID- 25950121
TI  - Synthesis of pyrrolidine-based analogues of 2-acetamidosugars as N-acetyl-D
      glucosaminidase inhibitors.
AB  - A ring-contraction strategy applied to beta-azido,gamma-hydroxyazepanes yielded
      after functional group manipulation new tetrahydroxylated pyrrolidines displaying
      an acetamido moiety, one of these iminosugars demonstrating low micromolar
      inhibition on N-acetylglucosaminidases. 

PMID- 25950122
TI  - The spinning apparatus of webspinners--functional-morphology, morphometrics and
      spinning behaviour.
AB  - Webspinners (Insecta: Embioptera) have a distinctly unique behaviour with related
      morphological characteristics. Producing silk with the basitarsomeres of their
      forelegs plays a crucial role in the lives of these insects--providing shelter
      and protection. The correlation between body size, morphology and morphometrics
      of the spinning apparatus and the spinning behaviour of Embioptera was
      investigated for seven species using state-of-the-art methodology for behavioural
      as well as for morphological approaches. Independent contrast analysis revealed
      correlations between morphometric characters and body size. Larger webspinners in
      this study have glands with greater reservoir volume, but in proportionally
      smaller tarsi relative to body size than in the smaller species. Furthermore, we
      present a detailed description and review of the spinning apparatus in Embioptera
      in comparison to other arthropods and substantiate the possible homology of the
      embiopteran silk glands to class III dermal silk glands of insects.

PMID- 25950123
TI  - Can the dopaminergic-related effects of general anesthetics be linked to
      mechanisms involved in drug abuse and addiction?
AB  - BACKGROUND: General anesthetics (GA) are well known for the ability to induce a
      state of reversible loss of consciousness and unresponsiveness to painful
      stimuli. However, evidence from animal models and clinical studies show that GA
      exposure may induce behavioral changes beyond acute effects. Most research and
      concerns are focused on changes in cognition and memory. METHODS: We will look at
      effects of GA on behavior that is mediated by the dopaminergic system. RESULTS:
      Pharmacological resemblance of GA with drugs of abuse, and the complexity and
      importance of dopaminergic systems in both reward seeking and addictive illnesses
      make us believe that it deserves an overview about what is already known and what
      matters to us as healthcare workers and specifically as anesthesiologists.
      CONCLUSION: A review of available evidence strongly suggests that there may be a
      link between the effects of GA on the brain and substance abuse, partly explained
      by their influence on the dopaminergic system.

PMID- 25950125
TI  - Is Routine Curettage a Useful Tool to Evaluate Persistent Tumor in Patients Who
      Underwent Primary Chemoradiation for Locally Advanced and/or Lymph Node Positive
      Cervical Cancer?
AB  - OBJECTIVE: Response evaluation after primary chemoradiation (RCTX) in patients
      with cervical cancer remains difficult. Routine hysterectomy after primary RCTX
      is associated with considerable surgical morbidity without impact on survival.
      The purpose of the present study was to evaluate value of routine curettage after
      RCTX to detect persistent tumor. METHODS: Between 2006 and 2012, patients (n =
      217) with cervical cancer in International Federation of Gynecology and
      Obstetrics stages IB1 N1 (14%), IB2 (9%), IIA (5%), IIB (46%), IIIA (4%), IIIB
      (15%), IVA (6%), and IVB (1%), respectively, underwent primary RCTX. After RCTX,
      curettage was recommended to all patients to evaluate response. RESULTS: In 136
      (63%) of patients with cervical cancer, 1 or 2 consecutive curettages were
      performed at least 6 weeks after primary RCTX without any complications. In 21
      (15%) patients, at least 1 curettage was positive for cervical cancer. In 7
      patients, secondary hysterectomy was performed after 1 positive finding and
      persistent tumor was found in all of them. In the remaining 14 patients, there
      were 2 positive curettages in 5, 1 undetermined result followed by 1 positive in
      3, and 1 positive followed by 1 negative in 6 patients, respectively. In the
      latter group, no tumor was detected in the uterus, whereas in all other patients
      with 2 curettages except one, residual carcinoma was detected. Five (24%) of 21
      patients with positive histology are free of disease during follow-up. Decision
      for or against secondary hysterectomy was correct due to histological finding of
      curettage in 99%. CONCLUSIONS: Routine curettage is a useful tool to guide
      decision for secondary hysterectomy with high accuracy after primary RCTX and
      avoids overtreatment.

PMID- 25950124
TI  - Intraoperative fluorescence imaging to localize tumors and sentinel lymph nodes
      in rectal cancer.
AB  - Tumor involvement at the resection margin remains the most important predictor
      for local recurrence in patients with rectal cancer. A careful description of
      tumor localization is therefore essential. Currently, endoscopic tattooing with
      ink is customary, but visibility during laparoscopic resections is limited. Near
      infrared (NIR) fluorescence imaging using indocyanine green (ICG) could be an
      improvement. In addition to localize tumors, ICG can also be used to identify
      sentinel lymph nodes (SLNs). The feasibility of this new technique was explored
      in five patients undergoing laparoscopic low anterior resection for rectal
      cancer. Intraoperative tumor visualization was possible in four out of five
      patients. Fluorescence signal could be detected 32 +/- 18 minutes after incision,
      while ink could be detected 42 +/- 21 minutes after incision (p = 0.53). No
      recurrence was diagnosed within three months after surgery. Ex vivo imaging
      identified a mean of 4.2 +/- 2.7 fluorescent lymph nodes, which were appointed
      SLNs. One out of a total of 83 resected lymph nodes contained a micrometastasis.
      This node was not fluorescent. This technical note describes the feasibility of
      endoscopic tattooing of rectal cancer using ICG:nanocolloid and NIR fluorescence
      imaging during laparoscopic resection. Simultaneous SLN mapping was also
      feasible, but may be less reliable due to neoadjuvant therapy.

PMID- 25950126
TI  - Fertility-Sparing Treatment of Early Endometrial Cancer and Complex Atypical
      Hyperplasia in Young Women of Childbearing Potential.
AB  - OBJECTIVE: To evaluate oncologic and reproductive outcome with levonorgestrel
      releasing intrauterine system combined with gonadotropin-releasing hormone
      agonist in women with grade 1 endometrial carcinoma, and the levonorgestrel
      monotherapy in women with complex atypical hyperplasia. MATERIALS/METHODS: A
      prospective study was conducted. We analyzed the clinical characteristics of 70
      patients younger than 42 years (mean age, 33 years) with a diagnosis of complex
      atypical endometrial hyperplasia (AEH) or grade 1 endometrial adenocarcinoma who
      were treated with hormonal therapy at the Division of Gynecologic Oncology of
      P.A. Hertsen Moscow Cancer Research Institute from February 2009 to December
      2012. Patients with complex AEH received monotherapy with levonorgestrel
      releasing intrauterine system (Mirena, Shering, Finland; 52 mg). Patients with a
      diagnosis of grade 1 endometrial cancer were treated with levonorgestrel
      releasing intrauterine system combined with gonadotropin-releasing hormone
      agonist (Zoladex; AstraZeneca UK Limited, UK; 3.6-mg depot). All the patients
      received hormonal therapy for a minimum of 6 months. Pretreatment evaluation
      consisted of transabdominal and transvaginal ultrasound in grayscale, color
      Doppler ultrasound, contrast-enhanced magnetic resonance imaging, cervical
      hysteroscopy, Pipelle endometrial biopsy, and morphological and
      immunohistochemical characteristics of the tissue. RESULTS: Seventy patients were
      included in study analyses. Twenty three (72%) of 32 patients with adenocarcinoma
      and 35 (92%) of 38 patients with AEH had complete remission, defined as the
      absence of any carcinoma or hyperplasia on endometrial sampling specimens. Among
      these cases, 2 patients with adenocarcinoma and 1 patient with AEH had recurrence
      after their complete response. Nine patients had persistent disease. Eight
      patients had 10 conceptions, resulting in 8 live births. CONCLUSIONS: The
      suggested conservative treatment strategy can be considered as a valid
      therapeutic option for young women of childbearing potential with atypical
      endometrial hyperplasia and grade 1 endometrial adenocarcinoma who wish to
      preserve their fertility and thus may be recommended as an alternative to
      hysterectomy. Close follow-up during and after the treatment period is strictly
      required.

PMID- 25950128
TI  - Unique human papillomavirus-type distribution in South African women with
      invasive cervical cancer and the effect of human immunodeficiency virus
      infection.
AB  - OBJECTIVES: Cervical cancer is the most common cause of cancer-related deaths
      among South African women. Viral types associated with cervical cancer may differ
      not only between countries and regions, but possibly also between human
      immunodeficiency virus (HIV)-infected and noninfected women. METHODS: In a
      population with high HIV prevalence, human papillomavirus (HPV)-type infections
      detected with DNA analyses were reported in a cohort of 299 women diagnosed with
      invasive cervical cancer. RESULTS: One hundred fifty-four women tested HIV
      negative, 77 tested HIV positive, and HIV status was unknown for 68 women. The
      mean age for HIV-positive women was 41.3 years, and that for HIV-negative women
      was 55.8 years (P < 0.001). Ninety-two percent of women tested HPV-DNA positive.
      Human papillomavirus types 16 and/or 18 were present in 62% of HIV-negative women
      and 65% of HIV-positive women. The 5 most common HPV types in HIV-positive women
      were, in decreasing frequency, HPV 16, 18, 45, 33, and 58. In HIV-negative women,
      the most common HPV types were HPV 16, 18, 35, and 45, followed by HPV 33 and 52.
      Human papillomavirus type 45 was more likely in the HIV positive compared with
      the HIV negative (odds ratio, 3.07; 95% confidence interval, 1.07-8.77). The HIV
      positive women had more multiple high-risk HPV-type infections than did the HIV
      negative women (27% vs 8%, P = 0.001). CONCLUSIONS: A high number of women in
      South Africa with cervical cancer are HIV positive. Without viral cross
      protection, HPV vaccines should prevent around 65% of cervical cancers in this
      population. Human papillomavirus type 45 infection is significantly linked to HIV
      and important for future vaccine developments.

PMID- 25950127
TI  - Does a standardized preoperative algorithm of clinical data improve outcomes in
      patients with ovarian cancer? A quality improvement project.
AB  - OBJECTIVE: To evaluate the potential impact of a standardized preoperative
      algorithm on outcomes of patients with suspected ovarian cancer. METHODS: From
      January 1 to December 31, 2013, patients with suspected ovarian cancer were
      triaged to primary debulking surgery or neoadjuvant chemotherapy/interval
      debulking surgery (NACT/IDS) based on a comprehensive review of preoperative
      clinical data as part of a quality improvement project. Demographics, surgical,
      and postoperative data were collected. RESULTS: A total of 110 patients with
      newly diagnosed ovarian cancer were identified: 68 (62%) underwent PDS with an
      85% optimal debulking rate. The 30-day readmission rate was 14.7% with a 2.9% 60
      day mortality rate. Forty-two patients (38%) underwent NACT. Two patients (4.8%)
      died before receiving NACT. Thirty-five patients have undergone IDS with an 89%
      optimal debulking rate. The 30-day readmission rate was 8.5% with a 5.7% 60-day
      mortality rate after IDS. CONCLUSIONS: Although it is difficult to predict which
      patients will undergo optimal debulking at the time of PDS, surgical morbidity
      and mortality can be decreased by using NACT in select patients. The initiation
      of a quality improvement project has contributed to an improvement in patient
      outcomes at our institution.

PMID- 25950129
TI  - Direct Comparison of Logistic Regression and Recursive Partitioning to Predict
      Lymph Node Metastasis in Endometrial Cancer.
AB  - OBJECTIVE: The purpose was to compare logistic regression model (LRM) and
      recursive partitioning (RP) to predict lymph node metastasis in early-stage
      endometrial cancer. METHODS/MATERIALS: Three models (1 LRM and 2 RP, a simple and
      a complex) were built in a same training set extracted from the Surveillance,
      Epidemiology, and End Results database for 18,294 patients who underwent
      hysterectomy and lymphadenectomy for stage I or II endometrial cancer. The 3
      models were validated in a same validation set of 499 patients. Model performance
      was quantified with respect to discrimination (evaluated by the areas under the
      receiver operating characteristics curves) and calibration. RESULTS: In the
      training set, the areas under the receiver operating characteristics curves were
      similar for LRM (0.80 [95% confidence interval [CI], 0.79-0.81]) and the complex
      RP model (0.79 [95% CI, 0.78-0.80]) and higher when compared with the simple RP
      model (0.75 [95% CI, 0.74-0.76]). In the validation set, LRM (0.77 [95% CI, 0.75
      0.79]) outperformed the simple RP model (0.72 [95% CI, 0.70-0.74]). The complex
      RP model had good discriminative performances (0.75 [95% CI, 0.73-0.77]).
      Logistic regression model also outperformed the simple RP model in terms of
      calibration. CONCLUSIONS: In these real data sets, LRM outperformed the simple RP
      model to predict lymph node metastasis in early-stage endometrial cancer. It is
      therefore more suitable for clinical use considering the complexity of an RP
      complex model with similar performances.

PMID- 25950130
TI  - Analysis of the Association of Matrix Metalloproteinase-1 Gene Promoter
      (rs1799750) Polymorphism and Risk of Ovarian Cancer.
AB  - OBJECTIVE: Studies investigating the association between matrix metalloproteinase
      1 (MMP1) gene promoter 1607-base pair (bp) polymorphism and ovarian cancer risk
      have yielded conflicting results. METHODS: We therefore carried out a meta
      analysis of 754 ovarian cancer cases and 1184 controls from 5 published case
      control studies. The strength of the association between MMP1 1607-bp
      polymorphism and ovarian cancer susceptibility was calculated using pooled odds
      ratios (ORs) with corresponding 95% confidence intervals (CIs). RESULTS: The
      results suggest that no statistically significant associations exist between MMP1
      1607-bp polymorphisms and ovarian cancer risk in all 4 genetic models (2G2G vs
      1G1G: OR, 1.08; 95% CI, 0.81-1.43; P = 0.23; 1G2G vs 1G1G: OR, 1.06; 95% CI, 0.82
      1.36; P = 0.15; 1G2G + 2G2G vs 1G1G: OR, 1.05; 95% CI, 0.83-1.34; P = 0.16; 2G2G
      vs 1G1G + 1G2G: OR, 0.98; 95% CI, 0.80-1.20; P = 0.84). CONCLUSIONS: In summary,
      this meta-analysis showed that the MMP1 1607-bp polymorphism is not associated
      with ovarian cancer risk.

PMID- 25950131
TI  - Preoperative MRI and intraoperative frozen section diagnosis of myometrial
      invasion in patients with endometrial cancer.
AB  - OBJECTIVE: The rate of lymph node metastasis is extremely low in patients with
      low-risk endometrial cancer; lymphadenectomy may be unnecessary for these
      patients under an accurate preoperative diagnosis. The aim of this study was to
      evaluate the diagnostic accuracy of myometrial invasion (MI) on preoperative
      magnetic resonance imaging (MRI) and intraoperative frozen sections (FSs).
      MATERIALS AND METHODS: Endometrial cancer was diagnosed in a total of 378
      patients by preoperative endometrial curettage, preoperative magnetic resonance
      imaging MRI, and intraoperative FSs; the 378 patients underwent hysterectomy. The
      depth of MI was evaluated between the preoperative MRI, intraoperative FSs, and
      final paraffin sections (PSs). The histologic grade was also evaluated between
      preoperative endometrial curettage, intraoperative FSs, and final PSs. RESULTS:
      The sensitivity, specificity, positive predictive value, and negative predictive
      value for deep MI (>= 50%) on MRI were 57.8%, 92.0%, 69.3%, and 87.5%,
      respectively, with a kappa value of 0.53. These figures on FSs were 66.7%, 97.9%,
      90.9%, and 90.4%, with a kappa value of 0.71. When grade 3 endometrioid
      adenocarcinoma, serous carcinoma, clear cell carcinoma, and carcinosarcoma were
      considered high-grade tumors, the grade evaluation at the time of FSs was 70.2%,
      99.0%, 96.1%, and 89.7%, with a kappa value of 0.75. In the patients with low
      grade tumors, including grade 1 or 2 endometrioid adenocarcinoma on preoperative
      endometrial curettage, the rate of unexpected lymph node metastasis did not
      differ significantly between the patients who had a diagnosis of MI and lymph
      node metastasis by MRI and those with diagnosis of MI and histological grade by
      FSs (4.0% vs 2.6%; P > 0.05). CONCLUSIONS: Frozen sections had a higher agreement
      rate for MI than MRI; however, MRI is still considered an acceptable modality to
      guide preoperative decisions regarding lymphadenectomy especially in grade 1 or 2
      endometrioid adenocarcinoma.

PMID- 25950132
TI  - Economic Considerations on the Follow-Up Practice in Gynecologic Cancers: Few
      Lights and Many Shadows From a Literature Review.
AB  - OBJECTIVE: The aim of this review was to analyze the existing literature on the
      cost of follow-up in gynecology oncology. METHODS/MATERIALS: We performed a
      literature search in Medline and NHS CRD (University of Oxford) databases.
      Research strings were mainly based on MESH terms referring to economic studies
      and to neoplasms follow-up/aftercare and cancer recurrences. Two independent
      searches were performed for ovarian neoplasm and uterine neoplasm. Some studies
      were also identified among the references of the selected articles. Potentially
      relevant studies were identified based on the title and abstract by 2 independent
      readers. RESULTS: Finally, the reviewing process selected 2 studies on
      gynecologic cancers in general, including uterine and ovarian cancers, 3 specific
      on ovarian cancer, 7 on endometrium, and 9 on cervix. The identified economic
      literature on economic evaluation of gynecologic cancer follow-up procedures
      showed to be based on weak evidence of effectiveness and to lack formal
      methodological approaches. In general, such literature is quite recent, relies on
      small sample observational studies, and suffers from a lack of financial support.
      CONCLUSIONS: There are few available lights in economic considerations on
      gynecologic cancer follow-up, represented by all the published studies, and many
      shadows that require to be clarified by properly designed randomized trials
      including cost-effectiveness analysis.

PMID- 25950133
TI  - Occurrence, behavior and human health risk assessment of dechlorane plus and
      related compounds in indoor dust of China.
AB  - Levels of dechlorane plus (DP) and "DP-like" compounds were measured in indoor
      dust samples collected across China. The concentrations of SigmaDP and "DP-like"
      compounds ranged from 0.35 to 1,000 ng g(-1) and<0.21 to 2.4 ng g(-1),
      respectively. The total DP concentration in urban sites were significantly higher
      than those of rural sites, while no significant difference was found for "DP
      like" compounds, suggesting different sources of these compounds. Significant
      positive correlations were found between fsyn and latitude, and between fsyn and
      longitude. The deleterious risk associated with DP exposure via indoor dust for
      the general population in China was low and safer than expectation. For
      estimating human exposure via indoor dust, sensitivity analysis showed that more
      attention should be given to the influential variables such as the level of
      pollutants, body weight, and the amount of ingestion and adsorption.

PMID- 25950134
TI  - Accumulation and oxidation of elemental mercury in tropical soils.
AB  - The role of chemical and mineralogical soil properties in the retention and
      oxidation of atmospheric mercury in tropical soils is discussed based on thermal
      desorption analysis. The retention of gaseous mercury by tropical soils varied
      greatly both quantitatively and qualitatively with soil type. The average natural
      mercury content of soils was 0.08 +/- 0.06 MUg g(-1) with a maximum of 0.215 +/-
      0.009 MUg g(-1). After gaseous Hg(0) incubation experiments, mercury content of
      investigated soils ranged from 0.6 +/- 0.2 to 735 +/- 23 MUg g(-1), with a mean
      value of 44 +/- 146 MUg g(-1). Comparatively, A horizon of almost all soil types
      adsorbed more mercury than B horizon from the same soil, which demonstrates the
      key role of organic matter in mercury adsorption. In addition to organic matter,
      pH and CEC also appear to be important soil characteristics for the adsorption of
      mercury. All thermograms showed Hg(2+) peaks, which were predominant in most of
      them, indicating that elemental mercury oxidized in tropical soils. After four
      months of incubation, the thermograms showed oxidation levels from 70% to 100%.
      As none of the samples presented only the Hg(0) peak, and the soils retained
      varying amounts of mercury despite exposure under the same incubation conditions,
      it became clear that oxidation occurred on soil surface. Organic matter seemed to
      play a key role in mercury oxidation through complexation/stabilization of the
      oxidized forms. The lower percentages of available mercury (extracted with KNO3)
      in A horizons when compared to B horizons support this idea.

PMID- 25950135
TI  - Effect of dispersed crude oil on cardiac function in seabass Dicentrarchus
      labrax.
AB  - In this study, the impact of dispersed oil was assessed in Dicentrarchus labrax,
      a fish frequently used as an oil contamination indicator species. Fish were
      exposed for 48h to (mechanically and chemically) dispersed oil and dispersant
      alone. The impact of these exposure conditions was assessed on cardiac function
      by measuring (i) the contraction strength, the contraction and the relaxation
      speeds (ii) the cardiac energy metabolism using respirometry on permeabilized
      cardiac fibers. Compared to control, the increase of polycyclic aromatic
      metabolites observed in the bile indicated oil contamination in our fish.
      Following 48h of oil exposure at realistic oil concentrations, alterations of
      cardiac performances were observed. A decrease in contraction strength,
      contraction and relaxation speeds was observed in the presence of oil without
      effect of dispersant on these three parameters. Looking at cardiac energy
      metabolism, dispersant alone decreases all the activity of the respiratory chain
      and increases the proton leak. From these results, it appears that the observed
      decrease in cardiac performance in fish exposed to oil was not linked to a
      decrease in energy availability. 

PMID- 25950136
TI  - Measuring air-water interfacial area for soils using the mass balance surfactant
      tracer method.
AB  - There are several methods for conducting interfacial partitioning tracer tests to
      measure air-water interfacial area in porous media. One such approach is the mass
      balance surfactant tracer method. An advantage of the mass-balance method
      compared to other tracer-based methods is that a single test can produce multiple
      interfacial area measurements over a wide range of water saturations. The mass
      balance method has been used to date only for glass beads or treated quartz sand.
      The purpose of this research is to investigate the effectiveness and
      implementability of the mass-balance method for application to more complex
      porous media. The results indicate that interfacial areas measured with the mass
      balance method are consistent with values obtained with the miscible-displacement
      method. This includes results for a soil, for which solid-phase adsorption was a
      significant component of total tracer retention. 

PMID- 25950137
TI  - Temporal and spatial variability of trace volatile organic compounds in
      rainwater.
AB  - This study presents the first detailed concentration profile of trace VOCs in
      atmospheric waters. Analytes were detected and quantified in 111 unique rain
      events in Wilmington, NC, USA over a one-year period. Headspace solid phase
      microextraction was optimized for detection of these compounds at sub-nanomolar
      levels. Distinct seasonality in both the occurrence and concentration of
      compounds was observed with the lowest abundance occurring during low irradiance
      winter months. In contrast to other rainwater components studied at this
      location, VOCs did not show any correlation between rainfall amount and
      concentrations. There was significant spatial variation with regards to air-mass
      back-trajectory for methyfuran with higher concentrations observed in terrestrial
      events during the growing season. Air mass back trajectory also impacted CCl4
      concentrations in rainwater with evidence of a possible oceanic input. However
      there was no significant impact of air-mass back-trajectory on the concentration
      of BTEX observed in rain indicating that storm origin is not the controlling
      factor driving concentrations of these analytes in precipitation. Members of the
      BTEX family did, however, have significant correlations with each other occurring
      in ratios aligned closely with ratios reported in the literature for gas-phase
      BTEX. Using available gas-phase data from locations with similar anthropogenic
      sources and Henry's Law constants, calculated concentrations agreed with VOC
      levels found in Wilmington rain. Results of this study indicate local gas-phase
      scavenging is the major source of VOCs in rain and wet deposition is not an
      efficient removal mechanism (<0.1%) of VOCs from the atmosphere. 

PMID- 25950138
TI  - Biochemical responses in mussels Perna perna exposed to diesel B5.
AB  - In Brazil B5 blend (5% biodiesel and 95% diesel oil) has been adopted as
      mandatory fuel since 2010 for automotive vehicles. Since little is known about
      the effects of B5 exposure can promote on antioxidant system of marine biota this
      study aimed to assess if B5 can generate modifications in antioxidant parameters
      of mussels Perna perna. To address this question mussels were exposed to two
      concentrations of B5 (0.01 mL L(-1) and 0.1 mL L(-1)) for 6h, 12h, 48 h and 168
      h. Then the activity of superoxide dismutase (SOD), catalase (CAT), glutathione
      peroxidase (GPx), glutathione S-transferase (GST) and glutathione reductase (GR)
      were evaluated in gills and digestive gland as well as the contents of
      glutathione (GSH) and lipid peroxidation by measuring the malondialdehyde
      concentration (MDA). In the gills, GST activity decreased after 48 h and GR after
      12h of exposure to B5. In digestive glands, the activities of SOD, GPx and GR
      were changed due to treatments. GSH concentration increased in digestive gland
      after 6h and 12h and in gills after 48 h for B5 0.1 mL L(-1) and after 168 h in
      the digestive gland for B5 0.01 mL L(-1) treatment. No lipid peroxidation was
      detected. The integrated biomarker response index (IBR) evidenced a B5 effect in
      the digestive gland after 168 h of exposure. Regarding the experimental
      conditions and species used in this study, long-term exposure to B5 is apparently
      more likely to affect the parameters tested in P. perna mussels.

PMID- 25950139
TI  - Thoracic Neurilemmoma Presenting With Spinal Nerve Involvement in Promyelocytic
      Leukemia.

PMID- 25950140
TI  - Promoting Weight Maintenance among Overweight and Obese Hispanic Children in a
      Rural Practice.
AB  - BACKGROUND: US Hispanic children experience a disproportionate burden of
      overweight and obesity. Comprehensive high-intensity behavioral programs have
      demonstrated effectiveness in improving weight status among obese children.
      However, there remains a need to develop more efficient interventions that are
      feasible in primary care and demonstrate effectiveness in Hispanic children.
      METHODS: The pilot study used a two-group randomized design. Eligible overweight
      (BMI between the 85th and 94th percentile for age and gender) or obese (BMI
      >=95th percentile) Hispanic children and their parents (N=118 child/parent dyads)
      were recruited from a rural pediatric clinic and randomized to: standard care
      (SC; n=61 dyads) or behavioral intervention (INT; n=57 dyads). The primary
      outcomes-weight, waist circumference, and zBMI-were measured at baseline, 2, 6,
      and 18 weeks. Multivariate logistic regression was used to examine the effect of
      INT on the likelihood of weight maintenance adjusting for potential confounding
      variables. RESULTS: Significantly fewer INT children (68.5%) experienced weight
      gain, compared to SC children (89.7%; p=0.009). The same pattern was observed for
      waist circumference, where fewer INT children (44%) experienced an increase in
      waist circumference, compared to SC children (68.6%; p=0.02). Although a trend of
      improvement in favor of the INT was observed for zBMI, it was not significant.
      CONCLUSIONS: This study provides preliminary evidence for the feasibility of a
      primary-care-based approach to promoting weight maintenance among a high-risk
      population.

PMID- 25950142
TI  - Survey of duckweed diversity in Lake Chao and total fatty acid, triacylglycerol,
      profiles of representative strains.
AB  - Lemnaceae (duckweeds) are widely distributed aquatic flowering plants. Their high
      growth rate, starch content and suitability for bioremediation make them
      potential feedstock for biofuels. However, few natural duckweed resources have
      been investigated in China, and there is no information about total fatty acid
      (TFA) and triacylglycerol (TAG) composition of duckweeds from China. Here, the
      genetic diversity of a natural duckweed population collected from Lake Chao,
      China, was investigated using multilocus sequence typing (MLST). The 54 strains
      were categorised into four species in four genera, representing 12 distinct
      sequence types. Strains representing Lemna aequinoctialis and Spirodela polyrhiza
      were predominant. Interestingly, a surprisingly high degree of genetic
      diversification within L. aequinoctialis was observed. The four duckweed species
      revealed a uniform fatty acid composition, with three fatty acids, palmitic acid,
      linoleic acid and linolenic acid, accounting for more than 80% of the TFA. The
      TFA in biomass varied among species, ranging from 1.05% (of dry weight, DW) for
      L. punctata and S. polyrhiza to 1.62% for Wolffia globosa. The four duckweed
      species contained similar TAG contents, 0.02% mg . DW(-1). The fatty acid
      profiles of TAG were different from those of TFA, and also varied among the four
      species. The survey investigated the genetic diversity of duckweeds from Lake
      Chao, and provides an initial insight into TFA and TAG of four duckweed species,
      indicating that intraspecific and interspecific variations exist in the content
      and composition of both TFA and TAG in comparison with other studies.

PMID- 25950143
TI  - Influence of structural defects and oxidation onto hole conductivity in P3HT.
AB  - The effect of structural imperfections as well as oxygen impurities on the
      quantum conductance of poly(3-hexylthiophene) is calculated from first-principles
      by solving the scattering problem for molecular structures obtained within
      density functional theory. It is shown that the conductivity of molecular
      crystals perpendicular to the polymer chains depends strongly on the stacking
      geometry and is roughly described within the Wentzel-Kramers-Brillouin
      approximation. Furthermore, it is found that local relaxation for twisted or bent
      polymer chains efficiently restores the conductance that drops substantially for
      sharp kinks with curvature radii smaller than 17 A and rotations in excess of ~60
      degrees . In contrast, isomer defects in the coupling along the chain direction
      are of minor importance for the intrachain transmission. Also, oxidation of the
      side chains as well as molecular sulfur barely changes the coherent transport
      properties, whereas oxidation of thiophene group carbon atoms drastically reduces
      the conductance. 

PMID- 25950141
TI  - Experimental hepatocyte xenotransplantation--a comprehensive review of the
      literature.
AB  - Hepatocyte transplantation (Tx) is a potential therapy for certain diseases of
      the liver, including hepatic failure. However, there is a limited supply of human
      livers as a source of cells and, after isolation, human hepatocytes can be
      difficult to expand in culture, limiting the number available for Tx. Hepatocytes
      from other species, for example, the pig, have therefore emerged as a potential
      alternative source. We searched the literature through the end of 2014 to assess
      the current status of experimental research into hepatocyte xenoTx. The
      literature search identified 51 reports of in vivo cross-species Tx of
      hepatocytes in a variety of experimental models. Most studies investigated the Tx
      of human (n = 23) or pig (n = 19) hepatocytes. No studies explored hepatocytes
      from genetically engineered pigs. The spleen was the most common site of Tx (n =
      23), followed by the liver (through the portal vein [n = 6]) and peritoneal
      cavity (n = 19). In 47 studies (92%), there was evidence of hepatocyte
      engraftment and function across a species barrier. The data provided by this
      literature search strengthen the hypothesis that xenoTx of hepatocytes is
      feasible and potentially successful as a clinical therapy for certain liver
      diseases, including hepatic failure. By excluding vascular structures,
      hepatocytes isolated from genetically engineered pig livers may address some of
      the immunological problems of xenoTx.

PMID- 25950144
TI  - Single-cell evaluation of red blood cell bio-mechanical and nano-structural
      alterations upon chemically induced oxidative stress.
AB  - Erythroid cells, specifically red blood cells (RBCs), are constantly exposed to
      highly reactive radicals during cellular gaseous exchange. Such exposure often
      exceeds the cells' innate anti-oxidant defense systems, leading to progressive
      damage and eventual senescence. One of the contributing factors to this process
      are alterations to hemoglobin conformation and globin binding to red cell
      cytoskeleton. However, in addition to the aforementioned changes, it is possible
      that oxidative damage induces critical changes to the erythrocyte cytoskeleton
      and corresponding bio-mechanical and nano-structural properties of the red cell
      membrane. To quantitatively characterize how oxidative damage accounts for such
      changes, we employed single-cell manipulation techniques such as micropipette
      aspiration and atomic force microscopy (AFM) on RBCs. These investigations
      demonstrated visible morphological changes upon chemically induced oxidative
      damage (using hydrogen peroxide, diamide, primaquine bisphosphate and cumene
      hydroperoxide). Our results provide previously unavailable observations on
      remarkable changes in red cell cytoskeletal architecture and membrane stiffness
      due to oxidative damage. Furthermore, we also demonstrate that a pathogen that
      infects human blood cells, Plasmodium falciparum was unable to penetrate through
      the oxidant-exposed RBCs that have damaged cytoskeleton and stiffer membranes.
      This indicates the importance of bio-physical factors pertinent to aged RBCs and
      it's relevance to malaria infectivity. 

PMID- 25950145
TI  - Electrolyte Mixtures Based on Ethylene Carbonate and Dimethyl Sulfone for Li-Ion
      Batteries with Improved Safety Characteristics.
AB  - In this study, novel electrolyte mixtures for Li-ion cells are presented with
      highly improved safety features. The electrolyte formulations are composed of
      ethylene carbonate/dimethyl sulfone (80:20 wt/wt) as the solvent mixture and
      LiBF4 , lithium bis(trifluoromethanesulfonyl)azanide, and lithium
      bis(oxalato)borate as the conducting salts. Initially, the electrolytes are
      characterized with regard to their physical properties, their lithium transport
      properties, and their electrochemical stability. The key advantages of the
      electrolytes are high flash points of >140  degrees C, which enhance
      significantly the intrinsic safety of Li-ion cells containing these electrolytes.
      This has been quantified by measurements in an accelerating rate calorimeter. By
      using the newly developed electrolytes, which are liquid down to T=-10  degrees
      C, it is possible to achieve C-rates of up to 1.5 C with >80 % of the initial
      specific capacity. During 100 cycles in cell tests (graphite||LiNi1/3 Co1/3 Mn1/3
      O2 ), it is proven that the retention of the specific capacity is >98 % of the
      third discharge cycle with dependence on the conducting salt. The best
      electrolyte mixture yields a capacity retention of >96 % after 200 cycles in coin
      cells. 

PMID- 25950146
TI  - Trap-Free Halogen Photoelimination from Mononuclear Ni(III) Complexes.
AB  - Halogen photoelimination reactions constitute the oxidative half-reaction of
      closed HX-splitting energy storage cycles. Here, we report high-yielding,
      endothermic Cl2 photoelimination chemistry from mononuclear Ni(III) complexes. On
      the basis of time-resolved spectroscopy and steady-state photocrystallography
      experiments, a mechanism involving ligand-assisted halogen elimination is
      proposed. Employing ancillary ligands to promote elimination offers a strategy to
      circumvent the inherently short-lived excited states of 3d metal complexes for
      the activation of thermodynamically challenging bonds. 

PMID- 25950147
TI  - Fast iterative pre-emphasis calibration method enabling third-order dynamic shim
      updated fMRI.
AB  - PURPOSE: To calibrate a pre-emphasis to sufficiently compensate eddy currents for
      application of dynamic shim updating to fMRI without extension of scan times.
      METHODS: Eddy current effects induced into all shim terms up to third-order were
      characterized by spatiotemporal field monitoring, using a third-order field
      camera. Pre-emphasis settings were derived from the measurements and iteratively
      evaluated and refined. The calibrated pre-emphasis was applied to slice-wise
      dynamic shim updating in combination with a dynamic excitation frequency (F0)
      determination and a slice-wise B0 optimization routine for in vivo echo planar
      imaging and resting-state functional MRI. RESULTS: The described method for pre
      emphasis calibration led to settling times of remaining eddy current effects
      below 2 ms, allowing for the application of dynamic shim updating to fMRI without
      extension of scan times or induction of eddy current related artifacts. A dynamic
      F0 determination compensates frequency shifts induced by the superposition of
      different shim fields, and therefore, prevents an image shift within the field of
      view. Hardware limitations necessitate the reduction of the maximum applicable B0
      shim field amplitudes and restrict the shim performance. CONCLUSION: The proposed
      method enables accurate pre-emphasis calibration, and therefore, the application
      of dynamic shim updating to fMRI.

PMID- 25950149
TI  - Unrest in Baltimore: The Role of Public Health.

PMID- 25950148
TI  - Correlations between drug resistance of Beijing/W lineage clinical isolates of
      Mycobacterium tuberculosis and sublineages: a 2009-2013 prospective study in
      Xinjiang province, China.
AB  - BACKGROUND: The prevalence of drug-resistant tuberculosis (TB) in Xinjiang is
      higher than in other regions of China, and Beijing/W lineage Mycobacterium
      tuberculosis (MTB) is the dominant strain of MTB in Xinjiang. However,
      information on multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB,
      particularly the correlation between MDR and the Beijing/W lineage and the
      correlation between drug resistance and the Beijing/W sublineage strains, is
      limited. MATERIAL/METHODS: We conducted a prospective study to describe the
      prevalence of MDR/XDR TB, Beijing/W lineage and sublineage strains in Xinjiang in
      China from 2009 to 2013. All MTB underwent drug susceptibility testing to the
      first- and second-line anti-tuberculosis drugs. The Beijing/W lineages and
      sublineages were detected by large-sequence polymorphisms with polymerase chain
      reaction. RESULTS: A total of 410 clinical isolates were identified. The overall
      percentage of MDR and XDR cases in Xinjiang was 13.2% (54/410) and 13.0% (7/54),
      respectively. Overall, 9.8% (14/143) of the Beijing lineage MTB were MDR
      patients, and 15.6% (40/257) of the Non-Beijing lineage MTB were MDR patients. In
      the 143 Beijing MTB lineages, 11.2% isolates were in sublineage 105, 15.4%
      isolates were in sublineage 207, 69.2% isolates were in sublineage 181, and 4.2%
      isolates were in sublineage 150. None of the isolates were detected in sublineage
      142. Significant differences between the Beijing/W and non-Beijing/W strains were
      observed regarding INH and EMB resistance, respectively. CONCLUSIONS: The
      prevalence of the MDR TB in Xinjiang remains high and imposes challenges for TB
      control. Four Beijing/W sublineage isolates were observed in Xinjiang. There was
      no correlation between MDR and the Beijing/W lineage and no correlation between
      drug resistance and the Beijing/W sublineage strains. Surveillance of the
      clinical isolates of MTB is recommended to strengthen the identification of
      MDR/XDR TB and sublineages of the Beijing/W strains.

PMID- 25950150
TI  - Normative Data on the Beck Depression Inventory--Second Edition (BDI-II) in
      College Students.
AB  - OBJECTIVE: This study was conducted to provide normative data on the Beck
      Depression Inventory--Second Edition (BDI-II) in college students. METHOD: Data
      were obtained from 15,233 college students drawn from 17 universities in the
      United States, weighted to match the gender and race/ethnicity of enrollment in
      degree-granting institutions. RESULTS: Descriptive statistics, point prevalence
      of individuals exceeding cutoff scores, and mean differences by gender and
      race/ethnicity were provided. Because the distribution of BDI-II scores was not
      normal, percentile ranks for raw scores were provided for the total sample and
      separately by gender and race/ethnicity for the total sample and by
      race/ethnicity for men and women. Normative data were used to calculate the
      Reliable Change Index on the BDI-II for college students. CONCLUSION: Because the
      distribution of BDI-II scores demonstrated significant skewness and non-normal
      kurtosis, percentile ranks are important to consider in interpreting scores on
      the measure, in addition to descriptive statistics.

PMID- 25950151
TI  - Adiposity is related to decrements in cardiorespiratory fitness in obese and
      normal-weight children.
AB  - BACKGROUND: Obese children are typically less physically active than their normal
      weight peers and are often assumed to be 'unfit'. OBJECTIVE: Investigate the
      relationships between adiposity, physical activity levels and cardiorespiratory
      fitness (CRF) in obese and normal-weight children. A secondary aim was to examine
      obese/normal-weight differences in CRF. METHODS: Obese (N = 107) and normal
      weight (N = 132) 10-13-year-olds participated. Fat-free mass (FFM), percent fat,
      physical activity and peak oxygen uptake (VO2peak ) were assessed. Analyses were
      adjusted for socioeconomic status (SES). RESULTS: Higher percent fat was
      inversely associated with VO2peak normalized for mass (r = -0.780, P < 0.001)
      even after controlling for physical activity (r = -0.673, P < 0.001). While
      higher percent fat was also inversely associated with VO2peak normalized for FFM,
      this was only significant in males (r = -0.247, P = 0.004) and did not persist
      after controlling for physical activity (r = -0.059 P = 0.526). Compared with
      normal-weight children, obese children had higher absolute VO2peak , lower
      VO2peak corrected for mass (P <= 0.009) and lower VO2peak corrected for FFM (P =
      0.041) that did not persist after controlling for SES (P = 0.086). CONCLUSION:
      Obesity-related inefficiencies in CRF were evident. Higher adiposity was
      associated with poorer CRF relative to mass, irrespective of physical activity
      levels. However, low physical activity levels may be responsible for associations
      between adiposity and CRF relative to FFM seen in boys, indicating the importance
      of encouraging physical activity.

PMID- 25950153
TI  - Finger-gate manipulated quantum transport in Dirac materials.
AB  - We investigate the quantum transport properties of multichannel nanoribbons made
      of materials described by the Dirac equation, under an in-plane magnetic field.
      In the low energy regime, positive and negative finger-gate potentials allow the
      electrons to make intra-subband transitions via hole-like or electron-like
      quasibound states (QBS), respectively, resulting in dips in the conductance. In
      the high energy regime, double dip structures in the conductance are found,
      attributed to spin-flip or spin-nonflip inter-subband transitions through the
      QBSs. Inverting the finger-gate polarity offers the possibility to manipulate the
      spin polarized electronic transport to achieve a controlled spin-switch. 

PMID- 25950152
TI  - Far-Red and Near-IR AIE-Active Fluorescent Organic Nanoprobes with Enhanced Tumor
      Targeting Efficacy: Shape-Specific Effects.
AB  - The rational design of high-performance fluorescent materials for cancer
      targeting in vivo is still challenging. A unique molecular design strategy is
      presented that involves tailoring aggregation-induced emission (AIE)-active
      organic molecules to realize preferable far-red and NIR fluorescence, well
      controlled morphology (from rod-like to spherical), and also tumor-targeted
      bioimaging. The shape-tailored organic quinoline-malononitrile (QM) nanoprobes
      are biocompatible and highly desirable for cell-tracking applications.
      Impressively, the spherical shape of QM-5 nanoaggregates exhibits excellent tumor
      targeted bioimaging performance after intravenously injection into mice, but not
      the rod-like aggregates of QM-2. 

PMID- 25950155
TI  - Removal of Phenol by A. belladonna L. Hairy Root.
AB  - Phenolic compounds that present in the several industries are harmful and
      dangerous for human health. In this study we have studied the potential of Atropa
      belladonna hairy roots in phenol removal of wastewater. The optimal conditions
      for the removal process were evaluated using different phenol (10-500 mg.1(-1))
      and H2O2 (1-15 Mm) concentrations. In the presence of H2O2, Roots were able to
      remove phenol concentrations up to 500 mg.1(-1). in the wide range of pH (4-9),
      reaching high removal efficiency. When roots were re-used for five consecutive
      cycles, phenol removal efficiency decreased from 98-62%, in the last cycle. After
      the removal process, the solutions were obtained from the experiment were
      estimated for their toxicity using a test with Lactaca sativa L. seeds. Results
      showed that the treated solution was less toxic than the parent solution. 

PMID- 25950154
TI  - Photoelectrocyclization as an activation mechanism for organelle-specific live
      cell imaging probes.
AB  - Photoactivatable fluorophores are useful tools in live-cell imaging owing to
      their potential for precise spatial and temporal control. In this report, a new
      photoactivatable organelle-specific live-cell imaging probe based on a 6pi
      electrocyclization/oxidation mechanism is described. It is shown that this new
      probe is water-soluble, non-cytotoxic, cell-permeable, and useful for
      mitochondrial imaging. The probe displays large Stokes shifts in both pre
      activated and activated forms, allowing simultaneous use with common dyes and
      fluorescent proteins. Sequential single-cell activation experiments in dense
      cellular environments demonstrate high spatial precision and utility in single-
      or multi-cell labeling experiments. 

PMID- 25950156
TI  - A Cytostatic Ruthenium(II)-Platinum(II) Bis(terpyridyl) Anticancer Complex That
      Blocks Entry into S Phase by Up-regulating p27(KIP1).
AB  - Cytostatic agents that interfere with specific cellular components to prevent
      cancer cell growth offer an attractive alternative, or complement, to traditional
      cytotoxic chemotherapy. Here, we describe the synthesis and characterization of a
      new binuclear Ru(II) -Pt(II) complex [Ru(tpy)(tpypma)Pt(Cl)(DMSO)](3+)
      (tpy=2,2':6',2''-terpyridine and tpypma=4-([2,2':6',2''-terpyridine]-4'-yl)-N
      (pyridin-2-ylmethyl)aniline), VR54, which employs the extended terpyridine tpypma
      ligand to link the two metal centres. In cell-free conditions, VR54 binds DNA by
      non-intercalative reversible mechanisms (Kb =1.3*10(5)  M(-1) ) and does not
      irreversibly bind guanosine. Cellular studies reveal that VR54 suppresses
      proliferation of A2780 ovarian cancer cells with no cross-resistance in the
      A2780CIS cisplatin-resistant cell line. Through the preparation of mononuclear
      Ru(II) and Pt(II) structural derivatives it was determined that both metal
      centres are required for this anti-proliferative activity. In stark contrast to
      cisplatin, VR54 neither activates the DNA-damage response network nor induces
      significant levels of cell death. Instead, VR54 is cytostatic and inhibits cell
      proliferation by up-regulating the cyclin-dependent kinase inhibitor p27(KIP1)
      and inhibiting retinoblastoma protein phosphorylation, which blocks entry into S
      phase and results in G1 cell cycle arrest. Thus, VR54 inhibits cancer cell growth
      by a gain of function at the G1 restriction point. This is the first metal
      coordination compound to demonstrate such activity. 

PMID- 25950157
TI  - Differential reactivity of salivary igA and igG against streptococcus mutans
      proteins in humans with different caries experience.
AB  - Dental caries is an infectious disease which still constitutes a public health
      concern. It begins at an early age and is caused mainly Streptococcus mutans (S.
      mutans). The aim of this study was to characterize the salivary humor immune
      response to S. mutans proteins in patients with caries, with history of caries
      and without caries, in order to determine which S. mutans proteins participate in
      the immunological response in subjects with different caries experience. Saliva
      was collected by spontaneous salivation for 5 minutes from 60 subjects aged 18 to
      30 years, classified according to their caries experience as: without caries
      (Group I), with active caries (Group II) and with history of caries (Group III).
      The antigens derived from S. mutans by sonication were recognized by salivary IgA
      and IgG by Western Blot. The results showed that all the individuals studied
      recognized S. mutans proteins with molecular weights in the range of 8 to 191
      kDa, with similar recognition profiles for salivary IgA and IgG. Subjects without
      caries recognized the 29 kDa protein, also known as S. mutans Antigen A, via
      salivary IgA, differing from patients with caries and history of caries, who
      recognized it via IgG. The protective response against S. mutans is mediated by
      IgA. To conclude, a differential response to the 29 kDa protein between study
      individuals may be indicative of resistance to dental caries and may have a
      protective role in the induction of IgA antibodies against dental caries, as
      found in the group without caries, in contrast to subjects with active caries and
      history of caries. 

PMID- 25950158
TI  - Dental status and dental treatment demands in preschoolers from urban and
      underprivileged urban areas in Mendoza city, Argentina.
AB  - The aim of this study was to establish the association between dental status and
      demand for dental care in preschoolers at urban and underprivileged urban schools
      in the city of Mendoza. Dental status was diagnosed in a purposive sample of
      preschoolers at urban schools (Group U: n = 148) and underprivileged urban
      schools (Group UnU: n = 155) in Greater Mendoza city, by determining the
      following indicators: (a) caries-free children (%), and (b) dmft/DMFT and its
      discriminated components, including active non-cavitated enamel caries. The
      characteristics of demand for care were determined using an ad hoc structured
      questionnaire. The following were determined: frequency distributions and
      confidence intervals for categorical variables, measures of central tendency and
      dispersion, tests for differences in means (Student's t test), association (chi
      squared) and correlation among variables (Pearson's r), at a significance level
      p<0.05. Comparison of dental status variables between groups showed significantly
      higher values in group UnU for: d+D tooth (x = 5.4} 3.8; t = 2.887; p = 0.004);
      dmft+DMFT (x = 5.7}4.1; t = 0.466; p = 0.020); d+D surface (x = 7.62} 6.2; t =
      0.956; p = 0.014); f+F surface (x = 0.12}4.5; t = 2.71; p = 0.007) and percentage
      of caries-free children (x2= 25.377; p= 0.018). The following trends were found
      in this group: higher demand on the government subsystem, fewer visits to the
      dentist (x2 = 7.02, p = 0.008) and greater difficulty in getting appointments (x2
      = 19.91, px0.001). Frequency of visits was associated to the severity of dental
      status (x2 = 19.412; px0.001), but no correlation was found between frequency of
      visits during the past year and dmft+DMFT (Pearson's r coefficient = 0.091; p =
      0.0426) Group U showed preferential demand for the private or "obra social"
      (trade union managed health insurance) systems (x2 = 78.85 p = 0.00) and there
      was no statistically significant association between visits to the dentist and
      dmft+DMFT categories (x2 = 2.781; p = 0.427), although there was direct
      correlation between frequency of visits during the past year and dmft+DMFT
      (Pearson's r coefficient = 0.486, p = 0.000). Preschoolers at UnU schools had
      higher caries indicators than preschoolers at U schools. For UnU the demand for
      care was related to the severity of dental status and situations of urgency,
      while U preschoolers demanded dental care in both health and disease, with a
      tendency to greater adherence to treatment. Actions to promote oral health in
      preschoolers should take into account both internal and external barriers to
      access to and use of oral health services. 

PMID- 25950159
TI  - The influence of maxillary and mandibular osteoporosis on maximal bite force and
      thickness of masticatory muscles.
AB  - The aim of this study was to examine the bite force and masseter and temporal
      muscle thickness in individuals with maxillary and mandibular osteoporosis. 72
      individuals were distributed into two equal groups: (1) facial osteoporosis and
      (2) healthy controls. Bite force on the right and left molar regions was recorded
      with a dynamometer and the highest value out of three measurements was recorded
      as the maximal bite force. Muscle thickness was measured with a SonoSite Titan
      ultrasound scanner. Ultrasound images were obtained of the bilateral masseter and
      temporal muscles at rest and at maximal voluntary contraction. The means of the
      measurements in each clinical condition were analyzed with multivariate
      statistical analysis (SPSS 19.0). Student's t test indicated no significant
      difference for muscle thickness, but indicated significantly lower bite force
      values in the osteoporosis group (p>0.05). Lower bite force in individuals with
      facial bone loss demonstrates functional impact of osteoporosis on the complex
      physiological stomatognathic system. 

PMID- 25950160
TI  - Do resin cements influence the cuspal deflection of teeth restored with composite
      resin inlays?
AB  - The aim of this study was to evaluate the influence of different resin cements on
      the cuspal deflection of endodontically treated teeth restored with composite
      resin inlays. Sixty upper premolars were randomly divided into five groups
      (n=12): 1 - sound teeth; 2 - cavity; 3 - Rely X ARC; 4 - RelyX Unicem; 5 - SeT.
      The teeth from groups 2, 3, 4 and 5 received a MOD preparation and endodontic
      treatment. Impressions were made with vinyl polysiloxane and poured using type IV
      die stone in groups 3, 4 and 5. Inlays with composite resin were built over each
      cast and luted with the resin cements. A 200 N load was applied on the occlusal
      surface, and cuspal deflection was measured using a micrometer. After 24 h,
      cuspal deflection was measured again using a 300 N load. The Student t-test
      showed that there was no statistically significant difference between the 200 N
      and 300 N occlusal loads only for the sound teeth group (p = 0.389) and the RelyX
      ARC group (p = 0.188). ANOVA and Tukey'test showed that the sound teeth had the
      lowest mean cuspal deflection, differing statistically from the other groups
      (p<0.05). The highest cuspal deflections were obtained in the SeT group and the
      cavity group, with no statistical difference between them. Intermediate values
      were obtained in RelyX ARC group and RelyX Unicem group, which differed
      statistically. The self-adhesive resin cements RelyX Unicem and SeT showed less
      capacity to maintain the stiffness of the tooth/restoration complex than the
      conventional resin cement RelyX ARC. 

PMID- 25950161
TI  - Social representat ions of dental treatment in a group of environmental health
      graduate students in Lima (Peru).
AB  - Social representations are a type of common sense knowledge shared by different
      groups based on their experience. This study identified the social
      representations of dental practice in a group of environmental health graduate
      students in Lima, Peru. METHOD: We interviewed 25 graduate students using a
      "focus group" technique and a semi-structured guide. Three groups were formed
      with purposive sampling. The data were collected during the years 2010-2011, and
      analyzed using open, axial, selective coding with Atlas-Ti software. RESULTS:
      Three substantive categories were identified: dental practice, characteristics of
      the dental care provider and dental practice setting. The social representations
      that the students identified with dental practice were fear and pain.
      CONCLUSIONS: The negative social representations of dental practice may affect
      viability and adherence to treatment, so it is important to identify them in time
      in order to intervene effectively.

PMID- 25950162
TI  - Titanium alloy orthodontic mini-implants: scanning electron microscopic and
      metallographic analyses.
AB  - Anchorage control is one of the determining factors of successful orthodontic
      mechanics. In mini-implants, fractures due to placement and removal have been
      related to implant design and titanium alloy quality. This study assessed the
      topography and microstructure of five brands of mini-implants (Neodent, SIN,
      Morelli, Conexao, Foresta Dent). Scanning electron microscopic analyses of the
      head, transmucosal neck, threaded body, and tip were performed to assess implant
      design and manufacturing defects (n=3/group). Metallographic analysis of
      longitudinal sections (n=15) and cross-sections (n=15) was performed under
      conventional light microscopy according to international standards of "American
      Society for Testing and Materials". The results showed significant differences in
      miniimplant design. Surface irregularities in the threaded body and tip were
      observed. Microstructural analyses revealed an alpha/beta-phase grain structure,
      in compliance with the ETTC-2 ("Technical Committee of European Titanium
      Producers" -2nd edition). No structural defects were detected. We conclude that
      differences in mini-implant design and the presence of surface irregularities may
      influence the effectiveness of orthodontic anchorage. 

PMID- 25950163
TI  - Oral health in drug addict adolescents and non psychoactive substance users.
AB  - The purpose of this study was to compare oral health between adolescents who are
      recovering drug addicts and adolescents who report not having used psychoactive
      substances. A retrospective observational Case-Control study was conducted on 60
      subjects per group, aged 15 to 25 years, paired according to sex, age and
      educational vulnerability. Dental and sialochemical examinations were used to
      determine oral health/disease/care indicators. Psychoactive substance use habits
      were obtained from clinical records. DMFT index for Case adolescents was
      8.58}4.34, doubling the mean value for the Control group, which was 4.33}4.30.
      CPI was compatible with gingival-periodontal health in 45% of the Control
      subjects, but only 20% in the Case group. CPI categories 2 and 3 had different
      distributions according to the study group, with CPI2=33%, CPI3=0% for the case
      group and CPI2=57%; CPI3=5% for the control group. Mean values for stimulated
      saliva for Case and Control groups, respectively, were: salivary flow (ml/min)
      1.42}1.08; 0.98}0.41, salivary pH 6.96}0.33 6.86}0.27, and buffer capacity
      expressed as final pH, 6.73}0.29, 6.61}0.28. Wilcoxon's test for independent
      samples showed significant differences (p<0.05) between Case and Control for the
      variables White Spot, Non-Cavitated Carious Lesions, Cavitated Carious Lesions,
      DMFT, Components D and M, Salivary Flow and Buffer Capacity. There was
      significant association between the D component in DMFT and use of psychoactive
      substances, both in single drug and polydrug users. Oral component status was
      worse in recovering drug addicts than in non-users of psychoactive substances. 

PMID- 25950165
TI  - Influence of polishing protocol on flexural properties of several dental
      composite resins.
AB  - The aim of this study was to determine the influence of the finishing protocol
      (FP) on flexural properties of several composites (CR). Twenty composite samples
      (25x2x2 mm) were prepared: G1 HelimolarR; G2 FiltekTM Z350;G3TetricR N Ceram, G4
      Point 4TM, G5 PremisaTM; G6 Esthet.XR HD, G7 ice, G8 Vit-L-escenceR, G9 GrandioR,
      G10 TPHR3, G11 AmelogenR Plus, G12 Brilliant Enamel; G13 FiltekTM Z100 and
      randomly divided into four groups according to the finishing system: C control, J
      JiffyR, SS Super SnapR, AA AstropolR /AstrobrushR. Each sample was polished for
      10 seconds with each sequence instrument, and stored in distilled water for 24
      hours, after which a three-point flexure test was applied to determine flexural
      strength (FS) and modulus (Flexural modulus). Data were analyzed using a two-way
      multivariate ANOVA and means were compared with Tukey's test. Results were: FS
      level CR p=0.000 with significant differences. FS level FPp= 0.093 with
      significant differences. In order: FM level CR p 0.00 with significant
      differences. FM level PS p=0.001; with significant differences. Under the study
      conditions, the polishing systems based on silicone rubber decreased the flexural
      properties of composite resins. 

PMID- 25950164
TI  - Perception of professionals in the assessment of coronoid hyperplasia by computed
      tomography.
AB  - Coronoid Hyperplasia (CH) is a non-neoplastic and relatively rare enlargement of
      the coronoid process that may limit mandibular movement as a consequence of the
      close association between the hyperplastic coronoid process and the anterior
      region of the zygomatic bone. Computed tomography (CT) is extremely useful for
      the observation of this association and plays an important role in diagnosing and
      planning surgical treatment. Once the CT scan is performed, the data can be
      viewed in many different arrangements, including multiplanar (MPR) and 3D
      rendering, although the resolution of the latter may not be as good as that of
      the former. Our aim is to analyze the importance of and preference for
      multiplanar and 3D reconstruction images for diagnosing and interpreting Coronoid
      Hyperplasia (CH), by comparing the opinions of oral surgeons and oral
      radiologists who analyzed both temporomandibular joints (TMJ) in 20 patients.
      Three images of each TMJ comprised the set of scans (MPR, 3D reconstructions with
      maximum intercuspation and 3D reconstructions with maximum mouth opening). After
      each analysis, the members of the two groups answered a questionnaire about the
      usefulness of each examination and classified the association between the head of
      mandible and mandibular fossa. Hypomotility was present in 55.2%. Both groups
      stated that both MPR and 3D reconstructions, particularly the latter, were
      fundamental for diagnosing CH and that they would request them in order to
      interpret CH correctly. The examiners were found to differ significantly
      regarding their opinion of MPR; only radiologists considered MPR to be less
      elucidative for the diagnosis of CH. 

PMID- 25950166
TI  - Influence of addition of 2-[3-(2H-benzotriazol-2-YL)- 4-hydroxyphenyl] ethyl
      methacrylate to an experimental adhesive system.
AB  - The aim of this study was to evaluate the addition of 2-[3-(2HBenzotriazol- 2-yl)
      4-hydroxyphenyl]ethyl methacrylate (BTAM) to an experimental adhesive resin. An
      experimental base adhesive resin was formulated with BisGMA, TEGDMA and HEMA, to
      which BTAM was added at 1, 2.5 and 5%, in weight. One group with no addition was
      used as control. The experimental adhesives were evaluated for antibacterial
      potential (against Streptococcus mutans), degree of conversion with FTIR,
      softening in solvent and microRaman interface analyses. Data were analyzed by
      Kruskal-Wallis, paired t test and ANOVA and Tukey, considering a 5% level of
      significance. The results showed antibacterial activity of 5% BTAM against S.
      mutans (p<0.05), however, no difference was found among BTAM groups (p> 0.05).
      The results of degree of conversion and softening of solvent showed no
      statistical difference between BTAM and control groups (p>0.05). The addition of
      5% BTAM showed higher antibacterial activity than the negative control, and
      copolymerization with comonomer blend of adhesive resin and BTAM was detected at
      the dentin/ adhesive interface. 

PMID- 25950167
TI  - Efficiency in bracket bonding with the use of pretreatment methods to tooth
      enamel before acid etching: sodium hypochlorite vs. hydrogen peroxide techniques.
AB  - Bond failures are produced by the existence of biofilm on the tooth surface.
      Because biofilm is impermeable, it prevents contact in many areas, reducing the
      etching effect which selectively dissolves calcified tissues but does not seem to
      eliminate biofilm from the tooth surface, and thus the bond between the tooth and
      the bracket is not strong enough. The aim of this study is to compare bracket
      bonding efficiency with two dental surface pretreatments: sodium hypochlorite vs.
      hydrogen peroxide techniques. This was a cross-sectional, comparative, in vitro
      study. Seventy-five premolars extracted for orthodontic purposes were evaluated.
      They were divided into three groups of 25 teeth and assigned randomly toone of
      the pretreatment techniques (5.25%sodium hypochlorite or 3.5% hydrogen peroxide)
      or to a control group. The most efficient pretreatment technique for bonding to
      brackets was sodium hypochlorite, with an average of 17.15 (kg/F). Significant
      differences were observed between groups (p=0.0001). The post hoc bond strength
      test showed statistically significant differences between the sodium hypochlorite
      technique and the control group (p=0.0001). The sodium hypochlorite technique
      improves bracket adhesion to tooth enamel. 

PMID- 25950168
TI  - Effect of dexamethasone on mandibular bone biomechanics in rats during the growth
      phase as assessed by bending test and peripheral quantitative computerized
      tomography.
AB  - Long-term glucocorticoid administration to growing rats induces osteopenia and
      alterations in the biomechanical behavior of the bone. This study was performed
      to estimate the effects of dexamethasone (DTX), a synthetic steroid with
      predominant glucocorticoid activity, on the biomechanical properties of the
      mandible of rats during the growth phase, as assessed by bending test and
      peripheral quantitative computed tomographic (pQCT) analysis. The data obtained
      by the two methods will provide more precise information when analyzed together
      than separately. Female rats aged 23 d (n=7) received 500MUg.kg-1 per day of DXT
      for 4 weeks. At the end of the treatment period, their body weight and body
      length were 51.3% and 20.6% lower, respectively, than controls. Hemimandible
      weight and area (an index of mandibular size) were 27.3% and 9.7% lower,
      respectively. The right hemimandible of each animal was subjected to a mechanical
      3-point bending test. Significant weakening of the bone, as shown by a
      correlative impairment of strength and stiffness, was observed in experimental
      rats. Bone density and cross-sectional area were measured by pQCT. Cross
      sectional, cortical and trabecular areas were reduced by 20% to 30% in the DTX
      group, as were other cortical parameters, including the bone density, mineral
      content and cross-sectional moment of inertia. The "bone strength index" (BSI,
      the product of the pQCT-assessed xCSMI and vCtBMD) was 56% lower in treated rats,
      which compares well with the 54% and 52% reduction observed in mandibular
      strength and stiffness determined through the bending test. Data suggest that the
      corticosteroid exerts a combined, negative action on bone geometry (mass and
      architecture) and volumetric bone mineral density of cortical bone, which would
      express independent effects on both cellular (material quality) and tissue (cross
      sectional design) levels of biological organization of the skeleton in the
      species. 

PMID- 25950169
TI  - Immunohistochemical and lectin histochemical studies on the developing olfactory
      organs of fetal camel.
AB  - Little is known about the development of the olfactory organs of camel. In this
      study, prenatal development and neuronal differentiation of the vomeronasal organ
      (VNO) and the olfactory epithelium (OE) of the one-humped camel were studied by
      immunohistochemistry and lectin histochemistry. A neuronal marker, protein gene
      product (PGP) 9.5, but not a marker of fully differentiated olfactory receptor
      cells, olfactory marker protein, intensely labeled the olfactory receptor cells
      of the VNO and OE at 395 mm, 510 mm, and 530 mm fetal ages, indicating that the
      olfactory receptor cells are differentiated, but not fully matured both in the
      VNO and the OE. In 187 mm and 190 mm fetuses, PGP 9.5 yielded faint
      immunoreactive signals in the VNO, but not in the OE, although the presence of
      olfactory receptor cells were demonstrated in both tissues by intense WGA and LEL
      stainings. We conclude that the camel VNO and OE bear differentiated, but still
      immature receptor cells; in addition, the onset of neuronal differentiation seems
      to be somewhat earlier in the VNO than in the OE till half of the prenatal life.

PMID- 25950170
TI  - Neuromuscular dysfunction in type 2 diabetes: underlying mechanisms and effect of
      resistance training.
AB  - Diabetic patients are at higher risk of developing physical disabilities than non
      diabetic subjects. Physical disability appears to be related, at least in part,
      to muscle dysfunction. Several studies have reported reduced muscle strength and
      power under dynamic and static conditions in both the upper and lower limbs of
      patients with type 2 diabetes. Additional effects of diabetes include a reduction
      in muscle mass, quality, endurance and an alteration in muscle fibre composition,
      though the available data on these parameters are conflicting. The impact of
      diabetes on neuromuscular function has been related to the co-existence of long
      term complications. Peripheral neuropathy has been shown to affect muscle by
      impairing motor nerve conduction. Also, vascular complications may contribute to
      the decline in muscle strength. However, muscle dysfunction occurs early in the
      course of diabetes and affects also the upper limbs, thus suggesting that it may
      develop independently of micro and macrovascular disease. A growing body of
      evidence indicates that hyperglycaemia may cause an alteration of the intrinsic
      properties of the muscle to generate force, via several mechanisms. Recently,
      resistance exercise has been shown to be an effective strategy to counteract the
      deterioration of muscular performance. High-intensity exercise seems to provide
      greater benefits than moderate-intensity training, whereas the effect of a power
      training is yet unknown. This article reviews the available literature on the
      impairment of muscle function induced by diabetes, the underlying mechanisms, and
      the effect of resistance training on this defect. Copyright (c) 2015 John Wiley &
      Sons, Ltd. 

PMID- 25950171
TI  - Biodegradable Microcarriers of Poly(Lactide-co-Glycolide) and Nano-Hydroxyapatite
      Decorated with IGF-1 via Polydopamine Coating for Enhancing Cell Proliferation
      and Osteogenic Differentiation.
AB  - In this study, insulin-like growth factor 1 (IGF-1) was successfully immobilized
      on the poly(lactide-co-glycolide)/hydroxyapatite (PLGA/HA) and pure PLGA
      microcarriers via polydopamine (pDA). The results demonstrated that the pDA layer
      facilitated simple and highly efficient immobilization of peptides on the
      microcarriers within 20 min. Mouse adipose-derived stem cells (ADSCs) attachment
      and proliferation on IGF-1-immobilized microcarriers were much higher than non
      immobilized ones. More importantly, the IGF-1-immobilized PLGA/HA microcarriers
      significantly increased alkaline phosphatase (ALP) activity and expression of
      osteogenesis-related genes of ADSCs. Therefore, it is considered that the IGF-1
      decorated PLGA/HA microcarriers will be of great value in the bone tissue
      engineering.

PMID- 25950172
TI  - Enhanced Performance of Community Health Service Centers during Medical Reforms
      in Pudong New District of Shanghai, China: A Longitudinal Survey.
AB  - BACKGROUND: The performance of community health service centers (CHSCs) has not
      been well monitored and analysed since China's latest community health reforms in
      2009. The aim of the current investigation was to evaluate the performing trends
      of the CHSCs and to analyze the main factors that could affect the performance in
      Pudong new district of Shanghai, China. METHODS: A regional performance
      assessment indicator system was applied to the evaluation of Pudong CHSCs'
      performance from 2011 to 2013. All of the data were sorted out by a panel, and
      analyzed using descriptive statistics and a generalized estimating equation
      model. RESULTS: We found that the overall performance increased annually, with a
      growing number of CHSCs achieving high scores. Significant differences were
      observed in institutional management, public health services, basic medical
      services and comprehensive satisfaction during the period of three years.
      However, we found no differences in the service scores of Chinese traditional
      medicine (CTM). The investigation also demonstrated that the key factors
      affecting performance were the location, information system level, family GP
      program and medical association program rather than the size of the center.
      However, the medical association participation appeared to have a significant
      negative effect on performance. CONCLUSIONS: It can be concluded from the three
      year investigation that the overall performance was improved, but that it could
      have been further enhanced, especially in institutional management and basic
      medical service; therefore, it is imperative that CHSCs undertake approaches such
      as optimizing the resource allocation and utilization, reinforcing the
      establishment of the information system level, extending the family GP program to
      more local communities, and promoting the medical association initiative.

PMID- 25950174
TI  - A reliability-based track fusion algorithm.
AB  - The common track fusion algorithms in multi-sensor systems have some defects,
      such as serious imbalances between accuracy and computational cost, the same
      treatment of all the sensor information regardless of their quality, high fusion
      errors at inflection points. To address these defects, a track fusion algorithm
      based on the reliability (TFR) is presented in multi-sensor and multi-target
      environments. To improve the information quality, outliers in the local tracks
      are eliminated at first. Then the reliability of local tracks is calculated, and
      the local tracks with high reliability are chosen for the state estimation
      fusion. In contrast to the existing methods, TFR reduces high fusion errors at
      the inflection points of system tracks, and obtains a high accuracy with less
      computational cost. Simulation results verify the effectiveness and the
      superiority of the algorithm in dense sensor environments. 

PMID- 25950173
TI  - Ciprofloxacin Derivatives Affect Parasite Cell Division and Increase the Survival
      of Mice Infected with Toxoplasma gondii.
AB  - Toxoplasmosis, caused by the protozoan Toxoplasma gondii, is a worldwide disease
      whose clinical manifestations include encephalitis and congenital malformations
      in newborns. Previously, we described the synthesis of new ethyl-ester
      derivatives of the antibiotic ciprofloxacin with ~40-fold increased activity
      against T. gondii in vitro, compared with the original compound. Cipro
      derivatives are expected to target the parasite's DNA gyrase complex in the
      apicoplast. The activity of these compounds in vivo, as well as their mode of
      action, remained thus far uncharacterized. Here, we examined the activity of the
      Cipro derivatives in vivo, in a model of acute murine toxoplasmosis. In addition,
      we investigated the cellular effects T. gondii tachyzoites in vitro, by
      immunofluorescence and transmission electron microscopy (TEM). When compared with
      Cipro treatment, 7-day treatments with Cipro derivatives increased mouse survival
      significantly, with 13-25% of mice surviving for up to 60 days post-infection
      (vs. complete lethality 10 days post-infection, with Cipro treatment). Light
      microscopy examination early (6 and 24h) post-infection revealed that 6-h
      treatments with Cipro derivatives inhibited the initial event of parasite cell
      division inside host cells, in an irreversible manner. By TEM and
      immunofluorescence, the main cellular effects observed after treatment with Cipro
      derivatives and Cipro were cell scission inhibition--with the appearance of
      'tethered' parasites--malformation of the inner membrane complex, and apicoplast
      enlargement and missegregation. Interestingly, tethered daughter cells resulting
      from Cipro derivatives, and also Cipro, treatment did not show MORN1 cap or
      centrocone localization. The biological activity of Cipro derivatives against C.
      parvum, an apicomplexan species that lacks the apicoplast, is, approximately, 50
      fold lower than that in T. gondii tachyzoites, supporting that these compounds
      targets the apicoplast. Our results show that Cipro derivatives improved the
      survival of mice acutely infected with T. gondii and inhibited parasite
      replication early in the first cycle of infection in vitro, highlighting their
      therapeutic potential for the treatment of toxoplasmosis.

PMID- 25950175
TI  - The philosophical approach: an interview with Ford Doolittle.

PMID- 25950177
TI  - Correction: Control, elimination, and eradication of river blindness: scenarios,
      timelines, and ivermectin treatment needs in Africa.

PMID- 25950176
TI  - Prognostic Significance of Combination of Preoperative Platelet Count and
      Neutrophil-Lymphocyte Ratio (COP-NLR) in Patients with Non-Small Cell Lung
      Cancer: Based on a Large Cohort Study.
AB  - INTRODUCTION: The aim of this study was to investigate the prognostic
      significance of the combination of the preoperative platelet count and neutrophil
      lymphocyte ratio (COP-NLR) for predicting postoperative survival of patients
      undergoing complete resection for non-small cell lung cancer (NSCLC). METHODS:
      The preoperative COP-NLR was calculated on the basis of data obtained.Patients
      with both an increased platelet count (>30.0 * 104 mm(-3)) and an elevated NLR
      (>2.3) were assigned a score of 2, and patients with one or neither were assigned
      as a score of 1 or 0, respectively. RESULTS: A total of 1238 NSCLC patients were
      enrolled in this analysis. Multivariate analysis using the 15 clinicolaboratory
      variables selected by univariate analyses demonstrated that the preoperative COP
      NLR was an independent prognostic factor for DFS (HR: 1.834, 95%CI: 1.536 to
      2.200, P<0.001) and OS (HR: 1.810, 95%CI: 1.587 to 2.056, P<0.001). In sub
      analyses by tumor stage (I, II, IIIA), a significant association was found
      between DFS and OS and level of COP-NLR in each subgroup (P<0.001, P=0.002,
      P<0.001 for DFS, respectively; P<0.001, P=0.001, P<0.001 for OS). When the
      subgroup of patients with high-risk COP-NLR (score of 2) was analyzed, no benefit
      of adjuvant chemotherapy could be found (P=0.237 for DFS and P=0.165 for OS).
      CONCLUSIONS: The preoperative COP-NLR is able to predict the prognosis of
      patients with NSCLC and divide these patients into three independent groups
      before surgery. Our results also demonstrate that high-risk patients based on the
      COP-NLR do not benefit from adjuvant chemotherapy. Independent validation of our
      findings is warranted.

PMID- 25950178
TI  - Assessment of Competition between Fisheries and Steller Sea Lions in Alaska Based
      on Estimated Prey Biomass, Fisheries Removals and Predator Foraging Behaviour.
AB  - A leading hypothesis to explain the dramatic decline of Steller sea lions
      (Eumetopias jubatus) in western Alaska during the latter part of the 20th century
      is a change in prey availability due to commercial fisheries. We tested this
      hypothesis by exploring the relationships between sea lion population trends,
      fishery catches, and the prey biomass accessible to sea lions around 33 rookeries
      between 2000 and 2008. We focused on three commercially important species that
      have dominated the sea lion diet during the population decline: walleye pollock,
      Pacific cod and Atka mackerel. We estimated available prey biomass by removing
      fishery catches from predicted prey biomass distributions in the Aleutian
      Islands, Bering Sea and Gulf of Alaska; and modelled the likelihood of sea lions
      foraging at different distances from rookeries (accessibility) using satellite
      telemetry locations of tracked animals. We combined this accessibility model with
      the prey distributions to estimate the prey biomass accessible to sea lions by
      rookery. For each rookery, we compared sea lion population change to accessible
      prey biomass. Of 304 comparisons, we found 3 statistically significant
      relationships, all suggesting that sea lion populations increased with increasing
      prey accessibility. Given that the majority of comparisons showed no significant
      effect, it seems unlikely that the availability of pollock, cod or Atka mackerel
      was limiting sea lion populations in the 2000s. 

PMID- 25950179
TI  - Coupled attitude-orbit dynamics and control for an electric sail in a
      heliocentric transfer mission.
AB  - The paper discusses the coupled attitude-orbit dynamics and control of an
      electric-sail-based spacecraft in a heliocentric transfer mission. The
      mathematical model characterizing the propulsive thrust is first described as a
      function of the orbital radius and the sail angle. Since the solar wind dynamic
      pressure acceleration is induced by the sail attitude, the orbital and attitude
      dynamics of electric sails are coupled, and are discussed together. Based on the
      coupled equations, the flight control is investigated, wherein the orbital
      control is studied in an optimal framework via a hybrid optimization method and
      the attitude controller is designed based on feedback linearization control. To
      verify the effectiveness of the proposed control strategy, a transfer problem
      from Earth to Mars is considered. The numerical results show that the proposed
      strategy can control the coupled system very well, and a small control torque can
      control both the attitude and orbit. The study in this paper will contribute to
      the theory study and application of electric sail. 

PMID- 25950180
TI  - Altered volume, morphology and composition of the pancreas in type 2 diabetes.
AB  - OBJECTIVE: Although impairment in pancreatic insulin secretion is known to
      precede the clinical diagnosis of type 2 diabetes by up to a decade, fasting
      blood glucose concentration only rises abnormally once the impairment reaches a
      critical threshold. Despite its centrality to the pathogenesis of type 2
      diabetes, the pancreas is the least studied organ due to its inaccessible
      anatomical position. Previous ultrasound and CT studies have suggested a possible
      decrease in pancreatic volume in type 2 diabetes. However, ultrasound techniques
      are relatively insensitive while CT uses ionizing radiation, making these
      modalities unsuitable for precise, longitudinal studies designed to explore the
      underlying mechanisms of type 2 diabetes. Hence there is a need to develop a non
      invasive, safe and precise method to quantitate pancreas volume. METHODS: We
      developed and applied magnetic resonance imaging at 3.0T to obtain balanced turbo
      field echo (BTFE) structural images of the pancreas, together with 3-point Dixon
      images to quantify pancreatic triglyceride content. Pancreas volume, morphology
      and triglyceride content was quantified in a group of 41 subjects with well
      controlled type 2 diabetes (HbA1c <= 7.6%) taking only metformin (duration of
      T2DM 5.7 +/- 0.7 years), and a control group of 14 normal glucose tolerance
      subjects matched for age, weight and sex. RESULTS: The mean pancreatic volume was
      found to be 33% less in type 2 diabetes than in normal glucose tolerant subjects
      (55.5 +/- 2.8 vs. 82.6 +/- 4.8 cm3; p < 0.0001). Pancreas volume was positively
      correlated with HOMA-beta in the type 2 diabetes subjects (r = 0.31; p = 0.03)
      and controls (r = 0.46; p = 0.05) considered separately; and in the whole
      population studied (r = 0.37; p = 0.003). In type 2 diabetes, the pancreas was
      typically involuted with a serrated border. Pancreatic triglyceride content was
      23% greater (5.4 +/- 0.3 vs. 4.4 +/- 0.4%; p = 0.02) in the type 2 diabetes
      group. CONCLUSION: This study describes for the first time gross abnormalities of
      the pancreas in early type 2 diabetes and quantifies the decrease in pancreas
      size, the irregular morphology and increase in fat content.

PMID- 25950181
TI  - Detecting the influence of spreading in social networks with excitable sensor
      networks.
AB  - Detecting spreading outbreaks in social networks with sensors is of great
      significance in applications. Inspired by the formation mechanism of humans'
      physical sensations to external stimuli, we propose a new method to detect the
      influence of spreading by constructing excitable sensor networks. Exploiting the
      amplifying effect of excitable sensor networks, our method can better detect
      small-scale spreading processes. At the same time, it can also distinguish large
      scale diffusion instances due to the self-inhibition effect of excitable
      elements. Through simulations of diverse spreading dynamics on typical real-world
      social networks (Facebook, coauthor, and email social networks), we find that the
      excitable sensor networks are capable of detecting and ranking spreading
      processes in a much wider range of influence than other commonly used sensor
      placement methods, such as random, targeted, acquaintance and distance
      strategies. In addition, we validate the efficacy of our method with diffusion
      data from a real-world online social system, Twitter. We find that our method can
      detect more spreading topics in practice. Our approach provides a new direction
      in spreading detection and should be useful for designing effective detection
      methods. 

PMID- 25950182
TI  - Limited Contribution of IL-36 versus IL-1 and TNF Pathways in Host Response to
      Mycobacterial Infection.
AB  - IL-36 cytokines are members of the IL-1 family of cytokines that stimulate
      dendritic cells and T cells leading to enhanced T helper 1 responses in vitro and
      in vivo; however, their role in host defense has not been fully addressed thus
      far. The objective of this study was to examine the role of IL-36R signaling in
      the control of mycobacterial infection, using models of systemic attenuated M.
      bovis BCG infection and virulent aerogenic M. tuberculosis infection. IL-36gamma
      expression was increased in the lung of M. bovis BCG infected mice. However, IL
      36R deficient mice infected with M. bovis BCG showed similar survival and control
      of the infection as compared to wild-type mice, although their lung pathology and
      CXCL1 response were transiently different. While highly susceptible TNF-alpha
      deficient mice succumbed with overwhelming M. tuberculosis infection, and IL-1RI
      deficient mice showed intermediate susceptibility, IL-36R-deficient mice
      controlled the infection, with bacterial burden, lung inflammation and pathology,
      similar to wild-type controls. Therefore, IL-36R signaling has only limited
      influence in the control of mycobacterial infection. 

PMID- 25950183
TI  - Random versus Game Trail-Based Camera Trap Placement Strategy for Monitoring
      Terrestrial Mammal Communities.
AB  - Camera trap surveys exclusively targeting features of the landscape that increase
      the probability of photographing one or several focal species are commonly used
      to draw inferences on the richness, composition and structure of entire mammal
      communities. However, these studies ignore expected biases in species detection
      arising from sampling only a limited set of potential habitat features. In this
      study, we test the influence of camera trap placement strategy on community-level
      inferences by carrying out two spatially and temporally concurrent surveys of
      medium to large terrestrial mammal species within Tanzania's Ruaha National Park,
      employing either strictly game trail-based or strictly random camera placements.
      We compared the richness, composition and structure of the two observed
      communities, and evaluated what makes a species significantly more likely to be
      caught at trail placements. Observed communities differed marginally in their
      richness and composition, although differences were more noticeable during the
      wet season and for low levels of sampling effort. Lognormal models provided the
      best fit to rank abundance distributions describing the structure of all observed
      communities, regardless of survey type or season. Despite this, carnivore species
      were more likely to be detected at trail placements relative to random ones
      during the dry season, as were larger bodied species during the wet season. Our
      findings suggest that, given adequate sampling effort (> 1400 camera trap
      nights), placement strategy is unlikely to affect inferences made at the
      community level. However, surveys should consider more carefully their choice of
      placement strategy when targeting specific taxonomic or trophic groups. 

PMID- 25950184
TI  - Correction: CD169-Mediated Trafficking of HIV to Plasma Membrane Invaginations in
      Dendritic Cells Attenuates Efficacy of Anti-gp120 Broadly Neutralizing
      Antibodies.

PMID- 25950185
TI  - Comprehensive stroke centers may be associated with improved survival in
      hemorrhagic stroke.
AB  - BACKGROUND: Comprehensive stroke centers (CSCs) provide a full spectrum of
      neurological and neurosurgical services to treat complex stroke patients. CSCs
      have been shown to improve clinical outcomes and mitigate disparities in ischemic
      stroke patients. It is believed that CSCs also improve outcomes in hemorrhagic
      stroke. METHODS AND RESULTS: We used the Myocardial Infarction Data Acquisition
      System (MIDAS) database, which includes data on patients discharged with a
      primary diagnosis of intracerebral hemorrhage (ICH; International Classification
      of Diseases, Ninth Revision [ICD-9] 431) and subarachnoid hemorrhage (SAH; ICD-9
      430) from all nonfederal acute care hospitals in New Jersey (NJ) between 1996 and
      2012. Out-of-hospital deaths were assessed by matching MIDAS records with NJ
      death registration files. The primary outcome variable was 90-day all-cause
      mortality. The primary independent variable was CSC versus primary stroke center
      (PSC) and nonstroke center (NSC) admission. Multivariate logistic models were
      used to measure the effects of available covariates. Overall, 36 981 patients
      were admitted with a primary diagnosis of ICH or SAH during the study period, of
      which 40% were admitted to a CSC. Patients admitted to CSCs were more likely to
      have neurosurgical or endovascular interventions than those admitted to a PSC/NSC
      (18.9% vs. 4.7%; P<0.0001). CSC admission was associated with lower adjusted 90
      day mortality (35.0% vs. 40.3%; odds ratio, 0.93; 95% confidence interval, 0.89
      to 0.97) for hemorrhagic stroke. This was particularly true for those admitted
      with SAH. CONCLUSIONS: Hemorrhagic stroke patients admitted to CSCs are more
      likely to receive neurosurgical and endovascular treatments and be alive at 90
      days than patients admitted to other hospitals.

PMID- 25950186
TI  - Visualization and functional dissection of coaxial paired SpoIIIE channels across
      the sporulation septum.
AB  - SpoIIIE is a membrane-anchored DNA translocase that localizes to the septal
      midpoint to mediate chromosome translocation and membrane fission during Bacillus
      subtilis sporulation. Here we use cell-specific protein degradation and
      quantitative photoactivated localization microscopy in strains with a thick
      sporulation septum to investigate the architecture and function of the SpoIIIE
      DNA translocation complex in vivo. We were able to visualize SpoIIIE complexes
      with approximately equal numbers of molecules in the mother cell and the
      forespore. Cell-specific protein degradation showed that only the mother cell
      complex is required to translocate DNA into the forespore, whereas degradation in
      either cell reverses membrane fission. Our data suggest that SpoIIIE assembles a
      coaxially paired channel for each chromosome arm comprised of one hexamer in each
      cell to maintain membrane fission during DNA translocation. We show that SpoIIIE
      can operate, in principle, as a bi-directional motor that exports DNA. 

PMID- 25950187
TI  - Changing Gender Norms and Reducing HIV and Violence Risk Among Workers and
      Students in China.
AB  - Global evidence demonstrates that inequitable gender norms negatively influence
      key health outcomes (e.g., violence, HIV/STI), and the importance of male
      involvement in prevention efforts. The China Family Planning Association and PATH
      partnered to develop and evaluate a gender-focused behavior change communication
      intervention for HIV and violence prevention. Eight participatory education
      sessions-adapted for the Chinese setting-were implemented in factories and
      schools. Baseline and endline surveys with participants (219 male factory workers
      and 496 male vocational students) were conducted. Support for (in)equitable norms
      was measured by the Gender Equitable Men Scale, as well as partner violence and
      communication. Focus groups with male and female workers/students, teachers, and
      factory managers were used to corroborate findings. At baseline, many workers and
      students supported inequitable gender norms, with workers generally being more
      inequitable. At endline, significant positive changes in gender-related views
      (e.g., reduction from 42% to 18% of workers agreeing that "a woman should
      tolerate violence in order to keep her family together") and behaviors (e.g.,
      reduction from 15% to 7% of students reporting partner violence over the past 3
      months) were reported. Results suggest that a relatively low intensity
      intervention can influence important gender norms and related behaviors. 

PMID- 25950188
TI  - Intensity-modulated radiation therapy with simultaneous integrated boost combined
      with concurrent chemotherapy for the treatment of anal cancer patients: 4-year
      results of a consecutive case series.
AB  - PURPOSE: To report the 4-year outcomes of a consecutive series of anal cancer
      patients treated with concurrent chemo-radiation delivered with intensity
      modulated radiotherapy (IMRT), employing a simultaneous integrated boost (SIB)
      approach. METHODS: A consecutive series of 54 patients was enrolled between 2007
      and 2013. Treatment schedule consisted of 50.4 Gy/28 fractions (1.8 Gy daily) to
      the gross tumor volume, while the elective nodal volumes were prescribed 42 Gy/28
      fractions (1.5 Gy/daily) for patients having a cT2N0 disease. Patients with cT3
      T4/N0-N3 tumors were prescribed 54 (T3) or 60 (T4) Gy/30 fractions (1.8-2 Gy
      daily) to the gross tumor volume; gross nodal volumes were prescribed 50.4 Gy/30
      fr (1.68 Gy daily) if sized <= 3 cm or 54 Gy/30 fr (1.8 Gy daily) if > 3 cm;
      elective nodal regions were given 45 Gy/30 fractions (1.5 Gy daily). Chemotherapy
      was administered concurrently according to the Nigro's regimen. Primary endpoint
      was colostomy-free survival (CFS). Secondary endpoints were local control (LC),
      disease-free survival (DFS), cancer-specific survival (CSS), overall survival
      (OS), and toxicity profile. RESULTS: Median follow up was 32.6 months (range 12
      84). The actuarial probability of being alive at 4 years without a colostomy
      (CFS) was 68.9% (95% CI: 50.3%-84.7%). Actuarial 4-year OS, CSS, DFS, and LC were
      77.7% (95% CI: 60.7-88.1%), 81.5% (95% CI: 64%-91%), 65.5% (95% CI: 47.7%-78.5%),
      and 84.6% (95% CI: 71.6%-92%). Actuarial 4-year metastasis-free survival was
      74.4% (95% CI: 55.5%-86.2%). Maximum detected acute toxicities were as follows:
      dermatologic -G3: 13%; GI-G3: 8%; GU-G3: 2%; anemia-G3: 2%; neutropenia-G3:11%;
      G4: 2%; thrombocytopenia- G3:2%. Four-year G2 chronic toxicity rates were 2.5%
      (95% CI: 3.6-16.4) for GU, 14.4% (95% CI: 7.1-28) for GI, 3.9% (95% CI: 1%-14.5%)
      for skin, and 4.2% (95% CI: 1.1-15.9) for genitalia. CONCLUSIONS: Our study shows
      the feasibility of IMRT in the combined modality treatment of anal cancer, with
      comparable results to the literature with respect to LC, sphincter preservation
      and survival. Acute toxicity is lower if compared to series employing standard
      techniques. Our results support the use of IMRT on a routine basis for the
      treatment of anal cancer.

PMID- 25950189
TI  - Effects of stabilization and sludge properties in a combined process of anaerobic
      digestion and thermophilic aerobic digestion.
AB  - A novel process of combining mesophilic (<35 degrees C) anaerobic digestion with
      the thermophilic (55 degrees C) aerobic digestion process (AN-TAD) was designed
      to stabilize sludge and economize aeration energy. Effects of stabilization and
      sludge properties for AN-TAD process were evaluated by batch experiments during a
      25 d digestion period. The sludges digested by AN-TAD process achieved the
      requirements for Class-A sludge standard. The sludge at total solid (TS) 5.4% had
      the highest value of decay coefficient K(d(55)) at 0.1851 d(-1) among the three
      TS contents according to the first-order kinetics equation. Oxidation reduction
      potential at below 0 mV remained for sludges at TSs of 6.5%, 5.4%, and 4.6% for
      at least 15 d because of initial hydrolytic-acidification. Concentrations of
      nitrogen and phosphorus in sludges at TSs of 6.5%, 5.4%, and 4.6% gradually
      increased up to the highest values in the supernatant during the initial 13 d,
      causing low utilized value in land application as a fertilizer. Prolonging the
      retention time for more than 15 d was considered because soluble phosphorus
      precipitated in the solid phase. High content of soluble organic matters of the
      soluble chemical oxygen demand, protein, and polysaccharide in the supernatant
      caused deterioration in sludge dewaterability rates.

PMID- 25950190
TI  - Eradication of T315I mutation in chronic myeloid leukemia without third
      generation tyrosine kinase inhibitor: a case report.
AB  - We report the case of a patient bearing a T315I-mutant chronic myeloid leukemia
      resistant to nilotinib, successfully treated with omacetaxine and then with
      dasatinib. After 9 months of nilotinib, the patient achieved a major molecular
      response but relapsed 3 months later due to the T315I mutation. Because third
      generation tyrosine kinase inhibitor was not available and the patient refused
      bone marrow transplantation, he received two cycles of omacetaxine. This
      treatment had been stopped after two cycles because of clinical intolerance, but
      a major molecular response and total disappearance of the T315I clone was
      obtained. Treatment with dasatinib was then started and after 34-month follow-up
      the patient is still in major molecular response, thus suggesting that
      eradication of the T315I mutation could be achieved without third-generation
      tyrosine kinase inhibitors. 

PMID- 25950191
TI  - Time-dependent quantum transport through an interacting quantum dot beyond
      sequential tunneling: second-order quantum rate equations.
AB  - A general theoretical formulation for the effect of a strong on-site Coulomb
      interaction on the time-dependent electron transport through a quantum dot under
      the influence of arbitrary time-varying bias voltages and/or external fields is
      presented, based on slave bosons and the Keldysh nonequilibrium Green's function
      (GF) techniques. To avoid the difficulties of computing double-time GFs, we
      generalize the propagation scheme recently developed by Croy and Saalmann to
      combine the auxiliary-mode expansion with the celebrated Lacroix's decoupling
      approximation in dealing with the second-order correlated GFs and then establish
      a closed set of coupled equations of motion, called second-order quantum rate
      equations (SOQREs), for an exact description of transient dynamics of electron
      correlated tunneling. We verify that the stationary solution of our SOQREs is
      able to correctly describe the Kondo effect on a qualitative level. Moreover, a
      comparison with other methods, such as the second-order von Neumann approach and
      Hubbard-I approximation, is performed. As illustrations, we investigate the
      transient current behaviors in response to a step voltage pulse and a harmonic
      driving voltage, and linear admittance as well, in the cotunneling regime. 

PMID- 25950193
TI  - Cost-effectiveness of saxagliptin vs glimepiride as a second-line therapy added
      to metformin in Type 2 diabetes in China.
AB  - OBJECTIVE: This study aims to estimate the long-term cost-effectiveness of
      saxagliptin + metformin (SAXA + MET) vs glimepiride + metformin (GLI + MET) in
      patients with Type 2 diabetes mellitus (T2DM) inadequately controlled with MET in
      China. METHODS: The Cardiff Model was used to simulate disease progression and
      estimate the long-term effect of treatments on patients. Systematic literature
      reviews and hospital surveys were conducted to obtain patients profiles, clinical
      data, and costs. Health insurance costs (2014Y) were estimated over a 40-year
      period. One-way and probabilistic sensitivity analyses were performed. RESULTS:
      SAXA + MET had lower predicted incidences of cardiovascular and hypoglycemia
      events and a decreased total cost compared with GLI + MET (Y241,072,807 vs
      Y285,455,177). There were increased numbers of quality-adjusted life-years
      (QALYs; 1.01/patient) and life-years (Lys; 0.03/patient) gained with SAXA + MET
      compared with GLI + MET, and the incremental cost of SAXA + MET vs GLI + MET (
      Y44,382) resulted in -Y43,883/QALY and -Y1,710,926/LY gained with SAXA + MET.
      Sensitivity analyses confirmed that the results were robust. CONCLUSION: In
      patients with T2DM in China, SAXA + MET was more cost-effective and was well
      tolerated with fewer adverse effects (AEs) compared with GLI + MET. As a second
      line therapy for T2DM, SAXA may address some of the unmet medical needs
      attributable to AEs in the treatment of T2DM.

PMID- 25950194
TI  - Fluorene and Phenanthrene Uptake and Accumulation by Wheat, Alfalfa and Sunflower
      from the Contaminated Soil.
AB  - Polycyclic Aromatic Hydrocarbons (PAHs) are diverse organic contaminants released
      into the environment by both natural and anthropogenic activities. These
      compounds have negative impacts on plants growth and development. Although there
      are many reports on their existence in different parts of plant, their uptake and
      translocation pathways and mechanisms are not well understood yet. This paper
      highlights the uptake, translocation and accumulation of PAHs by wheat, sunflower
      and alfalfa through an experimental study under controlled conditions. Seeds were
      cultivated in a soil containing 50 mg/kg of phenanthrene and fluorene and their
      concentrations in plants roots and shoots were determined using a gas
      chromatograph after 7 and 14 days. The results showed that phenanthrene and
      fluorene concentrations in the treated plants were increased over the time. PAHs
      bioavailability was time and species dependent and generally, phenanthrene uptake
      and translocation was faster than that of fluorene, probably due to their higher
      Kow. Fluorene tended to accumulate in roots, but phenanthrene was transported to
      aerial parts of plants. 

PMID- 25950192
TI  - Molecular mechanism of statin-mediated LOX-1 inhibition.
AB  - Statins are largely used in clinics in the treatment of patients with
      cardiovascular diseases for their effect on lowering circulating cholesterol.
      Lectin-like oxidized low-density lipoprotein (LOX-1), the primary receptor for ox
      LDL, plays a central role in the pathogenesis of atherosclerosis and
      cardiovascular disorders. We have recently shown that chronic exposure of cells
      to lovastatin disrupts LOX-1 receptor cluster distribution in plasma membranes,
      leading to a marked loss of LOX-1 function. Here we investigated the molecular
      mechanism of statin-mediated LOX-1 inhibition and we demonstrate that all tested
      statins are able to displace the binding of fluorescent ox-LDL to LOX-1 by a
      direct interaction with LOX-1 receptors in a cell-based binding assay. Molecular
      docking simulations confirm the interaction and indicate that statins completely
      fill the hydrophobic tunnel that crosses the C-type lectin-like (CTLD)
      recognition domain of LOX-1. Classical molecular dynamics simulation technique
      applied to the LOX-1 CTLD, considered in the entire receptor structure with or
      without a statin ligand inside the tunnel, indicates that the presence of a
      ligand largely increases the dimer stability. Electrophoretic separation and
      western blot confirm that different statins binding stabilize the dimer assembly
      of LOX-1 receptors in vivo. The simulative and experimental results allow us to
      propose a CTLD clamp motion, which enables the receptor-substrate coupling. These
      findings reveal a novel and significant functional effect of statins. 

PMID- 25950195
TI  - A combination of PhP typing and beta-d-glucuronidase gene sequence variation
      analysis for differentiation of Escherichia coli from humans and animals.
AB  - We investigated the usefulness of the beta-d-glucuronidase gene variance in
      Escherichia coli as a microbial source tracking tool using a novel algorithm for
      comparison of sequences from a prescreened set of host-specific isolates using a
      high-resolution PhP typing method. A total of 65 common biochemical phenotypes
      belonging to 318 E. coli strains isolated from humans and domestic and wild
      animals were analysed for nucleotide variations at 10 loci along a 518 bp
      fragment of the 1812 bp beta-d-glucuronidase gene. Neighbour-joining analysis of
      loci variations revealed 86 (76.8%) human isolates and 91.2% of animal isolates
      were correctly identified. Pairwise hierarchical clustering improved assignment;
      where 92 (82.1%) human and 204 (99%) animal strains were assigned to their
      respective cluster. Our data show that initial typing of isolates and selection
      of common types from different hosts prior to analysis of the beta-d
      glucuronidase gene sequence improves source identification. We also concluded
      that numerical profiling of the nucleotide variations can be used as a valuable
      approach to differentiate human from animal E. coli. This study signifies the
      usefulness of the beta-d-glucuronidase gene as a marker for differentiating human
      faecal pollution from animal sources. 

PMID- 25950196
TI  - Discovering novel carbonic anhydrase type IX (CA IX) inhibitors from seven
      million compounds using virtual screening and in vitro analysis.
AB  - Carbonic anhydrase type IX (CA IX) enzyme is mostly over expressed in different
      cancer cell lines and tumor tissues. Potent CA IX inhibitors can be effective for
      adjusting the pH imbalance in tumor cells. In the present work, we represented
      the successful application of high throughput virtual screening (HTVS) of large
      dataset from ZINC database included of ~7 million compounds to discover novel
      inhibitors of CA IX. HTVS and molecular docking were performed using consequence
      Glide/standard precision (SP), extra precision (XP) and induced fit docking (IFD)
      molecular docking protocols. For each compound, docking code calculates a set of
      low-energy poses and then exhaustively scans the binding pocket of the target
      with small compounds. Novel CA IX inhibitor candidates were suggested based on
      molecular modeling studies and a few of them were tested using in vitro analysis.
      These compounds were determined as good inhibitors against human CA IX target
      with Ki in the range of 0.85-1.58 MUM. In order to predict the pharmaceutical
      properties of the selected compounds, ADME (absorption, distribution, metabolism
      and excretion) analysis was also carried out.

PMID- 25950197
TI  - Hybrid germanium iodide perovskite semiconductors: active lone pairs, structural
      distortions, direct and indirect energy gaps, and strong nonlinear optical
      properties.
AB  - The synthesis and properties of the hybrid organic/inorganic germanium perovskite
      compounds, AGeI3, are reported (A = Cs, organic cation). The systematic study of
      this reaction system led to the isolation of 6 new hybrid semiconductors. Using
      CsGeI3 (1) as the prototype compound, we have prepared methylammonium, CH3NH3GeI3
      (2), formamidinium, HC(NH2)2GeI3 (3), acetamidinium, CH3C(NH2)2GeI3 (4),
      guanidinium, C(NH2)3GeI3 (5), trimethylammonium, (CH3)3NHGeI3 (6), and
      isopropylammonium, (CH3)2C(H)NH3GeI3 (7) analogues. The crystal structures of the
      compounds are classified based on their dimensionality with 1-4 forming 3D
      perovskite frameworks and 5-7 1D infinite chains. Compounds 1-7, with the
      exception of compounds 5 (centrosymmetric) and 7 (nonpolar acentric), crystallize
      in polar space groups. The 3D compounds have direct band gaps of 1.6 eV (1), 1.9
      eV (2), 2.2 eV (3), and 2.5 eV (4), while the 1D compounds have indirect band
      gaps of 2.7 eV (5), 2.5 eV (6), and 2.8 eV (7). Herein, we report on the second
      harmonic generation (SHG) properties of the compounds, which display remarkably
      strong, type I phase-matchable SHG response with high laser-induced damage
      thresholds (up to ~3 GW/cm(2)). The second-order nonlinear susceptibility,
      chiS(2), was determined to be 125.3 +/- 10.5 pm/V (1), (161.0 +/- 14.5) pm/V (2),
      143.0 +/- 13.5 pm/V (3), and 57.2 +/- 5.5 pm/V (4). First-principles density
      functional theory electronic structure calculations indicate that the large SHG
      response is attributed to the high density of states in the valence band due to
      sp-hybridization of the Ge and I orbitals, a consequence of the lone pair
      activation.

PMID- 25950198
TI  - Analysis of pulmonary surfactant in rat lungs after inhalation of nanomaterials:
      Fullerenes, nickel oxide and multi-walled carbon nanotubes.
AB  - The health risks of inhalation exposure to engineered nanomaterials in the
      workplace are a major concern in recent years, and hazard assessments of these
      materials are being conducted. The pulmonary surfactant of lung alveoli is the
      first biological entity to have contact with airborne nanomaterials in inhaled
      air. In this study, we retrospectively evaluated the pulmonary surfactant
      components of rat lungs after a 4-week inhalation exposure to three different
      nanomaterials: fullerenes, nickel oxide (NiO) nanoparticles and multi-walled
      carbon nanotubes (MWCNT), with similar levels of average aerosol concentration
      (0.13-0.37 mg/m(3)). Bronchoalveolar lavage fluid (BALF) of the rat lungs stored
      after previous inhalation studies was analyzed, focusing on total protein and the
      surfactant components, such as phospholipids and surfactant-specific SP-D
      (surfactant protein D) and the BALF surface tension, which is affected by SP-B
      and SP-C. Compared with a control group, significant changes in the BALF surface
      tension and the concentrations of phospholipids, total protein and SP-D were
      observed in rats exposed to NiO nanoparticles, but not in those exposed to
      fullerenes. Surface tension and the levels of surfactant phospholipids and
      proteins were also significantly different in rats exposed to MWCNTs. The
      concentrations of phospholipids, total protein and SP-D and BALF surface tension
      were correlated significantly with the polymorphonuclear neutrophil counts in the
      BALF. These results suggest that pulmonary surfactant components can be used as
      measures of lung inflammation.

PMID- 25950199
TI  - Novel Anisotropic Magnetoelectric Effect on delta-FeO(OH)/P(VDF-TrFE)
      Multiferroic Composites.
AB  - The past decade has witnessed increased research effort on multiphase
      magnetoelectric (ME) composites. In this scope, this paper presents the
      application of novel materials for the development of anisotropic magnetoelectric
      sensors based on delta-FeO(OH)/P(VDF-TrFE) composites. The composite is able to
      precisely determine the amplitude and direction of the magnetic field. A new ME
      effect is reported in this study, as it emerges from the magnetic rotation of the
      delta-FeO(OH) nanosheets inside the piezoelectric P(VDF-TrFE) polymer matrix.
      delta-FeO(OH)/P(VDF-TrFE) composites with 1, 5, 10, and 20 delta-FeO(OH) filler
      weight percentage in three delta-FeO(OH) alignment states (random, transversal,
      and longitudinal) have been developed. Results have shown that the modulus of the
      piezoelectric response (10-24 pC.N(-1)) is stable at least up to three months,
      the shape and magnetization maximum value (3 emu.g(-1)) is dependent on delta
      FeO(OH) content, and the obtained ME voltage coefficient, with a maximum of ~0.4
      mV.cm(-1).Oe(-1), is dependent on the incident magnetic field direction and
      intensity. In this way, the produced materials are suitable for innovative
      anisotropic sensor and actuator applications. 

PMID- 25950200
TI  - Improving the Visible Light Photoactivity of Supported Fullerene Photocatalysts
      through the Use of [C70] Fullerene.
AB  - We herein present the first instance of employing [C70] fullerene for
      photocatalytic 1O2 production in water, through covalent immobilization onto a
      mesoporous silica support via nucelophilic amine addition directly to fullerene's
      cage. This attachment approach prevents the aggregation of individual fullerene
      molecules in water, thus allowing fullerene to retain its photoactivity, yet is
      much less complex than other techniques commonly pursued to create such supported
      fullerene materials, which typically rely on water-soluble fullerene derivatives
      and elaborate immobilization methods. The solid-supported C70 material exhibits
      significantly improved aqueous visible-light photoactivity compared to previous
      C60- and C60-derivative-based supported fullerene materials. Further, this
      material rapidly inactivates MS2 bacteriophage under sunlight illumination,
      oxidizes various organic contaminants, and does not appear to be significantly
      fouled by natural organic matter (NOM), highlighting the potential of these
      materials in real-world applications. Collectively, the ease of preparation and
      significantly enhanced visible-light photoactivity of these materials advance
      fullerene-based technologies for water treatment.

PMID- 25950201
TI  - Gambierone, a Ladder-Shaped Polyether from the Dinoflagellate Gambierdiscus
      belizeanus.
AB  - A new natural product named gambierone (1) was isolated from the cultured
      dinoflagellate Gambierdiscus belizeanus. The structure of this compound features
      an unprecedented polyether skeleton and an unusual right-hand side chain. Its
      relative configuration was fully determined by interpretation of ROESY experiment
      and comparison between experimental and theoretical NMR data. Although the
      succession of cycles has no chemical similarity with ciguatoxins, 1 has a
      molecular formula and biological activity similar to those of CTX-3C, although
      much lower in intensity. 

PMID- 25950202
TI  - Quaternary ammonium groups exposed at the surface of silica nanoparticles
      suitable for DNA complexation in the presence of cationic lipids.
AB  - The production of silica nanoparticles (NPs) exposing quaternary ammonium groups
      (NPQ(+)) has been achieved using an optimized chemical surface functionalization
      protocol. The procedures of surface modification and quaternization of amino
      groups were validated by diffuse reflectance infrared Fourier transform (DRIFT)
      and (1)H NMR spectroscopies. Compared to nonquaternized aminated NP, the
      colloidal stability of NPQ(+) was improved for various pH and salt conditions as
      assessed by zeta potential and light scattering measurements. In the context of
      their use for nucleic acid delivery, DNA efficiently bound to NPQ(+) analyzed by
      cosedimentation assays for a large pH range and various NaCl concentrations and
      exhibited a better efficacy at basic pH than nonquaternized NP. The study of
      NPQ(+)/DNA/cationic lipids ternary complexes was carried out with 1,2-dioleoyl-3
      trimethylammonium propane (DOTAP) and analyzed by cryo-electron microscopy (cryo
      EM). Cryo-EM images showed ternary assemblies where condensed DNA strands are
      sandwiched between the NPQ(+) surface and the cationic lipid bilayer. Because of
      an unusual electrostatic colloidal stability of NPQ(+) and a high propensity to
      bind DNA molecules particularly at high salt concentrations, a novel type of
      ternary assembly has been formed that might impact the delivery properties of
      these complexes including their stability in biological environment. 

PMID- 25950203
TI  - Dissociative Photoionization of He...Li2: A Theoretical Study.
AB  - Dissociative photoionization of the He...Li2 van der Waals complex to the ground
      electronic state of the He...Li2+ ion is investigated theoretically. The
      photoionization cross section is computed using existing interaction potentials.
      Resonances are found on top of a structured continuum. They are assigned to
      vibrational predissociation of the ion by comparison with Fermi Golden Rule
      calculations. Because of the differences in potential energy surfaces between the
      neutral and ionic complexes, only the resonances corresponding to quasibound
      states with the highest excitation in the van der Waals modes are visible. The
      other quasi bound states obtained in the Fermi Golden Rule calculations can give
      information on vibrational energy relaxation rates in other collisional processes
      involving the lithium dimer ion and a helium atom.

PMID- 25950204
TI  - Airway IL-1beta and Systemic Inflammation as Predictors of Future Exacerbation
      Risk in Asthma and COPD.
AB  - BACKGROUND: The innate inflammatory pathways involved in the frequent exacerbator
      phenotypes of asthma and COPD are not well understood. This study aimed to
      investigate airway innate immune activation and systemic inflammation as
      predictors of exacerbations in asthma and COPD. METHODS: In this prospective
      cohort study, baseline airway IL-1beta, serum C-reactive protein, and IL-6 were
      assessed in 152 participants with stable asthma (n = 63) or COPD (n = 89) and
      were related to exacerbations over the following 12 months. Clinical
      characteristics and inflammatory biomarkers were compared between the frequent
      (two or more exacerbations in the follow-up) and infrequent exacerbators. The
      frequent exacerbation phenotype and exacerbation frequency were analyzed with
      multivariable modeling. The relationships among airway inflammation, systemic
      inflammation, and future exacerbations were examined using path analysis.
      RESULTS: Ninety-four participants experienced a total of 201 exacerbations, and
      36.4% had two or more exacerbations. Serum IL-6 and sputum gene expression of IL
      1beta at baseline were higher in the frequent exacerbators with COPD. Significant
      pathways initiated by previous exacerbations were identified as occurring through
      activation of the IL-1beta-systemic inflammatory axis leading to future
      exacerbations in COPD. Systemic inflammation was also associated with increased
      exacerbation risk in asthma. CONCLUSIONS: Airway IL-1beta and systemic
      inflammation are associated with frequent exacerbations and may mediate a vicious
      cycle between previous and future exacerbations in COPD. Treatment strategies
      aimed at attenuating these inflammatory pathways to reduce COPD exacerbations
      deserve further investigation.

PMID- 25950205
TI  - Brief Report: HIV Testing Among Pregnant Women Who Attend Antenatal Care in
      Malawi.
AB  - Malawi adopted the Option B+ strategy in 2011. Its success in reducing mother-to
      child transmission depends on coverage and timing of HIV testing. We assessed HIV
      status ascertainment and its predictors during pregnancy. HIV status
      ascertainment was 82.3% (95% confidence interval: 80.2 to 85.9) in the pre-Option
      B+ period and 85.7% (95% confidence interval: 83.4 to 88.0) in the Option B+
      period. Higher HIV ascertainment was independently associated with higher age,
      attending antenatal care more than once, and registration in 2010. The observed
      high variability of HIV ascertainment between sites (50.6%-97.7%) and over time
      suggests that HIV test kit shortages and insufficient numbers of staff posed
      major barriers to reducing mother-to-child transmission. 

PMID- 25950206
TI  - Pharmacokinetics of Once Versus Twice Daily Darunavir in Pregnant HIV-Infected
      Women.
AB  - OBJECTIVE: To describe darunavir (DRV) pharmacokinetics with once-and twice-daily
      dosing during pregnancy and postpartum in HIV-infected women. DESIGN: Women were
      enrolled in International Maternal Pediatric Adolescent AIDS Clinical Trials
      Network Protocol P1026s, a prospective nonblinded study of antiretroviral
      pharmacokinetics in HIV-infected pregnant women that included separate cohorts
      receiving DRV/ritonavir dosed at either 800 mg/100 mg once daily or 600 mg/100 mg
      twice daily. METHODS: Intensive steady-state 12- or 24-hour pharmacokinetic
      profiles were performed during the second trimester, third trimester, and
      postpartum. DRV was measured using high-performance liquid chromatography
      (detection limit: 0.09 MUg/mL). RESULTS: Pharmacokinetic data were available for
      64 women (30 once daily and 34 twice daily dosing). Median DRV area under the
      concentration-time curve (AUC) and maximum concentration were significantly
      reduced during pregnancy with both dosing regimens compared with postpartum,
      whereas the last measurable concentration (Clast) was also reduced during
      pregnancy with once daily DRV. DRV AUC with once daily dosing was reduced by 38%
      during the second trimester and by 39% during the third trimester. With twice
      daily dosing, DRV AUC was reduced by 26% in both trimesters. The median (range)
      ratio of cord blood/maternal delivery DRV concentration in 32 paired samples was
      0.18 (range: 0-0.82). CONCLUSIONS: DRV exposure is reduced by pregnancy. To
      achieve DRV plasma concentrations during pregnancy equivalent to those seen in
      nonpregnant adults, an increased twice daily dose may be necessary. This may be
      especially important for treatment-experienced women who may have developed
      antiretroviral resistance mutations.

PMID- 25950207
TI  - HIV and Sexually Transmitted Infection Incidence and Associated Risk Factors
      Among High-Risk MSM and Male-to-Female Transgender Women in Lima, Peru.
AB  - BACKGROUND: Men who have sex with men (MSM) and male-to-female transgender women
      (TW) are at increased risk of HIV and sexually transmitted infections (STIs). We
      evaluated factors associated with incidence of HIV, HSV-2, and chlamydia and
      gonorrhea (anal and pharyngeal). METHODS: We used data from the Comunidades
      Positivas trial with MSM/TW who have sex with men in Lima, Peru. Participants
      were asked about sexual risk behaviors and underwent HIV/STI testing at baseline
      and 9- and 18-month follow-ups. We used discrete time proportional hazards
      regression to calculate hazard ratios for variables associated with incidence of
      each STI. RESULTS: Among 718 MSM/TW, HIV incidence was 3.6 cases per 100 person
      years. HIV incidence was associated with having an incident STI adjusted hazard
      ratio (aHR) of 3.73. Unprotected receptive anal intercourse was associated with
      incident anal chlamydia (aHR 2.20). An increased number of sexual partners
      increased incident HSV-2 (aHR 3.15 for 6-14 partners and 3.97 for 15-46 partners
      compared with 0-2 partners). The risk of anal gonorrhea decreased with each
      sexually active year (aHR 0.94) and increased for unprotected compensated sex
      (aHR 2.36). The risk of pharyngeal gonorrhea also decreased with each year since
      sexual debut (aHR 0.95). The risk of anal chlamydia decreased with each sexually
      active year (aHR 0.96); the risk increased with reports of unprotected sex work
      (aHR 1.61) and unprotected receptive anal sex (aHR 2.63). All aHRs have P values
      <0.05. CONCLUSIONS: MSM/TW experience high incidence of HIV. Up-to-date
      prevalence and incidence information and identifying factors associated with
      infection can help develop a more effective combination prevention response.

PMID- 25950209
TI  - Race and the Public Health Impact Potential of Pre-Exposure Prophylaxis in the
      United States.

PMID- 25950208
TI  - Implementation and Operational Research: A Time-Motion Analysis of HIV
      Transmission Prevention Counseling and Antiretroviral Adherence Messages in
      Western Kenya.
AB  - BACKGROUND: Shortages of health workers and large number of HIV-infected persons
      in Africa mean that time to provide antiretroviral therapy (ART) adherence and
      other messages to patients is limited. METHODS: Using time-motion methodology, we
      documented the intensity and nature of counseling delivered to patients. The
      study was conducted at a rural and an urban HIV clinic in western Kenya. We
      recorded all activities of 190 adult patients on ART during their return clinic
      visits to assess type, frequency, and duration of counseling messages. RESULTS:
      Mean visit length for patients at the rural clinic was 44.5 (SD = 27.9) minutes
      and at urban clinic was 78.2 (SD = 42.1) minutes. Median time spent receiving any
      counseling during a visit was 4.07 minutes [interquartile range (IQR), 1.57-7.33]
      at rural and 3.99 (IQR, 2.87-6.25) minutes at urban, representing 11% and 8% of
      total mean visit time, respectively. Median time patients received ART adherence
      counseling was 1.29 (IQR, 0.77-2.83) minutes at rural and 1.76 (IQR, 1.23-2.83)
      minutes at urban (P = 0.001 for difference). Patients received a median time of
      0.18 (0-0.72) minutes at rural and 0.28 (IQR, 0-0.67) minutes at urban clinic of
      counseling regarding contraception and pregnancy. Most patients in the study did
      not receive any counseling regarding alcohol/substance use, emerging risks for
      ongoing HIV transmission. CONCLUSIONS: Although ART adherence was discussed with
      most patients, time was limited. Reproductive counseling was provided to only
      half of the patients, and "positive prevention" messaging was minimal. There are
      strategic opportunities to enhance counseling and information received by clients
      within HIV programs in resource-limited settings.

PMID- 25950210
TI  - Atypical glandular cells of undetermined significance: implications for
      management in a dysplasia clinic.
AB  - OBJECTIVE: The natural evolution of atypical glandular cells of undetermined
      significance (AGUS) within a dysplasia clinic population has not yet been
      studied. The purpose of this study was to determine the outcome of cervico
      vaginal smears with the diagnosis of AGUS from dysplasia clinic patients.
      MATERIAL AND METHODS: The cytopathological files of the Ottawa Civic Hospital
      were reviewed retrospectively from January 1993 to December 1995. In 59 dysplasia
      clinic patients, AGUS was diagnosed on one or more cervico-vaginal smears.
      Histological follow-up was available from 34 patients. Cytological follow-up was
      available on an additional 17 patients. RESULTS: Nineteen patients had clinically
      significant lesions. In eight patients, squamous intraepithelial neoplasia was
      diagnosed; in five, adenocarcinoma in situ; in another five, adenocarcinoma; and,
      in one patient, endometrial hyperplasia with atypia. In 15 patients, follow-up
      was negative. CONCLUSION: In a dysplasia clinic population in whom there was a
      cytological diagnosis of AGUS, we found 32% had significant pathology. Of these
      patients, 53% had glandular pathology. Based on our experience, histological
      assessment of the endocervix is suggested in these patients.

PMID- 25950211
TI  - Subepithelial angiogenesis in cervical intraepithelial neoplasia.
AB  - OBJECTIVE: A retrospective study was performed to determine whether the degree of
      angiogenesis progressively increases with the grade of cervical intraepithelial
      neoplasia (CIN). METHODS: Forty-one patients with CIN (9 with CIN1; 12 with CIN2;
      20 with CIN3) noted on cone biopsy were identified, and their charts were
      reviewed. Patients diagnosed with CIN were compared to nine control patients who
      had undergone hysterectomies for benign indications. Original surgical specimens
      were obtained for each patient, and new slides were prepared for staining with
      anti-factor VIII. The number of subepithelial microvessels in four separate high
      power (200*) fields was averaged for each specimen as an indirect measurement of
      the degree of angiogenesis. RESULTS: The mean number (+/- SD) of subepthelial
      blood vessels in the control group was 12.2 +/- 2.7 as compared with 23.5 +/- 5.5
      for patients with CIN1; 25.5 +/- 10.2 for those with CIN2; and 24.3 +/- 8.7 for
      women with CIN3. Analysis of variance revealed a significant difference in the
      mean number of blood vessels between groups (p = .0015). Multiple comparisons
      testing indicated that the mean blood vessel counts in CIN1, CIN2, and CIN3 were
      significantly higher as compared to controls (p < .05). CONCLUSIONS: The number
      of subepithelial microvessels is increased in CIN. This finding suggests that the
      transition of normal cervical tissue to preinvasive disease involves
      angiogenesis.

PMID- 25950212
TI  - Colposcopy Quality Control: Establishing Colposcopy Criterion Standards for the
      National Cancer Institute ALTS Trial Using Cervigrams.
AB  - OBJECTIVES: The colposcopy quality control (QC) group of the Atypical Squamous
      Cells of Undetermined Significance-Low-Grade Squamous Intraepithelial Lesions
      (ASCUS/ LSIL) Triage Study (ALTS) monitors colposcopists at four clinical centers
      by direct observation and indirectly by assessment of digitized computer
      colposcopic images transferred nightly by modem. The purpose of this preclinical
      study was to determine the agreement among colposcopy QC monitors' colposcopic
      impressions and biopsy site placement through evaluation of cervical photographic
      images. MATERIALS AND METHODS: A nonparticipant selected 100 Cervigram slides
      representing four pathologically confirmed categories: cervical intraepihelial
      neoplasia 1(CIN), CIN2 and CIN3, normal, and cancer. our colposcopy QC monitors
      and two certified Cervigram evaluators independently interpreted the images for
      colpocopic impression on two separate occasions. Measures of agreement were
      calculated for intraobserver, pairwise interobserver, and observer versus
      histological diagnoses. Participants also indicated the most severe biopsy site
      by marking an chi on a 4 * 6-inch color print duplication. Mean distances between
      biopsy site annotations for each pair of evaluators were calculated. RESULTS: The
      ALTS observer agreement with histology ranged from 75.3% (K = .66) to 47.4% (K =
      .36) for the first evaluation and 71.1 % (K = .63) to 50.5% (K = .38) for the
      second evaluation. ALTS interobserver agreement varied between 71 % and 57% for
      the first interpretation and 76% and I2% for the second evaluation. ALTS
      intraobserver agreement varied from 86% (K = .86) to 68.0% (K = .60). The mean
      listances between biopsy site annotations for each pair of ALTS observers varied
      from 0.99 +/- 0.93 mm to 1.44 +/- 1.19 nm. CONCLUSIONS: The ALTS colposcopy QC
      monitors achieved poor to good observer agreement with histology, fair to
      excellent interobserver agreement, and good to excellent intraobserver agreement
      in assessing the severity of cervical images. These levels of agreement are
      similar to many reported by pathologists for cervical cytology and histology
      interpretations. Monitors also demonstrated a very narrow variation of distance
      (< 2 mm) for ideal biopsy site placement.

PMID- 25950213
TI  - Neural network-based screening of atypical squamous cells of undetermined
      significance.
AB  - OBJECTIVES: To determine the usefulness of computerized rescreening for detecting
      high-grade cervical intraepithelial neoplasia (CIN) in patients with cytological
      evidence of atypical squamous cells of undertermined significance (ASCUS).
      METHODS: One hundred and eight patients with ASCUS cytology who had undergone
      colposcopy had their Papanicolaou smears reviewed using PAPNET, a neural network
      based instrument. RESULTS: Twenty (18.5%) of the 108 slides were reclassified to
      a higher-grade lesion. Analysis showed sensitivity (77.8%), specificity (86.9%),
      and positive (35%) and negative (97.7%) predictive values for detection of high
      grade CIN. CONCLUSIONS: PAPNET neural network-based rescreening of ASCUS smears
      identifies patients with high-grade cancer precursors. It may be a triage test
      for ASCUS cytology.

PMID- 25950214
TI  - Validation of the ThinPrep Papanicolaou Test for Cervical Cancer Diagnosis.
AB  - OBJECTIVES: Although the accuracy of the Thin-Prep Papanicolaou (Pap) Test has
      been demonstrated in the detection of precursor lesions to cervical cancer, its
      performance in identifying invasive cancer has not been adequately evaluated.
      These studies were designed to determine the effectiveness of the ThinPrep method
      in diagnosing invasive cervical cancer. MATERIALS AND METHODS: In four clinical
      studies, 47 cases of cervical cancer were processed by both conventional and
      ThinPrep techniques, and the cytological diagnoses and detection rates were
      compared. Additional studies evaluated the potential of cell loss during the
      ThinPrep filtration process. RESULTS: A diagnosis of cancer was made in 45 cases
      (95.7%) by the ThinPrep method and in 44 cases by conventional Pap smear (93.6%).
      In the two cases not diagnosed by the ThinPrep method, one was diagnosed as
      atypical squamous cells of undetermined significance and one as atypical
      glandular cells of undetermined significance. In the conventional smears, one of
      the three cases not identified as cancer was atypical squamous cells of
      undetermined significance, and the other two cases were unsatisfactory. In
      addition, the ability of the ThinPrep method to demonstrate tumor diathesis and
      to retain diagnostic cells by the filtration process was confirmed. CONCLUSIONS:
      These studies indicate that the ThinPrep method is at least equivalent to the
      conventional Pap smear method for the demonstration of squarnous cell carcinoma,
      adenocarcinoma, and other cervical malignancies.

PMID- 25950215
TI  - Economic evaluation of hybrid capture human papillomavirus testing in women with
      low-grade papanicolaou smear abnormalities.
AB  - OBJECTIVES: Our aim was to determine the cost-effectiveness of three strategies
      for detecting cervical intraepithelial neoplasia 2 and 3 after a determination of
      atypical squamous cells of undetermined significance or low-grade squamous
      intraepithelial lesion on screening Papanicolaou (Pap) smear. METHODS: Single
      repeat Pap smear. Hybrid Capture testing for human papillomavirus, and immediate
      colposcopy were compared. A theoretical decision analysis model was constructed
      with 10,000 women in each group. Costs and outcomes are those of diagnosis and
      treatment of cervical intraepithelial neoplasia (CIN) 2 or 3. Outcome
      probabilities and utilization data were obtained from a literature review and
      expert opinion. RESULTS: Repeat smear detected 1,125 cases, Hybrid Capture, 1,350
      cases, and colposcopy, 1,482 cases of CIN2 or CIN3, costing $1,490,000,
      $1,980,000, and $2,420,000, respectively. Incremental cost per high-grade
      dysplasia was $2,178 for Hybrid Capture and $3,333 for colposcopy. Sensitivity
      analyses that test management efficiencies are reported. CONCLUSIONS: More
      effective strategies are more costly. However, if costs saved by preventing
      invasive cancers are included, all three strategies may be cost-saving.

PMID- 25950216
TI  - Effectiveness of 5-Fluorouracil in the treatment of vaginal intraepithelial
      neoplasia in a mexican population.
AB  - OBJECTIVE: Our purpose was to determine the effectiveness of 5-fluorouracil (5
      FU) in the treatment of vaginal intraepithelial neoplasia (VaIN) in a Mexican
      population. MATERIALS AND METHODS: The study was performed in 30 patients with a
      mean age of 54 years and previous diagnoses from reviewed records and
      histopathology slides selected from a group of 65 patients with VaIN from 1980 to
      1997. Patients received intravaginal treatment with 5-FU, 1.5 g once weekly for
      10 weeks, and all patients were followed up for a 1-year minimum. Papanicolaou
      smear and colposcopy were performed, as was biopsy when indicated. RESULTS:
      Twenty-eight (93%) patients with VaIN had prior or concurrent anogenital squamous
      neoplasia, including 5 with invasive cervical carcinoma and 23 with cervical
      intraepithelial neoplasia. In 23 of 30 treated patients (77%), VaIN went into
      remission after a single treatment; in 3, (10%), it went into remission after two
      treatments; 3 (10%) had recurrent VaIN 3; and in 1 (3%), it progressed to
      invasive vaginal cancer. The treatment was well tolerated. CONCLUSIONS: We
      conclude that 5-FU is an option choice for VaIN treatment. It is effective, with
      minimal side effects. Its use should be confined to treating extensive or
      multifocal high-grade VaIN.

PMID- 25950218
TI  - Low-Grade and High-Grade Lesions in Cytological and Histological Diagnoses:
      What's in a Name?

PMID- 25950217
TI  - Fertility and pregnancy outcome after treatment for cervical intraepithelial
      neoplasia.
AB  - Fertility and pregnancy outcomes are important concerns of reproductive-age women
      undergoing treatment for cervical intraepithelial neoplasia (CIN). Despite this
      concern, very few controlled studies are examining this relationship. With the
      exception of large-cone biopsies, no evidence confirms that commonly used
      treatment modalities for CIN have a detrimental effect on fertility. Some CIN
      treatments are reported to be associated with preterm deliveries, low birth
      weight, and an increase in instrumental deliveries. Because smoking and low
      socioeconomic status are also associated with CIN, the value of any study not
      controlling for these factors is limited. Large-cone biopsies are associated with
      increased numbers of preterm deliveries and midtrimester pregnancy losses. The
      relationship of smaller-cone biopsies to preterm delivery is controversial.
      Cryotherapy does not affect pregnancy outcome, but the evidence is limited.
      Stronger evidence shows no difference in pregnancy outcome after laser surgery or
      electrosurgical loop excision. To be valuable, future studies should control for
      smoking and socioeconomic factors. 

PMID- 25950219
TI  - Home study course: autumn 1998.

PMID- 25950220
TI  - The american society for colposcopy and cervical pathology.

PMID- 25950221
TI  - Polyarteritis nodosa of the vagina mimicking vaginal carcinoma.
AB  - A case report is presented in which a patient is found to have an ulcerated
      vaginal mass that is histologically diagnosed as polyarteritis nodosa (PAN).
      Treatment with colchicine brought about sustained regression of the disease
      Approximately 34 cases of PAN involving the female genital tract have been
      published in the world literature. This represents the first report of vaginal
      involvement by a lesion of PAN. 

PMID- 25950222
TI  - Pelvic inflammatory disease after cryotherapy.
AB  - OBJECTIVE: The purpose of this article is to present a case of pelvic
      inflammatory disease (PID) after cryotherapy and to discuss the need for routine
      testing of gonococcal and chlamydial infections at the time of cryotherapy and
      prophylactic antibiotics. METHODS AND MATERIALS: A 21-year-old nulliparous woman
      was treated with cryotherapy for low-grade squamous intraepithelial lesion.
      RESULT: Two days after the procedure, she developed PID. She was hospitalized and
      treated with intravenous antibiotics. CONCLUSION: Cryotherapy offers a convenient
      and inexpensive form of treatment for cervical intraepithelial neoplasia when the
      lesion is confined to the ectocervix and of appropriate size and severity.
      Cryotherapy can be performed in a physician's office and is free of major
      complications. However, PID after cryotherapy has been documented in the
      literature. PID may lead to significant morbidity in terms of infertility,
      ectopic pregnancy, and chronic pelvic pain. Routine testing for gonococcal and
      chlamydial infection at the time of cryotherapy and prophylactic antibiotics may
      help to prevent PID after cryotherapy.

PMID- 25950223
TI  - Clinical question: ask the experts.

PMID- 25950225
TI  - Appropriate use of leep interventions.

PMID- 25950224
TI  - Is endocerevical sampling necessary?

PMID- 25950226
TI  - In reply.

PMID- 25950227
TI  - Colposcoping patients after leep.

PMID- 25950230
TI  - Antifibrinolytic Therapy for Cardiac Surgery: An Update.

PMID- 25950231
TI  - Effect of application of a PVP-iodine solution before and during subgingival
      ultrasonic instrumentation on post-treatment bacteraemia: a randomized single
      centre placebo-controlled clinical trial.
AB  - BACKGROUND: To assess the effect of concomitant subgingival rinsing with 10% PVP
      iodine during subgingival instrumentation on the prevalence and magnitude of
      bacteraemia of oral origin. MATERIALS AND METHODS: Subgingival instrumentation
      was performed with water or PVP-iodine rinse in patients with periodontitis.
      Prior to instrumentation, subjects gargled for 1 min with the allocated liquid.
      Pockets were then rinsed for 1 min and subgingivally instrumented with liquid
      cooled (water/PVP-iodine) ultrasonic scalers (1 min). Two minutes later, a blood
      sample from the arm vein was drawn using a lysis centrifugation blood culture
      system for quantitative microbiological analysis. Non-parametric statistical
      tests were performed to assess differences in the prevalence and extent of
      bacteraemia between groups. RESULTS: Of the 19 samples in each group, oral-borne
      bacteraemia was detected in 10 of the control and 2 of the test samples. With an
      average of 3.0 [1; 5] colony forming units, significantly less bacteria and
      bacteraemia were found in the test group compared to the controls (12.2 [1; 46])
      (p = 0.003). Anaerobic bacteria were not found in the test group. CONCLUSIONS:
      Bacteraemia after subgingival instrumentation with concomitant PVP-iodine rinsing
      is reduced but not eliminated. Therefore, it might be recommended for patients at
      a high risk of endocarditis or infection of endoprostheses. However, preventive
      antibiotic treatment should not be omitted.

PMID- 25950232
TI  - The introduction of buprenorphine-naloxone film in opioid substitution therapy in
      Australia: Uptake and issues arising from changing buprenorphine formulations.
AB  - INTRODUCTION AND AIMS: Buprenorphine-naloxone (BNX) film for opioid dependence
      treatment was introduced in Australia in 2011. A key difference in State policy
      approaches saw transfer from BNX tablets to BNX film mandated in South Australia
      (SA) with New South Wales (NSW) and Victoria (VIC) having less stringent
      policies. This study examined (i) how initiations and transfers were implemented,
      (ii) the profile and predictors of adverse effects as self-reported by BNX film
      clients, and (iii) dosing issues. DESIGN AND METHODS: Survey of 334 buprenorphine
      (BPN), BNX tablet and BNX film clients and semi-structured interviews with 39 key
      experts (KEs) in 2012. Comparisons are made between clients interviewed in SA
      versus NSW and VIC combined. RESULTS: Among the 180 current BNX film clients, 23%
      started treatment on BNX film, 18% requested a transfer to BNX film and 59% (n =
      106) reported their clinic/prescriber recommended transfer to BNX film. Among
      clients who were offered but refused a transfer to BNX film (n = 66), the most
      common reason was 'I am happy with my current treatment and do not see a reason
      to change' (53%). Some opioid substitution therapy clients and KE viewed
      transfers as 'forced' (i.e. no choice of buprenorphine formulation).
      Multivariable regression showed residing in SA (vs. NSW/VIC) and a shorter length
      of current treatment episode were associated with more BNX film-attributed
      adverse effects but clinic/prescriber-recommended transfer was not. DISCUSSION
      AND CONCLUSIONS: The introduction of BNX film in Australia varied across States.
      A perception of restricted choice in medication may have undermined initial
      acceptance in SA.

PMID- 25950233
TI  - Napping facilitates word learning in early lexical development.
AB  - Little is known about the role that night-time sleep and daytime naps play in
      early cognitive development. Our aim was to investigate how napping affects word
      learning in 16-month-olds. Thirty-four typically developing infants were assigned
      randomly to nap and wake groups. After teaching two novel object-word pairs to
      infants, we tested their initial performance with an intermodal preferential
      looking task in which infants are expected to increase their target looking time
      compared to a distracter after hearing its auditory label. A second test session
      followed after approximately a 2-h delay. The delay contained sleep for the nap
      group or no sleep for the wake group. Looking behaviour was measured with an
      automatic eye-tracker. Vocabulary size was assessed using the Oxford
      Communicative Development Inventory. A significant interaction between group and
      session was found in preferential looking towards the target picture. The
      performance of the nap group increased after the nap, whereas that of the wake
      group did not change. The gain in performance correlated positively with the
      expressive vocabulary size in the nap group. These results indicate that daytime
      napping helps consolidate word learning in infancy. 

PMID- 25950234
TI  - The Knowledge Gap Versus the Belief Gap and Abstinence-Only Sex Education.
AB  - The knowledge gap hypothesis predicts widening disparities in knowledge of
      heavily publicized public affairs issues among socioeconomic status groups. The
      belief gap hypothesis extends the knowledge gap hypothesis to account for
      knowledge and beliefs about politically contested issues based on empirically
      verifiable information. This analysis of 3 national surveys shows belief gaps
      developed between liberals and conservatives regarding abstinence-only sex
      education; socioeconomic status-based knowledge gaps did not widen. The findings
      partially support both belief gap and knowledge gap hypotheses. In addition, the
      unique contributions of exposure to Fox News, CNN, and MSNBC in this process were
      investigated. Only exposure to Fox News was linked to beliefs about abstinence
      only sex education directly and indirectly through the cultivation of
      conservative ideology. 

PMID- 25950235
TI  - An automated microfluidic platform for C. elegans embryo arraying, phenotyping,
      and long-term live imaging.
AB  - Studies of the real-time dynamics of embryonic development require a gentle
      embryo handling method, the possibility of long-term live imaging during the
      complete embryogenesis, as well as of parallelization providing a population's
      statistics, while keeping single embryo resolution. We describe an automated
      approach that fully accomplishes these requirements for embryos of Caenorhabditis
      elegans, one of the most employed model organisms in biomedical research. We
      developed a microfluidic platform which makes use of pure passive hydrodynamics
      to run on-chip worm cultures, from which we obtain synchronized embryo
      populations, and to immobilize these embryos in incubator microarrays for long
      term high-resolution optical imaging. We successfully employ our platform to
      investigate morphogenesis and mitochondrial biogenesis during the full embryonic
      development and elucidate the role of the mitochondrial unfolded protein response
      (UPR(mt)) within C. elegans embryogenesis. Our method can be generally used for
      protein expression and developmental studies at the embryonic level, but can also
      provide clues to understand the aging process and age-related diseases in
      particular. 

PMID- 25950236
TI  - NetworkAnalyst for statistical, visual and network-based meta-analysis of gene
      expression data.
AB  - Meta-analysis of gene expression data sets is increasingly performed to help
      identify robust molecular signatures and to gain insights into underlying
      biological processes. The complicated nature of such analyses requires both
      advanced statistics and innovative visualization strategies to support efficient
      data comparison, interpretation and hypothesis generation. NetworkAnalyst
      (http://www.networkanalyst.ca) is a comprehensive web-based tool designed to
      allow bench researchers to perform various common and complex meta-analyses of
      gene expression data via an intuitive web interface. By coupling well-established
      statistical procedures with state-of-the-art data visualization techniques,
      NetworkAnalyst allows researchers to easily navigate large complex gene
      expression data sets to determine important features, patterns, functions and
      connections, thus leading to the generation of new biological hypotheses. This
      protocol provides a step-wise description of how to effectively use
      NetworkAnalyst to perform network analysis and visualization from gene lists; to
      perform meta-analysis on gene expression data while taking into account multiple
      metadata parameters; and, finally, to perform a meta-analysis of multiple gene
      expression data sets. NetworkAnalyst is designed to be accessible to biologists
      rather than to specialist bioinformaticians. The complete protocol can be
      executed in ~1.5 h. Compared with other similar web-based tools, NetworkAnalyst
      offers a unique visual analytics experience that enables data analysis within the
      context of protein-protein interaction networks, heatmaps or chord diagrams. All
      of these analysis methods provide the user with supporting statistical and
      functional evidence. 

PMID- 25950237
TI  - The Phyre2 web portal for protein modeling, prediction and analysis.
AB  - Phyre2 is a suite of tools available on the web to predict and analyze protein
      structure, function and mutations. The focus of Phyre2 is to provide biologists
      with a simple and intuitive interface to state-of-the-art protein bioinformatics
      tools. Phyre2 replaces Phyre, the original version of the server for which we
      previously published a paper in Nature Protocols. In this updated protocol, we
      describe Phyre2, which uses advanced remote homology detection methods to build
      3D models, predict ligand binding sites and analyze the effect of amino acid
      variants (e.g., nonsynonymous SNPs (nsSNPs)) for a user's protein sequence. Users
      are guided through results by a simple interface at a level of detail they
      determine. This protocol will guide users from submitting a protein sequence to
      interpreting the secondary and tertiary structure of their models, their domain
      composition and model quality. A range of additional available tools is described
      to find a protein structure in a genome, to submit large number of sequences at
      once and to automatically run weekly searches for proteins that are difficult to
      model. The server is available at http://www.sbg.bio.ic.ac.uk/phyre2. A typical
      structure prediction will be returned between 30 min and 2 h after submission. 

PMID- 25950238
TI  - Long-Term Outcomes of Total Parathyroidectomy With or Without Autoimplantation
      for Hyperparathyroidism in Chronic Kidney Disease: A Meta-Analysis.
AB  - The aim of the present study was to compare total parathyroidectomy without
      autotransplantation (TPTX) versus total parathyroidectomy with
      autotransplantation (TPTX + AT) for renal hyperparathyroidism (RHPT) with respect
      to long-term outcomes. A literature search was undertaken using Medline and
      EMBASE from inception to December 2013. Data were analyzed using Review Manager
      version 5.0. A total of seven cohort studies comprising 931 patients were
      identified. Compared with TPTX + AT, patients in the TPTX group have lower
      "recurrence" (odds ratio (OR) 0.08, confidence interval (CI) 0.03 to 0.21; P <
      0.00001), lower "recurrence or persistence"(OR 0.11, 95% CI 0.05 to 0.25; P <
      0.00001), lower "requiring reoperation because of recurrence or persistence" (OR
      0.17, CI 0.06 to 0.54; P = 0.002), and higher "hypoparathyroidism" (OR 2.97, CI
      1.09 to 8.08; P = 0.03). None of the patients in these seven studies were
      recorded as having severe hypocalcemia or adynamic bone disease. Compared with
      TPTX + AT, TPTX is associated with lower "requiring reoperation because of
      recurrence or persistence" and without severe hypocalcemia or adynamic bone
      disease. 

PMID- 25950239
TI  - Tomographic Assessment of Bone Formation After the Collares Technique of
      Gingivoperiosteoplasty in Patients With Cleft Lip and Palate.
AB  - OBJECTIVES: This cross-sectional study sought to assess bone formation and
      spontaneous tooth eruption in a cohort of 25 consecutive patients aged 6 to 11
      years who underwent primary gingivoperiosteoplasty by the Collares technique.
      DESIGN: Cross-sectional study assessing bone formation in the cleft area using a
      within-group time series design. SETTING: Hospital de Clinicas de Porto Alegre
      (HCPA), a tertiary hospital in Brazil. PATIENTS: Twenty-five patients with
      nonsyndromic, complete unilateral cleft lip and palate, no comorbidities, and
      unerupted permanent canines. INTERVENTION: Cheiloplasty was performed by means of
      the Millard II technique, with the addition of a triangle at the mucocutaneous
      junction, vomer flap nasal floor closure, and wide subperiosteal elevation,
      followed by gingivoperiosteoplasty by the Collares technique. MAIN OUTCOME
      MEASURES: Cone-beam computed tomography was used to assess treatment effect. In a
      novel method, software was used to obtain two three-dimensional reconstructions,
      one each of the cleft and noncleft sides, enabling quantitative comparison of
      bone presence in the alveolar defect area. RESULTS: Of the 25 patients, 24
      achieved bone bridge formation. The cleft side had 75.1% (67.9%-82.3%) of the
      bone volume, 70.5% (53.1%-87.9%) of the height, and 63.3% (44.1%-82.5%) of the
      width of the noncleft side. Bone formation was 17.28% lower in patients with
      lateral incisor agenesis. CONCLUSION: Collares gingivoperiosteoplasty performed
      well as a technique for alveolar repair in patients with cleft lip and palate,
      allowing spontaneous eruption of deciduous and permanent lateral incisors through
      the bone bridge created.

PMID- 25950240
TI  - To space or not space? Interword spacing effects on Chinese children's reading
      materials.
AB  - This study investigated different Chinese on-screen text layouts to see if they
      improved the reading speed and comprehension of Taiwanese children. A number of
      different experimental treatments were used. These were: interword spacing
      (unspaced, semi-spaced and fully-spaced), text difficulty (easy and difficult)
      and text direction (vertical and horizontal). The experiment involved 84 children
      aged between 10 and 11 years old. In the experiment the children were asked to
      read articles. The time they took to read these articles was recorded. The
      children also partook in comprehension tests to determine how much they had
      understood about the articles they had read. The results showed that horizontal
      text was read more quickly than vertical text and was better comprehended. The
      results also showed that fully-spaced difficult text was read more quickly than
      semi-spaced difficult text, and unspaced difficult text was also better
      comprehended. Practitioner Summary: This experiment was conducted to explore the
      affects of interword spacing, text direction and text difficulty on the reading
      speeds and comprehension of on-screen traditional Chinese characters by Taiwanese
      children. It found that fully-spaced, horizontal text was the quickest and most
      comprehendible to read, regardless of text difficulty.

PMID- 25950241
TI  - Using "Tender" X-ray Ambient Pressure X-Ray Photoelectron Spectroscopy as A
      Direct Probe of Solid-Liquid Interface.
AB  - We report a new method to probe the solid-liquid interface through the use of a
      thin liquid layer on a solid surface. An ambient pressure XPS (AP-XPS) endstation
      that is capable of detecting high kinetic energy photoelectrons (7 keV) at a
      pressure up to 110 Torr has been constructed and commissioned. Additionally, we
      have deployed a "dip &pull" method to create a stable nanometers-thick aqueous
      electrolyte on platinum working electrode surface. Combining the newly
      constructed AP-XPS system, "dip &pull" approach, with a "tender" X-ray
      synchrotron source (2 keV-7 keV), we are able to access the interface between
      liquid and solid dense phases with photoelectrons and directly probe important
      phenomena occurring at the narrow solid-liquid interface region in an
      electrochemical system. Using this approach, we have performed electrochemical
      oxidation of the Pt electrode at an oxygen evolution reaction (OER) potential.
      Under this potential, we observe the formation of both Pt(2+) and Pt(4+)
      interfacial species on the Pt working electrode in situ. We believe this thin
      film approach and the use of "tender" AP-XPS highlighted in this study is an
      innovative new approach to probe this key solid-liquid interface region of
      electrochemistry. 

PMID- 25950242
TI  - Subjective response as a consideration in the pharmacogenetics of alcoholism
      treatment.
AB  - Currently available pharmacological treatments for alcoholism have modest
      efficacy and high individual variability in treatment outcomes, both of which
      have been partially attributed to genetic factors. One path to reducing the
      variability and improving the efficacy associated with these pharmacotherapies
      may be to identify overlapping genetic contributions to individual differences in
      both subjective responses to alcohol and alcoholism pharmacotherapy outcomes. As
      acute subjective response to alcohol is highly predictive of future alcohol
      related problems, identifying such shared genetic mechanisms may inform the
      development of personalized treatments that can effectively target converging
      pathophysiological mechanisms that convey risk for alcoholism. The focus of this
      review is to revisit the association between subjective response to alcohol and
      the etiology of alcoholism while also describing genetic contributions to this
      relationship, discuss potential pharmacogenetic approaches to target subjective
      response to alcohol in order to improve the treatment of alcoholism and examine
      conceptual and methodological issues associated with these topics, and outline
      future approaches to overcome these challenges. 

PMID- 25950243
TI  - Soret fishnet metalens antenna.
AB  - At the expense of frequency narrowing, binary amplitude-only diffractive optical
      elements emulate refractive lenses without the need of large profiles.
      Unfortunately, they also present larger Fresnel reflection loss than conventional
      lenses. This is usually tackled by implementing unattractive cumbersome designs.
      Here we demonstrate that simplicity is not at odds with performance and we show
      how the fishnet metamaterial can improve the radiation pattern of a Soret lens.
      The building block of this advanced Soret lens is the fishnet metamaterial
      operating in the near-zero refractive index regime with one of the edge layers
      designed with alternating opaque and transparent concentric rings made of
      subwavelength holes. The hybrid Soret fishnet metalens retains all the merits of
      classical Soret lenses such as low profile, low cost and ease of manufacturing.
      It is designed for the W-band of the millimeter-waves range with a subwavelength
      focal length FL = 1.58 mm (0.5lambda0) aiming at a compact antenna or radar
      systems. The focal properties of the lens along with its radiation
      characteristics in a lens antenna configuration have been studied numerically and
      confirmed experimentally, showing a gain improvement of ~2 dB with respect to a
      fishnet Soret lens without the fishnet metamaterial. 

PMID- 25950245
TI  - Generalized fidelity susceptibility at phase transitions.
AB  - In the present work, we investigate the intrinsic relation between quantum
      fidelity susceptibility (QFS) and the dynamical structure factor. We give a
      concise proof of the QFS beyond the perturbation theory. With the QFS in the
      Lehmann representation, we point out that the QFS is actually the negative-two
      power moment of dynamical structure factor and illuminate the inherent relation
      between physical quantities in the linear response theory. Moreover, we discuss
      the generalized fidelity susceptibility (GFS) of any quantum relevant operator,
      that may not be coupled to the driving parameter, and present similar scaling
      behaviors. Finally, we demonstrate that the QFS cannot capture the fourth-order
      quantum phase transition in a spin-1/2 anisotropic XY chain in the transverse
      alternating field, while a lower-order GFS can seize the criticalities. 

PMID- 25950244
TI  - Correlates of major depressive disorder with and without comorbid alcohol use
      disorder nationally in the veterans health administration.
AB  - BACKGROUND AND OBJECTIVES: This study assesses medical and psychiatric
      comorbidities, service utilization, and psychotropic medication prescriptions in
      veterans with comorbid major depressive disorder (MDD) and alcohol use disorder
      (AUD) relative to veterans with MDD alone. METHODS: Using cross-sectional
      administrative data (fiscal year [FY]2012: October 1, 2011-September 30, 2012)
      from the Veterans Health Administration (VHA), we identified veterans with a
      diagnosis of current (12-month) MDD nationally (N = 309,374), 18.8% of whom were
      also diagnosed with current (12-month) AUD. Veterans with both MDD and AUD were
      compared to those with MDD alone on sociodemographic characteristics, current (12
      month) medical and psychiatric disorders, service utilization, and psychotropic
      prescriptions. We then used logistic regression analyses to calculate odds ratio
      and 95% confidence interval of characteristics that were independently different
      between the groups. RESULTS: Dually diagnosed veterans with MDD and AUD, relative
      to veterans with MDD alone, had a greater number of comorbid health conditions,
      such as liver disease, drug use disorders, and bipolar disorder as well as
      greater likelihood of homelessness and higher service utilization. CONCLUSIONS
      AND SCIENTIFIC SIGNIFICANCE: Dually diagnosed veterans with MDD and AUD had more
      frequent medical and psychiatric comorbidities and more frequently had been
      homeless. These data suggest the importance of assessing the presence of comorbid
      medical/psychiatric disorders and potential homelessness in order to provide
      appropriately comprehensive treatment to dually diagnosed veterans with MDD and
      AUD and indicate a need to develop more effective treatments for combined
      disorders.

PMID- 25950246
TI  - Hydration, fluid regulation and the eye: in health and disease.
AB  - Variation in systemic hydration status, namely chronic systemic hypohydration or
      dehydration, can influence the development of several chronic non-ophthalmic
      diseases. Owing to the eye's high water content and unique system of fluid
      regulation, we hypothesized that hydration status may affect the eye in health
      and disease states. Therefore, we performed a systematic review of the current
      evidence implicating changes in hydration and their association with ocular
      physiology and morphological characteristics. We also reviewed relevant clinical
      correlations of changes in hydration and major common eye diseases. Our findings
      suggest that systemic hydration status broadly affects a variety of ocular
      pathophysiologic processes and disease states. For example, dehydration may be
      associated with development of dry eye syndrome, cataract, refractive changes and
      retinal vascular disease. On the other hand, excessive hydration is associated
      with some ocular diseases. Tear fluid osmolarity may be an effective marker of
      systemic hydration status. Recent studies implicate chronic renin-angiotensin
      aldosterone system activation in the pathogenesis of diabetic retinopathy and
      glaucoma but also suggest its antagonism may be a useful therapeutic target. Our
      findings indicate that assessment of hydration status may be an important
      consideration in the management of patients with chronic eye diseases and
      undergoing eye surgery. Further research investigating the role of acute and
      chronic changes in hydration in individuals with and without ocular disease is
      warranted. 

PMID- 25950247
TI  - Prepubertal-Onset Vulvar Lichen Sclerosus: The Importance of Maintenance Therapy
      in Long-Term Outcomes.
AB  - BACKGROUND: There is sufficient published data on induction treatment with potent
      topical corticosteroid (TCS) in childhood vulvar lichen sclerosus (VLS) but
      limited data on long-term management. VLS has been shown to extend beyond
      menarche and repercussions of suboptimal long-term control may be devastating and
      permanent. This single-center retrospective study reviewed outcomes of long-term
      treatment using individualized regimens with target outcome of complete objective
      normality. METHODS: Forty-six girls with prepubertal-onset VLS were studied for
      demographic data, previous treatment, induction and maintenance treatment,
      clinical response and compliance. Photographic records were available for all
      patients. The cohort was divided into two groups: adherent (using treatment all
      or most of the time) and non-adherent (using treatment some or less of the time).
      RESULTS: Twenty-six patients (56%) had received prior treatment however only
      three had achieved disease control using daily potent TCS. Twelve patients (26%)
      had scarring on presentation. All achieved initial objective disease suppression
      with induction treatment using potent TCS. Thirty-one of 33 adherent patients
      (93.93%) sustained complete disease remission with no progression or scarring. In
      contrast, 1 of the 13 nonadherent patients (8%) achieved complete disease
      remission (p < 0.001), 9 of the 13 (69.23%) experienced disease progression (p <
      0.001) and 3 of the 13 (23%) developed scarring during follow-up. Those with
      established scarring on presentation did not recover with treatment. CONCLUSION:
      Our data support previous studies regarding initial treatment with potent TCS but
      additionally suggest maintenance treatment with individualized regimens that
      achieve objective normality in addition to symptom control provide optimal
      outcomes.

PMID- 25950248
TI  - Inhibition of tomato shoot growth by over-irrigation is linked to nitrogen
      deficiency and ethylene.
AB  - Although physiological effects of acute flooding have been well studied, chronic
      effects of suboptimal soil aeration caused by over-irrigation of containerized
      plants have not, despite its likely commercial significance. By automatically
      scheduling irrigation according to soil moisture thresholds, effects of over
      irrigation on soil properties (oxygen concentration, temperature and moisture),
      leaf growth, gas exchange, phytohormone [abscisic acid (ABA) and ethylene]
      relations and nutrient status of tomato (Solanum lycopersicum Mill. cv. Ailsa
      Craig) were studied. Over-irrigation slowly increased soil moisture and decreased
      soil oxygen concentration by 4%. Soil temperature was approximately 1 degrees C
      lower in the over-irrigated substrate. Over-irrigating tomato plants for 2 weeks
      significantly reduced shoot height (by 25%) and fresh weight and total leaf area
      (by 60-70%) compared with well-drained plants. Over-irrigation did not alter
      stomatal conductance, leaf water potential or foliar ABA concentrations,
      suggesting that growth inhibition was not hydraulically regulated or dependent on
      stomatal closure or changes in ABA. However, over-irrigation significantly
      increased foliar ethylene emission. Ethylene seemed to inhibit growth, as the
      partially ethylene-insensitive genotype Never ripe (Nr) was much less sensitive
      to over-irrigation than the wild type. Over-irrigation induced significant foliar
      nitrogen deficiency and daily supplementation of small volumes of 10 mM Ca(NO3 )2
      to over-irrigated soil restored foliar nitrogen concentrations, ethylene emission
      and shoot fresh weight of over-irrigated plants to control levels. Thus reduced
      nitrogen uptake plays an important role in inhibiting growth of over-irrigated
      plants, in part by stimulating foliar ethylene emission. 

PMID- 25950249
TI  - A genomewide catalogue of single nucleotide polymorphisms in white-beaked and
      Atlantic white-sided dolphins.
AB  - The field of population genetics is rapidly moving into population genomics as
      the quantity of data generated by high-throughput sequencing platforms increases.
      In this study, we used restriction-site-associated DNA sequencing (RADSeq) to
      recover genomewide genotypes from 70 white-beaked (Lagenorhynchus albirostris)
      and 43 Atlantic white-sided dolphins (L. acutus) gathered throughout their north
      east Atlantic distribution range. Both species are at a high risk of being
      negatively affected by climate change. Here, we provide a resource of 38,240 RAD
      tags and 52,981 nuclear SNPs shared between both species. We have estimated
      overall higher levels of nucleotide diversity in white-sided (pi = 0.0492 +/-
      0.0006%) than in white-beaked dolphins (pi = 0.0300 +/- 0.0004%). White-sided
      dolphins sampled in the Faroe Islands, belonging to two pods (N = 7 and N = 11),
      showed similar levels of diversity (pi = 0.0317 +/- 0.0007% and 0.0267 +/-
      0.0006%, respectively) compared to unrelated individuals of the same species
      sampled elsewhere (e.g. pi = 0.0285 +/- 0.0007% for 11 Scottish individuals). No
      evidence of higher levels of kinship within pods can be derived from our
      analyses. When identifying the most likely number of genetic clusters among our
      sample set, we obtained an estimate of two to four clusters, corresponding to
      both species and possibly, two further clusters within each species. A higher
      diversity and lower population structuring was encountered in white-sided
      dolphins from the north-east Atlantic, in line with their preference for pelagic
      waters, as opposed to white-beaked dolphins that have a more patchy distribution,
      mainly across continental shelves.

PMID- 25950250
TI  - Brain morphology in juvenile myoclonic epilepsy and absence seizures.
AB  - OBJECTIVE: We evaluated the differences in brain morphology among patients with
      juvenile myoclonic epilepsy according to the occurrence of absence seizures.
      MATERIALS AND METHODS: Twenty-one juvenile myoclonic epilepsy patients with (n =
      6) and without (n = 15) absence seizures were enrolled. We analyzed whole-brain
      T1-weighted magnetic resonance imaging using FreeSurfer 5.1. Measures of cortical
      morphology, such as thickness, surface area, volume, and curvature, and the
      volumes of subcortical structures, the cerebellum, and cerebrum, were compared
      between the groups. Moreover, we quantified correlations between clinical
      variables and each measures of abnormal brain morphology. RESULTS: Compared to
      normal controls, patients without absence seizures demonstrated thinning of the
      cortical thickness in the right hemisphere, including the post-central, lingual,
      orbitofrontal, and lateral occipital cortex. Compared to normal controls,
      patients with absence seizures had more widespread thinning of the cortical
      thickness, including the right post-central, lingual, orbitofrontal, and lateral
      occipital cortexes as well as the right inferior temporal cortex. Additionally,
      the volume of cerebellar white matter in patients without absence seizures was
      significantly smaller than that in normal controls. Patients with absence
      seizures had a much smaller cerebellar white matter volume than normal controls
      or patients without absence seizures. Moreover, there was significantly positive
      correlation between the age of seizure onset and the volume of cerebellar white
      matter in patients with juvenile myoclonic epilepsy. CONCLUSIONS: We demonstrated
      that there were significant brain morphology differences in patients with
      juvenile myoclonic epilepsy according to the presence of absence seizures. These
      findings support the hypothesis that juvenile myoclonic epilepsy may be a
      heterogeneous syndrome.

PMID- 25950251
TI  - Increases in hepatitis C virus infection related to injection drug use among
      persons aged <=30 years - Kentucky, Tennessee, Virginia, and West Virginia, 2006
      2012.
AB  - Hepatitis C virus (HCV) infection is the most common blood-borne infection in the
      United States, with approximately three million persons living with current
      infection. Percutaneous exposure to contaminated blood is the most efficient mode
      of transmission, and in the United States, injection drug use (IDU) is the
      primary risk factor for infection. State surveillance reports from the period
      2006-2012 reveal a nationwide increase in reported cases of acute HCV infection,
      with the largest increases occurring east of the Mississippi River, particularly
      among states in central Appalachia. Demographic and behavioral data accompanying
      these reports show young persons (aged <=30 years) from nonurban areas
      contributed to the majority of cases, with about 73% citing IDU as a principal
      risk factor. To better understand the increase in acute cases of HCV infection
      and its correlation to IDU, CDC examined surveillance data for acute case reports
      in conjunction with analyzing drug treatment admissions data from the Treatment
      Episode Data Set-Admissions (TEDS-A) among persons aged <=30 years in four states
      (Kentucky, Tennessee, Virginia, and West Virginia) for the period 2006-2012.
      During this period, significant increases in cases of acute HCV infection were
      found among persons in both urban and nonurban areas, with a substantially higher
      incidence observed each year among persons residing in nonurban areas. During the
      same period, the proportion of treatment admissions for opioid dependency
      increased 21.1% in the four states, with a significant increase in the proportion
      of persons admitted who identified injecting as their main route of drug
      administration (an increase of 12.6%). Taken together, these increases indicate a
      geographic intersection among opioid abuse, drug injecting, and HCV infection in
      central Appalachia and underscore the need for integrated health services in
      substance abuse treatment settings to prevent HCV infection and ensure that those
      who are infected receive medical care. 

PMID- 25950252
TI  - Identification and Linkage to Care of HCV-Infected Persons in Five Health Centers
      - Philadelphia, Pennsylvania, 2012-2014.
AB  - Approximately three million persons in the United States are infected with
      hepatitis C virus (HCV), a blood-borne pathogen that is an increasing cause of
      liver disease and mortality in the United States. Treatments for HCV are
      curative, of short duration, and have few associated side effects, increasing the
      importance of identifying HCV-infected persons. Many persons with HCV infection
      were infected decades ago, before implementation of prevention measures and most
      are unaware of their infection, regardless of when it occurred. Most newly
      diagnosed cases are associated with injection drug use. Persons born during 1945
      1965 have a fivefold higher risk of HCV infection than other adults and the
      highest risk for HCV-related morbidity and mortality. CDC recommends testing for
      this group, for persons who inject drugs, and others at risk for HCV infection.
      From October 2012 through July 2014, the National Nursing Centers Consortium
      (NNCC) carried out a project to integrate routine HCV testing and linkage-to-care
      in five federally qualified health centers in Philadelphia, PA, that primarily
      serve homeless persons and public housing residents. During the project period,
      4,514 patients across the five centers were tested for HCV. Of these, 595 (13.2%)
      were HCV-antibody positive and 550 (92.4%) had a confirmatory HCV-RNA test
      performed. Of those who had a confirmatory HCV-RNA test performed, 390 (70.9%)
      were identified as having current (i.e., chronic) HCV infection (overall
      prevalence = 8.6%). Of those currently infected with HCV, 90% were informed of
      their status, 78% were referred to an HCV care specialist, and 62% went to the
      referred specialist for care. Replicable system modifications that improved HCV
      testing and care included enhancements to electronic medical records (EMRs),
      simplification of HCV testing protocols, and addition of a linkage-to-care
      coordinator. Findings from this project highlight the need for innovative
      strategies for HCV testing, care, and treatment, as well as the important role of
      community health centers in expanding access for patient populations
      disproportionately affected by HCV infection. 

PMID- 25950253
TI  - Cancer screening test use - United States, 2013.
AB  - Regular breast, cervical, and colorectal cancer (CRC) screening with timely and
      appropriate follow-up and treatment reduces deaths from these cancers. Healthy
      People 2020 targets for cancer screening test use have been established, based on
      the most recent U.S. Preventive Services Task Force (USPSTF) guidelines. National
      Health Interview Survey (NHIS) data are used to monitor progress toward the
      targets. CDC used the 2013 NHIS, the most recent data available, to examine
      breast, cervical, and CRC screening use. Although some demographic subgroups
      attained targets, screening use overall was below the targets with no
      improvements from 2010 to 2013 in breast, cervical, or CRC screening use.
      Cervical cancer screening declined from 2010 to 2013. Increased efforts are
      needed to achieve targets and reduce screening disparities. 

PMID- 25950254
TI  - Vital signs: leading causes of death, prevalence of diseases and risk factors,
      and use of health services among Hispanics in the United States - 2009-2013.
AB  - BACKGROUND: Hispanics and Latinos (Hispanics) are estimated to represent 17.7% of
      the U.S. population. Published national health estimates stratified by Hispanic
      origin and nativity are lacking. METHODS: Four national data sets were analyzed
      to compare Hispanics overall, non-Hispanic whites (whites), and Hispanic
      country/region of origin subgroups (Hispanic origin subgroups) for leading causes
      of death, prevalence of diseases and associated risk factors, and use of health
      services. Analyses were generally restricted to ages 18-64 years and were further
      stratified when possible by sex and nativity. RESULTS: Hispanics were on average
      nearly 15 years younger than whites; they were more likely to live below the
      poverty line and not to have completed high school. Hispanics showed a 24% lower
      all-cause death rate and lower death rates for nine of the 15 leading causes of
      death, but higher death rates from diabetes (51% higher), chronic liver disease
      and cirrhosis (48%), essential hypertension and hypertensive renal disease (8%),
      and homicide (96%) and higher prevalence of diabetes (133%) and obesity (23%)
      compared with whites. In all, 41.5% of Hispanics lacked health insurance (15.1%
      of whites), and 15.5% of Hispanics reported delay or nonreceipt of needed medical
      care because of cost concerns (13.6% of whites). Among Hispanics, self-reported
      smoking prevalences varied by Hispanic origin and by sex. U.S.-born Hispanics had
      higher prevalences of obesity, hypertension, smoking, heart disease, and cancer
      than foreign-born Hispanics: 30% higher, 40%, 72%, 89%, and 93%, respectively.
      CONCLUSION: Hispanics had better health outcomes than whites for most analyzed
      health factors, despite facing worse socioeconomic barriers, but they had much
      higher death rates from diabetes, chronic liver disease/cirrhosis, and homicide,
      and a higher prevalence of obesity. There were substantial differences among
      Hispanics by origin, nativity, and sex. IMPLICATIONS FOR PUBLIC HEALTH:
      Differences by origin, nativity, and sex are important considerations when
      targeting health programs to specific audiences. Increasing the proportions of
      Hispanics with health insurance and a medical home (patientcentered, team-based,
      comprehensive, coordinated health care with enhanced access) is critical. A
      feasible and systematic data collection strategy is needed to reflect health
      diversity among Hispanic origin subgroups, including by nativity.

PMID- 25950256
TI  - Living longer through mitochondrial housekeeping.

PMID- 25950255
TI  - Possible sexual transmission of Ebola virus - Liberia, 2015.
AB  - On March 20, 2015, 30 days after the most recent confirmed Ebola Virus Disease
      (Ebola) patient in Liberia was isolated, Ebola was laboratory confirmed in a
      woman in Monrovia. The investigation identified only one epidemiologic link to
      Ebola: unprotected vaginal intercourse with a survivor. Published reports from
      previous outbreaks have demonstrated Ebola survivors can continue to harbor virus
      in immunologically privileged sites for a period of time after convalescence.
      Ebola virus has been isolated from semen as long as 82 days after symptom onset
      and viral RNA has been detected in semen up to 101 days after symptom onset. One
      instance of possible sexual transmission of Ebola has been reported, although the
      accompanying evidence was inconclusive. In addition, possible sexual transmission
      of Marburg virus, a filovirus related to Ebola, was documented in 1968. This
      report describes the investigation by the Government of Liberia and international
      response partners of the source of Liberia's latest Ebola case and discusses the
      public health implications of possible sexual transmission of Ebola virus. Based
      on information gathered in this investigation, CDC now recommends that contact
      with semen from male Ebola survivors be avoided until more information regarding
      the duration and infectiousness of viral shedding in body fluids is known. If
      male survivors have sex (oral, vaginal, or anal), a condom should be used
      correctly and consistently every time. 

PMID- 25950257
TI  - Gonadal failure is associated with visceral adiposity in myotonic dystrophies.
AB  - BACKGROUND: Hypogonadism occurs in myotonic dystrophies type 1 (MD1) and type 2
      (MD2). Sertoli and Leydig cell secretions, including insulin-like peptide-3
      (INSL3), anti-Mullerian hormone (AMH) and inhibin B, were evaluated in male
      patients with MD. DESIGN: Academic settings. Forty-four male patients with MD [31
      MD1, 13 MD2, aged 59 (50-64) years, median (interquartile range)], age-, sex- and
      BMI-matched non-MD hypogonadal patients (n = 14) and healthy controls (n = 32).
      Serum FSH, LH, inhibin B, AMH, testosterone (T) and INSL3 were measured; fat and
      muscle masses were evaluated by DEXA. RESULTS: Overt primary hypogonadism
      occurred in 29% of patients with MD1 and 46% of patients with MD2. Considering
      subclinical forms, the prevalence increased to 69% of MD1 and 100% of MD2. A half
      of patients with MD experienced symptoms. INSL3 levels were unaffected in most
      patients with MD. By contrast, AMH and inhibin B were reduced in most patients
      with MD and unrelated to age. Patients with MD showed increased body and visceral
      fat. Free T levels were negatively predicted by fat mass, and AMH and FSH levels
      were negatively correlated with waist/hip ratio and fat mass. AMH, inhibin B and
      FSH levels positively correlated with muscle strength and muscle mass.
      CONCLUSIONS: AMH and inhibin B secretion failures are common in male patients
      with MD and are more severe than Leydig cell hormones impairment. AMH and inhibin
      B measurements might provide clinical utility in evaluating fertility in patients
      with MD. Serum T, AMH and inhibin B productions are negatively influenced by
      increased fat mass, while AMH and inhibin B might be markers of muscle
      impairment.

PMID- 25950258
TI  - Thrombospondin-2 Expression During Retinal Vascular Development and
      Neovascularization.
AB  - PURPOSE: To determine thrombospondin-2 (TSP2) expression and its impact on
      postnatal retinal vascular development and retinal neovascularization. METHODS:
      The TSP2-deficient (TSP2(-/-)) mice and a line of TSP2 reporter mice were used to
      assess the expression of TSP2 during postnatal retinal vascular development and
      neovascularization. The postnatal retinal vascularization was evaluated using
      immunostaining of wholemount retinas prepared at different postnatal days by
      collagen IV staining and/or TSP2 promoter driven green fluorescent protein (GFP)
      expression. The organization of astrocytes was evaluated by glial fibrillary
      acidic protein (GFAP) staining. Retinal vascular densities were determined using
      trypsin digestion preparation of wholemount retinas at 3- and 6-weeks of age.
      Retinal neovascularization was assessed during the oxygen-induced ischemic
      retinopathy (OIR). Choroidal neovascularization (CNV) was assessed using laser
      induced CNV. RESULTS: Using the TSP2-GFP reporter mice, we observed significant
      expression of TSP2 mRNA in retinas of postnatal day 5 (P5) mice, which increased
      by P7 and remained high up to P42. Similar results were observed in retinal
      wholemount preparations, and western blotting for GFP with the highest level of
      GFP was observed at P21. In contrast to high level of mRNA at P42, the GFP
      fluorescence or protein level was dramatically downregulated. The primary retinal
      vasculature developed at a faster rate in TSP2(-/-) mice compared with TSP2(+/+)
      mice up to P5. However, the developing retinal vasculature in TSP2(+/+) mice
      caught up with that of TSP2(-/-) mice after P7. No significant differences in
      retinal vascular density were observed at 3- or 6-weeks of age. TSP2(-/-) mice
      also exhibited a similar sensitivity to the hyperoxia-mediated vessel
      obliteration and similar level of neovascularization during OIR as TSP2(+/+)
      mice. Lack of TSP2 expression minimally affected laser-induced CNV compared with
      TSP2(+/+) mice. CONCLUSIONS: Lack of TSP2 expression was associated with enhanced
      retinal vascularization during early postnatal days but not at late postnatal
      times, and minimally affected retinal and CNV. However, the utility of TSP2 as a
      potential therapeutic target for inhibition of ocular neovascularization awaits
      further investigation.

PMID- 25950260
TI  - Transcranial magnetic stimulation: A potential new treatment for depression
      associated with traumatic brain injury.
AB  - BACKGROUND: Each year, more than 1.7 million Americans suffer a traumatic brain
      injury (TBI) and the lifetime prevalence of major depressive disorder following
      TBI is between 25-50%. There are no validated established strategies to treat TBI
      depression. Repetitive transcranial magnetic stimulation (rTMS) is a novel
      putative treatment option for post-TBI depression, which, compared with standard
      pharmacological agents, may provide a more targeted treatment with fewer side
      effects. However, TBI is associated with an increased risk of both early and late
      spontaneous seizures, a significant consideration in evaluating rTMS as a
      potential treatment for TBI depression. Whilst the risk of seizure from rTMS is
      low, underlying neuropathology may somewhat increase that risk. REVIEW: This
      review focuses on the safety aspects of rTMS in TBI patients. The authors review
      why low frequency rTMS might be less likely to trigger a seizure than high
      frequency rTMS and propose low frequency rTMS as a safer option in TBI patients.
      Because there is little data on the safety of rTMS in TBI, the authors also
      review the safety of rTMS in patients with other brain pathology. CONCLUSION: It
      is concluded that pilot safety and tolerability studies should be first conducted
      in persons with TBI and neuropsychiatric comorbidities. These results could be
      used to help design larger randomized controlled trials.

PMID- 25950261
TI  - Impact of BDNF Val66Met polymorphism on olfactory functions of female concussed
      athletes.
AB  - BACKGROUND: Concussions exert persistent effects on asymptomatic athletes,
      especially women. Among chief mechanisms of concussion recovery are alterations
      of neuronal plasticity. Olfactory function, often impaired following a
      concussion, greatly involves plasticity and, therefore, appears as a good
      candidate to study the deleterious effects of concussions. The BDNF Val66Met
      polymorphism (BDNFMet), which reduces availability of BDNF in the brain, has
      surprisingly been associated with better recovery following concussion.
      OBJECTIVE: This study examines the mediating effect of BDNFMet on olfactory
      functions in asymptomatic concussed female athletes. METHODS: Participants, 105
      female university athletes, were divided into four groups based on their history
      of concussion (Concussion/No concussion) and BDNF polymorphism (BDNF
      Val66Val/Val66Met). Odour threshold, discrimination and identification were
      measured using the Sniffin' Sticks Inventory Test. RESULTS: Concussed female
      BDNFMet athletes performed significantly better than BDNFVal counterparts on
      threshold (F(1, 34) = 4.73, p < 0.05), discrimination (F(1, 52) = 5.36, p <
      0.05), identification tests (F(1, 52) = 5.65, p < 0.05) and total olfactory
      scores (F(1, 34) = 9.54, p < 0.05). CONCLUSION: These results support a genotypic
      effect of the BDNF Val66Met polymorphism on long-term olfactory function
      following a concussion in young female athletes.

PMID- 25950259
TI  - Pediatric cancer epigenome and the influence of folate.
AB  - Despite improvement in clinical treatment of childhood cancer, it remains the
      leading cause of disease-related mortality in children with survivors often
      suffering from treatment-related toxicity and premature death. Because childhood
      cancer is vastly different from cancer in adults, a thorough understanding of the
      underlying molecular mechanisms specific to childhood cancer is essential.
      Although childhood cancer contains much fewer mutations, a subset of cancer
      subtypes has a higher frequency of mutations in gene encoding epigenetic
      regulators. Thus, in this review, we will focus on epigenetic deregulations in
      childhood cancers, the use of genome-wide analysis for cancer subtype
      classification, prediction of clinical outcomes and the influence of folate on
      epigenetic mechanisms. 

PMID- 25950262
TI  - Aetiologies, comorbidities and causes of death in a population of 133 patients
      with polyhandicaps cared for at specialist rehabilitation centres.
AB  - AIM: This study concerns the aetiologies, comorbidities and places and causes of
      death of a population of persons with severe polyhandicap (PLH). METHODS: Based
      on the medical files of all deceased PLH patients, who were cared for between
      2006-2012. Data collected were aetiological diagnosis of the polyhandicap,
      duration and type of hospitalization, age, place and cause of death,
      comorbidities: chronic respiratory insufficiency, recurrent attacks of pulmonary
      infections, urinary infections, active epilepsy, scoliosis, chronic digestive
      disorders and behavioural problems. RESULTS: One hundred and thirty-three
      patients died, 70 children and 63 adults. The sex ratio was 84 men to 49 women.
      The average stay in these institutions was 10 years 4 months. The average age at
      the time of death was 21 years, in 60% of cases the place of death was in the
      specialist rehabilitation centres. The causes of death in decreasing order were:
      pulmonary infections (63.2%), sudden death (18%) and status epilepticus (6.8%);
      79.7% of patients suffered from chronic respiratory insufficiency, 60.2% suffered
      serious scoliosis, 66.9% drug-resistant epilepsy and 78.9% had digestive
      disorders. The main aetiologies of the polyhandicap were: pre- and perinatal
      encephalopathies (31.6%), metabolic encephalopathies (18%) and convulsive
      encephalopathies (11.3%). CONCLUSION: The main comorbidity and main cause of
      death in patients with severe PLH is respiratory failure.

PMID- 25950263
TI  - Prevalence and predictors of affective lability after paediatric traumatic brain
      injury.
AB  - OBJECTIVE: Paediatric severe traumatic brain injury (TBI) is associated with
      significant post-injury affective and behavioural problems. Few studies have
      examined the prevalence and characteristics of affective lability after
      paediatric TBI. METHODS: Ninety-seven children with severe TBI were evaluated 1
      year post-injury for the presence of affective lability using the Children's
      Affective Lability Scale (CALS). Demographic, clinical and brain lesion
      characteristics were also assessed. RESULTS: Affective lability significantly
      increased after injury. Eighty-six children had a pre-injury CALS score of 1 SD
      or less from the group pre-injury mean (M = 8.11, SD = 9.31), of which 35 and 15
      children had a 1 SD and 2 SD increase in their CALS score from pre- to post
      injury, respectively. A variety of affective shifts manifested post-injury
      including anxiety, silliness, dysphoria and irritability. The most severe
      symptoms were irritability and unpredictable temper outbursts. Risk factors for
      affective lability included elevated pre-injury affective lability and
      psychosocial adversity as well as greater damage to the orbitofrontal cortex.
      Post-injury affective lability was most frequently associated with a post-injury
      diagnosis of attention-deficit hyperactivity disorder. CONCLUSIONS: Affective
      lability is common after paediatric TBI and frequently manifests as irritability
      and unpredictable outbursts. Early intervention is needed to improve psychiatric
      outcomes.

PMID- 25950265
TI  - Exploration of a new tool for assessing emotional inferencing after traumatic
      brain injury.
AB  - OBJECTIVE: To explore validity of an assessment tool under development-the
      Emotional Inferencing from Stories Test (EIST). This measure is being designed to
      assess the ability of people with traumatic brain injury (TBI) to make inferences
      about the emotional state of others solely from contextual cues. METHODS AND
      PROCEDURES: Study 1: 25 stories were presented to 40 healthy young adults. From
      this data, two versions of the EIST (EIST-1; EIST-2) were created. Study 2: Each
      version was administered to a group of participants with moderate-to-severe TBI
      EIST 1 group: 77 participants; EIST-2 group: 126 participants. Participants also
      completed a facial affect recognition (DANVA2-AF) test. Participants with facial
      affect recognition impairment returned 2 weeks later and were re-administered
      both tests. MAIN OUTCOMES: Participants with TBI scored significantly lower than
      the healthy group mean for EIST-1, F(1,114) = 68.49, p < 0.001, and EIST-2,
      F(1,163) = 177.39, p < 0.001. EIST scores in the EIST-2 group were significantly
      lower than the EIST-1 group, t = 4.47, p < 0.001. DANVA2-AF scores significantly
      correlated with EIST scores, EIST-1: r = 0.50, p < 0.001; EIST-2: r = 0.31, p <
      0.001. Test-re-test reliability scores for the EIST were adequate. CONCLUSIONS:
      Both versions of the EIST were found to be sensitive to deficits in emotional
      inferencing. After further development, the EIST may provide clinicians valuable
      information for intervention planning.

PMID- 25950264
TI  - Executive functions profiles in traumatic brain injury adults: Implications for
      rehabilitation studies.
AB  - PRIMARY OBJECTIVE: This study aimed to identify and characterize profiles of
      executive functions (EF) following traumatic brain injury (TBI). RESEARCH DESIGN:
      The sample was comprised of 84 adult outpatients with mild and moderate/severe
      TBI who were assessed by means of a battery of EF tasks. A Hierarchical Cluster
      analysis was performed with tasks Z-scores. Clusters were compared by means of
      ANOVA and Chi-square analyses. MAIN OUTCOMES AND RESULTS: Three clusters were
      characterized by deficits in: (1) inhibition, flexibility and focused attention;
      (2) inhibition, flexibility, working memory and focused attention; and (3) no
      expressive executive deficits. Clusters did not differ in clinical or
      demographical variables. CONCLUSIONS: The first cluster replicated findings of
      previous studies on TBI EF profiles. IT is suggested that TBI rehabilitation
      studies of EF must select participants by their EF profile rather than for
      clinical or demographical variables.

PMID- 25950266
TI  - Pilot study of traumatic brain injury and alcohol misuse among service members.
AB  - OBJECTIVE: Explore relationships among traumatic brain injury (TBI), substance
      misuse and other mental health disorders in US service members and to identify
      risk factors for substance misuse. PARTICIPANTS: Service members (n = 93 in final
      sample) injured while deployed to Operation Enduring Freedom or Operation Iraqi
      Freedom. METHODS AND MATERIALS: Longitudinal survey at 6 and 12 months post
      intake. The following measures were used: problem substance use, Alcohol
      Expectancies Questionnaire-III, MINI International Neuropsychiatric Interview
      Substance Abuse Modules, Ohio State University TBI Identification Method,
      Neurobehavioural Symptom Inventory, Rivermead Post-Concussion Symptoms
      Questionnaire, Buss-Perry Aggression Questionnaire, Post-Traumatic Stress
      Disorder Checklist-Civilian Version, Beck Depression Inventory-II, Beck Anxiety
      Inventory. RESULTS: More severe TBI and post-traumatic stress disorder (PTSD)
      symptoms at 6 months post-enrolment were associated with decreased odds of
      substance misuse 12 months after study enrolment. Alcohol expectancies and
      incurring a TBI at a younger age increased the odds of substance misuse.
      CONCLUSIONS: While the ability to generalize the current findings to a larger
      population is limited, the results provide direction for future studies on the
      prevention and treatment of substance misuse following TBI. The unexpected
      protective effect of more severe TBI may result from prospective attention to the
      injury and its consequences. Greater preventive benefit may result from
      identifying more service members with elevated risk. Lifetime history of TBI and
      alcohol expectancies may be candidate indicators for greater attention.

PMID- 25950267
TI  - Psychological problems, self-esteem and body dissatisfaction in a sample of
      adolescents with brain lesions: A comparison with a control group.
AB  - PRIMARY OBJECTIVES: This study aims to describe psychological problems, self
      esteem difficulties and body dissatisfaction in a sample of adolescents with
      acquired brain lesions and to compare them with an age- and gender-matched
      control group. RESEARCH DESIGN: In an experimental design, the psychological
      profile of 26 adolescents with brain lesions of traumatic or vascular aetiology,
      aged 12-18 years, was compared with that of 18 typically-developing subjects.
      Moreover, within the clinical group, patients with TBI were compared with
      patients with vascular lesions. METHODS AND PROCEDURES: The psychological and
      adaptive profile of the adolescents was assessed by a specific protocol,
      including CBCL, VABS, RSES, EDI-2 and BES. MAIN OUTCOME AND RESULTS: Adolescents
      with brain lesions showed more marked psychological problems than their healthy
      peers; they also presented with a greater impairment of adaptive skills and a
      lower self-esteem. No significant differences were found between patients with
      traumatic lesions and patients with vascular lesions. CONCLUSIONS: Adolescents
      with acquired brain lesions were at higher risk to develop psychological and
      behavioural difficulties. Furthermore, in the clinical sample, some variables
      such as the long hospitalization and isolation from family and peers were
      associated to a greater psychological burden than the aetiology of the brain
      damage.

PMID- 25950268
TI  - Imaging metabolism with hyperpolarized (13)C-labeled cell substrates.
AB  - Non-invasive (13)C magnetic resonance spectroscopy measurements of the uptake and
      subsequent metabolism of (13)C-labeled substrates is a powerful method for
      studying metabolic fluxes in vivo. However, the technique has been hampered by a
      lack of sensitivity, which has limited both the spatial and temporal resolution.
      The introduction of dissolution dynamic nuclear polarization in 2003, which by
      radically enhancing the nuclear spin polarization of (13)C nuclei in solution can
      increase their sensitivity to detection by more than 10(4)-fold, revolutionized
      the study of metabolism using magnetic resonance, with temporal and spatial
      resolutions in the seconds and millimeter ranges, respectively. The principal
      limitation of the technique is the short half-life of the polarization, which at
      ~20-30 s in vivo limits studies to relatively fast metabolic reactions.
      Nevertheless, pre-clinical studies with a variety of different substrates have
      demonstrated the potential of the method to provide new insights into tissue
      metabolism and have paved the way for the first clinical trial of the technique
      in prostate cancer. The technique now stands on the threshold of more general
      clinical translation. I consider here what the clinical applications might be,
      which are the substrates that most likely will be used, how will we analyze the
      resulting kinetic data, and how we might further increase the levels of
      polarization and extend polarization lifetime. 

PMID- 25950270
TI  - Graphene as an efficient interfacial layer for electrochromic devices.
AB  - This study presents an interfacial modification strategy to improve the
      performance of electrochromic films that were fabricated by a magnetron
      sputtering technique. High-quality graphene sheets, synthesized by chemical vapor
      deposition, were used to modify fluorine-doped tin oxide substrates, followed by
      the deposition of high-performance nanocomposite nickel oxide electrochromic
      films. Electrochromic cycling results revealed that a near-complete monolayer
      graphene interfacial layer improves the electrochromic performance in terms of
      switching kinetics, activation period, coloration efficiency, and bleached-state
      transparency, while maintaining ~100% charge reversibility. The present study
      offers an alternative route for improving the interfacial properties between
      electrochromic and transparent conducting oxide films without relying on
      conventional methods such as nanostructuring or thin film composition control.

PMID- 25950269
TI  - Persistence of Ebola Virus in Ocular Fluid during Convalescence.
AB  - Among the survivors of Ebola virus disease (EVD), complications that include
      uveitis can develop during convalescence, although the incidence and pathogenesis
      of EVD-associated uveitis are unknown. We describe a patient who recovered from
      EVD and was subsequently found to have severe unilateral uveitis during
      convalescence. Viable Zaire ebolavirus (EBOV) was detected in aqueous humor 14
      weeks after the onset of EVD and 9 weeks after the clearance of viremia. 

PMID- 25950271
TI  - Fabrication and kinetics study of nano-Al/NiO thermite film by electrophoretic
      deposition.
AB  - Nano-Al/NiO thermites were successfully prepared as film by electrophoretic
      deposition (EPD). For the key issue of this EPD, a mixture solvent of ethanol
      acetylacetone (1:1 in volume) containing 0.00025 M nitric acid was proved to be a
      suitable dispersion system for EPD. The kinetics of electrophoretic deposition
      for both nano-Al and nano-NiO were investigated; the linear relation between
      deposition weight and deposition time in short time and parabolic relation in
      prolonged time were observed in both EPDs. The critical transition time between
      linear deposition kinetics and parabolic deposition kinetics for nano-Al and nano
      NiO were 20 and 10 min, respectively. The theoretical calculation of the kinetics
      of electrophoretic deposition revealed that the equivalence ratio of nano-Al/NiO
      thermites film would be affected by the behavior of electrophoretic deposition
      for nano-Al and nano-NiO. The equivalence ratio remained steady when the linear
      deposition kinetics dominated for both nano-Al and nano-NiO. The equivalence
      ratio would change with deposition time when deposition kinetics for nano-NiO
      changed into parabolic kinetics dominated after 10 min. Therefore, the rule was
      suggested to be suitable for other EPD of bicomposites. We also studied
      thermodynamic properties of electrophoretic nano-Al/NiO thermites film as well as
      combustion performance. 

PMID- 25950272
TI  - Phase-vanishing method with acetylene evolution and its utilization in several
      organic syntheses.
AB  - A novel quadraphasic phase-vanishing system in which acetylene is evolved from
      calcium carbide and directly applied in situ to the Sonogashira coupling reaction
      was developed. This method, which provides a safe, convenient, and one-pot means
      to utilize gaseous reagents without special equipment, was also applied to a Cu
      catalyzed azide-alkyne cycloaddition (CuAAC) reaction and a three-component
      aldehyde-alkyne-amine (A(3)) coupling reaction with excellent results. 

PMID- 25950274
TI  - Unimolecular electronics.

PMID- 25950273
TI  - Evaluation of an In Situ Gelable and Injectable Hydrogel Treatment to Preserve
      Human Disc Mechanical Function Undergoing Physiologic Cyclic Loading Followed by
      Hydrated Recovery.
AB  - Despite the prevalence of disc degeneration and its contributions to low back
      problems, many current treatments are palliative only and ultimately fail. To
      address this, nucleus pulposus replacements are under development. Previous work
      on an injectable hydrogel nucleus pulposus replacement composed of n-carboxyethyl
      chitosan, oxidized dextran, and teleostean has shown that it has properties
      similar to native nucleus pulposus, can restore compressive range of motion in
      ovine discs, is biocompatible, and promotes cell proliferation. The objective of
      this study was to determine if the hydrogel implant will be contained and if it
      will restore mechanics in human discs undergoing physiologic cyclic compressive
      loading. Fourteen human lumbar spine segments were tested using physiologic
      cyclic compressive loading while intact, following nucleotomy, and again
      following treatment of injecting either phosphate buffered saline (PBS) (sham, n
      = 7) or hydrogel (implant, n = 7). In each compressive test, mechanical
      parameters were measured immediately before and after 10,000 cycles of
      compressive loading and following a period of hydrated recovery. The hydrogel
      implant was not ejected from the disc during 10,000 cycles of physiological
      compression testing and appeared undamaged when discs were bisected following all
      mechanical tests. For sham samples, creep during cyclic loading increased (+15%)
      from creep during nucleotomy testing, while for implant samples creep strain
      decreased (-3%) toward normal. There was no difference in compressive modulus or
      compressive strains between implant and sham samples. These findings demonstrate
      that the implant interdigitates with the nucleus pulposus, preventing its
      expulsion during 10,000 cycles of compressive loading and preserves disc creep
      within human L5-S1 discs. This and previous studies provide a solid foundation
      for continuing to evaluate the efficacy of the hydrogel implant.

PMID- 25950275
TI  - Differential photoactivity of aqueous [C60] and [C70] fullerene aggregates.
AB  - Many past studies have focused on the aqueous photochemical properties of
      colloidal suspensions of C60 and various [C60] fullerene derivatives, yet few
      have investigated the photochemistry of other larger cage fullerene species
      (e.g., C70, C74, C84, etc.) in water. This is a critical knowledge gap because
      these larger fullerenes may exhibit different properties compared to C60,
      including increased visible light absorption, altered energy level structures,
      and variable cage geometries, which may greatly affect aggregate properties and
      resulting aqueous photoactivity. Herein, we take the first steps toward a
      detailed investigation of the aqueous photochemistry of larger cage fullerene
      species, by focusing on [C70] fullerene. We find that aqueous suspensions of C60
      and C70, nC60 and nC70, respectively, exhibit many similar physicochemical
      properties, yet nC70 appears to be significantly more photoactive than nC60.
      Studies are conducted to elucidate the mechanism behind nC70's superior (1)O2
      generation, including the measurement of (1)O2 production as a function of
      incident excitation wavelength, analysis of X-ray diffraction data to determine
      crystal packing arrangements, and the excited state dynamics of aggregate
      fullerene species via transient absorption spectroscopy. 

PMID- 25950276
TI  - Determinants of underdiagnosis of COPD in national and international surveys.
AB  - BACKGROUND: COPD ranks within the top three causes of mortality in the global
      burden of disease, yet it remains largely underdiagnosed. We assessed the
      underdiagnosis of COPD and its determinants in national and international surveys
      of general populations. METHODS: We analyzed representative samples of adults
      aged >= 40 years randomly selected from well-defined administrative areas
      worldwide (44 sites from 27 countries). Postbronchodilator FEV1/FVC < lower limit
      of normal (LLN) was used to define chronic airflow limitation consistent with
      COPD. Undiagnosed COPD was considered when participants had postbronchodilator
      FEV1/FVC < LLN but were not given a diagnosis of COPD. RESULTS: Among 30,874
      participants with a mean age of 56 years, 55.8% were women, and 22.9% were
      current smokers. Population prevalence of (spirometrically defined) COPD ranged
      from 3.6% in Barranquilla, Colombia, to 19.0% in Cape Town, South Africa. Only
      26.4% reported a previous lung function test, and only 5.0% reported a previous
      diagnosis of COPD, whereas 9.7% had a postbronchodilator FEV1/FVC < LLN. Overall,
      81.4% of (spirometrically defined) COPD cases were undiagnosed, with the highest
      rate in Ile-Ife, Nigeria (98.3%) and the lowest rate in Lexington, Kentucky
      (50.0%). In multivariate analysis, a greater probability of underdiagnosis of
      COPD was associated with male sex, younger age, never and current smoking, lower
      education, no previous spirometry, and less severe airflow limitation.
      CONCLUSIONS: Even with substantial heterogeneity in COPD prevalence, COPD
      underdiagnosis is universally high. Because effective management strategies are
      available for COPD, spirometry can help in the diagnosis of COPD at a stage when
      treatment will lead to better outcomes and improved quality of life.

PMID- 25950277
TI  - Contemplating the Diagnostic Certainty of Primary Iris Mucosa-Associated Lymphoid
      Tissue Lymphoma-Reply.

PMID- 25950278
TI  - The etiology of Rubella IgM positivity in patients with rubella-like illness in
      Iran from 2011 to 2013.
AB  - Rubella is a mild self-limiting contagious viral disease caused by the rubella
      virus (RV). Although symptoms are often mild, the concern is centralized around
      the possible effect on a fetus growth and development in case of primary
      infection during early months of pregnancy. Recently acquired rubella is commonly
      confirmed by RV-specific IgM antibody detection in the serum. However, rubella
      primary infection is not always the only cause of IgM positivity. Other possible
      causes of rubella IgM positivity may include IgM persistence following
      vaccination or naturally acquired infection or even re-infection. Moreover,
      nonspecific IgM reactivity can cause false-positive results. There are few
      articles to differentiate the aetiology of rash in rubella-like illnesses.
      However, limited studies have been conducted on clarifying the source of IgM
      positivity in these cases. This article reports the study of 10,896 clinical
      cases demonstrating rubella-like illness between 2011 and 2013 in Iran. The rate
      of IgM positivity among these cases was 0.52% (57 cases). As predicted based on
      the high coverage of vaccination in Iran fewer than 16% of cases with ELISA IgM
      positive result, were due to current rubella primary infections. The greater part
      of the positive IgM reactions occurred in cross reactivity with other viruses
      (31.6%) or in prolonged IgM response post vaccination (24.6%). This research
      confirmed that the positive result of rubella IgM assay in vaccinated individuals
      is mainly caused by prolonged IgM production, rubella re-infection, and false
      positivity due to infection with other viruses, rather than the rubella primary
      infection itself.

PMID- 25950280
TI  - An adipogenic gel for surgical reconstruction of the subcutaneous fat layer in a
      rat model.
AB  - 'Off-the-shelf' tissue-engineered skin alternatives for epidermal and dermal skin
      layers are available; however, no such alternative for the subdermal fat layer
      exists. Without this well-vascularized layer, skin graft take is variable and
      grafts may have reduced mobility, contracture and contour defects. In this study
      a novel adipose-derived acellular matrix (Adipogel) was investigated for its
      properties to generate subdermal fat in a rat model. In a dorsal thoracic site, a
      1 * 1 cm Adipogel implant was inserted within a subdermal fat layer defect. In a
      dorsal lumbar site, an Adipogel implant was inserted in a subfascial pocket.
      Contralateral control defects remained empty. At 8 weeks wound/implant sites were
      evaluated histologically, immunohistochemically and morphometrically.
      Identifiable thoracic Adipogel implants lost volume in vivo over 8 weeks.
      Neovascularization and adipogenesis were evident within implants and adipocyte
      percentage volume was 33.07 +/- 6.55% (mean +/- SEM). A comparison of entire
      cross-sections of thoracic wounds demonstrated a significant increase in total
      wound fat in Adipogel-implanted wounds (37.19 +/- 4.48%, mean +/- SEM) compared
      to control (16.53 +/- 4.60%; p = 0.0092), indicating that some Adipogel had been
      completely converted to normal fat. At the lumbar site, Adipogel also lost
      volume, appearing flattened, although fat generation and angiogenesis occurred.
      At both sites macrophage infiltration was mild, whilst many infiltrating cells
      were PDGFRbeta-positive mesenchymal cells. Adipogel is adipogenic and angiogenic
      and is a promising candidate for subcutaneous fat regeneration; it has the
      potential to be a valuable adjunct to wound-healing therapy and reconstructive
      surgery practice. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 25950281
TI  - 2014 ISSLS Presidential Address.

PMID- 25950279
TI  - Fast rotary nonlinear spatial acquisition (FRONSAC) imaging.
AB  - PURPOSE: Nonlinear spatial encoding magnetic fields (SEMs) have been studied to
      reconstruct images from a minimum number of echoes. Previous work has also
      explored single shot trajectories in nonlinear SEMs. However, the search
      continues for optimal schemes that apply nonlinear SEMs to improve spatial
      encoding efficiency and image quality. THEORY AND METHODS: We enhance the
      encoding efficiency of standard linear gradient trajectories by adding a rapidly
      rotating nonlinear SEM of moderate amplitude, the so called FRONSAC (Fast ROtary
      Nonlinear Spatial ACquisition) imaging. This additional gradient greatly improves
      the image quality of highly undersampled single-shot trajectories, including EPI,
      Spiral, and Rosette trajectories. RESULTS: Our simulations, including noise and
      dephasing effects, test the effect of adding FRONSAC gradients, demonstrating the
      applicability of this approach. Performance is explained by demonstrating the
      additional k-space sampling the nonlinear gradient provides. Studies of the
      optimal amplitude and frequency of the additional FRONSAC field are presented,
      and the role of enhanced sampling during the readout demonstrated. Dynamic field
      mapping in a second-order gradient system shows the proposed gradient waveforms
      are feasible. CONCLUSION: Images resulting from highly undersampled existing k
      space trajectories, such as EPI, Spiral, and Rosette, are greatly enhanced simply
      by adding a rotating nonlinear SEM field.

PMID- 25950284
TI  - Chiral Selective Chemistry Induced by Natural Selection of Spin-Polarized
      Electrons.
AB  - The search to understand the origin of homochirality in nature has been ongoing
      since the time of Pasteur. Previous work has shown that DNA can act as a spin
      filter for low-energy electrons and that spin-polarized secondary electrons
      produced by X-ray irradiation of a magnetic substrate can induce chiral selective
      chemistry. In the present work it is demonstrated that secondary electrons from a
      substrate that are transmitted through a chiral overlayer cause enantiomeric
      selective chemistry in an adsorbed adlayer. We determine the quantum yields (QYs)
      for dissociation of (R)- or (S)-epichlorohydrin adsorbed on a chiral self
      assembled layer of DNA on gold and on bare gold (for control). The results show
      that there is a significant difference in the QYs between the two enantiomers
      when adsorbed on DNA, but none when they are adsorbed on bare Au. We propose that
      the effect results from natural spin filtering effects cause by the chiral
      monolayer. 

PMID- 25950282
TI  - Cost-utility of cognitive behavioral therapy for low back pain from the
      commercial payer perspective.
AB  - STUDY DESIGN: Markov cost-utility model. OBJECTIVE: To evaluate the cost-utility
      of cognitive behavioral therapy (CBT) for the treatment of persistent nonspecific
      low back pain (LBP) from the perspective of US commercial payers. SUMMARY OF
      BACKGROUND DATA: CBT is widely deemed clinically effective for LBP treatment. The
      evidence is suggestive of cost-effectiveness. METHODS: We constructed and
      validated a Markov intention-to-treat model to estimate the cost-utility of CBT,
      with 1-year and 10-year time horizons. We applied likelihood of improvement and
      utilities from a randomized controlled trial assessing CBT to treat LBP. The
      trial randomized subjects to treatment but subjects freely sought health care
      services. We derived the cost of equivalent rates and types of services from US
      commercial claims for LBP for a similar population. For the 10-year estimates, we
      derived recurrence rates from the literature. The base case included medical and
      pharmaceutical services and assumed gradual loss of skill in applying CBT
      techniques. Sensitivity analyses assessed the distribution of service
      utilization, utility values, and rate of LBP recurrence. We compared health plan
      designs. Results are based on 5000 iterations of each model and expressed as an
      incremental cost per quality-adjusted life-year. RESULTS: The incremental cost
      utility of CBT was $7197 per quality-adjusted life-year in the first year and
      $5855 per quality-adjusted life-year over 10 years. The results are robust across
      numerous sensitivity analyses. No change of parameter estimate resulted in a
      difference of more than 7% from the base case for either time horizon. Including
      chiropractic and/or acupuncture care did not substantively affect cost
      effectiveness. The model with medical but no pharmaceutical costs was more cost
      effective ($5238 for 1 yr and $3849 for 10 yr). CONCLUSION: CBT is a cost
      effective approach to manage chronic LBP among commercial health plans members.
      Cost-effectiveness is demonstrated for multiple plan designs. LEVEL OF EVIDENCE:
      2.

PMID- 25950285
TI  - Mechanochemical Rhodium(III)-Catalyzed C-H Bond Functionalization of Acetanilides
      under Solventless Conditions in a Ball Mill.
AB  - In a proof-of-principle study, a planetary ball mill was applied to rhodium(III)
      catalyzed C-H bond functionalization. Under solventless conditions and in the
      presence of a minute amount of Cu(OAc)2, the mechanochemical activation led to
      the formation of an active rhodium species, thus enabling an oxidative Heck-type
      cross-coupling reaction with dioxygen as the terminal oxidant. The absence of an
      organic solvent, the avoidance of a high reaction temperature, the possibility of
      minimizing the amount of the metallic mediator, and the simplicity of the
      protocol result in a powerful and environmentally benign alternative to the
      common solution-based standard protocol.

PMID- 25950287
TI  - Polyfunctional Lewis acids: intriguing solid-state structure and selective
      detection and discrimination of nitroaromatic explosives.
AB  - Synthesis and crystal structures of three porphyrin-based polyfunctional Lewis
      acids 1-3 are reported. Intermolecular HgCl???HgCl (linear and MU-type)
      interactions in the solid state of the peripherally ArHgCl-decorated compound 3
      lead to a fascinating 3D supramolecular architecture. Compound 3 shows a
      selective fluorescence quenching response to picric acid and discriminates other
      nitroaromatic-based explosives. For the first time, an electron-deficient
      polyfunctional Lewis acid is shown to be useful for the selective detection and
      discrimination of nitroaromatic explosives. The Stern-Volmer quenching constant
      and detection limits of compound 3 for picric acid are the best among the
      reported small-molecular receptors for nitroaromatic explosives. The electronic
      structure, Lewis acidity, and selective sensing characteristics of 3 are well
      corroborated by DFT calculations. 

PMID- 25950288
TI  - Aberrant cerebral network topology and mild cognitive impairment in early
      Parkinson's disease.
AB  - The aim of this study was to assess whether mild cognitive impairment (MCI) is
      associated with disruption in large-scale structural networks in newly diagnosed,
      drug-naive patients with Parkinson's disease (PD). Graph theoretical analyses
      were applied to 3T MRI data from 123 PD patients and 56 controls from the
      Parkinson's progression markers initiative (PPMI). Thirty-three patients were
      classified as having Parkinson's disease with mild cognitive impairment (PD-MCI)
      using the Movement Disorders Society Task Force criteria, while the remaining 90
      PD patients were classified as cognitively normal (PD-CN). Global measures
      (clustering coefficient, characteristic path length, global efficiency, small
      worldness) and regional measures (regional clustering coefficient, regional
      efficiency, hubs) were assessed in the structural networks that were constructed
      based on cortical thickness and subcortical volume data. PD-MCI patients showed a
      marked reduction in the average correlation strength between cortical and
      subcortical regions compared with controls. These patients had a larger
      characteristic path length and reduced global efficiency in addition to a lower
      regional efficiency in frontal and parietal regions compared with PD-CN patients
      and controls. A reorganization of the highly connected regions in the network was
      observed in both groups of patients. This study shows that the earliest stages of
      cognitive decline in PD are associated with a disruption in the large-scale
      coordination of the brain network and with a decrease of the efficiency of
      parallel information processing. These changes are likely to signal further
      cognitive decline and provide support to the role of aberrant network topology in
      cognitive impairment in patients with early PD.

PMID- 25950286
TI  - Pneumatic retinopexy versus scleral buckle for repairing simple rhegmatogenous
      retinal detachments.
AB  - BACKGROUND: Rhegmatogenous retinal detachment (RRD) is a full-thickness break in
      the sensory retina, caused by vitreous traction on the retina. While pneumatic
      retinopexy, scleral buckle, and vitrectomy are the accepted surgical
      interventions for eyes with RRD, their relative effectiveness has remained
      controversial.  OBJECTIVES: The objectives of this review were to assess the
      effectiveness and safety of pneumatic retinopexy versus scleral buckle or
      pneumatic retinopexy versus a combination treatment of scleral buckle and
      vitrectomy for people with RRD. The secondary objectives were to summarize any
      data on economic measures and quality of life. SEARCH METHODS: We searched
      CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register)
      (2014, Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed
      Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to January 2015),
      EMBASE (January 1980 to January 2015), Latin American and Caribbean Health
      Sciences Literature Database (LILACS) (January 1982 to January 2015), the ISRCTN
      registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov
      (www.clinicaltrials.gov) and the World Health Organization (WHO) International
      Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did
      not use any date or language restrictions in the electronic searches for trials.
      We last searched the electronic databases on 13 January 2015. SELECTION CRITERIA:
      We included all randomized or quasi-randomized controlled trials comparing the
      effectiveness of pneumatic retinopexy versus scleral buckle (with or without
      vitrectomy) for eyes with RRD. DATA COLLECTION AND ANALYSIS: After screening for
      eligibility, two review authors independently extracted study characteristics,
      methods, and outcomes. We followed systematic review standards as set forth by
      The Cochrane Collaboration. MAIN RESULTS: We included two randomized controlled
      trials (218 eyes of 216 participants) comparing the effectiveness of pneumatic
      retinopexy versus scleral buckle for eyes with RRD. We identified no studies
      investigating the comparison of pneumatic retinopexy versus a combination
      treatment of scleral buckle and vitrectomy. Of the two included studies, one was
      a small study with 20 participants enrolled in Ireland and followed for an
      average of 16 months. The second study was larger with 196 participants (198
      eyes) enrolled in the United States and followed for at least 6 months. Cautious
      interpretation of the results is warranted, since we graded the evidence as low
      to moderate quality due to insufficient reporting of study methods and
      imprecision and inconsistency among study results.Both studies showed fewer eyes
      achieving retinal reattachment in the pneumatic retinopexy group compared with
      the scleral buckle group by six-months follow-up (risk ratio (RR) 0.89, 95%
      confidence interval (CI) 0.77 to 1.02, 218 eyes); however, we are uncertain as to
      whether the intervention has an important effect on reattachment because the
      results are imprecise. Eyes in the pneumatic retinopexy group also were more
      likely to have had a recurrence of retinal detachment by six-months follow-up (RR
      1.80, 95% CI 1.00 to 3.24, 218 eyes); however, we are uncertain as to whether the
      intervention has an important effect on recurrence because the lower CI equals no
      difference. Neither study reported mean change in visual acuity, quality of life
      data, or economic measures. Differences between the pneumatic retinopexy group
      and scleral buckle group were uncertain due to small numbers of events with
      respect to operative ocular adverse events (RR 0.67, 95% CI 0.32 to 1.42, 218
      eyes), development of cataract (RR 0.92, 95% CI 0.06 to 14.54, 198 eyes),
      glaucoma (RR 0.31, 95% CI 0.03 to 2.91, 198 eyes), macular pucker (RR 0.74, 95%
      CI 0.20 to 2.67, 198 eyes), and proliferative vitreoretinopathy (RR 0.94, 95% CI
      0.30 to 2.96, 218 eyes). Fewer eyes in the pneumatic retinopexy group compared
      with the scleral buckle group experienced choroidal detachment (RR 0.17, 95% CI
      0.05 to 0.57, 198 eyes) or myopic shift equal to or greater than 1 diopter
      spherical equivalent (RR 0.04, 95% CI 0.01 to 0.13, 198 eyes). AUTHORS'
      CONCLUSIONS: The evidence suggests that pneumatic retinopexy may result in lower
      rates of reattachment and higher rates of recurrence than scleral buckle for eyes
      with RRD, but does not rule out no difference between procedures. The relative
      safety of the procedures is uncertain and the relative effects of these
      procedures in terms of other patient-important outcomes, such as visual acuity
      and quality of life, is unknown. Due to the limited information available between
      pneumatic retinopexy and scleral buckle procedures, future research addressing
      these evidence gaps are warranted.

PMID- 25950289
TI  - SCAI core curriculum for adult and pediatric interventional fellowship training
      in continuous quality assessment and improvement.

PMID- 25950291
TI  - The river, the sisters, and the war.

PMID- 25950290
TI  - Use of Intra-arterial Thrombolytic Therapy for Acute Treatment of Frostbite in 62
      Patients with Review of Thrombolytic Therapy in Frostbite.
AB  - Amputations are common after severe frostbite injuries, often mediated by
      postinjury arterial thrombosis. Since 1994, the authors have performed
      angiography to identify perfusion deficits in severely frostbitten digits and
      treated these lesions with intraarterial infusion of thrombolytic agents, usually
      combined with papaverine to reduce vasospasm. A retrospective review was
      performed of patients admitted to the regional burn center with frostbite injury
      from 1994 to 2007. Patients with severe frostbite, without contraindications to
      thrombolytic therapy, underwent diagnostic angiography of the affected
      extremities. Limbs with perfusion defects received intraarterial thrombolytic
      therapy according to protocol and the response was documented. Delayed amputation
      was performed for mummified digits. Angiogram results and amputation rates were
      tabulated. In this 14-year review, 114 patients were admitted for frostbite
      injuries. There was a male predominance (84%) and the mean age was 40.4 years. Of
      this group, 69 patients with severe frostbite underwent angiography; 66 were
      treated with intraarterial thrombolytic therapy. Four treated were excluded due
      to incomplete data. In the remaining 62 patients, angiography identified 472
      digits with frostbite injury and impaired arterial perfusion. At the termination
      of thrombolytic infusion, a completion angiogram was performed. Partial or
      complete amputations were performed on only four of 198 digits (2.0%) with distal
      vascular blush, and in 71 of 75 digits (94.7%) with no improvement. Amputations
      occurred in 73 of 199 digits (36.7%) with partially restored flow. Overall
      complete digit salvage rate was 68.6%. Angiography after severe frostbite is a
      sensitive method to detect impaired arterial blood flow and permits catheter
      directed treatment with thrombolytic agents. Improved perfusion after such
      treatment decreases late amputations following frostbite injury.

PMID- 25950292
TI  - The potential value of preoperative cytobrush papanicolaou smear in clinical
      stage I endometrial carcinoma.
AB  - PURPOSE: Our purpose was to assess the value of preoperative cytobrush
      Papanicolaou (Pap) smear in patients with uterine cancer clinically confined to
      the uterine corpus (stage I by previous International Federation of Gynecology
      and Obstetrics classification). METHODS AND MATERIALS: Over a 6-year period, 300
      consecutive women with clinical stage I endometrial cancer were evaluated
      prospectively by preoperative Cytobrush (Unimar Products, Shelton, CT) Pap
      smears. RESULTS: A total of 246 patients (82%) had normal preoperative Pap
      smears. The diagnosis of either adenocarcinoma (24 patients; 8.0%) or atypical
      glandular cells of undetermined significance (30 patients; 10%) usually was
      associated with subclinical advanced surgical-stage disease or with the presence
      of high-risk subtypes, such as clear-cell carcinoma or papillary serous
      carcinoma. CONCLUSION: Abnormal preoperative cytobrush Pap smear in clinical
      stage I endometrial cancer should alert clinicians to the possibility of
      unsuspected occult metastatic disease or the presence of high-risk histological
      subtypes and should be taken into account in surgical treatment planning.

PMID- 25950293
TI  - A classification of vulvoscopic findings for clinical diagnosis.
AB  - OBJECTIVES: We describe vulvoscopic findings, their correspondence with certain
      pathological processes, and the grouping of vulvoscopic findings to facilitate
      clinical practice. MATERIALS AND METHODS: We performed vulvoscopy on 2,352
      patients and described what we saw. We then classified the images by groups,
      according to the diagnoses suggested. Finally, we compared the frequency of the
      different images as a function of the symptoms, the clinical and histological
      diagnoses, the history of cervical lesions (cervical human papillomavirus,
      cervical intraepithelial neoplasia, or cervical carcinoma), and the
      microbiological studies. RESULTS: We found 2.33% human papillomavirus-vulvar
      intraepithelial neoplasia (HPV-VIN) type 1 lesions, 0.52% herpes simplex lesions,
      and 0.08% VIN2 lesions in asymptomatic patients without a history of cervical
      lesions. In 95% of patients in whom raised acetowhite patches were found on the
      skin, vaginal exudate revealed Candida species. The images showing cobbled mucosa
      and white and red punctation primarily suggested a nonviral infection, though a
      small percentage of cases were of viral origin. The history of cervical lesions
      was significant (p < .000001) in the HPV-VIN1 lesion group. For the diagnosis of
      more severe vulvar lesions (VIN3 and vulvar carcinoma), we found that the joint
      presence of pruritus and a history of cervical lesions was significant (p <
      .004). CONCLUSIONS: Vulvoscopy performed as a routine examination procedure
      enables the detection of some disorders in asymptomatic patients who lack a
      history of cervical lesions and precludes the need for histological studies in
      some cases, though in others the image is inconclusive and a biopsy is required.
      Given that a description of normal findings is available, we are able to
      eliminate suspect pathological processes through a vulvoscopic examination. The
      proposed classification can serve as a guide to diagnosis and therapy.

PMID- 25950294
TI  - Bipolar electrosurgical loop excision procedure for cervical intraepithelial
      neoplasia.
AB  - OBJECTIVES: We sought to determine the safety and efficacy of a bipolar
      electrosurgical loop excision instrument in the diagnosis and treatment of
      cervical intraepithelial neoplasia (CIN). MATERIALS AND METHODS: Twenty-eight
      patients underwent treatment for CIN using a 20 x 10-mm bipolar electrosurgical
      loop device (Valley Forge Scientific, Oaks, PA). A Malis (Valley Forge
      Scientific) electrosurgical generator unit (60 watts cutting) was used to remove
      the cervical lesion and transformation zone under colposcopic guidance. Specimens
      were evaluated for histopathological diagnosis, tissue depth, fragmentation of
      specimens, mean maximal thermal artifact, and mean maximal endocervical and
      ectocervical thermal artifact. RESULTS: Final pathology from bipolar
      electrosurgical loop excision revealed CIN3 (8), CIN2 (4), CIN1 (11), human
      papillomavirus changes (3), and normal findings (2). Mean operating time was less
      than 15 minutes, and mean estimated blood loss was less than 10 ml. Average
      number of tissue pieces was 1.6 (range, 1-4). No complications occurred. Mean
      maximal thermal artifact was 0.318 mm. Mean endocervical mucosal and ectocervical
      mucosal thermal artifacts were 0.177 mm and 0.176 mm, respectively. Mean tissue
      depth of the excised specimen was 0.40 cm. Histopathological diagnosis was
      possible on all specimens. In five specimens (17.9%), evaluation of the
      cauterized endocervical margin for CIN was not possible, owing to thermal
      artifact. No correlation was observed between tissue depth and thermal artifact.
      CONCLUSION: Bipolar electrosurgical loop excision for the treatment of CIN is a
      safe and effective alternative to the traditional unipolar electrosurgical loop
      excision. Thermal artifact did not interfere with histopathological diagnosis,
      and the presence of artifact at cauterized margins was similar to that reported
      for historically unipolar specimens. A randomized control trial comparing
      therapeutic effectiveness of bipolar electrosurgical loop excision and unipolar
      electrosurgical loop excision is planned.

PMID- 25950295
TI  - Development of a population survey concerning papanicolaou smear screening for
      cervical disease.
AB  - OBJECTIVES: We set out to design and evaluate a questionnaire for determining
      women's knowledge, attitudes, behaviors, and experience with cervical screening.
      METHODS: A literature search was conducted using key terms such as Pap
      (Papanicolaou) smear and attitudes. No questionnaire in the literature addressed
      all the domains of knowledge, attitudes, behavior, and experience. The expert
      panel method was employed, by which eight women representing the general public,
      experts in cervical disease, or experts in questionnaire design developed a pool
      of questions. Item reduction was accomplished by consensual agreement and
      pretesting. The questionnaire was pilot-tested for acceptability, feasibility,
      comprehension, test-retest reliability, and face and content validity. RESULTS:
      Fifty-one women completed the questionnaire. The mean age was 42 +/- 13 years. Of
      these respondents, 43% were college-educated and 28% each had a high school or
      university education. All women were parous (10% had one child, 31% had two, 18%
      had three, 33% had four, and 8% had five children). The questionnaire was
      completed on two occasions. Test-retest reliability was assessed using Cohen's
      kappa statistic, Wilcoxon's test, Kendall's tau-b, or Pearson's correlation
      coefficient. These were statistically significant at p < .05 for 13 of 24 of the
      knowledge questions, 24 of 30 experience questions, 16 of 20 attitude questions,
      all behavior questions, and 3 of 4 registry questions. Some questions could not
      be evaluated because of a lack of variance. Internal consistency was computed
      using Cronbach's alpha: registry (0.9), experience (0.7), knowledge (0.6), and
      attitude (0.2). External validity was assessed by comparing the date of a woman's
      last Pap smear as reported by the woman with that recorded on the physician's
      record. The questionnaire was rated as easily understandable by 90% of
      respondents and was rated as "acceptable" by 95%. Women were very knowledgeable
      about the purpose of Pap smears (98%) and were reasonably knowledgeable about who
      needs such smears (>85%). In the domain of knowledge, four questions addressed
      risk factors for cervical disease. In general, these questions were answered with
      poor accuracy (range, 37%-60%). Women believed that the experience of having a
      Pap smear would be improved if the staff knocked before entering the room (87%),
      a warm speculum was used (86%) and the physician explained the procedure (75%).
      Eightyeight percent were willing to participate in a cervical screening registry.
      CONCLUSION: The psychometric properties of this questionnaire have been
      described. Two of the attitudinal questions were poorly understood by the
      respondents, and the items within the questions did not appear to address a
      single concept (low internal validity). Health care professionals could take
      simple measures to ensure that the experience of having a Pap smear is more
      agreeable.

PMID- 25950296
TI  - Clinical significance of histiocytes found on cervical cytology.
AB  - OBJECTIVE: Our aim was to determine the incidence of cervical and endometrial
      pathology associated with the diagnosis of histiocytes on cervical cytology.
      MATERIALS AND METHODS: A retrospective review was conducted from 1993 to 1995 of
      cervical cytology reports in which histiocytes were named in the descriptive
      diagnosis. Charts were reviewed and follow-up was performed on all patients for
      an additional 2 years. RESULTS: Histiocytes were diagnosed in 226 of 82,018
      (0.27%) cytology reports. Histiocytes alone (110), histiocytes and endometrial
      cells (40), and histiocytes and inflammation (45) were reported in the patients
      with complete follow-up. Final pathological findings after 2 years of follow-up
      were normal in 169 cases; other findings included polyps (6), simple hyperplasia
      (10), complex hyperplasia (1), previously treated cervical cancer (4), and
      endometrial cancer (5). All patients with endometrial cancer had clinical signs
      and symptoms of disease. CONCLUSION: The diagnosis of histiocytes on cervical
      cytology is associated with neoplasia (7.8%) or cancer (2.6%) in some cases.
      However, significant neoplasia (i.e., carcinoma or atypical hyperplasia) was
      associated with clinical signs and symptoms. On cytological workup, the finding
      of histiocytes in the absence of symptoms appears not to be associated with
      significant pathology.

PMID- 25950298
TI  - George C . Trombetta, MD, teaching award.

PMID- 25950297
TI  - Best overall paper.

PMID- 25950299
TI  - Preclinical Feasibility Study of Nuclear Matrix Protein CvC-3 in Detecting
      Cervical Dysplasia.

PMID- 25950300
TI  - The significance of finding trichomonas on papanicolaou smears.

PMID- 25950302
TI  - Amitriptyline versus placebo for treatment of vulvodynia: a prospective study.

PMID- 25950301
TI  - CO2 Laser Excision for High-Grade Vulvar Intraepithelial Neoplasia.

PMID- 25950303
TI  - Papillary lesions of the anal canal.

PMID- 25950304
TI  - Incidence of Vaginal Lesions with HPV Lesions at Other Sites.

PMID- 25950305
TI  - Correlation of the Digene HPV Assay Hybrid Capture System with Colposcopically
      Guided Biopsy Results.

PMID- 25950306
TI  - Sutureless technique for cold-knife conization: a report of seventy-four
      consecutive cases.

PMID- 25950307
TI  - Comparison of Endocervical Curettage (ECC) and Endocervical Brush (ECB) in
      Predicting Endocervical Pathology: Should ECB Replace ECC?

PMID- 25950308
TI  - Incidence and predictors of cervical dysplasia in patients with minimally
      abnormal pap smears.

PMID- 25950309
TI  - Poor cytohistopathological correlation in a bethesda system-based colposcopic
      triage system: clinical significance.

PMID- 25950310
TI  - Effectiveness of a midlevel provider in performing colposcopy and treating women
      with abnormal papanicolaou smears.

PMID- 25950311
TI  - Intramucosal block to alleviate pain and cramping associated with cryosurgery.

PMID- 25950312
TI  - Follow-up for abnormal papanicolaou smears in a high-risk population.

PMID- 25950313
TI  - Invasive cervical cancer in members of a prepaid health plan: the effect of
      menopausal status on disease characteristics.

PMID- 25950314
TI  - Relationship between erythrocyte folate levels and cervical intraepithelial
      neoplasia and human papillomavirus infection.

PMID- 25950315
TI  - Cytology specimen adequacy using different papanicolaou smear techniques.

PMID- 25950317
TI  - Evaluation of Cone Biopsy Margins of CIN2 or CIN3 in Women Infected with the
      Human Immunodeficiency Virus.

PMID- 25950316
TI  - Predictors of CIN in Women with ASCUS and LGSIL Cytology.

PMID- 25950318
TI  - HPV DNA Testing by Hybrid Capture Does Not Appear to be Useful in the Triage of
      Cytology Read as ASCUS-Favor Dysplasia, or as LGSIL.

PMID- 25950319
TI  - Bipolar loop electrosurgical excision procedure for cervical intraepithelial
      neoplasia.

PMID- 25950320
TI  - Predicting risk factors for suboptimal excision in women undergoing cone biopsy.

PMID- 25950321
TI  - Colposcopic and cytological follow-up of women treated by loop excision.

PMID- 25950322
TI  - Human papillomavirus testing versus multivariate tree analysis of demographic
      data in the triage of patients with mild cytological dysplasia.

PMID- 25950323
TI  - A Comparison of Flat and Shallow Conical Cervical Cryotherapy Tips: Elimination
      of CIN and Posttreatment Location of the Squamocolumnar Junction.

PMID- 25950324
TI  - Angiogenesis in histologically benign squamous mucosa is a sensitive marker for
      nearby cervical intraepithelial neoplasia.

PMID- 25950325
TI  - The prevalence of cervical pathology in a high-risk population screened with
      cytology, cervicography, and hybrid capture.

PMID- 25950326
TI  - Is there a role for cervicography in the detection of cervical dysplasia of the
      uterine cervix?

PMID- 25950327
TI  - HPV Testing by Hybrid Capture Assay Is a Valuable Second-Level Screening
      Procedure in Triage of Women with ASCUS Favor Reactive and ASCUS Favor Dysplasia
      Pap Smears.

PMID- 25950328
TI  - A comparison of colposcopy using optical and video colposcopes.

PMID- 25950330
TI  - Utility-and Cost-Effectiveness of PAPNET Secondary Screening Technology for
      Cervical Cytology.

PMID- 25950329
TI  - Identification of squamous intraepithelial lesions: fluorescence of cervical
      tissue during colposcopy.

PMID- 25950331
TI  - Atypical squamous cells of undetermined significance: management patterns at an
      academic medical center.

PMID- 25950332
TI  - Prevalence of high-grade neoplasia in patients with mildly abnormal cytology: is
      there a clinically significant difference between atypia and a low-grade squamous
      intraepithelial lesion?

PMID- 25950333
TI  - Psychosocial distress and colposcopy.

PMID- 25950334
TI  - Regression of cervical intraepithelial neoplasia grade 1 to normal in the primary
      care setting.

PMID- 25950335
TI  - Cervicography in the assessment of women with minor cytologic abnormalities.

PMID- 25950336
TI  - Abnormal papanicolaou smear potential in college health: 1989-1996.

PMID- 25950337
TI  - A comparison of an endocervical curettage with syringe aspirator to the standard
      kevorkian curette technique.

PMID- 25950338
TI  - Evaluation of the cone biopsy excisor as compared with the large loop for
      electrosurgical excision of cervical lesions.

PMID- 25950339
TI  - A longitudinal study of papanicolaou smear plus speculoscopy: value of delaying
      colposcopy in women with positive speculoscopy only.

PMID- 25950340
TI  - Comparison of Physician and Nurse Practitioner Colposcopic Quality of Care for
      Patients Referred with ASCUS Papanicolaou Smears in a Health Maintenance
      Organization.

PMID- 25950342
TI  - Pseudo-Paget's Disease of the Vulva: A Case Report.

PMID- 25950341
TI  - Case report of a endometrial lipoma and review of the literature.

PMID- 25950343
TI  - Arteritis limited to the uterine cervix.

PMID- 25950344
TI  - Sustained improvement in vulvodynia symptoms with interferon injections.

PMID- 25950345
TI  - Colposcopic prediction: role of cytology and images.

PMID- 25950346
TI  - Adherence to Colposcopic Evaluation Among HIV-Infected Women.

PMID- 25950347
TI  - The accuracy of colposcopic impression among women undergoing directed biopsy.

PMID- 25950348
TI  - Pregnancies in women treated by loop excision.

PMID- 25950349
TI  - Cervical conization: are negative margins predictive of residual dysplasia in
      hysterectomy specimens?

PMID- 25950350
TI  - A Comparison of Two Methods Used in Managing Severe Cervical Dysplasia: LLETZ and
      Cone Biopsy.

PMID- 25950351
TI  - Colposcopic Findings in the Evaluation of ASCUS Papanicolaou Smears.

PMID- 25950352
TI  - Cervical cytology and other screening methods among women admitted to the medical
      intensive care unit.

PMID- 25950353
TI  - Home study course: winter 1999.

PMID- 25950354
TI  - Management of patient with iud who is to undergo a cone biopsy.

PMID- 25950355
TI  - A case of severe hidradenitis suppurativa contributing to a death and a review of
      the literature.
AB  - OBJECTIVE: Our aim was to report a fatal complication of hidradenitis suppurativa
      and a review of the literature. MATERIALS AND METHODS: A case of severe
      hidradenitis suppurativa obscuring the diagnosis and precluding the treatment of
      a ruptured sigmoid diverticulum is presented. RESULTS: We describe a 48-year-old
      woman who had a long history of untreated hidradenitis suppurativa with extensive
      vulvar involvement and poor nutritional status. The advanced state of her disease
      on initial presentation led directly to her death. CONCLUSION: Although it is a
      treatable disease, hidradenitis suppurativa can lead to systemic sequelae severe
      enough to contribute directly to death.

PMID- 25950356
TI  - Localized chrysiasis, aluminum salt deposition and dystrophic calcification a
      decade after gold injections.
AB  - Localized chrysiasis is rare and can occur in two settings: after localized or
      traumatic implantation of elemental gold or gold salts or after localized laser
      or light therapy in someone who has been previously exposed to systemic gold
      therapy. We report a unique case of localized chrysiasis with associated aluminum
      salt deposition and sclerosing lipogranulomas because of previous injections of
      aurothioglucose (Solganal(r)). The unique histopathologic findings seen in this
      case have not been previously reported. 

PMID- 25950357
TI  - Death attitudes and positive coping in Spanish nursing undergraduates: a cross
      sectional and correlational study.
AB  - AIMS AND OBJECTIVES: To analyse the relationship between death attitudes,
      emotional intelligence, resilience and self-esteem in a sample of nursing
      undergraduates. BACKGROUND: The death attitudes held by nursing students may
      influence the care they offer to end-of-life patients and their families.
      Emotional intelligence, resilience and self-esteem are important social and
      emotional competencies for coping positively with death and dying. DESIGN: Cross
      sectional and correlational study. METHODS: Participants were 760 nursing
      undergraduates from four nursing schools in Spain. Data were collected in 2013
      2014. The students responded anonymously to a self-report questionnaire that
      gathered socio-demographic data and which assessed the following aspects: fear of
      death (Collett-Lester Fear of Death Scale), death anxiety (Death Anxiety
      Inventory-Revised), perceived emotional intelligence (Trait Meta-Mood Scale, with
      its three dimensions: attention, clarity and repair), resilience (Brief Resilient
      Coping Scale) and self-esteem (Rosenberg Self-Esteem Scale). In addition to
      descriptive statistics, analyses of variance, mean differences, correlations and
      regression analyses were computed. RESULTS: Linear regression analysis indicated
      that attention to feelings, resilience and self-esteem are the significant
      predictors of death anxiety. CONCLUSIONS: The results show that death anxiety and
      fear of death are modulated by social and emotional competencies associated with
      positive coping. RELEVANCE TO CLINICAL PRACTICE: The training offered to future
      nurses should include not only scientific knowledge and technical skills but also
      strategies for developing social and emotional competencies. In this way, they
      will be better equipped to cope positively and constructively with the suffering
      and death they encounter at work, thus helping them to offer compassionate
      patient-centred care and minimising the distress they experience in the process.

PMID- 25950358
TI  - Violence on campus: we all have a role to play.

PMID- 25950360
TI  - Diversity of nursing student views about simulation design: a q-methodological
      study.
AB  - BACKGROUND: Education of future nurses benefits from well-designed simulation
      activities. Skillful teaching with simulation requires educators to be constantly
      aware of how students experience learning and perceive educators' actions.
      Because revision of simulation activities considers feedback elicited from
      students, it is crucial to understand the perspective from which students base
      their response. METHOD: In a Q-methodological approach, 45 nursing students rank
      ordered 60 opinion statements about simulation design into a distribution grid.
      RESULTS: Factor analysis revealed that nursing students hold five distinct and
      uniquely personal perspectives-Let Me Show You, Stand By Me, The Agony of Defeat,
      Let Me Think It Through, and I'm Engaging and So Should You. CONCLUSION: Results
      suggest that nurse educators need to reaffirm that students clearly understand
      the purpose of each simulation activity. Nurse educators should incorporate
      presimulation assignments to optimize learning and help allay anxiety. The five
      perspectives discovered in this study can serve as a tool to discern individual
      students' learning needs.

PMID- 25950359
TI  - The faculty voice: teaching in accelerated second baccalaureate degree nursing
      programs.
AB  - BACKGROUND: Although accelerated second baccalaureate degree in nursing (ASBSN)
      programs are growing, little is known about how faculty help ASBSN students to
      learn. METHOD: In this descriptive qualitative study, faculty in 25 ASBSN
      programs in 11 midwestern states were asked to describe factors about their
      teaching. These focused on a comparison with traditional education and an in
      depth examination of teaching strategies. RESULTS: Faculty (N = 129) responded to
      six open-ended questions on the online survey; a thematic analysis resulted in 24
      themes. Themes included Appreciate the Adult Learner With Previous Experiences;
      Connect Students With Structured Professional Activities; Role Model Professional
      Learning; and I Like It, I Love It, I Enjoy the Challenge of It. CONCLUSION:
      Because findings are from the faculty perspective, they enhance understanding of
      this teaching experience. Implications for faculty development and further
      research are included.

PMID- 25950361
TI  - Underrepresented students' perspectives on institutional climate during the
      application and admission process to nursing school.
AB  - BACKGROUND: A growing body of literature has focused on issues related to
      recruitment and retention to enhance diversity in nursing. This study was
      designed to identify barriers and supports encountered by underrepresented
      students when applying to nursing school. METHOD: Twenty-two underrepresented
      baccalaureate nursing students participated in two focus groups. Applied thematic
      analysis was used to organize the data and identify major themes. RESULTS:
      Students expressed the importance of having (a) navigators in the offices of
      admissions and student affairs to provide encouragement, support, and information
      during the application process; (b) tailored programming for underrepresented
      students; (c) financial aid guidance; (d) timely feedback about admissions
      decisions; (e) a clear and easily navigated Web site; and (f) negotiation and
      acculturation to know the right things to do and say during the application and
      admissions process. CONCLUSION: Findings provide direction for developing
      programming and collaborations to enhance the institutional climate for
      underrepresented nursing applicants. [J Nurs Educ. 2015;54(5):261-269.].

PMID- 25950362
TI  - First-year nursing students-developing relational caring practice through
      inquiry.
AB  - BACKGROUND: In the current chaotic health care milieu, it is a challenge to
      create learning environments that support students to become respectful and
      community-engaged practitioners who are able to care for self and others.
      Aesthetic and transformative learning approaches foster students to develop
      caring attributes. METHOD: Using relational inquiry and the general principles of
      transformative learning theory, an aesthetic curriculum project for first-year
      nursing students exploring the interrelatedness of self, other, and caring was
      developed and evaluated by nursing faculty. RESULTS: Students' in-the-moment
      experiences of transitioning into nursing school were enlisted to (a) open the
      space for deeper learning, (b) support the development of relational caring
      practice, and (c) foster personal and professional transformations. CONCLUSION:
      Aesthetic learning opportunities create experiential moments, where novice
      students can begin to explore the interconnectedness of self, other, and caring
      as it relates to their being and becoming a nurse.

PMID- 25950363
TI  - Does Prior RN Clinical Experience Predict Academic Success in Graduate Nurse
      Practitioner Programs?
AB  - BACKGROUND: There is limited evidence on whether prior RN clinical experience is
      predictive of academic success in graduate nurse practitioner (NP) programs. The
      purpose of this study was to explore whether the frequently held assumption that
      more prior clinical experience is associated with better academic success in The
      George Washington University online NP programs. METHOD: Applications (n = 106)
      for clinical NP students entering from 2008-2010 were examined along with data on
      academic performance. RESULTS: No relationship was found between years of prior
      RN clinical experience and three educational outcome variables (cumulative grade
      point average [GPA], clinical course GPA, and having failed any courses or been
      put on probation). However, students with the most prior RN clinical experience
      were less likely to graduate in 4 years, compared with those with the least
      experience. CONCLUSION: These findings serve as a building block of empirical
      evidence for admissions committees as they consider entry requirements for NP
      programs.

PMID- 25950364
TI  - Introduction of unresponsive patient simulation scenarios into an undergraduate
      nursing health assessment course.
AB  - BACKGROUND: Despite certification in basic life support, nursing students may not
      be proficient in performing critical assessments and interventions for
      unresponsive patients. Thus, a new simulation module comprising four unresponsive
      patient scenarios was introduced into a second-year nursing health assessment
      course. METHOD: This cross-sectional study describes nursing student experience,
      knowledge, confidence, and performance of assessments and interventions for the
      unresponsive patient across 3 years of an undergraduate nursing program. RESULTS:
      Overall knowledge, confidence, and performance scores were similar between second
      , third-, and fourth-year students (N = 239); however, performance times for many
      critical assessments and interventions were poor. Second-year nursing students'
      knowledge increased significantly following the new simulation module (p =
      0.002). CONCLUSION: Findings suggest a need for more repetition of basic
      unresponsive patient scenarios to provide mastery. It is anticipated that
      addition of unresponsive patient scenarios into the second year will enhance
      performance by the final year of the program.

PMID- 25950365
TI  - Evaluating the effectiveness of real-time feedback on the bedside hand hygiene
      behaviors of nursing students.
AB  - BACKGROUND: Traditional hand hygiene teaching methods lack long-term
      effectiveness. METHOD: A longitudinal, within-subject design explored the
      influence of real-time hand microbe feedback and a critical-thinking decision
      exercise on nursing student hand hygiene behaviors. In three community hospitals,
      the students' (n = 68) hand swabs were tested for normal flora, methicillin
      resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus at
      three time points. Students completed the Partnering to Heal (PTH) online
      exercise on hospital-acquired infection prevention decisions. RESULTS: Normal
      flora colony counts decreased across the semester and MRSA-positive cultures
      increased in frequency and colony counts. MRSA-positive cultures were not
      associated with caring for patients in isolation precautions. Significantly
      higher colony counts were noted in the students who completed the PTH than those
      who did not complete the PTH. CONCLUSION: This study explores innovative pedagogy
      bringing the nonvisible microbial risk to the consciousness of nursing students
      in an attempt to change hand hygiene behaviors.

PMID- 25950366
TI  - Short message service use in clinical care through a simulation activity.
AB  - BACKGROUND: Research has shown that the integration of informatics competencies
      into nursing education especially for Doctor of Nursing Practice (DNP) students,
      has been inadequate. This article reports on a Short Message Service (SMS)
      simulation activity for incorporating informatics knowledge and skills into the
      DNP curriculum. METHOD: DNP students participated in a 3-week simulated
      ecological momentary assessment using SMS technology. Students rated their
      experience through a survey and wrote a 1 page narrative describing their
      experience. Data were analyzed using descriptive statistics and open-ended
      coding. RESULTS: This simulation activity provided information for the future
      delivery of care using SMS. The cost-saving potential of follow-up messaging
      reimbursement for providers who use SMS may be a worthwhile investment of health
      care payers. CONCLUSIONS: This activity demonstrated the usefulness of SMS
      technology for helping patients manage their chronic health conditions. Use of
      SMS would be a reinforcing factor for providers in clinical care if it becomes
      reimbursable.

PMID- 25950367
TI  - Establishment of a short-term global health nursing education experience: impact
      on students' ways of knowing.
AB  - BACKGROUND: The Essentials of Baccalaureate Education for Professional Nursing
      recognizes that with the increased globalization of health care, professional
      nurses have to be prepared to practice in multicultural environments and must
      possess the skills needed to provide culturally competent care. METHOD: Thirty
      five baccalaureate nursing students participated in a short-term course abroad to
      Jamaica over a period of 3 years. The impact of such an experience on ways of
      knowing was assessed in 20 participants, using a visual analog scale. RESULTS:
      Students believed that the short-term course abroad experience had a positive
      impact on their personal knowing and that they developed an understanding of a
      health care system different from their own, while reflecting on issues of social
      justice. CONCLUSION: Results provide evidence of the positive impact on short
      term course abroad trips on students' ways of knowing. Critical to establishment
      of these experiences is evaluation of their merit through documentation of
      student learning outcomes.

PMID- 25950368
TI  - Creating your ideal primary care practice: innovative interprofessional learning
      activity.

PMID- 25950369
TI  - Cancer Information Seeking Behaviors of Korean American Women: A Mixed-Methods
      Study Using Surveys and Focus Group Interviews.
AB  - Despite the high risk of cancer to the population, Korean Americans are known to
      have lower knowledge about cancer related information and a lower level of
      adherence to cancer prevention guidelines. This indicates the necessity of cancer
      interventions targeting the Korean American population. To reach this population
      effectively, it is imperative to understand Korean Americans' cancer information
      seeking behaviors. This study (a) identified cancer information sources that are
      trusted and used by Korean American women and (b) examined how general media
      exposure and trust in cancer information sources are related to the use of these
      sources. It also (c) explored perceived usefulness and limitations of cancer
      information sources. A mixed methods study using seven focus group interviews
      with 34 Korean American women and surveys with 152 Korean American women was
      conducted in the Washington, DC, metropolitan area from 2011 to 2012. The results
      indicate that Korean American women viewed health care professionals as the most
      trusted cancer information source but used the Internet and Korean ethnic media
      more often for cancer information seeking because of language, cultural, and
      economic barriers. Korean American women were most likely to obtain cancer
      information from media they used frequently for general purposes. Correlations
      between usage frequency and trust in doctor/health providers and the Internet as
      cancer information sources were negligible. When seeking cancer information,
      important factors for Korean American women were accessibility, affordability,
      and language proficiency, cultural sensitivity, meeting immediate needs,
      understandability, convenience, and reliability of cancer information sources.
      Findings from this study support developing interventions using Korean language
      media, including print, television and the Internet for health promotion and
      cancer prevention targeting Korean American women. 

PMID- 25950370
TI  - Vascular plant abundance and diversity in an alpine heath under observed and
      simulated global change.
AB  - Global change is predicted to cause shifts in species distributions and
      biodiversity in arctic tundra. We applied factorial warming and nutrient
      manipulation to a nutrient and species poor alpine/arctic heath community for
      seven years. Vascular plant abundance in control plots increased by 31%. There
      were also notable changes in cover in the nutrient and combined nutrient and
      warming treatments, with deciduous and evergreen shrubs declining, grasses
      overgrowing these plots. Sedge abundance initially increased significantly with
      nutrient amendment and then declined, going below initial values in the combined
      nutrient and warming treatment. Nutrient addition resulted in a change in
      dominance hierarchy from deciduous shrubs to grasses. We found significant
      declines in vascular plant diversity and evenness in the warming treatment and a
      decline in diversity in the combined warming and nutrient addition treatment,
      while nutrient addition caused a decline in species richness. The results give
      some experimental support that species poor plant communities with low diversity
      may be more vulnerable to loss of species diversity than communities with higher
      initial diversity. The projected increase in nutrient deposition and warming may
      therefore have negative impacts on ecosystem processes, functioning and services
      due to loss of species diversity in an already impoverished environment. 

PMID- 25950371
TI  - FHIT loss confers cisplatin resistance in lung cancer via the AKT/NF-kappaB/Slug
      mediated PUMA reduction.

PMID- 25950372
TI  - Extracorporeal treatment for valproic acid poisoning: systematic review and
      recommendations from the EXTRIP workgroup.
AB  - BACKGROUND: The EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup
      presents its systematic review and clinical recommendations on the use of
      extracorporeal treatment (ECTR) in valproic acid (VPA) poisoning. METHODS: The
      lead authors reviewed all of the articles from a systematic literature search,
      extracted the data, summarized the key findings, and proposed structured voting
      statements following a predetermined format. A two-round modified Delphi method
      was chosen to reach a consensus on voting statements and the RAND/UCLA
      Appropriateness Method was used to quantify disagreement. Anonymous votes were
      compiled, returned, and discussed in person. A second vote was conducted to
      determine the final workgroup recommendations. RESULTS: The latest literature
      search conducted in November 2014 retrieved a total of 79 articles for final
      qualitative analysis, including one observational study, one uncontrolled cohort
      study with aggregate analysis, 70 case reports and case series, and 7
      pharmacokinetic studies, yielding a very low quality of evidence for all
      recommendations. Clinical data were reported for 82 overdose patients while
      pharmaco/toxicokinetic grading was performed in 55 patients. The workgroup
      concluded that VPA is moderately dialyzable (level of evidence = B) and made the
      following recommendations: ECTR is recommended in severe VPA poisoning (1D);
      recommendations for ECTR include a VPA concentration > 1300 mg/L (9000
      MUmol/L)(1D), the presence of cerebral edema (1D) or shock (1D); suggestions for
      ECTR include a VPA concentration > 900 mg/L (6250 MUmol/L)(2D), coma or
      respiratory depression requiring mechanical ventilation (2D), acute
      hyperammonemia (2D), or pH <= 7.10 (2D). Cessation of ECTR is indicated when
      clinical improvement is apparent (1D) or the serum VPA concentration is between
      50 and 100 mg/L (350-700 MUmol/L)(2D). Intermittent hemodialysis is the preferred
      ECTR in VPA poisoning (1D). If hemodialysis is not available, then intermittent
      hemoperfusion (1D) or continuous renal replacement therapy (2D) is an acceptable
      alternative. CONCLUSIONS: VPA is moderately dialyzable in the setting of
      overdose. ECTR is indicated for VPA poisoning if at least one of the above
      criteria is present. Intermittent hemodialysis is the preferred ECTR modality in
      VPA poisoning.

PMID- 25950374
TI  - Seeing and Being Green? The Effect of Money Priming on Willingness to Perform
      Sustainable Actions, Social Connectedness, and Prosociality.
AB  - This investigation attempted to conceptually replicate/extend research that
      suggests that reminders of money can inhibit prosociality, promote self
      sufficiency, and influence political beliefs. Based on these results, we
      hypothesized that money primes would decrease willingness to engage in
      sustainable actions. We also predicted that people would distribute points less
      prosocially and feel less socially connected when money was primed. Individuals
      were recruited from an undergraduate participant pool and MTurk. Meta-analytic
      results across the two samples revealed that money priming did not have a
      significant impact on willingness to act sustainably, but it did cause
      participants to distribute points less prosocially and report lower social
      connectedness than individuals in the control condition. While effects were
      smaller than those reported in Vohs, Mead, and Goode (2006), this study still
      offers support for the detrimental impact of reminders of money on interpersonal
      relations. 

PMID- 25950375
TI  - Different strategies, but indifferent strategy adaptation during action
      cascading.
AB  - Every day, we need to apply different action control strategies to successfully
      interact with ever-changing environments. In situations requiring several
      responses, we often have to cascade different actions. The strategies used to
      accomplish this have been subject to extensive research in cognitive psychology
      and neuroscience but it has remained rather unclear if and to what degree such
      strategies are adapted while performing a task. Furthermore, we do not know if
      such adaptations are subject to differential effects depending on an individual's
      preferred initial strategy to cope with multiple-demand situations. Using
      Bayesian analyses, we were able to show that even though the applied strategy is
      subject to slight modulations over the course of an action cascading task, this
      shift is equally strong for subjects who differ their general action cascading
      strategy. The action cascading strategy subjects apply to cope with multiple
      demand situations is adapted independent of the preferred, inter-individually
      varying strategy that is initially used. Future research needs to test if the
      task goal activation strategy applied during action cascading reflects a
      'cognitive trait' and is stable across different situations. 

PMID- 25950376
TI  - Pathological and problem gambling in substance use treatment: Results from the
      National Epidemiologic Survey on Alcohol and Related Conditions (NESARC).
AB  - BACKGROUND AND OBJECTIVES: Pathological and problem gambling may be common yet
      frequently undetected conditions in substance use treatment. This paper reports
      findings on the prevalence of gambling comorbidities in these clinical contexts
      that are generalizable across regions and settings. It indicates the implications
      of such conditions for treatment of substance use problems. METHODS: A U.S.
      representative sample of n = 402 patients reporting past-year treatment for
      substance use problems was derived from wave 1 and 2 of the National
      Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Weighted
      prevalence estimates were produced and regression analyses used to examine
      correlates of gambling symptoms. RESULTS: Rates of lifetime pathological gambling
      (5+ DSM-IV symptoms) and problem gambling (3+ DSM-IV symptoms) were 4.3% (s.e. =
      1.3%) and 7.2% (s.e. = 1.6%), respectively. Lifetime gambling symptoms were
      associated with Axis II disorders, but no Axis I diagnoses. There was limited
      evidence of associations with substance usage, mental or physical health and
      medical utilization. There were associations with financial crises and
      relationship breakdown, during and after treatment. CONCLUSIONS AND SCIENTIFIC
      SIGNIFICANCE: Gambling problems are elevated in substance use treatment but may
      be less common than previously thought; when considered nationally and across
      clinical settings. They may have modest associations with clinical
      characteristics given high levels of psychiatric severity that characterise
      treatment seeking samples overall. Notwithstanding, the results suggest that
      gambling comorbidities should be standard considerations in substance use
      treatment. They may signal complex conditions characterised by pervasive
      underlying psychopathology, and psychosocial difficulties that accumulate over
      time.

PMID- 25950377
TI  - In Vitro Study of Surface Modified Poly(ethylene glycol)-Impregnated Sintered
      Bovine Bone Scaffolds on Human Fibroblast Cells.
AB  - Scaffold design from xenogeneic bone has the potential for tissue engineering
      (TE). However, major difficulties impede this potential, such as the wide range
      of properties in natural bone. In this study, sintered cortical bones from
      different parts of a bovine-femur impregnated with biodegradable poly(ethylene
      glycol) (PEG) binder by liquid phase adsorption were investigated. Flexural
      mechanical properties of the PEG-treated scaffolds showed that the scaffold is
      stiffer and stronger at a sintering condition of 1000 degrees C compared with 900
      degrees C. In vitro cytotoxicity of the scaffolds evaluated by Alamar Blue assay
      and microscopic tests on human fibroblast cells is better at 1000 degrees C
      compared with that at 900 degrees C. Furthermore, in vitro biocompatibility and
      flexural property of scaffolds derived from different parts of a femur depend on
      morphology and heat-treatment condition. Therefore, the fabricated scaffolds from
      the distal and proximal parts at 1000 degrees C are potential candidates for hard
      and soft TE applications, respectively. 

PMID- 25950378
TI  - Effect of the rs1051730-rs16969968 variant and smoking cessation treatment: a
      meta-analysis.
AB  - OBJECTIVE: To assess if the allelic variations of rs16969968/rs1051730 in the
      CHRNA5-CHRNA3-CHRNB4 gene cluster are associated with smoking cessation after
      nicotine replacement therapy (NRT). METHODS: We searched for NRT studies
      published from 2000-2013 that reported counts for allelic variation of
      rs16969968/rs1051730 and measured abstinence rates at the end of NRT treatment.
      We identified four studies which met the criteria, giving us a test sample of
      2036 participants. RESULTS: There was no effect of rs16969968/rs1051730 in
      influencing the success rate at the end of NRT (n = 6, effect size [ES]: 0.969,
      95% CI: 0.77 to 1.23, z = 0.27, p = 0.791). CONCLUSION: There is no robust
      evidence that allelic variations of rs16969968 or rs1051730 are associated with
      smoking cessation after NRT. Original submitted 26 November 2014; Revision
      submitted 9 March 2015.

PMID- 25950379
TI  - Solute-solute correlations responsible for the prepeak in structure factors of
      undercooled Al-rich liquids: a molecular dynamics study.
AB  - We have performed molecular dynamics simulations on a typical Al-based alloy
      Al90Sm10. The short-range and medium-range correlations of the system are
      reliably produced by ab initio calculations, whereas the long-range correlations
      are obtained with the assistance of a semi-empirical potential well-fitted to ab
      initio data. Our calculations show that a prepeak in the structure factor of this
      system emerges well above the melting temperature, and the intensity of the
      prepeak increases with increasing undercooling of the liquid. These results are
      in agreement with x-ray diffraction experiments. The interplay between the short
      range order of the system originating from the large affinity between Al and Sm
      atoms, and the intrinsic repulsion between Sm atoms gives rise to a stronger
      correlation in the second peak than the first peak in the Sm-Sm partial pair
      correlation function (PPCF), which in turn produces the prepeak in the structure
      factor. 

PMID- 25950380
TI  - Chemical and material communication between the optic nerves in rats.
AB  - BACKGROUND: To examine interactions between optic nerves. METHODS: A total of 24
      Sprague-Dawley rats received unilateral intravitreal injections. The rats were
      equally divided into four groups: group A was administered an adeno-associated
      virus (AAV) carrying an exogenous gene (ND4; rAAV-ND4); group B, AAV carrying a
      green fluorescent protein (GFP; rAAV-GFP); group C, fluorogold (FG) nerve tracer
      dye; and group D, phosphate-buffered saline (PBS) as a control. Two weeks later,
      GFP expression was evaluated in both retinas and optic nerves of group B rats
      after frozen sectioning. The presence of FG was also evaluated in group C optic
      nerves by fluorescent microscopy after frozen sectioning. Four weeks after
      injection, ND4 expression was evaluated in both eyes of groups A and D using
      western blotting and immunofluorescence. RESULTS: FG was observed in the optic
      chiasm posterior segment along the optic nerve of injected eyes. Some FG reached
      the anterior optic nerve of the non-injected eye. GFP fluorescence was observed
      only in the retina of the injected eye but not in the contralateral retina or
      either optic nerve. ND4 expression was significantly different between injected
      and non-injected eyes but not between the non-injected eyes in groups A and D.
      CONCLUSION: Unilaterally injected material can reach the contralateral optic
      nerve through axoplasmic transport. It is possible that this the only mechanism
      by which the optic nerves directly communicate.

PMID- 25950381
TI  - The origin of endodontic Enterococcus faecalis explored by comparison of
      virulence factor patterns and antibiotic resistance to that of isolates from
      stool samples, blood cultures and food.
AB  - AIM: To elucidate the origin of Enterococcus faecalis isolated from secondary
      root canal infections and the possibility for a foodborne transmission by
      comparing them to strains recovered from food, blood and stool regarding putative
      virulence factors and antibiotic susceptibility profiles, where strains from
      common origin were hypothesized to harbour similar characteristics. METHODOLOGY:
      A total of 108 E. faecalis strains recovered in the county of Stockholm, Sweden,
      were screened using PCR for putative virulence factors esp, cylA, gelE/gelatinase
      negative phenotype (ef1841/fsrC), efaA, ace and asa1. The minimum inhibitory
      concentration (MIC) for ampicillin, piperacillin-tazobactam, imipenem,
      gentamicin, vancomycin, ciprofloxacin and linezolid was determined using the agar
      dilution method. RESULTS: Next to strains from blood, the food isolates presented
      the highest average number of virulence determinants and were frequently enriched
      with asa1 coding for aggregation substance. None of the endodontic strains
      carried cylA, and the gelatinase-negative phenotype caused by a deletion
      dominated the group. Altogether, the most prevalent genes were gelE, efaA and
      ace, and a combination of them was equally present in approximately 80% of the
      strains from food, stool and root canals in comparison with 43.3% of the blood
      isolates. High-level resistance to ciprofloxacin and gentamicin was observed in
      30% of the blood isolates, whereas the isolates from other origins, with single
      exceptions, were susceptible to all tested antibiotics. CONCLUSIONS: Evidence for
      a foodborne transmission, explaining the high reported prevalence of E. faecalis
      in root filled teeth, could not be determined based on the similarities in
      virulence factor patterns and antibiotic susceptibility. The only linkage between
      isolates from food and root canals consisted of a shared common combination of
      the genes gelE, efaA and ace. The high occurrence of putative virulence traits in
      food isolates questions the safety of E. faecalis in food products.

PMID- 25950382
TI  - Identifying educational priorities for occupational therapy students to prepare
      for mental health practice in Australia and New Zealand: Opinions of practising
      occupational therapists.
AB  - BACKGROUND: The effective preparation of occupational therapy students for mental
      health practice is critical to facilitate positive consumer outcomes, underpin
      optimal practice and support new graduates' professional identity. This project
      was established to determine a set of 'educational priorities' for occupational
      therapy students to prepare them for current (and future) entry-level practice in
      mental health, from the perspective of mental health occupational therapists in
      Australia and New Zealand. METHODS: The study included two phases. In Phase One,
      participants identified what they considered to be important educational
      priorities for occupational therapy students to prepare them for practice in
      mental health. For Phase Two, an 'expert panel' was assembled to review and rank
      these using a Policy Delphi approach. RESULTS: Eighty-five participants provided
      educational priorities in Phase One. These were grouped into a total of 149
      educational themes. In Phase Two, the expert panel (consisting of 37 occupational
      therapists from diverse locations and practice settings) prioritised these themes
      across three Delphi rounds. A final priority list was generated dividing
      educational themes into three prioritised categories: 29 'Essential', 25
      'Important' and 44 'Optional' priorities. Highest-ranked priorities were:
      clinical reasoning, client-centred practice, therapeutic use of self, functional
      implications of mental illness, therapeutic use of occupation and mental health
      fieldwork experience. CONCLUSION: The priority list developed as part of this
      project provides additional information to support the review of occupational
      therapy curricula across Australia and New Zealand to ensure that new graduates
      are optimally prepared for mental health practice.

PMID- 25950383
TI  - Proteome characterization of melanoma exosomes reveals a specific signature for
      metastatic cell lines.
AB  - Exosomes are important mediators in cell-to-cell communication and, recently,
      their role in melanoma progression has been brought to light. Here, we
      characterized exosomes secreted by seven melanoma cell lines with varying degrees
      of aggressivity. Extensive proteomic analysis of their exosomes confirmed the
      presence of characteristic exosomal markers as well as melanoma-specific antigens
      and oncogenic proteins. Importantly, the protein composition differed among
      exosomes from different lines. Exosomes from aggressive cells contained specific
      proteins involved in cell motility, angiogenesis, and immune response, while
      these proteins were less abundant or absent in exosomes from less aggressive
      cells. Interestingly, when exposed to exosomes from metastatic lines, less
      aggressive cells increased their migratory capacities, likely due to transfer of
      pro-migratory exosomal proteins to recipient cells. Hence, this study shows that
      the specific protein composition of melanoma exosomes depends on the cells'
      aggressivity and suggests that exosomes influence the behavior of other tumor
      cells and their microenvironment. 

PMID- 25950384
TI  - Different prognostic models for different patient populations: validation of a
      new prognostic model for patients with oropharyngeal cancer in Western Europe.
AB  - OBJECTIVE: The presence of human papillomavirus (HPV) infection in oropharyngeal
      squamous cell carcinoma (OPSCC) is a major determinant in prognostic risk
      modelling. Recently, a prognostic model was proposed in which HPV status,
      comorbidity and nodal stage were the most important prognostic factors to
      determine high-, intermediate- and low-risk survival groups. Here, we report on
      the validation of this model using an independent single-institutional cohort.
      METHODS: A total number of 235 patients curatively treated for OPSCC in the
      period 2000-2011 at the MUMC (Maastricht University Medical Center, The
      Netherlands) were included. The presence of an oncogenic HPV infection was
      determined by p16 immunostaining, followed by a high-risk HPV DNA PCR on the p16
      positive cases. The model variables included were HPV status, comorbidity and
      nodal stage. As a measure of model performance, the Harrell's Concordance index
      (Harrell's C-index) was used. RESULTS: The 5-year overall survival (OS) estimates
      were 84.6%, 54.5% and 28.7% in the low-, intermediate- and high-risk group,
      respectively. The difference between the survival curves was highly significant
      (P<0.001). The Harrell's C-index was 0.69 (95% confidence interval (CI): 0.63
      0.75). CONCLUSION: In this study a previously developed prognostic risk model was
      validated. This model will help to personalise treatment in OPSCC patients. This
      model is publicly available at www.predictcancer.org.

PMID- 25950385
TI  - Smoking is associated with pessimistic and avoidant beliefs about cancer: results
      from the International Cancer Benchmarking Partnership.
AB  - BACKGROUND: Smoking cessation is the key cancer prevention behaviour for smokers;
      nonetheless, smokers can still benefit from earlier diagnosis of cancer. However,
      fewer smokers participate in screening despite their increased risk, which may
      reflect different beliefs about cancer. METHODS: A UK population-representative
      sample of ?50 year-olds (n=6965) was surveyed using the Awareness and Beliefs
      about Cancer measure. These analyses examine six items on cancer beliefs (e.g.,
      'cancer can often be cured'), and four on help-seeking barriers (e.g., 'I would
      be too embarrassed'). RESULTS: Smokers were more likely to hold pessimistic
      cancer beliefs than never-smokers or former-smokers on four of six items. For
      example, 34% agreed 'a cancer diagnosis is a death sentence', compared with 24%
      of non/former-smokers (P<0.001). More smokers (18%) than non/former-smokers (11%)
      would not want to know if they had cancer (P<0.01). The only barrier to
      symptomatic help-seeking differing by smoking status was 'worry about what the
      doctor might find' (36% vs 28%, P<0.01). Associations were independent of
      demographics, self-rated health and cancer experience. CONCLUSIONS: Smokers held
      more pessimistic and avoidant beliefs about cancer, which could deter early
      detection behaviour. A better understanding of these beliefs is needed to
      increase engagement in early diagnosis by this high-risk group.

PMID- 25950387
TI  - MT95-4, a fully humanized antibody raised against aminopeptidase N, reduces tumor
      progression in a mouse model.
AB  - Aminopeptidase N (APN/CD13) is involved in tumor cell invasion and tumor
      angiogenesis and is considered a promising therapeutic target in the treatment of
      cancer. To develop a novel monoclonal antibody-based cancer therapy targeting
      APN/CD13, we established a fully humanized anti-APN/CD13 monoclonal antibody,
      MT95-4. In vitro, MT95-4 inhibited APN/CD13 enzymatic activity on the tumor cell
      surface and blocked tumor cell invasion. B16 mouse melanoma cells stably
      expressing human APN/CD13 were also established and were inoculated s.c. or
      injected i.v. into nude mice. We found that expression of human APN/CD13 in
      murine melanoma cells increased the size of subcutaneous tumors, extent of lung
      metastasis and degree of angiogenesis in the subcutaneous tumors; these tumor
      promoting and angiogenesis-promoting characteristics were reduced by the i.p.
      administration of MT95-4. To further verify the specificity of MT95-4 for
      neutralization of APN/CD13 activity, MT95-4 was administered into NOD/SCID mice
      inoculated s.c. with H1299 or PC14 cells, which exhibit high expression of
      APN/CD13, or with A549 cells, which exhibit weak expression of APN/CD13. MT95-4
      reduced tumor growth and angiogenesis in mice bearing H1299-derived and PC14
      derived tumors, but not in mice bearing A549-derived tumors. These results
      suggested that the antitumor and anti-angiogenic effects of MT95-4 were dependent
      on APN/CD13 expression in tumor cells. Given that MT95-4 is the first fully
      humanized monoclonal antibody against APN/CD13, MT95-4 should be recognized as a
      promising candidate for monoclonal antibody therapy against tumors expressing
      APN/CD13. 

PMID- 25950386
TI  - TAp73 transcriptionally represses BNIP3 expression.
AB  - TAp73 is a tumor suppressor transcriptional factor, belonging to p53 family.
      Alteration of TAp73 in tumors might lead to reduced DNA damage response, cell
      cycle arrest and apoptosis. Carcinogen-induced TAp73(-/-) tumors display also
      increased angiogenesis, associated to hyperactivition of hypoxia inducible factor
      signaling. Here, we show that TAp73 suppresses BNIP3 expression, directly binding
      its gene promoter. BNIP3 is a hypoxia responsive protein, involved in a variety
      of cellular processes, such as autophagy, mitophagy, apoptosis and necrotic-like
      cell death. Therefore, through different cellular process altered expression of
      BNIP3 may differently contribute to cancer development and progression. We found
      a significant upregulation of BNIP3 in human lung cancer datasets, and we
      identified a direct association between BNIP3 expression and survival rate of
      lung cancer patients. Our data therefore provide a novel transcriptional target
      of TAp73, associated to its antagonistic role on HIF signaling in cancer, which
      might play a role in tumor suppression. 

PMID- 25950388
TI  - Immunohistochemical profiles of IDH1, MGMT and P53: practical significance for
      prognostication of patients with diffuse gliomas.
AB  - Genetic and epigenetic status, including mutations of isocitrate dehydrogenase
      (IDH) and TP53 and methylation of O(6) -methylguanine-DNA methyltransferase
      (MGMT), are associated with the development of various types of glioma and are
      useful for prognostication. Here, using routinely available histology sections
      from 312 patients with diffuse gliomas, we performed immunohistochemistry using
      antibodies specific for IDH1 mutation, MGMT methylation status, and aberrant p53
      expression to evaluate the possible prognostic significance of these features.
      With regard to overall survival (OS), univariate analysis indicated that an IDH1
      positive profile in patients with glioblastoma (GBM), anaplastic astrocytoma
      (AA), anaplastic oligoastrocytoma and oligodendroglioma, or a MGMT-negative
      profile in patients with GBM and AA were significantly associated with a
      favorable outcome. Multivariate analysis revealed that both profiles were
      independent factors influencing prognosis. The OS of patients with IDH1
      positive/MGMT-negative profiles was significantly longer than that of patients
      with negative/negative and negative/positive profiles. A p53 profile was not an
      independent prognostic factor. However, for GBM/AA patients with IDH1
      negative/MGMT-negative profiles, p53 overexpression was significantly associated
      with an unfavorable outcome. Thus, the immunohistochemical profiles of IDH1 and
      MGMT are of considerable significance in gliomas, and a combination of IDH1, MGMT
      and p53 profiles may be useful for prognostication of GBM/AA.

PMID- 25950389
TI  - Preoperative Versus Intraoperative Subpterygial Mitomycin C Injection for
      Prevention of Pterygium Recurrence.
AB  - PURPOSE: To evaluate postoperative outcome and recurrence rate after primary
      pterygium excision using preoperative versus intraoperative subpterygial
      Mitomycin C (MMC) injection. METHODS: Eighty-three eyes with primary pterygium
      were divided into 2 groups. Group A (35 eyes) was operated upon with pterygium
      excision 5 min after subpterygial injection of 0.1 mL 0.015% MMC in the same
      operative setting. Group B (48 eyes) was operated upon with pterygium excision 1
      month after subpterygial injection of the same amount and concentration of MMC as
      in group A. Pterygium regrowth over the cornea for 1 mm or more was considered as
      a recurrence. RESULTS: The mean follow-up was 30.66+/-4.48 months in group A and
      29.5+/-4.3 months in group B. In group A, the reported recurrence rate was 5.7%,
      while it was 4.2% in group B. No serious postoperative complications were
      reported. There was no statistically significant difference between both groups
      regarding the recurrence rate as well as the complication rate. CONCLUSION: Both
      techniques proved to be effective in reducing the recurrence rate after excision
      of primary nasal pterygium with minimal postoperative complications, with no need
      of a second surgery for patients in group A.

PMID- 25950390
TI  - Evolving Gaussian Mixture Models with Splitting and Merging Mutation Operators.
AB  - This paper describes the evolutionary split and merge for expectation
      maximization (ESM-EM) algorithm and eight of its variants, which are based on the
      use of split and merge operations to evolve Gaussian mixture models. Asymptotic
      time complexity analysis shows that the proposed algorithms are competitive with
      the state-of-the-art genetic-based expectation maximization (GA-EM) algorithm.
      Experiments performed in 35 data sets showed that ESM-EM can be computationally
      more efficient than the widely used multiple runs of EM (for different numbers of
      components and initializations). Moreover, a variant of ESM-EM free from critical
      parameters was shown to be able to provide competitive results with GA-EM, even
      when GA-EM parameters were fine-tuned a priori. 

PMID- 25950391
TI  - Toward Large-Scale Continuous EDA: A Random Matrix Theory Perspective.
AB  - Estimations of distribution algorithms (EDAs) are a major branch of evolutionary
      algorithms (EA) with some unique advantages in principle. They are able to take
      advantage of correlation structure to drive the search more efficiently, and they
      are able to provide insights about the structure of the search space. However,
      model building in high dimensions is extremely challenging, and as a result
      existing EDAs may become less attractive in large-scale problems because of the
      associated large computational requirements. Large-scale continuous global
      optimisation is key to many modern-day real-world problems. Scaling up EAs to
      large-scale problems has become one of the biggest challenges of the field. This
      paper pins down some fundamental roots of the problem and makes a start at
      developing a new and generic framework to yield effective and efficient EDA-type
      algorithms for large-scale continuous global optimisation problems. Our concept
      is to introduce an ensemble of random projections to low dimensions of the set of
      fittest search points as a basis for developing a new and generic divide-and
      conquer methodology. Our ideas are rooted in the theory of random projections
      developed in theoretical computer science, and in developing and analysing our
      framework we exploit some recent results in nonasymptotic random matrix theory. 

PMID- 25950392
TI  - Hybrid Evolutionary Approaches to Maximum Lifetime Routing and Energy Efficiency
      in Sensor Mesh Networks.
AB  - Mesh network topologies are becoming increasingly popular in battery-powered
      wireless sensor networks, primarily because of the extension of network range.
      However, multihop mesh networks suffer from higher energy costs, and the routing
      strategy employed directly affects the lifetime of nodes with limited energy
      resources. Hence when planning routes there are trade-offs to be considered
      between individual and system-wide battery lifetimes. We present a multiobjective
      routing optimisation approach using hybrid evolutionary algorithms to approximate
      the optimal trade-off between the minimum lifetime and the average lifetime of
      nodes in the network. In order to accomplish this combinatorial optimisation
      rapidly, our approach prunes the search space using k-shortest path pruning and a
      graph reduction method that finds candidate routes promoting long minimum
      lifetimes. When arbitrarily many routes from a node to the base station are
      permitted, optimal routes may be found as the solution to a well-known linear
      program. We present an evolutionary algorithm that finds good routes when each
      node is allowed only a small number of paths to the base station. On a real
      network deployed in the Victoria & Albert Museum, London, these solutions, using
      only three paths per node, are able to achieve minimum lifetimes of over 99% of
      the optimum linear program solution's time to first sensor battery failure. 

PMID- 25950393
TI  - A glossary of terms to assist the recognition and diagnosis of skin conditions
      associated with lower-limb chronic oedema.
AB  - There are a number of recognised skin conditions associated with chronic oedema,
      but the lack of agreed definitions and terminology often leads to poor
      recognition and a delay in treatment. Many patients are given a diagnostic
      'label' (e.g. varicose eczema) that often turns out to be incorrect, leading to
      an interruption in the patient pathway. Every skin condition can be described in
      a variety of ways and each professional group adheres to certain phrases and
      words that, within each discipline, are recognised, but when making onward
      referral or working between professions, it helps to have clear and concise
      definitions. This article aims is to standardise the terminology used to describe
      skin conditions of the lower limbs among health professionals, removing some of
      the discrepancy, and to develop a glossary to aid recognition, definition and
      hence diagnosis to ensure prompt and appropriate management is implemented. 

PMID- 25950394
TI  - Early lipoedema diagnosis and the RCGP e-learning course.
AB  - Frequently misdiagnosed as obesity, lipoedema is chronic condition involving an
      abnormal build-up of fat cells in the legs, thighs and buttocks that cannot be
      shifted by exercise or dieting. Estimated to affect up to 11% of the female
      population, the condition is widely unknown by health professionals. This means
      women typically wait for many years before diagnosis. This allows the condition
      to progress unchecked, resulting in unnecessary deterioration and the development
      of associated comorbidities, as well as significant pain and mental anguish. A
      free, 30-minute Royal College of General Practitioners (RCGP) e-learning course
      created in partnership with Lipoedema UK aims to rectify this situation by
      educating nurses, GPs and other health professionals on how to diagnose and
      manage lipoedema in primary care. This article aims to describe the condition of
      lipoedema, how to recognise/diagnose it, current treatment options and the
      findings of a 240-patient survey carried out by Lipoedema UK in 2013 that
      included documenting the difficulties for patients in obtaining a diagnosis as
      well as the mental and physical effects of the condition.

PMID- 25950395
TI  - Microfine toe caps: an innovative and cost-saving solution.
AB  - This article discusses the use of Microfine toe caps (Haddenham, UK) for the
      treatment of digit swelling. It will discuss the indications and
      contraindications of the device and offers some case studies where toe caps have
      been used in clinical practice. The use of the Microfine toe cap offers an
      alternative to toe bandaging, has many different applications and can be safe and
      time-saving to apply when used appropriately following a full and holistic
      assessment. 

PMID- 25950396
TI  - An interview with: a band 4 lymphoedema associate practitioner.

PMID- 25950398
TI  - Lymphoedema Support Network update.

PMID- 25950399
TI  - Getting it right for children.

PMID- 25950400
TI  - Treatment and outcomes of head and neck oedema referrals to a hospital-based
      lymphoedema service.
AB  - A retrospective review of all head and neck cancer-related lymphoedema (HNCRL)
      referrals from 1 October 2009 to 30 September 2013 was undertaken. HNCRL
      referrals significantly increased over a 4-year period. Lymphoedema clinic
      records were manually examined for the presentation of HNCRL, treatments
      provided, and outcomes. Some 207 HNCRL referrals were received, increasing by
      251% from 2009 to 2013. A total of 110 men and 50 women were assessed and treated
      over the 4 years; 67% were discharged, 26% continued treatment/monitoring by
      clinic; 8% are deceased. The average time to discharge reduced from 16 to 5
      months. From the results, it seems that self-management with exercise and counter
      pressure/compression is very effective and the requirement for manual lymph
      drainage is reduced. There is increased patient engagement with effective self
      care. Provision of appropriate education and information facilitated simple,
      effective self-management. This reduced treatment time, shortened time to
      discharge and released valuable practitioner time to treat patients with complex
      oedema.

PMID- 25950401
TI  - Isolation and characterization of inulin with a high degree of polymerization
      from roots of Stevia rebaudiana (Bert.) Bertoni.
AB  - The polysaccharide inulin has great importance in the food and pharmaceutical
      industries. The degree of polymerization (DP) of inulin influences important
      properties, such as, solubility, thermal stability, sweetness power and prebiotic
      activity. Molecules with a high degree of polymerization are obtained through
      physical techniques for enrichment of the inulin chains because they are not
      commonly obtained from plants extract. Gas chromatography/Mass Spectrometry and
      (1)H Nuclear Magnetic Resonance analysis showed that inulin from Stevia
      rebaudiana roots has a degree of polymerization (DPn 28) higher than the value of
      DPn 12-15 for inulins from other plant species. Furthermore, the methodology of
      freeze/thaw to enrich the chains allowed us to increase the DP, similarly to
      other methodologies used for the enrichment of inulin chains. The prebiotic
      assays confirm that inulin from S. rebaudiana has a high DP. The combined use of
      these molecules with low degree of polymerization fructans seems to be
      advantageous to prolong the prebiotic effect in the colon. Our results suggest
      that S. rebaudiana roots are a promising source of high degree polymerization
      inulins. 

PMID- 25950402
TI  - A Remarkably Complex Supramolecular Hydrogen-Bonded Decameric Capsule Formed from
      an Enantiopure C2-Symmetric Monomer by Solvent-Responsive Aggregation.
AB  - The formation of an unprecedented decameric capsule in carbon disulfide, held
      together by the combination of double and triple hydrogen bonds between
      isocytosine units embedded in an enantiomerically pure bicyclic framework is
      reported. The aggregation occurs via symmetry breaking of the enantiopure
      intrinsically C2-symmetric monomer brought about by solvent, induced
      tautomerization of the hydrogen-bonding unit. We show that the topology of the
      aggregate is responsive to the solvent in which the assembly takes place. In this
      study we demonstrate that in carbon disulfide the chiral decameric cavity
      aggregate consisting of three forms of the same monomer, differing in their
      hydrogen bonding to each other is selectively formed, representing a tube-like
      structure capped with two C2-symmetric monomers. The large cylindrical cavity
      produced selectively accommodates one partially solvated C60 molecule, and
      molecular dynamic simulations revealed the special role of the solvent in the
      inclusion mechanism. The strategy described herein represents the first step
      toward the creation of a new class of hydrogen-bonded tubular objects from only
      one small symmetric building block by solvent-responsive aggregation. 

PMID- 25950403
TI  - Amino-Functionalized Multiwalled Carbon Nanotubes Lead to Successful Ring-Opening
      Polymerization of Poly(epsilon-caprolactone): Enhanced Interfacial Bonding and
      Optimized Mechanical Properties.
AB  - In this work, the synthesis, structural characteristics, interfacial bonding, and
      mechanical properties of poly(epsilon-caprolactone) (PCL) nanocomposites with
      small amounts (0.5, 1.0, and 2.5 wt %) of amino-functionalized multiwalled carbon
      nanotubes (f-MWCNTs) prepared by ring-opening polymerization (ROP) are reported.
      This method allows the creation of a covalent-bonding zone on the surface of
      nanotubes, which leads to efficient debundling and therefore satisfactory
      dispersion and effective load transfer in the nanocomposites. The high covalent
      grafting extent combined with the higher crystallinity provide the basis for a
      significant enhancement of the mechanical properties, which was detected in the
      composites with up to 1 wt % f-MWCNTs. Increasing filler concentration encourages
      intrinsic aggregation forces, which allow only minor grafting efficiency and
      poorer dispersion and hence inferior mechanical performance. f-MWCNTs also cause
      a significant improvement on the polymerization reaction of PCL. Indeed, the in
      situ polymerization kinetics studies reveal a significant decrease in the
      reaction temperature, by a factor of 30-40  degrees C, combined with accelerated
      the reaction kinetics during initiation and propagation and a drastically reduced
      effective activation energy.

PMID- 25950404
TI  - Molecular trajectories provide signatures of protein clustering and crowding at
      the oil/water interface.
AB  - Using high throughput single-molecule total internal reflection fluorescence
      microscopy (TIRFM), we have acquired molecular trajectories of bovine serum
      albumin (BSA) and hen egg white lysozyme during protein layer formation at the
      silicone oil-water interface. These trajectories were analyzed to determine the
      distribution of molecular diffusion coefficients, and for signatures of molecular
      crowding/caging, including subdiffusive motion and temporal anticorrelation of
      the instantaneous velocity vector. The evolution of these properties with aging
      time of the interface was compared with dynamic interfacial tension measurements.
      For both lysozyme and BSA, we observed an overall slowing of protein objects, the
      onset of both subdiffusive and anticorrelated motion (associated with crowding),
      and a decrease in the interfacial tension with aging time. For lysozyme, all of
      these phenomena occurred virtually simultaneously, consistent with a homogeneous
      model of layer formation that involves gradual crowding of weakly interacting
      proteins. For BSA, however, the slowing occurred first, followed by the
      signatures of crowding/caging, followed by a decrease in interfacial tension,
      consistent with a heterogeneous model of layer formation involving the formation
      of protein clusters. The application of microrheological methods to single
      molecule trajectories described here provides an unprecedented level of
      mechanistic interpretation of interfacial events that occurred over a wide range
      of interfacial protein coverage. 

PMID- 25950405
TI  - Cu(I)-Catalyzed Cross-Coupling of Terminal Alkynes with Trifluoromethyl Ketone N
      Tosylhydrazones: Access to 1,1-Difluoro-1,3-enynes.
AB  - C-C Bond formation and beta-F elimination have been achieved in a Cu(I)-catalyzed
      cross-coupling reaction of terminal alkynes and trifluoromethyl ketone N
      tosylhydrazones. The reaction represents an efficient synthesis of 1,1-difluoro
      1,3-enyne derivatives. Mechanistically, the migratory insertion of the copper
      carbene intermediate leads to the C-C bond formation, which is followed by C-F
      bond cleavage. 

PMID- 25950406
TI  - The reproductive toxicity on the rotifer Brachionus plicatilis induced by BDE-47
      and studies on the effective mechanism based on antioxidant defense system
      changes.
AB  - 2,2',4,4'-Tetrabromodiphenyl ether (BDE-47), a low-brominated Tetra-BDE that is
      widely distributed in the marine ecosystem, was selected to investigate the
      reproductive toxicity on the rotifer, Brachionus plicatilis, and the possible
      mechanism based on antioxidant defense system changes were studied. The results
      showed the following: (1) A low concentration of BDE-47 had a slight effect on
      the egg production of individual females and the egg production rate (EPR) of the
      population. In fact, BDE-47 exerted reproductive inhibition effects in a time-
      and concentration-dependent manner. The obtained life tables indicated that BDE
      47 at a high concentration prolonged the generation time, whereas low and
      moderate concentrations of BDE-47 had the opposite effects. BDE-47 at a medium
      concentration significantly decreased the life expectancy and net reproductive
      rate (P<0.05). Additionally, a high concentration of BDE-47 markedly decreased
      the net reproductive rate and intrinsic increase rate (P<0.05). The ultra
      structure of the ovary showed that BDE-47 severely damaged the ovary. (2) BDE-47
      stress elevated the ROS level in B. plicatilis. The GST activity was induced
      significantly by the low concentration of BDE-47 and inhibited by the highest
      concentration tested. The GPx activity and GSH content were significant decreased
      in all the tested groups, and GR activity was induced. GST and GSH appeared to be
      sensitive to oxidative stress, and all of the glutathione-related enzymes were
      found to play an important role in maintaining the antioxidant/pro-oxidant
      balance based on Pearson's correlation analysis. The results indicated that BDE
      47 causes reproductive toxicity in B. plicatilis and that the ROS-mediated
      pathway is responsible for the observed toxicity. 

PMID- 25950407
TI  - Fate of antibiotic resistant cultivable heterotrophic bacteria and antibiotic
      resistance genes in wastewater treatment processes.
AB  - Antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) are
      emerging contaminants of environmental concern. Heterotrophic bacteria in
      activated sludge have an important role in wastewater treatment plants (WWTPs).
      However, the fate of cultivable heterotrophic ARB and ARGs in WWPTs process
      remains unclear. In the present study, we investigated the antibiotic-resistant
      phenotypes of cultivable heterotrophic bacteria from influent and effluent water
      of three WWTPs and analysed thirteen ARGs in ARB and in activated sludge from
      anoxic, anaerobic and aerobic compartments. From each influent or effluent sample
      of the three plants, 200 isolates were randomly tested for susceptibility to 12
      antibiotics. In these samples, between 5% and 64% isolates showed resistance to
      >9 antibiotics and the proportion of >9-drug-resistant bacteria was lower in
      isolates from effluent than from influent. Eighteen genera were identified in 188
      isolates from influent (n=94) and effluent (n=94) of one WWTP. Six genera
      (Aeromonas, Bacillus, Lysinibacillus, Microbacterium, Providencia, and
      Staphylococcus) were detected in both influent and effluent samples. Gram
      negative and -positive isolates dominated in influent and effluent, respectively.
      The 13 tetracycline-, sulphonamide-, streptomycin- and beta-lactam-resistance
      genes were detected at a higher frequency in ARB from influent than from
      effluent, except for sulA and CTX-M, while in general, the abundances of ARGs in
      activated sludge from two of the three plants were higher in aerobic compartments
      than in anoxic ones, indicating abundant ARGs exit in the excess sledges and/or
      in uncultivable bacteria. These findings may be useful for elucidating the effect
      of WWTP on ARB and ARGs. 

PMID- 25950408
TI  - Behavioral and biochemical responses in freshwater fish Carassius auratus exposed
      to sertraline.
AB  - Sertraline is one of the most commonly prescribed selective serotonin reuptake
      inhibitors and is frequently detected in the aquatic environment. However,
      knowledge regarding relationships among molecular or biochemical endpoints
      involved in modes of action (MOAs) of sertraline and ecologically important
      behavioral responses of fish is insufficient. The present study aimed to
      investigate the bioconcentration and possible adverse outcomes pathways (AOPs) in
      crucian carp (Carassius auratus) exposed to various concentrations of sertraline
      (4.36, 21.3 and 116 MUg L(-1)) for 7 d. Bioconcentration factor values were in
      the range of 19.5-626 in liver, 6.94-285 in brain, 4.01-146 in gill and 0.625
      43.1 in muscle during the entire period of exposure. Liver superoxide dismutase
      (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase
      (GST) activities and brain acetylcholinesterase (AChE) activity were selected as
      biochemical endpoints associated with MOAs. Swimming activity, shoaling, feeding
      rate and food consumption were determined to assess behavioral responses. Fish
      plasma levels of sertraline exceeding human therapeutic doses were also predicted
      from external exposure concentrations. Significant enhancements in CAT, GPx, AChE
      and swimming activities and decreases in shoaling tendency, feeding rate and food
      consumption were observed when fish plasma levels exceeded human therapeutic
      thresholds. Shoaling, feeding rate and food consumption were correlated with the
      activities of SOD, CAT and GST. A significant positive correlation between
      swimming activity and AChE activity was also observed. As such, our study
      provides important AOPs linking biochemical responses with ultimate ecologically
      relevant behavioral endpoints.

PMID- 25950409
TI  - Potential human health risks from toxic metals via mangrove snail consumption and
      their ecological risk assessments in the habitat sediment from Peninsular
      Malaysia.
AB  - Samples of mangrove snails Nerita lineata and surface sediments were collected
      from nine geographical sampling sites in Peninsular Malaysia to determine the
      concentrations of eight metals. For the soft tissues, the ranges of metal
      concentrations (MUg g(-1) dry weight (dw)) were 3.49-9.02 for As, 0.69-6.25 for
      Cd, 6.33-25.82 for Cu, 0.71-6.53 for Cr, 221-1285 for Fe, 1.03-50.47 for Pb, and
      102.7-130.7 for Zn while Hg as 4.00-64.0 MUg kg(-1) dw(-1). For sediments, the
      ranges were 21.81-59.49 for As, 1.11-2.00 for Cd, 5.59-28.71 for Cu, 18.93-62.91
      for Cr, 12973-48916 for Fe, 25.36-172.57 for Pb, and 29.35-130.34 for Zn while
      for Hg as 2.66-312 MUg kg(-1) dw(-1). To determine the ecological risks on the
      surface habitat sediments, sediment quality guidelines (SQGs), the geochemical
      indices, and potential ecological risk index (PERI) were used. Based on the SQGs,
      all the metals investigated were most unlikely to cause any adverse effects.
      Based on geoaccumulation index and enrichment factor, the sediments were also not
      polluted by the studied metals. The PERI values based on As, Cd, Cu, Cr, Hg, Pb
      and Zn in this study were found as 'low ecological risk'. In order to assess the
      potential health risks, the estimated daily intakes (EDI) of snails were found to
      be all lower than the RfD guidelines for all metals, except for Pb in some sites
      investigated. Furthermore, the calculated target hazard quotients (THQ) were
      found to be less than 1. However, the calculated total target hazard quotients
      (TTHQ) from all sites were found to be more than 1 for high level consumers
      except KPPuteh. Therefore, moderate amount of intake is advisable to avoid human
      health risks to the consumers.

PMID- 25950410
TI  - Subchronic and chronic developmental effects of copper oxide (CuO) nanoparticles
      on Xenopus laevis.
AB  - Metal oxide nanoparticles, such as copper oxide (CuO), are mass produced for use
      in a variety of products like coatings and ceramics. Acute exposure to CuO
      nanoparticles has caused toxicity to many aquatic organisms, yet there is no
      information on the effect of prolonged CuO nanomaterial exposures. This study
      examined effects of chronic exposure to CuO nanoparticles on Xenopus laevis
      growth and development. Experiments included a 14 d subchronic exposure and a 47
      d chronic exposure throughout metamorphosis. The subchronic exposure caused
      mortality in all tested CuO concentrations, and significant growth effects
      occurred after exposure to 2.5 mg L(-1) CuO. Chronic exposure to 0.3 mg L(-1) CuO
      elicited significant mortality and affected the rate of metamorphosis. Exposure
      to lower concentrations of CuO stimulated metamorphosis and growth, indicating
      that low dose exposure can have hormetic effects.

PMID- 25950411
TI  - Effects of an environmentally relevant temporal application scheme of low
      herbicide concentrations on larvae of two anuran species.
AB  - Cultivation of herbicide-tolerant crops involves repeated applications of the
      complementary herbicide throughout the growing season, while in conventional corn
      production, herbicide application is restricted to the beginning of cultivation.
      Repeated application of herbicides increases both the likelihood an organism will
      be exposed to the herbicide and the concentration it may be exposed to. We
      examined effects of short and pulsed exposure of the cycloxydim-based herbicide
      formulation Focus(r) Ultra at doses close to the calculated LC5 (0.01 and 0.5 mg
      a.i. L(-1)) and LC10 values (0.05 and 1.0 mg a.i. L(-1)) on early premetamorphic
      and prometamorphice larvae of two anuran model organisms, Xenopus laevis and
      Discoglossus scovazzi. In addition, larvae were repeatedly exposed, i.e. at all
      considered developmental stages. The herbicide did not induce effects on body
      size at and time to metamorphosis or increase deformation rates in both species.
      Exposure to calculated LC5 values did not increase mortality or cause clinical
      signs in both species. At calculated LC10 values, narcotic effects were seen in
      all developmental stages. There was no clear evidence of developmental-specific
      mortality. Metamorphic success was independent of time point and duration of
      application in X. laevis. Only repeated exposure significantly increased
      mortality at metamorphosis in D. scovazzi. Narcosis may result in increased
      mortality under field conditions due to rise of predation risk. Different
      sensitivity of the test species to the compound was attributed to their
      physiological properties. Different filtering rates were understood as an
      accompanying factor influencing exposition.

PMID- 25950413
TI  - Special issue: multiscale biomechanics.

PMID- 25950414
TI  - Physical chemistry of climate metrics.

PMID- 25950412
TI  - Acute toxicity of benzophenone-type UV filters for Photobacterium phosphoreum and
      Daphnia magna: QSAR analysis, interspecies relationship and integrated
      assessment.
AB  - The hazardous potential of benzophenone (BP)-type UV filters is becoming an issue
      of great concern due to the wide application of these compounds in many personal
      care products. In the present study, the toxicities of BPs to Photobacterium
      phosphoreum and Daphnia magna were determined. Next, density functional theory
      (DFT) and comparative molecular field analysis (CoMFA) descriptors were used to
      obtain more detailed insight into the structure - activity relationships and to
      preliminarily discuss the toxicity mechanism. Additionally, the sensitivities of
      the two organisms to BPs and the interspecies toxicity relationship were
      compared. Moreover, an approach for providing a global index of the environmental
      risk of BPs to aquatic organisms is proposed. The results demonstrated that the
      mechanism underlying the toxicity of BPs to P. phosphoreum is primarily related
      to their electronic properties, and the mechanism of toxicity to D. magna is
      hydrophobicity. Additionally, D. magna was more sensitive than P. phosphoreum to
      most of the BPs, with the exceptions of the polyhydric BPs. Moreover, comparisons
      with published data revealed a high interspecies correlation coefficient among
      the experimental toxicity values for D. magna and Dugesia japonica. Furthermore,
      hydrophobicity was also found to be the most important descriptor of integrated
      toxicity. This investigation will provide insight into the toxicity mechanisms
      and useful information for assessing the potential ecological risk of BP-type UV
      filters. 

PMID- 25950415
TI  - Impact of Protease on Ultraviolet Photodissociation Mass Spectrometry for Bottom
      up Proteomics.
AB  - Recent mass spectrometric studies have reported enhanced proteome coverage by
      employing multiple proteases or by using multiple or alternative activation
      methods such as electron-transfer dissociation in combination with collisional
      activated dissociation (CAD). In this study the use of 193 nm ultraviolet
      photodissociation for the analysis of thousands of Halobacterium salinarum
      peptides generated by four proteases (trypsin, LysC, GluC, and chymotrypsin) was
      evaluated in comparison with higher energy CAD (HCD). Proteins digested by
      trypsin resulted in greater sequence coverage for HCD over UVPD. LysC digestion
      resulted in similar sequence coverages for UVPD and HCD; however, for proteins
      digested by GluC and chymotrypsin 5-10% more sequence coverage on average was
      achieved by UVPD. HCD resulted in more peptide identifications (at 1% false
      discovery rate) for trypsin (4356 peptides by HCD versus 3907 peptides by UVPD),
      whereas UVPD identified greater numbers of peptides for LysC digests (1033
      peptides by UVPD versus 844 HCD), chymotrypsin digests (3219 peptides for UVPD
      versus 2921 for HCD), and GluC digests (2834 peptides for UVPD and 2393 for HCD)
      and correspondingly greater numbers of proteins. 

PMID- 25950416
TI  - Effective nitrogen removal and recovery from dewatered sewage sludge using a
      novel integrated system of accelerated hydrothermal deamination and air
      stripping.

PMID- 25950417
TI  - Association of Disorganization of Retinal Inner Layers With Vision After
      Resolution of Center-Involved Diabetic Macular Edema.
AB  - IMPORTANCE: Macular edema (ME) prognosis and treatment response vary according to
      the underlying abnormalities. Biomarkers of visual acuity (VA) improvement could
      influence management decisions in different types of ME. OBJECTIVE: To
      investigate whether disorganization of retinal inner layers (DRIL) and other
      spectral-domain optical coherence tomography (SD-OCT)-derived variables are
      associated with subsequent VA after ME resolution in both nondiabetic and
      diabetic ME. DESIGN, SETTING, AND PARTICIPANTS: A retrospective, longitudinal
      cohort study in which Snellen VA testing and SD-OCT macular imaging were
      performed, was conducted at a tertiary referral eye center for retinal diseases.
      The medical records of all patients with ME from December 1, 2010, to December
      31, 2012, were reviewed. The date of the last follow-up was June 1, 2013.
      Participants included 55 patients (70 eyes) with center-involved ME that had
      resolved during an 8-month period. Patients were grouped based on the source of
      ME (diabetic vs nondiabetic). Exclusion criteria included significant media
      opacity interfering with good-quality SD-OCT image acquisition. Masked graders
      analyzed the central 1500-MUm macular region for changes, including cysts, DRIL
      length and extent, and outer retinal layers disruption. Intragrader and
      intergrader agreement Spearman rank correlation coefficients ranged from 0.70 to
      0.93 for quantitative measurement, and kappa values ranged from 0.88 to 1.00 for
      qualitative grading. MAIN OUTCOMES AND MEASURES: Visual acuity and morphologic
      changes measured on SD-OCT. RESULTS: In both groups, VA after ME resolution
      correlated with baseline VA. In diabetic ME involving a multivariable model
      including baseline VA and DRIL, total length was associated with subsequent VA as
      determined by a parameter estimate (PE) of 0.0003 (95% CI, 0-0.0006) (P = .03).
      The VA change during the 8-month period, after adjusting for baseline VA, was
      best associated with DRIL change (PE, 0.0002 [95% CI, 0-0.0003]; P = .04).
      Participants whose DRIL resolved, both early and late, showed improvement in
      their VA deficit at 8 months (least squares mean [SE], 41.3 [28.5] and 40.9
      [37.5], respectively) compared with nonresolvers, whether inconsistent or
      persistent, whose VA worsened. After adjustment for baseline VA, eyes with
      persistent DRIL showed the largest difference in VA deficit compared with those
      with no baseline DRIL (-89.6 [27.2] vs 49.7 [19.6], respectively; P = .006).
      CONCLUSIONS AND RELEVANCE: The presence of DRIL at baseline and its resolution
      pattern may be associated with subsequent VA after resolution of center-involved
      diabetic ME.

PMID- 25950419
TI  - Lateral Size-Dependent Spontaneous and Stimulated Emission Properties in
      Colloidal CdSe Nanoplatelets.
AB  - Here, we systematically investigated the spontaneous and stimulated emission
      performances of solution-processed atomically flat quasi-2D nanoplatelets (NPLs)
      as a function of their lateral size using colloidal CdSe core NPLs. We found that
      the photoluminescence quantum efficiency of these NPLs decreases with increasing
      lateral size while their photoluminescence decay rate accelerates. This strongly
      suggests that nonradiative channels prevail in the NPL ensembles having extended
      lateral size, which is well-explained by the increasing number of the defected
      NPL subpopulation. In the case of stimulated emission the role of lateral size in
      NPLs influentially emerges both in the single- and two-photon absorption (1PA and
      2PA) pumping. In the amplified spontaneous emission measurements, we uncovered
      that the stimulated emission thresholds of 1PA and 2PA exhibit completely
      opposite behavior with increasing lateral size. The NPLs with larger lateral
      sizes exhibited higher stimulated emission thresholds under 1PA pumping due to
      the dominating defected subpopulation in larger NPLs. On the other hand,
      surprisingly, larger NPLs remarkably revealed lower 2PA-pumped amplified
      spontaneous emission thresholds. This is attributed to the observation of a
      "giant" 2PA cross-section overwhelmingly growing with increasing lateral size and
      reaching record levels higher than 10(6) GM, at least an order of magnitude
      stronger than colloidal quantum dots and rods. These findings suggest that the
      lateral size control in the NPLs, which is commonly neglected, is essential to
      high-performance colloidal NPL optoelectronic devices in addition to the vertical
      monolayer control. 

PMID- 25950418
TI  - Effects of Oropharyngeal Exercises on Snoring: A Randomized Trial.
AB  - BACKGROUND: Snoring is extremely common in the general population and may
      indicate OSA. However, snoring is not objectively measured during
      polysomnography, and no standard treatment is available for primary snoring or
      when snoring is associated with mild forms of OSA. This study determined the
      effects of oropharyngeal exercises on snoring in minimally symptomatic patients
      with a primary complaint of snoring and diagnosis of primary snoring or mild to
      moderate OSA. METHODS: Patients were randomized for 3 months of treatment with
      nasal dilator strips plus respiratory exercises (control) or daily oropharyngeal
      exercises (therapy). Patients were evaluated at study entry and end by sleep
      questionnaires (Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index) and
      full polysomnography with objective measurements of snoring. RESULTS: We studied
      39 patients (age, 46 +/- 13 years; BMI, 28.2 +/- 3.1 kg/m2; apnea-hypopnea index
      (AHI), 15.3 +/- 9.3 events/h; Epworth Sleepiness Scale, 9.2 +/- 4.9; Pittsburgh
      Sleep Quality Index, 6.4 +/- 3.3). Control (n = 20) and therapy (n = 19) groups
      were similar at study entry. One patient from each group dropped out. Intention
      to-treat analysis was used. No significant changes occurred in the control group.
      In contrast, patients randomized to therapy experienced a significant decrease in
      the snore index (snores > 36 dB/h), 99.5 (49.6-221.3) vs 48.2 (25.5-219.2); P =
      .017 and total snore index (total power of snore/h), 60.4 (21.8-220.6) vs 31.0
      (10.1-146.5); P = .033. CONCLUSIONS: Oropharyngeal exercises are effective in
      reducing objectively measured snoring and are a possible treatment of a large
      population suffering from snoring. TRIAL REGISTRY: ClinicalTrials.gov; No.:
      NCT01636856; URL: www.clinicaltrials.gov.

PMID- 25950421
TI  - Comparison of Five Kinematic-Based Identification Methods   of Foot Contact
      Events During Treadmill Walking and Running   at Different Speeds.
AB  - This study involved a comparison of 5 kinematic-based algorithms to detect heel
      strike (HS) and toe-off (TO) events during human locomotion at different speeds.
      The objective was to assess how different running and walking speeds affect
      contact event determination during treadmill locomotion. Thirty male runners
      performed walking at 5 km/h and running at 9, 11, and 13 km/h on a treadmill. A
      kinematic system was used to capture the trajectories of 2 retroreflective
      markers placed at the subject's right heel and second metatarsal. A footswitch
      device was used to determine the "true" times of HS and TO compared with 5
      kinematic-based algorithms. The results of the current study illustrated that
      speed influences the HS error in the vertical position and horizontal velocity
      algorithms, and the TO error in the vertical position and horizontal velocity
      algorithms. This difference was found in the transition from walking to running;
      however, higher running speeds did not affect the error estimation. Higher
      accuracy was found with combined algorithms, namely, one using vertical
      acceleration and position and another using horizontal and vertical position with
      no influence from different locomotion speeds. Therefore, these algorithms are
      recommended in studies where speed is self-selected because they work well for a
      broad range of locomotion velocities.

PMID- 25950422
TI  - Thermally Responsive Hydrogel Blends: A General Drug Carrier Model for Controlled
      Drug Release.
AB  - Thermally responsive hydrogels have drawn significant research attention recently
      because of their simple use as drug carrier at human body temperature. Here we
      design a hybrid hydrogel that incorporates a hydrophilic polymer,
      polyethyleneimine (PEI), into the thermally responsive hydrogel poly(N
      isopropylacrylamide) (PNIPAm), as a general drug carrier model for controlled
      drug release. In this work, on one hand, PEI modifies the structure and the size
      of the pores in the PNIPAm hydrogel. On the other hand, PEI plays an important
      role in tuning the water content in the hydrogel and controls the water release
      rate of the hydrogel below the lower critical solution temperature (LCST),
      resulting in a tunable release rate of the drugs at human body temperature (37 
      degrees C). Different release rates are shown as different amounts of PEI are
      incorporated. PEI controls the release rate, dependent on the charge
      characteristics of the drugs. The hydrogel blends described in this work extend
      the concept of a general drug carrier for loading both positively and negatively
      charged drugs, as well as the controlled release effect. 

PMID- 25950420
TI  - Flow-perfusion bioreactor system for engineered breast cancer surrogates to be
      used in preclinical testing.
AB  - There is a need for preclinical testing systems that predict the efficacy, safety
      and pharmacokinetics of cancer therapies better than existing in vitro and in
      vivo animal models. An approach to the development of predictive in vitro systems
      is to more closely recapitulate the cellular and spatial complexity of human
      cancers. One limitation of using current in vitro systems to model cancers is the
      lack of an appropriately large volume to accommodate the development of this
      complexity over time. To address this limitation, we have designed and
      constructed a novel flow-perfusion bioreactor system that can support large
      volume, engineered tissue comprised of multicellular cancer surrogates by
      modifying current microfluidic devices. Key features of this technology are a
      three-dimensional (3D) volume (1.2 cm3 ) that has greater tissue thickness than
      is utilized in existing microfluidic systems and the ability to perfuse the
      volume, enabling the development of realistic tumour geometry. The constructs
      were fabricated by infiltrating porous carbon foams with an extracellular matrix
      (ECM) hydrogel and engineering through-microchannels. The carbon foam
      structurally supported the hydrogel and microchannel patency for up to 161 h. The
      ECM hydrogel was shown to adhere to the carbon foam and polydimethylsiloxane flow
      chamber, which housed the hydrogel-foam construct, when surfaces were coated with
      glutaraldehyde (carbon foam) and nitric acid (polydimethylsiloxane).
      Additionally, the viability of breast cancer cells and fibroblasts was higher in
      the presence of perfused microchannels in comparison to similar preparations
      without microchannels or perfusion. Therefore, the flow-perfusion bioreactor
      system supports cell viability in volume and stromal contexts that are
      physiologically-relevant. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 25950423
TI  - Aerogen Bonding Interaction: A New Supramolecular Force?
AB  - We report evidence of the favorable noncovalent interaction between a covalently
      bonded atom of Group 18 (known as noble gases or aerogens) and a negative site,
      for example, a lone pair of a Lewis base or an anion. It involves a region of
      positive electrostatic potential (sigma-hole), therefore it is a totally new and
      unexplored sigma-hole-based interaction, namely aerogen bonding. We demonstrate
      for the first time the existence of sigma-hole regions in aerogen derivatives by
      means of high-level ab initio calculations. In addition, several crystal
      structures retrieved from the Cambridge Structural Database (CSD) give
      reliability to the calculations. Energetically, aerogen bonds are comparable to
      hydrogen bonds and other sigma-hole-based interactions but less directional. They
      are expected to be important in xenon chemistry.

PMID- 25950424
TI  - Surgical interventions for treating acute fractures or non-union of the middle
      third of the clavicle.
AB  - BACKGROUND: This review covers two conditions: acute clavicle fractures and non
      union resulting from failed fracture healing. Clavicle (collarbone) fractures
      account for around 4% of all fractures. While treatment for these fractures is
      usually non-surgical, some types of clavicular fractures, as well as non-union of
      the middle third of the clavicle, are often treated surgically. This is an update
      of a Cochrane review first published in 2009. OBJECTIVES: To evaluate the effects
      (benefits and harms) of different methods of surgical treatment for acute
      fracture or non-union of the middle third of the clavicle. SEARCH METHODS: We
      searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register
      (27 June 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (The
      Cochrane Library 2014, Issue 5), MEDLINE (1966 to June week 3 2014), EMBASE (1988
      to 2014 week 25), LILACS (1982 to 27 June 2014), trial registries and reference
      lists of articles. We applied no language or publication restrictions. SELECTION
      CRITERIA: We considered randomised and quasi-randomised controlled trials
      evaluating any surgical intervention for treating people with fractures or non
      union of the middle third of the clavicle. The primary outcomes were shoulder
      function or disability, pain and treatment failure (measured by the number of
      participants who had undergone or were being considered for a non-routine
      secondary surgical intervention for symptomatic non-union, malunion or other
      complications). DATA COLLECTION AND ANALYSIS: Two review authors selected
      eligible trials, independently assessed risk of bias and cross-checked data.
      Where appropriate, we pooled results of comparable trials. MAIN RESULTS: We
      included seven trials in this review with 398 participants. Four trials were new
      in this update.The four new trials (160 participants) compared intramedullary
      fixation with open reduction and internal fixation with plate for treating acute
      middle third clavicle fractures in adults. Low quality evidence from the four
      trials indicated that intramedullary fixation did not result in a clinically
      important improvement in upper arm function (despite a statistically significant
      difference in its favour: standardised mean difference 0.45, 95% confidence
      interval (CI) 0.08 to 0.81; 120 participants, three trials) at long term follow
      up of six months or more. Very low quality evidence indicated little difference
      between intramedullary fixation and plate fixation in pain (one trial), treatment
      failure resulting in non-routine surgery (2/68 with intramedullary fixation vs.
      3/65 with plate fixation; risk ratio 0.69, 95% CI 0.16 to 2.97, four trials) or
      time to clinical fracture consolidation (three trials). There was very low
      quality evidence of a lower incidence of participants with adverse events (mainly
      infection, poor cosmetic result and symptomatic hardware) in the intramedullary
      fixation group (18/68 with intramedullary fixation vs. 27/65 with plate fixation;
      RR 0.64, 95% CI 0.39 to 1.03) but the CI of the pooled results also included the
      small possibility of a lower incidence in the plate fixation group. None of the
      four trials reported on quality of life or return to previous activities.
      Evidence is pending from two ongoing trials, with planned recruitment of 245
      participants, testing this comparison.There was low or very low quality evidence
      from three small trials, each testing a different comparison. The three trials
      had design features that carried a high risk of bias, potentially limiting the
      reliability of their findings. Low-contact dynamic compression plates appeared to
      be associated with significantly better upper-limb function throughout the year
      following surgery, earlier fracture union and return to work, and a reduced
      incidence of implant-associated symptoms when compared with a standard dynamic
      compression plate in 36 adults with symptomatic non-union of the middle third of
      the clavicle. One quasi-randomised trial (69 participants) compared Knowles pin
      versus a plate for treating middle third clavicle fractures or non-union. Knowles
      pins appeared to be associated with lower pain levels and use of postoperative
      analgesics and a reduced incidence of implant-associated symptoms. One study (133
      participants) found that a three-dimensional technique for fixation with a
      reconstruction plate was associated with a significantly lower incidence of
      symptomatic delayed union than a standard superior position surgical approach.
      Evidence is pending from two ongoing trials, with planned recruitment of 130
      participants, comparing anterior versus superior plates for acute fractures.
      AUTHORS' CONCLUSIONS: There is very limited and low quality evidence available
      from randomised controlled trials regarding the effectiveness of different
      methods of surgical fixation of fractures and non-union of the middle third of
      the clavicle. The evidence from four ongoing trials is likely to inform practice
      for the comparisons of intramedullary versus plate fixation and anterior versus
      superior plates for acute fractures in a future update. Further randomised trials
      are warranted, but in order to optimise research effort, these should be preceded
      by research that aims to identify priority questions.

PMID- 25950425
TI  - The effects of preoperative oral pregabalin and perioperative intravenous
      lidocaine infusion on postoperative morphine requirement in patients undergoing
      laparatomy.
AB  - OBJECTIVES: To evaluate and compare the effects of preoperative oral pregabalin
      and perioperative intravenous lidocaine infusion on postoperative morphine
      requirement, adverse effects, patients' satisfaction, mobilization, time to first
      defecation and time to discharge in patients undergoing laparotomy. METHODS:
      Eighty patients (18 to 65 years of age) undergoing elective laparotomy were
      randomly divided into four groups (n=20 in each group): group C, placebo capsules
      and normal saline infusion perioperatively (control); group L, placebo capsules
      and lidocaine 1 mg/kg intravenous bolus dose followed by 2 mg/kg/h infusion until
      skin closure; group P, 150 mg oral pregabalin and normal saline infusion
      perioperatively; and group PL, 150 mg oral pregabalin and lidocaine 2 mg/kg/h
      infusion until skin closure. Hemodynamic parameters, visual analogue scale (VAS)
      scores, analgesic consumption, side effects, time to mobilization, time to first
      defecation, time to discharge and patients' satisfaction were recorded. RESULTS:
      VAS scores of group L, group P and group PL were lower than group C (P<0.05).
      Morphine consumption of group P and group PL was lower than group C (P<0.05).
      Incidence of nausea in group C was higher than group L and group PL. Time to
      first defecation and mobilization were shorter in group L and group PL compared
      with group C (P<0.05). CONCLUSION: Preoperative oral pregabalin and perioperative
      intravenous lidocaine infusion decreased postoperative VAS scores. Preoperative
      oral pregabalin decreased morphine requirement and perioperative intravenous
      lidocaine infusion hastened gastrointestinal motility and mobilization, and
      decreased the incidence of nausea in patients undergoing laparotomy. Therefore,
      preoperative pregabalin with or without lidocaine provides superior pain relief
      in patients undergoing laparatomy.

PMID- 25950426
TI  - Cage-like copper(II) silsesquioxanes: transmetalation reactions and structural,
      quantum chemical, and catalytic studies.
AB  - The transmetalation of bimetallic copper-sodium silsesquioxane cages, namely,
      [(PhSiO1.5 )10 (CuO)2 (NaO0.5 )2 ] ("Cooling Tower"; 1), [(PhSiO1.5 )12 (CuO)4
      (NaO0.5 )4 ] ("Globule"; 2), and [(PhSiO1.5 )6 (CuO)4 (NaO0.5 )4 (PhSiO1.5 )6 ]
      ("Sandwich"; 3), resulted in the generation of three types of hexanuclear
      cylinder-like copper silsesqui- oxanes, [(PhSiO1.5 )12 (CuO)6 (C4 H9 OH)2 (C2 H5
      OH)6 ] (4), [(PhSiO1.5 )12 (CuO)6 (C4 H8 O2 )4 (PhCN)2 (MeOH)4 ] (5), and
      [(PhSiO1.5 )12 (CuO)6 (NaCl)(C4 H8 O2 )12 (H2 O)2 ] (6). The products show a
      prominent "solvating system-structure" dependency, as determined by X-ray
      diffraction. Topological analysis of cages 1-6 was also performed. In addition,
      DFT theory was used to examine the structures of the Cooling Tower and Cylinder
      compounds, as well as the spin density distributions. Compounds 1, 2, and 5 were
      applied as catalysts for the direct oxidation of alcohols and amines into the
      corresponding amides. Compound 6 is an excellent catalyst in the oxidation
      reactions of benzene and alcohols. 

PMID- 25950427
TI  - A common gustatory and interoceptive representation in the human mid-insula.
AB  - The insula serves as the primary gustatory and viscerosensory region in the
      mammalian cortex. It receives visceral and gustatory afferent projections through
      dedicated brainstem and thalamic nuclei, which suggests a potential role as a
      site for homeostatic integration. For example, while human neuroimaging studies
      of gustation have implicated the dorsal mid-insular cortex as one of the primary
      gustatory regions in the insula, other recent studies have implicated this same
      region of the insula in interoception. This apparent convergence of gustatory and
      interoceptive information could reflect a common neural representation in the
      insula shared by both interoception and gustation. This idea finds support in
      translational studies in rodents, and may constitute a medium for integrating
      homeostatic information with feeding behavior. To assess this possibility,
      healthy volunteers were asked to undergo fMRI while performing tasks involving
      interoceptive attention to visceral sensations as well as a gustatory mapping
      task. Analysis of the unsmoothed, high-resolution fMRI data confirmed shared
      representations of gustatory and visceral interoception within the dorsal mid
      insula. Group conjunction analysis revealed overlapping patterns of activation
      for both tasks in the dorsal mid-insula, and region-of-interest analyses
      confirmed that the dorsal mid-insula regions responsive for visceral
      interoception also exhibit strong responses to tastants.

PMID- 25950428
TI  - Field-evolved resistance to four modes of action of herbicides in a single kochia
      (Kochia scoparia L. Schrad.) population.
AB  - BACKGROUND: Evolution of multiple herbicide resistance in weeds is a serious
      threat to weed management in crop production. Kochia is an economically important
      broadleaf weed in the U.S. Great Plains. This study aimed to confirm resistance
      to four sites of action of herbicides in a single kochia (Kochia scoparia L.
      Schrad.) population from a crop field near Garden City (GC), Kansas, and further
      determine the underlying mechanisms of resistance. RESULTS: One-fourth of the GC
      plants survived the labeled rate or higher of atrazine [photosystem II (PSII)
      inhibitor], and the surviving plants had the Ser-264 to Gly mutation in the psbA
      gene, the target site of atrazine. Results showed that 90% of GC plants survived
      the labeled rate of dicamba, a synthetic auxin. At least 87% of the plants
      survived up to 72 g a.i. ha(-1) of chlorsulfuron [acetolactate synthase (ALS)
      inhibitor], and analysis of the ALS gene revealed the presence of Pro-197 to Thr
      and/or Trp-574 to Lue mutation(s). Most GC plants also survived the labeled rate
      of glyphosate [5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) inhibitor),
      and the resistant plants had 5-9 EPSPS gene copies (relative to the ALS gene).
      CONCLUSION: We confirm the first case of evolution of resistance to four
      herbicide sites of action (PSII, ALS and EPSPS inhibitors and synthetic auxins)
      in a single kochia population, and target-site-based mechanisms confer resistance
      to atrazine, glyphosate and chlorsulfuron.

PMID- 25950429
TI  - Nest suitability, fine-scale population structure and male-mediated dispersal of
      a solitary ground nesting bee in an urban landscape.
AB  - Bees are the primary pollinators of flowering plants in almost all ecosystems.
      Worldwide declines in bee populations have raised awareness about the importance
      of their ecological role in maintaining ecosystem functioning. The naturally
      strong philopatric behavior that some bee species show can be detrimental to
      population viability through increased probability of inbreeding. Furthermore,
      bee populations found in human-altered landscapes, such as urban areas, can
      experience lower levels of gene flow and effective population sizes, increasing
      potential for inbreeding depression in wild bee populations. In this study, we
      investigated the fine-scale population structure of the solitary bee Colletes
      inaequalis in an urbanized landscape. First, we developed a predictive spatial
      model to detect suitable nesting habitat for this ground nesting bee and to
      inform our field search for nests. We genotyped 18 microsatellites in 548 female
      individuals collected from nest aggregations throughout the study area. Genetic
      relatedness estimates revealed that genetic similarity among individuals was
      slightly greater within nest aggregations than among randomly chosen individuals.
      However, genetic structure among nest aggregations was low (Nei's GST = 0.011).
      Reconstruction of parental genotypes revealed greater genetic relatedness among
      females than among males within nest aggregations, suggesting male-mediated
      dispersal as a potentially important mechanism of population connectivity and
      inbreeding avoidance. Size of nesting patch was positively correlated with
      effective population size, but not with other estimators of genetic diversity. We
      detected a positive trend between geographic distance and genetic differentiation
      between nest aggregations. Our landscape genetic models suggest that increased
      urbanization is likely associated with higher levels of inbreeding. Overall,
      these findings emphasize the importance of density and distribution of suitable
      nesting patches for enhancing bee population abundance and connectivity in human
      dominated habitats and highlights the critical contribution of landscape genetic
      studies for enhanced conservation and management of native pollinators. 

PMID- 25950430
TI  - The Effects and Molecular Mechanisms of MiR-106a in Multidrug Resistance Reversal
      in Human Glioma U87/DDP and U251/G Cell Lines.
AB  - Chemotherapy resistance is one of the major obstacles to effective glioma
      therapy. Currently, the mechanism underlying chemotherapy resistance is unclear.
      A recent study showed that miR-106a is an important molecule involved in
      chemotherapy resistance. To explore the effects and mechanisms of miR-106a on
      multidrug resistance reversal in human glioma cells, we silenced miR-106a
      expression in the cisplatin-resistant U87 (U87/DDP) and the gefitinib-resistant
      U251 (U251/G) glioma cell lines and measured the resulting drug sensitivity, cell
      apoptosis rate and rhodamine 123 content. In addition, we detected decreased
      expression of P-glycoprotein, MDR1, MRP1, GST-pi, CDX2, ERCC1, RhoE, Bcl-2,
      Survivin and Topo-II, as well as reduced production of IL-6, IL-8 and TGF-beta in
      these cell lines. Furthermore, we found decreased expression of p-AKT and
      transcriptional activation of NF-kappaB, Twist, AP-1 and Snail in these cell
      lines. These results suggest that miR-106a is a promising therapeutic target for
      the treatment of human multidrug resistant glioma. 

PMID- 25950431
TI  - Chromosomal Behavior during Meiosis in the Progeny of Triticum timopheevii *
      Hexaploid Wild Oat.
AB  - The meiotic behavior of pollen mother cells (PMCs) of the F2 and F3 progeny from
      Triticum timopheevii * hexaploid wild oat was investigated by cytological
      analysis and sequential C-banding-genomic in situ hybridization (GISH) in the
      present study. A cytological analysis showed that the chromosome numbers of the
      F2 and F3 progeny ranged from 28 to 41. A large number of univalents, lagging
      chromosomes, chromosome bridges and micronuclei were found at the metaphase I,
      anaphase I, anaphase II and tetrad stages in the F2 and F3 progeny. The averages
      of univalents were 3.50 and 2.73 per cell, and those of lagging chromosomes were
      3.37 and 1.87 in the F2 and F3 progeny, respectively. The PMC meiotic indices of
      the F2 and F3 progeny were 12.22 and 20.34, respectively, indicating considerable
      genetic instability. A sequential C-banding-GISH analysis revealed that some
      chromosomes and fragments from the hexaploid wild oat were detected at metaphase
      I and anaphase I in the progeny, showing that the progeny were of true
      intergeneric hybrid origin. The alien chromosomes 6A, 7A, 3C and 2D were lost
      during transmission from F2 to F3. In addition, partial T. timopheevii
      chromosomes appeared in the form of univalents or lagging chromosomes, which
      might result from large genome differences between the parents, and the wild oat
      chromosome introgression interfered with the wheat homologues' normally pairing. 

PMID- 25950432
TI  - An Elevated Peripheral Blood Monocyte-to-Lymphocyte Ratio Predicts Poor Prognosis
      in Patients with Primary Pulmonary Lymphoepithelioma-Like Carcinoma.
AB  - Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare type of non
      small cell lung cancer. In this study, we retrospectively reviewed the data from
      74 consecutive patients with pulmonary LELC and investigated the prognostic value
      of pretreatment monocyte-to-lymphocyte ratio (MLR). The cut-off value determined
      by ROC curve for MLR was 0.262. According to this cut-off value, 36 (48.6%)
      patients had lower MLR value (<0.262) at diagnosis. There was no significant
      correlation between MLR level and gender, age, smoking history, stage, and
      lactate dehydrogenase (LDH) level. The 2-year, 5-year, and 10-year OS rate were
      86%, 72%, and 61%, respectively; the 2-year, 5-year, and 10-year PFS rate were
      71%, 63%, and 49%, respectively. In univariate analysis, advanced stage, elevated
      LDH level, and higher MLR value (> = 0.262) were significantly associated with
      poor OS and PFS. In a multivariate Cox regression model that included stage, LDH
      and MLR level, all of these three factors were found to be independent prognostic
      factors for both PFS and OS. In patients who received radical surgery, MLR level
      remained significantly correlated with OS and PFS. In conclusion, we firstly
      demonstrated that pretreatment MLR can be used as a useful independent prognostic
      marker in patients with pulmonary LELC, and might guide us to optimize the
      treatment strategies. However, due to the relatively rarity of this disease and
      the limitation of a retrospective study, further prospective studies performed in
      multicenter are necessary to validate the prognostic value of MLR in pulmonary
      LELC. 

PMID- 25950433
TI  - DNA priming for seasonal influenza vaccine: a phase 1b double-blind randomized
      clinical trial.
AB  - BACKGROUND: The efficacy of current influenza vaccines is limited in vulnerable
      populations. DNA vaccines can be produced rapidly, and may offer a potential
      strategy to improve vaccine immunogenicity, indicated by studies with H5
      influenza DNA vaccine prime followed by inactivated vaccine boost. METHODS: Four
      sites enrolled healthy adults, randomized to receive 2011/12 seasonal influenza
      DNA vaccine prime (n=65) or phosphate buffered saline (PBS) (n=66) administered
      intramuscularly with Biojector. All subjects received the 2012/13 seasonal
      inactivated influenza vaccine, trivalent (IIV3) 36 weeks after the priming
      injection. Vaccine safety and tolerability was the primary objective and
      measurement of antibody response by hemagglutination inhibition (HAI) was the
      secondary objective. RESULTS: The DNA vaccine prime-IIV3 boost regimen was safe
      and well tolerated. Significant differences in HAI responses between the DNA
      vaccine prime and the PBS prime groups were not detected in this study.
      CONCLUSION: While DNA priming significantly improved the response to a
      conventional monovalent H5 vaccine in a previous study, it was not effective in
      adults using seasonal influenza strains, possibly due to pre-existing immunity to
      the prime, unmatched prime and boost antigens, or the lengthy 36 week boost
      interval. Careful optimization of the DNA prime-IIV3 boost regimen as related to
      antigen matching, interval between vaccinations, and pre-existing immune
      responses to influenza is likely to be needed in further evaluations of this
      vaccine strategy. In particular, testing this concept in younger age groups with
      less prior exposure to seasonal influenza strains may be informative. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01498718.

PMID- 25950434
TI  - Impact of the quality of bowel cleansing on the efficacy of colonic cancer
      screening: a prospective, randomized, blinded study.
AB  - OBJECTIVES: Efficacy of two low volume bowel cleansing preparations, polyethylene
      glycol plus ascorbate (PEG + Asc) and sodium picosulfate/magnesium citrate
      (NaPic/MgCit), were compared for polyp and adenoma detection rate (PDR and ADR)
      and overall cleansing ability. Primary endpoint was PDR (the number of patients
      with >= 1 polypoid or flat lesion recorded by the colonoscopist). METHODS:
      Diagnostic, surveillance or screening colonoscopy patients were enrolled into
      this investigator-blinded, multi-center Phase IV study and randomized 1:1 to
      receive PEG + Asc (administered the evening before and the morning of
      colonoscopy, per label) or NaPic/MgCit (administered in the morning and afternoon
      the day before colonoscopy, per label). The blinded colonoscopist documented any
      lesion and assessed cleansing quality (Harefield Cleansing Scale). RESULTS: Of
      394 patients who completed the study, 393 (PEG + Asc, N = 200; NaPic/MgCit, N =
      193) had a colonoscopy. Overall PDR for PEG+Asc versus NaPic/MgCit was 51.5%
      versus 44.0%, p = 0.139. PDR and ADR on the right side of the bowel were
      significantly higher with PEG + Asc versus NaPic/MgCit (PDR: 56[28.0%] versus
      32[16.6%], p = 0.007; ADR: 42[21.0%] versus 23[11.9%], p = 0.015), as was
      detection of flat lesions (43[21.5%] versus 25[13.0%], p = 0.025). Cleansing
      quality was better with PEG + Asc than NaPic/MgCit (98.5% versus 57.5% considered
      successful cleansing). Overall, there were 132 treatment-emergent adverse events
      (93 versus 39 for PEG+Asc and NaPic/MgCit, respectively). These were mainly mild
      abdominal symptoms, all of which were reported for higher proportions of patients
      in the PEG+Asc than NaPic/MgCit group. Twice as many patients in the NaPic/MgCit
      versus the PEG + Asc group reported tolerance of cleansing solution as 'very
      good'. CONCLUSIONS: Compared with NaPic/MgCit, PEG + Asc may be more efficacious
      for overall cleansing ability, and subsequent detection of right-sided and flat
      lesions. This is likely attributable to the different administration schedules of
      the two bowel cleansing preparations, which may positively impact the detection
      and prevention of colorectal cancer, thereby improving mortality rates. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01689792.

PMID- 25950435
TI  - Cervical cancer screening: what is cost-effectiveness?

PMID- 25950436
TI  - Advanced Technologies in Cervical Cancer Screening ASCCP Biennial Meeting 1998.

PMID- 25950437
TI  - piRNAs from Pig Testis Provide Evidence for a Conserved Role of the Piwi Pathway
      in Post-Transcriptional Gene Regulation in Mammals.
AB  - Piwi-interacting (pi-) RNAs guide germline-expressed Piwi proteins in order to
      suppress the activity of transposable elements (TEs). But notably, the majority
      of pachytene piRNAs in mammalian testes is not related to TEs. This raises the
      question of whether the Piwi/piRNA pathway exerts functions beyond TE silencing.
      Although gene-derived piRNAs were described many times, a possible gene
      regulatory function was doubted due to the absence of antisense piRNAs. Here we
      sequenced and analyzed piRNAs expressed in the adult testis of the pig, as this
      taxon possesses the full set of mammalian Piwi paralogs while their spermatozoa
      are marked by an extreme fitness due to selective breeding. We provide an
      exhaustive characterization of porcine piRNAs and genomic piRNA clusters.
      Moreover, we reveal that both sense and antisense piRNAs derive from protein
      coding genes, while exhibiting features that clearly show that they originate
      from the Piwi/piRNA-mediated post-transcriptional silencing pathway, commonly
      referred to as ping-pong cycle. We further show that the majority of identified
      piRNA clusters in the porcine genome spans exonic sequences of protein-coding
      genes or pseudogenes, which reveals a mechanism by which primary antisense piRNAs
      directed against mRNA can be generated. Our data provide evidence that spliced
      mRNAs, derived from such loci, are not only targeted by piRNAs but are also
      subject to ping-pong cycle processing. Finally, we demonstrate that homologous
      genes are targeted and processed by piRNAs in pig, mouse and human. Altogether,
      this strongly suggests a conserved role for the mammalian Piwi/piRNA pathway in
      post-transcriptional regulation of protein-coding genes, which did not receive
      much attention so far. 

PMID- 25950439
TI  - Accounting for genetic architecture improves sequence based genomic prediction
      for a Drosophila fitness trait.
AB  - The ability to predict quantitative trait phenotypes from molecular polymorphism
      data will revolutionize evolutionary biology, medicine and human biology, and
      animal and plant breeding. Efforts to map quantitative trait loci have yielded
      novel insights into the biology of quantitative traits, but the combination of
      individually significant quantitative trait loci typically has low predictive
      ability. Utilizing all segregating variants can give good predictive ability in
      plant and animal breeding populations, but gives little insight into trait
      biology. Here, we used the Drosophila Genetic Reference Panel to perform both a
      genome wide association analysis and genomic prediction for the fitness-related
      trait chill coma recovery time. We found substantial total genetic variation for
      chill coma recovery time, with a genetic architecture that differs between males
      and females, a small number of molecular variants with large main effects, and
      evidence for epistasis. Although the top additive variants explained 36% (17%) of
      the genetic variance among lines in females (males), the predictive ability using
      genomic best linear unbiased prediction and a relationship matrix using all
      common segregating variants was very low for females and zero for males. We
      hypothesized that the low predictive ability was due to the mismatch between the
      infinitesimal genetic architecture assumed by the genomic best linear unbiased
      prediction model and the true genetic architecture of chill coma recovery time.
      Indeed, we found that the predictive ability of the genomic best linear unbiased
      prediction model is markedly improved when we combine quantitative trait locus
      mapping with genomic prediction by only including the top variants associated
      with main and epistatic effects in the relationship matrix. This trait-associated
      prediction approach has the advantage that it yields biologically interpretable
      prediction models. 

PMID- 25950438
TI  - Parallel Gene Expression Differences between Low and High Latitude Populations of
      Drosophila melanogaster and D. simulans.
AB  - Gene expression variation within species is relatively common, however, the role
      of natural selection in the maintenance of this variation is poorly understood.
      Here we investigate low and high latitude populations of Drosophila melanogaster
      and its sister species, D. simulans, to determine whether the two species show
      similar patterns of population differentiation, consistent with a role for
      spatially varying selection in maintaining gene expression variation. We compared
      at two temperatures the whole male transcriptome of D. melanogaster and D.
      simulans sampled from Panama City (Panama) and Maine (USA). We observed a
      significant excess of genes exhibiting differential expression in both species,
      consistent with parallel adaptation to heterogeneous environments. Moreover, the
      majority of genes showing parallel expression differentiation showed the same
      direction of differential expression in the two species and the magnitudes of
      expression differences between high and low latitude populations were correlated
      across species, further bolstering the conclusion that parallelism for expression
      phenotypes results from spatially varying selection. However, the species also
      exhibited important differences in expression phenotypes. For example, the
      genomic extent of genotype * environment interaction was much more common in D.
      melanogaster. Highly differentiated SNPs between low and high latitudes were
      enriched in the 3' UTRs and CDS of the geographically differently expressed genes
      in both species, consistent with an important role for cis-acting variants in
      driving local adaptation for expression-related phenotypes. 

PMID- 25950440
TI  - BOLD fMRI of C-Fiber Mediated Nociceptive Processing in Mouse Brain in Response
      to Thermal Stimulation of the Forepaws.
AB  - Functional magnetic resonance imaging (fMRI) in rodents enables non-invasive
      studies of brain function in response to peripheral input or at rest. In this
      study we describe a thermal stimulation paradigm using infrared laser diodes to
      apply noxious heat to the forepaw of mice in order to study nociceptive
      processing. Stimulation at 45 and 46 degrees C led to robust BOLD signal changes
      in various brain structures including the somatosensory cortices and the
      thalamus. The BOLD signal amplitude scaled with the temperature applied but not
      with the area irradiated by the laser beam. To demonstrate the specificity of the
      paradigm for assessing nociceptive signaling we administered the quaternary
      lidocaine derivative QX-314 to the forepaws, which due to its positive charge
      cannot readily cross biological membranes. However, upon activation of TRPV1
      channels following the administration of capsaicin the BOLD signal was largely
      abolished, indicative of a selective block of the C-fiber nociceptors due to QX
      314 having entered the cells via the now open TRPV1 channels. This demonstrates
      that the cerebral BOLD response to thermal noxious paw stimulation is
      specifically mediated by C-fibers. 

PMID- 25950441
TI  - Detection of K-ras Mutations in Predicting Efficacy of Epidermal Growth Factor
      Receptor Tyrosine Kinase (EGFR-TK) Inhibitor in Patients with Metastatic
      Colorectal Cancer.
AB  - Epidermal growth factor receptor tyrosine kinase (EGFR-TK) inhibitors are useful
      in treating different advanced human cancers; however, their clinical efficacy
      varies. This study detected K-ras mutations to predict the efficacy of EGFR-TK
      inhibitor cetuximab treatment on Chinese patients with metastatic colorectal
      cancer (mCRC). A total of 87 patients with metastatic colorectal cancer were
      treated with cetuximab for 2-16 months, in combination with chemotherapy between
      August 2008 and July 2012, and tissue samples were used to detect K-ras
      mutations. The data showed that K-ras mutation occurred in 27/87 (31%). The
      objective response rates and disease control rate in K-ras wild type and mutant
      patients were 42% (25/60) versus 11% (3/27) (p<0.05) and 60% (36/60) versus 26%
      (7/27) (p<0.05), respectively. Patients with the wild-type K-ras had
      significantly higher median survival times and progression-free survival, than
      patients with mutated K-ras (21 months versus 17 months, p=0.017; 10 months
      versus 6 months, p=0.6). These findings suggest that a high frequency of K-ras
      mutations occurs in Chinese mCRC patients and that K-ras mutation is required to
      select patients for eligibility for cetuximab therapy. Further prospective
      studies using a large sample size are needed to confirm these preliminary
      findings. 

PMID- 25950442
TI  - Risk prediction for patients with hepatocellular carcinoma undergoing
      chemoembolization: development of a prediction model.
AB  - BACKGROUNDS & AIMS: We aimed to generate and validate a novel risk prediction
      model for patients with hepatocellular carcinoma (HCC) undergoing transarterial
      chemoembolization (TACE). METHODS: Patients receiving TACE as the first-line
      therapy between 2006 and 2009 were selected from the databases of two major
      tertiary hospitals in Korea. This study population was randomly assigned into
      training (n = 340) and validation (n = 145) sets. From a multivariate Cox
      regression model for overall survival (OS), tumour Size, tumour Number, baseline
      Alpha-foetoprotein level, Child-Pugh class and Objective radiological Response
      after the first TACE session were selected and then scored to generate a 10-point
      risk prediction model (named as "SNACOR" model) in the training set. Thereafter,
      the prognostic performance was assessed in the validation set. RESULTS: In the
      training set, the time-dependent areas under receiver-operating characteristic
      curves (AUROCs) for OS at 1-, 3- and 6-years were 0.756, 0.754 and 0.742
      respectively. According to the score of the SNACOR model, patients were
      stratified into three groups; low- (score 0-2), intermediate- (score 3-6) and
      high-risk group (score 7-10) respectively. The low-risk group had the longest
      median OS (49.8 months), followed by intermediate- (30.7 months) and high-risk
      group (12.4 months) (log-rank test, P < 0.001). Compared with the low-risk group,
      the intermediate-risk (hazard ratio [HR] 2.13, P < 0.001) and high-risk group (HR
      6.17, P < 0.001) retained significant risks of death. Similar results were
      obtained in the validation set. CONCLUSION: A simple-to-use SNACOR model for
      patients with HCC treated with TACE might be helpful in appropriate
      prognostification and guidance for decision of further treatment strategies.

PMID- 25950446
TI  - Tackling community integration in mental health home visit integration in
      Finland.
AB  - Integration - and its synonym inclusion - is emphasised in the western welfare
      states and in the European Union in particular. Integration is also a central
      topic in the social sciences and in current mental health and homelessness
      research and practice. As mental healthcare has shifted from psychiatric
      hospitals to the community, it has inevitably become involved with housing and
      integration issues. This article explores how community integration is understood
      and tackled in mental health floating support services (FSSs) and, more
      precisely, in service user-practitioner home visit interaction. The aim, through
      shedding light on how the idea of integration is present and discussed in front
      line mental health practices, is to offer a 'template' on how we might, in a
      systematic and reflective way, develop community integration research and
      practice. The analysis is based on ethnomethodological and micro-sociological
      interaction research. The research settings are two FSSs located in a large
      Finnish city. The data contain 24 audio-recorded and transcribed home visits
      conducted in 2011 and 2012 with 16 different service users. The study shows how
      the participants in service user-practitioner interaction give meaning to
      community integration and make decisions about how it should (or should not) be
      enhanced in each individual case. This activity is called community integration
      work in action. Community integration work in action is based on various
      dimensions of integration: getting out of the house, participating in group
      activities and getting along with those involved in one's life and working life.
      Additionally, the analysis demonstrates how community integration work is
      accomplished by discursive devices (resistance, positioning, excuses and
      justifications, delicacy and advice-giving). The article concludes that community
      integration is about interaction: it is not only service users' individual
      challenge but also a social challenge, our challenge.

PMID- 25950443
TI  - Methodological variation in economic evaluations conducted in low- and middle
      income countries: information for reference case development.
AB  - Information generated from economic evaluation is increasingly being used to
      inform health resource allocation decisions globally, including in low- and
      middle- income countries. However, a crucial consideration for users of the
      information at a policy level, e.g. funding agencies, is whether the studies are
      comparable, provide sufficient detail to inform policy decision making, and
      incorporate inputs from data sources that are reliable and relevant to the
      context. This review was conducted to inform a methodological standardisation
      workstream at the Bill and Melinda Gates Foundation (BMGF) and assesses BMGF
      funded cost-per-DALY economic evaluations in four programme areas (malaria,
      tuberculosis, HIV/AIDS and vaccines) in terms of variation in methodology, use of
      evidence, and quality of reporting. The findings suggest that there is room for
      improvement in the three areas of assessment, and support the case for the
      introduction of a standardised methodology or reference case by the BMGF. The
      findings are also instructive for all institutions that fund economic evaluations
      in LMICs and who have a desire to improve the ability of economic evaluations to
      inform resource allocation decisions. 

PMID- 25950447
TI  - A recurrent melanocytic nevus phenomenon in the setting of Hailey-Hailey disease.
AB  - Atypical acquired melanocytic nevi in patients with epidermolysis bullosa (EB)
      have been referred to as EB nevi and are considered to be a type of recurrent
      nevus with atypical but distinctive histopathologic findings. Herein, we describe
      an atypical nevus in a patient with Hailey-Hailey disease with different
      histopathologic findings from EB nevi because of presumably different
      pathogenesis. It is important to be aware that the recurrent nevi phenomenon can
      be seen in acantholytic conditions as well as blistering disorders, given these
      lesions may clinically resemble melanoma. 

PMID- 25950448
TI  - Mass Media and HIV/AIDS Prevention Among Female Sex Workers in Beijing, China.
AB  - The current study aimed to identify the sources of HIV prevention information for
      female sex workers in Beijing and assess the associations between levels of mass
      media exposure of HIV/AIDS prevention information and HIV/AIDS knowledge as well
      as condom use-related attitudes, beliefs, and behaviors. Cross-sectional data
      were collected from 359 female sex workers in Beijing, China. Chi-square tests
      and one-way ANOVA tests were employed. Female sex workers sampled in Beijing were
      more likely to obtain HIV/AIDS prevention information from television and street
      posters than radio and the Internet. However, a higher level of exposure to and a
      lasting impression on online information were significantly associated with a
      higher level of condom use self-efficacy and more consistent condom use among the
      participants. Exposure to HIV/AIDS prevention information delivered by radio,
      street posters, and the Internet was found to be associated with sexual
      communication about HIV or condom use with sexual partners. Overall, this study
      provides preliminary evidence of the utility of various mass media outlets in
      delivering HIV/AIDS prevention information among female sex workers in China.
      Future studies are needed to systematically examine the effectiveness of mass
      media-based prevention education on HIV/AIDS related attitudes and behaviors
      among female sex workers and other populations in China. 

PMID- 25950449
TI  - Severity and duration of pain after colonoscopy and gastroscopy: a cohort study.
AB  - AIMS AND OBJECTIVES: This study aimed to determine the prevalence, severity,
      location and duration of pain post-colonoscopy, and to explore possible
      associations between pain, demographic variables and diagnostic findings. The
      study also sought to provide information to guide decision-making on CO2
      insufflation. BACKGROUND: Colonoscopy with sedation is a common day surgery
      procedure in Australia. Attendance for colonoscopy is influenced by patient
      expectations, particularly about pain. Research on post-colonoscopy pain has
      focussed on pain experienced immediately post-procedure, with few studies
      investigating pain beyond 24 hours. DESIGN: Follow-up study using patient
      completed Pain Numerical Rating Scales. METHODS: Patients undergoing colonoscopy
      at a single hospital day surgery unit were invited to complete Pain Numerical
      Rating Scales (where 0 = no pain and 10 = worst possible pain) three times daily
      for three days post-colonoscopy. RESULTS: Among the 277 participants, 124 (45%)
      reported pain at any time during follow-up. Twenty-one (8%) participants
      experienced pain on each of the three days. Pain was most commonly experienced in
      the hypogastric and iliac regions. The severity of pain was low, with only 33
      participants self-administering analgesics (paracetamol or nonsteroidal anti
      inflammatory drugs) during follow-up. Participants who had both colonoscopy and
      gastroscopy were not more likely to report pain overall. However, they were more
      likely to report pain on days 2 and 3 and were also more likely to take
      analgesics. Pain was not associated with procedure duration, abdominal
      pressurisation, removal of polyps, diverticulitis, inflammatory bowel disease or
      the presence of benign or malignant lesions. CONCLUSIONS: This research indicates
      that fewer than half of the patients undergoing colonoscopy will experience post
      procedure pain and that just over one in ten patients will require analgesics.
      Patients undergoing both gastroscopy and colonoscopy are more likely to
      experience pain for longer and require over-the-counter analgesics. The low
      prevalence of pain suggests that room air insufflation is an acceptable
      alternative to more expensive CO2 . RELEVANCE TO CLINICAL PRACTICE: The findings
      provide evidence for nurses and clinicians to advise patients about the
      likelihood of experiencing pain post-colonoscopy, and the characteristics of this
      pain. Nurses may reassure patients that pain is not more likely among patients
      diagnosed with colorectal disease or malignancy. Patients who have persistent
      pain for longer than 24 hours post-colonoscopy should be advised to seek medical
      care to investigate the cause of their pain.

PMID- 25950450
TI  - Mitogen-activated protein kinase phosphatase-1 prevents lipopolysaccharide
      induced apoptosis in immature rat intestinal epithelial cells.
AB  - BACKGROUND: Necrotizing enterocolitis is characterized by intestinal inflammation
      and epithelial barrier dysfunction. Mitogen-activated protein kinase (MAPK)
      phosphatase (MKP)-1 plays a pivotal role in the feedback control of MAPK
      signaling, which regulates inflammation and apoptosis. We hypothesized that MKP-1
      prevents lipopolysaccharide (LPS)-induced apoptosis in intestinal epithelial
      cells. METHODS: Western blot analysis and qPCR were used to assess MKP-1, MAPK
      (p38, extracellular signal-regulated kinase (ERK), and c-Jun N terminal kinases
      (JNK)), caspase 3, caspase 9, tumor necrosis factor (TNF)-alpha, and
      cyclooxygenase (COX)-2 expression levels in rIEC-6 enterocytes. MKP-1 expression
      was inhibited using small interfering RNA (siRNA) methodology. Viable cell number
      was determined using trypan blue exclusion. RESULTS: LPS stimulation led to
      activation of p38, JNK, and ERK, and induction of MKP-1 mRNA and protein
      expression. The induction of MKP-1 was associated with a decrease in p38
      phosphorylation, and knockdown of MKP-1 prolonged p38 phosphorylation. While LPS
      stimulation significantly attenuated proliferation of rIEC-6 cells transfected
      with scramble siRNA, LPS stimulation resulted in a net decrease in viable cell
      number in cells transfected with MKP-1 siRNA. Following LPS stimulation, MKP-1
      knockdown resulted in greater caspase 3 and 9 activities and greater
      proinflammatory cytokine (TNF-alpha, COX-2) expression than in cells transfected
      with scramble siRNA. CONCLUSION: Our results demonstrate that MKP-1 has a central
      role in preventing inflammation-induced apoptosis in rIEC-6 enterocytes.

PMID- 25950451
TI  - Increased airway reactivity in a neonatal mouse model of continuous positive
      airway pressure.
AB  - BACKGROUND: Continuous positive airway pressure (CPAP) is a primary form of
      respiratory support used in the intensive care of preterm infants, but its long
      term effects on airway (AW) function are unknown. METHODS: We developed a
      neonatal mouse model of CPAP treatment to determine whether it modifies later AW
      reactivity. Unanesthetized spontaneously breathing mice were fitted with a mask
      to deliver CPAP (6 cmH2O, 3 h/day) for 7 consecutive days starting at postnatal
      day 1. AW reactivity to methacholine was assessed using the in vitro living lung
      slice preparation. RESULTS: One week of CPAP increased AW responsiveness to
      methacholine in male, but not female mice, compared to untreated control animals.
      The AW hyper-reactivity of male mice persisted for 2 wk (at P21) after CPAP
      treatment ended. Four days of CPAP, however, did not significantly increase AW
      reactivity. Females also exhibited AW hyper-reactivity at P21, suggesting a
      delayed response to early (7 d) CPAP treatment. The effects of 7 d of CPAP on
      hyper-reactivity to methacholine were unique to smaller AWs whereas larger ones
      were relatively unaffected. CONCLUSION: These data may be important to our
      understanding of the potential long-term consequences of neonatal CPAP therapy
      used in the intensive care of preterm infants.

PMID- 25950452
TI  - Association of prematurity with the development of infantile hypertrophic pyloric
      stenosis.
AB  - BACKGROUND: Infantile hypertrophic pyloric stenosis (IHPS) has several known risk
      factors. The association between prematurity and IHPS and the timeline of
      presentation are poorly defined. Our aim was to evaluate the associations between
      IHPS and prematurity. METHODS: We performed a retrospective cohort study of
      1,074,236 children born between June 2001 and April 2012 in the US Military
      Health System. IHPS cases and gestational ages (GA) were identified using billing
      codes. Additional risk factors for IHPS were controlled for in a multivariable
      logistic regression model. RESULTS: The incidence of IHPS was 2.99 per 1,000 in
      preterm infants and 2.25 per 1,000 in full term (relative risk (RR) = 1.33, 95%
      confidence interval (CI) 1.16-1.54). The adjusted odds ratio for prematurity was
      1.26 (95% CI 1.08-1.46). The median (interquartile range (IQR)) chronological age
      at presentation was 40 d (30-56) in preterm infants vs. 33 d (26-45) in full term
      (P < 0.001). Median postmenstrual age at presentation was 42 wk in preterm
      infants (40-42) vs. 45 wk (44-46) in full term (P < 0.001). CONCLUSION:
      Prematurity is associated with IHPS. Premature infants develop IHPS at a later
      chronological age, but earlier postmenstrual age, than term infants. Providers
      should have an increased concern for IHPS development in premature infants.

PMID- 25950453
TI  - Efficacy and safety of acupuncture in children: an overview of systematic
      reviews.
AB  - In recent years, acupuncture has increasingly being integrated into pediatric
      health care. It was used on ~150,000 children (0.2%). We aim to update the
      evidence for the efficacy and safety of acupuncture for children and evaluate the
      methodological qualities of these studies to improve future research in this
      area. We included 24 systematic reviews, comprising 142 randomized controlled
      trials (RCTs) with 12,787 participants. Only 25% (6/24) reviews were considered
      to be high quality (10.00 +/- 0.63). High-quality systematic reviews and Cochrane
      systematic reviews tend to yield neutral or negative results (P = 0.052, 0.009
      respectively). The efficacy of acupuncture for five diseases (Cerebral Palsy
      (CP), nocturnal enuresis, tic disorders, amblyopia, and pain reduction) is
      promising. It was unclear for hypoxic ischemic encephalopathy, attention deficit
      hyperactivity disorder, mumps, autism spectrum disorder (ASD), asthma,
      nausea/vomiting, and myopia. Acupuncture is not effective for epilepsy. Only six
      reviews reported adverse events (AEs) and no fatal side effects were reported.
      The efficacy of acupuncture for some diseases is promising and there have been no
      fatal side effects reported. Further high-quality studies are justified, with
      five diseases in particular as research priorities.

PMID- 25950455
TI  - Neonatal jaundice and risks of childhood allergic diseases: a population-based
      cohort study.
AB  - BACKGROUND: Only a few studies have systemically analyzed the association between
      neonatal jaundice and childhood-onset allergic diseases. METHODS: From 2000 to
      2007, 27,693 neonates with newly diagnosed neonatal jaundice and 55,367 matched
      nonneonatal jaundice cohorts were identified. The incidences and hazard ratios
      (HRs) of five allergic diseases, namely allergic conjunctivitis (AC), allergic
      rhinitis (AR), atopic dermatitis (AD), asthma, and urticaria, by the end of 2008
      were calculated. RESULTS: The incidence density and HRs of the five allergic
      diseases were greater in the neonatal jaundice cohort than in the nonneonatal
      jaundice cohort, and the HRs declined modestly with age. The HRs for AR (HR =
      2.51, 95% confidence interval (CI) = 2.43-2.59) and AD (HR = 2.51, 95% CI = 2.40
      2.62) were the highest, and that for urticaria was the lowest (HR = 2.06, 95% CI
      = 1.94-2.19). The HRs of allergic diseases were substantially greater for boys
      and those requiring phototherapy. The HRs of the allergic diseases, except
      urticaria (HR = 2.49, 95% CI = 1.57-3.97), were not significantly different
      between the neonatal jaundice regardless of whether the patients received
      exchange transfusion. CONCLUSION: Neonatal jaundice is associated with the
      development of allergic diseases in early childhood.

PMID- 25950456
TI  - Curcumin prevents perfluorooctane sulfonate-induced genotoxicity and oxidative
      DNA damage in rat peripheral blood.
AB  - Perfluorooctane sulfonate (PFOS) is a man-made fluorosurfactant and global
      pollutant. PFOS a persistent and bioaccumulative compound, and it is widely
      distributed in humans and wildlife. Therefore, it was added to Annex B of the
      Stockholm Convention on Persistent Organic Pollutants in May 2009. Curcumin is a
      natural polyphenolic compound abundant in the rhizome of the perennial herb
      turmeric. It is commonly used as a dietary spice and coloring agent in cooking
      and anecdotally as an herb in traditional Asian medicine. In this study, male
      rats were treated with three different PFOS doses (0.6, 1.25, and 2.5 mg/kg) and
      one dose of curcumin, from Curcuma longa (80 mg/kg), and combined three doses of
      PFOS with 80 mg/kg dose of curcumin by gavage for 30 d at 48 h intervals. Here,
      we investigated the DNA damage via single-cell gel electrophoresis/comet assay
      and micronucleus test in rat peripheral blood in vivo. It is found that all doses
      of PFOS increased micronucleus frequency (p < 0.05) and strongly induced DNA
      damage in peripheral blood in two different parameters; the damaged cell percent
      and genetically damage index, and curcumin prevented the formation of DNA damage
      induced by PFOS. Results showed that curcumin inhibited DNA damage including GDI
      at certain levels at statistical manner, 30.07%, 54.41%, and 36.99% for 0.6
      mg/kg, 1.25 mg/kg, and 2.5 mg/kg.

PMID- 25950454
TI  - Hypoxic-ischemic brain damage induces distant inflammatory lung injury in newborn
      piglets.
AB  - BACKGROUND: We aimed to investigate whether neonatal hypoxic-ischemic (HI) brain
      injury induces inflammatory lung damage. METHODS: Thus, hypoxic (HYP, FiO2 10%
      for 30 min), ischemic (ISC, bilateral carotid flow interruption for 30 min), or
      HI event was performed in 1-2-d-old piglets. Dynamic compliance (Cdyn),
      oxygenation index (OI), and extravascular lung water (EVLW) were monitored for 6
      h. Then, histologic damage was assessed in brain and lung (lung injury severity
      score). Total protein content (TPC) was determined in broncoalveolar lavage fluid
      (BALF), and IL-1beta concentration was measured in lung and brain tissues and
      blood. RESULTS: Piglets without hypoxia or ischemia served as controls (SHM). HI
      induced brain damage was associated with decreased Cdyn, increased OI and EVLW,
      and histologic lung damage (interstitial leukocyte infiltration, congestive
      hyperemia, and interstitial edema). BALF TPC was increased, suggesting
      inflammatory damage. In agreement, tissue IL-1beta concentration increased in the
      brain and lung, in correspondence with increased IL-1beta serum concentration.
      Neither HYP nor ISC alone led to brain or lung damage. CONCLUSION: HI brain
      damage in newborn piglets led to inflammatory lung damage, suggesting an
      additional mechanism accounting for the development of lung dysfunction after
      neonatal HI encephalopathy.

PMID- 25950457
TI  - Do I Mirror Your Mood if We're Peas in a Pod? Similarity and Liking in the Social
      Induction of Affect.
AB  - The present study investigates whether similarity in personality traits between a
      sender displaying affect and a receiver observing it influences the social
      induction of affect. We hypothesized that exposure to a similar sender would
      foster concordant affective reactions, whereas exposure to a dissimilar sender
      would foster discordant ones. To induce affect, we used short videos presenting a
      sender displaying happy versus sad emotional expressions. To manipulate
      personality similarity, we used a software program to generate brief bogus
      descriptions of the sender based on the receivers' prior responses to personality
      items. Our results demonstrated that dissimilarity led to decreased liking and,
      as a result, reduced the tendency to react with concordant affect to a happy
      sender's emotional expression. However, we found no evidence supporting the
      induction of discordant affective reactions.

PMID- 25950459
TI  - A seed mixture increases dominance of resistance to Bt cotton in Helicoverpa zea.
AB  - Widely grown transgenic crops producing insecticidal proteins from Bacillus
      thuringiensis (Bt) can benefit agriculture, but adaptation by pests threatens
      their continued success. Refuges of host plants that do not make Bt toxins can
      promote survival of susceptible insects and delay evolution of resistance,
      particularly if resistance is inherited as a recessive trait. However, data have
      been lacking to compare the dominance of resistance when Bt and non-Bt seeds are
      planted in random mixtures versus separate blocks. Here we report results from
      greenhouse experiments with transgenic cotton producing Bt toxin Cry1Ac and the
      bollworm, Helicoverpa zea, showing that the dominance of resistance was
      significantly higher in a seed mixture relative to a block of Bt cotton. The
      proportion of larvae on non-Bt cotton plants in the seed mixture was also
      significantly higher than expected under the null hypothesis of random
      distribution. In simulations based on observed survival, resistance evolved 2- to
      4.5-fold faster in the seed mixture relative to separate blocks of Bt and non-Bt
      cotton. These findings support previous modelling results indicating that block
      refuges may be more effective than seed mixtures for delaying resistance in pests
      with mobile larvae and inherently low susceptibility to the toxins in Bt crops. 

PMID- 25950458
TI  - Circadian variations of clock gene Per2 and cell cycle genes in different stages
      of carcinogenesis in golden hamster buccal mucosa.
AB  - Previous studies have suggested that the expression of clock genes have circadian
      rhythms, and many cell cycle genes are regulated by clock genes. The disruption
      of circadian rhythms appears to be associated with the acceleration of cancer
      development. To investigate the circadian patterns of the clock gene Per2 and of
      cell cycle genes p53, Cyclin D1, CDK1 and Cyclin B1 in different stages of
      carcinogenesis, the daily mRNA profiles of these genes were detected by real-time
      RT-PCR in dimethylbenzanthracene-induced cancer, in precancerous lesions and in
      normal tissues. Per2, p53, Cyclin D1 and CDK1 showed circadian rhythms in the 3
      different stages of carcinogenesis, whereas the circadian rhythm of Cyclin B1 was
      absent in the precancerous lesions. The mesors and amplitudes of Per2 and p53
      were decreased (P < 0.05), but the mesors of Cyclin D1, CDK1 and Cyclin B1 were
      increased with the development of cancer (P < 0.05). Compared with the normal
      tissues, the acrophases of Per2 and CDK1 were earlier in precancerous lesions,
      and the acrophases of Cyclin D1, CDK1 and Cyclin B1 occurred later in the cancer
      cells. Our study represents the first demonstration of the circadian pattern
      variations of these genes in different stages of carcinogenesis. 

PMID- 25950460
TI  - Pediatric obsessive-compulsive disorder: an update for advanced practice
      psychiatric nurses.
AB  - Obsessive-compulsive disorder (OCD) may have an onset in childhood or adolescence
      resulting in significant functional impairment and disability into adulthood.
      There are frequently developmental differences in the content of the obsessions
      and compulsions in youth compared to adults. Lack of insight or shame may result
      in failure of the youth to seek treatment. This delay in treatment may lead to
      the development of other psychiatric comorbidities, including suicide. Evidence
      based treatments for OCD include cognitive behavioral therapy and
      exposure/response prevention, and in moderate to severe cases, use of selective
      serotonin reuptake inhibitors is indicated. Advanced practice psychiatric nurses
      are in a unique position to provide psychoeducation, psychotherapy, and
      medications, if indicated, to youth with this condition to improve functioning
      and reduce morbidity and mortality. This article will provide an overview of the
      diagnostic criteria for OCD, etiologies, assessment strategies, differential
      diagnoses, common comorbidities, and evidence-based treatment options. 

PMID- 25950462
TI  - Identification and assessment of functional performance in mild cognitive
      impairment: a survey of occupational therapy practices.
AB  - BACKGROUND/AIM: Despite the amount of research evidence pointing to functional
      changes experienced by individuals with mild cognitive impairment (MCI), we still
      do not understand how occupational therapists are currently addressing these
      concerns. Thus, we designed a national study to investigate Canadian occupational
      therapists practices with this clientele. METHODS: We conducted a Canada-wide
      online survey to investigate occupational therapists' practices with clients with
      potential MCI. Clinicians were prompted by a case vignette that described two
      clients: one vignette included cues associated with amnestic MCI (aMCI), the
      other non-amnestic MCI (naMCI). Specifically, clinicians were asked to identify
      potential concerns and to indicate the screening and assessment tools they would
      use in clinical practice. RESULTS: Two hundred and eighty-five participants met
      the inclusion criteria and were included in the final analysis. The average
      clinician age was 38.6 (SD = 10.3), 92% were female and 71.2% worked full-time.
      Almost all clinicians identified a concern in both vignettes, with cognitive
      concerns being identified more frequently than functional concerns [i.e.
      Instrumental Activities of Daily Living (IADL) concerns]. In terms of assessment
      practices, 18 standardised IADL assessments and 10 standardised cognitive
      assessments have been reported. CONCLUSION: Encouragingly, almost all clinicians
      identified a concern. However, some are still missing the IADL cues. Moreover,
      the lack of consensus in terms of which assessment practices to employ indicates
      that clinicians might benefit from guidelines in this area of practice.

PMID- 25950461
TI  - Restoring the ON Switch in Blind Retinas: Opto-mGluR6, a Next-Generation, Cell
      Tailored Optogenetic Tool.
AB  - Photoreceptor degeneration is one of the most prevalent causes of blindness.
      Despite photoreceptor loss, the inner retina and central visual pathways remain
      intact over an extended time period, which has led to creative optogenetic
      approaches to restore light sensitivity in the surviving inner retina. The major
      drawbacks of all optogenetic tools recently developed and tested in mouse models
      are their low light sensitivity and lack of physiological compatibility. Here we
      introduce a next-generation optogenetic tool, Opto-mGluR6, designed for retinal
      ON-bipolar cells, which overcomes these limitations. We show that Opto-mGluR6, a
      chimeric protein consisting of the intracellular domains of the ON-bipolar cell
      specific metabotropic glutamate receptor mGluR6 and the light-sensing domains of
      melanopsin, reliably recovers vision at the retinal, cortical, and behavioral
      levels under moderate daylight illumination. 

PMID- 25950463
TI  - Using circulating tumor cells to guide therapy in breast cancer: could this
      replace biopsies?

PMID- 25950464
TI  - Interplay of structure, magnetism, and superconductivity in Se substituted iron
      telluride with excess Fe.
AB  - We investigated the evolution of the temperature-composition phase diagram of
      Fe(1+y)Te upon Se substitution. In particular, the effect of Se substitution on
      the two-step, coupled magneto-structural transition in Fe(1+y)Te single crystals
      is investigated. To this end, the nominal Fe excess was kept at y = 0.12. For low
      Se concentrations, the two magneto-structural transitions displayed a tendency to
      merge. In spite of the high Fe-content, superconductivity emerges for Se
      concentrations x ? 0.1. We present a temperature-composition phase diagram to
      demonstrate the interplay of structure, magnetism and superconductivity in these
      ternary Fe-chalcogenides.

PMID- 25950465
TI  - Atypical neuroretinitis in secondary chickenpox.

PMID- 25950466
TI  - Peptides derived from the dependence receptor ALK are proapoptotic for ALK
      positive tumors.
AB  - ALK is a receptor tyrosine kinase with an oncogenic role in various types of
      human malignancies. Despite constitutive activation of the kinase through gene
      alterations, such as chromosomal translocation, gene amplification or mutation,
      treatments with kinase inhibitors invariably lead to the development of
      resistance. Aiming to develop new tools for ALK targeting, we took advantage of
      our previous demonstration identifying ALK as a dependence receptor, implying
      that in the absence of ligand the kinase-inactive ALK triggers or enhances
      apoptosis. Here, we synthesized peptides mimicking the proapoptotic domain of ALK
      and investigated their biological effects on tumor cells. We found that an ALK
      derived peptide of 36 amino acids (P36) was cytotoxic for ALK-positive anaplastic
      large-cell lymphoma and neuroblastoma cell lines. In contrast, ALK-negative tumor
      cells and normal peripheral blood mononuclear cells were insensitive to P36. The
      cytotoxic effect was due to caspase-dependent apoptosis and required N
      myristoylation of the peptide. Two P36-derived shorter peptides as well as a
      cyclic peptide also induced apoptosis. Surface plasmon resonance and mass
      spectrometry analysis of P36-interacting proteins from two responsive cell lines,
      Cost lymphoma and SH-SY5Y neuroblastoma, uncovered partners that could involve
      p53-dependent signaling and pre-mRNA splicing. Furthermore, siRNA-mediated
      knockdown of p53 rescued these cells from P36-induced apoptosis. Finally, we
      observed that a treatment combining P36 with the ALK-specific inhibitor
      crizotinib resulted in additive cytotoxicity. Therefore, ALK-derived peptides
      could represent a novel targeted therapy for ALK-positive tumors. 

PMID- 25950467
TI  - Wallenda regulates JNK-mediated cell death in Drosophila.
AB  - The c-Jun N-terminal kinase (JNK) pathway plays essential roles in regulating a
      variety of cellular processes including proliferation, migration and survival.
      Previous genetic studies in Drosophila have identified numerous cell death
      regulating genes, providing new insights into the mechanisms for related
      diseases. Despite the known role of the small GTPase Rac1 in regulating cell
      death, the downstream components and underlying mechanism remain largely elusive.
      Here, we show that Rac1 promotes JNK-dependent cell death through Wallenda (Wnd).
      In addition, we find that Wnd triggers JNK activation and cell death via its
      kinase domain. Moreover, we show that both MKK4 and Hep are critical for Wnd
      induced cell death. Furthermore, Wnd is essential for ectopic Egr- or Rho1
      induced JNK activation and cell death. Finally, Wnd is physiologically required
      for loss of scribble-induced JNK-dependent cell death. Thus, our data suggest
      that wnd encodes a novel essential cell death regulator in Drosophila. 

PMID- 25950468
TI  - PD-1 and Tim-3 pathways are associated with regulatory CD8+ T-cell function in
      decidua and maintenance of normal pregnancy.
AB  - CD8+ T cells are critical in the balance between fetal tolerance and antiviral
      immunity. T-cell immunoglobulin mucin-3 (Tim-3) and programmed cell death-1 (PD
      1) are important negative immune regulatory molecules involved in viral
      persistence and tumor metastasis. Here, we demonstrate that Tim-3+PD-1+CD8+ T
      cells from decidua greatly outnumbered those from peripheral blood during human
      early pregnancy. Co-culture of trophoblasts with CD8+ T cells upregulated PD-1+
      and/or Tim-3+ immune cells. Furthermore, the population of CD8+ T cells co
      expressing PD-1 and Tim-3 was enriched within the intermediate memory subset in
      decidua. This population exhibited high proliferative activity and Th2-type
      cytokine producing capacity. Blockade of Tim-3 and PD-1 resulted in decreased in
      vitro proliferation and Th2-type cytokine production while increased trophoblast
      killing and IFN-gamma producing capacities of CD8+ T cells. Pregnant CBA/J
      females challenged with Tim-3 and/or PD-1 blocking antibodies were more
      susceptible to fetal loss, which was associated with CD8+ T-cell dysfunction.
      Importantly, the number and function of Tim-3+PD-1+CD8+ T cells in decidua were
      significantly impaired in miscarriage. These findings underline the important
      roles of Tim-3 and PD-1 pathways in regulating decidual CD8+ T-cell function and
      maintaining normal pregnancy.

PMID- 25950469
TI  - Impairment of enzymatic antioxidant defenses is associated with bilirubin-induced
      neuronal cell death in the cerebellum of Ugt1 KO mice.
AB  - Severe hyperbilirubinemia is toxic during central nervous system development.
      Prolonged and uncontrolled high levels of unconjugated bilirubin lead to
      bilirubin-induced encephalopathy and eventually death by kernicterus. Despite
      extensive studies, the molecular and cellular mechanisms of bilirubin toxicity
      are still poorly defined. To fill this gap, we investigated the molecular
      processes underlying neuronal injury in a mouse model of severe neonatal
      jaundice, which develops hyperbilirubinemia as a consequence of a null mutation
      in the Ugt1 gene. These mutant mice show cerebellar abnormalities and hypoplasia,
      neuronal cell death and die shortly after birth because of bilirubin
      neurotoxicity. To identify protein changes associated with bilirubin-induced cell
      death, we performed proteomic analysis of cerebella from Ugt1 mutant and wild
      type mice. Proteomic data pointed-out to oxidoreductase activities or antioxidant
      processes as important intracellular mechanisms altered during bilirubin-induced
      neurotoxicity. In particular, they revealed that down-representation of DJ-1,
      superoxide dismutase, peroxiredoxins 2 and 6 was associated with
      hyperbilirubinemia in the cerebellum of mutant mice. Interestingly, the reduction
      in protein levels seems to result from post-translational mechanisms because we
      did not detect significant quantitative differences in the corresponding mRNAs.
      We also observed an increase in neuro-specific enolase 2 both in the cerebellum
      and in the serum of mutant mice, supporting its potential use as a biomarker of
      bilirubin-induced neurological damage. In conclusion, our data show that
      different protective mechanisms fail to contrast oxidative burst in bilirubin
      affected brain regions, ultimately leading to neurodegeneration. 

PMID- 25950470
TI  - The synergistic interaction between the calcineurin B subunit and IFN-gamma
      enhances macrophage antitumor activity.
AB  - Macrophages are involved in tumor growth and progression. They infiltrate into
      tumors and cause inflammation, which creates a microenvironment favoring tumor
      growth and metastasis. However, certain stimuli may induce macrophages to act as
      tumor terminators. Here we report that the calcineurin B subunit (CnB) synergizes
      with IFN-gamma to make macrophages highly cytotoxic to cancer cells. Furthermore,
      CnB and IFN-gamma act synergistically to polarize mouse tumor-associated
      macrophages, as well as human monocyte-derived macrophages to an M1-like
      phenotype. This synergy is mediated by the crosstalk between CnB-engaged integrin
      alphaM-p38 MAPK signaling and IFN-gamma-initiated p38/PKC-delta/Jak2 signaling.
      Interestingly, the signal transducer and activator of transcription 1 (STAT1) is
      a key factor that orchestrates the synergy of CnB and IFN-gamma, and the
      phosphorylation status at Ser727 and Tyr701 of STAT1 is directly regulated by CnB
      and IFN-gamma. 

PMID- 25950471
TI  - FAS-ligand regulates differential activation-induced cell death of human T-helper
      1 and 17 cells in healthy donors and multiple sclerosis patients.
AB  - Functionally distinct T-helper (Th) subsets orchestrate immune responses.
      Maintenance of homeostasis through the tight control of inflammatory Th cells is
      crucial to avoid autoimmune inflammation. Activation-Induced Cell Death (AICD)
      regulates homeostasis of T cells, and it has never been investigated in human Th
      cells. We generated stable clones of inflammatory Th subsets involved in
      autoimmune diseases, such as Th1, Th17 and Th1/17 cells, from healthy donors (HD)
      and multiple sclerosis (MS) patients and we measured AICD. We find that human Th1
      cells are sensitive, whereas Th17 and Th1/17 are resistant, to AICD. In
      particular, Th1 cells express high level of FAS-ligand (FASL), which interacts
      with FAS and leads to caspases' cleavage and ultimately to cell death. In
      contrast, low FASL expression in Th17 and Th1/17 cells blunts caspase 8
      activation and thus reduces cell death. Interestingly, Th cells obtained from
      healthy individuals and MS patients behave similarly, suggesting that this
      mechanism could explain the persistence of inflammatory IL-17-producing cells in
      autoimmune diseases, such as MS, where their generation is particularly
      substantial. 

PMID- 25950472
TI  - ErbB2-intronic microRNA-4728: a novel tumor suppressor and antagonist of
      oncogenic MAPK signaling.
AB  - Although the role of the ErbB2/HER2 oncogene in cancers has been extensively
      studied, how ErbB2 is regulated remains poorly understood. A novel microRNA, mir
      4728, was recently found within an intron of the ErbB2 gene. However, the
      function and clinical relevance of this intronic miRNA are completely unknown.
      Here, we demonstrate that mir-4728 is a negative regulator of MAPK signaling
      through directly targeting the ERK upstream kinase MST4 and exerts numerous tumor
      suppressive properties in vitro and in animal models. Importantly, our patient
      sample study shows that mir-4728 was under-expressed in breast tumors compared
      with normal tissue, and loss of mir-4728 correlated with worse overall patient
      survival. These results strongly suggest that mir-4728 is a tumor-suppressive
      miRNA that controls MAPK signaling through targeting MST4, revealing mir-4728's
      significance as a potential prognostic factor and target for therapeutic
      intervention in cancer. Moreover, this study represents a conceptual advance by
      providing strong evidence that a tumor-suppressive miRNA can antagonize the
      canonical signaling of its host oncogene. 

PMID- 25950473
TI  - Antitumour potential of BPT: a dual inhibitor of cdk4 and tubulin polymerization.
AB  - The marine natural product fascaplysin (1) is a potent Cdk4 (cyclin-dependent
      kinase 4)-specific inhibitor, but is toxic to all cell types possibly because of
      its DNA-intercalating properties. Through the design and synthesis of numerous
      fascaplysin analogues, we intended to identify inhibitors of cancer cell growth
      with good therapeutic window with respect to normal cells. Among various non
      planar tryptoline analogues prepared, N-(biphenyl-2-yl) tryptoline (BPT, 6) was
      identified as a potent inhibitor of cancer cell growth and free from DNA-binding
      properties owing to its non-planar structure. This compound was tested in over 60
      protein kinase assays. It displayed inhibition of Cdk4-cyclin D1 enzyme in vitro
      far more potently than many other kinases including Cdk family members. Although
      it blocks growth of cancer cells deficient in the mitotic-spindle checkpoint at
      the G0/G1 phase of the cell cycle, the block occurs primarily at the G2/M phase.
      BPT inhibits tubulin polymerization in vitro and acts as an enhancer of tubulin
      depolymerization of paclitaxel-stabilized tubulin in live cells. Western blot
      analyses indicated that, in p53-positive cells, BPT upregulates the expression of
      p53, p21 and p27 proteins, whereas it downregulates the expression of cyclin B1
      and Cdk1. BPT selectively kills SV40-transformed mouse embryonic hepatic cells
      and human fibroblasts rather than untransformed cells. BPT inhibited the growth
      of several human cancer cells with an IC50<1 MUM. The pharmacokinetic study in
      BALB/c mice indicated good plasma exposure after intravenous administration. It
      was found to be efficacious at 1/10th the maximum-tolerated dose (1000 mg/kg)
      against human tumours derived from HCT-116 (colon) and NCI-H460 (lung) cells in
      SCID (severe-combined immunodeficient) mice models. BPT is a relatively better
      anticancer agent than fascaplysin with an unusual ability to block two
      overlapping yet crucial phases of the cell cycle, mitosis and G0/G1. Its ability
      to effectively halt tumour growth in human tumour-bearing mice would suggest that
      BPT has the potential to be a candidate for further clinical development.

PMID- 25950474
TI  - Uncoupling Neogenin association with lipid rafts promotes neuronal survival and
      functional recovery after stroke.
AB  - The dependence receptor Neogenin and its ligand, the repulsive guidance molecule
      a (RGMa), regulate apoptosis and axonal growth in the developing and the adult
      central nervous system (CNS). Here, we show that this pathway has also a critical
      role in neuronal death following stroke, and that providing RGMa to neurons
      blocks Neogenin-induced death. Interestingly, the Neogenin pro-death function
      following ischemic insult depends on Neogenin association with lipid rafts. Thus,
      a peptide that prevents Neogenin association with lipid rafts increased neuronal
      survival in several in vitro stroke models. In rats, a pro-survival effect was
      also observed in a model of ocular ischemia, as well as after middle cerebral
      artery occlusion (MCAO). Treatments that prevented Neogenin association with
      lipid rafts improved neuronal survival and the complexity of the neuronal network
      following occlusion of the middle artery. Toward the development of a treatment
      for stroke, we developed a human anti-RGMa antibody that also prevents Neogenin
      association with lipid rafts. We show that this antibody also protected CNS
      tissue from ischemic damage and that its application resulted in a significant
      functional improvement even when administrated 6 h after artery occlusion. Thus,
      our results draw attention to the role of Neogenin and lipid rafts as potential
      targets following stroke. 

PMID- 25950475
TI  - Platelet-activating factor induces cell cycle arrest and disrupts the DNA damage
      response in mast cells.
AB  - Platelet-activating factor (PAF) is a potent phospholipid modulator of
      inflammation that has diverse physiological and pathological functions.
      Previously, we demonstrated that PAF has an essential role in ultraviolet (UV)
      induced immunosuppression and reduces the repair of damaged DNA, suggesting that
      UV-induced PAF is contributing to skin cancer initiation by inducing immune
      suppression and also affecting a proper DNA damage response. The exact role of
      PAF in modulating cell proliferation, differentiation or transformation is
      unclear. Here, we investigated the mechanism(s) by which PAF affects the cell
      cycle and impairs early DNA damage response. PAF arrests proliferation in
      transformed and nontransformed human mast cells by reducing the expression of
      cyclin-B1 and promoting the expression of p21. PAF-treated cells show a dose
      dependent cell cycle arrest mainly at G2-M, and a decrease in the DNA damage
      response elements MCPH1/BRIT-1 and ataxia telangiectasia and rad related (ATR).
      In addition, PAF disrupts the localization of p-ataxia telangiectasia mutated (p
      ATM), and phosphorylated-ataxia telangiectasia and rad related (p-ATR) at the
      site of DNA damage. Whereas the potent effect on cell cycle arrest may imply a
      tumor suppressor activity for PAF, the impairment of proper DNA damage response
      might implicate PAF as a tumor promoter. The outcome of these diverse effects may
      be dependent on specific cues in the microenvironment. 

PMID- 25950476
TI  - Geniposide promotes beta-cell regeneration and survival through regulating beta
      catenin/TCF7L2 pathway.
AB  - T-cell factor 7-like 2 (TCF7L2) is an important transcription factor of Wnt/beta
      catenin signaling, which has critical roles in beta-cell survival and
      regeneration. In preliminary screening assay, we found geniposide, a naturally
      occurring compound, was able to increase TCF7L2 mRNA level in Min6 cells. Here we
      aimed to investigate the role of geniposide in beta-cell and underlying mechanism
      involved. Geniposide was found to promote beta-cell survival by increasing beta
      cell proliferation and decreasing beta-cell apoptosis in cultured mouse islets
      after challenge with diabetic stimuli. Geniposide protected beta-cell through
      activating Wnt signaling, enhanced expressions of TCF7L2 and GLP-1R, activated
      AKT, inhibited GSK3beta activity, and promoted beta-catenin nuclear
      translocation. The protective effect of geniposide was remarkably suppressed by
      siRNAs against beta-catenin, or by ICG001 (beta-catenin/TCF-mediated
      transcription inhibitor). Moreover, geniposide promoted beta-cell regeneration in
      vivo to normalize blood glucose in high-fat diet and db/db mice. Increased beta
      cell proliferation was observed in pancreatic sections of geniposide-treated
      diabetic mice. Most importantly, geniposide triggered small islet-like cell
      clusters formation as a result of beta-cell neogenesis from ductal epithelium,
      which was well correlated with the increase in TCF7L2 expression. In exocrine
      cells isolated from mouse pancreas, geniposide could induce duct cell
      differentiation through upregulating TCF7L2 expression and activating JAK2/STAT3
      pathway. Taken together, we identified a novel role of geniposide in promoting
      beta-cell survival and regeneration by mechanisms involving the activation of
      beta-catenin/TCF7L2 signaling. Our finding highlights the potential value of
      geniposide as a possible treatment for type 2 diabetes. 

PMID- 25950477
TI  - Acetylation of HDAC1 and degradation of SIRT1 form a positive feedback loop to
      regulate p53 acetylation during heat-shock stress.
AB  - The tumor suppressor p53 is an essential transcription factor that sensitively
      regulates cellular responses to various stresses. Acetylation, a critically
      important posttranslational modification of p53, is induced in response to
      cellular stresses. P53 acetylation level strongly correlates with protein
      stability and activity. The steady-state level of p53 acetylation is balanced by
      dynamic acetylation and deacetylation. Despite the function of p53 acetylation
      being well studied, how the steady state of p53 acetylation level is regulated in
      response to cellular stresses remains unclear. In particular, the dynamic
      regulation of the deacetylase activities responsible for p53 deacetylation during
      cellular stress is unknown. In the current study, we investigated the dynamic
      regulation of HDAC1 (histone deacetylase 1) and SIRT1 (sirtuin 1), two major
      enzymes for p53 deacetylation, during cell stress. We found that various cell
      stress events induce HDAC1 acetylation. The increased level of HDAC1 acetylation
      correlates with the level of p53 acetylation. Acetylated HDAC1 loses the ability
      to deacetylate p53. Cellular stresses also promote the decline of the SIRT1
      protein in a proteasome-dependent pathway, which also results in the increase of
      p53 acetylation. Importantly, the decreased level of SIRT1 also contributes to
      the accumulation of HDAC1 acetylation as SIRT1 deacetylates HDAC1. Therefore, the
      increase of HDAC1 acetylation and reduced level of SIRT1 protein during cellular
      stress directly link to the induction of p53 acetylation. These results unveil
      the mechanism underlying the dynamic regulation of p53 acetylation during cell
      stress. 

PMID- 25950478
TI  - The p38alpha mitogen-activated protein kinase is a key regulator of myelination
      and remyelination in the CNS.
AB  - The p38alpha mitogen-activated protein kinase (MAPK) is one of the
      serine/threonine kinases regulating a variety of biological processes, including
      cell-type specification, differentiation and migration. Previous in vitro studies
      using pharmacological inhibitors suggested that p38 MAPK is essential for
      oligodendrocyte (OL) differentiation and myelination. To investigate the specific
      roles of p38alpha MAPK in OL development and myelination in vivo, we generated
      p38alpha conditional knockout (CKO) mice under the PLP and nerve/glial antigen 2
      (NG2) gene promoters, as these genes are specifically expressed in OL progenitor
      cells (OPCs). Our data revealed that myelin synthesis was completely inhibited in
      OLs differentiated from primary OPC cultures derived from the NG2 Cre-p38alpha
      CKO mouse brains. Although an in vivo myelination defect was not obvious after
      gross examination of these mice, electron microscopic analysis showed that the
      ultrastructure of myelin bundles was severely impaired. Moreover, the onset of
      myelination in the corpus callosum was delayed in the knockout mice compared with
      p38alpha fl/fl control mice. A delay in OL differentiation in the central nervous
      system was observed with concomitant downregulation in the expression of OPC- and
      OL-specific genes such as Olig1 and Zfp488 during early postnatal development.
      OPC proliferation was not affected during this time. These data indicate that
      p38alpha is a positive regulator of OL differentiation and myelination.
      Unexpectedly, we observed an opposite effect of p38alpha on remyelination in the
      cuprizone-induced demyelination model. The p38alpha CKO mice exhibited better
      remyelination capability compared with p38alpha fl/fl mice following
      demyelination. The opposing roles of p38alpha in myelination and remyelination
      could be due to a strong anti-inflammatory effect of p38alpha or a dual
      reciprocal regulatory action of p38alpha on myelin formation during development
      and on remyelination after demyelination. 

PMID- 25950479
TI  - Ubiquinone-binding site mutagenesis reveals the role of mitochondrial complex II
      in cell death initiation.
AB  - Respiratory complex II (CII, succinate dehydrogenase, SDH) inhibition can induce
      cell death, but the mechanistic details need clarification. To elucidate the role
      of reactive oxygen species (ROS) formation upon the ubiquinone-binding (Qp) site
      blockade, we substituted CII subunit C (SDHC) residues lining the Qp site by site
      directed mutagenesis. Cell lines carrying these mutations were characterized on
      the bases of CII activity and exposed to Qp site inhibitors MitoVES,
      thenoyltrifluoroacetone (TTFA) and Atpenin A5. We found that I56F and S68A SDHC
      variants, which support succinate-mediated respiration and maintain low
      intracellular succinate, were less efficiently inhibited by MitoVES than the wild
      type (WT) variant. Importantly, associated ROS generation and cell death
      induction was also impaired, and cell death in the WT cells was malonate and
      catalase sensitive. In contrast, the S68A variant was much more susceptible to
      TTFA inhibition than the I56F variant or the WT CII, which was again reflected by
      enhanced ROS formation and increased malonate- and catalase-sensitive cell death
      induction. The R72C variant that accumulates intracellular succinate due to
      compromised CII activity was resistant to MitoVES and TTFA treatment and did not
      increase ROS, even though TTFA efficiently generated ROS at low succinate in
      mitochondria isolated from R72C cells. Similarly, the high-affinity Qp site
      inhibitor Atpenin A5 rapidly increased intracellular succinate in WT cells but
      did not induce ROS or cell death, unlike MitoVES and TTFA that upregulated
      succinate only moderately. These results demonstrate that cell death initiation
      upon CII inhibition depends on ROS and that the extent of cell death correlates
      with the potency of inhibition at the Qp site unless intracellular succinate is
      high. In addition, this validates the Qp site of CII as a target for cell death
      induction with relevance to cancer therapy. 

PMID- 25950480
TI  - Arachidonic acid promotes skin wound healing through induction of human MSC
      migration by MT3-MMP-mediated fibronectin degradation.
AB  - Arachidonic acid (AA) is largely released during injury, but it has not been
      fully studied yet how AA modulates wound repair with stem cells. Therefore, we
      investigated skin wound-healing effect of AA-stimulated human umbilical cord
      blood-derived mesenchymal stem cells (hUCB-MSCs) in vivo and its molecular
      mechanism in vitro. We found that transplantation of hUCB-MSCs pre-treated with
      AA enhanced wound filling, re-epithelization, and angiogenesis in a mouse skin
      excisional wound model. AA significantly promoted hUCB-MSCs migration after a 24
      h incubation, which was inhibited by the knockdown of G-protein-coupled receptor
      40 (GPR40). AA activated mammalian target of rapamycin complex 2 (mTORC2) and
      Aktser473 through the GPR40/phosphoinositide 3-kinase (PI3K) signaling, which was
      responsible for the stimulation of an atypical protein kinase C (PKC) isoform,
      PKCzeta. Subsequently, AA stimulated phosphorylation of p38 MAPK and
      transcription factor Sp1, and induced membrane type 3-matrix metalloproteinase
      (MT3-MMP)-dependent fibronectin degradation in promoting hUCB-MSCs motility.
      Finally, the silencing of MT3-MMP in AA-stimulated hUCB-MSCs failed to promote
      the repair of skin wounds owing to impaired cell motility. In conclusion, AA
      enhances skin wound healing through induction of hUCB-MSCs motility by MT3-MMP
      mediated fibronectin degradation, which relies on GPR40-dependent mTORC2
      signaling pathways.

PMID- 25950481
TI  - Gankyrin drives malignant transformation of chronic liver damage-mediated
      fibrosis via the Rac1/JNK pathway.
AB  - Hepatocarcinogenesis is a complex process involving chronic liver injury,
      inflammation, unregulated wound healing, subsequent fibrosis and carcinogenesis.
      To decipher the molecular mechanism underlying transition from chronic liver
      injury to dysplasia, we investigated the oncogenic role of gankyrin (PSMD10 or
      p28GANK) during malignant transformation in a transgenic mouse model. Here, we
      find that gankyrin increased in patients with cirrhosis. In addition to more
      severe liver fibrosis and tumorigenesis after DEN plus CCl4 treatment, hepatocyte
      specific gankyrin-overexpressing mice (gankyrinhep) exhibited malignant
      transformation from liver fibrosis to tumors even under single CCl4
      administration, whereas wild-type mice merely experienced fibrosis. Consistently,
      enhanced hepatic injury, severe inflammation and strengthened compensatory
      proliferation occurred in gankyrinhep) mice during CCl4 performance. This
      correlated with augmented expressions of cell cycle-related genes and abnormal
      activation of Rac1/c-jun N-terminal kinase (JNK). Pharmacological inhibition of
      the Rac1/JNK pathway attenuated hepatic fibrosis and prevented CCl4-induced
      carcinogenesis in gankyrinhep mice. Together, these findings suggest that
      gankyrin promotes liver fibrosis/cirrhosis progression into hepatocarcinoma
      relying on a persistent liver injury and inflammatory microenvironment. Blockade
      of Rac1/JNK activation impeded gankyrin-mediated hepatocytic malignant
      transformation, indicating the combined inhibition of gankyrin and Rac1/JNK as a
      potential prevention mechanism for cirrhosis transition.

PMID- 25950483
TI  - Identification of thioridazine, an antipsychotic drug, as an antiglioblastoma and
      anticancer stem cell agent using public gene expression data.
AB  - Glioblastoma (GBM) is a common and malignant tumor with a poor prognosis.
      Glioblastoma stem cells (GSCs) have been reported to be involved in
      tumorigenesis, tumor maintenance and therapeutic resistance. Thus, to discover
      novel candidate therapeutic drugs for anti-GBM and anti-GSCs is an urgent need.
      We hypothesized that if treatment with a drug could reverse, at least in part,
      the gene expression signature of GBM and GSCs, this drug may have the potential
      to inhibit pathways essential in the formation of GBM and thereby treat GBM.
      Here, we collected 356 GBM gene signatures from public databases and queried the
      Connectivity Map. We systematically evaluated the in vitro antitumor effects of
      79 drugs in GBM cell lines. Of the drugs screened, thioridazine was selected for
      further characterization because it has potent anti-GBM and anti-GSCs properties.
      When investigating the mechanisms underlying the cytocidal effects of
      thioridazine, we found that thioridazine induces autophagy in GBM cell lines, and
      upregulates AMPK activity. Moreover, LC3-II was upregulated in U87MG sphere cells
      treated with thioridazine. In addition, thioridazine suppressed GBM tumorigenesis
      and induced autophagy in vivo. We not only repurposed the antipsychotic drug
      thioridazine as a potent anti-GBM and anti-GSCs agent, but also provided a new
      strategy to search for drugs with anticancer and anticancer stem cell properties.

PMID- 25950482
TI  - Podocyte apoptosis is prevented by blocking the Toll-like receptor pathway.
AB  - High serum lipopolysaccharide (LPS) activity in normoalbuminuric patients with
      type 1 diabetes (T1D) predicts the progression of diabetic nephropathy (DN), but
      the mechanisms behind this remain unclear. We observed that treatment of cultured
      human podocytes with sera from normoalbuminuric T1D patients with high LPS
      activity downregulated 3-phosphoinositide-dependent kinase-1 (PDK1), an activator
      of the Akt cell survival pathway, and induced apoptosis. Knockdown of PDK1 in
      cultured human podocytes inhibited antiapoptotic Akt pathway, stimulated
      proapoptotic p38 MAPK pathway, and increased apoptosis demonstrating an
      antiapoptotic role for PDK1 in podocytes. Interestingly, PDK1 was downregulated
      in the glomeruli of diabetic rats and patients with type 2 diabetes before the
      onset of proteinuria, further suggesting that reduced expression of PDK1
      associates with podocyte injury and development of DN. Treatment of podocytes in
      vitro and mice in vivo with LPS reduced PDK1 expression and induced apoptosis,
      which were prevented by inhibiting the Toll-like receptor (TLR) signaling pathway
      with the immunomodulatory agent GIT27. Our data show that LPS downregulates the
      cell survival factor PDK1 and induces podocyte apoptosis, and that blocking the
      TLR pathway with GIT27 may provide a non-nephrotoxic means to prevent the
      progression of DN. 

PMID- 25950484
TI  - Myocardial MiR-30 downregulation triggered by doxorubicin drives alterations in
      beta-adrenergic signaling and enhances apoptosis.
AB  - The use of anthracyclines such as doxorubicin (DOX) has improved outcome in
      cancer patients, yet associated risks of cardiomyopathy have limited their
      clinical application. DOX-associated cardiotoxicity is frequently irreversible
      and typically progresses to heart failure (HF) but our understanding of molecular
      mechanisms underlying this and essential for development of cardioprotective
      strategies remains largely obscure. As microRNAs (miRNAs) have been shown to play
      potent regulatory roles in both cardiovascular disease and cancer, we
      investigated miRNA changes in DOX-induced HF and the alteration of cellular
      processes downstream. Myocardial miRNA profiling was performed after DOX-induced
      injury, either via acute application to isolated cardiomyocytes or via chronic
      exposure in vivo, and compared with miRNA profiles from remodeled hearts
      following myocardial infarction. The miR-30 family was downregulated in all three
      models. We describe here that miR-30 act regulating the beta-adrenergic pathway,
      where preferential beta1- and beta2-adrenoceptor (beta1AR and beta2AR) direct
      inhibition is combined with Gialpha-2 targeting for fine-tuning. Importantly, we
      show that miR-30 also target the pro-apoptotic gene BNIP3L/NIX. In aggregate, we
      demonstrate that high miR-30 levels are protective against DOX toxicity and
      correlate this in turn with lower reactive oxygen species generation. In
      addition, we identify GATA-6 as a mediator of DOX-associated reductions in miR-30
      expression. In conclusion, we describe that DOX causes acute and sustained miR-30
      downregulation in cardiomyocytes via GATA-6. miR-30 overexpression protects
      cardiac cells from DOX-induced apoptosis, and its maintenance represents a
      potential cardioprotective and anti-tumorigenic strategy for anthracyclines. 

PMID- 25950485
TI  - Mcl-1 is a key regulator of the ovarian reserve.
AB  - A majority of ovarian follicles are lost to natural death, but the disruption of
      factors involved in maintenance of the oocyte pool results in a further untimely
      follicular depletion known as premature ovarian failure. The anti-apoptotic B
      cell lymphoma 2 (Bcl-2) family member myeloid cell leukemia-1 (MCL-1) has a pro
      survival role in various cell types; however, its contribution to oocyte survival
      is unconfirmed. We present a phenotypic characterization of oocytes deficient in
      Mcl-1, and establish its role in maintenance of the primordial follicle (PMF)
      pool, growing oocyte survival and oocyte quality. Mcl-1 depletion resulted in the
      premature exhaustion of the ovarian reserve, characterized by early PMF loss
      because of activation of apoptosis. The increasingly diminished surviving cohort
      of growing oocytes displayed elevated markers of autophagy and mitochondrial
      dysfunction. Mcl-1-deficient ovulated oocytes demonstrated an increased
      susceptibility to cellular fragmentation with activation of the apoptotic
      cascade. Concomitant deletion of the pro-apoptotic Bcl-2 member Bcl-2-associated
      X protein (Bax) rescued the PMF phenotype and ovulated oocyte death, but did not
      prevent the mitochondrial dysfunction associated with Mcl-1 deficiency and could
      not rescue long-term breeding performance. We thus recognize MCL-1 as the
      essential survival factor required for conservation of the postnatal PMF pool,
      growing follicle survival and effective oocyte mitochondrial function. 

PMID- 25950486
TI  - Neuronal developmental gene and miRNA signatures induced by histone deacetylase
      inhibitors in human embryonic stem cells.
AB  - Human embryonic stem cells (hESCs) may be applied to develop human-relevant
      sensitive in vitro test systems for monitoring developmental toxicants. The aim
      of this study was to identify potential developmental toxicity mechanisms of the
      histone deacetylase inhibitors (HDAC) valproic acid (VPA), suberoylanilide
      hydroxamic acid (SAHA) and trichostatin A (TSA) relevant to the in vivo condition
      using a hESC model in combination with specific differentiation protocols and
      genome-wide gene expression and microRNA profiling. Analysis of the gene
      expression data showed that VPA repressed neural tube and dorsal forebrain (OTX2,
      ISL1, EMX2 and SOX10)-related transcripts. In addition, VPA upregulates
      axonogenesis and ventral forebrain-associated genes, such as SLIT1, SEMA3A,
      DLX2/4 and GAD2. HDACi-induced expression of miR-378 and knockdown of miR-378
      increases the expression of OTX2 and EMX2, which supports our hypothesis that
      HDACi targets forebrain markers through miR-378. In conclusion, multilineage
      differentiation in vitro test system is very sensitive for monitoring molecular
      activities relevant to in vivo neuronal developmental toxicity. Moreover, miR-378
      seems to repress the expression of the OTX2 and EMX2 and therefore could be a
      regulator of the development of neural tube and dorsal forebrain neurons. 

PMID- 25950487
TI  - Inhibition of autophagy sensitizes malignant pleural mesothelioma cells to dual
      PI3K/mTOR inhibitors.
AB  - Malignant pleural mesothelioma (MPM) originates in most of the cases from chronic
      inflammation of the mesothelium due to exposure to asbestos fibers. Given the
      limited effect of chemotherapy, a big effort is being made to find new treatment
      options. The PI3K/mTOR pathway was reported to be upregulated in MPM. We tested
      the cell growth inhibition properties of two dual PI3K/mTOR inhibitors NVP-BEZ235
      and GDC-0980 on 19 MPM cell lines. We could identify resistant and sensitive
      lines; however, there was no correlation to the downregulation of PI3K/mTOR
      activity markers. As a result of mTOR inhibition, both drugs efficiently induced
      long-term autophagy but not cell death. Autophagy blockade by chloroquine in
      combination with the dual PI3K/mTOR inhibitors significantly induced caspase
      independent cell death involving RIP1 in the sensitive cell line SPC212. Cell
      death in the resistant cell line Mero-82 was less pronounced, and it was not
      induced via RIP1-dependent mechanism, suggesting the involvement of RIP1
      downstream effectors. Cell death induction was confirmed in 3D systems. Based on
      these results, we identify autophagy as one of the main mechanisms of cell death
      resistance against dual PI3K/mTOR inhibitors in MPM. As PI3K/mTOR inhibitors are
      under investigation in clinical trials, these results may help interpreting their
      outcome and suggest ways for intervention. 

PMID- 25950488
TI  - IPS-1 differentially induces TRAIL, BCL2, BIRC3 and PRKCE in type I interferons
      dependent and -independent anticancer activity.
AB  - RIG-I-like receptors are the key cytosolic sensors for RNA viruses and induce the
      production of type I interferons (IFN) and pro-inflammatory cytokines through a
      sole adaptor IFN-beta promoter stimulator-1 (IPS-1) (also known as Cardif, MAVS
      and VISA) in antiviral innate immunity. These sensors also have a pivotal role in
      anticancer activity through induction of apoptosis. However, the mechanism for
      their anticancer activity is poorly understood. Here, we show that anticancer
      vaccine adjuvant, PolyIC (primarily sensed by MDA5) and the oncolytic virus,
      Newcastle disease virus (NDV) (sensed by RIG-I), induce anticancer activity. The
      ectopic expression of IPS-1 into type I IFN-responsive and non-responsive cancer
      cells induces anticancer activity. PolyIC transfection and NDV infection
      upregulate pro-apoptotic gene TRAIL and downregulate the anti-apoptotic genes
      BCL2, BIRC3 and PRKCE. Furthermore, stable knockdown of IPS-1, IRF3 or IRF7 in
      IFN-non-responsive cancer cells show reduced anticancer activity by suppressing
      apoptosis via TRAIL and anti-apoptotic genes. Collectively, our study shows that
      IPS-1 induces anticancer activity through upregulation of pro-apoptotic gene
      TRAIL and downregulation of the anti-apoptotic genes BCL2, BIRC3 and PRKCE via
      IRF3 and IRF7 in type I IFN-dependent and -independent manners. 

PMID- 25950490
TI  - Dark CPDs and photocarcinogenesis: the party continues after the lights go out.

PMID- 25950489
TI  - Divergent effects of RIP1 or RIP3 blockade in murine models of acute liver
      injury.
AB  - Necroptosis is a recently described Caspase 8-independent method of cell death
      that denotes organized cellular necrosis. The roles of RIP1 and RIP3 in mediating
      hepatocyte death from acute liver injury are incompletely defined. Effects of
      necroptosis blockade were studied by separately targeting RIP1 and RIP3 in
      diverse murine models of acute liver injury. Blockade of necroptosis had
      disparate effects on disease outcome depending on the precise etiology of liver
      injury and component of the necrosome targeted. In ConA-induced autoimmune
      hepatitis, RIP3 deletion was protective, whereas RIP1 inhibition exacerbated
      disease, accelerated animal death, and was associated with increased hepatocyte
      apoptosis. Conversely, in acetaminophen-mediated liver injury, blockade of either
      RIP1 or RIP3 was protective and was associated with lower NLRP3 inflammasome
      activation. Our work highlights the fact that diverse modes of acute liver injury
      have differing requirements for RIP1 and RIP3; moreover, within a single injury
      model, RIP1 and RIP3 blockade can have diametrically opposite effects on tissue
      damage, suggesting that interference with distinct components of the necrosome
      must be considered separately. 

PMID- 25950491
TI  - The physician-scientist workforce in the United States.

PMID- 25950492
TI  - Fibroblast growth factor family aberrations in cancers: clinical and molecular
      characteristics.
AB  - Fibroblast growth factor ligands and receptors (FGF and FGFR) play critical roles
      in tumorigenesis, and several drugs have been developed to target them. We report
      the biologic correlates of FGF/FGFR abnormalities in diverse malignancies. The
      medical records of patients with cancers that underwent targeted next generation
      sequencing (182 or 236 cancer-related genes) were reviewed. The following
      FGF/FGFR genes were tested: FGF3, 4, 6, 7, 10, 12, 14, 19, 23 and FGFR1, 2, 3,
      and 4. Of 391 patients, 56 (14.3%) had aberrant FGF (N = 38, all amplifications)
      and/or FGFR (N = 22 including 5 mutations and one FGFR3-TACC3 fusion). FGF/FGFR
      aberrations were most frequent in breast cancers (26/81, 32.1%, p = 0.0003). In
      multivariate analysis, FGF/FGFR abnormalities were independently associated with
      CCND1/2, RICTOR, ZNF703, RPTOR, AKT2, and CDK8 alterations (all P < 0.02), as
      well as with an increased median number of alterations (P < 0.0001). FGF3, FGF4,
      FGF19 and CCND1 were co-amplified in 22 of 391 patients (5.6%, P < 0.0001), most
      likely because they co-localize on the same chromosomal region (11q13). There was
      no significant difference in time to metastasis or overall survival when
      comparing patients harboring FGF/FGFR alterations versus those not. Overall,
      FGF/FGFR was one of the most frequently aberrant pathways in our population
      comprising patients with diverse malignancies. These aberrations frequently co
      exist with anomalies in a variety of other genes, suggesting that tailored
      combination therapy may be necessary in these patients.

PMID- 25950493
TI  - Intracranial pressure and cerebral perfusion pressure during apnoea testing for
      the diagnosis of brain death - an observational study.
AB  - BACKGROUND AND PURPOSE: Some authors have suggested a rise of intracranial
      pressure (ICP) during apnoea testing and the possibility of harm to patients.
      Data, however, have yet to be obtained. METHODS: Between October 2012 and May
      2014 an observational study was performed on patients who received ICP
      measurements and who underwent brain death diagnosis. ICP, cerebral perfusion
      pressure (CPP), mean arterial blood pressure (MAP) and heart rate were recorded
      continuously from 15 min before the start of brain death diagnosis (baseline),
      during clinical examination including apnoea testing, until 15 min after this
      procedure. RESULTS: A total of 16 clinical examinations for brain death including
      apnoea testing were performed on 13 patients. All patients had primary brain
      lesions. Mean ICP and mean CPP during the examination were 95 +/- 27.7 mmHg and
      13.5 +/- 20.7 mmHg, respectively. ICP and MAP showed a strong and statistically
      significant correlation, with Pearson's correlation coefficients of more than
      +0.6 or less than -0.6 in 13 of the 15 examinations. CONCLUSION: Mean ICP even
      before brain death determination is increased excessively. Changes of ICP during
      apnoea show a clear correlation to the changes of MAP. Furthermore, CPP during
      the condition of brain death may not equal zero but may be positive thereby
      indicating some minor net influx of blood into the brain in some patients.

PMID- 25950494
TI  - Characteristic expression of p57/Kip2 in balloon cells in focal cortical
      dysplasia.
AB  - Balloon cells are a pathognomonic cellular feature of various cortical
      malformations, including focal cortical dysplasia type IIb (FCD IIb), cortical
      tubers of tuberous sclerosis (TSC) and hemimegalencephaly (HME). In the present
      study, we investigated the immunohistochemical expression of p57/Kip2, a member
      of the Cip/Kip family of cyclin-dependent kinase inhibitory proteins, in balloon
      cells in surgical specimens taken from 26, 17 and six patients with FCD IIb, TSC
      and HME, respectively. Characteristic dot-like reactivity with a faint, intense,
      reticular and process-like pattern was confined to the proximal portion of the
      cytoplasmic processes of the cells. Immunoelectron microscopy revealed the
      p57/Kip2 reactivity on intermediate filaments in the proximal portion of the
      processes. The immunohistochemical profile appeared similar to that of CD34;
      however, a double immunofluorescence study demonstrated that no cells showed
      reactivity for both p57/Kip2 and CD34. The frequencies of the p57/Kip2-positive
      cells in FCD IIb and HME were significantly higher than those in TSC, suggesting
      that the balloon cells may be heterogeneous. These findings suggest some
      functional significance of the protein on the cytoplasmic processes of balloon
      cells and appear consistent with the notion that the cells are abnormally
      differentiated progenitor cells.

PMID- 25950495
TI  - Cooperative Effect of Monopodal Silica-Supported Niobium Complex Pairs Enhancing
      Catalytic Cyclic Carbonate Production.
AB  - Recent discoveries highlighted the activity and the intriguing mechanistic
      features of NbCl5 as a molecular catalyst for the cycloaddition of CO2 and
      epoxides under ambient conditions. This has inspired the preparation of novel
      silica-supported Nb species by reacting a molecular niobium precursor,
      [NbCl5.OEt2], with silica dehydroxylated at 700  degrees C (SiO(2-700)) or at 200
      degrees C (SiO(2-200)) to generate diverse surface complexes. The product of the
      reaction between SiO(2-700) and [NbCl5.OEt2] was identified as a monopodal
      supported surface species, [=SiONbCl4.OEt2] (1a). The reactions of SiO(2-200)
      with the niobium precursor, according to two different protocols, generated
      surface complexes 2a and 3a, presenting significant, but different, populations
      of the monopodal surface complex along with bipodal [(=SiO)2NbCl3.OEt2]. (93)Nb
      solid-state NMR spectra of 1a-3a and (31)P solid-state NMR on their PMe3
      derivatives 1b-3b led to the unambiguous assignment of 1a as a single-site
      monopodal Nb species, while 2a and 3a were found to present two distinct surface
      supported components, with 2a being mostly monopodal [=SiONbCl4.OEt2] and 3a
      being mostly bipodal [(=SiO)2NbCl3.OEt2]. A double-quantum/single-quantum (31)P
      NMR correlation experiment carried out on 2b supported the existence of vicinal
      Nb centers on the silica surface for this species. 1a-3a were active
      heterogeneous catalysts for the synthesis of propylene carbonate from CO2 and
      propylene oxide under mild catalytic conditions; the performance of 2a was found
      to significantly surpass that of 1a and 3a. With the support of a systematic DFT
      study carried out on model silica surfaces, the observed differences in catalytic
      efficiency were correlated with an unprecedented cooperative effect between two
      neighboring Nb centers on the surface of 2a. This is in an excellent agreement
      with our previous discoveries regarding the mechanism of NbCl5-catalyzed
      cycloaddition in the homogeneous phase.

PMID- 25950496
TI  - Influence of temperature, anions and size distribution on the zeta potential of
      DMPC, DPPC and DMPE lipid vesicles.
AB  - The purpose of the work is to compare the influence of the multilamellarity,
      phase state, lipid head groups and ionic media on the origin of the surface
      potential of lipid membranes. With this aim, we present a new analysis of the
      zeta potential of multilamellar and unilamellar vesicles composed by
      phosphatidylcholines (PC) and phosphatidylethanolamines (PE) dispersed in water
      and ionic solutions of polarizable anions, at temperatures below and above the
      phase transition. In general, the adsorption of anions seems to explain the
      origin of the zeta potential in vesicles only above the transition temperature
      (Tc). In this case, the sign of the surface potential is ascribed to a partial
      orientation of head group moiety toward the aqueous phase. This is noticeable in
      PC head groups but not in PEs, due to the strong lateral interaction between PO
      and NH group in PE. 

PMID- 25950497
TI  - Flagella but not type IV pili are involved in the initial adhesion of Pseudomonas
      aeruginosa PAO1 to hydrophobic or superhydrophobic surfaces.
AB  - Over the last decades, surface biocontamination has become a major concern in
      food industries and medical environments where its outcomes could vary from
      financial losses to public health issues. Understanding adhesion mechanisms of
      involved microorganisms is essential to develop new strategies of prevention and
      control. Adhesion of Pseudomonas aeruginosa, a nosocomial pathogenic bacterium,
      relies on several bacterial features, among which are bacterial appendages such
      as flagella and type IV pili. Here, we examine the role of P. aeruginosa PAO1
      flagella and type IV pili in the adhesion to abiotic surfaces with various
      hydrophobicities. Adhesion kinetics showed, that after 60min, flagella increased
      the adhesion of the strain to surfaces with high hydrophobicity while no effect
      was observed on hydrophilic surfaces. Flagella of adherent bacteria exhibited
      specific and conserved pattern on the surfaces that suggested a higher affinity
      of flagella for hydrophobic surfaces. Based on these results and on previous
      studies in the literature, we proposed a model of flagella-mediated adhesion onto
      hydrophobic surfaces where these appendages induce the first contact and promote
      the adhesion of the bacterial body. These findings suggest that anti-bioadhesive
      surface design should take into consideration the presence of bacterial
      appendages. 

PMID- 25950498
TI  - Interaction of silver nanoparticles with tethered bilayer lipid membranes.
AB  - Silver nanoparticles are well-known for their antibacterial properties. However,
      the detailed mechanism describing the interaction between the nanoparticles and a
      cell membrane is not fully understood, which can impede the use of the particles
      in biomedical applications. Here, a tethered bilayer lipid membrane has been used
      as a model system to mimic a natural membrane and to study the effect of exposure
      to small silver nanoparticles with diameters of about 2 nm. The solid supported
      membrane architecture allowed for the application of surface analytical
      techniques such as electrochemical impedance spectroscopy and atomic force
      microscopy. Exposure of the membrane to solutions of the silver nanoparticles led
      to a small but completely reversible perturbation of the lipid bilayer. 

PMID- 25950499
TI  - A Unique Alkylation of Azobenzenes with Allyl Acetates by Rh(III)-Catalyzed C-H
      Functionalization.
AB  - A novel Rh(III)-catalyzed direct alkylation of azobenzenes with allyl acetates
      through C-H activation and functionalization is demonstrated in which the allyl
      acetates serve as unique alkylation agents. The rhodium-catalyzed alkylation
      provides a highly efficient and atom-economic approach to a series of azo
      compounds. 

PMID- 25950500
TI  - Brentuximab vedotin compared with other therapies in relapsed/refractory Hodgkin
      lymphoma post autologous stem cell transplant: median overall survival meta
      analysis.
AB  - OBJECTIVE: This meta-analysis compared the median overall survival (mOS) of
      brentuximab vedotin reported in the pivotal phase 2 study with published results
      of other therapies for the treatment of relapsed/refractory (R/R) Hodgkin
      lymphoma (HL) post autologous stem cell transplant (ASCT). RESEARCH DESIGN AND
      METHODS: A systematic literature review identified studies that reported survival
      outcomes following conventional/experimental therapies in R/R HL patients, with
      >=50% having failed >=1 ASCT. Kaplan-Meier curves were used to reconstruct
      individual patient level survival data. Patients were grouped by treatment type
      and reconstructed data were used to estimate the mOS. Censored median regression
      modeling was used to compare mOS in each group with the mOS in the pivotal
      brentuximab vedotin trial. All patients in the pivotal trial had undergone ASCT,
      therefore a sensitivity analysis was conducted among studies with a 100% post
      ASCT patient population. RESULTS: The mOS reported for brentuximab vedotin was
      40.5 (95% CI 30.8-NA) compared with 26.4 months (95% CI 23.5-28.5) across all 40
      studies identified (n = 2518 excluding the brentuximab vedotin trial) (p <
      0.0001). The difference in mOS between brentuximab vedotin and chemotherapy,
      allogeneic stem cell transplant (allo-SCT), and other therapies, was 17.7 (95% CI
      10.6-24.7; p < 0.0001), 12.5 (95% CI 8.2-16.9; p < 0.0001), and 15.2 months (95%
      CI 4.9-25.5; p = 0.0037), respectively. For the 11 studies reporting a 100% prior
      ASCT rate (n = 662 excluding the brentuximab vedotin trial), the mOS was 28.1
      months (95% CI 23.9-34.5), and the difference in mOS between brentuximab vedotin,
      chemotherapy, allo-SCT, and other therapies was 19.0 (95% CI 12.9-25.1; p <
      0.0001), 9.4 (p > 0.05), and 6.8 months (95% CI 1.2-12.5; p = 0.0018),
      respectively. CONCLUSIONS: While some selection bias may occur when comparing
      trials with heterogeneous eligibility criteria, in the absence of randomized
      controlled trial data these results suggest brentuximab vedotin improves long
      term survival and is associated with longer mOS in R/R HL post-ASCT compared with
      other therapies.

PMID- 25950501
TI  - Relative contribution of set cathode potential and external mass transport on TCE
      dechlorination in a continuous-flow bioelectrochemical reactor.
AB  - Microbial bioelectrochemical systems, which use solid-state cathodes to drive the
      reductive degradation of contaminants such as the chlorinated hydrocarbons, are
      recently attracting considerable attention for bioremediation applications. So
      far, most of the published research has focused on analyzing the influence of key
      (bio)electrochemical factors influencing contaminant degradation, such as the
      cathode potential, whereas only few studies have examined the potential impact of
      mass transport phenomena on process performance. Here we analyzed the performance
      of a flow-through bioelectrochemical reactor, continuously fed with a synthetic
      groundwater containing trichloroethene at three different linear fluid velocities
      (from 0.3 m d(-1) to 1.7 m d(-1)) and three different set cathode potentials
      (from -250 mV to -450 mV vs. the standard hydrogen electrode). The obtained
      results demonstrated that, in the range of fluid velocities which are
      characteristics for natural groundwater systems, mass transport phenomena may
      strongly influence the rate and extent of reductive dechlorination. Nonetheless,
      the relative importance of mass transport largely depends on the applied cathode
      potential which, in turn, controls the intrinsic kinetics of biological reactions
      and the underlying electron transfer mechanisms.

PMID- 25950502
TI  - Temperature and recent trends in the chemistry of continental surface ozone.

PMID- 25950504
TI  - The Relevance of Phosphorus and Iron Chemistry to the Recovery of Phosphorus from
      Wastewater: A Review.
AB  - The addition of iron is a convenient way for removing phosphorus from wastewater,
      but this is often considered to limit phosphorus recovery. Struvite precipitation
      is currently used to recover phosphorus, and this approach has attracted much
      interest. However, it requires the use of enhanced biological phosphorus removal
      (EBPR). EBPR is not yet widely applied and the recovery potential is low. Other
      phosphorus recovery methods, including sludge application to agricultural land or
      recovering phosphorus from sludge ash, also have limitations. Energy-producing
      wastewater treatment plants increasingly rely on phosphorus removal using iron,
      but the problem (as in current processes) is the subsequent recovery of
      phosphorus from the iron. In contrast, phosphorus is efficiently mobilized from
      iron by natural processes in sediments and soils. Iron-phosphorus chemistry is
      diverse, and many parameters influence the binding and release of phosphorus,
      including redox conditions, pH, presence of organic substances, and particle
      morphology. We suggest that the current poor understanding of iron and phosphorus
      chemistry in wastewater systems is preventing processes being developed to
      recover phosphorus from iron-phosphorus rich wastes like municipal wastewater
      sludge. Parameters that affect phosphorus recovery are reviewed here, and methods
      are suggested for manipulating iron-phosphorus chemistry in wastewater treatment
      processes to allow phosphorus to be recovered.

PMID- 25950506
TI  - Drug-Induced Self-Assembly of Modified Albumins as Nano-theranostics for Tumor
      Targeted Combination Therapy.
AB  - Paclitaxel (PTX) can bind to human serum albumin (HSA) via hydrophobic
      interaction, forming Abraxane, which is a U.S. Food and Drug Administration (FDA)
      approved effective antitumor nanomedicine drug. Herein, the effective antitumor
      drug PTX is used to induce the self-assembly of HSA modified with either a
      photosensitizer chlorin e6 (Ce6), which at the same time serves as a chelating
      agent for Mn(2+) to enable magnetic resonance imaging, or acyclic Arg-Gly-Asp
      (cRGDyK) peptide that targets alphavbeta3-integrin overexpressed on tumor
      angiogenic endothelium. Two types of tumor-targeting theranostic nanoparticles
      are constructed, either by coassembly of both HSA-Ce6 and HSA-RGD simultaneously
      or by forming an HSA-Ce6@HSA-RGD core-shell structure, with the assistance of PTX
      induced albumin aggregation. Such albumin-based nanoparticles on one hand could
      targetalphavbeta3-integrin, as evidenced by both in vitro and in vivo
      experiments, and on the other hand enable combined photodynamic/chemotherapy,
      which offers remarkably improved therapeutic efficacy to kill cancer in
      comparison to the respective monotherapies. Our work presents a new type of tumor
      targeted multifunctional albumin-based nanoparticles by drug-induced self
      assembly, which is a rather simple method without any sophisticated chemistry or
      materials engineering and is promising for multimodel imaging-guided combination
      therapy of cancer. 

PMID- 25950505
TI  - Occurrence of CYP1B1 Mutations in Juvenile Open-Angle Glaucoma With Advanced
      Visual Field Loss.
AB  - IMPORTANCE: Juvenile open-angle glaucoma (JOAG) is a severe neurodegenerative eye
      disorder in which most of the genetic contribution remains unexplained.
      OBJECTIVE: To assess the prevalence of pathogenic CYP1B1 sequence variants in an
      Australian cohort of patients with JOAG and severe visual field loss. DESIGN,
      SETTING, AND PARTICIPANTS: For this cohort study, we recruited 160 patients with
      JOAG classified as advanced (n = 118) and nonadvanced (n = 42) through the
      Australian and New Zealand Registry of Advanced Glaucoma from January 1, 2007,
      through April 1, 2014. Eighty individuals with no evidence of glaucoma served as
      a control group. We defined JOAG as diagnosis before age 40 years and advanced
      JOAG as visual field loss in 2 of the 4 central fixation squares on a reliable
      visual field test result. We performed direct sequencing of the entire coding
      region of CYP1B1. Data analysis was performed in October 2014. MAIN OUTCOMES AND
      MEASURES: Identification and characterization of CYP1B1 sequence variants.
      RESULTS: We identified 7 different pathogenic variants among 8 of 118 patients
      with advanced JOAG (6.8%) but none among the patients with nonadvanced JOAG.
      Three patients were homozygous or compound heterozygous for CYP1B1 pathogenic
      variants, which provided a likely basis for their disease. Five patients were
      heterozygous. The allele frequency among the patients with advanced JOAG (11 in
      236 [4.7%]) was higher than among our controls (1 in 160 [0.6%]; P = .02; odds
      ratio, 7.8 [95% CI, 0.02-1.0]) or among the control population from the Exome
      Aggregation Consortium database (2946 of 122 960 [2.4%]; P = .02; odds ratio, 2.0
      [95% CI, 0.3-0.9]). Individuals with CYP1B1 pathogenic variants, whether
      heterozygous or homozygous, had worse mean (SD) deviation on visual fields (-24.5
      [5.1] [95% CI, -31.8 to -17.2] vs -15.6 [10.0] [95% CI, -17.1 to -13.6] dB;
      F1,126 = 5.90; P = .02; partial etap2 = 0.05) and were younger at diagnosis (mean
      [SD] age, 23.1 [8.4] [95% CI, 17.2-29.1] vs 31.5 [8.0] [95% CI, 30.1-33.0] years;
      F1,122 = 7.18; P = .008; etap2 = 0.06) than patients without CYP1B1 pathogenic
      variants. CONCLUSIONS AND RELEVANCE: Patients with advanced JOAG based on visual
      field loss had enrichment of CYP1B1 pathogenic variants and a more severe
      phenotype compared with unaffected controls and patients with nonadvanced JOAG.

PMID- 25950503
TI  - Long-term Efficacy of Topical Fluorouracil Cream, 5%, for Treating Actinic
      Keratosis: A Randomized Clinical Trial.
AB  - IMPORTANCE: Topical fluorouracil was demonstrated to be effective in reducing the
      number of actinic keratoses (AKs) for up to 6 months, but no randomized trials
      studied its long-term efficacy. OBJECTIVE: To evaluate the long-term efficacy of
      a single course of fluorouracil cream, 5%, for AK treatment. DESIGN, SETTING, AND
      PARTICIPANTS: The Veterans Affairs Keratinocyte Carcinoma Chemoprevention (VAKCC)
      trial was a randomized, double-blinded, placebo-controlled trial with patients
      from dermatology clinics at 12 VA medical centers recruited from 2009 to 2011 and
      followed up until 2013. Our study population comprised 932 veterans with 2 or
      more keratinocyte carcinomas in the 5 years prior to enrollment. The mean follow
      up duration was 2.6 years in both treatment and control groups. INTERVENTIONS:
      Participants applied either topical fluorouracil cream, 5% (n = 468), or vehicle
      control cream (n = 464) to the face and ears twice daily for up to 4 weeks. MAIN
      OUTCOMES AND MEASURES: This study reports on AK counts and treatments, which were
      secondary outcomes of the VAKCC trial. Actinic keratoses on the face and ears
      were counted by study dermatologists at enrollment and at study visits every 6
      months. The number of spot treatments for AKs on the face and ears at semiannual
      study visits and in between study visits was recorded. RESULTS: The number of AKs
      on the face and ears per participant was not different between the fluorouracil
      and control groups at randomization (11.1 vs 10.6, P > .10). After randomization,
      the fluorouracil group had fewer AKs compared with the control group at 6 months
      (3.0 vs 8.1, P < .001) and for the overall study duration (P < .001). The
      fluorouracil group also had higher complete AK clearance rates (38% vs 17% at 6
      months) and fewer spot treatments at 6-month intervals, at study visits, and in
      between study visits during the trial (P < .01 for all). The fluorouracil group
      took longer to require the first spot AK treatment (6.2 months) compared with the
      control group (6.0 months) (hazard ratio, 0.69; 95% CI, 0.60-0.79). The number of
      hypertrophic AKs was not different between the 2 groups overall (P = .60),
      although there were fewer hypertrophic AKs in the fluorouracil group at 6 months
      (0.23 vs 0.41) (P = .05). CONCLUSIONS AND RELEVANCE: Our results indicate that a
      single course of fluorouracil cream, 5%, effectively reduces AK counts and the
      need for spot treatments for longer than 2 years. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier:NCT00847912.

PMID- 25950508
TI  - Detailed Anatomy of the Cranial Cervical Ganglion in the Dromedary Camel (Camelus
      dromedarius).
AB  - The detailed morphology and topography of the cranial cervical ganglion (CCG)
      with its surrounding structures were studied in 10 sides of five heads of adult
      one-humped camel to determine its general arrangement as well as its differences
      and similarities to other animals. The following detailed descriptions were
      obtained: (1) the bilateral CCG was constantly present caudal to cranial base at
      the rostroventral border of the occipital condyle over the caudolateral part of
      nasopharynx; (2) the CCG was always in close relations medially with the longus
      capitis muscle, rostrolaterally with the internal carotid artery, and caudally
      with the vagus nerve; and (3) the branches of the CCG were the internal carotid
      and external carotid nerves, jugular nerve, cervical interganglionic branch,
      laryngopharyngeal branch, carotid sinus branch and communicating branches to the
      vagus, and first spinal nerves. In conclusion, there was no variation regarding
      topography of dromedary CCG among the specimens, in spite of typical variations
      in number, and mainly in origin of nerve branches ramifying from the CCG. In
      comparative anatomy aspect, the close constant relations, and presence of major
      nerves (internal/external carotid and jugular nerves) of dromedary CCG exhibited
      a typical reported animal's pattern. However, the shape, structures lateral to
      the CCG, the origin and course pattern of external carotid and jugular nerves,
      the number of the major nerves branches, the communicating branches of the CCG to
      the spinal and cranial nerves, and the separation of most rostral parts of
      vagosympathetic trunk of dromedary were different from those of most reported
      animals.

PMID- 25950507
TI  - The Use of a Fully Automated Automatic Adaptive Servoventilation Algorithm in the
      Acute and Long-term Treatment of Central Sleep Apnea.
AB  - BACKGROUND: Central sleep apnea (CSA), in association with obstructive disordered
      breathing, occurs in patients using opioids long-term and those with congestive
      heart failure. In these patients, treatment with CPAP frequently fails. The
      current adaptive servoventilation (ASV) devices are promising for the treatment
      of complex sleep-disordered breathing. These devices use algorithms to
      automatically titrate expiratory and inspiratory pressures. We hypothesized that
      an ASV device operating automatically would significantly reduce the frequency of
      breathing events in patients with mixed sleep apnea during polysomnography and
      with 3 months of treatment. METHODS: This was a prospective, multicenter,
      observational trial. Patients completed 3 nights of attended polysomnography,
      scored at an independent center. Twenty-seven patients with an apnea-hypopnea
      index (AHI) >= 15 and a central apnea index (CAI) >= 5/h underwent automated ASV
      titration without technician intervention. Twenty-six patients (96%) used ASV at
      home for 3 months. RESULTS: Patients had an AHI of 55 +/- 24 (mean +/- SD) and
      CAI of 23 +/- 18 at baseline. Overnight, ASV titration improved AHI, CAI,
      obstructive apnea, and arousal index significantly. Patients reported better
      sleep quality on ASV than CPAP. Over 3 months, ASV remained effective (median AHI
      11 vs four during polysomnography). Mean adherence was 4.2 h per night. Epworth
      Sleepiness Scale decreased from 12.8 to 7.8 (P = .001). CONCLUSIONS: The ASV
      device treated complex breathing disorders using automated algorithms. Compared
      with CPAP, patients reported improved sleep quality. Home use of ASV remained
      effective with acceptable adherence and improvements in daytime sleepiness. TRIAL
      REGISTRY: ClinicalTrials.gov; No.: NCT01199042; URL: www.clinicaltrials.gov.

PMID- 25950509
TI  - RNA Binding Proteins that Control Human Papillomavirus Gene Expression.
AB  - The human papillomavirus (HPV) life cycle is strictly linked to the
      differentiation program of the infected mucosal epithelial cell. In the basal and
      lower levels of the epithelium, early genes coding for pro-mitotic proteins and
      viral replication factors are expressed, while terminal cell differentiation is
      required for activation of late gene expression and production of viral particles
      at the very top of the epithelium. Such productive infections are normally
      cleared within 18-24 months. In rare cases, the HPV infection is stuck in the
      early stage of the infection. Such infections may give rise to cervical lesions
      that can progress to cancer, primarily cancer of the uterine cervix. Since cancer
      progression is strictly linked to HPV gene expression, it is of interest to
      understand how HPV gene expression is regulated. Cis-acting HPV RNA elements and
      cellular RNA-binding proteins control HPV mRNA splicing and polyadenylation.
      These interactions are believed to play a particularly important role in the
      switch from early to late gene expression, thereby contributing to the
      pathogenesis of HPV. Indeed, it has been shown that the levels of various RNA
      binding proteins change in response to differentiation and in response to HPV
      induced cervical lesions and cancer. Here we have compiled published data on RNA
      binding proteins involved in the regulation of HPV gene expression. 

PMID- 25950511
TI  - Michael Addition Catalyzed by Chiral Secondary Amine Phosphoramide Using
      Fluorinated Silyl Enol Ethers: Formation of Quaternary Carbon Stereocenters.
AB  - A chiral secondary amine phosphoramide was developed and identified as a powerful
      catalyst for the Mukaiyama-Michael addition of fluorinated enol silyl ethers to
      tetrasubstituted olefins. The resulting products are obtained with high
      enantioselectivities and contain a quaternary carbon stereocenter bearing either
      a difluoroalkyl or monofluoroalkyl group. 

PMID- 25950510
TI  - Extracellular adenosine generation in the regulation of pro-inflammatory
      responses and pathogen colonization.
AB  - Adenosine, an immunomodulatory biomolecule, is produced by the ecto-enzymes CD39
      (nucleoside triphosphate dephosphorylase) and CD73 (ecto-5'-nucleotidase) by
      dephosphorylation of extracellular ATP. CD73 is expressed by many cell types
      during injury, infection and during steady-state conditions. Besides host cells,
      many bacteria also have CD39-CD73-like machinery, which helps the pathogen
      subvert the host inflammatory response. The major function for adenosine is anti
      inflammatory, and most recent research has focused on adenosine's control of
      inflammatory mechanisms underlying various autoimmune diseases (e.g., colitis,
      arthritis). Although adenosine generated through CD73 provides a feedback to
      control tissue damage mediated by a host immune response, it can also contribute
      to immunosuppression. Thus, inflammation can be a double-edged sword: it may harm
      the host but eventually helps by killing the invading pathogen. The role of
      adenosine in dampening inflammation has been an area of active research, but the
      relevance of the CD39/CD73-axis and adenosine receptor signaling in host defense
      against infection has received less attention. Here, we review our recent
      knowledge regarding CD73 expression during murine Salmonellosis and Helicobacter
      induced gastric infection and its role in disease pathogenesis and bacterial
      persistence. We also explored a possible role for the CD73/adenosine pathway in
      regulating innate host defense function during infection. 

PMID- 25950512
TI  - Engineered catalytic biofilms: Site-specific enzyme immobilization onto E. coli
      curli nanofibers.
AB  - Biocatalytic transformations generally rely on purified enzymes or whole cells to
      perform complex transformations that are used on industrial scale for chemical,
      drug, and biofuel synthesis, pesticide decontamination, and water purification.
      However, both of these systems have inherent disadvantages related to the costs
      associated with enzyme purification, the long-term stability of immobilized
      enzymes, catalyst recovery, and compatibility with harsh reaction conditions. We
      developed a novel strategy for producing rationally designed biocatalytic
      surfaces based on Biofilm Integrated Nanofiber Display (BIND), which exploits the
      curli system of E. coli to create a functional nanofiber network capable of
      covalent immobilization of enzymes. This approach is attractive because it is
      scalable, represents a modular strategy for site-specific enzyme immobilization,
      and has the potential to stabilize enzymes under denaturing environmental
      conditions. We site-specifically immobilized a recombinant alpha-amylase, fused
      to the SpyCatcher attachment domain, onto E. coli curli fibers displaying
      complementary SpyTag capture domains. We characterized the effectiveness of this
      immobilization technique on the biofilms and tested the stability of immobilized
      alpha-amylase in unfavorable conditions. This enzyme-modified biofilm maintained
      its activity when exposed to a wide range of pH and organic solvent conditions.
      In contrast to other biofilm-based catalysts, which rely on high cellular
      metabolism, the modified curli-based biofilm remained active even after cell
      death due to organic solvent exposure. This work lays the foundation for a new
      and versatile method of using the extracellular polymeric matrix of E. coli for
      creating novel biocatalytic surfaces.

PMID- 25950513
TI  - Spectral fingerprinting of individual cells visualized by cavity-reflection
      enhanced light-absorption microscopy.
AB  - The absorption spectrum of light is known to be a "molecular fingerprint" that
      enables analysis of the molecular type and its amount. It would be useful to
      measure the absorption spectrum in single cell in order to investigate the
      cellular status. However, cells are too thin for their absorption spectrum to be
      measured. In this study, we developed an optical-cavity-enhanced absorption
      spectroscopic microscopy method for two-dimensional absorption imaging. The light
      absorption is enhanced by an optical cavity system, which allows the detection of
      the absorption spectrum with samples having an optical path length as small as 10
      MUm, at a subcellular spatial resolution. Principal component analysis of various
      types of cultured mammalian cells indicates absorption-based cellular diversity.
      Interestingly, this diversity is observed among not only different species but
      also identical cell types. Furthermore, this microscopy technique allows us to
      observe frozen sections of tissue samples without any staining and is capable of
      label-free biopsy. Thus, our microscopy method opens the door for imaging the
      absorption spectra of biological samples and thereby detecting the individuality
      of cells. 

PMID- 25950514
TI  - Enantioselective Construction of 3-Hydroxypiperidine Scaffolds by Sequential
      Action of Light and Rhodium upon N-Allylglyoxylamides.
AB  - 3-Hydroxypiperidine scaffolds were enantioselectively constructed in an atom
      economical way by sequential action of light and rhodium upon N
      allylglyoxylamides. In a formal sense, the allylic C-H bond was selectively
      cleaved and enantioselectively added across the ketonic carbonyl group with
      migration of the double bond (carbonyl-ene-type reaction).

PMID- 25950515
TI  - Effects of Two Football Stud Types on Knee and Ankle Kinetics of Single-Leg Land
      Cut and 180 degrees  Cut Movements on Infilled Synthetic Turf.
AB  - Higher ACL injury rates have been recorded in cleats with higher torsional
      resistance in American football, which warrants better understanding of shoe/stud
      dependent joint kinetics. The purpose of this study was to determine differences
      in knee and ankle kinetics during single-leg land cuts and 180 degrees  cuts on
      synthetic infilled turf while wearing 3 types of shoes. Fourteen recreational
      football players performed single-leg land cuts and 180 degrees  cuts in
      nonstudded running shoes (RS) and in football shoes with natural (NTS) and
      synthetic turf studs (STS). Knee and ankle kinetic variables were analyzed with a
      3 * 2 (shoe * movement) repeated-measures ANOVA (P < .05). A significant shoe-by
      movement interaction was found in loading response peak knee adduction moments,
      with NTS producing smaller moments compared with both STS and RS only in 180
      degrees  cuts. Reduced peak negative plantar flexor powers were also found in NTS
      compared with STS. The single-leg land cut produced greater loading response and
      push-off peak knee extensor moments, as well as peak negative and positive
      extensor and plantar flexor powers, but smaller loading peak knee adduction
      moments and push-off peak ankle eversion moments than 180 degrees  cuts. Overall,
      the STS and 180 degrees  cuts resulted in greater frontal plane knee loading and
      should be monitored for possible increased ACL injury risks. 

PMID- 25950516
TI  - Deletion of Metabotropic Glutamate Receptors 2 and 3 (mGlu2 & mGlu3) in Mice
      Disrupts Sleep and Wheel-Running Activity, and Increases the Sensitivity of the
      Circadian System to Light.
AB  - Sleep and/or circadian rhythm disruption (SCRD) is seen in up to 80% of
      schizophrenia patients. The co-morbidity of schizophrenia and SCRD may in part
      stem from dysfunction in common brain mechanisms, which include the glutamate
      system, and in particular, the group II metabotropic glutamate receptors mGlu2
      and mGlu3 (encoded by the genes Grm2 and Grm3). These receptors are relevant to
      the pathophysiology and potential treatment of schizophrenia, and have also been
      implicated in sleep and circadian function. In the present study, we
      characterised the sleep and circadian rhythms of Grm2/3 double knockout (Grm2/3-/
      ) mice, to provide further evidence for the involvement of group II metabotropic
      glutamate receptors in the regulation of sleep and circadian rhythms. We report
      several novel findings. Firstly, Grm2/3-/- mice demonstrated a decrease in
      immobility-determined sleep time and an increase in immobility-determined sleep
      fragmentation. Secondly, Grm2/3-/- mice showed heightened sensitivity to the
      circadian effects of light, manifested as increased period lengthening in
      constant light, and greater phase delays in response to nocturnal light pulses.
      Greater light-induced phase delays were also exhibited by wildtype C57Bl/6J mice
      following administration of the mGlu2/3 negative allosteric modulator RO4432717.
      These results confirm the involvement of group II metabotropic glutamate
      receptors in photic entrainment and sleep regulation pathways. Finally, the
      diurnal wheel-running rhythms of Grm2/3-/- mice were perturbed under a standard
      light/dark cycle, but their diurnal rest-activity rhythms were unaltered in cages
      lacking running wheels, as determined with passive infrared motion detectors.
      Hence, when assessing the diurnal rest-activity rhythms of mice, the choice of
      assay can have a major bearing on the results obtained. 

PMID- 25950517
TI  - Patient and disease characteristics associated with activation for self
      management in patients with diabetes, chronic obstructive pulmonary disease,
      chronic heart failure and chronic renal disease: a cross-sectional survey study.
AB  - A substantial proportion of chronic disease patients do not respond to self
      management interventions, which suggests that one size interventions do not fit
      all, demanding more tailored interventions. To compose more individualized
      strategies, we aim to increase our understanding of characteristics associated
      with patient activation for self-management and to evaluate whether these are
      disease-transcending. A cross-sectional survey study was conducted in primary and
      secondary care in patients with type-2 Diabetes Mellitus (DM-II), Chronic
      Obstructive Pulmonary Disease (COPD), Chronic Heart Failure (CHF) and Chronic
      Renal Disease (CRD). Using multiple linear regression analysis, we analyzed
      associations between self-management activation (13-item Patient Activation
      Measure; PAM-13) and a wide range of socio-demographic, clinical, and
      psychosocial determinants. Furthermore, we assessed whether the associations
      between the determinants and the PAM were disease-transcending by testing whether
      disease was an effect modifier. In addition, we identified determinants
      associated with low activation for self-management using logistic regression
      analysis. We included 1154 patients (53% response rate); 422 DM-II patients, 290
      COPD patients, 223 HF patients and 219 CRD patients. Mean age was 69.6+/-10.9.
      Multiple linear regression analysis revealed 9 explanatory determinants of
      activation for self-management: age, BMI, educational level, financial distress,
      physical health status, depression, illness perception, social support and
      underlying disease, explaining a variance of 16.3%. All associations, except for
      social support, were disease transcending. This study explored factors associated
      with varying levels of activation for self-management. These results are a first
      step in supporting clinicians and researchers to identify subpopulations of
      chronic disease patients less likely to be engaged in self-management. Increased
      scientific efforts are needed to explain the greater part of the factors that
      contribute to the complex nature of patient activation for self-management. 

PMID- 25950518
TI  - Msx1CreERT2 knock-In allele: A useful tool to target embryonic and adult cardiac
      valves.
AB  - Heart valve development begins with the endothelial-to-mesenchymal transition
      (EMT) of endocardial cells. Although lineage studies have demonstrated
      contributions from cardiac neural crest and epicardium to semilunar and
      atrioventricular (AV) valve formation, respectively, most valve mesenchyme
      derives from the endocardial EMT. Specific Cre mouse lines for fate-mapping
      analyses of valve endocardial cells are limited. Msx1 displayed expression in AV
      canal endocardium and cushion mesenchyme between E9.5 and E11.5, when EMT is
      underway. Additionally, previous studies have demonstrated that deletion of Msx1
      and its paralog Msx2 results in hypoplastic AV cushions and impaired endocardial
      signaling. A knock-in tamoxifen-inducible Cre line was recently generated
      (Msx1CreERT2) and characterized during embryonic development and after birth, and
      was shown to recapitulate the endogenous Msx1 expression pattern. Here, we
      further analyze this knock-in allele and track the Msx1-expressing cells and
      their descendants during cardiac development with a particular focus on their
      contribution to the valves and their precursors. Thus, Msx1CreERT2 mice represent
      a useful model for lineage tracing and conditional gene manipulation of
      endocardial and mesenchymal cushion cells essential to understand mechanisms of
      valve development and remodeling.

PMID- 25950521
TI  - Geometry of anterior open bite correction.
AB  - Correction of anterior open bite is a frequently encountered and challenging
      problem for the craniomaxillofacial surgeon and orthodontist. Accurate clinical
      evaluation, including cephalometric assessment, is paramount for establishing the
      diagnosis and appropriate treatment plan. The purposes of this technical note
      were to discuss the basic geometric principles involved in the surgical
      correction of skeletal anterior open bites and to offer a simple mathematical
      model for predicting the amount of posterior maxillary impaction with concomitant
      mandibular rotation required to establish an adequate overbite. Using standard
      geometric principles, a mathematical model was created to demonstrate the
      relationship between the magnitude of the open bite and the magnitude of the
      rotational movements required for correction. This model was then validated using
      a clinical case. In summary, the amount of open bite closure for a given amount
      of posterior maxillary impaction depends on anatomic variables, which can be
      obtained from a lateral cephalogram. The clinical implication of this
      relationship is as follows: patients with small mandibles and steep mandibular
      occlusal planes will require greater amounts of posterior impaction. 

PMID- 25950519
TI  - Mutation of androgen receptor N-terminal phosphorylation site Tyr-267 leads to
      inhibition of nuclear translocation and DNA binding.
AB  - Reactivation of androgen receptor (AR) may drive recurrent prostate cancer in
      castrate patients. Ack1 tyrosine kinase is overexpressed in prostate cancer and
      promotes castrate resistant xenograft tumor growth and enhances androgen target
      gene expression and AR recruitment to enhancers. Ack1 phosphorylates AR at Tyr
      267 and possibly Tyr-363, both in the N-terminal transactivation domain. In this
      study, the role of these phosphorylation sites was investigated by characterizing
      the phosphorylation site mutants in the context of full length and truncated AR
      lacking the ligand-binding domain. Y267F and Y363F mutants showed decreased
      transactivation of reporters. Expression of wild type full length and truncated
      AR in LNCaP cells increased cell proliferation in androgen-depleted conditions
      and increased colony formation. However, the Y267F mutant of full length and
      truncated AR was defective in stimulating cell proliferation. The Y363F mutant
      was less severely affected than the Y267F mutant. The full length AR Y267F mutant
      was defective in nuclear translocation induced by androgen or Ack1 kinase. The
      truncated AR was constitutively localized to the nucleus. Chromatin
      immunoprecipitation analysis showed that it was recruited to the target enhancers
      without androgen. The truncated Y267F AR mutant did not exhibit constitutive
      nuclear localization and androgen enhancer binding activity. These results
      support the concept that phosphorylation of Tyr-267, and to a lesser extent Tyr
      363, is required for AR nuclear translocation and recruitment and DNA binding and
      provide a rationale for development of novel approaches to inhibit AR activity. 

PMID- 25950522
TI  - Infratemporal fossa cellulitis caused by a remnant iatrogenic foreign body after
      a bimaxillary operation.
AB  - Infratemporal fossa cellulitis is rare and mostly occurs because of sinusitis and
      dental procedures. Furthermore, cellulitis caused by iatrogenic foreign bodies is
      very rare. A 28-year-old woman who had previously undergone cosmetic bimaxillary
      operation visited our hospital complaining of left facial swelling, oppressive
      pain, and nasal obstruction since 2 years. She had been attending another clinic,
      but despite having additional procedures and taking medications, her symptoms
      persisted. A subsequent operation was performed, during which we found a remnant
      surgical gauze from the previous operation, which was decomposed and trapped
      around the necrotic soft tissue and had eroded the bony structure around the
      pterygoid fossa. The material was successfully removed by endoscopic surgery, and
      the necrotic tissue was debrided. After the operation, all symptoms disappeared,
      and the patient was discharged without sequelae. During any procedure, surgeons
      must meticulously check for remnant material. Additionally, physicians must
      carefully note patient history and perform a physical examination, even in
      patients without serious symptoms. We report a case of advanced infratemporal
      fossa cellulitis due to remnant gauze material during a previous operation that
      was undetected.

PMID- 25950520
TI  - CXCR2 inhibition suppresses acute and chronic pancreatic inflammation.
AB  - Pancreatitis is a significant clinical problem and the lack of effective
      therapeutic options means that treatment is often palliative rather than
      curative. A deeper understanding of the pathogenesis of both acute and chronic
      pancreatitis is necessary to develop new therapies. Pathological changes in
      pancreatitis are dependent on innate immune cell recruitment to the site of
      initial tissue damage, and on the coordination of downstream inflammatory
      pathways. The chemokine receptor CXCR2 drives neutrophil recruitment during
      inflammation, and to investigate its role in pancreatic inflammation, we induced
      acute and chronic pancreatitis in wild-type and Cxcr2(-/-) mice. Strikingly,
      Cxcr2(-/-) mice were strongly protected from tissue damage in models of acute
      pancreatitis, and this could be recapitulated by neutrophil depletion or by the
      specific deletion of Cxcr2 from myeloid cells. The pancreata of Cxcr2(-/-) mice
      were also substantially protected from damage during chronic pancreatitis.
      Neutrophil depletion was less effective in this model, suggesting that CXCR2 on
      non-neutrophils contributes to the development of chronic pancreatitis.
      Importantly, pharmacological inhibition of CXCR2 in wild-type mice replicated the
      protection seen in Cxcr2(-/-) mice in acute and chronic models of pancreatitis.
      Moreover, acute pancreatic inflammation was reversible by inhibition of CXCR2.
      Thus, CXCR2 is critically involved in the development of acute and chronic
      pancreatitis in mice, and its inhibition or loss protects against pancreatic
      damage. CXCR2 may therefore be a viable therapeutic target in the treatment of
      pancreatitis.

PMID- 25950524
TI  - Epithelioid sarcoma on the face in an elderly patient.

PMID- 25950523
TI  - Primary cutis verticis gyrata.

PMID- 25950525
TI  - Repair of the complicated orocutaneous fistula using atelocollagen sponge.

PMID- 25950526
TI  - Posttraumatic fibrolipoma of the malar area.

PMID- 25950528
TI  - Complications after mandibular third molar surgery: a case of bulky peripheral
      osteoma.

PMID- 25950527
TI  - Late-onset adverse reactions related to hyaluronic Acid dermal filler for
      aesthetic soft tissue augmentation.
AB  - Hyaluronic acid (HA) fillers have been the choice material for soft tissue
      augmentation in the last decade. Although they are considered safe, there could
      be adverse reactions in the subsequent months or years to the treatment. However,
      these reactions have hardly ever been reported in the literature. This article
      considers 2 cases of delayed adverse reactions related to HA dermal filler for
      soft tissue augmentation with oral manifestation. It should be, before all,
      emphasized that HA filler is a safe and well-recognized treatment for soft tissue
      augmentation, despite the fact that delayed adverse effects may later occur after
      treatment, and clinicians should be aware of it when establishing a definitive
      oral diagnosis. 

PMID- 25950529
TI  - Histologic Study of the Articular Eminence in Wilkes IV Temporomandibular Joint
      Disorder Patients.

PMID- 25950530
TI  - Adverse events during the removal of impacted lower third molars.

PMID- 25950532
TI  - Emerging biologics in orthopedics.

PMID- 25950531
TI  - Evaluation of iTRAQ and SWATH-MS for the Quantification of Proteins Associated
      with Insulin Resistance in Human Duodenal Biopsy Samples.
AB  - Insulin resistance (IR) is associated with increased production of triglyceride
      rich lipoproteins of intestinal origin. In order to assess whether insulin
      resistance affects the proteins involved in lipid metabolism, we used two mass
      spectrometry based quantitative proteomics techniques to compare the intestinal
      proteome of 14 IR patients to that of 15 insulin sensitive (IS) control patients
      matched for age and waist circumference. A total of 3886 proteins were identified
      by the iTRAQ (Isobaric Tags for Relative and Absolute Quantitation) mass
      spectrometry approach and 2290 by the SWATH-MS strategy (Serial Window
      Acquisition of Theoretical Spectra). Using these two methods, 208 common proteins
      were identified with a confidence corresponding to FDR < 1%, and quantified with
      p-value < 0.05. The quantification of those 208 proteins has a Pearson
      correlation coefficient (r2) of 0.728 across the two techniques. Gene Ontology
      analyses of the differentially expressed proteins revealed that annotations
      related to lipid metabolic process and oxidation reduction process are overly
      represented in the set of under-expressed proteins in IR subjects. Furthermore,
      both methods quantified proteins of relevance to IR. These data also showed that
      SWATH-MS is a promising and compelling alternative to iTRAQ for protein
      quantitation of complex mixtures. 

PMID- 25950533
TI  - Retrograde reamer/irrigator/aspirator technique for autologous bone graft
      harvesting with the patient in the prone position.
AB  - In recent years, the Reamer/Irrigator/Aspirator (RIA) system (Synthes, West
      Chester, Pennsylvania) has emerged as an extremely effective alternative in
      harvesting large volumes of autologous bone graft through reaming of the femoral
      intramedullary canal. The technique has been described in the literature as using
      an antegrade approach to the femur with the patient in the supine or prone
      position. It has also been described as a retrograde approach in the supine
      position. In this article, we describe a new technique-a retrograde femoral
      approach with the patient in the prone position. This technique allows for more
      efficient preparation by eliminating the need to reposition, reprepare, and
      redrape the extremity, thus decreasing operative time and risk of infection.
      Although we present this technique for use in ankle and hindfoot arthrodesis, we
      think it can be valuable in any prone-position procedure, including spine
      surgery. 

PMID- 25950534
TI  - Percutaneous fixation of hypertrophic nonunion of the inferior pubic ramus: a
      report of two cases and surgical technique.
AB  - Symptomatic hypertrophic nonunions of the inferior pubic ramus are amenable to
      percutaneous screw fixation in patients with suitable osseous anatomy.
      Preoperative planning, knowledge of bony and surrounding soft-tissue anatomy, and
      understanding of intraoperative pelvic fluoroscopy are required for proper screw
      fixation in the medullary canal of the inferior pubic ramus. In this article, we
      report 2 cases of adults with symptomatic hypertrophic nonunions of the superior
      and inferior pubic ramus, treated successfully with percutaneous medullary screw
      fixation. Percutaneous screw fixation can be used to successfully treat
      symptomatic hypertrophic nonunion of the inferior ramus and avoid the potential
      morbidity of a more extensive open surgical procedure. 

PMID- 25950535
TI  - Enhancement of acute tendon repair using chitosan matrix.
AB  - Structural failure of rotator cuff repairs has been attributed to multiple
      factors, including poor repair tissue quality and poor tendon-bone integration.
      Chitosan gel has been shown to facilitate scarless healing of soft tissues. In
      the study reported here, we hypothesized that use of a chitosan gel would improve
      the morphologic appearance of acute rotator cuff repair in a rat model after 12
      weeks. Forty Wistar rats were used. In each case, bilateral tenotomy of the
      supraspinatus tendon was performed, followed by acute repair with sutures. The
      left shoulder served as a suture-only control, and the right shoulder was
      augmented with a chitosan gel applied between the ends of the tendon. Histologic
      analyses were performed to determine the functional and anatomical
      characteristics of the repair immediately after the operation and 3 days and 1,
      2, 4, 6, 8, and 12 weeks after surgery. In the gel-augmented specimens, number of
      fibroblasts and amount of repair tissue were increased. Compared with the
      controls, these specimens showed minimal evidence of monocytic infiltration or
      inflammatory response around the matrix. Structural properties of the augmented
      shoulder, including pennation angles and fatty atrophy, were significantly
      improved. These study results showed that use of a chitosan matrix can enhance
      biological repair of rotator cuff tendons in a rat model. 

PMID- 25950536
TI  - Long-term outcomes of allograft reconstruction of the anterior cruciate ligament.
AB  - Recent studies have found higher rates of failed reconstruction of the anterior
      cruciate ligament (ACL) with use of allograft when compared with autograft
      reconstruction. To evaluate the long-term outcomes of allograft ACL
      reconstruction, we retrospectively reviewed the cases of all patients who
      underwent allograft (n=99) or autograft (n=24) ACL reconstruction by 2 senior
      surgeons at a single institution over an 8-year period. Seventeen (17%) of the 99
      allograft reconstructions required additional surgery. Reoperation and revision
      ACL reconstruction rates (30.8% and 20.5%, respectively) were much higher for
      patients 25 years of age or younger than for patients older than 25 years. In our
      cohort of NCAA (National Collegiate Athletic Association) Division I athletes,
      the revision ACL reconstruction rate was 62% for allograft ACL reconstruction and
      0% for autograft reconstruction. Our study found that reoperation and revision
      rates for irradiated soft-tissue allograft ACL reconstruction were higher than
      generally quoted for autograft reconstruction. Given the extremely high graft
      failure rates in patients younger than 25 years, we recommend against routine use
      of irradiated soft-tissue allograft for ACL reconstruction in younger patients.

PMID- 25950537
TI  - Arthroscopic posterior-inferior capsular release in the treatment of overhead
      athletes.
AB  - In this article, we present our technique for arthroscopic posterior-inferior
      capsular release and report the results of applying this technique in a
      population of athletes with symptomatic glenohumeral internal rotation deficit
      (GIRD) that was unresponsive to nonoperative treatment and was preventing them
      from returning to sport. Fifteen overhead athletes met the inclusion criteria.
      Two were lost to follow-up. Of the 13 remaining, 6 underwent isolated posterior
      inferior capsular releases, and 7 had concomitant procedures. Before and after
      surgery, patients completed an activity questionnaire, which included the
      American Shoulder and Elbow Surgeons (ASES) Standardized Shoulder Assessment
      Form. Passive internal rotation in the scapular plane was measured with a bubble
      goniometer. Mean age was 21 years (range, 16-33 years). Mean follow-up was 31.1
      months (range, 24-59 months). Mean ASES score improved significantly (P<.01) from
      before surgery (71.5) to after surgery (86.9). Mean GIRD improved from 43.1
      degrees  to 9.7 degrees  (P<.05). Three athletes (23%) did not return to their
      preoperative level of play; the other 10 (77%) returned to their same level of
      play or a higher level. Selective arthroscopic posterior-inferior capsular
      release may be a reasonable solution for overhead athletes with symptomatic GIRD
      unresponsive to conservative management.

PMID- 25950538
TI  - Operative intervention for geriatric hip fracture: does type of surgery affect
      hospital length of stay?
AB  - Hip fractures are the most costly fall-related fractures. Differences in hospital
      length of stay (LOS) based on type of surgery could have major financial
      implications in a potential bundled payment system in which all hip fractures are
      reimbursed a standard amount. We conducted a study to analyze differences in
      hospital LOS and costs for total hip arthroplasty (THA), hemiarthroplasty (HA),
      cephalomedullary nailing, open reduction and internal fixation (ORIF), and closed
      reduction and percutaneous pinning (CRPP). Through retrospective chart review,
      615 patients over age 60 years across a 9-year period at an urban level I trauma
      center were identified. Mean LOS and costs for hip fracture repair were 6.91 days
      and $30,011.25, respectively. HA/THA was associated with the longest mean LOS
      (7.43 days) and highest costs ($33,657.90). After several patient factors were
      adjusted for, ORIF was associated with 0.84 fewer in-patient days and $3805.20
      less in hospitalization costs compared with HA/THA (P=.042). CRPP was associated
      with 1.63 fewer days and $7383.90 less in costs than HA/THA (P=.0076). Our
      results provide insight into the financial implications of hip fracture fixation
      and identify targets for quality improvement initiatives to improve efficiency of
      resource utilization.

PMID- 25950539
TI  - Total hip arthroplasty after contralateral hip disarticulation: a challenging
      "simple primary".
AB  - Patients with lower limb amputation have a high incidence of hip and knee
      osteoarthritis in both the residual limb and the contralateral limb. Hip
      disarticulation is a radical surgery usually performed in younger patients after
      malignancy or trauma. Compliance is poor with existing prostheses, resulting in
      increased dependency on and use of the remaining sound limb. We describe a case
      of a crutch-walking 51-year-old woman who presented with severe left hip
      arthritis 25 years after a right hip disarticulation, and was treated with total
      hip arthroplasty. Total hip arthroplasty without a contralateral hip joint is
      challenging. We discuss the complex technical considerations associated with the
      patient's arthroplasty, in particular the selection of prostheses and bearing
      surfaces, and the preoperative and intraoperative assessment of limb length and
      offset. 

PMID- 25950540
TI  - 21st-Century Patient Collections: Implement a Point-of-Service Collections
      Program Now.

PMID- 25950541
TI  - Polydactyly of the hand.
AB  - Polydactyly is considered either the most or second most (after syndactyly)
      common congenital hand abnormality. Polydactyly is not simply a duplication; the
      anatomy is abnormal with hypoplastic structures, abnormally contoured joints, and
      anomalous tendon and ligament insertions. There are many ways to classify
      polydactyly, and surgical options range from simple excision to complicated bone,
      ligament, and tendon realignments. The prevalence of polydactyly makes it
      important for orthopedic surgeons to understand the basic tenets of the
      abnormality. 

PMID- 25950542
TI  - Patients' perceptions of the costs of total hip and knee arthroplasty.
AB  - With medical economics in the national sociopolitical spotlight, we conducted a
      study to assess patients' understanding of the cost of 2 common orthopedic
      procedures: total hip and knee arthroplasty (THA, TKA). We surveyed 284
      consecutive THA or TKA patients, at their first postoperative visit, regarding
      their understanding of reimbursement and cost. On average, patients estimated
      surgeon reimbursement at $12,014. They estimated that the hospital was reimbursed
      $28,392 for their perioperative care and that it cost the hospital $24,389 to
      provide it. The cost of the implant used was estimated at $6447. There is wide
      variation in patients' estimates and understanding of health care costs. However,
      patients substantially overestimate reimbursement to the surgeon both in
      isolation and as a proportion of the total cost of the surgical procedure. 

PMID- 25950543
TI  - Risk factors for in-hospital myocardial infarction after shoulder arthroplasty.
AB  - As cardiovascular complications are associated with significant morbidity and
      mortality in patients who have arthroplasty, it is important to analyze risk
      factors for perioperative cardiac morbidity after shoulder arthroplasty. Using
      the Nationwide Inpatient Sample, we stratified patients who underwent shoulder
      arthroplasty into those who had an acute myocardial infarction after arthroplasty
      and a larger cohort of patients who did not. The top 4 predictors for acute
      myocardial infarction after shoulder arthroplasty were congestive heart failure,
      angina pectoris, complicated diabetes mellitus, and male sex. Other pertinent
      factors were older age, Caucasian ethnicity, and primary diagnosis of proximal
      humerus fracture. It is prudent for surgeons and patients to understand the
      degree to which perioperative cardiac morbidity affects surgical recovery. 

PMID- 25950544
TI  - Assessment of scapular morphology and surgical technique as predictors of
      notching in reverse shoulder arthroplasty.
AB  - There has been increased focus on understanding risk factors for scapular
      notching in reverse shoulder arthroplasty (RSA). We conducted a study to evaluate
      the scapular notching index and other factors associated with the occurrence of
      scapular notching. Ninety-one patients treated with primary RSA were followed for
      a minimum of 24 months. Patients' radiographic assessments were grouped by Nerot
      grade of scapular notching (group 1, grades 0 and 1; group 2, grades 2, 3, 4).
      Group mean differences were compared for preoperative scapular neck angle (SNA),
      prosthesis-scapular neck angle (PSNA), peg glenoid rim distance (PGRD), notching
      index, and clinical outcomes. There was no significant difference in mean (SD)
      notching index between group 1, 31.8 (4.4), and group 2, 33.1 (7.3), and there
      were no significant differences in SNA (102.8 degrees  vs 105.4 degrees ; P=.3),
      PSNA (125.8 degrees  vs 125.4 degrees ; P=.82), PGRD (15.4 vs 16.8 mm; P=.47), or
      clinical outcomes between the groups. Our results suggest that Grammont-style
      prostheses have a higher rate of notching regardless of optimal PGRD and
      variations in PSNA. Perhaps with certain scapular morphology, prosthetic design
      may be a more significant contributor to notching.

PMID- 25950545
TI  - Recurrent patellar tendon rupture in a patient after intramedullary nailing of
      the tibia: reconstruction using an Achilles tendon allograft.
AB  - Various complications after intramedullary (IM) nailing of the tibia have been
      reported, the most common of which are anterior knee pain and symptoms similar to
      patella tendonitis. Complete rupture of the patellar tendon after IM nailing of
      the tibia has been reported on 2 occasions, in conjunction with predisposing
      patient factors, such as systemic disease or a proud tibial nail. Patellar tendon
      ruptures are disabling injuries that can be technically difficult to repair
      because of the poor quality of remaining tendon tissue, quadriceps muscle atrophy
      and/or contracture, and scar-tissue formation. Many methods have described the
      surgical reconstruction of the knee extensor mechanism, which is most commonly
      performed after total knee arthroplasty. We report the successful surgical and
      clinical outcome of patellar tendon reconstruction using an Achilles tendon
      allograft in a patient subject to late and recurrent ruptures after IM nailing of
      the tibia through a mid-patellar tendon-splitting approach. Seven months after
      tendon reconstruction, the patient exhibited full knee flexion, an extension lag
      of 10o, 4/5 quadriceps strength, and return to her baseline ambulatory status. 

PMID- 25950546
TI  - Popliteal artery pseudoaneurysm: an unusual complication of tibial traction.
AB  - Traction pins are an essential tool in the orthopedic surgeon's armamentarium.
      Historically a definitive treatment for some fractures, they are mainly used as a
      temporizing measure today. Despite their frequent use and relative simplicity,
      traction pins can have complications, many of which can be subtle and easily
      overlooked. Here we report on an unusual complication that was difficult to
      diagnose but caused significant morbidity before being diagnosed and treated.
      Pseudoaneurysms can cause a range of symptoms and usually present as a painful,
      tender, pulsatile mass, but in this instance the popliteal artery pseudoaneurysm
      presented as chronic, painful lower extremity swelling. With diagnosis and
      treatment, the patient's symptoms resolved. We discuss the complications
      associated with traction-pin placement. 

PMID- 25950547
TI  - Arthroscopic treatment of tibial spine malunion with resorbable screws.
AB  - Anterior tibial spine fractures are rare and were thought to occur mainly in
      children; however, recent literature indicates that the incidence in adults is
      much greater than previously thought. Because the tibial spine is an attachment
      point for the anterior cruciate ligament (ACL), an avulsion may produce ACL
      laxity, predisposing to further issues. We report the case of an 11-year-old boy
      with a tibial spine fracture that failed conservative management. He developed a
      malunion with impingement anteriorly of the tibial spine on the notch and
      residual instability of the ACL. In this report, we present a novel approach for
      arthroscopic reduction of a tibial spine fracture using 8 resorbable poly-L
      lactic/polyglycolic acid nails. 

PMID- 25950548
TI  - Orthopedic residents: what are we worth?

PMID- 25950550
TI  - Generating skeletal diversity from the C19 -diterpenoid alkaloid deltaline: a
      ring-distortion approach.
AB  - The development of new drugs calls for large collections of diverse molecules
      with considerable complexity. Ring distortion of natural products provides an
      efficient and facile approach to access new architectures with intriguing
      biological activities, by harnessing their inherent complexity. In this study,
      such a strategy has been explored on an abundant C19 -diterpenoid alkaloid,
      deltaline, enabling the synthesis of 32 new derivatives bearing a broad spectrum
      of unique scaffolds. Extensive spectroscopic studies including X-ray
      crystallographic analyses strongly supported the structures of the obtained novel
      skeletons, which present comparable opportunities with the great contributions
      made by nature for discovery of new lead compounds. 

PMID- 25950549
TI  - ATOH1 Can Regulate the Tumorigenicity of Gastric Cancer Cells by Inducing the
      Differentiation of Cancer Stem Cells.
AB  - Cancer stem cells (CSCs) have been shown to mediate tumorigenicity, chemo
      resistance, radio-resistance and metastasis, which suggest they be considered
      therapeutic targets. Because their differentiated daughter cells are no longer
      tumorigenic, to induce the differentiation of CSCs can be one of strategies which
      can eradicate CSCs. Here we show that ATOH1 can induce the differentiation of
      gastric cancer stem cells (GCSCs). Real time PCR and western blot analysis showed
      that ATOH1 was induced during the differentiation of GCSCs. Furthermore, the
      lentivirus-induced overexpression of ATOH1 in GCSCs and in gastric cancer cell
      lines significantly induced differentiation, reduced proliferation and sphere
      formation, and reduced in vivo tumor formation in the subcutaneous injection and
      liver metastasis xenograft models. These results suggest ATOH1 be considered for
      the development of a differentiation therapy for gastric cancer. 

PMID- 25950552
TI  - Papanicolaou smears of atypical glandular cells of undetermined significance:
      histological correlations and suggestions for management.
AB  - OBJECTIVE: We sought to correlate cervical and endometrial neoplasias with
      Papanicolaou (Pap) smears of atypical glandular cells of undetermined
      significance (AGUS) and to suggest management. MATERIALS AND METHODS: One hundred
      seventy-one patients with AGUS Pap smears were followed prospectively with
      colposcopy, biopsies, endocervical curettage, and endometrial biopsies. RESULTS:
      One hundred twelve patients (65%) with AGUS Pap smears favoring reactive changes
      were found to harbor 13 preinvasive and invasive cervical squamous neoplasias and
      1 ovarian sarcoma (total, 12.5% of patients with smears). Fifty-nine patients
      (35%) with AGUS Pap smears favoring neoplastic changes harbored 25 preinvasive
      and invasive squamous and glandular cervical and endometrial neoplasias (42.3%).
      CONCLUSION: In the presence of an AGUS Pap smear favoring reactive changes,
      colposcopy, biopsies, and endocervical curettage should be performed. Endometrial
      biopsy should be added when AGUS Pap smear favors neoplasia.

PMID- 25950551
TI  - Specific default mode subnetworks support mentalizing as revealed through
      opposing network recruitment by social and semantic FMRI tasks.
AB  - The ability to attribute mental states to others, or "mentalizing," is posited to
      involve specific subnetworks within the overall default mode network (DMN), but
      this question needs clarification. To determine which default mode (DM)
      subnetworks are engaged by mentalizing processes, we assessed task-related
      recruitment of DM subnetworks. Spatial independent component analysis (sICA)
      applied to fMRI data using relatively high-order model (75 components). Healthy
      participants (n = 53, ages 17-60) performed two fMRI tasks: an interactive game
      involving mentalizing (Domino), a semantic memory task (SORT), and a resting
      state fMRI scan. sICA of the two tasks split the DMN into 10 subnetworks located
      in three core regions: medial prefrontal cortex (mPFC; five subnetworks),
      posterior cingulate/precuneus (PCC/PrC; three subnetworks), and bilateral
      temporoparietal junction (TPJ). Mentalizing events increased recruitment in five
      of 10 DM subnetworks, located in all three core DMN regions. In addition, three
      of these five DM subnetworks, one dmPFC subnetwork, one PCC/PrC subnetwork, and
      the right TPJ subnetwork, showed reduced recruitment by semantic memory task
      events. The opposing modulation by the two tasks suggests that these three DM
      subnetworks are specifically engaged in mentalizing. Our findings, therefore,
      suggest the unique involvement of mentalizing processes in only three of 10 DM
      subnetworks, and support the importance of the dmPFC, PCC/PrC, and right TPJ in
      mentalizing as described in prior studies.

PMID- 25950553
TI  - Endocervical metaplasias and their association with glandular and squamous
      abnormalities.
AB  - OBJECTIVE: The presence of endocervical metaplasias and their association with
      cervical squamous and glandular neoplasias were studied. MATERIALS AND METHODS:
      Cervical specimens were examined microscopically to identify the presence of
      glandular metaplasias. The type of cervical neoplastic abnormality, when present,
      also was recorded. Statistical analyses of the microscopical findings included
      frequency observation counts and contingency analysis (Fisher's exact test).
      RESULTS: One hundred eighty-seven cervices were examined. Diagnoses included
      adenocarcinoma (8), adenocarcinoma in situ (14), glandular dysplasia (4),
      squamous carcinoma (2) and cervical intraepithelial neoplasia (78); 4 cervices
      had combined squamous and glandular abnormalities. Eighty-seven had no evidence
      of cervical neoplasias. The glandular metaplasias were tubal (79 ciliated cell, 3
      eosinophilic cell) and intestinal (22); 14 cases had combined tubal and
      intestinal metaplastic change. Ninety-seven cervices had no evidence of glandular
      metaplasia. Intestinal metaplasia was intimately associated (p = .0002) with
      neoplastic changes, particularly glandular abnormalities. Ciliated cell
      metaplasia also was associated with glandular or squamous abnormalities (p <
      .04), but more than one-third of specimens with this metaplasia had no associated
      abnormality. CONCLUSIONS: A high degree of association exists between cervical
      intestinal glandular metaplasia and cervical glandular and squamous neoplasias.
      Patients with this metaplastic change should be followed up closely if no
      associated lesion is found initially.

PMID- 25950554
TI  - Colposcopy of adenocarcinoma in situ and adenocarcinoma of the uterine cervix:
      differentiation from other cervical lesions.
AB  - Colposcopic features of cervical adenocarcinoma in situ (AIS) and adenocarcinoma
      exist, and colposcopists can learn to recognize them. This ability will increase
      the colposcopic discovery rate for these lesions and can lead to appropriate
      management in early stages. An excisional biopsy with negative margins is
      required to differentiate between in situ and invasive disease. The general
      categories of revealing features are surface patterns and blood vessels. Surface
      patterns indicative of AIS and adenocarcinoma are (1) lesions overlying columnar
      epithelium not contiguous with the squamocolumnar border; (2) lesions with large
      "gland"/cleft openings; (3) papillary lesions; (4) lesion exhibiting epithelial
      budding; and (5) variegated red and white lesions. Blood vessels indicative of
      AIS or adenocarcinoma are (1) waste-thread-like vessels; (2) tendril-like
      vessels; (3) rootlike vessels; (4) character-writing-like vessels; and (5) single
      and multiple dotlike formations in tips of papillary excrescences. Some of these
      characteristics also are apparent when other disease processes are present, but
      an observant colposcopist can differentiate lesions using inclusionary and
      exclusionary criteria. 

PMID- 25950555
TI  - Reproducibility of the histopathological classification of vulvar squamous
      carcinoma and intraepithelial neoplasia.
AB  - Invasive vulvar carcinoma has been shown to be etiologically heterogeneous on the
      basis of pathological, virological, and epidemiological criteria. Human
      papillomavirus-related invasive vulvar carcinoma has basaloid or warty morphology
      and has adjacent basaloid or warty intraepithelial neoplasia. Invasive carcinoma
      unrelated to human papillomavirus is a keratinizing squamous carcinoma that may
      have adjacent squamous hyperplasia. We provided to 3 pathologists for their
      review and pathological diagnoses stained tissue sections from 95 patients with
      vulvar carcinoma. The reproducibility for grading individual categories of
      intraepithelial lesions was only fair (kappa values of 0.31-0.43). The
      reproducibility was better (moderate to good; kappa values of 0.58-0.59) for
      grading individual categories of invasive carcinomas. The agreements improved
      when the basaloid and warty categories were combined. Good agreement was achieved
      (kappa values of 0.55-0.79) in distinguishing human papillomavirus-related
      lesions from those unrelated to human papillomavirus; all three reviewers agreed
      on this classification for 67% of the cases. The intrareviewer agreement was of
      the same order as interreviewer agreement. Difficulties in differentiating
      between some lesions (e.g., a warty carcinoma with little atypia from a well- to
      moderately differentiated keratinizing squamous carcinoma) and concurrent
      occurrence of human papillomavirus-related lesions and those lesions unrelated to
      human papillomavirus in a patient may account for some of the discrepancies in
      the histopathological diagnoses of vulvar carcinoma. 

PMID- 25950556
TI  - A prospective study of biopsy-confirmed cervical intraepithelial neoplasia grade
      1: colposcopic, cytological, and virological risk factors for progression.
AB  - OBJECTIVES: The objective of this prospective study of histologically confirmed
      cervical intraepithelial neoplasia (CIN) (including equivocal CIN1) was to
      determine risk factors for progression to histologically confirmed CIN3,
      particularly human papillomavirus (HPV) types and cofactors. We postulated that
      HPV DNA positivity would be a strong, prospective risk factor for progression.
      MATERIALS AND METHODS: Possible participants were referred with an abnormal
      cytological diagnosis of CIN1 or lower-grade disease or external genital warts.
      Women with histologically confirmed CIN1 (including koilocytotic atypia) or
      equivocal CIN1 were eligible for follow-up. Of these, 163 women were assessed
      every 3 months (if a lesion were present) or every 6 months (if a lesion
      regressed colposcopically during the course of the study), for up to 52 months.
      Progression was defined histologically, whereas persistence and regression were
      defined by combined cytological, colposcopic, and histological assessments.
      Subjects who progressed to a biopsy-confirmed CIN3 or who developed a lesion that
      was clinically unsafe to follow up (i.e., because of movement into the
      endocervical canal), were removed from the study and were treated. RESULTS: A
      total of 237 patients were evaluated as possible participants. The 74 exclusions
      at enrollment included 33 patients who had an entry diagnosis of CIN2 to CIN3 or
      who had lesions that were otherwise already unsafe to follow up, 39 who did not
      have a lesion on colposcopically directed biopsy, and 2 who were immediately
      noncompliant. Among the remaining 163 participants, the overall progression rate
      to histologically confirmed CIN3 was 8%, the persistence rate was 49%, and the
      regression rate was 43%. All progressions occurred among women who were HPV DNA
      positive and had colposcopically immature abnormal transformation zones.

PMID- 25950557
TI  - Ki-67 Expression in a Cervical Cancer Organotypic Model Correlates with Growth
      and EGF-R Expression.
AB  - OBJECTIVE: The study objective was to measure the effects of retinoid treatment
      on Ki-67 expression in a cervical carcinoma organotypic culture model and to
      determine whether a correlation exists between retinoid effects on Ki-67
      expression and effects on growth and epidermal growth factor receptor (EGF-R)
      expression. METHODS: Organotypic cultures of the cervical carcinoma cell line
      were treated for 7 days with all-trans retinoic acid, 9-cis retinoic acid, or
      control solvent. Cultures were fixed and embedded in paraffin, and sections were
      stained with Ki-67 antibodies. Ki-67 expression was determined by light
      microscopy. RESULTS: Ki-67 expression was inhibited 25% in the organotypic
      culture treated with 9-cis retinoic acid and 32% in the culture treated with all
      frans retinoic acid. Previous data demonstrated a 45% and 44% inhibition of EGF-R
      expression and a 49% and 63% inhibition of growth, respectively. DISCUSSION: The
      inhibition of Ki-67 expression by retinoids correlates with inhibition of EGF-R
      expression and growth as determined by a Pearson correlation (R = 0.88).
      Inhibition of Ki-67 and EGF-R demonstrates quantifiable effects of retinoids at
      both the membrane receptor and nuclear protein levels in our organotypic culture
      model.

PMID- 25950558
TI  - The efficacy of loop electrosurgical excision procedure as compared to cold-knife
      cone biopsy in patients with unsatisfactory colposcopy.
AB  - OBJECTIVES: Our aim was to determine whether the loop electrosurgical excision
      procedure (LEEP) is as efficacious as cone biopsy in patients with cervical
      dysplasia and unsatisfactory colposcopy. MATERIALS AND METHODS: Fifty-four
      patients with unsatisfactory coiposcopic findings underwent a LEEP procedure for
      the treatment of their cervical dysplasia. These patients were compared to 41
      patients who had a cold-knife cone biopsy for the same indication. LEEP
      procedures were carried out to a standard ectocervical excision depth of 6 mm and
      then excised centrally to an endocervical depth of an additional 3 mm. An
      endocervical curettage was performed after the excision procedure. Patients were
      examined every 4 to 6 months after treatment with a Papanicolaou smear and
      colposcopy. The pretreatment cytology and cervical biopsies, histology of LEEP
      and cone biopsy specimens, and follow-up cytology between the two groups were
      compared by chisquare analysis. RESULTS: No statistical difference was seen in
      the pretreatment cervical smears between the LEEP and cone biopsy groups. All
      LEEP and cone biopsy specimen resection margins were negative. No difference was
      evident in the grade of cervical intraepithelial neoplasia between the LEEP and
      cone biopsy groups. Follow-up cervical smear results were similar in both groups.
      One patient required a cone biopsy for persistent disease 8 months after her LEEP
      treatment. CONCLUSIONS: LEEP appears to be as safe and effective as cone biopsy
      in patients with unsatisfactory colposcopy.

PMID- 25950559
TI  - Perspectives in cervical cancer prevention and health services management.
AB  - Preventive screening, management, and treatment of patients at risk for cervical
      cancer reduces the incidence of cervical cancer in the United States but not
      without significant costs. The costs can be measured both in dollars and in
      "opportunity costs" (access to care for one patient affecting another patient
      visit) associated with providing care to an overburdened colposcopy
      infrastructure. To provide colposcopic services, sometimes access to other needed
      care may be neglected in clinical practices that are already overburdened by high
      demand and limited access to care. Colposcopy services in the fee-for-service,
      managed-care, health maintenance organizations, and academic health service
      delivery settings are delivered not solely on the basis of quality (expertise and
      technological advances) of care. Delivery of colposcopy services should be
      balanced by economic and service-related issues as well. This study aids
      clinicians in assessing the value of interventions based on the value equation
      for health care: quality, service, and cost impact. 

PMID- 25950560
TI  - A case report of disseminated tuberculosis: an unsuspected uterine cervical mass
      in a young native american woman with new-onset seizure disorder.
AB  - Disseminated tuberculosis involving the uterine cervix and central nervous system
      is described in a 26-year-old Native American female with new-onset seizures. Her
      presenting complaint was generalized seizures with associated weight loss,
      chronic cough, global headache, and malaise. Pelvic examination revealed an
      exophytic cervical mass consistent with carcinoma. Laboratory results showed
      anemia, hypoalbuminemia, and radiodensities on chest radiography. Cultures of
      sputum and cervix were positive for Mycobacterium tuberculosis. Cervical biopsies
      revealed multiple acid-fast bacilli. Computed tomography of the head showed
      multiple tuberculomas. The patient was treated with multidrug antituberculous
      therapy for 6 months, with resolution of seizures and improvement in computed
      tomographic findings. 

PMID- 25950561
TI  - Dermatofibrosarcoma protuberans of the vulva: report of two new cases and review
      of the literature.
AB  - BACKGROUND: Dermatofibrosarcoma protuberans (DFSP), a low-grade sarcoma of dermal
      origin, rarely is found on the vulva. Only 16 cases of DFSP of the vulva have
      been described. CASES: Two patients with long histories of primary vulvar
      dermatofibrosarcoma protuberans are presented. Both required multiple excisions
      to resect the tumor completely. The patients remain without evidence of disease
      after long-term follow-up. One patient is among the youngest recorded. All
      published cases of vulvar DFSP are reviewed. CONCLUSIONS: Both our experience and
      that reported in previous cases indicate that wide local excision is required in
      the treatment of vulvar DFSP.

PMID- 25950562
TI  - Dermatofibrosarcoma protuberans of the vulva: a rare tumor presenting during
      pregnancy in a teenager.
AB  - OBJECTIVES: We report a case of a young patient with dermatofibrosarcoma
      protuberans of the vulva diagnosed during pregnancy. We also provide a review of
      the literature on this topic. MATERIALS AND METHODS: This patient's case was
      reviewed retrospectively. A current literature search was performed and findings
      were reported. RESULTS: This rare malignancy was diagnosed during pregnancy in a
      teenager. CONCLUSIONS: Dermatofibrosarcoma protuberans of the vulva, a rare
      vulvar neoplasm mostly associated with older patients and never before reported
      during pregnancy, should be considered as part of the differential diagnosis for
      any vulvar mass and cannot be excluded on the basis of the patient's age or
      pregnancy status.

PMID- 25950563
TI  - Home study course: spring 1999.
AB  - OBJECTIVE: The Home Study Course is intended for the practicing colposcopist or
      practitioner who is seeking to develop or enhance his or her colposcopic skills.
      The goal of the course is to present colposcopic cases that are unusual or
      instructive in terms of apearance, presentation, or management, or that
      demonstrate new and important knowledge in the area of colposcopy or pathology.
      Participants may benefit from reading and studying the material or from testing
      their knowledge by answering the questions. ACCME ACCREDIATION: The American
      Society for Colposcopy and Cervical Pathology (ASCCP) is accredited by the
      Accreditation Council for Continuing Medical Education (ACCME) to sponsor
      continuing medical education for physicians. The ASCCP designates this continuing
      medical education activity for 1 credit hour in Category I of the Physicians'
      Recognition Award of the American Medical Association. Credit is available for
      those who choose to apply. The Home Study Course is planned and produced in
      accordance with the ACCME's Essentials.

PMID- 25950564
TI  - American society for colposcopy and cervical pathology.

PMID- 25950565
TI  - Brachial-cephalic fistula recovered with drainage for the basilic vein: Case
      report.
AB  - Vascular access is essential for the implementation of hemodialysis (HD). The
      arteriovenous fistula (AVF) can be constructed in various locations using various
      veins. However, the quality of the veins will influence the construction site, as
      well as the functioning of the AVF. Careful analysis of the vascular network
      allows options for the development of new fistulas presentations. We present and
      discuss the case of a woman aged 69 years in HD in which a brachial-cephalic
      fistula with drainage to basilic vein was created, through rotation of the
      cephalic vein on the forearm level. This kind of access serves to prolong the
      time spent dialyzing through native fistulae, with their reduced complications
      and greater cost-effectiveness. 

PMID- 25950566
TI  - Amyloidogenic propensity of a natural variant of human apolipoprotein A-I:
      stability and interaction with ligands.
AB  - A number of naturally occurring mutations of human apolipoprotein A-I (apoA-I)
      have been associated with hereditary amyloidoses. The molecular mechanisms
      involved in amyloid-associated pathology remain largely unknown. Here we examined
      the effects of the Arg173Pro point mutation in apoA-I on the structure,
      stability, and aggregation propensity, as well as on the ability to bind to
      putative ligands. Our results indicate that the mutation induces a drastic loss
      of stability, and a lower efficiency to bind to phospholipid vesicles at
      physiological pH, which could determine the observed higher tendency to aggregate
      as pro-amyloidogenic complexes. Incubation under acidic conditions does not seem
      to induce significant desestabilization or aggregation tendency, neither does it
      contribute to the binding of the mutant to sodium dodecyl sulfate. While the
      binding to this detergent is higher for the mutant as compared to wt apoA-I, the
      interaction of the Arg173Pro variant with heparin depends on pH, being lower at
      pH 5.0 and higher than wt under physiological pH conditions. We suggest that
      binding to ligands as heparin or other glycosaminoglycans could be key events
      tuning the fine details of the interaction of apoA-I variants with the micro
      environment, and probably eliciting the toxicity of these variants in hereditary
      amyloidoses. 

PMID- 25950567
TI  - Use of culturally focused theoretical frameworks for adapting diabetes prevention
      programs: a qualitative review.
AB  - INTRODUCTION: Diabetes disproportionately affects underserved racial/ethnic
      groups in the United States. Diabetes prevention interventions positively
      influence health; however, further evaluation is necessary to determine what role
      culture plays in effective programming. We report on the status of research that
      examines cultural adaptations of diabetes prevention programs. METHODS: We
      conducted database searches in March and April 2014. We included studies that
      were conducted in the United States and that focused on diabetes prevention among
      African Americans, American Indians/Alaska Natives, Asian Americans/Pacific
      Islanders, and Latinos. RESULTS: A total of 58 studies were identified for
      review; 29 were excluded from evaluation. Few adaptations referenced or followed
      recommendations for cultural adaptation nor did they justify the content
      modifications by providing a rationale or evidence. Cultural elements unique to
      racial/ethnic populations were not assessed. CONCLUSION: Future cultural
      adaptations should use recommended processes to ensure that culture's role in
      diabetes prevention-related behavioral changes contributes to research.

PMID- 25950568
TI  - Evaluating diabetes mobile applications for health literate designs and
      functionality, 2014.
AB  - INTRODUCTION: The expansion of mobile health technologies, particularly for
      diabetes-related applications (apps), grew exponentially in the past decade. This
      study sought to examine the extent to which current mobile apps for diabetes have
      health literate features recommended by participants in an Institute of Medicine
      Roundtable and compare the health literate features by app cost (free or not).
      METHODS: We used diabetes-related keywords to identify diabetes-related apps for
      iOS devices. A random sample of 110 apps (24% of total number of apps identified)
      was selected for coding. The coding scheme was adapted from the discussion paper
      produced by participants in the Institute of Medicine Roundtable. RESULTS: Most
      diabetes apps in this sample addressed diabetes management and therapeutics, and
      paid apps were more likely than free apps to use plain language strategies, to
      label links clearly, and to have at least 1 feature (a "back" button) that helps
      with the organization. CONCLUSION: Paid apps were more likely than free apps to
      use strategies that should be more useful and engaging for people with low health
      literacy. Future work can investigate ways to make free diabetes mobile apps more
      user-friendly and accessible.

PMID- 25950569
TI  - Diabetes topics associated with engagement on Twitter.
AB  - INTRODUCTION: Social media are widely used by the general public and by public
      health and health care professionals. Emerging evidence suggests engagement with
      public health information on social media may influence health behavior. However,
      the volume of data accumulating daily on Twitter and other social media is a
      challenge for researchers with limited resources to further examine how social
      media influence health. To address this challenge, we used crowdsourcing to
      facilitate the examination of topics associated with engagement with diabetes
      information on Twitter. METHODS: We took a random sample of 100 tweets that
      included the hashtag "#diabetes" from each day during a constructed week in May
      and June 2014. Crowdsourcing through Amazon's Mechanical Turk platform was used
      to classify tweets into 9 topic categories and their senders into 3 Twitter user
      categories. Descriptive statistics and Tweedie regression were used to identify
      tweet and Twitter user characteristics associated with 2 measures of engagement,
      "favoriting" and "retweeting." RESULTS: Classification was reliable for tweet
      topics and Twitter user type. The most common tweet topics were medical and
      nonmedical resources for diabetes. Tweets that included information about
      diabetes-related health problems were positively and significantly associated
      with engagement. Tweets about diabetes prevalence, nonmedical resources for
      diabetes, and jokes or sarcasm about diabetes were significantly negatively
      associated with engagement. CONCLUSION: Crowdsourcing is a reliable, quick, and
      economical option for classifying tweets. Public health practitioners aiming to
      engage constituents around diabetes may want to focus on topics positively
      associated with engagement.

PMID- 25950570
TI  - Outside the exam room: policies for connecting clinic to community in diabetes
      prevention and treatment.
AB  - The public health burden and racial/ethnic, sex, and socioeconomic disparities in
      obesity and in diabetes require a population-level approach that goes beyond
      provision of high-quality clinical care. The Robert Wood Johnson Foundation's
      Commission to Build a Healthier America recommended 3 strategies for improving
      the nation's health: 1) invest in the foundations of lifelong physical and mental
      well-being in our youngest children; 2) create communities that foster health
      promoting behaviors; and 3) broaden health care to promote health outside the
      medical system. We present an overview of evidence supporting these approaches in
      the context of diabetes and suggest policies to increase investments in 1)
      adequate nutrition through breastfeeding and other supports in early childhood,
      2) community and economic development that includes health-promoting features of
      the physical, food, and social environments, and 3) evidence-based interventions
      that reach beyond the clinical setting to enlist community members in diabetes
      prevention and management. 

PMID- 25950571
TI  - Impact of the Affordable Care Act on access to care for US adults with diabetes,
      2011-2012.
AB  - INTRODUCTION: Lack of health insurance is a barrier to medical care, which may
      increase the risk of diabetes complications and costs. The objective of this
      study was to assess the potential of the Affordable Care Act (ACA) of 2010 to
      improve diabetes care through increased health care access by comparing health
      care and health outcomes of insured and uninsured people with diabetes. METHODS:
      We examined demographics, access to care, health care use, and health care
      expenditures of adults aged 19 to 64 years with diabetes by using the 2011 and
      2012 Medical Expenditure Panel Survey. Bivariate descriptive statistics comparing
      insured and uninsured persons were evaluated separately by income above and below
      138% of the federal poverty level (FPL), (a threshold for expanded Medicaid
      eligibility in select states under the ACA) using the t test and proportion and
      median tests. RESULTS: Uninsured adults reported poorer access to care than
      insured adults, such as having a usual source of health care (69.0% vs 89.5%
      [<=138% FPL], 77.1% vs 94.6% [>138% FPL], both P < .001) and having lower rates
      of 6 key diabetes preventive care services (P <= .05). Insured adults with
      diabetes had significantly higher health care expenditures than uninsured adults
      ($13,706 vs $4,367, $10,838 vs $4,419, respectively, both P < .001). CONCLUSION:
      Uninsured adults with diabetes had less access to health care and lower levels of
      preventive care, health care use, and expenditures than insured adults. To the
      extent that the ACA increases access and coverage, uninsured people with diabetes
      are likely to significantly increase their health care use, which may lead to
      reduced incidence of diabetes complications and improved health.

PMID- 25950572
TI  - Review of measures of worksite environmental and policy supports for physical
      activity and healthy eating.
AB  - INTRODUCTION: Obesity prevention strategies are needed that target multiple
      settings, including the worksite. The objective of this study was to assess the
      state of science concerning available measures of worksite environmental and
      policy supports for physical activity (PA) and healthy eating (HE). METHODS: We
      searched multiple databases for instruments used to assess worksite environments
      and policies. Two commonly cited instruments developed by state public health
      departments were also included. Studies that were published from 1991 through
      2013 in peer-reviewed publications and gray literature that discussed the
      development or use of these instruments were analyzed. Instrument administration
      mode and measurement properties were documented. Items were classified by general
      health topic, 5 domains of general worksite strategy, and 19 subdomains of
      worksite strategy specific to PA or HE. Characteristics of worksite measures were
      described including measurement properties, length, and administration mode, as
      well as frequencies of items by domain and subdomain. RESULTS: Seventeen
      instruments met inclusion criteria (9 employee surveys, 5 manager surveys, 1
      observational assessment, and 2 studies that used multiple administration modes).
      Fourteen instruments included reliability testing. More items were related to PA
      than HE. Most instruments (n = 10) lacked items in the internal social
      environment domain. The most common PA subdomains were exercise facilities and
      lockers/showers; the most common HE subdomain was healthy options/vending.
      CONCLUSION: This review highlights gaps in measurement of the worksite social
      environment. The findings provide a useful resource for researchers and
      practitioners and should inform future instrument development.

PMID- 25950573
TI  - Worksite influences on obesogenic behaviors in low-wage workers in St Louis,
      Missouri, 2013-2014.
AB  - INTRODUCTION: More than one-third of US adults are obese. Workplace programs to
      reduce obesity and improve overall health are not available or accessible to all
      workers, particularly low-wage workers among whom obesity is more prevalent. The
      goal of the study was to identify modifiable workplace factors and behaviors
      associated with diet and exercise to inform future workplace interventions to
      improve health. METHODS: We distributed paper and online surveys to 2 groups of
      low-wage workers, hospital workers and retail sales workers, at the worksites.
      The surveys assessed obesity, obesogenic behaviors, workplace factors, and worker
      participation in workplace health programs (WHPs). Descriptive and regression
      analyses were conducted to examine workplace factors associated with obesogenic
      behaviors. RESULTS: A total of 529 surveys were completed (219 hospital workers
      and 310 retail workers). More than 40% of workers were obese and 27% were
      overweight. In general, workers had poor diets (frequent consumption of sugary
      and high-fat foods) and engaged in little physical activity (only 30.9% met
      recommended physical activity guidelines). Access to and participation in
      workplace health programs varied greatly between hospital and retail sales
      workers. We identified several modifiable workplace factors, such as food source
      and work schedule, that were associated with diet, exercise, or participation in
      workplace health programs. CONCLUSION: This study illustrates the high prevalence
      of obesity and obesogenic behaviors workers in 2 low-wage groups. The differences
      between work groups indicated that each group had unique facilitators and
      barriers to healthy eating and exercise. An understanding of how socioeconomic,
      demographic, and work-related factors influence health will help to identify high
      risk populations for intervention and to design interventions tailored and
      relevant to the target audiences.

PMID- 25950574
TI  - Enhancing workplace wellness efforts to reduce obesity: a qualitative study of
      low-wage workers in St Louis, Missouri, 2013-2014.
AB  - INTRODUCTION: The objective of this study was to examine workplace determinants
      of obesity and participation in employer-sponsored wellness programs among low
      wage workers. METHODS: We conducted key informant interviews and focus groups
      with 2 partner organizations: a health care employer and a union representing
      retail workers. Interviews and focus groups discussed worksite factors that
      support or constrain healthy eating and physical activity and barriers that
      reduce participation in workplace wellness programs. Focus group discussions were
      transcribed and coded to identify main themes related to healthy eating, physical
      activity, and workplace factors that affect health. RESULTS: Although the union
      informants recognized the need for workplace wellness programs, very few programs
      were offered because informants did not know how to reach their widespread and
      diverse membership. Informants from the health care organization described
      various programs available to employees but noted several barriers to effective
      implementation. Workers discussed how their job characteristics contributed to
      their weight; irregular schedules, shift work, short breaks, physical job
      demands, and food options at work were among the most commonly discussed
      contributors to poor eating and exercise behaviors. Workers also described
      several general factors such as motivation, time, money, and conflicting
      responsibilities. CONCLUSION: The workplace offers unique opportunities for
      obesity interventions that go beyond traditional approaches. Our results suggest
      that modifying the physical and social work environment by using participatory or
      integrated health and safety approaches may improve eating and physical activity
      behaviors. However, more research is needed about the methods best suited to the
      needs of low-wage workers.

PMID- 25950575
TI  - Influence of home and school environments on specific dietary behaviors among
      postpartum, high-risk teens, 27 States, 2007-2009.
AB  - INTRODUCTION: The objective of this study was to determine whether perceptions of
      the home and school food environments are related to food and beverage intakes of
      postpartum teens. METHODS: Our study was a baseline, cross-sectional analysis of
      853 postpartum teens enrolled in a weight-loss intervention study across 27
      states from 2007 through 2009. Eight-item scales assessed perceived accessibility
      and availability of foods and beverages in school and home environments.
      Associations between environments and intakes were assessed by using chi(2) and
      using logistic regression with generalized estimating equations (GEE),
      respectively. RESULTS: Overall, 52% of teens perceived their school food
      environment as positive, and 68% of teens perceived their home food environment
      as positive. A positive school environment was independently associated with
      fruit consumption and 100% fruit juice consumption. A positive home environment
      was independently associated with fruit, vegetable, and water consumption and
      infrequent consumption of soda and chips (chi(2) P < .05). Having only a positive
      school environment was associated with fruit consumption (GEE odds ratio [OR],
      3.1; 95% confidence interval [CI], 1.5-6.5), and having only a positive home
      environment was associated with fruit (GEE OR, 2.9; 95% CI, 1.6-5.6), vegetable
      (GEE OR, 3.1; 95% CI, 1.5-6.2), and water (GEE OR, 2.6; 95% CI, 1.7-4.0)
      consumption and infrequent consumption of soda (GEE OR, 0.5; 95% CI, 0.3-0.7).
      Results for positive home and school environments were similar to those for
      positive home only. CONCLUSION: Home and school environments are related to
      dietary behaviors among postpartum teens, with a positive home environment more
      strongly associated with healthful behaviors.

PMID- 25950576
TI  - A longitudinal study of structural risk factors for obesity and diabetes among
      American Indian young adults, 1994-2008.
AB  - INTRODUCTION: American Indian young adults have higher rates of obesity and type
      2 diabetes than the general US population. They are also more likely than the
      general population to have higher rates of structural risk factors for obesity
      and diabetes, such as poverty, frequent changes of residence, and stress. The
      objective of this study was to investigate possible links between these 2 sets of
      problems. METHODS: Data from the American Indian subsample of the National
      Longitudinal Study of Adolescent to Adult Health (Add Health) were used to
      examine potential links between obesity and type 2 diabetes and structural risk
      factors such as neighborhood poverty, housing mobility, and stress. We used
      logistic regression to explore explanatory factors. RESULTS: American Indians in
      the subsample had higher rates of poor health, such as elevated hemoglobin A1c
      levels, self-reported high blood glucose, self-reported diabetes, and overweight
      or obesity. They also had higher rates of structural risk factors than non
      Hispanic whites, such as residing in poorer and more transient neighborhoods and
      having greater levels of stress. Self-reported stress partially mediated the
      increased likelihood of high blood glucose or diabetes among American Indians,
      whereas neighborhood poverty partially mediated their increased likelihood of
      obesity. CONCLUSION: Neighborhood poverty and stress may partially explain the
      higher rates of overweight, obesity, and type 2 diabetes among American Indian
      young adults than among non-Hispanic white young adults. Future research should
      explore additional neighborhood factors such as access to grocery stores selling
      healthy foods, proximity and safety of playgrounds or other recreational space,
      and adequate housing.

PMID- 25950577
TI  - Relationship between abuse and neglect in childhood and diabetes in adulthood:
      differential effects by sex, national longitudinal study of adolescent health.
AB  - INTRODUCTION: Few studies have investigated links between child abuse and neglect
      and diabetes mellitus in nationally representative samples, and none have
      explored the role of obesity in the relationship. We sought to determine whether
      child abuse and neglect were associated with diabetes and if so, whether obesity
      mediated this relationship in a population-representative sample of young adults.
      METHODS: We used data from 14,493 participants aged 24 to 34 years from Wave IV
      of the National Longitudinal Study of Adolescent Health to study associations
      between self-reported child abuse (sexual, physical, or emotional abuse) and
      neglect as children and diabetes or prediabetes in young adulthood. We conducted
      sex-stratified logistic regression analyses to evaluate associations in models
      before and after the addition of body mass index (BMI) as a covariate. RESULTS:
      Although the prevalence of diabetes was similar for men and women (7.0% vs 6.7%),
      men were more likely than women to have prediabetes (36.3% vs 24.6%; omnibus P <
      .001). Among men, recurrent sexual abuse (>=3 lifetime incidents) was
      significantly associated with diabetes (OR, 3.66; 95% CI, 1.31-10.24), but not
      with prediabetes. There was no evidence of mediation by BMI. No forms of child
      abuse or neglect were associated with diabetes or prediabetes among women.
      CONCLUSIONS: Recurrent sexual abuse is robustly associated with diabetes in young
      adult men, independently of other forms of child abuse or neglect and BMI. Future
      research should explore other potential mechanisms for this association to
      identify avenues for prevention of diabetes among men who have experienced sexual
      abuse.

PMID- 25950578
TI  - Next steps: eliminating disparities in diabetes and obesity.

PMID- 25950579
TI  - Is female gender as harmful as bacteria? analysis of hospital admissions for
      urinary tract infections in elderly patients.
AB  - BACKGROUND: Urinary tract infections (UTIs) are common bacterial diseases. We
      related diagnosis of UTIs based on International Classification of Diseases, 9th
      Revision, Clinical Modification (ICD-9-CM) and in-hospital mortality (IHM) in a
      cohort of hospitalized elderly subjects. METHODS: All patients admitted between
      2000 and 2013 to the general hospital of Ferrara, in northeast Italy, with ICD-9
      CM code of UTIs were included. IHM was the main outcome, and age, sex, type of
      microorganism, sepsis, and Charlson comorbidity index (CCI) based on ICD-9-CM,
      were also analyzed. RESULTS: The total sample included 2,266 patients (1,670
      women, 73.7%) with UTIs and identification of a cultural organism. Mean age was
      81.7+/-7.5 years (range, 65-103). One hundred and sixteen (5.1%, of whom 34.5%
      were male and 65.5% were female) cases developed sepsis, and 84 (3.7%, of whom
      45.2% were male, 54.8% were female) had a fatal outcome. Nonsurvivors had lower
      prevalence of IVUs due to Escherichia coli (53.6 vs. 71.7%, p<0.001) and higher
      prevalence of UTIs due to Pseudomonas aeruginosa (19 vs 7.1%, p<0.001). Moreover,
      non-survivors developed more frequently sepsis (31% vs. 4.1%, p<0.001), and had
      higher CCI (2.81+/-2.43 vs. 2.21+/-2.04, p=0.011). IHM was independently
      associated, in decreasing order of odds ratios (ORs), with sepsis (OR 10.3; 95%
      confidence interval [95% CI] 6.113-17.460, p<0.001), P. aeruginosa infection (OR
      2.541; 95% CI 1.422-4.543, p=0.002), female gender (OR 2.324; 95% CI 1.480-3.650,
      p<0.001), CCI (OR 1.103; 95% CI 1.005-1.210, p=0.038), age (OR 1.034; 95% CI
      1.002-1.066, p=0.036), and E. coli infection (OR 0.5; 95% CI 0.320-0.780,
      p=0.002). CONCLUSIONS: In a large sample of elderly patients hospitalized for
      UTIs in a single center in northeastern Italy, apart the development of sepsis,
      IHM was much more dependent on pathogen and female gender than comorbidity index
      and age.

PMID- 25950580
TI  - Nurses do not have proprietary rights on caring: but we do on clinical practice
      models.

PMID- 25950581
TI  - MtDNA Haplogroup A10 Lineages in Bronze Age Samples Suggest That Ancient
      Autochthonous Human Groups Contributed to the Specificity of the Indigenous West
      Siberian Population.
AB  - BACKGROUND: The craniometric specificity of the indigenous West Siberian human
      populations cannot be completely explained by the genetic interactions of the
      western and eastern Eurasian groups recorded in the archaeology of the area from
      the beginning of the 2nd millennium BC. Anthropologists have proposed another
      probable explanation: contribution to the genetic structure of West Siberian
      indigenous populations by ancient human groups, which separated from western and
      eastern Eurasian populations before the final formation of their phenotypic and
      genetic features and evolved independently in the region over a long period of
      time. This hypothesis remains untested. From the genetic point of view, it could
      be confirmed by the presence in the gene pool of indigenous populations of
      autochthonous components that evolved in the region over long time periods. The
      detection of such components, particularly in the mtDNA gene pool, is crucial for
      further clarification of early regional genetic history. RESULTS AND CONCLUSION:
      We present the results of analysis of mtDNA samples (n = 10) belonging to the A10
      haplogroup, from Bronze Age populations of West Siberian forest-steppe (V-I
      millennium BC), that were identified in a screening study of a large diachronic
      sample (n = 96). A10 lineages, which are very rare in modern Eurasian
      populations, were found in all the Bronze Age groups under study. Data on the A10
      lineages' phylogeny and phylogeography in ancient West Siberian and modern
      Eurasian populations suggest that A10 haplogroup underwent a long-term evolution
      in West Siberia or arose there autochthonously; thus, the presence of A10
      lineages indicates the possible contribution of early autochthonous human groups
      to the genetic specificity of modern populations, in addition to contributions of
      later interactions of western and eastern Eurasian populations.

PMID- 25950582
TI  - PARP2 Is the Predominant Poly(ADP-Ribose) Polymerase in Arabidopsis DNA Damage
      and Immune Responses.
AB  - Poly (ADP-ribose) polymerases (PARPs) catalyze the transfer of multiple poly(ADP
      ribose) units onto target proteins. Poly(ADP-ribosyl)ation plays a crucial role
      in a variety of cellular processes including, most prominently, auto-activation
      of PARP at sites of DNA breaks to activate DNA repair processes. In humans, PARP1
      (the founding and most characterized member of the PARP family) accounts for more
      than 90% of overall cellular PARP activity in response to DNA damage. We have
      found that, in contrast with animals, in Arabidopsis thaliana PARP2 (At4g02390),
      rather than PARP1 (At2g31320), makes the greatest contribution to PARP activity
      and organismal viability in response to genotoxic stresses caused by bleomycin,
      mitomycin C or gamma-radiation. Plant PARP2 proteins carry SAP DNA binding motifs
      rather than the zinc finger domains common in plant and animal PARP1 proteins.
      PARP2 also makes stronger contributions than PARP1 to plant immune responses
      including restriction of pathogenic Pseudomonas syringae pv. tomato growth and
      reduction of infection-associated DNA double-strand break abundance. For poly(ADP
      ribose) glycohydrolase (PARG) enzymes, we find that Arabidopsis PARG1 and not
      PARG2 is the major contributor to poly(ADP-ribose) removal from acceptor
      proteins. The activity or abundance of PARP2 is influenced by PARP1 and PARG1.
      PARP2 and PARP1 physically interact with each other, and with PARG1 and PARG2,
      suggesting relatively direct regulatory interactions among these mediators of the
      balance of poly(ADP-ribosyl)ation. As with plant PARP2, plant PARG proteins are
      also structurally distinct from their animal counterparts. Hence core aspects of
      plant poly(ADP-ribosyl)ation are mediated by substantially different enzymes than
      in animals, suggesting the likelihood of substantial differences in regulation. 

PMID- 25950584
TI  - Intimate Partner Violence Among Women Diagnosed With Cancer.
AB  - BACKGROUND: There is growing evidence that women diagnosed with cancer can
      experience intimate partner violence (IPV). This combined experience of cancer
      and abuse can have a profound effect on health and treatment outcomes for these
      cancer survivors. OBJECTIVE: The purpose of this literature review was to assess
      the presence of IPV among female cancer survivors and to provide oncology nurses
      with clinical guidelines about IPV. METHODS: A systematic strategy was used to
      locate original research from 4 databases: CINAHL, PubMed, PsycINFO, and Web of
      Science. Key words were used to help identify articles that focused on cancer,
      abuse, treatment decision making, and clinical guidelines. RESULTS: The 10
      selected articles that met the inclusion criteria were published between 2005 and
      2014. The reviewed studies provided accounts of abusive partner behaviors toward
      women throughout their cancer trajectory. Global organizations provided the
      framework for clinical guidelines. CONCLUSIONS: Challenges faced by women who are
      concurrently living with IPV and cancer survivorship can impact treatment
      decision making and health outcomes. The assessment and recognition of IPV by
      oncology nurses are essential to help create a clinical environment in which
      patients feel safe and supported. IMPLICATIONS FOR PRACTICE: This review includes
      clinical guidelines and describes legal considerations for oncology nurses to
      consider when they address and respond to IPV in their practice. The use of
      clinical guidelines that focus on IPV can provide standardized care in the
      oncology setting that can further help to meet the needs of these women.

PMID- 25950583
TI  - Adolescent and Young Adult Survivors of Childhood Brain Tumors: Life After
      Treatment in Their Own Words.
AB  - BACKGROUND: To date, there are few studies that examine the perspectives of older
      survivors of childhood brain tumors who are living with their families in terms
      of their sense of self and their role in their families. OBJECTIVE: The aim of
      this study was to describe how adolescent and young adult survivors of childhood
      brain tumors describe their health-related quality of life, that is, their
      physical, emotional, and social functioning. METHODS: This qualitative
      descriptive study included a purposive sample of 41 adolescent and young adult
      survivors of a childhood brain tumor who live with their families. Home
      interviews were conducted using a semistructured interview guide. Directed
      content analytic techniques were used to analyze data using health-related
      quality of life as a framework. RESULTS: This group of brain tumor survivors
      described their everyday lives in terms of their physical health, neurocognitive
      functioning, emotional health, social functioning, and self-care abilities.
      Overall, survivors struggle for normalcy in the face of changed functioning due
      to their cancer and the (late) effects of their treatment. CONCLUSIONS:
      Neurocognitive issues seemed most compelling in the narratives. The importance of
      families went beyond the resources, structure, and support for functioning. Their
      families provided the recognition that they were important beings and their
      existence mattered to someone. IMPLICATIONS FOR PRACTICE: The value and
      complexity of care coordination were highlighted by the multifaceted needs of the
      survivors. Advocacy for appropriate and timely educational, vocational, and
      social support is critical as part of comprehensive cancer survivorship care.

PMID- 25950585
TI  - The role of nurses/social workers in using a multidimensional guideline for
      diagnosis of anxiety and challenging behaviour in people with intellectual
      disabilities.
AB  - AIMS AND OBJECTIVES: This study seeks (1) to investigate the impact of the
      implementation of the 'Diagnostic Guideline for Anxiety and challenging
      behaviours in clients with intellectual disability' on nurses/social workers'
      knowledge and self-efficacy; and (2) to evaluate the role of nurses/social
      workers in the diagnostic process when applying the guideline. BACKGROUND:
      Nurses/social workers have extensive contact with clients with intellectual
      disabilities. Despite this key position, the contribution of nurses/social
      workers to the diagnosis of mental health problems and challenging behaviours is
      rather limited. The authors developed the multidimensional 'Diagnostic Guideline
      for Anxiety and challenging behaviours'. In this article, the implementation of
      this guideline is evaluated concerning knowledge and self-efficacy of
      nurses/social workers, as well the role of nurses/social workers in the
      diagnostic process. DESIGN: This study employed a comparative multiple case study
      design. METHODS: Qualitative and quantitative research methods. RESULTS: Working
      with the 'Diagnostic Guideline for Anxiety and challenging behaviours' led to a
      statistically significant increase in knowledge and self-efficacy among the
      nurses/social workers in the experimental condition, compared with nurses/social
      workers in the control condition. Nurses/social workers and psychologists
      appreciated the more active contribution of the nurses/social workers in the
      diagnostic process. CONCLUSIONS: Working with the guideline increased the
      knowledge and self-efficacy of nurses/social workers, and led to more active
      participation of nurses/social workers in the diagnostic process. RELEVANCE TO
      CLINICAL PRACTICE: After following a training programme, nurses/social workers
      can effectively contribute to the diagnostic process in clients with anxiety and
      related challenging behaviours.

PMID- 25950586
TI  - Ossifying fibromyxoid tumor: a clinicopathologic analysis of 26 subcutaneous
      tumors with emphasis on differential diagnosis and prognostic factors.
AB  - INTRODUCTION: Ossifying fibromyxoid tumor (OFMT) is rare and may present
      diagnostic difficulty. We describe 26 subcutaneous examples of OFMT emphasizing
      differential diagnosis and prognostic features. METHODS: Histopathology and
      follow-up data from archival/consultation cases were reviewed. Prognostic
      features were assessed according to proposed criteria. RESULTS: Patients (16
      female, 10 male) ranged from 26 to 88 years (median 54). The tumors (median 2.3
      cm, range 0.8-8.5) involved lower limb (11), trunk (7), head/neck (4), or arm
      (4). All showed combinations of corded, nested and trabecular patterns in a
      fibromyxoid stroma. Out of 26 cases 13 had peripheral ossification. Sixteen of 22
      cases showed S100 protein expression. Nuclear grade was low (14); intermediate
      (8) and high (4) while cellularity was low (14); moderate (7) and high (5), with
      overall good interobserver agreement. Median mitotic rate was 3/50HPF (0-61).
      Five met criteria for malignant OFMT showing high nuclear grade or high
      cellularity and mitotic rate >2/50HPF or both. Thirteen OFMTs were atypical.
      Follow-up (16/26, median 45.5 months, range 8-108) showed that patients with
      typical OFMT (3) and atypical OFMT (9) remained disease-free. Three malignant
      examples of OFMT recurred and one metastasized to the lung. No deaths were
      recorded. CONCLUSIONS: Our results validate proposed prognostic classification of
      OFMT. Dermatopathologists should be aware of this unusual superficial tumor given
      its potentially aggressive behavior.

PMID- 25950588
TI  - Smoke your troubles away: exploring the effects of death cognitions on cannabis
      craving and consumption.
AB  - Two studies informed by the terror management health model were conducted to
      examine the question of how death cognition affects cannabis craving and whether
      actual cannabis smoking alleviates death cognitions. The first study examined
      whether priming thoughts of death are associated with subjective cannabis craving
      among 42 frequent cannabis users randomly assigned to either a mortality salience
      or control task. When reminded of their death, participants craved cannabis, even
      though there was no change in their conscious negative mood. The second study
      examined the effect of cannabis smoking on death cognitions in an exploratory
      field setting. Fifty frequent cannabis users were randomly assigned to either
      mortality reminders or control task and completed death-related words
      accessibility measures before and after smoking cannabis. Results indicate that
      cannabis served as a buffer and prevented death-related thoughts from entering
      consciousness, thus acting as a defense mechanism against death anxiety. These
      findings indicate that death-related concerns may play a hitherto unsuspected
      role in cannabis craving and consumption. Also discussed are the implications of
      a terror management perspective in communication of negative health consequences
      of recreational cannabis smoking and in the use of cannabis for medical purposes
      among people with terminal illness. 

PMID- 25950589
TI  - Marijuana use, motives, and change intentions in adolescents.
AB  - Research typically focuses on motives to use or abstain from marijuana (MJ) in
      isolation; few studies have integrated both constructs in models of MJ use
      decision making. We expand the existing literature by integrating these motives
      in cognitive models of use and cessation in adolescents. We expected use motives
      to account for past use and intentions for future use, and for motives to abstain
      to dominate models explaining intention, desire, and self-efficacy for quitting.
      Adolescent MJ users (N = 162) reported their use and abstinence motives as well
      as their use and cessation behavior via online survey conducted in high schools.
      Past use was related to high conformity and low coping, while past cessation
      attempts were related to high enhancement motives. Intentions to use were related
      to low negative consequences and conformity, and high enhancement and expansion
      motives to use. Quitting intention was related to social motives to use, as was
      quitting self-efficacy. Self-efficacy was also related to high personal/peer
      beliefs motives to abstain. While past MJ use and intended future use were almost
      exclusively accounted for by use motives, both motives to use and abstain
      impacted self-reported cognitions associated with cessation in this sample of
      adolescent MJ users. 

PMID- 25950587
TI  - MicroRNA-21 Regulates PI3K/Akt/mTOR Signaling by Targeting TGFbetaI during
      Skeletal Muscle Development in Pigs.
AB  - MicroRNAs (miRNAs), which are short (22-24 base pairs), non-coding RNAs, play
      critical roles in myogenesis. Using Solexa deep sequencing, we detected the
      expression levels of 229 and 209 miRNAs in swine skeletal muscle at 90 days post
      coitus (E90) and 100 days postnatal (D100), respectively. A total of 138 miRNAs
      were up-regulated on E90, and 31 were up-regulated on D100. Of these, 9 miRNAs
      were selected for the validation of the small RNA libraries by quantitative RT
      PCR (RT-qPCR). We found that miRNA-21 was down-regulated by 17-fold on D100
      (P<0.001). Bioinformatics analysis suggested that the transforming growth factor
      beta-induced (TGFbetaI) gene was a potential target of miRNA-21. Both dual
      luciferase reporter assays and western blotting demonstrated that the TGFbetaI
      gene was regulated by miRNA-21. Co-expression analysis revealed that the mRNA
      expression levels of miRNA-21 and TGFbetaI were negatively correlated (r = 
      0.421, P = 0.026) in skeletal muscle during the 28 developmental stages. Our
      results revealed that more miRNAs are expressed in prenatal than in postnatal
      skeletal muscle. The miRNA-21 is a novel myogenic miRNA that is involved in
      skeletal muscle development and regulates PI3K/Akt/mTOR signaling by targeting
      the TGFbetaI gene. 

PMID- 25950590
TI  - Cannabis use and quality of life of adolescents and young adults: findings from
      an Australian birth cohort.
AB  - Cannabis is generally used to enhance mood (quality of life), but it is not known
      whether it has this effect in the medium to longer term. Little is currently
      known about the temporal sequence between cannabis use and the quality of life
      (QOL). Data are taken from a prospective longitudinal study of pregnant women
      recruited at their first antenatal visit in Brisbane, Australia. Offspring data
      from the follow-ups with 14-year-olds and 21-year-olds are used here. Indicators
      of QOL, happiness, and satisfaction at 14 years are considered as predictors of
      subsequent cannabis use. The association between cannabis use and QOL at 21
      years, adjusting for prior QOL (14 years), is also examined. Socio-demographic
      characteristics were included as potential confounders relevant to QOL
      assessments. In this cohort, lower QOL in the early teenage years predicted
      subsequent onset of cannabis use in young adulthood. After adjustment for socio
      demographic characteristics and for QOL pre-cannabis use, participants who used
      cannabis more frequently had a lower QOL at the 21-years follow-up. Frequent use
      of cannabis does not appear to enhance the user's QOL and appears to be
      associated with a reduced QOL into young adulthood. 

PMID- 25950591
TI  - Lifetime influences for cannabis cessation in male incarcerated indigenous
      australians.
AB  - INTRODUCTION: Urban non-indigenous populations report life events (marriages,
      employment) as influences for self-initiated cannabis cessation. However, this
      hasn't been investigated in remote indigenous populations with different social
      paradigms. METHODS: We investigate cannabis use, harms, and poly-substance misuse
      in 101 consenting male incarcerated indigenous Australians. Interviews applied
      quantitative and qualitative questions assessing demographic characteristics,
      criminal history, drug use, the Marijuana Problems Inventory (MPI), and cannabis
      cessation influences. Comparisons used Chi Square, Analysis of Variance, and
      Nvivo software. RESULTS: Cannabis use groups (current users, ex-users, and never
      users) were demographically similar except that current users reported more
      juvenile legal problems, younger school departure, and lower school achievement
      (p < 0.05). Mean cannabis consumption was 12.3 cones/day. Incarceration and
      family responsibilities were the strongest cessation influences. Employment
      responsibilities and negative self-image were rarely cited as influences.
      DISCUSSION: High cannabis use, with its associated problems, is concerning. These
      identified influences indicate incarceration should be used for substance
      reduction programs, plus post-release follow-up. Community-based programs
      focusing on positive influences, such as family responsibilities and social
      cohesion, may be successful within indigenous populations with strong kinship
      responsibilities, rather than programs that focus solely on substance harms.

PMID- 25950592
TI  - Social Functioning of Kratom (Mitragyna speciosa) Users in Malaysia.
AB  - Kratom (Mitragyna speciosa) is an indigenous plant known for its traditional
      medicinal use, and for its addiction potential, in Southeast Asia. In recent
      years, kratom and its major alkaloid, mitragynine, spread worldwide with largely
      unknown effects on behavior and mental health. Recent studies show that kratom
      use can lead to dependence and that mitragynine works as an addictive drug in
      animal studies. Nevertheless, kratom preparations were also suggested as a less
      harmful substitute in opiate withdrawal. Potential side-effects of prolonged
      kratom use, however, are currently unclear. The aim of this study was to
      investigate the social functioning of regular kratom users in Malaysia. A cross
      sectional survey was carried out in three northern states of Peninsular Malaysia
      investigating 293 regular kratom consumers using the Addiction Severity Index in
      a snowball sampling technique. Findings showed that regular kratom users do not
      experience major impairments in their social functioning, despite being dependent
      on kratom for prolonged periods. Our findings suggest that chronic kratom
      administration does not significantly impair social functioning of users in a
      natural context in Malaysia. 

PMID- 25950593
TI  - Ritualistic Use of Ayahuasca versus Street Use of Similar Substances Seized by
      the Police: A Key Factor Involved in the Potential for Intoxications and
      Overdose?
AB  - The ritualistic use of ayahuasca is becoming a global phenomenon. This beverage
      contains a combination of monoamine oxidase inhibitors (harmine, harmaline, and
      tetrahydroharmine) and N,N-dimethyltryptamine, the main substance responsible for
      its visionary effect. The recreational use of similar alkaloids and N,N
      dimethyltryptamine has increased in recent years, mainly because of their
      hallucinogenic effects. In the present study, the concentrations of psychoactive
      alkaloids in three powder samples seized by the Sao Paulo State Police and nine
      ayahuasca aqueous extracts were analyzed by HPLC-DAD in an attempt to distinguish
      between illicit drugs and the religious beverage. The alkaloids detected (MUg/mL)
      in the ayahuasca aqueous extracts were N,N-dimethyltryptamine (402-2070.3),
      harmaline (27.5-181.3), harmine (294.5-2893.8), and tetrahydroharmine (849.5
      2052.5), whereas, of the three powder samples, one contained only N,N
      dimethyltryptamine (82% and 2% w/w, respectively) while the other contained only
      harmaline (16%, w/w) and harmine (12%, w/w). The ritualistic use of ayahuasca
      involves oral intake and the probability of overdose is minimized by serotonergic
      stimulation of vagal pathways, leading to vomiting and diarrhea. In contrast, the
      recreational use of N,N-dimethyltryptamine involves consumption mainly by smoking
      or inhalation, both of which markedly increase its bioavailability and the
      potential for intoxications. 

PMID- 25950594
TI  - Novel psychoactive substance and other drug use by young adults in Western
      australia.
AB  - There is a lack of information regarding the use of novel psychoactive substances
      (NPS) in Western Australia. The aim of this study was to pilot-test an online
      survey to obtain data on the prevalence of NPS and other drug use by young
      Western Australians aged between 18 and 35 years. The Young Adult Drug and
      Alcohol Survey (YADAS) was a questionnaire deployed online for a period of six
      months. Participants were recruited via a combined targeted sampling and snowball
      methodology. There were 472 valid responses. Overall lifetime use of NPS was
      relatively high (17.6%), while use in the last year was lower (6.6%). These
      proportions were comparable to that of cocaine use. The most popular NPS were the
      synthetic cannabinoids. The proportions of respondents drinking alcohol at risky
      levels, mixing alcohol with energy drinks, and using pharmaceuticals such as ADHD
      medications for non-medical reasons were high. The YADAS is the first survey to
      ascertain the prevalence of use of numerous types of NPS in a large sample of
      young Western Australian adults. The utilization of an online survey methodology
      yielded valid results as compared to more intensive surveys, and enables
      researchers greater flexibility in being able to capture current trends. 

PMID- 25950595
TI  - Changes in Quality of Life following Buprenorphine Treatment: Relationship with
      Treatment Retention and Illicit Opioid Use.
AB  - Studies of substance abuse treatment outcomes that give priority to cessation of
      all drug use may obscure other tangible benefits of treatment that are important
      to patients. The aim of this study was to examine the association between changes
      in quality of life (QoL) and: (1) retention in treatment; and (2) opioid use as
      measured by self-report and urine testing. Participants were 300 African American
      men and women starting outpatient buprenorphine treatment. Participants completed
      assessments at baseline, three and six months consisting of the World Health
      Organization's Quality of Life brief scale, Addiction Severity Index, and urine
      testing for opioids. There were statistically significant increases over time
      across all four QoL domains: physical, psychological, environmental, and social.
      Self-reported frequency of opioid use was negatively associated with
      psychological QoL, but opioid urine test results were not significantly
      associated with any QoL domains. Continued treatment enrollment was significantly
      associated with higher psychological QoL and environmental QoL. Patients entering
      buprenorphine treatment experience improvements in QoL, which are amplified for
      patients who remain in treatment. Point-prevalence opiate urine test results
      obtained at each assessment were not associated with any of the QoL domains and
      may not accurately reflect improvements perceived by patients receiving
      buprenorphine treatment. 

PMID- 25950597
TI  - Basal level of autophagy is increased in aging human skin fibroblasts in vitro,
      but not in old skin.
AB  - Intracellular autophagy (AP) is a stress response that is enhanced under
      conditions of limitation of amino acids, growth factors and other nutrients, and
      also when macromolecules become damaged, aggregated and fibrillated. Aging is
      generally accompanied by an increase in intracellular stress due to all the above
      factors. Therefore, we have compared the basal levels of AP in serially passaged
      human facial skin fibroblasts undergoing aging and replicative senescence in
      vitro, and ex vivo in the skin biopsies from the photo-protected and photo
      exposed area of the arms of 20 healthy persons of young and old ages.
      Immunofluorescence microscopy, employing antibodies against a specific
      intracellular microtubule-associated protein-1 light chain-3 (LC3) as a well
      established marker of AP, showed a 5-fold increase in the basal level of LC3 in
      near senescent human skin fibroblasts. However, no such age-related increase in
      LC3 fluorescence and AP could be detected in full thickness skin sections from
      the biopsies obtained from 10 healthy young (age 25 to 30 yr) and 10 old (age 60
      to 65 yr) donors. Furthermore, there was no difference in the basal level of LC3
      in the skin sections from photo-protected and photo-exposed areas of the arm.
      Thus, in normal conditions, the aging phenotype of the skin cells in culture and
      in the body appears to be different in the case of AP. 

PMID- 25950596
TI  - Text messaging for addiction: a review.
AB  - Individuals seeking treatment for addiction often experience barriers due to
      cost, lack of local treatment resources, or either school or work schedule
      conflicts. Text-messaging-based addiction treatment is inexpensive and has the
      potential to be widely accessible in real time. We conducted a comprehensive
      literature review identifying 11 published, randomized controlled trials (RCTs)
      evaluating text-messaging-based interventions for tobacco smoking, four studies
      for reducing alcohol consumption, one pilot study in former methamphetamine (MA)
      users, and one study based on qualitative interviews with cannabis users.
      Abstinence outcome results in RCTs of smokers willing to make a quit attempt have
      been positive overall in the short term and as far out as at six and 12 months.
      Studies aimed at reducing alcohol consumption have been promising. More data are
      needed to evaluate the feasibility, acceptability, and efficacy of this approach
      for other substance use problems. 

PMID- 25950598
TI  - The development and application of a multiplex short tandem repeat (STR) system
      for identifying subspecies, individuals and sex in tigers.
AB  - Poaching and trans-boundary trafficking of tigers and body parts are threatening
      the world's last remaining wild tigers. Development of an efficient molecular
      genetic assay for tracing the origins of confiscated specimens will assist in law
      enforcement and wildlife forensics for this iconic flagship species. We developed
      a multiplex genotyping system "tigrisPlex" to simultaneously assess 22 short
      tandem repeat (STR, or microsatellite) loci and a gender-identifying SRY gene,
      all amplified in 4 reactions using as little as 1 ng of template DNA. With DNA
      samples used for between-run calibration, the system generates STR genotypes that
      are directly compatible with voucher tiger subspecies genetic profiles, hence
      making it possible to identify subspecies via bi-parentally inherited markers. We
      applied "tigrisPlex" to 12 confiscated specimens from Russia and identified 6
      individuals (3 females and 3 males), each represented by duplicated samples and
      all designated as Amur tigers (Panthera tigris altaica) with high confidence.
      This STR multiplex system can serve as an effective and versatile approach for
      genetic profiling of both wild and captive tigers as well as confiscated tiger
      products, fulfilling various conservation needs for identifying the origins of
      tiger samples. 

PMID- 25950599
TI  - Multivalent targeting of AT1 receptors with angiotensin II-functionalized
      nanoparticles.
AB  - The angiotensin II receptor type 1 (AT1R) is a G protein-coupled receptor of
      paramount significance since it is overexpressed in a number of diseased tissues
      that are highly attractive for nanoparticle targeting. However, it is also
      expressed at physiological levels in healthy tissue. Multivalent interactions
      mediated by multiple AT1R-binding moieties per nanoparticle could promote a high
      binding avidity to AT1R overexpressing cells and concomitantly spare off-target
      tissue. To investigate the feasibility of this approach, angiotensin II was
      thiolated and conjugated to PEGylated quantum dots. Nanoparticle binding, uptake
      and affinity to several cell lines was investigated in detail. The colloids were
      rapidly taken up by clathrin-mediated endocytosis into AT1R-expressing cells and
      showed no interaction with receptor negative cells. The EC50 of the thiolated
      angiotensin II was determined to be 261 nM, whereas the ligand-conjugated Qdots
      activated the receptor with an EC50 of 8.9 nM. This 30-fold higher affinity of
      the nanoparticles compared to the unconjugated peptide clearly demonstrated the
      presence of multivalent effects when using agonist-targeted nanoparticles. Our
      study provides compelling evidence that, despite being immediately endocytosed,
      Ang II-coupled nanoparticles exert potent multivalent ligand-receptor
      interactions that can be used to establish high affinities to an AT1R
      overexpressing cell and tissue. 

PMID- 25950600
TI  - The human Nox4: gene, structure, physiological function and pathological
      significance.
AB  - Increased generation of reactive oxygen species (ROS) has been implicated in the
      pathogenesis of a variety of diseases such as cardiovascular diseases and cancer.
      NADPH oxidase (Nox), a multicomponent enzyme, has been identified as one of the
      key sources of ROS. Nox4, one of the seven members of Nox family (Nox1, Nox2,
      Nox3, Nox4, Nox5, Duox1 and Duox2), has been extensively investigated in recent
      years. Its unique structures result in the constitutive generation of hydrogen
      peroxide (H2O2) as the main product. As a key oxygen sensor, Nox4-derived H2O2
      plays diverse roles in cell proliferation, migration and death. Increased
      expression of Nox4 in cancer has been observed, which participates in metastasis,
      angiogenesis and apoptosis. Expression of Nox4 in endothelial cells actively
      mediated endothelial activation, dysfunction and injury, which contributes to the
      development of atherosclerosis, hypertension, cardiac hypertrophy and among
      others. This article explores the experimental studies related to the gene,
      structure, physiological function and pathological significance of Nox4. As Nox4
      might serve as a potential target for the therapy of cardiovascular diseases and
      cancer, the Nox4 inhibitor is also discussed in this article. 

PMID- 25950601
TI  - Evaluation of a metalloporphyrin (THPPMnCl) for necrosis-affinity in rat models
      of necrosis.
AB  - The combination of an (13I)I-labeled necrosis-targeting agent (NTA) with a
      vascular disrupting agent is a novel and potentially powerful technique for tumor
      necrosis treatment (TNT). The purpose of this study was to evaluate a NTA
      candidate, THPPMnCl, using (131)I isotope for tracing its biodistribution and
      necrosis affinity. (131)I-THPPMnCl was intravenously injected in rat models with
      liver, muscle, and tumor necrosis and myocardial infarction (MI), followed by
      investigations with macroscopic autoradiography, triphenyltetrazolium chloride
      (TTC) histochemical staining, fluorescence microscopy and H&E stained histology
      for up to 9 days. (131)I-THPPMnCl displayed a long-term affinity for all types of
      necrosis and accumulation in the mononuclear phagocytic system especially in the
      liver. Autoradiograms and TTC staining showed a good targetability of (131)I
      THPPMnCl for MI. These findings indicate the potential of THPPMnCl for non
      invasive imaging assessment of necrosis, such as in MI. However, (13I)I-THPPMnCl
      is unlikely suitable for TNT due to its long-term retention in normal tissues. 

PMID- 25950602
TI  - Paediatric drug development of ramipril: reformulation, in vitro and in vivo
      evaluation.
AB  - Ramipril is used mainly for the treatment of hypertension and to reduce incidence
      of fatality following heart attacks in patients who develop indications of
      congestive heart failure. In the paediatric population, it is used most commonly
      for the treatment of heart failure, hypertension in type 1 diabetes and diabetic
      nephropathy. Due to the lack of a suitable liquid formulation, the current study
      evaluates the development of a range of oral liquid formulations of ramipril
      along with their in vitro and in vivo absorption studies. Three different
      formulation development approaches were studied: solubilisation using acetic acid
      as a co-solvent, complexation with hydroxypropyl-beta-cyclodextrin (HP-beta-CD)
      and suspension development using xanthan gum. Systematic optimisation of
      formulation parameters for the different strategies resulted in the development
      of products stable for 12 months at long-term stability conditions. In vivo
      evaluation showed C(max) of 10.48 ug/ml for co-solvent, 13.04 ug/ml for the
      suspension and 29.58 ug/ml for the cyclodextrin-based ramipril solution.
      Interestingly, both ramipril solution (co-solvent) and the suspension showed a
      T(max) of 2.5 h, however, cyclodextrin-based ramipril produced T(max) at 0.75 h
      following administration. The results presented in this study provide
      translatable products for oral liquid ramipril which offer preferential
      paediatric use over existing alternatives.

PMID- 25950603
TI  - Aptamers: new arrows to target dendritic cells.
AB  - Aptamers, as a novel class of molecular probes for diagnosis, imaging and
      targeting therapy, have attracted increasing attention in recent years. Aptamers
      are generated from libraries of single-stranded nucleic acids against different
      molecules via the "systematic evolution of ligands by exponential enrichment"
      (SELEX) method. SELEX is a repetitive process of a sequential selection procedure
      in which a DNA or RNA library pool is incubated separately with target and
      control molecules to select specific oligonucleotide aptamers with high
      affinities and specificities. Cell-SELEX is a modified version of the SELEX
      process in which whole living cells are used as targets for the aptamers.
      Dendritic cell (DC) targeting, as a new therapeutic approach, can improve the
      efficiency of immunotherapy in the treatment of allergies and cancers. DCs use
      various receptors to continuously induce adaptive immunity via capture and
      presentation of antigens to naive T cells. DCs are considered as the best targets
      in modulating immune responses against cancer, autoimmunity, allergy and
      transplantation. Aptamers, as a new agent, can be applied in DC targeting. The
      purpose of this review is to present some general concepts of aptamer production
      and DC targeting by aptamer molecules. 

PMID- 25950604
TI  - Ca-mediated electroformation of cell-sized lipid vesicles.
AB  - Cell-sized lipid giant unilamellar vesicles (GUVs) are formed when lipid
      molecules self-assemble to construct a single bilayer compartment with similar
      morphology to living cells. The physics of self-assembly process is only
      generally understood and the size distribution of GUVs tends to be very
      polydisperse. Herein we report a strategy for the production of controlled size
      distributions of GUVs by a novel mechanism dissecting the mediation ability of
      calcium (Ca) on the conventional electroformation of GUVs. We finely construct
      both of the calcium ion (Ca(2+)) and calcium carbonate (CaCO3) mineral adsorption
      layers on a lipid film surface respectively during the electroformation of GUVs.
      It is found that Ca(2+) Slip plane polarized by alternating electric field could
      induce a pattern of electroosmotic flow across the surface, and thus confine the
      fusion and growth of GUVs to facilitate the formation of uniform GUVs. The model
      is further improved by directly using CaCO3 that is in situ formed on a lipid
      film surface, providing a GUV population with narrow polydispersity. The two
      models deciphers the new biological function of calcium on the birth of cell-like
      lipid vesicles, and thus might be potentially relevant to the construction of new
      model to elucidate the cellular development process. 

PMID- 25950605
TI  - Effect of metabolic syndrome on mitsugumin 53 expression and function.
AB  - Metabolic syndrome is a cluster of risk factors, such as obesity, insulin
      resistance, and hyperlipidemia that increases the individual's likelihood of
      developing cardiovascular diseases. Patients inflicted with metabolic disorders
      also suffer from tissue repair defect. Mitsugumin 53 (MG53) is a protein
      essential to cellular membrane repair. It facilitates the nucleation of
      intracellular vesicles to sites of membrane disruption to create repair patches,
      contributing to the regenerative capacity of skeletal and cardiac muscle tissues
      upon injury. Since individuals suffering from metabolic syndrome possess tissue
      regeneration deficiency and MG53 plays a crucial role in restoring membrane
      integrity, we studied MG53 activity in mice models exhibiting metabolic disorders
      induced by a 6 month high-fat diet (HFD) feeding. Western blotting showed that
      MG53 expression is not altered within the skeletal and cardiac muscles of mice
      with metabolic syndrome. Rather, we found that MG53 levels in blood circulation
      were actually reduced. This data directly contradicts findings presented by Song
      et. al that indict MG53 as a causative factor for metabolic syndrome (Nature 494,
      375-379). The diminished MG53 serum level observed may contribute to the
      inadequate tissue repair aptitude exhibited by diabetic patients. Furthermore,
      immunohistochemical analyses reveal that skeletal muscle fibers of mice with
      metabolic disorders experience localization of subcellular MG53 around
      mitochondria. This clustering may represent an adaptive response to oxidative
      stress resulting from HFD feeding and may implicate MG53 as a guardian to protect
      damaged mitochondria. Therapeutic approaches that elevate MG53 expression in
      serum circulation may be a novel method to treat the degenerative tissue repair
      function of diabetic patients. 

PMID- 25950607
TI  - Teaching retirement financial literacy in an undergraduate gerontology classroom:
      broadening the concept of the tripod or three-legged stool of retirement income
      utilizing active learning.
AB  - The three-legged stool concept is widely used in gerontological and geriatric
      education as an explanation on how one should fiscally approach his or her
      retirement. Financial managers, planners, retirees, business owners, even the
      Social Security Administration uses this metaphor of fiscal soundness in
      retirement planning. Gerontologists are moving away from the "tripod of
      retirement income" and "three-legged stool" term, as more often market work is
      needed for financial security. This activity focuses on the tripod or three
      legged stool concepts of retirement planning using active learning, allowing the
      students to work collaboratively in a group, reflect upon the activity, and most
      importantly have fun. The game also allows for an expansion of the tripod
      concepts into the four pillars of economic security, broaching the use of
      personal assets and the possible need for longer employment. Game scenarios also
      emphasize macro- and microlevel forces, such as race, gender, health status,
      education, or marital status, which can influence timing of retirement or the
      level of retirement income available. The authors include instructions on how to
      set up the learning experience including worksheets, as well as reflection
      questions posed throughout the process. 

PMID- 25950606
TI  - A TSHbeta Variant with Impaired Immunoreactivity but Intact Biological Activity
      and Its Clinical Implications.
AB  - BACKGROUND: Thyrotropin (TSH) deficiency caused by TSHbeta gene mutations is a
      rare form of congenital central hypothyroidism. Nine different TSHbeta gene
      mutations have been reported, all with clinical manifestations. The aim was to
      identify the genetic cause of undetectable TSH levels in two siblings with
      clinical euthyroidism. METHODS: Two brothers born to consanguineous Pakistani
      parents presented with undetectable serum TSH but normal iodothyronine
      concentrations and no clinical signs of hypothyroidism. Direct sequencing of the
      TSHbeta gene, functional and immunological studies, protein homology modeling,
      and population frequency analysis were performed to characterize the cause of
      undetectable TSH in this family. RESULTS: Direct sequencing of the TSHbeta gene
      revealed that the two brothers were homozygous for a single nucleotide
      substitution (c.223A>G) resulting in the replacement of arginine 55 with glycine
      (R55G). This variant was found in 12 out of 5008 alleles in the 1000 Genomes
      project (all South Asian). Serum TSH of the two brothers was undetectable in two
      of five platforms, both produced by Siemens, whereas TSH levels of the
      heterozygous brother and mother were half compared to the other three platforms
      (Roche Elecsys, Abbott Architect, and Beckman Coulter DxI). The falsely low TSH
      concentration was caused by the monoclonal antibody not recognizing the region
      containing the variant amino acid. This is supported by the fact that arginine
      modification--following phenylglyoxal treatment--led to a significant (96%)
      decrease in the TSH measurement with the Siemens platforms. Predictions based on
      PolyPhen-2 and in silico modeling revealed no functional impairment of the
      variant TSH. CONCLUSIONS: A TSHbeta variant with impaired immunoreactivity, but
      not bioactivity, is reported, and its biochemical impact in the homo- and
      heterozygous state is demonstrated. It is also shown that failure to bind to the
      monoclonal antibody is a direct consequence of the amino acid substitution.

PMID- 25950608
TI  - Metastatic breast cancer cells in lymph nodes increase nodal collagen density.
AB  - The most life-threatening aspect of breast cancer is the occurrence of metastatic
      disease. The tumor draining lymph nodes typically are the first sites of
      metastasis in breast cancer. Collagen I fibers and the extracellular matrix have
      been implicated in breast cancer to form avenues for metastasis. In this study,
      we have investigated extracellular matrix molecules such as collagen I fibers in
      the lymph nodes of mice bearing orthotopic human breast cancer xenografts. The
      lymph nodes in mice with metastatic MDA-MB-231 and SUM159 tumor xenografts and
      tumor xenografts grown from circulating tumor cell lines displayed an increased
      collagen I density compared to mice with no tumor and mice with non-metastatic T
      47D and MCF-7 tumor xenografts. These results suggest that cancer cells that have
      metastasized to the lymph nodes can modify the extracellular matrix components of
      these lymph nodes. Clinically, collagen density in the lymph nodes may be a good
      marker for identifying lymph nodes that have been invaded by breast cancer cells.

PMID- 25950609
TI  - Association between BDNF gene polymorphisms and attention deficit hyperactivity
      disorder in Korean children.
AB  - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a common childhood
      neuropsychiatric disorder characterized by behavioral problems such as attention
      deficit, hyperactivity, and impulsivity. The brain-derived neurotrophic factor
      (BDNF) is the most abundant neurotrophin in the brain. AIMS: The aim of the
      present study was to investigate the association between the genotype and alleles
      for the BDNF gene in Korean children with ADHD. METHODS: The sample consisted of
      180 ADHD children and 159 control children. We diagnosed ADHD according to the
      DSM-IV. ADHD symptoms were evaluated with Conners' Parent Rating Scales and
      Dupaul Parent ADHD Rating Scales. Blood samples were taken from the 339 subjects,
      DNA was extracted from blood lymphocytes, and polymerase chain reaction was
      performed for BDNF rs6265, rs11030101, rs10835210, rs7103873, and rs2030324
      polymorphisms. Alleles and genotype frequencies were compared using the Chi
      square test. We compared the allele and genotype frequencies of the BDNF gene
      polymorphism in the ADHD and control groups. RESULTS: This study showed that
      there was a significant correlation among the allele frequencies of the
      rs11030101 and rs10835210 single nucleotide polymorphisms (SNPs) (odds
      ratio=0.61, 95% confidence interval=0.39-0.96, p=0.034), but the final
      conclusions are not definite. Follow-up studies with larger patient or pure
      subgroups are expected. These results suggest that the BDNF allelic structure may
      impact ADHD symptoms.

PMID- 25950610
TI  - A versatile clearing agent for multi-modal brain imaging.
AB  - Extensive mapping of neuronal connections in the central nervous system requires
      high-throughput um-scale imaging of large volumes. In recent years, different
      approaches have been developed to overcome the limitations due to tissue light
      scattering. These methods are generally developed to improve the performance of a
      specific imaging modality, thus limiting comprehensive neuroanatomical
      exploration by multi-modal optical techniques. Here, we introduce a versatile
      brain clearing agent (2,2'-thiodiethanol; TDE) suitable for various applications
      and imaging techniques. TDE is cost-efficient, water-soluble and low-viscous and,
      more importantly, it preserves fluorescence, is compatible with immunostaining
      and does not cause deformations at sub-cellular level. We demonstrate the
      effectiveness of this method in different applications: in fixed samples by
      imaging a whole mouse hippocampus with serial two-photon tomography; in
      combination with CLARITY by reconstructing an entire mouse brain with light sheet
      microscopy and in translational research by imaging immunostained human
      dysplastic brain tissue. 

PMID- 25950611
TI  - Chest Wall Resection for Single Rib Metastasis after Breast Cancer.

PMID- 25950612
TI  - Microangiographic Comparison of the Effects of 3 Loop Pulley and 6 Strand Savage
      Tenorrhaphy Techniques on Equine Superficial Digital Flexor Tendon.
AB  - OBJECTIVE: The 6-strand Savage (SSS) tenorrhaphy pattern is biomechanically
      superior to the commonly employed 3-loop pulley (3LP); however, its effects on
      intrinsic tendon vasculature remain unknown. The objective of this study was to
      compare perfusion of intrinsic vasculature of the equine superficial digital
      flexor tendon (SDFT) after 3LP and SSS tenorrhaphies. We hypothesized that the
      SSS technique would significantly decrease vascular perfusion compared to the 3LP
      technique. STUDY DESIGN: Ex vivo, randomized, paired design. ANIMALS: Horses (n =
      9) METHODS: Under general anesthesia, 9 pairs of forelimb SDFT were transected.
      Two tendons served as baseline control, the remainder had either SSS or 3LP
      tenorrhaphy performed. Horses were heparinized, euthanatized, and forelimbs
      perfused with barium sulfate solution were then fixed with formalin under
      tension. Tendons were transected every 5 mm and microangiographic images
      obtained. Microvascular analysis of sections proximal to, throughout, and distal
      to the tenorrhaphy was completed using a custom macro. Differences in vascular
      count were assessed using MANOVA. RESULTS: A significant reduction in the number
      of perfused vessels was seen for SSS compared with 3LP at 2 locations within the
      tenorrhaphy (P = .039 and P = .009). The SSS technique took on average 4.7 +/-
      0.9 times longer to place. CONCLUSIONS: The SSS technique causes an acute
      reduction in tendon perfusion compared to the 3LP, which may limit its clinical
      use. Further research is required to elucidate the clinical significance of this
      difference.

PMID- 25950613
TI  - Meta-analysis of digital game and study characteristics eliciting physiological
      stress responses.
AB  - Digital games have been used as stressors in a range of disciplines for decades.
      Nonetheless, the underlying characteristics of these stressors and the study in
      which the stressor was applied are generally not recognized for their moderating
      effect on the measured physiological stress responses. We have therefore
      conducted a meta-analysis that analyzes the effects of characteristics of digital
      game stressors and study design on heart rate, systolic and diastolic blood
      pressure, in studies carried out from 1976 to 2012. In order to assess the
      differing quality between study designs, a new scale is developed and presented,
      coined reliability of effect size. The results show specific and consistent
      moderating functions of both game and study characteristics, on average
      accounting for around 43%, and in certain cases up to 57% of the variance found
      in physiological stress responses. Possible cognitive and physiological processes
      underlying these moderating functions are discussed, and a new model integrating
      these processes with the moderating functions is presented. These findings
      indicate that a digital game stressor does not act as a stressor by virtue of
      being a game, but rather derives its stressor function from its characteristics
      and the methodology in which it is used. This finding, together with the size of
      the associated moderations, indicates the need for a standardization of digital
      game stressors. 

PMID- 25950614
TI  - The effect of hydrogen ordering on the electronic and magnetic properties of the
      strontium vanadium oxyhydride.
AB  - The electronic and magnetic properties of the recently fabricated strontium
      vanadium perovskite oxyhydride are investigated by ab initio calculations. The
      role of the unusually ordered hydrogen ions are carefully analyzed. The hydrogen
      ions break the crystal symmetry to change the degeneracy of the V t(2g) orbit,
      thus inducing magnetic transitions from the paramagnetism of parent oxides to the
      antiferromagnetism of oxyhydride. The low dimension behaviors would been expected
      because of the nonbonding nature between the V t(2g) and H s orbitals due to
      symmetry. Moreover, our results indicate that the direct hoppings of the nearest
      neighboring two V t(2g) orbitals and the indirect hoppings mediated by Sr ions
      should be essential to understanding the electronic and magnetic properties of
      the perovskite oxyhydride.

PMID- 25950615
TI  - Weighing up the benefits and harms of a new anti-cancer drug: a survey of
      Australian oncologists.
AB  - BACKGROUND: Little is known about the relative importance that oncologists
      attribute to the benefits and harms of anti-cancer drugs when considering
      treatment options with their patients. AIM: To quantify the trade-offs made
      between overall survival, progression-free survival and adverse effects. METHODS:
      A web-based survey elicited importance weights for the benefits and harms of
      bevacizumab or everolimus. Combining the importance weights with trial-based
      probabilities produced a score and ranking for each treatment option. RESULTS: A
      total of 40 responses was received for the bevacizumab scenario and 32 for the
      everolimus scenario. All respondents regarded overall survival and progression
      free survival as the most important attributes - more important than avoiding the
      potential harms regardless of drugs. Among the potential harms, respondents
      allocated the highest mean importance weight to gastrointestinal (GI) perforation
      and rated absolute improvement in overall survival as 1.6 times and 2.3 times as
      important as avoiding GI perforation in the two versions of the bevacizumab
      scenario respectively. For the everolimus scenario, stomatitis and pneumonitis
      were allocated the highest mean importance weights with absolute improvement in
      overall survival rated as 2.2 times as important as avoiding
      stomatitis/pneumonitis. All 40 respondents (100%) favoured treatment option with
      bevacizumab to no bevacizumab based on respondents' determined weights for
      treatment attributes. The converse was found for everolimus with 22 (69%) of
      respondents preferring the 'no everolimus' option. CONCLUSION: Oncologists'
      preferences over the benefits and harms of treatment do, when combined with
      evidence of effect, influence treatment decisions for anti-cancer drugs.

PMID- 25950616
TI  - Outer retinal changes in endoilluminator-induced phototoxic maculopathy evident
      on spectral-domain optical coherence tomography.

PMID- 25950617
TI  - 2DL1, 2DL2 and 2DL3 all contribute to KIR phenotype variability on human NK
      cells.
AB  - Natural killer (NK) cells are lymphocytes that function as part of the innate
      immune system. Their activity is controlled by a range of inhibitory and
      activating receptors, including the important killer-cell immunoglobulin-like
      receptors (KIR). The KIR are a multi-gene family of receptors that interact with
      the human leukocyte antigen (HLA) class I family of molecules and are
      characterised by extensive allelic polymorphism. Their expression on the cell
      surface of NK cells is highly variable, but the factors responsible for this
      variability are not yet clearly understood. In the current study, we investigated
      KIR expression in a healthy human cohort that we had previously characterised in
      depth at a genetic level, with KIR allele typing and HLA class I ligand genotypes
      available for all donors (n=198). Allelic polymorphism significantly affected the
      phenotypic expression of all KIR analysed, whereas HLA ligand background
      influenced the expression levels of 2DL1 and 2DL3. In particular, we found that
      although 2DL2 may influence 2DL1 expression, this appears to be owing to
      variation in 2DL1 copy number. Finally, the inhibitory receptor LILRB1 had higher
      expression levels in individuals with B/B KIR genotypes, suggesting a possible
      relationship between KIR and non-KIR receptors, which serves to balance NK cell
      activation potential. 

PMID- 25950618
TI  - Adolescent alcohol exposure decreased sensitivity to nicotine in adult Wistar
      rats.
AB  - Many adolescents engage in heavy alcohol use. Limited research in humans
      indicates that adolescent alcohol use predicts adult tobacco use. The present
      study investigated whether adolescent intermittent ethanol (AIE) exposure alters
      nicotine sensitivity in adulthood. Adolescent male Wistar rats (postnatal day 28
      53) were exposed to AIE exposure that consisted of 5 g/kg of 25 percent ethanol
      three times per day in a 2 days on/2 days off regimen. Control rats received
      water with the same exposure regimen. In adulthood, separate groups of rats were
      tested for nicotine intravenous self-administration (IVSA), drug discrimination
      and conditioned taste aversion (CTA). The dose-response function for nicotine
      IVSA under a fixed-ratio schedule of reinforcement was similar in AIE-exposed and
      control rats. However, AIE-exposed rats self-administered less nicotine at the
      lowest dose, suggesting that low-dose nicotine was less reinforcing in AIE
      exposed, compared with control rats. AIE-exposed rats self-administered less
      nicotine under a progressive-ratio schedule, suggesting decreased motivation for
      nicotine after AIE exposure. The discriminative stimulus effects of nicotine were
      diminished in AIE-exposed rats compared with control rats. No group differences
      in nicotine CTA were observed, suggesting that AIE exposure had no effect on the
      aversive properties of nicotine. Altogether, these results demonstrate that AIE
      exposure decreases sensitivity to the reinforcing, motivational and
      discriminative properties of nicotine while leaving the aversive properties of
      nicotine unaltered in adult rats. These findings suggest that drinking during
      adolescence may result in decreased sensitivity to nicotine in adult humans,
      which may in turn contribute to the higher rates of tobacco smoking.

PMID- 25950619
TI  - Laparoscopy-assisted transduodenal excision of superficial non-ampullary duodenal
      epithelial tumors.
AB  - INTRODUCTION: Transduodenal excision (transduodenal submucosal dissection) is an
      alternative to pancreaticoduodenectomy for the treatment of benign and low-grade
      malignant tumors of the duodenum. However, laparoscopic transduodenal excision or
      laparoscopy-assisted transduodenal excision (LATDE) of such tumors has been
      rarely reported. In this paper, we present the preliminary results of LATDE in
      patients with superficial non-ampullary duodenal epithelial tumors. METHODS:
      Three patients with superficial non-ampullary duodenal epithelial tumors (mucosal
      adenocarcinoma, n = 1; tubular adenoma, n = 2) underwent LATDE. LATDE consists of
      four major procedures: (i) laparoscopic wide Kocher maneuver (mobilization of the
      pancreaticoduodenum); (ii) extracorporeal approach to the fully mobilized
      duodenum through the upper median longitudinal incision (4 cm in length); (iii)
      tumor excision by submucosal dissection under direct vision through longitudinal
      duodenotomy (4 cm in length); and (iv) hand-sewn closure of the mucosal defect
      and duodenotomy. RESULTS: LATDE was successfully carried out without any
      intraoperative or postoperative adverse events. The mean operating time and
      estimated blood loss were 155 min and 17 mL, respectively. Contrast
      roentgenography on postoperative day 4 showed neither duodenal deformity nor
      disturbance of gastroduodenal emptying in any of the patients. CONCLUSIONS: LATDE
      could eliminate the possibility of peritoneal or port-site seeding of tumor cells
      because the duodenotomy and tumor excision are performed extracorporeally. The
      meticulously hand-sewn closures of the mucosal defect and duodenotomy can
      minimize the possibility of postoperative hemorrhage and/or anastomotic leakage.
      LATDE is a feasible, safe, and minimally invasive treatment for patients with
      superficial non-ampullary duodenal epithelial tumors that have no risk of lymph
      node metastasis in the first and second portions of the duodenum.

PMID- 25950620
TI  - Accurate computation of survival statistics in genome-wide studies.
AB  - A key challenge in genomics is to identify genetic variants that distinguish
      patients with different survival time following diagnosis or treatment. While the
      log-rank test is widely used for this purpose, nearly all implementations of the
      log-rank test rely on an asymptotic approximation that is not appropriate in many
      genomics applications. This is because: the two populations determined by a
      genetic variant may have very different sizes; and the evaluation of many
      possible variants demands highly accurate computation of very small p-values. We
      demonstrate this problem for cancer genomics data where the standard log-rank
      test leads to many false positive associations between somatic mutations and
      survival time. We develop and analyze a novel algorithm, Exact Log-rank Test
      (ExaLT), that accurately computes the p-value of the log-rank statistic under an
      exact distribution that is appropriate for any size populations. We demonstrate
      the advantages of ExaLT on data from published cancer genomics studies, finding
      significant differences from the reported p-values. We analyze somatic mutations
      in six cancer types from The Cancer Genome Atlas (TCGA), finding mutations with
      known association to survival as well as several novel associations. In contrast,
      standard implementations of the log-rank test report dozens-hundreds of likely
      false positive associations as more significant than these known associations. 

PMID- 25950622
TI  - Neuroaxonal dystrophy in PLA2G6 knockout mice.
AB  - The PLA2G6 gene encodes group VIA calcium-independent phospholipase A2 (iPLA2
      beta), which belongs to the PLA2 superfamily that hydrolyses the sn-2 ester bond
      in phospholipids. In the nervous system, iPLA2 beta is essential for remodeling
      membrane phospholipids in axons and synapses. Mutated PLA2G6 causes PLA2G6
      associated neurodegeneration (PLAN) including infantile neuroaxonal dystrophy
      (INAD) and adult-onset dystonia-parkinsonism (PARK14), which have unique clinical
      phenotypes. In the PLA2G6 knockout (KO) mouse, which is an excellent PLAN model,
      specific membrane degeneration takes place in neurons and their axons, and this
      is followed by axonal spheroid formation. These pathological findings are similar
      to those in PLAN. This review details the evidence that membrane degeneration of
      mitochondria and axon terminals is a precursor to spheroid formation in this
      disease model. From a young age before the onset, many mitochondria with damaged
      inner membranes appear in PLA2G6 KO mouse neurons. These injured mitochondria
      move anterogradely within the axons, increasing in the distal axons. As membrane
      degeneration progresses, the collapse of the double membrane of mitochondria
      accompanies axonal injury near impaired mitochondria. At the axon terminals, the
      membranes of the presynapses expand irregularly from a young age. Over time, the
      presynaptic membrane ruptures, causing axon terminal degeneration. Although these
      processes occur in different degenerating membranes, both contain tubulovesicular
      structures, which are a specific ultrastructural marker of INAD. This indicates
      that two unique types of membrane degeneration underlie PLAN pathology. We have
      shown a new pathological mechanism whereby axons degenerate due to defective
      maintenance and rupture of both the inner mitochondrial and presynaptic
      membranes. This degeneration mechanism could possibly clarify the pathologies of
      PLAN, Parkinson disease and neurodegeneration with iron accumulation (NBIA),
      which are assumed to be due to the primary degeneration of axons. 

PMID- 25950623
TI  - Two Jungs. Apropos a paper by Mark Saban.
AB  - Jung's idea of the 'personal equation' amounts to the reflection that theoretical
      differences between the psychologies that people teach are rooted in their
      personalities, in other words, that they are due to the psychology each one
      'has'. This concept also applies to different interpretations of Jung's work. The
      serious difficulties that Mark Saban has with my psychology are a case in point.
      Recourse to the concept of the personal equation reveals that Saban has his Jung
      and I have mine. With his insistence on his Talmudic methodological principle of
      dream interpretation, that 'the dream is its own interpretation', according to
      Saban Jung means nothing but a rejection of Freudian free association. My Jung
      goes far beyond that. Jung understands this methodological principle above all in
      terms of what he calls 'circumambulation'. The main part of this paper is devoted
      to an elucidation of what circumambulation involves as a mode of dream
      interpretation. The paper concludes with the distinction Jung himself introduced
      between two types of reading of his work, either as 'paper' and 'dead nostrums'
      or as 'fire and wind', and pleads for a reconstruction of Jung's psychology as a
      whole in terms of his most advanced, deepest insights, instead of a dogmatic
      reading mainly based on the early Jung, a reading for which his later
      revolutionary insights are at best negligible embellishments. 

PMID- 25950621
TI  - Peri-operative management of the obese surgical patient 2015: Association of
      Anaesthetists of Great Britain and Ireland Society for Obesity and Bariatric
      Anaesthesia.
AB  - Guidelines are presented for the organisational and clinical peri-operative
      management of anaesthesia and surgery for patients who are obese, along with a
      summary of the problems that obesity may cause peri-operatively. The advice
      presented is based on previously published advice, clinical studies and expert
      opinion. 

PMID- 25950624
TI  - Copper removal using electrosterically stabilized nanocrystalline cellulose.
AB  - Removal of heavy metal ions such as copper using an efficient and low-cost method
      with low ecological footprint is a critical process in wastewater treatment,
      which can be achieved in a liquid phase using nanoadsorbents such as inorganic
      nanoparticles. Recently, attention has turned toward developing sustainable and
      environmentally friendly nanoadsorbents to remove heavy metal ions from aqueous
      media. Electrosterically stabilized nanocrystalline cellulose (ENCC), which can
      be prepared from wood fibers through periodate/chlorite oxidation, has been shown
      to have a high charge content and colloidal stability. Here, we show that ENCC
      scavenges copper ions by different mechanisms depending on the ion concentration.
      When the Cu(II) concentration is low (C0?200 ppm), agglomerates of starlike ENCC
      particles appear, which are broken into individual starlike entities by shear and
      Brownian motion, as evidenced by photometric dispersion analysis, dynamic light
      scattering, and transmission electron microscopy. On the other hand, at higher
      copper concentrations, the aggregate morphology changes from starlike to
      raftlike, which is probably due to the collapse of protruding dicarboxylic
      cellulose (DCC) chains and ENCC charge neutralization by copper adsorption. Such
      raftlike structures result from head-to-head and lateral aggregation of
      neutralized ENCCs as confirmed by transmission electron microscopy. As opposed to
      starlike aggregates, the raftlike structures grow gradually and are prone to
      sedimentation at copper concentrations C0?500 ppm, which eliminates a costly
      separation step in wastewater treatment processes. Moreover, a copper removal
      capacity of ~185 mg g(-1) was achieved thanks to the highly charged DCC
      polyanions protruding from ENCC. These properties along with the biorenewability
      make ENCC a promising candidate for wastewater treatment, in which fast, facile,
      and low-cost removal of heavy metal ions is desired most.

PMID- 25950625
TI  - Enabling photoperiodic control of flowering by timely chromatin silencing of the
      florigen gene.
AB  - Many plants synchronize their flowering times with changing seasons to maximize
      reproductive success. A key seasonal cue is the change in day length
      (photoperiod), that induces the production of a systemic flowering signaling
      molecule called florigen. A major florigen component is FLOWERING LOCUS T (FT) or
      its orthologs. In the long-day plant Arabidopsis thaliana, FT expression is well
      known to be activated by the photoperiod pathway output specifically near dusk in
      long days; however, underappreciated is the importance of FT silencing at other
      times of the day, in enabling Arabidopsis to respond only to long days in
      flowering. We have recently reported that a plant-specific chromatin-silencing
      complex called EMF1c represses FT expression at times other than around dusk in
      long days to prevent its temporal ectopic expression from "spoiling" the long-day
      floral induction in Arabidopsis. Here I further discuss in other day-length
      sensitive plants the potential involvement of a chromatin mechanism similar to
      the Arabidopsis EMF1c-mediated silencing, in repressing the expression of FT
      orthologs to enable diverse photoperiodic control of flowering. 

PMID- 25950626
TI  - Lights on for the molecular players of presynaptic plasticity.
AB  - Neuronal response or adaption to a changing environment relies on the modulation
      of synaptic function. How this modulation is achieved remains controversial. In
      this issue of Neuron, Sugie et al. (2015) now report that active zones of
      Drosophila photoreceptors undergo activity-dependent changes in their molecular
      composition.

PMID- 25950627
TI  - Dissecting the dynamics of corticothalamic feedback.
AB  - The thalamus and neocortex are intimately interconnected via a reciprocal
      arrangement of feedforward and feedback projections. In this issue of Neuron,
      Crandall et al. (2015) provide key insight into the functional dynamics of
      feedback projections and reveal the cellular and circuit mechanisms that underlie
      a rate-dependent switch in the net influence, suppression versus excitation, that
      cortex can exert on thalamic relay cells.

PMID- 25950628
TI  - How cumulative error in grid cell firing is literally bounded by the environment.
AB  - In this issue of Neuron, Hardcastle et al. (2015) show that the spatial firing
      patterns of grid cells accumulate error, drifting coherently, until reset by
      encounters with environmental boundaries. These results reveal important aspects
      of the neural dynamics of self-localization from self-motion and environmental
      information.

PMID- 25950629
TI  - A multilayered story of memory retrieval.
AB  - The successful retrieval of learned visual associations requires coordination of
      multiple brain regions involved in the encoding and association of visual images.
      In this issue of Neuron, Takeda et al. (2015) use a combination of modern
      recording and analytical methods to eavesdrop on this process.

PMID- 25950630
TI  - The Hitchhiker's Guide to a Neuroscience Career.
AB  - Neuroscience is an exciting and vibrant field, but building an academic career is
      not always easy. What are critical success indicators? Which tools help talented
      young neuroscientists conquer the challenges? In this NeuroView, we discuss
      instruments and steps that can help people progress through the ranks. 

PMID- 25950632
TI  - Amyloid polymorphism: structural basis and neurobiological relevance.
AB  - Our understanding of the molecular structures of amyloid fibrils that are
      associated with neurodegenerative diseases, of mechanisms by which disease
      associated peptides and proteins aggregate into fibrils, and of structural
      properties of aggregation intermediates has advanced considerably in recent
      years. Detailed molecular structural models for certain fibrils and aggregation
      intermediates are now available. It is now well established that amyloid fibrils
      are generally polymorphic at the molecular level, with a given peptide or protein
      being capable of forming a variety of distinct, self-propagating fibril
      structures. Recent results from structural studies and from studies involving
      cell cultures, transgenic animals, and human tissue provide initial evidence that
      molecular structural variations in amyloid fibrils and related aggregates may
      correlate with or even produce variations in disease development. This article
      reviews our current knowledge of the structural and mechanistic aspects of
      amyloid formation, as well as current evidence for the biological relevance of
      structural variations. 

PMID- 25950635
TI  - Tuning zinc(II) coordination architectures by rigid long bis(triazole) and
      different carboxylates: Synthesis, structures and fluorescence properties.
AB  - Three metal-organic coordination polymers containing rigid bis(triazole) ligand,
      namely, [Zn1.5(btb)(nbta)(H2O)]n (1), {[Zn(btb)(3-nph)].(H2O)}n (2) and
      [Zn(btb)(4-nph)]n (3) (btb=4,4'-bis(1,2,4-triazolyl-1-yl)-biphenyl, 3-H2nph=3
      nitrophthalic acid, H3nbta=5-nitro-1,2,3-benzenetricarboxylic acid, and 4-H2nph=4
      nitrophthalic acid) were synthesized under hydrothermal conditions and
      structurally characterized by X-ray single-crystal diffraction. Complex 1
      possesses an interesting 3D coordination framework with a rarely binodal (4,4)
      connected frl topological structure. Complexes 2 and 3 exhibit similiar 2D (4,4)
      grid layers with different point symbol (4(4).6(4)) in 2 and (4(4).6(2)) in 3.
      Furthermore, thermal stability of these compounds has been discussed. Complexes 1
      3 exhibit strong solid-state fluorescence at room temperature in solid state. 

PMID- 25950634
TI  - TRP Channels in Insect Stretch Receptors as Insecticide Targets.
AB  - Defining the molecular targets of insecticides is crucial for assessing their
      selectivity and potential impact on environment and health. Two commercial
      insecticides are now shown to target a transient receptor potential (TRP) ion
      channel complex that is unique to insect stretch receptor cells. Pymetrozine and
      pyrifluquinazon disturbed Drosophila coordination and hearing by acting on
      chordotonal stretch receptor neurons. This action required the two TRPs Nanchung
      (Nan) and Inactive (Iav), which co-occur exclusively within these cells. Nan and
      Iav together sufficed to confer cellular insecticide responses in vivo and in
      vitro, and the two insecticides were identified as specific agonists of Nan-Iav
      complexes that, by promoting cellular calcium influx, silence the stretch
      receptor cells. This establishes TRPs as insecticide targets and defines specific
      agonists of insect TRPs. It also shows that TRPs can render insecticides cell
      type selective and puts forward TRP targets to reduce side effects on non-target
      species.

PMID- 25950631
TI  - Brains, genes, and primates.
AB  - One of the great strengths of the mouse model is the wide array of genetic tools
      that have been developed. Striking examples include methods for directed
      modification of the genome, and for regulated expression or inactivation of
      genes. Within neuroscience, it is now routine to express reporter genes, neuronal
      activity indicators, and opsins in specific neuronal types in the mouse. However,
      there are considerable anatomical, physiological, cognitive, and behavioral
      differences between the mouse and the human that, in some areas of inquiry, limit
      the degree to which insights derived from the mouse can be applied to
      understanding human neurobiology. Several recent advances have now brought into
      reach the goal of applying these tools to understanding the primate brain. Here
      we describe these advances, consider their potential to advance our understanding
      of the human brain and brain disorders, discuss bioethical considerations, and
      describe what will be needed to move forward. 

PMID- 25950636
TI  - Study on the interaction between Besifloxacin and bovine serum albumin by
      spectroscopic techniques.
AB  - The interaction between Besifloxacin (BFLX) and bovine serum albumin (BSA) was
      investigated by spectroscopic (fluorescence, UV-Vis absorption and circular
      dichroism) techniques under imitated physiological conditions. The experiments
      were conducted at different temperatures (298, 304 and 310 K) and the results
      showed that the BFLX caused the fluorescence quenching of BSA through a static
      quenching procedure. The binding constant (Ka), binding sites (n) were obtained.
      The corresponding thermodynamic parameters (DeltaH, DeltaS and DeltaG) of the
      interaction system were calculated at different temperatures. The results
      revealed that the binding process was spontaneous and the acting force between
      BFLX and BSA were mainly electrostatic forces. According to Forster non-radiation
      energy transfer theory, the binding distance between BFLX and BSA was calculated
      to be 4.96 nm. What is more, both synchronous fluorescence and circular dichroism
      spectra confirmed conformational changes of BSA.

PMID- 25950638
TI  - Influence of homo buffer layer thickness on the quality of ZnO epilayers.
AB  - ZnO buffer layers with different thicknesses were deposited on a-plane sapphire
      substrates at 300  degrees C. ZnO epilayers were grown on ZnO buffers at 600 
      degrees C by radio-frequency magnetron sputtering and vacuum annealed at 900 
      degrees C for an hour. Influence of nucleation layer thickness on the structural
      and quality of ZnO thin films was investigated using X-ray diffraction (XRD),
      atomic force microscopy (AFM), and Raman spectroscopy. The best ZnO film quality
      was obtained with the ZnO buffer layer of 45 nm thick which provided the
      smoothest surface with RMS value of 0.3 nm. X-ray diffraction measurements reveal
      that the films have a single phase wurtzite structure with (0001) preferred
      crystal orientation. As evident from narrow FWHM of ZnO (0002) rocking curve, ZnO
      buffer can serve as a good template for the growth of high-quality ZnO films with
      little tilt. In addition, the micro-Raman scattering measurements at room
      temperature revealed the existence of Raman active phonon modes of ZnO; A1(TO),
      A1(LO) and E2(high). The latter two modes were not observed in thin buffer layer
      beside the dis-appearance of E2(low) mode in all films.

PMID- 25950633
TI  - Pleasure systems in the brain.
AB  - Pleasure is mediated by well-developed mesocorticolimbic circuitry and serves
      adaptive functions. In affective disorders, anhedonia (lack of pleasure) or
      dysphoria (negative affect) can result from breakdowns of that hedonic system.
      Human neuroimaging studies indicate that surprisingly similar circuitry is
      activated by quite diverse pleasures, suggesting a common neural currency shared
      by all. Wanting for reward is generated by a large and distributed brain system.
      Liking, or pleasure itself, is generated by a smaller set of hedonic hot spots
      within limbic circuitry. Those hot spots also can be embedded in broader
      anatomical patterns of valence organization, such as in a keyboard pattern of
      nucleus accumbens generators for desire versus dread. In contrast, some of the
      best known textbook candidates for pleasure generators, including classic
      pleasure electrodes and the mesolimbic dopamine system, may not generate pleasure
      after all. These emerging insights into brain pleasure mechanisms may eventually
      facilitate better treatments for affective disorders. 

PMID- 25950637
TI  - Virgin silver nanoparticles as colorimetric nanoprobe for simultaneous detection
      of iodide and bromide ion in aqueous medium.
AB  - A simple colorimetric nanoprobe based on virgin silver nanoparticles (AgNPs) was
      developed for the selective detection of iodide and bromide ions via aggregation
      and anti-aggregation mechanism. With addition of I(-) ions, virgin AgNPs, in
      presence of Fe(3+), showed perceptible color change from yellow to colorless
      along with disappearance of surface plasmon resonance (SPR) band of AgNPs at 400
      nm. But in presence of Cr(3+), AgNPs turned yellow upon addition of I(-)and Br(-)
      anions. The developed virgin AgNPs probe showed high specificity and selectivity
      with the detection limits down to 0.32 MUM and 1.32 MUM for I(-) ions via two
      different mechanistic routes. Also, the designed probe detects Br(-) with a
      detection limit down to 1.67 MUM.

PMID- 25950639
TI  - Remote Stereoinduction in the Organocuprate-Mediated Allylic Alkylation of
      Allylic gem-Dichlorides: Highly Diastereoselective Synthesis of (Z)-Chloroalkene
      Dipeptide Isosteres.
AB  - Highly diastereoselective synthesis of (Z)-chloroalkene dipeptide isosteres has
      been achieved by 1,4-asymmetric induction in the organocuprate-mediated allylic
      alkylation adjacent to the chiral center of allylic gem-dichlorides. The reaction
      proceeds with a variety of heterocuprates prepared from CuCN and various
      organometallic reagents. It allows rapid construction of valuable architectures
      of L,D-type and L,L-type (Z)-chloroalkene dipeptide isosteres from the
      corresponding (E)- and (Z)-allylic gem-dichlorides in high yields, with excellent
      (Z)-selectivity and diastereoselectivity.

PMID- 25950640
TI  - Thematic issue: pharmacotherapy in sexual medicine: novel insights.

PMID- 25950641
TI  - Pathophysiology of erectile dysfunction.
AB  - Erectile dysfunction (ED) is a major health problem as the population ages. Basic
      science research for the last two decades has expanded the knowledge on ED and
      identified several key molecular changes associated with the pathogenesis of ED,
      including nitric oxide (NO) / cyclic guanosine monophosphate (cGMP) / protein
      kinase G (PKG) pathway, RhoA/Rho-associated protein kinase (ROCK) signaling
      pathway, reactive oxygen species (ROS), renin-angiotensin system (RAS) and tumor
      necrosis factor-alpha (TNF-alpha). The causes of ED are classified into aging,
      vasculogenic, neurogenic, endocrinological, drug-induced and psychogenic. ED is
      often associated with systemic diseases, such as diabetes and cardiovascular
      diseases. In this review, we will review the molecular mechanisms of ED and known
      mechanisms behind ED associated with systemic diseases. 

PMID- 25950642
TI  - Partnership in optimizing management of reflux symptoms: a treatment algorithm
      for over-the-counter proton-pump inhibitors.
AB  - BACKGROUND: Uncomplicated heartburn and acid regurgitation are increasingly
      treated and managed using over-the-counter medications. However, with over-the
      counter availability of antacids, alginates, histamine 2 receptor antagonists
      (H2RAs), and proton-pump inhibitors (PPIs), consumers need guidance as to
      appropriate options and how to use them. METHODS: Relevant guidelines, studies,
      and reviews were identified via literature searches of PubMed/Medline and Google
      Scholar, as well as cross-referencing from the identified papers. RESULTS:
      Antacids, alginates, and H2RAs are best suited to management of occasional
      heartburn, taken either before provocative meals or other triggers or on demand
      when symptoms arise. Over-the-counter PPIs are appropriate options across the
      range of symptom severity/frequency typically encountered in the pharmacy, but
      may be particularly appropriate for treatment of those with frequent and/or very
      bothersome heartburn. A 2-4 week course of daily PPIs can lead to complete
      resolution of frequent heartburn. Counseling is important to ensure that patients
      understand that failure of symptoms to resolve or a rapid return of symptoms
      while taking a PPI is an indication to consult a doctor, whereas a return of
      symptoms after a period of months may be an indication for just another course of
      treatment. The need for effective communication and for ensuring use of the
      correct medication in the over-the-counter setting puts much of the
      responsibility for management of heartburn and acid regurgitation on the
      pharmacist. A proposed algorithm that details when and how to use available over
      the-counter medications is presented. This algorithm also highlights alarm
      features and atypical symptoms indicative of other underlying conditions that
      should be referred directly to a physician. CONCLUSION: Implementation of a
      simple algorithm will empower pharmacists and consumers alike and ensure
      consistent and appropriate care.

PMID- 25950643
TI  - Tropospheric aqueous-phase chemistry: kinetics, mechanisms, and its coupling to a
      changing gas phase.

PMID- 25950644
TI  - Optimal spectral filtering in soliton self-frequency shift for deep-tissue
      multiphoton microscopy.
AB  - Tunable optical solitons generated by soliton self-frequency shift (SSFS) have
      become valuable tools for multiphoton microscopy (MPM). Recent progress in MPM
      using 1700 nm excitation enabled visualizing subcortical structures in mouse
      brain in vivo for the first time. Such an excitation source can be readily
      obtained by SSFS in a large effective-mode-area photonic crystal rod with a 1550
      nm fiber femtosecond laser. A longpass filter was typically used to isolate the
      soliton from the residual in order to avoid excessive energy deposit on the
      sample, which ultimately leads to optical damage. However, since the soliton was
      not cleanly separated from the residual, the criterion for choosing the optimal
      filtering wavelength is lacking. Here, we propose maximizing the ratio between
      the multiphoton signal and the n'th power of the excitation pulse energy as a
      criterion for optimal spectral filtering in SSFS when the soliton shows dramatic
      overlapping with the residual. This optimization is based on the most efficient
      signal generation and entirely depends on physical quantities that can be easily
      measured experimentally. Its application to MPM may reduce tissue damage, while
      maintaining high signal levels for efficient deep penetration.

PMID- 25950645
TI  - Quantitative evaluation of in vivo vital-dye fluorescence endoscopic imaging for
      the detection of Barrett's-associated neoplasia.
AB  - Current imaging tools are associated with inconsistent sensitivity and
      specificity for detection of Barrett's-associated neoplasia. Optical imaging has
      shown promise in improving the classification of neoplasia in vivo. The goal of
      this pilot study was to evaluate whether in vivo vital dye fluorescence imaging
      (VFI) has the potential to improve the accuracy of early-detection of Barrett's
      associated neoplasia. In vivo endoscopic VFI images were collected from 65 sites
      in 14 patients with confirmed Barrett's esophagus (BE), dysplasia, oresophageal
      adenocarcinoma using a modular video endoscope and a high-resolution
      microendoscope(HRME). Qualitative image features were compared to histology; VFI
      and HRME images show changes in glandular structure associated with neoplastic
      progression. Quantitative image features in VFI images were identified for
      objective image classification of metaplasia and neoplasia, and a diagnostic
      algorithm was developed using leave-one-out cross validation. Three image
      features extracted from VFI images were used to classify tissue as neoplastic or
      not with a sensitivity of 87.8% and a specificity of 77.6% (AUC = 0.878). A
      multimodal approach incorporating VFI and HRME imaging can delineate epithelial
      changes present in Barrett's-associated neoplasia. Quantitative analysis of VFI
      images may provide a means for objective interpretation of BE during
      surveillance.

PMID- 25950646
TI  - Spontaneous Magnetization in Homometallic MU6-Oxalate Coordination Polymers.
AB  - The reaction of 1,2,4-triazole and NaF with M(ox) (M = transition-metal dication;
      ox = oxalate dianion) under hydrothermal conditions has led to the isolation of a
      variety of hybrid organic-inorganic coordination polymers. Four structurally
      different 3D networks were obtained, depending on the transition metal, with
      stoichiometry [M2(H2O)(MU2-ox)][M2(MU3-trz)6] [M = Fe (1), Co (2), Ni (3)],
      [Zn2(H2O)(MU3-trz)2(MU2-ox)] (4), [Mn3(MU3-trz)2(MU6-ox)(MU3-F)2] (5), and
      [Fe3(MU3-trz)2(MU6-ox)(MU2-F)2] (6). In all cases, the magnetic behavior is
      dominated by antiferromagnetic exchange interactions between paramagnetic
      centers. Remarkably, 5 and 6 present a novel magnetic connectivity around the
      oxalate anion: a MU6-bridging mode. This magnetic geometry promotes multiple
      triangular arrangements among antiferromagnetically coupled spin carriers,
      resulting in a complex magnetic network because of the presence of competing
      interactions. These materials exhibit spontaneous magnetization below 9 and 66 K,
      respectively. 

PMID- 25950647
TI  - Risk of Substantial Intraocular Bleeding With Novel Oral Anticoagulants:
      Systematic Review and Meta-analysis.
AB  - IMPORTANCE: In noninferiority trials, novel oral anticoagulants (NOACs), also
      known as non-vitamin K oral anticoagulants, were at least noninferior to standard
      care in the prevention of most prothrombotic conditions. However, differences
      exist in the safety profile of antithrombotic drugs, and little is known about
      their intraocular bleeding risk. OBJECTIVE: To evaluate the risk of substantial
      intraocular bleeding associated with NOACs. DATA SOURCES: MEDLINE, Cochrane
      Library, SciELO collection, and Web of Science databases were searched from
      inception to November 2014, as well as other systematic reviews and regulatory
      agencies documentation. STUDY SELECTION: All phase 3 randomized clinical trials
      (RCTs) comparing NOACs with any other control that reported intraocular bleeding
      events. DATA EXTRACTION AND SYNTHESIS: Data were extracted independently by 2 of
      the authors and pooled using random-effects meta-analysis. Heterogeneity was
      assessed with the I2 test. MAIN OUTCOMES AND MEASURES: Substantial intraocular
      bleeding was evaluated with pooled risk ratios (RRs) and 95% CIs. RESULTS:
      Seventeen RCTs were included. In patients with atrial fibrillation, no difference
      was identified between NOACs and vitamin K antagonists (RR, 0.84; 95% CI, 0.59
      1.19; I2 = 35%; 5 RCTs), and no increased risk was identified compared with
      acetylsalicylic acid (RR, 14.96; 95% CI, 0.85-262.00; 1 RCT). In patients with
      venous thromboembolism, no increased risk of substantial intraocular bleeding
      compared with sequential treatment with low-molecular-weight heparin and a
      vitamin K antagonist (RR, 0.67; 95% CI, 0.37-1.20; I2 = 0%; 5 RCTs) was
      identified. Regarding patients who underwent orthopedic surgery, the risk was not
      different between NOACs and low-molecular-weight heparin (RR, 2.13; 95% CI, 0.22
      20.50; I2 = 0%; 5 RCTs). CONCLUSIONS AND RELEVANCE: Randomized data suggest that
      no differences exist in the risk of substantial intraocular bleeding between
      NOACs and other antithrombotic drugs. However, the number of events was scarce so
      that additional studies from larger databases that monitor patients under
      conditions of ophthalmologic routine clinical practice should be performed to
      better characterize the safety profile of NOACs.

PMID- 25950648
TI  - Lung-Dominant Connective Tissue Disease: Clinical, Radiologic, and Histologic
      Features.
AB  - BACKGROUND: Lung-dominant connective tissue disease (LD-CTD) is a disease concept
      for interstitial pneumonia; however, it has not been robustly validated. This
      study was conducted to elucidate the clinical, radiologic, and histologic
      features of LD-CTD. METHODS: We retrospectively reviewed 44 consecutive patients
      with serologically defined LD-CTD who underwent surgical lung biopsy. Patients
      were identified as having LD-CTD if they had specific autoantibodies but did not
      meet the criteria for connective tissue disease. We conducted a multidisciplinary
      diagnosis and evaluated major histologic patterns according to the current
      idiopathic interstitial pneumonias (IIPs) classification of 2013. Characteristic
      histologic features for LD-CTD (eg, prominent plasmacytic infiltration, lymphoid
      aggregates with germinal centers), high-resolution CT (HRCT) scan patterns, and
      prognosis were also assessed. RESULTS: The major histologic patterns were usual
      interstitial pneumonia (UIP) in 25 patients and nonspecific interstitial
      pneumonia (NSIP) in 13 patients. Two or more characteristic histologic features
      for LD-CTD were observed in 15 patients with histologic UIP (h-UIP) and 11
      patients with histologic NSIP (h-NSIP). Fifteen patients with h-UIP (60%) showed
      an inconsistent UIP pattern on HRCT scan. After multidisciplinary discussion
      (MDD), 18 patients with h-UIP were labeled as having unclassifiable IIP. The
      annual change in percent predicted FVC improved significantly in patients with h
      NSIP (P = .002), who also had better survival than those with h-UIP (P = .031).
      In contrast, survival was not associated with HRCT scan pattern (P = .79).
      CONCLUSIONS: The major histologic patterns in LD-CTD were UIP followed by NSIP.
      Two-thirds of patients had characteristic histologic features for LD-CTD. A
      majority of patients with h-UIP were considered to have unclassifiable IIP based
      on MDD. Patients with h-UIP had worse survival than those with h-NSIP.

PMID- 25950649
TI  - Three-Dimensional Au Microlattices as Positive Electrodes for Li-O2 Batteries.
AB  - We demonstrate the feasibility of using a 3-dimensional gold microlattice with a
      periodic porous structure and independently tunable surface composition as a Li
      O2 battery cathode. The structure provides a platform for studying
      electrochemical reactions in architected Li-O2 electrodes with large (300 MUm)
      pore sizes. The lack of carbon and chemical binders in these Au microlattices
      enabled the investigation of chemical and morphological processes that occur on
      the surfaces of the microlattice during cycling. Li-O2 cells with Au microlattice
      cathodes were discharged in 0.5 M lithium-bis(trifluoromethane)sulfonamide
      (LiTFSI) in a 1,2-dimethoxyethane (DME) electrolyte, with lithium metal foil as
      the anode. SEM analysis of microlattice cathodes after first discharge revealed
      the presence of toroidal-shaped 500-700 nm particles covering the surface of the
      electrode, which disappeared upon subsequent charging. Raman and FTIR
      spectroscopy analysis determined these particulates to be Li2O2. The morphology
      of discharge products evolved with cycling into micrometer-sized clusters of
      arranged "platelets", with a higher amount of side reaction products such as
      Li2CO3 and LiOH. This work shows that properly designed 3-dimensional architected
      materials may provide a useful foundation for investigating fundamental surface
      electrochemistry while simultaneously enabling mechanical robustness and
      enhancing the surface area over a factor of 30 compared with a thin film with the
      same foot print. 

PMID- 25950650
TI  - Anatomy of Shoulder Girdle Muscle Modifications and Walking Adaptation in the
      Scaly Chinese Pangolin (Manis Pentadactyla Pentadactyla: Pholidota) Compared with
      the Partially Osteoderm-Clad Armadillos (Dasypodidae).
AB  - Because pangolins are unique mammals with a body and limbs almost entirely
      sheathed in hard keratinous overlapping scales and with digging and climbing
      abilities, the shoulder girdle muscles may differ significantly from those of
      other mammals including the partially osteoderm-clad armadillos. Therefore, we
      conducted a functional anatomical study of the shoulder girdle muscles in Chinese
      pangolins (Manis pentadactyla pentadactyla, Pholidota) and some armadillo species
      (Dasypodidae). Our CT scans revealed that the pangolin's overlapping scales are
      hard structures completely encasing the limbs. The armadillo's limbs, however,
      are covered with small relatively soft non-overlapping scales embedded in the
      skin, and articulate completely free of the hard osteodermal carapace. The
      attachments of some shoulder girdle muscles in the pangolin have moved from the
      surrounding edges of the scapula to the spine, and they, therefore, fully cover
      the scapula. In addition, some pangolin shoulder girdle muscles cross the
      shoulder joint to insert on the distal humerus, but this does not occur in
      armadillos. We cannot rule out the possibility that these muscle modifications
      represent adaptations for digging and/or climbing in pangolins. Our results and
      previous literature do not establish specific links between them and locomotive
      modes. However, we propose that the Chinese pangolin may use its derived muscular
      features when walking to move its armor-restricted forelimbs more effectively by
      swinging its head from side to side.

PMID- 25950652
TI  - Variations in label information and nicotine levels in electronic cigarette
      refill liquids in South Korea: regulation challenges.
AB  - BACKGROUND: In South Korea, the consumption of liquid nicotine used in electronic
      cigarettes has dramatically increased from 4310 L in 2012 to 7220 L in 2013. This
      study aimed to examine the level of heterogeneity of contents of the labels and
      discrepancy of the nicotine content between that indicated on the label and the
      actual values for electronic cigarette liquid refill products in South Korea.
      METHODS: We purchased 32 electronic cigarette liquid refill products (17 Korean
      domestic, 15 imported ones) and one pure nicotine product at six different
      electronic cigarette retail stores in Seoul between May and June 2014. The actual
      nicotine concentrations of each product were measured by a blinded analyst at
      Roswell Park Cancer Institute, Buffalo, NY, USA. RESULTS: Three out of 15
      imported liquid refill products provided manufacturing dates, while expiration
      dates were available on eight products. The range of nicotine concentration was
      from "not detected" to 17.5 mg/mL. Labeling discrepancies of the concentrations
      ranged from -32.2% to 3.3% among electronic cigarette liquid refill products. The
      highest concentration (150.3 +/- 7.9 mg/mL) was found in a sample labeled as
      "pure nicotine". CONCLUSIONS: There is no standardization of labelling among
      electronic cigarette liquids sampled from retail stores and the labels did not
      accurately reflect the content. One product labeled "pure nicotine" raises
      concerns, since it may be poisonous to consumers, especially to children. This
      study revealed the urgent need for the development of product regulations in
      South Korea.

PMID- 25950653
TI  - Technical efficiency and organ transplant performance: a mixed-method approach.
AB  - Mixed methods research is interesting to understand complex processes. Organ
      transplants are complex processes in need of improved final performance in times
      of budgetary restrictions. As the main objective a mixed method approach is used
      in this article to quantify the technical efficiency and the excellence achieved
      in organ transplant systems and to prove the influence of organizational
      structures and internal processes in the observed technical efficiency. The
      results show that it is possible to implement mechanisms for the measurement of
      the different components by making use of quantitative and qualitative
      methodologies. The analysis show a positive relationship between the levels
      related to the Baldrige indicators and the observed technical efficiency in the
      donation and transplant units of the 11 analyzed hospitals. Therefore it is
      possible to conclude that high levels in the Baldrige indexes are a necessary
      condition to reach an increased level of the service offered. 

PMID- 25950651
TI  - A Scoping Review of Observational Studies Examining Relationships between
      Environmental Behaviors and Health Behaviors.
AB  - Individual lifestyles are key drivers of both environmental change and chronic
      disease. We undertook a scoping review of peer-reviewed studies which examined
      associations between environmental and health behaviors of individuals in high
      income countries. We searched EconLit, Medline, BIOSIS and the Social Science
      Citation Index. A total of 136 studies were included. The majority were USA-based
      cross-sectional studies using self-reported measures. Most of the evidence
      related to travel behavior, particularly active travel (walking and cycling) and
      physical activity (92 studies) or sedentary behaviors (19 studies). Associations
      of public transport use with physical activity were examined in 18 studies, and
      with sedentary behavior in one study. Four studies examined associations between
      car use and physical activity. A small number included other environmental
      behaviors (food-related behaviors (n = 14), including organic food, locally
      sourced food and plate waste) and other health behaviors ((n = 20) smoking,
      dietary intake, alcohol). These results suggest that research on individual
      environmental and health behaviors consists largely of studies examining
      associations between travel mode and levels of physical activity. There appears
      to be less research on associations between other behaviors with environmental
      and health impacts, and very few longitudinal studies in any domain. 

PMID- 25950654
TI  - Development of robust antibody purification by optimizing protein-A
      chromatography in combination with precipitation methodologies.
AB  - To be administered to patients, therapeutic monoclonal antibodies must have very
      high purity, with process related impurities like host-cell proteins (HCPs) and
      DNA reduced to <100 ppm and <10 ppb, respectively, relative to desired product.
      Traditionally, Protein-A chromatography as a capture step has been the work horse
      for clearing a large proportion of these impurities. However, remaining levels of
      process and product related impurities still present significant challenges on
      the development of polishing steps further downstream. In this study, we have
      incorporated high throughput screening to evaluate three areas of separation: (i)
      Harvest treatment; (ii) Protein-A Chromatography; and (iii) Low pH Viral
      Inactivation. Precipitation with low pH treatment of cell culture harvest
      resulted in selective removal of impurities while manipulating the pH of wash
      buffers used in Protein-A chromatography and incorporating wash additives that
      disrupt various modes of protein-protein interaction resulted in further and more
      pronounced reduction in impurity levels. In addition, our study also demonstrate
      that optimizing the neutralization pH post Protein-A elution can result in
      selective removal of impurities. When applied over multiple mAbs, this
      optimization method proved to be very robust and the strategy provides a new and
      improved purification process that reduces process related impurities like HCPs
      and DNA to drug substance specifications with just one chromatography column and
      open avenues for significant decrease in operating costs in monoclonal antibody
      purification.

PMID- 25950655
TI  - A Molecular Nanotube with Three-Dimensional pi-Conjugation.
AB  - A pi-conjugated twelve-porphyrin tube is synthesized in 32% yield by a template
      directed coupling reaction that joins together six porphyrin dimers, forming
      twelve new C-C bonds. The nanotube has two bound templates, enclosing an internal
      volume of approximately 4.5 nm(3). Its UV/Vis/NIR absorption and fluorescence
      spectra resemble those of a previously reported six-porphyrin ring, but are red
      shifted by approximately 300 cm(-1), reflecting increased conjugation. Ultrafast
      fluorescence spectroscopy demonstrates extensive excited-state delocalization.
      Transfer of electronic excitation from an initially formed state polarized in the
      direction of the nanotube axis (z axis) to an excited state polarized in the xy
      plane occurs within 200 fs, resulting in a negative fluorescence anisotropy on
      excitation at 742 nm.

PMID- 25950656
TI  - A Halogen-Bonded Dimeric Resorcinarene Capsule.
AB  - Iodine (I2) acts as a bifunctional halogen-bond donor connecting two macrocyclic
      molecules of the bowl-shaped halogen-bond acceptor, N-cyclohexyl ammonium
      resorcinarene chloride 1, to form the dimeric capsule [(1,4-dioxane)3@1(2)(I2)2].
      The dimeric capsule is constructed solely through halogen bonds and has a single
      cavity (V=511 A(3)) large enough to encapsulate three 1,4-dioxane guest
      molecules.

PMID- 25950657
TI  - Reliability of Force Application to Instrumented Climbing Holds in Elite
      Climbers.
AB  - Multiaxial force sensors were applied to measure interaction forces during
      dynamic movements, such as climbing. When interaction forces are interpreted,
      minimal detectable changes, typical errors, and coefficients of variation of
      related performance metrics should be quantified. Thus, the presented study
      evaluated absolute and relative between-trial reliability with and without
      previous familiarization trials. Eleven Swiss elite climbers (5 females, 6 males)
      were tested during 2 repetitive climbing sequences (including 4 instrumented
      holds: 2 crimps, 1 undercling, 1 sloper). To ensure comparable relative
      intensity, females climbed at 20 degrees , 25 degrees , 30 degrees , 25 degrees ,
      and 20 degrees  wall inclination, while males climbed at 25 degrees , 30 degrees
      , 35 degrees , 30 degrees , and 25 degrees . Contact time, maximal resultant
      force, mean resultant force, impulse, and the number of load changes were
      analyzed at the lowest inclination. Acceptable to good between-trial reliability
      was found for nearly all holds and performance metrics. Performance analyses
      after 5 minutes of familiarization on the unknown boulder, which equals up to 3
      trials, yielded to higher variability compared with performance analyses after
      several familiarization trials. Accordingly, the majority of absolute and
      relative reliability data improved after familiarization trails. Thus, to be
      detectable, interventional changes have to exceed higher biological variability
      during on-sight conditions than during red-point conditions. 

PMID- 25950658
TI  - Solubility and crystal nucleation in organic solvents of two polymorphs of
      curcumin.
AB  - Two crystal polymorphs of 1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5
      dione (curcumin) have been obtained by crystallization from ethanol (EtOH)
      solution. The polymorphs have been characterized by differential scanning
      calorimetry, infrared spectroscopy, and X-ray powder diffraction and shown to be
      the previously described forms I and III. The solubility of both polymorphs in
      EtOH and of one polymorph in ethyl acetate (EA) has been measured between 10
      degrees C and 50 degrees C with a gravimetric method. Primary nucleation of
      curcumin from EtOH solution has been investigated in 520 constant temperature
      crystallization experiments in sealed, magnetically stirred vials under different
      conditions of supersaturation, temperature, and agitation rate. By a
      thermodynamic analysis of the melting data and solubility of form I, the solid
      state activity is estimated from 10 degrees C up to the melting point. The
      solubility is lower in EtOH than in EA, and in both solvents, a positive
      deviation from Raoult's law is observed. Form I has lower solubility than form
      III and is accordingly thermodynamically more stable over the investigated
      temperature interval. Extrapolation of solubility regression models indicates
      that there should be a low-temperature enantiotropic transition point, below
      which form I will be metastable. By slurry conversion experiments, it is
      established that this temperature is below -30 degrees C. All nucleation
      experiments resulted in the stable form I. The induction time is observed to
      decrease with increasing agitation rate up to a certain point, and then increase
      with further increasing agitation rate; a trend previously observed for other
      compounds. By correlating the induction time data obtained at different
      supersaturation and temperature, the interfacial energy of form I in EtOH is
      estimated to be 3.0 mJ/m(2) .

PMID- 25950659
TI  - Conditional cell ablation via diphtheria toxin reveals distinct requirements for
      the basal plate in the regional identity of diencephalic subpopulations.
AB  - The mammalian diencephalon is the caudal derivative of the embryonic forebrain.
      Early events in diencephalic regionalization include its subdivision along the
      dorsoventral and anteroposterior axes. The prosomeric model by Puelles and
      Rubenstein (1993) suggests that the alar plate of the posterior diencephalon is
      partitioned into three different prosomeres (designated p1-p3), which develop
      into the pretectum, thalamus, and prethalamus, respectively. Here, we report the
      developmental consequences of genetic ablation of cell populations from the
      diencephalic basal plate. The strategy for conditionally regulated cell ablation
      is based on the targeted expression of the diphtheria toxin gene (DTA) to the
      diencephalic basal plate via tamoxifen- induced, Cre-mediated recombination of
      the ROSA(DTA) allele. We show that activation of DTA leads to specific cell loss
      in the basal plate of the posterior diencephalon, and disrupted early
      regionalization of distinct alar territories. In the basal plate-deficient
      embryos, the p1 alar plate exhibited reduced expression of subtype-specific
      markers in the pretectum, whereas p2 alar plate failed to further subdivide into
      two discrete thalamic subpopulations. We also show that these defects lead to
      abnormal nuclear organization at later developmental stages. Our data have
      implications for increased understanding of the interactive roles between
      discrete diencephalic compartments.

PMID- 25950660
TI  - The Prevalence of Pseudoexfoliation and the Long-term Changes in Eyes With
      Pseudoexfoliation in a South Indian Population.
AB  - PURPOSE: To report the prevalence, long-term changes and associated factors for
      pseudoexfoliation (PEX) in a population aged 40 years and above from rural and
      urban south India. MATERIALS AND METHODS: At baseline (the Chennai Glaucoma
      Study), 7774 subjects were examined. After 6 years, as a part of the incidence
      study, 133 of the 290 subjects diagnosed with PEX at baseline were reexamined for
      long-term changes. Participants had detailed examination at base hospital.
      RESULTS: At baseline PEX was noted in 290 [3.73%, 95% confidence interval (CI),
      3.3-4.2] subjects. It was associated with glaucoma in 24 (8.3%), ocular
      hypertension (OHT) in 21 (7.2%), and occludable angles in 24 (8.3%) subjects. The
      age-adjusted and sex-adjusted prevalence was 3.41% (95% CI, 3.39-3.43).
      Increasing age was a significant associated factor. Using the 40- to 49-year age
      group as a reference, the odds ratio increased from 8.4 (95% CI, 4.1-17.1) for
      the 50- to 59-year age group to 51.2 (95% CI, 25.8-101.6) for the 70 years and
      above age group. Other associated factors were rural residence (P<0.001), higher
      intraocular pressure (P<0.001), cataract (P<0.001), being underweight (P=0.01),
      manual labor (P=0.03), and aphakia (P<0.001). Of the 133 subjects reexamined, 8
      (6.0%) subjects developed glaucoma and all had OHT at baseline. Rates of cataract
      surgery were (P<0.001) higher in subjects with PEX. CONCLUSION: Prevalence of PEX
      was higher in rural population and baseline OHT was a significant factor for
      conversion to glaucoma.

PMID- 25950661
TI  - Correlation of Intraocular Pressure Between Both Eyes After Bilateral Selective
      Laser Trabeculoplasty in Open-angle Glaucoma.
AB  - PURPOSE: To investigate the correlation of intraocular pressure (IOP)-lowering
      effects of selective laser trabeculoplasty (SLT) between the 2 eyes treated with
      SLT in open-angle glaucoma (OAG). METHODS: This prospective cohort study
      sequentially recruited subjects with bilateral OAG. All subjects received a
      single session of 360-degree SLT treatment. Success was defined as IOP reduction
      of >=20%. Spearman correlation was used to compare the following parameters
      between the 2 eyes following SLT: IOP at day 1, 1 week, and 1 month; percentage
      of success; and IOP reduction. RESULTS: In 84 eyes of 42 subjects that received
      bilateral SLT treatment, both eyes had statistically comparable baseline
      characteristics. There were significant correlations between the IOP in both eyes
      at all time intervals following SLT as well as for the percentage of IOP
      reduction and the success rate at 1 month after SLT (all r>=0.7, P<0.0001). A
      total of 42.9% of subjects had bilateral success and 38.1% had bilateral
      nonsuccess with a significant correlation between both eyes in these 2 groups
      (Spearman r>0.6, P<0.02). Nineteen percent had success in 1 eye and nonsuccess in
      the fellow eye with an inverse correlation between the 2 eyes (Spearman r=-0.7,
      P=0.03). CONCLUSION: There is a strong and significant correlation in the IOP
      lowering response to SLT between both eyes in near 80% of treated OAG subjects,
      whereas near 20% had an asymmetrical and inverse response to SLT between both the
      eyes.

PMID- 25950662
TI  - Bilateral Subretinal Fluid Mimicking Subretinal Neovascularization Within 24
      Hours After Selective Laser Trabeculoplasty.
AB  - PURPOSE: Selective laser trabeculoplasty (SLT), which is widely regarded as a
      safe procedure, is a frequently used treatment for open-angle glaucoma. Although
      it is presumed to be associated with an inflammatory cascade and possible
      postoperative inflammation, only 2 cases of SLT complicated by cystoid macular
      edema have been previously reported. Until now there are no previous reports of
      SLT causing subretinal fluid (SRF). METHODS/IMPORTANCE: Clinical examination,
      optical coherence tomography, and fluorescein angiography demonstrated a
      previously unreported clinical entity consisting of bilateral SRF, developing
      within 24 hours of bilateral inferior 180-degree SLT for open-angle glaucoma.
      RESULTS: Rapid bilateral, subjective loss of vision occurred within 24 hours post
      SLT. This was associated with bilateral SRF resulting in 48 MUm (OD) and 35 MUm
      (OS) increase in macular thickness on optical coherence tomography. Fundus
      fluorescein angiography demonstrated profuse, well-demarcated subfoveal leakage.
      SRF resolved within 4 days, but eventual best corrected visual acuity was
      subjectively and objectively decreased. CONCLUSIONS: The sudden onset of loss of
      vision and the development of subfoveal SRF within 24 hours of SLT strongly
      suggests cause and effect. This previously unreported clinical entity of
      bilateral SRF within 24 hours of SLT may be secondary to an intraocular
      inflammatory cascade, similar to previous hypotheses regarding 3 cases of cystoid
      macular edema post-SLT. Given the dramatic initial loss of vision and compromised
      long-term visual outcome, clinicians and patients need to be informed of this new
      clinical entity of SLT associated with SRF and permanent retinal pigment
      epithelial changes.

PMID- 25950663
TI  - Probing reversible chemistry in coenzyme B12 -dependent ethanolamine ammonia
      lyase with kinetic isotope effects.
AB  - Coenzyme B12 -dependent enzymes such as ethanolamine ammonia lyase have
      remarkable catalytic power and some unique properties that enable detailed
      analysis of the reaction chemistry and associated dynamics. By selectively
      deuterating the substrate (ethanolamine) and/or the beta-carbon of the 5'
      deoxyadenosyl moiety of the intrinsic coenzyme B12 , it was possible to
      experimentally probe both the forward and reverse hydrogen atom transfers between
      the 5'-deoxyadenosyl radical and substrate during single-turnover stopped-flow
      measurements. These data are interpreted within the context of a kinetic model
      where the 5'-deoxyadenosyl radical intermediate may be quasi-stable and
      rearrangement of the substrate radical is essentially irreversible. Global
      fitting of these data allows estimation of the intrinsic rate constants
      associated with Co?C homolysis and initial H-abstraction steps. In contrast to
      previous stopped-flow studies, the apparent kinetic isotope effects are found to
      be relatively small. 

PMID- 25950664
TI  - Vegetation shift from deciduous to evergreen dwarf shrubs in response to
      selective herbivory offsets carbon losses: evidence from 19 years of warming and
      simulated herbivory in the subarctic tundra.
AB  - Selective herbivory of palatable plant species provides a competitive advantage
      for unpalatable plant species, which often have slow growth rates and produce
      slowly decomposable litter. We hypothesized that through a shift in the
      vegetation community from palatable, deciduous dwarf shrubs to unpalatable,
      evergreen dwarf shrubs, selective herbivory may counteract the increased shrub
      abundance that is otherwise found in tundra ecosystems, in turn interacting with
      the responses of ecosystem carbon (C) stocks and CO2 balance to climatic warming.
      We tested this hypothesis in a 19-year field experiment with factorial treatments
      of warming and simulated herbivory on the dominant deciduous dwarf shrub
      Vaccinium myrtillus. Warming was associated with a significantly increased
      vegetation abundance, with the strongest effect on deciduous dwarf shrubs,
      resulting in greater rates of both gross ecosystem production (GEP) and ecosystem
      respiration (ER) as well as increased C stocks. Simulated herbivory increased the
      abundance of evergreen dwarf shrubs, most importantly Empetrum nigrum ssp.
      hermaphroditum, which led to a recent shift in the dominant vegetation from
      deciduous to evergreen dwarf shrubs. Simulated herbivory caused no effect on GEP
      and ER or the total ecosystem C stocks, indicating that the vegetation shift
      counteracted the herbivore-induced C loss from the system. A larger proportion of
      the total ecosystem C stock was found aboveground, rather than belowground, in
      plots treated with simulated herbivory. We conclude that by providing a
      competitive advantage to unpalatable plant species with slow growth rates and
      long life spans, selective herbivory may promote aboveground C stocks in a
      warming tundra ecosystem and, through this mechanism, counteract C losses that
      result from plant biomass consumption. 

PMID- 25950665
TI  - Cervicovaginal cytology in the posttreatment surveillance of women with cervical
      cancer.
AB  - OBJECTIVE: Our aim in this study was to determine the value of cervicovaginal
      cytology in surveillance for recurrent cervical cancer. MATERIALS AND METHODS:
      Charts were reviewed for 136 women with cervical cancer presenting at least 3
      months after treatment with curative intent for a previously scheduled
      surveillance visit to Cook County Hospital between September 1, 1994, and
      December 31, 1995. Results of cytology and symptoms elicited by history and
      physical examination were compared to recurrences occurring within 6 months.
      RESULTS: Recurrences were identified in eight patients. Sites of recurrence
      included cervix-vaginal cuff (n = 5), pelvic wall (n = 1), and paraaortic or
      supraclavicular lymph nodes (n = 2). Sixteen women had symptoms, and seven had
      abnormal physical findings. One woman had malignant cytology. Sensitivity,
      specificity, and positive and negative predictive value were 38, 90, 23, and 96%,
      respectively, for symptoms; 50, 99, 80, and 97%, respectively, for examination;
      and 13, 100, 100, and 95%, respectively, for cytology. CONCLUSION: After cervical
      cancer treatment, cervicovaginal cytology was a more specific but less sensitive
      predictor of recurrence within 6 months than were symptoms or physical findings.

PMID- 25950666
TI  - Relationship between red cell folate and cervical intraepithelial neoplasia and
      cervical human papillomavirus infection.
AB  - OBJECTIVE: The aim of this study was to determine the relationship between red
      cell folate levels and the presence of cervical intraepithelial neoplasia (CIN)
      or cervical human papillomavirus infection (HPV) (or both). For that purpose, we
      designed a case-control study. MATERIALS AND METHODS: One hundred three
      asymptomatic women who were between the ages of 20 and 76 and attending the
      gynecological clinic of the Military Hospital in Bogota, Colombia, were selected.
      Their mean age was 37.9 years. Inclusion criteria combined a colposcopic
      examination and a cervicovaginal Papanicolaou smear; accordingly, patients were
      divided into women without CIN or HPV (55 women, the control group) and women
      with CIN or HPV (or both) (48 women, the study group). Red cell folate levels
      were determined by radioimmunoassay. RESULTS: Statistically significant
      differences in folate levels were found between cases [2.55 ng/ml; standard
      deviation, 0.75; 95% confidence interval, 2.34-2.73] and controls (2.96 ng/ml;
      standard deviation, 0.77; 95% confidence interval, 2.75-3.14; p < .008). The odds
      ratio between the folate levels and CIN or HPV (or both) was 0.49 (p = .01). Red
      cell folate levels of the individuals participating in this study were not found
      to be associated with parity, the use of oral contraceptives, cigarette smoking,
      or age. CONCLUSIONS: High red cell folate levels appear to provide a protective
      effect against the development of CIN or HPV (or both).

PMID- 25950667
TI  - Management of the abnormal papanicolaou smear during pregnancy: lessons for
      quality improvement.
AB  - OBJECTIVE: Our goal in this study was to evaluate the management of pregnant
      patients with abnormal Papanicolaou smears. MATERIALS AND METHODS: We reviewed
      the records of 292 patients undergoing colposcopy to evaluate abnormal cervical
      cytology during pregnancy. RESULTS: A total of 32 (11%) of the subjects had
      Papanicolaou smears demonstrating atypical glandular cells of undetermined
      significance; 178 (61%) had low-grade squamous intraepithelial lesions; 69
      (23.6%) had high-grade squamous intraepithelial lesions; and 2 (1%) had a
      malignancy. The first colposcopy was performed most commonly during gestational
      week 24. Colposcopy showed findings consistent with minor changes in 154 cases
      (53%) and with major changes in 61 (21%). Only 27 patients (9% of the total)
      underwent a colposcopically directed biopsy, and 51 (83.6%) of the 61 patients
      with a colposcopic impression of cervical intraepithelial neoplasia grade 2 or
      greater did not undergo biopsy. Only 24 (26%) of the 91 patients scheduled for
      follow-up colposcopy during pregnancy complied, and 123 of the 292 patients (42%)
      returned for follow-up examinations after delivery. Four patients had an invasive
      cervical carcinoma diagnosed in the 12 months immediately after delivery.
      Although the first intrapregnancy colposcopy in two of these patients noted
      findings consistent with cervical intraepithelial neoplasia grade 2 or greater,
      none of the four underwent biopsy during pregnancy. CONCLUSIONS: Evaluation of
      cytological abnormalities is frequently suboptimal during pregnancy. The
      threshold for colposcopically directed biopsy is often modified during pregnancy
      in a way that may be harmful to the patient. Extra effort is needed to tailor
      follow-up to the patient's need and to improve patient compliance.

PMID- 25950668
TI  - Comparison of the hybrid capture test and polymerase chain reaction in
      identifying women who have an atypical squamous cell of undetermined significance
      papanicolaou smear and need colposcopy.
AB  - OBJECTIVES: The objective of this study was to detect human papillomavirus (HPV)
      in women with a newly diagnosed atypical squamous cells of undetermined
      significance (ASCUS) using the hybrid capture (HC) test and the polymerase chain
      reaction (PCR). We sought to evaluate the accuracy of both tests in identifying
      women with a concomitant cervical intraepithelial neoplasia (CIN). MATERIALS AND
      METHODS: We studied 360 women who had a diagnosis of ASCUS and were referred to
      the colposcopy clinic. Subjects were between 18 and 50 years, had newly diagnosed
      ASCUS, had no history of cervical biopsies or treatment, and were not pregnant. A
      cell sample for HPV testing and colposcopically directed biopsies of lesions were
      obtained. HPV was detected using the Digene HC and PCR systems (Digene, Silver
      Spring, MD). RESULTS: Biopsies showed concomitant CIN in 80 patients (22.2%). Of
      these, 19 had CIN2 or CIN3. HPV-DNA was detected in 76 of the 360 women (21.1%)
      using HC and in 166 of 348 women (47.7%) using PCR. The concordance between HC
      and PCR for detecting HPV was 65%. The sensitivity, specificity, and positive and
      negative predictive values of HC for detecting CIN were 48%, 86%, 50%, and 85%,
      respectively. The sensitivity, specificity, and positive and negative predictive
      values of PCR for detecting CIN were 67%, 58%, 31%, and 86%, respectively.
      Focusing on CIN2 and CIN3 alone, these values were 79%, 82%, 20%, and 99% for HC,
      respectively, and 89%, 55%, 10%, and 99% for PCR, respectively. CONCLUSION: The
      specificity of HC was higher than the specificity of PCR. For this reason, the HC
      might be more useful than PCR as a secondary triage method for detecting CIN in
      women who have incident ASCUS and need colposcopy.

PMID- 25950669
TI  - Predictors of concomitant cervical intraepithelial neoplasia in women with newly
      diagnosed atypical squamous cells of undetermined significance.
AB  - OBJECTIVE: The percentage of women with atypical squamous cells of undetermined
      significance (ASCUS) with concomitant cervical intraepithelial neoplasia (CIN) is
      relatively high, varying between 18% and 30%, depending on the series. The
      objective of this study was to identify factors other than cervical human
      papillomavirus (HPV) infection that would help to identify women with newly
      diagnosed ASCUS and in need of referral to colposcopy. MATERIALS AND METHODS: A
      total of 360 eligible women in whom ASCUS was diagnosed and who were referred to
      the colposcopy clinic of Saint-Sacrement Hospital in Quebec City were included in
      this study (participation rate, 92%). Eligible women were those aged between 18
      and 50 years, with newly diagnosed ASCUS, with no history of cervical biopsies or
      treatment, and not pregnant at the time of their visit. During their
      gynecological visit, a cell sample was collected for HPV testing, and
      colposcopically directed biopsies of lesions were obtained. HPVs were detected
      using the Digene hybrid capture test. Logistical regression was used to estimate
      odds ratios (ORs) for concomitant CIN and their 95% confidence intervals (CIs).
      All ORs were adjusted for cervical HPV infection and other risk factors. RESULTS:
      Cervical HPV infection was the factor most strongly related to concomitant CIN
      (OR = 4.0; 95% CI = 2.2-7.3). After taking into account the presence of cervical
      HPV infection, two variables were significantly associated with concomitant CIN.
      Compared to older women, those aged 35 or younger had a higher risk of
      concomitant CIN (OR - 2.3; 95% CI - 1.3-4.2). Current smoking was positively
      associated with concomitant CIN (OR - 2.7; 95% CI - 1.4-5.1), while there was no
      association between past smoking and concomitant CIN. Having had more than four
      sexual partners in the last 5 years was associated with an OR of 2.1; however,
      this association did not reach statistical significance. Cervical HPV infection,
      younger age, and current smoking were independent determinants of both CIN1 and
      CIN2 and 3. CONCLUSION: Age and smoking status are independent predictors of
      concomitant CIN in women with newly diagnosed ASCUS. When HPV testing is not
      available, clinicians could preferentially refer younger women and those who
      smoke to colposcopy, as they represent a population with ASCUS at high risk of
      concomitant CIN.

PMID- 25950670
TI  - Cervical carcinoma demonstrating tumor-associated tissue eosinophilia: a
      clinicopathological study of 17 patients.
AB  - OBJECTIVES: Our objective in this study was to evaluate the clinicopathological
      significance of tissue eosinophilia associated with invasive cervical carcinomas.
      MATERIALS AND METHODS: All cases of cervical carcinoma treated at the Medical
      College of Georgia between October 1982 and October 1989 were reviewed. We
      obtained data regarding all cases, including age at diagnosis, stage of disease,
      therapy, and outcome. Pathological review of all cases was undertaken to identify
      those patients in whom invasive carcinoma was associated with an intense
      infiltrate of eosinophils. RESULTS: A total of 441 patients with invasive
      cervical carcinomas were treated at the Medical College of Georgia between
      October 1982 and October 1989. Of these patients, 403 had squamous carcinomas, 34
      had adenocarcinomas, 4 had adenosquamous carcinomas, and 18 demonstrated
      tumorassociated tissue eosinophilia (TATE). In all cases TATE was associated with
      squamous cell carcinomas. Patients in whom TATE was identified were younger
      (range, 20-67 years; mean, 40.2 years) than were those patients without TATE
      (range, 17.5-93.5; mean, 54.8 years; p = .0004; t = 3.626, with 233 degrees of
      freedom) No significant difference was noted with regard to size of tumor, stage
      at diagnosis, outcome, or length of survival. CONCLUSION: Although it is an
      interesting and unusual finding when identified in relationship to cervical
      carcinoma, TATE is of no prognostic significance.

PMID- 25950671
TI  - Human Immunodeficiency Virus Localization in Human Papillomavirus-Related, High
      Grade Squamous Intraepithelial Lesions of the Cervix in Women with HIV Infection:
      Microdissection and Molecular Analysis on Formalin-Fixed and Paraffin-Embedded
      Specimens.
AB  - OBJECTIVES: To evaluate a possible mechanism of human immunodeficiency virus
      (HIV) and human papillomavirus (HPV) interaction, we have identified the cervical
      tissue compartments that harbor HIV. MATERIALS AND METHODS: We studied 39
      paraffin-embedded, cervical conization specimens with high-grade cervical
      intraepithelial neoplasia (CIN3) occurring in HIV-infected women. From selected
      intraepithelial HPV-positive nonulcerated specimens (confirmed by in situ
      hybridization), we obtained serial 4- to 5-MUm-thick sections that were stained
      with hematoxylin and eosin, anti-S100 protein, and anti-CD4. The presence of
      intramucosal Langerhans' cells or dendritic cells or CD4-positive cells was
      recorded. Three consecutive, nonmicrodissected, full-thickness sections of the
      same specimens were used for polymerase chain reaction (PCR) analysis (group A).
      Three other uncovered, consecutive sections from the same blocks were examined
      with an inverted microscope, and full-thickness specimens of mucosa were
      dissected from the underlying cervical stroma, were gently removed, and were used
      for PCR (group B). The quality of DNA was checked by HLA-DQa amplification; then
      a nested PCR for HIV proviral DNA was performed. RESULTS: Of group A, 5 of 39
      cases (12.8%) were positive, whereas HIV was not detected in the microdissected
      sections of group B, with or without intraepithelial Langerhans' or CD4 cells.
      CONCLUSIONS: HIV does not affect cervical epithelium. The absence of infected
      Langerhans' or dendritic cells (or both) indicates a migration to the proximal
      lymph nodes of the in ....

PMID- 25950672
TI  - Lichen sclerosus in pregnancy: presentation of two cases.
AB  - Numerous skin diseases occurring in the pregnant patient have been reported. Some
      of these diseases are unique to pregnancy and some, including vulvar
      varicosities, vulvar edema, postpartum labial adhesions, and hematomas, are a
      result of physiological changes of pregnancy or the birth process. In addition, a
      variety of viral and bacterial infectious diseases of the vulva may occur during
      pregnancy. Vulvar neoplasms may also be found in pregnancy. In two patients, ages
      27 and 31, lichen sclerosus first was diagnosed during their initial prenatal
      visits. Only one of the patients was symptomatic. The symptomatic patient used
      topical steroids for relief of vulvar itching. Two patients with lichen sclerosus
      of the vulva in pregnancy are reported, with emphasis on the diagnosis and
      treatment of this condition. 

PMID- 25950673
TI  - Home study course: autumn 1999.
AB  - OBJECTIVES: The Home Study Course is intended for the practicing colposcopist or
      practitioner or practitioner who is seeking to develop or enhance his or her
      colposcopic skills. The goal of the course is to present colposcopic cases that
      are unusual or instructive in terms of apperance, presentation, or management, or
      that demonstrate new and important knowldge in the area of colposcopy or
      pathology. Participants may benefit from reading and studing the material or from
      testing thier knowledge by answering the questions. ACCME ACCREDITATION: The
      American Society for Colposcopy and Cervical Pathology (ASCCP) is accredited by
      the Accreditation Council for Continuing medical education for physicians. The
      ASCCP designates this continuing medical education activity for 1 credit hour in
      Category I of the Physician's Recognition Award of the American Medical
      Association. Credit is available for those who choose to apply. The Home Study
      Course is planned and produced in accordance with the ACCME's Essential Areas and
      Elements.

PMID- 25950674
TI  - The american society for colposcopy and cervical pathology.

PMID- 25950675
TI  - What is the diagnostic workup after biopsy of adenocarcinoma in situ during and
      after pregnancy?

PMID- 25950678
TI  - Influence of edaphic, climatic, and agronomic factors on the composition and
      abundance of nitrifying microorganisms in the rhizosphere of commercial olive
      crops.
AB  - The microbial ecology of the nitrogen cycle in agricultural soils is an issue of
      major interest. We hypothesized a major effect by farm management systems
      (mineral versus organic fertilizers) and a minor influence of soil texture and
      plant variety on the composition and abundance of microbial nitrifiers. We
      explored changes in composition (16S rRNA gene) of ammonia-oxidizing archaea
      (AOA), bacteria (AOB), and nitrite-oxidizing bacteria (NOB), and in abundance of
      AOA and AOB (qPCR of amoA genes) in the rhizosphere of 96 olive orchards
      differing in climatic conditions, agricultural practices, soil properties, and
      olive variety. Majority of archaea were 1.1b thaumarchaeota (soil crenarchaeotic
      group, SCG) closely related to the AOA genus Nitrososphaera. Most AOB (97%) were
      identical to Nitrosospira tenuis and most NOB (76%) were closely related to
      Nitrospira sp. Common factors shaping nitrifiers assemblage composition were pH,
      soil texture, and olive variety. AOB abundance was positively correlated with
      altitude, pH, and clay content, whereas AOA abundances showed significant
      relationships with organic nitrogen content and exchangeable K. The abundances of
      AOA differed significantly among soil textures and olive varieties, and those of
      AOB among soil management systems and olive varieties. Overall, we observed minor
      effects by orchard management system, soil cover crop practices, plantation age,
      or soil organic matter content, and major influence of soil texture, pH, and
      olive tree variety. 

PMID- 25950679
TI  - Immediate Loading of Dental Implants in Edentulous Mandibles by Use of Locator(r)
      Attachments or Dolder(r) Bars: Two-Year Results from a Prospective Randomized
      Clinical Study.
AB  - PURPOSE: The study aims to evaluate survival and incidence of complications for
      pairs of implants placed in the front region of edentulous mandibles and
      immediately loaded with either bar or Locator attachments. MATERIALS AND METHODS:
      Forty-six patients with edentulous mandibles (mean age 69.4 years at inclusion in
      the study; 73.9% male) received two implants in the interforaminal area of the
      symphysis. Dolder bar or Locator attachments, allocated randomly, were then
      attached immediately, and both clips and a framework were fastened to the denture
      by the dental technician within 72 hours. RESULTS: During the first 3 months of
      the 2-year period of observation, eight implants in five patients were lost, and
      were removed. Survival was 89.1% and 93.5% for the bar and Locator groups,
      respectively. During the entire period of observation, 38 prosthetic
      complications required aftercare. Five dentures had to be removed or reworked
      after implant failure, but no superstructure was lost or had to be remade for
      prosthetic reasons. Survival of the original dentures was 93.5% and 95.7% for the
      bar and Locator groups, respectively. CONCLUSION: Within the limitations of this
      study, results from immediate loading of two implants in the edentulous mandible
      with either Locator or bar attachments hardly differed. Prosthetic complications
      and aftercare measures in the Locator group were frequent but easy to handle.
      Ease of repair and cleaning, in particular, might be reasons for choosing the
      single-attachment system.

PMID- 25950681
TI  - Is administration of trastuzumab an independent risk factor for developing
      osteonecrosis of the jaw among metastatic breast cancer patients under zoledronic
      acid treatment?
AB  - One of the most important adverse effects of zoledronic acid (ZA) is
      osteonecrosis of the jaw (ONJ). In previous literature, several risk factors have
      been identified in the development of ONJ. In this study, we aimed to determine
      the role of trastuzumab, an antiangiogenic agent, as an independent risk factor
      for the development of this serious side effect.Our study included 97 patients
      (mean age: 54 +/- 10 years) with breast cancer, recorded in the archives of the
      Istanbul Florence Nightingale Breast Study Group, who received ZA therapy due to
      bone metastases between March 2006 and December 2013. We recorded the patients'
      ages, weights, duration of treatment with ZA, number of ZA infusions, dental
      procedures, anticancer treatments (chemotherapy, aromatase inhibitor,
      trastuzumab), the presence of diabetes mellitus or renal dysfunction, and smoking
      habits.Thirteen patients (13.40%) had developed ONJ. Among the patients with ONJ,
      the mean time of exposure to ZA was 41 months (range: 13-82) and the mean number
      of ZA infusions was 38 (range: 15-56). The duration of treatment with ZA and the
      use of trastuzumab were observed to be 2 factors that influenced the development
      of ONJ (P = 0.049 and P = 0.028, respectively).The development of ONJ under ZA
      treatment may be associated solely with the duration of ZA treatment and the
      concurrent administration of trastuzumab. These findings show that patients who
      are administered trastuzumab for metastatic breast cancer while undergoing ZA
      treatment are prone to developing ONJ. Therefore, we recommend intense clinical
      observation to avoid this particular condition in patients receiving ZA and
      trastuzumab. 

PMID- 25950680
TI  - Human Induced Pluripotent Stem Cells Are Targets for Allogeneic and Autologous
      Natural Killer (NK) Cells and Killing Is Partly Mediated by the Activating NK
      Receptor DNAM-1.
AB  - Human induced pluripotent stem cells (hiPSCs) could be used to generate
      autologous cells for therapeutic purposes, which are expected to be tolerated by
      the recipient. However, iPSC-derived grafts are at risk of giving rise to
      teratomas in the host, if residuals of tumorigenic cells are not rejected by the
      recipient. We have analyzed the susceptibility of hiPSC lines to allogeneic and
      autologous natural killer (NK) cells. IL-2-activated, in contrast to resting NK
      cells killed hiPSC lines efficiently (P = 1.69 x 10(-39)). Notably, the specific
      lysis of the individual hiPSC lines by IL-2-activated NK cells was significantly
      different (P = 1.72 x 10(-6)) and ranged between 46 % and 64 % in 51Cr-release
      assays when compared to K562 cells. The hiPSC lines were killed by both
      allogeneic and autologous NK cells although autologous NK cells were less
      efficient (P=8.63 x 10(-6)). Killing was partly dependent on the activating NK
      receptor DNAM-1 (P = 8.22 x 10(-7)). The DNAM-1 ligands CD112 and CD155 as well
      as the NKG2D ligands MICA and MICB were expressed on the hiPSC lines. Low amounts
      of human leukocyte antigen (HLA) class I proteins, which serve as ligands for
      inhibitory and activating NK receptors were also detected. Thus, the
      susceptibility to NK cell killing appears to constitute a common feature of
      hiPSCs. Therefore, NK cells might reduce the risk of teratoma formation even
      after autologous transplantations of pluripotent stem cell-derived grafts that
      contain traces of pluripotent cells.

PMID- 25950682
TI  - Ashkenazi Jewish origin protects against formation of antibodies to infliximab
      and therapy failure.
AB  - Infliximab is an anti-tumor necrosis factor (TNF) used for treatment of
      inflammatory bowel disease (IBD) as well as rheumatoid arthritis, psoriasis, and
      other inflammatory conditions. Antibodies to infliximab (ATI) develop in
      approximately 45% of infliximab-treated IBD patients and are correlated with loss
      of clinical response. Scarce data exist as to factors which predict infliximab
      immunogenicity.To investigate factors that may predict formation of antibodies to
      infliximab (ATI) and infliximab therapy failure an observational study of
      consecutive IBD patients treated with infliximab between 2009 and 2013 was
      performed. Trough levels of ATI were measured. Patients were monitored for
      disease activity using clinical activity indexes and were classified according to
      ATI formation and clinical response. All clinical and demographic parameters were
      analyzed for association with the designated outcomes.One hundred fifty-nine
      patients were included and 1505 sera were tested. On multivariate analysis,
      Jewish Ashkenazi ethnicity was protective against both development of ATI (odds
      ratio [OR] 0.35, 95% confidence interval [CI] 0.17-0.7, P = 0.005) and treatment
      failure (OR 0.29, 95% CI 0.13-0.66, P = 0.003). Concomitant immunomodulator
      therapy was also negatively associated with immunogenicity and infliximab therapy
      failure (OR 0.31, 95% CI 0.15-0.65, P = 0.002; OR 0.42 95% CI 0.18-0.99, p =
      0.04, respectively), whereas episodic therapy was positively associated with both
      outcomes (OR 4.2 95% CI 1.07-16.1, p = 0.04, OR 4.45 95% CI 1.2-16.6, p = 0.026
      respectively). All other variables, including IBD type, gender, weight, age,
      smoking status and disease duration, were not predictive of ATI formation or
      clinical failure. However, among Crohn's disease patients, a non-stricturing non
      penetrating phenotype was protective against ATI formation (OR 0.4, 95% CI 0.14
      0.96, p = 0.04). P = 0.04, respectively), whereas episodic/interrupted therapy
      was positively associated with both outcomes (OR 4.2, 95% CI 1.07-16.1, P = 0.04;
      OR 4.45, 95% CI 1.2-16.6, P = 0.026, respectively). All other variables,
      including IBD type, sex, weight, age, smoking status, and disease duration, were
      not predictive of ATI formation or clinical failure. However, among Crohn disease
      patients, a nonstricturing nonpenetrating phenotype was protective against ATI
      formation (OR 0.4, 95% CI 0.14-0.96, P = 0.04).Jewish Ashkenazi ethnicity is
      protective of ATI formation and infliximab therapy failure. These findings
      suggest a role for ethnicity, and implicitly for genetic predisposition, in
      modulating the risk of anti-TNF immunogenicity and treatment unresponsiveness. 

PMID- 25950683
TI  - Ethmoid osteoma as a culprit of orbital emphysema: a case report.
AB  - Orbital emphysema is generally recognized as a complication of orbital fractures
      involving any paranasal sinuses. The recognition about its etiology has extended
      beyond sole trauma, but few articles mentioned tumors to be a possible cause.In
      this case report, we present a patient with orbital emphysema associated with
      ethmoid osteoma without orbital cellulitis or trauma history. The patient
      developed sudden proptosis, eyelid swelling, and movement limitation of the left
      eye, peripheral diplopia, and left periorbital crepitus after a vigorous nose
      blowing.Complete surgical resection of ethmoid osteoma followed by repair of the
      orbital medial wall was performed with assistance of combined endoscopy and
      navigational techniques. Twelve-month follow-up showed no residual lesion or
      recurrence; the orbital medial wall was accurately repaired with good visual
      function and facial symmetry.Tumors should be considered for differential
      diagnosis of orbital emphysema, and combined endoscopy and navigational
      techniques may improve safety, accuracy, and effectiveness of orbital surgeries. 

PMID- 25950684
TI  - Can we clinically recognize a vascular depression? The role of personality in an
      expanded threshold model.
AB  - The vascular depression (VD) hypothesis postulates that cerebrovascular disease
      may "predispose, precipitate, or perpetuate" a depressive syndrome in elderly
      patients. Clinical presentation of VD has been shown to differ to major
      depression in quantitative disability; however, as little research has been made
      toward qualitative phenomenological differences in the personality aspects of the
      symptom profile, clinical diagnosis remains a challenge.We attempted to identify
      differences in clinical presentation between depression patients (n = 50) with (n
      = 25) and without (n = 25) vascular disease using questionnaires to assess
      depression, affect regulation, object relations, aggressiveness, alexithymia,
      personality functioning, personality traits, and counter transference.We were
      able to show that patients with vascular dysfunction and depression exhibit
      significantly higher aggressive and auto-aggressive tendencies due to a lower
      tolerance threshold. These data indicate that VD is a separate clinical entity
      and secondly that the role of personality itself may be a component of the
      disease process. We propose an expanded threshold disease model incorporating
      personality functioning and mood changes. Such findings might also aid the
      development of a screening program, by serving as differential criteria,
      ameliorating the diagnostic procedure. 

PMID- 25950685
TI  - When Planning Screw Fracture Fixation Why the 5.5 mm Screw is the Goldilocks
      Screw. An Observational Computer Tomographic Study of Fifth Metatarsal Bone
      Anatomy in a Sample of Patients.
AB  - We wanted to verify our clinical experience that the 5.5 mm screw was ideal in
      the majority of fifth metatarsal fracture fixation. The size of a screw is
      important for the successful surgical treatment of these fractures in order to
      obtain the maximal stability while reducing the risk for iatrogenic fracture.A
      sample of patients undergoing computer tomographic imaging of the foot for
      investigation other than fifth metatarsal pathology were recruited. The
      parameters of the fifth metatarsal bone anatomy were measured.These parameters of
      the 5.5 mm screw were correlated with this data. The upper parameter (the
      diameter of the threads) was 5.5 and the lower parameter (the diameter of the
      shank) was 4.0 mm.Twenty seven patients were recruited.The proximal third
      internal diameter ranged from 3.6 to 7.0 mm with a mean of 5.0 mm. 93% of the
      metatarsals could easily accommodate the 5.5 mm screw. Two of the metatarsals had
      an internal diameter of < 4 mm (7%).It is our belief that the 5.5 mm screw may be
      used safely in the majority of patients with fifth metatarsal fractures. 

PMID- 25950686
TI  - Nasopharyngeal and Adenoid Colonization by Haemophilus influenzae and Haemophilus
      parainfluenzae in Children Undergoing Adenoidectomy and the Ability of Bacterial
      Isolates to Biofilm Production.
AB  - Haemophili are pathogenic or opportunistic bacteria often colonizing the upper
      respiratory tract mucosa. The prevalence of Haemophilus influenzae (with
      serotypes distribution), and H. parainfluenzae in the nasopharynx and/or the
      adenoid core in children with recurrent pharyngotonsillitis undergoing
      adenoidectomy was assessed. Haemophili isolates were investigated for their
      ability to biofilm production.Nasopharyngeal swabs and the adenoid core were
      collected from 164 children who underwent adenoidectomy (2-5 years old). Bacteria
      were identified by the standard methods. Serotyping of H. influenzae was
      performed using polyclonal and monoclonal antisera. Biofilm formation was
      detected spectrophotometrically using 96-well microplates and 0.1% crystal
      violet.Ninety seven percent (159/164) children who underwent adenoidectomy were
      colonized by Haemophilus spp. The adenoid core was colonized in 99.4% (158/159)
      children, whereas the nasopharynx in 47.2% (75/159) children (P < 0.0001). In 32%
      (51/159) children only encapsulated (typeable) isolates of H. influenzae were
      identified, in 22.6% (36/159) children only (nonencapsulated) H. influenzae NTHi
      (nonencapsulated) isolates were present, whereas 7.5% (12/159) children were
      colonized by both types. 14.5% (23/159) children were colonized by untypeable
      (rough) H. influenzae. In 22% (35/159) children H. influenzae serotype d was
      isolated. Totally, 192 isolates of H. influenzae, 96 isolates of H.
      parainfluenzae and 14 isolates of other Haemophilus spp. were selected. In 20.1%
      (32/159) children 2 or 3 phenotypically different isolates of the same species
      (H. influenzae or H. parainfluenzae) or serotypes (H. influenzae) were identified
      in 1 child. 67.2% (129/192) isolates of H. influenzae, 56.3% (54/96) isolates of
      H. parainfluenzae and 85.7% (12/14) isolates of other Haemophilus spp. were
      positive for biofilm production. Statistically significant differences (P =
      0.0029) among H. parainfluenzae biofilm producers and nonproducers in the adenoid
      core and the nasopharynx were detected.H. influenzae and H. parainfluenzae
      carriage rate was comparatively higher in the adenoid core than that in the
      nasopharynx in children undergoing adenoidectomy, suggesting that their
      involvement in chronic adenoiditis. The growth in the biofilm seems to be an
      important feature of haemophili colonizing the upper respiratory tract
      responsible for their persistence.

PMID- 25950687
TI  - Factors affecting compliance with colorectal cancer screening among households
      residing in the largely Haitian community of Little Haiti, Miami-Dade County,
      Florida: an observational study.
AB  - The United States Black population is disproportionately affected by colorectal
      cancer (CRC) in terms of incidence and mortality. Studies suggest that screening
      rates are lower among Blacks compared with non-Hispanic Whites (NHWs). However,
      studies on CRC screening within Black subgroups are lacking. This study examined
      disparities in blood stool test (BST) compliance and colonoscopy use by
      race/ethnicity (Haitian, NHW, non-Hispanic Black [NHB], and Hispanic) among
      randomly selected households in Little Haiti, Miami-Dade County, Florida.This
      study used cross-sectional, health and wellness data from a random-sample,
      population-based survey conducted within 951 households in Little Haiti between
      November 2011 and December 2012. BST compliance and colonoscopy use were self
      reported and defined, conservatively, as the use of BST within the past 2 years
      and the ever use of colonoscopy by any household member. Factors associated with
      BST compliance and colonoscopy use were identified using logistic regression
      models. Analyses were restricted to households containing at least 1 member >=50
      years (n = 666).Nearly half of the households were compliant with BST (rate [95%
      confidence interval (CI)] = 45% [41%-49%]) and completed colonoscopy (rate [95%
      CI] = 53% [49%-58%]). Compliance with BST was not associated with race/ethnicity
      (P = 0.76). Factors independently associated with BST compliance included low
      educational attainment (adjusted odds ratio [AOR] = 0.63, P = 0.03), being single
      (AOR = 0.47, P = 0.004), retirement (AOR = 1.96, P = 0.01), and the presence of
      diagnosed health problems (AOR = 1.24, P = 0.01). Colonoscopy use was lower among
      Haitian households (46%) compared with NHW (63%), NHB (62%), and Hispanic
      households (54%) (P = 0.002). Factors independently associated with colonoscopy
      use included identifying as NHB (compared with Haitian) (AOR = 1.80, P = 0.05),
      being single (AOR = 0.44, P = 0.001), retirement (AOR = 1.86, P = 0.02), lack of
      continuous insurance (AOR = 0.45, P < 0.001), and the presence of diagnosed
      health problems (AOR = 1.44, P < 0.001) and physical limitations/disabilities
      (AOR = 1.88, P = 0.05).Compliance with BST and use of colonoscopy are low within
      households in the Little Haiti community. Significant disparities in the use of
      colonoscopy exist between Haitian and NHB households. Barriers and facilitators
      of colonoscopy within each racial/ethnic group need to be identified as the next
      step to developing culturally appropriate, community-based interventions aimed at
      increasing colonoscopy use in this large minority population. 

PMID- 25950689
TI  - Vitamin D supplementation: we must not fail our children!
AB  - There is increasing concern that vitamin D deficiency poses a major health
      problem for children. Deficiency can cause hypocalcemic seizures, growth
      disturbances, and rickets and may influence diabetes, cardiovascular dysfunction,
      autoimmune diseases, and attention deficit hyperactivity disorders. Reduced
      vitamin D levels in children presenting to pediatric orthopedic services are
      common.In the United Kingdom, recommendations on vitamin D supplementation are
      set by the Department of Health (DoH) and the National Institute of Health and
      Clinical Excellence. These state that all children aged 6 months to 5 years ought
      to receive 7 to 8.5 MUg of vitamin D daily.We carried out a survey of 203 parents
      attending our pediatric and pediatric orthopedic and fracture clinics to evaluate
      parental awareness of the DoH recommendations on vitamin D supplementation for
      children and to assess the extent to which children were receiving vitamin D
      supplements.About 85.71% of parents were not aware of the recommendations. Only
      14.29% stated that they were aware of the benefits of vitamin D for their
      children and just 17.73% of children were receiving vitamin D supplementation; 17
      via formula milk and 18 via multivitamin formulations.Parents are generally not
      aware about vitamin D supplementation because of a lack of information with the
      high rates of reported suboptimal vitamin D levels amongst children not being
      addressed resulting in increased health risks to our children. Major improvements
      are needed in the implementation of supplementation at all points of contact
      between parents and health-care professionals.

PMID- 25950688
TI  - Anesthetic influence on occurrence and treatment of the trigemino-cardiac reflex:
      a systematic literature review.
AB  - Trigeminocardiac reflex (TCR) is defined as sudden onset of parasympathetic
      dysrhythmia including hypotension, apnea, and gastric hypermotility during
      stimulation of any branches of the trigeminal nerve. Previous publications imply
      a relation between TCR and depth of anesthesia. To gain more detailed insights
      into this hypothesis, we performed a systematic literature review.Literature
      about occurrence of TCR was systematically identified through searching in
      Cochrane Central Register of Controlled Trials (CENTRAL), PubMed (MEDLINE),
      EMBASE (Ovid SP), and the Institute for Scientific Information (ISI Web of
      Sciences) databases until June 2013, as well as reference lists of articles for
      risk calculation. In this study, TCR was defined as drop in mean arterial blood
      pressure and heart rate, both >20% to baseline. We calculated intraoperative
      cerebral state index (CSI) of each TCR-case using a newly developed method. These
      data were further divided into 3 subgroups: CSI <40 (deep anesthesia), CSI 40-60
      (regular anesthesia), and CSI >60 (slight anesthesia).Including 45 studies with
      910 patients, 140 (15%) presented with TCR, and 770 (85%) without TCR during
      operation. TCR occurrence showed a 1.2-fold higher pooled risk slighter
      anesthesia (CSI <40: 13%, at CSI 40-60: 21%, and at CSI >60: 27%) compared with
      deeper anesthesia. In addition, we could discover a 1.3-fold higher pooled risk
      of higher MABP drop with a strong negative correlation (r = -0.935; r = 0.89) and
      a 4.5-fold higher pooled risk of asystole during TCR under slight anesthesia
      compared with deeper anesthesia.Our work is the first systematic review about TCR
      and demonstrates clear evidence for TCR occurrence and a more severe course of
      the TCR in slight anesthesia underlying the importance of skills in anesthesia
      management during skull base surgery. Furthermore, we have introduced a new
      standard method to calculate the depth of anesthesia. 

PMID- 25950690
TI  - Positron Emission Tomography With 18F-Fluorodeoxyglucose in Patients With Sickle
      Cell Acute Chest Syndrome.
AB  - The acute chest syndrome (ACS) is the main cause of mortality among adult
      patients with sickle cell disease (SCD). Its pathophysiology is still unclear.
      Using positron emission tomography (PET) with F-fluorodeoxyglucose [18F
      fluorodeoxyglucose (F-FDG)], we explored the relationship between regional lung
      density and lung metabolism, as a reflection of lung neutrophilic infiltration
      during ACS.Patients were prospectively enrolled in a single-center study. Dual
      modality chest PET/computed tomography (CT) scans were performed, with F-FDG
      emission scans for quantification of regional F-FDG uptake and CT scans with
      radiocontrast agent to check for pulmonary artery thrombosis. Regional lung F-FDG
      uptake was quantified in ACS patients and in SCD patients without ACS (SCD non
      ACS controls). Maximal (SUVmax) and mean (SUVmean) standardized uptake values
      were computed.Seventeen patients with ACS (mean age 28.3 +/- 6.4 years) were
      included. None died nor required invasive mechanical ventilation. The main lung
      opacity on CT scans was lower lobe consolidation. Lungs of patients with ACS
      exhibited higher SUVmax than those of SCD non-ACS controls (2.5 [2.1-2.9] vs 0.8
      [0.6-1.0]; P < 0.0001). Regional SUVmax and SUVmean was higher in lower than in
      upper lobes of ACS patients (P < 0.001) with a significant correlation between
      lung density and SUVmax (R = 0.78). SUVmean was higher in upper lobes of ACS
      patients than in lungs of SCD non-ACS controls (P < 0.001). Patients with SUVmax
      >2.5 had longer intensive care unit (ICU) stay than others (7 [6-11] vs 4 [3-6]
      days; P = 0.016).Lungs of patients with ACS exhibited higher F-FDG uptake than
      SCD non-ACS controls. Lung apices had normal aeration and lower F-FDG uptake than
      lung bases, but higher F-FDG uptake than lungs of SCD non-ACS controls. Patients
      with higher lung F-FDG uptake had longer ICU stay than others. 

PMID- 25950691
TI  - Nonsteroidal Anti-inflammatory Drugs as Prophylaxis for Heterotopic Ossification
      after Total Hip Arthroplasty: A Systematic Review and Meta-Analysis.
AB  - Heterotopic ossification (HO) is a frequent complication after total hip
      arthroplasty (THA). Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used
      as routine prophylaxis for HO after THA. However, the efficacy of NSAIDs on HO,
      particularly selective NSAIDs versus nonselective NSAIDs, is uncertain.We
      searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, and
      clinicaltrials.gov to identify randomized controlled trials with respect to HO
      after THA. Two reviewers extracted the data and estimated the risk of bias. For
      the ordered data, we followed the Bayesian framework to calculate the odds ratio
      (OR) with a 95% credible interval (CrI). For the dichotomous data, the OR and 95%
      confidence interval (CI) were calculated using Stata version 12.0. The subgroup
      analyses and the Grading of Recommendations, Assessment, Development and
      Evaluation (GRADE) approach were used.A total of 1856 articles were identified,
      and 21 studies (5995 patients) were included. In the NSAIDs versus placebo
      analysis, NSAIDs could decrease the incidence of HO, according to the Brooker
      scale (OR = 2.786, 95% CrI 1.879-3.993) and Delee scale (OR = 9.987, 95% CrI
      5.592-16.17). In the selective NSAIDs versus nonselective NSAIDs analysis, there
      was no significant difference (OR = 0.7989, 95% CrI 0.5506-1.125) in the
      prevention of HO. NSAIDs could increase discontinuation caused by
      gastrointestinal side effects (DGSE) (OR = 1.28, 95% CI 1.00-1.63, P = 0.046)
      more than a placebo. Selective NSAIDs could decrease DGSE (OR = 0.48, 95% CI 0.24
      0.97, P = 0.042) compared with the nonselective NSAIDs. There was no significant
      difference with respect to discontinuation caused by non-gastrointestinal side
      effects (DNGSE) in NSAIDs versus a placebo (OR = 1.16, 95% CI 0.88-1.53, P =
      0.297) and in selective NSAIDs versus nonselective NSAIDs (OR = 0.83, 95% CI 0.50
      1.37, P = 0.462).NSAIDs might reduce the incidence of HO and increase DGSE in the
      short-term.

PMID- 25950692
TI  - Why the Proximal Splenic Artery Approach is the Ideal Approach for Laparoscopic
      Suprapancreatic Lymph Node Dissection in Advanced Gastric Cancer? A Large-Scale
      Vascular-Anatomical-Based Study.
AB  - Laparoscopic gastrectomy with D2 lymph node (LN) dissection has not yet been
      widely adopted for advanced gastric cancer because it is technically complicated.
      Due to the high suprapancreatic lymph nodes metastasis rate (LMR) and the various
      vascular anatomies, the suprapancreatic LN dissection is a crucial and demanding
      procedure for radical resection of gastric cancer.To explore the anatomical basis
      of the proximal splenic artery (SA) approach for laparoscopic suprapancreatic LN
      dissection and its application in advanced gastric cancer.Laparoscopic
      suprapancreatic LN dissections were performed in 1551 consecutive advanced
      gastric cancer patients between June 2007 and November 2013. A total of 994
      consecutive patients since January 2011 were selected to compare the
      clinicopathological characteristics and surgical outcomes between the
      conventional approach group (330) and the proximal SA approach group (664). In
      the proximal SA approach, the No. 11p LNs are dissected first, followed by the
      Nos. 9, 7, and 8a LNs; dissection of the Nos. 5 and 12a LNs is performed last.In
      the suprapancreatic arteries, the proximal SA had the lowest anatomic variation
      rate (P < 0.05, each) and maximum diameter (P < 0.05, each) compared with the
      common hepatic artery (CHA), left gastric artery (LGA), right gastric artery
      (RGA), and gastroduodenal artery (GDA). In addition, the proximal SA was located
      closer to the suprapancreatic border than the CHA (P = 0.000). The No. 11p LMR
      was lower than the Nos. 9, 7, 8a, 5, and 12a LMR (P < 0.01, each). Compared with
      the conventional approach, the proximal SA approach was associated with less
      blood loss (P < 0.05), significantly more retrieved total LNs and suprapancreatic
      LNs (P < 0.01, each).The proximal SA exhibits the most constant and maximum
      diameter, is located closer to the suprapancreatic border, and exhibits the
      lowest LMR; therefore, the proximal SA approach is the ideal approach for
      laparoscopic suprapancreatic LN dissection in advanced gastric cancer. 

PMID- 25950693
TI  - Non-Hodgkin's Lymphoma of Multiple Skeletal Muscles Involvement Seen on FDG
      PET/CT Scans.
AB  - As normal healthy skeletal muscle does not contain lymphoid tissue, extra nodal
      lymphoma involving multiple muscles is rare, as well. This study reports a case
      of non-Hodgkin's lymphoma (NHL) of multiple skeletal muscles involvement and a
      review of differential diagnosis of it.A 37-year-old female presented to our
      hospital after being diagnosed with NHL for 7 months. She had received six
      courses of cyclophosphamide hydroxydaunorubicin oncovin prednisolone etoposide
      (CHOPE) chemotherapy. Then she felt pain and noticed swelling on her left calf.
      The fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed
      tomography (CT) image showed abnormal focal FDG uptake in hypo-pharynx, which was
      the primary NHL and also in multiple groups of muscles in whole body. As the
      patient has history NHL, lymphoma of multiple muscle involvement was
      suspected.Finally, an ultrasound-guided tissue biopsy was performed on the left
      calf and histological examination yielded lymphomatous cells infiltration in the
      left gastrocnemius.Through this report, we emphasize that a multidisciplinary
      team approach with clinician, radiologist, and pathologist is essential for
      proper diagnosis, staging, and management of such rare lesions. 

PMID- 25950694
TI  - Global positioning system use in the community to evaluate improvements in
      walking after revascularization: a prospective multicenter study with 6-month
      follow-up in patients with peripheral arterial disease.
AB  - Revascularization aims at improving walking ability in patients with arterial
      claudication. The highest measured distance between 2 stops (highest-MDCW), the
      average walking speed (average-WSCW), and the average stop duration (average
      DSCW) can be measured by global positioning system, but their evolution after
      revascularization is unknown.We included 251 peripheral artery diseased patients
      with self-reported limiting claudication. The patients performed a 1-hour stroll,
      recorded by a global positioning system receiver. Patients (n = 172) with
      confirmed limitation (highest-MDCW <2000m) at inclusion were reevaluated after 6
      months. Patients revascularized during the follow-up period were compared with
      reference patients (ie, with unchanged lifestyle medical or surgical status).
      Other patients (lost to follow-up or treatment change) were excluded (n = 89).We
      studied 44 revascularized and 39 reference patients. Changes in highest-MDCW
      (+442 vs. +13 m) and average-WSCW (+0.3 vs. -0.2 km h) were greater in
      revascularized than in reference patients (both P < 0.01). In contrast, no
      significant difference in average-DSCW changes was found between the groups.
      Among the revascularized patients, 13 (29.5%) had a change in average-WSCW, but
      not in highest-MDCW, greater than the mean + 1 standard deviation of the change
      observed for reference patients.Revascularization may improve highest-MDCW and/or
      average-WSCW. This first report of changes in community walking ability in
      revascularized patients suggests that, beyond measuring walking distances,
      average-WSCW measurement is essential to monitor these changes. Applicability to
      other surgical populations remains to be evaluated. REGISTRATION:
      http://www.clinicaltrials.gov/ct2/show/NCT01141361.

PMID- 25950695
TI  - The CD4 Lymphocyte Count is a Better Predictor of Overall Infection Than the
      Total Lymphocyte Count in ANCA-Associated Vasculitis Under a Corticosteroid and
      Cyclophosphamide Regimen: A Retrospective Cohort.
AB  - Patients with antineutrophil cytoplasmic autoantibody associated vasculitis (AAV)
      have a high prevalence of infection during immunosuppressive therapy, and the
      total lymphocyte count (TLC) has been demonstrated to be an independent predictor
      of infection. The current study investigated the value of the TLC and its
      subsets, particularly the CD4 count, for predicting infections of AAV in a single
      Chinese cohort.A total of 124 AAV patients were retrospectively recruited in our
      department from December 1997 to October 2013. Multivariate Cox models with the
      CD4 count or TLC measured at three typical time points, that is, at baseline, at
      the beginning of immunosuppressant dose reduction, and at the last visit before
      infection or censoring, or with the measurements included as time-varying
      covariates, were compared to select the most predictive time point for infection.
      A time-dependent area under the receiver operating characteristic curve (AUC(t))
      for the TLC (AUC(t)TLC) and the CD4 count (AUC(t)CD4count) measured at the most
      predictive time point were calculated and compared.During an average follow-up of
      11.5 (range 0.5-142) months, 55 of the 124 patients (44.3%) experienced a
      microbiologically confirmed infection. Independent predictors of overall
      infection were initial creatinine clearance (P = 0.02 and 0.04), pulmonary
      interstitial fibrosis (P = .04 and .05), pulmonary nodule or cavity (P = 0.002
      and .002), CD4 count (P < 0.001) or TLC (P = 0.05) from the last visit. The
      comparison of Cox models fitted at different time points confirmed the last visit
      to be the most predictive one for overall infection. The predictive value of the
      CD4 count or TLC from the last visit measured by AUC showed that the
      AUC(t)CD4count (62.8-70.2%) was almost always higher than AUC(t)TLC (55.2-58.1%)
      during the first 2 years of immunosuppressive therapy (P = 0.01-0.2). In terms of
      different pathogens, both the CD4 count and TLC performed well for non-bacterial
      infection (AUC(t) 69.2-82.7%), and the difference between them was not
      significant (P > 0.1).The TLC and CD4 count were both independent risk factors of
      overall infection and non-bacterial infection in AAV patients. The CD4 count had
      a higher predictive value than the TLC for overall infections, particularly
      during the first 2 years of immunosuppressive therapy. 

PMID- 25950696
TI  - Clinical significance of preoperative serum high density lipoprotein cholesterol
      levels in soft tissue sarcoma.
AB  - The prognostic value of lipid profile remains unclear in soft tissue sarcoma. The
      aim of the present study was to validate the prognostic value of preoperative
      plasma lipid profile (high density lipoprotein-cholesterol [HDL-C], low density
      lipoprotein-cholesterol [LDL-C], cholesterol, and triglycerides) levels on
      disease-free survival (DFS) and overall survival (OS) in soft tissue sarcoma
      (STS) patients undergoing extensive and radical surgical resection.The
      preoperative plasma lipid profile levels of 234 STS patients, who were operated
      on between 2000 with 2010, were retrospectively evaluated. Kaplan-Meier curves
      and multivariate Cox proportional models were calculated for DFS and OS.In
      univariate analysis, a decreased HDL-C level was significantly associated with
      decreased OS (hazard ratio [HR], 3.405; 95% confidence interval (CI), 1.445
      8.021, P = 0.005) and remained significant in the multivariate analysis (HR,
      5.615; 95% CI, 1.243-25.378, P = 0.025). Patients with HDL-C < 1.475 mmol/L
      showed a median OS of 71 months. In contrast, patients with HDL-C >=1.475 mmol/L
      had a median OS of 101 months. In univariate analysis, a decreased HDL-C level
      was significantly associated with decreased DFS (HR, 2.085; 95% CI, 1.271-3.422,
      P = 0.004) and remained significant in the multivariate analysis (HR, 1.808; 95%
      CI, 1.118-2.924, P = 0.016). Patients with HDL-C <1.475 mmol/L presented with a
      median DFS of 47 months, whereas patients with HDL-C >=1.475 mmol/L had a median
      DFS of 78 months. In univariate analysis and multivariate analyses regarding OS
      and DFS, there was no significant association between the groups in terms of LDL
      C, CHO and TG.Our study investigated the potential prognostic utility of
      preoperative plasma HDL-C levels as an independent factor in STS patients who had
      undergone radical surgical resection. 

PMID- 25950697
TI  - Estimating cardiac substructures exposure from diverse radiotherapy techniques in
      treating left-sided breast cancer.
AB  - The study compares the physical and biologically effective doses (BED) received
      by the heart and cardiac substructures using three-dimensional conformal RT (3D
      CRT), intensity-modulated radiotherapy (IMRT), and simple IMRT (s-IMRT) in
      postoperative radiotherapy for patients with left-sided breast cancer. From
      October 2008 to February 2009, 14 patients with histologically confirmed left
      sided breast cancer were enrolled and underwent contrast-enhanced computed
      tomography (CT) simulation and 18F-FDG positron emission tomography-CT to outline
      the left cardiac ventricle (LV) and other substructures. The linear-quadratic
      model was used to convert the physical doses received by critical points of inner
      heart to BED.The maximal dose, minimum dose, dose received by 99% of volume (D99)
      and dose received by 95% of volume (D95) in target areas were significantly
      better using IMRT and s-IMRT when compared with 3D-CRT (P < 0.05). IMRT and s
      IMRT significantly reduced the maximal cardiac dose (5038.98 vs 5346.47 cGy, P =
      0.002; 5146.66 vs 5346.47 cGy, P = 0.03). IMRT reduced the maximal dose to LV by
      4% (P = 0.05) in comparison with 3D-CRT. The average doses to heart and LV in 3D
      CRT plan were significantly lower than those in IMRT plan (P < 0.05). The average
      cardiac volumes receiving >=25 Gy (V25 Gy) in IMRT, s-IMRT, and 3D-CRT plans were
      73.98, 76.75, and 60.34 cm, respectively. The average LV volumes receiving >=25
      Gy (V25 Gy) in IMRT, s-IMRT and 3D-CRT plans were 23.37, 24.68, and 17.61 cm,
      respectively. In the IMRT plan, the mean BED to the critical points of inner
      heart located within the high physical dose area were substantially lower than in
      3D-CRT or s-IMRT.Compared with 3D-CRT technique, IMRT and s-IMRT had superior
      target dose coverage and dose uniformity. IMRT significantly reduced the maximal
      RT dose to heart and LV. IMRT and s-IMRT techniques did not reduce the volume of
      heart and LV receiving high doses.

PMID- 25950698
TI  - High-intensity focused ultrasound combined with suction curettage for the
      treatment of cesarean scar pregnancy.
AB  - The aim of this study was to retrospectively evaluate the safety and feasibility
      of high-intensity focused ultrasound (HIFU) treatment combined with suction
      curettage under hysteroscopic guidance for cesarean scar pregnancy (CSP).Fifty
      three patients with definite CSP were treated with HIFU followed by suction
      curettage under hysteroscopic guidance. All the patients received 1 session of
      HIFU ablation under conscious sedation. Suction curettage under hysteroscopic
      guidance was performed at an average of 2.9 (range: 1-5) days after HIFU
      ablation. Blood flow of pregnancy tissue before and after HIFU, intraoperative
      blood loss in suction curettage and hysteroscopy procedure, time for beta-human
      chorionic gonadotropin (beta-hCG) to return to normal level, and time for normal
      menstruation recovery were recorded.Immediately after HIFU treatment, color
      Doppler ultrasound showed that the fetal cardiac activity disappeared and the
      blood flow in the pregnancy tissue significantly decreased. All the patients
      underwent suction curettage under hysteroscopic guidance after the treatment of
      HIFU, the median volume of blood loss in the procedure was 20 mL (range: 10-400
      mL). The average time for menstruation recovery was 35.1 +/- 8.1 (range: 19-60)
      days. The average time needed for serum beta-hCG to return to normal levels was
      27.5 +/- 6.4 (range: 12-40) days. The average hospital stay was 7.8 +/- 1.5
      (range: 5-11) days.Based on our results, it appears that HIFU combined with
      suction curettage under hysteroscopic guidance is safe and effective in treating
      patients with CSP at gestational ages <8 weeks. 

PMID- 25950699
TI  - Incidence and risk factors for retinopathy of prematurity in multiple gestations:
      a Chinese population study.
AB  - To determine the incidence and risk factors of retinopathy of prematurity (ROP)
      among new-born Chinese infants of multiple gestations.A retrospective review of
      medical records was performed for all neonates of multiple gestations screened
      for ROP between January 2007 and December 2012 in 2 neonatal intensive care units
      in Hong Kong. Screening was offered to very low birth weight (VLBW; <=1500 g)
      and/or preterm (gestation <=32 weeks) neonates using the Royal College of
      Ophthalmologists ROP guideline and the International Classification of ROP by 3
      pediatric ophthalmologists. Maternal and neonatal covariates were analyzed using
      univariate and multivariate regression analyses for both ROP and Type 1 ROP.A
      total of 153 Chinese infants of multiple gestations were included in the study.
      The mean gestational age (GA) was 30.8 +/- 2.4 weeks and the mean birth weight
      (BW) was 1284.8 +/- 267.4 g. The incidence of ROP and Type 1 ROP was 11.8% and
      3.9%, respectively. On univariate analysis, younger GA, lighter birth weight,
      postnatal hypotension, inotropes use, bronchopulmonary disease, and
      intraventricular hemorrhage were common independent risk factors for the
      development of ROP and Type 1 ROP (all P <= 0.04). On multivariate analysis,
      younger GA, surfactant use, invasive mechanical ventilation, higher mean oxygen
      concentration, thrombocytopenia, intraventricular hemorrhage, total parental
      nutrition, and hypoglycemia were significant risk factors for ROP. For Type 1
      ROP, there were no significant dependent risk factors.In preterm Chinese infants
      born from multiple gestations, prematurity, lighter weight, postnatal
      hypotension, inotropes use, bronchopulmonary dysplasia, and an intraventricular
      hemorrhage were common independent risk factors for the development of ROP and
      Type 1 ROP.

PMID- 25950700
TI  - Canine length in wild male baboons: maturation, aging and social dominance rank.
AB  - Canines represent an essential component of the dentition for any heterodont
      mammal. In primates, like many other mammals, canines are frequently used as
      weapons. Hence, tooth size and wear may have significant implications for
      fighting ability, and consequently for social dominance rank, reproductive
      success, and fitness. We evaluated sources of variance in canine growth and
      length in a well-studied wild primate population because of the potential
      importance of canines for male reproductive success in many primates.
      Specifically, we measured maxillary canine length in 80 wild male baboons (aged
      5.04-20.45 years) from the Amboseli ecosystem in southern Kenya, and examined its
      relationship with maturation, age, and social dominance rank. In our analysis of
      maturation, we compared food-enhanced baboons (those that fed part time at a
      refuse pit associated with a tourist lodge) with wild-feeding males, and found
      that food-enhanced males achieved long canines earlier than wild-feeding males.
      Among adult males, canine length decreased with age because of tooth wear. We
      found some evidence that, after controlling for age, longer canines were
      associated with higher adult dominance rank (accounting for 9% of the variance in
      rank), but only among relatively high-ranking males. This result supports the
      idea that social rank, and thus reproductive success and fitness, may depend in
      part on fighting ability mediated by canine size. 

PMID- 25950701
TI  - TNF-alpha Producing Innate Lymphoid Cells (ILCs) Are Increased in Active Celiac
      Disease and Contribute to Promote Intestinal Atrophy in Mice.
AB  - Innate lymphoid cells (ILCs) are an emerging family of innate hematopoietic cells
      producing inflammatory cytokines and involved in the pathogenesis of several
      immune-mediated diseases. The aim of this study was to characterize the tissue
      distribution of ILCs in celiac disease (CD), a gluten-driven enteropathy, and
      analyze their role in gut tissue damage. ILC subpopulations were analyzed in
      lamina propria mononuclear cells (LPMCs) isolated from duodenal biopsies of CD
      patients and healthy controls (CTR) and jejunal specimens of patients undergoing
      gastro-intestinal bypass by flow cytometry. Cytokines and Toll-like receptors
      (TLR) were assessed in ILCs either freshly isolated or following incubation of
      control LPMC with peptidoglycan, poly I:C, or CpG, the agonists of TLR2, TLR3, or
      TLR9 respectively, by flow cytometry. The role of ILCs in gut tissue damage was
      evaluated in a mouse model of poly I:C-driven small intestine atrophy. Although
      the percentage of total ILCs did not differ between CD patients and CTR, ILCs
      producing TNF-alpha and IFN-gamma were more abundant in CD mucosa compared to
      controls. ILCs expressed TLR2, TLR3 and TLR9 but neither TLR7 nor TLR4.
      Stimulation of LPMC with poly I:C but not PGN or CpG increased TNF-alpha and IFN
      gamma in ILCs. RAG1-deficient mice given poly I:C exhibited increased frequency
      of TNF-alpha but not IFN-gamma/IL17A-producing ILCs in the gut and depletion of
      ILCs prevented the poly I:C-driven intestinal damage. Our data indicate that CD
      related inflammation is marked by accumulation of ILCs producing TNF-alpha and
      IFN-gamma in the mucosa. Moreover, ILCs express TLR3 and are functionally able to
      respond to poly I:C with increased synthesis of TNF-alpha thus contributing to
      small intestinal atrophy. 

PMID- 25950703
TI  - Framework for advanced nursing, midwifery and allied health professional practice
      in Wales: the implementation process.
AB  - AIM: To discuss the implementation of the Welsh Government's Advanced Practice
      Framework into a Welsh University Health Board. BACKGROUND: A plethora of
      advanced practice roles have evolved across all health-care areas in response to
      the European Working Time Directive and workforce shortage drivers, leading to
      confusion and lack of structure. EVALUATION: A literature review was undertaken
      and a staged plan implemented. Data presented as descriptive statistics and
      graphs include staff numbers, grade, educational qualifications job plans and
      funding streams. KEY ISSUES: Advanced practice should be viewed as a level of
      practice and not as a role. It must be underpinned by robust Governance
      arrangements and included in workforce planning. Audit of practice demonstrates
      the impact of advanced practice roles in the delivery of high quality safe
      patient care. CONCLUSIONS: The Advanced Practice Framework will ensure
      consistency in clinical practice skills and theoretical knowledge of
      practitioners holding the protected title. It will support organisations to
      deliver high quality responsive services. IMPLICATIONS FOR NURSING MANAGEMENT:
      Health-care delivery continues to evolve rapidly with advanced practice forming
      part of the future delivery model of flexible and affordable services, whilst
      ensuring safe, high quality patient care. It also provides a clear career
      development structure.

PMID- 25950702
TI  - Depression and posttraumatic stress disorder among women with vulvodynia:
      evidence from the population-based woman to woman health study.
AB  - BACKGROUND: Psychological disorders may affect the pain experience of women with
      vulvodynia, but evidence remains limited. The present study aimed to describe the
      magnitude of the association of depression and posttraumautic stress disorder
      (PTSD) with the presence of vulvodynia in a nonclinical population from
      southeastern Michigan. METHODS: Baseline data from 1,795 women participating in
      the Woman to Woman Health Study, a multiethnic population-based study, was used
      for this analysis. Validated screening questionnaires were conducted to assess
      vulvodynia, depression, and PTSD. Modified Poisson regression models with a
      robust variance estimation were used to estimate prevalence ratios (PR) and their
      95% confidence intervals (CI) for the association between vulvodynia status and
      two mental health conditions, depression and PTSD. RESULTS: In the adjusted
      models, women who screened positive for depression had a 53% higher prevalence of
      having vulvodynia (PR=1.53; 95% CI: 1.12, 2.10) compared with women who screened
      negative for depression. Women who screened positive for PTSD had more than a two
      fold increase in the prevalence of having vulvodynia (PR=2.37; 95% CI: 1.07,
      5.25) compared with women who screened negative for PTSD. CONCLUSIONS: The
      increased prevalence of vulvodynia among those screening positive for depression
      or PTSD suggests that these disorders may contribute to the likelihood of
      reporting vulvodynia. Alternatively, vulvodynia, depression, and PTSD may have a
      common pathophysiological and risk profile. Prospective studies are needed to
      improve our understanding of the temporal relation between mental health
      conditions and vulvar pain.

PMID- 25950704
TI  - Relocalisation and activation of integrins induced rapidly by oestrogen via G
      protein-coupled receptor 30 in mouse blastocysts.
AB  - Integrins are the dominant and final adhesion molecules in the attachment process
      between the blastocysts and endometrium. It is necessary for oestrogen to rapidly
      activate mouse blastocysts so that they attach to the endometrial epithelium. Our
      previous study suggested that oestrogen can rapidly induce an increase in
      intracellular calcium in mouse blastocysts via G-protein-coupled receptor 30
      (GPR30). Thus, we deduced that integrins may be involved in GPR30 mediation of
      the fast effect of oestrogen on mouse blastocysts in implantation. To prove our
      hypothesis, we used immunofluorescence staining and in vitro coculture of mouse
      blastocysts and endometrial epithelial cell line (EECs), Ishikawa cells, in the
      present study. We found that alphav and beta1 integrin clustered in mouse
      blastocysts, and that beta3 integrin was relocalised to the apical membrane of
      blastocyst cells when embryos were treated with 1 MUM 17beta-estradiol (E2), 1
      MUM E2 conjugated to bovine serum albumin (E2-BSA) and 1 MUM G-1, a specific
      GPR30 agonist, for 30 min respectively, whereas pretreatment with 1 MUM G15, a
      specific GPR30 antagonist, and 5 MUM 1,2-Bis(2-aminophenoxy)ethane-N,N,N'',N''
      tetraacetic acid tetrakis (acetoxymethyl ester)(BAPTA/AM), a cellular Ca2+
      chelator, blocked the localisation of integrins induced by oestrogen via GPR30 in
      mouse blastocyst cells. E2, E2-BSA and G-1 increased the fibronectin (FN)-binding
      activity of integrins in blastocysts, whereas G15 and BAPTA/AM blocked the
      activation of integrins induced by oestrogen via GPR30 in mouse blastocysts.
      Inhibition of integrins by Arg-Gly-Asp peptide in blastocysts resulted in their
      failure to adhere to EECs in vitro, even if oestrogen or G-1 was provided.
      Together, the results indicate the fast effect of oestrogen via the GPR30
      membrane receptor further induces relocalisation and activation of integrins in
      mouse blastocysts, which play important roles in the adhesion of blastocysts to
      EECs.

PMID- 25950705
TI  - Correction: Transplantation of Adult Mouse iPS Cell-Derived Photoreceptor
      Precursors Restores Retinal Structure and Function in Degenerative Mice.

PMID- 25950706
TI  - Homozygous autosomal dominant hypercholesterolaemia: prevalence, diagnosis, and
      current and future treatment perspectives.
AB  - PURPOSE OF REVIEW: Homozygous autosomal dominant hypercholesterolemia (hoADH) is
      a rare genetic disorder caused by mutations in LDL receptor, apolipoprotein B,
      and/or proprotein convertase subtilisin-kexin type 9. Both the genetic mutations
      and the clinical phenotype vary largely among individual patients, but patients
      with hoADH are typically characterized by extremely elevated LDL-cholesterol (LDL
      C) levels, and a very high-risk for premature cardiovascular disease. Current
      lipid-lowering therapies include bile acid sequestrants, statins, and ezetimibe.
      To further decrease LDL-C levels in hoADH, lipoprotein apheresis is recommended,
      but this therapy is not available in all countries. RECENT FINDINGS: Recently,
      the microsomal triglyceride transfer protein inhibitor lomitapide and the RNA
      antisense inhibitor of apolipoprotein B mipomersen were approved by the Food and
      Drug Administration/European Medicine Agency and the Food and Drug
      Administration, respectively. Several other LDL-C-lowering strategies and
      therapeutics targeting the HDL-C pathway are currently in the clinical stage of
      development. SUMMARY: Novel therapies have been introduced for LDL-C-lowering and
      innovative drug candidates for HDL-C modulation for the treatment of hoADH. Here,
      we review the current available literature on the prevalence, diagnosis, and
      therapeutic strategies for hoADH.

PMID- 25950707
TI  - Designing dietary patterns to minimize overall disease burden.

PMID- 25950708
TI  - Regulation of lipid metabolism by microRNAs.

PMID- 25950709
TI  - Atherosclerosis: cell biology and lipoproteins-focus on CD40 signaling, PCSK9,
      and novel animal models.

PMID- 25950711
TI  - Misconceptions about smoking in patients with type 2 diabetes mellitus: a
      qualitative analysis.
AB  - AIMS AND OBJECTIVES: To investigate the smoking behaviours, perceptions about
      quitting smoking and factors associated with intention to quit in patients with
      type 2 diabetes mellitus. BACKGROUND: Smoking causes type 2 diabetes mellitus.
      There has been limited research on the needs and concerns of smokers with type 2
      diabetes mellitus about quitting smoking. DESIGN: The study used a qualitative
      design. METHODS: Patients diagnosed with type 2 diabetes mellitus who had a
      history of smoking were recruited at the outpatient diabetic clinics of two major
      local hospitals in Hong Kong for a semi-structured interview (n = 42), guided by
      the theory of planned behaviour. RESULTS: At data saturation, 22 current smokers
      and 20 ex-smokers with type 2 diabetes mellitus were recruited. The current
      smokers reported they had not quit smoking because of satisfaction with present
      health status, and misconceptions about the association between diabetes and
      smoking, and the perceived hazards of quitting. In contrast, ex-smokers had a
      positive opinion about quitting smoking, accepted advice about quitting from
      health professionals and received more family support than current smokers.
      Psychological addiction and weight gain after cessation made quitting
      challenging. CONCLUSIONS: Satisfaction with health status, inadequate knowledge
      about the relationship between type 2 diabetes mellitus and smoking, and
      misconceptions about quitting smoking resulted in negative attitudes toward
      quitting by type 2 diabetes mellitus smokers. Smoking peers, psychological
      addiction and post-cessation weight gain hindered the quitting process. RELEVANCE
      TO CLINICAL PRACTICE: Education on the causal link between smoking, type 2
      diabetes mellitus and its complications is important to raise health awareness
      and counter misconceptions about quitting smoking. Behavioural counselling with
      weight control strategies should be part of a comprehensive smoking cessation
      intervention for type 2 diabetes mellitus smokers.

PMID- 25950712
TI  - Histopathology of rhinophyma - a clinical-histopathologic correlation.
AB  - BACKGROUND: Whereas early rhinophyma is histopathologically thought to resemble
      fully developed rosacea, a fibromatous variant has previously been described for
      severe rhinophyma. In terms of clinical characteristics, recently a new
      Rhinophyma Severity Index (RHISI) was introduced. METHODS: We studied 24 patients
      who had been treated with wide shave excisions for rhinophyma. Specimens were
      stained with hematoxylin-eosin, periodic acid-Schiff reaction and a panel of
      immunohistochemical stains and observed for any correlation between clinical
      severity and histopathologic features as well as for predictive markers of
      clinical recurrence. RESULTS: There were no significant histopathologic
      differences between the groups reflecting the different clinical expressions.
      From a histopathologic perspective, clinically severe forms did not show with
      exclusive fibrotic changes. Further, there was no histopathologic marker
      predicting the clinical course or possible recurrence of the disease after
      surgical treatment. Only the clinical pre-operative RHISI score correlated with
      the postoperative outcome, with a high pre-operative RHISI being a risk factor
      for recurrence. CONCLUSION: Histopathologic features do not correlate with the
      clinical expression of rhinophyma. An exclusively 'fibrotic' rhinophyma form does
      not appear to exist and could possibly be the result of sampling error based on
      small biopsies studied.

PMID- 25950713
TI  - Use of Recirculating Ventilation With Dust Filtration to Improve Wintertime Air
      Quality in a Swine Farrowing Room.
AB  - The performance of a recirculating ventilation system with dust filtration was
      evaluated to determine its effectiveness to improve the air quality in a swine
      farrowing room of a concentrated animal feeding operation (CAFO). Air was
      exhausted from the room (0.47 m(3) sec(-1); 1000 cfm), treated with a filtration
      unit (Shaker-Dust Collector), and returned to the farrowing room to reduce dust
      concentrations while retaining heat necessary for livestock health. The air
      quality in the room was assessed over a winter, during which time limited fresh
      air is traditionally brought into the building. Over the study period, dust
      concentrations ranged from 0.005-0.31 mg m(-3) (respirable) and 0.17-2.09 mg m(
      3) (inhalable). In-room dust concentrations were reduced (41% for respirable and
      33% for inhalable) with the system in operation, while gas concentrations
      (ammonia [NH3], hydrogen sulfide [H2S], carbon monoxide [CO], carbon dioxide
      [CO2]) were unchanged. The position of the exhaust and return air systems
      provided reasonably uniform contaminant distributions, although the respirable
      dust concentrations nearest one of the exhaust ducts was statistically higher
      than other locations in the room, with differences averaging only 0.05 mg m(-3).
      Throughout the study, CO2 concentrations consistently exceeded 1540 ppm (industry
      recommendations) and on eight of the 18 study days it exceeded 2500 ppm (50% of
      the ACGIH TLV), with significantly higher concentrations near a door to a
      temperature-controlled hallway that was typically often left open. Alternative
      heaters are recommended to reduce CO2 concentrations in the room. Contaminant
      concentrations were modeled using production and environmental factors, with NH3
      related to the number of sow in the room and outdoor temperatures and CO2 related
      to the number of piglets and outdoor temperatures. The recirculating ventilation
      system provided dust reduction without increasing concentrations of hazardous
      gases.

PMID- 25950715
TI  - Pituitary dysfunction after traumatic brain injury: a clinical and
      pathophysiological approach.
AB  - Traumatic brain injury (TBI) is a growing public health problem worldwide and is
      a leading cause of death and disability. The causes of TBI include motor vehicle
      accidents, which are the most common cause, falls, acts of violence, sports
      related head traumas, and war accidents including blast-related brain injuries.
      Recently, pituitary dysfunction has also been described in boxers and kickboxers.
      Neuroendocrine dysfunction due to TBI was described for the first time in 1918.
      Only case reports and small case series were reported until 2000, but since then
      pituitary function in TBI victims has been investigated in more detail. The
      frequency of hypopituitarism after TBI varies widely among different studies (15
      50% of the patients with TBI in most studies). The estimates of persistent
      hypopituitarism decrease to 12% if repeated testing is applied. GH is the most
      common hormone lost after TBI, followed by ACTH, gonadotropins (FSH and LH), and
      TSH. The underlying mechanisms responsible for pituitary dysfunction after TBI
      are not entirely clear; however, recent studies have shown that genetic
      predisposition and autoimmunity may have a role. Hypopituitarism after TBI may
      have a negative impact on the pace or degree of functional recovery and
      cognition. What is not clear is whether treatment of hypopituitarism has a
      beneficial effect on specific function. In this review, the current data related
      to anterior pituitary dysfunction after TBI in adult patients are updated, and
      guidelines for the diagnosis, follow-up strategies, and therapeutic approaches
      are reported. 

PMID- 25950716
TI  - Optimal search strategies on complex multi-linked networks.
AB  - In this paper we consider the problem of optimal search strategies on multi
      linked networks, i.e. graphs whose nodes are endowed with several independent
      sets of links. We focus preliminarily on agents randomly hopping along the links
      of a graph, with the additional possibility of performing non-local hops to
      randomly chosen nodes with a given probability. We show that an optimal
      combination of the two jump rules exists that maximises the efficiency of target
      search, the optimum reflecting the topology of the network. We then generalize
      our results to multi-linked networks with an arbitrary number of mutually
      interfering link sets. 

PMID- 25950714
TI  - DNA Damage Signaling Is Induced in the Absence of Epstein-Barr Virus (EBV) Lytic
      DNA Replication and in Response to Expression of ZEBRA.
AB  - Epstein Barr virus (EBV), like other oncogenic viruses, modulates the activity of
      cellular DNA damage responses (DDR) during its life cycle. Our aim was to
      characterize the role of early lytic proteins and viral lytic DNA replication in
      activation of DNA damage signaling during the EBV lytic cycle. Our data challenge
      the prevalent hypothesis that activation of DDR pathways during the EBV lytic
      cycle occurs solely in response to large amounts of exogenous double stranded DNA
      products generated during lytic viral DNA replication. In immunofluorescence or
      immunoblot assays, DDR activation markers, specifically phosphorylated ATM
      (pATM), H2AX (gammaH2AX), or 53BP1 (p53BP1), were induced in the presence or
      absence of viral DNA amplification or replication compartments during the EBV
      lytic cycle. In assays with an ATM inhibitor and DNA damaging reagents in Burkitt
      lymphoma cell lines, gammaH2AX induction was necessary for optimal expression of
      early EBV genes, but not sufficient for lytic reactivation. Studies in lytically
      reactivated EBV-positive cells in which early EBV proteins, BGLF4, BGLF5, or
      BALF2, were not expressed showed that these proteins were not necessary for DDR
      activation during the EBV lytic cycle. Expression of ZEBRA, a viral protein that
      is necessary for EBV entry into the lytic phase, induced pATM foci and gammaH2AX
      independent of other EBV gene products. ZEBRA mutants deficient in DNA binding,
      Z(R183E) and Z(S186E), did not induce foci of pATM. ZEBRA co-localized with
      HP1beta, a heterochromatin associated protein involved in DNA damage signaling.
      We propose a model of DDR activation during the EBV lytic cycle in which ZEBRA
      induces ATM kinase phosphorylation, in a DNA binding dependent manner, to
      modulate gene expression. ATM and H2AX phosphorylation induced prior to EBV
      replication may be critical for creating a microenvironment of viral and cellular
      gene expression that enables lytic cycle progression. 

PMID- 25950718
TI  - Crossing boundaries: the design of an interdisciplinary training program to
      improve care for the frail elderly.
AB  - The Technology Evaluation in the Elderly Network (TVN) was funded in July 2012
      under the Canadian Networks of Centres of Excellence program. This article
      highlights the development and preliminary evaluation of the TVN
      Interdisciplinary Training Program. This program is based on an experiential
      learning approach that crosses a multitude of disciplines including health
      sciences, law, social sciences, and ethical aspects of working with the frail
      elderly. Opportunities within the program include mentorship, interdisciplinary
      online collaborative projects, external placements, academic products, pre-grant
      submission, trainee-driven requirements, Network meetings, online
      modules/webinars, and most importantly active involvement with patients,
      families, and their support systems. The authors have 120 trainees from
      approximately 23 different disciplines including law, ethics, public policy,
      social work, and engineering engaged in the program. Based on our evaluation this
      program has been perceived as highly valuable by the participants and the
      community. 

PMID- 25950717
TI  - Red cell distribution width in relation to incidence of stroke and carotid
      atherosclerosis: a population-based cohort study.
AB  - BACKGROUND: Increased red cell distribution width (RDW) has been related to poor
      prognosis in patients with cardiovascular disease, and is a predictor of
      cardiovascular mortality in the general population. The purpose of the present
      study was to investigate if RDW is associated with increased incidence of stroke
      and its subtypes in individuals from the general population. METHODS: Red cell
      distribution width was measured in 26,879 participants (16,561 women and 10,318
      men aged 45-73 years) without history of coronary events or stroke, from the
      population-based Malmo Diet and Cancer Study. Incidences of total stroke and
      stroke subtypes over a mean follow-up of 15.2 years were calculated in relation
      to sex-specific quartiles of RDW. The presence of carotid plaque and intima-media
      thickness, as assessed by ultrasound, was studied in relation to RDW in a
      randomly selected subcohort (n = 5,309). RESULTS: Incidences of total stroke (n =
      1,869) and cerebral infarction (n = 1,544) were both increased in individuals
      with high RDW. Hazard ratios (HRs) in the highest compared to the lowest quartile
      were 1.31 for total stroke (95% confidence interval [CI]: 1.11-1.54, p for trend
      = 0.004) and 1.32 for cerebral infarction (95% CI: 1.10-1.58, p for trend =
      0.004) after adjustment for stroke risk factors and hematological parameters. The
      adjusted HR for intracerebral hemorrhage (n = 230) was 1.44 (95% CI: 0.90-2.30)
      and the HR for subarachnoid hemorrhage (n = 75) was 0.94 (95% CI: 0.43-2.07), in
      the highest compared to the lowest quartile of RDW. Red cell distribution width
      was positively associated with intima-media thickness of the common carotid
      artery (p for trend = 0.011). CONCLUSIONS: Red cell distribution width in the
      highest quartile was associated with increased incidence of total stroke and
      cerebral infarction. There was no significant association between RDW and
      incidence of intracerebral or subarachnoid hemorrhage.

PMID- 25950719
TI  - Derivation and characterization of human embryonic stem cells on human amnion
      epithelial cells.
AB  - Culture conditions that support the growth of undifferentiated human embryonic
      stem cells (hESCs) have already been established using primary human amnion
      epithelial cells (hAECs) as an alternative to traditional mitotically inactivated
      mouse embryonic fibroblasts (MEFs). In the present work, inner cell masses (ICM)
      were isolated from frozen embryos obtained as donations from couples undergoing
      in vitro fertilization (IVF) treatment and four new hESC lines were derived using
      hAECs as feeder cells. This feeder system was able to support continuous growth
      of what were, according to their domed shape and markers, undifferentiated naive
      like hESCs. Their pluripotent potential were also demonstrated by embryoid bodies
      developing to the expected three germ layers in vitro and the productions of
      teratoma in vivo. The cell lines retained their karyotypic integrity for over 35
      passages. Transmission electron microscopy (TEM) indicated that these newly
      derived hESCs consisted mostly of undifferentiated cells with large nuclei and
      scanty cytoplasm. The new hESCs cultured on hAECs showed distinct
      undifferentiated characteristics in comparison to hESCs of the same passage
      maintained on MEFs. This type of optimized culture system may provide a useful
      platform for establishing clinical-grade hESCs and assessing the undifferentiated
      potential of hESCs. 

PMID- 25950721
TI  - Correction: Adding Vitamin E-TPGS to the Formulation of Genexol-PM: Specially
      Mixed Micelles Improve Drug-Loading Ability and Cytotoxicity against Multidrug
      Resistant Tumors Significantly.

PMID- 25950720
TI  - Subclinical Hypothyroidism and Elevated Thyroglobulin in Infants with Chronic
      Excess Iodine Intake.
AB  - BACKGROUND: Acute iodine excess in newborns can cause hypothyroidism, but there
      are limited data on the effects of iodine excess on thyroid function in older
      infants. The aim of this study was to measure the effects of chronic excess
      iodine intake on thyroid function in 6-24-month-old infants. METHODS: In this
      cross-sectional study, infants (n=696) in eastern Nepal were studied. Spot urine
      samples, venous blood samples, and household salt samples were collected, and
      urinary iodine concentration (UIC), serum free thyroxine (fT4), thyrotropin
      (TSH), thyroglobulin (Tg), and titrated household salt iodine concentration (SIC)
      were measured. Daily iodine intake was calculated from UIC based on estimates of
      urine volume at this age. RESULTS: Median (25th-75th percentile) household SIC
      was 89 (70-149) ppm, while national legislation stipulates a fortification level
      of 50 ppm. Median UIC was 407 (312-491) MUg/L; 76% of infants had a UIC >300
      MUg/L, suggesting iodine excess. Calculated mean iodine intake in 12-24-month-old
      infants was 220 MUg/day, exceeding the recommended safe upper limit for iodine at
      this age (200 MUg/day). Among the infants, 15.8% had an elevated Tg, 7.4% had
      subclinical hypothyroidism, but <1% had overt hypothyroidism. UIC was not a
      significant predictor of thyroid function, thyroid hormones, or Tg. CONCLUSION:
      In 6-24-month-old infants exposed to excessive iodine intake, ~7% have
      subclinical hypothyroidism but <1% have overt hypothyroidism. These findings
      suggest the thyroid in late infancy is already able to adapt to high iodine
      intakes and, in most cases, maintain euthyroidism.

PMID- 25950722
TI  - Accounting for experimental noise reveals that mRNA levels, amplified by post
      transcriptional processes, largely determine steady-state protein levels in
      yeast.
AB  - Cells respond to their environment by modulating protein levels through mRNA
      transcription and post-transcriptional control. Modest observed correlations
      between global steady-state mRNA and protein measurements have been interpreted
      as evidence that mRNA levels determine roughly 40% of the variation in protein
      levels, indicating dominant post-transcriptional effects. However, the techniques
      underlying these conclusions, such as correlation and regression, yield biased
      results when data are noisy, missing systematically, and collinear---properties
      of mRNA and protein measurements---which motivated us to revisit this subject.
      Noise-robust analyses of 24 studies of budding yeast reveal that mRNA levels
      explain more than 85% of the variation in steady-state protein levels. Protein
      levels are not proportional to mRNA levels, but rise much more rapidly.
      Regulation of translation suffices to explain this nonlinear effect, revealing
      post-transcriptional amplification of, rather than competition with,
      transcriptional signals. These results substantially revise widely credited
      models of protein-level regulation, and introduce multiple noise-aware approaches
      essential for proper analysis of many biological phenomena. 

PMID- 25950723
TI  - Study Looking at End Expiratory Pressure for Altitude Illness Decrease (SLEEP
      AID).
AB  - Lipman, Grant S., Nicholas C. Kanaan, Caleb Phillips, Dave Pomeranz, Patrick
      Cain, Kristin Fontes, Becky Higbee, Carolyn Meyer, Michael Shaheen, Sean
      Wentworth, and Diane Walsh. Study Looking at End Expiratory Pressure for Altitude
      Illness Decrease (SLEEP-AID). High Alt Med Biol 16:154-161, 2015.--Acute mountain
      sickness (AMS) affects 25%-70% of the tens of millions of high altitude travelers
      annually, with hypoxia and nocturnal desaturations as major contributing factors.
      This is the first double blind randomized placebo controlled trial to assess
      expiratory positive airway pressure (EPAP) for AMS prevention and nocturnal
      hypoxic events. Healthy adult participants trekking in the Khumbu region of the
      Himalayas were randomized to a single-use EPAP nasal strip, or a visually
      identical sham device (placebo) prior to first night sleeping between 4371-4530 m
      (14,340-14,800 ft). The primary outcome was AMS incidence, measured by Lake
      Louise Questionnaire (LLQ), with secondary outcomes of AMS severity (by LLQ) and
      physiologic sleep indices measured by continuous sleep monitor. Intent-to-treat
      analysis included 219 participants with comparable demographic characteristics,
      of which 115 received EPAP and 104 placebo. There was no decrease in AMS with
      EPAP intervention (14% EPAP vs. 17% placebo; p=0.65; risk difference (-)3.15%,
      95% CI (-)12.85%-6.56%). While overall AMS severity was not different between
      groups, EPAP reported decreased incidence of headache (64% vs. 76%; p<0.05, OR
      0.51, 95% CI 0.27-0.95) and dizziness (81% vs. 98%; p<0.03, OR 0.29, 95% CI 0.09
      0.78). During sleep, EPAP resulted in significant improvements in average
      peripheral oxygenation (Spo(2)) (80% versus 78%; p<0.01, mean difference=2, 95%
      CI 0.58-3.63) and a reduced percentage of time below 80% Spo(2) (31% vs. 46%;
      p<0.03, median difference=16, 95% CI 2.22-28.18). This lightweight and
      inexpensive EPAP device did not prevent acute mountain sickness, but did reduce
      the subgroup incidence of headache and dizziness while improving average
      nighttime peripheral oxygenation.

PMID- 25950724
TI  - Layer-selective half-metallicity in bilayer graphene nanoribbons.
AB  - Half-metallicity recently predicted in the zigzag-edge graphene nanoribbons
      (ZGNRs) and the hydrogenated carbon nanotubes (CNTs) enables fully spin-polarized
      electric currents, providing a basis for carbon-based spintronics. In both carbon
      systems, the half-metallicity arises from the edge-localized electron states
      under an electric field, lowering the critical electric field Dc for the half
      metallicity being an issue in recent works on ZGNRs. A properly chosen direction
      of the electric field alone has been predicted to significantly reduce Dc in the
      hydrogenated CNTs, which in this work turned out to be the case in narrow bilayer
      ZGNRs (biZGNRs). Here, our simple model based on the electrostatic potential
      difference between the edges predicts that for wide biZGNRs of width greater than
      ~2.0 nm (10 zigzag carbon chains), only one layer of the biZGNRs becomes half
      metallic leaving the other layer insulating as confirmed by our density
      functional theory (DFT) calculations. The electric field-induced switching of the
      spin-polarized current path is believed to open a new route to graphene-based
      spintronics applications. 

PMID- 25950725
TI  - A Limited-Memory BFGS Algorithm Based on a Trust-Region Quadratic Model for Large
      Scale Nonlinear Equations.
AB  - In this paper, a trust-region algorithm is proposed for large-scale nonlinear
      equations, where the limited-memory BFGS (L-M-BFGS) update matrix is used in the
      trust-region subproblem to improve the effectiveness of the algorithm for large
      scale problems. The global convergence of the presented method is established
      under suitable conditions. The numerical results of the test problems show that
      the method is competitive with the norm method. 

PMID- 25950726
TI  - An Overlooked Cardiac Adverse Effect of Letrozol Therapy: Myocardial Infarction
      due to Coronary Thrombus Formation.

PMID- 25950727
TI  - Fatty lesions in and around the heart: a pictorial review.
AB  - A wide variety of fat-containing entities occur in and near the heart. These
      findings are often encountered by radiologists and may be incidental or the
      reason for the patient's clinical presentation. Cross-sectional imaging helps to
      characterize the extent of these lesions and to formulate a differential
      diagnosis, which varies by lesion location, imaging features and patient
      demographics. The purpose of this pictorial essay is to familiarize radiologists
      with these fat-containing lesions and to help avoid misdiagnosis and errors in
      management. This pictorial review will discuss the normal fatty structures in and
      around the heart. A range of common and uncommon fat-containing lesions will then
      be reviewed based upon lesion location. 

PMID- 25950728
TI  - Deficit in motor training-induced clustering, but not stabilization, of new
      dendritic spines in FMR1 knock-out mice.
AB  - Fragile X Syndrome is the most common inherited intellectual disability, and
      Fragile X Syndrome patients often exhibit motor and learning deficits. It was
      previously shown that the fmr1 knock-out mice, a common mouse model of Fragile X
      Syndrome, recapitulates this motor learning deficit and that the deficit is
      associated with altered plasticity of dendritic spines. Here, we investigated the
      motor learning-induced turnover, stabilization and clustering of dendritic spines
      in the fmr1 knock-out mouse using a single forelimb reaching task and in vivo
      multiphoton imaging. We report that fmr1 knock-out mice have deficits in motor
      learning-induced changes in dendritic spine turnover and new dendritic spine
      clustering, but not the motor learning-induced long-term stabilization of new
      dendritic spines. These results suggest that a failure to establish the proper
      synaptic connections in both number and location, but not the stabilization of
      the connections that are formed, contributes to the motor learning deficit seen
      in the fmr1 knock-out mouse. 

PMID- 25950729
TI  - Exploring human brain lateralization with molecular genetics and genomics.
AB  - Lateralizations of brain structure and motor behavior have been observed in
      humans as early as the first trimester of gestation, and are likely to arise from
      asymmetrical genetic-developmental programs, as in other animals. Studies of gene
      expression levels in postmortem tissue samples, comparing the left and right
      sides of the human cerebral cortex, have generally not revealed striking
      transcriptional differences between the hemispheres. This is likely due to
      lateralization of gene expression being subtle and quantitative. However, a
      recent re-analysis and meta-analysis of gene expression data from the adult
      superior temporal and auditory cortex found lateralization of transcription of
      genes involved in synaptic transmission and neuronal electrophysiology.
      Meanwhile, human subcortical mid- and hindbrain structures have not been well
      studied in relation to lateralization of gene activity, despite being potentially
      important developmental origins of asymmetry. Genetic polymorphisms with small
      effects on adult brain and behavioral asymmetries are beginning to be identified
      through studies of large datasets, but the core genetic mechanisms of lateralized
      human brain development remain unknown. Identifying subtly lateralized genetic
      networks in the brain will lead to a new understanding of how neuronal circuits
      on the left and right are differently fine-tuned to preferentially support
      particular cognitive and behavioral functions. 

PMID- 25950730
TI  - Effects of reduced summer precipitation on productivity and forage quality of
      floodplain meadows at the Elbe and the Rhine River.
AB  - BACKGROUND: Floodplain meadows along rivers are semi-natural habitats and depend
      on regular land use. When used non-intensively, they offer suitable habitats for
      many plant species including rare ones. Floodplains are hydrologically dynamic
      ecosystems with both periods of flooding and of dry conditions. In German
      floodplains, dry periods may increase due to reduced summer precipitation as
      projected by climate change scenarios. Against this background, the question
      arises, how the forage quantity and quality of these meadows might change in
      future. METHODS: We report results of two field trials that investigated effects
      of experimentally reduced summer precipitation on hay quantity and quality of
      floodplain meadows at the Rhine River (2011-2012) and at two Elbe tributaries
      (2009-2011). We measured annual yield, the amount of hay biomass, and contents of
      crude protein, crude fibre, energy, fructan, nitrogen, phosphorus, and potassium.
      RESULTS: The annual yield decreased under precipitation reduction at the Rhine
      River. This was due to reduced productivity in the second cut hay at the Rhine
      River in which, interestingly, the contents of nitrogen and crude protein
      increased. The first cut at the Rhine River was unaffected by the treatments. At
      the Elbe tributaries, the annual yield and the hay quantity and quality of both
      cuts were only marginally affected by the treatments. CONCLUSION: We conclude
      that the yield of floodplain meadows may become less reliable in future since the
      annual yield decreased under precipitation reduction at the Rhine River. However,
      the first and agriculturally more important cut was almost unaffected by the
      precipitation reduction, which is probably due to sufficient soil moisture from
      winter/spring. As long as future water levels of the rivers will not decrease
      during spring, at least the use of the hay from the first cut of floodplain
      meadows appears reliable under climate change.

PMID- 25950731
TI  - The magnetic structure of EuCu2Sb2.
AB  - Antiferromagnetic ordering of EuCu2Sb2 which forms in the tetragonal CaBe2Ge2
      type structure (space group P4/nmm #129) has been studied using neutron powder
      diffraction and (151)Eu Mossbauer spectroscopy. The room temperature (151)Eu
      isomer shift of -12.8(1) mm s(-1) shows the Eu to be divalent, while the (151)Eu
      hyperfine magnetic field (B(hf)) reaches 28.7(2) T at 2.1 K, indicating a full
      Eu(2+) magnetic moment. B(hf)(T) follows a smooth S = 7/2 Brillouin function and
      yields an ordering temperature of 5.1(1) K. Refinement of the neutron diffraction
      data reveals a collinear A-type antiferromagnetic arrangement with the Eu moments
      perpendicular to the tetragonal c-axis. The refined Eu magnetic moment at 0.4 K
      is 7.08(15) MU(B) which is the full free-ion moment expected for the Eu(2+) ion
      with S = 7/2 and a spectroscopic splitting factor of g = 2.

PMID- 25950732
TI  - Fourth nerve palsy plus contralateral Horner syndrome secondary to mesencephalic
      haemorrhage: an unusual crossed syndrome.

PMID- 25950733
TI  - Resilience vs. historical contingency in microbial responses to environmental
      change.
AB  - How soil processes such as carbon cycling will respond to future climate change
      depends on the responses of complex microbial communities, but most ecosystem
      models assume that microbial functional responses are resilient and can be
      predicted from simple parameters such as biomass and temperature. Here, we
      consider how historical contingencies might alter those responses because
      function depends on prior conditions or biota. Functional resilience can be
      driven by physiological, community or adaptive shifts; historical contingencies
      can result from the influence of historical environments or a combination of
      priority effects and biotic resistance. By modelling microbial population
      responses to environmental change, we demonstrate that historical environments
      can constrain soil function with the degree of constraint depending on the
      magnitude of change in the context of the prior environment. For example
      microbial assemblages from more constant environments were more sensitive to
      change leading to poorer functional acclimatisation compared to microbial
      assemblages from more fluctuating environments. Such historical contingencies can
      lead to deviations from expected functional responses to climate change as well
      as local variability in those responses. Our results form a set of interrelated
      hypotheses regarding soil microbial responses to climate change that warrant
      future empirical attention. 

PMID- 25950734
TI  - Returning pharmacogenetic secondary findings from genome sequencing: let's not
      put the cart before the horse.

PMID- 25950735
TI  - With great (participant) rights comes great (researcher) responsibility.

PMID- 25950736
TI  - Isopentenyl diphosphate isomerase, a cholesterol synthesizing enzyme, is
      localized in Lewy bodies.
AB  - Isopentenyl diphosphate isomerase (IDI) is a cytoplasmic enzyme involved in the
      biosynthesis of isoprenoids including cholesterols. IDI has two isoforms in
      humans: IDI1 and IDI2. Since lipids are known to be a component of Lewy bodies
      (LBs), we investigated the immunohistochemical localization of IDI1 and IDI2 in
      the brain of patients with LB disease and multiple system atrophy (MSA) and
      normal control subjects. In normal controls, the cytoplasm of neurons was weakly
      immunostained with anti-IDI1 and anti-IDI2 antibodies throughout the nervous
      system. In LB disease, brainstem-type LBs were strongly positive for IDI1 and
      IDI2, and cortical LBs were unstained or barely immunolabeled. Double
      immunofluorescence staining revealed co-localization of phosphorylated alpha
      synuclein with IDI1 or IDI2. Glial cytoplasmic inclusions in MSA were unstained.
      Previous studies have shown that levels of cholesterol metabolites are increased
      in the cerebral cortex of patients with LB disease, and that these metabolites
      accelerate alpha-synuclein aggregation. The present findings suggest that IDI1
      and IDI2 may be associated with the production of cholesterol metabolites in
      neurons, leading to alpha-synuclein aggregation during the process of LB
      formation.

PMID- 25950737
TI  - Predicting the continuum between corridors and barriers to animal movements using
      Step Selection Functions and Randomized Shortest Paths.
AB  - The loss, fragmentation and degradation of habitat everywhere on Earth prompts
      increasing attention to identifying landscape features that support animal
      movement (corridors) or impedes it (barriers). Most algorithms used to predict
      corridors assume that animals move through preferred habitat either optimally
      (e.g. least cost path) or as random walkers (e.g. current models), but neither
      extreme is realistic. We propose that corridors and barriers are two sides of the
      same coin and that animals experience landscapes as spatiotemporally dynamic
      corridor-barrier continua connecting (separating) functional areas where
      individuals fulfil specific ecological processes. Based on this conceptual
      framework, we propose a novel methodological approach that uses high-resolution
      individual-based movement data to predict corridor-barrier continua with
      increased realism. Our approach consists of two innovations. First, we use step
      selection functions (SSF) to predict friction maps quantifying corridor-barrier
      continua for tactical steps between consecutive locations. Secondly, we introduce
      to movement ecology the randomized shortest path algorithm (RSP) which operates
      on friction maps to predict the corridor-barrier continuum for strategic
      movements between functional areas. By modulating the parameter ?, which controls
      the trade-off between exploration and optimal exploitation of the environment,
      RSP bridges the gap between algorithms assuming optimal movements (when ?
      approaches infinity, RSP is equivalent to LCP) or random walk (when ? -> 0, RSP 
      > current models). Using this approach, we identify migration corridors for GPS
      monitored wild reindeer (Rangifer t. tarandus) in Norway. We demonstrate that
      reindeer movement is best predicted by an intermediate value of ?, indicative of
      a movement trade-off between optimization and exploration. Model calibration
      allows identification of a corridor-barrier continuum that closely fits empirical
      data and demonstrates that RSP outperforms models that assume either optimality
      or random walk. The proposed approach models the multiscale cognitive maps by
      which animals likely navigate real landscapes and generalizes the most common
      algorithms for identifying corridors. Because suboptimal, but non-random,
      movement strategies are likely widespread, our approach has the potential to
      predict more realistic corridor-barrier continua for a wide range of species. 

PMID- 25950738
TI  - Bifunctional Sensing Mechanism of SnO2-ZnO Composite Nanofibers for Drastically
      Enhancing the Sensing Behavior in H2 Gas.
AB  - SnO2-ZnO composite nanofibers fabricated using an electrospinning method
      exhibited exceptional hydrogen (H2) sensing behavior. The existence of tetragonal
      SnO2 and hexagonal ZnO nanograins was confirmed by an analysis of the crystalline
      phase of the composite nanofibers. A bifunctional sensing mechanism of the
      composite nanofibers was proposed in which the combined effects of SnO2-SnO2
      homointerfaces and ZnO-SnO2 heterointerfaces contributed to an improvement in the
      H2 sensing characteristics. The sensing process with respect to SnO2-ZnO
      heterojunctions is associated not only with the high barrier at the junctions,
      but also the semiconductor-to-metallic transition on the surface of the ZnO
      nanograins upon the introduction of H2 gas. 

PMID- 25950740
TI  - Virulence factors as predictive tools for drug resistance in Pseudomonas
      aeruginosa.

PMID- 25950739
TI  - A dynamical phyllotaxis model to determine floral organ number.
AB  - How organisms determine particular organ numbers is a fundamental key to the
      development of precise body structures; however, the developmental mechanisms
      underlying organ-number determination are unclear. In many eudicot plants, the
      primordia of sepals and petals (the floral organs) first arise sequentially at
      the edge of a circular, undifferentiated region called the floral meristem, and
      later transition into a concentric arrangement called a whorl, which includes
      four or five organs. The properties controlling the transition to whorls
      comprising particular numbers of organs is little explored. We propose a
      development-based model of floral organ-number determination, improving upon
      earlier models of plant phyllotaxis that assumed two developmental processes: the
      sequential initiation of primordia in the least crowded space around the meristem
      and the constant growth of the tip of the stem. By introducing mutual repulsion
      among primordia into the growth process, we numerically and analytically show
      that the whorled arrangement emerges spontaneously from the sequential initiation
      of primordia. Moreover, by allowing the strength of the inhibition exerted by
      each primordium to decrease as the primordium ages, we show that pentamerous
      whorls, in which the angular and radial positions of the primordia are consistent
      with those observed in sepal and petal primordia in Silene coeli-rosa,
      Caryophyllaceae, become the dominant arrangement. The organ number within the
      outmost whorl, corresponding to the sepals, takes a value of four or five in a
      much wider parameter space than that in which it takes a value of six or seven.
      These results suggest that mutual repulsion among primordia during growth and a
      temporal decrease in the strength of the inhibition during initiation are
      required for the development of the tetramerous and pentamerous whorls common in
      eudicots. 

PMID- 25950741
TI  - Cunea n. g. (Amoebozoa, Dactylopodida) with two cryptic species isolated from
      different areas of the ocean.
AB  - This paper describes a new genus, Cunea n. g., of marine naked amoebae with two
      cryptic species, Cunea profundata and Cunea thuwala, isolated from distant
      localities in the ocean and different depths (Brazilian abyssal plain, Western
      Atlantic Ocean, depth >5km and the Red Sea off the Saudi Arabian coast, depth ca.
      58.7m). Both species are very similar to each other in the set of light
      microscopic and ultrastructural characters and might be described as a single
      species, yet their genetic divergence based on 3 molecular markers (small-subunit
      ribosomal RNA, actin and cytochrome c oxidase subunit 1) corresponds to the level
      of variation typically observed between different morphospecies of Amoebozoa. In
      addition, the studied strains differ strongly in their temperature tolerance
      ranges, C. profundata isolated from the cold Atlantic deep-sea habitat being able
      to reproduce under lower temperatures than C. thuwala isolated from the warm Red
      Sea benthos. Molecular phylogenetic analysis based on SSU rRNA gene shows that
      the new genus robustly branches within the Dactylopodida, but forms an
      independent clade within this order that does not group with any of its known
      genera. 

PMID- 25950742
TI  - Internalization and Subcellular Trafficking of Poly-l-lysine Dendrimers Are
      Impacted by the Site of Fluorophore Conjugation.
AB  - Internalization and intracellular trafficking of dendrimer-drug conjugates play
      an important role in achieving successful drug delivery. In this study, we aimed
      to elucidate the endocytosis mechanisms and subcellular localization of poly-l
      lysine (PLL) dendrimers in Caco-2 cells. We also investigated the impact of
      fluorophore conjugation on cytotoxicity, uptake, and transepithelial transport.
      Oregon green 514 (OG) was conjugated to PLL G3 at either the dendrimer periphery
      or the core. Chemical inhibitors of clathrin-, caveolin-, cholesterol-, and
      dynamin-mediated endocytosis pathways and macropinocytosis were employed to
      establish internalization mechanisms, while colocalization with subcellular
      markers was used to determine dendrimer trafficking. Cell viability,
      internalization, and uptake were all influenced by the site of fluorophore
      conjugation. Uptake was found to be highly dependent on cholesterol- and dynamin
      mediated endocytosis as well as macropinocytosis. Dendrimers were trafficked to
      endosomes and lysosomes, and subcellular localization was impacted by the
      fluorophore conjugation site. The results of this study indicate that PLL
      dendrimers exploit multiple pathways for cellular entry, and internalization and
      trafficking can be impacted by conjugation. Therefore, design of dendrimer-drug
      conjugates requires careful consideration to achieve successful drug delivery. 

PMID- 25950743
TI  - Genome-Wide Association Study of HIV-Related Lipoatrophy in Thai Patients:
      Association of a DLGAP1 Polymorphism with Fat Loss.
AB  - HIV-related lipoatrophy (LA) is a major adverse drug effect among HIV patients
      receiving the antiretroviral drug stavudine (d4T) in Southeast Asia. Although the
      development of LA could be observed in almost all HIV patients administered d4T
      for extended periods, there is considerable variation in the duration required to
      develop LA within this patient population. This study aimed to identify host
      genetic polymorphisms affecting the rate of LA onset in Thai HIV patients. We
      performed a genome-wide association study of HIV-related LA among patients at the
      Bamrasnaradura Infectious Diseases Institute, Thailand. Genotypes of HIV patients
      who developed LA within 2 years of treatment were compared with those of patients
      who did not develop LA after at least 4 years of treatment (non-LA patients).
      Genotypes of 49 LA and 92 non-LA patients at 578,525 single nucleotide
      polymorphisms (SNPs) were determined by Illumina bead arrays. The TaqMan real
      time PCR method was used in a replication study. Five SNPs in the bead arrays,
      which showed the lowest p values in a comparison of LA with non-LA patients, were
      further tested in independent and sex-matched subpopulations consisting of 95 LA
      and 95 non-LA patients. This replication study revealed a significant association
      of LA with an SNP (rs12964965) in the gene encoding the Disks Large Homolog
      Associated Protein 1 (DLGAP1), even after the correction for five multiple
      comparisons. These results strongly suggested involvement of the DLGAP1 gene
      product in the development of LA in Thai HIV patients. 

PMID- 25950744
TI  - SAXS data based global shape analysis of trigger factor (TF) proteins from E.
      coli, V. cholerae, and P. frigidicola: resolving the debate on the nature of
      monomeric and dimeric forms.
AB  - Dimerization of bacterial chaperone trigger factor (TF) is an inherent protein
      concentration based property which available biophysical characterization and
      crystal structures have kept debatable. We acquired small-angle X-ray scattering
      (SAXS) intensity data from different TF homologues from Escherichia coli (ECTF),
      Vibrio cholerae (VCTF), and Psychrobacter frigidicola (PFTF) while varying each
      protein concentration. We found that ECTF and VCTF adopt a compact dimeric shape
      at higher concentrations which did not resemble the "back-to-back" conformation
      reported earlier for ECTF from crystallography (PDB ID: 1W26 ). In contrast, PFTF
      remained monomeric throughout the concentration range 2-90 MUM displaying a
      multimodal open extended conformation. OLIGOMER analysis showed that both the
      ECTF and VCTF remained completely monomeric at lower concentrations (2-11 MUM),
      while, at higher concentrations (60-90 MUM), they adopted a dimeric form.
      Interestingly, the equilibrium existed in the medium concentration range (>11 and
      <60 MUM), which correlates with the physiological concentration (40-50 MUM) of TF
      in cell cytoplasm. Additionally, circular dichroism data revealed that solution
      structures of ECTF and VCTF contain predominantly alpha-helical content, while
      PFTF contains 310-helical content. 

PMID- 25950745
TI  - ZEB1 expression is correlated with tumor metastasis and reduced prognosis of
      breast carcinoma in Asian patients.
AB  - Tumor metastasis is one of the key events leading to tumor relapse and poor
      prognosis. Nowadays, increasing evidences demonstrated that ZEB1 was implicated
      in human carcinogenesis. However, involvement of ZEB1 deregulation in
      tumorigenesis in Asian patients with breast carcinoma remains elusive. The
      present study included 102 Asian patients with breast carcinoma treated by
      surgery from January of 2005 to December of 2006, and the expression of ZEB1 was
      evaluated by immunohistochemistry. To further assess the prognostic value of
      ZEB1, Kaplan-Meier curves were constructed. In this study, elevated levels of
      ZEB1 expression was found in carcinomas with higher aggressive potential. We also
      correlated expression of ZEB1 with lymph node metastasis (P = 0.021), advanced
      clinical stage (P = 0.012) in all cases, and high tumor grade (P = 0.047) in
      invasive ductal carcinoma. Furthermore, our data suggested an elevated level of
      Ki-67 expression in cases with positive expression of ZEB1. Clinically, reduced
      overall survival and disease-free survival were observed in cases with positive
      ZEB1 expression than that in negative cases. Our results correlated ZEB1 with
      aggressive potentials of breast carcinoma and revealed a possibility for ZEB1 as
      a prognostic marker in breast carcinoma. 

PMID- 25950746
TI  - Hot-Carrier Seebeck Effect: Diffusion and Remote Detection of Hot Carriers in
      Graphene.
AB  - We investigate hot carrier propagation across graphene using an electrical
      nonlocal injection/detection method. The device consists of a monolayer graphene
      flake contacted by multiple metal leads. Using two remote leads for electrical
      heating, we generate a carrier temperature gradient that results in a measurable
      thermoelectric voltage V(NL) across the remaining (detector) leads. Due to the
      nonlocal character of the measurement, V(NL) is exclusively due to the Seebeck
      effect. Remarkably, a departure from the ordinary relationship between Joule
      power P and V(NL), V(NL) ~ P, becomes readily apparent at low temperatures,
      representing a fingerprint of hot-carrier dominated thermoelectricity. By
      studying V(NL) as a function of bias, we directly determine the carrier
      temperature and the characteristic cooling length for hot-carrier propagation,
      which are key parameters for a variety of new applications that rely on hot
      carrier transport.

PMID- 25950747
TI  - Variability in lateralised blood flow response to language is associated with
      language development in children aged 1-5 years.
AB  - The developmental trajectory of language lateralisation over the preschool years
      is unclear. We explored the relationship between lateralisation of cerebral blood
      flow velocity response to object naming and cognitive performance in children
      aged 1-5 years. Functional transcranial Doppler ultrasound was used to record
      blood flow velocity bilaterally from middle cerebral arteries during a naming
      task in 58 children (59% male). At group level, the Lateralisation Index (LI)
      revealed a greater relative increase in cerebral blood flow velocity within the
      left as compared to right middle cerebral artery. After controlling for maternal
      IQ, left-lateralised children displayed lower expressive language scores compared
      to right- and bi-lateralised children, and reduced variability in LI. Supporting
      this, greater variability in lateralised response, rather than mean response, was
      indicative of greater expressive language ability. Findings suggest that a
      delayed establishment of language specialisation is associated with better
      language ability in the preschool years.

PMID- 25950748
TI  - A comparison of fluctuations of Campylobacter and Escherichia coli concentrations
      on broiler chicken carcasses during processing in two slaughterhouses.
AB  - The causes of differences in Campylobacter and Escherichia coli concentrations on
      broiler chicken carcasses after chilling between slaughterhouses are not fully
      identified. Therefore, it is a challenge for slaughterhouses to comply with
      Process Hygiene Criteria for broiler meat. The aim of the study was to identify
      which processing steps contribute to increases or decreases in Campylobacter and
      E. coli concentrations within and between two slaughterhouses. Identifying the
      processing steps with variable performance could explain the differences in
      bacterial concentrations after chilling between slaughterhouses. Thermotolerant
      Campylobacter and E. coli concentrations on carcasses during broiler processing
      were measured during the summer period in 21 trials after bleeding, scalding,
      defeathering, evisceration and chilling. In two slaughterhouses with comparable
      Campylobacter and E. coli concentrations in the incoming batches (after
      bleeding), the mean log10 concentrations are found to be significantly different
      after chilling. Campylobacter concentrations decreased by 1.40 log10 in
      Slaughterhouse 1 and by 1.86 log10 in Slaughterhouse 2, whereas E. coli decreased
      by 2.19 log10 in Slaughterhouse 1 and by 2.84 log10 in Slaughterhouse 2. Higher
      concentrations of Campylobacter and E. coli on carcasses after chilling were
      observed in Slaughterhouse 1 in which an increase in concentrations was observed
      after evisceration. The effect of processing on Campylobacter and E. coli
      concentrations in Slaughterhouse 1 did not differ between batches. In
      Slaughterhouse 2, the effect of processing on the concentrations of both bacteria
      varied over batches. Changes in E. coli concentration levels during processing
      were similar to Campylobacter except for defeathering. E. coli concentration
      significantly decreased after defeathering in both slaughterhouses, whereas
      Campylobacter increased in Slaughterhouse 2 and in Slaughterhouse 1 no
      significant changes were observed. The patterns of increases and decreases in
      bacterial concentrations during processing are specific for each slaughterhouse.
      Inhomogeneous patterns potentially explain the differences in concentrations
      after chilling between slaughterhouses. Critical processing steps should be
      validated in each slaughterhouse by longitudinal studies and potentially based on
      E. coli. E. coli has a potential to be used as an indicator of processing
      hygiene, because the impact of most of the studied processing steps was similar
      as for Campylobacter.

PMID- 25950750
TI  - Occupational history of night shift work and Parkinson's disease in Denmark.
AB  - OBJECTIVES: We investigated whether working night shifts was associated with the
      risk of Parkinson's disease (PD). METHODS: Between January 2008 and December
      2010, we recruited 1808 patients with a confirmed diagnosis of idiopathic PD from
      Denmark and 1876 population controls matched by year of birth and gender.
      Information on lifelong occupational history, including information on night
      work, smoking, caffeine and alcohol consumption habits, and family history of PD
      was collected through structured telephone interviews. RESULTS: Overall, there
      was no association between a history of night shift work and PD [odds ratio (OR)
      for any type of night work (ie, either permanent or rotating night work) 1.01,
      95% confidence interval (95% CI) 0.86-1.21]. Compared with persons who never
      worked night shifts, risks of those with longer durations of night work did not
      appear to differ (OR <10 years=0.95, 95% CI 0.75-1.19, OR 10-19 years= 1.09, 95%
      CI 0.77-1.53, OR >=20 years=1.05, 95% CI 0.81-1.37, P for trend=0.23).
      Associations were similar among men and women. CONCLUSIONS: These data suggest
      that working night shifts is not associated with PD or that low tolerance for
      night shift work is an early marker of PD. Due to the novel and exploratory
      nature of these findings, confirmation is needed.

PMID- 25950751
TI  - Combined Experimental and Computational Study of Pyren-2,7-diyl-Bridged
      Diruthenium Complexes with Various Terminal Ligands.
AB  - Cyclometalated diruthenium complexes 1(PF6)2-5(PF6)2 bridged by 1,3,6,8
      tetra(pyrid-2-yl)-pyrene have been prepared, with the terminal ligand bis(N
      methylbenzimidazolyl)pyridine (1(PF6)2), 4'-di-(p-methoxyphenyl)amino-2,2':6',2"
      terpyridine (2(PF6)2), 4'-p-methoxyphenyl-2,2':6',2"-terpyridine (3(PF6)2),
      2,2':6',2"-terpyridine (4(PF6)2), and trimethyl-4,4',4"-tricarboxylate-2,2':6',2"
      terpyridine (5(PF6)2). The single-crystal X-ray structure of 4(PF6)2 is
      presented. These complexes show two stepwise anodic redox pairs, and the
      potentials progressively increase from 1(PF6)2 to 5(PF6)2. Complexes 1(PF6)2
      4(PF6)2 have comparable electrochemical potential splitting of 200-210 mV, while
      complex 5(PF6)2 has a splitting of 170 mV. Upon one-electron oxidation by
      chemical oxidation or electrolysis, the resulting mixed-valent complexes 1(3+)
      5(3+) display broad and intense absorptions between 1000 and 3000 nm. Complexes
      1(3+) and 2(3+) show the presence of a higher-energy shoulder band in addition to
      the main near-infrared absorption band. This shoulder band is less distinguished
      for 3(3+)-5(3+). Three-state theory has been used to explain this difference. The
      one-electron oxidized forms, 1(3+)-5(3+), exhibit rhombic EPR signals at 77 K
      with the isotropic g values in the range of 2.18-2.24. Density functional theory
      (DFT) and time-dependent DFT (TDDFT) computations have been performed on 1(2+)
      5(2+) to characterize their electronic structures and rationalize the absorption
      spectra in a wide energy range. DFT computations on 1(3+)-5(3+) show that both
      ruthenium ions and the bridging ligand have comparable spin densities. TDDFT
      computations on 1(3+) and 4(3+) have been performed to complement the
      experimental results. 

PMID- 25950752
TI  - Quality Assessment of Clinical Practice Guidelines for Respiratory Diseases in
      China: A Systematic Appraisal.
AB  - BACKGROUND: There has been a significant increase in the publication of clinical
      practice guidelines (CPGs) for respiratory diseases in China. However, little is
      known about the quality and potential impacts of these CPGs. Our objective was to
      critically evaluate the quality of Chinese CPGs for respiratory diseases that
      were published in peer-reviewed medical journals. METHODS: A systematic search of
      scientific literature published between 1979 and 2013 was undertaken to identify
      and select CPGs that were related to respiratory diseases. Four Chinese databases
      (the Chinese Biomedical Literature database [CBM], the China National Knowledge
      Infrastructure [CNKI], the VIP database, and the WANFANG database) were used. The
      quality of eligible guidelines was assessed independently by four reviewers using
      the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument.
      The overall agreement among reviewers was evaluated using an intraclass
      correlation coefficient. RESULTS: A total of 109 guidelines published in 27
      medical journals from 1979 to 2013 were evaluated. The overall agreement among
      reviewers was considered good (intraclass correlation coefficient, 0.838; 95% CI,
      0.812-0.862). The scores of the six AGREE domains were low: 57.3% for scope and
      purpose (range, 4.2%-80.5%), 23.8% for stakeholder involvement (range, 2.8%
      54.2%), 7.7% for rigor of development (range, 0%-27.1%), 59.8% for clarity and
      presentation (range, 22.2%-80.6%), 10.9% for applicability (range, 0%-22.9%), and
      0.6% for editorial independence (range, 0%-16.7%). Scores for all guidelines were
      below 60%, and only three guidelines (2.8%) were recommended for clinical
      practice with modifications. CONCLUSIONS: The quality of the guidelines was low,
      and stakeholder involvement, rigor of development, applicability, and editorial
      independence should be considered in the future development of CPGs for
      respiratory diseases in China.

PMID- 25950753
TI  - A Dark Pigmented Spot in the Nasopharynx.

PMID- 25950754
TI  - Protection and Delivery of Anthelmintic Protein Cry5B to Nematodes Using
      Mesoporous Silicon Particles.
AB  - The ability of nano- and microparticles of partially oxidized mesoporous silicon
      (pSi) to sequester, protect, and deliver the anthelmintic pore-forming protein
      Cry5B to nematodes is assessed in vitro and in vivo. Thermally oxidized pSi
      particles are stable under gastric conditions and show relatively low toxicity to
      nematodes. Fluorescence images of rhodamine-labeled pSi particles within the
      nematodes Caenorhabditis elegans and Ancylostoma ceylanicum show that ingestion
      is dependent on particle size: particles of a 0.4 +/- 0.2 MUm size are noticeably
      ingested by both species within 2 h of introduction in vitro, whereas 5 +/- 2 MUm
      particles are excluded from C. elegans but enter the pharynx region of A.
      ceylanicum after 24 h. The anthelmintic protein Cry5B, a pore-forming crystal
      (Cry) protein derived from Bacillus thuringiensis, is incorporated into the pSi
      particles by aqueous infiltration. Feeding of Cry5B-loaded pSi particles to C.
      elegans leads to significant intoxication of the nematode. Protein-loaded
      particles of size 0.4 MUm display the highest level of in vitro toxicity toward
      C. elegans on a drug-mass basis. The porous nanostructure protects Cry5B from
      hydrolytic and enzymatic (pepsin) degradation in simulated gastric fluid (pH 1.2)
      for time periods up to 2 h. In vivo experiments with hookworm-infected hamsters
      show no significant reduction in worm burden with the Cry5B-loaded particles,
      which is attributed to slow release of the protein from the particles and/or
      short residence time of the particles in the duodenum of the animal. 

PMID- 25950755
TI  - Elucidating mechanisms for mental disorders: from specific molecules to
      pathology.

PMID- 25950757
TI  - SWOT analysis of program design and implementation: a case study on the reduction
      of maternal mortality in Afghanistan.
AB  - This case study analyzes the design and implementation of the Basic Package of
      Health Services (BPHS) in Afghanistan by synthesizing the literature with a focus
      on maternal health services. The authors are a group of graduate students in the
      Brandeis University International Health Policy and Management Program and
      Sustainable International Development Program who used the experience in
      Afghanistan to analyze an example of successfully implementing policy; two of the
      authors are Afghan physicians with direct experience in implementing the BPHS.
      Data is drawn from a literature review, and a unique aspect of the case study is
      the application of the business-oriented SWOT analysis to the design and
      implementation of the program that successfully targeted lowering maternal
      mortality in Afghanistan. It provides a useful example of how SWOT analysis can
      be used to consider the reasons for, or likelihood of, successful or unsuccessful
      design and implementation of a policy or program. Copyright (c) 2015 John Wiley &
      Sons, Ltd. 

PMID- 25950756
TI  - Purinergic signaling and energy homeostasis in psychiatric disorders.
AB  - Purinergic signaling regulates numerous vital biological processes in the central
      nervous system (CNS). The two principle purines, ATP and adenosine act as
      excitatory and inhibitory neurotransmitters, respectively. Compared to other
      classical neurotransmitters, the role of purinergic signaling in psychiatric
      disorders is not well understood or appreciated. Because ATP exerts its main
      effect on energy homeostasis, neuronal function of ATP has been underestimated.
      Similarly, adenosine is primarily appreciated as a precursor of nucleotide
      synthesis during active cell growth and division. However, recent findings
      suggest that purinergic signaling may explain how neuronal activity is associated
      neuronal energy charge and energy homeostasis, especially in mental disorders. In
      this review, we provide an overview of the synaptic function of mitochondria and
      purines in neuromodulation, synaptic plasticity, and neuron-glia interactions. We
      summarize how mitochondrial and purinergic dysfunction contribute to mental
      illnesses such as schizophrenia, bipolar disorder, autism spectrum disorder
      (ASD), depression, and addiction. Finally, we discuss future implications
      regarding the pharmacological targeting of mitochondrial and purinergic function
      for the treatment of psychiatric disorders. 

PMID- 25950759
TI  - High-rate volatile fatty acid (VFA) production by a granular sludge process at
      low pH.
AB  - Volatile fatty acids (VFA) are proposed platform molecules for the production of
      basic chemicals and polymers from organic waste streams. In this study we
      developed a granular sludge process to produce VFA at high rate, yield and purity
      while minimizing potential operational costs. A lab-scale anaerobic sequencing
      batch reactor (ASBR) was fed with 10 g l(-1) glucose as model substrate.
      Inclusion of a short (2 min) settling phase before effluent discharge enabled
      effective granulation and very high volumetric conversion rates of 150-300 gCOD
      l(-1)  d(-1) were observed during glucose conversion. The product spectrum
      remained similar at the tested pH range with acetate and butyrate as the main
      products, and a total VFA yield of 60-70% on chemical oxygen demand (COD) basis.
      The requirement for base addition for pH regulation could be reduced from 1.1 to
      0.6 mol OH(-) (mol glucose)(-1) by lowering the pH from 5.5 to 4.5. Solids
      concentrations in the effluent were 0.6 +/- 0.3 g l(-1) but could be reduced to
      0.02 +/- 0.01 g l(-1) by introduction of an additional settling period of 5 min.
      The efficient production of VFA at low pH with a virtually solid-free effluent
      increases the economic feasibility of waste-based chemicals and polymer
      production. Biotechnol.

PMID- 25950758
TI  - Parsing interindividual drug variability: an emerging role for systems
      pharmacology.
AB  - There is notable interindividual heterogeneity in drug response, affecting both
      drug efficacy and toxicity, resulting in patient harm and the inefficient
      utilization of limited healthcare resources. Pharmacogenomics is at the forefront
      of research to understand interindividual drug response variability, but although
      many genotype-drug response associations have been identified, translation of
      pharmacogenomic associations into clinical practice has been hampered by
      inconsistent findings and inadequate predictive values. These limitations are in
      part due to the complex interplay between drug-specific, human body and
      environmental factors influencing drug response and therefore pharmacogenomics,
      whilst intrinsically necessary, is by itself unlikely to adequately parse drug
      variability. The emergent, interdisciplinary and rapidly developing field of
      systems pharmacology, which incorporates but goes beyond pharmacogenomics, holds
      significant potential to further parse interindividual drug variability. Systems
      pharmacology broadly encompasses two distinct research efforts, pharmacologically
      orientated systems biology and pharmacometrics. Pharmacologically-orientated
      systems biology utilizes high throughput omics technologies, including next
      generation sequencing, transcriptomics and proteomics, to identify factors
      associated with differential drug response within the different levels of
      biological organization in the hierarchical human body. Increasingly complex
      pharmacometric models are being developed that quantitatively integrate factors
      associated with drug response. Although distinct, these research areas complement
      one another and continual development can be facilitated by iterating between
      dynamic experimental and computational findings. Ultimately, quantitative data
      derived models of sufficient detail will be required to help realize the goal of
      precision medicine.

PMID- 25950760
TI  - Ultrasound tissue characterization of vulnerable atherosclerotic plaque.
AB  - A thrombotic occlusion of the vessel fed by ruptured coronary atherosclerotic
      plaque may result in unstable angina, myocardial infarction or death, whereas
      embolization from a plaque in carotid arteries may result in transient ischemic
      attack or stroke. The atherosclerotic plaque prone to such clinical events is
      termed high-risk or vulnerable plaque, and its identification in humans before it
      becomes symptomatic has been elusive to date. Ultrasonic tissue characterization
      of the atherosclerotic plaque is possible with different techniques--such as
      vascular, transesophageal, and intravascular ultrasound--on a variety of arterial
      segments, including carotid, aorta, and coronary districts. The image analysis
      can be based on visual, video-densitometric or radiofrequency methods and
      identifies three distinct textural patterns: hypo-echoic (corresponding to lipid-
      and hemorrhage-rich plaque), iso- or moderately hyper-echoic (fibrotic or fibro
      fatty plaque), and markedly hyperechoic with shadowing (calcific plaque).
      Hypoechoic or dishomogeneous plaques, with spotty microcalcification and large
      plaque burden, with plaque neovascularization and surface irregularities by
      contrast-enhanced ultrasound, are more prone to clinical complications than
      hyperechoic, extensively calcified, homogeneous plaques with limited plaque
      burden, smooth luminal plaque surface and absence of neovascularization. Plaque
      ultrasound morphology is important, along with plaque geometry, in determining
      the atherosclerotic prognostic burden in the individual patient. New quantitative
      methods beyond backscatter (to include speed of sound, attenuation, strain,
      temperature, and high order statistics) are under development to evaluate
      vascular tissues. Although not yet ready for widespread clinical use, tissue
      characterization is listed by the American Society of Echocardiography roadmap to
      2020 as one of the most promising fields of application in cardiovascular
      ultrasound imaging, offering unique opportunities for the early detection and
      treatment of atherosclerotic disease.

PMID- 25950761
TI  - Evolutionary Analysis of the B56 Gene Family of PP2A Regulatory Subunits.
AB  - Protein phosphatase 2A (PP2A) is an abundant serine/threonine phosphatase that
      functions as a tumor suppressor in numerous cell-cell signaling pathways,
      including Wnt, myc, and ras. The B56 subunit of PP2A regulates its activity, and
      is encoded by five genes in humans. B56 proteins share a central core domain, but
      have divergent amino- and carboxy-termini, which are thought to provide isoform
      specificity. We performed phylogenetic analyses to better understand the
      evolution of the B56 gene family. We found that B56 was present as a single gene
      in eukaryotes prior to the divergence of animals, fungi, protists, and plants,
      and that B56 gene duplication prior to the divergence of protostomes and
      deuterostomes led to the origin of two B56 subfamilies, B56alphabetaepsilon and
      B56gammadelta. Further duplications led to three B56alphabetaepsilon genes and
      two B56gammadelta in vertebrates. Several nonvertebrate B56 gene names are based
      on distinct vertebrate isoform names, and would best be renamed. B56 subfamily
      genes lack significant divergence within primitive chordates, but each became
      distinct in complex vertebrates. Two vertebrate lineages have undergone B56 gene
      loss, Xenopus and Aves. In Xenopus, B56delta function may be compensated for by
      an alternatively spliced transcript, B56delta/gamma, encoding a B56delta-like
      amino-terminal region and a B56gamma core. 

PMID- 25950763
TI  - Design, Synthesis and Biological Evaluation of 1,4-Disubstituted-3,4
      dihydroisoquinoline Compounds as New Tubulin Polymerization Inhibitors.
AB  - A series of 1,4-disubstituted-3,4-dihydroisoquinoline derivatives designed as
      tubulin polymerization inhibitors were synthesized. Their cytotoxic activities
      against the CEM leukemia cell line were evaluated. Most of them displayed
      moderate cytotoxic activities, and compounds 21 and 32 showed good activities
      with IC50 of 4.10 and 0.64 MUM, respectively. The most potent compound 32 was
      further confirmed to be able to inhibit tubulin polymerization, and its
      hypothetical binding mode with tubulin was obtained by molecular docking. 

PMID- 25950762
TI  - The Heart Protection Effect of Alcalase Potato Protein Hydrolysate Is through
      IGF1R-PI3K-Akt Compensatory Reactivation in Aging Rats on High Fat Diets.
AB  - The prevalence of obesity is high in older adults. Alcalase potato protein
      hydrolysate (APPH), a nutraceutical food, might have greater benefits and be more
      economical than hypolipidemic drugs. In this study, serum lipid profiles and
      heart protective effects were evaluated in high fat diet (HFD) induced
      hyperlipidemia in aging rats treated with APPH (15, 45 and 75 mg/kg/day) and
      probucol (500 mg/kg/day). APPH treatments reduced serum triacylglycerol (TG),
      total cholesterol (TC), and low density lipoprotein (LDL) levels to the normal
      levels expressed in the control group. Additionally, the IGF1R-PI3K-Akt survival
      pathway was reactivated, and Fas-FADD (Fas-associated death domain) induced
      apoptosis was inhibited by APPH treatments (15 and 45 mg/kg/day) in HFD aging rat
      hearts. APPH (75 mg/kg/day) rather than probucol (500 mg/kg/day) treatment could
      reduce serum lipids without affecting HDL expression. The heart protective effect
      of APPH in aging rats with hyperlipidemia was through lowering serum lipids and
      enhancing the activation of the compensatory IGF1R-PI3K-Akt survival pathway. 

PMID- 25950764
TI  - Resistance of lung cancer cells grown as multicellular tumour spheroids to zinc
      sulfophthalocyanine photosensitization.
AB  - Photodynamic therapy (PDT) is phototherapeutic modality used in the treatment of
      neoplastic and non-neoplastic diseases. The photochemical interaction of light,
      photosensitizer (PS) and molecular oxygen produces singlet oxygen which induces
      cell death. Zinc sulfophthalocyanine (ZnPcSmix) has been shown to be effective in
      A549 monolayers, multicellular tumor spheroids (MCTSs) (250 um) and not on MCTSs
      with a size of 500 um. A549 cells used in this study were grown as MCTSs to a
      size of 500 um in order to determine their susceptibility to PDT. ZnPcSmix
      distribution in MCTSs and nuclear morphology was determined using a fluorescent
      microscope. Changes in cellular responses were evaluated using cell morphology,
      viability, proliferation, cytotoxicity, cell death analysis and mitochondrial
      membrane potential. Untreated MCTSs, showed no changes in cellular morphology,
      proliferation, cytotoxicity and nuclear morphology. Photoactivated ZnPcSmix also
      showed no changes in cellular morphology and nuclear morphology. However,
      photoactivated ZnPcSmix resulted in a significant dose dependant decrease in
      viability and proliferation as well as an increase in cell membrane damage in
      MCTSs over time. ZnPcSmix photosensitization induces apoptotic cell death in
      MCTSs with a size of 500 um and more resistantance when compared to monolayer
      cells and MCTSs with a size of 250 um. 

PMID- 25950765
TI  - Hierarchically ordered supramolecular protein-polymer composites with
      thermoresponsive properties.
AB  - Synthetic macromolecules that can bind and co-assemble with proteins are
      important for the future development of biohybrid materials. Active systems are
      further required to create materials that can respond and change their behavior
      in response to external stimuli. Here we report that stimuli-responsive linear
      branched diblock copolymers consisting of a cationic multivalent dendron with a
      linear thermoresponsive polymer tail at the focal point, can bind and complex
      Pyrococcus furiosus ferritin protein cages into crystalline arrays. The
      multivalent dendron structure utilizes cationic spermine units to bind
      electrostatically on the surface of the negatively charged ferritin cage and the
      in situ polymerized poly(di(ethylene glycol) methyl ether methacrylate) linear
      block enables control with temperature. Cloud point of the final product was
      determined with dynamic light scattering (DLS), and it was shown to be
      approximately 31  degrees C at a concentration of 150 mg/L. Complexation of the
      polymer binder and apoferritin was studied with DLS, small-angle X-ray
      scattering, and transmission electron microscopy, which showed the presence of
      crystalline arrays of ferritin cages with a face-centered cubic (fcc, Fm3m))
      Bravais lattice where lattice parameter a=18.6 nm. The complexation process was
      not temperature dependent but the final complexes had thermoresponsive
      characteristics with negative thermal expansion.

PMID- 25950766
TI  - Response of different genotypes of faba bean plant to drought stress.
AB  - Drought stress is one of the major abiotic stresses that are a threat to crop
      production worldwide. Drought stress impairs the plants growth and yield.
      Therefore, the aim of the present experiment was to select the tolerant
      genotype/s on the basis of moprpho-physiological and biochemical characteristics
      of 10 Vicia faba genotypes (Zafar 1, Zafar 2, Shebam, Makamora, Espan, Giza
      Blanka, Giza 3, C4, C5 and G853) under drought stress. We studied the effect of
      different levels of drought stress i.e., (i) normal irrigation (ii) mild stress
      (iii) moderate stress, and (iv) severe stress on plant height (PH) plant-1, fresh
      weight (FW) and dry weight (DW) plant-1, area leaf-1, leaf relative water content
      (RWC), proline (Pro) content, total chlorophyll (Total Chl) content, electrolyte
      leakage (EL), malondialdehyde (MDA), hydrogen peroxide (H2O2) content, and
      activities of catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD) of
      genotypes of faba bean. Drought stress reduced all growth parameters and Total
      Chl content of all genotypes. However, the deteriorating effect of drought stress
      on the growth performance of genotypes "C5" and "Zafar 1" were relatively low due
      to its better antioxidant enzymes activities (CAT, POD and SOD), and accumulation
      of Pro and Total Chl, and leaf RWC. In the study, genotype "C5" and "Zafar 1"
      were found to be relatively tolerant to drought stress and genotypes "G853" and
      "C4" were sensitive to drought stress. 

PMID- 25950767
TI  - In vitro biofilm development of Streptococcus pneumoniae and formation of choline
      binding protein-DNA complexes.
AB  - Extracellular deoxyribonucleic acid (eDNA) is an essential component of bacterial
      biofilm matrices, and is required in their formation and maintenance.
      Extracellular DNA binds to exopolysaccharides or extracellular proteins,
      affording biofilms greater structural integrity. Recently, we reported evidence
      of intercellular eDNA-LytC complexes in pneumococcal biofilms. The LytC lysozyme
      is a member of the choline-binding family of proteins (CBPs) located on the
      pneumococcal surface. The present work shows that other CBPs, i.e. LytA, LytB,
      Pce, PspC and CbpF, which have a pI between 5 and 6, can bind DNA in vitro. This
      process requires the presence of divalent cations other than Mg(2+). This DNA
      binding capacity of CBPs appears to be independent of their enzymatic activity
      and, at least in the case of LytA, does not require the choline-binding domain
      characteristic of CBPs. Positively charged, surface-exposed, 25 amino acid-long
      peptides derived from the catalytic domain of LytB, were also found capable of
      DNA binding through electrostatic interactions. Confocal laser scanning microcopy
      revealed the existence of cell-associated LytB-eDNA complexes in Streptococcus
      pneumoniae biofilms. These and other findings suggest that these surface-located
      proteins of S. pneumoniae could play roles of varying importance in the
      colonization and/or invasion of human host where different environmental
      conditions exist.

PMID- 25950768
TI  - Children Display Adult-Like Kinetic Patterns in the Time Domain, But Not in the
      Frequency Domain, While Walking With Ankle Load.
AB  - This study used both time and frequency domain analyses to investigate walking
      patterns with ankle load in children and adults. Twenty-two children aged 7-10
      years and 20 young adults participated in this study. Three levels of ankle load
      were manipulated: no load, low load (2% of body mass on each side), and high load
      (4% of body mass on each side). An instrumented treadmill was used to register
      vertical ground reaction force (GRF) and spatiotemporal parameters, and peak
      vertical GRFs were determined. A frequency domain analysis was conducted on the
      vertical GRF data. Results demonstrate that, in the time domain, children showed
      adult-like spatiotemporal parameters and adult-like timing and magnitude of the 2
      peak vertical GRFs under each load. In the frequency domain, children produced a
      lower power from the second harmonic than young adults, although both groups
      showed the highest power from this harmonic and increased this power with ankle
      load. It was concluded that children aged 7-10 years may start showing adult-like
      neuromuscular adaptations to increasing ankle load and display similar
      spatiotemporal control of foot falls and foot-floor kinetic interaction; however,
      a frequency domain analysis is effective in revealing different kinetic and
      neuromuscular characteristics between children and adults. 

PMID- 25950769
TI  - RACE RELATIONSHIPS: COLLEGIALITY AND DEMARCATION IN PHYSICAL ANTHROPOLOGY.
AB  - In 1962, anthropologist Carleton Coon argued in The Origin of Races that some
      human races had evolved further than others. Among his most vocal critics were
      geneticist Theodosius Dobzhansky and anthropologist Ashley Montagu, each of whom
      had known Coon for decades. I use this episode, and the long relationships
      between scientists that preceded it, to argue that scientific research on race
      was intertwined not only with political projects to conserve or reform race
      relations, but also with the relationships scientists shared as colleagues.
      Demarcation between science and pseudoscience, between legitimate research and
      scientific racism, involved emotional as well as intellectual labor. 

PMID- 25950770
TI  - Organocatalytic, Asymmetric Eliminative [4+2] Cycloaddition of Allylidene
      Malononitriles with Enals: Rapid Entry to Cyclohexadiene-Embedding Linear and
      Angular Polycycles.
AB  - A direct aminocatalytic synthesis has been developed for the chemo-, regio-,
      diastereo-, and enantioselective construction of densely substituted polycyclic
      carbaldehydes containing fused cyclohexadiene rings. The chemistry utilizes, for
      the first time, remotely enolizable pi-extended allylidenemalononitriles as
      electron-rich 1,3-diene precursors in a direct eliminative [4+2] cycloaddition
      with both aromatic and aliphatic alpha,beta-unsaturated aldehydes. The generality
      of the process is demonstrated by approaching 6,6-, 5,6-, 7,6-, 6,6,6-, and 6,5,6
      fused ring systems, as well as biorelevant steroid-like 6,6,6,6,5- and 6,6,6,5,6
      rings. A stepwise reaction mechanism for the key [4+2] addition is proposed as a
      domino bis-vinylogous Michael/Michael/retro-Michael reaction cascade. The utility
      of the malononitrile moiety as traceless activating group of the dicyano
      nucleophilic substrates is demonstrated. 

PMID- 25950771
TI  - Chains, necklaces and weaving chain-link grids from self-assembly reactions.
AB  - Assembly of two ditopic units, a phenanthroline substituted by 4-ethynyl
      pyridines at the 2-and 9-positions and a dimetallic paddlewheel, gives a linear
      chain polymer rather than a closed cyclic species, which would appear equally
      possible. The chain may be decorated by binding a copper-containing macrocycle
      around the phenanthroline units to form a polypseudorotaxane. When two
      phenanthroline ligands are assembled in a first step around copper(I), the
      paddlewheel acceptor can link them in a second step to form a two-dimensional
      interwoven grid that resembles the form of a chain-link fence. Each copper(I)
      centre in this structure is chiral, and the crystal shows complete homochirality,
      implying selection during the assembly process. 

PMID- 25950772
TI  - Inhibition of Ras signaling by blocking Ras-effector interactions with cyclic
      peptides.
AB  - Ras genes are frequently activated in human cancers, but the mutant Ras proteins
      remain largely "undruggable" through the conventional small-molecule approach
      owing to the absence of any obvious binding pockets on their surfaces. By
      screening a combinatorial peptide library, followed by structure-activity
      relationship (SAR) analysis, we discovered a family of cyclic peptides possessing
      both Ras-binding and cell-penetrating properties. These cell-permeable cyclic
      peptides inhibit Ras signaling by binding to Ras-GTP and blocking its interaction
      with downstream proteins and they induce apoptosis of cancer cells. Our results
      demonstrate the feasibility of developing cyclic peptides for the inhibition of
      intracellular protein-protein interactions and of direct Ras inhibitors as a
      novel class of anticancer agents. 

PMID- 25950773
TI  - Randomized Control Trial of the 3Rs Health Knowledge Training Program for Persons
      with Intellectual Disabilities.
AB  - BACKGROUND: Persons with intellectual disabilities (ID) experience a wide range
      of health problems. Research is needed on teaching persons with intellectual
      disabilities about their health to promote self-advocacy. This study used a RCT
      to evaluate a health knowledge training program for adults with intellectual
      disabilities and verbal skills. METHODS: Participants were randomly assigned to
      training (n = 12) or no training control (n = 10) groups. Topics included key
      body organs, systems, functions, health maintenance and illnesses. Participants
      played a game answering questions (e.g. 'What does the heart do?'). Instruction
      involved visuals (e.g., PowerPoint slides), cueing, modelling and feedback. The
      control group received pre-, post- and follow-up tests as the training group.
      RESULTS: The training group had significantly higher overall post-test and follow
      up health knowledge test scores than the control group. CONCLUSIONS: Health
      knowledge training is one step in promoting health self-advocacy and better
      health in persons with intellectual disabilities.

PMID- 25950775
TI  - The management of cervical mucus in obtaining a papanicolaou smear.
AB  - BACKGROUND: Our objective was to determine whether wiping of the cervix before
      taking a Papanicolaou smear aided cytological interpretation. MATERIALS AND
      METHODS: Three hundred nine women were randomly assigned to one of two groups. In
      one group, the subjects' cervixes were wiped before Papanicolaou smears were
      obtained. Smears were taken by uniformly trained practitioners and were read by
      cytologists in a blind fashion. RESULTS: There were no demographical differences
      between groups, nor were there differences between groups as to the quality of
      the smears or the diagnoses made. There were differences between groups as to
      remarks made by cytologists. The nonwiped group had thicker smears (p = .006) and
      more inflammation (p = .04). The wiped group showed more drying artifact (p =
      .001), crush artifact (p = .005), and limited cellular material (p = .007).
      CONCLUSIONS: It would appear that though there are no marked differences between
      the two techniques, wiping the cervix before obtaining the smear leads to less
      cellular material for comparison and predisposes to air drying. This technique
      may be less beneficial than was thought.

PMID- 25950774
TI  - CD44 and CXCL9 serum protein levels predict the risk of clinically significant
      allograft rejection after liver transplantation.
AB  - The diagnosis of acute cellular rejection (ACR) after liver transplantation is
      based on histological analysis of biopsies because noninvasive biomarkers for
      allograft rejection are not yet established for clinical routines. CD31, CD44,
      and chemokine (C-X-C motif) ligand (CXCL) 9 have previously been described as
      biomarkers for cross-organ allograft rejection. Here, we assessed the predictive
      and diagnostic value of these proteins as serum biomarkers for clinically
      significant ACR in the first 6 months after liver transplantation in a
      prospective study. The protein levels were measured in 94 patients immediately
      before transplantation, at postoperative days (PODs) 1, 3, 7, and 14 and when
      biopsies were performed during episodes of biochemical graft dysfunction. The
      CD44 serum protein levels were significantly lower at POD 1 in patients who
      experienced histologically proven ACR in the follow-up compared with patients
      without ACR (P < 0.001). CXCL9 was significantly higher before transplantation (P
      = 0.049) and at POD 1 (P < 0.001) in these patients. Low CD44 values (cutoff,
      <200.5 ng/mL) or high CXCL9 values (cutoff, >2.7 ng/mL) at POD 1 differentiated
      between rejection and no rejection with a sensitivity of 88% or 60% and a
      specificity of 61% or 79%, respectively. The combination of both biomarker
      cutoffs at POD 1 had a positive predictive value of 91% and a negative predictive
      value of 67% for clinically significant ACR. Moreover, CD44 was significantly
      lower at the time of ACR (P < 0.001) and differentiated the rejection group from
      patients with graft dysfunction due to other reasons. Our results suggest that
      CD44 and CXCL9 may serve as predictive biomarkers to identify liver allograft
      recipients at risk for clinically significant ACR.

PMID- 25950776
TI  - Evaluation of colposcopic skills in an obstetrics and gynecology residency
      training program.
AB  - OBJECTIVES: To evaluate objectively the colposcopic skills of resident physicians
      in an obstetrics and gynecology training program. METHODS: One hundred and ten
      colposcopic examinations were performed in a nonstructured fashion by 16 resident
      physicians supervised by the full-time gynecology faculty. Data were collected
      prospectively and were classified according to the resident's ability at
      colposcopic grading of cervical lesions (accuracy) and their ability to recognize
      the presence or absence of dysplasia (sensitivity and specificity, respectively)
      when compared to the corresponding histological interpretations. In addition,
      results between three groups were compared-junior residents (PGY1 and PGY2),
      senior residents (PGY3), and chief residents (PGY4)-to analyze learning
      progression. RESULTS: The numbers of evaluations performed by junior, senior, and
      chief residents were 43, 33, and 34, respectively. The overall accuracy,
      sensitivity, and specificity of the residents' colposcopic assessments were
      31.8%, 96.7%, and 22%, respectively. There was no difference in any of these
      measures between the groups analyzed. CONCLUSIONS: Residents correctly identified
      cervical dysplasia in the majority of cases but had difficulty in distinguishing
      between low-grade and high-grade cervical dysplasia and in differentiating
      dysplasia from benign cellular changes, such as metaplasia and inflammation.
      Colposcopic accuracy, sensitivity, and specificity did not seem to improve with
      increasing experience. Resident colposcopic skills may improve if more structured
      training is implemented, particularly if emphasis is placed on teaching
      differences between benign cellular changes and dysplastic lesions.

PMID- 25950777
TI  - Predictors of compliance with colposcopy referral in an indigent urban
      population.
AB  - BACKGROUND: The objective of this study was to determine whether
      sociodemographical and medical factors identify noncompliant patients referred
      for colposcopy. METHODS: Analysis factors determined by patient questionnaire and
      chart abstraction were analyzed by chi-square and Mann-Whitney tests. RESULTS: Of
      208 women referred, 159 were eligible for study and 27% (43 patients) were
      noncompliant. No factor distinguished compliant from initially noncompliant
      patients. To explain their noncompliance, women who initially failed to present
      for colposcopy cited transportation problems, lack of child care, and cost.
      CONCLUSIONS: Noncompliance with colposcopy among urban minority women is common,
      though barriers to compliance are multifactorial. However, sociodemographical and
      medical factors do not distinguish between complaint and initially noncompliant
      women presenting for colposcopy.

PMID- 25950778
TI  - Video colposcopy.
AB  - Video colposcopy is a new method for examining the lower genital tract. The video
      colposcopy system includes a video colposcope on a center pole or overhead boom,
      a high-resolution video monitor, and an optional image (data) management system.
      Because the video colposcope has no eyepieces, the technique differs from
      traditional colposcopy in that the colposcopist views the target only on the
      video monitor. A modified colposcopy technique is employed to assist depth
      perception, as the system does not permit stereoscopic viewing. The video
      colposcopy system, like other traditional optical colposcopes with attached video
      systems, enhances resident training and patient education. 

PMID- 25950779
TI  - ASCCP Practice Committee.

PMID- 25950781
TI  - Home study course: winter 1997.

PMID- 25950780
TI  - The plan for the journal of lower genital tract disease.

PMID- 25950782
TI  - The Triage of Women with ASCUS Cytology Using Human Papillomavirus DNA Testing.
AB  - OBJECTIVE: Our goal was to determine whether human papillomavirus (HPV) DNA
      testing is a valuable tool in triage of patients with cytology demonstrating
      atypical squamous cells of undetermined significance (ASCUS). METHODS: Our study
      included a total of 355 women who were referred for evaluation of a Papanicolaou
      smear with ASCUS diagnosed during routine screening. At the first visit, all
      patients had colposcopic examinations and HPV DNA testing by Hybrid Capture
      assay. Patients were evaluated every 4 to 6 months. Follow-up included repeat
      cytology and colposcopy at each visit; biopsy was performed if indicated.
      Followup continued for up to 2 years. RESULTS: Sensitivity, specificity, and
      positive and negative predictive values of HPV DNA testing in detecting cervical
      intraepithelial neoplasia grade 2 (CIN2) or CIN3 were 85%, 77%, 12%, and 99%,
      respectively. The prevalence of oncogenic HPV types was higher in patients
      younger than age 35 (35% versus 25%) in whom ASCUS-favor dysplasia/ASCUS-not
      otherwise specified was diagnosed. The presence of oncogenic HPV types equated
      with a 12.4% risk of biopsy-proven CIN2 and CIN3. The rate of CIN2 and CIN3 was
      0.4% in those who tested negative (95% confidence interval, 0-2.1%). CONCLUSIONS:
      HPV DNA testing appears to be a valuable tool for triage of women with ASCUS
      smears. Its high negative predictive value provides needed reassurance for follow
      up with only periodic cytology.

PMID- 25950783
TI  - Evaluating the HEDIS Guidelines for Measuring Cervical Cancer Prevention Efforts.
AB  - OBJECTIVE: Our goal was to evaluate the Health Plan Employer Data and Information
      Set (HEDIS) age criteria for measuring the quality of cervical cancer screening
      promulgated by the National Committee for Quality Assurance as a tool for
      assessing health plan performance. METHODS: Using a prospectively accrued
      database of women undergoing initial colposcopy at an urban teaching hospital
      between July 1, 1996, and December 31, 1997, we compared results of cytology,
      histology, and colposcopic impression for women within and outside the HEDIS age
      specifications for cervical cancer screening (ages 21-64 years). Histology was
      recorded as the highest-grade result from any cervical tissue obtained at or
      within 8 to 26 months after colposcopy. Women without cervices were excluded.
      Statistical analysis was by chisquare testing. RESULTS: As compared to 985 women
      meeting HEDIS age limits, 178 women aged 14 to 20 years had lower rates of
      histologically proven cervical intraepithelial neoplasia grade 2 (CIN2) or CIN3
      or cancer (288 of 985 [29%] versus 22 of 78 [28%]), as well as lower rates of
      high-grade cytology on referral and at the time of the colposcopy and lower-grade
      colposcopic impression (p < .001 for all). For 22 women older than age 64, rates
      of CIN2 or CIN3 or cancer on histology (6 of 22 [29%]), cytology, and colposcopic
      impression did not differ from those who were aged 20 to 64 (p > .15 for all).
      CONCLUSIONS: Adolescents referred for colposcopy are at lower risk for high-grade
      cervical disease than are women aged 21 to 64, but their 12% frequency of CIN2
      and CIN3 and cancer suggests that they deserve screening despite HEDIS
      recommendations.

PMID- 25950784
TI  - Hybrid Capture Human Papillomavirus Testing as an Adjunct to the Follow-Up of
      Patients with ASCUS and LGSIL Pap Smears: A Study of a Screening Population.
AB  - OBJECTIVES: We set out to evaluate Hybrid Capture (Digene Corporation, Silver
      Spring, MD) testing for human papillomavirus (HPV) in the management of a
      screening population with atypical squamous cells of undetermined significance
      (ASCUS) or low-grade squamous intraepithelial lesion (LGSIL). METHODS: A total of
      619 patients with ASCUS or LGSIL Papanicolaou smears were tested for high-risk
      HPV types. They then were followed at 6-month intervals with Papanicolaou smears
      and repeat HPV testing. Patients with persistent or progressive disease were
      referred for colposcopy. HPV results were compared to the most significant follow
      up cytological or colposcopic diagnosis to determine whether Hybrid Capture HPV
      testing was predictive of outcome. A cost analysis was performed. RESULTS: Follow
      up of 12 to 30 months was available for 471 patients (76.1%). Outcome diagnoses
      for 190 patients who initially tested HPV-positive were as follows: 49% benign,
      14% ASCUS, 19% LGSIL, 18% HGSIL, and 0.5% cancer. For 281 patients who initially
      tested HPV-negative, outcomes were 77% benign, 14% ASCUS, 6% LGSIL, 2% HGSIL, and
      0.3% cancer. Twenty-six of the patients with HGSIL had two or more HPV tests, and
      all these patients had at least one positive result. CONCLUSIONS: Hybrid Capture
      testing for high-risk HPV types was predictive of which patients presenting with
      ASCUS/LGSIL would persist or progress to HGSIL (p < .001). The cost of adding
      Hybrid Capture testing was intermediate between the cost of cytological follow-up
      and referral of all patients with ASCUS/LGSIL to colposcopy.

PMID- 25950785
TI  - Nodular hyperplasia of the bartholin gland increasing in size during sexual
      intercourse.
AB  - OBJECTIVE: A case of Bartholin gland nodular hyperplasia with review of the
      literature and diagnostic criteria is reported. MATERIAL AND METHODS: In a 31
      year-old woman, a nodular mass was found arising in the left labium minus. The
      mass size increased during sexual intercourse. RESULTS: The mass was well
      circumscribed but not encapsulated and showed a proliferation of acini lined by
      mucussecreting columnar epithelium. The lesion retained the lobular pattern and
      the relationship between acini and ducts as seen in the normal Bartholin gland.
      CONCLUSION: Nodular hyperplasia of the Bartholin gland should be differentiated
      from adenoma, in which architecture is disrupted. Variation in size during sexual
      intercourse probably is mediated by vascular engorgement. Surgical excision is
      curative.

PMID- 25950786
TI  - Nitrous oxide concentration during cryotherapy.
AB  - OBJECTIVE: The purpose of this study was to record room air concentrations of
      nitrous oxide during sessions of cryotherapy and to compare them with available
      norms. Complementary objectives were to determine the knowledge of Canadian
      colposcopists and to evaluate the need for education regarding nitrous oxide
      toxicities. MATERIAL AND METHODS: Air concentrations of nitrous oxide during
      cryotherapy sessions were measured with an infrared gas analyzer. A survey was
      sent to colposcopists throughout Canada to evaluate their knowledge of toxicities
      of nitrous oxide. RESULTS: The mean air concentrations of nitrous oxide measured
      were 169, 91, 99, and 103 ppm, respectively. Adding a tube to the cryotherapy
      scavenging outlet to dispose of the gas diminished the concentration to 17 ppm.
      The survey showed that 74% of the gynecologists surveyed use nitrous oxide as a
      refrigerant and only 18% know about the toxicities of nitrous oxide. CONCLUSION:
      Without a device to dispose of nitrous oxide securely during cryotherapy, the air
      concentration exceeds safe levels. Education of clinicians on the toxicities of
      nitrous oxide should be a goal in the future.

PMID- 25950787
TI  - Vulvar vestibulitis syndrome: a form of reflex sympathetic dystrophy?
AB  - OBJECTIVE: Our purpose was to determine whether vulvar vestibulitis syndrome is a
      form of reflex sympathetic dystrophy syndrome. MATERIALS AND METHODS: Between
      October 1, 1998, and February 16, 1999, 20 subjects attending a gynecology clinic
      at a tertiary care center received diagnoses of vulvar vestibulitis syndrome. A
      history was recorded, and a gynecological examination was performed for each,
      including a detailed description of the vulva, vaginal Gram's stain, vaginal
      culture, pH, and wet preparation of any discharge. Vulvar examination included
      assessing each subject's response to touch, pressure, pinprick, vibration, and
      cold. Subjects completed the short form of the McGill Pain Questionnaire.
      RESULTS: Twenty subjects with vulvar vestibulitis syndrome (average age, 30.6
      years; range, 20-71 years) had pain present an average of 4 years and 8 months
      (range, 6 months-33 years). Pain occurred with entry dyspareunia, tampon
      insertion, or touching of the vestibule. Vulvar vestibular erythema was present
      in 13 subjects. None of the 20 subjects felt pain to light touch on the vulvar
      vestibule. Light pressure produced allodynia in all 20. Nine subjects had
      hyperalgesia to pinprick; five subjects had allodynia in response to vibration;
      and three subjects experienced allodynia to cold. Summation and aftersensation to
      test modalities were uncommon. CONCLUSION: Though both vulvar vestibulitis and
      reflex sympathetic dystrophy seem to be neuropathic pain syndromes, they do not
      share enough physical characteristics to be considered the same pathological
      processes.

PMID- 25950788
TI  - A descriptive evaluation with follow-up of the clinical significance of atypical
      immature squamous metaplasia of the cervix.
AB  - OBJECTIVES: We set out to determine the clinical significance of atypical
      immature squamous metaplasia (AIM). METHODS: We performed in a military, hospital
      based colposcopy clinic a descriptive, retrospective review of patients who had a
      diagnosis of AIM. Patients were examined at 3- to 4-month intervals for at least
      1 year after a diagnosis of AIM was established. A gynecological pathologist
      reviewed all histological and cytological specimens. Initial histological or
      cytological specimens were tested for the presence of HPV DNA using in situ
      hybridization. RESULTS: High-risk HPV DNA types 16 or 18 were detected in 3% of
      patients with AIM. Concurrent cervical intraepithelial neoplasia 3 (CIN3) was
      noted in 3% of patients with AIM. One-third of patients with initially diagnosed
      AIM had complete resolution of this lesion after 1 year of follow-up.
      CONCLUSIONS: This descriptive, retrospective review shows that AIM does not
      appear to be associated with high-risk HPV DNA or with CIN3. In this limited
      study, a concurrent diagnosis of AIM likely does not influence the 1-year
      behavior of CIN. The degree of CIN should dictate treatment recommendations. A
      larger prospective trial is needed.

PMID- 25950790
TI  - Should a conization of the cervix have been performed prior to hysterectomy and
      bilateral salpingo-oophorectomy in this multiparous woman with cin3?

PMID- 25950789
TI  - Use of Psychosocial Effects of Abnormal Pap Smears Questionnaire (PEAPS-Q) in a
      Community Hospital Colposcopy Clinic.
AB  - OBJECTIVES: Our goal was to describe psychosocial distress using the Psychosocial
      Effects of Abnormal Pap Smears Questionnaire (PEAPS-Q), a 14-item, validated
      measure of anxiety and concern. MATERIALS AND METHODS: On presentation, a total
      of 142 subjects were given the PEAPS-Q and a demographic questionnaire (April
      1997-June 1998), both of which were completed prior to departure. Subjects were
      excluded for pregnancy, depression, or anxiety disorder. One hundred subjects
      remained for analysis using Epilnfo 6 (Centers for Disease Control and
      Prevention, Atlanta, GA). RESULTS: A PEAPS-Q score greater than 2.5 indicated the
      presence of psychosocial distress. Highest scores on the PEAPS-Q individual items
      were attributed to worry over developing cancer (57%; mean score, 3.18); to
      feeling tense during colposcopy (49%; mean score, 2.75); and to discomfort during
      the procedure (47%; mean score, 2.76). Seventy-three percent of subjects scored
      at least one item at 3 or greater. CONCLUSIONS: The PEAPS-Q revealed significant
      psychosocial distress focused on concern over developing cancer and on procedural
      discomfort. The data will be useful in providing focused patient education and
      counseling and in improving clinic practices.

PMID- 25950791
TI  - Four more years, four more years.

PMID- 25950792
TI  - Home study course: winter 2000.
AB  - ? OBJECTIVE: : The Home Study Course is intended for the practicing colposcopist
      or practitioner who is seeking to develop or enhance his or her colposcopic
      skills. The goal of the course is to present colposcopic cases that are unusual
      or instructive in terms of appearance, presentation, or management, or that
      demonstrate new and important knowledge in the area of colposcopy or pathology.
      Participants may benefit from reading and studying the material or from testing
      their knowledge by answering the questions. ? ACCME ACCREDITATION: : The American
      Society for Colposcopy and Cervical Pathology (ASCCP) is accredited by the
      Accreditation Council for Continuing Medical Education (ACCME) to sponsor
      continuing medical education for physicians. The ASCCP designates this continuing
      medical education activity for 1 credit hour in Category 1 of the Physician's
      Recognition Award of the American Medical Association. Credit is available for
      those who choose to apply. The Home Study Course is planned and produced in
      accordance with the ACCME's Essential Elements and Areas.

PMID- 25950794
TI  - Session schedule and registration form.

PMID- 25950793
TI  - The american society for colposcopy and cervical pathology hagerstown, MD.

PMID- 25950795
TI  - Impact of Healthcare Information Technology on Nursing Practice.
AB  - PURPOSE: To report additional mediation findings from a descriptive cross
      sectional study to examine if nurses' perceptions of the impact of healthcare
      information technology on their practice mediates the relationship between
      electronic nursing care reminder use and missed nursing care. DESIGN: The study
      used a descriptive design. The sample (N = 165) was composed of registered nurses
      working on acute care hospital units. The sample was obtained from a large
      teaching hospital in Southeast Michigan in the fall of 2012. All eligible nursing
      units (n = 19) were included. METHODS: The MISSCARE Survey, Nursing Care
      Reminders Usage Survey, and the Impact of Healthcare Information Technology Scale
      were used to collect data to test for mediation. Mediation was tested using the
      method described by Baron and Kenny. Multiple regression equations were used to
      analyze the data to determine if mediation occurred between the variables.
      FINDINGS: Missed nursing care, the outcome variable, was regressed on the
      predictor variable, reminder usage, and the mediator variable impact of
      technology on nursing practice. The impact of healthcare information technology
      (IHIT) on nursing practice negatively affected missed nursing care (t = -4.12, p
      < .001), explaining 9.8% of variance in missed nursing care. With IHIT present,
      the predictor (reminder usage) was no longer significant (t = -.70, p = .48).
      Thus, the reduced direct association between reminder usage and missed nursing
      care when IHIT was in the model supported the hypothesis that IHIT was at least
      one of the mediators in the relationship between reminder usage and missed
      nursing care. CONCLUSIONS: The perceptions of the impact of healthcare
      information technology mediates the relationship between nursing care reminder
      use and missed nursing care. The findings are beneficial to the advancement of
      healthcare technology in that designers of healthcare information technology
      systems need to keep in mind that perceptions regarding impacts of the technology
      will influence usage. CLINICAL RELEVANCE: Many times, information technology
      systems are not designed to match the workflow of nurses. Systems built with
      redundant or impertinent reminders may be ignored. System designers must study
      which reminders nurses find most useful and which reminders result in the best
      quality outcomes.

PMID- 25950796
TI  - Resilience to Social Bullying in Academia: A Phenomenological Study.
AB  - While social bullying, negative workplace behaviors, and incivility are receiving
      scholarly attention, no research study could be identified targeting resilience
      to social bullying in nursing programs. This article describes a phenomenological
      study that investigated resilience to social bullying. Seventeen self-identified
      bullied nurse faculty were audiotaped. Colaizzi's method guided data analysis.
      Multiple themes reflected 3 chronologic periods: during bullying, decisional
      phase, and after bullying. Implications for the health and well-being of nursing
      faculty are posed. 

PMID- 25950797
TI  - Implementation of Mock Competency Skill Assessments to Improve Student Outcomes.
AB  - A primary responsibility for nurse educators is to provide students with
      theoretical knowledge and clinical skills for professional nursing. In this
      study, laboratory faculty developed a creative pedagogical strategy to reduce
      nursing student stress during assessment of skill performance. Mock competencies
      were structured so that students participated in peer-to-peer evaluations in
      simulated competency assessments. The purpose of this study was to determine
      whether this pedagogical strategy had an impact on first-round pass rates for
      skills competency assessments. 

PMID- 25950798
TI  - "What Do I Do or Say?" Guiding Clinical Preceptors.

PMID- 25950800
TI  - Women, Work, and Illness: A Longitudinal Analysis of Workforce Participation
      Patterns for Women Beyond Middle Age.
AB  - BACKGROUND: Labor policies and economic incentives encourage women to work beyond
      middle age. However, women exhibit complex patterns of workforce participation
      over this life stage. This study examined transitions in and out of paid work
      across the life course of middle-aged women over a 14-year period and
      investigated associations between work and chronic diseases. METHODS: Latent
      class analysis identified dominant workforce participation patterns among 11,551
      middle-aged women from the 1946-1951 birth cohort of Australian Longitudinal
      Study on Women's Health. Multinomial logistic regression examined associations
      between work patterns and chronic diseases (diabetes, asthma, depression, and
      arthritis), while adjusting for health risk factors, sociodemographic factors and
      competing activities. RESULTS: Five latent classes were identified: "mostly in
      paid work" (48%), "early paid work" (9.4%), "increasingly paid work" (8.9%),
      "gradually not in paid work" (11.4%), and "mostly not in paid work" (22.3%).
      Results showed that women with chronic diseases (diabetes, asthma, depression,
      and arthritis) were less likely to be in paid work. These associations remained
      mostly unchanged after adjustments for other factors. CONCLUSIONS: The findings
      of this study provide better understanding of workforce participation patterns in
      women's late working life. This has important implications for policy design,
      aimed to engage middle-aged women in paid employment for longer in spite of
      chronic diseases and their complications. We suggest that there is a need for
      work place programs that support people with chronic diseases. Policies are also
      needed to facilitate better prevention and management of chronic health issues
      over the life course for women, in order to encourage workforce participation
      over later years.

PMID- 25950801
TI  - Association between shift work and severity of depressive symptoms among female
      nurses: the Korea Nurses' Health Study.
AB  - AIM: To determine the prevalence of depression and the relationship between shift
      work and depression severity among female nurses in South Korea. BACKGROUND:
      Shift work has been associated with higher risks of depressive symptoms, but
      there is a dearth of research on nurses, particularly investigating the severity
      of depressive symptoms. METHODS: Quantitative data including survey response from
      9789 participants were analysed. Statistical analysis included descriptive,
      Spearman's correlation and multivariable ordinal logistic regression. RESULTS:
      The numbers of nurses according to the severity of depressive symptoms were 35.2%
      (n = 3445), 38.0% (n = 3716), 16.1% (n = 1578), 7.6% (n = 747) and 3.1% (n = 303)
      for normal, mild, moderate, severely moderate and severe level of depressive
      symptoms, respectively. After adjusting for sociodemographic and health
      behavioural factors, nurses who worked shifts had 1.519-times greater odds of
      experiencing a higher severity of depressive symptoms (OR = 1.519, CI = 1.380
      1.674, P < 0.001). CONCLUSION: This study shows a higher prevalence of depressive
      symptoms among nurses who worked shifts and suggests that shift work may increase
      the severity of depressive symptoms among female nurses in South Korea.
      IMPLICATIONS FOR NURSING MANAGEMENT: Nursing professionals, managers and health
      policy makers need to understand the factors influencing depressive symptoms and
      to use appropriate interventions based on the severity and not just the onset.

PMID- 25950799
TI  - Analysis of Glioblastoma Patients' Plasma Revealed the Presence of MicroRNAs with
      a Prognostic Impact on Survival and Those of Viral Origin.
AB  - BACKGROUND: Glioblastoma multiforme (GBM) is among the most aggressive cancers
      with a poor prognosis in spite of a plethora of established diagnostic and
      prognostic biomarkers and treatment modalities. Therefore, the current goal is
      the detection of novel biomarkers, possibly detectable in the blood of GBM
      patients that may enable an early diagnosis and are potential therapeutic
      targets, leading to more efficient interventions. EXPERIMENTAL PROCEDURES:
      MicroRNA profiling of 734 human and human-associated viral miRNAs was performed
      on blood plasma samples from 16 healthy individuals and 16 patients with GBM,
      using the nCounter miRNA Expression Assay Kits. RESULTS: We identified 19 miRNAs
      with significantly different plasma levels in GBM patients, compared to the
      healthy individuals group with the difference limited by a factor of 2.
      Additionally, 11 viral miRNAs were found differentially expressed in plasma of
      GBM patients and 24 miRNA levels significantly correlated with the patients'
      survival. Moreover, the overlap between the group of candidate miRNAs for
      diagnostic biomarkers and the group of miRNAs associated with survival, consisted
      of ten miRNAs, showing both diagnostic and prognostic potential. Among them, hsa
      miR 592 and hsa miR 514a 3p have not been previously described in GBM and
      represent novel candidates for selective biomarkers. The possible signalling,
      induced by the revealed miRNAs is discussed, including those of viral origin, and
      in particular those related to the impaired immune response in the progression of
      GBM. CONCLUSION: The GBM burden is reflected in the alteration of the plasma
      miRNAs pattern, including viral miRNAs, representing the potential for future
      clinical application. Therefore proposed biomarker candidate miRNAs should be
      validated in a larger study of an independent cohort of patients.

PMID- 25950803
TI  - Association of a region of bovine chromosome 1 (BTA1) with age at puberty in
      Angus bulls.
AB  - Age at puberty is an important component of reproductive performance in cattle,
      so it is important to identify genes that contribute to the regulation of the
      onset of puberty and polymorphisms that explain differences between bulls. In a
      previous study, we found putative associations between age at puberty in Angus
      bulls and single-nucleotide polymorphisms (SNPs) in Chromosomes 1 and X. In the
      present work we aimed to confirm these findings in a larger sample of Angus bulls
      (n = 276). Four SNPs located in these regions were genotyped using SEQUENOM
      technology and the genotypes obtained were tested for association with age at
      puberty. The results showed that SNPs rs135953349 and rs110604205 on BTA1 were
      still significantly associated with age of puberty estimated at progressive sperm
      motility of 10% (P < 0.05). The association previously found on Chromosome X
      could not be confirmed. Analysis of the bovine genome revealed that the
      associated region (99.17-99.99 Mb) contained four predicted loci: myelodysplasia
      syndrome 1 (MDS1) and ecotropic virus integration site 1 (EVI1) complex locus
      (MECOM), eGF-like and EMI domain-containing 1 pseudogene-like (LOC100337483),
      microRNA mir-551b (MIR551B) and mCG140927-like (LOC100139843). The results
      obtained could contribute to the understanding of puberty regulation and could be
      useful for further identification and annotation of gene function in the context
      of reproduction.

PMID- 25950802
TI  - Netrin-1 - DCC Signaling Systems and Age-Related Macular Degeneration.
AB  - We conducted a nested candidate gene study and pathway-based enrichment analysis
      on data from a multi-national 77,000-person project on the molecular genetics of
      age-related macular degeneration (AMD) to identify AMD-associated DNA-sequence
      variants in genes encoding constituents of a netrin-1 (NTN1)-based signaling
      pathway that converges on DNA-binding transcription complexes through a 3'-5'
      cyclic adenosine monophosphate-calcineurin (cAMP-CN)-dependent axis. AMD
      associated single nucleotide polymorphisms (SNPs) existed in 9 linkage
      disequilibrium-independent genomic regions; these included loci overlapping NTN1
      (rs9899630, P <= 9.48 x 10(-5)), DCC (Deleted in Colorectal Cancer)--the gene
      encoding a primary NTN1 receptor (rs8097127, P <= 3.03 x 10(-5)), and 6 other
      netrin-related genes. Analysis of the NTN1-DCC pathway with exact methods
      demonstrated robust enrichment with AMD-associated SNPs (corrected P-value =
      0.038), supporting the idea that processes driven by NTN1-DCC signaling systems
      operate in advanced AMD. The NTN1-DCC pathway contains targets of FDA-approved
      drugs and may offer promise for guiding applied clinical research on preventive
      and therapeutic interventions for AMD.

PMID- 25950804
TI  - Identifying nurse practitioners' required case management competencies in health
      promotion practice in municipal public primary health care. A two-stage modified
      Delphi study.
AB  - AIMS AND OBJECTIVES: The aims of this study were to identify and reach consensus
      among municipal primary health care participants on nurse practitioners' (NPs')
      required case management competencies in health promotion practices in eastern
      Finland. BACKGROUND: The NP's role as a case manager of patients with chronic
      conditions has been found to have positive outcomes in health promotion, such as
      reduced hospital lengths of stay and readmission rates. However, the challenging
      work of health promotion requires NPs to have multidimensional competencies in
      health promotion, including communication, advocacy, assessment, planning,
      consultation and implementation. DESIGN: A two-stage modified Delphi study.
      METHODS: Round 1 semi-structured interviews were conducted among municipal
      primary health care participants (n = 42) in 11 health centres from April-July
      2009, and the round 2 questionnaire survey was conducted in the same health
      centres in eastern Finland in January and March 2011. The questionnaire was
      answered by 64% of those surveyed (n = 56). Content analysis and descriptive
      statistics were used for data analysis. RESULTS: We identified a total of 18
      required case management competencies for NPs' health promotion practices in
      municipal primary health care. In 17 of these competencies (such as knowledge,
      skills and ability to work independently in health promotion), a consensus was
      reached (51% or over). However, the need to be interested in municipal decision
      making (44.6%) did not reach consensus. CONCLUSION: Consensus was clearly
      achieved for 17 competencies that NPs were required to have, and these indicated
      the knowledge or abilities of health promotion. Nevertheless, there was no
      agreement on the NPs' need to be interested in municipal decision-making.
      RELEVANCE TO CLINICAL PRACTICE: NPs need a variety of case management skills and
      abilities to realise health promotion in municipal primary health care and they
      need to be supported by primary health care leaders to develop health promotion
      activities.

PMID- 25950805
TI  - Dermal eosinophilic infiltrate in junctional epidermolysis bullosa.
AB  - Junctional epidermolysis bullosa (JEB) is a rare genodermatosis characterized by
      a split in the lamina lucida usually because of mutations in LAMA3, LAMB3 and
      LAMC2 resulting in absence or reduction of laminin-332. Rare subtypes of JEB have
      mutations in COL17A1, ITGB4, ITGA6 and ITGA3 leading to reduction or dysfunction
      of collagen XVII, integrin alpha6beta4 and integrin alpha3. The classic finding
      under light microscopy is a paucicellular, subepidermal split. We describe the
      unusual presence of an eosinophilic infiltrate in the bullae and subjacent dermis
      in a neonate with JEB, generalized intermediate (formerly known as non-Herlitz
      type JEB), discuss the histologic differential diagnosis for a subepidermal
      blister in a neonate, review the literature regarding cases of epidermolysis
      bullosa (EB) presenting with inflammatory infiltrates, and discuss mechanisms to
      explain these findings. This case highlights that eosinophils can rarely be seen
      in EB and should not mislead the dermatopathologist into diagnosing an autoimmune
      blistering disorder. 

PMID- 25950806
TI  - Risks to health care workers from nano-enabled medical products.
AB  - Nanotechnology is rapidly expanding into the health care industry. However,
      occupational safety and health risks of nano-enabled medical products have not
      been thoroughly assessed. This manuscript highlights occupational risk mitigation
      practices for nano-enabled medical products throughout their life cycle for all
      major workplace settings including (1) medical research laboratories, (2)
      pharmaceutical manufacturing facilities, (3) clinical dispensing pharmacies, (4)
      health care delivery facilities, (5) home health care, (6) health care support,
      and (7) medical waste management. It further identifies critical research needs
      for ensuring worker protection in the health care industry. 

PMID- 25950807
TI  - Treatment of severe non-infectious uveitis in high-risk conditions (Part I):
      pregnancy and malignancies, management and safety issues.
AB  - INTRODUCTION: Management of patients with severe immune-mediated uveitis requires
      the use of immunosuppressive drugs in selected cases. This may be especially
      challenging in certain patients with concomitant conditions, which could increase
      the risk of side effects or modify guidelines for the use of such drugs.
      Therapeutic decision-making and management may be of particular difficulty in
      pregnancy as well as in patients with associated malignancies unrelated to a
      specific ophthalmic inflammatory condition. AREAS COVERED: The main aim of this
      review is to provide an updated comprehensive practical guide for practitioners
      regarding the therapeutic decision-making and management of patients with severe
      immune-mediated uveitis in the context of pregnancy and malignancies. EXPERT
      OPINION: Management of patients with immune-mediated uveitis requiring
      immunosuppressive/immunomodulatory drugs might be particularly complicated by
      other conditions affecting their health and immune status. Clinicians should take
      into account such conditions, which might influence treatment response and the
      clinical outcome of these patients.

PMID- 25950808
TI  - The Nucleoid Occlusion SlmA Protein Accelerates the Disassembly of the FtsZ
      Protein Polymers without Affecting Their GTPase Activity.
AB  - Division site selection is achieved in bacteria by different mechanisms, one of
      them being nucleoid occlusion, which prevents Z-ring assembly nearby the
      chromosome. Nucleoid occlusion in E. coli is mediated by SlmA, a sequence
      specific DNA binding protein that antagonizes FtsZ assembly. Here we show that,
      when bound to its specific target DNA sequences (SBS), SlmA reduces the lifetime
      of the FtsZ protofilaments in solution and of the FtsZ bundles when located
      inside permeable giant vesicles. This effect appears to be essentially uncoupled
      from the GTPase activity of the FtsZ protofilaments, which is insensitive to the
      presence of SlmA.SBS. The interaction of SlmA.SBS with either FtsZ protofilaments
      containing GTP or FtsZ oligomers containing GDP results in the disassembly of
      FtsZ polymers. We propose that SlmA.SBS complexes control the polymerization
      state of FtsZ by accelerating the disassembly of the FtsZ polymers leading to
      their fragmentation into shorter species that are still able to hydrolyze GTP at
      the same rate. SlmA defines therefore a new class of inhibitors of the FtsZ ring
      different from the SOS response regulator SulA and from the moonlighting enzyme
      OpgH, inhibitors of the GTPase activity. SlmA also shows differences compared
      with MinC, the inhibitor of the division site selection Min system, which
      shortens FtsZ protofilaments by interacting with the GDP form of FtsZ. 

PMID- 25950809
TI  - Decoupling the Lattice Distortion and Charge Doping Effects on the Phase
      Transition Behavior of VO2 by Titanium (Ti(4+)) Doping.
AB  - The mechanism for regulating the critical temperature (TC) of metal-insulator
      transition (MIT) in ions-doped VO2 systems is still a matter of debate, in
      particular, the unclear roles of lattice distortion and charge doping effects. To
      rule out the charge doping effect on the regulation of TC, we investigated Ti(4+)
      doped VO2 (Ti(x)V(1-x)O2) system. It was observed that the TC of Ti(x)V(1-x)O2
      samples first slightly decreased and then increased with increasing Ti
      concentration. X-ray absorption fine structure (XAFS) spectroscopy was used to
      explore the electronic states and local lattice structures around both Ti and V
      atoms in Ti(x)V(1-x)O2 samples. Our results revealed the local structure
      evolution from the initial anatase to the rutile-like structure around the Ti
      dopants. Furthermore, the host monoclinic VO2 lattice, specifically, the VO6
      octahedra would be subtly distorted by Ti doping. The distortion of VO6 octahedra
      and the variation of TC showed almost the similar trend, confirming the direct
      effect of local structural perturbations on the phase transition behavior. By
      comparing other ion-doping systems, we point out that the charge doping is more
      effective than the lattice distortion in modulating the MIT behavior of VO2
      materials.

PMID- 25950810
TI  - Abnormal Localization and Tumor Suppressor Function of Epithelial Tissue-Specific
      Transcription Factor ESE3 in Esophageal Squamous Cell Carcinoma.
AB  - Esophageal cancer is one of the most common malignant cancers worldwide. The
      molecular mechanism of esophageal squamous cell carcinoma (ESCC) is still poorly
      understood. ESE3 is a member of the Ets transcription family, which is only
      expressed in epithelial tissues and acts as a tumor suppressor gene in prostate
      cancer. Our study aim was to confirm whether ESE3 is involved in the
      carcinogenesis of ESCC. Immunohistochemical analysis revealed that ESE3 was
      mainly located in cell nuclei of normal tissues and the cytoplasm in ESCC
      tissues. Immunofluorescence and western blot analyses of the normal esophageal
      cell line HEEpiC and ESCC cell lines EC9706 TE-1, KYSE150, and KYSE410 confirmed
      these results. pEGFP-ESE3 and pcDNA3.1-V5/HisA-ESE3 plasmids were constructed for
      overexpression of ESE3 in EC9706 and KYSE150 cells. The stably transfected cells
      showed restoration of the nuclear localization of ESE3. EC9706 cells with re
      localization of ESE3 to the nucleus showed inhibition of proliferation, colony
      formation, migration, and invasion. To explore the possible mechanism of the
      differences in localization of ESE3 in normal esophageal cells and ESCC cells,
      ESCC cell lines were treated with the nuclear export inhibitor leptomycin B,
      transcription inhibitor actinomycin D, PKC inhibitor sphinganine, P38 MAPK
      inhibitor SB202190, and CK II inhibitor TBCA. These reagents were chosen
      according to the well-known mechanisms of protein translocation. However, the
      localization of ESE3 was unchanged after these treatments. The sequence of ESE3
      cDNA in ESCC cells was identical to the standard sequence of ESE3 in the NCBI
      Genebank database, indicating that there was no mutation in the coding region of
      ESE3 in ESCC. Taken together, our study suggests that ESE3 plays an important
      role in the carcinogenesis of ESCC through changes in subcellular localization
      and may act as a tumor suppressor gene in ESCC, although the mechanisms require
      further study. 

PMID- 25950811
TI  - Roles for education in development and implementation of evidence-based practices
      for community programs for older adults.
AB  - It is essential for key stakeholders in evidence-based practice (EBP) to be
      informed about barriers and achievements in EBP and collaborate in developing and
      implementing EBP. This article provides information to assist educators,
      students, practitioners, clients, and researchers who are stakeholders in use of
      EBP in community-based aging programs to understand barriers to EBP and
      approaches for developing and implementing EBP. Highlighting roles of education
      in EBP, the authors describe barriers to EBP; use of education to address gaps
      among research, education, and practice for EBP; cultural competence; and
      educational approaches for community-based implementation. EBP has been central
      to development of quality health and social services for older adults, but
      challenges remain in translation of research findings into EBP. Examples of
      programs in which research, education, and practice are linked for provision of
      EBP, as well as educational resources and tools for developing and implementing
      EBP, are identified. 

PMID- 25950812
TI  - Nonvolatile bio-memristor fabricated with egg albumen film.
AB  - This study demonstrates the fabrication and characterization of chicken egg
      albumen-based bio-memristors. By introducing egg albumen as an insulator to
      fabricate memristor devices comprising a metal/insulator/metal sandwich
      structure, significant bipolar resistive switching behavior can be observed. The
      1/f noise characteristics of the albumen devices were measured, and results
      suggested that their memory behavior results from the formation and rupture of
      conductive filaments. Oxygen diffusion and electrochemical redox reaction of
      metal ions under a sufficiently large electric field are the principal physical
      mechanisms of the formation and rupture of conductive filaments; these mechanisms
      were observed by analysis of the time-of-flight secondary ion mass spectrometry
      (TOF-SIMS) and resistance-temperature (R-T) measurement results. The switching
      property of the devices remarkably improved by heat-denaturation of proteins;
      reliable switching endurance of over 500 cycles accompanied by an on/off current
      ratio (Ion/off) of higher than 10(3) were also observed. Both resistance states
      could be maintained for a suitably long time (>10(4) s). Taking the results
      together, the present study reveals for the first time that chicken egg albumen
      is a promising material for nonvolatile memory applications. 

PMID- 25950813
TI  - RET Y791F Variant Does Not Increase the Risk for Medullary Thyroid Carcinoma.

PMID- 25950814
TI  - Men's Knowledge of Obstetric Danger Signs, Birth Preparedness and Complication
      Readiness in Rural Tanzania.
AB  - BACKGROUND: Men's involvement in reproductive health is recommended. Their
      involvement in antenatal care service is identified as important in maternal
      health. Awareness of obstetric danger signs facilitates men in making a joint
      decision with their partners regarding accessing antenatal and delivery care.
      This study aims to assess the level of knowledge of obstetric complications among
      men in a rural community in Tanzania, and to determine their involvement in birth
      preparedness and complication readiness. METHODS: A cross-sectional survey was
      conducted where 756 recent fathers were invited through a two-stage cluster
      sampling procedure. A structured questionnaire was used to collect socio
      demographic characteristics, knowledge of danger signs and steps taken on birth
      preparedness and complication readiness. Data were analyzed using bivariate and
      multivariable logistic regression to determine factors associated with being
      prepared, with statistically significant level at p<0.05. RESULTS: Among the
      invited men, 95.9% agreed to participate in the community survey. Fifty-three
      percent could mention at least one danger sign during pregnancy, 43.9% during
      delivery and 34.6% during the postpartum period. Regarding birth preparedness and
      complication readiness, 54.3% had bought birth kit, 47.2% saved money, 10.2%
      identified transport, 0.8% identified skilled attendant. In general, only 12% of
      men were prepared. Birth preparedness was associated with knowledge of danger
      signs during pregnancy (AOR = 1.4, 95% CI: 1.8-2.6). It was less likely for men
      living in the rural area to be prepared (AOR=0.6, 95% CI; 0.5-0.8). CONCLUSION:
      There was a low level of knowledge of obstetric danger signs among men in a rural
      district in Tanzania. A very small proportion of men had prepared for childbirth
      and complication readiness. There was no effect of knowledge of danger signs
      during childbirth and postpartum period on being prepared. Innovative strategies
      that increase awareness of danger signs as well as birth preparedness and
      complication readiness among men are required. Strengthening counseling during
      antenatal care services that involve men together with partners is recommended.

PMID- 25950815
TI  - Distance from a fishing community explains fish abundance in a no-take zone with
      weak compliance.
AB  - There are numerous examples of no-take marine reserves effectively conserving
      fish stocks within their boundaries. However, no-take reserves can be rendered
      ineffective and turned into 'paper parks' through poor compliance and weak
      enforcement of reserve regulations. Long-term monitoring is thus essential to
      assess the effectiveness of marine reserves in meeting conservation and
      management objectives. This study documents the present state of the 15-year old
      no-take zone (NTZ) of South El Ghargana within the Nabq Managed Resource
      Protected Area, South Sinai, Egyptian Red Sea. Previous studies credited willing
      compliance by the local fishing community for the increased abundances of
      targeted fish within the designated NTZ boundaries compared to adjacent fished or
      take-zones. We compared benthic habitat and fish abundance within the NTZ and the
      adjacent take sites open to fishing, but found no significant effect of the
      reserve. Instead, the strongest evidence was for a simple negative relationship
      between fishing pressure and distance from the closest fishing village. The
      abundance of targeted piscivorous fish increased significantly with increasing
      distance from the village, while herbivorous fish showed the opposite trend. This
      gradient was supported by a corresponding negative correlation between the amount
      of discarded fishing gear observed on the reef and increasing distance from the
      village. Discarded fishing gear within the NTZ suggested decreased compliance
      with the no-take regulations. Our findings indicate that due to non-compliance
      the no-take reserve is no longer functioning effectively, despite its apparent
      initial successes and instead a gradient of fishing pressure exists with distance
      from the nearest fishing community. 

PMID- 25950817
TI  - Repetitive Peripheral Magnetic Stimulation With Intensive Swallowing
      Rehabilitation for Poststroke Dysphagia: An Open-Label Case Series.
AB  - OBJECTIVE: The purpose of this pilot study was to determine the safety and
      feasibility of a six-day protocol of in-hospital repetitive peripheral magnetic
      stimulation combined with intensive swallowing rehabilitation (rPMS-ISR) for
      poststroke dysphagia. METHODS: The subjects were eight patients with dysphagia
      caused by bilateral cerebral infarction (age: 62-70; time from onset of stroke:
      27-39 months). rPMS was applied to the suprahyoid muscles, at strength set at 90%
      of the minimal intensity that elicited pain with a parabolic coil. One train of
      stimuli comprised 20 Hz for 3 sec followed by 27-sec rest. A single session
      included delivery of repetitive 20 trains of stimuli over 10 min, followed by 20
      min of swallowing rehabilitation. Each patient received this combination
      treatment twice daily, morning and afternoon, over six consecutive days.
      Swallowing function was evaluated before and after intervention. RESULTS: rPMS
      ISR induced significant improvement in swallowing ability, laryngeal elevation
      delay time, penetration aspiration scale, and swallowing quality of life (p <
      0.01), but had no significant effect on the functional oral intake scale.
      CONCLUSION: The six-day in-hospital RPMS-ISR protocol seems safe and feasible for
      poststroke patients with dysphagia. The combination protocol improved swallowing
      function. Further larger studies are needed to confirm its efficacy.

PMID- 25950816
TI  - Probing the Physicochemical Boundaries of Cell Permeability and Oral
      Bioavailability in Lipophilic Macrocycles Inspired by Natural Products.
AB  - Cyclic peptide natural products contain a variety of conserved, nonproteinogenic
      structural elements such as d-amino acids and amide N-methylation. In addition,
      many cyclic peptides incorporate gamma-amino acids and other elements derived
      from polyketide synthases. We hypothesized that the position and orientation of
      these extended backbone elements impact the ADME properties of these hybrid
      molecules, especially their ability to cross cell membranes and avoid metabolic
      degradation. Here we report the synthesis of cyclic hexapeptide diastereomers
      containing gamma-amino acids (e.g., statines) and systematically investigate
      their structure-permeability relationships. These compounds were much more water
      soluble and, in many cases, were both more membrane permeable and more stable to
      liver microsomes than a similar non-statine-containing derivative. Permeability
      correlated well with the extent of intramolecular hydrogen bonding observed in
      the solution structures determined in the low-dielectric solvent CDCl3, and one
      compound showed an oral bioavailability of 21% in rat. Thus, the incorporation of
      gamma-amino acids offers a route to increase backbone diversity and improve ADME
      properties in cyclic peptide scaffolds. 

PMID- 25950818
TI  - Effect of Phenylephrine Pretreatment on the Expressions of Aquaporin 5 and c-Jun
      N-Terminal Kinase in Irradiated Submandibular Gland.
AB  - Radiotherapy for malignant tumors of the head and neck commonly leads to
      radiation-induced sialadenitis as a result of radiation-induced salivary gland
      dysfunction. We demonstrated previously that phenylephrine could protect the
      irradiated submandibular gland against apoptosis, although the mechanism is
      unclear. In this study, we investigated the influence of phenylephrine
      pretreatment on the expressions of aquaporin 5 (AQP5) and c-Jun N-terminal kinase
      (JNK) that were presumed to have a role in radiation-induced salivary gland
      dysfunction. Rats pretreated with phenylephrine (5 mg/kg) were locally irradiated
      (20 Gy) in the head and neck region. The submandibular glands were removed on day
      7 after irradiation. The expression of AQP5 and activation of JNK were measured
      by immunohistochemistry and Western blot. The localization of AQP5 at the apical
      and lateral plasma membrane of acinar cells was significantly reduced by
      irradiation, but markedly enhanced with phenylephrine pretreatment. The protein
      expression of AQP5 was decreased by 84.91% in irradiated glands, whereas it was
      fully recovered to the control level in phenylephrine-pretreated glands.
      Moreover, many acinar, ductal and granular convoluted tubular cells in the
      irradiated glands exhibited intense immunoreactivity for p-JNK, while in the
      phenylephrine-pretreated irradiated glands, only a few acinar cells exhibited
      very faint immunoreactivity for p-JNK. The protein expression level of p-JNK was
      increased by 41.65% in the irradiated alone glands, but was significantly
      decreased in the phenylephrine-pretreated irradiated glands. These results
      suggest that the protective mechanism of phenylephrine might be related to the
      improved expression of AQP5 and decreased activation of JNK. Pretreatment with
      phenylephrine in patients undergoing radiotherapy may provide a helpful strategy
      for suppression of radiation-induced sialadenitis. 

PMID- 25950819
TI  - Investigation of DNA Damage Dose-Response Kinetics after Ionizing Radiation
      Schemes Similar to CT Protocols.
AB  - Although there has been extensive research done on the biological response to
      doses of ionizing radiation relevant to radiodiagnostic procedures, very few
      studies have examined radiation schemes similar to those frequently utilized in
      CT exams. Instead of a single exposure, CT exams are often made up of a series of
      scans separated on the order of minutes. DNA damage dose-response kinetics after
      radiation doses and schemes similar to CT protocols were established in both
      cultured (ESW-WT3) and whole blood lymphocytes and compared to higher dose
      exposures. Both the kinetics and extent of H2AX phosphorylation were found to be
      dose dependent. Damage induction and detection showed a clear dose response,
      albeit different, at all time points and differences in the DNA repair kinetics
      of ESW-WT3 and whole blood lymphocytes were characterized. Moreover, using a
      modified split-dose in vitro experiment, we show that phosphorylation of H2AX is
      significantly reduced after exposure to CT doses fractionated over a few minutes
      compared to the same total dose delivered as a single exposure. Because the split
      dose exposures investigated here are more similar to those experienced during a
      CT examination, it is essential to understand why and how these differences
      occur. This work provides compelling evidence supporting differential biological
      responses not only between high and low doses, but also between single and
      multiple exposures to low doses of ionizing radiation. 

PMID- 25950820
TI  - Mimicking high-silica zeolites: highly stable germanium- and tin-rich zeolite
      type chalcogenides.
AB  - High-silica zeolites, as exemplified by ZSM-5, with excellent chemical and
      thermal stability, have generated a revolution in industrial catalysis. In
      contrast, prior to this work, high-silica-zeolite-like chalcogenides based on
      germanium/tin remained unknown, even after decades of research. Here six
      crystalline high-germanium or high-tin zeolite-type sulfides and selenides with
      four different topologies are reported. Their unprecedented framework
      compositions give these materials much improved thermal and chemical stability
      with high surface area (Langmuir surface area of 782 m(2)/g(-1)) comparable to or
      better than zeolites. Among them, highly stable CPM-120-ZnGeS allows for ion
      exchange with diverse metal or complex cations, resulting in fine-tuning in
      porosity, fast ion conductivity, and photoelectric response. Being among the most
      porous crystalline chalcogenides, CPM-120-ZnGeS (exchanged with Cs(+) ions) also
      shows reversible adsorption with high capacity and affinity for CO2 (98 and 73
      cm(3) g(-1) at 273 and 298 K, respectively, isosteric heat of adsorption = 40.05
      kJ mol(-1)). Moreover, CPM-120-ZnGeS could also function as a robust
      photocatalyst for water reduction to generate H2. The overall activity of H2
      production from water, in the presence of Na2S-Na2SO3 as a hole scavenger, was
      200 MUmol h(-1)/(0.10 g). Such catalytic activity remained undiminished under
      illumination by UV light for as long as measured (200 h), demonstrating excellent
      resistance to photocorrosion even under intense UV radiation. 

PMID- 25950821
TI  - Blind Depth-variant Deconvolution of 3D Data in Wide-field Fluorescence
      Microscopy.
AB  - This paper proposes a new deconvolution method for 3D fluorescence wide-field
      microscopy. Most previous methods are insufficient in terms of restoring a 3D
      cell structure, since a point spread function (PSF) is simply assumed as depth
      invariant, whereas a PSF of microscopy changes significantly along the optical
      axis. A few methods that consider a depth-variant PSF have been proposed;
      however, they are impractical, since they are non-blind approaches that use a
      known PSF in a pre-measuring condition, whereas an imaging condition of a target
      image is different from that of the pre-measuring. To solve these problems, this
      paper proposes a blind approach to estimate depth-variant specimen-dependent PSF
      and restore 3D cell structure. It is shown by experiments on that the proposed
      method outperforms the previous ones in terms of suppressing axial blur. The
      proposed method is composed of the following three steps: First, a non-parametric
      averaged PSF is estimated by the Richardson Lucy algorithm, whose initial
      parameter is given by the central depth prediction from intensity analysis.
      Second, the estimated PSF is fitted to Gibson's parametric PSF model via
      optimization, and depth-variant PSFs are generated. Third, a 3D cell structure is
      restored by using a depth-variant version of a generalized expectation
      maximization. 

PMID- 25950822
TI  - Variation in patient position and impact on carbon-ion scanning beam distribution
      during prostate treatment.
AB  - OBJECTIVE: We assessed the impact of changes in patient position on carbon-ion
      scanning beam distribution during treatment for prostate cancer. METHODS: 68
      patients were selected. Carbon-ion scanning dose was calculated. Two different
      planning target volumes (PTVs) were defined: PTV1 was the clinical target volume
      plus a set-up margin for the anterior/lateral sides and posterior side, while
      PTV2 was the same as PTV1 minus the posterior side. Total prescribed doses of
      34.4 Gy [relative biological effectiveness (RBE)] and 17.2 Gy (RBE) were given to
      PTV1 and PTV2, respectively. To estimate the influence of geometric variations on
      dose distribution, the dose was recalculated on the rigidly shifted single
      planning CT based on two dimensional-three dimensional rigid registration of the
      orthogonal radiographs before and after treatment for the fraction of maximum
      positional changes. RESULTS: Intrafractional patient positional change values
      averaged over all patients throughout the treatment course were less than the
      target registration error = 2.00 mm and angular error = 1.27 degrees . However,
      these maximum positional errors did not occur in all 12 treatment fractions. Even
      though large positional changes occurred during irradiation in all treatment
      fractions, lowest dose encompassing 95% of the target (D95)-PTV1 was >98% of the
      prescribed dose. CONCLUSION: Intrafractional patient positional changes occurred
      during treatment beam irradiation and degraded carbon-ion beam dose distribution.
      Our evaluation did not consider non-rigid deformations, however, dose
      distribution was still within clinically acceptable levels. ADVANCES IN
      KNOWLEDGE: Inter- and intrafractional changes did not affect carbon-ion beam
      prostate treatment accuracy.

PMID- 25950823
TI  - Somatic V600E BRAF Mutation in Linear and Sporadic Syringocystadenoma
      Papilliferum.

PMID- 25950824
TI  - Th2 Cytokines Suppress Lipoteichoic Acid-Induced Matrix Metalloproteinase
      Expression and Keratinocyte Migration in Response to Wounding.

PMID- 25950825
TI  - Translational Repression Protects Human Keratinocytes from UVB-Induced Apoptosis
      through a Discordant eIF2 Kinase Stress Response.
AB  - This study delineates the mechanisms by which UVB regulates protein synthesis in
      human keratinocytes and the importance of translational control in cell survival.
      Translation initiation is regulated by phosphorylation of eukaryotic initiation
      factor 2 (eIF2-P) that causes decreased global protein synthesis coincident with
      enhanced translation of selected stress-related transcripts, such as activating
      transcription factor 4 (ATF4). ATF4 is a transcriptional activator of the
      integrated stress response (ISR) that has cytoprotective functions as well as
      apoptotic signals through the downstream transcriptional regulator C/EBP
      homologous protein (CHOP; GADD153/DDIT3). We determined that UVB irradiation is a
      potent inducer of eIF2-P in keratinocytes, leading to decreased levels of
      translation initiation. However, expression of ATF4 or CHOP was not induced by
      UVB as compared with traditional ISR activators. The rationale for this
      discordant response is that ATF4 mRNA is reduced by UVB, and despite its ability
      to be preferentially translated, there are diminished levels of available
      transcript. Forced expression of ATF4 and CHOP protein before UVB irradiation
      significantly enhanced apoptosis, suggesting that this portion of the ISR is
      deleterious in keratinocytes following UVB. Inhibition of eIF2-P and
      translational control reduced viability following UVB that was alleviated by
      cycloheximide (CHX), indicating that translation repression through eIF2-P is
      central to keratinocyte survival. 

PMID- 25950826
TI  - Evaluation of Repigmentation with Cultured Melanocyte Transplantation (CMT)
      Compared with Non-Cultured Epidermal Cell Transplantation in Vitiligo at 12th
      Week Reveals Better Repigmentation with CMT.

PMID- 25950828
TI  - Magnetic spin moment reduction in photoexcited ferromagnets through exchange
      interaction quenching: beyond the rigid band approximation.
AB  - The exchange interaction among electrons is one of the most fundamental quantum
      mechanical interactions in nature and underlies any magnetic phenomena from
      ferromagnetic ordering to magnetic storage. The current technology is built upon
      a thermal or magnetic field, but a frontier is emerging to directly control
      magnetism using ultrashort laser pulses. However, little is known about the fate
      of the exchange interaction. Here we report unambiguously that photoexcitation is
      capable of quenching the exchange interaction in all three 3d ferromagnetic
      metals. The entire process starts with a small number of photoexcited electrons
      which build up a new and self-destructive potential that collapses the system
      into a new state with a reduced exchange splitting. The spin moment reduction
      follows a Bloch-like law as M(z)(DeltaE) = M(z)(0)(1 - DeltaE/DeltaE0)(1/beta),
      where DeltaE is the absorbed photon energy and beta is a scaling exponent. A good
      agreement is found between the experimental and our theoretical results. Our
      findings may have a broader implication for dynamic electron correlation effects
      in laser-excited iron-based superconductors, iron borate, rare-earth
      orthoferrites, hematites and rare-earth transition metal alloys.

PMID- 25950827
TI  - Identification of Genes Expressed in Hyperpigmented Skin Using Meta-Analysis of
      Microarray Data Sets.
AB  - More than 375 genes have been identified that are involved in regulating skin
      pigmentation and these act during development, survival, differentiation, and/or
      responses of melanocytes to the environment. Many of these genes have been
      cloned, and disruptions of their functions are associated with various pigmentary
      diseases; however, many remain to be identified. We have performed a series of
      microarray analyses of hyperpigmented compared with less pigmented skin to
      identify genes responsible for these differences. The rationale and goal for this
      study was to perform a meta-analysis on these microarray databases to identify
      genes that may be significantly involved in regulating skin phenotype either
      directly or indirectly that might not have been identified due to subtle
      differences by any of these individual studies alone. The meta-analysis
      demonstrates that 1,271 probes representing 921 genes are differentially
      expressed at significant levels in the 5 microarray data sets compared, providing
      new insights into the variety of genes involved in determining skin phenotype.
      Immunohistochemistry was used to validate two of these markers at the protein
      level (TRIM63 and QPCT), and we discuss the possible functions of these genes in
      regulating skin physiology. 

PMID- 25950829
TI  - Molecular characterization of arginine deiminase pathway in Laribacter
      hongkongensis and unique regulation of arginine catabolism and anabolism by
      multiple environmental stresses.
AB  - The betaproteobacterium Laribacter hongkongensis is associated with invasive
      bacteremic infections and gastroenteritis. Its genome contains two adjacent arc
      gene cassettes (arc1 and arc2) under independent transcriptional control, which
      are essential for acid resistance. Laribacter hongkongensis also encodes
      duplicate copies of the argA and argB genes from the arginine biosynthesis
      pathway. We show that arginine enhances the transcription of arcA2 but suppresses
      arcA1 expression. We demonstrate that ArgR acts as a transcriptional regulator of
      the two arc operons through binding to ARG operator sites (ARG boxes). Upon
      temperature shift from 20 degrees C to 37 degrees C, arcA1 transcription is
      upregulated while arcA2, argA2, argB2 and argG are downregulated. The
      transcription of arcA1 and arcA2 are augmented under anaerobic and acidic
      conditions. The transcription levels of argA1, argA2, argB1, argB2 and argG are
      significantly increased under anaerobic and acidic conditions but are repressed
      by the addition of arginine. Deletion of argR significantly decreases bacterial
      survival in macrophages, while expression of both arc operons, argR and all five
      of the anabolic arg genes increases 8 h post-infection. Our results show that
      arginine catabolism in L. hongkongensis is finely regulated by controlling the
      transcription of two arc operons, whereas arginine anabolism is controlled by two
      copies of argA and argB. 

PMID- 25950830
TI  - Correction: Isolation of phages for phage therapy: a comparison of spot tests and
      efficiency of plating analyses for determination of host range and efficacy.

PMID- 25950831
TI  - Elusive Critical Elements of Transformative Risk Assessment Practice and
      Interpretation: Is Alternatives Analysis the Next Step?
AB  - This article argues that "game-changing" approaches to risk analysis must focus
      on "democratizing" risk analysis in the same way that information technologies
      have democratized access to, and production of, knowledge. This argument is
      motivated by the author's reading of Goble and Bier's analysis, "Risk Assessment
      Can Be a Game-Changing Information Technology-But Too Often It Isn't" (Risk
      Analysis, 2013; 33: 1942-1951), in which living risk assessments are shown to be
      "game changing" in probabilistic risk analysis. In this author's opinion, Goble
      and Bier's article focuses on living risk assessment's potential for transforming
      risk analysis from the perspective of risk professionals-yet, the game-changing
      nature of information technologies has typically achieved a much broader reach.
      Specifically, information technologies change who has access to, and who can
      produce, information. From this perspective, the author argues that risk
      assessment is not a game-changing technology in the same way as the printing
      press or the Internet because transformative information technologies reduce the
      cost of production of, and access to, privileged knowledge bases. The author
      argues that risk analysis does not reduce these costs. The author applies Goble
      and Bier's metaphor to the chemical risk analysis context, and in doing so
      proposes key features that transformative risk analysis technology should
      possess. The author also discusses the challenges and opportunities facing risk
      analysis in this context. These key features include: clarity in information
      structure and problem representation, economical information dissemination,
      increased transparency to nonspecialists, democratized manufacture and
      transmission of knowledge, and democratic ownership, control, and interpretation
      of knowledge. The chemical safety decision-making context illustrates the impact
      of changing the way information is produced and accessed in the risk context.
      Ultimately, the author concludes that although new chemical safety regulations do
      transform access to risk information, they do not transform the costs of
      producing this information-rather, they change the bearer of these costs. The
      need for further risk assessment transformation continues to motivate new
      practical and theoretical developments in risk analysis and management. 

PMID- 25950832
TI  - Initial data on the molecular epidemiology of cryptosporidiosis in Lebanon.
AB  - Cryptosporidium spp. represent a major public health problem worldwide and infect
      the gastrointestinal tract of both immunocompetent and immunocompromised persons.
      The prevalence of these parasites varies by geographic region, and no data are
      currently available in Lebanon. To promote an understanding of the epidemiology
      of cryptosporidiosisin this country, the main aim of this study was to determine
      the prevalence Cryptosporidium in symptomatic hospitalized patients, and to
      analyze the genetic diversity of the corresponding isolates. Fecal specimens were
      collected in four hospitals in North Lebanon from 163 patients (77 males and 86
      females, ranging in age from 1 to 88 years, with a mean age of 22 years)
      presenting gastrointestinal disorders during the period July to December 2013.
      The overall prevalence of Cryptosporidium spp. infection obtained by modified
      Ziehl-Neelsen staining and/or nested PCR was 11%, and children <5 years old
      showed a higher rate of Cryptosporidium spp. The PCR products of the 15 positive
      samples were successfully sequenced. Among them, 10 isolates (66.7%) were
      identified as C. hominis, while the remaining 5 (33.3%) were identified as C.
      parvum. After analysis of the gp60 locus, C. hominis IdA19, a rare subtype, was
      found to be predominant. Two C. parvum subtypes were found: IIaA15G1R1 and
      IIaA15G2R1. The molecular characterization of Cryptosporidium isolates is an
      important step in improving our understanding of the epidemiology and
      transmission of the infection. 

PMID- 25950833
TI  - Measuring pragmatic skills: early detection of infants at risk for communication
      problems.
AB  - BACKGROUND: For the early detection of children who are at risk of communication
      problems, we need appropriate assessment instruments. Two Dutch-language
      standardised screening instruments are available: the Dutch version of the Non
      Speech Test (NNST) and the Dutch version of the MacArthur Communicative
      Development Inventories (N-CDIs). These instruments gauge the precursors of
      language development, early vocabulary and early morphosyntactic skills. However,
      they do not adequately assess pragmatic skills. AIMS: To develop a norm
      referenced instrument to examine the pragmatic skills of Dutch-speaking infants
      that is translatable into other languages. METHODS & PROCEDURES: The instrument
      'Lists for the Evaluation of Pragmatic Skills in Infants' is based on 'The
      Pragmatics Profile of Everyday Communication Skills in Children' Dewart and
      Summers (1995). We translated the instrument into Dutch and transformed the
      structured interview format into a parent questionnaire. The parent questionnaire
      Evaluatie van Pragmatische Vaardigheden (EPV)-was created following extensive
      research on item selection, norm table development, and reliability and validity
      studies. The EPV1 is applicable to children 6-15 months old; EPV2 is applicable
      to children 16-30 months old. OUTCOMES & RESULTS: We developed norm tables for
      the number of pragmatic skills achieved by the child and also for how and to what
      extent the skills are exhibited. For the norming study of EPV1 and EPV2 we
      included 390 and 534 infants respectively. The reliability scores are high for
      both lists. Concept validity and criterion validity studies demonstrate adequate
      results for the overall lists, the subscale components and specific items.
      CONCLUSIONS & IMPLICATIONS: The parent questionnaire is a valuable tool that
      specifically targets pragmatic skills in infants. The instrument can detect
      communication delays in infants. It is translatable into other languages and
      avoids having the infant examined directly by a stranger.

PMID- 25950834
TI  - Reprogramming LCLs to iPSCs Results in Recovery of Donor-Specific Gene Expression
      Signature.
AB  - Renewable in vitro cell cultures, such as lymphoblastoid cell lines (LCLs), have
      facilitated studies that contributed to our understanding of genetic influence on
      human traits. However, the degree to which cell lines faithfully maintain
      differences in donor-specific phenotypes is still debated. We have previously
      reported that standard cell line maintenance practice results in a loss of donor
      specific gene expression signatures in LCLs. An alternative to the LCL model is
      the induced pluripotent stem cell (iPSC) system, which carries the potential to
      model tissue-specific physiology through the use of differentiation protocols.
      Still, existing LCL banks represent an important source of starting material for
      iPSC generation, and it is possible that the disruptions in gene regulation
      associated with long-term LCL maintenance could persist through the reprogramming
      process. To address this concern, we studied the effect of reprogramming mature
      LCL cultures from six unrelated donors to iPSCs on the ensuing gene expression
      patterns within and between individuals. We show that the reprogramming process
      results in a recovery of donor-specific gene regulatory signatures, increasing
      the number of genes with a detectable donor effect by an order of magnitude. The
      proportion of variation in gene expression statistically attributed to donor
      increases from 6.9% in LCLs to 24.5% in iPSCs (P < 10-15). Since environmental
      contributions are unlikely to be a source of individual variation in our system
      of highly passaged cultured cell lines, our observations suggest that the effect
      of genotype on gene regulation is more pronounced in iPSCs than in LCLs. Our
      findings indicate that iPSCs can be a powerful model system for studies of
      phenotypic variation across individuals in general, and the genetic association
      with variation in gene regulation in particular. We further conclude that LCLs
      are an appropriate starting material for iPSC generation. 

PMID- 25950835
TI  - A wind-powered BDD electrochemical oxidation process for the removal of
      herbicides.
AB  - In the search for greener treatment technologies, this work studies the coupling
      of a wind turbine energy supply with an electrolytic cell (CWTEC device) for the
      remediation of wastewater polluted with pesticide 2,4-dichlorophenoxyacetic acid
      (2,4-D). The discontinuous and unforeseeable supply of energy is the main
      challenge inspiring this new proposal, which aims at reducing the environmental
      impact of electrolytic treatment by using a green energy supply. The results
      obtained using the coupled technologies are compared with those obtained by
      powering the electrolyser with a traditional power supply with a similar current
      intensity. The mineralisation of wastewater can be accomplished independently of
      how the electrolytic cell is powered, although differences in performance are
      clearly observed in the total organic carbon (TOC) and 2,4-D decays. These
      changes can be explained in terms of the changing profile of the current
      intensity, which influences the concentrations of the oxidants produced and
      thereby the mediated electrolytic process. 

PMID- 25950836
TI  - Case study of a non-destructive treatment method for the remediation of military
      structures containing polychlorinated biphenyl contaminated paint.
AB  - Restricted by federal regulations and limited remediation options, buildings
      contaminated with paint laden with polychlorinated biphenyls (PCBs) have high
      costs associated with the disposal of hazardous materials. As opposed to current
      remediation methods which are often destructive and a risk to the surrounding
      environment, this study suggests a non-metal treatment system (NMTS) and a
      bimetallic treatment system (BTS) as versatile remediation options for painted
      industrial structures including concrete buildings, and metal machine parts. In
      this field study, four areas of a discontinued Department of Defense site were
      treated and monitored over 3 weeks. PCB levels in paint and treatment system
      samples were analyzed through gas chromatography/electron capture detection (GC
      ECD). PCB concentrations were reduced by 95 percent on painted concrete and by 60
      97 percent on painted metal with the majority of the PCB removal occurring within
      the first week of application. Post treatment laboratory studies including the
      utilization of an activated metal treatment system (AMTS) further degraded PCBs
      in BTS and NMTS by up to 82 percent and 99 percent, respectively, indicating that
      a two-step remediation option is viable. These findings demonstrate that the NMTS
      and BTS can be an effective, nondestructive, remediation process for large
      painted structures, allowing for the reuse or sale of remediated materials that
      otherwise may have been disposed. 

PMID- 25950837
TI  - Stenting for malignant ureteral obstruction: Tandem, metal or metal-mesh stents.
AB  - Extrinsic malignant compression of the ureter is not uncommon, often refractory
      to decompression with conventional polymeric ureteral stents, and frequently
      associated with limited survival. Alternative options for decompression include
      tandem ureteral stents, metallic stents and metal-mesh stents, though the
      preferred method remains controversial. We reviewed and updated our outcomes with
      tandem ureteral stents for malignant ureteral obstruction, and carried out a
      PubMed search using the terms "malignant ureteral obstruction," "tandem ureteral
      stents," "ipsilateral ureteral stents," "metal ureteral stent," "resonance
      stent," "silhouette stent" and "metal mesh stent." A comprehensive review of the
      literature and summary of outcomes is provided. The majority of studies
      encountered were retrospective with small sample sizes. The evidence is most
      robust for metal stents, whereas only limited data exists for tandem or metal
      mesh stents. Metal and metal-mesh stents are considerably more expensive than
      tandem stenting, but the potential for less frequent stent exchanges makes them
      possibly cost-effective over time. Urinary tract infections have been associated
      with all stent types. A wide range of failure rates has been published for all
      types of stents, limiting direct comparison. Metal and metal-mesh stents show a
      high incidence of stent colic, migration and encrustation, whereas tandem stents
      appear to produce symptoms equivalent to single stents. Comparison is difficult
      given the limited evidence and heterogeneity of patients with malignant ureteral
      obstruction. It is clear that prospective, randomized studies are necessary to
      effectively scrutinize conventional, tandem, metallic ureteral and metal-mesh
      stents for their use in malignant ureteral obstruction. 

PMID- 25950838
TI  - Validation of the Chinese version of the Quality of Nursing Work Life scale.
AB  - Quality of Nursing Work Life (QNWL) serves as a predictor of a nurse's intent to
      leave and hospital nurse turnover. However, QNWL measurement tools that have been
      validated for use in China are lacking. The present study evaluated the construct
      validity of the QNWL scale in China. A cross-sectional study was conducted
      conveniently from June 2012 to January 2013 at five hospitals in Guangzhou, which
      employ 1938 nurses. The participants were asked to complete the QNWL scale and
      the World Health Organization Quality of Life abbreviated version (WHOQOL-BREF).
      A total of 1922 nurses provided the final data used for analyses. Sixty-five
      nurses from the first investigated division were re-measured two weeks later to
      assess the test-retest reliability of the scale. The internal consistency
      reliability of the QNWL scale was assessed using Cronbach's alpha. Test-retest
      reliability was assessed using the intra-class correlation coefficient (ICC).
      Criterion-relation validity was assessed using the correlation of the total
      scores of the QNWL and the WHOQOL-BREF. Construct validity was assessed with the
      following indices: chi2 statistics and degrees of freedom; relative mean square
      error of approximation (RMSEA); the Akaike information criterion (AIC); the
      consistent Akaike information criterion (CAIC); the goodness-of-fit index (GFI);
      the adjusted goodness of fit index; and the comparative fit index (CFI). The
      findings demonstrated high internal consistency (Cronbach's alpha = 0.912) and
      test-retest reliability (interclass correlation coefficient = 0.74) for the QNWL
      scale. The chi-square test (chi2 = 13879.60, df [degree of freedom] = 813 P =
      0.0001) was significant. The RMSEA value was 0.091, and AIC = 1806.00, CAIC =
      7730.69, CFI = 0.93, and GFI = 0.74. The correlation coefficient between the QNWL
      total scores and the WHOQOL-BREF total scores was 0.605 (p<0.01). The QNWL scale
      was reliable and valid in Chinese-speaking nurses and could be used as a clinical
      and research instrument for measuring work-related factors among nurses in China.

PMID- 25950839
TI  - Relating Pupil Dilation and Metacognitive Confidence during Auditory Decision
      Making.
AB  - The sources of evidence contributing to metacognitive assessments of confidence
      in decision-making remain unclear. Previous research has shown that pupil
      dilation is related to the signaling of uncertainty in a variety of decision
      tasks. Here we ask whether pupil dilation is also related to metacognitive
      estimates of confidence. Specifically, we measure the relationship between pupil
      dilation and confidence during an auditory decision task using a general linear
      model approach to take into account delays in the pupillary response. We found
      that pupil dilation responses track the inverse of confidence before but not
      after a decision is made, even when controlling for stimulus difficulty. In
      support of an additional post-decisional contribution to the accuracy of
      confidence judgments, we found that participants with better metacognitive
      ability - that is, more accurate appraisal of their own decisions - showed a
      tighter relationship between post-decisional pupil dilation and confidence.
      Together our findings show that a physiological index of uncertainty, pupil
      dilation, predicts both confidence and metacognitive accuracy for auditory
      decisions. 

PMID- 25950840
TI  - Effect of mesenchymal precursor cells on the systemic inflammatory response and
      endothelial dysfunction in an ovine model of collagen-induced arthritis.
AB  - BACKGROUND AND AIM: Mesenchymal precursor cells (MPC) are reported to possess
      immunomodulatory properties that may prove beneficial in autoimmune and other
      inflammatory conditions. However, their mechanism of action is poorly understood.
      A collagen-induced arthritis model has been previously developed which
      demonstrates local joint inflammation and systemic inflammatory changes. These
      include not only increased levels of inflammatory markers, but also vascular
      endothelial cell dysfunction, characterised by reduced endothelium-dependent
      vasodilation. This study aimed to characterise the changes in systemic
      inflammatory markers and endothelial function following the intravenous
      administration of MPC, in the ovine model. METHODS: Arthritis was induced in
      sixteen adult sheep by administration of bovine type II collagen into the hock
      joint following initial sensitisation. After 24h, sheep were administered either
      150 million allogeneic ovine MPCs intravenously, or saline only. Fibrinogen and
      serum amyloid-A were measured in plasma to assess systemic inflammation, along
      with pro-inflammatory and anti-inflammatory cytokines. Animals were necropsied
      two weeks following arthritis induction. Coronary and digital arterial segments
      were mounted in a Mulvaney-Halpern wire myograph. The relaxant response to
      endothelium-dependent and endothelium-independent vasodilators was used to assess
      endothelial dysfunction. RESULTS AND CONCLUSION: Arthritic sheep treated with MPC
      demonstrated a marked spike in plasma IL-10, 24h following MPC administration.
      They also showed significantly reduced plasma levels of the inflammatory markers,
      fibrinogen and serum amyloid A, and increased HDL. Coronary arteries from RA
      sheep treated with MPCs demonstrated a significantly greater maximal relaxation
      to bradykinin when compared to untreated RA sheep (253.6 +/- 17.1% of pre
      contracted tone vs. 182.3 +/- 27.3% in controls), and digital arteries also
      demonstrated greater endothelium-dependent vasodilation. This study demonstrated
      that MPCs given intravenously are able to attenuate systemic inflammatory changes
      associated with a monoarthritis, including the development of endothelial
      dysfunction.

PMID- 25950841
TI  - Endoplasmic reticulum-Golgi complex membrane contact sites.
AB  - Although they were identified as long ago as the 1960s, there are still many
      unknowns regarding the functions and composition of membrane contact sites
      between the endoplasmic reticulum (ER) and the trans-Golgi (TG). While it seems
      to be fairly well established that they facilitate lipid exchange between the two
      organelles, much less is known about how they are regulated. A bottleneck in the
      study of the ER-TG contact sites has been the absence of methods for their
      biochemical isolation and visualization by light microscopy. Herein we provide an
      overview of current knowledge about ER-TG contact sites with a particular
      emphasis on the questions that remain to be explored. 

PMID- 25950842
TI  - Midbody: from cellular junk to regulator of cell polarity and cell fate.
AB  - At late mitosis, the mother cell divides by the formation of a cleavage furrow,
      leaving two daughter cells connected by a thin intercellular bridge. During
      ingression of the cleavage furrow, the central spindle microtubules are compacted
      to form the structure known as the midbody (MB). The MB is situated within the
      intercellular bridge, with the abscission site sometimes occurring on one side of
      the MB. As a result of this one-sided (asymmetric) abscission, only one daughter
      cell can inherit the post-mitotic MB. Interestingly, recent studies have
      identified post-mitotic MBs as novel signaling platforms regulating stem cell
      fate and proliferation. Additionally, MBs were proposed to serve a role of
      polarity cues during the neurite outgrowth and apical lumen formation. Thus,
      abscission and MB inheritance is clearly a highly regulated cellular event that
      can affect development and various other cellular functions. In this review we
      discuss the latest findings regarding post-mitotic MB functions, as well as the
      machinery regulating MB inheritance and accumulation. 

PMID- 25950844
TI  - Comment on "Broadband Criticality of Human Brain Network Synchronization" by
      Kitzbichler MG, Smith ML, Christensen SR, Bullmore E (2009) PLoS Comput Biol 5:
      e1000314.

PMID- 25950843
TI  - Beyond indigestion: emerging roles for lysosome-based signaling in human disease.
AB  - Lysosomes are becoming increasingly recognized as a hub that integrates diverse
      signals in order to control multiple aspects of cell physiology. This is
      illustrated by the discovery of a growing number of lysosome-localized proteins
      that respond to changes in growth factor and nutrient availability to regulate
      mTORC1 signaling as well as the identification of MiT/TFE transcription factors
      (MITF, TFEB and TFE3) as proteins that shuttle between lysosomes and the nucleus
      to elicit a transcriptional response to ongoing changes in lysosome status. These
      findings have been paralleled by advances in human genetics that connect
      mutations in genes involved in lysosomal signaling to a broad range of human
      illnesses ranging from cancer to neurological disease. This review summarizes
      these new discoveries at the interface between lysosome cell biology and human
      disease. 

PMID- 25950846
TI  - Fabrication of zeolite/polymer multilayer composite membranes for carbon dioxide
      capture: Deposition of zeolite particles on polymer supports.
AB  - Membranes, due to their smaller footprint and potentially lower energy
      consumption than the amine process, offer a promising route for post-combustion
      CO2 capture. Zeolite Y based inorganic selective layers offer a favorable
      combination of CO2 permeance and CO2/N2 selectivity, membrane properties crucial
      to the economics. For economic viability on large scale, we propose to use
      flexible and scalable polymer supports for inorganic selective layers. The work
      described in this paper developed a detailed protocol for depositing thin zeolite
      Y seed layers on polymer supports, the first step in the synthesis of a
      polycrystalline zeolite Y membrane. We also studied the effects of support
      surface morphology (pore size and surface porosity) on the quality of deposition
      and identified favorable supports for the deposition. Two different zeolite Y
      particles with nominal sizes of 200 nm and 40 nm were investigated. To obtain a
      complete coverage of zeolite particles on the support surface with minimum
      defects and in a reproducible manner, a vacuum-assisted dip-coating technique was
      developed. Images obtained using both digital camera and optical microscope
      showed the presence of color patterns on the deposited surface which suggested
      that the coverage was complete. Electron microscopy revealed that the particle
      packing was dense with some drying cracks. Layer thickness with the larger
      zeolite Y particles was close to 1 MUm while that with the smaller particles was
      reduced to less than 0.5 MUm. In order to reduce drying cracks for layers with
      smaller zeolite Y particles, thickness was reduced by lowering the dispersion
      concentration. Transport measurement was used as an additional technique to
      characterize these layers.

PMID- 25950845
TI  - Incidence, Antibiotic Susceptibility, and Toxin Profiles of Bacillus cereus sensu
      lato Isolated from Korean Fermented Soybean Products.
AB  - Korean fermented soybean products, such as doenjang, kochujang, ssamjang, and cho
      kochujang, can harbor foodborne pathogens such as Bacillus cereus sensu lato (B.
      cereus sensu lato). The aim of this study was to characterize the toxin gene
      profiles, biochemical characteristics, and antibiotic resistance patterns of B.
      cereus sensu lato strains isolated from Korean fermented soybean products. Eighty
      eight samples of Korean fermented soybean products purchased from retails in
      Seoul were tested. Thirteen of 26 doenjang samples, 13 of 23 kochujang samples,
      16 of 30 ssamjang samples, and 5 of 9 cho-kochujang samples were positive for B.
      cereus sensu lato strains. The contamination level of all positive samples did
      not exceed 4 log CFU/g of food (maximum levels of Korea Food Code). Eighty-seven
      B. cereus sensu lato strains were isolated from 47 positive samples, and all
      isolates carried at least one enterotoxin gene. The detection rates of hblCDA,
      nheABC, cytK, and entFM enterotoxin genes among all isolates were 34.5%, 98.9%,
      57.5%, and 100%, respectively. Fifteen strains (17.2%) harbored the emetic toxin
      gene. Most strains tested positive for salicin fermentation (62.1%), starch
      hydrolysis (66.7%), hemolysis (98.9%), motility test (100%), and lecithinase
      production (96.6%). The B. cereus sensu lato strains were highly resistant to
      beta-lactam antibiotics such as ampicillin, penicillin, cefepime, imipenem, and
      oxacillin. Although B. cereus sensu lato levels in Korean fermented soybean
      products did not exceed the maximum levels permitted in South Korea (<10(4)
      CFU/g), these results indicate that the bacterial isolates have the potential to
      cause diarrheal or emetic gastrointestinal diseases. 

PMID- 25950847
TI  - IL-1 signaling inhibits Trichophyton rubrum conidia development and modulates the
      IL-17 response in vivo.
AB  - Dermatophytosis are one of the most common fungal infections in the world. They
      compromise keratinized tissues and the main etiological agent is Trichophyton
      rubrum. Macrophages are key cells in innate immunity and prominent sources of IL
      1beta, a potent inflammatory cytokine whose main production pathway is by the
      activation of inflammasomes and caspase-1. However, the role of inflammasomes and
      IL-1 signaling against T.rubrum has not been reported. In this work, we observed
      that bone marrow-derived macrophages produce IL-1beta in response to T.rubrum
      conidia in a NLRP3-, ASC- and caspase-1-dependent fashion. Curiously, lack of IL
      1 signaling promoted hyphae development, uncovering a protective role for IL
      1beta in macrophages. In addition, mice lacking IL-1R showed reduced IL-17
      production, a key cytokine in the antifungal defense, in response to T.rubrum.
      Our findings point to a prominent role of IL-1 signaling in the immune response
      to T.rubrum, opening the venue for the study of this pathway in other fungal
      infections. 

PMID- 25950850
TI  - Nanoscale Buckling of Ultrathin Low-k Dielectric Lines during Hard-Mask
      Patterning.
AB  - Commonly known in macroscale mechanics, buckling phenomena are now also
      encountered in the nanoscale world as revealed in today's cutting-edge
      fabrication of microelectronics. The description of nanoscale buckling requires
      precise dimensional and elastic moduli measurements, as well as a thorough
      understanding of the relationships between stresses in the system and the ensuing
      morphologies. Here, we analyze quantitatively the buckling mechanics of
      organosilicate fins that are capped with hard masks in the process of
      lithographic formation of deep interconnects. We propose an analytical model that
      quantitatively describes the morphologies of the buckled fins generated by
      residual stresses in the hard mask. Using measurements of mechanical properties
      and geometric characteristics, we have verified the predictions of the analytical
      model for structures with various degrees of buckling, thus putting forth a
      framework for guiding the design of future nanoscale interconnect architectures. 

PMID- 25950848
TI  - Treatment Modifications and Treatment-Limiting Toxicities or Side Effects: Risk
      Factors and Temporal Trends.
AB  - Combined antiretroviral treatment (cART) modifications are often required due to
      treatment failure or side effects. We investigate cART regimens' durability,
      frequency of treatment-limiting adverse events, and potential risk factors and
      temporal trends. Data were derived from the Athens Multicenter AIDS Cohort Study
      (AMACS). Statistical analyses were based on survival techniques, allowing for
      multiple contributions per individual. Overall, 2,756 individuals, aged >15
      years, initiated cART. cART regimens were grouped by their initiation date into
      four calendar periods (1995-1998, 1999-2002, 2003-2006, and 2007+). Median [95%
      confidence interval (CI)] time to first treatment modification was 2.11 (1.95
      2.33) years; cumulative probabilities at 1 year were 31.6%, 29.0%, 33.1%, and
      29.6% for the four periods, respectively. cART modifications were less frequent
      in more recent years (adjusted HR=0.96 per year; p<0.001). Longer treatment
      duration was associated with lower HIV-RNA, higher CD4 counts, and being
      previously ART naive. cART modifications due to treatment failure became less
      frequent in recent years (adjusted HR=0.91 per year; p<0.001). Estimated (95% CI)
      1 year cumulative probabilities of treatment-limiting side effects were 16.4%
      (12.0-21.3%), 19.3% (15.6-23.3%), 24.9% (20.3-29.7%), and 21.1% (13.4-29.9%) for
      the four periods, respectively, with no significant temporal trends. Risk of side
      effects was lower in nonnucleoside reverse transcriptase inhibitor (NNRTI)-based
      regimens or triple nucleoside reverse transcriptase inhibitor (NRTI)-based cART
      regimens. Treatment modifications have become less frequent in more recent years.
      This could be partly attributed to the lower risk for side effects of NNRTI-based
      cART regimens and mainly to the improved efficacy of newer drugs. However, the
      rate of drugs substitutions due to adverse events remains substantially high.

PMID- 25950849
TI  - Could machine learning improve the prediction of pelvic nodal status of prostate
      cancer patients? Preliminary results of a pilot study.
AB  - We tested and compared performances of Roach formula, Partin tables and of three
      Machine Learning (ML) based algorithms based on decision trees in identifying N+
      prostate cancer (PC). 1,555 cN0 and 50 cN+ PC were analyzed. Results were also
      verified on an independent population of 204 operated cN0 patients, with a known
      pN status (187 pN0, 17 pN1 patients). ML performed better, also when tested on
      the surgical population, with accuracy, specificity, and sensitivity ranging
      between 48-86%, 35-91%, and 17-79%, respectively. ML potentially allows better
      prediction of the nodal status of PC, potentially allowing a better tailoring of
      pelvic irradiation. 

PMID- 25950851
TI  - Control of pathogens in biofilms on the surface of stainless steel by levulinic
      acid plus sodium dodecyl sulfate.
AB  - The efficacy of levulinic acid (LVA) plus sodium dodecyl sulfate (SDS) to remove
      or inactivate Listeria monocytogenes, Salmonella Typhimurium, and Shiga toxin
      producing Escherichia coli (STEC) in biofilms on the surface of stainless steel
      coupons was evaluated. Five- or six-strain mixtures (ca. 9.0 log CFU/ml) of the
      three pathogens were separately inoculated on stainless steel coupons. After
      incubation at 21  degrees C for 72 h, the coupons were treated for 10 min by
      different concentrations of LVA plus SDS (0.5% LVA+0.05% SDS, 1% LVA+0.1% SDS,
      and 3% LVA+2% SDS) and other commonly used sanitizers, including a commercial
      quaternary ammonium-based sanitizer (150 ppm), lactic acid (3%), sodium
      hypochlorite (100 ppm), and hydrogen peroxide (2%). The pathogens grew in the
      biofilms to ca. 8.6 to 9.3 log CFU/coupon after 72 h of incubation. The combined
      activity of LVA with SDS was bactericidal in biofilms for cells of the three
      pathogens evaluated, with the highest concentrations (3% LVA+2% SDS) providing
      the greatest log reduction. Microscopic images indicated that the cells were
      detached from the biofilm matrix and the integrity of cell envelopes were
      decreased after the treatment of LVA plus SDS. This study is conducive to better
      understanding the antimicrobial behavior of LVA plus SDS to the foodborne
      pathogens within biofilms.

PMID- 25950852
TI  - Reduction of Salmonella on chicken meat and chicken skin by combined or
      sequential application of lytic bacteriophage with chemical antimicrobials.
AB  - The effectiveness of recently approved Salmonella lytic bacteriophage preparation
      (SalmoFreshTM) in reducing Salmonella in vitro and on chicken breast fillets was
      examined in combination with lauric arginate (LAE) or cetylpyridinium chloride
      (CPC). In another experiment, a sequential spray application of this
      bacteriophage (phage) solution on Salmonella inoculated chicken skin after a 20s
      dip in chemical antimicrobials (LAE, CPC, peracetic acid, or chlorine) was also
      examined in reducing Salmonella counts on chicken skin. The application of phage
      in combination with CPC or LAE reduced S. Typhimurium, S. Heidelberg, and S.
      Enteritidis up to 5 log units in vitro at 4  degrees C. On chicken breast
      fillets, phage in combination with CPC or LAE resulted in significant (p<0.05)
      reductions of Salmonella ranging from 0.5 to 1.3 log CFU/g as compared to control
      up to 7 days of refrigerated storage. When phage was applied sequentially with
      chemical antimicrobials, all the treatments resulted in significant reductions of
      Salmonella. The application of chlorine (30 ppm) and PAA (400 ppm) followed by
      phage spray (10(9)PFU/ml) resulted in highest Salmonella reductions of 1.6-1.7
      and 2.2-2.5l og CFU/cm(2), respectively. In conclusion, the surface applications
      of phage in combination with LAE or CPC significantly reduced Salmonella counts
      on chicken breast fillets. However, higher reductions in Salmonella counts were
      achieved on chicken skin by the sequential application of chemical antimicrobials
      followed by phage spray. The sequential application of chlorine, PAA, and phage
      can provide additional hurdles to reduce Salmonella on fresh poultry carcasses or
      cut up parts.

PMID- 25950853
TI  - Activation of the chromosomally encoded mazEF(Bif) locus of Bifidobacterium
      longum under acid stress.
AB  - Toxin-antitoxin (TA) systems are distributed within the genomes of almost all
      free-living bacteria. Although the roles of chromosomally encoded TA systems are
      still under debate, they are suspected to be involved in various stress
      responses. Here, we provide the first report of a type II TA system in the
      probiotic bacterium Bifidobacterium longum. Bioinformatic analysis of the B.
      longum JDM301 genome identified a pair of linked genes encoding a MazEF-like TA
      system at the locus BLJ_811-BLJ_812. Our results showed that B. longum mazEF(Bif)
      genes form a bicistronic operon. The over-expression of MazF(Bif) was toxic to
      Escherichia coli and could be neutralized by the co-expression of its cognate
      antitoxin MazE(Bif). We demonstrated that MazEF(Bif) was activated during acid
      stress, which would most likely be encountered in the gastrointestinal tract. In
      addition, we found that the protease ClpPX(Bif), in addition to MazEF(Bif), was
      induced under acid stress. Furthermore, we examined antitoxin levels over time
      for MazEF(Bif) and observed that the antitoxin MazE(Bif) was degraded by
      ClpPX(Bif), which suggested that MazEF(Bif) was activated through the hydrolysis
      of MazE(Bif) by ClpP1X(Bif) and ClpP2X(Bif) under acid stress. Our results
      suggest that the MazEF(Bif) TA module may play an important role in cell
      physiology and may represent a cell growth modulator that helps bacteria to cope
      with acid stress in the gastrointestinal tract and environment. 

PMID- 25950855
TI  - Factors associated with drug survival of methotrexate and acitretin in patients
      with psoriasis.
AB  - Drug survival has recently become an important clinical issue in psoriasis.
      However, there has been little research into factors associated with drug
      survival of methotrexate and acitretin. The aim of this study was to investigate
      factors associated with drug survival of methotrexate and acitretin treatment for
      psoriasis. Survival analysis was performed in patients who received methotrexate
      or acitretin for the treatment of psoriasis, drawn from the Clalit Health
      Services database. Investigated factors included demographic variables, obesity,
      metabolic syndrome, psoriatic arthritis, administration route and folic acid
      supplementation. Among 6,256 patients, factors associated with treatment drop-out
      were: younger age (p <0.001) and psoriatic arthritis (acitretin p < 0.001). For
      methotrexate, metabolic syndrome (p = 0.033), intramuscular administration route
      of injection (p <0.001) and lack of folic acid supplementation (p <0.001) were
      associated with treatment drop-out. In patients with psoriasis, some ancillary
      factors may modify the drug survival of acitretin and methotrexate. 

PMID- 25950856
TI  - Correction: Strongly correlated plexcitonics: evolution of the Fano resonance in
      the presence of Kondo correlations.

PMID- 25950857
TI  - A Chiral, Photoluminescent, and Spin-Canted {Cu(I)Re(IV)2}n Branched Chain.
AB  - A new heteroleptic 1D Cu(I)-Re(IV) coordination polymer of the formula
      {Cu(I)Re(IV)Cl4(MU-Cl)(MU-pyz)[Re(IV)Cl4(MU-bpym)]}n.nMeNO2 (1; pyz = pyrazine,
      bpym = 2,2'-bipyrimidine) has been prepared through the Cu(I)-mediated self
      assembly of two different Re(IV) metalloligands, namely, [ReCl5(pyz)](-) and
      [ReCl4(bpym)]. 1 consists of chiral branched chains with an overall rack-type
      architecture displaying photoemission and magnetic ordering. These results
      constitute a first step toward making new multifunctional magnetic materials
      based on mixed 3d-5d molecular systems. 

PMID- 25950858
TI  - Unraveling the Pathophysiology of the Asthma-COPD Overlap Syndrome: Unsuspected
      Mild Centrilobular Emphysema Is Responsible for Loss of Lung Elastic Recoil in
      Never Smokers With Asthma With Persistent Expiratory Airflow Limitation.
AB  - Investigators believe most patients with asthma have reversible airflow
      obstruction with treatment, despite airway remodeling and hyperresponsiveness.
      There are smokers with chronic expiratory airflow obstruction despite treatment
      who have features of both asthma and COPD. Some investigators refer to this
      conundrum as the asthma-COPD overlap syndrome (ACOS). Furthermore, a subset of
      treated nonsmokers with moderate to severe asthma have persistent expiratory
      airflow limitation, despite partial reversibility. This residuum has been assumed
      to be due to large and especially small airway remodeling. Alternatively, we and
      others have described reversible loss of lung elastic recoil in acute and
      persistent loss in patients with moderate to severe chronic asthma who never
      smoked and its adverse effect on maximal expiratory airflow. The mechanism(s)
      responsible for loss of lung elastic recoil and persistent expiratory airflow
      limitation in nonsmokers with chronic asthma consistent with ACOS remain unknown
      in the absence of structure-function studies. Recently we reported a new
      pathophysiologic observation in 10 treated never smokers with asthma with
      persistent expiratory airflow obstruction, despite partial reversibility: All 10
      patients with asthma had a significant decrease in lung elastic recoil, and
      unsuspected, microscopic mild centrilobular emphysema was noted in all three
      autopsies obtained although it was not easily identified on lung CT scan. These
      sentinel pathophysiologic observations need to be confirmed to further unravel
      the epiphenomenon of ACOS. The proinflammatory and proteolytic mechanism(s)
      leading to lung tissue breakdown need to be further investigated. 

PMID- 25950859
TI  - The impact of compliance in posttreatment surveillance in head and neck squamous
      cell carcinoma.
AB  - IMPORTANCE: Posttreatment surveillance (PTS) is a key component in the treatment
      of patients with head and neck cancer. It is unclear how beneficial this is in
      improving patients' survival. OBJECTIVE: To determine how compliance with follow
      up affects clinical outcomes in patients with head and neck squamous cell
      carcinoma. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort
      study at a tertiary academic center of a total of 332 patients with head and neck
      squamous cell carcinoma who had completed both treatment and follow-up at the
      University of Kansas Medical Center. Patient and tumor characteristics,
      socioeconomic status, and geographic data were collected. EXPOSURES: Compliance
      with PTS. MAIN OUTCOMES AND MEASURES: The effect of compliance with PTS on
      overall survival. RESULTS: Compliance with PTS, US Census tract income level, and
      the distance patients travel for follow-up had significant effects on survival (P
      = .001, P = .001, and P = .01, respectively). Cox proportional hazard models
      revealed that more advanced disease (hazard ratio [HR], 1.76 [95% CI, 1.21-2.58];
      P = .003), middle (HR, 1.64 [95% CI, 1.13-2.39]; P = .009) and moderate (HR, 1.90
      [95% CI, 1.18-3.06]; P = .008) census tract income level, and age (HR, 1.03 [95%
      CI, 1.01-1.04]; P < .001), were significantly associated with an increased risk
      of death. There was an association between compliance and tobacco cessation (P =
      .003), as well as the distance a patient lived from the medical center (P =
      .008). CONCLUSIONS AND RELEVANCE: Patients with head and neck squamous cell
      carcinoma were significantly more likely to survive with completion of follow-up
      and tobacco cessation. Compliance with PTS was associated with smoking cessation
      and traveling less than 200 miles for follow-up.

PMID- 25950861
TI  - Atypical Fractures are Mainly Subtrochanteric in Singapore and Diaphyseal in
      Sweden: A Cross-Sectional Study.
AB  - We have previously noted a dichotomy in the location of atypical fractures along
      the femoral shaft in Swedish patients, and a mainly subtrochanteric location of
      atypical fractures in descriptions of patients from Singapore. These unexpected
      differences were now investigated by testing the following hypotheses in a cross
      sectional study: first, that there is a dichotomy also in Singapore; second, that
      the relation between subtrochanteric and diaphyseal location is different between
      the two countries; third, that the location is related to femoral bow. The
      previously published Swedish sample (n = 151) was re-measured, and a new
      Singaporean sample (n = 75) was established. Both samples were based on
      radiographic classification of all femoral fractures in women above 55 years of
      age. The distance between the fracture line and the lesser trochanter was
      measured. Femoral bow was classified as present or absent on frontal radiographs.
      Frequency distribution of the measured distances was analyzed using the Bayesian
      information criterion to choose the best description of the observed variable
      distribution in terms of a compilation of normally distributed subgroups. The
      analysis showed a clear dichotomy of the fracture location: either
      subtrochanteric or diaphyseal. Subtrochanteric fractures comprised 48% of all
      fractures in Singapore, and 17% in Sweden (p = 0.0001). In Singapore, femoral bow
      was associated with more fractures in the diaphyseal subgroup (p = 0.0001). This
      was not seen in Sweden. A dichotomous location of atypical fractures was
      confirmed, because it was found also in Singapore. The fractures showed a
      different localization pattern in the two countries. This difference may be
      linked to anatomical variations, but might also be related to cultural
      differences between the two populations that influence physical activity.

PMID- 25950860
TI  - Polycaprolactone Thin-Film Micro- and Nanoporous Cell-Encapsulation Devices.
AB  - Cell-encapsulating devices can play an important role in advancing the types of
      tissue available for transplantation and further improving transplant success
      rates. To have an effective device, encapsulated cells must remain viable,
      respond to external stimulus, and be protected from immune responses, and the
      device itself must elicit a minimal foreign body response. To address these
      challenges, we developed a micro- and a nanoporous thin-film cell encapsulation
      device from polycaprolactone (PCL), a material previously used in FDA-approved
      biomedical devices. The thin-film device construct allows long-term
      bioluminescent transfer imaging, which can be used for monitoring cell viability
      and device tracking. The ability to tune the microporous and nanoporous membrane
      allows selective protection from immune cell invasion and cytokine-mediated cell
      death in vitro, all while maintaining typical cell function, as demonstrated by
      encapsulated cells' insulin production in response to glucose stimulation. To
      demonstrate the ability to track, visualize, and monitor the viability of cells
      encapsulated in implanted thin-film devices, we encapsulated and implanted
      luciferase-positive MIN6 cells in allogeneic mouse models for up to 90 days. Lack
      of foreign body response in combination with rapid neovascularization around the
      device shows promise in using this technology for cell encapsulation. These
      devices can help elucidate the metrics required for cell encapsulation success
      and direct future immune-isolation therapies. 

PMID- 25950862
TI  - A polynomial hyperelastic model for the mixture of fat and glandular tissue in
      female breast.
AB  - In the breast of adult women, glandular and fat tissues are intermingled and
      cannot be clearly distinguished. This work studies if this mixture can be treated
      as a homogenized tissue. A mechanical model is proposed for the mixture of
      tissues as a function of the fat content. Different distributions of individual
      tissues and geometries have been tried to verify the validity of the mixture
      model. A multiscale modelling approach was applied in a finite element model of a
      representative volume element (RVE) of tissue, formed by randomly assigning fat
      or glandular elements to the mesh. Both types of tissues have been assumed as
      isotropic, quasi-incompressible hyperelastic materials, modelled with a
      polynomial strain energy function, like the homogenized model. The RVE was
      subjected to several load cases from which the constants of the polynomial
      function of the homogenized tissue were fitted in the least squares sense. The
      results confirm that the fat volume ratio is a key factor in determining the
      properties of the homogenized tissue, but the spatial distribution of fat is not
      so important. Finally, a simplified model of a breast was developed to check the
      validity of the homogenized model in a geometry similar to the actual one.

PMID- 25950863
TI  - Investigation of protein selectivity in multimodal chromatography using in silico
      designed Fab fragment variants.
AB  - In this study, a unique set of antibody Fab fragments was designed in silico and
      produced to examine the relationship between protein surface properties and
      selectivity in multimodal chromatographic systems. We hypothesized that
      multimodal ligands containing both hydrophobic and charged moieties would
      interact strongly with protein surface regions where charged groups and
      hydrophobic patches were in close spatial proximity. Protein surface property
      characterization tools were employed to identify the potential multimodal ligand
      binding regions on the Fab fragment of a humanized antibody and to evaluate the
      impact of mutations on surface charge and hydrophobicity. Twenty Fab variants
      were generated by site-directed mutagenesis, recombinant expression, and affinity
      purification. Column gradient experiments were carried out with the Fab variants
      in multimodal, cation-exchange, and hydrophobic interaction chromatographic
      systems. The results clearly indicated that selectivity in the multimodal system
      was different from the other chromatographic modes examined. Column retention
      data for the reduced charge Fab variants identified a binding site comprising
      light chain CDR1 as the main electrostatic interaction site for the multimodal
      and cation-exchange ligands. Furthermore, the multimodal ligand binding was
      enhanced by additional hydrophobic contributions as evident from the results
      obtained with hydrophobic Fab variants. The use of in silico protein surface
      property analyses combined with molecular biology techniques, protein expression,
      and chromatographic evaluations represents a previously undescribed and powerful
      approach for investigating multimodal selectivity with complex biomolecules.

PMID- 25950864
TI  - Occupational safety and health protections against Ebola virus disease.
AB  - Even as the Ebola epidemic is finally showing signs of remitting, controversy
      continues regarding the modes of disease transmission, the understanding of which
      necessarily dictates methods of prevention. The initial public health response to
      the epidemic was based on assumptions formed during previous outbreaks, and in
      the belief that transmission was restricted to direct "contact" with other
      infected patients. However, the current Ebola outbreak differed from previous
      experiences in its intensity of transmission, speed of spread, and fatality rate
      and was also particularly unforgiving on health workers occupationally infected.
      Even with these differences, however, other modes of transmission were not
      considered by public health authorities, thus denying both the hard-hit health
      worker populations and the wider public more protective guidance. International
      Labor Conventions require employers to provide a comprehensive safety program
      that anticipates work-related risks and specifies strategies for protection
      against them. Such a precautionary approach is recommended in future epidemic
      planning, especially where evidence regarding transmission is incomplete.

PMID- 25950865
TI  - Archaeal Lineages within the Human Microbiome: Absent, Rare or Elusive?
AB  - Archaea are well-recognized components of the human microbiome. However, they
      appear to be drastically underrepresented compared to the high diversity of
      bacterial taxa which can be found on various human anatomic sites, such as the
      gastrointestinal environment, the oral cavity and the skin. As our "microbial"
      view of the human body, including the methodological concepts used to describe
      them, has been traditionally biased on bacteria, the question arises whether our
      current knowledge reflects the actual ratio of archaea versus bacteria or whether
      we have failed so far to unravel the full diversity of human-associated archaea.
      This review article hypothesizes that distinct archaeal lineages within humans
      exist, which still await our detection. First, previously unrecognized taxa might
      be quite common but they have eluded conventional detection methods. Two recent
      prime examples are described that demonstrate that this might be the case for
      specific archaeal lineages. Second, some archaeal taxa might be overlooked
      because they are rare and/or in low abundance. Evidence for this exists for a
      broad range of phylogenetic lineages, however we currently do not know whether
      these sporadically appearing organisms are mere transients or important members
      of the so called "rare biosphere" with probably basic ecosystem functions.
      Lastly, evidence exists that different human populations harbor different
      archaeal taxa and/or the abundance and activity of shared archaeal taxa may
      differ and thus their impact on the overall microbiome. This research line is
      rather unexplored and warrants further investigation. While not recapitulating
      exhaustively all studies on archaeal diversity in humans, this review highlights
      pertinent recent findings that show that the choice of appropriate methodological
      approaches and the consideration of different human populations may lead to the
      detection of archaeal lineages previously not associated with humans. This in
      turn will help understand variations found in the overall microbiomes from
      different individuals and ultimately may lead to the emergence of novel
      concepts/mechanisms impacting human health. 

PMID- 25950866
TI  - Uncultured Desulfobacteraceae and Crenarchaeotal group C3 incorporate 13C-acetate
      in coastal marine sediment.
AB  - Stable isotope probing (SIP) of deoxyribonucleic acid (DNA) was used to identify
      microbes incorporating (13) C-labeled acetate in sulfate-reducing sediment from
      Aarhus Bay, Denmark. Sediment was incubated in medium containing 10 mM sulfate
      and different (13) C-acetate (10, 1, 0.1 mM) concentrations. The resultant
      changes in microbial community composition were monitored in total and SIP
      fractionated DNA during long-term incubations. Chemical analyses demonstrated
      metabolic activity in all sediment slurries, with sulfate-reducing activity
      largely determined by initial acetate concentrations. Sequencing of 16S rRNA gene
      PCR amplicons showed that the incubations shifted the bacterial but not the
      archaeal community composition. After 3 months of incubation, only sediment
      slurries incubated with 10 mM (13) C-acetate showed detectable (13) C-DNA
      labeling. Based on 16S rRNA and dsrB gene PCR amplicon sequencing, the (13) C
      labeled DNA pool was dominated by a single type of sulfate reducer representing a
      novel genus in the family Desulfobacteraceae. In addition, members of the
      uncultivated Crenarchaeotal group C3 were enriched in the (13) C-labeled DNA. Our
      results were reproducible across biological replicate experiments and provide new
      information about the identities of uncultured acetate-consuming bacteria and
      archaea in marine sediments. 

PMID- 25950867
TI  - Sedentary Behavior and Physical Activity Patterns in Older Adults After Hip
      Fracture: A Call to Action.
AB  - OBJECTIVES: To characterize patterns of sedentary behavior and physical activity
      in older adults recovering from hip fracture and to determine characteristics
      associated with activity. METHODS: Community-dwelling, Canadian adults (65
      years+) who sustained hip fracture wore an accelerometer at the waist for seven
      days and provided information on quality of life, falls self-efficacy, cognitive
      functioning, and mobility. RESULTS: There were 53 older adults (mean age [SD]
      79.5 [7.8] years) enrolled in the study; 49 had valid data and demonstrated high
      levels of sedentary time (median [p10, p90] 591.3 [482.2, 707.2] minutes/day),
      low levels of light activity (186.6 [72.6, 293.7]), and MVPA (2 [0.1, 27.6]), as
      well as few daily steps (2467.7 [617.1, 6820.4]). Regression analyses showed that
      age, gender, gait speed, and time since fracture were associated with outcomes.
      CONCLUSIONS: Older adults have long periods of sedentary time with minimal
      activity. Results are a call to action to encourage people to sit less and move
      more.

PMID- 25950868
TI  - Phosphorylation of myofibrillar proteins in post-mortem ovine muscle with
      different tenderness.
AB  - BACKGROUND: Tenderness is one of the most important quality attributes especially
      for beef and lamb. As protein phosphorylation and dephosphorylation regulate
      glycolysis, muscle contraction and turnover of proteins within living cells, it
      may contribute to the conversion of muscle to meat. The changes of myofibrillar
      protein phosphorylation in post-mortem ovine muscle with different levels of
      tenderness were investigated in this study. RESULTS: The protein phosphorylation
      level (P/T ratio) of the tender group increased from 0.5 to 12 h post mortem and
      then decreased. The P/T ratio of tough group increased during 24 h post mortem,
      increasing faster from 0.5 to 4 h post mortem than from 4 to 24 h post mortem.The
      global phosphorylation level of tough meat was significantly higher than tender
      meat at 4, 12 and 24 h post mortem (P < 0.05). Protein identification revealed
      that most of the phosphoproteins were proteins with sarcomeric function; the
      others were involved in glycometabolism, stress response, etc. The
      phosphorylation levels of myofibrillar proteins, e.g. myosin light chain 2 and
      actin, were significantly different among groups of different tenderness and at
      different post-mortem time points (P < 0.05). CONCLUSION: Protein phosphorylation
      may influence meat rigor mortis through contractile machinery and glycolysis,
      which in turn affect meat tenderness.

PMID- 25950870
TI  - Iron-catalyzed C(sp(2))-H and C(sp(3))-H methylations of amides and anilides.
AB  - The so-called magic methyl effect significantly boosts the bioactivities and
      physical properties of pharmacologically active drugs. Direct introduction of the
      methyl group by C?H activation was accomplished with a versatile iron catalyst,
      which enabled the C?H methylation of (hetero)benzamides, anilides, alkenes, and
      even alkanes by triazole assistance in a chemo-, site- and diastereo-selective
      fashion. 

PMID- 25950869
TI  - Highly Amino Acid Selective Hydrolysis of Myoglobin at Aspartate Residues as
      Promoted by Zirconium(IV)-Substituted Polyoxometalates.
AB  - SDS-PAGE/Edman degradation and HPLC MS/MS showed that zirconium(IV)-substituted
      Lindqvist-, Keggin-, and Wells-Dawson-type polyoxometalates (POMs) selectively
      hydrolyze the protein myoglobin at Asp-X peptide bonds under mildly acidic and
      neutral conditions. This transformation is the first example of highly sequence
      selective protein hydrolysis by POMs, a novel class of protein-hydrolyzing
      agents. The selectivity is directed by Asp residues located on the surface of the
      protein and is further assisted by electrostatic interactions between the
      negatively charged POMs and positively charged surface patches in the vicinity of
      the cleavage site.

PMID- 25950871
TI  - Catalytic Asymmetric Synthesis of Phosphine Boronates.
AB  - The first catalytic enantioselective synthesis of ambiphilic phosphine boronate
      esters is presented. The asymmetric boration of alpha,beta-unsaturated phosphine
      oxides catalyzed by a copper bisphosphine complex affords optically active
      organoboronate esters that bear a vicinal phosphine oxide group in good yields
      and high enantiomeric excess. The synthetic utility of the products is
      demonstrated through stereospecific transformations into multifunctional
      optically active compounds. 

PMID- 25950872
TI  - National trends in rate of patients hospitalized for heart failure and heart
      failure mortality in France, 2000-2012.
AB  - AIMS: The objectives of this study were to describe annual trends in patients
      hospitalized for heart failure (HF) and HF-associated mortality rates in France
      between 2000 and 2012. METHODS AND RESULTS: Hospital discharge data were
      extracted from the French National Hospitalization Database (PMSI). Mortality
      data were obtained from the French National Mortality Database. HF events
      constituting the underlying or associated cause of death were selected. Rates
      were age standardized using the 2010 European census population as the standard
      population. Time trends were tested using a Poisson regression model. In 2012,
      the overall age-standardized rate of patients hospitalized for HF was 246.2 per
      100,000 inhabitants. The age-standardized rate of HF-associated mortality was
      113.8 per 100,000 inhabitants in 2010. Hospitalized patient rates remained steady
      between 2002 and 2012, whereas mortality decreased by 3.3% annually from 2000 to
      2010. Trends in hospitalized patients and mortality differed significantly
      between men and women, particularly among the 45- to 55- and 65- to 74-year-old
      age groups, with a smaller decrease observed in women. CONCLUSION: Among men, a
      slight decrease in patients hospitalized for HF and a substantial reduction in
      mortality were observed. Among women, only a large decrease in HF mortality was
      observed. HF remains one of the leading causes of death and hospitalization in
      France, particularly in the elderly.

PMID- 25950873
TI  - Suspected posaconazole toxicity in a pediatric oncology patient.

PMID- 25950874
TI  - Vaginal estrogen administration to prevent cervical os obliteration following
      cervical conization in women with amenorrhea.
AB  - BACKGROUND: Our goal was to evaluate the use of vaginal estrogen cream in
      preventing cervical os obliteration in postmenopausal patients undergoing
      cervical cone biopsies. MATERIALS AND METHODS: This study is a retrospective
      review of postmenopausal women who underwent cervical cone biopsies (laser or
      electrosurgical loop excision) in the author's practice. All patients were
      treated with 2 g of vaginal conjugated estrogen cream daily for 1 month following
      cone biopsy. The patients were seen 4 months later, and the cervix was evaluated.
      The percentage of women whose cervical os was patent, stenotic, or obliterated
      was compared to historical controls and, within this series, laser and
      electrosurgical loop excision groups were compared. RESULTS: Seventeen patients
      underwent conization (8 laser conizations, 9 electrosurgical loop excisions) and
      postcone treatment with estrogen cream. On average, the patients were 59.4 years
      old and 10.7 years postmenopausal. The follow-up interval ranged from 2 to 10
      months, with a mean of 4.4 months. In 10 patients, the cervix was patent, in 4 it
      was stenotic, and in 3 it was obliterated. The transformation zone was visualized
      fully in three patients before the cone biopsy and in three different patients
      after the cone biopsy. The outcome for patients treated with vaginal estrogen was
      significantly better (p < .013) than that for historical controls not treated
      with vaginal estrogen. However, the laser and electrosurgical loop excision
      groups differed significantly. Four of the eight laser patients had previous
      cervical treatment, compared with one of nine for electrosurgical loop excision.
      The laser group was not different from historical controls with regard to
      stenosis or obliteration, but the electrosurgical loop excision group had
      significantly less stenosis or obliteration than did either (p < .016). No trend
      could be identified regarding the length of the cone specimen between the laser
      and electrosurgical loop excision groups. All 5 patients with previous cervical
      procedures (but only 2 of 12 without previous procedures) developed stenosis or
      obliteration. CONCLUSIONS: Larger randomized control trials are needed to
      determine if vaginal estrogen cream is beneficial in preventing cervical os
      obliteration in postmenopausal patients undergoing conization procedures; to
      compare laser and electrosurgical loop excision; and to determine the effect of
      previous cervical procedures on the rate of cervical os obliteration in these
      groups of patients.

PMID- 25950875
TI  - Comparison of standard and loupe colposcopy (part I).
AB  - BACKGROUND: Our objective was to determine whether colposcopy can be performed
      with surgical-type loupes. METHODS: Sixty-one patients with abnormal Papanicolaou
      (Pap) smear test reports were examined with 6* loupes supplied by Designs For
      Vision, Inc. (Ronkonkoma, NY) and with a standard Zeiss Colposcope (Model OM-1).
      Comparisons between the two instruments were made for colposcopic impression and
      final histological analysis. Statistical analysis was performed by using the
      Kappa test. RESULTS: Comparison of the two methods of examination demonstrated
      excellent agreement (kappa = .86) with Pap smear and biopsy results. CONCLUSIONS:
      We decided that surgical loupes are adequate for colposcopic examination.

PMID- 25950876
TI  - Comparison of Standard and Loupe Colposcopy (Part II): Initial Experience with a
      New 6*-10* Surgical Loupe.
AB  - BACKGROUND: Our objective was to describe our experience in using a newly
      designed surgical loupe as a substitute device for colposcopy. METHODS: Eighty
      two patients were examined with a prototype surgical loupe. The instrument has a
      self-contained halogen light source, allows for 6* and 10* magnification, and has
      a green filter. Colposcopic impression within one degree of the histological
      diagnosis was considered in agreement. The colposcopic impression using the new
      instrument was compared to biopsy diagnoses. RESULTS: Colposcopic impressions
      with this new instrument agreed with final histological diagnoses in 93% of
      cases. The instrument was easy to use. CONCLUSION: The 6* to 10* surgical loupe
      is comfortable to use. Correlation with final pathological evaluation is
      comparable to standard colposcopic instruments. A trial of this instrument
      against a standard colposcope is ongoing.

PMID- 25950877
TI  - Training cytotechnologists to perform papanicolaou smear screening: development
      and testing of a third world program.
AB  - BACKGROUND: Our objective was (1) to develop a training program for teaching
      cytotechnology students how to perform Papanicolaou (Pap) smear collection, and
      (2) to compare the Pap smear adequacy rates of trained cytotechnicians to those
      of physicians screening the same population. METHODS: Cytotechnology students
      received formal lectures about collection and transport of Pap smears and
      clinical proctoring of Pap smear collection in at least 20 patients. Ten months
      after completion of training, a review of screening Pap smears collected by all
      health care professionals over 1 month was performed. Cytopathology review was
      performed in a blinded fashion. RESULTS: In November 1994, 1,411 screening Pap
      smears were performed. Patients were seen randomly by generalists, gynecologists,
      cytotechnicians, or oncologists with collection rates of 991 (70%), 221 (16%),
      100 (7%), and 99 (7%) Pap smears, respectively. Inadequate sampling rates (i.e.,
      less than 70% of the slide surface covered with a cell monolayer, endocervical
      cells present if uterus was in situ, and fewer than 25% of marker cells obscured
      by blood or inflammatory cells) were: generalists, 8.8%; gynecologists, 9.9%;
      cytotechnicians, 9.0%; and oncologists, 58.6%. No significant differences were
      seen in the inadequacy rates of the first three groups, though the oncologists
      were more likely to perform inadequate Pap smears (p < .01). CONCLUSIONS: Third
      World cytotechnicians can be taught the rudimentary aspects of Pap smear
      collection, with acceptable rates of inadequate sampling similar to their
      physician colleagues. Oncologist specialists either should be retrained in the
      proper collection and processing of Pap smears or should be excluded from this
      primary care activity.

PMID- 25950878
TI  - A comparison of loop electrosurgical excision, laser ablation, and cold-knife
      conization in relation to precise specimen removal in an inanimate model.
AB  - BACKGROUND: The purpose of this study is to compare loop electrosurgical
      excision, laser ablation, and coldknife conization for accuracy of excision in a
      model simulating the nulliparous uterine cervix. METHODS: Twenty obstetrics and
      gynecology residents excised or ablated specimens (n = 300) by using loop
      electrosurgical excision, laser, and scalpel. Preprepared specimens (bologna)
      were cut to simulate the adult, nulliparous cervix. These specimens were marked
      with templates to simulate cervical lesions. The accuracy of excision, time for
      excision, gender differences, and years in training were compared by using
      repeated measures from analysis of variance and t tests. RESULTS: Comparisons
      showed loop electrosurgical excision was more precise than was laser (F = 4.58;
      df = 1,15; p < .049) or cold-knife conization (F = 15.63; df = 1,15; p = .001).
      Laser ablation produced more specimens that were too shallow, and cold-knife
      conization resulted in specimens that were too deep. No differences were found
      among postgraduate years of training, but gender differences were revealed. Loop
      electrosurgical excision took significantly less time (mean = 23 seconds,
      standard deviation = 11.4 seconds) than laser ablation (mean = 135 seconds,
      standard deviation = 55.7 seconds; F = 68.22; df 1,15; p = .0001)) or coldknife
      excision (mean = 105 seconds; standard deviation = 37.9 seconds; F = 85.48; df =
      1,15; p = .0001). CONCLUSIONS: Using this model, loop electrosurgical excision is
      more precise and faster than laser ablation or cold- knife conization. Resident
      surgeons may be more precise in excising cervical lesions with this modality.

PMID- 25950879
TI  - Large-Loop Excision Using a New Probe: Variloop for the Treatment of CIN.
AB  - BACKGROUND: Our objective was to evaluate the efficiency of using a diathermic
      loop with an adjustable diameter (Variloop for the treatment of cervical
      intraepithelial neoplasia (CIN) in outpatient surgery. MATERIALS AND METHODS:
      Loop electrosurgical excision was performed on 185 patients, including 21 (11.3%)
      with low-grade lesions and an endocervical squamocolumnar junction, 44 (23.7%)
      with CIN2, 118 (63.7%) with CIN3, and 2 (1%) with discrepancies between
      cytological and histological findings. The procedure was performed in an average
      of 10 minutes. For 177 patients, local anesthetic was used. In all cases, the
      specimen was removed in one piece. RESULTS: We observed minimal epithelial
      distortion with mild coagulation necrosis at the edge of the specimens in 2 of
      185 (1%) cases, but this did not interfere with the histological evaluation.
      Correlation between the biopsy and the conization diagnosis was the best for
      CIN3, found in 70% of the cases. However, two cases of microinvasion and three
      cases of adenocarcinoma in situ that were diagnosed were not suspected
      preoperatively in any of these patients. In 171 of 185 cases (92.4%), there was
      no endocervical margin involvement. At the 1-year follow-up, two patients had a
      moderate stenosis with a squamocolumnar junction not visualized, and two others
      had a severe stenosis with a marked cervical narrowing. CONCLUSIONS: The use of
      the diathermic loop with adjustable diameter (Variloop) allows efficient
      treatment of CIN, wherein endocervical development does not exceed 15 mm from the
      external os without causing significant thermic alterations.

PMID- 25950880
TI  - Papanicolaou smears showing atypical glandular cells of undetermined
      significance: a case series.
AB  - BACKGROUND: The authors' objective was to determine retrospectively the methods
      used to follow up atypical glandular cells of undetermined significance (AGUS) on
      Papanicolaou smears and to evaluate the effectiveness of those methods. MATERIAL
      AND METHODS: The charts of all patients with AGUS smears obtained between
      February 1993 and April 1996 were reviewed retrospectively, and information was
      extracted. A computer database was used to identify the patients and review the
      method of evaluation. The findings from histological sampling also are reported
      and analyzed. All findings are reported descriptively. RESULTS: Seventy-nine AGUS
      smears were evaluated. Of these, it was found that six patients had no follow-up.
      Of the 62 with histological followup, most (74%) underwent colposcopy,
      endometrial biopsy (63%), or endocervical curettage (50%). Cervical or vaginal
      biopsy, cervical conization, hysteroscopy, and hysterectomy also were performed.
      Twenty-seven patients underwent more than one procedure for tissue sampling. Of
      the 62 patients from whom histological samples were taken, 18 (29%) were found to
      have clinically significant lesions, 11 of which were carcinomas. CONCLUSIONS: In
      our clinic, AGUS smears are a result of a significant number of high-grade
      neoplastic findings. Histological evaluation is necessary in most cases for
      accurate diagnosis because of the multiple, varied potential etiologies of AGUS
      smears.

PMID- 25950882
TI  - ASCCP Practice Guidelines: Management Issues Related to Quality of the Smear.

PMID- 25950881
TI  - The treatment of premalignant lesions of the uterine cervix.
AB  - BACKGROUND: Understanding the reasons for treatment of premalignant lesions of
      the cervix, as well as which lesions require therapy, is key to successful
      outcomes of therapy. Knowing the treatment modalities available and when to
      select each one is an essential part of proper patient care. When to observe and
      when to treat are critical decisions. CONCLUSIONS: Since the two basic approaches
      to treatment are either local destruction or excision, it is incumbent upon the
      treating physician to understand the values and complications attached to each
      method.

PMID- 25950883
TI  - Electrosurgical Excision Procedures: LLETZ and LEEP-A Critical Analysis.

PMID- 25950884
TI  - Home study course: spring 1997.
AB  - ? OBJECTIVE: : The Home Study Course is intended for the practicing colposcopist
      or practitioner who is seeking to develop or enhance his or her colposcopic
      skills. The goal of the course is to present colposcopic cases that are unusual
      or instructive in terms of appearance, presentation, or management, or that
      demonstrate new and important knowledge in the area of colposcopy or pathology.
      Participants may benefit from reading and studying the material or from testing
      their knowledge by answering the questions. ? ACCME ACCREDITATION: : The American
      Society for Colposcopy and Cervical Pathology (ASCCP) is accredited by the
      Accreditation Council for Continuing Medical Education (ACMME) to sponsor
      continuing medical education for physicians. The ASCCP designates this continuing
      medical education activity for 1 credit hour in Category I of the Physicians'
      Recognition Award of the American Medical Association. Credit is available for
      those who choose to apply.

PMID- 25950885
TI  - American society for colposcopy and cervical pathology.

PMID- 25950886
TI  - Review of current concepts of revascularization/revitalization.
AB  - This review focuses on the current concepts on revascularization/revitalization
      therapy. Revascularization/revitalization procedures performed under current
      protocols have reportedly achieved successful clinical and radiographical
      outcomes for immature permanent teeth with non-vital pulps; however, randomized
      prospective studies are needed to develop evidence-based methodologies for
      regenerative endodontic treatment. 

PMID- 25950887
TI  - Computer-based surgical planning and custom-made titanium implants for cranial
      fibrous dysplasia.
AB  - BACKGROUND: The procedure of reconstruction after the removal of cranial fibrous
      dysplasia (FD) must be precise to achieve good functional and aesthetic results.
      Intraoperative modeling of implants is difficult and may cause cosmetic
      disturbances. OBJECTIVE: To present our experience with the treatment of cranial
      FD using preoperative computer-based surgical planning of tumor removal with
      reconstruction of the cranium with custom-made titanium implants. METHODS: Four
      patients underwent surgical treatment for cranial FD over a 2-year period. All
      patients were male with a mean age of 25.25 years and had monostotic-type FD.
      Computed tomography (CT) with 0.5-mm slices was obtained preoperatively. Computer
      based planning of the tumor removal was performed, and a template was created by
      the computer to determine the margins of tumor removal. After this procedure, the
      preoperative computer-based construction of the titanium implant was performed.
      The patients underwent surgical treatment, and the tumor was removed with the use
      of this template. Then, the titanium implant was inserted onto the bone defect
      and fixed with mini-screws. Patients were followed up by periodic CT scans.
      RESULTS: The histological diagnosis of all patients was FD. No intraoperative or
      postoperative complications have occurred. Postoperative CT scans showed complete
      tumor removal and confirmed appropriate cosmetic reconstruction. The mean follow
      up period was 15.25 months. CONCLUSION: Computer-based surgical planning
      associated with the production of custom-made titanium implants is a highly
      promising method for the treatment of cranial FD. Better radiological and
      cosmetic outcomes could be obtained by this technique with interdisciplinary work
      with medical designers.

PMID- 25950888
TI  - Three-dimensional topographic fiber tract anatomy of the cerebrum.
AB  - BACKGROUND: The fiber tracts of the cerebrum may be a more important determinant
      of resection limits than the cortex. Better knowledge of the 3-dimensional (3-D)
      anatomic organization of the fiber pathways is important in planning safe and
      accurate surgery for lesions within the cerebrum. OBJECTIVE: To examine the
      topographic anatomy of fiber tracts and subcortical gray matter of the human
      cerebrum and their relationships with consistent cortical, ventricular, and
      nuclear landmarks. METHODS: Twenty-five formalin-fixed human brains and 4 whole
      cadaveric heads were examined by fiber dissection technique and *6 to *40
      magnification. The fiber tracts and central core structures, including the insula
      and basal ganglia, were examined and their relationships captured in 3-D
      photography. The depth between the surface of the cortical gyri and selected
      fiber tracts was measured. RESULTS: The topographic relationships of the
      important association, projection, and commissural fasciculi within the cerebrum
      and superficial cortical landmarks were identified. Important landmarks with
      consistent relationships to the fiber tracts were the cortical gyri and sulci,
      limiting sulci of the insula, nuclear masses in the central core, and lateral
      ventricles. The fiber tracts were also organized in a consistent pattern in
      relation to each other. The anatomic findings are briefly compared with
      functional data from clinicoradiological analysis and intraoperative stimulation
      of fiber tracts. CONCLUSION: An understanding of the 3-D anatomic organization of
      the fiber tracts of the brain is essential in planning safe and accurate cerebral
      surgery.

PMID- 25950889
TI  - Fluorescence-guided resection with 5-aminolevulinic Acid of subependymomas of the
      fourth ventricle: report of 2 cases: technical case report.
AB  - BACKGROUND AND IMPORTANCE: The usefulness of 5-aminolevulinic acid (5-ALA) for
      resection of malignant astrocytomas has been established in recent years. In
      addition to these tumors, it has been reported that 5-ALA fluorescence could be
      elicited in other tumors such as intracranial and spinal meningiomas or posterior
      fossa and spinal cord ependymomas, resulting in improved resections. Here, we
      present 2 cases of subependymomas of the fourth ventricle that showed intense
      fluorescence after 5-ALA administration. To the best of our knowledge, these are
      the first reported cases of subependymomas in this location in which 5-ALA
      elicited useful fluorescence. CLINICAL PRESENTATION: Case 1 was a 61-year-old
      woman with a history of headaches accompanied by vomiting in the last month.
      Magnetic resonance imaging (MRI) revealed a tumor occupying the fourth ventricle
      with slight irregular enhancement. She was operated on after administration of 5
      ALA. The tumor emitted intense red fluorescence when illuminated with blue light.
      An MRI performed 48 hours after surgery confirmed complete resection of the
      tumor. The pathological diagnosis was subependymoma. Case 2 was a 35-year-old man
      with a history of several months of headaches and vomiting. An MRI revealed a
      tumor occupying the caudal part of the fourth ventricle with moderate and
      irregular enhancement. He was operated on after administration of 5-ALA. The
      tumor showed intense fluorescence. An MRI performed 48 hours after surgery
      confirmed a complete resection of the tumor. The pathological diagnosis was
      subependymoma. CONCLUSION: Fluorescence-guided resection with 5-ALA may be useful
      for resection of subependymomas of the fourth ventricle. However, further studies
      are needed.

PMID- 25950890
TI  - A comparison of colposcopy using optical and video colposcopes.
AB  - OBJECTIVE: To compare the colposcopic adequacy, colposcopic impressions,
      histologic sampling intent, biopsy site location, procedural complications, and
      difficulty of colposcopic examinations using optical and video colposcopes.
      MATERIALS AND METHODS: Women and men presenting consecutively for colposcopy were
      examined independently by two colposcopists using alternately either an optical
      or video colposcope. Colposcopists individually recorded their exam adequacy,
      colposcopic impression, biopsy intent and site, procedural complications, and
      difficulty of examination. Most colposcopists had no prior experience with video
      colposcopes. RESULTS: Of 300 patients, mean age 35.3 years (+/-12.2 SD),
      examined, 29.7% were nulliparous, 4.9% pregnant, 52.5% had a previous biopsy and
      34.3% had prior cervical treatment. Agreement between colposcopes was excellent
      for visualizing the complete squamocolumnar junction (75.6%, x = 6.40, p = 0.09).
      Colposcopists using the video colposcope had more unsatisfactory exams of the
      endocervical canal (36.6%, 97/265) than did colposcopists using optical
      colposcopes (24.9%, 66/265, x = 16.65, p = 0.001). Colposcopic impression
      agreement with pathology results were not significantly different between the
      video (58.1%) and optical (57.0%) colposcopes (x = 0.09, p = 0.8). Biopsy intent
      (79.9% agreement, x = 0.20, p = 0.7) and biopsy site selection by cervical
      quadrant were not significantly different for the two colposcopes. Both types of
      colposcopes were rated extremely easy to use, but colposcopy in general (T =
      3.97, p < 0.001), visualization (T = 2.98, p = 0.002), assessment (T = 2.76, p =
      0.004), and sampling (Wilcoxon = 2.27, p = 0.02) were determined to be easier
      when using optical colposcopes. CONCLUSIONS: Video colposcopes have similar,
      clinically relevant outcomes when compared with optical colposcopes.
      Colposcopists using optical colposcopes reported easier colposcopy exams and
      fewer unsatisfactory examinations of the endocervical canal. These findings may
      represent a learning curve effect as colposcopists become familiar with operating
      the video colposcope.?.

PMID- 25950891
TI  - Double-LEEP Cone Procedure as an Alternative to Cold-Knife Conization in
      Management of Cervical Intraepithelial Neoplasia.
AB  - OBJECTIVES: To compare the double-LEEP cone procedure with cold-knife conization
      to treat cervical intraepithelial neoplasia; to evaluate the specimen adequacy
      regarding resection margins and residual disease. METHODS AND MATERIALS: Of 137
      patients with cervical intraepithelial neoplasia, 60 patients had cold-knife cone
      and 77 had double-LEEP cone procedure. The indications were the same for both
      groups. The average follow-up time was 6 months. RESULTS: Therapeutic failure
      (incomplete excision) rate was 14% for double-LEEP cone procedure and 13% for
      cold-knife conization (p = 0.87). Recurrent cervical intraepithelial neoplasia
      rate was 16% for double-LEEP cone procedure and 7% for cold-knife conization (p =
      0.44) at 6 months. Rates of bleeding complication were 2.6% for double-LEEP cone
      procedure and 3.3% for cold-knife conization (p = 0.80). These figures were not
      statistically significant. Thermal artifact was 10% of double-LEEP cone procedure
      specimens with only one with severe thermal damage preventing accurate grading of
      cervical intraepithelial neoplasia. CONCLUSION: There was no significant
      difference between double-LEEP cone procedure (86%) and cold-knife conization
      (87%) (p = 0.8). It appears that double LEEP performed as an outpatient procedure
      can be an acceptable alternative to cold-knife conization in patients with
      cervical intraepithelial neoplasia.?.

PMID- 25950892
TI  - Comparing endocervical curettage and endocervical brush at colposcopy.
AB  - OBJECTIVE: To determine the sensitivity and specificity of the cytologic
      diagnosis obtained from the endocervical brushings (ECB) compared to the
      histologic information obtained from endocervical curettage (ECC). MATERIALS AND
      METHODS: Of 369 patients referred for colposcopy, 105 nonpregnant women underwent
      conization and/or hysterectomy allowing analysis of tissue samples. The racially
      diverse, sociodemographically homogeneous population was 15 through 71 years old.
      Participants had repeat Papnicolaou smears, ECB, colposcopy (with/without
      directed biopsy), and ECC. The sensitivity, specificity, and positive and
      negative predictive values of ECB and ECC for diagnosing endocervical disease
      were compared. RESULTS: No invasive cancers were missed by either ECB or ECC. The
      sensitivity of ECB was 93%, which exceeded that of ECC (62%) for detection of
      endocervical pathology. However, the negative predictive value of both ECB and
      ECC was excellent. The specificity of ECC (63%) exceeded that of ECB (25%) for
      detection of endocervical pathology. However, the positive predictive value of
      both ECC and ECB was poor. CONCLUSION: This study suggests that ECB can replace
      ECC during colposcopic evaluation of an abnormal Papnicolaou smear.?.

PMID- 25950893
TI  - Home study course: spring 2000.
AB  - ? OBJECTIVE: : The Home Study Course is intended for the practicing colposcopist
      or practitioner who is seeking to develop or enhance his or her colposcopic
      skills. The goal of the course is to present colposcopic cases that are unusual
      or instructive in terms of appearance, presentation, or management, or that
      demonstrate new and important knowledge in the area of colposcopy or pathology.
      Participants may benefit from reading and studying the material or from testing
      their knowledge by answering the questions. ? ACCME ACCREDITATION: : The American
      Society for Colposcopy and Cervical Pathology (ASCCP) is accredited by the
      Accreditation Council for Continuing Medical Education (ACCME) to sponsor
      continuing medical education for physicians. The ASCCP designates this continuing
      medical education activity for 1 Credit hour in Category 1 of the Physician's
      Recognition Award of the American Medical Association. Credit is available for
      those who choose to apply. The Home Study Course is planned and produced in
      accordance with the ACCME's Essential Areas and Elements.

PMID- 25950894
TI  - ASCCP Practice Guidelines Management Guidelines for the Follow-up of Cytology
      Read as Low Grade Squamous Intraepithelial Lesion.

PMID- 25950895
TI  - ASCCP Practice Guidelines Management Guidelines for the Follow-up of Cytology
      Interpreted as Benign Cellular Changes on Papanicolaou Smear of the Cervix or
      Vagina.

PMID- 25950896
TI  - ASCCP Practice Guidelines Management Guidelines for the Follow-up of Atypical
      Squamous Cells of Undetermined Significance (ASCUS).
AB  - : Editor's Note: This guideline was first published in The Colposcopist in
      January 1996 and reflected the peer-reviewed literature available on the
      management of ASCUS at that time. The decision to republish this guideline in The
      Journal of Lower Genital Tract Disease, to accompany guidelines on the management
      of low-grade squamous intraepithelial lesion (LGSIL) and benign cellular changes
      (BCC) was made to complete the set of guidelines in the Journal pertaining to
      management of the cytology screening system. (See also previous guidelines on
      Management Issues Related to the Quality of the Smear, Management of Atypical
      Glandular Cells of Undetermined Significance (AGUS), and the Abnormal Pap Follow
      up System.) Our original intention was to update the ASCUS guideline for this
      publication in the expectation that the data from the enrollment phase of the
      National Cancer Institute's ASCUS LGSIL Triage Study (ALTS) would be available to
      provide relevant evidence-based recommendations. The unavailability of this data
      at this time has ensured a later update of the ASCUS guideline. However, an
      accumulating body of new literature, particularly on the clinical utility of HPV
      testing with Hybrid Capture II (Digene Corp., Gaithersburg, MD), will be
      incorporated within the next year with the enrollment ALTS data in a new ASCUS
      guideline. Until that time, the guideline presented here remains the
      recommendation of the ASCCP, based on the review of the literature at that time,
      and on the collective experience and knowledge of the ASCCP Practice Committee
      and the Board of Directors.The cost analysis in this guideline is based upon a
      set of cost assumptions which will vary from setting to setting. This analysis is
      intended to serve as a reference for average costs in a fee-for-service setting.
      The individual practitioner will need to analyze cost differentials for his/her
      own setting.This guideline reflects emerging clinical and scientific advances as
      of February 1996, and is subject to change. The information should not be
      construed as dictating an exclusive course of treatment or procedure to be
      followed. 

PMID- 25950897
TI  - The american society for colposcopy and cervical pathology: hagerstown, MD.

PMID- 25950898
TI  - Role of HPV Testing in Secondary and Primary Screening of Cervical Neoplasia.
AB  - OBJECTIVE: To evaluate the performance of HPV testing in identifying cervical
      neoplasia. MATERIALS AND METHODS: Minor cytologic atypia of the uterine cervix,
      particularly atypical squamous cells of undetermined significance (ASCUS)
      represent a vast group, at least three times more frequent than cytologic high
      grade squamous intraepithelial lesions (HGSIL). Even though, individually, ASCUS
      smears correspond to a normal cervix in nearly 80% of cases, their marked
      prevalence in the screened population suggests that this category of smear is one
      of the main sources of histologically confirmed high-grade SIL.The recent
      recommendations by the National Agency of Accreditation and Evaluation (ANAES)
      for managing ASCUS smears indicate that it is possible to advise a follow-up
      smear at regular intervals or immediate colposcopy. The follow-up smear option
      has limitations related to its incomplete sensitivity (25-40% of existing high
      grade SIL can go unrecognized). Colposcopy has optimal sensitivity in recognizing
      high-grade lesions, but falls short due to lack of specificity.The Hybrid Capture
      (HC II) (Digene, Silver Spring, MD) test is an objective and reproducible test
      that makes it possible to detect nononcogenic and oncogenic types of human
      papillomavirus (HPV) and the DNA viral load, thereby increasing the probability
      that significant cervical lesions will not go unrecognized. RESULTS: The Hybrid
      Capture test is simple to perform and positive results for high-risk HPV strongly
      correlate with the presence of high-grade CIN (sensitivity of approximately 98%).
      The test's nearly 100% negative predictive value makes it possibly to fully
      reassure patients who have had an ASCUS smear, freeing them from regular
      cytologic follow-up, colposcopy, and biopsy. A Hybrid Capture II test that is
      positive for oncogenic HPV significantly increases the probability of recognizing
      significant, precancerous cervical lesions. When the reference smear has been
      done in a liquid suspension, the Hybrid Capture test can be done on the residual
      cells in the suspension, thereby avoiding an additional visit. CONCLUSION: Recent
      French and international evaluations and publications should encourage the ANAES
      task force to propose the HPV test as a possible option for managing smears with
      minor atypia.?.

PMID- 25950899
TI  - Differential use of autophagy by primary dendritic cells specialized in cross
      presentation.
AB  - Antigen-presenting cells survey their environment and present captured antigens
      bound to major histocompatibility complex (MHC) molecules. Formation of MHC
      antigen complexes occurs in specialized compartments where multiple protein
      trafficking routes, still incompletely understood, converge. Autophagy is a route
      that enables the presentation of cytosolic antigen by MHC class II molecules.
      Some reports also implicate autophagy in the presentation of extracellular,
      endocytosed antigen by MHC class I molecules, a pathway termed "cross
      presentation." The role of autophagy in cross-presentation is controversial. This
      may be due to studies using different types of antigen presenting cells for which
      the use of autophagy is not well defined. Here we report that active use of
      autophagy is evident only in DC subtypes specialized in cross-presentation.
      However, the contribution of autophagy to cross-presentation varied depending on
      the form of antigen: it was negligible in the case of cell-associated antigen or
      antigen delivered via receptor-mediated endocytosis, but more prominent when the
      antigen was a soluble protein. These findings highlight the differential use of
      autophagy and its machinery by primary cells equipped with specific immune
      function, and prompt careful reassessment of the participation of this endocytic
      pathway in antigen cross-presentation. 

PMID- 25950901
TI  - Anetoderma arising in Reed syndrome: a case report and review of the literature.
AB  - Anetoderma is a cutaneous disorder characterized by loss of dermal elastic tissue
      resulting in papules from herniation of subcutaneous tissue or circumscribed
      areas of atrophic, wrinkled skin. Familial leiomyomatosis cutis et uteri (Reed
      syndrome) is an autosomal dominant disorder characterized by cutaneous and
      uterine leiomyomas. We report a 23-year-old male with Reed syndrome who presented
      with asymptomatic pearly white, atrophic, flaccid papules on the upper back and
      shoulder that depressed when palpated. Pathologic examination showed an
      unremarkable epidermis and central loss of dermal elastin, bordered by clumped
      elastin, as revealed with an elastin stain. The correlation of clinical and
      pathologic findings indicated a diagnosis of anetoderma arising in a patient with
      Reed syndrome. 

PMID- 25950900
TI  - Multilocus microsatellite typing of Leishmania and clinical applications: a
      review.
AB  - Microsatellite markers have been used for Leishmania genetic studies worldwide,
      giving useful insight into leishmaniasis epidemiology. Understanding the
      geographic distribution, dynamics of Leishmania populations, and disease
      epidemiology improved markedly with this tool. In endemic foci, the origins of
      antimony-resistant strains and multidrug treatment failures were explored with
      multilocus microsatellite typing (MLMT). High genetic variability was detected
      but no association between parasite genotypes and drug resistance was
      established. An association between MLMT profiles and clinical disease
      manifestations was highlighted in only three studies and this data needs further
      confirmation. At the individual level, MLMT provided information on relapse and
      reinfection when multiple leishmaniasis episodes occurred. This information could
      improve knowledge of epidemiology and guide therapeutic choices for active
      chronic visceral leishmaniasis, the disease form in some HIV-positive patients. 

PMID- 25950902
TI  - Lower urinary tract symptoms of prostate cancer patients undergoing treatments
      over eight-month follow-up.
AB  - AIMS AND OBJECTIVES: To examine the changes in lower urinary tract symptoms after
      open radical prostatectomy, laparoscopic radical prostatectomy and brachytherapy
      and to determine which treatment resulted in improved lower urinary tract
      symptoms at 8 months follow-up. BACKGROUND: Lower urinary tract symptoms are a
      primary side effect after prostate cancer treatment. DESIGN: A time-series survey
      design with descriptive and comparative elements. METHODS: A sample of 51
      prostate cancer patients was recruited: open radical prostatectomy = 20,
      laparoscopic radical prostatectomy = 23 and brachytherapy = 8. Data were
      collected at six time points: before treatment/baseline, 1 week post-treatment, 1
      month post-treatment, 2 month post-treatment, 3 month post-treatment and 8 months
      post-treatment. The lower urinary tract symptoms were assessed using the
      International Prostate Symptom Score, with a higher score indicating a worse
      condition. One-way anova was used to predict the progress of urinary symptoms
      after treatments. Bootstrap re-sampling was conducted to assess the stability of
      the outcomes. RESULTS: Although there were no significant differences in the
      lower urinary tract symptoms among the three groups after treatments, the
      laparoscopic radical prostatectomy group had the lowest International Prostate
      Symptom Score score at baseline. Compared with the baseline symptoms for patients
      undergoing each treatment, there were significant improvements after 2 months in
      the open radical prostatectomy and brachytherapy groups, and after 3 months in
      the laparoscopic radical prostatectomy group. CONCLUSIONS: The prostate cancer
      patients undergoing the three treatments have similar lower urinary tract
      symptoms over 8-month follow-up although different lower urinary tract symptoms
      were presented before treatments. RELEVANCE TO CLINICAL PRACTICE: Results could
      be applied to educating and counselling prostate cancer patients regarding
      symptoms during recovery after surgery. It could also help patients better
      understand the outcomes related to the differing treatment methods.

PMID- 25950903
TI  - Evidence for a KATP Channel in Rough Endoplasmic Reticulum (rerKATP Channel) of
      Rat Hepatocytes.
AB  - We report in a previous study the presence of a large conductance K+ channel in
      the membrane of rough endoplasmic reticulum (RER) from rat hepatocytes
      incorporated into lipid bilayers. Channel activity in this case was found to
      decrease in presence of ATP 100 uM on the cytoplasmic side and was totally
      inhibited at ATP concentrations greater than 0.25 mM. Although such features
      would be compatible with the presence of a KATP channel in the RER, recent data
      obtained from a brain mitochondrial inner membrane preparation have provided
      evidence for a Maxi-K channel which could also be blocked by ATP within the mM
      concentration range. A series of channel incorporation experiments was thus
      undertaken to determine if the ATP-sensitive channel originally observed in the
      RER corresponds to KATP channel. Our results indicate that the gating and
      permeation properties of this channel are unaffected by the addition of 800 nM
      charybdotoxin and 1 uM iberiotoxin, but appeared sensitive to 10 mM TEA and 2.5
      mM ATP. Furthermore, adding 100 uM glibenclamide at positive potentials and 400
      uM tolbutamide at negative or positive voltages caused a strong inhibition of
      channel activity. Finally Western blot analyses provided evidence for Kir6.2,
      SUR1 and/or SUR2B, and SUR2A expression in our RER fractions. It was concluded on
      the basis of these observations that the channel previously characterized in RER
      membranes corresponds to KATP, suggesting that opening of this channel may
      enhance Ca2+ releases, alter the dynamics of the Ca2+ transient and prevent
      accumulation of Ca2+ in the ER during Ca2+ overload. 

PMID- 25950904
TI  - Female rule in lemurs is ancestral and hormonally mediated.
AB  - Female social dominance (FSD) over males is unusual in mammals, yet characterizes
      most Malagasy lemurs, which represent almost 30% of all primates. Despite its
      prevalence in this suborder, both the evolutionary trajectory and proximate
      mechanism of FSD remain unclear. Potentially associated with FSD is a suite of
      behavioural, physiological and morphological traits in females that implicates
      (as a putative mechanism) 'masculinization' via androgen exposure; however,
      relative to conspecific males, female lemurs curiously show little evidence of
      raised androgen concentrations. By observing mixed-sex pairs of related Eulemur
      species, we identified two key study groups--one comprised of species expressing
      FSD and increased female scent marking, the other comprised of species (from a
      recently evolved clade) showing equal status between the sexes and the more
      traditional pattern of sexually dimorphic behaviour. Comparing females from these
      two groups, we show that FSD is associated with more masculine androgen profiles.
      Based on the widespread prevalence of male-like features in female lemurs and a
      current phylogeny, we suggest that relaxation of hormonally mediated FSD emerged
      only recently and that female masculinization may be the ancestral lemur
      condition, an idea that could revolutionize our understanding of the ancient
      socioecology and evolution of primate social systems.

PMID- 25950905
TI  - Combined 17beta-Estradiol with TCDD Promotes M2 Polarization of Macrophages in
      the Endometriotic Milieu with Aid of the Interaction between Endometrial Stromal
      Cells and Macrophages.
AB  - The goal of this study is to elucidate the effects of 17beta-estradiol and TCDD
      (2,3,7,8-tetrachlorodibenzo-p-dioxin) on macrophage phenotypes in the
      endometriotic milieu. Co-culture of endometrial stromal cells (ESCs) and U937
      cells (macrophage cell line) was performed to simulate the endometriotic milieu
      and to determine the effects of 17beta-estradiol and/or TCDD on IL10, IL12
      production and HLA-DR, CD86 expression by U937 macrophages. We found that
      combining 17beta-estradiol with TCDD has a synergistic effect on inducing M2
      activation when macrophages are co-cultured with ESCs. Moreover, the combination
      of 17beta-estradiol and TCDD significantly enhanced STAT3 and P38 phosphorylation
      in macrophages. Differentiation of M2 macrophages induced by 17beta-estradiol and
      TCDD were effectively abrogated by STAT3 and P38MAPK inhibitors, but not by
      ERK1/2 and JNK inhibitors. In conclusion, 17beta-estradiol and TCDD in the
      ectopic milieu may lead to the development of endometriosis by inducing M2
      polarization of macrophages through activation of the STAT3 and P38MAPK pathways.

PMID- 25950906
TI  - An Exploratory Study of HIV Risk Behaviors and Testing among Male Sex Workers in
      Beirut, Lebanon.
AB  - Male sex workers (MSW) are a particularly high-risk subset of men who have sex
      with men in Lebanon and report higher numbers of sex partners and lower rates of
      condom use. The purpose was to explore the factors influencing sexual risk
      behaviors and HIV testing among MSW. Qualitative interviews were conducted with
      16 MSW living in Beirut and working in bathhouses (hammam) or as escorts; content
      analysis identified emergent themes. Escorts reported more consistent condom use
      with clients and HIV testing than hammam MSW, with influential factors including
      HIV risk knowledge and perceived risk susceptibility, job security, and
      internalized stigma and related feelings of self-worth and fatalism regarding
      health and HIV risk. In contrast, both groups of MSW typically opted not to
      condoms with nonclient sex partners, in an effort to differentiate sex for work
      versus pleasure. The uptake of HIV testing was limited by concerns about the
      confidentiality of the test results and fear of repercussions of a positive test
      result for their health and employment. The respondents described an insular
      existence within the sex work culture, in part to limit exposure to stigma, which
      has implications for access to support as well as the influence of peer norms
      regarding sexual risk behavior and health seeking behaviors such as HIV testing.
      Further research is needed to tailor prevention and HIV testing efforts to
      reflect the distinct sexual health "cultures" that distinguish these two
      populations of MSW in Lebanon. 

PMID- 25950907
TI  - Drug use, hepatitis C, and service availability: perspectives of incarcerated
      rural women.
AB  - This study examined drug use, hepatitis C, and service availability and use among
      a high-risk sample of rural women serving time in jails. Data was collected from
      female offenders (N = 22) who participated in four focus groups in three rural
      jail facilities located in Appalachia. Findings indicated that drug misuse is
      prevalent in this impoverished area of the country, and that the primary route of
      administration of drug use is injection. Findings also indicate that injection
      drug use is also commonly associated with contracting hepatitis C (HCV), which is
      also perceived to be prevalent in the area. Despite knowledge associated with HCV
      risks, women in this sample were seemingly apathetic about the increasing spread
      of HCV in the area and unconcerned about the long-term consequences of the course
      of the infection. Implications for future research and practice are discussed.

PMID- 25950908
TI  - A novel and rapid method for obtaining high titre intact prion strains from
      mammalian brain.
AB  - Mammalian prions exist as multiple strains which produce characteristic and
      highly reproducible phenotypes in defined hosts. How this strain diversity is
      encoded by a protein-only agent remains one of the most interesting and
      challenging questions in biology with wide relevance to understanding other
      diseases involving the aggregation or polymerisation of misfolded host proteins.
      Progress in understanding mammalian prion strains has however been severely
      limited by the complexity and variability of the methods used for their isolation
      from infected tissue and no high resolution structures have yet been reported.
      Using high-throughput cell-based prion bioassay to re-examine prion purification
      from first principles we now report the isolation of prion strains to exceptional
      levels of purity from small quantities of infected brain and demonstrate faithful
      retention of biological and biochemical strain properties. The method's
      effectiveness and simplicity should facilitate its wide application and expedite
      structural studies of prions. 

PMID- 25950909
TI  - Somatic Mutations of FOXE1 in Papillary Thyroid Cancer.
AB  - BACKGROUND: Population-based studies have demonstrated an association of single
      nucleotide polymorphisms close to the thyroid transcription factor forkhead box
      E1 (FOXE1) gene with thyroid cancer. The dysregulation of forkhead proteins is
      increasingly recognized to play a role in the development and progression of
      cancer. The objective of the study was to seek to identify novel mutations in
      FOXE1 in papillary thyroid cancer (PTC) and to assess the effect of these
      mutations on protein expression and transcriptional function on FOXE1 responsive
      promoters. METHODS: The study was conducted at two tertiary referral hospitals.
      The coding region of FOXE1 was sequenced in tissue-derived DNA or RNA from 120
      patients with PTC and 110 patients with multinodular goiter (MNG). In vitro
      studies were performed to examine the protein expression and transcriptional
      function of FOXE1 mutants. A molecular model of the forkhead domain (FHD) of
      FOXE1 was generated using the SWISS-MODEL online server with the three
      dimensional structure of FOXD3 as a template. RESULTS: Three somatic missense
      mutations were detected in PTC resulting in the amino acid substitutions P54Q,
      K95Q, and L112F. One additional mutation was detected in a MNG (G140R). In vitro
      studies demonstrated marked impairment in transcriptional activation by all four
      FOXE1 mutants, which was not explained by differences in protein expression.
      Molecular modeling localized three of the mutations to highly conserved regions
      of the FHD. CONCLUSIONS: We have identified novel somatic mutations of FOXE1 in
      PTC. Mutational inactivation of FOXE1 is an uncommon event in thyroid tumors but
      may contribute to thyroid carcinogenesis and dedifferentiation in concert with
      other oncogenic drivers.

PMID- 25950910
TI  - Genetically predicted testosterone and systemic inflammation in men: a separate
      sample Mendelian randomization analysis in older Chinese men.
AB  - OBJECTIVES: Observationally, testosterone is negatively associated with systemic
      inflammation, but this association is open to both residual confounding and
      reverse causality. Large-scale randomized controlled trials (RCTs), assessing
      exogenous effects, are presently unavailable. We examined the association of
      endogenous testosterone with well-established systemic inflammatory markers
      (white blood cell, granulocyte, lymphocyte and high-sensitivity C-reactive
      protein (hsCRP)) using a separate-sample Mendelian randomization analysis to
      minimize reverse causality. METHODS: A genetic prediction rule for serum
      testosterone was developed in 289 young Chinese men with mean age of 21.0, using
      selected testosterone-related SNPs (rs10046, rs1008805 and rs1256031).
      Multivariable linear regression was used to examine the association of
      genetically predicted serum testosterone with inflammatory markers among 4,212
      older Chinese men from the Guangzhou Biobank Cohort Study. RESULTS: Genetically
      predicted testosterone was unrelated to white blood cell count (-0.01 109/L per
      nmol/L testosterone, 95% confidence interval (CI) -0.05 to 0.04), granulocyte
      count (-0.02 109/L, 95% CI -0.06 to 0.02), lymphocyte count (0.005 109/L, 95% CI 
      0.01 to 0.02) and hsCRP (-0.05 mg/L, 95% CI -0.15 to 0.06). CONCLUSION: Our
      findings did not corroborate any anti-inflammatory effects of testosterone or
      corresponding potentially protective effects of testosterone on chronic diseases
      resulting from reduced low-grade systemic inflammation.

PMID- 25950911
TI  - Development of Recombinant Adeno-Associated Virus Serotype 2/8 Carrying Kringle
      Domains of Human Plasminogen for Sustained Expression and Cancer Therapy.
AB  - Angiostatin and other plasminogen derivatives exhibit antitumor activities
      directly or indirectly, have demonstrated promising anticancer effects in
      preclinical studies, but have mostly failed in clinical trials partly due to
      their short serum half-lives. Our previous studies demonstrated that recombinant
      human plasminogen kringle 1-5 (K1-5) has superior antitumor activity compared
      with angiostatin. In addition, optimization of recombinant K1-5 with three amino
      acid substitutions enhances its antitumor effect. The current study was thus
      undertaken to evaluate prolonged expression of optimized K1-5 as cancer gene
      therapy. The recombinant adeno-associated virus (AAV) vector was used to express
      a secreted form of the optimized K1-5 (AAV-sK15tm) to improve its pharmacokinetic
      profile, which was considered to be the hurdle in angiostatin treatment of
      cancer. We successfully generated high-titer recombinant AAV vectors and observed
      sustained transgene expression for 567 days after a single injection of virus.
      The treated animals did not display any visible signs of abnormalities and showed
      normal serum biochemistry. The therapeutic potential of this treatment modality
      was demonstrated by both a strong inhibition of lung metastasis in the mouse
      B16F10 melanoma model and significant growth retardation of Lewis lung carcinoma
      xenografts in C57BL/6N mice as well as human A2058 melanoma xenografts in
      NOD/SCID (nonobese diabetic/severe combined immunodeficient) mice. Taken
      together, our results suggested that AAV-sK15tm produced long-term suppressive
      effects on cancer growth in vivo and should warrant serious consideration for
      clinical development. 

PMID- 25950912
TI  - Club Drugs and HIV/STD Infection: An Exploratory Analysis among Men Who Have Sex
      with Men in Changsha, China.
AB  - OBJECTIVE: To evaluate current club drug use and its potential association with
      the transmission of HIV/STD among Changsha men who have sex with men (MSM).
      METHOD: A cross-sectional survey was conducted by using self-administered
      questionnaires including information regarding socio-demographics, club drug use,
      high-risk behaviors, and HIV/STD infections. Multiple methods including venue
      based, peer referral using "snowball" techniques, and internet advertisements
      were used to recruit study participants. RESULTS: Of the 826 participants, 177
      (21.4%) reported that they had used club drugs at some time before or during sex
      in the past six months. MSM with young age, low education level, and seeking
      partners through the internet or bars were the main population who used drugs.
      Poppers were the most common drug used among Changsha MSM. The prevalence of HIV,
      syphilis, and herpes simplex virus-2 were higher among drug users. There were no
      significant differences in unprotected sexual intercourse and condom use between
      drug users and non-users. Compared with non-users, risk behaviors such as group
      sex, multiple sex partners, and sex with foreigners were more frequent among drug
      users. CONCLUSION: Club drug use is common among Changsha MSM, and is related to
      unsafe sex activities and HIV/STD infection. It is necessary to build novel
      targeted HIV prevention strategies to monitor and reduce club drug use among MSM.

PMID- 25950913
TI  - A post-developmental genetic screen for zebrafish models of inherited liver
      disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of
      chronic liver disease such as simple steatosis, nonalcoholic steatohepatitis
      (NASH), cirrhosis and fibrosis. However, the molecular pathogenesis and genetic
      variations causing NAFLD are poorly understood. The high prevalence and incidence
      of NAFLD suggests that genetic variations on a large number of genes might be
      involved in NAFLD. To identify genetic variants causing inherited liver disease,
      we used zebrafish as a model system for a large-scale mutant screen, and adopted
      a whole genome sequencing approach for rapid identification of mutated genes
      found in our screen. Here, we report on a forward genetic screen of ENU
      mutagenized zebrafish. From 250 F2 lines of ENU mutagenized zebrafish during post
      developmental stages (5 to 8 days post fertilization), we identified 19 unique
      mutant zebrafish lines displaying visual evidence of hepatomegaly and/or
      steatosis with no developmental defects. Histological analysis of mutants
      revealed several specific phenotypes, including common steatosis,
      micro/macrovesicular steatosis, hepatomegaly, ballooning, and acute
      hepatocellular necrosis. This work has identified multiple post-developmental
      mutants and establishes zebrafish as a novel animal model for post-developmental
      inherited liver disease. 

PMID- 25950914
TI  - Discovery of a high affinity and selective pyridine analog as a potential
      positron emission tomography imaging agent for cannabinoid type 2 receptor.
AB  - As part of our efforts to develop CB2 PET imaging agents, we investigated 2,5,6
      substituted pyridines as a novel class of potential CB2 PET ligands. A total of
      21 novel compounds were designed, synthesized, and evaluated for their potency
      and binding properties toward human and rodent CB1 and CB2. The most promising
      ligand 6a was radiolabeled with carbon-11 to yield 16 ([(11)C]RSR-056). Specific
      binding of 16 to CB2-positive spleen tissue of rats and mice was demonstrated by
      in vitro autogadiography and verified in vivo in PET and biodistribution
      experiments. Furthermore, 16 was evaluated in a lipopolysaccharid (LPS) induced
      murine model of neuroinflammation. Brain radioactivity was strikingly higher in
      the LPS-treated mice than the control mice. Compound 16 is a promising
      radiotracer for imaging CB2 in rodents. It might serve as a tool for the
      investigation of CB2 receptor expression levels in healthy tissues and different
      neuroinflammatory disorders in humans. 

PMID- 25950915
TI  - Prediction of novel alloy phases of Al with Sc or Ta.
AB  - Using the evolutionary optimization algorithm, as implemented in the USPEX
      crystal predictor program, and first principles total energy calculations, the
      compositional phase diagrams for Al-Sc and Al-Ta alloy systems at zero
      temperature and pressure have been calculated. In addition to the known binary
      intermetallic phases, new potentially stable alloys, AlSc3 and AlTa7, have been
      identified in the Al-poor region of the phase diagram. The dynamic and thermal
      stability of their lattices has been confirmed from the calculated vibrational
      normal mode spectra in the harmonic approximation. 

PMID- 25950916
TI  - Risk and protective factors for internalizing and externalizing outcomes among
      HIV-affected youth in Haiti.
AB  - The present study aims to: (1) estimate the levels of internalizing symptoms and
      externalizing behaviors among youth affected by HIV in central Haiti; and (2)
      examine the risk and protective factors associated with these outcomes to
      identify potential areas of intervention for HIV-affected youth. Baseline data
      for 492 youth affected by HIV (ages 10-17) and their 330 caregivers were
      collected for a pilot study of a psychosocial support intervention. Participants
      were recruited from a list of HIV-positive patients receiving care at Partners In
      Health/Zanmi Lasante clinic sites. Internalizing and externalizing behaviors were
      assessed using the Strengths and Difficulties Questionnaire. Demographic,
      economic, and social indicators were collected using a structured questionnaire
      administered by trained social workers. Youth affected by HIV in central Haiti
      displayed high levels of internalizing and, to a lesser degree, externalizing
      symptoms. Multivariate regression analysis demonstrated risk factors most
      strongly associated with internalizing symptoms (socioeconomic status, parental
      depressive symptoms) and externalizing behaviors (household living arrangements,
      such as living with a stepparent). Social support had a protective effect on
      externalizing behaviors for both caregiver (beta=-0.03, p=0.01) and self-report
      (beta=-0.05, p<0.0001). High levels of psychological distress were observed in
      this population, especially with respect to internalizing outcomes. Interventions
      should address the economic security, mental health, and access to antiretroviral
      therapy for families affected by HIV, as well as emphasize the importance of
      building supportive caregiver-child relationships to decrease the psychological
      symptoms and impact of other life stressors experienced by youth affected by HIV
      in Haiti and similar resource-limited settings.

PMID- 25950917
TI  - Blood flow assessed by color Doppler imaging in retinopathy of prematurity.
AB  - OBJECTIVE: To quantify central retinal arterial and venous blood flow using
      ultrasound color Doppler imaging. STUDY DESIGN: In this prospective observational
      study, eyes of eight preterm infants with retinopathy of prematurity stage 2 and
      of eight preterm infants without retinopathy (gestational age <30 weeks, birth
      weight <1500 g) were evaluated by color Doppler imaging. RESULT: Ocular blood
      flow velocities measured at 28+/-1 days of life did not differ significantly in
      the eyes of preterm infants who subsequently did and did not develop retinopathy.
      Development of retinopathy was associated with highly significant (P<0.0001 each)
      increases in central retinal vein maximum velocities (from 1.99+/-0.36 to 3.72+/
      0.61 cm s(-1)), central retinal artery systolic flow velocities (from 6.44+/-1.52
      to 9.87+/-1.99 cm s(-1)) and flow velocity integrals (from 1.27+/-0.30 to 2.17+/
      0.50 cm) at 64+/-13 days of life. In infants without retinopathy, no significant
      changes were observed except for an increase in central retinal vein maximum
      velocities (from 1.96+/-0.22 to 2.62+/-0.44 cm s(-1), P=0.003). CONCLUSION:
      Retinopathy of prematurity appears to be accompanied by increased retinal blood
      flow.

PMID- 25950918
TI  - Depth of bacterial invasion in resected intestinal tissue predicts mortality in
      surgical necrotizing enterocolitis.
AB  - OBJECTIVE: Up to a third of all infants who develop necrotizing enterocolitis
      (NEC) require surgical resection of necrotic bowel. We hypothesized that the
      histopathological findings in surgically resected bowel can predict the clinical
      outcome of these infants. STUDY DESIGN: We reviewed the medical records and
      archived pathology specimens from all patients who underwent bowel
      resection/autopsy for NEC at a regional referral center over a 10-year period.
      Pathology specimens were graded for the depth and severity of necrosis,
      inflammation, bacteria invasion and pneumatosis, and histopathological findings
      were correlated with clinical outcomes. RESULT: We performed clinico-pathological
      analysis on 33 infants with confirmed NEC, of which 18 (54.5%) died. Depth of
      bacterial invasion in resected intestinal tissue predicted death from NEC (odds
      ratio 5.39 per unit change in the depth of bacterial invasion, 95% confidence
      interval 1.33 to 21.73). The presence of transmural necrosis and bacteria in the
      surgical margins of resected bowel was also associated with increased mortality.
      CONCLUSION: Depth of bacterial invasion in resected intestinal tissue predicts
      mortality in surgical NEC.

PMID- 25950919
TI  - Trends in treatment and in-hospital mortality for neonates with congenital
      diaphragmatic hernia.
AB  - OBJECTIVE: We performed a retrospective cohort study in order to examine recent
      trends in use of post-partum treatments and in-hospital mortality for congenital
      diaphragmatic hernia (CDH). STUDY DESIGN: Included were infants with CDH, born in
      2003 to 2012 and hospitalized at ?7 days of age at one of 33 United States
      tertiary referral children's hospitals with extracorporeal membrane oxygenation
      (ECMO) programs. In-hospital mortality as well as use of ECMO, surfactant and a
      variety of vasodilators were examined for trends during the study period. RESULT:
      Inclusion criteria were met by 3123 infants with CDH. Among 2423 term or near
      term infants, odds of death decreased annually for those with isolated or complex
      CDH. For 700 premature or low-birth weight infants with CDH, in-hospital
      mortality did not change. Among treatments for CDH, increasing with time in the
      study cohort were use of milrinone and sildenafil individually, and use of
      multiple vasodilators during the hospitalization. CONCLUSION: Survival improved
      in large subgroups of term or near-term infants with CDH in this 10-year
      multicenter cohort, temporally associated with increasing use of multiple
      vasodilators. Use of vasodilators for infants with CDH is increasing despite a
      lack of evidence supporting efficacy or safety. Prospective research is needed to
      clarify specific causal effects contributing to improving survival in these
      infants.

PMID- 25950920
TI  - Outcomes of neonates with birth weight?500 g: a 20-year experience.
AB  - OBJECTIVE: Ethical dilemmas continue regarding resuscitation versus comfort care
      in extremely preterm infants. Counseling parents and making decisions regarding
      the care of these neonates should be based on reliable, unbiased and
      representative data drawn from geographically defined populations. We reviewed
      survival and morbidity data for our population at the edge of viability. STUDY
      DESIGN: A retrospective review of our perinatal database was carried out to
      identify all infants born alive and admitted to the neonatal intensive care unit
      (NICU) with BW?500 g between 1989 and 2009. Data from the initial hospital stay
      and follow-up at 24 months were collected. RESULT: Out of 22 672 NICU admissions,
      273 were eligible: 212 neonates were reviewed after excluding infants with
      comfort care. BW ranged from 285 to 500 g (mean 448 g) and gestational age range
      22 to 28 weeks (median 24 week). Sixty-one (28.8%) survived until discharge. Only
      13.8% males survived compared with 39.2% females (P<0.05). Half (49%) were
      discharged with home oxygen/monitor. Fifty (82%) patients' charts were available
      to review at the 24-month follow-up. Thirty-three percent of surviving infants
      had a normal neurodevelopmental assessment at 24 months. Forty-three percent had
      weight/head circumference<5th percentile at 24 months. CONCLUSION: About a third
      of neonates admitted to NICU with ?500 g BW survived, with 33% of those
      surviving, demonstrating age-appropriate development at a 24-month follow-up
      visit.

PMID- 25950921
TI  - Mobility of indaziflam influenced by soil properties in a semi-arid area.
AB  - Indaziflam, a broad-spectrum, pre-emergence herbicide was the focus of a field
      investigation conducted after the identification of sporadic injury symptoms on
      the pecan trees a few months after the application. The study was conducted in
      two pecan orchards located in southern New Mexico, USA, and southeastern Arizona,
      USA. The objectives of this study were to evaluate the occurrence and
      distribution of indaziflam in the soil profile of areas where pecan trees were
      injured (impacted) and areas where no injury symptoms were observed (unimpacted),
      and to determine the relationship between indaziflam concentrations and soil
      properties in those locations. Soil samples were collected, one year after
      applications, from six depth representing 0-7, 7-15, 15-30, 30-60, 60-90 and 90
      120 cm depth to determine the concentration of indaziflam in impacted and
      unimpacted areas of the two orchards. Soil samples were analyzed to determine
      texture, bulk density, organic matter content, cation exchange capacity, pH,
      nitrate, chloride and calcium concentrations. The detection frequency of
      indaziflam was higher in Arizona than in New Mexico, likely due to the
      differences between the tillage practices and sand contents of the orchards. No
      significant correlations were observed between indaziflam and soil properties,
      however indaziflam was mostly detected in areas where pecan trees were unimpacted
      probably as result of greater organic matter content and soil porosity. More
      research is needed to understand the causes of injury to pecan trees by
      indaziflam application. 

PMID- 25950922
TI  - Ileostomy closure in an enhanced recovery setting.
AB  - AIM: Hospital stays of 5 days or more are not uncommon following ileostomy
      closure, yet within an enhanced recovery programme (ERP) it is possible for
      patients to be discharged on the first postoperative day following anterior
      resection. The aim of this study was to evaluate whether the introduction of an
      ERP for ileostomy closure reduced hospital stay without affecting morbidity or
      readmission rates. METHOD: Consecutive patients undergoing elective ileostomy
      closure from October 2000 to March 2013 were included in this study. The data
      were collected prospectively into a database. Enhanced recovery was introduced
      for all elective ileostomy closures in June 2010. Demographic data, length of
      stay (LOS), readmission, morbidity and mortality were compared between the two
      groups using the Mann-Whitney U-test and Fisher's exact test. RESULTS: One
      hundred and forty-five patients underwent elective ileostomy closure during the
      study period (37 ERP and 108 pre-ERP). There were no differences between the two
      groups with respect to demographics, American Society of Anesthesiologists grade,
      prior radiotherapy or chemotherapy, operative time, body mass index, antibiotic
      use or closure method. Readmission rates (5% vs 6.5%, P = 1.0), morbidity (8% vs
      10%, P = 1.0) and mortality (0% vs 0%) were not significantly different. Median
      (2 vs 4 days, P < 0.0001) and mean (3.4 vs 5.6 days, P = 0.033) LOS were
      significantly shorter in the ERP group compared with the pre-ERP group.
      CONCLUSION: An ERP for closure of ileostomy significantly reduces LOS without
      adverse effects for patients.

PMID- 25950923
TI  - Using the World Health Organization Measles Programmatic Risk Assessment Tool for
      Monitoring of Supplemental Immunization Activities in the Philippines.
AB  - In 2012, the World Health Organization Regional Committee for the Western Pacific
      Region (WPR) reaffirmed its commitment to eliminate measles and urged WPR member
      states to interrupt endemic measles virus transmission as rapidly as possible. In
      2013, a large measles outbreak occurred in the Philippines despite implementation
      of measles elimination strategies including a nationwide supplemental
      immunization activity (SIA) in 2011 using measles- and rubella-containing vaccine
      and targeting children aged nine months to seven years. To prevent future measles
      outbreaks a new tool was developed to assess district-level risk for measles
      outbreaks, based on the WPR polio risk assessment tool previously applied in the
      Philippines. Risk was assessed as a function of combined indicator scores from
      four data input categories: population immunity, surveillance quality, program
      performance, and threat assessment. On the basis of the overall score, the tool
      assigned each district a risk category of low, medium, high, or very high. Of the
      122 districts and highly urbanized cities in the Philippines, 58 (48%) were
      classified as high risk or very high risk, including the district of the Metro
      Manila area and Region 4A where the outbreak began in 2013. Risk assessment
      results were used to guide the monitoring and supervision during the nationwide
      SIA conducted in 2014. The initial tool drafted in the Philippines served as a
      template for development of the global risk assessment tool. Regular annual
      measles programmatic risk assessments can be used to help plan risk mitigation
      activities and measure progress toward measles elimination.

PMID- 25950924
TI  - Patients' perspectives on the role of their complaints in the regulatory process.
AB  - BACKGROUND: Governments in several countries are facing problems concerning the
      accountability of regulators in health care. Questions have been raised about how
      patients' complaints should be valued in the regulatory process. However, it is
      not known what patients who made complaints expect to achieve in the process of
      health-care quality regulation. OBJECTIVE: To assess expectations and experiences
      of patients who complained to the regulator. DESIGN: Interviews were conducted
      with 11 people, and a questionnaire was submitted to 343 people who complained to
      the Dutch Health-care Inspectorate. The Inspectorate handled 92 of those
      complaints. This decision was based on the idea that the Inspectorate should only
      deal with complaints that relate to 'structural and severe' problems. RESULTS:
      The response rate was 54%. Self-reported severity of physical injury of
      complaints that were not handled was significantly lower than of complaints that
      were. Most respondents felt that their complaint indicated a structural and
      severe problem that the Inspectorate should act upon. The desire for penalties or
      personal satisfaction played a lesser role. Only a minority felt that their
      complaint had led to improvements in health-care quality. CONCLUSIONS: Patients
      and the regulator share a common goal: improving health-care quality. However,
      patients' perceptions of the complaints' relevance differ from the regulator's
      perceptions. Regulators should favour more responsive approaches, going beyond
      assessing against exclusively clinical standards to identify the range of social
      problems associated with complaints about health care. Long-term learning
      commitment through public participation mechanisms can enhance accountability and
      improve the detection of problems in health care.

PMID- 25950926
TI  - Is diabetes a predictor of worse outcome for spontaneous intracerebral
      hemorrhage?
AB  - BACKGROUND AND PURPOSE: Diabetes is common in acute stroke and is associated with
      worse outcome in ischemic stroke, but its influence on intracerebral hemorrhage
      (ICH) remains controversial. We examined the association between diabetes and
      clinical outcome in a large hospitalized population of Chinese patients with ICH.
      METHODS: We prospectively enrolled patients with ICH who were admitted within 3
      days of stroke onset from March 2002 to December 2010. Data were analyzed on
      demographic and clinical characteristics such as age, gender, vascular risk
      factors, Glasgow Coma Scale (GCS) score at admission, site of hemorrhage and
      surgical treatment. Patient characteristics, functional outcome according to the
      modified Rankin scale (mRS) and mortality were compared between patients with and
      without diabetes. RESULTS: Of the 1438 ICH patients included, 118 (8.2%) had
      diabetes and this subgroup showed a significantly higher proportion of
      hypertension (OR=1.98, 95% CI 1.33-2.96, P=0.001) and hyperlipidemia (OR=3.22,
      95% CI 1.16-8.89, P=0.024). Patients were followed up for a mean of 147.48 +/-
      3.59 days. Cox regression suggested that diabetes was not a significant predictor
      of mortality in our cohort (P>0.05), and repeated-measures ANOVA showed that
      variance in mRS over the course of follow-up was similar between patients with
      and without diabetes (P=0.463). CONCLUSION: Our data suggest that diabetes in
      Chinese patients with ICH is not associated with increased mortality or
      functional outcome. Future studies are needed to clarify possible confounders
      affecting prognosis after ICH.

PMID- 25950925
TI  - Recurrence rates and functional outcome after resection of intrinsic
      intramedullary tumors.
AB  - INTRODUCTION: Intramedullary tumors account for 2-4% of all CNS neoplasms.
      Surgical resection is challenging because of aggravated neurological impairment
      in up to 64% of patients. We analyzed a consecutive series of patients with
      intramedullary tumors and focused on the extent of resection, functional outcome,
      and tumor recurrence. METHODS: 53 patients (23 women and 30 men; mean age 46.3
      years) were included who had undergone microsurgical resection for intramedullary
      spinal tumors. We reviewed the patient records for tumor size, edema,
      intratumoral hemorrhage, consistency, midline detection, resection method, extent
      of resection, histopathology, and recurrence. Outcome was measured by the
      Karnofsky Score (KPI), the McCormick score (MCS), and the Medical Research
      Council Neurological Performance Score (MRC-NPS). RESULTS: The most frequent
      diagnosis was ependymoma (37.7%), lymphoma (13.2%) and astrocytoma (11.3%). The
      majority of tumors were located in the thoracic spine (62.2%). Gross total
      resection was achieved in 73.6% and most successful in patients with ependymal
      histology (p<0.01). Tumor recurrence - observed in 11.3% - was significantly
      associated with age >65 years, astrocytic histology, higher tumor grades, and
      higher Ki-67 labeling. At follow-up, MCS and MRC-NPS showed significantly better
      results than prior to resection (p<0.001), and pain and sensory deficits had
      improved in 67.9% and 64.2% of patients, respectively. Microsurgical resection
      improved the neurological status significantly. Pain and sensory deficits showed
      higher improvement rates than paresis and vegetative dysfunction. CONCLUSION: Our
      data help identify patients at risk of tumor recurrence and classify the course
      of postoperative neurological performance.

PMID- 25950928
TI  - Correction: Dose-Dependent ATP Depletion and Cancer Cell Death following Calcium
      Electroporation, Relative Effect of Calcium Concentration and Electric Field
      Strength.

PMID- 25950927
TI  - Prostatic arterial embolization for the treatment of lower urinary tract symptoms
      as a result of large benign prostatic hyperplasia: A prospective single-center
      investigation.
AB  - OBJECTIVE: To evaluate the effectiveness and safety of prostatic arterial
      embolization as a primary treatment for patients with lower urinary tract
      symptoms as a result of large benign prostatic hyperplasia. METHODS: A total of
      64 patients with prostates >80 mL were included in the study. Prostatic arterial
      embolization was carried out using a combination of 50-um and 100-um particles.
      Clinical follow up was carried out using the International Prostate Symptom
      Score, quality of life, peak urinary flow, postvoid residual volume,
      International Index of Erectile Function Short Form, prostate-specific antigen,
      and prostatic volume at 1, 3, 6 and every 6 months thereafter. RESULTS: Prostatic
      arterial embolization was technically successful in 60 of 64 patients (93.8%).
      Follow-up data were available for 60 patients with a mean of 18 months. A
      clinical improvement, defined as reduction of International Prostate Symptom
      Score and increase of peak urinary flow, at 1 month, 3 months, 6 months, 12
      months and 24 months, was achieved in 95.0%, 95.0%, 93.3%, 92.6% and 90.5%,
      respectively. A total of 42 patients had completed the follow up at 24 months
      after prostatic arterial embolization. There was an improvement in terms of mean
      International Prostate Symptom Score (pre-prostatic arterial embolization vs post
      prostatic arterial embolization 27.0 vs 8.0; P < 0.01), mean quality of life (5.5
      vs 2.0; P < 0.01), mean peak urinary flow (7.0 vs 13.0; P < 0.01), mean postvoid
      residual volume (130 vs 45.0; P < 0.05) and prostatic volume (121.0 vs 71.5,
      reduction of 40.9%; P < 0.01) were significantly different with respect to
      baseline. CONCLUSION: Prostatic arterial embolization seems to be a safe and
      effective treatment method for patients with lower urinary tract symptoms as a
      result of large benign prostatic hyperplasia, and it might play an important role
      for patients in whom medical therapy has failed, who are not candidates for
      surgical treatment.

PMID- 25950929
TI  - Fast monitoring of indoor bioaerosol concentrations with ATP bioluminescence
      assay using an electrostatic rod-type sampler.
AB  - A culture-based colony counting method is the most widely used analytical
      technique for monitoring bioaerosols in both indoor and outdoor environments.
      However, this method requires several days for colony formation. In this study,
      our goal was fast monitoring (Sampling: 3 min, Detection: < 1 min) of indoor
      bioaerosol concentrations with ATP bioluminescence assay using a bioaerosol
      sampler. For this purpose, a novel hand-held electrostatic rod-type sampler (110
      mm wide, 115 mm long, and 200 mm tall) was developed and used with a commercial
      luminometer, which employs the Adenosine triphosphate (ATP) bioluminescence
      method. The sampler consisted of a wire-rod type charger and a cylindrical
      collector, and was operated with an applied voltage of 4.5 kV and a sampling flow
      rate of 150.7 lpm. Its performance was tested using Staphylococcus epidermidis
      which was aerosolized with an atomizer. Bioaerosol concentrations were measured
      using ATP bioluminescence method with our sampler and compared with the culture
      based method using Andersen cascade impactor under controlled laboratory
      conditions. Indoor bioaerosol concentrations were also measured using both
      methods in various indoor environments. A linear correlation was obtained between
      both methods in lab-tests and field-tests. Our proposed sampler with ATP
      bioluminescence method may be effective for fast monitoring of indoor bioaerosol
      concentrations. 

PMID- 25950930
TI  - Mach-Zehnder interferometer (MZI) point-of-care system for rapid multiplexed
      detection of microRNAs in human urine specimens.
AB  - MicroRNAs have been identified as promising biomarkers for human diseases. The
      development of a point-of-care (POC) test for the disease-associated miRNAs would
      be especially beneficial, since miRNAs are unexpectedly well preserved in various
      human specimens, including urine. Here, we present the Mach-Zehnder
      interferometer-miRNA detection system capable of detecting multiple miRNAs in
      clinical urine samples rapidly and simultaneously in a label-free and real-time
      manner. Through measurement of the light phase change, the MZI sensor provides an
      optical platform for fast profiling of small molecules with improved accuracy. We
      demonstrate that this system could specifically detect target miRNAs (miR-21, and
      let-7a), and even identify the single nucleotide polymorphism of the let-7 family
      of miRNAs from synthetic and cell line samples. The clinical applicability of
      this system is confirmed by simultaneously detecting two types of miRNAs in urine
      samples of bladder cancer patients in a single reaction, with a detection time of
      15 min. The POC system can be expanded to detect a number of miRNAs of different
      species and should be useful for a variety of clinical applications requiring at
      or near the site of patient care.

PMID- 25950931
TI  - Porphyrinic metal-organic framework as electrochemical probe for DNA sensing via
      triple-helix molecular switch.
AB  - An electrochemical DNA sensor was developed based on the electrocatalysis of
      porphyrinic metal-organic framework (MOF) and triple-helix molecular switch for
      signal transduction. The streptavidin functionalized zirconium-porphyrin MOF (PCN
      222@SA) was prepared as signal nanoprobe via covalent method and demonstrated
      high electrocatalysis for O2 reduction. Due to the large steric effect, the
      designed nanoprobe was blocked for the interaction with the biotin labeled triple
      helix immobilized on the surface of glassy carbon electrode. In the presence of
      target DNA, the assistant DNA in triple-helix will hybridize with target DNA,
      resulting in the disassembly of triple-helix molecular. Consequently, the end
      biotin away from the electrode was ''activated'' for easy access to the signal
      nanoprobe, PCN-222@SA, on the basis of biotin-streptavidin biorecognition. The
      introduction of signal nanoprobe to a sensor surface led to a significantly
      amplified electrocatalytic current towards oxygen reduction. Integrating with DNA
      recycling amplification of Exonuclease III, the sensitivity of the biosensor was
      improved significantly with detection limit of 0.29 fM. Moreover, the present
      method has been successfully applied to detect DNA in complex serum matrix. This
      porphyrinic MOF-based strategy has promising application in the determination of
      various analytes for signal transduction and has great potential in bioassays.

PMID- 25950932
TI  - A microfluidic chip integrated with a high-density PDMS-based microfiltration
      membrane for rapid isolation and detection of circulating tumor cells.
AB  - Isolation of circulating tumor cells (CTCs) by size exclusion is a widely
      researched technique that offers the advantage of capturing tumor cells without
      reliance on cell surface expression markers. In this work, we report the
      development of a novel polydimethylsiloxane (PDMS) membrane filter-based
      microdevice for rapid and highly efficient isolation of CTCs from peripheral
      blood. A precise and highly porous PDMS microfilter was fabricated and integrated
      into the microfiltration chip by combining a sacrificial transferring film with a
      sandwich molding method. We achieved >90% recovery when isolating lung cancer
      cells from spiked blood samples, with a relatively high processing throughput of
      10 mL/h. In contrast to existing CTC filtration systems, which rely on low
      porosity track-etch filters or expensive lithography-based filters, our
      microfiltration chip does not require complex e-beam lithography or the reactive
      ion etching process, therefore it offers a low-cost alternative tool for highly
      efficient CTC enrichment and in situ analysis. Thus, this new microdevice has the
      potential for use in routine monitoring of cancer development and cancer therapy
      in a clinical setting.

PMID- 25950933
TI  - In situ formation of graphene layers on graphite surfaces for efficient anodes of
      microbial fuel cells.
AB  - Graphene can be used to improve the performance of the anode in a microbial fuel
      cell (MFC) due to its good biocompatibility, high electrical conductivity and
      large surface area. However, the chemical production and modification of the
      graphene on the anode are environmentally hazardous because of the use of various
      harmful chemicals. This study reports a novel method based on the electrochemical
      exfoliation of a graphite plate (GP) for the in situ formation of graphene layers
      on the surface of a graphite electrode. When the resultant graphene-layer-based
      graphite plate electrode (GL/GP) was used as an anode in an MFC, a maximum power
      density of 0.67 +/- 0.034 W/m(2) was achieved. This value corresponds to 1.72-,
      1.56- and 1.26-times the maximum power densities of the original GP, exfoliated
      graphene-modified GP (EG/GP) and chemically-reduced-graphene-modified GP (rGO/GP)
      anodes, respectively. Electrochemical measurements revealed that the high
      performance of the GL/GP anode was attributable to its macroporous structure,
      improved electron transfer and high electrochemical capacitance. The results
      demonstrated that the proposed method is a facile and environmentally friendly
      synthesis technique for the fabrication of high-performance graphene-based
      electrodes for use in microbial energy harvesting.

PMID- 25950934
TI  - An ultrasensitive electrochemical immunosensor for apolipoprotein E4 based on
      fractal nanostructures and enzyme amplification.
AB  - Human apolipoprotein E4 (APOE4) is a major risk factor for Alzheimer's disease
      (AD) and can greatly increase the morbidity. In this work, an ultrasensitive
      sandwich-type electrochemical immunosensor for the quantitative detection of
      APOE4 was designed based on fractal gold (FracAu) nanostructures and enzyme
      amplification. The FracAu nanostructures were directly electrodeposited by
      hydrogen tetrachloroaurate (HAuCl4) on polyelectrolytes modified indium tin oxide
      (ITO) electrode. The sensing performances of the modified interface were
      investigated by cyclic voltammetry (CV). After functionalization with HRP-labeled
      APOE4 antibody, the human APOE4 could be detected quantitatively by current
      response. The current response has a linear relationship with the logarithm of
      human APOE4 concentrations in a range from 1.0 to 10,000.0 ng/mL, with a
      detection limit of 0.3 ng/mL. The fabricated APOE4 electrochemical immunosensor
      exhibits strong specificity, high sensitivity, low detection limit and wide
      linear range. The detection of human APOE4 provides a strong support for the
      prevention of AD and early-stage warning for those susceptible populations.

PMID- 25950935
TI  - Highly selective and sensitive detection of miRNA based on toehold-mediated
      strand displacement reaction and DNA tetrahedron substrate.
AB  - MicroRNAs (miRNAs) play important roles in a variety of biological processes and
      have been regarded as tumor biomarkers in cancer diagnosis and prognosis. In this
      work, a single-molecule counting method for miRNA analysis was proposed based on
      toehold-mediated strand displacement reaction (SDR) and DNA tetrahedron
      substrate. Firstly, a specially designed DNA tetrahedron was assembled with a
      hairpin at one of the vertex, which has an overhanging toehold domain. Then, the
      DNA tetrahedron was immobilized on the epoxy-functional glass slide by epoxy
      amine reaction, forming a DNA tetrahedron substrate. Next, the target miRNA
      perhybridized with the toehold domain and initiated a strand displacement
      reaction along with the unfolding of the hairpin, realizing the selective
      recognization of miRNA. Finally, a biotin labeled detection DNA was hybridized
      with the new emerging single strand and the streptavidin coated QDs were used as
      fluorescent probes. Fluorescent images were acquired via epi-fluorescence
      microscopy, the numbers of fluorescence dots were counted one by one for
      quantification. The detection limit is 5 fM, which displayed an excellent
      sensitivity. Moreover, the proposed method which can accurately be identified the
      target miRNA among its family members, demonstrated an admirable selectivity.
      Furthermore, miRNA analysis in total RNA samples from human lung tissues was
      performed, suggesting the feasibility of this method for quantitative detection
      of miRNA in biomedical research and early clinical diagnostics.

PMID- 25950936
TI  - Electrochemiluminescence immunosensor based on multifunctional luminol-capped
      AuNPs@Fe3O4 nanocomposite for the detection of mucin-1.
AB  - In this work, a novel and multifunctional nanocomposite of luminol capped gold
      modified Fe3O4 (Lu-AuNPs@Fe3O4) was utilized as the carrier of secondary antibody
      (Ab2) to fabricate a sandwiched electrochemiluminescence (ECL) immunosensor for
      ultrasensitive detection of mucin-1 (MUC1). Herein, the luminol capped gold
      nanoparticles (Lu-AuNPs) were synthesized with HAuCl4 and luminol by the help of
      NaBH4 at room temperature, and then Lu-AuNPs were adsorbed on the Fe3O4 magnetic
      nanoparticles (MNPs) to form the nanocomposite of Lu-AuNPs@Fe3O4 via
      electrostatic interaction. Fe3O4 MNPs in Lu-AuNPs@Fe3O4 exhibited excellent
      conductivity and admirable catalytic activity in H2O2 decomposition, which could
      enhance the ECL efficiency of luminol-H2O2 system. In addition, the substrates of
      gold coated ZnO nanoparticles (AuNPs@ZnO), providing large specific surface areas
      for primary antibody (Ab1) capturing, were modified on the electrode. As a
      result, a wide linear range of 7 orders of magnitude from 10 fg/mL to 10 ng/mL
      was obtained with an ultralow detection limit of 4.5 fg/mL for MUC1.

PMID- 25950937
TI  - Carbon nanotube/polymer composite electrodes for flexible, attachable
      electrochemical DNA sensors.
AB  - All-solution-processed, easily-made, flexible multi-walled carbon nanotube
      (MWCNT)/polydimethylsiloxane (PDMS)-based electrodes were fabricated and used for
      electrochemical DNA sensors. These electrodes could serve as a recognition layer
      for DNA, without any surface modification, through pi-pi interactions between the
      MWCNTs and DNA, greatly simplifying the fabrication process for DNA sensors. The
      electrodes were directly connected to an electrochemical analyzer in the
      differential pulse voltammetry (DPV) and cyclic voltammetry (CV) measurements,
      where methylene blue was used as a redox indicator. Since neither functional
      groups nor probe DNA were immobilized on the surfaces of the electrodes, the
      sensor can be easily regenerated by washing these electrodes with water. The
      limit of detection was found to be 1.3 * 10(2)pM (S/N=3), with good DNA sequence
      differentiation ability. Fast fabrication of a DNA sensor was also achieved by
      cutting and attaching the MWCNT-PDMS composite electrodes at an analyte solution
      containable region. Our results pave the way for developing user-fabricated
      easily attached DNA sensors at low costs.

PMID- 25950939
TI  - Linear light-scattering of gold nanostars for versatile biosensing of nucleic
      acids and proteins using exonuclease III as biocatalyst to signal amplification.
AB  - Gold nanomaterials promise a wide range of potential applications in chemical and
      biological sensing, imaging, and catalysis. In this paper, we demonstrate a
      facile method for room-temperature synthesis of gold nanostars (AuNSs) with a
      size of ~50 nm via seeded growth. Significantly, the AuNSs are found to have high
      light-scattering properties, which are successfully used as labels for sensitive
      and selective detection of nucleic acids and proteins by using exonuclease III
      (Exo III) as a biocatalyst. For DNA detection, the binding of targets to the
      functionalized AuNS probes leads to the Exo III-stimulated cascade recycling
      amplification. As a result, a large amount of AuNSs are released from magnetic
      nanoparticles (MNPs) into solution, providing a greatly enhanced light-scattering
      signal for amplified sensing process. Moreover, a binding-induced DNA three-way
      junction (DNA TWJ) is introduced to thrombin detection, in which the binding of
      two aptamers to thrombin triggers assembly of the DNA motifs and initiates the
      subsequent DNA strand displacement reaction (SDR) and Exo III-assisted cascade
      recycling amplification. The detection limits of 89 fM and 5.6 pM are achieved
      for DNA and thrombin, respectively, which are comparable to or even exceed that
      of the reported isothermal amplification methods. It is noteworthy that based on
      the DNA TWJ strategy the sequences are independent on target proteins.
      Additionally, the employment of MNPs in the assays can not only simplify the
      operations but also improve the detection sensitivity. Therefore, the proposed
      amplified light-scattering assay with high sensitivity and selectivity,
      acceptable accuracy, and satisfactory versatility of analytes provides various
      applications in bioanalysis.

PMID- 25950938
TI  - Lignin as immobilization matrix for HIV p17 peptide used in immunosensing.
AB  - Immunosensors based on electrical impedance spectroscopy (EIS) are increasingly
      being used as a fast and potentially low cost method for clinical diagnostics. In
      this work we fabricated immunosensors by depositing layer-by-layer (LbL) films
      made with an antigenic peptide (p17-1) sequence (H2N-LSGGELDRWEKIRLRPGG-OH) and
      lignin on interdigitated gold electrodes, which could detect anti-p17 (HIV, human
      immune deficiency virus) antibodies (Ab) in phosphate buffered solutions (PBS).
      The molecular recognition interaction between the peptide (p17-1) and the
      specific Ab (anti-p17) yielded substantial changes in morphology of the with LbL
      films, with increased roughness according to atomic force microscopy data. This
      interaction is behind the high sensitivity of the immunosensor. Indeed, from the
      EIS results, we noted that the capacitance increased significantly with the
      specific Ab concentration, before getting close to saturation of available
      peptide sites at high concentrations. Concentrations of specific antibodies as
      low as 0.1 ng/mL could be detected and the immunosensors had their activity
      preserved for two months at least. The selectivity of the immunosensor was
      confirmed with two types of control experiments. First, no changes in impedance
      were observed when the lignin/peptide LbL immunosensor was immersed into a PBS
      solution containing the non-specific Ab (anti-HCV for Hepatitis C) antibodies.
      Furthermore, for sensing units made LbL films of lignin only, the electrical
      response was not affected by adding specific antibodies into the PBS buffer. The
      successful immunosensing for HIV with antigenic peptides in a lignin matrix is
      also relevant for valorization of lignin, which is an important biomass component
      in the sugar and ethanol industry, and brings the prospect for all-organic,
      biocompatible sensors if implantation is ever required.

PMID- 25950940
TI  - A novel ultrasensitive electrochemical DNA sensor based on double tetrahedral
      nanostructures.
AB  - Electrochemical DNA (E-DNA) sensor is an important tool for detecting DNA
      biomarker. In this work, we have demonstrated a novel strategy of E-DNA sensor
      based on DNA tetrahedral nanostructures for the sensitive detection of target
      DNA. In our design, thiol and biotin modified DNA tetrahedral nanostructures were
      used as capture and report probes respectively. The biotin-tagged three
      dimensional DNA tetrahedral nanostructures were employed for efficient signal
      amplification by capturing multiple catalytic enzymes. Such improved E-DNA sensor
      can sensitively detect DNA target as low as 1 fM with excellent differentiation
      ability for even single mismatch. And a mean recovery rate of 90.57% in DNA
      solution extracted from human serum was obtained. We have also compared this new
      method of attaching catalytic enzymes with the other two typical methods: One is
      through biotinylated single-stranded DNA (SSDNA) and the other is through gold
      nanoparticles (GNPs). Results indicated that the RTSPs-based enzyme amplification
      system showed much better performance than the other two systems.

PMID- 25950941
TI  - Sensitive detection for coralyne and mercury ions based on homo-A/T DNA by
      exonuclease signal amplification.
AB  - Based on specific homo-A/T DNA binding properties, a strategy for coralyne and
      mercury ions detection was realised by exonuclease-aided signal amplification.
      Coralyne could specifically bind homo-A DNA and protect it from the hydrolysis of
      exonuclease I. The coralyne-protected DNA was subsequently used as a trigger
      strand to hydrolyze DNA2 in exonuclease-aided signal amplification process.
      Thiazole orange was used to quantify the remainder DNA2. Under the optimal
      condition, the fluorescence intensity was linearly proportional to the
      concentration of coralyne in the range of 0.2-100 nM with a limit of detection
      (LOD) of 0.31 nM, which presented the lowest LOD for coralyne among all reported.
      With homo-T and Hg(2+) taking the place of homo-A DNA and coralyne, respectively,
      the system could also be used for Hg(2+) detection. The experiments in real
      samples also showed good results. This method was label-free, low-cost, easy
      operating and highly repeatable for the detection of coralyne and mercury ions.
      It could also be extended to detect various analytes, such as other metal ions,
      proteins and small molecules by using appropriate aptamers.

PMID- 25950942
TI  - Real-time quantitative monitoring of hiPSC-based model of macular degeneration on
      Electric Cell-substrate Impedance Sensing microelectrodes.
AB  - Age-related macular degeneration (AMD) is the leading cause of blindness in the
      developed world. Humanized disease models are required to develop new therapies
      for currently incurable forms of AMD. In this work, a tissue-on-a-chip approach
      was developed through combining human induced pluripotent stem cells, Electric
      Cell-substrate Impedance Sensing (ECIS) and reproducible electrical wounding
      assays to model and quantitatively study AMD. Retinal Pigment Epithelium (RPE)
      cells generated from a patient with an inherited macular degeneration and from an
      unaffected sibling were used to test the model platform on which a reproducible
      electrical wounding assay was conducted to model RPE damage. First, a robust and
      reproducible real-time quantitative monitoring over a 25-day period demonstrated
      the establishment and maturation of RPE layers on the microelectrode arrays. A
      spatially controlled RPE layer damage that mimicked cell loss in AMD disease was
      then initiated. Post recovery, significant differences (P < 0.01) in migration
      rates were found between case (8.6 +/- 0.46 MUm/h) and control cell lines (10.69
      +/- 0.21 MUm/h). Quantitative data analysis suggested this was achieved due to
      lower cell-substrate adhesion in the control cell line. The ECIS cell-substrate
      adhesion parameter (alpha) was found to be 7.8 +/- 0.28 Omega(1/2)cm for the case
      cell line and 6.5 +/- 0.15 Omega(1/2)cm for the control. These findings were
      confirmed using cell adhesion biochemical assays. The developed disease model-on
      a-chip is a powerful platform for translational studies with considerable
      potential to investigate novel therapies by enabling real-time, quantitative and
      reproducible patient-specific RPE cell repair studies.

PMID- 25950943
TI  - CK2-regulated schwannomin-interacting protein IQCJ-SCHIP-1 association with AnkG
      contributes to the maintenance of the axon initial segment.
AB  - The axon initial segment (AIS) plays a central role in electrogenesis and in the
      maintenance of neuronal polarity. Its molecular organization is dependent on the
      scaffolding protein ankyrin (Ank) G and is regulated by kinases. For example, the
      phosphorylation of voltage-gated sodium channels by the protein kinase CK2
      regulates their interaction with AnkG and, consequently, their accumulation at
      the AIS. We previously showed that IQ motif containing J-Schwannomin-Interacting
      Protein 1 (IQCJ-SCHIP-1), an isoform of the SCHIP-1, accumulated at the AIS in
      vivo. Here, we analyzed the molecular mechanisms involved in IQCJ-SCHIP-1
      specific axonal location. We showed that IQCJ-SCHIP-1 accumulation in the AIS of
      cultured hippocampal neurons depended on AnkG expression. Pull-down assays and
      surface plasmon resonance analysis demonstrated that AnkG binds to CK2
      phosphorylated IQCJ-SCHIP-1 but not to the non-phosphorylated protein. Surface
      plasmon resonance approaches using IQCJ-SCHIP-1, SCHIP-1a, another SCHIP-1
      isoform, and their C-terminus tail mutants revealed that a segment including
      multiple CK2-phosphorylatable sites was directly involved in the interaction with
      AnkG. Pharmacological inhibition of CK2 diminished both IQCJ-SCHIP-1 and AnkG
      accumulation in the AIS. Silencing SCHIP-1 expression reduced AnkG cluster at the
      AIS. Finally, over-expression of IQCJ-SCHIP-1 decreased AnkG concentration at the
      AIS, whereas a mutant deleted of the CK2-regulated AnkG interaction site did not.
      Our study reveals that CK2-regulated IQJC-SCHIP-1 association with AnkG
      contributes to AIS maintenance. The axon initial segment (AIS) organization
      depends on ankyrin (Ank) G and kinases. Here we showed that AnkG binds to CK2
      phosphorylated IQCJ-SCHIP-1, in a segment including 12 CK2-phosphorylatable
      sites. In cultured neurons, either pharmacological inhibition of CK2 or IQCJ
      SCHIP-1 silencing reduced AnkG clustering. Overexpressed IQCJ-SCHIP-1 decreased
      AnkG concentration at the AIS whereas a mutant deleted of the CK2-regulated AnkG
      interaction site did not. Thus, CK2-regulated IQJC-SCHIP-1 association with AnkG
      contributes to AIS maintenance. 

PMID- 25950945
TI  - Adsorption mechanisms of emerging micro-pollutants with a clay mineral: Case of
      tramadol and doxepine pharmaceutical products.
AB  - A sodium exchanged smectite clay mineral (Mt) was used as geo-sorbent for the
      adsorption of tramadol and doxepin: two pharmaceutical products (PPs) defined as
      emerging pollutants due to their presence at significant concentration in
      numerous water compartments. The adsorption isotherms for both the temperatures
      of 20 and 40 degrees C and the derived data determined through the fitting
      procedure by using Langmuir, Freundlich and Dubinin-Radushkevich equation models
      explicitly pointed out that the sorption of both tramadol and doxepin is mainly
      driven by electrostatic interaction. The studied PPs are intercalated in a
      monolayer arrangement within the interlayer space through a cation exchange in
      stoichiometric proportion with the Na(+) cations leading to adsorbed PPs amounts
      that match the cation exchange capacity (CEC) of Mt. Due to their hydrophobic
      character, additional doxepin molecules could be adsorbed by weak molecular
      interaction driving to an increase of the adsorbed amount beyond the CEC at low
      temperature (20 degrees C). The confinement of PPs within the interlayer space of
      Mt confirms the use of clay minerals as potential material for the wastewater
      treatment as well as it drives to an amorphous or glassy state, which can find
      echo in biopharmaceutical applications for a controlled release of PPs. 

PMID- 25950946
TI  - Excretory, Secretory, and Tissue Residues after Label and Extra-label
      Administration of Flunixin Meglumine to Saline- or Lipopolysaccharide-Exposed
      Dairy Cows.
AB  - Twenty lactating dairy cattle were intravenously infused with either
      lipopolysaccharide (LPS) (n = 10) or sterile saline (n = 10). Five cattle in each
      group received three doses of flunixin meglumine administered by either
      intravenous infusion or intramuscular injection at 24 h intervals. Milk, urine,
      and tissues were collected. Thirty-six hours after the last flunixin
      administration, milk from six cows contained 5-hydroxyflunixin (5OHF) levels
      greater than the milk tolerance of 2 ng/mL; by 48 h, milk from two cows, a saline
      and a LPS-treated animal, had violative milk concentrations of 5OHF. A single
      animal treated with LPS and intramuscular flunixin contained violative flunixin
      residues in liver. The ratio of urinary flunixin/5OHF was correlated (P < 0.01;
      R(2) = 0.946) with liver flunixin residues in LPS-treated animals, but not (P =
      0.96; R(2) = 0.003) in cows treated with saline in lieu of LPS. Violative
      residues of flunixin in dairy cattle may be related to LPS inhibition of flunixin
      metabolism. 

PMID- 25950948
TI  - First- and Second-Order Stimuli Reaction Time Measures Are Highly Sensitive to
      Mild Traumatic Brain Injuries.
AB  - Mild traumatic brain injury (mTBI) has subtle effects on several brain functions
      that can be difficult to assess and follow up. We investigated the impact of mTBI
      on the perception of sine-wave gratings defined by first- and second-order
      characteristics. Fifteen adults diagnosed with mTBI were assessed at 15 days, 3
      months, and 12 months postinjury. Fifteen matched controls followed the same
      testing schedule. Reaction times (RTs) for flicker detection and motion direction
      discrimination were measured. Stimulus contrast of first- and second-order
      patterns was equated to control for visibility, and correct-response RT means,
      standard deviations (SDs), medians, and interquartile ranges (IQRs) were
      calculated. The level of symptoms was also evaluated to compare it to RT data. In
      general in mTBI, RTs were longer, and SDs as well as IQRs larger, than those of
      controls. In addition, mTBI participants' RTs to first-order stimuli were shorter
      than those to second-order stimuli, and SDs as well as IQRs larger for first-
      than for second-order stimuli in the motion condition. All these observations
      were made over the three sessions. The level of symptoms observed in mTBI was
      higher than that of control participants, and this difference did also persist up
      to 1 year after the brain injury, despite an improvement. The combination of RT
      measures with particular stimulus properties is a highly sensitive method for
      measuring mTBI-induced visuomotor anomalies and provides a fine probe of the
      underlying mechanisms when the brain is exposed to mild trauma. 

PMID- 25950949
TI  - One-Pot Synthesis of Esters of Cyclopropane Carboxylic Acids via Tandem Vicarious
      Nucleophilic Substitution-Michael Addition Process.
AB  - alpha-Chlorocarbanions generated via base-induced vicarious nucleophilic
      substitution reaction of alkyl dichloroacetates with nitroarenes react with
      Michael acceptors to give esters of cyclopropane carboxylic acids substituted
      with p-nitroaromatic rings. 

PMID- 25950944
TI  - Burden analysis of rare microdeletions suggests a strong impact of
      neurodevelopmental genes in genetic generalised epilepsies.
AB  - Genetic generalised epilepsy (GGE) is the most common form of genetic epilepsy,
      accounting for 20% of all epilepsies. Genomic copy number variations (CNVs)
      constitute important genetic risk factors of common GGE syndromes. In our present
      genome-wide burden analysis, large (>= 400 kb) and rare (< 1%) autosomal
      microdeletions with high calling confidence (>= 200 markers) were assessed by the
      Affymetrix SNP 6.0 array in European case-control cohorts of 1,366 GGE patients
      and 5,234 ancestry-matched controls. We aimed to: 1) assess the microdeletion
      burden in common GGE syndromes, 2) estimate the relative contribution of
      recurrent microdeletions at genomic rearrangement hotspots and non-recurrent
      microdeletions, and 3) identify potential candidate genes for GGE. We found a
      significant excess of microdeletions in 7.3% of GGE patients compared to 4.0% in
      controls (P = 1.8 x 10-7; OR = 1.9). Recurrent microdeletions at seven known
      genomic hotspots accounted for 36.9% of all microdeletions identified in the GGE
      cohort and showed a 7.5-fold increased burden (P = 2.6 x 10-17) relative to
      controls. Microdeletions affecting either a gene previously implicated in
      neurodevelopmental disorders (P = 8.0 x 10-18, OR = 4.6) or an evolutionarily
      conserved brain-expressed gene related to autism spectrum disorder (P = 1.3 x 10
      12, OR = 4.1) were significantly enriched in the GGE patients. Microdeletions
      found only in GGE patients harboured a high proportion of genes previously
      associated with epilepsy and neuropsychiatric disorders (NRXN1, RBFOX1, PCDH7,
      KCNA2, EPM2A, RORB, PLCB1). Our results demonstrate that the significantly
      increased burden of large and rare microdeletions in GGE patients is largely
      confined to recurrent hotspot microdeletions and microdeletions affecting
      neurodevelopmental genes, suggesting a strong impact of fundamental
      neurodevelopmental processes in the pathogenesis of common GGE syndromes. 

PMID- 25950947
TI  - Insights into virulence factors determining the pathogenicity of Cronobacter
      sakazakii.
AB  - Cronobacter sakazakii is an opportunistic pathogen associated with outbreaks of
      life-threatening necrotizing enterocolitis, meningitis and sepsis in neonates and
      infants. The pathogen possesses an array of virulence factors which aid in tissue
      adhesion, invasion and host cell injury. Although the identification and
      validation of C. sakazakii virulence factors has been hindered by availability of
      suitable neonatal animal model, various studies has reported outer membrane
      protein A (ompA) as a potential virulence marker. Various other plasmid
      associated genes such as filamentous hemagglutinin (fhaBC), Cronobacter
      plasminogen activator (cpa) and genes responsible for iron acquisition (eitCBAD
      and iucABD/iutA) have been reported in different strains of C. sakazakii. Besides
      these proposed virulence factors, several biophysical growth factors such as
      formation of biofilms and resistance to various environmental stresses also
      contributes to the pathogenic potential of this pathogen. This review provides an
      update on virulence determinants associated with the pathogenesis of C.
      sakazakii. The potential reservoirs of the pathogen, mode of transmission and
      epidemiology are also discussed. 

PMID- 25950950
TI  - ALDH1B1 Is Crucial for Colon Tumorigenesis by Modulating Wnt/beta-Catenin, Notch
      and PI3K/Akt Signaling Pathways.
AB  - In the normal human colon, aldehyde dehydrogenase 1B1 (ALDH1B1) is expressed only
      at the crypt base, along with stem cells. It is also highly expressed in the
      human colonic adenocarcinomas. This pattern of expression corresponds closely to
      that observed for Wnt/beta-catenin signaling activity. The present study examines
      the role of ALDH1B1 in colon tumorigenesis and signalling pathways mediating its
      effects. In a 3-dimensional spheroid growth model and a nude mouse xenograft
      tumor model, shRNA-induced suppression of ALDH1B1 expression decreased the number
      and size of spheroids formed in vitro and the size of xenograft tumors formed in
      vivo by SW 480 cells. Six binding elements for Wnt/beta-catenin signalling
      transcription factor binding elements (T-cell factor/lymphoid enhancing factor)
      were identified in the human ALDH1B1 gene promoter (3 kb) but shown by dual
      luciferase reporter assay to not be necessary for ALDH1B1 mRNA expression in
      colon adenocarcinoma cell lines. We examined Wnt-reporter activity and
      protein/mRNA expression for Wnt, Notch and PI3K/Akt signaling pathways. Wnt/beta
      catenin, Notch and PI3K/Akt-signaling pathways were down-regulated in SW 480
      cells in which ALDH1B1 expression had been suppressed. In summary, our data
      demonstrate that ALDH1B1 may promote colon cancer tumorigenesis by modulating the
      Wnt/beta-catenin, Notch and PI3K/Akt signaling pathways. Selective targeting of
      ALDH1B1 may represent a novel means to prevent or treat colon cancer.

PMID- 25950951
TI  - Communication of Pulmonary Function Test Results: A Survey of Patient's
      Preferences.
AB  - INTRODUCTION: Physician-patient communication in patients suffering from common
      chronic respiratory disease should encompass discussion about pulmonary function
      test (PFT) results, diagnosis, disease education, smoking cessation and
      optimising inhaler technique. Previous studies have identified that patients with
      chronic respiratory disease/s often express dissatisfaction about physician
      communication. Currently there is a paucity of data regarding patient awareness
      of their PFT results (among those who have undergone PFTs previously) or patient
      preferences about PFT result communication. METHODS: We undertook a three-month
      prospective study on outpatients referred to two Pulmonary Function Laboratories.
      If subjects had undergone PFTs previously, the awareness of their previous test
      results was evaluated. All subjects were asked about their preferences for PFT
      result communication. Subjects were determined to have chronic respiratory
      disease based on their past medical history. RESULTS: 300 subjects (50% male)
      with a median age (+/- SD) of 65 (+/- 14) years participated in the study. 99% of
      the study participants stated that they were at least moderately interested in
      knowing their PFT results. 72% (217/300) of the subjects had undergone at least
      one PFT in the past, 48% of whom stated they had not been made aware of their
      results. Fewer subjects with chronic respiratory disease preferred that only a
      doctor discuss their PFT results with them (28% vs. 41%, p = 0.021). CONCLUSION:
      Our study demonstrates that while almost all subjects want to be informed of
      their PFT results, this does not occur in a large number of patients. Many
      subjects are agreeable for their PFT results to be communicated to them by
      clinicians other than doctors. Further research is required to develop an
      efficient method of conveying PFT results that will improve patient satisfaction
      and health outcomes.

PMID- 25950952
TI  - Identification of variants in primary and recurrent glioblastoma using a cancer
      specific gene panel and whole exome sequencing.
AB  - Glioblastoma (GBM) is an aggressive, malignant brain tumor typically resulting in
      death of the patient within one year following diagnosis; and those who survive
      beyond this point usually present with tumor recurrence within two years (5-year
      survival is 5%). The genetic heterogeneity of GBM has made the molecular
      characterization of these tumors an area of great interest and has led to
      identification of molecular subtypes in GBM. The availability of sequencing
      platforms that are both fast and economical can further the adoption of tumor
      sequencing in the clinical environment, potentially leading to identification of
      clinically actionable genetic targets. In this pilot study, comprised of triplet
      samples of normal blood, primary tumor, and recurrent tumor samples from three
      patients; we compared the ability of Illumina whole exome sequencing (ExomeSeq)
      and the Ion AmpliSeq Comprehensive Cancer Panel (CCP) to identify somatic
      variants in patient-paired primary and recurrent tumor samples. Thirteen genes
      were found to harbor variants, the majority of which were exclusive to the
      ExomeSeq data. Surprisingly, only two variants were identified by both platforms
      and they were located within the PTCH1 and NF1 genes. Although preliminary in
      nature, this work highlights major differences in variant identification in data
      generated from the two platforms. Additional studies with larger samples sizes
      are needed to further explore the differences between these technologies and to
      enhance our understanding of the clinical utility of panel based platforms in
      genomic profiling of brain tumors. 

PMID- 25950953
TI  - The meaning of body image experiences during the perinatal period: A systematic
      review of the qualitative literature.
AB  - Literature reporting body image disturbances across the perinatal period has
      produced inconsistent findings, owing to the complexity of body image experiences
      during pregnancy and the first year postpartum. Existing qualitative data might
      provide potential avenues to advance understanding of pregnancy-related body
      image experiences and guide future quantitative research. The present systematic
      review synthesised the findings of 10 qualitative studies exploring the body
      image experiences of women through the perinatal period, albeit the majority
      focused only on pregnancy. Themes emerging included malleability of body image
      ideals across pregnancy (including the shift from aesthetic to functional
      concerns about one's appearance), the salience of stomach and breasts for self
      rated body satisfaction, and perceived pressure to limit weight gain across
      pregnancy in order to return quickly to pre-pregnancy figure following birth.
      These qualitative findings suggest greater complexity of body image experiences
      during perinatal period than can be captured by typically used self-report
      measures. 

PMID- 25950954
TI  - Clinical test to detect mecA and antibiotic resistance in Staphylococcus aureus,
      based on novel biotechnological methods.
AB  - BACKGROUND AND OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA) is
      one of the most common organisms isolated from clinical samples, and has been
      associated with morbidity and mortality among hospitalized patients. The aim of
      this study was to evaluate the prevalence and antibiotic susceptibility patterns
      among MRSA and methicillin-sensitive S. aureus (MSSA) isolates collected from
      four hospitals in Iran. MATERIAL AND METHODS: A total of 183 isolates of S.
      aureus were collected from various clinical specimens of four hospitals in Iran.
      The isolates were identified by using the conventional biochemical tests. Three
      methods-oxacillin agar disk diffusion, oxacillin agar screening, and PCR- were
      applied to determine susceptibility to oxacillin. The conventional disk agar
      diffusion test was used to evaluate the antibiotic sensitivity of our isolates
      against 15 antibiotics, according to the guidelines of the Clinical and
      Laboratory Standards Institute (CLSI). RESULTS: Of 183 isolates, 77 isolates
      (42.1%) were found to be MRSA, by the PCR method. The highest antibiotic
      resistance was found to be against penicillin, co-trimoxazole, erythromycin, and
      tetracycline respectively. All isolates were susceptible to vancomycin, according
      to the results of disk agar diffusion. Among other antibiotics, teicoplanin (84%)
      and fusidic acid (80.5%) were more active against MRSA isolates. For the
      different methods evaluated, the sensitivities and specificities were as follows:
      for disk agar diffusion (84.9% and 95.9%) and for agar screening test with
      oxacillin concentrations of 0.6 MUg/ml (70.8% and 97.4%), 4 MUg/ml (96.1%and
      97.2%) and 6 MUg/ml (96% and 96.3%), respectively. CONCLUSION: The results of our
      study showed that 47% of S. aureus isolates were MRSA. Overall, in this research
      study, resistance to all test antimicrobial agents in MRSA isolates were higher
      than that of MSSA isolates. Our results also revealed that 85% of mecA-positive
      isolates and 15% of mecA-negative isolates were resistant to methicillin; while
      96% of mecA-negative isolates were sensitive to methicillin. Meanwhile 4% of mecA
      positive isolates were also sensitive to methicillin.

PMID- 25950955
TI  - Application of Box-Behnken design to prepare gentamicin-loaded calcium carbonate
      nanoparticles.
AB  - The aim of this research was to prepare and optimize calcium carbonate (CaCO3)
      nanoparticles as carriers for gentamicin sulfate. A chemical precipitation method
      was used to prepare the gentamicin sulfate-loaded CaCO3 nanoparticles. A 3
      factor, 3-level Box-Behnken design was used for the optimization procedure, with
      the molar ratio of CaCl2: Na2CO3 (X1), the concentration of drug (X2), and the
      speed of homogenization (X3) as the independent variables. The particle size and
      entrapment efficiency were considered as response variables. Mathematical
      equations and response surface plots were used, along with the counter plots, to
      relate the dependent and independent variables. The results indicated that the
      speed of homogenization was the main variable contributing to particle size and
      entrapment efficiency. The combined effect of all three independent variables was
      also evaluated. Using the response optimization design, the optimized Xl-X3
      levels were predicted. An optimized formulation was then prepared according to
      these levels, resulting in a particle size of 80.23 nm and an entrapment
      efficiency of 30.80%. It was concluded that the chemical precipitation technique,
      together with the Box-Behnken experimental design methodology, could be
      successfully used to optimize the formulation of drug-incorporated calcium
      carbonate nanoparticles. 

PMID- 25950956
TI  - Sparse and compositionally robust inference of microbial ecological networks.
AB  - 16S ribosomal RNA (rRNA) gene and other environmental sequencing techniques
      provide snapshots of microbial communities, revealing phylogeny and the
      abundances of microbial populations across diverse ecosystems. While changes in
      microbial community structure are demonstrably associated with certain
      environmental conditions (from metabolic and immunological health in mammals to
      ecological stability in soils and oceans), identification of underlying
      mechanisms requires new statistical tools, as these datasets present several
      technical challenges. First, the abundances of microbial operational taxonomic
      units (OTUs) from amplicon-based datasets are compositional. Counts are
      normalized to the total number of counts in the sample. Thus, microbial
      abundances are not independent, and traditional statistical metrics (e.g.,
      correlation) for the detection of OTU-OTU relationships can lead to spurious
      results. Secondly, microbial sequencing-based studies typically measure hundreds
      of OTUs on only tens to hundreds of samples; thus, inference of OTU-OTU
      association networks is severely under-powered, and additional information (or
      assumptions) are required for accurate inference. Here, we present SPIEC-EASI
      (SParse InversE Covariance Estimation for Ecological Association Inference), a
      statistical method for the inference of microbial ecological networks from
      amplicon sequencing datasets that addresses both of these issues. SPIEC-EASI
      combines data transformations developed for compositional data analysis with a
      graphical model inference framework that assumes the underlying ecological
      association network is sparse. To reconstruct the network, SPIEC-EASI relies on
      algorithms for sparse neighborhood and inverse covariance selection. To provide a
      synthetic benchmark in the absence of an experimentally validated gold-standard
      network, SPIEC-EASI is accompanied by a set of computational tools to generate
      OTU count data from a set of diverse underlying network topologies. SPIEC-EASI
      outperforms state-of-the-art methods to recover edges and network properties on
      synthetic data under a variety of scenarios. SPIEC-EASI also reproducibly
      predicts previously unknown microbial associations using data from the American
      Gut project. 

PMID- 25950957
TI  - Multicolor fluorescence-based screening toward structural analysis of
      multiprotein membrane complexes.
AB  - Structures of membrane protein complexes provide a wealth of information on their
      biological function, the interplay among their subunits, and on ligand binding.
      Structural genomics of multiprotein membrane complexes seek to deliver structural
      information ideally of most of these complexes. Models of abundant native
      membrane protein complexes have been proposed from X-ray crystallography or
      single-particle cryo-EM. However, most of the remaining membrane protein
      complexes persist in very low copy numbers per cell and cannot be isolated from
      their native source without tremendous efforts. Therefore, heterologous
      expression systems are continually being developed to overproduce membrane
      protein complexes in various host cells of bacterial or eukaryotic origin. Still,
      only a small fraction of membrane proteins is suitable for structure
      determination due to poor expression levels, misfolding and aggregation, complex
      heterogeneity, imbalanced stoichiometry, and difficulties in solubilization as
      well as stabilization of the complexes. Powerful tools are therefore necessary to
      identify the correct expression host and to validate extraction and purification
      strategies for a given membrane protein complex at the earliest time point. Here,
      we discuss a fluorescence-based screening approach particularly tailored for the
      handy and sensitive analysis of the production and purification process for
      multiprotein membrane complexes. Multicolor fluorescence-detection size-exclusion
      chromatography provides a powerful readout system and allows quantitative
      monitoring of the production of critical single subunits of membrane protein
      complexes. The approach facilitates the tracking of improvements during sample
      optimization for monodispersity, balanced stoichiometry, and stability of
      multisubunit membrane protein complexes. 

PMID- 25950959
TI  - Membrane preparation and solubilization.
AB  - Membrane proteins play an essential role in several biological processes like ion
      transport, signal transduction, and electron transfer to name a few. For
      structural and functional studies of integral membrane proteins, it is critically
      important to isolate proteins from the membrane using biological detergents.
      Detergents disrupt the native lipid components of the native membrane and encase
      the membrane protein in an unnatural environment in aqueous solution. However, a
      particular membrane protein is best solubilized in a specific detergent;
      therefore, screening for the optimal detergent is essential. Apart from keeping
      the membrane protein monodispered in solution, the detergent has to be compatible
      with downstream processes to isolate and characterize a membrane protein. Over
      the past several years, a number of membrane proteins have been successfully
      isolated for structural and functional studies that allowed an outline of general
      strategies for isolating a novel membrane protein of interest. 

PMID- 25950960
TI  - Amphipathic agents for membrane protein study.
AB  - Membrane proteins (MPs) are insoluble in aqueous media as a result of
      incompatibility between the hydrophilic property of the solvent molecules and the
      hydrophobic nature of MP surfaces, normally associated with lipid membranes.
      Amphipathic compounds are necessary for extraction of these macromolecules from
      the native membranes and their maintenance in solution. The amphipathic agents
      surround the hydrophobic segments of MPs, thus serving as a membrane mimetic
      system. Of the available amphipathic agents, detergents are most widely used for
      MP manipulation. However, MPs encapsulated by conventional detergent micelles
      have a tendency to undergo structural degradation, hampering MP advance, and
      necessitating the development of novel detergents with enhanced efficacy for MP
      study. In this chapter, we will introduce both conventional and novel classes of
      detergents and discuss about the chemical structures, design principles, and
      efficacies of these compounds for MP solubilization and stabilization. The
      behaviors of those agents toward MP crystallization will be a primary topic in
      our discussion. This discussion highlights the common features of popular
      conventional/novel detergents essential for successful MP structural study. The
      conclusions reached by this discussion would not only enable MP scientists to
      rationally select a set of detergent candidates among a large number of
      detergents but also provide detergent inventors with useful guidelines in
      designing novel amphipathic systems. 

PMID- 25950958
TI  - A Novel Screening Approach for Optimal and Functional Fusion of T4 Lysozyme in
      GPCRs.
AB  - Determination of high-resolution, three-dimensional structures of transmembrane
      proteins (TMPs) has, in many cases, only been accomplished through the use of
      stabilized variant forms of the proteins being studied. For the important G
      protein-coupled receptor superfamily, this has most often been achieved by
      inserting a stable soluble protein, such as T4 lysozyme (T4L), in an internal
      loop of a receptor. However, creation of such fusion proteins generally results
      in loss of the ability of receptors to activate their cognate cytoplasmic G
      proteins. Furthermore, the criteria for designing fusions that minimally perturb
      receptor structure are not well established. We describe here a method for
      creating a library of receptor variants containing T4L inserted into an internal
      loop at varying positions and as replacements for varying amounts of the original
      receptor sequence. We also describe methods for screening for variants displaying
      maximal expression levels, ligand binding capacity, and signaling function. When
      applied to the yeast alpha-factor receptor, Ste2p, this approach allowed recovery
      of well-expressed receptor variants containing internally fused T4L that retained
      nearly normal signaling function. The approach we describe can be readily adapted
      to creation of stabilized fusions of other TMPs expressed in yeast or other
      expression systems. 

PMID- 25950962
TI  - Solubilization of G protein-coupled receptors: a convenient strategy to explore
      lipid-receptor interaction.
AB  - G protein-coupled receptors (GPCRs) are the largest class of molecules involved
      in signal transduction across cell membranes and are major drug targets. Since
      GPCRs are integral membrane proteins, their structure and function are modulated
      by membrane lipids. In particular, membrane cholesterol is an important lipid in
      the context of GPCR function. Solubilization of integral membrane proteins is a
      process in which the proteins and lipids in native membranes are dissociated in
      the presence of a suitable amphiphilic detergent. Interestingly, solubilization
      offers a convenient approach to monitor lipid-receptor interaction as it results
      in differential extents of lipid solubilization, thereby allowing to assess the
      role of specific lipids on receptor function. In this review, we highlight how
      this solubilization strategy is utilized to decipher novel information about the
      structural stringency of cholesterol necessary for supporting the function of the
      serotonin(1A) receptor. We envision that insight in GPCR-lipid interaction would
      result in better understanding of GPCR function in health and disease.

PMID- 25950961
TI  - Quantification of detergent using colorimetric methods in membrane protein
      crystallography.
AB  - Membrane protein crystallography has the potential to greatly aid our
      understanding of membrane protein biology. Yet, membrane protein crystals remain
      challenging to produce. Although robust methods for the expression and
      purification of membrane proteins continue to be developed, the detergent
      component of membrane protein samples is equally important to crystallization
      efforts. This chapter describes the development of three colorimetric assays for
      the quantitation of detergent in membrane protein samples and provides detailed
      protocols. All of these techniques use small sample volumes and have potential
      applications in crystallography. The application of these techniques in
      crystallization prescreening, detergent concentration modification, and detergent
      exchange experiments is demonstrated. It has been observed that the concentration
      of detergent in a membrane protein sample can be just as important as the protein
      concentration when attempting to reproduce crystallization lead conditions. 

PMID- 25950963
TI  - Overexpression, Isolation, Purification, and Crystallization of NhaA.
AB  - Living cells are critically dependent on processes that regulate intracellular
      pH, Na(+) content, and volume. Na(+)/H(+) antiporters play a primary role in
      these homeostatic mechanisms. They are found in the cytoplasmic and intracellular
      membranes of most organisms from bacteria to humans and have long been human drug
      targets. NhaA, the principal Na(+)/H(+) antiporter in Escherichia coli, plays an
      essential role in homeostasis of Na(+) and H(+). It constitutes a paradigm for
      the study of its numerous prokaryotic homologs and of several human Na(+)/H(+)
      antiporters. The crystal structure of NhaA, determined at pH4, has provided the
      first structural and functional insights into the antiport mechanism and pH
      regulation of an Na(+)/H(+) antiporter. Remarkably, the NhaA structure revealed a
      new and unique fold (the "NhaA fold") that has since been observed in four
      additional bacterial secondary transporters. The NhaA structure has facilitated
      the rational interpretation of mutational data obtained in NhaA, revealing the
      antiporter's functional organization. Nevertheless, the crystal structure is a
      single snapshot, determined at acidic pH, when NhaA is downregulated; NhaA is
      activated at pH6.5 and reaches maximal activity at pH8.5. Therefore, it is
      crucial to crystallize the active conformations of NhaA. Herein, we present a
      procedure for determining the structure of NhaA. 

PMID- 25950964
TI  - Purification, Refolding, and Crystallization of the Outer Membrane Protein OmpG
      from Escherichia coli.
AB  - OmpG is a pore-forming protein from E. coli outer membranes. Unlike the classical
      outer membrane porins, which are trimers, the OmpG channel is a monomeric beta
      barrel made of 14 antiparallel beta-strands with short periplasmic turns and
      longer extracellular loops. The channel activity of OmpG is pH dependent and the
      channel is gated by the extracellular loop L6. At neutral/high pH, the channel is
      open and permeable for substrate molecules with a size up to 900 Da. At acidic
      pH, loop L6 folds across the channel and blocks the pore. The channel blockage at
      acidic pH appears to be triggered by the protonation of a histidine pair on
      neighboring beta-strands, which repel one another, resulting in the rearrangement
      of loop L6 and channel closure. OmpG was purified by refolding from inclusion
      bodies and crystallized in two and three dimensions. Crystallization and analysis
      by electron microscopy and X-ray crystallography revealed the fundamental
      mechanisms essential for the channel activity.

PMID- 25950965
TI  - Biophysical Approaches to the Study of LeuT, a Prokaryotic Homolog of
      Neurotransmitter Sodium Symporters.
AB  - Ion-coupled secondary transport is utilized by multiple integral membrane
      proteins as a means of achieving the thermodynamically unfavorable translocation
      of solute molecules across the lipid bilayer. The chemical nature of these
      molecules is diverse and includes sugars, amino acids, neurotransmitters, and
      other ions. LeuT is a sodium-coupled, nonpolar amino acid symporter and
      eubacterial member of the solute carrier 6 (SLC6) family of Na(+)/Cl(-)-dependent
      neurotransmitter transporters. Eukaryotic counterparts encompass the clinically
      and pharmacologically significant transporters for gamma-aminobutyric acid
      (GABA), glycine, serotonin (5-hydroxytryptamine, 5-HT), dopamine (DA), and
      norepinephrine (NE). Since the crystal structure of LeuT was first solved in
      2005, subsequent crystallographic, binding, flux, and spectroscopic studies,
      complemented with homology modeling and molecular dynamic simulations, have
      allowed this protein to emerge as a remarkable mechanistic paradigm for both the
      SLC6 class as well as several other sequence-unrelated SLCs whose members possess
      astonishingly similar architectures. Despite yielding groundbreaking conceptual
      advances, this vast treasure trove of data has also been the source of
      contentious hypotheses. This chapter will present a historical scientific
      overview of SLC6s; recount how the initial and subsequent LeuT structures were
      solved, describing the insights they each provided; detail the accompanying
      functional techniques, emphasizing how they either supported or refuted the
      static crystallographic data; and assemble these individual findings into a
      mechanism of transport and inhibition. 

PMID- 25950966
TI  - Generation of recombinant antibody fragments for membrane protein
      crystallization.
AB  - Membrane proteins are challenging targets for crystallization and structure
      determination by X-ray crystallography. Hurdles can be overcome by antibody
      mediated crystallization. More than 25 unique structures of membrane
      protein:antibody complexes have already been determined. In the majority of
      cases, hybridoma-derived antibody fragments either in Fab or Fv fragment format
      were employed for these complexes. We will briefly introduce the background and
      current status of the strategy and describe in detail the current protocols of
      well-established methods for the immunization, the selection, and the
      characterization of antibodies, as well as the cloning, the production, and the
      purification of recombinant antibodies useful for structural analysis of membrane
      proteins. 

PMID- 25950967
TI  - Phage display selections for affinity reagents to membrane proteins in nanodiscs.
AB  - Phage display selections generate high-affinity synthetic reagents that can be
      used as tools in structural characterization of membrane proteins. Currently,
      most selection protocols are performed with membrane protein targets in
      detergents. However, there are numerous technical issues associated with this,
      primarily that detergents are poor mimics of the native lipid environment. Here,
      we describe a set of protocols for phage display selection that involves
      reconstituting membrane proteins in nanodiscs, which are small discoidal
      particles consisting of lipids enclosed by membrane scaffold proteins. The
      nanodisc format enabled us to expand the capabilities of competitive and
      subtractive phage display selection steps, and generation of high-quality
      synthetic reagents for membrane proteins in native-like lipid environment. 

PMID- 25950968
TI  - Antibody fragments for stabilization and crystallization of G protein-coupled
      receptors and their signaling complexes.
AB  - G protein-coupled receptors (GPCRs) are one of the key players in extracellular
      signal recognition and their subsequent communications with cellular signaling
      machinery. Crystallization and high-resolution structure determination of GPCRs
      has been one of the major advances in the area of GPCR biology over the last 7-8
      years. There have primarily been three approaches to GPCR crystallization till
      date. These are fusion protein strategy, thermostabilization, and antibody
      fragment-mediated crystallization. Of these, antibody fragment-mediated
      crystallization has not only provided the first breakthrough in structure
      determination of a non-rhodopsin GPCR but it has also assisted in obtaining
      structures of fully active conformations of GPCRs. Antibody fragment approach has
      also been crucial in obtaining structural information on GPCR signaling
      complexes. Here, we highlight the specific examples of GPCR crystal structures
      that have utilized antibody fragments for promoting crystallogenesis and
      structure solution. We also discuss emerging powerful technologies such as the
      nanobody technology and the synthetic phage display libraries in the context of
      GPCR crystallization and underline how these tools are likely to propel key GPCR
      structural studies in future. 

PMID- 25950969
TI  - Conformational analysis of g protein-coupled receptor signaling by
      hydrogen/deuterium exchange mass spectrometry.
AB  - Conformational change and protein-protein interactions are two major mechanisms
      of membrane protein signal transduction, including G protein-coupled receptors
      (GPCRs). Upon agonist binding, GPCRs change conformation, resulting in
      interaction with downstream signaling molecules such as G proteins. To understand
      the precise signaling mechanism, studies have investigated the structural
      mechanism of GPCR signaling using X-ray crystallography, nuclear magnetic
      resonance (NMR), or electron paramagnetic resonance. In addition to these
      techniques, hydrogen/deuterium exchange mass spectrometry (HDX-MS) has recently
      been used in GPCR studies. HDX-MS measures the rate at which peptide amide
      hydrogens exchange with deuterium in the solvent. Exposed or flexible regions
      have higher exchange rates and excluded or ordered regions have lower exchange
      rates. Therefore, HDX-MS is a useful tool for studying protein-protein interfaces
      and conformational changes after protein activation or protein-protein
      interactions. Although HDX-MS does not give high-resolution structures, it
      analyzes protein conformations that are difficult to study with X-ray
      crystallography or NMR. Furthermore, conformational information from HDX-MS can
      help in the crystallization of X-ray crystallography by suggesting highly
      flexible regions. Interactions between GPCRs and downstream signaling molecules
      are not easily analyzed by X-ray crystallography or NMR because of the large size
      of the GPCR-signaling molecule complexes, hydrophobicity, and flexibility of
      GPCRs. HDX-MS could be useful for analyzing the conformational mechanism of GPCR
      signaling. In this chapter, we discuss details of HDX-MS for analyzing GPCRs
      using the beta2AR-G protein complex as a model system. 

PMID- 25950971
TI  - Magic-angle-spinning solid-state NMR of membrane proteins.
AB  - Solid-state NMR spectroscopy (ssNMR) provides increasing possibilities to examine
      membrane proteins in different molecular settings, ranging from synthetic
      bilayers to whole cells. This flexibility often enables ssNMR experiments to be
      directly correlated with membrane protein function. In this contribution, we
      discuss experimental aspects of such studies starting with protein expression and
      labeling, leading to membrane protein isolation or to membrane proteins in a
      cellular environment. We show that optimized procedures can depend on aspects
      such as the achieved levels of expression, the stability of the protein during
      purification or proper refolding. Dealing with native membrane samples, such as
      isolated cellular membranes, can alleviate or entirely remove such biochemical
      challenges. Subsequently, we outline ssNMR experiments that involve the use of
      magic-angle-spinning and can be used to study membrane protein structure and
      their functional aspects. We pay specific attention to spectroscopic issues such
      as sensitivity and spectral resolution. The latter aspect can be controlled using
      a combination of tailored preparation procedures with solid-state NMR experiments
      that simplify the spectral analysis using specific filtering and correlation
      methods. Such approaches have already provided access to obtain structural views
      of membrane proteins and study their function in lipid bilayers. Ongoing
      developments in sample preparation and NMR methodology, in particular in using
      hyperpolarization or proton-detection schemes, offer additional opportunities to
      study membrane proteins close to their cellular function. These considerations
      suggest a further increase in the potential of using solid-state NMR in the
      context of prokaryotic or eukaryotic membrane protein systems in the near future.

PMID- 25950972
TI  - Solution NMR Structure Determination of Polytopic alpha-Helical Membrane
      Proteins: A Guide to Spin Label Paramagnetic Relaxation Enhancement Restraints.
AB  - Solution nuclear magnetic resonance structures of polytopic alpha-helical
      membrane proteins require additional restraints beyond the traditional Nuclear
      Overhauser Effect (NOE) restraints. Several methods have been developed and this
      review focuses on paramagnetic relaxation enhancement (PRE). Important aspects of
      spin labeling, PRE measurements, structure calculations, and structural quality
      are discussed. 

PMID- 25950970
TI  - EPR Studies of Gating Mechanisms in Ion Channels.
AB  - Ion channels open and close in response to diverse stimuli, and the molecular
      events underlying these processes are extensively modulated by ligands of both
      endogenous and exogenous origin. In the past decade, high-resolution structures
      of several channel types have been solved, providing unprecedented details of the
      molecular architecture of these membrane proteins. Intrinsic conformational
      flexibility of ion channels critically governs their functions. However, the
      dynamics underlying gating mechanisms and modulations are obscured in the
      information from crystal structures. While nuclear magnetic resonance
      spectroscopic methods allow direct measurements of protein dynamics, they are
      limited by the large size of these membrane protein assemblies in detergent
      micelles or lipid membranes. Electron paramagnetic resonance (EPR) spectroscopy
      has emerged as a key biophysical tool to characterize structural dynamics of ion
      channels and to determine stimulus-driven conformational transition between
      functional states in a physiological environment. This review will provide an
      overview of the recent advances in the field of voltage- and ligand-gated
      channels and highlight some of the challenges and controversies surrounding the
      structural information available. It will discuss general methods used in site
      directed spin labeling and EPR spectroscopy and illustrate how findings from
      these studies have narrowed the gap between high-resolution structures and gating
      mechanisms in membranes, and have thereby helped reconcile seemingly disparate
      models of ion channel function. 

PMID- 25950973
TI  - Inducing two-dimensional crystallization of membrane proteins by dialysis for
      electron crystallography.
AB  - Electron crystallography is an electron cryo-microscopy (cryo-EM) method that is
      particularly suitable for structure-function studies of small membrane proteins,
      which are crystallized in two-dimensional (2D) arrays for subsequent cryo-EM data
      collection and image processing. This approach allows for structural analysis of
      membrane proteins in a close-to-native, phospholipid bilayer environment. The
      process of growing 2D crystals from purified membrane proteins by dialysis
      detergent removal is described in this chapter. A short section covers screening
      for and identifying 2D crystals by transmission electron microscopy, and in the
      last section, optimization of the purification to obtain crystals of higher
      quality is discussed. 

PMID- 25950975
TI  - Bicelles coming of age: an empirical approach to bicelle crystallization.
AB  - Biological membranes represent a unique environment in which integral membrane
      proteins (MPs) fold to perform diverse biological functions. In many cases,
      lipids support the native conformation or mediate important interactions between
      MPs. It is therefore imperative to develop methods that maintain this support for
      the structural and functional analyses of an exceedingly important class of
      biological macromolecules. Bicelles are detergent-stabilized phospholipid bilayer
      discs into which MPs can be reconstituted for biophysical studies. Here, we
      review recent advances and emerging concepts in employing bicelles for the
      crystallization and structure determination of MPs. We discuss variations of
      established procedures as well as alternative approaches, and we present a
      summary and analysis of the conditions used for bicelle-mediated MP
      crystallization. 

PMID- 25950976
TI  - Fluorescence Recovery After Photobleaching in Lipidic Cubic Phase (LCP-FRAP): A
      Precrystallization Assay for Membrane Proteins.
AB  - Crystallization of integral membrane proteins (MPs) is notoriously difficult,
      given their poor stability outside native membrane environment and due to the
      interference of detergent micelles with crystallization process. MP
      crystallization in a membrane mimetic matrix, known as lipidic cubic phase (LCP),
      has recently started to gain popularity, following successes in structure
      determination of G protein-coupled receptors (GPCRs), transporters, and enzymes.
      Unlike crystallization trials in aqueous solutions where protein molecules are
      free to move, diffusion of MPs in LCP is restricted, and, thus, a high level of
      protein mobility can serve as an early indication for subsequent crystallization
      success. Prompted by our initial observations that precipitant conditions can
      dramatically affect diffusion of GPCRs in LCP, we have developed a simple
      precrystallization assay, based on measuring protein diffusion at a number of
      different conditions by fluorescence recovery after photobleaching (LCP-FRAP).
      Over the last few years, the LCP-FRAP assay was incorporated in our GPCR
      structure determination pipeline and proved as a powerful technique allowing for
      a faster identification of crystallization conditions for many different
      receptors. The assay is used to screen for the best protein constructs, ligands,
      LCP host lipids, precipitants, and additives, thereby focusing subsequent
      crystallization trials on the most promising parts of the multidimensional
      crystallization phase diagram, substantially increasing the likelihood of finding
      the right crystallization condition. Here, we describe our LCP-FRAP protocols for
      guiding GPCR crystallization, which can be adapted to any other MP, and discuss
      some of the critical considerations related to application of this assay. 

PMID- 25950974
TI  - Crystallization of membrane proteins by vapor diffusion.
AB  - X-ray crystallography remains the most robust method to determine protein
      structure at the atomic level. However, the bottlenecks of protein expression and
      purification often discourage further study. In this chapter, we address the most
      common problems encountered at these stages. Based on our experiences in
      expressing and purifying antimicrobial efflux proteins, we explain how a pure and
      homogenous protein sample can be successfully crystallized by the vapor diffusion
      method. We present our current protocols and methodologies for this technique.
      Case studies show step-by-step how we have overcome problems related to
      expression and diffraction, eventually producing high-quality membrane protein
      crystals for structural determinations. It is our hope that a rational approach
      can be made of the often anecdotal process of membrane protein crystallization. 

PMID- 25950977
TI  - Crystallization of proteins from crude bovine rod outer segments.
AB  - Obtaining protein crystals suitable for X-ray diffraction studies comprises the
      greatest challenge in the determination of protein crystal structures, especially
      for membrane proteins and protein complexes. Although high purity has been
      broadly accepted as one of the most significant requirements for protein
      crystallization, a recent study of the Escherichia coli proteome showed that many
      proteins have an inherent propensity to crystallize and do not require a highly
      homogeneous sample (Totir et al., 2012). As exemplified by RPE65 (Kiser, Golczak,
      Lodowski, Chance, & Palczewski, 2009), there also are cases of mammalian proteins
      crystallized from less purified samples. To test whether this phenomenon can be
      applied more broadly to the study of proteins from higher organisms, we
      investigated the protein crystallization profile of bovine rod outer segment
      (ROS) crude extracts. Interestingly, multiple protein crystals readily formed
      from such extracts, some of them diffracting to high resolution that allowed
      structural determination. A total of seven proteins were crystallized, one of
      which was a membrane protein. Successful crystallization of proteins from
      heterogeneous ROS extracts demonstrates that many mammalian proteins also have an
      intrinsic propensity to crystallize from complex biological mixtures. By
      providing an alternative approach to heterologous expression to achieve
      crystallization, this strategy could be useful for proteins and complexes that
      are difficult to purify or obtain by recombinant techniques. 

PMID- 25950979
TI  - Major intrinsic protein superfamily: channels with unique structural features and
      diverse selectivity filters.
AB  - Members of the superfamily of major intrinsic proteins (MIPs) facilitate water
      and solute permeability across cell membranes and are found in sources ranging
      from bacteria to humans. Aquaporin and aquaglyceroporin channels are the
      prominent members of the MIP superfamily. Experimental studies show that MIPs are
      involved in important physiological processes in mammals and plants. They are
      implicated in several human diseases and are considered to be attractive drug
      targets for a wide range of diseases such as cancer, brain edema, epilepsy,
      glaucoma, and congestive heart failure. Three-dimensional structures of MIP
      channels from diverse sources reveal that MIPs adopt a unique conserved hourglass
      helical fold consisting of six transmembrane helices (TM1-TM6) and two half
      helices (LB and LE). Conserved NPA motifs near the center and the
      aromatic/arginine selectivity filter (Ar/R SF) toward the extracellular side
      constitute two narrow constriction regions within the channel. Structural
      knowledge combined with simulation studies have helped to investigate the role of
      these two constriction regions in the transport and selectivity of the solutes.
      With the availability of many genome sequences from diverse species, a large
      number of MIP genes have been identified. Homology models of 1500 MIP channels
      have been used to derive structure-based sequence alignment of TM1-TM6 helices
      and the two half-helices LB and LE. Thirteen residues are highly conserved in
      different transmembrane helices and half-helices. High group conservation of
      small and weakly polar residues is observed in 27 positions at the interface of
      two interacting helices. Thus, although the MIP sequences are diverse, the
      hourglass helical fold is maintained during evolution with the conservation of
      these 40 positions within the transmembrane region. We have proposed a generic
      structure-based numbering scheme for the MIP channels that will facilitate easier
      comparison of the MIP sequences. Analysis of Ar/R SF in all 1500 MIPs indicates
      the extent of diversity in the four residues that form this narrow region.
      Certain residues are completely avoided in the SF, even if they have the same
      chemical nature as that of the most frequently observed residues. For example,
      arginine is the most preferred residue in a specific position of Ar/R SF, whereas
      lysine is almost always avoided in any of the four positions. MIP channels with
      highly hydrophobic or hydrophilic Ar/R SF have been identified. Similarly, there
      are examples of MIP channels in which all four residues of Ar/R SF are bulky,
      thus almost occluding the pore. Many plant MIPs possess small residues at all SF
      positions, resulting in a larger pore diameter. A majority of MIP channels are
      yet to be functionally characterized, and their in vivo substrates are not yet
      identified. A complete understanding of the relationship between the nature of
      Ar/R SF and the solutes that are transported is required to exploit MIP channels
      as potential drug targets. 

PMID- 25950978
TI  - Crystallization of Photosystem II for Time-Resolved Structural Studies Using an X
      ray Free Electron Laser.
AB  - Photosystem II (PSII) is a membrane protein supercomplex that executes the
      initial reaction of photosynthesis in higher plants, algae, and cyanobacteria. It
      captures the light from the sun to catalyze a transmembrane charge separation. In
      a series of four charge separation events, utilizing the energy from four
      photons, PSII oxidizes two water molecules to obtain dioxygen, four protons, and
      four electrons. The light reactions of photosystems I and II (PSI and PSII)
      result in the formation of an electrochemical transmembrane proton gradient that
      is used for the production of ATP. Electrons that are subsequently transferred
      from PSI via the soluble protein ferredoxin to ferredoxin-NADP(+) reductase that
      reduces NADP(+) to NADPH. The products of photosynthesis and the elemental oxygen
      evolved sustain all higher life on Earth. All oxygen in the atmosphere is
      produced by the oxygen-evolving complex in PSII, a process that changed our
      planet from an anoxygenic to an oxygenic atmosphere 2.5 billion years ago. In
      this chapter, we provide recent insight into the mechanisms of this process and
      methods used in probing this question. 

PMID- 25950980
TI  - Comparative Sequence-Function Analysis of the Major Facilitator Superfamily: The
      "Mix-and-Match" Method.
AB  - The major facilitator superfamily (MFS) is a diverse group of secondary
      transporters with members found in all kingdoms of life. The paradigm for MFS is
      the lactose permease (LacY) of Escherichia coli, which has been the test bed for
      the development of many methods applied for the analysis of transport proteins. X
      ray structures of an inward-facing conformation and the most recent structure of
      an almost occluded conformation confirm many conclusions from previous studies.
      One fundamentally important problem for understanding the mechanism of secondary
      active transport is the identification and physical localization of residues
      involved in substrate and H(+) binding. This information is exceptionally
      difficult to obtain with the MFS because of the broad sequence diversity among
      the members. The increasing number of solved MFS structures has led to the
      recognition of a common feature: inverted structure-repeat, formed by fused
      triple-helix domains with opposite orientation in the membrane. The presented
      method here exploits this feature to predict functionally homologous positions of
      known relevant positions in LacY. The triple-helix motifs are aligned in
      combinatorial fashion so as to detect substrate and H(+)-binding sites in
      symporters that transport substrates, ranging from simple ions like phosphate to
      more complex disaccharides. 

PMID- 25950981
TI  - Elucidating Ligand-Modulated Conformational Landscape of GPCRs Using Cloud
      Computing Approaches.
AB  - G-protein-coupled receptors (GPCRs) are a versatile family of membrane-bound
      signaling proteins. Despite the recent successes in obtaining crystal structures
      of GPCRs, much needs to be learned about the conformational changes associated
      with their activation. Furthermore, the mechanism by which ligands modulate the
      activation of GPCRs has remained elusive. Molecular simulations provide a way of
      obtaining detailed an atomistic description of GPCR activation dynamics. However,
      simulating GPCR activation is challenging due to the long timescales involved and
      the associated challenge of gaining insights from the "Big" simulation datasets.
      Here, we demonstrate how cloud-computing approaches have been used to tackle
      these challenges and obtain insights into the activation mechanism of GPCRs. In
      particular, we review the use of Markov state model (MSM)-based sampling
      algorithms for sampling milliseconds of dynamics of a major drug target, the G
      protein-coupled receptor beta2-AR. MSMs of agonist and inverse agonist-bound
      beta2-AR reveal multiple activation pathways and how ligands function via
      modulation of the ensemble of activation pathways. We target this ensemble of
      conformations with computer-aided drug design approaches, with the goal of
      designing drugs that interact more closely with diverse receptor states, for
      overall increased efficacy and specificity. We conclude by discussing how cloud
      based approaches present a powerful and broadly available tool for studying the
      complex biological systems routinely. 

PMID- 25950982
TI  - Membrane proteins--engineering, purification and crystallization. Preface.

PMID- 25950983
TI  - microRNA-21 expression is elevated in esophageal adenocarcinoma after neoadjuvant
      chemotherapy.
AB  - We investigated whether microRNA-21 and microRNA-148a are predictive for
      neoadjuvant treatment in esophageal adenocarcinoma. Thirty-six patients with
      neoadjuvant therapy and surgical resection were included. FFPE tissue from biopsy
      and esophagectomy were analyzed using RT-qPCR. Results were correlated to
      histological tumor regression, histopathological variables, FDG-PET-CT and
      survival. MicroRNA-21 was significantly higher in esophagectomies than in
      corresponding biopsies (p = .027). No association of microRNA-21 or microRNA-148a
      expression in tissue specimens with other clinical parameters was present.
      Although no influence of microRNA-21 and microRNA-148a on the response to
      neoadjuvant therapy was seen, upregulation of microRNA-21 might represent an
      escape mechanism of tumor cells. 

PMID- 25950984
TI  - Strong Hall-Petch Type Behavior in the Elastic Strain Limit of Nanotwinned Gold
      Nanowires.
AB  - Pushing the limits of elastic deformation in nanowires subjected to stress is
      important for the design and performance of nanoscale devices from elastic strain
      engineering. Particularly, introducing nanoscale twins has proved effective in
      rising the tensile strength of metals. However, attaining ideal elastic strains
      in nanotwinned materials remains challenging, because nonuniform twin sizes
      locally affect the yielding behavior. Here, using in situ high-resolution
      transmission electron microscopy tensile testing of nanotwinned [111]-oriented
      gold nanowires, we report direct lattice-strain measurements that demonstrate a
      strong Hall-Petch type relationship in the elastic strain limit up to 5.3%, or
      near the ideal theoretical limit, as the twin size is decreased below 3 nm. It is
      found that the largest twin in nanowires with irregular twin sizes controls the
      slip nucleation and yielding processes in pure tension, which is in agreement
      with earlier atomistic simulations. Continuous hardening behavior without loss of
      strength or softening is observed in nanotwinned single-crystalline gold
      nanowires, which differs from the behaviors of bulk nanocrystalline and
      nanotwinned-nanocrystalline metals. These findings are of practical value for the
      use of nanotwinned metallic and semiconductor nanowires in strain-engineered
      functional microdevices. 

PMID- 25950985
TI  - Sample-free quantification of blood biomarkers via laser-treated skin.
AB  - Surface modified microneedle (MN) arrays are being developed to capture
      circulating biomarkers from the skin, but inefficiency and unreliability of the
      current method limit its clinical applications. We describe here that
      illumination of a tiny area of the skin with hemoglobin-preferably absorbent
      laser increased the amount of circulating biomarkers in the upper dermis by more
      than 1000-fold. The hemoglobin-specific light altered the permeability of
      capillaries leading to extravasation of molecules but not blood cells beneath the
      skin involved. When specific probe-coated MN arrays were applied into the laser
      treated skin, the biomarkers accumulated in the upper dermis were reliably,
      accurately, and sufficiently captured as early as 15 min of the assay. The
      maximal binding occurred in 1 h in a manner independent of penetration depth or a
      molecular mass of the biomarker. With anti-fluorescein isothiocyanate (FITC)-MNs,
      we were able to measure blood concentrations of FITC in mice receiving FITC
      intravenously. The sensitivity and accuracy were comparable to those attained by
      fluorescence spectrophotometer. Likewise, MNs containing influenza hemagglutinin
      (HA) could detect anti-HA antibody in mice or swine receiving influenza vaccines
      as effectively as standard immunoassays. The novel, minimally invasive approach
      holds great promise for measurement of multiple biomarkers by a single array for
      point-of-care diagnosis.

PMID- 25950987
TI  - Polychlorinated biphenyl quinone induces endoplasmic reticulum stress, unfolded
      protein response, and calcium release.
AB  - Organisms are able to respond to environmental insult to maintain cellular
      homeostasis, which include the activation of a wide range of cellular adaptive
      responses with tightly controlled mechanisms. The endoplasmic reticulum (ER) is
      an organelle responsible for protein folding and calcium storage. ER stress leads
      to the accumulation of unfolded proteins in the ER lumen. To be against or
      respond to this effect, cells have a comprehensive signaling system, called
      unfolded protein response (UPR), to restore homeostasis and normal ER function or
      activate the cell death program. Therefore, it is critical to understand how
      environmental insult regulates the ingredients of ER stress and UPR signalings.
      Previously, we have demonstrated that polychlorinated biphenyl (PCB) quinone
      caused oxidative stress, cytotoxicity, genotoxicity, and apoptosis in HepG2
      cells. Here, we investigated the role of a PCB quinone, PCB29-pQ on ER stress,
      UPR, and calcium release. PCB29-pQ markedly increased the hallmark genes of ER
      stress, namely, glucose-regulated protein 78 (GRP78), GRP94, and C/EBP homologous
      protein (CHOP) on both protein and mRNA levels in HepG2 cells. We also confirmed
      PCB29-pQ induced ER morphological defects by using transmission electron
      microscopy. Moreover, PCB29-pQ induced intracellular calcium accumulation and
      calpain activity, which were significantly inhibited by the pretreatment of BAPTA
      AM (Ca(2+) chelator). These results were correlated with the outcome that PCB29
      pQ induces ER stress-related apoptosis through caspase family gene 12, while
      salubrinal and Z-ATAD-FMK (a specific inhibitor of caspase 12) partially
      ameliorated this effect, respectively. N-Acetyl-l-cysteine (NAC) scavenged ROS
      formation and consequently alleviated PCB29-pQ-induced expression of ER stress
      related genes. In conclusion, our result demonstrated for the first time that PCB
      quinone leads to ROS-dependent induction of ER stress, and UPR and calcium
      release in HepG2 cells, and the evaluation of the perturbations of ER stress,
      UPR, and calcium signaling provide further information on the mechanisms of PCB
      induced toxicity.

PMID- 25950988
TI  - Vesicles on the breast post-mastectomy: a quiz -- lymphangioma circumscriptum.

PMID- 25950989
TI  - Which patients with ARDS benefit from lung biopsy?
AB  - A central tenet of caring for patients with ARDS is to treat the underlying
      cause, be it sepsis, pneumonia, or removal of an offending toxin. Identifying the
      risk factor for ARDS has even been proposed as essential to diagnosing ARDS. Not
      infrequently, however, the precipitant for acute hypoxemic respiratory failure is
      unclear, and this raises the question of whether a histologic lung diagnosis
      would benefit the patient. In this review, we consider the historic role of
      pathology in establishing a diagnosis of ARDS and the published experience of
      surgical and transbronchial lung biopsy in patients with ARDS. We reflect on
      which pathologic diagnoses influence treatment and suggest a patient-centric
      approach to weigh the risks and benefits of a lung biopsy for critically ill
      patients who may have ARDS. 

PMID- 25950990
TI  - Oncologic and Functional Outcomes of Surgical and Nonsurgical Treatment of
      Advanced Squamous Cell Carcinoma of the Supraglottic Larynx.
AB  - IMPORTANCE: Nonsurgical treatment of advanced supraglottic laryngeal cancer is
      widely used as part of a larynx preservation protocol. However, recent studies
      have suggested that nonsurgical treatment may be associated with inferior
      survival. Furthermore, it is not clear whether preservation of the larynx
      provides superior voice or swallowing function in the long term. OBJECTIVE: To
      test the hypothesis that surgical treatment of advanced-stage squamous cell
      carcinoma of the supraglottic larynx is associated with superior overall survival
      (OS), freedom from recurrence (FFR), and noninferior voice and swallowing
      function. DESIGN, SETTING, AND PARTICIPANTS: Retrospective medical record review
      of patients treated for stage III or IV squamous cell carcinoma of the
      supraglottic larynx between January 1990 and June 2013 at a tertiary referral
      center: 97 patients underwent surgical treatment and 138, nonsurgical treatment.
      Exclusion criteria included prior definitive treatment for laryngeal cancer or
      evidence of distant metastatic disease at presentation. The median follow-up for
      all 235 patients was 63 months. INTERVENTIONS: Surgical or nonsurgical therapy.
      MAIN OUTCOMES AND MEASURES: Freedom from recurrence (FFR), OS, larynx
      preservation, voice graded from 1 to 5, and swallowing graded from 1 to 6 using
      our voice and swallowing function scales. RESULTS: Surgical treatment was
      associated with superior FFR (5-year FFR: 75% vs 55%; P = .006) but not OS (5
      year OS: 52% vs 52%; P = .61). The larynx was preserved in 83% of patients in the
      nonsurgical group vs 42% of patients in the surgical group (P < .001). Voice
      function was superior in the nonsurgical group at all time points through 5 years
      after treatment (mean voice score, 3.8 vs 2.6; P < .001). Swallowing function was
      comparable between surgical and nonsurgical groups. Multivariable analysis
      revealed that advanced age (hazard ratio [HR], 1.43 per 10-year increment; 95%
      CI, 1.19-1.72) and clinical N stage (HR, 1.17 per 1-level increment; 95% CI, 1.05
      1.30) were associated with worse OS, while treatment with chemotherapy was
      associated with superior OS (HR, 0.61; 95% CI, 0.41-0.92). CONCLUSIONS AND
      RELEVANCE: Compared with surgical treatment, nonsurgical treatment as part of a
      larynx preservation protocol is associated with a higher likelihood of recurrence
      but has similar OS and should continue to be viewed as a viable alternative for
      the treatment of advanced supraglottic laryngeal cancer.

PMID- 25950991
TI  - Combined MCD/DFT/TDDFT Study of the Electronic Structure of Axially Pyridine
      Coordinated Metallocorroles.
AB  - A series of metallocorroles were investigated by UV-vis and magnetic circular
      dichroism spectroscopies. The diamagnetic distorted square-pyramidal main-group
      corrole Ga(tpfc)py (2), the diamagnetic distorted octahedral transition-metal
      adduct Co(tpfc)(py)2 (3), and paramagnetic distorted octahedral transition-metal
      complex Fe(tpfc)(py)2 (4) [H3tpfc = tris(perfluorophenyl)corrole] were studied to
      investigate similarities and differences in the electronic structure and
      spectroscopy of the closed- and open-shell metallocorroles. Similar to the free
      base H3tpfc (1), inspection of the MCD Faraday B-terms for all of the macrocycles
      presented in this report revealed that a DeltaHOMO < DeltaLUMO [DeltaHOMO is the
      energy difference between two highest energy corrole-centered pi-orbitals and
      DeltaLUMO is the energy difference between two lowest energy corrole-centered pi*
      orbitals originating from ML +/- 4 and ML +/- 5 pairs of perimeter] condition is
      present for each complex, which results in an unusual sign-reversed sequence for
      pi-pi* transitions in their MCD spectra. In addition, the MCD spectra of the
      cobalt and the iron complexes were also complicated by a number of charge
      transfer states in the visible region. Iron complex 4 also exhibits a low-energy
      absorption in the NIR region (1023 nm). DFT and TDDFT calculations were used to
      elaborate the electronic structures and provide band assignments in UV-vis and
      MCD spectra of the metallocorroles. DFT and TDDFT calculations predict that the
      orientation of the axial pyridine ligand(s) has a very minor influence on the
      calculated electronic structures and absorption spectra in the target systems. 

PMID- 25950992
TI  - Evaluation of the Alere NT-proBNP Test for Point of Care Testing.
AB  - BACKGROUND: The object of the study was to evaluate the Alere point of care NT
      proBNP assay as a suitable alternative to the central laboratory method to
      provide short test turnaround times in primary care. METHOD: Blood NT-proBNP
      results obtained with the Alere assay (n = 100) were compared with serum NT
      proBNP results analyzed by a Cobas 8000 analyzer (Roche Diagnostics, Mannheim,
      Germany). RESULTS: There was a good agreement between the two NT-proBNP methods
      when used as a rule-out test for heart failure (HF) and the cut-off value <300
      ng/l. A total of 47 samples gave values <300 ng/L with both methods and 51
      samples gave values >300 with both methods. Thus, there was an agreement for 98%
      of the samples. CONCLUSIONS: The study shows that the Alere NT-proBNP assay could
      be used in primary care permitting rapid NT-proBNP testing to rule out HF.

PMID- 25950993
TI  - Detecting pleiotropy in Mendelian randomisation studies with summary data and a
      continuous outcome.
AB  - Mendelian randomisation (MR) estimates causal effects of modifiable phenotypes on
      an outcome by using genetic variants as instrumental variables, but its validity
      relies on the assumption of no pleiotropy, that is, genes influence the outcome
      only through the given phenotype. Excluding pleiotropy is difficult, but the use
      of multiple instruments can indirectly address the issue: if all genes represent
      valid instruments, their MR estimates should vary only by chance. The Sargan test
      detects pleiotropy when individual phenotype, outcome and genotype data are
      measured in the same subjects. We propose an alternative approach to be used when
      only summary genetic data are available or data on gene-phenotype and gene
      outcome come from different subjects. The presence of pleiotropy is investigated
      using the between-instrument heterogeneity Q test (together with the I(2) index)
      in a meta-analysis of MR Wald estimates, derived separately from each instrument.
      For a continuous outcome, we evaluate the approach through simulations and
      illustrate it using published data. For the scenario where all data come from the
      same subjects, we compare it with the Sargan test. The Q test tends to be
      conservative in small samples. Its power increases with the degree of pleiotropy
      and the sample size, as does the precision of the I(2) index, in which case
      results are similar to those of the Sargan test. In MR studies with large sample
      sizes based on summary data, the between-instrument Q test represents a useful
      tool to explore the presence of heterogeneity due to pleiotropy or other causes.

PMID- 25950994
TI  - Nanoparticles as Nonfluorescent Analogues of Fluorophores for Optical Nanoscopy.
AB  - Optical microscopy modalities that achieve spatial resolution beyond the
      resolution limit have opened up new opportunities in the biomedical sciences to
      reveal the structure and kinetics of biological processes on the nanoscale. These
      methods are, however, mostly restricted to fluorescence as contrast mechanism,
      which limits the ultimate spatial resolution and observation time that can be
      achieved by photobleaching of the fluorescent probes. Here, we demonstrate that
      Raman scattering provides a valuable contrast mechanism for optical nanoscopy in
      the form of super-resolution structured illumination microscopy. We find that
      nanotags, i.e., gold and silver nanoparticles that are capable of surface
      enhanced Raman scattering (SERS), can be imaged with a spatial resolution beyond
      the diffraction limit in four dimensions alongside and with similar excitation
      power as fluorescent probes. The highly polarized nature of super-resolution
      structured illumination microscopy renders these nanotags elliptical in the
      reconstructed super-resolved images, which enables us to determine their
      orientation within the sample. The robustness of nanotags against photobleaching
      allows us to image these particles for unlimited periods of time. We demonstrate
      this by imaging isolated nanotags in a dense layer of fluorophores, as well as on
      the surface of and after internalization by osteosarcoma cells, always in the
      presence of fluorescent probes. Our results show that SERS nanotags have the
      potential to become highly multiplexed and chemically sensitive optical probes
      for optical nanoscopy that can replace fluorophores in applications where
      fluorescence photobleaching is prohibitive for following the evolution of
      biological processes for extended times. 

PMID- 25950995
TI  - Medical therapy vs surgery for recurrent acute rhinosinusitis.
AB  - BACKGROUND: Treatment indications for recurrent acute rhinosinusitis (RARS)
      remain poorly defined. We studied outcomes of medical vs surgical treatment of
      RARS, anatomic variants associated with RARS, and factors predicting crossover
      from medical to surgical treatment. METHODS: A total of 220 RARS patients treated
      between 2006 and 2014 were retrospectively divided into 3 cohorts: medical only
      (MED); surgical only (SURG); or medical crossing over into surgical (CROSS).
      Twenty-two item Sino-Nasal Outcome Test (SNOT-22) scores, modified Lund-Kennedy
      endoscopy scores, and prevalence of anatomic variants by computed tomography (CT)
      were compared. A total of 220 CT scans obtained for non-sinus indications served
      as controls. A logistic regression model was used for analysis. RESULTS: The mean
      baseline SNOT-22 scores for all cohorts were similar (MED = 48, SURG = 49, CROSS
      = 45, p < 0.0001). The SURG cohort showed greater reduction of SNOT-22 scores
      compared to the MED cohort at 3, 6, and 12 months follow-up (p < 0.0001). The
      crossover cohort converted to surgery after escalation of SNOT-22 score by a mean
      of 15 points (p < 0.03), and showed significant reduction postoperatively (p <
      0.0001). Haller cell (odds ratio [OR] 3.9; p < 0.0001), concha bullosa (OR 3.7; p
      < 0.003), and accessory ostium (OR 2.2; p < 0.01) were more common in the entire
      RARS group vs controls; however, there were no inter-cohort differences in
      prevalence. CONCLUSION: RARS patients can benefit from both medical and surgical
      treatment strategies, but surgical treatment results in greater symptomatic
      improvement compared to medical treatment. Patients cross over from medical to
      surgical treatment when SNOT-22 scores escalate by a mean of 15 points. Haller
      cell, concha bullosa, and accessory ostium are associated with RARS but are
      equally common in medical, surgical, and crossover cohorts.

PMID- 25950997
TI  - Surgical treatment for portal hypertension.

PMID- 25950996
TI  - Proteomic analysis of secreted proteins by human bronchial epithelial cells in
      response to cadmium toxicity.
AB  - For years, many studies have been conducted to investigate the intracellular
      response of cells challenged with toxic metal(s), yet, the corresponding
      secretome responses, especially in human lung cells, are largely unexplored.
      Here, we provide a secretome analysis of human bronchial epithelial cells (BEAS
      2B) treated with cadmium chloride (CdCl2 ), with the aim of identifying secreted
      proteins in response to Cd toxicity. Proteins from control and spent media were
      separated by two-dimensional electrophoresis and visualized by silver staining.
      Differentially-secreted proteins were identified by MALDI-TOF-MS analysis and
      database searching. We characterized, for the first time, the extracellular
      proteome changes of BEAS-2B dosed with Cd. Our results unveiled that Cd treatment
      led to the marked upregulation of molecular chaperones, antioxidant enzymes,
      enzymes associated with glutathione metabolic process, proteins involved in
      cellular energy metabolism, as well as tumor-suppressors. Pretreatment of cells
      with the thiol antioxidant glutathione before Cd treatment effectively abrogated
      the secretion of these proteins and prevented cell death. Taken together, our
      results demonstrate that Cd causes oxidative stress-induced cytotoxicity; and the
      differentially-secreted protein signatures could be considered as targets for
      potential use as extracellular biomarkers upon Cd exposure. 

PMID- 25950998
TI  - Protein kinetics in human endotoxaemia and their temporal relation to metabolic,
      endocrine and proinflammatory cytokine responses.
AB  - BACKGROUND: Sepsis is associated with profound alterations in protein metabolism.
      The unpredictable time course of sepsis and the multiplicity of confounding
      factors prevent studies of temporal relations between the onset of endocrine and
      proinflammatory cytokine responses and the onset of protein catabolism. This
      study aimed to determine the time course of whole-body protein catabolism, and
      relate it to the endocrine, metabolic and cytokine responses in a human
      endotoxaemia model of early sepsis. METHODS: Six healthy male volunteers were
      studied twice in random order, before and for 600 min after administration of
      either an intravenous bolus of Escherichia coli lipopolysaccharide (LPS) or
      sterile saline. Whole-body protein synthesis, breakdown and net protein breakdown
      were measured by amino acid tracer infusion, and related to changes in plasma
      levels of growth hormone, glucagon, cortisol, insulin-like growth factor (IGF) 1,
      tumour necrosis factor (TNF) alpha and interleukin (IL) 6. RESULTS: Protein
      synthesis, breakdown and net protein breakdown increased and peaked 120 min after
      LPS administration (P < 0.001), the alterations persisting for up to 480 min.
      These peaks coincided with peaks in plasma growth hormone, TNF-alpha and IL-6
      concentrations (P = 0.049, P < 0.001 and P < 0.001 for LPS versus saline),
      whereas plasma cortisol concentration peaked later. No alterations in plasma
      insulin or glucagon concentrations, or in the IGF axis were observed during the
      period of abnormalities of protein metabolism. CONCLUSION: LPS administration
      induced an early protein catabolic response in young men and this coincided with
      changes in plasma growth hormone, TNF-alpha and IL-6 concentrations, rather than
      changes in cortisol, glucagon, insulin or the IGF axis. Surgical relevance Sepsis
      in surgical patients is common and remains associated with substantial mortality.
      Although sepsis is a heterogeneous condition and its pathophysiology therefore
      difficult to study, a universal and profound clinical problem is protein
      catabolism not responsive to nutritional support. Human experimental endotoxaemia
      is a promising model of clinical sepsis that can be used to elucidate underlying
      pathophysiology and explore novel therapeutic approaches. This study demonstrates
      that human experimental endotoxaemia replicates the changes in whole-body protein
      turnover seen in clinical sepsis. Frequent measurements allowed identification of
      tumour necrosis factor (TNF) alpha, interleukin (IL) 6 and growth hormone as
      putative mediators. Human experimental endotoxaemia is a valid model for further
      study of mechanisms and putative therapies of catabolism associated with sepsis.
      In particular, effects of TNF-alpha and IL-6 blockade should be evaluated.

PMID- 25951001
TI  - Chemical Characterization and Anti-Oomycete Activity of Laureliopsis philippianna
      Essential Oils against Saprolegnia parasitica and S. australis.
AB  - Laureliopsis philippiana (Looser) R. Schodde (Monimiaceae) is a native tree
      widespread in the forest areas in the south of Chile and Argentina, known for its
      medicinal properties and excellent wood. The aim of this study was to evaluate
      the chemical composition of L. philippiana leaf and bark essential oils (EOs)
      using gas chromatography-mass spectrometry (GC-MS), and to quantify its anti
      oomycete activity, specifically against Saprolegnia parasitica and S. australis.
      Only six components were identified in leaf EO, 96.92% of which are
      phenylpropanoids and 3.08% are terpenes. As for bark EO, 29 components were
      identified, representing 67.61% for phenylpropanoids and 32.39% for terpenes.
      Leaf EO was characterized mainly by safrole (96.92%) and beta-phellandrene
      (1.80%). Bark EO was characterized mainly by isosafrole (30.07%), safrole
      (24.41%), eucalyptol (13.89%), methyleugenol (7.12%), and eugenol (6.01%). Bark
      EO has the most promising anti-Saprolegnia activity, with a minimum inhibition
      concentration (MIC) value of 30.0 ug/mL against mycelia growth and a minimum
      fungicidal concentration (MFC) value of 50.0 MUg/mL against spores; for leaf EO,
      the MIC and MFC values are 100 and 125 ug/mL, respectively. These findings
      demonstrate that bark EO has potential to be developed as a remedy for the
      control of Saprolegnia spp. in aquaculture. 

PMID- 25951002
TI  - Composition of the Essential Oil of Salvia ballotiflora (Lamiaceae) and Its
      Insecticidal Activity.
AB  - Essential oils can be used as an alternative to using synthetic insecticides for
      pest management. Therefore, the insectistatic and insecticidal activities of the
      essential oil of aerial parts of Salvia ballotiflora (Lamiaceae) were tested
      against the fall armyworm Spodoptera frugiperda (Lepidoptera: Noctuidae). The
      results demonstrated insecticidal and insectistatical activities against this
      insect pest with concentrations at 80 ug.mL(-1) resulting in 20% larval viability
      and 10% pupal viability. The larval viability fifty (LV50) corresponded to a
      concentration of 128.8 ug.mL(-1). This oil also increased the duration of the
      larval phase by 5.5 days and reduced the pupal weight by 29.2% withrespect to the
      control. The GC-MS analysis of the essential oil of S. ballotiflora showed its
      main components to be caryophyllene oxide (15.97%), and beta-caryophyllene
      (12.74%), which showed insecticidal and insectistatical activities against S.
      frugiperda. The insecticidal activity of beta-caryophyllene began at 80 ug.mL(
      1), giving a larval viability of 25% and viability pupal of 20%. The
      insectistatic activity also started at 80 ug.mL(-1) reducing the pupal weight by
      22.1% with respect to control. Caryophyllene oxide showed insecticidal activity
      at 80 ug.mL(-1) giving a larval viability of 35% and viability pupal of 20%.The
      insectistatic activity started at 400 ug.mL(-1) and increased the larval phase by
      8.8% days with respect to control. The LV50 values for these compounds were 153.1
      and 146.5 ug.mL(-1), respectively.

PMID- 25951003
TI  - Interference of Phenylethanoid Glycosides from Cistanche tubulosa with the MTT
      Assay.
AB  - The MTT assay, as a screening method, has been widely used to measure the
      viability and proliferation of cells. However, it should be noted that MTT assay
      may not accurately reflect the effect of Cistanche tubulosa ethanolic extract on
      EA.hy926 cells viability. To investigate and identity the components responsible
      for the contradictory observations of the MTT assay, echinacoside and acteoside,
      two main phenylethanoid glycosides, from C. tubulosa ethanolic extract were
      isolated. The data derived from CCK-8, Hoechst 33342 and annexin V-FITC/PI assays
      suggest that the caffeyl group present in both isolated compounds was responsible
      for the conflicting results of the MTT assay. These data emphasize the need of
      using a variety of different methods to determine the effect of medicinal agents
      on cell viability to avoid generating misleading results. 

PMID- 25951004
TI  - Antimycobacterial and anti-inflammatory activities of substituted chalcones
      focusing on an anti-tuberculosis dual treatment approach.
AB  - Tuberculosis (TB) remains a serious public health problem aggravated by the
      emergence of M. tuberculosis (Mtb) strains resistant to multiple drugs (MDR).
      Delay in TB treatment, common in the MDR-TB cases, can lead to deleterious life
      threatening inflammation in susceptible hyper-reactive individuals, encouraging
      the discovery of new anti-Mtb drugs and the use of adjunctive therapy based on
      anti-inflammatory interventions. In this study, a series of forty synthetic
      chalcones was evaluated in vitro for their anti-inflammatory and
      antimycobacterial properties and in silico for pharmacokinetic parameters. Seven
      compounds strongly inhibited NO and PGE2 production by LPS-stimulated macrophages
      through the specific inhibition of iNOS and COX-2 expression, respectively, with
      compounds 4 and 5 standing out in this respect. Four of the seven most active
      compounds were able to inhibit production of TNF-alpha and IL-1beta. Chalcones
      that were not toxic to cultured macrophages were tested for antimycobacterial
      activity. Eight compounds were able to inhibit growth of the M. bovis BCG and Mtb
      H37Rv strains in bacterial cultures and in infected macrophages. Four of them,
      including compounds 4 and 5, were active against a hypervirulent clinical Mtb
      isolate as well. In silico analysis of ADMET properties showed that the evaluated
      chalcones displayed satisfactory pharmacokinetic parameters. In conclusion, the
      obtained data demonstrate that at least two of the studied chalcones, compounds 4
      and 5, are promising antimycobacterial and anti-inflammatory agents, especially
      focusing on an anti-tuberculosis dual treatment approach. 

PMID- 25951005
TI  - Effect of chum salmon egg lectin on tight junctions in Caco-2 cell monolayers.
AB  - The effect of a chum salmon egg lectin (CSL3) on tight junction (TJ) of Caco-2
      cell monolayers was investigated. The lectin opened TJ as indicated by the
      decrease of the transepithelial electrical resistance (TER) value and the
      increase of the permeation of lucifer yellow, which is transported via the TJ
      mediated paracellular pathway. The effects of CSL3 were inhibited by the addition
      of 10 mM L-rhamnose or D-galactose which were specific sugars for CSL3. The
      lectin increased the intracellular Ca2+ of Caco-2 cell monolayers, that could be
      inhibited by the addition of L-rhamnose. The fluorescence immunostaining of beta
      actin in Caco-2 cell monolayers revealed that the cytoskeleton was changed by the
      CSL3 treatment, suggesting that CSL3 depolymerized beta-actin to cause reversible
      TJ structural and functional disruption. Although Japanese jack bean lectin and
      wheat germ lectin showed similar effects in the decrease of the TER values and
      the increase of the intracellular Ca2+, they could not be inhibited by the same
      concentrations of simple sugars, such as D-glucose and N-acetyl-D-glucosamine. 

PMID- 25951006
TI  - Qualitative and Quantitative Analysis of Lignan Constituents in Caulis
      Trachelospermi by HPLC-QTOF-MS and HPLC-UV.
AB  - A high-performance liquid chromatography coupled with quadrupole tandem time-of
      flight mass (HPLC-QTOF-MS) and ultraviolet spectrometry (HPLC-UV) was established
      for simultaneous qualitative and quantitative analysis of the major chemical
      constituents in Caulis Trachelospermi, respectively. The analysis was performed
      on an Agilent Zorbax Eclipse Plus C18 column (4.6 mm*150 mm, 5 MUm) using a
      binary gradient system of water and methanol, with ultraviolet absorption at 230
      nm. Based on high-resolution ESI-MS/MS fragmentation behaviors of the reference
      standards, the characteristic cleavage patterns of lignano-9, 9'-lactones and
      lignano-8'-hydroxy-9, 9'-lactones were obtained. The results demonstrated that
      the characteristic fragmentation patterns are valuable for identifying and
      differentiating lignano-9,9'-lactones and lignano-8'-hydroxy-9,9'-lactones. As
      such, a total of 25 compounds in Caulis Trachelospermi were unambiguously or
      tentatively identified via comparisons with reference standards or literature. In
      addition, 14 dibenzylbutyrolatone lignans were simultaneously quantified in
      Caulis Trachelospermi by HPLC-UV method. The method is suitable for the
      qualitative and quantitative analyses of dibenzylbutyrolatone lignans in Caulis
      Trachelospermi.

PMID- 25951007
TI  - Auxin and cytokinin act during gynoecial patterning and the development of ovules
      from the meristematic medial domain.
AB  - The gynoecium is the female reproductive structure of flowering plants, and is
      the site of ovule and seed development. The gynoecium is critical for
      reproductive competence and for agricultural productivity in many crop plants. In
      this review we focus on molecular aspects of the development of the Arabidopsis
      thaliana gynoecium. We briefly introduce gynoecium structure and development and
      then focus on important research advances published within the last year. We
      highlight what has been learned recently with respect to: (1) the role of auxin
      in the differential development of the medial and lateral domains of the
      Arabidopsis gynoecium; (2) the interaction between cytokinin and auxin during
      gynoecial development; (3) the role of auxin in the termination of the floral
      meristem and in the transition of floral meristem to gynoecium; and (4) recent
      studies that suggest a degree of evolutionary conservation of auxin mechanisms
      during gynoecial development in other eudicots.

PMID- 25951008
TI  - Associations Between Reasons to Go Outdoors and Objectively-Measured Walking
      Activity in Various Life-Space Areas Among Older People.
AB  - This cross-sectional study investigated associations between reasons to go
      outdoors and objectively-measured walking activity in various life-space areas
      among older people. During the study, 174 community-dwelling older people aged 75
      90 from central Finland wore an accelerometer over seven days and recorded their
      reasons to go outdoors in an activity diary. The most common reasons for going
      outdoors were shopping, walking for exercise, social visits, and running errands.
      Activities done in multiple life-space areas contributed more to daily step
      counts than those done in the neighborhood or town and beyond. Those who went
      shopping or walked for exercise accumulated higher daily step counts than those
      who did not go outdoors for these reasons. These results show that shopping and
      walking for exercise are common reasons to go outdoors for community-dwelling
      older people and may facilitate walking activity in older age. Future studies on
      how individual trips contribute to the accumulation of steps are warranted. 

PMID- 25951009
TI  - Application of ZnSO4 or Zn-EDTA fertilizer to a calcareous soil: Zn diffusion in
      soil and its uptake by wheat plants.
AB  - BACKGROUND: The objective of this study was to compare the efficiency of two Zn
      sources and two application methods on (i) Zn diffusion from fertilized soil to
      unfertilized soil, (ii) grain Zn concentration and (iii) grain Zn bio
      accessibility to humans. In the laboratory experiment, 20 mg ZnSO4 or 4 mg Zn
      EDTA were applied to a 5 mm and 1 mm-wide space in the soil in the half-cell
      technique. In the greenhouse experiment, Zn-ZnSO4 or Zn
      ethylenediaminetetraacetic acid (Zn-EDTA) was mixed or banded with the soil at a
      rate of 20 or 4 mg Zn kg(-1) , respectively. RESULTS: The results from the
      diffusion experiment showed that both the extractability and the diffusion
      coefficient of Zn were higher when Zn fertilizer was applied to a 1 mm-wide space
      than when it was applied to a 5 mm-wide space. Zn-EDTA had a greater diffusion
      distance than ZnSO4 . The greenhouse experiment showed that the mixed ZnSO4
      application and the Zn-EDTA application (both mixed and banded) treatments
      significantly increased grain Zn concentration and bio-accessibility. The
      positive effect of Zn-EDTA on grain Zn concentrations and bio-accessibility was
      greater than that of ZnSO4 . The banded application reduced the effectiveness of
      ZnSO4 but not of Zn-EDTA. CONCLUSION: It was concluded that Zn-EDTA was a better
      Zn source than ZnSO4 for increasing grain Zn content in a potentially Zn
      deficient calcareous soil.

PMID- 25951010
TI  - Textile/metal-organic-framework composites as self-detoxifying filters for
      chemical-warfare agents.
AB  - The current technology of air-filtration materials for protection against highly
      toxic chemicals, that is, chemical-warfare agents, is mainly based on the broad
      and effective adsorptive properties of hydrophobic activated carbons. However,
      adsorption does not prevent these materials from behaving as secondary emitters
      once they are contaminated. Thus, the development of efficient self-cleaning
      filters is of high interest. Herein, we report how we can take advantage of the
      improved phosphotriesterase catalytic activity of lithium alkoxide doped
      zirconium(IV) metal-organic framework (MOF) materials to develop advanced self
      detoxifying adsorbents of chemical-warfare agents containing hydrolysable P-F, P
      O, and C-Cl bonds. Moreover, we also show that it is possible to integrate these
      materials onto textiles, thereby combining air-permeation properties of the
      textiles with the self-detoxifying properties of the MOF material.

PMID- 25951012
TI  - Concerted Ring Opening and Cycloaddition of Chiral Epoxy Enolsilanes with Dienes.
AB  - Silyl-triflate-catalyzed (4+3) cycloadditions of epoxy enolsilanes with dienes
      provide a mild and chemoselective synthetic route to seven-membered carbocycles.
      Epoxy enolsilanes containing a terminal enolsilane and a single stereocenter
      undergo cycloaddition with almost complete conservation of enantiomeric purity, a
      finding that argues against the involvement of oxyallyl cation intermediates
      which have been previously proposed for these types of reactions. Reported are
      theoretical and experimental investigations of the cycloaddition mechanism. The
      major enantiomers of the cycloadducts are derived from S(N)2-like reactions of
      the silylated epoxide with the diene, in which stereospecific ring opening and
      formation of the two new C-C bonds occur in a single step. Calculations predict,
      and experiments confirm, that the observed small losses of enantiomeric purity
      are traced to a triflate-mediated double S(N)2 cycloaddition pathway.

PMID- 25951015
TI  - Can cervicography replace the ectocervical papanicolaou smear?
AB  - OBJECTIVES: The purpose of this study was to combine the relative strengths of
      two screening tests - the Papanicolaou smear and cervicography - and to determine
      whether their combination is more efficient at evaluating the cervix than is the
      traditional method of cytological assessment alone. METHODS: Two hundred eighty
      five non-pregnant patients qualified for the study. Age range was 17 to 50 years,
      with an average age of 28.2 years. Papanicolaou smears were followed by
      cervicography. RESULTS: Of all patients in whom cervical abnormalities were
      diagnosed via the combination of cervicography and cytology, 90 patients had
      cervical abnormalities. Ten patients would have been missed by this combined
      approach, four of the ten underwent colposcopy, and only one revealed findings
      significant enough for biopsy. CONCLUSIONS: Our results show that a dual
      procedure appears to be superior to either method individually for diagnostic
      capability.

PMID- 25951014
TI  - Study of Carbon Nanotubes as Etching Masks and Related Applications in the
      Surface Modification of GaAs-based Light-Emitting Diodes.
AB  - The surface modification of LEDs based on GaAs is realized by super-aligned
      multiwalled carbon nanotube (SACNT) networks as etching masks. The surface
      morphology of SACNT networks is transferred to the GaAs. It is found that the
      light output power of LEDs based on GaAs with a nanostructured surface morphology
      is greatly enhanced with the electrical power unchanged. 

PMID- 25951016
TI  - Review of outcomes of atypical squamous cells of undetermined significance
      papanicolaou smears for 1991 and 1992, with follow-up through 1995.
AB  - OBJECTIVES: Our aim was to review 1,754 consecutive Papanicolaou (Pap) smears
      from 1991 to 1992 to evaluate initial findings and disease progression through
      December of 1995. METHODS: The study used analysis of data in the Gundersen
      Lutheran Medical Center Colposcopy Clinic's computerized registry. A total of
      1,754 patients were followed, and findings were analyzed for progression and age
      related outcomes. RESULTS: At initial evaluation by a trained ACOG member
      colposcopist, 11% of patients with atypical squamous cells of undetermined
      significance (ASCUS) Pap smears had histologically confirmed cervical
      intraepithelial neoplasia (CIN) I lesion and 7% a CIN II or III lesion. After a
      negative initial evaluation for an ASCUS Pap smear, an additional 8.4% smears
      went on to to demonstrate histologically confirmed CIN II or III, and an
      additional 4.7% revealed a CIN I. CONCLUSIONS: An ASCUS Pap smear requires
      evaluation by a care provider trained in colposcopy and management of abnormal
      Pap smears.

PMID- 25951017
TI  - Knowledge base as a predictor of follow-up compliance after colposcopy.
AB  - OBJECTIVES: Our aim was to determine patient knowledge of cervical dysplasia and
      colposcopy at an inner-city obstetrics and gynecology clinic and the relationship
      of this knowledge base to compliance. METHODS: One hundred six women presenting
      for colposcopy at Thomas Jefferson University Hospital's obstetrics and
      gynecology clinic during an 8-month period were given questionnaires testing
      their knowledge of Papanicolaou smears, colposcopy, cervical dysplasia, and
      cervical cancer. Their medical records were reviewed 12 to 19 months later for
      patient demographics and follow-up compliance. RESULTS: Mean patient score on the
      nine-question test was 3.5 +/- 1.7 (score range, 0-8). Answers to individual
      questions showed that 32.1% of patients understood the purpose of a Papanicolaou
      smear, 52.8% understood the nature of colposcopy, and 24.4% could identify at
      least three risk factors for cervical cancer. Overall compliance with planned
      follow-up was 54.7%. We saw no relationship between test scores and follow-up
      compliance. Correct answers to individual questions did not correlate with
      improved compliance. Age, parity, intercurrent pregnancy, and history of previous
      colposcopy were not predictive of compliance. Follow-up compliance correlated
      with the colposcopic impression of the severity of disease [79.2% for patients
      with high-grade lesions versus 46.9% for all others (p = .005)]. A statistical
      trend was observed in relation to the severity of the initiating cytological
      diagnosis. CONCLUSIONS: Patient knowledge was poor, as demonstrated by our
      questionnaire. Compliance did not correlate with questionnaire scores but rather
      correlated with the colposcopic impression of severity of disease. Increased
      knowledge in patients, therefore, may not necessarily increase compliance.

PMID- 25951018
TI  - Microcolpohysteroscopy: myth or reality?
AB  - OBJECTIVES: Our aim was to compare the diagnostic accuracy of
      microcolpohysteroscopy (MCH) and colposcopy-directed biopsies in the detection of
      precancer and cancer of the uterine cervix. PATIENTS AND METHODS: Between January
      and December 1994, a total of 174 patients underwent colposcopic and MCH
      examinations. Direct biopsies were obtained under colposcopic and MCH guidance.
      Diagnostic accuracies of the two methods were compared using the chisquare test
      and the kappa coefficient. RESULTS: Colposcopy showed an overall diagnostic
      accuracy of 39.7% (69 of 174) with a sensitivity of 50.5%, specificity of 23.2%,
      positive predictive value of 50%, and negative predictive value of 23.5%. The
      percentage of agreement between MCH diagnosis and histological findings was 92.4%
      for cervical intraepithelial neoplasia lesions, 92.5% for human papillomavirus,
      and 100% for invasive cancer. Of the total 174 cases, colposcopy examination was
      considered satisfactory in 134 (77%) and unsatisfactory in 40 (23%). In the 40
      cases when the limits of the squamocolumnar epithelium could not be seen at
      colposcopy, satisfactory MCH examinations were obtained in cervical lesions
      measuring no more than 10 mm in endocervical depth (29 cases), and unsatisfactory
      MCH examinations were obtained in cervical lesions measuring at least 10 mm of
      endocervical depth (11 cases). The overall MCH failure rate was 6.3% (11 of 174).
      CONCLUSIONS: MCH appears more reliable than colposcopy and is capable of showing
      lesions undetectable by colposcopy.

PMID- 25951013
TI  - Catenanes: fifty years of molecular links.
AB  - Half a century after Schill and Luttringhaus carried out the first directed
      synthesis of a [2]catenane, a plethora of strategies now exist for the
      construction of molecular Hopf links (singly interlocked rings), the simplest
      type of catenane. The precision and effectiveness with which suitable templates
      and/or noncovalent interactions can arrange building blocks has also enabled the
      synthesis of intricate and often beautiful higher order interlocked systems,
      including Solomon links, Borromean rings, and a Star of David catenane. This
      Review outlines the diverse strategies that exist for synthesizing catenanes in
      the 21st century and examines their emerging applications and the challenges that
      still exist for the synthesis of more complex topologies. 

PMID- 25951019
TI  - Cervical cancer screening with papanicolaou smear plus speculoscopy by nurse
      practitioners in a health maintenance organization.
AB  - OBJECTIVES: We set out to evaluate the utility of a magnified chemiluminescent
      screening examination (speculoscopy) as an adjunct to the Papanicolaou (Pap)
      smear in detection of cervical pathological processes by nurse practitioners and
      midwives in a health maintenance organization setting. PATIENTS AND METHODS:
      Patients who presented for routine screening (N = 689) received a Pap smear and
      speculoscopy examination. If the Pap smear or speculoscopy result was positive,
      colposcopy was performed and biopsies were obtained from women with positive
      colposcopies. Data were analyzed using McNemar's adaptation of the chi-square
      test for correlated proportions. RESULTS: In 80 patients from whom biopsies were
      obtained, Pap smear alone detected 67% of (6 of 9) and speculoscopy alone
      detected 77% of (7 of 9) high-grade squamous intraepithelial lesions (HGSILs).
      Pap smear alone detected 26% of low-grade squamous intraepithelial lesions
      (LGSILs) (10 of 38) whereas speculoscopy alone detected 84% (32 of 38) (p <
      .001). Combined use of Pap smear and speculoscopy showed a trend (p = .073)
      toward enhanced detection of HGSIL compared with either the Pap smear alone or
      speculoscopy alone. CONCLUSIONS: Speculoscopy can be included in a nurse
      practitioner- and midwife-based cervical screening program, and the addition of
      this modality enhances the sensitivity of cervical screening by finding more high
      grade and low-grade cervical disease than does pap smear alone.

PMID- 25951020
TI  - Clinical significance of cervical smears with atypical squamous cells of
      undetermined significance designated "favor reactive" or "favor preneoplastic".
AB  - OBJECTIVE: Our aim was to determine the clinical significance of the two
      subgroups of atypical squamous cells of undetermined significance (ASCUS),
      designated "favor reactive" and "favor preneoplastic." MATERIALS AND METHODS:
      Cervical Papanicolaou smears with a diagnosis of ASCUS favor reactive or ASCUS
      favor preneoplastic were retrieved between October 1993 and September 1994 (12
      months). Cases with follow-up colposcopic biopsies within 6 months were reviewed.
      RESULTS: Eighteen percent of 67 ASCUS favor reactive patients and 39% of 264
      ASCUS favor preneoplastic patients had follow-up biopsies, respectively. Squamous
      intra-epithelial lesions were diagnosed on biopsies in 58% of cases of ASCUS
      favor reactive patients and in 61 % of cases of ASCUS favor preneoplastic
      patients. CONCLUSIONS: According to the results, a high percentage of patients in
      both subgroups of ASCUS patients were diagnosed with squamous intraepithelial
      lesions on follow-up biopsies. Major prognostic difference is not apparent
      between the two subgroups.

PMID- 25951021
TI  - Internet survey of colposcopy practices.
AB  - OBJECTIVES: Our aim was to use electronic mail to survey health care providers
      about practice patterns involving atypical Papanicolaou smears. MATERIALS AND
      METHODS: A six-item questionnaire evaluating demographics and practice patterns
      was distributed on two Internet electronic mail forums: OB-GYN-L and GYN-DOCS.
      There were approximately 340 eligible participants. RESULTS: A total of 88 (26%)
      completed surveys were received. The percentage of respondents to the survey who
      would refer patients for colposcopy was 42% for findings of atypical squamous
      cells of undetermined significance, unqualified (ASCUS-unqualified), 92% for
      findings of ASCUS-favoring neoplastic change, 18% for ASCUS-favoring reactive
      change, and 95% for low-grade squamous intraepithelial lesions (LGSILs). With the
      exception of ASCUS-favoring neoplastic change as compared to LGSILs, each
      category was found to be statistically different from the others (p < .001) in
      colposcopy practice. CONCLUSIONS: This survey of practice patterns suggests that
      subdividing ASCUS into types favoring either reactive or neoplastic changes has
      been adopted clinically. LGSIL and ASCUS-favoring neoplastic change are triaged
      to colposcopy, whereas findings of ASCUS-favoring reactive changes are followed
      by colposcopy. Surveys conducted via electronic mail may have lower response
      rates than postal surveys.

PMID- 25951022
TI  - The role of speculoscopy in the diagnosis of cervical dysplasia.
AB  - BACKGROUND: Concern about false negative screening cytology has led to the
      development of adjunctive tests, among them speculoscopy. Speculoscopy involves
      cervical examination after acetic acid wash with 5X magnifying loupes under
      chemiluminescent illumination. CONCLUSIONS: Limited data support a role for
      speculoscopy to improve screening yield and allow triage of patients with
      borderline cytology, but indications and strategies for use require further
      definition.

PMID- 25951023
TI  - ASCCP Practice Guidelines: The Follow-Up System for Abnormal Cervical Cytological
      Findings.

PMID- 25951025
TI  - Home study course: summer 1997.

PMID- 25951024
TI  - So what do you think now?

PMID- 25951026
TI  - The american society for colposcopy and cervical pathology.

PMID- 25951027
TI  - A postmenopausal patient with atypical glandular cells after supracervical
      hysterectomy.

PMID- 25951028
TI  - What do you recommend to patients who request automated pap smear screening?

PMID- 25951029
TI  - Response to clinical question posed in volume 1, number 2: atypical glandular
      cells of undetermined significance.

PMID- 25951030
TI  - Pregnancy-related fibroadenoma of ectopic breast tissue in the vulva.
AB  - BACKGROUND: Pregnancy-related vulvar fibroadenoma of ectopic breast tissue is
      rare. Management involves diagnosing the mass as a fibroadenoma by physical
      examination and delaying excision until the postpartum period. CASE: A 31-year
      old multigravid woman at 29 weeks' gestation had a right labial mass that was
      increasing in size. Physical examination showed accessory breast tissue in the
      left axilla and three vulvar masses, the largest vulvar mass measuring 4 * 5 cm.
      Suspicion of malignancy was low, so the patient was serially examined during the
      pregnancy and the vulvar masses were excised during the postpartum period. The
      final diagnosis was fibroadenoma of ectopic breast tissue. CONCLUSION:
      Fibroadenoma of ectopic breast tissue can occur during pregnancy. Diagnosis and
      serial physical examinations are the appropriate course of management during
      pregnancy. A fine-needle aspiration biopsy can be performed during pregnancy to
      confirm the diagnosis. The tumors seldom regress spontaneously and so should be
      removed during the postpartum period.

PMID- 25951031
TI  - Vulvar pain: diagnoses, evaluation, and management.
AB  - In 1975, the International Society for the Study of Vulvar Disease recommended
      the term vulvodynia to describe vulvar pain regardless of its cause. For most
      clinicians, vulvar pain is, to say the least, confusing. It is not one disease
      but, in most cases, the manifestation of several diseases often erroneously
      lumped together because they are uncomfortable and occur on the vulva. Sometimes
      these diseases have physical findings that are clearly diagnostic, and sometimes
      there are neither physical findings nor apparent etiology. 

PMID- 25951032
TI  - A design equation for low dosage additives that accelerate nucleation.
AB  - Additives are used to control nucleation in many natural and industrial
      environments. However, the mechanisms by which additives inhibit or accelerate
      solute precipitate nucleation are not well understood. We propose an equation
      that predicts changes in nucleation barriers based on the adsorption properties
      and concentrations of trace additives. The equation shows that nucleant efficacy
      depends on the product of an adsorption equilibrium constant and the reduction in
      interfacial tension. Moreover, the two factors that determine the potency of
      additives are related to each other, suggesting that assays of just one property
      might facilitate additive design. We test the design equation for a Potts lattice
      gas model with surfactant-like additives in addition to solutes and solvents. 

PMID- 25951033
TI  - In Reply: Volumetric Arc Therapy (RapidArc) vs Gamma Knife Radiosurgery for
      Multiple Brain Metastases: Not Only a Dosimetric Issue.

PMID- 25951034
TI  - Hyperspectral diagnostic imaging of the cervix: report on a new investigational
      device.
AB  - OBJECTIVE: To describe our experience with a noncontact in vivo fluorescence
      imaging device for the detection and localization of cervical intraepithelial
      neoplasia (CIN). MATERIALS AND METHODS: Sixty-two women with abnormal
      Papanicolaou (Pap) smears, and 4 women with normal Pap smears, were recruited to
      undergo fluorescence imaging of the cervix during colposcopy. After topically
      applying dilute acetic acid, the surface of the cervix was scanned with 365 nm
      ultraviolet light for about 12 sec. Colposcopy and biopsies of visualized lesions
      were then performed. The fluorescence emission curves generated by normal
      cervical tissue and various states of cervical pathology were inspected and
      assigned relative scores of 1-5 based on the height and slope of the curves at
      peak fluorescence emissions. A score of 1 indicated a curve with high magnitude
      and distinct peak, and a score of 5 described a curve of low magnitude and
      rounded/flattened peak. Scores of 2-4 represented curves with incremental changes
      of about 25% in the height of the curve between scores of 1 and 5. Biopsies were
      classified as high grade (HG, CIN 2/3), low grade (LG, HPV/CIN 1), or
      nondysplastic (ND). Among women with abnormal Pap smears, only those who had
      biopsies with concordant interpretations by two independent pathologists were
      included in the descriptive analysis. All of the patients with normal Pap smears
      were included. RESULTS: A total of 35 women were included in the analysis. Of 62
      women with abnormal Pap smears who underwent fluorescence imaging and colposcopy,
      31 met the inclusion criteria. Among these 31 women, Pap smears consisted of 6
      atypical squamous cells of undetermined significance (ASCUS), 16 low-grade
      squamous intraepithelial lesions (LGSILs), and 9 high-grade squamous
      intraepithelial lesions (HGSILs). Of the 4 women with normal Pap smears, 1 had an
      abnormal colposcopy and a nondysplastic biopsy. Among all 35 women, 42 total
      biopsies were included, consisting of 11 HG, 25 LG, and 6 ND. Normal squamous
      tissue generated a score of 1, normal metaplastic tissue a score of 2 or 3, and
      normal columnar tissue of score of 5 in 35/35 (100%) women. Among the 11 HG
      lesions, 8 had a score of 4 and 2 had a score of 5. One case was uninterpretable
      due to a low signal-to-noise ratio. Among the 25 LG lesions, 15 had a score of 3,
      6 had a score of 4 or 5, 2 had a score of 1, and 2 cases were uninterpretable.
      CONCLUSIONS: HG lesions generated spectra distinct from normal tissue in 8/10
      (80%) evaluable cases, but LG lesions generated spectra indistinguishable from
      that of normal metaplastic tissue. Further modifications to this technique are
      needed before an objective, reproducible, and discriminatory scoring system can
      be developed. ?.

PMID- 25951035
TI  - Endocervical curettage in cervical evaluation.
AB  - OBJECTIVE: To evaluate the role of endocervical curettage (ECC) in the diagnosis
      of cervical intraepithelial neoplasia. MATERIALS AND METHODS: Retrospectively we
      studied 581 patients who had ECC, 43 (7.4%) had cervical intraepithelial lesions
      (CIN) 1 ECC, 23 (4.0%) CIN 2-3 ECC, and 515 negative ECC (88.6%). Analysis of
      variance was used to compare for age and parity, and Pearson's chi-square test
      was used to analyze the association with other variables such as cytology,
      images, acetowhite epithelium, microbiopsy, and ECC. Significance level was set
      at p = 0.05. RESULTS: Age for CIN 1 ECC was at 32.3 (16-66) years; parity was at
      0.82 (parity 0-7) compared with 35.2 (18-70) years and parity at 1.52 (parity 0
      12) for CIN 2-3 ECC, and 36.1 (14-68) years, parity at 1.1 (parity 0-10) for
      negative ECC. ECC is associated with Cytobrush cytology (Zelsmyr Cytobrush,
      International Cytobrush Inc., Hollywood. FL) (p = 0.000) in CIN 2-3 ECC and high
      grade squamous intraepithelial lesion (HGSIL) cytology. Positive ECC was not
      overrepresented in unsatisfactory colposcopy (14/61, 23%) compared with negative
      ECC (158/526, 30%, p = 0.43). If positive ECC is not associated with the presence
      of significant acetowhite epithelium, a net association (p = 0.000) was observed
      between CIN 1 microbiopsies and CIN 1 ECC 9 (12/19), and CIN 2-3 biopsies and CIN
      2-3 ECC (12/17). Conization for CIN 2-3 ECC (n = 23) yielded 15 CIN 2-3, two CIN
      1, one microinvasive cervical cancer, one cancer of the cervix, and four negative
      cones. CONCLUSIONS: Positive endocervical curettage is associated with
      endocervical cytology and microbiopsy. In ablative treatments, when low-grade
      squamous intraepithelial lesion (LGSIL) smear, satisfactory colposcopy, and CIN 1
      biopsy is observed, ECC appears unnecessary since CIN 2-3 ECC was not observed in
      these patients. All other cases should have ECC prior to ablative therapy. CIN 2
      3 ECC, commands conization, in order to eliminate invasive cancer, and confirm
      and treat CIN 2-3. ?.

PMID- 25951037
TI  - President's Address: International Federation for Cervical Pathology and
      Colposcopy.

PMID- 25951036
TI  - Treatment of external genital warts.
AB  - ? ABSTRACT: : To date the most widely used therapies for the treatment of
      external genital warts (EGWs) have been ablative techniques, some of which have
      serious side effects and result in high recurrence. This is frustrating for both
      patients and physicians. More recently, patient-applied therapies have become
      available, which offer several advantages over provider-administered therapies,
      and are generally preferred by the patients. The newest of these is imiquimod 5%
      cream. Its mode of action, stimulating the immune system to deal with the human
      papillomavirus (HPV), provides an effective treatment. Results obtained in
      clinical trials with imiquimod are described here, in the context of a
      recommended treatment protocol for EGWs. In addition, the potential for imiquimod
      to treat other HPV lesions is discussed. ?.

PMID- 25951038
TI  - Lower genital tract metastases of placental site trophoblastic tumor: case report
      and review of the literature.
AB  - OBJECTIVES: We present a case of metastatic placental site trophoblastic tumor
      (PSTT) and review the English literature on this entity. MATERIALS AND METHODS:
      In addition to the case presentation, literature review describes 23 additional
      cases with differing treatments and length of survival. RESULTS: The patient is
      free of disease more than 5 years after diagnosis. She received multimodality
      treatment including surgery, chemotherapy, and radiotherapy. Eleven other
      patients survived the disease from 12 to 36 months after initial diagnosis.
      CONCLUSION: Metastatic PSTT has a poor prognosis and requires aggressive
      treatment. ?.

PMID- 25951039
TI  - A case of prostatic rhabdomyosarcoma in childhood.
AB  - ? ABSTRACT: : Rhabdomyosarcoma of the prostate is rare, especially in childhood.
      The treatment of this neoplasm has been destructive surgery with adjuvant
      chemotherapy or radiotherapy. These treatment recommendations have been revised
      to suggest conservative surgery plus adjuvant chemotherapy and radiotherapy. We
      report treatment of prostatic rhabdomyosarcoma in a child with a long-term follow
      up. ?.

PMID- 25951040
TI  - Home study course: summer 2000.
AB  - ? OBJECTIVE: : The Home Study Course is intended for the practicing colposcopist
      or practitioner who is seeking to develop or enhance his or her colposcopic
      skills. The goal of the course is to present colposcopic cases that are unusual
      or instructive in terms of appearance, presentation, or management, or that
      demonstrate new and important knowledge in the area of colposcopy or pathology.
      Participants may benefit from reading and studying the material or from testing
      their knowledge by answering the questions. ? ACCME ACCREDITATION: : The American
      Society for Colposcopy and Cervial Pathology (ASCCP) is accredited by the
      Accreditation Council for Continuing Medical Education (ACCME) to sponsor
      continuing medical education for physicians. The ASCCP designates this continuing
      medical education activity for 1 credit hour in Category I of the Physician's
      Recognition Award of the American Medical Association. Credit is available for
      those who choose to apply. The Home Study Course is planned and produced in
      accordance with the ACCME's Essential Areas and Elements.

PMID- 25951041
TI  - The american society for colposcopy and cervical pathology: hagerstown, MD.

PMID- 25951042
TI  - Role of rice cytosolic hexokinase OsHXK7 in sugar signaling and metabolism.
AB  - We characterized the function of the rice cytosolic hexokinase OsHXK7 (Oryza
      sativa Hexokinase7), which is highly upregulated when seeds germinate under O2 
      deficient conditions. According to transient expression assays that used the
      promoter:luciferase fusion construct, OsHXK7 enhanced the glucose (Glc)-dependent
      repression of a rice alpha-amylase gene (RAmy3D) in the mesophyll protoplasts of
      maize, but its catalytically inactive mutant alleles did not. Consistently, the
      expression of OsHXK7, but not its catalytically inactive alleles, complemented
      the Arabidopsis glucose insensitive2-1 (gin2-1) mutant, thereby resulting in the
      wild type characteristics of Glc-dependent repression, seedling development, and
      plant growth. Interestingly, OsHXK7-mediated Glc-dependent repression was
      abolished in the O2 -deficient mesophyll protoplasts of maize. This result
      provides compelling evidence that OsHXK7 functions in sugar signaling via a
      glycolysis-dependent manner under normal conditions, but its signaling role is
      suppressed when O2 is deficient. The germination of two null OsHXK7 mutants,
      oshxk7-1 and oshxk7-2, was affected by O2 deficiency, but overexpression enhanced
      germination in rice. This result suggests the distinct role that OsHXK7 plays in
      sugar metabolism and efficient germination by enforcing glycolysis-mediated
      fermentation in O2 -deficient rice. 

PMID- 25951044
TI  - Autoimmune diseases: What have we learned from mice?

PMID- 25951045
TI  - Low dialysate potassium and central arterial pressure waveform.
AB  - BACKGROUND: Cardiovascular mortality is high in hemodialysis (HD) patients. Early
      arterial pressure wave reflections predict mortality in HD patients, and HD
      acutely improves the central pressure waveform. Potassium (K) plays a crucial
      role in cardiac electrophysiology, and patients with end-stage kidney disease
      depend on HD for neutral K balance. We aimed to study the impact of dialysate K
      concentrations on central arterial pressure waveform. METHODS: Thirty-three
      chronic HD patients were studied before and after a HD session, and the
      prescribed dialysate K concentration was recorded. In a subset of 23 patients
      without arrhythmias, pulse wave analysis was performed on radial arteries. Nine
      patients had dialysate K set to 1 mmol/L (group 1), and 14 patients had K set to
      2 or 3 mmol/L (group 2). Augmentation index (AIx), defined as difference between
      the second and first systolic peak divided by central pulse pressure, was used as
      a measure of arterial stiffness. RESULTS: HD reduced the AIx in group 1 only (p =
      0.0005). Likewise, central systolic pressure was reduced in group 1 only (p =
      0.006). The relative reduction of AIx post-HD was significantly higher in group 1
      compared with group 2 (p < 0.0001). The association between low dialysate K and
      AIx reduction remained statistically significant after adjustment for variables
      including the change in central and peripheral systolic pressure and mean
      arterial pressure. CONCLUSION: Low dialysate K is strongly and independently
      associated with the acute improvement of AIx.

PMID- 25951046
TI  - Wideband Absorbance Outcomes in Newborns: A Comparison With High-Frequency
      Tympanometry, Automated Brainstem Response, and Transient Evoked and Distortion
      Product Otoacoustic Emissions.
AB  - OBJECTIVES: The purpose of this study was to evaluate the test performance of
      wideband absorbance (WBA) in terms of its ability to predict the outer and middle
      ear status as determined by nine reference standards. DESIGN: Automated auditory
      brainstem response (AABR), high-frequency (1000 Hz) tympanometry (HFT), transient
      evoked otoacoustic emission (TEOAE), and distortion product otoacoustic emission
      (DPOAE) tests were performed on 298 ears (144 right, 154 left) of 192 (108 males,
      84 females) neonates with a mean age of 43.7 hours (SD = 21.3, range = 8.3 to
      152.2 hr). WBA was measured from 0.25 to 8 kHz using clicks under ambient
      pressure conditions. Test performance of WBA was assessed in terms of its ability
      to identify conductive conditions in neonates when compared with nine reference
      standards (including four single tests and five test batteries) using the
      receiver operating characteristic analysis. RESULTS: The test performance of WBA
      against the test battery reference standards was better than that against single
      test reference standards. The area under the receiver operating characteristic
      curve reached a high value of 0.78 for HFT + TEOAE + DPOAE and AABR + TEOAE +
      DPOAE reference standards. Within the ears that passed each of the reference
      standards, there were no significant differences in WBA. However, for the ears
      that failed each of the test standards, there were significant differences in
      WBA. The region between 1 and 4 kHz provided the best discriminability to
      evaluate the conductive status compared with other frequencies. CONCLUSIONS: WBA
      is a desirable measure of conductive conditions in newborns due to its high
      performance in classifying ears with conductive loss as determined by the best
      performing surrogate gold standards (HFT + TEOAE + DPOAE and AABR + TEOAE +
      DPOAE).

PMID- 25951043
TI  - The role of STAT3 in autophagy.
AB  - Autophagy is an evolutionarily conserved process in eukaryotes that eliminates
      harmful components and maintains cellular homeostasis in response to a series of
      extracellular insults. However, these insults may trigger the downstream
      signaling of another prominent stress responsive pathway, the STAT3 signaling
      pathway, which has been implicated in multiple aspects of the autophagic process.
      Recent reports further indicate that different subcellular localization patterns
      of STAT3 affect autophagy in various ways. For example, nuclear STAT3 fine-tunes
      autophagy via the transcriptional regulation of several autophagy-related genes
      such as BCL2 family members, BECN1, PIK3C3, CTSB, CTSL, PIK3R1, HIF1A, BNIP3, and
      microRNAs with targets of autophagy modulators. Cytoplasmic STAT3 constitutively
      inhibits autophagy by sequestering EIF2AK2 as well as by interacting with other
      autophagy-related signaling molecules such as FOXO1 and FOXO3. Additionally, the
      mitochondrial translocation of STAT3 suppresses autophagy induced by oxidative
      stress and may effectively preserve mitochondria from being degraded by
      mitophagy. Understanding the role of STAT3 signaling in the regulation of
      autophagy may provide insight into the classic autophagy model and also into
      cancer therapy, especially for the emerging targeted therapy, because a series of
      targeted agents execute antitumor activities via blocking STAT3 signaling, which
      inevitably affects the autophagy pathway. Here, we review several of the
      representative studies and the current understanding in this particular field. 

PMID- 25951047
TI  - The Impact of Auditory Processing and Cognitive Abilities in Children.
AB  - OBJECTIVES: To examine the links between auditory processing (AP) test results,
      functional deficits, and cognitive abilities. DESIGN: One hundred and fifty-five
      children, ages 7-12 years, comprising 50 control children and 105 children
      referred for AP assessment, all with normal peripheral hearing, completed an AP
      and cognitive (sustained attention, auditory working memory, and nonverbal
      intelligence) test battery. Functional outcome measures of listening ability
      (developed using questionnaires from parent, teacher, and child respondents) and
      reading fluency were also collected. RESULTS: AP scores for dichotic digits,
      frequency pattern, and listening in spatialized noise-sentences test baseline
      scores showed significant intertask correlations, and significant correlations
      with functional outcomes. The gaps in noise task showed correlation with reading
      fluency only. The AP tasks of masking level differences and spatial advantage
      showed no correlation with listening ability or reading fluency. Results showed
      significantly poorer cognitive abilities overall in the children referred for AP
      assessment compared with the control group. Within the referred group, children
      diagnosed with an auditory processing disorder had significantly poorer cognitive
      abilities than those passing the test battery. Correlation and regression studies
      showed significant associations between AP and cognitive scores. The results of
      multilinear regression analyses showed that the associations of AP scores with
      listening and academic results were no longer significant when cognitive scores
      were also included as predictors. CONCLUSIONS: A complex interaction of cognitive
      abilities and AP scores is evident. For many children with listening
      difficulties, who perform poorly on AP tasks, cognitive deficits are also in
      place. Although the direction of causality is unclear, it is likely that these
      cognitive deficits are causing the perceived difficulty and/or are having a
      significant effect on the test results. Interpretation of AP tests requires
      consideration of how cognitive abilities may have impacted on not only task
      results but also the functional difficulties experienced by the child.

PMID- 25951048
TI  - Effects of Nonlinear Frequency Compression on ACC Amplitude and Listener
      Performance.
AB  - OBJECTIVES: Nonlinear frequency compression is a signal processing technique used
      to increase the audibility of high-frequency speech sounds for hearing aid users
      with sloping, high-frequency hearing loss. However, excessive compression ratios
      may reduce spectral contrast between sounds and negatively impact speech
      perception. This is of particular concern in infants and young children who may
      not be able to provide feedback about frequency compression settings. This study
      explores the use of an objective cortical auditory evoked potential that is
      sensitive to changes in spectral contrast, the acoustic change complex (ACC), in
      the verification of frequency compression parameters. DESIGN: ACC responses were
      recorded from adult listeners to a spectral ripple contrast stimulus that was
      processed using a range of frequency compression ratios (1:1, 1.5:1, 2:1, 3:1,
      and 4:1). Vowel identification, consonant identification, speech recognition in
      noise (QuickSIN), and behavioral ripple discrimination thresholds were also
      measured under identical frequency compression conditions. In Experiment 1, these
      tasks were completed in 10 adults with normal hearing. In Experiment 2, these
      same tasks were repeated in 10 adults with sloping, high-frequency hearing loss.
      RESULTS: Repeated measures analysis of variance was completed for each task and
      each group with frequency compression ratio as the within-subjects factor.
      Increasing the compression ratio did not affect vowel identification for the
      normal hearing group but did cause a significant decrease in vowel identification
      for the hearing-impaired listeners. Increases in compression ratio were
      associated with significant decrements in ACC amplitudes, consonant
      identification scores, ripple discrimination thresholds, and speech perception in
      noise scores for both groups of listeners. CONCLUSIONS: The ACC response, like
      speech and nonspeech perceptual measures, is sensitive to frequency compression
      ratio. Additional study is needed to establish optimal stimulus and recording
      parameters for the clinical application of this measure in the verification of
      hearing aid frequency compression settings.

PMID- 25951049
TI  - On granular elasticity.
AB  - Mesoscopic structures form in dense granular materials due to the self
      organisation of the constituent particles. These structures have internal
      structural degrees of freedom in addition to the translational degree of freedom.
      The resultant granular elasticity, which exhibits intrinsic variations and
      inevitable relaxation, is a key quantity that accounts for macroscopic solid- or
      fluid-like properties and the transitions between them. In this work, we propose
      a potential energy landscape (PEL) with local stable basins and low elastic
      energy barriers to analyse the nature of granular elasticity. A function for the
      elastic energy density is proposed for stable states and is further calibrated
      with ultrasonic measurements. Fluctuations in the elastic energy due to the
      evolution of internal structures are proposed to describe a so-called
      configuration temperature T(c) as a counterpart of the classical kinetic granular
      temperature T(k) that is attributed to the translational degrees of freedom. The
      two granular temperatures are chosen as the state variables, and a fundamental
      equation is established to develop non-equilibrium thermodynamics for granular
      materials. Due to the relatively low elastic energy barrier in the PEL, granular
      elasticity relaxes more under common mechanical loadings, and a simple model
      based on mean-field theory is developed to account for this behaviour. 

PMID- 25951050
TI  - Grading of atypia in genital skin lesions: routine microscopic evaluation and use
      of p16 immunostaining.
AB  - BACKGROUND: p16 immunostaining has been used to aid and improve the
      histopathologic evaluation of equivocal cervical lesions with associated low
      grade or high-grade dysplasia. However, the utility of p16 immunostaining in the
      diagnosis of atypical genital skin lesions remains debatable. METHODS: We
      conducted a cross-sectional study of genital skin lesions with varying degrees of
      atypia. Four pathologists assessed lesional atypia and interpreted hematoxylin
      and eosin (H&E) staining and p16 immunostaining without knowledge of original
      diagnosis. Our primary outcomes were diagnostic agreement and test performance of
      p16 immunostaining compared to consensus H&E diagnosis. RESULTS: Our sample was
      comprised of 23 cases of atypical genital skin lesions. p16 immunostaining was
      negative in all cases of reactive atypia (n = 3) and the majority (n = 7 of 8;
      88%) of low-grade squamous intraepithelial lesions (LSILs). The majority (n = 10
      of 12; 83%) of high-grade squamous intraepithelial lesions (HSIL) were p16
      positive. Diagnostic agreement for histopathologic assessment using H&E staining
      was moderate (kappa = 0.44), while inter-observer agreement of p16 immunostaining
      was excellent (kappa = 0.87). Compared to consensus diagnosis using H&E staining,
      p16 immunostaining performed well (sensitivity 83.3%; specificity 90.9%).
      CONCLUSIONS: p16 immunostaining may be a useful adjunctive marker for assessing
      dysplasia in genital skin lesions and increasing diagnostic agreement among
      pathologists.

PMID- 25951051
TI  - Niche divergence accelerates evolution in Asian endemic Procapra gazelles.
AB  - Ecological niche divergence and adaptation to new environments are thought to
      play important roles in driving speciation. Whether recently evolved species show
      evidence for niche divergence or conservation is vital towards understanding the
      role of ecology in the process of speciation. The genus Procapra is an ancient,
      monophyletic lineage endemic to Asia that contains three extant species (P.
      gutturosa, P. przewalskii and P. picticaudata). These species mainly inhabit the
      Qinghai-Tibetan and Mongolian Plateaus, and today have primarily allopatric
      distributions. We applied a series of geographic information system-based
      analyses to test for environmental variation and niche divergence among these
      three species. We found substantial evidence for niche divergence in species'
      bioclimatic preferences, which supports the hypothesis that niche divergence
      accelerates diversification in Procapra. Our results provide important insight
      into the evolutionary history of ungulates in Asia and help to elucidate how
      environmental changes accelerate lineage diversification. 

PMID- 25951052
TI  - Effects of Waterborne Lead Exposure in Mozambique Tilapia: Oxidative Stress,
      Osmoregulatory Responses, and Tissue Accumulation.
AB  - We studied the oxidative stress and osmoregulatory damage as well as the
      accumulation of lead in Mozambique Tilapia Oreochromis mossambicus exposed to
      different sublethal concentrations-low, medium, and high (0.5, 2.5, and 5.0 mg/L)
      of waterborne lead for 14 d in a semistatic condition. The accumulated levels of
      Na+, K+-ATPase, glutathione (GSH), and thiobarbituric acid reactive substances
      (TBARS) were determined from samples of gill, liver, intestine, brain, kidney,
      and muscle tissues. At the end of the experiment, the GSH levels of most tissues
      were higher in the treated group than in the control group (especially in the
      liver and kidney) but lower in the intestine. The levels of TBARS in the gill and
      brain tissues of the fish exposed to high lead doses were significantly higher
      than those of fish in the control group. Na+, K+-ATPase activity seemed to be
      significantly inhibited in the gill, intestine, and brain tissues across all
      treatment groups. At the end of the study, the total amount of lead that had
      accumulated within the various tissues ranked as follows: intestines > kidney >
      brain > gill > liver > muscle. Our findings suggest that sublethal concentrations
      of lead can disrupt the health of Mozambique Tilapia and cause oxidative stress
      and osmoregulatory damage.

PMID- 25951053
TI  - Treg responses are associated with PM2.5-induced exacerbation of viral
      myocarditis.
AB  - The adverse cardiovascular events induced by ambient fine particles (PM2.5) are
      paid more attention in the world. The current study was conducted to explore the
      mechanisms of T regulatory cells (Treg) responses in PM2.5-induced exacerbation
      of viral myocarditis. The male BALB/c mice were administered an intratracheal
      (i.t.) instillation of 10 mg/kg b.w. PM2.5 suspension. Twenty-four hours later,
      the mice were injected intraperitoneally (i.p.) with 100 MUl of coxsackievirus B3
      (CVB3) diluted in Eagle's minimal essential medium (EMEM). Seven days after the
      treatment, serum, splenetic, and cardiac tissues were examined. The results
      showed that pre-exposure to PM2.5 aggravated the cardiac inflammation in the CVB3
      infected mice along with an increase of Treg cells in the spleen. The mRNA
      expressions of interleukin-6 (IL-6), TNF-alpha, transforming growth factor-beta
      (TGF-beta), and Foxp3 were up-regulated in the PM2.5-pretreated mice than that in
      the CVB3-treated mice. Similar results were found in the sera. In addition,
      compared with the CVB3-treated mice, the cardiac protein expression of TGF-beta
      increased in the PM2.5-pretreated mice. These results demonstrated that
      preexposure to PM2.5 exacerbated virus-induced myocarditis possibly through the
      depression of the immune response and increase of inflammation in myocardium
      through the Treg responses.

PMID- 25951055
TI  - Early Observation of Extracellular Matrix-Derived Hydrogels for Corneal Stroma
      Regeneration.
AB  - A lack of healthy transplantable tissue to treat corneal blindness has led
      researchers to investigate the development and application of different scaffold
      materials for corneal tissue engineering and regeneration. In this study,
      hydrogels fabricated from decellularized corneal extracellular matrix were
      developed as a new approach to corneal stromal tissue regeneration. Porcine
      corneas were decellularized using a technique that combined freeze-thaw cycles
      with a nuclease treatment. The corneas were then freeze-dried, milled, and
      digested in an acidic pepsin solution that was used to form a hydrogel after
      adjusting the pH and gelation temperature. The resultant corneal matrix hydrogels
      (CMHs) were seeded with human corneal stromal cells and cultured for several
      days. When compared to collagens hydrogels, CMHs had superior optical
      transparency, similar mechanical properties, and were better able to retain the
      stromal cells native keratocyte phenotype. The CMHs also supported cell viability
      and proliferation and contained sulfated glycosaminoglycan, a vital constituent,
      for maintaining corneal transparency. These results suggest that the CMHs could
      provide an exceptional biomaterial for corneal stroma regeneration. 

PMID- 25951054
TI  - Identification and Characterization of microRNAs during Maize Grain Filling.
AB  - The grain filling rate is closely associated with final grain yield of maize
      during the period of maize grain filling. To identify the key microRNAs (miRNAs)
      and miRNA-dependent gene regulation networks of grain filling in maize, a deep
      sequencing technique was used to research the dynamic expression patterns of
      miRNAs at four distinct developmental grain filling stages in Zhengdan 958, which
      is an elite hybrid and cultivated widely in China. The sequencing result showed
      that the expression amount of almost all miRNAs was changing with the development
      of the grain filling and formed in seven groups. After normalization, 77
      conserved miRNAs and 74 novel miRNAs were co-detected in these four samples.
      Eighty-one out of 162 targets of the conserved miRNAs belonged to transcriptional
      regulation (81, 50%), followed by oxidoreductase activity (18, 11%), signal
      transduction (16, 10%) and development (15, 9%). The result showed that miRNA
      156, 393, 396 and 397, with their respective targets, might play key roles in the
      grain filling rate by regulating maize growth, development and environment stress
      response. The result also offered novel insights into the dynamic change of
      miRNAs during the developing process of maize kernels and assisted in the
      understanding of how miRNAs are functioning about the grain filling rate.

PMID- 25951056
TI  - The function of the alula in avian flight.
AB  - The alula is a small structure located at the joint between the hand-wing and arm
      wing of birds and is known to be used in slow flight with high angles of attack
      such as landing. It is assumed to function similarly to a leading-edge slat that
      increases lift and delays stall. However, in spite of its universal presence in
      flying birds and the wide acceptance of stall delay as its main function, how the
      alula delays the stall and aids the flight of birds remains unclear. Here, we
      investigated the function of alula on the aerodynamic performance of avian wings
      based on data from flight tasks and wind-tunnel experiments. With the alula, the
      birds performed steeper descending flights with greater changes in body
      orientation. Force measurements revealed that the alula increases the lift and
      often delays the stall. Digital particle image velocimetry showed that these
      effects are caused by the streamwise vortex, formed at the tip of the alula, that
      induces strong downwash and suppresses the flow separation over the wing surface.
      This is the first experimental evidence that the alula functions as a vortex
      generator that increases the lift force and enhances manoeuvrability in flights
      at high angles of attack. 

PMID- 25951057
TI  - Iminolactones from Schizophyllum commune.
AB  - Schizines A (1) and B (2), the first naturally occurring iminolactones (3,6
      dihydro-2H-1,4-oxazin-2-one derivatives) to be reported, have been isolated from
      the fruiting bodies of Schizophyllym commune. In principle the 2-oxazinone moiety
      might have been formed by a reaction between the amino acid phenylalanine or
      tryptophan and an 2alpha-hydroxy-1-ketomarasmone. The alkaloids are unusual in
      that the carboxyl group of the amino acid precursor is preserved during the
      biosynthesis. The compounds showed some inhibition of the growth of cancer cells.

PMID- 25951059
TI  - Ligand-controlled regiodivergent Cu-catalyzed aminoboration of unactivated
      terminal alkenes.
AB  - A ligand-controlled regiodivergent Cu-catalyzed aminoboration of unactivated
      terminal alkenes with diboron reagents and hydroxylamines has been developed. The
      xantphos-ligated CuCl complex guides the boron and amino groups to the terminal
      and internal positions, respectively. On the other hand, the opposite
      regioisomers are selectively obtained under the N-heterocyclic carbene-based
      IPrCuBr catalysis. The two Cu catalysts can readily transform simple and abundant
      terminal alkenes into highly valuable beta-borylalkylamines regiodivergently. 

PMID- 25951058
TI  - Scaling disturbance instead of richness to better understand anthropogenic
      impacts on biodiversity.
AB  - A primary impediment to understanding how species diversity and anthropogenic
      disturbance are related is that both diversity and disturbance can depend on the
      scales at which they are sampled. While the scale dependence of diversity
      estimation has received substantial attention, the scale dependence of
      disturbance estimation has been essentially overlooked. Here, we break from
      conventional examination of the diversity-disturbance relationship by holding the
      area over which species richness is estimated constant and instead manipulating
      the area over which human disturbance is measured. In the boreal forest ecoregion
      of Alberta, Canada, we test the dependence of species richness on disturbance
      scale, the scale-dependence of the intermediate disturbance hypothesis, and the
      consistency of these patterns in native versus exotic species and among human
      disturbance types. We related field observed species richness in 1 ha surveys of
      372 boreal vascular plant communities to remotely sensed measures of human
      disturbance extent at two survey scales: local (1 ha) and landscape (18 km2).
      Supporting the intermediate disturbance hypothesis, species richness-disturbance
      relationships were quadratic at both local and landscape scales of disturbance
      measurement. This suggests the shape of richness-disturbance relationships is
      independent of the scale at which disturbance is assessed, despite that local
      diversity is influenced by disturbance at different scales by different
      mechanisms, such as direct removal of individuals (local) or indirect alteration
      of propagule supply (landscape). By contrast, predictions of species richness did
      depend on scale of disturbance measurement: with high local disturbance richness
      was double that under high landscape disturbance. 

PMID- 25951060
TI  - Diagnostic value of osteopontin in ovarian cancer: a meta-analysis and systematic
      review.
AB  - AIMS: Osteopontin (OPN) plays an important role in many physiological and
      pathological processes (wound healing, inflammation, immune response, and
      tumorigenesis). This meta-analysis assessed the diagnostic value of osteopontin
      in ovarian cancer. METHODS AND RESULTS: Searches in Embase and PubMed were
      conducted, in order to identify eligible studies on osteopontin expression and
      its diagnostic value in ovarian cancer. The revised Quality Assessment for
      Studies of Diagnostic Accuracy (QUADAS-2) tool was applied to examine the quality
      of these studies and the overall osteopontin diagnostic accuracy in ovarian
      cancer was pooled using the bivariate model. The publication bias was assessed
      using funnel plots and Deek's test. This search methodology resulted in 13
      studies with a total of 839 ovarian cancer patients and 1439 controls in this
      meta-analysis. The overall osteopontin diagnostic sensitivity and specificity of
      ovarian cancer were 0.66 (95% CI, 0.51-0.78) and 0.88 (95% CI, 0.78-0.93),
      respectively. The area under summary receiver operating characteristic (sROC)
      curves (AUC) was 0.85 (95%CI, 0.81-0.88). There was no significant publication
      bias observed across the eligible studies. However, a major design deficiency of
      the eligible studies is the issue of subject selection bias. CONCLUSIONS:
      Osteopontin could be a useful biomarker in diagnosis of ovarian cancer. Due to
      the design deficits of the eligible studies, a future study with a larger sample
      size and better design is needed to rigorously confirm the diagnostic potential
      of osteopontin in ovarian cancer.

PMID- 25951064
TI  - NODding off in acute kidney injury with progranulin?
AB  - Zhou et al. identify progranulin (PGRN) as a protective mediator that limits
      inflammation in murine models of acute kidney injury (AKI) and reduces its
      severity. Deficiency of PGRN was associated with increased inflammation and
      increased injury in ischemic and nephrotoxic models of AKI. Exogenous PGRN
      reduced AKI even when administered after AKI was established. Interference in
      NOD2 pathways is suggested as a possible mechanism for protection. PGRN-based
      therapeutics might have application in the treatment or prevention of AKI. 

PMID- 25951065
TI  - Telling the tiger by its stripes: mapping the genomics of kidney graft tolerance
      in real time.
AB  - Though the majority of kidney allografts are eventually lost to the process of
      chronic rejection, there are instances when kidney function is maintained after
      patients have stopped their immunosuppression. Baron and colleagues have examined
      the blood gene signature of patients with spontaneous kidney tolerance and
      identified a series of genes that they suggest define kidney graft acceptance.
      This exciting development provides a potential list of biomarkers defining
      immunological tolerance in humans. 

PMID- 25951061
TI  - Global transcriptome analysis reveals small RNAs affecting Neisseria meningitidis
      bacteremia.
AB  - Most bacterial small RNAs (sRNAs) are post-transcriptional regulators involved in
      adaptive responses, controlling gene expression by modulating translation or
      stability of their target mRNAs often in concert with the RNA chaperone Hfq.
      Neisseria meningitides, the leading cause of bacterial meningitis, is able to
      adapt to different host niches during human infection. However, only a few sRNAs
      and their functions have been fully described to date. Recently, transcriptional
      expression profiling of N. meningitides in human blood ex vivo revealed 91
      differentially expressed putative sRNAs. Here we expanded this analysis by
      performing a global transcriptome study after exposure of N. meningitides to
      physiologically relevant stress signals (e.g. heat shock, oxidative stress, iron
      and carbon source limitation). and we identified putative sRNAs that were
      differentially expressed in vitro. A set of 98 putative sRNAs was obtained by
      analyzing transcriptome data and 8 new sRNAs were validated, both by Northern
      blot and by primer extension techniques. Deletion of selected sRNAs caused
      attenuation of N. meningitides infection in the in vivo infant rat model, leading
      to the identification of the first sRNAs influencing meningococcal bacteremia.
      Further analysis indicated that one of the sRNAs affecting bacteremia responded
      to carbon source availability through repression by a GntR-like transcriptional
      regulator. Both the sRNA and the GntR-like regulator are implicated in the
      control of gene expression from a common network involved in energy metabolism. 

PMID- 25951066
TI  - Is it time to tip your glass to prevent CKD?
AB  - Chronic kidney disease (CKD) is a major global medical and public health
      challenge. On the basis primarily of a modest number of prospective
      epidemiological studies, it appears that alcohol consumption reduces the risk of
      CKD in the general population. Our understanding of the potential benefits of
      alcohol consumption with regard to CKD is likely to evolve in the future and will
      be informed primarily by observational epidemiological studies. 

PMID- 25951067
TI  - 'How long have I got doctor?' The development and validation of a new prognostic
      model.
AB  - In the current issue of Kidney International, Floege et al report the development
      and external validation of a prognostic score for patients starting
      haemodialysis. The model performs well and appears robust in various sub-groups
      and in external validation. This commentary takes a systematic approach to
      considering the generalisability of the results and applicability of the
      prognostic score to wider clinical practice. 

PMID- 25951068
TI  - Managing atypical hemolytic uremic syndrome: chapter 2.
AB  - Licht et al. present the 2-year follow-up data of the landmark trials studying
      the efficacy of eculizumab in the treatment of atypical hemolytic uremic syndrome
      (aHUS). They report sustained improvements in hematologic parameters, continued
      safety, and additional improvements in kidney function with extended treatment.
      This report adds a layer of comfort to our care of patients with this rare
      disease; however, it is unlikely to be the final chapter in the treatment of
      aHUS. 

PMID- 25951069
TI  - Inverse relationship between soluble urokinase receptors and estimated glomerular
      filtration rate: a role for IL-2?

PMID- 25951070
TI  - The value of ferric citrate, an iron-containing phosphate binder, might be
      different between Japan and the United States.

PMID- 25951071
TI  - The authors reply.

PMID- 25951073
TI  - Multiple osteoporotic fractures in a patient with CKD stage G3b.

PMID- 25951072
TI  - The authors reply.

PMID- 25951074
TI  - Amputation of the peritoneal dialysis catheter in the abdominal cavity.

PMID- 25951075
TI  - The Case | Ectopic calcifications in a child.

PMID- 25951076
TI  - Closure of the rectal defect after transanal minimally invasive surgery: a word
      of caution.

PMID- 25951078
TI  - "The Dose Makes the Poison": Informing Consumers About the Scientific Risk
      Assessment of Food Additives.
AB  - Intensive risk assessment is required before the approval of food additives.
      During this process, based on the toxicological principle of "the dose makes the
      poison,? maximum usage doses are assessed. However, most consumers are not aware
      of these efforts to ensure the safety of food additives and are therefore
      sceptical, even though food additives bring certain benefits to consumers. This
      study investigated the effect of a short video, which explains the scientific
      risk assessment and regulation of food additives, on consumers' perceptions and
      acceptance of food additives. The primary goal of this study was to inform
      consumers and enable them to construct their own risk-benefit assessment and make
      informed decisions about food additives. The secondary goal was to investigate
      whether people have different perceptions of food additives of artificial (i.e.,
      aspartame) or natural origin (i.e., steviolglycoside). To attain these research
      goals, an online experiment was conducted on 185 Swiss consumers. Participants
      were randomly assigned to either the experimental group, which was shown a video
      about the scientific risk assessment of food additives, or the control group,
      which was shown a video about a topic irrelevant to the study. After watching the
      video, the respondents knew significantly more, expressed more positive thoughts
      and feelings, had less risk perception, and more acceptance than prior to
      watching the video. Thus, it appears that informing consumers about complex food
      safety topics, such as the scientific risk assessment of food additives, is
      possible, and using a carefully developed information video is a successful
      strategy for informing consumers. 

PMID- 25951077
TI  - An empirical investigation of dance addiction.
AB  - Although recreational dancing is associated with increased physical and
      psychological well-being, little is known about the harmful effects of excessive
      dancing. The aim of the present study was to explore the psychopathological
      factors associated with dance addiction. The sample comprised 447 salsa and
      ballroom dancers (68% female, mean age: 32.8 years) who danced recreationally at
      least once a week. The Exercise Addiction Inventory (Terry, Szabo, & Griffiths,
      2004) was adapted for dance (Dance Addiction Inventory, DAI). Motivation, general
      mental health (BSI-GSI, and Mental Health Continuum), borderline personality
      disorder, eating disorder symptoms, and dance motives were also assessed. Five
      latent classes were explored based on addiction symptoms with 11% of participants
      belonging to the most problematic class. DAI was positively associated with
      psychiatric distress, borderline personality and eating disorder symptoms.
      Hierarchical linear regression model indicated that Intensity (beta=0.22),
      borderline (beta=0.08), eating disorder (beta=0.11) symptoms, as well as Escapism
      (beta=0.47) and Mood Enhancement (beta=0.15) (as motivational factors) together
      explained 42% of DAI scores. Dance addiction as assessed with the Dance Addiction
      Inventory is associated with indicators of mild psychopathology and therefore
      warrants further research. 

PMID- 25951079
TI  - Hepatic flares promote rapid decline of serum hepatitis B surface antigen (HBsAg)
      in patients with HBsAg seroclearance: A long-term follow-up study.
AB  - AIM: Serum hepatitis B surface antigen (HBsAg) seroclearance is one of the
      ultimate goals of management of chronic hepatitis B. We investigated the kinetics
      of serum HBsAg before HBsAg seroclearance in patients with chronic hepatitis B.
      METHODS: We retrospectively analyzed 392 Japanese chronic hepatitis B patients
      who had been followed for 5 years or more between 1980 and 2000. Serum HBsAg
      levels were measured annually using chemiluminescent enzyme immunoassay. RESULTS:
      During a median follow up of 14 years, 50 patients demonstrated HBsAg
      seroclearance (annual incidence rate, 0.91%). Multivariate analysis with baseline
      characteristics revealed that HBsAg of less than 3.3 log IU/mL (hazard ratio
      [HR], 2.22; P = 0.008) and treatment with nucleoside/nucleotide analog (HR, 0.12;
      P = 0.001) were independent predictive factors for seroclearance. The median
      HBsAg levels at 20, 10, 5, 3 and 1 year prior to seroclearance were 3.89, 2.84,
      1.84, 0.78 and -1.10 log IU/mL, respectively. The rapid decline group, comprising
      patients who achieved HBsAg seroclearance within 5 years after confirmed HBsAg
      levels of 2 log IU/mL, demonstrated: (i) high alanine aminotransferase (ALT)
      levels; and (ii) a low frequency of liver cirrhosis progression. A significant
      reduction in annual HBsAg levels was found in years marked by at least one ALT
      flare (ALT >=200 IU/L) (flare [+], n = 62) than in those without (flare [-], n =
      323) (0.29 vs 0.17 log IU/mL/year, P = 0.003). CONCLUSION: Hepatic flares
      promoted rapid declines and greater annual reductions of HBsAg levels in patients
      with HBsAg seroclearance.

PMID- 25951080
TI  - Cerebral palsy research funding from the National Institutes of Health, 2001 to
      2013.
AB  - AIM: Cerebral palsy (CP) is a poorly understood disorder with no cure. We
      determined the landscape of National Institutes of Health (NIH) funding for CP
      related research. METHOD: We searched NIH databases Research Portfolio Online
      Reporting Tools Expenditures and Results, and Research, Condition, and Disease
      Categorization for keywords 'cerebral palsy' among all NIH-funded studies, 2001
      to 2013. We classified grants by type and area of study. RESULTS: NIH funding,
      averaging $30 million per year, supported clinical ($215 million), basic ($187
      million), and translational ($26.3 million) CP-related research. Clinical
      intervention studies comprised 19% of funding, and focused on treatments ($60.3
      million), early parent intervention ($2.7 million), and CP prevention ($2.5
      million). Among grants that specified gestational age, more funds were devoted to
      preterm ($166 million) than term infants ($15 million). CP in adulthood was the
      main focus of 4% of all funding. Annual NIH funding for CP increased steadily
      over the study period from $3.6 to $66.7 million. However, funding for clinical
      intervention studies peaked in 2008, and has since decreased. INTERPRETATION:
      Additional research funds are needed to improve the treatment and prevention of
      CP. Topics that have been relatively underfunded include clinical interventions,
      prevention, and term infants and adults with CP.

PMID- 25951081
TI  - What Glues a Homodimer Together: Systematic Analysis of the Stabilizing Effect of
      an Aromatic Hot Spot in the Protein-Protein Interface of the tRNA-Modifying
      Enzyme Tgt.
AB  - Shigella bacteria constitute the causative agent of bacillary dysentery, an acute
      inflammatory disease causing the death of more than one million humans per year.
      A null mutation in the tgt gene encoding the tRNA-modifying enzyme tRNA-guanine
      transglycosylase (Tgt) was found to drastically decrease the pathogenicity of
      Shigella bacteria, suggesting the use of Tgt as putative target for selective
      antibiotics. The enzyme is only functionally active as a homodimer; thus,
      interference with the formation of its protein-protein interface is an attractive
      opportunity for therapeutic intervention. To better understand the driving forces
      responsible for the assembly, stability, and formation of the homodimer, we
      studied the properties of the residues that establish the dimer interface in
      detail. We performed site-directed mutagenesis and controlled shifts in the
      monomer/dimer equilibrium ratio in solution in a concentration-dependent manner
      by native mass spectrometry and used crystal structure analysis to elucidate the
      geometrical modulations resulting from mutational variations. The wild-type
      enzyme exhibits nearly exclusive dimer geometry. A patch of four aromatic amino
      acids, embedded into a ring of hydrophobic residues and further stabilized by a
      network of H-bonds, is essential for the stability of the dimer's contact.
      Accordingly, any perturbance in the constitution of this aromatic patch by
      nonaromatic residues reduces dimer stability significantly, with some of these
      exchanges resulting in a nearly exclusively monomeric state. Apart from the
      aromatic hot spot, the interface comprises an extended loop-helix motif that
      exhibits remarkable flexibility. In the destabilized mutated variants, the loop
      helix motif adopts deviating conformations in the interface region, and a number
      of water molecules, penetrating into the interface, are observed. 

PMID- 25951082
TI  - 2015 European guidelines for the management of partners of persons with sexually
      transmitted infections.
AB  - BACKGROUND: Partner management is the process of identifying the contacts of a
      person infected by a sexually transmitted infection (STI) and referral to a
      health care provider for appropriate management. It represents a public health
      activity. METHODS: This guideline is produced by the IUSTI European Guideline
      Editorial Board and EDF Guideline Committee. RESULTS: It provides recommendations
      concerning the infections that require partner management, the lookback periods
      for this STI and the main steps to follow for partner management (offering
      support to patients, notifying partners, identification of contacts). Partner
      management is voluntary and needs to be performed with respect to human rights,
      social, cultural and religious behaviours. CONCLUSIONS: In European countries,
      there are different approaches to the partner management; some common type of
      actions can enhance the fight against STI.

PMID- 25951084
TI  - BODIPY-based azamacrocyclic ensemble for selective fluorescence detection and
      quantification of homocysteine in biological applications.
AB  - Considering the significant role of plasma homocysteine in physiological
      processes, two ensembles (F465-Cu(2+) and F508-Cu(2+)) were constructed based on
      a BODIPY (4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene)
      scaffold conjugated with an azamacrocyclic (1,4,7-triazacyclononane and 1,4,7,10
      tetraazacyclododecane) Cu(2+) complex. The results of this effort demonstrated
      that the F465-Cu(2+) ensemble could be employed to detect homocysteine in the
      presence of other biologically relevant species, including cysteine and
      glutathione, under physiological conditions with high selectivity and sensitivity
      in the turn-on fluorescence mode, while the F508-Cu(2+) ensemble showed no
      fluorescence responses toward biothiols. A possible mechanism for this
      homocysteine-specific specificity involving the formation of a homocysteine
      induced six-membered ring sandwich structure was proposed and confirmed for the
      first time by time-dependent fluorescence spectra, ESI-MS and EPR. The detection
      limit of homocysteine in deproteinized human serum was calculated to be 241.4 nM
      with a linear range of 0-90.0 MUM and the detection limit of F465 for Cu(2+) is
      74.7 nM with a linear range of 0-6.0 MUM (F508, 80.2 nM, 0-7.0 MUM). We have
      demonstrated the application of the F465-Cu(2+) ensemble for detecting
      homocysteine in human serum and monitoring the activity of cystathionine beta
      synthase in vitro.

PMID- 25951083
TI  - Transcriptome-wide identification of salt-responsive members of the WRKY gene
      family in Gossypium aridum.
AB  - WRKY transcription factors are plant-specific, zinc finger-type transcription
      factors. The WRKY superfamily is involved in abiotic stress responses in many
      crops including cotton, a major fiber crop that is widely cultivated and consumed
      throughout the world. Salinity is an important abiotic stress that results in
      considerable yield losses. In this study, we identified 109 WRKY genes (GarWRKYs)
      in a salt-tolerant wild cotton species Gossypium aridum from transcriptome
      sequencing data to elucidate the roles of these factors in cotton salt tolerance.
      According to their structural features, the predicted members were divided into
      three groups (Groups I-III), as previously described for Arabidopsis.
      Furthermore, 28 salt-responsive GarWRKY genes were identified from digital gene
      expression data and subjected to real-time quantitative RT-PCR analysis. The
      expression patterns of most GarWRKY genes revealed by this analysis are in good
      agreement with those revealed by RNA-Seq analysis. RT-PCR analysis revealed that
      27 GarWRKY genes were expressed in roots and one was exclusively expressed in
      roots. Analysis of gene orthology and motif compositions indicated that WRKY
      members from Arabidopsis, rice and soybean generally shared the similar motifs
      within the same subgroup, suggesting they have the similar function.
      Overexpression-GarWRKY17 and -GarWRKY104 in Arabidopsis revealed that they could
      positively regulate salt tolerance of transgenic Arabidopsis during different
      development stages. The comprehensive data generated in this study provide a
      platform for elucidating the functions of WRKY transcription factors in salt
      tolerance of G. aridum. In addition, GarWRKYs related to salt tolerance
      identified in this study will be potential candidates for genetic improvement of
      cultivated cotton salt stress tolerance. 

PMID- 25951085
TI  - An improved functional assay for rapid detection of marine toxins, saxitoxin and
      brevetoxin using a portable cardiomyocyte-based potential biosensor.
AB  - Saxitoxin (STX) and brevetoxin (PbTX-2), which are produced by marine
      dinoflagellates, are highly-toxic marine toxins targeting separate sites of the
      alpha subunit of voltage-dependent sodium channels (VDSCs). In this work, a
      portable cardiomyocyte-based potential biosensor is designed for rapid detection
      of STX and PbTX-2. This potential biosensor is constructed by cardiomyocyte and
      microelectrode array (MEA) with a label-free and real-time wireless 8-channel
      recording system which can dynamically monitor the multisite electrical activity
      of cardiomyocyte network. The recording signal parameters, spike amplitude,
      firing rate and 50% of spike potential duration (SPD50) extracted from
      extracelluar field potential (EFP) signals of the potential biosensor is analyzed
      to quantitatively evaluate toxicological risk of STX and PbTX-2. Firing rate of
      biosensor signals presents high sensitivity to STX with the detection limit of
      0.35 ng/ml within 5 min. SPD50 shows high sensitivity to PbTX-2 with the
      detection limit of 1.55 ng/ml within 5 min. Based on the multi-parameter
      analysis, cardiomyocyte-based potential biosensor will be a promising tool for
      rapid detection of these two toxins.

PMID- 25951086
TI  - How does the dinoflagellate parasite Hematodinium outsmart the immune system of
      its crustacean hosts?

PMID- 25951087
TI  - Is occupation a good predictor of self-rated health in China?
AB  - BACKGROUND: China's rapidly changing economic landscape has led to widening
      social inequalities. Occupational status in terms of occupational type and
      prestige may reflect these socio-structural shifts of social position and be more
      predictive of self-rated health status than income and education, which may only
      reflect more gradual acquisitions of social status over time. The goals of this
      study were to understand the role of occupational status in predicting self-rated
      health, which is well known to be associated with long-term mortality, as well as
      compare the occupational status to the other major socioeconomic indicators of
      income and education. METHODS: Data from the 2010 baseline surveys of the China
      Family Panel Studies, which utilized multi-stage probability sampling with
      implicit stratification was used. Logistic regression was used to examine the
      relationship of various socioeconomic indicators (i.e. occupational status,
      income, and education) with self-rated health as the primary outcome of interest.
      A series of models considered the associations of occupational category or
      occupational prestige with self-rated health. RESULTS: The final sample consisted
      of 14,367 employed adults aged 18-60, which was nationally representative of
      working adults in China. We found that occupation was not a major predictor of
      self-rated health in China when age, ethnicity, location, marital status,
      physical and mental health status were controlled for, with the exception of
      women working in lower grade management and professional jobs (OR = 1.82, 95% CI:
      1.03-3.22). In comparison, income followed by education exhibited greater
      association with self-rated health. The highest income group had the least
      probability to report poor health (In men: OR = 0.30, 95% CI: 0.21-0.43. In
      women: OR = 0.44, 95% CI: 0.26-0.73). People educated with junior high school had
      better self-rated health than those with primary and below education level (In
      men: OR = 0.62, 95% CI: 0.50-0.75. In women: OR = 0.53, 95% CI: 0.42-0.68).
      Income, education and occupation were correlated with each other. CONCLUSIONS:
      Within the context of rapid societal changes in China, income and its
      implications for greater healthcare access and benefits had the greatest
      association with self-rated health followed by education. Occupational status was
      not associated. Occupational categories and prestige should be better adapted to
      reflect China's unique sociopolitical and historical context.

PMID- 25951088
TI  - Children's recognition of pride.
AB  - The purpose of this experiment was to examine when children identify their own
      experience as one of pride after they complete a difficult and competitive task
      (i.e., race a confederate in building a tower of blocks). A sample of 144
      children between 3 and 6 years of age participated in one of three conditions.
      Children were told to try to build a tower of blocks taller than a confederate's
      tower (exceed standard) or tried and failed to build a tower of blocks taller
      than the confederate's tower (fail standard), or children were asked to build a
      tower of blocks alongside a confederate (no standard). Results revealed a
      developmental progression of recognizing pride in which children first began
      showing nonverbal behaviors that were reliably coded as conveying pride at around
      4 years of age. Children began to apply the label/term "pride" to a photograph
      conveying pride in another peer at around 4 years of age and recognized their own
      experience as one of pride following a competitive task at around 5 years of age.

PMID- 25951089
TI  - Klebsiella pneumoniae and the pyogenic liver abscess: implications and
      association of the presence of rpmA genes and expression of hypermucoviscosity.

PMID- 25951090
TI  - Lack of Standardization in the Use of the Glasgow Coma Scale: Results of
      International Surveys.
AB  - The Glasgow Coma Scale (GCS) was introduced 40 years ago and has received world
      wide acceptance. The GCS rates eye, motor, and verbal responses to assess the
      level of consciousness. Concerns have been expressed with regard to reliability
      and consistency of assessments. We considered that lack of standardization in
      application techniques and reporting of the GCS may have contributed to these
      concerns, and aimed to assess current procedures in its use. Questionnaire-based
      assessments were conducted by an online survey and during neurosurgical training
      courses. Overall, 616 participants were recruited, representing 48 countries and
      including physicians and nurses from different disciplines. Use of the GCS was
      reported by nearly all participants for assessment of patients with traumatic
      brain injury, but not for all patients with a reduced level of consciousness from
      other causes (78%). Major differences were found regarding the type of stimulus
      applied when patients do not obey commands: Nail bed pressure, supraorbital
      pressure, trapezius or pectoralis pinch, and sternal rub were all frequently
      used, whereas 25% of responders reported to never use a peripheral stimulus.
      Strategies for reporting the GCS varied greatly, and 35% of participants limited
      the reporting to a summary score. Moreover, different approaches were used when
      one of the components could not be assessed. Overall, the surveys have identified
      a general lack of standardization in assessment and reporting of the GCS. The
      results illustrate the need for continued education to improve reliability of
      assessments through guidance to a standard approach. 

PMID- 25951091
TI  - Preparation and X-ray Structural Study of Dibenziodolium Derivatives.
AB  - New experimental procedures for the preparation of dibenziodolium salts by
      oxidative cyclization of 2-iodobiphenyl in the presence of appropriate strong
      acids are described. Particularly useful is a convenient one-pot synthesis of
      dibenziodolium hydrogen sulfate from 2-iodobiphenyl using Oxone as an inexpensive
      and environmentally safe oxidant. Dibenziodolium hydrogen sulfate,
      bis(triflyl)imidate, or triflate can be readily converted to various other
      dibenziodolium derivatives (chloride, bromide, thiocyanate, azide, cyanide,
      phenylsulfinate) by anion exchange. Structures of key products have been
      established by single-crystal X-ray diffraction analysis. Particularly
      interesting is the X-ray structure of dibenziodolium thiocyanate, which
      represents the first example of a structurally characterized hypervalent iodine
      compound with a relatively short iodine-sulfur secondary bond distance. 

PMID- 25951092
TI  - Extraordinary benefits of an ordinary silicone tube.

PMID- 25951093
TI  - Definitions of disease: should possible and probable idiopathic pulmonary
      fibrosis be enrolled in treatment trials?
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic, fibrosing interstitial lung
      disease of unknown etiology characterized by progressive lung scarring and a
      median survival of 3-5 years from the time of diagnosis. The most recent
      consensus guidelines adopt a diagnostic process that characterizes patients as
      having a final diagnosis of IPF, probable IPF, or possible IPF determined from a
      combination of the clinical context and specific chest imaging and histologic
      disease patterns. Based on currently available data, the enrollment criteria for
      treatment trials could be expanded to include not only patients with IPF but also
      those with probable and possible IPF without adversely affecting trial design or
      outcomes. 

PMID- 25951094
TI  - Endobronchial ultrasound-guided transbronchial biopsy with or without a guide
      sheath for diagnosis of lung cancer.
AB  - BACKGROUND: Endobronchial ultrasound-guided transbronchial biopsy with a guide
      sheath (EBUS-GS) is widely used for diagnosing lung cancers; however, the
      diagnostic yield varies widely. This study aimed to assess the efficiency of EBUS
      GS. METHODS: We retrospectively evaluated the results of 110 patients who
      underwent transbronchial biopsy (TBB) for diagnosis of peripheral lung cancer.
      Bronchoscopy with and without EBUS-GS was performed in 60 (group A) and 50
      patients (group B), respectively; their medical records were examined, and
      results from the two groups were compared by using the unpaired Student t-test.
      RESULTS: The diagnostic sensitivity for lung cancer was 83.3% in group A and 68%
      in group B (P=0.066) while using at least one of the following procedures: TBB,
      cytological brushing, and bronchial washing. The diagnostic sensitivity for
      lesions >=20mm was 86.4% in group A and 76.7% in group B (P=0.263). Moreover, the
      diagnostic sensitivity for lesions 10-20mm was 60% in group A and 14.2% in group
      B (P=0.0004); the diagnostic sensitivity with TBB alone was 63.3% in group A and
      44% in group B (P=0.043). The diagnostic sensitivity with TBB alone for lesions
      >=20mm was 70.2% in group A and 44.8% in group B (P=0.051). Moreover, the
      diagnostic sensitivity for lesions 10-20mm in size was 45% in group A and 14.2%
      in group B with TBB alone (P=0.115). CONCLUSION: EBUS-GS with TBB, brushing, and
      bronchial washing is effective in diagnosing lung cancers sized <20mm.

PMID- 25951096
TI  - Superiority of respiratory failure risk index in prediction of postoperative
      pulmonary complications after digestive surgery in Japanese patients.
AB  - BACKGROUND: Several multifactorial risk indexes have been proposed by Western
      countries for identifying patients at a high risk of developing postoperative
      pulmonary complications (PPC). However, there is no consensus on how to evaluate
      the risk of PPC and what multifactorial risk index should be adapted for Japanese
      patients. This study aimed at clarifying the utility of risk indexes to predict
      PPC following digestive surgeries in Japanese patients. METHODS: We
      retrospectively analyzed 892 patients who underwent digestive surgeries under
      general anesthesia in Niigata University Medical and Dental Hospital between
      January 2009 and March 2011. PPC was defined as postoperative respiratory failure
      and postoperative pneumonia. We calculated three risk indexes (respiratory
      failure risk index (RFRI), postoperative pneumonia risk index, and PPC risk
      score), and compared them between the PPC group and the non-PPC group. A receiver
      operating characteristic (ROC) curve analysis was employed to compare the
      usefulness of each index. RESULTS: PPC developed in 55 patients (6.2%). All risk
      indexes were significantly higher in the PPC group than the non-PPC group. The
      category classification of the risk scores demonstrated a significant tendency to
      increase the incidence rate of PPC. In the ROC analysis, the area under the curve
      for RFRI was 0.762 (95% CI 0.697-0.826), which was the highest value observed
      among these indexes. CONCLUSIONS: Multifactorial risk indexes are useful tools
      for identifying Japanese patients at a high risk of developing PPC following
      digestive surgeries. Of the risk indexes evaluated in this study, RFRI is
      potentially the most accurate in predicting PPC.

PMID- 25951095
TI  - Do respiratory comorbidities limit the diagnostic usefulness of ultrasound-guided
      needle aspiration for subpleural lesions?
AB  - BACKGROUND: The usefulness of ultrasound-guided needle aspiration for subpleural
      lesions has been reported. However, no reports have evaluated its usefulness and
      safety in patients with respiratory comorbidities such as chronic obstructive
      pulmonary disease (COPD) and interstitial pneumonia (IP), which can increase the
      risk of iatrogenic pneumothorax. In this study, we evaluated the influence of
      chronic respiratory diseases (CRDs) on the usefulness and safety of ultrasound
      guided needle aspiration for subpleural lesions. METHODS: Between January 2000
      and September 2011, we examined 144 patients with intrapulmonary subpleural
      lesions. We retrospectively reviewed clinical data, including lesion size on
      thoracic computed tomography (CT), ultrasound findings, pathological findings
      obtained by ultrasound-guided needle aspiration, final diagnosis, and
      complications. RESULTS: A positive definitive diagnosis was obtained in 74.3% of
      all 144 patients; 84.7% patients with malignant diseases, including lung cancer;
      and 26.9% patients with benign diseases. Of the 144 patients, 64 belonged to the
      CRD group and 80 to the non-CRD group. The former included 31 patients with COPD,
      six with emphysematous changes on thoracic CT, 17 with IP, and 10 with other
      diseases. The positive rate of diagnosis for malignant diseases was 84.7% in the
      CRD group, which was the same as that in the non-CRD group. With regard to
      complications related to ultrasound-guided aspiration, there were only two cases
      of pneumothorax in the CRD group and one in the non-CRD group. CONCLUSION:
      Ultrasound-guided aspiration is safe and useful for subpleural lesions,
      particularly malignant lesions, even in patients with respiratory comorbidities
      such as COPD and IP.

PMID- 25951098
TI  - Risk stratification by the lower limit of normal of FEV1/FVC for postoperative
      outcomes in patients with COPD undergoing thoracic surgery.
AB  - BACKGROUND: Mounting evidence suggests that airway obstruction defined by the
      lower limit of normal (LLN) of forced expiration volume in 1s (FEV1)/forced vital
      capacity (FVC) might be an important predictor of mortality in patients with an
      FEV1/FVC ratio below 0.70. Although better risk stratification for postoperative
      outcomes in patients with chronic obstructive pulmonary disease (COPD) undergoing
      thoracic surgery is warranted, whether an FEV1/FVC ratio below 0.70 but above the
      LLN (i.e., in-between) could identify patients at risk for adverse postoperative
      outcomes has not been fully evaluated. METHODS: To determine the clinical impact
      of this "in-between" group of patients with COPD, we evaluated whether
      classification of the in-between group and the COPD group with FEV1/FVC ratios
      below 0.70 and below the LLN could provide more accurate risk stratification for
      postoperative outcomes in COPD patients undergoing thoracic surgery. RESULTS: The
      criterion of LLN classified 302 patients with an FEV1/FVC ratio below 0.70 into
      either the in-between group (124 cases) or the COPD group (178 cases). The COPD
      group showed a 3-fold increase in prolonged oxygen therapy (POT) and a 50%
      increase in prolonged postoperative stay (PPS), as compared with the in-between
      group, with an adjusted odds ratio of 3.068 (95% confidence interval: 1.806
      5.213) for POT. CONCLUSIONS: Based on the finding that the in-between group could
      independently identify patients at risk for adverse postoperative outcomes, LLN
      assessment of the FEV1/FVC ratio might provide more accurate risk stratification
      in COPD patients undergoing thoracic surgery.

PMID- 25951097
TI  - Low arterial blood oxygenation is associated with calcification of the coronary
      arteries in patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Cigarette smoking is a well-known major cause of both chronic
      obstructive pulmonary disease (COPD) and atherosclerosis. However, few studies
      have investigated the correlation between COPD and coronary atherosclerosis.
      METHODS: We recruited 54 patients with stable COPD (51 men, 3 women) but without
      angina symptoms. Arterial blood gas analyses were performed, pulmonary function
      was assessed, and calcification of the coronary arteries was evaluated by
      computed tomography (CT). RESULTS: Calcification of the coronary arteries was
      noted in 25 patients. There were no significant differences in age, body mass
      index, respiratory function, and levels of low-density lipoprotein cholesterol,
      hemoglobin A1c, glucose, or C-reactive protein between patients with or without
      calcification of the coronary arteries. Arterial blood oxygenation was
      significantly lower in patients with calcification of the coronary arteries. On
      both univariate and multivariate analyses, low arterial blood oxygenation was an
      independent risk factor for calcification of the coronary arteries. CONCLUSIONS:
      In patients with COPD, low arterial blood oxygenation was strongly associated
      with calcification of the coronary arteries and may be a significant predictor of
      cardiovascular disease.

PMID- 25951099
TI  - Ventilator-associated pneumonia caused by colistin-resistant KPC-producing
      Klebsiella pneumoniae: a case report and literature review.
AB  - Klebsiella pneumoniae producing KPC-type carbapenemase causes severe nosocomial
      infection at a high mortality rate. Nosocomial pneumonia in particular is
      associated with high mortality, likely due to the unfavorable pulmonary
      pharmacokinetics of the antibiotics used against this agent. Therefore, early and
      accurate microbiological identification and susceptibility evaluation are crucial
      in order to optimize antibiotic therapy. We report a case of ventilator
      associated pneumonia caused by colistin-resistant K. pneumoniae producing KPC
      type carbapenemase treated using a carbapenem-sparing therapy and tailored
      according to the serum procalcitonin concentration in order to limit the duration
      of antibiotic therapy. 

PMID- 25951100
TI  - Case series of lung abscesses following flexible bronchoscopy.

PMID- 25951101
TI  - Lung cancer with cavitation: a distinct subgroup of non-small cell lung cancer
      associated with poor overall survival.

PMID- 25951102
TI  - Photoactive high explosives: linear and nonlinear photochemistry of petrin
      tetrazine chloride.
AB  - Pentaerythritol tetranitrate (PETN), a high explosive, initiates with traditional
      shock and thermal mechanisms. In this study, the tetrazine-substituted derivative
      of PETN, pentaerythritol trinitrate chlorotetrazine (PetrinTzCl), is being
      investigated for a photochemical initiation mechanism that could allow control
      over the chemistry contributing to decomposition leading to initiation.
      PetrinTzCl exhibits a photochemical quantum yield (QYPC) at 532 nm not evident
      with PETN. Using static spectroscopic methods, we observe energy absorption on
      the tetrazine (Tz) ring that results in photodissociation yielding N2, Cl-CN, and
      Petrin-CN as the major photoproducts. The QYPC was enhanced with increasing
      irradiation intensity. Experiment and theoretical calculations imply this
      excitation mechanism follows sequential photon absorption. Dynamic simulations
      demonstrate that the relaxation mechanism leading to the observed photochemistry
      in PetrinTzCl is due to vibrational excitation during internal conversion.
      PetrinTzCl's single photon stability and intensity dependence suggest this
      material could be stable in ambient lighting, yet possible to initiate with short
      pulsed lasers. 

PMID- 25951104
TI  - Glandular Lesions of the Cervix in Clinical Practice: A Cytology, Histology, and
      Human Papillomavirus Correlation Study From 2 Institutions.
AB  - CONTEXT: The Papanicolaou (Pap) test has indisputably decreased cervical cancer
      mortality, as rates have declined by up to 80% in the United States since its
      implementation. However, the Pap test is considered less sensitive for detecting
      glandular lesions than for detecting those of squamous origin. Some studies have
      even suggested an increasing incidence of cervical adenocarcinoma, which may be a
      consequence of a relatively reduced ability to detect glandular lesions with
      cervical cancer screening techniques. OBJECTIVE: To evaluate the detection rate
      of glandular lesions with screening techniques currently used for cervical cancer
      screening and to provide insight as to which techniques are most efficacious in
      our study population. DESIGN: We retrospectively reviewed any available cytology,
      human papillomavirus (HPV), and histologic malignancy data in patients diagnosed
      with adenocarcinoma in situ and adenocarcinoma from 2 geographically and
      socioeconomically disparate hospital systems. Identified patients having had a
      negative/unsatisfactory Pap test within 5 years of adenocarcinoma in situ or
      adenocarcinoma tissue diagnosis were considered Pap test screening failures.
      Patients with negative HPV tests on cytology samples were considered HPV
      screening failures. RESULTS: One hundred thirty cases were identified (age range,
      22-93 years); 39 (30%) had no Pap history in our files. Eight of 91 remaining
      cases (8.8%) were screening failures. The detected sensitivity for identifying
      adenocarcinoma in situ/adenocarcinoma in this study was 91.2% by cytology alone
      and 92.3% when incorporating HPV testing. The most common cytologic diagnosis was
      atypical glandular cells (25 cases), and those diagnosed with adenocarcinoma were
      7.4 years older than those diagnosed with adenocarcinoma in situ (50.3 versus
      42.9 years). Nine of 24 HPV-tested cases (37.5%) were called atypical squamous
      cell of undetermined significance on cytology. CONCLUSIONS: Our results highlight
      the importance of combined Pap and HPV cotesting. Although the number of cases
      identified is relatively small, our data suggest screening for squamous lesions
      facilitates the recognition of glandular lesions in the cervix. Additionally,
      increased use of combined Pap and HPV cotesting may decrease detection failure
      rates with regard to glandular lesions.

PMID- 25951103
TI  - A critical assessment of vector control for dengue prevention.
AB  - Recently, the Vaccines to Vaccinate (v2V) initiative was reconfigured into the
      Partnership for Dengue Control (PDC), a multi-sponsored and independent
      initiative. This redirection is consistent with the growing consensus among the
      dengue-prevention community that no single intervention will be sufficient to
      control dengue disease. The PDC's expectation is that when an effective dengue
      virus (DENV) vaccine is commercially available, the public health community will
      continue to rely on vector control because the two strategies complement and
      enhance one another. Although the concept of integrated intervention for dengue
      prevention is gaining increasingly broader acceptance, to date, no consensus has
      been reached regarding the details of how and what combination of approaches can
      be most effectively implemented to manage disease. To fill that gap, the PDC
      proposed a three step process: (1) a critical assessment of current vector
      control tools and those under development, (2) outlining a research agenda for
      determining, in a definitive way, what existing tools work best, and (3)
      determining how to combine the best vector control options, which have
      systematically been defined in this process, with DENV vaccines. To address the
      first step, the PDC convened a meeting of international experts during November
      2013 in Washington, DC, to critically assess existing vector control
      interventions and tools under development. This report summarizes those
      deliberations. 

PMID- 25951105
TI  - Kickoff to conflict: a sequence analysis of intra-state conflict-preceding event
      structures.
AB  - While many studies have suggested or assumed that the periods preceding the onset
      of intra-state conflict are similar across time and space, few have empirically
      tested this proposition. Using the Integrated Crisis Early Warning System's
      domestic event data in Asia from 1998-2010, we subject this proposition to
      empirical analysis. We code the similarity of government-rebel interactions in
      sequences preceding the onset of intra-state conflict to those preceding further
      periods of peace using three different metrics: Euclidean, Levenshtein, and
      mutual information. These scores are then used as predictors in a bivariate
      logistic regression to forecast whether we are likely to observe conflict in
      neither, one, or both of the states. We find that our model accurately classifies
      cases where both sequences precede peace, but struggles to distinguish between
      cases in which one sequence escalates to conflict and where both sequences
      escalate to conflict. These findings empirically suggest that generalizable
      patterns exist between event sequences that precede peace. 

PMID- 25951106
TI  - Overexpression of miR-145-5p inhibits proliferation of prostate cancer cells and
      reduces SOX2 expression.
AB  - We aimed to perform functional analysis of miR-145-5p in prostate cancer (PCa)
      cells and to identify targets of miR-145-5p for understanding its role in PCa
      pathogenesis. PC3, DU145, LNCaP PCa, and PNT1a nontumorigenic prostate cell lines
      were utilized for functional analysis of miR-145-5p. Its overexpression caused
      inhibition of proliferation through apoptosis and reduced migration in PCa cells.
      SOX2 expression was significantly decreased in both mRNA and protein level in miR
      145-5p-overexpressed PCa cells. We proposed that miR-145-5p, being an important
      regulator of SOX2, carries a crucial role in PCa tumorigenesis. 

PMID- 25951107
TI  - Marked Genetic Differentiation between Western Iberian and Italic Populations of
      the Olive Fly: Southern France as an Intermediate Area.
AB  - The olive fly, Bactrocera oleae, is the most important pest affecting the olive
      industry, to which it is estimated to cause average annual losses in excess of
      one billion dollars. As with other insects with a wide distribution, it is
      generally accepted that the understanding of B. oleae population structure and
      dynamics is fundamental for the design and implementation of effective monitoring
      and control strategies. However, and despite important advances in the past
      decade, a clear picture of B. oleae's population structure is still lacking. In
      the Mediterranean basin, where more than 95% of olive production is concentrated,
      evidence from several studies suggests the existence of three distinct sub
      populations, but the geographical limits of their distributions, and the level of
      interpenetration and gene flow among them remain ill-characterized. Here we use
      mitochondrial haplotype analysis to show that one of the Mediterranean
      mitochondrial lineages displays geographically correlated substructure and
      demonstrate that Italic populations, though markedly distinct from their Iberian
      and Levantine counterparts are more diverse than previously described. Finally,
      we show that this distinction does not result from extant hypothetical geographic
      limits imposed by the Alps or the Pyrenees nor, more generally, does it result
      from any sharp boundary, as intermixing is observed in a broad area, albeit at
      variable levels. Instead, Bayesian phylogeographic analysis suggests the
      interplay between isolation-mediated differentiation during glacial periods and
      bi-directional dispersal and population intermixing in the interglacials has
      played a major role in shaping current olive fly population structure. 

PMID- 25951108
TI  - Anomalous Plastic Deformation and Sputtering of Ion Irradiated Silicon Nanowires.
AB  - Silicon nanowires of various diameters were irradiated with 100 keV and 300 keV
      Ar(+) ions on a rotatable and heatable stage. Irradiation at elevated
      temperatures above 300  degrees C retains the geometry of the nanostructure and
      sputtering can be gauged accurately. The diameter dependence of the sputtering
      shows a maximum if the ion range matches the nanowire diameter, which is in good
      agreement with Monte Carlo simulations based on binary collisions. Nanowires
      irradiated at room temperature, however, amorphize and deform plastically. So
      far, plastic deformation has not been observed in bulk silicon at such low ion
      energies. The magnitude and direction of the deformation is independent of the
      ion-beam direction and cannot be explained with mass-transport in a binary
      collision cascade but only by collective movement of atoms in the collision
      cascade with the given boundary conditions of a high surface to volume ratio. 

PMID- 25951110
TI  - Rare Earth core/shell nanobarcodes for multiplexed trace biodetection.
AB  - Multiplexed detection technology has been attractive for its simultaneous assay
      of several analytes, which play significant roles in applications such as
      screening for combinatorial chemistry, genetic analysis, and clinical
      diagnostics. This work reports a novel and potentially powerful encoding system
      based upon dispersible suspension arrays of multilayer rare earth core/shell
      nanoparticles that are capable of multiplexed, high-sensitivity reporting for
      biomolecule detection by the Z-contrast imaging. These nanobarcode arrays are
      encoded by nanostructure design based on different atomic numbers. With the well
      resolved high-angle annular dark-field scanning transmission electron microscopy
      (HAADF-STEM) decoding technique, many thousands of unique nanobarcodes can be
      identified by multilayer core/shell nanostructure. Their applications to
      multiplexed biodetection of DNA demonstrated the highly sensitive (picomole)
      features of this novel nanobarcode system. 

PMID- 25951109
TI  - The role of interleukin-10 and hyaluronan in murine fetal fibroblast function in
      vitro: implications for recapitulating fetal regenerative wound healing.
AB  - BACKGROUND: Mid-gestation fetal cutaneous wounds heal scarlessly and this has
      been attributed in part to abundant hyaluronan (HA) in the extracellular matrix
      (ECM) and a unique fibroblast phenotype. We recently reported a novel role for
      interleukin 10 (IL-10) as a regulator of HA synthesis in the fetal ECM, as well
      as the ability of the fetal fibroblast to produce an HA-rich pericellular matrix
      (PCM). We hypothesized that IL-10-mediated HA synthesis was essential to the
      fetal fibroblast functional phenotype and, moreover, that this phenotype could be
      recapitulated in adult fibroblasts via supplementation with IL-10 via an HA
      dependent process. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the differences in
      functional profile, we compared metabolism (MTS assay), apoptosis (caspase-3
      staining), migration (scratch wound assay) and invasion (transwell assay) between
      C57Bl/6J murine fetal (E14.5) and adult (8 weeks) fibroblasts. We found that
      fetal fibroblasts have lower rates of metabolism and apoptosis, and an increased
      ability to migrate and invade compared to adult fibroblasts, and that these
      effects were dependent on IL-10 and HA synthase activity. Further, addition of IL
      10 to adult fibroblasts resulted in increased fibroblast migration and invasion
      and recapitulated the fetal phenotype in an HA-dependent manner.
      CONCLUSIONS/SIGNIFICANCE: Our data demonstrates the functional differences
      between fetal and adult fibroblasts, and that IL-10 mediated HA synthesis is
      essential for the fetal fibroblasts' enhanced invasion and migration properties.
      Moreover, IL-10 via an HA-dependent mechanism can recapitulate this aspect of the
      fetal phenotype in adult fibroblasts, suggesting a novel mechanism of IL-10 in
      regenerative wound healing.

PMID- 25951111
TI  - Antagonism of Acute Sulfide Poisoning in Mice by Nitrite Anion without
      Methemoglobinemia.
AB  - There are currently no FDA-approved antidotes for H2S/sulfide intoxication.
      Sodium nitrite, if given prophylactically to Swiss Webster mice, was shown to be
      highly protective against the acute toxic effects of sodium hydrosulfide (~LD40
      dose) with both agents administered by intraperitoneal injections. However,
      sodium nitrite administered after the toxicant dose did not detectably ameliorate
      sulfide toxicity in this fast-delivery, single-shot experimental paradigm.
      Nitrite anion was shown to rapidly produce NO in the bloodstream, as judged by
      the appearance of EPR signals attributable to nitrosylhemoglobin and
      methemoglobin, together amounting to less than 5% of the total hemoglobin
      present. Sulfide-intoxicated mice were neither helped by the supplemental
      administration of 100% oxygen nor were there any detrimental effects. Compared to
      cyanide-intoxicated mice, animals surviving sulfide intoxication exhibited very
      short knockdown times (if any) and full recovery was extremely fast (~15 min)
      irrespective of whether sodium nitrite was administered. Behavioral experiments
      testing the ability of mice to maintain balance on a rotating cylinder showed no
      motor impairment up to 24 h post sulfide exposure. It is argued that antagonism
      of sulfide inhibition of cytochrome c oxidase by NO is the crucial antidotal
      activity of nitrite rather than formation of methemoglobin. 

PMID- 25951112
TI  - [EurSafety Health-Net: MRSA Eradication in Nursing Homes and Home Care - A
      Practice Report].
AB  - In 2009 the project EurSafety Health-Net, funded by Interreg IVa, was initiated
      in order to create a cross-border quality alliance to enhance patient safety in
      the field of infectious diseases. Within this framework, several studies and
      projects addressing key topics of infection control were carried out. We describe
      the two-year project "MRSA decolonisation in care settings (MSP)", which aimed at
      evaluating a simple and economic way of decolonisation of non-hospitalised MRSA
      carriers in 2 districts in Lower Saxony. In the course of the project 181
      decolonisations of MRSA carriers were performed by nursing homes and nursing
      services for outpatients in cooperation with the local public health authorities
      of the districts Ammerland and Grafschaft Bentheim. Of 181 cases 134 were
      eligible for statistical analysis. The project provided protocols for 2 different
      starting situations: 1) Continuing and completing a decolonisation treatment
      subsequent to a hospital stay by nursing services for outpatients or in a nursing
      home. 2) Starting a decolonisation treatment in a nursing home or by nursing
      services for outpatients. The carriers were provided with the required materials
      either by the hospitals (situation 1) or by the local public health authorities
      (situation 2) free of charge. The decolonisation treatment and the testing were
      offered only to carriers free of properties deemed as decolonisation obstacles
      and was applied without involvement of the general practitioner. Short- and long
      term success of the 5 day decolonisation treatment was tested afterwards by two
      swabs (14 days and 6 months after the end of the treatment). The results of the 6
      month control swabs showed that 45% of the carriers were successfully decolonised
      in the long term. All parties involved regarded the procedure of the MSP project
      as effective with respect to the target. Thus, even after the project was
      finished, both districts continued applying the MSP protocol. 

PMID- 25951113
TI  - ["As Good as it Gets at Home" - Reasons for Institutionalisation in Dementia].
AB  - AIM: What are the reasons for institutionalising community-dwelling persons with
      dementia? METHOD: A written survey of family caregivers and general practitioners
      was undertaken. RESULTS: Within 2 years 47 of 351 people with dementia (13%) were
      institutionalised. The person with dementia was involved in the decision in only
      1/3 of the cases. The 3 most common reasons were: ensuring the best possible
      care, high expenditure of care-giving time at home, deterioration of the health
      of the care-receiver. CONCLUSIONS: From the ethical point of view the exclusion
      of the persons with dementia from the decision-making with regard to
      institutionalisation has to be examined critically. The often given reason of
      ensuring the best possible care through institutionalisation could be
      counteracted by the improvement of community-based care.

PMID- 25951114
TI  - [Patient Participation in Development of Quality Indicators using the Example of
      National Disease Management Guidelines for Chronic Heart Failure - A Qualitative
      Analysis of Collective Perspectives].
AB  - PURPOSE: In this qualitative study it was investigated by group discussions with
      patients suffering from chronic heart failure, how relevant the existing quality
      indicators of the National Disease Management Guidelines for Chronic Heart
      Failure are being estimated. METHODS: 6 group discussions were performed. The
      sample was formed from 4 mixed-gender groups, a male group and a female group.
      Participants were recruited from local heart sports groups. For the
      interpretation a method similar to the grounded theory was used. RESULTS: The
      main conclusion is that in principle quality indicators are accepted. However,
      many of these indicators neglect the everyday aspects of patients' life.
      Participants show a disposition of "yes - but" regarding the quality indicators.
      This phenomenon could be theoretically grasped using the concept of order of
      knowledge. While participants keep referring to an order of everyday knowledge,
      quality indicators make recourse to a medical order of knowledge. Both orders of
      knowledge may compete with each other. CONCLUSIONS: The professional knowledge
      order of medicine needs to open up to a patients' knowledge order. Patient
      representatives in health care bodies need to be trained to develop a reflexive
      point of view to different knowledge orders enabling them to represent patients'
      everyday knowledge more confidently. Otherwise there is danger of conformation to
      the professional knowledge order of medicine only for reasons of being recognised
      as equal partners.

PMID- 25951115
TI  - [What are the Prerequisites for a Successful Cooperation between Nursing Homes
      and Physicians? - Results of a Mixed-methods Cross-Sectional Study in Bavarian
      Nursing Homes].
AB  - Aim: This mixed-methods cross-sectional study examined the cooperation between
      nursing home staff and physicians in Bavarian nursing homes in order to
      understand which organisational and communication measures are resulting in
      satisfying teamwork among professional groups in nursing homes. Methods: In 3
      interview rounds nursing home staff, general practitioners, medical specialists,
      dentists, nursing home residents, and relatives in 52 nursing homes were
      interviewed using a questionnaire that was enhanced after every round.
      Additionally, focus group interviews have been performed in 2 nursing homes.
      Results: 443 persons involved in patient care, 50 residents and 47 relatives
      participated in the structured interviews. 22 persons attended the focus group
      interviews. 65% of the nursing homes required regular visits of general
      practitioners and 36% or, respectively, 27% required regular or on demand visits
      of specialists. 47% of the nursing home staff that was asked about this issue
      stated that it would make their work easier if only a small number of physicians
      were in charge of their institution. Measures for improvement of medical care in
      nursing homes most frequently suggested by interview partners responsible for
      patient care were: better communication (9%), better remuneration of physicians'
      nursing home visits (7%, nurses and physicians) and less bureaucracy and regular
      physicians' visits (5% in each question). Conclusion: Because of the composition
      of our study sample it cannot be assumed that the results are representative for
      all Bavarian nursing homes. Confidence in one another, low number of persons in
      charge, binding agreements and regular physicians' nursing home visits are
      essential for a successful cooperation between providing physicians and nursing
      home staff.

PMID- 25951116
TI  - [Do Learning Effects Lead to Path Dependencies in Hospitals? Study of the Effects
      on Reorganisation Processes].
AB  - Based on the observations concerning the economic situation, a fundamental
      restructuring of hospital organisations is repeatedly called for in the
      literature. Strengthening the process orientation by "raising" the grade of
      efficiency is frequently argued as an organisational measure. This work
      theoretically investigates where the obstacles to organisational change in
      hospitals can lie using the path dependency theory. Specifically, socio
      professional influences on the learning behaviour of hospital staff will be
      discussed. Influences that affect inter-professional cooperation in hospitals are
      identified.

PMID- 25951117
TI  - [Can Quality of Patient Identification be Influenced by Training? - Results of a
      Randomised Multicentre Study with Multimodal Intervention].
AB  - Background: Attributing clinical care to patients unambiguously is a precondition
      for patient safety. The German Coalition for Patient Safety has published a
      recommendation on this topic. Issue: The here presented study examined whether
      and to what extent documentation quality as one determining factor of correct
      patient identification can be improved positively by inter-professional training.
      Method: In our randomised multi-centric study physicians and nurses from 8 units
      in 4 hospitals were trained. The control group consisted of untrained unit teams.
      Effects of the intervention were measured by investigating documentation errors
      in clinical records before and after the training. Results: As a result of our
      intervention the number of documents with documentation errors/patient charts
      could be reduced by 37.3% (p<0.001). Conclusion: The results of the study point
      to the training of recommendations on preventing errors as an effective
      instrument for the improvement of patient safety.

PMID- 25951118
TI  - [Robustness of Hospital Benchmarking with the Hospital Standardized Mortality
      Ratio (HSMR): An Analysis of Secondary Data from 37 German Hospitals].
AB  - Introduction: Internationally, the hospital standardized mortality ratio is
      increasingly used as a risk-adjusted simple measure for quality control. Goodness
      of fit of different risk models in Germany and robustness of hospital comparisons
      were evaluated with a secondary data analysis. Methods: Anonymized routine data
      from the year 2012 of 37 hospitals of the association Quality Indicators for
      Ecclesiastical Hospitals were used. 2 independent risk models and the observed
      mortality were compared, the risk models considered both the original and the
      adapted forms. Results: The risk models showed an area under curve between 0.906
      [95% CI 0.904-0.908] and 0.920 [0.918-0.922]. There was a significant correlation
      between the risk models and the observed mortality with a correlation coefficient
      between 0.388 (p<0.05) and 0.936 (p<0.01). 26 hospitals had an identical
      assessment in all risk models comparing their HSMR with the group. 2 hospitals
      achieved a positive and a negative assessment taking into account the observed
      mortality. Conclusion: The quality of the risk models is high and the hospital
      comparison with the HSMR remained stable. However, it is unclear whether the
      differences are caused by quality-related issues or by different structures and
      case-mix. Therefore, the HSMR is primarily intended for quality management
      purposes within German hospitals.

PMID- 25951119
TI  - [Poliomyelitis--Challenges for the Last Mile of the Eradication Programme].
AB  - The World Health Organisation initiated the Global Polio Eradication Initiative
      in the year 1988. With the large-scale application of routine and mass
      vaccinations in children under the age of 5 years, polio disease has become
      restricted to only 3 endemic countries (Afghanistan, Pakistan and Nigeria) by
      today. However, since the beginning of the 21st century, increasing numbers of
      secondary polio epidemics have been observed which were triggered through
      migration, political turmoil and weak health systems. In addition, there emerged
      serious technical (e. g., back-mutations of oral vaccine virus to wild virus) and
      socio-political (refusal of vaccinations in Muslim populations of Nigeria and
      Pakistan) problems with the vaccination in the remaining endemic countries. It
      thus appears questionable if the current eradiation initiative will reach its
      goal in the foreseeable future. 

PMID- 25951121
TI  - Use of a Secondary Essay in the Residency Application Process.

PMID- 25951120
TI  - An Exclusion Zone for Ca2+ Channels around Docked Vesicles Explains Release
      Control by Multiple Channels at a CNS Synapse.
AB  - The spatial arrangement of Ca2+ channels and vesicles remains unknown for most
      CNS synapses, despite of the crucial importance of this geometrical parameter for
      the Ca2+ control of transmitter release. At a large model synapse, the calyx of
      Held, transmitter release is controlled by several Ca2+ channels in a "domain
      overlap" mode, at least in young animals. To study the geometrical constraints of
      Ca2+ channel placement in domain overlap control of release, we used stochastic
      MCell modelling, at active zones for which the position of docked vesicles was
      derived from electron microscopy (EM). We found that random placement of Ca2+
      channels was unable to produce high slope values between release and presynaptic
      Ca2+ entry, a hallmark of domain overlap, and yielded excessively large release
      probabilities. The simple assumption that Ca2+ channels can be located anywhere
      at active zones, except below a critical distance of ~ 30 nm away from docked
      vesicles ("exclusion zone"), rescued high slope values and low release
      probabilities. Alternatively, high slope values can also be obtained by placing
      all Ca2+ channels into a single supercluster, which however results in
      significantly higher heterogeneity of release probabilities. We also show
      experimentally that high slope values, and the sensitivity to the slow Ca2+
      chelator EGTA-AM, are maintained with developmental maturation of the calyx
      synapse. Taken together, domain overlap control of release represents a highly
      organized active zone architecture in which Ca2+ channels must obey a certain
      distance to docked vesicles. Furthermore, domain overlap can be employed by near
      mature, fast-releasing synapses. 

PMID- 25951122
TI  - Optimizing atrial fibrillation management: from ICU and beyond.
AB  - Atrial fibrillation (AF) that newly occurs during critical illness presents
      challenges for both short- and long-term management. During critical illness,
      patients with new-onset AF are clinically evaluated for hemodynamic instability
      owing to the arrhythmia as well as for potentially reversible arrhythmia
      triggers. Hemodynamically significant AF that persists during critical illness
      may be treated with heart rate or rhythm control strategies. Recent evidence
      suggests that patients in whom AF develops during acute illness (eg, sepsis,
      postoperatively) have high long-term risks for AF recurrence and for AF
      associated complications, such as stroke, heart failure, and death. Therefore, we
      suggest increased efforts to improve communication of AF events between inpatient
      and outpatient providers and to reassess patients who had experienced new-onset
      AF during critical illness after they transition to the post-ICU setting. We
      describe various strategies for the assessment and long-term management of
      patients with new-onset AF during critical illness. 

PMID- 25951123
TI  - Sinonasal extramedullary plasmacytoma: a population-based incidence and survival
      analysis.
AB  - BACKGROUND: Sinonasal extramedullary plasmacytoma (SN-EMP) is a rare plasma cell
      neoplasm. Published literature on this tumor largely consists of case reports and
      case-series with small sample sizes. This study analyzed population-based data on
      SN-EMP patients to understand demographic and clinical features as well as
      incidence and survival trends. METHODS: The Surveillance, Epidemiology, and End
      Results (SEER) database was queried for SN-EMP and other head and neck EMP (HN
      EMP) cases from 1973 to 2011. Cases were analyzed to determine patient
      demographics, initial treatment modality, and survival outcomes. RESULTS: Of 778
      patients identified with EMP in the head and neck region, 367 patients had SN-EMP
      and 411 had other HN-EMP. There was a strong male predilection found, with a male
      to-female ratio of 3.65:1 in the SN-EMP group and 1.87:1 in the other HN-EMP
      group. The majority of the patients presented with localized disease in both SN
      EMP (84.4%) and other HN-EMP (81.0%) groups. The most common treatment modality
      reported in this database was surgery with adjuvant radiotherapy in both SN-EMP
      (46.3%) and other HN-EMP (38.9%) groups, followed by radiotherapy alone (SN-EMP:
      40.7%; other HN-EMP: 34.2%). Five-year and 10-year disease-specific survival
      rates were comparable between SN-EMP (88.2% and 83.3%, respectively) and other HN
      EMP (90.0% and 87.4%, respectively) (p = 0.6016 and p = 0.4015, respectively).
      CONCLUSION: This study analyzed the largest cohort of SN-EMP patients to date.
      There was no statistically significant survival advantage found for any 1
      particular treatment modality over other treatment modalities in both SN-EMP and
      other HN-EMP.

PMID- 25951124
TI  - Adaptive sampling in two-phase designs: a biomarker study for progression in
      arthritis.
AB  - Response-dependent two-phase designs are used increasingly often in
      epidemiological studies to ensure sampling strategies offer good statistical
      efficiency while working within resource constraints. Optimal response-dependent
      two-phase designs are difficult to implement, however, as they require
      specification of unknown parameters. We propose adaptive two-phase designs that
      exploit information from an internal pilot study to approximate the optimal
      sampling scheme for an analysis based on mean score estimating equations. The
      frequency properties of estimators arising from this design are assessed through
      simulation, and they are shown to be similar to those from optimal designs. The
      design procedure is then illustrated through application to a motivating
      biomarker study in an ongoing rheumatology research program.

PMID- 25951125
TI  - Charge Dynamics in Solution-Processed Nanocrystalline CuInS2 Solar Cells.
AB  - We investigate charge dynamics in solar cells constructed using solution
      processed layers of CuInS2 (CIS) nanocrystals (NCs) as the electron donor and CdS
      as the electron acceptor. By using time-resolved spectroscopic techniques, we are
      able to observe photoinduced absorptions that we attribute to the mobile hole
      carriers in the NC film. In combination with transient photocurrent and
      photovoltage measurements, we monitor charge dynamics on time scales from 300 fs
      to 1 ms. Carrier dynamics are investigated for devices with CIS layers composed
      of either colloidally synthesized 1,3-benzenedithiol-capped nanocrystals or in
      situ sol-gel synthesized thin films as the active layer. We find that deep
      trapping of holes in the colloidal NC cells is responsible for decreases in the
      open-circuit voltage and fill factor as compared to those of the sol-gel
      synthesized CIS/CdS cell. 

PMID- 25951126
TI  - Iron and FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR-dependent
      regulation of proteins and genes in Arabidopsis thaliana roots.
AB  - Iron is an essential micronutrient for plants, and iron deficiency requires a
      variety of physiological adaptations. FIT (FER-LIKE IRON DEFICIENCY-INDUCED
      TRANSCRIPTION FACTOR) is essential for the regulation of iron uptake in
      Arabidopsis thaliana roots. FIT is transcriptionally as well as
      posttranscriptionally regulated in response to iron supply. To investigate to
      which extent posttranscriptional regulation upon iron deficiency applies to
      proteins and to determine the dependency on FIT, we performed a parallel
      proteomic and transcriptomic study with wild-type, a fit knock-out mutant, and a
      FIT overexpressing Arabidopsis line. Among 92 proteins differentially regulated
      by iron and/or FIT, we identified 30 proteins, which displayed differential
      regulation at the transcriptional level. Eleven protein spots were regulated in
      at least one of the data points even contrary to the respective genes dependent
      on FIT. We found ten proteins in at least two forms. The analysis of functional
      classification showed enriched GO terms among the posttranscriptionally regulated
      genes and of proteins, that were downregulated or absent in the fit knock-out
      mutant. Taken together, we provide evidence for iron and FIT-dependent
      posttranscriptional regulation in iron homeostasis in A. thaliana. 

PMID- 25951127
TI  - A Titan exits stage left: Summary of the Waun Ki Hong Festschrift.

PMID- 25951128
TI  - Anticancer Effect of Ursodeoxycholic Acid in Human Oral Squamous Carcinoma HSC-3
      Cells through the Caspases.
AB  - Bear bile was used as a traditional medicine or tonic in East Asia, and
      ursodeoxycholic acid (UDCA) is the most important compound in bear bile. Further,
      synthetic UDCA is also used in modern medicine and nutrition; therefore, its
      further functional effects warrant research, in vitro methods could be used for
      the fundamental research of its anticancer effects. In this study, the apoptotic
      effects of UDCA in human oral squamous carcinoma HSC-3 cells through the
      activation of caspases were observed by the experimental methods of MTT (3-(4,5
      dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay, DAPI (4',6
      diamidino-2-phenylindole) staining, flow cytometry analysis, RT-PCR (reverse
      transcription-polymerase chain reaction) assay and Western blot assay after HSC-3
      cells were treated by different concentrations of UDCA. With 0 to 400 MUg/mL UDCA
      treatment, UDCA had strong growth inhibitory effects in HSC-3 cells, but had
      almost no effect in HOK normal oral cells. At concentrations of 100, 200 and 400
      MUg/mL, UDCA could induce apoptosis compared to untreated control HSC-3 cells.
      Treatment of 400 MUg/mL UDCA could induce more apoptotic cancer cells than 100
      and 200 MUg/mL treatment; the sub-G1 DNA content of 400 MUg/mL UDCA treated
      cancer cells was 41.3% versus 10.6% (100 MUg/mL) and 22.4% (200 MUg/mL). After
      different concentrations of UDCA treatment, the mRNA and protein expressions of
      caspase-3, caspase-8, caspase-9, Bax, Fas/FasL (Fas ligand), TRAIL (TNF-related
      apoptosis-inducing ligand), DR4 (death receptor 4) and DR5 (death receptor 5)
      were increased in HSC-3 cells, and mRNA and protein expressions of Bcl-2 (B-cell
      lymphoma 2), Bcl-xL (B-cell lymphoma-extra large), XIAP (X-linked inhibitor of
      apoptosis protein), cIAP-1 (cellular inhibitor of apoptosis 1), cIAP-2 (cellular
      inhibitor of apoptosis 2) and survival were decreased. Meanwhile, at the highest
      concentration of 400 MUg/mL, caspase-3, caspase-8, caspase-9, Bax, Fas/FasL,
      TRAIL, DR4, DR5, and IkappaB-alpha expression levels were the highest, and Bcl-2,
      Bcl-xL, XIAP, cIAP-1, cIAP-2, survival, and NF-kappaB expression levels were the
      lowest. These results proved that UDCA could induce apoptosis of HSC-3 cancer
      cells through caspase activation, and the higher concentration of UDCA had
      stronger effects in vitro. UDCA might be a good nutrient for oral cancer
      prevention. 

PMID- 25951130
TI  - An explanation of the pathophysiology of adverse neurodevelopmental outcomes in
      iron deficiency.
AB  - Iron deficiency (ID) is a major public health problem worldwide among children
      aged 0-12 months. Several factors seem to contribute to the iron-deficient state
      in infancy, including insufficient antenatal and neonatal iron supplementation,
      exclusive breastfeeding, and early umbilical cord clamping after birth. The most
      concerning complications of ID, except for anemia, are related to altered long
      term neurodevelopment. Clinical studies have shown a negative impact of ID anemia
      on fetal and neonatal behavior including impairments of motor maturity, autonomic
      response, memory/learning, and mood. ID-induced defects during infancy seem to
      persist later in life, even after ID treatment. The underlying mechanisms involve
      dysfunctional myelination, neurotransmission alterations, and altered
      synaptogenesis and/or dendritogenesis. The purpose of the present review is to
      summarize these mechanisms and to provide recommendations for future clinical
      research in the field. 

PMID- 25951129
TI  - Can skin exposure to sunlight prevent liver inflammation?
AB  - Liver inflammation contributes towards the pathology of non-alcoholic fatty liver
      disease (NAFLD). Here we discuss how skin exposure to sunlight may suppress liver
      inflammation and the severity of NAFLD. Following exposure to sunlight-derived
      ultraviolet radiation (UVR), the skin releases anti-inflammatory mediators such
      as vitamin D and nitric oxide. Animal modeling studies suggest that exposure to
      UVR can prevent the development of NAFLD. Association studies also support a
      negative link between circulating 25-hydroxyvitamin D and NAFLD incidence or
      severity. Clinical trials are in their infancy and are yet to demonstrate a clear
      beneficial effect of vitamin D supplementation. There are a number of potentially
      interdependent mechanisms whereby vitamin D could dampen liver inflammation, by
      inhibiting hepatocyte apoptosis and liver fibrosis, modulating the gut microbiome
      and through altered production and transport of bile acids. While there has been
      a focus on vitamin D, other mediators induced by sun exposure, such as nitric
      oxide may also play important roles in curtailing liver inflammation. 

PMID- 25951131
TI  - Identification and evaluation of potentially inappropriate medications (PIMs) in
      hospitalized geriatric patients using Beers criteria.
AB  - BACKGROUND: The aim of the study was to identify and evaluate potentially
      inappropriate medication (PIM) in geriatric patients using Beers criteria and
      also to identify adverse drug events (ADEs) due to PIMs and various drug-drug
      interactions. METHODS: The medications in the prescriptions of patients above 60
      years of age, their dosage regimen respective of their diagnosis were analyzed.
      Each medication was then checked with Beers list tables, and any medication if
      mentioned in the Beers list, was noted along with its strength of recommendation
      and quality of evidence. Any adverse drug event (ADE) due to PIM was identified.
      Causality of the events was assessed by Naranjo's Scale. The number of drug-drug
      interactions per prescription and the severity of each interaction were also
      analyzed. The collected data from 200 subjects were subjected to statistical
      treatments using Statistical Package for Social Sciences (SPSS) software version
      16.0 for WINDOWS. RESULTS: Based on the Beers criteria 2012, 106 out of 200 (53%)
      prescriptions had at least one PIM prescribed. A sum of 1690 medications was
      prescribed as a whole for the entire study subjects. Among which, 134 PIMs were
      identified. Most commonly prescribed PIMs were benzodiazepines (39, 19.5%),
      followed by sliding scale use of insulin (31, 15.5%), and prazosin at a rate of
      11.5% (23). A total of 10 ADEs were identified during the study. The average
      number of drug interactions observed among total samples was found to be 3.0+/
      6.0 with 0+/-5.0 serious interactions, 2+/-4.0 significant interactions requiring
      close monitoring, and 0+/-6.0 minor interactions. CONCLUSIONS: The study shows
      high prevalence of prescribing PIMs in hospitalized elderly patients; PIM also
      caused incidence of ADEs; and serious drug-drug interactions were scarce among
      the patients.

PMID- 25951132
TI  - The risk of macrovascular complications in subjects genotyped for common IL-6
      gene and TNF-alpha gene variants.

PMID- 25951133
TI  - Progression from light chain myeloma to secondary plasma cell leukemia
      accompanied by peripheral blood eosinophilia.

PMID- 25951134
TI  - The experience of nursing students who make mistakes in clinical.
AB  - The experience of nursing students who make mistakes during clinical practice is
      poorly understood. The literature identifies clinical practice mistakes as a
      significant issue in nursing practice and education but there is very little
      research on the topic. This study used a grounded theory approach to explore the
      experience of undergraduate nursing students who had made at least one mistake in
      their clinical practice. What emerged is a theory that illuminates the process of
      how students move through the positive and negative elements of the mistake
      experience the core variable that emerged from the study was "living through the
      mistake experience." The mistake experience was clearly a traumatic process for
      nursing students and students reported feeling unprepared and lacking the
      capability to manage the mistake experience. A number of recommendations for
      nursing education are proposed. 

PMID- 25951135
TI  - Effect of anesthesia on renal R2 * measured by blood oxygen level-dependent MRI.
AB  - Blood oxygen level-dependent (BOLD) MRI is increasingly being used to assess
      renal tissue oxygenation during disease based on the transverse relaxation rate
      (R2 *). In preclinical small animal models, the requisite use of anesthesia
      during imaging may lead to functional changes which influence R2 * and confound
      results. The purpose of this study was to evaluate the effects of four common
      anesthetic compounds on renal R2 * in healthy mice. Five female ICR mice were
      imaged with BOLD MRI approximately 25 min after induction with isoflurane (Iso;
      1% or 1.5%, delivered in 100% O2 ), ketamine/xylazine (KX), sodium pentobarbital
      (PB) or 2,2,2-tribromoethanol (TBE). A significant effect of anesthetic agent on
      R2 * was observed in all tissue layers of the kidney, including the cortex, outer
      stripe of the outer medulla (OSOM), inner stripe of the outer medulla (ISOM) and
      inner medulla (IM). Pairwise significant differences in R2 * between specific
      agents were found in the cortex, OSOM and ISOM, with the largest difference
      observed in the ISOM between 1.5% Iso (26.6 +/- 1.7 s(-1) ) and KX (66.0 +/- 7.1
      s(-1) ). The difference between 1% Iso and KX in the ISOM was not abolished when
      KX was administered with supplemental 100% O2 or when 1% Iso was delivered in 21%
      O2 , indicating that the fraction of inspired oxygen did not account for the
      observed differences. Our results indicate that the choice of anesthesia has a
      large influence on the observed R2 * in mouse kidney, and anesthetic effects must
      be considered in the design and interpretation of renal BOLD MRI studies.

PMID- 25951136
TI  - Nutrient retention and fate of iron-binding phenolic compounds during the injera
      processing of tannin-free and high-tannin sorghum.
AB  - BACKGROUND: Traits such as bird-, insect- and mould-resistance are the focus in
      selecting improved sorghum varieties, but this often increases the tannin
      content, which can negatively affect iron bioavailability. The grain
      characteristics, nutrient retention, and the fate of iron-binding polyphenols
      (IBPs) during injera processing, an Ethiopian traditional fermented pancake, were
      investigated using agriculturally improved tannin-free (TFC) and high-tannin
      (HTC) sorghum cultivars. RESULTS: The HTC had significantly higher IBP contents
      than the TFC (P < 0.05). Decortication led to iron (24-27%), calcium (18-43%),
      IBP (catechol 35-41%, galloyl 35-42%), and tannin (12-35%) losses. Sourdough
      fermentation reduced the IBP and tannin concentrations in HTC, but had no effect
      on the IBP concentrations in TFC. The modified injera processing that included
      pre-soaking resulted in the highest IBP reductions (galloyl 73% and catechol
      71%). CONCLUSION: Nutrient retention in HTC and TFC processing was different.
      Including a pre-soaking step during injera processing of HTC could counter the
      negative effects of IBP on iron absorption, while benefiting from the agronomic
      features of HTC.

PMID- 25951137
TI  - Multi-service highly sensitive rectifier for enhanced RF energy scavenging.
AB  - Due to the growing implications of energy costs and carbon footprints, the need
      to adopt inexpensive, green energy harvesting strategies are of paramount
      importance for the long-term conservation of the environment and the global
      economy. To address this, the feasibility of harvesting low power density ambient
      RF energy simultaneously from multiple sources is examined. A high efficiency
      multi-resonant rectifier is proposed, which operates at two frequency bands (478
      496 and 852-869 MHz) and exhibits favorable impedance matching over a broad input
      power range (-40 to -10 dBm). Simulation and experimental results of input
      reflection coefficient and rectified output power are in excellent agreement,
      demonstrating the usefulness of this innovative low-power rectification
      technique. Measurement results indicate an effective efficiency of 54.3%, and an
      output DC voltage of 772.8 mV is achieved for a multi-tone input power of -10
      dBm. Furthermore, the measured output DC power from harvesting RF energy from
      multiple services concurrently exhibits a 3.14 and 7.24 fold increase over single
      frequency rectification at 490 and 860 MHz respectively. Therefore, the proposed
      multi-service highly sensitive rectifier is a promising technique for providing a
      sustainable energy source for low power applications in urban environments. 

PMID- 25951138
TI  - Beauty matters: social preferences in a three-person ultimatum game.
AB  - Preference for beauty is human nature, as previous behavior studies have
      supported the notion of "beauty premium" in which attractive people were more
      easily to get promoted and receive higher salaries. In the present study, 29
      males were recruited to participate in a three-person ultimatum game (UG)
      including a proposer, a responder and a powerless third player. Each subject,
      playing as the responder, had to decide whether to accept an offer from the
      allocator both for himself and a female third person. We aimed to elucidate how
      the facial attractiveness of the female subject affected the male subjects'
      fairness and decision-making in social exchanges. Frontal feedback-related
      negativity (FRN) in response to four offers in an attractive-face condition
      revealed no significant differences between offers; however, when the companion
      was an unattractive female, an "unfair/fair" offer, which assigned a lower share
      to the responder and a fair share to the third player, elicited the largest FRN.
      Furthermore, when the third player was offered the smallest amount ("fair/unfair"
      offer), a larger FRN was generated in an attractive-face condition than
      unattractive-face condition. In the "unfair/fair" offer condition in which
      subjects received a smaller allocation than the third person, the beauty of their
      female counterparts attenuated subjects' aversion to inequality, resulting in a
      less negative FRN in the frontal region and an increased acceptance ratio.
      However, the influence of the third player's facial attractiveness only affected
      the early evaluation stage: late P300 was found to be immune to the "beauty
      premium". Under the two face conditions, P300 was smallest following an
      "unfair/fair" offer, whereas the amplitudes in the other three offer conditions
      exhibited no significant differences. In addition, the differentiated neural
      features of processing facial attractiveness were also determined and indexed by
      four event-related potentials (ERP) components: N170, frontal N1, N2 and late
      positive potentials (LPPs). 

PMID- 25951139
TI  - Discovery of Novel Liver-Stage Antimalarials through Quantum Similarity.
AB  - Without quantum theory any understanding of molecular interactions is incomplete.
      In principal, chemistry, and even biology, can be fully derived from non
      relativistic quantum mechanics. In practice, conventional quantum chemical
      calculations are computationally too intensive and time consuming to be useful
      for drug discovery on more than a limited basis. A previously described,
      original, quantum-based computational process for drug discovery and design
      bridges this gap between theory and practice, and allows the application of
      quantum methods to large-scale in silico identification of active compounds.
      Here, we show the results of this quantum-similarity approach applied to the
      discovery of novel liver-stage antimalarials. Testing of only five of the model
      predicted compounds in vitro and in vivo hepatic stage drug inhibition assays
      with P. berghei identified four novel chemical structures representing three
      separate quantum classes of liver-stage antimalarials. All four compounds
      inhibited liver-stage Plasmodium as a single oral dose in the quantitative PCR
      mouse liver-stage sporozoites-challenge model. One of the newly identified
      compounds, cethromycin [ABT-773], a macrolide-quinoline hybrid, is a drug with an
      extensive (over 5,000 people) safety profile warranting its exploitation as a new
      weapon for the current effort of malaria eradication. The results of our
      molecular modeling exceed current state-of-the-art computational methods. Drug
      discovery through quantum similarity is data-driven, agnostic to any particular
      target or disease process that can evaluate multiple phenotypic, target-specific,
      or co-crystal structural data. This allows the incorporation of additional
      pharmacological requirements, as well as rapid exploration of novel chemical
      spaces for therapeutic applications. 

PMID- 25951142
TI  - The Stabilizing Effects in Gold Carbene Complexes.
AB  - Bonding and stabilizing effects in gold carbene complexes are investigated by
      using Kohn-Sham density functional theory (DFT) and the intrinsic bond orbital
      (IBO) approach. The pi-stabilizing effects of organic substituents at the carbene
      carbon atom coordinated to the gold atom are evaluated for a series of recently
      isolated and characterized complexes, as well as intermediates of prototypical
      1,6-enyne cyclization reactions. The results indicate that these effects are of
      particular importance for gold complexes especially because of the low pi
      backbonding contribution from the gold atom. 

PMID- 25951141
TI  - A Variable Sampling Interval Synthetic Xbar Chart for the Process Mean.
AB  - The usual practice of using a control chart to monitor a process is to take
      samples from the process with fixed sampling interval (FSI). In this paper, a
      synthetic X control chart with the variable sampling interval (VSI) feature is
      proposed for monitoring changes in the process mean. The VSI synthetic X chart
      integrates the VSI X chart and the VSI conforming run length (CRL) chart. The
      proposed VSI synthetic X chart is evaluated using the average time to signal
      (ATS) criterion. The optimal charting parameters of the proposed chart are
      obtained by minimizing the out-of-control ATS for a desired shift. Comparisons
      between the VSI synthetic X chart and the existing X, synthetic X, VSI X and EWMA
      X charts, in terms of ATS, are made. The ATS results show that the VSI synthetic
      X chart outperforms the other X type charts for detecting moderate and large
      shifts. An illustrative example is also presented to explain the application of
      the VSI synthetic X chart.

PMID- 25951140
TI  - Analysis of mutations in 7 genes associated with neuronal excitability and
      synaptic transmission in a cohort of children with non-syndromic infantile
      epileptic encephalopathy.
AB  - Epileptic Encephalopathy (EE) is a heterogeneous condition in which cognitive,
      sensory and/or motor functions deteriorate as a consequence of epileptic
      activity, which consists of frequent seizures and/or major interictal paroxysmal
      activity. There are various causes of EE and they may occur at any age in early
      childhood. Genetic mutations have been identified to contribute to an increasing
      number of children with early onset EE which had been previously considered as
      cryptogenic. We identified 26 patients with Infantile Epileptic Encephalopathy
      (IEE) of unknown etiology despite extensive workup and without any specific
      epilepsy syndromic phenotypes. We performed genetic analysis on a panel of 7
      genes (ARX, CDKL5, KCNQ2, PCDH19, SCN1A, SCN2A, STXBP1) and identified 10 point
      mutations [ARX (1), CDKL5 (3), KCNQ2 (2), PCDH19 (1), SCN1A (1), STXBP1 (2)] as
      well as one microdeletion involving both SCN1A and SCN2A. The high rate (42%) of
      mutations suggested that genetic testing of this IEE panel of genes is
      recommended for cryptogenic IEE with no etiology identified. These 7 genes are
      associated with channelopathies or synaptic transmission and we recommend early
      genetic testing if possible to guide the treatment strategy. 

PMID- 25951143
TI  - Generalized quantum interference of correlated photon pairs.
AB  - Superposition and indistinguishablility between probability amplitudes have
      played an essential role in observing quantum interference effects of correlated
      photons. The Hong-Ou-Mandel interference and interferences of the path-entangled
      photon number state are of special interest in the field of quantum information
      technologies. However, a fully generalized two-photon quantum interferometric
      scheme accounting for the Hong-Ou-Mandel scheme and path-entangled photon number
      states has not yet been proposed. Here we report the experimental demonstrations
      of the generalized two-photon interferometry with both the interferometric
      properties of the Hong-Ou-Mandel effect and the fully unfolded version of the
      path-entangled photon number state using photon-pair sources, which are
      independently generated by spontaneous parametric down-conversion. Our
      experimental scheme explains two-photon interference fringes revealing single-
      and two-photon coherence properties in a single interferometer setup. Using the
      proposed interferometric measurement, it is possible to directly estimate the
      joint spectral intensity of a photon pair source. 

PMID- 25951144
TI  - The oral food desensitization in the Italian allergy centres.
AB  - BACKGROUND: Attempts aimed at inducing food tolerance through oral food
      desensitization (OFD) for the treatment of IgE-mediated food allergies are
      increasing. In Italy, a number of allergy centres offer this procedure.
      OBJECTIVE: To collect information on how these centres are organized, how
      patients are selected, the methods used to administer OFD and how adverse
      reactions are managed. METHODS: A questionnaire was e-mailed to all the Italian
      allergy centres offering OFD. RESULTS: The survey shows a high degree of
      variability between centres. A correct diagnosis of food allergy is crucial for
      selecting patients for OFD. In the Italian allergy centres, oral food challenges
      are mostly open label (84%), but in 16% of cases they are single-blind (8%) or
      double-blind (8%). A high proportion of allergy centres (83%) offer OFD to
      children presenting forms of anaphylaxis triggered by traces--or very low doses-
      of food allergen. The majority of allergy centres (76%) enroll patients over 3
      years of age, with 44% enrolling patients above the age of 5. Not-controlled
      asthma, unreliability of parents in the management of OFD and/or risk of adverse
      events, are the main reasons for exclusion from the procedure. CONCLUSION:
      Although OFD may sometimes be successful and may be considered a valid
      alternative to an elimination diet, further randomized controlled trials are
      needed, in order to clarify some controversial points, such as the
      characteristics of the child undergoing OFD, and the methods of food preparation
      and administration. Moreover, further studies should further investigate OFD
      safety, efficacy and costs.

PMID- 25951146
TI  - Anaphylaxis: a one-year survey on Medical Emergency Service in Liguria (Italy).
AB  - Anaphylaxis is a severe, life-threatening, generalized or systemic
      hypersensitivity reaction. The diagnosis is mainly based on clinical ground. This
      study aimed at evaluating the records of phone calls and medical visits for
      anaphylaxis occurred in Region Liguria during 2013. The phone call is managed in
      each headquarter, and classified according to a level of care intensity and a
      presumed level of criticality, according to established criteria. Criticality is
      then re-evaluated (detected criticality) at the end of medical visit, following
      the same score adding the black code defining died patients. Most of the phone
      calls (553) to the MES were recorded in summer (37.4%). Anaphylaxis was confirmed
      in about half of patients. There was a fair agreement between presumed and
      detected criticality (k=0.322, p<0.001). In addition, 530 patients (95.8%) were
      transported to Emergency Room. In conclusion, the present study shows that
      anaphylaxis represents a serious and relevant medical problem in the general
      population at any age, and should always be carefully managed.

PMID- 25951145
TI  - Proposal of a skin tests based approach for the prevention of recurrent
      hypersensitivity reactions to iodinated contrast media.
AB  - The purpose of the present work is to evaluate the efficacy of an approach that
      combines clinical history, skin tests results, and premedication, in preventing
      recurrent hypersensitivity reactions to iodinated contrast media (ICM). Skin
      Prick tests, Intradermal tests, and Patch tests were performed in 36 patients
      with a previous reaction to ICM. All patients underwent a second contrast
      enhanced radiological procedure with an alternative ICM selected on the basis of
      the proposed approach. After alternative ICM re-injection, only one patient
      presented a mild NIR. The proposed algorithm, validated in clinical settings
      where repeated radiological exams are needed, offers a safe and practical
      approach for protecting patients from recurrent hypersensitivity reactions to
      ICM. 

PMID- 25951147
TI  - Overcoming recurrent spontaneous abortions in women suffering from IgG subclass
      deficiency: high efficiency of low dose intravenous immunoglobulins treatment.
AB  - PROBLEM: It's well known that iv. immunoglobulins may be useful to overcome
      habitual abortions, but the mechanisms at the base of a successful outcome and
      the likelihoods are still unknown. METHOD OF STUDY: In one hundred and sixty
      women with habitual abortions and one hundred and sixty healthy mothers, we
      evaluated blood IgG subclasses; among the patients, sixteen merely showed IgG
      subclass deficiency, after leaving out any autoimmunity and/or coagulation
      disorders. All the patients (100%) showed IgG3, twelve (75%) IgG1, eight (50%)
      IgG4 and six (37,5%) IgG2 deficiency; healthy control people's IgG subclasses
      fell in normal range in 156 women, but just four women showed IgG2 and IgG4
      deficiency with neither immune deficiency's clinical marks nor increased
      vulnerability to infections. All the patients were treated with whole
      immunoglobulins iv. infusion (200 mg/kg/monthly) all over the pregnancy. RESULTS:
      The successful pregnancy rate is very high (>90%): 100% out of women showing IgG1
      (12/12), 87,5% of IgG3 (14/16), 75% of IgG4 (6/8) and 66% of IgG2 deficiency
      (4/6) had successful pregnancies. The Odd's Ratio between IgG subclass deficiency
      and recurrent abortions is 4,33 with confidence interval of 95%; chi square value
      is 7.68 (p<0.025). CONCLUSIONS: Low dose immunoglobulin infusion is the only
      effective way to reach successful pregnancy, despite previous habitual abortions
      in patients suffering from IgG subclass deficiency without autoimmunity and/or
      coagulation disorders, likely restoring idiotype-antiidiotype network; showing
      evidence of IgG subclasses deficiency (mostly IgG1 and IgG3) may help identify
      patients who can benefit from iv. immunoglobulin treatment.

PMID- 25951148
TI  - Severe bronchiectasis in a patient with common variable immunodeficiency.
AB  - BACKGROUND: Bronchiectasis are common in Common Variable Immunodeficiency. These
      patients are prone to infection, leading to progressive lung destruction and
      accelerated FEV1 decline. CLINICAL CASE: 40 year-old man, with recurrent
      respiratory infections, autoimmunity and diarrhea since age 7. At 17 CVID was
      diagnosed and IVIgG was started. During the following years, respiratory symptoms
      progressively worsened and bronchiectasis was found on thoracic computed
      tomography. Bronchoscopy revealed Pseudomonas aeruginosa in bronchoalveolar
      lavage and bronchial secretions cultures. Eradication therapy led to clinical
      improvement. DISCUSSION: This case report stresses the importance of regular
      microbiological screening and appropriate antibiotherapy. Early/aggressive
      treatment may significantly impact on patients' evolution.

PMID- 25951149
TI  - Immediate-type hypersensitivity reaction to Mannitol as drug excipient (E421): a
      case report.
AB  - Allergic reactions to mannitol have been reported rarely, despite its widespread
      use as a drug and as a food excipient. This is the first case report in which
      oral mannitol induces an immediate type hypersensitivity as a drug excipient, in
      a 42 year old man affected by rhinitis to olive tree pollen. Unusual and
      undervalued risk factors for mannitol hypersensitivity are examined. 

PMID- 25951152
TI  - The ASCCP, 2000 and Beyond.

PMID- 25951150
TI  - Allergic contact dermatitis in child with odontoiatric face-mask.

PMID- 25951153
TI  - Interrater Variability in Diagnosis of Cervical Biopsies from Women with HIV-1:
      Results from the Women's Interagency HIV Study.
AB  - OBJECTIVES: To determine interrater variability in classifying cervical biopsies
      from women with human immunodeficiency virus (HIV). MATERIALS AND METHODS:
      Cervical biopsies performed on women participating in the Women's Interagency HIV
      Study (WIHS) were read at the six participating sites. A 10% random sample was
      retrieved and reviewed using standardized terminology by pathologists with a
      special interest in gynecologic pathology. Results were compared with kappa
      values and Mantel-Haentzel tests. RESULTS: Biopsies from 288 HIV-seropositive and
      24 HIV-seronegative women were reviewed. The weighted kappa value of 0.67
      indicated moderate to strong agreement between original and review diagnoses,
      with a range of 0.54 to 0.84 across sites. No cancers were identified.
      Significantly more specimens showing cervical intraepithelial neoplasia (CIN)
      grade 2 or 3 were identified by review pathologists (p = .02). CIN2 or CIN3 was
      graded less severely by local pathologists in 18 (51%) of 35 cases, all from HIV
      seropositive women. Local pathologists' diagnoses of CIN2 or CIN3 were downgraded
      by reviewers in 4 of 21 cases (19%). Discrepancies were more common among women
      with lower CD4 lymphocyte counts. CONCLUSIONS: Although discrepancies occur,
      interrater correlation in the interpretation of cervical biopsies from women with
      HIV is moderate to strong.

PMID- 25951154
TI  - Diagnostic value of the papanicolaou smear in lower genital tract infections
      during pregnancy.
AB  - OBJECTIVES: To evaluate the diagnostic value of the Pap smear in lower genital
      tract infections during pregnancy. MATERIALS AND METHODS: A total of 190 pregnant
      women were examined in the Lower Genital Tract and Colposcopy clinics of the
      Obstetrics Division at the University Hospital de Clinicas "Jose de San Martin"
      of University of Buenos Aires from April to August 1997. Samples were taken from
      the vaginal fornix for microbiologic study and from the exocervix for Pap smear.
      Both the sensitivity and specificity test of the Pap smear for diagnosing lower
      genital tract infections were calculated considering the microbiologic study as
      the reference standard. RESULTS: The sensitivity of the Pap smear for Candida
      spp., bacterial vaginosis and Trichomonas vaginalis compared with microbiologic
      study was 50, 81, and 78, respectively. The specificity for the same study was
      96%, 93%, and 100%, respectively. CONCLUSIONS: Pap smear for diagnosing lower
      genital tract infections is useful when positive results are found for these
      infections because of its high specificity.

PMID- 25951155
TI  - Vulvar vestibulitis: response to hypocontactant vulvar therapy.
AB  - OBJECTIVES: To determine clinical response of women with vulvar vestibulitis
      syndrome (VVS) to a hypocontactant vulvar skin regimen. MATERIALS AND METHODS: A
      clinical trial was conducted with 85 patients who met Friedrich's criteria for
      VVS. Pretreatment average duration of vulvar pain was 24 months. Of the 53
      sexually active patients, 62% had Level II to III and 38% had Level I
      dyspareunia. All patients were treated with a hypocontactant vulvar skin regimen
      for a minimum of four months. Follow-up ranged 6 to 36 months. Follow-up clinical
      visits and questionnaires were used to determine the clinical effects. RESULTS:
      Six months following initiation of therapy, the response rate for reduction in
      vulvar pain was 77%-20% complete response, 57% partial response-and 23% no
      response. Additionally, 60% reported greater than or equal to one level of
      dyspareunia improvement. CONCLUSIONS: Contact irritants may be a factor causing
      vestibular pain in VVS patients.

PMID- 25951156
TI  - Morphometric Characterization of HPV-Related Lesions of Uterine Cervix.
AB  - OBJECTIVES: This study addresses three issues related to human papillomavirus
      (HPV) cervical lesions: identification of HPV in histologic normal tissue,
      identification of HPV subtypes with risk for cervical cancer, and histologic
      differences between HPV not associated to cervical intraepithelial neoplasia
      (CIN1) lesions (condyloma) and HPV associated to CIN1 lesions. MATERIALS AND
      METHODS: The authors histologically classified 48 cervical biopsy slides into
      three groups: normal (n = 22), condyloma (n = 20), and CIN1 (n = 6). Morphometric
      analyses of nuclear and cytoplasmic ratio for area, length, and diameter of 25
      cells per case were performed. Histologic reports and in situ hybridization for
      HPV subtype were compared to morphometric data to assess correlation among them.
      RESULTS: Using image analysis, the authors correctly classified all cases except
      two into histologic or in situ hybridization diagnosis. Morphometry helped
      identify viral changes in cells that appeared histologically normal, HPV subtype
      at risk in condyloma lesions, and condyloma from those combining HPV lesions and
      CIN1. CONCLUSIONS: There were enough data supporting morphometric distinction of
      HPV-related cervical lesions assessed by nuclear and cytoplasmic ratio.

PMID- 25951157
TI  - Presentation and screening history of indigent women with cervical cancer:
      implications for prevention.
AB  - OBJECTIVE: To identify missed opportunities for screening and early diagnosis of
      indigent patients with cervical cancer. MATERIALS AND METHODS: The authors
      conducted a retrospective review of charts and databases for demographic
      information, presenting symptoms, staging data, prior health system contacts, and
      Papanicolaou smears. Women with cervical cancer were evaluated at an urban public
      hospital between July 1, 1994, and March 31, 1998. RESULTS: Among 177 women with
      cervical cancer where record could be retrieved, 82 were in stage I, 49 were in
      II, 25 were in III, and 11 were in IV. Symptoms attributable to cancer were
      present in 153 (86%) cases, but asymptomatic women were more likely to have stage
      I cancers (21 of 23 versus 70 of 153, p < .0005). Only 54 (31%) women had prior
      visits recorded, with emergency services the most common site for visits. Only 23
      (43%) of these had prior cytology recorded, four of which were false negatives.
      Stage I cancers were found in 18 (78%) of these women, compared to 13 (42%) of
      the 31 women previously seen without a recorded Papanicolaou smear (p < .02).
      Women with prior visits to gynecology services or clinics were more likely to
      have Papanicolaou smears recorded (10 of 13 versus 9 of 32 at other sites, p <
      .0005) but not more likely to have stage I cancer (10 of 13 versus 20 of 41, p =
      .08). CONCLUSIONS: Further reductions in cervical cancer rates are likely to
      require outreach, screening in nontraditional sites, and refinement of public
      sector screening programs.

PMID- 25951158
TI  - Speculoscopy for Triage of Patients with an Abnormal Pap Smear: Data from the
      GISPE Study.
AB  - OBJECTIVE: This study evaluates the performance of Papanicolaou smear combined
      with speculoscopy in improving the predictive value of minor grade cervical
      cytological abnormalities. MATERIALS AND METHODS: A total of 3,300 asymptomatic
      women who had routine cervical smears were studied in 32 Italian centers. All
      these women underwent Pap smear and speculoscopy. The women positive at Pap smear
      or speculoscopy (n = 908) were referred for colposcopy and directed punch
      biopsy/endocervical curettage was performed when appropriate. RESULTS: Of the 908
      patients referred for colposcopy, 538 underwent biopsy; 92 of these had a
      cervical lesion (cervical intraepithelial neoplasia [CIN]) confirmed on histology
      (67 CIN1 and 25 CIN2-3). Speculoscopy pointed out an area to biopsy in 84% of the
      CIN1 and in 75% of the CIN2-3 cases among women who showed minor (low-grade
      squamous intraepithelial lesion or less) cytological abnormalities. CONCLUSIONS:
      The potential combination of cytology and speculoscopy as an intermediate test in
      patients with minor grade cytologic (atypical squamous cells of undetermined
      significance or low-grade squamous intraepithelial lesion) cervical changes may
      decrease the number of recalls and directed biopsies in a cost-effective manner.

PMID- 25951159
TI  - Management of Abnormal Pap Smears (MAPS): Implications of Terminology Used in
      Cytopathology.

PMID- 25951160
TI  - Hysteroscopic resection of uterine lipoleiomyoma: case study and literature
      review.
AB  - ? ABSTRACT: : A case of a uterine lipoleiomyoma within an endometrial polyp is
      presented. Lipoleiomyomas represent a rare, benign gynecological entity that can
      present as post-menopausal bleeding or pelvic mass. Hysteroscopic appearance, MRI
      images, and histological images of the polyp are included. The English literature
      pertaining to the radiological appearance and cytological origins of
      lipoleiomyoma is reviewed.

PMID- 25951161
TI  - Home study course: autumn 2000.
AB  - ? OBJECTIVE: : The Home Study Course is intended for the practicing colposcopist
      or practitioner who is seeking to develop or enhance his or her colposcopic
      skills. The goal of the course is to present colposcopic cases that are unusual
      or instructive in terms of appearance, presentation, or management, or that
      demonstrate new and important knowledge in the area of colposcopy or pathology.
      Participants may benefit from reading and studying the material or from testing
      their knowledge by answering the questions. ? ACCME ACCREDITATION: : The American
      Society for Colposcopy and Cervical Pathology (ASCCP) is accredited by the
      Accreditation Council for Continuing Medical Education (ACCME) to sponsor
      continuing medical education for physicians. The ASCCP designates this continuing
      medical education activity for 1 credit hour in Category I of the Physician's
      Recognition Award of the American Medical Association. Credit is available for
      those who choose to apply. The Home Study Course is planned and produced in
      accordance with the ACCME's Essential Areas and Elements.

PMID- 25951162
TI  - The american society for colposcopy and cervical pathology: hagerstown, MD.

PMID- 25951164
TI  - Author's Manuscript Checklist.

PMID- 25951163
TI  - Clinical question: ask the experts.

PMID- 25951165
TI  - L-Carnitine Supplementation Reduces Short-Term Neutrophil-Lymphocyte Ratio in
      Patients Undergoing Coronary Artery Bypass Grafting.
AB  - This study aims to investigate whether preoperative L-carnitine supplementation
      affects the neutrophil-to-lymphocyte ratio (NLR) in patients undergoing coronary
      artery bypass grafting surgery. The neutrophil-to-lymphocyte ratio is an
      inflammatory marker that has proven usefulness for predicting postoperative
      complications in coronary artery bypass surgery. A lot of studies concerning the
      role of L-carnitine in the immune system have been performed, contradictory
      results have been reported on its effects on absolute numbers of WBC subtypes.
      This randomized, double-blinded, placebo-controlled study was conducted among
      patients scheduled for coronary artery bypass grafting surgery between June 2012
      and December 2013 in our cardiovascular surgery clinic. A total of 60 consecutive
      patients were randomized and divided into 2 groups. The first group received 2 g
      of L-carnitine in 1000 mL of 0.9% saline solution infused over 24 hours for each
      of the 3 preoperative days (L-carnitine group, n = 30), or only 1000 mL of 0.9%
      saline solution for the same time period (placebo group, n = 30). The basal
      values of leukocyte, neutrophil, lymphocyte counts, and neutrophil to lymphocyte
      ratio were similar in the 2 groups. After L-carnitine supplementation (just
      before surgery), leukocyte and neutrophil counts of the L-carnitine group were
      significantly lower than those of the placebo group (7.7 +/- 1.5 versus 9.7 +/-
      2.6, P < 0.001 and 4.6 +/- 1.3 versus 6.5 +/- 2.2, P < 0.001). On postoperative
      day 1, lymphocyte counts were significantly higher in the L-carnitine group (1.1
      +/- 0.6 versus 0.8 +/- 0.9, P < 0.001). Moreover, the increase in NLR was
      significantly lower in the L-carnitine group at postoperative day 1 (20.7 +/-
      13.8 versus 10.8 +/- 4.1, P < 0.001). Preoperative L-carnitine supplementation
      may reduce neutrophil-lymphocyte ratio during the early postoperative period of
      coronary artery bypass grafting surgery. 

PMID- 25951166
TI  - Promotion of Viral IRES-Mediated Translation Initiation under Mild Hypothermia.
AB  - Internal ribosome entry site (IRES)-mediated translation is an essential
      replication step for certain viruses. As IRES-mediated translation is regulated
      differently from cap-dependent translation under various cellular conditions, we
      sought to investigate whether temperature influences efficiency of viral IRES
      mediated translation initiation by using bicistronic reporter constructs
      containing an IRES element of encephalomyocarditis virus (EMCV), foot-and-mouth
      disease virus (FMDV), hepatitis C virus (HCV), human rhinovirus (HRV) or
      poliovirus (PV). Under mild hypothermic conditions (30 and 35 degrees C), we
      observed increases in the efficiency of translation initiation by HCV and HRV
      IRES elements compared to translation initiation at 37 degrees C. The promotion
      of HRV IRES activity was observed as early as 2 hours after exposure to mild
      hypothermia. We also confirmed the promotion of translation initiation by HRV
      IRES under mild hypothermia in multiple cell lines. The expression levels and
      locations of polypyrimidine tract-binding protein (PTB) and upstream of N-Ras
      (unr), the IRES trans-acting factors (ITAFs) of HCV and HRV IRES elements, were
      not modulated by the temperature shift from 37 degrees C to 30 degrees C. Taken
      together, this study demonstrates that efficiency of translation initiation by
      some viral IRES elements is temperature dependent. 

PMID- 25951167
TI  - Activity of Antibiotics against Mycobacterium Species Commonly Found in
      Laboratory Zebrafish.
AB  - The Zebrafish Danio rerio is a popular vertebrate model organism used in a wide
      range of research fields. Importance is placed on Zebrafish health and the
      maintenance of disease-free laboratory fish so that experimental studies are not
      inadvertently affected. Mycobacteriosis, a common infection of laboratory
      Zebrafish, is caused by several Mycobacterium species. Little is known regarding
      the potential of antibiotic treatment for Zebrafish mycobacteriosis; however,
      treatment of infected Zebrafish may be appropriate to maintain valuable strains.
      Here, we investigated, in vitro, the antibiotic susceptibility of both rapid- and
      slow-growing isolates of Mycobacterium species from laboratory Zebrafish.
      Antibiotic testing was carried out using a commercially available 96-well
      microtiter plate format. Results indicated that some but not all antibiotics
      tested were effective at inhibiting mycobacterial growth and that susceptibility
      varied among species and strains. Tigecycline, tobramycin, clarithromycin, and
      amikacin were most effective at broad inhibition of rapid-growing mycobacteria;
      whereas, amikacin, clarithromycin, and rifampin were effective at inhibiting all
      slow-growing M. marinum strains tested. Results support the potential for
      targeted antibiotic treatment of Zebrafish infected with mycobacteria, but
      additional testing should be carried out in vivo.

PMID- 25951168
TI  - The elusive role of the prion protein and the mechanism of toxicity in prion
      disease.

PMID- 25951170
TI  - Negativation of Trypanosoma cruzi PCR within Six Months after Treatment of a
      Child with Nifurtimox.

PMID- 25951169
TI  - New mutation in the mouse Xpd/Ercc2 gene leads to recessive cataracts.
AB  - Cataracts are the major eye disorder and have been associated mainly with
      mutations in lens-specific genes, but cataracts are also frequently associated
      with complex syndromes. In a large-scale high-throughput ENU mutagenesis screen
      we analyzed the offspring of paternally treated C3HeB/FeJ mice for obvious
      dysmorphologies. We identified a mutant suffering from rough coat and small eyes
      only in homozygotes; homozygous females turned out to be sterile. The mutation
      was mapped to chromosome 7 between the markers 116J6.1 and D7Mit294;4 other
      markers within this interval did not show any recombination among 160 F2-mutants.
      The critical interval (8.6 Mb) contains 3 candidate genes (Apoe, Six5, Opa3);
      none of them showed a mutation. Using exome sequencing, we identified a c.2209T>C
      mutation in the Xpd/Ercc2 gene leading to a Ser737Pro exchange. During embryonic
      development, the mutant eyes did not show major changes. Postnatal histological
      analyses demonstrated small cortical vacuoles; later, cortical cataracts
      developed. Since XPD/ERCC2 is involved in DNA repair, we checked also for the
      presence of the repair-associated histone gammaH2AX in the lens. During the time,
      when primary lens fiber cell nuclei are degraded, gammaH2AX was strongly
      expressed in the cell nuclei; later, it demarcates clearly the border of the lens
      cortex to the organelle-free zone. Moreover, we analyzed also whether seemingly
      healthy heterozygotes might be less efficient in repair of DNA damage induced by
      ionizing radiation than wild types. Peripheral lymphocytes irradiated by 1Gy
      Cs137 showed 6 hrs after irradiation significantly more gammaH2AX foci in
      heterozygotes than in wild types. These findings demonstrate the importance of
      XPD/ERCC2 not only for lens fiber cell differentiation, but also for the
      sensitivity to ionizing radiation. Based upon these data, we hypothesize that
      variations in the human XPD/ERCC2 gene might increase the susceptibility for
      several disorders besides Xeroderma pigmentosum in heterozygotes under particular
      environmental conditions. 

PMID- 25951171
TI  - Community-Engaged Strategies to Promote Relevance of Research Capacity-Building
      Efforts Targeting Community Organizations.
AB  - OBJECTIVE: The study goal is to highlight strategies for promoting relevance of
      research capacity-building efforts targeting community organizations (CO)s.
      METHODS: Two community partners, representing two COs, were invited to
      participate in CO research development trainings, Community Research Forums
      (Forum)s. Their contributions were documented via Forum document review. Forum
      participants, representatives from other COs, completed post-Forum surveys to
      identify additional training needs and rate Forum impact relative to their
      training expectations. A content-based analysis and descriptive statistics were
      used to summarize needs assessment- and impact-related survey responses,
      respectively. RESULTS: Community partners were involved in eight Forum-related
      activities including marketing (planning), facilitation (implementation), and
      manuscript coauthorship (dissemination). Eighty-one individuals, representing 55
      COs, attended the Forums. Needs assessment responses revealed a desire for
      additional assistance with existing Forum topics (e.g., defining research
      priorities) and a need for new ones (e.g., promoting organizational buy in for
      research). Ninety-one percent of participants agreed that the Forum demonstrated
      the value of research to COs and how to create a research agenda. CONCLUSIONS:
      Including community partners in all Forum phases ensured that CO perspectives
      were integrated throughout. Post-Forum needs and impact assessment results will
      help in tailoring, where needed, future training topics and strategies,
      respectively.

PMID- 25951172
TI  - In the Early Stages of Diabetes, Rat Retinal Mitochondria Undergo Mild Uncoupling
      due to UCP2 Activity.
AB  - In order to maintain high transmembrane ionic gradients, retinal tissues require
      a large amount of energy probably provided by a high rate of both, glycolysis and
      oxidative phosphorylation. However, little information exists on retinal
      mitochondrial efficiency. We analyzed the retinal mitochondrial activity in ex
      vivo retinas and in isolated mitochondria from normal rat retina and from short
      term streptozotocin-diabetic rats. In normal ex vivo retinas, increasing glucose
      concentrations from 5.6 mM to 30 mM caused a four-fold increase in glucose
      accumulation and CO2 production. Retina from diabetic rats accumulated similar
      amounts of glucose. However, CO2 production was not as high. Isolated
      mitochondria from normal rat retina exhibited a resting rate of oxygen
      consumption of 14.6 +/- 1.1 natgO (min.mg prot)(-1) and a respiratory control of
      4.0. Mitochondria from 7, 20 and 45 days diabetic rats increased the resting rate
      of oxygen consumption and the activity of the electron transport complexes; under
      these conditions the mitochondrial transmembrane potential decreased. In spite of
      this, the ATP synthesis was not modified. GDP, an UCP2 inhibitor, increased
      mitochondrial membrane potential and superoxide production in controls and at 45
      days of diabetes. The role of UCP2 is discussed. The results suggest that at the
      early stage of diabetes we studied, retinal mitochondria undergo adaptations
      leading to maintain energetic requirements and prevent oxidative stress.

PMID- 25951173
TI  - Effect of Larval Competition on Extrinsic Incubation Period and Vectorial
      Capacity of Aedes albopictus for Dengue Virus.
AB  - Despite the growing awareness that larval competition can influence adult
      mosquito life history traits including susceptibility to pathogens, the net
      effect of larval competition on human risk of exposure to mosquito-borne
      pathogens remains poorly understood. We examined how intraspecific larval
      competition affects dengue-2 virus (DENV-2) extrinsic incubation period and
      vectorial capacity of its natural vector Aedes albopictus. Adult Ae. albopictus
      from low and high-larval density conditions were orally challenged with DENV-2
      and then assayed for virus infection and dissemination rates following a 6, 9, or
      12-day incubation period using real-time quantitative reverse transcription PCR.
      We then modeled the effect of larval competition on vectorial capacity using
      parameter estimates obtained from peer-reviewed field and laboratory studies.
      Larval competition resulted in significantly longer development times, lower
      emergence rates, and smaller adults, but did not significantly affect the
      extrinsic incubation period of DENV-2 in Ae. albopictus. Our vectorial capacity
      models suggest that the effect of larval competition on adult mosquito longevity
      likely has a greater influence on vectorial capacity relative to any competition
      induced changes in vector competence. Furthermore, we found that large increases
      in the viral dissemination rate may be necessary to compensate for small
      competition-induced reductions in daily survivorship. Our results indicate that
      mosquito populations that experience stress from larval competition are likely to
      have a reduced vectorial capacity, even when susceptibility to pathogens is
      enhanced. 

PMID- 25951174
TI  - Optically anisotropic substrates via wrinkle-assisted convective assembly of gold
      nanorods on macroscopic areas.
AB  - We demonstrate the large-scale organisation of anisotropic nanoparticles into
      linear assemblies displaying optical anisotropy on macroscopic areas.
      Monodisperse gold nanorods with a hydrophilic protein shell are arranged by dip
      coating on wrinkled surfaces and subsequently transferred to indium tin oxide
      (ITO) substrates by capillary transfer printing. We elucidate how tuning the
      wrinkle amplitude enables us to precisely adjust the assembly morphology and
      fabricate single, double and triple nanorod lines. For the single lines, we
      quantify the order parameter of the assemblies as well as interparticle distances
      from scanning electron microscopy (SEM) images. We find an order parameter of
      0.97 and a mean interparticle gap size of 7 nm. This combination of close to
      perfect uni-axial alignment and close-packing gives rise to pronounced
      macroscopic anisotropic optical properties due to strong plasmonic coupling. We
      characterise the optical response of the assemblies on ITO-coated glass via
      UV/vis/NIR spectroscopy and determine an optical order parameter of 0.91. The
      assemblies are thus plasmonic metamaterials, as their periodicity and building
      block sizes are well below the optical wavelength. The presented approach does
      not rely on lithographic patterning and provides access to functional materials,
      which could have applications in subwavelength waveguiding, photovoltaics, and
      for large-area metamaterial fabrication. 

PMID- 25951175
TI  - The Breast Cancer-Associated Glycoforms of MUC1, MUC1-Tn and sialyl-Tn, Are
      Expressed in COSMC Wild-Type Cells and Bind the C-Type Lectin MGL.
AB  - Aberrant glycosylation occurs in the majority of human cancers and changes in
      mucin-type O-glycosylation are key events that play a role in the induction of
      invasion and metastases. These changes generate novel cancer-specific glyco
      antigens that can interact with cells of the immune system through carbohydrate
      binding lectins. Two glyco-epitopes that are found expressed by many carcinomas
      are Tn (GalNAc-Ser/Thr) and STn (NeuAcalpha2,6GalNAc-Ser/Thr). These glycans can
      be carried on many mucin-type glycoproteins including MUC1. We show that the
      majority of breast cancers carry Tn within the same cell and in close proximity
      to extended glycan T (Galbeta1,3GalNAc) the addition of Gal to the GalNAc being
      catalysed by the T synthase. The presence of active T synthase suggests that loss
      of the private chaperone for T synthase, COSMC, does not explain the expression
      of Tn and STn in breast cancer cells. We show that MUC1 carrying both Tn or STn
      can bind to the C-type lectin MGL and using atomic force microscopy show that
      they bind to MGL with a similar dead adhesion force. Tumour associated STn is
      associated with poor prognosis and resistance to chemotherapy in breast
      carcinomas, inhibition of DC maturation, DC apoptosis and inhibition of NK
      activity. As engagement of MGL in the absence of TLR triggering may lead to
      anergy, the binding of MUC1-STn to MGL may be in part responsible for some of the
      characteristics of STn expressing tumours.

PMID- 25951177
TI  - Oral methylphenidate for the treatment of refractory facial dystonias.
AB  - Oral methylphenidate (Ritalin, Novartis) has been reported to alleviate symptoms
      of benign essential blepharospasm in an off-label application. This series
      presents 3 patients with refractory periorbital and facial dystonias, including
      blepharospasm, apraxia of eyelid opening, and oromandibular dystonia unresponsive
      to standard treatments who experienced a response to oral methylphenidate
      therapy. While the mechanisms for facial dystonias have not been elucidated,
      there is evidence to suggest that they are on the spectrum with Parkinson
      disease. Given the role of dopamine loss in the pathogenesis of Parkinson, the
      authors' speculate that methylphenidate may be acting on the pathway directly
      involved in facial dystonias. To the authors' knowledge, this is the first report
      of a case of successful treatment of blepharospasm refractory to upper eyelid
      myectomy with methylphenidate monotherapy. 

PMID- 25951176
TI  - Natural Variation Identifies ICARUS1, a Universal Gene Required for Cell
      Proliferation and Growth at High Temperatures in Arabidopsis thaliana.
AB  - Plants are highly sensitive to environmental changes and even small variations in
      ambient temperature have severe consequences on their growth and development.
      Temperature affects multiple aspects of plant development, but the processes and
      mechanisms underlying thermo-sensitive growth responses are mostly unknown. Here
      we exploit natural variation in Arabidopsis thaliana to identify and characterize
      novel components and processes mediating thermo-sensitive growth responses in
      plants. Phenotypic screening of wild accessions identified several strains
      displaying pleiotropic growth defects, at cellular and organism levels,
      specifically at high ambient temperatures. Positional cloning and
      characterization of the underlying gene revealed that ICARUS1 (ICA1), which
      encodes a protein of the tRNAHis guanylyl transferase (Thg1) superfamily, is
      required for plant growth at high temperatures. Transcriptome and gene marker
      analyses together with DNA content measurements show that ICA1 loss-of-function
      results in down regulation of cell cycle associated genes at high temperatures,
      which is linked with a block in G2/M transition and endoreduplication. In
      addition, plants with mutations in ICA1 show enhanced sensitivity to DNA damage.
      Characterization of additional strains that carry lesions in ICA1, but display
      normal growth, shows that alternative splicing is likely to alleviate the
      deleterious effects of some natural mutations. Furthermore, analyses of worldwide
      and regional collections of natural accessions indicate that ICA1 loss-of
      function has arisen several times independently, and that these occur at high
      frequency in some local populations. Overall our results suggest that ICA1
      mediated-modulation of fundamental processes such as tRNAHis maturation, modify
      plant growth responses to temperature changes in a quantitative and reversible
      manner, in natural populations. 

PMID- 25951178
TI  - Local application of ibandronate/gelatin sponge improves osteotomy healing in
      rabbits.
AB  - Delayed healing or non-union of skeletal fractures are common clinical
      complications. Ibandronate is a highly potent anti-catabolic reagent used for
      treatment of osteopenia and fracture prevention. We hypothesized that local
      application of ibandronate after fracture fixation may improve and sustain callus
      formation and therefore prevent delayed healing or non-union. This study tested
      the effect of local application of an ibandronate/gelatin sponge composite on
      osteotomy healing. A right-side distal-femoral osteotomy was created surgically,
      with fixation using a k-wire, in forty adult male rabbits. The animals were
      divided into four groups of ten animals and treated by: (i) intravenous injection
      of normal saline (Control); (ii) local implantation of absorbable gelatin sponge
      (GS); (iii) local implantation of absorbable GS containing ibandronate (IB+GS),
      and (iv) intravenous injection of ibandronate (IB i.v.). At two and four weeks
      the affected femora were harvested for X-ray photography, computed tomography
      (CT), biomechanical testing and histopathology. At both time-points the results
      showed that the calluses in both the ibandronate-treated groups, but especially
      in the IB+GS group, were significantly larger than in the control and GS groups.
      At four weeks the cross sectional area (CSA) and mechanical test results of
      ultimate load and energy in the IB+GS group were significantly higher than in
      other groups. Histological procedures showed a significant reduction in
      osteoclast numbers in the IB+GS and IB i.v. groups at day 14. The results
      indicate that local application of an ibandronate/gelatin sponge biomaterial
      improved early osteotomy healing after surgical fixation and suggest that such
      treatment may be a valuable local therapy to enhance fracture repair and
      potentially prevent delayed or non-union. 

PMID- 25951179
TI  - Rab27A Is Present in Mouse Pancreatic Acinar Cells and Is Required for Digestive
      Enzyme Secretion.
AB  - The small G-protein Rab27A has been shown to regulate the intracellular
      trafficking of secretory granules in various cell types. However, the presence,
      subcellular localization and functional impact of Rab27A on digestive enzyme
      secretion by mouse pancreatic acinar cells are poorly understood. Ashen mice,
      which lack the expression of Rab27A due to a spontaneous mutation, were used to
      investigate the function of Rab27A in pancreatic acinar cells. Isolated
      pancreatic acini were prepared from wild-type or ashen mouse pancreas by
      collagenase digestion, and CCK- or carbachol-induced amylase secretion was
      measured. Secretion occurring through the major-regulated secretory pathway,
      which is characterized by zymogen granules secretion, was visualized by Dextran
      Texas Red labeling of exocytotic granules. The minor-regulated secretory pathway,
      which operates through the endosomal/lysosomal pathway, was characterized by
      luminal cell surface labeling of lysosomal associated membrane protein 1 (LAMP1).
      Compared to wild-type, expression of Rab27B was slightly increased in ashen mouse
      acini, while Rab3D and digestive enzymes (amylase, lipase, chymotrypsin and
      elastase) were not affected. Localization of Rab27B, Rab3D and amylase by
      immunofluorescence was similar in both wild-type and ashen acinar cells. The GTP
      bound states of Rab27B and Rab3D in wild-type and ashen mouse acini also remained
      similar in amount. In contrast, acini from ashen mice showed decreased amylase
      release induced by CCK- or carbachol. Rab27A deficiency reduced the apical cell
      surface labeling of LAMP1, but did not affect that of Dextran-Texas Red
      incorporation into the fusion pockets at luminal surface. These results show that
      Rab27A is present in mouse pancreatic acinar cells and mainly regulates secretion
      through the minor-regulated pathway. 

PMID- 25951180
TI  - Inhibitors of the Candida albicans Major Facilitator Superfamily Transporter
      Mdr1p Responsible for Fluconazole Resistance.
AB  - OBJECTIVE: To identify a novel class of inhibitors of fungal transporters
      involved in drug resistance. METHODS: A series of structurally-related low
      molecular mass compounds was synthesized using combinatorial chemistry of a
      cyclobutene-dione (squarile) core. These compounds were screened for their
      inhibition of plasma membrane Major Facilitator Superfamily (MFS) and ATP-binding
      cassette (ABC) transporters responsible for efflux pump-mediated drug resistance
      in the fungal pathogen Candida albicans. Strains of Saccharomyces cerevisiae that
      specifically overexpress the MFS pump CaMdr1p or the ABC transporter CaCdr1p were
      used in primary screens and counterscreens, respectively, and to detect
      inhibition of glucose-dependent Nile Red efflux. Efflux pump inhibition, activity
      as pump substrates and antifungal activity against yeast and clinical isolates
      expressing efflux pumps were determined using agarose diffusion susceptibility
      assays and checkerboard liquid chemosensitization assays with fluconazole.
      RESULTS: The screen identified five structurally-related compounds which
      inhibited CaMdr1p. Two compounds, A and B, specifically chemosensitized AD/CaMDR1
      to FLC in a pH-dependent fashion and acted synergistically with FLC in
      checkerboard liquid MIC assays but compound B had limited solubility. Compound A
      chemosensitized to FLC the azole-resistant C. albicans strain FR2, which over
      expresses CaMdr1p, inhibited Nile Red efflux mediated by CaMdr1p but not CaCdr1p
      and was not toxic to cultured human cells. A minor growth-inhibitory effect of B
      on AD/CaMDR1, but not on AD/CaCDR1 and AD/CaCDR2, indicated that compound B may
      be a substrate of these transporters. The related compound F was found to have
      antifungal activity against the three pump over-expressing strains used in the
      study. CONCLUSIONS: Compound A is a 'first in class' small molecule inhibitor of
      MFS efflux pump CaMdr1p.

PMID- 25951181
TI  - Role of JMJD6 in Breast Tumourigenesis.
AB  - BACKGROUND: Protein arginine methylation is a common post translational
      modification that regulates protein properties. This modification is carried out
      by a family of nine arginine methyltransferases (PRMTs). Arginine methylation has
      already been linked to tumourigenesis as overexpression of these enzymes was
      associated with various cancers, notably in breast cancers. Since the Jumonji
      Domain Containing 6 protein (JMJD6) possesses an arginine demethylase activity
      able to remove the methyl mark, we wanted to assess its potential role in breast
      tumourigenesis. METHODS: The expression of the protein by tissue microarray
      immunohistochemical staining was performed on a cohort of 133 breast tumours.
      Using cell lines stably overexpressing or knocked down for JMJD6, we evaluated
      its role on cell proliferation, cell migration, colony formation and mice tumour
      xenografts. RESULTS: The analysis of JMJD6 expression in a cohort of breast
      tumour samples indicates that JMJD6 was highly expressed in aggressive breast
      tumours. Moreover, high expression of JMJD6 was associated with poor disease-free
      survival of patients in this cohort. JMJD6 silencing in breast tumoural cells
      promotes certain characteristics of tumourigenesis including proliferation,
      migration in vitro, and tumour growth in vivo. These effects are dependent on its
      demethylase activity as an enzymatic dead mutant lost these properties.
      CONCLUSIONS: Although JMJD6 displays anti-tumoral properties in cell lines, its
      expression in breast tumours may be a marker of poor prognosis, suggesting that
      its function could be altered in breast cancer.

PMID- 25951182
TI  - Correction: Two novel mutations in myosin binding protein C slow causing distal
      arthrogryposis type 2 in two large Han Chinese families may suggest important
      functional role of immunoglobulin domain C2.

PMID- 25951183
TI  - Remembering mumps.

PMID- 25951185
TI  - Overexpression of Telomerase Protects Human and Murine Lung Epithelial Cells from
      Fas- and Bleomycin-Induced Apoptosis via FLIP Upregulation.
AB  - High doses of bleomycin administered to patients with lymphomas and other tumors
      lead to significant lung toxicity in general, and to apoptosis of epithelial
      cells, in particular. Apoptosis of alveolar epithelium is an important step in
      the pathogenesis of bleomycin-induced pulmonary fibrosis. The Fas-FasL pathway is
      one of the main apoptotic pathways involved. Telomerase is a ribonucleoprotein
      RNA-dependent DNA polymerase complex consisting of an RNA template and a
      catalytic protein, telomerase reverse transcriptase (TERT). Telomerase also
      possess extra-telomeric roles, including modulation of transcription of anti
      apoptotic genes, differentiation signals, and more. We hypothesized that
      telomerase overexpression affects Fas-induced epithelial cell apoptosis by an
      extra-telomeric role such as regulation of anti-apoptotic genes, specifically
      FLICE-like inhibitory protein (FLIP). Telomerase in mouse (MLE) and human (A549)
      lung epithelial cell lines was upregulated by transient transfection using cDNA
      hTERT expression vector. Telomerase activity was detected using a real-time PCR
      based system. Bleomycin, and bleomycin-induced Fas-mediated apoptosis following
      treatment with anti-Fas activating mAb or control IgG, were assessed by Annexin V
      staining, FACS analysis, and confocal microscopy; caspase cleavage by Western
      blot; FLIP or Fas molecule detection by Western blot and flow cytometry. hTERT
      transfection of lung epithelial cells resulted in a 100% increase in their
      telomerase activity. Fas-induced lung epithelial cell apoptosis was significantly
      reduced in hTERT-transfected cells compared to controls in all experiments. Lung
      epithelial cells with increased telomerase activity had higher levels of FLIP
      expression but membrane Fas expression was unchanged. Upregulation of hTERT+ in
      human lung epithelial cells and subsequent downregulation of FLIP by shFLIP-RNA
      annulled hTERT-mediated resistance to apoptosis. Telomerase-mediated FLIP
      overexpression may be a novel mechanism to confer protection from apoptosis in
      bleomycin-exposed human lung epithelial cells. 

PMID- 25951184
TI  - Contrasting Transmission Dynamics of Co-endemic Plasmodium vivax and P.
      falciparum: Implications for Malaria Control and Elimination.
AB  - BACKGROUND: Outside of Africa, P. falciparum and P. vivax usually coexist. In
      such co-endemic regions, successful malaria control programs have a greater
      impact on reducing falciparum malaria, resulting in P. vivax becoming the
      predominant species of infection. Adding to the challenges of elimination, the
      dormant liver stage complicates efforts to monitor the impact of ongoing
      interventions against P. vivax. We investigated molecular approaches to inform
      the respective transmission dynamics of P. falciparum and P. vivax and how these
      could help to prioritize public health interventions. METHODOLOGY/PRINCIPAL
      FINDINGS: Genotype data generated at 8 and 9 microsatellite loci were analysed in
      168 P. falciparum and 166 P. vivax isolates, respectively, from four co-endemic
      sites in Indonesia (Bangka, Kalimantan, Sumba and West Timor). Measures of
      diversity, linkage disequilibrium (LD) and population structure were used to
      gauge the transmission dynamics of each species in each setting. Marked
      differences were observed in the diversity and population structure of P. vivax
      versus P. falciparum. In Bangka, Kalimantan and Timor, P. falciparum diversity
      was low, and LD patterns were consistent with unstable, epidemic transmission,
      amenable to targeted intervention. In contrast, P. vivax diversity was higher and
      transmission appeared more stable. Population differentiation was lower in P.
      vivax versus P. falciparum, suggesting that the hypnozoite reservoir might play
      an important role in sustaining local transmission and facilitating the spread of
      P. vivax infections in different endemic settings. P. vivax polyclonality varied
      with local endemicity, demonstrating potential utility in informing on
      transmission intensity in this species. CONCLUSIONS/SIGNIFICANCE: Molecular
      approaches can provide important information on malaria transmission that is not
      readily available from traditional epidemiological measures. Elucidation of the
      transmission dynamics circulating in a given setting will have a major role in
      prioritising malaria control strategies, particularly against the relatively
      neglected non-falciparum species.

PMID- 25951187
TI  - Candidate Gene Polymorphisms and their Association with Glycogen Content in the
      Pacific Oyster Crassostrea gigas.
AB  - BACKGROUND: The Pacific oyster Crassostrea gigas is an important cultivated
      shellfish that is rich in nutrients. It contains high levels of glycogen, which
      is of high nutritional value. To investigate the genetic basis of this high
      glycogen content and its variation, we conducted a candidate gene association
      analysis using a wild population, and confirmed our results using an independent
      population, via targeted gene resequencing and mRNA expression analysis. RESULTS:
      We validated 295 SNPs in the 90 candidate genes surveyed for association with
      glycogen content, 86 of were ultimately genotyped in all 144 experimental
      individuals from Jiaonan (JN). In addition, 732 SNPs were genotyped via targeted
      gene resequencing. Two SNPs (Cg_SNP_TY202 and Cg_SNP_3021) in Cg_GD1 (glycogen
      debranching enzyme) and one SNP (Cg_SNP_4) in Cg_GP1 (glycogen phosphorylase)
      were identified as being associated with glycogen content. The glycogen content
      of individuals with genotypes TT and TC in Cg_SNP_TY202 was higher than that of
      individuals with genotype CC. The transcript abundance of both glycogen
      associated genes was differentially expressed in high glycogen content and low
      glycogen content individuals. CONCLUSIONS: This study identified three
      polymorphisms in two genes associated with oyster glycogen content, via candidate
      gene association analysis. The transcript abundance differences in Cg_GD1 and
      Cg_GP1 between low- and the high-glycogen content individuals suggests that it is
      possible that transcript regulation is mediated by variations of Cg_SNP_TY202,
      Cg_SNP_3021, and Cg_SNP_4. These findings will not only provide insights into the
      genetic basis of oyster quality, but also promote research into the molecular
      breeding of oysters.

PMID- 25951189
TI  - Cancer and "bad luck": risk perception, decision making, and risk-reducing
      behavior.

PMID- 25951188
TI  - A Two-Stepped Culture Method for Efficient Production of Trichogenic
      Keratinocytes.
AB  - Successful hair follicle (HF) neogenesis in adult life depends on the existence
      of both capable dermal cells and competent epidermal keratinocytes that
      recapitulate embryonic organogenesis through epithelial-mesenchymal interaction.
      In tissue engineering, the maintenance of trichogenic potential of adult
      epidermal cells, while expanding them remains a challenging issue. We found that
      although HF outer root sheath keratinocytes could be expanded for more than 100
      passages as clonogenic cells without losing the proliferative potential with a
      3T3J2 fibroblast feeder layer, these keratinocytes were unable to form new HFs
      when combined with inductive HF dermal papilla (DP) cells. However, when these
      high-passage keratinocytes were cocultured with HF DP cells for 4 days in vitro,
      they regained the trichogenic ability to form new HFs after transplantation. We
      found that the short-term coculture with DP cells enhanced both Wnt/beta-catenin
      signaling, a signaling cascade key to HF development, and upregulated the
      expression of HF-specific genes, including K6, K16, K17, and K75, in
      keratinocytes, indicating that these cells were poised toward a HF fate. Hence,
      efficient production of trichogenic keratinocytes can be obtained by a two
      stepped procedure with initial cell expansion with a 3T3J2 fibroblast feeder
      followed by short-term coculture with DP cells. 

PMID- 25951186
TI  - The Zinc-Finger Antiviral Protein ZAP Inhibits LINE and Alu Retrotransposition.
AB  - Long INterspersed Element-1 (LINE-1 or L1) is the only active autonomous
      retrotransposon in the human genome. To investigate the interplay between the L1
      retrotransposition machinery and the host cell, we used co-immunoprecipitation in
      conjunction with liquid chromatography and tandem mass spectrometry to identify
      cellular proteins that interact with the L1 first open reading frame-encoded
      protein, ORF1p. We identified 39 ORF1p-interacting candidate proteins including
      the zinc-finger antiviral protein (ZAP or ZC3HAV1). Here we show that the
      interaction between ZAP and ORF1p requires RNA and that ZAP overexpression in
      HeLa cells inhibits the retrotransposition of engineered human L1 and Alu
      elements, an engineered mouse L1, and an engineered zebrafish LINE-2 element.
      Consistently, siRNA-mediated depletion of endogenous ZAP in HeLa cells led to a
      ~2-fold increase in human L1 retrotransposition. Fluorescence microscopy in
      cultured human cells demonstrated that ZAP co-localizes with L1 RNA, ORF1p, and
      stress granule associated proteins in cytoplasmic foci. Finally, molecular
      genetic and biochemical analyses indicate that ZAP reduces the accumulation of
      full-length L1 RNA and the L1-encoded proteins, yielding mechanistic insight
      about how ZAP may inhibit L1 retrotransposition. Together, these data suggest
      that ZAP inhibits the retrotransposition of LINE and Alu elements. 

PMID- 25951192
TI  - Instantaneous hydrolysis of nerve-agent simulants with a six-connected zirconium
      based metal-organic framework.
AB  - A nerve-agent simulant based on a phosphate ester is hydrolyzed using a MOF-based
      catalyst. Suspensions of MOF-808 (6-connected), a material featuring 6-connected
      zirconium nodes, display the highest hydrolysis rates among all MOFs that have
      been reported to date. A plug-flow reactor was also prepared with MOF-808 (6
      connected) as the active layer. Deployed in a simple filtration scheme, the
      reactor displayed high hydrolysis efficiency and reusability. 

PMID- 25951190
TI  - Networks in Coronary Heart Disease Genetics As a Step towards Systems
      Epidemiology.
AB  - We present the use of innovative machine learning techniques in the understanding
      of Coronary Heart Disease (CHD) through intermediate traits, as an example of the
      use of this class of methods as a first step towards a systems epidemiology
      approach of complex diseases genetics. Using a sample of 252 middle-aged men, of
      which 102 had a CHD event in 10 years follow-up, we applied machine learning
      algorithms for the selection of CHD intermediate phenotypes, established markers,
      risk factors, and their previously associated genetic polymorphisms, and
      constructed a map of relationships between the selected variables. Of the 52
      variables considered, 42 were retained after selection of the most informative
      variables for CHD. The constructed map suggests that most selected variables were
      related to CHD in a context dependent manner while only a small number of
      variables were related to a specific outcome. We also observed that loss of
      complexity in the network was linked to a future CHD event. We propose that
      novel, non-linear, and integrative epidemiological approaches are required to
      combine all available information, in order to truly translate the new advances
      in medical sciences to gains in preventive measures and patients care. 

PMID- 25951191
TI  - High Affinity Antibodies against Influenza Characterize the Plasmablast Response
      in SLE Patients After Vaccination.
AB  - Breakdown of B cell tolerance is a cardinal feature of systemic lupus
      erythematosus (SLE). Increased numbers of autoreactive mature naive B cells have
      been described in SLE patients and autoantibodies have been shown to arise from
      autoreactive and non-autoreactive precursors. How these defects, in the
      regulation of B cell tolerance and selection, influence germinal center (GC)
      reactions that are directed towards foreign antigens has yet to be investigated.
      Here, we examined the characteristics of post-GC foreign antigen-specific B cells
      from SLE patients and healthy controls by analyzing monoclonal antibodies
      generated from plasmablasts induced specifically by influenza vaccination. We
      report that many of the SLE patients had anti-influenza antibodies with higher
      binding affinity and neutralization capacity than those from controls. Although
      overall frequencies of autoreactivity in the influenza-specific plasmablasts were
      similar for SLE patients and controls, the variable gene repertoire of influenza
      specific plasmablasts from SLE patients was altered, with increased usage of JH6
      and long heavy chain CDR3 segments. We found that high affinity anti-influenza
      antibodies generally characterize the plasmablast responses of SLE patients with
      low levels of autoreactivity; however, certain exceptions were noted. The high
      avidity antibody responses in SLE patients may also be correlated with cytokines
      that are abnormally expressed in lupus. These findings provide insights into the
      effects of dysregulated immunity on the quality of antibody responses following
      influenza vaccination and further our understanding of the underlying
      abnormalities of lupus. 

PMID- 25951194
TI  - Correction: Enhanced Photoluminescence and Raman Properties of Al-Doped ZnO
      Nanostructures Prepared Using Thermal Chemical Vapor Deposition of Methanol
      Assisted with Heated Brass.

PMID- 25951193
TI  - The integral membrane protein ITM2A, a transcriptional target of PKA-CREB,
      regulates autophagic flux via interaction with the vacuolar ATPase.
AB  - The PKA-CREB signaling pathway is involved in many cellular processes including
      autophagy. Recent studies demonstrated that PKA-CREB inhibits autophagy in yeast;
      however, the role of PKA-CREB signaling in mammalian cell autophagy has not been
      fully characterized. Here, we report that the integral membrane protein ITM2A
      expression is positively regulated by PKA-CREB signaling and ITM2A expression
      interferes with autophagic flux by interacting with vacuolar ATPase (v-ATPase).
      The ITM2A promoter contains a CRE element, and mutation at the CRE consensus site
      decreases the promoter activity. Forskolin treatment and PKA expression activate
      the ITM2A promoter confirming that ITM2A expression is dependent on the PKA-CREB
      pathway. ITM2A expression results in the accumulation of autophagosomes and
      interferes with autolysosome formation by blocking autophagic flux. We
      demonstrated that ITM2A physically interacts with v-ATPase and inhibits lysosomal
      function. These results support the notion that PKA-CREB signaling pathway
      regulates ITM2A expression, which negatively regulates autophagic flux by
      interfering with the function of v-ATPase. 

PMID- 25951195
TI  - cAMP-Signalling Regulates Gametocyte-Infected Erythrocyte Deformability Required
      for Malaria Parasite Transmission.
AB  - Blocking Plasmodium falciparum transmission to mosquitoes has been designated a
      strategic objective in the global agenda of malaria elimination. Transmission is
      ensured by gametocyte-infected erythrocytes (GIE) that sequester in the bone
      marrow and at maturation are released into peripheral blood from where they are
      taken up during a mosquito blood meal. Release into the blood circulation is
      accompanied by an increase in GIE deformability that allows them to pass through
      the spleen. Here, we used a microsphere matrix to mimic splenic filtration and
      investigated the role of cAMP-signalling in regulating GIE deformability. We
      demonstrated that mature GIE deformability is dependent on reduced cAMP
      signalling and on increased phosphodiesterase expression in stage V gametocytes,
      and that parasite cAMP-dependent kinase activity contributes to the stiffness of
      immature gametocytes. Importantly, pharmacological agents that raise cAMP levels
      in transmissible stage V gametocytes render them less deformable and hence less
      likely to circulate through the spleen. Therefore, phosphodiesterase inhibitors
      that raise cAMP levels in P. falciparum infected erythrocytes, such as
      sildenafil, represent new candidate drugs to block transmission of malaria
      parasites. 

PMID- 25951198
TI  - An artificial bioindicator system for network intrusion detection.
AB  - An artificial bioindicator system is developed in order to solve a network
      intrusion detection problem. The system, inspired by an ecological approach to
      biological immune systems, evolves a population of agents that learn to survive
      in their environment. An adaptation process allows the transformation of the
      agent population into a bioindicator that is capable of reacting to system
      anomalies. Two characteristics stand out in our proposal. On the one hand, it is
      able to discover new, previously unseen attacks, and on the other hand, contrary
      to most of the existing systems for network intrusion detection, it does not need
      any previous training. We experimentally compare our proposal with three state-of
      the-art algorithms and show that it outperforms the competing approaches on
      widely used benchmark data. 

PMID- 25951196
TI  - Variation in functional connectivity along anterior-to-posterior intraparietal
      sulcus, and relationship with age across late childhood and adolescence.
AB  - The intraparietal sulcus (IPS), a region in the dorsal attention network (DAN),
      has been implicated in multi-sensory attention and working memory. Working memory
      and attention develop across childhood; changes in functional connectivity within
      the DAN may relate to this maturation. Previous findings regarding fronto
      parietal intrinsic functional connectivity age-effects were mixed. Our study
      aimed to circumvent limitations of previous work using a large cross-sectional
      sample, 183 typically developing participants 6.5-20 years, from the Autism Brain
      Imaging Data Exchange, and seed regions along the anterior-to-posterior axis of
      the IPS. These seeds, IPS0-4, were entered into functional connectivity models.
      Group-level models investigated differential connectivity along the IPS and
      relationships with age. Anterior IPS3/4 exhibited greater connectivity with
      sensorimotor/pre-motor regions. Posterior IPS0/1 demonstrated greater
      connectivity with dorsal and ventral visual regions. Positive age-effects were
      found between IPS3-4 and visual regions. Negative age-effects were found between
      IPS and superior parietal and medial orbitofrontal cortices. Follow-up region of
      interest analyses were used to estimate age-effects for DAN and anticorrelated
      default mode network regions. Results suggest age-effects on IPS functional
      connectivity are relatively modest, and may differ pre- and across-adolescence.
      Studying typical age-related connectivity variability within this network may
      help to understand neurodevelopmental disorders marked by impaired attention. 

PMID- 25951197
TI  - Self-reported household impacts of large-scale chemical contamination of the
      public water supply, Charleston, West Virginia, USA.
AB  - A January 2014 industrial accident contaminated the public water supply of
      approximately 300,000 homes in and near Charleston, West Virginia (USA) with low
      levels of a strongly-smelling substance consisting principally of 4
      methylcyclohexane methanol (MCHM). The ensuing state of emergency closed schools
      and businesses. Hundreds of people sought medical care for symptoms they related
      to the incident. We surveyed 498 households by telephone to assess the episode's
      health and economic impact as well as public perception of risk communication by
      responsible officials. Thirty two percent of households (159/498) reported
      someone with illness believed to be related to the chemical spill, chiefly
      dermatological or gastrointestinal symptoms. Respondents experienced more
      frequent symptoms of psychological distress during and within 30 days of the
      emergency than 90 days later. Sixty-seven respondent households (13%) had someone
      miss work because of the crisis, missing a median of 3 days of work. Of 443
      households reporting extra expenses due to the crisis, 46% spent less than $100,
      while 10% spent over $500 (estimated average about $206). More than 80% (401/485)
      households learned of the spill the same day it occurred. More than 2/3 of
      households complied fully with "do not use" orders that were issued; only 8%
      reported drinking water against advice. Household assessments of official
      communications varied by source, with local officials receiving an average "B"
      rating, whereas some federal and water company communication received a "D"
      grade. More than 90% of households obtained safe water from distribution centers
      or stores during the emergency. We conclude that the spill had major economic
      impact with substantial numbers of individuals reporting incident-related
      illnesses and psychological distress. Authorities were successful supplying
      emergency drinking water, but less so with risk communication. 

PMID- 25951199
TI  - Learning tensegrity locomotion using open-loop control signals and coevolutionary
      algorithms.
AB  - Soft robots offer many advantages over traditional rigid robots. However, soft
      robots can be difficult to control with standard control methods. Fortunately,
      evolutionary algorithms can offer an elegant solution to this problem. Instead of
      creating controls to handle the intricate dynamics of these robots, we can simply
      evolve the controls using a simulation to provide an evaluation function. In this
      article, we show how such a control paradigm can be applied to an emerging field
      within soft robotics: robots based on tensegrity structures. We take the model of
      the Spherical Underactuated Planetary Exploration Robot ball (SUPERball), an
      icosahedron tensegrity robot under production at NASA Ames Research Center,
      develop a rolling locomotion algorithm, and study the learned behavior using an
      accurate model of the SUPERball simulated in the NASA Tensegrity Robotics
      Toolkit. We first present the historical-average fitness-shaping algorithm for
      coevolutionary algorithms to speed up learning while favoring robustness over
      optimality. Second, we use a distributed control approach by coevolving open-loop
      control signals for each controller. Being simple and distributed, open-loop
      controllers can be readily implemented on SUPERball hardware without the need for
      sensor information or precise coordination. We analyze signals of different
      complexities and frequencies. Among the learned policies, we take one of the best
      and use it to analyze different aspects of the rolling gait, such as lengths,
      tensions, and energy consumption. We also discuss the correlation between the
      signals controlling different parts of the tensegrity robot. 

PMID- 25951200
TI  - On the Evolution of Behaviors through Embodied Imitation.
AB  - This article describes research in which embodied imitation and behavioral
      adaptation are investigated in collective robotics. We model social learning in
      artificial agents with real robots. The robots are able to observe and learn each
      others' movement patterns using their on-board sensors only, so that imitation is
      embodied. We show that the variations that arise from embodiment allow certain
      behaviors that are better adapted to the process of imitation to emerge and
      evolve during multiple cycles of imitation. As these behaviors are more robust to
      uncertainties in the real robots' sensors and actuators, they can be learned by
      other members of the collective with higher fidelity. Three different types of
      learned-behavior memory have been experimentally tested to investigate the effect
      of memory capacity on the evolution of movement patterns, and results show that
      as the movement patterns evolve through multiple cycles of imitation, selection,
      and variation, the robots are able to, in a sense, agree on the structure of the
      behaviors that are imitated. 

PMID- 25951201
TI  - Minimal conditions for protocell stationary growth.
AB  - We show that self-replication of a chemical system encapsulated within a membrane
      growing from within is possible without any explicit feature such as
      autocatalysis or metabolic closure, and without the need for their emergence
      through complexity. We use a protocell model relying upon random conservative
      chemical reaction networks with arbitrary stoichiometry, and we investigate the
      protocell's capability for self-replication, for various numbers of reactions in
      the network. We elucidate the underlying mechanisms in terms of simple minimal
      conditions pertaining only to the topology of the embedded chemical reaction
      network. A necessary condition is that each moiety must be fed, and a sufficient
      condition is that each siphon is fed. Although these minimal conditions are
      purely topological, by further endowing conservative chemical reaction networks
      with thermodynamically consistent kinetics, we show that the growth rate tends to
      increase on increasing the Gibbs energy per unit molecular weight of the nutrient
      and on decreasing that of the membrane precursor. 

PMID- 25951203
TI  - Primary vaginal cancer after hysterectomy.
AB  - OBJECTIVES: We sought to examine the patients who developed vaginal cancer after
      prior hysterectomy and to determine whether any of these cancers could have been
      prevented. METHODS: The records of patients treated with vaginal cancer over a 15
      year period in the Department of Gynecologic Oncology at the Mercy Hospital for
      Women were reviewed. Those patients who had developed a vaginal cancer after
      hysterectomy between 1980 and 1994 were identified. RESULTS: A total of 1,511
      primary gynecological cancers were treated between 1980 and 1994, and 23 (1.5%)
      were primary vaginal cancers. Of these 23 patients, 13 had had a prior
      hysterectomy (57%). Four of the 13 patients (31%) were asymptomatic and presented
      after routine vault smears, and 9 were symptomatic and were diagnosed after
      further investigation. All 13 patients had squamous cell cancers. Two patients
      had had a history of cervical intraepithelial neoplasia (CIN) grade 3 reported on
      cervical smear but not been accounted for, both cone biopsy and hysterectomy
      having found no histological abnormality. CONCLUSIONS: Primary vaginal cancer is
      uncommon. After hysterectomy, vaginal vault cytology should continue to be
      performed if high-risk factors, such as history of lower genital tract neoplasia,
      are present. The two patients with unaccounted-for CIN3 reported on Papanicolaou
      smear may have had undiagnosed vaginal intraepithelial neoplasia grade 3 (not
      CIN3) resulting in vaginal cancers 10 and 15 years later. Therefore, when
      colposcopy is being performed to investigate an abnormal Pap smear, the entire
      lower genital tract always should be examined.

PMID- 25951204
TI  - The clinical significance of cervical atypical squamous cells of undetermined
      significance: analysis of 200 patients with long-term follow-up.
AB  - BACKGROUND: Two hundred premenopausal middle- or upper-income women in monogamous
      relationships and without a history of cervical intraepithelial neoplasia or
      genital human papillomavirus infection underwent prospective evaluation for
      repetitive atypical squamous cells of undetermined significance Papanicolaou
      (Pap) cervical smears. RESULTS: Only two patients were found to have or developed
      high-grade squamous intraepithelial lesions after 2 years of follow-up. Only 10
      patients had or developed lowgrade squamous intraepithelial lesions. CONCLUSIONS:
      The usefulness of the atypical squamous cells of undetermined significance
      category in detecting cervical high-grade squamous intraepithelial lesions
      appears to be of limited value in this patient population.

PMID- 25951205
TI  - Atypical squamous cells of undetermined significance in a high-risk population.
AB  - OBJECTIVES: We set out to develop a benchmark for our use of the term atypical
      squamous cells of undetermined significance (ASCUS), to compare our ASCUS rate to
      rates reported by others, and to determine the correlation between ASCUS and
      histologically-proved cervical intraepithelial neoplasia (CIN) in our population.
      MATERIALS AND METHODS: All Papanicolaou (Pap) smears and associated cervical
      biopsies or endocervical curettages interpreted by the University of Florida
      Department of Pathology between 1992 and 1995 were reviewed. RESULTS: Of 28,494
      Pap smears; 17% were classified as "epithelial cell abnormality, squamous," with
      7.4% ASCUS, 5.6% low-grade squamous intraepithelial lesion, and 4.0% high-grade
      squamous intraepithelial lesion. Of the 2,100 ASCUS cases, 753 had timely
      biopsies; 45.8% were benign, 53.8% showed CIN, and 0.4% showed carcinoma. Of the
      CIN cases, 39.2% were CIN1, 8.1% were CIN2, and 6.5% were CIN3. CONCLUSIONS: Our
      7.4% ASCUS rate is similar to published rates. Our high rate of neoplasia
      associated with ASCUS (54.2%) and our low ASCUS-squamous intraepithelial lesion
      ratio (0.77) indicate that we do not overuse the ASCUS classification.

PMID- 25951202
TI  - High rate of subclinical chikungunya virus infection and association of
      neutralizing antibody with protection in a prospective cohort in the Philippines.
AB  - BACKGROUND: Chikungunya virus (CHIKV) is a globally re-emerging arbovirus for
      which previous studies have indicated the majority of infections result in
      symptomatic febrile illness. We sought to characterize the proportion of
      subclinical and symptomatic CHIKV infections in a prospective cohort study in a
      country with known CHIKV circulation. METHODS/FINDINGS: A prospective
      longitudinal cohort of subjects >=6 months old underwent community-based active
      surveillance for acute febrile illness in Cebu City, Philippines from 2012-13.
      Subjects with fever history were clinically evaluated at acute, 2, 5, and 8 day
      visits, and at a 3-week convalescent visit. Blood was collected at the acute and
      3-week convalescent visits. Symptomatic CHIKV infections were identified by
      positive CHIKV PCR in acute blood samples and/or CHIKV IgM/IgG ELISA
      seroconversion in paired acute/convalescent samples. Enrollment and 12-month
      blood samples underwent plaque reduction neutralization test (PRNT) using CHIKV
      attenuated strain 181/clone25. Subclinical CHIKV infections were identified by
      >=8-fold rise from a baseline enrollment PRNT titer <10 without symptomatic
      infection detected during the intervening surveillance period. Selected CHIKV PCR
      positive samples underwent viral isolation and envelope protein-1 gene
      sequencing. Of 853 subjects who completed all study procedures at 12 months, 19
      symptomatic infections (2.19 per 100 person-years) and 87 subclinical infections
      (10.03 per 100 person-years) occurred. The ratio of subclinical-to-symptomatic
      infections was 4.6:1 varying with age from 2:1 in 6 month-5 year olds to 12:1 in
      those >50 years old. Baseline CHIKV PRNT titer >=10 was associated with 100%
      (95%CI: 46.1, 100.0) protection from symptomatic CHIKV infection. Phylogenetic
      analysis demonstrated Asian genotype closely related to strains from Asia and the
      Caribbean. CONCLUSIONS: Subclinical infections accounted for a majority of total
      CHIKV infections. A positive baseline CHIKV PRNT titer was associated with
      protection from symptomatic CHIKV infection. These findings have implications for
      assessing disease burden, understanding virus transmission, and supporting
      vaccine development.

PMID- 25951206
TI  - Benefits and risks of directed biopsy in pregnancy.
AB  - OBJECTIVES: Our aim was to assess the risks of directed biopsy in pregnant women
      and to compare its reliability to that of colposcopy. METHODS: One hundred
      seventy six gravidas, whose final diagnosis could be ascertained either by the
      histological analysis of a surgical specimen or by a sufficiently informative
      postpartum follow-up, were examined by the same colposcopist. The reliability of
      colposcopy and directed biopsy were compared using the McNemar chi test for
      univariate analysis and the Mantel-Haenszel chi test for multivariate analysis.
      RESULTS: Directed biopsies were performed in 128 patients (72.7%), only 1 of whom
      experienced hemorrhage requiring vaginal packing. No other complications
      occurred, and premature labor was not more frequent after biopsy. The reliability
      of biopsy was significantly higher than that of colposcopy (82.6 vs 65.2%; p <
      .005). Among patients with accurate biopsy but discordant colposcopy, the final
      diagnosis was normal cervix, low-grade cervical intraepithelial neoplasia (CIN),
      high-grade CIN, and cancer in 48.4, 29.0, 22.6, and 0% of cases, respectively.
      When results were stratified by final diagnosis, biopsy was no more accurate than
      was colposcopy, regardless of cytological findings, colposcopic impression,
      gestational age, parity, or colposcopist's experience. One of the two occult
      invasive cancers correctly diagnosed by biopsy had an unsatisfactory colposcopy
      suggesting invasion. CONCLUSIONS: The difficulties of colposcopy during pregnancy
      and the minimal risks of directed biopsy justify a biopsy in gravidas when either
      cytology or colposcopy suggests at least a high-grade CIN, to ensure that no
      cancer has been overlooked.

PMID- 25951208
TI  - Treatment of cervical intraepithelial neoplasia in a prospective study comparing
      large-loop excision of the transformation zone, laser vaporization, and knife
      cone biopsy.
AB  - OBJECTIVE: Our aim was to compare cervical intraepithelial neoplasia (CIN)
      treatment results in the use of large-loop excision of the transformation zone
      (LLETZ), laser vaporization, and cold-knife cone biopsy. MATERIALS AND METHODS:
      We included in the study patients with CIN lesions diagnosed at the Hospital
      Universitario Materno-Infantil Vall d'Hebron and Hospital Clinic i Provincial de
      Barcelona, Barcelona, Spain, between March 1991 and March 1994. Patients with
      unsatisfactory colposcopy were excluded from the study. One hundred twenty-three
      patients were included in this study: 98 patients were compared for LLETZ
      treatment versus laser vaporization, and 69 CIN3 patients were compared for three
      treatments: LLETZ, laser vaporization, and knife cone biopsy. Patients were
      followed at 3-month intervals for at least 1 year. Follow-up included physical
      examination, cervical Papanicolaou (Pap) smear, cervical colposcopy, and a
      colposcopically guided biopsy when required. Treatment failure (persistence or
      recurrence) was defined by the presence of CIN confirmed histologically by a
      colposcopically guided biopsy. RESULTS: The mean age of patients was 34.1 years.
      The agreement between histology from the colposcopically guided biopsy and the
      surgical specimen was 60%, and the kappa coefficient was 40.7% (moderate
      agreement). Three cases of microinvasive carcinoma were diagnosed in patients
      whose initial diagnosis was CIN3 on colpobiopsy (4% of invasion in the initial
      CIN3 group of patients). In a comparison of LLETZ with laser treatment for all
      CIN grades, the unique independent prognostic factor for persistence-recurrence
      of the disease was the colposcopic size of the primary lesion (relative risk,
      4.9; Cl, 1.33-18.45). CONCLUSIONS: We conclude that the LLETZ procedure for CIN
      treatment demonstrates an advantage over destructive methods for detection of
      occult microinvasive and invasive cancer. This process is a simple outpatient
      technique with the same failure as that of laser vaporization in all CIN grades.
      In the treatment of CIN3, cold-knife cone biopsy had better cure rates. Close
      follow-up is required in these patients, because of their risk of developing
      recurrent CIN or invasive carcinoma.

PMID- 25951207
TI  - The efficacy of topical benzocaine gel in providing anesthesia prior to cervical
      biopsy and endocervical curettage.
AB  - OBJECTIVES: Our goal was to determine the effectiveness of topical 20% benzocaine
      gel in providing anesthesia prior to cervical biopsy and endocervical curettage
      (ECC) and to identify specific patient characteristics that would predict which
      patients would be more likely to benefit from the application of benzocaine gel
      before cervical procedures. MATERIALS AND METHODS: Women requiring cervical
      biopsy and ECC completed a questionnaire that obtained demographical and
      pertinent gynecological information, perceived pain thresholds, and anxiety
      levels prior to the cervical biopsy procedures. Either benzocaine gel or a
      placebo was applied to the ectocervix and endocervical canal in a doubleblinded
      fashion. After each procedure, subjects reported the type, intensity, character,
      and duration of the sensation via visual analog scales (VAS) (0 = no sensation,
      100 = maximum sensation). RESULTS: No difference was noted in the mean VAS scores
      reported by the placebo and benzocaine cohorts for the sensation felt at the time
      of cervical biopsy (30.1 SD +/- 28.2 and 35.3 SD +/- 24.3, respectively; p =
      .33). No significant difference in mean VAS scores was noted after ECC by the
      placebo cohort (53.0 SD +/- 26.8) and the benzocaine cohort (41.0 SD +/- 28.2; p
      = .09). Pain experienced with prior Papanicolaou (Pap) smears correlated
      significantly with the level of sensation noted during cervical biopsy (r =
      0.395; p = .0001). The mean VAS scores for sensation experienced during cervical
      biopsy also were significantly greater among women who reported a history of
      dyspareunia (42.2 vs 27.7; p = .0059) and who reported a history of painful
      pelvic examinations (45.0 vs 29.8; p = .0125) than among women who did not report
      these painful experiences. CONCLUSIONS: Topical benzocaine gel was ineffective in
      reducing discomfort reported on cervical biopsy and ECC as compared with a
      placebo. Biopsy instrument sharpness may be a critically important factor that
      determines invoked pain. Discomfort associated with prior Pap smears, history of
      dyspareunia, and history of painful pelvic examinations correlated significantly
      with a greater perceived biopsy sensation. Prebiopsy recognition of these
      indicators may help clinicians to determine which women may be more likely to
      experience greater pain with cervical biopsy and enable them to intervene with
      other pain prevention measures.

PMID- 25951209
TI  - High-risk human papillomavirus testing of women with cytological low-grade
      squamous intraepithelial lesions.
AB  - BACKGROUND: Testing for carcinogenic human papillomavirus (HPV) types has been
      suggested to evaluate patients with atypical squamous cells of unknown
      significance. We wanted to know whether this test was clinically useful in
      patients with low-grade squamous intraepithelial lesions (SIL) detected by
      Papanicoloau (Pap) smear. METHODS AND MATERIALS: We tested 159 women with low
      grade SIL Pap smears for high-risk HPV types, using the Hybrid Capture HPV DNA
      Assay (Digene Corp., Silver Springs, MD) during evaluation by colposcopy and
      cervical biopsies. We constructed a receiver-operating characteristic curve and
      calculated sensitivity, specificity, and predictive values for the presence of
      high-risk virus and cervical intraepithelial neoplasia (CIN). RESULTS: The
      receiver-operating characteristic curve suggested that 3.0 relative light units
      was the best cutoff for a positive test, rather than the manufacturer-recommended
      1.0 relative light units. The sensitivity for detecting CIN was 0.858 [95%
      confidence interval (Cl); 0.792-0.925] and specificity was 0.623 (95% Cl, 0.492
      0.753). The pretest probability of CIN was 0.667 in this group of patients, and
      the positive predictive value was 0.820. CONCLUSION: The Hybrid Capture HPV DNA
      Assay is of limited use in predicting those low-grade SIL Pap smears will have
      histologically confirmed CIN.

PMID- 25951211
TI  - General considerations.

PMID- 25951210
TI  - Expression of p16INK4 and Rb Genes in Cervical Neoplasm.
AB  - BACKGROUND: The molecular events surrounding the pathogenesis of human cervical
      cancer remain to be defined to a significant extent. The current study
      investigates the expression of two putative tumor suppressor genes p16 and Rb in
      cervical neoplasm. MATERIALS AND METHODS: Tissue was collected from 16 cervical
      intraepithelial neoplasia (CIN) patients and 91 cervical cancer patients prior to
      definitive treatment. Immunohistochemical staining for p16 and Rb protein was
      performed in these cases to determine the relationship between the expression of
      these two genes in premalignant and malignant neoplasias of the cervix. RESULTS:
      Eight (50%) CIN and 9 (10%) of cervical carcinoma cases lacked p16 expression,
      while 4 CIN (25%) and 34 carcinoma (37%) cases did not display Rb expression. The
      prevalence of negative p16 expression in CIN was significantly higher than in
      cervical carcinoma (p < .01). The prevalence of negative Rb expression was higher
      than was negative p16 expression in cervical carcinoma (p < .01). Alterations of
      p16 and Rb are relatively exclusive in both CIN and carcinoma (p < .01). No
      statistically significant relationship was found between either p16 or Rb
      expression and tumor cell type, histological grade, or clinical stage in cervical
      carcinoma. CONCLUSIONS: Deficiency of either p16 or Rb protein appears to be
      contributory to oncogenesis of cervical neoplasm in different subgroups of
      patients. Whether negative p16 expression commonly is involved in the
      pathogenesis of CIN must be confirmed.

PMID- 25951212
TI  - Is LEEP the Cesarean Delivery of Cervical Intraepithelial Neoplasia?

PMID- 25951213
TI  - Small-Cell Carcinoma of the Cervix Presenting with Severe Hypokalemia as a
      Manifestation of Cushing's Syndrome.
AB  - OBJECTIVES: A case of small-cell carcinoma of the cervix and severe hypokalemia
      is presented. The need for surveillance of paraneoplastic syndromes in these
      patients is emphasized. METHODS: The patient's clinical course is presented. The
      available literature regarding small-cell carcinoma of the cervix and Cushing's
      syndrome is reviewed. RESULTS: A 32-year-old woman had diagnosed small-cell
      carcinoma after simple hysterectomy. After radical parametrectomy, she developed
      liver metastases that did not respond to chemotherapy. Subsequently, she
      developed severe and unremitting hypokalemia, which was determined to be the
      initial manifestation of Cushing's syndrome secondary to ectopic
      adenocorticotropic hormone production. Typical clinical features of Cushing's
      syndrome were noted to arise during subsequent examinations. CONCLUSIONS: Though
      paraneoplastic syndromes associated with small-cell carcinoma of the cervix are
      rare, this case report describes one of these syndromes as an etiology for
      metabolic derangements.

PMID- 25951214
TI  - Home study course: autumn 1997.
AB  - ? OBJECTIVE: : The Home Study Course is intended for the practicing colposcopist
      or practitioner who is seeking to develop or enhance his or her colposcopic
      skills. The goal of the course is to present colposcopic cases that are unusual
      or instructive in terms of appearance, presentation, or management, or that
      demonstrate new and important knowledge in the area of colposcopy or pathology.
      Participants may benefit from reading and studying the material or from testing
      their knowledge by answering the questions. ? ACCME ACCREDITATION: : The American
      Society for Colposcopy and Cervical Pathology (ASCCP) is accredited by the
      Accreditation Council for Continuing Medical Education (ACCME) to sponsor
      continuing medical education for physicians. The ASCCP designates this continuing
      medical education activity for 1 credit hour in Category I of the Physicians'
      Recognition Award of the American Medical Association. Credit is available for
      those who choose to apply.The Home Study Course is planned and produced in
      accordance with the ACCME's Essentials.

PMID- 25951216
TI  - The american society for colposcopy and cervical pathology.

PMID- 25951215
TI  - Evolution of therapeutic approaches to cervical intraepithelial neoplasia.
AB  - ? ABSTRACT: : The site of origin of cervical intraepithelial neoplasia (CIN) and
      the histological distribution of the disease are the most important factors in
      understanding the correct method to evaluate CIN. Changes in terminology from the
      CIN classification to the Bethesda squamous intraepithelial lesion definitions
      also influence the approach to treatment. Lowgrade lesions are not treated; high
      grade lesions are treated. ?.

PMID- 25951217
TI  - How do you evaluate an atypical glandular cell papanicolaou smear with psammoma
      bodies present?

PMID- 25951219
TI  - Response 3.

PMID- 25951218
TI  - Response 2.

PMID- 25951220
TI  - Recurrent genital intraepithelial neoplasia.

PMID- 25951221
TI  - Response 1.

PMID- 25951222
TI  - Response 2.

PMID- 25951223
TI  - Response 3.

PMID- 25951224
TI  - Response 4.

PMID- 25951225
TI  - Items of interest.

PMID- 25951226
TI  - Olefin oxygenation by water on an iridium center.
AB  - Oxygenation of 1,5-cyclooctadiene (COD) is achieved on an iridium center using
      water as a reagent. A hydrogen-bonding interaction with an unbound nitrogen atom
      of the naphthyridine-based ligand architecture promotes nucleophilic attack of
      water to the metal-bound COD. Irida-oxetane and oxo-irida-allyl compounds are
      isolated, products which are normally accessed from reactions with H2O2 or O2.
      DFT studies support a ligand-assisted water activation mechanism. 

PMID- 25951227
TI  - Transcranial Electrical Stimulation over Dorsolateral Prefrontal Cortex Modulates
      Processing of Social Cognitive and Affective Information.
AB  - Recent neurofunctional studies suggested that lateral prefrontal cortex is a
      domain-general cognitive control area modulating computation of social
      information. Neuropsychological evidence reported dissociations between cognitive
      and affective components of social cognition. Here, we tested whether performance
      on social cognitive and affective tasks can be modulated by transcranial direct
      current stimulation (tDCS) over dorsolateral prefrontal cortex (DLPFC). To this
      aim, we compared the effects of tDCS on explicit recognition of emotional facial
      expressions (affective task), and on one cognitive task assessing the ability to
      adopt another person's visual perspective. In a randomized, cross-over design,
      male and female healthy participants performed the two experimental tasks after
      bi-hemispheric tDCS (sham, left anodal/right cathodal, and right anodal/left
      cathodal) applied over DLPFC. Results showed that only in male participants
      explicit recognition of fearful facial expressions was significantly faster after
      anodal right/cathodal left stimulation with respect to anodal left/cathodal right
      and sham stimulations. In the visual perspective taking task, instead, anodal
      right/cathodal left stimulation negatively affected both male and female
      participants' tendency to adopt another's point of view. These findings
      demonstrated that concurrent facilitation of right and inhibition of left lateral
      prefrontal cortex can speed-up males' responses to threatening faces whereas it
      interferes with the ability to adopt another's viewpoint independently from
      gender. Thus, stimulation of cognitive control areas can lead to different
      effects on social cognitive skills depending on the affective vs. cognitive
      nature of the task, and on the gender-related differences in neural organization
      of emotion processing. 

PMID- 25951228
TI  - Effects of intermedin on dorsal root ganglia in the transmission of neuropathic
      pain in chronic constriction injury rats.
AB  - Neuropathic pain is a common and severely disabling state that affects millions
      of people worldwide. The P2X3 receptor plays a crucial role in facilitating pain
      transmission. Intermedin (IMD), which is also known as adrenomedullin 2 (AMD2) is
      a newly discovered hormone that is a member of the calcitonin/calcitonin gene
      related peptide family. The present research investigates the effects of IMD on
      pain transmission in neuropathic pain states as mediated by P2X3 receptors in
      dorsal root ganglia (DRG). Chronic constriction injury (CCI) rats were used as
      the neuropathic pain model. Adult male Sprague-Dawley rats were randomly assigned
      to five groups as follows: blank control group (Control), sham operation group
      (Sham), CCI rats treated with saline group (CCI+NS), CCI rats treated with IMD1
      53 group (CCI+IMD1-53 ), and CCI rats treated with IMD inhibitor IMD14-47 group
      (CCI+IMD14-47 ). The mechanical withdrawal threshold (MWT) was tested by the von
      Frey method, and the thermal withdrawal latency (TWL) was tested via automatic
      thermal stimulus instruments. Changes in the expression of P2X3 receptors and IMD
      in CCI rat L4/L5 DRG were detected using immunohistochemistry, reverse
      transcription-polymerase chain reaction, and Western blotting. After treatment
      with intrathecal injection (i.t.), mechanical and thermal hyperalgesia in the
      CCI+IMD1-53 group was maintained, but MWT and TWL in the CCI+IMD14-47 groups
      increased. The expression levels of P2X3 receptors and IMD in L4/L5 DRG in the
      CCI+NS and CCI+IMD1-53 groups were significantly increased compared with those in
      the Control group or the Sham group. After application of IMD14-47 in CCI rats,
      there was a decrease in the expression levels of P2X3 receptors and IMD in L4/L5
      DRG. The phosphorylation of p38 and ERK1/2 in L4/L5 DRG in the CCI+NS group and
      the CCI+IMD1-53 group was stronger than that in the Control group or the Sham
      group; however, the phosphorylation of p38 and ERK1/2 in the CCI+IMD14-47 group
      was much lower than that in the CCI+NS group or the CCI+IMD1-53 group. Our
      findings indicate that IMD might increase the sensitization effects of IMD on
      P2X3 receptors to alleviate chronic neuropathic pain injury. The IMD agonist IMD1
      53 might enhance nociceptive responses mediated by P2X3 receptors in neuropathic
      pain, and the IMD inhibitor IMD14-47 could inhibit the sensitization of the P2X3
      receptor in chronic neuropathic pain injury.

PMID- 25951229
TI  - Drosophila spaghetti and doubletime link the circadian clock and light to
      caspases, apoptosis and tauopathy.
AB  - While circadian dysfunction and neurodegeneration are correlated, the mechanism
      for this is not understood. It is not known if age-dependent circadian
      dysfunction leads to neurodegeneration or vice-versa, and the proteins that
      mediate the effect remain unidentified. Here, we show that the knock-down of a
      regulator (spag) of the circadian kinase Dbt in circadian cells lowers Dbt levels
      abnormally, lengthens circadian rhythms and causes expression of activated
      initiator caspase (Dronc) in the optic lobes during the middle of the day or
      after light pulses at night. Likewise, reduced Dbt activity lengthens circadian
      period and causes expression of activated Dronc, and a loss-of-function mutation
      in Clk also leads to expression of activated Dronc in a light-dependent manner.
      Genetic epistasis experiments place Dbt downstream of Spag in the pathway, and
      Spag-dependent reductions of Dbt are shown to require the proteasome.
      Importantly, activated Dronc expression due to reduced Spag or Dbt activity
      occurs in cells that do not express the spag RNAi or dominant negative Dbt and
      requires PDF neuropeptide signaling from the same neurons that support behavioral
      rhythms. Furthermore, reduction of Dbt or Spag activity leads to Dronc-dependent
      Drosophila Tau cleavage and enhanced neurodegeneration produced by human Tau in a
      fly eye model for tauopathy. Aging flies with lowered Dbt or Spag function show
      markers of cell death as well as behavioral deficits and shortened lifespans, and
      even old wild type flies exhibit Dbt modification and activated caspase at
      particular times of day. These results suggest that Dbt suppresses expression of
      activated Dronc to prevent Tau cleavage, and that the circadian clock defects
      confer sensitivity to expression of activated Dronc in response to prolonged
      light. They establish a link between the circadian clock factors, light, cell
      death pathways and Tau toxicity, potentially via dysregulation of circadian
      neuronal remodeling in the optic lobes. 

PMID- 25951231
TI  - The Effect of Bad News and CEO Apology of Corporate on User Responses in Social
      Media.
AB  - While social media has become an important platform for social reputation, the
      emotional responses of users toward bad news have not been investigated
      thoroughly. We analyzed a total of 20,773 Twitter messages by 15,513 users to
      assess the influence of bad news and public apology in social media. Based on
      both computerized, quantitative sentiment analysis and in-depth qualitative
      analysis, we found that rapid public apology effectively and immediately reduced
      the level of negative sentiment, where the degree of change in sentiments
      differed by the type of interactions users engaged in. The majority of users who
      directly conversed with corporate representatives on the new media were not
      typical consumers, but experts and practitioners. We extend the existing
      cognitive model and suggest the audiences' psychological reaction model to
      describe the information processing process during and after an organizational
      crisis and response. We also discuss various measures through which companies can
      respond to a crisis properly in social media in a fashion that is different from
      conventional mass media. 

PMID- 25951230
TI  - Interleukin-15 Dendritic Cells Harness NK Cell Cytotoxic Effector Function in a
      Contact- and IL-15-Dependent Manner.
AB  - The contribution of natural killer (NK) cells to the treatment efficacy of
      dendritic cell (DC)-based cancer vaccines is being increasingly recognized. Much
      current efforts to optimize this form of immunotherapy are therefore geared
      towards harnessing the NK cell-stimulatory ability of DCs. In this study, we
      investigated whether generation of human monocyte-derived DCs with interleukin
      (IL)-15 followed by activation with a Toll-like receptor stimulus endows these
      DCs, commonly referred to as "IL-15 DCs", with the capacity to stimulate NK
      cells. In a head-to-head comparison with "IL-4 DCs" used routinely for clinical
      studies, IL-15 DCs were found to induce a more activated, cytotoxic effector
      phenotype in NK cells, in particular in the CD56bright NK cell subset. With the
      exception of GM-CSF, no significant enhancement of cytokine/chemokine secretion
      was observed following co-culture of NK cells with IL-15 DCs. IL-15 DCs, but not
      IL-4 DCs, promoted NK cell tumoricidal activity towards both NK-sensitive and NK
      resistant targets. This effect was found to require cell-to-cell contact and to
      be mediated by DC surface-bound IL-15. This study shows that DCs can express a
      membrane-bound form of IL-15 through which they enhance NK cell cytotoxic
      function. The observed lack of membrane-bound IL-15 on "gold-standard" IL-4 DCs
      and their consequent inability to effectively promote NK cell cytotoxicity may
      have important implications for the future design of DC-based cancer vaccine
      studies. 

PMID- 25951232
TI  - A randomized phase II study of erlotinib plus nab-paclitaxel versus erlotinib
      alone as second-line therapy for Chinese patients with advanced EGFR wild-type
      non-small-cell lung cancer.
AB  - Erlotinib is a standard second-line therapy for patients with advanced non-small
      cell lung cancer (NSCLC). However, its efficacy for those patients with epidermal
      growth factor receptor (EGFR) wild-type (WT) tumors is undecided. In this
      randomized phase II study, NSCLC patients with EGFR-WT tumors, who had been
      treated with platinum-based chemotherapy but still developed disease progression,
      were assigned to receive second-line treatment of erlotinib plus nab-paclitaxel
      or erlotinib alone. We found PFS and OS were significantly improved by erlotinib
      plus nab-paclitaxel. The adverse events were also well tolerable. 

PMID- 25951233
TI  - From Graphene to Carbon Nanotubes: Variation of the Electronic States and
      Nonlinear Optical Responses.
AB  - From the same piece of graphene sheet, (3, 3) and (6, 0) carbon nanotube clips
      were obtained on the basis of the different manners of rolling. The nature of the
      electronic state varies differently with different manners of rolling and is
      significantly affected by zigzag edges. The intermediate structures formed during
      the rolling process were functionalized with fluorine and oxygen atoms to
      investigate the electronic states and nonlinear optical (NLO) responses.
      Passivation of the intermediate structures with fluorine neither changes the
      nature of electronic states and nor improves the NLO responses. In constrast,
      passivation with oxygen enhances the NLO properties and changes the electronic
      states of the structures upon passivating at the open zigzag edges. 

PMID- 25951235
TI  - Inflammation in anal fistula.

PMID- 25951236
TI  - The Association between Neuroticism and Heart Rate Variability Is Not Fully
      Explained by Cardiovascular Disease and Depression.
AB  - Neuroticism is associated with cardiovascular disease, autonomic reactivity, and
      depression. Here we address the extent to which neuroticism accounts for the
      excess heart disease risk associated with depression and test whether cardiac
      autonomic tone plays a role as mediator. Subjects were derived from a nationally
      representative sample (n = 1,255: mean age 54.5, SD = 11.5). Higher neuroticism
      was associated with reduced heart rate variability equally under rest and stress.
      The baseline structural equation model revealed significant paths from
      neuroticism to heart rate variability, cardiovascular disease and depression, and
      between depression and cardiovascular disease, controlling for age, sex, height,
      weight, and BMI. Dropping both the neuroticism to heart rate variability, and
      neuroticism to heart disease paths significantly reduced the model fit (p < .001
      in each case). We conclude that neuroticism has independent associations with
      both autonomic reactivity and cardiovascular disease, over and above its
      associations with depression and other related variables. 

PMID- 25951234
TI  - Performance of Male and Female C57BL/6J Mice on Motor and Cognitive Tasks
      Commonly Used in Pre-Clinical Traumatic Brain Injury Research.
AB  - To date, clinical trials have failed to find an effective therapy for victims of
      traumatic brain injury (TBI) who live with motor, cognitive, and psychiatric
      complaints. Pre-clinical investigators are now encouraged to include male and
      female subjects in all translational research, which is of particular interest in
      the field of neurotrauma given that circulating female hormones (progesterone and
      estrogen) have been demonstrated to exert neuroprotective effects. To determine
      whether behavior of male and female C57BL6/J mice is differentially impaired by
      TBI, male and cycling female mice were injured by controlled cortical impact and
      tested for several weeks with functional assessments commonly employed in pre
      clinical research. We found that cognitive and motor impairments post-TBI, as
      measured by the Morris water maze (MWM) and rotarod, respectively, were largely
      equivalent in male and female animals. However, spatial working memory, assessed
      by the y-maze, was poorer in female mice. Female mice were generally more active,
      as evidenced by greater distance traveled in the first exposure to the open
      field, greater distance in the y-maze, and faster swimming speeds in the MWM.
      Statistical analysis showed that variability in all behavioral data was no
      greater in cycling female mice than it was in male mice. These data all suggest
      that with careful selection of tests, procedures, and measurements, both sexes
      can be included in translational TBI research without concern for effect of
      hormones on functional impairments or behavioral variability.

PMID- 25951237
TI  - Oral Articulatory Control in Childhood Apraxia of Speech.
AB  - PURPOSE: The purpose of this research was to examine spatial and temporal aspects
      of articulatory control in children with childhood apraxia of speech (CAS),
      children with speech delay characterized by an articulation/phonological
      impairment (SD), and controls with typical development (TD) during speech tasks
      that increased in word length. METHOD: The participants included 33 children (11
      CAS, 11 SD, and 11 TD) between 3 and 7 years of age. A motion capture system was
      used to track jaw, lower lip, and upper lip movement during a naming task.
      Movement duration, velocity, displacement, and variability were measured from
      accurate word productions. RESULTS: Movement variability was significantly higher
      in the children with CAS compared with participants in the SD and TD groups.
      Differences in temporal control were seen between both groups of children with
      speech impairment and the controls with TD during accurate word productions. As
      word length increased, movement duration and variability differed between the
      children with CAS and those with SD. CONCLUSIONS: These findings provide evidence
      that movement variability distinguishes children with CAS from speakers with SD.
      Kinematic differences between the participants with CAS and those with SD suggest
      that these groups respond differently to linguistic challenges.

PMID- 25951238
TI  - JARID1B Expression Plays a Critical Role in Chemoresistance and Stem Cell-Like
      Phenotype of Neuroblastoma Cells.
AB  - Neuroblastoma (NB) is a common neural crest-derived extracranial solid cancer in
      children. Among all childhood cancers, NB causes devastating loss of young lives
      as it accounts for 15% of childhood cancer mortality. Neuroblastoma, especially
      high-risk stage 4 NB with MYCN amplification has limited treatment options and
      associated with poor prognosis. This necessitates the need for novel effective
      therapeutic strategy. JARID1B, also known as KDM5B, is a histone lysine
      demethylase, identified as an oncogene in many cancer types. Clinical data
      obtained from freely-accessible databases show a negative correlation between
      JARID1B expression and survival rates. Here, we demonstrated for the first time
      the role of JARID1B in the enhancement of stem cell-like activities and drug
      resistance in NB cells. We showed that JARID1B may be overexpressed in either
      MYCN amplification (SK-N-BE(2)) or MYCN-non-amplified (SK-N-SH and SK-N-FI) cell
      lines. JARID1B expression was found enriched in tumor spheres of SK-N-BE(2) and
      SK-N-DZ. Moreover, SK-N-BE(2) spheroids were more resistant to chemotherapeutics
      as compared to parental cells. In addition, we demonstrated that JARID1B-silenced
      cells acquired a decreased propensity for tumor invasion and tumorsphere
      formation, but increased sensitivity to cisplatin treatment. Mechanistically,
      reduced JARID1B expression led to the downregulation of Notch/Jagged signaling.
      Collectively, we provided evidence that JARID1B via modulation of stemness
      related signaling is a putative novel therapeutic target for treating malignant
      NB. 

PMID- 25951239
TI  - The hematopoietic stem cell number in the peripheral blood of pediatric
      recipients correlates with the outcome after living donor liver transplantation.
AB  - It has been proposed that circulating HSCs play a role in graft survival after
      liver transplantation. The aim was to analyze the relationship between the number
      of HSCs before and after LDLT and liver function, immune biomarkers, and clinical
      outcomes in pediatric patients. We studied 15 pairs of adult healthy liver donors
      and pediatric recipients with ESLD. The CD34/CD45+ cell number was measured in
      the blood via flow cytometry, and plasma levels of immune biomarkers - via ELISA.
      CD34/CD45+ cell number in the recipients decreased within the first week after
      LDLT. The cell number before LDLT was negatively correlated with the plasma
      levels of CRP and the development of graft dysfunction in the early post
      transplant period. After LDLT, the CD34/CD45+ cell number was positively
      correlated with the pretransplant plasma level of sCD40L, a T-cell activation
      marker. In adult liver donors, the cell number did not change within the first
      week after liver resection and was lower than in pediatric recipients. The
      results suggest that in pediatric recipients, the HSC number may be associated
      with graft function and could be regarded as a potential predictor of the
      clinical outcome after LDLT. 

PMID- 25951240
TI  - Longitudinal assessment of bone growth and development in a facility-based
      population of young adults with cerebral palsy.
AB  - AIM: Osteoporosis is a significant clinical problem in persons with moderate to
      severe cerebral palsy (CP), causing fractures with minimal trauma. Over the past
      decade, most studies examining osteoporosis and CP have been cross-sectional in
      nature, focused exclusively on children and adolescents and only involving one
      evaluation of bone mineral density (BMD). The purpose of this study was to assess
      BMD in a group including adults with CP, and changes in each individual's BMD
      over a 5- to 6-year period. METHOD: The study group included 40 residents of a
      long-term care facility aged 6 to 26 years at the time of their initial
      evaluation. Twenty-one patients (52.5%) were male, 35 (88%) were white, and 38
      (95%) were in Gross Motor Function Classification System level V. BMD was
      assessed by dual-energy X-ray absorptiometry on the right and left distal femurs
      for three distinct regions of interest. RESULTS: Five residents had a fracture
      that occurred during the study period; this represented a fracture rate of 2.1%
      per year in the study group. Longitudinally, annualized change in the median BMD
      was 0.7% to 1.0% per year in the different regions of the distal femur, but
      ranged widely among the study group, with both increases and decreases in BMD.
      Increase in BMD over time was negatively correlated with age and positively
      correlated with change in weight. INTERPRETATION: Changes in BMD over time in
      profoundly involved persons with CP can range widely, which is important to
      recognize when evaluating potential interventions to improve BMD. Age and changes
      in body weight appear the most relevant factors.

PMID- 25951241
TI  - Emotionally biased cognitive processes: the weakest link predicts prospective
      changes in depressive symptom severity.
AB  - Emotional biases in attention, interpretation, and memory are predictive of
      future depressive symptoms. It remains unknown, however, how these biased
      cognitive processes interact to predict depressive symptom levels in the long
      term. In the present study, we tested the predictive value of two integrative
      approaches to model relations between multiple biased cognitive processes, namely
      the additive (i.e., cognitive processes have a cumulative effect) vs. the weakest
      link (i.e., the dominant pathogenic process is important) model. We also tested
      whether these integrative models interacted with perceived stress to predict
      prospective changes in depressive symptom severity. At Time 1, participants
      completed measures of depressive symptom severity and emotional biases in
      attention, interpretation, and memory. At Time 2, one year later, participants
      were reassessed to determine depressive symptom levels and perceived stress.
      Results revealed that the weakest link model had incremental validity over the
      additive model in predicting prospective changes in depressive symptoms, though
      both models explained a significant proportion of variance in the change in
      depressive symptoms from Time 1 to Time 2. None of the integrative models
      interacted with perceived stress to predict changes in depressive symptomatology.
      These findings suggest that the best cognitive marker of the evolution in
      depressive symptoms is the cognitive process that is dominantly biased toward
      negative material, which operates independent from experienced stress. This
      highlights the importance of considering idiographic cognitive profiles with
      multiple cognitive processes for understanding and modifying effects of cognitive
      biases in depression. 

PMID- 25951242
TI  - Glucocorticoid receptor gene methylation and HPA-axis regulation in adolescents.
      The TRAILS study.
AB  - Early life adversity and psychopathology are thought to be linked through HPA
      axis deregulation. Changes in methylation levels of stress reactivity genes such
      as the glucocorticoid receptor gene (NR3C1) can be induced by adversity. Higher
      NR3C1 methylation levels have been associated with a reduced NR3C1 expression,
      possibly leading to impaired negative feedback regulation of the HPA-axis. In
      this study we tested whether methylation levels of NR3C1 were associated with HPA
      axis regulation, operationalized as cortisol responses. In 361 adolescents (mean
      age 16.1, SD=0.6), salivary cortisol samples were collected before, during, and
      after a social stress task, from which response measures (cortisol activation and
      recovery) were calculated. Higher NR3C1 methylation levels were associated with a
      flattened cortisol recovery slope, indicating a delayed recovery time. Cortisol
      response activation was not associated with NR3C1 methylation. These results
      suggest that methylation of NR3C1 may impair negative feedback of the HPA-axis in
      adolescents. 

PMID- 25951244
TI  - Clinical evidence inputs to comparative effectiveness research could impact the
      development of novel treatments.
AB  - AIM: This study aims to analyze the impacts of a range of clinical evidence
      generation scenarios associated with comparative effectiveness research (CER) on
      pharmaceutical innovation. MATERIALS & METHODS: We used the Global Pharmaceutical
      Policy Model to project the effect of changes in pharmaceutical producer costs,
      revenues and timings on drug innovation and health for the age 55+ populations in
      the USA and Europe through year 2060 using three clinical scenarios. RESULTS:
      Changes in producer incentives from widespread CER evidence generation and use
      had varied but often large predicted impacts on simulated outcomes in 2060.
      Effect on the number of new drug introductions ranged from a 81.1% reduction to a
      45.5% increase, and the effect on population-level life expectancy ranged from a
      15.6% reduction to a 11.4% increase compared to baseline estimates. CONCLUSION:
      The uncertainty surrounding the consequences of increased clinical evidence
      generation and use on innovation calls for a carefully measured approach to CER
      implementation, balancing near-term benefits to spending and health with long
      term implications for innovation.

PMID- 25951243
TI  - The Autism Related Protein Contactin-Associated Protein-Like 2 (CNTNAP2)
      Stabilizes New Spines: An In Vivo Mouse Study.
AB  - The establishment and maintenance of neuronal circuits depends on tight
      regulation of synaptic contacts. We hypothesized that CNTNAP2, a protein
      associated with autism, would play a key role in this process. Indeed, we found
      that new dendritic spines in mice lacking CNTNAP2 were formed at normal rates,
      but failed to stabilize. Notably, rates of spine elimination were unaltered,
      suggesting a specific role for CNTNAP2 in stabilizing new synaptic circuitry. 

PMID- 25951245
TI  - Splice of life.

PMID- 25951246
TI  - Dirty money.

PMID- 25951247
TI  - Greek cash grab.

PMID- 25951248
TI  - Keep the directive that protects research animals.

PMID- 25951260
TI  - Japanese academics fear military incursion.

PMID- 25951261
TI  - Pluto mission hunts for hazards.

PMID- 25951262
TI  - Pint-sized DNA sequencer impresses first users.

PMID- 25951264
TI  - Mysterious galactic signal points LHC to dark matter.

PMID- 25951263
TI  - Reality check for fossil-fuel divestment.

PMID- 25951265
TI  - Mammoth genomes hold recipe for Arctic elephants.

PMID- 25951266
TI  - The retirement debate: A grand exit.

PMID- 25951267
TI  - Research: Africa's fight for equality.

PMID- 25951269
TI  - Correction.

PMID- 25951268
TI  - Policy: Climate advisers must maintain integrity.

PMID- 25951273
TI  - Forests: Not just timber plantations.

PMID- 25951274
TI  - Sanctions: Interim initiative for health in Iran.

PMID- 25951275
TI  - Education: Botanists still need to tell plants apart.

PMID- 25951276
TI  - Forests: See the trees and the wood.

PMID- 25951277
TI  - Water resources: Research network to track alpine water.

PMID- 25951278
TI  - Evolution: Beauty varies with the light.

PMID- 25951279
TI  - Computer science: Nanoscale connections for brain-like circuits.

PMID- 25951281
TI  - Materials chemistry: Organic polymers form fuel from water.

PMID- 25951282
TI  - An extremely young massive clump forming by gravitational collapse in a
      primordial galaxy.
AB  - When cosmic star formation history reaches a peak (at about redshift z ~ 2),
      galaxies vigorously fed by cosmic reservoirs are dominated by gas and contain
      massive star-forming clumps, which are thought to form by violent gravitational
      instabilities in highly turbulent gas-rich disks. However, a clump formation
      event has not yet been observed, and it is debated whether clumps can survive
      energetic feedback from young stars, and afterwards migrate inwards to form
      galaxy bulges. Here we report the spatially resolved spectroscopy of a bright off
      nuclear emission line region in a galaxy at z = 1.987. Although this region
      dominates star formation in the galaxy disk, its stellar continuum remains
      undetected in deep imaging, revealing an extremely young (less than ten million
      years old) massive clump, forming through the gravitational collapse of more than
      one billion solar masses of gas. Gas consumption in this young clump is more than
      tenfold faster than in the host galaxy, displaying high star-formation efficiency
      during this phase, in agreement with our hydrodynamic simulations. The frequency
      of older clumps with similar masses, coupled with our initial estimate of their
      formation rate (about 2.5 per billion years), supports long lifetimes (about 500
      million years), favouring models in which clumps survive feedback and grow the
      bulges of present-day galaxies. 

PMID- 25951283
TI  - Curtain eruptions from Enceladus' south-polar terrain.
AB  - Observations of the south pole of the Saturnian moon Enceladus revealed large
      rifts in the south-polar terrain, informally called 'tiger stripes', named
      Alexandria, Baghdad, Cairo and Damascus Sulci. These fractures have been shown to
      be the sources of the observed jets of water vapour and icy particles and to
      exhibit higher temperatures than the surrounding terrain. Subsequent observations
      have focused on obtaining close-up imaging of this region to better characterize
      these emissions. Recent work examined those newer data sets and used
      triangulation of discrete jets to produce maps of jetting activity at various
      times. Here we show that much of the eruptive activity can be explained by broad,
      curtain-like eruptions. Optical illusions in the curtain eruptions resulting from
      a combination of viewing direction and local fracture geometry produce image
      features that were probably misinterpreted previously as discrete jets. We
      present maps of the total emission along the fractures, rather than just the jet
      like component, for five times during an approximately one-year period in 2009
      and 2010. An accurate picture of the style, timing and spatial distribution of
      the south-polar eruptions is crucial to evaluating theories for the mechanism
      controlling the eruptions. 

PMID- 25951284
TI  - Training and operation of an integrated neuromorphic network based on metal-oxide
      memristors.
AB  - Despite much progress in semiconductor integrated circuit technology, the extreme
      complexity of the human cerebral cortex, with its approximately 10(14) synapses,
      makes the hardware implementation of neuromorphic networks with a comparable
      number of devices exceptionally challenging. To provide comparable complexity
      while operating much faster and with manageable power dissipation, networks based
      on circuits combining complementary metal-oxide-semiconductors (CMOSs) and
      adjustable two-terminal resistive devices (memristors) have been developed. In
      such circuits, the usual CMOS stack is augmented with one or several crossbar
      layers, with memristors at each crosspoint. There have recently been notable
      improvements in the fabrication of such memristive crossbars and their
      integration with CMOS circuits, including first demonstrations of their vertical
      integration. Separately, discrete memristors have been used as artificial
      synapses in neuromorphic networks. Very recently, such experiments have been
      extended to crossbar arrays of phase-change memristive devices. The adjustment of
      such devices, however, requires an additional transistor at each crosspoint, and
      hence these devices are much harder to scale than metal-oxide memristors, whose
      nonlinear current-voltage curves enable transistor-free operation. Here we report
      the experimental implementation of transistor-free metal-oxide memristor
      crossbars, with device variability sufficiently low to allow operation of
      integrated neural networks, in a simple network: a single-layer perceptron (an
      algorithm for linear classification). The network can be taught in situ using a
      coarse-grain variety of the delta rule algorithm to perform the perfect
      classification of 3 * 3-pixel black/white images into three classes (representing
      letters). This demonstration is an important step towards much larger and more
      complex memristive neuromorphic networks. 

PMID- 25951286
TI  - The trouble with reference rot.

PMID- 25951285
TI  - The formation and fate of internal waves in the South China Sea.
AB  - Internal gravity waves, the subsurface analogue of the familiar surface gravity
      waves that break on beaches, are ubiquitous in the ocean. Because of their strong
      vertical and horizontal currents, and the turbulent mixing caused by their
      breaking, they affect a panoply of ocean processes, such as the supply of
      nutrients for photosynthesis, sediment and pollutant transport and acoustic
      transmission; they also pose hazards for man-made structures in the ocean.
      Generated primarily by the wind and the tides, internal waves can travel
      thousands of kilometres from their sources before breaking, making it challenging
      to observe them and to include them in numerical climate models, which are
      sensitive to their effects. For over a decade, studies have targeted the South
      China Sea, where the oceans' most powerful known internal waves are generated in
      the Luzon Strait and steepen dramatically as they propagate west. Confusion has
      persisted regarding their mechanism of generation, variability and energy budget,
      however, owing to the lack of in situ data from the Luzon Strait, where extreme
      flow conditions make measurements difficult. Here we use new observations and
      numerical models to (1) show that the waves begin as sinusoidal disturbances
      rather than arising from sharp hydraulic phenomena, (2) reveal the existence of
      >200-metre-high breaking internal waves in the region of generation that give
      rise to turbulence levels >10,000 times that in the open ocean, (3) determine
      that the Kuroshio western boundary current noticeably refracts the internal wave
      field emanating from the Luzon Strait, and (4) demonstrate a factor-of-two
      agreement between modelled and observed energy fluxes, which allows us to produce
      an observationally supported energy budget of the region. Together, these
      findings give a cradle-to-grave picture of internal waves on a basin scale, which
      will support further improvements of their representation in numerical climate
      predictions. 

PMID- 25951287
TI  - 'Living figures' make their debut.

PMID- 25951289
TI  - Gamma delta T cells.

PMID- 25951290
TI  - Honoring Dr. Waun Ki Hong, a cancer pioneer and visionary: On the occasion of his
      Festschrift, August 14, 2014.

PMID- 25951292
TI  - Miniature microscopes for large-scale imaging of neuronal activity in freely
      behaving rodents.
AB  - Recording neuronal activity in behaving subjects has been instrumental in
      studying how information is represented and processed by the brain. Recent
      advances in optical imaging and bioengineering have converged to enable time
      lapse, cell-type specific recordings of neuronal activities from large neuronal
      populations in deep-brain structures of freely behaving rodents. We will
      highlight these advancements, with an emphasis on miniaturized integrated
      microscopy for large-scale imaging in freely behaving mice. This technology
      potentially enables studies that were difficult to perform using previous
      generation imaging and current electrophysiological techniques. These studies
      include longitudinal and population-level analyses of neuronal representations
      associated with different types of naturalistic behaviors and cognitive or
      emotional processes. 

PMID- 25951291
TI  - Amine Functionalization via Oxidative Photoredox Catalysis: Methodology
      Development and Complex Molecule Synthesis.
AB  - While the use of visible light to drive chemical reactivity is of high importance
      to the development of environmentally benign chemical transformations, the
      concomitant use of a stoichiometric electron donor or acceptor is often required
      to steer the desired redox behavior of these systems. The low-cost and ubiquity
      of tertiary amine bases has led to their widespread use as reductive additives in
      photoredox catalysis. Early use of trialkylamines in this context was focused on
      their role as reductive excited state quenchers of the photocatalyst, which in
      turn provides a more highly reducing catalytic intermediate. In this Account, we
      discuss some of the observations and thought processes that have led from our use
      of amines as reductive additives to their use as complex substrates and
      intermediates for natural product synthesis. Early attempts by our group to
      construct key carbon-carbon bonds via free-radical intermediates led to the
      observation that some trialkylamines readily behave as efficient hydrogen atom
      donors under redox-active photochemical conditions. In the wake of in-depth
      mechanistic studies published in the 1970s, 1980s and 1990s, this understanding
      has in turn allowed for a systematic approach to the design of a number of
      photochemical methodologies through rational tuning of the amine component.
      Minimization of the C-H donicity of the amine additive was found to promote
      desired C-C bond formation in a number of contexts, and subsequent elucidation of
      the amine's redox fate has sparked a reevaluation of the amine's role from that
      of reagent to that of substrate. The reactivity of tertiary amines in these
      photochemical systems is complex, and allows for a number of mechanistic
      possibilities that are not necessarily mutually exclusive. A variety of
      combinations of single-electron oxidation, C-H abstraction, deprotonation, and
      beta-scission result in the formation of reactive intermediates such as alpha
      amino radicals and iminium ions. These processes have been explored in depth in
      the photochemical literature and have resulted in a firm mechanistic grasp of the
      behavior of amine radical cations in fundamental systems. Harnessing the
      synthetic potential of these transient species represents an ongoing challenge
      for the controlled functionalization of amine substrates, because these
      mechanistic possibilities may result in undesired byproduct formation or
      substrate decomposition. The presence of tertiary amines in numerous alkaloids,
      pharmaceuticals, and agrochemicals lends credence to the potential utility of
      this chemistry in natural product synthesis, and herein we will discuss how these
      transformations might be controlled for synthetic purposes. 

PMID- 25951293
TI  - One-Session Laparoscopic Management of Combined Common Bile Duct and Gallbladder
      Stones Versus Sequential ERCP Followed by Laparoscopic Cholecystectomy.
AB  - AIM: This study aimed to evaluate the efficacy and safety of laparoscopic
      management of common bile duct (CBD) stones in a single session in comparison
      with two-session procedures including endoscopic retrograde
      cholangiopancreatography (ERCP) and laparoscopic cholecystectomy (LC). The most
      popular approach to treat CBD stones that were detected before LC is with ERCP
      followed by LC. This two-session approach has some disadvantages, which include
      spontaneous passage of stones found on magnetic resonance
      cholangiopancreatography while awaiting ERCP, the risk for CBD stone passage
      between ERCP and LC or during LC due to excessive gallbladder handling, and the
      need for multiple anesthesia sessions and hospital admissions within a short
      interval. PATIENTS AND METHODS: A prospective outcome analysis was done for 150
      patients with CBD stones treated either laparoscopically in a single session with
      either transcystic exploration (conducted in 23 cases) or CBD exploration
      (conducted in 46 cases) (Group I included 75 patients) or via two sessions using
      ERCP followed by cholecystectomy (Group II included 75 patients). RESULTS: The
      rate of CBD clearance in Group I was 94.7%, whereas it was 97% in Group II. Group
      I is superior to Group II with regard to the operative time. There were no
      significant differences between the two groups regarding conversion to the open
      procedure, hospital stay, or postoperative complications. CONCLUSIONS: The single
      session laparoscopic management of CBD stones is as safe and effective as the
      gold standard sequential ERCP followed by LC with nearly the same rate of
      success, hospital stay, and complications.

PMID- 25951295
TI  - Toward Understanding of the Lower Rim Binding Preferences of Calix[4]arene.
AB  - Calixarenes form polymetallic clusters with many first row transition metals and
      lanthanides via binding at the lower rim. A detailed theoretical study of the
      relative binding preferences for calix[4]arene (C[4]) toward the first row
      transition metals is presented. In order to do this, the binding energies of C[4]
      with transition metals displaying a range of common oxidation states, and a
      variety of potential spin states of the bound cations were investigated using
      density functional theory. A known diagnostic test, B1, is employed as a measure
      to gauge the multireference nature of each compound and is used as justification
      for the choice of different DFT functionals employed.

PMID- 25951294
TI  - N-(1'-naphthyl)-3,4,5-trimethoxybenzohydrazide as microtubule destabilizer:
      Synthesis, cytotoxicity, inhibition of cell migration and in vivo activity
      against acute lymphoblastic leukemia.
AB  - Tubulin-interacting agents, like vinca alkaloid and taxanes, play a fundamental
      role in cancer chemotherapy, making cellular microtubules (MT), one of the few
      validated anticancer targets. Cancer resistance to classical MT inhibitors has
      motivated the development of novel molecules with increased efficacy and lower
      toxicity. Aiming at designing structurally-simple inhibitors of MT assembly, we
      synthesized a series of thirty-one 3,4,5-trimethoxy-hydrazones and twenty-five
      derivatives or analogs. Docking simulations suggested that a representative N
      acylhydrazone could adopt an appropriate stereochemistry inside the colchicine
      binding domain of tubulin. Several of these compounds showed anti-leukemia
      effects in the nanomolar concentration range. Interference with MT polymerization
      was validated by the compounds' ability to inhibit MT assembly at the biochemical
      and cellular level. Selective toxicity investigations done with the most potent
      compound, a 3,4,5-trimethoxy-hydrazone with a 1-naphthyl group, showed remarkably
      selective toxicity against leukemia cells in comparison with stimulated normal
      lymphocytes, and no acute toxicity in vivo. Finally, this molecule was as active
      as vincristine in a murine model of human acute lymphoblastic leukemia at a
      weekly dose of 1 mg/kg.

PMID- 25951296
TI  - Phenothiazine decorated carbazoles: effect of substitution pattern on the optical
      and electroluminescent characteristics.
AB  - A series of thienylphenothiazine decorated carbazoles were synthesized and
      characterized by optical, electrochemical, thermal, and theoretical
      investigations. Absorption spectra of the compounds are influenced by the
      substitution pattern and chromophore number density. Compounds containing 2,7
      substitution exhibited red-shifted absorption, while the chromophore loading on
      the other positions led to the increment in molar extinction coefficients due to
      the increase in the chromophore density. Multiple substitutions resulted in
      twisting of chromophores and affected the conjugative delocalization of the pi
      electrons, which produced shorter wavelength absorption for the 2,3,6,7
      tetrasubstituted derivative. Interestingly, the compounds exhibited excited-state
      solvatochromism attributable to the structural reorganization-induced electronic
      perturbations. The solvatochromic data are supportive of a general solvent
      effect, which is further confirmed by Lippert-Mataga correlation. End-capping
      with butterfly shaped phenothiazine restrained the formation of molecular
      aggregates in the solid state. All of the compounds displayed exceptional thermal
      stability attributable to the rigid carbazole building block. Solution processed
      OLED fabricated using the new materials as emitting dopants in 4,4'-bis(9H
      carbazol-9-yl)biphenyl host exhibited bluish green electroluminescence. 

PMID- 25951299
TI  - Photoinduced morphological transformations of soft nanotubes.
AB  - In water, synthetic amphiphiles composed of a photoresponsive azobenzene moiety
      and an oligoglycine hydrogen-bonding moiety selectively self-assembled into
      nanotubes with solid bilayer membranes. The nanotubes underwent morphological
      transformations induced by photoisomerization of the azobenzene moiety within the
      membranes, and the nature of the transformation depended on the number of glycine
      residues in the oligoglycine moiety (i.e., on the strength of intermolecular
      hydrogen bonding). Upon UV-light irradiation of nanotubes prepared from
      amphiphiles with the diglycine residue, trans-to-cis isomerization induced a
      transformation from nanotubes (inner diameter (i.d.) 7 nm), several hundreds of
      nanometers to several tens of micrometers in length, to imperfect nanorings (i.d.
      21-38 nm). The cis-to-trans isomerization induced by continuous visible-light
      irradiation resulted in the stacking of the imperfect nanorings to form nanotubes
      with an i.d. of 25 nm and an average length of 310 nm, which were never formed by
      a self-assembly process. Time-lapse fluorescence microscopy enabled us to
      visualize the transformation of nanotubes with an i.d. of 20 nm (self-assembled
      from amphiphiles with the monoglycine residue) to cylindrical nanofibers with an
      i.d. of 1 nm; shrinkage of the hollow cylinders started at the two open ends with
      simultaneous elongation in the direction of the long axis. 

PMID- 25951298
TI  - Inhibition of the lymphocyte metabolic switch by the oxidative burst of human
      neutrophils.
AB  - Activation of the phagocytic NADPH oxidase-2 (NOX-2) in neutrophils is a critical
      process in the innate immune system and is associated with elevated local
      concentrations of superoxide, hydrogen peroxide (H2O2) and hypochlorous acid.
      Under pathological conditions, NOX-2 activity has been implicated in the
      development of autoimmunity, indicating a role in modulating lymphocyte effector
      function. Notably, T-cell clonal expansion and subsequent cytokine production
      requires a metabolic switch from mitochondrial respiration to aerobic glycolysis.
      Previous studies demonstrate that H2O2 generated from activated neutrophils
      suppresses lymphocyte activation but the mechanism is unknown. We hypothesized
      that activated neutrophils would prevent the metabolic switch and suppress the
      effector functions of T-cells through a H2O2-dependent mechanism. To test this,
      we developed a model co-culture system using freshly isolated neutrophils and
      lymphocytes from healthy human donors. Extracellular flux analysis was used to
      assess mitochondrial and glycolytic activity and FACS analysis to assess immune
      function. The neutrophil oxidative burst significantly inhibited the induction of
      lymphocyte aerobic glycolysis, caused inhibition of oxidative phosphorylation and
      suppressed lymphocyte activation through a H2O2-dependent mechanism. Hydrogen
      peroxide and a redox cycling agent, DMNQ, were used to confirm the impact of H2O2
      on lymphocyte bioenergetics. In summary, we have shown that the lymphocyte
      metabolic switch from mitochondrial respiration to glycolysis is prevented by the
      oxidative burst of neutrophils. This direct inhibition of the metabolic switch is
      then a likely mechanism underlying the neutrophil-dependent suppression of T-cell
      effector function. 

PMID- 25951297
TI  - Arterial Hypertension Is Characterized by Imbalance of Pro-Angiogenic versus Anti
      Angiogenic Factors.
AB  - OBJECTIVE: Hypertension is the most common cardiovascular disease and the main
      risk factor for stroke, peripheral arterial disease, arterial aneurysms and
      kidney disease. It has been reported recently that hypertensive patients and
      animals are characterized by decreased density of arterioles and capillaries in
      the tissues, called rarefaction. Rarefaction significantly increases peripheral
      resistance which results in elevated blood pressure, leads to vessel damage and
      induction of inflammation. Therefore, we hypothesized that hypertension is
      associated with decreased serum concentration of physiological pro-angiogenic
      factors and concomitant increased production of angiogenesis inhibitors.
      MATERIALS AND METHODS: 82 patients diagnosed with hypertension and 34 healthy
      volunteers were recruited to the study. Flow cytometry and enzyme-linked
      immunosorbent assay (ELISA) techniques were used to measure serum levels of the
      following cytokines: endostatin, vascular endothelial growth factor (VEGF),
      interleukin 8 (IL-8), angiogenin, and basic fibroblast growth factor (bFGF).
      RESULTS: Hypertensive patients were characterized by increased serum
      concentration of endostatin which is an anti-angiogenic factor. In addition,
      hypertension was associated with decreased levels of physiological pro-angiogenic
      mediators such as: angiogenin and bFGF. The hypertensive group was also
      characterized by elevated levels of CRP, VEGF and IL-8 that are the hallmarks of
      inflammation. CONCLUSIONS: Presented results show that hypertension is
      characterized by imbalance of pro-angiogenic and anti-angiogenic factors in the
      background of inflammation.

PMID- 25951300
TI  - Sniffin' Sticks and olfactory system imaging in patients with Kallmann syndrome.
AB  - BACKGROUND: The relationship between olfactory function, rhinencephalon and
      forebrain changes in Kallmann syndrome (KS) have not been adequately
      investigated. We evaluated a large cohort of male KS patients using Sniffin'
      Sticks and MRI in order to study olfactory bulb (OB) volume, olfactory sulcus
      (OS) depth, cortical thickness close to the OS, and olfactory phenotype. METHODS:
      Olfaction was assessed administering Sniffin' Sticks(r), in 38 KS patients and 17
      controls (by means of Screening 12 test(r)). All subjects underwent magnetic
      resonance imaging (MRI) to study OB volume, sulcus depth, and cortical thickness.
      RESULTS: Compared to controls, KS patients showed smaller OB volume (p<0.0001),
      reduced sulcus depth (p<0.0001), and thicker cortex in the region close to the OS
      (p<0.0001). Anosmic KS patients had smaller OB than controls and hyposmic KS
      patients; there was no difference between hyposmic KS patients and controls. OB
      volume correlated with Sniffin' Sticks score (r = 0.64; p < 0.001), OS depth
      (p<0.0001) and, inversely, with cortical thickness changes (p<0.0001). Sniffin'
      Sticks showed an inverse correlation with cortical thickness (r = -0.5; p<0.0001)
      and a trend toward a statistically significant correlation with OS depth.
      CONCLUSION: The present study provides further evidence of the strict
      relationship between olfaction and OB volume. The strong correlation between OB
      volume and the overlying cortical changes highlights the key role of
      rhinencephalon in forebrain embryogenesis.

PMID- 25951301
TI  - Rho-kinase inhibitor Y-27632 increases cellular proliferation and migration in
      human foreskin fibroblast cells.
AB  - The idea of direct differentiation of somatic cells into other differentiated
      cell types has attracted a great interest recently. Rho-kinase inhibitor Y-27632
      (ROCKi) is a potential drug molecule, which has been reported to support the gene
      expressions typical for the chondrocytes, thus restricting their phenotypic
      conversion to fibroblastic cells upon the cellular expansion. In this study, we
      have investigated the short-term biological responses of ROCKi to human primary
      foreskin fibroblasts. The fibroblast cells were exposed to 1 and 10 MUM ROCKi
      treatments. A proteomics analysis revealed expression changes of 56 proteins, and
      a further protein pathway analysis suggested their association with the cell
      morphology, the organization, and the increased cellular movement and the
      proliferation. These functional responses were confirmed by a Cell-IQ time-lapse
      imaging analysis. Rho-kinase inhibitor treatment increased the cellular
      proliferation up to twofold during the first 12 h, and a wound model based
      migration assay showed 50% faster filling of the mechanically generated wound
      area. Additionally, significantly less vinculin-associated focal adhesions were
      present in the ROCKi-treated cells. Despite the marked changes in the cell
      behavior, ROCKi was not able to induce the expression of the chondrocyte-specific
      genes, such as procollagen alpha1 (II) and aggrecan. 

PMID- 25951302
TI  - Potent, Metabolically Stable 2-Alkyl-8-(2H-1,2,3-triazol-2-yl)-9H-adenines as
      Adenosine A2A Receptor Ligands.
AB  - Inhibition of adenosine A2A receptors has been shown to elicit a therapeutic
      response in preclinical animal models of Parkinson's disease (PD). We previously
      identified the triazolo-9H-purine, ST1535, as a potent A(2A)R antagonist. Studies
      revealed that ST1535 is extensively hydroxylated at the omega-1 position of the
      butyl side chain. Here, we describe the synthesis and evaluation of derivatives
      in which the omega-1 position has been substituted (F, Me, OH) in order to block
      metabolism. The stability of the compounds was evaluated in human liver
      microsomes (HLM), and the affinity for A(2A)R was determined. Two compounds, (2
      (3,3-dimethylbutyl)-9-methyl-8-(2H-1,2,3-triazol-2-yl)-9H-purin-6-amine (3 b) and
      4-(6-amino-9-methyl-8-(2H-1,2,3-triazol-2-yl)-9H-purin-2-yl)-2-methylbutan-2-ol
      (3 c), exhibited good affinity against A(2A)R (Ki =0.4 nM and 2 nM, respectively)
      and high in vitro metabolic stability (89.5% and 95.3% recovery, respectively,
      after incubation with HLM for two hours).

PMID- 25951304
TI  - Time-Resolved Luminescence Nanothermometry with Nitrogen-Vacancy Centers in
      Nanodiamonds.
AB  - Measuring temperature in nanoscale spatial resolution either at or far from
      equilibrium is of importance in many scientific and technological applications.
      Although negatively charged nitrogen-vacancy (NV(-)) centers in diamond have
      recently emerged as a promising nanometric temperature sensor, the technique has
      been applied only under steady state conditions so far. Here, we present a three
      point sampling method that allows real-time monitoring of the temperature changes
      over +/-100 K and a pump-probe-type experiment that enables the study of
      nanoscale heat transfer with a temporal resolution of better than 10 MUs. The
      utility of the time-resolved luminescence nanothermometry was demonstrated with
      100 nm fluorescent nanodiamonds spin-coated on a glass substrate and submerged in
      gold nanorod solution heated by a near-infrared laser, and the validity of the
      measurements was verified with finite-element numerical simulations. The combined
      theoretical and experimental approaches will be useful to implement time-resolved
      temperature sensing in laser processing of materials and even for devices in
      operation at the nanometer scale. 

PMID- 25951303
TI  - Myoblast cytonemes mediate Wg signaling from the wing imaginal disc and Delta
      Notch signaling to the air sac primordium.
AB  - The flight muscles, dorsal air sacs, wing blades, and thoracic cuticle of the
      Drosophila adult function in concert, and their progenitor cells develop together
      in the wing imaginal disc. The wing disc orchestrates dorsal air sac development
      by producing decapentaplegic and fibroblast growth factor that travel via
      specific cytonemes in order to signal to the air sac primordium (ASP). Here, we
      report that cytonemes also link flight muscle progenitors (myoblasts) to disc
      cells and to the ASP, enabling myoblasts to relay signaling between the disc and
      the ASP. Frizzled (Fz)-containing myoblast cytonemes take up Wingless (Wg) from
      the disc, and Delta (Dl)-containing myoblast cytonemes contribute to Notch
      activation in the ASP. Wg signaling negatively regulates Dl expression in the
      myoblasts. These results reveal an essential role for cytonemes in Wg and Notch
      signaling and for a signal relay system in the myoblasts. 

PMID- 25951305
TI  - Pediatric Dental Patients are Part of a Larger Picture: Detailing Population
      Realities.
AB  - The traditional setting of a dental practice may offer pediatric dentists a
      potentially isolated picture of the general health and use of health services by
      youngsters in their community. Results from the latest National Health Interview
      Survey are reviewed to provide broad dimensions to supplement and reinforce the
      general and specific information usually developed regarding individual patients.

PMID- 25951306
TI  - Biomarkers in the dentin-pulp complex: role in health and disease.
AB  - Biomarkers are functional elements at the cellular or molecular level, playing
      important roles in health and disease. The dentin-pulp complex of the tooth
      houses several biomarkers at different stages of development, and a lack of these
      biomarkers results in developmental disorders. Furthermore, biomarkers play a
      very important role in the pathogenesis of dental caries, pulpal and periapical
      pathoses in two ways - they are essential elements in the pathological process
      and their detection helps in accurate diagnosis of the pathological condition.
      The aim of this paper is to review the literature regarding the important
      biomarkers involved in the development of the dentin-pulp complex and in the
      pathological conditions involving the dentin-pulp complex. 

PMID- 25951307
TI  - Reduction in Bacterial Loading Using MTAD as an Irrigant in Pulpectomized Primary
      Teeth.
AB  - OBJECTIVE: The aim of the present study was to evaluate the reduction in
      bacterial loading uing MTAD as an irrigating solution in pulpectomized primary
      teeth. STUDY DESIGN: A randomized, controlled clinical trial was performed that
      included primary teeth with pulp necrosis. Sixty necrotic canals were included,
      30 irrigated with MTAD (experimental group) and 30 with 1% Na0Cl solution
      (control group); in all cases, 2 microbiological samples from within the canals
      were taken with sterile paper points, the first after the canal opening and
      before the first irrigation, and the second after instrumentation and final
      irrigation, before obturation. All samples were evaluated by Agar plate method.
      RESULTS: The results were statistically analyzed by student 't' test. After
      analyzing samples before and after irrigation in the control group (NaOCl), we
      found a significant decrease of bacterial load ( p = < 0.001). The same occurred
      in the MTAD group samples ( p = < 0.001). When both groups were compared post
      irrigation, a statistically significant difference was observed in favor of MTAD.
      CONCLUSION: MTAD can be suggested as an alternative irrigant for pulpectomy of
      necrotic teeth.

PMID- 25951308
TI  - A comparative clinical study of three fissure sealants on primary teeth: 24-month
      results.
AB  - AIM: The purpose of this study was to evaluate the clinical success of three
      fissure sealants(FSs) with different contents on primary teeth. STUDY DESIGN:
      Three FSs were used to seal 150 primary molars in 75 children aged 4-7 years. All
      FSs were placed on occlusal surfaces in a split-mouth and randomized clinical
      trial. For patients in Group1,amorphous calcium phosphate(ACP) containing resin
      based sealant(RBS)(Aegis) was applied to a primary molar tooth on one side ,and
      non-fluoride RBS(Helioseal) FS was applied to symmetrical molar tooth. For
      patients in Group2, fluoride-containing RBS(Helioseal F) was applied to a primary
      molar tooth on one side, and Helioseal FS was applied to symmetrical molar tooth.
      For patients in Group3,Helioseal FS was applied to a primary molar tooth on one
      side, and Aegis FS was applied to symmetrical molar tooth. Clinical evaluation of
      FSs was carried out to assess retention, marginal discoloration, marginal
      adaptation,and the presence of caries in months 1,3,6,12,18 and 24 after FS
      application. RESULTS: There were no significant differences for all criteria in
      groups 2 and 3(p?0.05). In group 1,cumulative success rates according to 24
      months' follow-up were statistically insignificant during the comparisons
      performed in terms of retention, marginal adaptation, and presence of
      caries(p?0.05). Marginal discoloration was found to be statistically
      significant(p<0.05). CONCLUSION: RBS containing ACP or fluoride may be more
      effective than conventional RBS for caries prevention.

PMID- 25951309
TI  - Giving a second thought to brisement force - a case report.
AB  - Fractures of temporomandibular joint (TMJ) may be caused by indirect trauma where
      force of trauma is transmitted to the mandibular condyle from a blow elsewhere or
      in other situations may also result from direct trauma. TMJ trauma in children is
      usually accompanied with pain, swelling, limited jaw movement and other
      additional findings. This report highlights a case of post traumatic trismus
      successfully managed with Brisement force - gradual tractional forces applied to
      the temporomandibular joint. 

PMID- 25951310
TI  - Effects of Open and Closed Endotracheal Suctioning on Intracranial Pressure and
      Cerebral Perfusion Pressure in Adult Patients With Severe Brain Injury: A
      Literature Review.
AB  - In neurologically impaired adult patients, endotracheal suctioning is a
      potentially dangerous nursing procedure because it can increase intracranial
      pressure (ICP) and decrease cerebral perfusion pressure (CPP). This article
      presents an overview of the literature relating to the appropriate techniques
      (open system suctioning and closed system suctioning) for minimizing variability
      in ICP and CPP. The research used databases such as Medline, CINAHL, Embase,
      Scopus, Cochrane Library, and TripDataBase. Literature published from January 1,
      2002, to August 31, 2013, that involved adult patients was reviewed. The main
      search strings were obtained using the following keyword combinations: "suction
      AND intracranial pressure AND cerebrovascular circulation," "brain injuries OR
      craniocerebral trauma AND suction," and "brain injuries OR craniocerebral trauma
      AND suction AND intracranial pressure." Fourteen articles were included: two
      systematic reviews, two prospective nonrandomized studies, two prospective double
      blind clinical trials, a crossover single-blind clinical trial, three prospective
      interventionist case studies, a case-control study, and three observational
      studies. Although most of the articles show an increased ICP above 20 mm Hg when
      using open system suctioning (as opposed to closed system suctioning), it is
      still not clear which technique is best for maintaining CPP. Therefore, further
      studies are needed to determine the best technique for nursing practice. 

PMID- 25951311
TI  - A Systematic Review of the Effects of Body Temperature on Outcome After Adult
      Traumatic Brain Injury.
AB  - OBJECTIVE: This systematic review describes effects of body temperature
      alterations defined as fever, controlled normothermia, and spontaneous or induced
      hypothermia on outcome after traumatic brain injury (TBI) in adults. DATA
      SOURCES: A search was conducted using PubMed, Cochrane Library database,
      Cumulative Index to Nursing and Allied Health Literature, EMBASE, and ISI Web of
      Science in July 2013 with no back date restriction except for induced hypothermia
      (2009). STUDY SELECTION: Of 1366 titles identified, 712 were reviewed. Sixteen
      articles met inclusion criteria: randomized controlled trials in hypothermia
      since 2009 (last Cochrane review) or cohort studies of temperature in TBI,
      measure core and/or brain temperature, neurologic outcome reporting, primarily
      adult patients, and English language publications. Exclusion criteria were as
      follows: most patients with non-TBI diagnosis, primarily pediatric patients, case
      reports, or laboratory/animal studies. DATA SYNTHESIS: Most studies found that
      fever avoidance resulted in positive outcomes including decreased length of stay
      in the intensive care unit; mortality; and incidence of hypertension, elevated
      intracranial pressure, and tachycardia. Hypothermia on admission correlated with
      poor outcomes. Controlled normothermia improved surrogate outcomes. Prophylactic
      induced hypothermia is not supported by the available evidence from randomized
      controlled trial. CONCLUSION: Setting a goal of normothermia, avoiding fever, and
      aggressively treating fever may be most important after TBI. Further research is
      needed to characterize the magnitude and duration of temperature alteration after
      TBI, determine if temperature alteration influences or predicts neurologic
      outcome, determine if rate of temperature change influences or predicts
      neurologic outcome, and compare controlled normothermia versus standard practice
      or hypothermia.

PMID- 25951312
TI  - A Two-Component DNA-Prime/Protein-Boost Vaccination Strategy for Eliciting Long
      Term, Protective T Cell Immunity against Trypanosoma cruzi.
AB  - In this study, we evaluated the long-term efficacy of a two-component subunit
      vaccine against Trypanosoma cruzi infection. C57BL/6 mice were immunized with
      TcG2/TcG4 vaccine delivered by a DNA-prime/Protein-boost (D/P) approach and
      challenged with T. cruzi at 120 or 180 days post-vaccination (dpv). We examined
      whether vaccine-primed T cell immunity was capable of rapid expansion and
      intercepting the infecting T. cruzi. Our data showed that D/P vaccine elicited
      CD4+ (30-38%) and CD8+ (22-42%) T cells maintained an effector phenotype up to
      180 dpv, and were capable of responding to antigenic stimulus or challenge
      infection by a rapid expansion (CD8>CD4) with type 1 cytokine (IFNgamma+ and
      TFNalpha+) production and cytolytic T lymphocyte (CTL) activity. Subsequently,
      challenge infection at 120 or 180 dpv, resulted in 2-3-fold lower parasite burden
      in vaccinated mice than was noted in unvaccinated/infected mice. Co-delivery of
      IL-12- and GMCSF-encoding expression plasmids provided no significant benefits in
      enhancing the anti-parasite efficacy of the vaccine-induced T cell immunity.
      Booster immunization (bi) with recombinant TcG2/TcG4 proteins 3-months after
      primary vaccine enhanced the protective efficacy, evidenced by an enhanced
      expansion (1.2-2.8-fold increase) of parasite-specific, type 1 CD4+ and CD8+ T
      cells and a potent CTL response capable of providing significantly improved (3
      4.5-fold) control of infecting T. cruzi. Further, CD8+T cells in vaccinated/bi
      mice were predominantly of central memory phenotype, and capable of responding to
      challenge infection 4-6-months post bi by a rapid expansion to a poly-functional
      effector phenotype, and providing a 1.5-2.3-fold reduction in tissue parasite
      replication. We conclude that the TcG2/TcG4 D/P vaccine provided long-term anti
      T. cruzi T cell immunity, and bi would be an effective strategy to maintain or
      enhance the vaccine-induced protective immunity against T. cruzi infection and
      Chagas disease. 

PMID- 25951313
TI  - Angiogenesis in The Ovary - The Most Important Regulatory Event for Follicle and
      Corpus Luteum Development and Function in Cow - An Overview.
AB  - In the ovary, the development of new capillaries from pre-existing ones
      (angiogenesis) is a complex event regulated by numerous local factors. The
      dominant regulators of angiogenesis in ovarian follicles and corpora lutea are
      the vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF),
      insulin-like growth factor (IGF), angiopoietin (ANPT) and hypoxia-inducible
      factor (HIF) family members. Antral follicles in our study were classified
      according to the oestradiol-17-beta (E2) content in follicular fluid (FF) and
      were divided into five classes (E2 < 0.5, 0.5-5, 5-20, 20-180 and >180 ng/ml FF).
      The corresponding sizes of follicles were 5-7, 8-10, 10-13, 12-14 and >14 mm,
      respectively. Follicle tissue was separated in theca interna (TI) and granulosa
      cells (GC). The corpora lutea (CL) in our study were assigned to the following
      stages: days 1-2, 3-4, 5-7, 8-12 13-16 and >18 of the oestrous cycle and months 1
      2, 3-4, 6-7 and >8 of pregnancy. The dominant regulators were measured at mRNA
      and protein expression levels; mRNA was quantified by RT-qPCR, hormone
      concentrations by RIA or EIA and their localization by immunohistochemistry. The
      highest expression for VEGF-A, FGF-2, IGF-1 and IGF-2, ANPT-2/ANPT-1 and HIF-1
      alpha was found during final follicle maturation and in CL during the early
      luteal phase (days 1-4) followed by a lower plateau afterwards. The results
      suggest the importance of these factors for angiogenesis and maintenance of
      capillary structures for final follicle maturation, CL development and function.

PMID- 25951315
TI  - Community-Acquired Pneumonia: Pathogenesis of Acute Cardiac Events and Potential
      Adjunctive Therapies.
AB  - Despite advances in antimicrobial chemotherapy and access to sophisticated
      intensive care facilities, bacterial community-acquired pneumonia (CAP) continues
      to carry an unacceptably high mortality rate of 10% to 15% in hospitalized cases.
      CAP, considered by many to be the most underestimated disease worldwide, poses a
      particular threat to the elderly whose numbers are steadily increasing in
      developed countries. Indeed, elderly patients with severe CAP, as well as those
      with other risk factors, are at significant risk for development of inflammation
      mediated acute cardiac events that may undermine the success of antimicrobial
      therapy. Adjunctive antiinflammatory strategies are, therefore, of considerable
      potential benefit in this setting. Currently, the most promising of these are the
      macrolides, corticosteroids, and, more recently, statins, all of which target
      immune/inflammatory cells. In addition, recent insights into the
      immunopathogenesis of acute coronary events in patients with CAP have revealed a
      probable pivotal role of platelet activation, potentially modifiable by agents
      that possess antiinflammatory or platelet-targeted activities or both. Statins,
      which not only possess antiinflammatory activity but also appear to target
      several pathways involved in platelet activation, seem particularly well suited
      as adjuncts to antibiotic therapy in bacterial CAP. Following a brief
      consideration of the immunopathogenesis of bacterial CAP, this review is focused
      on mechanisms of platelet activation by CAP pathogens, as well as the
      pharmacologic control thereof, with emphasis on statins. 

PMID- 25951316
TI  - Hydration of hydroxyl and amino groups examined by molecular dynamics and neutron
      scattering.
AB  - Neutron diffraction with isotopic substitution was performed on aqueous solutions
      of isopropyl alcohol and isopropylamine. The difference between these two
      measurements primarily contains information about the different hydration of the
      alcohol and amino group. This data is used as a test of the accuracy of molecular
      dynamic simulations of the same systems. Having established the level of accuracy
      of the modeling, it is employed as an interpretive tool for the experimental
      data. Even though the alcohol and the amine possess comparable hydrogen bonding
      capabilities, consisting respectively of either two hydrogen bond acceptors and
      one donor, or two hydrogen bond donors and one acceptor, we find significant
      differences in the hydration of the hydroxyl and amino groups. 

PMID- 25951314
TI  - Effects of zinc transporters on Cryptococcus gattii virulence.
AB  - Zinc is an essential nutrient for all living organisms because it is a co-factor
      of several important proteins. Furthermore, zinc may play an essential role in
      the infectiousness of microorganisms. Previously, we determined that functional
      zinc metabolism is associated with Cryptococcus gattii virulence. Here, we
      characterized the ZIP zinc transporters in this human pathogen. Transcriptional
      profiling revealed that zinc levels regulated the expression of the ZIP1, ZIP2
      and ZIP3 genes, although only the C. gattii zinc transporter Zip1 was required
      for yeast growth under zinc-limiting conditions. To associate zinc uptake defects
      with virulence, the most studied cryptococcal virulence factors (i.e., capsule,
      melanin and growth at 37  degrees C) were assessed in ZIP mutant strains;
      however, no differences were detected in these classical virulence-associated
      traits among the mutant and WT strains. Interestingly, higher levels of reactive
      oxygen species were detected in the zip1Delta and in the zip1Delta zip2Delta
      double mutants. In line with these phenotypic alterations, the zip1Delta
      zip2Delta double mutant displayed attenuated virulence in a murine model of
      cryptococcosis. Together, these results indicate that adequate zinc uptake is
      necessary for cryptococcal fitness and virulence. 

PMID- 25951317
TI  - Molecular diagnostics of myeloproliferative neoplasms.
AB  - Since the discovery of the JAK2 V617F mutation in the majority of the
      myeloproliferative neoplasms (MPN) of polycythemia vera, essential
      thrombocythemia and primary myelofibrosis ten years ago, further MPN-specific
      mutational events, notably in JAK2 exon 12, MPL exon 10 and CALR exon 9 have been
      identified. These discoveries have been rapidly incorporated into evolving
      molecular diagnostic algorithms. Whilst many of these mutations appear to have
      prognostic implications, establishing MPN diagnosis is of immediate clinical
      importance with selection, implementation and the continual evaluation of the
      appropriate laboratory methodology to achieve this diagnosis similarly vital. The
      advantages and limitations of these approaches in identifying and quantitating
      the common MPN-associated mutations are considered herein with particular regard
      to their clinical utility. The evolution of molecular diagnostic applications and
      platforms has occurred in parallel with the discovery of MPN-associated
      mutations, and it therefore appears likely that emerging technologies such as
      next-generation sequencing and digital PCR will in the future play an increasing
      role in the molecular diagnosis of MPN. 

PMID- 25951318
TI  - Formation of a Syndiotactic Organic Polymer Inside a MOF by a [2+2] Photo
      Polymerization Reaction.
AB  - Getting suitable crystals for single-crystal X-ray crystallographic analysis
      still remains an art. Obtaining single crystals of metal-organic frameworks
      (MOFs) containing organic polymers poses even greater challenges. Here we
      demonstrate the formation of a syndiotactic organic polymer ligand inside a MOF
      by quantitative [2+2] photopolymerization reaction in a single-crystal-to-single
      crystal manner. The spacer ligands with trans,trans,trans-conformation in the
      pillared-layer MOF with guest water molecules in the channels, undergo pedal
      motion to trans,cis,trans-conformation prior to [2+2] photo-cycloaddition
      reaction and yield single crystals of MOF containing two-dimensional coordination
      polymers fused with the organic polymer ligands. We also show that the organic
      polymer in the single crystals can be depolymerized reversibly by cleaving the
      cyclobutane rings upon heating. These MOFs also show interesting photoluminescent
      properties and sensing of small organic molecules. 

PMID- 25951319
TI  - Preoperative Assessment of TERT Promoter Mutation on Thyroid Core Needle Biopsies
      Supports Diagnosis of Malignancy and Addresses Surgical Strategy.
AB  - In the last decade, several molecular markers have been proposed to improve the
      diagnosis of thyroid nodules. Among these, mutations in the telomerase reverse
      transcriptase (TERT) promoter have been correlated to malignant tumors,
      characterized by highest recurrence and decreased patients' survival. This
      suggests an important role of TERT mutational analysis in the clinical diagnosis
      and management of thyroid cancer patients. The aim of the study was to
      demonstrate the adequacy of core needle biopsy (CNB) for the preoperative
      assessment of TERT mutational status, to reach a more accurate definition of
      malignancy and a more appropriate surgical planning. Indeed, CNB is gaining
      momentum for improving diagnosis of thyroid nodules deemed inconclusive by fine
      needle aspirate (FNA). The study included 50 patients submitted to CNB due to
      inconclusive FNA report. TERT mutational status was correlated with BRAF
      mutation, definitive histology, and post-operative TNM staging of the neoplasia.
      C228T mutation of the TERT promoter was reported in 10% of the papillary
      carcinomas (PTC) series. When compared with final histology, all cases harboring
      TERT mutation resulted as locally invasive PTCs. The prevalence of TERT mutated
      cases was 17.6% among locally advanced PTCs. TERT analysis on CNB allows the
      assessment of the pathological population on paraffin sections before DNA
      isolation, minimizing the risk of false negatives due to poor sampling that
      affects FNA, and gathering aggregate information about morphology and TERT
      mutational status. Data indicating a worse outcome of the tumor might be used to
      individualize treatment decision, surgical option, and follow-up design. 

PMID- 25951320
TI  - Diabetes Mellitus-Associated Functional Hypercortisolism Impairs Sexual Function
      in Male Late-Onset Hypogonadism.
AB  - Functional hypercortisolism is generated by conditions able to chronically
      activate hypothalamic-pituitary-adrenal axis and has been proven to have a
      negative role in several complications. However, no study has evaluated the
      possible influence of diabetes mellitus-associated functional hypercortisolism on
      male hypogonadism and sexual function. We aimed to identify any association of
      hypothalamic-pituitary-adrenal axis dysregulation measures with testosterone and
      sexual function in men simultaneously affected by diabetes mellitus and late
      onset hypogonadism. Fifteen diabetes mellitus and late-onset hypogonadism
      subjects suffering from functional hypercortisolism and fifteen diabetes mellitus
      and late-onset hypogonadism subjects who were free of functional hypercortisolism
      were retrospectively reviewed. Clinical, hormonal, and sexual parameters were
      considered. Hypercortisolemic subjects showed higher values of body mass index,
      waist, and glycated hemoglobin and lower ones of testosterone compared to
      normocortisolemic ones. All sexual parameters, except for orgasmic function, were
      significantly worse in hypercortisolemic than in normocortisolemic subjects.
      Hypercortisolemic patients showed higher values of cortisol after dexamethasone
      and urinary free cortisol as well as a lesser ACTH response after corticotropin
      releasing hormone test (ACTH area under curve) compared to normocortisolemic
      ones. No significant association was found at Poisson regression analysis between
      hormonal and sexual variables in normocortisolemic patients. In hypercortisolemic
      subjects, negative and significant associations of cortisol response after
      corticotropin releasing hormone (cortisol area under curve) with erectile
      function (beta: -0.0008; p: 0.015) and total international index of erectile
      function score (beta: -0.0006; p: 0.001) were evident. This study suggests for
      the first time the impairing influence of the dysregulated hypothalamic-pituitary
      adrenal axis on sexual function in diabetes mellitus-associated late-onset
      hypogonadism. 

PMID- 25951321
TI  - The Effect of Klotho Treatment on Atherogenesis, Blood Pressure, and Metabolic
      Parameters in Experimental Rodent Models.
AB  - Klotho is a transmembrane protein, expressed mainly in the kidneys and the
      choroid plexus. The extracellular domain of klotho is composed of 2 internal
      repeats, KL1 and KL2, which can be cleaved and act as hormones. Klotho-deficient
      mice develop a phenotype resembling human aging. Laboratory and clinical data
      suggest a favorable effect of klotho on atherosclerosis, high blood pressure, and
      metabolic syndrome. Therefore, we aimed to study the effect of klotho treatment
      on atherogenesis, blood pressure, and metabolic parameters in experimental rodent
      models. Fructose-fed Sprague-Dawley rats (metabolic syndrome model) and
      apolipoprotein E (apoE -/-) knock-out mice (atherosclerosis model) were treated
      with either klotho or its active domain KL1. In apoE -/- mice, klotho
      unexpectedly elevated plasma cholesterol and triglyceride levels compared to the
      control group. Yet, it did not increase the aortic sinus atherosclerotic lesion
      area. In fructose-fed Sprague-Dawley rats, klotho treatment did not lower blood
      pressure or plasma triglyceride levels. Although KL1 treatment did not lower
      blood pressure or plasma insulin levels, it significantly reduced the elevation
      of total plasma triglyceride levels (from 2.3-fold to 1.6-fold, p<0.05) due to
      lower triglyceride-rich VLDL levels. Klotho did not show any beneficial effects
      on atherosclerosis and components of the metabolic syndrome and was associated
      with increased plasma cholesterol levels. On the other hand, treatment with KL1
      may lower plasma triglyceride levels independent of insulin. Additional studies
      are required in order to decipher the complex role of klotho and its active
      domains in the regulation of plasma lipid levels. 

PMID- 25951322
TI  - 11-Keto-beta-Boswellic Acids Prevent Development of Autoimmune Reactions,
      Insulitis and Reduce Hyperglycemia During Induction of Multiple Low-Dose
      Streptozotocin (MLD-STZ) Diabetes in Mice.
AB  - The aim of the work was to study whether or not 11-keto-beta-boswellic acids
      prevent induction of autoimmune reactions, insulitis, and hyperglycemia in the
      model of multiple low-dose streptozotocin (MLD-STZ) diabetes. Using male mice (n
      = 6) diabetes was induced by daily i.p. injections of 40 mg/kg STZ for 5 days. In
      a second series together with STZ, daily i. p. injections of 11-keto-beta
      boswellic acid (KBA) and O-acetyl-11-keto-beta-boswellic acid (AKBA) (7.5 and
      15.0 mg/kg) were applied for 10 days. Thereafter, pro-and anti-inflammatory
      cytokines in the blood, histochemistry of pancreatic islets, and blood glucose
      levels were assayed. Five days after the last injection of STZ, a significant
      burst of pro-and anti-inflammatory cytokines in the blood, infiltration of
      lymphocytes (CD3) into pancreatic islets, and appearance of peri-insular
      apoptotic cells were observed. Plasma glucose increased significantly (124.4 +/-
      6.65 vs. 240.2 +/- 27.36 mg/dl, p <0.05). Simultaneous treatment with KBA and
      AKBA significantly reduced pro-and anti-inflammatory cytokines (IFN-gamma p <
      0.01, p < 0.01; IL-1A p < 0.001, p < 0.001; IL-1B p < 0.001, p < 0.001; IL-2 p <
      0.001, p < 0.001; IL-6 p < 0.01, p < 0.001; TNF-alpha p < 0.05, p < 0.001; IL-4 p
      < 0.01, p < 0.001; IL-10 p < 0.001, p < 0.001) in the blood. No infiltration of
      lymphocytes into pancreatic islets and appearance of peri-insular cells were
      detected. Moreover, KBA and AKBA reduced STZ-mediated increase of blood glucose
      on day 10 to 163.25 +/- 16.6 (p < 0.05) and 187.6 +/- 19.5 mg/dl (p < 0.05),
      respectively. In the model of MLD-STZ induced diabetes KBA and AKBA prevent
      cytokine burst, development of insulitis and reduce increase of blood glucose
      through "silencing" a forced-up immune reaction.

PMID- 25951323
TI  - Protective Effects of Liraglutide and Linagliptin in C. elegans as a New Model
      for Glucose-Induced Neurodegeneration.
AB  - Liraglutide and linagliptin are novel drugs for the treatment of diabetes.
      Antioxidative and neuroprotective effects have been described for both compounds.
      However, it is not yet known, whether these mechanisms are also protective
      against diabetic retinal neurodegeneration. We assessed the antioxidative and
      neuroprotective capabilities of liraglutide and linagliptin as well as the
      signaling pathways involved, by using C. elegans as a model for glucose-induced
      neurodegeneration. C. elegans were cultivated under conditions, which mimic
      clinical hyperglycemia, and treated with 160 MUmol/l liraglutide or 13 MUmol/l
      linagliptin. Oxidative stress was reduced by 29 or 78% and methylglyoxal-derived
      advanced glycation endproducts (AGEs) by 33 or 22%, respectively. This resulted
      in an improved neuronal function by 42 or 60% and an extended mean lifespan by 9
      or 11%, respectively. Antioxidative and AGE reducing effects of liraglutide and
      linagliptin were not dependent on v-akt murine thymoma viral oncogene homologue
      1/forkhead box O1 (AKT1/FOXO). Neuroprotection by liraglutide was AKT1/FOXO
      dependent, yet AKT1/FOXO independent upon linagliptin treatment. Both liraglutide
      and linagliptin exert neuroprotective effects in an experimental model for
      glucose-induced neurodegeneration, however, the signaling pathways differ in the
      present study. Further pharmacological intervention with these pathways may help
      to delay the clinical onset of diabetic retinopathy by preserving neuronal
      integrity. 

PMID- 25951324
TI  - Modern Hydrocortisone Replacement Regimens in Adrenal Insufficiency Patients and
      the Risk of Adrenal Crisis.
AB  - The aim of this study was to examine the incidence of adrenal crises (AC) and the
      prescription of short-acting glucocorticoids (GC) in different geographic areas.
      To do this we conducted a descriptive study of AC hospitalisations and
      prescriptions for two GCs (hydrocortisone (HC) and cortisone acetate (CA)), and
      fludrocortisone acetate (FA), in different geographic areas of Australia between
      1999/2000 and 2011/2012, using government databases.There were 2,584 hospital
      admissions for AC in Australia between 1999/00 and 2011/12 and the corresponding
      admission rates increased significantly from 7.4 to 11.1/10(6)/year (p<0.001). AC
      admission rates increased in 5 out of 6 geographic areas. Prescription rates for
      the combined GCs (HC/CA) increased at an annual rate of between 0.2-2.0% in all
      areas. All areas had significant (p<0.01) increases in HC prescription rates
      (4.5% to 13.7% annually) and CA prescription rates decreased in 5 out of the 6
      regions (3.5% annual decrease to a 0.5% annual increase). When the geographic
      areas were combined, there was a significant correlation between the AC admission
      rates and HC/CA prescription rates (r=0.30, p<0.01). Admissions for AC and GC
      prescriptions increased significantly in Australia after 1999 and these varied
      significantly by geographic area. These results suggest that modern
      recommendations for lower dose, short-acting GC replacement may be of concern and
      further investigation is warranted.

PMID- 25951325
TI  - Design of on-chip N-fold orbital angular momentum multicasting using V-shaped
      antenna array.
AB  - We design a V-shaped antenna array to realize on-chip multicasting from a single
      Gaussian beam to four orbital angular momentum (OAM) beams. A pattern search
      assisted iterative (PSI) algorithm is used to design an optimized continuous
      phase pattern which is further discretized to generate collinearly superimposed
      multiple OAM beams. Replacing the designed discrete phase pattern with
      corresponding V-shaped antennas, on-chip N-fold OAM multicasting is achieved. The
      designed on-chip 4-fold OAM multicasting exploiting V-shaped antenna array shows
      favorable operation performance with low crosstalk less than -15 dB. 

PMID- 25951326
TI  - An Examination of the Relationship between Lipid Levels and Associated Genetic
      Markers across Racial/Ethnic Populations in the Multi-Ethnic Study of
      Atherosclerosis.
AB  - Large genome-wide association studies have reported hundreds of genetic markers
      associated with lipid levels. However, the discovery and estimated effect of
      variants at these loci, derived from samples of exclusively European descent, may
      not generalize to the majority of the world populations. We examined the
      collective strength of association among these loci in a diverse set of U.S.
      populations from the Multi-Ethnic Study of Atherosclerosis. We constructed a
      genetic risk score for each lipid outcome based on previously identified lipid
      associated genetic markers, and examined the relationship between the genetic
      risk scores and corresponding outcomes. We discover this relationship was often
      moderated by race/ethnicity. Our findings provide insight into the
      generalizability and predictive utility of large sample size meta-analyses
      results when leveraging data from a single population. We hope these findings
      will encourage researchers to investigate genetic susceptibility in more diverse
      populations and explore the source of such discrepancies. Until then, we caution
      clinicians, genetic counselors, and genetic testing consumers when interpreting
      genetic data on complex traits. 

PMID- 25951327
TI  - Correction: Community-centered responses to Ebola in urban Liberia: the view from
      below.

PMID- 25951328
TI  - Annual Carbon Emissions from Deforestation in the Amazon Basin between 2000 and
      2010.
AB  - Reducing emissions from deforestation and forest degradation (REDD+) is
      considered one of the most cost-effective strategies for mitigating climate
      change. However, historical deforestation and emission rates-critical inputs for
      setting reference emission levels for REDD+-are poorly understood. Here we use
      multi-source, time-series satellite data to quantify carbon emissions from
      deforestation in the Amazon basin on a year-to-year basis between 2000 and 2010.
      We first derive annual deforestation indicators by using the Moderate Resolution
      Imaging Spectroradiometer Vegetation Continuous Fields (MODIS VCF) product. MODIS
      indicators are calibrated by using a large sample of Landsat data to generate
      accurate deforestation rates, which are subsequently combined with a spatially
      explicit biomass dataset to calculate committed annual carbon emissions. Across
      the study area, the average deforestation and associated carbon emissions were
      estimated to be 1.59 +/- 0.25 M ha*yr(-1) and 0.18 +/- 0.07 Pg C*yr(-1)
      respectively, with substantially different trends and inter-annual variability in
      different regions. Deforestation in the Brazilian Amazon increased between 2001
      and 2004 and declined substantially afterwards, whereas deforestation in the
      Bolivian Amazon, the Colombian Amazon, and the Peruvian Amazon increased over the
      study period. The average carbon density of lost forests after 2005 was 130 Mg
      C*ha(-1), ~11% lower than the average carbon density of remaining forests in year
      2010 (144 Mg C*ha(-1)). Moreover, the average carbon density of cleared forests
      increased at a rate of 7 Mg C*ha(-1)*yr(-1) from 2005 to 2010, suggesting that
      deforestation has been progressively encroaching into high-biomass lands in the
      Amazon basin. Spatially explicit, annual deforestation and emission estimates
      like the ones derived in this study are useful for setting baselines for REDD+
      and other emission mitigation programs, and for evaluating the performance of
      such efforts.

PMID- 25951329
TI  - Males Resemble Females: Re-Evaluating Sexual Dimorphism in Protoceratops andrewsi
      (Neoceratopsia, Protoceratopsidae).
AB  - BACKGROUND: Protoceratops andrewsi (Neoceratopsia, Protoceratopsidae) is a well
      known dinosaur from the Upper Cretaceous of Mongolia. Some previous workers
      hypothesized sexual dimorphism in the cranial shape of this taxon, using
      qualitative and quantitative observations. In particular, width and height of the
      frill as well as the development of a nasal horn have been hypothesized as
      potentially sexually dimorphic. METHODOLOGY/PRINCIPAL FINDINGS: Here, we reassess
      potential sexual dimorphism in skulls of Protoceratops andrewsi by applying two
      dimensional geometric morphometrics to 29 skulls in lateral and dorsal views.
      Principal Component Analyses and nonparametric MANOVAs recover no clear
      separation between hypothetical "males" and "females" within the overall
      morphospace. Males and females thus possess similar overall cranial morphologies.
      No differences in size between "males" and "females" are recovered using
      nonparametric ANOVAs. CONCLUSIONS/SIGNIFICANCE: Sexual dimorphism within
      Protoceratops andrewsi is not strongly supported by our results, as previously
      proposed by several authors. Anatomical traits such as height and width of the
      frill, and skull size thus may not be sexually dimorphic. Based on PCA for a data
      set focusing on the rostrum and associated ANOVA results, nasal horn height is
      the only feature with potential dimorphism. As a whole, most purported dimorphic
      variation is probably primarily the result of ontogenetic cranial shape changes
      as well as intraspecific cranial variation independent of sex.

PMID- 25951330
TI  - Palmitoylethanolamide treatment reduces blood pressure in spontaneously
      hypertensive rats: involvement of cytochrome p450-derived eicosanoids and renin
      angiotensin system.
AB  - Palmitoylethanolamide (PEA), a peroxisome proliferator-activated receptor-alpha
      agonist, has been demonstrated to reduce blood pressure and kidney damage
      secondary to hypertension in spontaneously hypertensive rat (SHR). Currently, no
      information is available concerning the putative effect of PEA on modulating
      vascular tone. Here, we investigate the mechanisms underpinning PEA blood
      pressure lowering effect, exploring the contribution of epoxyeicosatrienoic
      acids, CYP-dependent arachidonic acid metabolites, as endothelium-derived
      hyperpolarizing factors (EDHF), and renin angiotensin system (RAS) modulation. To
      achieve this aim SHR and Wistar-Kyoto rats were treated with PEA (30 mg/kg/day)
      for five weeks. Functional evaluations on mesenteric bed were performed to
      analyze EDHF-mediated vasodilation. Moreover, mesenteric bed and carotid were
      harvested to measure CYP2C23 and CYP2J2, the key isoenzymes in the formation of
      epoxyeicosatrienoic acids, and the soluble epoxide hydrolase, which is
      responsible for their degradation in the corresponding diols. Effect of PEA on
      RAS modulation was investigated by analyzing angiotensin converting enzyme and
      angiotensin receptor 1 expression. Here, we showed that EDHF-mediated dilation in
      response to acetylcholine was increased in mesenteric beds of PEA-treated SHR.
      Western blot analysis revealed that the increase in CYP2C23 and CYP2J2 observed
      in SHR was significantly attenuated in mesenteric beds of PEA-treated SHR, but
      unchanged in the carotids. Interestingly, in both vascular tissues, PEA
      significantly decreased the soluble epoxide hydrolase protein level, accompanied
      by a reduced serum concentration of its metabolite 14-15 dihydroxyeicosatrienoic
      acid, implying a reduction in epoxyeicosatrienoic acid hydrolisis. Moreover, PEA
      treatment down-regulated angiotensin receptor 1 and angiotensin converting enzyme
      expression, indicating a reduction in angiotensin II-mediated effects.
      Consistently, a damping of the activation of angiotensin receptor 1 underlying
      pathways in mesenteric beds was shown in basal conditions in PEA-treated SHR. In
      conclusion, our data demonstrate the involvement of epoxyeicosatrienoic acids and
      renin angiotensin system in the blood pressure lowering effect of PEA. 

PMID- 25951332
TI  - Informative simultaneous confidence intervals for the fallback procedure.
AB  - The fallback procedure is an extension of the hierarchical test procedure
      relaxing the predefined hierarchical order. It can be applied for example in dose
      finding studies. If interest is in extending the fallback procedure to
      simultaneous confidence intervals, one finds proposals in the literature, which
      have, however, the drawback that noninformative rejections may arise. A
      noninformative rejection means that the confidence interval of a rejected null
      hypothesis contains all parameters of the alternative and thus gives no useful
      information about the true value of the effect parameter. We present a
      modification of the fallback procedure with corresponding simultaneous confidence
      intervals that is informative in every case where a hypothesis is rejected. The
      main idea consists of splitting the level between the null hypotheses and a
      nested family of informative hypotheses constituting the alternative. The
      splitting weights depend continuously on the parameter. The new method is
      represented by a simple graph and can be easily implemented by an explicit
      algorithm. We give an example and compare our approach with an existing extension
      of the fallback procedure to simultaneous confidence intervals by simulations in
      the context of a dose-finding clinical trial. As a result, we see that the
      problem of noninformative rejections can be completely removed by the informative
      fallback procedure, while the involved power loss can be controlled by careful
      planning. 

PMID- 25951333
TI  - Is the area of the orbital opening in humans related to climate?
AB  - OBJECTIVES: The aim of this study was to evaluate whether climatic conditions
      impact the size of the anterior orbital opening in humans. The previous research
      has shown that morphology of the human orbit, a trait strongly related to the
      shape of the cranium, varies significantly among populations. However, the
      mechanisms of this variation are still debatable. Besides such evolutionary
      forces as genetic drift, climatic conditions may be involved. Thermoregulatory
      processes affect skull shape, and thus may also influence orbital morphology.
      METHODS: A total of 846 dry skulls of male and female adults from three climatic
      areas (i.e., warm, temperate, and cold) of Europe were evaluated. The areas of
      the left and right orbital openings were measured using the three-dimensional
      contact scanner MicroScribe G2L, and analyzed with regard to climate. RESULTS:
      The results reveal a statistically significant association with climatic
      conditions on the area of orbital opening in accordance with Bergmann's rule. The
      anterior orbital opening area was smaller in male individuals from the cold
      climate, and larger in individuals from the warm climate areas. CONCLUSIONS:
      These data may support the hypothesized association between size of the orbital
      opening and adaptation to different climatic conditions, but only in males.

PMID- 25951334
TI  - Inductive proteomics and large dataset collections.

PMID- 25951331
TI  - Alterations in perivascular sympathetic and nitrergic innervation function
      induced by late pregnancy in rat mesenteric arteries.
AB  - BACKGROUND AND PURPOSE: We investigated whether pregnancy was associated with
      changed function in components of perivascular mesenteric innervation and the
      mechanism/s involved. EXPERIMENTAL APPROACH: We used superior mesenteric arteries
      from female Sprague-Dawley rats divided into two groups: control rats (in
      oestrous phase) and pregnant rats (20 days of pregnancy). Modifications in the
      vasoconstrictor response to electrical field stimulation (EFS) were analysed in
      the presence/absence of phentolamine (alpha-adrenoceptor antagonist) or L-NAME
      (nitric oxide synthase-NOS- non-specific inhibitor). Vasomotor responses to
      noradrenaline (NA), and to NO donor DEA-NO were studied, NA and NO release
      measured and neuronal NOS (nNOS) expression/activation analysed. KEY RESULTS: EFS
      induced a lower frequency-dependent contraction in pregnant than in control rats.
      Phentolamine decreased EFS-induced vasoconstriction in segments from both
      experimental groups, but to a greater extent in control rats. EFS-induced
      vasoconstriction was increased by L-NAME in arteries from both experimental
      groups. This increase was greater in segments from pregnant rats. Pregnancy
      decreased NA release while increasing NO release. nNOS expression was not
      modified but nNOS activation was increased by pregnancy. Pregnancy decreased NA
      induced vasoconstriction response and did not modify DEA-NO-induced vasodilation
      response. CONCLUSIONS AND IMPLICATIONS: Neural control of mesenteric vasomotor
      tone was altered by pregnancy. Diminished sympathetic and enhanced nitrergic
      components both contributed to the decreased vasoconstriction response to EFS
      during pregnancy. All these changes indicate the selective participation of
      sympathetic and nitrergic innervations in vascular adaptations produced during
      pregnancy.

PMID- 25951335
TI  - Remediation of Urban River Water by Pontederia Cordata Combined with Artificial
      Aeration: Organic Matter and Nutrients Removal and Root-Adhered Bacterial
      Communities.
AB  - Macrophyte combined with artificial aeration is a promising in situ remediation
      approach for urban rivers polluted with nutrients and organic matter. However,
      seasonal variations and aeration effects on phytoremediation performance and root
      adhered microbial communities are still unclear. In this study, Pontederia
      cordata was used to treat polluted urban river water under various aeration
      intensities. Results showed that the highest removal efficiencies of chemical
      oxygen demand (COD(Cr)) and total nitrogen (TN) were attained under aeration of
      30 L min(-1) in spring and summer and 15 L min(-1) in autumn, while total
      phosphorus (TP) removal reached maximum with aeration of 15 L min(-1) in all
      seasons. Moderate aeration was beneficial for increasing the diversity of root
      adhered bacteria communities, and the shift of bacterial community structure was
      more pronounced in spring and autumn with varying aeration intensity. The dual
      effect, i.e. turbulence and dissolved oxygen (DO), of aeration on the removal of
      COD(Cr) and TN prevailed over the individual effect of DO, while DO was the most
      influential factor for TP removal and the root-adhered bacterial community
      diversity. P. cordata combined with 15 L min(-1) aeration was deemed to be the
      best condition tested in this study.

PMID- 25951337
TI  - Enhanced sensitive love wave surface acoustic wave sensor designed for
      immunoassay formats.
AB  - We report a Love wave surface acoustic wave (LW-SAW) immunosensor designed for
      the detection of high molecular weight targets in liquid samples, amenable also
      for low molecular targets in surface competition assays. We implemented a label
      free interaction protocol similar to other surface plasmon resonance bioassays
      having the advantage of requiring reduced time analysis. The fabricated LW-SAW
      sensor supports the detection of the target in the nanomolar range, and can be
      ultimately incorporated in portable devices, suitable for point-of-care testing
      (POCT) applications. 

PMID- 25951338
TI  - A novel square-root cubature information weighted consensus filter algorithm for
      multi-target tracking in distributed camera networks.
AB  - This paper deals with the problem of multi-target tracking in a distributed
      camera network using the square-root cubature information filter (SCIF). SCIF is
      an efficient and robust nonlinear filter for multi-sensor data fusion. In camera
      networks, multiple cameras are arranged in a dispersed manner to cover a large
      area, and the target may appear in the blind area due to the limited field of
      view (FOV). Besides, each camera might receive noisy measurements. To overcome
      these problems, this paper proposes a novel multi-target square-root cubature
      information weighted consensus filter (MTSCF), which reduces the effect of
      clutter or spurious measurements using joint probabilistic data association
      (JPDA) and proper weights on the information matrix and information vector. The
      simulation results show that the proposed algorithm can efficiently track
      multiple targets in camera networks and is obviously better in terms of accuracy
      and stability than conventional multi-target tracking algorithms. 

PMID- 25951336
TI  - Surface plasmon resonance: a versatile technique for biosensor applications.
AB  - Surface plasmon resonance (SPR) is a label-free detection method which has
      emerged during the last two decades as a suitable and reliable platform in
      clinical analysis for biomolecular interactions. The technique makes it possible
      to measure interactions in real-time with high sensitivity and without the need
      of labels. This review article discusses a wide range of applications in optical
      based sensors using either surface plasmon resonance (SPR) or surface plasmon
      resonance imaging (SPRI). Here we summarize the principles, provide examples, and
      illustrate the utility of SPR and SPRI through example applications from the
      biomedical, proteomics, genomics and bioengineering fields. In addition, SPR
      signal amplification strategies and surface functionalization are covered in the
      review. 

PMID- 25951339
TI  - A novel artificial fish swarm algorithm for recalibration of fiber optic
      gyroscope error parameters.
AB  - The artificial fish swarm algorithm (AFSA) is one of the state-of-the-art swarm
      intelligent techniques, which is widely utilized for optimization purposes. Fiber
      optic gyroscope (FOG) error parameters such as scale factors, biases and
      misalignment errors are relatively unstable, especially with the environmental
      disturbances and the aging of fiber coils. These uncalibrated error parameters
      are the main reasons that the precision of FOG-based strapdown inertial
      navigation system (SINS) degraded. This research is mainly on the application of
      a novel artificial fish swarm algorithm (NAFSA) on FOG error coefficients
      recalibration/identification. First, the NAFSA avoided the demerits (e.g., lack
      of using artificial fishes' pervious experiences, lack of existing balance
      between exploration and exploitation, and high computational cost) of the
      standard AFSA during the optimization process. To solve these weak points,
      functional behaviors and the overall procedures of AFSA have been improved with
      some parameters eliminated and several supplementary parameters added. Second, a
      hybrid FOG error coefficients recalibration algorithm has been proposed based on
      NAFSA and Monte Carlo simulation (MCS) approaches. This combination leads to
      maximum utilization of the involved approaches for FOG error coefficients
      recalibration. After that, the NAFSA is verified with simulation and experiments
      and its priorities are compared with that of the conventional calibration method
      and optimal AFSA. Results demonstrate high efficiency of the NAFSA on FOG error
      coefficients recalibration. 

PMID- 25951340
TI  - Sensor node for remote monitoring of waterborne disease-causing bacteria.
AB  - A sensor node for sampling water and checking for the presence of harmful
      bacteria such as E. coli in water sources was developed in this research. A
      chromogenic enzyme substrate assay method was used to easily detect coliform
      bacteria by monitoring the color change of the sampled water mixed with a
      reagent. Live webcam image streaming to the web browser of the end user with a Wi
      Fi connected sensor node shows the water color changes in real time. The liquid
      can be manipulated on the web-based user interface, and also can be observed by
      webcam feeds. Image streaming and web console servers run on an embedded
      processor with an expansion board. The UART channel of the expansion board is
      connected to an external Arduino board and a motor driver to control self-priming
      water pumps to sample the water, mix the reagent, and remove the water sample
      after the test is completed. The sensor node can repeat water testing until the
      test reagent is depleted. The authors anticipate that the use of the sensor node
      developed in this research can decrease the cost and required labor for testing
      samples in a factory environment and checking the water quality of local water
      sources in developing countries. 

PMID- 25951341
TI  - Robust pedestrian detection by combining visible and thermal infrared cameras.
AB  - With the development of intelligent surveillance systems, the need for accurate
      detection of pedestrians by cameras has increased. However, most of the previous
      studies use a single camera system, either a visible light or thermal camera, and
      their performances are affected by various factors such as shadow, illumination
      change, occlusion, and higher background temperatures. To overcome these
      problems, we propose a new method of detecting pedestrians using a dual camera
      system that combines visible light and thermal cameras, which are robust in
      various outdoor environments such as mornings, afternoons, night and rainy days.
      Our research is novel, compared to previous works, in the following four ways:
      First, we implement the dual camera system where the axes of visible light and
      thermal cameras are parallel in the horizontal direction. We obtain a geometric
      transform matrix that represents the relationship between these two camera axes.
      Second, two background images for visible light and thermal cameras are
      adaptively updated based on the pixel difference between an input thermal and pre
      stored thermal background images. Third, by background subtraction of thermal
      image considering the temperature characteristics of background and size
      filtering with morphological operation, the candidates from whole image (CWI) in
      the thermal image is obtained. The positions of CWI (obtained by background
      subtraction and the procedures of shadow removal, morphological operation, size
      filtering, and filtering of the ratio of height to width) in the visible light
      image are projected on those in the thermal image by using the geometric
      transform matrix, and the searching regions for pedestrians are defined in the
      thermal image. Fourth, within these searching regions, the candidates from the
      searching image region (CSI) of pedestrians in the thermal image are detected.
      The final areas of pedestrians are located by combining the detected positions of
      the CWI and CSI of the thermal image based on OR operation. Experimental results
      showed that the average precision and recall of detecting pedestrians are 98.13%
      and 88.98%, respectively. 

PMID- 25951342
TI  - Tracking diurnal variation in photosynthetic down-regulation using low cost
      spectroscopic instrumentation.
AB  - Photosynthetic light-use efficiency (LUE) has gained wide interest as an input to
      modeling forest gross primary productivity (GPP). The photochemical reflectance
      index (PRI) has been identified as a principle means to inform LUE-based models,
      using airborne and satellite-based observations of canopy reflectance. More
      recently, low-cost electronics have become available with the potential to
      provide for dense in situ time-series measurements of PRI. A recent design makes
      use of interference filters to record light transmission within narrow wavebands.
      Uncertainty remains as to the dynamic range of these sensors and performance
      under low light conditions, the placement of the reference band, and methodology
      for reflectance calibration. This paper presents a low-cost sensor design and is
      tested in a laboratory set-up, as well in the field. The results demonstrate an
      excellent performance against a calibration standard (R2 = 0.9999) and at low
      light conditions. Radiance measurements over vegetation demonstrate a reversible
      reduction in green reflectance that was, however, seen in both the reference and
      signal wavebands. Time-series field measurements of PRI in a Douglas-fir canopy
      showed a weak correlation with eddy-covariance-derived LUE and a significant
      decline in PRI over the season. Effects of light quality, bidirectional
      scattering effects, and possible sensor artifacts on PRI are discussed. 

PMID- 25951343
TI  - The Influence of Parental Communication and Perception of Peers on Adolescent
      Sexual Behavior.
AB  - The authors used the theory of planned behavior to examine the influence of
      parents and peers on early adolescent sexual attitudes, self-efficacy to limit
      sexual behavior, and behavioral intentions to have vaginal intercourse.
      Adolescents (N = 212) provided self-reports of their perception of parent and
      peer attitudes regarding sexual behavior. The authors used bivariate and
      regression analyses to examine the relation between parent and peer attitudes
      with adolescent sexual attitudes, self-efficacy to limit sexual behavior, and
      behavioral intentions to have vaginal intercourse. Although there were gender
      differences, the analyses revealed the importance of both parents and peers on
      adolescent sexual attitudes, self-efficacy to limit sexual behavior, and
      intentions to have vaginal sex in the next year.

PMID- 25951344
TI  - Oceanographic Currents and Local Ecological Knowledge Indicate, and Genetics Does
      Not Refute, a Contemporary Pattern of Larval Dispersal for The Ornate Spiny
      Lobster, Panulirus ornatus in the South-East Asian Archipelago.
AB  - Here we utilize a combination of genetic data, oceanographic data, and local
      ecological knowledge to assess connectivity patterns of the ornate spiny lobster
      Panulirus ornatus (Fabricius, 1798) in the South-East Asian archipelago from
      Vietnam to Australia. Partial mitochondrial DNA control region and 10 polymorphic
      microsatellites did not detect genetic structure of 216 wild P. ornatus samples
      from Australia, Indonesia and Vietnam. Analyses show no evidence for genetic
      differentiation among populations (mtDNA control region sequences PhiST = -0.008;
      microsatellite loci FST = 0.003). A lack of evidence for regional or localized
      mtDNA haplotype clusters, or geographic clusters of microsatellite genotypes,
      reveals a pattern of high gene flow in P. ornatus throughout the South-East Asian
      Archipelago. This lack of genetic structure may be due to the oceanography-driven
      connectivity of the pelagic lobster larvae between spawning grounds in Papua New
      Guinea, the Philippines and, possibly, Indonesia. The connectivity cycle
      necessitates three generations. The lack of genetic structure of P. ornatus
      population in the South-East Asian archipelago has important implications for the
      sustainable management of this lobster in that the species within the region
      needs to be managed as one genetic stock. 

PMID- 25951346
TI  - Viral elements and host cellular proteins in intercellular movement of Bamboo
      mosaic virus.
AB  - As a member of the genus Potexvirus, Bamboo mosaic virus (BaMV) also belongs to
      the plant viruses that encode triple gene block proteins (TGBps) for
      intercellular movement within the host plants. Recent studies of the movement
      mechanisms of BaMV have revealed similarities and differences between BaMV and
      other potexviruses. This review focuses on the general aspects of viral and host
      elements involved in BaMV movement, the interactions among these elements, and
      the possible pathways for intra- and intercellular trafficking of BaMV. Major
      features of BaMV trafficking that have not been demonstrated in other
      potexviruses include: (i) the involvement of replicase, (ii) fine regulation by
      coat protein phosphorylation, (iii) the key roles played by TGBp3, (iv) the use
      of virions as the major transported form, and (v) the involvement of specific
      host factors, such as Ser/Thr kinase-like protein of Nicotiana benthamiana. We
      also highlight areas for future study that will provide a more comprehensive
      understanding of the detailed interactions among viral movement proteins and host
      factors, as well as the regulatory mechanisms of virus movement. Finally, a model
      based on the current knowledge is proposed to depict the diverse abilities of
      BaMV to utilize a wide range of mechanisms for efficient intercellular movement. 

PMID- 25951347
TI  - Hierarchical feedback modules and reaction hubs in cell signaling networks.
AB  - Despite much effort, identification of modular structures and study of their
      organizing and functional roles remain a formidable challenge in molecular
      systems biology, which, however, is essential in reaching a systematic
      understanding of large-scale cell regulation networks and hence gaining capacity
      of exerting effective interference to cell activity. Combining graph theoretic
      methods with available dynamics information, we successfully retrieved multiple
      feedback modules of three important signaling networks. These feedbacks are
      structurally arranged in a hierarchical way and dynamically produce layered
      temporal profiles of output signals. We found that global and local feedbacks act
      in very different ways and on distinct features of the information flow conveyed
      by signal transduction but work highly coordinately to implement specific
      biological functions. The redundancy embodied with multiple signal-relaying
      channels and feedback controls bestow great robustness and the reaction hubs
      seated at junctions of different paths announce their paramount importance
      through exquisite parameter management. The current investigation reveals
      intriguing general features of the organization of cell signaling networks and
      their relevance to biological function, which may find interesting applications
      in analysis, design and control of bio-networks. 

PMID- 25951348
TI  - Three-photon-excited luminescence from unsymmetrical cyanostilbene aggregates:
      morphology tuning and targeted bioimaging.
AB  - We report an experimental observation of aggregation-induced enhanced
      luminescence upon three-photon excitation in aggregates formed from a class of
      unsymmetrical cyanostilbene derivatives. Changing side chains (-CH3, -C6H13, 
      C7H15O3, and folic acid) attached to the cyanostilbene core leads to
      instantaneous formation of aggregates with sizes ranging from micrometer to
      nanometer scale in aqueous conditions. The crystal structure of a derivative with
      a methyl side chain reveals the planarization in the unsymmetrical cyanostilbene
      core, causing luminescence from corresponding aggregates upon three-photon
      excitation. Furthermore, folic acid attached cyanostilbene forms well-dispersed
      spherical nanoaggregates that show a high three-photon cross-section of 6.0 * 10(
      80) cm(6) s(2) photon(-2) and high luminescence quantum yield in water. In order
      to demonstrate the targeted bioimaging capability of the nanoaggregates, three
      cell lines (HEK293 healthy cell line, MCF7 cancerous cell line, and HeLa
      cancerous cell line) were employed for the investigations on the basis of their
      different folate receptor expression level. Two kinds of nanoaggregates with and
      without the folic acid targeting ligand were chosen for three-photon bioimaging
      studies. The cell viability of three types of cells incubated with high
      concentration of nanoaggregates still remained above 70% after 24 h. It was
      observed that the nanoaggregates without the folic acid unit could not undergo
      the endocytosis by both healthy and cancerous cell lines. No obvious endocytosis
      of folic acid attached nanoaggregates was observed from the HEK293 and MCF7 cell
      lines having a low expression of the folate receptor. Interestingly, a
      significant amount of endocytosis and internalization of folic acid attached
      nanoaggregates was observed from HeLa cells with a high expression of the folate
      receptor under three-photon excitation, indicating targeted bioimaging of folic
      acid attached nanoaggregates to the cancer cell line. This study presents a
      paradigm of using organic nanoaggregates for targeted three-photon bioimaging. 

PMID- 25951349
TI  - Water Structure Recovery in Chaotropic Anion Recognition: High-Affinity Binding
      of Dodecaborate Clusters to gamma-Cyclodextrin.
AB  - Dodecaborate anions of the type B12X12(2-) and B12X11Y(2-) (X=H, Cl, Br, I and
      Y=OH, SH, NH3(+), NR3(+)) form strong (K(a) up to 10(6) L mol(-1), for B12Br12(2
      )) inclusion complexes with gamma-cyclodextrin (gamma-CD). The micromolar
      affinities reached are the highest known for this native CD. The complexation
      exhibits highly negative enthalpies (up to -25 kcal mol(-1)) and entropies
      (TDeltaS up to -18.4 kcal mol(-1), both for B12I12(2-)), which position these
      guests at the bottom end of the well-known enthalpy-entropy correlation for CDs.
      The high driving force can be traced back to a chaotropic effect, according to
      which chaotropic anions have an intrinsic affinity to hydrophobic cavities in
      aqueous solution. In line with this argument, salting-in effects revealed
      dodecaborates as superchaotropic dianions.

PMID- 25951350
TI  - Enolase-1 is a therapeutic target in endometrial carcinoma.
AB  - ENO1 plays a paradoxical role in driving the pathogenesis of tumors. However, the
      clinical significance of ENO1 expression remains unclear and its function and
      modulatory mechanisms have never been reported in endometrial carcinoma (EC). In
      this study, ENO1 silencing significantly reduced cell glycolysis, proliferation,
      migration, and invasion in vitro, as well as tumorigenesis and metastasis in vivo
      by modulating p85 suppression. This in turn mediated inactivation of PI3K/AKT
      signaling and its downstream signals including glycolysis, cell cycle
      progression, and epithelial-mesenchymal transition (EMT)-associated genes. These
      effects on glycolysis and cell growth were not observed after ENO1 suppression in
      normal human endometrial epithelial cells (HEEC). Knocking down ENO1 could
      significantly enhance the sensitivity of EC cells to cisplatin (DDP) and markedly
      inhibited the growth of EC xenografts in vivo. In clinical samples, EC tissues
      exhibited higher expression levels of ENO1 mRNA and protein compared with normal
      endometrium tissues. Patients with higher ENO1 expression had a markedly shorter
      overall survival than patients with low ENO1 expression. We conclude that ENO1
      favors carcinogenesis, representing a potential target for gene-based therapy. 

PMID- 25951352
TI  - Electroclinical features of epileptic encephalopathy caused by SCN8A mutation.
AB  - Voltage-gated sodium channel Nav 1.6, encoded by the gene SCN8A, plays a crucial
      role in controlling neuronal excitability. SCN8A mutations that cause increased
      channel activity are associated with seizures. We describe a patient with
      epileptic encephalopathy caused by de novo SCN8A mutation (c.5614C>T,
      p.Arg1872Trp). Seizures began 10 days after birth at which time brain magnetic
      resonance imaging (MRI) and electroencephalography (EEG) were normal. Seizure
      recurrence increased with age, leading to the development of frequent status
      epilepticus from 1 year of age. Seizure type included generalized tonic seizures
      and focal motor seizures. EEG first showed focal epileptic activity at the age of
      4 months, and thereafter showed multifocal spikes. Serial MRI demonstrated brain
      atrophy, which appeared to progress with seizure aggravation. Clinical features
      that may give a clue to the diagnosis include normal EEG despite frequent
      seizures in early infancy and an increase in epileptic activity that occurs with
      aging. 

PMID- 25951351
TI  - Unlocking the potential of CD70 as a novel immunotherapeutic target for non-small
      cell lung cancer.
AB  - Although normally restricted to activated T and B cells and mature dendritic
      cells, constitutive expression of CD70, a member of the tumor necrosis family,
      has been described in both hematological and solid tumors, where it increases
      tumor cell and regulatory T cell survival by signaling through its receptor,
      CD27.We have assessed the co-expression of CD70 and CD27 in non-small cell lung
      cancer (NSCLC) by immunohistochemistry to explore a correlation between
      expression of the protein and tumor histologic subtype, genetic aberrations and
      prognosis. Furthermore, we tested the ability of ARGX-110, a CD70-blocking
      antibody, to induce NK cell-mediated cytotoxicity.Our results revealed CD70
      expression on the surface of both primary and metastatic NSCLC tumor cells and in
      the tumor microenvironment. Moreover, CD27-expressing tumor infiltrating
      lymphocytes were found adjacent to the tumor cells, suggesting active CD70
      mediated signaling. Finally, we have shown that ARGX-110, has potent cytotoxic
      effects on CD70+ NSCLC cell lines. 

PMID- 25951353
TI  - Evaluation of the Retro-Orbital Fatty Tissue Volume in Delayed Orbital Blow-Out
      Fractures.
AB  - PURPOSE: In patients where diplopia and enophthalmia are manifest, surgical
      intervention is usually necessary. The pathogenesis of these symptoms usually
      includes the prolapse of orbital tissues into the sinus or compression by the
      surrounding bone structures. Although the retro-orbital fatty tissue, orbital
      fascia, and the muscle tissue can be reduced to the original place after being
      incarcerated into the maxillary space, it is obvious that the procedure can lead
      to significant fibrosis in these structures. The authors have aimed to carry out
      a quantitative evaluation of the fatty tissue volumes in patients with repair
      delayed for more than two weeks. METHODS: The preoperative and postoperative
      fatty tissue volumes and the changes in total orbital volume were evaluated by
      using CT on the patients (n = 9) who were consulted to the authors' clinic from
      other health centers. RESULTS: Although no significant correlation was observed
      between the prolapsed volume and the postoperative reduction in the fatty tissue,
      the reduction in the retro-orbital fatty tissue was statistically significant.
      CONCLUSION: Evaluating postoperative retro-orbital fatty tissue volumes may have
      implications for surgical intervention in the future.

PMID- 25951354
TI  - Products of the Major Histocompatibility Complex and CD4/CD8 Cell Infiltration in
      Cervical Intraepithelial Neoplasia and in Cervical Carcinoma.
AB  - OBJECTIVES: Major histocompatibility complex (MHC) products and the CD4/CD8 cell
      ratio in the lymphocyte infiltrate in cervical preneoplastic and neoplastic
      lesions are investigated to determine the correlation between the infiltration of
      lymphocytes in subepithelial stromal tissue and the expression of MHC class I and
      MHC class II antigens on epithelial cells. MATERIALS AND METHODS: The expression
      of MHC products and the lymphocyte infiltration were studied by an indirect
      immunohistochemical staining (alkaline phosphataseanti-alkaline phosphatase) in 6
      biopsies of normal cervical squamous epithelium, in 22 biopsies of cervical
      intraepithelial neoplasia (CIN), and in 9 biopsies of cervical carcinoma.
      Immunohistochemically positive lymphocytes were counted in highpower fields. The
      density of MHC expression in CIN and cervical carcinoma was described
      semiquantitatively in the histological slides. RESULTS: We have seen a number of
      differences in the expression of MHC products between normal cervical squamous
      epithelium and CIN or cervical carcinoma. Our results also show that the CD4/CD8
      cell ratio in normal, in dysplastic, and in malignant cervical tissues differs
      from peripheral blood. We found statistically significant differences (Mann
      Whitney U test, p < .05) between the CD4/CD8 ratio of the normal epithelium when
      compared to the preneoplastic and neoplastic cervical lesions. In the
      histological sections tested, CD8 cells exceeded the number of CD4 cells in CIN
      and cervical carcinoma. Expression of MHC products is independent of the
      infiltration of CD4 and CD8 cells in the tissue of low-grade and high-grade
      cervical squamous intraepithelial lesions (SILs) and in cervical carcinoma.
      CONCLUSIONS: We found a significant decrease of the CD4/CD8 cell ratio in low
      grade SILs, high-grade SILs, and squamous cell carcinoma compared to normal
      cervical epithelium. The loss of MHC class I antigen expression in poorly
      differentiated tumor cells does not correlate with the amount of lymphocyte
      infiltration.

PMID- 25951355
TI  - Evaluation of a new instrument designed for directed cervical excision: cone
      biopsy excisor.
AB  - OBJECTIVE: Our objective was to compare a newly designed instrument, the Cone
      Biopsy Excisor (CBE; Apple Medical Corporation, Bolton, MA), with the standard
      loop electrosurgical excision procedure (LEEP) for providing a cervical
      conization specimen with the best achievable margin quality for histological
      evaluation. METHODS: Patients referred to the dysplasia clinics at Hartford
      Hospital, St. Francis/Mt. Sinai Hospital and the University of Connecticut Health
      Center/New Britain General Hospital were randomized to either the CBE procedure
      or LEEP. To be included in the study, patients had to meet at least one of the
      following criteria: biopsy-proven cervical intraepithelial neoplasia grade 2 or
      3, unsatisfactory colposcopy, positive endocervical curettage, or one or more
      degrees of cytohistological discrepancy. Exclusion criteria included pregnancy,
      undiagnosed uterine bleeding, acute cervicitis, or biopsy-proven invasive
      carcinoma. Forty-seven patients were randomized to the CBE and 48 to LEEP. To
      obtain the cervical specimen, third- and fourth-year obstetricalgynecological
      residents used Force II Valley Lab Generators (Valley Lab, Boulder, CO) at a
      blend one setting (80/20 blend of cutting and coagulation). Wattage ranged from
      25 to 45, according to the size of the instrument used. Pathological reports were
      reviewed by the author to determine the amount of fragmentation and for tissue
      diagnosis. Slides of the specimens were evaluated by two blinded gynecological
      pathologists. The slides were analyzed for margin quality and thermal damage. A
      thermal damage score was assigned, evaluating the number of cells affected and
      the depth of damage. This scoring system, designed by the pathologists, ranged
      from 3 (least thermal damage) to 9 (greatest thermal damage). RESULTS: Of 47 CBE
      cases and 48 LEEP cases, 41 (87%) and 8 (17%), were single specimens X (1) =
      44.6; (p < .0001). The mean number of specimens submitted to pathology per case
      was 1.2 (+/- 0.6) in the CBE group and 2.3 (+/- 0.9) in the LEEP group (t -
      6.89;p < .001). Margins obliterated by thermal artifact included 3 of 47 (6%) in
      the CBE group and 16 of 48 (33%) in the LEEP group (X (1) = 9.16;p < .003). Mean
      thermal damage score was 4.1 (+/- 0.9) in the CBE group and 6.1 (+/- 1.8) in the
      LEEP group (t = 6.77; p < .001). CONCLUSION: The Cone Biopsy Excisor provides a
      cervical specimen that exhibits less fragmentation and less thermal damage and
      has margins that are less likely to be indeterminate than that provided by
      standard LEEP.

PMID- 25951357
TI  - Cytological prediction of cervical intraepithelial neoplasia grade 3: does size
      of the lesion matter?
AB  - OBJECTIVE: Our objective was to test the hypothesis that accurate cytological
      prediction of cervical intraepithelial neoplasia grade 3 (CIN3) is related to the
      size of the atypical transformation zone. PATIENTS AND METHODS: Data on 340 women
      in whom CIN3 was diagnosed after large-loop excision of the transformation zone
      were recorded prospectively on a computerized database. These data were studied
      with regard to such variables as lesion size, age, parity, contraception use, and
      smoking status. RESULTS: No association was demonstrated between cytological
      findings and lesion size in accurately predicting CIN3 lesions. A weak
      association between cytological findings and age was demonstrated: Cytology is
      more likely to predict CIN3 accurately in women 25 years or older than in women
      younger than 25 years. CONCLUSIONS: Accurate cytological prediction of CIN3 is
      not related to the size of the atypical transformation zone seen at colposcopy.
      The CIN3 lesions may be present as discrete foci within a background of low-grade
      changes.

PMID- 25951356
TI  - Improved Accuracy for Cervical Cytology with the ThinPrep Method and the
      Endocervical Brush-Spatula Collection Procedure.
AB  - OBJECTIVE: Our objective was to assess the sensitivity of a fluid-based, thin
      layer slide preparation system (ThinPrep; Cytyc Corporation, Boxborough, MA), as
      compared to conventional Papanicolaou smears obtained with the endocervical brush
      and spatula sampling devices. PATIENTS AND METHODS: Two groups totaling 1,583
      patients, all of whom were attending Planned Parenthood of the Rocky Mountains
      clinics, were included in the study. Cervical cell samples taken with the
      endocervical brush and plastic spatula were used first to make a conventional
      smear. Then the residual cells were rinsed into a vial containing preservative
      fluid, from which a ThinPrep slide was made. Screening and diagnosis of ThinPrep
      and conventional slides were blinded. RESULTS: The ThinPrep method demonstrated
      110% greater detection of low-grade squamous intraepithelial lesions and more
      severe diagnoses as compared to the conventional smear. The ThinPrep method
      yielded 54% more high-grade squamous intraepithelial lesions than did the
      conventional smears. Review by an independent pathologist confirmed the
      significant increase in detection of low-grade squamous intraepithelial lesions
      and more severe diagnoses. CONCLUSION: The data from more than 1,500 patients
      indicate improved sensitivity for the detection of disease with the ThinPrep
      cervical slide preparation method.

PMID- 25951358
TI  - Applications of automation in cervical cancer screening.
AB  - To increase the sensitivity of the cervical Papanicolaou (Pap) smear, several
      automated devices now are commercially available. In the last 2 years, the U.S.
      Food and Drug Administration approved three of these devices, each of which
      operates differently from the others. The ThinPrep 2000 is a method whereby the
      traditional Pap smear is substituted by a liquid-based smear collection technique
      that allows the preparation of thin layers, which addresses the problems of
      obscuring blood, inflammation, and overlapping cells on traditional smears. The
      AutoPap 300 QC is a rescreening device that selects from a batch of negative
      smears the 10% most likely abnormal smears for manual rescreening. The PAPNET
      Testing System is a neural network-based semiautomated screening system used for
      adjunctive testing of negative Pap smears. The system selects and displays the
      most abnormal-looking cells for review by the cytotechnologist, thus improving
      the detection of missed abnormalities. The effectiveness of the introduction of
      these devices for cervical cancer detection is discussed. 

PMID- 25951359
TI  - Improving the screening of cervical precancerous lesions by improving laboratory
      quality assurance in cytology.
AB  - It is well recognized that despite repeated screening, a certain number of women
      continue to develop invasive cervical cancer. This fact emphasizes the importance
      of identifying the potential failures of the detection system and of analyzing
      the reasons for such failures. The quality of cytological diagnoses, particularly
      the high number of false-negative smears, frequently is debated. Sampling errors
      include cell collection (bad sampling and paucicellularity), smear preparation,
      and the presence of blood and inflammation. The need to improve slide quality has
      encouraged the development of a number of devices aimed at automating slide
      making. Screening errors also can result in incorrect diagnoses and have led to
      quality assurance guidelines that are unique to cytology but are not universally
      accepted. In recent years, several commercially sponsored systems have been
      developed that use partial automation of the reading process to improve manual
      quality control. Laboratory quality assurance is necessary. The various options
      described in this article, if applied, should improve the quality of cervical
      cytology. 

PMID- 25951360
TI  - Vulvar intraepithelial neoplasia: a synopsis of recent developments.
AB  - This review highlights recent advances in our understanding of preneoplastic
      squamous lesions of the vulva, from a pathologist's perspective. Vulvar
      intraepithelial neoplasia (VIN) is the preferred nomenclature for these lesions.
      VIN lesions may or may not be symptomatic and have a variable clinical
      appearance. Three histological types of VIN are recognized. Although the term
      bowenoid papulosis was introduced for an entity distinct from VIN, current
      evidence indicates that cases with this clinical pathological presentation are
      better classified as VIN. The natural history of VIN is unpredictable, although
      age is regarded as a risk factor for developing invasive disease. The
      histopathological differential diagnosis of VIN includes several lesions, among
      which is a newly described entity-multinucleated atypia of the vulva. VIN1
      lesions are diagnosed uncommonly. Whereas the incidence of invasive vulvar
      carcinoma in North America has not changed, VIN lesions are being increasingly
      detected. Finally, some histological features of VIN are important to consider
      with respect to therapy. 

PMID- 25951361
TI  - Will human papillomavirus testing find a niche?

PMID- 25951362
TI  - Home study course: winter 1998.

PMID- 25951363
TI  - The american society for colposcopy and cervical pathology.

PMID- 25951364
TI  - Do you feel endocervical sampling needs to be done with satisfactory colposcopy?

PMID- 25951365
TI  - Idiopathic granulomatous inflammation of the female genital tract: a separate
      entity?
AB  - CASE: A 35-year-old woman had recurrent, histologically confirmed idiopathic
      granulomatous inflammatory lesions involving the vulva, anoperineum, vagina, and
      cervix. This is the first report of involvement of the entire lower female
      genital tract in this pathological process. The disease has clinical and
      histological characteristics similar to the genital manifestations of Crohn's
      disease and the MelkerssonRosenthal syndrome (cheilitis granulomatosa of
      Miescher). In some cases, vulvitis granulomatosa has a temporal relationship with
      both of these clinical entities. CONCLUSION: These three diseases-Crohn's
      disease, the Melkersson-Rossenthal syndrome, and vulvitis granulomatosa-could
      reflect identical granulomatous disease, but do not necessarily result from a
      common etiological factor. The treatment of these conditions remains surgical
      excision with or without intralesional corticosteroid injections.

PMID- 25951366
TI  - Patients' Experiences of Nurse-Led Screening for Cardiovascular Risk in
      Rheumatoid Arthritis.
AB  - BACKGROUND: Patients with rheumatoid arthritis (RA) have increased morbidity and
      mortality due to cardiovascular disease (CVD). Screening for cardiovascular risk
      is recommended by the European League Against Rheumatism (EULAR). There is a lack
      of evidence of the experiences of RA patients who are screened for CVD. Such
      information is important in order to organize and further develop screening
      programmes for CVD in patients with RA. The aim of the present study was to
      explore RA patients' experiences of participation in nurse-led screening for CVD
      and to identify key issues for the future organization of screening programmes.
      METHODS: Three qualitative focus group interviews were carried out with 14
      outpatients diagnosed with RA. The participants were stratified into groups,
      depending on whether they had a low-to-moderate or high ten-year risk of
      cardiovascular death according to the European Systematic Coronary Risk
      Evaluation (SCORE) system. Data were analysed using meaning condensation to
      identify key themes. RESULTS: Five themes were identified: reactions to receiving
      the invitation to the screening consultation; screening consultation adapted to
      needs and RA; duration reflected needs; screening consultation brought a sense of
      relief; and motivation and sense of control. Regardless of their CV risk, the
      participants found it important that the screening consultation was adapted to
      their needs and their illness as RA had a major impact on their daily life.
      CONCLUSIONS: When planning future screening programmes for CVD for patients with
      RA, it is important that the screening consultation is individualized and
      tailored to patients' needs and their RA. Copyright (c) 2015 John Wiley & Sons,
      Ltd.

PMID- 25951368
TI  - The Stop-Only-While-Shocking algorithm reduces hands-off time by 17% during
      cardiopulmonary resuscitation - a simulation study.
AB  - INTRODUCTION: Reducing hands-off time during cardiopulmonary resuscitation (CPR)
      is believed to increase survival after cardiac arrests because of the sustaining
      of organ perfusion. The aim of our study was to investigate whether charging the
      defibrillator before rhythm analyses and shock delivery significantly reduced
      hands-off time compared with the European Resuscitation Council (ERC) 2010 CPR
      guideline algorithm in full-scale cardiac arrest scenarios. METHODS: The study
      was designed as a full-scale cardiac arrest simulation study including
      administration of drugs. Participants were randomized into using the Stop-Only
      While-Shocking (SOWS) algorithm or the ERC2010 algorithm. In SOWS, chest
      compressions were only interrupted for a post-charging rhythm analysis and
      immediate shock delivery. A Resusci Anne HLR-D manikin and a LIFEPACK 20
      defibrillator were used. The manikin recorded time and chest compressions.
      RESULTS: Sample size was calculated with an alpha of 0.05 and 80% power showed
      that we should test four scenarios with each algorithm. Twenty-nine physicians
      participated in 11 scenarios. Hands-off time was significantly reduced 17% using
      the SOWS algorithm compared with ERC2010 [22.1% (SD 2.3) hands-off time vs. 26.6%
      (SD 4.8); P<0.05]. CONCLUSION: In full-scale cardiac arrest simulations, a minor
      change consisting of charging the defibrillator before rhythm check reduces hands
      off time by 17% compared with ERC2010 guidelines.

PMID- 25951370
TI  - Is the real-world evidence or hypothesis: a tale of two retrospective studies.

PMID- 25951369
TI  - Overexpression of SIX1 is an independent prognostic marker in stage I-III
      colorectal cancer.
AB  - Epithelial-to-mesenchymal transition (EMT) contributes significantly to tumor
      progression and metastasis. The assessment of EMT-associated transcription
      factors could be a promising approach to identify biomarkers and potential
      therapeutic targets in colorectal cancer. In our study, we focused on the
      transcription factor "Sine oculis homeobox" (SIX) 1, which is a member of the
      superfamily of the homeobox genes and has been described to promote EMT in
      different types of tumors. Immunohistochemistry against SIX1 was performed on
      colorectal mucosa, adenomas, carcinomas-in situ and primary adenocarcinomas. An
      expression score was developed and subsequently assessed for its prognostic value
      in two independent cohorts. Cohort 1 consisted of 128 patients with stage I-III
      colorectal cancer; cohort 2 included 817 patients with stage I-III colorectal
      cancer who had participated in the DACHS study. HCT-116 cells were transfected
      with SIX1 plasmids and subjected to migration and colony formation assays. The
      expression of SIX1 increases gradually from mucosa to colorectal adenocarcinomas
      (p > 0.0001). Univariate and multivariate analyses reveal that high expression of
      SIX1 is associated with decreased overall survival (cohort 1: HR: 4.01, CI: 1.20
      14.07, p = 0.025; cohort 2: HR: 1.43, CI: 1.014-2.02, p = 0.047). Overexpression
      of SIX1 induces a more mesenchymal-like phenotype in HCT-116 cells and enhances
      tumor migration. High expression of SIX1 is an independent prognostic marker in
      colorectal cancer. It might be a promising biomarker to stratify patients into
      different risk groups. Moreover, targeting SIX1 might be a novel therapeutic
      approach in patients with colorectal cancer.

PMID- 25951371
TI  - Almeidea A. St.-Hil. belongs to Conchocarpus J.C. Mikan (Galipeinae, Rutaceae):
      evidence from morphological and molecular data, with a first analysis of subtribe
      Galipeinae.
AB  - Subtribe Galipeinae (tribe Galipeeae, subfamily Rutoideae) is the most diverse
      group of Neotropical Rutaceae, with 28 genera and approximately 130 species. One
      of its genera is Almeidea, whose species are morphologically similar to those of
      the genus Conchocarpus. Species of Almeidea occur in the Atlantic Rain Forest of
      Eastern Brazil, with one species (Almeidea rubra) also present in Bolivia. The
      objective of this study was to perform a phylogenetic analysis of Almeidea, using
      a broader sampling of Galipeinae and other Neotropical Rutaceae, the first such
      study focused on this subtribe. To achieve this objective, morphological data and
      molecular data from the nuclear markers ITS-1 and ITS-2 and the plastid markers
      trnL-trnF and rps16 were obtained. Representatives of eight genera of Galipeinae
      and three genera of Pilocarpinae (included also in Galipeeae) and Hortia (closely
      related to Galipeeae) were used. Five species of Almeidea and seven of
      Conchocarpus were included, given the morphological proximity between these two
      genera. Individual (for each molecular marker) and combined phylogenetic analyses
      were made, using parsimony and Bayesian inference as optimization criteria.
      Results showed Galipeinae as monophyletic, with the species of Almeidea also
      monophyletic (supported by the presence of pantocolporate pollen) and nested in a
      clade with a group of species of Conchocarpus, a non-monophyletic group.
      Additionally, C. concinnus appeared in a group with Andreadoxa, Erythrochiton,
      and Neoraputia, other members of Galipeinae. As a result, Conchocarpus would be
      monophyletic only with the exclusion of a group of species related to C.
      concinnus and with the inclusion of all species of Almeidea with the group of
      species of Conchocarpus that includes its type species, C. macrophyllus. Thus,
      species of Almeidea are transferred to Conchocarpus, and the new combinations are
      made here. 

PMID- 25951367
TI  - Liver receptor homolog-1 (LRH-1): a potential therapeutic target for cancer.
AB  - Liver receptor homolog-1 (LRH-1) is a nuclear receptor involved in various
      biological processes. This nuclear receptor has critical functions in embryonic
      development as well as in adult homeostasis. Although the physiological functions
      of LRH-1 in normal breast, pancreas, and intestine have been widely investigated,
      the dysregulation that occurs during pathological conditions is not well
      understood. LRH-1 has been implicated in pancreatic, breast, and gastrointestinal
      cancer, where it exerts its effect of initiation and progression by promoting
      cell proliferation and metastasis. In addition to mechanistic studies, LRH-1
      agonists and antagonists are being explored. Identification and development of
      endogenous and synthetic ligands has been pursued using computational-based
      structural analysis. Through ligand identification and a thorough understanding
      of the pathological roles of LRH-1, new therapeutic avenues for cancer treatment
      based upon LRH-1 may be a desirable focus for further research. 

PMID- 25951372
TI  - Targeted Therapies for Prostate Cancer.
AB  - New therapies for prostate cancer have emerged over the past three years.
      Nevertheless, none of these agents is curative, and unfortunately, patients often
      ultimately develop resistance to these agents. Therefore, the development of
      innovative and effective therapies that overcome these resistances is necessary.
      Unfortunately, the results of a phase III trial evaluating docetaxel in
      combination with targeted therapies demonstrated no difference in survival.
      Moreover, scarce data on the combination of a targeted therapy with new agents
      are currently available. New trials are investigating these possible combination
      treatments; the results of these (on-going) clinical studies are awaited. 

PMID- 25951373
TI  - Assessing bone accrual in cerebral palsy: new longitudinal data and future needs.

PMID- 25951374
TI  - Old metal oxide clusters in new applications: spontaneous reduction of Keggin and
      Dawson polyoxometalate layers by a metallic electrode for improving efficiency in
      organic optoelectronics.
AB  - The present study is aimed at investigating the solid state reduction of a
      representative series of Keggin and Dawson polyoxometalate (POM) films in contact
      with a metallic (aluminum) electrode and at introducing them as highly efficient
      cathode interlayers in organic optoelectronics. We show that, upon reduction, up
      to four electrons are transferred from the metallic electrode to the POM clusters
      of the Keggin series dependent on addenda substitution, whereas a six electron
      reduction was observed in the case of the Dawson type clusters. The high degree
      of their reduction by Al was found to be of vital importance in obtaining
      effective electron transport through the cathode interface. A large improvement
      in the operational characteristics of organic light emitting devices and organic
      photovoltaics based on a wide range of different organic semiconducting materials
      and incorporating reduced POM/Al cathode interfaces was achieved as a result of
      the large decrease of the electron injection/extraction barrier, the enhanced
      electron transport and the reduced recombination losses in our reduced POM
      modified devices. 

PMID- 25951375
TI  - Coping Strategies and Psychological Outcomes: The Moderating Effects of Personal
      Resiliency.
AB  - Certain coping strategies alleviate stress and promote positive psychological
      outcomes, whereas others exacerbate stress and promote negative psychological
      outcomes. However, the efficacy of any given coping strategy may also depend on
      personal resiliency. This study examined whether personal resiliency moderated
      the effects of task-oriented, avoidance-oriented, and emotion-oriented coping
      strategies on measures of depression, anxiety, stress, positive affect, negative
      affect, and satisfaction with life. Results (N = 424 undergraduates) showed
      higher personal resiliency was associated with greater use of task-oriented
      coping strategies, which were in turn associated with more adaptive outcomes, and
      less reliance on nonconstructive emotion-oriented strategies, which in turn were
      associated with poorer psychological outcomes. In addition, individual
      differences in personal resiliency moderated the effects of task-oriented coping
      on negative affect and of emotion-oriented coping on negative affect and
      depression. Specifically, proactive task-oriented coping was associated with
      greater negative affect for people lower in personal resiliency. Moreover, high
      personal resiliency attenuated the negative effects of emotion-oriented coping on
      depression and negative affect. The effects of avoidance-oriented coping were
      mixed and were not associated with or dependent on levels of personal resiliency.

PMID- 25951376
TI  - How uncommon is tickertaping? Prevalence and characteristics of seeing the words
      you hear.
AB  - Tickertape experience is the subjective phenomenon of routinely visualizing the
      orthographic appearance of words that one hears, speaks, or thinks, like mental
      subtitles in the mind's eye. It has been observed in grapheme-color synesthetes,
      whose letter visualizations are colored, but has been very little studied. We
      report a survey, among 425 Norwegian adults from varied sub-samples, of the
      prevalence, character, and associated skills of tickertaping. Our questionnaire
      was designed to reflect different degrees of automaticity of the experience.
      While strongly automatic tickertaping appeared rare (n = 6; CI95 = 0.6% to 3.2%
      of sample), lesser degrees of text visualization were reported by more than half
      of respondents, indicating a continuity between extreme tickertaping and normal
      cognition. Tickertaping was not strongly associated with greater awareness of an
      inner voice while reading silently. We also found no strong evidence that
      tickertapers are unusually likely to self-report skill in rapidly enumerating
      heard words, or in backward spelling and backward speaking, despite the fact that
      these skills have been observed in single-case studies of tickertapers. The
      qualitative character of tickertaping varied among respondents, and included
      negative experiences. However visualization of letters was predominantly
      uncolored, indicating that tickertaping is a phenomenon in its own right and not
      just a subset of grapheme-color synesthesia. We suggest tickertaping is an
      explicit expression of the close interconnection between phonemic and graphemic
      representations of words which, for reasons we do not yet understand, manifests
      as visual imagery with a varying degree of automaticity. 

PMID- 25951377
TI  - DeTEXT: A Database for Evaluating Text Extraction from Biomedical Literature
      Figures.
AB  - Hundreds of millions of figures are available in biomedical literature,
      representing important biomedical experimental evidence. Since text is a rich
      source of information in figures, automatically extracting such text may assist
      in the task of mining figure information. A high-quality ground truth standard
      can greatly facilitate the development of an automated system. This article
      describes DeTEXT: A database for evaluating text extraction from biomedical
      literature figures. It is the first publicly available, human-annotated, high
      quality, and large-scale figure-text dataset with 288 full-text articles, 500
      biomedical figures, and 9308 text regions. This article describes how figures
      were selected from open-access full-text biomedical articles and how annotation
      guidelines and annotation tools were developed. We also discuss the inter
      annotator agreement and the reliability of the annotations. We summarize the
      statistics of the DeTEXT data and make available evaluation protocols for DeTEXT.
      Finally we lay out challenges we observed in the automated detection and
      recognition of figure text and discuss research directions in this area. DeTEXT
      is publicly available for downloading at http://prir.ustb.edu.cn/DeTEXT/. 

PMID- 25951378
TI  - What are the most popular topics of CMPB in the past 3 years?

PMID- 25951379
TI  - Development of Combined Dry Heat and Chlorine Dioxide Gas Treatment with
      Mechanical Mixing for Inactivation of Salmonella enterica Serovar Montevideo on
      Mung Bean Seeds.
AB  - Foodborne outbreaks have been associated with the consumption of fresh sprouted
      beans. The sprouting conditions of mung bean seeds provide optimal conditions of
      temperature and relative humidity for any potential pathogenic contaminant on the
      seeds to grow. The lack of a kill step postsprouting is a major safety concern.
      Thus, the use of a kill step on the seeds prior to a sprouting step would enhance
      the safety of fresh sprouts. The objective of this work was to evaluate the
      effectiveness of the combined thermal and chlorine dioxide gas (3.5 mg/liter of
      air) treatment with mechanical mixing (tumbling) to eliminate Salmonella on
      artificially inoculated mung bean seeds. Although no viable Salmonella was
      recovered from seeds treated in hot water at 60 degrees C for 2 h, these treated
      seeds failed to germinate. Dry heat treatments (55, 60, or 70 degrees C) for up
      to 8 h reduced Salmonella populations in excess of 3 log CFU/g. The use of
      tumbling, while treating the seeds, resulted in up to 1.6 log CFU/g reduction in
      Salmonella populations compared with no tumbling. Dry heat treatment at 65
      degrees C for 18 h with tumbling resulted in a complete inactivation of
      Salmonella populations on inoculated seeds with low inoculum levels (2.83 log
      CFU/g) as compared with high inoculum levels (4.75 log CFU/g). The increased
      reductions in pathogenic populations on the seeds with the use of tumbling could
      be attributed to increased uniformity of heat transfer and exposure to chlorine
      dioxide gas. All treated seeds were capable of germinating, as well as the
      nontreated controls. These results suggest that this combined treatment would be
      a viable process for enhancing the safety of fresh sprouts. 

PMID- 25951380
TI  - Multiplex PCR-Based Serogrouping and Serotyping of Salmonella enterica from
      Tonsil and Jejunum with Jejunal Lymph Nodes of Slaughtered Swine in Metro Manila,
      Philippines.
AB  - Food poisoning outbreaks and livestock mortalities caused by Salmonella enterica
      are widespread in the Philippines, with hogs being the most commonly recognized
      carriers of the pathogen. To prevent and control the occurrence of S. enterica
      infection in the country, methods were used in this study to isolate and rapidly
      detect, differentiate, and characterize S. enterica in tonsils and jejuna with
      jejunal lymph nodes of swine slaughtered in four locally registered meat
      establishments (LRMEs) and four meat establishments accredited by the National
      Meat Inspection Services in Metro Manila. A total of 480 samples were collected
      from 240 animals (120 pigs from each type of meat establishment). A significantly
      higher proportion of pigs were positive for S. enterica in LRMEs (60 of 120)
      compared with meat establishments accredited by the National Meat Inspection
      Services (38 of 120). More S. enterica-positive samples were found in tonsils
      compared with jejuna with jejunal lymph nodes in LRMEs, but this difference was
      not significant. A PCR assay targeting the invA gene had sensitivity that was
      statistically similar to that of the culture method, detecting 93 of 98 culture
      confirmed samples. Multiplex PCR-based O-serogrouping and H/Sdf I typing revealed
      four S. enterica serogroups (B, C1, D, and E) and six serotypes (Agona,
      Choleraesuis, Enteritidis, Heidelberg, Typhimurium, and Weltevreden),
      respectively, which was confirmed by DNA sequencing of the PCR products. This
      study was the first to report detection of S. enterica serotype Agona in the
      country. 

PMID- 25951381
TI  - Reduction of Surrogates for Escherichia coli O157:H7 and Salmonella during the
      Production of Nonintact Beef Products by Chemical Antimicrobial Interventions.
AB  - The efficacy of chemical antimicrobials for controlling Escherichia coli O157:H7
      and Salmonella during production of marinated nonintact beef products was
      evaluated using nonpathogenic surrogates. Boneless beef strip loins were
      inoculated with either approximately 5.8 or 1.9 log CFU/cm(2) (high and low
      inoculation levels, respectively) of nonpathogenic rifampin-resistant E. coli.
      Inoculated strip loins were chilled at 2 degrees C for 24 h, vacuum packaged, and
      aged for 7 to 24 days at 2 degrees C. After aging, strip loins received no
      treatment (control) or one of five antimicrobial spray treatments: 2.5% L-lactic
      acid (pH 2.6), 5.0% L-lactic acid (pH 2.4), 1,050 ppm of acidified sodium
      chlorite (pH 2.8), 205 ppm of peroxyacetic acid (pH 5.2), or tap water (pH 8.6).
      Mean application temperatures were 53, 26, 20, and 18 degrees C for lactic acid,
      water, peroxyacetic acid, and acidified sodium chlorite treatments, respectively.
      Treated and control strip loins were vacuum tumbled in a commercial marinade.
      Samples were collected throughout the experiment to track the effects of
      antimicrobial treatment and processing on inoculated surrogates. For high
      inoculation strip loins, the 5.0% L-lactic acid treatment was most effective for
      reducing surrogates on meat surfaces before marination, producing a 2.6-log mean
      reduction. Peroxyacetic acid treatment resulted in the greatest reduction of
      surface-located surrogate microorganisms in marinated product. Water treatment
      resulted in greater internalization of surrogate microorganisms compared with the
      control, as determined by enumeration of surrogates from cored samples. Producers
      of nonintact beef products should focus on use of validated antimicrobial sprays
      that maximize microbial reduction and minimize internalization of surface
      bacteria into the finished product. 

PMID- 25951382
TI  - Genetically Marked Strains of Shiga Toxin-Producing O157:H7 and Non-O157
      Escherichia coli: Tools for Detection and Modeling.
AB  - Shiga toxin-producing E. coli (STEC) is an important group of foodborne pathogens
      in the United States and worldwide. Nearly half of STEC-induced diarrheal disease
      in the United States is caused by serotype O157:H7, while non-O157 STEC account
      for the remaining illnesses. Thus, the U.S. Department of Agriculture (USDA) Food
      Safety and Inspection Service has instituted regulatory testing of beef products
      and has a zero-tolerance policy for regulatory samples that test positive for
      STEC O157:H7 and six other non-O157 STEC (serogroups O26, O45, O103, O111, O121,
      and O145). In this study, positive control (PC) strains for the detection of STEC
      O157:H7 and the six USDA-regulated non-O157 STEC were constructed. To ensure that
      the food testing samples are not cross-contaminated by the PC sample, it is
      important that the STEC-PC strains are distinguishable from STEC isolated from
      test samples. The PC strains were constructed by integrating a unique DNA target
      sequence and a gene for spectinomycin (Sp) resistance into the chromosomes of the
      seven STEC strains. End-point and real-time PCR assays were developed for the
      specific detection of the PC strains and were tested using 93 strains of E. coli
      (38 STEC O157:H7, at least 6 strains of each of the USDA-regulated non-O157 STEC,
      and 2 commensal E. coli) and 51 strains of other bacteria (30 species from 20
      genera). The PCR assays demonstrated high specificity for the unique target
      sequence. The target sequence was detectable by PCR after 10 culture passages
      (~100 generations), demonstrating the stability of the integrated target
      sequence. In addition, the strains were tested for their potential use in
      modeling the growth of STEC. Plating the PC strains mixed with ground beef flora
      on modified rainbow agar containing Sp eliminated the growth of the background
      flora that grew on modified rainbow agar without Sp. Thus, these strains could be
      used to enumerate and model the growth of STEC in the presence of foodborne
      background flora. 

PMID- 25951383
TI  - Molecular Subtyping of Shiga Toxin-Producing Escherichia coli Using a Commercial
      Repetitive Sequence-Based PCR Assay.
AB  - PCR-based typing methods, such as repetitive sequence-based PCR (rep-PCR), may
      facilitate the identification of Shiga toxin-producing Escherichia coli (STEC) by
      serving as screening methods to reduce the number of isolates to be processed for
      further confirmation. In this study, we used a commercial rep-PCR typing system
      to generate DNA fingerprint profiles for STEC O157 (n = 60) and non-O157 (n = 91)
      isolates from human, food, and animal samples and then compared the results with
      those obtained from pulsed-field gel electrophoresis (PFGE). Fifteen serogroups
      were analyzed using the Kullback Leibler or extended Jaccard statistical method,
      and the unweighted pair group method of averages algorithm was used to create
      dendrograms. Among the 151 STEC isolates tested, all were typeable by rep-PCR.
      Among the non-O157 isolates, rep-PCR clustered 79 (88.8%) of 89 isolates
      according to serogroup status, with peak differences ranging from 1 (96.4%
      similarity) to 12 (58.7% similarity). The genetic relatedness of the non-O157
      serogroups mirrored the branching of distinct clonal groups elucidated by other
      investigators. Although the discriminatory power of rep-PCR (Simpson's index of
      diversity [SID] = 0.954) for the O157 isolates was less than that of PFGE (SID =
      0.993), rep-PCR was able to identify 29 pattern types, suggesting that this
      method can be used for strain typing, although not to the same level as PFGE.
      Similar results were obtained from analysis of the non-O157 isolates. With rep
      PCR, we assigned non-O157 isolates to 46 pattern types with a SID of 0.977. By
      PFGE, non-O157 STEC strains were divided into 77 pattern types with a SID of
      0.996. Together, these results indicate the ability of the rep-PCR typing system
      to distinguish between and within O157 and non-O157 STEC groups. Rapid PCR-based
      typing methods could be invaluable tools for use in outbreak investigations by
      excluding unrelated STEC isolates within 24 h. 

PMID- 25951384
TI  - Prevalence and Antimicrobial Resistance of Salmonella and Escherichia coli from
      Australian Cattle Populations at Slaughter.
AB  - Antimicrobial agents are used in cattle production systems for the prevention and
      control of bacteria associated with diseases. Australia is the world's third
      largest exporter of beef; however, this country does not have an ongoing
      surveillance system for antimicrobial resistance (AMR) in cattle or in foods
      derived from these animals. In this study, 910 beef cattle, 290 dairy cattle, and
      300 veal calf fecal samples collected at slaughter were examined for the presence
      of Escherichia coli and Salmonella, and the phenotypic AMR of 800 E. coli and 217
      Salmonella isolates was determined. E. coli was readily isolated from all types
      of samples (92.3% of total samples), whereas Salmonella was recovered from only
      14.4% of samples and was more likely to be isolated from dairy cattle samples
      than from beef cattle or veal calf samples. The results of AMR testing
      corroborate previous Australian animal and retail food surveys, which have
      indicated a low level of AMR. Multidrug resistance in Salmonella isolates from
      beef cattle was detected infrequently; however, the resistance was to
      antimicrobials of low importance in human medicine. Although some differences in
      AMR between isolates from the different types of animals were observed, there is
      minimal evidence that specific production practices are responsible for
      disproportionate contributions to AMR development. In general, resistance to
      antimicrobials of critical and high importance in human medicine was low
      regardless of the isolate source. The low level of AMR in bacteria from
      Australian cattle is likely a result of strict regulation of antimicrobials in
      food animals in Australia and animal management systems that do not favor
      bacterial disease. 

PMID- 25951385
TI  - Development of Predictive Models for the Growth Kinetics of Listeria
      monocytogenes on Fresh Pork under Different Storage Temperatures.
AB  - This study was conducted to develop a predictive model to estimate the growth of
      Listeria monocytogenes on fresh pork during storage at constant temperatures (5,
      10, 15, 20, 25, 30, and 35 degrees C). The Baranyi model was fitted to growth
      data (log CFU per gram) to calculate the specific growth rate (SGR) and lag time
      (LT) with a high coefficient of determination (R(2) > 0.98). As expected, SGR
      increased with a decline in LT with rising temperatures in all samples. Secondary
      models were then developed to describe the variation of SGR and LT as a function
      of temperature. Subsequently, the developed models were validated with additional
      independent growth data collected at 7, 17, 27, and 37 degrees C and from
      published reports using proportion of relative errors and proportion of standard
      error of prediction. The proportion of relative errors of the SGR and LT models
      developed herein were 0.79 and 0.18, respectively. In addition, the standard
      error of prediction values of the SGR and LT of L. monocytogenes ranged from 25.7
      to 33.1% and from 44.92 to 58.44%, respectively. These results suggest that the
      model developed in this study was capable of predicting the growth of L.
      monocytogenes under various isothermal conditions. 

PMID- 25951386
TI  - Comparative Efficacy of Potassium Levulinate with and without Potassium Diacetate
      and Potassium Propionate versus Potassium Lactate and Sodium Diacetate for
      Control of Listeria monocytogenes on Commercially Prepared Uncured Turkey Breast.
AB  - We evaluated the efficacy of potassium levulinate (KLEV; 0.0, 1.0, 1.5, and 2.0%)
      with and without a blend of potassium propionate (0.1%) and potassium diacetate
      (0.1%) (KPD) versus a blend of potassium lactate (1.8%) and sodium diacetate
      (0.125%) (KLD) for inhibiting Listeria monocytogenes on commercially prepared,
      uncured turkey breast during refrigerated storage. Product formulated with KLD or
      KLEV (1.5%) was also subsequently surface treated with 44 ppm of a solution of
      lauric arginate (LAE). Slices (ca. 1.25 cm thick and 100 g) of turkey breast
      formulated with or without antimicrobials were surface inoculated on both the top
      and bottom faces to a target level of ca. 3.5 log CFU per slice with a five
      strain cocktail of L. monocytogenes, vacuum sealed, and then stored at 4 degrees
      C for up to 90 days. Without inclusion of antimicrobials in the formulation,
      pathogen levels increased by ca. 5.2 log CFU per slice, whereas with the
      inclusion of 1.0 to 2.0% KLEV pathogen levels increased by only ca. 2.9 to 0.8
      log CFU per slice after 90 days at 4 degrees C. When 1.0% KLEV and KPD were
      included as ingredients, pathogen levels increased by ca. 0.8 log CFU per slice
      after storage at 4 degrees C for 90 days, whereas a decrease of ca. 0.7 log CFU
      per slice was observed when 1.5 or 2.0% KLEV and KPD were included as
      ingredients. When used alone, KPD was not effective (>=5.8-log increase). As
      expected, KLD was effective at suppressing L. monocytogenes in uncured turkey
      breast. When uncured turkey breast was formulated with KLD or KLEV (1.5%) or
      without antimicrobials and subsequently surface treated with LAE, pathogen levels
      decreased by ca. 1.0 log CFU per package within 2 h; no differences (P >= 0.01)
      were observed in pathogen levels for product surface treated with or without LAE
      and stored for 90 days. Our results validate the use of KLEV to inhibit outgrowth
      of L. monocytogenes during refrigerated storage of uncured turkey breast. KLEV is
      at least as effective as KLD as an antilisterial agent. 

PMID- 25951387
TI  - Evaluating Pediococcus acidilactici and Enterococcus faecium NRRL B-2354 as
      Thermal Surrogate Microorganisms for Salmonella for In-Plant Validation Studies
      of Low-Moisture Pet Food Products.
AB  - Pediococcus acidilactici ATCC 8042 and Enterococcus faecium NRRL B-2354 were
      investigated as potential surrogates for Salmonella serovars using thermal death
      time kinetics in products such as dry pet foods. The D-values of P. acidilactici
      ATCC 8042, E. faecium NRRL B-2354, and a cocktail of seven Salmonella serovars
      associated with low-moisture products were determined in a preservative-free dry
      pet food product at moisture levels of 9.1, 17.9, and 27.0% and heated between
      76.7 and 87.8 degrees C. The D-values were calculated by least squares linear
      regression. The D-values of P. acidilactici ATCC 8042 were higher than those for
      the Salmonella serovar cocktail but lower than those for E. faecium NRRL 2354. At
      9.1% moisture, D-values of 6.54, 11.51, and 11.66 min at 76.7 degrees C, 2.66,
      3.22, and 4.08 min at 82.2 degrees C, and 1.07, 1.29, and 1.69 min at 87.8
      degrees C were calculated for Salmonella serovars, P. acidilactici ATCC 8042, and
      E. faecium NRRL B-2354, respectively. The data suggest that the thermal
      inactivation characteristics of P. acidilactici ATCC 8042 can be utilized as a
      surrogate to predict the response of Salmonella in dry pet food products that are
      thermally processed at <90 degrees C. 

PMID- 25951388
TI  - Effect of NaCl Treatments on Tyramine Biosynthesis of Enterococcus faecalis.
AB  - The effect of NaCl stress (0 to 8%, wt/vol) on the growth and tyramine production
      in two Enterococcus faecalis strains was examined during culture time. The growth
      of E. faecalis was inhibited by the increase in NaCl concentration, but tyramine
      production was unaffected. Tyramine accumulated rapidly during the logarithmic
      phase of the strains, and the final tyramine levels were approximately 800
      MUg/ml. Relative gene expression of four genes in the tyrosine decarboxylase
      locus, namely, tyrRS, tyrDC, tyrP, and nhaC, was evaluated at different
      incubation times. The results showed that NaCl stress could upregulate the
      expression of tyrDC and tyrP to improve the tyramine production of a single E.
      faecalis strain under certain conditions, and TyrS could act as a negative
      regulator on the genetic regulation of the tyramine cluster. 

PMID- 25951389
TI  - Impact of Clean-Label Antimicrobials and Nitrite Derived from Natural Sources on
      the Outgrowth of Clostridium perfringens during Cooling of Deli-Style Turkey
      Breast.
AB  - Organic acids and sodium nitrite have long been shown to provide antimicrobial
      activity during chilling of cured meat products. However, neither purified
      organic acids nor NaNO2 is permitted in products labeled natural and both are
      generally avoided in clean-label formulations; efficacy of their replacement is
      not well understood. Natural and clean-label antimicrobial alternatives were
      evaluated in both uncured and in alternative cured (a process that uses natural
      sources of nitrite) deli-style turkey breast to determine inhibition of
      Clostridium perfringens outgrowth during 15 h of chilling. Ten treatments of
      ground turkey breast (76% moisture, 1.2% salt) included a control and four
      antimicrobials: 1.0% tropical fruit extract, 0.7% dried vinegar, 1.0% cultured
      sugar-vinegar blend, and 2.0% lemon-vinegar blend. Each treatment was formulated
      without (uncured) and with nitrite (PCN; 50 ppm of NaNO2 from cultured celery
      juice powder). 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 an additional 10 h. Triplicate samples were
      assayed for growth of C. perfringens at predetermined intervals by plating on
      tryptose-sulfite-cycloserine agar. Uncured control and PCN-only treatments
      allowed for 4.6- and 4.2-log increases at 15 h, respectively, and although all
      antimicrobial treatments allowed less outgrowth than uncured and PCN, the degree
      of inhibition varied. The 1.0% fruit extract and 1.0% cultured sugar-vinegar
      blend were effective at controlling populations at or below initial levels,
      whether or not PCN was included. Without PCN, 0.7% dried vinegar and 2.0% lemon
      vinegar blend allowed for 2.0- and 2.5-log increases, respectively, and ~1.5-log
      increases with PCN. Results suggest using clean-label antimicrobials can provide
      for safe cooling following the study parameters, and greater inhibition of C.
      perfringens may exist when antimicrobials are used with nitrite. 

PMID- 25951390
TI  - Decontamination of Mesquite Pod Flour Naturally Contaminated with Bacillus cereus
      and Formation of Furan by Ionizing Irradiation.
AB  - Mesquite pod flour produced from nitrogen-fixing trees of the Prosopis species
      has a unique aroma and flavor that is preferred by some consumers. Due to the
      presence of wildlife, grazing domestic animals, and insects, the pods have a high
      potential of being contaminated with human pathogenic bacteria, such as Bacillus
      cereus. Nonthermal processing technologies are helpful to reduce the population
      of microorganisms in the flour because heating deteriorates the characteristic
      flavor. A study was conducted to investigate the efficacy of ionizing radiation
      in decontaminating two types of mesquite pod flours (Prosopis alba and Prosopis
      pallida) naturally contaminated with B. cereus and the effects of irradiation on
      the formation of furan, a possible human carcinogen. Results showed that the
      populations of B. cereus were 3.8 and 5.4 log CFU/g in nonirradiated P. alba and
      P. pallida flours, respectively, and populations of microflora, mesophilic
      spores, B. cereus, and B. cereus spores decreased with increasing radiation
      doses. At 6 kGy, the populations fell below 1 log CFU/g. Irradiation at 6 kGy had
      no significant effect on the fructose, glucose, or sucrose content of the flour.
      Nonirradiated P. alba and P. pallida flours contained 13.0 and 3.1 ng/g of furan,
      respectively. Furan levels increased with irradiation doses at rates of 2.3 and
      2.4 ng/g/kGy in the two flours. The level of 3-methylbutanal was reduced or not
      affected by irradiation, while the hexanal level was increased. Our results
      suggested that irradiation was effective in decontaminating contaminated mesquite
      flour. The significance of furan formation and possible changes in flavor due to
      irradiation may need to be further examined. 

PMID- 25951391
TI  - Rapid Detection of Bacillus anthracis in Complex Food Matrices Using Phage
      Mediated Bioluminescence.
AB  - Bacillus anthracis, the causative agent of anthrax, is considered a high-priority
      agent that may be used in a food-related terrorist attack because it can be
      contracted by ingestion and it also forms spores with heat and chemical
      resistance. Thus, novel surveillance methodologies to detect B. anthracis on
      adulterated foods are important for bioterrorism preparedness. We describe the
      development of a phage-based bioluminescence assay for the detection of B.
      anthracis on deliberately contaminated foods. We previously engineered the B.
      anthracis phage Wbeta with genes encoding bacterial luciferase (luxA and luxB) to
      create a "light-tagged" reporter (Wbeta::luxAB) that is able to rapidly detect B.
      anthracis by transducing a bioluminescent signal response. Here, we investigate
      the ability of Wbeta::luxAB to detect B. anthracis Sterne, an attenuated select
      agent strain, in inoculated food (ground beef) and milk (2%, baby formula, and
      half and half) matrices after incubation with spores for 72 h at 4 degrees C as
      per AOAC testing guidelines. The majority of B. anthracis bacilli remained in
      spore form, and thus were potentially infectious, within each of the liquid
      matrices for 14 days. Detection limits were 80 CFU/ml after 7 h of enrichment;
      sensitivity of detection increased to 8 CFU/ml when enrichment was extended to 16
      h. The limit of detection in ground beef was 3.2 * 10(3) CFU/g after 7 h of
      enrichment, improving to 3.2 * 10(2) CFU/g after 16 h. Because the time to result
      is rapid and minimal processing is required, and because gastrointestinal anthrax
      can be fatal, the reporter technology displays promise for the protection of our
      food supply following a deliberate release of this priority pathogen. 

PMID- 25951392
TI  - Occurrence of Vibrio parahaemolyticus, Vibrio cholerae, and Vibrio vulnificus in
      the Aquacultural Environments of Taiwan.
AB  - The occurrence of Vibrio parahaemolyticus, Vibrio vulnificus, and Vibrio cholerae
      in a total of 72 samples from six aquaculture ponds for groupers, milk fish, and
      tilapia in southern Taiwan was examined by the membrane filtration and colony
      hybridization method. The halophilic V. parahaemolyticus was only recovered in
      seawater ponds, with a high isolation frequency of 86.1% and a mean density of
      2.6 log CFU/g. V. cholerae was found in both the seawater and freshwater ponds
      but preferentially in freshwater ponds, with a frequency of 72.2% and a mean
      density of 1.65 log CFU/g. V. vulnificus was identified mainly in seawater ponds,
      with an isolation frequency of 27.8%. The density of V. parahaemolyticus in
      seawater ponds was positively related to water temperature (Pearson correlation
      coefficient, r = 0.555) and negatively related to salinity (r = 2 0.333). The
      density of V. cholerae in all six ponds was positively related to water
      temperature (r = 0.342) and negatively related to salinity (r = 2 0.432). Two
      putatively pathogenic tdh(+) V. parahaemolyticus isolates (1.4% of the samples)
      and no ctx(+) V. cholerae isolates were identified. The experimental results may
      facilitate assessments of the risk posed by these pathogenic Vibrio species in
      Taiwan, where aquaculture provides a large part of the seafood supply. 

PMID- 25951393
TI  - Assessment of microbiological quality of retail fresh sushi from selected sources
      in Norway.
AB  - Retail fresh sushi is gaining popularity in Europe. This study was conducted to
      investigate the microbiological quality of selected samples of fresh sushi with a
      shelf life of 2 to 3 days offered as complete meals in Norwegian supermarkets.
      Analysis of aerobic plate counts in 58 sushi samples from three producers
      revealed large variations in microbiological quality, and 48% of the analyzed
      sushi boxes were rated as unsatisfactory (> 6.0 log CFU/g). Mesophilic Aeromonas
      spp. was detected in 71% of the samples. In a follow-up study, we collected
      products and raw materials directly from the production facility of one producer
      and observed a significant decrease (P < 0.01) in aerobic plate counts compared
      with the initial sampling. The observed difference between products purchased in
      stores compared with those collected directly from the factory suggests that poor
      temperature control during distribution and display in stores leads to reduced
      microbiological quality. Microbiological analysis of the sushi ingredients
      revealed that potentially pathogenic bacteria such as mesophilic Aeromonas spp.
      or bacteria belonging to the Enterobacteriaceae can be introduced into sushi
      through both raw vegetables and fish. The results highlight the importance of
      high quality ingredients and proper temperature control to ensure stable quality
      and safety of these food products. 

PMID- 25951395
TI  - Control of the Biofilms Formed by Curli- and Cellulose-Expressing Shiga Toxin
      Producing Escherichia coli Using Treatments with Organic Acids and Commercial
      Sanitizers.
AB  - Biofilms are a mixture of bacteria and extracellular products secreted by
      bacterial cells and are of great concern to the food industry because they offer
      physical, mechanical, and biological protection to bacterial cells. This study
      was conducted to quantify biofilms formed by different Shiga toxin-producing
      Escherichia coli (STEC) strains on polystyrene and stainless steel surfaces and
      to determine the effectiveness of sanitizing treatments in control of these
      biofilms. STEC producing various amounts of cellulose (n = 6) or curli (n = 6)
      were allowed to develop biofilms on polystyrene and stainless steel surfaces at
      28 degrees C for 7 days. The biofilms were treated with 2% acetic or lactic acid
      and manufacturer-recommended concentrations of acidic or alkaline sanitizers, and
      residual biofilms were quantified. Treatments with the acidic and alkaline
      sanitizers were more effective than those with the organic acids for removing the
      biofilms. Compared with their counterparts, cells expressing a greater amount of
      cellulose or curli formed more biofilm mass and had greater residual mass after
      sanitizing treatments on polystyrene than on stainless steel. Research suggests
      that the organic acids and sanitizers used in the present study differed in their
      ability to control biofilms. Bacterial surface components and cell contact
      surfaces can influence both biofilm formation and the efficacy of sanitizing
      treatments. These results provide additional information on control of biofilms
      formed by STEC. 

PMID- 25951394
TI  - Molecular analysis of skin bacterial assemblages from codfish and pollock after
      dry-salted fish production.
AB  - Dry-salted codfish and pollock are commercially important food products with a
      relatively long shelf life. To date, bacterial assemblages present in these
      products that are relevant for food safety have been monitored using only
      classical molecular and/or cultivation methods. The present study employed a
      rapid and accurate identification method involving PCR with denaturing gradient
      gel electrophoresis and pyrosequencing to characterize the bacterial assemblages
      in the skin of three closely related fishes: Gadus morhua, Gadus macrocephalus,
      and Theragra chalcogramma. This methodology can be crucial for timely
      identification of food spoilage, hazard analysis, and monitoring of critical
      control points during food production. Although all specimens were processed in
      the same factory, there were significant compositional differences in their skin
      bacterial communities. In general, the bacterial community was dominated by gram
      negative species of the Gammaproteobacteria. Pyrosequencing yielded 90, 69, and
      245 operational taxonomic units associated with G. morhua, G. macrocephalus, and
      T. chalcogramma, respectively. The most dominant operational taxonomic units were
      assigned in order to Pseudomonas sp., Serratia marcescens, Salinisphaera sp., and
      Psychrobacter pulmonis. Spoilage and pathogenic bacterial groups were detected in
      all the studied salted gadoid samples. 

PMID- 25951396
TI  - Toxicity of graphene oxide on intestinal bacteria and Caco-2 cells.
AB  - In recent years, novel nanomaterials have received much attention due to their
      great potential for applications in agriculture, food safety, and food packaging.
      Among them, graphene and graphene oxide (GO) are emerging as promising
      nanomaterials that may have a profound impact on food packaging. However, there
      are some concerns from consumers and the scientific community about the potential
      toxicity and biocompatibility of nanomaterials. In this study, we investigated
      the antibacterial properties of GO against human intestinal bacteria. The
      cytotoxicity of GO was also studied in vitro using the Caco-2 cell line derived
      from a colon carcinoma. Electron microscopy was used to investigate the
      morphology of GO and the interaction between GO flakes and Caco-2 cells. GO at
      different concentrations (10 to 500 MUg/ml) exhibited no toxicity against the
      selected bacteria and a mild cytotoxic action on Caco-2 cells after 24 h of
      exposure. The results show that weak adsorption of medium nutrients may
      contribute to GO's low toxicity. This study suggests that GO is biocompatible and
      has a potential to be used in agriculture and food science, indicating that more
      studies are needed to exploit its potential applications. 

PMID- 25951397
TI  - Salmonella in raw chicken meat from the Romanian seaside: frequency of isolation
      and antibiotic resistance.
AB  - The purpose of this study was to investigate the occurrence of Salmonella in raw
      chicken meat samples collected at the Romanian seaside and to evaluate the
      antimicrobial susceptibility of the isolates. In 2012, 317 chicken meat samples
      from slaughterhouses (n = 289) and retail markets (n = 28) were evaluated.
      Overall, 13.2% (42) of the samples contained Salmonella; 12.8% (37) and 17.8% (5)
      from the chicken carcasses at slaughterhouses and the fresh meat from retail
      markets, respectively. Eight serotypes of Salmonella enterica subsp. enterica
      were identified: Infantis (18 isolates), Bredeney (7), Virchow (6), Djugu (4),
      Grampian (4), Brandenburg (1), Derby (1), and Ruzizi (1). The isolates were
      resistant to tetracycline (66.6% of isolates), nalidixic acid (64.3%),
      sulfamethoxazole (64.3%), ciprofloxacin (61.9%), streptomycin (59.5%),
      trimethoprim (33.3%), ampicillin (9.5%), chloramphenicol (7.1%), and gentamicin
      (2.4%). No resistance was found to cefotaxime and ceftazidime. Thirty (71.4%) of
      the 42 tested isolates had multidrug resistance patterns to at least two
      antimicrobials. This survey highlighted a multidrug-resistant Salmonella
      contamination rate in raw chicken meat in this area of Romania, which can
      seriously threaten human health. 

PMID- 25951398
TI  - Development of Bioluminescent Cronobacter sakazakii ATCC 29544 in a Mouse Model.
AB  - Cronobacter sakazakii is an emerging pathogen that causes severe and life
      threatening conditions including meningitis, bacteremia, and necrotizing
      enterocolitis. An animal model study for extrapolation of C. sakazakii infection
      can provide a better understanding of pathogenesis. However, methods for real
      time monitoring of the course of C. sakazakii infection in living animals have
      been lacking. We developed a bioluminescent C. sakazakii strain (ATCC 29544) that
      can be used for real-time monitoring of C. sakazakii infection in BALB/c mice. C.
      sakazakii ATCC 29544 mainly colonized brain, liver, spleen, kidney, and
      gastrointestinal tract, as indicated by bioluminescence imaging. This work
      provides a novel approach for studying the progression of C. sakazakii infection
      and evaluating therapeutics in a living mouse model. 

PMID- 25951399
TI  - Thermal Inactivation of Shiga Toxin-Producing Escherichia coli Cells within Cubed
      Beef Steaks following Cooking on a Griddle.
AB  - Thermal inactivation of Shiga toxin-producing Escherichia coli (STEC) cells
      within knitted/cubed beef steaks following cooking on a nonstick griddle was
      quantified. Both faces of each beef cutlet (ca. 64 g; ca. 8.5 cm length by 10.5
      cm width by 0.75 cm height) were surface inoculated (ca. 6.6 log CFU/g) with 250
      MUl of a rifampin-resistant cocktail composed of single strains from each of
      eight target serogroups of STEC: O26:H11, O45:H2, O103:H2, O104:H4, O111:H(2),
      O121:H19, O145:NM, and O157:H7. Next, inoculated steaks were (i) passed once
      through a mechanical tenderizer and then passed one additional time through the
      tenderizer perpendicular to the orientation of the first pass (single cubed
      steak; SCS) or (ii) passed once through a mechanical tenderizer, and then two
      tenderized cutlets were knitted together by passage concomitantly through the
      tenderizer two additional times perpendicular to the orientation of the previous
      pass (double cubed steak; DCS). SCS and DCS were individually cooked for up to
      3.5 min per side in 30 ml of extra virgin olive oil heated to 191.5 degrees C
      (376.7 degrees F) on a hard-anodized aluminum nonstick griddle using a flat
      surface electric ceramic hot plate. Regardless of steak preparation (i.e., single
      versus double cubed steaks), as expected, the longer the cooking time, the higher
      the final internal temperature, and the greater the inactivation of STEC cells
      within cubed steaks. The average final internal temperatures of SCS cooked for up
      2.5 min and DCS cooked for up to 3.5 min ranged from 59.8 to 94.7 degrees C and
      40.3 to 82.2 degrees C, respectively. Cooking SCS and DCS on an aluminum griddle
      set at ca. 191.5 degrees C for 0.5 to 2.5 min and 1.0 to 3.5 min per side,
      respectively, resulted in total reductions in pathogen levels of ca. 1.0 to >=6.8
      log CFU/g. These data validated that cooking SCS (ca. 0.6 cm thick) or DCS (ca.
      1.3 cm thick) on a nonstick aluminum griddle heated at 191.5 degrees C for at
      least 1.25 and 3.0 min per side, respectively, was sufficient to achieve a 5.0log
      reduction in the levels of the single strains from each of the eight target STEC
      serogroups tested. 

PMID- 25951400
TI  - Characterization of Extended-Spectrum beta-Lactamase-Producing Escherichia coli
      Strains Isolated from Retail Foods in Shaanxi Province, China.
AB  - Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli strains have
      been reported worldwide; however, the incidence and characterization of foodborne
      ESBL-producing E. coli strains have been rarely reported in the People's Republic
      of China. Among a collection of 659 E. coli isolates recovered from retail foods
      in Shaanxi Province, People's Republic of China, 223 cefoxitin-resistant and/or
      cefoperazone-resistant isolates were screened for ESBL production with the double
      disk diffusion test. The ESBL-producing isolates were characterized for
      antimicrobial resistance and the presence of blaTEM, blaSHV, and blaCTX-M genes.
      Isolates with blaCTX-M were further classified by PCR as having blaCTX-M-1,
      blaCTX-M-2, blaCTX-M-8, blaCTX-M-9, or blaCTX-M-25. One hundred forty-seven
      isolates were identified as ESBL positive. PCR detection revealed that 146
      isolates (99.3%) contained the blaCTX-M gene. Among these isolates, 42 (28.8%)
      were positive for the enzyme CTX-M-1, 5 (3.4%) for CTX-M-2, and 99 (67.8%) for
      CTX-M-9. No CTX-M-8 and CTX-M-25 were found in this study. One hundred fifteen
      isolates (78.2%) were positive for the blaTEM gene, but blaSHV was not detected.
      Among the 147 ESBL-producing E. coli isolates, 75 (51.0%), 35 (23.8%), and 4
      (2.7%) isolates were positive for blaTEM and blaCTX-M-9, blaTEM and blaCTX-M-1,
      and blaTEM and blaCTX-M-2, respectively. All of the 147 ESBL-producing isolates
      were resistant to three or more non-beta-lactam antibiotics. This study provides
      evidence that foodborne E. coli can harbor ESBL-encoding genes. Thus, food could
      be a vehicle for the dissemination of ESBL-producing E. coli strains, a situation
      that requires surveillance and appropriate management strategies. 

PMID- 25951401
TI  - Prevalence of Campylobacter spp. in Retail Chicken, Turkey, Pork, and Beef Meat
      in Poland between 2009 and 2013.
AB  - The purpose of the present study was to determine the prevalence of thermophilic
      Campylobacter in poultry, pork, and beef meat at the retail level and to identify
      the main categories of meat representing the most significant reservoirs of
      Campylobacter. A monitoring study was conducted throughout Poland from 2009 to
      2013. A total of 1,700 fresh meat samples were collected from supermarkets, large
      retail outlets, and smaller stores. Thermophilic Campylobacter species were
      detected in 690 (49.3%) of 1,400 poultry samples collected from retail trade.
      Strains were isolated from 50.2 and 41.1% of raw chicken and turkey meat samples,
      respectively, and from 50.1 and 42.6% of raw chicken and turkey giblets. The
      incidence of Campylobacter spp. on pork (10.6%) and beef (10.1%) was
      significantly lower than on poultry. Campylobacter jejuni was the most prevalent
      Campylobacter species in chicken (46.6%), pork (68.6%), and beef (66.7%), and
      Campylobacter coli was the most frequently isolated Campylobacter species in
      turkey meat (71.2%). This study revealed that retail raw meats are often
      contaminated with Campylobacter; however, the prevalence of these pathogens is
      markedly different in different meats. Raw retail meats are potential vehicles
      for transmitting foodborne diseases, and our findings stress the need for
      increased implementation of hazard analysis critical control point programs and
      consumer food safety education efforts. 

PMID- 25951402
TI  - Prevalence and Antimicrobial Resistance of Vibrio parahaemolyticus Isolated from
      Raw Shellfish in Poland.
AB  - Vibrio parahaemolyticus is a marine bacterium recognized as an important cause of
      gastroenteritis in humans consuming contaminated shellfish. In recent years,
      increasing resistance to ampicillin and aminoglycosides has been observed among
      V. parahaemolyticus isolates. However, the first-line antimicrobials such as
      tetracyclines and fluoroquinolones remained highly effective against these
      bacteria. The aim of this study was to evaluate the occurrence of V.
      parahaemolyticus in live bivalve molluscs available on the Polish market and to
      determine the antimicrobial resistance of the recovered isolates. A total of 400
      shellfish samples (mussels, oysters, clams, and scallops) from 2009 to 2012 were
      tested using the International Organization for Standardization standard 21872-1
      method and PCR for the species-specific toxR gene. Antimicrobial susceptibility
      of the isolates was determined using a microbroth dilution method. V.
      parahaemolyticus was identified in 70 (17.5%) of the 400 samples, and the toxR
      gene was confirmed in 64 (91.4%) of these isolates. Most of the isolates were
      recovered from clams (31 isolates; 48.4% prevalence) followed by mussels (17
      isolates; 26.6% prevalence). More V. parahaemolyticus-positive samples were found
      between May and September (22.7% prevalence) than between October and April
      (11.4% prevalence). Antibiotic profiling revealed that most isolates were
      resistant to ampicillin (56 isolates; 87.5%) and to streptomycin (45 isolates;
      70.3%), but all of them were susceptible to tetracycline and chloramphenicol.
      Forty-one isolates (64.1%) were resistant to two or more antimicrobials; however,
      only one isolate (1.6%) was resistant to three antimicrobial classes. The
      antimicrobials used in treatment of human V. parahaemolyticus infection had high
      efficacy against the bacterial isolates tested. This study is the first
      concerning antibiotic resistance of V. parahaemolyticus isolates in Poland, and
      the results obtained indicate that these bacteria may pose a health risk to
      consumers. 

PMID- 25951404
TI  - Detection of Mycobacterium tuberculosis and Mycobacterium avium Complexes by Real
      Time PCR in Bovine Milk from Brazilian Dairy Farms.
AB  - Foodborne diseases are a public health problem worldwide. The consumption of
      contaminated raw milk has been recognized as a major cause of transmission of
      bovine tuberculosis to humans. Other mycobacteria that may be present in raw milk
      and may cause diseases are those belonging to the Mycobacterium avium complex. In
      this study, molecular biology tools were applied to investigate raw milk
      contamination with Mycobacterium spp. in family dairy farms from Rio Grande do
      Sul, southern Brazil. Furthermore, different variables related to the source of
      the milk, herd characteristics, and management were evaluated for their effect on
      milk contamination. Five hundred and two samples were analyzed, of which 354 were
      from the Northwest region (102 farms with samples from 93 bulk tanks and 261
      animals) and 148 from the South region of the state (22 farms with samples from
      23 bulk tanks and 125 animals). Among them, 10 (1.99%) and 7 (1.39%) were
      positive for Mycobacterium tuberculosis (9 confirmed as Mycobacterium bovis) and
      M. avium complexes, respectively. There was no difference in the frequencies of
      positive samples between the regions or the sample sources. Of the positive
      samples, 4 were collected from a bulk tank (1 positive for M. avium and 3 for M.
      tuberculosis). Moreover, 1 sample was positive concomitantly for M. tuberculosis
      and M. avium complexes. On risk analysis, no variable was associated with raw
      milk contamination by M. tuberculosis complex species. However, washing the
      udders of all animals and drying them with paper towels were weakly classified as
      risk factors for M. avium contamination. Positive samples were obtained from both
      animals and bulk tanks, which emphasizes the importance of tuberculosis control
      programs and provides evidence that milk monitoring can be used as a control
      practice. Moreover, the findings of this study reinforce the need for awareness
      of the problems of raw milk consumption among the general population. 

PMID- 25951403
TI  - Low Prevalence of Clostridium difficile in Slaughter Pigs in Korea.
AB  - Clostridium difficile is an important cause of enteric disease in humans and
      animals. The prevalence of C. difficile infection is increasing, and the
      bacterium is frequently found in meat products, suggesting the possibility of
      animal-to-human transmission. Therefore, food animals must be assessed for their
      role as reservoirs of C. difficile. In this study, C. difficile was isolated from
      2 (0.3%) of 659 slaughtered pigs in Korea. Both isolates were characterized as
      ribotype 078 and were multidrug resistant. The low occurrence suggests only a
      limited risk of C. difficile transmission from porcine food products; however, C.
      difficile ribotype 078 is an important pathogen in both pigs and humans, and
      further studies are necessary to investigate the occurrence of C. difficile in
      retail meats and other food animals. 

PMID- 25951405
TI  - Microbiological load and zoonotic agents in beef mortadella from Addis Ababa city
      supermarkets.
AB  - Processing changes the meat ecosystem and, hence, has an impact on the
      microbiological load and quality of the product. Microbial contamination
      decreases shelf life and, if a pathogen is present, increases the risk of
      zoonoses in humans. The aim of this study was to assess the microbiological load,
      including zoonotic agents, in ready-to-eat beef mortadella from Ethiopian
      supermarkets. A total of 119 samples from 8 supermarkets in Addis Ababa City
      (Ethiopia) were examined for aerobic plate count, Enterobacteriaceae, Salmonella,
      and Escherichia coli. An overall mean of 4.0 log for aerobic plate count and 2.2
      log for Enterobacteriaceae was observed. The Salmonella prevalence was 0.8%. An
      overall E. coli prevalence of 29% (range, 13 to 53%) was observed at individual
      supermarkets. 

PMID- 25951406
TI  - Detection of hepatitis A virus in seeded oyster digestive tissue by ricin A
      linked magnetic separation combined with reverse transcription PCR.
AB  - Outbreaks of hepatitis A virus (HAV) infections are most frequently associated
      with the consumption of contaminated oysters. A rapid and selective concentration
      method is necessary for the recovery of HAV from contaminated oysters prior to
      detection using PCR. In this study, ricin extracted from castor beans (Ricinus
      communis) was tested as an alternative to antibody used in immunomagnetic
      separation while concentrating HAV prior to its detection using reverse
      transcription PCR. Initially, the extracted proteins from castor beans were
      fractionated into 13 fractions by gel filtration chromatography. Pretreatment of
      different protein fractions showed a variation in binding of HAV viral protein
      (VP) 1 to oyster digestive tissue in the range of 25.9 to 63.9%. The protein
      fraction, which caused the highest reduction in binding of VP1 to the tissue, was
      identified as ricin A by quadrupole time-of-flight mass spectrometry. Ricin A
      could significantly inhibit binding of VP1 to the tissue with a 50% inhibitory
      concentration of 4.5 MUg/ml and a maximal inhibitory concentration of 105.2%. The
      result showed that the rate of inhibition of HAV binding to tissue was higher
      compared to the rate of ricin itself binding to HAV (slope: 0.0029 versus
      0.00059). However, ricin A concentration showed a higher correlation to the
      relative binding of ricin itself to HAV than the inhibition of binding of HAV to
      the tissue (coefficient of determination, R(2): 0.9739 versus 0.6804). In
      conclusion, ricin A-linked magnetic bead separation combined with reverse
      transcription PCR can successfully detect HAV in artificially seeded oyster
      digestive tissue up to a 10(-4) dilution of the virus stock (titer: 10(4) 50%
      tissue culture infective dose per ml). 

PMID- 25951407
TI  - Effect of Wheat Flour Packaging Materials on Infestation by Lasioderma serricorne
      (F.).
AB  - The ability of the cigarette beetle, Lasioderma serricorne (F.) (Coleoptera:
      Anobiidae), to infest wheat flour under packaged and unpackaged conditions was
      investigated in the laboratory at 27 +/- 2 degrees C and 75% +/- 5% relative
      humidity. Five common packaging materials, namely, vacuum plastic bags, kraft
      paper bags, nonwoven cloth bags, aluminum foil bags, and woven plastic bags, were
      investigated. Adults and eggs of L. serricorne were released on different
      packaged wheat flour or on unpackaged wheat flour, and infestation levels (number
      of live adults and larvae) were determined after 45 days. When adults were
      released on wheat flour, the infestation degree varied depending on the package
      materials. The highest infestation was observed in refined wheat flour packaged
      in nonwoven cloth bags. With wheat flour packaged in kraft paper bags exposed to
      adults or eggs, there was no insect infestation or insect infestation was
      negligible (mean population, <1.3). With wheat flour packaged in aluminum foil
      bags and vacuum plastic bags exposed to adults or eggs, there was no insect
      infestation. Damage to the packaging materials along the folds or edges was found
      in nonwoven cloth bags and woven plastic bags. Therefore, both aluminum foil and
      plastic bags had the greatest resistance to package invasion by L. serricorne. 

PMID- 25951408
TI  - Unfolding grain size effects in barium titanate ferroelectric ceramics.
AB  - Grain size effects on the physical properties of polycrystalline ferroelectrics
      have been extensively studied for decades; however there are still major
      controversies regarding the dependence of the piezoelectric and ferroelectric
      properties on the grain size. Dense BaTiO3 ceramics with different grain sizes
      were fabricated by either conventional sintering or spark plasma sintering using
      micro- and nano-sized powders. The results show that the grain size effect on the
      dielectric permittivity is nearly independent of the sintering method and
      starting powder used. A peak in the permittivity is observed in all the ceramics
      with a grain size near 1 MUm and can be attributed to a maximum domain wall
      density and mobility. The piezoelectric coefficient d33 and remnant polarization
      Pr show diverse grain size effects depending on the particle size of the starting
      powder and sintering temperature. This suggests that besides domain wall density,
      other factors such as back fields and point defects, which influence the domain
      wall mobility, could be responsible for the different grain size dependence
      observed in the dielectric and piezoelectric/ferroelectric properties. In cases
      where point defects are not the dominant contributor, the piezoelectric constant
      d33 and the remnant polarization Pr increase with increasing grain size. 

PMID- 25951409
TI  - Phosphine fumigation and residues in dry-cured ham in commercial applications.
AB  - Dry-cured hams often become infested with ham mites (Tyrophagus putrescentiae)
      during the aging process. Methyl bromide has been used to fumigate dry cured ham
      plants and is the only available fumigant that is effective at controlling ham
      mite infestations. However, methyl bromide will eventually be phased out of all
      industries. This research was designed to determine the efficacy of phosphine
      fumigation at controlling ham mites and red-legged beetles and any impact of
      phosphine fumigation on the sensory quality and safety of dry cured hams.
      Fumigation trials were conducted in simulated ham aging houses and commercial ham
      aging houses. Mite postembryonic mortality was 99.8% in the simulated aging
      houses and >99.9% in commercial aging houses three weeks post fumigation. Sensory
      tests with trained panelists indicated that there were no detectable differences
      (P > 0.05) between phosphine fumigated and control hams. In addition, residual
      phosphine concentration was below the legal limit of 0.01 ppm in ham slices that
      were taken from phosphine fumigated hams.

PMID- 25951410
TI  - Eating marshmallows reduces ileostomy output: a randomized crossover trial.
AB  - AIM: Anecdotally, many ostomates believe that eating marshmallows can reduce
      ileostomy effluent. There is a plausible mechanism for this, as the gelatine
      contained in marshmallows may thicken small bowel fluid, but there is currently
      no evidence that this is effective. METHOD: This was a randomized crossover
      trial. Adult patients with well-established ileostomies were included. Ileostomy
      output was measured for 1 week during which three marshmallows were consumed
      three times daily, and for one control week where marshmallows were not eaten.
      There was a 2-day washout period. Patients were randomly allocated to whether the
      control or intervention week occurred first. In addition, a questionnaire was
      administered regarding patient's subjective experience of their ileostomy
      function. RESULTS: Thirty-one participants were recruited; 28 completed the
      study. There was a median reduction in ileostomy output volume of 75 ml per day
      during the study period (P = 0.0054, 95% confidence interval 23.4-678.3) compared
      with the control week. Twenty of 28 subjects (71%) experienced a reduction in
      their ileostomy output, two had no change and six reported an increase. During
      the study period, participants reported fewer ileostomy bag changes (median five
      per day vs six in the control period, P = 0.0255). Twenty of 28 (71%) reported
      that the ileostomy effluent was thicker during the study week (P = 0.023).
      Overall 19 (68%) participants stated they would use marshmallows in the future if
      they wanted to reduce or thicken their ileostomy output. CONCLUSION: Eating
      marshmallows leads to a small but statistically significant reduction in
      ileostomy output.

PMID- 25951411
TI  - Intramuscular injection of "site enhancement oil": forensic considerations.
AB  - The use of intramuscular injection of foreign substances for aesthetic purposes
      is well known. Complications are usually local to the site of injection but can
      be potentially lethal. Here, we present a case of "site enhancement oil" use in a
      42-year-old man who died from asphyxia due to hanging. Macroscopic and
      microscopic changes as well as computed tomographic changes in injected
      musculature are described and the potentially lethal adverse effects after site
      enhancement oil use are warranted. 

PMID- 25951413
TI  - Effects of Age, Sex, and Body Position on Orofacial Muscle Tone in Healthy
      Adults.
AB  - PURPOSE: Quantification of tissue stiffness may facilitate identification of
      abnormalities in orofacial muscle tone and thus contribute to differential
      diagnosis of dysarthria. Tissue stiffness is affected by muscle tone as well as
      age-related changes in muscle and connective tissue. METHOD: The Myoton-3
      measured tissue stiffness in 40 healthy adults, including equal numbers of men
      and women in each of two age groups: 18-40 years and 60+ years. Data were
      collected from relaxed muscles at the masseter, cheek, and lateral tongue
      surfaces in two positions: reclined on the side and seated with head tilted.
      RESULTS: Tissue stiffness differed across age, sex, and measurement site with
      multiple interaction effects. Overall, older subjects exhibited higher stiffness
      coefficients and oscillation frequency measures than younger subjects whereas sex
      differences varied by tissue site. Effects of body position were inconsistent
      across tissue site and measurement. CONCLUSIONS: Although older subjects were
      expected to have lower muscle tone, age-related nonmuscular tissue changes may
      have contributed to yield a net effect of higher stiffness. These data raise
      several considerations for the development of accurate normative data and for
      future diagnostic applications of tissue stiffness assessment.

PMID- 25951412
TI  - Post-expression strategies for structural investigations of membrane proteins.
AB  - Currently, membrane proteins only comprise 1.5% of the protein data bank and,
      thus, still remain a challenge for structural biologists. Expression,
      stabilization in membrane mimics (e.g. detergent), heterogeneity (conformational
      and chemical), and crystallization in the presence of a membrane mimic are four
      major bottlenecks encountered. In response, several post-expression protein
      modifications have been utilized to facilitate structure determination of
      membrane proteins. This review highlights four approaches: limited proteolysis,
      deglycosylation, cysteine alkylation, and lysine methylation. Combined these
      approaches have facilitated the structure determination of more than 40 membrane
      proteins and, therefore, are a useful addition to the membrane protein structural
      biologist's toolkit. 

PMID- 25951414
TI  - Characterization and antivirus activities of a novel bovine IFN-omega24.
AB  - A novel bovine interferon-omega (BoIFN-omega) gene, which encodes a protein of
      195 amino acids with a 23-amino acid signal peptide, was amplified from bovine
      liver genomic DNA through PCR and named BoIFN-omega24 according to its position
      in the bovine genome. In this study, the recombinant protein was expressed in
      Escherichia coli and antiviral or antiproliferation activity was determined in
      vitro. Results showed that BoIFN-omega24 exhibits high antiviral activity, which
      can be abrogated using PAb against BoIFN-omega24, and inhibits cell
      proliferation. BoIFN-omega24 also presents high sensitivity to trypsin and
      stability at pH 2.0 or 65 degrees C, which are typical characteristics of type I
      IFN. This study revealed that BoIFN-omega24 is a potential novel effective
      therapeutic agent and provided a basis for further research on the BoIFN-omega
      multigene family.

PMID- 25951415
TI  - The effect of crystal packing and Re(IV) ions on the magnetisation relaxation of
      [Mn6]-based molecular magnets.
AB  - The energy barrier to magnetisation relaxation in single-molecule magnets (SMMs)
      proffers potential technological applications in high-density information storage
      and quantum computation. Leading candidates amongst complexes of 3d metals ions
      are the hexametallic family of complexes of formula [Mn6 O2 (R-sao)6 (X)2
      (solvent)y ] (saoH2 =salicylaldoxime; X=mono-anion; y=4-6; R=H, Me, Et, and Ph).
      The recent synthesis of cationic [Mn6 ][ClO4 ]2 family members, in which the
      coordinating X ions were replaced with non-coordinating anions, opened the
      gateway to constructing families of novel [Mn6 ] salts in which the identity and
      nature of the charge balancing anions could be employed to alter the physical
      properties of the complex. Herein we demonstrate initial experiments to show that
      this is indeed possible. By replacing the diamagnetic ClO4 (-) anions with the
      highly anisotropic Re(IV) ion in the form of [Re(IV) Cl6 ](2-) , the energy
      barrier to magnetisation relaxation is increased by up to 30 %. 

PMID- 25951416
TI  - 5-HT3 Receptor Brain-Type B-Subunits are Differentially Expressed in Heterologous
      Systems.
AB  - Genes for five different 5-HT3 receptor subunits have been identified. Most of
      the subunits have multiple isoforms, but two isoforms of the B subunits, brain
      type 1 (Br1) and brain-type 2 (Br2) are of particular interest as they appear to
      be abundantly expressed in human brain, where 5-HT3B subunit RNA consists of
      approximately 75% 5-HT3Br2, 24% 5-HT3Br1, and <1% 5-HT3B. Here we use two
      electrode voltage-clamp, radioligand binding, fluorescence, whole cell, and
      single channel patch-clamp studies to characterize the roles of 5-HT3Br1 and 5
      HT3Br2 subunits on function and pharmacology in heterologously expressed 5-HT3
      receptors. The data show that the 5-HT3Br1 transcriptional variant, when
      coexpressed with 5-HT3A subunits, alters the EC50, nH, and single channel
      conductance of the 5-HT3 receptor, but has no effect on the potency of
      competitive antagonists; thus, 5-HT3ABr1 receptors have the same characteristics
      as 5-HT3AB receptors. There were some differences in the shapes of 5-HT3AB and 5
      HT3ABr1 receptor responses, which were likely due to a greater proportion of
      homomeric 5-HT3A versus heteromeric 5-HT3ABr1 receptors in the latter, as
      expression of the 5-HT3Br1 compared to the 5-HT3B subunit is less efficient.
      Conversely, the 5-HT3Br2 subunit does not appear to form functional channels with
      the 5-HT3A subunit in either oocytes or HEK293 cells, and the role of this
      subunit is yet to be determined. 

PMID- 25951417
TI  - Comparative Study Between Laparoscopic Heller Myotomy Versus Pneumatic Dilatation
      for Treatment of Early Achalasia: A Prospective Randomized Study.
AB  - INTRODUCTION: Achalasia is an incurable primary motor disorder of the esophagus.
      The best treatment modality for achalasia is still controversial. This study
      compared the short- and intermediate-term outcome between endoscopic pneumatic
      dilatation (EPD) versus laparoscopic esophageal myotomy (LEM) for the management
      of adult patients with early-stage achalasia. PATIENTS AND METHODS: This was a
      prospective randomized controlled study of adult patients (20-50 years old) who
      presented with early-stage achalasia (esophageal diameter of <3.5 cm on contrast
      esophagography). Patients were classified into two groups according to the method
      of management: Group A patients were treated with LEM, whereas Group B patients
      were treated with EPD. Follow-up evaluations were conducted at 1 week, 3 months,
      6 months, and then 1 year. RESULTS: In total, 50 patients were managed for a
      manometrically confirmed diagnosis of achalasia. The median age of presentation
      was 31.5 years, with a male-to-female ratio of 0.4:1. Both groups were comparable
      regarding patient demographics and preoperative severity of the condition. The
      rate of symptoms relief was 76% in EPD compared with 96% in LEM (P=.04). There
      was a significant lowering of lower esophageal sphincter in the LEM group
      (P=.0001). Perforation of the esophagus occurred in 8% of the patients during
      EPD, whereas mucosal tears occurred in 4% of the patients during LEM. Reflux
      symptoms developed in 28% and 16% of the patients in the EPD and LEM groups,
      respectively. CONCLUSIONS: LEM was more effective clinically and manometrically
      for patients with early-stage achalasia than EPD. There was no significant
      difference between the two procedures regarding complications.

PMID- 25951418
TI  - End-of-life palliative oral care in Norwegian health institutions. An exploratory
      study.
AB  - OBJECTIVE: To explore circumstances surrounding procedures and knowledge
      regarding oral care for terminal patients in Norwegian healthcare institutions.
      METHODS: A questionnaire was distributed to randomly selected hospitals (n = 19)
      and nursing homes (n = 57) in central and rural parts of Norway. The
      questionnaire included three closed-ended and three open-ended questions about
      oral care for terminal patients. If procedures existed, the respondents were
      asked to enclose or describe them. RESULTS: The response rate was 84% for
      hospitals and 79% for nursing homes. Of the responding institutions, 25% had no
      oral care procedures, nor did 48% recognise their importance. Insufficient
      knowledge about oral care was reported by 39%. Twenty-one different procedures
      were identified, and a great number of oral care products used. The most common
      was glycerol, used by 36% of the institutions. Only 2% used a concentration below
      30% - the limit above which the glycerol has a desiccating rather than a
      moistening effect. The most common patient complaint was dry mouth (49%),
      followed by plaque, food particles and fungus infections, each experienced by
      19%. The most common problem for the personnel was lack of knowledge (43%) and
      patient cooperation (38%). CONCLUSIONS: Some terminal patients do not receive
      adequate palliative oral care in Norwegian healthcare institutions. Those that do
      are exposed to a great number of undocumented procedures and sometimes harmful
      products. There is a need for evidence-based procedures for oral care for
      terminally ill patients in health institutions, establishing interprofessional
      palliative healthcare teams and in particular improved training of the nursing
      staff.

PMID- 25951419
TI  - Is there a two-way relationship between cynicism and job strain? Evidence from a
      prospective population-based study.
AB  - OBJECTIVE: To examine the bidirectional relationship between job strain and
      cynicism. METHODS: The study sample was obtained from the Young Finns study and
      comprised 757 participants (399 women, 53%). The bidirectional association
      between cynicism and job strain over a 6-year-follow-up was examined with a cross
      lagged structural equation model, controlling for a number of demographic
      variables. RESULTS: High job strain (beta = 0.08; P = 0.007) was associated with
      higher baseline-adjusted cynicism 6 years later. Nevertheless, cynicism was not
      associated with baseline-adjusted job strain. The additional analysis showed that
      cynicism mediated 21.5% of the relationship between job strain and depression.
      CONCLUSIONS: Perceptions of having a highly strenuous job may elicit mistrustful
      and cynical attitudes in employees, which in turn may lead to mental health
      problems.

PMID- 25951420
TI  - Associations of Ozone and PM2.5 Concentrations With Parkinson's Disease Among
      Participants in the Agricultural Health Study.
AB  - OBJECTIVE: This study describes associations of ozone and fine particulate matter
      with Parkinson's disease observed among farmers in North Carolina and Iowa.
      METHODS: We used logistic regression to determine the associations of these
      pollutants with self-reported, doctor-diagnosed Parkinson's disease. Daily
      predicted pollutant concentrations were used to derive surrogates of long-term
      exposure and link them to study participants' geocoded addresses. RESULTS: We
      observed positive associations of Parkinson's disease with ozone (odds ratio =
      1.39; 95% CI: 0.98 to 1.98) and fine particulate matter (odds ratio = 1.34; 95%
      CI: 0.93 to 1.93) in North Carolina but not in Iowa. CONCLUSIONS: The
      plausibility of an effect of ambient concentrations of these pollutants on
      Parkinson's disease risk is supported by experimental data demonstrating damage
      to dopaminergic neurons at relevant concentrations. Additional studies are needed
      to address uncertainties related to confounding and to examine temporal aspects
      of the associations we observed.

PMID- 25951421
TI  - Medical marijuana in the workplace: challenges and management options for
      occupational physicians.
AB  - Although possession and use of marijuana is prohibited by federal law,
      legalization in four states (Alaska, Colorado, Oregon, and Washington) and
      allowance for palliation and therapy in 19 others may reposition the drug away
      from the fringes of society. This evolving legal environment, and growing
      scientific evidence of its effectiveness for select health conditions, requires
      assessment of the safety and appropriateness of marijuana within the American
      workforce. Although studies have suggested that marijuana may be used with
      reasonable safety in some controlled environments, there are potential
      consequences to its use that necessitate employer scrutiny and concern. Several
      drug characteristics must be considered, including Delta-tetrahydrocannabinol
      (Delta-THC, or THC) concentration, route of administration, dose and frequency,
      and pharmacokinetics, as well as the risks inherent to particular workplace
      environments. 

PMID- 25951422
TI  - Integrating health and safety in the workplace: how closely aligning health and
      safety strategies can yield measurable benefits.
AB  - OBJECTIVE: To better understand how integrating health and safety strategies in
      the workplace has evolved and establish a replicable, scalable framework for
      advancing the concept with a system of health and safety metrics, modeled after
      the Dow Jones Sustainability Index. METHODS: Seven leading national and
      international programs aimed at creating a culture of health and safety in the
      workplace were compared and contrasted. RESULTS: A list of forty variables was
      selected, making it clear there is a wide variety of approaches to integration of
      health and safety in the workplace. CONCLUSION: Depending on how well developed
      the culture of health and safety is within a company, there are unique routes to
      operationalize and institutionalize the integration of health and safety
      strategies to achieve measurable benefits to enhance the overall health and well
      being of workers, their families, and the community.

PMID- 25951425
TI  - Musculoskeletal ultrasound in American Occupational Medicine Residency Programs:
      a survey of program directors.

PMID- 25951426
TI  - Tacrolimus 0.03% ointment in labial discoid lupus erythematosus: A randomized,
      controlled clinical trial.
AB  - In this randomized, controlled clinical trial to compare efficacy and safety, 41
      patients with labial discoid lupus erythematosus (DLE) were randomized to 2
      groups, either receiving tacrolimus 0.03% ointment (n = 22) or triamcinolone
      acetonide 0.1% cream (n = 19). Each patient was treated with 3, 2, and 1 daily
      doses in the first, second, and third weeks, respectively, for 1 course. After
      the 3 week treatment, patients with complete disappearance of erosion were
      followed up for 3 months. After the 3 week application, 20 participants in the
      tacrolimus group and 19 in the triamcinolone acetonide group completed the study.
      The rates of complete response were 70% and 89.5% in tacrolimus-treated and
      triamcinolone acetonide-treated patients, respectively, with no significant
      difference (P = .235). Reduction in erosion and erythema showed no significant
      difference between groups (P > .05). Final reduction in reticulation areas and
      numeric rating scale scores were significantly greater in the tacrolimus group
      than in the triamcinolone acetonide group (P = .013; P = .048, respectively).
      Only 1 patient receiving tacrolimus presented with slight discomfort. There was
      no significant difference in 3 month recurrence rate between the groups (P >
      .05). Topical tacrolimus is considered as effective as triamcinolone acetonide
      for the management of labial DLE.

PMID- 25951427
TI  - Dietary fatty acids affect semen quality: a review.
AB  - Mammalian spermatozoa are characterized by a high proportion of polyunsaturated
      fatty acids (PUFA) which play a crucial role in fertilization. This review
      focuses on analysis of sperm fatty acid profiles and the effects of omega-3,
      saturated and trans dietary and sperm fatty acids on sperm parameters. Two major
      points have been pivotal points of investigation in the field of sperm fatty acid
      profiles: first, the comparison between fatty acid profiles of fertile and
      infertile men and second, the effect of dietary fatty acids on sperm fatty acid
      profiles as well as sperm quality and quantity. Docosahexaenoic acid (DHA, C22:6n
      3), and palmitic acid (C16:0) are the predominant PUFA and saturated fatty acids,
      respectively, in human sperm cells. Higher levels of DHA are concentrated on the
      sperm's head or tail varying among different species. However, the human sperm
      head contains a higher concentration of DHA. Dietary fatty acids influence on
      sperm fatty acid profiles and it seems that sperm fatty acid profiles are most
      sensitive to dietary omega-3 PUFA. Although improvements in sperm parameters are
      a response to omega-3 sources after more than 4 weeks of supplementation in the
      male diet, time-dependent and dose-dependent responses may explain the failure in
      some experiments. In human spermatozoa, elevated saturated or trans fatty acid
      concentration and a low DHA level is a concern. The regulations of the sperm
      fatty acid mean melting point as well as expression regulation of peroxisome
      proliferator-activated receptor gamma (PPARG) alongside with spermatozoon
      assembly, anti-apoptosis effects, eicosanoid formation, and hormone activity are
      the putative key factors that induce a response by inclusion of omega-3 PUFA.

PMID- 25951428
TI  - IPeak: An open source tool to combine results from multiple MS/MS search engines.
AB  - Liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) is an important
      technique for detecting peptides in proteomics studies. Here, we present an open
      source software tool, termed IPeak, a peptide identification pipeline that is
      designed to combine the Percolator post-processing algorithm and multi-search
      strategy to enhance the sensitivity of peptide identifications without
      compromising accuracy. IPeak provides a graphical user interface (GUI) as well as
      a command-line interface, which is implemented in JAVA and can work on all three
      major operating system platforms: Windows, Linux/Unix and OS X. IPeak has been
      designed to work with the mzIdentML standard from the Proteomics Standards
      Initiative (PSI) as an input and output, and also been fully integrated into the
      associated mzidLibrary project, providing access to the overall pipeline, as well
      as modules for calling Percolator on individual search engine result files. The
      integration thus enables IPeak (and Percolator) to be used in conjunction with
      any software packages implementing the mzIdentML data standard. IPeak is freely
      available and can be downloaded under an Apache 2.0 license at
      https://code.google.com/p/mzidentml-lib/. 

PMID- 25951429
TI  - Structurally Rigid 9-Amino-benzo[c]cinnoliniums Make Up a Class of Compact and
      Large Stokes-Shift Fluorescent Dyes for Cell-Based Imaging Applications.
AB  - Classic fluorescent dyes, such as coumarin, naphthalimide, fluorescein, BODIPY,
      rhodamine, and cyanines, are cornerstones of various spectroscopic and
      microscopic methods, which hold a prominent position in biological studies. We
      recently found that 9-amino-benzo[c]cinnoliniums make up a novel group of
      fluorophores that can be used in biological studies. They are featured with a
      succinct conjugative push-pull backbone, a broad absorption band, and a large
      Stokes shift. They are potentially useful as a small-molecule alternative to R
      phycoerythrin to pair with fluorescein in multiplexing applications. 

PMID- 25951430
TI  - Frequency and Characteristics of Facial Asymmetry in Patients With Deviated
      Noses.
AB  - IMPORTANCE: Facial asymmetry is frequently detected in patients who are seeking
      rhinoplasty for a deviated nose, and its presence often leads to failure to
      create a straight-looking nose. OBJECTIVE: To analyze the frequency and
      characteristics of facial asymmetry in patients with a deviated nose and to
      identify representative parameters to describe types and severity of facial
      asymmetry. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of at a
      tertiary referral center of preoperative photographs of 152 patients who
      underwent rhinoplasty for a deviated nose between January 2008 and December 2012.
      The incidence of facial asymmetry in these patients was compared with the
      incidence in 60 control patients undergoing septoplasty without external nose
      deviation. INTERVENTIONS: Using frontal photographs, the presence of facial
      asymmetry and the types of deviated nose were noted and measured by 2 observers.
      MAIN OUTCOMES AND MEASURES: Facial asymmetry was categorized into 4 types
      depending on which subunit of the face was affected, and deviated nose shapes
      were classified into 5 types. Anthropometric measurements were also performed.
      RESULTS: Facial asymmetry was more common in patients with a deviated nose (84 of
      152 [55%]) than in controls (19 of 60 [32%]) (P = .04). Mixed-type facial
      asymmetry was the most common type in the patient group. Among the anthropometric
      measurement parameters, the distance between the midpoint of the interpupil line
      to the most prominent malar point, lateral canthal angle, lateral alar angle, lip
      margin angle, and tilted chin angle were significantly different between the
      patient group and the control group (P < .05 for all comparisons). There was no
      difference in the incidence of asymmetry with respect to deviation type.
      CONCLUSIONS AND RELEVANCE: Facial asymmetry was more common in patients with a
      deviated nose than in control patients, and mixed-type facial asymmetry was the
      asymmetry most often associated with deviated nose. This study suggests that
      deviated nose may be a developmental defect caused by a discrepancy in the growth
      of facial bony skeleton between the 2 sides of the face. The objective
      anthropometric measurements developed in this study could be useful for making
      appropriate preoperative facial assessments. LEVEL OF EVIDENCE: NA.

PMID- 25951431
TI  - High IgE levels to alpha-lactalbumin, beta-lactoglobulin and casein predict less
      successful cow's milk oral immunotherapy.
AB  - BACKGROUND: A new treatment option for persistent cow's milk allergy (CMA) is
      oral immunotherapy (OIT). Not all patients develop tolerance during therapy, and
      markers to identify those who will benefit from it are needed. The objective was
      to study the IgE and IgG4 antibody profiles to milk and milk proteins before and
      after OIT in relation to clinical outcome. METHODS: Seventy-six children (5-17
      years) with challenge-verified CMA were subjected to a 6-month OIT protocol. The
      treatment aimed at reaching a maintenance dose of 200 ml CM (high dose = HD).
      Those who did not reach target were analysed as a low-dose (LD) group. Sera were
      characterized before and after OIT regarding serum levels of IgE and IgG4 to milk
      and five milk allergen components evaluated together with clinical CMA symptoms
      and outcome of OIT. RESULTS: Fifty-five (72%) patients reached the maintenance
      dose (HD) during therapy. High specific IgE levels towards the milk allergens
      alpha-lactalbumin (P = 0.048), beta-lactoglobulin (P = 0.006) and casein (P =
      0.015) before OIT start were associated with lower maintenance dose reached.
      Patients who developed desensitization had a larger increase in IgG4 levels to
      alpha-lactalbumin (P = 0.034), beta-lactoglobulin (P = 0.010), casein (P = 0.047)
      and lactoferrin (P = 0.030) during treatment than those who failed. CONCLUSIONS:
      Component-resolved diagnostics before OIT can help to identify children with
      lower probability of a successful OIT outcome, as high IgE levels to alpha
      lactalbumin, beta-lactoglobulin and casein are associated with lower maintenance
      dose reached. An increase in the IgG4 concentration to milk components during
      treatment indicated effective desensitization.

PMID- 25951432
TI  - Antimicrobial nano-silver non-woven polyethylene terephthalate fabric via an
      atmospheric pressure plasma deposition process.
AB  - An antimicrobial nano-silver non-woven polyethylene terephthalate (PET) fabric
      has been prepared in a three step process. The fabrics were first pretreated by
      depositing a layer of organosilicon thin film using an atmospheric pressure
      plasma system, then silver nano-particles (AgNPs) were incorporated into the
      fabrics by a dipping-dry process, and finally the nano-particles were covered by
      a second organosilicon layer of 10-50 nm, which acts as a barrier layer.
      Different surface characterization techniques like SEM and XPS have been
      implemented to study the morphology and the chemical composition of the nano
      silver fabrics. Based on these techniques, a uniform immobilization of AgNPs in
      the PET matrix has been observed. The antimicrobial activity of the treated
      fabrics has also been tested using P. aeruginosa, S. aureus and C. albicans. It
      reveals that the thickness of the barrier layer has a strong effect on the
      bacterial reduction of the fabrics. The durability and stability of the AgNPs on
      the fabrics has also been investigated in a washing process. By doing so, it is
      confirmed that the barrier layer can effectively prevent the release of AgNPs and
      that the thickness of the barrier layer is an important parameter to control the
      silver ions release. 

PMID- 25951433
TI  - Copper-catalyzed aerobic oxidative C-C bond cleavage of unstrained ketones with
      air and amines.
AB  - A unique copper-catalyzed aerobic oxidative C-C bond cleavage of simple
      unstrained ketones with air and amines has been developed. In this chemistry,
      amides and oxo amides are easily synthesized through the selective C-C bond
      cleavage of simple ketones or unstrained cycloketones. The broad substrate scopes
      and use of an inexpensive copper catalyst and green molecular oxygen as an
      oxidant as well as an O-source make this protocol very attractive for potential
      synthetic applications. The control experiments reveal that the present copper
      catalyzed oxidative C-C bond cleavage of simple ketones proceeds in a novel
      catalytic pathway rather than through the cleavage of a dioxetane intermediate. 

PMID- 25951434
TI  - Search for factors affecting antibacterial activity and toxicity of 1,2,4
      triazole-ciprofloxacin hybrids.
AB  - A series of 1,2,4-triazole-based compounds was designed as potential
      antibacterial agents using molecular hybridization approach. The target compounds
      (23-44) were synthesized by Mannich reaction of 1,2,4-triazole-3-thione
      derivatives with ciprofloxacin (CPX) and formaldehyde. Their potent antibacterial
      effect on Gram-positive bacteria was accompanied by similarly strong activity
      against Gram-negative strains. The toxicity of the CPX-triazole hybrids for
      bacterial cells was even up to 18930 times higher than the toxicity for human
      cells. The results of enzymatic studies showed that the antibacterial activity of
      the CPX-triazole hybrids is not dependent solely on the degree of their affinity
      to DNA gyrase and topoisomerase IV. 

PMID- 25951435
TI  - Ultrathin Spinel-Structured Nanosheets Rich in Oxygen Deficiencies for Enhanced
      Electrocatalytic Water Oxidation.
AB  - Electrochemical water splitting is a clean technology for H2 fuels, but greatly
      hindered by the slow kinetics of the oxygen evolution reaction (OER). Herein, a
      series of spinel-structured nanosheets with oxygen deficiencies and ultrathin
      thicknesses were designed to increase the reactivity and the number of active
      sites of the catalysts, which were then taken as an excellent platform for
      promoting the water oxidation process. Theoretical investigations showed that the
      oxygen vacancies confined in the ultrathin nanosheet could lower the adsorption
      energy of H2O, leading to increased OER efficiency. As expected, the NiCo2O4
      ultrathin nanosheets rich in oxygen vacancies exhibited a large current density
      of 285 mA cm(-2) at 0.8 V and a small overpotential of 0.32 V, both of which are
      superior to the corresponding values of bulk samples or samples with few oxygen
      deficiencies and even higher than those of most reported non-precious-metal
      catalysts. This work should provide a new pathway for the design of advanced OER
      catalysts.

PMID- 25951436
TI  - Genome-wide signature of local adaptation linked to variable CpG methylation in
      oak populations.
AB  - It has long been known that adaptive evolution can occur through genetic
      mutations in DNA sequence, but it is unclear whether adaptive evolution can occur
      through analogous epigenetic mechanisms, such as through DNA methylation. If
      epigenetic variation contributes directly to evolution, species under threat of
      disease, invasive competition, climate change or other stresses would have
      greater stores of variation from which to draw. We looked for evidence of natural
      selection acting on variably methylated DNA sites using population genomic
      analysis across three climatologically distinct populations of valley oaks. We
      found patterns of genetic and epigenetic differentiations that indicate local
      adaptation is operating on large portions of the oak genome. While CHG methyl
      polymorphisms are not playing a significant role and would make poor targets for
      natural selection, our findings suggest that CpG methyl polymorphisms as a whole
      are involved in local adaptation, either directly or through linkage to regions
      under selection. 

PMID- 25951437
TI  - Enhanced Protein Production in Escherichia coli by Optimization of Cloning Scars
      at the Vector-Coding Sequence Junction.
AB  - Protein production in Escherichia coli is a fundamental activity for a large
      fraction of academic, pharmaceutical, and industrial research laboratories.
      Maximum production is usually sought, as this reduces costs and facilitates
      downstream purification steps. Frustratingly, many coding sequences are poorly
      expressed even when they are codon-optimized and expressed from vectors with
      powerful genetic elements. In this study, we show that poor expression can be
      caused by certain nucleotide sequences (e.g., cloning scars) at the junction
      between the vector and the coding sequence. Since these sequences lie between the
      Shine-Dalgarno sequence and the start codon, they are an integral part of the
      translation initiation region. To identify the most optimal sequences, we devised
      a simple and inexpensive PCR-based step that generates sequence variants at the
      vector-coding sequence junction. These sequence variants modulated expression by
      up to 1000-fold. FACS-seq analyses indicated that low GC content and relaxed mRNA
      stability (DeltaG) in this region were important, but not the only, determinants
      for high expression. 

PMID- 25951438
TI  - Huge electro-/photo-/acidoinduced second-order nonlinear contrasts from
      multiaddressable indolinooxazolodine.
AB  - In this work, linear and nonlinear optical properties of electro-/acido
      /photoswitchable indolino[2,1-b]oxazolidine derivatives were investigated. The
      linear optical properties of the closed and open forms have been characterized by
      UV-visible and IR spectroscopies associated with DFT calculations. Nonlinear
      optical properties of the compounds have been obtained by ex situ and in situ
      hyper-Rayleigh experiments in solution. We show that protonated, oxidized, and
      irradiated open forms exhibit the same visible absorption and NLO features. In
      particular, the closed and open forms exhibit a huge contrast of the first
      hyperpolarizability with an enhancement factor of 40-45. Additionally, we have
      designed an original electrochemical cell that allows to monitor in situ the
      hyper-Rayleigh response upon electrical stimulus. We report notably a partial but
      good and reversible NLO contrast in situ during oxidation/reduction cycles.
      Thereby, indolinooxazolidine moieties are versatile trimodal switchable units
      which are very promising for applications in devices. 

PMID- 25951439
TI  - Structure-based discovery of the first non-covalent inhibitors of Leishmania
      major tryparedoxin peroxidase by high throughput docking.
AB  - Leishmaniasis is a neglected vector-born disease caused by a protozoan of the
      genus Leishmania and affecting more than 1.300.000 people worldwide. The couple
      tryparedoxin/tryparedoxin peroxidase is essential for parasite survival in the
      host since it neutralizes the hydrogen peroxide produced by macrophages during
      the infection. Herein we report a study aimed at discovering the first class of
      compounds able to non-covalently inhibit tryparedoxin peroxidase. We have solved
      the high-resolution structure of Tryparedoxin peroxidase I from Leishmania major
      (LmTXNPx) in the reduced state and in fully folded conformation. A first series
      of compounds able to inhibit LmTXNPx was identified by means of the high
      throughput docking technique. The inhibitory activity of these compounds was
      validated by a Horseradish peroxidase-based enzymatic assay and their affinity
      for LmTXNPx calculated by surface plasmon resonance experiments. On the basis of
      these results, the analysis of the enzyme-inhibitor docked models allowed us to
      rationally design and synthesize a series of N,N-disubstituted 3-aminomethyl
      quinolones. These compounds showed an inhibitory potency against LmTXNPx in the
      micromolar range. Among them, compound 12 represents the first non-covalent
      LmTXNPx inhibitor reported to date and could pave the way to the discovery of a
      new class of drugs against leishmaniasis. 

PMID- 25951441
TI  - Computational Study of Monosubstituted Azo(tetrazolepentazolium)-Based Ionic
      Dimers.
AB  - The structures of monosubstituted azo(tetrazolepentazolium) cations (N11CHR(+)),
      oxygen-rich anions such as N(NO2)2(-), NO3(-), and ClO4(-), and the corresponding
      ion pairs are investigated using ab initio quantum chemistry calculations. The
      substituents (R) used are H, F, CH3, CN, NH2, OH, OCH3, N3, NF2, and C2H3. The
      stability of the protonated cation is explored by examining the decomposition
      pathway of the protonated cation (N11CH2(+)) to yield molecular N2 fragments. The
      heats of formation of these cations, which are based on isodesmic (bond type
      conserving) reactions, are dependent on the nature of the substituents. Ionic
      dimer structures are obtained, but side reactions including proton transfer,
      binding, and hydrogen bonding are observed in the gas phase. Implicit solvation
      studies are performed to determine the solution properties of the ion pairs. 

PMID- 25951443
TI  - [Editor's Comment].

PMID- 25951444
TI  - [Sialendoscopy].

PMID- 25951442
TI  - Staphylococcus aureus Survives with a Minimal Peptidoglycan Synthesis Machine but
      Sacrifices Virulence and Antibiotic Resistance.
AB  - Many important cellular processes are performed by molecular machines, composed
      of multiple proteins that physically interact to execute biological functions. An
      example is the bacterial peptidoglycan (PG) synthesis machine, responsible for
      the synthesis of the main component of the cell wall and the target of many
      contemporary antibiotics. One approach for the identification of essential
      components of a cellular machine involves the determination of its minimal
      protein composition. Staphylococcus aureus is a Gram-positive pathogen, renowned
      for its resistance to many commonly used antibiotics and prevalence in hospitals.
      Its genome encodes a low number of proteins with PG synthesis activity (9
      proteins), when compared to other model organisms, and is therefore a good model
      for the study of a minimal PG synthesis machine. We deleted seven of the nine
      genes encoding PG synthesis enzymes from the S. aureus genome without affecting
      normal growth or cell morphology, generating a strain capable of PG biosynthesis
      catalyzed only by two penicillin-binding proteins, PBP1 and the bi-functional
      PBP2. However, multiple PBPs are important in clinically relevant environments,
      as bacteria with a minimal PG synthesis machinery became highly susceptible to
      cell wall-targeting antibiotics, host lytic enzymes and displayed impaired
      virulence in a Drosophila infection model which is dependent on the presence of
      specific peptidoglycan receptor proteins, namely PGRP-SA. The fact that S. aureus
      can grow and divide with only two active PG synthesizing enzymes shows that most
      of these enzymes are redundant in vitro and identifies the minimal PG synthesis
      machinery of S. aureus. However a complex molecular machine is important in
      environments other than in vitro growth as the expendable PG synthesis enzymes
      play an important role in the pathogenicity and antibiotic resistance of S.
      aureus. 

PMID- 25951445
TI  - [Spindlecell soft tissue tumors of para- and retropharyngeal space: 5 patients,
      review of literature].
AB  - BACKGROUND: The parapharyngeal space (PPR) is poorly accessible to clinical
      investigation due to its complex anatomy. Neoplasms in this area are rare, become
      lately symptomatic and are diagnosed in advanced stages. Multiple entities can be
      differentiated though malignant mesenchymal tumors are uncommon. PATIENTS: We
      describe characteristic course of spindle cell soft tissue tumors in PPR based on
      5 patients: 2 cases of synovial sarkoma (SyS), 2 cases of malignant peripheral
      nerve sheath tumor (MPNST) without neurofibromatosis, 1 case of Ektomesenchymoma
      (EM). RESULTS: Both patients with SyS showed under multimodal therapy with
      surgery, chemotherapy and radiotherapy a rapid tumor progression and early
      pulmonary metastatic disease. The 2 patients with MPNST were free of recurrence
      after tumor resection and in one case after adjuvant radiotherapy. The patient
      with EM showed no recurrence after surgery. CONCLUSION: Since malignant
      mesenchymal tumors of the PPR are unusual and also not have the typical behavior
      of metastatic epithelial neoplasms or malignant lymphoma, the diagnosis may be
      delayed. It is important to think in atypical lesions in PPR of the possibility
      of a soft tissue tumor and to arrange the necessary diagnostic steps. The imaging
      of choice of the PPR is the MRI, a staging adapted to the entity is necessary.
      The histological differentiation by immunohistochemistry and molecular genetics
      is complex, but is a vital to determine the optimal therapy. Diagnosis and
      treatment should take place in a specialized center.

PMID- 25951446
TI  - [A case of invasive sinugene neuroapergillosis in an immunocompetent patient].

PMID- 25951447
TI  - [From the Expert's Office: General Agreement About the Provision of Hearing
      Systems in the Statutory Accident Insurance].

PMID- 25951448
TI  - [Modern Diagnosis and Therapy of the rhinitis allergica].
AB  - The prevalence of allergic diseases is increasing worldwide. The highest increase
      rate is observed in rhinitis allergica. Apart from the anamnesis, the diagnosis
      relies mainly on skin tests, laboratory analyses and if necessary provocation
      tests. Symptomatic and causal therapy with abstention and specific immunotherapy
      are available as therapeutic means. Specific immunotherapy should be aspired as
      the method of choice. It is comprised of subcutane and sublingular immunity
      therapy. Usually native allergens and allergoids are used as therapeutics.
      Recombinant allergens are currently under development. Modern therapy procedures
      involving these drugs consist of year-round or pre- and co-seasonal treatment
      which spans at least 3-4 years. In cases of polyvalent allergy, different types
      of drugs and therapy procedures can be combined. The future of rhinitis allergica
      treatment lies in further development of specific immunotherapy. 

PMID- 25951449
TI  - [Questions for the specialty boards].

PMID- 25951450
TI  - [Support anesthesia, surgery, surgical instrument update, navigation technique -
      3. Computer-assisted surgery].

PMID- 25951452
TI  - Correction: Extending the "social": anthropological contributions to the study of
      viral haemorrhagic fevers.

PMID- 25951453
TI  - A microscopic analysis of the effects of root surface scaling with different
      power parameters of Er,Cr:YSGG laser.
AB  - The aim of this study was to evaluate the effects of different power parameters
      of an Erbium, Cromium: Yttrium, Scandium, Gallium, Garnet laser (Er,Cr:YSGG
      laser) on the morphology, attachment of blood components (ABC), roughness, and
      wear on irradiated root surfaces. Sixty-five incisive bovine teeth were used in
      this study, 35 of which were used for the analysis of root surface morphology and
      ABC. The remaining 30 teeth were used for roughness and root wear analysis. The
      samples were randomly allocated into seven groups: G1: Er,Cr:YSGG laser, 0.5 W;
      G2: Er,Cr:YSGG laser, 1.0 W; G3: Er,Cr:YSGG laser, 1.5 W; G4: Er,Cr:YSGG laser,
      2.0 W; G5: Er,Cr:YSGG laser, 2.5 W; G6: Er,Cr:YSGG laser, 3.0 W; G7: scaling and
      root planning (SRP) with manual curettes. The root surfaces irradiated by
      Er,Cr:YSGG at 1.0 W and scaling with manual curettes presented the highest
      degrees of ABC. The samples irradiated by the Er,Cr:YSGG laser were rougher than
      the samples treated by the manual curette, and increasing the laser power
      parameters caused more root wear and greater roughness on the root surface. The
      Er,Cr:YSGG laser is safe to use for periodontal treatment, but it is not
      appropriate to use irradiation greater than 1.0 W for this purpose.

PMID- 25951451
TI  - Replication Study in a Japanese Population to Evaluate the Association between 10
      SNP Loci, Identified in European Genome-Wide Association Studies, and Type 2
      Diabetes.
AB  - AIM: We performed a replication study in a Japanese population to evaluate the
      association between type 2 diabetes and 7 susceptibility loci originally
      identified by European genome-wide association study (GWAS) in 2012: ZMIZ1,
      KLHDC5, TLE1, ANKRD55, CILP2, MC4R, and BCAR1. We also examined the association
      of 3 additional loci: CCND2 and GIPR, identified in sex-differentiated analyses,
      and LAMA1, which was shown to be associated with non-obese European type 2
      diabetes. METHODS: We genotyped 6,972 Japanese participants (4,280 type 2
      diabetes patients and 2,692 controls) for each of the 10 single nucleotide
      polymorphisms (SNPs): rs12571751 in ZMIZ1, rs10842994 near KLHDC5, rs2796441 near
      TLE1, rs459193 near ANKRD55, rs10401969 in CILP2, rs12970134 near MC4R, rs7202877
      near BCAR1, rs11063069 near CCND2, rs8108269 near GIPR, and rs8090011 in LAMA1
      using a multiplex polymerase chain reaction invader assay. The association of
      each SNP locus with the disease was evaluated using a logistic regression
      analysis. RESULTS: All SNPs examined in this study had the same direction of
      effect (odds ratio > 1.0, p = 9.77 * 10(-4), binomial test), as in the original
      reports. Among them, rs12571751 in ZMIZ1 was significantly associated with type 2
      diabetes [p = 0.0041, odds ratio = 1.123, 95% confidence interval 1.037-1.215,
      adjusted for sex, age and body mass index (BMI)], but we did not observe
      significant association of the remaining 9 SNP loci with type 2 diabetes in the
      present Japanese population (p >= 0.005). A genetic risk score, constructed from
      the sum of risk alleles for the 7 SNP loci identified by un-stratified analyses
      in the European GWAS meta-analysis were associated with type 2 diabetes in the
      present Japanese population (p = 2.3 * 10(-4), adjusted for sex, age and BMI).
      CONCLUSIONS: ZMIZ1 locus has a significant effect on conferring susceptibility to
      type 2 diabetes also in the Japanese population.

PMID- 25951455
TI  - Correction: Aspartame sensitivity? A double blind randomised crossover study.

PMID- 25951454
TI  - Gene Ontology and KEGG Pathway Enrichment Analysis of a Drug Target-Based
      Classification System.
AB  - Drug-target interaction (DTI) is a key aspect in pharmaceutical research. With
      the ever-increasing new drug data resources, computational approaches have
      emerged as powerful and labor-saving tools in predicting new DTIs. However, so
      far, most of these predictions have been based on structural similarities rather
      than biological relevance. In this study, we proposed for the first time a "GO
      and KEGG enrichment score" method to represent a certain category of drug
      molecules by further classification and interpretation of the DTI database. A
      benchmark dataset consisting of 2,015 drugs that are assigned to nine categories
      ((1) G protein-coupled receptors, (2) cytokine receptors, (3) nuclear receptors,
      (4) ion channels, (5) transporters, (6) enzymes, (7) protein kinases, (8)
      cellular antigens and (9) pathogens) was constructed by collecting data from
      KEGG. We analyzed each category and each drug for its contribution in GO terms
      and KEGG pathways using the popular feature selection "minimum redundancy maximum
      relevance (mRMR)" method, and key GO terms and KEGG pathways were extracted. Our
      analysis revealed the top enriched GO terms and KEGG pathways of each drug
      category, which were highly enriched in the literature and clinical trials. Our
      results provide for the first time the biological relevance among drugs, targets
      and biological functions, which serves as a new basis for future DTI predictions.

PMID- 25951456
TI  - Enhanced horizontal transfer of antibiotic resistance genes in freshwater
      microcosms induced by an ionic liquid.
AB  - The spread and propagation of antibiotic resistance genes (ARGs) is a worldwide
      public health concern. Ionic liquids (ILs), considered as "environmentally
      friendly" replacements for industrial organic solvents, have been widely applied
      in modern industry. However, few data have been collected regarding the potential
      ecological and environmental risks of ILs, which are important for preparing for
      their potential discharge into the environment. In this paper, the IL 1-butyl-3
      methylimidazolium hexafluorophosphate ([BMIm][PF6]) (0.001-5.0 g/L) was tested
      for its effects on facilitating ARGs horizontal transfer mediated by plasmid RP4
      in freshwater microcosms. In the horizontal transfer microcosms, the transfer
      frequency of plasmid RP4 was significantly enhanced (60-fold higher than
      untreated groups) by the IL [BMIm][PF6] (1.0 g/L). Meanwhile, two strains of
      opportunistic pathogen Acinetobacter spp. and Salmonella spp. were isolated among
      the transconjugants, illustrating plasmid RP4 mediated horizontal transfer of
      ARGs occurred in pathogen. This could increase the risk of ARGs dissemination to
      human pathogens and pose great threat to public health. The cause that [BMIm[PF6]
      enhanced the transfer frequency of plasmid RP4 was proposed by suppressed cell
      membrane barrier and enhanced cell membrane permeability, which was evidenced by
      flow cytometry (FCM). This is the first report that some ILs facilitate
      horizontal transfer of plasmid RP4 which is widely distributed in the environment
      and thus add the adverse effects of the environmental risk of ILs. 

PMID- 25951457
TI  - Drak2 Does Not Regulate TGF-beta Signaling in T Cells.
AB  - Drak2 is a serine/threonine kinase expressed highest in T cells and B cells.
      Drak2-/- mice are resistant to autoimmunity in mouse models of type 1 diabetes
      and multiple sclerosis. Resistance to these diseases occurs, in part, because
      Drak2 is required for the survival of autoreactive T cells that induce disease.
      However, the molecular mechanisms by which Drak2 affects T cell survival and
      autoimmunity are not known. A recent report demonstrated that Drak2 negatively
      regulated transforming growth factor-beta (TGF-beta) signaling in tumor cell
      lines. Thus, increased TGF-beta signaling in the absence of Drak2 may contribute
      to the resistance to autoimmunity in Drak2-/- mice. Therefore, we examined if
      Drak2 functioned as a negative regulator of TGF-beta signaling in T cells, and
      whether the enhanced susceptibility to death of Drak2-/- T cells was due to
      augmented TGF-beta signaling. Using several in vitro assays to test TGF-beta
      signaling and T cell function, we found that activation of Smad2 and Smad3, which
      are downstream of the TGF-beta receptor, was similar between wildtype and Drak2-/
      T cells. Furthermore, TGF-beta-mediated effects on naive T cell proliferation,
      activated CD8+ T cell survival, and regulatory T cell induction was similar
      between wildtype and Drak2-/- T cells. Finally, the increased susceptibility to
      death in the absence of Drak2 was not due to enhanced TGF-beta signaling.
      Together, these data suggest that Drak2 does not function as a negative regulator
      of TGF-beta signaling in primary T cells stimulated in vitro. It is important to
      investigate and discern potential molecular mechanisms by which Drak2 functions
      in order to better understand the etiology of autoimmune diseases, as well as to
      validate the use of Drak2 as a target for therapeutic treatment of these
      diseases. 

PMID- 25951459
TI  - Poly(phosphoester)s: A New Platform for Degradable Polymers.
AB  - Poly(phosphoester)s (PPEs) play an important role in nature. They structure and
      determine life in the form of deoxy- and ribonucleic acid (DNA and RNA), and, as
      pyrophosphates, they store up chemical energy in organisms. Polymer chemistry,
      however, is dominated by the nondegradable polyolefins and degradable
      poly(carboxylic ester)s (PCEs) that are produced on a large scale today. Recent
      studies have illustrated the potential of PPEs for future applications beyond
      flame retardancy, and provided a coherent vision to implement this classic
      biopolymer in modern applications that demand biocompatibility and degradability
      as well as the possibility to adjust the properties to individual needs. 

PMID- 25951458
TI  - Sagittal Abdominal Diameter as a Surrogate Marker of Insulin Resistance in an
      Admixtured Population--Brazilian Metabolic Syndrome Study (BRAMS).
AB  - BACKGROUND: Sagittal abdominal diameter (SAD) has been proposed as a surrogate
      marker of insulin resistance (IR). However, the utilization of SAD requires
      specific validation for each ethnicity. We aimed to investigate the potential use
      of SAD, compared with classical anthropometrical parameters, as a surrogate
      marker of IR and to establish the cutoff values of SAD for screening for IR.
      METHODS: A multicenter population survey on metabolic disorders was conducted. A
      race-admixtured sample of 824 adult women was assessed. The anthropometric
      parameters included: BMI, waist circumference (WC), waist-to-hip ratio and SAD.
      IR was determined by a hyperglycemic clamp and the HOMA-IR index. RESULTS: After
      adjustments for age and total body fat mass, SAD (r = 0.23 and r = -0.70) and BMI
      (r = 0.20 and r = -0.71) were strongly correlated with the IR measured by the
      HOMA-IR index and the clamp, respectively (p < 0.001). In the ROC analysis, the
      optimal cutoff for SAD in women was 21.0 cm. The women with an increased SAD
      presented 3.2 (CI 95%: 2.1-5.0) more likelihood of having IR, assessed by the
      HOMA-IR index compared with those with normal SAD (p < 0.001); whereas women with
      elevated BMI and WC were 2.1 (95% CI: 1.4-3.3) and 2.8 (95% CI: 1.7-4.5) more
      likely to have IR (p < 0.001), respectively. No statistically significant results
      were found for waist-to-hip ratio. CONCLUSIONS: SAD can be a suitable surrogate
      marker of IR. Understanding and applying routine and simplified methods is
      essential because IR is associated with an increased risk of obesity-related
      diseases even in the presence of normal weight, slight overweight, as well as in
      obesity. Further prospective analysis will need to verify SAD as a determinant of
      clinical outcomes, such as type 2 diabetes and cardiovascular events, in the
      Brazilian population.

PMID- 25951461
TI  - Management of cervical intraepithelial neoplasia during pregnancy: a simplified
      and cost-effective approach.
AB  - OBJECTIVES: To determine the cost-effectiveness of managing an abnormal
      Papanicolaou (PAP) smear during pregnancy with a single colposcopic exam and
      biopsies, followed by Pap smears in each subsequent trimester of pregnancy and 8
      weeks postpartum. MATERIALS AND METHODS: We reviewed 84 pregnant women with
      cervical intraepithelial neoplasia (CIN) between 1983 and 1991, testing the
      accuracy of an initial biopsy and subsequent Pap smears, to follow the
      progression (or regression) of disease as determined by postpartum biopsy or Pap
      smears. RESULTS: In 26 women with CIN1, 2 (8%) progressed to CIN3. In 29 women
      with CIN2, 5 (17%) progressed to CIN3. Of 29 patients with CIN3, 20 (69%)
      remained at CIN3 and 2 (6%) progressed to microinvasive carcinoma postpartum,
      confirmed by conization. No invasive carcinoma was missed. The cost of colposcopy
      with biopsies and Pap smear is $304, whereas cost of a Pap smear only is $30.
      CONCLUSIONS: Single colposcopy with biopsies at the beginning of pregnancy and
      Pap smears during subsequent trimesters and postpartum should be adequate follow
      up to prevent progression to invasive cancer and represents a significant cost
      savings.

PMID- 25951462
TI  - Streptococcal vaginosis.
AB  - OBJECTIVE: This study was initiated to discover the etiology and pathogenesis of
      persistent vulvovaginal symptoms after adequate and appropriate therapy for
      bacterial vaginosis. MATERIALS AND METHODS: Included in this study, which spanned
      the period from January 1988 to June 1996, were all patients who were referred by
      their gynecologists for continuing vulvovaginal symptoms after treatment for
      bacterial vaginosis. History, pelvic examination, saline wet-mount and 10%
      potassium hydroxide preparations, and aerobic and anaerobic cultures were
      performed. Several antibiotic regimens were prescribed, and results were
      tabulated. Patients were considered to be cured when asymptomatic, when the
      saline wet-mount preparation showed lactobacillus-dominant flora, and when
      cultures were reported as normal or mixed vaginal flora. RESULTS: Twenty-four
      patients were recruited for this study. These patients had been treated for a
      total of 554 months prior to their referral for vulvovaginal consultation. After
      saline wet-mount examination, 90% had no lactobacilli and showed an abundance of
      coccal bacterial forms. Twenty-six cultures were performed, of which 92% were
      positive for streptococci. Group B streptococci were reported in 71%, group D in
      29%, and group A in none. The most successful therapy was amoxicillin, 500 mg
      three times daily for 10 days. Treatment for 7 days was inadequate. CONCLUSIONS:
      Overgrowth of streptococci after appropriate therapy for bacterial vaginosis
      produces continuing vulvovaginal symptoms. Amoxicillin, 500 mg three times daily
      for 10 days, returns lactobacillus-dominated flora and an asymptomatic patient in
      a majority of cases.

PMID- 25951460
TI  - A novel quantitative hemolytic assay coupled with restriction fragment length
      polymorphisms analysis enabled early diagnosis of atypical hemolytic uremic
      syndrome and identified unique predisposing mutations in Japan.
AB  - For thrombotic microangiopathies (TMAs), the diagnosis of atypical hemolytic
      uremic syndrome (aHUS) is made by ruling out Shiga toxin-producing Escherichia
      coli (STEC)-associated HUS and ADAMTS13 activity-deficient thrombotic
      thrombocytopenic purpura (TTP), often using the exclusion criteria for secondary
      TMAs. Nowadays, assays for ADAMTS13 activity and evaluation for STEC infection
      can be performed within a few hours. However, a confident diagnosis of aHUS often
      requires comprehensive gene analysis of the alternative complement activation
      pathway, which usually takes at least several weeks. However, predisposing
      genetic abnormalities are only identified in approximately 70% of aHUS. To
      facilitate the diagnosis of complement-mediated aHUS, we describe a quantitative
      hemolytic assay using sheep red blood cells (RBCs) and human citrated plasma,
      spiked with or without a novel inhibitory anti-complement factor H (CFH)
      monoclonal antibody. Among 45 aHUS patients in Japan, 24% (11/45) had moderate-to
      severe (>=50%) hemolysis, whereas the remaining 76% (34/45) patients had mild or
      no hemolysis (<50%). The former group is largely attributed to CFH-related
      abnormalities, and the latter group has C3-p.I1157T mutations (16/34), which were
      identified by restriction fragment length polymorphism (RFLP) analysis. Thus, a
      quantitative hemolytic assay coupled with RFLP analysis enabled the early
      diagnosis of complement-mediated aHUS in 60% (27/45) of patients in Japan within
      a week of presentation. We hypothesize that this novel quantitative hemolytic
      assay would be more useful in a Caucasian population, who may have a higher
      proportion of CFH mutations than Japanese patients. 

PMID- 25951463
TI  - "Rapid-Onset" Cervical Cancer due to Failures in a Screening Program.
AB  - Cervical cancer is considered a preventable disease because, in its preinvasive
      form, it can be detected by a Papanicolaou (Pap) smear and effectively eradicated
      by local therapy. The fact that new cases of invasive cancers are reported even
      in "well-organized" screening programs has been blamed on the so-called rapid
      onset cancers. This assumption led to resistance in the medical community to
      accept a 3-year interval between Pap smear tests. Rapid-onset cervical cancer has
      been defined as cancer diagnosed within 3 years of a normal Pap smear. Because
      nearly 30% of patients in whom cervical cancer is diagnosed never had a Pap smear
      and another 30% did not follow the recommendation to be tested at least every 3
      years, we could theorize that the other 40%, who had a normal-appearing
      cytological workup in the last 3 years, have a rapidly occurring cancer. However,
      a review of the reasons for screening failure in those patients reveals that
      inadequate and false-negative smears and failure to investigate an abnormal test
      account for more than 95% of so-called rapid-onset cervical cancers. Therefore,
      if eradication of cervical cancer is to be accomplished in the twenty-first
      century, countries will have to develop an organized comprehensive screening
      program that includes (1) recruitment planning to extend screening to all
      eligible women, (2) a recall system for investigation and management of
      abnormalities, (3) quality assurance for cytology and colposcopy, and (4) quality
      control of the program. 

PMID- 25951464
TI  - Screening for cervical carcinoma in developmentally disabled women in residential
      facilities.
AB  - OBJECTIVE: Our aim was to describe the results of Papanicolaou (Pap) smears
      obtained during routine pelvic examinations on virginal developmentally disabled
      women and to compare the incidence rate of abnormal cervical cytology to the
      general population. MATERIALS AND METHODS: This study was descriptive and
      comparative. Subjects were a convenience sample of 230 developmentally disabled
      virginal women (mean age, 31 +/- 9.6 years) who were living in a state-operated
      residential facility and had screening pelvic examinations and Pap smears.
      Cytological diagnoses were compared with a general population (n = 92, 151).
      RESULTS: Overall rate of abnormal Pap smears was significantly lower than the age
      adjusted rate in the general population (z = 2.88, p <.01). All subsequent
      cytology in the study population reverted to normal. No evidence of cervical
      neoplasia was seen in the study population. CONCLUSIONS: Routine screening for
      cervical carcinoma is not indicated for this population of developmentally
      disabled women who have not had sexual inter-course.

PMID- 25951465
TI  - Conservative management of cervical intraepithelial neoplasia 3 during pregnancy:
      is conization ever indicated?
AB  - During an 8-year period, 200 patients with biopsy-proved cervical intraepithelial
      neoplasia grade 3 (CIN3) of the cervix were evaluated serially both before and
      after birth with serial Cytobrush cytology, colposcopy, and biopsy. No patient
      underwent cervical conization, regardless of cytological or colposcopic findings.
      Ninety percent of patients had postpartum CIN3, 5% had CIN1, and 4.5% showed no
      evidence of dysplasia. One patient was found to have a stage IA2 invasive
      squamous cell carcinoma of the cervix on postpartum conization. CIN3 rarely
      regresses postpartum, but conization may be avoided even in the presence of
      unsatisfactory colposcopy, discrepancy between Papanicolaou smear and biopsy, or
      cytological findings consistent with early invasive cervical cancer. 

PMID- 25951466
TI  - Correlating preoperative cytology and colposcopic biopsy with final histology
      after conization of the cervix.
AB  - OBJECTIVES: We set out to evaluate the predictive value of preoperative cytology
      and colposcopic histology in determining final pathology after conization of the
      cervix in the era of the Bethesda system. METHODS: A retrospective review of the
      charts of 280 patients who had cold-knife conization was undertaken. Preoperative
      cytology and colposcopic biopsy histology were compared to the cone biopsy
      histology. The Spearman's correlation coefficient was used to determine the
      correlation between both preoperative cytology and histology and histology of the
      cone biopsy. RESULTS: Pre-operative cytology matched cone histology in only 56.5%
      of cases and was within one grade in 92.3% of cases, with a correlation of 0.369.
      Most outliers were high-grade cytology not confirmed at cone biopsy. Preoperative
      biopsy correlated even less with cone histology: Exact correlation occurred in
      40% of cases, correlation within one grade was seen in 69.4% of cases, and the
      Spearman correlation coefficient was 0.328. Most outliers were high-grade lesions
      on cone biopsy that were not detected with colposcopic biopsy. CONCLUSIONS: Pre
      operative cytology and histology do not predict final pathology with enough
      accuracy to allow management to be determined by them. Conization of the cervix
      remains a useful procedure in the triage of the abnormal cytological smear.

PMID- 25951467
TI  - Histopathological variables predicting high-grade squamous intraepithelial
      lesions after large-loop excision of the transformation zone.
AB  - OBJECTIVE: Our aim was to determine whether histopathological variables predict
      persistent high-grade squamous intraepithelial lesions (HGSIL) after large-loop
      excision of the transformation zone (LLETZ). MATERIALS AND METHODS: All patients
      with cervical intraepithelial neoplasia (CIN) grade 2 or 3 on a LLETZ specimen
      with at least one follow-up Papanicolaou (Pap) test were identified.
      Histopathological variables were evaluated for the potential to predict HGSIL on
      a follow-up Pap test. Variables examined included endocervical margin status,
      ectocervical margin status, endocervical curettage (ECC) result, presence or
      absence of endocervical glandular involvement, and presence or absence of
      koilocytosis. RESULTS: Two hundred and nineteen cases were identified. A follow
      up Pap test showed HGSIL in 16 patients (7.3%). Of the histopathological
      variables studied, only a positive ECC at the time of LLETZ conization predicted
      HGSIL on follow-up cytology (p =.0002). Endocervical margin status, ectocervical
      margin status, presence or absence of glandular involvement, and presence or
      absence of koilocytosis were not associated significantly with HGSIL at follow
      up. CONCLUSION: Most histopathological factors from LLETZ conization do not
      predict reliably the presence of HGSIL at the time of follow-up Pap test. A
      positive ECC at the time of LLETZ, however, may predict those patients destined
      to have persistence or recurrence. These findings suggest that conservative
      follow-up is warranted after LLETZ conization.

PMID- 25951468
TI  - Cryotherapy of the cervix.
AB  - Cryotherapy is an office-based ablative procedure for treating premalignant
      cervical disease. The procedure may be easily performed and serious complications
      occur rarely. When compared with other types of cervical neoplasia surgical
      therapies, cryotherapy is relatively inexpensive and comparably effective when
      properly conducted. 

PMID- 25951469
TI  - Electronic educational systems and colposcopy.

PMID- 25951470
TI  - Editor and author.

PMID- 25951471
TI  - The american society for colposcopy and cervical pathology.

PMID- 25951472
TI  - COLPOSCOPIC EVALUATION DURING PREGNANCY: What Would You Recommend for Further
      Management?

PMID- 25951473
TI  - Clinical questions: ask the experts, journal of lower genital tract disease 1(3):
      177, 1997.

PMID- 25951474
TI  - From railways to "soup to nuts".

PMID- 25951477
TI  - Effect of Daily Contact Lens Cleaning on Ocular Adverse Events during Extended
      Wear.
AB  - PURPOSE: The purpose of the study was to assess what effect daily cleaning of
      contact lenses with a multipurpose disinfection solution (MPDS), during 30 nights
      extended wear, would have on contact lens-related adverse events. METHODS: This
      was a prospective, open-label, randomized, controlled, parallel-group, 3-month
      clinical study in which 193 participants were dispensed with lotrafilcon A
      silicone hydrogel lenses for a 30-day extended-wear schedule and with lenses
      replaced monthly. Participants were randomized to a control or test group. Test
      subjects were required to remove lenses daily after waking, clean them with the
      MPDS, and reinsert the lenses. Control subjects wore lenses without removal for
      30 days extended wear. Handling-related lens contamination was assessed at the
      baseline visit. RESULTS: There was no significant difference between the test and
      control groups for the incidence of significant corneal infiltrative events (1.3
      vs. 4.9%, p = 0.368), total corneal infiltrative events (2.6 vs. 4.9%, p =
      0.682), or mechanical events (1.3 vs. 2.5%, p = 1.00). The test group had greater
      corneal staining (p < 0.047) and fewer mucin balls (p = 0.033). Handling-related
      lens contamination (unworn lenses) resulted in isolation of Gram-positive
      bacteria from 92.5% of test lenses compared with 87.5% of control lenses (p =
      0.712). Gram-negative bacteria were isolated from 5% of test subjects compared
      with 2.5% of control subjects (p = 1.00). Fungus was isolated from 2.5% of
      subjects in both the test and control groups (p = 1.00). CONCLUSIONS: The
      intervention of daily morning cleaning of the lens surface with an MPDS during
      extended wear did not significantly influence the incidence of adverse events.

PMID- 25951478
TI  - The effect of contact lens hygiene behavior on lens case contamination.
AB  - PURPOSE: To assess the association between the levels of lens case contamination
      and lens wearers' hygiene behaviors. METHODS: Contact lens wearers were surveyed
      for information on wearer demographics and contact lens hygiene behavior.
      Microbial analysis of lens cases was performed. Multivariate analysis was used to
      identify factors associated with contact lens storage case contamination.
      RESULTS: One hundred nineteen contact lens wearers responded. The mean (+/-SD)
      age of the participant was 32 (+/-1) years (range, 18 to 69 years). Seventy
      percent of the participants were female. Sixty-six percent of lens cases were
      contaminated (median, 25; range, 0 to 107 colony-forming units [CFUs]). In the
      multivariate analysis, washing hands with soap and water (1.8 +/- 2.0 log10
      CFU/case) rather than just water or no washing was associated with lower levels
      of lens case contamination (2.4 +/- 2.1 log10 CFU/case; p = 0.005). Lens cases
      received wet had higher levels of contamination than dry cases (1.5 +/- 1.5 vs.
      2.4 +/- 2.5 log10 CFU/case; p = 0.015). Mismatching lens case and disinfecting
      solution was a risk factor for lens case contamination (p = 0.019). Lens wearers
      who had more than 2 years of wearing experience had higher levels of
      contamination than those who had less than 2 years of wearing experience (2.1 +/-
      2.1 vs. 1.1 +/- 1.5 log10 CFU/case; p = 0.04). CONCLUSIONS: Major factors that
      can reduce lens case contamination were washing hands with soap and water, air
      drying lens cases, and matching of the disinfecting solution with lens case
      (i.e., from the same manufacturer). This information is beneficial when advising
      lens wearers in clinical practice.

PMID- 25951479
TI  - Stereoacuity changes after laser in situ keratomileusis.
AB  - PURPOSE: To study changes in near and distance stereoacuity after laser in situ
      keratomileusis (LASIK). METHODS: A prospective interventional study was conducted
      at an apex tertiary care ophthalmology center in India. Near and distance
      stereoacuity was tested in 40 patients (80 eyes) who underwent LASIK for myopic
      correction and got unaided vision of 0.67 or better in each eye. Stereoacuity was
      tested with best spectacle correction before LASIK, and post-LASIK stereoacuity
      was tested with unaided eye near and distance Randot tests. RESULTS: Forty
      patients (80 eyes) had a mean (+/-SD) pre-LASIK refractive error of -4.70 (+/
      1.72) DS OD and -4.59 (+/-1.58) DS OS and a mean (+/-SD) anisometropia of 0.55
      (+/-0.51) DS. The median pre-LASIK near stereoacuity was 70 arcsec and distance
      stereoacuity was 200 arcsec, both of which improved after LASIK to 30 and 60
      arcsec, respectively (p < 0.001, both). Amount of refractive error was not
      associated with stereoacuity but anisometropia of greater than or equal to 1
      diopter had significantly worse distance stereoacuity in both the pre-LASIK and
      post-LASIK period. The post-LASIK near stereoacuity and distance stereoacuity
      were strongly associated (r = 0.706, p < 0.001) unlike the change in
      stereoacuity. CONCLUSIONS: Near and distance stereoacuity shows significant
      improvement after LASIK. Stereoacuity is associated with the degree of
      anisometropia but not the amount of refractive error corrected.

PMID- 25951480
TI  - Random-dot stereopsis in microstrabismic children: stimulus size matters.
AB  - PURPOSE: Although children with microstrabismus demonstrate stereoscopic
      abilities when assessed with clinical tests containing visible contours (local
      stereopsis), severe stereoscopic impairments are reported when using random-dot
      stereogram (RDS). This differential performance may be associated with the
      decreasing interocular correlation resulting from the central suppression present
      in the deviated eye, affecting global stereopsis to a greater extent. METHODS: To
      test this hypothesis, stereoscopic performance on tasks using contour/local
      (experiment 1), RDS depth (experiment 2), and RDS shape discrimination
      (experiment 3) was obtained in nine microstrabismic children and compared with
      that of control participants. For each task, stereoscopic stimuli of 4 and 12
      degrees diameter were used to differentially solicit the contribution of the
      central suppression area. RESULTS: Results demonstrated that performance on the
      local stereopsis task was very similar for both target sizes, measurable for all
      microstrabismic participants, and comparable to that of control subjects. On the
      other hand, global stereoacuity using RDS was not measurable for one-third of the
      microstrabismic participants when small stimuli were used, but stereoperception
      became possible for large stimuli condition in which the interocular correlation
      disruption was presumably negligible. Along these lines, global shape stereopsis
      was found to increase by nearly 50% in the microstrabismic group when large
      targets were used. In all experiments, only coarse stereopsis could be measured
      in microstrabismic children, regardless of the stimulus size. CONCLUSION:
      Although our findings suggest that interocular correlation may play a role in
      deficits of stereopsis in microstrabismus, other altered processes such as
      abnormal experience, retinal correspondence, and high-level coding are likely to
      also be involved.

PMID- 25951481
TI  - Evidence for an eye-movement contribution to normal foveal crowding.
AB  - PURPOSE: Along with contour interaction, inaccurate and imprecise eye movements
      and attention have been suggested to contribute to poorer acuity for "crowded"
      versus uncrowded targets. To investigate the role of eye movements in foveal
      crowding, we compared percent correct letter identification for short and long
      lines of near-threshold letters with different separations. METHODS: Five normal
      observers read short (4 to 6 letters) and long (10 to 12 letters) lines of near
      threshold, Sloan letters with edge-to-edge letter separations of 0.5, 1, and 2
      letter spaces. Percent correct letter identification for the 2 to 4 interior
      letters in short strings and the 8 to 10 interior letters in long strings was
      compared with a no-crowding condition. RESULTS: Letter identification was
      significantly worse than the no-crowding condition for long letter strings with a
      separation of 1 letter space and for both long and short letter strings with a
      separation of 0.5 letter spaces. Observers more often reported the incorrect
      number of letters in long than in short letter strings, even for a separation of
      2 letter spaces. Similar results were obtained during straight-ahead gaze and
      while viewing in 30 to 40 degrees left gaze, where two of the five observers
      exhibited an increase in horizontal fixational instability. CONCLUSIONS: We argue
      that lower percent correct letter identification and more frequent errors in
      reporting the number of letters in long compared with short letter strings
      reflect an eye-movement contribution to foveal crowding.

PMID- 25951484
TI  - Letter to the editor: Changes in macular function after ozurdex for retinal vein
      occlusion.

PMID- 25951485
TI  - Authors' response.

PMID- 25951487
TI  - Celecoxib Inhibits the Lytic Activation of Kaposi's Sarcoma-Associated
      Herpesvirus through Down-Regulation of RTA Expression by Inhibiting the
      Activation of p38 MAPK.
AB  - Kaposi's sarcoma associated herpesvirus (KSHV) is the etiologic agent of Kaposi's
      sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's
      disease (MCD). KSHV's lytic replication cycle is critical for the pathogenesis of
      KSHV-associated diseases. Despite recent progress in the development of
      treatments for KSHV associated malignancies, these therapies are not completely
      efficacious and cause side effects. Therefore, more effective therapies with
      antiviral agents against KSHV are urgently needed. In this study, we identified
      celecoxib as an antiviral agent against KSHV. Our data suggest that celecoxib
      inhibits the lytic activation of KSHV through the down-regulation of the
      expression of the lytic switch protein, replication and transcription activator
      (RTA), by inhibiting the activation of p38 MAPK. Therefore, celecoxib may provide
      a candidate inhibitor for the therapeutic research of KSHV-related malignancies. 

PMID- 25951489
TI  - Increased prevalence of restless legs syndrome in patients with Crohn's disease.
AB  - OBJECTIVE: To determine (a) the incidence of restless legs syndrome (RLS) in
      patients with Crohn's disease (CD), (b) whether and how the occurrence and
      severity of RLS is related to severity of CD, and (c) how RLS influences the
      quality of life of CD patients. BASIC METHODS: We carried out a cross-sectional
      questionnaire study in a random selection of 144 CD patients and 80 controls.
      Differences were calculated using a chi-test (categorical data), an independent T
      test (continuous data, normal distribution), or a Mann-Whitney U-test (continuous
      data, non-normal distribution). Logistic regression analysis was carried out to
      establish the relation between CD and RLS after adjusting for risk factors. MAIN
      RESULTS: The prevalence of RLS was 25.7% (37/144) in CD patients compared with
      12.5% (10/80) in the control group (P=0.02). CD patients using caffeine and
      patients with arthralgias had a higher risk for RLS. A higher score on the
      modified Harvey Bradshaw Index and CD-related surgery were also associated with a
      higher risk for RLS. CD-related surgery was also associated with a more severe
      course of RLS. Patients and controls with RLS had a lower score on 'physical
      functioning', one of the subcategories of the RAND-36 quality-of-life
      questionnaire. PRINCIPAL CONCLUSION: RLS occurs more frequently in patients with
      CD compared with healthy individuals. A more severe course of CD seems to be
      associated with a higher risk for RLS. The presence of RLS has a negative
      influence on quality of life, mainly interfering with physical activities of
      daily life.

PMID- 25951488
TI  - Intracellular Trafficking of Baculovirus Particles: A Quantitative Study of the
      HearNPV/HzAM1 Cell and AcMNPV/Sf9 Cell Systems.
AB  - To replace the in vivo production of baculovirus-based biopesticides with a more
      convenient in vitro produced product, the limitations imposed by in vitro
      production have to be solved. One of the main problems is the low titer of
      HearNPV budded virions (BV) in vitro as the use of low BV titer stocks can result
      in non-homogenous infections resulting in multiple virus replication cycles
      during scale up that leads to low Occlusion Body yields. Here we investigate the
      baculovirus traffic in subcellular fractions of host cells throughout infection
      with an emphasis on AcMNPV/Sf9 and HearNPV/HzAM1 systems distinguished as "good"
      and "bad" BV producers, respectively. qPCR quantification of viral DNA in the
      nucleus, cytoplasm and extracellular fractions demonstrated that although the
      HearNPV/HzAM1 system produces twice the amount of vDNA as the AcMNPV/Sf9 system,
      its percentage of BV to total progeny vDNA was lower. vDNA egress from the
      nucleus to the cytoplasm is sufficient in both systems, however, a higher
      percentage of vDNA in the HearNPV/HzAM1 system remain in the cytoplasm and do not
      bud out of the cells compared to the AcMNPV/Sf9 system. In both systems more than
      75% of the vDNA produced in the nuclear fraction go unused, without budding or
      being encapsulated in OBs showing the capacity for improvements that could result
      from the engineering of the virus/cell line systems to achieve better
      productivities for both BV and OB yields.

PMID- 25951490
TI  - Risk factors for band-induced ulcer bleeding after prophylactic and therapeutic
      endoscopic variceal band ligation.
AB  - BACKGROUND AND AIMS: Endoscopic variceal band ligation (EVBL) aims to eradicate
      high-risk oesophageal varices. There is a small risk of precipitating bleeding
      from EVBL-induced oesophageal ulceration, which is associated with significant
      mortality. We explore the risk factors and outcome of EVBL-induced ulcer
      bleeding. METHODS: Retrospective review of our endoscopy database between 2007
      and 2012 identified upper endoscopies during which EVBL was performed. Patient
      demographics, biochemistry and endoscopic findings were recorded as were the
      complications of EVBL-induced ulcer bleeding and death. RESULTS: A total of 749
      episodes of EVBL were performed in 347 patients with a mean Model for End-stage
      Liver Disease (MELD) score of 15.8. In all, 609 procedures were performed for
      prophylaxis and 140 for acute haemorrhage. There were 21 episodes (2.8% of
      procedures) of EVBL-induced ulcer bleeding in 18 patients, five of whom
      subsequently died (28%). On multivariable analysis, acute variceal haemorrhage
      was the only significant predictor of EVBL-induced ulcer bleeding [odds ratio
      (OR) 6.25 (2.57-15.14), P<0.0001]. In 609 procedures performed for prophylaxis,
      the EVBL-induced ulcer bleeding rate was 1.5%, with 22% mortality. In this group,
      higher MELD score and reflux oesophagitis were associated significantly with EVBL
      induced ulcer bleeding [OR 25.53 (2.14-303.26), P=0.010 and OR 1.07 (1.01-1.13),
      P=0.019, respectively]. CONCLUSION: Our EVBL-induced ulcer bleeding rate was low,
      but associated with significant mortality. Highest rates were observed following
      EVBL for acute variceal haemorrhage, for which EVBL is unavoidable. The incidence
      was lower following prophylactic EVBL, with the MELD score being the predominant
      risk factor. Reflux oesophagitis requires further investigation as a potentially
      modifiable risk factor for EVBL-induced ulcer bleeding.

PMID- 25951491
TI  - The PAPAS index: a novel index for the prediction of hepatitis C-related
      fibrosis.
AB  - BACKGROUND: Several noninvasive tests have been developed to determine the degree
      of hepatic fibrosis in patients with chronic hepatitis C (CHC) without performing
      liver biopsy. AIM: This study aimed to determine the performance of the PAPAS
      (Platelet/Age/Phosphatase/AFP/AST) index in patients with CHC for the prediction
      of significant fibrosis and cirrhosis and to compare it with other noninvasive
      tests. To date, no study has evaluated the application of the PAPAS index in CHC
      associated liver fibrosis. MATERIALS AND METHODS: This retrospective study
      included 137 consecutive patients with CHC who had undergone a percutaneous liver
      biopsy before treatment. The aspartate aminotransferase/platelet ratio (APRI),
      aspartate aminotransferase/alanine transaminase ratio (AAR), age-platelet index
      (API), FIB4, cirrhosis discriminate score (CDS), the Goteborg University
      cirrhosis index (GUCI), and PAPAS were calculated and compared with the
      diagnostic accuracies of all fibrosis indices between the groups F0-F2 (no-mild
      fibrosis) versus F3-F6 (significant fibrosis) and F0-F4 (no cirrhosis) versus F5
      F6 (cirrhosis). RESULTS: To predict significant fibrosis, the area under curve
      (95% confidence interval) for FIB4 was 0.727 followed by GUCI (0.721),
      PAPAS~APRI~CDS (0.716), and API (0.68). To predict cirrhosis, the area under
      curve (95% confidence interval) for FIB4 was calculated to be 0.735, followed by
      GUCI (0.723), PAPAS~APRI~CDS~(0.71), and API (0.66). No statistically significant
      difference was observed among these predictors to exclude both significant
      fibrosis and cirrhosis (P>0.05). CONCLUSION: The diagnostic capability of the
      PAPAS index has moderate efficiency and was not superior to other fibrosis
      markers for the identification of fibrosis in CHC patients. There is a need for
      more comprehensive prospective studies to help determine the diagnostic value of
      PAPAS for liver fibrosis.

PMID- 25951492
TI  - Thin and thick layers of resin-based sealer cement bonded to root dentine
      compared: Adhesive behaviour.
AB  - This study aims to evaluate tensile and shear bond strengths of one epoxy (AH)
      and two methacrylate resin-based sealers (EZ and RS) in thin and thick layers
      bonded to root dentine. An alignment device was prepared for accurate positioning
      of 20 root dentine cylinders in a predefined gap of 0.1 or 1 mm. Sealer was
      placed in the interface. Bond strength tests were conducted. Mode of failures and
      representative surfaces were evaluated. Data were analysed using anova and post
      hoc tests, with P < 0.05. The thick layer of sealer produced higher bond
      strength, except for the shear bond strength of EZ. Significant differences
      between thin and thick layers were found only in tensile bond strengths of AH and
      RS. Mixed type of failure was constantly found with all sealers. Bond strengths
      of thick layers of resin-based sealers to root dentine tended to be higher than
      with thin layers. 

PMID- 25951493
TI  - Growth hormone in adipose dysfunction and senescence.

PMID- 25951494
TI  - An effective visualization technique for depth perception in augmented reality
      based surgical navigation.
AB  - BACKGROUND: Depth perception is a major issue in augmented reality (AR)-based
      surgical navigation. We propose an AR and virtual reality (VR) switchable
      visualization system with distance information, and evaluate its performance in a
      surgical navigation set-up. METHODS: To improve depth perception, seamless
      switching from AR to VR was implemented. In addition, the minimum distance
      between the tip of the surgical tool and the nearest organ was provided in real
      time. To evaluate the proposed techniques, five physicians and 20 non-medical
      volunteers participated in experiments. RESULTS: Targeting error, time taken, and
      numbers of collisions were measured in simulation experiments. There was a
      statistically significant difference between a simple AR technique and the
      proposed technique. CONCLUSIONS: We confirmed that depth perception in AR could
      be improved by the proposed seamless switching between AR and VR, and providing
      an indication of the minimum distance also facilitated the surgical tasks.

PMID- 25951495
TI  - Selective depletion of tumor neovasculature by microbubble destruction with
      appropriate ultrasound pressure.
AB  - Low-intensity ultrasound-microbubble (LIUS-MB) treatment is a promising
      antivascular therapy for tumors. We sought to determine whether LIUS-MB treatment
      with an appropriate ultrasound pressure could achieve substantial and persistent
      cessation of tumor perfusion without having significant effects on normal tissue.
      Further, we investigated the mechanisms underlying this treatment. Murine S-180
      sarcomas, thigh muscles, and skin tissue from 60 tumor-bearing mice were
      subjected to sham therapy, an ultrasound application combined with microbubbles
      in four different ultrasound pressures (0.5, 1.5, 3.0, 5.0 MPa), or ultrasound at
      5.0 MPa alone. Subsequently, contrast-enhanced ultrasonic imaging and
      histological studies were performed. Tumor microvessels, tumor cell necrosis,
      apoptosis, tumor growth, and survival were evaluated in 85 mice after treatment
      with the selected ultrasound pressure. We found that twenty-four hours after LIUS
      MB treatment at 3.0 MPa, blood perfusion and microvessel density of the tumor had
      substantially decreased by 84 +/- 8% and 84%, respectively (p < 0.01). Similar
      reductions were not observed in the muscle or skin. Additionally, an extreme
      reduction in the number of immature vessels was observed in the tumor (reduced by
      90%, p < 0.01), while the decrease in mature vessels was not significant.
      Further, LIUS-MB treatment at 3.0 MPa promoted tumor cell necrosis and apoptosis,
      delayed tumor growth, and increased the survival rate of tumor-bearing mice (p <
      0.01). These findings indicate that LIUS-MB treatment with an appropriate
      ultrasound pressure could selectively and persistently reduce tumor perfusion by
      depleting the neovasculature. Therefore, LIUS-MB treatment offers great promise
      for clinical applications in antivascular therapy for solid tumors.

PMID- 25951496
TI  - Isolation and characterisation of cDNA encoding a wheat heavy metal-associated
      isoprenylated protein involved in stress responses.
AB  - In cells, metallochaperones are important proteins that safely transport metal
      ions. Heavy metal-associated isoprenylated plant proteins (HIPPs) are
      metallochaperones that contain a metal binding domain and a CaaX isoprenylation
      motif at the carboxy-terminal end. To investigate the roles of wheat heavy metal
      associated isoprenylated plant protein (TaHIPP) genes in plant development and in
      stress responses, we isolated cDNA encoding the wheat TaHIPP1 gene, which
      contains a heavy metal-associated domain, nuclear localisation signals and an
      isoprenylation motif (CaaX motif). Quantitative real-time PCR analysis indicated
      that the TaHIPP1 gene was differentially expressed under biotic and abiotic
      stresses. Specifically, TaHIPP1 expression was up-regulated by ABA exposure or
      wounding. Additionally, TaHIPP1 over-expression in yeast (Schizosaccharomyces
      pombe) significantly increased the cell growth rate under Cu(2+) and high
      salinity stresses. The nuclear localisation of the protein was confirmed with
      confocal laser scanning microscopy of epidermal onion cells after particle
      bombardment with chimeric TaHIPP1-GFP constructs. In addition, TaHIPP1 was shown
      to enhance the susceptibility of wheat to Pst as determined by virus-induced gene
      silencing. These data indicate that TaHIPP1 is an important component in defence
      signalling pathways and may play a crucial role in the defence response of wheat
      to biotic and certain abiotic stresses. 

PMID- 25951497
TI  - miRNA profiling in vitreous humor, vitreal exosomes and serum from uveal melanoma
      patients: Pathological and diagnostic implications.
AB  - Uveal melanoma (UM) represents approximately 5-6% of all melanoma diagnoses and
      up to 50% of patients succumb to their disease. Although several methods are
      available, accurate diagnosis is not always easily feasible because of potential
      accidents (e.g., intraocular hemorrhage). Based on the assumption that the
      profile of circulating miRNAs is often altered in human cancers, we verified
      whether UM patients showed different vitreous humor (VH) or serum miRNA profiles
      with respect to healthy controls. By using TaqMan Low Density Arrays, we analyzed
      754 miRNAs from VH, vitreal exosomes, and serum of 6 UM patients and 6 healthy
      donors: our data demonstrated that the UM VH profile was unique and only
      partially overlapping with that from serum of the same patients. Whereas, 90% of
      miRNAs were shared between VH and vitreal exosomes, and their alterations in UM
      were statistically overlapped with those of VH and vitreal exosomes, suggesting
      that VH alterations could result from exosomal dysregulation. We report 32 miRNAs
      differentially expressed in UM patients in at least 2 different types of samples
      analyzed. We validated these data on an independent cohort of 12 UM patients.
      Most alterations were common to VH and vitreal exosomes (e.g., upregulation of
      miR-21,-34 a,-146a). Interestingly, miR-146a was upregulated in the serum of UM
      patients, as well as in serum exosomes. Upregulation of miR-21 and miR-146a was
      also detected in formalin-fixed, paraffin-embedded UM, suggesting that VH or
      serum alterations in UM could be the consequence of disregulation arising from
      tumoral cells. Our findings suggest the possibility to detect in VH and serum of
      UM patients "diagnostic" miRNAs released by the affected eye: based on this, miR
      146a could be considered a potential circulating marker of UM. 

PMID- 25951498
TI  - Coronary artery calcification and large artery stiffness in renal transplant
      recipients.
AB  - PURPOSE: Coronary artery calcification (CAC) is an independent predictor of
      cardiovascular (CV) events in renal transplant recipients (RTR). Carotid-femoral
      pulse wave velocity (PWV), a non-invasive measure of large artery stiffness, also
      predicts CV events in RTR. The study investigated the relationship between CAC
      and PWV in RTR and assessed the performance of PWV measurement in predicting CAC.
      PATIENTS/METHODS: The study was performed as cross-sectional analysis in 104 RTR.
      CAC was determined as total calcium score (CS) and calcium mass (CM). Carotid
      femoral PWV was also measured. Sensitivity, specificity and receiver operating
      characteristic (ROC) curve were used to assess the performance of PWV as
      diagnostic test for presence of CAC. RESULTS: CAC was found in 69% of
      participants. PWV was higher in RTR with CAC than in RTR without CAC (10.2+/-2.2
      vs. 8.6+/-15; p<0.001). In univariate analysis CS was significantly correlated
      with age, duration of hypertension, waist circumference, PWV, hemoglobin
      concentration, and serum glucose. In multiple linear regression analysis CS was
      independently associated with age only, but not with PWV. Sensitivity and
      specificity of PWV>7.6m/s as cut-off for detecting CAC>0 was 0.889 and 0.406,
      respectively. Sensitivity and specificity of PWV>10.2m/s as cut-off for detecting
      severe CAC (CS>400) was 0.319 and 0.969, respectively. CONCLUSIONS: The study
      confirmed high prevalence of coronary artery calcification in renal transplant
      recipients. The study does not support the hypothesis that aortic stiffness is
      independently associated with coronary artery calcification in RTR. PWV
      measurement may be useful in excluding severe CAC in RTR.

PMID- 25951499
TI  - Two-Photon Absorbing Dyes with Minimal Autofluorescence in Tissue Imaging:
      Application to in Vivo Imaging of Amyloid-beta Plaques with a Negligible
      Background Signal.
AB  - Fluorescence imaging of tissues offer an essential means for studying biological
      systems. Autofluorescence becomes a serious issue in tissue imaging under
      excitation at UV-vis wavelengths where biological molecules compete with the
      fluorophore. To address this critical issue, a novel class of fluorophores that
      can be excited at ~900 nm under two-photon excitation conditions and emits in the
      red wavelength region (>=600 nm) has been disclosed. The new pi-extended dipolar
      dye system shows several advantageous features including minimal autofluorescence
      in tissue imaging and pronounced solvent-sensitive emission behavior, compared
      with a widely used two-photon absorbing dye, acedan. As an important application
      of the new dye system, one of the dyes was developed into a fluorescent probe for
      amyloid-beta plaques, a key biomarker of Alzheimer's disease. The probe enabled
      in vivo imaging of amyloid-beta plaques in a disease-model mouse, with negligible
      background signal. The new dye system has great potential for the development of
      other types of two-photon fluorescent probes and tags for imaging of tissues with
      minimal autofluorescence. 

PMID- 25951500
TI  - Experimental study of the coupling parameters influencing the terminal effects of
      thoracic blunt ballistic impacts.
AB  - The objective of the study is to better understand how blunt projectile ballistic
      parameters and material properties influence the events leading to injuries. The
      present work focuses on lateral thoracic impacts and follows an experimental
      approach. The projectiles are made with a soft foam nose assembled with a rigid
      rear plastic part. The dynamic properties of the foams were first determined
      using the Split Hopkinson Pressure Bar (SHPB) system. The impact forces on a
      rigid wall were then measured to provide reference load data. Lastly, shots were
      made on isolated thoraxes of porcine cadavers to investigate the response in the
      vicinity of the impact (wall displacements, rib accelerations and strains, rib
      fractures). Results show that the severity of the response appears to be mainly
      correlated with the impulse and with the pre-impact momentum. 

PMID- 25951501
TI  - Exploitation of very small particles to enhance the probative value of carpet
      fibers.
AB  - Environmentally acquired very small particles (VSP), present on the surfaces of
      carpet fibers, have shown potential for the association of fibers with their
      carpet source. To unlock this potential, research is required addressing a number
      of areas, including the application of methods under realistic casework
      conditions and the utilization of computational methods for the refinement and
      testing of the approach. In this work field collections of carpet fibers were
      conducted by crime scene practitioners under realistic casework conditions. VSP
      were isolated using previously developed methods, and analyses were conducted
      using SEM/EDS analytical protocols in an operational crime laboratory setting.
      Computational methods were designed, allowing sets of hundreds to thousands of
      VSP to be characterized. Classifiers were designed to associate and discriminate
      among specimens. These classifiers were applied to the VSP data for specimens
      collected by crime scene practitioners, as well as to a previously collected
      research dataset. Quantitative measures of correspondence and probative value
      were designed based on the classification measures and successfully applied to
      both sets of VSP data. Particle sets larger than 500 showed strong promise for
      quantitative associations with their sources. The use of larger numbers of target
      particle types (TPTs) showed strong promise to improve the performance of
      classification and association. Overall, the usefulness of VSP to provide
      objective, quantitative associations has been established. Because VSP are
      acquired post-manufacture, these methods can address fundamental limitations to
      probative value that arise when class characteristics, determined by manufacture,
      are shared among mass produced commodities. These findings are of broad
      significance for the future of trace evidence analysis. The results of this
      research are likely extendable, with minor modifications, to other trace evidence
      types (such as glass, tape and human hair), and are expected to contribute
      significantly for those types of trace evidence that have long been considered of
      low evidential value (such as undyed cotton and animal hairs). Furthermore,
      entirely new approaches to trace evidence are enabled by exploiting VSP profiles,
      such as comparing different types of trace evidence with one another and
      comparing VSP defined by crime scene or suspect environments to those on
      virtually any item of physical evidence. 

PMID- 25951502
TI  - Neural networks for identifying drunk persons using thermal infrared imagery.
AB  - Neural networks were tested on infrared images of faces for discriminating
      intoxicated persons. The images were acquired during controlled alcohol
      consumption by forty-one persons. Two different experimental approaches were
      thoroughly investigated. In the first one, each face was examined, location by
      location, using each time a different neural network, in order to find out those
      regions that can be used for discriminating a drunk from a sober person. It was
      found that it was mainly the face forehead that changed thermal behaviour with
      alcohol consumption. In the second procedure, a single neural structure was
      trained on the whole face. The discrimination performance of this neural
      structure was tested on the same face, as well as on unknown faces. The neural
      networks presented high discrimination performance even on unknown persons, when
      trained on the forehead of the sober and the drunk person, respectively. Small
      neural structures presented better generalisation performance. 

PMID- 25951503
TI  - Contextual and Cultural Influences on Parental Feeding Practices and Involvement
      in Child Care Centers among Hispanic Parents.
AB  - BACKGROUND: Parental feeding practices shape children's dietary preferences and
      behaviors, which can influence a child's weight status. Limited research exists
      on the precursors and contextual influences of feeding, particularly among
      Hispanic parents. Therefore, this study explored two areas potentially important
      for obesity prevention in young children: (1) precursors and contextual
      influences on parental feeding and (2) parental perceptions and knowledge of the
      child care food environment. METHODS: Four focus groups (n=36) were held with
      Hispanic parents, predominantly mothers, of preschool children at two child care
      centers. Parents were asked about influences on what and how they feed their
      children, awareness of the child care center feeding environment, and current
      involvement in the child care center. Themes were coded using NVivo10 software
      (QSR International, Melbourne, Australia). RESULTS: Participants' childhood
      experiences influenced how they feed their children. Parents stated that both
      husbands and grandparents often indulged their children with unhealthy foods and
      thought this interfered with their efforts to maintain a healthy home
      environment. Participants reported that what their children ate while in child
      care sometimes influenced the home feeding environment. CONCLUSIONS: Cultural and
      environmental factors influence parental feeding and involvement in the child
      care setting. Consistent with socioecological system theory, exploring
      interactions between the environment and culture using a family focus framework,
      such as the Family Ecological Model, could provide a better understanding of
      these influences among Hispanic parents. Future obesity prevention interventions
      with Hispanic families should be culturally relevant and target the different
      environments where children spend their time.

PMID- 25951505
TI  - Abstracts of the 49th Annual Scientific Meeting of the European Society for
      Clinical Investigation Cluj-Napoca, Romania 27 - 30 May 2015. Guest Editor:
      Professor Dan L. Dumitrascu, MD, PhD.

PMID- 25951504
TI  - Long-term outcome of prucalopride for chronic constipation: a single-centre
      study.
AB  - AIM: Newer 5-hydroxytryptamine agonists, such as prucalopride, have been
      demonstrated to be effective in the short term for treatment of chronic
      constipation. To date, few studies have investigated their medium- and long-term
      effectiveness. METHOD: An analysis was carried out of a prospectively maintained
      database of all patients started on prucalopride for chronic constipation between
      April 2011 and April 2014. Cleveland Clinic Constipation Score (CCCS)
      questionnaires were administered before starting treatment with prucalopride and
      at the first follow-up visit to assess change in CCCS scores in 50 randomly
      selected patients. RESULTS: A total of 155 patients (median age: 47 years; seven
      men) were started on prucalopride in this period. Of these, 16 (10%) had slow
      transit constipation, 31 (20%) had obstructive defaecation syndrome and 30 (19%)
      had a combination of both. Of these 155 patients, 78% patients were on three or
      more laxatives at the time of starting prucalopride. Patients were started on 1
      mg or 2 mg according to their age. The median follow-up period was 24 (range: 4
      40) months. At the first follow-up visit, 106 (68%) patients reported good
      symptomatic improvement, whereas the remainder had no response. Third of initial
      responders showed decreased efficacy after a median duration of 6 months and
      needed regular laxatives/irrigation. Of the 50 patients who filled in the CCCS
      questionnaires (15 patients were nonresponders), 32 (64%) reported improved
      scores with a median improvement of two points per criterion. CONCLUSION: This
      study provides evidence that prolonged use of prucalopride is effective in
      achieving a sustained benefit in the majority of patients.

PMID- 25951506
TI  - Population pharmacokinetic-pharmacodynamic modeling of omecamtiv mecarbil, a
      cardiac myosin activator, in healthy volunteers and patients with stable heart
      failure.
AB  - Data from 3 clinical trials of omecamtiv mecarbil in healthy volunteers and
      patients with stable heart failure (HF) were analyzed using a nonlinear mixed
      effects model to investigate omecamtiv mecarbil's pharmacokinetics and
      relationship between plasma concentration and systolic ejection time (SET) and
      Doppler-derived left ventricular outflow tract stroke volume (LVOTSV). Omecamtiv
      mecarbil pharmacokinetics were described by a linear 2-compartment model with a
      zero-order input rate for intravenous administration and first-order absorption
      for oral administration. Oral absorption half-life was 0.62 hours, and absolute
      bioavailability was estimated as 90%; elimination half-life was approximately
      18.5 hours. Variability in pharmacokinetic parameters was not explained by
      patient baseline characteristics. Omecamtiv mecarbil plasma concentration was
      directly correlated with increases in SET and LVOTSV between healthy volunteers
      and patients with HF. The maximum increase from baseline in SET (delta SET)
      estimated by an Emax model was 137 milliseconds. LVOTSV increased linearly from
      baseline by 1.6 mL per 100 ng/mL of omecamtiv mecarbil. Model-based simulations
      for several immediate-release oral dose regimens (37.5, 50, and 62.5 mg dosed
      every 8, 12, and 24 hours) showed that a pharmacodynamic effect (delta SET >=20
      milliseconds) could be maintained in the absence of excessive omecamtiv mecarbil
      plasma concentrations. 

PMID- 25951507
TI  - Role of RNase H1 in DNA repair: removal of single ribonucleotide misincorporated
      into DNA in collaboration with RNase H2.
AB  - Several RNases H1 cleave the RNA-DNA junction of Okazaki fragment-like RNA
      DNA/DNA substrate. This activity, termed 3'-junction ribonuclease (3'-JRNase)
      activity, is different from the 5'-JRNase activity of RNase H2 that cleaves the
      5'-side of the ribonucleotide of the RNA-DNA junction and is required to initiate
      the ribonucleotide excision repair pathway. To examine whether RNase H1 exhibits
      3'-JRNase activity for dsDNA containing a single ribonucleotide and can remove
      this ribonucleotide in collaboration with RNase H2, cleavage of a DNA8-RNA1
      DNA9/DNA18 substrate with E. coli RNase H1 and H2 was analyzed. This substrate
      was cleaved by E. coli RNase H1 at the (5')RNA-DNA(3') junction, regardless of
      whether it was cleaved by E. coli RNase H2 at the (5')DNA-RNA(3') junction in
      advance or not. Likewise, this substrate was cleaved by E. coli RNase H2 at the
      (5')DNA-RNA(3') junction, regardless of whether it was cleaved by E. coli RNase
      H1 at the (5')RNA-DNA(3') junction in advance or not. When this substrate was
      cleaved by a mixture of E. coli RNases H1 and H2, the ribonucleotide was removed
      from the substrate. We propose that RNase H1 is involved in the excision of
      single ribonucleotides misincorporated into DNA in collaboration with RNase H2. 

PMID- 25951508
TI  - The zebrafish, Danio rerio, as a model for Toxoplasma gondii: an initial
      description of infection in fish.

PMID- 25951509
TI  - Complex Reaction Environments and Competing Reaction Mechanisms in Zeolite
      Catalysis: Insights from Advanced Molecular Dynamics.
AB  - The methanol-to-olefin process is a showcase example of complex zeolite-catalyzed
      chemistry. At real operating conditions, many factors affect the reactivity, such
      as framework flexibility, adsorption of various guest molecules, and competitive
      reaction pathways. In this study, the strength of first principle molecular
      dynamics techniques to capture this complexity is shown by means of two case
      studies. Firstly, the adsorption behavior of methanol and water in H-SAPO-34 at
      350  degrees C is investigated. Hereby an important degree of framework
      flexibility and proton mobility was observed. Secondly, the methylation of
      benzene by methanol through a competitive direct and stepwise pathway in the AFI
      topology was studied. Both case studies clearly show that a first-principle
      molecular dynamics approach enables unprecedented insights into zeolite-catalyzed
      reactions at the nanometer scale to be obtained. 

PMID- 25951510
TI  - An early folding contact between Phe19 and Leu34 is critical for amyloid-beta
      oligomer toxicity.
AB  - Small hydrophobic oligomers of aggregation-prone proteins are thought to be
      generically toxic. Here we examine this view by perturbing an early folding
      contact between Phe19 and Leu34 formed during the aggregation of Alzheimer's
      amyloid-beta (Abeta40) peptide. We find that even conservative single mutations
      altering this interaction can abolish Abeta40 toxicity. Significantly, the
      mutants are not distinguishable either by the oligomers size or by the end-state
      fibrillar structure from the wild type Abeta40. We trace the change in their
      toxicity to a drastic lowering of membrane affinity. Therefore, nonlocal folding
      contacts play a key role in steering the oligomeric intermediates through
      specific conformations with very different properties and toxicity levels. Our
      results suggest that engineering the folding energy landscape may provide an
      alternative route to Alzheimer therapeutics. 

PMID- 25951511
TI  - Variation in Vowel Duration Among Southern African American English Speakers.
AB  - PURPOSE: Atypical duration of speech segments can signal a speech disorder. In
      this study, we examined variation in vowel duration in African American English
      (AAE) relative to White American English (WAE) speakers living in the same
      dialect region in the South to characterize the nature of systematic variation
      between the 2 groups. The goal was to establish whether segmental durations in
      minority populations differ from the well-established patterns in mainstream
      populations. METHOD: Participants were 32 AAE and 32 WAE speakers differing in
      age who, in their childhood, attended either segregated (older speakers) or
      integrated (younger speakers) public schools. Speech materials consisted of 14
      vowels produced in hVd-frame. RESULTS: AAE vowels were significantly longer than
      WAE vowels. Vowel duration did not differ as a function of age. The temporal
      tense-lax contrast was minimized for AAE relative to WAE. Vowels produced by
      females were significantly longer than vowels produced by males for both AAE and
      WAE. CONCLUSIONS: African American speakers should be expected to produce longer
      vowels relative to White speakers in a common geographic area. These longer
      durations are not deviant but represent a typical feature of AAE. This finding
      has clinical importance in guiding assessments of speech disorders in AAE
      speakers.

PMID- 25951512
TI  - The characterization, current medications, and promising therapeutics targets for
      premature ejaculation.
AB  - Premature ejaculation (PE) is the most prevalent male sexual dysfunction. This is
      associated with negative personal and interpersonal psychological outcomes. The
      pharmacologic treatment of PE includes the use of antidepressants, local
      anesthetic agents, and phosphodiesterase type 5 inhibitors. While numerous
      treatments can control PE, only antidepressants and topical anesthetic creams and
      sprays have recently been shown to be more effective. This review focuses on the
      physiology and pharmacology of ejaculation, the pathophysiology of PE and the
      most effective pharmacological treatment of PE. Pharmacotherapy of PE with off
      label short-acting selective serotonin reuptake inhibitors (SSRIs) is common,
      effective, and safe. Dapoxetine, a SSRI with a short half-life, has been recently
      evaluated for the treatment of PE by several countries and results are promising.
      In clinical practice, follow-up side effects are an important part of the
      management strategy for PE. The understanding of etiology, pathophysiology, and
      treatment modalities of PE would be beneficial to clinician in helping patients
      with this disappointing sexual problem. 

PMID- 25951513
TI  - Demethylation of arsenic limits its volatilization in fungi.
AB  - Arsenic (As) biomethylation is increasingly being regarded as a promising method
      to volatize As from the environment; however, the As volatilization efficiency of
      most microorganisms is low. Here, the speciation transformation of
      dimethylarsinic acid (DMA) as an important methylation intermediate in the cells
      of Fusarium oxysporum CZ-8F1, Penicillium janthinellum SM-12F4, and Trichoderma
      asperellum SM-12F1 were investigated. These fungal strains have been certified to
      volatilize As from As-loaded environment. In situ X-ray absorption near edge
      structure (XANES) indicated that demethylation of DMA with methylarsonic acid
      (MMA), arsenate [As(V)], and arsenite [As(III)] as intermediates or products
      occurred in fungal cells after exposure to DMA for 15 days. 36.7-55.7% of the
      original DMA could lose one or two methyl groups and be changed into MMA or
      inorganic As. Chromatographic separation of the cell lysates also supported these
      findings. Thus it comes that demethylation might be a remarkable internal factor
      limiting As volatilization efficiency. 

PMID- 25951514
TI  - The biological function of an insect antifreeze protein simulated by molecular
      dynamics.
AB  - Antifreeze proteins (AFPs) protect certain cold-adapted organisms from freezing
      to death by selectively adsorbing to internal ice crystals and inhibiting ice
      propagation. The molecular details of AFP adsorption-inhibition is uncertain but
      is proposed to involve the Gibbs-Thomson effect. Here we show by using unbiased
      molecular dynamics simulations a protein structure-function mechanism for the
      spruce budworm Choristoneura fumiferana AFP, including stereo-specific binding
      and consequential melting and freezing inhibition. The protein binds indirectly
      to the prism ice face through a linear array of ordered water molecules that are
      structurally distinct from the ice. Mutation of the ice binding surface disrupts
      water-ordering and abolishes activity. The adsorption is virtually irreversible,
      and we confirm the ice growth inhibition is consistent with the Gibbs-Thomson
      law. 

PMID- 25951515
TI  - SMC condensin entraps chromosomal DNA by an ATP hydrolysis dependent loading
      mechanism in Bacillus subtilis.
AB  - Smc-ScpAB forms elongated, annular structures that promote chromosome
      segregation, presumably by compacting and resolving sister DNA molecules. The
      mechanistic basis for its action, however, is only poorly understood. Here, we
      have established a physical assay to determine whether the binding of condensin
      to native chromosomes in Bacillus subtilis involves entrapment of DNA by the Smc
      ScpAB ring. To do so, we have chemically cross-linked the three ring interfaces
      in Smc-ScpAB and thereafter isolated intact chromosomes under protein denaturing
      conditions. Exclusively species of Smc-ScpA, which were previously cross-linked
      into covalent rings, remained associated with chromosomal DNA. DNA entrapment is
      abolished by mutations that interfere with the Smc ATPase cycle and strongly
      reduced when the recruitment factor ParB is deleted, implying that most Smc-ScpAB
      is loaded onto the chromosome at parS sites near the replication origin. We
      furthermore report a physical interaction between native Smc-ScpAB and
      chromosomal DNA fragments. 

PMID- 25951516
TI  - Receptor tyrosine kinases modulate distinct transcriptional programs by
      differential usage of intracellular pathways.
AB  - Receptor tyrosine kinases (RTKs) signal through shared intracellular pathways yet
      mediate distinct outcomes across many cell types. To investigate the mechanisms
      underlying RTK specificity in craniofacial development, we performed RNA-seq to
      delineate the transcriptional response to platelet-derived growth factor (PDGF)
      and fibroblast growth factor (FGF) signaling in mouse embryonic palatal
      mesenchyme cells. While the early gene expression profile induced by both growth
      factors is qualitatively similar, the late response is divergent. Comparing the
      effect of MEK (Mitogen/Extracellular signal-regulated kinase) and PI3K
      (phosphoinositide-3-kinase) inhibition, we find the FGF response is MEK
      dependent, while the PDGF response is PI3K dependent. Furthermore, FGF promotes
      proliferation but PDGF favors differentiation. Finally, we demonstrate
      overlapping domains of PDGF-PI3K signaling and osteoblast differentiation in the
      palate and increased osteogenesis in FGF mutants, indicating this differentiation
      circuit is conserved in vivo. Our results identify distinct responses to PDGF and
      FGF and provide insight into the mechanisms encoding RTK specificity. 

PMID- 25951517
TI  - RIPOSTE: a framework for improving the design and analysis of laboratory-based
      research.
AB  - Lack of reproducibility is an ongoing problem in some areas of the biomedical
      sciences. Poor experimental design and a failure to engage with experienced
      statisticians at key stages in the design and analysis of experiments are two
      factors that contribute to this problem. The RIPOSTE (Reducing IrreProducibility
      in labOratory STudiEs) framework has been developed to support early and regular
      discussions between scientists and statisticians in order to improve the design,
      conduct and analysis of laboratory studies and, therefore, to reduce
      irreproducibility. This framework is intended for use during the early stages of
      a research project, when specific questions or hypotheses are proposed. The
      essential points within the framework are explained and illustrated using three
      examples (a medical equipment test, a macrophage study and a gene expression
      study). Sound study design minimises the possibility of bias being introduced
      into experiments and leads to higher quality research with more reproducible
      results. 

PMID- 25951519
TI  - Molecular identification and functional characterization of the first Nalpha
      acetyltransferase in plastids by global acetylome profiling.
AB  - Protein N(alpha) -terminal acetylation represents one of the most abundant
      protein modifications of higher eukaryotes. In humans, six N(alpha) 
      acetyltransferases (Nats) are responsible for the acetylation of approximately
      80% of the cytosolic proteins. N-terminal protein acetylation has not been
      evidenced in organelles of metazoans, but in higher plants is a widespread
      modification not only in the cytosol but also in the chloroplast. In this study,
      we identify and characterize the first organellar-localized Nat in eukaryotes. A
      primary sequence-based search in Arabidopsis thaliana revealed seven putatively
      plastid-localized Nats of which AT2G39000 (AtNAA70) showed the highest
      conservation of the acetyl-CoA binding pocket. The chloroplastic localization of
      AtNAA70 was demonstrated by transient expression of AtNAA70:YFP in Arabidopsis
      mesophyll protoplasts. Homology modeling uncovered a significant conservation of
      tertiary structural elements between human HsNAA50 and AtNAA70. The in vivo
      acetylation activity of AtNAA70 was demonstrated on a number of distinct protein
      N(alpha) -termini with a newly established global acetylome profiling test after
      expression of AtNAA70 in E. coli. AtNAA70 predominately acetylated proteins
      starting with M, A, S and T, providing an explanation for most protein N-termini
      acetylation events found in chloroplasts. Like HsNAA50, AtNAA70 displays
      N(epsilon) -acetyltransferase activity on three internal lysine residues. All MS
      data have been deposited in the ProteomeXchange with identifier PXD001947
      (http://proteomecentral.proteomexchange.org/dataset/PXD001947).

PMID- 25951520
TI  - Fluorinated Alcohols as Activators for the Solvent-Free Chemical Fixation of
      Carbon Dioxide into Epoxides.
AB  - The addition of fluorinated alcohols to onium salts provides highly efficient
      organocatalysts for the chemical fixation of CO2 into epoxides under mild
      experimental conditions. The combination of online kinetic studies, NMR
      titrations and DFT calculations allows understanding this synergistic effect that
      provides an active organocatalyst for CO2 /epoxides coupling. 

PMID- 25951518
TI  - Coordination of peptidoglycan synthesis and outer membrane constriction during
      Escherichia coli cell division.
AB  - To maintain cellular structure and integrity during division, Gram-negative
      bacteria must carefully coordinate constriction of a tripartite cell envelope of
      inner membrane, peptidoglycan (PG), and outer membrane (OM). It has remained
      enigmatic how this is accomplished. Here, we show that envelope machines
      facilitating septal PG synthesis (PBP1B-LpoB complex) and OM constriction (Tol
      system) are physically and functionally coordinated via YbgF, renamed CpoB
      (Coordinator of PG synthesis and OM constriction, associated with PBP1B). CpoB
      localizes to the septum concurrent with PBP1B-LpoB and Tol at the onset of
      constriction, interacts with both complexes, and regulates PBP1B activity in
      response to Tol energy state. This coordination links PG synthesis with OM
      invagination and imparts a unique mode of bifunctional PG synthase regulation by
      selectively modulating PBP1B cross-linking activity. Coordination of the PBP1B
      and Tol machines by CpoB contributes to effective PBP1B function in vivo and
      maintenance of cell envelope integrity during division. 

PMID- 25951522
TI  - Immunotherapy: combine and conquer.

PMID- 25951521
TI  - Dual-color dual-focus line-scanning FCS for quantitative analysis of receptor
      ligand interactions in living specimens.
AB  - Cellular communication in multi-cellular organisms is mediated to a large extent
      by a multitude of cell-surface receptors that bind specific ligands. An in-depth
      understanding of cell signaling networks requires quantitative information on
      ligand-receptor interactions within living systems. In principle, fluorescence
      correlation spectroscopy (FCS) based methods can provide such data, but live-cell
      applications have proven extremely challenging. Here, we have developed an
      integrated dual-color dual-focus line-scanning fluorescence correlation
      spectroscopy (2c2f lsFCS) technique that greatly facilitates live-cell and tissue
      experiments. Absolute ligand and receptor concentrations and their diffusion
      coefficients within the cell membrane can be quantified without the need to
      perform additional calibration experiments. We also determine the concentration
      of ligands diffusing in the medium outside the cell within the same experiment by
      using a raster image correlation spectroscopy (RICS) based analysis. We have
      applied this robust technique to study the interactions of two Wnt antagonists,
      Dickkopf1 and Dickkopf2 (Dkk1/2), to their cognate receptor, low-density
      lipoprotein-receptor related protein 6 (LRP6), in the plasma membrane of living
      HEK293T cells. We obtained significantly lower affinities than previously
      reported using in vitro studies, underscoring the need to measure such data on
      living cells or tissues. 

PMID- 25951523
TI  - Buzzkill: Regulatory uncertainty plagues rollout of genetically modified
      mosquitoes.

PMID- 25951525
TI  - Corrections.

PMID- 25951526
TI  - A B cell-dependent mechanism restrains T cell transendothelial migration.

PMID- 25951527
TI  - A cross-talk network that facilitates tumor virotherapy.

PMID- 25951528
TI  - Duodenal energy sensing regulates hepatic glucose output.

PMID- 25951529
TI  - Repurposing a leukocyte elastase inhibitor for neuropathic pain.

PMID- 25951531
TI  - Corrigendum: Translation from a DMD exon 5 IRES results in a functional
      dystrophin isoform that attenuates dystrophinopathy in humans and mice.

PMID- 25951532
TI  - Corrigendum: Remote regulation of glucose homeostasis in mice using genetically
      encoded nanoparticles.

PMID- 25951530
TI  - Translational value of mouse models in oncology drug development.
AB  - Much has been written about the advantages and disadvantages of various oncology
      model systems, with the overall finding that these models lack the predictive
      power required to translate preclinical efficacy into clinical activity. Despite
      assertions that some preclinical model systems are superior to others, no single
      model can suffice to inform preclinical target validation and molecule selection.
      This perspective provides a balanced albeit critical view of these claims of
      superiority and outlines a framework for the proper use of existing preclinical
      models for drug testing and discovery. We also highlight gaps in oncology mouse
      models and discuss general and pervasive model-independent shortcomings in
      preclinical oncology work, and we propose ways to address these issues. 

PMID- 25951534
TI  - Corrigendum: PAI-1 mediates the antiangiogenic and profibrinolytic effects of 16K
      prolactin.

PMID- 25951535
TI  - Stable pi Radical from a Contracted Doubly N-Confused Hexaphyrin by Double
      Palladium Metalation.
AB  - A contracted doubly N-confused dioxohexaphyrin derivative served as a
      dinucleating metal ligand for unsymmetrical coordination. The complexation of two
      palladium(II) cations led to the formation of pi-radical species that were
      persistent in atmospheric air in the presence of moisture. Effective
      delocalization of an unpaired electron over the hexaphyrin backbone could
      contribute to the distinct chemical stability. 

PMID- 25951536
TI  - Clinical performance of two-piece zirconia implants in the posterior mandible and
      maxilla: a prospective cohort study over 2 years.
AB  - OBJECTIVES: To assess the clinical performance of two-piece zirconium implants
      over a period of up to 2 years. MATERIAL & METHODS: A total of 52 patients with
      single-tooth gaps in the posterior mandible or maxilla received the same type of
      a two-piece zirconium implant system with customized heights of the transmucosal
      aspect. Fibreglass abutments were cemented and restored with fixed all-ceramic
      single crowns using a conventional loading protocol. The cumulative survival rate
      (primary outcome) was calculated according to the life table method, and Kaplan
      Meier survival curves were used to estimate the survival function. Covariates
      (gender, implant position, implant diameter/length, oral surgeon) were tested
      using log-rank tests. RESULTS: A total of two target implants in 2 patients were
      lost after a functioning time of 8 months. The cumulative survival rate was
      95.8%, and the mean survival time amounted to 32.9 months. Log-rank tests
      revealed a significant association for the covariate "oral surgeon" (P = 0.047).
      The Kaplan-Meier estimates of mechanical/technical and biological complications
      amounted to 2.1% and 37.5%, respectively. All implant sites revealed a marked
      increase of the vestibular mucosal level and gain of keratinized tissue at 24
      months. CONCLUSION: Within the limitations of a prospective cohort study, it was
      concluded that this two-piece zirconium implant/fibreglass abutment system can be
      successfully used in the clinical indication investigated.

PMID- 25951538
TI  - 25 years of laparoscopic surgery, personal reflections: problems in laparoscopy
      in the past and present.
AB  - Laparoscopy was developed by Kalk of Germany in 1929 as a routine procedure in
      internal medicine for diagnosis of liver diseases. Air was insufflated to create
      the pneumoperitoneum, and an electric lamp was placed at the end of the
      laparoscope to provide illumination of the abdominal cavity. Entrance into the
      peritoneal cavity was in the upper abdomen two finger breadths under the ribs.
      The danger of damaging the bowel by burning, etc. was very low. Previously
      laparotomized patients were considered an absolute contraindication for
      Laparoscopy. In 1946 Palmer, France turned the laparoscope from the upper abdomen
      to look into the lower abdomen. He called this technique Coelioscopy. It was used
      as for a diagnostic procedure mainly for the sterility patient in Gynecology. For
      coelioscopy Palmer used the same instruments as were used for Laparoscopy. The
      danger of burning bowel increased enormously as the protector of the upper
      abdomen, the omentum, was missing in the lower abdomen. 

PMID- 25951537
TI  - Fine-scale belowground species associations in temperate grassland.
AB  - Evaluating how belowground processes contribute to plant community dynamics is
      hampered by limited information on the spatial structure of root communities at
      the scale that plants interact belowground. In this study, roots were mapped to
      the nearest one mm and molecularly identified by species on vertical (0-15 cm
      deep) surfaces of soil blocks excavated from dry and mesic grasslands in
      Yellowstone National Park (YNP) to examine the spatial relationships among
      species at the scale that roots interact. Our results indicated that average
      interspecific root - root distances for the majority of species were within a
      distance (3 mm) that roots have been shown to compete for resources. Most species
      placed their roots at random, although low root numbers for many species probably
      led to overestimating the occurrence of random patterns. According to theory, we
      expected that most of the remaining species would segregate their root systems to
      avoid competition. Instead we found that more species aggregated than segregated
      from others. Based on previous investigations, we hypothesize that species
      aggregate to increase uptake of water, nitrogen and/or phosphorus made available
      by neighbouring roots, or as a consequence of a reduction in the pathogenicity of
      soil biota growing in multispecies mixtures. Our results indicate that YNP
      grassland root communities are organized as closely interdigitating networks of
      species that potentially can support strong interactions among many species
      combinations. Future root research should address the prevalence and functional
      consequences of species aggregation across plant communities. 

PMID- 25951539
TI  - Horizons in endoscopic surgery.
AB  - Dramatic advances continue to occur with video-directed endoscopic operations.
      This commentary will follow the same format as the one in the previous edition
      two years ago. Most of the predictions anticipated in our last writing have been
      met or exceeded. Change will continue to accelerate, though the individual
      innovations will be of smaller magnitude. 

PMID- 25951540
TI  - Avoiding laparoscopic complications.
AB  - Two years after laparoscopic cholecystectomy was introduced, and new horizons in
      laparoscopic surgery were being developed, a noted academic surgeon told me that
      although he had initially doubted the viability of laparoscopic 'cholecystectomy,
      he had become an avid supporter. He cautioned, however, that many surgeons would
      perform the operation with minimal training and marginal laparoscopic skills and
      that the injury rate would be devastating. Unfortunately, that prophecy has come
      to pass. In this dissertation, I would like to discuss some of those
      complications and how to avoid them. I choose not to dwell on minor or peripheral
      complications such as wound infection, pneumonia, deep venous thrombosis, urinary
      tract infection and the like, but rather, concentrate on complications related
      directly to laparoscopy and Iaparoscopic surgery. Laparoscopic complications are
      either a direct result of poor laparoscopic technique or related to anatomic
      misidentification. Technical complications include major vascular or intestinal
      injury or insufflation injury. Anatomic injuries usually involve the bile ducts,
      ureter or sensory nerves due to poor dissection and identification. 

PMID- 25951541
TI  - Laparoscopic common bile duct exploration.
AB  - As is pointed out in multiple publications, laparoscopic cholecystectomy has
      rapidly gained recognition an acceptance in the management of chronic
      cholecystitis and most cases of acute cholecystitis.A low incidence of
      complications accompanies laparoscopic cholecystectomy now that experience has
      been gained with this procedure by laparoscopically skilled surgeons.v-" However,
      the management of stones found or suspected in the common bile duct continues to
      be controversial. The gold standard for treatment of choledocholisthiasis remains
      the open exploration of the bile ducts with a reported mortality of 0.3%-0.19%
      and a rate of retained stones of between 2-4 %. Both surgeons and
      gastroenterologists skilled in endoscopy have espoused endoscopic retrograde
      cholangiopanreatography and sphincterotomy (ERCP/ES) preoperatively or
      postoperatively for the treatment of known common bile duct stones This approach
      adds additional procedures and potentially compounds the complications of the
      separate operative interventions to deal with the diseased gallbladder and to
      clear the common bile duct of obstruction. In several series of patients the
      morbidity of endoscopic sphincterotomy has ranged from 9-16%, with bleeding,
      acute pancreatitis, acute cholangitis, residual stones, duodenal perforation, and
      common bile duct perforation the leading causes of complications. There continues
      to be an incidence of retained stones of 9.1-14.7% with ERCP/ES.Furthermore, as
      high as 86% of indiscriminate preoperative ERCP studies show no evidence of
      stones in the common bile duct, making this an unnecessary intervention in such
      cases. There has been no consistent reduction in subsequent mortality in
      complicated biliary cases by the use of ERCP/ES alone, even with the gallbladder
      left in situ. 

PMID- 25951542
TI  - Laparoscopic herniorrhaphy.
AB  - With the introduction of laparoscopic cholecystectomy, the general surgery
      community was introduced to the world of minimally invasive surgery. In less than
      two years, just about every meeting, journal, and medical trade show demonstrated
      this "new" found technique. Surgeons have been very quick to pick up on the
      laparoscopic technique, and have actively sought other applications for the
      laparoscopic approach. With approximately 400,000 inguinal hernia repairs being
      performed in the United States annually, I the laparoscopic repair of this common
      malady was very quickly embraced as a possible new application. The concept of a
      trans-abdominal repair of a hernia defect is not new, having been described as
      early as the original description of "the modem day" hernia repair by Marcey. A
      trans-abdominallaparoscopic repair has a potential advantage over a conventional
      groin approach by it's avoidance of the groin incision and the need to mobilize
      the cord structures. This not 'only minimizes post operative pain, but also the
      risk of long term morbidity.related to mobilization of the cord. (neuroma
      formation secondary to injury of the cutaneous nerves, epididymitis and orchitis)
      There is also the possible advantage of an earlier return to normal activities.
      In contrast to laparoscopic cholecystectomy, there are technical differences
      between the laparoscopic and open hernia repairs. This difference raises the
      question as to whether or not the laparoscopic repair will yield results that
      will compare with an open technique. Open surgical techniques are considered a
      safe and effective means of treating inguinal hernias. The operation avoids the
      violation of the abdominal cavity, can be performed under local anesthesia, and
      is often performed on an outpatient basis. This raises the question "why via the
      laparoscope"? Despite reports from specialized hernia centers reporting a
      recurrence rate of 0 to 2 percent, large series from community based surgeons
      continue to report recurrence rates in the range of 5 to 10 percent. This
      recurrence rate has changed very little since Bassini reported a recurrence rate
      of 10 percent at the turn of the century. Although the overall morbidity of an
      open repair is only in the range of 2 percent, this morbidity .consists almost
      entirely of complications related to the wound and mobilization of the cord
      structures. The standard open hernia repair is not a perfect operation, and any
      attempt at its improvement is warranted. Since the laparoscopic repairs
      approaches the defect from within avoiding a large surgical incision and
      mobilization of the cord structures, the repair logically makes sense. Despite
      the intuitive advantages of the laparoscopic repair, questions regarding
      recurrence rates and safety of the laparoscopic repair still need to be answered.

PMID- 25951543
TI  - Colon resection.
AB  - Laparoscopic surgery has been in existence for nearly a century, yet its
      widespread acceptance and application in the field of general surgery is a
      relatively recent occurrence. With the rapid acceptance of laparoscopic
      cholecystectomy, surgeons have sought other procedures which would be amenable to
      laparoscopic approaches. This, combined with a technology boom in laparoscopic
      instrumentation has made possible the development of advanced laparoscopic
      procedures such as colectomy. It is important to emphasize that laparoscopic
      colon surgery is still in an evolutionary stage, and that the procedures
      described are being continually refined as more experience is gained, as newer
      instruments are developed, and as software and video applications continue to
      improve. Nevertheless, the goal of any surgeon performing a laparoscopic
      procedure should be to perform an operation identical to the one done through a
      large incision. 

PMID- 25951544
TI  - Laparoscopic fundoplication.
AB  - Gastroesophageal reflux disease (GERD) is a common disorder of the foregut. Over
      the past twenty-five years the developement of instrumentation and techniques to
      study GERD have revealed it to be a complex disorder. Increasingly effective
      pharmacotherapeutics have been developed over the same time frame. As such the
      great majority of patients are adequately treated by a medical regimen. Patients
      who are medically refractory or those requiring long term medications are
      potential candidates for anti-reflux surgery. Over the past decade decreasing
      numbers of anti-reflux surgical procedures have been performed. The two main
      reasons are improved pharmacology i.e. Prilosec and the complication rate
      associated with antireflux surgery. The laparoscopic performance of anti-reflux
      surgery offers dramatic benefits to the patient. As in the performance of
      laparoscopic cholecystectomies the decreased postoperative morbidity and rapid
      return to normal activities ensures overall cost savings. We present our
      experience with laparoscopic anti-reflux surgery to include the work up,
      technique, results, and a new laparoscopic anti-reflux procedure. 

PMID- 25951545
TI  - Thoracoscopic sympathicotomy.
AB  - Thoracoscopy - Looking into the thoracic cavity was first described in 1910 by
      the Swedish physician, Jacobeus. He used a cystoscope intrapleuraly in order to
      diagnose pleural diseases. He also used his method for cutting adhesions in order
      to achieve collapse of the lung in patients with tuberculosis of the lung.
      Thoracic sympathicotomy was first performed by Kotzareff in 1920. The operation
      was found to be effective for treatment of palmar hyperhidrosis. Different open
      techniques for sympathicotomy have since been described, the most common being
      the dorsal approach by Cloward in 1969. Sympathicotomy was found to be effective
      not only for palmar, but also axillar hyperhidrosis, vascular insufficiency of
      the arm and hand, causalgia and angina pectoris (Lindgren 1950). However, the
      operation using the open technique was difficult and, though effective, not many
      patients were prepared to meet the demands for problems such as hyperhidrosis.
      Therefore, the operation became rather common. In the middle of the 1940's,
      several attempts were made to make the sympathicotomy through thoracoscopic
      approach and in 1951, Kux described a large number of patients treated in this
      way for many different diseases such as duodenal ulcer, diabetes mellitus, as
      well as the generally accepted indications. He published his experiences in a
      book; but for some obscure reason, his technique did not achieve general
      acceptance. In the late 1970's and the 1980's, the principle was again taken up
      by different centers (Byrnes, et. al.). I will describe here a technique which
      can be regarded as a simplification of previous methods. The technique was
      elaborated in our department and the first operation was performed in 1987
      (Claes, et. al.). By June 1993, six hundred and seventy operations have been
      carried out. 

PMID- 25951546
TI  - Upper thoracic sympathectomy.
AB  - In the extremities, the vascular response to sympathetic stimulation is
      vasoconstriction with blanching and cooling of skin and increased sweating,
      whereas, blocking of the sympathetic system results in increased blood flow
      through cutaneous arteriovenous fistulae and cessation of sweating, thereby,
      resulting in increased dryness, warmth and accentuation of pink color. In the
      past, sympathetic denervation of the upper extremity was suggested as a treatment
      of many disorders; bronchial asthma, essential hypertension, peptic ulcer
      disease, hyperthyroidism, hyperhidrosis, vasospastic syndromes (Raynaud's
      disease), thoracic outlet syndrome, causalgia, post-traumatic sympathetic
      dystrophy (Sudeckatrophy), and angina pectoris. The indications for upper
      thoracic sympathectomy are limited today to hyperhidrosis, causalgia, severe
      vasospastic disorders, and ischemic changes of the extremities (Buerger's
      disease). 

PMID- 25951547
TI  - Thoracoscopic treatment of recurrent pneumothorax by pleurabrushing and argon
      beam coagulation.
AB  - There is no consensus in treating relapsing pneumothorax and pleural effusion.
      Various types of treatment exist. While open chest surgery with mechanical
      pleurodesis or pleurectomy is effective, with a recurrence rate close to zero,
      for patients in poor conditions this treatment may be disadvantageous because of
      its invasiveness. Therefore minimally invasive techniques using antibiotics,
      fibrin glue, talcum, kaolin, blood and silver nitrate have been described.
      Several side effects accompany these agents, and the recurrence rate is between 5
      39%. New video-assisted thoracoscopic techniques have enabled surgeons to combine
      the effectiveness of pleurectomy with minimal invasiveness. Results using these
      techniques are encouraging. As with open pleurectomy, bleeding complications have
      been reported, Further disadvantages have to be considered, such as the effect of
      destroying the parietal layer of the pleura, which may complicate subsequent
      operations in the thoracic cavity. A technique for avoiding this pleural injury,
      while maintaining the same efficiency as open pleural abrasion and coagulation is
      described below. 

PMID- 25951548
TI  - Thoracoscopic surgery spontaneous pneumothorax and nodules of the lung.
AB  - Indications and principles of the surgical procedure should be the same for
      endoscopic and open surgery. Those performing endoscopic surgery should be
      familiar with the corresponding open procedure, thus being capable to manage
      complications. Unbiased decision for endoscopic or open procedure might be
      compromised by lack of experience in one of them. Keeping this in mind, the
      trauma of surgical access for treatment of some diseases may be diminished by the
      thoracoscopic approach. There are only few established or almost established
      indications for thoracoscopic surgery. Since January 1990, we have gained some
      experience with spontaneous pneumothorax and nodules of the lung. Our patients
      have been followed-up carefully and the future results will have to be compared
      with those obtained by conventional surgery (thoracotomy). Our surgical technique
      and early results will be described in the following. 

PMID- 25951549
TI  - Laparoscopy in the trauma patient.
AB  - The first laparoscopic exam of the abdominal viscera was done by Keillng in 1902.
      Since that time, laparoscopy has been used more extensively in abdominal and
      pelvic disorders by gynecologists and gastroenterologists than general surgeons.
      However, since the introduction of laparoscopic cholecystectomy in the 1980s by
      Mouret in France and Muhe in Germany, laparoscopy has been embraced by the
      general surgeon and has exponentially increased in number and types of procedures
      being done. New technology, such as the enhancement of video image along with
      better instrumentation, has further accelerated the acceptance of "minimally
      invasive" surgery in all surgical specialties. 

PMID- 25951550
TI  - Endoscopic innovations.
AB  - The goal of this chapter is to describe the evolution and implementation of
      several new interventional technologies which expand the capabilities for less
      invasive surgery. These technologies, including laparoscopic transcystic duct
      common bile duct exploration, fallopian tube endoscopy, and laser lithotripsy,
      are all based on the use of new fiberoptics and laser technology. While the
      application of these technologies may appear unrelated, each specialty has
      borrowed technology and techniques from other disciplines to develop less
      invasive forms of therapy. Until recently, transfer of new techniques between
      different medical specialities has been impeded by a lack of communication. This
      lack of communication has been a primary impediment to the transfer of enabling
      technologies from one discipline to another. The Laser Research and Technology
      Development Program at Cedars-Sinai Medical Center provides the physical setting
      and administrative support for collaborative research which emphasizes technology
      transfer. Focused, well defined research projects are developed to solve a
      particular problem. New technologies which might provide potential solutions to
      the problem are systematically examined for feasibility, cost, ease of
      implementation and application to medicine. Successful application of new
      technologies to medicine requires a well defined, goal-oriented program with the
      support of a broadly-based research team including physicists, chemists,
      engineers, biologists, and physicians. 

PMID- 25951551
TI  - Laparoscopic ultrasonography.
AB  - Laparoscopic surgery imposes limitations on the surgeon not present in open
      surgery, including restricted degrees of freedom of instrument movement, lack of
      binocular vision, and severely restricted tactile feedback from the tissues. An
      aggressive effort is being made to apply technology to overcome some of these
      limitations and the adaptation of ultrasound probes for laparoscopic use now
      allows the surgeon to not only examine the surface of structures but to look into
      them with ultrasonic imaging. Laparoscopic ultrasonography has been used to
      evaluate the biliary tree during laparoscopic cholecystectomy both to delineate
      the biliary anatomy and look for common duct stones. This technology may have its
      widest use in the future in examining the liver for metastatic disease in
      patients undergoing laparoscopic colon resection. It must be realized that this
      is a technology in its infancy and further studies need to be done to evaluate
      areas where laparoscopic ultrasonography will have its greatest clinical utility.

PMID- 25951552
TI  - Gasless laparoscopic surgery.
AB  - Conventional laparoscopic surgery requires pneumoperitoneum to elevate the
      abdominal wall for maintaining expansion in an operating field. A continuous
      insufflation of a noncombustible, soluble gas in a sealed environment is
      essential. At 15 mm Hg intra-abdominal pressure (the upper limit of intra
      abdominal pressure used by most surgeons), significant cardiovascular changes
      have been observed. These changes are caused by diaphragm elevation and inferior
      vena cava compression. Elevation of the diaphragm also causes a decrease in tidal
      volume with resulting pulmonary dysfunction. In conventional practice where C02
      is used to create pneumoperitoneum, increased absorption of the gas causes
      metabolic acidosis and increased intracerebral pressure. Therefore, in patients
      with intracranial pathology, the use of C02 pneumoperitoneum is not desirable.
      Compression of the vena cava by pneumoperitoneum results in venous stasis in the
      lower extremities. Deep venous thrombosis has not been a major problem for
      gynecologists because pelvic peritoneoscopy is performed in the Trendelenburg
      position where blood return is enhanced. More lower extremity thromboembolism
      would be expected when more upper abdominal laparoscopic procedures are performed
      with the patient positioned in a reversed Trendelenburg position. 

PMID- 25951553
TI  - Endoscopic suturing and knotting.
AB  - As the minimally invasive approach to surgery has taken a firm foothold the new
      quest has been to find if there were any limits to procedures being done entirely
      "closed". The obvious patient and cost benefits had already been established,
      thus many a creative and adventurous surgeon busily explored these possibilities.
      It has already been demonstrated clinically that laparoscopic tubotubal
      reanastomosis is feasible and in the experimental setting laparoscopic vesico
      urethral anastomosis (following laparoscopic radical prostatectomy), and
      fetoscopic repair of a cleft lip, all using fine sutures, are possible. The
      answer seemed to lie in the limitations: setup, skill, technique, visualization,
      and instrumentation. Problems with visualization have been addressed during the
      past decade and substantial gains have been made in optical and audio-visual
      technology. Instrumentation lagged behind, not only because of astronomical
      demand but also because of the lack of understanding of the exact needs of the
      laparoscopic surgeon. A good deal of borrowing or adaptation of conventional
      instruments has occurred which has been beneficial in the sense that these were
      familiar to surgeon (habit is stronger than logic). The problem was the that
      highly restricted operative field rendered many of them nearly useless. New
      instruments had to be developed and many innovative designs have since become
      available for almost everything but suturing and knot tying. 

PMID- 25951554
TI  - Laparoscopic electrosurgery: complications and prevention.
AB  - Even though monopolar electrosurgery has been utilized laparoscopically for over
      two decades, post procedural complications, including bowel burns, remain
      significant. Initially employed by gynecologists, electrosurgical cutting and
      coagulation is rapidly becoming popular with general surgeons and urologists.
      Electrosurgery in a closed environment presents a special set of problems and in
      order to prevent complications surgeons need to familiarize themselves with the
      basic science of electrosurgery and the potential laparoscopic complications.
      This chapter presents an overview of the physics of electrosurgery with special
      attention to laparoscopic use. Also discussed are two technologies, a shielding
      monitoring system for monopolar electrodes and bipolar electrodes, which minimize
      and/or eliminate potential laparoscopic complications associated with the use of
      electrosurgery. 

PMID- 25951555
TI  - Liver xenotransplantation.
AB  - During the past 30 years orthotopic liver transplantation has become a highly
      successful form of surgical treatments. The significant advances achieved in this
      field have led to an increased demand for organs and created a wide gap between
      organ availability and organ supply. A wider availability of organs for
      transplantation would allow an expansions rather than a contraction of the
      indications for transplantation, and, at the same time a relaxation of the
      patient selection criteria. All these facts clearly justify the renewed interest
      observed in the last decade in xenotransplantation. The original concept of
      xenografting, meaning the transplantation of cells, tissues, or organs between
      different species, is so ancient that it is easily recognizable in Greek and
      Roman mythology. The centaur Chiron, the teacher of Esculapius, and the Chimera
      are legendary examples of discordant xenogeneic creatures. However, it is only
      during this century that scientists have been able to bring this idea into the
      clinical arena. The early efforts were prompted by the shortage of humans organs
      at a time when there were few alternatives for treating end-stage organ failure. 

PMID- 25951556
TI  - Transplantation immunology.
AB  - The replacement of diseased or damaged organs by transplantation became a reality
      in 1954, when a kidney was transplanted from one monozygotic twin to another.
      Barring technical difficulties, a graft between genetically identical (syngeneic)
      individuals is readily accepted and is termed an isograft. An allograft is a
      transplant between allogeneic (genetically not-identical) members of a given
      species, whereas a xenograft crosses species lines. Allografts and xenografts
      provoke a strong immunological response which, unless suppressed, leads to
      rejection and graft loss. Immunological processes involved in rejection include
      humoral (B-cell) and cellular (T-cell) components that are both antigen specific
      and non-specific. 45 years ago Peter Medawar and his colleagues established that
      rejection has an immunological basis. From studies of skin grafts between
      animals, they demonstrated that transplantation immunity was actively acquired,
      systemically propagated and highly specific. Previous exposure to donor antigens
      was shown to lead to the sensitization of the recipient and resulted in a
      markedly accelerated rejection upon re-exposure to the same antigens. Also at
      this time, the possibility of transplantation tolerance, or specific allograft
      unresponsiveness was first described in an animal bone marrow chimera model. The
      greatest challenge in clinical transplantation today is to develop in the organ
      recipient a state of immunologic non-responsiveness to the organ while preserving
      the ability for immune surveillance and function necessary for life. 

PMID- 25951557
TI  - Beta Cell Replacement Therapy in the 1990's An Overview of Pancreatic and Islet
      Cell Transplantation.
AB  - The goal of pancreatic beta cell replacement therapy is to restore normoglycemia
      in insulinopenic Type I diabetics patients. Pancreas transplantation is now
      considered a therapeutic option for Type I diabetic patients. It can no longer be
      considered an experimental procedure. Although a number of techniques have been
      applied in an attempt to restore normal glucose metabolism in Type I diabetic
      patients, pancreatic transplantation is the only therapy that consistently
      achieves normal glycosylated hemoglobin levels, an accomplishment rarely if ever
      achieved with frequent insulin injections or insulin pump therapy. Restoration of
      normoglycemia can be accomplished by either selectively transplanting isolated
      pancreatic islet cells or by transplanting the pancreas, usually as a composite
      graft of duodenum and whole pancreas. At this time, the likelihood of achieving
      independence from insulin is greater with a whole pancreas transplant than with
      an islet transplant. However, considerable progress in the field of islet
      transplantation has been made. This chapter will review the state of pancreas and
      islet transplantation. 

PMID- 25951558
TI  - Technical aspects of intestinal transplantation.
AB  - Since the advent of the potent immunosuppressive agent FK 506, intestinal
      transplantation has become a feasible therapeutic option for patients with
      irreversible intestinal failure. In this chapter, we present our clinical
      experience with intestinal transplantation, focusing on the technical aspects of
      both the donor and recipient operations. The logistics of the operative procedure
      have been described previously. 

PMID- 25951559
TI  - Human fetal surgery.
AB  - The ability to "see" the fetus before birth with routine obstetrical sonography,
      has changed the management of many congenital anomalies. Although most
      correctable malformations diagnosed prenatally, are best cared for by appropriate
      medical or surgical therapy after planned delivery at term, fetal intervention in
      selected cases may be advantageous. 

PMID- 25951560
TI  - Stereotactic core breast biopsy a replacement for surgical breast biopsy.
AB  - In 1988 two separate technologies were joined together by a team of radiologists
      in Denver, Colorado: a stereotactic breast biopsy system and an automated biopsy
      gun system. With the union of these two technologies, a new era in early breast
      cancer diagnosis began, stereotactic core breast biopsy. Any lesion that can be
      seen by mammography can be accurately biopsied with the stereotactic core breast
      biopsy. The accuracy of the procedure depends upon highly developed mammography
      skills and is, consequently, an advanced radiology procedure. Accuracy is equal
      to or greater than accuracy with traditional localization and open, surgical
      breast biopsy. 

PMID- 25951561
TI  - An update on mammography.
AB  - For at least 7 degrees % of breast cancers there are no known causal factors
      other than gender and aging. Other possible risk factors include hormonal,
      genetic, nutritional, morphologic, environmental (chemical, pesticides, food
      additives), irradiation, and viruses. Japanese women have much less breast cancer
      than women in the U.S.A., and after age 45, their incidence levels off or falls,
      whereas ours continues to rise. Furthermore, within a generation or two of moving
      to the U.S.A., Japanese women have a similar incidence to ours! What are we doing
      that increases our risk for this disease? It would certainly suggest that the
      other risk factors are involved and much research continues to explore this.
      Screening with mammography and breast physical examination is the cornerstone of
      earlier detection, improved survival and reduced mortality from breast cancer. A
      variety of studies and improvement in stage trends support this. Despite this,
      overall mortality from breast cancer remains unchanged. However, increasing
      incidence with stable mortality would suggest there is some reduction in overall
      mortality. Some other reasons for no reduction in overall mortality include: I.
      The variable biological forms and natural history of the disease. Assuming an
      average 100 days doubling time, cancer has been present in a woman's breast if
      not elsewhere for 6-7 years or longer before it is potentially detectable by
      mammography or breast physical examination. The extent of disease, cell type and
      grade, and host resistance are all important survival factors. Not enough breast
      cancers are at an early stage when diagnosed and treated. Not enough eligible
      women are being routinely screened with optimum mammography and breast physical
      examination. There is too much reliance on breast self-examination and breast
      physical examination alone for detection. 

PMID- 25951562
TI  - Chemotherapy and hormonal therapy for breast cancer.
AB  - Significant incremental advances in the use of systemic hormonal therapy and
      chemotherapy for the treatment of breast cancer have occurred in the past few
      years. Benefits of systemic therapy can be broadly divided into two major
      categories. The first is the favorable impact of systemic adjuvant therapy on
      recurrence and survival following primary surgical therapy for early stage
      disease. In this setting, both hormonal therapy and chemotherapy are effective.
      The results of recent trials as well as an overview analysis of randomized
      studies, have been able to further delineate, although not unequivocally, for
      which populations of patients a given type of therapy is most efficacious.
      Additionally, a more precise estimate of the reduction in odds of relapse and
      death afforded by a given therapy and within a defined patient subgroups is now
      possible, and these may be helpful in guiding clinical decision-making. Second,
      the treatment of advanced metastatic disease remains challenging due to the
      inability to induce long-term remissions or cures despite common initial
      responsiveness to hormonal therapy or chemotherapy. Over the last decade, only a
      few new drugs have been approved for the treatment of breast cancer, although
      several promising chemotherapeutic and biological agents are under scientific and
      clinical development. The use of therapy in this setting is therefore currently
      aimed at improving symptoms and quality of life. The use of conventional and
      novel chemotherapeutic agents at escalated doses with the use of hematopoietic
      growth factors, peripheral stem cells or autologous marrow support in terms of
      improved response rates and the potential to prolong survival, achieve long-terms
      remissions or cures, and improve quality of life is under active investigation. 

PMID- 25951563
TI  - Intraoperative radiotherapy experimental and clinical results, future prospects.
AB  - During the last two decades increasingly complex surgical techniques have been
      developed to improve the resection rate in the surgical treatment of cancer.
      There is an enormous growth in the development of new chemotherapeutic agents,
      and in the insight in chemotherapy treatment regimens. Since growth factors
      became available, high dose intensive chemotherapy combined with autologous bone
      marrow transplant can be performed with a low morbidity and mortality rate.
      Within radiation oncology technical advances in methods of radiation therapy,
      including the use of computerized planning (3D) treatment and conformal treatment
      have decreased the radiation-induced morbidity. To increase the radiation effect,
      e.g. to improve local control, without increasing radiation toxicity, hyper
      fractionation, radiation-sensitizers, and radiation-protectors were clinically
      investigated. New radiation techniques and equipment like brachytherapy (BT)
      units and intraoperative radiotherapy (IORT) became available. All these new
      techniques are today also used in the treatment of cancer as a combined modality
      treatment, with the idea to improve the local control rate, the disease free-,
      and overall survival without increasing or inducing treatment morbidity, and more
      over to prevent multilating surgical procedures. 

PMID- 25951564
TI  - Immunotherapy for cancer.
AB  - The study of the immune system on the cellular and molecular level has made
      significant strides over the past several decades. The role of immune system
      against infection is self-evident. Although the role of the immune system in the
      immune surveillance of cancer has not been proven, the immune system is believed
      to play an interactive role in the regulation of tumor growth. Immunotherapy is
      the application of the immune system to fight against the tumor. Although
      immunotherapeutic approaches have been tried in many types of cancer, both
      malignant melanoma and renal cell carcinoma seem to show occasional, but
      definitive response to immunotherapy. The fact that immune eradication of tumor
      is most efficient when the tumor burden is minimal speaks for the fact that
      immunotherapy may be most effective for control of microscopic disease.
      Therefore, to maximize the effect of immunotherapy, the tumor burden needs to be
      reduced, hopefully to microscopic level either by surgery or in combination with
      chemotherapy and radiation therapy. Also, new strategies are needed to develop
      more potent vaccines and stimulate effector cells to eradicate tumor cells under
      the most optimal conditions. 

PMID- 25951565
TI  - Current treatment of primary tumors of the liver in Japan.
AB  - The number of patients dying from primary malignant tumors of the liver in Japan
      has steadily increased during the last two decades. There are several
      epidemiological and clinical characteristics of primary malignant tumors of the
      liver in Japan, among which are: (I) hepatocellular carcinomas (hepatomas) which
      comprise approximately 90% of the cases; (2) high association of hepatoma with
      viral hepatitis and with consequent liver cirrhosis (over 85%); and (3) male
      predominance (5-6 to 1 male-to-female ratio). In recent years, more and more
      smaller hepatomas are being detected due to the efficient and liberal use of
      ultrasonography on high risk patients, and hepatic resections of limited extent
      such as segmentectomy and subsegmentectomy are now becoming increasingly common
      surgical procedures. This article will present an overview of current status of
      treatment of patients with hepatoma in Japan, and the information contained may
      prove to be useful for clinical management of Western patients, though some of
      their epidemiological features differ significantly from those of Japanese
      patients. 

PMID- 25951566
TI  - Development and testing of a bioartificial liver.
AB  - Management of patients with acute severe liver failure is a major clinical
      challenge. We need to understand better normal and abnormal liver physiology,
      develop methods of assessing the degree of liver dysfunction, standardize methods
      of intervention and develop rational procedures to support the acutely failing
      liver until it either recovers or is replaced. Investigators have attempted to
      support animals and patients with liver insufficiency, utilizing various
      extracorporeal support systems including cross-circulation, whole liver blood
      perfusion, hemadsorption, hemodialysis, plasma exchange, total body wash-out, use
      of microsomal enzymes bound to artificial carriers and other. None of these
      therapeutic modalities succeeded in gaining wide clinical acceptance. Charcoal
      hemoperfusion has been used to treat severe acute liver failure with mixed
      results. Although there is clear experimental evidence that the technique has
      some beneficial effects, a controlled prospective clinical study failed to
      demonstrate significant clinical advantages. Other methods which relied primarily
      upon blood detoxification, showed limited success as well. Thus it appears that,
      at least for now, whole organ transplantation remains the only method with
      clinically-proven efficacy for treating severe acute liver failure. In attempting
      to develop systems for temporarily supporting patients until an organ becomes
      available for transplantation and because of the complexity and vast number of
      metabolic and other physiologic functions provided by the liver, it was felt that
      to provide effective ex vivo liver support, either utilization of whole organ
      perfusion or construction of a liver support system utilizing intact, viable,
      functioning isolated liver cells will be needed. 

PMID- 25951567
TI  - General surgery in the patient with AIDS.
AB  - In 1993, it is estimated that 2 million Americans are infected with the human
      Immunodeficiency Virus (HIV). The Acquired Immune Deficiency Syndrome (AIDS)
      represents the most severe manifestation of infection with the virus. In the
      patient with AIDS, helper T lymphocytes are depleted resulting in a defect in
      cell mediated immunity. The resulting state of profound immunosuppression leads
      to susceptibility to rare infections and tumors. Although opportunistic
      infections have been seen in patients on immunosuppressive therapy, those
      associated with AIDS are much more severe and extensive. Many patients present
      with symptoms that mimic acute surgical emergencies. In other cases, the
      presentation has been one of a more chronic disease state. Some of the diseases
      associated with AIDS are directly attributable to the effects of the HIV virus.
      In all of these categories, there are some patients who will benefit from
      surgical therapy. In many cases medical therapy will be more appropriate. The
      evaluation of these patients can represent a major diagnostic challenge to the
      surgeon. A familiarity with these disease processes is essential for timely
      diagnosis and appropriate treatment. 

PMID- 25951568
TI  - Current use of substitute heart valves.
AB  - Although repair of diseased heart valves became possible in the 1940s,
      replacement of such valves had to await the development and refinement of the
      heart lung machine, as well as the advent of serviceable valve substitutes. Early
      investigators were hindered by the idea that alternative valves should closely
      resemble anatomic ones. Not until the early 1960s, with the introduction of caged
      ball prostheses by Harken and Starr, did effective valve replacement become
      possible. Since that time, substitute heart valves have continued to evolve, and
      many improvements have been made in their design and fabrication. As of 1988,
      approximately 51,000 valves were being implanted annually in the United States. 

PMID- 25951569
TI  - Cardiopulmonary perfusion.
AB  - Open heart surgery is one of the most highly technical of all modern medical
      techniques, and includes procedures such as coronary artery bypass grafting,
      cardiac valve repair or replacement, correction of congenital defects, resection
      of aneurysms, ablation of abnormal pathways of conduction, etc. It relies on the
      coordinated interaction of a heart surgeon, an anesthesiologist, several nurses
      and technicians, and a perfusionist. The first successful open heart surgery was
      performed in Philadelphia forty years ago by Dr. John Gibbon, Jr., whose wife,
      Mary, was his perfusionist. This historical landmark came after two decades of
      laboratory exploration and perfection of their extracorporeal circuit and its
      ability to sustain life. Perfusion, the technology which has evolved from those
      groundbreaking discoveries, controls, supports and maintains the circulation by
      application of extracorporeal devices. During open-heart surgery, perfusion
      (cardiopulmonary bypass - CPB) supplants the functions of the heart and lungs to
      provide the surgeon with a still, dry operating field. Today, this highly
      specialized role is performed by individuals conversant in a variety of
      scientific modalities working in close communication and cooperation with the
      surgeon. Perfusionists understand the anatomy, pathology, and physiology of the
      patient, while administering medications, anesthetics, blood, blood components
      and blood substitutes. Simultaneously, they operate a highly sophisticated
      electromechanical device to substitute for the human heart and lungs. Today's
      perfusionists know and utilize aspects of varied pursuits which include a
      functional comprehension of machines and motors, electronics and electrical
      safety, plastics and biocompatibility, drugs and pharmacology, blood and its
      components, hemodynamics and fluid dynamics, hypothermia and hyperthermia, gas
      exchange and metabolism, electrolytes and blood compatibility, anticoagulation
      and anesthesia. The logarithmic expansion in these unrelated fields of study have
      enhanced our ability to provide patient care. 

PMID- 25951570
TI  - Heart transplantation.
AB  - Since the first human heart transplantation performed by Barnard on December 3,
      1967, cardiac transplantation has now largely entered its third decade of
      clinical applicability. Up to the end of the seventies, the rather disappointing
      survival results mainly caused by the limited effectiveness of the
      immunosuppression therapy available at that time, maintained the clinical use of
      the procedure to a restricted number of no more than 20 to 30 patients each year
      world wide. The introduction in 1980 of Cyclosporine in the immunosuppression
      therapy has produced a tremendous improvement in the survival rate and has since
      promoted a spectacular resurgence of interest for heart transplantation which is
      presently a well established therapy for end stage congestive heart failure.
      Indeed, currently the real limiting factor of the treatment is the limited
      procurement of donor organs. 

PMID- 25951571
TI  - Progress on the total artificial heart.
AB  - The total artificial heart (TAH) is a device that fully replaces the failing
      heart and provides control of the circulatory system. This device has been used
      to provide permanent support, however, its most important role is to serve as a
      bridge to cardiac transplantation. There are two of these devices available: the
      CardioWest C-70TM (Symbion, Jarvik J-7TM) and the Penn State Heart. The TAH
      replaces the ventricles and is anastomosed to the respective atria and great
      vessels. It is constructed of segmental polyurethane and utilizes mechanical
      heart valves for inflow and outflow. It connects to a console via drive lines
      that pierce the skin, The TAH is pneumatically driven, and a personal computer
      monitors its function. Its advantages include control of the circulatory system,
      reversal of early organ failure, and early mobility of the patient. Its
      disadvantages include cost, and the complications of infection and
      thromboembolism. Further investigation of this device is required to develop an
      optimal total artificial heart. 

PMID- 25951572
TI  - High speed rotational atherectomy in coronary artery disease.
AB  - Despite major advances in its diagnosis and management, coronary artery disease
      remains the major cause of death accounting for 45.3 percent of all deaths in the
      United States. One of the major milestones in the treatment of coronary artery
      disease has been the introduction of non-surgical revascularization in the form
      of percutaneous transluminal coronary angioplasty by Andreas Gmentzig in 1977. In
      the early years, PTCA could only be performed in proximal, discrete, non
      calcified lesions. Over the last decade, major advances in the catheter, balloon
      and guide wire technology as well as increased operator experience extended the
      benefits of PTCA to patients with more complex lesions and multivessel coronary
      artery disease. Although the initial impetus for the development of newer devices
      has been to address the problem of restenosis, they are proving to be useful in
      treating lesions that are inadequately treated or subject to increased incidence
      of complications. The high speed rotational atherectomy is a valuable addition
      with its ability to treat long, calcified lesions. This report will describe the
      technical aspects of the Rotablator(r), the procedure of high speed rotational
      atherectomy and its clinical applications. 

PMID- 25951573
TI  - New laser and angioscopic technologies in medicine.
AB  - The goal of this chapter is to describe the evolution and implementation of
      several new interventional technologies which expand the capabilities for less
      invasive coronary artery intervention. These technologies, including excimer
      laser angioplasty and angioscopy, are based on the use of new fiberoptics and
      laser technology. While the application of these technologies may appear
      unrelated, each specialty has borrowed technology and techniques from other
      disciplines to develop less invasive forms of therapy. 

PMID- 25951574
TI  - Pulmonary arteriovenous malformations: transcatheter embolization.
AB  - The congenital abnormality of the pulmonary vessel's development, presented by a
      direct communication between pulmonary artery and pulmonary veins, has multiple
      pathomorphologic manifestations which lead, in turn, to a wide range of anomalies
      such as pulmonary arteriovenous malformations (PAVM), pulmonary arteriovenous
      aneurysms (PAVA), pulmonary arteriovenous fistulas, pulmonary angiomas, cavernous
      hemangiomas and pulmonary-hamartomas (Rozenstrauch et al. 1987: Burke et a1.
      1986). 

PMID- 25951575
TI  - Intravascular stents for the treatment of venous obstruction.
AB  - Intravascular stents were primarily designed for use in the arterial system,
      however, there are many venous disorders that may be effectively treated with
      these devices. Indeed, they have been placed throughout the venous system to
      treat venous obstruction. Stents have been used in superior vena cava syndrome,
      catheter induced stenoses of central veins; most commonly subclavian veins, and
      stenoses of arterio-venous fistulae to name a few common sites. Another major
      application of stents in the venous system has been in the creation of
      transjugular intrahepatic portosystemic shunts (TIPs) for the treatment of portal
      hypertension. There are reports of stents being used to treat obstructive hepatic
      venous webs (Budd-Chiari Syndrome), May-Thurner Syndrome, and even in the veins
      of the central nervous system. As experience and follow-up with stents increase,
      new venous applications will be reported. 

PMID- 25951576
TI  - Techniques and technology in endovascular surgery.
AB  - Today's vascular surgeons are no longer confined to the time-honored progressive
      triad of exercise, medication, and bypass surgery for the treatment of peripheral
      vascular disease. Our options have expanded to include primary therapy using
      thrombolysis, laser angioplasty, atherectomy, balloon dilation, and intravascular
      stents, most of these tecnological categories featuring several devices from
      which to select. Coupled with the concomitant development of intraluminal
      assessment and guidance technologies, namely, intravascular ultrasound (IVUS) and
      angioscopy, today's vascular specialists can evaluate atherosclerotic disease
      with greatly enhanced accuracy, deriving far more specific information about an
      obstruction than was ever required for classical vascular reconstruction. In the
      end, this new specialty of endovascular surgery will provide results equal to
      those methods used in the past but with less invasiveness. All these options and
      a more complex diagnostic database require coordination if these new resources
      are to be used to their fullest advantage for maximal revascularization. It is
      now incumbent upon vascular surgeons to appreciate the strategies for selecting
      endovascular interventions based upon lesion pathology and desired outcome. 

PMID- 25951577
TI  - Current treatment and prevention of pulmonary embolus with the greenfield filter.
AB  - Anticoagulation is standard therapy for treatment of venous thromboembolic
      disease. However, in some cases it is unsafe or ineffective. Mechanical
      interruption of the inferior vena cava (IVC) with the Greenfield filter offers
      the best level of mechanical protection for these patients. Commonly accepted
      indications for filter insertion are listed in (Figure 1). The original 24 F
      stainless steel Greenfield vena caval filter (SGF) has been in use for more than
      20 years and a smaller 12 F titanium (TGF-MH) version has been approved for
      clinical use. The unique geometry of the six-legged conical design allows
      adequate flow within the IVC even when 70% of the cone is filled with thrombus
      (Figure 2). Each filter has demonstrated a high rate of caval patency and low
      rate of recurrent PE. 

PMID- 25951578
TI  - Vascular Prosthetics: the Gore-Tex ePTFE Stretch Graft.
AB  - Following introduction of the Gore-Tex stretch vascular graft in 1991, over
      15,000 bifurcated and 35,000 straight grafts have been distributed (Figure I).
      This novel graft, recommended for arterial and venous reconstruction, is touted
      to afford significantly superior handling characteristics, kink-resistance and
      conformability. In addition, the "stretch" feature is thought to confer ease of
      sizing and anastomotic accuracy. Whether this product of advanced polymer science
      represents a panacea in the field of vascular grafting or a mere addition to the
      host of less than ideal synthetic conduits remains to be discerned. The first
      human implantation of a stretch graft was conducted by one of the authors
      (R.T.G.) during aortic replacement at the Eastern Virginia Medical School (EVMS).
      A favorable experience has since been gained by utilization of the stretch graft
      during vascular reconstruction for aortoiliac, infrainguinal and visceral
      arterial disease. This review will present the intriguing history of synthetic
      graft development and recount our experience with the Gore-Tex stretch vascular
      graft. 

PMID- 25951579
TI  - The medial visceral rotation approach to the proximal abdominal aorta: how to
      assemble and use the omni-tract(r) retractor system.
AB  - Debakey, Creech and Morris were the first to report that unrestricted exposure of
      the distal thoracic and entire abdominal aorta could be achieved by a
      thoracoabdominal approach with rotation of the viscera from left to right in a
      plane anterior to the left kidney. Approximately ten years later, Shirkey and
      colleagues described the technique of transabdominal medial visceral rotation in
      a plane anterior to the left kidney to expose an injury to the proximal superior
      mesenteric artery. Shortly thereafter, Buscaglia, Blaisdell and Lim reported
      their experience in treating 46 patients with penetrating abdominal vascular
      injuries. They advocated the use of left to right medial rotation of the viscera
      to approach the aorta and its branches and the use of right to left medial
      rotation of the viscera to approach the inferior vena cava. They also described
      modifying the approach, by rotating the left kidney anteriorly and medially to
      access the posterolateral aorta. Subsequently, transabdominal medial visceral
      rotation became a popular approach for the treatment of traumatic injuries to the
      proximal abdominal aorta. The first published description of this approach in the
      elective sitting came from Crawford who used it to expose complex aneurysms
      involving the paravisceral and pararenal aorta. 

PMID- 25951580
TI  - Monitoring Distal Extremity Perfusion with the Pulse Amplitude Monitor during
      Vascular Reconstruction.
AB  - One problem in vascular surgery today is the effective monitoring of blood flow
      to distal extremities before, during, and after a surgical reconstruction.
      Current methods of blood flow assessment such as periodic pulse palpation, skin
      signs, Doppler sounds, and capillary refill are neither continuous nor
      objectively comparable. Because of the qualitative nature of these methods, it is
      difficult to compare measurements taken by different people at different times,
      making a quick and appropriate response to changing perfusion requirements
      difficult. In order to address these problems, a system has been designed to
      monitor and document pulse amplitudes non-invasively. A pulse amplitude monitor
      system (Figure 1) consists of a pulse sensor and a waveform monitor (Impra,
      Tempe, AZ). The sensor (Figure 2) contains a piezoelectric film which is used to
      detect the slight mechanical oscillations of the arterial wall beneath the skin
      surface. This film is mounted on a compressible foam block which isolates the
      vibrations and maintains constant force on the skin. The sensor is taped over a
      distal pulse, typically that of the dorsalis pedis. 

PMID- 25951581
TI  - Postoperative Salvage: Technological Advance in the "Washed vs Unwashed" Blood
      Controversy.
AB  - In the past decade, the standard of care for transfusion in major surgery has
      evolved in most modern hospitals to auto transfusion (AT) techniques. In several
      states, in fact, it has become a law of "informed consent". The surgeon must
      present the risks of homologous transfusion and discuss alternatives and options
      with the patient. Presently, three standard transfusion options are preoperative
      donation, intraoperative salvage, and postoperative salvage. This article will
      address aspects of the latter option - post-operative salvage. Present technology
      has made significant advances over older collection systems. The Haemolite(r) 2
      is a compact, portable cell-saver well-suited for this purpose for reasons to be
      presented. Postoperative blood salvage is not a new concept. The Sorenson Device
      (Sorenson Research Co., Salt Lake City, UT) has been used extensively for many
      years to collect blood from mediastinal and chest tubes following cardiovascular
      and thoracic surgery. Similarly, the Soleotrans collection device (Solco-Basle,
      Rockland, Mass) has been used in vascular and orthopedic cases for blood salvage.
      Other devices such as the Pleura-Vac and Auto-Vac share the same features:
      collection of shed blood in low volume, filtration, and reinfusion without
      washing the RBC's. (Figure I) The omission of this processing step is the major
      difference in comparison with the Haemolite(r) 2 that separates the RBC's by
      centrifugal washing. (Figure 2) Presently this "washed vs unwashed" aspect is the
      source of controversy, which this article will attempt to clarify. 

PMID- 25951582
TI  - Retroperitoneal approach to the aorta.
AB  - Most historians feel that history is cyclical and, indeed, circular. The
      retroperitoneal approach for aortic level surgery emphasizes this phenomenon.
      Although there has been a great deal of interest in this "new" method, it is
      truly an old approach. Sir Astley Cooper ligated a high lying iliac artery
      aneurysm through this approach in the early 1800's, while Dulsost reported
      resection of an abdominal aortic an aneurysm with a homograft replacement
      achieved through this approach in 1952. In 1963, Rob reviewed 500 of his patients
      who underwent the retroperitoneal approach for aortic surgery and
      enthusiastically advocated this approach, because of its lower morbidity and
      mortality. Unfortunately little hard data accompanied this paper. Ten years
      later, a large series of 90 patients who underwent aortoiliac reconstruction was
      reviewed by Helsby, et a1. 1975. In this series he employed a long left
      paramedian incision to achieve this retroperitoneal exposure of the aorta. A low,
      3%, mortality was reported. More recently, Melvin Williams at Johns Hopkins
      reawakened interest in the retroperitoneal approach when he described a 4%
      operative mortality accompanying difficult aortic reconstruction. He favored
      medial rotation of the left kidney so that the aorta could be approached
      posteriorly. His seminal report of an exceedingly low mortality and morbidity,
      despite complex aortic anatomy influenced the readoption of this approach by
      several surgeons. Influenced by his results we adopted the retroperitoneal
      approach for high risk AAA while Leather and Sicard subsequently reported large
      series of aortoiliac reconstruction and aneurysms done through this approach.
      These series were associated with a relatively low mortality and shortened
      hospital stay (Table I). 

PMID- 25951583
TI  - Vascular Imaging: Overview Where Is This Technology Leading? What's the Best Bet
      for the Future?
AB  - New and exciting vascular imaging technologies are assuming increasingly
      important roles in the management of vascular disease. Non-invasive modalities
      such as computerized tomography, magnetic resonance imaging and duplex ultrasound
      supplement the information obtained by invasive techniques including angiography,
      angioscopy and intraluminal ultrasound. This paper outlines the modem and
      developing vascular imaging techniques that are rapidly becoming integral
      components of advanced diagnostic systems as well as therapeutic devices. 

PMID- 25951584
TI  - Hemodialysis access techniques.
AB  - Progression in hemodialysis technology and vascular access techniques has led to
      many patients remaining on chronic hemodialysis for significantly greater periods
      of time. The surgically constructed arteriovenous fistula at the wrist, mid
      forearm, or antecubital fossa presents the most ideal and long-term angioaccess.
      Adequate radial or brachial arterial flow is mandatory for success, and moderate
      to large sized patent superficial arm veins are even more critical for immediate
      and long-term patency. A properly selected and constructed fistula has primary
      patency rates often exceeding five and ten years. Only 15 percent of the chronic
      renal failure population are candidates for arteriovenous fistula (autogenous)
      angioaccess. This percentage is significantly lower in the acutely ill
      hospitalized individuals who become semiurgent hemodialysis candidates.
      Resultantly, arteriovenous placement of a non-autogenous expanded PTFE graft has
      become the modern day mainstay for long-term chronic access construction. 

PMID- 25951585
TI  - Ultrasound Guided Balloon Angioplasty: What is its Role?
AB  - A modified angioplasty catheter has been developed which can be guided-into
      position with duplex ultrasound. This reduces the risks of ionizing radiation and
      contrast agents and uses a modality familiar to the vascular surgeon. This
      catheter was tested successfully in a canine model for safety, accuracy and
      therapeutic efficacy. Following FDA approval, clinical trials in humans were
      initiated. This paper describes the preliminary results with use of this device
      in humans. 

PMID- 25951586
TI  - Intraoperative transesophageal echocardiography.
AB  - A methodical, basic intraoperative transesophageal exam can be performed quickly
      by anesthesiologists trained in transesophagea1 echocardiography. This provides a
      wealth of information with minimal invasiveness that is useful for the
      anesthesiologist, surgeon, and internist involved in the patient's care.
      Transesophageal echocardiography (TEE) is particularly valuable in the
      intraoperative monitoring of ventricular volume, ischemia and evaluation of valve
      morphology. And, as TEE imaging improves it is rapidly replacing aortography as
      the gold standard in the rapid evaluation of aortic dissection. 

PMID- 25951587
TI  - Body contouring.
AB  - Body contour surgery concerns the correction of diverse morphological
      abnormalities of the body which may occur due to various acquired and congenital
      etiologies. The concept of surgical body sculpting has achieved widespread
      recognition and acceptance because it safely alters such deformities yielding
      functionally aesthetic results. Several factors account for the current
      popularity of body contouring. Foremost among them, is the considerably increased
      exposure of the body which is seen in most modem cultures, particularly in warm
      climates. In no other period in the history of western civilization have men and
      women been so revealingly attired. In addition, today's competitive society
      strongly encourages the maintenance of a lean athletic body, as a symbol of good
      health, youth and vigor. The reality of achieving this physical ideal becomes
      increasingly less likely because of current sedentary lifestyles and dietary
      excesses. These factors combine to create a disturbing disequilibrium between an
      individual's desired condition and his actual state. Regular adherence to proper
      diet and exercise must be stressed, but unfortunately some of these deformities
      remain resistant to the most sincere of such efforts. Subsequently, there are
      increasingly greater numbers of people who seek surgical correction for specific
      abnormalities. Body contour surgery is also an important reconstructive tool in
      the correction of extremely lax skin in obese patients who have recently
      undergone dramatic weight loss. 

PMID- 25951588
TI  - The skin tumor: a reconstructive challenge.
AB  - The type of reconstruction performed following skin tumor surgery is directly
      related to the type, extent, and site of the skin tumor. The skin tumors with
      which the plastic surgeon is most often confronted are the basal and squamous
      cell cancers and melanoma. It is well documented that the incidence of these
      tumors are increasing at an alarming rate. This is believed to be primarily due
      to excessive sun exposure and the thinning of the protective ozone layer. Under
      these circumstances, the plastic surgeon today must be well equipped to not only
      treat these tumors, as well as other rarer diseases, but also to reconstruct the
      sometimes challenging resulting defects. The guiding reconstructive principle is
      as Ralph Millard admonished: Replace lost tissue with like tissue. A skin graft
      at the tip of the nose can be very distracting due to its patch-like, depressed
      appearance. In contrast, a full-thickness skin flap would allow the
      reconstructive "material" to blend in with its surroundings for a more impressive
      result. The plastic surgeon has several items in his armamentarium to assist in
      the execution of this principle. Some of the techniques are based on age-old
      ideas, while others represent very recent, almost revolutionary advances. These
      advances include: 1. The introduction of the tissue expander: This concept has
      allowed the plastic surgeon to reconstruct defects that would would have normally
      required disfiguring skin grafts or free tissue transfers. 2. The elucidation of
      the vascular supply to the skin and underlying muscles and fascia: This knowledge
      has endowed the plastic surgeon with a tremendous pallet of reliable flaps to
      reconstruct a particular defect. 

PMID- 25951589
TI  - TRAM Flap Breast Reconstruction.
AB  - The transverse rectus abdominus musculocutaneous flap, or TRAM flap, has
      revolutionized the plastic and reconstructive surgeon's approach to breast
      reconstruction. Since its first clinical description by Hartrampf, Schellan, and
      Black in 1982, the TRAM flap has become today's standard for autogenous tissue
      breast reconstruction. In light of the recent controversy regarding silicone
      breast implants, the use of autogenous tissue for breast reconstruction has
      become even more popular. It is the wide belief of most plastic and
      reconstructive surgeons that, by using autogenous tissue, the reconstructed
      breast has a more natural shape and contour. Furthermore, patient satisfaction is
      extremely high and problems inherent with implants, such as capsular contracture,
      are avoided. With newer technology and a stronger emphasis on self-examination
      and routine mammographic screening, breast cancer is currently being detected at
      earlier stages. Because of this, more and more women with diagnosed breast cancer
      are undergoing breast conserving surgery and radiotherapy. Patients with larger
      tumors, in more advanced stages, often require a more extensive operation, namely
      a modified radical mastectomy. The TRAM flap, in an immediate or delayed setting,
      is an ideal technique for the reconstruction of a modified radical mastectomy
      defect. We at the Breast Care Center of Mount Zion Medical Center of U.C. San
      Francisco are extremely pleased with the results of immediate breast
      reconstruction using the TRAM flap techniques. 

PMID- 25951590
TI  - Treatment of scoliosis in the adult.
AB  - With the increasing awareness in both the medical community, as well as the
      general public of the progressive nature of adult scoliosis, more patients with
      this condition are coming to the attention of the spinal surgeon. With recent
      technical developments, the surgical armamentarium currently available has
      certainly improved, yet these patients remain a challenging population of
      patients. Infantile, juvenile, and adolescent idiopathic scoliosis are defined by
      their age of presentation. Similarly, adult scoliosis is defined as a
      presentation of scoliosis after skeletal maturity. Yet most studies in the
      literature define adult scoliosis arbitrarily as scoliosis existing in a patient
      age 18 or older. The majority of these patients, therefore, have curves which
      have persisted through adolescence into adult life with etiologies which mirror
      those of a younger patient population. Degenerative scoliosis related to
      osteoporosis and iatrogenic causes are additional etiologies of deformity which
      more typically present in adult patients. The indications for treatment in the
      adult patient are similar to those in the adolescent: progression of the
      deformity, pain, deterioration of pulmonary function, and perhaps cosmesis. The
      complications encountered during the surgical management of these patients is
      quite high (50-80%) when compared to their adolescent counterparts. Complications
      include pseudoarthrosis, loss of lumbar lordosis, thromboembolic disease,
      instrumentation failure, neurologic deficits, and wound infections. Therefore,
      even with the recent advances in surgical technique the decision of whether or
      not to operate on a given patient remains the single most critical decision. 

PMID- 25951591
TI  - Instrumentation of the occipital-atlantal-axial (c0-c1-c2) complex.
AB  - Few areas of spinal surgery present a greater challenge than management of
      occipitocervical abnormalities. This is due to the simultaneous presence of two
      commanding, yet conflicting treatment principles. First, decompression and
      protection of the spinal cord at this level is synonymous with the presevation of
      life itself. Second, however, the degree of cervical movements at this junction
      is unprecedented in the spine, requiring the preservation movement yet
      stabilization of discrete motion segemnts. The interrelation of these two
      critical functions is realized in the complex arrangement of the C0- C1-C2
      anatomic configuration. The occipitocervical junction is responsible for 50% of
      the 90 degrees of head rotation. In addition, 10-15 degrees of flexion and
      extension are added to the subaxial cervical spine by C0-C1-C2.This duality of
      function is the primary reasin for the complexity of the facet joints in this
      location. No lateral bending occurs at this level. 

PMID- 25951592
TI  - Subaxial cervical spine.
AB  - Instrumentation techniques in the cervical spine were first described in 1891.
      Over 100 years have passed, and many surgeons have made contributions that now
      allow complicated operations to be performed with predictable results for many
      conditions affecting the cervical spine. The purpose of this chapter is to
      describe the currently acceptable techniques of instrumentation and fusion for
      the subaxial cervical spine. Because different devices are used, depending on
      whether the spine is approached from the front or from the back, this chapter is
      divided into those used through anterior and those used through posterior
      approaches. The decision to approach a given problem anteriorly or posteriorly
      depends on several factors including the location of the pathology, the nature of
      the underlying problem, the goals of the operation, and the experience of the
      surgeon. 

PMID- 25951593
TI  - Skeletal fixation of the lumbar spine.
AB  - Low back pain is a large and increasing cause of workers compensation claims in
      all industrialized nations. In the United States, 23% of all compensation claims
      involved back pain. Almost 90% of these were self limiting sprains and strains.
      It has been estimated that the remaining 10% account for approximately 75% of
      lost work days, medical costs and permanent disability payments. It is the goal
      of the spine surgeon to provide the patient with relief from his symptoms and
      return him or her to the work place. Advances in lumbar skeletal fixation have
      increased the fusion rate, decreased hospital stay and immobilization and
      decreased morbidity associated with lumbar spinal fusions. 

PMID- 25951594
TI  - Pulsed electromagnetic fields: an adjunct to interbody spinal fusion surgery in
      the high risk patient.
AB  - Lumbar fusion success rates are unpredictable. Turner, reporting on 82 published
      studies, cites a fusion success rate that ranged from 16% to 93%, mean 66%.
      Spinal fusion can be compromised by a number of risk factors that have been
      identified which tend toward a poorer prognosis. These risk factors include
      smoking, graft type (autograft vs. allograft), and number of fusion levels. Brown
      reports a statistically different, 32% decrease in spinal fusion healing in
      smokers as compared to nonsmokers. Allograft has been reported to significantly
      lower success rate in posterolateral fusions. Autograft is the preferred graft
      material because it is both tissue compatible and contains viable bone cells. If
      these bone cells can continue to be viable during the bridging process, the
      fusion healing process should be enhanced. Allograft bone does not have any
      viable bone cells within its matrix and may be rejected due to tissue
      incompatibility issues. Wilkinson reported that each additional fusion level
      decreased the possibility of spinal fusion success by approximately 20%. Surgeons
      are attempting various treatment regimens and adjunctive procedures to increase
      the odds of fusion for these high risk patients. One method is through the
      adjunctive use of electrical stimulation by pulsed electromagnetic fields (PEMFs)
      following a spinal fusion procedure. PEMFs is an inductive method of generating
      an electric potential at the fusion site. A pulsing magnetic field surrounding
      the fusion site through a dual coil system creates an electronegative potential
      along the fusion site. This negative potential is very similar to the natural
      property that bone has of healing itself. This technology has proven useful in
      treating the nonunion of long bone and it seemed reasonable to attempt to improve
      fusion success rates in spinal fusions given the relative safety of PEMFs and the
      success noted so far in long bones. The purpose of this paper is to demonstrate
      the safety and efficacy of PEMFs in treating spinal fusion patients with one or
      more high risk factors regardless of the presence/absence of fixation. 

PMID- 25951595
TI  - Spinal endoscopy: the history, evolution, and applications.
AB  - History and development: As we continue to better define the true indications of
      surgical procedures and ultimately refine these procedures to improve their
      inherent morbidity, the development of spinal endoscopic techniques continue to
      enhance minimally invasive surgical procedures. Surgeons desire to define anatomy
      and to visualize pathology long preceded our ability to utilize sophisticated
      imaging techniques. Visualization tools using rod-lens technology have been
      employed for use in the intracranial and in the myeloscopic visualization of
      neuroanatomy. Pool in 1942 described a large series of myeloscopic inspections of
      intrathecal normal and abnormal anatomy. His classic diagrams display the
      presence of disc herniations, arachnoiditis, and spinal stenosis from intrathecal
      inspections performed through a large bore myeloscope ( Figure 1 ). The continued
      evolution of myeloscopy was thought to be essential for the treatment of
      arachnoiditis, large herniated disc disease, and intrathecal tumor pathology. Its
      complications, however, led to its disuse because of the large bore scope
      requirements and the morbidity required to insert this instrumentation in the
      appropriate neural cavity. 

PMID- 25951596
TI  - Outpatient laparoscopic lumbar discectomy: description of technique and review of
      first twenty-one cases.
AB  - Economic and clinical factors have placed an increasing emphasis on minimally
      invasive surgical treatment of lumbar disc herniations. Percutaneous
      posterolateral techniques have been used increasingly over the last seven years
      but have definite technical limitations related to location of the disc
      herniation and its size. Dissatisfaction with percutaneous posterolateral lumbar
      discectomy (PPLD) led the senior author to explore the possibility of an anterior
      approach. Preliminary work included a "hands on" laparoscopy course and assisting
      experienced laparoscopists in the operating room. Before authorization from the
      Palomar Medical Center Investigational Review Board was obtained, dissection of
      the prevertebral space was performed in a human volunteer and a two level
      discectomy on a recently deceased patient was carried out in the operating room.
      The first operation was performed on February 4, 199I. Early in the series,
      patient selection was identical to that of percutaneous posterolateral
      discectomy, namely a soft posterolateral herniation contained within the
      posterior longitudinal ligament (PLL). As experience was gained, indications were
      expanded to include larger disc herniations. A description of the technique and
      our experience with the initial 21 consecutive cases form the basis of this
      report. 

PMID- 25951597
TI  - Robotic systems in surgery.
AB  - Computer-driven robots and medical imaging technology may soon enable surgeons to
      plan and execute intricate procedures with unprecedented precision. Our
      experience in introducing a robotic system for use in an active role in
      cementless total hip replacement surgery has convinced us that the marriage of
      these two technologies-robotics and medical imaging-is likely to change the way
      many types of surgical procedures are performed. The ability to link an image
      based preoperative plan with its surgical execution by a robot may be the key to
      improved outcomes. Research and development of robotic systems for a wide variety
      of medical applications is underway at a number of prestigious institutions.
      Grenoble University has developed the IGOR (Imaged Guided Operating Robot)
      system. This six-axis robot has performed more than 400 interventions, acting as
      a positioner for brain surgery in both biopsy and therapeutic procedures.
      AlephMed and Digital are currently assisting the developers in integrating image
      analysis into the system. Future development plans include an application for
      spinal surgery. 

PMID- 25951598
TI  - Ceramics in orthopedic surgery.
AB  - Inorganic ceramic compounds have found increasing serviceability as implants in
      orthopedic surgery and can be classified into general categories using their
      chemical property characteristics. These characteristics include terms, such as
      inert, active, and degradable, that normally refer to the ceramics, time
      dependent interactions on a relative basis, one-to-another, when implanted in
      hard and soft tissue sites. The early interest in the high grade (purity and
      strength) oxide ceramics of aluminum (alumina), titanium [titania], and zirconium
      (zirconia) was based on information from industrial applications in chemical
      processing of corrosive solutions. The selection of alumina for high surface area
      (porous) implants in bone was based partly upon the knowledge that these ceramic
      materials could maximally resist biodegradation phenomena, while being routinely
      available at reasonable costs. 

PMID- 25951599
TI  - Premise for bioresorbable materials in joint replacement arthroplasty.
AB  - Total joint replacement arthroplasty has been extremely successful since its
      inception in the 1960's. There have been untoward problems however that have
      become more apparent with the current state of the art joint replacement. These
      problems include thigh pain following total hip replacement arthroplasty,
      proximal bone resorption as a result of stress shielding, and areas of bone
      lysis. The progressively enlarging size of the metal implant stem with its
      associated increased elastic modulus has been implicated in the above noted
      problems. The implant stem as well as metal alloy screws utilized to fix
      acetabular and tibial plate components to bone have been suggested to contribute
      to particulate debris and the above noted problems through fretting.
      Bioresorbable polymers can be utilized as screws to fix the definitive implant to
      bone as well as utilized as a stem to allow rigid fixation of the implant until
      there is firm attachment, whether by mechanical or chemical bonding. When the
      definitive implant has been adequately attached to bone, the resorbable polymer
      degrades completely, thereby, obviating many of the problems seen with the
      presently retained screws and large, high modulus, intramedullary stems. 

PMID- 25951600
TI  - Lasers in orthopedic surgery.
AB  - Among surgical specialities; orthopedics has been the slowest to embrace the
      laser as a surgical tool. Although lasers have been used in ophthalmology for
      over two decades, and laser usage has become commonplace in gynecology,
      otorhinolaryngology, dermatology, plastic surgery, and general surgery, it is
      only within the past four years that lasers have attracted appreciable attention
      in orthopedics. The fact that much of the surgery in the majority of specialities
      is ablative in nature makes use of the laser particularly appealing, as lasers
      are the ultimate of ablative tools. Much of orthopedic surgery, on the other
      hand, is primarily reparative or reconstructive in nature. The re-establishment
      of continuity or the replacement of tissues such as bone, tendon, and ligament
      are the goals of the majority of orthopedic surgical procedures. While lasers may
      ultimately play some role in tissue repair, that role is currently viewed as one
      of providing precision (for example, nerve and small vessel "welding") rather
      than strength, the latter being crucial in orthopedics. It is, thus, not
      surprising that the interest in "orthopedic lasers" centers around the relatively
      few procedures that are ablative in nature - intervetebral disc removal, the
      removal of polymethylmethacrylate, and the majority of arthroscopic procedures. 

PMID- 25951601
TI  - Shoulder arthroscopy: surgical technique.
AB  - Arthroscopic techniques for shoulder arthroscopy have evolved and been refined
      constantly over the last decade. Significant advances have been made, compared to
      the first arthroscopic intraarticular examinations on cadavers by Takagi in 1918.
      Advances in fiberoptics, computer technology, and surgical instrumentation,
      coupled with innovative ideas and improved operative skills, have opened a new
      era in the orthopedic evaluation of intraarticular structures and treatment of
      pathology by the orthopedic surgeon. Arthroscopic examination of the glen humeral
      joint and sub acromial bursa permits the surgeon to visually assess, document,
      and treat shoulder pathology in an injury specific manner. Critical to effective
      use of this technology and skill is a comprehensive and reproducible system for
      thorough examination and documentation, so that no abnormality is inadvertently
      overlooked and treatments are effectively performed. In this fashion,
      standardization is developed for evaluating surgical treatments and providing a
      common base for professional communication and continued education within the
      orthopedic community. At the Southern California Orthopedic Institute, a
      comprehensive 15-point glenohumeral and 8-point subacromial examination from both
      posterior and anterior portals has been developed and is widely accepted in most
      arthroscopic forums. The operating room set-up, instrumentation, patient
      positioning, and the authors' preference for systematic glenohumeral arthroscopy
      and bursoscopy will be described. Specific methods for-arthroscopic subacromial
      decompression, distal clavicle resection, and evaluation of the rotator cuff will
      be outlined. It is imperative that the surgeon have a complete knowledge of
      normal shoulder anatomy and common variants. 

PMID- 25951602
TI  - Hip arthroscopy.
AB  - The indications for performing arthroscopy of the hip are fewer than for the knee
      and shoulder. Yet, it is a very useful procedure when the occasion arises. The
      purpose of this article is to present a technique that is simple and safe. The
      lateral approach over the greater trochanter, not only meets these criteria, but
      it gives the surgeon enough maneuverability to completely visualize the joint and
      to perform surgery. 

PMID- 25951603
TI  - The Ilizarov method.
AB  - While the use of external fixators is not revolutionary, the Ilizarov apparatus
      has dramatically improved the application of the principles of external fixation
      to the management of bony defects, malunions, infections, and pseudarthroses.
      Since its formal introduction in Western Siberia in 1951 by Gavril Abramovich
      Ilizarov, an international cadre of surgeons has employed its methods to pioneer
      modern limb salvaging procedures. Such techniques are made possible by the
      numerous advantages, including immediate loading of the limb postoperatively, and
      the use of healthy viable bone to replace devascularized dead bone "in situ" by
      osteoclasis, localized transport and osteogenesis. Accordingly, leg length
      discrepancy, deformity and infected nonunions may all be treated effectively. The
      basic premise of the llizarov technique is that osteogenesis can occur at a
      surgical osteotomy site given the appropriate degree of retained vascularity,
      fixation and quantified distraction. This dogma is a function of many variables
      which Ilizarov classified into three categories; biological, clinical, and
      technical. First, biologic variables include preservation of endosteal and
      periosteal blood supply via corticotomy and stable fixation to prevent shear
      forces, but to permit axial dynamization with postoperative weight bearing.
      Distraction should occur at approximately 1 mm. per day divided into four times
      per day. At the termination of distraction, neutral fixation should be permitted
      to allow strengthening of the new bone. In essence, the technique fools the body
      into believing it is a child again. The corticotomy sites now act as physes. 

PMID- 25951604
TI  - Assessment of heat shock protein 70 induction by heat in alfalfa varieties and
      constitutive overexpression in transgenic plants.
AB  - Heat shock proteins (HSPs) are molecular chaperones involved in many cellular
      functions. It has been shown that mammalian cytosolic HSP70 binds antigenic
      peptides mediating the activation of the immune system, and that it plays a
      determining role in tumour immunogenicity. This suggests that HSP70 may be used
      for the production of conjugated vaccines. Human and plant HSPs share high
      sequence similarity and some important biological functions in vitro. In
      addition, plant HSPs have no endotoxic side effects. Extraction of HSP70 from
      plants for use as vaccine adjuvant requires enhancing its concentration in plant
      tissues. In this work, we explored the possibility to produce HSP70 in both
      transgenic and non-transgenic plants, using alfalfa as a model species. First, a
      transcriptional analysis of a constitutive and an inducible HSP70 genes was
      conducted in Arabidopsis thaliana. Then the coding sequence of the inducible form
      was cloned and introduced into alfalfa by Agrobacterium-mediated transformation,
      and the accumulation of the protein in leaf tissue of transgenic plants was
      demonstrated. We also tested diverse alfalfa varieties for heat-inducible
      expression of endogenous HSP70, revealing variety-specific responses to heat
      shock. 

PMID- 25951605
TI  - Enhancing inhibition-induced plasticity in tinnitus--spectral energy contrasts in
      tailor-made notched music matter.
AB  - Chronic tinnitus seems to be caused by reduced inhibition among frequency
      selective neurons in the auditory cortex. One possibility to reduce tinnitus
      perception is to induce inhibition onto over-activated neurons representing the
      tinnitus frequency via tailor-made notched music (TMNM). Since lateral inhibition
      is modifiable by spectral energy contrasts, the question arises if the effects of
      inhibition-induced plasticity can be enhanced by introducing increased spectral
      energy contrasts (ISEC) in TMNM. Eighteen participants suffering from chronic
      tonal tinnitus, pseudo randomly assigned to either a classical TMNM or an ISEC
      TMNM group, listened to notched music for three hours on three consecutive days.
      The music was filtered for both groups by introducing a notch filter centered at
      the individual tinnitus frequency. For the ISEC-TMNM group a frequency bandwidth
      of 3/8 octaves on each side of the notch was amplified, additionally, by about 20
      dB. Before and after each music exposure, participants rated their subjectively
      perceived tinnitus loudness on a visual analog scale. During the
      magnetoencephalographic recordings, participants were stimulated with either a
      reference tone of 500 Hz or a test tone with a carrier frequency representing the
      individual tinnitus pitch. Perceived tinnitus loudness was significantly reduced
      after TMNM exposure, though TMNM type did not influence the loudness ratings.
      Tinnitus related neural activity in the N1m time window and in the so called
      tinnitus network comprising temporal, parietal and frontal regions was reduced
      after TMNM exposure. The ISEC-TMNM group revealed even enhanced inhibition
      induced plasticity in a temporal and a frontal cortical area. Overall, inhibition
      of tinnitus related neural activity could be strengthened in people affected with
      tinnitus by increasing spectral energy contrast in TMNM, confirming the concepts
      of inhibition-induced plasticity via TMNM and spectral energy contrasts. 

PMID- 25951606
TI  - Renal function and coronary microvascular dysfunction in women with
      symptoms/signs of ischemia.
AB  - OBJECTIVES: Chronic kidney disease (CKD) is more prevalent among women and is
      associated with adverse cardiovascular events. Among women with symptoms and
      signs of ischemia enrolled in the Women's Ischemia Syndrome Evaluation (WISE), a
      relatively high mortality rate was observed in those with no obstructive coronary
      artery disease. Coronary microvascular dysfunction or reduced coronary flow
      reserve (CFR) was a strong and independent predictor of adverse outcomes. The
      objective of this analysis was to determine if renal function was associated with
      coronary microvascular dysfunction in women with signs and symptoms of ischemia.
      METHODS: The WISE was a multicenter, prospective, cohort study of women
      undergoing coronary angiography for suspected ischemia. Among 198 women with
      additional measurements of CFR, we determined the estimated glomerular filtration
      rate (eGFR) with the CKD-EPI equation. We tested the association between eGFR and
      CFR with regression analysis. RESULTS: The median eGFR was 89 ml/min. The eGFR
      correlated with CFR (r = 0.22; P = 0.002). This association persisted even after
      covariate adjustment. Each 10-unit decrease in eGFR was associated with a 0.04
      unit decrease in CFR (P = 0.04).There was a strong interaction between eGFR and
      age (P = 0.006): in those >=60 years old, GFR was strongly correlated with CFR (r
      = 0.55; P<0.0001). No significant correlation was noted in those <60 years old.
      CONCLUSIONS: Reduced renal function was significantly associated with lower CFR
      in women with symptoms and signs of ischemia. Coronary microvascular dysfunction
      warrants additional study as a mechanism contributing to increased risk of
      cardiovascular events in CKD.

PMID- 25951609
TI  - Graded hypoxia acts through a network of distributed peripheral oxygen
      chemoreceptors to produce changes in respiratory behaviour and plasticity.
AB  - Respiratory behaviour relies critically upon sensory feedback from peripheral
      oxygen chemoreceptors. During environmental or systemic hypoxia, chemoreceptor
      input modulates respiratory central pattern generator activity to produce reflex
      based increases in respiration and also shapes respiratory plasticity over longer
      timescales. The best-studied oxygen chemoreceptors are undoubtedly the mammalian
      carotid bodies; however, questions remain regarding this complex organ's role in
      shaping respiration in response to varying oxygen levels. Furthermore, many taxa
      possess distinct oxygen chemoreceptors located within the lungs, airways and
      cardiovasculature, but the functional advantage of multiple chemoreceptor sites
      is unclear. In this study, it is demonstrated that a distributed network of
      peripheral oxygen chemoreceptors exists in Lymnaea stagnalis and significantly
      modulates aerial respiration. Specifically, Lymnaea breath frequency and duration
      represent parameters that are shaped by interactions between hypoxic severity and
      its time-course. Using a combination of behaviour and electrophysiology
      approaches, the chemosensory pathways underlying hypoxia-induced changes in
      breath frequency/duration were explored. The current findings demonstrate that
      breath frequency is uniquely modulated by the known osphradial ganglion oxygen
      chemoreceptors during moderate hypoxia, while a newly discovered area of
      pneumostome oxygen chemoreception serves a similar function specifically during
      more severe hypoxia. Together, these findings suggest that multiple oxygen
      chemosensory sites, each with their own sensory and modulatory properties, act
      synergistically to form a functionally distributed network that dynamically
      shapes respiration in response to changing systemic or environmental oxygen
      levels. These distributed networks may represent an evolutionarily conserved
      strategy vis-a-vis respiratory adaptability and have significant implications for
      the understanding of fundamental respiratory control systems. 

PMID- 25951607
TI  - Intestinal parasite infections in symptomatic children attending hospital in Siem
      Reap, Cambodia.
AB  - BACKGROUND: Infections with helminths and other intestinal parasites are an
      important but neglected problem in children in developing countries. Accurate
      surveys of intestinal parasites in children inform empirical treatment regimens
      and can assess the impact of school based drug treatment programmes. There is
      limited information on this topic in Cambodia. METHODS: In a prospective study of
      intestinal parasites in symptomatic children attending Angkor Hospital for
      Children, Siem Reap, Cambodia, April-June 2012, samples were examined by
      microscopy of a direct and concentrated fecal sample. Two culture methods for
      hookworm and Strongyloides stercoralis were employed when sufficient sample was
      received. Demographic, clinical and epidemiological data were collected.
      PRINCIPAL FINDINGS: We studied 970 samples from 865 children. The median (inter
      quartile range) age of the children was 5.4 (1.9-9.2) years, 54% were male. The
      proportion of children with abdominal pain was 66.8%, diarrhea 34.9%, anemia
      12.7% and malnutrition 7.4%. 458 parasitic infections were detected in 340
      (39.3%) children. The most common parasites using all methods of detection were
      hookworm (14.3%), Strongyloides stercoralis (11.6%) and Giardia lamblia (11.2%).
      Giardia lamblia was most common in children aged 1-5 years, hookworm and
      Strongyloides stercoralis were more common with increasing age. Hookworm,
      Strongloides stercoralis and Giardia lamblia were more common in children living
      outside of Siem Reap town. In a multivariate logistic regression increasing age
      was associated with all three infections, defecating in the forest for hookworm
      infection, the presence of cattle for S. stercoralis and not using soap for
      handwashing for G. lamblia. CONCLUSIONS/SIGNIFICANCE: This study confirms the
      importance of intestinal parasitic infections in symptomatic Cambodian children
      and the need for adequate facilities for laboratory diagnosis together with
      education to improve personal hygiene and sanitation.

PMID- 25951608
TI  - Integrated analysis of transcriptome in cancer patient-derived xenografts.
AB  - Patient-derived xenograft (PDX) tumor model is a powerful technology in
      evaluating anti-cancer drugs and facilitating personalized medicines. Multiple
      research centers and commercial companies have put huge efforts into building PDX
      mouse models. However, PDX models have not been widely available and their
      molecular features have not been systematically characterized. In this study, we
      provided a comprehensive survey of PDX transcriptome by integrating analysis of
      58 patients involving 8 different tumors. The median correlation coefficient
      between patients and xenografts is 0.94, which is higher than that between
      patients and cell line panel or between patients with the same tumor. Major
      differential gene expressions in PDX occur in the engraftment of human tumor
      tissue into mice, while gene expressions are relatively stable over passages. 48
      genes are frequently differentially expressed in PDX mice of multiple cancers.
      They are enriched in extracellular matrix and immune response, and some are
      reported as targets for anticancer drugs. A simulation study showed that
      expression change between PDX and patient tumor (6%) would result in acceptable
      change in drug sensitivity (3%). Our findings demonstrate that PDX mice represent
      the gene-expression and drug-response features of primary tumors effectively, and
      it is recommended to monitoring the overall expression profiles and drug target
      genes in clinical application. 

PMID- 25951610
TI  - Intramandibular glands in different castes of leaf-cutting ant, Atta laevigata
      (Fr. Smith, 1858) (Formicidae: Attini).
AB  - Intramandibular glands have been poorly studied in polymorphic ants, where the
      differences between castes were unsufficiently scrutinized. Leaf-cutting ants
      possess one of the most complex systems of communication and labor division,
      which is polymorphic well as age polyethism, and makes them an ideal model for
      the study of intramandibular glands. This study has investigated the occurrence
      of intramandibular glands in female castes and subcastes of Atta laevigata. The
      mandibles of the queen, medium, and minor workers, and soldiers were submitted to
      histological, histochemical, ultrastructural, and morphometric analyses. The
      class-3 gland cells and the epidermal gland with a reservoir were found in all
      the castes. The queens and soldiers showed a higher number of class-3 gland
      cells, distributed within the mandible as well as a greater gland size in
      comparison to the workers. The histochemical tests, periodic acid-Schiff (PAS),
      mercury-bromophenol, and Nile blue, were similar for the class-3 gland cells and
      epidermal glands with a reservoir. However, the tests evidenced differences
      between the castes, with carbohydrates strongly positive in all of them, whereas
      neutral lipids were found in the queen and soldiers. The protein was weakly
      positive in the queen, whereas in the soldier, medium, and minor workers these
      reactions were strongly positive in the intramandibular glands. Our findings in
      A. laevigata suggest that intramandibular glands are directly involved in labor
      division and consequently in chemical communication between the castes.

PMID- 25951612
TI  - From carbanions to organometallic compounds: quantification of metal ion effects
      on nucleophilic reactivities.
AB  - The influence of the metal on the nucleophilic reactivities of indenyl metal
      compounds was quantitatively determined by kinetic investigations of their
      reactions with benzhydrylium ions (Ar2 CH(+) ) and structurally related quinone
      methides. With the correlation equation log k2 =sN (N+E), it can be derived that
      the ionic indenyl alkali compounds are 10(18) to 10(24) times more reactive
      (depending on the reference electrophile) than the corresponding
      indenyltrimethylsilane. 

PMID- 25951611
TI  - Application of flow sensitive gradients for improved measures of metabolism using
      hyperpolarized (13) c MRI.
AB  - PURPOSE: To develop the use of bipolar gradients to suppress partial-volume and
      flow-related artifacts from macrovascular, hyperpolarized spins. THEORY AND
      METHODS: Digital simulations were performed over a range of spatial resolutions
      and gradient strengths to determine the optimal bipolar gradient strength and
      duration to suppress flowing spins while minimizing signal loss from static
      tissue. In vivo experiments were performed to determine the efficacy of this
      technique to suppress vascular signal in the study of hyperpolarized [1
      (13)C]pyruvate renal metabolism. RESULTS: Digital simulations showed that in the
      absence of bipolar gradients, partial-volume artifacts from the vasculature were
      still present, causing underestimation of the apparent reaction rate of pyruvate
      to lactate (kP). The addition of a bipolar gradient with b = 32 s/mm(2)
      sufficiently suppressed the vascular signal without a substantial decrease in
      signal from static tissue. In vivo results corroborate digital simulations, with
      similar peak lactate signal to noise ratio (SNR) but substantially different kP
      in the presence of bipolar gradients. CONCLUSION: The proposed approach
      suppresses signal from flowing spins while minimizing signal loss from static
      tissue, removing contaminating signal from the vasculature and increasing kinetic
      modeling accuracy without substantially sacrificing SNR or temporal resolution.

PMID- 25951613
TI  - Megaduodenum associated with gastric strongyloidiasis.
AB  - Gastric strongyloidiasis and megaduodenum are rare diseases. Gastrointestinal
      (GI) strongyloidiasis has many clinical features. One of them is megaduodenum. We
      describe a case of a 32-years-old man who has come to us from an endemic area for
      Strongyloides stercoralis. He had had megaduodenum diagnosed in his childhood. We
      submitted him to two surgeries. He has recovered just after the second surgery, a
      Roux-en-Y partial gastrectomy. After that, his follow-up was uneventful and the
      patient has gained 10kg in weight. Histopathology confirmed gastric
      strongyloidiasis. In conclusion, if patients arrive from an endemic area of S.
      stercoralis and if they present GI symptoms or a previous diagnosis of
      megaduodenum, they must be considered for a histological evaluation for gastric
      strongyloidiasis. 

PMID- 25951614
TI  - Cocoon abdomen - A rare cause of intestinal obstruction.
AB  - INTRODUCTION: Sclerosing encapsulating peritonitis or abdominal cocoon is a rare
      condition of unknown etiology in which intestinal obstruction result from
      encasement of variable length of bowel by dense fibro collagenous membrane.
      PRESENTATION OF CASE: A case of young male is reported who presented with
      features of small bowel obstruction with tender mass in the right iliac fossa. CT
      scan suggested features of internal herniation. On exploration, he was found to
      have small intestine, large intestine, stomach and liver covered with a thick
      cocoon like membrane. The membrane was gently peeled off the small intestine. The
      patient recovered well and was discharged on an oral diet. DISCUSSION:
      Preoperative diagnosis of abdominal cocoon is difficult and most cases are
      discovered incidentally on laparotomy. Contrast enhanced computed tomography or
      barium meal may be helpful in preoperative diagnosis. Surgical treatment is the
      main stay of treatment for this condition. Simple removal of the membrane and
      lysis of the adhesions produces optimal outcome. Bowel resection is indicated
      only when the intestine is nonviable. CONCLUSION: A high index of suspicion and
      appropriate radiology can prevent 'surprises' and unnecessary bowel resection.
      Simple removal of the membrane gives a good outcome.

PMID- 25951615
TI  - Inhibitory effects of nitrite on the reactions of bovine carbonic anhydrase II
      with CO2 and bicarbonate consistent with zinc-bound nitrite.
AB  - Carbonic anhydrase (CA) is a zinc enzyme that catalyzes hydration of carbon
      dioxide (CO2) and dehydration of bicarbonate in red blood cells, thus
      facilitating CO2 transport and excretion. Bovine CA II may also react with
      nitrite to generate nitric oxide, although nitrite is a known inhibitor of the
      CO2 hydration reaction. To address the potential in vivo interference of these
      reactions and the nature of nitrite binding to the enzyme, we here investigate
      the inhibitory effect of 10-30 mM nitrite on Michaelis-Menten kinetics of CO2
      hydration and bicarbonate dehydration by stopped-flow spectroscopy. Our data show
      that nitrite significantly affects the apparent dissociation constant KM for CO2
      (11 mM) and bicarbonate (221 mM), and the turnover number kcat for the CO2
      hydration (1.467 * 10(6) s(-1)) but not for the bicarbonate dehydration (7.927 *
      10(5) s(-1)). These effects demonstrate mixed and competitive inhibition for the
      reaction with CO2 and bicarbonate, respectively, and are consistent with nitrite
      binding to the active site zinc. The high apparent dissociation constant found
      here for CO2, bicarbonate and nitrite (16-120 mM) are all overall consistent with
      published data and reveal a large capacity of free enzyme available for binding
      each of the three substrates at their in vivo levels, with little or no
      significant interference among reactions. The low affinity of the enzyme for
      nitrite suggests that the in vivo interaction between red blood cell CA II and
      nitrite requires compartmentalization at the anion exchanger protein of the red
      cell membrane to be physiologically relevant.

PMID- 25951616
TI  - Antimicrobial effects of a bioactive glass combined with fluoride or triclosan on
      Streptococcus mutans biofilm.
AB  - OBJECTIVE: The objective of this study was to investigate the antibacterial
      effects on a cariogenic biofilm of a bioactive glass (BAG) combined with either
      sodium fluoride (NaF) or triclosan (TCS). DESIGN: According to minimal
      bactericidal concentrations, 37.5mg/ml of BAG, 4.69 mg/ml of NaF, and 15.53
      MUg/ml of TCS solutions were prepared. When used alone, the three antimicrobial
      solutions were increased to double-dosage strength (2 MBC). The study contained
      the following experimental groups: group 1, BAG (2 MBC); group 2, NaF (2 MBC);
      group 3, TCS (2 MBC); group 4, BAG+NaF; group 5, BAG+TCS; group 6, control
      (saline). Streptococcus mutans biofilm was cultured with 0.1% sucrose
      anaerobically on 66 sterilized coverslips (1 * 1 cm(2)) for 24h uninterrupted.
      After 10 min of exposure to the experimental groups, the microbial kinetics,
      morphology, and viability of the S. mutans biofilms were assessed by evaluation
      of colony-forming units (CFUs), scanning electron microscopy (SEM), and confocal
      laser scanning microscopy (CLSM). RESULTS: BAG (2 MBC) used alone showed
      significantly stronger antibacterial effects than the other two antimicrobials
      used alone. The combination groups also displayed the same or greater biofilm
      inactivation effects as BAG (2 MBC) in the plate count test. SEM showed smaller
      stacks (towers) and fewer surrounding bacteria in groups BAG (2 MBC), BAG+NaF,
      and BAG+TCS. Confocal microscopy also determined higher live/dead ratios in
      groups NaF (2 MBC), TCS (2 MBC), and control than in groups BAG (2 MBC), BAG+NaF,
      and BAG+TCS. CONCLUSIONS: The combinations of BAG with either NaF or TCS enhanced
      the inactivation effects of BAG (2 MBC) on S. mutans biofilm, and these findings
      should be further investigated clinically for the control of dental biofilms.

PMID- 25951617
TI  - Simultaneous removal of PCDD/Fs and NOx from the flue gas of a municipal solid
      waste incinerator with a pilot plant.
AB  - The pilot-scale plant on the simultaneous removal of PCDD/Fs and NOx from the
      flue gas of a municipal solid waste incinerator is presented. In order to
      research the influence of temperature on the catalytic decomposition of PCDD/Fs
      and the selective catalytic reduction of NOx, the experiments were performed at
      220  degrees C, 260  degrees C, and 300  degrees C, and the congener profiles of
      PCDD/Fs for the samples collected at the inlet and outlet were illustrated.
      Noteworthy, the detailed congener distributions of PCDD/Fs in the gas-phase and
      particle-phase of the inlet and 300-outlet (decomposition temperature = 300 
      degrees C) samples are presented, and the removal efficiencies eta(g-I-TEQ) and
      eta(p-I-TEQ) reached to 94.94% and 99.67%, respectively. The effect of the SCR
      process on the removal of PCDD/Fs was also studied at a relatively low
      temperature of 220  degrees C. Additionally, the NOx emissions and the SCR
      efficiencies were investigated.

PMID- 25951618
TI  - Formation of dioxins on NiO and NiCl2 at different oxygen concentrations.
AB  - Model fly ash (MFA) containing activated carbon (AC) as source of carbon, NaCl as
      source of chlorine and either NiO or NiCl2 as de novo catalyst, was heated for 1h
      at 350  degrees C in a carrier gas flow composed of N2 containing 0, 6, 10, and
      21 vol.% O2, to study the formation of PCDD/Fs (dioxins) and its dependence on
      oxygen. The formation of PCDD/Fs with NiCl2 was stronger by about two orders of
      magnitude than with NiO and the difference augmented with rising oxygen
      concentration. The thermodynamics of the NiO-NiCl2 system were represented, X-ray
      absorption near edge structural (XANES) spectroscopy allowed to probe the state
      of oxidation of the nickel catalyst in the MFA and individual metal species were
      distinguished using the LCF (Linear combination fitting) technique: thus three
      supplemental nickel compounds (Ni2O3, Ni(OH)2, and Ni) were found in the fly ash.
      Principal Component Analysis (PCA) indicates that both Ni2O3 and NiCl2 probably
      played an important role in the formation of PCDD/Fs.

PMID- 25951619
TI  - Identification of metabolites of PSORALEAE FRUCTUS in rats by ultra performance
      liquid chromatography coupled with quadrupole time-of-flight tandem mass
      spectrometry analysis.
AB  - The fruit of Psoralea corylifolia (Psoraleae Fructus) is a traditional Chinese
      medicine (TCM), which has been used to prevent and treat vitiligo, psoriasis, and
      osteoporosis in China for thousands of years. Phytochemical investigation on
      Psoraleae Fructus, as well as some metabolism research focused on
      pharmacokinetics of several single compounds from this plant, has been reported.
      However, the effective material of Psoraleae Fructus is still unknown. In the
      present study, the metabolic fate of multiple components of Psoraleae Fructus in
      rats was investigated by ultra performance liquid chromatography coupled with
      quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS). Based on a
      three-step strategy, a total of 142 Psoraleae Fructus-related xenobiotics were
      identified or tentatively characterized in rat biofluids after oral
      administration of six representative single compounds and Psoraleae Fructus
      extract. All six different types of constituents of Psoraleae Fructus, including
      furocoumarin, coumestan, isoflavone, flavanone, chalcone and monoterpene phenol,
      could be absorbed into the circulation system. In addition, compared with the
      metabolism of six representative single compounds, different metabolic fate was
      observed after oral administration of Psoraleae Fructus extract, which indicated
      that the drug-drug interactions occurred when fed by multi-component herbal
      extract, and the investigations only focused on several main components were not
      sufficient to represent and reflect the overall efficacy of plants. The present
      study will be conducive to further pharmacological mechanism research on
      Psoraleae Fructus.

PMID- 25951621
TI  - Spin-orbit coupling and anomalous Josephson effect in nanowires.
AB  - A superconductor-semiconducting nanowire-superconductor heterostructure in the
      presence of spin-orbit coupling and magnetic field can support a supercurrent
      even in the absence of phase difference between the superconducting electrodes.
      We investigate this phenomenon-the anomalous Josephson effect-employing a model
      capable of describing many bands in the normal region. We discuss the geometrical
      and symmetry conditions required to have a finite anomalous supercurrent, and in
      particular we show that this phenomenon is enhanced when the Fermi level is
      located close to a band opening in the normal region.

PMID- 25951620
TI  - Quantitative three-dimensional analysis of poly (lactic-co-glycolic acid)
      microsphere using hard X-ray nano-tomography revealed correlation between
      structural parameters and drug burst release.
AB  - The objective of this study was to investigate the use of transmission hard X-ray
      nano-computed-tomography (nano-CT) for characterization of the pore structure and
      drug distribution in poly (lactic-co-glycolic acid) (PLGA) microspheres
      encapsulating bovine serum albumin and to study the correlation between drug
      distribution and burst release. The PLGA microspheres were fabricated using a
      double-emulsion method. The results of pore structure analysis accessed with nano
      CT were compared with those acquired by scanning electron microscopy (SEM) and
      confocal laser scanning microscopy (CLSM). Surface pore interconnectivity and
      surface protein interconnectivity were obtained using combined nano-CT and pixel
      analysis. The correlation between surface protein interconnectivity with the
      initial burst release across various tested formulations was also analyzed. The
      size, shape, and distribution of the pores and protein could be clearly observed
      in the whole microsphere using nano-CT, whereas only the sectional information
      was observed using SEM or CLSM. Interconnected pores and surface connected pores
      could be clearly distinguished in nano-CT, which enables the quantitative
      analysis of surface pore interconnectivity and surface protein interconnectivity.
      The surface protein interconnectivity in different formulations correlated well
      with the burst release at 5-10h. Nano-CT provided a nondestructive, high
      resolution, and three-dimensional analysis method to characterize the porous
      microsphere. 

PMID- 25951622
TI  - Using "big data" to capture overall health status: properties and predictive
      value of a claims-based health risk score.
AB  - BACKGROUND: Investigators across many fields often struggle with how best to
      capture an individual's overall health status, with options including both
      subjective and objective measures. With the increasing availability of "big
      data," researchers can now take advantage of novel metrics of health status.
      These predictive algorithms were initially developed to forecast and manage
      expenditures, yet they represent an underutilized tool that could contribute
      significantly to health research. In this paper, we describe the properties and
      possible applications of one such "health risk score," the DxCG Intelligence
      tool. METHODS: We link claims and administrative datasets on a cohort of U.S.
      workers during the period 1996-2011 (N = 14,161). We examine the risk score's
      association with incident diagnoses of five disease conditions, and we link
      employee data with the National Death Index to characterize its relationship with
      mortality. We review prior studies documenting the risk score's association with
      other health and non-health outcomes, including healthcare utilization, early
      retirement, and occupational injury. RESULTS AND CONCLUSIONS: We find that the
      risk score is associated with outcomes across a variety of health and non-health
      domains. These examples demonstrate the broad applicability of this tool in
      multiple fields of research and illustrate its utility as a measure of overall
      health status for epidemiologists and other health researchers.

PMID- 25951623
TI  - Reproduction of a higher-order circular harmonic field using a linear array of
      loudspeakers.
AB  - This paper presents a direct formula for reproducing a sound field consisting of
      higher-order circular harmonics with polar phase variation. Sound fields with
      phase variation can be used for synthesizing various spatial attributes, such as
      the perceived width or the location of a virtual sound source. To reproduce such
      a sound field using a linear loudspeaker array, the driving function of the array
      is derived in the format of an integral formula. The proposed function shows
      fewer reproduction errors than a conventional formula focused on magnitude
      variations. In addition, analysis of the sweet spot reveals that its shape can be
      asymmetric, depending on the order of harmonics.

PMID- 25951624
TI  - Vertebral artery injury caused by internal jugular vein catheterization: two case
      reports.

PMID- 25951625
TI  - [Hyperkinetic disorders in childhood and adolescence- an analysis of KinderAGATE
      2009-2012].
AB  - OBJECTIVE: This contribution evaluates the prevalence, medication use as well as
      age and sex distribution in inpatients with hyperkinetic disorders at the
      KinderAGATE hospitals for 2009-2012. METHOD: The age, sex, leading diagnosis,
      prescribed medication, and dosage of each patient were recorded anonymously twice
      a year. They provide an outstanding epidemiological basis for the observation of
      the actual situation in child and adolescent psychiatry. RESULTS: Compared to our
      patient collective, patients diagnosed with hyperkinetic disorders (25.5% Pat)
      were on average 2 years younger and received psychopharmacological treatment more
      often (statistically significant). Although male patients are dominant here
      (84.3% HPat, mean age 9.9 years vs. 15.7% HPat, 10.1 years), the same proportion
      of female and male patients received psychostimulant treatment (48.0% vs. 52.2%).
      Besides methylphenidate, amphetamine, and atomoxetine, the antipsychotics
      risperidone, pipamperone, and quetiapine were noticeably often prescribed.
      CONCLUSION: Methylphenidate remains the drug of first choice in the treatment of
      ADHD. There is an upward trend in the proportion of patients being treated with
      antipsychotics, though this is not statistically significant. Because of the
      discrepancy between the available evidence and prescription practice in child and
      adolescent psychiatry, there is still a great demand for studies regarding long
      term efficacy and side effects.

PMID- 25951626
TI  - [Thoughts of leading talents training of Chinese medical science and technology-
      a speech by academician CHEN Ke-ji at the Inauguration Ceremony of Guangdong
      Branch, China Academy of Chinese Medical Sciences (November 24, 2014)].

PMID- 25951627
TI  - [Problems of diagnosis and treatment of liver fibrosis cirrhosis by integrative
      medicine].

PMID- 25951628
TI  - [Thinking over several problems about integrative medicine].

PMID- 25951629
TI  - [Analysis and comparison of ancient anatomy in western and eastern world].

PMID- 25951630
TI  - [Treating ischemic stroke patients of deficiency of qi and yin syndrome and
      static blood obstructing collaterals syndrome by Yangyin Yiqi Huoxue Recipe: a
      clinical study of therapeutic effect].
AB  - OBJECTIVE: To observe the clinical effect of Yangyin Yiqi Huoxue Recipe (YYHR,
      the basic recipe of Yangyin Tongnao Granule) in treatment of ischemic stroke
      patients of deficiency of qi and yin syndrome (DQYS) and static blood obstructing
      collaterals syndrome (SBOCS). METHODS: Totally 312 patients were assigned to the
      control group (86 cases) and the treatment group (226 cases) using strati- fied
      randomized allocation method. Patients in the treatment group were treated with
      modified YYHR, while those in the control group took Xueshuan Xinmaining. The
      treatment course was 4 weeks for all. Constituent ratios of the acute stage and
      the recovery stage of DQYS and SBOCS and their complicated syndromes were
      observed in the two groups. Changes of the clinical curative effect, clinical
      symptoms integral, whole blood viscosity ratio, plasma viscosity ratio,
      hematocrit, erythrocyte sedimentation rate (ESR), total cho- lesterol (TC),
      triglyceride (TG), high density lipoprotein cholesterol (HDL-C), and low density
      lipoprotein cholesterol (LDL-C) were detected in the two groups before and after
      treatment. RESULTS: There was statistical difference in constituent ratios of the
      acute stage and the recovery stage of DQYS SBOCS and its complicated syndromes
      between the two groups (P < 0.01). DQYS and SBOCS was basic syndrome types of the
      two groups. The cured and markedly effective rate was 71.24%(161/226) in the
      treatment group and 43.02% (37/86) in the control group. The total effective rate
      was 91.15% (206/226) in the treatment group, higher than that of the control
      group (76.74%, 66/86) with statistical difference (P < 0.01). There was
      statistical difference in the clinical symptoms integral, whole blood viscosity
      ratio, plasma viscosity ratio, hematocrit, ESR, TC, TG,HDL-C, and LDL-C (P <
      0.05, P < 0.01). CONCLUSIONS: Symptoms of ischemic stroke patients could be
      improved by modified YYHR. Indices such as the whole blood viscosity, plasma
      viscosity ratio, hematocrit, ESR, abnormal metabolism of blood lipids were also
      significantly improved. Pathological changes of blood stasis induced by qi-yin
      deficiency exist in ischemic stroke patients, and DQYS and SBOCS were basic
      syndrome types.

PMID- 25951631
TI  - [Effect-of Angong Niuhuang Pill on Th1/Th2 of cerebral infarction patients of
      phlegm-heat obstructing orifices in China and Indonesia].
AB  - OBJECTIVE: To observe the effect of Angong Niuhuang Pill (ANP) on Thl/Th2 in
      cerebral infarction patients and to explore the mechanism of phlegm-heat
      obstructing orifices. METHODS: Re- cruited were 30 cerebral infarction patients
      of phlegm-heat obstructing orifices syndrome (PHOOS) both in China and Indonesia.
      They were assigned to 4 groups according to the use of ANP, the Chinese treatment
      group, the Indonesia treatment group, the Chinese control group, and the
      Indonesia control group. Patients in the two control groups received conventional
      treatment, while those in the two treatment group additionally took ANP for 30
      successive days. Their adverse reactions were observe, and levels of INF-gamma
      and IL-4 were detected. RESULTS: The INF-gamma level and the INF-gamma/IL-4 ratio
      significantly decreased, and the IL-4 level increased after treatment in the four
      groups with statistical difference (P < 0.05). Compared with the control group
      after treatment in the same country, the INF-gamma level and the INF-gamma/IL-4
      ratio were lower, and the IL-4 level was higher in the two treatment groups (P <
      0.05). Compared with the two Chinese groups, the INF-gamma level and the INF
      gamma/IL-4 ratio were higher, and the IL-4 level was lower in the two Indonesian
      groups (P < 0.05). There was no statistical difference in the post-treatment
      indices between the two treatment groups. CONCLUSIONS: ANP had moderating effect
      on Th1/Th2 in cerebral infarction pa- tients. Cerebral infarction patients of
      PHOOS might exist certain relation with Th1/Th2.

PMID- 25951632
TI  - [Treatment of early and mid-term primary biliary cirrhosis by Qingying Huoxue
      Decoction Combined ursodeoxycholic acid: a clinical observation].
AB  - OBJECTIVE To observe the clinical efficacy by Qingying Huoxue Decoction (QHD)
      combined ursodeoxycholic acid (UDCA) in treating patients with early and mid-term
      primary biliary cirrhosis (PBC). METHODS Totally 78 patients were randomly
      assigned to the treatment group and the control group, 39 in each group. All
      patients received basic treatment and took UDCA (at the daily dose of 13-15
      mg/kg). Patients in the treatment group took QHD, one dose per day. The treatment
      course for all was 6 weeks. Clinical efficacy, gamma-glutamyl transferase (gamma
      GGT), alkaline phospatase (ALP), TBIL, alanine aminotransferase (ALT), and
      aspartate transaminase (AST) were observed before and after treatment. RESULTS
      Totally 21 (53. 8%) patients obtained complete response in the treatment group,
      with statistical difference when compared with that of the control group (11
      cases, 30. 8%). Levels of GGT, ALP, ALT, AST, and TBIL decreased in the two
      groups after treatment (P < 0.01). Levels of ALP, GGT, and TBIL were obviously
      lower in the treatment group than in the control group (P < 0.05). CONCLUSIONS:
      QHD combined UDCA in treating early and mid-term PBC patients was superior to the
      effect of using UDCA alone. It also could improve patients' liver function.

PMID- 25951633
TI  - [Effect of acupuncture along affected meridian on the MME gene expression of
      migraine patients without aura of gan-yang hyperactivity syndrome].
AB  - OBJECTIVE: To observe the effect of acupuncture along affected meridian on the
      mem- brane metallo-endopeptidase (MME) gene expression of migraine patients
      without aura (MO) of Gan-yang hyperactivity syndrome (GYHS). METHODS: Totally 20
      MO patients of GYHS were randomly assigned to the acupoint group (acupuncture
      along affected meridian) and the non-acupoint group, 10 cases in each group.
      Needling was performed once per day for 10 consecutive days. Gene chip technology
      was used to obtain two sets of gene expression profiles and analyzed using Gene
      Ontology (GO). RESULTS: In the acupoint group, MME gene expression decreased
      after needling (P = 0.0023).That gene was rich in the beta-amyloid metabolic
      process (P = 3.16E-05) and the peptide metabolic process (P = 0.009612). Its
      expression was not seen in the non-acupoint group. CONCLUSION: The effect of
      point selection along affected meridian could be achieved possibly by regulating
      the MME gene expression.

PMID- 25951634
TI  - [Effect of acupuncture on early onset of SSRIs treating depressive disorder and
      related indicators of neuroimmunology].
AB  - OBJECTIVE: To observe the intervention effect of acupuncture on early onset of
      selec- tive serotonin reuptake inhibitors (SSRIs) in treating depressive
      disorder, and to study its effect on ser- um 5-HT and unbalanced inflammatory
      cytokines secreted by TH1/TH2. METHODS: Totally 90 patients with depressive
      disorder were randomly assigned to the drug control group (as the control group,
      45 cases) and the acupuncture combined drug treatment group (as the treatment
      group, 45 cases). All patients were treated for 4 consecutive weeks. Another 45
      healthy subjects were recruited as a healthy control group. The effect of
      acupuncture on early onset of SSRls in treating acute phase depressive disorder
      pa- tients was evaluated by HAMD score in the control group and the treatment
      group before treatment,and at weekends of the 1st, 2nd, and 4th week after
      treatment. Besides, their serum levels of 5-HT, IL-1beta and IL-6 (secreted by
      TH1), and IL-4 and IL-10 (secreted by TH2) were detected before treatment and
      after treatment at the weekend of the 4th week. RESULTS: Compared with the
      healthy control group,serum lev- els of 5-HT, IL-4, and IL-10 decreased in the
      two drug-treated groups before treatment (P < 0.01); serum levels of IL-1beta and
      IL-6 increased (P <0.01). Compared with before treatment in the same group, HAMD
      score decreased in the control group at weekends of the 2nd and the 4th week
      after treatment (P < 0.01); HAMD scores decreased in the treatment group at
      weekends of the 1st, 2nd, 3rd,and 4th week after treatment (P < 0.01); serum
      levels of 5-HT, IL-4, and IL-10 increased,serum levels of IL-1beta and IL- 6
      decreased in the two drug-treated groups after treatment (all P < 0.01). Compared
      with the control group at the same time point,HAMD scores decreased in the
      treatment group at weekends of the 1st, 2nd,3rd,and 4th week after treatment (P <
      0.01),serum levels of 5-HT, IL-4, and IL-10 increased (P < 0.05, P < 0.01), serum
      levels of IL-6 decreased (P < 0. 01). CONCLUSION: Acupuncture could accelerate
      early onset of SSRIs in treating acute phase depressive disorder, and effectively
      regulate serum 5-HT levels and inflammatory cytokines secreted by TH1/TH2.

PMID- 25951635
TI  - [Effect of electro-acupuncture on the spindle and oocytes quality in patients
      with PCOS].
AB  - OBJECTIVE: To observe the effect of electro-acupuncture (EA) treatment on the
      oocyte quality in polycystic ovarian syndrome (PCOS) patients undergoing in vitro
      fertilization-embryo transfer (IVF-ET). METHODS: Totally 217 PCOS patients
      undergoing IVF-ET were assigned to two groups by random digit table, the EA group
      (119 cases) and the control group (98 cases). All patients received long program
      ovarian hyperstimulation with gonadotropin-releasing hormone agonist. Patients in
      the EA group received EA treatment in the process of controlled ovarian
      hyperstimulation till the oocyte retrieval day. The position relation of the
      spindle to the polocyte, the number of retrieved oocytes, the fertilization
      rate,the cleavage rate,the high quality embryo rate, the ovarian hyperstimulation
      syndrome (OHSS) incidence rate, the clinical pregnancy rate, the early abortion
      rate, the gonadotropins (Gn) dose and time, levels of estradiol (E2),
      progesterone (P), and luteinizing hormone (LH) on the day of human chorionic
      gonadotropin (HCG) were observed between the two groups. RESULTS: The ratio of
      oocytes in which the meiotic spindle deviation angle was < 60 degrees to the all
      oocytes was obviously higher in the EA group than in the control group (P <
      0.05). The oocytes in which the meiotic spindle deviation angle was < 60 degrees
      was positively related to level of E2 on the HCG day and the high quality embryo
      rate (r = 0.19,P < 0.01). Compared with the control group, the high quality
      embryo rate increased significantly (P < 0.05), the dose and days of Gn decreased
      significantly (P < 0.05) in the EA group. The clinical pregnancy rate was
      improved by 8.36%. CONCLUSIONS: The spindle was positively correlated with the
      oocyte quality. EA could improve the quality of oocytes and the clinical
      pregnancy rate in PCOS patients undergoing IVF-ET.

PMID- 25951636
TI  - [Treatment of acute cholestatic hepatitis by Compound Yindan Decoction: a
      clinical observation].
AB  - OBJECTIVE: To observe the clinical efficacy of comprehensive Western medical
      treatment plus Compound Yindan Decoction (CYD) in treatment of acute cholestatic
      hepatitis (ACH). METHODS: Using randomized controlled study, 60 ACH patients in
      line with inclusive criteria were randomly assigned to the treatment group
      (treated by comprehensive Western medical treatment plus CYD) and the control
      group (treated by comprehensive Western medical treatment alone), 30 in each
      group. Scores for symptoms and levels of liver functions [total bilirubin (TBIL),
      direct bilirubin (DBIL), alkaline phosphatase (ALP), glutamyl transpeptidase
      (GGT), total biliary acid (TBA)] were observed before and after treatment.
      RESULTS: Compared with before treatment in the same group, total scores for
      symptoms decreased in the treatment group and the control group at the end of the
      1st and the 4th week after treatment (all P < 0.05). Compared with the control
      group, total scores for symptoms decreased in the treatment group at the end of
      the 1st week (P < 0.05). Compared with before treatment, serum levels of TBIL,
      DBIL, ALP, GGT, and TBA all decreased in the two groups at the end of the 4th
      week after treat- ment (P < 0.01). Compared with the control group, serum levels
      of TBIL, DBIL, ALP, GGT, and TBA all decreased in the treatment group at the end
      of the 1st and the 2nd week after treatment (P < 0.05). Compared with the control
      group, the average time for TBIL and DBIL decreasing to the level less than five
      times the normal value was significantly shorter in the treatment group (P <
      0.05). CONCLUSION: CYD could significantly improve clinical symptoms of ACH
      patients, decrease serum levels of TBIL and DBIL, reduce serum levels of ALP,
      GGT, and TBA, obviously improve cholestasis, and promote the recovery.

PMID- 25951637
TI  - [Intervention of berberine on lipid deposition in liver cells of non-alcoholic
      fatty liver disease rats induced by high fat diet].
AB  - OBJECTIVE: To explore the effect of berberine on lipid metabolism disorder and
      lipid deposition in liver cells of non-alcoholic fatty liver disease (NAFLD) rats
      induced by high fat diet. METHODS: After one week adaptable feeding, 45 SPF level
      male SD rats were randomly divided into 3 groups, the normal control group, the
      model group, and the berberine group, 15 in each group. Except those in the
      normal control group, all rats were fed with high fat diet to prepare NAFLD
      model. As for rats in the berberine group, Berberine Hydrochloride was
      administered by gastrogavage. HE staining and oil red O staining were performed
      to identify the model after 8 weeks. Hepatocytes were isolated, and their
      activities and purities were tested by Typan blue staining and flow cytometry
      (FCM). Serum levels of TC, TG, HDL-C, and LDL-C were detected using automatic
      biochemical analyzer. mRNA expression levels of LXRalpha and FAS in liver cells
      were analyzed by Real-time quantitative polymerase chain reaction (PCR). Protein
      levels of LXRalpha and FAS in liver cells were examined by Western blot. RESULTS:
      The NAFLD rat model was successfully established by high fat diet. The yields of
      purified liver cells in each rat were (6.0-7.5) x 10(8). The viability of
      isolated liver cells with purity over 90% (tested by FCM analysis) was higher
      than 95%. Compared with the normal control group,the expression of LXRalpha and
      FAS at mRNA and protein levels was higher in the model group (P < 0.01). Compared
      with the model group, the expression of LXRalpha and FAS at mRNA and protein
      levels was obviously down-regulated in the berberine group (P < 0.01).
      CONCLUSIONS: LXRalpha/FAS signaling pathway was one of important signaling
      pathways of NAFLD lipid metabolism disorders. Berberine could recover hepatocyte
      fatty deposits in NAFLD rats by adjusting the LXR/FAS signaling pathway of
      hepatocytes, which might be one of important mechanisms for fighting against
      NAFLD.

PMID- 25951638
TI  - [Intervention of Huayu Qutan Recipe on liver SREBP-2 signal pathway of
      hyperlipidemia rats of pi deficiency syndrome].
AB  - OBJECTIVE: To explore the intervention of Huayu Qutan Recipe (HQR) on liver SREBP
      2 signal pathway of hyperlipidemia rats of Pi deficiency syndrome (PDS). METHODS:
      Totally 100 SPF grade SD rats were randomly divided into the blank control group,
      the hyperlipidemia group, the hyperlipidemia treatment group, the PDS
      hyperlipidemia group, and the PDS hyperlipidemia treatment group, 20 in each
      group. Common granular forage was fed to rats in the blank control group. High
      fat forage was fed to rats in the hyperlipidemia group and the hyperlipidemia
      treatment group. Rats in the PDS hyperlipidemia group and the PDS hyperlipidemia
      treatment group were treated with excessive labor and improper diet for modeling.
      They were administered refined lard by gastrogavage (3 mL each time, twice per
      day) and fed with high fat forage on the odd days, and fed with wild cabbage
      freely on even days. The modeling lasted for 30 days. Rats in the hyperlipidemia
      treatment group and PDS hyperlipidemia treatment group were administered with
      Huayu Qutan Recipe (20 mL/kg) by gastrogavage, once a day, for 30 successive
      days. Levels of serum cholesterol (TC), triglyceride (TG), low density
      lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C),
      and serum amylase (AMY) were detected by automatic biochemical analyzer. D-xylose
      excretion rate was determined using phloroglucinol method. Morphological changes
      of liver and the lipid deposition in liver were observed using HE stain and oil
      red O stain respectively, mRNA and protein expression levels of 3-hydroxy-3
      methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7alpha-hydroxylase 1
      (CYP7A1), LDL-R, and sterol regulatory element binding protein-2 (SREBP-2) were
      detected using real time RT-PCR and Western blotting. RESULTS: Compared with the
      blank control group, serum levels of TC (1.84 +/- 0.19 mmol/L, 2.23 +/- 0.43
      mmol/L) and LDL-C (0.99 +/- 0.24 mmol/L, 1.13 +/- 0.56 mmol/L) were higher in the
      hyperlipidemia group and the PDS hyperlipidemia group, serum levels of HDL-C
      (0.41 +/- 0.66 mmol/L, 0.41 +/- 0.11 mmol/L) and AMY activities (351 +/- 45
      mmol/L, 153 +/- 30 mmol/L) were lower, and urinary D-xylose excretion rates were
      lower (26.9 +/- 2.1 ng/mL, 15.0 +/- 1.7 ng/mL) (all P < 0.05). Lipid deposition
      occurred in liver cells. Much fat vacuoles occurred in the cytoplasm. Expression
      levels of HMGCR, CYP7A1, LDL-R, and SREBP-2 mRNA and proteins in liver
      significantly decreased (P < 0.01). Compared with the hyperlipidemia group, serum
      levels of TC and LDL-C significantly increased (P < 0. 05), AMY activities and
      urinary D-xylose excre- tion rates significantly decreased in the PDS
      hyperlipidemia group (P < 0.01). A large amount of lipid deposition occurred in
      liver. The atrophy of liver cells was obviously seen. Expression levels of
      CYP7A1, LDL-R, and SREBP-2 mRNA and proteins in liver were significantly lower (P
      < 0.01, P < 0.05). Serum levels of TC and LDL-C significantly decreased (P <
      0.05), AMY activities and urinary D-xylose excretion rates significantly
      increased in the hyperlipidemia treatment group (P < 0.01). Expression levels of
      CYP7A1, LDL-R, and SREBP-2 mRNA and proteins in liver were significantly
      increased (P < 0.01, P < 0.05). Compared with the PDS hyperlipidemia group, serum
      level of TC significantly decreased (P < 0.05), HDL-C levels, AMY activities and
      urinary D-xylose excretion rates significantly increased in the PDS
      hyperlipidemia treatment group (P < 0.01),expression levels of CYP7A1, LDL-R, and
      SREBP-2 mRNA and proteins in liver were significantly increased (P < 0.01).
      Similar changes occurred in the two treatment groups. CONCLUSIONS: Pi deficiency
      exacerbates abnormal serum TC level and the lipid deposition in liver. These
      might be related to regulating expression levels of LDL-R, HMGCR, and CYP7A1
      genes in the SREBP-2 signal pathway. HQR could regulate this pathway to intervene
      abnormal metabolism of TC.

PMID- 25951639
TI  - [The mechanism of tenuigenin for eliminating waste product accumulation in
      cerebral neurons of Alzheimer's disease rats via ubiquitin-proteasome pathway].
AB  - OBJECTIVE: To explore the scavenging action of tenuigenin (TEN) on intracerebral
      amyloid beta protein (Abeta) aggregation and the abnormal phosphorylated tau
      protein and its mechanism in Alzheimer's disease (AD) rats' brain. METHODS:
      Abeta1-40 was injected into the right CA1 region hippocampus to establish the AD
      model. Successfully modeled rats were divided into the model group, the low,
      middle, high TEN group. Rats were administered with TEN (18.5, 37.0, 74.0 mg/kg)
      by gastrogavage. Besides, a sham-operation group was set up. Expression levels of
      Abeta1-40 and Tau p-Ser262 were detected by immunohistochemistry. Expression
      levels of ubiquitin (Ub) and Ub-protein ligase E3 were measured by Western
      blotting.The content of 26S proteasome was detected by ELISA. RESULTS:
      Immunohistochemical results showed that the number of Abeta and Tau p-Ser262
      positively reacted neurons significantly increased in model group, when compared
      with the sham-operation group (P < 0.01). Results of Western blot showed
      expression levels of ubiquitinated protein were up-regulated and those of Ub
      protein ligase E3 were down-regulated in the model group (P < 0.01). ELISA
      results showed that the content of 26S proteasome significantly decreased in AD
      rats' brain (P < 0.01). Compared with the model group, expression levels of
      Abeta1-40, Tau p-Ser262, and Ub significantly decreased; expression levels of Ub
      protein ligase E3 apparently increased; the content of 26S proteasome
      significantly increased in each TEN treatment group (P < 0.05, P < 0.01). Best
      effect was shown in 37.0 mg/kg and 74.0 mg/kg TEN groups. CONCLUSIONS: Ub
      proteasome pathway (UPP) participated in the occurrence of AD. TEN could
      obviously reduce intracere- bral Abeta1-40 accumulation and abnormal tau
      phosphorylation.

PMID- 25951640
TI  - [Effect of Yixintai Granule on mRNA and protein expression levels of AQP, in
      renal medulla of chronic heart failure rabbits].
AB  - OBJECTIVE: To explore the effect of Yixintai Granule (YG) on mRNA and protein
      expression levels of AQP2 in renal medulla of chronic heart failure (CHF)
      rabbits. METHODS: CHF rat model was established by ear marginal vein injection of
      adriamycin. Successfully modeled rabbits were divided into the model group, the
      high (8.4 g/kg), middle (4.2 g/kg), and low dose (2.1 g/kg) YG group, and the
      Furosemide group (2 mg/kg). Besides, a normal control group was set up. Equal
      volume of physiological saline was administered to rabbits of the model group and
      the normal control group by gastrogavage. YG at different doses was administered
      to rabbits of the 3 YG groups by gastrogavage. The intervention lasted for 4
      weeks, once per day. After treatment the urine volume and pathomorphological
      changes of renal medulla tissue were observed. mRNA and its protein expression
      levels of AQP2 were detected. RESULTS: Compared with the normal control group,
      the urine volume decreased significantly, mRNA and protein expression levels of
      renal medulla AQP2 increased significantly in the model group (all P < 0.01).
      Compared with the model group, the urine volume increased significantly, and mRNA
      and protein expression levels of renal medulla AQP2 decreased significantly in
      all medicated groups (all P < 0.01). Compared with the low dose YG group, the
      urine volume significantly increased and the mRNA expression level of renal
      medulla AQP2 significantly decreased in the middle and high dose YG groups (all P
      < 0.01). The expression level of AQP2 protein significantly decreased in the high
      dose YG group (P < 0.01). Pathological changes of the renal medulla was the most
      obviously seen in the model group. But they were alleviated to various degrees in
      all medicated groups. They were more obviously attenuated in the middle and high
      dose YG groups. CONCLUSION: YG could improve CHF possibly through down-regulating
      mRNA and protein expression levels of AQP2 in renal medulla, and elevating the
      urine volume.

PMID- 25951642
TI  - [Epimedin C induced mesenchymal stem cells C3H/10T1/2 to differentiate into
      endothelioid cells in vitro: an experimental study].
AB  - OBJECTIVE: To study the endothelioid differentiation effect of Epimedin C on
      murine embryonic mesenchymal stem cells (C3H/10T1/2). METHODS: C3H/10T1/2 cells
      were cultivated in vitro. The cytotoxicity of Epimedin C at different
      concentrations was determined by MTT assay and crystal violet assay.
      Morphological changes were observed under microscope after treated with Epimendin
      C. The effect of Epimendin C on the cell cycle distribution was determined by
      flow cytometry. mRNA expression levels of endothelial markers, such as CD31,
      CD34, vascular endothelial zinc finger 1 (Vezf1), angiopoietin 1 (Ang1), and
      angiopoietin 2 (Ang2) were detected by semi-quantitative PCR. Protein expression
      levels of platelet endothelial adhesive molecule 1 (CD31), ecto-5'-nucleotidase
      (CD73), endothelial cell specific molecule-1 (ESM-1), and integrin beta5 were
      determined by immunocytochemical (IHC) staining. RESULTS: Epimedin C could not
      affect the survival rate of C3H/10T1/2 cells at 1-30 MUmol/L. Its cell cycle
      distribution was not significantly changed after treated by 30 MUmol/L Epimedin C
      for 24 h. C3H/10T1/2 cells were differentiated to vascular endothelial cells by
      Epimedin C treatment, with significant morphological changes (whirlpool-like
      structure). PCR results indicated that mRNA levels of classic endothelial mark-
      ers, namely CD34, Vezf1, Ang1, and Ang2 were significantly increased in
      C3H/10T1/2 cells after treated with Epimedin C for 5 days (P < 0.05, P < 0.01).
      Protein expression levels of CD31, CD73, and ESM-1 were also positively expressed
      after treated with Epimedin C for 5 days, showing statistical difference when
      compared with those of the control group (P < 0.01, P < 0.05). CONCLUSION:
      Epimendin C could induce C3H/10T1/2 cells to differentiate into endothelioid
      cells.

PMID- 25951641
TI  - [Effect of electro-acupuncture at Neiguan (PC6) and Lieque (LU7) on the
      expression of protein kinases in cardiomyocytes of myocardial ischemia rats].
AB  - OBJECTIVE: To study the effect of electro-acupuncture (EA) at Neiguan (PC6) and
      Lieque (LU7) on the expression of protein kinases in cardiomyocytes of myocardial
      ischemia (MI) rats. METHODS: Healthy male SD rats were randomly divided into the
      control group, the model group, the Neiguan point group, the Lieque point group,
      and the non-meridian non-acupoint group, 10 in each group by random digit table.
      The MI rat model was established by injecting isoprenaline hydrochloride (85
      mg/kg). EA at Neiguan (PC6), Lieque (LU7), and non-meridian non-acupoint were
      respectively performed. Changes of the expression of protein kinases [such as
      protein kinase A (PKA), protein kinase C (PKC), protein kinase G (PKG)] in rat
      cardiomyocytes were observed using Western blot. RESULTS: Compared with the
      control group, expression levels of PKA, PKC, and PKG increased obviously in the
      model group (P < 0.01). Compared with the model group, expression levels of PKA,
      PKC, and PKG decreased in the Neiguan point group and the Lieque point group (P <
      0.01, P < 0.05). Expression levels of PKA decreased in the non-meridian non
      acupoint group (P < 0.01). Compared with the Neiguan point group, expression
      levels of PKA, PKC, and PKG increased in the non-meridian non-acupoint group and
      the Lieque point group (P < 0.01, P < 0.05). Compared with the Lieque point
      group, expression levels of PKA, PKC, and PKG increased in the non-meridian non
      acupoint group (P < 0.01, P < 0.05). CONCLUSION: EA at Neiguan (PC6) and Lieque
      (LU7) could decrease protein expression levels of PKA, PKC and PKG in rat
      myocardial cells, and the effect of acupuncture at Neiguan (PC6) was better than
      that obtained by EA at Lieque (LU7).

PMID- 25951643
TI  - [Wnt/beta-catenin signal pathway mediated Salidroside induced directional
      differentiation from mouse mesenchymal stem cells to nerve cells].
AB  - OBJECTIVE: To explore the molecule mechanism of Salidroside inducing directional
      differentiation of mouse mesenchymal stem cells (MSCs) into neuronal cells.
      METHODS: The mouse multipotent mesenchymal precursor cell line (D1) was taken as
      the objective. Cultured MSCs were divided into the negative control group
      (complete culture solution), the positive control group (containing 1 mmol/L beta
      mercaptoethanol), the Salidroside induced group (20 mg/L Salidroside), and the
      blocked group (20 ng/ ml DKK1, a special inhibitor of Wnt/beta-catenin signal
      pathway). All cells were inoculated in a 6-well plate (1 x 10(4) cells/cm2) and
      grouped for 24 h. The expression of p-catenin was detected by fluorescence
      Immunochemistry in the negative control group, the positive control group, and
      the Salidroside induced group. The expression of neuron-specific enolase (NSE),
      beta 3 class III tubulin (beta-tubulin III), nuclear receptor related factor 1
      (Nurr1), glial fibrillary acidic protein (GFAP) mRNA, Wnt3a, beta-catenin, low
      density lipoprotein receptor-related protein6 (LRP6), Axin mRNA were detected
      using reverse transcrip- tion PCR (RT-PCR). The expression of beta-catenin and
      NSE protein were analyzed by Western blot in the negative control group, the
      positive control group, and the Salidroside induced group. Ca2+ chelating agents
      (EGTA), L-type Ca2+ channel blocker (Nifedpine), and IP3Ks special inhibitor
      (LY294002) were used to block Ca2+ signal pathway respectively. The expression of
      Wnt3a, LRP-6, Axin, glycogen syn- thase kinase (GSK-3), and beta-catenin mRNA
      were detected by RT-PCR. The beta-catenin protein expression was analyzed using
      Western blot. RESULTS: Compared with the positive control group, beta-catenin
      protein was strong positively expressed; the expression of Wnt3a, beta-catenin,
      LRP6, Axin, NSE, beta-tubulin III, Nurr1 mRNA, and NSE protein were obviously up
      regulated in the Salidroside induced group (P < 0.01). Compared with the positive
      control group and the Salidroside induced group, beta-catenin, NSE, Nurr1, and
      beta-tubulin III mRNA expression decreased; beta-catenin and NSE protein
      expression were also down-regulated in the blocked group (P < 0.01). Compared
      with the Salidroside induced group, the expression of Wnt3a, LRP-6, beta-catenin,
      and Axin mRNA were down-regulated in the Ca2+ signal blocked group and the
      salidroside induced group (P < 0.01, P < 0.05). CONCLUSION: Salidroside affected
      directional differentia- tion of MSCs into neuronal cells through Wnt/beta
      catenin and Ca2+ signal pathway.

PMID- 25951645
TI  - [Treatment of hypertension by acupuncture method of "activating blood and
      dispersing wind, harmonizing Gan-Pi": an analysis of its principle of the
      circular motion of ancient Chinese medicine].
AB  - Hypertension is one of main risk factors for the occurrence and death of stroke
      and coronary heart disease. Its prevalence rate is rising year by year. It
      severely threatens the health of the human beings. The acupuncture method of
      "activating blood and dispersing wind, harmonizing Gan-Pi" for treating
      hypertension launched by Academician SHI Xue-min has aroused great attention due
      to good cur- ative effect and less adverse reactions. In this paper principles of
      the circular motion covered by the acupuncture method of "activating blood and
      dispersing wind, harmonizing Gan-Pi" were clarified.

PMID- 25951644
TI  - [Effect of Bushen Gujin Recipe on serum and synovia interleukin-1 and tumor
      necrosis factor-alpha of knee osteoarthritis model rabbits].
AB  - OBJECTIVE: To explore the effect of Bushen Gujin Recipe (BGR) on serum and
      synovial expression of interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF
      alpha) in knee osteoarthritis (KOA) model rabbits. METHODS: Totally 36 8-month
      old healthy male New Zealand white rabbits were randomly divided into 4 groups,
      i.e., the normal control group, the model group, the Western medicine group
      (Meloxicam, at the daily dose of 6 mg/kg), and the TCM group (BGR, at the daily
      dose of 53 g/kg), 9 in each group. Modeling was performed in all rabbits except
      those in the normal control group by using Hulth A method. All medication was
      performed for 8 consecutive weeks. Contents of IL-1 and TNF-alpha were detected
      using ELISA from serum, partial synovial tissue of the front knee joint,
      cartilage and subchondral bone of the medial femoral condyle. RESULTS: The joint
      space became narrowed in the Western medicine group, ranging between the model
      group and the TCM group. The articular surface was rough with obvious
      osteophytes. The joint space was slightly narrower in the TCM group; the
      articular surface was slightly rough with mild osteophytes. Compared with the
      normal control group, contents of IL-1 and TNF-alpha in serum and synovial
      increased in the model group (P < 0.01). Compared with the model group, contents
      of IL-1 and TNF-alpha in serum and the synovial fluid decreased in the two
      treatment groups (P < 0.01). There was no statistical difference in contents of
      IL-1 and TNF-alpha between the Western medicine group and the TCM group.
      CONCLUSION: BGR promoted the synthesis of cartilage matrix and carti- lage repair
      through inhibiting the secretion of IL-1 and TNF-alpha, and prolonging cartilage
      degeneration.

PMID- 25951646
TI  - [Promoting discipline development by the discipline evaluation--based on data
      analysis of integrative medicine at Beijing University of Chinese Medicine].

PMID- 25951647
TI  - [Treating breast cancer caused general anxiety disorder by strengthening vital qi
      and soothing gan method: a case report of one patient].

PMID- 25951648
TI  - [Advance in acupuncture treatment of polycystic ovarian syndrome].

PMID- 25951649
TI  - Outlook for the ACA in 2015 could be death by 1,000 cuts.

PMID- 25951650
TI  - Don't overlook importance of pharm benefits in CDHPs.

PMID- 25951651
TI  - Therapy for Parkinson's psychosis closer to market.

PMID- 25951652
TI  - Chronic care management payments: another step away from fee-for-service.

PMID- 25951653
TI  - 2 hot issues facing the medical device industry in 2015: registries and taxes.

PMID- 25951654
TI  - New hope for newborns with rare deforming disease.

PMID- 25951655
TI  - Providers warming up to mobile health devices.

PMID- 25951656
TI  - Economic impact of a novel naloxone autoinjector on third-party payers.
AB  - BACKGROUND: Patient overdoses on prescription opioid analgesics in the United
      States continue to rise, resulting in increased emergency department and
      hospitalization costs. Opioid overdose is readily reversible with naloxone, a
      fast-acting opioid antagonist. A new naloxone autoinjector (NAI), Evzio, which
      does not require medical training to use, was approved by the FDA in April 2014.
      Payers must decide on reimbursement policies for this product. PURPOSE: To
      demonstrate to payer decision makers the costs and potential medical resource
      cost offsets associated with the utilization of a new NAI. DESIGN: A
      deterministic model using matched controls. METHODOLOGY: An Excel-based cost
      model was developed for a hypothetical health plan with 1 million adult members.
      Costs of prescription opioid overdose events for patients appropriately dispensed
      NAI were compared with matched controls. RESULTS: NAI prescriptions increased
      from 218 in Year 1 to 2,527 in Year 3. In Year 3, 86 NAI patients (and their
      matched controls) experienced opioid overdose events. For this period, fatal
      overdoses in the NAI cohort totaled 11.1 vs. 14.7 for the control group. In Year
      3, 2.5 deaths (10.1-7.6) were avoided. NAI acquisition costs rose from $125,000
      in Year 1 (PMPM = $0.01) to nearly $1.5 million in Year 3 (PMPM = $0.12).This
      cost was offset by medical resource savings of approximately $84,000 in Year 1,
      increasing to $975,000 in Year 3. The total net cost (NAI less offsets) in Year
      3, when NAI uptake was assumed to plateau, was $481,000 (PMPM = $0.04).
      CONCLUSION: A deterministic model demonstrated that NAI acquisition costs can be
      offset through medical cost reductions with improved timely access to naloxone.

PMID- 25951657
TI  - Feds adjust Medicare spending growth projections downward.

PMID- 25951658
TI  - Design, synthesis and evaluation of biological activity of novel fasudil
      analogues.
AB  - Nine isoquinoline Rho kinase inhibitors were designed and synthesized on the
      basis of a ligand-binding pocket model. With fasudil, the only Rho kinase
      inhibitor marketed to date, as a reference compound, their biological activities
      were determined, including assays of Rho kinase inhibitory activity, synapse
      formation, cell viability. Bio-assays were performed by means of MTT 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assays and lactate
      dehydrogenase (LDH) assays. The obtained results indicated that (R)-6H-1-(5
      isoquinolinesulfonyl)-2-hydroxy methyl-1-pyrrolidine and (R)-6H-1-(5
      isoquinolinesulfonyl)-2-chloromethyl-1-pyrrolidine exhibited excellent Rho kinase
      inhibitory activity, deactivation of Rho kinase led to accelerated synapse
      formation and enhanced cell viability. Therefore they might be potential
      candidates for preventing various neurological disorders. The brief study on the
      structure-activity relationship of these isoquinoline analogues demonstrated that
      modification of inhibitors targeting region D of the Rho kinase binding pocket is
      quite efficacious, the existence of free amino, chloro- or hydroxyl group as
      binding sites with region D of Rho kinase is necessary for increasing the
      inhibitory activity.

PMID- 25951659
TI  - Dissolution enhancement of gliclazide using ultrasound waves and stabilizers in
      liquid anti-solvent precipitation.
AB  - The absorption rate of gliclazide is slow and variable among subjects probably
      due to poor dissolution from the dosage form. The objective of this study was to
      enhance the dissolution rate of gliclazide by reducing the particle size.
      Gliclazide was precipitated from an acetone solution by adding an antisolvent
      (water) containing stabilizers. A combination of jets (flow rate of 20 ml/min),
      ultrasound, HPMC 4000, and sodium dodecyl sulfate was used to control particle
      size and particle size distribution. The effects of concentration of stabilizers,
      initial drug concentration in solution, time of insonation, antisolvent-to
      solvent ratio, and ultrasound power on particle size and particle size
      distribution were studied. Precipitated drug particles were characterized by
      laser diffraction particle size analysis, SEM, FTIR spectroscopy, DSC, powder x
      ray diffraction and in-vitro dissolution. With increasing almost all the studied
      parameters, the particle size of gliclazide initially decreased, exhibited a
      minimum, and then increased. Drug particles of glicazide with a mean particle
      size of 1.56 +/- 0.09 MUm and a narrow size distribution (d10/d50/d90 =
      0.67/1.67/2.26) were precipitated as compared to unprocessed gliclazide with a
      mean particle size of 10.67 +/- 0.04 MUm and a wide size distribution
      (d10/ds50/d90 = 4.53/9.88/18.03). SEM images indicated changes in the particle
      morphology. Powder x-ray diffraction patterns and DSC curves indicated no changes
      in the chemical properties but only decrease in crystallinity and/or particle
      size. The dissolution rate was enhanced 2.55-fold. In conclusion, drug particles
      with small size and narrow size distribution were precipitated by selecting
      favorable process conditions, and dissolution was enhanced several folds.

PMID- 25951660
TI  - Absorption, disposition, metabolism, and excretion of ritobegron (KUC-7483), a
      novel selective beta3-adrenoceptor agonist, in rats.
AB  - The pharmacokinetic profile of ritobegron, a novel, selective beta3-adrenoceptor
      agonist, was investigated in rats. Ritobegron, an ethyl ester prodrug of the
      active compound KUC-7322, or KUC-7322 itself was orally administered (10 mg/kg).
      Ethyl esterification resulted in a 10-fold increase in the area under the plasma
      concentration-time curve (AUC(0-t)), as compared to KUC-7322. Following
      intravenous administration of KUC-7322 (1 mg/kg), total blood clearance was 1.36
      L/h/kg, suggesting that intrinsic hepatic clearance is the rate-limiting step in
      KUC-7322 excretion. When ritobegron was orally administered (0.3, 1, 3, and 10
      mg/kg), plasma concentrations of KUC-7322 rapidly increased and reached a maximum
      concentration (C(max)) at 0.25 to 0.31 h. KUC-7322 levels rapidly decreased, with
      a half-life (t 1/2) of 0.42 to 1.37 h thereafter. AUC(0-t) did not show a dose
      dependent increase. The bioavailability of KUC-7322 was estimated to be 4%.
      Following oral administration of [14C]ritobegron (3 mg/kg), radioactivity
      concentrations in tissues rapidly increased and declined in parallel with changes
      in plasma concentration. In most of tissues, excluding the liver, kidney, urinary
      bladder, stomach and small intestine, radioactivity concentrations were lower
      than that in plasma. In plasma, bile, urine, and feces, KUC-7322 and its
      glucuronide, sulfate, and glutathione conjugates were detected. The glucuronide
      conjugate of KUC-7322 was the predominant metabolite in bile, plasma, and urine,
      and KUC-7322 was predominant in feces. Ritobegron was not detected in any of the
      samples. The cumulative excretion of radioactivity in urine and feces were 28.7%
      and 68.3% of the dose, respectively, up to 120 h after administration.

PMID- 25951661
TI  - Effect of lithium chloride on endoplasmic reticulum stress-related PERK/ROCK
      signaling in a rat model of glaucoma.
AB  - Elevated intraocular pressure (IOP) is considered as the major risk factor for
      the loss of retinal ganglion cells (RGCs) and their axons in glaucoma. Lithium
      chloride (LiCl) inhibits glycogen synthase kinase-3 beta (GSK-3beta) and attends
      PERK-induced endoplasmic reticulum stress (ERs) transition. PERK is a type I
      transmembrane protein located in the endoplasmic reticulum. PERK pathway
      activation takes place in ERs early inhibiting protein synthnesis to protect cell
      and promote cell survival. Here, we firstly evaluate that LiCl reduced IOP when
      administered intraperitoneally. After 6 weeks, IOP dropped by around 21.9% in
      LiCl treated rats. Then we investigated the effects of LiCI on PERK-mediated
      signaling pathways. LiCl treatment activated PERK and inhibited the expression of
      ROCK-1 and ROCK-2 in a rat model of glaucoma. Collectively, these results suggest
      that LiCl reduced the IOP through the phosphorylation of PERK by the regulation
      of PERK/ROCK signaling in glaucoma rat model.

PMID- 25951662
TI  - Effect of licorice on the induction of phase II metabolizing enzymes and phase
      III transporters and its possible mechanism.
AB  - Licorice has a marked detoxifying effect that can treat drug poisoning and/or
      relieve adverse effects. However, the exact mechanism of this action is not
      entirely elucidated, but is believed to be related to the modulation of drug
      disposition when interacting with other drugs. Additionally, Nuclear factor
      erythroid 2-related factor 2 (Nrf2) plays a significant role in mediating phase
      II xenobiotic metabolizing enzymes (XMEs) and phase III transporters. In the
      present study, we showed that licorice induced the mRNA expression of phase II
      XMEs UDP-glucuronosyltransferases 1A1 (UGT1A1), glutamate cysteine ligase (GCL),
      glutathione-s-transferase (GST) and phase III transporters multidrug resistance
      protein 2 (MRP2), as well as a rapid increase in Nrf2 nuclear accumulation. These
      findings suggests that licorice may intervene in the Nrf2 signal pathway to
      induce UGT1A1, GCLC, GST and MRP2, which provide a novel mechanism for the use of
      licorice to treat drug poisoning and/or relieve adverse effects.

PMID- 25951663
TI  - The role of CYP2C9 genetic polymorphisms in the oxidative metabolism of
      diclofenac in vitro.
AB  - CYP2C9 is one of four known members of the human cytochrome P450 CYP2C
      superfamily, with at least 57 CYP2C9 alleles being previously identified. Genetic
      polymorphisms of CYP2C9 significantly influence the efficacy and safety of some
      drugs, which might cause adverse effects and therapeutic failure. The purpose of
      the present study was to clarify the role of 36 CYP2C9 alleles, 21 novel alleles
      (*36-*56) found in the Chinese population, in the oxidative metabolism of
      diclofenac in vitro. Insect microsomes expressing the 36 human CYP2C9 alleles
      were incubated with 2-100 MUM diclofenac for 30 min at 37 degrees C and
      terminated by the addition of 30 MUL 0.1 M HCl. Diclofenac and 4'-hydroxyl (OH)
      diclofenac, the major diclofenac metabolite, were analyzed by high-performance
      liquid chromatography (HPLC). Compared with wild-type CYP2C9*1, most variants
      showed significantly altered values in V(max), K(m) and intrinsic clearance
      (V(max)/K(m)). Only one variant exhibited markedly increased intrinsic clearance
      value, whereas 31 variants exhibited significantly decreased values. Thus, this
      study demonstrated that more attention should be given to subjects carrying these
      CYP2C9 alleles when administering diclofena.

PMID- 25951664
TI  - Protective effect of metformin on renal injury of C57BL/6J mouse treated with
      high fat diet.
AB  - This study aimed to investigate the protective effect of metformin on renal
      injury of C57BL/6J mice treated with a high fat diet. High-fat diet for 12 weeks
      was used to establish the mice model of metabolism syndrome and the intervention
      of metformin (75 mg x kg(-1) x d(-1)) for 4 weeks, and plasma biochemical
      indicator and body weight were used to evaluate the model. Sterol regulatory
      element-binding protein (SERBP)-1c, TNF-alpha, NADPH Oxidase (NOX)4 mRNA was
      determined by real time-PCR. Phospho-AMP-activated protein kinase (P-AMPK)alpha
      protein was detected by western blotting. Oil Red O staining, Masson staining and
      HE staining were for observing renal pathological changes. At the end of 12th
      week, compared with mice on low fat diet (LFD), body weight (BW), the levels of
      fasting insulin (FINS), plasma and renal triglyceride (TG) were higher and plasma
      high density lipoprotein (HDL) and insulin sensitivity index (ISI) were
      significantly lower, but the levels of fasting blood glycemia (FBG), plasma total
      cholesterol (TC) and renal TC had no changes; Oil Red O staining revealed renal
      lipids deposition, Masson staining and HE staining revealed glomerular
      hypertrophy, matrix increasing, and inflammatory cells infiltration in
      glomerular; the expression of p-AMPKalpha protein decreased and the expression of
      SREBP-1c, TNF-alpha, NOX4 mRNA increased significantly in mouse treated with high
      fat diet (HFD). Compared with the HFD group, through metformin interventing,
      metabolic disorders were significantly improved, renal lipids deposition and
      other pathological changes were ameliorated, the expression of p-AMPKalpha
      protein increased and the expression of SREBP-1c, TNF-alpha, NOX4 mRNA decreased
      significantly. Metformin improved metabolic disorders, upregulated activity of
      renal AMPK, diminished the expression of renal SREBP-1c, TNF-alpha, NOX4 mRNA,
      decreased accumulation of renal lipids, and prevened renal injury.

PMID- 25951666
TI  - Cytotoxic activities of hydroxyethyl piperazine-based sigma receptor ligands on
      cancer cells alone and in combination with melphalan, PB28 and haloperidol.
AB  - sigma Receptor ligands are attracting interest as possible anti-cancer agents
      because of their ability to induce cell death by different mechanisms. In this
      study we investigated the cytotoxic effects of 12 recently developed sigma
      receptor ligands in a panel of eight different human tumor cell lines by either
      the crystal violet or MTT assays. The results show that sigma ligands have broad
      cytotoxic activity on a number of human cancer cell lines with IC50 values in the
      low MUM range. In addition, apoptosis was observed by the annexin-V/PI double
      staining method when RPMI 8226 human multiple myeloma cells were treated with a
      representative sigma ligand, (R)-2b. Combination of (R)-2b with melphalan led to
      a higher apoptotic rate than with the drug alone. Likewise, combined treatment of
      (R)-2b with the known high affinity sigma2-agonist PB28 showed an additive effect
      on the induction of apoptosis in the RPMI 8226 line. In contrast, combinations of
      (R)-2b with the known sigma1-antagonist haloperidol lead to a significant
      reduction in the cytotoxic activity of (R)-2b. These results support the idea
      that (R)-2b acts as a sigma-agonist to cause the death of RPMI 8226 cells.

PMID- 25951665
TI  - Venlafaxine inhibits apoptosis of hippocampal neurons by up-regulating brain
      derived neurotrophic factor in a rat depression model.
AB  - The effect of venlafaxine on the expression of brain-derived neurotrophic factor
      (BDNF) in rat hippocampal neurons was studied, as well as its inhibitory effect
      on apoptosis of hippocampal neurons. Differences in behavioral ability between
      the depression model group and the venlafaxine treatment group were observed in
      behavioral, sucrose-water and open field tests. The rat hippocampal tissue was
      sliced, stained and observed for BDNF distribution by immunohistochemistry.
      Apoptosis of hippocampal neurons was detected by TUNEL. BDNF expression in the
      hippocampal tissue was detected by Western blot. Injury and apoptosis of the
      hippocampal tissue were observed by electron microscopy. Behavioral test showed
      that venlafaxine effectively improved the behavioral abilities of depressed rats.
      Immunohistochemistry showed that venlafaxine markedly increased BDNF expression
      in the rat hippocampus. TUNEL showed that venlafaxine markedly inhibited
      apoptosis of hippocampal neurons, which was also confirmed by electron
      microscopic observation of the pathologic sections. Venlafaxine improved the
      expression of BDNF by influencing the PI3k/PKB/eNOS pathway and repressed the
      apoptosis of hippocampal neurons.

PMID- 25951667
TI  - The redox status of human breast cancer cell lines (MCF-7 and MDA-MB231) treated
      with novel dinuclear berenil-platinum(II) complexes.
AB  - This study compared the effects of cisplatinum and novel berenil-platinum(ll)
      complexes on the redox status of breast cancer cells that were estrogen receptor
      positive (MCF-7) or estrogen receptor-negative (MDA-MB231). Both cell lines were
      treated with cisplatinum or the following berenil-platinum(ll) complexes:
      Pt2(isopropylamine)4(berenil)2, Pt2(piperidine)4(berenil)2, Pt2(2
      picoline)4(berenil)2, Pt2(3-picoline)4(berenil)2, and Pt2(4-picoline)4(berenil)2.
      Changes in levels of reactive oxygen species, levels and activities of
      antioxidants, and lipid peroxidation products levels were measured. All
      investigated compounds enhanced ROS generation, reduced the activity of
      antioxidant enzymes (e.g., glutathione peroxidase and glutathione reductase), and
      decreased levels of small-molecule antioxidants (GSH, vitamins E and A). Such
      conditions are conducive to generating oxidative stress and phospholipids
      peroxidation. Cellular phospholipids in MCF-7 cells were most sensitive to the
      Pt2(isopropylamine)4(berenil)2 complex, whereas MDA-MB231 cells were not
      particularly sensitive to any berenil-platinum(ll) complex. These findings will
      facilitate future anticancer drug design strategy for breast cancer
      pharmacotherapy.

PMID- 25951668
TI  - Facial fractures in children: a historical perspective on treatment techniques.
AB  - The surgical principles for the treatment of facial fractures in children have
      evolved progressively over the past 70 years. In 1943 Waldron and colleagues
      published what is probably the first paper on the subject, thus setting a
      paradigm for the conservative treatment of pediatric facial fractures. This
      standard remained viable for about five decades. Therefore, during many years
      children with facial fractures did not benefit in the same manner as their adult
      counterparts from the multiple advances made in the management of facial trauma.
      In the 1990s craniofacial surgeons used plates and screws to correct craniofacial
      deformities in children with congenital malformations. As a consequence of their
      findings, pediatric oral and maxillofacial surgeons started to apply such
      principles to the management of facial fractures in young, growing patients,
      which eventually paved the way for the open reduction with external fixation
      paradigm. The aims of this article are to detail Waldron's initial directives, to
      evaluate the publications that contributed to its consolidation, and to analyze
      the factors that led to its challenge fifty years later.

PMID- 25951669
TI  - Historical Perspectives III. The DG 16 explorer.

PMID- 25951670
TI  - Drs. Smith Brothers: dental surgeons of Calcutta.
AB  - During the British raj, India attracted dental practitioners from all over the
      world who set up practices in the Presidency towns of Calcutta, Bombay, Madras
      and Bangalore. Lured by the abundant opportunity to make good money, these
      mercenary but courageous dentists counted Viceroys, Indian royalty and political
      leaders amongst their clients. Some, like the famous American Smith Brothers of
      Calcutta, were sought after even by the rulers of neighboring countries. Dr. Mark
      Smith's hazardous visit to the Amir of Afghanistan made worldwide headlines more
      than 100 years ago for the fabulous fee he was paid for the dental treatment.
      This paper briefly describes the exploits and experiences of the Smith brothers
      while in India.

PMID- 25951671
TI  - A century-old "flipper".

PMID- 25951672
TI  - Johann Baptist Spix and the "lingula mandibularis".
AB  - Johann Baptist Ritter von Spix (1781-1826), a German zoologist, was famous in his
      time and highly honored after making one of the first exploration voyages in the
      wildest part of Brazil. He was almost forgotten in the annals of history for
      nearly two centuries after his birth, at which time some enlightened biographers
      brought him back into prominence in both the biological and zoological fields. On
      the contrary though, he had never been forgotten in the science of
      odontostomatology thanks to his discovery of the "Lingula Mandibularis" also
      known as "Spine of Spix". Johannes Baptist Spix was born in Hoechstadt, Germany
      in 1781. He was the Conservator of the Museum of Natural History in Munich and
      was a distinguished Comparative Anatomist. He died Munich inl 1826. The purposes
      of this work are to present some biographical notes on J.B. Ritter von Spix, to
      explain whythe "Lingula Mandibularis" has been called by the name of Spix and why
      this eponym has been used as such.

PMID- 25951673
TI  - Longing for modern composite materials in the late 1800s.
AB  - Restoring teeth in the late 1800s required ingenuity and creativity, as the
      materials available were a far cry from is presently used. Likewise, restorative
      preparation designs had not yet been promulgated by GV Black. Concerns about both
      restorations that contracted due to the nature of the filling material and
      retention of sound tooth structure in favor of cutting away dentin and enamel in
      order to place "metal caps" were held by many dentists. While some dental
      professionals had a vision for the ideal restorative materials, they made do with
      what they had in an attempt to provide quality dentistry.

PMID- 25951675
TI  - Dental postcard LVII. Don't chew the rag!

PMID- 25951674
TI  - Dental trade cards XLII. Dr. John Parain.

PMID- 25951676
TI  - Darwin on dentistry.

PMID- 25951677
TI  - The Belmont Report. Ethical principles and guidelines for the protection of human
      subjects of research.
AB  - On July 12, 1974, the National Research Act (Pub. L. 93-348) was signed into law,
      thereby creating the National Commission for the Protection of Human Subjects of
      Biomedical and Behavioral Research. One of the charges to the Commission was to
      identify the basic ethical principles that should underlie the conduct of
      biomedical and behavioral research involving human subjects and to develop
      guidelines which should be followed to assure that such research is conducted in
      accordance with those principles. In carrying out the above, the Commission was
      directed to consider: (a) the boundaries between biomedical and behavioral
      research and the accepted and routine practice of medicine, (b) the role of
      assessment of risk-benefit criteria in the determination of the appropriateness
      of research involving human subjects, (c) appropriate guidelines for the
      selection of human subjects for participation in such research and (d) the nature
      and definition of informed consent in various research settings. The Belmont
      Report attempts to summarize the basic ethical principles identified by the
      Commission in the course of its deliberations. It is the outgrowth of an
      intensive four-day period of discussions that were held in February 1976 at the
      Smithsonian Institution's Belmont Conference Center supplemented by the monthly
      deliberations of the Commission that were held over a period of nearly four
      years. It is a statement of basic ethical principles and guidelines that should
      assist in resolving the ethical problems that surround the conduct of research
      with human subjects. By publishing the Report in the Federal Register, and
      providing reprints upon request, the Secretary intends that it may be made
      readily available to scientists, members of Institutional Review Boards, and
      Federal employees. The two-volume Appendix, containing the lengthy reports of
      experts and specialists who assisted the Commission in fulfilling this part of
      its charge, is available as DHEW Publication No. (OS) 78-0013 and No. (OS) 78
      0014, for sale by the Superintendent of Documents, U.S. Government Printing
      Office, Washington, DC 20402. Unlike most other reports of the Commission, the
      Belmont Report does not make specific recommendations for administrative action
      by the Secretary of Health, Education, and Welfare. Rather, the Commission
      recommended that the Belmont Report be adopted in its entirety, as a statement of
      the Department's policy. The Department requests public comment on this
      recommendation.

PMID- 25951678
TI  - World Medical Association Declaration of Helsinki: ethical principles for medical
      research involving human subjects.
AB  - Published research in English-language journals are increasingly required to
      carry a statement that the study has been approved and monitored by an
      Institutional Review Board in conformance with 45 CFR 46 standards if the study
      was conducted in the United States. Alternative language attesting conformity
      with the Helsinki Declaration is often included when the research was conducted
      in Europe or elsewhere. The Helsinki Declaration was created by the World Medical
      Association in 1964 (ten years before the Belmont Report) and has been amended
      several times. The Helsinki Declaration differs from its American version in
      several respects, the most significant of which is that it was developed by and
      for physicians. The term "patient" appears in many places where we would expect
      to see "subject." It is stated in several places that physicians must either
      conduct or have supervisory control of the research. The dual role of the
      physician-researcher is acknowledged, but it is made clear that the role of
      healer takes precedence over that of scientist. In the United States, the federal
      government developed and enforces regulations on researcher; in the rest of the
      world, the profession, or a significant part of it, took the initiative in
      defining and promoting good research practice, and governments in many countries
      have worked to harmonize their standards along these lines. The Helsinki
      Declaration is based less on key philosophical principles and more on
      prescriptive statements. Although there is significant overlap between the
      Belmont and the Helsinki guidelines, the latter extends much further into
      research design and publication. Elements in a research protocol, use of
      placebos, and obligation to enroll trials in public registries (to ensure that
      negative findings are not buried), and requirements to share findings with the
      research and professional communities are included in the Helsinki Declaration.
      As a practical matter, these are often part of the work of American IRBs, but not
      always as a formal requirement. Reflecting the socialist nature of many European
      counties, there is a requirement that provision be made for patients to be made
      whole regardless of the outcomes of the trial or if they happened to have been
      randomized to a control group that did not enjoy the benefits of a successful
      experimental intervention.

PMID- 25951679
TI  - Code of ethics for dental researchers.
AB  - The International Association for Dental Research, in 2009, adopted a code of
      ethics. The code applies to members of the association and is enforceable by
      sanction, with the stated requirement that members are expected to inform the
      association in cases where they believe misconduct has occurred. The IADR code
      goes beyond the Belmont and Helsinki statements by virtue of covering animal
      research. It also addresses issues of sponsorship of research and conflicts of
      interest, international collaborative research, duty of researchers to be
      informed about applicable norms, standards of publication (including plagiarism),
      and the obligation of "whistleblowing" for the sake of maintaining the integrity
      of the dental research enterprise as a whole. The code is organized, like the ADA
      code, into two sections. The IADR principles are stated, but not defined, and
      number 12, instead of the ADA's five. The second section consists of "best
      practices," which are specific statements of expected or interdicted activities.
      The short list of definitions is useful.

PMID- 25951680
TI  - Uniform requirements for manuscripts submitted to biomedical journals (excerpts).
AB  - The Vancouver Convention is renowned among editors who publish dental and related
      research. It is the standard for what content goes in the Methods section, how
      tables and figures are to be laid out, and how references are to be cited, among
      many other particulars. Almost no biomedical research journals follow the
      Vancouver Convention in every detail; virtually all come very close. In addition
      to the mechanics of manuscript submission and formatting for publication, the
      Vancouver Convention is looked to as the standard for the ethics of publication.
      Common practice is defined for who counts as an author to what constitutes an
      acceptable republication. Very clear language is included regarding conformity
      with the Belmont Report or Helsinki Declaration and other requriments for ethical
      treatment of subjects. Conflicts of interest, confusion of advertising with
      research, relations with the popular press, and sponsorship of supplements are
      addressed. The Vancouver Convention makes a special point of emphasizing the
      responsibility of journal editors as having the final check in the chain of
      research ethics that begins with scientists pursuing a line of inquiry and ends
      when the results are reported. The Journal of the American College of Dentists
      endorses and honors the Vancouver Convention. In 2000, the Board of Regents of
      the American College of Dentists and the officers of the American Association of
      Dental Editors approved a joint Code of Ethics for Dental Editors. The code is
      based on the Vancouver Convention, but also addresses journal content beyond
      reports of research findings. The joint ACD-AADE code can be accessed at
      http://acd.org/ codefordentaleditors.htm.

PMID- 25951681
TI  - The ethics of experimenting in dental practice.
AB  - There is a common misconception that scientists conduct research in their labs or
      clinics and practitioners do not experiment, but only use the best results
      reported in the literature. This confusion comes about because dentists are not
      trained in, nor do they normally observe, the formal requriments of research
      protocol or ethics. It is generally believed that the norms that apply to
      clinical practice also cover all situations where dentists innovate in their
      treatment protocols with a view toward discovering more effective ways to treat
      patients or where they modify a standard protocol in hopes of better serving the
      needs of an atypical patient. In this 2002 paper from the Dental Clinics of North
      America (Volume 46, Number 1, pp. 29-44), David W. Chambers challenges the
      concept that useful general knowledge is created only outside dental practice and
      then transferred into the office. But if it is the case that practitioners
      experiment, even to the limited extent of customizing materials and methods to
      their own needs or the particular circumstances of patients, there are ethical
      considerations. All modifications are not equally justifiable, the patient should
      be involved in "partially tested" approaches in a different way from the routine,
      and there needs to be sound reason to believe the innovation will not fall below
      the standard of care. Experimental practice has the characteristics of high
      probability of success, structured observation, realistic settings, and careful
      documentation. Heroic measures can only be undertaken when available options have
      failed and with full consent of the patient. A two-part ethical test is proposed
      for experimenting in practice: (a) If the dentist believes members of the
      community (patients, colleagues, or society generally) would be offended or
      outraged by an action, provided that they became aware of the relevant details-
      to not do it! (b) If the dentist believes members of the community would be
      concerned by an action, provided they became aware of the relevant details-
      discuss it with them. There is also an ethics of evaluating and adopting the
      research literature to one's office. Some of the requriments in this area include
      maintaining a current and critical familiarity with developments, understanding
      the difference between the internal validity of studies in the context where they
      were conducted and the likely adaptations or cautions needed when customizing the
      literature to individual practices, and knowing the proper weights to give to the
      literature and one's own clinical experience.

PMID- 25951682
TI  - Patients who make terrible therapeutic choices.
AB  - The traditional approaches to dental ethics include appeals to principles, duties
      (deontology), and consequences (utilitarianism). These approaches are often
      inadequate when faced with the case of a patient who refuses reasonable treatment
      and does not share the same ethical framework the dentist is using. An approach
      based on virtue ethics may be helpful in this and other cases. Virtue ethics is a
      tradition going back to Plato and Aristotle. It depends on forming a holistic
      character supporting general appropriate behavior. By correctly diagnosing the
      real issues at stake in a patient's inappropriate oral health choices and working
      to build effective habits, dentists can sometimes respond to ethical challenges
      that remain intractable given rule-based methods.

PMID- 25951683
TI  - Dental pain in the ED: costs that hurt patients and EDs.
AB  - BACKGROUND AND OBJECTIVES: The objective of this retrospective study was to
      determine if the collection rates for dental related visits to the emergency
      department (ED) are less than collection rates for ED visits for other problems.
      METHODS: Data were analyzed from one Kentucky hospital's electronic health record
      system from April 2010 to April 2012. Collection rates for patients who received
      care in the ED for uncomplicated dental problems were compared to collection
      rates for all patients who received care in the ED for any reason. RESULTS: Each
      month during the study period, an average of 77 patients presented to the ED for
      dental problems. Compensation rates for physician fees were 9.8% for dental
      related care and 39% for all patients who received care for any reason.
      Compensation rates for hospital fees were 16% for dental related care and 20.1%
      for all patients who received care for any reason. Uninsured patients accounted
      for 68.8% of physician fees and 62.4% of hospital fees for dental related care.
      CONCLUSIONS: Using the ED as a dental safety net is costly to the patient because
      the underlying problem is typically not resolved and costly to the hospital
      because of very low collection rates. In addition, other patients who present to
      the ED for non-dental, high acuity problems may have delayed care or no care
      because of the number of patients using the ED for dental pain.

PMID- 25951684
TI  - Ebola surgical protocols enhance safety of patients and personnel.

PMID- 25951685
TI  - Best business practices shared during annual conference.

PMID- 25951686
TI  - Rich Bluni will kick off OR Manager Conference with new spin on 'engagement'.

PMID- 25951688
TI  - Gains are worth the pain in forming comanagement agreements.

PMID- 25951687
TI  - Perioperative surgical home optimizes patient care, Part 2.

PMID- 25951689
TI  - Streamline selection and stocking to make supplies available and affordable.

PMID- 25951690
TI  - Economic pressures lead ASCs to seek new owners.

PMID- 25951691
TI  - Oral hygiene in population of southern Poland.
AB  - AIMS: Proper oral hygiene is an important element in the prevention of many
      diseases. Oral hygiene habits different depending on the place of residence, age
      and public awareness. The aim of the study was assessment of oral hygiene habits
      in a group of patients admitted for cardiac surgery. MATERIAL AND METHODS: The
      database has been made on the basis of anonymous questionnaires filled by all
      participants. The study included 643 patients admitted to the hospital for
      surgical treatment of acquired heart disease. We divided patients into 3 groups
      depending on age, place of residence and type of heart disease. RESULTS: More
      than 30% of patients brush their teeth once a day or less. Over 40% of all
      respondents do not attend for regular visits to the dentist. Most patients, who
      do not brush teeth or dentures were in group > 70 years old (6%) and live in the
      countryside. Patients in a big city perform control visit the most often (64%)
      and this group had the largest proportion of pa- tients who declared that the
      visits take place once a year or more (46%). CONCLUSIONS: Habits of proper oral
      hygiene among patients scheduled for cardiac surgery are at high level. 9 out of
      10 patients declares daily teeth brushing. Among patients living in the country,
      46% do not use regular visits and only 29% go to the dentist once a year or more
      often. Education campaigns about influence of the improper oral cavity hygiene
      should be initiated.

PMID- 25951692
TI  - Lower doses of rituximab in remission induction for refractory granulomatosis
      with polyangiitis.
AB  - INTRODUCTION: Recently, rituximab (RTX)--monoclonal antibody against the CD20
      molecule on the surface of B-lymphocytes is used in the treatment of
      antineutrophil cytoplasmic antibody (ANCA) associated vasculitides. Efficacy of
      the drug administered in so-called lymphoma treatment protocol (4 x 375
      mg/m2/week) has been shown not to be inferior to cyclophosphamide. However, some
      data published lately suggest that rituximab could also be effective in much
      lower doses, which could lead to reducing side effects, but above all, the cost
      of the therapy. OBJECTIVES: Analysis of efficacy of lower doses of rituximab in
      remission induction in GPA patients. PATIENTS AND METHODS: We retrospectively
      analyzed the course, the efficacy and safety of rituximab administered at a dose
      lower than average in lymphoma treatment protocol (median = 1.0 g). The drug was
      used only in patients who presented resistance to the standard treatment with
      cyclophosphamide, or in whom such treatment was impossible. Disease activity was
      evaluated using Birmingham Vasculitis Activity Score and disease remission was
      defined as score 0. RESULTS: Out of the twelve patients who received RTX
      induction doses (period 07. 2009-07.2014), remission was achieved in the eleven
      (92%). Averaged observation period was 7.5 months (median). The total B-cell
      depletion was observed in all treated with induction scheme. During further
      follow-up, disease relapse in 2 patients was observed. One patient achieved
      remission again after re use of rituximab. The second patient died in the course
      of diffuse alveolar hemorrhage. In these patients, recurrence was observed
      respectively after 42 and 56 months of follow-up. CONCLUSIONS: The efficacy of
      lower doses of rituximab for the induction of remission in refractory
      granulomatosis with polyangiitis was confirmed. Ava- ilability of the drug in the
      treatment of primary vasculitis is currently limited mainly due to economic
      issues.

PMID- 25951693
TI  - Knowledge on the subject of human physiology among Polish high school students--a
      cross-sectional study.
AB  - BACKGROUND: In most cases the only knowledge an individual will receive with
      regards to their own body and its proper functioning is during their high school
      education. The aim of this study was to evaluate high school students' knowledge
      about basic physiology. MATERIAL AND METHODS: The research was carried out in
      five, randomly chosen high schools in Krakow, Poland. Young people in the age of
      17-19 years were asked to fill in the questionnaire designed by the authors. The
      first part of the survey included personal data. The second part contained 20
      close-ended questions assessing students' knowledge about the basics of human
      physiology. Question difficulty varied from easy through average, and up to
      difficult. The maximum number of points to achieve was 20. RESULTS: One-thousand
      and eighty-three (out of 1179 invited--91.86%) Polish high school students
      (63.25% female) filled in a 20-item questionnaire constructed by the authors
      regarding basic human physiology. The mean age of the group was 17.66 +/- 0.80
      years. The mean score among the surveyed was 10.15 +/- 3.48 (range 0-20). Only
      26.04% of students achieved a grade of 60% or more, and only one person obtained
      the highest possible score. Females achieved significantly better scores than
      males (10.49 +/- 3.38 vs. 9.56 +/- 3.56; p < 0.0001). Pupils in their second year
      who were in the process of studying physiology, obtained better results than
      those in their third year who had already finished the biology course (10.70 +/-
      3.27 vs. 9.81 +/- 3.74 respectively; p < 0.0001) and those in their first year
      who did not yet study human physiology (10.70 +/- 3.27 vs. 9.63 +/- 2.74
      respectively; p = 0.003). Over 23% of students did not know that mature red blood
      cells do not have cell nuclei and a similar number of them answered that humans
      have 500,000 erythrocytes in 1 mm3 of blood. Over 32% believed that plasma does
      not participate in the transport of respiratory gases, and 31% believed that
      endocrine glands secrete hormones within their immediate vicinity and into the
      blood. CONCLUSIONS: Our research has shown that young people, especially men,
      often lack basic physiological knowledge needed to make conscious and responsible
      decisions regarding their health. Our results suggest that more emphasis should
      be put on properly teaching human physiology in high school, especially to those
      students who do not plan a career in medicine-related fields. This study brings
      to light the disturbing fact that about a year after a student finishes his basic
      physiology course his knowledge of the subject returns to a pre high school
      level.

PMID- 25951694
TI  - [Influence of selected endogenous and environmental factors on the course and
      complications of Grave's disease].
AB  - Graves' disease (GD) is an autoimmune thyroid disease with complex and not fully
      established etiology. It occurs when environmental factors influence people
      genetically prone to this illness. The aim of this study was to determine the
      impact of selected factors (endogenous and environmental) on the course and
      complications of disease in patients with recurrent GD. MATERIALS AND METHODS:
      Two hundred and four patients with relapsed GD, treated in the Clinical
      Department of Endocrinology in University Hospital in Cracow in years 2004-2006
      and then in 2011 were retrospectively analyzed. Patients who agreed to
      participate in the study were sent questionnaire to complete. Demographic and
      clinical data were collected and entered into a database. Patient data included:
      gender, place of living, lifestyle (smoking), family history of autoimmune
      diseases, the course of the disease, its symptoms and the treatment strategy.
      Furthermore the medical documentation was analyzed. Descriptive statistical
      analyses were made. RESULTS: The study showed a significant difference in the
      frequency of appearance of ophthalmopathy between men and women (80% and 37.14%,
      respectively, p = 0.041), between smokers and nonsmokers (61.9% and 21.05%,
      respectively, p = 0.022) and between the age of patients with positive and
      negative family history of autoimmune diseases (37.6 years and 50.5 years
      respectively, p = 0.002). CONCLUSIONS: 1. Male gender is a risk factor for
      ophthalmopathy in GD. 2. Cigarette smoking affects the risk of Graves'
      ophthalmopathy. 3. A positive family history of thyroid diseases and/or
      autoimmune diseases promotes the development of GD at a younger age.

PMID- 25951695
TI  - [Determinants of nonalcoholic fatty liver disease in men and women with type 2
      diabetes].
AB  - Nonalcoholic fatty liver disease (NAFLD) is recognized in 20-30% of general
      population but among the people with impaired glucose metabolism this percentage
      is about 70-90%. The aim of this study is to assess the determinants of NAFLD
      with respect to patients' gender. We examined 180 patients, 73 women and 107 men.
      Increased body mass index (BMI), waist circumference above the norm are the
      determinants of NAFLD irrespectively to gender. Besides it has been observed that
      in the women group the increase of HDL-cholesterol by 1 mmol/l decreases the
      chances of NAFLD occurrence by 90%.

PMID- 25951696
TI  - [Therapeutic results in children with hypoplastic left heart syndrome after
      Norwood procedure].
AB  - Hypoplastic left heart syndrome (HLHS) encompasses hypoplasia or atresia of the
      left ventricle, stenotic or artretic aortic and mitral valves and hypoplasia of
      the ascending aorta. The aim of the 1-st stage operation called the modified
      Norwood procedure is reconstruction of the systemic flow, providing an adequate
      pulmonary flow and relieving interatrial restriction. The aim of the study was
      the analysis of treatment results after the Norwood operation in children
      hospitalized at Cardiology and Cardiac Surgery Departments in the period of 2009
      2012. The material consisted of 65 children (42 males, 23 females). The following
      factors were analyzed: the age on admission, general condition, pre-operative
      clinical course. RESULTS: The mean age of children on admission was 4.4 +/- 4.1
      days and mean body weight--3.3 +/- 0.5 kg. The general condition was good in the
      majority of patients (74%). The remaining children were found to have early
      symptoms of congestive heart failure (CHF). Cardiological and/or surgical
      interventions were necessary in 33 (50.8%) patients, among them three children
      required both procedures. In the majority of patients (n = 21, 32%), the main
      cause of intervention was re-coarctation of the neo-aortic isth- mus treated with
      balloon plasty and/ or stenting. In the early post-operative period, six children
      died due to CHF (n = 4) and infections (n = 2), while the remaining six children
      died due to various complications while waiting for the 2nd stage. CONCLUSIONS:
      Despite the progress in diagnosis and treatment of children with HLHS the
      mortality is still high.

PMID- 25951697
TI  - [Significance of vitamins A and E in the cervical intraepithelial neopiasia-
      CEN].
AB  - Cervical intraepithelial neoplasia--CIN affects women in their repro- ductive
      life period. CIN may proceed squamous cervical cancer. CIN is divided into: CIN1,
      CIN2, CIN3. CIN3 comprises cervical cancer in situ- CIS which is the true
      precancer state within the cervix. CIN, depending on grade may progress, regress
      or persist for many years. According to a few publication vitamins C, E and A may
      protect against carcinogenesis within the cervix. The aim of this paper was
      evalua- tion of vitamins A and E serum concentration of cervical intraepithelial
      neoplasia patients. The study material consisted of 289 women aged 25-60 years
      diagnosed with CIN and early invasive cervical cancer IA. The subjects of the
      study were selected amongst participants of National Cervical Cancer Screen- ing
      Program attending Department of Gynecology and Oncology of Jagiellonian
      University Medical College in Krakow. The control group consisted of 44 women
      aged 28-56 years diagnosed and treated in the same centre and period due to a non
      oncologic gynecologic conditions. Serum vitamin A and E was measured with HPLC
      method with ultraviolet detector (UV) (254 nm). RESULTS: Medium serum vitamin A
      concentration in the study group was 2.67 +/- 1.15 mg/l and was significantly (p
      < 0.001) lower than in control group -3.81 +/- 1.62 mg/l. Mean serum vitamin E
      concentration in the study group was 3.95 +/- 1.93 mg/l and was also
      significantly (p < 0.001) lower than in control group (8.63 +/- 2.84 mg/l). To
      conclude, the observed significantly lower vitamins A and E serum concentrations
      may be related to the cervical neoplasia process. The normal vitamin A and E
      serum levels may have a protective effect against cervical carcinogenesis.

PMID- 25951698
TI  - [The influence of radiotherapy of head and neck cancers on carotid arteries].
AB  - INTRODUCTION: Modern radiotherapy of head and neck cancers involves high dosage
      of radiation per tissue volume including carotid arteries. Little is known about
      the mechanism of influence of radiotherapy to the large carotid arteries it may
      lead to inflammatory condition in the vascular wall, intima-media thickness (IMT)
      of the vessel and increase atherosclerosis. This work is based on current
      knowledge and presents the results of research which is based on ultrasound
      assessment of IMT and atheromatous changes in the carotid artery in a group of 61
      irradiated patients with head and neck tumors. OBJECTIVES: To assess IMT, the
      progression of the atheromatous changes in the carotid arteries of patients who
      had completed radiotherapy in comparison with a control group of non-treated
      patients and to determine the relation between the progression of the
      atheromatous changes, the radiation dosage and time after their radiotherapy.
      PATIENTS AND METHOD: The ultrasound tested carotid arteries of 61 patients. The
      mean of the dose in the carotid area was 50.7 +/- 10.6 Gy, and the time after the
      therapy completion was 41 +/- 27 months. The results were compared with the
      measurement in the control group--62 people of similar age and risk of
      atherosclerosis. The stenosis was assessed using planimetric and hemodynamic
      methods and the structure of the plaque was assessed according to Gray-Weale.
      RESULTS: The average size of IMT on the front wall of the common carotid artery
      (CCA) is significantly bigger than on the opposite wall, p = 0.0149. There was
      shown no statistic difference concerning the average size of IMT (assessed on the
      posterior wall of the arteries) between the group of patients after radiotherapy
      and the control group (p = 0.1877). It has been proven that the frequency of
      occurrence of plaque in the carotid arteries in the patients who had completed
      radiotherapy compared to the control group is 16.3% bigger. The dominant type of
      plaque in the group of patients who had completed radiotherapy are heterogeneous
      plaques with majority of low echoes Type 2 or high echoes Type 3. The surface of
      the plaque in the group of patients is mostly irregular in comparison with the
      control group. There is no relationship between the thickness of IMT and the size
      of dosage. However, when considering the age of the patients there is an increase
      of IMT depending on the radiation dosage. It has been proven that the increase of
      IMT for patients below 63 years of age is bigger than for patients over 63. In
      the last statistical analysis, which studied the influence of time after the
      termination of treatment on the IMT, it has been proven that there is a small
      correlation of there parameters but not significant from the statistical point of
      view. CONCLUSION: The results of the research show that radiotherapy influences
      large carotid arteries by accelerating the IMT in the younger age group below 63
      years of age. Radiation increases the frequency of plaque in carotid ateries and
      the creation of plaque of heterogeneous structure. Understanding the increase of
      IMT and the presence of hemodynamically important atherosclerosis as a
      significant risk factor for cerebro-vascular accident we need to consider the
      introduction of ultrasound scan as a routine test in the assessment of carotid
      arteries in patients who had completed radiotherapy to the head and neck area.

PMID- 25951699
TI  - Oncological emergencies: superior vena cava syndrome.
AB  - Superior vena cava obstruction leads to the venous hypertension of the head,
      neck, upper extremities and upper part of the truncus. Its clinical
      manifestation, known as the superior vena cava syndrome, is a complication of
      malignancy, mainly of lung cancer and lymphoma. As it usually affects patients
      with advanced disease, the prognosis is poor. This article stresses the
      importance of early detection and adequate management of this onco- logical
      emergency. The diagnostic tools as well as treatment possibilities are discussed.

PMID- 25951700
TI  - [Iatrogenic ureteral injury in adults--diagnosis and treatment].
AB  - Ureteral injuries are rare and a special group are iatrogenic ureteral injury.
      Such a situation may occur during open surgery, laparoscopic surgery and
      endoscopy. The mechanism typically includes cutting or ligation of the ureter or
      combination of both what may lead to urinary retention and tissue infiltration by
      urine. The priority is to prevent the incidence of injury. Even 75% of ureteral
      damage can be not identified during the surgery, when the injury occurred. The
      basis of treatment is to drain the urine, the urine leakage and ureter
      reconstruction.

PMID- 25951701
TI  - [The influence of long-term care on the health of caregivers of Alzheimer's
      disease patients].
AB  - The literature indicates that caregivers of patients with Alzheimer's disease
      experience a significant degree of burden that impacts on their health-related
      quality of life (HRQOL). AD caregivers experience significant changes in a
      social, family and professional life depending on diverse factors. Caring for a
      patient with dementia directly links to significant psychological stress. It also
      affects the caregivers' physical and mental health. The psychiatric morbidity is
      higher among the caregivers population. Depression, anxiety disorder and insomnia
      have been found to be the most common. The burden and the negative changes
      experienced by the caregivers predispose the lower quality of care and premature
      institutionalisation of AD patients. Excessive burden experienced by carers
      increases their rate of patients neglect and abuse. Life quality improvement
      becomes the main target of the proper care giving system.

PMID- 25951702
TI  - [The parameters of ovarian reserve and their usefulness to assess the present and
      future woman's fertility].
AB  - It is well-known fact, that recently women decide to have a baby much later than
      previously. However after reaching 35 years old the woman's fertility reduces
      considerably. The effect of this phenomenon causes the increase of assisted
      reproductive technology (ART) treatment. Using of endocrinological, visual and
      genetic test combinations should assess the ovarian reserve and success of ART
      procedure. These tests could be used for estimation of approximate fertility of
      woman in future and for choice of the optimal time for having a baby.

PMID- 25951703
TI  - [Diabetes insipidus].
AB  - Diabetes insipidus is an uncommon disorder of water-electrolyte balance
      characterized by the excretion of abnormally large volumes of diluted urine
      (polyuria) and increased fluid intake (polydipsia). The disease may result from
      the insufficient production of vasopressin, its increased degradation, an
      impaired response of kidneys to vasopressin, or may be secondary to excessive
      water intake. Patients with severe and uncompensated symptoms may develop marked
      dehydration, neurologic symptoms and encephalopathy, and therefore diabetes
      insipidus can be a life-threatening condition if not properly diagnosed and
      managed. Patients with diabetes insipidus require treatment with desmopressin or
      drugs increasing sensitivity of the distal nephron to vasopressin, but this
      treatment may be confusing because of the disorder's variable pathophysiology and
      side-effects of pharmacotherapy. This review summarizes the current knowledge on
      different aspects of the pathophysiology, classification, clinical presentation,
      diagnosis, and management of diabetes insipidus. The reader is also provided with
      some practical recommendations on dealing with patients suffering from this
      disease.

PMID- 25951704
TI  - [Contemporary place of the electroconvulsive therapy Part 1. The historical
      context arnd the biological basis].
AB  - Electroconvulsive therapy (ECT) is a former physical therapy method in psychiatry
      which is applicable up till today in relation to its high effectiveness and the
      safety. Centuries of applying nonconvulsive methods of the electric stimulation
      preceded introducing this method into the clinical practice. ECT is arousing a
      lot of controversies; populous myths are connected with its applying--that
      demands explanations. Numerous biological mechanisms explaining the clinical
      efficacy of ECT action are well-known.

PMID- 25951705
TI  - [Reccurent Clostridium difficile infection in patient after kidney
      transplantation on rituximab therapy due to PTLD (Post-Transplant
      Lymphoprolipherative Disorder). First experience with Fidaxomicin use--case
      report].
AB  - Clostridium difficile infection (CDI) is an increasingly problem in everyday
      clinical practice. The most important risk factor of this infection is
      antibiotics use. The incidence of Clostridium difficile associated diarrhea
      (CDAD) in patients after renal transplantation is estimated to be about 6% in the
      early postoperative period. Due to the applied immunosuppression and frequent
      infections requiring intensive, broad spectral antibiotics, the later prevalence
      of CDAD may remain at a similar level. Massive diarrhea caused by Clostridium
      difficile may lead to fluctuations in immunosuppressive drugs concentration, in
      renal transplant patients. The authors present a case study of a 23-year old
      patient after kidney transplantation from deceased donor, with diagnosed
      polymorphic PTLD (Post-Transplant Lymphoproliferative Disorder). During
      biological treatment with rituximab in this patient 4 recurrences of CDI were
      observed. In this article the clinical manifestation of recurrent CDAD are
      presented. The authors discuss therapeutic procedure with fidaxomicin use, its
      results and influence on immunosuppressive drugs concentration.

PMID- 25951706
TI  - [History of medicine by prof. Sebastian Girtlera].
AB  - Sebastian Girtler (1767-1833), who later became rector of the Jagiellonian
      University is known primarily as a lecturer and author of several works of
      forensic medicine, police attention and veterinary medicine. Not so often we hear
      of him as a historian of medicine, subject of Girtler's interests, which had a
      lot of his attention and work. This text, to a significant extent based on
      archival materials, seeks to reconstruct the teaching program and analyses the
      content and methodology of the two works directly related to past of medical
      sciences, which had been written by Girtler himself.

PMID- 25951707
TI  - Regeneration of Articular Cartilage Surface: Morphogens, Cells, and Extracellular
      Matrix Scaffolds.
AB  - The articular cartilage is a well-organized tissue for smooth and friction-free
      joint movement for locomotion in animals and humans. Adult articular cartilage
      has a very low self-regeneration capacity due to its avascular nature. The
      regeneration of articular cartilage surface is critical to prevent the
      progression to osteoarthritis (OA). Although various joint resurfacing procedures
      in experimental articular cartilage defects have been developed, no standardized
      clinical protocol has yet been established. The three critical ingredients for
      tissue regeneration are morphogens and growth factors, cells, and scaffolds. The
      concepts based on the regeneration triad have been extensively investigated in
      animal models. However, these studies in animal models have demonstrated variable
      results and outcomes. An optimal animal model must precisely mimic and model the
      sequence of events in articular cartilage regeneration in human. In this article,
      the progress and remaining challenges in articular cartilage regeneration in
      animal models are reviewed. The role of individual morphogens and growth factors
      in cartilage regeneration has been investigated. In normal articular cartilage
      homeostasis, morphogens and growth factors function sequentially in tissue
      regeneration. Mesenchymal stem cell-based repair of articular cartilage defects,
      performed with or without various growth factors and scaffolds, has been widely
      attempted in animal models. Stem cells, including embryonic and adult stem cells
      and induced pluripotent stem cells, have also been reported as attractive cell
      sources for articular cartilage surface regeneration. Several studies with regard
      to scaffolds have been advanced, including recent investigations based on
      nanomaterials, functional mechanocompatible scaffolds, multilayered scaffolds,
      and extracellular matrix scaffolds for articular cartilage surface regeneration.
      Continuous refinement of animal models in chondral and osteochondral defects
      provide opportunities that support further advances in tissue engineering for the
      optimal articular cartilage surface regeneration. 

PMID- 25951708
TI  - The influence of sintering conditions on microstructure and mechanical properties
      of titanium dioxide scaffolds for the treatment of bone tissue defects.
AB  - In this study the attempts to improve mechanical properties of highly-porous
      titanium dioxide scaffolds produced by polymer sponge replication method were
      investigated. Particularly the effect of two-step sintering at different
      temperatures on microstructure and mechanical properties (compression test) of
      the scaffolds were analysed. To this end microcomputed tomography and scanning
      electron microscopy were used as analytical methods. Our experiments showed that
      the most appropriate conditions of manufacturing were when the scaffolds were
      heat-treated at 1500  degrees C for 1 h followed by sintering at 1200  degrees C
      for 20 h. Such scaffolds exhibited the highest compressive strength which was
      correlated with the highest linear density and the lowest size of grains.
      Moreover, grain size distribution was narrower with predominating fraction of
      fine grains 10-20 MUm in size. Smaller grains and higher linear density sug-
      gested that in this case densification process prevailed over undesirable process
      of grain coarsening, which finally resulted in im- proved mechanical properties
      of the scaffolds. 

PMID- 25951709
TI  - Pilot study special AT-rich sequence-binding protein 1 investigating as a
      potential biomarker for esophageal squamous cell carcinoma.
AB  - In the present study, we aimed to evaluate the expression of special AT-rich
      sequence-binding protein 1 (SATB1) in esophageal squamous cell carcinoma (ESCC)
      and assess the correlation between its expression and the clinicopathological
      features and prognosis of the disease. SATB1 expression in ESCC tissue was
      determined by using immunohistochemical analysis, quantitative real-time
      polymerase chain reaction, and western blot analysis. The relationship between
      SATB1 expression and clinicopathological features was examined by using the chi
      squared test, and the survival rate was calculated by using the Kaplan-Meier
      survival curve. The correlation between the indicators and patient survival was
      estimated by using a Cox regression analysis. High SATB1 expression in was
      detected in 48.3% and 7.8% of ESCC and normal esophagus tissues (P < 0.05),
      respectively. SATB1 expression did not significantly correlate with
      clinicopathological features. The Kaplan-Meier curve indicated that patients with
      high SATB1 expression had significantly shorter survival than those with low
      SATB1 expression. In a multivariate Cox regression model, high SATB1 expression
      was identified as an independent prognostic factor for patients with ESCC. In
      conclusion, these results suggest that high SATB1 expression is predictive of
      poor prognosis in ESCC and may be a promising new candidate for targeted
      therapies for ESCC. 

PMID- 25951710
TI  - Noninvasive prenatal testing for fetal trisomy in mixed risk factors pregnancy
      population.

PMID- 25951711
TI  - Readers' comment is important for the journal.

PMID- 25951712
TI  - Clinical cancer chemoprevention: From the hepatitis B virus (HBV) vaccine to the
      human papillomavirus (HPV) vaccine.
AB  - Approximately 2 million new cancer cases are attributed to infectious agents each
      year worldwide. Vaccines for the hepatitis B virus (HBV), a risk factor of
      hepatocellular cancer, and human papillomavirus (HPV), a risk factor of cervical
      cancer, are considered major successes in clinical chemoprevention of cancer. In
      Taiwan, the first evidence of cancer prevention through vaccinations was provided
      by HBV vaccination data in infants. The Taiwanese HBV vaccination program has
      since become a model immunization schedule for newborns worldwide. Persistent
      infection with high-risk HPV is generally accepted as prerequisite for cervical
      cancer diagnosis; however, cervical cancer is a rare complication of HPV
      infections. This is due to the fact that such infections tend to be transient.
      The safety and efficacy of both available HPV quadrivalent vaccine and bivalent
      vaccine are not in doubt at the present time. Until a human cytomegalovirus (CMV)
      vaccine becomes available, simple hygienic practices, such as hand washing, can
      prevent CMV infection both before and during pregnancy. Each country should
      establish her official guidelines regarding which vaccines should be used to
      treat various conditions, the target population (i.e., universal or limited to a
      selected population), and the immunization schedules. After a vaccine is
      recommended, decisions regarding reimbursement by the public health care fund are
      evaluated. The guidelines become part of the immunization schedule, which is
      updated annually and published in the official bulletin. In conclusion, both HBV
      and HPV vaccines are considered major successes in the chemoprevention of cancer.

PMID- 25951713
TI  - Usefulness of chewing gum for recovering intestinal function after cesarean
      delivery: A systematic review and meta-analysis of randomized controlled trials.
AB  - Chewing gum has been reported to enhance bowel function. However, the efficacy
      remains unclear for women undergoing cesarean delivery. The aim of this meta
      analysis is to evaluate the efficacy of chewing gum for recovering intestinal
      function following cesarean delivery in the early postoperative period.
      Electronic databases including MEDLINE, EMBASE, Cochrane Library were searched to
      identify English language randomized controlled trials comparing chewing gum with
      other procedures for promoting the recovery of intestinal function after cesarean
      delivery. Two of the authors independently extracted data from the eligibility
      studies, and Review Manager Version 5.2 was used to pool the data. Finally, five
      randomized controlled trials involving 882 patients were included and all the
      trials were considered as at high risk of bias. The pooled findings showed that
      chewing gum after cesarean delivery can significantly shorten the time to first
      flatus [standardized mean difference (SMD) = -0.73; 95% confidence interval (CI)
      = -1.01 to -0.14; p < 0.001]; time to first hearing of normal intestinal sounds
      (SMD = -0.69; 95% CI = -1.20 to -0.17; p = 0.009; I2 = 92%). Time to the first
      defecation (SMD = -0.53; 95% CI = -1.61 to -0.07; p = 0.07; I2 = 92%) and length
      of hospital stay (SMD = -0.59; 95% CI = -1.18 to 0.00; p = 0.05; I2 = 93%) were
      also reduced in the chewing gum group; however, these results were not
      statistically significant. The current evidence suggests that chewing gum has a
      positive effect on intestinal function recovery following cesarean delivery in
      the early postoperative period. However, more large-scale and high-quality
      randomized controlled trials are needed to confirm these results.

PMID- 25951714
TI  - Noninvasive prenatal testing for fetal trisomy in a mixed risk factors pregnancy
      population.
AB  - OBJECTIVE: This study assesses the performance of noninvasive prenatal testing
      (NIPT) for fetal aneuploidies in a mixed risk factors pregnancy population.
      MATERIALS AND METHODS: Data review of 169 pregnant women undergoing prenatal
      aneuploidy screening in a single tertiary medical center was conducted.
      Indications included maternal anxiety, advanced maternal age, abnormal nuchal
      translucency, and high/moderate risk of first trimester Down syndrome screening.
      Multifetal pregnancies and patients receiving in vitro fertilization were also
      enrolled for analysis. RESULTS: A total of 169 patients were enrolled in this
      study during a time period from July 2012 to June 2014. For patients' >= 34
      years, anxiety about amniocentesis was the most common reason for patients
      selecting NIPT for fetal aneuploidy screening, with 107 (88.4%) patients choosing
      NIPT for this reason. Among the total patient population, two patients showed a
      positive result from NIPT. One patient displayed 47, XXY, which was confirmed to
      be a false-positive result. The other patient displayed trisomy 18, which was
      confirmed by an amniotic cell culture. The sensitivity for NIPT is 100% with the
      specificity 99.4%. CONCLUSIONS: NIPT for fetal aneuploidy in a mixed risk factors
      pregnancy population showed high accuracy. NIPT applied to the low risk
      population might reassure the anxious family.

PMID- 25951715
TI  - Novel markers in the diagnostics of endometriomas: Urocortin, ghrelin, and leptin
      or leukocytes, fibrinogen, and CA-125?
AB  - OBJECTIVE: CA-125 protein is used as a marker in clinical practice for the
      diagnosis of endometriomas. The aim of this study was to determine whether
      endometriomas are accompanied by an increased level of urocortin, ghrelin, and
      leptin, as well as the increased parameters of blood cell count, fibrinogen, and
      CA-125. MATERIALS AND METHODS: The study included 86 women aged 18-38 years who
      had been treated laparoscopically for lesions in the adnexa with the
      characteristics of endometriomas and mature teratoma, during the period September
      2009 to November 2012. The statistical analysis was performed using the
      nonparametric Mann-Whitney U test and the Spearman rank correlation coefficients
      (p <= 0.05). RESULTS: The medians were 105.31 pg/mL versus 120.84 pg/mL for
      urocortin, 7.16 pg/mL versus 9.13 pg/mL for leptin and 584.33 pg/mL versus 657.82
      pg/mL for ghrelin (p > 0.05), respectively. Analyzing the parameters of blood
      cell count, statistically significant differences were shown in the respective
      groups for leucocyte level (5.35 * 10(9)/L vs. 6.7 * 10(9)/L; p = 0.029),
      fibrinogen level (3.12 mg% vs. 2.57 mg%; p = 0.001), and CA-125 (36.50 U/mL vs.
      15.08 U/mL; p = 0.001). CONCLUSION: In conclusion, the prognostic values for CA
      125, leukocytes, and fibrinogen may prove a very useful tool for the diagnosis of
      lesions in the adnexa of the type endometriomas.

PMID- 25951717
TI  - Maternal hyperglycemia and the 100-g oral glucose tolerance test.
AB  - OBJECTIVES: To compare the characteristics of pregnant women with hyperglycemia
      according to the severity of glucose intolerance using the 100-g oral glucose
      tolerance test (OGTT) and to demonstrate the need to manage the condition of
      women with mild hyperglycemia. MATERIALS AND METHODS: In this retrospective
      cohort study, a total of 258 women at high risk of gestational diabetes (GDM)
      based on a positive 50-g oral glucose challenge test (OGCT) were classified into
      0+, 1+, 2+, 3+, and 4+ groups according to the number of abnormal plasma glucose
      values on the 100-g OGTT. The clinical characteristics of the groups were
      compared. RESULTS: The rates of advanced maternal age (>= 35 years), multiparity,
      prior history of GDM, preterm birth, cesarean delivery, and elevated body mass
      index were all positively correlated with the number of abnormal plasma glucose
      values on the OGTT (p < 0.05 for all variables). After adjusting for confounding
      factors, the fasting plasma glucose levels predicted birth weight in 44.4%,
      48.4%, and 58.6% of the women in the positive 50-g OGCT group, the 0+ group, and
      the 1+ group, respectively. Weight gain during pregnancy predicted birth weight
      in 42%, 44.6%, and 37.6% of the women in the positive 50-g OGCT group, the 0+
      group, and the 2+ group, respectively (p < 0.001 in each case). CONCLUSIONS:
      These data demonstrate that the detection and management of mild hyperglycemia
      below the current diagnostic criteria of GDM as well as GDM diagnosed using the
      100-g OGTT are necessary for improving pregnancy outcomes.

PMID- 25951716
TI  - Effects of dehydroepiandrosterone supplementation on women with poor ovarian
      response: A preliminary report and review.
AB  - OBJECTIVE: To investigate the effect of dehydroepiandrosterone (DHEA)
      supplementation on women with poor ovarian response (POR). MATERIALS AND METHODS:
      Women with POR treated with flexible daily gonadotropin-releasing hormone
      antagonist in vitro fertilization (IVF) cycles at The Reproductive Center in
      Kaohsiung Veterans General Hospital between January 2013 and October 2013, were
      enrolled for this prospective study. When patients failed to become pregnant
      during the first IVF cycle, they were treated with DHEA supplementation (30 mg, 3
      times a day, orally) for 3 months (mean 12.2 weeks) before the next IVF cycle.
      Parameters of biochemical, ultrasound and treatment outcomes were compared before
      and after DHEA supplementation. RESULTS: Ten patients with a mean age of 36.6 +/-
      4.2 years were identified. After DHEA treatment, there was a significant increase
      in antral follicle count, from 2.8 +/- 1.0 to 4.1 +/- 1.2 (p < 0.05), and anti
      Mullerian hormone, from 0.4 +/- 0.2 ng/mL to 0.84 +/- 0.2 ng/mL (p < 0.001). A
      significant decrease of Day 3 follicle-stimulating hormone and estradiol, from
      14.4 +/- 1.7 mIU/mL to 10.1 +/- 0.7 mIU/mL and from 51.2 +/- 6.3 pg/mL to 35.2 +/
      4.2 pg/mL, respectively (both p < 0.001), was noted. Increased numbers of
      retrieved oocytes (from 2.4 +/- 1.1 to 4.2 +/- 1.2; p < 0.01), fertilized oocytes
      (from 1.7 +/- 0.5 to 3.8 +/- 1.1; p < 0.001), Day 3 embryos (from 1.7 +/- 0.5 to
      3.7 +/- 1.1; p < 0.001) and transferred embryos (from 1.7 +/- 0.8 to 2.8 +/- 0.8;
      p < 0.01) were also seen in these women with POR after DHEA treatment. Three
      women became pregnant after DHEA treatment. CONCLUSION: The potential benefits of
      DHEA supplementation in women with POR were suggested by the biochemical
      parameters and IVF outcomes.

PMID- 25951718
TI  - Immunomodulatory therapy in refractory/recurrent ovarian cancer.
AB  - OBJECTIVE: To investigate the efficacy and toxicity of immunomodulatory therapy
      (IMT) alone or as an add-on to palliative/salvage chemotherapy in patients with
      refractory/recurrent epithelial ovarian cancer (EOC). MATERIALS AND METHODS: We
      retrospectively analyzed the efficacy and toxicity of IMT in 15 patients with
      refractory/recurrent EOC who had previously received multiple chemotherapy
      regimens. RESULTS: The median age of the patients was 56 years (range, 41-75
      years). Three patients were platinum-sensitive, two were platinum-resistant, and
      the remaining 10 patients were refractory to platinum-based front-line
      chemotherapy. IMT consisted of picibanil (OK-432) on Day 1, interleukin-2 and/or
      interferon-alpha on Day 2 administered by subcutaneous injection (every week or 2
      weekly). Five patients never received metronomic oral cyclophosphamide. After
      IMT, three patients achieved partial remission (PR, lasting for 11 months, >= 12
      months, and 16 months), and six patients had stable disease (SD). The disease
      stabilizing rate (PR+SD) was 60% (3/3 in platinum-sensitive and 6/12 in platinum
      resistant/refractory patients). The absolute lymphocyte count (ALC) at 1 month
      after IMT was significantly higher in the PR+SD group (median 1242.0/MUL) than in
      the progression group (median 325.0/MUL) (p = 0.012). No >= Grade 3 toxicities
      were observed. The median post-IMT survival time was 12 months (range, 2-39
      months). CONCLUSION: IMT alone or add-on to palliative/salvage chemotherapy for
      refractory/recurrent EOC achieves a substantial disease stabilizing rate without
      severe toxicity, which might be a potential option in selected patients. The ALC
      1 month after IMT could be an early indicator to disease stabilization.

PMID- 25951719
TI  - Is laparoendoscopic single-site surgery (LESS) retroperitoneal hysterectomy
      feasible?: Surgical outcomes of the initial 27 cases.
AB  - OBJECTIVES: The aim of the present study was to determine the feasibility of
      retroperitoneal hysterectomy by laparoendoscopic single-site surgery (LESS) and
      to suggest technical tips. MATERIALS AND METHODS: This study is a prospective
      single-center study. One surgeon trained in minimally invasive surgery performed
      LESS retroperitoneal hysterectomy on 27 consecutive patients with symptomatic
      uterine myomas or adenomyosis between September 2012 and February 2013. LESS
      retroperitoneal hysterectomy requires an additional eight steps including
      development of the retroperitoneal space, dissection of the ureter, and ligation
      of the uterine artery where it originates from the internal iliac artery.
      RESULTS: LESS retroperitoneal hysterectomies were successfully performed in 23
      (85.2%) patients. Of the four failed cases, three failed to develop the
      retroperitoneal space because of laterally located large myomas. Another patient
      with severe pelvic adhesion was converted to multiport laparoscopic vaginal
      hysterectomy. Total operative and bilateral uterine ligation time by the
      retroperitoneal approach was 84 (67.0-95.6) minutes and 16 (12-22) minutes,
      respectively. The median estimated blood loss was 150 (100-350) mL. One patient
      required postoperative transfusion. No other operative complications including
      ureteric injury were observed during the hospital stay or the 3-month follow-up
      period after discharge. CONCLUSION: LESS retroperitoneal hysterectomy is feasible
      and can be a good option.

PMID- 25951720
TI  - Clinical outcomes and development of children born to couples with obstructive
      and nonobstructive azoospermia undergoing testicular sperm extraction
      intracytoplasmic sperm injection: A comparative study.
AB  - OBJECTIVE: To evaluate and compare the clinical outcomes and development of
      children born between obstructive azoospermia (OA) couples and nonobstructive
      azoospermia couples (NOA) after testicular sperm extraction (TESE) and
      intracytoplasmic sperm injection (ICSI). MATERIALS AND METHODS: Data were
      collected from infertile couples suffering from azoospermia who underwent TESE
      and ICSI from January 2001 to December 2009 at Chang Gung Memorial Hospital,
      Taiwan. A total of 154 ICSI cycles were performed using extracted testicular
      sperm from men with obstructive azoospermia (67 ICSI cycles) and men with
      nonobstructive azoospermia (87 ICSI cycles). Retrospective analysis of clinical
      outcomes and development of children born after TESE-ICSE between obstructive
      azoospermia couples and nonobstructive azoospermia couples. RESULTS: The assisted
      reproductive technology (ART) result between OA and NOA groups, including age, E2
      level on hCG day, number of oocytes retrieved, normal fertilization rate, zygote
      Grade 1 score distribution, number of top-quality embryos transferred, clinical
      pregnancy rate per transfer, chemical pregnancy rate per transfer, implantation
      rate, live birth rate per transfer, and abortion rate per transfer, were all
      similar. Thirty-one live births resulted from 67 ICSE cycles in the OA group and
      33 live births from 87 ICSE cycles in the NOA group. The obstetric and perinatal
      outcomes were similar between the groups, and children conceived by using ICSI
      were generally healthy without raised tendency of major birth defect and
      development impairment. CONCLUSION: In our study, there were no differences in
      the fertility rate and clinic pregnancy rate between the OA and NOA groups using
      TESE-ICSI. Also, the clinical outcomes and development of children were similar
      between the OA and the NOA groups using TESE-ICSI.

PMID- 25951722
TI  - The reliability of transabdominal cervical length measurement in a low-risk
      obstetric population: Comparison with transvaginal measurement.
AB  - OBJECTIVE: To determine the correlation between transabdominal (TA) and
      transvaginal (TV) cervical length measurement in a low-risk obstetric population
      in Taiwan. MATERIALS AND METHODS: Women with a singleton pregnancy between 20
      weeks and 24 weeks of gestation underwent postvoid TA and TV cervical length
      measurements. Differences between the measurements obtained using the two methods
      were evaluated. RESULTS: Two hundred and five women agreed to participate in the
      study. Paired TA and TV measurements were obtained in 174 women. The mean TA
      cervical length was 36.0 +/- 4.9 mm and the mean TV cervical length was 37.6 +/-
      5.4 mm. The mean TA cervical length was shorter than the mean TV cervical length
      by 1.6 mm. The 5(th) percentile of TA and TV cervical length was 29 mm and 29.1
      mm, respectively. The discrepancies between the two methods were not
      significantly correlated with maternal body mass index (BMI). All women with TV
      cervical length <25 mm had a corresponding TA cervical length <29 mm. CONCLUSION:
      The TA cervical length could be obtained in the majority of the low-risk pregnant
      women in the present study, and the TA cervical length was closely correlated
      with the TV cervical length. The use of TA ultrasound could be an effective
      initial tool for cervical length screening in low-risk pregnant women. TA
      cervical length <29 mm (5(th) percentile) could be used as a cut-off value for
      further TV ultrasound.

PMID- 25951721
TI  - Evaluation of maternal systemic inflammatory response in preeclampsia.
AB  - OBJECTIVE: To evaluate the systemic inflammatory response in preeclampsia
      compared to normal pregnancy. MATERIALS AND METHODS: The following serum
      parameters were determined in three groups of patients: leukocytes, neutrophils,
      tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), C-reactive protein
      (CRP), and certain markers of oxidative stress. Fetal status was assessed based
      on the gestational age at which birth occurred, on the Apgar score, and on fetal
      weight. RESULTS: In preeclampsia, a higher systemic inflammatory status was found
      compared to normal pregnancy. Gestational age at birth, fetal weight, and Apgar
      score were significantly lower in the group with preeclampsia compared to normal
      pregnancy. CONCLUSION: In preeclampsia, there is an increased systemic
      inflammatory response compared to normal pregnancy, which can influence fetal
      status at birth.

PMID- 25951723
TI  - Clinical outcome affected by tumor morcellation in unexpected early uterine
      leiomyosarcoma.
AB  - OBJECTIVE: To evaluate the influence of morcellation during surgery on clinical
      outcome in unexpected early uterine leiomyosarcomas (LMSs) using a tumor-size
      matched comparison study. MATERIALS AND METHODS: We retrospectively reviewed the
      clinicopathological characteristics, prognostic factors, and treatment outcomes
      of patients with Stage 1 uterine LMS from April 1993 to April 2014 in a
      university-based tertiary hospital. Patients who received morcellation via
      abdomen, vagina, or laparoscopy were compared with tumor-size-matched patients
      who underwent total hysterectomy without morcellation. RESULTS: In total, 34
      consecutive patients were identified, including 14 patients with morcellation and
      20 patients without morcellation. There were no significant difference between
      the two groups of patients in age, parity, mitotic count, lymph node dissection,
      and adjuvant therapy. Six (42.9%) patients with morcellation were reoperated at
      18.5 days after the initial surgery. Tumor recurrence rates at local and distant
      sites showed no difference between the two groups of patients. Patients with
      morcellation had a marginally lower disease-free survival (DFS) and overall
      survival (OS) rates compared with patients without morcellation. In univariate
      analysis, morcellation was marginally significantly associated with lower DFS
      [hazard ratio (HR), 2.62; 95% confidence interval, 0.89-7.71; p = 0.08] and OS
      (HR, 2.70; 95% confidence interval, 0.89-8.20; p = 0.08). In multivariate
      analysis, morcellation was associated with lower OS in marginal significance (HR,
      2.94; 95% confidence interval, 0.83-10.39; p = 0.09). CONCLUSION: Tumor
      morcellation did not increase the abdominal-pelvic recurrence rate, but may be
      associated with lower DFS and OS in Stage 1 LMS.

PMID- 25951724
TI  - Intensive systemic chemotherapy is effective against recurrent malignant Brenner
      tumor of the ovary: An analysis of 10 cases within a single center.
AB  - OBJECTIVE: Malignant Brenner tumors (MBTs) of the ovary are very rare, and their
      definition, biology, and treatment modality have not been established. This study
      investigated the clinical characteristics of MBTs and the importance of
      chemotherapy for recurrent disease. MATERIALS AND METHODS: We conducted a
      retrospective analysis of 10 patients with MBT of the ovary treated at a single
      tertiary center from 1991 to 2013. RESULTS: The median age was 55.5 years (range,
      37-68 years). Nine of the 10 patients were symptomatic. The median size of the
      ovarian tumors was 10.5 cm (range, 2.5-25.0 cm). The cancer antigen-125 level was
      elevated in three patients. Six patients had a stage I tumor, one had a stage II
      tumor, two had a stage III tumor, and one had a stage IV tumor. Six patients
      received systemic adjuvant chemotherapy after surgery. The mean follow-up
      duration was 54.5 months (range, 8-173 months). Disease recurrence occurred in
      four of the 10 patients. The median time to recurrence was 11 months (range, 9-18
      months). Two patients with locoregional recurrence showed favorable results after
      chemotherapy, regardless of the initial stage of the tumor. The patient with the
      stage IIIC tumor is alive at 13 months after recurrence on current chemotherapy.
      The patient with the stage IV tumor showed no evidence of the disease > 12 years
      after the last chemotherapy. Lastly, two patients with distant recurrence died
      after showing a long-term survival of 49 months and 88 months, respectively,
      after recurrence and intensive chemotherapy. CONCLUSION: Our results showed that
      systemic chemotherapy is beneficial in patients with recurrence of a primary MBT
      of the ovary, especially in the locoregional recurrence.

PMID- 25951725
TI  - High grade serous ovarian carcinoma with serous tubal intraepithelial carcinoma
      in a case presented with atypical glandular cell favor neoplasm cervical cytology
      and dermatomyositis.
AB  - OBJECTIVE: This report describes a case of serous ovarian carcinoma with occult
      serous tubal intraepithelial carcinoma (STIC), which presented as atypical
      glandular cells favor neoplasia (AGC-FN) with Pap cytology and dermatomyositis.
      CASE REPORT: A 48-year-old woman presented with symptoms of dermatomyositis. An
      AGC-FN result from a Pap smear, with an absence of a cervical or endometrial
      lesion was noted. After cancer surveillance, ovarian high grade serous carcinoma
      associated with serous tubal intraepithelial carcinoma was diagnosed. Two weeks
      following surgical excision of the carcinoma, dramatic remission of the
      dermatomyositis symptoms was evident. CONCLUSION: The patient had serous
      carcinoma of the ovary with tubal STIC, which presented as dermatomyositis. The
      AGC-FN identified from a Pap smear hinted at a diagnosis of ovarian carcinoma.
      These presentations point to an occult malignancy in the genital tract and demand
      careful diagnostic workup.

PMID- 25951726
TI  - Use of intra-arterial nitroglycerin during uterine artery embolization for severe
      postpartum hemorrhage with uterine artery vasospasm.
AB  - OBJECTIVE: Uterine artery embolization (UAE) is a standard method for treating
      postpartum hemorrhage (PPH), although uterine artery vasospasm during UAE may
      lead to failure of hemostasis. Here, we report our experience with a case of PPH
      in which the bleeding was successfully controlled by intra-arterial
      administration of nitroglycerin during the second UAE. CASE REPORT: A 30-year-old
      woman experienced PPH following a successful cesarean section, and a UAE was
      performed. However, 6 hours later, vaginal bleeding restarted; the reason for
      unsuccessful embolization during the first UAE was vasoconstriction due to
      hypovolemic shock. We performed a second UAE, but uterine bleeding continued.
      After intra-arterial administration of nitroglycerin, hemostasis was confirmed,
      and there was no reperfusion of the uterine artery. After these two UAE
      procedures, no recurrence of bleeding was observed. CONCLUSION: Thus, use of
      intra-arterial nitroglycerin was effective for controlling uterine artery
      vasospasm during UAE. However, larger studies are required to confirm these
      findings.

PMID- 25951727
TI  - Uterine artery embolization, not cesarean section, as an option for termination
      of pregnancy in placenta previa.
AB  - OBJECTIVE: To summarize our experiences in the treatment of labor induction in
      placenta previa using uterine artery embolization. CASE REPORT: We
      retrospectively analyzed the clinical data of seven patients with placenta previa
      who underwent antepartum uterine artery embolization before vaginal delivery.
      After antepartum embolization, five patients with placenta previa had successful
      vaginal deliveries and two cases of placenta previa with accreta underwent
      emergency hysterectomy. Some complications were reported in this experience. The
      follow-up study showed that most patients resumed their normal menstruation and
      some of them were able to conceive. CONCLUSION: For the management of placenta
      previa, uterine artery embolization is a minimally invasive technique that helps
      to avoid cesarean section. The impact on menstruation and fertility is yet to be
      seen.

PMID- 25951728
TI  - First-trimester diagnosis of recurrent omphalocele associated with fetal trisomy
      18 but without parental mosaicism.

PMID- 25951729
TI  - Myomectomy of a massive uterine myoma during cesarean section under regional
      anesthesia.

PMID- 25951730
TI  - Spontaneous rupture and massive hemoperitoneum from uterine leiomyomas and
      adenomyosis in a nongravid and unscarred uterus.

PMID- 25951731
TI  - Advanced endocervical adenocarcinoma metastatic to the ovary presenting as
      primary ovarian cancer.

PMID- 25951733
TI  - Alternative management of a sizable cul-de-sac ectopic pregnancy.

PMID- 25951732
TI  - Prenatal diagnosis of mosaic tetrasomy 9p in a fetus with isolated persistent
      left superior vena cava.

PMID- 25951734
TI  - Cesarean scar pregnancy: What can we offer?

PMID- 25951735
TI  - Isolated Krukenberg tumor in pregnancy.

PMID- 25951736
TI  - An echo of an important but often neglected issue-late preterm births.

PMID- 25951737
TI  - Introduction. Breast Cancer.

PMID- 25951738
TI  - Breast cancer prevention across the cancer care continuum.
AB  - OBJECTIVES: To review the current state of breast cancer prevention from primary
      prevention through survivorship, highlight cross-cutting issues, and discuss
      strategies for clinical integration and future research. DATA SOURCES: Published
      articles between 1985 and 2015 and original research. CONCLUSION: Cancer risk
      persists across the lifespan. Interprofessional strategies to reduce morbidity
      and mortality from cancer include primary, secondary, and tertiary prevention
      (survivorship). Prevention strategies across the cancer care continuum are cross
      cutting and focus on measures to: prevent the onset of disease, identify and
      treat asymptomatic persons who have already developed risk factors or preclinical
      disease, and restore function, minimize the negative effects of disease, and
      prevent disease-related complications. IMPLICATIONS FOR NURSING PRACTICE:
      Oncology nurses and advanced practice nurses are vital in the delivery of breast
      cancer prevention strategies.

PMID- 25951740
TI  - Molecular diagnostic testing in breast cancer.
AB  - OBJECTIVES: An overview of molecular tests used in the treatment of breast
      cancer, organized by stage and clinical condition. DATA SOURCES: Systematic
      review of scientific literature, guideline recommendations, and data published by
      test manufacturers. CONCLUSION: Several molecular tests that analyze expression
      of cancer-related genes have been validated in clinical trials and are
      recommended by clinical practice guidelines to inform diagnosis and treatment
      decisions for personalized interventions. IMPLICATIONS FOR NURSING PRACTICE:
      Molecular testing has become an important part of patient care for those with
      breast cancer. Oncology nurses must understand this methodology to prescribe
      tests, interpret the results, and provide guidance to patients.

PMID- 25951739
TI  - Genetic tests to identify risk for breast cancer.
AB  - OBJECTIVES: To describe the currently available genetic tests that identify
      hereditary risk for breast cancer. DATA SOURCES: Systematic review of scientific
      literature, clinical practice guidelines, and data published by test
      manufacturers. CONCLUSION: Changes in gene patent laws and advances in sequencing
      technologies have resulted in rapid expansion of genetic testing. While BRCA1/2
      are the most recognized genes linked to breast cancer, several laboratories now
      offer multi-gene panels to detect many risk-related mutations. IMPLICATIONS FOR
      NURSING PRACTICE: Genetic testing will be increasingly important in the
      prevention, diagnosis, and treatment of breast cancer. Oncology and advanced
      practice nurses must understand risk factors, significance of various genetic
      tests, and patient counseling.

PMID- 25951741
TI  - Local treatment of breast cancer.
AB  - OBJECTIVES: To describe the local control of breast cancer, including initial
      biopsy, lumpectomy or mastectomy, and sentinel node biopsy or axillary node
      dissection, and to discuss the role of radiation therapy following lumpectomy or
      mastectomy in advanced cancer. DATA SOURCES: PubMed, Scopus, Cochran. CONCLUSION:
      The local treatment of breast cancer is an essential component of primary breast
      cancer treatment. Residual cancer cells may increase the risk of recurrent
      ipsilateral disease. IMPLICATIONS FOR NURSING PRACTICE: Nurses and advanced
      practice nurses who provide care for cancer survivors should possess the skills
      to patiently teach information, empathetically understand the flagrant or
      suppressed emotional turmoil, explain the full complement of treatment options,
      appreciate the rationale behind choices made, and help patients navigate the
      educational and decisional byways.

PMID- 25951742
TI  - Reconstruction of the breast following mastectomy.
AB  - OBJECTIVES: To review immediate and delayed breast reconstructive options
      following surgery for high-risk or cancer-related unilateral or bilateral
      mastectomy and examine restorative interventions to promote a positive body image
      and long-term survivorship. DATA SOURCES: Review of PubMed, Scopus, and Cochran
      Review. CONCLUSION: For women facing mastectomy, a consultation with a
      plastic/reconstructive surgeon is a first step toward recovery with restoration
      of a missing body part. Nursing interventions are integral to physical and
      psychosocial healing. IMPLICATIONS FOR NURSING PRACTICE: An understanding of the
      reconstructive process can be beneficial in the care of women facing and
      recovering from a mastectomy. Psychological and physical issues occur whether the
      woman is undergoing bilateral prophylactic mastectomies for a high-risk condition
      or mastectomy as treatment for a malignant tumor.

PMID- 25951743
TI  - Endocrine therapy in breast cancer: the neoadjuvant, adjuvant, and metastatic
      approach.
AB  - OBJECTIVES: To review the rationale for endocrine therapy in the neoadjuvant,
      adjuvant, and metastatic breast cancer setting and to highlight clinical
      considerations unique to this treatment. DATA SOURCES: Contemporary literature,
      clinical guidelines, and national statistics. CONCLUSION: Endocrine therapy
      represents an important strategy in the management of both early and advanced
      hormone positive breast cancer. Additional research is required to better define
      the role of neoadjuvant therapy and the optimal duration of treatment.
      IMPLICATIONS FOR NURSING PRACTICE: Nurses play a pivotal role in the
      identification and management of endocrine therapy-associated symptoms. Prompt
      symptom intervention may improve therapy adherence and ultimately, may improve
      long-term disease outcomes.

PMID- 25951744
TI  - Systemic treatment for breast cancer: chemotherapy and biotherapy agents.
AB  - OBJECTIVES: To describe current systemic chemotherapy and biotherapy breast
      cancer treatments to better inform clinical nursing practice. DATA SOURCES:
      CINAHLl, Medline, Academic Research Periodicals, PubMed Clinical Queries,
      CANCERLIT, and EBM Reviews-Cochrane Central Register of Controlled Trials,
      Cochrane Database of Systematic Reviews (CDSR). CONCLUSION: Systemic therapeutic
      options for patients with breast cancer can be complex and varied. Furthermore,
      the guidelines for the treatment of breast cancer are frequently changing as new
      chemotherapies and biotherapies are being developed. IMPLICATIONS FOR NURSING
      PRACTICE: Nursing clinical practice has to remain current to accommodate new
      treatments and the side effect profiles. This knowledge is essential to providing
      evidence-based care for breast cancer patients receiving these treatments.

PMID- 25951745
TI  - Multimorbidity and breast cancer.
AB  - OBJECTIVES: To examine the significance of multimorbidity in breast cancer
      survivors, to explore multimorbidity in treatment decisions, and survivorship,
      and to consider multimorbidity assessment in clinical practice. DATA SOURCES:
      Literature review; clinical practice guidelines. CONCLUSION: Multimorbidity
      influences treatment decisions. Breast cancer survivors report greater
      multimorbidity compared with other cancer survivors. Multimorbidity increases
      with age; there may be racial and ethnic differences. Multimorbidity is
      associated with symptom burden, functional decline, low adherence to
      surveillance, and early retirement. IMPLICATIONS FOR NURSING PRACTICE: Clinical
      practice guidelines do not refer to multimorbidity and patient outcomes.
      Comprehensive geriatric assessment combined with survivorship care plan may be
      considered.

PMID- 25951747
TI  - The transition experience to breast cancer survivorship.
AB  - OBJECTIVES: To provide an overview of the concerns and needs of breast cancer
      survivors and describe approaches to quality patient-centered breast cancer
      survivorship care. DATA SOURCES: Review of the literature including research
      reports, review papers, and clinically based articles. CONCLUSION: Breast cancer
      survivors report unmet needs and desire information and support to manage
      symptoms, cope with uncertainty and fears of recurrence, and guidelines for
      healthy lifestyle behaviors. Individualized and tailored survivorship care is
      required to meet the needs of those with varied risk profiles and recovery
      patterns. IMPLICATIONS FOR NURSING PRACTICE: Nurses can be leaders in the
      assessment of needs after treatment, identification of those at higher risk for
      distress and ineffective coping, and in the delivery of high-quality care to
      breast cancer survivors.

PMID- 25951746
TI  - Health disparities across the breast cancer continuum.
AB  - OBJECTIVES: To provide a brief overview of disparities across the spectrum of
      breast cancer incidence, treatment, and long-term care during the survivorship
      period. DATA SOURCES: Review of the literature including research reports, review
      articles, and clinically based articles available through PubMed and CINAHL.
      CONCLUSION: Minority women generally experience worse breast cancer outcomes
      despite a lower incidence of breast cancer than whites. A variety of factors
      contribute to this disparity, including advanced stage at diagnosis, higher rates
      of aggressive breast cancer subtypes, and lower receipt of appropriate therapies
      including surgery, chemotherapy, and radiation. Disparities in breast cancer care
      also extend into the survivorship trajectory, including lower rates of endocrine
      therapy use among some minority groups, as well as differences in follow-up and
      survivorship care. IMPLICATIONS FOR NURSING PRACTICE: Breast cancer research
      should include improved minority representation and analyses by race, ethnicity,
      and socioeconomic status. While we cannot yet change the biology of this disease,
      we can encourage adherence to screening and treatment and help address the many
      physical, psychological, spiritual, and social issues minority women face in a
      culturally sensitive manner.

PMID- 25951748
TI  - Quantitative targeted absolute proteomics of rat blood-cerebrospinal fluid
      barrier transporters: comparison with a human specimen.
AB  - The purpose of this study was to determine absolute protein expression levels of
      transporters in rat choroid plexus, that is, the blood-cerebrospinal fluid
      barrier, and to compare them with the levels in the human choroid plexus. Plasma
      membrane fractions were prepared from pooled, freshly isolated choroid plexuses
      of 30 male Wistar rats and from frozen choroid plexus of one male human donor.
      Protein expression levels of 54 rat and 121 human molecules were measured, using
      a quantitative targeted absolute proteomics technique. In rat, oatp1a5 showed the
      most abundant protein expression (30.3 fmol/MUg protein), and its expression
      level was 3.1-, 4.5-, 5.5-, 8.4-, 9.0-, 9.9-, 22-, 91-, and 95-fold greater than
      those of glut1, oatp1c1, mrp1, mct1, oat3, pept2, mrp4, bcrp, and mdr1a,
      respectively. OATP1A2 (a possible homolog of rat oatp1a5), OATP1C1 and PEPT2 were
      not detected in human choroid plexus. MRP1, OAT3, and MRP4 showed 4.0-, 1.8-, and
      1.7-fold smaller expression levels in human than rat, respectively. MATE1 was
      detected in human, but not rat, and its expression level (8.61 fmol/MUg protein)
      was the highest among the xenobiotic transporters examined in human choroid
      plexus. These findings should be useful for understanding rat blood-cerebrospinal
      fluid barrier function and its differences from that in human. This is the first
      study clarifying the absolute protein expression levels of many transporters in
      the plasma membrane fractions of rat and human choroid plexuses, that is, blood
      cerebrospinal fluid barrier, by means of quantitative targeted absolute
      proteomics (QTAP) technique. This study also identified the protein expressions
      of some transporters including MATE1 and ABCA8 in the choroid plexus for the
      first time.

PMID- 25951749
TI  - A causal test of the motor theory of speech perception: a case of impaired speech
      production and spared speech perception.
AB  - The debate about the causal role of the motor system in speech perception has
      been reignited by demonstrations that motor processes are engaged during the
      processing of speech sounds. Here, we evaluate which aspects of auditory speech
      processing are affected, and which are not, in a stroke patient with dysfunction
      of the speech motor system. We found that the patient showed a normal phonemic
      categorical boundary when discriminating two non-words that differ by a minimal
      pair (e.g., ADA-AGA). However, using the same stimuli, the patient was unable to
      identify or label the non-word stimuli (using a button-press response). A control
      task showed that he could identify speech sounds by speaker gender, ruling out a
      general labelling impairment. These data suggest that while the motor system is
      not causally involved in perception of the speech signal, it may be used when
      other cues (e.g., meaning, context) are not available. 

PMID- 25951750
TI  - The role of cannabinoids in adult neurogenesis.
AB  - The processes underpinning post-developmental neurogenesis in the mammalian brain
      continue to be defined. Such processes involve the proliferation of neural stem
      cells and neural progenitor cells (NPCs), neuronal migration, differentiation and
      integration into a network of functional synapses within the brain. Both
      intrinsic (cell signalling cascades) and extrinsic (neurotrophins,
      neurotransmitters, cytokines, hormones) signalling molecules are intimately
      associated with adult neurogenesis and largely dictate the proliferative activity
      and differentiation capacity of neural cells. Cannabinoids are a unique class of
      chemical compounds incorporating plant-derived cannabinoids (the active
      components of Cannabis sativa), the endogenous cannabinoids and synthetic
      cannabinoid ligands, and these compounds are becoming increasingly recognized for
      their roles in neural developmental processes. Indeed, cannabinoids have clear
      modulatory roles in adult neurogenesis, probably through activation of both CB1
      and CB2 receptors. In recent years, a large body of literature has deciphered the
      signalling networks involved in cannabinoid-mediated regulation of neurogenesis.
      This timely review summarizes the evidence that the cannabinoid system is
      intricately associated with neuronal differentiation and maturation of NPCs and
      highlights intrinsic/extrinsic signalling mechanisms that are cannabinoid
      targets. Overall, these findings identify the central role of the cannabinoid
      system in adult neurogenesis in the hippocampus and the lateral ventricles and
      hence provide insight into the processes underlying post-developmental
      neurogenesis in the mammalian brain. 

PMID- 25951751
TI  - Hypofibrinogenemia induced by tigecycline: a potentially life-threatening
      coagulation disorder.
AB  - A 74-year-old female patient with end-stage renal disease, undergoing periodic
      hemodialysis, was hospitalized due to infection by multidrug-resistant
      Acinetobacter baumannii after hip replacement surgery. She was treated with
      tigecycline, a glycylcycline agent. Subsequently she developed coagulation
      disorders as substantiated by increased international normalized ratio (INR),
      prolonged partial thromboplastin time (aPTT), and severe hypofibrinogenemia,
      followed by transaminasemia, cholestasis, and anemia. Ultrasonography and
      computed tomography revealed no underlying pathological entities. Tigecycline was
      discontinued and the patient underwent daily hemodialysis and received multiple
      fresh frozen plasma transfusions. Additionally, she was treated with colistin.
      Her clinical and laboratory status improved. We suggest that patients treated
      with tigecycline should be monitored for changes in INR, aPTT, and fibrinogen
      levels to avoid severe, life-threatening coagulation disturbances. 

PMID- 25951753
TI  - Cation-pi and CH-pi Interactions in the Coordination and Solvation of
      Cu(+)(acetylene)n Complexes.
AB  - Copper-acetylene cation complexes of the form Cu(C2H2)n(+) (n = 1-8) are produced
      by laser ablation in a supersonic expansion of acetylene/argon. The ions are mass
      selected and studied via infrared laser photodissociation spectroscopy in the C-H
      stretching region (3000-3500 cm(-1)). The structure and bonding of these
      complexes are investigated through the number of infrared active bands, their
      relative intensities and their frequency positions. Density functional theory
      calculations are carried out in support of the experimental data. The combined
      data show that cation-pi complexes are formed for the n = 1-3 species, resulting
      in red-shifted C-H stretches on the acetylene ligands. The coordination of the
      copper cation is completed with three acetylene ligands, forming a "propeller"
      structure with D3 symmetry. Surprisingly, complexes with even greater numbers of
      acetylenes than this (4-6) have distinctive infrared band patterns quite
      different from those of the smaller complexes. Experiment combined with theory
      establishes that there is a fascinating pattern of second-sphere solvation
      involving the binding of acetylenes in bifurcated CH-pi binding sites at the apex
      of two core ligands. This binding motif leads to three equivalent sites for
      second-sphere ligands, which when filled form a highly symmetrical Cu(+)(C2H2)6
      complex. Solvent binding in this complex induces a structural change to planarity
      in the core, producing an appealing "core-shell" structure with D(3h) symmetry.

PMID- 25951754
TI  - Localized facial cold urticaria.

PMID- 25951752
TI  - Facial emotion recognition in childhood-onset bipolar I disorder: an evaluation
      of developmental differences between youths and adults.
AB  - OBJECTIVES: Bipolar disorder (BD) is a severe mental illness with high healthcare
      costs and poor outcomes. Increasing numbers of youths are diagnosed with BD, and
      many adults with BD report that their symptoms started in childhood, suggesting
      that BD can be a developmental disorder. Studies advancing our understanding of
      BD have shown alterations in facial emotion recognition both in children and
      adults with BD compared to healthy comparison (HC) participants, but none have
      evaluated the development of these deficits. To address this, we examined the
      effect of age on facial emotion recognition in a sample that included children
      and adults with confirmed childhood-onset type-I BD, with the adults having been
      diagnosed and followed since childhood by the Course and Outcome in Bipolar Youth
      study. METHODS: Using the Diagnostic Analysis of Non-Verbal Accuracy, we compared
      facial emotion recognition errors among participants with BD (n = 66; ages 7-26
      years) and HC participants (n = 87; ages 7-25 years). Complementary analyses
      investigated errors for child and adult faces. RESULTS: A significant diagnosis
      by-age interaction indicated that younger BD participants performed worse than
      expected relative to HC participants their own age. The deficits occurred both
      for child and adult faces and were particularly strong for angry child faces,
      which were most often mistaken as sad. Our results were not influenced by
      medications, comorbidities/substance use, or mood state/global functioning.
      CONCLUSIONS: Younger individuals with BD are worse than their peers at this
      important social skill. This deficit may be an important developmentally salient
      treatment target - that is, for cognitive remediation to improve BD youths'
      emotion recognition abilities.

PMID- 25951755
TI  - Blood pressure-lowering effect of the sodium glucose co-transporter-2 inhibitor
      ertugliflozin, assessed via ambulatory blood pressure monitoring in patients with
      type 2 diabetes and hypertension.
AB  - This study compared the blood pressure-lowering effect of ertugliflozin (1, 5, 25
      mg), hydrochlorothiazide (HCTZ; 12.5 mg) and placebo in 194 patients with type 2
      diabetes mellitus and hypertension for 4 weeks using ambulatory blood pressure
      monitoring. Endpoints (change from baseline to week 4) were: 24-h mean systolic
      blood pressure (SBP; primary); daytime, night-time, seated predose SBP, 24-h,
      daytime, night-time, seated predose diastolic blood pressure, 24-h urinary
      glucose excretion and fasting plasma glucose (FPG; secondary). Safety and
      tolerability were monitored. Significant decreases in placebo-corrected 24-h mean
      SBP (-3.0 to -4.0 mmHg) were recorded for all doses of ertugliflozin (for HCTZ,
      this was -3.2 mmHg). Daytime, but not night-time SBP was consistently reduced.
      Ertugliflozin produced dose-dependent significant decreases in FPG and increases
      in urinary glucose excretion. No notable changes in plasma renin activity or
      urinary aldosterone were seen. The most common adverse events were urinary tract
      infection, genital fungal infection, upper respiratory tract infection and
      musculoskeletal pain. 

PMID- 25951756
TI  - Towards the quantitative evaluation of visual attention models.
AB  - Scores of visual attention models have been developed over the past several
      decades of research. Differences in implementation, assumptions, and evaluations
      have made comparison of these models very difficult. Taxonomies have been
      constructed in an attempt at the organization and classification of models, but
      are not sufficient at quantifying which classes of models are most capable of
      explaining available data. At the same time, a multitude of physiological and
      behavioral findings have been published, measuring various aspects of human and
      non-human primate visual attention. All of these elements highlight the need to
      integrate the computational models with the data by (1) operationalizing the
      definitions of visual attention tasks and (2) designing benchmark datasets to
      measure success on specific tasks, under these definitions. In this paper, we
      provide some examples of operationalizing and benchmarking different visual
      attention tasks, along with the relevant design considerations. 

PMID- 25951757
TI  - Cardiovascular reactivity to mental stress and mortality in patients with heart
      failure.
AB  - OBJECTIVES: This study examined whether blood pressure (BP) and heart rate
      responses to acute mental stress were associated with mortality in patients with
      heart failure (HF). BACKGROUND: HF is characterized by reduced contractility and
      impaired BP reactivity. Compared to exercise-induced physiological changes, the
      effects of mental stress on BP and heart rate in HF are not well understood.
      METHODS: Patients with systolic HF (N = 100, 26% female, mean 65 +/- 12 years of
      age) underwent a structured public speech task, during which BP and heart rate
      were recorded. Stress-induced BP and heart rate reactivity were categorized as
      high (>75%), intermediate (25% to 75%), or low (<25%). Cox proportional hazards
      regressions were used to examine the predictive value of cardiovascular stress
      responses for mortality (median follow-up = 48.5 months), adjusting for age,
      implanted devices, and baseline BP and heart rate levels. RESULTS: At follow-up,
      31 patients had died (31%). Mortality rates were 2 times higher (hazard ratio
      [HR]: 2.04; 95% confidence interval [CI]: 1.15 to 3.60; p = 0.014) among patients
      with the lowest diastolic BP responses (mean = -2.4 +/- 5.4 mm Hg) to mental
      stress than among those patients with an intermediate diastolic BP response (mean
      = 7.3 +/- 2.5 mm Hg), adjusting for covariates. High diastolic BP reactivity
      (mean = 16.3 +/- 3.4 mm Hg) was not related to mortality (HR: 0.95; 95% CI: 0.55
      to 1.66). Systolic BP responses showed a similar but nonsignificant association.
      Multivariate analyses showed that a high heart rate response (>6.3 beats/min) to
      acute mental stress was associated with a reduced mortality risk (HR: 0.40; 95%
      CI: 0.16 to 1.00; p = 0.051) compared to patients with intermediate responses.
      CONCLUSIONS: Low diastolic BP reactivity to mental stress is independently
      associated with all-cause mortality in patients with HF. Larger studies need to
      replicate this finding and examine the role of psychosocial variables.

PMID- 25951758
TI  - The autonomic nervous system and cardiovascular health and disease: a complex
      balancing act.

PMID- 25951759
TI  - Assessing the use of international classification of diseases-10th revision codes
      from the emergency department for the identification of acute heart failure.
AB  - OBJECTIVES: The objective of this study was to compare administrative codes with
      chart review for patients with acute heart failure (AHF). BACKGROUND:
      Administrative databases are used in population health research; however, the
      validity of codes in the emergency department (ED) for AHF compared with chart
      review is uncertain. METHODS: A cohort of 952 patients with suspected AHF were
      prospectively recruited from 4 EDs in Edmonton, Alberta, Canada, from 2009 to
      2012. Patients had their diagnoses adjudicated by expert physicians using a
      standardized scoring system and detailed chart review. ED and hospital discharge
      International Classification of Diseases-10th Revision (ICD-10) codes were
      captured in the main diagnosis or in any diagnostic field. RESULTS: The 897
      patients had a median age of 77 years (interquartile range: 67 to 85 years), and
      806 (90%) were admitted to the hospital. Overall, 809 patients (90.2%) had AHF by
      adjudication and 660 (73.6%) had ICD-10 code I50.x as a main diagnosis in the ED
      administrative data, respectively. The positive predictive value of an AHF main
      diagnosis in the ED administrative data was 93.3% (95% confidence interval [CI]:
      92.0% to 94.7%), with sensitivity of 76.1% (95% CI: 75.0% to 77.2%) and
      specificity of 50.0% (95% CI: 39.8% to 60.1%). The positive predictive value for
      AHF in any diagnostic field of the ED administrative data was 92.0% (95% CI:
      91.1% to 93.0%), with a sensitivity of 89.4% (95% CI: 88.5% to 90.4%) and
      specificity of 28.4% (95% CI: 20.1% to 37.9%). CONCLUSIONS: An ICD-10 I50.x
      diagnosis in the ED is highly predictive of AHF compared with chart-level
      adjudication using a validated score. Thus, the use of these codes in ED
      administrative databases could identify AHF for clinical and epidemiological
      studies.

PMID- 25951760
TI  - Assessing the accuracy of emergency department international classification of
      diseases coding.

PMID- 25951761
TI  - Worsening Heart Failure Following Admission for Acute Heart Failure: A Pooled
      Analysis of the PROTECT and RELAX-AHF Studies.
AB  - OBJECTIVES: These studies conducted analyses to examine patient characteristics
      and outcomes associated with worsening heart failure (WHF). BACKGROUND: WHF
      during an admission for acute heart failure (AHF) represents treatment failure
      and is a potential therapeutic target for clinical trials of AHF. METHODS:
      Individual patient data from the PROTECT (Placebo-Controlled Randomized Study of
      the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients
      Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess
      Treatment Effect on Congestion and Renal Function) and RELAX-AHF (Relaxin in
      Acute Heart Failure) phase II and III studies were pooled for analysis. RESULTS:
      Of 3,691 patients, death or WHF through day 5 occurred in 12.4%, ranging from
      9.5% to 14.5% among studies. A multivariable model provided modest discrimination
      between patients who did or did not develop WHF (C-index = 0.68). After
      multivariable adjustment, WHF was associated with a mean increase in length of
      stay of 5.2 days (95% confidence interval [CI]: 4.6 to 5.8 days) and increased
      risks of 60-day HF or renal failure readmission or cardiovascular death (hazard
      ratio [HR]: 1.64, 95% CI: 1.34 to 2.01) and 180-day mortality (HR: 1.93, 95% CI:
      1.55 to 2.41) (all p < 0.001). The risk of mortality was higher in patients whose
      WHF required intravenous inotropes or mechanical therapy (HR: 3.03, 95% CI: 2.11
      to 4.36) compared with patients whose WHF was treated with intravenous loop
      diuretic alone (HR: 1.80, 95% CI: 1.36 to 2.36) (both p < 0.001). WHF was
      associated with larger increases in markers of renal and hepatic dysfunction
      during the first days of admission, but remained significantly associated with
      adverse outcomes after adjustment for these changes. CONCLUSIONS: WHF during the
      first 5 days of admission for AHF occurred in approximately 10% to 15% of
      patients and was associated with longer length of stay and higher risk for
      readmission and death.

PMID- 25951762
TI  - Worsening heart failure: challenges as a therapeutic target.

PMID- 25951763
TI  - Medical editors' grand rounds: a discussion of timely topics and editorial
      emergencies.

PMID- 25951764
TI  - Characterization of pulmonary hypertension in heart failure using the diastolic
      pressure gradient: the conundrum of high and low diastolic pulmonary gradient.

PMID- 25951765
TI  - Measurement to predict survival: the case of diastolic pulmonary gradient.

PMID- 25951766
TI  - Reply: characterization of pulmonary hypertension in heart failure using the
      diastolic pressure gradient: the conundrum of high and low diastolic pulmonary
      gradient.

PMID- 25951768
TI  - They stole her teeth! An exploration of adults with developmental disability
      experiences with dental care.
AB  - PURPOSE: The aim of this paper was to explore the experiences of adults with
      developmental disabilities (AWDD) in accessing and utilizing dental services in
      Vancouver, BC. METHODS: Participants were either self-advocates or
      parents/caregivers who discussed their experiences in five focus group
      discussions with 20 participants in total (age range 17-60 years, 2 males). Each
      focus group lasted on average 40 minutes. Transcripts were coded for thematic
      analysis; the codes were organized into themes and finally into domains. RESULTS:
      Seven domains relating to the participants' experiences with dental care were
      identified, and included communication, trust, and respect as provided-based
      domains to the quality of the dental experience for AWDD and their parents, while
      financial issues, transitional services, and waiting times were system-based
      barriers to access to dental care for theses AWDD. Finally, what makes for a
      positive dental experience was shared in terms of acknowledging parent's role as
      advocates and making simple accommodations to see AWDD by the dental office.
      CONCLUSIONS: Access to a care provider did not necessarily equate to satisfaction
      with quality of experience. Efforts have to focus on establishing communication
      and trust with AWDD patients as key to a positive dental experience. We encourage
      a global discussion on the need to better incorporate dental care for special
      needs individuals within dental school curricula.

PMID- 25951767
TI  - Aberrant mRNA splicing of paired box 4 (PAX4) IVS7-1G>A mutation causing maturity
      onset diabetes of the young, type 9.
AB  - AIMS: Paired box 4 (PAX4) mutations cause maturity-onset diabetes of the young,
      type 9 (MODY9). The molecular defect and alteration of PAX4 function associated
      with the mutation PAX4 IVS7-1G>A in a family with MODY9 and severe diabetic
      complications were studied. METHODS: We investigated the functional consequences
      of PAX4 IVS7-1G>A on mRNA splicing using minigene assays. Wild-type and mutant
      PAX4 were expressed in mouse pancreatic beta- and alpha-cell lines, and protein
      levels and translocation of PAX4 into the nucleus were determined. We also
      examined transcriptional repression of PAX4 target-gene promoters and beta-cell
      viability under diabetic-like (high-glucose) conditions. RESULTS: PAX4 IVS7-1G>A
      disrupts an acceptor splice site, causing an adjacent cryptic splice site within
      exon 8 to be used, resulting in a three-nucleotide deletion and glutamine
      deletion at position 250 (p.Q250del). Wild-type and PAX4 Q250del proteins were
      expressed at similar levels and could translocate normally into the nucleus in
      betaTC3 and alphaTC1.9 cells. However, the repressor functions of PAX4 Q250del on
      human insulin and glucagon promoters in INS-1 832/13 and alphaTC1.9 cells were
      significantly decreased, compared with that of wild-type PAX4. Moreover, the rate
      of apoptosis was increased in INS-1 cells over-expressing PAX4 Q250del when
      cultured in high-glucose conditions. CONCLUSIONS: PAX4 IVS7-1G>A caused aberrant
      mRNA splicing and PAX4 Q250 deletion. The mutation impaired PAX4 repressor
      functions on target-gene promoters and increased susceptibility to apoptosis upon
      high glucose exposure. Thus, PAX4 IVS7-1G>A contributes to the pathogenesis of
      diabetes in this MODY9 family through beta-cell dysfunction.

PMID- 25951769
TI  - The "peripheral washout sign" in focal hepatic lesions: not always an MRI sign of
      malignancy.
AB  - The "peripheral washout sign" is a magnetic resonance imaging finding defined as
      an enhancing liver lesion with a peripheral rim of de-enhancement relative to its
      center and surrounding parenchyma on delayed contrast-enhanced images. The
      "peripheral washout sign" has been described solely in malignant liver lesions.
      We present a histologically proven benign hepatic angiomyolipoma showing the
      "peripheral washout sign". To the best of our knowledge, this is the first report
      on a benign hepatic lesion exhibiting this extremely specific imaging feature. 

PMID- 25951770
TI  - Methods for mapping and categorization of DNA sequence reads from allopolyploid
      organisms.
AB  - Genome read categorization determines the genome of origin for sequence reads
      from an allopolyploid organism. Different techniques have been used to perform
      read categorization, mostly based on homoeo-SNPs identified between extant
      diploid relatives of allopolyploids. We present a novel technique for read
      categorization implemented by the software PolyDog. We demonstrate its accuracy
      and improved categorization relative to other methods. We discuss the situations
      in which one method or another might be most appropriate. 

PMID- 25951771
TI  - Localization of IGF proteins in various stages of ovarian follicular development
      and modulatory role of IGF-I on granulosa cell steroid production in water
      buffalo (Bubalus bubalis).
AB  - The present study aimed to determine the expression of insulin like growth factor
      (IGF) genes in the bubaline ovarian follicles and modulatory role of IGF-I on
      progesterone production from granulosa cells (GC) of pre-ovulatory follicle in
      vitro. According to size, follicles were classified into four groups: GI (small),
      GII (medium), GIII (large) and GIV (preovulatory). All IGF genes were expressed
      in both GC and theca interna (TI) cells. The relative expression of IGF-I and IGF
      receptor I (IGFR-I) genes increased with follicle size and was greatest in the
      pre-ovulatory follicle (P<0.05). Expression of IGF-II and IGFR-II genes was
      minimal in GC but was readily detected in TI cells. In TI cells, the gene
      expression was greater in medium and large as compared to small and pre-ovulatory
      follicles. The expression of all binding protein (IGFBP) genes was detected in
      both GC and TI cells. Expression of IGFBP-3 gene increased with follicle size and
      was greatest in pre-ovulatory follicles (P<0.05). The expression of IGFBP-2 and
      IGFBP-4 was less in pre-ovulatory follicles but expression of IGFBP-5 and IGFBP-6
      genes were greater at this stage. The GC culture was conducted for three time
      durations and with three doses of IGF-I. Expression of steroidogenic genes (StAR,
      CYP11A1, HSD3B) and progesterone concentration were increased in a dose and time
      dependent fashion. The present study, therefore, provided evidence of an
      autocrine/paracrine role of IGFs in follicular development and a stimulatory role
      of IGF1 in steroid production in GC of preovulatory follicles in the bubaline
      species. 

PMID- 25951772
TI  - Urban and Rural Differences in Parental Attitudes About Influenza Vaccination and
      Vaccine Delivery Models.
AB  - OBJECTIVES: To assess and compare among parents of healthy children in urban and
      rural areas: (1) reported influenza vaccination status; (2) attitudes regarding
      influenza vaccination; and (3) attitudes about collaborative models for influenza
      vaccination delivery involving practices and public health departments. METHODS:
      A mail survey to random samples of parents from 2 urban and 2 rural private
      practices in Colorado from April 2012 to June 2012. RESULTS: The response rate
      was 58% (288/500). In the prior season, 63% of urban and 41% of rural parents
      reported their child received influenza vaccination (P < .001). No differences in
      attitudes about influenza infection or vaccination between urban and rural
      parents were found, with 75% of urban and 73% of rural parents agreeing their
      child should receive an influenza vaccine every year (P = .71). High proportions
      reported willingness to participate in a collaborative clinic in a community
      setting (59% urban, 70% rural, P = .05) or at their child's provider (73% urban,
      73% rural, P = .99) with public health department assisting. Fewer (36% urban,
      53% rural, P < .01) were likely to go to the public health department if referred
      by their provider. Rural parents were more willing for their child to receive
      vaccination outside of their provider's office (70% vs. 55%, P = .01).
      CONCLUSIONS: While attitudes regarding influenza vaccination were similar, rural
      children were much less likely to have received vaccination. Most parents were
      amenable to collaborative models of influenza vaccination delivery, but rural
      parents were more comfortable with influenza vaccination outside their provider's
      office, suggesting that other venues for influenza vaccination in rural settings
      should be promoted.

PMID- 25951773
TI  - Simultaneous juvenile polyposis syndrome and neurofibromatosis type 1.

PMID- 25951774
TI  - Growth Directions of Precipitates in the Al-Si-Mg-Hf Alloy Using Combined EBSD
      and FIB 3D-Reconstruction Techniques.
AB  - Nanobelt-like precipitates in an Al-Si-Mg-Hf alloy were studied using electron
      backscattered diffraction (EBSD) and focused ion beam (FIB) scanning electron
      microscopy techniques. One grain of the Al matrix with a near [111] normal
      direction was identified by EBSD and the three-dimensional (3D) microstructure of
      nanobelt-like precipitates in this grain was studied using 3D-FIB. Ten growth
      directions of the nanobelt-like precipitates in the grain were identified. 

PMID- 25951775
TI  - Application of vacuum sealing drainage to the treatment of seawater-immersed
      blast-injury wounds.
AB  - The aims of this study were to observe the effects of vacuum sealing drainage
      (VSD) with three different negative pressures on the wound healing rate,
      macrophage count and the expression of hyaluronic acid (HA) as well as its
      receptor CD44 in seawater-immersed blast-injury wounds (SIBIW) and to determine
      the optimal negative pressure value. In a minipig SIBIW model, different suction
      pressures and routine dressing were applied. Histological and immunohistochemical
      comparisons as well as molecular biology methods were performed to compare the
      wound healing conditions, macrophage count and the levels of HA and CD44. The
      wound healing rate of the VSD group was significantly higher than that of the
      control group, with the -120 mmHg group exhibiting the best effects. The
      macrophage count of the VSD group was higher than that of the control group. The
      HA level fluctuation was higher in the VSD group, with the -120 mmHg and the -180
      mmHg groups showing the most significant fluctuation (P < 0.05). CD44 was
      expressed in the full-thickness wound-limbic tissues and was higher in the
      treatment group than that in the control group, with the -120 mmHg group having
      the most obvious expression. VSD significantly improved the healing ability and
      increased the macrophage count and the HA content. It also promoted CD44
      expression. -120 mmHg is the optimal negative pressure value.

PMID- 25951776
TI  - A Verbal Illusion: Now in Three Languages.
AB  - The so-called depth charge sentences (e.g., no head injury is too trivial to be
      ignored) were investigated in a comprehension experiment measuring both whether
      participants understood the stimuli and how certain they were of their
      interpretation. The experiment revealed that three factors influence the
      difficulty of depth charge type sentences: the number of negations, the
      plausibility of the relation between the subject and the verb, and finally the
      logic of the relation between the adjective and the verb. When a sentence is
      maximally complex (i.e., when there are multiple negations, the relation between
      subject and verb is implausible, and the relation between adjective and verb is
      illogical) participants misunderstood the sentence, but were at the same time
      certain of their answers. The experiment supports the idea that depth charge
      sentences create a verbal illusion-the sentences mean one thing, but people
      systematically understand them to mean the opposite. 

PMID- 25951777
TI  - Biotransformation of Steroids and Flavonoids by Cultures of Aspergillus niger.
AB  - Steroids are derivatives of the triterpenoid squalene, containing three fused
      cyclohexane rings and a cyclopentane ring, and flavonoids are derivatives of L
      phenylalanine, containing two aromatic rings joined by a three-carbon bridge that
      may form part of a heterocyclic ring. A great variety of steroids and flavonoids
      are produced by plants, and many additional steroids are produced by animals or
      fungi. Because these compounds have many nutritional and pharmaceutical values,
      and many of them cannot be produced by chemical synthesis, biotechnological
      processes are being developed that use cultures of Aspergillus niger and other
      fungi to transform steroids and flavonoids to a variety of metabolites. These
      biochemical reactions, including hydroxylation, dehydrogenation, O-methylation,
      demethylation, cleavage of rings, epoxide hydrolysis, double bond reduction, and
      others, may be used for the production of higher-value compounds. 

PMID- 25951778
TI  - Stimulatory Agents Simultaneously Improving the Production and Antioxidant
      Activity of Polyphenols from Inonotus obliquus by Submerged Fermentation.
AB  - Polyphenols are important secondary metabolites from the edible and medicinal
      mushroom Inonotus obliquus. Both the rarity of I. obliquus fruit body and the low
      efficiency of current method of submerged fermentation lead to a low yield of
      polyphenols. This study was aimed to determine the effect of applying stimulatory
      agents to liquid cultured I. obliquus on the simultaneous accumulation of exo
      polyphenols (EPC) and endo-polyphenols (IPC). Linoleic acid was the most
      effective out of the 17 tested stimulatory agents, the majority of which
      increased the EPC and IPC production. The result was totally different from the
      stimulatory effect of Tween 80 for polysaccharide production in previous studies.
      The addition of 1.0 g/L linoleic acid on day 0 resulted in 7-, 14-, and 10-fold
      of increase (p < 0.05) in the production of EPC extracted by ethyl acetate (EA
      EPC), EPC extracted by n-butyl alcohol (NB-EPC), and IPC, and significantly
      increased the production of ferulic acid, gallic acid, epicatechin-3-gallate
      (ECG), epigallocatechin-3-gallate (EGCG), phelligridin G, inoscavin B, and
      davallialactone. The EA-EPC, BA-EPC, and IPC from the linoleic acid-containing
      medium had significantly (p < 0.05) stronger scavenging activity against 2,2
      diphenyl-1-picrylhydrazyl radicals (DPPH), which was attributed to the higher
      content of these bioactive polyphenols.

PMID- 25951779
TI  - Influence of Feeding and Controlled Dissolved Oxygen Level on the Production of
      Poly(3-Hydroxybutyrate-co-3-Hydroxyvalerate) Copolymer by Cupriavidus sp. USMAA2
      4 and Its Characterization.
AB  - Copolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] has been
      the center of attention in the bio-industrial fields, as it possesses superior
      mechanical properties compared to poly(3-hydroxybutyrate) [P(3HB)]. The usage of
      oleic acid and 1-pentanol was exploited as the carbon source for the production
      of P(3HB-co-3HV) copolymer by using a locally isolated strain Cupriavidus sp.
      USMAA2-4. In this study, the productivity of polyhydroxyalkanoate (PHA) was
      improved by varying the frequency of feeding in fed-batch culture. The highest
      productivity (0.48 g/L/h) that represents 200 % increment was obtained by feeding
      the carbon source and nitrogen source three times and also by considering the
      oxygen uptake rate (OUR) and oxygen transfer rate (OTR). A significantly higher
      P(3HB-co-3HV) concentration of 25.7 g/L and PHA content of 66 wt% were obtained.
      The 3-hydroxyvalerate (3HV) monomer composition obtained was 24 mol% with the
      growth of 13.3 g/L. The different frequency of feeding carried out has produced a
      blend copolymer and has broadened the monomer distribution. In addition, increase
      in number of granules was also observed as the frequency of feeding increases. In
      general, the most glaring increment in productivity offer advantage for
      industrial P(3HB-co-3HV) production, and it is crucial in developing cost
      effective processes for commercialization.

PMID- 25951780
TI  - A Comprehensive Study on Chlorella pyrenoidosa for Phenol Degradation and its
      Potential Applicability as Biodiesel Feedstock and Animal Feed.
AB  - The present work evaluates the phenol degradative performance of microalgae
      Chlorella pyrenoidosa. High-performance liquid chromatography (HPLC) analysis
      showed that C. pyrenoidosa degrades phenol completely up to 200 mg/l. It could
      also metabolize phenol in refinery wastewater. Biokinetic parameters obtained are
      the following: growth kinetics, MU max (media) > MU max (refinery wastewater), K
      s(media) < K s(refinery wastewater), K I(media) > K I(refinery wastewater);
      degradation kinetics, q max (media) > q max (refinery wastewater), K s(media) < K
      s(refinery wastewater), K I(media) > K I(refinery wastewater). The microalgae
      could cometabolize the alkane components present in refinery wastewater. Fourier
      transform infrared (FTIR) fingerprinting of biomass indicates intercellular
      phenol uptake and breakdown into its intermediates. Phenol was metabolized as an
      organic carbon source leading to higher specific growth rate of biomass. Phenol
      degradation pathway was elucidated using HPLC, liquid chromatography-mass
      spectrometry (LC-MS) and ultraviolet-visible (UV-visible) spectrophotometry. It
      involved both ortho- and meta-pathway with prominence of ortho-pathway. SEM
      analysis shows that cell membrane gets wrinkled on phenol exposure. Phenol
      degradation was growth and photodependent. Infrared analysis shows increased
      intracellular accumulation of neutral lipids opening possibility for utilization
      of spent biomass as biodiesel feedstock. The biomass after lipid extraction could
      be used as protein supplement in animal feed owing to enhanced protein content.
      The phenol remediation ability coupled with potential applicability of the spent
      biomass as biofuel feedstock and animal feed makes it a potential candidate for
      an environmentally sustainable process.

PMID- 25951781
TI  - Theileria-transformed bovine leukocytes have cancer hallmarks.
AB  - The genus Theileria includes tick-transmitted apicomplexan parasites of ruminants
      with substantial economic impact in endemic countries. Some species, including
      Theileria parva and Theileria annulata, infect leukocytes where they induce
      phenotypes that are shared with some cancers, most notably immortalization,
      hyperproliferation, and dissemination. Despite considerable research into the
      affected host signaling pathways, the parasite proteins directly responsible for
      these host phenotypes remain unknown. In this review we outline current knowledge
      on the manipulation of host cells by transformation-inducing Theileria, and we
      propose that comparisons between cancer biology and host-Theileria interactions
      can reveal chemotherapeutic targets against Theileria-induced pathogenesis based
      on cancer treatment approaches. 

PMID- 25951782
TI  - The persistent influence of pediatric concussion on attention and cognitive
      control during flanker performance.
AB  - This study investigated the influence of concussion history on children's
      neurocognitive processing. Thirty-two children ages 8-10 years (16 with a
      concussion history, 16 controls) completed compatible and incompatible conditions
      of a flanker task while behavioral and neuroelectric data were collected.
      Relative to controls, children with a concussion history exhibited alterations in
      the sequential congruency effect, committed more omission errors, and exhibited
      decreased post-error accuracy. Children with a concussion history exhibited
      longer N2 latency across task conditions, increased N2 amplitude during the
      incompatible condition of the task, and decreased P3b amplitude across task
      conditions. Children with a history of concussion also exhibited decreased ERN
      and Pe amplitudes, with group difference increasing for the incompatible
      condition of the task. The current results indicate that pediatric concussion may
      lead to subtle, but pervasive deficits in attention and cognitive control. These
      results serve to inform a poorly understood but significant public health
      concern. 

PMID- 25951783
TI  - Deficit in late-stage contingent negative variation provides evidence for
      disrupted movement preparation in patients with conversion paresis.
AB  - Conversion paresis is the presence of unexplained weakness without detectable
      neuropathology that is not feigned. To examine the 'abnormal preparation' and
      'disrupted execution' hypotheses proposed to explain the movement deficits in
      conversion paresis, electroencephalographic, electromyographic and kinematic
      measures were recorded during motor preparation and execution. Six patients with
      unilateral upper limb conversion weakness, 24 participants feigning weakness and
      12 control participants performed a 2-choice precued reaction time task. Precues
      provided advance information about the responding hand or finger. Patients and
      feigners demonstrated similar diminished force, longer movement time and extended
      duration of muscle activity in their symptomatic limb. Patients showed
      significantly suppressed contingent negative variation (CNV) amplitudes, but only
      when the symptomatic limb was precued. Despite the similarity in performance
      measures, this CNV suppression was not seen in feigners. Diminished CNV for
      symptomatic hand precues may reflect engagement of an inhibitory mechanism
      suppressing cortical activity related to preparatory processes. 

PMID- 25951784
TI  - Headaches and sleep disorders.
AB  - Headaches and sleep disorders are associated in a complex manner. Both the
      disorders are common in the general population, but the relationship between the
      two is more than coincidental. Sleep disorders can exacerbate headache sand the
      converse is also true. Treatment of sleep disorders can have a positive impact on
      the treatment of headaches. Screening for sleep disorders should be considered in
      all patients with headaches. This can be accomplished with brief screening tools.
      Those who screen positively can be further evaluated or referred to asleep
      specialist.

PMID- 25951785
TI  - Satisfaction of health professionals after implementation of a primary care
      hospital emergency centre in Switzerland: A prospective before-after study.
AB  - BACKGROUND AND AIM: The increasing number of patients requiring emergency care is
      a challenge and leads to decreased satisfaction of health professionals at
      emergency departments (EDs). Thus, a Swiss hospital implemented a hospital
      associated primary care centre at the ED. The study aim was to investigate
      changes in job satisfaction of ED staff before and after the implementation of
      this new service model and to measure hospital GPs' (HGPs) satisfaction at the
      hospital-associated primary care centre. METHOD: This study was embedded in a
      large prospective before-after study over two years. We examined changes in job
      satisfaction with a questionnaire followed by selected interviews approaching all
      of the involved 25 ED staff members and 38 HGPs. RESULTS: The new emergency care
      model increased job satisfaction of ED staff and HGPs in all measured dimensions.
      The overall job satisfaction of ED employees improved from 76.5 to 83.9 points
      (visual analogue scale 0-100; difference 7.4 points [95% CI: 1.3 to 13.5, p =
      0.02]). 86% of 29 HGPs preferred to provide their out-of-hours service at the new
      hospital-associated primary care centre. CONCLUSIONS: The hospital-associated
      primary care centre is a promising option to improve job satisfaction of
      different health professionals in emergency care.

PMID- 25951787
TI  - R2R-printed inverted OPV modules--towards arbitrary patterned designs.
AB  - We describe the fabrication of roll-to-roll (R2R) printed organic photovoltaic
      (OPV) modules using gravure printing and rotary screen-printing processes. These
      two-dimensional printing techniques are differentiating factors from coated OPVs
      enabling the direct patterning of arbitrarily shaped and sized features into
      visual shapes and, increasing the freedom to connect the cells in modules. The
      inverted OPV structures comprise five layers that are either printed or patterned
      in an R2R printing process. We examined the rheological properties of the inks
      used and their relationship with the printability, the compatibility between the
      processed inks, and the morphology of the R2R-printed layers. We also evaluate
      the dimensional accuracy of the printed pattern, which is an important
      consideration in designing arbitrarily-shaped OPV structures. The photoactive
      layer and top electrode exhibited excellent cross-dimensional accuracy
      corresponding to the designed width. The transparent electron transport layer
      extended 300 um beyond the designed values, whereas the hole transport layer
      shrank 100 um. We also examined the repeatability of the R2R fabrication process
      when the active area of the module varied from 32.2 cm(2) to 96.5 cm(2). A
      thorough layer-by-layer optimization of the R2R printing processes resulted in
      realization of R2R-printed 96.5 cm(2) sized modules with a maximum power
      conversion efficiency of 2.1% (mean 1.8%) processed with high functionality. 

PMID- 25951786
TI  - Studying non-covalent drug-DNA interactions.
AB  - Drug-DNA interactions have been extensively studied in the recent past. Various
      techniques have been employed to decipher these interactions. DNA is a major
      target for a wide range of drugs that may specifically or non-specifically
      interact with DNA and affect its functions. Interaction between small molecules
      and DNA are of two types, covalent interactions and non-covalent interactions.
      Three major modes of non-covalent interactions are electrostatic interactions,
      groove binding and intercalative binding. This review primarily focuses on
      discussing various techniques used to study non-covalent interactions that occur
      between drugs and DNA. Additionally, we report several techniques that may be
      employed to analyse the binding mode of a drug with DNA. These techniques provide
      data that are reliable and simple to interpret. 

PMID- 25951788
TI  - Characterization of severe hand, foot, and mouth disease in Shenzhen, China, 2009
      2013.
AB  - Hand, foot, and mouth disease (HFMD) is caused by human enteroviruses, especially
      by enterovirus 71 (EV71) and coxsackievirus A16 (CA16). Patients infected with
      different enteroviruses show varied clinical symptoms. The aim of this study was
      to determine whether the etiological spectrum of mild and severe HFMD changed,
      and the association between pathogens and clinical features. From 2009 to 2013, a
      total of 2,299 stool or rectal specimens were collected with corresponding
      patient data. A dynamic view of the etiological spectrum of mild and severe HFMD
      in Shenzhen city of China was provided. EV71 accounted for the majority
      proportion of severe HFMD cases and fatalities during 2009-2013. CA16 and EV71
      were gradually replaced by coxsackievirus A6 (CA6) as the most common serotype
      for mild HFMD since 2010. Myoclonic jerk and vomiting were the most frequent
      severe symptoms. Nervous system complications, including aseptic encephalitis and
      aseptic meningitis were observed mainly in patients infected by EV71. Among EV71,
      CA16, CA6, and CA10 infection, fever and pharyngalgia were more likely to
      develop, vesicles on the hand, foot, elbow, knee and buttock were less likely to
      develop in patients infected with CA10. Vesicles on the mouth more frequently
      occurred in the patients with CA6, but less in the patient with EV71.
      Associations between diverse enterovirus serotypes and various clinical features
      were discovered in the present study, which may offer further insight into early
      detection, diagnosis and treatment of HFMD.

PMID- 25951789
TI  - Automated isolation of primary antigen-specific T cells from donor lymphocyte
      concentrates: results of a feasibility exercise.
AB  - BACKGROUND: The safety and clinical efficacy of adoptive transfer of
      prospectively isolated antigen-specific T cells are well established. Several
      competing selection methods are available, one of which is based on
      immunomagnetic enrichment of T cells secreting IFNgamma after incubation with the
      relevant antigen. The proprietary, GMP-conforming selection technology, called
      'cytokine capture system' (CCS) is established in many laboratories for the
      CliniMACS Plus system. It is robust and efficient, but labour-intensive and
      incompatible with a single-shift working schedule. An automatic immunomagnetic
      cell processing system, CliniMACS Prodigy ('Prodigy'), including a protocol for
      fully automatic CCS execution was recently released. MATERIAL AND METHODS:
      Feasibility of clinical-scale CMV-specific T-cell selection using Prodigy was
      evaluated using leukoapheresis products from five healthy CMV sero-positive
      volunteers. Clinical reagents and consumables were used throughout. RESULTS: The
      process required no operator input beyond set-up and QC-sample collection, that
      is, feasibility was given. An IFNgamma-secreting target T-cell population was
      detectable after stimulation, and >2 log-scale relative depletion of not CMV
      reactive T cells in the target population was achieved. Purity, that is the
      frequency of CMV-reactive T cells among all CD3(+) cells ranged between 64 and
      93%. CONCLUSION: The CCS protocol on Prodigy is unrestrictedly functional. It
      runs fully automatically beyond set-up and thus markedly reduces labour. The
      quality of the products generated is similar to products generated with CliniMACS
      Plus. The automatic system is thus suitable for routine clinical application.

PMID- 25951790
TI  - Preoperative assessment and classification of benign laryngotracheal stenosis: a
      consensus paper of the European Laryngological Society.
AB  - Adult and pediatric laryngotracheal stenoses (LTS) comprise a wide array of
      various conditions that require precise preoperative assessment and
      classification to improve comparison of different therapeutic modalities in a
      matched series of patients. This consensus paper of the European Laryngological
      Society proposes a five-step endoscopic airway assessment and a standardized
      reporting system to better differentiate fresh, incipient from mature,
      cicatricial LTSs, simple one-level from complex multilevel LTSs and finally
      "healthy" from "severely morbid" patients. The proposed scoring system, which
      integrates all of these parameters, may be used to help define different groups
      of LTS patients, choose the best treatment modality for each individual patient
      and assess distinct post-treatment outcomes accordingly. 

PMID- 25951791
TI  - Psychological stress and its relationship with persistent allergic rhinitis.
AB  - Allergic rhinitis is considered to be a major health problem that impairs quality
      of life. A possible relationship with psychological stress may exist. The aim of
      this study is to verify the relationship between persistent allergic rhinitis
      (PAR) and psychological stress aiming to improve treatment and thereby quality of
      life (QOL) of patients. Patients with PAR (166) were diagnosed then analyzed
      using the Kessler Psychological Distress Scale. Patients with allergic rhinitis
      and who were positive on the Kessler scale (122) were randomly divided equally
      into a control group which received levocetirizine and a study group which
      received levocetirizine and imipramine. Nasal symptom assessment and QOL
      assessment were performed in all patients after treatment. Of the 166 patients
      with PAR, 122 (73.5 %) were positive on the Kessler Psychological Distress Scale.
      There was a marked improvement in the study group compared with the control group
      as regards nasal symptoms with better QOL in the study group (6.93) compared with
      the control group (2.13). Psychological stress has a strong impact on persistent
      allergic rhinitis. When stress is controlled by a combined treatment of
      imipramine and levocetirizine, allergic rhinitis symptoms improved and a better
      QOL was obtained. LEVEL OF EVIDENCE: 3b.

PMID- 25951792
TI  - Iterative reconstruction of detector response of an Anger gamma camera.
AB  - Statistical event reconstruction techniques can give better results for gamma
      cameras than the traditional centroid method. However, implementation of such
      techniques requires detailed knowledge of the photomultiplier tube light-response
      functions. Here we describe an iterative method which allows one to obtain the
      response functions from flood irradiation data without imposing strict
      requirements on the spatial uniformity of the event distribution. A successful
      application of the method for medical gamma cameras is demonstrated using both
      simulated and experimental data. An implementation of the iterative
      reconstruction technique capable of operating in real time is presented. We show
      that this technique can also be used for monitoring photomultiplier gain
      variations. 

PMID- 25951794
TI  - Small molecule binding to a G-hairpin and a G-triplex: a new insight into
      anticancer drug design targeting G-rich regions.
AB  - To gain new insights into G-quadruplex-drug interactions, we captured the
      solution-state structures of the complexes between a drug-like small molecule and
      a G-hairpin/G-triplex. Our results indicated that the ligand initially binds to
      the intermediates and induces stepwise folding into a quadruplex. 

PMID- 25951793
TI  - Presence of pathogenic enteric viruses in illegally imported meat and meat
      products to EU by international air travelers.
AB  - One hundred twenty two meat samples confiscated from passengers on flights from
      non-European countries at the International Airport of Bilbao (Spain) were tested
      for the presence of the main foodborne viral pathogens (human noroviruses
      genogroups I and II, hepatitis A and E viruses) during 2012 and 2013. A sample
      process control virus, murine norovirus, was used to evaluate the correct
      performance of the method. Overall, 67 samples were positive for at least one
      enteric viruses, 65 being positive for hepatitis E virus (53.3%), 3 for human
      norovirus genogroup I (2.5%) and 1 for human norovirus genogroup II (0.8%),
      whereas hepatitis A virus was not detected in any sample. The type of positive
      meat samples was diverse, but mainly was pork meat products (64.2%). The
      geographical origin of the positive samples was wide and diverse; samples from 15
      out 19 countries tested were positive for at least one virus. However, the
      estimated virus load was low, ranging from 55 to 9.0 * 10(4) PDU per gram of
      product. The results obtained showed the potential introduction of viral agents
      in travelers' luggage, which constitute a neglected route of introduction and
      transmission.

PMID- 25951795
TI  - Early cell response to contact with biomaterial's surface.
AB  - Most biomaterials at present have sufficient mechanical properties; however
      compliance with standards for biocompatibility is often not sufficient in
      clinical practice. This may be due to the complexity of biological systems in
      general and the diversity of individual responses to these materials by implant
      recipients. Significant improvement of biocompatibility must involve surface
      modification of implants, which in the future will make it possible to introduce
      individually selected types of surface modification for individual recipients.
      The key to this technology seems to be understanding the processes occurring at
      the site of contact of the implant with the tissue. Processes resulting from the
      stress generated by the contact of the biomaterial surfaces were observed with
      endothelial cells line EA.hy926, and it was demonstrated that differently
      modified surfaces of medical steel (polished medical steel and medical steel
      coated with Parylene C and nanocrystalline diamond) cause diverse cellular
      response in cells grown on these surfaces, on both the cellular (cell morphology
      and cell survival) and molecular (transcriptome and proteome profiles) levels.
      The herein presented observations are a good starting point not only for further
      research and the development of far-reaching personalization of medical implants,
      but also to study the potential use of cells as a specific sensor capable of
      recognizing different surfaces with which these cells come into contact. (c) 2015
      Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 880-893,
      2016.

PMID- 25951796
TI  - eQTL mapping identifies insertion- and deletion-specific eQTLs in multiple
      tissues.
AB  - Genome-wide gene expression quantitative trait loci (eQTL) mapping have been
      focused on single-nucleotide polymorphisms and have helped interpret findings
      from diseases mapping studies. The functional effect of structure variants,
      especially short insertions and deletions (indel) has not been well investigated.
      Here we impute 1,380,133 indels based on the latest 1,000 Genomes Project panel
      into three eQTL data sets from multiple tissues. Imputation of indels increased
      9.9% power and identifies indel-specific eQTLs for 325 genes. We find introns and
      vicinities of UTRs are more enriched of indel eQTLs and 3.6 (single-tissue)
      9.2%(multi-tissue) of previous identified eSNPs were taggers of eindels.
      Functional analyses identifies epigenetics marks, gene ontology categories and
      disease GWAS loci affected by SNPs and indels eQTLs showing tissue-consistent or
      tissue-specific effects. This study provides new insights into the underlying
      genetic architecture of gene expression across tissues and new resource to
      interpret function of diseases and traits associated structure variants. 

PMID- 25951798
TI  - The Evolution of Occupational Segregation in the United States, 1940-2010: Gains
      and Losses of Gender-Race/Ethnicity Groups.
AB  - The aim of this article is twofold: (1) to descriptively explore the evolution of
      occupational segregation of women and men of different racial/ethnic groups in
      the United States during 1940-2010, and (2) to assess the consequences of
      segregation for each group. For that purpose, in this article, we propose a
      simple index that measures the monetary loss or gain of a group derived from its
      overrepresentation in some occupations and underrepresentation in others. This
      index has a clear economic interpretation. It represents the per capita advantage
      (if the index is positive) or disadvantage (if the index is negative) of the
      group, derived from its segregation, as a proportion of the average wage of the
      economy. Our index is a helpful tool not only for academics but also for
      institutions concerned with inequalities among demographic groups because it
      makes it possible to rank them according to their segregational nature. 

PMID- 25951799
TI  - Does Schooling Affect Women's Desired Fertility? Evidence From Malawi, Uganda,
      and Ethiopia.
AB  - Demographic scholarship suggests that schooling plays an important role in
      transforming fertility preferences in the early stages of fertility decline.
      However, there is limited evidence on the relationship between schooling and
      fertility preferences that addresses the endogeneity of schooling. I use the
      implementation of Universal Primary Education (UPE) policies in Malawi, Uganda,
      and Ethiopia in the mid-1990s to conduct a fuzzy regression discontinuity
      analysis of the effect of schooling on women's desired fertility. Findings
      indicate that increased schooling reduced women's ideal family size and very high
      desired fertility across all three countries. Additional analyses of potential
      pathways through which schooling could have affected desired fertility suggest
      some pathways--such as increasing partner's education--were common across
      contexts, whereas other pathways were country-specific. This analysis contributes
      to demographic understandings of the factors influencing individual-level
      fertility behaviors and thus aggregate-level fertility decline in sub-Saharan
      Africa.

PMID- 25951800
TI  - The Effects of Gendered Social Capital on U.S. Migration: A Comparison of Four
      Latin American Countries.
AB  - This article contributes to understandings of gendered social capital by
      analyzing the effects of gendered ties on the migration of men and women from
      four Latin American countries (Mexico, Costa Rica, Nicaragua, and the Dominican
      Republic) to the United States. The research theorizes the importance of strong
      and weak ties to men and women in each sending country as a product of the gender
      equity gap in economic participation (low/high) and incidence of female-led
      families (low/high). The findings reveal that ties to men increase the odds of
      migration from countries where gender equity and incidence of female-led families
      are low, while ties to women are more important for migration from countries
      where gender equity and female-led families are high. Previous research on
      migration and social capital details the importance of network ties for providing
      resources and the role of gender in mediating social capital quality and access
      to network support. Results reveal that not only are different kinds of ties
      important to female and male migration, but migrants from different countries
      look to different sources of social capital for assistance. 

PMID- 25951797
TI  - Claudins: Gatekeepers of lung epithelial function.
AB  - The lung must maintain a proper barrier between airspaces and fluid filled
      tissues in order to maintain lung fluid balance. Central to maintaining lung
      fluid balance are epithelial cells which create a barrier to water and solutes.
      The barrier function of these cells is mainly provided by tight junction proteins
      known as claudins. Epithelial barrier function varies depending on the different
      needs within the segments of the respiratory tree. In the lower airways, fluid is
      required to maintain mucociliary clearance, whereas in the terminal alveolar
      airspaces a thin layer of surfactant enriched fluid lowers surface tension to
      prevent airspace collapse and is critical for gas exchange. As the epithelial
      cells within the segments of the respiratory tree differ, the composition of
      claudins found in these epithelial cells is also different. Among these
      differences is claudin-18 which is uniquely expressed by the alveolar epithelial
      cells. Other claudins, notably claudin-4 and claudin-7, are more ubiquitously
      expressed throughout the respiratory epithelium. Claudin-5 is expressed by both
      pulmonary epithelial and endothelial cells. Based on in vitro and in vivo model
      systems and histologic analysis of lungs from human patients, roles for specific
      claudins in maintaining barrier function and protecting the lung from the effects
      of acute injury and disease are being identified. One surprising finding is that
      claudin-18 and claudin-4 control lung cell phenotype and inflammation beyond
      simply maintaining a selective paracellular permeability barrier. This suggests
      claudins have more nuanced roles for the control of airway and alveolar
      physiology in the healthy and diseased lung. 

PMID- 25951801
TI  - Association between Helicobacter pylori and pancreatic cancer risk: a meta
      analysis.
AB  - PURPOSE: Gastric colonization with Helicobacter pylori (H. pylori) has been
      implicated in the pathogenesis of pancreatic cancer, but results of
      epidemiological studies have been inconclusive. We analyzed data from the
      Queensland Pancreatic Cancer Study, an Australian population-based case-control
      study, and incorporated our findings into an updated meta-analysis. METHODS:
      Blood samples were obtained from 580 patients and 626 controls, and enzyme-linked
      immunosorbent assay kits were used to determine seropositivity to H. pylori and
      its virulence protein, cytotoxin-associated gene A (CagA). Odds ratios (ORs) and
      95 % confidence intervals (CIs) were calculated using logistic regression.
      Results were incorporated into a meta-analysis along with results of studies
      identified through systematic literature review. Adjusted ORs and 95 % CIs were
      calculated using the DerSimonian and Laird random-effects model. RESULTS: No
      overall association was observed between H. pylori seropositivity and risk of
      pancreatic cancer (OR 1.00; 95 % CI 0.74-1.35). Nonsignificantly decreased
      pancreatic cancer risk was observed with CagA seropositivity (OR 0.74; 95 % CI
      0.48-1.15) and increased risk with CagA-negative H. pylori seropositivity (OR
      1.23; 95 % CI 0.83-1.82). Ten studies were included in the meta-analysis. There
      was no significant overall association between H. pylori seropositivity and
      pancreatic cancer risk (OR 1.13; 95 % CI 0.86-1.50), but evidence of CagA strain
      specific associations (OR 0.78; 95 % CI 0.67-0.91 and OR 1.30; 95 % CI 1.02-1.65
      for CagA-positive and CagA-negative strains, respectively). CONCLUSIONS: Our
      results provide further evidence for the existence of strain-specific
      associations between H. pylori and pancreatic cancer.

PMID- 25951802
TI  - Coencapsulation of hydrophobic and hydrophilic antituberculosis drugs in
      synergistic Brij 96 microemulsions: a biophysical characterization.
AB  - A microemulsion has been formulated to coencapsulate antituberculosis drugs to
      solve the issue of stability of rifampicin (RIF) in the presence of isoniazid
      (INH) and pyrazinamide (PZA). The structural transition, solubilization locus,
      and quantitative release of drugs without interference have been estimated.
      Derivative absorbance spectroscopy, especially ratio derivative and double
      divisor ratio derivative methods, has been employed for estimating the release.
      The coencapsulation of the anti-tuberculosis drugs were carried out in single,
      binary, or ternary mixtures and occupy the same solubilization sites in multiple
      drugs microemulsion systems as in the case of single drug-loaded systems. INH and
      PZA obey the diffusional (Fickian) release mechanism, whereas RIF shows anomalous
      release. Resazurin assay and agar well diffusion method were adopted for
      cytotoxicity analysis and antimicrobial activity, respectively. Cytotoxicity was
      found to be dependent on concentration and on colloidal structure of
      microemulsion.

PMID- 25951804
TI  - Dear colleagues and friends in the world of neuroradiology. Introduction.

PMID- 25951803
TI  - Outcomes of temporomandibular joint arthroscopy in patients with painful but
      otherwise normal joints.
AB  - The aim of this retrospective clinical study was to assess the clinical outcomes
      of temporomandibular joint (TMJ) arthroscopy in patients who presented with
      category 1 normal joints. The null hypothesis being tested was that patients with
      normal joints do not respond to TMJ arthroscopy. The clinical records of 116
      patients who had undergone TMJ arthroscopy by the author from 2010 to 2013 were
      retrieved and individually analysed for inclusion in this retrospective, cohort
      clinical study. The inclusion criteria used to select patients for this study
      were those who had arthroscopically proven category 1 normal joints, free of
      intra-articular pathology. Of the 14 patients who were found to have normal
      joints, only 10 could be contacted for a follow-up survey. Despite the fact that
      all patients were informed that no joint pathology was found, six out of the 10
      patients reported improvement in their temporomandibular disorder (TMD) symptoms
      that lasted for more than 6 months following TMJ arthroscopy. The results of this
      investigation indicate that we can reject the null hypothesis, and that patients
      with normal TMJs do indeed respond to TMJ arthroscopy. What this limited study
      has highlighted is the pervasive effects of the placebo that all surgeons need to
      keep in mind when formulating treatment plans for patients with TMD. 

PMID- 25951805
TI  - Urinary biomarkers of chronic allograft nephropathy.
AB  - PURPOSE: Chronic allograft nephropathy (CAN) is widely accepted as the leading
      cause of renal allograft loss after the first year post transplantation. This
      study aimed to identify urinary biomarkers that could predict CAN in transplant
      patients. EXPERIMENTAL DESIGN: The study included 34 renal transplant patients
      with histologically proven CAN and 36 renal transplant patients with normal renal
      function. OrbiTrap MS was utilized to analysis a urinary fraction in order to
      identify other members of a previously identified biomarker tree . This novel
      biomarker pattern offers the potential to distinguish between transplant
      recipients with CAN and those with normal renal function. RESULTS: The primary
      node of the biomarker pattern was reconfirmed as beta2 microglobulin. Three other
      members of this biomarker pattern were identified: neutrophil gelatinase
      associated lipocalin, clusterin, and kidney injury biomarker 1. Significantly
      higher urinary concentrations of these proteins were found in patients with CAN
      compared to those with normal kidney function. CONCLUSIONS AND CLINICAL
      RELEVANCE: While further validation in a larger more-diverse patient population
      is required to determine if this biomarker pattern provides a potential means of
      diagnosing CAN by noninvasive methods in a clinical setting, this study clearly
      demonstrates the biomarkers' ability to stratify patients based on transplant
      function.

PMID- 25951806
TI  - Comprehensive clinical approach to renal tubular acidosis.
AB  - Renal tubular acidosis (RTA) is essentially characterized by normal anion gap and
      hyperchloremic metabolic acidosis. It is important to understand that despite
      knowing the disease for 60-70 years, complexities in the laboratory tests and
      their interpretation still make clinicians cautious to diagnose and label types
      of tubular disorder. Hence, we are writing this mini-review to emphasize on the
      step wise approach to RTA with some understanding on its basic etiopathogenesis.
      This will definitely help to have an accurate interpretation of urine and blood
      reports in correlation with the clinical condition. RTA can be a primary or
      secondary defect and results either due to abnormality in bicarbonate ion
      absorption or hydrogen ion secretion. Primary defects are common in children due
      to gene mutation or idiopathic nature while secondary forms are more common in
      adults. We are focusing and explaining here in this review all the clinical and
      laboratory parameters which are essential for making the diagnosis of RTA and
      excluding the extrarenal causes of hyperchloremic, normal anion gap metabolic
      acidosis. 

PMID- 25951807
TI  - Increased risk of renal biopsy complications in patients with IgA-nephritis.
AB  - BACKGROUND: The aim of this study was to investigate if specific clinical and
      histological findings can be related to biopsy complications to enable more
      closely monitoring patients at high risk. METHODS: Results from 1081 biopsies
      (994 patients, median age 54.5 years; 896 native and 185 transplant kidney
      biopsies) were included. Diagnostic quality, morphology, clinical data and
      complications were prospectively registered. RESULTS: In native kidney biopsies,
      the most common diagnosis was IgA-nephritis, while in transplant kidney biopsies
      it was rejection. Patients with IgA-nephritis had a higher risk of major
      complications (11.7 versus 6.4 %, Odds Ratio (OR) 1.8, Confidence Interval (CI)
      1.1-3.2) when compared to patients with other diseases. In native kidney
      biopsies, patients who experienced major complications had higher degrees of
      glomerulosclerosis (31 versus 20 %, p = 0.008), whereas in transplant kidney
      biopsies, patients had higher degrees of interstitial fibrosis (82 versus 33 %, p
      < 0.001) when compared to patients without major complications. IgA-nephritis
      patients had a higher risk of re-biopsies (4.7 versus 1.3 %, OR 4, CI 1.5-11)
      than patients with other diseases. Patients with native kidneys who needed re
      biopsies were younger (42.6 versus 52.3 years, p = 0.031) and had a higher degree
      of interstitial fibrosis (63 versus 34 %, p = 0.046). CONCLUSIONS: Patients with
      IgA-nephritis have an increased risk of major biopsy complications. The risk of
      re-biopsies was higher in younger individuals and in patients with IgA-nephritis.

PMID- 25951808
TI  - Flexible supercapacitors based on paper substrates: a new paradigm for low-cost
      energy storage.
AB  - Paper-based supercapacitors (SCs), a novel and interesting group of flexible
      energy storage devices, are attracting more and more attention from both industry
      and academia. Cellulose papers with a unique porous bulk structure and rough and
      absorptive surface properties enable the construction of paper-based SCs with a
      reasonably good performance at a low price. The inexpensive and environmentally
      friendly nature of paper as well as simple fabrication techniques make paper
      based SCs promising candidates for the future 'green' and 'once-use-and-throw
      away' electronics. This review introduces the design, fabrication and
      applications of paper-based SCs, giving a comprehensive coverage of this
      interesting field. Challenges and future perspectives are also discussed. 

PMID- 25951809
TI  - 2,3,5-Trimethoxy-4-cresol, an anti-metastatic constituent from the solid-state
      cultured mycelium of Antrodia cinnamomea and its mechanism.
AB  - Antrodia cinnamomea is a valuable and unique edible fungus originating from the
      forests of Taiwan. In this study, an anti-metastatic compound, 2,3,5-trimethoxy-4
      cresol (TMC), was isolated from the solid-state cultured mycelium of A.
      cinnamomea. According to the results obtained from cell wound healing, cell
      migration and invasion assays, TMC effectively suppressed movement, migration and
      invasion of lung cancer cells at the dosage of 5-40 MUM, which was non-toxic to
      A549 cells. In addition, TMC reduced protein expression of Akt, MMP-2 and MMP-9
      and enhanced E-cadherin and TIMP-1 protein expression, which are known to
      regulate cell adhesion, migration and invasion. Taken together, TMC effectively
      suppresses movement, migration and invasion of lung cancer cells, and achieves an
      anti-cancer metastasis effect. 

PMID- 25951810
TI  - The BH3-only protein BID impairs the p38-mediated stress response and promotes
      hepatocarcinogenesis during chronic liver injury in mice.
AB  - Apoptosis is critical for maintaining tissue homeostasis, and apoptosis evasion
      is considered as a hallmark of cancer. However, increasing evidence also suggests
      that proapoptotic molecules can contribute to the development of cancer,
      including liver cancer. The aim of this study was to further clarify the role of
      the proapoptotic B-cell lymphoma 2 homology domain 3 (BH3)-only protein BH3
      interacting-domain death agonist (BID) for chronic liver injury (CLI) and
      hepatocarcinogenesis (HCG). Loss of BID significantly delayed tumor development
      in two mouse models of Fah-mediated and HBsTg-driven HCG, suggesting a tumor
      promoting effect of BID. Liver injury as well as basal and mitogen-stimulated
      hepatocyte proliferation were not modulated by BID. Moreover, there was no in
      vivo or in vitro evidence that BID was involved in DNA damage response in
      hepatocytes and hepatoma cells. Our data revealed that CLI was associated with
      strong activation of oxidative stress (OS) response and that BID impaired full
      activation of p38 after OS. CONCLUSION: We provide evidence that the tumor
      promoting function of BID in CLI is not related to enhanced proliferation or an
      impaired DNA damage response. In contrast, BID suppresses p38 activity and
      facilitates malignant transformation of hepatocytes.

PMID- 25951811
TI  - Identification of SPAG9 as a novel JAK2 fusion partner gene in pediatric acute
      lymphoblastic leukemia with t(9;17)(p24;q21).
AB  - We have identified a novel SPAG9-JAK2 fusion in a B-cell precursor acute
      lymphoblastic leukemia (ALL) with t(9;17)(p24;q21) and a poor outcome, using
      paired-end transcriptome sequencing. Homozygous and hemizygous deletions of
      CDKN2A/2B, and hemizygous deletions of PAX5, BTG1, CDK6, ADARB2, and IKZF1 were
      also identified by multiple ligation-dependent probe amplification and single
      nucleotide polymorphism array analyses. Having both a tyrosine kinase-activating
      rearrangement and genomic lesions affecting lymphoid transcription factors
      suggested that the leukemia was of the Philadelphia chromosome (Ph)/BCR-ABL1-like
      ALL subtype and that JAK2 inhibitors might be able to overcome this aggressive
      ALL with SPAG9-JAK2.

PMID- 25951813
TI  - Comparison of Transesophageal and Intracardiac Electrophysiologic Studies for the
      Diagnosis of Childhood Supraventricular Tachycardias.
AB  - In this study, we aimed to compare the results of transesophageal
      electrophysiologic studies (TEEPS) and intracardiac electrophysiologic studies
      (IEPS) in a cohort of pediatric patients with SVTs. The medical records of
      children aged between 0 and 18 years who underwent TEEPS between January 2007 and
      June 2012 were systematically reviewed, and those without pre-excitation and who
      underwent subsequent IEPS were identified. Post-procedural diagnoses were
      compared for compatibility. A total of 162 patients were included in the study
      with a mean age at diagnosis 11.6 +/- 3.6 years. Tachycardia was induced in 152
      patients by TEEPS and in 154 patients by IEPS. Overall, in 147 patients,
      tachycardia was induced by both TEEPS and IEPS. Diagnoses were compatible in 135
      out of 147 patients (91.8 %). Nine out of the 12 patients with discrepant results
      were diagnosed with atrioventricular-reentrant tachycardia (AVRT) and three with
      atrioventricular nodal reentrant tachycardia (AVNRT) after TEEPS. Following IEPS,
      TEEPS diagnosis of AVRT was revised to typical AVNRT in 5 patients and atypical
      AVNRT in 4 patients. Two of the 3 patients who were diagnosed as having AVNRT
      following TEEPS were confirmed to have atrial tachycardia after IEPS, while the
      other patient was diagnosed with AVRT. Tachycardia terminated spontaneously in 3
      patients, while overdrive pacing was attempted to terminate the tachycardia in
      149 patients, with a success rate of 93.2 % (139/149). The diagnostic
      compatibility between TEEPS and IEPS is quite high. A diagnostic discrepancy
      mostly occurs in patients diagnosed with AVRT by TEEPS, and the possibility of
      atypical AVNRT should be considered in patients with a VA >=70 ms to avoid such
      discrepancies.

PMID- 25951814
TI  - Maternal Hypertension During Pregnancy and the Risk of Congenital Heart Defects
      in Offspring: A Systematic Review and Meta-analysis.
AB  - Maternal hypertension is common during pregnancy, and multiple studies have
      reported on an association between maternal hypertension and congenital heart
      defects (CHDs) in offspring; however, there is variability in the quality of
      these studies. A systematic review and meta-analysis was conducted on the
      associations between untreated and treated maternal hypertension and the risk of
      CHDs, evaluating CHDs overall as well as specific CHD subtypes. A systematic
      search of peer-reviewed articles published before August 2013 identified 16
      studies evaluating the associations between untreated and treated maternal
      hypertension and CHDs. Summary relative risk (RR) estimates were calculated using
      fixed-effects models and random-effects models. Significant associations were
      observed between maternal hypertension and overall CHDs, for both treated [RR
      2.0; 95 % confidence interval (CI) 1.5, 2.7] and untreated (RR 1.4; 95 % CI 1.2,
      1.7) hypertension, as well as for overall hypertension regardless of treatment
      status (RR 1.8; 95 % CI 1.5, 2.2). The magnitude of effect was similar for the
      majority of CHD subtypes evaluated. The effects were also similar among women
      with hypertension who used one of multiple specific hypertension medications.
      There was no evidence of publication bias, and our results were robust to several
      factors considered in sensitivity analyses (e.g., source of exposure data,
      adjustment for potential confounders, and study design). Maternal hypertension
      was associated with CHDs. By understanding the specific mechanisms involved,
      appropriate strategies may be developed to reduce this risk, in order to prevent
      CHDs.

PMID- 25951815
TI  - Cardiovascular Response to Exercise Testing in Children and Adolescents Late
      After Kawasaki Disease According to Coronary Condition Upon Onset.
AB  - Multiple cardiovascular sequelae have been reported late after Kawasaki disease
      (KD), especially in patients with coronary artery lesions. In this perspective,
      we hypothesized that exercise response was altered after KD in patients with
      coronary aneurysms (CAA-KD) compared to those without history of coronary
      aneurysms (NS-KD). This study is a post hoc analysis of exercise data from an
      international multicenter trial. A group of 133 CAA-KD subjects was compared to a
      group of 117 NS-KD subjects. Subjects underwent a Bruce treadmill test followed
      to maximal exertion. Heart rate (HR), systolic blood pressure (SBP), and
      diastolic blood pressure (DBP) were assessed at each stage of the test including
      recovery. Myocardial perfusion was evaluated by stress and rest Tc-99m sestamibi
      SPECT imaging. Endurance time was similar between NS-KD and CAA-KD (11.3 +/- 2.6
      vs. 11.0 +/- 2.6 min; p = 0.343). HR, SBP, and DBP responses to exercise were
      similar between groups (p = 0.075-0.942). Myocardial perfusion defects were
      present in 16.5 % CAA-KD versus 22.2 % NS-KD (p = 0.255). Analysis based on
      myocardial perfusion status identified a lower heart rate at 1 min into recovery
      as well as lower DBP at 1 and 5 min into recovery in patients with abnormal SPECT
      imaging (p = 0.017-0.042). Compared to patients without CA involvement, the
      presence of coronary aneurysms at the subacute phase of KD does not induce a
      differential effect on exercise parameters. In contrast, exercise-induced
      myocardial perfusion defect late after the onset of KD correlates with abnormal
      recovery parameters.

PMID- 25951817
TI  - Memories of an East German scientist.

PMID- 25951816
TI  - Fabrication of ordered arrays of micro- and nanoscale features with control over
      their shape and size via templated solid-state dewetting.
AB  - Templated solid-state dewetting of single-crystal films has been shown to be used
      to produce regular patterns of various shapes. However, the materials for which
      this patterning method is applicable, and the size range of the patterns produced
      are still limited. Here, it is shown that ordered arrays of micro- and nanoscale
      features can be produced with control over their shape and size via solid-state
      dewetting of patches patterned from single-crystal palladium and nickel films of
      different thicknesses and orientations. The shape and size characteristics of the
      patterns are found to be widely controllable with varying the shape, width,
      thickness, and orientation of the initial patches. The morphological evolution of
      the patches is also dependent on the film material, with different dewetting
      behaviors observed in palladium and nickel films. The mechanisms underlying the
      pattern formation are explained in terms of the influence on Rayleigh-like
      instability of the patch geometry and the surface energy anisotropy of the film
      material. This mechanistic understanding of pattern formation can be used to
      design patches for the precise fabrication of micro- and nanoscale structures
      with the desired shapes and feature sizes. 

PMID- 25951818
TI  - Phytochemical regulation of Fyn and AMPK signaling circuitry.
AB  - During the past decades, phytochemical terpenoids, polyphenols, lignans,
      flavonoids, and alkaloids have been identified as antioxidative and
      cytoprotective agents. Adenosine monophosphate-activated protein kinase (AMPK) is
      a kinase that controls redox-state and oxidative stress in the cell, and serves
      as a key molecule regulating energy metabolism. Many phytochemicals directly or
      indirectly alter the AMPK pathway in distinct manners, exerting catabolic
      metabolism. Some of them are considered promising in the treatment of metabolic
      diseases such as type II diabetes, obesity, and hyperlipidemia. Another important
      kinase that regulates energy metabolism is Fyn kinase, a member of the Src family
      kinases that plays a role in various cellular responses such as insulin
      signaling, cell growth, oxidative stress and apoptosis. Phytochemical inhibition
      of Fyn leads to AMPK-mediated protection of the cell in association with
      increased antioxidative capacity and mitochondrial biogenesis. The kinases may
      work together to form a signaling circuitry for the homeostasis of energy
      conservation and expenditure, and may serve as targets of phytochemicals. This
      review is intended as a compilation of recent advancements in the pharmacological
      research of phytochemicals targeting Fyn and AMPK circuitry, providing
      information for the prevention and treatment of metabolic diseases and the
      accompanying tissue injuries. 

PMID- 25951820
TI  - The effectiveness of interventions to achieve co-ordinated multidisciplinary care
      and reduce hospital use for people with chronic diseases: study protocol for a
      systematic review of reviews.
AB  - BACKGROUND: The burden of chronic disease on patients and the health service is
      growing. Current health policy emphasises the need for services which provide
      integrated and co-ordinated care for patients with chronic diseases, but there is
      uncertainty about which integrated care interventions and service models may be
      most effective. This review of reviews aims to synthesise the available evidence
      about the effectiveness of such interventions and service models in terms of
      patient experience of health and social care, the use of hospital and other
      health resources, and the associated costs. METHODS/DESIGN: We will search
      MEDLINE, Embase, ASSIA, PsycINFO, HMIC, CINAHL, Cochrane Library (including HTA
      Database, DARE and Cochrane Database of Systematic Reviews), EPPI-Centre, TRIP,
      and Health Economic Evaluations databases for English language systematic reviews
      and meta-analyses published since 2000 that have evaluated the effectiveness of
      integrated care interventions for patients with chronic diseases. Interventions
      must deliver care that crosses the boundary between at least two health and/or
      social care settings. Outcomes of interest are healthcare resource use, patient
      quality of life/satisfaction, costs, and care co-ordination. Data from eligible
      reviews will be extracted by two independent reviewers and will include study
      details, the design, delivery and co-ordination of interventions, and
      methodological quality. Evidence synthesis will focus on a narrative overview of
      interventions and their effectiveness. DISCUSSION: The review aims to summarise
      the evidence base about the effectiveness of integrated care interventions and
      service models and describe how interventions have been organised, co-ordinated,
      and delivered. The findings have the potential to impact on the commissioning of
      health and social care services in the UK which aim to provide integrated and co
      ordinated care for patients with chronic disease and multimorbidity. SYSTEMATIC
      REVIEW REGISTRATION: PROSPERO CRD42015016458 .

PMID- 25951821
TI  - Effect of whole body vibration in energy expenditure and perceived exertion
      during intense squat exercise.
AB  - PURPOSE: The purpose of this study was to investigate the effect of whole body
      vibration in oxygen uptake during intense squatting exercise with an added weight
      and whole body vibration compared with the same exercise without vibration.
      METHODS: Nine male sub- jects performed three trials of dynamic squatting with an
      additional load of 50% of their body weight during 3 min. One trial without
      vibration, one trial with the frequency of 40 Hz and amplitude of 2 mm and one
      trial with the frequency of 40 Hz and amplitude of 4 mm. RESULTS: The results
      showed no difference between the three experimental trials in relative and
      absolute oxygen uptake. However, the metabolic power and energy expended in whole
      body vibration (2 mm) were significantly different from exercise without
      vibration. The data analysis also showed a significant difference in rating of
      perceived exertion with whole body vibration (4 mm) compared with the exercise
      without vibration. Results showed that the addition of vibration stimulus has an
      increase in the energy expenditure particularly with 40 Hz and 2 mm amplitude,
      suggesting that the high metabolic power during heavy resistance training could
      be increased by the addition of vibration stimulation. CONCLUSIONS: Involuntary
      contractions generated by the vibration can be used by coaches to increase the
      intensity of heavy resistance training or to increase the energy expended during
      the workouts if the goal is a decrease of body mass.

PMID- 25951822
TI  - Genomic prediction of disease occurrence using producer-recorded health data: a
      comparison of methods.
AB  - BACKGROUND: Genetic selection has been successful in achieving increased
      production in dairy cattle; however, corresponding declines in fitness traits
      have been documented. Selection for fitness traits is more difficult, since they
      have low heritabilities and are influenced by various non-genetic factors. The
      objective of this paper was to investigate the predictive ability of two-stage
      and single-step genomic selection methods applied to health data collected from
      on-farm computer systems in the U.S. METHODS: Implementation of single-trait and
      two-trait sire models was investigated using BayesA and single-step methods for
      mastitis and somatic cell score. Variance components were estimated. The complete
      dataset was divided into training and validation sets to perform model
      comparison. Estimated sire breeding values were used to estimate the number of
      daughters expected to develop mastitis. Predictive ability of each model was
      assessed by the sum of chi(2) values that compared predicted and observed numbers
      of daughters with mastitis and the proportion of wrong predictions. RESULTS:
      According to the model applied, estimated heritabilities of liability to mastitis
      ranged from 0.05 (SD=0.02) to 0.11 (SD=0.03) and estimated heritabilities of
      somatic cell score ranged from 0.08 (SD=0.01) to 0.18 (SD=0.03). Posterior mean
      of genetic correlation between mastitis and somatic cell score was equal to 0.63
      (SD=0.17). The single-step method had the best predictive ability. Conversely,
      the smallest number of wrong predictions was obtained with the univariate BayesA
      model. The best model fit was found for single-step and pedigree-based models.
      Bivariate single-step analysis had a better predictive ability than bivariate
      BayesA; however, the latter led to the smallest number of wrong predictions.
      CONCLUSIONS: Genomic data improved our ability to predict animal breeding values.
      Performance of genomic selection methods depends on a multitude of factors.
      Heritability of traits and reliability of genotyped individuals has a large
      impact on the performance of genomic evaluation methods. Given the current
      characteristics of producer-recorded health data, single-step methods have
      several advantages compared to two-step methods.

PMID- 25951819
TI  - Independent evidence for an association between general cognitive ability and a
      genetic locus for educational attainment.
AB  - Cognitive deficits and reduced educational achievement are common in psychiatric
      illness; understanding the genetic basis of cognitive and educational deficits
      may be informative about the etiology of psychiatric disorders. A recent, large
      genome-wide association study (GWAS) reported a genome-wide significant locus for
      years of education, which subsequently demonstrated association to general
      cognitive ability ("g") in overlapping cohorts. The current study was designed to
      test whether GWAS hits for educational attainment are involved in general
      cognitive ability in an independent, large-scale collection of cohorts. Using
      cohorts in the Cognitive Genomics Consortium (COGENT; up to 20,495 healthy
      individuals), we examined the relationship between g and variants associated with
      educational attainment. We next conducted meta-analyses with 24,189 individuals
      with neurocognitive data from the educational attainment studies, and then with
      53,188 largely independent individuals from a recent GWAS of cognition. A SNP
      (rs1906252) located at chromosome 6q16.1, previously associated with years of
      schooling, was significantly associated with g (P = 1.47 * 10(-4) ) in COGENT.
      The first joint analysis of 43,381 non-overlapping individuals for this a priori
      designated locus was strongly significant (P = 4.94 * 10(-7) ), and the second
      joint analysis of 68,159 non-overlapping individuals was even more robust (P =
      1.65 * 10(-9) ). These results provide independent replication, in a large-scale
      dataset, of a genetic locus associated with cognitive function and education. As
      sample sizes grow, cognitive GWAS will identify increasing numbers of associated
      loci, as has been accomplished in other polygenic quantitative traits, which may
      be relevant to psychiatric illness.

PMID- 25951823
TI  - Expression of brain derived-neurotrophic factor and granulocyte-colony
      stimulating factor in the urothelium: relation with voiding function.
AB  - BACKGROUND: We designed this experiment to elucidate the relationship between the
      expression of brain derived-neurotrophic factor (BDNF), the expression of
      granulocyte-colony stimulating factor (G-CSF), and the development of overactive
      bladder (OAB). In our previous study, the urothelium was observed to be more than
      a simple mechanosensory receptor and was found to be a potential therapeutic
      target for OAB. Moreover, neuregulin-1 and BDNF were found to be potential new
      biomarkers of OAB. Here, we investigated the relationship between changes in the
      voiding pattern and the expression of BDNF and G-CSF in the urothelium and
      evaluated the effects of 5-hydroxymethyl tolterodine (5-HMT) on rats with bladder
      outlet obstruction (BOO). METHODS: A total of 100 Sprague-Dawley rats were
      divided into the following groups: 20 control rats; 40 BOO rats; and 40 BOO rats
      administered 5-HMT (0.1 mg/kg). After BOO was induced for 4 weeks, the rats were
      assessed by cystometrography. The changes in BDNF and G-CSF expression were
      examined in both separated urothelial tissues and in cultured urothelial cells by
      reverse transcription polymerase chain reaction (RT-PCR). RESULTS: BOO rats
      showed increased non-voiding activity [NVA; (number/10 voidings)] and bladder
      weight and decreased micturition volume (MV), micturition interval (MI), and
      micturition time (MT) relative to the controls. Moreover, the 5-HMT
      administration rats showed decreased NVA and bladder weight and increased MV and
      MI in comparison to the BOO rats. BDNF and G-CSF expression was increased in BOO
      rats and decreased following 5-HMT administration. In this model, voiding
      dysfunction developed as a result of BOO. As a therapeutic agent for OAB, the
      administration of 5-HMT improved the voiding dysfunction. CONCLUSIONS: BDNF and G
      CSF might modulate voiding patterns through micturition pathways and might be
      involved only in the urothelium. Moreover, the expression of both genes in the
      urothelium might be related to voiding dysfunction in OAB patients. Thus, the
      urothelium has an important role in the manifestation of voiding symptoms.

PMID- 25951824
TI  - Dentin Sialophosphoprotein-derived Proteins in the Dental Pulp.
AB  - Porcine dentin sialophosphoprotein (DSPP), the most abundant noncollagenous
      protein in dentin, is critical for proper mineralization of tooth dentin. DSPP is
      processed by proteases into 3 major domains: dentin sialoprotein (DSP), dentin
      glycoprotein (DGP), and dentin phosphoprotein (DPP). There are at least 2 mRNA
      variants expressed from the Dspp gene: one encodes the full-length DSPP protein
      (DSP+DGP+DPP); the other encodes only DSP. The shorter transcript is generated
      through the use of a polyadenylation signal within intron 4, immediately
      following the DSP coding region (DGP and DPP are encoded by exon 5). We
      fractionated DSPP-derived proteins from the dental pulp of developing porcine
      incisors using heparin chromatography. DSP was identified, but little DPP could
      be detected in any fractions. BMP-1 digestion of DSPP-derived proteins extracted
      from dental pulp did not generate new DPP bands on sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (indicating an absence of intact DSPP),
      although the results suggested another BMP-1 cleavage site within DSP. We further
      purified DSPP-derived protein by reversed-phase high-performance liquid
      chromatography. Its amino acid composition was similar to DSP. Expression of the
      full-length Dspp mRNA by quantitative real-time polymerase chain reaction
      analysis was significantly higher in odontoblasts than in pulp, while expression
      of the DSP-only mRNA was almost equal in odontoblasts and in the body of the
      pulp. Expression of the full-length Dspp mRNA was also significantly higher than
      the expression of DSP-only mRNA in odontoblasts. Both the full-length and the DSP
      only Dspp mRNA showed only trace expression in the pulp tip. We conclude that use
      of the 3' polyadenylation signal in exon 5 predominates in fully differentiated
      odontoblasts, while both polyadenylation signals are used throughout odontoblast
      differentiation. 

PMID- 25951826
TI  - Health potential of a low glycaemic index diet.

PMID- 25951825
TI  - Long-term Management of Moderate to Severe Plaque Psoriasis Patients With
      Etanercept: A Case Series.
AB  - BACKGROUND: Currently, etanercept (ETN) safety and efficacy in patients with
      moderate to severe plaque psoriasis (PsO) has been reported up to 5 years.
      OBJECTIVE: To present a case series of PsO patients receiving continuous ETN
      therapy for 7 or more years. METHODS: Physicians collected data retrospectively
      from 52 patient charts from 5 centres across Canada. RESULTS: Patients in this
      case series had PsO an average of 31.5 years. Nearly half of patients also had
      psoriatic arthritis (24/52). All patients demonstrated sustained improvement in
      Psoriasis Area and Severity Index (PASI) and percentage of affected body surface
      area (BSA) following ETN treatment. Of the 52 patients, 33 have been receiving
      ETN for 10 years or more. CONCLUSION: The clinical experience described in this
      case series report suggests maintenance of ETN efficacy in PsO patients who
      receive therapy for 7 years or more and indicates that patients can be
      successfully managed with long-term ETN therapy.

PMID- 25951828
TI  - The second International Genomic Medicine Conference (2nd IGMC, 2013): brief
      report and outcome.

PMID- 25951827
TI  - Cilostazol attenuates murine hepatic ischemia and reperfusion injury via heme
      oxygenase-dependent activation of mitochondrial biogenesis.
AB  - Hepatic ischemia-reperfusion (I/R) can cause hepatocellular injury associated
      with the inflammatory response and mitochondrial dysfunction. We studied the
      protective effects of the phosphodiesterase inhibitor cilostazol in hepatic I/R
      and the roles of mitochondria and the Nrf2/heme oxygenase-1 (HO-1) system. Wild
      type, Hmox1(-/-), or Nrf2(-/-) mice were subjected to hepatic I/R in the absence
      or presence of cilostazol followed by measurements of liver injury. Primary
      hepatocytes were subjected to cilostazol with the HO-1 inhibitor ZnPP, or Nrf2
      specific siRNA, followed by assessment of mitochondrial biogenesis.
      Preconditioning with cilostazol prior to hepatic I/R protected against
      hepatocellular injury and mitochondrial dysfunction. Cilostazol reduced the serum
      levels of alanine aminotransferase, TNF-alpha, and liver myeloperoxidase content
      relative to control I/R-treated mice. In primary hepatocytes, cilostazol
      increased the expression of HO-1, and markers of mitochondrial biogenesis, PGC
      1alpha, NRF-1, and TFAM, induced the mitochondrial proteins COX III and COX IV
      and increased mtDNA and mitochondria content. Pretreatment of primary hepatocytes
      with ZnPP inhibited cilostazol-induced PGC-1alpha, NRF-1, and TFAM mRNA
      expression and reduced mtDNA and mitochondria content. Genetic silencing of Nrf2
      prevented the induction of HO-1 and mitochondrial biogenesis by cilostazol in
      HepG2 cells. Cilostazol induced hepatic HO-1 production and mitochondrial
      biogenesis in wild-type mice, but not in Hmox1(-/-) or Nrf2(-/-) mice, and failed
      to protect against liver injury in Nrf2(-/-) mice. These results suggest that I/R
      injury can impair hepatic mitochondrial function, which can be reversed by
      cilostazol treatment. These results also suggest that cilostazol-induced
      mitochondrial biogenesis was mediated by an Nrf-2- and HO-1-dependent pathway. 

PMID- 25951829
TI  - A prospective study validating a clinical scoring system and demonstrating
      phenotypical-genotypical correlations in Silver-Russell syndrome.
AB  - BACKGROUND: Multiple clinical scoring systems have been proposed for Silver
      Russell syndrome (SRS). Here we aimed to test a clinical scoring system for SRS
      and to analyse the correlation between (epi)genotype and phenotype. SUBJECTS AND
      METHODS: Sixty-nine patients were examined by two physicians. Clinical scores
      were generated for all patients, with a new, six-item scoring system: (1) small
      for gestational age, birth length and/or weight <=-2SDS, (2) postnatal growth
      retardation (height <=-2SDS), (3) relative macrocephaly at birth, (4) body
      asymmetry, (5) feeding difficulties and/or body mass index (BMI) <=-2SDS in
      toddlers; (6) protruding forehead at the age of 1-3 years. Subjects were
      considered to have likely SRS if they met at least four of these six criteria.
      Molecular investigations were performed blind to the clinical data. RESULTS: The
      69 patients were classified into two groups (Likely-SRS (n=60), Unlikely-SRS
      (n=9)). Forty-six Likely-SRS patients (76.7%) displayed either 11p15 ICR1
      hypomethylation (n=35; 58.3%) or maternal UPD of chromosome 7 (mUPD7) (n=11;
      18.3%). Eight Unlikely-SRS patients had neither ICR1 hypomethylation nor mUPD7,
      whereas one patient had mUPD7. The clinical score and molecular results yielded
      four groups that differed significantly overall and for individual scoring system
      factors. Further molecular screening led identifying chromosomal abnormalities in
      Likely-SRS-double-negative and Unlikely-SRS groups. Four Likely-SRS-double
      negative patients carried a DLK1/GTL2 IG-DMR hypomethylation, a mUPD16; a mUPD20
      and a de novo 1q21 microdeletion. CONCLUSIONS: This new scoring system is very
      sensitive (98%) for the detection of patients with SRS with demonstrated
      molecular abnormalities. Given its clinical and molecular heterogeneity, SRS
      could be considered as a spectrum.

PMID- 25951830
TI  - The clinical application of genome-wide sequencing for monogenic diseases in
      Canada: Position Statement of the Canadian College of Medical Geneticists.
AB  - PURPOSE AND SCOPE: The aim of this Position Statement is to provide
      recommendations for Canadian medical geneticists, clinical laboratory
      geneticists, genetic counsellors and other physicians regarding the use of genome
      wide sequencing of germline DNA in the context of clinical genetic diagnosis.
      This statement has been developed to facilitate the clinical translation and
      development of best practices for clinical genome-wide sequencing for genetic
      diagnosis of monogenic diseases in Canada; it does not address the clinical
      application of this technology in other fields such as molecular investigation of
      cancer or for population screening of healthy individuals. METHODS OF STATEMENT
      DEVELOPMENT: Two multidisciplinary groups consisting of medical geneticists,
      clinical laboratory geneticists, genetic counsellors, ethicists, lawyers and
      genetic researchers were assembled to review existing literature and guidelines
      on genome-wide sequencing for clinical genetic diagnosis in the context of
      monogenic diseases, and to make recommendations relevant to the Canadian context.
      The statement was circulated for comment to the Canadian College of Medical
      Geneticists (CCMG) membership-at-large and, following incorporation of feedback,
      approved by the CCMG Board of Directors. The CCMG is a Canadian organisation
      responsible for certifying medical geneticists and clinical laboratory
      geneticists, and for establishing professional and ethical standards for clinical
      genetics services in Canada. RESULTS AND CONCLUSIONS: Recommendations include (1)
      clinical genome-wide sequencing is an appropriate approach in the diagnostic
      assessment of a patient for whom there is suspicion of a significant monogenic
      disease that is associated with a high degree of genetic heterogeneity, or where
      specific genetic tests have failed to provide a diagnosis; (2) until the benefits
      of reporting incidental findings are established, we do not endorse the
      intentional clinical analysis of disease-associated genes other than those linked
      to the primary indication; and (3) clinicians should provide genetic counselling
      and obtain informed consent prior to undertaking clinical genome-wide sequencing.
      Counselling should include discussion of the limitations of testing, likelihood
      and implications of diagnosis and incidental findings, and the potential need for
      further analysis to facilitate clinical interpretation, including studies
      performed in a research setting. These recommendations will be routinely re
      evaluated as knowledge of diagnostic and clinical utility of clinical genome-wide
      sequencing improves. While the document was developed to direct practice in
      Canada, the applicability of the statement is broader and will be of interest to
      clinicians and health jurisdictions internationally.

PMID- 25951832
TI  - I-AIM framework for point-of-care gastric ultrasound.

PMID- 25951831
TI  - Electroencephalographic coherence and cortical acetylcholine during ketamine
      induced unconsciousness.
AB  - BACKGROUND: There is limited understanding of cortical neurochemistry and
      cortical connectivity during ketamine anaesthesia. We conducted a systematic
      study to investigate the effects of ketamine on cortical acetylcholine (ACh) and
      electroencephalographic coherence. METHODS: Male Sprague-Dawley rats (n=11) were
      implanted with electrodes to record electroencephalogram (EEG) from frontal,
      parietal, and occipital cortices, and with a microdialysis guide cannula for
      simultaneous measurement of ACh concentrations in prefrontal cortex before,
      during, and after ketamine anaesthesia. Coherence and power spectral density
      computed from the EEG, and ACh concentrations, were compared between conscious
      and unconscious states. Loss of righting reflex was used as a surrogate for
      unconsciousness. RESULTS: Ketamine-induced unconsciousness was associated with a
      global reduction of power (P=0.02) in higher gamma bandwidths (>65 Hz), a global
      reduction of coherence (P<=0.01) across a broad frequency range (0.5-250 Hz), and
      a significant increase in ACh concentrations (P=0.01) in the prefrontal cortex.
      Compared with the unconscious state, recovery of righting reflex was marked by a
      further increase in ACh concentrations (P=0.0007), global increases in power in
      theta (4-10 Hz; P=0.03) and low gamma frequencies (25-55 Hz; P=0.0001), and
      increase in power (P<=0.01) and coherence (P<=0.002) in higher gamma frequencies
      (65-250 Hz). Acetylcholine concentrations, coherence, and spectral properties
      returned to baseline levels after a prolonged recovery period. CONCLUSIONS:
      Ketamine-induced unconsciousness is characterized by suppression of high
      frequency gamma activity and a breakdown of cortical coherence, despite increased
      cholinergic tone in the cortex.

PMID- 25951834
TI  - Upregulation of K(2P)3.1 K+ Current Causes Action Potential Shortening in
      Patients With Chronic Atrial Fibrillation.
AB  - BACKGROUND: Antiarrhythmic management of atrial fibrillation (AF) remains a major
      clinical challenge. Mechanism-based approaches to AF therapy are sought to
      increase effectiveness and to provide individualized patient care. K(2P)3.1 (TASK
      1 [tandem of P domains in a weak inward-rectifying K+ channel-related acid
      sensitive K+ channel-1]) 2-pore-domain K+ (K(2P)) channels have been implicated
      in action potential regulation in animal models. However, their role in the
      pathophysiology and treatment of paroxysmal and chronic patients with AF is
      unknown. METHODS AND RESULTS: Right and left atrial tissue was obtained from
      patients with paroxysmal or chronic AF and from control subjects in sinus rhythm.
      Ion channel expression was analyzed by quantitative real-time polymerase chain
      reaction and Western blot. Membrane currents and action potentials were recorded
      using voltage- and current-clamp techniques. K(2P)3.1 subunits exhibited
      predominantly atrial expression, and atrial K(2P)3.1 transcript levels were
      highest among functional K(2P) channels. K(2P)3.1 mRNA and protein levels were
      increased in chronic AF. Enhancement of corresponding currents in the right
      atrium resulted in shortened action potential duration at 90% of repolarization
      (APD90) compared with patients in sinus rhythm. In contrast, K(2P)3.1 expression
      was not significantly affected in subjects with paroxysmal AF. Pharmacological
      K(2P)3.1 inhibition prolonged APD90 in atrial myocytes from patients with chronic
      AF to values observed among control subjects in sinus rhythm. CONCLUSIONS:
      Enhancement of atrium-selective K(2P)3.1 currents contributes to APD shortening
      in patients with chronic AF, and K(2P)3.1 channel inhibition reverses AF-related
      APD shortening. These results highlight the potential of K(2P)3.1 as a novel drug
      target for mechanism-based AF therapy.

PMID- 25951833
TI  - Facility-Level Variation in Hospitalization, Mortality, and Costs in the 30 Days
      After Percutaneous Coronary Intervention: Insights on Short-Term Healthcare Value
      From the Veterans Affairs Clinical Assessment, Reporting, and Tracking System (VA
      CART) Program.
AB  - BACKGROUND: Policies to reduce unnecessary hospitalizations after percutaneous
      coronary intervention (PCI) are intended to improve healthcare value by reducing
      costs while maintaining patient outcomes. Whether facility-level hospitalization
      rates after PCI are associated with cost of care is unknown. METHODS AND RESULTS:
      We studied 32,080 patients who received PCI at any 1 of 62 Veterans Affairs
      hospitals from 2008 to 2011. We identified facility outliers for 30-day risk
      standardized hospitalization, mortality, and cost. Compared with the risk
      standardized average, 2 hospitals (3.2%) had a lower-than-expected
      hospitalization rate, and 2 hospitals (3.2%) had a higher-than-expected
      hospitalization rate. We observed no statistically significant variation in
      facility-level risk-standardized mortality. The facility-level unadjusted median
      per patient 30-day total cost was $23,820 (interquartile range, $19,604-$29,958).
      Compared with the risk-standardized average, 17 hospitals (27.4%) had lower-than
      expected costs, and 14 hospitals (22.6%) had higher-than-expected costs. At the
      facility level, the index PCI accounted for 83.1% of the total cost (range, 60.3%
      92.2%), whereas hospitalization after PCI accounted for only 5.8% (range, 2.0%
      12.7%) of the 30-day total cost. Facilities with higher hospitalization rates
      were not more expensive (Spearman rho=0.16; 95% confidence interval, -0.09 to
      0.39; P=0.21). CONCLUSIONS: In this national study, hospitalizations in the 30
      day after PCI accounted for only 5.8% of 30-day cost, and facility-level cost was
      not correlated with hospitalization rates. This challenges the focus on reducing
      hospitalizations after PCI as an effective means of improving healthcare value.
      Opportunities remain to improve PCI value by reducing the variation in total cost
      of PCI without compromising patient outcomes.

PMID- 25951835
TI  - Resistance of MMP9 and TIMP1 to endotoxin tolerance.
AB  - Inflammatory cytokines activate tissue collagenases such as matrix
      metalloproteinases (MMPs). MMPs are antagonized by tissue inhibitors of
      metalloproteinases (TIMPs) that attempt to regulate excessive collagenase
      activity during inflammatory conditions. During chronic inflammatory conditions,
      induction of endotoxin tolerance negatively regulates the cytokine response in an
      attempt to curtail excessive host tissue damage. However, little is known about
      how downregulation of inflammatory cytokines during endotoxin tolerance regulates
      MMP activities. In this study, human monocyte-derived macrophages were either
      sensitized or further challenged to induce tolerance with lipopolysaccharide
      (LPS) from Porphyromonas gingivalis (PgLPS) or Escherichia coli (EcLPS).
      Inflammatory cytokines, such as TNF-alpha and IL-1beta, and levels of MMP9 and
      TIMP1 were analyzed by a combination of cytometric bead array, western
      blot/gelatin zymography and real-time RT-PCR. Functional blocking with anti-TLR4
      but not with anti-TLR2 significantly downregulated TNF-alpha and IL-1beta.
      However, MMP9 levels were not inhibited by toll-like receptor (TLR) blocking.
      Interestingly, endotoxin tolerance significantly upregulated TIMP1 relative to
      MMP9 and downmodulated MMP9 secretion and its enzymatic activity. These results
      suggest that regulatory mechanisms such as induction of endotoxin tolerance could
      inhibit MMP activities and could facilitate restoring host tissue homeostasis. 

PMID- 25951837
TI  - Statistical Study of Beam-Induced Motion of Gold Adatoms by a Scanning TEM.
AB  - In order to achieve reliable structural characterization by transmission electron
      microscopy, beam-induced structural changes should be clarified for any target
      material system. As an example, the movement of heavy adatoms on a thin carbon
      support has been repeatedly reported under the electron beam while the underlying
      reason for such motion is still in debate. By applying statistical analysis to
      the group behavior of gold adatoms, we investigated their motion under different
      beam conditions and detected features corresponding to beam-induced motion, under
      typical scanning transmission electron microscopy observation conditions. Our
      results are consistent with the theoretical prediction proposed by Egerton
      (2013). 

PMID- 25951838
TI  - Practice Update: What Professionals Who Are Not Brain Injury Specialists Need to
      Know About Intimate Partner Violence-Related Traumatic Brain Injury.
AB  - There is growing recognition of the risk for traumatic brain injury (TBI) among
      victims and survivors of intimate partner violence (IPV). A wide range of
      physically abusive behaviors may lead to injuries to the head or neck and place
      an individual at risk for a TBI. The purpose of this article is to consolidate
      current research and present practical guidelines for professionals, who are not
      brain injury specialists, but work with clients who may have sustained a TBI in
      the context of IPV. Recommendations are provided for TBI risk screening, making
      appropriate referrals, and providing services in light of a potential TBI.

PMID- 25951836
TI  - Functional optical coherence tomography: principles and progress.
AB  - In the past decade, several functional extensions of optical coherence tomography
      (OCT) have emerged, and this review highlights key advances in instrumentation,
      theoretical analysis, signal processing and clinical application of these
      extensions. We review five principal extensions: Doppler OCT (DOCT), polarization
      sensitive OCT (PS-OCT), optical coherence elastography (OCE), spectroscopic OCT
      (SOCT), and molecular imaging OCT. The former three have been further developed
      with studies in both ex vivo and in vivo human tissues. This review emphasizes
      the newer techniques of SOCT and molecular imaging OCT, which show excellent
      potential for clinical application but have yet to be well reviewed in the
      literature. SOCT elucidates tissue characteristics, such as oxygenation and
      carcinogenesis, by detecting wavelength-dependent absorption and scattering of
      light in tissues. While SOCT measures endogenous biochemical distributions,
      molecular imaging OCT detects exogenous molecular contrast agents. These newer
      advances in functional OCT broaden the potential clinical application of OCT by
      providing novel ways to understand tissue activity that cannot be accomplished by
      other current imaging methodologies. 

PMID- 25951839
TI  - Clinician Responses to Client Traumas: A Chronological Review of Constructs and
      Terminology.
AB  - This paper presents a chronologically-organized review of various concepts and
      constructs in the literature describing professional burnout, compassion fatigue,
      secondary traumatic stress reactions, as well as other related terms and
      constructs that have been used to describe these experiences among clinical
      practitioners and other social service professionals. A timeline will provide a
      graphic illustration of the historical relationships between the concepts under
      examination. This paper begins with a review of practitioner-related stress that
      primarily results from interaction with clients, followed by an examination of
      professional burnout, which is thought to result largely from environmentally
      related issues. Finally, the paper concludes with a discussion of posttraumatic
      growth and compassion satisfaction.

PMID- 25951840
TI  - Efficacy of Bystander Programs to Prevent Dating Abuse Among Youth and Young
      Adults: A Review of the Literature.
AB  - Estimates suggest that between 10% and 25% of adolescents have experienced some
      form of physical violence within a dating relationship, and one in four college
      age women experiences attempted or completed sexual violence on campus. Bystander
      programs focus on equipping young adults with the skills to safely intervene when
      they witness behaviors that can result in dating abuse. This approach is promoted
      for its capacity both to transform community norms that contribute to dating
      abuse and to foster more positive social interactions among youth, however, there
      has been limited review of the literature on the outcomes of bystander programs.
      Therefore, this article provides an in-depth systematic literature review, which
      describes the content and program components of bystander programs and summarizes
      what is currently known about the impact of bystander interventions on
      participants' behaviors and attitudes. Results indicate that bystander programs
      are promising from the standpoint of increasing young adults' willingness to
      intervene and confidence in their ability to intervene when they witness dating
      or sexual violence, however, the utilization of actual bystander behaviors was
      less straightforward. Implications for prevention practice and for future
      research are presented.

PMID- 25951841
TI  - Is Anybody Listening? The Literature on the Dialogical Process of Child Sexual
      Abuse Disclosure Reviewed.
AB  - We conducted an exploratory review of the current literature on child sexual
      abuse disclosure in everyday contexts. The aim of this study was to provide an
      overview of relevant publications on the process of child sexual abuse
      disclosure, in order to generate new directions for future research and clinical
      practice. The findings of the exploratory review show that disclosure is a
      relational process, which is renegotiated by each interaction and evolves over an
      extended period of time. The characteristics and reactions of the interaction
      partner appear to be as critical to this process as the behavior and words of
      children themselves. Methodological limitations of the review and the
      publications are discussed, as well as directions for future research and
      implications for practice.

PMID- 25951842
TI  - Biomechanical parameters in lower limbs during natural walking and Nordic walking
      at different speeds.
AB  - PURPOSE: Nordic Walking (NW) is a sport that has a number of benefits as a
      rehabilitation method. It is performed with specially designed poles and has been
      often recommended as a physical activity that helps reduce the load to limbs.
      However, some studies have suggested that these findings might be erroneous.
      STUDY AIM: The aim of this paper was to compare the kinematic, kinetic and
      dynamic parameters of lower limbs between Natural Walking (W) and Nordic Walking
      (NW) at both low and high walking speeds. METHODS: The study used a registration
      system, BTS Smart software and Kistler platform. Eleven subjects walked along a
      15-metre path at low (below 2 m?s-1) and high (over 2 m?s-1) walking speeds. The
      Davis model was employed for calculations of kinematic, kinetic and dynamic
      parameters of lower limbs. RESULTS: With constant speed, the support given by
      Nordic Walking poles does not make the stroke longer and there is no change in
      pelvic rotation either. The only change observed was much bigger pelvic
      anteversion in the sagittal plane during fast NW. There were no changes in
      forces, power and muscle torques in lower limbs. CONCLUSIONS: The study found no
      differences in kinematic, kinetic and dynamic parameters between Natural Walking
      (W) and Nordic Walking (NW). Higher speeds generate greater ground reaction
      forces and muscle torques in lower limbs. Gait parameters depend on walking speed
      rather than on walking style.

PMID- 25951843
TI  - Isolation of Lactic Acid Bacteria Showing Antioxidative and Probiotic Activities
      from Kimchi and Infant Feces.
AB  - The purpose of this study was to investigate lactic acid bacteria with
      antioxidative and probiotic activities isolated from Korean healthy infant feces
      and kimchi. Isolates A1, A2, S1, S2, and S3 were assigned to Lactobacillus sp.
      and isolates A3, A4, E1, E2, E3, and E4 were assigned to Leuconostoc sp. on the
      basis of their physiological properties and 16S ribosomal DNA sequence analysis.
      Most strains were confirmed as safe bioresources through nonhemolytic activities
      and non-production of harmful enzymes such as beta-glucosidase, beta-
      glucuronidase and tryptophanase. The 11 isolates showed different resistance to
      acid and bile acids. In addition, they exhibited antibacterial activity against
      foodborne bacteria, especially Bacillus cereus, Listeria monocytogenes, and
      Escherichia coli. Furthermore, all strains showed significantly high levels of
      hydrophobicity. The antioxidant effects of culture filtrates of the 11 strains
      included 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging capacity, 2.2'-
      azino-bis (2-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical cation
      scavenging activity, and superoxide dismutase activity. The results revealed that
      most of the culture filtrates have effective scavenging activity for DPPH and
      ABTS radicals. All strains appeared to have effective superoxide dismutase
      activity. In conclusion, the isolated strains A1, A3, S1, and S3 have significant
      probiotic activities applicable to the development of functional foods and health
      related products. These strains might also contribute to preventing and
      controlling several diseases associated with oxidative stress, when used as
      probiotics. 

PMID- 25951844
TI  - Polypropylene Bundle Attached Multilayered Stigeoclonium Biofilms Cultivated in
      Untreated Sewage Generate High Biomass and Lipid Productivity.
AB  - The potential of microalgae biofuel has not been realized because of the low
      productivity and high costs associated with the current cultivation systems. In
      this study, a new low-cost and transparent attachment material was tested for
      cultivation of a filamentous algal strain, Stigeoclonium sp., isolated from
      wastewater. Initially, the different materials tested for Stigeoclonium
      cultivation in untreated wastewater were nylon mesh, polyethylene mesh,
      polypropylene bundle (PB), polycarbonate plate, and viscose rayon. Among the
      materials tested, PB led to a firm attachment, high biomass (53.22 g/m(2), dry
      cell weight), and total lipid yield (5.8 g/m(2)) with no perceivable change in
      FAME profile. The Stigeoclonium-dominated biofilm consisted of bacteria and
      extracellular polysaccharide, which helped in biofilm formation and for effective
      wastewater treatment (viz., removal efficiency of total nitrogen and total
      phosphorus corresponded to ~38% and ~90%, respectively). PB also demonstrated
      high yields under multilayered cultivation in a single reactor treating
      wastewater. Hence, this system has several advantages over traditional suspended
      and attached systems, with possibility of increasing areal productivity three
      times using Stigeoclonium sp. Therefore, multilayered attached growth algal
      cultivation systems seem to be the future cultivation model for large-scale
      biodiesel production and wastewater treatment.

PMID- 25951845
TI  - Enhanced Production of Epothilone by Immobilized Sorangium cellulosum in Porous
      Ceramics.
AB  - Epothilone, which is produced by the myxobacterium Sorangium cellulosum,
      contributes significant value in medicinal development. However, under submerged
      culture conditions, S. cellulosum will accumulate to form bacterial clumps, which
      hinder nutrient and metabolite transportation. Therefore, the production of
      epothilone by liquid fermentation is limited. In this study, diatomite-based
      porous ceramics were made from diatomite, paraffin, and poremaking agent (saw
      dust). Appropriate methods to modify the porous ceramics were also identified.
      After optimizing the preparation and modification conditions, we determined the
      optimal prescription to prepare high-performance porous ceramics. The structure
      of porous ceramics can provide a solid surface area where S. cellulosum can grow
      and metabolize to prevent the formation of bacterial clumps. S. cellulosum cells
      that do not form clumps will change their erratic metabolic behavior under
      submerged culture conditions. As a result, the unstable production of epothilone
      by this strain can be changed in the fermentation process, and the purpose of
      increasing epothilone production can be achieved. After 8 days of fermentation
      under optimized conditions, the epothilone yield reached 90.2 mg/l, which was
      increased four times compared with the fermentation without porous ceramics. 

PMID- 25951846
TI  - Novel Endoxylanases of the Moderately Thermophilic Polysaccharide-Degrading
      Bacterium Melioribacter roseus.
AB  - Three endoxylanase-encoding genes from the moderately themophilic
      chemoorganotrophic bacterium Melioribacter roseus were cloned and expressed in
      Escherichia coli. Genes xyl2091 (Mros_2091) and xyl2495 (Mros_2495) encode GH10
      family hydrolases, whereas xyl2090 (Mros_2090) represents the GH30 family. In
      addition to catalytic domains, Xyl2090 and Xyl2091 contain carbohydrate-binding
      modules that could facilitate their binding to xylans and Por sorting domains
      associated with the sorting of proteins from the periplasm to the outer membrane,
      where they are covalently attached. Recombinant endoxylanase Xyl2495 exhibited a
      high specific activity of 1,920 U/mg on birchwood xylan at 40 degrees C. It is
      active at low temperatures, exhibiting more than 30% of the maximal activity even
      at 0 degrees C. Endoxylanases Xyl2090 and Xyl2091 have lower specific activities
      but higher temperature optima at 80 degrees C and 65 degrees C, respectively.
      Analysis of xylan hydrolysis products revealed that Xyl2090 generates xylo
      oligosaccharides longer than xylopentaose. Xylose and xylobiose are the major
      products of xylan hydrolysis by the recombinant Xyl2091 and Xyl2495. No activity
      against cellulose was observed for all enzymes. The presence of three xylanases
      ensures efficient xylan hydrolysis by M. roseus. The highly processive "free"
      endoxylanase Xyl2495 could hydrolyze xylan under moderate temperatures. Xylan
      hydrolysis at elevated temperatures could be accomplished by concerted action of
      two cell-bound xylanases; Xyl2090 that probably degrades xylans to long xylo
      oligosaccharides, and Xyl2091 hydrolyzing them to xylose and xylobiose. The new
      endoxylanases could be useful for saccharification of lignocellulosic biomass in
      biofuels production, bleaching of paper pulp, and obtaining low molecular weight
      xylooligosaccharides.

PMID- 25951847
TI  - Rapid and Specific Detection of Acidovorax avenae subsp. citrulli Using SYBR
      Green-Based Real-Time PCR Amplification of the YD-Repeat Protein Gene.
AB  - The aim of this study was to develop a SYBR Green-based real-time PCR assay for
      the rapid, specific, and sensitive detection of Acidovorax avenae subsp.
      citrulli, which causes bacterial fruit blotch (BFB), a serious disease of
      cucurbit plants. The molecular and serological methods currently available for
      the detection of this pathogen are insufficiently sensitive and specific. Thus, a
      novel SYBR Green-based real-time PCR assay targeting the YD-repeat protein gene
      of A. avenae subsp. citrulli was developed. The specificity of the primer set was
      evaluated using DNA purified from 6 isolates of A. avenae subsp. citrulli, 7
      other Acidovorax species, and 22 of non-targeted strains, including pathogens and
      non-pathogens. The AC158F/R primer set amplified a single band of the expected
      size from genomic DNA obtained from the A. avenae subsp. citrulli strains but not
      from the genomic DNA of other Acidovorax species, including that of other
      bacterial genera. Using this assay, it was possible to detect at least one
      genomeequivalents of the cloned amplified target DNA using 5 * 10(0) fg/MUl of
      purified genomic DNA per reaction or using a calibrated cell suspension, with 6.5
      colony-forming units per reaction being employed. In addition, this assay is a
      highly sensitive and reliable method for identifying and quantifying the target
      pathogen in infected samples that does not require DNA extraction. Therefore, we
      suggest that this approach is suitable for the rapid and efficient diagnosis of
      A. avenae subsp. citrulli contaminations of seed lots and plants. 

PMID- 25951848
TI  - Benign fibrous histiocytoma of parietal bone: case report and review of the
      literature.
AB  - A benign fibrous histiocytoma with primary site of origin in the parietal bone
      has not yet been reported in the literature. We report here a case concerning a
      12-year-old girl with a 14-month history of an enlarging parietal bone mass. The
      tumor was excised after removal of the cortical bone and resection of the tumor
      surrounding the cortical bone erosion using pre-plasticity titanium repair. Both
      postoperative histopathological examination and immunohistochemical analysis were
      consistent with a benign fibrous histiocytoma. No clinical or computed tomography
      (CT) radiological signs of tumor recurrence and/or metastasis were observed at 12
      months. Although a primary benign fibrous histiocytoma of the parietal bone is a
      rare tumor, it should be considered as a potential diagnosis for any cranial
      tumor. Surgical intervention is the most effective treatment technique for a
      benign fibrous histiocytoma. 

PMID- 25951849
TI  - Gene-environment interactions and obesity: recent developments and future
      directions.
AB  - Obesity, a major public health concern, is a multifactorial disease caused by
      both environmental and genetic factors. Although recent genome-wide association
      studies have identified many loci related to obesity or body mass index, the
      identified variants explain only a small proportion of the heritability of
      obesity. Better understanding of the interplay between genetic and environmental
      factors is the basis for developing effective personalized obesity prevention and
      management strategies. This article reviews recent advances in identifying gene
      environment interactions related to obesity and describes epidemiological designs
      and newly developed statistical approaches to characterizing and discovering gene
      environment interactions on obesity risk. 

PMID- 25951850
TI  - A BEME (Best Evidence in Medical Education) systematic review of the use of
      workplace-based assessment in identifying and remediating poor performance among
      postgraduate medical trainees.
AB  - BACKGROUND: Workplace-based assessments were designed to facilitate observation
      and structure feedback on the performance of trainees in real-time clinical
      settings and scenarios. Research in workplace-based assessments has primarily
      centred on understanding psychometric qualities and performance improvement
      impacts of trainees generally. An area that is far less understood is the use of
      workplace-based assessments for trainees who may not be performing at expected or
      desired standards, referred to within the literature as trainees 'in difficulty'
      or 'underperforming'. In healthcare systems that increasingly depend on service
      provided by junior doctors, early detection (and remediation) of poor performance
      is essential. However, barriers to successful implementation of workplace-based
      assessments (WBAs) in this context include a misunderstanding of the use and
      purpose of these formative assessment tools. This review aims to explore the
      impact - or effectiveness - of workplace-based assessment on the identification
      of poor performance and to determine those conditions that support and enable
      detection, i.e. whether by routine or targeted use where poor performance is
      suspected. The review also aims to explore what effect (if any) the use of WBA
      may have on remediation or on changing clinical practice. The personal impact of
      the detection of poor performance on trainees and/or trainers may also be
      explored. METHODS/DESIGN: Using BEME (Best Evidence in Medical Education)
      Collaboration review guidelines, nine databases will be searched for English
      language records. Studies examining interventions for workplace-based assessment
      either routinely or in relation to poor performance will be included. Independent
      agreement (kappa .80) will be achieved using a randomly selected set of records
      prior to commencement of screening and data extraction using a BEME coding sheet
      modified as applicable (Buckley et al., Med Teach 31:282-98, 2009) as this has
      been used in previous WBA systematic reviews (Miller and Archer, BMJ
      doi:10.1136/bmj.c5064, 2010) allowing for more rigorous comparisons with the
      published literature. Educational outcomes will be evaluated using Kirkpatrick's
      framework of educational outcomes using Barr's adaptations (Barr et al.,
      Evaluations of interprofessional education; a United Kingdom review of health and
      social care, 2000) for medical education research. DISCUSSION: Our study will
      contribute to an ongoing international debate regarding the applicability of
      workplace-based assessments as a meaningful formative assessment approach within
      the context of postgraduate medical education. SYSTEMATIC REVIEW REGISTRATION:
      The review has been registered by the BEME Collaboration
      www.bemecollaboration.org .

PMID- 25951851
TI  - Magnetically Guided Fabrication of Multilayered Iron
      Oxide/Polycaprolactone/Gelatin Nanofibrous Structures for Tissue Engineering and
      Theranostic Application.
AB  - A persistent challenge in tissue engineering is the fabrication of manipulatable
      scaffolds for implantation in clinical treatments and use in disease models for
      drug screening. Electrospinning of nanofibrous membranes is an emerging
      technology in artificial extracellular matrix (ECM) design that can offer
      precisely tunable microenvironments upon assembly into three-dimensional (3D)
      scaffolds that mimic the in vivo ECM structure. In this study, we report a facile
      and versatile strategy for preparing 3D multilayered constructs from
      Fe3O4/polycaprolactone (PCL)/gelatin nanofibrous membranes. This method combines
      membrane assembly with noncontact magnetic force to preserve the mechanical
      integrity and interconnectivity of the 3D scaffolds. An ordered layer structure
      can be achieved using a magnetic control technique through the addition of
      magnetic nanoparticles into the PCL/gelatin nanofibers. We first verified the
      magnetic properties and structures of magnetic nanofibers according to X-ray
      diffraction, hysteresis, scanning electron microscopy, and transmission electron
      microscopy. We tested the potential toxicity and osteogenic differentiation of
      mesenchymal stem cells seeded on the layered scaffolds. To add further
      functionality to the scaffolds, the membranes were coated with silver
      nanoparticles and shown to inhibit the growth of Escherichia coli and
      Staphylococcus aureus, which are responsible for most cases of infection-related
      implant failure. Finally, we tested the utility of magnetic membranes implanted
      in an animal model as a contrast agent for magnetic resonance imaging. Scaffolds
      formed using the presented magnetically guided fabrication strategy have the
      potential to mimic the structure and function of human tissues and also may be
      applied in disease models to study cell-cell interactions. 

PMID- 25951852
TI  - Automatic Evaluation of Collagen Fiber Directions from Polarized Light Microscopy
      Images.
AB  - Mechanical properties of the arterial wall depend largely on orientation and
      density of collagen fiber bundles. Several methods have been developed for
      observation of collagen orientation and density; the most frequently applied
      collagen-specific manual approach is based on polarized light (PL). However, it
      is very time consuming and the results are operator dependent. We have proposed a
      new automated method for evaluation of collagen fiber direction from two
      dimensional polarized light microscopy images (2D PLM). The algorithm has been
      verified against artificial images and validated against manual measurements.
      Finally the collagen content has been estimated. The proposed algorithm was
      capable of estimating orientation of some 35 k points in 15 min when applied to
      aortic tissue and over 500 k points in 35 min for Achilles tendon. The average
      angular disagreement between each operator and the algorithm was -9.3+/-8.6
      degrees  and -3.8+/-8.6 degrees  in the case of aortic tissue and -1.6+/-6.4
      degrees  and 2.6+/-7.8 degrees  for Achilles tendon. Estimated mean collagen
      content was 30.3+/-5.8% and 94.3+/-2.7% for aortic media and Achilles tendon,
      respectively. The proposed automated approach is operator independent and several
      orders faster than manual measurements and therefore has the potential to replace
      manual measurements of collagen orientation via PLM. 

PMID- 25951853
TI  - Update on the surgical management of breast cancer.
AB  - The surgical management of breast cancer has undergone continuous and profound
      changes over the last three decades. For patients with early stage breast cancer,
      breast-conserving surgery followed by radiation therapy has been definitively
      validated as a safe alternative to radical mastectomy, with similar survival
      rates, better cosmetic outcomes and acceptable rates of local recurrence. Thanks
      to the improvements in diagnostic work-up, as well as the wider diffusion of
      screening programs and efforts in patient and physician education, tumors are
      more often detected at an early stage, furtherly facilitating the widespread use
      of breast conserving techniques. Breast-conserving surgery has been introduced
      also in the treatment of patients with locally advanced tumors after tumor
      downsizing with preoperative chemotherapy, with acceptable rates of ipsilateral
      breast tumor recurrence. When performing breast-conserving surgery all efforts
      should be made to ensure negative surgical margins in order minimize the risk of
      ipsilateral breast tumor recurrence as they are associated with worse distant
      disease-free and breast cancer- specific survival rates. The recent introduction
      of "oncoplastic techniques", that may allow more extensive excisions of the
      breast without compromising the cosmetic results, has furtherly increased the use
      of breast-conserving procedures. Mastectomy remains a valid surgical alternative
      in selected cases and is usually associated with immediate reconstructive
      procedures. Staging of the axilla has also gradually evolved toward less
      aggressive approaches with the adoption of sentinel node biopsy, but several
      controversies still remain about completion of axillary lymph node dissection in
      patients with a pathologic positivity in sentinel lymph node biopsy. The present
      work will highlight the benefits and unresolved issues of the different surgical
      treatment options in breast cancer and axillary treatment.

PMID- 25951854
TI  - Porphyromonas gingivalis Suppresses Differentiation and Increases Apoptosis of
      Osteoblasts From New Zealand Obese Mice.
AB  - BACKGROUND: Metabolic syndrome (MetS), a complex cluster of risk factors for
      chronic diseases such as cardiovascular disease, is observed to be increasingly
      associated with periodontal disease. However, the fundamental contribution of
      periodontal bacteria to periodontal bone loss in patients with MetS remains
      unclear. The aim of the present study is to analyze the effect of Porphyromonas
      gingivalis on differentiation of primary osteoblasts from New Zealand obese (NZO)
      mice, a model for MetS, compared with C57 Black 6 JAX (C57BL/6J) mice
      osteoblasts. METHODS: Primary calvarial osteoblasts, isolated from 3-day-old NZO
      and control C57BL/6J mice, were stimulated with P. gingivalis. Proliferation was
      quantified by 5-bromo-2'-deoxyuridine incorporation. Cell cycle and early and
      late apoptosis were measured by flow cytometry. Gene expression was determined by
      real-time polymerase chain reaction (RT-PCR). RESULTS: Twelve hours after P.
      gingivalis stimulation, NZO osteoblasts showed significantly decreased
      proliferation (P <=0.01) with increased G2 cell cycle phase compared with normal
      osteoblasts. Flow cytometry analysis demonstrated significant (P <=0.01) increase
      of early apoptotic cells (annexin V positive) and late apoptosis (caspase 3
      activity) in NZO cells compared with control cells at 3 and 6 hours after
      stimulation. No significant lactate dehydrogenase release was found after P.
      gingivalis stimulation. RT-PCR data showed significantly suppressed expression (P
      <=0.01) of collagen 1, osteocalcin, and Runt-related transcription factor 2 in
      NZO cells compared with normal osteoblasts. CONCLUSIONS: The present data
      demonstrate that P. gingivalis downregulates proliferation and promotes apoptosis
      in primary NZO osteoblasts, unlike C57BL/6J osteoblasts. Also, suppressed
      osteoblastic marker expression in NZO cells may contribute to pathogenesis of
      periodontitis, suggesting a similar process in patients with MetS.

PMID- 25951855
TI  - Laterality versus jumping performance in men and women.
AB  - PURPOSE: The aim of this study was to investigate relationships between
      functional asymmetry of lower limbs, taking into account morphological features
      of the feet, and jumping ability in men and women. METHODS: The study population
      consisted of 56 subjects, 30 women (age: 20.29 +/- 0.59 years; body mass: 58.13
      +/- 4.58 kg, body height: 165.60 +/- 5.03 cm) and 26 men (age: 20.41 +/- 0.78
      years, body mass: 78.39 +/- 8.42 kg, body height: 181.15 +/- 6.52 cm). The
      measurements of longitudinal arches were performed with the plan- tographic
      method on the basis of Clarke's angle mapped on a computer foot print. The
      measurements of jumping performance during bilateral (two legs) and unilateral
      (single-leg) counter movement jump (CMJ) were done on force plate. All subjects
      jumped three times each type of jump (total 9 jumps): three right leg, three left
      leg and three two legs. We put the test results through a detailed statistical
      analysis with the Statistica 8.0. The t-test for dependent variables and the
      Wilcoxon signed-rank test for divergent variances of the fea- tures compared. The
      analysis of relationships between the chosen podometric and plantographic
      features and jumping performance was conducted on the basis of the Pearson
      product-moment correlation coefficient (for the features which presented normal
      distribution, according to the Shapiro-Wilk test). RESULTS: The correlations
      between values of height of single-leg jumps (right and left) and bilateral
      jumps, and foot indices were found in few cases only in men who had greater
      values of jump height with the non-dominant limb. We did not find a significant
      difference in jumping ability between the dominant limb and the non-dominant limb
      in women. We found bilateral deficits in jumping ability in the study groups,
      though we did not find significant differences (P <= 0.05) between the values for
      women (a mean of 6.5%) and for men (a mean of 8.4%). CONCLUSION: We found
      significant gender differences of the correlations between the values of height
      of jumps (single-leg and bilateral jumps) and foot indices.

PMID- 25951856
TI  - Intramuscular hepatitis B immunoglobulins for reinfection control after liver
      transplantation: a cost-saving alternative.
AB  - AIM: We explore the effectiveness and cost-effectiveness of intramuscular versus
      intravenous hepatitis B immunoglobulins (HBIG-IV vs HBIG-IM) to prevent
      reinfection with the hepatitis B virus after orthotopic liver transplantation.
      PATIENTS & METHODS: Overall, 14 patients had orthotopic liver transplantation in
      2003-2013 at Ghent University Hospital for HBV-related liver disease. On average
      32 months after transplantation patients switched from high-dose HBIG-IV to low
      dose HBIG-IM, always in combination with a nucleos(t)ide analog. RESULTS: Seven
      patients were switched so far. No significant differences between HBIG-IV and
      HBIG-IM were found in HBsAg and hepatitis B virus-DNA. CONCLUSION: Switching
      patients from HBIG-IV to HBIG-IM can be done safely if well monitored. Net yearly
      savings for the healthcare payer were ?5000 for each patient switched to HBIG-IM.

PMID- 25951858
TI  - Novibacillus thermophilus gen. nov., sp. nov., a Gram-staining-negative and
      moderately thermophilic member of the family Thermoactinomycetaceae.
AB  - Two Gram-staining-negative, facultatively anaerobic bacterial strains, SG-1T and
      SG-2, were isolated from a saline soil sample and a compost sample, respectively.
      The cells were non-motile rods that occurred singly or in chains, and endospores
      were not observed under tested growth conditions. Optimum growth occurred at 50 
      degrees C, pH 7.5-8.0 and with 5-7 % (w/v) NaCl. The DNA G+C content was 49.5
      50.5 mol%. The strains contained MK-7 as the predominant menaquinone and iso-C15
      : 0 and anteiso-C15 : 0 as the major fatty acids. The polar lipids consisted
      mainly of diphosphatidylglycerol and phosphatidylglycerol. The cell-wall
      peptidoglycan type was A1gamma (meso-DAP direct). Phylogenetic analyses revealed
      that the new isolates belonged to the family Thermoactinomycetaceae, exhibiting
      low 16S rRNA gene sequence similarity (90.8-91.3 %) to the nearest type strain,
      Mechercharimyces asporophorigenens YM11-542T, and formed a well-supported lineage
      that was clearly distinguished from all currently described genera in this
      family. Based on our polyphasic taxonomic characterization, we propose that
      strains SG-1T and SG-2 represent a novel genus and species within the family
      Thermoactinomycetaceae, for which we propose the name Novibacillus thermophilus
      gen. nov., sp. nov. The type strain of Novibacillus thermophilus is SG-1T ( =
      KCTC 33118T = CGMCC 1.12771T).

PMID- 25951857
TI  - Effects of tofacitinib on lymphocyte sub-populations, CMV and EBV viral load in
      patients with plaque psoriasis.
AB  - BACKGROUND: Plaque psoriasis is a debilitating skin condition that affects
      approximately 2% of the adult population and for which there is currently no
      cure. Tofacitinib is an oral Janus kinase inhibitor that is being investigated
      for psoriasis. METHODS: The design of this study has been reported previously
      (NCT00678210). Patients with moderate to severe chronic plaque psoriasis received
      tofacitinib (2 mg, 5 mg, or 15 mg) or placebo, twice daily, for 12 weeks.
      Lymphocyte sub-populations, cytomegalovirus (CMV) and Epstein-Barr virus (EBV)
      DNA were measured at baseline and up to Week 12. RESULTS: Tofacitinib was
      associated with modest, dose-dependent percentage increases from baseline in
      median B cell count at Week 4 (24-68%) and Week 12 (18-43%) and percentage
      reductions from baseline in median natural killer cell count at Week 4 (11-40%).
      The proportion of patients with detectable CMV and EBV DNA (defined as >0
      copies/500 ng total DNA) increased post-baseline in tofacitinib-treated patients.
      However, multivariate analyses found no relationship between changes in CMV or
      EBV viral load and changes in lymphocyte sub-populations or tofacitinib
      treatment. CONCLUSIONS: Twelve weeks of treatment with tofacitinib had no
      clinically significant effects on CMV or EBV viral load, suggesting that
      lymphocyte sub-populations critical to the response to chronic viral infections
      and viral reactivation were not significantly affected. Replication of these
      findings during long-term use of tofacitinib will allow confirmation of this
      observation.

PMID- 25951859
TI  - Kibdelosporangium lantanae sp. nov., isolated from the rhizosphere soil of an
      ornamental plant, Lantana camara L.
AB  - Strain XMU 506T, isolated from the rhizosphere soil of an ornamental plant,
      Lantana camara L., collected from Xiamen City, China, was identified using a
      polyphasic approach to clarify its taxonomic position. The aerial mycelium of
      this organism formed long straight or curved chains of spores and sporangium-like
      structures. The optimum growth occurred at 28-30  degrees C, pH 7.0 with 0-1%
      NaCl. Strain XMU 506T showed the highest 16S rRNA gene sequence similarity
      (96.5%) to Kibdelosporangium philippinense DSM 44226T, and formed a monophyletic
      clade in the 16S rRNA gene phylogenetic tree together with the type strains of
      the genus Kibdelosporangium. The chemotaxonomic properties further supported the
      assignment of strain XMU 506T to the genus Kibdelosporangium: meso-diaminopimelic
      acid was the diagnostic amino acid in the cell wall peptidoglycan; mycolic acids
      were not present in the cell wall; the whole-cell hydrolysates contained
      arabinose, galactose, glucose and ribose. The major menaquinone was MK-9(H4); the
      phospholipids of the isolate comprised phosphatidylethanolamine, OH
      phosphatidylethanolamine, diphosphatidylglycerol and unidentified amino-, glyco-
      and phospholipids; the major fatty acids of the strain were iso-C16 : 0, C17 : 1
      omega6c and iso-C16 : 1 H. The G+C content of genomic DNA was 67.3 mol%. Based on
      the results of phylogenetic analysis, phenotypic and genotypic characterization,
      strain XMU 506T represents a novel species in the genus Kibdelosporangium, for
      which the name Kibdelosporangium lantanae sp. nov. is proposed. The type strain
      is XMU 506T ( = KCTC 29675T = MCCC 1K00430T).

PMID- 25951860
TI  - Leuconostoc rapi sp. nov., isolated from sous-vide-cooked rutabaga.
AB  - A Gram-stain-positive, ovoid, lactic acid bacterium, strain LMG 27676T, was
      isolated from a spoiled sous-vide-cooked rutabaga. 16S rRNA gene sequence
      analysis indicated that the novel strain belongs to the genus Leuconostoc, with
      Leuconostoc kimchii and Leuconostoc miyukkimchii as the nearest neighbours (99.1
      and 98.8% 16S rRNA gene sequence similarity towards the type strain,
      respectively). Phylogenetic analysis of the 16S rRNA gene, multilocus sequence
      analysis of the pheS, rpoA and atpA genes, and biochemical and genotypic
      characteristics allowed differentiation of strain LMG 27676T from all established
      species of the genus Leuconostoc. Strain LMG 27676T ( = R-50029T = MHB 277T = DSM
      27776T) therefore represents the type strain of a novel species, for which the
      name Leuconostoc rapi sp. nov. is proposed.

PMID- 25951862
TI  - Updating Rule 15 of the International Code of Nomenclature of Bacteria.
AB  - The wording of Rule 15 as originally published in the 1975 and 1990 revisions of
      the International Code of Nomenclature of Bacteria with regard to the definition
      ofnomenclatural typeswas not clearly expressed and was modified by the Judicial
      Commission in 2008. However, there is a difference between the wording as
      proposed and that accepted. On reflection there is justification for re-examining
      both the proposed and the accepted wording. 

PMID- 25951861
TI  - Nocardioides antarcticus sp. nov., isolated from marine sediment.
AB  - Strain M-SA3-94T, an aerobic, Gram-stain-positive, ovoid- to rod-shaped, non
      motile bacterium, was isolated from the marine sediment of Ardley cove, King
      George Island, Antarctica. Strain M-SA3-94T grew optimally at pH 5.0-6.0, 20 
      degrees C and in the presence of 1.0 % (w/v) NaCl. Phylogenetic analysis, based
      on 16S rRNA gene sequences, indicated that strain M-SA3-94T belonged to the genus
      Nocardioides in the family Nocardioidaceae, clustering with Nocardioides
      plantarum NCIMB 12834T, Nocardioides ginsengagri BX5-10T, Nocardioides
      marinquilinus CL-GY44T and Nocardioides lianchengensis D94-1T (with 96.1 %, 95.9
      %, 94.5 % and 94.7 % 16S rRNA gene sequence similarity, respectively). The
      chemotaxonomic properties of strain M-SA3-94T were similar to those of members of
      the genus Nocardioides with validly published names. The major fatty acid was iso
      C16 : 0. The polar lipid pattern contained diphosphatidylglycerol,
      phosphatidylglycerol and three unknown phospholipids. The diagnostic diamino acid
      in the cell-wall peptidoglycan was ll-2, 6-diaminopimelic acid. MK-8(H4) was the
      predominant menaquinone and the DNA G+C content of this strain was 66.7 mol%. On
      the basis of these phenotypic, phylogenetic and chemotaxonomic data, strain M-SA3
      94T represents a novel species of the genus Nocardioides, for which the name
      Nocardioides antarcticus sp. nov. is proposed. The type strain is M-SA3-94T ( =
      CCTCC AB2014053T = LMG 28254T). 

PMID- 25951863
TI  - [Assessment of the impact over one year of a workplace health promotion programme
      in the province of Bergamo].
AB  - OBJECTIVES: To estimate short-term effects of integrated health promotion in the
      workplace within the framework of the Bergamo WHP (Workplace Health Promotion)
      network, which involves 94 companies and about 21,000 workers. METHODS: A
      controlled non-randomized, before-after evaluation was carried out. Data were
      collected through anonymous questionnaires before (t0) and after participation in
      a 12-month health promotion programme (t1). The "control" group consisted of
      workers of companies participating in the programme who had not yet undertaken
      any interventions in the theme areas covered by the assessment. RESULTS: In the
      workers participating in the programme, positive early effects (after 12 months)
      were related to intake of food providing protection (fruit and vegetables) and
      increased rates of smoking cessation. The effects were more evident in males and
      in white collars. The physical activity and alcohol consumption trends went in
      the desired direction and with more effects than in the non-participating group,
      but without statistical significance. In the short term, no evident changes in
      events of road injury risk or in the quality of personal relationships were seen,
      probably due to the small size of the sample involved in these study areas.
      CONCLUSIONS: The results, although within the methodological limitations of the
      study, showed that after 12 months there was a reduction in some important risk
      factors for chronic diseases in workers participating in the programme,
      particularly for fruit and vegetable intake and smoking cessation. It will be
      important to monitor the effects of the programme on other risk factors in the
      medium and long term, and also the impact of employment status and gender so as
      to adjust the programme interventions accordingly. Cooperation with
      occupational/authorized physicians with use of their data collected from health
      surveillance, together with a limited set of general risk factor indicators,
      would be a desirable development for further studies.

PMID- 25951864
TI  - Young and burnt? Italian contribution to the international BurnOut Syndrome Study
      (BOSS) among residents in psychiatry.
AB  - BACKGROUND: The Burnout Syndrome (BS) is a common condition among health care
      professionals, yet data concerning its prevalence and associated factors among
      psychiatric residents are lacking. OBJECTIVES: To report the results of the
      Italian contribution to "BOSS", an international multicentre research project
      aiming at estimating the burden of BS among residents in psychiatry, and at
      identifying factors contributing to its development and prevention. METHODS:
      Cross-sectional study. The BOSS online questionnaire, which collected socio
      demographic data and five psychometric tools (MBI-GS, AWLS, PHQ-9, SIBQ, BFI),
      was administered electronically to 180 Italian residents in psychiatry. Simple
      and multiple linear regressions were performed to analyse data. RESULTS: 108
      questionnaires provided data for the study (response rate: 60%). Mean age: 30.5
      +/- 3.7 years. Eighty percent of the sample were female. A moderate level of BS
      emerged, related to work conditions, absence of major depression, satisfaction
      with pay or less academic activity. Only 0.9% (N=1) of the sample showed PHQ-9
      scores suggestive of major depression, while lifetime suicidal ideation was
      admitted by 16% of residents. For the three dimensions of the MBI-GS, Italian
      sample scores were consistent with previously published results concerning pooled
      data in a French-Croatian sample, reporting moderate levels of BS. Higher
      workload, symptoms of depression and lower satisfaction predicted higher levels
      of Emotional Exhaustion and Cynicism. CONCLUSIONS: Italian residents in
      psychiatry showed overall moderate levels of BS, related to workload and work
      organization. Other alerts of psychic distress were found among participants,
      namely symptoms of depression, suicidal ideation and use of psychotropic
      medications.

PMID- 25951866
TI  - [The relationship between work-family interface and turnover intention: a study
      in a sample of Italian nurses].
AB  - BACKGROUND: Work-family interface is an increasingly central research topic in
      organizational studies, and it is considered particularly relevant in healthcare
      contexts. Several studies on nursing staff showed the role of work-family
      conflict (WFC) and enrichment (WFE) in influencing work dynamics. OBJECTIVES: The
      present study aims  at examining the relationship between work-family interface
      (in terms of conflict and enrichment) and turnover intentions (TI), in a sample
      of Italian nurses. METHODS: A sample of 478 nurses filled in a self-report
      questionnaire, consisting of different scales based on the international
      literature. RESULTS: Regression analysis, with TI as dependent variable, showed a
      positive relationship with WFC and a negative relationship with WFE. CONCLUSIONS:
      The results of the study confirmed that WFC was a potential predictor of TI, able
      to influence the tendency to desire a new job and look for a new occupation. WFE
      also had a role in influencing this outcome: perceptions of enrichment from work
      to family can contribute to reducing TI. The results of the present study
      indicate the importance of developing working contexts that will foster work
      family conciliation, through policies and practices able to reduce the negative
      interference from work to family, and to increase opportunities to improve and
      develop new skills that can be used also in other contexts.

PMID- 25951867
TI  - [A survey on injuries among nurses and nursing students: a descriptive
      epidemiologic analysis between 2002 and 2012 at a University Hospital].
AB  - BACKGROUND: Biological risk is the main occupational hazard in hospitals (40-50%
      of the total). More than 130,000 injuries occur every year in Italy and nurses
      are the most affected occupational category. OBJECTIVES: This study evaluated the
      incidence of injuries related to biological risk in nurses and nursing students
      in the University Hospital of Ferrara, how they occur, the knowledge on the topic
      and on behaviour during the department's activity. METHODS: A retrospective study
      involving a sample of 8 departments (selected for the occurrence of more than 30
      biological injuries between 1st January 2002 and 31 December 2012) recorded
      injuries related to biological risk; subsequently a cross-sectional survey was
      carried out through a questionnaire administered to nurses and nursing students.
      RESULTS: 909 biological accidents were reported (81.18% in nurses and 18.82% in
      students). Blood was the main biological material involved (83.72% of cases),
      mostly by percutaneous exposure (84.16%). According to the questionnaire, 53% of
      subjects reported having had at least one injury during their career, and 5.72%
      did not report it; 46% reported doing risky procedures (re-capping needles) and
      95.45% that they had been informed about the correct use of PPE. CONCLUSIONS: The
      lower percentage of injuries in students could be linked to good university
      training and to less risky procedures being performed. Re-capping needles remains
      one of the most dangerous manoeuvers practised. Ongoing training on the correct
      use of PPE is essential to train prepared and aware health professionals.

PMID- 25951869
TI  - [In memory of Giovanni Berlinguer (1924-2015): scientist and politician of
      health].

PMID- 25951865
TI  - [Prevention of accidental needle sticks before the Directive 2010/32/EU in a
      sample of Italian hospitals].
AB  - INTRODUCTION: Needlesticks and cuts are the most common occupational injuries in
      healthcare workers (HCWs). Directive 2010/32/EU defines principles and preventive
      interventions. OBJECTIVES: To assess, in hospitals participating in the Italian
      Study on Occupational Risk of HIV (SIROH) project, which are very active in
      prevention, the degree of application of the measures provided for by the
      Directive, prior to its incorporation into Italian law. METHODS: An open
      questionnaire covering the 9 focal points of the Directive, as a guide for a
      presentation at the SIROH meeting in 2013. RESULTS: Of 100 SIROH hospitals, 97%
      and 96% respectively provide specific information and education initiatives (54%
      and 73% of which expressly for new employees). All centres reinforce the ban on
      recapping, and 30 monitor its application by inspecting sharps containers; all
      hospitals place containers on mobile trolleys and 78 provide operating procedures
      for their replacement; all introduced at least one needlestick-prevention device
      (NPD; 4 on average, range 1-11), most frequently intravenous catheters (91%) and
      winged needles (87%), but 39% only in selected units; 14 centres implemented
      initiatives to eliminate unnecessary needles. Regarding hepatitis B, all centres
      screen and vaccinate HCWs but only 78% monitor their response: 89% of HCWs were
      immunized. Post-exposure management protocols, although based on the same
      rationale, differ significantly causing considerable differences in  costs.
      CONCLUSIONS: Most of the preventive interventions covered by the Directive were
      implemented in SIROH hospitals. It is necessary to invest in NPD availability and
      dissemination, elimination of unnecessary needles, and streamline post-exposure
      protocols. The situation in the remaining Italian facilities should be
      investigated.

PMID- 25951870
TI  - Obituary. Dr. Maths Berlin.

PMID- 25951873
TI  - Volumetric laser endomicroscopy in Barrett's esophagus: a feasibility study on
      histological correlation.
AB  - Volumetric laser endomicroscopy (VLE) is a novel balloon-based optical coherence
      tomography (OCT) imaging technique that may improve detection of early neoplasia
      in Barrett's esophagus (BE). Most OCT studies lack a direct correlation between
      histology and OCT images. The aim is to investigate the optimal approach for
      achieving one-to-one correlation of ex-vivo VLE images of endoscopic resection
      (ER) specimens with histology. BE patients with and without early neoplasia
      underwent ER after delineating areas with electrocoagulation markers (ECM). After
      ER, specimens underwent additional ex-vivo marking with several different markers
      (ink, pin, Gold Probe) followed by ex-vivo VLE scanning. ER specimens were
      carefully sectioned into tissue blocks guided by the markers. Histology and VLE
      slides were considered a match if >= 2 markers were visible on both modalities
      and mucosal patterns aside from these markers matched on both histology and VLE.
      From 16 ER specimens 120 tissue blocks were sectioned of which 23 contained
      multiple markers. Fourteen histology-VLE matches were identified. ECMs and ink
      markers proved to be the most effective combination for matching. The last 6/16
      ER specimens yielded 9/14 matches, demonstrating a learning curve due to
      methodological improvements in marker placement and tissue block sectioning. One
      to-one correlation of VLE and histology is complex but feasible. The groundwork
      laid in this study will provide high-quality histology-VLE correlations that will
      allow further research on VLE features of early neoplasia in BE. 

PMID- 25951872
TI  - En bloc resection for treatment of tumor-induced osteomalacia: a case
      presentation and a systematic review.
AB  - BACKGROUND: Tumor-induced osteomalacia (TIO) is a rare disorder, which is
      commonly found in craniofacial locations and in the extremities. To the best of
      our knowledge, only 16 cases have been described in the spine, and this is the
      first report to describe a case of patient with TIO in the thoracic spine
      combined with a mesenchymal hamartoma which had confused the therapeutic
      strategies to date. CASE DESCRIPTION: We report the case of a 60-year-old patient
      with hypophosphatemia and presented with limb weakness. Treating with phosphate
      did not correct the hypophosphatemia and an (111)In pentetreotide scintigraphy
      (octreotide scan) revealed an increased uptake at the right forearm. The tumor
      was resected totally, and the histopathology revealed a mesenchymal hamartoma,
      but we noticed that hypophosphatemia was not corrected after the tumor resection.
      Then a whole-body magnetic resonance imaging (WB-MRI) was performed and the
      results revealed tumorous tissues at the right T1 vertebral pedicle. The tumor
      was removed with an en bloc method, and the pathology showed phosphaturic
      mesenchymal tumor. Follow-up at 1 year after surgery revealed no recurrence, and
      the serum phosphorus level of the patient was normal. CONCLUSIONS: Tumor-induced
      osteomalacia is exceedingly rare with only 16 cases in spine published in the
      literature. It is difficult to find and leads to years of suffering debilitating
      complications. In this regard, the WB-MRI is a better method to locate the real
      tumor. Treating with phosphate can only relieve symptoms, and a complete surgical
      removal remains the gold standard treatment.

PMID- 25951871
TI  - Individualized medicine enabled by genomics in Saudi Arabia.
AB  - The biomedical research sector in Saudi Arabia has recently received special
      attention from the government, which is currently supporting research aimed at
      improving the understanding and treatment of common diseases afflicting Saudi
      Arabian society. To build capacity for research and training, a number of centres
      of excellence were established in different areas of the country. Among these, is
      the Centre of Excellence in Genomic Medicine Research (CEGMR) at King Abdulaziz
      University, Jeddah, with its internationally ranked and highly productive team
      performing translational research in the area of individualized medicine. Here,
      we present a panorama of the recent trends in different areas of biomedical
      research in Saudi Arabia drawing from our vision of where genomics will have
      maximal impact in the Kingdom of Saudi Arabia. We describe advances in a number
      of research areas including; congenital malformations, infertility, consanguinity
      and pre-implantation genetic diagnosis, cancer and genomic classifications in
      Saudi Arabia, epigenetic explanations of idiopathic disease, and pharmacogenomics
      and personalized medicine. We conclude that CEGMR will continue to play a pivotal
      role in advances in the field of genomics and research in this area is facing a
      number of challenges including generating high quality control data from Saudi
      population and policies for using these data need to comply with the
      international set up. 

PMID- 25951874
TI  - The effect of measurement position on brachial-ankle pulse wave velocity.
AB  - Arterial stiffness measurements are primarily used for the early detection of
      arteriosclerosis. Methods and devices that can easily measure arterial stiffness
      at home are in demand. We propose a simple method for measuring brachial-ankle
      pulse wave velocity (baPWV) at home using a reclining chair and investigate the
      effects of positioning on baPWV measurement. We measured baPWV in 50 healthy men
      (21-70 years) in seven different measurement positions, including the supine
      position, sitting, sitting with the knees flexed at 45 degrees , sitting with the
      knees flexed at 0 degrees , reclining at 37 degrees , reclining at 50 degrees ,
      and standing. BaPWV was significantly lower in the supine position (P < 0.01)
      than in the other positions. It was significantly higher in the sitting position
      (P < 0.01) than in the reclining position (37 degrees ). No changes in baPWV were
      seen changing the knee flexion angle alone while sitting. Strong correlations
      were also ob- served between baPWV in the supine position and that in other
      positions. We showed that baPWV in the supine position can be calcu- lated by
      making corrections to baPWV measured in the sitting position at a reclining
      angle. Utilizing this corrected value would allow easy measurement at home using
      a reclining chair. 

PMID- 25951875
TI  - Characterization of dopamine releasable and reserve pools in Drosophila larvae
      using ATP/P2X2 -mediated stimulation.
AB  - Dopaminergic signaling pathways are conserved between mammals and Drosophila, but
      the factors important for maintaining the functional pool of synaptic dopamine
      are not fully understood in Drosophila. In this study, we characterized the
      releasable and reserve dopamine pools in Drosophila larvae using ATP/P2X2 
      mediated stimulation. Dopamine release was stable with stimulations performed at
      least every 5 min but decayed with stimulations performed 2 min apart or less,
      indicating the replenishment of the releasable pool occurred on a time scale
      between 2 and 5 min. Dopamine synthesis or uptake was pharmacologically inhibited
      with 3-iodotyrosine and cocaine, respectively, to evaluate their contributions to
      maintain the releasable dopamine pool. We found that both synthesis and uptake
      were needed to maintain the releasable dopamine pool, with synthesis playing a
      major part in long-term replenishment and uptake being more important for short
      term replenishment. These effects of synthesis and uptake on different time
      scales in Drosophila are analogous to mammals. However, unlike in mammals,
      cocaine did not activate a reserve pool of dopamine in Drosophila when using P2X2
      stimulations. Our study shows that both synthesis and uptake replenish the
      releasable pool, providing a better understanding of dopamine regulation in
      Drosophila. The maintenance of the releasable dopamine pool was examined in
      Drosophila larva. Both synthesis and uptake were needed to maintain the
      releasable dopamine pool, with synthesis being most important on a longer time
      scale and uptake on a shorter time scale. Dopamine release was stimulated by
      applying ATP which activated P2X2 channels specifically expressed in dopaminergic
      neurons.

PMID- 25951876
TI  - Drug shortages: Implications for medical toxicology.
AB  - CONTEXT: Drug shortages have significantly increased over the past decade. There
      are limited data describing how shortages impact medical toxicology of drugs.
      OBJECTIVE: To characterize drug shortages affecting the management of poisoned
      patients. MATERIALS AND METHODS: Drug shortage data from January 2001 to December
      2013 were obtained from the University of Utah Drug Information Service. Shortage
      data for agents used to treat poisonings were analyzed. Information on drug type,
      formulation, reason for shortage, shortage duration, marketing, and whether the
      drug was available from a single source was collected. The availability of a
      substitute therapy and whether substitutes were in shortage during the study
      period were also investigated. RESULTS: Of 1,751 shortages, 141 (8.1%) impacted
      drugs used to treat poisoned patients, and as of December 2013, 21 (14.9%)
      remained unresolved. New toxicology shortages increased steadily from the mid
      2000s, reaching a high of 26 in 2011. Median shortage duration was 164 days
      (interquartile range: 76-434). Generic drugs were involved in 85.1% of shortages
      and 41.1% were single-source products. Parenteral formulations were often
      involved in shortages (89.4%). The most common medications in shortage were
      sedative/hypnotics (15.6%). An alternative agent was available for 121 (85.8%)
      drugs; however, 88 (72.7%) alternatives were also affected by shortages at some
      point during the study period. When present, the most common reasons reported
      were manufacturing delays (22.0%) and supply/demand issues (17.0%). Shortage
      reason was not reported for 48.2% of drugs. DISCUSSION: Toxicology drug shortages
      are becoming increasingly prevalent, which can result in both suboptimal
      treatment and medication errors from using less familiar alternatives.
      CONCLUSION: Drug shortages affected a substantial number of critical agents used
      in the management of poisoned patients. Shortages were often of long duration and
      for drugs without alternatives. Providers caring for poisoned patients should be
      aware of current shortages and implement mitigation strategies to safeguard
      patient care.

PMID- 25951877
TI  - Cardiac sodium channel blockade after an intentional ingestion of lacosamide,
      cyclobenzaprine, and levetiracetam: Case report.
AB  - CONTEXT: Lacosamide treats partial seizures by enhancing slow inactivation of
      voltage-gated sodium channels. The described cardiac toxicity of lacosamide in
      the literature to date includes atrioventricular blockade (PR prolongation),
      atrial flutter, atrial fibrillation, sinus pauses, ventricular tachycardia and a
      single cardiac arrest. We report a second case of cardiac arrest following an
      intentional lacosamide overdose. CASE DETAILS: A 16 year-old female with a
      seizure disorder was found unresponsive in pulseless ventricular tachycardia
      after intentionally ingesting 4.5 g (76 mg/kg) lacosamide, 120 mg (2 mg/kg)
      cyclobenzaprine and an unknown amount of levetiracetam. Exact time of ingestion
      was unknown. Her initial electrocardiogram (ECG) demonstrated sinus tachycardia
      at 139 beats per minute, QRS duration 112 ms, and terminal R-wave in lead aVR > 3
      mm. Despite treatment with 150 mEq of sodium bicarbonate, she had persistent EKG
      findings eight hours after presentation. Her serum lacosamide concentration nine
      hours after presentation was elevated at 22.8 MUg/mL, while serum cyclobenzaprine
      concentration was 16 ng/mL (therapeutic: 10-30 ng/mL), and serum levetiracetam
      concentration was 22.7 MUg/mL (therapeutic: 12-46 MUg/mL). On hospital day three,
      ECG demonstrated resolution of the terminal R-wave with QRS of 78 ms. The patient
      recovered without physical or neurologic sequelae. DISCUSSION: The patient's
      lacosamide, cyclobenzaprine and levetiracetam overdose was associated with QRS
      prolongation and terminal right axis deviation--suggesting sodium channel
      blockade as a likely etiology for her cardiac arrest. Cyclobenzaprine has
      potential for sodium channel blockade and ventricular dysrhythmias although
      cardiac toxicity due to cyclobenzaprine alone is rare. The combination of
      cyclobenzaprine with lacosamide may have resulted in cardiovascular collapse. In
      conclusion, overdose of lacosamide combined with therapeutic concentrations of
      sodium channel blocking xenobiotics may cause cardiac conduction delays and
      cardiac arrest.

PMID- 25951879
TI  - Molecular basis of inherited thrombocytopenias.
AB  - Inherited thrombocytopenias (IT) are a heterogeneous group of diseases caused by
      at least 20 different genes. At present, these genes account for approximately
      50% of cases, suggesting that novel genes have yet to be identified for a
      comprehensive understanding of platelet biogenesis defects. This review provides
      an update of ITs focusing on the molecular basis and potential pathogenic
      mechanisms affecting megakaryopoiesis and platelet production. 

PMID- 25951878
TI  - Individual variation and repeatability of methane production from dairy cows
      estimated by the CO2 method in automatic milking system.
AB  - The objectives of this study were to investigate the individual variation,
      repeatability and correlation of methane (CH4) production from dairy cows
      measured during 2 different years. A total of 21 dairy cows with an average BW of
      619 +/- 14.2 kg and average milk production of 29.1 +/- 6.5 kg/day (mean +/-
      s.d.) were used in the 1st year. During the 2nd year, the same cows were used
      with an average BW of 640 +/- 8.0 kg and average milk production of 33.4 +/- 6.0
      kg/day (mean +/- s.d.). The cows were housed in a loose housing system fitted
      with an automatic milking system (AMS). A total mixed ration was fed to the cows
      ad libitum in both years. In addition, they were offered concentrate in the AMS
      based on their daily milk yield. The CH4 and CO2 production levels of the cows
      were analysed using a Gasmet DX-4030. The estimated dry matter intake (EDMI) was
      19.8 +/- 0.96 and 23.1 +/- 0.78 (mean +/- s.d.), and the energy-corrected milk
      (ECM) production was 30.8 +/- 8.03 and 33.7 +/- 5.25 kg/day (mean +/- s.d.)
      during the 1st and 2nd year, respectively. The EDMI and ECM had a significant
      influence (P<0.001) on the CH4 (l/day) yield during both years. The daily CH4
      (l/day) production was significantly higher (P<0.05) during the 2nd year compared
      with the 1st year. The EDMI (described by the ECM) appeared to be the key factor
      in the variation of CH4 release. A correlation (r=0.54) of CH4 production was
      observed between the years. The CH4 (l/day) production was strongly correlated
      (r=0.70) between the 2 years with an adjusted ECM production (30 kg/day). The
      diurnal variation of CH4 (l/h) production showed significantly lower (P<0.05)
      emission during the night (0000 to 0800 h). The between-cows variation of CH4
      (l/day, l/kg EDMI and l/kg ECM) was lower compared with the within-cow variation
      for the 1st and 2nd years. The repeatability of CH4 production (l/day) was 0.51
      between 2 years. In conclusion, a higher EDMI (kg/day) followed by a higher ECM
      (kg/day) showed a higher CH4 production (l/day) in the 2nd year. The variations
      of CH4 (l/day) among the cows were lower than the within-cow variations. The CH4
      (l/day) production was highly repeatable and, with an adjusted ECM production,
      was correlated between the years.

PMID- 25951880
TI  - Chondroitin Sulfate Accelerates Trans-Golgi-to-Surface Transport of Proteoglycan
      Amyloid Precursor Protein.
AB  - The amyloid precursor protein (APP) is a membrane protein implicated in the
      pathogenesis of Alzheimer's disease. APP is a part-time proteoglycan, as splice
      variants lacking exon 15 are modified by a chondroitin sulfate glycosaminoglycan
      (GAG) chain. Investigating the effect of the GAG chain on the trafficking of APP
      in non-polarized cells, we found it to increase the steady-state surface-to
      intracellular distribution, to reduce the rate of endocytosis and to accelerate
      transport kinetics from the trans-Golgi network (TGN) to the plasma membrane.
      Deletion of the cytosolic domain resulted in delayed surface arrival of GAG-free
      APP, but did not affect the rapid export kinetics of the proteoglycan form.
      Protein-free GAG chains showed the same TGN-to-cell surface transport kinetics as
      proteoglycan APP. Endosome ablation experiments were performed to distinguish
      between indirect endosomal and direct pathways to the cell surface. Surprisingly,
      TGN-to-cell surface transport of both GAG-free and proteoglycan APP was found to
      be indirect via transferrin-positive endosomes. Our results show that GAGs act as
      alternative sorting determinants in cellular APP transport that are dominant over
      cytoplasmic signals and involve distinct sorting mechanisms. 

PMID- 25951882
TI  - Testosterone concentrations in female athletes and ballet dancers with menstrual
      disorders.
AB  - Menstrual disorders are common among female athletes and ballet dancers.
      Endocrine changes, such as high testosterone (HT) levels and high luteinizing
      hormone (LH)/follicle-stimulating hormone (FSH) ratios, may suggest functional
      ovarian hyperandrogenism which may induce such dysfunction. The aim of this study
      was therefore to evaluate endocrine status in female athletes and ballet dancers
      with menstrual disorders. Their nutritional status and dietary habits were
      analysed in relation to the testosterone levels. In a cross-sectional approach,
      31 female athletes (18.1 +/- 2.6 years) and 21 ballerinas (17.1 +/- 0.9) with
      menstrual disorders participated in the study. The levels of serum LH, FSH,
      progesterone (P), estradiol (E2), prolactin (PRL), thyroid-stimulating hormone,
      testosterone (T) and sex hormone-binding globulinwere measured to assess hormonal
      status. In addition, the free androgen index (FAI) was calculated. Nutritional
      status, total daily energy expenditure and nutritional habits were evaluated.
      Girls were assigned to one of the following groups: low testosterone (LT) level,
      normal testosterone level or HT level. There were significant differences between
      ballerinas and other female athletes in terms of testosterone levels, FAI, age at
      the beginning of training, length of training period and age at menarche. The PRL
      level was lowest in the LT group while the FAI index was highest in the HT group.
      Daily energy and carbohydrate intakes were significantly lower in the HT group. T
      levels in the study subjects were found to be associated with nutritional
      factors, energy availability, age at the beginning of training and frequency of
      training. This is the first report of HT levels being associated with the status
      of a female ballet dancer, the age of menarche and the length of the training
      history. Further research is necessary to confirm the results in a larger study
      group. 

PMID- 25951881
TI  - Disparities in the Utilization of Laparoscopic Surgery for Colon Cancer in Rural
      Nebraska: A Call for Placement and Training of Rural General Surgeons.
AB  - BACKGROUND: Advances in medical technology are changing surgical standards for
      colon cancer treatment. The laparoscopic colectomy is equivalent to the standard
      open colectomy while providing additional benefits. It is currently unknown what
      factors influence utilization of laparoscopic surgery in rural areas and if
      treatment disparities exist. The objectives of this study were to examine
      demographic and clinical characteristics associated with receiving laparoscopic
      colectomy and to examine the differences between rural and urban patients who
      received either procedure. METHODS: This study utilized a linked data set of
      Nebraska Cancer Registry and hospital discharge data on colon cancer patients
      diagnosed and treated in the entire state of Nebraska from 2008 to 2011 (N =
      1,062). Multiple logistic regression analysis was performed to identify
      predictors of receiving the laparoscopic treatment. RESULTS: Rural colon cancer
      patients were 40% less likely to receive laparoscopic colectomy compared to urban
      patients. Independent predictors of receiving laparoscopic colectomy were younger
      age (<60), urban residence, >=3 comorbidities, elective admission, smaller tumor
      size, and early stage at diagnosis. Additionally, rural patients varied
      demographically compared to urban patients. CONCLUSIONS: Laparoscopic surgery is
      becoming the new standard of treatment for colon cancer and important disparities
      exist for rural cancer patients in accessing the specialized treatment. As cancer
      treatment becomes more specialized, the importance of training and placement of
      general surgeons in rural communities must be a priority for health care planning
      and professional training institutions.

PMID- 25951885
TI  - The significance of caring.

PMID- 25951887
TI  - Resolving quandaries: basaloid adenoid cystic carcinoma or breast cylindroma? The
      role of massively parallel sequencing.
AB  - AIMS: The aims of this study were to perform a whole-exome sequencing analysis of
      a breast cylindroma and to investigate the role of molecular analyses in the
      differentiation between breast cylindroma, a benign tumour that displays MYB
      expression, and CYLD gene mutations, and its main differential diagnosis, the
      breast solid-basaloid adenoid cystic carcinoma, a malignant tumour that is
      characterized by the presence of the MYB-NFIB fusion gene and MYB overexpression.
      METHODS AND RESULTS: A 66-year-old female underwent quadrantectomy after an
      irregular dense shadow was discovered in the right breast at the screening
      mammogram. Histologically, the tumour displayed features suggestive of a solid
      basaloid variant of adenoid cystic carcinoma with a differential diagnosis of
      cylindroma. Fluorescence in situ hybridization, reverse transcription-polymerase
      chain reaction, immunohistochemistry and whole-exome sequencing revealed absence
      of the MYB-NFIB fusion gene, low levels of MYB protein expression and a clonal
      somatic CYLD splice site mutation associated with loss of heterozygosity of the
      wild-type allele. CONCLUSIONS: The results of the histological,
      immunohistochemical and molecular analyses were consistent with a diagnosis of
      breast cylindroma, providing a proof-of-principle that the integration of
      histopathological and molecular approaches can help to differentiate between a
      low-malignant potential and a benign breast tumour of triple-negative phenotype.

PMID- 25951889
TI  - Opinions and knowledge about organ donation and transplantation of residents of
      selected villages in Podlaskie Voivodeship.
AB  - BACKGROUND: In recent years, transplantation, a specific area of medicine, has
      achieved more and more support and acceptance among different nations around the
      world. However, there are still many ethical, moral, and legal barriers related
      to this form of treatment of end-stage organ failures. The aim of this study was
      to investigate the knowledge and opinions of rural residents about organ
      transplantation. MATERIAL AND METHODS: The research method is a diagnostic survey
      of 395 rural residents of selected villages of the region of Podlasie, located in
      north-east Poland. The research tool used to carry out the study was the authors'
      questionnaire. RESULTS: Organs procurement and transplantation from deceased
      donors are accepted by 72.6% of respondents. About 60% of the respondents would
      agree to organ donation for transplantation from the members of their family
      after death and 65.3% of the residents would be donors after their death. Half of
      the respondents (55.9%) believe that the final decision as to the donation of
      organs from a deceased person should be taken by the family. A positive attitude
      towards organ transplantation was expressed by 67.6% of respondents. CONCLUSIONS:
      Inhabitants of rural areas mostly agree with procurement of organs from the
      deceased and also from living donors. However, the enthusiasm and goodwill
      associated with the transplantation of organs after death diminished when the
      problem affects members of the family. Positive attitude about transplantation is
      related to age and level of the education.

PMID- 25951888
TI  - Lulling immunity, pain, and stress to sleep with cortistatin.
AB  - Cortistatin is a neuropeptide isolated from cortical brain regions, showing high
      structural homology and sharing many functions with somatostatin. However,
      cortistatin exerts unique functions in the central nervous and immune systems,
      including decreasing locomotor activity, inducing sleep-promoting effects, and
      deactivating inflammatory and T helper (TH )1/TH 17-driven responses in
      preclinical models of sepsis, arthritis, multiple sclerosis, and colitis. Besides
      its release by cortical and hippocampal interneurons, cortistatin is produced by
      macrophages, lymphocytes, and peripheral nociceptive neurons in response to
      inflammatory stimuli, supporting a physiological role of cortistatin in the
      immune and nociceptive systems. Cortistatin-deficient mice have been shown to
      have exacerbated nociceptive responses to neuropathic and inflammatory pain
      sensitization. However, a paradoxical effect has been observed in studies of
      immune disorders, in which, despite showing competent inflammatory/autoreactive
      responses, cortistatin-deficient mice were partially resistant to systemic
      autoimmunity and inflammation. This unexpected phenotype was associated with
      elevated circulating glucocorticoids and anxiety-like behavior. These findings
      support cortistatin as a novel multimodal therapeutic approach to treat
      autoimmunity and clinical pain and identify it as a key endogenous component of
      the neuroimmune system related to stress responses. 

PMID- 25951890
TI  - Vitreous State Characterization of Pharmaceutical Compounds Degrading upon
      Melting by Using Fast Scanning Calorimetry.
AB  - Fast scanning calorimetry, a technique mainly devoted to polymer
      characterization, is applied here for the first time to low molecular mass
      organic compounds that degrade upon melting, such as ascorbic acid and
      prednisolone. Due to the fast scan rates upon heating and cooling, the substances
      can be obtained in the molten state without degradation and then quenched into
      the glassy state. The hydrated form and the polymorphic Form 1 of prednisolone
      were investigated. It is shown that once the sesquihydrate dehydrates, a molten
      product is obtained. Depending on the heating rate, this molten phase may
      recrystallize or not into Form 1. 

PMID- 25951891
TI  - Adherent and Conformal Zn(S,O,OH) Thin Films by Rapid Chemical Bath Deposition
      with Hexamethylenetetramine Additive.
AB  - ZnS is a wide band gap semiconductor whose many applications, such as
      photovoltaic buffer layers, require uniform and continuous films down to several
      nanometers thick. Chemical bath deposition (CBD) is a simple, low-cost, and
      scalable technique to deposit such inorganic films. However, previous attempts at
      CBD of ZnS have often resulted in nodular noncontinuous films, slow growth rates
      at low pH, and high ratio of oxygen impurities at high pH. In this work, ZnS thin
      films were grown by adding hexamethylenetetramine (HMTA) to a conventional recipe
      that uses zinc sulfate, nitrilotriacetic acid trisodium salt, and thioacetamide.
      Dynamic bath characterization showed that HMTA helps the bath to maintain near
      neutral pH and also acts as a catalyst, which leads to fast nucleation and
      deposition rates, continuous films, and less oxygen impurities in the films.
      Films deposited on glass from HMTA-containing bath were uniform, continuous, and
      90 nm thick after 1 h, as opposed to films grown without HMTA that were ~3 times
      thinner and more nodular. On Cu2(Zn,Sn)Se4, films grown with HMTA were continuous
      within 10 min. The films have comparatively few oxygen impurities, with S/(S+O)
      atomic ratio of 88%, and high optical transmission of 98% at 360 nm. The
      Zn(S,O,OH) films exhibit excellent adhesion to glass and high resistivity, which
      make them ideal nucleation layers for other metal sulfides. Their promise as a
      nucleation layer was demonstrated with the deposition of thin, continuous Sb2S3
      overlayers. This novel HMTA chemistry enables rapid deposition of Zn(S,O,OH) thin
      films to serve as a nucleation layer, a photovoltaic buffer layer, or an
      extremely thin continuous coating for thin film applications. HMTA may also be
      applied in a similar manner for solution deposition of other metal chalcogenide
      and oxide thin films with superior properties.

PMID- 25951893
TI  - Selective actions of Lynx proteins on different nicotinic acetylcholine receptors
      in the locust, Locusta migratoria manilensis.
AB  - Nicotinic acetylcholine receptors (nAChRs) are major neurotransmitter receptors
      and targets of neonicotinoid insecticides in the insect nervous system. The full
      function of nAChRs is often dependent on associated proteins, such as chaperones,
      regulators and modulators. Here, three Lynx (Ly-6/neurotoxin) proteins, Loc
      lynx1, Loc-lynx2 and Loc-lynx3, were identified in the locust, Locusta migratoria
      manilensis. Co-expression with Lynx resulted in a dramatic increase in agonist
      evoked macroscopic currents on nAChRs Localpha1/beta2 and Localpha2/beta2 in
      Xenopus oocytes, but no changes in agonist sensitivity. Loc-lynx1 and Loc-lynx3
      only modulated nAChRs Localpha1/beta2 while Loc-lynx2 modulated Localpha2/beta2
      specifically. Meanwhile, Loc-lynx1 induced a more significant increase in
      currents evoked by imidacloprid and epibatidine than Loc-lynx3, and the effects
      of Loc-lynx1 on imidacloprid and epibatidine were significantly higher than those
      on acetylcholine. Among three lynx proteins, only Loc-lynx1 significantly
      increased [(3) H]epibatidine binding on Localpha1/beta2. The results indicated
      that Loc-lynx1 had different modulation patterns in nAChRs compared to Loc-lynx2
      and Loc-lynx3. Taken together, these findings indicated that three Lynx proteins
      were nAChR modulators and had selective activities in different nAChRs. Lynx
      proteins might display their selectivities from three aspects: nAChR subtypes,
      various agonists and different modulation patterns. Insect Lynx (Ly-6/neurotoxin)
      proteins act as the allosteric modulators on insect nicotinic acetylcholine
      receptors (nAChRs), the important targets of insecticides. We found that insect
      lynx proteins showed their selectivities from at least three aspects: nAChR
      subtypes, various agonists and different modulation patterns. 

PMID- 25951892
TI  - Molecular genetics of human primary microcephaly: an overview.
AB  - Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder
      that is characterised by microcephaly present at birth and non-progressive mental
      retardation. Microcephaly is the outcome of a smaller but architecturally normal
      brain; the cerebral cortex exhibits a significant decrease in size. MCPH is a
      neurogenic mitotic disorder, though affected patients demonstrate normal neuronal
      migration, neuronal apoptosis and neural function. Twelve MCPH loci (MCPH1
      MCPH12) have been mapped to date from various populations around the world and
      contain the following genes: Microcephalin, WDR62, CDK5RAP2, CASC5, ASPM, CENPJ,
      STIL, CEP135, CEP152, ZNF335, PHC1 and CDK6. It is predicted that MCPH gene
      mutations may lead to the disease phenotype due to a disturbed mitotic spindle
      orientation, premature chromosomal condensation, signalling response as a result
      of damaged DNA, microtubule dynamics, transcriptional control or a few other
      hidden centrosomal mechanisms that can regulate the number of neurons produced by
      neuronal precursor cells. Additional findings have further elucidated the
      microcephaly aetiology and pathophysiology, which has informed the clinical
      management of families suffering from MCPH. The provision of molecular diagnosis
      and genetic counselling may help to decrease the frequency of this disorder. 

PMID- 25951895
TI  - Type synthesis and preliminary design of devices supporting lower limb's
      rehabilitation.
AB  - PURPOSE: Based on the analysis of existing solutions, biomechanics of human lower
      limbs and anticipated applications, results of con- siderations concerning the
      necessary number of degrees of freedom for the designed device supporting
      rehabilitation of lower extremities are presented. An analysis was carried out in
      order to determine the innovative kinematic structure of the device, ensuring
      sufficient mobility and functionality while minimizing the number of degrees of
      freedom. METHODS: With the aid of appropriate formalised meth- ods, for instance,
      type synthesis, a complete variety of solutions for leg joints were obtained in
      the form of basic and kinematic schemes, having the potential to find application
      in devices supporting lower limb rehabilitation. RESULTS: A 3D model of ankle
      joint module was built in Autodesk Inventor System, then imported to Adams and
      assembled into a moving numerical model of a mechanism. Several conducted
      simulations resulted in finding the required maximum stroke of the cylinders.
      CONCLUSIONS: A comparison of the angular ranges of ankle joint and similar
      devices with the ones achieved by the designed device indicated a sufficient
      reserve allowing not only movements typical of gait, but approximately achieving
      the passive range of motion for the ankle joint.

PMID- 25951894
TI  - Biological and clinical outcomes in the elderly with left ventricular
      dysfunction: Are there differences between on-pump and off-pump coronary artery
      bypass grafting?
AB  - AIM: To compair biological and clinical outcomes after off-pump coronary artery
      bypass grafting (OPCABG) and conventional on-pump coronary artery bypass grafting
      (CCABG) in the elderly with left ventricular (LV) dysfunction. MATERIAL OF STUDY:
      We retrospectively reviewed 90 consecutive patients aged more than 75 years with
      preoperative left ventricular ejection fraction (LVEF) < 50% who underwent
      isolated coronary artery bypass grafting at our Institution between January 2000
      and July 2009. According to operative technique, patients were categorized in to
      the OPCABG group (39 patients) or in to the CCABG group (51 patients). We
      compared postoperative CK, CK-MB, troponin T serum levels and major adverse
      cardiac and cerebrovascular events (MACCE). RESULTS: The overall in-hospital
      mortality was 2% (2/90) and was similar in both groups (p=0.8336). Mean troponin
      T levels at 6,24,48 hours after operation were significantly lower in the OPCABG
      group (p=0.0001; p=0.0021; p=0.0070, respectively). Overall survival was 77.6% at
      10 years and no significant difference in MACCE was observed (p=0.3016).
      DISCUSSION: Our results show a lower incidence of myocardial injury in OPCABG
      group, but there aren't differences in term of MACCE in both groups. Recent
      studies have indicated the advantages of OPCABG in the elderly patients,
      reporting a reduction of postoperative morbidity and organ dysfunction. However
      these studies not analyzed the impact of LV dysfunction on early and late
      postoperative outcomes in high-risk patients. CONCLUSIONS: In the elderly with LV
      dysfunction, the OPCABG technique showed lower incidence of postoperative
      myocardial injury. However, at the follow-up, this does not reflect any
      significant differences in incidence of MACCE.

PMID- 25951896
TI  - Detection of serum melanoma-associated antigen D4 in patients with squamous cell
      carcinoma of the esophagus.
AB  - Despite improvements in surgical techniques, perioperative management, and
      multidisciplinary therapy, treatment outcomes of patients with esophageal
      squamous cell carcinoma (ESCC) remain poor. Therefore, development of novel
      molecular biomarkers, which either predict patient survival or become therapeutic
      targets, is urgently required. In the present study, to facilitate early
      detection of ESCC and predict its clinical course, we investigated the
      relationship of the serum level of melanoma-associated antigen (MAGE)-D4 to
      patients' clinicopathological characteristics. Using quantitative real-time
      reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent
      assays, we determined the levels of MAGE-D4 mRNA and protein in cell lysates and
      conditioned medium of cultures, respectively, of nine ESCC cell lines. Further,
      we determined MAGE-D4 levels in serum samples collected from 44 patients with
      ESCC who underwent radical esophagectomy without neoadjuvant therapy as well as
      from 40 healthy volunteers. Samples of conditioned medium and cell lysates
      contained comparable levels of MAGE-D4 that correlated closely with the levels of
      MAGE-D4 mRNA. Preoperative MAGE-D4 levels in the sera of 44 patients with ESCC,
      which varied from 0 to 2,354 pg/mL (314 +/- 505 pg/mL, mean +/- standard
      deviation), were significantly higher compared with those of healthy volunteers.
      By setting the cutoff at the highest value for healthy volunteers (50 pg/mL), the
      MAGE-D4-positive group of patients was more likely to have shorter disease
      specific and disease-free survival compared with those of the MAGE-D4-negative
      group, although the differences were not statistically significant. Our results
      indicate that the elevation of preoperative serum MAGE-D4 levels in some patients
      with ESCC was possibly caused by excess production of MAGE-D4 by tumor cells
      followed by its release into the circulation. Clinical implications of serum MAGE
      D4 levels should be validated in a large population of patients with ESCC. 

PMID- 25951897
TI  - Tissue expression and predicted protein structures of the bovine ANGPTL3 and
      association of novel SNPs with growth and meat quality traits.
AB  - Angiopoietin-like protein 3 (ANGPTL3) is a secreted protein that regulates lipid,
      glucose and energy metabolism. This study was conducted to better understand the
      effect of ANGPTL3 on important economic traits in cattle. First, transcript
      profiles for ANGPTL3 were measured in nine different Jiaxian cattle tissues.
      Second, polymorphisms were identified in the complete coding region and promoter
      region of the bovine ANGPTL3 gene in 707 cattle samples. Finally, an association
      study was carried out utilizing these single nucleotide polymorphisms (SNPs) to
      determine the effect of these SNPs on the growth and meat quality traits.
      Quantitative real-time PCR analysis showed that ANGPTL3 was mainly expressed in
      the liver. The promoter of the bovine ANGPTL3 contained several putative
      transcription factor binding sites (SF1, HNF-1, LXRalpha, NFkappabeta, HNF-3 and
      C/EBP). In total, four SNPs of the bovine ANGPTL3 gene were identified by direct
      sequencing. SNP1 (rs469906272: g.-38T>C) was identified in the promoter, SNP2
      (rs451104723:g.104A>T) and SNP3 (rs482516226: g.509A>G) were identified in exon
      1, and SNP4 (rs477165942: g.8661T>C) was identified in exon 6. Changes in
      predicted protein structures due to non-synonymous SNPs were analyzed. Haplotype
      frequencies and linkage disequilibrium were also investigated. Analysis of four
      SNPs in cattle from different native Chinese breeds (Nanyang (NY) and Jiaxian
      (JX)) and commercial breeds (Angus (AG), Hereford (HF), Limousin (LM), Luxi (LX),
      Simmental (ST) and Jinnan (JN)) revealed a significant association with growth
      traits (including: BW and hipbone width) and meat quality traits (including:
      Warner-Bratzler shear force and ribeye area). Therefore, implementation of these
      four mutations in selection indices in the beef industry may be beneficial in
      selecting individuals with superior growth and meat quality traits. 

PMID- 25951899
TI  - Does therapeutic use of tapentadol cause false-positive urine screens for
      methadone or opiates?

PMID- 25951900
TI  - Determination of biological removal of recalcitrant organic contaminants in coal
      gasification waste water.
AB  - Coal gasification waste water treatment needed a sustainable and affordable plan
      to eliminate the organic contaminants in order to lower the potential
      environmental and human health risk. In this paper, a laboratory-scale anaerobic
      aerobic intermittent system carried out 66 operational cycles together for the
      treatment of coal gasification waste water and the removal capacity of each
      organic pollutant. Contaminants included phenols, carboxylic acids, long-chain
      hydrocarbons, and heterocyclic compounds, wherein the relative content of phenol
      is up to 57.86%. The long-term removal of 77 organic contaminants was evaluated
      at different hydraulic retention time (anaerobic24 h + aerobic48 h and
      anaerobic48 h +aerobic48 h). Contaminant removal ranged from no measurable
      removal to near-complete removal with effluent concentrations below the detection
      limit. Contaminant removals followed one of four trends: steady-state removal
      throughout, increasing removal to steady state (acclimation), decreasing removal,
      and no removal. Organic degradation and transformation in the reaction were
      analysed by gas chromatography/mass spectrometry technology. 

PMID- 25951898
TI  - Why underserved patients do not consult their general practitioner for
      depression: results of a qualitative and a quantitative survey at a free
      outpatient clinic in Paris, France.
AB  - BACKGROUND: The prevalence of depression in the general population is 5 to 10%
      but can exceed 50% in the most socially vulnerable populations. The perceptions
      of this disease are widely described in the literature, but no research has been
      carried out in France to explain the reasons for not consulting a general
      practitioner during a depressive episode, particularly in people in the most
      precarious situations. The objective of this study was to describe the reasons
      for not seeking primary care during a depressive episode in a socially vulnerable
      population. METHODS: An exploratory sequential design with a preliminary
      qualitative study using a phenomenological approach. Subsequently, themes that
      emerged from the qualitative analysis were used in a questionnaire administered
      in a cross-sectional observational study at a free outpatient clinic in Paris in
      2010. Lastly, a logistic regression analysis was performed. RESULTS: The
      qualitative analysis revealed four aspects that explain the non-consulting of a
      general practitioner during a depressive episode: the negative perception of
      treatment, the negative perception of the disease, the importance of the social
      environment, and the doctor-patient relationship. The quantitative analysis
      showed that close to 60% of the patients who visited the free clinic were
      depressed and that only half of them had talked with a care provider. The results
      of the statistical analysis are in line with those of the qualitative analysis,
      since the most common reasons for not seeing a general practitioner were the
      negative perception of the disease (especially among the men and foreigners) and
      its treatments (more often among the men and French nationals). CONCLUSIONS:
      Close to 50% of the depressed individuals did not seek primary care during a
      depressive episode, and close to 80% of them would have liked their mental health
      to be discussed more often by a health professional. Better information on
      depression and its treatments, and more-systematic screening by primary care
      personnel would improve the treatment of depressed patients, especially those in
      the most precarious situations.

PMID- 25951901
TI  - Considerations for Systemic Anticoagulation in ESRD.
AB  - In the setting of end-stage kidney disease, the incidence and risk for thrombotic
      events are increased and use of anticoagulants is common. The incidence of
      bleeding, however, is also a frequent issue and creates additional challenges in
      the management of anticoagulation therapy. Patients with end-stage renal disease
      are typically excluded from large clinical trials exploring the use of
      anticoagulants, which limits our knowledge of optimal management approaches.
      Furthermore, varying degrees of renal failure in addition to conditions that
      alter the pharmacokinetics of various anticoagulants or pharmacodynamic response
      may warrant alternative approaches to dosing. This review will explore systemic
      chronic anticoagulation therapy in the setting of chronic kidney disease where
      hemodialysis is required. Agents discussed include vitamin K antagonists, low
      molecular-weight heparins, fondaparinux, oral factor Xa antagonists, and direct
      thrombin inhibitors. Clinical challenges, approaches to dosing regimens, and
      tools for measuring responses and reversal will be explored. 

PMID- 25951903
TI  - let-7b and let-7c are determinants of intrinsic chemoresistance in renal cell
      carcinoma.
AB  - BACKGROUND: Renal cell carcinoma (RCC) is characterized by inherent resistance to
      chemotherapy. Earlier studies demonstrated that microRNAs (miRNAs) might be
      involved in the chemosensitivity of cancers. MicroRNA let-7, a putative tumor
      suppressor, is dysregulated in many cancers. Our study aims to investigate the
      exact role of let-7 in chemotherapy sensitivity of 5-fluorouracil (5-FU) in RCC.
      METHODS: The clinical significance of let-7b and let-7c expression in surgically
      resected specimens was assessed by qRT-PCR. Cell proliferation assay and colony
      formation assay were used to assess the survival of 786-O cells treated with let
      7b or let-7c combined with 5-FU. Western blot was used to detect the expression
      of Akt2 and caspase-7. Luciferase assay was used to detect the direct binding of
      let-7b and let-7c to the 3'-untranslated region (UTR) of Akt2. RESULTS:
      Expression of let-7b and let-7c was significantly decreased in 32 paired clear
      cell renal cell carcinoma tissue specimens and the dysregulation of let-7b was
      associated with pathological grade. Transfection of let-7b or let-7c combined
      with 5-FU inhibited proliferation and potentiated the antitumor efficacies of 5
      FU at tolerated concentration. let-7b and let-7c suppressed the luciferase
      activity of reporter plasmid containing the 3'-UTR of Akt2. Overexpression of let
      7b and let-7c reduced Akt2 expression, and Akt2 inhibition enhanced the
      sensitivity to 5-FU by affecting apoptotic pathway. CONCLUSIONS: Expression of
      let-7b and let-7c was frequently decreased in clear cell renal cell carcinoma
      tissues. The dysregulation of let-7b and let-7c may be involved in
      chemoresistance of RCC cells to 5-FU by down-regulating Akt2.

PMID- 25951904
TI  - A clinical approach to diagnose patients with localized telangiectasia.
AB  - Telangiectasia, or dilated blood vessels, may represent a benign condition or a
      marker of a much more serious internal or cutaneous malignancy (e.g., mycosis
      fungoides). They can be generalized or localized in distribution. 'Localized
      telangiectasia? can be macular or papular. Macular ones can be further divided
      into two major categories: primary and secondary. They can occur on their own
      (primary), after skin injury (e.g., sun damage, post-radiation therapy, after
      prolonged topical steroid application), or may arise due to an underlying
      condition (secondary). While telangiectases can spring from a multitude of
      possible causes, the location of the lesions, in combination with a careful
      history and exmination, often helps in elucidating the correct diagnosis. A
      patient with localized telangiectasia as a manifestation of malignancy may be
      difficult to diagnose, however the diagnosis is one of exclusion, and a thorough
      evaluation should be performed before diagnosing this condition. This article
      reviews possible conditions to consider in these patients and suggests an
      approach to their evaluation.

PMID- 25951905
TI  - Music enhances verbal episodic memory in Alzheimer's disease.
AB  - INTRODUCTION: Although previous studies suggest that music may facilitate verbal
      learning in a healthy population, such a mnemonic effect has seldom been
      investigated in Alzheimer's disease (AD). Moreover, memorization of texts was
      generally compared when either sung or spoken. In the present study, it was
      examined whether the benefit observed on verbal learning was specific to music or
      whether an associative context binding items together led to similar benefits,
      regardless of the nature of the association. METHOD: Twelve patients with mild AD
      and 15 healthy controls learned texts presented with either a musical (sung) or a
      nonmusical association (spoken associated to a silent movie sequence) or without
      association (spoken alone). Immediate and delayed (after a 5-min delay) recall
      was measured. RESULTS: Main results showed that (a) sung texts were better
      remembered than spoken texts, both immediately and after a retention delay, for
      both groups; (b) the musical benefit was robust, being observed in most AD
      patients; (c) the nonmusical association may also facilitate verbal learning but
      to a lesser extent. CONCLUSIONS: A musical association during the encoding stage
      facilitates learning and retention in AD. Furthermore, this advantage seemed
      quite specific to music. The results are discussed with respect to the clinical
      applications in AD; theoretical implications are highlighted to explain the power
      of music as a mnemonic technique.

PMID- 25951906
TI  - Impact of QTL properties on the accuracy of multi-breed genomic prediction.
AB  - BACKGROUND: Although simulation studies show that combining multiple breeds in
      one reference population increases accuracy of genomic prediction, this is not
      always confirmed in empirical studies. This discrepancy might be due to the
      assumptions on quantitative trait loci (QTL) properties applied in simulation
      studies, including number of QTL, spectrum of QTL allele frequencies across
      breeds, and distribution of allele substitution effects. We investigated the
      effects of QTL properties and of including a random across- and within-breed
      animal effect in a genomic best linear unbiased prediction (GBLUP) model on
      accuracy of multi-breed genomic prediction using genotypes of Holstein-Friesian
      and Jersey cows. METHODS: Genotypes of three classes of variants obtained from
      whole-genome sequence data, with moderately low, very low or extremely low
      average minor allele frequencies (MAF), were imputed in 3000 Holstein-Friesian
      and 3000 Jersey cows that had real high-density genotypes. Phenotypes of traits
      controlled by QTL with different properties were simulated by sampling 100 or
      1000 QTL from one class of variants and their allele substitution effects either
      randomly from a gamma distribution, or computed such that each QTL explained the
      same variance, i.e. rare alleles had a large effect. Genomic breeding values for
      1000 selection candidates per breed were estimated using GBLUP modelsincluding a
      random across- and a within-breed animal effect. RESULTS: For all three classes
      of QTL allele frequency spectra, accuracies of genomic prediction were not
      affected by the addition of 2000 individuals of the other breed to a reference
      population of the same breed as the selection candidates. Accuracies of both
      single- and multi-breed genomic prediction decreased as MAF of QTL decreased,
      especially when rare alleles had a large effect. Accuracies of genomic prediction
      were similar for the models with and without a random within-breed animal effect,
      probably because of insufficient power to separate across- and within-breed
      animal effects. CONCLUSIONS: Accuracy of both single- and multi-breed genomic
      prediction depends on the properties of the QTL that underlie the trait. As QTL
      MAF decreased, accuracy decreased, especially when rare alleles had a large
      effect. This demonstrates that QTL properties are key parameters that determine
      the accuracy of genomic prediction.

PMID- 25951902
TI  - Synaptic Cytoskeletal Plasticity in the Prefrontal Cortex Following
      Psychostimulant Exposure.
AB  - Addiction is characterized by maladaptive decision-making, a loss of control over
      drug consumption and habit-like drug seeking despite adverse consequences. These
      cognitive changes may reflect the effects of drugs of abuse on prefrontal
      cortical neurobiology. Here, we review evidence that amphetamine and cocaine
      fundamentally remodel the structure of excitatory neurons in the prefrontal
      cortex. We summarize evidence in particular that these psychostimulants have
      opposing effects in the medial and orbital prefrontal cortices ('mPFC' and
      'oPFC', respectively). For example, amphetamine and cocaine increase dendrite
      length and spine density in the mPFC, while dendrites are impoverished and
      dendritic spines are eliminated in the oPFC. We will discuss evidence that
      certain cytoskeletal regulatory proteins expressed in the oPFC and implicated in
      postnatal (adolescent) neural development also regulate behavioral sensitivity to
      cocaine. These findings potentially open a window of opportunity for the
      identification of novel pharmacotherapeutic targets in the treatment of drug
      abuse disorders in adults, as well as in drug-vulnerable adolescent populations.
      Finally, we will discuss the behavioral implications of drug-related dendritic
      spine elimination in the oPFC, with regard to reversal learning tasks and tasks
      that assess the development of reward-seeking habits, both used to model aspects
      of addiction in rodents. 

PMID- 25951908
TI  - P450s and UGTs: Key Players in the Structural Diversity of Triterpenoid Saponins.
AB  - The recent spread of next-generation sequencing techniques has facilitated
      transcriptome analyses of non-model plants. As a result, many of the genes
      encoding enzymes related to the production of specialized metabolites have been
      identified. Compounds derived from 2,3-oxidosqualene (the common precursor of
      sterols, steroids and triterpenoids), a linear compound of 30 carbon atoms
      produced through the mevalonate pathway, are called triterpenes. These include
      essential sterols, which are structural components of biomembranes; steroids such
      as the plant hormones, brassinolides and the toxin in potatoes, solanine; as well
      as the structurally diverse triterpenoids. Triterpenoids containing one or more
      sugar moieties attached to triterpenoid aglycones are called triterpenoid
      saponins. Triterpenoid saponins have been shown to have various medicinal
      properties, such as anti-inflammatory, anticancerogenic and antiviral effects.
      This review summarizes the recent progress in gene discovery and elucidates the
      biochemical functions of biosynthetic enzymes in triterpenoid saponin
      biosynthesis. Special focus is placed on key players in generating the structural
      diversity of triterpenoid saponins, cytochrome P450 monooxygenases (P450s) and
      the UDP-dependent glycosyltransferases (UGTs). Perspectives on further gene
      discovery and the use of biosynthetic genes for the microbial production of plant
      derived triterpenoid saponins are also discussed. 

PMID- 25951907
TI  - Results of a cluster randomised controlled trial to reduce risky use of alcohol,
      alcohol-related HIV risks and improve help-seeking behaviour among safety and
      security employees in the Western Cape, South Africa.
AB  - OBJECTIVE: To test the effectiveness of a programme aimed at reducing the risky
      use of alcohol and alcohol-related HIV risk and increase help-seeking behaviour
      among a sample of municipal employees in the Western Cape Province, South Africa.
      METHODS: A clustered randomised controlled trial was conducted in 2011-2012 among
      325 employees. The eight hour intervention, Team Awareness (TA), addressing
      behavioural risk among employees was administered to 168 employees in the
      intervention arm and the 157 employees in the control arm who received a one-hour
      wellness talk. RESULTS: The results show that TA had the greatest impact on risky
      drinking practices and hangover effects. There was a significant group * time
      interaction (F (1, 117) = 25.16, p<0.0001) with participants in the intervention
      condition reducing number of days on which they engaged in binge drinking. There
      was also a significant time effect with participants in the intervention
      condition reducing the likelihood of going to work with a hangover (F (1,117) =
      4.10, p=0.045). No reduction in HIV-related risk behaviours were found.
      CONCLUSIONS: This intervention study was able to demonstrate a modest but
      significant reduction in risky drinking practices and hangover effects. This
      provides encouraging evidence for the effectiveness of interventions that address
      risky use of alcohol among employed persons, further providing a launch pad for
      strengthening and replicating future RCT studies on workplace prevention,
      especially in developing country settings. CLINICAL TRIAL REGISTRATION NUMBER:
      Pan-African Control Trial Registry (201301000458308) .

PMID- 25951909
TI  - Rare cause of trigeminal neuralgia: Meckel's cave meningocele.
AB  - The most common etiology of classic trigeminal neuralgia is vascular compression.
      However, other causes must be excluded. It is very unlikely that a meningocele
      presents with symptomatic trigeminal neuralgia. We present a rare case of a
      patient presenting with left trigeminal neuralgia. Thin-slice CT and MRI showed a
      transclival Meckel's cave meningocele. The patient underwent endoscopic repair of
      the meningocele, which resulted in complete resolution of her symptoms. Meckel's
      cave meningocele or encephalocele should be considered among the differential
      diagnoses of trigeminal neuralgia. Meningocele repair should be suggested as the
      first treatment option in this rare situation. 

PMID- 25951910
TI  - Rapid Learning in a Children's Museum via Analogical Comparison.
AB  - We tested whether analogical training could help children learn a key principle
      of elementary engineering-namely, the use of a diagonal brace to stabilize a
      structure. The context for this learning was a construction activity at the
      Chicago Children's Museum, in which children and their families build a model
      skyscraper together. The results indicate that even a single brief analogical
      comparison can confer insight. The results also reveal conditions that support
      analogical learning. 

PMID- 25951911
TI  - Two new defective distributions based on the Marshall-Olkin extension.
AB  - The presence of immune elements (generating a fraction of cure) in survival data
      is common. These cases are usually modeled by the standard mixture model. Here,
      we use an alternative approach based on defective distributions. Defective
      distributions are characterized by having density functions that integrate to
      values less than 1, when the domain of their parameters is different from the
      usual one. We use the Marshall-Olkin class of distributions to generalize two
      existing defective distributions, therefore generating two new defective
      distributions. We illustrate the distributions using three real data sets.

PMID- 25951913
TI  - Anaphylaxis to galacto-oligosaccharides--an evaluation in an atopic population in
      Singapore.
AB  - Anaphylaxis to galacto-oligosaccharides (GOS), a prebiotic, has been described in
      atopic patients following its supplementation in commercial milk formula in South
      East Asia. The epidemiology of this usual allergy to a carbohydrate is unknown.
      This study evaluated the prevalence of allergy to two formulations of commercial
      GOS, VivinalTM GOS (vGOS) and OligomateTM , in an atopic cohort. Atopic subjects
      (n = 487) from two specialist allergy clinics were surveyed via structured
      questionnaire and underwent skin prick tests to GOS. Subjects with positive skin
      prick tests to GOS (n = 30, 6.2%) underwent basophil activation tests, and a
      subset (n = 13) underwent oral challenge tests to both formulations of GOS. Six
      subjects had positive challenges to vGOS; and none to Oligomate. By extrapolating
      the BAT and oral challenge results, the prevalence of allergy to vGOS is
      estimated at up to 3.5% (95% CI 2.2-5.5%) of our atopic population. Our findings
      show that GOS allergy may be common amongst atopics in Singapore.

PMID- 25951912
TI  - Comparison of Airway and Systemic Malondialdehyde Levels for Assessment of
      Oxidative Stress in Cystic Fibrosis.
AB  - INTRODUCTION: Oxidative stress plays a pivotal role in the pathogenesis of cystic
      fibrosis (CF). In this study, airway and systemic oxidative stress was
      investigated in CF using malondialdehyde (MDA), an established by-product of
      polyunsaturated fatty acid peroxidation. METHODS: Exhaled breath condensate
      (EBC), sputum, and plasma were collected from 40 stable CF patients during
      routine clinical visits and from 25 healthy controls. MDA was measured by high
      performance liquid chromatography. RESULTS: MDA levels in sputum (279.8 +/- 14.7
      vs. 92.7 +/- 9.2 nmol/L, p < 0.0001), EBC (139.9 +/- 6.7 vs. 71.5 +/- 4.3 nmol/L,
      p < 0.0001), and plasma (176.1 +/- 15.9 vs. 129.6 +/- 12.9 nmol/L, p < 0.05) were
      increased in patients with CF compared to healthy controls. MDA measurement in
      sputum [area under receiver operating characteristic curve (AUC): 0.977, p <
      0.0001] or EBC (AUC: 0.94, p < 0.0001) discriminated between patients and
      controls with greater accuracy than in plasma (AUC: 0.677, p < 0.05). Sputum and
      EBC MDA levels were elevated in patients with severe pulmonary dysfunction
      [forced expiratory volume in 1 s (FEV1) <50 % predicted] compared to those with
      mild-to-moderate functional impairment (FEV1 >=50 % predicted) (p < 0.05). MDA
      concentrations in CF patients colonized either with Pseudomonas aeruginosa or
      with other bacteria were similar (p = NS). The intra- and inter-assay
      repeatabilities of MDA measurements was similar in all the three types of
      samples, while the between-visit variability was higher in plasma. CONCLUSIONS:
      MDA is a potential new airway marker of oxidative stress in patients with CF.
      Sputum MDA differentiates best between patients and healthy subjects.

PMID- 25951914
TI  - Strain and interface effects in a novel bismuth-based self-assembled supercell
      structure.
AB  - Bi2FeMnO6 (BFMO) thin films with both conventional pseudocubic structure and
      novel supercell structure have been grown on SrTiO3 (001) substrates with
      different thicknesses of CeO2 buffer layers (ranging from 6.7 to 50.0 nm) using
      pulsed laser deposition. The correlation between the thickness of the CeO2 buffer
      layer and the structure of the BFMO films shows that the CeO2 buffer layer, as
      thin as 6.7 nm, is sufficient in triggering the novel BFMO supercell structure.
      This may be ascribed to the interfacial strain between the BFMO supercell
      structure and the CeO2 buffer layer which also serves as a seed layer. The buffer
      layer thickness is found to be critical to control the microstructure and
      magnetism of the formed BFMO supercell structures. Thin seed layers can produce a
      smoother interface between the BFMO film and the CeO2 buffer layer, and therefore
      better ferrimagnetic properties. Our results have demonstrated that strain and
      interface could be utilized to generate novel thin film structures and to tune
      the functionalities of thin films. 

PMID- 25951915
TI  - Clinical impact of quantitative left atrial vortex flow analysis in patients with
      atrial fibrillation: a comparison with invasive left atrial voltage mapping.
AB  - Recently, left atrial (LA) vortex flow analysis using contrast transesophageal
      echocardiography (TEE) has been shown to be feasible and has demonstrated
      significant differences in vortex flow morphology and pulsatility between normal
      subjects and patients with atrial fibrillation (AF). However, the relationship
      between LA vortex flow and electrophysiological properties and the clinical
      significance of LA vortex flow are unknown. The aims of this study were (1) to
      compare LA vortex flow parameters with LA voltage and (2) to assess the
      predictive value of LA vortex flow parameters for the recurrence of AF after
      radiofrequency catheter ablation (RFCA). Thirty-nine patients with symptomatic
      non-valvular AF underwent contrast TEE before undergoing RFCA for AF.
      Quantitative LA vortex flow parameters were analyzed by Omega flow (Siemens
      Medical Solution, Mountain View, CA, USA). The morphology and pulsatility of LA
      vortex flow were compared with electrophysiologic parameters that were measured
      invasively. Hemodynamic, electrophysiological, and vortex flow parameters were
      compared between patients with and without early recurrence of AF after RFCA.
      Morphologic parameters, including LA vortex depth, length, width, and sphericity
      index were not associated with LA voltage or hemodynamic parameters. The relative
      strength (RS), which represents the pulsatility power of LA, was positively
      correlated with LA voltage (R = 0.53, p = 0.01) and LA appendage flow velocity (R
      = 0.73, p < 0.001) and negatively correlated with LA volume index (R = -0.56, p <
      0.001). Patients with recurrent AF after RFCA showed significantly lower RS (1.7
      +/- 0.2 vs 1.9 +/- 0.4, p = 0.048) and LA voltage (0.9 +/- 0.7 vs 1.7 +/- 0.8, p
      = 0.004) than patients without AF recurrence. In the relatively small LA
      dimension group (LA volume index <= 33 ml/m(2)), RS was significantly lower (2.1
      +/- 0.3 vs 1.7 +/- 0.1, p = 0.029) in patients with the recurrent AF.
      Quantitative LA vortex flow analysis, especially RS, correlated well with LA
      voltage. Decreased pulsatility strength in the LA was associated with recurrent
      AF. LA vortex may have incremental value in predicting the recurrence of AF.

PMID- 25951916
TI  - MRI monitoring of function, perfusion and viability in microembolized moderately
      ischemic myocardium.
AB  - Assessment of microembolization after coronary interventions is clinically
      challenging, thus we longitudinally investigated microemboli effects on
      moderately ischemic myocardium using MRI and histopathology. Twenty-four pigs
      (8/group) were divided into: group I (no intervention), group II (45 min LAD
      occlusion) and group III (45 min LAD occlusion with microembolization). Cine,
      perfusion and delayed contrast enhanced MRI (DE-MRI), using 1.5T MRI, were used
      for assessment at 3 days and 5 weeks. Triphenyltetrazolium-chloride (TTC) and
      Masson-trichrome were used as gold standard references for macro and microscopic
      quantification of myocardial infarction (MI). Cine MRI showed differential
      increase in end systolic volume (1.3 +/- 0.08 ml/kg group II and 1.6 +/- 0.1
      ml/kg group III) and decrease in ejection fraction (45 +/- 2 and 36 +/- 2%,
      respectively) compared with controls at 3 days (2.1 +/- 0.1 ml ESV and 50 +/- 1%
      EF, P < 0.05). At 5 weeks group III, but not II, showed persistent perfusion
      deficits, wall thinning in the LAD territory and compensatory hypertrophy in
      remote myocardium. DE-MRI MI at 3 days was significantly smaller in group II (3.3
      +/- 2.2 g) than III (9.8 +/- 0.6 g), at 5 weeks, MI were smaller by 60% (1.3 +/-
      0.9 g) and 22% (7.7 +/- 0.5 g), respectively. TTC MI was similar to DE-MRI in
      group II (1.6 +/- 1.0 g) and III (9.2 +/- 1.6 g), but not microscopy (2.8 +/- 0.4
      and 10.5 +/- 1.5 g, respectively). The effects of moderate ischemia with and
      without microembolization on myocardium could be differentiated using multiple
      MRI sequences. MRI demonstrated that microemboli in moderately ischemic
      myocardium, but not solely ischemia, prolonged ventricular dysfunction, created
      perfusion deficits, poor infarct resorption and enhanced compensatory
      hypertrophy, while moderate ischemia alone caused minor LV changes.

PMID- 25951917
TI  - Incidence of Running-Related Injuries Per 1000 h of running in Different Types of
      Runners: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: No systematic review has identified the incidence of running-related
      injuries per 1000 h of running in different types of runners. OBJECTIVE: The
      purpose of the present review was to systematically search the literature for the
      incidence of running-related injuries per 1000 h of running in different types of
      runners, and to include the data in meta-analyses. DATA SOURCES: A search of the
      PubMed, Scopus, SPORTDiscus, PEDro and Web of Science databases was conducted.
      STUDY SELECTION: Titles, abstracts, and full-text articles were screened by two
      blinded reviewers to identify prospective cohort studies and randomized
      controlled trials reporting the incidence of running-related injuries in novice
      runners, recreational runners, ultra-marathon runners, and track and field
      athletes. STUDY APPRAISAL AND SYNTHESIS METHODS: Data were extracted from all
      studies and comprised for further analysis. An adapted scale was applied to
      assess the risk of bias. RESULTS: After screening 815 abstracts, 13 original
      articles were included in the main analysis. Running-related injuries per 1000 h
      of running ranged from a minimum of 2.5 in a study of long-distance track and
      field athletes to a maximum of 33.0 in a study of novice runners. The meta
      analyses revealed a weighted injury incidence of 17.8 (95% confidence interval
      [CI] 16.7-19.1) in novice runners and 7.7 (95% CI 6.9-8.7) in recreational
      runners. LIMITATIONS: Heterogeneity in definitions of injury, definition of type
      of runner, and outcome measures in the included full-text articles challenged
      comparison across studies. CONCLUSION: Novice runners seem to face a
      significantly greater risk of injury per 1000 h of running than recreational
      runners.

PMID- 25951918
TI  - Toward an Understanding of the Oxidation Process of Methionine Enkephalin: A
      Combined Electrochemistry, Quantum Chemistry and Quantum Chemical Topology
      Analysis.
AB  - Recent experimental results about the oxidation of methionine enkephalin by .OH
      radicals indicated an intramolecular electron transfer between the C-terminal
      methionine radical cation and the tyrosine N-terminus too fast to be observed. We
      have investigated the thermodynamic possibility of this intramolecular electron
      transfer by calculating the one-electron redox potentials of both residues for
      several conformations of the peptide, extracted from the experimental data of the
      Protein Data Bank (1PLW). Using a QM/MM approach, we show that the redox
      potential of the Met(*+)/Met couple is higher than that of the TyrOH(*+)/TyrOH
      one (tyrosine is denoted as TyrOH) for all conformations. The intramolecular
      electron transfer between both residues (from TyrOH to Met(*+)) is thus always
      thermodynamically allowed. Previously, we had performed topological studies on
      the intramolecular electron transfer which predicted this charge transfer. A
      study by cyclic voltammetry pointed out that the wave belonging to methionine is
      not present when methionine enkephalin is oxidized and only the direct
      involvement of the tyrosine residue is observed. 

PMID- 25951919
TI  - An intracellular domain with a novel sequence regulates cell surface expression
      and synaptic clustering of leucine-rich repeat transmembrane proteins in
      hippocampal neurons.
AB  - Leucine-rich repeat transmembrane proteins (LRRTMs) are single-spanning
      transmembrane proteins that belong to the family of synaptically localized
      adhesion molecules that play various roles in the formation, maturation, and
      function of synapses. LRRTMs are highly localized in the post-synaptic density;
      however, the mechanisms and significance of LRRTM synaptic clustering remain
      unclear. Here, we focus on the intracellular domain of LRRTMs and investigate its
      role in cell surface expression and synaptic clustering. The deletion of 55-56
      residues in the cytoplasmic tail caused significantly reduced synaptic clustering
      of LRRTM1-4 in rat hippocampal neurons, whereas it simultaneously resulted in
      augmented LRRTM1-2 cell surface expression. A series of deletions and further
      single amino acid substitutions in the intracellular domain of LRRTM2
      demonstrated that a previously uncharacterized sequence at the region of -16 to 
      13 from the C-terminus was responsible for efficient synaptic clustering and
      proper cell surface trafficking of LRRTMs. Furthermore, the clustering-deficient
      LRRTM2 mutant lost the ability to promote the accumulation of post-synaptic
      density protein-95 (PSD-95). These results suggest that trafficking to the cell
      surface and synaptic clustering of LRRTMs are regulated by a specific mechanism
      through this novel sequence in the intracellular domain that underlies post
      synaptic molecular assembly and maturation. Leucine-rich repeat transmembrane
      proteins (LRRTMs) are synaptic cell adhesion molecules promoting synapse
      formation. LRRTMs are highly localized in the postsynaptic density. We report
      amino acid sequence YxxC in the intracellular domain of LRRTMs is responsible for
      the postsynaptic localization of LRRTMs. This novel amino acid sequence of LRRTMs
      facilitates synapse maturation. We propose this regulated synaptic clustering of
      LRRTMs by the intracellular domain presents a novel molecular mechanism of
      synapse maturation. 

PMID- 25951920
TI  - Internal jugular Venous Compression Syndrome: hemodynamic outcomes after cervical
      vertebral decompression manipulations.
AB  - OBJECTIVE: The AA studied hemodynamic effects in Venous Compression Syndrome of
      internal Jugular veins, after noninvasive treatment by RIMA (Ricci's
      manipulation) cervical manipulations. METHODS: Twenty-six subjects were enrolled
      with at least one jugular vein with complete (white) compression in frontal neck
      position, assessed by echo color Doppler. RESULTS: after first RIMA procedure we
      had a reduction of 81.25% (6/32) in the total number of internal jugular vein
      white compressions. CONCLUSIONS: Our results suggest that RIMA decompression
      method may be useful to restore the drainage of internal jugular veins when a
      white compression occurs. Considering the novelty of this work and the total
      absence of scientific similar works able to confirm this data, it is necessary to
      continue these studies in order to improve the management of this venous
      hemodynamic condition.

PMID- 25951921
TI  - Early skin reaction of polydioxanone suture material following septorhinoplasty.
AB  - BACKGROUND: Septorhinoplasty is a frequent surgical procedure used for both
      cosmetic and functional purposes. The technique varies from surgeon to surgeon
      and according to which suture material is used. While some surgeons prefer non
      absorbable sutures, others prefer sutures with delayed absorption. These
      materials sometimes protrude from the skin and they may cause skin reactions.
      While these reactions are common in the late period, a skin reaction in the early
      period because of polydioxanone suture is extremely rare and to the best of our
      knowledge, this is the first such reported case in the literature. CASE REPORT: A
      25-year-old male patient underwent endonasal septorhinoplasty procedure with endo
      tracheal general anesthesia. We hereby present the skin reaction because of
      frequently used polydioxanone suture on the 24th postoperative day and the
      management of this patient. We cut the suture at skin level and prescribed
      antibiotherapy, and we scheduled a follow-up for 10 days afterwards. The patient
      had no complaint and the control examination result was normal. CONCLUSIONS: When
      performing septorhinoplasty operations, very rare complications of the procedure
      shouldn't be ignored and an informed consent must be obtained after explaining
      possible complications before the operation. This approach is important for
      increasing the patient compliance and proper follow-up for the patient. This way,
      especially post-operative early complications as our case will be able to be
      solved with close follow-up and intervention, before causing permanent damage.
      The relationship between patient who underwent rhinoplasty and the physician also
      has an important role on these follow-up visits.

PMID- 25951922
TI  - Self-poisoning in the acute care medicine 2005-2012.
AB  - OBJECTIVE: To describe the trend of acute self-poisoning in the emergency and
      intensive care. METHODS: Electronic charts of adults who presented to the
      emergency department of the University Hospital Leipzig with self-poisoning
      following a suicide attempt (suicide group), intoxication (intoxication group),
      drug overdose for relief of pain or discomfort (drug overdose group) between 2005
      and 2012 were analyzed. RESULTS: 3533 adults (62.6% males) were identified, with
      the yearly admissions increasing from 305 in 2005 to 624 in 2012. The admission
      rate in relation to the total emergency department admissions also increased,
      from 1.2% in 2005 to 1.9% in 2012. 31.7% of the patients were younger than 25
      years. The reasons for self-poisoning were suicide attempt (18.1%), intoxication
      (76.8%) and drug overdose (2.9%). The reason could not be clearly classified in
      80 patients. Psychotropic drugs were used in 71.6% of suicide attempts, while
      alcohol was the sole cause of intoxication in 80.1% of cases in the intoxication
      group. Self-poisoning using at least two substances was observed in 52.0% of the
      suicide attempts, 10.3% of those with intoxication and 29.7% of those with drug
      overdose. While alcohol remains the most common cause of intoxication, there was
      a drastic increase in the consumption of cannabinoids, Crystal Meth and gamma
      hydroxybutyrate in the years 2011 and 2012. ICU admission was necessary in 16.6%
      of the cases. There were 22 deaths (0.6% of the study population), of whom 15
      were in the suicide group (2.3%), four (0.15%) in the intoxication group, and
      three in the not clearly classified group (3.8%). CONCLUSION: Acute self
      poisoning is an increasing medical issue. Psychotropic drugs remain the most
      common means of suicide attempt. Although alcohol intoxication is very frequent,
      intake of illicit drugs as the cause of emergency admission is increasing.

PMID- 25951923
TI  - Factors associated with nonresponse to proton pump inhibitors therapy in patients
      referred for esophageal pH-impedance monitoring.
AB  - Nonresponse to proton pump inhibitors (PPI) concerns up to 40% of patients
      treated for gastroesophageal reflux disease (GERD). Identifying predictive
      factors of nonresponse might help to optimize patients' treatment. The aim of
      this study was to determine clinical factors associated with nonresponse to PPI
      therapy in patients referred for pH-impedance monitoring. One hundred and sixty
      eight consecutive patients (105 females, mean age 52 years, range 17-83) were
      included between October 2011 and May 2013. Before the realization of high
      resolution manometry and 24-hour pH-impedance monitoring they completed a
      questionnaire including Rome III criteria for functional dyspepsia and irritable
      bowel syndrome (IBS). Comparisons between patients with and without PPI response
      were performed using chi-square or analysis of variance tests. One hundred and
      twenty-six patients (83%) were considered as PPI nonresponders and 26 (17%) as
      responders. No significant difference was observed for age and body mass index.
      No manometric and pH-impedance profiles were identified as associated with PPI
      response. The percentage of patients with functional dyspepsia and IBS was higher
      in PPI nonresponders patients than in responders (65.6% and 27.2%, respectively,
      vs. 38.5% and 7.7%, P = 0.01 and P = 0.03). This study confirms that functional
      digestive disorders are more frequent in patients with persistent GERD symptoms
      on PPI and they might be indicative of nonresponse to PPI therapy.

PMID- 25951924
TI  - Rates of admission for ambulatory care sensitive conditions in France in 2009
      2010: trends, geographic variation, costs, and an international comparison.
AB  - BACKGROUND: Admissions for ambulatory care sensitive conditions (ACSCs) are
      considered preventable and indicators of poor access to primary care. We wondered
      whether per-capita rates of admission for ACSCs in France demonstrated geographic
      variation, were changing, were related to other independent variables, or were
      comparable to those in other countries; further, we wanted to quantify the
      resources such admissions consume. METHODS: We calculated per-capita rates of
      admission for five categories (chronic, acute, vaccination preventable, alcohol
      related, and other) of ACSCs in 94 departments in mainland France in 2009 and
      2010, examined measures and causes of geographic variation in those rates,
      computed the costs of those admissions, and compared rates of admission for ACSCs
      in France to those in several other countries. RESULTS: The highest ACSC
      admission rates generally occurred in the young and the old, but rates varied
      across French regions. Over the 2-year period, rates of most categories of ACSCs
      increased; higher ACSC admission rates were associated with lower incomes and a
      higher supply of hospital beds. We found that the local supply of general
      practitioners was inversely associated with rates of chronic and total ACSC
      admission rates, but that this relationship disappeared if we accounted for
      patients' use of general practitioners in neighboring departments. ACSC
      admissions cost 4.755 billion euros in 2009 and 5.066 billion euros in 2010; they
      consumed 7.86 and 8.74 million bed days of care, respectively. France had higher
      rates of ACSC admissions than most other countries examined. CONCLUSIONS: Because
      admissions for ACSCs are generally considered a failure of outpatient care, cost
      French taxpayers substantial monetary and hospital resources, and appear to occur
      more frequently in France than in other countries, policymakers should prioritize
      targeted efforts to reduce them.

PMID- 25951926
TI  - An analytical expression for the D.I.P.-P.I.P. flexion interdependence in human
      fingers.
AB  - Empirical evidence shows that a strong correlation exists between the flexion
      angles of the distal and proximal interphalangeal (D.I.P., P.I.P.) joints of the
      human finger. Several authors measured this functional dependence, stating that
      the interdependence of D.I.P. and P.I.P. flexion is different for healthy
      individuals and patients displaying pathologies. The purpose of our study is to
      find an analytical expression for this correlation. METHODS: Following closely
      the anatomical in situ relations, we developed a two-dimensional kinematical
      model which expresses analytically the D.I.P.-P.I.P. angle correlation. Numerical
      values for the model were extracted from one healthy and one pathological case
      data set. RESULTS: The analytical form of the model allows for any P.I.P. angle
      not only to calculate the corre- sponding D.I.P. angle, but after first order
      differentiation with respect to the P.I.P. angle, it also shows the rate of
      change of the D.I.P. flexion. The model reproduces well the differences in the
      angular correlation of D.I.P. flexion of the two healthy-pathological data sets.
      Displaying the rate of change of D.I.P. flexion versus P.I.P. flexion provides an
      additional, clear-cut discriminatory tool between normal and pathological states.
      CONCLUSIONS: Information on differences between normal and pathological flexion
      of fingers is more pronounced and easier accessible from the derivatives of the
      D.I.P.-P.I.P. flexion behaviour than from direct angular correlation data. The
      analytical form of our model allows one to establish the rate of change of the
      D.I.P. angles, resulting in a better analysis of the situations at hand.

PMID- 25951925
TI  - Intra- and interobserver variability of whole-tumour apparent diffusion
      coefficient measurements in nephroblastoma: a pilot study.
AB  - BACKGROUND: The apparent diffusion coefficient (ADC) is potentially useful for
      assessing treatment response in nephroblastoma (Wilms tumour). However the
      precision of ADC measurements in these heterogeneous lesions is unknown.
      OBJECTIVE: To assess intra- and interobserver variability of whole-tumour ADC
      measurements in viable parts of nephroblastomas at diagnosis and after
      preoperative chemotherapy. MATERIALS AND METHODS: We included children with
      histopathologically proven nephroblastoma who had undergone MRI with diffusion
      weighted imaging before and after preoperative chemotherapy. Three independent
      observers performed whole-tumour ADC measurements of all lesions, excluding non
      enhancing areas. One observer evaluated all lesions on two occasions. We
      performed analyses using Bland-Altman plots and concordance correlation
      coefficient (CCC) calculations with 95% limits of agreement for median ADC,
      difference between pre- and post-chemotherapy median ADC (ADC shift) and
      percentage of pixels with ADC values <1.0 * 10(-3) mm(2)/s. RESULTS: In 22
      lesions (13 pretreatment and 9 post-treatment) in 10 children the interobserver
      variability in median ADC and ADC shift were within the interval of approximately
      +/-0.1 * 10(-3) mm(2)/s (limits of agreement for median ADC ranged -0.08-0.11 *
      10(-3) mm(2)/s and for ADC-shift -0.11-0.09 * 10(-3) mm(2)/s). The interobserver
      variability for percentage of low-ADC pixels was larger and also biased. The
      calculated CCC confirmed good intra- and interobserver agreement (rho-c ranging
      from 0.968 to 0.996). CONCLUSION: Measurements of whole-tumour ADC values
      excluding necrotic areas seem to be sufficiently precise for detection of
      chemotherapy-related change.

PMID- 25951927
TI  - Release of 5-Aminosalicylic Acid (5-ASA) from Mesalamine Formulations at Various
      pH Levels.
AB  - INTRODUCTION: Oral formulations of 5-aminosalicylic acid (5-ASA) for treatment of
      ulcerative colitis have been developed to minimize absorption prior to the drug
      reaching the colon. In this study, we investigate the release of 5-ASA from
      available oral mesalamine formulations in physiologically relevant pH conditions.
      METHODS: Release of 5-ASA from 6 mesalamine formulations (APRISO(r), Salix
      Pharmaceuticals, Inc., USA; ASACOL(r) MR, Procter & Gamble Pharmaceuticals UK
      Ltd.; ASACOL(r) HD, Procter & Gamble Pharmaceuticals, USA; MEZAVANT XL(r), Shire
      US Inc.; PENTASA(r), Ferring Pharmaceuticals, Ltd., UK; SALOFALK(r), Dr. Falk
      Pharma UK Ltd.) was evaluated using United States Pharmacopeia apparatus I and II
      at pH values of 1.0 (2 h), 6.0 (1 h), and 6.8 (8 h). Dissolution profiles were
      determined for each formulation, respectively. RESULTS: Of the tested
      formulations, only the PENTASA formulation demonstrated release of 5-ASA at pH
      1.0 (48%), with 56% cumulative release after exposure to pH 6.0 and 92% 5-ASA
      release after 6-8 h at pH 6.8. No other mesalamine formulation showed >1% drug
      release at pH 1.0. The APRISO formulation revealed 36% 5-ASA release at pH 6.0,
      with 100% release after 3 h at pH 6.8. The SALOFALK formulation revealed 11% 5
      ASA release at pH 6.0, with 100% release after 1 h at pH 6.8. No 5-ASA was
      released by the ASACOL MR, ASACOL HD, and MEZAVANT XL formulations at pH 6.0. At
      pH 6.8, the ASACOL MR and ASACOL HD formulations exhibited complete release of 5
      ASA after 4 and 2 h, respectively, and the MEZAVANT XL formulation demonstrated
      complete 5-ASA release over 6-7 h. CONCLUSION: 5-Aminosalicylic acid release
      profiles were variable among various commercially available formulations.
      FUNDING: Shire Development LLC.

PMID- 25951928
TI  - Effect of slaughter age on foal carcass traits and meat quality.
AB  - Meat has played a crucial role in human evolution and is an important component
      of a healthy and well-balanced diet due to its nutritional richness. Recent
      studies have shown that horsemeat may be considered as an alternative to other
      meat (such as beef or pork), and it may have a positive effect on human health
      from a nutritional point of view. This research was conducted to characterize the
      carcass measurement, meat quality (chemical composition, colour characteristics
      and textural traits) and nutritional value (fatty acid and amino acid
      composition) of foals slaughtered at 8 and 11 months of age (8 and 11 m groups).
      For this study, a total of 21 foals (10 and 11 animals from the 8 and 11-m
      groups, respectively) were used. The results obtained showed a positive influence
      on carcass characteristics with an increase in slaughter age, because 11 m
      animals had slightly higher values of live (275 v. 247 kg) and carcass weights
      (148 v. 133 kg), length of leg (72.86 v. 69.85 cm) and carcass (100.41 v. 96.30
      cm) and perimeter of leg (97.68 v. 89.22 cm) compared with animals from the 8-m
      group. Regarding meat quality, only Fe-haeme and cholesterol content in chemical
      composition and luminosity (L*) in colour parameters showed significant
      differences. Foals from the 8-m group had the highest content of cholesterol
      (0.47 v. 0.28 mg/100 g of meat) and luminosity values (39.66 v. 37.88) and the
      lowest content of ash (1.20% v. 1.40%). In fatty acids content, only five out of
      23 fatty acids showed differences between the two groups. However, an interesting
      change in the fatty acid profile occurred with an increase in the slaughter age.
      Foals from the 8-m group had the highest values of alpha-linolenic acid and n-3
      fatty acids and the lowest values of linoleic and n-6 fatty acids, which is an
      interesting fact from a health point of view. Finally, slaughter age had no
      statistical influence on textural properties or amino acid content. As a main
      conclusion, animals slaughtered at 8 months of age had higher nutritional quality
      meat (with higher content of n-3 fatty acids) than meat from foals slaughtered at
      11 months of age. The slaughter of animals at 8 months of age also reduced
      production costs because they ate a smaller amount of commercial fodder. 

PMID- 25951929
TI  - Diabetic retinopathy: recent advances towards understanding neurodegeneration and
      vision loss.
AB  - Diabetic retinopathy (DR) is one of the most common retinal diseases world-wide.
      It has a complex pathology that involves the vasculature of the inner retina and
      breakdown of the blood-retinal barrier. Extensive research has determined that DR
      is not only a vascular disease but also has a neurodegenerative component and
      that essentially all types of cells in the retina are affected, leading to
      chronic loss of visual function. A great deal of work using animal models of DR
      has established the loss of neurons and pathology of other cell types, including
      supporting glial cells. There has also been an increased emphasis on measuring
      retinal function in the models, as well as further validation and extension of
      the animal studies by clinical and translational research. This article will
      attempt to summarize the more recent developments in research towards
      understanding the complexities of retinal neurodegeneration and functional vision
      loss in DR. 

PMID- 25951930
TI  - Non-coding regions of the Ebola virus genome contain indispensable phylogenetic
      and evolutionary information.
AB  - We compared the numbers of nucleotide substitutions occurring in the non-coding
      regions and coding regions of Ebola virus genomes and found that non-coding
      regions contain indispensable phylogenetic and evolutionary information. The
      omission of genetic data from non-coding regions can lead to unreliable
      phylogenies and inaccurate estimates of evolutionary parameters. 

PMID- 25951931
TI  - Association between retinal neuronal degeneration and visual function impairment
      in type 2 diabetic patients without diabetic retinopathy.
AB  - The changes in retinal thickness and visual function in type 2 diabetic patients
      without clinical evidence of diabetic retinopathy were evaluated. A total of 141
      diabetic subjects without retinopathy and 158 healthy subjects were enrolled in
      this study. Superior macular ganglion cell complex thicknesses were significantly
      decreased in diabetic cases, and no significant peripapillary retinal nerve fiber
      layer thickness changes were observed. The contrast sensitivities at all space
      frequencies were significantly different between diabetic patients and controls.
      The mean P50 amplitude from pattern electroretinogram results was reduced
      significantly in the diabetic group. In the diabetic group, average superior
      ganglion cell complex thicknesses positively correlated with both contrast
      sensitivities at high spatial frequencies and P50 amplitudes. The results
      indicated that ganglion cell complex thickness and visual function changes could
      be observed in diabetic subjects before the onset of any significant diabetic
      retinopathy. Macular ganglion cell complex reduction occurred much earlier than
      peripapillary retinal nerve fiber layer thinning in diabetic patients without
      retinopathy. 

PMID- 25951932
TI  - Regulation of intestinal stem cell fate specification.
AB  - The remarkable ability of rapid self-renewal makes the intestinal epithelium an
      ideal model for the study of adult stem cells. The intestinal epithelium is
      organized into villus and crypt, and a group of intestinal stem cells located at
      the base of crypt are responsible for this constant self-renewal throughout the
      life. Identification of the intestinal stem cell marker Lgr5, isolation and in
      vitro culture of Lgr5+ intestinal stem cells and the use of transgenic mouse
      models have significantly facilitated the studies of intestinal stem cell
      homeostasis and differentiation, therefore greatly expanding our knowledge of the
      regulatory mechanisms underlying the intestinal stem cell fate determination. In
      this review, we summarize the current understanding of how signals of Wnt, BMP,
      Notch and EGF in the stem cell niche modulate the intestinal stem cell fate. 

PMID- 25951934
TI  - Whole-genome sequencing opens a new era for molecular breeding of grass carp
      (Ctenopharyngodon idellus).

PMID- 25951933
TI  - Apelin activates the expression of inflammatory cytokines in microglial BV2 cells
      via PI-3K/Akt and MEK/Erk pathways.
AB  - This paper aims to observe the changes of the inflammatory cytokines in
      microglial BV2 cells stimulated by apelin, and investigate the mechanism of
      inflammatory cytokines secretion after apelin stimulation. Immunofluorescence and
      quantitative real-time PCR were performed to observe expression of TNF-alpha, IL
      1beta, IL-10, MIP-1alpha, and MCP-1 in BV2 cells. Western blot was used to
      investigate the expression of phosphorylation PI-3K/Akt and phosphorylation Erk
      signaling pathways in BV2 cells after stimulation by apelin. Furthermore, PI
      3K/Akt inhibitor (LY294402) and Erk inhibitor (U0126) were used as antagonists to
      detect the secretion mechanisms of cytokines in BV2 cells stimulated by apelin.
      Exogenous recombinant apelin activated the expression of TNF-alpha, IL-1beta, MCP
      1 and MIP-1alpha in BV2 cells by the detection of fluorescence expression and
      mRNA. Apelin also unregulated the protein expression of p-PI-3K/Akt and p-Erk in
      BV2 cells induced by apelin. LY294002 and U0126 inhibited activation of p-PI
      3K/Akt and p-Erk expression by Western blot and attenuated the expression of
      inflammation factors in BV2 cells by fluorescence staining. This study
      demonstrates that apelin is a potential activator of inflammation factors through
      the PI3K/Akt and Erk signaling pathway and is potential therapeutically relevant
      to inflammatory responses of microglia cells. 

PMID- 25951935
TI  - Sequence types of Staphylococcus epidermidis associated with prosthetic joint
      infections are not present in the laminar airflow during prosthetic joint
      surgery.
AB  - Molecular characterization of Staphylococcus epidermidis isolates from prosthetic
      joint infections (PJIs) has demonstrated a predominance of healthcare-associated
      multi-drug resistant sequence types (ST2 and ST215). How, and when, patients
      acquire these nosocomial STs is not known. The aim was to investigate if sequence
      types of S. epidermidis associated with PJIs are found in the air during
      prosthetic joint surgery. Air sampling was undertaken during 17 hip/knee
      arthroplasties performed in operating theaters equipped with mobile laminar
      airflow units in a 500-bed hospital in central Sweden. Species identification was
      performed using MALDI-TOF MS and 16S rRNA gene analysis. Isolates identified as
      S. epidermidis were further characterized by MLST and antibiotic susceptibility
      testing. Seven hundred and thirty-five isolates were available for species
      identification. Micrococcus spp. (n = 303) and coagulase-negative staphylococci
      (n = 217) constituted the majority of the isolates. Thirty-two isolates of S.
      epidermidis were found. S. epidermidis isolates demonstrated a high level of
      allelic diversity with 18 different sequence types, but neither ST2 nor ST215 was
      found. Commensals with low pathogenic potential dominated among the airborne
      microorganisms in the operating field during prosthetic joint surgery. Nosocomial
      sequence types of S. epidermidis associated with PJIs were not found, and other
      routes of inoculation are therefore of interest in future studies.

PMID- 25951936
TI  - A coherent mathematical characterization of isotope trace extraction, isotopic
      envelope extraction, and LC-MS correspondence.
AB  - BACKGROUND: Liquid chromatography-mass spectrometry is a popular technique for
      high-throughput protein, lipid, and metabolite comparative analysis. Such
      statistical comparison of millions of data points requires the generation of an
      inter-run correspondence. Though many techniques for generating this
      correspondence exist, few if any, address certain well-known run-to-run LC-MS
      behaviors such as elution order swaps, unbounded retention time swaps, missing
      data, and significant differences in abundance. Moreover, not all extant
      correspondence methods leverage the rich discriminating information offered by
      isotope envelope extraction informed by isotope trace extraction. To date, no
      attempt has been made to create a formal generalization of extant algorithms for
      these problems. RESULTS: By enumerating extant objective functions for these
      problems, we elucidate discrepancies between known LC-MS data behavior and extant
      approaches. We propose novel objective functions that more closely model known LC
      MS behavior. CONCLUSIONS: Through instantiating the proposed objective functions
      in the form of novel algorithms, practitioners can more accurately capture the
      known behavior of isotope traces, isotopic envelopes, and replicate LC-MS data,
      ultimately providing for improved quantitative accuracy.

PMID- 25951937
TI  - Babesia spp. and other pathogens in ticks recovered from domestic dogs in
      Denmark.
AB  - BACKGROUND: Newly recognized endemic foci for human babesiosis include Europe,
      where Ixodes ricinus, a vector for several species of Babesia, is the most
      commonly identified tick. Vector-based surveillance provides an early warning
      system for the emergence of human babesiosis, which is likely to be under
      reported at emerging sites. In the present study, we set out to screen I. ricinus
      collected from Danish domestic dogs for Babesia, in order to identify whether
      humans in Denmark are exposed to the parasite. FINDINGS: A total of 661 ticks
      (Ixodes spp.) were collected from 345 Danish domestic dogs during April-September
      2011 and pooled, one sample per dog. DNA was extracted from each sample and
      examined by PCR and sequencing for Rickettsia spp., Borrelia burgdorferi sensu
      lato, Bartonella spp., Francisella tularensis, Candidatus Neoehrlichia
      mikurensis, and Babesia spp. In total, 34% of the samples were positive for tick
      borne microorganisms potentially pathogenic to humans: Rickettsia spp. were
      detected in 16% of the pools, with 79% being R. helvetica. Borrelia burgdorferi
      sensu lato was found in 15%, with the main species identified as Borrelia afzelii
      (39%). Likewise, 8% of the samples were positive for Babesia spp. (Babesia
      microti, 82%; Babesia venatorum ('EU1'), 18%). Lastly, 1% of the samples tested
      positive for Candidatus Neoehrlichia mikurensis, and 0.6% for Bartonella spp. No
      ticks were found to be infected with Francisella tularensis. CONCLUSIONS: Our
      data are in support of endemic occurrence of potentially zoonotic Babesia in
      Denmark and confirms I. ricinus as a vector of multiple pathogens of public
      health concern.

PMID- 25951938
TI  - Mepolizumab for eosinophilic severe asthma: recent studies.
AB  - INTRODUCTION: In September 2014 two large clinical studies of the anti-IL-5
      monoclonal antibody mepolizumab in severe asthma were published in the New
      England Journal of Medicine (MENSA and SIRIUS). AREAS COVERED: Eosinophilic
      inflammation has long been recognised as a feature of asthma. Identification of
      IL-5 as a key cytokine specific for eosinophil development and survival lead to
      development of monoclonal antibody therapy targeting this pathway. These two
      important new studies suggested that this treatment could reduce exacerbation
      rates by 50% in asthmatic patients with persistent peripheral blood eosinophilia
      and persistent symptoms despite high-dose-inhaled corticosteroids and additional
      controller therapy, and frequent exacerbations. In the second study, mepolizumab
      was shown to reduce oral steroid requirement by a median of 50% in similar
      patients who additionally required oral prednisone to control disease. EXPERT
      OPINION: This represents an important new treatment option in an area of unmet
      need, and together with a large dose ranging study (DREAM) published in 2012 form
      the basis for filing for registration in the USA and Europe.

PMID- 25951939
TI  - Application of simple and low-cost toxicity tests for ecotoxicological assessment
      of industrial wastewaters.
AB  - The objective of this study was to identify and to apply appropriate biotests
      having the advantages of being highly sensitive, easy to run, relatively
      inexpensive and able to substitute fish toxicity tests due to ethical reasons of
      animal welfare. To perform an ecotoxicological assessment of industrial
      wastewaters, different microbiotests were conducted to substitute the fish
      toxicity test with Lebistes reticulatus through Vibrio fischeri, Thamnocephalus
      platyurus, Daphnia magna, Lemna minor and Lepidium sativum representing different
      trophic levels in the aquatic and terrestrial ecosystems. Also, Algaltox F(TM)
      with Pseudokirchneriella subcapitata and Protox F(TM) with Tetrahymena
      thermophila tests were carried out. However, they could not be applied
      successfully for the wastewater samples. Wastewater samples from seven different
      industrial zones comprising different industries were subjected to
      characterization through measuring their physical-chemical parameters and their
      toxicity versus the above-mentioned organisms. T. platyurus, D. magna and L.
      reticulatus were the most sensitive test organisms investigated for the
      wastewaters. Considering toxic unit values, generally wastewater samples were
      toxic according to Thamnotox F(TM), Daphtox F(TM) and fish toxicity tests. As an
      important outcome, it was concluded that Daphtox F(TM) and Thamnotox F(TM) could
      be a good alternative for the fish toxicity test, which is so far the sole
      toxicity test accepted by the Turkish Water Pollution Control Regulation. 

PMID- 25951940
TI  - Presentation of youth with type 2 diabetes in the Pediatric Diabetes Consortium.
AB  - OBJECTIVE: Type 2 diabetes (T2D) in youth is recognized as a pediatric disease,
      but few reports describe the characteristics during diagnosis. We describe the
      clinical presentation of 503 youth with T2D. METHODS: The Pediatric Diabetes
      Consortium (PDC) T2D Clinic Registry enrolled T2D participants from eight
      pediatric diabetes centers in the USA. Clinical and laboratory characteristics at
      the time of diagnosis were analyzed. RESULTS: In total 67% presented with
      symptoms of diabetes and confirming laboratory data, but 33% were identified by
      testing at risk children, 11% presented with diabetic ketoacidosis (DKA), and 2%
      with hyperglycemic hyperosmolar state (HHS). The mean age was 13.1 +/- 2.3 yr
      (range, 4.6-19.8 yr) with 38 (8%) less than 10 yr of age at diagnosis. The
      majority was female (65%), Hispanic (54%) and had a family history of T2D (92%).
      The median body mass index (BMI) z-score was 2.3 (interquartile range 2.0-2.6).
      Fewer than half (46%) lived with both parents, only 30% had parents with
      education beyond high school, and 43% lived in a household with an income of <$25
      000 per year. In the initial month after diagnosis, almost all (92%) were treated
      with insulin (30%), metformin (31%), or a combination of insulin and metformin
      (32%); 7% were treated with lifestyle modification alone. CONCLUSIONS: The
      demographics of T2D in youth indicate significant social vulnerability which may
      affect outcomes. Metformin and insulin were the initial treatment in most youth.
      Importantly, T2D may occur at younger ages than previously thought and should be
      considered in all high-risk children presenting with diabetes.

PMID- 25951942
TI  - MOF-derived, N-doped, hierarchically porous carbon sponges as immobilizers to
      confine selenium as cathodes for Li-Se batteries with superior storage capacity
      and perfect cycling stability.
AB  - Nitrogen-doped carbon sponges (NCS) composed of hierarchical microporous carbon
      layers are derived from metal organic frameworks (MOFs) via carbonization at high
      temperatures under Ar and NH3 flow. Se is impregnated into 0.4-0.55 nm micropores
      by melting-diffusion and infiltration methods. The confinement of Se within small
      sized micropores of NCS efficiently prevents Se loss, and mesopores between
      carbon layers absorb a sufficient amount of electrolyte, as well as serve as
      cushion spaces for large volume changes during delithiation-lithiation processes.
      Nitrogen doping improves the electrical conductivity of carbon matrix and
      facilitates rapid charge transfer, making the carbon sponge a highway for charges
      involved in redox reactions. When serving as cathode materials for Li-Se
      batteries, the NCS/Se-50 composite with 50 wt% Se exhibits excellent cycling
      stability, superior rate capability and high coulombic efficiency. The cathode
      can exhibit 443.2 mA h g(-1) at the 200(th) cycle with a coulombic efficiency of
      up to 99.9% at 0.5C (C = 675 mA h g(-1)), which leads to 0.031% capacity loss per
      cycle from 5(th) to 200(th) cycles. Even at a high rate of 5C, it can still
      retain 286.6 mA h g(-1). The unique, large surface rod-like MOF-derived, N-doped
      carbon sponges with hierarchical porosity could be potential candidates in the
      related energy-storage systems. 

PMID- 25951941
TI  - The role of epigenetics in personalized medicine: challenges and opportunities.
AB  - Epigenetic alterations are considered to be very influential in both the normal
      and disease states of an organism. These alterations include methylation,
      acetylation, phosphorylation, and ubiquitylation of DNA and histone proteins
      (nucleosomes) as well as chromatin remodeling. Many diseases, such as cancers and
      neurodegenerative disorders, are often associated with epigenetic alterations.
      DNA methylation is one important modification that leads to disease. Standard
      therapies are given to patients; however, few patients respond to these drugs,
      because of various molecular alterations in their cells, which may be partially
      due to genetic heterogeneity and epigenetic alterations. To realize the promise
      of personalized medicine, both genetic and epigenetic diagnostic testing will be
      required. This review will discuss the advances that have been made as well as
      the challenges for the future. 

PMID- 25951944
TI  - Verb production tasks in the measurement of communicative abilities in aphasia.
AB  - BACKGROUND: The neurofunctional correlates of verbs and nouns have been the focus
      of many theoretically oriented studies. In clinical practice, however, more
      attention is typically paid to nouns, and the relative usefulness of tasks
      probing nouns and verbs is unclear. The routine administration of tasks that use
      verbs could be a relevant addition to current batteries. Evaluating performance
      on both noun and verb tasks may provide a more reliable account of everyday
      language abilities than an evaluation restricted to nouns. AIMS: To assess the
      benefits of administering verb tasks in addition to noun tasks, and their
      relation to three functional measures of language. METHOD AND PROCEDURE: Twenty
      one subjects with poststroke language disorders completed four picture-naming
      tasks and a role-playing test (Communicative Abilities in Daily Living, Second
      Edition, CADL-2), commonly used as measure of everyday language abilities. Two
      questionnaires (Communicative Effectiveness Index, CETI, and Communicative
      Activity Log, CAL) were completed by caregivers. Picture-naming tasks were
      matched for psycholinguistic variables to avoid lexicosemantic and
      morphosyntactic confounds. RESULTS: No significant differences emerged across
      picture-naming tasks. Scores on the role-playing test and the two questionnaires
      differed; scores between the two questionnaires did not. The four naming tasks
      correlated significantly with CADL-2, CETI, and CAL. The strength of the
      correlation with CADL-2 was significantly greater for Naming Finite Verbs than
      for Object Naming. Thirteen participants showed no differences in performance
      between tasks, 6 fared significantly worse on verb tasks than on Object Naming, 1
      fared better at Naming Finite Verbs though his performance was poor overall, and
      1 was significantly more impaired on verbs. CONCLUSIONS: Performance on tasks
      that use verbs, and especially Naming Finite Verbs, may provide a more accurate
      estimate of language abilities in daily living than Object Naming alone.
      Administering both verb and noun tasks may be recommended in clinical practice.

PMID- 25951943
TI  - The orphan nuclear receptor small heterodimer partner is required for
      thiazolidinedione effects in leptin-deficient mice.
AB  - BACKGROUND: Small heterodimer partner (SHP, NR0B2) is involved in diverse
      metabolic pathways, including hepatic bile acid, lipid and glucose homeostasis,
      and has been implicated in effects on the peroxisome proliferator-activated
      receptor gamma (PPARgamma), a master regulator of adipogenesis and the receptor
      for antidiabetic drugs thiazolidinediones (TZDs). In this study, we aim to
      investigate the role of SHP in TZD response by comparing TZD-treated leptin
      deficient (ob/ob) and leptin-, SHP-deficient (ob/ob;Shp(-/-)) double mutant mice.
      RESULTS: Both ob/ob and double mutant ob/ob;Shp(-/-) mice developed
      hyperglycemia, insulin resistance, and hyperlipidemia, but hepatic fat
      accumulation was decreased in the double mutant ob/ob;Shp(-/-) mice. PPARgamma2
      mRNA levels were markedly lower in ob/ob;Shp(-/-) liver and decreased to a lesser
      extent in adipose tissue. The TZD troglitazone did not reduce glucose or
      circulating triglyceride levels in ob/ob;Shp(-/-) mice. Expression of the
      adipocytokines, such as adiponectin and resistin, was not stimulated by
      troglitazone treatment. Expression of hepatic lipogenic genes was also reduced in
      ob/ob;Shp(-/-) mice. Moreover, overexpression of SHP by adenovirus infection
      increased PPARgamma2 mRNA levels in mouse primary hepatocytes. CONCLUSIONS: Our
      results suggest that SHP is required for both antidiabetic and hypolipidemic
      effects of TZDs in ob/ob mice through regulation of PPARgamma expression.

PMID- 25951946
TI  - Multi-platinum anti-cancer agents. Substitution-inert compounds for tumor
      selectivity and new targets.
AB  - This tutorial review summarizes chemical, biophysical and cellular biological
      properties of formally substitution-inert "non-covalent" polynuclear platinum
      complexes (PPCs). We demonstrate how modulation of the pharmacological factors
      affecting platinum compound cytotoxicity such as cellular accumulation,
      reactivity toward extracellular and intracellular sulfur-ligand nucleophiles and
      consequences of DNA binding is achieved to afford a profile of biological
      activity distinct from that of covalently-binding agents. The DNA binding of
      substitution-inert complexes is achieved by molecular recognition through minor
      groove spanning and backbone tracking of the phosphate clamp. In this situation,
      the square-planar tetra-am(m)ine Pt(ii) coordination units hydrogen bond to
      phosphate oxygen OP atoms to form bidentate N-O-N motifs. The modular nature of
      the polynuclear compounds results in high-affinity binding to DNA and very
      efficient nuclear condensation. These combined effects distinguish the phosphate
      clamp as a third mode of ligand-DNA binding, discrete from intercalation and
      minor-groove binding. The cellular consequences mirror those of the biophysical
      studies and a significant portion of nuclear DNA is compacted, a unique effect
      different from mitosis, senescence or apoptosis. Substitution-inert PPCs display
      cytotoxicity similar to cisplatin in a wide range of cell lines, and sensitivity
      is indifferent to p53 status. Cellular accumulation is mediated through binding
      to heparan sulfate proteoglycans (HSPG) allowing for possibilities of tumor
      selectivity as well as disruption of HSPG function, opening new targets for
      platinum antitumor agents. The combined properties show that covalently-binding
      chemotypes are not the unique arbiters of cytotoxicity and antitumor activity and
      meaningful antitumor profiles can be achieved even in the absence of Pt-DNA bond
      formation. These dual properties make the substitution-inert compounds a unique
      class of inherently dual-action anti-cancer agents. 

PMID- 25951947
TI  - Performance of a blockwise approach in variable selection using linkage
      disequilibrium information.
AB  - BACKGROUND: Genome-wide association studies (GWAS) aim at finding genetic markers
      that are significantly associated with a phenotype of interest. Single nucleotide
      polymorphism (SNP) data from the entire genome are collected for many thousands
      of SNP markers, leading to high-dimensional regression problems where the number
      of predictors greatly exceeds the number of observations. Moreover, these
      predictors are statistically dependent, in particular due to linkage
      disequilibrium (LD). We propose a three-step approach that explicitly takes
      advantage of the grouping structure induced by LD in order to identify common
      variants which may have been missed by single marker analyses (SMA). In the first
      step, we perform a hierarchical clustering of SNPs with an adjacency constraint
      using LD as a similarity measure. In the second step, we apply a model selection
      approach to the obtained hierarchy in order to define LD blocks. Finally, we
      perform Group Lasso regression on the inferred LD blocks. We investigate the
      efficiency of this approach compared to state-of-the art regression methods:
      haplotype association tests, SMA, and Lasso and Elastic-Net regressions. RESULTS:
      Our results on simulated data show that the proposed method performs better than
      state-of-the-art approaches as soon as the number of causal SNPs within an LD
      block exceeds 2. Our results on semi-simulated data and a previously published
      HIV data set illustrate the relevance of the proposed method and its robustness
      to a real LD structure. The method is implemented in the R package BALD
      (Blockwise Approach using Linkage Disequilibrium), available from http://www.math
      evry.cnrs.fr/publications/logiciels . CONCLUSIONS: Our results show that the
      proposed method is efficient not only at the level of LD blocks by inferring well
      the underlying block structure but also at the level of individual SNPs. Thus,
      this study demonstrates the importance of tailored integration of biological
      knowledge in high-dimensional genomic studies such as GWAS.

PMID- 25951945
TI  - Sub-lingual administration of a polyvalent mechanical bacterial lysate (PMBL) in
      patients with moderate, severe, or very severe chronic obstructive pulmonary
      disease (COPD) according to the GOLD spirometric classification: A multicentre,
      double-blind, randomised, controlled, phase IV study (AIACE study: Advanced
      Immunological Approach in COPD Exacerbation).
AB  - Polyvalent mechanical bacterial lysates (PMBLs) have been shown to reduce the
      number of infectious episodes in patients with recurrent infections of the
      respiratory tract. Some previous investigations have also shown the effectiveness
      of PMBLs in reducing exacerbations of chronic obstructive pulmonary disease
      (COPD). The AIACE study, which was developed according to criteria of evidence
      based medicine, evaluated whether the administration of PMBLs to COPD patients,
      in addition to the recommended treatment, was able to reduce the number of
      exacerbations by 25%. Two hundred eighty-eight patients with moderate to very
      severe COPD were recruited and randomly assigned to either placebo or PMBLs. The
      placebo or PMBLs were administered according to the standard scheme. The primary
      outcome of the study was not achieved. However, the number of days with fever (21
      days per year versus 40.15; p < 0.001), the days of hospitalisation (65 days vs
      162 days; p < 0.001), the interval between the first and second exacerbations
      (123.89 days vs 70.36; p = 0.03) and the number of days in poor health (109
      days/year vs 171 days/year; p < 0.001) were significantly better in the PMBL
      group than in the placebo group. In conclusion, the results of this trials showed
      that Ismigen, in addition to guideline-suggested treatment, could not
      significantly reduce the number of exacerbations in the considered population;
      nevertheless, the secondary outcome results demonstrated potential benefits of
      this compound for relevant clinical outcomes. 

PMID- 25951948
TI  - Estimation of Purkait's triangle method and alternative models for sex assessment
      from the proximal femur in the Spanish population.
AB  - The current study was undertaken to test the validity and reproducibility of the
      Purkait triangle method and some alternative proposals for sex prediction from
      the proximal femur in the adult population of Spain. To that end, sexual
      dimorphism of the maximum femoral head diameter and the minimum femoral neck
      diameter were also evaluated. The study was conducted on 186 femora (109 males
      and 77 females) taken from the San Jose collection of identified individuals
      (Southern Spain). Discriminant function analyses (DFA) employing the jackknife
      procedure for cross-validations were considered. Overall, more than 94% of
      individuals of both sexes were correctly classified. The most dimorphic single
      variable from the triangle method was the intertrochanteric apex distance (BC)
      that reached 85.5% accuracy, falling below those obtained for the femoral head
      and femoral neck diameter, respectively, (89.8 and 91.9%). Combining BC with the
      neck diameter, the predictive ability increased to 92.5%; when femoral head
      diameter was added to the latter two, the classification success rate improved
      further up to 94.6% (94.1% after cross-validation). We conclude that the
      classification success rates of the Purkait's method remained considerably below
      any of those obtained with the models proposed in the present study which proved
      to be a much better and more reliable choice both as single predictors and in
      combination with other variables.

PMID- 25951949
TI  - Living with chronic illness in adults: a concept analysis.
AB  - AIMS AND OBJECTIVES: To report an analysis of the concept of Living with chronic
      illness in adults, using Rodger's evolutionary analytical methodology.
      BACKGROUND: In the literature, several qualitative studies exist that address the
      question of Living with chronic illness from the adult patient's perspective.
      However, the lack of clarity and consensus among the existing studies renders
      this concept ambiguous when it is analysed in depth. DESIGN: A narrative review.
      METHODS: A systematic search has been carried out on electronic databases such as
      Medline (PubMed), Cinahl (Ebsco), Cochrane Library, PsycINFO (Ovid), Embase,
      Cuiden, Dialnet and Scielo. This was limited to articles published in either
      Spanish or English, from 2003-2013. RESULTS: Living with chronic illness is a
      complex, dynamic, cyclic and multidimensional process, and involves the
      development of five different attributes: Acceptance, Coping, Self-management,
      Integration and Adjustment. Depending on how these attributes operate, there are
      four different ways of living which can result from the process of Living with
      chronic illness: (1) Disavowal, (2) False Normality, (3) The New Normal and (4)
      Disruption. CONCLUSIONS: This paper contributes to the understanding of the
      concept 'Living with chronic illness'. Findings in this analysis have to be
      evaluated with caution and further research is needed on this topic to confirm
      them. Also, more studies in evaluating how patients live a long-term condition
      are recommended to foster patient-centred care. RELEVANCE TO CLINICAL PRACTICE:
      Findings generated from this concept analysis can raise awareness of Living with
      chronic illness so that this process could be assessed in a correct and uniform
      way in the clinical community and improved when needed.

PMID- 25951950
TI  - [Travel memories].

PMID- 25951951
TI  - Determination of body fat mass: bioelectrical impedance analysis.

PMID- 25951952
TI  - Reply to 'letter to the editor'.

PMID- 25951953
TI  - An organizational readiness intervention and randomized controlled trial to test
      strategies for implementing substance use disorder treatment into primary care:
      SUMMIT study protocol.
AB  - BACKGROUND: Millions of people who need treatment for substance use disorders
      (SUD) do not receive it. Evidence-based practices for treating SUD exist, and
      some are appropriate for delivery outside of specialty care settings. Primary
      care is an opportune setting in which to deliver SUD treatment because many
      individuals see their primary care providers at least once a year. Further, the
      Patient Protection and Affordable Care Act (PPACA) increases coverage for SUD
      treatment and is increasing the number of individuals seeking primary care
      services. In this article, we present the protocol for a study testing the
      effects of an organizational readiness and service delivery intervention on
      increasing the uptake of SUD treatment in primary care and on patient outcomes.
      METHODS/DESIGN: In a randomized controlled trial, we test the combined effects of
      an organizational readiness intervention consisting of implementation tools and
      activities and an integrated collaborative care service delivery intervention
      based on the Chronic Care Model on service system (patient-centered care,
      utilization of substance use disorder treatment, utilization of health care
      services and adoption and sustainability of evidence-based practices) and patient
      (substance use, consequences of use, health and mental health, and satisfaction
      with care) outcomes. We also use a repeated measures design to test
      organizational changes throughout the study, such as acceptability,
      appropriateness and feasibility of the practices to providers, and provider
      intention to adopt the practices. We use provider focus groups, provider and
      patient surveys, and administrative data to measure outcomes. DISCUSSION: The
      present study responds to critical gaps in health care services for people with
      substance use disorders, including the need for greater access to SUD treatment
      and greater uptake of evidence-based practices in primary care. We designed a
      multi-level study that combines implementation tools to increase organizational
      readiness to adopt and sustain evidence-based practices (EBPs) and tests the
      effectiveness of a service delivery intervention on service system and patient
      outcomes related to SUD services. TRIAL REGISTRATION: Current controlled trials:
      NCT01810159.

PMID- 25951954
TI  - Does the new EU Regulation on clinical trials adequately protect vulnerable
      research participants?
AB  - Vulnerable research participants deserve special protection because of their
      increased risks of being wronged. Yet, paradoxically, the conduct of trials
      involving vulnerable groups is sometimes inescapable to develop safe and
      efficient therapies suitable to these groups. The key question is therefore how
      to protect vulnerable research participants from harm and exploitation without
      excluding the populations they belong to from the benefits of research. The
      European Union faced this challenge in April 2014 when adopting the new
      Regulation on clinical trials, which will replace the currently applicable 2001
      Clinical Trials Directive in 2016. In order to assess the protection of
      vulnerable persons in the new Regulation, this paper makes four suggestions:
      first, the need to adopt a risk-based approach to vulnerability in biomedical
      research; second, to better distinguish between decisional vulnerabilities and
      health-related vulnerabilities; third, to emphasise the need to preserve the
      freedom of consent of subjects with decisional vulnerability, who are more
      susceptible to undue influence; and finally to assert the need of actively
      promoting specific clinical trials involving people with physical or
      psychological vulnerabilities. In conclusion, this paper claims that the
      protection of vulnerable subjects still needs to be improved in the new EU
      Regulation. 

PMID- 25951956
TI  - Cone beam computed tomography scanning and diagnosis for dental implants.
AB  - Cone beam computed tomography (CBCT) has become an important new technology for
      oral and maxillofacial surgery practitioners. CBCT provides improved office-based
      diagnostic capability and applications for surgical procedures, such as CT
      guidance through the use of computer-generated drill guides. A thorough knowledge
      of the basic science of CBCT as well as the ability to interpret the images
      correctly and thoroughly is essential to current practice.

PMID- 25951957
TI  - Simple bone augmentation for alveolar ridge defects.
AB  - Dental implant procedures, both surgical placement and preimplant bone
      augmentation, have become an integral aspect of the oral and maxillofacial
      surgeon's practice. The number of dental implants placed each year continues to
      increase as a result of increasing patient exposure and awareness of dental
      implants, the increased functional and esthetic dental demands of general
      practitioners and patients, the overall increase in age of the US patient
      population, and expanded insurance coverage of dental implant-related procedures.
      This article outlines relevant surgical procedures aimed toward reconstructing
      alveolar ridge defects to restore intra-arch alveolar discrepancies before
      restoration-driven dental implant placement. 

PMID- 25951958
TI  - Complex bone augmentation in alveolar ridge defects.
AB  - The current gold standard for bone grafting is autogenous bone, due to its
      biocompatibility, lack of antigenicity, osteoconductive, and osteoinducive
      properties. Radiography using cone-beam computed tomography for complex defects
      is useful in determining the amount of bone available and what bone augmentation
      technique will be needed. Many options for treatment of alveolar ridge defects
      are available, including varying surgical techniques as well as bone graft
      options.

PMID- 25951959
TI  - Prosthodontic Considerations in Post-cancer Reconstructions.
AB  - The restoration of function after oncologic surgery of the oral cavity
      constitutes one of the major challenges facing head and neck oncology. Within the
      general objective of securing esthetic as well as functional reconstructions,
      dental rehabilitation is crucial for achieving a good outcome. Adequate dental
      rehabilitation allows the patient to chew food and considerably improves speech
      and swallowing. These reconstructions will be driven biologically or
      prosthetically following surgical design and outcome. 

PMID- 25951960
TI  - Treatment of the edentulous patient.
AB  - For decades the edentulous population has been unrecognized in its need to be
      treated in an effective manner. The debilitating condition affects quality of
      life. Implants have provided a strategy for developing a standard of care. The
      McGill consensus statement provided evidence that 2 implants supporting a
      mandibular overdenture should be the first choice in the treatment of edentulism.
      Success in implementing this standard of care into an institution's curriculum
      depends on a close collaboration between the surgeon and the restoring dentist
      and an understanding of biomechanics and bone biology. 

PMID- 25951961
TI  - Esthetic implant site development.
AB  - Bony support is critical for creating and maintaining esthetic and natural
      appearing peri-implant soft tissue profiles. A variety of techniques have been
      shown to be effective for augmenting bone and soft tissue. Ideal implant position
      and angulation is critical for a natural-appearing outcome. Achieving an ideal
      esthetic result in the compromised site is often elusive and in many cases,
      impossible. This article reviews techniques available for esthetic implant site
      development. A review of the recent literature discovers the most effective
      techniques for achieving esthetic results. 

PMID- 25951962
TI  - Digital technologies for dental implant treatment planning and guided surgery.
AB  - Oral and maxillofacial surgeons now have extraordinary imaging, software
      planning, and guide fabrication technologies at their disposal to aid in their
      case selection, clinical decision making, and surgical procedures for dental
      implant placement. Cone beam CT has opened a new era of office-based diagnostic
      capability and responsibility. Improved clinical experiences and evidence-based
      superior outcomes can be provided with confidence to patients when CT-guided
      dental implant surgery is used. 

PMID- 25951955
TI  - Vasopressin and oxytocin receptor systems in the brain: Sex differences and sex
      specific regulation of social behavior.
AB  - The neuropeptides vasopressin (VP) and oxytocin (OT) and their receptors in the
      brain are involved in the regulation of various social behaviors and have emerged
      as drug targets for the treatment of social dysfunction in several sex-biased
      neuropsychiatric disorders. Sex differences in the VP and OT systems may
      therefore be implicated in sex-specific regulation of healthy as well as impaired
      social behaviors. We begin this review by highlighting the sex differences, or
      lack of sex differences, in VP and OT synthesis in the brain. We then discuss the
      evidence showing the presence or absence of sex differences in VP and OT
      receptors in rodents and humans, as well as showing new data of sexually
      dimorphic V1a receptor binding in the rat brain. Importantly, we find that there
      is lack of comprehensive analysis of sex differences in these systems in common
      laboratory species, and we find that, when sex differences are present, they are
      highly brain region- and species-specific. Interestingly, VP system parameters
      (VP and V1aR) are typically higher in males, while sex differences in the OT
      system are not always in the same direction, often showing higher OT expression
      in females, but higher OT receptor expression in males. Furthermore, VP and OT
      receptor systems show distinct and largely non-overlapping expression in the
      rodent brain, which may cause these receptors to have either complementary or
      opposing functional roles in the sex-specific regulation of social behavior.
      Though still in need of further research, we close by discussing how
      manipulations of the VP and OT systems have given important insights into the
      involvement of these neuropeptide systems in the sex-specific regulation of
      social behavior in rodents and humans. 

PMID- 25951963
TI  - Dental implants and evolving discipline.

PMID- 25951964
TI  - Measuring the corticosteroid responsiveness endophenotype in asthmatic patients.
AB  - BACKGROUND: Inhaled corticosteroids are the most commonly used controller
      therapies for asthma, producing treatment responses in 6 clinical phenotypes:
      lung function, bronchodilator response, airway responsiveness, symptoms, need for
      oral steroids and frequency of emergency department visits and hospitalizations.
      We hypothesize that treatment response in all of these phenotypes is modulated by
      a single quantitative corticosteroid responsiveness endophenotype. OBJECTIVE: We
      sought to develop a composite phenotype that combines multiple clinical
      phenotypes to measure corticosteroid responsiveness with high accuracy, stability
      across populations, and robustness to missing data. METHODS: We used principal
      component analysis to determine a composite corticosteroid responsiveness
      phenotype that we tested in 4 replication populations. We evaluated the relative
      accuracy with which the composite and clinical phenotypes measure the
      endophenotype using treatment effect area under the receiver operating
      characteristic curve (AUC). RESULTS: In the study population the composite
      phenotype measured the endophenotype with an AUC of 0.74, significantly exceeding
      the AUCs of the 6 individual clinical phenotypes, which ranged from 0.56 (P <
      .001) to 0.67 (P = .015). In 4 replication populations with a total of 22
      clinical phenotypes available, the composite phenotype AUC ranged from 0.69 to
      0.73, significantly exceeded the AUCs of 14 phenotypes, and was not significantly
      exceeded by any single phenotype. CONCLUSION: The composite phenotype measured
      the endophenotype with higher accuracy, higher stability across populations, and
      higher robustness to missing data than any clinical phenotype. This should
      provide the capability to model corticosteroid pharmacologic response and
      resistance with increased accuracy and reproducibility.

PMID- 25951965
TI  - Safety surrogate histograms (SSH): A novel real-time safety assessment of dilemma
      zone related conflicts at signalized intersections.
AB  - Drivers' indecisiveness in dilemma zones (DZ) could result in crash-prone
      situations at signalized intersections. DZ is to the area ahead of an
      intersection in which drivers encounter a dilemma regarding whether to stop or
      proceed through the intersection when the signal turns yellow. An improper
      decision to stop by the leading driver, combined with the following driver
      deciding to go, can result in a rear-end collision, unless the following driver
      recognizes a collision is imminent and adjusts his or her behavior at or shortly
      after the onset of yellow. Considering the significance of DZ-related crashes, a
      comprehensive safety measure is needed to characterize the level of safety at
      signalized intersections. In this study, a novel safety surrogate measure was
      developed utilizing real-time radar field data. This new measure, called safety
      surrogate histogram (SSH), captures the degree and frequency of DZ-related
      conflicts at each intersection approach. SSH includes detailed information
      regarding the possibility of crashes, because it is calculated based on the
      vehicles conflicts. An example illustrating the application of the new
      methodology at two study sites in Virginia is presented and discussed, and a
      comparison is provided between SSH and other DZ-related safety surrogate measures
      mentioned in the literature. The results of the study reveal the efficacy of the
      SSH as complementary to existing surrogate measures. 

PMID- 25951966
TI  - Structural snapshots of the SCR reaction mechanism on Cu-SSZ-13.
AB  - The structure of copper sites in Cu-SSZ-13 during NH3-SCR was unravelled by a
      combination of novel operando X-ray spectroscopic techniques. Strong adsorption
      of NH3 on Cu, its reaction with weakly adsorbed NO from the gas phase, and slow
      re-oxidation of Cu(I) were proven. Thereby the SCR reaction mechanism is
      significantly different to that observed for Fe-ZSM-5.

PMID- 25951967
TI  - Genome sequence of a novel endornavirus from the phytopathogenic fungus
      Alternaria brassicicola.
AB  - In an effort to discover new mycoviruses from phytopathogenic fungi, a dsRNA
      molecule of 10,290 nt, resembling those associated with the viruses belonging to
      the family Endornaviridae, was isolated from Alternaria brassicicola, one of the
      causal agents of rapeseed black spot disease. Genome analysis revealed the
      presence of a single open reading frame coding for a polyprotein of 3400 aa
      containing conserved viral methyltransferase (MTR), viral RNA helicase 1 (Hel-1),
      and RNA-dependent RNA polymerase (RdRp) domains. In addition, a cysteine-rich
      region (CRR) with conserved CXCC motifs, shared among several endornaviruses, was
      also identified between the MTR and Hel-1 domains. Phylogenetic analysis based on
      the RdRp sequence strongly suggested that the virus infecting A. brassicicola
      should be considered a representative of a novel endornavirus species, and this
      virus was designated as Alternaria brassicicola endornavirus 1 (AbEV1). 

PMID- 25951968
TI  - First complete genomic characterization and phylogeny of a new recombinant of
      tomato yellow leaf curl virus (genus Begomovirus, family Geminiviridae) from
      Kuwait.
AB  - While whitefly-transmitted begomoviruses are economically important constraints
      to tomato production in Kuwait, little is known about genomic features of these
      viruses from Kuwait. A begomovirus isolated from severely diseased tomatoes,
      collected over a two-year period in the main tomato-growing areas of Kuwait, was
      characterized at the molecular level. The complete genomic sequence of the
      begomovirus was determined, and phlylogeographic studies were conducted to better
      understand genetic diversity of the virus in the region. Based on genome
      properties and phylogenetic analysis, the begomovirus was found to be a strain of
      tomato yellow leaf curl virus (TYLCV). The virus genome was monopartite, as
      neither DNA B nor satellite DNA molecules were detected. Two isolates
      characterized in this study shared 97% and 95% nucleotide sequence identity with
      a previously characterized Kuwaiti isolate, TYLCV-KISR. Among TYLCV isolates with
      known genome sequences, the Kuwaiti isolates shared highest sequence identity
      (95%) with TYLCV-Almeria (Spain). Genetic diversity and phylogenetic analysis
      showed that the three Kuwaiti isolates formed a distinct clade that was separate
      from those of known TYLCV sequences. One Kuwaiti isolate (KW 1-3) could be a
      novel variant of TYLCV. Two recombination events were detected in the genome
      sequence of KW 1-3, which appeared to be a recombinant derived from TYLCV parents
      from Oman and Kuwait.

PMID- 25951969
TI  - Diversity of VP7, VP4, VP6, NSP2, NSP4, and NSP5 genes of porcine rotavirus C:
      phylogenetic analysis and description of potential new VP7, VP4, VP6, and NSP4
      genotypes.
AB  - Rotavirus C (RVC) is a cause of gastroenteritis in swine and has a worldwide
      distribution. A total of 448 intestinal or faecal samples from pigs of all ages
      were tested for viruses causing gastroenteritis. RVC was detected in 118 samples
      (26.3%). To gain information on virus diversity, the complete coding nucleotide
      sequences of the VP7, VP4, VP6, NSP2, NSP4, and NSP5 genes of seven RVC strains
      were determined. Phylogenetic analysis of VP7 nucleotide sequence divided studied
      Czech strains into six G genotypes (G1, G3, G5-G7, and a newly described G10
      genotype) based on an 85% identity cutoff value at the nucleotide level. Analysis
      of the VP4 gene revealed low nucleotide sequence identities between two Czech
      strains and other porcine (72.2-75.3%), bovine (74.1-74.6%), and human (69.1
      69.3%) RVC strains. Thus, we propose that those two Czech porcine strains
      comprise a new RVC VP4 genotype, P8. Analysis of the VP6 gene showed 79.9-86.8%
      similarity at the nucleotide level between the Czech strains and other porcine
      RVC strains. According to the 87% identity cutoff value, we propose the existence
      of three new RVC VP6 genotypes, I8-I10. Analysis of the NSP4 gene divided porcine
      RVC strains into two clusters (the E1 genotype and the new E4 genotype, based on
      an 85% nucleotide sequence identity cutoff value). Our results indicate a degree
      of high genetic heterogeneity, not only in the variable VP7 and VP4 genes
      encoding the outer capsid proteins, but also in more-conserved genes encoding the
      inner capsid protein VP6 and the non-structural proteins NSP2, NSP4, and NSP5.
      This emphasizes the need for a whole-genome-sequence-based classification system.

PMID- 25951970
TI  - Prevalence and genetic diversity of noroviruses in adults with acute
      gastroenteritis in Huzhou, China, 2013-2014.
AB  - Norovirus (NoV) infection is the most common cause of nonbacterial acute
      gastroenteritis, which affects both adults and children. However, the molecular
      epidemiology of NoV in adults with acute gastroenteritis in China has not been
      investigated extensively. In this study, we investigated the occurrence of NoV
      infections and analyzed the genetic diversity of NoV in adults with acute
      gastroenteritis in Huzhou, China. A total of 796 fecal samples were collected
      from outpatients (>=16 years of age) between March 2013 and February 2014. Real
      time RT-PCR was performed to detect NoV genogroups I (GI) and II (GII). For
      genotyping, the capsid and RNA-dependent RNA polymerase (RdRp) genes were
      partially amplified and sequenced for phylogenetic analysis. NoVs were detected
      in 26.51% (211/796) of the specimens, with GII being predominant, representing
      96.20% of the NoV infections. At least nine genotypes were identified among GI
      and GII specimens, including GI.P2/GI.2, GI.P3/GI.3, GI.P4/GI.4, GII.Pe/GII.4
      Sydney_2012, GII.P12/GII.3, GII.P7/GII.6, GII.P16/GII.13, GII.Pe, and GII.Pg
      (RdRp only). This is the first report of a GII.P16/GII.13 recombinant virus in
      adults in China. GII.Pe/GII.4 Sydney_2012 was the most prevalent genotype and the
      only GII.4 variant identified during the study period. Our findings suggested
      that NoV was a common causative agent of acute gastroenteritis in adults in
      Huzhou, China. During the study period, the NoVs circulating in adults in Huzhou
      were predominantly GII.4 Sydney_2012 variants and GII NoV recombinants.

PMID- 25951971
TI  - Bufavirus in fecal specimens of patients with and without diarrhea in Thailand.
AB  - Bufavirus (BuV) was initially discovered in fecal samples from children with
      acute diarrhea. In this study, we determined the prevalence, distribution, and
      genotype(s) of BuV in Thailand. A total of 1,495 diarrheal and 741 non-diarrheal
      stool specimens were collected and analyzed. A portion of the NS1 gene of BuV was
      amplified by nested RT-PCR. Phylogenetic analysis was performed to classify the
      BuV strains found. We detected bufavirus (BuV) in diarrheal (4/1495; 0.27%) but
      not in non-diarrheal specimens (0/726). All four strains belonged to BuV genotype
      1. BuV could be detected in adults and children, but its role in causing acute
      diarrhea remains unclear.

PMID- 25951972
TI  - Experimental infection of inbred BALB/c and A/J mice with Massachusetts and
      Brazilian strains of infectious bronchitis virus (IBV).
AB  - The ability of avian coronaviruses to replicate in mice was investigated to
      investigate interspecies transmission. Two inbred mouse strains (BALB/c and A/J)
      with different genetic backgrounds were inoculated with the avian coronavirus
      strains Mass and BR-I and monitored for at least 10 days. Analysis of viral RNA,
      histopathological examinations, immunohistochemistry and serology were performed.
      After virus inoculation, neither clinical signs nor evident gross lesions were
      observed. Viral RNA, histopathological changes, and viral nucleoprotein were
      observed in the lung, trachea and sinus of all inoculated mice. Our study
      demonstrates the importance of elucidating the epidemiology of coronaviruses,
      including in rodents that are pests in poultry production. 

PMID- 25951973
TI  - Comparison of three magnetic-bead-based RNA extraction methods for detection of
      cucumber green mottle mosaic virus by real-time RT-PCR.
AB  - To determine the efficiency of RNA extraction methods based on magnetic beads,
      three different bead-based methods (one using silica-coated magnetic beads
      [SMNP], one using immunomagnetic beads conjugated to a specific antibody [IMB],
      and one using magnetic beads to nonspecifically adsorb virions [MNP]) were
      compared with the TRIzol method for the extraction of cucumber green mottle
      mosaic virus (CGMMV) RNA from cucumber leaves by real-time RT-PCR. The results
      indicated that the extraction efficiency of the SMNP method was 10 times higher
      than those of the IMB and MNP methods and 100 times higher than that of the
      TRIzol method. Therefore, the SMNP method could be considered for use in
      quarantine measures for the prevention and control of the disease caused by
      CGMMV. 

PMID- 25951974
TI  - Dominant-negative IKAROS enhances IL-3-stimulated signaling in wild-type but not
      BCR-ABL1(+) mouse BA/F3 cells.
AB  - Inactivating mutations in IKZF1, the gene that encodes the transcription factor
      IKAROS, are recurrent in poor-prognosis human B-cell leukemias, in which these
      mutations co-exist with BCR-ABL1 or other genetic changes that activate similar
      intracellular signaling pathways. However, little is known about the mechanism(s)
      by which loss of IKAROS activity may co-operate with BCR-ABL1 to transform
      lymphoid cells. To investigate this question, we used expression of a dominant
      negative isoform of IKAROS (IK6) to suppress endogenous IKAROS activity in the
      interleukin-3 (IL-3)-dependent mouse pro-B BA/F3 cell line and in an IL-3
      independent BCR-ABL1(+) derivative. We then used intracellular phospho-flow
      cytometry to assess the effects of BCR-ABL1 and IK6, alone and in combination, on
      the signaling state of the cells before and after their stimulation with IL-3.
      BCR-ABL1 and IK6 each produced a constitutively activated signaling phenotype and
      also enhanced the signaling responses of BA/F3 cells to IL-3. These effects,
      however, were neither equivalent nor additive, and IK6 alone was insufficient to
      confer the IL-3-independent growth characteristic of BCR-ABL1(+) BA/F3 cells. In
      addition to its effects on lymphoid cells, IK6 also induced constitutively
      activated signaling in a subset of myeloid leukemia cell lines. Together, these
      studies indicate an ability of IK6 to enhance intracellular signaling in both
      lymphoid and myeloid cells, but not to synergize with BCR-ABL1 in this model
      system. 

PMID- 25951975
TI  - Epidemiology and the bio-statistical theory of disease: a challenging
      perspective.
AB  - Christopher Boorse's bio-statistical theory (BST) of health and disease argues
      that the central discipline on which theoretical medicine relies is physiology.
      His theory has been much discussed but little has been said about its focus on
      physiology or, conversely, about the role that other biomedical disciplines may
      play in establishing a theoretical concept of health. Since at least the 1950s,
      epidemiology has gained in strength and legitimacy as an independent medical
      science that contributes to our knowledge of health and disease. Indeed, it not
      only provides important information about disease distribution and aetiology, but
      the risk-factor approach it employs seems to challenge BST's binary conception of
      health and disease. The objective of the article is to show, firstly, how
      important information deriving from descriptive and analytical epidemiology forms
      part of our contemporary medical concepts of health and disease, and secondly,
      that these elements are not taken into account by BST in a satisfactory way. The
      article's central contention, therefore, is that if the project of defining the
      theoretical concept of health is to be maintained, more importance should be
      accorded to the contribution made by epidemiology--alongside physiology--in
      defining health.

PMID- 25951976
TI  - BTG/Tob family members Tob1 and Tob2 inhibit proliferation of mouse embryonic
      stem cells via Id3 mRNA degradation.
AB  - The mammalian BTG/Tob family is a group of proteins with anti-proliferative
      ability, and there are six members including BTG1, BTG2/PC3/Tis21, BTG3/ANA,
      BTG4/PC3B, Tob1/Tob and Tob2. Among them, Tob subfamily members, specifically
      Tob1/Tob and Tob2, have the most extensive C-terminal regions. As previously
      reported, overexpression of BTG/Tob proteins is associated with the inhibition of
      G1 to S-phase cell cycle progression and decreased cell proliferation in a
      variety of cell types. Tob subfamily proteins have similar anti-proliferative
      effects on cell cycle progression in cultured tumor cells. An important
      unresolved question is whether or not they have function in rapidly proliferating
      cells, such as embryonic stem cells (ESCs). Tob1 and Tob2 were expressed
      ubiquitously in mouse ESCs (mESCs), suggesting a possible role in early embryonic
      development and mESCs. To address the above question and explore the possible
      functions of the Tob subfamily in ESCs, we established ESCs from different
      genotypic knockout inner cell mass (ICM). We found that Tob1(-/-), Tob2(-/-), and
      Tob1/2 double knockout (DKO, Tob1(-/-) & Tob2(-/-)) ESCs grew faster than wild
      type (WT) ESCs without losing pluripotency, and we provide a possible mechanistic
      explanation for these observations: Tob1 and Tob2 inhibit the cell cycle via
      degradation of Id3 mRNA, which is a set of directly targeted genes of BMP4
      signaling in mESCs that play critical roles in the maintenance of ESC properties.
      Together, our data suggest that BTG/Tob family protein Tob1 and Tob2 regulation
      cell proliferation does not compromise the basic properties of mESCs. 

PMID- 25951977
TI  - Secretion of PDGF isoforms during osteoclastogenesis and its modulation by anti
      osteoclast drugs.
AB  - In an attempt to identify secretory products of osteoclasts that mediate the
      coupling of bone formation to resorption, we found that along with osteoclast
      differentiation, PDGF-A gene expression increase occurred first, by 12 h after
      stimulation of bone marrow macrophages with M-CSF and RANKL, and peaked at 36 h.
      This was next followed by a progressive increase in PDGF-B gene expression until
      a peak at 60 h, when mature osteoclasts formed. Isoform-specific ELISA of the
      conditioned medium collected every 24 h revealed that all three of the isoforms
      of PDGF-AA, AB and BB were secreted, in this temporal order as differentiation
      proceeded. Their secretion was enhanced when osteoclasts were activated by
      placing them on dentin slices. The secretion of all three isoforms was decreased
      in cathepsin K-deficient osteoclasts compared with wild-type osteoclasts.
      Pharmacological inhibition of cathepsin K with odanacatib also inhibited the
      secretion of all three isoforms, as was also the case with alendronate treatment.
      The secretion of sphingosine-1-phosphate, which increased during
      osteoclastogenesis, was reduced from cathepsin K-deficient osteoclasts, and was
      inhibited by treatment with odanacatib more profoundly than with alendronate.
      Thus, all three isoforms of PDGF, which are secreted at distinct differentiation
      stages of osteoclasts, appear to have distinct roles in the cell-cell
      communication that takes place in the microenvironment of bone remodeling,
      especially from the osteoclast lineage to mesenchymal cells and vascular cells,
      thereby stimulating osteogenesis and angiogenesis.

PMID- 25951978
TI  - Syntheses, cholinesterases inhibition, and molecular docking studies of
      pyrido[2,3-b]pyrazine derivatives.
AB  - Cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE),
      have a role in cholinergic deficit which evidently leads to Alzheimer's disease
      (AD). Inhibition of cholinesterases with small molecules is an attractive
      strategy in AD therapy. This study demonstrates synthesis of pyrido[2,3
      b]pyrazines (6a-6q) series, their inhibitory activities against both
      cholinesterases, AChE and BChE, and molecular docking studies. The bioactivities
      data of pyrido[2,3-b]pyrazines showed 3-(3'-nitrophenyl)pyrido[2,3-b]pyrazine 6n
      a potent dual inhibitor among the series against both AChE and BChE with IC50
      values of 0.466 +/- 0.121 and 1.89 +/- 0.05 MUm, respectively. The analogues 3
      (3'-methylphenyl)pyrido[2,3-b]pyrazine 6c and 3-(3'-fluorophenyl)pyrido[2,3
      b]pyrazine 6f were found to be selective inhibition for BChE with IC50 values of
      0.583 +/- 0.052 MUm and AChE with IC50 value of 0.899 +/- 0.10 MUm, respectively.
      Molecular docking studies of the active compounds suggested the putative binding
      modes with cholinesterases. The potent compounds among the series could
      potentially serves as good leads for the development of new cholinesterase
      inhibitors. 

PMID- 25951979
TI  - Epidemiology of mumps and rubella in the Kingdom of Saudi Arabia: 2009-2011-
      Implications for immigration and travel.

PMID- 25951980
TI  - DNA polymerases: Biology, diseases and biomedical applications.

PMID- 25951981
TI  - Requirement of standardized ileal digestible valine to lysine ratio for 8- to 14
      kg pigs.
AB  - The objective was to define the Val requirement for weaned piglets in the context
      of reducing the dietary protein content. A dose-response experiment was conducted
      to estimate the standardized ileal digestible (SID) Val to Lys ratio required to
      support the optimum growth of post-weaned piglets. In this study, 96 pigs
      weighing 8 kg were allotted to one of six dietary treatments (16 pigs for each
      dietary treatment) and were housed individually. Diets were formulated to provide
      0.58, 0.62, 0.66, 0.70, 0.74 and 0.78 SID Val : Lys by adding graded levels of
      crystalline l-Val to the 0.58 SID Val : Lys diet. Lysine was sub-limiting and
      supplied 90% of the recommendation (10.95 g SID Lys/kg equal to 11.8 g/kg total
      Lys). Average daily feed intake (ADFI), average daily gain (ADG) and gain to feed
      ratio (G : F) were determined during a 14-day period of ad libitum feeding. Blood
      and urine samples were taken at the end of each week (day 7 and 14 of the
      experiment) 3 h after feeding the experimental diets. The maximum ADFI and ADG
      were obtained in pigs fed the 0.78 SID Val : Lys diet; it was not different from
      the results of pigs fed 0.70 SID Val : Lys diet. The highest G : F was obtained
      in pigs fed 0.70 SID Val : Lys. The plasma concentration of Val increased
      linearly (P<0.001) as the dietary SID Val : Lys increased. The increasing dietary
      Val : Lys also resulted in a linear increase in Cys (P<0.001) and a quadratic
      increase in Arg (P=0.003), Lys (P=0.05) and Phe (P=0.009). The plasma Gly showed
      a quadratic decrease (P=0.05) as the dietary Val : Lys increased. Neither plasma
      nor urinary urea to creatinine ratio was affected by treatment. The minimum SID
      Val : Lys required to maximize ADFI, ADG and G : F was estimated at 0.67 SID Val
      : Lys by a broken-line model, and at 0.71 SID Val : Lys by a curvilinear plateau
      model. The Val deficiency caused a reduction in ADFI, and Val supplementation
      above the requirement did not impair animal performance. In conclusion, 0.70 SID
      Val : Lys is suggested as the Val requirement for 8 to 14 kg individually housed
      pigs. 

PMID- 25951982
TI  - Allosteric therapies for lung cancer.
AB  - Allostery is a regulation at a distance by conveying information from one site to
      another and an intrinsic property of dynamic proteins. Allostery plays an
      essential role in receptor trafficking, signal transmission, controlled
      catalysis, gene turn on/off, or cell apoptosis. Allosteric mutations are
      considered as one of causes responsible for cancer development, leading to
      "allosteric diseases" by stabilizing an active or inactive conformation or
      changing the dynamic distribution of preexisting propagation pathways. The
      present article mainly focuses on the potential of allosteric therapies for lung
      cancer. Allosteric drugs may have several advantages over traditional drugs. The
      epidermal growth factor receptor mutations and signaling pathways downstream
      (such as PI3K/AKT/mTOR and RAS/RAF/MEK/ERK pathways) were suggested to play a key
      role in lung cancer and considered as targets of allosteric therapy. Some
      allosteric inhibitors for lung cancer-specific targets and a series of
      preclinical trials of allosteric inhibitors for lung cancer have been developed
      and reported. We expect that allosteric therapies will gain more attentions to
      develop combinatorial strategies for lung cancer and metastasis. 

PMID- 25951983
TI  - Global analyses of subtype- or stage-specific genes on chromosome 7 in patients
      with lung cancer.
AB  - Lung cancer is the most common cancer and becomes the leading cause of cancer
      mortality. Genetic and epigenetic alterations and variations are important to
      identify target genes in lung cancer and demonstrate the potential association of
      the chromosome 7 aberration with tumorigenesis. The present article integrated
      the independent and scattered global datasets to detect significant genes, co
      expressed, type-special and stage-special genes in lung cancer with a special
      focus on chromosome 7 with bioinformatics analysis methods. About 60, 214, 26, or
      49 up-regulated type-special genes, and 67, 35, 114, or 141 down-regulated type
      special genes were identified in adenocarcinoma (ADC), squamous cell carcinoma
      (SCC), large cell carcinoma (LCC) or small-cell lung cancer (SCLC), respectively.
      About 5, 2, 8, or 1 stage-specific genes were up-regulated, while 23, 8, 2, or 90
      stage-specific genes were down-regulated in ADC at stage I, II, III, or IV,
      respectively. Two stage-specific genes were significantly up-regulated in SCC at
      stage II, while 2 or 18 stage-specific genes in SCC at stage I or III were down
      regulated, respectively. Lung cancer prognostic prediction rates of subtype- or
      stage-specific genes were further evaluated. The present study globally analyzed
      and identified subtype- or stage-specific target genes of lung cancer on
      chromosome 7 by combining 16 GSE datasets for the first time, although there are
      still needs to furthermore validate the clinical values of those identified genes
      in a large population of patients with lung cancer. 

PMID- 25951984
TI  - Adjusting the Ion Permeability of Polyelectrolyte Multilayers through Layer-by
      Layer Assembly under a High Gravity Field.
AB  - The layer-by-layer (LbL) assembled multilayer has been widely used as good
      barrier film or capsule due to the advantages of its flexible tailoring of film
      permeability and compactness. Although many specific systems have been proposed
      for film design, developing a versatile strategy to control film compactness
      remains a challenge. We introduced the simple mechanical energy of a high gravity
      field to the LbL assembly process to tailor the multilayer permeability through
      adjusting film compactness. By taking poly(diallyldimethylammonium chloride)
      (PDDA) and poly{1-4[4-(3-carboxy-4-hydroxyphenylazo)benzenesulfonamido]-1,2
      ethanediyl sodium salt} (PAzo) as a model system, we investigated the LbL
      assembly process under a high gravity field. The results showed that the high
      gravity field introduced effectively accelerated the multilayer deposition
      process by 20-fold compared with conventional dipping assembly; the adsorption
      rate was positively dependent on the rotating speed of the high gravity equipment
      and the concentration of the building block solutions. More interestingly, the
      film compactness of the PDDA/PAzo multilayer prepared under the high gravity
      field increased remarkably with the growing rotational speed of the high gravity
      equipment, as demonstrated through comparisons of surface morphology, cyclic
      voltammetry curves, and photoisomerization kinetics of PDDA/PAzo multilayers
      fabricated through the conventional dipping method and through LbL assembly under
      a high gravity field, respectively. In this way, we have introduced a simple and
      versatile external form of mechanical energy into the LbL assembling process to
      improve film compactness, which should be useful for further applications in
      controlled ion permeability, anticorrosion, and drug loading. 

PMID- 25951985
TI  - Host responses associated with chronic staphylococcal mastitis in rabbits.
AB  - Staphylococcal infection causes substantial economic losses in commercial rabbit
      production systems, and is associated with a wide variety of lesions, including
      chronic suppurative mastitis, which mainly affects breeding females. Most chronic
      staphylococcal infections in rabbits are caused by the ST121 lineage of
      Staphylococcus aureus, although other less common lineages, such as ST96 can also
      be involved. The aims of the present study were to characterise the host immune
      response in natural cases of mastitis in rabbits caused by S. aureus, to evaluate
      any relationship between peripheral and local immunity and to investigate the
      effect of different S. aureus genotypes on these immune responses. Adult
      multiparous female rabbits that were affected with chronic staphylococcal
      mastitis (n = 204) were enrolled into the study. Histological and
      immunohistochemical evaluations of mammary glands were undertaken, as well as
      flow cytometric analyses of blood. S. aureus isolates from the mammary glands
      were identified by multilocus sequence typing. Differences in the number of
      infiltrating cells were detected, depending on the type of pathology, with more
      immature lesions demonstrating greater cellularity, characterised by greater
      numbers of T lymphocytes, macrophages and plasma cells. A relationship was seen
      between the cells in blood and mammary tissues, the most notable being the
      positive correlation between monocytes and tissue macrophages. When glands were
      infected with ST96 strains, fewer granulocytes (P < 0.01) and greater numbers of
      B cells (P < 0.01), T cells (P < 0.001), CD4(+) T cells (P < 0.001) and CD8(+) T
      cells (P < 0.01) were detected, compared with mammary glands that were infected
      by ST121 strains of S. aureus. 

PMID- 25951986
TI  - Survey of Campylobacter spp. in owned and unowned dogs and cats in Northern
      Italy.
AB  - Campylobacteriosis is among the most common bacterial causes of human
      gastroenteritis worldwide and pet ownership has been identified as a risk factor
      for Campylobacter infection in humans. Since canine and feline prevalence data
      are scarce in Italy, the present study was carried out to assess the prevalence,
      species distribution and risk factors for Campylobacter infection in dogs and
      cats under different husbandry conditions. Rectal swabs were collected from 171
      dogs (household pets, n = 100; shelter-housed dogs, n = 50; dogs from breeding
      kennels, n = 21) and 102 cats (household pets, n = 52; shelter-housed cats, n =
      21; free-roaming cats n = 29) in Northern Italy. Campylobacter was isolated from
      17% (n = 29) of dogs and 14.7% (n = 15) of cats. C. jejuni was the most common
      isolate in both species (Campylobacter spp.-positive dogs, 55.2%; Campylobacter
      spp.-positive cats, 53.3%), followed by C. upsaliensis (Campylobacter spp.
      positive dogs, 27.6%; Campylobacter spp.-positive cats, 40%). Other Campylobacter
      species were rarely detected, but included C. hyointestinalis subsp.
      hyointestinalis, C. lari and C. coli in dogs and C. coli and C. helveticus in
      cats. Among considered variables (sex, age, origin, diarrhoea, season of
      sampling), origin was identified as a risk factor for dogs, with shelter-housed
      dogs at higher risk than household dogs (odds ratio, 2.84; 95% CI 1.17, 6.92; P =
      0.021). The results of this study, particularly the high prevalence of C. jejuni
      in Campylobacter-positive animals, demonstrated that household and stray dogs and
      cats in Northern Italy might pose a zoonotic risk for humans. Moreover,
      biosecurity measures should be improved in dog shelters. 

PMID- 25951987
TI  - Mechanisms involved in quinolone resistance in Mycoplasma mycoides subsp. capri.
AB  - Mycoplasma mycoides subsp. capri is a causative agent of contagious agalactia in
      goats. In this study, M. mycoides subsp. capri mutants were selected for
      resistance to fluoroquinolones (norfloxacin, enrofloxacin and ciprofloxacin) by
      serial passes in broth with increasing concentrations of antibiotic. Mutations
      conferring cross-resistance to the three fluoroquinolones were found in the
      quinolone resistance determining regions of the four genes encoding DNA gyrase
      and topoisomerase IV. Different mutations in the DNA gyrase GyrA subunit suggest
      a different mechanism of inhibition between norfloxacin and the other tested
      fluoroquinolones. The presence of an adenosine triphosphate-dependent efflux
      system was suggested through the use of the inhibitor orthovanadate. 

PMID- 25951988
TI  - [(18)F]-fluorodeoxyglucose positron emission tomography of the cat brain: A
      feasibility study to investigate osteoarthritis-associated pain.
AB  - The objective of this pilot study was to investigate central nervous system (CNS)
      changes related to osteoarthritis (OA)-associated chronic pain in cats using
      [(18)F]-fluorodeoxyglucose ((18)FDG) positron emission tomography (PET) imaging.
      The brains of five normal, healthy (non-OA) cats and seven cats with pain
      associated with naturally occurring OA were imaged using (18)FDG-PET during a
      standardized mild anesthesia protocol. The PET images were co-registered over a
      magnetic resonance image of a cat brain segmented into several regions of
      interest. Brain metabolism was assessed in these regions using standardized
      uptake values. The brain metabolism in the secondary somatosensory cortex,
      thalamus and periaqueductal gray matter was increased significantly (P <= 0.005)
      in OA cats compared with non-OA cats. This study indicates that (18)FDG-PET brain
      imaging in cats is feasible to investigate CNS changes related to chronic pain.
      The results also suggest that OA is associated with sustained nociceptive inputs
      and increased activity of the descending modulatory pathways. 

PMID- 25951990
TI  - Cardiopulmonary arrest in a cat as a result of a suspected anaphylactic reaction
      to an intravenously administered iodinated contrast agent.

PMID- 25951991
TI  - Decreased TLR2 signal expression in peripheral blood mononuclear cell from
      patients with cryptococcal meningitis.
AB  - Toll-like receptors are the most important pattern recognition receptors that can
      recognize conserved molecular structures shared by large groups of pathogens.
      Here, the aim was to determine the expression and role of TLR2 in peripheral
      blood mononuclear cells (PBMCs) from patients with cryptococcal meningitis and
      healthy controls. TLR2 expression was measured using RT-PCR and western blotting.
      The role of TLR2 in cytokine production by PBMCs after Cryptococcus neoformans
      exposure was assessed in healthy controls prior to incubation with anti-TLR2.
      TLR2 mRNA and protein expression were both weaker in patients with cryptococcal
      meningitis than in healthy controls. Furthermore, pre-incubation of PBMCs from
      healthy donors with anti-TLR2 led to reduced expression of IFN-gamma and IL
      12p70, but not of IL-4 and IL-10, following C. neoformans stimulation. Our
      results suggest that impaired expression of TLR2 may be involved in defective
      host defense to C. neoformans through an attenuated Th1 response. 

PMID- 25951992
TI  - Surgical strategies for cutaneous neoplasm of the scalp. State of art.
AB  - AIM: Scalp reconstruction has always been a challenging task, in particular after
      oncological demolition and this article gives an overview on the state of the art
      in scalp reconstruction strategies. MATERIAL OF STUDY: We elaborated a systematic
      algorithm for scalp reconstruction based on location and size defects, presence
      or absence of periosteum, bone involvement, the quality of surrounding scalp
      tissue, the presence or absence of hair, location of the hairline, patient
      comorbidities and different procedures commonly used in plastic surgery. RESULTS:
      Our algorithm allows plastic surgeons to perform scalp reconstruction after the
      most devastating of defects. DISCUSSION: Successful reconstruction of the scalp
      requires careful preoperative planning and detailed knowledge of scalp anatomy,
      hair physiology, variety of available local tissue and plastic surgery procedures
      as well as synthetic substitutes or products provided by tissue engineering.
      CONCLUSION: However, the challenge today is to do so with excellent cosmetic
      results.

PMID- 25951994
TI  - Relation of Complementary-Alternative Medicine use with glomerular filtration
      rate and depression in patients with chronic kidney disease at predialysis stage.
AB  - AIM: Complementary and alternative medicine is a broad field of health including
      all health care practices and methods, and their accompanying theories and
      beliefs. In the present study, we aimed to examine the frequency of complementary
      alternative medicine use, and its relation with glomerular filtration rate and
      depression in patients with chronic kidney disease at predialysis stage. METHODS:
      A total of 1053 predialysis patients; 518 female and 535 male, that were followed
      up with chronic kidney disease for at least 3 months were enrolled into the
      study. Demographic features, biochemical parameters and findings of physical
      examination were recorded. Their compliance to diet, and knowledge about disease
      were questioned. Beck depression inventory and questionnaire regarding
      complementary-alternative medicine use were performed. RESULTS: The overall
      frequency of complementary-alternative medicine use was 40.3% . Total ratio of
      herbal products was 46%. Complementary-alternative medicine use was significantly
      more frequent in female or single patients, and patients that informed about
      chronic kidney disease or under strict diet (P = 0.007, P = 0.016, P = 0.02, P =
      0.016, respectively). When glomerular filtration rate of participants were
      considered, complementary-alternative medicine use was similar in different
      stages of kidney disease. Depression was observed in 41.9% of patients and
      significantly frequent in patients with alternative method use (P = 0.002).
      Depression score was higher as creatinine increases and glomerular filtration
      rate decreases (P = 0.002; r = 0.093). CONCLUSION: We determined that
      complementary-alternative medicine use gradually increases at predialysis stage
      as glomerular filtration rate decreases and there is a strict relation between
      complementary-alternative medicine use and depression or female gender. Disorder
      related stressors may lead to seeking of alternative methods.

PMID- 25951993
TI  - Striatal-enriched protein tyrosine phosphatase regulates the PTPalpha/Fyn
      signaling pathway.
AB  - The tyrosine kinase Fyn has two regulatory tyrosine residues that when
      phosphorylated either activate (Tyr(420)) or inhibit (Tyr(531)) Fyn activity.
      Within the central nervous system, two protein tyrosine phosphatases (PTPs)
      target these regulatory tyrosines in Fyn. PTPalpha dephosphorylates Tyr(531) and
      activates Fyn, while STEP (STriatal-Enriched protein tyrosine Phosphatase)
      dephosphorylates Tyr(420) and inactivates Fyn. Thus, PTPalpha and STEP have
      opposing functions in the regulation of Fyn; however, whether there is cross talk
      between these two PTPs remains unclear. Here, we used molecular techniques in
      primary neuronal cultures and in vivo to demonstrate that STEP negatively
      regulates PTPalpha by directly dephosphorylating PTPalpha at its regulatory
      Tyr(789). Dephosphorylation of Tyr(789) prevents the translocation of PTPalpha to
      synaptic membranes, blocking its ability to interact with and activate Fyn.
      Genetic or pharmacologic reduction in STEP61 activity increased the
      phosphorylation of PTPalpha at Tyr(789), as well as increased translocation of
      PTPalpha to synaptic membranes. Activation of PTPalpha and Fyn and trafficking of
      GluN2B to synaptic membranes are necessary for ethanol (EtOH) intake behaviors in
      rodents. We tested the functional significance of STEP61 in this signaling
      pathway by EtOH administration to primary cultures as well as in vivo, and
      demonstrated that the inactivation of STEP61 by EtOH leads to the activation of
      PTPalpha, its translocation to synaptic membranes, and the activation of Fyn.
      These findings indicate a novel mechanism by which STEP61 regulates PTPalpha and
      suggest that STEP and PTPalpha coordinate the regulation of Fyn. STEP61 ,
      PTPalpha, Fyn, and NMDA receptor (NMDAR) have been implicated in ethanol intake
      behaviors in the dorsomedial striatum (DMS) in rodents. Here, we report that
      PTPalpha is a novel substrate for STEP61. Upon ethanol exposure, STEP61 is
      phosphorylated and inactivated by protein kinase A (PKA) signaling in the DMS. As
      a result of STEP61 inhibition, there is an increase in the phosphorylation of
      PTPalpha, which translocates to lipid rafts and activates Fyn and subsequent
      NMDAR signaling. The results demonstrate a synergistic regulation of Fyn-NMDAR
      signaling by STEP61 and PTPalpha, which may contribute to the regulation of
      ethanol-related behaviors. NMDA, N-methyl-D-aspartate; PTPalpha, receptor-type
      protein tyrosine phosphatase alpha; STEP, STriatal-Enriched protein tyrosine
      Phosphatase.

PMID- 25951995
TI  - Rapid and Efficient Generation of Transgene-Free iPSC from a Small Volume of
      Cryopreserved Blood.
AB  - Human peripheral blood and umbilical cord blood represent attractive sources of
      cells for reprogramming to induced pluripotent stem cells (iPSCs). However, to
      date, most of the blood-derived iPSCs were generated using either integrating
      methods or starting from T-lymphocytes that have genomic rearrangements thus
      bearing uncertain consequences when using iPSC-derived lineages for disease
      modeling and cell therapies. Recently, both peripheral blood and cord blood cells
      have been reprogrammed into transgene-free iPSC using the Sendai viral vector.
      Here we demonstrate that peripheral blood can be utilized for medium-throughput
      iPSC production without the need to maintain cell culture prior to reprogramming
      induction. Cell reprogramming can also be accomplished with as little as 3000
      previously cryopreserved cord blood cells under feeder-free and chemically
      defined Xeno-free conditions that are compliant with standard Good Manufacturing
      Practice (GMP) regulations. The first iPSC colonies appear 2-3 weeks faster in
      comparison to previous reports. Notably, these peripheral blood- and cord blood
      derived iPSCs are free of detectable immunoglobulin heavy chain (IGH) and T cell
      receptor (TCR) gene rearrangements, suggesting they did not originate from B- or
      T- lymphoid cells. The iPSCs are pluripotent as evaluated by the scorecard assay
      and in vitro multi lineage functional cell differentiation. Our data show that
      small volumes of cryopreserved peripheral blood or cord blood cells can be
      reprogrammed efficiently at a convenient, cost effective and scalable way. In
      summary, our method expands the reprogramming potential of limited or archived
      samples either stored at blood banks or obtained from pediatric populations that
      cannot easily provide large quantities of peripheral blood or a skin biopsy. 

PMID- 25951996
TI  - SILA-421 activity in vitro against rifampicin-susceptible and rifampicin
      resistant Mycobacterium tuberculosis, and in vivo in a murine tuberculosis model.
AB  - Due to the emergence of multidrug-resistant and extensively drug-resistant
      tuberculosis (TB), there is an urgent need for new TB drugs or for compounds that
      improve the efficacy of currently used drugs. In this study, time-kill kinetics
      of SILA-421 as a single drug and in combination with isoniazid (INH), rifampicin
      (RIF), moxifloxacin (MXF) or amikacin (AMK) against Mycobacterium tuberculosis
      were assessed. Therapeutic efficacy in vivo in a mouse TB model was also studied.
      Further in vitro analysis was performed with a RIF-susceptible and RIF-resistant
      strains of M. tuberculosis. When used as a single drug, SILA-421 in vitro showed
      concentration-dependent and time-dependent bactericidal activity. SILA-421 also
      enhanced the activity of INH and RIF, resulting in synergy in the case of INH.
      Emergence of INH resistance following exposure to INH can be prevented by the
      addition SILA-421. SILA-421 had no additional value in combination with MXF or
      AMK. Furthermore, SILA-421 enhanced the activity of RIF towards a RIF-resistant
      strain and resulted in complete elimination of RIF-resistant mycobacteria.
      Unfortunately, in mice with TB induced by a Beijing genotype strain, addition of
      SILA-421 to an isoniazid-rifampicin-pyrazinamide regimen for 13 weeks did not
      result in enhanced therapeutic efficacy. 

PMID- 25951997
TI  - Conformational diversity of single-stranded DNA from bacterial repetitive
      extragenic palindromes: Implications for the DNA recognition elements of
      transposases.
AB  - Repetitive extragenic palindrome (REP)-associated tyrosine transposase enzymes
      (RAYTs) bind REP DNA domains and catalyze their cleavage. Genomic sequence
      analyses identify potential noncoding REP sequences associated with RAYT-encoding
      genes. To probe the conformational space of potential RAYT DNA binding domains,
      we report here spectroscopic and calorimetric measurements that detect and
      partially characterize the solution conformational heterogeneity of REP
      oligonucleotides from six bacterial species. Our data reveal most of these REP
      oligonucleotides adopt multiple conformations, suggesting that RAYTs confront a
      landscape of potential DNA substrates in dynamic equilibrium that could be
      selected, enriched, and/or induced via differential binding. Thus, the
      transposase-bound DNA motif may not be the predominant conformation of the
      isolated REP domain. Intriguingly, for several REPs, the circular dichroism
      spectra suggest guanine tetraplexes as potential alternative or additional RAYT
      recognition elements, an observation consistent with these REP domains being
      highly nonrandom, with tetraplex-favoring 5'-G and 3'-C-rich segments. In fact,
      the conformational heterogeneity of REP domains detected and reported here,
      including the formation of noncanonical DNA secondary structures, may reflect a
      general feature required for recognition by RAYT transposases. Based on our
      biophysical data, we propose guanine tetraplexes as an additional DNA recognition
      element for binding by RAYT transposase enzymes.

PMID- 25951998
TI  - Prolapse into the bile duct and expansive growth is characteristic behavior of
      mucinous cystic neoplasm of the liver: report of two cases and review of the
      literature.
AB  - Mucinous cystic neoplasm of the liver (MCN-L) is a very rare tumor whose detailed
      behavior is still unknown. We describe two cases of MCN-L that exhibited
      extremely interesting growth patterns, and discuss the characteristics of MCN-Ls.
      Both cases exhibited MCN-L that originated from the left hepatic lobe (Segment 4)
      and then prolapsed into the left hepatic duct and common bile duct, resulting in
      obstructive jaundice due to expansive growth. Endoscopic retrograde
      cholangiopancreatographies showed the characteristic oval-shaped filling defects
      in the bile ducts. Endoscopic ultrasound and intraductal ultrasound were useful
      for differentiating the tumors from stones, since multiple septal formations were
      observed inside the tumors. A literature search revealed that, over the past 10
      years, 15 cases of MCN-L (biliary cystadenomas with ovarian-like stroma) that
      showed expansive growth in the bile duct had been reported. Prolapse into the
      bile duct and expansive growth appear to be characteristic behavior of MCN-L. In
      the future, additional data on more cases needs to be collected to further
      elucidate MCN-L pathophysiology. 

PMID- 25951999
TI  - Expression of VEGF in neonatal urinary obstruction: does expression of VEGF
      predict hydronephrosis?
AB  - BACKGROUND: In animal studies, the inhibition of VEGF activity results in high
      mortality and impaired renal and glomerular development. Mechanical stimuli, like
      mechanical stretch in respiratory and circulatory systems, results in an elevated
      expression of VEGF. In animal models, the experimental urinary obstruction is
      associated with stretching of tubular cells and activations of the renin
      angiotensin system. This results in the upregulation of vascular endothelial
      growth factor (VEGF) and TNF-alfa. MATERIAL/METHODS: Tissue samples from urinary
      tract obstruction were collected and immunohistochemistry was performed in 14
      patients (average age: 7.1+/-4.1 years). The control histology group consisted of
      ureteropelvic junction tissue from 10 fetuses after midtrimester artificial
      abortion. The fetuses did not have any failure at ultrasound screening and
      pathological examination. The mean gestational age was 20.6 weeks of gestation
      (+/-2.2SD). Expression of VEGF was detected with immunohistochemistry method.
      RESULTS: Expression of VEGF was found in varying intensity in the submucosa and
      subserosa layers, but only in the test tissue (placental tissue). The tissue of
      the patients with urinary obstruction and the tissue of the fetal ureteropelvic
      junction without urinary obstruction were negative for expression of VEGF. The
      repeated examination showed negative cells and no color staining. CONCLUSIONS:
      The pressure due to congenital urogenital obstruction resulting in mechanical
      stress in cells did not increase the expression of VEGF in young children in our
      study. To find a correlation between urogenital tract obstruction and increased
      expression of VEGF, we need to perform more examinations because the connection
      may be of therapeutic significance.

PMID- 25952000
TI  - Anatomical Variations in the Pseudosylvian Fissure Morphology of Brachy-, Dolicho
      , and Mesaticephalic Dogs.
AB  - The purpose of the study is the following: (1) to anatomically characterize the
      right and the left pseudosylvian fissure (Psf) morphology; (2) to determine Psf
      variations between both hemispheres and between the three considered groups; and
      (3) to understand how these variations may influence brain surgery for dogs. Also
      we sought to determine whether there are any potential differences between brachy
      (B), dolicho- (D), and mesaticephalic (M) dogs. The present study considered 138
      brain hemispheres (N = 138) from 69 adult dog cadavers and used bregma
      craniometric point (b- the junction of coronal and sagittal cranial vault
      sutures) to characterize the Psf location on the superolateral brain surface. For
      statistical analysis, P values <0.05 were considered significant. The Psf was
      easily identified in all specimens at both hemispheres. Statistically significant
      differences for Psf width were registered between the groups, presenting M as the
      narrowest Psf regions. Fissure body length can be sorted in ascending order as D
      < M < B in both hemispheres, with the left Psf bigger than the right for all
      considered skulls. The greatest difference was registered in the B group with the
      left Psf 25.0% bigger than the right. Bregma has proved to be useful to appoint
      Psf location as more superior or inferior in the encephalic lateral surface,
      exhibiting in all groups the left Psf a superior position. For the groups the
      most inferior location was registered in M and the most superior in D.
      Understanding the Psf morphology and anatomical variations may provide important
      information to ensure safer intracranial procedures.

PMID- 25952001
TI  - Detection prevalence of H5N1 avian influenza virus among stray cats in eastern
      China.
AB  - Since 1997, more and more cases of the infectious H5N1 avian influenza virus
      (AIV) in humans have been reported all over the world but the transmission of
      H5N1 avian influenza virus to stray cats has been little demonstrated. The
      objective of this pilot investigation was to determine the prevalence of H5N1 AIV
      antibodies in stray cats in eastern China where is the dominant enzootic H5N1
      highly pathogenic avian influenza virus (HP AIV). A total of 1,020 nasal swab and
      1,020 serum samples were collected and tested. Evidence of HPAI H5N1 virus
      antibodies was present in two of the 1,020 serum samples that were positive by HI
      assay and NT assay, respectively. The results imply little transmission and that
      the Clade 2.3.2 HPAIV H5N1 infections in poultry did not significantly affect the
      rural animal shelters or suburban environment in eastern China. In future
      studies, these results can be used as baseline seroepidemiological levels for
      H5N1 AIV among cats in China.

PMID- 25952002
TI  - Roles of hypoxia, stem cells and epithelial-mesenchymal transition in the spread
      and treatment resistance of head and neck cancer.
AB  - Evidence from a wide range of studies indicates that hypoxia and the resulting
      cellular changes that are induced by HIF-1alpha lead to transcriptional up
      regulation of a diversity of genes that play major roles in modifying the
      cellular behaviour of head and neck squamous cell carcinoma (HNSCC). Although the
      mechanisms of cell adaptation to hypoxia are still not entirely clear, many
      studies relate hypoxia to enhanced survival of malignant cells. Stronger staining
      of tissue sections for HIF-1alpha correlates with poor prognostic outcomes, and
      the hypoxic tumour microenvironment generates selective pressures that enhance
      the ability of cancer stem cells (CSCs) to evade therapeutically induced cell
      death. The ability of hypoxia to further increase the resistance of CSCs to
      conventional therapeutics, whether they act by induction of apoptosis, senescence
      or autophagy, appears to limit therapeutic effectiveness of current agents. The
      demonstration of hypoxic induction of phenotypic changes leading to a
      subpopulation of CSCs with high motility, greater invasive properties and yet
      greater therapeutic resistance, complicates the issue still further. It appears
      that therapeutic interventions that allow manipulation of HIF-1alpha levels and
      responses, whether induced by hypoxia or by other mechanisms, could provide more
      effective actions of chemo- and radiotherapies at lower therapeutic dosages and
      thus result in better control of tumours with less toxicity to patients. 

PMID- 25952003
TI  - Characterization and cytocompatibility of a new injectable multiphasic bone
      substitute based on a combination of polysaccharide gel-coated OSPROLIFE((r))
      HA/TTCP granules and bone marrow concentrate.
AB  - The purpose of this study was to examine the in vitro cytocompatibility of a
      novel injectable multiphasic bone substitute (MBS) based on polysaccharide gel
      coated OSPROLIFE((r)) hydroxyapatite (HA)/tetracalcium phosphate (TTCP) granules
      combined with bone marrow concentrate (BMC). Polysaccharide gel-coated granules
      loaded in syringe were combined with BMC diluted in ionic crosslinking solution.
      The product was then maintained in culture to investigate the cytocompatibility,
      distribution, and osteogenic differentiation function of cells contained in the
      BMC. The in vitro cytocompatibility was assessed after 0, 24, and 96 h from the
      injectable MBS preparation using the LIVE/DEAD((r)) staining kit. The results
      highlighted that cells remained viable after combination with the polysaccharide
      gel-coated granules; also, viability was maintained over time. The distribution
      of the cells in the product, observed using confocal microscopy, showed viable
      cells immersed in the polysaccharide gel formed between the granules after ionic
      crosslinking. The mesenchymal stromal cells (MSC) contained in the injectable
      MBS, the basic elements for bone tissue regeneration, were able to differentiate
      toward osteoblasts, producing an osteogenic matrix as evidenced by alizarin red-s
      (AR-S) staining. In conclusion, we found that the injectable MBS may have the
      potential to be used as a bone substitute by applying a "one-step" procedure in
      bone tissue engineering applications. (c) 2015 Wiley Periodicals, Inc. J Biomed
      Mater Res Part B: Appl Biomater, 104B: 894-902, 2016.

PMID- 25952004
TI  - Development and characterization of a hydrogel containing silver sulfadiazine for
      antimicrobial topical applications.
AB  - Development and optimization of a hydrogel with impregnated silver sulfadiazine
      was pursued, for antimicrobial topical applications. The selected hydrogel
      exhibited a homogeneous appearance, with whitish colloration and devoid of any
      fractures or cracks. The content in impregnated silver sulfadiazine was within
      established limits (1%, w/w) with a standard deviation of up to 1.28%. The
      hydrogel presented a good characteristic in relation to release of the active
      antimicrobial principle, verified through swelling tests and antimicrobial
      activity. The swelling tests indicated a higher increase in weight during the
      first 6 h of contact with a moist environment, with a maximum value of 266.00 +/-
      0.81, and with maintenance of the original shape of the hydrogel. The impregnated
      silver sulfadiazine presented antimicrobial activity, as expected, indicating a
      prolonged release of the drug. The infrared spectra of the hydrogel with
      impregnated silver sulfadiazine indicated that the drug did not engage in any
      bonds with the polymeric matrix, which otherwise could have reduced its
      antimicrobial activity. The mechanical resistance tests produced good results,
      indicating that the hydrogels may be utilized in different locations of the human
      body with skin lesions.

PMID- 25952005
TI  - Association analysis revealed one susceptibility locus for vitiligo with immune
      related diseases in the Chinese Han population.
AB  - Generalized vitiligo is an autoimmune disease characterized by melanocyte loss,
      which results in patchy depigmentation of skin and hair, and is associated with
      an elevated risk of other immune-related diseases. However, there is no reported
      study on the associations between immune susceptibility polymorphisms and the
      risk of vitiligo with immune-related diseases. The aim of this study was to
      evaluate the potential influence of 10 single-nucleotide polymorphisms (SNPs) at
      18q21.31 (rs10503019), 4p16.1 (rs11940117), 3q28 (rs1464510), 14q12 (rs2273844),
      12q13.2 (rs2456973), 16q12.2 (rs3213758), 10q25.3 (rs4353229), 3q13.33
      (rs59374417), and 10p15.1 (rs706779 and rs7090530) on vitiligo with immune
      related diseases in the Chinese Han population. All SNPs were genotyped in 552
      patients with vitiligo-associated immune-related diseases and 1656 controls using
      the Sequenom MassArray system. Data were analyzed with PLINK 1.07 software. The C
      allele of rs2456973 at 12q13.2 was observed to be significantly associated with
      vitiligo-associated immune-related diseases (autoimmune diseases and allergic
      diseases) (P = 0.0028, odds ratio (OR) = 1.27). In subphenotype analysis, the
      rs2456973 C allele was also significantly associated with early-onset vitiligo by
      comparing with controls (P = 0.0001) and in the case-only analysis (P = 0.0114).
      We confirmed that 12q13.2 was an important candidate locus for vitiligo with
      immune-related diseases (autoimmune diseases and allergic diseases) and affected
      disease phenotypes with early onset.

PMID- 25952007
TI  - Parasympathetic reactivation in children: influence of two various modes of
      exercise.
AB  - PURPOSE: This study examined the effect of various modes of exercise on
      parasympathetic reactivation in children. METHODS: Twelve healthy boys
      volunteered for this study. Time domain measurement of heart rate variability in
      5 and 10 min and heart rate recovery (HRR) in 1 (HRR1) and 2 min (HRR2) were
      measured during recovery after incremental exercise tests by a 12-lead ECG.
      Incremental exercise tests were performed using either upper (arm cranking) or
      lower body (cycling) ergometers. RESULTS: The amounts of increase in RMSSD and
      PNN50 in 5 and 10 min of recovery were higher in arm cranking compared to
      cycling. HRR1 and HRR2 were significantly higher after arm cranking compared to
      cycling. CONCLUSIONS: These results suggest that parasympathetic reactivation is
      likely greater following exercises that use smaller muscle mass (arm cranking)
      rather than larger muscle mass (cycling) in healthy boys.

PMID- 25952006
TI  - Prediction of compensatory hyperhidrosis with botulinum toxin A and local
      anesthetic.
AB  - OBJECTIVE: Compensatory hyperhidrosis (CH) is one of the most problematic
      complications of sympathectomy, which occurs often and is hard to treat. A
      predictive procedure (PP) for CH can help patients experience compensatory
      sweating before sympathectomy to determine whether or not to perform
      sympathectomy. Our study aimed to evaluate the CH after the PP and sympathectomy
      in patients with primary palmar hyperhidrosis using multiple drugs. METHODS: We
      reviewed 83 patients who underwent a PP between July 2009 and August 2013 with
      primary palmar hyperhidrosis. In group A, we used levobupivacaine (n = 39). In
      group B, we used botulinum toxin A plus ropivacaine for the PP in group B (n =
      44). RESULTS: The CH rate after the PP was 44 % (group A) and 25 % (group B), and
      after sympathectomy 80 % (group A) and 75 % (group B). The prediction value
      between the PP and the sympathectomy was statistically significant in group A (p
      < 0.05). The positive prediction rate was 73 % and the negative prediction rate
      was 27 % in group A. CONCLUSIONS: Local anesthetic alone has a better predictive
      value. From our finding, patients should be made aware that CH after
      sympathectomy is less severe in 73 % of cases than that experienced in the PP.

PMID- 25952008
TI  - CO2 Fixation into Novel CO2 Storage Materials Composed of 1,2-Ethanediamine and
      Ethylene Glycol Derivatives.
AB  - A new CO2 fixation process into solid CO2 -storage materials (CO2 SMs) under mild
      conditions has been developed. The novel application of amine-glycol systems to
      the capture, storage, and utilization of CO2 with readily available 1,2
      ethanediamine (EDA) and ethylene glycol derivatives (EGs) was demonstrated.
      Typically, the CO2 SMs were isolated in 28.9-47.5 % yields, followed by extensive
      characterization using (13) C NMR, XRD, and FTIR. We found that especially the
      resulting poly-ethylene-glycol-300-based CO2 SM (PCO2 SM) product could be
      processed into stable tablets for CO2 storage; the aqueous PCO2 SM solution
      exhibited remarkable CO2 capturing and releasing capabilities after multiple
      cycles. Most importantly, the EDA and PEG 300 released from PCO2 SM were found to
      act as facilitative surfactants for the multiple preparation of CaCO3
      microparticles with nano-layer structure. 

PMID- 25952009
TI  - Latent semantic analysis cosines as a cognitive similarity measure: Evidence from
      priming studies.
AB  - In distributional semantics models (DSMs) such as latent semantic analysis (LSA),
      words are represented as vectors in a high-dimensional vector space. This allows
      for computing word similarities as the cosine of the angle between two such
      vectors. In two experiments, we investigated whether LSA cosine similarities
      predict priming effects, in that higher cosine similarities are associated with
      shorter reaction times (RTs). Critically, we applied a pseudo-random procedure in
      generating the item material to ensure that we directly manipulated LSA cosines
      as an independent variable. We employed two lexical priming experiments with
      lexical decision tasks (LDTs). In Experiment 1 we presented participants with 200
      different prime words, each paired with one unique target. We found a significant
      effect of cosine similarities on RTs. The same was true for Experiment 2, where
      we reversed the prime-target order (primes of Experiment 1 were targets in
      Experiment 2, and vice versa). The results of these experiments confirm that LSA
      cosine similarities can predict priming effects, supporting the view that they
      are psychologically relevant. The present study thereby provides evidence for
      qualifying LSA cosine similarities not only as a linguistic measure, but also as
      a cognitive similarity measure. However, it is also shown that other DSMs can
      outperform LSA as a predictor of priming effects. 

PMID- 25952010
TI  - Organ and tissue-dependent effect of resveratrol and exercise on antioxidant
      defenses of old mice.
AB  - BACKGROUND: Oxidative stress has been considered one of the causes of aging. For
      this reason, treatments based on antioxidants or those capable of increasing
      endogenous antioxidant activity have been taken into consideration to delay aging
      or age-related disease progression. AIM: In this paper, we determine if
      resveratrol and exercise have similar effect on the antioxidant capacity of
      different organs in old mice. METHODS: Resveratrol (6 months) and/or exercise
      (1.5 months) was administered to old mice. Markers of oxidative stress (lipid
      peroxidation and glutathione) and activities and levels of antioxidant enzymes
      (SOD, catalase, glutathione peroxidase, glutathione reductase and transferase and
      thioredoxin reductases, NADH cytochrome B5-reductase and NAD(P)H-quinone acceptor
      oxidoreductase) were determined by spectrophotometry and Western blotting in
      different organs: liver, kidney, skeletal muscle, heart and brain. RESULTS: Both
      interventions improved antioxidant activity in the major organs of the mice. This
      induction was accompanied by a decrease in the level of lipid peroxidation in the
      liver, heart and muscle of mice. Both resveratrol and exercise modulated several
      antioxidant activities and protein levels. However, the effect of resveratrol,
      exercise or their combination was organ dependent, indicating that different
      organs respond in different ways to the same stimulus. CONCLUSIONS: Our data
      suggest that physical activity and resveratrol may be of great importance for the
      prevention of age-related diseases, but that their organ-dependent effect must be
      taken into consideration to design a better intervention.

PMID- 25952011
TI  - In silico tools used for compound selection during target-based drug discovery
      and development.
AB  - INTRODUCTION: The target-based drug discovery process, including target
      selection, screening, hit-to-lead (H2L) and lead optimization stage gates, is the
      most common approach used in drug development. The full integration of in vitro
      and/or in vivo data with in silico tools across the entire process would be
      beneficial to R&D productivity by developing effective selection criteria and
      drug-design optimization strategies. AREAS COVERED: This review focuses on
      understanding the impact and extent in the past 5 years of in silico tools on the
      various stage gates of the target-based drug discovery approach. EXPERT OPINION:
      There are a large number of in silico tools available for establishing selection
      criteria and drug-design optimization strategies in the target-based approach.
      However, the inconsistent use of in vitro and/or in vivo data integrated with
      predictive in silico multiparameter models throughout the process is contributing
      to R&D productivity issues. In particular, the lack of reliable in silico tools
      at the H2L stage gate is contributing to the suboptimal selection of viable lead
      compounds. It is suggested that further development of in silico multiparameter
      models and organizing biologists, medicinal and computational chemists into one
      team with a single accountable objective to expand the utilization of in silico
      tools in all phases of drug discovery would improve R&D productivity.

PMID- 25952012
TI  - Sensitive detection of major food allergens in breast milk: first gateway for
      allergenic contact during breastfeeding.
AB  - Food allergy is recognized as a major public health issue, especially in early
      childhood. It has been hypothesized that early sensitization to food allergens
      maybe due to their ingestion as components dissolved in the milk during the
      breastfeeding, explaining reaction to a food, which has never been taken before.
      Thus, the aim of this work has been to detect the presence of the food allergens
      in breast milk by microarray technology. We produced a homemade microarray with
      antibodies produced against major food allergens. The antibody microarray was
      incubated with breast milk from 14 women collected from Fundacion Jimenez Diaz
      Hospital. In this way, we demonstrated the presence of major foods allergens in
      breast milk. The analysis of allergens presented in breast milk could be a useful
      tool in allergy prevention and could provide us a key data on the role of this
      feeding in tolerance induction or sensitization in children. 

PMID- 25952013
TI  - Cooling rate effects on thermal, structural, and microstructural properties of
      bio-hydroxyapatite obtained from bovine bone.
AB  - This article is focused on the study of cooling rate effects on the thermal,
      structural, and microstructural properties of hydroxyapatite (HAp) obtained from
      bovine bone. A three-step process was used to obtain BIO-HAp: hydrothermal,
      calcinations, and cooling. Calcined samples in a furnace and cooling in air (HAp
      CAir), water (HAp-CW), and liquid nitrogen (HAp-CN2), as well as an air cooled
      sample inside the furnace (HAp-CFAir), were studied. According to this study, the
      low cooling rate that was achieved for air cooled samples inside the furnace
      produce single crystal BIO-HAp with better crystalline quality; other samples
      exhibited polycrystalline structures forming micron and submicron grains.

PMID- 25951989
TI  - A multi-targeted approach to suppress tumor-promoting inflammation.
AB  - Cancers harbor significant genetic heterogeneity and patterns of relapse
      following many therapies are due to evolved resistance to treatment. While
      efforts have been made to combine targeted therapies, significant levels of
      toxicity have stymied efforts to effectively treat cancer with multi-drug
      combinations using currently approved therapeutics. We discuss the relationship
      between tumor-promoting inflammation and cancer as part of a larger effort to
      develop a broad-spectrum therapeutic approach aimed at a wide range of targets to
      address this heterogeneity. Specifically, macrophage migration inhibitory factor,
      cyclooxygenase-2, transcription factor nuclear factor-kappaB, tumor necrosis
      factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC
      chemokines are reviewed as important antiinflammatory targets while curcumin,
      resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are
      reviewed as low-cost, low toxicity means by which these targets might all be
      reached simultaneously. Future translational work will need to assess the
      resulting synergies of rationally designed antiinflammatory mixtures (employing
      low-toxicity constituents), and then combine this with similar approaches
      targeting the most important pathways across the range of cancer hallmark
      phenotypes. 

PMID- 25952015
TI  - Combined photocatalysis and membrane bioreactor for the treatment of feedwater
      containing thin film transistor-liquid crystal display discharge.
AB  - The nitrogen content of waste water generated by the thin film transistor-liquid
      crystal display (TFT-LCD) industry is not satisfactorily removed through the
      conventional aerobic-activated sludge process. In this study, the performance of
      three reactors - suspended type TiO2 membrane photoreactor (MPR), anoxic/oxic
      membrane bioreactor (AOMBR), and their combination (MPR-AOMBR) - was evaluated
      using feedwater containing TFT-LCD discharge. The parameters that maximized
      monoethanolamine (MEA) removal in the MPR were continuous ultraviolet (UV)
      irradiation and pH 11. Among the tested loadings, 0.1 g/l of TiO2 promoted MEA
      removal but degradation rate may further increase with photocatalyst
      concentration. The nitrified sludge recycle ratio R of the AOMBR was adjusted to
      1.5 to minimize the amount of nitrate in the effluent. The AOMBR greatly
      decreased chemical oxygen demand and MEA, but removed only 32.7% of tetramethyl
      ammonium hydroxide (TMAH). The MPR was configured as the pre-treatment unit for
      AOMBR, and the combined MPR-AOMBR has improved TMAH removal by 80.1%. The MPR
      bolstered performance by decomposing slowly biodegradable compounds, and had no
      negative effects on denitrification and carbon removal.

PMID- 25952014
TI  - Evolutionary Diagnosis of non-synonymous variants involved in differential drug
      response.
AB  - BACKGROUND: Many pharmaceutical drugs are known to be ineffective or have
      negative side effects in a substantial proportion of patients. Genomic advances
      are revealing that some non-synonymous single nucleotide variants (nsSNVs) may
      cause differences in drug efficacy and side effects. Therefore, it is desirable
      to evaluate nsSNVs of interest in their ability to modulate the drug response.
      RESULTS: We found that the available data on the link between drug response and
      nsSNV is rather modest. There were only 31 distinct drug response-altering (DR
      altering) and 43 distinct drug response-neutral (DR-neutral) nsSNVs in the whole
      Pharmacogenomics Knowledge Base (PharmGKB). However, even with this modest
      dataset, it was clear that existing bioinformatics tools have difficulties in
      correctly predicting the known DR-altering and DR-neutral nsSNVs. They exhibited
      an overall accuracy of less than 50%, which was not better than random diagnosis.
      We found that the underlying problem is the markedly different evolutionary
      properties between positions harboring nsSNVs linked to drug responses and those
      observed for inherited diseases. To solve this problem, we developed a new
      diagnosis method, Drug-EvoD, which was trained on the evolutionary properties of
      nsSNVs associated with drug responses in a sparse learning framework. Drug-EvoD
      achieves a TPR of 84% and a TNR of 53%, with a balanced accuracy of 69%, which
      improves upon other methods significantly. CONCLUSIONS: The new tool will enable
      researchers to computationally identify nsSNVs that may affect drug responses.
      However, much larger training and testing datasets are needed to develop more
      reliable and accurate tools.

PMID- 25952016
TI  - Synthesis of new metastable nanoalloys of immiscible metals with a pulse laser
      technique.
AB  - The generation of nanoalloys of immiscible metals is still a challenge using
      conventional methods. However, because these materials are currently attracting
      much attention, alternative methods are needed. In this article, we demonstrate a
      simple but powerful strategy for the generation of a new metastable alloy of
      immiscible metals. Au(1-x)Ni(x) 3D structures with 56 at% of nickel in gold were
      successfully manufactured by the pulsed laser irradiation of colloidal
      nanoparticles. This technology can be used for preparing different metastable
      alloys of immiscible metals. We hypothesise that this technique leads to the
      formation of alloy particles through the agglomerations of nanoparticles, very
      fast heating, and fast cooling/solidification. Thus, we expect that our approach
      will be applicable to a wide range of inorganic solids, yielding even new
      metastable solids that fail to be stable in the bulk systems, and therefore do
      not exist in Nature.

PMID- 25952017
TI  - Role of the gastrointestinal ecosystem in the development of type 1 diabetes.
AB  - A new emphasis has been put on the role of the gastrointestinal (GI) ecosystem in
      autoimmune diseases; however, there is limited knowledge about its role in type 1
      diabetes (T1D). Distinct differences have been observed in intestinal
      permeability, epithelial barrier function, commensal microbiota, and mucosal
      innate and adaptive immunity of patients and animals with T1D, when compared with
      healthy controls. The non-obese diabetic (NOD) mouse and the BioBreeding diabetes
      prone (BBdp) rat are the most commonly used models to study T1D pathogenesis.
      With the increasing awareness of the importance of the GI ecosystem in systemic
      disease, it is critical to understand the basics, as well as the similarities and
      differences between rat and mouse models and human patients. This review examines
      the current knowledge of the role of the GI ecosystem in T1D and indicates the
      extensive opportunities for further investigation that could lead to biomarkers
      and therapeutic interventions for disease prevention and/or modulation. 

PMID- 25952019
TI  - MICA: A fast short-read aligner that takes full advantage of Many Integrated Core
      Architecture (MIC).
AB  - BACKGROUND: Short-read aligners have recently gained a lot of speed by exploiting
      the massive parallelism of GPU. An uprising alterative to GPU is Intel MIC;
      supercomputers like Tianhe-2, currently top of TOP500, is built with 48,000 MIC
      boards to offer ~55 PFLOPS. The CPU-like architecture of MIC allows CPU-based
      software to be parallelized easily; however, the performance is often inferior to
      GPU counterparts as an MIC card contains only ~60 cores (while a GPU card
      typically has over a thousand cores). RESULTS: To better utilize MIC-enabled
      computers for NGS data analysis, we developed a new short-read aligner MICA that
      is optimized in view of MIC's limitation and the extra parallelism inside each
      MIC core. By utilizing the 512-bit vector units in the MIC and implementing a new
      seeding strategy, experiments on aligning 150 bp paired-end reads show that MICA
      using one MIC card is 4.9 times faster than BWA-MEM (using 6 cores of a top-end
      CPU), and slightly faster than SOAP3-dp (using a GPU). Furthermore, MICA's
      simplicity allows very efficient scale-up when multiple MIC cards are used in a
      node (3 cards give a 14.1-fold speedup over BWA-MEM). SUMMARY: MICA can be
      readily used by MIC-enabled supercomputers for production purpose. We have tested
      MICA on Tianhe-2 with 90 WGS samples (17.47 Tera-bases), which can be aligned in
      an hour using 400 nodes. MICA has impressive performance even though MIC is only
      in its initial stage of development. AVAILABILITY AND IMPLEMENTATION: MICA's
      source code is freely available at http://sourceforge.net/projects/mica-aligner
      under GPL v3. SUPPLEMENTARY INFORMATION: Supplementary information is available
      as "Additional File 1". Datasets are available at
      www.bio8.cs.hku.hk/dataset/mica.

PMID- 25952018
TI  - Topological control of the Caulobacter cell cycle circuitry by a polarized single
      domain PAS protein.
AB  - Despite the myriad of different sensory domains encoded in bacteria, only a few
      types are known to control the cell cycle. Here we use a forward genetic screen
      for Caulobacter crescentus motility mutants to identify a conserved single-domain
      PAS (Per-Arnt-Sim) protein (MopJ) with pleiotropic regulatory functions. MopJ
      promotes re-accumulation of the master cell cycle regulator CtrA after its
      proteolytic destruction is triggered by the DivJ kinase at the G1-S transition.
      MopJ and CtrA syntheses are coordinately induced in S-phase, followed by the
      sequestration of MopJ to cell poles in Caulobacter. Polarization requires
      Caulobacter DivJ and the PopZ polar organizer. MopJ interacts with DivJ and
      influences the localization and activity of downstream cell cycle effectors.
      Because MopJ abundance is upregulated in stationary phase and by the alarmone
      (p)ppGpp, conserved systemic signals acting on the cell cycle and growth phase
      control are genetically integrated through this conserved single PAS-domain
      protein. 

PMID- 25952021
TI  - Influence of three different preservative techniques on the mechanical properties
      of the ovine cortical bone.
AB  - PURPOSE: Preservative treatments are necessary for disinfection and long term
      storage when dealing with biological tissue. Freezing is a gold standard but
      infectious risk can only be eliminated by using chemical fluids that may alter
      the mechanical properties, depending on their composition. Therefore, we
      experimentally evaluated the influence of freezing and of two commonly used
      preservative fluids (formalin and alcohol) on the intrinsic mechanical properties
      of ovine cortical bone samples, compared to purely fresh samples. METHODS:
      Prismatic specimens were prepared from the sheep's metacarpal bones and were
      divided into four groups (fresh, fresh-frozen, formalin and alcohol). All samples
      underwent four-point-bending; fresh samples were tested immediately, preserved
      samples were tested after 14 days. Bending modulus, bending strength, yield
      strength and energy absorption for the elastic and plastic region were
      determined. RESULTS: Significant differences were found for the plastic energy
      absorption for formalin (-41%) and alcohol (+37%) preservation com- pared to
      fresh samples. Formalin preservation revealed embrittlement of the cortical bone
      samples and alcohol preservation revealed higher ability of plastic energy
      absorption. CONCLUSIONS: Our results indicate that freezing has no influence on
      the mechanical properties of the ovine cortical bone. Preservation with chemical
      fluids (formalin and alcohol) showed no influence on the elastic properties but
      it was observed for the ability of plastic energy absorption. Therefore, these
      methods seem to be suitable for preservation without evident altering of the
      elastic mechanical properties.

PMID- 25952020
TI  - Reliable femoral frame construction based on MRI dedicated to muscles position
      follow-up.
AB  - In vivo follow-up of muscle shape variation represents a challenge when
      evaluating muscle development due to disease or treatment. Recent developments in
      muscles reconstruction techniques indicate MRI as a clinical tool for the follow
      up of the thigh muscles. The comparison of 3D muscles shape from two different
      sequences is not easy because there is no common frame. This study proposes an
      innovative method for the reconstruction of a reliable femoral frame based on the
      femoral head and both condyles centers. In order to robustify the definition of
      condylar spheres, an original method was developed to combine the estimation of
      diameters of both condyles from the lateral antero-posterior distance and the
      estimation of the spheres center from an optimization process. The influence of
      spacing between MR slices and of origin positions was studied. For all axes, the
      proposed method presented an angular error lower than 1 degrees  with spacing
      between slice of 10 mm and the optimal position of the origin was identified at
      56 % of the distance between the femoral head center and the barycenter of both
      condyles. The high reliability of this method provides a robust frame for
      clinical follow-up based on MRI . 

PMID- 25952023
TI  - [New classification criteria for systemic sclerosis taking into account
      capillaroscopy].

PMID- 25952022
TI  - Expanded newborn screening by mass spectrometry: New tests, future perspectives.
AB  - Tandem mass spectrometry (MS/MS) has become a leading technology used in clinical
      chemistry and has shown to be particularly sensitive and specific when used in
      newborn screening (NBS) tests. The success of tandem mass spectrometry is due to
      important advances in hardware, software and clinical applications during the
      last 25 years. MS/MS permits a very rapid measurement of many metabolites in
      different biological specimens by using filter paper spots or directly on
      biological fluids. Its use in NBS give us the chance to identify possible
      treatable metabolic disorders even when asymptomatic and the benefits gained by
      this type of screening is now recognized worldwide. Today the use of MS/MS for
      second-tier tests and confirmatory testing is promising especially in the early
      detection of new disorders such as some lysosomal storage disorders, ADA and PNP
      SCIDs, X-adrenoleucodistrophy (X-ALD), Wilson disease, guanidinoacetate
      methyltransferase deficiency (GAMT), and Duchenne muscular dystrophy. The new
      challenge for the future will be reducing the false positive rate by using second
      tier tests, avoiding false negative results by using new specific biomarkers and
      introducing new treatable disorders in NBS programs.

PMID- 25952024
TI  - Whole-body MRI-DWI for assessment of residual disease after completion of therapy
      in lymphoma: A prospective multicenter study.
AB  - BACKGROUND: To assess the performance of whole-body MRI including diffusion
      weighted imaging (whole-body MRI-DWI) for the detection of residual disease after
      completion of treatment in lymphoma patients. METHODS: Twenty-six patients with
      lymphoma prospectively underwent whole-body MRI-DWI (1.5 Tesla MR) and 18F-fluoro
      2-deoxy-D-glucose positron emission tomography (FDG-PET)/computed tomography (CT)
      for posttreatment evaluation which were visually assessed. Apparent diffusion
      coefficient (ADC) and FDG-PET/CT standardized uptake value measurements were
      performed in all residual lesions. An unblinded expert panel reviewed all cases
      and determined the presence or absence of posttreatment residual disease using
      all available imaging (except for whole-body MRI-DWI), clinical, and
      histopathological information with a follow-up of at least 6 months. The
      performance of whole-body MRI-DWI was compared with this panel reference
      standard. RESULTS: Five of 26 patients were diagnosed with residual disease.
      Sensitivity and specificity for detection of residual disease with whole-body MRI
      DWI were 100% and 62%, respectively. By ROC analysis, the optimal threshold of
      ADC was 1.21 * 10(-3) mm(2) /s with sensitivity and specificity of 100% and
      91.7%, respectively. CONCLUSION: Our initial results suggest that visual whole
      body MRI-DWI analysis has a very good sensitivity for detecting viable residual
      lesions after completion of therapy but lacks specificity. ADC measurements could
      potentially increase the specificity of whole-body MRI.

PMID- 25952025
TI  - Au-nanocrystals-decorated delta-MnO2 as an efficient catalytic cathode for high
      performance Li-O2 batteries.
AB  - A Li-O2 battery works based on the reversible formation and decomposition of
      Li2O2, which is insulating and highly reactive. Designing a catalytic cathode
      capable of controlling Li2O2 growth recently became a challenge to overcome this
      barrier. In this work, we present a new design of catalytic cathode by growing
      porous Au/delta-MnO2 electrocatalyst directly on a conductive substrate. We found
      that Au/delta-MnO2 can catalyze the directed growth of Li2O2 into a thin/small
      form, only inside porous delta-MnO2, and along the surface of delta-MnO2 sheets.
      We proposed the catalytic mechanism of Au/delta-MnO2, where Au plays a critical
      role in catalyzing the nucleation, crystallization and conformal growth of Li2O2
      on delta-MnO2 sheets. Li-O2 batteries with an Au/delta-MnO2 catalytic cathode
      showed excellent electrochemical performance due to this favorable Li2O2 growth
      habit. The battery yielded a high capacity of 10,600 mA h g(-1) with a low
      polarization of 0.91 V at 100 mA g(-1). Superior cycling stability could be
      achieved in both capacity-limited (500 mA h g(-1), 165 times at 400 mA g(-1)) and
      unlimited (ca. 3000 mA h g(-1), 50 cycles at 800 mA g(-1)) modes.

PMID- 25952026
TI  - When a funnel becomes a martini glass: Adolescent performance on the Boston
      Naming Test.
AB  - The Boston Naming Test (BNT), a component of the Boston Diagnostic Aphasia
      Examination, is often used by neuropsychologists to assess confrontation naming.
      Research indicates that performance on the BNT is impacted by a variety of
      factors including age, gender, measured intelligence, educational attainment,
      vocabulary knowledge, level of acculturation, and ethnicity. Extant normative
      data are available for adults and for younger children; however, descriptive data
      are lacking for neurologically intact adolescents. The current study obtained
      normative data for the BNT, second edition in 15- to 18-year-old adolescents. The
      sample included 200 participants (100 male, 100 female) who were screened to
      exclude individuals with neurologic, psychiatric, or academic difficulties. There
      were no statistically significant differences in BNT scores based on gender, age,
      or grade. Normative means and standard deviations, collapsed across age and
      gender, are provided. The relationship of the current data to existing child and
      adult norms, as well as the clinical utility of examining individual item
      responses for the BNT in this sample are addressed. 

PMID- 25952027
TI  - Comparative study of enzymatic antioxidants in muscle of elasmobranch and teleost
      fishes.
AB  - Exercise may cause an imbalance between pro-oxidants and antioxidants. In
      skeletal muscle, oxygen flow can increase considerably during vigorous exercise.
      The antioxidant system in athletes contributes to neutralize the concomitant rise
      in reactive oxygen species (ROS) production. The objective of this study was to
      compare the antioxidant system in muscle of three species of elasmobranchs and
      teleosts, considering differences in swimming capacity among species within each
      group and evolutionary differences between the two groups. Muscle samples were
      collected from elasmobranchs (Isurus oxyrinchus, Prionace glauca, Mustelus
      henlei) and teleosts (Totoaba macdonaldi, Kajikia audax and Coryphaena hippurus)
      in the coast of the Baja California peninsula, Mexico. The enzymatic activity of
      superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx),
      glutathione reductase (GR) and glutathione S-transferase (GST) was determined by
      spectrophotometry. The activity of the antioxidant enzymes CAT, GPx and GST was
      higher in elasmobranchs, as a group, than in teleosts. In fish species with high
      swimming capacities, P. glauca, K. audax and C. hippurus, antioxidant enzyme
      activity was higher in comparison with species with lower swimming capacities, M.
      henlei and T. macdonaldi. It is possible that antioxidant enzymes, particularly
      SOD, GPx and GST, contribute to avoidance of oxidative damage in teleost and
      elasmobranch species with higher swimming capacities. The antioxidant enzyme
      activities in fish appear to depend mainly on their swimming capacity and life
      style rather than the evolutionary group (elasmobranchs, teleosts). 

PMID- 25952028
TI  - Peptide self-assembly triggered by metal ions.
AB  - Through their unique and specific interactions with various metal ions, naturally
      occurring proteins control structures and functions of many biological processes
      and functions in organisms. Inspired by natural metallopeptides, chemists have
      developed artificial peptides which coordinate with metal ions through their
      functional groups either for introducing a special reactivity or for constructing
      nanostructures. However, the design of new coordination peptides requires a deep
      understanding of the structures, assembly properties, and dynamic behaviours of
      such peptides. This review briefly discusses strategies of peptide self-assembly
      induced by metal coordination to different natural and non-natural binding sites
      in the peptide. The structures and functions of the obtained aggregates are
      described as well. We also highlight some examples of a metal-induced peptide
      self-assembly with relevance to biotechnology applications. 

PMID- 25952031
TI  - Title of news article on zoledronic acid and bone density was misleading.

PMID- 25952029
TI  - Candida spp. and gingivitis in children with nephrotic syndrome or type 1
      diabetes.
AB  - BACKGROUND: Diabetes and Nephrotic syndrome (NS) promote plaque-related
      gingivitis and yeast-like fungal infections. The study assesses the impact of
      Candida spp. and general disease- or treatment-related factors on plaque-related
      gingivitis severity in children and adolescents with Nephrotic syndrome
      /diabetes. METHODS: Body mass index (BMI), BMI standard deviation score, and oral
      cavity (Plaque Index--PLI, Gingival Index--GI, mucosa status, presence and
      Candida enzymatic activity) were assessed in 96 patients (32 with NS: 30-
      immunosuppressive treatment, 35--type 1 diabetes, and 29 generally healthy),
      aged; 3-18 years. Laboratory included cholesterol and triglyceride measurements;
      in diabetic subjects- glycated haemoglobin, in NS: total protein, albumin,
      creatinine, haemoglobin, haematocrit, white cell count, urinary protein
      excretion. Medical records supplied information on disease duration and
      treatment. A statistical analysis was performed; Kendall Tau coefficient, chi
      square test, t-test, and multiple regression analysis ( P < 0.05). RESULTS:
      Candida spp. often occurred in healthy patients, but oral candidiasis was found
      only in the NS and diabetes groups (9.37% and 11.43%). Gingivitis occurred more
      frequently in patients with NS/diabetes. Gingivitis severity was correlated with
      PLI, age, and yeast enzyme activity in NS--to with immunosuppressive treatment
      with >1 drug, drug doses, treatment duration, lipid disorders, and BMI; in
      diabetes, with blood glucose and glycated haemoglobin >8%. CONCLUSION: Poor
      hygiene control is the main cause of gingivitis. Gingivitis severity is most
      likely related to age, lipid disorders and increase in body mass. Candida spp.,
      in uncompensated diabetes and in those using immunosuppressive treatment, might
      intensify plaque-related gingivitis.

PMID- 25952030
TI  - Interactive effects of a common gamma-glutamyltransferase 1 variant and low high
      density lipoprotein-cholesterol on diabetic macro- and micro-angiopathy.
AB  - BACKGROUND: We investigated the clinical relevance of a common variant,
      rs4820599, in the gamma-glutamyltransferase (GGT)1 gene, associated with the
      serum GGT level, in Japanese type 2 diabetes mellitus (T2DM) subjects. METHODS:
      We conducted a retrospective longitudinal study (4.9 +/- 2.5 years) including 352
      T2DM patients (T2DM subjects) and a cross-sectional study including 796 health
      screening program participants (general subjects). A real-time TaqMan allelic
      discrimination assay was used to identify the genotypes. Risk factors for a high
      brachial-ankle pulse wave velocity (baPWV) (>=1750 cm/sec) or diabetic
      retinopathy (DR) were determined using a generalized estimating equations
      approach, receiver operating characteristic (ROC) analysis or Cox proportional
      hazards model, etc. RESULTS: The frequency of the GGT1 G allele was 20.8% in the
      T2DM subjects, and no associations were found between the GGT1 genotype and risk
      of T2DM. The mean log GGT values in the T2DM and general subjects were
      significantly higher among G allele carriers than non-carriers. The G allele and
      a low HDL-C level were identified to be risk factors for a high baPWV in the T2DM
      subjects [odds ratio (OR) 1.80, P = 0.008; OR 1.71, P = 0.03; respectively), and
      a significant interactive effect between these factors was found on the risk of a
      high baPWV and DR. The HDL-C level at baseline was a significant predictor of a
      high baPWV only in G allele carriers according to the ROC analysis. This result
      regarding baPWV in the T2DM subjects was replicated in the general population.
      Meanwhile, the GGT1 genotype was not associated with the risk of DR, although it
      affected the principal factors involved in the risk of DR, and a low HDL-C level
      was also found to be a risk factor for DR only in G allele carriers. CONCLUSIONS:
      We herein describe for the first time the significant interactive effects of the
      GGT1 G allele and a low HDL-C level on a high baPWV and DR. These findings may
      encourage future clinical trials comparing the efficacy of agents increasing the
      HDL-C levels among the GGT1 genotypes. However, well-designed studies in larger
      cohorts are needed to confirm our results.

PMID- 25952032
TI  - Antepartum Mastitis: A Rare Occurrence.
AB  - Puerperal or lactational mastitis is an inflammatory condition of the breast that
      is commonly encountered in breastfeeding mothers. It occurs most commonly in the
      postpartum period, generally in the first 6 weeks of breastfeeding. In contrast,
      antepartum mastitis is an uncommon condition, and if not treated adequately, it
      may be complicated by the formation of a breast abscess. The authors present a
      case of a 24-year-old, second gravida mother who developed unilateral antepartum
      mastitis with abscess formation at 34 weeks of gestation, which was initially
      treated with antibiotics and surgical drainage. However, her symptoms persisted
      over the next 2 weeks, and she was referred to the authors' institution, where
      she was managed with antibiotics and surgical drainage after delivering a healthy
      near-term infant. The abscesses healed completely 2 months later, with sequelae
      of residual scarring and a nonprotractile nipple. The authors wish to emphasize
      that health care providers should be aware of the occurrence of mastitis in the
      antepartum period. Early recognition with adequate treatment of mastitis is the
      key to avoiding complications, and this will prevent lactation issues and also
      reduce morbidity in the mother and neonate. 

PMID- 25952033
TI  - Re: Generalizability of trial results to elderly medicare patients with advanced
      solid tumors.

PMID- 25952035
TI  - Filaggrin-2 barrier protein inversely varies with skin inflammation.

PMID- 25952036
TI  - Comparison of the effects of intensive insulin treatment modalities on
      cardiovascular biomarkers in type 1 diabetes mellitus.
AB  - AIM: To evaluate effects of intensive insulin treatment modalities on
      cardiovascular biomarkers in patients with type 1 diabetes mellitus (T1DM).
      MATERIALS AND METHODS: A total of 25 patients with T1DM receiving intensive
      insulin therapy either in the form of continuous insulin pump (IP group; n=13) or
      as multiple daily injections (MDI group; n=12) and 13 controls (control group,
      n=13) were included. Data on demographics, anthropometrics, diabetes history, and
      laboratory findings including glycemic and lipid parameters, and cardiovascular
      biomarkers [C-reactive protein (mg/dL), homocysteine (MUmol/L), fibrinogen
      (mg/dL), oxidized LDL (ng/dL), PAI-1 (ng/mL), MCP-1 (pg/mL) and VEGF (pg/mL)]
      were recorded in each group. Correlation of cardiovascular biomarkers to other
      parameters was also evaluated in T1DM patients. RESULTS: Apart from significantly
      higher mean (SD) values for HbA1c [6.1 (0.3) vs. 5.6 (0.5)% (43 (3) vs. 38 (5)
      mmol/mol), p<0.05)] and HDL-cholesterol [71.5 (13.6) vs. 58.2 (10.8), p<0.01) in
      the IP than in the MDI group, no significance difference was noted between
      insulin treatment modalities as well as between patient and control groups in
      terms of demographic, anthropometric and laboratory parameters. Negative
      correlation of MCP-1 to treatment duration (r=-0.615, p=0.025), and HDL-c to CRP
      (r=-0.685, p=0.010) and VEGF (r=-0.678, p=0.011) was noted in IP group, whereas
      positive correlation of PAI-1 to diabetes age (r=0.805, p=0.002) and treatment
      duration was noted in MDI group. CONCLUSION: Our findings in a cohort of T1DM
      patients with optimal glycemic control revealed that intensive insulin therapy
      was not associated with an increase in atherosclerotic markers in T1DM,
      regardless of whether continuous IP infusion or MDIs was administered.

PMID- 25952037
TI  - Prevalence of glucose intolerance at 6 weeks postpartum in Indian women with
      gestational diabetes mellitus.
AB  - AIMS: Women with a history of gestational diabetes mellitus (GDM) have an
      increased risk for future glucose intolerance, and should be followed up with
      subsequent screening for the development of diabetes or pre-diabetes at 6-12
      weeks postpartum. We studied the prevalence of glucose intolerance at 6 weeks
      postpartum in Indian women with GDM diagnosed according to ADA criteria.
      MATERIALS AND METHODS: This longitudinal study, conducted at a tertiary care
      centre, included 75 Asian-Indian women aged >=18 years, with a diagnosis of GDM
      (as per ADA criteria), who were referred to the Endocrine Department at
      Indraprastha Apollo Hospital, Delhi. A 2-h 75 g oral glucose tolerance test
      (OGTT) was performed at 6 weeks postpartum. RESULTS: Out of the 75 women who had
      GDM and were recommended an OGTT at 6 weeks postpartum, 17.3% did not return for
      the test. Out of 62 women, one-third (33.8%) developed an abnormal OGTT at 6
      weeks postpartum, while 66.1% had reverted to normal glucose tolerance. Impaired
      fasting glucose (IFG) was seen in 14.5%, 4.8% had impaired glucose tolerance
      (IGT), 8% had both IFG and IGT, and 6.4% had overt type 2 diabetes. CONCLUSION:
      Our study emphasizes the need for compulsory follow up OGTT for women with GDM in
      our part of the world in view of ethnicity and prevailing socio-cultural factors.

PMID- 25952038
TI  - Association of adipokines with metabolic disorders in patients with
      schizophrenia: Results of comparative study with mental healthy cohort.
AB  - AIM: The role of adipose tissue hormones, adipokines, in formation of metabolic
      disorders in schizophrenia is not fully understood. The aim was to investigate
      the association of leptin and adiponectin plasma levels with metabolic parameters
      in antipsychotic treated patients with schizophrenia and in the group of age,
      gender and body mass index matched mental healthy persons. METHODS: One hundred
      patients with diagnosis of schizophrenia, who took antipsychotic medication, and
      equal number of control subjects, were enrolled for cross-sectional evaluation.
      Fasting blood plasma levels of glucose, lipids, insulin, adiponectin, leptin
      concentrations and insulin resistance HOMA index were determined. RESULTS: In
      both groups plasma leptin concentration positively correlated with body mass
      index, insulin plasma level and HOMA index, while adiponectin level had negative
      correlations with adiposity measures and positive associations with high density
      lipoprotein cholesterol content. At the same time, in schizophrenia group, but
      not in control subjects, leptin level positively associated with cholesterol and
      triglycerides concentrations and adiponectin negatively correlated with plasma
      insulin content, HOMA index and triglycerides levels. After controlling for
      confounders significant correlations remained for leptin concentration with HOMA
      index and plasma triglycerides level in schizophrenic patients and for
      adiponectin concentration with plasma high density lipoprotein cholesterol
      concentrations in both studied groups. CONCLUSIONS: Both adipokines associate
      with metabolic parameters in antipsychotic treated patients with schizophrenia.
      Leptin can play more specific role in pathogenesis of metabolic syndrome in
      schizophrenic persons than in mental healthy subjects.

PMID- 25952039
TI  - Prevalence of metabolic syndrome in adult population in Shiraz, southern Iran.
AB  - AIM: Metabolic syndrome (MSx) is associated with increased risk of cardiovascular
      diseases and type 2 diabetes mellitus. This study evaluated the prevalence of MSx
      in adult population in Shiraz, southern Iran. METHODS: In a cross-sectional study
      conducted between October 2012 and April 2013, using a simple random sampling
      method, 377 adults aged more than 20 years who were invited for periodic health
      examinations to Petroleum Industry Health Organization Polyclinic, a general
      health care center, Shiraz, southern Iran, were studied. The revised National
      Cholesterol Education Program-Adult Treatment Panel III was used for the
      diagnosis of MSx. RESULTS: The participants included 190 women and 187 men with a
      mean+/-SD age of 43.8+/-11.0 (range: 20-86) years. Of 377 participants, 101
      (26.8%, 95% CI: 22.3-31.3%) had MSx. The prevalence in men (16.6%) was
      significantly (p<0.001) lower than that in women (36.8%). The prevalence
      increased by almost 15% with each decade of life (p<0.001). CONCLUSION: The
      prevalence of MSx in our population, particularly in women, is high. Strategies
      should be planned to prevent the increasing prevalence of MSx in our country.

PMID- 25952040
TI  - The long-term outcome of the refractive error in children with hypermetropia.
AB  - PURPOSE: The purpose of this study was to investigate the long-term outcome of
      high hypermetropic refractive errors in childhood. METHODS: We retrospectively
      reviewed data from the clinical records of 164 children with spherical equivalent
      (SE) hypermetropic refractive errors in three medical centers collected over 29
      years. Refractive errors between +1.00 and +3.00 diopter (D) on initial
      examination were classified as mild hypermetropia and those +5.00 D or greater
      were classified as high hypermetropia. The four variables studied were, age,
      refractive error, strabismus, and gender. The rate of reduction in hypermetropic
      refractive error was calculated over time in years. We identified subgroups
      according to age, gender, and initial refractive error. RESULTS: Seventy-eight
      children with high hypermetropia and 86 children with mild hypermetropia were
      studied. High hypermetropia was detected at a mean age of 3.3 years, while mild
      hypermetropia was detected at a mean 4 years of age. The mean follow-up was 6.6
      years for high hypermetropia and 6.4 years for mild hypermetropia. Over the
      follow-up period, children in all subgroups tended to reduce their refractive
      errors. The reduction in refraction power was small for both mild and high
      hypermetropic refractive errors. Amblyopia in the high hypermetropia group was
      more common and more refractory to treatment. CONCLUSIONS: Most children with
      hypermetropia of less than +3.00 D experience a reduction in hyperopic refractive
      error over time and will outgrow any need for corrective lenses. Children with
      hyperopia greater than +5.00 D will not experience a significant reduction in the
      power of the refractive error.

PMID- 25952042
TI  - The effect of professional-led guideline workshops on clinical practice for the
      management of patent ductus arteriosus in preterm neonates in Japan: a controlled
      before-and-after study.
AB  - BACKGROUND: Clinical guidelines assist physicians to make decisions about
      suitable healthcare. We conducted a controlled before-and-after study to
      investigate the impact of professional-led guideline workshops for patent ductus
      arteriosus (PDA) management on physicians' clinical practices, discharge
      mortality, and associated morbid conditions among preterm neonates. METHODS: We
      recruited physicians practicing at two neonatal intensive care units (NICUs) in
      Japan and used the data of all neonates weighing less than or equal to 1,500 g
      admitted to 90 NICUs (2 intervention NICUs and 88 control NICUs) in the Neonatal
      Research Network of Japan from April 2008 to March 2010. We held 1-day workshops
      for physicians on PDA clinical practice guidelines at the two intervention NICUs.
      Physicians' skills assessed by confidence rating (CR) scores and the Sheffield
      Peer Review Assessment Tool (SPRAT) were compared between pre- and post-workshop
      month at the intervention NICUs using Wilcoxon signed-rank tests. Neonatal
      discharge mortality and morbidity were compared between pre- and post-workshop
      year at both the intervention and control NICUs using multivariable regression
      analyses adjusting for potential confounders. RESULTS: Fifteen physicians were
      included in the study. Physicians' CR scores (2.14 vs. 2.47, p = 0.02) and SPRAT
      (4.14 vs. 4.50, p = 0.05) in PDA management improved after the workshops. The
      analyses of neonatal outcomes included 294 and 6,234 neonates in the intervention
      and control NICUs, respectively. Neonates' discharge mortality declined sharply
      at the intervention NICUs (from 15/146 to 5/148, relative risk reduction -0.67;
      adjusted odds ratio 0.30, 95% confidence interval 0.10 to 0.89) during the post
      workshop period. The mortality reduction was much greater than that in the
      control NICUs (from 207/3,322 to 147/2,912, relative risk reduction -0.19;
      adjusted odds ratio 0.75, 95% confidence interval 0.59 to 0.95), although the
      difference between the intervention and control NICUs were not statistically
      significant. CONCLUSIONS: Overall, physicians' confidence in PDA management
      improved after attending guideline workshops. Face-to-face workshops by guideline
      developers can be a useful strategy to improve physicians' PDA management skills
      and, thereby, might reduce PDA-associated mortality in preterm neonates.

PMID- 25952041
TI  - Retinal vessel oxygen saturation and vessel diameter in retinitis pigmentosa at
      various ages.
AB  - PURPOSE: This study was conducted to determine whether oxygen saturation and
      retinal blood vessel diameter are affected by retinitis pigmentosa (RP) at
      various ages. METHODS: Relative oxygen saturation was measured in retinal blood
      vessels in 68 RP patients and 136 normal subjects using the Oxymap T1 retinal
      oximeter. Subjects were divided into two age groups: Group A (20-40 years) and
      Group B (> 40 years). One randomly selected eye of each subject was used for
      statistical analysis. Student's t tests were used to analyze the mean saturation
      and diameter of retinal arterioles and venules and arteriovenous differences
      between RP and normal subjects in the two age groups. A Spearman test was used to
      analyze the correlation of mean saturation of retinal arterioles (AS) and
      arteriovenous differences (AVS) with visual acuity, disease duration, and
      electroretinogram (ERG) b-wave amplitude in patients with RP. RESULTS: AS was
      significantly higher in patients with RP (105.5 +/- 9.4 %) than in normal
      subjects (94.5 +/- 4.4 %, p = 0.000) in Group A, while in Group B, AS was
      significantly lower in RP patients (86.8 +/- 10.3 %) than in healthy subjects
      (96.0 +/- 4.8 %, p = 0.000). Vessel diameter was smaller in RP patients than in
      normal subjects. AS and AVS showed a negative correlation with disease duration
      and a tendency toward positive correlation with ERG b-wave in patients with RP.
      CONCLUSIONS: The shifting characteristics of retinal vessel oxygen saturation
      suggest that the pathological mechanism of retinal oxygen metabolic disorder
      differs by age in patients with RP.

PMID- 25952045
TI  - Regional and seasonal variation in Clostridium difficile infections among
      hospitalized patients in the United States, 2001-2010.
AB  - BACKGROUND: This study identified national regional and seasonal variations in
      Clostridium difficile infection (CDI) incidence and mortality among hospitalized
      patients in the United States over a 10-year period. METHODS: This was a
      retrospective cohort study of the U.S. National Hospital Discharge Survey from
      2001-2010. Eligible cases had an ICD-9-CM discharge diagnosis code for CDI
      (008.45). Data weights were used to derive national estimates. CDI incidence and
      mortality were presented descriptively. Regions were as defined by the U.S.
      Census Bureau. Seasons included the following: winter (December-February), spring
      (March-May), summer (June-August), and fall (September-November). RESULTS: These
      data represent 2.3 million CDI discharges. Overall, CDI incidence was highest in
      the Northeast (8.0 CDIs/1,000 discharges) and spring (6.2 CDIs/1,000 discharges).
      CDI incidence was lowest in the West (4.8 CDIs/1,000 discharges) and fall (5.6
      CDIs/1,000 discharges). Peak CDI incidence among children occurred in the West
      (1.7 CDI/1,000 discharges) and winter (1.5 CDI/1,000 discharges). Mortality among
      all CDI patients was highest in the Midwest (7.3%) and during the winter (7.9%).
      CONCLUSION: The region and season with the highest CDI incidence rates among
      patients hospitalized in U.S. hospitals were the Northeast and spring,
      respectively. The highest CDI mortality rates were seen in the Midwest and
      winter. Children exhibited different regional and seasonal CDI variations
      compared with adults and older adults.

PMID- 25952043
TI  - Recalibration of blood analytes over 25 years in the atherosclerosis risk in
      communities study: impact of recalibration on chronic kidney disease prevalence
      and incidence.
AB  - BACKGROUND: Equivalence of laboratory tests over time is important for
      longitudinal studies. Even a small systematic difference (bias) can result in
      substantial misclassification. METHODS: We selected 200 Atherosclerosis Risk in
      Communities Study participants attending all 5 study visits over 25 years. Eight
      analytes were remeasured in 2011-2013 from stored blood samples from multiple
      visits: creatinine, uric acid, glucose, total cholesterol, HDL cholesterol, LDL
      cholesterol, triglycerides, and high-sensitivity C-reactive protein. Original
      values were recalibrated to remeasured values with Deming regression. Differences
      >10% were considered to reflect substantial bias, and correction equations were
      applied to affected analytes in the total study population. We examined trends in
      chronic kidney disease (CKD) pre- and postrecalibration. RESULTS: Repeat measures
      were highly correlated with original values [Pearson r > 0.85 after removing
      outliers (median 4.5% of paired measurements)], but 2 of 8 analytes (creatinine
      and uric acid) had differences >10%. Original values of creatinine and uric acid
      were recalibrated to current values with correction equations. CKD prevalence
      differed substantially after recalibration of creatinine (visits 1, 2, 4, and 5
      prerecalibration: 21.7%, 36.1%, 3.5%, and 29.4%, respectively; postrecalibration:
      1.3%, 2.2%, 6.4%, and 29.4%). For HDL cholesterol, the current direct enzymatic
      method differed substantially from magnesium dextran precipitation used during
      visits 1-4. CONCLUSIONS: Analytes remeasured in samples stored for approximately
      25 years were highly correlated with original values, but 2 of the 8 analytes
      showed substantial bias at multiple visits. Laboratory recalibration improved
      reproducibility of test results across visits and resulted in substantial
      differences in CKD prevalence. We demonstrate the importance of consistent
      recalibration of laboratory assays in a cohort study.

PMID- 25952046
TI  - Planning and response to Ebola virus disease: An integrated approach.
AB  - The care of patients with Ebola virus disease (EVD) requires the application of
      critical care medicine principles under conditions of stringent infection control
      precautions. The care of patients with EVD requires a number of elements in terms
      of physical layout, personal protective apparel, and other equipment. Provision
      of care is demanding in terms of depth of staff and training. The key to safely
      providing such care is a system that brings many valuable skills to the table,
      and allows communication between these individuals. We present our approach to
      leadership structure and function--a variation of incident command--in providing
      care to 3 patients with EVD.

PMID- 25952047
TI  - Ask, speak up, and be proactive: Empowering patient infection control to prevent
      health care-acquired infections.
AB  - BACKGROUND: Over the last decade, there has been a slow shift toward the more
      active engagement of patients and families in preventing health care-associated
      infections (HCAIs). This pilot study aimed to examine the receptiveness of
      hospital patients toward a new empowerment tool aimed at increasing awareness and
      engagement of patients in preventing HCAI. METHODS: Patients from the surgical
      department were recruited and randomized into 2 groups: active and control.
      Patients in the active arm were given an empowerment tool, whereas control
      patients continued with normal practices. Pre- and postsurveys were administered.
      RESULTS: At the baseline survey, just over half of the participants were highly
      willing to assist with infection control strategies. Participants were
      significantly more likely to be willing to ask a doctor or nurse a factual
      question then a challenging question. After discharge, 23 of the 60 patients
      reported discussing a health concern with a staff member; however, only 3
      participants asked a staff member to wash their hands. CONCLUSION: Our results
      suggest that patients would like to be more informed about HCAIs and are willing
      to engage with staff members to assist with the prevention of infections while in
      the hospital setting. Further work is going to need to be undertaken to ascertain
      the best strategies to promote engagement and participation in infection control
      activities.

PMID- 25952048
TI  - Central line-associated blood stream infections in pediatric intensive care
      units: Longitudinal trends and compliance with bundle strategies.
AB  - BACKGROUND: Knowing the temporal trend central line-associated bloodstream
      infection (CLABSI) rates among U.S. pediatric intensive care units (PICUs), the
      current extent of central line bundle compliance, and the impact of compliance on
      rates is necessary to understand what has been accomplished and can be improved
      in CLABSI prevention. METHODS: This is a longitudinal study of PICUs in National
      Healthcare Safety Network hospitals and a cross-sectional survey of directors and
      managers of infection prevention and control departments regarding PICU CLABSI
      prevention practices, including self-reported compliance with elements of central
      line bundles. Associations between 2011-2012 PICU CLABSI rates and infection
      prevention practices were examined. RESULTS: Reported CLABSI rates decreased
      during the study period, from 5.8 per 1,000 line days in 2006 to 1.4 in 2011-2012
      (P < .001). Although 73% of PICUs had policies for all central line prevention
      practices, only 35% of those with policies reported >=95% compliance. PICUs with
      >=95% compliance with central line infection prevention policies had lower
      reported CLABSI rates, but this association was statistically insignificant.
      CONCLUSION: There was a nonsignificant trend in decreasing CLABSI rates as PICUs
      improved bundle policy compliance. Given that few PICUs reported full compliance
      with these policies, PICUs increasing their efforts to comply with these policies
      may help reduce CLABSI rates.

PMID- 25952049
TI  - Analysis of microbial load on surgical instruments after clinical use and
      following manual and automated cleaning.
AB  - BACKGROUND: We aimed to monitor the microbial load and identify the
      microorganisms recovered from surgical instruments after clinical use and
      following manual and automated cleaning. METHODS: This experimental study was
      carried out in the Laboratory of Oral Microbiology and Anaerobes at the Federal
      University of Minas Gerais in Brazil. Microbial samples were taken from 125
      surgical instruments used in 25 types of gastrointestinal surgeries. RESULTS: The
      average microbial load was 93.1 CFU/100 mL after clinical use and 41 CFU/100 mL
      and 8.24 CFU/100 mL on instruments following 2 sequential steps of manual
      cleaning, respectively, and 75 CFU/100 mL and 16.1 CFU/100 mL on instruments
      after automated cleaning. Surgical wound classification significantly affected
      the microbial load recovered on instruments. Coagulase-negative Staphylococcus,
      Escherichia coli, Pseudomonas spp, Stenotrophomonas maltophilia, and
      Acinetobacter baumannii complex were recovered. CONCLUSIONS: The average
      microbial load observed after the cleaning steps decreased, and the decrease in
      microbial load was more pronounced using the manual method compared with that
      observed using the automated method.

PMID- 25952050
TI  - Novel handwashes are superior to soap and water in removal of Clostridium
      difficile spores from the hands.
AB  - We examined the efficacy of 5 experimental handwash formulations in removing
      nontoxigenic Clostridium difficile spores from the hands of health care workers.
      Handwashing with sand resulted in an additional 0.5-log reduction in spore
      recovery compared with the current standard of soap and water. 

PMID- 25952051
TI  - Relationship between knowledge and attitudes of methicillin-resistant
      Staphylococcus aureus and hand hygiene behavior in Veterans with spinal cord
      injury and disorder.
AB  - The objective of this analysis was to understand the relationship between
      knowledge and attitudes regarding methicillin-resistant Staphylococcus aureus and
      hand hygiene behavior based on a baseline survey administered to Veterans with
      spinal cord injuries and disorders. Higher knowledge was associated with higher
      attitude scores (r = 0.35, P = .003), but knowledge and attitudes were not
      associated with behavior. Also, those with quadriplegia had higher knowledge
      scores (P = .03). Knowledge and attitudes, although related, do not appear to
      fully explain patients' hand hygiene behavior. 

PMID- 25952052
TI  - Efficient construction of stable gene nanoparticles through polymerase chain
      reaction with flexible branched primers for gene delivery.
AB  - Flexible branched primers were designed to construct stable gene nanoparticles
      with multiple target gene copies through polymerase chain reaction, which can be
      used as an efficient transcription template in eukaryotic cells for gene
      delivery. 

PMID- 25952053
TI  - Electronic health records to support obesity-related patient care: Results from a
      survey of United States physicians.
AB  - OBJECTIVE: Obesity-related electronic health record functions increase the rates
      of measuring Body Mass Index, diagnosing obesity, and providing obesity services.
      This study describes the prevalence of obesity-related electronic health record
      functions in clinical practice and analyzes characteristics associated with
      increased obesity-related electronic health record sophistication. METHODS: Data
      were analyzed from DocStyles, a web-based panel survey administered to 1507
      primary care providers practicing in the United States in June, 2013. Physicians
      were asked if their electronic health record has specific obesity-related
      functions. Logistical regression analyses identified characteristics associated
      with improved obesity-related electronic health record sophistication. RESULTS:
      Of the 88% of providers with an electronic health record, 83% of electronic
      health records calculate Body Mass Index, 52% calculate pediatric Body Mass Index
      percentile, and 32% flag patients with abnormal Body Mass Index values. Only 36%
      provide obesity-related decision support and 17% suggest additional resources for
      obesity-related care. Characteristics associated with having a more sophisticated
      electronic health record include age <=45years old, being a pediatrician or
      family practitioner, and practicing in a larger, outpatient practice.
      CONCLUSIONS: Few electronic health records optimally supported physician's
      obesity-related clinical care. The low rates of obesity-related electronic health
      record functions currently in practice highlight areas to improve the clinical
      health information technology in primary care practice. More work can be done to
      develop, implement, and promote the effective utilization of obesity-related
      electronic health record functions to improve obesity treatment and prevention
      efforts.

PMID- 25952054
TI  - Assessing views about gun violence reduction policy: a look at type of violence
      and expected effectiveness.
AB  - OBJECTIVE: Public opinion polling about gun policy is routinely conducted and
      often disregarded. The purpose of this research is to explore ways in which
      surveys can be made more useful to policy makers, researchers, and the general
      public. METHODS: A stratified random sample of 1000 undergraduates at a private,
      urban university was recruited for an online survey about proposed gun policies.
      A total of 51.7% answered the questions analyzed herein. Including but going
      beyond typical assessments of agreement, the survey elicited respondent
      evaluations of the effectiveness of seven gun policies under two randomly
      assigned conditions: the type of gun violence (e.g., homicide, suicide, violent
      crime) and its magnitude. Participants were asked to estimate the effectiveness
      of each policy, including the possibility of making things worse. RESULTS:
      Participants indicated strong support for all policies and expected each to be
      effective with one exception - a policy designed to increase the number of guns
      on the scene, that is, putting armed police in schools. Persons who did not
      support other policies, on average, did not expect them to make things worse.
      Telling participants about the scope of the violence did not but the type of gun
      violence did affect effectiveness ratings. CONCLUSIONS: Asking about expected
      effectiveness of (vs. general support for) a policy might identify some optimism:
      Even people who don't support a policy sometimes think it will be effective.
      Findings suggest that surveys about the effectiveness of gun violence policies
      likely assess views that exclude suicide, the most common form of gun-related
      mortality.

PMID- 25952055
TI  - A randomised controlled trial on the effectiveness of a home-based self
      management programme for community-dwelling patients with myocardial infarction.
AB  - AIM: To examine the effectiveness of a four-week home-based self-management
      rehabilitation programme on health-related quality of life, anxiety and
      depression levels, cardiac risks and unplanned visits to the health services
      among community-dwelling patients with myocardial infarction. METHODS: A
      randomised controlled trial with repeated measurements was used. A convenience
      sample of 128 patients with myocardial infarction was recruited from outpatient
      cardiology clinics at a tertiary hospital in Singapore. Participants were
      randomly assigned to the intervention group or control group. The outcomes were
      measured using Short Form 12-item Health Survey Version 2, Myocardial Infarction
      Dimensional Assessment Scale, and Hospital Anxiety and Depression Scale. The
      cardiac physiological risk parameters and number of unplanned health service use
      were also assessed. Data were collected at baseline, and at four weeks and 16
      weeks from the baseline. RESULTS: Over the 16 weeks, the two groups reported
      significant differences in physical activity (F = 4.23, p = 0.02), dependency (F
      = 5.16, p = 0.01), concerns over medication (F = 3.47, p = 0.04) on MIDAS,
      anxiety level (F = 3.41, p = 0.04) and body mass index (F = 3.12, p = 0.04). A
      significant difference was also found in unplanned cardiac-related emergency room
      visits (chi(2) = 6.64, p = 0.036) and medical consultation (chi(2) = 9.67, p =
      0.046) at the 16-week study point. CONCLUSION: The study may provide a useful
      tool to help health care professionals to meet the cardiac rehabilitative care
      needs of community-dwelling patients with myocardial infarction in Singapore.

PMID- 25952056
TI  - Is sexual health an issue in nursing education?

PMID- 25952058
TI  - Executive dysfunction affects word list recall performance: Evidence from
      amyotrophic lateral sclerosis and other neurodegenerative diseases.
AB  - The Rey Auditory Verbal Learning Test (RAVLT) is widely used in clinical practice
      to evaluate verbal episodic memory. While there is evidence that RAVLT
      performance can be influenced by executive dysfunction, the way executive
      disorders affect the serial position curve (SPC) has not been yet explored. To
      this aim, we analysed immediate and delayed recall performances of 13 non
      demented amyotrophic lateral sclerosis (ALS) patients with a specific mild
      executive dysfunction (ALSci) and compared their performances to those of 48
      healthy controls (HC) and 13 cognitively normal patients with ALS. Moreover, to
      control for the impact of a severe dysexecutive syndrome and a genuine episodic
      memory deficit on the SPC, we enrolled 15 patients with a diagnosis of
      behavioural variant of frontotemporal dementia (bvFTD) and 18 patients with
      probable Alzheimer's disease (AD). Results documented that, compared to
      cognitively normal subjects, ALSci patients had a selective mid-list impairment
      for immediate recall scores. The bvFTD group obtained low performances with a
      selectively increased forgetting rate for terminal items, whereas the AD group
      showed a disproportionately large memory loss on the primary and middle part of
      the SPC for immediate recall scores and were severely impaired in the delayed
      recall trial. These results suggested that subtle executive dysfunctions might
      influence the recall of mid-list items, possibly reflecting deficiency in control
      strategies at retrieval of word lists, whereas severer dysexecutive syndrome
      might also affect the recall of terminal items possibly due to attention deficit
      or retroactive interference.

PMID- 25952057
TI  - In vitro studies in a myelogenous leukemia cell line suggest an organized binding
      of geranylgeranyl diphosphate synthase inhibitors.
AB  - A small set of isoprenoid bisphosphonates ethers has been tested in the K562
      chronic myelogenous leukemia cell line to determine their impact on isoprenoid
      biosynthesis. Five of these compounds inhibit geranylgeranyl diphosphate synthase
      (GGDPS) with IC50 values below 1 MUM in enzyme assays, but in cells their
      apparent activity is more varied. In particular, the isomeric C-geranyl-O-prenyl
      and C-prenyl-O-geranyl bisphosphonates are quite different in their activity with
      the former consistently demonstrating greater impairment of geranylgeranylation
      in cells but the latter showing greater impact in the enzyme assays with GGDPS.
      Together, these findings suggest an organized binding of these inhibitors in the
      two hydrophobic channels of the geranylgeranyl diphosphate synthase enzyme.

PMID- 25952059
TI  - Central hypersensitivity in chronic musculoskeletal pain.
AB  - Clinical research has consistently detected alteration in central pain processing
      leading to hypersensitivity. Most methods used in humans are reliable and have
      face validity to detect widespread central hypersensitivity. However, construct
      validity is difficult to investigate due to lack of gold standards. Reference
      values in the pain-free population have been generated, but need replication.
      Research on pain biomarkers that reflect specific central hypersensitivity
      processes is warranted. Few studies have analyzed the prognostic value of central
      hypersensitivity. Most medications acting at central level and some non
      pharmacological approaches, including psychological interventions, are likely to
      attenuate central hypersensitivity. 

PMID- 25952060
TI  - Chronic pain assessment.
AB  - To be accurate with chronic pain assessment, the medical examiner should be alert
      to specific diagnoses in addition to global markers of decreased function
      associated with chronic pain, such as disability and depression. The key to
      accurate assessment is to avoid making assumptions before doing a complete
      history and physical examination. This article focuses on the history and
      examination and emphasizes pitfalls associated with overreliance on medical
      technology. 

PMID- 25952061
TI  - Opioid therapy in chronic pain.
AB  - Opioids remain the strongest and most effective analgesics available. The
      downside is that they are addictive and potentially dangerous. Throughout
      history, although recognizing the value of opioids in treating serious pain,
      especially acute pain and pain at the end of life, there has been caution about
      using opioids to treat chronic pain. This article presents how opioids should be
      used to treat chronic pain considering recent concerns about their efficacy and
      safety. 

PMID- 25952062
TI  - Nonopioid medications for pain.
AB  - Evidence of nonopioid analgesic effectiveness exceeds that for long-term opioids
      in chronic noncancer pain (CNCP), most with lower risk. Non-drug therapies such
      as cognitive behavioral therapy and physical activation are safer and also
      effective. Nonsteroidal antiinflammatory drugs are useful for inflammatory and
      nociceptive pain, share renal and variable gastrointestinal, bleeding and
      cardiovascular side effects. Antidepressants with noradrenergic activity (such as
      tricyclics and seroton-norepinephrine reuptake inhibitors) and neuromodulating
      anticonvulsant drugs (gabapentinoids and sodium-channel blockers) are proven to
      be effective for neuropathic and centralized pain. Ketamine and cannabinoids are
      other studied analgesics but have a less well-proven role in CNCP. 

PMID- 25952063
TI  - Injections for chronic pain.
AB  - Although interventional procedures should be used cautiously in the setting of
      chronic pain, there is a role for a variety of injections to facilitate a
      patient's overall rehabilitation program. There are many resources available,
      including a prior issue of Physical Medicine and Rehabilitation Clinics of North
      America, which discuss the more conventional spinal injections. The focus of this
      article is on lesser-known injection options for treating chronic pain. The
      authors separately discuss trigger point injections, regenerative injections
      (prolotherapy), and injections using botulin toxins. 

PMID- 25952064
TI  - Exercise therapy for chronic pain.
AB  - The benefit of exercise for pain control likely comes from the impact of exercise
      on the endogenous opioid system and on central pain modulatory systems. Patients
      with some chronic pain conditions seem to have a dysfunctional endogenous pain
      modulatory system, which should be considered when prescribing exercise. The
      prescription of exercise for chronic pain must address the biomechanical issues
      and the psychosocial factors that contribute to the patient's pain and
      disability. Patient education, coordination of care within the health care team,
      and selecting an exercise regimen that is meaningful to and achievable by the
      patient are all important components to promote a successful rehabilitation
      program. 

PMID- 25952065
TI  - Psychiatric and psychological perspectives on chronic pain.
AB  - Chronic pain patients often have psychiatric disorders that negatively influence
      their responses to treatment. Also, many of them have dysfunctional beliefs and
      coping strategies, even if they do not meet DSM-5 criteria for a psychiatric
      disorder. Physiatrists should have a low threshold for referring both groups of
      patients for mental health services. This article describes psychiatric disorders
      that are highly prevalent among pain patients and also describes psychological
      processes that contribute to poor coping by the patients. Finally, it discusses
      factors that a physiatrist should consider in deciding whether to refer patients
      to psychiatrists versus psychologists. 

PMID- 25952066
TI  - Sleep: important considerations in management of pain.
AB  - Sleep patterns share common pathways with nociceptive stimuli. Several important
      factors are reviewed in considering connections between sleep and pain. Causes
      for sleep fragmentation include sleep disordered breathing; abnormal leg
      movements, including restless legs syndrome and periodic limb movements; and
      underlying mood disorder, which may be exacerbated by physical symptoms.
      Identification and management of insomnia includes the definition of the
      condition, pharmacologic interventions, the role of circadian rhythms and clock
      adjustments, and the use of cognitive behavior therapy for insomnia. 

PMID- 25952067
TI  - Nutrition and pain.
AB  - Research is providing compelling evidence for Hippocrates' oft quoted "Let food
      be thy medicine." Despite this, most graduating physicians receive only a few
      hours of instruction about nutrition and coaching to help patients change their
      eating habits. Appropriate nutritional interventions may be one of the most
      useful tools doctors have to improve overall health outcomes in their patients
      and specifically reduce inflammation. Whether doctors choose to do this
      themselves or collaborate with other professionals trained in nutritional
      coaching, the benefits of attending to nutritional status can enhance outcomes of
      other therapies. 

PMID- 25952068
TI  - Complementary medicine in chronic pain treatment.
AB  - This article discusses several issues related to therapies that are considered
      "complementary" or "alternative" to conventional medicine. A definition of
      "complementary and alternative medicine" (CAM) is considered in the context of
      the evolving health care field of complementary medicine. A rationale for pain
      physicians and clinicians to understand these treatments of chronic pain is
      presented. The challenges of an evidence-based approach to incorporating CAM
      therapies are explored. Finally, a brief survey of the evidence that supports
      several widely available and commonly used complementary therapies for chronic
      pain is provided. 

PMID- 25952069
TI  - Interdisciplinary rehabilitation.
AB  - Interdisciplinary pain rehabilitation programs are infrequently used in the
      United States in the treatment of chronic pain. Comprehensively addressing the
      contributors to chronic pain, which include behavioral, psychological, and
      physical dimensions, has shown evidence-based efficacy in improving functioning
      and reducing pain-related distress. This approach also holds the potential for
      reducing the escalating costs of chronic pain care. 

PMID- 25952070
TI  - Chronic whiplash pain.
AB  - Although most patients recover from acute whiplash injuries, those with chronic
      whiplash syndrome develop signs of central nervous system (CNS) amplification of
      pain and have a poor prognosis. In this context, specific pain generators from
      acute whiplash have been identified through clinical, biomechanical, and animal
      studies. This article gives a clinical perspective on current understanding of
      these pain generators, including the phenomenon of CNS sensitization. 

PMID- 25952071
TI  - Chronic daily headache.
AB  - Chronic daily headache (CDH) is a challenging condition to treat. CDH is often
      accompanied by significant comorbidities, such as chronic fatigue, depression,
      anxiety, and insomnia, which further complicate treatment. Unrealistic
      expectations of treatment goals can lead to patient frustration, and, as a
      result, decrease treatment adherence. Patients often desire headache-free status,
      but this outcome is not realistic for many patients with CDH. By contrast, an
      effective treatment goal starts with establishing the correct diagnosis and
      creating a multimodal treatment plan to improve function and well-being. With
      proper comprehensive treatment, the condition improves in most patients. 

PMID- 25952072
TI  - Pain and the injured worker.
AB  - Physicians who treat injured workers with painful conditions face complex
      challenges that require skills beyond those of a clinician. To address these
      challenges effectively, physicians need to understand the logic of workers'
      compensation systems and the interests of the various participants in the
      systems. They must be prepared to interface constructively between their patients
      and the workers' compensation carrier and attend to a multitude of administrative
      issues. In the present article, the authors provide an extended case history with
      commentary to illustrate the challenges that physicians face and the ways they
      can respond to these challenges. 

PMID- 25952074
TI  - Chronic pain.

PMID- 25952075
TI  - Maturation of human iPS cell-derived dopamine neuron precursors in alginate
      Ca(2+) hydrogel.
AB  - BACKGROUND: Pluripotent stem cells (embryonic stem/induced pluripotent stem
      cells) have been widely studied as a potential cell source for cell
      transplantation therapy of Parkinson's disease. However, some difficulties remain
      to be overcome. These include the need to prepare a large number of dopamine (DA)
      neurons for clinical use and to culture the cells for a long period to allow
      their functional maturation and the removal of undifferentiated cells. METHODS:
      In this study, aggregates of DA neuron precursors were enclosed in alginate
      Ca(2+) microbeads, and the encapsulated aggregates were cultured for 25days to
      induce cell maturation. RESULTS: More than 60% of cells in the aggregates
      differentiated into tyrosine hydroxylase-positive DA neurons. The aggregates
      could release DA at the same level as aggregates maintained on culture dishes
      without encapsulation. In addition, by exposure to a citrate solution, the
      alginate-Ca(2+) gel layer could be easily removed from aggregates without
      damaging the DA neurons. When the aggregates were transplanted into rat brain,
      viable cells were found in the graft at one week post-transplantation, with cells
      extending neurites into the host tissue. CONCLUSIONS: Cell aggregates
      encapsulated in alginate-Ca(2+) beads successfully differentiated into mature DA
      neurons. GENERAL SIGNIFICANCE: The alginate-Ca(2+) microbead is suitable for
      maintaining DA precursor aggregates for a long period to allow their functional
      maturation.

PMID- 25952076
TI  - Polyp-Alert: near real-time feedback during colonoscopy.
AB  - We present a software system called "Polyp-Alert" to assist the endoscopist find
      polyps by providing visual feedback during colonoscopy. Polyp-Alert employs our
      previous edge-cross-section visual features and a rule-based classifier to detect
      a polyp edge-an edge along the contour of a polyp. The technique employs tracking
      of detected polyp edge(s) to group a sequence of images covering the same
      polyp(s) as one polyp shot. In our experiments, the software correctly detected
      97.7% (42 of 43) of polyp shots on 53 randomly selected video files of entire
      colonoscopy procedures. However, Polyp-Alert incorrectly marked only 4.3% of a
      full-length colonoscopy procedure as showing a polyp when they do not. The test
      data set consists of about 18 h worth of video data from Olympus and Fujinon
      endoscopes. The technique is extensible to other brands of colonoscopes.
      Furthermore, Polyp-Alert can provide as high as ten feedbacks per second for a
      smooth display of feedback. The performance of our system is by far the most
      promising to potentially assist the endoscopist find more polyps in clinical
      practice during a routine screening colonoscopy.

PMID- 25952077
TI  - Wettability influence on the onset temperature of pool boiling: Experimental
      evidence onto ultra-smooth surfaces.
AB  - In this article we study systematically the effect of wettability on the onset of
      boiling on the same nanometrically smooth surface. By grafting different
      monolayers of molecules, we were able to explore the wettability from the
      equilibrium static contact angle, theta0=0 degrees  to theta0=110 degrees ,
      without changing the surface topography. The superheat temperature at the onset
      of pool boiling was measured and eventually a non-classical trend of TONB as a
      function of wettability was observed. The nucleation site densities for the
      different grafting cases were also measured by image analysis. Moreover, we
      propose a novel theoretical interpretation to this phenomenon linking nucleation
      and the molecular diffusion coefficient. MD simulation results support this
      approach. 

PMID- 25952078
TI  - Treatment of clinical endometritis in dairy cows by previously used controlled
      internal drug release devices.
AB  - Postpartum endometritis is considered as one of the diseases that lead to a
      potential profit reduction in dairy cows. The aims of the present study were to
      promote follicle growth by a previously used controlled internal drug release
      (CIDR) device and to evaluate its effect on the likelihood of recovery and the
      reproductive performance of clinical endometritis (CE) cows. Endometritis was
      diagnosed using ultrasonographic examination at 31 +/- 3 (Day 0 of the
      experiment) days in milk, and CE cows were included in one of the three
      experimental groups according to the presence of a CL on their ovaries. Cows
      without CL on their ovaries received a reused CIDR device, which was previously
      used for 14 days (CIDR-14, n = 108), or PGF2alpha (PG-1, n = 112) on Day 0. In
      the third group, those with CL on their ovaries received PGF2alpha (PG-2, n =
      107) at the same time. Ovarian structures, serum estradiol and progesterone
      concentrations were measured on Days 0, 7, and 14. Controlled internal drug
      release devices were removed, and response to treatment was evaluated in all
      treated cows on Day 14. Diameters of ovarian follicles were 11.61 +/- 0.50, 12.46
      +/- 0.25, and 18.36 +/- 0.60 mm on Day 7 and 11.63 +/- 0.58, 14.35 +/- 0.40, and
      21.96 +/- 0.77 mm on Day 14 in PG-1, PG-2, and CIDR-14 cows, respectively (P <
      0.05). Serum estradiol concentrations were higher in CIDR-14 cows (141.17 +/-
      1.04 pg/mL) than in PG-1 (116.85 +/- 1.05 pg/mL) and PG-2 (119.10 +/- 1.05 pg/mL)
      cows on Day 7 (P < 0.05). Higher progesterone concentrations were observed in PG
      2 cows than in PG-1 and CIDR-14 cows on Days 0, 7, and 14 (P < 0.001). The
      likelihood of clinical cure was 54.46%, 62.61%, and 64.81% in PG-1, PG-2, and
      CIDR-14 cows, respectively (P = 0.11). First-service conception risk, days to the
      first service, calving to conception interval, proportion of cows bred and
      pregnant by 120 days in milk did not differ among the treated groups (P > 0.05).
      The cumulative pregnancy risk was lower in PG-1 (77.67%) cows than in CIDR-14
      (87.07%) and PG-2 (87.85%) cows (P = 0.02). In conclusion, reused CIDR would be
      contributed to the treatment of CE by promotion of follicle growth and induction
      of sustainable sources of endogenic estrogen secreted by the dominant follicle.

PMID- 25952079
TI  - Left atrio-esophageal fistula of a possibly iatrogenic aetiology.
AB  - The study presents an exceptionally rare case of an esophago-left atrial fistula,
      which was diagnosed during a forensic post-mortem examination. Due to complex
      nature of the disease and many attempts to cure the patient, the authors did not
      manage to identify the aetiology of the fistula. It was only implied that the
      fistula might have been a distant complication of intraoperative endocardial
      ablation or it might have appeared as a consequence of perforation of the
      esophageal wall or left atrial wall of the enlarged heart with the end of an
      intubation tube or nasogastric tube. 

PMID- 25952080
TI  - Rapid Reticulin Fiber Staining Method is Helpful for the Diagnosis of Pituitary
      Adenoma in Frozen Section.
AB  - Approximately 90% of neoplasms found in the sellar region are adenoma of the
      pituitary gland. The use of frozen sections for the diagnosis of pituitary
      adenomas has an accuracy of 90% and is useful in evaluating complete tumor
      removal. However, it is sometimes difficult to diagnose pituitary adenomas using
      frozen sections because of the small sample size and marked artifact, and the
      contiguity of the pituitary adenoma with normal pituitary gland tissue. In this
      study, we evaluated the use of our modified reticulin stain to make correct
      decision in frozen section with reduced stain time and investigated the objective
      diagnostic criteria of pituitary adenoma with reticulin stain. We used Gomori's
      silver impregnation methods to stain reticulin fibers in frozen pituitary gland
      sections of 36 samples from 24 patients. We modified the conventional staining
      method by reducing the overall staining time. We diagnosed pituitary lesion
      according to our interpretation criteria and compared the results to those of the
      conventional method and findings of hematoxylin and eosin-stained slides.
      Reticulin fiber staining of normal adenohypophysis outlines the supporting stroma
      around the blood vessels and shows regular of the gland meshwork interconnecting
      the capillaries. In contrast, reticulin fiber staining of the adenomatous tissue
      shows loss of meshwork or frequent fragmentation. Our modified reticulin stain is
      more rapid than the established method and shows similar levels of accuracy.
      Independent evaluation by two pathologists showed discrepancies in diagnosis in
      four out of 36 cases with modified reticulin stain. Our rapid modified reticulin
      staining method for frozen sections may be useful as a diagnostic tool for
      pituitary adenomas and can complement routine hematoxylin and eosin staining.

PMID- 25952081
TI  - Magnetic fields: how is plant growth and development impacted?
AB  - This review provides detailed insight on the effects of magnetic fields on
      germination, growth, development, and yield of plants focusing on ex vitro growth
      and development and discussing the possible physiological and biochemical
      responses. The MFs considered in this review range from the nanoTesla (nT) to
      geomagnetic levels, up to very strong MFs greater than 15 Tesla (T) and also
      super-weak MFs (near 0 T). The theoretical bases of the action of MFs on plant
      growth, which are complex, are not discussed here and thus far, there is limited
      mathematical background about the action of MFs on plant growth. MFs can
      positively influence the morphogenesis of several plants which allows them to be
      used in practical situations. MFs have thus far been shown to modify seed
      germination and affect seedling growth and development in a wide range of plants,
      including field, fodder, and industrial crops; cereals and pseudo-cereals;
      grasses; herbs and medicinal plants; horticultural crops (vegetables, fruits,
      ornamentals); trees; and model crops. This is important since MFs may constitute
      a non-residual and non-toxic stimulus. In addition to presenting and summarizing
      the effects of MFs on plant growth and development, we also provide possible
      physiological and biochemical explanations for these responses including stress
      related responses of plants, explanations based on dia-, para-, and
      ferromagnetism, oriented movements of substances, and cellular and molecular
      changes.

PMID- 25952082
TI  - Functional characterization of secondary wall deposition regulating transcription
      factors MusaVND2 and MusaVND3 in transgenic banana plants.
AB  - NAM, ATAF, and CUC (NAC) domain-containing proteins are plant-specific
      transcription factors involved in stress responses and developmental regulation.
      MusaVND2 and MusaVND3 are vascular-related NAC domain-containing genes encoding
      for nuclear-localized proteins. The transcript level of MusaVND2 and MusaVND3 are
      gradually induced after induction of lignification conditions in banana
      embryogenic cells. Banana embryogenic cells differentiated to tracheary element
      like cells after overexpression of MusaVND2 and MusaVND3 with a differentiation
      frequency of 63.5 and 23.4 %, respectively, after ninth day. Transgenic banana
      plants overexpressing either of MusaVND2 or MusaVND3 showed ectopic secondary
      wall deposition as well as transdifferentiation of cells into tracheary elements.
      Transdifferentiation to tracheary element-like cells was observed in cortical
      cells of corm and in epidermal and mesophyll cells of leaves of transgenic
      plants. Elevated levels of lignin and crystalline cellulose were detected in the
      transgenic banana lines than control plants. The results obtained are useful for
      understanding the molecular regulation of secondary wall development in banana.

PMID- 25952084
TI  - Environmental factors and dam characteristics associated with insulin sensitivity
      and insulin secretion in newborn Holstein calves.
AB  - The objective of the present retrospective cohort study was to evaluate potential
      associations between environmental factors and dam characteristics, including
      level of milk production during gestation, and insulin traits in newborn Holstein
      calves. Birth weight and gestational age of the calves at delivery were
      determined. On the next day, heart girth, wither height and diagonal length of
      both the calves and their dams were measured. Parity, body condition score and
      age at calving were recorded for all dams. For the cows, days open before last
      gestation, lactation length (LL), length of dry period (DP) and calving interval
      were also calculated. The magnitude and shape of the lactation curve both
      quantified using the MilkBot model based on monthly milk weights, were used to
      calculate the amount of milk produced during gestation. Using the same procedure,
      cumulative milk production from conception to drying off (MGEST) was calculated.
      A blood sample was collected from all calves (n=481; 169 born to heifers and 312
      born to cows) at least 5 h after a milk meal on day 3 of life to measure basal
      glucose and insulin levels. In addition, an intravenous glucose-stimulated
      insulin secretion test was performed in a subset of the calves (n=316). After
      descriptive analysis, generalized linear mixed models were used to identify
      factors that were significantly associated with the major insulin traits (Insb,
      basal insulin level; QUICKI, quantitative insulin sensitivity check index; AIR,
      acute insulin response; DI, disposition index) of the newborn calves. The overall
      average birth weight of the calves was 42.7 +/- 5.92 kg. The insulin traits were
      significantly associated with gender and season of birth when data of all calves
      were analyzed. In addition, the insulin traits in calves born to cows were
      significantly associated with MGEST, DP and LL. The Insb was estimated to be
      higher in calves born to the cows having passed a higher MGEST (P=0.076) and
      longer DP (P=0.034). The QUICKI was estimated to be lower in calves born to the
      cows having passed a higher MGEST (P=0.030) and longer DP (P=0.058). Moreover,
      the AIR (P=0.009) and DI (P=0.049) were estimated to be lower in male compared
      with female calves. Furthermore, the AIR (P=0.036) and DI (P=0.039) were
      estimated to be lower in calves born to cows having passed a longer LL. The
      decisive effects of MGEST, DP and LL in cows on the insulin traits of their
      calves may provide a basis for developing managerial interventions to improve
      metabolic health of the offspring.

PMID- 25952083
TI  - Oxidative and antioxidative responses in the wheat-Azospirillum brasilense
      interaction.
AB  - Azospirillum is a plant growth-promoting rhizobacteria (PGPR) able to enhance the
      growth of wheat. The aim of this study was to test the effect of Azospirillum
      brasilense cell wall components on superoxide (O2.(-)) production in wheat roots
      and the effect of oxidative stress on A. brasilense viability. We found that
      inoculation with A. brasilense reduced O2.(-) levels by approx. 30 % in wheat
      roots. Inoculation of wheat with papain-treated A. brasilense, a Cys protease,
      notably increased O2.(-) production in all root tissues, as was observed by the
      nitro blue tetrazolium (NBT) reduction. However, a 24-h treatment with
      rhizobacteria lipopolysaccharides (50 and 100 MUg/mL) alone did not affect the
      pattern of O2.(-) production. Analysis of the effect of plant cell wall
      components on A. brasilense oxidative enzyme activity showed no changes in
      catalase activity but a decrease in superoxide dismutase activity in response to
      polygalacturonic acid treatment. Furthermore, A. brasilense growth was only
      affected by high concentrations of H2O2 or paraquat, but not by sodium
      nitroprusside. Our results suggest that rhizobacterial cell wall components play
      an important role in controlling plant cell responses and developing tolerance of
      A. brasilense to oxidative stress produced by the plant.

PMID- 25952085
TI  - Narrow-band imaging versus white light for the detection of proximal colon
      serrated lesions: a randomized, controlled trial.
AB  - BACKGROUND: The value of narrow-band imaging (NBI) for detecting serrated lesions
      is unknown. OBJECTIVE: To assess NBI for the detection of proximal colon serrated
      lesions. DESIGN: Randomized, controlled trial. SETTING: Two academic hospital
      outpatient units. PATIENTS: Eight hundred outpatients 50 years of age and older
      with intact colons undergoing routine screening, surveillance, or diagnostic
      examinations. INTERVENTIONS: Randomization to colon inspection in NBI versus
      white-light colonoscopy. MAIN OUTCOME MEASUREMENTS: The number of serrated
      lesions (sessile serrated polyps plus hyperplastic polyps) proximal to the
      sigmoid colon. RESULTS: The mean inspection times for the whole colon and
      proximal colon were the same for the NBI and white-light groups. There were 204
      proximal colon lesions in the NBI group and 158 in the white light group (P =
      .085). Detection of conventional adenomas was comparable in the 2 groups.
      LIMITATIONS: Lack of blinding, endoscopic estimation of polyp location.
      CONCLUSION: NBI may increase the detection of proximal colon serrated lesions,
      but the result in this trial did not reach significance. Additional study of this
      issue is warranted. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01572428.).

PMID- 25952086
TI  - EUS-directed transgastric ERCP for Roux-en-Y gastric bypass anatomy: a minimally
      invasive approach.
AB  - BACKGROUND: ERCP is challenging in patients with Roux-en-Y gastric bypass. Using
      EUS to gain access to the excluded stomach and subsequently performing
      transcutaneous ERCP was described recently. OBJECTIVE: We describe our initial
      experience with an internal EUS-directed transgastric ERCP (EDGE) procedure by
      using a lumen-apposing metal stent (LAMS). DESIGN: Single-center case series.
      SETTING: Tertiary center with expertise in EUS-guided procedures. PATIENTS: Five
      patients with Roux-en-Y gastric bypass underwent EDGE via a LAMS. INTERVENTIONS:
      A linear echoendoscope was used to access the excluded stomach. A LAMS was
      deployed over a wire to create a gastrogastric or jejunogastric fistula. A
      duodenoscope was then passed through the LAMS and conventional ERCP was
      performed. MAIN OUTCOME MEASUREMENTS: Technical and clinical success rates as
      well as adverse events. RESULTS: EUS-guided creation of a gastrogastric or
      jejunogastric fistula via placement of a LAMS was successful in all cases (100%).
      The ability to perform ERCP through the fashioned fistula during the index
      procedure was successful in 3 of 5 cases (60%). Two LAMS dislodgments requiring
      restenting were observed. No major adverse events were observed. No weight regain
      occurred. The median procedure time was 68.0 minutes. LIMITATIONS: Small sample,
      single-institution experience. CONCLUSION: The internal EDGE procedure may offer
      a cost-effective, minimally invasive option for a common problem in a growing
      patient demographic. Further refinement of the technique is required to minimize
      adverse events. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01522573.).

PMID- 25952087
TI  - Therapeutic outcomes of endoscopic submucosal dissection of differentiated early
      gastric cancer in a Western endoscopy setting (with video).
AB  - BACKGROUND: Large multicenter gastric cancer endoscopic submucosal dissection
      (ESD) studies conducted at major Japanese institutions have reported en bloc
      resection, en bloc tumor-free margin resection, and curative resection rates of
      92.7% to 96.1%, 82.6% to 94.5%, and 73.6% to 85.4%, respectively, with delayed
      bleeding and perforation rates of 0.6% to 6.0% and 3.6% to 4.7%, respectively.
      Although ESD is currently an alternative treatment in some countries,
      particularly in Asia, it remains uncertain whether ESD therapeutic outcomes in
      Western endoscopy settings can be comparable to those achieved in Japan.
      OBJECTIVE: To evaluate the ESD therapeutic outcomes for differentiated early
      gastric cancer (EGC) in a Western endoscopy setting. DESIGN/SETTING: Consecutive
      case series performed by an expertly trained Western endoscopist. PATIENTS: Fifty
      three patients with 54 lesions. INTERVENTIONS: ESD for early gastric cancers (T1)
      satisfying expanded inclusion criteria. MAIN OUTCOME MEASUREMENTS: En bloc
      resection, en bloc tumor-free margin resection, and curative resection rates were
      98%, 93%, and 83%, respectively. The delayed bleeding rate was 7%, and the
      perforation rate was 4%. RESULTS: The mean patient age was 67 years, and the mean
      tumor size was 19.8 mm, with 54% of the lesions located in the lesser curvature.
      The median procedure time was 61 minutes, with ESD procedures 60 minutes or
      longer associated with submucosal fibrosis (P < .001) and tumor size 25 mm or
      larger (P = .03). In every ESD procedure, both circumferential incision and
      submucosal dissection were performed by using a single knife. Two of the 4
      delayed bleeding cases required surgery, and all perforations were successfully
      managed by using endoscopic clips. LIMITATION: Long-term outcome data are
      currently unavailable. CONCLUSION: ESD for differentiated EGC resulted in
      favorable therapeutic outcomes in a Western endoscopy setting comparable to those
      achieved at major Japanese institutions.

PMID- 25952088
TI  - African Americans should be screened at an earlier age for colorectal cancer.
AB  - BACKGROUND: African Americans (AAs) have been shown to exhibit a higher incidence
      of colorectal cancer and experience lower survival compared with whites. There is
      disagreement regarding the age at which to initiate screening in AAs. OBJECTIVES:
      To calculate the age-specific incidence in AAs compared with whites while
      controlling for differences in socioeconomic status (SES) and to calculate the
      joinpoint at which the incidence begins to increase in each race. DESIGN:
      Retrospective database review. SETTING: Surveillance, Epidemiology, and End
      Results database. PATIENTS: All patients with adenocarcinoma of the colon or
      rectum from 2000 through 2011 in the SEER 18 database. INTERVENTIONS: We
      calculated the joinpoint of the upward trend of the age-adjusted incidence rate
      to determine the age at which the slope of the incidence curve began to increase
      in each race, while controlling for differences in SES by using a composite
      socioeconomic index. MAIN OUTCOME MEASUREMENTS: Age-adjusted incidence of colon
      and rectal cancer. RESULTS: The age-specific incidence of colorectal cancer
      (cases per 100,000 population) was 0.3 versus 0.4 in whites compared with AAs at
      20 years of age. At 50 years of age, the incidence was 44.2 compared with 62.6 in
      whites compared with AAs. The model indicated a joinpoint at 47 years of age for
      whites (95% confidence interval, 45-49) and 43 for AAs (95% confidence interval,
      42-45) (P < .001.) When SES was considered in stratification, joinpoints for
      whites were 48, 47, and 46 at high, middle, and low SES, respectively.
      Conversely, joinpoints of 43, 44, and 42 in the corresponding SES for AAs were
      noted (P <= .001). LIMITATIONS: There was no intervention, and we cannot conclude
      that changing screening policy would affect this disparity. CONCLUSION: There is
      a disparity in the age-specific incidence of colorectal cancer in AAs compared
      with whites beginning at 45 years of age. These differences persist across
      socioeconomic strata.

PMID- 25952089
TI  - A new descriptor for computer-aided diagnosis of EUS imaging to distinguish
      autoimmune pancreatitis from chronic pancreatitis.
AB  - BACKGROUND AND AIMS: Computer-aided diagnosis of EUS images was quite useful in
      differentiating pancreatic cancer from normal tissue and chronic pancreatitis.
      This study investigated the feasibility of using computer-aided diagnostic
      techniques to extract EUS image parameters to distinguish autoimmune pancreatitis
      from chronic pancreatitis. METHODS: A new descriptor, local ternary pattern
      variance, was introduced to improve the performance of the classification model.
      Patients with autoimmune pancreatitis (n = 81) or chronic pancreatitis (n = 100)
      were recruited for this study. Representative EUS images were selected, and 115
      parameters from 10 categories were extracted from the region of interest.
      Distance-between-class and sequential forward selection algorithms were used for
      their ideal combination of features that allowed a support vector machine
      predictive model to be built, trained, and validated. The accuracy, sensitivity,
      specificity, positive predictive values (PPVs), and negative predictive values
      (NPVs) were used to evaluate the performance of experimental results. RESULTS:
      Fourteen parameters from 3 categories were selected as an ideal combination of
      features. The sample set was randomly divided into a training set and a testing
      set by using two different algorithms-the leave-one-out algorithm and the half
      and-half method. The half-and-half method yielded an average (+/- standard
      deviation) accuracy of 89.3 +/- 2.7%, sensitivity of 84.1 +/- 6.4%, specificity
      of 92.5 +/- 3.3%, PPV of 91.6 +/- 3.7%, and NPV of autoimmune pancreatitis of
      88.0 +/- 4.1%. CONCLUSIONS: This study shows that, with the local ternary pattern
      variance textural feature, computer-aided diagnosis of EUS imaging may be
      valuable to differentiate autoimmune pancreatitis from chronic pancreatitis.
      Further refinement of such models could generate tools for the clinical diagnosis
      of autoimmune pancreatitis.

PMID- 25952090
TI  - Safety experience with the duodenal-jejunal bypass liner: an endoscopic treatment
      for diabetes and obesity.
AB  - BACKGROUND: The duodenal-jejunal bypass liner (DJBL) is a new, device-based
      endoscopic treatment for type 2 diabetes mellitus (T2DM) and obesity. OBJECTIVE:
      To report serious safety events of subjects treated with the DJBL while offering
      a simple guideline to mitigate risk. DESIGN: Single-center observational study.
      SETTING: Tertiary referral center. PATIENTS: For commercial use, patients were
      eligible for implantation of the DJBL when they met the following criteria: age
      18 to 65 years, body mass index 28 to 45 kg/m(2), T2DM, and negative serum
      Helicobacter pylori test. INTERVENTIONS: Endoscopic implantation of the DJBL.
      MAIN OUTCOME MEASUREMENTS: Adverse events, serious adverse events, early
      explantation. RESULTS: Between October 2007 and January 2014, 152 of 165 planned
      implantations (92%) and 94 explantations were performed in our center.
      Significant weight loss and improvement in T2DM and other cardiovascular
      parameters were achieved. Early removal of the device occurred because of
      persistent GI symptoms in 16 patients (11%). Serious adverse events were observed
      in a subset of patients: 7 GI bleeds, 5 of which required early removal; 2 cases
      of pancreatitis; 1 case of hepatic abscess; and 1 obstruction of the sleeve.
      Explantation resulted in an esophageal tear in 2 cases. LIMITATIONS: Single
      center study. CONCLUSION: The DJBL improves glycemic control while causing weight
      loss. The safety profile of the DJBL demonstrates a reasonable tolerability
      profile. However, serious safety adverse events can occur. Patient selection,
      expert use of the device at placement and removal, and the supportive care of an
      experienced multidisciplinary team are key for safe and effective use of the
      DJBL.

PMID- 25952091
TI  - Rate of duodenal-biliary reflux increases in patients with recurrent common bile
      duct stones: evidence from barium meal examination.
AB  - BACKGROUND: Stone recurrence is a common late adverse event after ERCP in
      patients with common bile duct stones (CBDS). Duodenal-biliary reflux (DBR) is
      considered a major cause of CBDS recurrence. However, specific evidence is still
      lacking. OBJECTIVE: To investigate the DBR rate in patients with recurrent CBDS
      after ERCP. DESIGN: A prospective case-control study. SETTING: A tertiary center.
      PATIENTS: During follow-up, patients with a history of either recurrent CBDS
      (recurrence group) or nonrecurrent CBDS (control group) were invited to
      participate in the study. All patients had previously undergone successful CBDS
      removal by ERCP. Patients in the control group were matched with the recurrence
      group by age and gender in a 1:1 ratio. Patients with gallbladder stones,
      hepatolithiasis, remnant CBDS, CBD strictures, or stents were excluded.
      INTERVENTIONS: Standard barium meal examination, MRCP, and enhanced abdominal CT.
      MAIN OUTCOME MEASUREMENTS: DBR. RESULTS: Thirty-two patients with a history of
      recurrent CBDS and 32 matched control subjects were enrolled. Baseline
      characteristics and parameters regarding the first ERCP were comparable between
      the 2 groups. The DBR rate was significantly higher in the recurrent than in the
      control group (68.8% vs 15.6%, P < .001). Multivariate analysis indicated that
      DBR (OR, 9.59; 95% CI, 2.65-34.76) and acute distal CBD angulation (OR, 5.48; 95%
      CI, 1.52-19.78) were independent factors associated with CBDS recurrence. DBR
      rates in patients with no, single, or multiple recurrences were 15.6%, 60.9%, and
      88.9%, respectively (P < .001). Intrahepatic bile duct reflux was more common in
      patients with multiple recurrences. LIMITATIONS: Small sample size. CONCLUSIONS:
      DBR is correlated with CBDS recurrence in patients who had previously undergone
      ERCP. DBR and acute distal CBD angulation are 2 independent risk factors related
      to stone recurrence. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT02329977.)

PMID- 25952092
TI  - The association of colonoscopy quality indicators with the detection of screen
      relevant lesions, adverse events, and postcolonoscopy cancers in an asymptomatic
      Canadian colorectal cancer screening population.
AB  - BACKGROUND: Although several quality indicators of colonoscopy have been defined,
      quality assurance activities should be directed at the measurement of quality
      indicators that are predictive of key screening colonoscopy outcomes. OBJECTIVE:
      The goal of this study was to examine the association among established quality
      indicators and the detection of screen-relevant lesions (SRLs), adverse events,
      and postcolonoscopy cancers. DESIGN: Historical cohort study. SETTING: Canadian
      colorectal cancer screening center. PATIENTS: A total of 18,456 asymptomatic men
      and women ages 40 to 74, at either average risk or increased risk for colorectal
      cancer because of a family history, who underwent a screening colonoscopy from
      2008 to 2010. MAIN OUTCOME MEASUREMENTS: Using univariate and multivariate
      analyses, we explored the association among procedural quality indicators and 3
      colonoscopy outcomes: detection of SRLs, adverse events, and postcolonoscopy
      cancers. RESULTS: The crude rates of SRLs, adverse events, and postcolonoscopy
      cancers were 240, 6.44, and .54 per 1000 colonoscopies, respectively. Several
      indicators, including endoscopist withdrawal time (OR, 1.3; 95% CI, 1.2-1.4) and
      cecal intubation rate (OR, 13.9; 95% CI, 1.9-96.9), were associated with the
      detection of SRLs. No quality indicator was associated with the risk of adverse
      events. Endoscopist average withdrawal time over 6 minutes (OR, .12; 95% CI, .002
      .85) and SRL detection rate over 20% (OR, .17; 95% CI, .03-.74) were associated
      with a reduced risk of postcolonoscopy cancers. LIMITATIONS: Single-center study.
      CONCLUSION: Quality assurance programs should prioritize the measurement of
      endoscopist average withdrawal time and adenoma (SRL) detection rate.

PMID- 25952093
TI  - Endoscopic gallbladder drainage compared with percutaneous drainage.
AB  - BACKGROUND: High-risk patients with cholecystitis have conventionally been
      offered percutaneous gallbladder drainage (PGBD) for treatment. A growing
      experience of endoscopic gallbladder drainage (EGBD) has been reported to be
      effective and safe. OBJECTIVE: To compare the short- and long-term outcomes of
      EGBD and PGBD. DESIGN: A retrospective review. SETTING: Single academic tertiary
      care center. PATIENTS: Inpatients diagnosed with cholecystitis. INTERVENTIONS:
      Any patient deemed a nonsurgical candidate and who has undergone either PGBD or
      EGBD was included in the analysis. MAIN OUTCOME MEASUREMENTS: Patient
      demographics along with procedural and clinical outcomes were recorded for each
      group. RESULTS: Forty-three patients underwent PGBD and 30 underwent EGBD (24
      transpapillary, 6 transmural). Technical (97.6% vs 100%) and clinical (97.6% vs
      86.7%) success rates of PGBD and EGBD were similar. However, postprocedure
      hospital length of stay (16.3 vs 7.6 days), time to clinical resolution (4.6 vs
      3.0 days), adverse event rate (39.5% vs 13.3%), number of sessions (2.0 vs 1.0),
      number of repeat interventions (53.4% vs 13.3%), and postprocedure pain scores
      (3.8 vs 2.1) were significantly higher for PGBD than EGBD. LIMITATIONS:
      Retrospective analysis. CONCLUSION: Although EGBD has similar technical and
      clinical success compared with PGBD, it uses fewer hospital resources and results
      in fewer adverse events, improved pain scores, and decreased need for repeat
      gallbladder drainage. EGBD may provide a less-invasive, safer, cost-effective
      option for gallbladder drainage than PGBD with improved clinical outcomes.

PMID- 25952094
TI  - Colon cancer arising from a sessile serrated adenoma/polyp detected on positron
      emission tomography/computed tomography.

PMID- 25952095
TI  - Primary cutaneous natural killer/T-cell lymphoma of the nasal type: a report of 4
      cases in North American patients.
AB  - The "nasal" type of primary cutaneous lymphoma with natural killer/T-cell
      differentiation is rarely encountered outside Asia. The authors herein document 4
      cases in White, North American individuals between the ages of 39 and 73 years.
      Their skin lesions were located on the legs in 2 cases, and they were multifocal
      in the other 2 patients. Microscopically, each neoplasm manifested as a dense
      infiltrate of cytologically aberrant lymphocytes in the dermis and subcutis. The
      lesional cells were angiocentric, with associated infarctive-type necrosis of the
      surrounding tissue. All tumors were labeled for CD3 and CD56; 3 also expressed T
      cell intracellular antigen 1. Chromogenic in situ hybridization was intensely
      reactive for Epstein-Barr virus-encoded ribonucleic acid in each case. All
      patients died of their tumors or were likely to do so. The pathologic
      differential diagnosis of "nasal-type" natural killer/T-cell lymphoma in the skin
      principally centers on gamma-delta T-cell lymphoma and subcutaneous panniculitis
      like T-cell lymphoma. Integrated analysis of histologic, immunohistochemical,
      genotypic, and in situ hybridization data is necessary to separate these entities
      from one another. 

PMID- 25952096
TI  - Effects of ROCK inhibitor Y-27632 on cell fusion through a microslit.
AB  - We previously reported a direct cytoplasmic transfer method using a microfluidic
      device, in which cell fusion was induced through a microslit (slit-through
      fusion) by the Sendai virus envelope (HVJ-E) to prevent nuclear mixing. However,
      the method was impractical due to low efficiency of slit-through-fusion formation
      and insufficient prevention of nuclear mixing. The purpose of this study was to
      establish an efficient method for inducing slit-through-fusion without nuclear
      mixing. We hypothesized that modulation of cytoskeletal component can decrease
      nuclear migration through the microslit considering its functions. Here we report
      that supplementation with Y-27632, a specific ROCK inhibitor, significantly
      enhances cell fusion induction and prevention of nuclear mixing. Supplementation
      with Y-27632 increased the formation of slit-through-fusion efficiency by more
      than twofold. Disruption of F-actin by Y-27632 prevented nuclear migration
      between fused cells through the microslit. These two effects of Y-27632 led to
      promotion of the slit-through-fusion without nuclear mixing with a 16.5-fold
      higher frequency compared to our previous method (i.e., cell fusion induction by
      HVJ-E without supplementation with Y-27632). We also confirmed that mitochondria
      were successfully transferred to the fusion partner under conditions of Y-27632
      supplementation. These findings demonstrate the practicality of our cell fusion
      system in producing direct cytoplasmic transfer between live cells.

PMID- 25952098
TI  - The current dialogue between phenomenology and psychiatry: a problematic
      misunderstanding.
AB  - A revival of the dialogue between phenomenology and psychiatry currently takes
      place in the best international journals of psychiatry. In this article, we
      analyse this revival and the role given to phenomenology in this context.
      Although this dialogue seems at first sight interesting, we show that it is
      problematic. It leads indeed to use phenomenology in a special way, transforming
      it into a discipline dealing with empirical facts, so that what is called
      "phenomenology" has finally nothing to do with phenomenology. This so-called
      phenomenology tallies however with what we have always called semiology. We try
      to explain the reasons why phenomenology is misused in that way. In our view,
      this transformation of phenomenology into an empirical and objectifying
      discipline is explained by the role attributed to phenomenology by contemporary
      authors, which is to solve the problems raised by the Diagnostic and Statistical
      Manual of Mental Disorders. 

PMID- 25952097
TI  - Serodiagnosis of Toxoplasma gondii infection in bovines from Kerala, India using
      a recombinant surface antigen 1 ELISA.
AB  - Data on the prevalence of toxoplasmosis in farm animals from India is scanty.
      Though a few reports exist on prevalence of toxoplasmosis in small ruminants,
      information on toxoplasmosis in large ruminants is virtually nonexistent from
      India. An antibody detection recombinant ELISA specific for Toxoplasma gondii was
      laboratory standardized using recombinant surface antigen 1 (SAG1) protein. A 958
      bp truncated sequence coding for tachyzoite stage specific SAG1 protein was
      amplified and expressed in Escherichia coli BL21(DE3) cells. A high-level
      expression of the histidine-tagged thioredoxin fusion protein was obtained after
      8 h of incubation. The recombinant protein was affinity purified by Ni-NTA
      agarose chromatography and characterized by SDS-PAGE and Western blot.
      Subsequently, the diagnostic potential of the recombinant protein was assessed
      with 258 cattle sera samples from field by a laboratory standardized recSAG1
      ELISA. Sera from 71.8% of the cattle showed sero positivity for T. gondii
      specific IgG. The sensitivity and specificity of the recSAG1 ELISA were 84.38%
      and 87.88%, respectively in comparison to indirect fluorescent antibody test
      (IFAT). This is the first report on sensitive serodetection of Toxoplasma
      infection in bovines from India.

PMID- 25952099
TI  - IL-18, TNF, and IFN-gamma alleles and genotypes are associated with
      susceptibility to chronic hepatitis B infection and severity of liver injury.
AB  - This study evaluated the association of polymorphisms in the IL-18 (-607C/A and 
      137C/G), IFNgamma (+874 A/T), and TNF (-238 A/G and -308 A/G) genes with
      susceptibility to HBV infection and severity of liver injury. A total of 259
      chronic HBV-infected patients followed at the University Hospital, Faculty of
      Medicine of Ribeirao Preto, Sao Paulo, Brazil, and 202 healthy individuals were
      studied. Four Single Nucleotide Polymorphisms (SNPs) were amplified by Polymerase
      Chain Reaction (PCR). Liver biopsy was performed in 212 HBV-infected patients and
      classified according to severity of liver fibrosis (scores 0-4) and
      necroinflammatory activity (HAI scores 0-18). TNF-308*A allele (P < 0.001; OR =
      2.16) and TNF -308 AA genotype (P = 0.026; OR = 5.43) were associated with
      susceptibility to HBV infection. An association was found between severe liver
      fibrosis when compared to mild fibrosis and the following polymorphisms: Alleles
      IL-18 -137*G (P = 0.004; OR = 3.45), TNF -308*A (P < 0.001; OR = 3.39), and
      IFNgamma +874*T (P = 0.029; OR = 1.85) and IL-18 -137 GG genotype (P = 0.009; OR
      = 3.70). No significant association was found between IL-18 (-607 A/C)
      polymorphism and severity of liver fibrosis. Alleles IL-18 -137*G (P = 0.028; OR
      = 2.64) and TNF-308*A (P = 0.002; OR = 3.06) and IL-18 -137 GG genotype (P =
      0.011; OR = 4.20) were associated with severe necroinflammatory activity (HAI>12)
      when compared to mild necroinflammatory activity (HAI 1-8). The results suggest
      that IL-18 -137C/G, TNF-308 G/A and IFNgamma +874 A/T SNPs were associated to
      more severe liver injury in chronic HBV infection. TNF -308*A allele and TNF -308
      AA genotype could play a role in the susceptibility to HBV infection.

PMID- 25952100
TI  - Diabetes and Technology: A Revolution on Our Doorstep, but Let's Keep Humanity at
      the Bedside.

PMID- 25952101
TI  - Next-Generation Genotyping by Digital PCR to Detect and Quantify the BRAF V600E
      Mutation in Melanoma Biopsies.
AB  - The detection of the BRAF V600E mutation in melanoma samples is used to select
      patients who should respond to BRAF inhibitors. Different techniques are
      routinely used to determine BRAF status in clinical samples. However, low tumor
      cellularity and tumor heterogeneity can affect the sensitivity of somatic
      mutation detection. Digital PCR (dPCR) is a next-generation genotyping method
      that clonally amplifies nucleic acids and allows the detection and quantification
      of rare mutations. Our aim was to evaluate the clinical routine performance of a
      new dPCR-based test to detect and quantify BRAF mutation load in 47 paraffin
      embedded cutaneous melanoma biopsies. We compared the results obtained by dPCR
      with high-resolution melting curve analysis and pyrosequencing or with one of the
      allele-specific PCR methods available on the market. dPCR showed the lowest limit
      of detection. dPCR and allele-specific amplification detected the highest number
      of mutated samples. For the BRAF mutation load quantification both dPCR and
      pyrosequencing gave similar results with strong disparities in allele frequencies
      in the 47 tumor samples under study (from 0.7% to 79% of BRAF V600E
      mutations/sample). In conclusion, the four methods showed a high degree of
      concordance. dPCR was the more-sensitive method to reliably and easily detect
      mutations. Both pyrosequencing and dPCR could quantify the mutation load in
      heterogeneous tumor samples. 

PMID- 25952102
TI  - Sulfated Polysaccharide Isolated from the Sea Cucumber Stichopus japonicus
      Against PC12 Hypoxia/Reoxygenation Injury by Inhibition of the MAPK Signaling
      Pathway.
AB  - In this report, the sulfated polysaccharide (SJP) isolated from the sea cucumber
      Stichopus japonicus can protect PC12 from Na2S2O4-induced hypoxia/reoxygenation
      (H/R) injury. SJP effectively improves cell viability and reduces extracellular
      LDH release in PC12 cells after H/R. Moreover, SJP significantly increases SOD
      activity but decreases MDA levels. Our experiments showed that SJP could
      significantly reduce cell apoptosis caused by H/R. Our current results
      demonstrate that SJP suppressed the activation of MAPKs, resulting in a
      significant decrease in Bax/Bcl-2 ratio, cleaved caspase-3/caspase-3, p53
      phosphorylation, and cytochrome c release in a concentration-dependent manner.
      MAPK is closely related to H/R injury. SJP inhibited JNK1/2 and p38 MAPK
      activation but did not affect the increased ERK1/2 expression. These results
      suggested that JNK1/2 and p38 MAPK pathways could be involved in SJP-mediated
      attenuation of PC12 H/R injury. SJP prevented PC12 H/R injury in a dose-dependent
      manner, indicating that SJP may be developed as a candidate drug to prevent or
      treat cerebral ischemia-reperfusion injury. 

PMID- 25952103
TI  - Establish an automated flow injection ESI-MS method for the screening of fragment
      based libraries: Application to Hsp90.
AB  - ESI-MS is a well established technique for the study of biopolymers (nucleic
      acids, proteins) and their non covalent adducts, due to its capacity to detect
      ligand-target complexes in the gas phase and allows inference of ligand-target
      binding in solution. In this article we used this approach to investigate the
      interaction of ligands to the Heat Shock Protein 90 (Hsp90). This enzyme is a
      molecular chaperone involved in the folding and maturation of several proteins
      which has been subjected in the last years to intensive drug discovery efforts
      due to its key role in cancer. In particular, reference compounds, with a broad
      range of dissociation constants from 40pM to 100MUM, were tested to assess the
      reliability of ESI-MS for the study of protein-ligand complexes. A good agreement
      was found between the values measured with a fluorescence polarization
      displacement assay and those determined by mass spectrometry. After this
      validation step we describe the setup of a medium throughput screening method,
      based on ESI-MS, suitable to explore interactions of therapeutic relevance
      biopolymers with chemical libraries. Our approach is based on an automated flow
      injection ESI-MS method (AFI-MS) and has been applied to screen the Nerviano
      Medical Sciences proprietary fragment library of about 2000 fragments against
      Hsp90. In order to discard false positive hits and to discriminate those of them
      interacting with the N-terminal ATP binding site, competition experiments were
      performed using a reference inhibitor. Gratifyingly, this group of hits matches
      with the ligands previously identified by NMR FAXS techniques and confirmed by X
      ray co-crystallization experiments. These results support the use of AFI-MS for
      the screening of medium size libraries, including libraries of small molecules
      with low affinity typically used in fragment based drug discovery. AFI-MS is a
      valid alternative to other techniques with the additional opportunities to
      identify compounds interacting with unpredicted or allosteric sites, without the
      need of any binding probes. 

PMID- 25952104
TI  - Nasal and pulmonary vaccine delivery using particulate carriers.
AB  - INTRODUCTION: Many human pathogens cause respiratory illness by colonizing and
      invading the respiratory mucosal surfaces. Preventing infection at local sites
      via mucosally active vaccines is a promising and rational approach for vaccine
      development. However, stimulating mucosal immunity is often challenging.
      Particulate adjuvants that can specifically target mucosal immune cells offer a
      promising opportunity to stimulate local immunity at the nasal and/or pulmonary
      mucosal surfaces. AREAS COVERED: This review analyzes the common causes of
      respiratory infections, the challenges in the induction of mucosal and systemic
      responses and current pulmonary and nasal mucosal vaccination strategies. The
      ability of various particulate adjuvant formulations, including lipid-based
      particles, polymers and other particulate systems, to be effectively utilized for
      mucosal vaccine delivery is discussed. EXPERT OPINION: Induction of antibody and
      cell-mediated mucosal immunity that can effectively combat respiratory pathogens
      remains a challenge. Particulate delivery systems can be developed to target
      mucosal immune cells and effectively present antigen to evoke a rapid and long
      term local immunity in the respiratory mucosa. In particular, particulate
      delivery systems offer the versatility of being formulated with multiple
      adjuvants and antigenic cargo, and can be tailored to effectively prime immune
      responses across the mucosal barrier. The opportunity for rational design of
      novel subunit particulate vaccines is emerging.

PMID- 25952105
TI  - Can fitness and movement quality prevent back injury in elite task force police
      officers? A 5-year longitudinal study.
AB  - Elite police work has bursts of intense physically demanding work requiring high
      levels of fitness, or capacity, and movement competency; which are assumed to
      increase one's injury resilience. The purpose of this study was to follow members
      of an elite police force (N = 53) to test whether back injuries (N = 14) could be
      predicted from measures of fitness and movement quality. Measures of torso
      endurance, relative and absolute strength, hip ROM and movement quality using the
      Functional Movement Screen(TM) and other dynamic movement tests were obtained
      from every officer at baseline. When variables were grouped and considered
      holistically, rather than individually, back injury could be predicted. Seven
      variables best predicted those who would suffer a back injury (64% sensitivity
      and 95% specificity for an overall concordance of 87%). Overall, the ability to
      predict back injury was not high, suggesting that there is more complexity to
      this relationship than is explained with the variables tested here. Practitioner
      Summary: Members of elite police forces have exposure to intense physically
      demanding work. Increased levels of fitness and movement competency have been
      assumed to increase injury resilience. However, complexity in the interactions
      between exposure, movement competency, training, fitness and injury may occlude
      the true relationship between these variables.

PMID- 25952106
TI  - Association between peripheral airway function and neutrophilic inflammation in
      asthma.
AB  - BACKGROUND AND OBJECTIVE: Small airway dysfunction is associated with asthma
      severity and control, but its association with airway inflammation is unknown.
      The aim was to determine the association between sputum inflammatory cells and
      the site of small airway dysfunction, measured by multiple breath nitrogen
      washout in convection-dependent (Scond) and more peripheral diffusion-dependent
      (Sacin) airways. METHODS: Fifty-three (20-67 years) subjects with asthma on
      inhaled corticosteroid (ICS) treatment were characterized by spirometry, Scond,
      Sacin and induced sputum differential counts. %Predicted values for Scond and
      Sacin were calculated from published reference equations to adjust for the
      effects of age. Univariate correlations were assessed using the Spearman test.
      Multivariate linear regressions were performed to account for potential
      confounders, including age, gender, disease duration, body mass index and ICS
      dose. RESULTS: Sacin (%predicted) correlated significantly with neutrophil% (rs 
      = 0.33, P = 0.02), ICS dose (rs  = -0.28, P = 0.04) and age (rs  = 0.27, P =
      0.05). In multivariate analysis, Sacin related only to neutrophil% (adjusted R(2)
      = 0.18, P = 0.001). Scond (%predicted) correlated significantly only with
      eosinophil% (rs  = 0.39, P = 0.004). There was a trend for a negative
      relationship with ICS dose (rs  = -0.26, P = 0.06). In multivariate analysis,
      Scond related to eosinophil% and ICS dose independently (adjusted R(2)  = 0.12, P
      = 0.02). CONCLUSIONS: Acinar and conductive airway dysfunction is associated with
      different inflammatory profiles in asthmatic airways, independently of the
      effects of age and disease duration. The association between acinar airway
      dysfunction and neutrophilic airway inflammation may have implications for asthma
      treatment.

PMID- 25952107
TI  - Tetramethylpyrazine inhibits CoCl2 -induced neurotoxicity through enhancement of
      Nrf2/GCLc/GSH and suppression of HIF1alpha/NOX2/ROS pathways.
AB  - Hypoxia-mediated neurotoxicity contributes to various neurodegenerative
      disorders, including Alzheimer's disease and multiple sclerosis.
      Tetramethylpyrazine (TMP), a major bioactive component purified from Ligusticum
      wallichii Franchat, exhibited potent neuroprotective effect. However, the
      mechanism of TMP-exerted neuroprotective effect against hypoxia was not clear. In
      the study, we investigated the mechanism of the neuroprotective effect of TMP
      against hypoxia induced by CoCl2 in vitro and in vivo. The results showed that
      TMP could protect against CoCl2 -induced neurotoxicity in PC12 cells and in rats,
      as evidenced by enhancement of cell viability in PC12 cells and improvement of
      learning and memory ability in rats treated with CoCl2 . TMP could inhibit
      mitochondrial dysfunction, mitochondrial apoptotic molecular events, and thus
      apoptosis induced by CoCl2 . TMP inhibited CoCl2 -increased reactive oxygen
      species (ROS) level, which may contribute to hypoxia-related neurotoxicity
      induced by CoCl2 . The antioxidant and neuroprotective activities of TMP involved
      two pathways: one was the enhancement of nuclear factor erythroid 2-related
      factor 2 (Nrf2)/catalytic subunit of gamma-glutamylcysteine ligase-mediated
      regulation of GSH and the other was the inhibition of hypoxia-inducible factor 1
      alpha/NADPH oxidase 2 (NOX2)-mediated ROS generation. These two pathways
      contributed to improvement of oxidative stress and thus the amelioration of
      apoptosis under hypoxic conditions. These results have appointed a new path
      toward the understanding of pathogenesis and TMP-related therapy of hypoxia
      related neurodegenerative diseases. We proposed two cascades for
      tetramethylpyrazine-exhibited protective effects against CoCl2 -induced
      neurotoxicity: One is enhancement of nuclear factor erythroid 2-related factor 2
      catalytic subunit of gamma-glutamylcysteine ligase-mediated regulation of
      glutathone and the other was the inhibition of hypoxia-inducible factor 1 alpha
      NADPH oxidase-2-mediated ROS generation. We think these findings should provide a
      new understanding of pathogenesis and tetramethylpyrazine-related therapy of
      hypoxia-related neurodegenerative diseases. 

PMID- 25952108
TI  - Decreasing initial telomere length in humans intergenerationally understates age
      associated telomere shortening.
AB  - Telomere length shortens with aging, and short telomeres have been linked to a
      wide variety of pathologies. Previous studies suggested a discrepancy in age
      associated telomere shortening rate estimated by cross-sectional studies versus
      the rate measured in longitudinal studies, indicating a potential bias in cross
      sectional estimates. Intergenerational changes in initial telomere length, such
      as that predicted by the previously described effect of a father's age at birth
      of his offspring (FAB), could explain the discrepancy in shortening rate
      measurements. We evaluated whether changes occur in initial telomere length over
      multiple generations in three large datasets and identified paternal birth year
      (PBY) as a variable that reconciles the difference between longitudinal and cross
      sectional measurements. We also clarify the association between FAB and offspring
      telomere length, demonstrating that this effect is substantially larger than
      reported in the past. These results indicate the presence of a downward secular
      trend in telomere length at birth over generational time with potential public
      health implications. 

PMID- 25952109
TI  - In vitro bioactivity investigations of Ti-15Mo alloy after electrochemical
      surface modification.
AB  - Titanium and its aluminum and vanadium-free alloys have especially great
      potential for medical applications. Electrochemical surface modification improves
      their surface bioactivity and stimulates osseointegration process. In this work,
      the effect of plasma electrolytic oxidation of the beta-type alloy Ti-15Mo
      surface on its bioactivity is presented. Bioactivity of the modified alloy was
      investigated by immersion in simulated body fluid (SBF). Biocompatibility of the
      modified alloys were tested using human bone marrow stromal cells (hBMSC) and
      wild intestinal strains (DV/A, DV/B, DV/I/1) of Desulfovibrio desulfuricans
      bacteria. The particles of apatite were formed on the anodized samples. Human
      BMSC cells adhered well on all the examined surfaces and expressed ALP, collagen,
      and produced mineralized matrix as determined after 10 and 21 days of culture.
      When the samples were inoculated with D. desulfuricans bacteria, only single
      bacteria were visible on selected samples. There were no obvious changes in
      surface morphology among samples. Colonization and bacterial biofilm formation
      was observed on as-ground sample. In conclusion, the surface modification
      improved the Ti-15Mo alloy bioactivity and biocompatibility and protected surface
      against colonization of the bacteria. (c) 2015 Wiley Periodicals, Inc. J Biomed
      Mater Res Part B: Appl Biomater, 104B: 903-913, 2016.

PMID- 25952110
TI  - Bacteriagenic silver nanoparticles: synthesis, mechanism, and applications.
AB  - Silver nanoparticles (AgNPs) have received tremendous attention due to their
      significant antimicrobial properties. Large numbers of reports are available on
      the physical, chemical, and biological syntheses of colloidal AgNPs. Since there
      is a great need to develop ecofriendly and sustainable methods, biological
      systems like bacteria, fungi, and plants are being employed to synthesize these
      nanoparticles. The present review focuses specifically on bacteria-mediated
      synthesis of AgNPs, its mechanism, and applications. Bacterial synthesis of extra
      and intracellular AgNPs has been reported using biomass, supernatant, cell-free
      extract, and derived components. The extracellular mode of synthesis is preferred
      over the intracellular mode owing to easy recovery of nanoparticles. Silver
      resistant genes, c-type cytochromes, peptides, cellular enzymes like nitrate
      reductase, and reducing cofactors play significant roles in AgNP synthesis in
      bacteria. Organic materials released by bacteria act as natural capping and
      stabilizing agents for AgNPs, thereby preventing their aggregation and providing
      stability for a longer time. Regulation over reaction conditions has been
      suggested to control the morphology, dispersion, and yield of nanoparticles.
      Bacterial AgNPs have anticancer and antioxidant properties. Moreover, the
      antimicrobial activity of AgNPs in combination with antibiotics signifies their
      importance in combating the multidrug-resistant pathogenic microorganisms.
      Multiple microbicidal mechanisms exhibited by AgNPs, depending upon their size
      and shape, make them very promising as novel nanoantibiotics. 

PMID- 25952111
TI  - Engineered biosynthesis of pimaricin derivatives with improved antifungal
      activity and reduced cytotoxicity.
AB  - Pimaricin is an important antifungal antibiotic for antifungal therapy and
      prevention of mould contamination in the food industry. In this study, three new
      pimaricin derivatives, 12-decarboxy-12-methyl pimaricin (1), 4,5-desepoxy-12
      decarboxy-12-methyl pimaricin (2), and 2-hydro-3-hydroxy-4,5-desepoxy-12
      decarboxy-12-methyl pimaricin (3), were generated through the inactivation of
      P450 monooxygenase gene scnG in Streptomyces chattanoogensis L10. Compared with
      pimaricin, 1 displayed a twofold increase in antifungal activity against Candida
      albicans ATCC 14053 and a 4.5-fold decrease in cytotoxicity with erythrocytes,
      and 2 had comparable antifungal activity and reduced cytotoxicity, whereas 3
      showed nearly no antifungal and hemolytic activities. Genetic and biochemical
      analyses proved that 1 is converted from 2 by P450 monooxygenase ScnD. Therefore,
      the overexpression of scnD in scnG-null strain eliminated the accumulation of 2
      and improved the yield of 1 by 20 %. Conversely, scnG/scnD double mutation
      abolished the production of 1 and improved the yield of 2 to 2.3-fold. These
      results indicate that the pimaricin derivatives with improved pharmacological
      properties obtained by genetic engineering can be further developed into
      antifungal agents for potential clinical application.

PMID- 25952112
TI  - Biomarkers for infection: enzymes, microbes, and metabolites.
AB  - Wound infection is a severe complication causing delayed healing and risks for
      patients. Conventional methods of diagnosis for infection involve error-prone
      clinical description of the wound and time-consuming microbiological tests. More
      reliable alternatives are still rare, except for invasive and unaffordable gold
      standard methods. This review discusses the diversity of new approaches for wound
      infection determination. There has been progress in the detection methods of
      microorganisms, including the assessment of the diversity of the bacterial
      community present in a wound, as well as in the elaboration of specific markers.
      Another interesting strategy involves the quantification of enzyme activities in
      the wound fluid secreted by the immune system as response to infection. Color
      changing substrates for these enzymes consequently have been shown to allow
      detection of an infection in wounds in a fast and easy way. Promising results
      were also delivered in measuring pH changes or detecting enhanced amounts of
      volatile molecules in case of infection. A simple and effective infection
      detection tool is not yet on the market, but innovative ideas pave the way for
      the investigation of fast and easy point-of-care devices. 

PMID- 25952113
TI  - Multienzymatic synthesis of nucleic acid derivatives: a general perspective.
AB  - Living cells are most perfect synthetic factory. The surprising synthetic
      efficiency of biological systems is allowed by the combination of multiple
      processes catalyzed by enzymes working sequentially. In this sense, biocatalysis
      tries to reproduce nature's synthetic strategies to perform the synthesis of
      different organic compounds using natural catalysts such as cells or enzymes.
      Nowadays, the use of multienzymatic systems in biocatalysis is becoming a
      habitual strategy for the synthesis of organic compounds that leads to the
      realization of complex synthetic schemes. By combining several steps in one pot,
      a significant step economy can be realized and the potential for environmentally
      benign synthesis is improved. Using this sustainable synthetic system, several
      work-up steps can be avoided and pure products are ideally isolated after a
      series of reactions in one single vessel after just one straightforward
      purification step. In recent years, enzymatic methodology for the preparation of
      nucleic acid derivatives (NADs) has become a standard technique for the synthesis
      of a wide variety of natural NADs. Enzymatic methods have been shown to be an
      efficient alternative for the synthesis of nucleoside and nucleotide analogs to
      the traditional multistep chemical methods, since chemical glycosylation
      reactions include several protection-deprotection steps and the use of chemical
      reagents and organic solvents that are expensive and environmentally harmful. In
      this minireview, we want to illustrate what we consider the most current relevant
      examples of in vivo and in vitro multienzymatic systems used for the synthesis of
      nucleic acid derivatives showing advantages and disadvantages of each
      methodology. Finally, a detailed perspective about the impact of -omics in
      multienzymatic systems has been described. 

PMID- 25952114
TI  - Antimicrobial and osteogenic properties of silver-ion-implanted stainless steel.
AB  - Prevention of implant loosening and infection is crucial to orthopedic and dental
      surgeries. In this work, the surface of stainless steel (SS) was modified by
      silver-sourced plasma immersion ion implantation (Ag-PIII). Metallic silver
      nanoparticles with various diameters and distributions were fabricated on the SS
      surfaces after treatment with Ag-PIII for 0.5 and 1.5 h, respectively. The
      osteogenic activity and antimicrobial properties of SS before and after Ag-PIII
      treatment were evaluated using in vitro and in vivo tests. The results
      demonstrated that Ag-PIII treatment not only promoted the antibacterial activity
      of SS but also enhanced the osteogenic differentiation of human bone marrow
      stromal cells. 

PMID- 25952115
TI  - Psychopharmacological treatment differences in autogenous and reactive
      obsessions: A retrospective chart review.
AB  - BACKGROUND: Identification of homogeneous subgroups of obsessive compulsive
      disorder (OCD) patients may have important implications for improving effective
      treatment options. It has been proposed that obsessive thoughts can be classified
      into two subtypes, i.e. autogenous and reactive obsessions. Although it has been
      shown that patients with autogenous obsessions may display a worse response to
      treatment, no studies have yet addressed whether there is a different need for
      the psychopharmacological treatment options in the subtypes of OCD patients. AIM:
      To investigate the clinical characteristics and treatment differences between
      autogenous (A-OCD) and reactive (R-OCD) subtypes of OCD patients. METHODS: Both
      OCD subgroups (n = 50 for A-OCD, n = 130 for R-OCD) were compared with each other
      in terms of their demographic and clinical parameters. Odds ratio values for
      gender, treatment options, co-morbidity, severity of OCD, and response to
      treatment were computed. Multivariate hierarchical regression analyses were
      performed to identify any predictors for treatment options, severity of OCD, and
      response to treatment. RESULTS: Our results indicated that the A-OCD and R-OCD
      groups differed from each other on some demographic and clinical variables in
      addition to their psychopharmacological treatment needs. Patients in the A-OCD
      group were found to be prescribed an atypical antipsychotic 2.3 times more likely
      than the R-OCD group. The odds for a combination treatment, or the improvement of
      OCD symptoms from baseline levels did not differ between the two subtypes of
      obsession groups. CONCLUSIONS: Autogenous and reactive subtypes of obsessions may
      need to be offered different psychopharmacological treatment options.

PMID- 25952116
TI  - The evolution of concepts in laparoscopic cholecystectomy in a general surgical
      clinic from Timisoara, Romania.
AB  - AIM: The analysis of the progress in the gallbladder laparoscopic surgery by
      comparing the cases operated after the implementation of this procedure in
      General Surgery Clinic I of Emergency County Hospital Timisoara, Romania to the
      current period. MATERIAL AND METHODS: Two groups of 1000 patients undergoing
      laparoscopic cholecystectomies have been studied. The first group has been
      operated between 1994 and 1998, the second group between 2008 and 2011. Analyzed
      data: surgical indications, the rate of conversions to conventional surgery,
      intraoperative accidents, postoperative complications and the death rate.
      RESULTS: The indications for a laparoscopic approach have been extended from 53 %
      (530 cases) of the total number of cholecystectomies to 78%(780 cases). The rate
      of conversions has decreased from 4.9% (26 cases) to 3% (23 cases). The number of
      patients with acute cholecystitis operated with laparoscopic approach has risen
      from 48.30 % (256 cases) to 73.07 % (570 cases). The intraoperative accidents and
      the postoperative complications rate remained unchanged. There were no registered
      deaths CONCLUSIONS: The comparative study has demonstrated the positive evolution
      of the laparoscopic method due to surgical technique improvement and
      technological progress. The laparoscopic cholecystectomy is "the gold standard"
      as an ablation procedure of the gallbladder.

PMID- 25952117
TI  - Growth of Bacillus methanolicus in 2 M methanol at 50  degrees C: the effect of
      high methanol concentration on gene regulation of enzymes involved in
      formaldehyde detoxification by the ribulose monophosphate pathway.
AB  - Bacillus methanolicus MGA3 is a Gram-positive aerobic methylotroph growing
      optimally at 50-53 degrees C. Methylotrophy in B. methanolicus is encoded on
      pBM19 and by two chromosomal copies of the methanol dehydrogenase (mdh), hexulose
      phosphate synthase (hps) and phosphohexuloisomerase (phi) genes. However, there
      are no published studies on the regulation of methylotrophy or the dominant
      mechanism of detoxification of intracellular formaldehyde in response to high
      methanol concentration. The u max of B. methanolicus MGA3 was assessed on
      methanol, mannitol and glucose. B. methanolicus achieved a u max at 25 mM initial
      methanol of 0.65 +/- 0.007 h(-1), which decreased to 0.231 +/- 0.004 h(-1) at 2 M
      initial methanol. Slow growth was also observed with initial methanol
      concentrations of >2 M. The u max on mannitol and glucose are 0.532 +/- 0.002 and
      0.336 +/- 0.003 h(-1), respectively. Spiking cultures with additional methanol
      (100 mM) did not disturb the growth rate of methanol-grown cells, whereas, a 50
      mM methanol spike halted the growth in mannitol. Surprisingly, growth in methanol
      was inhibited by 1 mM formaldehyde, while mannitol-grown cells tolerated 2 mM.
      Moreover, mannitol-grown cells removed formaldehyde faster than methanol-grown
      cells. Further, we show that methanol oxidation in B. methanolicus MGA3 is mainly
      carried out by the pBM19-encoded mdh. Formaldehyde and formate addition down
      regulate the mdh and hps genes in methanol-grown cells. Similarly, they down
      regulate mdh genes in mannitol-grown cells, but up-regulate hps.
      Phosphofructokinase (pfk) is up-regulated in both methanol and mannitol-grown
      cells, which suggests that pfk may be a possible synthetic methylotrophy target
      to reduce formaldehyde growth toxicity at high methanol concentrations.

PMID- 25952118
TI  - Enhanced production of L-sorbose in an industrial Gluconobacter oxydans strain by
      identification of a strong promoter based on proteomics analysis.
AB  - Gluconobacter oxydans is capable of rapidly incomplete oxidation of many sugars
      and alcohols, which means the strain has great potential for industrial purposes.
      Strong promoters are one of the essential factors that can improve strain
      performance by overexpression of specific genes. In this study, a pipeline for
      screening strong promoters by proteomics analysis was established. Based on the
      procedure, a new strong promoter designated as P B932_2000 was identified in G.
      oxydans WSH-003. The promoter region was characterized based on known genome
      sequence information using BPROM. The strength of P B932_2000 was further
      assessed by analysis of enhanced green fluorescent protein (egfp) expression and
      comparison with egfp expression by two commonly used strong promoters, P E.
      coli_tufB and P G. oxydans_tufB . Both quantitative real-time PCR and
      fluorescence intensities for egfp gene expression showed that P B932_2000
      promoter is stronger than the other two. Overexpression of D-sorbitol
      dehydrogenase (sldh) by P B932_2000 in G. oxydans WSH-003 enhanced the titer and
      productivity of L-sorbose synthesis from D-sorbitol by 12.0 % and 33.3 %,
      respectively. These results showed that proteomics analysis is an efficient way
      to identify strong promoters. The isolated promoter P B932_2000 could further
      facilitate the metabolic engineering of G. oxydans. 

PMID- 25952119
TI  - Increasing succinic acid production using the PTS-independent glucose transport
      system in a Corynebacterium glutamicum PTS-defective mutant.
AB  - Succinic acid synthesized from glucose shows potential as a bio-based platform
      chemical. However, the need for a high glucose concentration, and the
      accompanying low yields, limit its industrial applications. Despite efficient
      glucose uptake by the phosphotransferase system (PTS), 1 mol of
      phosphoenolpyruvate is required for each mole of internalized glucose. Therefore,
      a PTS-defective Corynebacterium glutamicum mutant was constructed to increase
      phosphoenolpyruvate availability for succinic acid synthesis, resulting in a
      lower glucose utilization rate and slower growth. The transcriptional regulator
      iolR was also deleted to enable the PTS-defective mutant to utilize glucose via
      iolT-mediated glucose transport. Deletion of iolR and overexpression of iolT1 and
      ppgk (polyphosphate glucokinase) in the PTS-deficient C. glutamicum strain
      completely restored glucose utilization, increasing production by 11.6% and yield
      by 32.4% compared with the control. This study revealed for the first time that
      iolR represses the expression of the two glucokinase genes (glk and ppgk).

PMID- 25952120
TI  - Histone H3k9 and H3k27 Acetylation Regulates IL-4/STAT6-Mediated Igepsilon
      Transcription in B Lymphocytes.
AB  - IL-4 activates STAT6 and causes the subsequent up-regulation of Ig heavy chain
      germline Igepsilon via chromatin remodeling involved in B lymphocytes
      development. STAT6 acts as a molecular switch to regulate the higher-order
      chromatin remodeling via dynamically orchestrating co-activators (CBP/Tudor-SN)
      and co-repressors (HDAC1/PSF). Here, we demonstrated that STAT6/Tudor-SN/PSF form
      a complex, balancing the acetylation and deacetylation states to co-regulate IL
      4/STAT6 gene transcription. In addition, we confirmed that IL-4 treatment
      increased the HATs activity in Ramos cells. As "active" markers, the expression
      of H3K9ac and H3K27ac increased after treatment with IL-4. However,
      transcriptional repressors such as H3K9me3 and H3K27me3 decreased in response to
      IL-4 stimulation. Moreover, IL-4 treatment enhanced H3 acetylation at the
      Igepsilon promoter regions. Our results revealed that the Igepsilon gene
      transcription is regulated by histone modifications in the IL-4/STAT6 pathway.
      The study will provide novel insights into the pathogenesis of allergic diseases.

PMID- 25952121
TI  - Effect of Combined Manual Acupuncture and Massage on Body Weight and Body Mass
      Index Reduction in Obese and Overweight Women: A Randomized, Short-term Clinical
      Trial.
AB  - Obesity is one of the leading health risk factors worldwide and is associated
      with several other risk factors and health problems. Acupuncture is utilized to
      treat a variety of health problems, one of which is obesity. Fifty-six obese
      women with body mass index (BMI) >=25 kg/m(2) were recruited for this trial and
      were randomly divided into two groups, one with combined manual acupuncture and
      massage therapy (MAMT), and the other with only manual acupuncture therapy (MAT).
      In addition, 40 overweight women with BMI 23-25 kg/m(2) were randomly divided
      into two groups, one with MAMT and the other with MAT. Therapy was carried out
      once per day for 21 days, and the body weights and the BMIs were recorded every
      day. The results showed that both MAMT and MAT could reduce body weight and BMI
      significantly, compared with the pretreatment values, for all the participants (p
      < 0.001); however, the differences in body weight and BMI reductions between pre-
      and posttreatment for the MAMT and the MAT groups were not statistically
      significant. The optimal periods for reductions in both body weight and in BMI
      were the first 4 days. Accounting for the economic strategy (time and money) in
      alternative therapy, MAT alone may present a reasonable option in the treatment
      of overweight and obesity in adults. 

PMID- 25952122
TI  - Repeated electroacupuncture in obese Zucker diabetic fatty rats: adiponectin and
      leptin in serum and adipose tissue.
AB  - Fasted, male, obese, Zucker, diabetic fatty rats aged 10-16 weeks were
      anesthetized with 1% halothane in nitrous oxide-oxygen (3:1) on alternate
      weekdays over 2 weeks. Group 1 (n = 4) did not receive electroacupuncture
      (controls); Group 2 (n = 4) received electroacupuncture using the Zhongwan and
      the Guanyuan acupoints; Group 3 (n = 4) received electroacupuncture using the
      bilateral Zusanli acupoints; Group 4 (n = 6) received neither halothane in
      nitrous oxide:oxygen nor electroacupuncture. At the end of study, animals were
      injected with sodium pentobarbitone (60 mg/mL, i.p.), and blood and white adipose
      tissue were collected. Analysis of variance and Duncan's tests showed that the
      mean leptin in serum was significantly lower and the adiponectin:leptin ratio was
      significantly higher in Group 2 than in Group 1 (p < 0.05); for Group 4, the
      serum leptin was significantly higher than it was for Groups 1-3 (p < 0.05), and
      the adiponectin:leptin ratio was significantly lower than it was for Group 2 (p <
      0.05). Similar changes occurred for the leptin levels in the pelvic adipose
      tissue. In addition, for Group 2, the mean serum insulin: glucose ratio was
      significantly higher than it was for Group 1 (p < 0.05); for Group 4 the mean
      serum insulin and insulin: glucose ratio were significantly higher than they were
      for Groups 1 and 3 (p < 0.05), but not Group 2 (p > 0.05). No significant
      differences in the serum or the adipose-tissue measurements between Groups 1 and
      3 were observed (p > 0.05). 

PMID- 25952123
TI  - Repeated electroacupuncture: an effective treatment for hyperglycemia in a rat
      model.
AB  - The effect of electroacupuncture (EA) in lowering blood glucose (BG) in eight
      fasted male obese Zucker diabetic rats aged 21-24 weeks was investigated. Group 1
      (n = 4) received no EA and Group 2 (n = 4) received EA at the Zhongwan and
      Guanyuan acupoints on Day 1, Day 3, Day 6, Day 8, and Day 10. The BG level of the
      rats was measured at 10 minutes and 20 minutes after their nose had been inserted
      into the nose cone of an anesthetic apparatus; then, EA was applied for 30
      minutes, and BG was measured again. At the end of the study, the animals were
      injected with sodium pentobarbitone (60 mg/mL, intraperitoneally), and blood and
      white adipose tissue were collected. On statistical analysis, Group 2 showed a
      significant decrease in mean BG at 20 minutes (baseline) and 50 minutes on Day 8
      and Day 10 compared with Day 1 and Day 3, but such a decrease was not observed in
      Group 1. For Group 2, the baseline BG and the change in BG over 30 minutes were
      significantly lower on Day 8 and Day 10 compared with Day 1, Day 3, and Day 6,
      but not for Group 1. No significant differences were noted between the groups in
      serum insulin, glucose, insulin-to-glucose ratio, adiponectin, leptin,
      adiponectin-to-leptin ratio, and white adipose tissue. 

PMID- 25952124
TI  - Evaluation of heat transfer in acupuncture needles: convection and conduction
      approaches.
AB  - Originating in ancient China, acupuncture using needles has been developed for
      thousands of years and has received attention for its reported medical remedies,
      such as pain relief and chronic disease treatment. Heat transfer through the
      needles, which might have effects on the biomechanism of acupuncture, providing a
      stimulus and regulating homeostasis, has never been studied. This article
      analyzes the significance of heat transfer through needles via convection and
      conduction, approached by means of computational analysis. The needle is a
      cylindrical body, and an axis symmetrical steady-state heat-transfer model that
      viscosity and static pressure was not applied. This article evaluates heat
      transfer via acupuncture needles by using five metal materials: silver, copper,
      brass, iron, and stainless steel. A silver needle of the type extensively applied
      in acupuncture can dissipate more than seven times as much heat as a stainless
      steel needle of the same type. Heat transfer through such a needle is
      significant, compared to natural body-energy consumption over a range of ambient
      temperatures. The mechanism by which heat flows in or out of the body through the
      needles may be crucial in the remedial efficacy of acupuncture. 

PMID- 25952125
TI  - Analysis of Vacuous Pulse and Replete Pulse Using a Clip-type Pulsimeter Equipped
      with a Hall Sensor.
AB  - A logistic regression equation for the vacuous pulse and the replete pulse was
      determined based on data obtained using a clip-type pulsimeter equipped with a
      Hall device that sensed the change in the magnetic field due to the minute
      movement of a radial artery. To evaluate the efficacy of the two different pulses
      from the deficiency and the excess syndrome groups, we performed a clinical
      trial, and we used a statistical regression analysis to process the clinical data
      from the 180 participants who were enrolled in this study. The ratio of the
      systolic peak's amplitude to its time in the pulse's waveform was found to be a
      major efficacy parameter for differentiating between the vacuous pulse and the
      replete pulse using an empirical equation that was deduced from the data using a
      statistical logistic regression method. This logistic regression equation can be
      applied to develop a novel algorithm for pulse measurements based on Oriental
      medical diagnoses. 

PMID- 25952126
TI  - Acupuncture regulates the heart rate variability.
AB  - Acupuncture is widely used in clinical practice. According to traditional
      acupuncture theory, the Neiguan acupoint (PC6) is one of the most commonly used
      acupoints and is indicated for treating cardiovascular-related disorders. We
      present the case of a 27-year-old female who had been diagnosed with ventricular
      septal defect and had undergone surgery to repair the defect at the age of 11
      years. The patient had no obvious symptoms, such as palpitations and difficulty
      breathing. However, while performing electrocardiography (ECG), we found that she
      suffered from arrhythmia, and therefore, we treated her by acupuncture at the
      left PC6. An ECG monitor was used to record data during the entire acupuncture
      procedure, which was divided into the following three segments: prior to, during,
      and after acupuncture. Various indices of heart rate variability (HRV) were then
      determined and analyzed. The results indicate that acupuncture can regulate the
      HRV effectively; however, more studies are needed to confirm this finding. 

PMID- 25952127
TI  - Empirical versus Etiological Approaches in Oriental Medical Research.
AB  - Although Oriental medicine, by nature, may be considered an etiology-based
      approach to healing, its role in modern research is primarily empirical. The
      absolute dependence on symptomatic presentation to establish acupuncture point
      selection goes against the grain of traditional Oriental methods, which emphasize
      pulse, tongue, and other diagnostic tools to determine the overall biological and
      psychological conditions of the patient. Recently introduced diagnostic methods
      in Oriental medical research indicate a potential shift from empirically to
      etiologically centered designs. This article reviews current mainstream
      approaches to efficacy trial designs and proceeds with the analysis of newer
      research models, such as a constitutional approach spearheaded in Korea by the
      field of four-constitutional medicine. 

PMID- 25952128
TI  - DNA budding of primo microcells.

PMID- 25952129
TI  - Next generation TAVI with the Lotus Valve System: a repositionable and fully
      retrievable transcatheter aortic valve prosthesis.
AB  - Transcatheter aortic valve implantation (TAVI) is the new standard of care for
      selected patients with severe symptomatic aortic stenosis who are at high risk
      for surgical aortic valve replacement (AVR), or are inoperable. Multicentre
      randomised controlled trials have demonstrated equivalent or superior clinical
      outcomes for TAVI compared to AVR in carefully selected patient cohorts. A number
      of important limitations were observed with early generation TAVI valves and
      their delivery systems, and rapid evolution of the technology continues. The
      Lotus Valve System aims to address a number of these limitations - it is
      repositionable and retrievable, and has an adaptive seal to prevent paravalvular
      aortic regurgitation. Early clinical outcomes for the Lotus Valve System have
      recently been published with promising results in terms of paravalvular
      regurgitation and repositionability. 

PMID- 25952130
TI  - Current controversies in PCI pharmacotherapy.
AB  - Coronary artery disease and atherothrombosis are complex pathologic entities. The
      intricate interplay between anatomical, cellular and molecular factors
      characterizes their pathogenesis and determines their clinical manifestations.
      Coronary artery revascularization strategies, by restoring myocardial blood
      perfusion, only partially treat ischemic heart disease in its complexity.
      Pharmacological therapies targeting molecular and cellular components involved in
      the pathophysiology of atherothrombosis are mandatory in order to prevent
      cardiovascular complications during and after revascularization and therefore
      improve clinical outcomes. The developments of antithrombotic pharmacotherapies
      occurred as a result of an improved understanding of the mechanisms underlying
      atherothrombotic disease. Unfortunately, the optimal antithrombotic therapy, in
      both acute and chronic settings, often set significant challenges in daily
      practice. The main objective of optimal antithrombotic therapies, targeting
      coagulation factors or the platelet system, is to maximize the anti-thrombotic
      efficacy while minimizing the bleeding risk. The subtle balance between ischemic
      and bleeding risk is a complex clinical conundrum that involves pharmacologic
      factors, the clinical phenotype of coronary artery disease and patient's clinical
      comorbidities. In a contemporary era, in which a broad armamentarium of
      pharmacologic agents and diagnostic tools are available, physician practice
      should shift toward a progressively more customized patient care. For this
      purpose, selection of the optimal acute and chronic percutaneous coronary
      intervention (PCI) pharmacotherapy, in terms of potency, duration and adherence,
      cannot disregard an individualized and careful evaluation of the patient's
      ischemic and hemorrhagic risk. It is within this context that in the present
      review article we sought to expose the current topics of debate and controversies
      in acute and chronic anticoagulant and antiplatelet therapies in patients
      undergoing PCI. 

PMID- 25952131
TI  - X-ray Photoelectron Spectroscopy of Pyridinium-Based Ionic Liquids: Comparison to
      Imidazolium- and Pyrrolidinium-Based Analogues.
AB  - We investigate eight 1-alkylpyridinium-based ionic liquids of the form [Cn Py][A]
      by using X-ray photoelectron spectroscopy (XPS). The electronic environment of
      each element of the ionic liquids is analyzed. In particular, a reliable fitting
      model is developed for the C 1s region that applies to each of the ionic liquids.
      This model allows the accurate charge correction of binding energies and the
      determination of reliable and reproducible binding energies for each ionic
      liquid. Shake-up/off phenomena are determinedfor both C 1s and N 1s spectra. The
      electronic interaction between cations and anions is investigated for both simple
      ionic liquids and an example of an ionic-liquid mixture; the effect of the anion
      on the electronic environment of the cation is also explored. Throughout the
      study, a detailed comparison is made between [C8 Py][A] and analogues including 1
      octyl-1-methylpyrrolidinium- ([C8 C1 Pyrr][A]), and 1-octyl-3-methylimidazolium-
      ([C8 C1 Im][A]) based samples, where X is common to all ionic liquids. 

PMID- 25952132
TI  - From one generation to the next: a comprehensive account of sympathetic receptor
      control in branching arteriolar trees.
AB  - The effect of the sympathetic nervous system on blood flow distribution within
      skeletal muscle microvasculature is conditional upon regional activation of
      receptors for sympathetic neurotransmitters. Previous studies have shown that
      proximal arterioles are largely governed by adrenergic activation, whereas it is
      speculated that distal branches are controlled by peptidergic and purinergic
      activation. However, no study has systematically evaluated the activation of
      adrenergic, peptidergic and purinergic receptors in continuously branching
      arteriolar trees of an individual skeletal muscle model. Therefore, in the
      present study, sympathetic agonists were used to evaluate the constriction
      responses along first to fifth order arterioles in continuously branching
      arteriolar trees of a in vivo rat gluteus maximus muscle preparation with respect
      to specific activation of receptors for sympathetic neurotransmitters (alpha1R,
      alpha2R, NPY1R and P2X1R). Constriction responses were incorporated into a
      mathematical blood flow model to estimate the total flow, resistance and red
      blood cell flow heterogeneity within a computationally reconstructed gluteus
      maximus arteriolar network. For the first time, the effects of activating
      receptors for sympathetic neurotransmitters on vasoconstrictor responses and the
      ensuing haemodynamics in continuously branching arteriolar trees of skeletal
      muscle were characterized, where proximal arterioles responded most to alpha1R
      and alpha2R adrenergic activation, whereas distal arterioles responded most to
      Y1R and P2X1R activation. Total flow and resistance changed with activation of
      all receptors, whereas red blood cell flow heterogeneity was largely affected by
      peptidergic and purinergic activation in distal arterioles. The reported data
      highlight the functional consequences of topologically-dependent sympathetic
      control and may serve as novel input parameters in computational modelling of
      network flow.

PMID- 25952133
TI  - Transparent conductive graphene textile fibers.
AB  - Transparent and flexible electrodes are widely used on a variety of substrates
      such as plastics and glass. Yet, to date, transparent electrodes on a textile
      substrate have not been explored. The exceptional electrical, mechanical and
      optical properties of monolayer graphene make it highly attractive as a
      transparent electrode for applications in wearable electronics. Here, we report
      the transfer of monolayer graphene, grown by chemical vapor deposition on copper
      foil, to fibers commonly used by the textile industry. The graphene-coated fibers
      have a sheet resistance as low as ~1 kOmega per square, an equivalent value to
      the one obtained by the same transfer process onto a Si substrate, with a
      reduction of only 2.3 per cent in optical transparency while keeping high
      stability under mechanical stress. With this approach, we successfully achieved
      the first example of a textile electrode, flexible and truly embedded in a yarn. 

PMID- 25952135
TI  - Further evidence of DEPDC7 DNA hypomethylation in depression: A study in adult
      twins.
AB  - Late and early stressful factors have widely been recognized to play a role in
      the aetiology of depression. Recent research indicates that such adverse
      environmental stimuli may alter gene expression in humans via epigenetic
      modifications. While epigenetic changes such as DNA methylation are likely
      involved in these processes, it is still unknown what specific genomic loci may
      be hyper- or hypo-methylated in depression. The association between depressive
      symptoms during the last 30 days (Brief Symptom Inventory [BSI]) and peripheral
      blood DNA methylation levels at genomic loci previously reported as
      epigenetically altered in saliva and brain of depressive patients was evaluated
      in a community sample of 34 adult Caucasian MZ twins (17 pairs). Intrapair DNA
      methylation differences in an intron of DEPDC7 (chr11:33040743) were associated
      with intrapair differences in current depressive symptoms. Accordingly, a site
      specific 10% DNA hypomethylation in a co-twin would correlate with a current
      depressive symptom score around 3.1 BSI points above the score of his/her less
      depressed co-twin. These findings indicate that DEPDC7 hypomethylation in
      peripheral blood DNA may be associated with recent depressive symptomatology, in
      line with previous results. 

PMID- 25952136
TI  - P-LORAKS: Low-rank modeling of local k-space neighborhoods with parallel imaging
      data.
AB  - PURPOSE: To propose and evaluate P-LORAKS a new calibrationless parallel imaging
      reconstruction framework. THEORY AND METHODS: LORAKS is a flexible and powerful
      framework that was recently proposed for constrained MRI reconstruction. LORAKS
      was based on the observation that certain matrices constructed from fully sampled
      k-space data should have low rank whenever the image has limited support or
      smooth phase, and made it possible to accurately reconstruct images from
      undersampled or noisy data using low-rank regularization. This paper introduces P
      LORAKS, which extends LORAKS to the context of parallel imaging. This is achieved
      by combining the LORAKS matrices from different channels to yield a larger but
      more parsimonious low-rank matrix model of parallel imaging data. This new model
      can be used to regularize the reconstruction of undersampled parallel imaging
      data, and implicitly imposes phase, support, and parallel imaging constraints
      without needing to calibrate phase, support, or sensitivity profiles. RESULTS:
      The capabilities of P-LORAKS are evaluated with retrospectively undersampled data
      and compared against existing parallel MRI reconstruction methods. Results show
      that P-LORAKS can improve parallel imaging reconstruction quality, and can enable
      the use of new k-space trajectories that are not compatible with existing
      reconstruction methods. CONCLUSION: The P-LORAKS framewok provides a new and
      effective way to regularize parallel imaging reconstruction.

PMID- 25952137
TI  - Complexity and dynamism from an urban health perspective: a rationale for a
      system dynamics approach.
AB  - In a variety of urban health frameworks, cities are conceptualized as complex and
      dynamic yet commonly used epidemiological methods have failed to address this
      complexity and dynamism head on due to their narrow problem definitions and
      linear analytical representations. Scholars from a variety of disciplines have
      also long conceptualized cities as systems, but few have modeled urban health
      issues as problems within a system. Systems thinking in general and system
      dynamics in particular are relatively new approaches in public health, but ones
      that hold immense promise as methodologies to model and analyze the complexity
      underlying urban processes to effectively inform policy actions in dynamic
      environments. This conceptual essay reviews the utility of applying the concepts,
      principles, and methods of systems thinking to the study of complex urban health
      phenomena as a complementary approach to standard epidemiological methods using
      specific examples and provides recommendations on how to better incorporate
      systems thinking methods in urban health research and practice. 

PMID- 25952138
TI  - Thermal properties and morphology changes in degradation process of poly(L
      lactide-co-glycolide) matrices with risperidone.
AB  - Determining thermal properties and morphology seems to be useful in the analysis
      of release and degradation processes form polymeric materials. Risperidone is
      available in the formulation of a long-acting injection based on poly(D,L-lactide
      co-glycolide). Currently, alternative solutions are also offered, i.e., nano- and
      microparticles or implants, including copolymers of lactide and glycolide. The
      effect of risperidone content on the properties of poly(L-lactide-co-glycolide)
      matrices was determined. The study also involved an assessment of the changes
      during degradation. Risperidone free matrices and the matrices with risperidone
      were obtained by solvent casting. Thermal characteristics were tested by means of
      differential scanning calorimetry, and the morphology was evaluated using a
      scanning electron microscope. Risperidone did not change significantly semi
      crystalline structure of poly(L-lactide-co-glycolide) matrices. The decrease in
      crystallization temperature and glass transition temperature during degradation
      was observed. Many pores and their deformation, the widening of pore area, cracks
      and slits because of degradation were observed. The analysis of thermal
      properties and morphology allowed us to explain degradation process. Matrices
      exhibited stable process of degradation, which may be advantageous for
      development of prolonged risperidone release systems. 

PMID- 25952139
TI  - Conformational effects in protein electrospray-ionization mass spectrometry.
AB  - Electrospray-ionization mass spectrometry (ESI-MS) is a key tool of structural
      biology, complementing the information delivered by conventional biochemical and
      biophysical methods. Yet, the mechanism behind the conformational effects in
      protein ESI-MS is an object of debate. Two parameters-solvent-accessible surface
      area (As) and apparent gas-phase basicity (GBapp)-are thought to play a role in
      controlling the extent of protein ionization during ESI-MS experiments. This
      review focuses on recent experimental and theoretical investigations concerning
      the influence of these parameters on ESI-MS results and the structural
      information that can be derived. The available evidence supports a unified model
      for the ionization mechanism of folded and unfolded proteins. These data indicate
      that charge-state distribution (CSD) analysis can provide valuable structural
      information on normally folded, as well as disordered structures.

PMID- 25952140
TI  - Treatment efficacy and safety of canaloplasty for open-angle glaucoma after 5
      years.

PMID- 25952142
TI  - An automated perfusion bioreactor for the streamlined production of engineered
      osteogenic grafts.
AB  - A computer-controlled perfusion bioreactor was developed for the streamlined
      production of engineered osteogenic grafts. This system automated the required
      bioprocesses, from the initial filling of the system through the phases of cell
      seeding and prolonged cell/tissue culture. Flow through chemo-optic micro-sensors
      allowed to non-invasively monitor the levels of oxygen and pH in the perfused
      culture medium throughout the culture period. To validate its performance,
      freshly isolated ovine bone marrow stromal cells were directly seeded on porous
      scaffold granules (hydroxyapatite/beta-tricalcium-phosphate/poly-lactic acid),
      bypassing the phase of monolayer cell expansion in flasks. Either 10 or 20 days
      after culture, engineered cell-granule grafts were implanted in an ectopic mouse
      model to quantify new bone formation. After four weeks of implantation,
      histomorphometry showed more bone in bioreactor-generated grafts than cell-free
      granule controls, while bone formation did not show significant differences
      between 10 days and 20 days of incubation. The implanted granules without cells
      had no bone formation. This novel perfusion bioreactor has revealed the
      capability of activation larger viable bone graft material, even after shorter
      incubation time of graft material. This study has demonstrated the feasibility of
      engineering osteogenic grafts in an automated bioreactor system, laying the
      foundation for a safe, regulatory-compliant, and cost-effective manufacturing
      process.

PMID- 25952141
TI  - IM30 triggers membrane fusion in cyanobacteria and chloroplasts.
AB  - The thylakoid membrane of chloroplasts and cyanobacteria is a unique internal
      membrane system harbouring the complexes of the photosynthetic electron transfer
      chain. Despite their apparent importance, little is known about the biogenesis
      and maintenance of thylakoid membranes. Although membrane fusion events are
      essential for the formation of thylakoid membranes, proteins involved in membrane
      fusion have yet to be identified in photosynthetic cells or organelles. Here we
      show that IM30, a conserved chloroplast and cyanobacterial protein of
      approximately 30 kDa binds as an oligomeric ring in a well-defined geometry
      specifically to membranes containing anionic lipids. Triggered by Mg(2+),
      membrane binding causes destabilization and eventually results in membrane
      fusion. We propose that IM30 establishes contacts between internal membrane sites
      and promotes fusion to enable regulated exchange of proteins and/or lipids in
      cyanobacteria and chloroplasts. 

PMID- 25952143
TI  - Suicide Risk Assessment and Management in Practice: The Quintessential Clinical
      Activity.

PMID- 25952144
TI  - This Is Water Revisited: Creativity Lost.

PMID- 25952145
TI  - Test of visuospatial construction: Validity evidence in extremely low birth
      weight and late preterm children at early school age.
AB  - The Test of Visuospatial Construction (TVSC), a measure of visuoconstruction that
      does not rely on upper extremity motor response or written production, was
      administered to extremely low birth weight (ELBW), late preterm (LPT), and term
      participants at preschool (n = 355) and kindergarten (n = 265) ages. TVSC showed
      statistically significant weak-to-moderate positive correlations (age 3: r = .118
      .303; age 6: r = .138-.348) with Developmental VMI, Differential Ability Scales
      II Copying, Matrices, and Pattern Construction subtests, Baron-Hopkins Board
      Test, and the Purdue Pegboard. One-way ANOVA indicated ELBW performed worse than
      Term (p = .044) on visuospatial construction at age 3 with a small-to-medium
      effect size (d = -0.43). No other statistically significant differences were
      found at age 3 on the TVSC (ELBW/LPT: p = .608, d = -0.17; LPT/Term: p = .116, d
      = -0.31). At age 6, ELBW participants performed worse than LPT participants (p =
      .027) and Term participants (p = .012); LPT participants did not differ from Term
      participants. Small effect sizes at age 3 (ELBW < LPT, d = -0.17; ELBW < Term, d
      = -0.43) were notably larger at age 6 (ELBW < LPT, d = -0.42; ELBW < Term, d = 
      0.53). Important practical differences showing LPT participants performed below
      Term participants (d = -0.31) at age 3 were no longer evident at age 6 (d = 
      0.097). These findings provide preliminary evidence of TVSC validity supporting
      its use to detect neuropsychological impairment and to recommend appropriate
      interventions in young preterm children. 

PMID- 25952146
TI  - Endothelial sphingosine kinase/SPNS2 axis is critical for vessel-like formation
      by human mesoangioblasts.
AB  - The interaction between endothelial cells and pericytes is crucial for the
      stabilization of newly formed vessels in angiogenesis. The comprehension of the
      mechanisms regulating pericyte recruitment might open therapeutical perspectives
      on vascular-related pathologies. Sphingosine 1-phosphate (S1P) is a bioactive
      sphingolipid that derives from sphingomyelin catabolism and regulates biological
      functions in cell survival, proliferation, and differentiation. In this study, we
      aimed to identify the role of S1P axis in the intercellular communication between
      human mesenchymal progenitor mesoangioblasts (MAB) and endothelial cells (human
      microvascular endothelial cells (H-MVEC)) in the formation of capillary-like
      structures. We demonstrated that the S1P biosynthetic pathway brought about by
      sphingosine kinases (SK) SK1 and SK2 as well as spinster homolog 2 (SPNS2)
      transporter in H-MVEC is crucial for MAB migration measured by Boyden chambers
      and for the formation and stabilization of capillary-like structures in a 3D
      Matrigel culture. Moreover, the conditioned medium (CM) harvested from H-MVEC,
      where SK1, SK2, and SPNS2 were down-regulated, exerted a significantly diminished
      effect on MAB capillary morphogenesis and migration. Notably, we demonstrated
      that S1P1 and S1P3 receptors were positively involved in CM-induced capillary
      like formation and migration, while S1P2 exerted a negative role on CM-induced
      migratory action of MAB. Finally, SK inhibition as well as MAB S1P1 and S1P3 down
      regulation impaired H-MVEC-MAB cross-talk significantly reducing in vivo
      angiogenesis evaluated by Matrigel plug assay. These findings individuate novel
      targets for the employment of MAB in vascular-related pathologic conditions. KEY
      MESSAGE: * Down-regulation of SK1/2 in H-MVEC impaired vessel formation when
      cultured with MAB. * H-MVEC SPNS2 is critical for morphogenesis and migration
      induced by H-MVEC CM of MAB. * CM from SK1- and SK2-siRNA H-MVEC impaired
      morphogenesis and migration of MAB. * S1P1/3 were involved on CM-induced
      morphogenesis and migration of MAB. * Matrigel plug assay showed the role of S1P
      axis in MAB-endothelial cell interaction.

PMID- 25952147
TI  - Fitting homocysteine to disease models, as well as adjusting the models to the
      disease.

PMID- 25952148
TI  - Current controlled vocabularies are insufficient to uniquely map molecular
      entities to mass spectrometry signal.
AB  - BACKGROUND: The comparison of analyte mass spectrometry precursor (MS1) signal is
      central to many proteomic (and other -omic) workflows. Standard vocabularies for
      mass spectrometry exist and provide good coverage for most experimental
      applications yet are insufficient for concise and unambiguous description of data
      concepts spanning the range of signal provenance from a molecular perspective
      (e.g. from charged peptides down to fine isotopes). Without a standard
      unambiguous nomenclature, literature searches, algorithm reproducibility and
      algorithm evaluation for MS-omics data processing are nearly impossible. RESULTS:
      We show how terms from current official ontologies are too vague or ambiguous to
      explicitly map molecular entities to MS signals and we illustrate the
      inconsistency and ambiguity of current colloquially used terms. We also propose a
      set of terms for MS1 signal that uniquely, succinctly and intuitively describe
      data concepts spanning the range of signal provenance from full molecule downs to
      fine isotopes. We suggest that additional community discussion of these terms
      should precede any further standardization efforts. We propose a novel
      nomenclature that spans the range of the required granularity to describe MS data
      processing from the perspective of the molecular provenance of the MS signal.
      CONCLUSIONS: The proposed nomenclature provides a chain of succinct and unique
      terms spanning the signal created by a charged molecule down through each of its
      constituent subsignals. We suggest that additional community discussion of these
      terms should precede any further standardization efforts.

PMID- 25952150
TI  - Electrocatalytic activity of alkyne-functionalized AgAu alloy nanoparticles for
      oxygen reduction in alkaline media.
AB  - 1-Dodecyne-functionalized AgAu alloy nanoparticles were synthesized by chemical
      reduction of metal salt precursors at varied initial feed ratios. Transmission
      electron microscopic measurements showed that the nanoparticles were all rather
      well dispersed with the average core diameter in the narrow range of 3 to 5 nm. X
      ray photoelectron spectroscopic studies confirmed the formation of AgAu alloy
      nanoparticles with the gold concentration ranging from approximately 25 at% to 55
      at%. Consistent results were obtained in UV-vis spectroscopic measurements where
      the nanoparticle surface plasmon resonance red-shifted almost linearly with
      increasing gold concentrations. The self-assembly of 1-dodecyne ligands on the
      nanoparticle surface was manifested in infrared spectroscopic measurements.
      Importantly, the resulting nanoparticles exhibited apparent electrocatalytic
      activity for oxygen reduction in alkaline media, and the performance was found to
      show a volcano variation in the Au content in the alloy nanoparticles, with the
      best performance observed for the samples with ca. 35.5 at% Au. The enhanced
      catalytic activity, as compared to pure Ag nanoparticles or even commercial Pt/C
      catalysts, was accounted for by the unique metal-ligand interfacial bonding
      interactions as well as alloying effects that increased metal-oxygen affinity. 

PMID- 25952149
TI  - Hereditary angioedema with normal C1-INH with versus without specific F12 gene
      mutations.
AB  - BACKGROUND: Hereditary angioedema with normal C1-INH may be linked to specific
      mutations in the coagulation factor 12 (FXII) gene (HAE-FXII) or mutations in
      genes that are still unknown (HAE-unknown). To assess the differences in
      transmission and inheritance, clinical features, and laboratory parameters
      between patients with HAE-FXII and HAE-unknown. METHODS: Sixty-nine patients with
      HAE-FXII from 23 unrelated families and 196 patients with HAE-unknown from 65
      unrelated families were studied. RESULTS: Both HAE-FXII and HAE-unknown are
      inherited as autosomal-dominant traits with incomplete penetrance. The male to
      female ratio was 1 : 68 in HAE-FXII and 1 : 6.3 in HAE-unknown. The maternal to
      paternal transmission ratio was 35 : 14 for HAE-FXII and 109 : 12 for HAE
      unknown. Mean age at onset of clinical symptoms was 20.3 years in patients with
      HAE-FXII and 29.6 years in patients with HAE-unknown. The incidence of
      asphyxiation due to angioedema was similar for HAE-FXII and HAE-unknown. Oral
      contraceptives and pregnancies had a significantly higher impact on HAE-FXII than
      on HAE-unknown. Slightly decreased C1-INH activity and C4 concentration were
      observed in more patients with HAE-FXII than HAE-unknown. Tests for FXI and FXII
      activity, plasminogen activator inhibitor 1, and activated partial thromboplastin
      time showed variability but no significant differences between the groups. No
      abnormalities were found for C1-INH protein, C1q, alpha2-macroglobulin,
      antithrombin III, and angiotensin-converting enzyme. In families with HAE-FXII,
      the number of female offspring with F12 mutations was significantly increased and
      that of male offspring was significantly decreased. CONCLUSIONS: HAE-FXII and HAE
      unknown differ in various respects, including gender distribution, genetics,
      symptoms, and estrogen impact.

PMID- 25952151
TI  - Osteogenic differentiation of human MSCs: Specific occupancy of the mitochondrial
      DNA by NFATc1 transcription factor.
AB  - A substantial body of evidence indicates that mitochondrial morphology and
      function change during osteogenic differentiation. However, molecular mechanisms
      linking mitochondrial dynamics with the regulation of osteoblast functions are
      poorly understood. Amongst the molecules that influence the decision of human
      mesenchymal stem cells (hMSCs) to become osteoblasts are Slug and NFATc1
      transcription factors (TFs). These molecules also interfere with different
      mitochondria-dependent pathways in response to a variety of cellular demands. The
      present study investigated the recruitment of Slug and NFATc1 at the D-loop
      regulatory region of mitochondrial DNA (mtDNA) in osteogenic differentiated hMSCs
      with the aim of exploring whether Slug and NFATc1 also act as mitoTFs in the
      mitochondrial pool of nuclear TFs. The results demonstrate that NFATc1, but not
      Slug, is localized in the mitochondria. Using chromatin immunoprecipitation
      assay, we found that NFATc1 is recruited at mtDNA, but this occurs only when the
      calcification process is at its highest in osteo-induced MSC and the maximum
      level of differentiation is reached. Occupancy of the mtDNA by NFATc1 is
      associated with a decreased expression of crucial mitochondrial genes such as
      Cytochrome B and NADH dehydrogenase 1. This suggests that NFATc1 acts as a
      negative regulator of mtDNA transcription during the calcification process and
      interruption of aerobic energy demand. The finding of NFATc1 participation in
      osteogenic differentiation through its direct involvement in the regulatory
      machinery of mitochondria suggests a new role for this TF and adds information on
      communication between mitochondrial and nuclear genomes. 

PMID- 25952152
TI  - Synthesis of a phosphapyracene via metal-mediated cyclization: structural and
      reactivity effects of acenaphthene precursors.
AB  - Metal-mediated synthesis of a new heterocycle, 1-phenyl-phosphapyracene (Ph-4, Ph
      PyraPhos), by tandem phosphination/cyclization of peri-substituted 5-bromo-6
      chloromethylacenaphthene (3) was investigated for comparison to Pt-catalyzed
      formation of 1-phosphaacenaphthenes (2, AcePhos) from the analogous naphthalene
      precursor (1). Reaction of PH2Ph with , NaOSiMe3 and a Cu catalyst gave ; a Pt
      catalyst yielded PHPh(CH2Ar) (Ph-11, Ar = 5-Br-acenaphthyl). Deprotonation of a
      complex of this secondary phosphine, [Pt((R,R)-Me-DuPhos)(Ph)(PHPh(CH2Ar))][PF6]
      (17), generated the phosphido intermediate Pt((R,R)-Me-DuPhos)(Ph)(PPhCH2Ar) (Ph
      8), which cyclized to give [Pt((R,R)-Me-DuPhos)(Ph)(Ph-PyraPhos)][PF6] (18).
      Treatment of P-8 with silver triflate gave 18 and the cyclometalated phosphine
      complex [Pt((R,R)-Me-DuPhos)(kappa(2)-(P,C)-5-Ph2PCH2-6-C12H8)][PF6] (21), which
      might form via Pt(iv) intermediates. The effects of the added "ace" bridge on
      structure and reactivity are discussed.

PMID- 25952153
TI  - Deltamethrin toxicological profile of peridomestic Triatoma sordida in the North
      of Minas Gerais, Brazil.
AB  - BACKGROUND: In general, there was a large reduction in the occurrence of cases of
      Chagas disease in the last decades in Brazil. However, despite all of these
      efforts, there have been various reports of persistent reinfestations of T.
      sordida in a large part of the state of Minas Gerais, for reasons still little
      investigated. Thus, this purpose of this study was to characterize the
      deltamethrin susceptibility profile of peridomestic T. sordida populations from
      North of Minas Gerais-Brazil. METHODS: Susceptibility to deltamethrin was
      assessed in seventeen peridomestic populations of T. sordida from North region of
      Minas Gerais, Brazil. Serial dilutions of deltamethrin in acetone (0.2 MUL) were
      topically applied in first instar nymphs (F1, five days old, fasting, weight 1.2
      +/- 0.2 mg). Dose response results were analyzed with POLO program, determining
      the lethal doses, slope and resistance ratios (RR). RESULTS: Susceptibility
      profile characterization of T. sordida populations revealed resistance ratios
      (RR50) ranging from 2.50 to 7.08. CONCLUSIONS: In fact, we know very little about
      the real impact of the resistance ratios obtained in the laboratory bioassays on
      the effectiveness of the vector control activities in the field. Thus, we prefer
      to refer to the populations with RR > 5 as populations with altered
      susceptibility. For these populations, the realization of laboratory and field
      trials, simultaneous and complementary, permitting the evaluation of both, is
      recommended.

PMID- 25952154
TI  - Modulation of transepithelial electric resistance (TEER) in reconstructed human
      epidermis by excipients known to permeate intestinal tight junctions.
AB  - Several excipients are commonly used to enhance the drug absorption through
      simple epithelia of the digestive tract. They permeate the paracellular barrier
      constituted by tight junctions (TJs). We compared the effects of two excipients,
      sodium caprate (C10) and a self-emulsifying excipient Labrasol composed of a
      mixture of caprylocaproyl polyoxyl-8 glycerides, both applied to emerged
      reconstructed human epidermis either 'systemically', that is by addition to the
      culture medium, or topically. During the 'systemic' application, which produced
      cytoplasmic translocation of occludin and leakage of the biotin marker into the
      lower stratum corneum, the decrease in the trans-epithelial electrical resistance
      (TEER) was less abrupt with Labrasol when compared with C10, even though both
      excipients produced comparable final effects over time. With topical Labrasol, a
      significant TEER decrease was obtained with 5 times the 'systemic'
      concentrations. Topical application of C10 also resulted in the loss of the
      barrier function measured with TEER but had dramatic deleterious effects on the
      tissue morphology observed with light and electron microscopy. Our study
      demonstrates the potential value of Labrasol as an enhancer of bioavailability of
      molecules applied through the transcutaneous route. Our results suggest
      modulation of the epidermal TJs by both compounds. Even though the C10 action was
      at least partly due to overall cell damage and despite the fact that the decrease
      in TEER after topical application was apparently related to the permeabilization
      of the primary barrier of the stratum corneum in the first place. 

PMID- 25952155
TI  - Multispectral imaging reveals the tissue distribution of tetraspanins in human
      lymphoid organs.
AB  - Multispectral imaging is a novel microscopy technique that combines imaging with
      spectroscopy to obtain both quantitative expression data and tissue distribution
      of different cellular markers. Tetraspanins CD37 and CD53 are four-transmembrane
      proteins involved in cellular and humoral immune responses. However,
      comprehensive immunohistochemical analyses of CD37 and CD53 in human lymphoid
      organs have not been performed so far. We investigated CD37 and CD53 protein
      expression on primary human immune cell subsets in blood and in primary and
      secondary lymphoid organs. Both tetraspanins were prominently expressed on
      antigen-presenting cells, with highest expression of CD37 on B lymphocytes.
      Analysis of subcellular distribution showed presence of both tetraspanins on the
      plasma membrane and on endosomes. In addition, CD53 was also present on
      lysosomes. Quantitative analysis of expression and localization of CD37 and CD53
      on lymphocytes within lymphoid tissues by multispectral imaging revealed high
      expression of both tetraspanins on CD20(+) cells in B cell follicles in human
      spleen and appendix. CD3(+) T cells within splenic T cell zones expressed lower
      levels of CD37 and CD53 compared to T cells in the red pulp of human spleen. B
      cells in human bone marrow highly expressed CD37, whereas the expression of CD53
      was low. In conclusion, we demonstrate differential expression of CD37 and CD53
      on primary human immune cells, their subcellular localization and their
      quantitative distribution in human lymphoid organs. This study provides a solid
      basis for better insight into the function of tetraspanins in the human immune
      response. 

PMID- 25952156
TI  - Chaperone molecules concentrate together with the ubiquitin-proteasome system
      inside particulate cytoplasmic structures: possible role in metabolism of
      misfolded proteins.
AB  - Ubiquitin-proteasome system (UPS) proteins and proteolytic activity are localized
      in a recently identified cytoplasmic structure characterized by accumulation of
      barrel-like particles, which is known as the particulate cytoplasmic structure
      (PaCS). PaCSs have been detected in neoplastic, preneoplastic, chronically
      infected, and fetal cells, which produce high amounts of misfolded proteins to be
      degraded by the UPS. Chaperone molecules are crucial in the early stages of
      handling misfolded proteins; therefore, we searched for these molecules in PaCSs.
      Heat shock proteins (Hsp), Hsp90, Hsp70, Hsp40, and Bcl-2-associated athanogene
      (Bag)3 chaperones, although not Bag6, were selectively concentrated into PaCSs of
      several cell lines and ex vivo fetal or neoplastic cells. Present findings point
      to PaCSs as an integrated, active UPS center well equipped for metabolism of
      misfolded proteins, especially in cells under physiological (fetal development)
      or pathological (neoplasia or inflammation) stress. 

PMID- 25952157
TI  - Selective localization of diacylglycerol kinase (DGK)zeta in the terminal tubule
      cells in the submandibular glands of early postnatal mice.
AB  - The present immunohistochemical study was attempted to localize in the
      submandibular glands of mice at various postnatal stages a diacylglycerol kinase
      (DGK) isoform termed DGKzeta which is characterized by a nuclear localization
      signal and a nuclear export signal. This attempt was based on following facts:
      the continuous postnatal differentiation of glandular cells in the rodent
      submandibular gland, the regulatory role of DGK in the activity of protein kinase
      C (PKC) through attenuation of diacylglycerol (DAG), and the possible involvement
      of PKC in various cellular activities including the saliva secretion as well as
      the cell differentiation. As a result, a selective localization of
      immunoreactivity for DGKzeta was detected in terminal tubule (TT) cells which
      comprise a majority of the newborn acinar structure and differentiate into the
      intercalated duct cells and/or the acinar cells. The immunoreactivity was
      deposited in portions of the cytoplasm lateral and basal to the nucleus, but not
      in the nuclei themselves. Although the immunoreactive TT cells remained until
      later stages in female specimen than in male, they eventually disappeared in both
      sexes by young adult stages. The present finding suggests that the regulatory
      involvement of DGKzeta in PKC functions via control of DAG is exerted in the
      differentiation of the TT cells. In addition, another possible involvement of
      DGKzeta in the regulation of secretion of the TT cells as well as its functional
      significance of its nuclear localization in the submandibular ganglion cells was
      also discussed. 

PMID- 25952158
TI  - "If you can have one glass of wine now and then, why are you denying that to a
      woman with no evidence": Knowledge and practices of health professionals
      concerning alcohol consumption during pregnancy.
AB  - BACKGROUND: Alcohol consumption during pregnancy has the potential to cause
      significant harm to the foetus and the current Australian guidelines state that
      it is safest not to drink alcohol while pregnant. However, conflicting messages
      often appear in the media and it is unclear if the message to avoid alcohol is
      being effectively conveyed to pregnant women. AIMS: This research aims to explore
      the advice that health professionals provide to pregnant women about alcohol
      consumption; the knowledge of health professionals regarding the effects of
      alcohol consumption; and their consistency with following the Australian
      guidelines. METHODS: Ten semi-structured face to face interviews were conducted
      with health professionals who regularly provide antenatal care. These include
      midwives, obstetricians, and shared care general practitioners. A six-stage
      thematic analysis framework was used to analyse the interview data in a
      systematic way to ensure rigour and transparency. The analysis involved coding
      data extracts, followed by identifying the major themes. FINDINGS: Health
      professionals displayed adequate knowledge that alcohol can cause physical and
      mental difficulties that are lifelong; however, knowledge of the term FASD and
      the broad spectrum of difficulties associated with alcohol consumption during
      pregnancy was limited. Although health professionals were willing to discuss
      alcohol with pregnant women, many did not make this a routine part of practice,
      and several concerning judgements were noted. CONCLUSION: Communication between
      health professionals and pregnant women needs to be improved to ensure that
      accurate information about alcohol use in pregnancy is being provided. Further,
      it is important to ensure that the national guidelines are being supported by
      health professionals.

PMID- 25952159
TI  - Clinical diagnosis of pelvic endometriosis: a scoping review.
AB  - BACKGROUND: Accurate and timely diagnosis of endometriosis is associated with
      confusion. Clinical manifestations, imaging techniques, biomarkers and surgical
      techniques are used as diagnostic approaches. This paper reviews current evidence
      on clinical manifestation in order to help practitioners and perhaps improve
      women's health. METHODS: A review of the literature on clinical diagnosis of
      pelvic endometriosis that appeared in the English language biomedical journals
      was performed using PubMed, Science Direct and Google Scholar. The search
      strategy included the combination of key words 'endometriosis' and 'diagnosis' or
      'clinical diagnosis' in the titles or abstracts of articles. The search included
      all papers published during the year 2000 to 2014. Then, the findings were
      classified in order to summarize the evidence. RESULTS: Using the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, in
      all 51 papers were found relevant and included in this review. In general we
      found three categories of diagnostic approaches for clinical manifestation
      including: i) diagnosis via symptoms obtained from history taking, ii) diagnosis
      via signs obtained from physical examination and iii) diagnosis via risk factors
      obtained from history taking. CONCLUSION: Diagnosis of endometriosis is a matter
      of concern. Since the disease is associated with diverse clinical symptoms and
      signs, deeper and more comprehensive consideration according to patient's history
      and clinical findings is recommended for early and more accurate detection in
      order to prioritize women for further investigation and contribute to its early
      management.

PMID- 25952161
TI  - Ultrasonographic Visualization of Accessory Hepatic Veins and Their Lesions in
      Budd-Chiari Syndrome.
AB  - The aim of this study was to investigate the ultrasonographic features of
      accessory hepatic veins (AHVs) and their lesions in Budd-Chiari syndrome (BCS).
      Three hundred patients with BCS were examined by ultrasonography with
      multifrequency (3-6 MHz) convex transducers. Sonography was performed 1 to 2 wk
      before digital subtraction angiography and computed tomography angiography or
      magnetic resonance imaging. Using sonograms, we evaluated the number, course,
      diameter, orifice, lesions and hemodynamics of patent and obstructed AHVs.
      Ultrasonography was superior to digital subtraction angiography, computed
      tomography angiography and magnetic resonance imaging in revealing AHV lesions
      and hemodynamics. Dilated AHVs were detected in 227 patients. There were 239
      caudate lobe veins in 167 patients and 168 inferior right hepatic veins in 151
      patients. Both caudate lobe veins and inferior right hepatic veins were found in
      91 of the 227 patients. The inlets to AHVs were located mainly on the right
      lateral or right anterior wall of the inferior vena cava, and the remnant, on the
      left lateral wall. AHV lesions comprised mainly septal obstruction and segmental
      stenosis. The hemodynamics of AHVs varied with the condition of inferior vena
      cava and AHVs. Ultrasonic examination can reveal AHVs and their lesions in
      patients with BCS and is helpful in choosing and planning therapeutic approaches.

PMID- 25952160
TI  - Improving dietary quality in youth with type 1 diabetes: randomized clinical
      trial of a family-based behavioral intervention.
AB  - BACKGROUND: Diets of children with type 1 diabetes are low in fruits, vegetables,
      and whole grains, and high in foods of minimal nutritional value, increasing risk
      for future adverse health outcomes. This 18-month randomized clinical trial
      tested the effect of a family-based behavioral intervention integrating
      motivational interviewing, active learning, and applied problem-solving on the
      primary outcomes of dietary intake and glycemic control among youth with type 1
      diabetes. METHODS: A parallel-group study with equal randomization was conducted
      at an outpatient, free-standing, multidisciplinary tertiary diabetes center in
      the United States. Eligible youth were those age 8-16 years with type 1 diabetes
      diagnosis >=1 year and hemoglobin A1c (HbA1c) >=6.5% and <=10.0%. Participants
      were 136 parent-youth dyads (treatment n = 66, control n = 70). The intervention
      consisted of 9 in-clinic sessions delivered to the child and parent; control
      condition comprised equivalent assessments and number of contacts without dietary
      advice. Dietary intake was assessed using 3-day diet records at 6 time points
      across the 18-month study. Dietary outcomes included the Healthy Eating Index
      2005 (HEI2005; index measuring conformance to the 2005 United States Dietary
      Guidelines for Americans) and Whole Plant Food Density (WPFD; number of cup or
      ounce equivalents per 1000 kcal of whole grains, whole fruit, vegetables,
      legumes, nuts, and seeds consumed). HbA1c was obtained every 3 months. Overall
      comparison of outcome variables between intervention and usual care groups was
      conducted using permutation tests. RESULTS: There was a positive intervention
      effect across the study duration for HEI2005 (p = .015) and WPFD (p = .004). At
      18 months, HEI2005 was 7.2 greater (mean +/- SE 64.6 +/- 2.0 versus 57.4 +/-
      1.6), and WPFD was 0.5 greater (2.2 +/- 0.1 versus 1.7 +/- 0.1) in the
      intervention group versus control. There was no difference between groups in
      HbA1c across the study duration. CONCLUSIONS: This behavioral nutrition
      intervention improved dietary quality among youth with type 1 diabetes, but did
      not impact glycemic control. Findings indicate the potential utility of
      incorporating such strategies into clinical care, and suggest that improvement in
      diet quality can be achieved in families living with this burdensome disease.
      TRIAL REGISTRATION: Clinicaltrials.gov registration number: NCT00999375.

PMID- 25952162
TI  - Adding Ultrasound to the Evaluation of Patients with Pathologic Nipple Discharge
      to Diagnose Additional Breast Cancers: Preliminary Data.
AB  - The aim of this study was to assess the malignancy yield of ultrasound Breast
      Imaging Reporting and Data System (BI-RADS) classification and the diagnostic
      value of adding ultrasound to diagnosis of breast cancer in patients with
      pathologic nipple discharge. Of 267 patients with pathologic nipple discharge
      seen from February 2003 to March 2011, 198 with histopathologic confirmation and
      follow-up data were included. Ultrasound images and mammograms were analyzed
      according to BI-RADS. The malignancy rate for each BI-RADS category and the
      difference in diagnostic performance resulting from the addition of ultrasound to
      mammography were calculated. Of the 198 enrolled patients, 34 were diagnosed with
      a malignancy. The malignancy rates obtained with the addition of ultrasound to
      mammography were 0.0% (0 of 27) for category 1, 5.9% (1/17) for category 2, 9.4%
      (5/53) for category 3, 21.5% (20/93) for category 4 and 100% (8/8) for category
      5. The malignancy rates for mammography alone were 7.7%-9.0% for categories 1-3,
      68.5% (13/19) for category 4 and 100.0% (5/5) for category 5. Adding US to
      mammography did not significantly increase sensitivity compared with mammography
      alone. Other diagnostic performance markers such as specificity and positive
      predictive value were not improved. Among patients for whom mammograms were
      available, ultrasound detected 5 breast cancers (26.3%) in addition to the 19
      breast cancers found by positive mammography. Although it did not increase
      overall diagnostic performance in patients with pathologic nipple discharge,
      addition of ultrasound to mammography did detect an additional 26.3% of malignant
      lesions. 

PMID- 25952163
TI  - Direct synthesis of pyrazoles from esters using tert-butoxide-assisted C-(C=O)
      coupling.
AB  - This paper describes the direct synthesis of pyrazoles from esters that comprises
      two sequential reactions: tert-butoxide-assisted C-C(=O) coupling reaction to
      yield beta-ketonitrile or alpha,beta-alkynone intermediates, and condensation by
      hydrazine addition. The method reported allows for easy control of the
      regioselectivity and structure of substituents at N-1, C-3, C-4 and/or C-5
      positions.

PMID- 25952164
TI  - Paper on food banks does not justify a link to party politics.

PMID- 25952165
TI  - Biodegradation and bioresorption of poly(E-caprolactone) nanocomposite scaffolds.
AB  - A new type of hybrid three-dimensional scaffolds was prepared using poly(E
      caprolactone) (PCL) and chitosan-modified montmorillonite by solvent casting and
      particulate leaching method. The scaffolds were characterized by scanning
      electron microscopy coupled with energy dispersive spectroscopy (EDS), X-ray
      diffraction (XRD), and dynamic mechanical analysis to study the structural and
      mechanical properties. The resulting scaffolds displayed high porosity with
      highly interconnected pores. EDS analysis confirmed the elemental composition of
      the scaffolds. The phase composition of the scaffolds was shown by XRD, which
      also indicated a decrease in crystallinity with the introduction of nanoclay.
      Biodegradability studies which were conducted in simulated physiological
      conditions over a period of four weeks revealed that the PCL-based scaffolds
      degraded by hydrolysis at a slow rate. The overall bioresorbability was also
      slow, with the composite-based scaffolds recording a faster rate than the neat
      polymer-based scaffold. 

PMID- 25952166
TI  - Clinical correlation between a point-of-care testing system and laboratory
      automation for lipid profile.
AB  - BACKGROUND: We evaluated the clinical correlation between the CardioChek PA
      analyzer and a clinical laboratory reference method to use for screening program
      purposes. METHODS: Fasting blood samples were collected on 516 patients (age 20
      85 y). One venous sample was collected using a serum tube for the evaluation on a
      COBAS reference analyzer. A second venous sample was collected in a lithium
      heparin tube and was evaluated on the CardioChek PA analyzer (CCPA venous). A
      fingerstick sample (CCPA fingerstick) was evaluated only on the CardioChek PA
      analyzer. Linear regression analyses were performed for each measured analyte,
      total cholesterol, HDL-cholesterol and triglycerides. RESULTS: The correlation
      between the CCPA fingerstick and CCPA venous was extremely high for HDL-C and
      triglycerides, and good for total cholesterol. Our results demonstrated a good
      clinical agreement for total cholesterol, HDL-C and triglycerides between 97.7%
      and 94.6% in the comparison of the CCPA to the reference analyzer. CONCLUSIONS:
      We identified the pre-analytic phase as an important step to guarantee the
      quality of results and indicate that the CardioChek PA is a reliable lipid point
      of-care testing system that can be used for the application of clinical screening
      anywhere.

PMID- 25952167
TI  - Frequencies and prescription patterns of traditional Chinese medicine use among
      elderly patients in Taiwan: A population-based study.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM), one of the
      most commonly used complementary and alternative medicines, has been receiving
      increasing attention among elderly patients. However, epidemiological reports and
      prescription patterns of geriatric TCM users are few. The aim of this study is to
      use data from a nationwide cohort database to analyze TCM use by the geriatric
      population in Taiwan from 2005 to 2009. MATERIALS AND METHODS: TCM outpatient
      claims data was obtained from the Taiwan National Health Insurance database. Data
      for elderly patients aged 65 years and older were included in the analysis during
      the study period. The demographic data, disease distributions, and frequencies
      and prescription patterns of TCM use by the geriatric population were analyzed.
      RESULTS: The geriatric cohort included 97,210 patients, in which 46,883 patients
      (48%) had used TCM at least once, with a total of 723,478 TCM outpatient visits.
      Of these, 175,857 visits (24.3%) were prompted by "diseases of the
      musculoskeletal system and connective tissue"; more than half of patients with
      such diseases were treated using acupuncture and traumatology manipulative
      therapies. Overall, among the 552,835 visits during which Chinese herbal products
      (CHP) were prescribed, Shu-Jing-Huo-Xie-Tang and Dan Shen (Radix Salvia
      Miltiorrhizae) were the most frequently prescribed herbal formula and single
      herb, respectively, for elderly patients. In addition, Shu-Jing-Huo-Xie-Tang was
      also the most prescribed herbal formula for the most common disease categories of
      "diseases of the musculoskeletal system and connective tissue" among TCM elderly
      patients, followed by Du-Huo-Ji-Sheng-Tang, and Shao-Yao-Gan-Cao-Tang.
      CONCLUSION: This study elucidated the TCM utilization patterns of the geriatric
      population. However, additional studies are warranted to determine the safety and
      efficacy of these CHPs for use by elderly patients in further clinical trials.

PMID- 25952168
TI  - Quantitative ethnobotanical survey of medicinal flora thriving in Malakand Pass
      Hills, Khyber Pakhtunkhwa, Pakistan.
AB  - STUDY OBJECTIVE: Ethnobotanical knowledge is proving to be invaluable for drug
      discovery in the wake of effective prospecting from biodiversity. On the other
      hand, the escalating human pressure is threatening the endogenous flora. Situated
      at the foothill of the Himalayas, Pakistan boasts of rich floristic distribution.
      However, many lush yet imperiled regions of this country has never been explored.
      It inspired us to evaluate and document the taxonomic composition, significance
      of medicinal plants and associated traditional knowledge in the District of
      Malakand, Khyber Pakhtunkhwa Province. MATERIALS AND METHODS: Vegetation growing
      in Malakand pass hills, Pakistan was studied and data were collected using an
      open-ended questionnaire, in addition to interviewing the local elderly,
      knowledgeable persons, and herbal practitioners. Relative Frequency Citation
      (RFC) and Use Value (UV) of the medicinal plants were calculated and their
      correlation was determined by Pearson correlation coefficient. RESULTS: This
      study encompasses 92 plant species belonging to 56 families thriving in the study
      area. The information gathered includes ethnobotanical inventory and their
      pharmacological uses. Quantitative analysis throws light on the consistence of
      RFC and UV. Asteraceae and Lamiaceae were the most abundant families represented
      by 6 species each. Shoots were the most used parts (23.6%) and wound healing
      (7.91%) was the most common therapeutic use. CONCLUSION: The result obtained from
      the study implies that local inhabitants rely on these plants for their medicinal
      requirements. Also, the statistics reveal that, the vegetation can be assessed
      for potential drug leads. However, urban expansion is threatening the existence
      of indigenous flora and old generation with ancient herbal wisdom is perishing.
      So, it appears imperative to preserve the traditional knowledge. This survey is
      expected to contribute to the discovery of novel bioactive constituents,
      stimulate conservation efforts of the perturbed flora and promote sustainable
      exploitation of the medicinal bounty.

PMID- 25952170
TI  - Pathologic basis of pyogenic, nonpyogenic, and other spondylitis and discitis.
AB  - Pyogenic spondylitis and discitis are usually seen following a recent infection
      or surgery. A septic embolus causes an infarcted area within the bone. Pyogenic
      spondylitis is characterized by edema, vascular leakage, and supportive
      inflammatory reaction characterized with polymorphonuclear leukocytes. In
      tuberculosis of the spine, active lesions are characterized by formation of
      epithelioid granulomas with central caseating necrosis. Mycobacterium
      tuberculosis can be shown by histochemical stains for acid-fast bacteria or by
      immunochemistry. In brucella spondylitis, microgranulomatous proliferation
      composed of histiocytes containing numerous bacilli without caseating necrosis is
      characteristic. Brucella melitensis can be shown on histochemical Gram stain. 

PMID- 25952171
TI  - Pathologic approach to spinal cord infections.
AB  - The pathologic evaluation of spinal cord infections requires comprehensive
      clinical, radiological, and laboratory correlation, because the histologic
      findings in acute, chronic, or granulomatous infections rarely provide clues for
      the specific cause. This brief review focuses on the pathologic mechanisms as
      well as practical issues in the diagnosis and reporting of infections of the
      spinal cord. Examples are provided of the common infectious agents and methods
      for their diagnosis. By necessity, discussion is restricted to the infections of
      the medulla spinalis proper and its meninges, and not bone or soft tissue
      infections. 

PMID- 25952169
TI  - Joint associations of insomnia and sleep duration with prevalent diabetes: The
      Hispanic Community Health Study/Study of Latinos (HCHS/SOL).
AB  - BACKGROUND: Inadequate sleep quantity and quality are associated with a higher
      risk of type 2 diabetes. This relationship is not well-examined in U.S.
      Hispanics/Latinos, and prior analyses may be confounded by sleep apnea. This
      cross-sectional study examined joint associations of sleep duration and insomnia
      with diabetes among diverse U.S. Hispanic/Latinos. METHODS: Baseline data on
      sleep quantity and quality were obtained from 15,227 participants (mean age 41;
      range 18-74 years) from the Hispanic Community Health Study/Study of Latinos.
      Complex survey multinomial logistic regression was used to examine associations
      between prevalent diabetes and six phenotypes defined by cross-classifying sleep
      duration (short <=6 h, average >6-9 h, long >9 h) and insomnia, adjusting for
      sex, age, site and Hispanic/Latino background interaction, education, physical
      activity, diet quality, and sleep apnea. RESULTS: In the weighted population, 14%
      had diabetes, 28% had insomnia, 9% were short sleepers, and 19% were long
      sleepers. Compared with those with average sleep and no insomnia, those with
      short sleep and insomnia were more likely to have diabetes (odds ratio [OR] 1.46;
      95% confidence interval [CI] 1.02, 2.11). Average sleepers with insomnia (1.28;
      95% CI 1.02, 1.61) and long sleepers without insomnia (1.33; 95% CI 1.07, 1.65)
      also had elevated odds of diabetes. Further adjustment for body mass index
      attenuated associations, except with long sleep without insomnia. CONCLUSIONS:
      Both decreased quantity and quality of sleep are associated with diabetes in
      Hispanic/Latinos, with the greatest odds among those with short sleep duration
      and insomnia. The association is largely explained by obesity.

PMID- 25952172
TI  - Pediatric spinal infection and inflammation.
AB  - Inflammatory and infectious disorders of the spine in children are less common
      than in adults, and are usually categorized according to location into (1) those
      predominantly affecting the spinal cord; (2) those predominantly affecting the
      nerve roots and meninges; and (3) those predominantly affecting the vertebrae,
      discs, and epidural space. Disorders primitively involving the spinal cord may be
      grouped into 2 basic categories: (1) inflammatory (represented by acute
      transverse myelopathy) and (2) infectious (ie, bacterial, viral, fungal, or
      parasitic). Inflammatory spinal cord diseases are more common than primitive
      spinal cord infection. 

PMID- 25952173
TI  - Pyogenic spinal infections.
AB  - Spinal infections are a spectrum of disease comprising spondylitis, diskitis,
      spondylodiskitis, pyogenic facet arthropathy, epidural infections, meningitis,
      polyradiculopathy, and myelitis. Inflammation can be caused by pyogenic,
      granulomatous, autoimmune, idiopathic, and iatrogenic conditions. In an era of
      immune suppression, tuberculosis, and HIV epidemic, together with worldwide
      socioeconomic fluctuations, spinal infections are increasing. Despite advanced
      diagnostic technology, diagnosis of this entity and differentiation from
      degenerative disease, noninfective inflammatory lesions, and spinal neoplasms are
      difficult. Radiological evaluations play an important role, with contrast
      enhanced MR imaging the modality of choice in diagnosis, evaluation, treatment
      planning, interventional treatment, and treatment monitoring of spinal
      infections. 

PMID- 25952174
TI  - Pediatric and adult spinal tuberculosis: imaging and pathophysiology.
AB  - The prevalence of tuberculosis (TB) has increased in developing and developed
      countries as a consequence of the AIDS epidemic, immigration, social deprivation,
      and inadequate TB control and screening programs. Spinal TB may be osseous or
      nonosseous. Classic findings of multiple contiguous vertebral body involvement,
      gibbus formation, and subligamentous spread with paravertebral abscesses are
      optimally evaluated with MR imaging. Nonspondylitic spinal TB is less well
      described in the literature, may develop in the absence of TB meningitis, and is
      often associated with meningovascular cord ischemia. Radiologists should be
      familiar with the spectrum of imaging findings, allowing early diagnosis and
      treatment of this serious condition. 

PMID- 25952175
TI  - Spinal brucellosis.
AB  - Spinal involvement in human brucellosis is a common condition and a significant
      cause of morbidity and mortality, particularly in endemic areas, because it is
      often associated with therapeutic failure. Most chronic brucellosis cases are the
      result of inadequate treatment of the initial episode. Recognition of spinal
      brucellosis is challenging. Early diagnosis is important to ensure proper
      treatment and decrease morbidity and mortality. Radiologic evaluation has gained
      importance in diagnosis and treatment planning, including interventional
      procedures and monitoring of all spinal infections. 

PMID- 25952176
TI  - Viral infection of the spinal cord and roots.
AB  - This article summarizes myelopathy and radiculopathy caused by different viruses.
      The cases described are divided into three categories: acute myelitis and
      radiculitis, postinfectious myelopathy and radiculopathy, and chronic myelopathy.
      Some diseases present with characteristic imaging findings. For example,
      varicella zoster virus tends to injure the dorsal column, whereas poliovirus
      tends to injure the frontal horns. Magnetic resonance (MR) imaging is an
      essential tool in diagnosis. However, because imaging findings are often
      nonspecific, consideration of a combination of diagnostic procedures, including
      the clinical course, symptoms, and laboratory data, is necessary for making a
      correct diagnosis. 

PMID- 25952177
TI  - Parasitic and rare spinal infections.
AB  - The imaging features of spinal parasitic diseases and other rare infections are
      herein discussed. These diseases are distributed worldwide, with increased
      prevalence in areas with poor sanitary conditions and in developing countries. In
      nonendemic areas, sporadic cases may occur, consequent to increased international
      travel and immunocompromising conditions. Infectious diseases are usually
      treatable, and early detection is often crucial. A thorough comprehension of the
      imaging patterns associated with the clinical features, epidemiology, and
      laboratory results allows the radiologist to narrow down the options for
      differential diagnosis and facilitates the timely implementation of appropriate
      therapies. 

PMID- 25952178
TI  - Image guided interventions in spinal infections.
AB  - Spinal infections are challenging to diagnose and represent a life-threatening
      medical condition. Diagnosis is often delayed because of nonspecific accompanying
      symptoms. The role of interventional neuroradiology in spinal infection is
      double: diagnostic and therapeutic, consisting substantially of 2 main
      procedures, represented by spine biopsies and positioning of percutaneous
      drainage, which represent a minimally invasive, faster and more cost-effective
      alternative to open surgery procedures. This article will focus on the available
      state-of-the-art techniques to perform discovertebral image-guided biopsies in
      case of suspected infections and on image-guided placement of percutaneous
      drainage to treat infectious collections of the spine and paravertebral
      structures. 

PMID- 25952179
TI  - Neurosurgical approaches to spinal infections.
AB  - Spinal infection is rare. Clinical suspicion is important in patients with
      nonmechanical neck and/or back pain to make the proper diagnosis in early
      disease. Before planning surgery, a thorough evaluation of the spinal stability,
      alignment, and deformity is necessary. Timing of surgery, side of approach,
      appropriate surgical technique, and spinal instruments used are crucial.
      Biomechanical preservation of the spinal column during and after the infection is
      a significant issue. Postoperative spine infection is another entity of which
      spinal surgeons should be aware of. Proper septic conditions with meticulous
      planning of surgery are essential for successful spine surgery and better
      outcome. 

PMID- 25952181
TI  - Spinal infections.

PMID- 25952180
TI  - Overview of the complications and sequelae in spinal infections.
AB  - Spondylitis or infection of the spine is a spectrum of diseases involving the
      bone, disks, and/or ligaments. Because of a significant increase in the
      immunocompromised patient population, spinal infections are a growing and
      changing group of conditions, making the diagnosis based on imaging more
      challenging. Most cases of spinal infections are pyogenic and occur after
      hematogeneous spread of an infection located elsewhere in the body. A prompt
      diagnosis remains crucial and MR imaging remains the cornerstone in the
      diagnosis. This article provides a pictorial overview of the complications and
      sequelae in spinal infections in general. Discussed are postoperative infections,
      extraspinal spread of infection, fractures and malformations, and neurologic
      complications. 

PMID- 25952182
TI  - Spinal infection.

PMID- 25952183
TI  - Evolution of centrosomes and the nuclear lamina: Amoebozoan assets.
AB  - The current eukaryotic tree of life groups most eukaryotes into one of five
      supergroups, the Opisthokonta, Amoebozoa, Archaeplastida, Excavata and SAR
      (Stramenopile, Alveolata, Rhizaria). Molecular and comparative morphological
      analyses revealed that the last eukaryotic common ancestor (LECA) already
      contained a rather sophisticated equipment of organelles including a
      mitochondrion, an endomembrane system, a nucleus with a lamina, a microtubule
      organizing center (MTOC), and a flagellar apparatus. Recent studies of MTOCs,
      basal bodies/centrioles, and nuclear envelope organization of organisms in
      different supergroups have clarified our picture of how the nucleus and MTOCs co
      evolved from LECA to extant eukaryotes. In this review we summarize these
      findings with special emphasis on valuable contributions of research on a lamin
      like protein, nuclear envelope proteins, and the MTOC in the amoebozoan model
      organism Dictyostelium discoideum. 

PMID- 25952185
TI  - Visualization of novel microstents in patients with unruptured intracranial
      aneurysms with contrast-enhanced flat panel detector CT.
AB  - OBJECTIVES: The aim of our study was to evaluate the feasibility of contrast
      enhanced flat panel detector CT (FPDCT) for visualizing the novel microstents
      implanted in patients with unruptured wide-necked intracranial aneurysms.
      METHODS: Forty-four cases of patients who underwent stent assisted coiling at our
      department were retrospectively analyzed. In each case, FPDCT images were
      performed after stent and coils deployment and then assessed in the terms of
      stent struts and all radiopaque markers and tantalum strands visibility
      separately using a 3-grade scale (1 - inadequate, 2 - good, 3 - excellent).
      RESULTS: Stent struts visibility was assessed to be inadequate for evaluation in
      all cases. All radiopaque markers and tantalum strands visibility was excellent
      in 61.4% and good in 38.6% of cases. We observed 4 (9.09%) cases of incomplete
      stent opening. Treated aneurysm size <10mm was an independent predictor of
      excellent stent all radiopaque markers and tantalum strands visibility
      (rho=0.014). CONCLUSIONS: Contrast-enhanced FPDCT is feasible for visualizing
      stents implanted in patients with intracranial aneurysms as it gives precise
      visualization of the relationships between the stent tantalum strands and the
      vessel wall. Stents used in the treatment of aneurysms >=10 mm in size are worse
      visualized because of the coil streaking artifacts.

PMID- 25952184
TI  - The role of connexin 43 in mediating odor response.
AB  - Connexin proteins are the hemichannels that form gap junctions to regulate the
      intercellular communication. Connexin 43 (Cx43) is the most common gap junction
      protein that expresses in many cell types, including the olfactory sensory
      neurons. Phosphorylation is a crucial step to regulate the function of Cx43. Gap
      junction was found to modulate the odor response, but the specific role is still
      elusive. Here, we report that gap junctions play a role in odor-evoked calcium
      response in both heterologous cell system and primary olfactory sensory neurons.
      This regulation is mediated through gap junction protein Cx43. Overexpression of
      full length Cx43 can counteract the inhibitory effect of gap junction or connexin
      blockers on odor-evoked [Ca(2+)]i increase in hana3A cells. Carboxy-terminal of
      Cx43 (Cx43CT) has the similar function as the full length of Cx43. Furthermore,
      we found that expression level of phosphorylation of Cx43 at S368 is dynamic with
      the stimulation of odor in hana3A cells. Expression level of phosphorylated Cx43
      at S368 was decreased when gap junction or connexin inhibitors were applied.
      Phosphorylation of Cx43 during odor or inhibitor stimulation may be mediated by
      ERK and JNK signaling pathway. Altogether our data suggest that expression of
      Cx43 can regulate the odor response. This study provides a clue to indicate the
      possible protective mechanism of gap junction in odor response. 

PMID- 25952186
TI  - Aortic annulus eccentricity before and after transcatheter aortic valve
      implantation: Comparison of balloon-expandable and self-expanding prostheses.
AB  - INTRODUCTION: The geometry of the aortic annulus and implanted transcatheter
      aortic valve prosthesis might influence valve function. We investigated the
      influence of valve type and aortic valve calcification on post-implant geometry
      of catheter-based aortic valve prostheses. METHODS: Eighty consecutive patients
      with severe aortic valve stenosis (mean age 82 +/- 6 years) underwent computed
      tomography before and after TAVI. Aortic annulus diameters were determined.
      Influence of prosthesis type and degree of aortic valve calcification on post
      implant eccentricity were analysed. RESULTS: Aortic annulus eccentricity was
      reduced in patients after TAVI (0.21 +/- 0.06 vs. 0.08 +/- 0.06, p<0.0001). Post
      TAVI eccentricity was significantly lower in 65 patients following implantation
      of a balloon-expandable prosthesis as compared to 15 patients who received a self
      expanding prosthesis (0.06 +/- 0.05 vs. 0.15 +/- 0.07, p<0.0001), even though the
      extent of aortic valve calcification was not different. After TAVI, patients with
      a higher calcium amount retained a significantly higher eccentricity compared to
      patients with lower amounts of calcium. CONCLUSIONS: Patients undergoing TAVI
      with a balloon-expandable prosthesis show a more circular shape of the implanted
      prosthesis as compared to patients with a self-expanding prosthesis. Eccentricity
      of the deployed prosthesis is affected by the extent of aortic valve
      calcification.

PMID- 25952187
TI  - Association of Functional Gene Polymorphism with Apical Periodontitis.
AB  - INTRODUCTION: To date, only a few studies have searched for relationships between
      genetic polymorphism and periapical microbial infection. Thus, the purpose of
      this systematic review was to evaluate the relationship between host modifying
      factors and their association with apical periodontitis. METHODS: Two reviewers
      independently conducted a comprehensive literature search. The MEDLINE, Embase,
      Cochrane, and PubMed databases were searched. Additionally, the bibliographies of
      all relevant articles and textbooks were manually searched. RESULTS: Eight
      articles were identified and included in this review. The results of the present
      review suggest that although some authors have reported that some biologic
      markers may play a role in apical periodontitis, others have not supported this
      association. Limitations were noted in the current studies by not judiciously
      matching selected case/control groups, balancing or adjusting for confounders
      (such as smoking, diabetes, and body mass index), using the Hardy-Weinberg
      Equilibrium, providing power calculation for a given sample size, correcting for
      false-positive (type I) error, or providing odds ratios with confidence
      intervals. The results of this review suggest polymorphism and biological
      modifiers, by which some individuals, if challenged by bacterial accumulations,
      may exhibit a more vigorous immunoinflammatory response, leading to apical
      periodontitis. CONCLUSIONS: More research in this area is warranted to determine
      greater specificity in these possible interactions.

PMID- 25952189
TI  - 50th Anniversary Landmark Commentary on Liotta D, Hallman GL, Milam JD, Cooley
      DA. Surgical treatment of acute dissecting aneurysm of the ascending aorta. Ann
      Thorac Surg 1971;12:582-92.

PMID- 25952188
TI  - 50th Anniversary Perspective on Lower, RR, Dong E, Shumway NE. Suppression of
      Rejection Crises in the Cardiac Homograft. Ann Thorac Surg 1965;1:645-9.

PMID- 25952190
TI  - 50th Anniversary Landmark Commentary on Carpentier A, Guermonprez JL, Deloche A,
      Frechette C, DuBost C. The aorta-to-coronary radial artery bypass graft. Ann
      Thorac Surg 1973;16:111-21.

PMID- 25952191
TI  - 50th Anniversary Landmark Commentary on Trinkle JK, Richardson JD, Franz JL,
      Grover FL, Arom KV, Holmstrom FM. Management of flail chest without mechanical
      ventilation. Ann Thorac Surg 1975;19:355-63.

PMID- 25952192
TI  - Invited commentary.

PMID- 25952193
TI  - Invited commentary.

PMID- 25952194
TI  - Invited commentary.

PMID- 25952195
TI  - Invited commentary.

PMID- 25952196
TI  - Invited commentary.

PMID- 25952197
TI  - Invited commentary.

PMID- 25952198
TI  - Invited commentary.

PMID- 25952199
TI  - Invited commentary.

PMID- 25952200
TI  - Invited commentary.

PMID- 25952201
TI  - Invited commentary.

PMID- 25952202
TI  - Invited commentary.

PMID- 25952203
TI  - Invited commentary.

PMID- 25952204
TI  - Invited commentary.

PMID- 25952205
TI  - Invited commentary.

PMID- 25952206
TI  - Invited commentary.

PMID- 25952207
TI  - A novel modified Nuss procedure for pectus excavatum: a new steel bar.
AB  - PURPOSE: The purpose of this article is to introduce a new modified Nuss
      procedure for pectus excavatum and to describe the configuration of the new steel
      bar. DESCRIPTION: We applied a novel method with a new steel bar for minimally
      invasive surgical correction of pectus excavatum. The procedure was performed
      with a new steel bar through bilateral thoracic minimally invasive incisions
      using a thoracoscope for guidance. The bar was installed or removed by pushing
      and pulling without turning it over. EVALUATION: One hundred forty-seven patients
      with pectus excavatum underwent this novel modified Nuss procedure. All patients
      had a satisfactory orthopedic result at discharge. There was no perioperative
      death or cardiac perforation. During the follow-up period, 134 patients underwent
      bar removal. Of the 134 cases, the initial orthopedic and functional results were
      excellent in 121 patients (90.3%) and good in 13 patients (9.7%). No patient had
      recurrence. CONCLUSIONS: This novel modified Nuss procedure is a safe, effective,
      and convenient treatment for pectus excavatum.

PMID- 25952208
TI  - Pre- and post- transplantation lung cancer in heart transplant recipients.
AB  - Heart transplantation after lung cancer surgery can be questionable because of
      the high risk of cancer recurrence. We report the results of two patients. The
      first underwent right lobectomy in 2008 for pT1N0 adenocarcinoma, heart
      transplantation in 2010, and surgery for synchronous adenocarcinoma and squamous
      cell carcinoma in 2012. The second underwent left segmentectomy for pT1aN0
      adenosquamous carcinoma and transplantation in 1995 and then surgery for pT1aN1
      adenocarcinoma in 2013. Posttransplantation lung cancer histologic analysis
      results were different in both cases, demonstrating the absence of metastatic
      recurrence. Thus, early stage lung cancer might not be a contraindication to
      heart transplantation, nor are long delays be necessary before registering on a
      waiting list. 

PMID- 25952209
TI  - Patient-controlled conditioning for left ventricular assist device-induced
      myocardial recovery.
AB  - Although medical protocols exist to promote reverse remodeling in left
      ventricular assist device-supported patients, there are scant data about device
      management in these patients. We report the use of a Jarvik 2000 left ventricular
      assist device (Jarvik Heart Inc, New York, NY) to facilitate myocardial recovery
      leading to device explantation using a sequential, patient-controlled approach.
      Sequential conditioning of the left ventricular assist device-supported heart is
      a promising strategy for bridging patients to recovery and pump removal.

PMID- 25952210
TI  - Mitraclip procedure as a bridge therapy in a patient with heart failure listed
      for heart transplantation.
AB  - Functional mitral regurgitation (MR) is frequently detected in patients with
      dilated cardiomyopathy and advanced heart failure, worsening quality of life and
      predicting poor survival. However, the optimal treatment of patients with
      advanced heart failure and severe MR has been controversial. We present the case
      of a 55-year-old man with previous aortic valve replacement, severe MR with high
      grade pulmonary hypertension, and refractory heart failure (HF). He was listed
      for cardiac transplant and underwent percutaneous MitraClip implantation as
      bridge therapy. The postoperative course was uneventful, with significant
      improvement in New York Heart Association functional class. The patient underwent
      a successful heart transplant 8 months after the procedure. 

PMID- 25952211
TI  - Large primary right ventricular teratoma in an adult.
AB  - We report an unusual case of a 30-year-old man with a primary mature cystic
      teratoma in the right ventricle. This case constitutes the third case of primary
      intramyocardial teratoma in an adult and the first that describes its benign
      form. In this report, we discuss surgical implications of such a rare cardiac
      tumor. 

PMID- 25952212
TI  - Endovascular repair of a Kommerell diverticulum anomaly.
AB  - A Kommerell diverticulum (KD) may predispose toward aortic aneurysm, dissection,
      or rupture, although they are primarily asymptomatic. We report a case of an
      aberrant left subclavian artery arising from a KD in a right-side aortic arch.
      The lesions were successfully treated by an endovascular approach involving
      Amplatzer vascular plug embolization of the aberrant left subclavian artery and
      endovascular repair of the KD. 

PMID- 25952213
TI  - Rare Case of Aortopulmonary Window With Anomalous Origin of Right Coronary
      Artery.
AB  - A 5-month-old infant presented with a rare, congenital heart disease:
      aortopulmonary window with an anomalous origin of the right coronary artery from
      the aortopulmonary window. Using echocardiography and computed tomography, the
      exact diagnosis could only be ascertained retrospectively; however, cardiac
      catheterization and angiography confirmed the diagnosis, which led to elective
      open-heart surgery. The infant made a full recovery. 

PMID- 25952214
TI  - De novo obstruction after supravalvular aortic stenosis repair in Williams-Beuren
      syndrome.
AB  - Williams-Beuren syndrome is characterized by diffuse arteriopathy due to elastin
      gene deficiency. We present a patient with de novo supravalvular stenosis due to
      excessive intimal hyperplasia after a previous repair. This case report supports
      in vitro and animal studies that have linked elastin deficiency to increased
      cellular proliferation in the vessel wall with the subsequent development of
      obstructive lesions.

PMID- 25952215
TI  - Thoracoscopic surgery for multiple peripheral pulmonary arteriovenous fistulas.
AB  - A 37-year-old woman with dyspnea was referred to our department with the
      diagnosis of multiple bilateral pulmonary arteriovenous fistulas. Computed
      tomography of the chest showed nine fistulas in the right lung and four in the
      left lung. Because the fistulas were small and located peripherally, we chose
      thoracoscopic surgery instead of transcatheter pulmonary artery embolization.
      Intraoperatively, we identified four additional fistulas in the left lung. We
      resected 15 abnormal vessels and ligated two vessels during thoracoscopic
      surgery. Postoperatively, her dyspnea decreased and arterial blood oxygenation
      improved. Thoracoscopic surgery is a good treatment option for multiple small
      peripheral pulmonary arteriovenous fistulas. 

PMID- 25952216
TI  - Conservatively treated extended tracheal necrosis complicating
      pharyngolaryngectomy.
AB  - Tracheal necrosis is a rare life-threatening phenomenon that most often occurs
      after thyroid operations or prolonged intubation. Conservative treatment can be
      one choice in extensive tracheal necrosis. We report the case of a 59-year-old
      man, with tracheal necrosis that developed after pharyngolaryngectomy, that we
      treated conservatively using hyperbaric oxygen therapy and antibiotic therapy.
      The follow-up was assured by tracheobronchoscopy. A year after his discharge, the
      trachea was totally healed. 

PMID- 25952217
TI  - A malignant glomus tumor in the upper trachea.
AB  - Malignant glomus tumors are extremely rare, and a malignant glomus tumor in the
      trachea has not been described previously. In this report, we present the first
      known case of a malignant glomus tumor originating in the trachea. 

PMID- 25952218
TI  - Pulmonary endarterectomy for pulmonary hypertension from septic emboli.
AB  - Pulmonary endarterectomy (PEA) can significantly increase long-term survival in
      patients with chronic thromboembolic pulmonary hypertension; however, the role of
      PEA for chronic thromboembolic pulmonary hypertension due to pulmonary valve
      endocarditis is controversial. A critically ill 61-year-old man with intractable
      right ventricular heart failure was found to have chronic thromboembolic
      pulmonary hypertension due to Streptococcus bovis pulmonary valve endocarditis
      and underwent successful pulmonary valve replacement and PEA. The successful
      outcome in this case suggests that PEA should be considered in patients with this
      condition. 

PMID- 25952219
TI  - Endobronchial ultrasound-guided diagnosis of pulmonary artery tumor embolus.
AB  - A patient diagnosed with pulmonary embolism had persistent symptoms despite
      adequate therapy. Tissue sampling with endobronchial ultrasound-guided needle
      aspiration revealed endovascular metastasis from a prior early-stage colorectal
      cancer. We describe the challenges in the diagnosis and workup of suspected tumor
      emboli. 

PMID- 25952221
TI  - Spontaneous herniation of the lung and diaphragm treated with surgical repair.
AB  - Lung herniation is rare and is usually caused by blunt trauma, congenital
      abnormalities of the ribs, or previous thoracic operations. We report a rare case
      of spontaneous lung herniation in a 72-year-old woman and describe the operative
      repair. 

PMID- 25952220
TI  - Use of Extended-Criteria Lungs on a Lobe-by-Lobe Basis Through Ex Vivo Lung
      Perfusion Assessment.
AB  - Initially rejected and extended-criteria lungs were partially used through an ex
      vivo lung perfusion (EVLP) assessment that was first clinically applied in Asia.
      The truly injured lobe (left lower lobe) was identified during 89-minute
      normothermic EVLP and was excised, and the remaining lobes were successfully
      transplanted into a patient with lymphangioleiomyomatosis. The lung lobes showed
      heterogeneous changes on the ex vivo rig, and a brief duration of EVLP helped
      differentiate lung quality on a lobe-by-lobe basis.

PMID- 25952222
TI  - Small and large bowel hernia migrated into the chest 6 years after sternal
      resection.
AB  - Sternal resection represents a rare, peculiar subgroup of chest wall operations.
      Abdominal or lung hernia could be a serious complication after extended chest
      wall or sternal resection for cancer. We present a case of a late abdominal
      hernia in the chest underneath the skin, 7 years after a total sternal resection
      for a sarcoma. 

PMID- 25952223
TI  - Huge left atrial appendage after an incomplete surgical ligation and successful
      catheter ablation of atrial fibrillation.

PMID- 25952224
TI  - Intraoperative identification of chyle leak during coarctation repair using
      fluorescein dye.

PMID- 25952225
TI  - Intravascular pulmonary migration of a subdermal contraceptive implant.

PMID- 25952226
TI  - Right lower sleeve lobectomy with double-barreled bronchoplasty for a centrally
      located lung cancer.

PMID- 25952227
TI  - Neo-ostium creation for anomalous aortic origin of the coronary artery.
AB  - For the anomalous aortic origin of the coronary artery with interarterial course,
      surgical repair is recommended. We describe a technique of neo-ostium creation at
      the correct anatomic position for the right coronary artery arising from a single
      left coronary ostium without an intramural course and coursing between the
      ascending aorta and the main pulmonary artery. 

PMID- 25952228
TI  - Coronary reimplantation in aortic root surgery: the trapdoor technique for
      adults.
AB  - Coronary ostial reimplantation during aortic root replacement is a key stage of
      the operation. The "button technique" is the most used method, but there are
      still concerns about the incidence of coronary pseudoaneurysm formation,
      bleeding, and distortion of the coronary geometry. We describe how we adapted the
      trapdoor technique, commonly used in the arterial switch operation in children,
      to reimplant the coronary ostia in adult patients undergoing aortic root
      replacement. 

PMID- 25952229
TI  - Z-type pattern pectus excavatum/carinatum in a case of Noonan syndrome.
AB  - Noonan syndrome is a genetic condition that can present with complex thoracic
      defects, the management of which often presents a surgical challenge. We present
      the surgical approach applied to a severe combined excavatum/carinatum deformity
      that had resulted in a Z-type configuration of the chest in a 9-year-old girl
      with Noonan syndrome. 

PMID- 25952230
TI  - Computed tomographically guided injection of cyanoacrylate in association with
      preoperative radioguided occult lesion localization of ground-glass opacities.
AB  - Intraoperative localization of a ground-glass opacity (GGO) is difficult because
      it is not easy to palpate and may be invisible at radioscopy. Therefore various
      techniques have been developed to improve intraoperative localization of these
      lesions, allowing adequate surgical resection. We report 2 cases of preoperative
      localization of GGOs through computed tomographically guided injection of
      cyanoacrylate in association with radioguided occult lesion localization (ROLL). 

PMID- 25952231
TI  - Is It Time to Revisit Surgical Lung Biopsy in ARDS?

PMID- 25952232
TI  - Reply: To PMID 19272548.

PMID- 25952233
TI  - Perioperative strict or flexible glycemic control strategy may not have a
      predictive value on patient survival after coronary bypass grafting.

PMID- 25952234
TI  - The Nuss procedure: above all, do no harm.

PMID- 25952235
TI  - Reply: To PMID 25134860.

PMID- 25952236
TI  - Devices for a clampless approach to coronary artery operations: effect on stroke
      rate.

PMID- 25952237
TI  - Accessory miniature mitral valve causing subaortic obstruction.

PMID- 25952238
TI  - Reply: To PMID 24726605.

PMID- 25952239
TI  - Reply: To PMID 24996724.

PMID- 25952240
TI  - Low-Dose Recombinant Activated Factor VII (rF-VIIa) for Excess Hemorrhage After
      Cardiac Operation.

PMID- 25952241
TI  - Transapical mitral valve-in-valve implantation for patients in cardiogenic shock.
AB  - Transcatheter aortic valve implantation has demonstrated excellent results in
      high risk and inoperable patients, and been extended to valve-in-valve
      implantation for those with prosthetic aortic and, more recently, mitral valve
      failure. Despite its use in high risk and inoperable patients, active cardiogenic
      shock has historically been considered a contraindication. We describe 2 patients
      in acute cardiogenic shock from prosthetic mitral valve failure treated with
      transcatheter mitral valve-in-valve implantation. Transcatheter mitral valve
      therapies should be considered in patients in cardiogenic shock from prosthetic
      mitral valve failure, although, larger studies are needed to make any strong
      recommendation. 

PMID- 25952242
TI  - Aorto-azygous fistula complicated by arteriovenous aneurysm treated with video
      assisted thoracic surgery.
AB  - Congenital arteriovenous fistula complicated by arteriovenous aneurysm is very
      rare. We report a case of a 23-year-old man diagnosed with an asymptomatic
      congenital aorto-azygous fistula complicated by an arteriovenous aneurysm. Video
      assisted thoracoscopic surgery (VATS) was successfully performed to resect the
      abnormal feeding artery and ligate the draining azygos vein. There were no
      postoperative complications, and late follow-up showed a satisfactory outcome.
      Our experience indicates that VATS is a safe and appropriate option to treat this
      kind of vascular malformation. 

PMID- 25952243
TI  - Recurrent angina caused by coronary subclavian steal syndrome confirmed by
      positron emission tomography.
AB  - Coronary subclavian steal syndrome is a rare cause of recurrent angina after
      coronary artery bypass grafting. Identification of the myocardial ischemic region
      is crucial because it guides revascularization interventions to improve symptoms
      and myocardial ischemia. Positron emission computed tomography (PET) with
      rubidium might be a helpful tool because it identifies ischemia, localizes more
      precisely the ischemic region, and evaluates coronary flow reserve. Here, we
      report a case of recurrence of angina after coronary artery bypass grafting
      caused by an obstruction in the left subclavian artery and consequently by
      coronary steal syndrome confirmed by PET. 

PMID- 25952244
TI  - Pericardioscopy for diagnosing penetrating cardiac trauma.
AB  - Currently, the diagnosis of hemopericardium in trauma is made mainly by
      ultrasonography. A pericardial window, either through thoracoscopy or by a
      subxiphoid approach, is also used. However, hemopericardium per se might be
      overly sensitive for diagnosing cardiac injuries after chest trauma. The use of
      diagnostic pericardioscopy in a hemodynamically stable patient with penetrating
      cardiac trauma is presented. This procedure excluded significant cardiac injury
      and spared the patient from a major nontherapeutic procedure. 

PMID- 25952245
TI  - Staged biventricular repair for absent aortic valve in a neonate.
AB  - Congenitally absent aortic valve is an extremely rare and fatal cardiac
      malformation. We report the case of a neonate with absent aortic valve, an
      interrupted aortic arch, and a normal-sized left ventricle. At age 9 hours,
      emergency aortic valve closure and a Norwood procedure were performed to maintain
      coronary circulation. The patient's postoperative course was complicated because
      of tracheomalacia and a severely dilated aorta that were treated with reduction
      aortoplasty at age 4 months. Finally, a staged Yasui procedure was performed at
      26 months. To our knowledge, this is the first report of a successful
      biventricular repair for absent aortic valve. 

PMID- 25952246
TI  - Artery fistula causing aortic regurgitation in pulmonary atresia with ventricular
      septal defect and major aortopulmonary collateral arteries.
AB  - We report a case of aortic regurgitation (AR), coronary artery-to-pulmonary
      artery (CAPA) fistula, pulmonary atresia with ventricular septal defect (PA/VSD),
      and major aortopulmonary collateral arteries (MAPCAS). As a result of coronary
      steal and AR, myocardial ischemia and ventricular dysfunction occurred. When the
      patient was 2 months old with a body weight of 2.7 kg, we performed fistula
      ligation, aortic valvuloplasty, unifocalization of the MAPCAS, and right
      ventricle-to-pulmonary artery shunting. After the operation, the AR volume
      reduced, and the patient was scheduled for repair. 

PMID- 25952247
TI  - Misdiagnosis of a small cell lung cancer resulting from inaccurate pathology.
AB  - Currently, a biopsy provides the most reliable evidence for diagnosing a disease,
      and the majority of doctors do not question the diagnosis made by a pathologist.
      However, an inaccurate diagnosis may lead to serious consequences; for example, a
      benign tumor may be misdiagnosed as a malignancy, or a malignancy may be deemed
      to be benign. How to avoid these types of mistakes is a continuing issue of
      concern to all doctors. Here, we report a case of small cell lung cancer
      misdiagnosed as an inflammatory myofibroblastic tumor. Fortunately, we performed
      a mediastinoscopy on the patient and discovered the actual pathologic condition.
      This case is presented to caution against the possibility of the misdiagnosis of
      uncommon diseases in clinical practice. 

PMID- 25952248
TI  - Percutaneous transcatheter closure of the aortic valve.

PMID- 25952249
TI  - Neurocognitive and neuroimaging outcome of early treated young adult PKU
      patients: A longitudinal study.
AB  - The aim of the study was to explore the outcome of neurocognitive deficits and
      neuroimaging correlates in young adult early treated phenylketonuric (PKU)
      patients. We conducted a longitudinal study of 14 PKU patients that were assessed
      for IQ and neuropsychological functioning including executive functions (EF) over
      14 years of follow-up (age range at 1st and 2nd assessments were 7.8-13.5 and
      22.2-27.7 years, respectively). The IQ of all 14 PKU patients was within the
      normal range. With respect to the 1st assessment, mean IQ at follow-up did not
      decrease significantly. Compared to control subjects (n = 14), mean IQ of
      patients was significantly lower (p = .0005). Throughout adolescence and early
      adulthood there was an improvement of neuropsychological functioning of PKU
      patients in spite of the relaxation of diet, however some deficits were still
      detectable when compared to controls. All patients that underwent a second MRI
      scan showed white matter alterations ranging from mild to severe which was
      correlated neither with IQ nor with EF scoring. Cognitive, neuropsychological and
      neuroimaging outcome was influenced from life-long and/or second decade of life
      metabolic control. Nevertheless patients' developmental trajectories were in some
      cases independent from metabolic control. Our results support the hypothesis of
      an individual vulnerability to phenylalanine. However, as long as individual
      factors that account for the vulnerability to Phe are not recognized, strict
      dietary control is recommended for all the patients also in the second decade of
      life.

PMID- 25952250
TI  - Embryos, DOHaD and David Barker.
AB  - The early embryo and periconceptional period is a window during which
      environmental factors may cause permanent change in the pattern and
      characteristics of development leading to risk of adult onset disease. This has
      now been demonstrated across small and large animal models and also in the human.
      Most evidence of periconceptional 'programming' has emerged from maternal
      nutritional models but also other in vivo and in vitro conditions including
      assisted reproductive treatments, show consistent outcomes. This short review
      first reports on the range of environmental in vivo and in vitro periconceptional
      models and resulting long-term outcomes. Second, it uses the rodent maternal low
      protein diet model restricted to the preimplantation period and considers the
      stepwise maternal-embryonic dialogue that comprises the induction of programming.
      This dialogue leads to cellular and epigenetic responses by the embryo, mainly
      identified in the extra-embryonic cell lineages, and underpins an apparently
      permanent change in the growth trajectory during pregnancy and associates with
      increased cardiometabolic and behavioural disease in adulthood. We recognize the
      important advice of David Barker some years ago to investigate the sensitivity of
      the early embryo to developmental programming, an insight for which we are
      grateful. 

PMID- 25952251
TI  - Prenatal exposure to maternal stress following bereavement and cardiovascular
      disease: A nationwide population-based and sibling-matched cohort study.
AB  - AIMS: Cardiovascular disease (CVD) is among the leading determinants of mortality
      and morbidity, and causation may begin in the early intrauterine environment.
      Prenatal exposures to glucocorticoids or stress are potential risk factors of CVD
      later in life, but empirical evidence from large population studies is lacking.
      We explored the association between prenatal stress due to maternal bereavement
      following the death of a relative and CVD in the exposed offspring. METHODS AND
      RESULTS: This population-based study included 2,607,851 children born in Denmark
      (1970-2008). Of these participants, 73,708 (2.8%) had a CVD event during follow
      up (up to 40 years). A total of 50,940 (2.0%) subjects born to mothers who lost a
      relative during pregnancy or the year before were categorized as exposed. Cox
      Proportional Hazards models were used to analyse the data. The overall hazard
      ratio (HR) (95% confidence interval) of having a CVD was 1.13 (1.06-1.20); the
      estimate was 1.24 (1.11-1.38) for heart disease and 1.27 (1.01-1.60) for
      hypertension. Additional sibling-matched analyses showed an overall attenuated
      association (1.08 (0.94-1.24)). CONCLUSION: Our results suggested a modest
      association between prenatal stress and CVD, both in childhood and early
      adulthood, which could be of importance, especially at an older age when the
      individuals are followed over a long period.

PMID- 25952252
TI  - Opioids in hip fracture patients: an analysis of mortality and post hospital
      opioid use.
AB  - OBJECTIVE: The aim of this study was to investigate the use of opioids among hip
      fracture patients, and the potential relation between perioperative prescription
      of opioids, mortality and chronic opioid use. The purpose of this study was to
      investigate the use of opioids among hip fracture patients postoperatively and 90
      and 180 days after discharge. The study also analysed predictors of early death
      at 30-, 90 and 365 days after discharge. METHODS: We present data from the
      Orthopaedic Department at Bispebjerg University Hospital from 30 May 2010 and 31
      March 2011 on 416 consecutively admitted hip fracture patients. Three patients
      died before surgery and were excluded from the analyses. Data were collected
      through medical records, hospital and national databases. Medication use was
      analysed before admission, at 3 and 6 months. Mortality data were analysed at 30
      days, 6 months and 1 year. RESULTS: 24% were opioid users at admission, of whom
      13% had an active malignant disease and 20% had been diagnosed with osteoporosis.
      95% received opioids during admission, and 81% received a prescription for
      opioids at discharge. This fraction decreased to 36% at 3 months and 30% at 6
      months. 2.9% of previous opioid naive patients remained users at 6 months. Opioid
      use prior to admission and a pre-existing diagnosis of osteoporosis were the most
      significant factors associated with continued use at 3 and 6 months. The 30-day
      mortality was 10% and 1-year mortality was 27%. Mortality was associated with
      high age, ASA score>2, active cancer, high creatinine and leucocytosis. We found
      no association between opioids and mortality. CONCLUSION: The results of our
      study indicate no general reason to refrain from prescribing opioids to hip
      fracture patients based on a fear of potential abuse or increased mortality.

PMID- 25952253
TI  - Association of homoarginine and methylarginines with liver dysfunction and
      mortality in chronic liver disease.
AB  - Previous studies on arginine metabolites reported an association of asymmetric
      dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) with liver
      dysfunction and an inverse relation of homoarginine (hArg) with cardiovascular
      risk. The aim of the present study was to investigate the relationships between
      hArg, ADMA, SDMA, and the dimethylarginine score (DAS, i.e., ADMA + SDMA) and
      liver dysfunction and survival in chronic liver disease. In 94 consecutive
      cirrhotic patients admitted to our outpatient liver clinic, serum levels of hArg,
      ADMA, and SDMA were measured by HPLC at baseline. Patients were followed with
      respect to mortality. In the entire study cohort (age 58.5 +/- 11.2 years; 31 %
      females), the serum concentrations were 1.94 +/- 0.90 uM for homoarginine, 0.90
      +/- 0.22 uM for ADMA, and 0.70 (0.60-0.93) uM for SDMA. ADMA correlated with both
      Child-Pugh and MELD scores, while SDMA, DAS, and hArg correlated with MELD score
      only. Thirty patients (32 %) died during a median follow-up of 3.5 years. Age-
      and sex-adjusted Cox proportional hazard ratios (HR) per uM (with 95 % confidence
      intervals) showed that hArg was associated with decreased mortality [HR 0.59
      (0.37-0.96)], whereas mortality was increased in patients with higher ADMA [HR
      3.78 (0.98-14.60)], SDMA [HR 6.54 (3.15-13.59)] and DAS [HR 4.13 (2.26-7.56)].
      Only SDMA and DAS remained significantly associated with mortality after
      additional adjustments for either Child-Pugh stage or MELD score. In conclusion,
      in cirrhotic patients seen in an outpatient liver clinic, hArg as well as the
      dimethylarginines ADMA and SDMA was related to long-term mortality. In
      particular, SDMA predicts mortality independently of both Child-Pugh stage and
      MELD score.

PMID- 25952254
TI  - SmART-ER imaging and treatment of glioblastoma.

PMID- 25952255
TI  - The relationship between symptoms and blood pressure during maintenance
      hemodialysis.
AB  - Intradialytic hypotension (IDH) is a detrimental complication of maintenance
      hemodialysis, but how it is defined and reported varies widely in the literature.
      European Best Practice Guideline and Kidney Disease Outcomes Quality Initiative
      guidelines require symptoms and a mitigating intervention to fulfill the
      diagnosis, but morbidity and mortality outcomes are largely based on blood
      pressure alone. Furthermore, little is known about the incidence of asymptomatic
      hypotension, which may be an important cause of hypoperfusion injury and impaired
      outcome. Seventy-seven patients were studied over 456 dialysis sessions. Blood
      pressure was measured at 15-minute intervals throughout the session and compared
      with post-dialysis symptom questionnaire results using mixed modeling to adjust
      for repeated measures in the same patient. The frequency of asymptomatic
      hypotension was estimated by logistic regression using a variety of commonly
      cited blood pressure metrics that describe IDH. In 113 sessions (25%) where
      symptoms were recorded on the questionnaire, these appear not to have been
      reported to dialysis staff. When symptoms were reported (293 sessions [64%]), an
      intervention invariably followed. Dizziness and cramp were strongly associated
      with changes in systolic blood pressure (SBP), but not diastolic blood pressure.
      Nausea occurred more frequently in younger patients but was not associated with
      falls in blood pressure. Thresholds that maximized the probability of an
      intervention rather than a session remaining asymptomatic were SBP <100 mmHg or a
      20% reduction in SBP from baseline. The probability of SBP falling to <100 mmHg
      in an asymptomatic session was 0.23. Symptoms are frequently not reported by
      patients who are hypotensive during hemodialysis, which leads to an
      underestimation of IDH if symptom-based definitions are used. A revised
      definition of IDH excluding patient-reported symptoms would be in line with
      literature reporting morbidity and mortality outcomes and include sessions in
      which potentially detrimental asymptomatic hypotension occurs. 

PMID- 25952258
TI  - BK and JC polyomavirus infections in Tunisian renal transplant recipients.
AB  - The aim of this prospective study was to investigate the rate of BK (BKPyV) and
      JC (JCPyV) polyomavirus infections and their influence on allograft function in
      Tunisian renal transplant recipients. A total of 72 renal transplant recipients
      were studied. BKPyV and JCPyV were detected and quantified by real-time PCR in
      urine and plasma. Demographic and laboratory characteristics were collected for
      each patient. Polyomavirus DNAuria was detected in 54 (75%) of renal transplant
      recipients: 26 (36%) had BKPyV DNAuria, 20 (28%) had JCPyV DNAuria, and 8 (11%)
      had a dual BKPyV/JCPyV DNAuria. BKPyV DNAemia was detected in four (5.5%)
      patients, whereas no patient had JCPyV viremia. More than 70% of BKPyV and JCPyV
      infections started within the first 3 months post-transplant. The risk for
      positive DNAemia was observed in patients with DNAuria level >10(7) copies/ml. BK
      Polyomavirus-associated nephropathy (BKPyVAN) was observed in two patients. This
      study highlights the high frequency of BKPyV and JCPyV viruria during the first
      year post-transplant with the highest incidence observed in the third month. We
      identified several risk factors that were associated with BKV DNAuria including
      age, sex of patients, and the use of tacrolimus instead of cyclosporine A at
      month 3. The use of cyclosporine A instead of tacrolimus was identified as risk
      factor for JCV viruria in month 3. No statistical difference in the allograft
      function was found between BKPyV and/or JCPyV infected and uninfected patients.

PMID- 25952257
TI  - Intraoperative High-Dose Dexamethasone and Severe AKI after Cardiac Surgery.
AB  - Administration of prophylactic glucocorticoids has been suggested as a strategy
      to reduce postoperative AKI and other adverse events after cardiac surgery
      requiring cardiopulmonary bypass. In this post hoc analysis of a large placebo
      controlled randomized trial of dexamethasone in 4465 adult patients undergoing
      cardiac surgery, we examined severe AKI, defined as use of RRT, as a primary
      outcome. Secondary outcomes were doubling of serum creatinine level or AKI-RRT,
      as well as AKI-RRT or in-hospital mortality (RRT/death). The primary outcome
      occurred in ten patients (0.4%) in the dexamethasone group and in 23 patients
      (1.0%) in the placebo group (relative risk, 0.44; 95% confidence interval, 0.19
      to 0.96). In stratified analyses, the strongest signal for potential benefit of
      dexamethasone was in patients with an eGFR<15 ml/min per 1.73 m(2). In
      conclusion, compared with placebo, intraoperative dexamethasone appeared to
      reduce the incidence of severe AKI after cardiac surgery in those with advanced
      CKD. 

PMID- 25952264
TI  - Variability in Cancer Risk with BRCA Mutations.

PMID- 25952256
TI  - The Future of Polycystic Kidney Disease Research--As Seen By the 12 Kaplan
      Awardees.
AB  - Polycystic kidney disease (PKD) is one of the most common life-threatening
      genetic diseases. Jared J. Grantham, M.D., has done more than any other
      individual to promote PKD research around the world. However, despite decades of
      investigation there is still no approved therapy for PKD in the United States. In
      May 2014, the University of Kansas Medical Center hosted a symposium in Kansas
      City honoring the occasion of Dr. Grantham's retirement and invited all the
      awardees of the Lillian Jean Kaplan International Prize for Advancement in the
      Understanding of Polycystic Kidney Disease to participate in a forward-thinking
      and interactive forum focused on future directions and innovations in PKD
      research. This article summarizes the contributions of the 12 Kaplan awardees and
      their vision for the future of PKD research. 

PMID- 25952265
TI  - The influence of poly(ethylene glycol) ether tetrasuccinimidyl glutarate on the
      structural, physical, and biological properties of collagen fibers.
AB  - Various chemical, natural, or synthetic in origin, crosslinking methods have been
      proposed over the years to stabilise collagen fibers. However, an optimal method
      has yet to be identified. Herein, we ventured to assess the potential of 4-star
      poly(ethylene glycol) ether tetrasuccinimidyl glutarate, as opposed to
      glutaraldehyde (GTA), genipin and carbodiimide, on the structural, physical and
      biological properties of collagen fibers. The 4-star poly(ethylene glycol) ether
      tetrasuccinimidyl glutarate induced an intermedium surface smoothness,
      denaturation temperature and swelling. The 4-star poly(ethylene glycol) ether
      tetrasuccinimidyl glutarate fibers had significantly higher stress at break
      values than the carbodiimide fibers, but significantly lower than the GTA and
      genipin fibers. With respect to strain at break, no significant difference was
      observed among the crosslinking treatments. The 4-star poly(ethylene glycol)
      ether tetrasuccinimidyl glutarate fibers exhibited significantly higher cell
      metabolic activity and DNA concentration that all other crosslinking treatments,
      promoted consistently cellular elongation along the longitudinal fiber axis and
      by day 7 they were completely covered by cells. Collectively, this work clearly
      demonstrates the potential of 4-star poly(ethylene glycol) ether
      tetrasuccinimidyl glutarate as collagen crosslinker. (c) 2015 Wiley Periodicals,
      Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 914-922, 2016.

PMID- 25952266
TI  - Unveiling of novel regio-selective fatty acid double bond hydratases from
      Lactobacillus acidophilus involved in the selective oxyfunctionalization of mono-
      and di-hydroxy fatty acids.
AB  - The aim of this study is the first time demonstration of cis-12 regio-selective
      linoleate double-bond hydratase. Hydroxylation of fatty acids, abundant feedstock
      in nature, is an emerging alternative route for many petroleum replaceable
      products thorough hydroxy fatty acids, carboxylic acids, and lactones. However,
      chemical route for selective hydroxylation is still quite challenging owing to
      low selectivity and many environmental concerns. Hydroxylation of fatty acids by
      hydroxy fatty acid forming enzymes is an important route for selective
      biocatalytic oxyfunctionalization of fatty acids. Therefore, novel fatty acid
      hydroxylation enzymes should be discovered. The two hydratase genes of
      Lactobacillus acidophilus were identified by genomic analysis, and the expressed
      two recombinant hydratases were identified as cis-9 and cis-12 double-bond
      selective linoleate hydratases by in vitro functional validation, including the
      identification of products and the determination of regio-selectivity, substrate
      specificity, and kinetic parameters. The two different linoleate hydratases were
      the involved enzymes in the 10,13-dihydroxyoctadecanoic acid biosynthesis.
      Linoleate 13-hydratase (LHT-13) selectively converted 10 mM linoleic acid to 13S
      hydroxy-9(Z)-octadecenoic acid with high titer (8.1 mM) and yield (81%). Our
      study will expand knowledge for microbial fatty acid-hydroxylation enzymes and
      facilitate the designed production of the regio-selective hydroxy fatty acids for
      useful chemicals from polyunsaturated fatty acid feedstocks.

PMID- 25952267
TI  - Management of glucocorticoid-induced osteoporosis: clinical data in relation to
      disease demographics, bone mineral density and fracture risk.
AB  - INTRODUCTION: Glucocorticoid-induced osteoporosis (GIOP) is the most common type
      of secondary osteoporosis. Patient selection and the treatment choice remain to
      be controversial. None of the proposed management guidelines are widely accepted.
      We evaluate the available clinical data, the efficacy of current medication and
      we propose an overall algorithm for managing GIOP. AREAS COVERED: This article
      provides a critical review of in vivo and clinical evidence regarding GIOP and
      developing evidence-based algorithm of treatment. Data base used includes
      MEDLINE(r) (1950 to May 2014). EXPERT OPINION: Patient-specific treatment is the
      gold standard of care. Glucocorticoid (GC)-treated patients must comply with a
      healthy lifestyle and receive 1000 mg of calcium and at least 800 mg of Vitamin D
      daily. Bisphosphonate (BP) therapy is the current standard of care for prevention
      and treatment of GIOP. Most of bisphosphonates demonstrated benefit in lumbar
      bone mineral density (BMD) and some in hip BMD. Alendronate, risedronate and
      zoledronate showed vertebral anti-fracture efficacy in postmenopausal women and
      men. Scarce data however when compared head to head with BP efficacy. In post
      menopausal women, early antiresorptive BP treatment appears to be efficient and
      safe. In premenopausal women and patients at high risk of fracture receiving long
      term GC therapy however, teriparitide may be advised alternatively.

PMID- 25952269
TI  - Response to the CDC report on death in children with epilepsy.

PMID- 25952268
TI  - Preliminary results of the global audit of treatment of refractory status
      epilepticus.
AB  - The treatment of refractory and super refractory status epilepticus is a "terra
      incognita" from the point of view of evidence-based medicine. As randomized or
      controlled studies that are sufficiently powered are not feasible in relation to
      the many therapies and treatment approaches available, we carried out an online
      multinational audit (registry) in which neurologists or intensivists caring for
      patients with status epilepticus may prospectively enter patients who required
      general anesthesia to control the status epilepticus (SE). To date, 488 cases
      from 44 different countries have been collected. Most of the patients had no
      history of epilepsy and had a cryptogenic etiology. First-line treatment was
      delayed and not in line with current guidelines. The most widely used anesthetic
      of first choice was midazolam (59%), followed by propofol and barbiturates.
      Ketamine was used in most severe cases. Other therapies were administered in 35%
      of the cases, mainly steroids and immunotherapy. Seizure control was achieved in
      74% of the patients. Twenty-two percent of patients died during treatment, and
      four percent had treatment actively withdrawn because of an anticipated poor
      outcome. The neurological outcome was good in 36% and poor in 39.3% of cases,
      while 25% died during hospitalization. Factors that positively influenced outcome
      were younger age, history of epilepsy, and low number of different anesthetics
      tried. This article is part of a Special Issue entitled "Status Epilepticus". 

PMID- 25952270
TI  - Wider neck circumference is related to severe asthma in children.
AB  - BACKGROUND: Obesity is an established risk factor for asthma in children.
      Measures of central obesity are reported to be more associated with the severity
      of asthma in adults. The aim of the study was to investigate the association
      between fat distribution, which is determined by anthropometric measures
      including neck circumference (NC) and asthma severity in children. METHODS:
      Children with asthma who were followed in our pediatric allergy unit were
      consecutively recruited. Asthma severity was graded according to GINA guidelines.
      Children whose asthma was controlled with Step 1 or 2 treatment options formed
      Group 1 (mild asthma), whereas children who needed Step 3, 4, or 5 treatment
      options formed Group 2 (moderate-to-severe asthma). Anthropometric measures
      including height, weight, NC, waist circumference, and hip circumference were
      obtained. RESULTS: A total of 127 children (82 male, 64.6%) with a median age of
      8.3 (6.4-11.3) years were included. Atopy was present in 77 (60.6%) patients. 91
      patients (71.6) were in the mild asthma group. NC of children with severe asthma
      was significantly wider than children with mild asthma (29.0 cm (27.0-32.0) vs.
      28.0 (26.0-30.0), p = 0.019). The prevalence of children with NC higher than 90th
      percentile was also more frequent in children with severe asthma (15 [41.7%] vs.
      21 [23.1%]). Result of multivariable logistic regression analysis revealed that
      presence of NC >90th percentile was associated with severe asthma in children
      (odds ratio; [95% confidence interval] (2.52 [1.05-6.01]; p = 0.038).
      CONCLUSIONS: Neck circumference, which is a simple anthropometric tool, is
      associated with asthma severity in children.

PMID- 25952271
TI  - Quantitative Measurement of Cationic Polymer Vector and Polymer-pDNA Polyplex
      Intercalation into the Cell Plasma Membrane.
AB  - Cationic gene delivery agents (vectors) are important for delivering nucleotides,
      but are also responsible for cytotoxicity. Cationic polymers (L-PEI, jetPEI, and
      G5 PAMAM) at 1* to 100* the concentrations required for translational activity
      (protein expression) induced the same increase in plasma membrane current of HEK
      293A cells (30-50 nA) as measured by whole cell patch-clamp. This indicates
      saturation of the cell membrane by the cationic polymers. The increased currents
      induced by the polymers are not reversible for over 15 min. Irreversibility on
      this time scale is consistent with a polymer-supported pore or carpet model and
      indicates that the cell is unable to clear the polymer from the membrane. For
      polyplexes, although the charge concentration was the same (at N/P ratio of
      10:1), G5 PAMAM and jetPEI polyplexes induced a much larger current increase (40
      50 nA) than L-PEI polyplexes (<20 nA). Both free cationic lipid and lipid
      polyplexes induced a lower increase in current than cationic polymers (<20 nA).
      To quantify the membrane bound material, partition constants were measured for
      both free vectors and polyplexes into the HEK 293A cell membrane using a dye
      influx assay. The partition constants of free vectors increased with charge
      density of the vectors. Polyplex partition constants did not show such a trend.
      The long lasting cell plasma permeability induced by exposure to the polymer
      vectors or the polyplexes provides a plausible mechanism for the toxicity and
      inflammatory response induced by exposure to these materials.

PMID- 25952272
TI  - Tumor Size, an Additional Prognostic Factor to Include in Low-Risk Endometrial
      Cancer: Results of a French Multicenter Study.
AB  - BACKGROUND: Additional tools are needed to improve the selection of women with
      early-stage endometrial cancer (EC) at increased risk of nodal metastases and/or
      recurrence to adapt surgical staging and adjuvant therapies. The aim of this
      study was to assess the impact of EC tumor size on nodal status and recurrence
      free survival (RFS) according to European risk groups for recurrence. METHODS:
      Data of 633 women with early-stage EC who received primary surgical treatment
      between 2001 and 2012 were abstracted from a multicenter database. Optimal tumor
      size cut-offs were determined by a minimal p value approach according to final
      nodal status. Logistic regression was used to determine the impact of defined
      tumor size on nodal involvement, and the Kaplan-Meier method was used to estimate
      the survival distribution. RESULTS: The number of women with final low-,
      intermediate-, and high-risk EC was 302, 204, and 127, respectively. Tumor size
      was correlated with nodal status and RFS in women with low-risk EC, while no
      correlation was found for women with intermediate/high-risk EC. Tumor size >=35
      mm emerged as the optimal threshold for a higher rate of nodal involvement (odds
      ratio 4.318, 95 % CI 1.13-16.51, p = 0.03) and a lower RFS (p = 0.005) in women
      with low-risk EC. CONCLUSION: Tumor size is an independent prognostic factor of
      lymph node involvement in women with low-risk EC and could be a valuable
      additional histological criterion for selecting women at increased risk of lymph
      node metastases to better adapt surgical staging.

PMID- 25952273
TI  - Perceptions of Subjective Burden Among Latino Families Caring for a Loved One
      with Schizophrenia.
AB  - The purpose of this study was to explore perceptions of subjective burden among
      Latino family members providing care for a loved one with schizophrenia. Data
      were collected from outpatient community mental health centers and featured 64
      Latino family members who were primarily Spanish speaking and of Mexican origin.
      We used qualitative methods to examine subjective burden based on an open section
      of the Family Burden Interview Schedule. Five salient themes emerged capturing
      family members' subjective burden experience: (a) interpersonal family
      relationships, (b) emotional and physical health, (c) loss of role expectations,
      (d) religion and spirituality, and (e) stigma. Overall, findings illustrated that
      families perceived numerous challenges in their caregiving. Implications for
      research and practice among Latino family members are discussed. 

PMID- 25952274
TI  - Self-Concept Clarity in Adolescents and Parents: A Six-Wave Longitudinal and
      Multi-Informant Study on Development and Intergenerational Transmission.
AB  - The purpose of this study was twofold: (a) to disentangle patterns of change and
      stability in self-concept clarity (SCC) in adolescents and in their parents and
      (b) to examine processes of intergenerational transmission of SCC in families
      with adolescents. Participants were 497 Dutch families including the father
      (baseline Mage  = 46.74), the mother (baseline Mage  = 44.41), and their
      adolescent child (56.9% males; baseline Mage  = 13.03). Each family member
      completed the SCC scale for six waves, with a one-year interval between each
      wave. Latent growth curve analyses indicated that adolescent boys reported higher
      SCC than girls. Furthermore, fathers and mothers reported higher SCC than their
      children, and it increased over time. Indices of SCC rank-order stability were
      high and increased from T1 to T2, T2 to T3, etc., for each family member,
      especially for adolescents. Multivariate latent growth curve analyses and cross
      lagged models highlighted a unidirectional transmission process, with fathers'
      and mothers' SCC influencing adolescents' SCC. This result was not moderated by
      adolescent gender. These findings indicate that self-concept clarity is
      transmitted from parents to children.

PMID- 25952275
TI  - Kinematical analysis of the trunk, upper limbs and fingers during minimal access
      surgery when using an armrest.
AB  - This study investigated whether using an armrest could reduce the movements of
      the trunk, upper limb and hand of surgeons during simulated minimal access
      surgery. Sixteen surgeons carried out two trials of simulated laparoscopic
      surgery, one using an armrest and the other without. Reflective markers were
      attached on the trunk, upper limbs, fingers, minimal access camera (MAC) and
      scissors, allowing a motion capture system to record the movements. The error
      ratios during operation, subjective opinions and operative durations were
      collected. The results showed that total displacements at the trunk and shoulders
      were reduced by at least 25% when using an armrest compared with not using one;
      error ratios were reduced by 7%; velocity and acceleration in the trunk, shoulder
      and MAC were reduced. After simulated operations, 78% of the participants
      preferred using the armrest. The study indicates that an armrest could improve
      surgical outcomes by reducing trunk movements. PRACTITIONER SUMMARY: An armrest
      may help surgeons to reduce unnecessary movements during operations. The error
      ratios were reduced by 7% when using an armrest compared with no armrest.
      Displacements at the trunk and shoulders were reduced by 25% when using an
      armrest. Seventy-eight per cent of participants preferred to use an armrest after
      the experiment.

PMID- 25952276
TI  - A method of developing and introducing case-based learning to a preclinical
      veterinary curriculum.
AB  - Case-based learning (CBL) has been introduced as part of a major review of the
      veterinary curriculum at the University of Bristol. The initial aim was to
      improve integration between all first year subjects, i.e., basic science
      disciplines (anatomy, physiology, and biochemistry), animal management, and
      professional studies, while highlighting the relevance by providing clinical
      context. The CBL was delivered as whole class sessions in a lecture theatre, as
      small group teaching facilities were not readily available, co-facilitated by two
      to four basic scientists and clinicians. Active learning tasks were included by
      using an audience response system and encouraging discussion. A case template was
      developed in PowerPoint and then populated by basic science and clinical staff in
      an iterative design process. Comments from a student focus group informed the
      design of the case sessions. Feedback collected from students via a survey after
      the first three cases suggested that CBL was well received and assisted students
      in integrating material taught in the first year units and was used to further
      improve the ongoing case design. The project team developed eight cases for Year
      1 and is implementing CBL in various formats throughout the curriculum. There was
      a considerable time commitment in developing each case; however, the use of
      readily available software and the large group format overcame limitations,
      including resourcing small group sessions. This article reports a model that
      could be successfully adapted by other institutions wishing to use CBL to provide
      clinical context and promote integration of the basic sciences.

PMID- 25952277
TI  - The evolution of bariatric surgery.

PMID- 25952278
TI  - Traumatic diaphragmatic injury in the American College of Surgeons National
      Trauma Data Bank: a new examination of a rare diagnosis.
AB  - BACKGROUND: Traumatic diaphragmatic injury (TDI) is a rarely diagnosed injury in
      trauma. Previous studies have been limited in their evaluation of TDI because of
      small population size and center bias. Although injuries may be suspected based
      on penetrating mechanism, blunt injuries may be particularly difficult to detect.
      The American College of Surgeons National Trauma Data Bank is the largest trauma
      database in the United States. We hypothesized that we could identify specific
      injury patterns associated with blunt and penetrating TDIs. METHODS: We examined
      demographics, diagnoses, mechanism of injury, and outcomes for patients with TDI
      in 2012 as this is the largest and most recent dataset available. Comparisons
      were made using chi-square or independent samples t test. RESULTS: There were a
      total of 833,309 encounters in the National Trauma Data Bank in 2012. Three
      thousand eight hundred seventy-three patients had a TDI (.46%). Of those, 1,240
      (33%) patients had a blunt mechanism and 2,543 (67%) had a penetrating mechanism.
      Patients with blunt TDI were older (44 +/- 19 vs 31 +/- 13 years, P < .001), had
      a higher injury severity score (33 +/- 14 vs 24 +/- 15, P < .001), and a higher
      mortality rate (19.8% vs 8.8%, P < .001). Compared with patients with penetrating
      injuries, those with blunt TDI were more likely to have injuries to the thoracic
      aorta (2.9% vs .5%, P < .001), lung (48.7% vs 28.1, P < .001), bladder (5.9% vs
      .7%, P < .001), and spleen (44.8% vs 29.1%, P < .001). Penetrating TDI was
      associated with liver and hollow viscus injuries. CONCLUSIONS: Diaphragmatic
      injury is an uncommon but significant diagnosis in trauma patients. Blunt
      injuries may be more likely to be occult; however, a pattern of associated
      injuries to the aorta, lung, spleen, and bladder should prompt further workup for
      TDI.

PMID- 25952279
TI  - Cognitive and functional patterns of nondemented subjects with equivocal visual
      amyloid PET findings.
AB  - PURPOSE: Despite good to excellent inter-reader agreement in the evaluation of
      amyloid load on PET scans in subjects with Alzheimer's disease, some equivocal
      findings have been reported in the literature. We aimed to describe the clinical
      characteristics of subjects with equivocal PET images. METHODS: Nondemented
      subjects aged 70 years or more were enrolled from the MAPT trial. Cognitive and
      functional assessments were conducted at baseline, at 6 months, and annually for
      3 years. During the follow-up period, 271 subjects had (18)F-AV45 PET scans.
      Images were visually assessed by three observers and classified as positive,
      negative or equivocal (if one observer disagreed). After debate, equivocal images
      were reclassified as positive (EP+) or negative (EP-). Scans were also classified
      by semiautomated quantitative analysis using mean amyloid uptake of cortical
      regions. We evaluated agreement among the observers, and between visual and
      quantitative assessments using kappa coefficients, and compared the clinical
      characteristics of the subjects according to their PET results. RESULTS: In 158
      subjects (58.30 %) the PET scan was negative for amyloid, in 77 (28.41 %) the
      scan was positive and in 36 (13.28 %) the scan was equivocal. Agreement among the
      three observers was excellent (kappa 0.80). Subjects with equivocal images were
      more frequently men (58 % vs. 37 %) and exhibited intermediate scores on
      cognitive and functional scales between those of subjects with positive and
      negative scans. Amyloid load differed between the EP- and negative groups and
      between the EP+ and positive groups after reclassification. CONCLUSION: Equivocal
      amyloid PET images could represent a neuroimaging entity with intermediate
      amyloid load but without a specific neuropsychological pattern. Clinical follow
      up to assess cognitive evolution in subjects with equivocal scans is needed.

PMID- 25952280
TI  - Should PET/CT be implemented in the routine imaging work-up of locally advanced
      head and neck squamous cell carcinoma? A prospective analysis.
AB  - PURPOSE: The objective of this study was to determine the incremental staging
      information provided by positron emission tomography/computed tomography (PET/CT)
      and its impact on management plans in patients with untreated stage III-IV head
      and neck squamous cell carcinoma (HNSCC). METHODS: We prospectively studied,
      between September 2011 and February 2013, 84 consecutive patients [median age
      63.5 years (39-84); 73 men] with histologically confirmed HNSCC. First, based on
      a conventional work-up (physical examination, CT imaging of the head, neck and
      chest), the multidisciplinary Head and Neck Tumour Board documented the TNM stage
      and a management plan for each patient, outlining the modalities to be used,
      including surgery, radiation therapy (RT), chemotherapy or a combination. After
      release of the PET/CT results, new TNM staging and management plans were agreed
      on by the multidisciplinary Tumour Board. Any changes in stage or intended
      management due to the PET/CT findings were then analysed. The impact on patient
      management was classified as: low (treatment modality, delivery and intent
      unchanged), moderate (change within the same treatment modality: type of surgery,
      radiation technique/dose) or high (change in treatment intent and/or treatment
      modality -> curative to palliative, or surgery to chemoradiation or detection of
      unknown primary tumour or a synchronous second primary tumour). TNM stage was
      validated by histopathological analysis, additional imaging or follow-up.
      Accuracy of the conventional and PET/CT-based staging was compared using
      McNemar's test. RESULTS: Conventional and PET/CT stages were discordant in 32/84
      (38 %) cases: the T stage in 2/32 (6.2 %), the N stage in 21/32 (65.7 %) and the
      M stage 9/32 (28.1 %). Patient management was altered in 22/84 (26 %) patients,
      with a moderate impact in 8 (9.5 %) patients and high impact in 14 (16.6 %)
      patients. PET/CT TNM classification was significantly more accurate (92.5 vs 73.7
      %) than conventional staging with a p value < 0.001 (McNemar's test). CONCLUSION:
      PET/CT should be implemented in the routine imaging work-up of stage III-IV
      HNSCC.

PMID- 25952281
TI  - The impact of medical errors on Swiss anaesthesiologists: a cross-sectional
      survey.
AB  - BACKGROUND: Clinicians involved in medical errors can experience significant
      distress. This study aims to examine (1) how medical errors impact
      anaesthesiologists in key work and life domains; (2) anaesthesiologists'
      attitudes regarding support after errors; (3) and which anaesthesiologists are
      most affected by errors. METHODS: This study is a mailed cross-sectional survey
      completed by 281 of the 542 clinically active anaesthesiologists (52% response
      rate) working at Switzerland's five university hospitals between July 2012 and
      April 2013. RESULTS: Respondents reported that errors had negatively affected
      anxiety about future errors (51%), confidence in their ability as a doctor (45%),
      ability to sleep (36%), job satisfaction (32%), and professional reputation (9%).
      Respondents' lives were more likely to be affected as error severity increased.
      Ninety per cent of respondents disagreed that hospitals adequately support them
      in coping with the stress associated with medical errors. Nearly all of the
      respondents (92%) reported being interested in psychological counselling after a
      serious error, but many identified barriers to seeking counselling. However,
      there were significant differences between departments regarding error-related
      stress levels and attitudes about error-related support. Respondents were more
      likely to experience certain distress if they were female, older, had previously
      been involved in a serious error, and were dissatisfied with their last error
      disclosure. CONCLUSION: Medical errors, even minor errors and near misses, can
      have a serious effect on clinicians. Health-care organisations need to do more to
      support clinicians in coping with the stress associated with medical errors.

PMID- 25952283
TI  - An uncommon cause of acral vesiculo-bullous eruption.

PMID- 25952284
TI  - Confluent lesions on left hip of a young woman.

PMID- 25952282
TI  - Three brainstem areas involved in respiratory rhythm generation in bullfrogs.
AB  - For most multiphasic motor patterns, rhythm and pattern are produced by the same
      circuit elements. For respiration, however, these functions have long been
      assumed to occur separately. In frogs, the ventilatory motor pattern produced by
      the isolated brainstem consists of buccal and biphasic lung bursts. Previously,
      two discrete necessary and sufficient sites for lung and buccal bursts were
      identified. Here we identify a third site, the Priming Area, important for and
      having neuronal activity correlated with the first phase of biphasic lung bursts.
      As each site is important for burst generation of a separate phase, we suggest
      each major phase of ventilation is produced by an anatomically distinct part of
      an extensive brainstem network. Embedding of discrete circuit elements producing
      major phases of respiration within an extensive rhythmogenic brainstem network
      may be a shared architectural characteristic of vertebrates. ABSTRACT:
      Ventilation in mammals consists of at least three distinct phases: inspiration,
      post-inspiration and late-expiration. While distinct brainstem rhythm generating
      and pattern forming networks have long been assumed, recent data suggest the
      mammalian brainstem contains two coupled neuronal oscillators: one for
      inspiration and the other for active expiration. However, whether additional
      burst generating ability is required for generating other phases of ventilation
      in mammals is controversial. To investigate brainstem circuit architectures
      capable of producing multiphasic ventilatory rhythms, we utilized the isolated
      frog brainstem. This preparation produces two types of ventilatory motor
      patterns, buccal and lung bursts. Lung bursts can be divided into two phases,
      priming and powerstroke. Previously we identified two putative oscillators, the
      Buccal and Lung Areas. The Lung Area produces the lung powerstroke and the Buccal
      Area produces buccal bursts and - we assumed - the priming phase of lung bursts.
      However, here we identify an additional brainstem region that generates the
      priming phase. This Priming Area extends rostral and caudal of the Lung Area and
      is distinct from the Buccal Area. Using AMPA microinjections and reversible
      synaptic blockade, we demonstrate selective excitation and ablation
      (respectively) of priming phase activity. We also demonstrate that the Priming
      Area contains neurons active selectively during the priming phase. Thus, we
      propose that three distinct neuronal components generate the multiphase
      respiratory motor pattern produced by the frog brainstem: the buccal, priming and
      powerstroke burst generators. This raises the possibility that a similar multi
      burst generator architecture mediates the three distinct phases of ventilation in
      mammals.

PMID- 25952285
TI  - Lichenoid dermatitis caused by thienopyridine derivatives.

PMID- 25952286
TI  - BMP7 and EREG Contribute to the Inductive Potential of Dental Mesenchyme.
AB  - Odontogenesis is accomplished by reciprocal signaling between the epithelial and
      mesenchymal compartments. It is generally accepted that the inductive mesenchyme
      is capable of inducing the odontogenic commitment of both dental and non-dental
      epithelial cells. However, the duration of this signal in the developing dental
      mesenchyme and whether adult dental pulp tissue maintains its inductive
      capability remain unclear. This study investigated the contribution of growth
      factors to regulating the inductive potential of the dental mesenchyme. Human
      oral epithelial cells (OEs) were co-cultured with either human dental
      mesenchymal/papilla cells (FDPCs) or human dental pulp cells (ADPCs) under 2
      dimensional or 3-dimensional conditions. Odontogenic-associated genes and
      proteins were detected by qPCR and immunofluorescence, respectively, and
      significant differences were observed between the two co-culture systems. The
      BMP7 and EREG expression levels in FDPCs were significantly higher than in ADPCs,
      as indicated by human growth factor PCR arrays and immunofluorescence analyses.
      OEs co-cultured with ADPCs supplemented with BMP7 and EREG expressed ameloblastic
      differentiation genes. Our study suggests that BMP7 and EREG expression in late
      bell-stage human dental papilla contributes to the inductive potential of dental
      mesenchyme. Furthermore, adult dental pulp cells supplemented with these two
      growth factors re-established the inductive potential of postnatal dental pulp
      tissue. 

PMID- 25952288
TI  - Mapping brain volumetric abnormalities in never-treated pathological gamblers.
AB  - Several magnetic resonance imaging (MRI) studies to date have investigated brain
      abnormalities in association with the diagnosis of pathological gambling (PG),
      but very few of these have specifically searched for brain volume differences
      between PG patients and healthy volunteers (HV). To investigate brain volume
      differences between PG patients and HV, 30 male never-treated PG patients (DSM-IV
      TR criteria) and 30 closely matched HV without history of psychiatric disorders
      in the past 2 years underwent structural magnetic resonance imaging with a 1.5-T
      instrument. Using Freesurfer software, we performed an exploratory whole-brain
      voxelwise volume comparison between the PG group and the HV group, with false
      discovery rate correction for multiple comparisons (p < 0.05). Using a more
      flexible statistical threshold (p < 0.01, uncorrected for multiple comparisons),
      we also measured absolute and regional volumes of several brain structures
      separately. The voxelwise analysis showed no clusters of significant regional
      differences between the PG and HV groups. The additional analyses of absolute and
      regional brain volumes showed increased absolute global gray matter volumes in PG
      patients relative to the HV group, as well as relatively decreased volumes
      specifically in the left putamen, right thalamus and right hippocampus (corrected
      for total gray matter). Our findings indicate that structural brain abnormalities
      may contribute to the functional changes associated with the symptoms of PG, and
      they highlight the relevance of the brain reward system to the pathophysiology of
      this disorder.

PMID- 25952289
TI  - Exploring the Experiences of Abuse of College Students With Disabilities.
AB  - Intimate partner violence and sexual assault of college students has garnered
      increased attention and publicity. Current studies have focused primarily on
      general campus populations with little to no attention to students with
      disabilities. While studies suggest the rate of abuse of individuals with
      disabilities is similar or higher compared to the general population, there
      remains a lack of focus on this issue. Individuals with disabilities are at
      particularly high risk for abuse, both through typical forms of violence
      (physical, sexual, emotional, and economic) and those that target one's
      disability. In an effort highlight and explore this issue further, an exploratory
      study was conducted to learn the rates of abuse among university students who
      have identified as having a disability. This is a cross-sectional survey of 101
      students of students with disabilities from a large northeastern public
      university. Experiences of abuse were measured through the use of the Abuse
      Assessment Screen- Disability (AAS-D) scale. Students were asked about
      experiences of physical, sexual, psychological, and disability related abuse
      within the last year and help seeking behaviors when an incident of abuse
      occurred. We found that 22 % of participants reported some form of abuse over the
      last and nearly 62% (n= 63) had experienced some form of physical or sexual abuse
      before the age of 17. Those who were abused in the past year, 40% reported little
      or no knowledge of abuse-related resources and only 27% reported the incident.
      Authors discuss implications results have for programs and policies on campus for
      individuals with disabilities.

PMID- 25952290
TI  - Intimate Partner Violence Victims Seeking a Temporary Restraining Order: Social
      Support and Resilience Attenuating Psychological Distress.
AB  - Social support has been found in many studies to be a protective factor for those
      exposed to intimate partner violence (IPV), but personal resilience has received
      far less attention. The present study concerns 136 female IPV victims seeking a
      temporary restraining order (TRO) from a Family Justice Center (FJC). The
      relationships between IPV victimization, social support, resilience, and
      psychological distress were examined. Hierarchical regressions found that both
      perceived social support and self-reported resilience were inversely associated
      with distress symptoms. Higher social support was associated with lower trauma
      symptoms, controlling for abuse history, demographics, and resilience. Higher
      resilience was associated with lower mood symptoms and lower perceived stress,
      controlling for abuse history, demographics, and social support. No significant
      associations were recorded for anger symptoms. These findings suggest that
      fostering resilience can have important health benefits for IPV victims, above
      and beyond the well-known benefits of social support. Ways that resilience might
      be cultivated in this population and other implications for practice are
      discussed.

PMID- 25952291
TI  - Examining the Intersection of Bullying and Physical Relationship Violence Among
      New York City High School Students.
AB  - Research is just beginning to explore the intersection of bullying and
      relationship violence. The relationship between these forms of youth aggression
      has yet to be examined in diverse urban centers, including New York City (NYC).
      This study seeks to identify intersections of joint victimization from bullying
      and electronic bullying (e-bullying) with physical relationship violence (pRV).
      This study examines data from the NYC Youth Risk Behavior Survey (YRBS), a
      representative sample of NYC public high school students, to assess the
      concurrent victimization from bullying at school and e-bullying with pRV,
      operationalized as physical violence by a dating partner in the past 12 months.
      Students who reported being bullied at school and e-bullied had increased odds
      (bullied: OR = 2.5, 95% CI [2.1, 2.9]; e-bullied: OR = 3.0, 95% CI [2.6, 3.5]) of
      also being victimized by pRV compared with those who did not report being bullied
      or e-bullied. In logistic regression models, being bullied at school and being e
      bullied remained significant predictors of students' odds of reporting pRV
      (bullied: AOR = 2.6, 95% CI [2.2, 3.1]; e-bullied: AOR = 3.0, 95% CI [2.5, 3.6])
      while controlling for race, gender, sexual orientation, and age. This research is
      the first to assess the intersection of victimization from bullying and e
      bullying with pRV in a large, diverse, random sample of urban high school
      students. In this sample, students who report being bullied or e-bullied are more
      likely also to report pRV than students who have not been bullied or e-bullied.
      This research has potential implications for educators, adolescent health and
      social service providers, and policy makers to tailor programs and enact policies
      that jointly address bullying and pRV. Future studies are needed to
      longitudinally assess both victimization from and perpetration of bullying and
      pRV.

PMID- 25952292
TI  - 5th World Congress on ADHD: From Child to Adult Disorder 28-31 May 2015 . Glasgow
      . Scotland Editors: Manfred Gerlach, Wurzburg, Germany Peter Riederer, Wurzburg,
      Germany Luis A. Rohde, Porto Alegre, Brazil Andreas Warnke, Wurzburg, Germany.

PMID- 25952294
TI  - Tribological characteristics of enamel-dental material contacts investigated in
      vitro.
AB  - PURPOSE: The aim of this study was to investigate wear and friction behaviour of
      tooth enamel against selected dental restorative materials. METHODS: The
      experimental material was obtained under simulated mastication, during which
      human tooth enamel was sub- jected to friction and wear in contact with composite
      dental materials: Estelite Sigma and FulFil Extra. RESULTS: The results have
      shown that the enamel's resistance to tribological wear is significantly higher
      than the resistance of the dental materials tested. The microscopic observations
      of the sample surfaces subsequent to the tribological research as well as the
      analysis of the chemical composition of the surface layer confirm the existence
      of diverse tribological wear mechanisms dependent on the type of dental materials
      used. CONCLUSIONS: Composite materials such as Estellite Sigma and FulFil Extra
      are characterized by greater resistance to wear and are less destructive to
      enamel than the material investigated by the authors earlier. It has also been
      stated that the spherical shape of the filler particles (Estellite Sigma) has a
      beneficial effect in reducing enamel wear.

PMID- 25952293
TI  - Hepatic fat quantification using the proton density fat fraction (PDFF): utility
      of free-drawn-PDFF with a large coverage area.
AB  - PURPOSE: To evaluate the diagnostic performance of magnetic resonance imaging
      estimated proton density fat fraction (MRI-PDFF) using a free-drawn region-of
      interest (ROI) measurement of hepatic fat deposition compared to MR spectroscopy
      (MRS) as the reference standard. MATERIALS AND METHODS: A total of 156 patients
      underwent 3T MR imaging with a multi-step adaptive fitting approach, multi-echo
      volume interpolated breath-hold examination (VIBE) acquisition and single-voxel
      high-speed T2-corrected multiple-echo (1)H-MR spectroscopy (SVS). Seven ROI
      measurements were performed in each segment of the fat percentage maps
      ("segmental-PDFF"). Three ROIs were placed at the same level as the SVS ("VOI
      PDFF"). Free-hand-drawn ROIs were placed at three different levels along the
      entire liver ("free-drawn-PDFF") and separately along the right and left lobes
      ("free-drawn-PDFF-2"). RESULTS: A strong correlation was found between VOI-PDFF
      and SVS (r = 0.977). The right lobe had greater fat content than the left lobe (p
      < 0.001). After image analysis, 54 and 46 patients were classified as having
      steatosis using SVS and free-drawn-PDFF as a reference standard, respectively.
      The diagnostic performance of free-drawn-PDFF was significantly different from
      SVS (p < 0.05). CONCLUSION: Free-drawn-PDFF provides accurate and generalized
      information regarding hepatic fat deposition. It is a useful method, particularly
      if fat deposition is heterogeneous, and should be considered as a new reference
      standard.

PMID- 25952296
TI  - Thermal denaturation behavior of collagen fibrils in wet and dry environment.
AB  - We have developed a new minimally invasive technique--integrated low-level energy
      adhesion technique (ILEAT)--which uses heat, pressure, and low-frequency
      vibrations for binding living tissues. Because the adhesion mechanism of the
      living tissues is not fully understood, we investigated the effect of thermal
      energy on the collagen structure in living tissues using ILEAT. To study the
      effect of thermal energy and heating time on the structure of the collagen
      fibril, samples were divided in two categories-wet and dry. Further, atomic force
      microscopy was used to analyze the collagen fibril structure before and after
      heating. Results showed that collagen fibrils in water denatured after 1 minute
      at temperatures higher than 80  degrees C, while partial denaturation was
      observed at temperatures of 80  degrees C and a heating time of 1 min.
      Furthermore, complete denaturation was achieved after 90 min, suggesting that the
      denaturation rate is temperature and time dependent. Moreover, the collagen
      fibrils in dry condition maintained their native structure even after being
      heated to 120  degrees C for 90 min in the absence of water, which specifically
      suppressed denaturation. However, partial denaturation of collagen fibrils could
      not be prevented, because this determines the adhesion between the collagen
      molecules, and stabilizes tissue bonding.

PMID- 25952295
TI  - In geriatric patients, delirium symptoms are related to the anticholinergic
      burden.
AB  - AIM: Anticholinergic drugs are widely prescribed for elderly patients and could
      induce several neuropsychological disorders, especially delirium. The aim of the
      present study was to evaluate the relationship between anticholinergic burden and
      delirium symptoms. METHODS: A total of 102 patients aged over 75 years (86.3 +/-
      5.8 years, 53 women and 49 men) hospitalized in a geriatric medicine department
      were included in this prospective study. Anticholinergic burden was assessed by
      classifying drug use into three levels (low, medium or high). An overall,
      weighted score was established. Delirium symptoms were measured with the
      Confusion Assessment Method on days 1, 3, 5, 8, 15 and 21. Covariates studied
      were comorbidities (Charlson), health status, activities of daily living,
      nutrition (albumin), cognition, length of stay and mortality. RESULTS: A total of
      51.6% of the patients were taking anticholinergic drugs at home (2.13 +/- 1.34).
      Length of stay was 14.5 +/- 9.9 days. Prevalence of delirium symptoms ranged on
      days between 34.8 and 60%. Anticholinergic burden was correlated with the
      appearance of delirium symptoms. Delirium symptoms were associated with greater
      mortality (16.1 and 3.7 % in patients with and without delirium symptoms; P =
      0.049), a longer hospital stay (18.09 +/- 11.34 vs 11.75 +/- 7.80 days, P =
      0.001), greater dependence on discharge (activities of daily living score: 1.57
      +/- 1.56 vs 3.41 +/- 1.45, P < 0.0001) and worse health status on discharge (5.3
      +/- 2.7 vs 7.0 +/- 1.7, P = 0.0008). CONCLUSION: Anticholinergic burden appears
      as a risk factor for both delirium symptoms and mortality. Prevention of delirium
      symptoms requires its reduction.

PMID- 25952297
TI  - Expression of the vault RNA protects cells from undergoing apoptosis.
AB  - Non-protein-coding RNAs are a functionally versatile class of transcripts
      exerting their biological roles on the RNA level. Recently, we demonstrated that
      the vault complex-associated RNAs (vtRNAs) are significantly upregulated in
      Epstein-Barr virus (EBV)-infected human B cells. Very little is known about the
      function(s) of the vtRNAs or the vault complex. Here, we individually express
      latent EBV-encoded proteins in B cells and identify the latent membrane protein 1
      (LMP1) as trigger for vtRNA upregulation. Ectopic expression of vtRNA1-1, but not
      of the other vtRNA paralogues, results in an improved viral establishment and
      reduced apoptosis, a function located in the central domain of vtRNA1-1.
      Knockdown of the major vault protein has no effect on these phenotypes revealing
      that vtRNA1-1 and not the vault complex contributes to general cell death
      resistance. This study describes a NF-kappaB-mediated role of the non-coding
      vtRNA1-1 in inhibiting both the extrinsic and intrinsic apoptotic pathways. 

PMID- 25952298
TI  - Telomere length and telomerase expression in pituitary tumors.
AB  - PURPOSE: Telomere dysfunction and telomerase activation underlie cancer
      transformation. This study aims to investigate the contribution of telomere
      biology to pituitary tumor behavior. SUBJECTS AND METHODS: Samples from 50
      patients with pituitary tumors (11 ACTH-secreting, 18 GH-secreting, and 21 non
      secreting tumors) and 7 subjects without pituitary lesions were collected. The
      expressions of telomerase essential components TERT and TERC and tumor telomere
      content were measured by quantitative PCR techniques. RESULTS: Telomerase (TERT)
      expression was detected in 36% of tumors. No correlation was observed between
      TERT and TERC expression level and tumor size in any tumor type. There was no
      association between gene expression and clinical findings. Telomere content (T/S
      ratio) was similar between pituitary adenomas (0.39 +/- 0.16) and normal
      pituitaries (0.47 +/- 0.12; p = 0.24) and also was between the different adenoma
      types: ACTH-secreting (0.43 +/- 0.08), GH-secreting (0.31 +/- 0.12), and non
      secreting (0.42 +/- 0.20; p = 0.10) tumors. CONCLUSIONS: The telomere content and
      expression of telomerase components are comparable between normal pituitary
      glands and tumor tissues, suggesting that telomere biology does not play an
      important role in pituitary tumor development.

PMID- 25952300
TI  - Association of metabolic syndrome components with insulin resistance in normal
      weight population: the Qazvin Metabolic Diseases study.
AB  - PURPOSE: Metabolically obese but normal weight (MONW) is associated with higher
      risk of type 2 diabetes, dyslipidemia, and hypertension. The aim of this study
      was to evaluate the association of metabolic syndrome components with MONW in
      each sex in Iranian population. METHODS: This cross-sectional study was performed
      on 417 normal weight subjects in Qazvin, Iran between September 2010 and April
      2011. MONW was defined by insulin resistance (IR) using the homeostatic model
      assessment (HOMA). Cut off point for IR was defined as the lower limit of top
      quintile of HOMA-IR values in normal weight population without any metabolic risk
      factors. Data were analyzed using T test, Mann-Whitney U test, and multi-variant
      logistic regression analysis. RESULTS: Of 417 subjects, 44.3 % were female. The
      prevalence of MONW was 33.8 % in men and 39.8 % in women. Triglycerides levels
      were significantly higher in both men and women with MONW. Waist circumference
      was significantly higher in men with MONW, while high-density lipoprotein
      cholesterol levels were significantly lower in women with MONW. In logistic
      regression analysis, hypertriglyceridemia in women (OR 3.398; 95 % CI 1.306
      8.846) and waist circumference (per 5 cm increment) in men (OR 1.653; 95 % CI
      1.279-2.136) had independent association with MONW. CONCLUSION: Association of
      metabolic syndrome components with MONW is different in men and women. Waist
      circumference had an independent association with IR in men but not in women. IR
      and its complications should be considered in lean women with
      hypertriglyceridemia.

PMID- 25952299
TI  - Vitamin D and bone mineral density changes in postmenopausal women treated with
      strontium ranelate.
AB  - OBJECTIVE: Vitamin D deficiency is widespread and often reported in subjects
      treated for osteoporosis. Optimal vitamin D repletion was previously shown to
      maximize the efficacy of anti-resorptive agents. To date, no information exists
      about the role of vitamin D in the response to strontium ranelate (SrR)
      treatment. The aim of our study was to investigate the BMD response to SrR in
      accordance with change of vitamin D status. METHODS: A retrospective analysis of
      108 women receiving SrR for postmenopausal osteoporosis was carried out. Women
      were treated with SrR (2 g/day), with cholecalciferol (25,000 IU biweekly) and
      calcium carbonate as appropriate. Lumbar spine and femoral neck BMD, bone
      formation markers (BGP, ALP), resorption marker (OH-PRO) and serum 25(OH)D were
      measured at baseline after 18-months. All participants were divided into two
      groups according to the median variation of 25(OH)D over the observation period.
      RESULTS: SrR was associated with improvement of BMD at lumbar spine (p < 0.0001)
      and to a non significant variation at femoral neck (p = 0.2). Only subjects with
      Delta25(OH)D > 6.14 %, reported a significant BMD gain at femoral neck (p =
      0.03). Change of BMD at femoral neck was positively associated with modification
      of ALP (r = 0.28, p = 0.01). This association was not maintained when considering
      only women with Delta25(OH)D < 6.14 % (r = 0.28, p = 0.09). At a multiple
      regression analysis, ALP change was the only predictor of femoral neck BMD
      modification (beta 0.13; SE 0.05; p = 0.01). CONCLUSION: Improvement of vitamin D
      status was associated with enhancement of BMD response to SrR in women with
      postmenopausal osteoporosis, in particular, at femoral neck.

PMID- 25952301
TI  - The effect of age-at-testing on verbal memory among children following severe
      traumatic brain injury.
AB  - Memory deficits are a common sequelae following childhood traumatic brain injury
      (TBI), which often have serious implications on age-related academic skills. The
      current study examined verbal memory performance using the Rey Auditory Verbal
      Learning Test (RAVLT) in a pediatric TBI sample. Verbal memory abilities as well
      as the effect of age at-testing on performance were examined. A sample of 67
      children following severe TBI (age average = 12.3 +/- 2.74) and 67 matched
      controls were evaluated using the RAVLT. Age effect at assessment was examined
      using two age groups: above and below 12 years of age during evaluation.
      Differences between groups were examined via the 9 RAVLT learning trials and the
      7 composite scores conducted out of them. Children following TBI recalled
      significantly less words than controls on all RAVLT trials and had significantly
      lower scores on all composite scores. However, all of these scores fell within
      the low average range. Further analysis revealed significantly lower than average
      performance among the older children (above 12 years), while scores of the
      younger children following TBI fell within average limits. To conclude, verbal
      memory deficits among children following severe TBI demonstrate an age-at-testing
      effect with more prominent problems occurring above 12 years at the time of
      evaluation. Yet, age-appropriate performance among children below 12 years of age
      may not accurately describe memory abilities at younger ages following TBI. It is
      therefore recommended that clinicians address child's age at testing and avoid
      using a single test as an indicator of verbal memory functioning post TBI. 

PMID- 25952302
TI  - Psychoactive pharmaceuticals as environmental contaminants may disrupt highly
      inter-connected nodes in an Autism-associated protein-protein interaction
      network.
AB  - BACKGROUND: Most cases of idiopathic autism spectrum disorder (ASD) likely result
      from unknown environmental triggers in genetically susceptible individuals. These
      triggers may include maternal exposure of a fetus to minute concentrations of
      pharmaceuticals, such as carbamazepine (CBZ), venlafaxine (VNX) and fluoxetine
      (FLX). Unmetabolized pharmaceuticals reach drinking water through a variety of
      routes, including ineffectively treated sewage. Previous studies in our
      laboratory examined the extent to which gene sets were enriched in minnow brains
      treated with pharmaceuticals. Here, we tested the hypothesis that genes in fish
      brains and human cell cultures, significantly enriched by pharmaceuticals, would
      have distinct characteristics in an ASD-associated protein interaction network.
      We accomplished this by comparing these groups using 10 network indices. RESULTS:
      A network of 7212 proteins and 33,461 interactions was generated. We found that
      network characteristics for enriched gene sets for particular pharmaceuticals
      were distinct from each other, and were different from non-enriched ASD gene
      sets. In particular, genes in fish brains, enriched by CBZ and VNX 1) had higher
      network importance than that in the overall network, and those enriched by FLX,
      and 2) were distinct from FLX and non-enriched ASD genes in multivariate network
      space. Similarly, genes in human cell cultures enriched by pharmaceutical
      mixtures (at environmental concentrations) and valproate (at clinical dosages)
      had similar network signatures, and had greater network importance than genes in
      the overall ASD network. CONCLUSIONS: The results indicate that important gene
      sets in the ASD network are particularly susceptible to perturbation by
      pharmaceuticals at environmental concentrations.

PMID- 25952303
TI  - [Imaging for dementia].

PMID- 25952304
TI  - [Acute sports injuries and chronic overuse stress damage to the forefoot and
      midfoot].
AB  - Sports injuries of the foot can occur as sequelae of acute trauma or chronic
      overuse. Besides clinical examination, imaging plays a major role in the
      detection of structural abnormalities and the differential diagnostics. This
      article reviews the most important sports-related soft tissue and bone
      pathologies of the forefoot and midfoot together with their typical findings on
      radiography, ultrasound, computed tomography (CT) and magnetic resonance imaging
      (MRI). 

PMID- 25952306
TI  - Mucoadhesive nanoparticles: a new perspective for fish drug application.

PMID- 25952305
TI  - Molecular Diversity and Associated Phenotypic Spectrum of Germline CBL Mutations.
AB  - Noonan syndrome (NS) is a relatively common developmental disorder with a
      pleomorphic phenotype. Mutations causing NS alter genes encoding proteins
      involved in the RAS-MAPK pathway. We and others identified Casitas B-lineage
      lymphoma proto-oncogene (CBL), which encodes an E3-ubiquitin ligase acting as a
      tumor suppressor in myeloid malignancies, as a disease gene underlying a
      condition clinically related to NS. Here, we further explored the spectrum of
      germline CBL mutations and their associated phenotype. CBL mutation scanning
      performed on 349 affected subjects with features overlapping NS and no mutation
      in NS genes allowed the identification of five different variants with
      pathological significance. Among them, two splice-site changes, one in-frame
      deletion, and one missense mutation affected the RING domain and/or the adjacent
      linker region, overlapping cancer-associated defects. A novel nonsense mutation
      generating a v-Cbl-like protein able to enhance signal flow through RAS was also
      identified. Genotype-phenotype correlation analysis performed on available
      records indicated that germline CBL mutations cause a variable phenotype
      characterized by a relatively high frequency of neurological features,
      predisposition to juvenile myelomonocytic leukemia, and low prevalence of cardiac
      defects, reduced growth, and cryptorchidism. Finally, we excluded a major
      contribution of two additional members of the CBL family, CBLB and CBLC, to NS
      and related disorders. 

PMID- 25952307
TI  - Formation of hollow silica nanospheres by reverse microemulsion.
AB  - Uniform hollow silica nanospheres (HSNs) synthesized with reverse microemulsion
      have great application potential as nanoreactors because enzymes or nanocatalysts
      can be easily encapsulated de novo in synthesis. Water-in-oil (w/o) reverse
      microemulsions comprising the polymeric surfactant polyoxyethylene (5)
      isooctylphenyl ether (Igepal CA-520), ammonia and water in a continuous oil phase
      (alkanes) coalesce into size-tunable silica nanoparticles via diffusion
      aggregation after the introduction of silica precursors. Here, we elucidate in
      detail the growth mechanism for silica nanoparticles via nucleation of ammonium
      catalyzed silica oligomers from tetraethylorthosilicate (TEOS) and nanoporous
      aminopropyltrimethoxy silane (APTS) in the reverse microemulsion system. The
      formation pathway was studied in situ with small-angle X-ray scattering (SAXS).
      We find a four-stage process showing a sigmoidal growth behavior in time with a
      crossover from the induction period, early nucleation stage, coalescence growth
      and a final slowing down of growth. Various characterizations (TEM, N2 isotherm,
      dynamic light scattering, zeta potential, NMR, elemental analysis) reveal the
      diameters, scattering length density (SLD), mesoporosity, surface potentials and
      chemical compositions of the HSNs. Oil phases of alkanes with different alkyl
      chains are systematically employed to tune the sizes of HSNs by varying oil molar
      volumes, co-solvent amounts or surfactant mixture ratios. Silica condensation is
      incomplete in the core region, with the silica source of TEOS and APTS leading to
      the hollow silica nanosphere after etching with warm water. 

PMID- 25952308
TI  - Hidradenitis Suppurativa in Patients With Inflammatory Bowel Disease: A
      Population-Based Cohort Study in Olmsted County, Minnesota.
AB  - BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) may be at
      higher risk for hidradenitis suppurativa (HS). We studied the risk and clinical
      characteristics of HS in a population-based cohort of patients with IBD. METHODS:
      We identified all cases of HS (confirmed by biopsy and/or dermatologic
      evaluation) in a population-based inception cohort of Olmsted County, Minnesota,
      residents diagnosed with IBD between 1970 and 2004 and followed up through August
      2013. We estimated the incidence rate ratio of HS in patients with IBD compared
      with the general population, and described the clinical characteristics, risk
      factors, and management of HS. RESULTS: In 679 IBD patients followed up over a
      median of 19.8 years, we identified 8 patients with HS (mean age, 44.4 +/- 8.3 y;
      7 women; 6 obese). Compared with the general population, the incidence rate ratio
      of HS in IBD was 8.9 (95% confidence interval, 3.6-17.5). The 10- and 30-year
      cumulative incidence of HS was 0.85% and 1.55%, respectively. Five patients had
      Crohn's disease, 4 of whom had perianal disease; of 3 patients with ulcerative
      colitis, 2 had undergone ileal pouch-anal anastomosis. Axillae, groin, and thighs
      were the most common sites of involvement. Six patients had Hurley stage 2
      disease (recurrent abscesses with sinus tracts and scarring, involving widely
      separated areas), and required a combination of antibiotics and surgery; none of
      the patients were treated with anti-tumor necrosis factor-alpha agents.
      CONCLUSIONS: In this population-based study, patients with IBD were approximately
      9 times more likely to develop HS than the general population, with a female
      predisposition.

PMID- 25952310
TI  - Expanding the Scope of Integrated Behavioral Health Care for Patients With
      Hepatitis C Virus.

PMID- 25952309
TI  - White-Light or Narrow-Band Imaging Colonoscopy in Surveillance of Ulcerative
      Colitis: A Prospective Multicenter Study.
AB  - BACKGROUND & AIMS: Early detection of neoplastic lesions is essential in patients
      with long-standing ulcerative colitis but the best technique of colonoscopy still
      is controversial. METHODS: We performed a prospective multicenter study in
      patients with long-standing ulcerative colitis. Two colonoscopies were performed
      in each patient within 3 weeks to 3 months. In white-light (WL) colonoscopy,
      stepwise random biopsy specimens (4 biopsy specimens every 10 cm), segmental
      random biopsies (2 biopsy specimens in 5 segments), and targeted biopsy specimens
      were taken. In NBI colonoscopy, segmental and targeted biopsy specimens were
      taken. The sequence of WL and NBI colonoscopy was randomized. RESULTS: In 36 of
      159 patients enrolled (22.6%), 54 lesions with intraepithelial neoplasia (IN)
      were found (51 low-grade, 3 high-grade). In WL colonoscopy we found 11 IN in
      stepwise biopsy specimens, 4 in segmental biopsy specimens, and 15 in targeted
      biopsy specimens. In NBI colonoscopy 7 IN were detected in segmental biopsy
      specimens and 24 IN were detected in targeted biopsy specimens. Almost all IN
      were found with one technique alone (kappa value of WL vs NBI, -0.86; P < .001).
      Statistically equivalent numbers of IN were found in NBI colonoscopy with
      targeted and segmental biopsy specimens as in WL colonoscopy with targeted and
      stepwise biopsy specimens, but with fewer biopsy specimens (11.9 vs 38.6 biopsy
      specimens, respectively; P < .001), and less withdrawal time was necessary (23 vs
      13 min, respectively; P < .001). CONCLUSIONS: Stepwise biopsy specimens are
      indispensable in WL colonoscopy. The combination of targeted and segmental biopsy
      specimens in the NBI technique is as sensitive as targeted together with stepwise
      biopsy specimens in WL colonoscopy, but requires fewer biopsy specimens and less
      time. The highest sensitivity should be reached by combining the WL and NBI
      techniques by switching between the modes.

PMID- 25952311
TI  - Pregnancy is a Risk Factor for Pancreatitis After Endoscopic Retrograde
      Cholangiopancreatography in a National Cohort Study.
AB  - BACKGROUND & AIMS: There are limited data on the safety of endoscopic retrograde
      cholangiopancreatography (ERCP) during pregnancy, only data from observational
      series (approximately 350 cases) have been published. We aimed to evaluate the
      safety of ERCP in pregnant women by evaluating a large nationwide database.
      METHODS: We performed a retrospective matched-cohort study, collecting data from
      the National Inpatient Sample from 2008 through 2009. We compared data from
      pregnant women who underwent ERCP (n = 907) with those from nonpregnant women who
      underwent ERCP (controls, n = 2721). Complications related to ERCP were measured
      against the matched controls. Obstetric and fetal complications were measured
      against the national average of all obstetric admissions. RESULTS: ERCP
      associated complications of perforation, infection, and bleeding were infrequent
      in both cohorts (P > .05). Post-ERCP pancreatitis (PEP) occurred in 12% of
      pregnant women and in 5% of controls (P < .001). There was a significantly lower
      rate of PEP in teaching hospitals (9.6%) than in nonteaching hospitals (14.6%; P
      < .001). The adjusted odds ratio for developing PEP among pregnant women vs
      controls was 2.8 (95% confidence interval [CI], 2.1-3.8). This risk of PEP was
      higher among nonteaching hospitals (adjusted odds ratio, 3.5; 95% CI, 2.3-5.2)
      than teaching hospitals (adjusted odds ratio, 2.5; 95% CI, 1.6-3.9). CONCLUSIONS:
      Pregnancy is an independent risk factor for PEP; PEP and PEP among pregnant women
      are each more prevalent in community hospitals than teaching centers. Proper
      precautions therefore should be considered for pregnant women undergoing ERCP,
      including transfer to a tertiary care center if appropriate.

PMID- 25952312
TI  - The non-aqueous fluorolytic sol-gel synthesis of nanoscaled metal fluorides.
AB  - This review article focuses on the mechanism of the non-aqueous fluorolytic sol
      gel-synthesis of nanoscopic metal fluorides and hydroxide fluorides. Based on MAS
      NMR, XRD, WAXS and SAXS investigations in combination with computational
      calculations, it is shown that a stepwise replacement of alkoxide by F-ions takes
      place resulting in the formation of a large variety of metal alkoxide fluoride
      clusters, some of them being isolated and structurally characterised. It is shown
      that these nanoscopic metal fluorides obtained via this new synthesis approach
      exhibit distinctly different properties compared with their classically prepared
      homologues. Thus, extremely strong solid Lewis acids are available which give
      access to new catalytic reactions with sometimes unexpectedly high conversion
      degrees and selectivity. Even more interestingly, metal hydroxide fluorides can
      be obtained via this synthesis route that are not accessible via any other
      approach for which the hydroxide to fluoride ratios can be adjusted over a wide
      range. Optically fully transparent sols obtained in this way can be used for the
      first time to manufacture antireflective coatings, corundum ceramics with
      drastically improved properties as well as novel metal fluoride based organic
      inorganic composites. The properties of these new fluoride based materials are
      presented and discussed in context with the above mentioned new fields of
      application. 

PMID- 25952313
TI  - Disentangling longitudinal relations between physical activity, work-related
      fatigue, and task demands.
AB  - PURPOSE: This longitudinal study examined 'normal', 'reversed', and 'reciprocal'
      relationships between (1) physical activity and work-related fatigue; and (2)
      physical activity and task demands. Furthermore, the effects of across-time
      change in meaningful physical activity groups on levels of employees' work
      related fatigue and task demands were studied. These groups were based on
      employees' compliance with the international physical activity norm. METHODS: Two
      waves with a one-year time lag of a national representative survey on the quality
      of work, health, and well-being among Dutch employees were used (N = 2275).
      Longitudinal effects were tested using Structural Equation Modelling. Meaningful
      physical activity groups were compared using group-by-time analysis of
      covariance. RESULTS: Support was found for reciprocal relations between physical
      activity and work-related fatigue. It was found that an increase in physical
      activity is associated with a decrease in work-related fatigue over time and that
      an increase in work-related fatigue is associated with a decrease in physical
      activity over time. No significant longitudinal relations were found between
      physical activity and task demands. Employees whose compliance with the physical
      activity norm changed over time showed fairly stable levels of work-related
      fatigue and task demands. CONCLUSIONS: The current findings provide evidence for
      the potential role of physical activity in the prevention and reduction in work
      related fatigue. However, results also indicate that fatigued workers, who would
      benefit most from physical activity, are less physically active. Our results
      further indicate that relying on changes in compliance to the physical activity
      norm may not be the most suitable way to examine changes in work-related fatigue.

PMID- 25952314
TI  - Effects of profession on urinary PAH metabolite levels in the US population.
AB  - PURPOSE: Although exposure to polycyclic aromatic hydrocarbons (PAHs) is common
      in both environmental and occupational settings, few studies have compared PAH
      exposure among people with different professions. The purpose of this study was
      to investigate the variations in recent PAH exposure among different occupational
      groups over time using national representative samples. METHOD: The study
      population consisted of 4162 participants from the 2001 to 2008 National Health
      and Nutrition Examination Survey, who had both urinary PAH metabolites and
      occupational information. Four corresponding monohydroxy-PAH urine metabolites:
      naphthalene (NAP), fluorene (FLUO), phenanthrene (PHEN), and pyrene (PYR) among
      seven broad occupational groups were analyzed using weighted linear regression
      models, adjusting for creatinine levels, sociodemographic factors, smoking
      status, and sampling season. RESULTS: The overall geometric mean concentrations
      of NAP, FLUO, PHEN, and PYR were 6927, 477, 335, and 87 ng/L, respectively. All
      four PAH metabolites were elevated in the "extractive, construction, and repair
      (ECR)" group, with 21-42 % higher concentrations than those in the reference
      group of "management." Similar trends were seen in the "operators, fabricators,
      and laborers (OFL)" group for FLUO, PHEN, and PYR. In addition, both "service"
      and "support" groups had elevated FLUO. Significant (p < 0.001) upward temporal
      trends were seen in NAP and PYR, with an approximately 6-17 % annual increase,
      and FLUO and PHEN remained relatively stable. Race and socioeconomic status show
      independent effects on PAH exposure. CONCLUSIONS: Heterogeneous distributions of
      urinary PAH metabolites among people with different job categories exist at the
      population level. The upward temporal trends in NAP and PYR warrant reduction in
      PAH exposure, especially among those with OFL and ECR occupations.

PMID- 25952315
TI  - Investigating the effect of thermal stress on nerve action potential using the
      soliton model.
AB  - The thermal mechanism of acoustic modulation of the reversible electrical
      activities of peripheral nerves is investigated using the soliton model, and a
      numerical solution is presented for its non-homogenous version. Our results
      indicate that heating a small segment of the nerve will increase the action
      potential conduction velocity and decrease its amplitude. Moreover, cooling the
      nerve will have the reverse effects, and cooling to temperatures below the nerve
      melting point can reflect back a significant portion of the action potentials.
      These results are consistent with the theory of the soliton model, as well as
      with the experimental findings. Although there exists a discrepancy between the
      results of the soliton model and experimental pulse amplitude data, from the free
      energy point of view, the experiments are compatible with Heimburg and Jackson
      theory. We conclude that the presented model accompanied by the free energy view
      is capable of simulating the effects of thermal energy on nerve function. One
      potential application of the developed theoretical model will be investigation of
      the reversible and irreversible effects of thermal energy induced by various
      energy modalities, including therapeutic ultrasound, on nerve function. 

PMID- 25952316
TI  - Successful capture of Toxocara canis larva antigens from human serum samples.
AB  - BACKGROUND: Toxocara canis is a nematode that parasitizes dogs, while humans are
      paratenic hosts. When humans are infected the migrating larvae damage the liver,
      lungs and even the nervous system. Larva migrans diagnosis is based on
      immunological techniques; however, the commercial immunodiagnostic kits detect
      anti-T. canis antibodies which may cross-react with other parasites, mainly
      nematodes with extra-intestinal migration. Moreover, antibodies do not
      necessarily reflect an active infection; so detection and quantification of
      circulating antigens may provide appropriate and timely information for
      treatment, which prevents irreversible damage. Here we report the standardization
      of a monoclonal antibody based antigen capture ELISA to diagnose human
      toxocariasis without cross-reaction. METHODS: We developed anti-T. canis
      polyclonal antibodies in rabbits and a monoclonal antibody in mouse which did not
      cross-react with 15 antigens from several parasites. The sandwich ELISA
      standardization was performed using sera from mice experimentally infected. We
      tested the method using 29 positive and 58 negative human sera previously
      typified with a commercial kit, which detects antibodies. RESULTS: Only 5.0
      MUg/mL and 10 MUg/mL polyclonal antibodies and monoclonal antibody, respectively,
      were needed in the sandwich ELISA standardization, detecting since 440 pg/mL
      larva antigens. Nine out of 29 antibody-positive sera were also positive for
      antigens and no false positive were found. Taking the antibody kit as the
      reference standard, the sensibility and specificity of the antigen test were 31%
      and 100%, respectively. CONCLUSIONS: With these tools we established a detection
      threshold as low as 440 pg/mL antigen. Monoclonal antibody is specific, and did
      not cross-react with antigens from other parasites. Detection of circulating
      antigens helps provide appropriate and timely treatment and prevents irreversible
      damage.

PMID- 25952317
TI  - SWITCH: A Randomised, Sequential, Open-label Study to Evaluate the Efficacy and
      Safety of Sorafenib-sunitinib Versus Sunitinib-sorafenib in the Treatment of
      Metastatic Renal Cell Cancer.
AB  - BACKGROUND: Understanding how to sequence targeted therapies for metastatic renal
      cell carcinoma (mRCC) is important for maximisation of clinical benefit.
      OBJECTIVES: To prospectively evaluate sequential use of the multikinase
      inhibitors sorafenib followed by sunitinib (So-Su) versus sunitinib followed by
      sorafenib (Su-So) in patients with mRCC. DESIGN, SETTING, AND PARTICIPANTS: The
      multicentre, randomised, open-label, phase 3 SWITCH study assessed So-Su versus
      Su-So in patients with mRCC without prior systemic therapy, and stratified by
      Memorial Sloan Kettering Cancer Center risk score (favourable or intermediate).
      INTERVENTION: Patients were randomised to sorafenib 400mg twice daily followed,
      on progression or intolerable toxicity, by sunitinib 50mg once daily (4 wk on, 2
      wk off) (So-Su), or vice versa (Su-So). OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: The primary endpoint was improvement in progression-free survival (PFS)
      with So-Su versus Su-So, assessed from randomisation to progression or death
      during second-line therapy. Secondary endpoints included overall survival (OS)
      and safety. RESULTS AND LIMITATIONS: In total, 365 patients were randomised (So
      Su, n=182; Su-So, n=183). There was no significant difference in total PFS
      between So-Su and Su-So (median 12.5 vs 14.9 mo; hazard ratio [HR] 1.01; 90%
      confidence interval [CI] 0.81-1.27; p=0.5 for superiority). OS was similar for So
      Su and Su-So (median 31.5 and 30.2 mo; HR 1.00, 90% CI 0.77-1.30; p=0.5 for
      superiority). More So-Su patients than Su-So patients reached protocol-defined
      second-line therapy (57% vs 42%). Overall, adverse event rates were generally
      similar between the treatment arms. The most frequent any-grade treatment
      emergent first-line adverse events were diarrhoea (54%) and hand-foot skin
      reaction (39%) for sorafenib; and diarrhoea (40%) and fatigue (40%) for
      sunitinib. CONCLUSIONS: Total PFS was not superior with So-Su versus Su-So. These
      results demonstrate that sorafenib followed by sunitinib and vice versa provide
      similar clinical benefit in mRCC. PATIENT SUMMARY: We investigated if total
      progression-free survival (PFS) is improved in patients with advanced/metastatic
      kidney cancer who are treated with sorafenib and then with sunitinib (So-Su),
      compared with sunitinib and then sorafenib (Su-So). We found that total PFS was
      not improved with So-Su compared with Su-So, but both treatment options were
      similarly effective in patients with advanced/metastatic kidney cancer. TRIAL
      REGISTRATION: ClinicalTrials.gov identifier NCT00732914, www.clinicaltrials.gov.

PMID- 25952318
TI  - Changing from primary to secondary school highlights opportunities for school
      environment interventions aiming to increase physical activity and reduce
      sedentary behaviour: a longitudinal cohort study.
AB  - BACKGROUND: There is little empirical evidence of the impact of transition from
      primary to secondary school on obesity-related risk behaviour. The purpose of
      this study was to examine the effect of a change of school system on physical
      activity (PA) and sedentary behaviour in pre-early adolescents. METHODS: Fifteen
      schools in Victoria, Australia were recruited at random from the bottom two
      strata of a five level socio-economic scale. In nine schools, students in year 6
      primary school transitioned to a different school for year 7 secondary school,
      while in six schools (combined primary-secondary), students remained in the same
      school environment from year 6 to year 7. Time 1 (T1) measures were collected
      from students (N=245) in year 6 (age 11-13). Time 2 (T2) data were collected from
      243 (99%) of the original student cohort when in year 7. PA and sedentary
      behaviour data were collected objectively (via ActiGraph accelerometer) and
      subjectively (via child self-report recall questionnaire). School environment
      data were collected via school staff survey. Change of behaviour analyses were
      conducted longitudinally i) for all students and ii) by change/no change of
      school. Mixed model regression analysis tested for behavioural interaction
      effects of changing/not changing school. RESULTS: Sixty-three percent (N=152)
      changed schools from T1 to T2. Across all students we observed declines in
      average daily moderate to vigorous physical activity (MVPA) (-4 min) and light PA
      (-23 min), and increases in average daily sedentary behaviour (16 min), weekday
      leisure screen time (17 min) and weekday homework screen time (25 min), all
      P<0.05. Compared to students who remained in the same school environment,
      students who changed school reported a greater reduction in PA intensity at
      recess and lunch, less likelihood to cycle to/from school, greater increase in
      weekday (41 mins) and weekend (45 mins) leisure screen time (P<0.05) and greater
      encouragement to participate in sport. School staff surveys identified that sport
      participation encouragement was greater in primary and combined primary-secondary
      than secondary schools (P<0.05). CONCLUSION: Transitioning from primary to
      secondary school negatively impacts on children's PA and sedentary behaviour, and
      has further compounding effects on behaviour type by changing school
      environments.

PMID- 25952320
TI  - Efficient masking of corrosion and fission products such as Ni(II) and Pd(II) in
      the presence of the minor actinide Am(III) using hydrophilic anionic or cationic
      bis-triazines.
AB  - Water soluble anionic and cationic bis-triazine ligands are able to suppress
      (mask) the extraction of corrosion and fission products such as Ni(II) and Pd(II)
      that are found in PUREX raffinates. Thus it is possible to separate these
      elements from the minor actinide Am(III). Although some masking agents have
      previously been developed that retard the extraction of Pd(II), this is the first
      time a masking agent has been developed for Ni(II).

PMID- 25952319
TI  - Integrated microRNA, mRNA, and protein expression profiling reveals microRNA
      regulatory networks in rat kidney treated with a carcinogenic dose of
      aristolochic acid.
AB  - BACKGROUND: Aristolochic Acid (AA), a natural component of Aristolochia plants
      that is found in a variety of herbal remedies and health supplements, is
      classified as a Group 1 carcinogen by the International Agency for Research on
      Cancer. Given that microRNAs (miRNAs) are involved in cancer initiation and
      progression and their role remains unknown in AA-induced carcinogenesis, we
      examined genome-wide AA-induced dysregulation of miRNAs as well as the regulation
      of miRNAs on their target gene expression in rat kidney. RESULTS: We treated rats
      with 10 mg/kg AA and vehicle control for 12 weeks and eight kidney samples (4 for
      the treatment and 4 for the control) were used for examining miRNA and mRNA
      expression by deep sequencing, and protein expression by proteomics. AA treatment
      resulted in significant differential expression of miRNAs, mRNAs and proteins as
      measured by both principal component analysis (PCA) and hierarchical clustering
      analysis (HCA). Specially, 63 miRNAs (adjusted p value < 0.05 and fold change >
      1.5), 6,794 mRNAs (adjusted p value < 0.05 and fold change > 2.0), and 800
      proteins (fold change > 2.0) were significantly altered by AA treatment. The
      expression of 6 selected miRNAs was validated by quantitative real-time PCR
      analysis. Ingenuity Pathways Analysis (IPA) showed that cancer is the top network
      and disease associated with those dysregulated miRNAs. To further investigate the
      influence of miRNAs on kidney mRNA and protein expression, we combined proteomic
      and transcriptomic data in conjunction with miRNA target selection as confirmed
      and reported in miRTarBase. In addition to translational repression and
      transcriptional destabilization, we also found that miRNAs and their target genes
      were expressed in the same direction at levels of transcription (169) or
      translation (227). Furthermore, we identified that up-regulation of 13 oncogenic
      miRNAs was associated with translational activation of 45 out of 54 cancer
      related targets. CONCLUSIONS: Our findings suggest that dysregulated miRNA
      expression plays an important role in AA-induced carcinogenesis in rat kidney,
      and that the integrated approach of multiple profiling provides a new insight
      into a post-transcriptional regulation of miRNAs on their target repression and
      activation in a genome-wide scale.

PMID- 25952321
TI  - Galectin-3 in atrial fibrillation: Simple bystander, player or both?
AB  - OBJECTIVES: Galectin-3 promotes fibrosis, and cardiac remodeling is a well
      established cause of arrhythmias. Therefore, we reviewed current evidence on the
      epidemiological and biological association between galectin-3 and atrial
      fibrillation. DESIGN AND METHODS: We performed an electronic search on Medline,
      Scopus and Web of Science, using the keywords "galectin" OR "galectin-3" AND
      "atrial fibrillation" OR "arrhythmia(s)" in the fields "title/abstract/keywords".
      RESULTS: Seven cohort studies were identified and reviewed. A significant
      association between serum galectin-3 values and the risk of atrial fibrillation
      was found in 4 studies (1 nested case-control, 2 case-control, 1 prospective),
      whereas the association could not be confirmed in a single case-control
      investigation. Serum galectin-3 value was also found to be a significant
      predictor of left atrium fibrosis, reduced left atrial volume, or decreased left
      ventricle ejection fraction in four studies (2 nested case-control, 2 case
      control). A reliable biological explanation may be brought in support of these
      findings. Activated macrophages release galectin-3, which not only contributes to
      increase macrophages accumulation in cardiac tissue and perpetuates their
      activation, but also promotes fibroblast activation and proliferation, thus
      leading to cardiac fibrosis, cardiac remodeling, myocardiocyte dysfunction and
      ultimately atrial fibrillation. The onset of atrial fibrillation further
      amplifies macrophage activation, thus completing a vicious circle that is
      mirrored by evidence of substantially increased galectin-3 values in patients
      with persistent atrial fibrillation. CONCLUSIONS: It seems reasonable to suggest
      that galectin-3 measurement holds promise for stratifying risk and outcome of
      atrial fibrillation.

PMID- 25952322
TI  - The diagnosis and management of interstitial lung diseases.

PMID- 25952323
TI  - Comparison of two different mechanical esophagogastric anastomosis in esophageal
      cancer patients: a meta-analysis.
AB  - OBJECTIVE: In this meta-analysis, we conducted a pooled analysis of clinical
      studies comparing Linear Stapled (LS) versus Circular Stapled (CS)
      esophagogastric anastomosis for esophageal cancer. METHODS: According to the
      recommendations of the Cochrane Collaboration, we established a rigorous study
      protocol. We performed a systematic electronic search of the PubMed, Embase,
      Cochrane Library, Web of Science, and Chinese Biomedical databases as well as
      Chinese scientific journals to identify articles to include in our meta-analysis.
      The primary outcomes compared were anastomotic leak, anastomotic stricture and 3
      month mortality. RESULTS: Five controlled trials comprising 840 patients (523 LS
      vs. 317 CS) were included. Primary outcomes revealed a statistically significant
      decrease in anastomotic strictures [risk ratio (RR): 0.26, 95 % confidence
      interval (CI): 0.11-0.60, P = 0.002] compared with linear stapled anastomosis.
      However, there were no significant differences between the two groups with
      respect to anastomotic leakage [risk ratio (RR): 0.80, 95 % confidence interval
      (CI): 0.40-1.58, P = 0.52] and 3-month mortality [risk ratio (RR): 0.94, 95 %
      confidence interval (CI): 0.47-1.87, P = 0.85]. CONCLUSION: There were no
      statistical differences in the rate of 3-month mortality or anastomotic leakage
      between the two groups. However, the LS method contributed to a reduced rate of
      anastomotic strictures. This meta-analysis may offer some specific suggestions
      for esophagogastric anastomosis.

PMID- 25952324
TI  - Description of a novel marine bacterium, Vibrio hyugaensis sp. nov., based on
      genomic and phenotypic characterization.
AB  - Three luminous bacteria strains have been isolated from seawater samples
      collected in the coastal regions of the Miyazaki prefecture in Japan. Analysis of
      the 16S rRNA gene sequences identified the three strains as members of the genus
      Vibrio (Vibrionaceae, Gammaproteobacteria), closely related to bacteria in the so
      called 'Harveyi clade.' The genomes of the three strains were estimated to be
      between 5.49Mbp and 5.95Mbp, with average G+C of 43.91%. The genome sequence data
      was used to estimate relatedness of the three strains to related Vibrio bacteria,
      including estimation of frequency of recombination events, calculation of average
      nucleotide identity (ANI), and a phylogenetic analysis based on concatenated
      alignment of nucleotide sequences of 135 protein coding genes. Results of these
      analyses in all cases showed the three strains forming a group clearly separate
      from previously described Vibrio species. A phenotypic analysis revealed that the
      three strains have character similar to Vibrio bacteria in the 'Harveyi clade',
      but can be differentiated from previously described species by testing for
      hydrolysis of esculin. Based on results of genomic, phylogenetic and phenotypic
      analyses presented in this study, it can be concluded that the three strains
      represent a novel species, for which the name Vibrio hyugaensis sp. nov. is
      proposed. The type strain is 090810a(T) (=LMG 28466(T)=NBRC 110633(T)).

PMID- 25952325
TI  - Drug biokinetic and toxicity assessments in rat and human primary hepatocytes and
      HepaRG cells within the EU-funded Predict-IV project.
AB  - The overall aim of Predict-IV (EU-funded collaborative project #202222) was to
      develop improved testing strategies for drug safety in the late discovery phase.
      One major focus was the prediction of hepatotoxicity as liver remains one of the
      major organ leading to failure in drug development, drug withdrawal and has a
      poor predictivity from animal experiments. In this overview we describe the use
      and applicability of the three cell models employed, i.e., primary rat
      hepatocytes, primary human hepatocytes and the human HepaRG cell line, using four
      model compounds, chlorpromazine, ibuprofen, cyclosporine A and amiodarone. This
      overview described the data generated on mode of action of liver toxicity after
      long-term repeat-dosing. Moreover we have quantified parent compound and its
      distribution in various in vitro compartments, which allowed us to develop
      biokinetic models where we could derive real exposure concentrations in vitro. In
      conclusion, the complex data set enables quantitative measurements that proved
      the concept that we can define human relevant free and toxic exposure levels in
      vitro. Further compounds have to be analyzed in a broader concentration range to
      fully exploit these promising results for improved prediction of hepatotoxicity
      and hazard assessment for humans. 

PMID- 25952326
TI  - Resveratrol induces DNA damage in colon cancer cells by poisoning topoisomerase
      II and activates the ATM kinase to trigger p53-dependent apoptosis.
AB  - Resveratrol (trans-3,4',5-trihydroxystilbene) is a natural polyphenol synthesized
      by various plants such as grape vine. Resveratrol (RSV) is a widely studied
      molecule, largely for its chemopreventive effect in different mouse cancer
      models. We propose a mechanism underlying the cytotoxic activity of RSV on colon
      cancer cells. Our data show that resveratrol induces apoptosis, as observed by
      the cleavage of PARP-1 and chromatin condensation. We show that the tumor
      suppressor p53 is activated in response to RSV and participates to the apoptotic
      process. Additionally, we show that HCT-116 p53 wt colon carcinoma cells are
      significantly more sensitive than HCT-116 p53-/- cells to RSV. RSV induces DNA
      damage including double strand breaks, as evidenced by the presence of multiple
      gamma-H2AX foci in 50% of cells after a 24 h treatment with 25 MUM RSV. The
      formation of DNA damage does not appear to rely on a pro-oxidant effect of the
      molecule, inhibition of topoisomerase I, or DNA intercalation. Rather, we show
      that DNA damage is the consequence of type II topoisomerase poisoning. Exposure
      of HCT-116 cells to RSV leads to activation of the Ataxia Telangiectasia Mutated
      (ATM) kinase, and ATM is required to activate p53.

PMID- 25952327
TI  - Improving Medication Routines and Adherence in Hypertensive African Americans:
      Finding the Needle in the Haystack.

PMID- 25952328
TI  - IncI shufflons: Assembly issues in the next-generation sequencing era.
AB  - The shufflon is a site-specific recombination system first identified in the
      IncI1 plasmid R64. The R64 shufflon consists of four segments, separated by short
      repeats, which are rearranged and inverted by the recombinase protein Rci,
      generating diversity in the C-terminal end of the PilV protein. PilV is the tip
      adhesin of the thin pilus structure involved in bacterial conjugation and may
      play a role in determining recipient cell specificity during liquid mating. The
      variable arrangements of the shufflon region would be expected to make plasmid
      assembly difficult, particularly with short-read sequencing technology, but this
      is not usually mentioned in recent publications reporting IncI plasmid sequences.
      Here we discuss the issues we encountered with assembly of IncI1 sequence data
      obtained from the Roche-454 and Illumina platforms and make some suggestions for
      assembly of the shufflon region. Comparison of shufflon segments from a
      collection of IncI1 plasmids from The Netherlands and Australia, together with
      sequences available in GenBank, suggests that the number of shufflon segments
      present is conserved among plasmids grouped together by plasmid multi-locus
      sequencing typing but the different reported arrangements of shufflon segments
      may not be meaningful. This analysis also indicated that the sequences of the
      shufflon segments are highly conserved, with very few nucleotide changes. 

PMID- 25952329
TI  - Nucleoid-associated proteins encoded on plasmids: Occurrence and mode of
      function.
AB  - Nucleoid-associated proteins (NAPs) play a role in changing the shape of
      microbial DNA, making it more compact and affecting the regulation of
      transcriptional networks in host cells. Genes that encode NAPs include H-NS
      family proteins (H-NS, Ler, MvaT, BpH3, Bv3F, HvrA, and Lsr2), FIS, HU, IHF, Lrp,
      and NdpA, and are found in both microbial chromosomes and plasmid DNA. In the
      present study, NAP genes were distributed among 442 plasmids out of 4602 plasmid
      sequences, and many H-NS family proteins, and HU, IHF, Lrp, and NdpA were found
      in plasmids of Alpha-, Beta-, and Gammaproteobacteria, while HvrA, Lsr2, HU, and
      Lrp were found in other classes including Actinobacteria and Bacilli. Larger
      plasmids frequently carried multiple NAP genes. In addition, NAP genes were more
      frequently found in conjugative plasmids than non-transmissible plasmids. Several
      host cells carried the same types of H-NS family proteins on both their plasmids
      and chromosome(s), while this was not observed for other NAPs. Recent studies
      have shown that NAP genes on plasmids and chromosomes play important roles in the
      physical and regulatory integration of plasmids into the host cell. 

PMID- 25952330
TI  - Simple non-laboratory- and laboratory-based risk assessment algorithms and
      nomogram for detecting undiagnosed diabetes mellitus.
AB  - BACKGROUND: The aim of the present study was to develop a simple nomogram that
      can be used to predict the risk of diabetes mellitus (DM) in the asymptomatic non
      diabetic subjects based on non-laboratory- and laboratory-based risk algorithms.
      METHODS: Anthropometric data, plasma fasting glucose, full lipid profile,
      exercise habits, and family history of DM were collected from Chinese non
      diabetic subjects aged 18-70 years. Logistic regression analysis was performed on
      a random sample of 2518 subjects to construct non-laboratory- and laboratory
      based risk assessment algorithms for detection of undiagnosed DM; both algorithms
      were validated on data of the remaining sample (n = 839). The Hosmer-Lemeshow
      test and area under the receiver operating characteristic (ROC) curve (AUC) were
      used to assess the calibration and discrimination of the DM risk algorithms.
      RESULTS: Of 3357 subjects recruited, 271 (8.1%) had undiagnosed DM defined by
      fasting glucose >=7.0 mmol/L or 2-h post-load plasma glucose >=11.1 mmol/L after
      an oral glucose tolerance test. The non-laboratory-based risk algorithm, with
      scores ranging from 0 to 33, included age, body mass index, family history of DM,
      regular exercise, and uncontrolled blood pressure; the laboratory-based risk
      algorithm, with scores ranging from 0 to 37, added triglyceride level to the risk
      factors. Both algorithms demonstrated acceptable calibration (Hosmer-Lemeshow
      test: P = 0.229 and P = 0.483) and discrimination (AUC 0.709 and 0.711) for
      detection of undiagnosed DM. CONCLUSION: A simple-to-use nomogram for detecting
      undiagnosed DM has been developed using validated non-laboratory-based and
      laboratory-based risk algorithms.

PMID- 25952331
TI  - A study of onychomycosis in patients attending a dermatology center in Tehran,
      Iran.
AB  - OBJECTIVE: To determine the incidence of onychomycosis based on age and sex,
      morphological pattern of the disease, predisposing factors and identification of
      fungus by direct microscopy and culture methods. METHODS: A prospective study was
      conducted on 140 patients with nail disorders. A detailed history and thorough
      examination was done in all patients. The samples were taken from patients
      clinically suspected of fingernails and toenails infections attending a
      dermatology center in Tehran, Iran. The nails were subjected to potassium
      hydroxide (KOH) examination and fungal culture on Sabouraud's dextrose agar (SDA)
      medium. RESULTS: Specimens from 79 patients (56.4%) were positive for
      onychomycosis. The mycological observations showing positive fining with KOH were
      observed in 79 (56.4%) and culture positive in 35 (25%) cases. Females were more
      infected than males. The most common age group infected was 41-60 years (40.7%).
      Toenails were affected more frequently than fingernails and dystrophic
      onychomycosis was the most common clinical type seen in 39.2% patients. From the
      culture-positive samples, yeasts were the most common pathogens isolated from 25
      (71.4%) patients, followed by non-dermatophytic moulds in 6 (17.1%) and
      dermatophytes in 4 (11.5%) patients. CONCLUSION: This study demonstrated that
      Candida species were the main agents causing onychomycosis in our region and
      accurate diagnosis of onychomycosis was based on direct microscopy and fungal
      culture.

PMID- 25952332
TI  - Millennium development goals: lessons for global mental health.

PMID- 25952333
TI  - Re-evaluation of the phenotype caused by the common MATR3 p.Ser85Cys mutation in
      a new family.

PMID- 25952334
TI  - Iron accumulation in the basal ganglia in Huntington's disease: cross-sectional
      data from the IMAGE-HD study.
AB  - OBJECTIVES: To measure iron accumulation in the basal ganglia in Huntington's
      disease (HD) using quantitative susceptibility mapping (QSM), and to ascertain
      its relevance in terms of clinical and disease severity. METHODS: In this cross
      sectional investigation, T2* weighted imaging was undertaken on 31 premanifest
      HD, 32 symptomatic HD and 30 control participants as part of the observational
      IMAGE-HD study. Group differences in iron accumulation were ascertained with QSM.
      Associations between susceptibility values and disease severity were also
      investigated. RESULTS: Compared with controls, both premanifest and symptomatic
      HD groups showed significantly greater iron content in pallidum, putamen and
      caudate. Additionally, iron accumulation in both putamen and caudate was
      significantly associated with disease severity. CONCLUSIONS: These findings
      provide the first evidence that QSM is sensitive to iron deposition in
      subcortical target areas across premanifest and symptomatic stages of HD. Such
      findings could open up new avenues for biomarker development and therapeutic
      intervention.

PMID- 25952335
TI  - Brenna's story: A critical reflection and analysis of one mother's experience of
      navigating the medical system with a child with intellectual disabilities.
AB  - Children with intellectual disabilities spend more time in the health-care system
      than mainstream children. Parents have to learn how to navigate the system by
      coordinating appointments, understanding the referral process, knowing what
      services are available, and advocating for those services. This places an
      incredible amount of responsibility on families. This article is one mother's
      personal story and reflection about her journey through the Canadian health-care
      system in Nova Scotia, with her daughter who has an intellectual disability. The
      reflection identifies moments of tension experienced by a mother and how she was
      expected to be a medical system navigator, doctor-educator, time manager, and
      care coordinator and the roles that led to feelings of repression, extreme
      frustration, and fear. A final discussion offers an analysis of her experience,
      using concepts from feminist post-structuralism. 

PMID- 25952336
TI  - Does model of maternity care make a difference to birth outcomes for young women?
      A retrospective cohort study.
AB  - BACKGROUND: Adolescent pregnancy is associated with adverse outcomes including
      preterm birth, admission to the neonatal intensive care unit, low birth weight
      infants, and artificial feeding. OBJECTIVE: To determine if caseload midwifery or
      young women's clinic are associated with improved perinatal outcomes when
      compared to standard care. DESIGN: A retrospective cohort study. SETTING: A
      tertiary Australian hospital where routine maternity care is delivered alongside
      two community-based maternity care models specifically for young women aged 21
      years or less: caseload midwifery (known midwife) and young women's clinic
      (rostered midwife). PARTICIPANTS: All pregnant women aged 21 years or less, with
      a singleton pregnancy, who attended a minimum of two antenatal visits, and who
      birthed a baby (without congenital abnormality) at the study hospital during May
      2008 to December 2012. METHODS: Caseload midwifery and young women's clinic were
      each compared to standard maternity care, but not with each other, for four
      primary outcomes: preterm birth (<37 weeks gestation), low birth weight infants
      (<2500g), neonatal intensive care unit admission, and breastfeeding initiation.
      Two analyses were performed on the primary outcomes to examine potential
      associations between maternity care type and perinatal outcomes: intention-to
      treat (model of care at booking) and treatment-received (model of care on
      admission for labour/birth). RESULTS: 1908 births were analysed by intention-to
      treat and treatment-received analyses. Young women allocated to caseload care at
      booking, compared to standard care, were less likely to have a preterm birth
      (adjusted odds ratio 0.59 (0.38-0.90, p=0.014)) or a neonatal intensive care unit
      admission adjusted odds ratio 0.42 (0.22-0.82, p=0.010). Rates of low birth
      weight infants and breastfeeding initiation were similar between caseload and
      standard care participants. Participants allocated to young women's clinic at
      booking, compared to standard care, were less likely to have a low birth weight
      infant adjusted odds ratio 0.49 (0.24-1.00, p=0.049), however when analysed by
      treatment-received, this finding was not significant. There was no difference in
      the other primary outcomes. CONCLUSIONS: Young women who were allocated to
      caseload midwifery at booking, and/or were receiving caseload midwifery at the
      time of admission for birth, were less likely to experience preterm birth and
      neonatal intensive care unit admission.

PMID- 25952337
TI  - Transforming nursing home-based day care for people with dementia into socially
      integrated community day care: process analysis of the transition of six day care
      centres.
AB  - BACKGROUND: The community-based Meeting Centres Support Programme for people with
      dementia and their carers has been proven more effective in influencing behaviour
      and mood problems of people with dementia and improving sense of competence of
      carers compared to nursing home-based day care centres for people with dementia.
      Six Dutch nursing home-based day care centres were transformed into Community
      based day care centres with carer support, according to this Meeting Centres
      model. OBJECTIVES: To determine which factors facilitate or impede the transition
      to Community-based day care. DESIGN: A process evaluation was conducted with a
      qualitative study design. SETTINGS: Six nursing home-based day care centres
      transformed into Community-based day care centres for people with dementia and
      their carers. STUDY PARTICIPANTS: Stakeholders (n=40) that were involved during
      the transition. METHODS: Factors that facilitated or impeded the transition were
      traced by means of (audiotaped and transcribed) interviews with stakeholders and
      document analysis. All data were coded by two independent researchers and
      analyzed using thematic analysis based on the Theoretical framework of adaptive
      implementation. RESULTS: Six nursing home-based day care centres successfully
      made the transition to Community-based day care with carer support. Success
      factors for the start of the project were: the innovation being in line with the
      current trend towards more outpatient care and having motivated pioneers
      responsible for the execution of the transition. Barriers were difficulties
      reaching/recruiting the target group (people with dementia and carers),
      inflexible staff and little or no experience with collaboration with community
      based care and welfare organizations. Facilitating factors during the
      implementation phase were: finding a suitable location in the community, positive
      changes in staff attitude and adoption of the new vision, and good cooperation
      with care and welfare organizations. Barriers were insufficient involvement of,
      and support from the managers of the responsible organizations, and communication
      problems with referrers of other organizations, including the GPs and case
      managers. CONCLUSIONS: The transition from nursing home-based psychogeriatric day
      care support to a community-based combined support programme for people with
      dementia and their informal carer is shown to be feasible. Successful
      implementation of this community-based combined support programme requires -
      besides motivated pioneers, a change in staff attitude and working style, a
      suitable pleasant location and collaboration with other care and welfare
      organizations - special attention for effective communication with the target
      user group and the referrers, and also how the management of the pioneer
      organizations can facilitate the staff during the transition process.

PMID- 25952339
TI  - Osteoarthritis research society international initiative on recommendations for
      conducting clinical trials in osteoarthritis: overview.

PMID- 25952338
TI  - Improving the quality of cancer staging.

PMID- 25952340
TI  - OARSI Clinical Trials Recommendations: An abbreviated regulatory guide to the
      clinical requirements for development of therapeutics in osteoarthritis.
AB  - In this brief abbreviated review of regulatory issues regarding the development
      of drugs and or devices for the treatment of osteoarthritis (OA), the steps that
      are expected by both the Food and Drug Administration (FDA) and the European
      Medicines Agency (EMA) are discussed. 

PMID- 25952341
TI  - OARSI Clinical Trials Recommendations: Key analytic considerations in design,
      analysis, and reporting of randomized controlled trials in osteoarthritis.
AB  - To highlight methodologic challenges pertinent to design, analysis, and reporting
      of results of randomized clinical trials in OA and offer practical suggestions to
      overcome these challenges. The topics covered in this paper include subject
      selection, randomization, approaches to handling missing data, subgroup analysis,
      sample size, and issues related to changing design mid-way through the study.
      Special attention is given to standardizing the reporting of results and economic
      analyses. Key findings include the importance of blinding and concealment, the
      distinction between superiority and non-inferiority trials, the need to minimize
      missing data, and appropriate analysis and interpretation of subgroup effects.
      Investigators may use the findings and recommendations advanced in this paper to
      guide design and conduct of randomized controlled trials of interventions for
      osteoarthritis. 

PMID- 25952342
TI  - OARSI Clinical Trials Recommendations: Soluble biomarker assessments in clinical
      trials in osteoarthritis.
AB  - The objective of this work was to describe requirements for inclusion of soluble
      biomarkers in osteoarthritis (OA) clinical trials and progress toward OA-related
      biomarker qualification. The Guidelines for Biomarkers Working Group,
      representing experts in the field of OA biomarker research from both academia and
      industry, convened to discuss issues related to soluble biomarkers and to make
      recommendations for their use in OA clinical trials based on current knowledge
      and anticipated benefits. This document summarizes current guidance on use of
      biomarkers in OA clinical trials and their utility at five stages, including
      preclinical development and phase I to phase IV trials. As demonstrated by this
      summary, biomarkers can provide value at all stages of therapeutics development.
      When resources permit, we recommend collection of biospecimens in all OA clinical
      trials for a wide variety of reasons but in particular, to determine whether
      biomarkers are useful in identifying those individuals most likely to receive
      clinically important benefits from an intervention; and to determine whether
      biomarkers are useful for identifying individuals at earlier stages of OA in
      order to institute treatment at a time more amenable to disease modification. 

PMID- 25952343
TI  - OARSI Clinical Trials Recommendations: Knee imaging in clinical trials in
      osteoarthritis.
AB  - Significant advances have occurred in our understanding of the pathogenesis of
      knee osteoarthritis (OA) and some recent trials have demonstrated the potential
      for modification of the disease course. The purpose of this expert opinion,
      consensus driven exercise is to provide detail on how one might use and apply
      knee imaging in knee OA trials. It includes information on acquisition
      methods/techniques (including guidance on positioning for radiography,
      sequence/protocol recommendations/hardware for magnetic resonance imaging (MRI));
      commonly encountered problems (including positioning, hardware and coil failures,
      sequences artifacts); quality assurance (QA)/control procedures; measurement
      methods; measurement performance (reliability, responsiveness, validity);
      recommendations for trials; and research recommendations. 

PMID- 25952345
TI  - OARSI Clinical Trials Recommendations: Hand imaging in clinical trials in
      osteoarthritis.
AB  - Tremendous advances have occurred in our understanding of the pathogenesis of
      hand osteoarthritis (OA) and these are beginning to be applied to trials targeted
      at modification of the disease course. The purpose of this expert opinion,
      consensus driven exercise is to provide detail on how one might use and apply
      hand imaging assessments in disease modifying clinical trials. It includes
      information on acquisition methods/techniques (including guidance on positioning
      for radiography, sequence/protocol recommendations/hardware for MRI); commonly
      encountered problems (including positioning, hardware and coil failures,
      sequences artifacts); quality assurance/control procedures; measurement methods;
      measurement performance (reliability, responsiveness, validity); recommendations
      for trials; and research recommendations. 

PMID- 25952346
TI  - OARSI Clinical Trials Recommendations: Design, conduct, and reporting of clinical
      trials for knee osteoarthritis.
AB  - The goal of this document is to update the original OARSI recommendations
      specifically for the design, conduct, and reporting of clinical trials that
      target symptom or structure modification among individuals with knee
      osteoarthritis (OA). To develop recommendations for the design, conduct, and
      reporting of clinical trials for knee OA we initially drafted recommendations
      through an iterative process. Members of the working group included
      representatives from industry and academia. After the working group members
      reviewed a final draft, they scored the appropriateness for recommendations.
      After the members voted we calculated the median score among the nine members of
      the working group who completed the score. The document includes 25
      recommendations regarding randomization, blocking and stratification, blinding,
      enhancing accuracy of patient-reported outcomes (PRO), selecting a study
      population and index knee, describing interventions, patient-reported and
      physical performance measures, structural outcome measures, biochemical
      biomarkers, and reporting recommendations. In summary, the working group
      identified 25 recommendations that represent the current best practices regarding
      clinical trials that target symptom or structure modification among individuals
      with knee OA. These updated recommendations incorporate novel technologies (e.g.,
      magnetic resonance imaging (MRI)) and strategies to address the heterogeneity of
      knee OA. 

PMID- 25952344
TI  - OARSI Clinical Trials Recommendations: Hip imaging in clinical trials in
      osteoarthritis.
AB  - Imaging of hip in osteoarthritis (OA) has seen considerable progress in the past
      decade, with the introduction of new techniques that may be more sensitive to
      structural disease changes. The purpose of this expert opinion, consensus driven
      recommendation is to provide detail on how to apply hip imaging in disease
      modifying clinical trials. It includes information on acquisition
      methods/techniques (including guidance on positioning for radiography,
      sequence/protocol recommendations/hardware for magnetic resonance imaging (MRI));
      commonly encountered problems (including positioning, hardware and coil failures,
      artifacts associated with various MRI sequences); quality assurance/control
      procedures; measurement methods; measurement performance (reliability,
      responsiveness, and validity); recommendations for trials; and research
      recommendations. 

PMID- 25952347
TI  - OARSI Clinical Trials Recommendations: Design and conduct of clinical trials for
      hip osteoarthritis.
AB  - The ability to assess the efficacy and effectiveness of an intervention for the
      treatment of hip osteoarthritis (OA) requires strong clinical trial methodology.
      This consensus paper provides recommendations based on a narrative literature
      review and best judgment of the members of the committee for clinical trials of
      hip OA. We provide recommendations on clinical trial design, outcome measures,
      including structural (radiography), and patient and physician global assessments,
      performance based measures, molecular markers and experimental endpoints
      including MRI imaging. This information can be utilized by sponsors of trials for
      new therapeutic agents for hip OA. 

PMID- 25952348
TI  - OARSI Clinical Trials Recommendations: Design and conduct of clinical trials for
      hand osteoarthritis.
AB  - Hand osteoarthritis (OA) is a very frequent disease, but yet understudied.
      However, a lot of works have been published in the past 10 years, and much has
      been done to better understand its clinical course and structural progression.
      Despite this new knowledge, few therapeutic trials have been conducted in hand
      OA. The last OARSI recommendations for the conduct of clinical trials in hand OA
      dates back to 2006. The present recommendations aimed at updating previous
      recommendations, by incorporating new data. The purpose of this expert opinion,
      consensus driven exercise is to provide evidence-based guidance on the design,
      execution and analysis of clinical trials in hand OA, where published evidence is
      available, supplemented by expert opinion, where evidence is lacking, to perform
      clinical trials in hand OA, both for symptom and for structure-modification. They
      indicate core outcome measurement sets for studies in hand OA, and list the
      methods and instruments that should be used to measure symptoms or structure. For
      both symptom- and structure-modification, at least pain, physical function,
      patient global assessment, HR-QoL, joint activity and hand strength should be
      assessed. In addition, for structure-modification trials, structural progression
      should be measured by radiographic changes. We also provide a research agenda
      listing many unsolved issues that seem to most urgently need to be addressed from
      the perspective of performing "good" clinical trials in hand OA. These updated
      OARSI recommendations should allow for better standardizing the conduct of
      clinical trials in hand OA in the next future. 

PMID- 25952349
TI  - OARSI Clinical Trials Recommendations: Design and conduct of clinical trials of
      lifestyle diet and exercise interventions for osteoarthritis.
AB  - The objective was to develop a set of "best practices" for use as a primer for
      those interested in entering the clinical trials field for lifestyle diet and/or
      exercise interventions in osteoarthritis (OA), and as a set of recommendations
      for experienced clinical trials investigators. A subcommittee of the non
      pharmacologic therapies committee of the OARSI Clinical Trials Working Group was
      selected by the Steering Committee to develop a set of recommended principles for
      non-pharmacologic diet/exercise OA randomized clinical trials. Topics were
      identified for inclusion by co-authors and reviewed by the subcommittee.
      Resources included authors' expert opinions, traditional search methods including
      MEDLINE (via PubMed), and previously published guidelines. Suggested steps and
      considerations for study methods (e.g., recruitment and enrollment of
      participants, study design, intervention and assessment methods) were
      recommended. The recommendations set forth in this paper provide a guide from
      which a research group can design a lifestyle diet/exercise randomized clinical
      trial in patients with OA. 

PMID- 25952350
TI  - OARSI Clinical Trials Recommendations: Design and conduct of clinical trials of
      surgical interventions for osteoarthritis.
AB  - To highlight methodological challenges in the design and conduct of randomized
      trials of surgical interventions and to propose strategies for addressing these
      challenges. This paper focuses on three broad areas: enrollment; intervention;
      and assessment including implications for analysis. For each challenge raised in
      the paper, we propose potential solutions. Enrollment poses challenges in
      maintaining investigator equipoise, managing conflict of interest and
      anticipating that patient preferences for specific treatments may reduce
      enrollment. Intervention design and implementation pose challenges relating to
      obsolescence, fidelity of intervention delivery, and adherence and crossover.
      Assessment and analysis raise questions regarding blinding and clustering of
      observations. This paper describes methodological problems in the design and
      conduct of surgical randomized trials and proposes strategies for addressing
      these challenges. 

PMID- 25952351
TI  - OARSI Clinical Trials Recommendations: Design and conduct of clinical trials of
      rehabilitation interventions for osteoarthritis.
AB  - A Task Force of the Osteoarthritis Research Society International (OARSI) has
      previously published a set of guidelines for the conduct of clinical trials in
      osteoarthritis (OA) of the hip and knee. Limited material available on clinical
      trials of rehabilitation in people with OA has prompted OARSI to establish a
      separate Task Force to elaborate guidelines encompassing special issues relating
      to rehabilitation of OA. The Task Force identified three main categories of
      rehabilitation clinical trials. The categories included non-operative
      rehabilitation trials, post-operative rehabilitation trials, and trials examining
      the effectiveness of devices (e.g., assistive devices, bracing, physical agents,
      electrical stimulation, etc.) that are used in rehabilitation of people with OA.
      In addition, the Task Force identified two main categories of outcomes in
      rehabilitation clinical trials, which include outcomes related to symptoms and
      function, and outcomes related to disease modification. The guidelines for
      rehabilitation clinical trials provided in this report encompass these main
      categories. The report provides guidelines for conducting and reporting on
      randomized clinical trials. The topics include considerations for entering
      patients into trials, issues related to conducting trials, considerations for
      selecting outcome measures, and recommendations for statistical analyses and
      reporting of results. The focus of the report is on rehabilitation trials for
      hip, knee and hand OA, however, we believe the content is broad enough that it
      could be applied to rehabilitation trials for other regions as well. 

PMID- 25952352
TI  - OARSI Clinical Trials Recommendations: Design and conduct of clinical trials for
      primary prevention of osteoarthritis by joint injury prevention in sport and
      recreation.
AB  - The risk of post-traumatic osteoarthritis (PTOA) substantially increases
      following joint injury. Research efforts should focus on investigating the
      efficacy of preventative strategies in high quality randomized controlled trials
      (RCT). The objective of these OARSI RCT recommendations is to inform the design,
      conduct and analytical approaches to RCTs evaluating the preventative effect of
      joint injury prevention strategies. Recommendations regarding the design,
      conduct, and reporting of RCTs evaluating injury prevention interventions were
      established based on the consensus of nine researchers internationally with
      expertise in epidemiology, injury prevention and/or osteoarthritis (OA). Input
      and resultant consensus was established through teleconference, face to face and
      email correspondence over a 1 year period. Recommendations for injury prevention
      RCTs include context specific considerations regarding the research question,
      research design, study participants, randomization, baseline characteristics,
      intervention, outcome measurement, analysis, implementation, cost evaluation,
      reporting and future considerations including the impact on development of PTOA.
      Methodological recommendations for injury prevention RCTs are critical to
      informing evidence-based practice and policy decisions in health care, public
      health and the community. Recommendations regarding the interpretation and
      conduct of injury prevention RCTs will inform the highest level of evidence in
      the field. These recommendations will facilitate between study comparisons to
      inform best practice in injury prevention that will have the greatest public
      health impact.

PMID- 25952353
TI  - OARSI Clinical Trials Recommendations: Design and conduct of implementation
      trials of interventions for osteoarthritis.
AB  - Rigorous implementation research is important for testing strategies to improve
      the delivery of effective osteoarthritis (OA) interventions. The objective of
      this manuscript is to describe principles of implementation research, including
      conceptual frameworks, study designs and methodology, with specific
      recommendations for randomized clinical trials of OA treatment and management.
      This manuscript includes a comprehensive review of prior research and
      recommendations for implementation trials. The review of literature included
      identification of seminal articles on implementation research methods, as well as
      examples of previous exemplar studies using these methods. In addition to a
      comprehensive summary of this literature, this manuscript provides key
      recommendations for OA implementation trials. This review concluded that to date
      there have been relatively few implementation trials of OA interventions, but
      this is an emerging area of research. Future OA clinical trials should routinely
      consider incorporation of implementation aims to enhance translation of findings.

PMID- 25952355
TI  - Public health: real-world network targeting of interventions.

PMID- 25952354
TI  - Social network targeting to maximise population behaviour change: a cluster
      randomised controlled trial.
AB  - BACKGROUND: Information and behaviour can spread through interpersonal ties. By
      targeting influential individuals, health interventions that harness the
      distributive properties of social networks could be made more effective and
      efficient than those that do not. Our aim was to assess which targeting methods
      produce the greatest cascades or spillover effects and hence maximise population
      level behaviour change. METHODS: In this cluster randomised trial, participants
      were recruited from villages of the Department of Lempira, Honduras. We blocked
      villages on the basis of network size, socioeconomic status, and baseline rates
      of water purification, for delivery of two public health interventions: chlorine
      for water purification and multivitamins for micronutrient deficiencies. We then
      randomised villages, separately for each intervention, to one of three targeting
      methods, introducing the interventions to 5% samples composed of either: randomly
      selected villagers (n=9 villages for each intervention); villagers with the most
      social ties (n=9); or nominated friends of random villagers (n=9; the last
      strategy exploiting the so-called friendship paradox of social networks).
      Participants and data collectors were not aware of the targeting methods. Primary
      endpoints were the proportions of available products redeemed by the entire
      population under each targeting method. This trial is registered with
      ClinicalTrials.gov, number NCT01672580. FINDINGS: Between Aug 4, and Aug 14,
      2012, 32 villages in rural Honduras (25-541 participants each; total study
      population of 5773) received public health interventions. For each intervention,
      nine villages (each with 1-20 initial target individuals) were randomised, using
      a blocked design, to each of the three targeting methods. In nomination-targeted
      villages, 951 (74.3%) of 1280 available multivitamin tickets were redeemed
      compared with 940 (66.2%) of 1420 in randomly targeted villages and 744 (61.0%)
      of 1220 in indegree-targeted villages. All pairwise differences in redemption
      rates were significant (p<0.01) after correction for multiple comparisons.
      Targeting nominated friends increased adoption of the nutritional intervention by
      12.2% compared with random targeting (95% CI 6.9-17.9). Targeting the most highly
      connected individuals, by contrast, produced no greater adoption of either
      intervention, compared with random targeting. INTERPRETATION: Introduction of a
      health intervention to the nominated friends of random individuals can enhance
      that intervention's diffusion by exploiting intrinsic properties of human social
      networks. This method has the additional advantage of scalability because it can
      be implemented without mapping the network. Deployment of certain types of health
      interventions via network targeting, without increasing the number of individuals
      targeted or the resources used, could enhance the adoption and efficiency of
      those interventions, thereby improving population health. FUNDING: National
      Institutes of Health, The Bill & Melinda Gates Foundation, Star Family
      Foundation, and the Canadian Institutes of Health Research.

PMID- 25952356
TI  - Evaluation of calcium alginate gel as electrode material for alternating current
      iontophoresis of lidocaine using excised rat skin.
AB  - Iontophoresis (IOP) is a noninvasive method of delivering medication
      transcutaneously through the skin. The electrodes used in this method should
      tightly fit to rough and irregular surfaces and be biologically safe, easy to
      handle and prepare, and cost-effective. To satisfy these requirements, calcium
      alginate gel can be a candidate electrode for IOP. Using calcium alginate gel
      electrodes, we examined whether lidocaine can be effectively transported across
      an excised rat skin by squarewave alternating current (AC) application. A
      squarewave AC with either a 70% or 80% duty cycle was continuously applied to
      0.5% calcium alginate gel electrodes containing 10% lidocaine at 10 V and 1 kHz
      for 60 min. Lidocaine concentration was measured using a spectrophotometer and
      the temperature of the gel was determined. The lidocaine concentrations for AC
      IOP at the 70% and 80% duty cycles were significantly higher than that without AC
      IOP. Furthermore, the group with the 80% duty cycle showed higher lidocaine
      concentrations than the group with the 70% duty cycle. The temperatures of all
      the groups were lower than 28  degrees C throughout the procedure. In conclusion,
      the calcium alginate gel can be used as a possible matrix for IOP electrodes.

PMID- 25952357
TI  - Factor analysis of the perception of clinical attire in the Dental Hospital,
      Tokyo Medical and Dental University.
AB  - This study analysed the perceptions of dental clinical attire among patients,
      dentists and dental students at the Dental Hospital, Tokyo Medical and Dental
      University using factor analysis to investigate what kinds of factors would
      underlie the perceptions and would guide evaluation of wearing items of dentist.
      The subjects comprised 146 patients, 97 dentists, and 81 students of the Dental
      Hospital. Using a five-point Likert scale, the subjects were asked to score their
      preferences for 35 items that might be worn by a dentist in the clinic. These
      scores were analysed using factor analysis and seven factors were extracted. The
      factors were classified into three categories; the first was a traditional factor
      representing the public self of dentists, next was casual factors representing
      the private self of individual dentists, and the other was practical factors.
      Using MANOVA and univariate ANOVA, differences in perceptions among the subjects
      were found for factors of casual items while that for traditional items not
      (P<0.05). Thus, clinical attire would be evaluated from the viewpoint of
      interplay between public self and private self of the clinician as well as
      practical aspects. The variation in perceptions would be influenced by wearers'
      gender and observers' age. 

PMID- 25952358
TI  - The Red Nucleus TNF-alpha Participates in the Initiation and Maintenance of
      Neuropathic Pain Through Different Signaling Pathways.
AB  - Previous studies have demonstrated that tumor necrosis factor-alpha (TNF-alpha)
      in the red nucleus (RN) plays a facilitated role in the development of
      neuropathic pain. Here, we further investigated the expression changes and roles
      of the downstream signaling molecules of the red nucleus TNF-alpha, including
      nuclear factor-kappa B (NF-kappaB), extracellular signal-regulated kinase (ERK),
      p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK), in
      the initiation and maintenance of neuropathic pain induced by spared nerve injury
      (SNI). Immunohistochemistry demonstrated that increased expressions of NF-kappaB,
      phospho-ERK (p-ERK) and p-p38 MAPK were observed in the RN contralateral (but not
      ipsilateral) to the nerve injury side at 3 days after SNI compared with sham
      operated and normal rats, the up-regulations of NF-kappaB and p-ERK but not p-p38
      MAPK remained at high levels till 14 days later. An elevated expression of p-JNK
      occurred at 14 days (but not 3 and 7 days) after SNI, which was later than those
      of NF-kappaB, p-ERK and p-p38 MAPK. The up-regulations of NF-kappaB, p-ERK, p-p38
      MAPK and p-JNK all could be abolished by microinjection of anti-TNF-alpha
      antibody into the RN of rats with SNI. Microinjection of NF-kappaB inhibitor
      PDTC, ERK inhibitor PD98059, p38 MAPK inhibitor SB203580 but not JNK inhibitor
      SP600125 into the RN contralateral to the nerve injury side at 3 days postinjury
      significantly alleviated SNI-induced mechanical allodynia. In addition,
      microinjection of PDTC, PD98059 and SP600125 but not SB203580 into the RN at 14
      days postinjury significantly alleviated SNI-induced mechanical allodynia. These
      results suggest that the red nucleus TNF-alpha produces the algesic effect
      through activating NF-kappaB, ERK and p38 MAPK in the early initiation stage but
      relying on the activation of NF-kappaB, ERK and JNK in the later maintenance
      stage of SNI-induced neuropathic pain. 

PMID- 25952359
TI  - Rheumatoid vasculitis: going, going, but not yet gone.

PMID- 25952362
TI  - Laparoscopic surgery in pregnant patients with acute abdomen.
AB  - AIM: Notwithstanding the significant advantages compared to open surgery,
      laparoscopic surgery was considered to be contraindicated in pregnant patients.
      Currently, there are opposing views on the safety of laparoscopic surgery during
      pregnancy, especially in last trimester. The aim of this study was to examine
      feasibility of laparoscopic surgery in pregnant women with acute abdomen.
      PATIENTS AND METHODS: We retrospectively reviewed records of all patients who
      were admitted to the Emergency Department of Cerrahpasa Medical Faculty between
      January 1995 and January 2013. All clinical data of pregnant patient who
      underwent laparoscopic surgery were analyzed including inpatient records,
      operative reports, pathology records, and delivery information. RESULTS: Fourteen
      pregnant patients (mean gestational age 19.2 weeks, ranged from 9 to 33 weeks)
      who underwent laparoscopy for appendectomy (n=11), cholecystectomy (n=2), and
      diagnostic reasons (n=1) were included. Average time of delivery was 37.4
      gestational weeks (range 35-40 weeks). Two patients had preterm labor. No
      complications such as uterine injury, fetal death, or maternal mortality were
      encountered during laparoscopic procedures CONCLUSION: Laparoscopic surgery can
      be safely performed at all trimesters of pregnancy. Laparoscopy may be useful in
      differentiation of acute abdominal pain in pregnancy and may decrease fetal loss
      due to delay in diagnosis. shorter operative time reduces negative effects of
      surgery on mother and fetus.

PMID- 25952361
TI  - Trends and protective factors of female genital mutilation in Burkina Faso: 1999
      to 2010.
AB  - BACKGROUND: The practice of Female Genital Mutilation (FGM) is common in several
      African countries and some parts of Asia. This practice is not only a violation
      of human rights, but also puts women at risk of adverse health outcomes. This
      paper analysed the trends in the prevalence of FGM in Burkina Faso and
      investigated factors that are associated with this practice following the
      enactment of an FGM law in 1996. METHODS: The study used the Burkina Faso
      Demographic and Health Survey (DHS) data sets from women aged 15 to 49 years
      undertaken in 1999, 2003 and 2010. Chi square tests were carried out to
      investigate whether there has been a change in the levels of FGM in Burkina Faso
      between 1999 and 2010 and multilevel logistic regression analysis were employed
      to identify factors that were significantly associated with undergoing FGM.
      RESULTS: The levels of FGM in Burkina Faso declined significantly from 83.6% in
      1999 to 76.1% in 2010. The percentage of women circumcised between the ages of 0
      to 5 years increased from 34.2% in 1999 to 69% in 2010. Significantly more women
      in 2010 than in 1999 were of the opinion that FGM should stop (90.6% versus
      75.1%, respectively). In 2010, the odds of getting circumcised were lowest
      amongst women that were born in the period 1990 to 1995 (immediately before the
      FGM law was enacted) compared to women born in the period 1960-1965 [OR 0.16
      (0.13,0.20)]. There was significant variation of FGM across communities. Other
      factors that were significantly associated with being circumcised were education
      level, religion, ethnicity, urban residence and age at marriage. CONCLUSIONS:
      Although the prevalence of FGM has declined in Burkina Faso, the levels are still
      high. In order to tackle the practice of FGM in Burkina Faso, the government of
      Burkina Faso and its development partners need to encourage girls' participation
      in education and target its sensitization campaigns against FGM towards Muslim
      women, women residing in rural areas and women of Mossi ethnic background.

PMID- 25952360
TI  - Non-adherence to anti-tuberculosis treatment among internal migrants with
      pulmonary tuberculosis in Shenzhen, China: a cross-sectional study.
AB  - BACKGROUND: Non-adherence to tuberculosis (TB) treatment threatens the success of
      treatment, increases the risk of TB spread, and leads to the development of drug
      resistance. The present study assessed non-adherence to anti-TB treatment among
      internal migrants with pulmonary TB living in Shenzhen, China, and examined risk
      factors for non-adherence in order to identify targets for intervention. METHODS:
      A total of 794 internal migrants with TB treated at Bao'an Hospital for Chronic
      Disease Prevention and Cure, Shenzhen, were recruited. Structured questionnaires
      were used to collect data on these patients' history and experiences with TB
      treatment. Ordinal logistic regression model were used to identify risk factors
      for non-adherence. RESULTS: The proportion of patients who had missed one dose of
      medication within two weeks was 93/794 (11.71%), and those who missed at least
      two doses of medication within two weeks was 167/794 (21.03%), with a total of
      33.74% of patients not adhering to TB treatment. Lack of knowledge about TB
      treatment and longer travel time to the nearest community health centers are
      significant predictors for non-adherence. CONCLUSIONS: The present study shows
      that non-adherence is common among internal migrants with TB. Patients who lack
      knowledge about TB treatment or have to travel far to get treated are prone to
      miss one or more doses of medication. Interventions to improve health education
      and healthcare access are essential to reduce non-adherence to TB treatment among
      internal migrants.

PMID- 25952363
TI  - Myocardial Perfusion: Characteristics of Distal Intramyocardial Arteriolar Trees.
AB  - A combination of experimental, theoretical, and imaging methodologies is used to
      examine the hierarchical structure and function of intramyocardial arteriolar
      trees in porcine hearts to provide a window onto a region of myocardial
      microvasculature which has been difficult to fully explore so far. A total of 66
      microvascular trees from 6 isolated myocardial specimens were analyzed, with a
      cumulative number of 2438 arteriolar branches greater than or equal to 40 MUm
      lumen diameter. The distribution of flow rates within each tree was derived from
      an assumed power law relationship for that tree between the diameter of vessel
      segments and flow rates that are consistent with that power law and subject to
      conservation of mass along hierarchical structure of the tree. The results
      indicate that the power law index increases at levels of arteriolar vasculature
      closer to the capillary level, consistent with a concomitant decrease in shear
      stress acting on endothelial tissue. These results resolve a long standing
      predicament which could not be resolved previously because of lack of data about
      the 3D, interconnected, arterioles. In the context of myocardial perfusion, the
      results indicate that the coefficient of variation of flow rate in pre-capillary
      distal arterioles is high, suggesting that heterogeneity of flow rate in these
      arterioles is not entirely random but may be due at least in part to active
      control.

PMID- 25952364
TI  - Plancitoxin I from the venom of crown-of-thorns starfish (Acanthaster planci)
      induces oxidative and endoplasmic reticulum stress associated cytotoxicity in
      A375.S2 cells.
AB  - The crown-of-thorns starfish Acanthaster planci is a venomous starfish whose
      venom provokes strong cytotoxicity. In the present study, the purified cytotoxic
      toxin of A. planci venom (CAV) was identified as plancitoxin I protein by mass
      spectrum analyses. This study aims to investigate the molecular mechanism
      underlying the cytotoxicity function of plancitoxin I by focusing on the
      oxidative stress, mitochondrial dysfunction and endoplasmic reticulum (ER) stress
      pathway in human melanoma A375.S2 cells. The results indicated that after being
      treated with CAV toxin, A375.S2 cells significantly decreased viability in a dose
      dependent manner. The CAV was found to reduce the cellular antioxidant enzymes
      such as SOD and CAT, and there was a significant decrease in total thiol level
      and mtDNA integrity, and it enhanced the lipid peroxidation. In addition, CAV
      increased cytosolic Ca(2+) concentration, and enhanced the expression of the ER
      molecular chaperones GRP78 and CHOP in a dose-dependent manner. CAV significantly
      elevated the activity of caspase-3, -8 and -9, and reduced the ratio of Bcl
      2/Bax. The cells exhibited apoptosis were determined by using propidium iodide
      (PI) staining of DNA fragmentation (sub-G1 peak). In summary, the results
      demonstrated that plancitoxin I inhibits the proliferation of A375.S2 cells
      through induction of oxidative stress, mitochondrial dysfunction and ER stress
      associated apoptosis.

PMID- 25952365
TI  - Contralateral reexpansion pulmonary edema with ipsilateral collapsed lung after
      pleural effusion drainage: a case report.
AB  - Reexpansion pulmonary edema is a rare but potentially life-threatening condition
      that occurs when a collapsed lung reexpands, usually in the same side of
      collapsed lung. We present a rare case in which a 57-year-old Korean man had a
      large amount of malignant pleural effusion. After undergoing tube thoracostomy
      drainage for the pleural effusion, a contralateral reexpansion pulmonary edema
      developed while the ipsilateral lung was half collapsed. The patient was dyspneic
      with an oxygen saturation that dropped to 66 %. After conservative treatment with
      oxygen therapy, steroid administration, and negative suction application (suction
      pressure of -20 cm H2O) in the right pleural cavity for five days, the right lung
      could be fully expanded without development of reexpansion pulmonary edema, and
      the reexpansion pulmonary edema in the left lung resolved. Although it is a very
      rare condition, it is important to know that contralateral occurrence of
      reexpansion pulmonary edema can occur, especially when the ipsilateral lung is
      collapsed. Being aware of this potential condition can allow for early and proper
      management.

PMID- 25952366
TI  - Self-assembly of cricoid proteins induced by "soft nanoparticles": an approach to
      design multienzyme-cooperative antioxidative systems.
AB  - A strategy to construct high-ordered protein nanowires by electrostatic assembly
      of cricoid proteins and "soft nanoparticles" was developed. Poly(amido amine)
      (PAMAM) dendrimers on high generation that have been shown to be near-globular
      macromolecules with all of the amino groups distributing throughout the surface
      were ideal electropositive "soft nanoparticles" to induce electrostatic assembly
      of electronegative cricoid proteins. Atomic force microscopy and transmission
      electron microscopy all showed that one "soft nanoparticle" (generation 5 PAMAM,
      PD5) could electrostatically interact with two cricoid proteins (stable protein
      one, SP1) in an opposite orientation to form sandwich structure, further leading
      to self-assembled protein nanowires. The designed nanostructures could act as
      versatile scaffolds to develop multienzyme-cooperative antioxidative systems. By
      means of inducing catalytic selenocysteine and manganese porphyrin to SP1 and
      PD5, respectively, we successfully designed antioxidative protein nanowires with
      both excellent glutathione peroxidase and superoxide dismutase activities. Also,
      the introduction of selenocysteine and manganese porphyrin did not affect the
      assembly morphologies. Moreover, this multienzyme-cooperative antioxidative
      system exhibited excellent biological effect and low cell cytotoxicity. 

PMID- 25952367
TI  - Cognitive and affective benefits of combination therapy with galantamine plus
      cognitive rehabilitation for Alzheimer's disease.
AB  - AIM: The aim of the present study was to compare the effects of a galantamine
      only therapy and a combination therapy with galantamine plus ambulatory cognitive
      rehabilitation for Alzheimer's disease patients. METHODS: For this retrospective
      cohort study, we enrolled 86 patients with Alzheimer's disease, dividing them
      into two groups - a galantamine only group (group G, n = 45) and a combination
      with galantamine plus ambulatory rehabilitation group (group G + R, n = 41). The
      present cognitive rehabilitation included a set of physical therapy, occupational
      therapy and speech therapy for 1-2 h once or twice a week. We compared the Mini
      Mental State Examination and Frontal Assessment Battery for cognitive assessment,
      and Geriatric Depression Scale, Apathy Scale, and Abe's Behavioral and
      Psychological Symptoms of Dementia score for affective assessment in two groups
      over 6 months. RESULTS: The baseline Mini-Mental State Examination score was 20.2
      and 18.7 in groups G and G + R, respectively. Other baseline data (Frontal
      Assessment Battery, Geriatric Depression Scale, Apathy Scale, and Abe's
      Behavioral and Psychological Symptoms of Dementia) were not different between the
      two groups. Although group G kept all the scores stable until 6 months of the
      treatment, the Apathy Scale score showed a significant improvement in group G + R
      as early as 3 months, followed by the Mini-Mental State Examination and Frontal
      Assessment Battery improvements at 6 months (*P = 0.04 and *P = 0.02,
      respectively). The Geriatric Depression Scale and Abe's Behavioral and
      Psychological Symptoms of Dementia did not show any changes. CONCLUSION: The
      combination therapy of galantamine plus ambulatory cognitive rehabilitation
      showed a superior benefit both on cognitive and affective functions than
      galantamine only therapy in Alzheimer's disease patients.

PMID- 25952368
TI  - The changes in miR-130b levels in human serum and the correlation with the
      severity of diabetic nephropathy.
AB  - BACKGROUND: Circulating microRNA 130b has been closely associated with multiple
      diseases in humans such as cancer, obesity and diabetes mellitus. This study
      evaluates the correlation between serum miR-130b and the severity of diabetic
      nephropathy evaluated by measurement of albuminuria. METHODS: Three hundred
      twenty-seven patients with type 2 diabetes mellitus (T2DM) were divided into
      three groups: normoalbuminuria group [diabetes mellitus, urinary albumin to
      creatinine ratio (UACR) < 30 mg/g, n = 137], microalbuminuria group (DN1, UACR 30
      300 mg/g, n = 122) and macroalbuminuria group (DN2, UACR > 300 mg/g, n = 68). The
      levels of serum miR-130b were validated by real-time polymerase chain reaction.
      Serum transforming growth factor beta1 (TGF-beta1), hypoxia inducible factor
      1alpha (HIF-1alpha) and fibronectin were determined by enzyme-linked
      immunosorbent assay. RESULTS: Compared with control, serum miR-130b levels were
      significantly decreased in T2DM patients and further decreased in the patients of
      diabetes mellitus, DN1 and DN2 groups (p < 0.001). Furthermore, age-adjusted and
      sex-adjusted regression analyses showed that decreased level of serum miR-130b,
      increased levels of glycated haemoglobin (HbA1c ), homeostatic model assessment
      of insulin resistance (HOMA-IR), triglyceride (TG), low-density lipoprotein
      (LDL), serum creatinine, blood urea nitrogen (BUN), TGF-beta1, HIF-1alpha and
      fibronectin were significantly correlated with UACR (p < 0.05). In addition,
      serum miR-130b levels were inversely correlated with HbA1c , HOMA-IR, TG, LDL,
      BUN, TGF-beta1, HIF-1alpha and FN (p < 0.05). CONCLUSION: Our findings suggest
      that serum miR-130b may be a new biomarker for the early diagnosis of DN in T2DM.
      Circulating miR-130b may possibly be involved in the pathological mechanism of
      DN, such as lipid metabolic disorders, oxidative stress, extracellular matrix
      deposition and renal fibrosis.

PMID- 25952369
TI  - Increased cardiovascular risk in subjects with a low prevalence of classic
      cardiovascular risk factors: The inflammatory bowel disease paradox.

PMID- 25952371
TI  - Dealing with natural disasters.

PMID- 25952372
TI  - More older people receive emergency cancer diagnoses.

PMID- 25952373
TI  - Age UK's integrated pilot to be introduced across England.

PMID- 25952370
TI  - Digital gene expression approach over multiple RNA-Seq data sets to detect
      neoblast transcriptional changes in Schmidtea mediterranea.
AB  - BACKGROUND: The freshwater planarian Schmidtea mediterranea is recognised as a
      valuable model for research into adult stem cells and regeneration. With the
      advent of the high-throughput sequencing technologies, it has become feasible to
      undertake detailed transcriptional analysis of its unique stem cell population,
      the neoblasts. Nonetheless, a reliable reference for this type of studies is
      still lacking. RESULTS: Taking advantage of digital gene expression (DGE)
      sequencing technology we compare all the available transcriptomes for S.
      mediterranea and improve their annotation. These results are accessible via web
      for the community of researchers. Using the quantitative nature of DGE, we
      describe the transcriptional profile of neoblasts and present 42 new neoblast
      genes, including several cancer-related genes and transcription factors.
      Furthermore, we describe in detail the Smed-meis-like gene and the three Nuclear
      Factor Y subunits Smed-nf-YA, Smed-nf-YB-2 and Smed-nf-YC. CONCLUSIONS: DGE is a
      valuable tool for gene discovery, quantification and annotation. The application
      of DGE in S. mediterranea confirms the planarian stem cells or neoblasts as a
      complex population of pluripotent and multipotent cells regulated by a mixture of
      transcription factors and cancer-related genes.

PMID- 25952374
TI  - Attendance by young people puts services under pressure.

PMID- 25952375
TI  - Awarded nurse of the year for tackling domestic violence.

PMID- 25952376
TI  - Attacks on children reduced by one fifth in England and Wales.

PMID- 25952377
TI  - Scrap pay for unsocial hours and nurses will retaliate, warns RCN.

PMID- 25952378
TI  - Call for donations after earthquake devastates Nepal.

PMID- 25952379
TI  - More patients seen in Scotland thanks to hard work of staff.

PMID- 25952380
TI  - Making sure children receive good care closer to home.

PMID- 25952381
TI  - Poisoning from carbon monoxide is not simply a winter problem.

PMID- 25952382
TI  - Are preceptorships effective?

PMID- 25952383
TI  - Board's eye view--Staff development.

PMID- 25952391
TI  - Verbal or written advice?

PMID- 25952392
TI  - Role of research in urgent care.

PMID- 25952398
TI  - Management of febrile convulsion in children.
AB  - The causes of febrile convulsions are usually benign. Such convulsions are common
      in children and their long-term consequences are rare. However, other causes of
      seizures, such as intracranial infections, must be excluded before diagnosis,
      especially in infants and younger children. Diagnosis is based mainly on history
      taking, and further investigations into the condition are not generally needed in
      fully immunised children presenting with simple febrile convulsions. Treatment
      involves symptom control and treating the cause of the fever. Nevertheless,
      febrile convulsions in children can be distressing for parents, who should be
      supported and kept informed by experienced emergency department (ED) nurses. This
      article discusses the aetiology, clinical presentation, diagnosis and management
      of children with febrile convulsion, and best practice for care in EDs. It also
      includes a reflective case study to highlight the challenges faced by healthcare
      professionals who manage children who present with febrile convulsion. 

PMID- 25952399
TI  - Mild induced hypothermia after return of spontaneous circulation.
AB  - There is evidence to suggest that the use of mild induced hypothermia (MIH) in
      patients who have had cardiac arrest can improve neurological prognosis and long
      term survival to discharge rates, although there is some debate in the literature
      on the efficacy of the procedure. This article reviews the literature on MIH with
      the aim of increasing emergency nurses' awareness, knowledge and understanding of
      the evidence for the procedure. 

PMID- 25952401
TI  - Finding solutions.

PMID- 25952400
TI  - Ultrasonography and radiography: a comparison.
AB  - Distal limb fractures are common presentations to emergency departments and minor
      injury units (MIUs). The authors conducted a study of the usefulness and
      efficiency of portable ultrasound in detecting the presence of minor fractures in
      patients presenting to Cirencester Hospital's MIU. Patients above two years of
      age about whom there was a high clinical suspicion of a closed fracture of the
      distal forearm or wrist, or the lower limb, were included in the study. After
      initial clinical assessments, the patients were referred for X-ray, as is usual
      for such patients, and also for ultrasound imaging of their injured sites. The
      ultrasound and radiograph images were subsequently compared for injury and
      presence of fracture, and this article discusses the results. 

PMID- 25952402
TI  - Excellence in healthcare is celebrated in The BMJ Awards 2015.

PMID- 25952403
TI  - Dental erosion among children aged 3-6 years and its associated indicators.
AB  - OBJECTIVES: To analyze the status quo of dental erosion in 3- to 6-year-old
      children in Shanghai. METHODS: A stratified, cluster, multistage random sampling
      methods was applied to 3- to 6-year-old children in Shanghai in 2012. Both
      questionnaire and clinical oral examination were performed in the survey. The
      questionnaire included general information, such as age, gender, parental
      education, dietary habit, oral health behavior, general medical health, and
      socioeconomic status. The clinical examination focused on the eroded tooth
      surface and dental erosion extent. SPSS v19.0 software package was utilized for
      statistical analysis. RESULTS: A total of 1,837 children aged 3-6 years were
      randomly selected in Shanghai. The overall dental erosion prevalence was 15.1
      percent. Among different age groups, a relatively high prevalence of 17.1 percent
      was found in the 4-year-old group, and a relatively low prevalence of 12.0
      percent was observed in the 3-year-old group. Surprisingly, there was no
      significant difference among the four age groups. The occurrence of dental
      erosion was influenced by habits of vinegar/coffee/tea consumption, mother's
      educational background, birthplace, and regurgitation (P < 0.05). CONCLUSION: The
      dental erosion prevalence in 3- to 6-year-old children in Shanghai appears to be
      close to that of other Chinese provinces as well as that observed in most of
      surveys carried out in different parts of the world. Efforts should be made to
      raise public awareness about the disease. Moreover, further studies targeted to
      explore the relationship between dental erosion and risk factors are needed. It
      is also necessary to establish a unified diagnostic standard for future
      epidemiological investigations.

PMID- 25952404
TI  - Correlating Parkinson's disease motor symptoms with three-dimensional [(18)F]FP
      CIT PET.
AB  - PURPOSE: To investigate the correlation between the striatal three-dimensional
      location and the Unified Parkinson's Disease Rating Scale (UPDRS) motor score in
      the context of idiopathic Parkinson's disease (PD) through radiolabeled N-(3
      fluoropropyl)-2beta-carboxymethoxy-3beta-(4-iodophenyl) nortropane positron
      emission tomography/computed tomography (FP-CIT PET/CT). MATERIALS AND METHODS:
      In this cross-sectional study, we assessed the UPDRS motor score and performed FP
      CIT PET/CT in patients with PD. Thirty-eight patients with idiopathic PD [average
      70 years of age (range 49-86); male:female ratio 12:26] were enrolled. The
      correlation between FP-CIT PET/CT and the UPDRS III scores was investigated after
      the transformation of PET images by an alternative method using MATLAB. RESULTS:
      Left caudate nucleus uptake negatively correlated with UPDRS items 18, 20 (face),
      22 (right arm and leg), 23, 24 (right side), 26 (right side), 27, 30, and 31,
      while right caudate nucleus uptake positively correlated with items 18, 22 (left
      arm), 26, and 29. Putamen uptake correlated with items 22 and 25. Left caudate
      nucleus uptake positively correlated with axial and akinetic-rigidity symptoms.
      CONCLUSIONS: FP-CIT uptake in specific basal ganglia structures strongly
      correlated with the UPDRS III motor score. Among these, the left caudate nucleus
      exhibited the strongest relationship with axial and akinetic-rigidity PD
      symptoms.

PMID- 25952405
TI  - Can CT angiography reconstructed from CT perfusion source data on a 320-section
      volume CT scanner replace conventional CT angiography for the evaluation of
      intracranial arteries?
AB  - PURPOSE: To compare conventional CT angiography (CTA) and CTA reconstructed from
      CT perfusion source data (perfusion CTA) acquired on a 320-section CT scanner for
      the evaluation of intracranial arteries. MATERIALS AND METHODS: Our study
      included 7 patients who had undergone trapping of an intracranial aneurysm and
      placement of a bypass. All underwent conventional and perfusion CTA and digital
      subtraction angiography (DSA). Using DSA as the gold standard, 2 radiologists
      evaluated 10 arterial segments on conventional and perfusion CTA images. On a 4
      point scale they independently scored the image quality and vascular
      visualization of the intracranial arteries on the conventional and perfusion CTA
      images. The effective radiation dose to each patient was also recorded. RESULTS:
      A total of 65 arterial segments without apparent abnormalities were assessed.
      While the mean image quality score tended to be slightly higher for conventional
      than perfusion CTA, there was no significant difference. The effective dose for
      perfusion and conventional CTA with unenhanced CT was 4.2 mSv and 3.1 mSv,
      respectively, for all patients. CONCLUSION: For the evaluation of intracranial
      arteries using DSA as the gold standard, perfusion CTA yields image quality and
      vascular visualization similar to conventional CTA at an acceptable radiation
      dose.

PMID- 25952407
TI  - Investigation of structural resorption behavior of biphasic bioceramics with help
      of gravimetry, MUCT, SEM, and XRD.
AB  - Resorbable bone substitute materials are widely used for bone augmentation after
      tumor resection, parallel to implant placement, or in critical size bone defects.
      In this study, the structural dissolution of a biphasic calcium phosphate bone
      substitute material with a hydroxyapatite (HA)/tricalcium phosphate (beta-TCP)
      ratio of 60/40 was investigated by repeatedly placing porous blocks in EDTA
      solution at 37  degrees C. At several time points, the blocks were investigated
      by SEM, uCT, and gravimetry. It was found that always complete 2-3 um sized
      grains were removed from the structure and that the beta-TCP is dissolved more
      rapidly. This selective dissolution of the beta-TCP grains was confirmed by XRD
      measurements. The blocks were eroded from the outside toward the center. The
      structure remained mechanically stable because the central part showed a delayed
      degradation and because the slower dissolving HA grains preserved the integrity
      of the structure.

PMID- 25952408
TI  - Predictive Value of the Neutrophil/Lymphocyte Ratio in Peritoneal and/or
      Metastatic Disease at Staging Laparoscopy for Gastric and Esophageal
      Adenocarcinoma.
AB  - BACKGROUND: Despite advances in imaging techniques, peritoneal and/or metastatic
      disease have been identified by staging laparoscopy in up to 50 % of patients
      with a negative preoperative imaging. Neutrophil to lymphocyte ratio (NLR) has
      been recently shown as a prognostic factor in gastric and esophageal cancers.
      METHODS: We retrospectively reviewed the medical records of 117 patients with
      early gastric and lower esophagus adenocarcinoma that were referred for staging
      laparoscopy in the last two years in the University College Hospital, London.
      Complete blood count was performed preceding staging laparoscopy. The NLR was
      calculated by dividing the absolute neutrophil count by the absolute lymphocyte
      count; a high NLR was defined >=3.28. We evaluated the predictive power of a high
      NLR for a positive staging laparoscopy. RESULTS: The median age was 66.7 years;
      87 (74.4 %) were male. Forty-four percent of the tumors were located at the
      gastroesophageal junction, 18 % were esophageal, and 38 % were gastric. Twenty
      five (21.4 %) patients were found to have peritoneal or metastatic disease on
      staging laparoscopy. NLR >=3.28 was an independent predicting factor for the
      discovery of peritoneal and/or metastatic disease (OR 3.9, 95 % CI: 1.54-9.86, p
      = 0.005). The median value of NLR was significantly higher in patients for whom
      the laparoscopy had discovered peritoneal or metastatic disease, than in those it
      had not (3.3 vs. 2.2, p = 0.011). CONCLUSION: Our findings suggest that the NLR
      may be reliable for predicting the presence of peritoneal or metastatic
      involvement on staging laparoscopy, in patients with early gastric cancer or
      lower esophageal cancer.

PMID- 25952409
TI  - Breath methane in functional constipation: response to treatment with Ispaghula
      husk.
AB  - BACKGROUND: Colonic fermentation produces hydrogen (H2 ), and also produces
      methane (CH4 ) in subjects with methanogenic flora (M+). Methane production has
      been associated with chronic constipation (CC) and with changes in gut motility.
      To determine CH4 production in CC compared to controls, and to assess whether the
      therapeutic response to Ispaghula husk in CC differs between CH4 -producers and
      non-producers. METHODS: Forty-eight patients with functional constipation or
      irritable bowel syndrome-constipation and 19 healthy age-and-sex-matched
      volunteers (HV) filled in a 1-week symptom diary and a dietary questionnaire.
      They then underwent a lactulose breath test (LBT) to measure H2 and CH4
      production (peak and area under the time-concentration curve, AUC-) and a colonic
      transit time (CTT) assessment. In patients, measurements were repeated after a 4
      week treatment with Ispaghula husk. KEY RESULTS: Prevalence of M+ in patients was
      60.5% vs 52.6% in HV (p = 0.37). Patients had significantly longer CTT and
      greater production of both H2 and CH4 during LBT. There was a significant
      correlation between CH4 production and CTT (r = 0.51; p = 0.07). Treatment
      response rate was similar for M+ and M- patients (58.3% vs 52.9%; p = 0.76) as
      were the increases in bowel movements and Bristol score, changes in abdominal
      discomfort and bloating. In M+, treatment reduced CTT (-10 +/- 35 h; p = 0.029 vs
      baseline) and CH4 levels: peak CH4 (-13 +/- 24 ppm; p = 0.014) and CH4 -AUC (-817
      +/- 3100 ppm/min; p = 0.04). CONCLUSIONS & INFERENCES: Although CH4 production
      has been associated with CC pathophysiology, we found that CH4 status did not
      negatively affect the response to Ispaghula husk treatment. The measurement of
      CH4 levels as a biomarker tool for CC requires further appraisal.

PMID- 25952410
TI  - Teaching undergraduate biomechanics with Just-in-Time Teaching.
AB  - Biomechanics education is a vital component of kinesiology, sports medicine, and
      physical education, as well as for many biomedical engineering and bioengineering
      undergraduate programmes. Little research exists regarding effective teaching
      strategies for biomechanics. However, prior work suggests that student learning
      in undergraduate physics courses has been aided by using the Just-in-Time
      Teaching (JiTT). As physics understanding plays a role in biomechanics
      understanding, the purpose of study was to evaluate the use of a JiTT framework
      in an undergraduate biomechanics course. This two-year action-based research
      study evaluated three JiTT frameworks: (1) no JiTT; (2) mathematics-based JiTT;
      and (3) concept-based JiTT. A pre- and post-course assessment of student learning
      used the biomechanics concept inventory and a biomechanics concept map. A general
      linear model assessed differences between the course assessments by JiTT
      framework in order to evaluate learning and teaching effectiveness. The results
      indicated significantly higher learning gains and better conceptual understanding
      in a concept-based JiTT course, relative to a mathematics-based JiTT or no JiTT
      course structure. These results suggest that a course structure involving concept
      based questions using a JiTT strategy may be an effective method for engaging
      undergraduate students and promoting learning in biomechanics courses. 

PMID- 25952411
TI  - Presidential address.

PMID- 25952406
TI  - Clk post-transcriptional control denoises circadian transcription both temporally
      and spatially.
AB  - The transcription factor CLOCK (CLK) is essential for the development and
      maintenance of circadian rhythms in Drosophila. However, little is known about
      how CLK levels are controlled. Here we show that Clk mRNA is strongly regulated
      post-transcriptionally through its 3' UTR. Flies expressing Clk transgenes
      without normal 3' UTR exhibit variable CLK-driven transcription and circadian
      behaviour as well as ectopic expression of CLK-target genes in the brain. In
      these flies, the number of the key circadian neurons differs stochastically
      between individuals and within the two hemispheres of the same brain. Moreover,
      flies carrying Clk transgenes with deletions in the binding sites for the miRNA
      bantam have stochastic number of pacemaker neurons, suggesting that this miRNA
      mediates the deterministic expression of CLK. Overall our results demonstrate a
      key role of Clk post-transcriptional control in stabilizing circadian
      transcription, which is essential for proper development and maintenance of
      circadian rhythms in Drosophila. 

PMID- 25952412
TI  - Valedictory address.

PMID- 25952413
TI  - Orthodontics: 24-month braces.

PMID- 25952414
TI  - Better served in a dental practice.

PMID- 25952415
TI  - Oral surgery: Suturing in the real world.

PMID- 25952416
TI  - Unrelenting diatribe.

PMID- 25952417
TI  - Case reports: Oral vitiligo.

PMID- 25952418
TI  - Case reports: Misdiagnosed herpes zoster.

PMID- 25952419
TI  - A day in the life: Love on ice for Mark and Rebecca.

PMID- 25952421
TI  - Xylitol benefits still unproven.

PMID- 25952425
TI  - Dentists overestimate patient worries about who's delivering their dental care.

PMID- 25952428
TI  - Does apical periodontitis have systemic consequences? The need for well-planned
      and carefully conducted clinical studies.
AB  - Apical periodontitis, infection of the root canal system, may have systemic
      consequences. This proposal has been brought forward many times in dentistry
      literature but the general consensus is that there is no scientific basis for an
      association between endodontic infections and general health. This opinion paper
      argues that, in order to obtain such a scientific basis, or to rule out the issue
      all together, we need carefully designed longitudinal challenge model (that is,
      intervention) studies in which we follow specific biomarkers of inflammation.
      These biomarkers can be those that are currently being substantiated in chronic
      inflammation and low-grade inflammation studies in medicine and nutritional
      science, where the presence of these inflammatory disorders is linked to systemic
      outcomes. A list of suggested biomarkers has been included. 

PMID- 25952429
TI  - Case series of extra pulmonary tuberculosis presenting as facial swelling.
AB  - In England there were 7,290 cases of tuberculosis (TB) reported in 2013. The area
      with the highest incidence of the disease in England is London, with hotspots in
      other urban areas. TB affecting the head and neck is rare. We present three such
      cases of TB presenting as pre-auricular swelling. Two of the patients were
      initially misdiagnosed as having dental infection, demonstrating the importance
      of taking a good history and considering the differential diagnosis of TB when
      appropriate. TB remains a potentially fatal disease that should be considered in
      patients presenting with facial swelling where common causes have been excluded. 

PMID- 25952434
TI  - Comparative accuracy of different members of the dental team in detecting
      malignant and non-malignant oral lesions.
AB  - OBJECTIVES: Role substitution between primary care dentists (PCDs) and dental
      hygienists and therapists is increasingly being used in a number of different
      countries. Opponents to this development argue that it is unsafe and frequently
      cite the potential for missing oral malignancy as an inherent danger. The aim of
      the present study was to determine the comparative diagnostic test accuracy of
      different members of the dental team when differentiating between standardised
      photographs of mouth cancer, potentially malignant disorders and benign oral
      lesions. METHODS: A total of 192 dental professionals, comprising 96 PCDs, 63 DH
      Ts, nine hospital-based dental staff and 24 other dental professionals were
      sampled purposively. Following orientation, participants were asked to score 90
      clinical photographs that depicted cases of oral squamous cell carcinoma,
      potentially malignant disorders and non-malignant lesions of the oral mucosa. For
      each photograph participants were asked to determine whether they felt the lesion
      was representative of carcinoma, a potentially malignant disorder (test
      positive), or whether the lesion was benign (test negative). They were also asked
      to record their confidence in their decision on a 0-10 scale. Judgement decisions
      were compared against the known histopathological diagnosis of each lesion.
      Sensitivity and specificity were calculated for each participant and clinical
      group. RESULTS: The diagnostic test accuracy of PCDs and DH-Ts was similar. There
      was a median sensitivity of 81% Interquartile range (IQR) 19%) for PCDs and 77%
      (IQR 19%) for DH-T, with specificity of 73% (IQR 16%) and 69% (IQR 17%)
      respectively. DH-Ts missed fewer frank malignant lesions compared to PCDs.
      CONCLUSION: The performance of PCDs and DH-Ts when differentiating between mouth
      cancer, potentially malignant disorders and benign lesions is comparable. DH-Ts
      should be regarded as being as competent as PCDs as front-line healthcare workers
      with regard to detection of mouth cancer. However, considerable heterogeneity in
      detection was found within both clinical groups, suggesting that training remains
      paramount.

PMID- 25952435
TI  - Oral health effects, brushing habits and management of methamphetamine users for
      the general dental practitioner.
AB  - BACKGROUND: Methamphetamine is a synthetic drug commonly abused in South Africa
      and is highly addictive. Users have a higher prevalence of dental caries compared
      to non-users and the classical caries pattern found in methamphetamine users is
      termed 'meth mouth'. The increased consumption of soft drinks and the absence of
      saliva are the main risk factors for 'meth mouth'. AIM: To determine the oral
      health status of individuals using methamphetamine. METHOD: A cross-sectional
      study was conducted on a convenience sample of 308 self-reported methamphetamine
      users at 22 specialised substance addiction treatment centres in the Western
      Cape, South Africa. RESULTS: There was a significant difference in tooth brushing
      frequency when using methamphetamine (p = 0.0000022; chi(2) = 23.84; OR = 3.25).
      The mean decayed, missing and filled teeth score was ten and there was an
      association between the mean number of decayed teeth and the duration of drug
      addiction (p = 0.0071; chi(2) = 12.07). Users who were using methamphetamine for
      less than four years had fewer missing teeth compared to those who were using
      methamphetamine for more than four years. CONCLUSIONS: When methamphetamine abuse
      is detected, the dentist can play a key role in early management of drug
      addiction by referring the patient to specialised substance addiction treatment
      centres. In addition, by restoring the dental appearance, users may regain their
      self-esteem and improve their oral health quality of life.

PMID- 25952436
TI  - Why don't dentists talk to patients about oral cancer?
AB  - OBJECTIVES: Up to half of oral cancer patients are diagnosed with advanced
      lesions. One route to early diagnosis could involve dentists raising awareness of
      oral cancer through discussions with patients, emphasising prompt help-seeking.
      This study explores opinions and practices of dentists regarding discussing oral
      cancer with patients including views on barriers and facilitators. DESIGN:
      Qualitative in-depth interviews.Setting Dentists working in general dental
      practices in the United Kingdom were interviewed in 2013. SUBJECTS AND METHODS:
      In-depth interviews with dentists (n = 16) were conducted. Interviews were audio
      recorded and transcribed. Data was analysed using framework analysis. RESULTS:
      Dentists recognised the importance of raising awareness but identified several
      barriers to discussions including system factors (for example, time constraints
      and a lack of financial incentive), patient factors (for example, fear of
      invoking undue anxiety) and dentist factors (for example, a lack of sufficient
      knowledge, training and self-confidence). Facilitators included developing
      practice standards and good dentist-patient relationships. CONCLUSION: Identified
      barriers may hold back efforts to raise awareness of oral cancer and could be
      targeted in future initiatives to encourage early detection.

PMID- 25952437
TI  - Balancing the risks and benefits associated with cosmetic dentistry - a joint
      statement by UK specialist dental societies.
AB  - Cosmetic dentistry has become increasingly popular, largely as a result of social
      trends and increased media coverage. This understandable desire for the alleged
      'perfect smile' needs to be tempered with an appropriate awareness of the
      significant risks associated with invasive cosmetic procedures such as veneers
      and crowns. Patients need to be properly informed that elective removal of
      healthy enamel and dentine can result in pulpal injury and poorer periodontal
      health in the longer term, particularly if they are young. The duty of candour
      means that they ought to be informed that aggressive reduction of sound tooth
      tissue is not biologically neutral and results in structural weakening of their
      teeth. Less invasive procedures such as bleaching on its own or for example,
      combined with direct resin composite bonding, can satisfy many patient's demands,
      while still being kinder to teeth and having much better fall-back positions for
      their future requirements. It is the opinion of the British Endodontic Society,
      British Society for Restorative Dentistry, Restorative Dentistry UK, Dental
      Trauma UK, British Society of Prosthodontics and the British Society of
      Paediatric Dentistry that elective invasive cosmetic dental treatments can result
      in great benefit to patients, but that some aggressive treatments used to achieve
      them can produce significant morbidities in teeth which were previously healthy.
      This is a worrying and growing problem with many ethical, legal and biologic
      aspects, but many adverse outcomes for patients who request cosmetic dental
      improvements are preventable by using biologically safer initial approaches to
      treatment planning and its provision. 

PMID- 25952455
TI  - The laryngeal tube - a helpful tool for cardiopulmonary resuscitation in the
      dental office?
AB  - BACKGROUND: Supraglottic airway adjuncts such as the laryngeal tube (LT) have
      been recommended to be used by cardiopulmonary resuscitation (CPR) first
      responders.Objective This study aims to evaluate the performance characteristics
      of dental students and dentists using the LT in comparison to a conventional bag
      valve mask device (BVM) within manikin CPR training. METHOD: A group of eight
      dentists and 12 dental students performed randomised crossover CPR training using
      LT and BVM. Time intervals needed to perform five CPR cycles were recorded, as
      well as tidal and total gastric inflation volumes. RESULTS: Median tidal volumes
      0-1025 ml (median 462.5 ml) were observed using BVM and 100-500 ml (median 237.5
      ml) with LT (p = 0.02). Total gastric inflation of 0-2900 ml was measured using
      BVM, no gastric inflation using LT (p = 0.0005). Time intervals needed to perform
      five CPR cycles did not differ between BVM (range 87.5-354.5 s, median 112 s) and
      LT (range 84.7-322.3 s, median 114 s) (p = 0.55). A median delay of 37.6 s (range
      0-82.1 s) before starting CPR was observed using LT. CONCLUSIONS: Lower tidal
      volumes but also lower or even no gastric inflation may be observed when dentists
      use a laryngeal tube during CPR. Respective training must focus on chest
      compressions. These must be started before inserting the LT or a different
      supraglottic airway adjunct and be delivered continuously during insertion. It is
      recommended to use a supraglottic airway such as an LT only after having been
      trained in its use.

PMID- 25952456
TI  - Peripheral venous or tibial intraosseous access for medical emergency treatment
      in the dental office?
AB  - BACKGROUND: The anterior tibia has been recommended as emergency vascular access
      site if the intravenous route cannot be used. OBJECTIVE: This study aims to
      evaluate the peripheral venous and anterior tibial intraosseous puncture as
      alternatives for dentists, using a human and a cadaver model.Method One group of
      dental students performed a venipuncture by using a standard catheter device (n =
      21) on other students. Another group (n = 24) used the Vidacare EZ-IO
      intraosseous kit on a cadaver tibia with india ink as a tracer. Success rates as
      well as the time needed for a successful puncture were recorded. RESULTS: 28.5%
      of venous and 83.3% of intraosseous punctures were successful. The relative risk
      of venous cannulation failure was 3.4 (95% CI 1.6-7.2; p = 0.0005). A successful
      venous access could be performed within 163 +/- 23.2 seconds (mean +/- SD), a
      tibial intraosseous access within 30 +/- 27.8 seconds (p = 0.0003). CONCLUSIONS:
      Within the limitation of this study, it can be demonstrated that the chances to
      perform a successful vascular access for inexperienced dentists may be higher
      when using the tibial intraosseous route for emergency intravascular medication.

PMID- 25952458
TI  - Fluid absorption and the ethanol monitoring method.
AB  - BACKGROUND: Fluid absorption is a well-known complication of endoscopic
      surgeries, such as transurethral prostatic resection and transcervical
      endometrial resection. Absorption of electrolyte-free fluid in excess of 1 L,
      which occurs in 5% to 10% of the operations, markedly increases the risk of
      adverse effects from the cardiovascular and neurological systems. Absorption of
      isotonic saline, which is used with the new bipolar resection technique, will
      change the scenario of adverse effects in a yet unknown way. Hyponatremia no
      longer occurs, but marking the saline with ethanol reveals that fluid absorption
      occurs just as much as with monopolar prostate resections. METHODS: Ethanol
      monitoring is a method for non-invasive indication and quantification of fluid
      absorption that has been well evaluated. By using an irrigating fluid that
      contains 1% of ethanol, updated information about fluid absorption can be
      obtained at any time perioperatively by letting the patient breathe into a hand
      held alcolmeter. RESULTS: Regression equations and nomograms with variable
      complexity are available for estimating how much fluid has been absorbed, both
      when the alcolmeter is calibrated to show the blood ethanol level and when it is
      calibrated to show the breath ethanol concentration. Examples of how such
      estimations should be performed are given in this review article. CONCLUSIONS:
      The difficulty is that the anesthesiologist must be aware of how the alcolmeter
      is calibrated (for blood or breath) and be able to distinguish between the
      intravascular and extravascular absorption routes, which give rise to different
      patterns and levels of breath ethanol concentrations.

PMID- 25952457
TI  - Clinical and radiographic outcomes of femoral head fractures: excision vs.
      fixation of fragment in Pipkin type I: what is the optimal choice for femoral
      head fracture?
AB  - BACKGROUND: In this work, we present relatively long-term results of femoral head
      fractures with a specific focus on Pipkin type I fractures. METHODS: Fifty-nine
      femoral head fractures were treated according to modified Pipkin's classification
      as follows: type I, small fragment distal to the fovea centralis (FC); type II,
      large fragment distal to the FC; type III, large fragment proximal to the FC;
      type IV, comminuted fracture. There were 15 cases of type I, 28 of type II, 9 of
      type III, and 7 of type IV fractures. Conservative treatment with skeletal
      traction was performed in 4 type II cases, excision of the fragment in 15 type I
      and 10 type II cases, fixation of the fragment in 14 type II and all 9 type III
      cases, and total hip replacement in all 7 type IV cases. The overall clinical and
      radiographic outcomes were evaluated using previously published criteria,
      focusing on the results in Pipkin type I fractures with relatively large
      fragments. RESULTS: Based on Epstein criteria, in type II fractures, excellent or
      good clinical results were seen in 6 of 10 patients (60.0 %) treated by excision
      of the fragment and 12 of 14 patients (85.7 %) treated by internal fixation (p =
      0.05). Also, excellent or good radiologic results were seen in 4 of 10 (40.0 %)
      patients treated by excision of the fragment and 12 of 14 (85.7 %) patients
      treated by internal fixation (p = 0.03). CONCLUSIONS: Even in Pipkin type I
      fractures, if the fragment is large (modified Pipkin type II), early reduction
      and internal fixation can produce good results.

PMID- 25952459
TI  - Technological capabilities of surface layers formation on implant made of Ti-6Al
      4V ELI alloy.
AB  - PURPOSE: The aim of the presented research was to find a combination of surface
      modification methods of implants made of the Ti-6Al-4V ELI alloy, that lead to
      formation of effective barrier for metallic ions that may infiltrate into
      solution. METHODS: To this end, the following tests were carried out: roughness
      measurement, the voltamperometric tests (potentiodynamic and potentiostatic), and
      the ion infiltration test. RESULTS: The electropolishing process resulted in the
      lowering of surface roughness in comparison with mechanical treatment of the
      surface layer. The anodization process and steam sterilization increased
      corrosion resistance regardless of the mechanical treatment or electropolishing.
      The crevice corrosion tests revealed that independent of the modification method
      applied, the Ti-6Al-4V ELI alloy has excellent crevice corrosion resistance. The
      smallest quantity of ions infiltrated to the solution was observed for surface
      modification consisting in the mechanical treatment and anodization with the
      potential of 97 V. CONCLUSIONS: Electric parameters deter- mined during studies
      were the basis for effectiveness estimation of particular surface treatment
      methods. The research has shown that the anodization process significantly
      influences the pitting corrosion resistance of the Ti-6Al-4V ELI alloy
      independent of the previous surface treatment methods (mechanical and
      electrochemical). The surface layer after such modification is a protective
      barrier for metallic ions infiltrated to solution and protects titanium alloy
      against corrosive environment influence.

PMID- 25952460
TI  - Color tunable and near white-light emission of two solvent-induced 2D lead(II)
      coordination networks based on a rigid ligand 1-tetrazole-4-imidazole-benzene.
AB  - Two new lead(II) coordination polymers, [Pb(NO3)(tzib)]n (1) and [Pb(tzib)2]n
      (2), were successfully synthesized from the reaction of a rigid ligand 1
      tetrazole-4-imidazole-benzene (Htzib) and lead(II) nitrate in different solvents.
      The obtained polymers have been characterized by single-crystal X-ray diffraction
      analyses, which show that both polymers feature 2D layer structures. The
      inorganic anion nitrate in 1 shows a MU2-kappaO3:kappaO3 bridging mode to connect
      adjacent lead ions into a zigzag chain, and then the organic ligands tzib(-) join
      the neighboring chains into a 2D layer by a MU3-kappaN1:kappaN2:kappaN6
      connection mode. In 2, there are two different bridging modes of the tzib(-)
      ligand: MU3-kappaN1:kappaN2:kappaN6 and MU3-kappaN1:kappaN6 to coordinate the
      lead ions into a 2D layer structure. Interestingly, both polymers displayed
      broadband emissions covering the entire visible spectra, which could be tunable
      to near white-light emission by varying excitation wavelengths.

PMID- 25952461
TI  - Relationship between subthalamic nucleus neuronal activity and electrocorticogram
      is altered in the R6/2 mouse model of Huntington's disease.
AB  - KEY POINTS: Neural synchrony between the subthalamic nucleus (STN) and cortex is
      critical for proper information processing in basal ganglia circuits. Using in
      vivo extracellular recordings in urethane-anaesthetized mice, we demonstrate that
      single units and local field potentials from the STN exhibit oscillatory
      entrainment to low-frequency (0.5-4 Hz) rhythms when the cortex is in a
      synchronized state. Here we report novel findings in the R6/2 transgenic mouse
      model of Huntington's disease (HD) by demonstrating that STN activity is reduced
      and less phase-locked to cortical low-frequency oscillations. The spectral power
      of low-frequency oscillations in ECoG recordings of R6/2 mice is diminished while
      the spectral power of higher frequencies is augmented and such altered cortical
      patterning could lead to decreased synchrony in corticosubthalamic circuits. Our
      data establish that cortical entrainment of STN neural activity is disrupted in
      R6/2 mice and may be one of the mechanisms contributing to disordered motor
      control in HD. ABSTRACT: Huntington's disease (HD) is an autosomal dominant
      neurodegenerative disorder in which impairments in the processing of information
      between the cortex and basal ganglia are fundamental to the onset and progression
      of the HD phenotype. The corticosubthalamic hyperdirect pathway plays a pivotal
      role in motor selection and blockade of neuronal activity in the subthalamic
      nucleus (STN) results in a hyperkinetic movement syndrome, similar to the HD
      phenotype. The aim of the present study was to examine the relationship between
      neuronal activity in the STN and cortex in an animal model of HD. We performed in
      vivo extracellular recordings in the STN to measure single-unit activity and
      local field potentials in the R6/2 transgenic mouse model of HD. These recordings
      were obtained during epochs of simultaneously acquired electrocorticogram (ECoG)
      in discrete brain states representative of global cortical network
      synchronization or desynchronization. Cortically patterned STN neuronal activity
      was less phase-locked in R6/2 mice, which is likely to result in less efficient
      coding of cortical inputs by the basal ganglia. In R6/2 mice, the power of the
      ECoG in lower frequencies (0.5-4 Hz) was diminished while the power expressed in
      higher frequencies (13-100 Hz) was increased. In addition, the spontaneous
      activity of STN neurons in R6/2 mice was reduced and neurons exhibited a more
      irregular firing pattern. Glutamatergic STN neurons provide the major excitatory
      drive to the output nuclei of the basal ganglia and altered discharge patterns
      could lead to aberrant basal ganglia output and disordered motor control in HD.

PMID- 25952462
TI  - Anaphylactic reaction to patent blue V used in preoperative computed tomography
      guided dye localization of small lung nodules.

PMID- 25952463
TI  - Electrophysiological evidence of alterations to the nucleus accumbens and
      dorsolateral striatum during chronic cocaine self-administration.
AB  - As drug use becomes chronic, aberrant striatal processing contributes to the
      development of perseverative drug-taking behaviors. Two particular portions of
      the striatum, the nucleus accumbens (NAc) and the dorsolateral striatum (DLS),
      are known to undergo neurobiological changes from acute to chronic drug use.
      However, little is known about the exact progression of changes in functional
      striatal processing as drug intake persists. We sampled single-unit activity in
      the NAc and DLS throughout 24 daily sessions of chronic long-access cocaine self
      administration, and longitudinally tracked firing rates (FR) specifically during
      the operant response, an upward vertical head movement. A total of 103 neurons
      were held longitudinally and immunohistochemically localised to either NAc Medial
      Shell (n = 29), NAc Core (n = 30), or DLS (n = 54). We modeled changes
      representative of each category as a whole. Results demonstrated that FRs of DLS
      Head Movement neurons were significantly increased relative to baseline during
      all sessions, while FRs of DLS Uncategorised neurons were significantly reduced
      relative to baseline during all sessions. NAc Shell neurons' FRs were also
      significantly decreased relative to baseline during all sessions while FRs of NAc
      Core neurons were reduced relative to baseline only during training days 1-18 but
      were not significantly reduced on the remaining sessions (19-24). The data
      suggest that all striatal subregions show changes in FR during the operant
      response relative to baseline, but longitudinal changes in response firing
      patterns were observed only in the NAc Core, suggesting that this region is
      particularly susceptible to plastic changes induced by abused drugs.

PMID- 25952464
TI  - Phase II trial of gemcitabine and tanespimycin (17AAG) in metastatic pancreatic
      cancer: a Mayo Clinic Phase II Consortium study.
AB  - OBJECTIVES: Heat Shock Protein 90 (HSP90) is a molecular chaperone that
      stabilizes many oncogenic proteins. HSP90 inhibitors may sensitize tumors to
      cytotoxic agents by causing client protein degradation. Gemcitabine, which has
      modest activity in pancreas cancer, activates Chk1, a client protein of HSP90.
      This phase II trial was designed to determine whether 17AAG could enhance the
      clinical activity of gemcitabine through degradation of Chk1 in patients with
      stage IV pancreatic cancer. METHODS: A multicenter, prospective study combining
      gemcitabine and 17AAG enrolled patients with stage IV pancreatic adenocarcinoma,
      adequate liver and kidney function, ECOG performance status 0-2, and no prior
      chemotherapy for metastatic disease. The primary goal was to achieve a 60 %
      overall survival at 6 months. Sixty-six patients were planned for accrual, with
      an interim analysis after 25 patients enrolled. RESULTS: After a futility
      analysis to achieve the endpoint, accrual was halted with 21 patients enrolled.
      No complete or partial responses were seen. Forty percent of patients were alive
      at 6 months. Median overall survival was 5.4 months. Tolerability was moderate,
      with 65 % of patients having >= grade 3 adverse events (AE), and 15 % having
      grade 4 events. CONCLUSIONS: The lack of clinical activity suggests that
      targeting Chk1 by inhibiting HSP90 is not important in pancreatic cancer
      sensitivity to gemcitabine alone. Further studies of HSP90 targeted agents with
      gemcitabine alone are not warranted.

PMID- 25952465
TI  - Co-administration of antigen with chemokine MCP-3 or MDC/CCL22 enhances DNA
      vaccine potency.
AB  - We evaluated the utility of chemokine MCP-3 and MDC/CCL22 as molecular adjuvants
      of DNA vaccines for botulinum neurotoxin serotype A (BoNT/A) in a Balb/c mouse
      model. Notably, the immunogenicity of the DNA vaccine against BoNT/A was not
      enhanced using a fusion of the AHc-C antigen with the MCP-3 or MDC/CCL22.
      Nevertheless, the potency of the DNA vaccine was significantly modulated and
      enhanced by co-administration of the AHc-C antigen with MCP-3 or MDC/CCL22. This
      strategy elicited high levels of humoral immune responses and protection against
      BoNT/A. The enhanced potency was further boosted by co-administration of the AHc
      C antigen with both MCP-3 and MDC/CCL22 in Balb/c mice, but not by co
      administration of AHc-C antigen with the MCP-3-MDC/CCL22 fusion. Co-immunization
      with both the MCP-3 and MDC/CCL22 constructs induced the highest levels of
      humoral immunity and protective potency against BoNT/A. Our results indicated
      that MCP-3 and MDC/CCL22 are effective molecular adjuvants of the immune
      responses induced by the AHc-C-expressing DNA vaccine when delivered by co
      administration of the individual chemokines, but not when delivered in the form
      of a chemokine/antigen fusion. Thus, we describe an alternative strategy to the
      design and optimization of DNA vaccine constructs based on co-administration of
      the antigen with the chemokine rather than in the form of a chemokine/antigen
      fusion. 

PMID- 25952467
TI  - The DNA Bank: High-Security Bank Accounts to Protect and Share Your Genetic
      Identity.
AB  - With the cost of genome sequencing decreasing every day, DNA information has the
      potential of affecting the lives of everyone. Surprisingly, an individual has
      little knowledge about his own DNA information, can rarely access it, and has
      hardly any control over its use. This may result in preventable, life-threatening
      situations, and also significantly inhibits scientific progress. What we urgently
      need is a "DNA bank," a resource providing a secure personal account where,
      similar to a financial institution, you can store your DNA sequence. Using this
      private and secure DNA bank account, you govern your sequence-related business.
      For any genetic study performed, the data generated must be transferred (paid) to
      your DNA account. Using your account, you regulate access, knowing for what
      purpose (informed consent) and only for the genetic data you are willing to
      share. The DNA account ensures you are in the driver's seat, know what is known,
      and control what is happening with it. 

PMID- 25952466
TI  - It's all in the mime: Actions speak louder than words when teaching the cranial
      nerves.
AB  - Cranial nerve (CN) knowledge is essential for students in health professions.
      Gestures and body movements (e.g., mime) have been shown to improve cognition and
      satisfaction with anatomy teaching. The aim of this pilot study was to compare
      the effectiveness of didactic lecturing with that of miming lecturing for student
      learning of the CNs. The research design involved exposure of the same group of
      students to didactic followed by miming lecturing of CNs. The effectiveness of
      each lecturing strategy was measured via pre- and post-testing. Student
      perceptions of these strategies were measured by a survey. As an example of
      miming, gestures for CN VII included funny faces for muscles of facial
      expression, kangaroo vocalization for taste, spitting action for saliva
      production, and crying for lacrimal gland production. Accounting for extra
      duration of the miming lecture, it was shown that pre- to post-test improvement
      was higher for the miming presentation than for the didactic (0.47 +/- 0.03
      marks/minute versus 0.33 +/- 0.03, n = 39, P < 0.005). Students perceived that
      the miming lecture was more interactive, engaging, effective, and motivating to
      attend (mean on five-point Likert scale: 4.62, 4.64, 4.56, 4.31, respectively)
      than the didactic lecture. In the final examination, performance was better (P <
      0.001, n = 39) on the CN than on the non-CN questions-particularly for students
      scoring <=60%. While mediating factors need elucidation (e.g., learning due to
      repetition of content), this study's findings support the theory that gestures
      and body movements help learners to acquire anatomical knowledge.

PMID- 25952469
TI  - ISFEV 2014: Environmental, Food and Health Impacts of Enteric Viruses.

PMID- 25952468
TI  - [Formula: see text]Intellectual and adaptive functioning in Sturge-Weber
      Syndrome.
AB  - The present study examined the intellectual and adaptive functioning in a sample
      of children and young adults with Sturge-Weber Syndrome (SWS). A total of 80
      research participants from a SWS study database underwent full neurological
      evaluation as part of their participation or concurrent medical care. Twenty-nine
      of the participants received neuropsychological evaluations. Analyses indicated
      no significant demographic or neurological differences between those who did and
      did not receive neuropsychological evaluations. Overall, the neuropsychological
      evaluation sample displayed significantly lower functioning relative to published
      normative data across domains of intellectual and adaptive functioning. Thirty
      two percent of the sample displayed impaired performance (standard score <= 75)
      in intellectual functioning and 58% displayed impaired performance in adaptive
      functioning. Hemiparesis status independently predicted overall adaptive
      functioning while seizure frequency independently predicted overall intellectual
      functioning. Younger participants displayed significantly higher (more intact)
      ratings in adaptive functioning compared to older participants, specifically in
      overall adaptive functioning, motor skills, and community living skills. A
      composite measure of neurological status (SWS-NRS) incorporating seizure and
      hemiparesis status effectively distinguished between individuals with impaired or
      nonimpaired adaptive and intellectual functioning and showed promise as a
      screening method for identifying individuals with more involved intellectual
      and/or adaptive needs.

PMID- 25952470
TI  - Serum 25-Hydroxyvitamin D Levels: Variability, Knowledge Gaps, and the Concept of
      a Desirable Range.
AB  - Hypovitaminosis D is prevalent worldwide but proportions vary widely between
      regions, depending on genetic and lifestyle factors, the threshold to define
      deficiency, and accuracy of 25-hydroxyvitamin D (25OHD) assays used. Latitude,
      pollution, concealing clothing, sun exposure, gender, dietary habits, and lack of
      government regulation account for up to 50% in variations in serum 25OHD levels,
      whereas genetic polymorphisms in the vitamin D pathway account for less than 5%.
      Organizations/societies have developed guidelines for recommended desirable 25OHD
      levels and vitamin D doses to reach them, but their applicability across age
      groups and populations are still debated. This article and the accompanying
      online Supporting Information highlight sources of variations in circulating
      25OHD levels, uncertainties and knowledge gaps, and analytical problems facing
      25OHD assays, while keeping efficacy and safety data as the dominant factors when
      defining a desirable range for 25OHD levels. We propose a desirable range of 20
      to 40 ng/mL (50 to 100 nmol/L), provided precise and accurate assays are used.
      Although slightly lower levels, 15 to 20 ng/mL, may be sufficient for some
      infants and adults, higher levels, 40 to 60 ng/mL, may still be safe. This
      desirable range allows physicians to tailor treatment while taking season,
      lifestyle, vitamin D intake, and other sources of variation into account. We
      reserve 25OHD measurements for at-risk patients, defined by disease or lifestyle,
      and the use of 25OHD assays calibrated against the recommended international
      standards. Most target groups reach desirable target levels by a daily intake of
      400 to 600 IU for children and 800 IU for adults. A total daily allowance of
      vitamin D of up to 1000 IU in the pediatric age groups, and up to 2000 IU in
      adults, tailored to an individual patient risk profile, is probably safe over
      long durations. Additional data are needed to validate the proposed range and
      vitamin D doses, especially in children, pregnant women, and non-white
      populations.

PMID- 25952473
TI  - The ABCs of clinical measures.

PMID- 25952471
TI  - A centralized cardiovascular risk service to improve guideline adherence in
      private primary care offices.
AB  - BACKGROUND: Many large health systems now employ clinical pharmacists in team
      based care to assist patients and physicians with management of cardiovascular
      (CV) diseases. However, small private offices often lack the resources to hire a
      clinical pharmacist for their office. The purpose of this study is to evaluate
      whether a centralized, web-based CV risk service (CVRS) managed by clinical
      pharmacists will improve guideline adherence in primary care medical offices in
      rural and small communities. METHODS: This study is a cluster randomized
      prospective trial in 12 primary care offices. Medical offices were randomized to
      either the CVRS intervention or usual care. The intervention will last for 12
      months and all subjects will have research visits at baseline and 12 months.
      Primary outcomes will include adherence to treatment guidelines and control of
      key CV risk factors. Data will also be abstracted from the medical record at 30
      months to determine if the intervention effect is sustained after it is
      discontinued. CONCLUSIONS: This study will enroll subjects through 2015 and
      results will be available in 2018. This study will provide information on whether
      a distant, centralized CV risk service can improve guideline adherence in medical
      offices that lack the resources to employ clinical pharmacists.

PMID- 25952474
TI  - A non-cross-coupling approach to arene-bridged macrocycles: synthesis, structure,
      and direct, regioselective functionalization of a cycloparaphenylene fragment.
AB  - A new synthetic strategy that employs a relatively unstrained, 1,4-diketo-bridged
      macrocycle as a precursor to a strained, 1,4-arene-bridged (bent para-phenylene)
      macrocycle has been developed. The distorted p-terphenyl nucleus (CPP fragment)
      of the macrocycle has been characterized by X-ray crystallography, and a direct,
      regioselective bromination protocol of the macrocyclic system is reported. 

PMID- 25952472
TI  - Investigating the pharmacokinetics and biological distribution of silver-loaded
      polyphosphoester-based nanoparticles using (111) Ag as a radiotracer.
AB  - Purified (111) Ag was used as a radiotracer to investigate silver loading and
      release, pharmacokinetics, and biodistribution of polyphosphoester-based
      degradable shell crosslinked knedel-like (SCK) nanoparticles as a comparison to
      the previously reported small molecule, N-heterocyclic silver carbene complex
      analog (SCC1) for the delivery of therapeutic silver ions in mouse models.
      Biodistribution studies were conducted by aerosol administration of (111) Ag
      acetate, [(111) Ag]SCC1, and [(111) Ag]SCK doses directly into the lungs of
      C57BL/6 mice. Nebulization of the (111) Ag antimicrobials resulted in an average
      uptake of 1.07 +/- 0.12% of the total aerosolized dose given per mouse. The
      average dose taken into the lungs of mice was estimated to be 2.6 +/- 0.3% of the
      dose inhaled per mouse for [(111) Ag]SCC1 and twice as much dose was observed for
      the [(111) Ag]SCKs (5.0 +/- 0.3% and 5.9 +/- 0.8% for [(111) Ag]aSCK and [(111)
      Ag]zSCK, respectively) at 1 h post administration (p.a.). [(111) Ag]SCKs also
      exhibited higher dose retention in the lungs; 62-68% for [(111) Ag]SCKs and 43%
      for [(111) Ag]SCC1 of the initial 1 h dose were observed in the lungs at 24 h
      p.a.. This study demonstrates the utility of (111) Ag as a useful tool for
      monitoring the pharmacokinetics of silver-loaded antimicrobials in vivo. 

PMID- 25952475
TI  - A Frailty Index Based on Common Laboratory Tests in Comparison With a Clinical
      Frailty Index for Older Adults in Long-Term Care Facilities.
AB  - INTRODUCTION: Easily employed measures of frailty are needed in the evaluation of
      elderly people. Recently, a frailty index (FI) based on deficits in commonly used
      laboratory tests (the FI-LAB) has been proposed. To address the usefulness of the
      FI-LAB in long-term care (LTC) settings, we studied institutionalized
      participants in the Canadian Study of Health and Aging first clinical examination
      database. Our objectives were to compare the FI-LAB with a clinical FI LTC (FI
      Clinical-LTC) focused on common health deficits seen in LTC and to assay its
      relationship with mortality. METHODS: In this secondary analysis, Canadian Study
      of Health and Aging first clinical examination participants who, at baseline,
      were LTC residents, and who consented to having blood drawn for 21 commonly
      employed laboratory tests (eg, complete blood count, electrolytes, renal,
      thyroid, and liver function) were studied. A 23-item FI-LAB was constructed based
      on the 21 laboratory tests, plus measures of systolic and diastolic blood
      pressure. The FI-Clinical-LTC was constructed from data obtained during the
      clinical evaluation and the FI-LAB was constructed from laboratory data plus
      systolic and diastolic blood pressure measurements. A combined FI (FI-Combined)
      included all items from each index. Predictive validity was tested using Cox
      proportional hazards analysis and overall utility was evaluated using the Akaike
      Information Criterion and the Wald statistic. RESULTS: The mean FI-Clinical-LTC
      was 0.32 +/- 0.14, the FI-LAB was 0.26 +/- 0.11 and the FI-Combined was 0.30 +/-
      0.11. There was a strong linear relationship (Pearson correlation coefficient =
      0.95) between the FI-LAB and the FI-Clinical-LTC, with a significant slope of
      0.18 (P value of <.0001). Strong relationships with mortality were demonstrated
      through Kaplan-Meier curves and Cox regressions, with the FI-Clinical-LTC having
      a hazard ratio of 1.03, FI-LAB ratio of 1.02, and FI-combined ratio of 1.04 for
      each 0.01 increment in the corresponding FI in age and sex adjusted models.
      CONCLUSIONS: An FI based on routinely collected laboratory data can identify LTC
      residents at increased risk of death. This approach may be a useful screening
      tool in this setting.

PMID- 25952476
TI  - The inclusion of open-ended questions on quantitative surveys of children:
      Dealing with unanticipated responses relating to child abuse and neglect.
AB  - Web surveys have been shown to be a viable, and relatively inexpensive, method of
      data collection with children. For this reason, the Kids' Life and Times (KLT)
      was developed as an annual online survey of 10 and 11 year old children. Each
      year, approximately 4,000 children participate in the survey. Throughout the six
      years that KLT has been running, a range of questions has been asked that are
      both policy-relevant and important to the lives of children. Given the method
      employed by the survey, no extremely sensitive questions that might cause the
      children distress are included. The majority of questions on KLT are closed
      yielding quantitative data that are analysed statistically; however, one regular
      open-ended question is included at the end of KLT each year so that the children
      can suggest questions that they think should be asked on the survey the following
      year. While most of the responses are innocuous, each year a small minority of
      children suggest questions on child abuse and neglect. This paper reports the
      responses to this question and reflects on how researchers can, and should, deal
      with this issue from both a methodological and an ethical perspective. 

PMID- 25952477
TI  - Has upwelling strengthened along worldwide coasts over 1982-2010?
AB  - Changes in coastal upwelling strength have been widely studied since 1990 when
      Bakun proposed that global warming can induce the intensification of upwelling in
      coastal areas. Whether present wind trends support this hypothesis remains
      controversial, as results of previous studies seem to depend on the study area,
      the length of the time series, the season, and even the database used. In this
      study, temporal and spatial trends in the coastal upwelling regime worldwide were
      investigated during upwelling seasons from 1982 to 2010 using a single wind
      database (Climate Forecast System Reanalysis) with high spatial resolution (0.3
      degrees ). Of the major upwelling systems, increasing trends were only observed
      in the coastal areas of Benguela, Peru, Canary, and northern California. A
      tendency for an increase in upwelling-favourable winds was also identified along
      several less studied regions, such as the western Australian and southern
      Caribbean coasts. 

PMID- 25952478
TI  - Mental subtraction and multiplication recruit both phonological and visuospatial
      resources: evidence from a symmetric dual-task design.
AB  - Previous studies pointed out a selective interaction between different working
      memory subsystems (i.e., phonological and visuospatial) and arithmetic operations
      (i.e., multiplication and subtraction). This was interpreted to support the idea
      that multiplication and subtraction predominantly rely on a phonologically or
      spatially organized number code, respectively. Here, we investigated this idea in
      two groups (multiplication and subtraction group) using a dual-task paradigm.
      Going beyond previous studies, we carefully controlled and balanced the
      difficulty of both working memory and calculation tasks within and across
      participants. This allowed us to test the reciprocal impact of calculations on
      working memory. We observed no selective interaction between different working
      memory subsystems and arithmetic operations. Instead, both types of arithmetic
      operations were impaired by both types of concurrent working memory tasks.
      Likewise, both types of working memory tasks were impaired by both types of
      concurrent arithmetic. Our findings suggest that multiplication and subtraction
      depend on both phonological and visuospatial codes and highlight the importance
      of balancing task demands within and between participants in the context of dual
      task studies. 

PMID- 25952481
TI  - The erosion of physical activity in Western societies: an economic death march.
AB  - By 2030 type 2 diabetes and associated complications will be the seventh leading
      cause of death globally. In this context, obesity and physical inactivity have
      emerged as major risk factors for several chronic metabolic disorders. While
      exercise training exerts numerous health-related benefits in terms of the
      prevention and treatment of many disease states, including type 2 diabetes, it is
      currently under-prescribed and under-valued. We contend that unless urgent action
      is taken to curb the tidal wave of inactivity-related metabolic diseases, the
      worldwide economic burden associated with the rise in the number of diagnosed
      cases of type 2 diabetes will trigger the start of an economic death march for
      both industrial and developing nations alike. In this commentary we look ahead to
      2065 and consider the impact that lifestyle interventions and associated
      strategies are likely to have in curbing the epidemic tide of type 2 diabetes.
      This is one of a series of commentaries under the banner '50 years forward',
      giving personal opinions on future perspectives in diabetes, to celebrate the
      50th anniversary of Diabetologia (1965-2015).

PMID- 25952480
TI  - A proposal for the use of uniform diagnostic criteria for gestational diabetes in
      Europe: an opinion paper by the European Board & College of Obstetrics and
      Gynaecology (EBCOG).
AB  - Screening and diagnostic criteria for gestational diabetes (GDM) are inconsistent
      across Europe, and the development of a uniform GDM screening strategy is
      necessary. Such a strategy would create opportunities for more women to receive
      timely treatment for GDM. Developing a consensus on screening for GDM in Europe
      is challenging, as populations are diverse and healthcare delivery systems also
      differ. The European Board & College of Obstetrics and Gynaecology (EBCOG) has
      responded to this challenge by appointing a steering committee, including members
      of the EBCOG and the Diabetic Pregnancy Study Group (DPSG) associated with the
      EASD, to develop a proposal for the use of uniform diagnostic criteria for GDM in
      Europe. A proposal has been developed and has now been approved by the Council of
      the EBCOG. The current proposal is to screen for overt diabetes at the first
      prenatal contact using cut-off values for diabetes outside pregnancy, with
      particular efforts made to screen high-risk groups. When screening for GDM is
      performed at 24 weeks' gestation or later, the proposal is now to use the 75 g
      OGTT with the new WHO diagnostic criteria for GDM. However, more research is
      necessary to evaluate the best GDM screening strategy for different populations
      in Europe. Therefore, no clear recommendation has been made on whether a
      universal one-step, two-step or a risk-factor-based screening approach should be
      used. The use of the same WHO diagnostic GDM criteria across Europe will be an
      important step towards uniformity.

PMID- 25952479
TI  - The receptor CD44 is associated with systemic insulin resistance and
      proinflammatory macrophages in human adipose tissue.
AB  - AIMS/HYPOTHESIS: Proinflammatory immune cell infiltration in human adipose tissue
      is associated with the development of insulin resistance. We previously
      identified, via a gene expression-based genome-wide association study, the cell
      surface immune cell receptor CD44 as a functionally important gene associated
      with type 2 diabetes. We then showed that, compared with controls, Cd44 knockout
      mice were protected from insulin resistance and adipose tissue inflammation
      during diet-induced obesity. We thus sought to test whether CD44 is associated
      with adipose tissue inflammation and insulin resistance in humans. METHODS:
      Participants included 58 healthy, overweight/moderately obese white adults who
      met predetermined criteria for insulin resistance or insulin sensitivity based on
      the modified insulin-suppression test. Serum was collected from 43 participants
      to measure circulating concentrations of CD44. Subcutaneous adipose tissue was
      obtained from 17 participants to compare CD44, its ligand osteopontin (OPN, also
      known as SPP1) and pro-inflammatory gene expression. CD44 expression on adipose
      tissue macrophage (ATM) surfaces was determined by flow cytometry. RESULTS: Serum
      CD44 concentrations were significantly increased in insulin-resistant (IR)
      participants. CD44 gene expression in subcutaneous adipose tissue was threefold
      higher in the IR subgroup. The expression of OPN, CD68 and IL6 was also
      significantly elevated in IR individuals. CD44 gene expression correlated
      significantly with CD68 and IL6 expression. CD44 density on ATMs was associated
      with proinflammatory M1 polarisation. CONCLUSIONS/INTERPRETATION: CD44 and OPN in
      human adipose tissue are associated with localised inflammation and systemic
      insulin resistance. This receptor-ligand pair is worthy of further research as a
      potentially modifiable contributor to human insulin resistance and type 2
      diabetes.

PMID- 25952482
TI  - Comparison of double-locus sequence typing (DLST) and multilocus sequence typing
      (MLST) for the investigation of Pseudomonas aeruginosa populations.
AB  - Reliable molecular typing methods are necessary to investigate the epidemiology
      of bacterial pathogens. Reference methods such as multilocus sequence typing
      (MLST) and pulsed-field gel electrophoresis (PFGE) are costly and time consuming.
      Here, we compared our newly developed double-locus sequence typing (DLST) method
      for Pseudomonas aeruginosa to MLST and PFGE on a collection of 281 isolates. DLST
      was as discriminatory as MLST and was able to recognize "high-risk" epidemic
      clones. Both methods were highly congruent. Not surprisingly, a higher
      discriminatory power was observed with PFGE. In conclusion, being a simple method
      (single-strand sequencing of only 2 loci), DLST is valuable as a first-line
      typing tool for epidemiological investigations of P. aeruginosa. Coupled to a
      more discriminant method like PFGE or whole genome sequencing, it might represent
      an efficient typing strategy to investigate or prevent outbreaks. 

PMID- 25952483
TI  - A population-based study of the risk of schizophrenia and bipolar disorder
      associated with parent-child separation during development.
AB  - BACKGROUND: There is growing interest in the role of childhood adversities,
      including parental death and separation, in the etiology of psychotic disorders.
      However, few studies have used prospectively collected data to specifically
      investigate parental separation across development, or assessed the importance of
      duration of separation, and family characteristics. METHOD: We measured three
      types of separation not due to death: maternal, paternal, and from both parents,
      across the ages of 1-15 years among a cohort of 985 058 individuals born in
      Denmark 1971-1991 and followed to 2011. Associations with narrowly and broadly
      defined schizophrenia and bipolar disorder in the psychiatric register were
      assessed in terms of separation occurrence, age of separation, and number of
      years separated. Interactions with parental history of mental disorder were
      assessed. RESULTS: Each type of separation was associated with all three
      outcomes, adjusting for age, sex, birth period, calendar year, family history of
      mental disorder, urbanicity at birth and parental age. Number of years of
      paternal separation was positively associated with both schizophrenia and bipolar
      disorder. Associations between separation from both parents and schizophrenia
      were stronger when separation occurred at later ages, while those with bipolar
      disorder remained stable across development. The first occurrence of paternal
      separation appeared to increase risk more when it occurred earlier in childhood.
      Associations differed according to parental history of mental disorder, although
      in no situation was separation protective. CONCLUSIONS: Effects of parental
      separation may differ by type, developmental timing and family characteristics.
      These findings highlight the importance of considering such factors in studies of
      childhood adversity.

PMID- 25952484
TI  - Surviving surveillance.

PMID- 25952485
TI  - Optimal post-treatment surveillance in cancer survivors: is more really better?
AB  - A substantial rise in the number of cancer survivors has led to management
      questions regarding effective post-treatment surveillance strategies. Although a
      number of professional societies have proposed surveillance guidelines, clinical
      practice varies; the general trend is toward more intensive strategies. The
      evidence supporting intensive surveillance is relatively lacking, with most
      studies showing that more intense surveillance regimens have minimal, if any,
      impact on outcomes in terms of survival, quality of life, or overall cost
      effectiveness. This has been demonstrated in breast cancer, and data supporting a
      similar conclusion may be evolving in colorectal cancer, where large prospective
      studies call into question the utility of intensive surveillance; in prostate
      cancer, retrospective data suggest a similar trend. In this review, we discuss
      the established guidelines and current evidence regarding post-treatment
      surveillance, and we propose general management strategies in prostate,
      colorectal, and breast cancers. 

PMID- 25952486
TI  - Caring for the life you saved.

PMID- 25952487
TI  - Current and emerging treatments for brain metastases.
AB  - Brain metastasis in patients with cancer can be indicative of multisystem spread
      or lead to neurological demise if not locally controlled, and is associated with
      poor survival and high morbidity. Compared with metastasis to other areas of the
      body, brain metastasis possesses a unique biology that confers high resistance to
      systemic therapies. This phenomenon has been historically attributed to the
      inability of chemotherapeutic agents to pass through the blood-brain barrier.
      Recent studies challenge this premise, revealing other potentially targetable
      mechanism(s). Therapies that exploit recent advances in the understanding of
      brain metastasis are still in early stages of development. Encouragingly, and
      discovered by happenstance, some molecularly targeted drugs already appear to
      have efficacy against certain tumors and accompanying cerebral edema. In the
      meantime, conventional treatment modalities such as surgery and radiation have
      iteratively reached new levels of refinement. However, these achievements are
      somewhat muted by the emergence of magnetic resonance (MR)-guided laser
      interstitial thermal therapy, a minimally invasive neuroablative technique. On
      the horizon, MR-guided focused ultrasound surgery is similarly intriguing. Even
      in the absence of further advances, local control is frequently achieved with
      state-of-the-art therapies. Dramatic improvements will likely require
      sophisticated approaches that account for the particular effects of the
      microenvironment of the central nervous system on metastasis. 

PMID- 25952488
TI  - Brain metastases: the changing landscape.

PMID- 25952489
TI  - Management of brain metastases in the era of targeted and immunomodulatory
      therapies.

PMID- 25952490
TI  - Treating anaplastic oligodendrogliomas and WHO grade 2 gliomas: PCV or
      temozolomide? The case for PCV.

PMID- 25952491
TI  - Treating anaplastic oligodendrogliomas and WHO grade 2 gliomas: PCV or
      temozolomide? The case for temozolomide.

PMID- 25952493
TI  - Treating chemotherapy-induced thrombocytopenia: is it time for oncologists to use
      thrombopoietin agonists?

PMID- 25952492
TI  - Managing thrombocytopenia associated with cancer chemotherapy.
AB  - Thrombocytopenia is a common problem in cancer patients. Aside from bleeding
      risk, thrombocytopenia limits chemotherapy dose and frequency. In evaluating
      thrombocytopenic cancer patients, it is important to assess for other causes of
      thrombocytopenia, including immune thrombocytopenia, coagulopathy, infection,
      drug reaction, post-transfusion purpura, and thrombotic microangiopathy. The
      incidence of chemotherapy-induced thrombocytopenia varies greatly depending on
      the treatment used; the highest rates of this condition are associated with
      gemcitabine- and platinum-based regimens. Each chemotherapy agent differs in how
      it causes thrombocytopenia: alkylating agents affect stem cells, cyclophosphamide
      affects later megakaryocyte progenitors, bortezomib prevents platelet release
      from megakaryocytes, and some treatments promote platelet apoptosis.
      Thrombopoietin is the main regulator of platelet production. In numerous studies,
      recombinant thrombopoietin raised the platelet count nadir, reduced the need for
      platelet transfusions, reduced the duration of thrombocytopenia, and allowed
      maintenance of chemotherapy dose intensity. Two thrombopoietin receptor agonists
      now available, romiplostim and eltrombopag, are potent stimulators of platelet
      production. Although few studies have been completed to demonstrate their ability
      to treat chemotherapy-induced thrombocytopenia, these agents may be useful in
      treating this condition in some situations. Chemotherapy dose reduction and
      platelet transfusions remain the major treatments for affected patients. 

PMID- 25952494
TI  - Thrombocytopenia: optimizing approaches in cancer patients.

PMID- 25952495
TI  - Medication Routines and Adherence Among Hypertensive African Americans.
AB  - Poor adherence to prescribed medication regimens remains an important challenge
      preventing successful treatment of cardiovascular diseases such as hypertension.
      While studies have documented differences in the time of day or weekday vs
      weekend on medication adherence, no study has examined whether having a
      medication-taking routine contributes to increased medication adherence. The
      purpose of this study was to: (1) identify patients' sociodemographic factors
      associated with consistent medication-taking routine; (2) examine associations
      between medication-taking consistency, medication adherence, and blood pressure
      (BP) control. The study included black patients with hypertension (n = 190; 22
      men and 168 women; age, mean+/-standard deviation 54 +/- 12.08 years) who
      completed a practice-based randomized controlled trial. Findings showed that
      medication-taking consistency was significantly associated with better medication
      adherence (F = 9.54, P = .002). Associations with the consistency index were not
      statistically significant for diastolic BP control (odds ratio, 1.319; 95%
      confidence interval, 0.410-4.246; P = .642) and systolic BP control (odds ratio,
      0.621; 95% confidence interval, 0.195-1.974; P = .419). 

PMID- 25952496
TI  - A novel multiplex RT-qPCR method based on dual-labelled probes suitable for
      typing all known genotypes of viral haemorrhagic septicaemia virus.
AB  - Viral haemorrhagic septicaemia (VHS) is a notifiable fish disease, whose
      causative agent is a rhabdovirus isolated from a wide range of fish species, not
      only in fresh but also in marine and brackish waters. Phylogenetic studies have
      identified four major genotypes, with a strong geographical relationship. In this
      study, we have designed and validated a new procedure--named binary multiplex RT
      qPCR (bmRT-qPCR)--for simultaneous detection and typing of all four genotypes of
      VHSV by real-time RT-PCR based on dual-labelled probes and composed by two
      multiplex systems designed for European and American/Asiatic isolates,
      respectively, using a combination of three different fluorophores. The
      specificity of the procedure was assessed by including a panel of 81 VHSV
      isolates covering all known genotypes and subtypes of the virus, and tissue
      material from experimentally infected rainbow trout, resulting in a correct
      detection and typing of all strains. The analytical sensitivity was evaluated in
      a comparative assay with titration in cell culture, observing that both methods
      provided similar limits of detection. The proposed method can be a powerful tool
      for epidemiological analysis of VHSV by genotyping unknown samples within a few
      hours.

PMID- 25952497
TI  - Modulating the inflammatory response to provide the best environment for healing
      in the pelvic organ prolapse (POP) repair. A preliminary study using coated
      medical devices.
AB  - AIM: We studied the inflammatory response in Phosphorylcholine (PC)-coated and
      uncoated meshes after 4 weeks of implantation in the subcutaneous tissue of the
      hypogastric region in six patients. MATERIAL AND METHODS: Six patients underwent
      POP surgery using two different types of mesh. In three of them a PC-coated mesh
      was implanted and an uncoated one was implanted in the last three. A small part
      of the mesh has previously been cut with a standard size decided by the authors
      and was subsequently implanted in the same time of the pop repair in the
      subcutaneous fascia of the hypogastric region. After 4 weeks the small part of
      the mesh was explanted and tissue growth in the fishnet-like mesh was analyzed.
      RESULTS: A typical foreign body response formed around the uncoated meshes. On
      the other hand there was a lack in the inflammatory response around the PC-coated
      mesh identifying less histiocytes, less giant cells and a thinner fibrous capsule
      formation. DISCUSSION: PC polymers have demonstrated excellent biocompatibility
      and hemocompatibility. The adsorption of protein onto materials' surface and the
      trauma involved in surgery necessary for device implantation determines an
      inflammatory response. The ability of the PC coating to reduce the extent of
      nonspecific proteins, modulates the specific environment around the implant.
      CONCLUSION: This preliminary study showed that modulating the inflammatory
      response we attempt to provide the best environment for healing.

PMID- 25952498
TI  - A method of searching for related literature on protein structure analysis by
      considering a user's intention.
AB  - BACKGROUND: In recent years, with advances in techniques for protein structure
      analysis, the knowledge about protein structure and function has been published
      in a vast number of articles. A method to search for specific publications from
      such a large pool of articles is needed. In this paper, we propose a method to
      search for related articles on protein structure analysis by using an article
      itself as a query. RESULTS: Each article is represented as a set of concepts in
      the proposed method. Then, by using similarities among concepts formulated from
      databases such as Gene Ontology, similarities between articles are evaluated. In
      this framework, the desired search results vary depending on the user's search
      intention because a variety of information is included in a single article.
      Therefore, the proposed method provides not only one input article (primary
      article) but also additional articles related to it as an input query to
      determine the search intention of the user, based on the relationship between two
      query articles. In other words, based on the concepts contained in the input
      article and additional articles, we actualize a relevant literature search that
      considers user intention by varying the degree of attention given to each concept
      and modifying the concept hierarchy graph. CONCLUSIONS: We performed an
      experiment to retrieve relevant papers from articles on protein structure
      analysis registered in the Protein Data Bank by using three query datasets. The
      experimental results yielded search results with better accuracy than when user
      intention was not considered, confirming the effectiveness of the proposed
      method.

PMID- 25952499
TI  - Multiple myeloma and bone.

PMID- 25952500
TI  - Transglutaminase 2 expressed in mast cells recruited into skin or bone marrow
      induces the development of pediatric mastocytosis.
AB  - BACKGROUND: Mastocytosis is characterized by a pathological increase in mast
      cells in organs such as skin and bone marrow. Transglutaminase 2 (TG2) expressed
      in mast cells contributes to allergic diseases, but its role in mastocytosis has
      not been investigated. This study aimed to investigate whether TG2 contributes to
      pediatric mastocytosis. METHODS: Serum, various skin tissues or bone marrow (BM)
      biopsy and aspirates were obtained from pediatric normal control or patients with
      indolent systemic mastocytosis (SM), mastocytoma, and urticaria pigmentosa (UP).
      Tryptase, individual cytokines, leukotriene C4 (LTC4 ), and TG2 activity in the
      serum were determined by enzyme-linked immunosorbent assay, mast cell population
      by May-Grunwald-Giemsa, CD 117 by immunofluorescence, cell surface molecules by
      Western blot, and colocalization of c-kit and TG2 or IL-10-expressing cells,
      CD25, and FOXP3 by immunohistochemistry. RESULTS: Infiltration of CD25(+)
      CD117(+) CD2(-) mast cells into BM and scalp/trunk/ear dermis; expression of
      FcepsilonRI, tryptase, c-kit, FOXP3, CCL2/CCR2, and vascular cell adhesion
      molecule-1; and colocalization of c-kit and TG2 were enhanced in patient's skin
      tissues or BM, particularly SM, but colocalization of c-kit and IL-10-expressing
      cells was decreased vs. normal tissues. Amounts of LTC4 and inflammatory
      cytokines, expression of tryptase or TG2 activity were increased in patient's
      serum, BM aspirates, or ear/scalp skin tissues, respectively, vs. normal persons,
      but IL-10 level was decreased. CONCLUSION: The data suggest that mast cells,
      recruited in the skin and BM by CCL2/CCR, may induce the development of pediatric
      mastocytosis through reducing IL-10 due to upregulating TG2 activity via
      transcription factor nuclear factor-kappaB. Thus, TG2 may be used in diagnosis of
      pediatric mastocytosis, particularly SM.

PMID- 25952501
TI  - A magnonic gas sensor based on magnetic nanoparticles.
AB  - In this paper, we propose an innovative, simple and inexpensive gas sensor based
      on the variation in the magnetic properties of nanoparticles due to their
      interaction with gases. To measure the nanoparticle response a magnetostatic spin
      wave (MSW) tunable oscillator has been developed using an yttrium iron garnet
      (YIG) epitaxial thin film as a delay line (DL). The sensor has been prepared by
      coating a uniform layer of CuFe2O4 nanoparticles on the YIG film. The unperturbed
      frequency of the oscillator is determined by a bias magnetic field, which is
      applied parallel to the YIG film and perpendicularly to the wave propagation
      direction. In this device, the total bias magnetic field is the superposition of
      the field of a permanent magnet and the field associated with the layer of
      magnetic nanoparticles. The perturbation produced in the magnetic properties of
      the nanoparticle layer due to its interaction with gases induces a frequency
      shift in the oscillator, allowing the detection of low concentrations of gases.
      In order to demonstrate the ability of the sensor to detect gases, it has been
      tested with organic volatile compounds (VOCs) which have harmful effects on human
      health, such as dimethylformamide, isopropanol and ethanol, or the aromatic
      hydrocarbons like benzene, toluene and xylene more commonly known by its
      abbreviation (BTX). All of these were detected with high sensitivity, short
      response time, and good reproducibility. 

PMID- 25952502
TI  - Re: Emotions, immunity and sport: Winner and loser athlete's profile of fighting
      sport.

PMID- 25952504
TI  - The copper-catalyzed asymmetric construction of a dispiropyrrolidine skeleton via
      1,3-dipolar cycloaddition of azomethine ylides to alpha-alkylidene succinimides.
AB  - A highly efficient asymmetric 1,3-dipolar cycloaddition of azomethine ylides to
      alpha-alkylidene succinimides catalyzed by a novel chiral N,O-ligand/Cu(OAc)2
      system is reported, affording dispiropyrrolidine derivatives with spiro
      quaternary stereogenic centers in good to excellent yields (up to 90%), excellent
      levels of diastereoselectivities (>20 : 1 dr) and enantioselectivities (up to 97%
      ee). 

PMID- 25952503
TI  - Opioid Prescribing in a Cross Section of US Emergency Departments.
AB  - STUDY OBJECTIVE: Opioid pain reliever prescribing at emergency department (ED)
      discharge has increased in the past decade but specific prescription details are
      lacking. Previous ED opioid pain reliever prescribing estimates relied on
      national survey extrapolation or prescription databases. The main goal of this
      study is to use a research consortium to analyze the characteristics of patients
      and opioid prescriptions, using a national sample of ED patients. We also aim to
      examine the indications for opioid pain reliever prescribing, characteristics of
      opioids prescribed both in the ED and at discharge, and characteristics of
      patients who received opioid pain relievers compared with those who did not.
      METHODS: This observational, multicenter, retrospective, cohort study assessed
      opioid pain reliever prescribing to consecutive patients presenting to the
      consortium EDs during 1 week in October 2012. The consortium study sites
      consisted of 19 EDs representing 1.4 million annual visits, varied
      geographically, and were predominantly academic centers. Medical records of all
      patients aged 18 to 90 years and discharged with an opioid pain reliever
      (excluding tramadol) were individually abstracted by standardized chart review by
      investigators for detailed analysis. Descriptive statistics were generated.
      RESULTS: During the study week, 27,516 patient visits were evaluated in the
      consortium EDs; 19,321 patients (70.2%) were discharged and 3,284 (11.9% of all
      patients and 17.0% of discharged patients) received an opioid pain reliever
      prescription. For patients prescribed an opioid pain reliever, mean age was 41
      years (SD 14 years) and 1,694 (51.6%) were women. Mean initial pain score was 7.7
      (SD 2.4). The most common diagnoses associated with opioid pain reliever
      prescribing were back pain (10.2%), abdominal pain (10.1%), and extremity
      fracture (7.1%) or sprain (6.5%). The most common opioid pain relievers
      prescribed were oxycodone (52.3%), hydrocodone (40.9%), and codeine (4.8%).
      Greater than 99% of pain relievers were immediate release and 90.0% were
      combination preparations, and the mean and median number of pills was 16.6 (SD
      7.6) and 15 (interquartile range 12 to 20), respectively. CONCLUSION: In a study
      of ED patients treated during a single week across the country, 17% of discharged
      patients were prescribed opioid pain relievers. The majority of the prescriptions
      had small pill counts and almost exclusively immediate-release formulations.

PMID- 25952505
TI  - Cryoablation induced the change of TGF-beta pathway in CWR-22RV prostate cancer
      cell line.
AB  - PURPOSE: To assess the efficacy of TGF-beta pathway in the CWR-22RV prostate
      cancer cell line induced by cryoablation. MATERIALS AND METHODS: According to the
      district in the tumor following cryoablation, the CWR-22RV prostate cancer cells
      were divided into four groups to construct the freezing model of prostate cancer
      in cell level: Group A, control cells (the uncovered district), Group B, freezing
      cells (sub-lethal district away from necrosis), Group C, control cells cultured
      with 1640 and necrosis supernatant and Group D, freezing cells cultured with 1640
      and necrosis supernatant (sub-lethal district close to necrosis). Cell apoptosis
      was observed by flow cytometry analysis 24 h later. Then supernatant in four
      groups was extracted to test the concentration of TGF-beta by ELISA at the time
      points of 5, 10, 20, 36, and 48 h. At the same time, intracellular TGF-beta,
      Smad2/3, Smad4 of four groups were detected by Western blot at the time point of
      10 h. RESULTS: In aspect of apoptosis, groups B-D have higher apoptosis rate than
      group A, group D has more apoptosis cells than group B and C. This was verified
      that the model was successful. Moreover, we found that group C has higher delayed
      apoptosis rate than group A, and group D has higher early apoptosis rate than
      other groups (P<0.05); compared with group A, C, D, group B has less TGF-beta
      (P<0.05). Group C secrets more TGF-beta than that in group A (P<0.05) and group D
      secrets more TGF-beta than that in group C at the time points of 20, 36, 48 h
      (P<0.05); Group C and D expressed more Smad2, Smad3 and Smad4 than group A and B
      at the time point of 10 h after treatment. Meanwhile, cells in group D expressed
      more Smads than group C. CONCLUSION: Cryoablation could promote TGF-beta and its
      pathway, and the more close to the center of the ice ball, this effect is more
      apparent.

PMID- 25952507
TI  - Silver nanoparticles at sublethal concentrations disrupt cytoskeleton and neurite
      dynamics in cultured adult neural stem cells.
AB  - Silver nanoparticles (AgNPs) have potent antimicrobial properties at
      concentrations far below those that cause cytotoxic and genotoxic effects in
      eukaryotic cells. This property has resulted in the widespread use of AgNPs in
      consumer products, leading to environmental exposures at sub-lethal levels
      through ingestion and inhalation. Although the toxicity of AgNPs has been well
      characterized, effects of environmentally relevant exposures have not been
      extensively investigated in spite of studies that suggest accumulation of silver
      in tissues, including brain. To assess the sublethal effects of AgNPs on neural
      cell function, we used cultured SVZ-NSCs, a model of neurogenesis and neural
      cells. Throughout life, neural stem cells (NSCs) in the subventricular zone (SVZ)
      of the lateral ventricles proliferate and migrate via the rostral migratory
      stream to the olfactory bulb. Once there, they complete differentiation into
      neurons and glia and integrate into existing circuits. This process of
      neurogenesis is tightly regulated, and is considered a part of healthy brain
      function. We found that 1.0 MUg/mL AgNP exposure in cultured differentiating NSCs
      induced the formation of f-actin inclusions, indicating a disruption of actin
      function. These inclusions did not co-localize with AgNPs, and therefore do not
      represent sequestered nanoparticles. Further, AgNP exposure led to a reduction in
      neurite extension and branching in live cells, cytoskeleton-mediated processes
      vital to neurogenesis. We conclude that AgNPs at sublethal concentrations disrupt
      actin dynamics in SVZ-NSCs, and that an associated disruption in neurogenesis may
      contribute to documented deficits in brain function following AgNP exposure.

PMID- 25952506
TI  - Country-level and individual correlates of overweight and obesity among primary
      school children: a cross-sectional study in seven European countries.
AB  - BACKGROUND: The present study aims to estimate childhood overweight and obesity
      prevalence and their association with individual and population-level correlates
      in Eastern and Western European countries. METHODS: Data were obtained from the
      School Children Mental Health in Europe, a cross-sectional survey conducted in
      2010 in Italy, Germany, the Netherlands, Romania, Bulgaria, Lithuania and Turkey.
      The sample consists of 5,206 school children aged 6 to 11 years old. Information
      on socio-demographics, children's height and weight, life-style and parental
      attitude were reported by the mothers. Country-level indicators were obtained
      through several data banks. Overweight and obesity in children were calculated
      according to the international age and gender-specific child Body Mass Index cut
      off points. Multivariable logistic regression models included socio-demographic,
      lifestyle, mothers' attitude, and country-level indicators to examine the
      correlates of overweight. RESULTS: Overall prevalence was 15.6% (95% CI = 19.3
      21.7%) for overweight and 4.9% (95% CI = 4.3-5.6%) for obesity. In overweight
      (including obesity), Romanian children had the highest prevalence (31.4%, 95% CI
      = 28.1-34.6%) and Italian the lowest (10.4%, 95% CI = 8.1-12.6%). Models in the
      pooled sample showed that being younger (aOR = 0.93, 95% = CI 0.87-0.97), male
      (aOR = 1.24, 95% CI = 1.07-1.43), an only child (aOR = 1.40, 95% CI = 1.07-1.84),
      spending more hours per week watching TV (aOR = 1.01, 95% CI =1.002-1.03), and
      living in an Eastern Country were associated with greater risk of childhood
      overweight (including obesity). The same predictors were significantly associated
      with childhood overweight in the model conducted in the Eastern region, but not
      in the West. Higher Gross Domestic Product and Real Domestic Product, greater
      number of motor and passenger vehicles, higher percentage of energy available
      from fat, and more public sector expenditure on health were also associated with
      lower risk for childhood overweight after adjusting for covariables in the pooled
      sample and in the east of Europe, but not in the West. CONCLUSIONS: Prevalence
      rates of overweight and obesity in school children is still high, especially in
      Eastern regions, with some socio-demographic factors and life-styles associated
      with being overweight. It is also in the Eastern region itself where better macro
      economic indicators are related with lower rates of childhood overweight. This
      represents a public health concern that deserves special attention in those
      countries undertaking economic and political transitions.

PMID- 25952508
TI  - Mechanism of the effect of glycosyltransferase GLT8D2 on fatty liver.
AB  - BACKGROUND: Recent studies have shown that some glycosyltransferases are involved
      in the development of nonalcoholic fatty liver disease (NAFLD). The objective of
      this study was to explore the effect and mechanism of glycosyltransferase GLT8D2
      on fatty liver. METHODS: Rat model of NAFLD was established by induction with
      high-fat-diet. The GLT8D2 expression in rat liver was examined using
      immunohistochemistry. Oil Red O staining and triglyceride assay were used to
      measure the effect of abnormal GLT8D2 expression on lipid accumulation in HepG2
      cells. The expression levels of lipid metabolism-related key molecules, namely
      sterol regulatory element-binding protein-1c (SREBP-1c), stearoyl-coA desaturase
      (SCD), carnitine palmitoyltransferase-1 (CPT1) and microsomal triglyceride
      transfer protein (MTP), in HepG2 cells with abnormal GLT8D2 expression were
      determined by western blot analyses. RESULTS: The expression of GLT8D2 was higher
      in the liver of rats with NAFLD than in the control rats, and GLT8D2 was mainly
      located around lipid droplets in hepatocytes. GLT8D2 expression increased in
      steatosis HepG2 cells compared with that in normal HepG2 cells. GLT8D2 positively
      regulated lipid droplet accumulation and triglyceride content in HepG2 cells.
      Upregulation or knockdown of GLT8D2 had no effect on the expressions of SREBP-1c,
      SCD or CPT-1 proteins in HepG2 cells. However, GLT8D2 expression negatively
      regulated the expression of MTP protein in HepG2 cells. CONCLUSION: GLT8D2
      participated in NAFLD pathogenesis possibly by negatively regulating MTP
      expression. Specific inhibition of GLT8D2 via an antagonistic strategy could
      provide a potential candidate approach for treatment of NAFLD.

PMID- 25952509
TI  - Can human eyes prevent perceptual narrowing for monkey faces in human infants?
AB  - Perceptual narrowing has been observed in human infants for monkey faces: 6-month
      olds can discriminate between them, whereas older infants from 9 months of age
      display difficulty discriminating between them. The difficulty infants from 9
      months have processing monkey faces has not been clearly identified. It could be
      due to the structural characteristics of monkey faces, particularly the key
      facial features that differ from human faces. The current study aimed to
      investigate whether the information conveyed by the eyes is of importance. We
      examined whether the presence of Caucasian human eyes in monkey faces allows
      recognition to be maintained in 6-month-olds and facilitates recognition in 9-
      and 12-month-olds. Our results revealed that the presence of human eyes in monkey
      faces maintains recognition for those faces at 6 months of age and partially
      facilitates recognition of those faces at 9 months of age, but not at 12 months
      of age. The findings are interpreted in the context of perceptual narrowing and
      suggest that the attenuation of processing of other-species faces is not reversed
      by the presence of human eyes.

PMID- 25952511
TI  - Activation time analysis and electromyographic fatigue in patients with
      temporomandibular disorders during clenching.
AB  - INTRODUCTION: The use of surface electromyography (SEMG) is controversial in the
      diagnosis and subsequent treatment of temporomandibular disorders (TMD), although
      there is some evidence that the pattern of the masticatory muscles in TMD
      patients differs from controls. The aim of this study was to compare relative
      time of mandibular elevator muscle activation at different levels of activity and
      median frequency (MF) during sustained clenching. METHODS: Twenty-two women, aged
      between 18 and 48years, volunteered to participate in the study. The TMD group
      had 14 participants diagnosed as group Ia muscle disorders (RDC/TMD). The control
      group had eight healthy individuals. SEMG records were obtained from masseter and
      temporal muscles during 10s of sustained clenching. Normalized SEMG amplitudes
      were classified as minimal, moderate and maximal and time of activation in each
      level of activity was calculated and compared using two-way ANOVA (groups versus
      time). A slope of the linear regression line that fits MF values over time was
      calculated as a fatigue index for elevator muscles. RESULTS: Only the temporal
      muscles of the TMD group showed longer activation time at moderate and minimal
      activity levels compared to controls. Fatigue indexes were greater for the TMD
      group compared to controls. CONCLUSION: Results showed motor control strategies
      during sustained clenching that differentiate controls from TMD patients.

PMID- 25952512
TI  - MR Imaging of Mediastinal Masses.
AB  - The high soft tissue contrast of MR imaging enables superior tissue
      characterization of mediastinal masses, adding diagnostic specificity and often
      changing and benefiting clinical management. MR imaging can better discern cystic
      from solid content and can detect microscopic fat, hemorrhage, and fibrous
      content within lesions. In many cases, mediastinal MR imaging may prevent
      unnecessary diagnostic intervention. In other cases, MR imaging may indicate the
      optimal site for biopsy or the correct compartment for resection. Awareness of
      the efficacy of MR imaging with regard to mediastinal mass characterization and
      judicious MR imaging utilization should further improve patient care. 

PMID- 25952510
TI  - Affinity of Smectite and Divalent Metal Ions (Mg(2+), Ca(2+), Cu(2+)) with L
      leucine: An Experimental and Theoretical Approach Relevant to Astrobiology.
AB  - Earth is the only known planet bestowed with life. Several attempts have been
      made to explore the pathways of the origin of life on planet Earth. The search
      for the chemistry which gave rise to life has given answers related to the
      formation of biomonomers, and their adsorption on solid surfaces has gained much
      attention for the catalysis and stabilization processes related to the abiotic
      chemical evolution of the complex molecules of life. In this communication,
      surface interactions of L-leucine (Leu) on smectite (SMT) group of clay (viz.
      bentonite and montmorillonite) and their divalent metal ion (Mg(2+), Ca(2+) and
      Cu(2+)) incorporated on SMT has been studied to find the optimal conditions of
      time, pH, and concentration at ambient temperature (298 K). The progress of
      adsorption was followed spectrophotometrically and further characterized by FTIR,
      SEM/EDS and XRD. Leu, a neutral/non polar amino acid, was found to have more
      affinity in its zwitterionic form towards Cu(2+)- exchanged SMT and minimal
      affinity for Mg(2+)- exchanged SMT. The vibrational frequency shifts of -NH3 (+)
      and -COO(-) favor Van der Waal's forces during the course of surface interaction.
      Quantum calculations using density functional theory (DFT) have been applied to
      investigate the absolute value of metal ion affinities of Leu (Leu-M(2+) complex,
      M = Mg(2+), Ca(2+), Cu(2+)) with the help of their physico-chemical parameters.
      The hydration effect on the relative stability and geometry of the individual
      species of Leu-M(2+) * (H2O)n, (n =2 and 4) has also been evaluated within the
      supermolecule approach. Evidence gathered from investigations of surface
      interactions, divalent metal ions affinities and hydration effects with
      biomolecules may be important for better understanding of chemical evolution, the
      stabilization of biomolecules on solid surfaces and biomolecular-metal
      interactions. These results may have implications for understanding the origin of
      life and the preservation of biomarkers. 

PMID- 25952513
TI  - State of the Art: MR Imaging of Thymoma.
AB  - Thymoma is the most common primary malignancy of the anterior mediastinum and the
      most common thymic epithelial neoplasm, but it is a rare tumor that constitutes
      less than 1% of adult malignancies. Computed tomography (CT) is currently the
      imaging modality of choice for distinguishing thymoma from other anterior
      mediastinal masses, characterizing the primary tumor, and staging the disease.
      However, magnetic resonance imaging is also effective in evaluating and
      characterizing anterior mediastinal masses and staging thymoma in patients with
      contraindications to contrast-material-enhanced CT such as contrast allergy
      and/or renal failure. 

PMID- 25952514
TI  - Novel MR Imaging Applications for Pleural evaluation.
AB  - Computed tomography is the first-line modality for evaluation of chest diseases
      primarily because of its spatial resolution. Magnetic resonance (MR) imaging is
      used as a problem-solving tool to answer key questions that are vital to optimal
      patient management. MR has the potential to provide qualitative, quantitative,
      anatomic, and functional information without the use of ionizing radiation or
      nephrotoxic contrast administration. With new advances in proton MR techniques,
      MR imaging can overcome some of the inherent problems associated with imaging the
      lung. This article describes novel MR applications for evaluation of the pleura
      and pleural diseases. 

PMID- 25952515
TI  - MR Imaging of Chest Wall Tumors.
AB  - Tumors of the chest wall are uncommon lesions that represent approximately 5% of
      all thoracic malignancies. These tumors comprise a heterogeneous group of
      neoplasms that may arise from osseous structures or soft tissues and may be
      malignant or benign. Most chest wall neoplasms are malignant and include lesions
      that secondarily involve the chest wall via direct invasion or metastasis from
      intrathoracic tumors or arise as primary tumors. More than 20% of lesions may be
      detected on chest radiography. This review focuses on key features of malignant
      and benign chest wall tumors (primary and secondary) on MR imaging examinations. 

PMID- 25952516
TI  - Hyperpolarized Gas MR Imaging: Technique and Applications.
AB  - Functional imaging offers information more sensitive to changes in lung structure
      and function. Hyperpolarized helium ((3)He) and xenon ((129)Xe) MR imaging of the
      lungs provides sensitive contrast mechanisms to probe changes in pulmonary
      ventilation, microstructure, and gas exchange. Gas imaging has shifted to the use
      of (129)Xe. Xenon is well-tolerated. (129)Xe is soluble in pulmonary tissue,
      which allows exploring specific lung function characteristics involved in gas
      exchange and alveolar oxygenation. Hyperpolarized gases and (129)Xe in particular
      stand to be an excellent probe of pulmonary structure and function, and provide
      sensitive and noninvasive biomarkers for pulmonary diseases. 

PMID- 25952517
TI  - Lung Cancer Assessment Using MR Imaging: An Update.
AB  - MR imaging has emerged as a major new research and diagnostic tool for various
      pulmonary diseases, especially lung cancer. State-of-the art thoracic MR imaging
      now has the potential to be used as a substitute for traditional imaging
      techniques and/or to play a complementary role in patient management. This
      article focuses on these recent advances in MR imaging for lung cancer imaging,
      especially for pulmonary nodule assessment, lung cancer staging, postoperative
      lung function prediction, and prediction and evaluation of therapeutic response
      and recurrence. The potential and limitations of routine clinical application of
      these advances are discussed and compared with those of other modalities. 

PMID- 25952518
TI  - PET/MR Imaging for Chest Diseases: Review of Initial Studies on Pulmonary Nodules
      and Lung Cancers.
AB  - PET/MR imaging, a new hybrid modality, is thought to have great potential in
      oncologic imaging because it provides advantages of both PET, which allows
      functional imaging capability, and MR imaging, which allows high spatial
      resolution imaging without radiation exposure. Despite the inherent weakness of
      MR imaging in lung imaging, initial studies on lung cancer revealed that PET/MR
      imaging showed highly correlated standardized uptake values of lesions and
      equivalent performance in terms of lesion detection and staging compared with
      PET/computed tomography (CT). Thus, to affirm the actual clinical benefits of
      dedicated PET/MR imaging over PET/CT, prospective studies with more patients are
      warranted. 

PMID- 25952519
TI  - Imaging pulmonary arterial thromboembolism: challenges and opportunities.
AB  - Magnetic resonance (MR) angiography of the pulmonary arteries is a rapidly
      evolving technique with proven clinical usefulness. Multiple-step protocols, such
      as MR perfusion followed by high-spatial resolution MR angiography, seem to be a
      good approach for the assessment of different vascular diseases affecting the
      pulmonary arteries. In combination with other imaging sequences, MR imaging is
      one of the most comprehensive potential noninvasive imaging techniques available.

PMID- 25952520
TI  - MR Imaging of the Thoracic Aorta.
AB  - Pre- and postoperative evaluation, serial follow-up studies, and screening
      examinations of the aorta are performed with noninvasive cross-sectional imaging
      modalities like CT and MR imaging. MR imaging allows for dedicated comprehensive
      evaluation without exposure to iodinated contrast or ionizing radiation. The
      additional advantage of MR imaging is that it can provide not only morphologic
      but also functional information. The purpose of this article is to advance
      knowledge and understanding of MR imaging techniques and their application to
      common aortic pathologies. 

PMID- 25952521
TI  - MR Imaging of Thoracic Veins.
AB  - MR imaging of thoracic veins is performed to evaluate the heart and thoracic
      vasculature. The protocol can be customized to the clinical question. In the
      embryo, systemic and pulmonary vein development is closely related to heart
      development. Congenital anomalies of the thoracic veins are strongly associated
      with other cardiac and situs abnormalities. Acquired venous abnormalities are
      often iatrogenic, or secondary to malignancy. This article discusses development
      and anatomy of the thoracic venous systems, clinical MR imaging methods for their
      evaluation, and illustrates the MR imaging appearance of congenital and acquired
      abnormalities of systemic thoracic veins, coronary sinus, and pulmonary veins. 

PMID- 25952522
TI  - State-of-the-art Magnetic Resonance Imaging in Vascular Thoracic Outlet Syndrome.
AB  - Vascular thoracic outlet syndrome is caused by compression of subclavian/axillary
      vessels during their passage from the thoracic cavity to the axilla. Early
      diagnosis and treatment is important to prevent debilitating outcomes of vascular
      thoracic outlet syndrome. Contrast-enhanced three-dimensional (3D) magnetic
      resonance angiography (MRA) with equilibrium phase using provocative arm
      positioning is the optimal examination to determine presence, degree of vascular
      compression, and complications of vascular thoracic outlet syndrome. This article
      reviews thoracic outlet anatomy, disorders of the vascular component, and typical
      imaging findings by contrast-enhanced 3D MRA. 

PMID- 25952523
TI  - Pediatric Chest MR Imaging: Sedation, Techniques, and Extracardiac Vessels.
AB  - Thoracic MR imaging in the pediatric population provides unique challenges
      requiring tailored protocols and a practical approach to pediatric issues, such
      as patient motion and sedation. Concern regarding the use of ionizing radiation
      in the pediatric population has continued to advance the use of MR imaging
      despite these challenges. This article provides a practical approach to thoracic
      vascular MR imaging with special attention paid to pediatric-specific issues such
      as sedation. Thoracic vascular anatomy and pathology are discussed with an
      emphasis on protocols that can facilitate accurate diagnosis. 

PMID- 25952524
TI  - Pediatric Chest MR Imaging: Lung and Airways.
AB  - Advances in technology coupled with optimized protocols now permit evaluation of
      the lungs with magnetic resonance (MR) imaging in the pediatric population.
      Although computed tomography remains the preferred imaging modality for this
      purpose, MR imaging provides a radiation-free alternative that can answer many
      important clinical questions and provide additional data. In addition, the use of
      newer techniques and equipment such as MR-imaging-compatible spirometers allows
      for functional assessment of the pediatric airways. This article reviews the up
      to-date MR imaging techniques as well as imaging findings of selected clinically
      important disorders that affect the lungs and airways in the pediatric
      population. 

PMID- 25952526
TI  - Chest MR Imaging.

PMID- 25952527
TI  - Irisin, an exercise-induced myokine as a metabolic regulator: an updated
      narrative review.
AB  - Irisin, as a new hormone-like myokine, is discovered in the presence of exercise
      induced peroxisome proliferator-activated receptor gamma coactivator-1-alpha (PGC
      1alpha). Which substance plays an important role in energy metabolism in each
      organ in the body and the regulation of metabolic diseases such as obesity and
      diabetes. The finding of irisin can contribute to the exploration of the novel
      and effective therapeutic targets or therapeutic strategies of these metabolic
      diseases or metabolism-associated health issues. To date, little is known
      regarding the functions and regulatory mechanisms of irisin with respect to
      metabolic diseases or metabolism-associated health issues. In this narrative
      review article, we systematically introduce its structural characteristics,
      production and distribution in tissues and organs, and the regulation and
      corresponding mechanisms for metabolic diseases or metabolism-associated health
      issues of irisin. Meanwhile, its future prospects and the development of irisin
      related products for the promotion of human health have also been proposed, which
      will benefit future research and application of irisin. Copyright (c) 2015 John
      Wiley & Sons, Ltd. 

PMID- 25952528
TI  - Ultrahigh Enzyme Activity Assembled in Layered Double Hydroxides via Mg(2+)
      Allosteric Effector.
AB  - It is well-known that some metal ions could be allosteric effectors of allosteric
      enzymes to activate/inhibit the catalytic activities of enzymes. In
      nanobiocatalytic systems constructed based on the positive metal ion-induced
      allosteric effect, the incorporated enzymes will be activated and thus exhibit
      excellent catalytic performance. Herein, we present an environmentally friendly
      strategy to construct a novel allosteric effect-based beta-galactosidase/Mg-Al
      layered double hydroxide (beta-gal/Mg-Al-LDH) nanobiocatalytic system via the
      delamination-reconstruction method. The intercalated beta-gal in the LDH
      galleries changes its conformation significantly due to the Mg(2+)-induced
      allosteric interactions and other weak interactions, which causes the activation
      of enzymatic activity. The beta-gal/Mg-Al-LDH nanobiocatalytic system shows much
      higher catalytic activity and affinity toward its substrate and about 30 times
      higher catalytic reaction velocity than the free beta-gal, which suggests that
      Mg(2+)-induced allosteric effect plays a vital role in the improvement of
      enzymatic performance. 

PMID- 25952530
TI  - Norwegian General Motor Function assessment as an outcome measure for a frail
      elderly population: A validity study.
AB  - AIM: To establish the validity of the Norwegian General Motor Function (NGMF)
      assessment scale. METHOD: To establish construct and criteria validity,
      Spearman's rank correlation coefficients were calculated for the NGMF, and age,
      sex, medical conditions, history of falls and to four functional tests. Content
      validity was evaluated by asking participating physiotherapists about the
      usefulness of the items in the scale. Absolute reliability was evaluated by
      establishing the standard error of measurement and the minimal detectable change
      at the 95% level of confidence for total scores of the NGMF subscales for
      dependence, pain and insecurity. RESULTS: Construct validity was established to
      medical status and medication with subscales dependence and insecurity but not to
      subscale pain. Criterion validity was established between the NGMF subscales
      dependence, pain and insecurity, and the Barthel Index, the Falls Efficacy Scale
      to subscales dependence and insecurity, but not with pain, and the Timed Up-and
      Go test, to subscale insecurity. Neither the Chair Stand Test nor registered
      falls were significantly associated with any of the subscales of the NGMF.
      Content validity of the NGMF was perceived relevant to work in a geriatric
      setting and as a communication tool for a multidisciplinary team. Minimal
      detectable change was calculated for dependence (2.76), pain (4.9) and insecurity
      (6.1), respectively. CONCLUSION: The construct, criteria and content validity of
      the NGMF was established.

PMID- 25952529
TI  - AECHL-1, a novel triterpenoid, targets tumor neo-vasculature and impairs the
      endothelial cell cytoskeleton.
AB  - Tumor angiogenesis is characterized by abnormal vessel morphology leading to
      erratic and insufficient delivery of chemotherapeutics and oxygen, making the
      tumor core not only highly hypoxic but also unresponsive toward treatment. Such
      hypoxic conditions promote tumor aggressiveness, leading to the establishment of
      metastatic disease. Most anti-angiogenic treatments aim toward the destruction of
      tumor vasculature, which proves countereffective by further increasing its
      aggressive nature. Hence, developing drugs which target or regulate these
      processes might lead to a better delivery of chemotherapeutics resulting in tumor
      shrinkage. Plant-derived natural compounds having a bioactive ingredient,
      especially triterpenoids, have been known to possess anticancer properties. AECHL
      1, a recently isolated novel triterpenoid with proven anticancer potential, is
      seemingly noncytotoxic toward HEK 293 and HUVECs. Also, cytotoxicity was absent
      during in vivo studies involving intraperitoneal injections with 5 ug/kg body
      weight AECHL-1 on SCID mice. When used at subtoxic doses, it was found to be
      effective in suppression of neo-vessel formation as demonstrated in the chick
      chorioallantoic membrane, rat aortic rings, Matrigel plugs and xenograft tumors
      implanted in SCID mice. Tumor vasculature from AECHL-1-treated mice showed
      greater mural cell coverage and relatively normalized architecture.
      Investigations into the molecular mechanisms responsible for these observations
      revealed an effect on the actin cytoskeleton of stimulated HUVECs as well as the
      VEGFR2-mediated MAPK pathway. AECHL-1 could effectively distinguish between
      stimulated and nonstimulated endothelial cells. AECHL-1 could also downregulate
      HIF-1alpha expression and VEGF secretion under hypoxic conditions, thus reducing
      the fears of unnecessarily aggravating tumor metastasis as a result of anti
      angiogenic therapy. Results obtained from the aforementioned studies make it
      clear that though AECHL-1 shows promise in discouraging and pruning neo
      vasculature, it may not affect existing vasculature as the doses used for the
      assays are significantly lower than the ones causing endothelial cell death and
      has potential to be considered as a candidate for therapeutic drug development.

PMID- 25952531
TI  - Comparative Analysis of Left- Versus Right-sided Resection in Klatskin Tumor
      Surgery: can Lesion Side be Considered a Prognostic Factor?
AB  - BACKGROUND: Achievement of negative margins is the goal of curative intent
      surgery for hilar cholangiocarcinoma. This study analyzed factors affecting
      survival in hilar cholangiocarcinoma patients and compared short- and long-term
      outcomes of left- and right-sided resections. METHODS: One hundred and five
      patients out of 124 diagnosed with Klatskin tumors underwent major liver
      resection. Sixty-one patients underwent right-sided resections (right group),
      whereas 44 underwent left-sided resections (left group). Perioperative morbidity,
      perioperative mortality, and overall and disease-free survival were compared
      between the groups. RESULTS: Morbidity and mortality were higher in the right
      group (59 and 8.2%, respectively) than in the left group (38.6 and 2.3%,
      respectively) (p < 0.005). The most frequent cause of death was liver failure.
      The R0 rate was 75.4% in the right and 61.4% in the left group. The 5-year
      survival rate was 42.8% in the right and 35.3% in the left group (p < 0.05).
      Patients in the left group more frequently developed local recurrence (87 vs. 69%
      in the right group). CONCLUSION: Lesion side impacts outcome: right resections
      still cause significant morbidity related to extensive parenchymal sacrifice but
      are associated with better long-term survival because right hepatic pedicle
      resection enables better radicality compared with left resections.

PMID- 25952533
TI  - Lenalidomide for mantle cell lymphoma.
AB  - Mantle cell lymphoma accounts for 6% of all non-Hodgkin lymphomas. It is a
      biologically and clinically heterogeneous disease and treatment may be difficult,
      since most patients present at an older age, being unable to undergo intensive
      chemotherapy. Lenalidomide is an approved medication for relapsed mantle cell
      lymphoma in patients who received at least two lines of therapy, including
      bortezomib. New insights into the mechanisms of action of lenalidomide provided
      ground for novel combinations that may be more tolerable, while still efficient,
      for this patient population. In this review, we evaluate the current paradigm for
      lenalidomide in mantle cell lymphoma. 

PMID- 25952532
TI  - Basal-prandial versus premixed insulin in patients with type 2 diabetes requiring
      insulin intensification after basal insulin optimization: A 24-week randomized
      non-inferiority trial.
AB  - BACKGROUND: The aim of the present 24-week multicentre randomized non-inferiority
      trial was to compare the efficacy and safety of two insulin intensification
      strategies in uncontrolled type 2 diabetes despite optimized basal insulin
      therapy. METHODS: Patients with fasting plasma glucose (FPG) <130 mg/dL and HbA1c
      7.0%-10.0% while on insulin glargine were randomized to a basal-prandial group
      (stepwise addition of insulin glulisine) or a premixed insulin group (insulin
      aspart/insulin aspart protamine 30/70 starting with 6 IU twice daily). The
      primary endpoint was the change in HbA1c after 24 weeks (non-inferiority margin
      0.4%). RESULTS: At Week 24, the adjusted mean change from baseline HbA1c was 
      0.94 +/- 0.09% and -1.04 +/- 0.09% in basal-prandial and premixed insulin groups,
      respectively, with a mean difference of -0.09% (95% confidence interval [CI] 
      0.35, 0.16). A lower rate of hypoglycemia with a similar reduction in HbA1c was
      observed during stabilization of the total daily insulin dose in the premixed
      insulin group (Weeks 0-12). After stabilization of the total daily insulin dose,
      the rate of hypoglycemia and the total daily insulin dose were similar in the two
      groups. CONCLUSIONS: The efficacy and safety of the two intensifying regimens
      were similar after stabilization of the total daily insulin dose when oral agents
      were maintained. Starting with a lower total daily insulin dose with a gradual
      change in the treatment regimen was helpful in reducing the rate of hypoglycemia
      during initial stabilization of the total daily insulin dose.

PMID- 25952534
TI  - Composites of electrospun-fibers and hydrogels: A potential solution to current
      challenges in biological and biomedical field.
AB  - With increasingly rigorous requirements for biomaterials, the design and
      fabrication of novel materials with smart functions are urgently needed. The
      fabrication of composite materials that can surmount individual shortcomings as
      well as bring synergistic benefits represents an efficient route to improve the
      performances and expand application scopes of biomaterials. Due to their unique
      structures and properties, electrospun-fibers and hydrogels have been widely
      applied in many biological and biomedical fields. Based on this, more and more
      attentions have been paid on the composites of electrospun-fibers and hydrogels
      as biomaterials, aiming to bring their individual superiority into full play as
      well as remedy their intrinsic defects. This review summarizes approaches used to
      integrate electrospun-fibers and hydrogels into various structures and the
      development of their composites as a potential solution to some current
      challenges in drug delivery, tissue engineering and some other bio-related
      aspects. The individual roles and mutual synergy of electrospun-fibers and
      hydrogels in the composites will be emphasized.

PMID- 25952535
TI  - Plant scientists celebrate new woody plant genome.

PMID- 25952536
TI  - The limits to leaf and root plasticity: what is so special about specific root
      length?

PMID- 25952537
TI  - Beyond the heterostylous syndrome.

PMID- 25952538
TI  - A genetic route to yellow flowers.

PMID- 25952539
TI  - Direct observation of finite size effects in chains of antiferromagnetically
      coupled spins.
AB  - Finite spin chains made of few magnetic ions are the ultimate-size structures
      that can be engineered to perform spin manipulations for quantum information
      devices. Their spin structure is expected to show finite size effects and its
      knowledge is of great importance both for fundamental physics and applications.
      Until now a direct and quantitative measurement of the spatial distribution of
      the magnetization of such small structures has not been achieved even with the
      most advanced microscopic techniques. Here we present measurements of the spin
      density distribution of a finite chain of eight spin-3/2 ions using polarized
      neutron diffraction. The data reveal edge effects that are a consequence of the
      finite size and of the parity of the chain and indicate a noncollinear spin
      arrangement. This is in contrast with the uniform spin distribution observed in
      the parent closed chain and the collinear arrangement in odd-open chains. 

PMID- 25952540
TI  - Altered viscerotopic cortical innervation in patients with irritable bowel
      syndrome.
AB  - BACKGROUND: Studies have demonstrated the existence of regional gray matter and
      white matter (WM) alterations in the brains of patients with irritable bowel
      syndrome (IBS), but the extent to which altered anatomical connectivity between
      brain regions is altered in IBS remains incompletely understood. METHODS: In this
      study, magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) were
      used to identify significant brain connectivity differences between IBS patients
      and healthy control (HC) subjects. Based on MRI and DTI volumes acquired from 66
      IBS patients and 23 HC subjects, multivariate regression was used to investigate
      whether subject age, sex, cortical thickness, or the mean fractional anisotropy
      (FA) of WM connections innervating each location on the cortex could predict IBS
      diagnosis. KEY RESULTS: HC and IBS subjects were found to differ significantly
      within both left and right viscerotopic portions of the primary somatosensory
      cortex (S1), with the mean FA of WM bundles innervating S1 being the predictor
      variable responsible for these significant differences. CONCLUSIONS & INFERENCES:
      These preliminary findings illustrate how a chronic visceral pain syndrome and
      brain structure are related in the cohort examined, and because of their
      indication that IBS diagnosis is associated with anatomic neuropathology of
      potential neurological relevance in this patient sample.

PMID- 25952541
TI  - Tea Polyphenols Protect Against Methylmercury-Induced Cell Injury in Rat Primary
      Cultured Astrocytes, Involvement of Oxidative Stress and Glutamate
      Uptake/Metabolism Disorders.
AB  - Methylmercury (MeHg) is an extremely dangerous environmental contaminant,
      accumulating preferentially in CNS and causing a series of cytotoxic effects.
      However, the precise mechanisms are still incompletely understood. The current
      study explored the mechanisms that contribute to MeHg-induced cell injury
      focusing on the oxidative stress and Glu uptake/metabolism disorders in rat
      primary cultured astrocytes. Moreover, the neuroprotective effects of tea
      polyphenols (TP), a natural antioxidant, against MeHg cytotoxicity were also
      investigated. Astrocytes were exposed to 0, 2.5, 5, 10, and 20 MUM MeHgCl for 6
      30 h, or pretreated with 50, 100, 200, and 400 MUM TP for 1-12 h; cell viability
      and LDH release were then determined. For further experiments, 50, 100, and 200
      MUM of TP pretreatment for 6 h followed by 10 MUM MeHgCl for 24 h were performed
      for the examination of the responses of astrocytes, specifically addressing NPSH
      levels, ROS generation, ATPase activity, the expressions of Nrf2 pathway as well
      as Glu metabolism enzyme GS and Glu transporters (GLAST and GLT-1). Exposure of
      MeHg resulted in damages of astrocytes, which were shown by a loss of cell
      viability, and supported by high levels of LDH release, morphological changes,
      apoptosis rates, and NPSH depletion. In addition, astrocytes were sensitive to
      MeHg-mediated oxidative stress, a finding that is consistent with ROS
      overproduction; Nrf2 as well as its downstream genes HO-1 and gamma-GCSh were
      markedly upregulated. Moreover, MeHg significantly inhibited GS activity, as well
      as expressions of GS, GLAST, and GLT-1. On the contrary, pretreatment with TP
      presented a concentration-dependent prevention against MeHg-mediated cytotoxic
      effects of astrocytes. In conclusion, the findings clearly indicated that MeHg
      aggravated oxidative stress and Glu uptake/metabolism dysfunction in astrocytes.
      TP possesses some abilities to prevent MeHg cytotoxicity through its
      antioxidative properties.

PMID- 25952542
TI  - Formation and Implications of Alpha-Synuclein Radical in Maneb- and Paraquat
      Induced Models of Parkinson's Disease.
AB  - Parkinson's disease (PD) is a debilitating, progressive, neurodegenerative
      disorder characterized by progressive loss of dopaminergic neurons and motor
      deficits. Alpha-synuclein-containing aggregates represent a feature of a variety
      of neurodegenerative disorders, including PD; however, the mechanism that
      initiates and promotes intraneuronal alpha-synuclein aggregation remains unknown.
      We hypothesized protein radical formation as an initiating mechanism for alpha
      synuclein aggregation. Therefore, we used the highly sensitive immuno-spin
      trapping technique to investigate protein radical formation as a possible
      mechanism of alpha-synuclein aggregation as well as to investigate the source of
      protein radical formation in the midbrains of Maneb- and paraquat-coexposed mice.
      Coexposure to Maneb and paraquat for 6 weeks resulted in active microgliosis,
      NADPH oxidase activation, and inducible nitric oxide synthase (iNOS) induction,
      which culminated in protein radical formation in the midbrains of mice. Results
      obtained with immuno-spin trapping and immunoprecipitation experiments confirmed
      formation of alpha-synuclein radicals in dopaminergic neurons of exposed mice.
      Free radical formation requires NADPH oxidase and iNOS, as indicated by decreased
      protein radical formation in knockout mice (P47phox(-/-) and iNOS(-/-)) and in
      mice treated with inhibitors such as FeTPPS (a peroxynitrite decomposition
      catalyst), 1400 W (an iNOS inhibitor), or apocynin (a NADPH oxidase inhibitor).
      Concurrence of protein radical formation with dopaminergic neuronal death
      indicated a link between protein radicals and disease progression. Taken
      together, these results show for the first time the formation and detection of
      the alpha-synuclein radical and suggest that NADPH oxidase and iNOS play roles in
      peroxynitrite-mediated protein radical formation and subsequent neuronal death in
      the midbrains of Maneb- and paraquat-coexposed mice.

PMID- 25952543
TI  - Phosphorylation of Connexin 43 by Cdk5 Modulates Neuronal Migration During
      Embryonic Brain Development.
AB  - The gap junction protein, connexin 43 (Cx43), is only present and abundantly
      expressed in astrocytes but is absent in neurons in the mature brain tissues.
      However, both the expression and function of Cx43 in neurons during brain
      embryonic development remain largely unexplored. In the present study, we
      confirmed that Cx43 is expressed in the migrating neurons in the embryonic stage
      of the brain. Neuron-specific Cx43 conditional knockout (cKO) using Cre-loxP
      technique impairs neuronal migration and formation of laminar structure in
      cerebral cortex during brain embryonic development. The animal behavior tests
      demonstrated that, at the adult stage, neuronal Cx43 cKO mice exhibit normal
      learning and memory functions but increased anxiety-like behavior. We also found
      that during the embryonic development, the gradually decreased Cx43 expression in
      the cortex is closely correlated with the upregulation of cyclin-dependent kinase
      5 (Cdk5) activity. Cdk5 directly phosphorylates Cx43 at Ser279 and Ser282, which,
      in consequence, inhibits the membrane targeting of Cx43 and promotes its
      proteasome-dependent degradation. In summary, our findings revealed that the
      embryonic expression of Cx43 in neurons regulates processes of neuronal migration
      and positioning in the developing brain by controlling astrocyte-neuron
      interactions during brain embryonic development, and Cdk5 directly phosphorylates
      Cx43, which regulates the membrane localization and degradation of Cx43 in
      neurons.

PMID- 25952545
TI  - Optimal footfall patterns for cost minimization in running.
AB  - Optimality in footfall pattern use is often studied in relation to running
      performance and injury risk. The typical variables assessed (metabolic cost,
      impact force) represent only two of many potential variables runners might want
      to minimize situationally. Here we used optimal control theory to predict optimal
      model-based running mechanics with 44 different cost functions. We tallied the
      frequency of different footfall patterns, then examined which patterns minimized
      which types of cost functions. When the model wore shoes, rearfoot striking (RFS)
      was predicted by 57% of the cost functions and was consistently optimal for
      functions related to whole-body energy expenditure and peak joint contact forces.
      No other footfall pattern was predicted by more than 25% of the functions. Non
      RFS patterns tended to be optimal for functions that gave equal weight to all
      muscles, avoiding localized muscle fatigue. Non-RFS patterns were also predicted
      when minimizing average joint contact forces. Similar predictions were seen when
      the model ran barefoot, where RFS was optimal for 55% of the functions. The
      results suggest that RFS is the most versatile footfall pattern (optimal for the
      greatest number of goals), and may explain why RFS is the most common pattern in
      recreational shod runners. We argue that natural non-RFS runners are not
      necessarily behaving "sub-optimally", but rather may be optimizing their gaits on
      factors not tested here (e.g. comfort, which is difficult to quantify). In
      addition, switching from RFS to non-RFS may reduce the joint load accumulated
      during a run if speed and step length are maintained. 

PMID- 25952544
TI  - Botanical Drug Puerarin Attenuates 6-Hydroxydopamine (6-OHDA)-Induced
      Neurotoxicity via Upregulating Mitochondrial Enzyme Arginase-2.
AB  - Inhibition of nitric oxide synthases (NOSs) shows promise to halt the progression
      of neurodegenerative diseases. The present study was designed to explore whether
      botanical isoflavone puerarin could attenuate nitric oxide (NO)-mediated
      neurotoxicity via modulating the enzymes in the L-arginine-NO pathway. Neurotoxin
      6-hydroxydopamine (6-OHDA) is well known to induce neurodegeneration via a NO
      dependent mechanism. We first validated that puerarin protected rat dopamingeric
      PC12 cells against 6-OHDA-induced neurotoxicity in a concentration-dependent
      manner. We subsequently profiled the cellular responses to puerarin by a
      proteomic response fingerprinting approach. A total of 16 protein spots with >1.5
      fold change of intensity were selected and identified by mass spectrometry. As
      one of puerarin-upregulated proteins, mitochondrial arginase-2 hydrolyzes L
      arginine to L-ornithine, thereby competing with neuronal NOS for substrate L
      arginine in mitochondria. Thus, we hypothesize that puerain may attenuate nitric
      oxide (NO)-mediated mitochondrial injury via increasing arginase-2 expression.
      Western blot and reverse transcription polymerase chain reaction (RT-PCR)
      analyses confirmed that puerarin increased arginase-2 expression in a
      concentration- and time-dependent manner. Accordingly, puerarin suppressed 6-OHDA
      induced NO production and neurotoxicity in PC12 cells and primary rat midbrain
      neurons. Arginase inhibitor BEC diminished the effect of puerarin on 6-OHDA
      induced NO production and neurotoxicity. The activation of arginase-2 by puerarin
      represents an endogenous mechanism for specific control of NO-mediated
      mitochondrial damage. Thus, puerarin is a useful lead for suppressing NO-mediated
      neurotoxicity in neurodegenerative diseases. Graphical Abstract Arginase-2
      dependent mechanism underlying the neuroprotective activity of puerarin. 

PMID- 25952546
TI  - Practical approach to subject-specific estimation of knee joint contact force.
AB  - Compressive forces experienced at the knee can significantly contribute to
      cartilage degeneration. Musculoskeletal models enable predictions of the internal
      forces experienced at the knee, but validation is often not possible, as
      experimental data detailing loading at the knee joint is limited. Recently
      available data reporting compressive knee force through direct measurement using
      instrumented total knee replacements offer a unique opportunity to evaluate the
      accuracy of models. Previous studies have highlighted the importance of subject
      specificity in increasing the accuracy of model predictions; however, these
      techniques may be unrealistic outside of a research setting. Therefore, the goal
      of our work was to identify a practical approach for accurate prediction of
      tibiofemoral knee contact force (KCF). Four methods for prediction of knee
      contact force were compared: (1) standard static optimization, (2) uniform muscle
      coordination weighting, (3) subject-specific muscle coordination weighting and
      (4) subject-specific strength adjustments. Walking trials for three subjects with
      instrumented knee replacements were used to evaluate the accuracy of model
      predictions. Predictions utilizing subject-specific muscle coordination weighting
      yielded the best agreement with experimental data; however this method required
      in vivo data for weighting factor calibration. Including subject-specific
      strength adjustments improved models' predictions compared to standard static
      optimization, with errors in peak KCF less than 0.5 body weight for all subjects.
      Overall, combining clinical assessments of muscle strength with standard tools
      available in the OpenSim software package, such as inverse kinematics and static
      optimization, appears to be a practical method for predicting joint contact force
      that can be implemented for many applications. 

PMID- 25952547
TI  - The Effects of a Hatha Yoga Intervention on Facets of Distress Tolerance.
AB  - Individuals with low distress tolerance (DT) experience negative emotion as
      particularly threatening and are highly motivated to reduce or avoid such
      affective experiences. Consequently, these individuals have difficulty regulating
      emotions and tend to engage in maladaptive strategies, such as overeating, as a
      means to reduce or avoid distress. Hatha yoga encourages one to implement present
      centered awareness and non-reaction in the face of physical and psychological
      discomfort and, thus, emerges as a potential strategy for increasing DT. To test
      whether a hatha yoga intervention can enhance DT, a transdiagnostic risk and
      maintenance factor, this study randomly assigned females high in emotional eating
      in response to stress (N = 52) either to an 8-week, twice-weekly hatha (Bikram)
      yoga intervention or to a waitlist control condition. Self-reported DT and
      emotional eating were measured at baseline, weekly during treatment, and 1-week
      post-treatment. Consistent with prediction, participants in the yoga condition
      reported greater increases in DT over the course of the intervention relative to
      waitlist participants (Cohen's d = .82). Also consistent with prediction, the
      reduction in emotional eating was greater for the yoga condition than the
      waitlist condition (Cohen's d = .92). Importantly, reductions distress
      absorption, a specific sub-facet of DT, accounted for 15% of the variance in
      emotional eating, a hallmark behavior of eating pathology and risk factor for
      obesity.

PMID- 25952548
TI  - The BCL-2 protein family, BH3-mimetics and cancer therapy.
AB  - Escape from apoptosis is a key attribute of tumour cells and facilitates chemo
      resistance. The 'BCL-2-regulated' or 'intrinsic' apoptotic pathway integrates
      stress and survival signalling to govern whether a cancer cell will live or die.
      Indeed, many pro-apoptotic members of the BCL-2 family have demonstrated tumour
      suppression activity in mouse models of cancer and are lost or repressed in
      certain human cancers. Conversely, overexpression of pro-survival BCL-2 family
      members promotes tumorigenesis in humans and in mouse models. Many of the drugs
      currently used in the clinic mediate their therapeutic effects (at least in part)
      through the activation of the BCL-2-regulated apoptotic pathway. However,
      initiators of this apoptotic pathway, such as p53, are mutated, lost or silenced
      in many human cancers rendering them refractory to treatment. To counter such
      resistance mechanisms, a novel class of therapeutics, 'BH3-mimetics', has been
      developed. These drugs directly activate apoptosis by binding and inhibiting
      select antiapoptotic BCL-2 family members and thereby bypass the requirement for
      upstream initiators, such as p53. In this review, we discuss the role of the BCL
      2 protein family in the development and treatment of cancer, with an emphasis on
      mechanistic studies using well-established mouse models of cancer, before
      describing the development and already recognised potential of the BH3-mimetic
      compounds. 

PMID- 25952549
TI  - RCAD/Ufl1, a Ufm1 E3 ligase, is essential for hematopoietic stem cell function
      and murine hematopoiesis.
AB  - The Ufm1 conjugation system is a novel ubiquitin-like modification system,
      consisting of Ufm1, Uba5 (E1), Ufc1 (E2) and poorly characterized E3 ligase(s).
      RCAD/Ufl1 (also known as KIAA0776, NLBP and Maxer) was reported to function as a
      Ufm1 E3 ligase in ufmylation (Ufm1-mediated conjugation) of DDRGK1 and ASC1
      proteins. It has also been implicated in estrogen receptor signaling, unfolded
      protein response (UPR) and neurodegeneration, yet its physiological function
      remains completely unknown. In this study, we report that RCAD/Ufl1 is essential
      for embryonic development, hematopoietic stem cell (HSC) survival and erythroid
      differentiation. Both germ-line and somatic deletion of RCAD/Ufl1 impaired
      hematopoietic development, resulting in severe anemia, cytopenia and ultimately
      animal death. Depletion of RCAD/Ufl1 caused elevated endoplasmic reticulum stress
      and evoked UPR in bone marrow cells. In addition, loss of RCAD/Ufl1 blocked
      autophagic degradation, increased mitochondrial mass and reactive oxygen species,
      and led to DNA damage response, p53 activation and enhanced cell death of HSCs.
      Collectively, our study provides the first genetic evidence for the indispensable
      role of RCAD/Ufl1 in murine hematopoiesis and development. The finding of
      RCAD/Ufl1 as a key regulator of cellular stress response sheds a light into the
      role of a novel protein network including RCAD/Ufl1 and its associated proteins
      in regulating cellular homeostasis. 

PMID- 25952550
TI  - Transcendental Meditation for the improvement of health and wellbeing in
      community-dwelling dementia caregivers [TRANSCENDENT]: a randomised wait-list
      controlled trial.
AB  - BACKGROUND: Dementia is a prevalent neurodegenerative disorder affecting an
      estimated 24.3 million people across the globe. The burden on those caring for
      people with dementia is substantial, with widespread implications for the
      caregiver, the care recipient and the community. Relaxation techniques, such as
      Transcendental Meditation(r) (TM), have been shown to reduce stress and anxiety
      in healthy workers; similar benefits are anticipated in dementia caregivers. The
      objective of this study was to ascertain whether TM can improve psychological
      stress, quality of life, affect and cognitive performance in dementia caregivers.
      METHODS: The study was conducted as a pilot prospective, multi-centre, community
      based, randomised wait-list controlled trial. Community-dwelling caregivers of
      persons with diagnosed dementia were randomly assigned to a 12-week (14-hour) TM
      training program or wait-list control. Participants were assessed for quality of
      life, stress, affect, cognitive performance and adverse effects. The feasibility
      of the study was also evaluated. RESULTS: Seventeen caregivers were recruited and
      randomised. Improvements in WebNeuro response speed scores over time were
      significantly (p = 0.03) greater in the TM group relative to control. Changes
      between groups over time in all other primary and secondary outcome measures did
      not reach statistical significance. However, there was a trend toward greater
      improvement in WebNeuro stress, depression and negativity bias scores in the TM
      group. Adverse events were reported amongst 63 % of TM-treated subjects; however,
      events were generally transient, of mild-moderate intensity and only 'possibly'
      related to TM. CONCLUSIONS: Dementia caregivers exposed to TM demonstrated
      varying degrees of improvement in several measures of cognitive function, mood,
      quality of life and stress following exposure to TM. However, as the pilot study
      was underpowered, no firm conclusions can be made about the effectiveness of TM
      in this caregiver population. Findings from full-scale trials are now warranted.
      TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry
      ACTRN12613000184774 (Registered 15th February 2013).

PMID- 25952551
TI  - Unraveling incompatibility between wheat and the fungal pathogen Zymoseptoria
      tritici through apoplastic proteomics.
AB  - BACKGROUND: Hemibiotrophic fungal pathogen Zymoseptoria tritici causes severe
      foliar disease in wheat. However, current knowledge of molecular mechanisms
      involved in plant resistance to Z. tritici and Z. tritici virulence factors is
      far from being complete. The present work investigated the proteome of leaf
      apoplastic fluid with emphasis on both host wheat and Z. tritici during the
      compatible and incompatible interactions. RESULTS: The proteomics analysis
      revealed rapid host responses to the biotrophic growth, including enhanced
      carbohydrate metabolism, apoplastic defenses and stress, and cell wall
      reinforcement, might contribute to resistance. Compatibility between the host and
      the pathogen was associated with inactivated plant apoplastic responses as well
      as fungal defenses to oxidative stress and perturbation of plant cell wall during
      the initial biotrophic stage, followed by the strong induction of plant defenses
      during the necrotrophic stage. To study the role of anti-oxidative stress in Z.
      tritici pathogenicity in depth, a YAP1 transcription factor regulating
      antioxidant expression was deleted and showed the contribution to anti-oxidative
      stress in Z. tritici, but was not required for pathogenicity. This result
      suggests the functional redundancy of antioxidants in the fungus. CONCLUSIONS:
      The data demonstrate that incompatibility is probably resulted from the proteome
      level activation of host apoplastic defenses as well as fungal incapability to
      adapt to stress and interfere with host cell at the biotrophic stage of the
      interaction.

PMID- 25952553
TI  - Systematic review, meta-analysis and economic modelling of molecular diagnostic
      tests for antibiotic resistance in tuberculosis.
AB  - BACKGROUND: Drug-resistant tuberculosis (TB), especially multidrug-resistant
      (MDR, resistance to rifampicin and isoniazid) disease, is associated with a worse
      patient outcome. Drug resistance diagnosed using microbiological culture takes
      days to weeks, as TB bacteria grow slowly. Rapid molecular tests for drug
      resistance detection (1 day) are commercially available and may promote faster
      initiation of appropriate treatment. OBJECTIVES: To (1) conduct a systematic
      review of evidence regarding diagnostic accuracy of molecular genetic tests for
      drug resistance, (2) conduct a health-economic evaluation of screening and
      diagnostic strategies, including comparison of alternative models of service
      provision and assessment of the value of targeting rapid testing at high-risk
      subgroups, and (3) construct a transmission-dynamic mathematical model that
      translates the estimates of diagnostic accuracy into estimates of clinical
      impact. REVIEW METHODS AND DATA SOURCES: A standardised search strategy
      identified relevant studies from EMBASE, PubMed, MEDLINE, Bioscience Information
      Service (BIOSIS), System for Information on Grey Literature in Europe Social
      Policy & Practice (SIGLE) and Web of Science, published between 1 January 2000
      and 15 August 2013. Additional 'grey' sources were included. Quality was assessed
      using quality assessment of diagnostic accuracy studies version 2 (QUADAS-2). For
      each diagnostic strategy and population subgroup, a care pathway was constructed
      to specify which medical treatments and health services that individuals would
      receive from presentation to the point where they either did or did not complete
      TB treatment successfully. A total cost was estimated from a health service
      perspective for each care pathway, and the health impact was estimated in terms
      of the mean discounted quality-adjusted life-years (QALYs) lost as a result of
      disease and treatment. Costs and QALYs were both discounted at 3.5% per year. An
      integrated transmission-dynamic and economic model was used to evaluate the cost
      effectiveness of introducing rapid molecular testing (in addition to culture and
      drug sensitivity testing). Probabilistic sensitivity analysis was performed to
      evaluate the impact on cost-effectiveness of diagnostic and treatment time
      delays, diagnosis and treatment costs, and associated QALYs. RESULTS: A total of
      8922 titles and abstracts were identified, with 557 papers being potentially
      eligible. Of these, 56 studies contained sufficient test information for
      analysis. All three commercial tests performed well when detecting drug
      resistance in clinical samples, although with evidence of heterogeneity between
      studies. Pooled sensitivity for GenoType(r) MTBDRplus (Hain Lifescience, Nehren,
      Germany) (isoniazid and rifampicin resistance), INNO-LiPA Rif.TB(r) (Fujirebio
      Europe, Ghent, Belgium) (rifampicin resistance) and Xpert(r) MTB/RIF (Cepheid
      Inc., Sunnyvale, CA, USA) (rifampicin resistance) was 83.4%, 94.6%, 95.4% and
      96.8%, respectively; equivalent pooled specificity was 99.6%, 98.2%, 99.7% and
      98.4%, respectively. Results of the transmission model suggest that all of the
      rapid assays considered here, if added to the current diagnostic pathway, would
      be cost-saving and achieve a reduction in expected QALY loss compared with
      current practice. GenoType MTBDRplus appeared to be the most cost-effective of
      the rapid tests in the South Asian population, although results were similar for
      GeneXpert. In all other scenarios GeneXpert appeared to be the most cost
      effective strategy. CONCLUSIONS: Rapid molecular tests for rifampicin and
      isoniazid resistance were sensitive and specific. They may also be cost-effective
      when added to culture drug susceptibility testing in the UK. There is global
      interest in point-of-care testing and further work is needed to review the
      performance of emerging tests and the wider health-economic impact of
      decentralised testing in clinics and primary care, as well as non-health-care
      settings, such as shelters and prisons. STUDY REGISTRATION: This study is
      registered as PROSPERO CRD42011001537. FUNDING: The National Institute for Health
      Research Health Technology Assessment programme.

PMID- 25952554
TI  - Biomechanical comparison of a transiliac internal fixator and two iliosacral
      screws in transforaminal sacral fractures: a finite element analysis.
AB  - PURPOSE: Vertically unstable sacral transforaminal fractures can be stabilized
      with a transiliac internal fixator (TIFI) or two iliosacral screws (IS). This
      study was designed to compare stiffness between TIFI and IS. METHODS: Using CT
      images finite element model of the pelvis was developed. Denis II type fracture
      was simulated and fixed either with TIFI or two IS. The sacral base was loaded
      vertically (250-500 N), displacement magnitudes on medial and lateral fracture
      surface and the maximum bone stress were calculated. The intact pelvis was used
      as a reference. Stiffness was determined by linear regression of load and
      displacement, computed stiffness ratio %. The von Mises stress was expressed as %
      ratio, evaluation of colour mapping was made. RESULTS: The mean stiffness ratio
      medially in TIFI was 75.22%, in IS 46.54% (p = 0.00005), laterally in TIFI
      57.88%, in IS 44.74% ( p = 0.03996). The von Mises stress ratio of TIFI was
      139.27%, of IS 565.35% ( p < 0.00001). CONCLUSIONS: Significantly higher
      stiffness and lower stress were found in TIFI model. TIFI provides a lower risk
      of over-compression of the fracture line in comparison with IS. TIFI thus
      exhibits superiority for fixation of trans- foraminal fractures, particularly
      with comminutive zone.

PMID- 25952552
TI  - Physicochemical properties of calcium silicate cements associated with
      microparticulate and nanoparticulate radiopacifiers.
AB  - OBJECTIVES: The objective of this paper was to evaluate the physicochemical
      properties of calcium silicate cements with different chemical compositions,
      associated with radiopacifying agents. MATERIALS AND METHODS: Mineral trioxide
      aggregate (MTA) Angelus, calcium silicate cement with additives (CSC), and
      resinous calcium silicate cement (CSCR) were evaluated, with the addition of the
      following radiopacifiers: microparticles (micro) or nanoparticles (nano) of
      zirconium oxide (ZrO(2)), niobium oxide (Nb(2)O(5)), bismuth oxide (Bi(2)O(3)),
      or calcium tungstate (CaWO(4)). Setting time was evaluated using Gilmore needles.
      Solubility was determined after immersion in water. The pH and calcium ion
      release were analyzed after 3, 12, and 24 h and 7, 14, and 21 days. The data
      obtained were submitted to analysis of variance and Tukey's test, at a level of
      significance of 5 %. RESULTS: CSC + CaWO(4) and CSCR + ZrO(2) micro, Nb(2)O(5)
      and CaWO(4) presented results similar to MTA, with a shorter final setting time
      than the other associations. CSC and CSCR+ ZrO(2) micro presented a higher degree
      of flow. All the cements evaluated presented low solubility. The materials
      presented alkaline pH and released calcium ions. CONCLUSIONS: ZrO(2) micro
      radiopacifier may be considered a potential substitute for Bi(2)O(3) when
      associated with CSC or CSCR. CLINICAL RELEVANCE: The proposed materials,
      especially when associated with ZrO(2), are potential materials for use as
      alternatives to MTA.

PMID- 25952555
TI  - Hemorrhagic shock after minor laparoscopic procedures.
AB  - Severe bleeding from injury to abdominal wall blood vessels during minor
      laparoscopic procedures can occur. Two cases of shock presenting several hours
      after surgery are presented.

PMID- 25952556
TI  - Designing learning spaces for interprofessional education in the anatomical
      sciences.
AB  - This article explores connections between interprofessional education (IPE)
      models and the design of learning spaces for undergraduate and graduate education
      in the anatomical sciences and other professional preparation. The authors argue
      that for IPE models to be successful and sustained they must be embodied in the
      environment in which interprofessional learning occurs. To elaborate these
      arguments, two exemplar tertiary education facilities are discussed: the Charles
      Perkins Centre at the University of Sydney for science education and research,
      and Victoria University's Interprofessional Clinic in Wyndham for undergraduate
      IPE in health care. Backed by well-conceived curriculum and pedagogical models,
      the architectures of these facilities embody the educational visions, methods,
      and practices they were designed to support. Subsequently, the article discusses
      the spatial implications of curriculum and pedagogical change in the teaching of
      the anatomical sciences and explores how architecture might further the
      development of IPE models in the field. In conclusion, it is argued that learning
      spaces should be designed and developed (socially) with the expressed intention
      of supporting collaborative IPE models in health education settings, including
      those in the anatomical sciences.

PMID- 25952558
TI  - Ablation of pulmonary veins works as well as more extensive treatment in
      persistent atrial fibrillation, study finds.

PMID- 25952557
TI  - Long term population impact of seven-valent pneumococcal conjugate vaccine with a
      "3+0" schedule-How do "2+1" and "3+1" schedules compare?
AB  - INTRODUCTION: Significant reductions in invasive pneumococcal disease (IPD)
      following 7-valent pneumococcal conjugate vaccine (7vPCV) are well documented,
      but population-level data comparing different schedules are sparse. We compared
      data from long-term stable surveillance in one Australian region (3 primary doses
      (3+0) schedule) with similar data from England and Wales (2+1 schedule) and the
      United States (3+1 schedule). METHODS: Incidence rate ratios (IRRs) for all,
      vaccine type, and non-vaccine type IPD were calculated by age-group, using
      comparable case definitions and time periods post 7vPCV introduction. RESULTS: At
      baseline, the % of IPD due to 7vPCV serotypes (VT) disease in children <5 years
      was 88% in Greater Sydney (GS), 83% in the United States (US), and 74% in England
      and Wales (E&W). IRR for VT IPD <5 years in GS was 0.05 (0.02-0.09), for >=65
      years was 0.15 (0.12-0.19) and for all ages 0.12 (0.10-0.13). In the US, IRR for
      VT IPD was lower in each age group, and for all ages the 95% CI of the IRR (0.06
      (0.05-0.07)), did not overlap with GS or E&W (0.14 (0.11-0.18)). In contrast, the
      IRR for IPD due to any serotype did not differ between sites for any age group or
      overall. CONCLUSIONS: Differences in direct and indirect reductions in VT IPD
      with a "3+0" 7vPCV schedule versus "2+1" or "3+1" were small. All 3 countries
      moved to 13vPCV by 2011; data post 13vPCV will be important to assess IPD impact
      using more similar baseline incidence and comparison periods.

PMID- 25952559
TI  - Exceptionally rapid CO release from a manganese(I) tricarbonyl complex derived
      from bis(4-chloro-phenylimino)acenaphthene upon exposure to visible light.
AB  - Two manganese(i) carbonyl complexes derived from alpha,alpha'-diimine ligands
      with extended conjugated framework namely [MnBr(CO)3(BIAN)] () and
      [MnBr(CO)3(MIAN)] (), have been synthesized and structurally characterized.
      Unlike the previously reported photoactive CO-releasing molecules (photoCORMs),
      these two complexes exhibit unusually high sensitivity toward low power (0.3-10
      mW) visible light (lambda >= 520 nm) even in the solid state and rapidly release
      carbon monoxide (CO) upon illumination. The role of the ligand frames in such
      activity has been examined with the help of theoretical calculations. Application
      of these photoCORMs in delivering high fluxes of CO to biological targets is
      anticipated. 

PMID- 25952560
TI  - Rab from the white shrimp Litopenaeus vannamei: characterization and its
      regulation upon environmental stress.
AB  - With the destruction of the ecological environment, shrimp cultivation in China
      has been seriously affected by outbreaks of infectious diseases. Rab, which
      belong to small GTPase Ras superfamily, can regulate multiple steps in eukaryotic
      vesicle trafficking including vesicle budding, vesicle tethering, and membrane
      fusion. Knowledge of Rab in shrimp is essential to understanding regulation and
      detoxification mechanisms of environmental stress. In this study, we analyzed the
      functions of Rab from the Pacific white shrimp, Litopenaeus vannamei. Full-length
      cDNA of Rab was obtained, which was 751 bp long, with open reading frame encoding
      206 amino acids. In this study, for the first time, the gene expression of Rab of
      L. vannamei was analyzed by quantitative real-time PCR after exposure to five
      kinds of environmental stresses (bacteria, pH, Cd, salinity and low temperature).
      The results demonstrate that Rab is sensitive and involved in bacteria, pH, and
      Cd stress responses and Rab is more sensitive to bacteria than other stresses.
      Therefore we infer that Rab may have relationship with the anti-stress mechanism
      induced by environment stress in shrimp and Rab could be used as critical
      biomarkers for environmental quality assessment.

PMID- 25952561
TI  - Cognitive rehabilitation in multiple sclerosis: a randomized controlled trial.
AB  - BACKGROUND: The evidence base in cognitive rehabilitation in multiple sclerosis
      (MS) is still sparse. OBJECTIVE: The aim of the study was to investigate the
      effects of cognitive rehabilitation on cognitive and executive coping,
      psychological well-being and psychological aspects of health-related quality of
      life (HRQoL) in patients with MS. METHODS: One hundred and twenty patients with
      cognitive complaints, taking part in a 4-week multidisciplinary rehabilitation,
      were randomized to an intervention group (n = 60) and a control group (n = 60).
      Both groups underwent neuropsychological assessment with subsequent feedback and
      took part in general multidisciplinary MS rehabilitation. Additionally, the
      intervention group participated in cognitive group sessions as well as individual
      sessions. The main focus was to formulate Goal Attainment Scaling goals for
      coping with cognitive challenges. For 3 months past rehabilitation, the
      intervention group received biweekly telephone follow-up, focusing on goal
      attainment. RESULTS: Executive functioning improved significantly from baseline
      to four and 7 months in both groups. Improvements in psychological well-being and
      psychological aspects of HRQoL occurred only in the intervention group.
      CONCLUSION: Multicomponent cognitive rehabilitation administered within the
      context of multidisciplinary rehabilitation can improve psychological well-being
      and psychological aspects of HRQoL.

PMID- 25952562
TI  - Diffusion Tensor Imaging Parameters in Mild Traumatic Brain Injury and Its
      Correlation with Early Neuropsychological Impairment: A Longitudinal Study.
AB  - We explored the prognostic value of diffusion tensor imaging (DTI) parameters of
      selected white matter (WM) tracts in predicting neuropsychological outcome, both
      at baseline and 6 months later, among well-characterized patients diagnosed with
      mild traumatic brain injury (mTBI). Sixty-one patients with mTBI (mean age=27.08;
      standard deviation [SD], 8.55) underwent scanning at an average of 10 h (SD,
      4.26) post-trauma along with assessment of their neuropsychological performance
      at an average of 4.35 h (SD, 7.08) upon full Glasgow Coma Scale recovery. Results
      were then compared to 19 healthy control participants (mean age=29.05; SD, 5.84),
      both in the acute stage and 6 months post-trauma. DTI and neuropsychological
      measures between acute and chronic phases were compared, and significant
      differences emerged. Specifically, chronic-phase fractional anisotropy and radial
      diffusivity values showed significant group differences in the corona radiata,
      anterior limb of internal capsule, cingulum, superior longitudinal fasciculus,
      optic radiation, and genu of corpus callosum. Findings also demonstrated
      associations between DTI indices and neuropsychological outcome across two time
      points. Our results provide new evidence for the use of DTI as an imaging
      biomarker and indicator of WM damage occurring in the context of mTBI, and they
      underscore the dynamic nature of brain injury and possible biological basis of
      chronic neurocognitive alterations. 

PMID- 25952564
TI  - Using lung ultrasound in an infant to detect bronchial intubation not previously
      identified by auscultation.

PMID- 25952565
TI  - A new role for alpha-synuclein in Parkinson's disease: Alteration of ER
      mitochondrial communication.
AB  - Familial cases of Parkinson's disease (PD) can be associated with overexpression
      or mutation of alpha-synuclein, a synaptic protein reported to be localized
      mainly in the cytosol and mitochondria. We recently showed that wild-type alpha
      synuclein is not present in mitochondria, as previously thought, but rather is
      located in mitochondrial-associated endoplasmic reticulum membranes. Remarkably,
      we also found that PD-related mutated alpha-synuclein results in its reduced
      association with mitochondria-associated membranes, coincident with a lower
      degree of apposition of endoplasmic reticulum with mitochondria and an increase
      in mitochondrial fragmentation, as compared with wild-type. This new subcellular
      localization of alpha-synuclein raises fundamental questions regarding the
      relationship of alpha-synuclein to mitochondria-associated membranes function, in
      both normal and pathological states. In this article, we attempt to relate
      aspects of PD pathogenesis to what is known about mitochondria-associated
      membranes' behavior and function. We hypothesize that early events occurring in
      dopaminergic neurons at the level of the mitochondria-associated membranes could
      cause long-term disturbances that lead to PD.

PMID- 25952563
TI  - Regulators and effectors of bone morphogenetic protein signalling in the
      cardiovascular system.
AB  - Bone morphogenetic proteins (BMPs) play key roles in the regulation of cell
      proliferation, differentiation and apoptosis in various tissues and organs,
      including the cardiovascular system. BMPs signal through both Smad-dependent and 
      independent cascades to exert a wide spectrum of biological activities.
      Cardiovascular disorders such as abnormal angiogenesis, atherosclerosis,
      pulmonary hypertension and cardiac hypertrophy have been linked to aberrant BMP
      signalling. To correct the dysregulated BMP signalling in cardiovascular
      pathogenesis, it is essential to get a better understanding of how the regulators
      and effectors of BMP signalling control cardiovascular function and how the
      dysregulated BMP signalling contributes to cardiovascular dysfunction. We hence
      highlight several key regulators of BMP signalling such as extracellular
      regulators of ligands, mechanical forces, microRNAs and small molecule drugs as
      well as typical BMP effectors like direct downstream target genes, mitogen
      activated protein kinases, reactive oxygen species and microRNAs. The insights
      into these molecular processes will help target both the regulators and important
      effectors to reverse BMP-associated cardiovascular pathogenesis. 

PMID- 25952566
TI  - Outcome of Subcutaneous Implantable Cardioverter Defibrillator Implantation in
      Patients with End-Stage Renal Disease on Dialysis.
AB  - BACKGROUND: Although the subcutaneous ICD (S-ICD(r)) is an attractive alternative
      in patients with end-stage renal disease (ESRD), data on S-ICD outcomes in
      dialysis patients are lacking. METHODS: Patients with cardiomyopathy undergoing S
      ICD implantation in our center were stratified by need for chronic dialysis at
      the time of implant. The primary endpoint was incidence of death, heart failure
      hospitalization or appropriate S-ICD shocks, and secondary endpoints were
      incidence of inappropriate shocks or implant related complications requiring
      surgical re-intervention. Mean follow-up was longer in the nondialysis cohort
      (514 +/- 495 vs. 227 +/- 233 days, P = 0.006), so all endpoints were analyzed
      using time-dependent comparisons and reported as annual event rates. RESULTS: Out
      of 79 S-ICD implants included in this analysis, 27 patients were on dialysis.
      Dialysis patients were older and more likely to be diabetic. Mean ejection
      fraction across the entire cohort was 26.9% without significant difference
      between dialysis and nondialysis groups. Although not significant, the incidence
      of the primary endpoint was higher in the dialysis cohort (23.8%/year vs.
      10.9%/year, P = 0.317), driven primarily by a higher rate of appropriate shocks.
      The rate of inappropriate shocks was similar between groups (dialysis 6.0%/year
      vs. nondialysis 6.8%/year, P = 0.509). No patients in the dialysis cohort had
      complications requiring surgical re-intervention versus 6 patients in the
      nondialysis cohort (P = 0.086). CONCLUSIONS: Our data suggest that S-ICD
      implantation in dialysis patients is not associated with an excess risk of
      implant related complications or inappropriate shocks.

PMID- 25952568
TI  - Bayesian phylogeographic analyses clarify the origin of the HIV-1 subtype A
      variant circulating in former Soviet Union's countries.
AB  - The HIV-1 subtype A variant dominating the HIV-1 epidemics in former Soviet Union
      (FSU) countries (A(FSU)) represents one of the major clades of the HIV-1
      pandemic. This variant was reported to have begun spreading among injecting drug
      users (IDUs) in the Ukrainian city of Odessa in late 1994. Two competing
      hypotheses have been proposed on the ancestral origin of the A(FSU) variant,
      locating it either in the Democratic Republic of Congo (DRC) or in the Republic
      of Guinea (RG). The studies supporting these hypotheses employed phylogenetic
      analyses to identify HIV-1 sequences collected outside FSU countries ancestrally
      related to A(FSU). A different approach, based on Bayesian phylogenetic inference
      and coalescent-based population genetics, has been employed here to elucidate the
      ancestry of this HIV-1 variant and to improve our knowledge on its spread in FSU
      countries. The analyses were carried out using env (C2-V3-C3) and p24(gag)
      fragments of the HIV-1 genome. The inferred migration for the HIV-1 A(FSU)
      variant revealed only one significantly supported migration pathway from Africa
      to Eastern Europe, supporting the hypothesis of its origin in the DRC and
      estimating the upper limit of the migration of the ancestral virus from Africa
      around 1970. The support for an origin in the RG was negligible. The results
      supported the main role of Odessa as the epicenter of the A(FSU) epidemic, dating
      the tMRCA of the A(FSU) variant around 1984, ten years before its explosive
      expansion among IDUs. The estimated origin of the AFSU subcluster responsible for
      the IDU outbreak was also located in Odessa, with the estimated tMRCA around
      1993. Statistically supported migration routes from Odessa to other cities of
      Ukraine, Russia, Kazakhstan, Uzbekistan and Belarus were also inferred by the
      Bayesian phylogeographic analysis. These results shed new light on the origin and
      spread of the HIV-1 A(FSU) variant.

PMID- 25952567
TI  - Molecular inference of sources and spreading patterns of Plasmodium falciparum
      malaria parasites in internally displaced persons settlements in Myanmar-China
      border area.
AB  - In Myanmar, civil unrest and establishment of internally displaced persons (IDP)
      settlement along the Myanmar-China border have impacted malaria transmission. The
      growing IDP populations raise deep concerns about health impact on local
      communities. Microsatellite markers were used to examine the source and spreading
      patterns of Plasmodium falciparum between IDP settlement and surrounding villages
      in Myanmar along the China border. Genotypic structure of P. falciparum was
      compared over the past three years from the same area and the demographic history
      was inferred to determine the source of recent infections. In addition, we
      examined if border migration is a factor of P. falciparum infections in China by
      determining gene flow patterns across borders. Compared to local community, the
      IDP samples showed a reduced and consistently lower genetic diversity over the
      past three years. A strong signature of genetic bottleneck was detected in the
      IDP samples. P. falciparum infections from the border regions in China were
      genetically similar to Myanmar and parasite gene flow was not constrained by
      geographical distance. Reduced genetic diversity of P. falciparum suggested
      intense malaria control within the IDP settlement. Human movement was a key
      factor to the spread of malaria both locally in Myanmar and across the
      international border. 

PMID- 25952569
TI  - Full genomic characterization and phylogenetic analysis of a zoonotic human
      G8P[14] rotavirus strain detected in a sample from Guatemala.
AB  - We report the genomic characterization of a rare human G8P[14] rotavirus strain,
      identified in a stool sample from Guatemala (GTM) during routine rotavirus
      surveillance. This strain was designated as RVA/Human
      wt/GTM/2009726790/2009/G8P[14], with a genomic constellation of G8-P[14]-I2-R2-C2
      M2-A13-N2-T6-E2-H3. The VP4 gene occupied lineage VII within the P[14] genotype.
      Phylogenetic analysis of each genome segment revealed close relatedness to
      several zoonotic simian, guanaco and bovine strains. Our findings suggest that
      strain RVA/Human-wt/GTM/2009726790/2009/G8P[14] is an example of a direct
      zoonotic transmission event. The results of this study reinforce the potential
      role of interspecies transmission and reassortment in generating novel and rare
      rotavirus strains which infect humans. 

PMID- 25952570
TI  - In vivo sodium MR imaging of the abdomen at 3T.
AB  - PURPOSE: Transmembrane sodium ((23)Na) gradient is critical for cell survival and
      viability and a target for the development of anti-cancer drugs and treatment as
      it serves as a signal transducer. The ability to integrate abdominal (23)Na MRI
      in clinical settings would be useful to non-invasively detect and diagnose a
      number of diseases in various organ systems. Our goal in this work was to enhance
      the quality of (23)Na MRI of the abdomen using a 3-Tesla MR scanner and a novel 8
      channel phased-array dual-tuned (23)Na and (1)H transmit (Tx)/receive (Rx) coil
      specially designed to image a large abdomen region with relatively high SNR.
      METHODS: A modified GRE imaging sequence was optimized for (23)Na MRI to obtain
      the best possible combination of SNR, spatial resolution, and scan time in
      phantoms as well as volunteers. Tissue sodium concentration (TSC) of the whole
      abdomen was calculated from the inhomogeneity-corrected (23)Na MRI for absolute
      quantification. In addition, in vivo reproducibility and reliability of TSC
      measurements from (23)Na MRI was evaluated in normal volunteers. RESULTS: (23)Na
      axial images of the entire abdomen with a high spatial resolution (0.3 cm) and
      SNR (~20) in 15 min using the novel 8-channel dual-tuned (23)Na and (1)H
      transmit/receive coil were obtained. Quantitative analysis of the sodium images
      estimated a mean TSC of the liver to be 20.13 mM in healthy volunteers.
      CONCLUSION: Our results have shown that it is feasible to obtain high-resolution
      (23)Na images using a multi-channel surface coil with good SNR in clinically
      acceptable scan times in clinical practice for various body applications.

PMID- 25952571
TI  - Xanthogranulomatous cholecystitis: diagnostic performance of US, CT, and MRI for
      differentiation from gallbladder carcinoma.
AB  - OBJECTIVES: The purpose of this study is to evaluate the diagnostic performance
      of HRUS, CT, and MRI for differentiating xanthogranulomatous cholecystitis (XGC)
      from gallbladder (GB) cancer. MATERIALS AND METHODS: Patients with surgically
      proven XGC (n = 40) and GB cancer (n = 44), who had undergone at least one HRUS
      (n = 43), CT (n = 82), or MRI (n = 34) examination between 2000 and 2012, were
      included. Two radiologists retrospectively graded the likelihood of XGC or GB
      cancer using a 5-point confidence scale; they also assessed the imaging features.
      Statistical analyses were performed using ROC, ANOVA, and Fisher's exact test.
      RESULTS: Diagnostic performance of MRI was better than HRUS for differentiating
      XGC from GB cancer (AUCs = 0.867 and 0.911 vs. AUCs = 0.818 and 0.86). However,
      HRUS showed a better performance than CT (AUCs = 0.818 and 0.86 vs. AUCs = 0.806
      and 0.84) with moderate to excellent agreement (kappa = 0.48-0.83). Statistically
      common findings for XGC included non-focal thickening, smooth GB wall, presence
      of intramural nodules, type I enhancement of wall, transient hepatic attenuation
      difference, and continuity of mucosa (p < 0.05). Co-existence of gallstones (OR =
      16.5), non-focal thickening (OR = 14.7), and collapsed lumen (OR = 13.0) on HRUS,
      and type I enhancement on CT (OR = 3.52) were independently associated with XGC
      (p < 0.05). CONCLUSION: Although MRI showed a better performance than both HRUS
      and CT, HRUS showed a better performance than CT. The co-existence of gallstones,
      non-focal thickening, and collapsed lumen on HRUS was independently associated
      with XGC.

PMID- 25952572
TI  - Biphenotypic hepatic tumors: imaging findings and review of literature.
AB  - PURPOSE: To describe imaging findings in biphenotypic hepatic tumors (BPT) and a
      proposal for new imaging classification based on contrast-enhanced imaging.
      METHODS: Retrospective review of CT, MRI, PET/CT, and ultrasound findings in 39
      patients with histologically confirmed BPT was performed. Tumor markers including
      AFP, L3 fraction, CA 19.9, CA 125, and CEA were recorded. Based on the dynamic
      enhancement features, BPT were categorized into 4 enhancement patterns (Types 1
      4). Enhancement patterns were correlated with other imaging findings and tumor
      markers. Imaging features and tumor markers that were not consistent with
      diagnosis of hepatocellular carcinoma or intrahepatic cholangiocarcinoma based on
      enhancement pattern were considered discordant findings. RESULTS: Enhancement
      patterns in 29 patients (CT/MR) included 23 Type 2 (continuous peripheral rim of
      late arterial hyperenhancement with washout or fade in portal venous and/or
      delayed phases, +/-delayed central enhancement) and 2 of each Types 1, 2, and 3.
      Discordant imaging findings were present in two patients with Type 2 pattern and
      in one patient with Type 1 pattern. Both AFP and CA 19.9 were elevated in 15 of
      33 of patients. Tumor markers AFP and CA 19.9 were discordant in 17 of 21
      patients with Type 2 pattern, two of two patients with Type 3 pattern. Most BPTs
      were markedly PET avid with average SUV max of 8.2. Most frequent ultrasound
      appearance is peripheral hypoechogenicity and central hyperechogenicity.
      CONCLUSIONS: BPT most commonly present with imaging features similar to
      cholangiocarcinoma or metastases. BPT can be suggested when imaging findings or
      tumor markers are discordant with the most likely diagnosis based on enhancement
      pattern.

PMID- 25952573
TI  - 'It's all foreign to me': how to decipher gastrointestinal intraluminal foreign
      bodies.
AB  - In evaluating the gastrointestinal tract, whether in the emergency room setting,
      the inpatient setting or the outpatient setting, the radiologist may encounter a
      myriad of intraluminal radio-opaque, non-anatomic entities. It is the
      radiologist's role to distinguish between true foreign bodies and medical
      paraphernalia. Further, the later must be evaluated for proper positioning vs.
      improper, potentially detrimental positioning. While many foreign bodies from the
      community may be distinctly familiar to the radiologist, the large variety of
      medical tools in existence may not be. Furthermore, many medical devices are
      designed to transiently traverse, or interact with the gastrointestinal tract,
      requiring the radiologist to become familiar with their natural history. We
      explore a select group of common and uncommon intraluminal foreign bodies and
      will divide them into medical paraphernalia that are properly positioned; medical
      paraphernalia that are in abnormal locations and miscellaneous foreign bodies
      from the community. For each medical tool, we will discuss its development and
      medical utility, natural history as it relates to the gastrointestinal tract,
      optimal positioning as assessed radiologically, malpositioning, and subsequent
      complications. A small selection of unusual foreign bodies from the community
      will be presented. Finally, a selection of medical conditions which produce
      symptoms due to acquired intraluminal objects will be reviewed. 

PMID- 25952574
TI  - Multimodality fusion imaging in abdominal and pelvic malignancies: current
      applications and future perspectives.
AB  - Medicine is evolving toward personalized care and this development entails the
      integration, amalgamation, and synchronized analysis of data from multiple
      sources. Multimodality fusion imaging refers to the simultaneous visualization of
      spatially aligned and juxtaposed medical images obtained by two or more image
      modalities. PET/MRI scanners and MMFI platforms are able to improve the
      diagnostic workflow in oncologic patients and provide exquisite images that aid
      physicians in the molecular profiling and characterization of tissues. Advanced
      navigation platforms involving real-time ultrasound are promising tools for
      guiding personalized and tailored mini-invasive interventional procedures on
      technically challenging targets. The main objective of the present essay was to
      describe the current applications and future perspectives of multimodality fusion
      imaging for both diagnostic and interventional purposes in the field of abdominal
      and pelvic malignancies. We also outlined the technical differences between
      fusion imaging achieved by means of simultaneous bimodal acquisition (i.e.,
      integrated PET/MRI scanners), retrospective co-registration, and multimodality
      fusion imaging involving ultrafast or real-time imaging modalities. 

PMID- 25952575
TI  - The "jackstone" appearance.

PMID- 25952576
TI  - Liver parenchyma at the site of hypodense parafissural pseudolesion contains
      increased collagen.
AB  - PURPOSE: To identify a histological substrate explaining the hypodense
      pseudolesion in the liver at the right side of the falciform ligament and the
      correlation with CT radiodensity. MATERIALS AND METHODS: Tissue specimens were
      obtained from the right (pseudolesion) and left (control) side of the falciform
      ligament at the level of the left portal vein, in deceased adults during autopsy.
      Radiodensity was measured at the same locations at CT. Digital image analysis
      determined the amount of collagen and fat in histological sections, and the
      number of portal triads and central veins were counted. Glycogen content was
      visually assessed by the area percentage of the histological section. RESULTS:
      Specimens from 17 patients showed a 39% increase in collagen for the site of the
      pseudolesion compared to the contralateral side (p = 0.08). No significant
      differences were found for the amount of fat, glycogen, portal triads, or central
      veins. In one patient a pseudolesion was visible on CT, and this contained 52%
      more collagen than the control side. CONCLUSION: The pseudolesion at the right
      parafissural side in the liver contains more collagen compared to the control
      left side, while there is no difference in fat or glycogen content or number of
      portal and hepatic veins. Collagen may be the cause of the pseudolesion.

PMID- 25952577
TI  - Impact of child and family characteristics on cerebral palsy treatment.
AB  - AIM: The aim of the study was to describe the relationship between the child's
      and family's characteristics and the most common treatment modalities in a
      national population-based sample of 8- to 15-year-old children with cerebral
      palsy. METHOD: A cross-sectional study, based on the Danish Cerebral Palsy
      Registry. The parents of 462 children answered a questionnaire about their
      child's treatment and the family's characteristics (living with a single parent,
      having siblings, living in a city, parental education level). Descriptive and
      logistic regression analyses were performed for every treatment modality,
      stratified by Gross Motor Function Classification System (GMFCS) level. RESULTS:
      An IQ below 85 was associated with weekly therapy in GMFCS level I (adjusted odds
      ratio [ORadj ] 2.5 [CI 1.1-5.7]) and the use of oral spasmolytics in GMFCS levels
      III to V (ORadj 3.1 [CI 1.3-7.4]). Older children in GMFCS levels III to V used
      daily orthoses less frequently (ORadj 0.7 [CI 0.6-0.9] per year). Of all of the
      family characteristics studied, only the parents' education level had significant
      associations with more than one treatment modality. INTERPRETATION: A child's
      cognitive function showed an impact on treatment of the motor impairment in
      children 8 to 15 years of age with cerebral palsy. Parental education level may
      influence the choice of treatment.

PMID- 25952578
TI  - A Simple Primary Amine Catalyst for Enantioselective alpha-Hydroxylations and
      alpha-Fluorinations of Branched Aldehydes.
AB  - A new primary amine catalyst for the asymmetric alpha-hydroxylation and alpha
      fluorination of alpha-branched aldehydes is described. The products of the title
      transformations are generated in excellent yields with high enantioselectivities.
      Both processes can be performed within short reaction times and on gram scale.
      The similarity in results obtained in both reactions, combined with computational
      evidence, implies a common basis for stereoinduction and the possibility of a
      general catalytic mechanism for alpha-functionalizations. Promising initial
      results in alpha-amination and alpha-chlorination reactions support this
      hypothesis. 

PMID- 25952579
TI  - A new paradigm in treatment of brain metastases.

PMID- 25952580
TI  - The relationship between altered mitochondrial DNA copy number and cancer risk: a
      meta-analysis.
AB  - Currently, a comprehensive assessment between mitochondrial DNA (mtDNA) content
      and cancer risk is lacking. We designed this meta-analysis to test the hypothesis
      that altered mtDNA copy number might influence genetic susceptibility to some
      specific types of cancer. The processes of literature search, eligibility
      appraisal and data retrieval were independently completed in duplicate. The mtDNA
      copy number which was dichotomized or classified into tertiles was compared
      between cancer cases and controls. Twenty-six articles with 38 study groups were
      analyzed among 6682 cases and 9923 controls. When dichotomizing mtDNA copy number
      at the median value, there was an 11% increased cancer risk for carriers of high
      mtDNA content (P = 0.320). By cancer type, high mtDNA content was associated with
      an increased risk for lymphoma (OR = 1.76; P = 0.023) but a reduced risk for
      skeleton cancer (OR = 0.39; P = 0.001). Carriers of the 2(nd) and 3(rd) tertiles
      of mtDNA copy number had an 1.74-fold (P = 0.010) and 2.07-fold (P = 0.021)
      increased risk of lymphoma, respectively. By contrast, there was correspondingly
      a 56% (P < 0.001) and 80% (P < 0.001) reduced risk of skeleton cancer. Our
      findings suggested that elevated mtDNA content was associated with a higher risk
      for lymphoma, but a lower risk for skeleton cancer. 

PMID- 25952581
TI  - Prevalence of non-suicidal self-injury and distinct groups of self-injurers in a
      community sample of adolescents.
AB  - PURPOSE: Adolescence is an important developmental period for the first onset of
      non-suicidal self-injury (NSSI), a behavior known to be associated with elevated
      suicide risk. Little is currently known, however, about NSSI among adolescents.
      The primary objectives of this research were to establish the prevalence of non
      suicidal self-injury (NSSI) in a representative sample of Turkish high school
      students and to identify and describe distinct subgroups of self-injurers.
      METHODS: A total of 1656 of 1676 eligible students (98.8 % participation rate)
      from 18 schools were surveyed during the 2010-2011 academic year. Questionnaires
      were administered that assessed prior engagement in a variety of self-injurious
      behaviors, current psychiatric symptoms, suicide-related risk factors, and
      participation in health-risk behaviors. Latent class analysis (LCA) methods were
      used to identify distinct groups of self-injurers. RESULTS: Almost one-third of
      the sample (N = 519) endorsed some previous engagement in NSSI behaviors. In LCA
      analyses restricted to youth with prior histories of NSSI, four distinct classes
      were identified characterized by: (1) low rates of NSSI behaviors (29 %); (2)
      high rates of self-battery (32 %); (3) high rates of self-cutting (19 %); and (4)
      high rates of multiple NSSI behaviors (19 %). These classes were further
      distinguished by current psychiatric symptoms, suicide risk factors, and other
      health-risk behaviors. CONCLUSIONS: Findings from the present study indicate that
      NSSI is a common form of behavior among adolescent youth. There is, however,
      considerable heterogeneity among those with NSSI histories, with about 40 % at
      particularly high risk for ongoing distress, future acts of intentional self
      harm, and suicidal behavior.

PMID- 25952583
TI  - Endocrine sequelae beyond 10 years in survivors of medulloblastoma.
AB  - INTRODUCTION: Survival following treatment of paediatric medulloblastomas has
      significantly improved over the past few decades, but as a consequence, late
      effects, particularly endocrine sequelae, have been recognized. The complete
      picture of late effects, however, has been limited by short duration of follow
      up. AIM: To establish the evolution of endocrine sequelae in patients treated for
      medulloblastoma. METHODS: Single-centre analysis of medulloblastoma treatment and
      endocrine sequelae in patients diagnosed between 1982 and 2002. RESULTS: A total
      of 109 patients were treated for medulloblastoma, with various treatment
      modalities involving radio- and chemotherapy. Only 45 (41%) patients remained
      alive, and details of treatment and late effects were available for 35 (25 m).
      The median age at diagnosis was 8 (range 2-14) years, and the median follow-up
      was 18 (range 10-28) years. Growth hormone deficiency (GHD) was the most
      prevalent hormone deficiency (97%), followed by primary hypothyroidism (60%) and
      adrenocorticotrophic hormone (ACTH) deficiency (45.5%). The median time from end
      of treatment to loss of growth hormone was 1.7 (range 0.7-15) years, ACTH
      deficiency 2.9 (range 0.75-7.5) years and hypothyroidism 4.1 (range 0.7-11.4)
      years. Twenty-three percentage developed hypogonadism (17% primary and 6%
      secondary), whilst precocious puberty was seen in 20%. Endocrinopathies appeared
      to be more prevalent in those treated with concomitant chemotherapy and
      radiotherapy. CONCLUSIONS: Prevalence of endocrine sequelae in medulloblastoma
      survivors is high, and evolution of endocrine dysfunction can occur as late as 15
      years from treatment completion; hence, long-term close monitoring of growth,
      puberty and gonadal function is essential.

PMID- 25952584
TI  - Bilateral spontaneous atraumatic rupture of the Achilles tendon in an athlete.
AB  - We report a case of spontaneous, bilateral Achilles rupture in a 33-year-old man
      with no specific risk factors. The rupture occurred after a heavy impact during a
      sports activity, and although the rupture was painful, he was able to mobilize
      slowly. After a clinical examination confirmed the diagnosis, ultrasonography and
      magnetic resonance imaging evaluation of the Achilles tendons revealed bilateral
      ruptures. The patient underwent bilateral conservative treatment and subsequently
      embarked on a comprehensive rehabilitation program with a good functional outcome
      at follow-up. The patient's return to premorbid work and social life was
      uneventful. A spontaneous rupture in a patient without any predisposing risk
      factors is uncommon, and for it to occur bilaterally is notably rare.

PMID- 25952582
TI  - Significances of contactin-1 expression in human gastric cancer and knockdown of
      contactin-1 expression inhibits invasion and metastasis of MKN45 gastric cancer
      cells.
AB  - PURPOSE: Contactin-1 (CNTN-1) has been shown to promote cancer metastasis.
      Previously, we have reported that the expression of CNTN-1 was upregulated in
      gastric cancer tissues compared with adjacent normal tissues. Here, we
      investigated the significance of CNTN-1 expression and its underlying mechanism
      of metastasis mediated by epithelial-mesenchymal transition (EMT) in gastric
      cancer. METHODS: The expressions of CNTN-1 and EMT-related proteins were assayed
      through immunohistochemical staining of pathological specimens from patients with
      gastric cancer. Other methods including reverse transcriptase polymerase chain
      reaction, Western blotting, stably transfected against CNTN-1 into MKN45 cells,
      migration and invasion assays in vitro and nude mouse tumorigenicity in vivo were
      also utilized. RESULTS: The results revealed that CNTN-1 expression was elevated
      and positively correlated with metastasis, EMT-related markers and poor prognosis
      in patients with gastric cancer. Moreover, CNTN-1 expression might associate with
      invasive ability to some extent in gastric cancer cell lines KATO-SH, SGC7901 and
      MKN45. Knockdown of CNTN-1 expression in MKN45 cells using short hairpin RNA
      (shRNA) had notable effects on cell migration and invasion, rather than
      proliferation in vitro and in vivo. Furthermore, suppression of CNTN-1 expression
      altered EMT through inhibition of transcription factor Slug, rather than Snail.
      CONCLUSION: Our study demonstrated that the elevated CNTN-1 expression closely
      correlated with cancer metastasis and patient survival, and its functions seemed
      to be important in migration and invasion of gastric cancer cells via EMT
      alteration probably mediated by inhibition of Slug. CNTN-1 may be a potential
      therapeutic target for gastric cancer.

PMID- 25952586
TI  - Video-games used in a group setting is feasible and effective to improve
      indicators of physical activity in individuals with chronic stroke: a randomized
      controlled trial.
AB  - OBJECTIVES: To investigate the feasibility of using video-games in a group
      setting and to compare the effectiveness of video-games as a group intervention
      to a traditional group intervention for improving physical activity in
      individuals with chronic stroke. DESIGN: A single-blind randomized controlled
      trial with evaluations pre and post a 3-month intervention, and at 3-month follow
      up. Compliance (session attendance), satisfaction and adverse effects were
      feasibility measures. Grip strength and gait speed were measures of physical
      activity. Hip accelerometers quantified steps/day and the Action Research Arm
      Test assessed the functional ability of the upper extremity. RESULTS: Forty-seven
      community-dwelling individuals with chronic stroke (29-78 years) were randomly
      allocated to receive video-game (N=24) or traditional therapy (N=23) in a group
      setting. There was high treatment compliance for both interventions (video-games
      78%, traditional therapy-66%), but satisfaction was rated higher for the video
      game (93%) than the traditional therapy (71%) (chi(2)=4.98, P=0.026). Adverse
      effects were not reported in either group. Significant improvements were
      demonstrated in both groups for gait speed (F=3.9, P=0.02), grip strength of the
      weaker (F=6.67, P=0.002) and stronger hands (F=7.5, P=0.001). Daily steps and
      functional ability of the weaker hand did not increase in either group.
      CONCLUSIONS: Using video-games in a small group setting is feasible, safe and
      satisfying. Video-games improve indicators of physical activity of individuals
      with chronic stroke.

PMID- 25952585
TI  - FRAMEWORK FOR USER INVOLVEMENT IN HEALTH TECHNOLOGY ASSESSMENT AT THE LOCAL
      LEVEL: VIEWS OF HEALTH MANAGERS, USER REPRESENTATIVES, AND CLINICIANS.
AB  - OBJECTIVES: The aim of this study was to explore stakeholders' points of views
      regarding the applicability and relevance of a framework for user involvement in
      health technology assessment (HTA) at the local level. We tested this framework
      in the context of the assessment of alternative measures to restraint and
      seclusion among hospitalized adults and those living in long-term-care
      facilities. METHODS: Twenty stakeholders (health managers, user representatives,
      and clinicians) from seven regions of Quebec participated in a semi-structured
      interview. A thematic analysis of the transcribed interviews was performed.
      RESULTS: The findings highlighted the relevance and applicability of the
      framework to this specific HTA. According to interviewees, direct participation
      of users in the HTA process allows them to be part of the decision-making
      process. User consultation makes it possible to consider the views of a wide
      variety of people, such as marginalized and vulnerable groups, who do not
      necessarily meet the requirements for participating in HTA committees. However,
      some user representatives emphasized that user consultation should be integrated
      into a more holistic and participatory perspective. The most frequent barrier
      associated with user involvement in HTA was the top-down health system, which
      takes little account of the user's perspective. CONCLUSIONS: The proposed
      framework was seen as a reference tool for making practitioners and health
      managers aware of the different mechanisms of user involvement in HTA and
      providing a structured way to classify and describe strategies. However, there is
      a need for more concrete instruments to guide practice and support decision
      making on specific strategies for user involvement in HTA at the local level.

PMID- 25952587
TI  - A New Zealand pilot randomized controlled trial of a web-based interactive self
      management programme (MSInvigor8) with and without email support for the
      treatment of multiple sclerosis fatigue.
AB  - OBJECTIVE: To pilot and compare the efficacy of an internet-based cognitive
      behavioural therapy self-management programme with (MSInvigor8-Plus) and without
      (MSInvigor8-Only) the use of email support in reducing fatigue severity and
      impact (primary outcomes), and depressed and anxious mood (secondary outcomes).
      DESIGN: Randomized controlled trial using an independent randomization system
      built into the website and intention-to-treat analysis. SETTING: Participants
      were recruited through the local Multiple Sclerosis Society and hospital
      neurological services in New Zealand. SUBJECTS: A total of 39 people (aged 31-63
      years), experiencing multiple sclerosis fatigue, able to walk with and without
      walking aids, were randomized to MSInvigor8-Only (n = 20) or to MSInvigor8-Plus
      (n = 19). INTERVENTIONS: MSInvigor8 is an eight-session programme based on
      cognitive behaviour therapy principles including psycho-education, self
      monitoring, and changing unhelpful activity and thought patterns. MAIN MEASURES:
      Outcome measures included fatigue severity (Chalder Fatigue Scale) and impact
      (Modified Fatigue Impact Scale), and anxiety and depression (Hospital Anxiety and
      Depression Scale). Assessments were performed at baseline and at 10 weeks.
      RESULTS: The MSInvigor8-Plus condition resulted in significantly greater
      reductions in fatigue severity (F [1,36] = 9.09, p < 0.01) and impact (F [1,36] =
      6.03, p < 0.02) compared with the MSInvigor8-Only condition. Large between-group
      effect sizes for fatigue severity (d = 0.99) and fatigue impact (d = 0.81) were
      obtained. No significant differences were found between the groups on changes in
      anxiety and depression. CONCLUSIONS: MSInvigor8 delivered with email-based
      support is a potentially promising, acceptable, and cost-effective approach to
      treating fatigue in people with multiple sclerosis in New Zealand.

PMID- 25952588
TI  - Toward an evidence-based patient-provider communication in rehabilitation:
      linking communication elements to better rehabilitation outcomes.
AB  - BACKGROUND: There is a growing interest in linking aspects of patient-provider
      communication to rehabilitation outcomes. However, the field lacks a conceptual
      understanding on: (a) 'how' rehabilitation outcomes can be improved by
      communication; and (b) through 'which' elements in particular. This article
      elaborates on the conceptual developments toward informing further practice and
      research. METHODS: Existing models of communication in healthcare were adapted to
      rehabilitation, and its outcomes through a comprehensive literature review.
      RESULTS: After depicting mediating mechanisms and variables (e.g. therapeutic
      engagement, adjustment toward disability), this article presents the '4 Rehab
      Communication Elements' deemed likely to underpin rehabilitation outcomes. The
      four elements are: (a) knowing the person and building a supportive relationship;
      (b) effective information exchange and education; (c) shared goal-setting and
      action planning; and (d) fostering a more positive, yet realistic, cognitive and
      self-reframing. DISCUSSION: This article describes an unprecedented, outcomes
      oriented approach toward the design of rehabilitation communication, which has
      resulted in the development of a new intervention model: the '4 Rehab
      Communication Elements'. Further trials are needed to evaluate the impact of this
      whole intervention model on rehabilitation outcomes.

PMID- 25952590
TI  - Is the practice of goal-setting for patients in acute stroke care patient-centred
      and what factors influence this? A qualitative study.
AB  - OBJECTIVE: To explore whether goal-setting for rehabilitation with acute stroke
      survivors is patient-centred and identify factors which influence the adoption of
      patient-centredness in goal-setting practice. SETTING: Acute stroke unit in a
      large teaching hospital in England. PARTICIPANTS: Patients with stroke who had no
      cognitive or significant communication problems and health care professionals who
      had a significant engagement with an individual patient were approached for
      participation. METHOD: Multiple qualitative methods were used. Perceptions and
      beliefs about patient-centredness, within the context of goal-setting, were
      collected from patients and corresponding professionals using qualitative semi
      structured interviews. Adoption of patient-centred behaviour was triangulated
      using analysis of patient records and observation of team meetings related to
      participating patients. DATA ANALYSIS: Interview transcripts and field notes were
      coded, clustered under categories and descriptively summarised. Additionally,
      data from patients' documents were summarised. These summaries were then mapped
      on to an a-priori frame work of patient-centredness from which further
      interpretative themes were derived. RESULTS: Seven patients and seven health-care
      professionals participated. Goal-setting was not consistently patient-centred as
      evidenced by a) incongruities between patients and professionals in setting,
      communicating and prioritising of goals and b) dysfunctional therapeutic
      relationships. The factors that influenced patient-centred goal-setting were both
      professional and patient beliefs and attributes, work-culture, practice model,
      limitations in knowledge and systems that disempowered both professionals and
      patients. CONCLUSION: It may be possible to infer that current local practice of
      goal-setting was inadequately patient-centred. Further research is required to
      identify strategies to overcome these challenges and to develop patient-centred
      goal-setting methods.

PMID- 25952589
TI  - Comparing treatment fidelity between study arms of a randomized controlled
      clinical trial for stroke family caregivers.
AB  - OBJECTIVE: To compare treatment fidelity among treatment arms in the Telephone
      Assessment and Skill-Building Kit study for stroke caregivers (TASK II) with
      respect to: 1) protocol adherence; 2) intervention dosage and 3) nurse intervener
      perspectives. DESIGN: A randomized controlled clinical trial design. SETTING:
      Urban, community, midwestern United States. SUBJECTS: A total of 254 stroke
      caregivers (mean +/-SD age, 54.4 +/-11.8 years), 55 (22.0%) males and 199 (78.4%)
      females) randomized to the TASK II intervention (n=123) or an Information,
      Support, and Referral comparison group (n=131). INTERVENTIONS: TASK II
      participants received the TASK II Resource Guide; Information, Support, and
      Referral participants received a standard caregiver brochure. At approximately 8
      weeks after discharge, both groups received 8 weekly calls from a nurse, with a
      booster call 4 weeks later. MEASURES: Protocol adherence was evaluated with the
      TASK II Checklist for Monitoring Adherence. Intervention dosage was measured by
      the number of minutes caregivers spent reading materials and talking with the
      nurse. Nurse intervener perspectives were obtained through focus groups. RESULTS:
      Protocol adherence was 80% for the TASK II and 92% for the Information, Support,
      and Referral. As expected, intervention dosage differed between TASK II and
      Information, Support, and Referral with respect to caregiver time spent reading
      materials (t=-6.49; P<.001) and talking with the nurse (t=-7.38; P<.001). Focus
      groups with nurses yielded further evidence for treatment fidelity and
      recommendations for future trials. CONCLUSIONS: These findings substantiate
      treatment fidelity in both study arms of the TASK II stroke caregiver
      intervention trial (NIH R01NR010388; ClinicalTrials.govNCT01275495).

PMID- 25952591
TI  - Effects of additional, dynamic supported standing practice on functional recovery
      in patients with sub-acute stroke: a randomized pilot and feasibility trial.
AB  - OBJECTIVE: To evaluate the feasibility and preliminary effectiveness of
      additional dynamic versus static passive standing performed by patients with sub
      acute stroke supervised by trained helpers. DESIGN: Assessor blinded, randomized
      pilot and feasibility trial. SETTING: Neurological rehabilitation centre.
      PARTICIPANTS: Non-ambulatory participants in the sub-acute phase after stroke.
      INTERVENTION: Usual care plus additional standing training, consisting of either
      dynamic standing practice in a modified standing frame (intervention group, n=14)
      or static standing practice in a conventional standing frame (control group,
      n=14) for 5 weeks. MAIN MEASURES: Feasibility was assessed through occurrence of
      adverse events, patient satisfaction and operability of the technical device
      handled by trained helpers. Preliminary effectiveness was assessed with the Berg
      Balance Scale (primary outcome) and other measures of physical functioning.
      RESULTS: Trained helpers were capable to apply the intervention, and no adverse
      events occurred. Both groups were comparable at baseline. Within-group changes
      tended to be higher for the intervention group, but did not reach a significant
      level except for the Functional Ambulation Categories. Specifically, median pre
      post improvements in the Berg Balance Scale tended to be higher in the dynamic
      (20, inter quartile range (IQR): 2-33 points) than in the static standing group
      (4.5, IQR: 0-16 points; U=62; P=0.052; effect size=0.478). CONCLUSIONS: In
      severely affected individuals after stroke, dynamic supported standing practice
      can be performed safely by trained helpers. In a larger-scale phase III study, a
      total of 116 patients would be needed to prove the preliminary effectiveness
      found in this study.

PMID- 25952592
TI  - Characterization of Complementary and Alternative Medicine-Related Consultations
      in an Academic Drug Information Service.
AB  - PURPOSE: To characterize requests received through an academic drug information
      consultation service related to complementary and alternative medicines. METHODS:
      A retrospective review and descriptive analysis of drug information consultations
      was conducted. RESULTS: A total of 195 consultations related to complementary and
      alternative medicine were evaluated. All consultation requests involved questions
      about dietary supplements. The most common request types were related to safety
      and tolerability (39%), effectiveness (38%), and therapeutic use (34%). Sixty
      eight percent of the requests were from pharmacists. The most frequent
      consultation requests from pharmacists were questions related to drug
      interactions (37%), therapeutic use (37%), or stability/compatibility/storage
      (34%). Nearly 60% of complementary and alternative medicine-related consultation
      requests were able to be completely addressed using available resources. Among
      review sources, Natural Medicines Comprehensive Database, Clinical Pharmacology,
      Micromedex, and Pharmacist's Letter were the most common resources used to
      address consultations. CONCLUSION: Utilization of a drug information service may
      be a viable option for health care professionals to help answer a complementary
      and alternative medicine-related question. Additionally, pharmacists and other
      health care professionals may consider acquiring resources identified to
      consistently answering these questions.

PMID- 25952593
TI  - Vedolizumab: A New Opponent in the Battle Against Crohn's Disease and Ulcerative
      Colitis.
AB  - Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders affecting
      the gastrointestinal (GI) tract that encompass Crohn's disease (CD) and
      ulcerative colitis (UC). In these disease states, epithelial damage of the
      intestinal mucosa is evident due to increased lymphocyte trafficking to the area,
      which affects the normal intestinal barrier function. Currently available
      pharmacotherapy can be limited in terms of efficacy and associated toxicities.
      Newer agents have emerged, including the monoclonal antibody natalizumab, which
      antagonizes integrin, an important component within the inflammation cascade.
      Natalizumab works by modulating both the GI and brain biologic responses and as a
      result there is risk of the opportunistic infection known as progressive
      multifocal leukoencephalopathy (PML), putting patients at risk for severe
      disability and death. Vedolizumab, another integrin inhibitor, is selective for
      modulating the gut biologic response but not the brain, consequently decreasing
      the risk for PML. To generate information regarding the role of vedolizumab in
      the treatment of IBD, a literature search was conducted, yielding 7 phase I to
      III clinical trials. This article serves as a summary of efficacy, safety, and
      other relevant information from clinical studies to explore the role of
      vedolizumab in the treatment of CD and UC. 

PMID- 25952594
TI  - Glucose Disturbances and Atypical Antipsychotic Use in the Intensive Care Unit.
AB  - PURPOSE: Chronic use of atypical antipsychotics may lead to metabolic
      abnormalities including hyperglycemia. Although evidence supports acute
      hyperglycemic episodes associated with atypical antipsychotic use, the acute use
      of atypical antipsychotics in the intensive care unit (ICU) setting has not been
      studied. The purpose of this study is to evaluate the occurrence of hyperglycemia
      in ICU patients receiving newly prescribed atypical antipsychotic. SUMMARY: Of
      the 273 patient charts reviewed, 50 patients were included in this study.
      Approximately 45% of patients experienced at least 1 hyperglycemic episode (blood
      glucose >180 mg/dL) after the initiation of an atypical antipsychotic in the ICU.
      Of the patients experiencing at least 1 hyperglycemic episode, 60% experienced
      multiple distinct hyperglycemic episodes. In this study, quetiapine was the most
      commonly used atypical antipsychotic, 19 (38%) patients were discharged from the
      ICU on the atypical antipsychotic, 6 (12%) patients died in the ICU, and 31 (62%)
      patients were treated with an antihyperglycemic agent. Logistic regression
      analysis showed that women and ICU patients with a higher Acute Physiology and
      Chronic Health Evaluation II (APACHE II) score were significantly more likely to
      have multiple hyperglycemic episodes. CONCLUSION: Patients admitted to the ICU
      and initiated on an atypical antipsychotic may develop hyperglycemia independent
      of other glucose-elevating factors. The direct correlation of these agents to
      resulting acute hyperglycemia is unknown. Further studies are needed to
      investigate the link between atypical antipsychotics and acute hyperglycemia and
      the clinical significance of the impact on patient outcomes.

PMID- 25952595
TI  - Community- versus nosocomial-acquired severe sepsis and septic shock in patients
      admitted to a tertiary intensive care in Saudi Arabia, etiology and outcome.
AB  - BACKGROUND: Sepsis syndrome is a major worldwide cause of morbidity and
      mortality. While community-acquired severe sepsis and septic shock constitutes a
      major cause of admission to the intensive care unit, hospital-acquired severe
      sepsis and septic shock remain major preventable causes of ICU admission. This
      study evaluates the rate, etiology, complication and outcome of community- and
      hospital-acquired sepsis in a tertiary care hospital in Saudi Arabia. METHOD:
      This is a retrospective evaluation of all admissions with severe sepsis and
      septic shock to a general intensive care unit over a period of six months.
      RESULTS: A total number of 96 patients were included, which represented 15% of
      the total number of admissions during the study period. The mean age was 57.4 (SD
      21). Sixty percent of cases were due to hospital-acquired infections, and 40%
      were community-acquired. The majority of the infections acquired in the hospital
      occurred in medical wards and intensive care units (27% and 21%, respectively).
      At least one co-morbid condition was present in 94% of the sample patients, with
      cardiovascular disease and diabetes being the most frequently encountered
      disorders (58%). Both community and hospital-acquired severe sepsis and septic
      shock carry very high mortality (58%). The ICU length of stay was significantly
      longer for hospital and ICU acquired infections. CONCLUSION: Both community and
      hospital-acquired infections carry high mortality. Hospital-acquired severe
      sepsis is frequent in medical wards and ICUs, and measures to further evaluate
      risk factors are prudent.

PMID- 25952596
TI  - Endothelial Progenitor Cells as a Biomarker for Transitional Phenotypes in
      Hypertension.

PMID- 25952597
TI  - [Descriptive statistical analysis of the treatment of status epilepticus in a
      referral hospital].
AB  - INTRODUCTION: Status epilepticus is defined as either recurring seizures without
      regaining consciousness between them or one single seizure lasting more than 30
      minutes. AIMS: To perform a descriptive analysis of the most relevant data on the
      patients with status epilepticus who were admitted to a paediatric intensive care
      unit (PICU) and to review the risk factors associated to status epilepticus with
      a poor prognosis. PATIENTS AND METHODS: A study was conducted of the main
      variables of the patients with status epilepticus hospitalised in the PICU of a
      tertiary hospital over a period of six years. RESULTS: Data were collected on a
      total of 68 patients (55.9% males), the mean age being 3.7 years. The most
      frequent signs and symptoms were generalised tonic-clonic seizures (50%). The
      mean duration of the status epilepticus was 51.44 minutes. The mean number of
      antiepileptic drugs used to stem the seizures was 3.21 and the mean number of
      drugs used prior to admission to the PICU was 2.37. The most commonly used first
      choice drug was diazepam (83.8%) administered rectally (75%), followed by
      intravenous diazepam (52.9%) in second place and phenytoin was the most
      frequently used drug as the third choice. The most usual cause of status
      epilepticus was having previously suffered from epilepsy (33.9%), and Dravet's
      syndrome was the most frequent epileptic causation. CONCLUSIONS: Treatment of
      status epilepticus is complex and requires multidisciplinary and personalised
      management. Protocols and clinical guidelines need to be drawn up and reviewed to
      achieve an adequate management of these patients.

PMID- 25952598
TI  - [Functional assessment for people unable to walk due to spinal muscular atrophy
      and Duchenne muscular dystrophy. Translation and validation of the Egen
      Klassifikation 2 scale for the Spanish population].
AB  - INTRODUCTION: The Egen Klassifikation 2 Scale (EK2), expansion of the EK scale,
      assesses the functional capacity of people with spinal muscular atrophy (SMA) and
      Duchenne muscular dystrophy (DMD) that are in wheelchair phase. This version is
      more specific for SMA than its EK predecessor. AIM: To examine the validity and
      reliability of the Spanish version of the scale as a tool for measuring the
      functional capacity in patients with DMD and SMA who are in wheelchairs. PATIENTS
      AND METHODS: First, a translation-back-translation into Spanish of the English
      version of the EK2 was performed; later, we studied the reliability of the
      translated version. For this, 39 patients, aged between 4 and 60, who were
      evaluated by two observers, were recruited. To evaluate the intra-observer
      consistency, two assessments by the same observer were performed, and the inter
      observer third assessment was performed by a second observer. RESULTS: The
      obtained values based on the total score of the scale items (sum EK2) reflect
      excellent intra- and inter-observer reliability, 0.993 and 0.988 respectively.
      Also, for each of the items, reliability was excellent except for one item in
      which it was good. CONCLUSIONS: The Spanish version of the EK2 scale is a valid
      and reliable instrument for the Spanish population as a tool for measuring the
      functional capacity in patients with SMA and DMD who are in wheelchairs.

PMID- 25952599
TI  - [Reversible cortical atrophy secondary to anti-NMDA receptor antibody
      encephalitis].
AB  - INTRODUCTION: Anti-N-methyl-D-aspartate (NMDA) receptor antibody encephalitis was
      initially described as a paraneoplastic syndrome associated to ovarian teratomas.
      Yet, an increasing number of reports are being published involving cases of young
      women and children with signs and symptoms of an autoimmune encephalopathy, in 40
      50% of the cases secondary to a viral infection. Clinically, it is characterised
      by a progressive picture of psychiatric manifestations, convulsive seizures,
      dyskinesias and dysautonomias. One neuroimaging finding that has received little
      attention is reversible cortical atrophy, the underlying mechanism of which is
      unknown. CASE REPORT: We report the case of a 6-year-old girl who started with
      focal convulsive seizures, with an abnormal epileptogenic electroencephalogram
      and an initial tomography scan of the head that was normal. Anticonvulsive
      treatment was established. At three weeks new convulsive seizures, psychiatric
      manifestations and disorders in the sleep-arousal cycle appeared. Suspecting a
      case of anti-NMDA antibody receptor encephalitis, analyses were performed to test
      for the presence of these antibodies in serum and in cerebrospinal fluid, the
      results being positive. Magnetic resonance imaging conducted during
      hospitalisation revealed generalised cortical atrophy. The Paediatric Oncology
      department ruled out any association with tumours. Two years after onset of the
      clinical picture, with the patient free of convulsive seizures, a
      neuropsychological appraisal was carried out. Results showed involvement of the
      executive functions and a follow-up magnetic resonance scan revealed recovery
      from the cortical atrophy. CONCLUSIONS: The mechanism underlying reversible
      cortical atrophy is unknown but in patients with anti-NMDA receptor antibody
      encephalitis it could be directly proportional to the amount of antibodies in
      circulation and the length of time the cerebral cortex was exposed to them. An
      early diagnosis and initiating immunomodulation are essential.

PMID- 25952600
TI  - [Microdeletion 12p12 involving SOX5 gene: a new syndrome with developmental
      delay].
AB  - INTRODUCTION: The SOX5 gene encodes a transcription factor involved in the
      regulation of chondrogenesis and the development of the nervous system. CASE
      REPORT: We report a 10 years-old girl with developmental delay, behavior problems
      and dysmorphic features of this new syndrome with developmental delay. She had a
      12p12 deletion involving SOX5. CONCLUSIONS: We review the reported cases,
      intragenic SOX5 deletions and larger 12p12 deletions encompassing SOX5. We
      analyze the genotype-phenotype associations and the genes involved in our
      patient.

PMID- 25952601
TI  - Burning mouth syndrome: a review and update.
AB  - Burning mouth syndrome (BMS) is mainly found in middle aged or elderly women and
      is characterized by intense burning or itching sensation of the tongue or other
      regions of the oral mucosa. It can be accompanied by xerostomia and dysgeusia.
      The syndrome generally manifests spontaneously, and the discomfort is typically
      of a continuous nature but increases in intensity during the evening and at
      night. Although BMS classically has been attributed to a range of factors, in
      recent years evidence has been obtained relating it peripheral (sensory C and/or
      trigeminal nerve fibers) or central neuropathic disturbances (involving the
      nigrostriatal dopaminergic system). The differential diagnosis requires the
      exclusion of oral mucosal lesions or blood test alterations that can produce
      burning mouth sensation. Patient management is based on the avoidance of causes
      of oral irritation and the provision of psychological support. Drug treatment for
      burning sensation in primary BMS of peripheral origin can consist of topical
      clonazepam, while central type BMS appears to improve with the use of
      antidepressants such as duloxetine, antiseizure drugs such as gabapentin, or
      amisulpride. 

PMID- 25952602
TI  - [Therapeutic potential of bone marrow stem cells in cerebral infarction].
AB  - INTRODUCTION: Stem cells are an alternative therapy for cerebral infarction that
      is still in the experimental phase. AIMS: To report on the existing scientific
      evidence on the therapeutic potential of bone marrow stem cells in this disease.
      DEVELOPMENT: Cerebral infarction accounts for 80% of cerebrovascular diseases.
      Thrombolysis is the only approved therapy, but, owing to its narrow therapeutic
      window, it is only applied to a low percentage of patients. Conversely,
      neurorestorative treatments, such as stem cells, can be applied over longer
      periods of time. For this reason a literature search was conducted on PubMed
      using the key words 'stem cells', 'bone marrow derived mononuclear cells' and
      'stroke'. Evidence was found of the safety and effectiveness of such cells at
      different points in the development of the completed stroke. Results included
      studies that, in the clinical and preclinical period, collected them by spinal
      puncture and in peripheral blood, and transplanted them either directly into the
      infarcted area or intravenously. The therapeutic effect is related with their
      cell plasticity and trophic-factor releasing properties. CONCLUSIONS: Autologous
      mononuclear cell concentrate, obtained from peripheral blood or by puncturing the
      bone marrow and transplanted intravenously, is a feasible methodological option
      that will make it possible to quickly increase the number of clinical trials
      conducted at different stages of the development of a completed stroke. This
      therapy has proved itself to be safe and effective; nevertheless, further
      evidence is needed to endorse its generalised use in humans.

PMID- 25952603
TI  - [Carotidynia, back to an old controversial issue].

PMID- 25952604
TI  - [Venlafaxine-induced delirium mediated by high doses].

PMID- 25952605
TI  - [Paroxysmal atrial fibrillation within the context of cluster headaches].

PMID- 25952607
TI  - Liquid fat, a potential abiotic vector for horizontal transmission of salmonid
      alphavirus?
AB  - Viral diseases represent serious challenge in marine farming of Atlantic salmon
      (Salmo salar L). Pancreas disease (PD) caused by a salmonid alphavirus (SAV) is
      by far the most serious in northern Europe. To control PD, it is necessary to
      identify virus transmission routes. One aspect to consider is whether the virus
      is transported as free particles or associated with potential vectors. Farmed
      salmonids have high lipid content in their tissue which may be released into the
      environment from decomposing dead fish. At the seawater surface, the effects of
      wind and ocean currents are most prominent. The aim of this study was primarily
      to identify whether the lipid fraction leaking from dead infected salmon contains
      SAV. Adipose tissue from dead SAV-infected fish from three farming sites was
      submerged in beakers with sea water in the laboratory and stored at different
      temperature and time conditions. SAV was identified by real-time RT-PCR in the
      lipid fractions accumulating at the water surface in the beakers. SAV-RNA was
      also present in the sea water. Lipid fractions were transferred to cell culture,
      and viable SAV was identified. Due to its hydrophobic nature, fat with infective
      pathogenic virus at the surface may contribute to long-distance transmission of
      SAV. 

PMID- 25952608
TI  - Influence of fear of movement on total knee arthroplasty outcome.
AB  - arthroplasty (TKA) patients and to determine the association of fear of movement
      with established outcome measures. METHODS: A prospective study included 78
      patients with primary TKA for osteorthritis. The occurence of fear of movement
      was assessed by Tampa Scale of Kinesiophobia (TSK). The patients were assessed at
      three time points: 2 weeks, 4 weeks and 6 months after the surgery. Pain and
      flexion were measured at all the three time points while function according to
      the Oxford knee score 1 was evaluated only at 6 month after surgery. RESULTS:
      Fear of movement occurred in 17 patients (21.8%). Patients with a high degree of
      fear of movement showed significantly poorer results compared to those with a low
      degree in terms of pain, flexion and function. Improvement in pain and flexion
      over time was achieved in both groups but it was significantly greater in the low
      degree fear of movement group. DISCUSSION: Our study showed that postoperative
      fear of movement was significantly associated with pain, flexion and function.
      Other authors found that preoperative level of fear of movement was a predictor
      of postoperative functional limitations. CONCLUSIONS: Fear of movement occurred
      in a substantial proportion of patients after TKA and it was associated with knee
      pain, flexion and function. According to our results fear of movement may
      represent a risk for poor TKA outcome.

PMID- 25952610
TI  - Benefit-cost analysis of commercially available activated carbon filters for
      indoor ozone removal in single-family homes.
AB  - This study involved the development of a model for evaluating the potential costs
      and benefits of ozone control by activated carbon filtration in single-family
      homes. The modeling effort included the prediction of indoor ozone with and
      without activated carbon filtration in the HVAC system. As one application, the
      model was used to predict benefit-to-cost ratios for single-family homes in 12
      American cities in five different climate zones. Health benefits were evaluated
      using disability-adjusted life-years and included city-specific age demographics
      for each simulation. Costs of commercially available activated carbon filters
      included capital cost differences when compared to conventional HVAC filters of
      similar particle removal efficiency, energy penalties due to additional pressure
      drop, and regional utility rates. The average indoor ozone removal effectiveness
      ranged from 4 to 20% across the 12 target cities and was largely limited by HVAC
      system operation time. For the parameters selected in this study, the mean
      predicted benefit-to-cost ratios for 1-inch filters were >1.0 in 10 of the 12
      cities. The benefits of residential activated carbon filters were greatest in
      cities with high seasonal ozone and HVAC usage, suggesting the importance of
      targeting such conditions for activated carbon filter applications.

PMID- 25952609
TI  - Heterozygous genome assembly via binary classification of homologous sequence.
AB  - BACKGROUND: Genome assemblers to date have predominantly targeted haploid
      reference reconstruction from homozygous data. When applied to diploid genome
      assembly, these assemblers perform poorly, owing to the violation of assumptions
      during both the contigging and scaffolding phases. Effective tools to overcome
      these problems are in growing demand. Increasing parameter stringency during
      contigging is an effective solution to obtaining haplotype-specific contigs;
      however, effective algorithms for scaffolding such contigs are lacking. METHODS:
      We present a stand-alone scaffolding algorithm, ScaffoldScaffolder, designed
      specifically for scaffolding diploid genomes. The algorithm identifies homologous
      sequences as found in "bubble" structures in scaffold graphs. Machine learning
      classification is used to then classify sequences in partial bubbles as
      homologous or non-homologous sequences prior to reconstructing haplotype-specific
      scaffolds. We define four new metrics for assessing diploid scaffolding accuracy:
      contig sequencing depth, contig homogeneity, phase group homogeneity, and
      heterogeneity between phase groups. RESULTS: We demonstrate the viability of
      using bubbles to identify heterozygous homologous contigs, which we term
      homolotigs. We show that machine learning classification trained on these
      homolotig pairs can be used effectively for identifying homologous sequences
      elsewhere in the data with high precision (assuming error-free reads).
      CONCLUSION: More work is required to comparatively analyze this approach on real
      data with various parameters and classifiers against other diploid genome
      assembly methods. However, the initial results of ScaffoldScaffolder supply
      validity to the idea of employing machine learning in the difficult task of
      diploid genome assembly. Software is available at
      http://bioresearch.byu.edu/scaffoldscaffolder.

PMID- 25952611
TI  - Determination of solute site occupancies within gamma' precipitates in nickel
      base superalloys via orientation-specific atom probe tomography.
AB  - The analytical limitations in atom probe tomography such as resolving a desired
      set of atomic planes, for solving complex materials science problems, have been
      overcome by employing a well-developed unique and reproducible crystallographic
      technique, involving synergetic coupling of orientation microscopy with atom
      probe tomography. The crystallographic information in atom probe reconstructions
      has been utilized to determine the solute site occupancies in Ni-Al-Cr based
      superalloys accurately. The structural information in atom probe reveals that
      both Al and Cr occupy the same sub-lattice within the L12-ordered gamma'
      precipitates to form Ni3(Al,Cr) precipitates in a Ni-14Al-7Cr (at%) alloy.
      Interestingly, the addition of Co, which is a solid solution strengthener, to a
      Ni-14Al-7Cr alloy results in the partial reversal of Al site occupancy within
      gamma' precipitates to form (Ni,Al)3(Al,Cr,Co) precipitates. This unique evidence
      of reversal of Al site occupancy, resulting from the introduction of other
      solutes within the ordered structures, gives insights into the relative
      energetics of different sub-lattice sites when occupied by different solutes. 

PMID- 25952612
TI  - Dimer-on-mirror SERS substrates with attogram sensitivity fabricated by colloidal
      lithography.
AB  - Nanoplasmonic substrates with optimized field-enhancement properties are a key
      component in the continued development of surface-enhanced Raman scattering
      (SERS) molecular analysis but are challenging to produce inexpensively in large
      scale. We used a facile and cost-effective bottom-up technique, colloidal hole
      mask lithography, to produce macroscopic dimer-on-mirror gold nanostructures. The
      optimized structures exhibit excellent SERS performance, as exemplified by
      detection of 2.5 and 50 attograms of BPE, a common SERS probe, using Raman
      microscopy and a simple handheld device, respectively. The corresponding Raman
      enhancement factor is of the order 10(11), which compares favourably to
      previously reported record performance values. 

PMID- 25952613
TI  - Why the distribution of medical errors matters.
AB  - During the last decade, interventions to reduce the number of medical errors have
      been largely ineffective. Although it is widely assumed that medical errors
      follow a Gaussian distribution, they may actually follow a Power Rule
      distribution. This article presents the evidence in favor of a Power Rule
      distribution for medical errors and then examines the consequences of such a
      distribution for medical errors. As the distribution of medical errors has real
      world implications, further research is needed to determine whether medical
      errors follow a Gaussian or Power Rule distribution. 

PMID- 25952614
TI  - Effectiveness and safety of laparoscopic adrenalectomy of large pheochromocytoma:
      a prospective, nonrandomized, controlled study.
AB  - BACKGROUND: Laparoscopic adrenalectomy (LA) is normally used to treat small-sized
      (<6 cm) pheochromocytoma (PCC). This study evaluated the effectiveness and safety
      of LA for treating large (>=6 cm) PCC. METHODS: Fifty-one patients with
      resectable, large-sized (>=6 cm) PCC were prospectively enrolled for elective LA
      (n = 23) or open adrenalectomy (n = 28). RESULTS: LA was converted into open
      adrenalectomy in 2 patients (2/23, 8.7%); LA was associated with relatively
      longer operative time (P = .033) but less intraoperative bleeding (P < .001),
      faster resumption of ambulatory status (P < .001), and shorter duration of
      postoperative hospitalization (P < .001). Frequency of PCC recurrence was similar
      between the 2 groups (P = 1.000). CONCLUSIONS: LA is a feasible, effective, and
      safe treatment modality for large-sized (>=6 cm) PCC. LA is associated with
      minimal invasiveness and faster postoperative recovery.

PMID- 25952615
TI  - Moroccan study of HLA (-A, -B, -C, -DR, -DQ) polymorphism in 647 unrelated
      controls: Updating data.
AB  - The scope of this study is to investigate the HLA (Human Leukocyte Antigen)
      distribution and polymorphism in a large sample of healthy Moroccans in order to
      extend and update the available data. 647 unrelated Moroccan controls originating
      from diverse regions of the country were typed using microlymphocytotoxicity for
      HLA-A and -B, sequence-specific-primer amplification for -C, -DR, and -DQ and
      Luminex HD for specific -DR. The most frequent allele groups detected were HLA-A2
      (19.2%), -B44 (12.4%), -C*07 (24.4%), -DRB1*03 (16.9%), -DRB1*04 (18.4%), 
      DQB1*02 (28.7%) and -DQB1*03 (27.8%). The most predominant specific alleles found
      for DRB1 were: *03:01, *04:02, *04:05, *07:01, *11:01, *13:02 and *15:01. Rare
      allelic variants were detected, for the first time in Moroccan population, at the
      DRB1*03 (*03:52, *03:54, *03:56), DRB1*07 (*07:07, *07:11, *07:16) and DRB1*11
      (*11:70) locus. The most frequent haplotypes were: A2-B44, A30-B18, A2-C*16, A30
      C*06, B14-C*08, B58-C*07, B45-C*06, DRB1*03-DQB1*02, DRB1*04-DQB1*03, DRB1*07
      DQB1*02 and DRB1*15-DQB1*06. Comparison of genetic distances and haplotypes with
      other populations shows that the Moroccans are genetically closer to North
      Africans and Europeans than to sub-Saharan Africans. Our results reflect the high
      degree of HLA polymorphism in the Moroccan population and provide a useful
      baseline of healthy Moroccan controls for disease association and anthropological
      studies. 

PMID- 25952616
TI  - Journal club: Multicenter study of health care costs of patients admitted to
      hospital with Staphylococcus aureus bacteremia: Impact of length of stay and
      intensity of care.

PMID- 25952617
TI  - Comparing visual inspection, aerobic colony counts, and adenosine triphosphate
      bioluminescence assay for evaluating surface cleanliness at a medical center.
AB  - BACKGROUND: Environmental cleaning is essential in reducing microbial
      colonization and health care-associated infections in hospitals. However, there
      is no consensus for the standard method to assess hospital cleanliness, and
      comparisons of newer methodology, such as adenosine triphosphate bioluminescence
      assay, with the traditional methods are limited. METHODS: A prospective study was
      conducted at a medical center between January 2013 and August 2013. In each
      selected room, 10-12 high-touch surfaces were sampled before and after terminal
      cleaning. The adequacy of cleaning was evaluated by visual inspection, aerobic
      colony counts (ACCs), and adenosine triphosphate (ATP) bioluminescence assay.
      RESULTS: Eighty-five environmental surfaces from 8 rooms were evaluated by all 3
      methods. The overall inadequacy defined by visual inspection, ACC, and ATP level
      was 11.8%, 20.0%, and 50.6% before cleaning and 4.7%, 5.9%, 21.2% after cleaning,
      respectively. A correlation between the ACC and ATP was found (r = 0.285, P <
      .001) using log10 values. Using ACCs <2.5 colony forming units/cm(2) as the
      cutoff for cleanliness, the ATP assay had better sensitivity than visual
      inspection (63.6% vs 27.3%). The receiver operating characteristics of the ATP
      assay indicated that the optimal ATP cutoff value was estimated to be 5.57
      relative light units/cm(2). CONCLUSION: ATP bioluminescence assay is a sensitive
      and rapid tool in evaluating the quality of terminal cleaning. We emphasize the
      value of using a quantitative method to monitor environmental cleaning at
      hospitals.

PMID- 25952619
TI  - Lasting hand self-disinfection: A backup for hospital hand hygiene?
AB  - BACKGROUND: Hand disinfection should be performed on the occasion of 5 separate
      moments during patient care, but some occasions are skipped. Can using hand
      antiseptics with residual effect reduce the problem of infection spread? We
      evaluated a 30-minute residual effect by different antiseptic products on
      endogenous and acquired microbiota. METHODS: The products tested were 2% and 5%
      chlorhexidine, 1% and 10% iodine povidone, 60 degrees  n-propanol, 0.2%
      mecetronium + isopropanol, and 0.6% chlorhexidine + isopropanol + 0.1%
      benzalconium chloride. The microorganisms identified were 3 ATCC and 9
      multiresistant strains isolated from intensive care unit patients (used as
      acquired microbiota). Logarithmic (log10) reductions of the colony forming units
      obtained with each antiseptic product and for each microorganism were calculated
      via in vivo (6 volunteers) and in vitro tests. RESULTS: The better in vivo and in
      vitro products with a residual effect > 2 log10 after 30 minutes on hands were 2%
      5% chlorhexidine and 0.6% chlorhexidine + isopropanol + 0.1% benzalconium
      chloride. This reduction was significantly different (P < .01) from the other 4
      antiseptics. This residual effect (> 2 log10) can be considered a self
      disinfecting hand status in daily practice. CONCLUSIONS: Hand antiseptics used in
      hospitals must pass tests of residual efficacy (after 30 minutes on acquired
      microbiota) showing a reduction > 2 log10 in vivo and in vitro. A good product
      can be the mixture of chlorhexidine + alcohol + benzalconium chloride.

PMID- 25952618
TI  - Challenges in assessing transmission of Mycobacterium tuberculosis in long-term
      care facilities.

PMID- 25952620
TI  - Portal vein recanalization and embolization of the transsplenic puncture tract
      using an Amplatzer(r) vascular plug: a case report.
AB  - BACKGROUND: A transsplenic access for the catheterization of the portal venous
      system to treat a portal vein thrombosis and/or stenosis entails the risk of
      intra-abdominal or intrasplenic bleeding complications and has to be seen as an
      approach of last resort. This is one of few reported cases in the literature
      where a transsplenic puncture tract was successfully embolized using an
      Amplatzer(r) vascular plug 4 (8 mm; St. Jude Medical). CASE PRESENTATION: This is
      the case report of a 58 years old Caucasian male patient who had received right
      sided extended hemihepatectomy with partial resection of the portal vein due to
      hilar cholangiocarcinoma three years ago. The patient suffered from portal
      hypertension with difficult controllable bleeding of esophageal varices due to
      chronically progressive thrombosis of the portal vein caused by chronic
      anastomosis stenosis of the reconstructed left portal vein branch (confirmed in a
      Magnetic Resonance Imaging (MRI) examination 6 months after the portal vein
      reconstruction). A transsplenic access (6 French) was chosen to allow
      recanalization of the portal vein, stent-angioplasty of the anastomosis and
      coiling of the gastric varices. The transsplenic tract was successfully embolized
      with an Amplatzer(r) Vascular Plug 4 and gelfoam pledgets. CONCLUSION:
      Amplatzer(r) Vascular plugs in combination with gelatin sponges can be used to
      efficiently and precisely seal transsplenic puncture sites.

PMID- 25952621
TI  - Utilization of a Meldrum's acid towards functionalized fluoropolymers possessing
      dual reactivity for thermal crosslinking and post-polymerization modification.
AB  - New thermally cross-linkable and/or post-functionalizable perfluorocyclobutyl
      (PFCB) polymers containing Meldrum's acid moieties have been successfully
      prepared via the thermal cyclopolymerization of a new Meldrum's acid
      functionalized aromatic trifluorovinyl ether (TFVE) monomer. 

PMID- 25952622
TI  - The endoderm and myocardium join forces to drive early heart tube assembly.
AB  - Formation of the muscular layer of the heart, the myocardium, involves the medial
      movement of bilateral progenitor fields; driven primarily by shortening of the
      endoderm during foregut formation. Using a combination of time-lapse imaging,
      microsurgical perturbations and computational modeling, we show that the speed of
      the medial-ward movement of the myocardial progenitors is similar, but not
      identical to that of the adjacent endoderm. Further, the extracellular matrix
      microenvironment separating the two germ layers also moves with the myocardium,
      indicating that collective tissue motion and not cell migration drives tubular
      heart assembly. Importantly, as myocardial cells approach the midline, they
      perform distinct anterior-directed movements relative to the endoderm. Based on
      the analysis of microincision experiments and computational models, we propose
      two characteristic, autonomous morphogenetic activities within the early
      myocardium: 1) an active contraction of the medial portion of the heart field and
      2) curling- the tendency of the unconstrained myocardial tissue to form a
      spherical surface with a concave ventral side. In the intact embryo, these
      deformations are constrained by the endoderm and the adjacent mesoderm,
      nevertheless the corresponding mechanical stresses contribute to the proper
      positioning of myocardial primordia. 

PMID- 25952623
TI  - Force field-dependent solution properties of glycine oligomers.
AB  - Molecular simulations can be used to study disordered polypeptide systems and to
      generate hypotheses on the underlying structural and thermodynamic mechanisms
      that govern their function. As the number of disordered protein systems
      investigated with simulations increase, it is important to understand how
      particular force fields affect the structural properties of disordered
      polypeptides in solution. To this end, we performed a comparative structural
      analysis of Gly(3) and Gly(10) in aqueous solution from all atom, microsecond
      molecular dynamics (MD) simulations using the CHARMM 27 (C27), CHARMM 36 (C36),
      and Amber ff12SB force fields. For each force field, Gly(3) and Gly(10) were
      simulated for at least 300 ns and 1 MUs, respectively. Simulating oligoglycines
      of two different lengths allows us to evaluate how force field effects depend on
      polypeptide length. Using a variety of structural metrics (e.g., end-to-end
      distance, radius of gyration, dihedral angle distributions), we characterize the
      distribution of oligoglycine conformers for each force field and show that each
      sample conformation space differently, yielding considerably different structural
      tendencies of the same oligoglycine model in solution. Notably, we find that C36
      samples more extended oligoglycine structures than both C27 and ff12SB.

PMID- 25952624
TI  - Suppressive oligodeoxynucleotides induced tolerogenic plasmacytoid dendritic
      cells and ameliorated the experimental autoimmune neuritis.
AB  - Toll-like receptor (TLR) 9, recognizing different ligands, confers distinct
      features of plasmacytoid dendritic cells (pDCs). Our previous study demonstrated
      a role for TLR9 in the mechanism of experimental autoimmune neuritis (EAN). In
      this study, we explored whether suppressive oligodeoxynucleotides (sODN) could
      induce tolerogenic pDCs via TLR9 and thus promote the recovery of EAN. Effects of
      different TLR9 ligands, CpG ODN and sODN on P0 180-199 peptide-stimulated pDCs
      were measured by detecting the expression of co-stimulatory molecules,
      indoleamine 2,3-dioxygenase (IDO), secretion of Th1- and Th2-type cytokines and
      the TLR9 signaling pathway. CpG ODN- or sODN-treated pDCs were intravenously
      injected into the EAN mice and their effects were compared. Our data showed that
      P0180-199 peptides significantly promoted mRNA expression of co-stimulatory
      molecules (CD40, CD80 and CD86) in pDCs and induced secretion of Th1-type
      cytokines. Treatment of CpG ODN aggravated the effects of P0 180-199 peptides on
      pDCs; however, sODN had the opposite effects and significantly upregulated the
      IDO expression in pDCs. Further analysis showed that MYD88 is necessary for sODN
      to modulate the TLR9/NF-kappaB signaling in pDCs. Finally, the sODN-treated pDCs
      significantly promoted recovery of the EAN mice. Taken together, sODN could
      induce tolerogenic pDCs and thus ameliorate the EAN.

PMID- 25952627
TI  - The importance of vaccination and immunoglobulin treatment for patients with
      primary immunodeficiency diseases (PIDs)--World PI Week April 22-29, 2015.

PMID- 25952632
TI  - Anti-senescence effects of DNA methyltransferase inhibitor RG108 in human bone
      marrow mesenchymal stromal cells.
AB  - Alteration of DNA methylation is highly associated with ageing and ageing-related
      diseases. Remedy of the altered methylation pattern may provide beneficial
      efficacy in these diseases. In this study, we used a DNA methyltransferase
      inhibitor, RG108, to investigate the senescence effects in human bone marrow
      mesenchymal stromal cells (hBM-MSCs). First, we determined the optimized dose and
      time of RG108 treatment in hBM-MSCs to be 5 uM for 48 H, respectively. Under
      these conditions, the anti-senescence genes TERT, bFGF, VEGF, and ANG were
      increased, whereas the senescence-related genes ATM, p21, and p53 were decreased.
      The number of beta-galactosidase-positive cells was significantly decreased in
      RG108-treated MSCs, whereas the rates of MSC migration and cellular protection
      were increased. We have shown that RG108 significantly induces the expression of
      TERT by blocking methylation at the TERT promoter region. Thus, these data
      indicate that an optimized dose of RG108 may improve the cell migration,
      protection, cellular senescence, which may provide a better efficacy of these
      cells in stem cell therapy. 

PMID- 25952633
TI  - Household practices related to disease transmission between animals and humans in
      rural Cambodia.
AB  - BACKGROUND: Zoonotic diseases are disproportionately affecting poor societies in
      low-income countries and pose a growing threat to public health and global food
      security. Rural Cambodian households may face an increased likelihood of exposure
      to zoonotic diseases as people there live in close association with livestock.
      The objectives of the study was to identify practices known to influence zoonosis
      transmission in rural Cambodian households and relate the practices to agro
      ecological region, socio-economic position, demographics, livestock management
      and zoonosis awareness. METHODS: The study was conducted in three different agro
      ecological regions of Cambodia; 10 villages each in the central lowlands, north
      west wetlands and on the south coast, where information was obtained in
      questionnaires administered to 300 households, and 30 village heads and animal
      health workers. RESULTS: Descriptive analysis revealed a gender difference in
      responsibility for livestock and that the main purpose of raising livestock was
      for sale. Few respondents (6%) perceived a likelihood of disease transmission in
      their village between livestock, humans and wildlife, despite household practices
      related to zoonosis transmission being common. More than one-forth of households
      practised behaviours such as culling sick animals for consumption, eating animals
      found dead and allowing animals to enter sleeping and food preparation areas.
      Associations between household practices and possible explanatory factors were
      analysed with multivariable models using generalised estimation equations to
      account for clustering of practices within villages. Factors found to influence
      household practices were agro-ecological region, socio-economic position, number
      of people in the household, livestock species reared and awareness of zoonoses.
      CONCLUSIONS: Cambodia has experienced numerous fatal human cases of zoonotic
      influenza and extensive influenza information campaigns have been run, yet only a
      few of the households surveyed here reported the threat of zoonosis to be a
      concern in their village. Zoonosis awareness was positively related to hand
      washing behaviour, but other practices associated with an increased or decreased
      likelihood of exposure to zoonotic pathogens were unaffected by awareness. The
      findings indicate a knowledge-to-action gap among rural farmers and highlight the
      necessity for reconstructed interventions in zoonotic disease control.

PMID- 25952635
TI  - Pharmacotherapy for eosinophilic esophagitis.

PMID- 25952634
TI  - Glargine insulin/gliclazide MR combination therapy is more effective than
      premixed insulin monotherapy in Chinese patients with type 2 diabetes
      inadequately controlled on oral antidiabetic drugs.
AB  - BACKGROUND: The aim of this study is to compare the efficacy and safety of once
      daily insulin glargine plus gliclazide modified release combination therapy
      versus twice-daily premixed insulin monotherapy in Chinese type 2 diabetic
      patients insufficiently controlled by oral antidiabetic agents. METHODS: In a 12
      week, multicenter, randomized, parallel-group clinical trial, patients with poor
      glycaemic control (fasting plasma glucose >= 7.0 mmol/L and 7.5% < haemoglobin
      A1c  <= 10%) on oral antidiabetic drugs were randomized to the treatment groups
      for combination therapy (n = 52) or monotherapy (n = 53). Continuous glucose
      monitoring was carried out over two 72-h periods, at the beginning and the end of
      the study, and the data were used to calculate the 24-h mean blood glucose, mean
      amplitude of glycaemic excursions, standard deviation of blood glucose, and the
      mean of daily differences. RESULTS: The mean haemoglobin A1c decrease from
      baseline to study end was significant for both treatment groups (combination
      therapy: -1.23 +/- 0.92%; insulin monotherapy: -1.02 +/- 1.04%); moreover, the
      combination therapy group showed a significantly more robust haemoglobin A1c
      decrease (p = 0.0308). Both therapies significantly reduced the 24-h mean blood
      glucose (both, p < 0.001), but neither produced a significant effect on glycaemic
      variability, calculated as mean amplitude of glycaemic excursions, standard
      deviation of blood glucose, and mean of daily differences. In addition, the
      effects on rates of hypoglycaemic episodes were similar between the two
      therapies. CONCLUSIONS: Chinese patients with type 2 diabetes inadequately
      controlled with oral antidiabetic agents attained greater benefit from once-daily
      insulin glargine plus gliclazide modified release regimen than from a twice-daily
      premixed insulin regimen.

PMID- 25952636
TI  - Hymenoptera venom immunotherapy while maintaining cardiovascular medication: safe
      and effective.
AB  - BACKGROUND: The hypothetical risks of cardiovascular medication during
      Hymenoptera venom immunotherapy (VIT) are still a matter of controversy.
      OBJECTIVE: To assess the potential influence of beta-blockers (BBs) and/or
      angiotensin-converting enzyme inhibitors (ACEIs) on the long-term safety and
      outcome of VIT. METHODS: Data on the course of VIT maintenance phase, Hymenoptera
      re-stings, and concurrent medication were retrospectively derived from
      standardized questionnaires in a cohort of patients with significant
      cardiovascular comorbidity. RESULTS: Of 225 patients, 125 (55.6%) were taking
      cardiovascular medication at the time of data collection: 71 (31.6%) took an
      ACEI, and 40 (17.8%) took a BB. A total of 3,397 months of maintenance VIT during
      intake of an ACEI and 1,418 months during BB therapy were evaluated. Cumulative
      VIT-related reaction rates, including subjective symptoms, were 9.1% per
      treatment cycle and 0.31% per injection, with objective reaction rates of 1.7%
      and 0.06%, respectively. The incidence of adverse events was significantly higher
      in patients with a previous history of systemic reactions at VIT buildup (P =
      .004). Surprisingly, reaction rates were lower in patients taking any kind of
      cardiovascular medication (P = .04) or an ACEI (P = .03). The overall reexposure
      rate to Hymenoptera stings was 42.7%, and the field sting-induced objective
      reaction rate was 7.3%. There was no evidence of an increase of field sting
      related relapse or hospitalization rates by concurrent cardiovascular medication.
      CONCLUSION: Cardiovascular medication does not impair the safety and/or the
      efficacy of Hymenoptera VIT.

PMID- 25952637
TI  - Cloud-computing and smartphones: tools for improving asthma management and
      understanding environmental triggers.

PMID- 25952638
TI  - Author response.

PMID- 25952639
TI  - Role of IgA and IgM in severity of atopic dermatitis.

PMID- 25952640
TI  - Allergen of the month--white bursage.

PMID- 25952641
TI  - Safety and efficacy compared between irinotecan-loaded microspheres HepaSphere
      and DC bead in a model of VX2 liver metastases in the rabbit.
AB  - PURPOSE: To compare irinotecan-eluting HepaSphere (BioSphere Medical, Roissy-en
      France, France) and DC Bead (Biocompatibles UK Ltd, London, United Kingdom)
      embolization microspheres for distribution in tumors, release properties,
      tolerance, and antitumor effects in a model of liver metastases in the rabbit.
      MATERIALS AND METHODS: Multiple liver tumors were created by injection of a VX2
      cell suspension in the portal vein of rabbits. After 2 weeks, embolization of the
      proper hepatic artery was performed with a fixed volume of bland HepaSphere (n =
      5), irinotecan-loaded HepaSphere (n = 6), or irinotecan-loaded DC Bead (n = 5)
      microspheres. Untreated animals injected with VX2 cells served as control animals
      (n = 5). Plasma pharmacokinetics of irinotecan and its metabolite SN38 were
      assessed. Histopathology and gene expression analysis were performed 3 days after
      treatment. RESULTS: Among all treated groups, there was no significant difference
      in liver enzymes or liver damage on histology. Irinotecan-loaded HepaSphere
      microspheres showed a faster release of drug than DC Bead microspheres leading to
      a twofold higher concentration of drug in plasma for HepaSphere microspheres.
      HepaSphere microspheres were less frequently found inside tumor nodules on
      histology than DC Bead microspheres (11% vs 48%, P < .001) because of their
      larger size. Tumor necrosis was significantly greater for rabbits given
      irinotecan-loaded HepaSphere microspheres (69% of total tumor surface) and
      rabbits given DC Bead microspheres (50% of total tumor surface) compared with
      control animals (24% of total tumor surface, P = .006 and P = .047). CONCLUSIONS:
      HepaSphere and DC Bead microspheres loaded with irinotecan caused significant
      necrosis of tumor nodules in a model of VX2 liver metastases. This outcome was
      mostly due to irinotecan delivery rather than vascular occlusion by the
      microspheres and was greater for HepaSphere microspheres compared with DC Bead
      microspheres.

PMID- 25952643
TI  - Electric conductive pattern element fabricated using commercial inkjet printer
      for paper-based analytical devices.
AB  - Herein, we proposed the addition of an inkjet-printed conductive pattern to paper
      based analytical devices (PADs) in order to expand their applications. An
      electric conductive pattern was easily, quickly, and inexpensively fabricated
      using a commercial inkjet printer. The addition of a printed electric element
      will enhance the applications of PADs without the loss of properties such as cost
      efficiency, disposability, and portability. In this study, we applied an inkjet
      printed heater to a piece of paper and investigated its characteristics. The use
      of the heater as a valve, concentrator, and heat source for chemical reactions on
      PADs was investigated. Previously, these functions were difficult to realize with
      PADs. The inkjet-printed heater was used as a valve and concentrator through
      evaporation of the working fluid and solvent, and was also found to be useful for
      providing heat for chemical reactions. Thus, the combination of printed electric
      circuits and PADs has many potential applications. 

PMID- 25952642
TI  - Hemodynamic and Hematologic Effects of Histotripsy of Free-Flowing Blood:
      Implications for Ultrasound-Mediated Thrombolysis.
AB  - PURPOSE: To investigate the extent and consequences of histotripsy-induced
      hemolysis in vivo. MATERIALS AND METHODS: Porcine femoral venous blood was
      treated with histotripsy in 11 animals with systemic heparinization and 11
      without heparin. Serum and hemodynamic measurements were obtained at 0, 2, 5, 10,
      15, and 30 minutes and 48-72 hours after the procedure. Fisher exact test was
      used to determine differences in mortality between heparinized and nonheparinized
      groups. A linear mixed effects model was used to test for differences in blood
      analytes and hemodynamic variables over time. RESULTS: Of 11 animals in the
      nonheparinized group, 5 died during or immediately after histotripsy (45%
      nonheparin mortality vs 0% heparin mortality, P = .035). Serum hematocrit, free
      hemoglobin, lactate dehydrogenase (LDH), and right ventricular systolic pressure
      changed significantly (P < .001) over the treatment time. Serum hematocrit
      decreased slightly (from 32.5% +/- 3.6% to 29.4% +/- 4.2%), whereas increases
      were seen in free hemoglobin (from 6.2 mg/dL +/- 4.6 to 348 mg/dL +/- 100), LDH
      (from 365 U/L +/- 67.8 +/- to 722 U/L +/- 84.7), and right ventricular systolic
      pressure (from 23.2 mm Hg +/- 7.2 to 39.7 mm Hg +/- 12.3). After 48-72 hours,
      hematocrit remained slightly decreased (P = .005), whereas LDH and free
      hemoglobin remained slightly increased compared with baseline (both P < .001).
      CONCLUSIONS: Intravascular histotripsy applied to free-flowing venous blood is
      safe with systemic heparinization, causing only transient hemodynamic and
      metabolic disturbances, supporting its use as a future noninvasive thrombolytic
      therapy modality.

PMID- 25952644
TI  - Validity of the Medical College Admission Test for predicting MD-PhD student
      outcomes.
AB  - The Medical College Admission Test (MCAT) is a quantitative metric used by MD and
      MD-PhD programs to evaluate applicants for admission. This study assessed the
      validity of the MCAT in predicting training performance measures and career
      outcomes for MD-PhD students at a single institution. The study population
      consisted of 153 graduates of the Vanderbilt Medical Scientist Training Program
      (combined MD-PhD program) who matriculated between 1963 and 2003 and completed
      dual-degree training. This population was divided into three cohorts
      corresponding to the version of the MCAT taken at the time of application.
      Multivariable regression (logistic for binary outcomes and linear for continuous
      outcomes) was used to analyze factors associated with outcome measures. The MCAT
      score and undergraduate GPA (uGPA) were treated as independent variables; medical
      and graduate school grades, time-to-PhD defense, USMLE scores, publication
      number, and career outcome were dependent variables. For cohort 1 (1963-1977),
      MCAT score was not associated with any assessed outcome, although uGPA was
      associated with medical school preclinical GPA and graduate school GPA (gsGPA).
      For cohort 2 (1978-1991), MCAT score was associated with USMLE Step II score and
      inversely correlated with publication number, and uGPA was associated with
      preclinical GPA (mspGPA) and clinical GPA (mscGPA). For cohort 3 (1992-2003), the
      MCAT score was associated with mscGPA, and uGPA was associated with gsGPA.
      Overall, MCAT score and uGPA were inconsistent or weak predictors of training
      metrics and career outcomes for this population of MD-PhD students. 

PMID- 25952645
TI  - Students' reflections on the relationships between safe learning environments,
      learning challenge and positive experiences of learning in a simulated GP clinic.
AB  - Learning environments are a significant determinant of student behaviour,
      achievement and satisfaction. In this article we use students' reflective essays
      to identify key features of the learning environment that contributed to positive
      and transformative learning experiences. We explore the relationships between
      these features, the students' sense of safety in the learning environment (LE),
      the resulting learning challenge with which they could cope and their positive
      reports of the experience itself. Our students worked in a unique simulation of
      General Practice, the Safe and Effective Clinical Outcomes clinic, where they
      consistently reported positive experiences of learning. We analysed 77 essays
      from 2011 and 2012 using an immersion/crystallisation framework. Half of the
      students referred to the safety of the learning environment spontaneously.
      Students described deep learning experiences in their simulated consultations.
      Students valued features of the LE which contributed to a psychologically safe
      environment. Together with the provision of constructive support and immediate,
      individualised feedback this feeling of safety assisted students to find their
      own way through clinical dilemmas. These factors combine to make students feel
      relaxed and able to take on challenges that otherwise would have been
      overwhelming. Errors became learning opportunities and students could practice
      purposefully. We draw on literature from medical education, educational
      psychology and sociology to interpret our findings. Our results demonstrate
      relationships between safe learning environments, learning challenge and powerful
      learning experiences, justifying close attention to the construction of learning
      environments to promote student learning, confidence and motivation. 

PMID- 25952646
TI  - Characteristic features of cognitive, affective and daily living functions of
      late-elderly dementia.
AB  - AIMS: The world is rapidly aging, and is facing an increase of late-elderly
      dementia patients. It is important to investigate the characteristic features of
      late-elderly dementia in a super-aged country. METHODS: We examined 1554 patients
      with cognitive decline in Department of Neurology, Okayama University Hospital,
      Okayama, Japan, divided into three subgroups according to the age: young-elderly
      (age <=64 years), middle-elderly (age 65-74 years) and late-elderly (age 75
      years), and investigated the cognitive, affective and activities of daily living
      functions (ADL), especially in late-elderly patients compared with young-elderly
      and middle-elderly patients. RESULTS: Among 1554 patients, Alzheimer's disease
      dominated at 62%, and age-dependently increased up to 69% in the late-elderly
      group. The total scores of four cognitive tests were significantly worse with
      aging for specific subscales of orientation, recall, visual retention, word
      fluency and so on. In contrast, total scores of the affective tests showed only
      an increase in the apathy scale in the late-elderly group. Each subgroup showed
      depressive/depression in 63.2-55.2%, and apathy in 44.2-54.8%. Furthermore,
      instrumental ADL items significantly deteriorated in the late-elderly group,
      which statistically correlated with Mini-Mental State Examination score.
      CONCLUSIONS: These results show that the late-elderly group is characterized by
      significant cognitive declines, increasing apathy, and instrumental ADL decrease.
      The cognitive decline may be related to such affective and ADL declines.

PMID- 25952647
TI  - Chemotherapy-Derived Inflammatory Responses Accelerate the Formation of
      Immunosuppressive Myeloid Cells in the Tissue Microenvironment of Human
      Pancreatic Cancer.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic
      malignancies. PDAC builds a tumor microenvironment that plays critical roles in
      tumor progression and metastasis. However, the relationship between chemotherapy
      and modulation of PDAC-induced tumor microenvironment remains poorly understood.
      In this study, we report a role of chemotherapy-derived inflammatory response in
      the enrichment of PDAC microenvironment with immunosuppressive myeloid cells.
      Granulocyte macrophage colony-stimulating factor (GM-CSF) is a major cytokine
      associated with oncogenic KRAS in PDAC cells. GM-CSF production was significantly
      enhanced in various PDAC cell lines or PDAC tumor tissues from patients after
      treatment with chemotherapy, which induced the differentiation of monocytes into
      myeloid-derived suppressor cells (MDSC). Furthermore, blockade of GM-CSF with
      monoclonal antibodies helped to restore T-cell proliferation when cocultured with
      monocytes stimulated with tumor supernatants. GM-CSF expression was also observed
      in primary tumors and correlated with poor prognosis in PDAC patients. Together,
      these results describe a role of GM-CSF in the modification of chemotherapy
      treated PDAC microenvironment and suggest that the targeting of GM-CSF may
      benefit PDAC patients' refractory to current anticancer regimens by defeating
      MDSC-mediated immune escape.

PMID- 25952648
TI  - Paracrine Effect of NRG1 and HGF Drives Resistance to MEK Inhibitors in
      Metastatic Uveal Melanoma.
AB  - Uveal melanoma patients with metastatic disease usually die within one year,
      emphasizing an urgent need to develop new treatment strategies for this cancer.
      MEK inhibitors improve survival in cutaneous melanoma patients but show only
      modest efficacy in metastatic uveal melanoma patients. In this study, we screened
      for growth factors that elicited resistance in newly characterized metastatic
      uveal melanoma cell lines to clinical-grade MEK inhibitors, trametinib and
      selumetinib. We show that neuregulin 1 (NRG1) and hepatocyte growth factor (HGF)
      provide resistance to MEK inhibition. Mechanistically, trametinib enhances the
      responsiveness to NRG1 and sustained HGF-mediated activation of AKT. Individually
      targeting ERBB3 and cMET, the receptors for NRG1 and HGF, respectively, overcome
      resistance to trametinib provided by these growth factors and by conditioned
      medium from fibroblasts that produce NRG1 and HGF. Inhibition of AKT also
      effectively reverses the protective effect of NRG1 and HGF in trametinib-treated
      cells. Uveal melanoma xenografts growing in the liver in vivo and a subset of
      liver metastases of uveal melanoma patients express activated forms of ERBB2 (the
      coreceptor for ERBB3) and cMET. Together, these results provide preclinical
      evidence for the use of MEK inhibitors in combination with clinical-grade anti
      ERBB3 or anti-cMET monoclonal antibodies in metastatic uveal melanoma.

PMID- 25952649
TI  - Hepatocellular Shuttling and Recirculation of Sorafenib-Glucuronide Is Dependent
      on Abcc2, Abcc3, and Oatp1a/1b.
AB  - Recently, an efficient liver detoxification process dubbed "hepatocyte hopping"
      was proposed on the basis of findings with the endogenous compound, bilirubin
      glucuronide. According to this model, hepatocytic bilirubin glucuronide can
      follow a liver-to-blood shuttling loop via Abcc3 transporter-mediated efflux and
      subsequent Oatp1a/1b-mediated liver uptake. We hypothesized that glucuronide
      conjugates of xenobiotics, such as the anticancer drug sorafenib, can also
      undergo hepatocyte hopping. Using transporter-deficient mouse models, we show
      here that sorafenib-glucuronide can be extruded from hepatocytes into the bile by
      Abcc2 or back into the systemic circulation by Abcc3, and that it can be taken up
      efficiently again into neighboring hepatocytes by Oatp1a/1b. We further
      demonstrate that sorafenib-glucuronide excreted into the gut lumen can be cleaved
      by microbial enzymes to sorafenib, which is then reabsorbed, supporting its
      persistence in the systemic circulation. Our results suggest broad relevance of a
      hepatocyte shuttling process known as "hepatocyte hopping"-a novel concept in
      clinical pharmacology-for detoxification of targeted cancer drugs that undergo
      hepatic glucuronidation, such as sorafenib.

PMID- 25952650
TI  - Genetic Identification of SEMA3F as an Antilymphangiogenic Metastasis Suppressor
      Gene in Head and Neck Squamous Carcinoma.
AB  - Head and neck squamous cell carcinomas (HNSCC) often metastasize to locoregional
      lymph nodes, and lymph node involvement represents one of the most important
      prognostic factors of poor clinical outcome. HNSCCs are remarkably
      lymphangiogenic and represent a clear example of a cancer that utilizes the
      lymphatic vasculature for malignant dissemination; however, the molecular
      mechanisms underlying lymphangiogenesis in HNSCC is still poorly understood. Of
      interest, we found that an axon guidance molecule, Semaphorin 3F (SEMA3F), is
      among the top 1% underexpressed genes in HNSCC, and that genomic loss of SEMA3F
      correlates with increased metastasis and decreased survival. SEMA3F acts on its
      coreceptors, plexins and neuropilins, among which neuropilin-2 (NRP2) is highly
      expressed in lymphatic endothelial cells (LEC) but not in oral epithelium and
      most HNSCCs. We show that recombinant SEMA3F promotes LEC collapse and potently
      inhibits lymphangiogenesis in vivo. By reconstituting all possible plexin and
      neuropilin combinations, we found that SEMA3F acts through multiple receptors,
      but predominantly requires NRP2 to signal in LECs. Using orthotopic HNSCC
      metastasis mouse models, we provide direct evidence that SEMA3F re-expression
      diminishes lymphangiogenesis and lymph node metastasis. Furthermore, analysis of
      a large tissue collection revealed that SEMA3F is progressively lost during HNSCC
      progression, concomitant with increased tumor lymphangiogenesis. SEMA3F is
      localized to 3p21, an early and frequently deleted locus in HNSCC and many other
      prevalent human malignancies. Thus, SEMA3F may represent an antilymphangiogenic
      metastasis suppressor gene widely lost during cancer progression, hence serving
      as a prognostic biomarker and an attractive target for therapeutic intervention
      to halt metastasis.

PMID- 25952651
TI  - Grade-Dependent Metabolic Reprogramming in Kidney Cancer Revealed by Combined
      Proteomics and Metabolomics Analysis.
AB  - Kidney cancer [or renal cell carcinoma (RCC)] is known as "the internist's tumor"
      because it has protean systemic manifestations, suggesting that it utilizes
      complex, nonphysiologic metabolic pathways. Given the increasing incidence of
      this cancer and its lack of effective therapeutic targets, we undertook an
      extensive analysis of human RCC tissue employing combined grade-dependent
      proteomics and metabolomics analysis to determine how metabolic reprogramming
      occurring in this disease allows it to escape available therapeutic approaches.
      After validation experiments in RCC cell lines that were wild-type or mutant for
      the Von Hippel-Lindau tumor suppressor, in characterizing higher-grade tumors, we
      found that the Warburg effect is relatively more prominent at the expense of the
      tricarboxylic acid cycle and oxidative metabolism in general. Further, we found
      that the glutamine metabolism pathway acts to inhibit reactive oxygen species, as
      evidenced by an upregulated glutathione pathway, whereas the beta-oxidation
      pathway is inhibited, leading to increased fatty acylcarnitines. In support of
      findings from previous urine metabolomics analyses, we also documented tryptophan
      catabolism associated with immune suppression, which was highly represented in
      RCC compared with other metabolic pathways. Together, our results offer a
      rationale to evaluate novel antimetabolic treatment strategies being developed in
      other disease settings as therapeutic strategies in RCC.

PMID- 25952652
TI  - A Digital Ethnography of Medical Students who Use Twitter for Professional
      Development.
AB  - BACKGROUND: While researchers have studied negative professional consequences of
      medical trainee social media use, little is known about how medical students
      informally use social media for education and career development. This knowledge
      may help future and current physicians succeed in the digital age. OBJECTIVE: We
      aimed to explore how and why medical students use Twitter for professional
      development. DESIGN: This was a digital ethnography. PARTICIPANTS: Medical
      student "superusers" of Twitter participated in the study APPROACH: The postings
      ("tweets") of 31 medical student superusers were observed for 8 months (May
      December 2013), and structured field notes recorded. Through purposive sampling,
      individual key informant interviews were conducted to explore Twitter use and
      values until thematic saturation was reached (ten students). Three faculty key
      informant interviews were also conducted. Ego network and subnetwork analysis of
      student key informants was performed. Qualitative analysis included inductive
      coding of field notes and interviews, triangulation of data, and analytic memos
      in an iterative process. KEY RESULTS: Twitter served as a professional tool that
      supplemented the traditional medical school experience. Superusers approached
      their use of Twitter with purpose and were mindful of online professionalism as
      well as of being good Twitter citizens. Their tweets reflected a mix of personal
      and professional content. Student key informants had a high number of followers.
      The subnetwork of key informants was well-connected, showing evidence of a social
      network versus information network. Twitter provided value in two major domains:
      access and voice. Students gained access to information, to experts, to a variety
      of perspectives including patient and public perspectives, and to communities of
      support. They also gained a platform for advocacy, control of their digital
      footprint, and a sense of equalization within the medical hierarchy. CONCLUSIONS:
      Twitter can serve as a professional tool that supplements traditional education.
      Students' practices and guiding principles can serve as best practices for other
      students as well as faculty.

PMID- 25952654
TI  - Persistent Intracardiac Thrombus: Could it be Cancer?

PMID- 25952653
TI  - A Successful Multifaceted Trial to Improve Hypertension Control in Primary Care:
      Why Did it Work?
AB  - BACKGROUND: It is important to understand which components of successful
      multifaceted interventions are responsible for study outcomes, since some
      components may be more important contributors to the intervention effect than
      others. OBJECTIVE: We conducted a mediation analysis to determine which of seven
      factors had the greatest effect on change in systolic blood pressure (BP) after 6
      months in a trial to improve hypertension control. DESIGN: The study was a
      preplanned secondary analysis of a cluster-randomized clinical trial. Eight
      clinics in an integrated health system were randomized to provide usual care to
      their patients (n = 222), and eight were randomized to provide a telemonitoring
      intervention (n = 228). PARTICIPANTS: Four hundred three of 450 trial
      participants completing the 6-month follow-up visit were included. INTERVENTIONS:
      Intervention group participants received home BP telemonitors and transmitted
      measurements to pharmacists, who adjusted medications and provided advice to
      improve adherence to medications and lifestyle modification via telephone visits.
      MAIN MEASURES: Path analytic models estimated indirect effects of the seven
      potential mediators of intervention effect (defined as the difference between the
      intervention and usual care groups in change in systolic BP from baseline to 6
      months). The potential mediators were change in home BP monitor use, number of BP
      medication classes, adherence to BP medications, physical activity, salt intake,
      alcohol use, and weight. KEY RESULTS: The difference in change in systolic BP was
      11.3 mmHg. The multivariable mediation model explained 47 % (5.3 mmHg) of the
      intervention effect. Nearly all of this was mediated by two factors: an increase
      in medication treatment intensity (24 %) and increased home BP monitor use (19
      %). The other five factors were not significant mediators, although medication
      adherence and salt intake improved more in the intervention group than in the
      usual care group. CONCLUSIONS: Most of the explained intervention effect was
      attributable to the combination of self-monitoring and medication
      intensification. High adherence at baseline and the relatively low intensity of
      resources directed toward lifestyle change may explain why these factors did not
      contribute to the improvement in BP.

PMID- 25952655
TI  - Capsule Commentary for Tsilimingras et al., Post-Discharge Adverse Events Among
      Urban and Rural Patients of an Urban Community Hospital: A Prospective Cohort
      Study.

PMID- 25952656
TI  - Adiponectin and its receptor signaling: an anti-cancer therapeutic target and its
      implications for anti-tumor immunity.
AB  - INTRODUCTION: Adiponectin (APN), produced by adipocytes, has direct anti
      diabetic, anti-atherogenic and anti-inflammatory properties. Circulating APN
      levels are lower in obesity, a disease state that is often associated with
      several malignancies. AREA COVERED: Increasingly, clinical data suggests that
      serum APN may have an important protective role in carcinogenesis. Certain cancer
      cell types express APN receptors and their downstream signaling pathways may
      influence cancer biology, possibly by regulating cell proliferation and inducing
      apoptosis. However, APN's role in the immune system, in particular to the anti
      tumor response, remains elusive. Therefore, this review critically addresses all
      controversies associated with the effect of APN on the immune system. EXPERT
      OPINION: Currently, the promise of interfering with APN and its receptor axis as
      a novel anti-cancer therapeutic target is rather encouraging. Greater
      understanding of the immunological side effects following this interference is
      crucial for the development of effective therapeutic strategies against obesity
      associated malignancies. APN receptor signaling on immune cells can blunt anti
      tumor immunity and induce tumor-specific tolerance. This may also have far
      reaching consequences on the application of APN as an anti-cancer agent.

PMID- 25952657
TI  - The microglia in healthy and diseased retina.
AB  - The microglia are the immune cells of the central nervous system and, also the
      retina. They fulfil several tasks of surveillance in the healthy retina. In case
      of an injury or disease, microglia become activated and tries to repair the
      damage. However, in a lot of cases it does not work, and microglia deteriorate
      the situation by releasing toxic and pro-inflammatory compounds. Moreover, they
      further promote degenerative processes by attacking and phagocytosing damaged
      neurones and photoreceptors that otherwise would possibly have the chance to
      survive. Such deleterious action of the microglia has been observed in
      degeneration of retinal ganglion cells and photoreceptors, and it takes place in
      hereditary diseases, infections as well as in case of traumatic or light
      injuries. Therefore, a number of attempts has been undertaken so far to inhibit
      the microglia, with varying success. The task remains to study behaviour of the
      microglia and their interaction with other retinal cell populations in more
      detail with respect to released factors and expressed receptors including the
      time points of the corresponding events. The goal has to be to find a better
      balance between helpful and detrimental actions of the microglia. 

PMID- 25952658
TI  - Phospholipid polymer electrodeposited on titanium inhibits platelet adhesion.
AB  - To develop metallic materials with thromboresistance, a block-type copolymer
      (PMbA) was immobilized onto a titanium surface with electrodeposition. The
      polymer was composed of a poly(2-(methacryloyloxy)ethyl phosphorylcholine (MPC))
      segment and a poly(2-aminoethylmethacrylate) segment, which was designed to
      electronically adsorb to the surface oxide layer on the titanium surface. We
      confirmed that the polymer was synthesized as expected by nuclear magnetic
      resonance and gel permeation chromatography. In a 0.26 mmol L(-1) PMbA solution
      adjusted to pH 11, -3.0 V (vs. an Ag/AgCl electrode) was applied to a titanium
      substrate for 300 s. The immobilization of PMbA on the titanium was confirmed
      with X-ray photoelectron spectroscopy and an atomic force microscope. The water
      contact angle and amount of adsorbed protein on the PMbA-modified surface were
      decreased. Thrombus formation was not observed all over the surface even when the
      surface was contacted with human blood without an anticoagulant. Therefore, PMbA
      covered the surface with even density and poly(MPC) segments in PMbA inhibited
      platelet adsorption. Electrodeposition with PMbA improves the blood compatibility
      of a titanium substrate in a simple process.

PMID- 25952659
TI  - Changes in fungal communities along a boreal forest soil fertility gradient.
AB  - Boreal forests harbour diverse fungal communities with decisive roles in
      decomposition and plant nutrition. Although changes in boreal plant communities
      along gradients in soil acidity and nitrogen (N) availability are well described,
      less is known about how fungal taxonomic and functional groups respond to soil
      fertility factors. We analysed fungal communities in humus and litter from 25
      Swedish old-growth forests, ranging from N-rich Picea abies stands to acidic and
      N-poor Pinus sylvestris stands. 454-pyrosequencing of ITS2 amplicons was used to
      analyse community composition, and biomass was estimated by ergosterol analysis.
      Fungal community composition was significantly related to soil fertility at the
      levels of species, genera/orders and functional groups. Ascomycetes dominated in
      less fertile forests, whereas basidiomycetes increased in abundance in more
      fertile forests, both in litter and humus. The relative abundance of mycorrhizal
      fungi in the humus layer remained high even in the most fertile soils. Tolerance
      to acidity and nitrogen deficiency seems to be of greater importance than plant
      carbon (C) allocation patterns in determining responses of fungal communities to
      soil fertility, in old-growth boreal forests. 

PMID- 25952661
TI  - Pharmacokinetic properties of BAY 81-8973, a full-length recombinant factor VIII.
AB  - INTRODUCTION: BAY 81-8973 is a full-length recombinant factor VIII (FVIII) with
      the same primary amino acid sequence as sucrose-formulated recombinant FVIII
      (rFVIII-FS) but is produced with advanced manufacturing technologies. AIM: To
      analyse the pharmacokinetics (PK) of BAY 81-8973 after single and multiple dosing
      across different age and ethnic groups in the LEOPOLD clinical trial programme.
      METHODS: The LEOPOLD trials enrolled patients with severe haemophilia A aged 12
      65 years (LEOPOLD I and II) or <=12 years (LEOPOLD Kids) with >=150 (LEOPOLD I
      and II) or >=50 (LEOPOLD Kids) exposure days to any FVIII product and no history
      of FVIII inhibitors. PK were assessed using chromogenic and one-stage assays
      (only chromogenic assay for LEOPOLD Kids) after a single 50-IU kg(-1) dose of BAY
      81-8973 and, in a subset of patients in LEOPOLD I, after repeated dosing.
      Pharmacokinetic analyses were also performed based on age (18 to 65, 12 to <18, 6
      to <12 and <6 years) and ethnicity (Asian and non-Asian). RESULTS:
      Pharmacokinetic assessments in the LEOPOLD I trial showed non-inferiority of BAY
      81-8973 vs. rFVIII-FS. The PK of BAY 81-8973 were comparable after single and
      multiple dosing. Age-based analysis in the three trials showed that plasma
      concentrations were slightly lower for children, but similar for adolescents
      compared with adults. Pharmacokinetic results were similar in the different
      ethnic groups. CONCLUSIONS: Results of the LEOPOLD trials show that the BAY 81
      8973 pharmacokinetic profile is non-inferior to rFVIII-FS. Similar BAY 81-8973
      pharmacokinetic values were observed following single and repeated dosing and
      across ethnic groups.

PMID- 25952662
TI  - Fetal Hyperthyroidism: Intrauterine Treatment with Carbimazole in Two Siblings.
AB  - Hyperthyroidism can manifest very early in fetal life (fetal thyrotoxicosis) or
      immediately after birth (neonatal thyrotoxicosis). The authors describe outcome
      of pregnancies in a woman with Graves' disease who received medical management
      and underwent subtotal thyroidectomy. The first pregnancy resulted in macerated
      stillbirth at 32 wk. Fetal tachycardia was followed by intrauterine death at 30
      wk in the second pregnancy and macerated stillbirth at 26 wk in the third
      pregnancy. Fetal tachycardia was detected at 17 wk in the fourth pregnancy.
      Treatment with carbimazole along with thyroxine was followed by a live birth at
      35 wk; but the baby developed severe fatal neonatal thyrotoxicosis with crisis on
      day 9 and died on day 12. Fetal tachycardia was noted in the fifth pregnancy as
      well and she was treated with carbimazole and thyroxine. She delivered a male
      baby at 37 wk. He developed neonatal hypothyroidism on day 8 which was controlled
      with thyroxine.

PMID- 25952663
TI  - Bilateral Chylothorax due to Brachiocephalic Vein Thrombosis in Relapsing
      Nephrotic Syndrome.

PMID- 25952660
TI  - Ventral hippocampal afferents to the nucleus accumbens regulate susceptibility to
      depression.
AB  - Enhanced glutamatergic transmission in the nucleus accumbens (NAc), a region
      critical for reward and motivation, has been implicated in the pathophysiology of
      depression; however, the afferent source of this increased glutamate tone is not
      known. The NAc receives glutamatergic inputs from the medial prefrontal cortex
      (mPFC), ventral hippocampus (vHIP) and basolateral amygdala (AMY). Here, we
      demonstrate that glutamatergic vHIP afferents to NAc regulate susceptibility to
      chronic social defeat stress (CSDS). We observe reduced activity in vHIP in mice
      resilient to CSDS. Furthermore, attenuation of vHIP-NAc transmission by
      optogenetic induction of long-term depression is pro-resilient, whereas acute
      enhancement of this input is pro-susceptible. This effect is specific to vHIP
      afferents to the NAc, as optogenetic stimulation of either mPFC or AMY afferents
      to the NAc is pro-resilient. These data indicate that vHIP afferents to NAc
      uniquely regulate susceptibility to CSDS, highlighting an important, novel
      circuit-specific mechanism in depression. 

PMID- 25952664
TI  - The development of a new disposable pipette extraction phase based on polyaniline
      composites for the determination of levels of antidepressants in plasma samples.
AB  - In the present work, a new stationary phase for disposable pipette extraction
      (DPX) based on composites of polyaniline and a styrene-divinylbenzene (SD)
      copolymer was applied to the analysis of fluoxetine and norfluoxetine in plasma
      samples using liquid chromatography and fluorescence detector (LC-FD). The DPX
      variables, such as number of draw/eject cycles, sample pH, type and volume of the
      desorption solvent, were optimized to established the sorption equilibrium and
      shorten the analysis time. Among the DPX evaluated variables, the higher
      extraction efficiency were obtained with 200 MUL of plasma mixed with 200 MUL of
      borate solution (pH 9), followed by liquid desorption of the drug with 200 MUL
      acetonitrile in a single cycle. The DPX/LC-FD method demonstrated a linear
      response over the dynamic range from 10 to 1000 ng mL(-1) for fluoxetine and from
      80 ng mL(-1) (LOQ) to 1000 ng mL(-1) for norfluoxetine with r(2)=0.997 and 0.998,
      respectively. The limit of quantification (LOQ) was 10 ng mL(-1) for fluoxetine
      and 80 ng mL(-1) for norfluoxetine. Based on the analytical validation results,
      the proposed method can be a useful tool for determining the fluoxetine and
      norfluoxetine levels in plasma samples from patients receiving therapeutic
      dosages.

PMID- 25952665
TI  - Tunable thick porous silica coating fabricated by multilayer-by-multilayer
      bonding of silica nanoparticles for open-tubular capillary chromatographic
      separation.
AB  - A simple coating procedure employing a multilayer-by-multilayer process to modify
      the inner surface of bare fused-silica capillaries with silica nanoparticles was
      established. The silica nanoparticles were adsorbed onto the capillary wall via a
      strong electrostatic interaction between amino functional groups and silica
      particles. The thickness of the coating could be tuned from 130 to 600 nm by
      increasing the coating cycles from one to three. Both the retention factor and
      the resolution were greatly increased with increasing coating cycles. The loading
      capacity determined by naphthalene in the column with three coating cycles is
      152.1 pmol. The effects of buffer concentration and pH value on the stability of
      the coating were evaluated. The retention reproducibility of the separation of
      toluene was 0.8, 1.2, 2.3, and 4.5%, respectively, for run-to-run, day-to-day,
      column-to-column, and batch-to-batch, respectively. The chromatographic
      performance of these columns was evaluated by both capillary liquid
      chromatography and open-tubular capillary electrochromatography (OT-CEC).
      Separation of aromatic hydrocarbons in the column with three coating cycles
      provided high theoretical plate numbers (up to 269,280 plates m(-1) for toluene)
      and short separation time (<15 min) by using OT-CEC mode. The method was also
      used to separate egg white proteins. Both acidic and basic proteins as well as
      four glycoisoforms were separated in a single run.

PMID- 25952666
TI  - Interfacing microchip isoelectric focusing with on-chip electrospray ionization
      mass spectrometry.
AB  - In this work, we demonstrate the interfacing of microchip capillary isoelectric
      focusing (cIEF) with online mass spectrometric (MS) detection via a fully
      integrated, on-chip sheath flow electrospray ionization (ESI) emitter. Thanks to
      the pH-dependent surface charge of the SU-8 polymer cIEF can be successfully run
      in native SU-8 microchannels without need for surface pretreatment prior to
      analysis. On the other hand, the inherent electroosmotic flow (EOF) taking place
      in SU-8 microchannels at high pH can be exploited to electrokinetic mobilization
      of the focused pH gradient toward the MS and no external pumps are required. In
      addition to direct coupling of a cIEF separation channel to an ESI emitter, we
      developed a two-dimensional separation chip for two-step, multiplex cIEF
      transient-isotachophoretic (tITP) separation. In this case, cIEF is performed in
      the first dimension (effective L=20mm) and tITP in the second dimension (L=35mm)
      followed by ESI/MS. As a result, the migration order is affected by both the pI
      values (cIEF) and the intrinsic electrophoretic mobilities (tITP) of the sample
      components. The selectivity of the separation system was shown to be different
      from pure cIEF or pure ITP, which allows at best for baseline separation of two
      compounds with nearly identical pI values. The repeatabilities of the migration
      times of the two-step cIEF-tITP separation were 3.1-6.8% RSD (n=3). Thanks to the
      short separation channel, relatively short focusing times of 60-270s (depending
      on the applied focusing potential) were sufficient for establishment of the pH
      gradient and cIEF separation of the sample components, yielding total analysis
      times (including loading, focusing, and mobilization) well below 10min. 

PMID- 25952667
TI  - A Fresh Look on T-Box Factor Action in Early Embryogenesis (T-Box Factors in
      Early Development).
AB  - T-Box transcription factors are expressed throughout the gestational period and
      coordinate a variety of embryonic events that enable proper development, from the
      first differentiation of embryonic and extraembryonic tissues until final
      organogenesis. Although the T-Box gene family comprises essential roles in early
      cellular differentiation, in adult tissues it has also been associated with
      cancer development. In spite of their common T-Box regulatory binding domain, T
      Box family members utilize different cofactors and different spatiotemporal
      expression patterns to confer their specificity in diverse developmental
      processes. The earliest expression note of T-Box factors can be observed even
      before fertilization in primordial germ cells and just after zygotic gene
      activation (around the eight-cell blastomere stage). Thus, particularly the early
      stages of development are highly influenced by these key regulators in line with
      the notion that T-Box mutations lead to developmental disorders and even
      lethality. In this review, we summarize recently acquired findings on T-Box
      factors to provide a comprehensive overview on their role during early
      embryogenesis. 

PMID- 25952669
TI  - In-cell infection: bringing uninvited guests.
AB  - Cell-in-cell structures resulting from live cell engulfment were identified more
      than 100 years ago, but their physiological significance has remained largely
      obscure. Now Ni et al. identify a new role for cell-in-cell structure formation,
      called "in-cell infection" that spreads Epstein-Barr virus from infected B cells
      to epithelial cells, an activity that may predispose to cancer. 

PMID- 25952668
TI  - Methylation-dependent loss of RIP3 expression in cancer represses programmed
      necrosis in response to chemotherapeutics.
AB  - Receptor-interacting protein kinase-3 (RIP3 or RIPK3) is an essential part of the
      cellular machinery that executes "programmed" or "regulated" necrosis. Here we
      show that programmed necrosis is activated in response to many chemotherapeutic
      agents and contributes to chemotherapy-induced cell death. However, we show that
      RIP3 expression is often silenced in cancer cells due to genomic methylation near
      its transcriptional start site, thus RIP3-dependent activation of MLKL and
      downstream programmed necrosis during chemotherapeutic death is largely
      repressed. Nevertheless, treatment with hypomethylating agents restores RIP3
      expression, and thereby promotes sensitivity to chemotherapeutics in a RIP3
      dependent manner. RIP3 expression is reduced in tumors compared to normal tissue
      in 85% of breast cancer patients, suggesting that RIP3 deficiency is positively
      selected during tumor growth/development. Since hypomethylating agents are
      reasonably well-tolerated in patients, we propose that RIP3-deficient cancer
      patients may benefit from receiving hypomethylating agents to induce RIP3
      expression prior to treatment with conventional chemotherapeutics. 

PMID- 25952670
TI  - The chromosome copy number of the hyperthermophilic archaeon Thermococcus
      kodakarensis KOD1.
AB  - The euryarchaeon Thermococcus kodakarensis is a well-characterized anaerobic
      hyperthermophilic heterotroph and due to the availability of genetic engineering
      systems it has become one of the model organisms for studying Archaea. Despite
      this prominent role among the Euryarchaeota, no data about the ploidy level of
      this species is available. While polyploidy has been shown to exist in various
      Euryarchaeota, especially Halobacteria, the chromosome copy number of species
      belonging to one of the major orders within that phylum, i.e., the Thermococcales
      (including Thermococcus spp. and Pyrococcus spp.), has never been determined.
      This prompted us to investigate the chromosome copy number of T. kodakarensis. In
      this study, we demonstrate that T. kodakarensis is polyploid with a chromosome
      copy number that varies between 7 and 19 copies, depending on the growth phase.
      An apparent correlation between the presence of histones and polyploidy in
      Archaea is observed.

PMID- 25952671
TI  - Thermophilic prokaryotic communities inhabiting the biofilm and well water of a
      thermal karst system located in Budapest (Hungary).
AB  - In this study, scanning electron microscopy (SEM) and 16S rRNA gene-based
      phylogenetic approach were applied to reveal the morphological structure and
      genetic diversity of thermophilic prokaryotic communities of a thermal karst well
      located in Budapest (Hungary). Bacterial and archaeal diversity of the well water
      (73.7  degrees C) and the biofilm developed on the inner surface of an outflow
      pipeline of the well were studied by molecular cloning method. According to the
      SEM images calcium carbonate minerals serve as a surface for colonization of
      bacterial aggregates. The vast majority of the bacterial and archaeal clones
      showed the highest sequence similarities to chemolithoautotrophic species. The
      bacterial clone libraries were dominated by sulfur oxidizer Thiobacillus
      (Betaproteobacteria) in the water and Sulfurihydrogenibium (Aquificae) in the
      biofilm. A relatively high proportion of molecular clones represented genera
      Thermus and Bellilinea in the biofilm library. The most abundant phylotypes both
      in water and biofilm archaeal clone libraries were closely related to
      thermophilic ammonia oxidizer Nitrosocaldus and Nitrososphaera but phylotypes
      belonging to methanogens were also detected. The results show that in addition to
      the bacterial sulfur and hydrogen oxidation, mainly archaeal ammonia oxidation
      may play a decisive role in the studied thermal karst system. 

PMID- 25952673
TI  - Strength analysis of a three-unit dental bridge framework with the Finite Element
      Method.
AB  - PURPOSE: The aim of the study was to analyse the strength of a prosthetic bridge
      with variable geometry in the connectors between the span and the retention
      elements on the pillar teeth crowns. METHODS: Research was carried using the
      Finite Elements Method (FEM) on a model of the bridge in the anterior teeth arch
      in the field 21-22-23, obtained using a contact scanner and computer aided design
      (CAD) system, with four different cross-sectional areas of the connectors: 4.0,
      5.0, 5.5, and 6.0 mm2. For that purpose, the impact of the properties of selected
      metal alloys on the deflection of the prosthesis was analysed. RESULTS: On the
      basis of the analyses, it was found that when the loading force acted obliquely,
      the stress was 19% higher compared to the stress with a loading vertical force.
      In the case of connectors with the smallest cross-sectional area, the stress
      exceeded permissible value (with safety factor n = 2) for one of the alloys.
      CONCLUSIONS: Deflection of the bridges tested changed depending on the connector
      cross-section and the elastic modulus of the selected material.

PMID- 25952674
TI  - Treatment management and glycaemic control in a sample of 60 frail elderly
      diabetics with comorbidities. A retrospective chart review.

PMID- 25952672
TI  - Transcriptional profiling provides insights into metronomic cyclophosphamide
      activated, innate immune-dependent regression of brain tumor xenografts.
AB  - BACKGROUND: Cyclophosphamide treatment on a six-day repeating metronomic schedule
      induces a dramatic, innate immune cell-dependent regression of implanted gliomas.
      However, little is known about the underlying mechanisms whereby metronomic
      cyclophosphamide induces innate immune cell mobilization and recruitment, or
      about the role of DNA damage and cell stress response pathways in eliciting the
      immune responses linked to tumor regression. METHODS: Untreated and metronomic
      cyclophosphamide-treated human U251 glioblastoma xenografts were analyzed on
      human microarrays at two treatment time points to identify responsive tumor cell
      specific factors and their upstream regulators. Mouse microarray analysis across
      two glioma models (human U251, rat 9L) was used to identify host factors and gene
      networks that contribute to the observed immune and tumor regression responses.
      RESULTS: Metronomic cyclophosphamide increased expression of tumor cell-derived
      DNA damage, cell stress, and cell death genes, which may facilitate innate immune
      activation. Increased expression of many host (mouse) immune networks was also
      seen in both tumor models, including complement components, toll-like receptors,
      interferons, and cytolysis pathways. Key upstream regulators activated by
      metronomic cyclophosphamide include members of the interferon, toll-like
      receptor, inflammatory response, and PPAR signaling pathways, whose activation
      may contribute to anti-tumor immunity. Many upstream regulators inhibited by
      metronomic cyclophosphamide, including hypoxia-inducible factors and MAP kinases,
      have glioma-promoting activity; their inhibition may contribute to the
      therapeutic effectiveness of the six-day repeating metronomic cyclophosphamide
      schedule. CONCLUSIONS: Large numbers of responsive cytokines, chemokines and
      immune regulatory genes linked to innate immune cell recruitment and tumor
      regression were identified, as were several immunosuppressive factors that may
      contribute to the observed escape of some tumors from metronomic CPA-induced,
      immune-based regression. These factors may include useful biomarkers that
      facilitate discovery of clinically effective immunogenic metronomic drugs and
      treatment schedules, and the selection of patients most likely to be responsive
      to immunogenic drug scheduling.

PMID- 25952677
TI  - Intramolecular pyridine-based frustrated Lewis-pairs.
AB  - Deprotonation of the methylpyridines 2,6-lutidine, 2-picoline, 4-dimethylamino
      2,6-dimethylpyridine as well as 2,6-dimethyl-4-(piperidine-1-yl)pyridine with n
      butyllithium or n-butyllithium/KO-t-Bu at the methyl positions led to the
      corresponding organolithium or -potassium compounds. Treatment with ClB(C6F5)2
      resulted in formation of the 2-borylmethylpyridines py-CH2-B(C6F5)2. They are
      monomeric and form intramolecular B-N bonds and four-membered rings. A short
      intramolecular B-N distance was observed in the crystal structure of the
      dimethylamino-functionalized derivative and proposed to be responsible for the
      low reactivity of the products towards hydrogen, thf, acetonitrile and CO2.
      Hydroboration of 6-tert-butyl-2-but-4'-enylpyridine with HB(C6F5)2 led to the
      corresponding hydroboration product t-Bu-py-(CH2)4-B(C6F5)2 which shows no
      intramolecular B-N bond formation due to steric crowding. H/D-scrambling
      experiments with a H2/D2 mixture revealed its reactivity towards hydrogen. 

PMID- 25952675
TI  - Osteoinduction and proliferation of bone-marrow stromal cells in three
      dimensional poly (epsilon-caprolactone)/ hydroxyapatite/collagen scaffolds.
AB  - BACKGROUND: Osteoinduction and proliferation of bone-marrow stromal cells (BMSCs)
      in three-dimensional (3D) poly(epsilon-caprolactone) (PCL) scaffolds have not
      been studied throughly and are technically challenging. This study aimed to
      optimize nanocomposites of 3D PCL scaffolds to provide superior adhesion,
      proliferation and differentiation environment for BMSCs in this scenario.
      METHODS: BMSCs were isolated and cultured in a novel 3D tissue culture
      poly(epsilon-caprolactone) (PCL) scaffold coated with poly-lysine, hydroxyapatite
      (HAp), collagen and HAp/collagen. Cell morphology was observed and BMSC
      biomarkers for osteogenesis, osteoblast differentiation and activation were
      analyzed. RESULTS: Scanning Electron Microscope (SEM) micrographs showed that
      coating materials were uniformly deposited on the surface of PCL scaffolds and
      BMSCs grew and aggregated to form clusters during 3D culture. Both mRNA and
      protein levels of the key players of osteogenesis and osteoblast differentiation
      and activation, including runt-related transcription factor 2 (Runx2), alkaline
      phosphates (ALP), osterix, osteocalcin, and RANKL, were significantly higher in
      BMSCs seeded in PCL scaffolds coated with HAp or HAp/collagen than those seeded
      in uncoated PCL scaffolds, whereas the expression levels were not significantly
      different in collagen or poly-lysine coated PCL scaffolds. In addition, poly
      lysine, collagen, HAp/collagen, and HAp coated PCL scaffolds had significantly
      more viable cells than uncoated PCL scaffolds, especially scaffolds with
      HAp/collagen and collagen-alone coatings. That BMSCs in HAp or HAp/collagen PCL
      scaffolds had remarkably higher ALP activities than those in collagen-coated
      alone or uncoated PCL scaffolds indicating higher osteogenic differentiation
      levels of BMSCs in HAp or HAp/collagen PCL scaffolds. Moreover, morphological
      changes of BMSCs after four-week of 3D culture confirmed that BMSCs successfully
      differentiated into osteoblast with spread-out phenotype in HAp/collagen coated
      PCL scaffolds. CONCLUSION: This study showed a proof of concept for preparing
      biomimetic 3D poly (epsilon-caprolactone)/ hydroxyapatite/collagen scaffolds with
      excellent osteoinduction and proliferation capacity for bone regeneration.

PMID- 25952676
TI  - Exploring the Underdiagnosis and Prevalence of Autism Spectrum Conditions in
      Beijing.
AB  - Previous studies reported that the prevalence of Autism Spectrum Conditions (ASC)
      in mainland China is much lower than estimates from developed countries (around
      1%). The aim of the study is to apply current screening and standardized
      diagnostic instruments to a Chinese population to establish a prevalence estimate
      of ASC in an undiagnosed population in mainland China. We followed the design
      development used previously in the UK published in 2009 by Baron-Cohen and
      colleagues. The Mandarin Childhood Autism Spectrum Test (CAST) was validated by
      screening primary school pupils (n = 737 children age 6-10 years old) in Beijing
      and by conducting diagnostic assessments using the Autism Diagnostic Observation
      Schedule and the Autism Diagnostic Interview-Revised. The prevalence estimate was
      generated after adjusting and imputing for missing values using the inverse
      probability weighting. Response was high (97%). Using the UK cutoff (>=15), CAST
      performance has 84% sensitivity and 96% specificity (95% confidence interval
      [CI]: 46, 98, and 96, 97, respectively). Six out of 103 children, not previously
      diagnosed, were found to the meet diagnostic criteria (8.5 after adjustment, 95%
      CI: 1.6, 15.4). The preliminary prevalence in an undiagnosed primary school
      population in mainland China was 119 per 10,000 (95% CI: 53, 265). The utility of
      CAST is acceptable as a screening instrument for ASC in large epidemiological
      studies in China. Using a comparable method, the preliminary prevalence estimate
      of ASC in mainland China is similar to that of those from developed countries.

PMID- 25952678
TI  - Reconsidering 'ethics' and 'quality' in healthcare research: the case for an
      iterative ethical paradigm.
AB  - BACKGROUND: UK-based research conducted within a healthcare setting generally
      requires approval from the National Research Ethics Service. Research ethics
      committees are required to assess a vast range of proposals, differing in both
      their topic and methodology. We argue the methodological benchmarks with which
      research ethics committees are generally familiar and which form the basis of
      assessments of quality do not fit with the aims and objectives of many forms of
      qualitative inquiry and their more iterative goals of describing social
      processes/mechanisms and making visible the complexities of social practices. We
      review current debates in the literature related to ethical review and social
      research, and illustrate the importance of re-visiting the notion of ethics in
      healthcare research. DISCUSSION: We present an analysis of two contrasting
      paradigms of ethics. We argue that the first of these is characteristic of the
      ways that NHS ethics boards currently tend to operate, and the second is an
      alternative paradigm, that we have labelled the 'iterative' paradigm, which draws
      explicitly on methodological issues in qualitative research to produce an
      alternative vision of ethics. We suggest that there is an urgent need to re-think
      the ways that ethical issues are conceptualised in NHS ethical procedures. In
      particular, we argue that embedded in the current paradigm is a restricted notion
      of 'quality', which frames how ethics are developed and worked through. Specific,
      pre-defined outcome measures are generally seen as the traditional marker of
      quality, which means that research questions that focus on processes rather than
      on 'outcomes' may be regarded as problematic. We show that the alternative
      'iterative' paradigm offers a useful starting point for moving beyond these
      limited views. SUMMARY: We conclude that a 'one size fits all' standardisation of
      ethical procedures and approach to ethical review acts against the production of
      knowledge about healthcare and dramatically restricts what can be known about the
      social practices and conditions of healthcare. Our central argument is that
      assessment of ethical implications is important, but that the current paradigm
      does not facilitate an adequate understanding of the very issues it aims to
      invigilate.

PMID- 25952679
TI  - Iron status of schoolchildren (6-15 years) and associated factors in rural
      Nigeria.
AB  - BACKGROUND: Schoolchildren are vulnerable to anaemia because of their higher iron
      need to meet the demands of puberty and adolescence. OBJECTIVE: The survey
      determined the haemoglobin levels of schoolchildren aged 6-15 years and the
      factors affecting their haemoglobin status. DESIGN: Data were obtained through a
      cross sectional survey of 450 randomly selected schoolchildren in Ede-Oballa,
      Nsukka, Enugu State, Nigeria. Ninety were selected for clinical examination,
      biochemical tests, and nutrient intake study. Haemoglobin, malaria, and stool
      analysis were carried out by the cyanmethaemoglobin, thin blood film, and wet
      mount direct methods, respectively. Iron intake was determined by a three-day
      weighed food intake. RESULTS: Results showed that the schoolchildren had pallor
      (35.6%), brittle hair (31.1%), koilonychia (2.2%), oedema (4.4%) and sore/smooth
      tongue (7.8%). The children also had malaria (58.9%) and Entamoeba histolytica
      (42.2%), hookworm (36.7%), tapeworm (35.6%), whipworm (34.5%), and roundworm
      (27.9%) infestations. Iron intake was inadequate (<100% of recommended nutrient
      intake) for most of the children. The mean haemoglobin levels of the
      schoolchildren were low. The 6-9, 10-12, and 13-15 year olds had 9.0, 9.1, and
      9.3 g/dl, respectively. Most (85.5%) of them had anaemia. Moderate anaemia was
      prevalent in 62.2%. Severe anaemia affected the 6-9 year olds more. Malaria
      (P<0.001), Entamoeba histolytica (P<0.01), hookworm (P<0.05), tapeworm (P<0.01),
      and whipworm (P<0.001) caused significant reduction in haemoglobin level. Age
      (b=1.284, P<0.05), birth order (b=-0.629, P<0.01), frequency of illness attack
      (b=-1.372, P<0.01), household size (b=-0.526, P<0.05), and frequency of skipping
      breakfast (b=-1.542, P<0.001) were factors that influenced the haemoglobin status
      of the children. CONCLUSION: The schoolchildren had poor iron status as a result
      of consumption of plant sources of iron with low bioavailability, parasitic
      infections, birth order, skipping of breakfast, large household size, and
      frequent bouts of illnesses.

PMID- 25952681
TI  - Prioritization of catchments based on soil erosion using remote sensing and GIS.
AB  - Water and soil are the most essential natural resources for socioeconomic
      development and sustenance of life. A study of soil and water dynamics at a
      watershed level facilitates a scientific approach towards their conservation and
      management. Remote sensing and Geographic Information System are tools that help
      to plan and manage natural resources on watershed basis. Studies were conducted
      for the formulation of catchment area treatment plan based on watershed
      prioritization with soil erosion studies using remote sensing techniques,
      corroborated with Geographic Information System (GIS), secondary data and ground
      truth information. Estimation of runoff and sediment yield is necessary in
      prioritization of catchment for the design of soil conservation structures and
      for identifying the critical erosion-prone areas of a catchment for
      implementation of best management plan with limited resources. The Universal Soil
      Loss Equation, Sediment Yield Determination and silt yield index methods are used
      for runoff and soil loss estimation for prioritization of the catchments. On the
      basis of soil erosion classes, the watersheds were grouped into very high, high,
      moderate and low priorities. High-priority watersheds need immediate attention
      for soil and water conservation, whereas low-priority watershed having good
      vegetative cover and low silt yield index may not need immediate attention for
      such treatments. 

PMID- 25952680
TI  - Comparative transcriptomics uncovers alternative splicing changes and signatures
      of selection from maize improvement.
AB  - BACKGROUND: Alternative splicing (AS) is an important regulatory mechanism that
      greatly contributes to eukaryotic transcriptome diversity. A substantial amount
      of evidence has demonstrated that AS complexity is relevant to eukaryotic
      evolution, development, adaptation, and complexity. In this study, six teosinte
      and ten maize transcriptomes were sequenced to analyze AS changes and signatures
      of selection in maize domestication and improvement. RESULTS: In maize and
      teosinte, 13,593 highly conserved genes, including 12,030 multiexonic genes, were
      detected. By identifying AS isoforms from mutliexonic genes, we found that AS
      types were not significantly different between maize and teosinte. In addition,
      the two main AS types (intron retention and alternative acceptor) contributed to
      more than 60% of the AS events in the two species, but the average unique AS
      events per each alternatively spliced gene in maize (4.12) was higher than that
      in teosinte (2.26). Moreover, 94 genes generating 98 retained introns with
      transposable element (TE) sequences were detected in maize, which is far more
      than 9 retained introns with TEs detected in teosinte. This indicates that TE
      insertion might be an important mechanism for intron retention in maize.
      Additionally, the AS levels of 3864 genes were significantly different between
      maize and teosinte. Of these, 151 AS level-altered genes that are involved in
      transcriptional regulation and in stress responses are located in regions that
      have been targets of selection during maize improvement. These genes were
      inferred to be putatively improved genes. CONCLUSIONS: We suggest that both maize
      and teosinte share similar AS mechanisms, but more genes have increased AS
      complexity during domestication from teosinte to maize. Importantly, a subset of
      AS level-increased genes that encode transcription factors and stress-responsive
      proteins may have been selected during maize improvement.

PMID- 25952682
TI  - Hospitalized fall-related injury trends in Sweden between 2001 and 2010.
AB  - Previous studies have indicated increasing trends of hospitalized fall-related
      injuries amongst elderly. Whether this is true also in Sweden is unknown though
      it is important to study considering the potential societal impact. Data were
      obtained regarding hospitalized injuries with falls as external cause among those
      aged 65 years and above with information on injury type, gender and age, on a
      yearly basis, from 2001 to 2010. Age- and sex-specific incidence rates were
      calculated (per 100,000 population) for all fall-related injuries, and for each
      injury type and trend lines were drawn. Linear regression analyses and percentage
      change were calculated for the types of fall-related injuries. A decreasing
      incidence was observed in the younger age groups (65-79 years) with greater
      decreases amongst women (women: -14.6%, men 65-79 years: -10.5%). However,
      increasing rates were observed in the older age group (80 years and above), with
      greater increases amongst men (women: 4.3%, men: 11.4%). Superficial injuries
      showed greater increases than fractures amongst those aged 80 years and above.
      This study indicates that older elderly in Sweden are increasingly being
      hospitalized for less serious injuries. This changing injury panorama is
      important to include in the future planning of both health care and fall-related
      prevention. 

PMID- 25952683
TI  - How to assess eyes and vision in infants and preschool children.

PMID- 25952684
TI  - Disclosure of research results in genetic studies of Parkinson's disease caused
      by LRRK2 mutations.
AB  - With the advent of large genetic studies examining both symptomatic and
      asymptomatic individuals, whether and how to disclose genetic research results
      have become pressing questions. The need is particularly acute in the case of
      LRRK2 research: Movement centers worldwide are recruiting cohorts of individuals
      with Parkinson's disease (PD) and their family members, including asymptomatic
      carriers. Clinical features and treatment are complex and evolving, and
      disclosure policies vary at different sites and have been modified during the
      course of some studies. We present the major ethical principles of autonomy,
      beneficence, nonmaleficence, and honesty that should guide disclosure policies in
      studies of families with LRRK2 mutations. We make recommendations regarding
      genetic counseling, policies of either active or passive disclosure,
      responsibilities of funders to budget for genetic counseling, clinical genetic
      testing where locally required for disclosure, and aspects of study design to
      avoid mandatory disclosure whenever feasible. (c) 2015 International Parkinson
      and Movement Disorder Society. 

PMID- 25952685
TI  - Both FOXO3a and FOXO1 are involved in the HGF-protective pathway against
      apoptosis in endothelial cells.
AB  - Hepatocyte growth factor (HGF) was identified as an endogenous tissue protective
      agent against apoptosis in many cell types. The mechanism by which HGF protects
      primary endothelial cells (ECs) has not yet been completely elucidated. FOXO1 and
      FOXO3a, two members of the FOXO family, are the most abundant FOXO isoforms in
      mature endothelial cells. In this study, we aimed to explore whether FOXO1 and
      FOXO3a play similar roles in HGF-mediated protection against apoptosis in mature
      endothelial cells. Our result showed that HGF prevented ECs from oxidative-stress
      induced apoptosis in part by inducing the phosphorylation of FOXO proteins. FOXO1
      and FOXO3a are equally important in this process by regulating the expression of
      Bim, PUMA, FasL, and TRAIL. 

PMID- 25952686
TI  - Inorganic nitrite improves components of the metabolic syndrome independent of
      weight change in a murine model of obesity and insulin resistance.
AB  - Nitrite acts as an endocrine source of bioactive nitric oxide, impacting vascular
      reactivity, angiogenesis and cytoprotection. Nitrite has recently been shown to
      have a metabolic role although its effects and mechanisms of action in the obese
      insulin-resistant state are unknown. We examined glucose tolerance and insulin
      secretion using the frequently sampled intravenous glucose tolerance test and
      insulin sensitivity using the hyperinsulinaemic euglycaemic clamp in obese male
      ob(lep) mice administered nitrite (100 mg kg(-1) day(-1) ) or saline (control)
      for 7 days and compared responses to the known insulin-sensitizing effects of
      rosiglitazone (6 mg kg(-1) day(-1) ). Under weight-matched conditions, nitrite
      lowered blood pressure relative to saline and rosiglitazone, whereas only
      rosiglitazone was effective at reducing hepatic glucose output and basal blood
      glucose. Both nitrite and rosiglitazone produced improvements, relative to
      saline, in glucose tolerance (12,524 +/- 602, 12,811 +/- 692 vs.14,428 +/- 335 mg
      (dl min)(-1) , respectively; P < 0.05) and insulin sensitivity (8.6 +/- 0.7, 7.9
      +/- 0.3 vs. 6.6 +/- 0.5 mg kg(-1) min(-1) , respectively; P < 0.001), but there
      was no effect on insulin secretion. Nitrite exhibited an uncoupling of
      mitochondrial respiration and a decrease in ATP generation in muscle that was
      independent of mitochondrial biogenesis or activation of uncoupling proteins.
      There was no insulin-stimulated phosphorylation of Akt, but nitrite increased the
      phosphorylation of AMP-activated protein kinase. We conclude that nitrite
      improves two key components of the metabolic syndrome, blood pressure and insulin
      sensitivity, independent of weight and with effectiveness comparable to
      rosiglitazone.

PMID- 25952688
TI  - Targeted analysis of recombinant NF kappa B (RelA/p65) by denaturing and native
      top down mass spectrometry.
AB  - Measuring post-translational modifications on transcription factors by targeted
      mass spectrometry is hampered by low protein abundance and inefficient isolation.
      Here, we utilized HaloTag technology to overcome these limitations and evaluate
      various top down mass spectrometry approaches for measuring NF-kappaB p65
      proteoforms isolated from human cells. We show isotopic resolution of N
      terminally acetylated p65 and determined it is the most abundant proteoform
      expressed following transfection in 293T cells. We also show MS(1) evidence for
      monophosphorylation of p65 under similar culture conditions and describe a high
      propensity for p65 proteoforms to fragment internally during beam-style MS(2)
      fragmentation; up to 71% of the fragment ions could be matched as internals in
      some fragmentation spectra. Finally, we used native spray mass spectrometry to
      measure proteins copurifying with p65 and present evidence for the native
      detection of p65, 71kDa heat shock protein, and p65 homodimer. Collectively, our
      work demonstrates the efficient isolation and top down mass spectrometry analysis
      of p65 from human cells, and we discuss the perturbations of overexpressing
      tagged proteins to study their biochemistry. This article is part of a Special
      Issue entitled: Protein Species. BIOLOGICAL SIGNIFICANCE: Characterizing
      transcription factor proteoforms in human cells is of high value to the field of
      molecular biology; many agree that post-translational modifications and
      combinations thereof play a critical role in modulating transcription factor
      activity. Thus, measuring these modifications promises increased understanding of
      molecular mechanisms governing the regulation of complex gene expression
      outcomes. To date, comprehensive characterization of transcription factor
      proteoforms within human cells has eluded measurement, owing primarily-with
      regard to top down mass spectrometry-to large protein size and low relative
      abundance. Here, we utilized HaloTag technology and recombinant protein
      expression to overcome these limitations and show top down mass spectrometry
      characterization of proteoforms of the 60kDa NF-kB protein, p65. By optimizing
      the analytical procedure (i.e. purification, MS(1), and MS(2)), our results make
      important progress toward the ultimate goal of targeted transcription factor
      characterization from endogenous loci.

PMID- 25952689
TI  - The Benefits of 3D Mapping Systems for Ablation of WPW in Children.

PMID- 25952687
TI  - Identification of differentially expressed serum proteins in gastric
      adenocarcinoma.
AB  - Gastric adenocarcinoma is an aggressive cancer with poor prognosis. Blood based
      biomarkers of gastric cancer have the potential to improve diagnosis and
      monitoring of these tumors. Proteins that show altered levels in the circulation
      of gastric cancer patients could prove useful as putative biomarkers. We used an
      iTRAQ-based quantitative proteomic approach to identify proteins that show
      altered levels in the sera of patients with gastric cancer. Our study resulted in
      identification of 643 proteins, of which 48 proteins showed increased levels and
      11 proteins showed decreased levels in serum from gastric cancer patients
      compared to age and sex matched healthy controls. Proteins that showed increased
      expression in gastric cancer included inter-alpha-trypsin inhibitor heavy chain
      H4 (ITIH4), Mannose-binding protein C (MBL2), sex hormone-binding globulin
      (SHBG), insulin-like growth factor-binding protein 2 (IGFBP2), serum amyloid A
      protein (SAA1), Orosomucoid 1 (ORM1) and extracellular superoxide dismutase [Cu
      Zn] (SOD3). We used multiple reaction monitoring assays and validated elevated
      levels of ITIH4 and SAA1 proteins in serum from gastric cancer patients.
      BIOLOGICAL SIGNIFICANCE: Gastric cancer is a highly aggressive cancer associated
      with high mortality. Serum-based biomarkers are of considerable interest in
      diagnosis and monitoring of various diseases including cancers. Gastric cancer is
      often diagnosed at advanced stages resulting in poor prognosis and high
      mortality. Pathological diagnosis using biopsy specimens remains the gold
      standard for diagnosis of gastric cancer. Serum-based biomarkers are of
      considerable importance as they are minimally invasive. In this study, we carried
      out quantitative proteomic profiling of serum from gastric cancer patients to
      identify proteins that show altered levels in gastric cancer patients. We
      identified more than 50 proteins that showed altered levels in gastric cancer
      patient sera. Validation in a large cohort of well classified patient samples
      would prove useful in identifying novel blood based biomarkers for gastric
      cancers. This article is part of a Special Issue entitled: Proteomics in India.

PMID- 25952690
TI  - Evaluation of the impact of celiac disease and its dietary manipulation on
      children and their caregivers.
AB  - BACKGROUND: Lifelong dietary abstinence of gluten is the only treatment available
      for celiac disease. This is not only challenging but also leads to several
      psychosocial morbidities and affects the quality of life of children and their
      parents. METHODS: An observational study was conducted on 50 children (5-18
      years) diagnosed with celiac disease on gluten-free diet for at least 6 months
      and their parents to evaluate of the impact of celiac disease and its dietary
      manipulation on them. The quality of life was assessed by applying celiac disease
      specific questionnaire. Dietary compliant and noncompliant groups were compared
      to assess the factors leading to poor compliance. Anthropometric parameters were
      utilized to ascertain clinical response. RESULTS: Fifty children with a mean age
      of 9.06 years were enrolled. Seventy-four percent of the children were compliant.
      In the compliant group, height and weight correlated with dietary compliance (p =
      0.0087 and p = 0.023). Dietary compliance was found to be better in adolescent
      males and single child and those living in nuclear families. Quality of life was
      found to be higher among parents of noncompliant children (quality of life score:
      63) as compared to the compliant children (quality of life score: 59). The
      acceptance of celiac disease was better among children whose parents had a higher
      level of education. The scale diet proved to be a useful indicator for evaluating
      compliance among children (p = 0.0036). CONCLUSIONS: Noncompliance to gluten-free
      diet was noted in 24 % of children with celiac disease.

PMID- 25952692
TI  - The Duncan-Ely test: time for standardization.

PMID- 25952691
TI  - Comorbidities and Risk of Complications After Surgery for Esophageal Cancer: A
      Nationwide Cohort Study in Sweden.
AB  - BACKGROUND: The selection for surgery is multifaceted for patients diagnosed with
      esophageal cancer. Since it is uncertain how comorbidity should influence the
      selection, this study addressed comorbidities in relation to risk of severe
      complications following esophageal cancer surgery. METHODS: This population-based
      cohort study was based on prospectively included patients who underwent surgical
      resection for an esophageal or gastro-esophageal junctional cancer in Sweden
      during 2001-2005. The participation rate was 90%. Associations between pre
      defined comorbidities and pre-defined post-operative complications occurring
      within 30 days of surgery were analyzed using multivariable logistic regression.
      The resulting odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted
      for age, sex, tumor stage, tumor histology, neoadjuvant therapy, type of surgery,
      annual hospital volume, other comorbidities, and other complications. RESULTS:
      Among 609 included patients, those with cardiac disease (n = 92) experienced an
      increased risk of pre-defined complications in general (adjusted OR 1.81, 95% CI
      1.13-2.90), while patients with hypertension (n = 137), pulmonary disorders (n =
      79), diabetes (n = 67), and obesity (n = 66) did not. Patients with a Charlson
      comorbidity index score >=2 had substantially increased risks of pre-defined
      complications (adjusted OR 2.44, 95% CI 1.60-3.72). CONCLUSION: Cardiac disease
      and a Charlson comorbidity index score >=2 seem to increase the risk of severe
      and early post-operative complications in patients with esophageal cancer, while
      hypertension, pulmonary disorders, diabetes, and obesity do not. These findings
      should be considered in the clinical decision-making for improved selection of
      patients for surgery.

PMID- 25952697
TI  - Multicomponent cascade reactions of unprotected carbohydrates and amino acids.
AB  - Herein an operationally simple multicomponent reaction of unprotected
      carbohydrates with amino acids and isonitriles is presented. By the extension of
      this Ugi-type reaction to an unprotected disaccharide a novel glycopeptide
      structure was accessible. 

PMID- 25952698
TI  - Decolorization of distillery spent wash effluent by electro oxidation (EC and EF)
      and Fenton processes: A comparative study.
AB  - In this study, laboratory scale experiments were performed to degrade highly
      concentrated organic matter in the form of color in the distillery spent wash
      through batch oxidative methods such as electrocoagulation (EC), electrofenton
      (EF) and Fenton process. The effect of corresponding operating parameters, namely
      initial pH: 2-10; current intensity: 1-5A; electrolysis time: 0.5-4h; agitation
      speed: 100-500rpm; inter-electrode distance: 0.5-4cm and Fenton's reagent dosage:
      5-40mg/L was employed for optimizing the process of spent wash color removal. The
      performance of all the three processes was compared and assessed in terms of
      percentage color removal. For EC, 79% color removal was achieved using iron
      electrodes arranged with 0.5cm of inter-electrode space and at optimum conditions
      of pH 7, 5A current intensity, 300rpm agitation speed and in 2h of electrolysis
      time. In EF, 44% spent wash decolorization was observed using carbon (graphite)
      electrodes with an optimum conditions of 0.5cm inter-electrode distance, pH 3, 4A
      current intensity, 20mg/L FeSO4 and agitation speed of 400rpm for 3h of
      electrolysis time. By Fenton process, 66% decolorization was attained by Fenton
      process at optimized conditions of pH 3, 40mg/L of Fenton's reagent and at 500rpm
      of agitation speed for 4h of treatment time. 

PMID- 25952699
TI  - Study of the natural occurrence of T-2 and HT-2 toxins and their glucosyl
      derivatives from field barley to malt by high-resolution Orbitrap mass
      spectrometry.
AB  - This paper reports a new method for the determination of T-2 and HT-2 toxins and
      their glucosylated derivatives in cereals, and some survey data aimed at
      obtaining more comprehensive information on the co-occurrence of T-2 and HT-2
      toxins and their glucosylated derivatives in naturally contaminated cereal
      samples. For these purposes, barley samples originating from a Northern Italian
      area were analysed by LC-HRMS for the presence of T-2, HT-2 and relevant glucosyl
      derivatives. Quantitative analysis of T-2 and HT-2 glucosides was performed for
      the first time using a recently made available standard of T-2 glucoside. The
      glucosyl derivative of HT-2 was detected at levels up to 163 ug kg(-1) in 17 of
      the 18 analysed unprocessed barley grains, whereas the monoglucosyl derivative of
      T-2 toxin was detected in only a few samples and at low ug kg(-1) levels. The
      ratio between glucosylated toxins (sum of T-2 and HT-2 glucosides) and native
      toxins (sum of T-2 and HT-2) ranged from 2% to 283%. Moreover, taking advantage
      of the possibility of retrospective analysis of full-scan HRMS chromatograms,
      samples were also screened for the presence of other type-A trichothecenes,
      namely neosolaniol, diacetoxyscirpenol and their monoglucosyl derivatives, which
      were detected at trace levels. A subset of nine different samples was subjected
      to micro-maltation in order to carry out a preliminary investigation on the fate
      of T-2, HT-2 and relevant glucosides along the malting process. Mycotoxin
      reduction from cleaned barley to malt was observed at rates ranging from 4% to
      87%.

PMID- 25952700
TI  - Transformation of 17beta-Estradiol by Phanerochaete chrysosporium in Different
      Culture Media.
AB  - The removal of 17beta-estradiol (E2) by white-rot fungus Phanerochaete
      chrysosporium cultured in classic Kirk or potato medium was systematically
      investigated. Results demonstrated that E2 can be efficiently removed regardless
      of culture media type. However, the reaction intermediates and transformation
      pathways varied in different media. Estrone (E1) and estriol (E3) were
      sequentially generated as intermediates in the potato medium, but these
      intermediates were absent in Kirk medium. Such results were found to correlate to
      the peroxidases produced in Kirk medium. These enzymes catalyzed one-electron
      oxidation of E2 to form radicals that can undergo oxidative coupling. Similar
      enzymes were not detected in the potato medium, thus E2 underwent in vitro
      oxidation to form E1 and E3 sequentially. Adding glucose to the potato medium
      further accelerated such processes. The findings in this study provide insights
      into estrogen reactions mediated by P. chrysosporium and for potential
      development of biodegradation methods to reduce estrogen contamination levels. 

PMID- 25952701
TI  - Some pathophysiological insights into ovarian infestation by Myxobolus sp.
      (Myxozoa: Myxosporea) in Clarias gariepinus (Clariids: Silurids) from Benin (West
      Africa).
AB  - Mature female specimens of the catfish Clarias gariepinus originating from Oueme
      River (Benin) were investigated into ovarian myxozoan parasites. Spores of
      Myxobolus sp. (Myxozoa: Myxosporea) were found encrusted in the whitish color
      oocytes which present fat dot aspect in the gonads. The pathological
      investigation by electron microscopy revealed that maturation and multiplication
      of spores induced lytic action, deformation and dysfunction of the oocyte
      internal structures. No host inflammatory reaction was observed, while yolk,
      lipid, mitochondria, and other oocyte components were degenerated inducing empty
      area in the oocyte and could lead to castration in case of wide infestation. The
      mean prevalence was 19.79%. No significant difference was observed within
      seasonal prevalence (chi(2) = 1.771; df = 3; p > 0.05). Though the host length
      classes ranging from 35 to 39 cm and 40 to 45 cm were more infected, difference
      was not significant (chi(2) = 2.273; df = 4; p > 0.05) within them. The spores
      are ovoid in shape with two polar capsules which are equal in size, pyriform, and
      converging in anterior part of spore with four to five polar filament turns.
      Spore body are (11.47 +/- 0.67) * (8.19 +/- 0.52) MUm length by width while polar
      capsule size are (4.24 +/- 0.25) * (3.07 +/- 0.28) MUm and located in the first
      third portion of the spore. The molecular approaches are still running for
      accurate identification of this parasite.

PMID- 25952702
TI  - Twelve myxosporean species of the family Myxobolidae infecting freshwater fishes
      of the River Nile, Egypt, with the description of four novel species.
AB  - Myxosporidian parasites infecting fish are very dangerous parasites causing
      severe damage to a large number of economically important fishes especially in
      aquaculture. A survey of myxosporean parasites infecting four species of fishes
      from the River Nile in Egypt is conducted. One hundred and ninety-five out of 316
      fish specimens with a percentage of 61.7% were found to be naturally infected
      with these parasites. Light microscopic examination of different tissues revealed
      the presence of 12 myxosporean species belonging to the family Myxobolidae. Four
      of the identified species are novel and the other eight species are redescribed.
      Myxidium sp.nov. a coelozoic species inhabiting the gallbladder of Labeo
      niloticus with its mature spores float free in bile was detected. These spores
      possess a fusiform, straight, or slightly crescentic shape with less pointed ends
      and two equal polar capsules. Three novel histozoic Myxobolus species infecting
      Oreochromis niloticus were identified. Myxobolus sp(1).nov. is a species
      inhabiting kidney tissue with ovoid spores exhibiting a small intercapsular
      appendix. Myxobolus sp(2).nov. and Myxobolus sp(3).nov. recovered from kidney and
      intestinal tissues. Spores of Myxobolus sp(2).nov. are elliptical in shape with
      an anterior end wider than posterior one. Their two polar capsules are ovoid to
      pyriform occupied nearly the first third of the spore body. Spores of Myxobolus
      sp(3).nov. are broader than long with nearly rounded or ovoid two polar capsules.
      Eight species of the recovered myxosporean parasites are redescribed, Myxobolus
      niloticus Fahmy et al., 1971 from pectoral, dorsal, and tail fins of L.
      niloticus, Henneguya suprabranchiae Landsberg, 1987, and Henneguya branchialis
      Ashmawy et al., 1989 are recovered from the gills and suprabranchial organ of the
      catfish Clarias gariepinus, respectively, Myxobolus naffari Abdel-Ghaffar et al.,
      1998 and Myxobolus imami Ali et al., 2002 are found in the kidney of Barbus bynni
      and L. niloticus, Myxobolus caudatus Ali et al. & Parasitol Res (2002) from Tail
      fin of B. bynni, Myxobolus fomenai Abdel-Ghaffar et al., 2008 from kidney and
      intestinal tissues of O. niloticus, Thelohanellus niloticus Abdel-Ghaffar et al.,
      2012 are observed in the gills of L. niloticus.

PMID- 25952703
TI  - Reproduction barrier between two lineages of bed bug (Cimex lectularius)
      (Heteroptera: Cimicidae).
AB  - Populations of bed bugs, Cimex lectularius, have increased in recent years
      spreading into numerous urban areas across the Western world and making them an
      increasingly important pest of the twenty-first century. Research into
      hybridization within and between different lineages of bed bugs can help us to
      understand processes of micro- and macro-evolution in these ectoparasites and may
      inform the control of this pest species. Hybridization experiments between two
      host lineages of bed bug (C. lectularius) from Central Europe (Czech Republic),
      those associated with humans and those with bats, were conducted under laboratory
      conditions. Number of eggs and early instars were compared between crosses of
      mixed host lineages (interspecific mating) with pairs from the same host lineage,
      those from the same locality and same lineage from different localities
      (intraspecific mating). While crosses within host lineages resulted in egg
      production and later instars, crosses between different host lineages were
      unsuccessful, although of the mated females possessed sperm in their
      mesospermaleges and/or seminal conceptacles. These crosses did not even result in
      egg production. Moreover, in the mixed lineage crosses, mortality rates in adults
      were higher (51 and 50% higher in bat and human lineage, respectively) than in
      those animals from the same lineage. Survival of adults was in pairs from the
      same locality slightly higher than in pairs from different localities and
      differed statistically. These results support the existence of post-mating
      barriers and show reproductive isolation between two lineages of C. lectularius.
      Bat and human host adaptations can promote evolving of such barriers and can be
      product of alloxenic speciation.

PMID- 25952705
TI  - Length of tick repellency depends on formulation of the repellent compound
      (icaridin = Saltidin(r)): tests on Ixodes persulcatus and Ixodes ricinus placed
      on hands and clothes.
AB  - The present study had the aim to test the repellent potential of the compound
      icaridin = Saltidin(r) against the tick species Ixodes ricinus and Ixodes
      persulcatus using different formulations of the compound. Tests were done on
      backs of impregnated human hands, on impregnated linen cloth and versus
      impregnated dog hair. It was found that 1. Ixodes persulcatus-the common Eastern
      European, Russian Ixodes species is significantly sensitive to icaridin =
      Saltidin(r) as I. ricinus protecting for the test period of 5 h. This is an
      important finding, since I. persulcatus is the vector of agents of the severe
      Eastern meningoencephalitis; 2. that this repellent compound acts similarly on
      both I. ricinus and I. persulcatus, when sprayed either on naked skin or on
      cloths; 3. that there are only slight differences in duration of the repellency
      when using different formulations containing icaridin = Saltidin(r); 4. that
      icaridin = Saltidin(r) sprayed on dog hair has identical repellent effects like
      those seen on human skin and cloths; thus, this compound can also be used to
      protect animals such as dogs, cats, horses; and 5. that the icaridin =
      Saltidin(r) did not induce a bad sensation on skin, nor bad smells; furthermore,
      it was not sticky and did not leave residuals neither on clothes nor on dog's
      hair.

PMID- 25952704
TI  - Acetylcholinesterase 1 in populations of organophosphate-resistant North American
      strains of the cattle tick, Rhipicephalus microplus (Acari: Ixodidae).
AB  - Rhipicephalus microplus, the cattle fever tick, is a global economic problem to
      the cattle industry due to direct infestation of cattle and pathogens transmitted
      during feeding. Cattle fever tick outbreaks continue to occur along the Mexico-US
      border even though the tick has been eradicated from the USA. The organophosphate
      (OP) coumaphos targets acetylcholinesterase (AChE) and is the approved acaricide
      for eradicating cattle fever tick outbreaks. There is evidence for coumaphos
      resistance developing in cattle ticks in Mexico, and OP-resistant R. microplus
      ticks were discovered in outbreak populations of Texas in 2005. The molecular
      basis of coumaphos resistance is not known, and our study was established to
      gather further information on whether AChE1 is involved in the resistance
      mechanism. We also sought information on allele diversity in tick populations
      with different levels of coumaphos resistance. The overarching project goal was
      to define OP resistance-associated gene mutations such that a DNA-based
      diagnostic assay could be developed to assist the management of resistance. Three
      different AChE transcripts have been reported in R. microplus, and supporting
      genomic and transcriptomic data are available at CattleTickBase. Here, we report
      the complete R. microplus AChE1 gene ascertained by sequencing a bacterial
      artificial chromosome clone containing the entire coding region and the flanking
      5' and 3' regions. We also report AChE1 sequences of larval ticks from R.
      microplus strains having different sensitivities to OP. To accomplish this, we
      sequenced a 669-bp region of the AChE1 gene corresponding to a 223 amino acid
      region of exon 2 to assess alleles in seven strains of R. microplus with varying
      OP resistance phenotypes. We identified 72 AChE1 sequence variants, 2 of which
      are strongly associated with OP-resistant phenotypes. Esterase-like sequences
      from the R. microplus transcriptome RmiTr Version 1.0 were compared to the
      available sequence databases to identify other transcripts with similarity to
      AChE1. 

PMID- 25952706
TI  - Ac45 silencing mediated by AAV-sh-Ac45-RNAi prevents both bone loss and
      inflammation caused by periodontitis.
AB  - AIM: Periodontitis induced by oral pathogens leads to severe periodontal tissue
      damage and osteoclast-mediated bone resorption caused by inflammation. On the
      basis of the importance of Ac45 in osteoclast formation and function, we
      performed this study to evaluate the therapeutic potential of periodontitis by
      local adeno-associated virus (AAV)-mediated Ac45 gene knockdown. MATERIAL AND
      METHODS: We used AAV-mediated short hairpin RNAi knockdown of Ac45 gene
      expression (AAV-sh-Ac45) to inhibit bone erosion and gingival inflammation
      simultaneously in a well-established periodontitis mouse model induced by
      Porphyromonas gingivalis W50. Histological studies were performed to evaluate the
      bone protection of AAV-sh-Ac45. Immunochemistry, ELISA and qRT-PCR were performed
      to reveal the role of Ac45 knockdown on inflammation, immune response and
      expression of cytokine. RESULTS: We found that Ac45 knockdown impaired osteoclast
      mediated extracellular acidification and bone resorption in vitro and in vivo.
      Furthermore, local administration of AAV-sh-Ac45 protected mice from bone erosion
      by >85% and attenuated inflammation and decreased infiltration of T cells,
      dendritic cells and macrophages in the periodontal lesion. Notably, the
      expression of pro-inflammatory cytokines was also reduced. CONCLUSIONS: Local AAV
      sh-Ac45 gene therapy efficiently protects against periodontal tissue damage and
      bone erosion through both inhibition of osteoclast function and attenuating
      inflammation, and may represent a powerful new treatment strategy for
      periodontitis.

PMID- 25952708
TI  - A 10-YEAR HOSPITAL-BASED HEALTH TECHNOLOGY ASSESSMENT PROGRAM IN A PUBLIC
      HOSPITAL IN ARGENTINA.
AB  - OBJECTIVES: To describe the first hospital-based health technology assessment
      (HTA) program in a public hospital in Argentina, and report some clinical,
      educational, economic and organizational results after 10 years of its
      implementation. METHODS: A hospital-based HTA program was created in March 2001
      at Hospital Garrahan (Buenos Aires, Argentina), a national pediatric facility
      with a self-managed budget. Its main goal is to promote a rational and evidence
      based technologic development. The program consists of HTA reports for technology
      acquisition, clinical practice guidelines (CPG), capacity building in research
      and management, and technical support for health services research (HSR). The
      evaluation cycle comprises: prioritization, evidence synthesis, dissemination and
      monitoring. We report program performance, comment educational and organizational
      effects, and discuss unresolved issues and future challenges. RESULTS: During the
      first 10 years the program produced 18 HTA reports on drugs (6 = 33 percent),
      therapeutic (6 = 33 percent), preventive (2 = 11 percent) or diagnostic (2 = 11
      percent) procedures and institutional programs (3 = 17 percent). The scope
      covered effectiveness (12 = 67 percent), safety (10 = 56 percent), budget impact
      (6 = 33 percent), cost-effectiveness (2 = 11 percent) and organizational impact
      (3 = 17 percent). Mean time from request to report was 10 months. Eleven
      pediatric CPGs were submitted to expert consensus and disseminated for full-text
      Web access. A 1-year course on research and management was completed by 225
      professionals in 6 years, and twenty-two projects for HSR were coached.
      CONCLUSIONS: Our experience shows that an HTA program is both feasible and useful
      in a public hospital of a developing country. Promotion of hospital-based HTA,
      professional integration in HTA activities and network collaboration to discuss
      unresolved issues with colleagues can multiply the benefits and optimize the use
      of hospital budgets.

PMID- 25952709
TI  - Unplanned return to theater: A quality of care and risk management index?
AB  - INTRODUCTION: Surgical quality and risk management is a major public health
      issue. The consequences of unplanned return to theater are social, occupational,
      financial and even legal. Unscheduled revision surgery is a major adverse event,
      resulting from serious complications - some of which are thought to be avoidable.
      The present study sought to assess and analyze the incidence of unplanned return
      to theater in an orthopedic surgery department. The study hypothesis was that
      some of the complications involved could be avoided. PATIENTS AND METHOD: A mixed
      retrospective-prospective study examined a consecutive series of 10,158 patients
      operated on in an orthopedic and traumatologic surgery department between January
      2011 and December 2013. Patients undergoing revision surgery for reasons directly
      related to the primary procedure were analyzed. Patients were distributed among
      the following subgroups: infection, implant dislocation; hemorrhagic
      complication, mechanical complication, problem of primary technique, stiffness,
      wound healing disorder. Specific indicators of dysfunction liable to have
      contributed to onset of the complication were applied in each subgroup, to
      determine the avoidable or unavoidable nature of the event. RESULTS: Two hundred
      and twenty-four patients (2.2%) underwent revision surgery for reasons directly
      related to the primary procedure. One hundred and eight cases (48.2%) were
      considered to have been avoidable: 48 infections (21.4%), 27 implant dislocations
      (12%), 15 hemorrhagic complications (6.7%), 66 mechanical complications (29.5%),
      35 technical problems at primary surgery (15.6%), 21 cases of stiffness (9.3%),
      and 12 cases of delayed wound healing (5.3%). Mean time to revision surgery was
      2.7 +/- 2.6 months. Extending the time-window to 1 year recruited extra cases: in
      31.7% of cases, onset was after the 90th postoperative day, which is the usual
      deadline. The rate of unplanned return to theater was higher after unscheduled
      (traumatic: 3.2%) than scheduled surgery (1.7%, P < 0.001). CONCLUSION: Return to
      surgery in orthopedic and traumatologic surgery is underestimated. Annual
      incidence was 2.2%, and twice as high (3.2%) following traumatologic compared to
      scheduled surgery (1.7%). Analysis found that almost half the cases were
      avoidable. They represent a relevant and easily assessed indicator of treatment
      quality and associated risk management. A national or even international database
      in the form of an anonymous registry of revision surgeries would be useful.

PMID- 25952710
TI  - Long-term outcomes of primary constrained condylar knee arthroplasty.
AB  - BACKGROUND: Although constrained condylar knee (CCK) inserts are widely used for
      total knee arthroplasty (TKA), their long-term outcomes remain unclear. We sought
      to evaluate patients with at least 10 years' follow-up after CCK TKA to identify
      potential adverse events (osteolysis, loosening, constraint-mechanism failure),
      assess functional outcomes with special emphasis on range of motion, and
      determine prosthesis survival. HYPOTHESIS: Increasing constraint by implantation
      of a CCK insert does not increase the long-term frequencies of osteolysis or
      mechanical loosening. MATERIAL AND METHODS: We studied 43 knees after Legacy((r))
      CCK TKA. The indication was severe deformity (n=20), pre-operative laxity (n=6),
      or failure to achieve intra-operative balancing (n=17). There were 41 patients
      with a mean age of 66 years (21-88). A history of one or more surgical procedures
      was noted for 27 (63%) knees. Outcome measures were the Hospital for Special
      Surgery (HSS) knee score, Knee Society Score (KSS), and change in the hip-knee
      ankle (HKA) angle. Prosthesis survival was assessed using revision surgery for
      any reason or for reasons other than infection as the censoring criterion.
      RESULTS: Complications other than venous thrombosis occurred in 16% of patients,
      including 3 who required revision surgery (septic loosening, n=2; and major
      instability in a patient with ipsilateral hip arthrodesis). No cases of
      osteolysis or aseptic loosening were recorded. Mean follow-up was 12.7 years
      (range, 10-14). At last follow-up, the HSS score had improved from 53 (26-83) pre
      operatively to 80 (55-93), the KSS knee component from 42 (16-77) to 90 (77-99),
      and the KSS function component from 31 (0-80) to 61 (10-90) (P<0.001). Mean range
      of flexion increased from 109 degrees  (50 degrees -140 degrees ) to 112 degrees 
      (90 degrees -130 degrees ) (P=0.12). The HKA angle changed from 182 degrees +/
      15.5 degrees  (150 degrees -210 degrees ) to 179.5 degrees +/-2.5 degrees  (174
      degrees -184 degrees ) (P=0.5). The 11-year prosthesis survival rate was 88.5%
      (95% confidence interval, 0.69-0.94) overall and 97.7% (0.76-0.99) after
      excluding the cases of infection. DISCUSSION: Long-term functional gains after
      CCK TKA were similar to those reported after standard posterior-stabilised TKA,
      with no cases of constraint-mechanism failure or osteolysis. The complication
      rate was higher, with decreased survival compared to standard TKA, but the knee
      deformities and/or instability were particularly severe and two-thirds of knees
      had a history of one or more surgical procedures.

PMID- 25952707
TI  - Sexually Transmitted Infection History among Adolescents Presenting to the
      Emergency Department.
AB  - BACKGROUND: Adolescents and young adults account for about half of the annual
      diagnoses of sexually transmitted infections (STI) in the United States.
      Screening and treatment for STIs, as well as prevention, are needed in health
      care settings to help offset the costs of untreated STIs. OBJECTIVE: Our aim was
      to evaluate the prevalence and correlates of self-reported STI history among
      adolescents presenting to an emergency department (ED). METHODS: Over two and a
      half years, 4389 youth (aged 14-20 years) presenting to the ED completed
      screening measures for a randomized controlled trial. About half (56%) reported
      lifetime sexual intercourse and were included in analyses examining sexual risk
      behaviors (e.g., inconsistent condom use), and relationships of STI history with
      demographics (sex, age, race, school enrollment), reason for ED presentation
      (i.e., medical or injury), and substance use. RESULTS: Among sexually active
      youth, 10% reported that a medical professional had ever told them they had an
      STI (212 females, 35 males). Using logistic regression, female sex, older age,
      non-Caucasian race, not being enrolled in school, medically related ED chief
      complaint, and inconsistent condom use were associated with increased odds of
      self-reported STI history. CONCLUSIONS: One in 10 sexually active youth in the ED
      reported a prior diagnosed STI. Previous STI was significantly higher among
      females than males. ED providers inquiring about inconsistent condom use and
      previous STI among male and female adolescents may be one strategy to focus
      biological testing resources and improve screening for current STI.

PMID- 25952711
TI  - Innovative uses of technology in online midwifery education.
AB  - Women's health care in the United States is at a critical juncture. There is
      increased demand for primary care providers, including women's health specialists
      such as certified nurse-midwives/certified midwives, women's health nurse
      practitioners, and obstetrician-gynecologists, yet shortages in numbers of these
      providers are expected. This deficit in the number of women's health care
      providers could have adverse consequences for women and their newborns when women
      have to travel long distances to access maternity health care. Online education
      using innovative technologies and evidence-based teaching and learning strategies
      have the potential to increase the number of health care providers in several
      disciplines, including midwifery. This article reviews 3 innovative uses of
      online platforms for midwifery education: virtual classrooms, unfolding case
      studies, and online return demonstrations of clinical skills. These examples of
      innovative teaching strategies can promote critical and creative thinking and
      enhance competence in skills. Their use in online education can help enhance the
      student experience. More students, including those who live in rural and
      underserved regions and who otherwise might be unable to attend a traditional
      onsite campus, are provided the opportunity to complete quality midwifery
      education through online programs, which in turn may help expand the women's
      health care provider workforce. This article is part of a special series of
      articles that address midwifery innovations in clinical practice, education,
      interprofessional collaboration, health policy, and global health. 

PMID- 25952712
TI  - Morphologic differences observed by scanning electron microscopy according to the
      reason for pseudophakic IOL explantation.
AB  - PURPOSE: To compare variations in surface morphology, as studied by scanning
      electron microscopy (SEM), of explanted intraocular lenses (IOLs) concerning the
      cause leading to the explantation surgery. METHODS: In this prospective
      multicenter study, explanted IOLs were analyzed by SEM and energy-dispersive X
      ray spectroscopy. The IOLs were explanted in the centers of the research group
      from 2006 to 2012. The primary procedure was phacoemulsification in all cases.
      RESULTS: The study evaluated 40 IOLs. The main causes for explantation were IOL
      dislocation, refractive error, and IOL opacification. Those explanted due to
      dislocation demonstrated calcifications in 8 lenses (50%), salt precipitates in 6
      cases (37.5%), and erythrocytes and fibrosis/fibroblasts in 2 cases (12.5%). In
      the refractive error cases, the SEM showed proteins in 5 cases (45.5%) and salt
      precipitates in 4 lenses (36.4%). In IOL opacification, the findings were
      calcifications in 2 of the 3 lenses (66.6%) and proteins in 2 lenses (66.6%).
      CONCLUSIONS: A marked variation in surface changes was observed by SEM. Findings
      did not correlate with cause for explantation. Scanning electron microscopy is a
      useful tool that provides exclusive information regarding the IOL biotolerance
      and its interactions with surrounding tissues.

PMID- 25952713
TI  - Normative data for macular volume with high-definition spectral-domain optical
      coherence tomography (Spectralis).
AB  - PURPOSE: To establish normative data for macular volume by spectral-domain
      optical coherence tomography (SD-OCT) in subjects with no known retinal disease.
      METHODS: In an academic institutional setting, 50 subjects (age range 20-84
      years) with no known retinal disease, best-corrected visual acuity 20/20, and
      normal intraocular pressure were enrolled. The subjects were divided into 3 age
      groups: group 1 included subjects 20-40 years of age, group 2 included subjects
      41-60 years of age, and group 3 included subjects 61 years of age and older. All
      subjects underwent a complete ophthalmologic examination and testing, if needed,
      to rule out any retinal diseases or glaucoma. Retinal volume (RV) in 9 Early
      Treatment Diabetic Retinopathy Study (ETDRS) subfields and total macular volume
      (TMV) inclusive of all 9 subfields were analyzed. Statistical analyses were
      carried out using analysis of variance. RESULTS: Overall, the mean TMV +/- SD for
      ETDRS circles with a diameter of 1, 2.22, and 3.45 mm was determined to be 3.04
      +/- 0.14 mm3. Among the ETDRS subfields, RV was highest in the nasal outer field,
      with a mean of 0.47 +/- 0.02 mm3. The TMV did not show a significant difference
      with age (p = 0.17). However, TMV was significantly higher in males (p = 0.003)
      and in Caucasian and Asian subjects compared to African Americans (p = 0.017).
      CONCLUSIONS: Normative values for total macular volume in ETDRS subfields in
      otherwise healthy eyes were measured to be 3.04 +/- 0.14 mm3.

PMID- 25952714
TI  - CYP1B1 gene analysis and phenotypic correlation in Portuguese children with
      primary congenital glaucoma.
AB  - PURPOSE: To investigate the prevalence of CYP1B1 mutations in Portuguese children
      with primary congenital glaucoma (PCG) and to study the possible correlations
      between the mutation status and clinical features of the disease. METHODS: DNA
      sequencing analysis of the CYP1B1 gene was used to screen 21 children with PCG
      followed on Paediatric Ophthalmology and Medical Genetics consultations at D.
      Estefania's Hospital (Centro Hospitalar de Lisboa Central, Portugal). The effect
      of mutations on the phenotype of the patients was also assessed. Presence and
      type of mutations in CYP1B1 gene, age at diagnosis, bilaterality, age at first
      surgery, postoperative intraocular pressure and corneal diameter, final visual
      acuity, number of surgical reinterventions, and number of antiglaucoma
      medications required postoperatively were noted. RESULTS: Mutations in the CYP1B1
      gene in 6 patients (28.57%) were detected, all compound heterozygotes. Seven
      types of mutations were identified: c.182G>A, c.317C>A, c.535delG,
      c.1064_1076del, c.1159G>A, c.1310C>T, and c.1390dupT. All patients with these
      mutations developed bilateral PCG, whereas in the group without mutations only 7
      (46.67%) showed bilateral disease. Age at diagnosis was lower in the group of
      patients with these mutations (0.0 +/- 0.00 vs 4.5 +/- 2.63 months, p<0.01). In
      the remaining variables (age at first surgery, postoperative intraocular pressure
      and corneal diameter, final visual acuity, number of surgical reinterventions and
      antiglaucoma medications required postoperatively), no significant differences
      between the groups were detected (p>0.05 for all comparisons). CONCLUSIONS: This
      study is the first to report the variety of mutations in the CYP1B1 gene in a
      group of Portuguese children with PCG and to describe 2 new mutations. Genetic
      analysis of PCG must be carried out, although it has not yet been possible to
      establish a genotype-phenotype correlation, with the exception of bilaterality
      and early age at diagnosis.

PMID- 25952715
TI  - Hydropolish: a controlled trial on a technique to eradicate residual cortical
      lens fibers in phacoemulsification cataract surgery.
AB  - PURPOSE: To assess the efficacy and safety of a noncontact, fluid-based capsular
      polishing technique (hydropolish) to remove residual cortical fibers (RCFs) and
      epithelial cells from the posterior and equatorial capsule in phacoemulsification
      cataract surgery. METHODS: Hydropolish involved manual irrigation of the
      posterior and equatorial capsule after irrigation/aspiration, using a 27-G
      hydrodissection cannula. This prospective, consecutive, single surgeon controlled
      trial was conducted at a dedicated ophthalmic surgery center in Sydney,
      Australia, between December 20, 2006, and July 14, 2010. Single eyes of
      consecutive patients underwent cataract surgery without use of hydropolish
      (control group), while those on or after July 21, 2010, underwent hydropolish
      (intervention group). Corrected distance visual acuity (CDVA) up to 1 month
      postoperatively, surgical complications, and hydropolish time were documented.
      RESULTS: A total of 1531 eyes were included in this study (hydropolish n = 682;
      control n = 849). After adjusting for age, sex, and nuclear sclerosis grade, no
      significant difference was found between hydropolish and control groups when
      preoperative CDVA was compared against postoperative CDVA at 1 day, 1 week, and 1
      month (p>0.05). CONCLUSIONS: Hydropolish is a rapid and safe technique that can
      remove RCFs from the posterior and equatorial capsule in phacoemulsification
      cataract surgery. It does not compromise postoperative CDVA.

PMID- 25952716
TI  - Comparative imaging of European eels (Anguilla anguilla) for the evaluation of
      swimbladder nematode (Anguillicoloides crassus) infestation.
AB  - This study compares diagnostic imaging tools in detecting the parasitic
      swimbladder nematode Anguillicoloides crassus in Anguilla anguilla (L.) and
      focuses on ultrasound in an attempt to develop a non-destructive, field
      diagnostic test. Ultrasound use could allow the parasite to be diagnosed without
      decreasing the number of critically endangered European eels through post-mortem.
      In the preliminary study, eels were examined with computed radiography, computed
      tomography, magnetic resonance imaging, 14 MHz high-end ultrasound and 5 MHz low
      end portable ultrasound, and the results were compared with post-mortem findings.
      This ultrasound scanning technique did not produce any promising results. A
      second batch of eels was examined using the same high-end and low-end
      ultrasounds, but employing a different scanning technique and comparing the
      results with post-mortem. This second study, scanning along the midline from
      below, allowed for the detection of anomalies associated with moderately infected
      animals. None of the eels used in this study were severely infected; thus, no
      conclusions can be made regarding the use of ultrasound in those animals.
      Overall, it was found that none of the techniques were useful in diagnosing
      mildly infected individuals; therefore, no single diagnostic imaging tool is
      sensitive enough to replace post-mortem for definite diagnosis. 

PMID- 25952717
TI  - Talofibular Bony Impingement in the Ankle.
AB  - BACKGROUND: Talofibular bony impingement has not previously been reported, since
      it is difficult to detect on plain radiograph, similar to the spur on the
      anterior border of the medial malleolus and anterior portion of the medial talar
      facet. We hypothesized that talofibular bony impingement can cause limited
      dorsiflexion of the ankle. The aim of this study was to evaluate talofibular bony
      impingement as a distinct form of impingement that limits dorsiflexion of the
      ankle. METHODS: This study included 20 consecutive patients (21 ankles) with
      talofibular impingement and 19 consecutive patients (19 ankles) with lateral
      ankle instability without talofibular impingement. Presence or absence of
      talofibular impingement was confirmed under direct intraoperative visualization.
      Dorsiflexion before and after excision of the impinging spurs was measured.
      Findings on plain radiographs and computed tomography were compared between the
      groups. Pre- and postoperative clinical assessments were done with Foot Function
      Index, visual analog scale for pain, and American Orthopaedic Foot & Ankle
      Society ankle-hindfoot score at a mean follow-up of 1.4 years. RESULTS: After
      removal of the bony impingement, the range of dorsiflexion increased by a mean
      7.9 degrees (range, 2.5 to 11.0 degrees) in the impingement group. The mean
      distance between the fibula and lateral process of the talus on weight- bearing
      anteroposterior radiograph of the ankle was 1.2 mm (range, 0 to 4.5) in the
      impingement group and 3.2 mm (range, 1 to 4.5) in the control group. On axial
      computed tomography image, bony protrusion of the lateral process of the talus
      was frequently present in the impingement group, and the mean amount of
      protrusion was more than that of the control group. Clinical findings improved
      overall. CONCLUSIONS: Talofibular impingement was a cause of limited
      dorsiflexion, and the diagnosis was confirmed intraoperatively. LEVEL OF
      EVIDENCE: Level III, retrospective comparative study.

PMID- 25952718
TI  - Necrosis of the nipple-areola complex in breast reduction. Our personal way to
      solve problem.
AB  - Necrosis of the NAC is a condition that penalizes patients who underwent breast
      reduction surgery or mastopexy. Breast reduction is a widely used technique for
      over-sized breasts. Breast hypertrophy, in fact, can cause the onset of many
      issues--both aesthetical and pathological--because of the excessive weight that
      the breasts exert on the patient's spine. Aim and objective of our study is to
      suggest a systematic use of diagnostic imaging composed of pre-operative and
      intraoperative ultrasound with color-Doppler and pre-operative MRI. Trying to
      solve this problem definitively, we relied on our notions of anatomy on ten fresh
      cadavers, on whose twenty breasts we could make very detailed dissections. The
      dissections led us to conclude that, albeit with their anatomic differences, each
      breast was characterized by a vascular-nervous pedicle coming out from the inter
      costal spaces and aimed to the blood supply to the NAC. To overcome the anatomic
      variations between one subject and another--but also between one breast and the
      other from the same patient, we relied on diagnostic imaging, both in the pre
      operative and in the intra-operative staging. This way we were able to intervene
      successfully with 15 patients, none of which has complained damages to the
      vascularity or innervation of the NAC so far. In conclusion we believe that pre
      and intra operative diagnostic imaging is the only way to completely eliminate
      any potential risk of NAC necrosis. Only by means of the systematic use of
      conventional imaging--especially during surgery--it is possible to constantly
      monitor the position of the NAC's pedicle in a breast that is being reduced in
      volume.

PMID- 25952719
TI  - Self-training in significance space of support vectors for imbalanced biomedical
      event data.
AB  - BACKGROUND: Pairwise relationships extracted from biomedical literature are
      insufficient in formulating biomolecular interactions. Extraction of complex
      relations (namely, biomedical events) has become the main focus of the text
      mining community. However, there are two critical issues that are seldom dealt
      with by existing systems. First, an annotated corpus for training a prediction
      model is highly imbalanced. Second, supervised models trained on only a single
      annotated corpus can limit system performance. Fortunately, there is a large pool
      of unlabeled data containing much of the domain background that one can exploit.
      RESULTS: In this study, we develop a new semi-supervised learning method to
      address the issues outlined above. The proposed algorithm efficiently exploits
      the unlabeled data to leverage system performance. We furthermore extend our
      algorithm to a two-phase learning framework. The first phase balances the
      training data for initial model induction. The second phase incorporates domain
      knowledge into the event extraction model. The effectiveness of our method is
      evaluated on the Genia event extraction corpus and a PubMed document pool. Our
      method can identify a small subset of the majority class, which is sufficient for
      building a well-generalized prediction model. It outperforms the traditional self
      training algorithm in terms of f-measure. Our model, based on the training data
      and the unlabeled data pool, achieves comparable performance to the state-of-the
      art systems that are trained on a larger annotated set consisting of training and
      evaluation data.

PMID- 25952721
TI  - Continuous and dynamic spectral tuning of single nanowire lasers with
      subnanometer resolution using hydrostatic pressure.
AB  - We report continuous, dynamic, reversible, and widely tunable lasing from 367 to
      337 nm from single GaN nanowires (NWs) by applying hydrostatic pressure up to ~7
      GPa. The GaN NW lasers, with heights of 4-5 MUm and diameters ~140 nm, are
      fabricated using a lithographically defined two-step top-down technique. The
      wavelength tuning is caused by an increasing Gamma direct bandgap of GaN with
      increasing pressure and is precisely controllable to subnanometer resolution. The
      observed pressure coefficients of the NWs are ~40% larger compared with GaN
      microstructures fabricated from the same material or from reported bulk GaN
      values, revealing a nanoscale-related effect that significantly enhances the
      tuning range using this approach. This approach can be generally applied to other
      semiconductor NW lasers to potentially achieve full spectral coverage from the UV
      to IR. 

PMID- 25952720
TI  - Exposure to organophosphate and polybrominated diphenyl ether flame retardants
      via indoor dust and childhood asthma.
AB  - Although the ubiquitous detection of polybrominated diphenyl ether (PBDE) and
      organophosphate flame retardants (PFRs) in indoor dust has raised health
      concerns, only very few epidemiological studies have assessed their impact on
      human health. Inhalation of dust is one of the exposure routes of FRs, especially
      in children and can be hazardous for the respiratory health. Moreover, PFRs are
      structurally similar to organophosphate pesticides, which have been associated
      with allergic asthma. Thus, we investigated whether the concentrations of PFRs
      and PBDEs in indoor dust are associated with the development of childhood asthma.
      We selected 110 children who developed asthma at 4 or at 8 years old and 110
      matched controls from a large prospective birth cohort (BAMSE - Barn, Allergy,
      Milieu Stockholm Epidemiology). We analyzed the concentrations of 7 PFRs and 21
      PBDEs in dust collected around 2 months after birth from the mother's mattress.
      The abundance rank in dust was as follows: TBOEP?TPHP>mmp
      TMPP>EHDPHP~TDCIPP>TCEP~TCIPP~BDE-209?BDE-99>BDE-47>BDE-153>BDE-183>BDE-100.
      There was no positive association between the FRs in mattress dust and the
      development of childhood asthma. In contrast, dust collected from mattresses of
      the mothers of children who would develop asthma contained significant lower
      levels of TPHP and mmp-TMPP. This study provides data on a wide range of PFRs and
      PBDEs in dust samples and development of asthma in children.

PMID- 25952722
TI  - Serological examination of fattening pigs reveals associations between Ascaris
      suum, lung pathogens and technical performance parameters.
AB  - Diagnosing the presence of the highly prevalent and economically important pig
      parasite Ascaris suum on fattening farms has so far been challenging. Currently,
      only the number of livers affected at slaughter is routinely used to measure
      parasite exposure. However, recently, a new serological test was developed based
      on the detection of antibodies to the A. suum haemoglobin molecule. The test
      showed to be highly sensitive for the detection of exposure to A. suum in
      fattening pigs. In this study we first compared the performance of A. suum
      serology versus the percentage of affected livers at slaughter, subsequently we
      investigated potential associations between A. suum infection levels and exposure
      to important lung pathogens and finally we identified correlations between
      serological data and technical performance parameters (TPIs) from 20 Belgian and
      20 German pig fattening farms. In both Belgian and German farms, a significant
      relationship was detected between elevated average Ascaris serology and
      percentages of affected livers (rho=0.63 and rho=0.75, respectively). On the
      Belgian farms, both Ascaris serology and the percentage of affected livers were
      negatively correlated with average daily gain (ADG) (rho=-0.69 and rho=-0.56,
      respectively). Using the German dataset, only a borderline negative association
      was detected between the percentage of affected livers and the ADG (rho=-0.44,
      P=0.053). In contrast, only in the German farms, correlations between the
      percentage of affected lungs at slaughter and elevated presence of A. suum and
      several other airway pathogens were detected. To conclude, this study indicates
      that serological screening for A. suum on fattening farms is an attractive new
      diagnostic tool that can be used to indicate the presence of roundworm infection
      by measuring infection intensity. Furthermore the results of this study also add
      weight to the evidence that both roundworm infections as well as herd exposure to
      airway pathogens have a significant impact on farm productivity and hence, that
      all these factors should to be taken into account when assessing pig health and
      farm productivity. 

PMID- 25952723
TI  - [Paternal GNAS mutations: Which phenotypes? What genetic counseling?].
AB  - Parental imprinting and the type of the genetic alteration play a determinant
      role in the phenotype expression of GNAS locus associated to
      pseudohypoparathyroidism (PHP). GNAS locus gives rise to several different
      messenger RNA transcripts that are derived from the paternal allele, the maternal
      allele, or both and can be either coding or non-coding. As a consequence, GNAS
      mutations lead to a wide spectrum of phenotypes. An alteration in the coding
      sequence of the gene leads to a haplo-insufficiency and a dysmorphic phenotype
      (Albright's syndrome or AHO). AHO is a clinical syndrome defined by specific
      physical features including short stature, obesity, round-shaped face,
      subcutaneous ossifications, brachymetarcapy (mainly of the 4th and 5th ray). If
      the alteration is on the maternal allele, there is a hormonal resistance to the
      PTH at the kidney level and to the TSH at the thyroid level. The phenotype is
      known as pseudohypoparathyroidism type 1a (PHP1a). If the alteration is on the
      paternal allele, there are few clinical signs with no hormonal resistance and the
      phenotype is known as pseudopseudo hypoparathyroidism (pseudo-PPHP). Heterozygous
      GNAS mutations on the paternal GNAS allele were associated with intra uterin
      growth retardation (IUGR). Moreover, birth weights were lower with paternal GNAS
      mutations affecting exon 2-13 than with exon 1/intron 1 mutations suggesting a
      role for loss of function XLalphas. Progressive osseous heteroplasia (POH) is a
      rare disease of ectopic bone formation, characterized by cutaneous and
      subcutaneous ossifications progressing towards deep connective and muscular
      tissues. POH is caused by a heterozygous GNAS inactivating mutation and has been
      associated with paternal inheritance. However, genotype/phenotype correlations
      suggest that there is no direct correlation between the ossifying process and
      parental origin, as there is high variability in heterotopic ossification.
      Clinical heterogeneity makes genetic counseling a very delicate matter,
      specifically where paternal inheritance is concerned as it can lead either to a
      mild expression of pseudo-PHP or to a severe one of POH. 

PMID- 25952724
TI  - Plasmodium falciparum antioxidant protein reveals a novel mechanism for balancing
      turnover and inactivation of peroxiredoxins.
AB  - Life under aerobic conditions has shaped peroxiredoxins (Prx) as ubiquitous thiol
      dependent hydroperoxidases and redox sensors. Structural features that balance
      the catalytically active or inactive redox states of Prx, and, therefore, their
      hydroperoxidase or sensor function, have so far been analyzed predominantly for
      Prx1-type enzymes. Here we identify and characterize two modulatory residues of
      the Prx5-type model enzyme PfAOP from the malaria parasite Plasmodium falciparum.
      Gain- and loss-of-function mutants reveal a correlation between the enzyme
      parameters and the inactivation susceptibility of PfAOP with the size of residue
      109 and the presence or absence of a catalytically relevant but nonessential
      cysteine residue. Based on our kinetic data and the crystal structure of
      PfAOP(L109M), we suggest a novel mechanism for balancing the hydroperoxidase
      activity and inactivation susceptibility of Prx5-type enzymes. Our study provides
      unexpected insights into Prx structure-function relationships and contributes to
      our understanding of what makes Prx good enzymes or redox sensors. 

PMID- 25952725
TI  - NIR light controlled release of caged hydrogen sulfide based on upconversion
      nanoparticles.
AB  - A NIR light induced H2S release platform based on UCNPs was constructed. Under
      NIR light excitation, UCNPs can emit UV light which triggers H2S release in a
      spatial and temporal pattern. The platform was also employed to real-time monitor
      the delivery process in vivo, which may provide a new way for the use of H2S
      based therapeutics for a variety of diseases. 

PMID- 25952726
TI  - Treatment of acral persistent papular mucinosis using an Erbium-YAG laser.
AB  - BACKGROUND AND OBJECTIVES: Acral persistent papular mucinosis (APPM) is a rare
      condition with persistent flesh colored papules on the hands and extensor wrists.
      The authors aim to present a novel treatment option for this condition. PATIENTS
      AND METHODS: A female with APPM was treated using a 2940 nm Erbium-YAG laser with
      a 1 mm spotsize defocused to 2-3 mm with settings of 200-300 mJ until the lesion
      was flush with the surrounding skin. RESULTS: Healing of the wounds with
      resolution of the individually treated papules. CONCLUSIONS: Erbium-YAG lasers
      should be considered a treatment option for APPM.

PMID- 25952727
TI  - Interdisciplinary education and practice: Where are we with all that?

PMID- 25952728
TI  - Pharmacological assessment of the onset of action of aclidinium and
      glycopyrronium versus tiotropium in COPD patients and human isolated bronchi.
AB  - Preclinical studies suggested that aclidinium and glycopyrronium might have a
      faster onset of action than tiotropium. In this study we assessed the onset of
      action of aclidinium and glycopyrronium versus tiotropium, all administered at
      the approved clinical doses, in patients with moderate-to-severe chronic
      obstructive pulmonary disease (COPD) and in human isolated bronchi by using
      different concentrations. Sixteen COPD patients inhaled single doses of
      aclidinium 400ug, glycopyrronium 50MUg and tiotropium 18ug and FEV1 was measured
      to assess their onset of action. In human isolated bronchi the time to evoke half
      maximal relaxation of transmural stimulation was tested from 10nM to 1uM for each
      drug. Nine, eight and twelve patients did not achieve 15% increase of FEV1 after
      inhalation of aclidinium, glycopyrronium and tiotropium, respectively. Aclidinium
      (15.6+/-7.5min) and glycopyrronium (17.9+/-10.4min) enhanced 15% FEV1 more
      rapidly than tiotropium (42.5+/-19.4min), with no significant difference
      (P>0.05). In isolated airways, glycopyrronium elicited a dose-dependent onset of
      action (10nM: 8.2+/-1.3min, 100nM: 7.1+/-2.1min, 1MUM: 3.4+/-0.4min) that was
      faster compared to that induced by aclidinium (1MUM: 6.4+/-0.5min) and tiotropium
      (1MUM: 8.4+/-1.1min) (P<0.05), that halved the contractile tone only at the
      highest concentration. Bronchodilation induced by aclidinium and glycopyrronium
      was faster than that induced by tiotropium, but since our analysis was restricted
      to the acute effect of these LAMAs and the inhaled doses were not isoeffective,
      the real differences in their impact on the onset of bronchodilation will be
      definitely determined after a long-term challenge of these treatments at
      isoeffective doses in COPD patients. 

PMID- 25952729
TI  - Relaxation effect of a novel Danshensu/tetramethylpyrazine derivative on rat
      mesenteric arteries.
AB  - Danshen (Radix Salviae miltiorrhizae) and ChuanXiong (Ligusticum wallichii) are
      two traditional herbal medicines commonly used in China for the treatment of
      cardiovascular diseases. The active components in Danshen and ChuanXiong are
      Danshensu (DSS, (R)-3, 4-dihydroxyphenyllactic acid) and tetramethylpyrazine
      (TMP), respectively. In the present study, a new compound named ADTM, which is a
      conjugation of DSS and TMP, was synthesized and its effect on the contractility
      of rat mesenteric arteries was examined. The relaxation effect of ADTM on rat
      mesenteric arteries was studied using myography. The effects of ADTM on Ca(2+)
      channels were measured by Ca(2+) imaging and patch-clamp techniques. The results
      showed that ADTM caused a concentration-dependent relaxation of rat mesenteric
      arteries. This relaxation effect was not affected by the removal of endothelium
      or inhibitors of nitric oxide synthase, cyclooxygenase, guanylyl cyclase and
      adenylyl cyclase. Potassium channel blockers including tetraethylammonium,
      iberiotoxin, apamin, 4-aminopyridine, BaCl2 and glibenclamide also failed to
      inhibit the relaxation response to ADTM. ADTM inhibited CaCl2-induced
      contractions and reduced the Ca(2+) influx in isolated mesenteric arterial muscle
      cells. Our results suggest that ADTM may be a novel relaxing agent. Its mechanism
      of action involves the direct blockade of voltage-gated Ca(2+) channels in
      vascular smooth muscle cells, resulting in a decrease in Ca(2+) influx into the
      cells. 

PMID- 25952730
TI  - A real time genotyping PCR assay for polyomavirus BK.
AB  - BACKGROUND: Polyomavirus BK (BKV) may cause nephropathy in renal transplant
      recipients and hemorrhagic cystitis in bone marrow recipients. We developed real
      time PCRs (RT-PCR) to determine easily and rapidly the different BKV genotypes
      (BKGT) (I-IV). METHODS: On the VP1 gene a duplex of RT-PCRs was developed and
      validated to differentiate the four main BKGT. 212 BKV positive samples (21
      plasma, 191 urine) were tested with these specific PCRs. Of these 212 samples, 55
      PCR results were additionally confirmed by sequencing a VP1 gene fragment
      (nucleotide 1630-1956). RESULTS: For every genotype, a highly specific, precise
      and internally controlled assay was developed with a limit of detection of log 3
      copies per ml. In 18 (8.5%) of these samples genotyping was not successful due to
      a low viral load. By sequence analysis, the genotype of 46 out of 55 and 2 out of
      4 samples with double infection could be confirmed. CONCLUSIONS: This study
      describes RT-PCRs for detection of the main BKGT. It proved to be rapid, cheap
      and sensitive compared to sequencing. Double infections can also be detected.
      This method will be of value to investigate the role of BKV infection in relation
      to the genotype.

PMID- 25952731
TI  - Development of a blocking latex agglutination test for the detection of
      antibodies to chicken anemia virus.
AB  - A blocking latex agglutination test (b-LAT) developed in this study was evaluated
      for the detection of antibodies against chicken anemia virus (CAV) in chickens.
      Polystyrene latex beads were coupled with a neutralizing monoclonal antibody
      (mAb) to CAV (mAb-beads). When mAb-beads were mixed with antigens prepared from
      the lysate of MDCC-MSB1 cells infected with CAV, agglutination occurred. A short
      pre-incubation of CAV antigens with CAV-specific antiserum inhibited the
      agglutination of mAb-beads. The test results were obtained within 5min. The
      specificity of b-LAT was evaluated using sera from specific pathogen-free
      chickens and sera containing antibodies to avian influenza virus, Newcastle
      disease virus, infectious bursal disease virus, and Marek's disease virus;
      nonspecific agglutination and cross-reactivity with antibodies to unrelated
      viruses were not observed. The examination of 94 serum samples collected from
      commercial breeder chickens of various ages (17-63 weeks) revealed good agreement
      (93.6%, Kappa value=0.82) between b-LAT and a virus neutralization test, known to
      be most sensitive and specific in the detection of antibodies to CAV. These
      results indicate that b-LAT, a simple and rapid test, is a useful and reliable
      tool in CAV serology. 

PMID- 25952732
TI  - Recipient expression of ligands for donor inhibitory KIRs enhances NK-cell
      function to control leukemic relapse after haploidentical transplantation.
AB  - Natural killer (NK) cells that express self-HLA-specific receptors (where HLA is
      human leukocyte antigen) are "licensed" and more readily activated than
      unlicensed cells; therefore, NK-cell licensing could influence the antileukemia
      effects of NK cells following haploidentical stem cell transplantation (haplo
      SCT). In this study, we compared the functionality of reconstituting NK cells,
      based on CD107alpha expression and interferon-gammasecretion, in a cohort of 29
      patients that expressed (n = 8) or lacked (n = 21) class I human leukocyte
      antigens for donor inhibitory killer cell immunoglobulin-like receptors (KIRs)
      following T-cell-replete haplo-SCT. We also addressed whether recipient
      expression of class I ligands for donor inhibitory KIRs could predict relapse
      occurrence in another cohort of 188 patients. A longitudinal analysis indicated
      that patients presenting class I for all donor inhibitory KIRs showed more
      capable functional NK effector cells when tested against class I negative K562
      cells and primary leukemic cells within 3 months of transplantation. The lowest 7
      year relapse incidence was observed when donor KIRs were ligated by recipient
      class I (n = 60) compared with donor-host partnerships where donor KIR(+) cells
      were ligated by donor, but not recipient class I (n = 86, p = 0.026) or KIRs that
      were ligated by neither donor nor recipient class I (n = 42, p = 0.043). This
      study suggests that haplo-SCT recipients presenting class I for donor inhibitory
      KIRs promote NK-cell licensing, leading to decreased relapse rates. 

PMID- 25952733
TI  - Diagnostic Performance of 18F-FDG PET and PET/CT for the Detection of Recurrent
      Esophageal Cancer After Treatment with Curative Intent: A Systematic Review and
      Meta-Analysis.
AB  - The aim of this study was to assess the diagnostic performance of (18)F-FDG PET
      and integrated (18)F-FDG PET/CT for diagnosing recurrent esophageal cancer after
      initial treatment with curative intent. METHODS: The PubMed, Embase, and Cochrane
      library were systematically searched for all relevant literature using the key
      words "(18)F-FDG PET" and "esophageal cancer" and synonyms. Studies examining the
      diagnostic value of (18)F-FDG PET or integrated (18)F-FDG PET/CT, either in
      routine clinical follow-up or in symptomatic patients in whom recurrence of
      esophageal cancer was suspected, were deemed eligible for inclusion. The primary
      outcome was the presence of recurrent esophageal cancer as determined by
      histopathologic biopsy or clinical follow-up. Risk of bias and applicability
      concerns were assessed using the Quality Assessment of Diagnostic Accuracy
      Studies (QUADAS-2) tool. Sensitivities and specificities of individual studies
      were meta-analyzed using bivariate random-effects models. RESULTS: Eight eligible
      studies were included for meta-analysis, comprising 486 patients with esophageal
      cancer who underwent (18)F-FDG PET or PET/CT after previous treatment with
      curative intent. The quality of the included studies assessed by the QUADAS-2
      tool was considered reasonable; there were few concerns with regard to the risk
      of bias and applicability. Integrated (18)F-FDG PET/CT and standalone (18)F-FDG
      PET were used in 4 and 3 studies, respectively. One other study analyzed both
      modalities separately. In 4 studies, (18)F-FDG PET or PET/CT was performed as
      part of routine follow-up, whereas in 4 other studies the diagnostic test was
      performed on indication during clinical follow-up. Pooled estimates of
      sensitivity and specificity for (18)F-FDG PET and PET/CT in diagnosing recurrent
      esophageal cancer were 96% (95% confidence interval, 93%-97%) and 78% (95%
      confidence interval, 66%-86%), respectively. Subgroup analysis revealed no
      statistically significant difference in diagnostic accuracy according to type of
      PET scanner (standalone PET vs. integrated PET/CT) or indication of scanning
      (routine follow-up vs. on indication). CONCLUSION: (18)F-FDG PET and PET/CT are
      reliable imaging modalities with a high sensitivity and moderate specificity for
      detecting recurrent esophageal cancer after treatment with curative intent. The
      use of (18)F-FDG PET or PET/CT particularly allows for a minimal false-negative
      rate. However, histopathologic confirmation of (18)F-FDG PET- or PET/CT-suspected
      lesions remains required, because a considerable false-positive rate is noticed.

PMID- 25952734
TI  - Immuno-PET of Murine T Cell Reconstitution Postadoptive Stem Cell Transplantation
      Using Anti-CD4 and Anti-CD8 Cys-Diabodies.
AB  - The proliferation and trafficking of T lymphocytes in immune responses are
      crucial events in determining inflammatory responses. To study whole-body T
      lymphocyte dynamics noninvasively in vivo, we generated anti-CD4 and -CD8 cys
      diabodies (cDbs) derived from the parental antibody hybridomas GK1.5 and 2.43,
      respectively, for (89)Zr-immuno-PET detection of helper and cytotoxic T cell
      populations. METHODS: Anti-CD4 and -CD8 cDbs were engineered, produced via
      mammalian expression, purified using immobilized metal affinity chromatography,
      and characterized for T cell binding. The cDbs were site-specifically conjugated
      to maleimide-desferrioxamine for (89)Zr radiolabeling and subsequent small-animal
      PET/CT acquisition and ex vivo biodistribution in both wild-type mice and a model
      of hematopoietic stem cell (HSC) transplantation. RESULTS: Immuno-PET and
      biodistribution studies demonstrate targeting and visualization of CD4 and CD8 T
      cell populations in vivo in the spleen and lymph nodes of wild-type mice, with
      specificity confirmed through in vivo blocking and depletion studies.
      Subsequently, a murine model of HSC transplantation demonstrated successful in
      vivo detection of T cell repopulation at 2, 4, and 8 wk after HSC transplantation
      using the (89)Zr-radiolabeled anti-CD4 and -CD8 cDbs. CONCLUSION: These newly
      developed anti-CD4 and -CD8 immuno-PET reagents represent a powerful resource to
      monitor T cell expansion, localization, and novel engraftment protocols. Future
      potential applications of T cell-targeted immuno-PET include monitoring immune
      cell subsets in response to immunotherapy, autoimmunity, and lymphoproliferative
      disorders, contributing overall to preclinical immune cell monitoring.

PMID- 25952735
TI  - Dorsal-to-Ventral Shift in Midbrain Dopaminergic Projections and Increased
      Thalamic/Raphe Serotonergic Function in Early Parkinson Disease.
AB  - Loss of nigrostriatal neurons leading to dopamine depletion in the dorsal
      striatum is the pathologic hallmark of Parkinson disease contributing to the
      primary motor symptoms of the disease. However, Parkinson pathology is more
      widespread in the brain, affecting also other dopaminergic pathways and
      neurotransmitter systems, but these changes are less well characterized. This
      study aimed to investigate the mesencephalic striatal and extrastriatal
      dopaminergic projections together with extrastriatal serotonin transporter
      binding in Parkinson disease. METHODS: Two hundred sixteen patients with
      Parkinson disease and 204 control patients (patients without neurodegenerative
      parkinsonism syndromes and normal SPECT imaging) were investigated with SPECT
      using the dopamine/serotonin transporter ligand (123)I-N-omega-fluoropropyl-2beta
      carbomethoxy-3beta-(4-iodophenyl)nortropane ((123)I-FP-CIT) in the clinical
      setting. The group differences and midbrain correlations were analyzed voxel by
      voxel over the entire brain. RESULTS: We found that Parkinson patients had lower
      (123)I-FP-CIT uptake in the striatum and ventral midbrain but higher uptake in
      the thalamus and raphe nuclei than control patients. In patients with Parkinson
      disease, the correlation of the midbrain tracer uptake was shifted from the
      putamen to widespread corticolimbic areas. All findings were highly significant
      at the voxel level familywise error-corrected P value of less than 0.05.
      CONCLUSION: Our findings show that Parkinson disease is associated not only with
      the degeneration of the nigrostriatal dopamine neurotransmission, but also with a
      parallel shift toward mesolimbic and mesocortical function. Furthermore,
      Parkinson disease patients seem to have upregulation of brain serotonin
      transporter function at the early phase of the disease.

PMID- 25952736
TI  - 64Cu-DOTATATE PET for Neuroendocrine Tumors: A Prospective Head-to-Head
      Comparison with 111In-DTPA-Octreotide in 112 Patients.
AB  - Neuroendocrine tumors (NETs) can be visualized using radiolabeled somatostatin
      analogs. We have previously shown the clinical potential of (64)Cu-DOTATATE in a
      small first-in-human feasibility study. The aim of the present study was, in a
      larger prospective design, to compare on a head-to-head basis the performance of
      (64)Cu-DOTATATE and (111)In-diethylenetriaminepentaacetic acid (DTPA)-octreotide
      ((111)In-DTPA-OC) as a basis for implementing (64)Cu-DOTATATE as a routine.
      METHODS: We prospectively enrolled 112 patients with pathologically confirmed
      NETs of gastroenteropancreatic or pulmonary origin. All patients underwent both
      PET/CT with (64)Cu-DOTATATE and SPECT/CT with (111)In-DTPA-OC within 60 d. PET
      scans were acquired 1 h after injection of 202 MBq (range, 183-232 MBq) of (64)Cu
      DOTATATE after a diagnostic contrast-enhanced CT scan. Patients were followed for
      42-60 mo for evaluation of discrepant imaging findings. The McNemar test was used
      to compare the diagnostic performance. RESULTS: Eighty-seven patients were
      congruently PET- and SPECT-positive. No SPECT-positive cases were PET-negative,
      whereas 10 false-negative SPECT cases were identified using PET. The diagnostic
      sensitivity and accuracy of (64)Cu-DOTATATE (97% for both) were significantly
      better than those of (111)In-DTPA-OC (87% and 88%, respectively, P = 0.017). In
      84 patients (75%), (64)Cu-DOTATATE identified more lesions than (111)In-DTPA-OC
      and always at least as many. In total, twice as many lesions were detected with
      (64)Cu-DOTATATE than with (111)In-DTPA-OC. Moreover, in 40 of 112 cases (36%)
      lesions were detected by (64)Cu-DOTATATE in organs not identified as disease
      involved by (111)In-DTPA-OC. CONCLUSION: With these results, we demonstrate that
      (64)Cu-DOTATATE is far superior to (111)In-DTPA-OC in diagnostic performance in
      NET patients. Therefore, we do not hesitate to recommend implementation of (64)Cu
      DOTATATE as a replacement for (111)In-DTPA-OC.

PMID- 25952737
TI  - 18F-NaF Uptake by Atherosclerotic Plaque on PET/CT Imaging: Inverse Correlation
      Between Calcification Density and Mineral Metabolic Activity.
AB  - Several studies have highlighted the role of vascular (18)F-NaF uptake as a
      marker of ongoing calcium deposition. However, accumulation of (18)F-NaF is often
      inconsistent with localization of arterial plaque. Calcification activity and
      thus (18)F-NaF uptake might prevail in the earlier plaque stages. To test this
      hypothesis, we evaluated (18)F-NaF uptake in plaque of 3 different densities,
      using density as a marker of calcification progression. We also tested whether
      attenuation-weighted image reconstruction affects (18)F-NaF uptake in the
      different plaque stages. METHODS: Sixty-four oncologic patients (14 men and 50
      women; mean age, 65.3 +/- 8.2 y; range, 26-81 y) underwent (18)F-NaF PET/CT. A
      volume of interest was drawn on each plaque within the infrarenal aorta to assess
      mean standardized uptake value and attenuation (in Hounsfield units [HU]). Plaque
      was then categorized as light (<210 HU), medium (211-510 HU), or heavy (>510 HU).
      Standardized uptake value was normalized for blood (18)F-NaF activity to obtain
      the plaque target-to-background ratio (TBR). During this process, several focal,
      noncalcified areas of (18)F-NaF were identified (hot spots). The TBR of the hot
      spots was computed after isocontour thresholding. The TBR of a noncalcified
      control region was also calculated. In 35 patients, the TBR of non-attenuation
      corrected images was calculated. RESULTS: The average TBR was highest in light
      plaque (2.21 +/- 0.88), significantly lower in medium plaque (1.59 +/- 0.63, P <
      0.001), and lower still in heavy plaque (1.14 +/- 0.37, P < 0.0001 with respect
      to both light and medium plaque). The TBR of the control region was not
      significantly different from that of heavy plaque but was significantly lower
      than that of light and medium plaque (P < 0.01). Hot spots had the highest
      absolute TBR (3.89 +/- 1.87, P < 0.0001 vs. light plaque). TBRs originating from
      non-attenuation-corrected images did not significantly differ from those
      originating from attenuation-corrected images. CONCLUSION: Our results support
      the concept that (18)F-NaF is a feasible option in imaging molecular calcium
      deposition in the early stages of plaque formation, when active uptake mechanisms
      are the main determinants of calcium presence, but that retention of (18)F-NaF
      progressively decreases with increasing calcium deposition in the arterial wall.
      Our data suggest that non-attenuation-corrected reconstruction does not
      significantly affect evaluation of plaque of any thickness.

PMID- 25952738
TI  - 18F-FDG PET/CT and Colorectal Cancer: Value of Fourth and Subsequent Posttherapy
      Follow-up Scans for Patient Management.
AB  - The purpose of this study was to evaluate the added value of a fourth and
      subsequent follow-up PET/CT scans to clinical assessment and impact on patient
      management in patients with colorectal cancer. METHODS: This was an institutional
      review board-approved, retrospective study. Eight hundred twenty-two patients
      with biopsy-proven colorectal cancer, who underwent (18)F-FDG PET/CT, were
      identified from 2000 to 2012. Among these, 73 (8.9%) patients underwent 4 or more
      follow-up PET/CT scans, with a total of 313 fourth and subsequent follow-up
      PET/CT scans. Median follow-up from the fourth follow-up PET/CT scan was 41.7 mo.
      The added value of each follow-up PET/CT scan, for clinical assessment and the
      treatment changes subsequent to each follow-up PET/CT scan, was established.
      Overall survival prediction was established using Kaplan-Meier plots with a
      Mantel-Cox log-rank test. RESULTS: Of the 313 fourth and subsequent follow-up
      PET/CT scans, 174 (55.6%) were interpreted as positive and 139 (44.4%) were
      interpreted as negative for recurrence or metastases. Thirty-four (46.6%)
      patients died during the study period. PET/CT identified recurrence or metastasis
      in 40.0% of scans obtained without prior clinical suspicion and ruled out disease
      in 23.6% of scans obtained with prior clinical suspicion. The PET/CT scan
      resulted in treatment change after 34.2% (107/313) of the scans. New treatment
      was initiated after 24.0% (75/313) of the scans, and treatment was changed after
      8.0% (25/313) scans. There was a statistically significant difference in the
      overall survival between patients with a positive and all negative fourth and
      subsequent follow-up PET/CT scans at the patient level (log-rank, P = 0.001).
      CONCLUSION: The fourth and subsequent (18)F-FDG PET/CT scans obtained after
      primary treatment completion add value to clinical assessment and the management
      plan and provide prognostic information in patients with colorectal cancer.

PMID- 25952739
TI  - Quantitative Evaluation of Segmentation- and Atlas-Based Attenuation Correction
      for PET/MR on Pediatric Patients.
AB  - Pediatric imaging is regarded as a key application for combined PET/MR imaging
      systems. Because existing MR-based attenuation-correction methods were not
      designed specifically for pediatric patients, we assessed the impact of 2
      potentially influential factors: inter- and intrapatient variability of
      attenuation coefficients and anatomic variability. Furthermore, we evaluated the
      quantification accuracy of 3 methods for MR-based attenuation correction without
      (SEGbase) and with bone prediction using an adult and a pediatric atlas
      (SEGwBONEad and SEGwBONEpe, respectively) on PET data of pediatric patients.
      METHODS: The variability of attenuation coefficients between and within pediatric
      (5-17 y, n = 17) and adult (27-66 y, n = 16) patient collectives was assessed on
      volumes of interest (VOIs) in CT datasets for different tissue types. Anatomic
      variability was assessed on SEGwBONEad/pe attenuation maps by computing mean
      differences to CT-based attenuation maps for regions of bone tissue, lungs, and
      soft tissue. PET quantification was evaluated on VOIs with physiologic uptake and
      on 80% isocontour VOIs with elevated uptake in the thorax and abdomen/pelvis.
      Inter- and intrapatient variability of the bias was assessed for each VOI group
      and method. RESULTS: Statistically significant differences in mean VOI Hounsfield
      unit values and linear attenuation coefficients between adult and pediatric
      collectives were found in the lungs and femur. The prediction of attenuation maps
      using the pediatric atlas showed a reduced error in bone tissue and better
      delineation of bone structure. Evaluation of PET quantification accuracy showed
      statistically significant mean errors in mean standardized uptake values of -14%
      +/- 5% and -23% +/- 6% in bone marrow and femur-adjacent VOIs with physiologic
      uptake for SEGbase, which could be reduced to 0% +/- 4% and -1% +/- 5% using
      SEGwBONEpe attenuation maps. Bias in soft-tissue VOIs was less than 5% for all
      methods. Lung VOIs showed high SDs in the range of 15% for all methods. For VOIs
      with elevated uptake, mean and SD were less than 5% except in the thorax.
      CONCLUSION: The use of a dedicated atlas for the pediatric patient collective
      resulted in improved attenuation map prediction in osseous regions and reduced
      interpatient bias variation in femur-adjacent VOIs. For the lungs, in which
      intrapatient variation was higher for the pediatric collective, a patient- or
      group-specific attenuation coefficient might improve attenuation map accuracy.
      Mean errors of -14% and -23% in bone marrow and femur-adjacent VOIs can affect
      PET quantification in these regions when bone tissue is ignored.

PMID- 25952740
TI  - Practical PET Respiratory Motion Correction in Clinical PET/MR.
AB  - Respiratory motion during PET acquisition may lead to blurring in resulting
      images and underestimation of uptake parameters. The advent of integrated PET/MR
      scanners allows us to exploit the integration of modalities, using high spatial
      resolution and high-contrast MR images to monitor and correct PET images degraded
      by motion. We proposed a practical, anatomy-independent MR-based correction
      strategy for PET data affected by respiratory motion and showed that it can
      improve image quality both for PET acquired simultaneously to the motion
      capturing MR and for PET acquired up to 1 h earlier during a clinical scan.
      METHODS: To estimate the respiratory motion, our method needs only an extra 1-min
      dynamic MR scan, acquired at the end of the clinical PET/MR protocol. A
      respiratory signal was extracted directly from the PET list-mode data. This
      signal was used to gate the PET data and to construct a motion model built from
      the dynamic MR data. The estimated motion was then incorporated into the PET
      image reconstruction to obtain a single motion-corrected PET image. We evaluated
      our method in 2 steps. The PET-derived respiratory signal was compared with an MR
      measure of diaphragmatic displacement via a pencil-beam navigator. The motion
      corrected images were compared with uncorrected images with visual inspection,
      line profiles, and standardized uptake value (SUV) in focally avid lesions.
      RESULTS: We showed a strong correlation between the PET-derived and MR-derived
      respiratory signals for 9 patients, with a mean correlation of 0.89. We then
      showed 4 clinical case study examples ((18)F-FDG and (68)Ga-DOTATATE) using the
      motion-correction technique, demonstrating improvements in image sharpness and
      reduction of respiratory artifacts in scans containing pancreatic, liver, and
      lung lesions as well as cardiac scans. The mean increase in peak SUV (SUV(peak))
      and maximum SUV (SUV(max)) in a patient with 4 pancreatic lesions was 23.1% and
      34.5% in PET acquired simultaneously with motion-capturing MR, and 17.6% and
      24.7% in PET acquired 50 min before as part of the clinical scan. CONCLUSION: We
      showed that a respiratory signal can be obtained from raw PET data and that the
      clinical PET image quality can be improved using only a short additional PET/MR
      acquisition. Our method does not need external respiratory hardware or
      modification of the normal clinical MR sequences.

PMID- 25952741
TI  - 90Y Hepatic Radioembolization: An Update on Current Practice and Recent
      Developments.
AB  - Radioembolization is an established treatment modality that has been subjected to
      many improvements over the last decade. Developments are occurring at a high
      pace, affecting patient selection and treatment. The aim of this review is
      therefore to provide an overview of current practice, with a focus on recent
      developments in the field of radioembolization. Several practical issues and
      recommendations in the application of radioembolization will be discussed,
      ranging from patient selection to treatment response and future applications. 

PMID- 25952742
TI  - Isolation and Cr(VI) reduction characteristics of quinone respiration in
      Mangrovibacter plantisponsor strain CR1.
AB  - A Cr(VI)-reducing Mangrovibacter plantisponsor strain, CR1, was isolated from
      tannery effluent sludge and had quinone respiration characteristics. Its chromate
      (CrO4 (2-) ) resistance, quinone respiration characteristics, and Cr(VI)
      reduction efficiencies were evaluated in detail. Strain CR1 exhibited a high
      Cr(VI) resistance with a minimal inhibitory concentration (MIC) of 32 mM in LB
      medium, and its quinone respiration could occur when an electron donor and strain
      CR1 both existed in the reaction system. Cr(VI) reduction by strain CR1 was
      significantly enhanced by a factor of 0.4-4.3 with five different quinone
      compounds: anthraquinone-2,7-disulfonate, anthraquinone-1-sulfonate,
      anthraquinone-2-sulfonate (AQS), anthraquinone-2,6-disulfonate, and anthraquinone
      1,5-disulfonate. AQS was the best electron shuttle among them, and the greatest
      enhancement to the Cr(VI) bio-reduction was achieved with 0.96 mM AQS. The
      correlation between the reaction constant k (mg Cr(VI) g(-1) dry cell weight H(
      1) ) and thermodynamic temperature T (K) was expressed as an Arrhenius equation
      lnk=-7662.9/T+27.931(R2=0.9486); the activation energy Ea was 63.71 kJ mol(-1) ,
      and the pre-exponential factor A was 1.35 * 10(12)  mg Cr(VI) g(-1) dry cell
      weight H(-1) . During the Cr(VI) reduction process, the pH tended to become
      neutral, and the oxidation-reduction potential decreased to -440 mV. The
      efficient reduction of Cr(VI) mediated by a quinone respiration strain shows
      potential for the rapid anaerobic removal of Cr(VI). 

PMID- 25952743
TI  - Presenting Numeric Information with Percentages and Descriptive Risk Labels: A
      Randomized Trial.
AB  - BACKGROUND: Previous research demonstrated that providing (v. not providing)
      numeric information about the adverse effects (AEs) of medications increased
      comprehension and willingness to use medication but left open the question about
      which numeric format is best. The objective was to determine which of 4 tested
      formats (percentage, frequency, percentage + risk label, frequency + risk label)
      maximizes comprehension and willingness to use medication across age and numeracy
      levels. METHODS: In a cross-sectional internet survey (N = 368; American Life
      Panel, 15 May 2008 to 18 June 2008), respondents were presented with a
      hypothetical prescription medication for high cholesterol. AE likelihoods were
      described using 1 of 4 tested formats. Main outcome measures were risk
      comprehension (ability to identify AE likelihood from a table) and willingness to
      use the medication (7-point scale; not likely = 0, very likely = 6). RESULTS: The
      percentage + risk label format resulted in the highest comprehension and
      willingness to use the medication compared with the other 3 formats (mean
      comprehension in percentage + risk label format = 95% v. mean across the other 3
      formats = 81%; mean willingness = 3.3 v. 2.95, respectively). Comprehension
      differences between percentage and frequency formats were smaller among the less
      numerate. Willingness to use medication depended less on age and numeracy when
      labels were used. Generalizability is limited by the use of a sample that was
      older, more educated, and better off financially than national averages.
      CONCLUSIONS: Providing numeric AE-likelihood information in a percentage format
      with risk labels is likely to increase risk comprehension and willingness to use
      a medication compared with other numeric formats.

PMID- 25952744
TI  - Economic Evaluation of Pediatric Telemedicine Consultations to Rural Emergency
      Departments.
AB  - BACKGROUND: Comprehensive economic evaluations have not been conducted on
      telemedicine consultations to children in rural emergency departments (EDs).
      OBJECTIVE: We conducted an economic evaluation to estimate the cost,
      effectiveness, and return on investment (ROI) of telemedicine consultations
      provided to health care providers of acutely ill and injured children in rural
      EDs compared with telephone consultations from a health care payer prospective.
      METHODS: We built a decision model with parameters from primary programmatic
      data, national data, and the literature. We performed a base-case cost
      effectiveness analysis (CEA), a probabilistic CEA with Monte Carlo simulation,
      and ROI estimation when CEA suggested cost-saving. The CEA was based on program
      effectiveness, derived from transfer decisions following telemedicine and
      telephone consultations. RESULTS: The average cost for a telemedicine
      consultation was $3641 per child/ED/year in 2013 US dollars. Telemedicine
      consultations resulted in 31% fewer patient transfers compared with telephone
      consultations and a cost reduction of $4662 per child/ED/year. Our probabilistic
      CEA demonstrated telemedicine consultations were less costly than telephone
      consultations in 57% of simulation iterations. The ROI was calculated to be 1.28
      ($4662/$3641) from the base-case analysis and estimated to be 1.96 from the
      probabilistic analysis, suggesting a $1.96 return for each dollar invested in
      telemedicine. Treating 10 acutely ill and injured children at each rural ED with
      telemedicine resulted in an annual cost-savings of $46,620 per ED. LIMITATIONS:
      Telephone and telemedicine consultations were not randomly assigned, potentially
      resulting in biased results. CONCLUSIONS: From a health care payer perspective,
      telemedicine consultations to health care providers of acutely ill and injured
      children presenting to rural EDs are cost-saving (base-case and more than half of
      Monte Carlo simulation iterations) or cost-effective compared with telephone
      consultations.

PMID- 25952746
TI  - Sll0751 and Sll1041 are involved in acid stress tolerance in Synechocystis sp.
      PCC 6803.
AB  - The ATP-binding cassette (ABC) transporter is a multi-subunit membrane protein
      complex involved in lipid transport and acid stress tolerance in the
      cyanobacterium Synechocystis sp. PCC 6803. This organism has two sets of three
      ABC transporter subunits: Slr1045 and Slr1344, Sll0751 and Sll1002, and Sll1001
      and Sll1041. We previously found that Slr1045 is essential for survival under
      acid stress condition (Tahara et al. 2012). In the present study, we examined the
      participation of other ABC transporter subunits in acid stress tolerance using a
      deletion mutant series of Synechocystis sp. PCC 6803. Although Slr1344 is highly
      homologous to Slr1045, Deltaslr1344 cells were not susceptible to acid stress.
      Deltasll0751 and Deltasll1041 cells displayed acid stress sensitivity, whereas
      Deltasll1001/sll1002 double mutant cells grew normally. Under high- and low
      temperature stress conditions, the growth rate of Deltaslr1344 and
      Deltasll1001/sll1002 cells did not differ from WT cells, whereas Deltasll0751 and
      Deltasll1041 cells showed significant growth retardation, as previously observed
      in Deltaslr1045 cells. Moreover, nile red staining showed more lipid accumulation
      in Deltaslr1045, Deltasll0751, and Deltasll1041 cells than in WT cells. These
      results suggest that Slr1045, Sll0751, and Sll1041 function together as a lipid
      transport complex in Synechocystis sp. PCC 6803 and are essential for growth
      under various stresses. 

PMID- 25952745
TI  - Relevance of nutrient media composition for hydrogen production in Chlamydomonas.
AB  - Microalgae are capable of biological H2 photoproduction from water, solar energy,
      and a variety of organic substrates. Acclimation responses to different nutrient
      regimes finely control photosynthetic activity and can influence H2 production.
      Hence, nutrient stresses are an interesting scenario to study H2 production in
      photosynthetic organisms. In this review, we mainly focus on the H2-production
      mechanisms in Chlamydomonas reinhardtii and the physiological relevance of the
      nutrient media composition when producing H2.

PMID- 25952747
TI  - Relationship between daily physical activity and aerobic fitness in adults with
      cystic fibrosis.
AB  - BACKGROUND: The best clinical practice to investigate aerobic fitness includes
      measurements obtained during cardiopulmonary exercise testing (CPET), however it
      remains an underutilised clinical measure in cystic fibrosis (CF). To investigate
      this further, different methods of quantifying exercise capacity in CF are
      required. The possibility that measuring physical activity (PA) by a portable
      accelerometer could be used to assess the CF aerobic state and could be added
      among the CPET surrogates has not been investigated. The aim of this study was to
      examine the relationship between PA and exercise fitness both at submaximal and
      maximal levels in clinically stable adults with CF. METHODS: Thirty CF patients
      (FEV1 71 +/- 19% predicted) and fifteen healthy controls undertook an incremental
      CPET on a cycle ergometer. CPET-related measurements included: oxygen uptake
      (V'O2), carbon dioxide production (V'CO2), ventilatory profile, heart rate (HR)
      and oxygen pulse (V'O2/HR) throughout exercise and at lactic threshold (LT) and
      peak. LT measures represent submaximal exercise related data. PA was assessed
      using the accelerometer SenseWear Pro3 Armband. RESULTS: Moderate (>4.8 metabolic
      equivalents (METS)) and moderate + vigorous (>7.2 METS) PA was related to V'O2 (p
      = 0.005 and p = 0.009, respectively) and work rate (p = 0.004 and p = 0.002,
      respectively) at LT. Moderate PA or greater was positively related to peak V'O2
      (p = 0.005 and p = 0.003, respectively). Daily PA levels were similar in CF and
      healthy controls. Except for peak values, V'O2 profile and the V'O2 at LT were
      comparable between CF and healthy controls. CONCLUSIONS: In adult CF patients
      daily PA positively correlated with aerobic capacity. PA measurements are a
      valuable tool in the assessment of exercise performance in an adult CF population
      and could be used for interventional exercise trials to optimize exercise
      performance and health status. PA levels and parameters obtained at submaximal
      exercise are similar in CF and in healthy controls.

PMID- 25952748
TI  - Mechanical Thrombectomy of M2-Occlusion.
AB  - BACKGROUND: There is growing evidence for the efficacy of mechanical thrombectomy
      in acute stroke patients with large-vessel occlusions in the anterior
      circulation. Although distal occlusions of the middle cerebral artery (MCA) can
      cause severe clinical symptoms, endovascular therapy is not considered here as
      the first choice. The aim of our study was to prove the efficacy and safety of
      mechanical thrombectomy for distal occlusion types in the anterior circulation
      (M2-segment). METHODS: Stentretriever-based thrombectomy was performed in 119
      patients with acute MCA occlusions between October 2011 and April 2013: 104
      (87.4%) were M1- and 15 (12.6%) M2-occlusions. These groups were compared with
      regard to recanalization success, periprocedural complications, hemorrhage, and
      modified Rankin Scale (mRS) at 90 days. RESULTS: Thrombolysis in cerebral
      infarction 2b/3 reperfusion was more frequent in M2- than in M1-occlusions (93.3%
      versus 76.0%; P = .186). There was no significant difference in the mean National
      Institutes of Health Stroke Scale between the M1- and the M2-group both at
      admission and at discharge (16.18 +/- 7.30 versus 13.73 +/- 8.30, P = .235; 9.36
      +/- 8.60 versus 7.43 +/- 9.84, P = .446). A good clinical outcome (mRS 0-2) at 3
      months was more frequent in the M2-group (60% versus 43.3%; P = .273) and
      mortality was higher in the M1-group (21.2% versus 6.7%; P = .297). There were 3
      periprocedural complications in the M1- and none in the M2-group. CONCLUSIONS:
      Endovascular treatment of M2-occlusions in severely affected patients is not
      associated with a higher procedural risk or postprocedural hemorrhage. Compared
      with M1-occlusions, there was a greater chance for a good angiographic and
      clinical result in our case series. Therefore, stentretriever-based thrombectomy
      should also be considered for patients with severe symptoms because of an acute
      M2-occlusion.

PMID- 25952749
TI  - Mono- and bimetallic zwitterionic chromium(0) and tungsten(0) allenyls.
AB  - A series of stable chiral (racemic), formally neutral, zwitterionic mono- and
      bimetallic M(CO)5[C(OEt)?C?CR(NHC)] (M = Cr, W) sigma-allenyls are ready
      available by the addition of N-heterocyclic carbenes (NHCs) to Cr(0) and W(0)
      alkynyl Fischer carbene complexes. Different classes of NHCs, (e.g., 1,3
      bis(2,4,6-trimethylphenyl)imidazol-2-ylidene, 1,3-bis(2,4,6
      trimethylphenyl)imidazolin-2-ylidene, and their six- and seven-membered analogues
      and 1,3-bis(dimethyl)imidazol-2-ylidene) were employed as nucleophiles in these C
      C bond-forming reactions yielding the novel complexes in essentially quantitative
      yields. A systematic experimental and computational study of the electronic
      properties of the Cr- and W-allenyls shows that their UV-vis spectra are directly
      influenced by the structure of the heterocyclic moiety derived from the NHC (ring
      size, substituents on the N atoms) and by the nature of the metal fragment
      (Cr/W). The electron-releasing nature of these complexes allows them to
      participate in electron-transfer reactions in the ground state, leading to a type
      of charged alpha,beta-unsaturated Fischer carbenes that incorporate an NHC
      fragment in their structure. 

PMID- 25952751
TI  - Evaluation of total oxidant and antioxidant status in dogs under different CO2
      pneumoperitoneum conditions.
AB  - BACKGROUND: The induction of the pneumoperitoneum increases intraabdominal
      pressure (IAP), causing splanchnic ischemia, whereas its deflation normalizes IAP
      and splanchnic blood flow. We investigated the oxidant-antioxidant status of dogs
      who underwent low pressure (7 mm Hg), standard pressure (12 mm Hg), and high
      pressure (15 mm Hg) pneumoperitoneum. RESULTS: Twenty-four beagle dogs (12 males
      and 12 females), 4-6 years old, weighing 8-11 kg were used. The animals were
      assigned to one of four groups (n = 6 dogs). Group 1 served as a control; these
      animals received only anaesthesia for 90 min. In groups 2, 3 and 4, intra
      abdominal pressure was increased to 7, 12 and 15 mmHg, respectively, and
      maintained for 60 min. Total oxidant status (TOS) and total antioxidant status
      (TAS) were determined in venous blood samples. The percentage ratio of TOS to TAS
      provided an oxidative stress index (OSI). No significant difference in TOS levels
      was found among the groups. A significant decrease in TAS levels and an increase
      in OSI levels were observed at 90 min and 24 h of pneumoperitoneum deflation
      within group 4. No differences were found among the groups. CONCLUSIONS: A high
      pressure pneumoperitoneum induced significant changes in TAS and OSI. In
      addition, TOS and TAS levels are useful markers for evaluating changes in the
      oxidative status caused by a pneumoperitoneum during laparoscopy. Furthermore, a
      low-pressure pneumoperitoneum could attenuate oxidative stress induced by CO2
      insufflation in dogs.

PMID- 25952750
TI  - Mesothelioma patient derived tumor xenografts with defined BAP1 mutations that
      mimic the molecular characteristics of human malignant mesothelioma.
AB  - BACKGROUND: The development and evaluation of new therapeutic approaches for
      malignant mesothelioma has been sparse due, in part, to lack of suitable tumor
      models. METHODS: We established primary mesothelioma cultures from pleural and
      ascitic fluids of five patients with advanced mesothelioma. Electron microscopy
      and immunohistochemistry (IHC) confirmed their mesothelial origin. Patient
      derived xenografts were generated by injecting the cells in nude or SCID mice,
      and malignant potential of the cells was analyzed by soft agar colony assay.
      Molecular profiles of the primary patient tumors, early passage cell cultures,
      and patient derived xenografts were assessed using mutational analysis,
      fluorescence in situ hybridization (FISH) analysis and IHC. RESULTS: Primary
      cultures from all five tumors exhibited morphologic and IHC features consistent
      to those of mesothelioma cells. Mutations of BAP1 and CDKN2A were each detected
      in four tumors. BAP1 mutation was associated with the lack of expression of BAP1
      protein. Three cell cultures, all of which were derived from BAP1 mutant primary
      tumors, exhibited anchorage independent growth and also formed tumors in mice,
      suggesting that BAP1 loss may enhance tumor growth in vivo. Both early passage
      cell cultures and mouse xenograft tumors harbored BAP1 mutations and CDKN2A
      deletions identical to those found in the corresponding primary patient tumors.
      CONCLUSIONS: The mesothelioma patient derived tumor xenografts with mutational
      alterations that mimic those observed in patient tumors which we established can
      be used for preclinical development of novel drug regimens and for studying the
      functional aspects of BAP1 biology in mesothelioma.

PMID- 25952752
TI  - The changing landscape of care: does ethics education have a new role to play in
      health practice?
AB  - BACKGROUND: In the UK, higher education and health care providers share
      responsibility for educating the workforce. The challenges facing health practice
      also face health education and as educators we are implicated, by the way we
      design curricula and through students' experiences and their stories. This paper
      asks whether ethics education has a new role to play, in a context of major
      organisational change, a global and national austerity agenda and the
      ramifications of disturbing reports of failures in care. It asks: how would it be
      different if equal amounts of attention were given to the conditions in which
      health decisions are made, if the ethics of organisational and policy decisions
      were examined, and if guiding collaborations with patients and others who use
      services informed ethics education and its processes? DISCUSSION: This is in
      three parts. In part one an example from an inspection report is used to question
      the ways in which clinical events are decontextualised and constructed for
      different purposes. Ramifications of a decision are reflected upon and a case
      made for different kinds of allegiances to be developed. In part two I go on to
      broaden the scope of ethics education and make a case for beginning with the
      messy realities of practice rather than with overarching moral theories. The
      importance of power in ethical practice is introduced, and in part three the need
      for greater political and personal awareness is proposed as a condition of moral
      agency. SUMMARY: This paper proposes that ethics education has a new contribution
      to make, in supporting and promoting ethical practice - as it is defined in and
      by the everyday actions and decisions of practitioners and people who need health
      services. Ethics education that promotes moral agency, rather than problem
      solving approaches, would explore not only clinical problems, but also the
      difficult and contested arenas in which they occur. It would seek multiple
      perspectives and would begin with places and people, and their priorities. It
      would support students to locate their practice in imperfect global contexts, and
      to understand how individual and collective forms of power can influence
      healthcare quality.

PMID- 25952753
TI  - A modified multiplex ligation-dependent probe amplification method for the
      detection of 22q11.2 copy number variations in patients with congenital heart
      disease.
AB  - BACKGROUND: Copy number variations (CNVs) of chromosomal region 22q11.2 are
      associated with a subset of patients with congenital heart disease (CHD).
      Accurate and efficient detection of CNV is important for genetic analysis of CHD.
      The aim of the study was to introduce a novel approach named CNVplex(r), a high
      throughput analysis technique designed for efficient detection of chromosomal
      CNVs, and to explore the prevalence of sub-chromosomal imbalances in 22q11.2 loci
      in patients with CHD from a single institute. RESULTS: We developed a novel
      technique, CNVplex(r), for high-throughput detection of sub-chromosomal copy
      number aberrations. Modified from the multiplex ligation-dependent probe
      amplification (MLPA) method, it introduced a lengthening ligation system and four
      universal primer sets, which simplified the synthesis of probes and significantly
      improved the flexibility of the experiment. We used 110 samples, which were
      extensively characterized with chromosomal microarray analysis and MLPA, to
      validate the performance of the newly developed method. Furthermore, CNVplex(r)
      was used to screen for sub-chromosomal imbalances in 22q11.2 loci in 818 CHD
      patients consecutively enrolled from Shanghai Children's Medical Center. In the
      methodology development phase, CNVplex(r) detected all copy number aberrations
      that were previously identified with both chromosomal microarray analysis and
      MLPA, demonstrating 100% sensitivity and specificity. In the validation phase,
      22q11.2 deletion and 22q11.2 duplication were detected in 39 and 1 of 818
      patients with CHD by CNVplex(r), respectively. Our data demonstrated that the
      frequency of 22q11.2 deletion varied among sub-groups of CHD patients. Notably,
      22q11.2 deletion was more commonly observed in cases with conotruncal defect
      (CTD) than in cases with non-CTD (P<0.001). With higher resolution and more
      probes against selected chromosomal loci, CNVplex(r) also identified several
      individuals with small CNVs and alterations in other chromosomes. CONCLUSIONS:
      CNVplex(r) is sensitive and specific in its detection of CNVs, and it is an
      alternative to MLPA for batch screening of pathogenetic CNVs in known genomic
      loci.

PMID- 25952754
TI  - Coupled reversion and stream-hyporheic exchange processes increase environmental
      persistence of trenbolone metabolites.
AB  - Existing regulatory frameworks for aquatic pollutants in the United States are
      idealized, often lacking mechanisms to account for contaminants characterized by
      (1) bioactivity of both the parent and transformation products and (2) reversible
      transformations (that is, metastable products) driven by chemical or physical
      heterogeneities. Here, we modelled a newly discovered product-to-parent reversion
      pathway for trenbolone acetate (TBA) metabolites. We show increased exposure to
      the primary metabolite, 17alpha-trenbolone (17alpha-TBOH), and elevated
      concentrations of the still-bioactive primary photoproduct hydroxylated 17alpha
      TBOH, produced via phototransformation and then converted back to 17alpha
      trenbolone in perpetually dark hyporheic zones that exchange continuously with
      surface water photic zones. The increased persistence equates to a greater
      potential hazard from parent-product joint bioactivity at locations and times
      when reversion is a dominant trenbolone fate pathway. Our study highlights
      uncertainties and vulnerabilities with current paradigms in risk
      characterization. 

PMID- 25952755
TI  - A family of dinuclear lanthanide(III) complexes from the use of a tridentate
      Schiff base.
AB  - The use of N-salicylidene-o-aminophenol (H2saph) in 4f-metal chemistry has led to
      the isolation of seven new isostructural lanthanide(iii) [Ln(III)] complexes.
      More specifically the Ln(NO3)3.xH2O/H2saph/Et3N (1 : 1 : 1) reaction mixtures in
      DMF/MeCN gave complexes [Ln2(NO3)2(saph)2(DMF)4] (Ln = Sm (); Eu (); Gd (); Tb
      (); Dy (); Ho (); Er ()) in good yields (~65%). The structures of the isomorphous
      complexes and were solved by single-crystal X-ray crystallography; the other
      complexes are proposed to be isostructural with and based on elemental analyses,
      IR spectra and powder XRD patterns. The two Ln(III) atoms in the centrosymmetric
      molecules of and are doubly bridged by the deprotonated iminophenolato oxygen
      atoms of two nearly planar eta(1):eta(1):eta(2):MU saph(2-) ligands. The imino
      nitrogen and five terminal oxygen atoms (the salicylaldiminate, two from one
      bidentate chelating nitrato group and two from two DMF ligands) complete square
      antiprismatic coordination at each metal centre. The IR spectra of the complexes
      are discussed in terms of the coordination modes of the ligands present in the
      complexes. Solid-state emission studies for all display identical ligand-based
      photoluminescence. Dc magnetic susceptibility studies in the 2-300 K range reveal
      the presence of a weak, intramolecular antiferromagnetic exchange interaction (J
      = -0.19(1) cm(-1) based on the spin Hamiltonian H = -J(SGd.SGd')) for and
      probably ferromagnetic exchange interaction within the molecules of and . Ac
      magnetic susceptibility measurements in zero dc field show temperature- and
      frequency-dependent out-of-phase signals with two well defined, thermally
      activated processes for , suggesting potential single-molecule magnetism
      character. The Ueff value is 17.4 cm(-1) for the higher temperature process and
      16.2 cm(-1) for the lower temperature one. The combination of photoluminescence
      and single-molecule behaviour in the Dy complex is critically discussed. 

PMID- 25952757
TI  - Birt-Hogg-Dube syndrome and intracranial vascular pathologies.
AB  - Birt-Hogg-Dube syndrome, first described in 1977, is a rare autosomal dominant
      condition that commonly presents with skin lesions, including fibrofolliculomas
      and trichodiscomas; pulmonary cysts; spontaneous pneumothoraces; and renal
      cancer. We present the only known cases of intracranial vascular pathologies in
      patients with Birt-Hogg-Dube syndrome. We present three cases (three female; age
      range 18-50) of intracranial vascular lesions in Birt-Hogg-Dube patients,
      including two aneurysms and one arteriovenous malformation, and review one
      previously reported case of carotid aplasia. Due to the rarity of Birt-Hogg-Dube
      syndrome and significant variations in its clinical presentation, it is difficult
      to assess whether or not Birt-Hogg-Dube patients are predisposed to intracranial
      vascular pathologies. We hypothesize that increased transcription of hypoxia
      inducible factor 1-alpha, resulting from a mutated form of the protein folliculin
      transcribed by the Birt-Hogg-Dube gene, may be associated with vascular
      pathogenesis in Birt-Hogg-Dube patients and thus provide a possible molecular
      basis for a link between these two conditions. 

PMID- 25952756
TI  - Genotype-phenotype analysis of von Hippel-Lindau syndrome in fifteen Indian
      families.
AB  - The general prevalence of the familial multi-organ tumor disorder, von Hippel
      Lindau syndrome (VHL), was estimated to be 1 in 25-40,000 in western studies two
      decades back. Few studies were done in Indian sub-continent, amidst a surge in
      clinical reports on VHL specific manifestations. The syndrome is correlated with
      mutations of the gene VHL (located in Chr 3p25.3). We aimed to conduct a
      prospective case series describing phenotypic and genotypic characteristics in
      Indian population. The VHL-specific clinical and radiological features were
      collected from patients and family members. Genotypic changes such as
      deletion/duplication or point mutation in the VHL locus were identified using
      sequencing and MLPA. Thirty-one subjects, from fifteen families with diagnosed
      VHL, were included in the study. Multicystic pancreas was found in 71% (22/31),
      CNS hemangioblastoma in 68% (21/31), renal cell carcinoma and retinal angiomas in
      23% (7/31) each, pheochromocytoma in 9.7% (3/31) of the population and
      endolymphatic sac tumor in one subject. Four families (9 subjects) had full
      length deletion of VHL, three families (4 subjects) had a deletion of exon 3,
      eight families (18 subjects) had different exonic, splice-site and intronic point
      mutations and one subject had a de novo in-frame indel in exon 1. Multicystic
      pancreas and CNS hemangioblastomas were the most common manifestations in our
      population. The phenotypic expression patterns in terms of tumorigenesis, tissue
      tropism and penetrance in comparison to the genotypic features were found to be
      different from previous correlative studies.

PMID- 25952758
TI  - Periodontal status and oral health-related quality of life in elderly residents
      of aged care homes in Delhi.
AB  - AIM: The aim of the present study was to explore the associations between
      clinical periodontal findings and oral health-related quality of life in elderly
      people residing in the aged care homes of Delhi, India. METHODS: A cross
      sectional study was carried out among 500 residents of aged care homes across
      Delhi. Data were collected by carrying out clinical oral examinations and by
      filling a self-administered questionnaire. Oral health-related quality of life
      was assessed by a pretested Hindi version of the Geriatric Oral Health Assessment
      Index (GOHAI-Hi). Periodontal status was assessed using the Community Periodontal
      Index - CPI, and loss of attachment and tooth mobility was assessed using a
      modified Miller's index. RESULTS: Of a total of 500 participants, 221 (44.20%)
      were men and 279 (55.80%) were women The mean additive score GOHAI score was
      41.57 +/- 6.07 and the mean number of negative impacts or mean simple count GOHAI
      score was 6.27 +/- 1.54. Mean GOHAI scores were significantly higher among men
      than women, and were found to be decreasing continuously with the increasing age
      categories. Tooth mobility and loss of attachment scores were found to be
      significantly associated with oral health-related quality of life, whereas
      Community Periodontal Index scores showed a negative correlation with it.
      CONCLUSION: The geriatric population, especially those in aged care homes, is a
      special need group because of their inability to access dental care rather than
      some particular feature of their oral or general health The findings of the
      present study point to a need to improve access to oral healthcare for this
      elderly population.

PMID- 25952759
TI  - Relational Memory Processes in Adults with Autism Spectrum Disorder.
AB  - Research into memory in Autism Spectrum Disorder (ASD) suggests intact item
      memory but difficulties in forming relations between items (Bowler, Gaigg, &
      Lind, 2011). In this study, we tested memory for items as well as for sequential,
      spatial, and associative relations between items with the same paradigm using
      abstract shapes in ASD and typically developing (TD) individuals. Participants
      studied shape triplets on a computer screen and memory was subsequently tested
      either for the individual items making up the triplets, the screen-locations, the
      order or the combinations of items presented at study. Contrary to our
      predictions, performance was significantly lower in the ASD group on all four
      tasks. The result raises questions about how intact item memory is in ASD, which
      role task complexity plays, and how item-specific versus relational processing
      affect task performance. One possibility is that TD individuals relied more on
      relational processing in the current study and might have therefore had an
      advantage over ASD individuals. This idea is supported by the result of a
      preliminary analysis of age-related differences in memory across the midadult
      lifespan in both groups. Age seems to affect order memory less in ASD compared
      with TD individuals where it leads to a significant decrease in performance. This
      might indicate a decrease in relational processing in TD but not ASD individuals
      with increasing age. More research is needed to answer questions about the change
      in cognition in ASD individuals across the lifespan.

PMID- 25952761
TI  - Epidemiology of yoga-related injuries in Canada from 1991 to 2010: a case series
      study.
AB  - The aim is to describe the epidemiology of yoga injuries presenting to select
      Canadian emergency departments (EDs). Those who presented with a yoga injury to a
      Canadian ED participating in the Canadian Hospitals Injury Reporting and
      Prevention Program and had completed a data collection form between 1991 and 2010
      were included. Demographic and injury characteristics were tabulated and injury
      profiles of children were compared to adults. Sixty-six individuals (48 female,
      18 male) who sustained 67 injuries were included. The median age was 19
      (intraquartile range: 13, 32) and 73% of individuals were injured after 2005 (p =
      0.0003). Sprain was the most common injury (23/67, 34%) and the most common body
      region injured was the lower extremity (27/67, 42%). Significantly more children
      were injured while being instructed than adults (p = 0.003) but more adults
      required treatment (p = 0.023). Although yoga-related injuries presenting to an
      ED are not common, the number of injuries are increasing. 

PMID- 25952760
TI  - Dopamine receptor blockade improves pulmonary gas exchange but decreases exercise
      performance in healthy humans.
AB  - Pulmonary gas exchange, as evaluated by the alveolar-arterial oxygen difference
      (A-aDO2), is impaired during intense exercise, and has been correlated with
      recruitment of intrapulmonary arteriovenous anastomoses (IPAVA) as measured by
      agitated saline contrast echocardiography. Previous work has shown that dopamine
      (DA) recruits IPAVA and increases venous admixture (Qs/Qt) at rest. As
      circulating DA increases during exercise, we hypothesized that A-aDO2 and IPAVA
      recruitment would be decreased with DA receptor blockade. Twelve healthy males
      (age: 25 +/- 6 years, VO2 max : 58.6 +/- 6.5 ml kg(-1) min(-1) ) performed two
      incremental staged cycling exercise sessions after ingestion of either placebo or
      a DA receptor blocker (metoclopramide 20 mg). Arterial blood gas,
      cardiorespiratory and IPAVA recruitment (evaluated by agitated saline contrast
      echocardiography) data were obtained at rest and during exercise up to 85% of VO2
      max . On different days, participants also completed incremental exercise tests
      and exercise tolerance (time-to-exhaustion (TTE) at 85% of VO2 max ) with or
      without dopamine blockade. Compared to placebo, DA blockade did not change O2
      consumption, CO2 production, or respiratory exchange ratio at any intensity. At
      85% VO2 max , DA blockade decreased A-aDO2, increased arterial O2 saturation and
      minute ventilation, but did not reduce IPAVA recruitment, suggesting that
      positive saline contrast is unrelated to A-aDO2. Compared to placebo, DA blockade
      decreased maximal cardiac output, VO2 max and TTE. Despite improving pulmonary
      gas exchange, blocking dopamine receptors appears to be detrimental to exercise
      performance. These findings suggest that endogenous dopamine is important to the
      normal cardiopulmonary response to exercise and is necessary for optimal high
      intensity exercise performance.

PMID- 25952762
TI  - H(N), N, C(alpha), C(beta) and C' assignments of the intrinsically disordered C
      terminus of human adenosine A2A receptor.
AB  - The C-terminus of the human adenosine A2A receptor differs from the other human
      adenosine receptors by its exceptional length and lack of a canonical cysteine
      residue. We have previously structurally characterized this C-terminal domain and
      its interaction with calmodulin. It was shown to be structurally disordered and
      flexible, and to bind calmodulin with high affinity in a calcium-dependent
      manner. Interaction with calmodulin takes place at the N-terminal end of the A2A
      C-terminal domain without major conformational changes in the latter. NMR was one
      of the biophysical methods used in the study. Here we present the H(N), N,
      C(alpha), C(beta) and C' chemical shift assignments of the free form of the C
      terminus residues 293-412, used in the NMR spectroscopic characterization of the
      domain. 

PMID- 25952763
TI  - Efficacy of Trypsin in Treating Coral Snake Envenomation in the Porcine Model.
AB  - Antivenom is the definitive treatment for venomous snakebites. Alternative
      treatments warrant investigation because antivenom is sometimes unavailable,
      expensive, and can have deleterious side effects. This study assesses the
      efficacy of trypsin to treat coral snake envenomation in an in vivo porcine
      model. A randomized, blinded study was conducted. Subjects were 13 pigs injected
      subcutaneously with 1 mL of eastern coral snake venom (10 mg/mL) in the right
      distal hind limb. After 1 min, subjects were randomized to have the envenomation
      site injected with either 1 mL of saline or 1 mL of trypsin (100 mg/mL) by a
      blinded investigator. Clinical endpoint was survival for 72 h or respiratory
      depression defined as respiratory rate <15 breaths per minute, falling pulse
      oximetry, or agonal respirations. Fisher's exact t test was used for between
      group comparisons. Average time to toxicity for the saline control was 263 min
      (191-305 min). The development of respiratory depression occurred more frequently
      in control pigs than treated pigs (p = 0.009). Four of the six pigs that received
      trypsin survived to the end of the 3-day study. No control pigs survived. Two of
      the trypsin treatment pigs died with times to toxicity of 718 and 971 min.
      Survival to 12 and 24 h was significantly greater in the trypsin treatment group
      (p = 0.002, p = 0.009, respectively). Local injection of trypsin, a proteolytic
      enzyme, at the site of envenomation decreased the toxicity of eastern coral snake
      venom and increased survival significantly. Further investigation is required
      before these results can be extended to human snakebites.

PMID- 25952764
TI  - The Global Educational Toxicology Uniting Project (GETUP): an Analysis of the
      First Year of a Novel Toxicology Education Project.
AB  - The international boundaries to medical education are becoming less marked as new
      technologies such as multiuser videoconferencing are developed and become more
      accessible to help bridge the communication gaps. The Global Educational
      Toxicology Uniting Project (GETUP) is aimed at connecting clinicians in countries
      with established clinical toxicology services to clinicians in countries without
      clinical toxicologists around the globe. Centers that manage or consult on
      toxicology cases were registered through the American College of Medical
      Toxicology website via Survey Monkey(r). Data was analyzed retrospectively from
      February 2014 to January 2015. Google hangouts(r) was used as the main
      conferencing software, but some sites preferred the use of Skype(r). Registration
      data included contact details and toxicology background and qualifications.
      Thirty sites in 19 different countries in Australasia, Europe, Africa, and
      America were registered. Twenty-eight (93 %) sites were located in a major urban
      center, one (3.5 %) site in a major rural center and one (3.5 %) a private
      practice. Expectations of GETUP included sharing toxicology cases and education
      (30, 100 % of sites), assistance with toxicology management guidelines (2, 7 %),
      assistance with providing a toxicology teaching curriculum in languages other
      than English (2, 7 %), and managing toxicology presentations in resource-poor
      settings, international collaboration, and toxicovigilance (2 sites, 7 %). Twenty
      two conferences were performed during the first 12 months with a mean of 3 cases
      per conference. GETUP has connected countries and clinical units with and without
      toxicology services and will provide a platform to improve international
      collaboration in clinical toxicology.

PMID- 25952765
TI  - Computational prediction of phenotype in haemophilia A.

PMID- 25952766
TI  - High Incidence of Low Catheter-Tissue Contact Force at the Cavotricuspid Isthmus
      During Catheter Ablation of Atrial Flutter: Implications for Achieving Isthmus
      Block.
AB  - INTRODUCTION: Recurrent atrial flutter following cavotricuspid isthmus (CTI)
      ablation remains a significant problem. The prevalence of low contact force (CF)
      during CTI ablation using standard tools is unknown. Our aim was to characterize
      the prevalence of low CF applications when experienced operators performed CTI
      ablation using "traditional" markers of contact blinded to CF measurements.
      METHODS AND RESULTS: Average CF (grams, g) and force-time integral (FTI) was
      analyzed in 458 lesions in 17 patients undergoing CTI ablation. The isthmus was
      divided into the annular, mid and caval segments for region-specific analysis.
      Despite "good" contact using traditional markers, there was significant
      variability in CF within each isthmus segment (e.g., annular CTI 1-57 g). A high
      proportion of lesions had a CF <10 g (40%). Lowest CF was the annular (median 9
      g), followed by the mid (12 g) and the caval CTI (18 g, P < 0.001). Sites of
      acute CTI re-connection had a lower average CF and FTI than nonreconnected sites
      (P < 0.05). Each 1 g increase in CF was associated with a 16% reduction in risk
      of recovered CTI conduction (95% confidence interval: 4-27%, P = 0.01).
      CONCLUSION: Use of surrogate markers of "good contact" during ablation by
      experienced operators in the absence of real-time CF sensing resulted in nearly
      half of all lesions being delivered with low CF with marked region-specific
      variability in CF. Low CF was implicated in longer time to achieve conduction
      block and increased risk of acute reconnection. These findings underscore the
      importance of real-time CF measurements for optimizing ablation of typical atrial
      flutter.

PMID- 25952767
TI  - Establishment of a cell line from the ash and privet borer beetle Tylonotus
      bimaculatus Haldeman and assessment of its sensitivity to diacylhydrazine
      insecticides.
AB  - A novel cell line, NRCAN-Tb521, was developed from larvae of the longhorn beetle
      Tylonotus bimaculatus (Coleoptera: Cerambycidae), a pest of North American ash
      trees. The cell line has been successfully passaged more than 50 times and
      displayed very strong attachment to the substrate and a modal chromosomal count
      distribution of 19. Sequencing of a 649 bp fragment of the mitochondrial
      cytochrome oxidase I gene confirmed the identity of NRCAN-Tb521 as T.
      bimaculatus. The response of the cell line to 20-hydroxyecdysone and
      diacylhydrazine ecdysone agonist insecticides was also studied. At 10(-6) M, 20
      hydroxyecdysone, tebufenozide, methoxyfenozide and halofenozide triggered the
      production of numerous filamentous cytoplasmic extensions, and the cells tended
      to form aggregates, indicative of a cell differentiation response. This response
      was followed by a strong decrease in viability after 4 d. Reverse transcription
      polymerase chain reaction (PCR) experiments and sequencing of PCR fragments
      showed that the 20E receptor gene EcR is expressed in the cells and that 20E,
      tebufenozide, methoxyfenozide and halofenozide also induce the expression of the
      nuclear hormone receptor gene HR3. This report establishes that NRCAN-Tb521 is a
      valuable in vitro model to study effects of ecdysone agonists in wood-boring
      cerambycids.

PMID- 25952769
TI  - In vivo biological response to highly cross-linked and vitamin e-doped
      polyethylene--a particle-Induced osteolysis animal study.
AB  - Polyethylene particle-induced osteolysis is the primary limitation in the long
      term success of total joint replacement with conventional ultra high molecular
      weight polyethylene (UHMWPE). Highly cross-linked polyethylene (HXLPE) and
      vitamin E-doped cross-linked polyethylene (VE-HXLPE) have been developed to
      increase the wear resistance of joint surfaces. However, very few studies have
      reported on the incidence of particle-induced osteolysis for these novel
      materials. The aim of this study was to use a particle-induced osteolysis animal
      model to compare the in vivo biological response to different polymer particles.
      Three commercially available polymers (UHMWPE, HXLPE, and VE-HXLPE) were
      compared. Osseous properties including the bone volume relative to the tissue
      volume (BV/TV), trabecular thickness (Tb. Th), and bone mineral density (BMD)
      were examined using micro computed tomography. Histological analysis was used to
      observe tissue inflammation in each group. This study demonstrated that the
      osseous properties and noticeable inflammatory reactions were obviously decreased
      in the HXLPE group. When compared with the sham group, a decrease of 12.7% was
      found in BV/TV, 9.6% in BMD and 8.3% in Tb.Th for the HXLPE group. The heightened
      inflammatory response in the HXLPE group could be due to its smaller size and
      greater amount of implanted particles. Vitamin E diffused in vivo may not affect
      the inflammatory and osteolytic responses in this model. The morphological size
      and total cumulative amount of implanted particles could be critical factors in
      determining the biological response.

PMID- 25952768
TI  - Self-Reported HIV and HCV Screening Rates and Serostatus Among Substance Abuse
      Treatment Patients.
AB  - Substance users are at increased risk for HIV and HCV infection. Still, many
      substance use treatment programs (SUTP) fail to offer HIV/HCV testing. The
      present secondary analysis of screening data from a multi-site randomized trial
      of rapid HIV testing examines self-reported HIV/HCV testing patterns and
      serostatus of 2473 SUTP patients in 12 community-based sites that had not
      previously offered on-site testing. Results indicate that most respondents
      screened for the randomized trial tested more than a year prior to intake for HIV
      (52 %) and HCV (38 %). Prevalence rates were 3.6 and 30 % for HIV and HCV,
      respectively. The majority of participants that were HIV (52.2 %) and HCV
      positive (40.5 %) reported having been diagnosed within the last 1-5 years.
      Multivariable logistic regression showed that members of high-risk groups were
      more likely to have tested. Bundled HIV/HCV testing and linkage to care issues
      are recommended for expanding testing in community-based SUTP settings.

PMID- 25952771
TI  - Do Muscle Characteristics on Lumbar Spine Magnetic Resonance Imaging or Computed
      Tomography Predict Future Low Back Pain, Physical Function, or Performance? A
      Systematic Review.
AB  - OBJECTIVE: To determine whether lumbar muscle characteristics on magnetic
      resonance imaging (MRI) or computed tomography (CT) can inform clinicians as to
      the course of future low back pain (LBP), functional limitations, or physical
      performance, in adults with or without LBP. TYPE: Systematic review. LITERATURE
      REVIEW: We searched PubMed, Embase, and CINAHL through October 2014 for articles
      published in English in which authors assessed lumbar muscle characteristics on
      conventional MRI/CT as predictors of future LBP, functional limitations, or
      physical performance in adults. Studies with only postsurgical subjects were
      excluded. Our search identified 3554 articles, of which 6 observational cohort
      studies were included in the final review. METHODOLOGY: We used the Newcastle
      Ottawa Scale to evaluate potential bias. Data were extracted on study design,
      study population, sample size, participant characteristics, details of MRI/CT
      assessments, interventions, study outcomes, analysis methods, and study results.
      Because of heterogeneity between studies, we conducted a qualitative evidence
      synthesis. SYNTHESIS: Among high-quality studies, there was limited evidence
      that, for individuals with or without LBP, greater MRI-detected multifidus cross
      sectional area at L5-S1 predicted greater LBP intensity at 1-year follow-up,
      lesser erector spinae fat infiltration (FI) at L5-S1 predicted greater LBP
      intensity at 15-year follow-up, and greater erector spinae side-to-side FI
      asymmetry at L3-L4 predicted lower LBP frequency at 15-year follow-up; however,
      there was also limited evidence that all other MRI-detected paraspinal muscle
      characteristics examined were not predictive of LBP incidence, prevalence,
      frequency, or intensity at follow-up durations ranging from 1 to 15 years. There
      was limited evidence that greater CT-detected trunk muscle FI predicted worse
      physical performance in older adults at 3-year follow-up, but that trunk muscle
      cross-sectional area did not. CONCLUSION: Few lumbar muscle characteristics have
      limited evidence for an association with future LBP and physical performance
      outcomes, and the vast majority have limited evidence for having no association
      with such outcomes.

PMID- 25952770
TI  - miR-638 is a new biomarker for outcome prediction of non-small cell lung cancer
      patients receiving chemotherapy.
AB  - MicroRNAs (miRNAs), a class of small non-coding RNAs, mediate gene expression by
      either cleaving target mRNAs or inhibiting their translation. They have key roles
      in the tumorigenesis of several cancers, including non-small cell lung cancer
      (NSCLC). The aim of this study was to investigate the clinical significance of
      miR-638 in the evaluation of NSCLC patient prognosis in response to chemotherapy.
      First, we detected miR-638 expression levels in vitro in the culture supernatants
      of the NSCLC cell line SPC-A1 treated with cisplatin, as well as the apoptosis
      rates of SPC-A1. Second, serum miR-638 expression levels were detected in vivo by
      using nude mice xenograft models bearing SPC-A1 with and without cisplatin
      treatment. In the clinic, the serum miR-638 levels of 200 cases of NSCLC patients
      before and after chemotherapy were determined by quantitative real-time PCR, and
      the associations of clinicopathological features with miR-638 expression patterns
      after chemotherapy were analyzed. Our data helped in demonstrating that cisplatin
      induced apoptosis of the SPC-A1 cells in a dose- and time-dependent manner
      accompanied by increased miR-638 expression levels in the culture supernatants.
      In vivo data further revealed that cisplatin induced miR-638 upregulation in the
      serum derived from mice xenograft models, and in NSCLC patient sera, miR-638
      expression patterns after chemotherapy significantly correlated with lymph node
      metastasis. Moreover, survival analyses revealed that patients who had increased
      miR-638 levels after chemotherapy showed significantly longer survival time than
      those who had decreased miR-638 levels. Our findings suggest that serum miR-638
      levels are associated with the survival of NSCLC patients and may be considered a
      potential independent predictor for NSCLC prognosis. 

PMID- 25952772
TI  - Symmetry of electromechanical delay, peak torque and rate of force development in
      knee flexors and extensors in female and male subjects.
AB  - PURPOSE: The aim of the study was to evaluate electromechanical delay (EMD), peak
      torque (PT) and rate of force development (RFD) in selected muscles of right and
      left lower extremities in groups of female and male subjects. METHODS: The study
      evaluated 9 volunteer female subjects (mean +/- SD: age: 21.67 +/- 0.87 years;
      height: 168 +/- 7 cm; body mass: 59.44 +/- 4.8 kg) and 10 male university
      students (mean +/- SD: age 22 +/- 1.25 years; height: 179 +/- 6 cm; body mass:
      74.3 +/- 5.1 kg) from the Faculty of Physical Education. Muscle torques and
      electromyographic activity were measured for knee flexors and extensors in static
      conditions, separately for the right and the left lower extremities. During the
      measurements, the subjects generated the maximum torque as fast as possible.
      Surface electrodes were placed on the right and left lower extremities on the
      following muscles: rectus femoris, vastus lateralis (m.VL), vastus medialis and
      biceps femoris. RESULTS: Symmetry of EMD, RFD and "flexors-extensors" ratio was
      found in the muscles of the right and left lower extremities (with an exception
      of m.VL) in the group of male and female subjects. Statistical analysis
      demonstrated the presence of asymmetry in PT (297.66 vs. 272.05 N?m) and relative
      force in knee extensors in the group of men (3.90 vs. 3.54 N?m?kg-1).
      CONCLUSIONS: Symmetry of EMD and asymmetry of PT might suggest that the cause of
      asymmetry of the muscular force is mainly morphologi- cal characteristics of the
      muscle rather than the process of controlling its activity.

PMID- 25952773
TI  - Composition, antimicrobial, antioxidant, and antiproliferative activity of
      Origanum dictamnus (dittany) essential oil.
AB  - BACKGROUND: Nowadays, there has been an increased interest in essential oils from
      various plant origins as potential antimicrobial, antioxidant, and
      antiproliferative agents. This trend can be mainly attributed to the rising
      number and severity of food poisoning outbreaks worldwide along with the recent
      negative consumer perception against artificial food additives and the demand for
      novel functional foods with possible health benefits. Origanum dictamnus
      (dittany) is an aromatic, tender perennial plant that only grows wild on the
      mountainsides and gorges of the island of Crete in Greece. OBJECTIVE: The aim of
      the present study was to investigate the antimicrobial, antioxidant, and
      antiproliferative properties of O. dictamnus essential oil and its main
      components and assess its commercial potential in the food industry. DESIGN: O.
      dictamnus essential oil was initially analyzed by gas chromatography-mass
      spectrometry (GC-MS) to determine semi-quantitative chemical composition of the
      essential oils. Subsequently, the antimicrobial properties were assayed and the
      minimum inhibitory and non-inhibitory concentration values were determined. The
      antioxidant activity and cytotoxic action against the hepatoma adenocarcinoma
      cell line HepG2 of the essential oil and its main components were further
      evaluated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and by the
      sulforhodamine B (SRB) assay, respectively. RESULTS: The main constituents of O.
      dictamnus essential oil identified by GC-MS analysis were carvacrol (52.2%),
      gamma-terpinene (8.4%), p-cymene (6.1%), linalool (1.4%), and caryophyllene
      (1.3%). O. dictamnus essential oil and its main components were effective against
      Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Listeria
      monocytogenes, Salmonella Enteritidis, Salmonella typhimurium, Saccharomyces
      cerevisiae, and Aspergillus niger. In addition, the estimated IC50 value for the
      DPPH radical scavenging activity for O. dictamnus essential oil was 0.045+/
      0.0042% (v/v) and was mainly attributed to carvacrol. The EC50 value for the
      essential oil in the 72h SRB assay in HepG2 cells was estimated to be 0.0069+/
      0.00014% (v/v). Among the individual constituents tested, carvacrol was the most
      bioactive compound and accounted for the observed antiproliferative activity of
      the essential oil. CONCLUSIONS: The results revealed that O. dictamnus essential
      oil is a noteworthy growth inhibitor against the microbes studied. It also
      possesses significant antioxidant activity and demonstrated excellent
      cytotoxicity against HepG2 cells. Taken together, O. dictamnus essential oil may
      represent an effective and inexpensive source of potent natural antimicrobial
      agents with health-promoting properties, which may be incorporated in food
      systems.

PMID- 25952774
TI  - Emphysema and DLCO predict a clinically important difference for 6MWD decline in
      COPD.
AB  - BACKGROUND: Exercise impairment is a central feature of chronic obstructive
      pulmonary disease (COPD), and a minimal clinically important difference (MCID)
      for 6-min walk distance (6MWD) decline (>30 m) has been associated with increased
      mortality. The predictors of the MCID are not fully known. We hypothesize that
      physiological factors and radiographic measures predict the MCID. METHODS: We
      assessed 121 COPD subjects during 2 years using clinical variables, computed
      tomographic (CT) measures of emphysema, and functional measures including
      diffusion lung capacity for carbon monoxide (DLCO). The association between an
      MCID for 6MWD and clinical, CT, and physiologic predictors was assessed using
      logistic analysis. The C-statistic was used to assess the predictive ability of
      the models. RESULTS: Forty seven (39%) subjects had an MCID. In an imaging-based
      model, log emphysema and age were the best predictors of MCID (emphysema Odds
      Ratio [OR] 2.47 95%CI [1.28-4.76]). In a physiologic model, DLCO, age, and male
      gender were selected the best predictors (DLCO OR 1.19 [1.08-1.31]). The C
      statistic for the ability of these models to predict an MCID was 0.71 and 0.75,
      respectively. CONCLUSION: In COPD patients the burden of emphysema on CT scan and
      DLCO predict a clinically meaningful decline in exercise capacity.

PMID- 25952775
TI  - Dynamics of appetite-mediated gene expression in daidzein-fed female rats in the
      meal-feeding method.
AB  - We previously found that daidzein decreased food intake in female rats. The
      present study aimed to elucidate the relationship between dynamics of appetite
      mediated neuropeptides and the anorectic effect of daidzein. We examined appetite
      mediated gene expression in the hypothalamus and small intestine during the 3
      meals per day feeding method. Daidzein had an anorectic effect specifically at
      the second feeding. Neuropeptide-Y (NPY) and galanin mRNA levels in the
      hypothalamus were significantly higher after feeding in the control but not in
      the daidzein group, suggesting that daidzein attenuated the postprandial increase
      in NPY and galanin expression. The daidzein group had higher corticotrophin
      releasing hormone (CRH) mRNA levels in the hypothalamus after feeding, and
      increased cholelcystokinin (CCK) mRNA levels in the small intestine, suggesting
      that CCK is involved in the hypothalamic regulation of this anorectic effect.
      Therefore, daidzein may induce anorexia by suppressing expression of NPY and
      galanin and increasing expression of CRH in the hypothalamus.

PMID- 25952776
TI  - Immunotherapy for ovarian cancer: what are the targets of the future?

PMID- 25952777
TI  - Personalization of loco-regional care for primary breast cancer patients (part
      1).
AB  - ABSTRACT  Kyoto Breast Cancer Consensus Conference, Kyoto, Japan, 18-20 February
      2014 The loco-regional management of breast cancer is increasingly complex with
      application of primary systemic therapies, oncoplastic techniques and genetic
      testing for breast cancer susceptibility. Personalization of loco-regional
      treatment is integral to optimization of breast cancer care. Clinical and
      pathological tumor stage, biological features and host factors influence loco
      regional treatment strategies and extent of surgical procedures. Key issues
      including axillary staging, axillary treatment, radiation therapy, primary
      systemic therapy (PST), preoperative hormonal therapy and genetic predisposition
      were identified and discussed at the Kyoto Breast Cancer Consensus Conference
      (KBCCC2014). In the first of a two part conference scene, consensus
      recommendations for axillary management are presented and focus on the following
      topics: indications for completion axillary lymph node dissection in primary
      surgical patients with <=2 macrometastases or any sentinel nodal deposits after
      PST; the timing of sentinel lymph node biopsy in the context of PST; use of
      axillary irradiation as a component of primary treatment plans and the role of
      intraoperative node assessment in the post-Z0011 era. 

PMID- 25952778
TI  - Personalization of loco-regional care for primary breast cancer patients (part
      2).
AB  - Kyoto Breast Cancer Consensus Conference, Kyoto, Japan, 18-20 February 2014 The
      loco-regional management of breast cancer is increasingly complex with
      application of primary systemic therapies, oncoplastic techniques and genetic
      testing for breast cancer susceptibility. Personalization of loco-regional
      treatment is integral to optimization of breast cancer care. Clinical and
      pathological tumor stage, biological features and host factors influence loco
      regional treatment strategies and extent of surgical procedures. Key issues
      including axillary staging, axillary treatment, radiation therapy, primary
      systemic therapy (PST), preoperative hormonal therapy and genetic predisposition
      were identified and discussed at the Kyoto Breast Cancer Consensus Conference
      (KBCCC2014). In the second of a two part conference scene, consensus
      recommendations for radiation treatment, primary systemic therapies and
      management of genetic predisposition are reported and focus on the following
      topics: influence of both clinical response to PST and stage at presentation on
      recommendations for postmastectomy radiotherapy; use of regional nodal
      irradiation in selected node-positive patients and those with adverse
      pathological factors; extent of surgical resection following downstaging of
      tumors with PST; use of preoperative hormonal therapy in premenopausal women with
      larger, node-negative luminal A-like tumors and managing increasing demands for
      contralateral prophylactic mastectomy in patients with a unilateral sporadic
      breast cancer.

PMID- 25952779
TI  - A review of rituximab, the first anti-CD20 monoclonal antibody used in the
      treatment of B non-Hodgkin's lymphomas.
AB  - Rituximab is a type I anti-CD20 monoclonal antibody, which stabilizes CD20 on
      lipid rafts, promoting antibody-dependent cellular cytotoxicity and complement
      dependent cytotoxicity activities. It is the first targeted therapy used in B
      cell malignancies and has revolutionized their treatment, without excess of
      toxicity. In combination with chemotherapy, it has significantly improved
      response rates and progression-free survival and, for some of them, overall
      survival of patients with diffuse large B-cell lymphoma, follicular lymphoma,
      marginal zone lymphoma, mantle cell lymphoma. Moreover, it has been shown to
      improve progression-free survival in maintenance in follicular lymphoma as well
      as mantle cell lymphoma. Improvement of its efficacy includes exploration of
      resistance mechanisms, pharmacokinetics parameters, role of vitamin D and
      evaluation of subcutaneous route, among others.

PMID- 25952780
TI  - (90)Y-glass microspheres for hepatic neoplasia.
AB  - Unresectable liver cancer presents a major problem in the treatment of solid
      tumors. Transarterial radioembolization is a modern approach toward primary and
      secondary liver malignancies. The mechanism of action is independent from other
      therapies that are based on ischemia or chemotoxicity. (90)Y-resin and (90)Y
      glass microspheres are commercially available for transarterial
      radioembolization. Available data on the use of (90)Y-glass microspheres in
      hepatocellular carcinoma and metastatic disease indicate that this treatment is
      safe and effective. In hepatocellular carcinoma the results compare well with
      chemoembolization and might be considered more often. Current data in metastatic
      disease are promising, but there is a strong need for prospective randomized
      trials to identify the role of transarterial radioembolization with (90)Y-glass
      microspheres in metastatic liver disease.

PMID- 25952781
TI  - Vemurafenib in BRAFV600 mutated metastatic melanoma: a subanalysis of the Italian
      population of a global safety study.
AB  - AIM: We describe the ad interim analysis of the Italian cohort of the global
      safety study on vemurafenib in patients with metastatic melanoma. PATIENTS &
      METHODS: A total of 385 patients received vemurafenib 960 mg twice daily.
      RESULTS: In total, 330 patients (86%) reported adverse events; 16 serious adverse
      events were observed (three related to vemurafenib). The response rate was 30.4%.
      Median progression-free survival (PFS) and overall survival (OS) were 5.9 months
      and 16.3 months, respectively. In patients with brain metastasis (BM; n = 83),
      median PFS was 4.3 months and OS was 7.6 months. In patients without BM, PFS was
      6.5 months and OS was not reached. Median PFS was 12.6 months in patients with
      M1a stage of disease, 9.6 months in those with M1b stage and 5.4 months in
      subjects with M1c stage. CONCLUSION: Vemurafenib appears safe and active in
      clinical practice, and seems particularly active in patients without BM and low
      tumor burden.

PMID- 25952782
TI  - Human papillomavirus confers radiosensitivity in cancer cervix: a hypothesis
      toward a possible restoration of apoptotic pathways based on clinical outcomes.
AB  - AIM: To evaluate if high baseline local human papillomavirus (HPV) titer confers
      radiosensitivity in cancer cervix. A hypothesis is proposed to explain the
      clinical outcomes. MATERIALS & METHODS: 121 serial HPV titers from cervical
      smears of 21 patients were estimated during radiotherapy (RT) and correlated with
      RT dose-response curves, local response and local disease-free survival (LDFS).
      RESULTS: Local response (p = 0.04) and LDFS (p = 0.06) were better in high HPV
      than low HPV baseline group. On multivariate analysis, RT doses for 50% tumor
      regression and baseline HPV titer were the only predictors for LDFS. CONCLUSION:
      Serial reductions of HPV titers following RT could restore the HPV induced
      temporarily downregulated p53 and pRb apoptotic pathways resulting in
      radiosensitivity of these tumors.

PMID- 25952783
TI  - Targeting FGF receptors in colorectal cancer: from bench side to bed side.
AB  - Successful management of advanced colorectal cancer has been a challenging job
      for practicing oncologists as well as a priority for the oncology research
      community. The better understanding of the underlying patho-biology and critical
      pathway targets in this disease has contributed to major developments in that
      direction. In this review, we will revise the different biological and clinical
      aspects related to the use of FGFR pathway-targeted therapies in advanced
      colorectal cancer with particular focus on future perspectives in that regard.

PMID- 25952784
TI  - Present and future of personalized medicine in adult genitourinary tumors.
AB  - The development of targeted agents has completely revolutionized the therapeutic
      scenario of genitourinary tumors. However, no biomarkers of tumor response or
      patient tolerability have been validated so far, and the selection of patients
      who may benefit from these approaches is still empirical. Significant advances in
      genomic sequencing and molecular characterization of these tumors have allowed
      identification of complex genomic abnormalities, thus increasing our knowledge on
      cancer biological landscapes and paving the way to the development of
      personalized strategies based on the patient's genomic and cancer's molecular
      profiles. This review is an overview of recent findings and emerging
      individualized therapies in patients with prostate, renal and bladder cancer,
      focusing on the promises and limitations of this approach in this setting.

PMID- 25952785
TI  - Molecular pathogenesis of ovarian clear cell carcinoma.
AB  - Ovarian clear cell carcinoma is a distinct subtype of epithelial ovarian cancer,
      characterized by an association with endometriosis, glycogen accumulation and
      resistance to chemotherapy. Key driver events, including ARID1A mutations and
      HNF1B overexpression, have been recently identified and their functional
      characterization is ongoing. Additionally, the role of glycogen in promoting the
      malignant phenotype is coming under scrutiny. Appreciation of the notion that
      ovarian clear cell carcinoma is essentially an ectopic uterine cancer will
      hopefully lead to improved animal models of the disease, in turn paving the way
      for effective treatments.

PMID- 25952786
TI  - Molecular targets in glioblastoma.
AB  - Glioblastoma is the most lethal brain tumor. The poor prognosis results from lack
      of defined tumor margins, critical location of the tumor mass and presence of
      chemo- and radio-resistant tumor stem cells. The current treatment for
      glioblastoma consists of neurosurgery, followed by radiotherapy and temozolomide
      chemotherapy. A better understanding of the role of molecular and genetic
      heterogeneity in glioblastoma pathogenesis allowed the design of novel targeted
      therapies. New targets include different key-role signaling molecules and
      specifically altered pathways. The new approaches include interference through
      small molecules or monoclonal antibodies and RNA-based strategies mediated by
      siRNA, antisense oligonucleotides and ribozymes. Most of these treatments are
      still being tested yet they stay as solid promises for a clinically relevant
      success.

PMID- 25952787
TI  - Vismodegib in the treatment of basal cell carcinoma: indications for clinical
      practice.
AB  - Basal cell carcinoma (BCC) is a frequent skin cancer which can cause substantial
      morbidity due to its location on the face, its frequency of relapse and its
      capacity to invade local tissues. The primary treatment of BCC usually involves
      surgery or radiotherapy. In patients who have exhausted surgical and radiotherapy
      options or with metastatic BCC, guidelines recommend the use of the Hedgehog
      pathway inhibitor vismodegib. This molecule is indicated for the treatment of
      adults with metastatic BCC, or with locally advanced BCC which has recurred
      following surgery or who are not eligible to surgery or radiation. This paper
      aims to provide suggestions on the optimal management of BCC patients treated
      with vismodegib in clinical practice, according to the large experience gained by
      a group of Italian dermatologists and oncologists. In particular, the focus of
      this paper will be on the monitoring of patients and the management of adverse
      events.

PMID- 25952789
TI  - Erratum.

PMID- 25952790
TI  - Erratum.

PMID- 25952788
TI  - Kidney cancer and 2014: is innovation really over?
AB  - 2014 has been a year of significant innovations on kidney cancer treatments, the
      most relevant of which will be shown below. In particular, we analyzed the
      consolidated knowledge regarding the role of surgery in localized and advanced
      renal cell carcinoma and the targeted therapies already approved for metastatic
      renal cell carcinoma. Furthermore, we examined the outstanding issues, with
      particular reference to the choice of the second-line and the role of adjuvant
      and neoadjuvant treatments. Finally, we outlined the future therapeutic
      perspectives and those definitely abandoned.

PMID- 25952792
TI  - Erratum.

PMID- 25952791
TI  - Erratum.

PMID- 25952793
TI  - Condensed tannins increase nitrogen recovery by trees following insect
      defoliation.
AB  - While the importance of plant secondary metabolites to belowground functioning is
      gaining recognition, the perception remains that secondary metabolites are
      produced for herbivore defense, whereas their belowground impacts are ecological
      by-products, or 'afterlife' effects. However, plants invest a significant amount
      of resources into production of secondary metabolites that have minimal effects
      on herbivore resistance (e.g. condensed tannins and insect herbivores). We show
      that genetically mediated variation in condensed tannin concentration is
      correlated with plant nitrogen recovery following a severe defoliation event. We
      used single-tree mesocosms labeled with (15) N to track nitrogen through both the
      frass and litter cycling pathways. High concentrations of leaf tannins in Populus
      tremuloides were correlated with (15) N recovery from frass within the same
      growing season and in the following growing season. Likewise, leaf tannin
      concentrations were also correlated with (15) N recovery from the litter of
      defoliated trees in the growing season following the defoliation event.
      Conversely, tannins were not well correlated with nitrogen uptake under
      conditions of nominal herbivory. Our results suggest that tannins may confer
      benefits in response to herbivore pressure through conserved belowground nitrogen
      cycling, rather than via defensive properties. Consequently, tannins may be
      considered as chemical mediators of tolerance rather than resistance. 

PMID- 25952794
TI  - [Leucoderma in children: Review of the literature].
AB  - BACKGROUND: Leucoderma is a frequent presenting complaint in children and it is
      sometimes difficult to make a definite diagnostic during the first consultation.
      The aim of this study is to analyse the diagnoses associated with leucoderma in
      children in order to propose a practical approach to their differential
      diagnosis. MATERIAL AND METHODS: We performed a review of the literature using
      the keywords "leucoderma children review", "leucoderma Ito" and "nevus
      depigmentosus" in the Medline database. All relevant articles were included.
      RESULTS: Four hundred and thirty-five articles were retrieved and 179 were
      analysed. A clinical approach was proposed in 6 articles and investigations in 15
      articles. DISCUSSION: Causal diagnosis of leucoderma may frequently be made on
      clinical grounds by determining the age of onset and distribution of lesions.
      Nevertheless, some situations require investigation. The literature is limited
      regarding clinical approaches and examinations in leucoderma. Herein, we present
      a systematic clinical and laboratory approach to the differential diagnosis of
      these skin disorders.

PMID- 25952795
TI  - A proof of concept trial of the anti-EGFR antibody mixture Sym004 in patients
      with squamous cell carcinoma of the head and neck.
AB  - PURPOSE: The purpose of the trial was to assess the efficacy and tolerability of
      Sym004, a novel 1:1 mixture of two chimeric monoclonal antibodies (992 and 1024)
      targeting non-overlapping epitopes of the anti-epidermal growth factor receptor
      (EGFR), in patients with squamous cell carcinoma of the head and neck (SCCHN).
      METHODS: Incurable, recurrent and/or metastatic SCCHN patients with acquired
      resistance to anti-EGFR monoclonal antibody-containing treatment received weekly
      infusions of 12 mg/kg Sym004 until disease progression or unacceptable toxicity.
      RESULTS: Among the 26 patients treated with Sym004, the proportion of patients
      alive without disease progression at 6 months was 12 % (95 % CI 1-39 %). The
      median duration of progression-free survival was 82 days (95 % CI 41-140 days).
      Of 19 patients evaluable for response, eight showed a decrease in the sum of the
      largest diameter in their target lesions (median 11 %; range 7-27 %). The best
      overall response was stable disease in 13 patients (50 %). Paired biopsies showed
      a significant down-regulation of EGFR in both skin and tumors following exposure
      to Sym004. All patients had EGFR-related adverse events, including grade 3 skin
      toxicities and grade >=3 hypomagnesemia reported in 13 (50 %) and 10 (38 %) of 26
      patients, respectively. One event fulfilling the protocol-defined criteria for
      infusion-related reactions (grade 2) was reported. No anti-drug antibodies were
      detected. CONCLUSIONS: The marked EGFR down-regulation shown in target tissues
      supports the proposed mechanism of action of Sym004. This trial revealed modest
      anti-tumor activity of Sym004 in extensively pretreated advanced SCCHN patients.

PMID- 25952796
TI  - Sandwich-like neoadjuvant therapy with bevacizumab for locally advanced rectal
      cancer: a phase II trial.
AB  - PURPOSE: Current neoadjuvant chemoradiotherapy had limited impact on distal
      metastasis and survival in locally advanced rectal cancer. Here, we investigated
      a new sandwich-like neoadjuvant regimen with bevacizumab. METHODS: This was a
      single-arm, open-labeled, phase II trial. Patients with locally advanced rectal
      cancer received sandwich-like neoadjuvant therapy with bevacizumab (induction
      therapy with bevacizumab and FOLFOX, concurrent chemoradiotherapy with
      bevacizumab and consolidation chemotherapy with FOLFOX). Surgery was performed 4
      6 weeks later. The primary endpoint of this study was pathologic complete
      response. RESULTS: Twenty-five eligible patients were included. All completed the
      neoadjuvant therapy protocol. During the course of neoadjuvant therapy, 3
      patients (12 %) had grade 4 hematological toxicity events and 12 (48 %) had grade
      3 non-hematological toxicity events. According to RECIST criteria, 18 patients
      (72 %) achieved partial response and the rest seven patients (28 %) remained
      stable disease. Two patients (8 %) refused the subsequent surgical therapy for
      personal reasons, and 23 patients (92 %) underwent operations finally. Nine (39.1
      %, 95 % CI 18.0-57.5 %) of them achieved pathologic complete response. Five of
      them (21.7 %) had postoperative complications. After a median follow-up period of
      25.3 (14.4-40.9) months, four patients developed disease progression and two died
      of cancer. The 3-year overall survival rate was 95 % (95 % CI 69.5-99.3 %), and
      the 3-year disease-free survival rate was 72.5 % (95 % CI 33.7-90.9 %).
      CONCLUSIONS: Sandwich-like neoadjuvant therapy with bevacizumab is safe and
      effective for locally advanced rectal cancer.

PMID- 25952797
TI  - CDC report confirms "Hispanic paradox".

PMID- 25952798
TI  - Quo vadis, NICE?

PMID- 25952799
TI  - Accuracy for optical diagnosis of colorectal polyps in clinical practice.
AB  - BACKGROUND: Optical diagnostic involves predicting polyp histopathology from its
      endoscopic characteristics. It is only recommended for diminutive polyps ( < or =
      5 mm) and for predictions made with high confidence. OBJECTIVES: To evaluate the
      accuracy of optical imaging in clinical practice and to assess if optical
      diagnosis is useful for predicting future colonoscopy surveillance intervals
      without waiting for histopathological analysis. METHODS: consecutive > 18 years
      patients were enrolled in this prospective study. Colonoscopies were performed by
      five expert endoscopists who previously participated in an ex-vivo training.
      Colonoscopes CF-H180AL and CF-Q180AL were used together with Exera II (Olympus
      Medical System, Tokyo, Japan) processors. Each polyp was characterized in real
      time using white light and Narrow Band Imaging. Accuracy of optical diagnosis (S,
      E, NPV, PPV) and correlation between surveillance interval based on optical
      diagnosis and histopathological analysis were calculated. RESULTS: 311 colon
      polyps < 10 mm (216 diminutive) in 195 patients were analyzed. Accuracy of
      optical diagnostics for predictions made with high confidence: Diminutive
      polyps(sensitivity 0.59, specificity 0.92, NPV 0.48); polyps < 10 mm (sensitivity
      0.73, specificity 0.88, NPV 0.50). An optical diagnosis based surveillance
      recommendation was given to 90 patients. Concordance with histopathology based
      recommendation was 92.2% according to the European guideline and 93.3% according
      to the ESGE guideline. CONCLUSIONS: Optical diagnostics can be used to predict
      future surveillance intervals immediately after colonoscopy. However, in this
      study, based on clinical practice, the accuracy of optical imaging is below the
      recommended standards.

PMID- 25952800
TI  - The predictive capacity of the Glasgow-Blatchford score for the risk
      stratification of upper gastrointestinal bleeding in an emergency department.
AB  - OBJECTIVES: To assess the ability of the Glasgow Blatchford Score (GBS) system to
      identify the need for urgent upper gastrointestinal endoscopy (UGIE) in patients
      with upper gastrointestinal bleeding (UGIB). METHODS: An observational,
      retrospective study was carried out in all patients attended at the ER for
      suspected UGIB in one year. Patients were split into two categories -high-risk
      (>2) and low-risk ( < or = 2)- by means of the GBS system. RESULTS: A total of 60
      patients were included. Of these, 46 were classified as "high-risk" (> 2) and 14
      as "low-risk" ( < or = 2) subjects.The characteristics of patients in the low
      risk group included: Mean age: 46.6 +/- 13.7 (18-88) years. Males/females: 7/7.
      Urgent endoscopy revealed: normal (50%; n = 7); esophagitis (21.4%; n = 3);
      gastritis (14.2%; n = 2); Mallory-Weiss syndrome (7.1%; n = 1); non-bleeding
      varices (7.1%; n = 1). The characteristics of patients in the high-risk group
      included: Mean age: 68.7 +/- 19.8 (31-91) years. Males/females: 30/16. Digestive
      endoscopy revealed: Gastric/duodenal ulcer (56.52%; n = 26); normal (17.39%; n =
      8); esophagitis (8.69%; n = 4); gastritis (8.69%; n = 4); angioectasia (4.34%; n
      = 2); bleeding varices (4.34%; n = 2). Low-risk patients exhibited no lesions
      requiring urgent management during endoscopy, and the sensitivity of the GBS
      scale for high-risk UGIB detection was found to be 100% (95% CI: 86.27%, 99.71%),
      with a specificity of 48.28% (95% CI: 29.89, 67.1%). CONCLUSIONS: The GBS scale
      seems to accurately identify patients with low-risk UGIB, who may be managed on
      an outpatient basis and undergo delayed upper GI endoscopy at the outpatient
      clinic.

PMID- 25952801
TI  - A review of three educational projects using interactive theater to improve
      physician-patient communication when treating patients with irritable bowel
      syndrome.
AB  - BACKGROUND: Quality communication skills and increased multicultural sensitivity
      are universal goals, yet teaching them have remained a challenge for educators.
      OBJECTIVE: To document the process and participant responses to Interactive
      Theater when used as a method to teach physician/patient communication and cross
      cultural competency. DESIGN, SETTING, AND PARTICIPANTS: Three projects are
      reported. They were collaborations between Theater Delta, the UNC Center for
      Functional GI and Motility Disorders, the Rome Foundation, the World
      Gastroenterology Organization, and the American Gastroenterological Association.
      OUTCOME MEASURES: 8 forced choice and 6 open ended were collected from each
      participant using a post-performance evaluation form. RESULTS: Responses to the 8
      indicators relating to a positive experience participating in the Interactive
      Theater. The vast majority either agreed or strongly agreed with the statements
      on the evaluation form. Written comments explained why. CONCLUSIONS: Data
      indicates that Interactive Theater stimulates constructive dialogue, analysis,
      solutions, and intended behavior change with regard to communication skills and
      adapting to patients from multicultural backgrounds. Interactive Theater directly
      focuses on communication itself (active listening, empathy, recognizing cultural
      differences, etc.) and shows promise as an effective way to improve awareness and
      skills around these issues.

PMID- 25952803
TI  - Groove pancreatitis.
AB  - Groove pancreatitis is a type of chronic pancreatitis that affects the area
      between the pancreatic head, the duodenum and the common bile duct and can
      simulate, mask or coexist with pancreatic carcinoma. It should be considered in
      the differential diagnosis of pancreatic masses or duodenal stenosis. It is a
      rare disease but is probably underdiagnosed. Several names are used to refer to
      it in the literature, a fact that makes it difficult to extract precise
      information.Here we present an exhaustive review of the relevant literature on
      the entity and discuss its clinical features, diagnosis and therapy.

PMID- 25952802
TI  - Hypercontractile esophagus: Clinical context and motors findings in high
      resolution manometry.
AB  - BACKGROUND: Hypercontractile esophagus (HE) is a primary hypercontractile
      disorder of the esophageal musculature not frequently seen in the general
      population. It is characterized by the presence of at least one contraction with
      a very high amplitude and duration (DCI > 8,000 mmHg/s/cm) in patients with
      esophageal symptoms. The aim of our study was to assess the clinical context and
      manometric characteristics in patients with HE using highresolution manometry
      (HRM). METHODS: We thoroughly reviewed the clinical features and manometric
      findings of a total of 720 patients with esophageal symptoms that were attended
      in the Department of Gastroenterology of our hospital between June 2011 and June
      2013. RESULTS: We found seven patients that met criteria for HE according to the
      Chicago Classification (2012). All of the patients were women (100%). Mean age
      was 64 years old. Most frequent symptoms were: Chest pain, dysphagia and
      heartburn.In one patient (14%) the HE was related to a gastroesophageal reflux
      disease (GERD) and gastroesophageal junction (GEJ) outflow obstruction. Three
      patients (43%) had more than one hypercontractile contraction in the study. Four
      patient (57%) hade multipeaked pattern (Jackhammer esophagus) and y two of them
      were synchronized with respiration. Two patients (29%) were diagnosed with hiatus
      hernias. Integrated relaxation pressure (IRP) was not higher in hypercontractile
      contractions than in normal contractions. Only one patient presented a slight
      alteration of the relaxation (IRP-4s = 15 mmHg) with normal peristalsis, GEJ
      outflow obstruction and not multipeakeded pattern. One patient presented
      pathological acid exposure (PAE) in 24-hours pH-metry. CONCLUSIONS: HE is a rare
      disorder and HRM is essential for its correct diagnosis and characterization. The
      treatment of HE should achieve the disappearance or at least improvement of the
      patient's symptoms and avoid unnecessary diagnostic testing.

PMID- 25952804
TI  - Management of antithrombotic drugs in association with endoscopic procedures.
AB  - The use of antithrombotic drugs (anticoagulants and antiplatelets) has increased
      significantly with our understanding of cardiovascular risk. Encountering
      patients on these therapies who require an endoscopic procedure is therefore
      increasingly common. At decision making the endoscopist must rely on other
      specialists (basically cardiologists and hematologists) as risk not only lies
      among increased bleeding odds but also in the possibility of thrombosis following
      dose discontinuation or change. Understanding the pharmacology, indications, and
      risks of endoscopic procedures is therefore essential if sound decisions are to
      be made. The efforts of four scientific societies have been brought together to
      provide clinical answers on the use of antiplatelets and anticoagulants, as well
      as action algorithms and a practical protocol proposal for endoscopy units. 

PMID- 25952805
TI  - Endoscopic radiofrequency ablation for APC refractory gastric antral vascular
      ectasia using the HALO90 system in a kidney transplant candidate.

PMID- 25952806
TI  - Adenocarcinoma at the site of a terminal colostomy. A rare but important entity.

PMID- 25952807
TI  - Poorly differentiated early gastric adenocarcinoma of mixed type with "crawling"
      pattern of extension.

PMID- 25952808
TI  - Collagenous gastritis in the pediatric age.
AB  - Collagenous gastritis (CG) is an uncommon condition known in the pediatric age.
      It is characterized by the presence of subepithelial collagen bands (> 10 microm)
      associated with lymphoplasmacytic infiltration of the stomach's lamina propria.
      Symptoms manifested by patients with CG may be common with many other disorders.
      It typically manifests with epigastralgia, vomiting, and iron deficiency during
      pre-adolescence. This condition's pathophysiology remains unclear. In contrast to
      adults, where association with collagenous colitis and other autoimmune
      conditions is more common, pediatric involvement is usually confined to the
      stomach. Drugs of choice include proton pump inhibitors and corticoids. A case is
      reported of a 12-year-old girl with abdominal pain and ferritin deficiency who
      was diagnosed with CG based on gastric biopsy and experienced a favorable
      outcome.

PMID- 25952809
TI  - Epiphrenic and middle esophageal diverticula: A rare cause of esophageal
      dysphagia. Esophageal high resolution manometry findings.

PMID- 25952810
TI  - [Information for patients. Esophagitis induced by drugs].

PMID- 25952811
TI  - Knotting of Duodopa(r) duodenal infusion system.

PMID- 25952812
TI  - Sporadic neurofibroma on the esophagogastric junction. A case report.

PMID- 25952813
TI  - Induction of NKT cells after administration of a vaccine against rotavirus.

PMID- 25952814
TI  - Myeloid sarcoma of gastrointestinal tract: A rare cause of obstruction.

PMID- 25952815
TI  - Primary hepatic neuroendocrine tumor in a patient with acute HBV hepatitis: An
      unusual neoplasia.

PMID- 25952816
TI  - Treatment after iatrogenic colonoscopic perforation, is the laparoscopic approach
      a good option?

PMID- 25952817
TI  - Simultaneous determination of aflatoxin B1 and M1 in milk, fresh milk and milk
      powder by LC-MS/MS utilising online turbulent flow chromatography.
AB  - A novel, fully automated method based on dual-column switching using online
      turbulent flow chromatography followed by LC-MS/MS was developed for the
      determination of aflatoxin B1 and M1 in milk, fresh milk and milk powder samples.
      After ultrasound-assisted extraction, samples were directly injected into the
      chromatographic system and the analytes were concentrated on the clean-up loading
      column. Through purge switch, analytes were transferred to the analytical column
      for subsequent detection by mass spectrometry. Different types of TurboFlow(TM)
      columns, transfer flow rates and transfer times were optimised. Method limits of
      detection obtained for AFB1 and AFM1 were 0.05 MUg kg(-1), and limits of
      quantification were 0.1 MUg kg(-1). Recoveries of aflatoxin B1 and M1 were in
      range of 81.1-102.1% for all samples. Matrix effects of aflatoxin B1 and M1 were
      in range of 63.1-94.3%. The developed method was successfully used for the
      analysis of aflatoxin B1 and M1 in real samples.

PMID- 25952818
TI  - Platelet-Rich Plasma Intra-articular Knee Injections Show No Superiority Versus
      Viscosupplementation: A Randomized Controlled Trial.
AB  - BACKGROUND: Osteoarthritis (OA) is a common disease that will affect almost half
      the population at some point in their lives through pain and decreased functional
      capacity. New nonoperative options are being proposed to treat earlier stages of
      joint degeneration to provide symptomatic relief and delay surgical intervention.
      PURPOSE: To evaluate the benefit provided by platelet-rich plasma (PRP)
      injections to treat knee joint degeneration in comparison with hyaluronic acid
      (HA), the most common injective treatment currently adopted for this condition.
      STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total
      of 443 patients were screened, and 192 of them were enrolled in the study
      according to the following inclusion criteria: (1) unilateral symptomatic knee
      with history of chronic pain (at least 4 months) or swelling and (2) imaging
      findings of degenerative changes (Kellgren-Lawrence score of 0-3 at radiographs
      or MRI evidence of degenerative chondropathy). Patients underwent 3 weekly intra
      articular injections of either PRP or HA. Patients were prospectively evaluated
      at baseline and then at 2, 6, and 12 months of follow-up using the International
      Knee Documentation Committee (IKDC) subjective score (main outcome), Knee injury
      and Osteoarthritis Outcome Score, EuroQol visual analog scale, and Tegner score.
      Range of motion, transpatellar circumference, patient satisfaction, and adverse
      events were also recorded. RESULTS: Two patients reported severe pain and
      swelling after HA injections, while no major adverse events were noted in the PRP
      group. However, PRP presented overall significantly more postinjection swelling
      and pain. Both treatments proved to be effective in improving knee functional
      status and reducing symptoms: the IKDC score in the PRP group rose from 52.4 +/-
      14.1 to 66.2 +/- 16.7 at 12 months (P < .0005), and in the HA group it rose from
      49.6 +/- 13.0 to 64.2 +/- 18.0 at 12 months (P < .0005). A similar trend was
      observed for all the clinical scores used. The comparative analysis of the 2
      treatments showed no significant intergroup difference at any follow-up
      evaluation in any of the clinical scores adopted. CONCLUSION: PRP does not
      provide a superior clinical improvement with respect to HA, and therefore it
      should not be preferred to viscosupplementation as injective treatment of
      patients affected by knee cartilage degeneration and OA.

PMID- 25952819
TI  - Understanding social development following very preterm birth.

PMID- 25952820
TI  - Collection of normative data for spatial and temporal gait parameters in a sample
      of French children aged between 6 and 12.
AB  - OBJECTIVE: Normative data on gait is essential for clinical practice - especially
      in children whose gait pattern changes over time. Sets of normative gait data in
      healthy children vary significantly from one country to another. We decided to
      generate a specific reference database of gait parameters for French children.
      METHOD: Three hundred and eighty-two children (228 boys and 154 girls, aged
      between 6 and 12) were asked to walk as naturally as possible and at a self
      selected speed on a GAITRite track. Velocity, step count, cadence, step time,
      step length, cycle time, stride length, base width, swing time, stance time,
      single support time and double support time were recorded. Parameters were
      analyzed by age group, height group and BMI. RESULTS: Velocity, step and stride
      length increased regularly with advancing age and height. Cadence decreased with
      height. All temporal parameters (except for double support) differed
      significantly (P<0.05) when comparing the 6-year-old group or the 7-year-old
      group with the 9-year-old group and older groups. A small number of temporal
      parameters (cadence, step time, cycle time and stance time) differed
      significantly when comparing 7-year-olds and 8-year-olds. Temporal parameters
      appeared rise in proportion height from 110 cm to 130 cm and then reached a
      plateau. Overweight was associated with a longer stance time and more double
      support. CONCLUSION: The gait pattern in French children aged between 6 and 12
      differs from those recorded elsewhere in the world; although gait parameters
      appear to change in much the same way with age worldwide, our values (even when
      normalized) are different. Our local database should be of value in French
      studies of childhood gait disorders. Given that gait patterns do not appear to
      mature by the age of 12, it would be valuable to study gait patterns in a
      population of teenagers.

PMID- 25952821
TI  - Is weight gain associated with the incidence of periodontitis? A systematic
      review and meta-analysis.
AB  - AIM: This study aimed to conduct a systematic review assessing the effects of
      weight gain on the incidence of periodontitis in adults. METHODS: Electronic
      searches in four databases were performed up to and including February 2015. Only
      prospective longitudinal studies assessing the association between weight gain
      and the incidence of periodontitis in adults were eligible to be included in this
      study. All studies should state a clear description of nutritional status (Body
      Mass Index; Waist Circumference) as well as the case definition of periodontitis.
      Pooled relative risks (RR) for becoming overweight and obese on the incidence of
      periodontitis were estimated by meta-analysis. Quality was assessed with the
      Newcastle-Ottawa scale for cohort studies. RESULTS: Five articles were included
      in this review and meta-analysis with 42,198 subjects enrolled. Subjects who
      became overweight and obese presented higher risk to develop new cases of
      periodontitis (RR 1.13; 95%CI 1.06-1.20 and RR 1.33 95%CI 1.21-1.47 respectively)
      compared with counterparts who stayed in normal weight. CONCLUSIONS: A clear
      positive association between weight gain and new cases of periodontitis was
      found. However, these results are originated from limited evidence. Thus, more
      studies with longitudinal prospective design are needed.

PMID- 25952822
TI  - Training in trains: an educational program to teach bystander CPR : A LIFE
      PRIORITY Foundation initiative.

PMID- 25952823
TI  - High-dose versus standard dose oseltamivir for treatment of severe influenza in
      adult intensive care unit patients.

PMID- 25952824
TI  - Safety, feasibility, and interest of transthoracic echocardiography in a deployed
      French military Ebola virus disease treatment center in Guinea.

PMID- 25952826
TI  - Probiotic prophylaxis to prevent ventilator-associated pneumonia (VAP) in
      children on mechanical ventilation: an open-label randomized controlled trial-
      response to comments by Saptharishi et al.

PMID- 25952825
TI  - A systematic review and meta-analysis of early goal-directed therapy for septic
      shock: the ARISE, ProCESS and ProMISe Investigators.
AB  - PURPOSE: To determine whether early goal-directed therapy (EGDT) reduces
      mortality compared with other resuscitation strategies for patients presenting to
      the emergency department (ED) with septic shock. METHODS: Using a search strategy
      of PubMed, EmBase and CENTRAL, we selected all relevant randomised clinical
      trials published from January 2000 to January 2015. We translated non-English
      papers and contacted authors as necessary. Our primary analysis generated a
      pooled odds ratio (OR) from a fixed-effect model. Sensitivity analyses explored
      the effect of including non-ED studies, adjusting for study quality, and
      conducting a random-effects model. Secondary outcomes included organ support and
      hospital and ICU length of stay. RESULTS: From 2395 initially eligible abstracts,
      five randomised clinical trials (n = 4735 patients) met all criteria and
      generally scored high for quality except for lack of blinding. There was no
      effect on the primary mortality outcome (EGDT: 23.2% [495/2134] versus control:
      22.4% [582/2601]; pooled OR 1.01 [95% CI 0.88-1.16], P = 0.9, with heterogeneity
      [I(2) = 57%; P = 0.055]). The pooled estimate of 90-day mortality from the three
      recent multicentre studies (n = 4063) also showed no difference [pooled OR 0.99
      (95% CI 0.86-1.15), P = 0.93] with no heterogeneity (I(2) = 0.0%; P = 0.97). EGDT
      increased vasopressor use (OR 1.25 [95% CI 1.10-1.41]; P < 0.001) and ICU
      admission [OR 2.19 (95% CI 1.82-2.65); P < 0.001]. Including six non-ED
      randomised trials increased heterogeneity (I(2) = 71%; P < 0.001) but did not
      change overall results [pooled OR 0.94 (95% CI 0.82 to 1.07); P = 0.33].
      CONCLUSION: EGDT is not superior to usual care for ED patients with septic shock
      but is associated with increased utilisation of ICU resources.

PMID- 25952827
TI  - Expanding the DCD donor pool: prediction of time to death after removal of life
      sustaining treatments.

PMID- 25952828
TI  - An injured brain needs cooling down: no.

PMID- 25952829
TI  - An emotional awakening.

PMID- 25952830
TI  - Misinterpretation of green chemistry.

PMID- 25952831
TI  - Heparan sulfate phage display antibodies recognise epitopes defined by a
      combination of sugar sequence and cation binding.
AB  - Phage display antibodies are widely used to follow heparan sulfate (HS)
      expression in tissues and cells. We demonstrate by ELISA, that cations alter
      phage display antibody binding profiles to HS and this is mediated by changes in
      polysaccharide conformation, demonstrated by circular dichroism spectroscopy.
      Native HS structures, expressed on the cell surfaces of neuroblastoma and
      fibroblast cells, also exhibited altered antibody binding profiles following
      exposure to low mM concentrations of these cations. Phage display antibodies
      recognise conformationally-defined HS epitopes, rather than sequence alone, as
      has been assumed, and resemble proteins in being sensitive to changes in both
      charge distribution and conformation following binding of cations to HS
      polysaccharides. 

PMID- 25952832
TI  - Construction and employment of a low cost laparoscopic simulator. Test on General
      Surgery residents.
AB  - INTRODUCTION: Based on studies that confirm the usefulness of simulators in
      laparoscopic surgical training, we designed and tested a cost-effective solution
      to improve the skills of surgeons training in the operating room. The goal was to
      exercise the basic gestures of laparoscopic surgery. MATERIALS AND METHODS: The
      initial budget of ? 500 was sufficient for this project. We spent only ? 360 on
      the majority of the components, which included buying a laptop. The project was
      performed with material that was readily available online, and the assembly did
      not require special tools. The goal was to make the product easily replicable.
      The test was performed using a simulator on 9 doctors in specialist training in
      general surgery at the University Hospital of Parma distributed, who were equally
      distributed among the six years of school in general surgery. RESULTS: The first
      exercise, which was the simplest, had as its objective the acquisition of
      familiarity with the vision monocular feature of VL and coordination between the
      two hands. We observed statistically significant improvement between the first
      and second (2.52 to 2.17 min, p = 0.006) tests and between the first and third
      (from 2.52 to 1.57 min, p = 0.001) tests with a non-significant correlation
      between the time of year and the achieved specialty. In the second exercise,
      there was a statistically significant improvement due to the excessive excursion
      of the confidence intervals (remarkable variability with overlap of the same
      features). This exercise, which consisted of two parts, explored the ability to
      use two hands independently. The third and final exercise involved the packaging
      of a laparoscopic ligation and was the most complex because it required skill in
      the use of instruments with both hands as well as considerable coordination. The
      t-test for paired data showed a significant improvement in all tests with p =
      0.0008 between the average time for the first and second tests, p = 0.001 between
      the second and third tests, and p = 0.01 between the first and third tests (from
      10.09 min to 3.52 min). CONCLUSIONS: The simulator that we constructed will never
      replace the experience gained in the operating room, and it was not our intention
      to replace the normal process of learning for young surgeons. Instead, we aimed
      to provide an inexpensive tool for refining the basic skills of laparoscopic
      surgery, such as the use of instruments in monocular vision, coordination between
      two hands and ambidexterity.

PMID- 25952833
TI  - Endovascular Treatment for Extracranial Carotid Stenosis: A 10-Year Bibliometric
      Analysis.
AB  - INTRODUCTION: Bibliometric analysis is a quantitative method that can evaluate
      publications related to a specific topic. METHODS: A PubMed database search was
      conducted from 2003 to 2012 using the search term "carotid" AND "stenos*" as a
      part of the title or abstract. RESULTS: A total of 1590 articles were published
      in 329 different journals. A total of 751 (47.2%) publications were original
      articles, 1501 (94.4%) were written in English, 153 (9.6%) received funding, 584
      (36.7%) were published by the United States, and 673 (42.3%) resulted from
      multidisciplinary collaboration. Of the original articles, 538 (71.6%) had
      retrospective design and 275 (36.6%) had sample size of <50. Vascular surgery
      departments produced the most articles (n = 339, 21.3%), followed by radiology (n
      = 270, 17.0%), cardiology (n = 260, 16.4%), neurosurgery (n = 198, 12.5%), and
      neurology (n = 196, 12.3%). Five major departments published only a small portion
      (5.1%-26.5%) of articles in their own specialty journals. CONCLUSION: The
      publication in journals across disciplines and multidisciplinary collaboration
      are 2 peculiar characteristics of research in this topic.

PMID- 25952834
TI  - Use of polyaspartate as inhibitor of tartaric precipitations in wines.
AB  - All additives used to stabilize wines against the precipitations of potassium
      bitartrate have some limits: metatartaric acid (MTA) is effective but very
      unstable, carboxymethylcellulose is stable and effective in white wines but
      affects color stability in red wines, mannoproteins have a variable effectiveness
      depending on wine composition. This work was aimed at testing the effect of new
      stabilizing products on tartaric precipitations, focusing on the use of Na and K
      polyaspartate salts (PASPs). The effectiveness of 4 different PASPs and 1 MTA
      added to red and white wines was compared using the mini-contact test and cold
      test. The dose effect and the stability of the products over time were also
      studied. The PASPs showed a similar stabilizing effect and a longer stability
      over time compared to MTA. PASPs can be considered interesting as additives for
      wine tartaric stabilization. Further work is in progress to better characterize
      their enological properties. 

PMID- 25952835
TI  - Determination of veterinary antibiotics in bovine urine by liquid chromatography
      tandem mass spectrometry.
AB  - A follow-up of antibiotics (tetracyclines, fluoroquinolones, cephalosporins,
      penicillins and amphenicols) in the bovine urine is important for two reasons: to
      understand if they are still present in organism, and whether their occurrence in
      urine might be considered as an environmental risk. A validated HPLC-MS/MS method
      (Decision 2002/657/EC) for antibiotics determination in bovine urine was
      developed. CCalpha and CCbeta were in the range of 0.58-0.83 and 0.55-1.1 ng mL(
      1), respectively. Recoveries were 92-108%, with inter-day repeatability below
      12%. Analysis of bovine urine revealed frequent presence of tetracyclines, which
      was related with animal's age. The cause, most presumably, might be found in
      different therapeutic protocols applied for veal calves and young bulls enrolled
      in this study. Most abundant was oxytetracycline with highest level in veal
      calves (1718 ng mL(-1)) vs. young bulls (2.8 ng mL(-1)). Our results indicate the
      necessity of antibiotics monitoring in bovine urine before animals undergo
      further processing in the food industry.

PMID- 25952836
TI  - Scientific validation of synergistic antioxidant effects in commercialised
      mixtures of Cymbopogon citratus and Pterospartum tridentatum or Gomphrena globosa
      for infusions preparation.
AB  - Pterospartum tridentatum (L.) Willk., Gomphrena globosa L. and Cymbopogon
      citratus (DC) Stapf. are examples of medicinal plants with antioxidant properties
      on their own, but that can be improved when mixed. In the present work, the
      antioxidant activity and phenolic compounds were determined in the infusions
      prepared from the individual plants, and from mixtures of these plants in
      different proportions. P. tridentatum > C. citratus > G. globosa was the order
      observed for antioxidant efficacy, which can be related to their different
      composition in phenolic compounds. Synergism was the main effect observed among
      the tested mixtures, mainly for the infusions prepared from the plants in
      proportion 40%:60% (either P. tridentatum and C. citratus; or G. globosa and C.
      citratus). The infusion obtained with 40% of P. tridentatum and 60% of C.
      citratus gave the highest antioxidant properties. The present study validates the
      commercialisation of the studied plants combined in specific proportions.

PMID- 25952837
TI  - Characterisation of free and bound volatile compounds from six different
      varieties of citrus fruits.
AB  - Free volatile compounds in six varieties of citrus juices were analyzed by solid
      phase microextraction-gas chromatography-mass spectrometry. Bound fractions were
      isolated and extracted with methanol and Amberlite XAD-2 resin and then
      hydrolyzed by almond beta-glucosidase. A total of 43 free and 17 bound volatile
      compounds were identified in citrus. Free volatile contents in sweet orange were
      the most abundant, followed by those in grapefruits and mandarins. Among free
      volatiles, terpenes were the most abundant in citrus juice. Sensory analysis
      results showed that the flavor of the same citrus cultivars was similar, but the
      flavor of different cultivars varied. Among bound volatiles, benzenic compounds
      were the most abundant in these citrus juices. Bound volatiles also significantly
      differed among cultivars. In addition, only p-vinylguaiacol were detected in all
      of the samples. 

PMID- 25952838
TI  - Coencapsulation of Ferulic and Gallic acid in hp-b-cyclodextrin.
AB  - The complexes formed by two polyphenols, trans-Ferulic acid (FA) and Gallic acid
      (GA) with 2-hydroxypropyl-b-cyclodextrin (HPbetaCD), by the spray-drying method,
      were studied. Encapsulation-efficiencies (EE) of the complexes prepared were
      evaluated by HPLC. In the case of co-encapsulation, the EE of GA was lowered,
      whereas that of FA was almost stable, indicating a possible antagonistic
      relationship between the two phenols for the HPbetaCD cavity. The physicochemical
      characterization of the complexes was carried out by Fourier Transform Infrared
      Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), and Scanning
      Electron Microscopy (SEM). SEM observations revealed that the coencapsulated
      phenolic complex resulted in a more rounded shape outer surfaces of HPbetaCD than
      when encapsulated separately. FT-IR and DSC data indicated that the two
      polyphenols exhibit a possible interaction in the coencapsulated complex. The
      complexes showed no loss of their ability to scavenge DPPH radical relatively to
      the single agent at the concentrations used. 

PMID- 25952839
TI  - Comparison of phenolic profiles and antioxidant properties of European Fagopyrum
      esculentum cultivars.
AB  - The purpose of this study was to investigate composition and content of phenolic
      compounds in seeds of common buckwheat (Fagopyrum esculentum Moench) cultivars
      from Western, Central and Southeastern Europe grown in the Balkan area, and to
      compare them with cultivars from the Balkan. Mostly detected hydroxycinnamic
      acids in seeds of the investigated cultivars were caffeic and chlorogenic acid
      derivatives. More than ten different flavanols were detected in the investigated
      seeds, based on which all tested buckwheat cultivars were divided into two
      groups: those with high propelargonidins (epiafzelechin-epicatechin) and those
      with high procyanidins contents. 'Novosadska' had the highest level of phenolic
      acids, proanthocyanidins, flavones and most of the flavonols. However, 'Bosna 1'
      and 'Bosna 2' were highlighted with the greatest rutin content (up to 46 times
      higher than in other cultivars). All buckwheat cultivars had quite high
      antioxidant capacity (more than 80% of neutralized radicals), yet, 'Novosadska',
      'Godijevo', 'Spacinska 1' and 'Bamby' excelled. 

PMID- 25952840
TI  - Impact of quercetin and fish oil encapsulation on bilayer membrane and oxidation
      stability of liposomes.
AB  - Unsaturated soy phosphatidyl choline (PC) liposomes were systematically analyzed
      for chemical and physical stability and for influence on membrane fluidity, when
      quercetin and fish oil were encapsulated. The physical stability of liposomes was
      lowered with loading, which is mainly due to fish oil leakage. While fish oil did
      not induce oxidative acceleration, quercetin did not reduce lipid-derived radical
      formation but it did inhibit hexanal formation. It also showed no relevant
      effects on membrane fluidity, polarity or partitioning of the spin probe TEMPOL
      benzoate (TB), as proved by EPR measurements and simulation. However, increasing
      concentration of fish oil in a membrane might increase the acyl chain dynamics
      and therefore apply a more attractive environment for TB. In contrast to the
      encapsulates increasing fluidity of saturated membranes by disturbing the lipid
      packing, membrane properties of unsaturated systems with a Tm below 0  degrees C
      were not influenced by encapsulation of quercetin or fish oil.

PMID- 25952841
TI  - Pilot-scale subcritical solvent extraction of curcuminoids from Curcuma long L.
AB  - Curcuminoids consisted curcumin, demethoxycurcumin and bisdemethoxycurcumin, were
      extracted from turmeric using subcritical solvent by varying conditions of
      temperature (110-150  degrees C), time (1-10 min), pressure (5-100 atm), solid-to
      solvent ratio, and mixing ratio of solvent. Preliminary lab-scale experiments
      were conducted to determine the optimum extraction temperature and mixing ratio
      of water and ethanol for the pilot-scale extraction. The maximum yield of
      curcuminoids in the pilot-scale system was 13.58% (curcumin 4.94%,
      demethoxycurcumin 4.73%, and bisdemethoxycurcumin 3.91% in dried extracts) at 135
      degrees C/5 min with water/ethanol mixture (50:50, v/v) as a solvent. On the
      other hand, the extraction yields of curcuminoids were obtained as 10.49%, 13.71%
      and 13.96% using the 50%, 95% and 100% ethanol, respectively, at the atmospheric
      condition (60  degrees C/120 min). Overall results showed that the subcritical
      solvent extraction is much faster and efficient extraction method considering
      extracted curcuminoids contents and has a potential to develop a commercial
      process for the extraction of curcuminoids.

PMID- 25952844
TI  - Exploitation of the complexation reaction of ortho-dihydroxylated anthocyanins
      with aluminum(III) for their quantitative spectrophotometric determination in
      edible sources.
AB  - Anthocyanins are natural pigments known for their color and antioxidant activity.
      These properties allow their use in various fields, including food and
      pharmaceutical ones. Quantitative determination of anthocyanins had been
      performed by non-specific methods that limit the accuracy and reliability of the
      results. Therefore, a novel, simple spectrophotometric method for the
      anthocyanins quantification based on a formation of blue-colored complexes by the
      known reaction between catechol- and pyrogallol-containing anthocyanins and
      aluminum(III) is presented. The method demonstrated to be reproducible,
      repetitive (RSD<1.5%) and highly sensitive to ortho-dihydroxylated anthocyanins
      (LOD = 0.186 MUg/mL). Compliance with Beer's law was also evident in a range of
      concentrations (2-16 MUg/mL for cyanidin 3-O-glucoside). Good recoveries (98.8
      103.3%) were calculated using anthocyanin-rich plant samples. The described
      method revealed direct correlation to pH differential method results for several
      common anthocyanin-containing fruits indicating its great analytical potential.
      The presented method was successfully validated.

PMID- 25952843
TI  - Optimisation of stir-bar sorptive extraction (SBSE), targeting medium and long
      chain free fatty acids in cooked ham exudates.
AB  - The purpose of our research was to optimise the extraction conditions of the stir
      bar sorptive extraction (SBSE) targeting the identification of lipid compounds
      particularly medium and long-chain free fatty acids in cooked cured pork ham
      exudates. The analytical conditions of extraction (including sample volume,
      extraction time, stirring speed, pH and dilution of the sample) were checked
      using the Simplex method approach. As a result of the SBSE optimisation, improved
      detection limits and linear ranges for hexanoic, heptanoic, octanoic, nonanoic,
      decanoic, dodecanoic and tetradecanoic fatty acids were obtained. When comparing
      results with those obtained by the commonly used SPME methodology, optimisation
      of SBSE achieved better results for volatile compounds of low volatility, such as
      medium and long-chain free fatty acids, whereas compounds with high volatility
      and polarity were only detected by SPME. SBSE also confirmed its potential as a
      tool to help identify undesirable contaminants/residues in meat products. 

PMID- 25952842
TI  - Breads enriched with guava flour as a tool for studying the incorporation of
      phenolic compounds in bread melanoidins.
AB  - In the present study we aimed at studying, for the first time, the incorporation
      of phenolic compounds into bread melanoidins. Fermentation significantly affected
      the phenolics profile of bread doughs. Melanoidins contents continuously
      increased from 24.1 mg/g to 71.9 mg/g during baking, but their molecular weight
      decreased at the beginning of the process and increased thereafter. Enrichment of
      white wheat bread with guava flour increased the incorporation of phenolic
      compounds up to 2.4-fold. Most phenolic compounds showed higher incorporation
      than release rates during baking, leading to increases from 3.3- to 13.3-fold in
      total melanoidin-bound phenolics. Incorporation patterns suggested that phenolic
      hydroxyls, but not glycosidic bonds of melanoidin-bound phenolics are cleaved
      during thermal processing. Antioxidant capacity of bread melanoidins increased
      due to enrichment with guava flour and increasing baking periods and was
      partially attributed to bound phenolics. Moreover, FRAP assay was more sensitive
      to measure this parameter than TEAC assay.

PMID- 25952845
TI  - Preparation and physicochemical properties of soluble dietary fiber from orange
      peel assisted by steam explosion and dilute acid soaking.
AB  - The coupled pretreatment of orange peel with steam explosion (SE) and sulfuric
      acid soaking (SAS) was investigated to enhance the yield and improve the
      functionality of soluble dietary fiber (SDF). When orange peel was pretreated by
      SE at 0.8MPa for 7 min, combined with 0.8% SAS, the content of SDF was increased
      from 8.04% to 33.74% in comparison to the control and SDF prepared with SE-SAS
      showed the high water solubility, water-holding capacity, oil-holding capacity,
      swelling capacity, emulsifying activity, emulsion stability and foam stability.
      SDF from orange peel treated by SE-SAS exhibited significantly (p < 0.05) higher
      binding capacity for three toxic cations (Pb, As and Cu) and smaller molecular
      weight (Mw = 174 kDa). Furthermore, differential scanning calorimetry (DSC)
      measurement showed that SDF from orange peel treated by SE-SAS had a higher peak
      temperature (170.7 +/- 0.4  degrees C) than that of the untreated sample (163.4
      +/- 0.3  degrees C). Scanning electron micrograph (SEM) images demonstrated that
      the surface of SDF from orange peel treated by SE-SAS was rough and collapsed. It
      can be concluded that SDF from orange peel treated by SE-SAS has the higher
      potential to be applied as a functional ingredient in food products.

PMID- 25952846
TI  - Effects of sprouting and postharvest storage under cool temperature conditions on
      starch content and antioxidant capacity of green pea, lentil and young mung bean
      sprouts.
AB  - The effects of germination of selected legumes and further storage of sprouts
      under cool conditions on the phenolics, antioxidant activity and starch content
      and their potential bioaccessibility were elucidated. In green pea and mung bean
      sprouts a slight increase of chemically extractable phenolics (including
      flavonoids) during the first 4 days of sprouting was observed. Digestion in vitro
      released phenolics; however, flavonoids were poorly bioaccessible. Storage of
      green pea sprouts decreased reducing power and increased the antiradical ability.
      Reducing potential of potentially bioaccessible fraction of stored lentil sprouts
      was elevated of 40%, 31% and 23% in 3-, 4- and 5-day-old sprouts, respectively.
      Postharvest storage significantly increases the starch digestibility and values
      of expected glycemic index (eGI)--the highest eGIs were determined for 5-day-old
      stored sprouts; 75.17-green pea, 83.18-lentil and 89.87-mung bean. Bioactivity
      and nutritional quality of legumes is affected by sprouting and further storage
      at low temperatures.

PMID- 25952847
TI  - Optimization of hydrolysis conditions for bovine plasma protein using response
      surface methodology.
AB  - The purpose of this study was to establish optimal conditions for the hydrolysis
      of bovine plasma protein. Response surface methodology was used to model and
      optimize responses [degree of hydrolysis (DH), 2,2-diphenyl-1-picrydrazyl (DPPH)
      radical-scavenging activity and Fe(2+)-chelating activity]. Hydrolysis
      conditions, such as hydrolysis temperature (46.6-63.4  degrees C), hydrolysis
      time (98-502 min), and hydrolysis pH (6.32-9.68) were selected as the main
      processing conditions in the hydrolysis of bovine plasma protein. Optimal
      conditions for maximum DH (%), DPPH radical-scavenging activity (%) and Fe(2+)
      chelating activity (%) of the hydrolyzed bovine plasma protein, were respectively
      established. We discovered the following three conditions for optimal hydrolysis
      of bovine plasma: pH of 7.82-8.32, temperature of 54.1  degrees C, and time of
      338.4-398.4 min. We consequently succeeded in hydrolyzing bovine plasma protein
      under these conditions and confirmed the various desirable properties of optimal
      hydrolysis.

PMID- 25952848
TI  - The antibiotic activity and mechanisms of sugarcane (Saccharum officinarum L.)
      bagasse extract against food-borne pathogens.
AB  - Sugarcane bagasse contains natural compositions that can significantly inhibit
      food-borne pathogens growth. In the present study, the phenolic content in
      sugarcane bagasse was detected as higher than 4 mg/g dry bagasse, with 470 mg
      quercetin/g polyphenol. The sugarcane bagasse extract showed bacteriostatic
      activity against the growth of Staphylococcus aureus, Listeria monocytogenes,
      Escherichia coli and Salomonella typhimurium. Additionally, the sugarcane bagasse
      extract can increase the electric conductivity of bacterial cell suspensions
      causing cellular leaking of electrolytes. Results of sodium dodecyl sulfate
      polyacrylamide gel electrophoresis suggested the antibacterial mechanism was
      probably due to the damaged cellular proteins by sugarcane bagasse extract. The
      results of scanning electron microscopy and transmission electron microscopy
      showed that the sugarcane bagasse extract might change cell morphology and
      internal structure.

PMID- 25952849
TI  - Investigating chemical changes during shelf-life of thermal and high-pressure
      high-temperature sterilised carrot purees: A 'fingerprinting kinetics' approach.
AB  - This work investigates chemical changes during shelf-life of thermally and high
      pressure high temperature (HPHT) sterilised carrot purees using a 'fingerprinting
      kinetics' approach. Fingerprinting enabled selection of Strecker aldehydes,
      terpenes, phenylpropanoids, fatty acid derivatives and carotenoid degradation
      products as volatiles clearly changing during shelf-life. Next, kinetic modelling
      of these volatiles was performed to compare their reaction kinetics during
      storage in differently sterilised samples. Immediately after processing, the
      Strecker aldehydes were detected at higher levels in thermally sterilised
      samples. During storage, the compounds increased at a comparable rate in
      thermally and HPHT processed samples. In contrast, immediately after processing,
      most of the naturally occurring terpenes and phenylpropanoids were better
      preserved in HPHT treated samples. Nevertheless, by the end of storage, the
      concentration of these compounds decreased to almost the same level in both
      thermal and HPHT samples (with a higher degradation rate in HPHT samples). 

PMID- 25952850
TI  - Melatonin treatment of pre-veraison grape berries to increase size and
      synchronicity of berries and modify wine aroma components.
AB  - A comprehensive investigation was carried out to determine the effect of
      exogenous melatonin treatment of pre-veraison grapes on grape berries and its
      wines. Two melatonin treatments of pre-veraison grape berries increased the
      weight of the berries by approximately 6.6%. Meanwhile, this melatonin treatment
      could be beneficial in the reduction of underripe and overripe fruits and in
      enhancing the synchronicity of the berries. In addition, there were significant
      differences in the volatile compound composition between the wine produced from
      the melatonin-treated berries and the wines made from untreated berries. The wine
      from melatonin-treated pre-veraison grape berries had stronger fruity, spicy, and
      sweet sensory properties, compared to the wines made from untreated berries.
      Prolonging the treatment through repeated applications can enhance these effects
      and under different seasonal conditions, more pronounced effects on the grape
      quality and wine properties can be observed. 

PMID- 25952851
TI  - Chlorogenic acid-arabinose hybrid domains in coffee melanoidins: Evidences from a
      model system.
AB  - Arabinose from arabinogalactan side chains was hypothesized as a possible binding
      site for chlorogenic acids in coffee melanoidins. To investigate this hypothesis,
      a mixture of 5-O-caffeoylquinic acid (5-CQA), the most abundant chlorogenic acid
      in green coffee beans, and (alpha1 -> 5)-L-arabinotriose, structurally related to
      arabinogalactan side chains, was submitted to dry thermal treatments. The
      compounds formed during thermal processing were identified by electrospray
      ionization mass spectrometry (ESI-MS) and characterized by tandem MS (ESI-MS(n)).
      Compounds composed by one or two CQAs covalently linked with pentose (Pent)
      residues (1-12) were identified, along with compounds bearing a sugar moiety but
      composed exclusively by the quinic or caffeic acid moiety of CQAs. The presence
      of isomers was demonstrated by liquid chromatography online coupled to ESI-MS and
      ESI-MS(n). Pent1-2CQA were identified in coffee samples. These results give
      evidence for a diversity of chlorogenic acid-arabinose hybrids formed during
      roasting, opening new perspectives for their identification in melanoidin
      structures.

PMID- 25952852
TI  - Multivariate optimization of ultrasound-assisted extraction for determination of
      Cu, Fe, Ni and Zn in vegetable oils by high-resolution continuum source atomic
      absorption spectrometry.
AB  - An assisted liquid-liquid extraction of copper, iron, nickel and zinc from
      vegetable oil samples with subsequent determination by high-resolution continuum
      source flame atomic absorption spectrometry (HR-CS FAAS) was optimized by
      applying a full factorial design in two levels and the response surface
      methodology, Box-Behnken. The effects of the acid concentration and the
      amplitude, cycle and time of sonication on the extraction of the analytes, as
      well as their interactions, were assessed. In the selected condition (sonication
      amplitude = 66%, sonication time = 79 s, sonication cycle = 74%), using 0.5 mol
      L(-1) HCl as the extractant, the limits of quantification were 0.14, 0.20, 0.21
      and 0.04 MUg g(-1) for Cu, Fe, Ni and Zn, respectively, with R.S.D. ranging from
      1.4% to 3.6%. The proposed method was applied for the determination of the
      analytes in soybean, canola and sunflower oils.

PMID- 25952853
TI  - Compactible powders of omega-3 and beta-cyclodextrin.
AB  - Omega-3 fatty acids are used in both nutraceuticals and pharmaceuticals in the
      form of triglycerides and ethyl esters. Administration forms available for omega
      3 include bulk oil, soft gel capsules, emulsions and some powder compositions.
      Cyclodextrins are substances well known for their ability to encapsulate
      lipophilic molecules. In the present work, powders loaded with omega-3 oil,
      ranging from 10 to 40% (w/w), have been prepared by vacuum drying, freeze drying
      or spray granulation of aqueous mixtures of omega-3 oil and beta-cyclodextrin.
      The powders were found to be partially crystalline by powder X-ray diffraction
      and to contain crystalline phases not present in pure beta-cyclodextrin,
      indicating true complexation. The compactibility of the powders has been
      explored, revealing that a dry and compactible powder can be prepared from
      various omega-3 oils and beta-cyclodextrin. Spray granulation was found to be the
      superior drying method for the preparation of compactible powders. 

PMID- 25952854
TI  - Identification and antioxidant properties of polyphenols in lotus seed epicarp at
      different ripening stages.
AB  - In this study, polyphenols from lotus seed epicarp (PLSE) at three different
      ripening stages were purified by column chromatography and identified by RP-HPLC
      and HPLC-ESI-MS(2). The antioxidant activities of PLSE were also investigated. We
      found that the contents of PLSE at the green ripening stage, half ripening stage
      and full ripening stage are 13.08%, 10.95% and 6.73% respectively. The levels of
      catechin, epicatechin, hyperoside, and isoquercitrin in PLSE at the three
      different ripening stages were different. Moreover, the amounts of catechin and
      epicatechin decreased, while the contents of hyperoside and isoquercitrin
      increased as the seed ripened. We found that PLSE at three different ripening
      stages had good scavenging abilities on DPPH and ABTS(+) radicals. However, the
      scavenging ability decreased with maturation. Our results may be valuable with
      regard to the utilization of lotus seed epicarp as a functional food material. 

PMID- 25952855
TI  - Fish species substitution and misnaming in South Africa: An economic, safety and
      sustainability conundrum revisited.
AB  - While fish species mislabelling has emerged as a global problem, the tracking of
      improvements or deteriorations in seafood trading practices is challenging
      without a consistent basis for monitoring. The aim of this study was to develop a
      robust, repeatable species authentication protocol that could be used to
      benchmark the current and future incidences of fish mislabelling in South Africa.
      Using this approach, 149 fish samples collected from restaurants and retailers in
      three provinces (KwaZulu-Natal, Western Cape and Gauteng) were identified using
      DNA barcoding, supplemented in certain cases with mitochondrial control region
      sequencing. Overall, 18% of samples were incorrectly described in terms of
      species, with similar misrepresentation rates in restaurants (18%) and retail
      outlets (19%). While there appears to be some improvement in the transparency of
      local seafood marketing compared to previous studies, the results remain of
      concern and signal the need for enhanced seafood labelling regulations,
      monitoring and law enforcement. 

PMID- 25952856
TI  - Coffee fermentation and flavor--An intricate and delicate relationship.
AB  - The relationship between coffee fermentation and coffee aroma is intricate and
      delicate at which the coffee aroma profile is easily impacted by the fermentation
      process during coffee processing. However, as the fermentation process in coffee
      processing is conducted mainly for mucilage removal, its impacts on coffee aroma
      profile are usually neglected. Therefore, this review serves to summarize the
      available literature on the impacts of fermentation in coffee processing on
      coffee aroma as well as other unconventional avenues where fermentation is
      employed for coffee aroma modulation. Studies have noted that proper control over
      the fermentation process imparts desirable attributes and prevents undesirable
      fermentation which generates off-flavors. Other unconventional avenues in which
      fermentation is employed for aroma modulation include digestive bioprocessing and
      the fermentation of coffee extracts and green coffee beans. The latter is an area
      that should be explored further with appropriate microorganisms given its
      potential for coffee aroma modulation. 

PMID- 25952857
TI  - Synthesis and antibacterial properties of 2,3-dideoxyglucosides of terpene
      alcohols and phenols.
AB  - Essential oils and their oxygenated terpene constituents possess potent
      antimicrobial properties. In the present study, a facile synthetic route to the
      2,3-dideoxy 1-O-glucosides of important phenols and terpene alcohols in excellent
      yields (85-96%) has been delineated. Studies on their antimicrobial action
      against four food-borne pathogens--Bacillus cereus, Staphylococcus aureus,
      Escherichia coli and Yersinia enterocolitica--demonstrated that the zone of
      inhibition, in general, was higher for the 2,3-unsaturated 1-O-glucoside
      derivatives (1b-6b) and the corresponding saturated glucosides (1c-5c) when
      compared to the parent alcohols/phenols (1-6). The minimum inhibitory
      concentration (MIC) and minimum bactericidal concentration (MBC) values for these
      derivatives too were generally lower than those of the parent compounds.
      Furthermore, the time-kill and bacteriolysis assays too demonstrated the greater
      antimicrobial potential of the derivatives. The 2,3-dideoxy 1-O-glucosides of
      phenols and terpene alcohols were more effective in their antimicrobial action
      than the corresponding parent compounds. The study indicated that these novel
      derivatives can find useful application in control of food-related pathogenic
      microbes in foods.

PMID- 25952858
TI  - The chemistry of sour taste and the strategy to reduce the sour taste of beer.
AB  - The contributions of free hydrogen ions, undissociated hydrogen ions in
      protonated acid species, and anionic acid species to sour taste were studied
      through sensory experiments. According to tasting results, it can be inferred
      that the basic substance producing a sour taste is the hydrogen ion, including
      free hydrogen ions and undissociated hydrogen ions. The intensity of a sour taste
      is determined by the total concentration of free hydrogen ions and undissociated
      hydrogen ions. The anionic acid species (without hydrogen ions) does not produce
      a sour taste but can intensify or weaken the intensity of a sour taste. It seems
      that hydroxyl or conjugated groups in anionic acid species can intensify the sour
      taste produced by hydrogen ions. The following strategy to reduce the sensory
      sourness is advanced: not only reduce free hydrogen ions, namely elevate pH
      value, but also reduce the undissociated hydrogen ions contained in protonated
      acid species. 

PMID- 25952859
TI  - Changes occurring in compositions and antioxidant properties of healthy soybean
      seeds [Glycine max (L.) Merr.] and soybean seeds diseased by Phomopsis longicolla
      and Cercospora kikuchii fungal pathogens.
AB  - Changes in the compositions (isoflavone, protein, oil, and fatty acid) and
      antioxidant properties were evaluated in healthy soybeans and soybeans diseased
      by Phomopsis longicolla and Cercospora kikuchii. The total isoflavone content
      (1491.3 MUg/g) of healthy seeds was observed to be considerably different than
      that of diseased seeds (P. longicolla: 292.6, C. kikuchii: 727.2 MUg/g), with
      malonlygenistin exhibiting the greatest decrease (726.1 -> 57.1, 351.9 MUg/g).
      Significantly, three isoflavones exhibited a slight increase, and their
      structures were confirmed as daidzein, glycitein, and genistein, based on their
      molecular ions at m/z 253.1, 283.0, and 269.1 using the negative mode of HPLC-DAD
      ESI/MS. The remaining compositions showed slight variations. The effects against
      2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzthiazoline-6
      sulphonic acid) radicals in healthy seeds were stronger than the diseased
      soybeans, depending upon the isoflavone level. Our results may be useful in
      evaluating the relationship between composition and antioxidant activity as a
      result of changes caused by soybean fungal pathogens.

PMID- 25952860
TI  - Effect of CaCl2 on denaturation and aggregation of silver carp myosin during
      setting.
AB  - The effect of CaCl2 on denaturation and aggregation of silver carp myosin
      incubated at 40  degrees C was investigated by circular dichroism spectroscopy,
      surface hydrophobicity (S0-ANS), total sulfhydryl (SH) group content, zeta
      potential, turbidity, z-average diameter (dz), and dynamic rheological analysis.
      During setting at 40  degrees C, both CaCl2 and heating induced conformational
      changes of the fish myosin, and exposure of more hydrophobic amino acid residues
      and free SH groups, followed by myosin aggregation via hydrophobic interactions
      and disulfide bonds. Additionally, turbidity and dz of myosin increased
      significantly with increasing CaCl2 concentration, and the added CaCl2 further
      increased the extent and rate of aggregation of myosin by promoting the formation
      of Ca bridges. Myosin with 60 mM CaCl2 showed the maximal G' value and the
      highest rate of G' development. However, the G' value would decrease with an
      excessive amount of CaCl2 (100 mM).

PMID- 25952861
TI  - Calorimetry, chemical composition and in vitro digestibility of oilseeds.
AB  - The objective of the study was to determine the quality of sunflower, soybean,
      crambe, radish forage and physic nut, by measuring chemical composition, in vitro
      digestibility and kinetics of thermal decomposition processes of mass loss and
      heat flow. Lipid was inversely correlated with protein of whole seed (R = -0.67),
      meal (R = -0.95), and press cake (R = -0.78), and positively correlated with the
      enthalpy (DeltaH) of whole seed. Soybean seed and meal presented a high in vitro
      digestibility but poor energy sources with DeltaH averaging 5907.5 J/g and
      2570.1J/g for whole seed and meal, respectively. As suggested by the release of
      heat, measured by DeltaH, whole seeds of crambe (6295.1J/g), radish forage
      (6182.7 J/g), and physic nut (6420.0 J/g) may be potential energy sources for
      ruminant animals. The thermal analysis provided additional information besides
      that obtained from the usual wet chemistry and in vitro measurements.

PMID- 25952862
TI  - Effects of canola proteins and hydrolysates on adipogenic differentiation of
      C3H10T/2 mesenchymal stem cells.
AB  - This study assessed the ability of canola protein isolate (CPI) and enzymatic
      hydrolysates (CPHs) to inhibit adipogenic differentiation of C3H10T1/2 murine
      mesenchymal stem cells in vitro. Cell viability was maintained at concentrations
      of 60 MUg/ml of sample. Cells treated with Alcalase hydrolysate demonstrated a
      higher reduction in anti-adipogenic differentiation through quantitation by oil
      red O staining. qPCR analysis showed that CPI and CPH-treated cells significantly
      inhibited PPARgamma expression, a key transcription factor involved in adipocyte
      differentiation, as evident in an ~ 60-80% fold reduction of PPARgamma mRNA.
      Immunofluorescence staining for PPARgamma protein also showed a reduced
      expression in some treated cells when compared to differentiated untreated cells.
      The 50% inhibition concentration (IC50) of CPI, CPHs and their membrane
      ultrafiltration fractions on pancreatic lipase (PL) activity ranged between 0.75
      and 2.5 mg/ml, (p < 0.05) for the hydrolysed and unhydrolysed samples. These
      findings demonstrate that CPI and CPHs contain bioactive components which can
      modulate in vitro adipocyte differentiation.

PMID- 25952863
TI  - Detection of bisphenol A in food packaging based on fluorescent conjugated
      polymer PPESO3 and enzyme system.
AB  - Bisphenol A (BPA) is a kind of carcinogen, which can interfere with the body's
      endocrine system. In this paper, a new kind of fluorescent sensor for BPA
      detection was established based on the fluorescent conjugated polymer PPESO3. The
      oxidative product of BPA is able to quench PPESO3 in the presence of HRP and
      H2O2, and the quenched PL intensity of PPESO3 was proportionally to the
      concentration of BPA in the range of 1-100 MUmol/L with a detection limit of 4 *
      10(-7) mol/L. The proposed method has been applied to detect BPA in eight food
      packaging samples with satisfactory results. The proposed method has the
      potential for the assay of BPA in food or food packaging samples.

PMID- 25952864
TI  - Determination of free and bound phenolic compounds in soy isoflavone concentrate
      using a PFP fused core column.
AB  - In the last years, the consumption of soy-based foods has increased due to the
      health benefits related to soy bioactives like phenolic compounds. Thus, in the
      present study, a new chromatographic method using reverse-phase high performance
      liquid chromatography coupled to diode array detection (RP-HPLC/DAD) was
      developed using a fused core pentafluorophenyl (PFP) column. The established
      method allowed the determination of twenty-one free phenolic compounds and eleven
      bound phenolics in a soy isoflavone concentrate. The method was validated in
      terms of precision and recovery. Intra and inter-day precision were less than 5%
      (% RSD) and the recovery was between 97.4% and 103.6%. Limits of quantification
      (LOQs) ranged between 0.093 and 0.443 MUg/mL. Because of that, PFP stationary
      phase can be easily applied for routine determination of phenolic compounds in
      soy based foods.

PMID- 25952865
TI  - Development of hyperspectral imaging coupled with chemometric analysis to monitor
      K value for evaluation of chemical spoilage in fish fillets.
AB  - K value is an important freshness index widely used for indication of nucleotide
      degradation and assessment of chemical spoilage. The feasibility of hyperspectral
      imaging (400-1000 nm) for determination of K value in grass carp and silver carp
      fillets was investigated. Partial least square (PLS) regression and least square
      support vector machines (LS-SVM) models established using full wavelengths showed
      excellent performances and the PLS model was better with higher determination
      coefficients of prediction (R(2)P = 0.936) and lower root mean square errors of
      prediction (RMSEP = 5.21%). The simplified PLS and LS-SVM models using the seven
      optimal wavelengths selected by successive projections algorithm (SPA) also
      presented good performances. The spatial distribution map of K value was
      generated by transferring the SPA-PLS model to each pixel of the images. The
      current study showed the suitability of using hyperspectral imaging to determine
      K value for evaluation of chemical spoilage and freshness of fish fillets.

PMID- 25952866
TI  - Thermal reversibility of vitamin E-enriched emulsion-based delivery systems
      produced using spontaneous emulsification.
AB  - The influence of temperature scanning and isothermal storage conditions on
      turbidity, particle size, and thermal reversibility of vitamin E-enriched
      emulsions produced by spontaneous emulsification was examined. Initially, the
      mini-emulsions formed were optically transparent and contained small droplets (d
      ~ 44 nm). When heated (20-90  degrees C), emulsions exhibited a complex turbidity
      temperature profile with a phase inversion temperature (PIT) at ~ 75-80  degrees
      C. Temperature scanning rate had a major influence on emulsion thermal
      reversibility. Slow heating (0.5  degrees C/min) above the PIT followed by quench
      cooling (~ 67  degrees C min(-1)) to 30  degrees C did not appreciably increase
      turbidity or droplet diameter (d ~ 50 nm), suggesting these systems were thermo
      reversible. However, slow heating to temperatures below the PIT followed by rapid
      cooling appreciably increased droplet size and turbidity (thermo-irreversible).
      Cooling rate also affected emulsion thermo-reversibility: the turbidity and
      droplet size after heating above the PIT decreased with increasing cooling rate.

PMID- 25952867
TI  - Fluorescence quenching study of resveratrol binding to zein and gliadin: Towards
      a more rational approach to resveratrol encapsulation using water-insoluble
      proteins.
AB  - Several health benefits have been ascribed to consumption of resveratrol, a
      polyphenol that can be extracted from grape skins. However, its use as a
      nutraceutical ingredient is compromised by its low water solubility, chemical
      stability, and bioavailability. Encapsulation of resveratrol in protein
      nanoparticles can be used to overcome these issues. Fluorescence quenching
      experiments were used to study the interaction of resveratrol with gliadin and
      zein. Resveratrol interacted with both proteins, but the binding constant was
      higher for zein than for gliadin at 35  degrees C. Furthermore, binding between
      resveratrol and gliadin increased at higher temperatures, which was not observed
      for zein. Analysis of the thermodynamic parameters suggested that resveratrol
      gliadin binding mainly occurs through hydrophobic interactions while the binding
      with zein is predominantly mediated through hydrogen bonds. These results help
      rationalise ingredient selection and production of protein nanoparticles and
      microparticles for encapsulation, protection and release of resveratrol and
      potentially other bioactive compounds.

PMID- 25952868
TI  - Fatty acids, mercury, and methylmercury bioaccessibility in salmon (Salmo salar)
      using an in vitro model: Effect of culinary treatment.
AB  - The effect of culinary treatments on the fatty acid profile, mercury (Hg), and
      methylmercury (MeHg) levels of salmon was studied. The bioaccessibility of fatty
      acids, Hg, and MeHg in raw and grilled salmon was determined. The most intense
      thermal treatment (grilling) did not alter the relative fatty acid (FA) profile.
      There were bioaccessibility differences between FAs. To the authors' knowledge,
      for the first time, higher bioaccessibility of the long-chain FAs than the short-
      and medium-chain FAs was measured. Chemical interaction phenomena seemed to play
      a role. On the other hand, higher levels of unsaturation decreased
      bioaccessibility. Two main alternative hypotheses were put forward, either lower
      polarity led to higher incorporation of FAs with longer hydrophobic aliphatic
      chain and lower number of double bonds in the emulsion present in the
      bioaccessible fraction or enzymatic selectivity preferentially hydrolyzed some
      FAs on the basis of their structure or position in the triacylglycerol molecule. 

PMID- 25952869
TI  - Identification and quantification of anthocyanins in fruits from Neomitranthes
      obscura (DC.) N. Silveira an endemic specie from Brazil by comparison of
      chromatographic methodologies.
AB  - Neomitranthes obscura (DC.) N. Silveira is a Brazilian fruit belonging to the
      Myrtaceae family that contains anthocyanins in the peel and was studied for the
      first time in this work. Delphinidin-3-O-galactoside, delphinidin-3-O-glucoside,
      cyanidin-3-O-galactoside, cyanidin-3-O-glucoside, cyanidin-3-O-arabinoside,
      petunidin-3-O-glucoside, pelargonidin-3-O-glucoside, peonidin-3-O-galactoside,
      peonidin-3-O-glucoside, cyanidin-3-O-xyloside were separated and identified by
      LC/DAD/MS and by co-elution with standards. Reliable quantification of
      anthocyanins in the mature fruits was performed by HPLC/DAD using weighted linear
      regression model from 0.05 to 50mg of cyaniding-3-O-glucoside L(-1) because it
      gave better fit quality than least squares linear regression. Good precision and
      accuracy were obtained. The total anthocyanin content of mature fruits was 263.6
      +/- 8.2 mg of cyanidin-3-O-glucoside equivalents 100 g(-1) fresh weight, which
      was in the same range found in literature for anthocyanin rich fruits.

PMID- 25952870
TI  - Surfactant mediated extraction of total phenolic contents (TPC) and antioxidants
      from fruits juices.
AB  - The aim of this study was to enhance the extraction of total phenolic contents
      (TPC) and antioxidants from fruit juices by the application of surfactants
      formulations instead of conventional solvents (methanol, ethanol and acetone). A
      variety of fruit infusions: apple red delicious (apple (rd)) (Malus domestica),
      Mcintosh apple (apple (i)) (Malus pumila), sweet lemon (Citrus limetta) and mango
      (Magnifera indica) were studied. Effect of water, organic solvents and five
      different aqueous surfactant formulations viz. SDS, Brij-35, Brij-58, Triton X
      100 and Span-40 were explored for the extraction of TPC and determining the
      antioxidant activity (AA). The TPC and AA (%) were determined using Folin
      Ciocalteu (FCA) and DPPH assay, respectively. The effect of surfactant type,
      concentration and common organic solvents on the extraction of TPC and AA (%) was
      studied using UV-visible spectrophotometric technique. Among all the extracting
      systems employed, Brij-58 showed the highest extraction efficiency. 

PMID- 25952871
TI  - Xoconostle fruit (Opuntia matudae Scheinvar cv. Rosa) by-products as potential
      functional ingredients.
AB  - There is a lack of information on the potential use of xoconostle cultivars as
      sources of antioxidants for food, pharmaceutical and colorant industries. The aim
      of this study was to provide a phytochemical characterisation and antioxidant
      activity evaluation of Opuntia matudae Scheinvar cv. Rosa by-products (epicarp
      and endocarp mucilage's), in order to evaluate their interest as sources of
      functional ingredients for human or animal foods. These by-products showed a high
      content in glucose, citric and linoleic acids, tocopherols, and isorhamnetin-O
      (di-deoxyhexosyl-hexoside) (mainly in epicarp), and presented relevant
      antioxidant properties. The obtained results support the use of O. matudae
      Scheinvar cv. Rosa agro-industrial by-products as functional food ingredients,
      namely for antioxidant-enriched formulations, instead of being discarded. 

PMID- 25952872
TI  - Characterization of free, conjugated and bound phenolics and lipophilic
      antioxidants in regular- and non-darkening cranberry beans (Phaseolus vulgaris
      L.).
AB  - Cranberry beans (Phaseolus vulgaris L.) from 7 different cultivars were
      characterized for phytochemicals and assessed for antioxidant activities. In
      vitro colorimetric methods were used to measure total phenolic (TPC) and total
      proanthocyanidin (PAC) contents. Free, conjugated and bound phenolic acids and
      flavonoids were also identified and quantified using HPLC-DAD/ESI-MS(n). Regular
      darkening (RD) seeds contained higher TPC, PAC and flavonoids which were absent
      in the non-darkening (ND) seeds. Bound and conjugated phenolics in RD and ND
      mainly included cinnamic and benzoic acids. DPPH, FRAP and ORAC showed strong
      positive correlation with TPC, PAC, and with specific phenolics such as free
      catechin and bound p-hydroxybenzoic acid. Lipophilic extracts were rich in
      polyunsaturated fatty acids (69.20-76.89%). Carotenoid and tocopherol were
      limited to gamma-tocopherol and beta-carotene. Results from this study can
      contribute to the development of cranberry bean cultivars with increased health
      benefits and addresses specific phenolic contributors to antioxidant activity. 

PMID- 25952873
TI  - Complexes of green tea polyphenol, epigalocatechin-3-gallate, and 2S albumins of
      peanut.
AB  - 2S albumins of peanuts are seed storage proteins, highly homologous in structure
      and described as major elicitors of anaphylactic reactions to peanut (allergens
      Ara h 2 and Ara h 6). Epigallocatechin-3-gallate (EGCG) is the most biologically
      potent polyphenol of green tea. Non-covalent interactions of EGCG with proteins
      contribute to its diverse biological activities. Here we used the methods of
      circular dichroism, fluorescence quenching titration, isothermal titration
      calorimetry and computational chemistry to elucidate interactions of EGCG and 2S
      albumins. Similarity in structure and overall fold of 2S albumins yielded similar
      putative binding sites and similar binding modes with EGCG. Binding affinity
      determined for Ara h 2 was in the range described for complexes of EGCG and other
      dietary proteins. Binding of EGCG to 2S albumins affects protein conformation, by
      causing an alpha-helix to beta-structures transition in both proteins. 2S
      albumins of peanuts may be good carriers of physiologically active green tea
      catechin. 

PMID- 25952874
TI  - Effect of degree of milling on phenolic profiles and cellular antioxidant
      activity of whole brown rice.
AB  - The impact of increasing degree of milling (DOM) on free and bound phenolics and
      flavonoids and on cellular antioxidant activity (CAA) of japonica and indica
      brown rice was investigated. As the average DOM increased from 0 to 2.67, 7.25
      and 9.60%, the average total phenolic content decreased by 21.1, 42.6 and 55.6%,
      and the average total CAA value decreased by 37.4, 84.0 and 92.8%, respectively.
      Furthermore, the percentage contributions of bound forms to total phenolics and
      flavonoids decreased with increasing DOM. The contents of nine phenolic compounds
      significantly decreased with increasing DOM, including quercetin, ferulic and
      coumaric acids. Interestingly, as the DOM increased to 9.6%, free ferulic and
      coumaric acids were undetectable in japonica rice, while neither free nor bound
      caffeic acid was detectable in indica rice. These findings indicate that DOM
      should be carefully controlled for acceptable sensory quality and retention of
      phytochemicals during brown rice milling. 

PMID- 25952875
TI  - A unique quantitative method of acid value of edible oils and studying the impact
      of heating on edible oils by UV-Vis spectrometry.
AB  - UV-Vis spectroscopy coupled with chemometrics was used effectively to study the
      impact of heating on edible oils (corn oil, sunflower oil, rapeseed oil, peanut
      oil, soybean oil and sesame oil) and determine their acid value. Analysis of
      their first derivative spectra showed that the peak at 370 nm was a common
      indicator of the heated oils. Partial least squares regression (PLS) and
      principle component regression (PCR) were applied to building individual
      quantitative models of acid value for each kind of oil, respectively. The PLS
      models had a better performance than PCR models, with determination coefficients
      (R(2)) of 0.9904-0.9977 and root mean square errors (RMSE) of 0.0230-0.0794 for
      the prediction sets of each kind of oil, respectively. An integrate quantitative
      model built by support vector regression for all the six kinds of oils was also
      developed and gave a satisfactory prediction with a R(2) of 0.9932 and a RMSE of
      0.0656.

PMID- 25952876
TI  - Inter-laboratory validation study of two immunochemical methods for detection of
      processed ruminant proteins.
AB  - In order to facilitate safe re-introduction of non-ruminant processed animal
      proteins (PAPs) in aqua feed, two immunoassays have been tested in an
      interlaboratory study for their capability to detect ruminant PAPs processed
      under European conditions. The sensitivity of the MELISA-TEK assay was improved
      by applying a specific extraction kit. Six approved blank pork and poultry
      samples were adulterated to produce 15 samples spiked at 0.5%, 1.0% and 2.0% with
      ruminant material, sterilised at either 133  degrees C or 137  degrees C.
      Fourteen participants investigated the 6 blanks and 15 spiked samples, making 21
      samples for the final test. For both assays specificity and sensitivity were at
      97% or higher. Concordance and accordance were higher than 95% with one
      exception. The results indicate that both assays provided correct results at 0.5%
      and higher for the detecting ruminant PAPs (sterilised at 133  degrees C) in non
      ruminant PAPs. Given the 2% upper limit of ruminant PAPs in non-ruminant PAPs for
      avoiding an increase in BSE incidents, these methods are fit for monitoring non
      ruminant PAPs intended for aqua feed.

PMID- 25952877
TI  - Potential of high pressure homogenization to induce autolysis of wine yeasts.
AB  - High pressure homogenization (HPH) was tested for inducing autolysis in a
      commercial strain of Saccharomyces bayanus for winemaking. The effects on cell
      viability, the release of soluble proteins, glucidic colloids and amino acids in
      wine-like medium and the volatile composition of the autolysates were
      investigated after processing, in comparison with thermolysis. HPH seemed a
      promising technique for inducing autolysis of wine yeasts. One pass at 150 MPa
      was the best operating conditions. Soluble colloids, proteins and free amino
      acids were similar after HPH and thermolysis, but the former gave a more
      interesting volatile composition after processing, with higher concentrations of
      ethyl esters (fruity odors) and lower fatty acids (potential off-flavors). This
      might allow different winemaking applications for HPH, such as the production of
      yeast derivatives for wine ageing. In the conditions tested, HPH did not allow
      the complete inactivation of yeast cells; the treatment shall be optimized before
      winemaking use.

PMID- 25952878
TI  - Determination of polyphosphates in fish and shrimp muscles by capillary
      electrophoresis with indirect UV detection after phosphatase inhibition using
      high pressure pretreatment.
AB  - A method was proposed for the determination of polyphosphates (P2O7(4-), P3O10(5
      ) and (PO3)3(3-)) in fish and shrimp muscles by capillary electrophoresis with
      indirect UV detection after phosphatase inhibition using high pressure
      pretreatment (HPP). Separation parameters were optimized and the effects of HPP
      on deactivation of enzyme were investigated. Well resolution was obtained with 10
      mM adenosine 5'-phosphate (ATP) in 16 mM disodium hydrogen phosphate combining
      with 32 mM citric acid buffer (pH = 6.4) containing 0.1 mM cetyltrimethyl
      ammonium bromide, and phosphatase was effectively inhibited by HPP at 400 MPa for
      10 min. Method was validated with LOD (0.23-0.33 mg g(-1)) and LOQ (0.77-1.0 mg
      g(-1)). Recovery of P2O7(4-), P3O10(5-) and (PO3)3(3-) in the fortified samples
      were in the range of 91.6-100.1%, 97.6-104.6% and 79.1-88.1%, respectively, and
      the corresponding RSD ranged from 1.1% to 6.8%. Finally, the method was applied
      in the determination of polyphosphates in food samples collected from local
      markets.

PMID- 25952879
TI  - Application of integrated comprehensive/multidimensional gas chromatography with
      mass spectrometry and olfactometry for aroma analysis in wine and coffee.
AB  - Component coelution in chromatographic analysis complicates identification and
      attribution of individual odour-active volatile molecules in complex multi
      component samples. An integrated system incorporating comprehensive two
      dimensional gas chromatography (GC * GC) and multidimensional gas chromatography
      (MDGC), with flame ionisation, olfactometry and mass spectrometry detection was
      developed to circumvent data correlation across different systems. Identification
      of potent odorants in Shiraz wine and the headspace of ground coffee are
      demonstrated as selected applications. Multiple solid-phase microextraction
      (SPME) sampling with GC-O located odour-active regions; GC * GC established the
      complexity of odour-active regions; MDGC provided high-resolution separation for
      each region; simultaneous 'O' and MS detection completed the analysis for target
      resolved peaks. Seven odour regions in Shiraz were analysed with MDGC-O/MS
      detection, revealing 11 odour volatiles through matching of mass spectrometry and
      retention indices from both separating dimensions, including acetic acid; octen-3
      ol; ethyl octanoate; methyl-2-oxo-nonanoate; butanoic acid, 2-methylbutanoic
      acid, and 3-methylbutanoic acid; 3-(methylthio)-1-propanol; hexanoic acid; beta
      damascenone; and ethyl-3-phenylpropanoate. A capsicum odour in ground coffee was
      identified as 2-methoxy-3-isobutylpyrazine with a 5-fold increase in S/N of the
      odorant when acquired using a 6-time cumulative SPME sampling approach.

PMID- 25952880
TI  - Composition and microstructure of colostrum and mature bovine milk fat globule
      membrane.
AB  - The microstructures of colostrum and mature bovine milk fat globule membrane
      (MFGM) were investigated using confocal laser scanning microscopy (CLSM) at
      different temperatures, and the relationships between microstructure variations
      and the chemical compositions of the MFGM were also examined. Using a fluorophore
      labeled phospholipid probe, we found that non-fluorescent domains on the MFGM
      were positively correlated with the amount of sphingomyelin at both room (20 
      degrees C) and physiological (37  degrees C) temperatures. However, at the
      storage temperature (4  degrees C), there were more non-fluorescent domains on
      the MFGM. These results indicate that the heterogeneities in the MFGM are most
      likely to be the result of the lateral segregation of sphingomyelin at the room
      and physiological temperatures, and at the storage temperature, phospholipids
      with saturated fatty acids affect the formation of these domains.

PMID- 25952881
TI  - Nutrient composition and starch characteristics of Quercus glandulifera Bl. seeds
      from China.
AB  - The chemical composition and starch characteristics of acorn (Quercus
      glandulifera Bl.) were studied. The moisture content of acorn seeds was 7.55%.
      The crude fat, crude protein, dietary fiber, total ash, and nitrogen-free extract
      contents of acorn seed were 4.20%, 10.16%, 2.95%, 0.03%, and 82.66%,
      respectively, on a dry weight basis. Linoleic, oleic, and palmitic were the most
      predominant fatty acids. UFA:SFA and SFA:MUFA:PUFA ratios were 2.6:1 and
      1.25:1.34:1, respectively. The essential amino acid content from acorn seeds was
      low based on FAO reference values. Acorn seeds were a good source of Fe, Zn, and
      Mn. The contents of vitamins A and E were 1.40 mg RE/100g and 10.78 mg/100 g,
      respectively. Starch extracted from acorn seeds had round, triangle, and
      elliptical morphology with granule size of 3.3-126.2 MUm. The ratio between
      amylose and amylopectin contents was 25.39:72.94. Acorn starch had a typical A
      type crystal pattern with 23.53% relative crystallinity. The gelatinization
      temperature was 66.53  degrees C and the transition enthalpy was 4.33 J/g.

PMID- 25952882
TI  - Up-and-down-shaker-assisted dispersive liquid-liquid microextraction coupled with
      gas chromatography-mass spectrometry for the determination of fungicides in wine.
AB  - An up-and-down-shaker-assisted dispersive liquid-liquid microextraction (UDSA
      DLLME) method coupled with gas chromatography-mass spectrometry was developed for
      the determination of fungicides (cyprodinil, procymidone, fludioxonil,
      flusilazole, benalaxyl, and tebuconazole) in wine. The developed method requires
      11 MUL of 1-octanol without the need for dispersive solvents. The total
      extraction time was approximately 3 min. Under optimum conditions, the linear
      range of the method was 0.05-100 MUg L(-1) for all fungicides and the limit of
      detection was 0.007-0.025 MUg L(-1). The absolute and relative recoveries were 31
      83% and 83-107% for white wine, respectively, and 32-85% and 83-108% for red
      wine, respectively. The intra-day and inter-day precision were 0.5-7.5% and 0.7
      6.1%, respectively. Our developed method had good sensitivity and high extraction
      efficiency. UDSA-DLLME is a desirable method in terms of performance and speed.

PMID- 25952883
TI  - Cranberries (Oxycoccus quadripetalus) inhibit lipid metabolism and modulate
      leptin and adiponectin secretion in 3T3-L1 adipocytes.
AB  - It has previously been shown that lyophilized cranberries (LCB) decreased lipid
      accumulation in 3T3-L1 cells and inhibited preadipocyte differentiation by down
      regulation of the expression of key transcription factors (PPARgamma, C/EBPalpha,
      SREBP1) of the adipogenesis pathway. To elucidate the molecular basis of anti
      lipogenic activity of LCB, the expression of several genes involved in lipid
      metabolism, such as adipocyte fatty acid-binding protein (aP2), lipoprotein
      lipase (LPL), fatty acid synthase (FAS), hormone sensitive lipase (HSL) and
      perilipin 1 (PLIN1), was examined in the present study. Additionally, the effects
      of LCB on adiponectin and leptin expression and protein secretion were also
      investigated. LCB reduced lipid accumulation during preadipocyte differentiation
      by down-regulation of the mRNA level of aP2, FAS, LPL, HSL and PLIN1. Moreover,
      LCB decreased leptin gene expression and increased adiponectin gene expression
      and protein secretion in a dose-dependent manner. Therefore cranberries could be
      considered as bioactive factors, which are effective in the inhibition of adipose
      tissue mass production. 

PMID- 25952884
TI  - Filamentous fungi as a source of natural antioxidants.
AB  - Ten species of filamentous fungi grown in submerged flask cultures were
      investigated for antioxidant capacity. Effective antioxidant activity was
      demonstrated in terms of beta-carotene/linoleic acid bleaching, radical
      scavenging, reduction of metal ions and chelating abilities against ferrous ions.
      Different extraction methods affected antioxidant activities through their effect
      on biologically active compounds produced in fungal mycelia. The methanolic
      extract of each fungus was typically more effective in antioxidant properties.
      Phenolic content was established in the range of 0.44-9.33 mg/g, flavonoid
      contents were in the range of 0.02-3.90 mg/g and condensed tannin contents were
      in the range of 1.77-18.83 mg/g. Total phenol content of each extract was
      attributed to overall antioxidant capacity (r ? 0.883-1.000). Submerged
      cultivation of Grifola frondosa, Monascus purpureus, Pleurotus spp., Lentinula
      edodes and Trametes versicolor proved to be an effective method for the
      production of natural antioxidants.

PMID- 25952885
TI  - Surfacted ferrofluid based dispersive solid phase extraction; a novel approach to
      preconcentration of cationic dye in shrimp and water samples.
AB  - Surfacted ferrofluid (S-FF) is a stable colloid dispersion of magnetic
      nanoparticles in a carrier liquid which possesses magnetic properties and
      fluidity simultaneously. Specifically in S-FF coating magnetic nanoparticles with
      a suitable surfactant provides steric repulsions to prevent particles
      agglomeration. Selecting the function of surfactant can be engineered according
      to its application. In the present study, for the first time the application of S
      FF in dispersive solid phase extraction of methylene blue (as a cationic dye
      model) in water and shrimp samples was investigated. For this purpose, in order
      to use ionic liquid as carrier fluid, the surface of Fe3O4 nanoparticles was
      coated by an anionic surfactant in a polar medium to form a hydrophilic layer
      around magnetic nanoparticles. In addition to hydrophobic interactions between
      the analyte and carbonic chain of surfactant, the retention of cationic dye was
      mainly governed by attractive electrostatic interactions between polar head of
      surfactant and dye. Under optimized conditions, the relative standard deviation
      is 2.9%, the limit of detection is 2.5 MUg L(-1), and the preconcentration factor
      is 135.

PMID- 25952887
TI  - Replacement of fish oil with a DHA-rich algal meal derived from Schizochytrium
      sp. on the fatty acid and persistent organic pollutant levels in diets and flesh
      of Atlantic salmon (Salmo salar, L.) post-smolts.
AB  - The replacement of fish oil (FO) with a DHA-rich Schizochytrium sp. algal meal
      (AM) at two inclusion levels (11% and 5.5% of diet) was tested in Atlantic salmon
      post-smolts compared to fish fed a FO diet of northern (NFO) or southern
      hemisphere (SFO) origin. Fish were preconditioned prior to the 19-week
      experimental feeding period to reduce long-chain polyunsaturated fatty acid (LC
      PUFA) and persistent organic pollutant levels (POPs). Dietary POP levels differed
      significantly between treatments in the order of NFO>SFO>11 AM/5.5 AM and were
      subsequently reflected in the flesh. Fish fed the 11 AM diet contained similar
      DHA levels (g 100 g(-1) flesh) to FO-fed fish, despite percentage differences.
      However, the low levels of EPA in the diets and flesh of algal-fed fish
      compromised the overall nutritional value to the final consumer. Nevertheless,
      further developments in microalgae culture offer a promising alternative lipid
      source of LC-PUFA to FO in salmon feeds that warrants further investigation.

PMID- 25952886
TI  - Impact of cell wall encapsulation of almonds on in vitro duodenal lipolysis.
AB  - Although almonds have a high lipid content, their consumption is associated with
      reduced risk of cardiovascular disease. One explanation for this paradox could be
      limited bioaccessibility of almond lipids due to the cell wall matrix acting as a
      physical barrier to digestion in the upper gastrointestinal tract. We aimed to
      measure the rate and extent of lipolysis in an in vitro duodenum digestion model,
      using raw and roasted almond materials with potentially different degrees of
      bioaccessibility. The results revealed that a decrease in particle size led to an
      increased rate and extent of lipolysis. Particle size had a crucial impact on
      lipid bioaccessibility, since it is an indicator of the proportion of ruptured
      cells in the almond tissue. Separated almond cells with intact cell walls showed
      the lowest levels of digestibility. This study underlines the importance of the
      cell wall for modulating lipid uptake and hence the positive health benefits
      underlying almond consumption. 

PMID- 25952888
TI  - Flavor characteristic analysis of soymilk prepared by different soybean cultivars
      and establishment of evaluation method of soybean cultivars suitable for soymilk
      processing.
AB  - Flavor is an essential quality characteristics of soymilk, which contains
      volatile compounds derived from fatty acids via enzymatic and thermal reactions.
      In this study, 67 kinds of soybean cultivars were selected, and correlation
      analysis was conducted between physicochemical indexes of these soybean cultivars
      and flavor characteristic indexes of soymilk. With clustering analysis, all the
      soybean cultivars could be classified into three classes, and according to the
      results of principal component analysis for each class of soymilk flavor
      characteristics, the soymilk of second class had relatively heavier beany and non
      beany flavor, and the third class had weaker flavor. For soybean cultivars of
      which the soymilk characteristics were unknown, two discriminant functions could
      be used to predict flavor characteristics if the physicochemical indexes were
      known. Therefore, screening of soybean cultivars suitable for soymilk processing
      can be targeted for the flavor favored by consumers and an evaluation method
      established. 

PMID- 25952889
TI  - A sensitive molecularly imprinted polymer based quartz crystal microbalance
      nanosensor for selective determination of lovastatin in red yeast rice.
AB  - Lovastatin (LOV) is a statin, used to lower cholesterol which has been found as a
      hypolipidemic agent in commercial red yeast rice. In present study, a sensitive
      molecular imprinted quartz crystal microbalance (QCM) sensor was prepared by
      fabricating a self-assembling monolayer formation of allylmercaptane on QCM chip
      surface for selective determination of lovastatin (LOV) in red yeast rice. To
      prepare molecular imprinted quartz crystal microbalance (QCM) nanosensor, LOV
      imprinted poly(2-hydroxyethyl methacrylate-methacryloylamidoaspartic acid)
      [p(HEMA-MAAsp)] nanofilm was attached on the modified gold surface of QCM chip.
      The non-modified and improved surfaces were characterized by using contact angle,
      atomic force microscopy (AFM) and Fourier transform infrared (FTIR) spectroscopy.
      The imprinted QCM sensor was validated according to the ICH guideline
      (International Conference on Harmonisation). The linearity range was obtained as
      0.10-1.25 nM. The detection limit of the prepared material was calculated as
      0.030 nM. The developed QCM nanosensor was successfully used to examine red yeast
      rice. Furthermore, the stability and repeatability of the prepared QCM nanosensor
      were studied. The spectacular long-term stability and repeatability of the
      prepared LOV-imprinted QCM nanosensor make them intriguing for use in QCM
      sensors.

PMID- 25952890
TI  - Trans fatty acid content in Serbian margarines: Urgent need for legislative
      changes and consumer information.
AB  - This study examined the fatty acid (FA) composition of 13 (7 soft and 6 hard)
      Serbian margarines. Significantly higher amounts of trans fatty acids (TFA) were
      found in hard margarines (up to 28.84% of total FA), than in soft ones (0.17
      6.89%). Saturated FA (SFA) were present with 22.76-51.17%. Oleic acid ranged from
      26.78% to 43.78%. The proportion of polyunsaturated FA (PUFA) was 22.15-49.29% in
      soft margarines, but only 8.02-15.28% in hard margarines, probably due to the
      hydrogenisation process. The atherogenic and thrombogenic indexes (AI and TI,
      respectively) in soft margarines were relatively low (AI 0.23-0.63 and TI 0.44
      0.97), but in hard margarines AI and particularly TI were high (1.03-1.67 and
      1.96-3.04, respectively). These findings suggest that FA composition of Serbian
      margarines should be improved by replacing atherogenic TFA and SFA with
      beneficial ones, in order to avoid adverse effects on health. Therefore
      legislative changes and consumer information are urgently needed. 

PMID- 25952891
TI  - Low level of selenium increases the efficacy of 24-epibrassinolide through
      altered physiological and biochemical traits of Brassica juncea plants.
AB  - This study was conducted to provide an insight into the effect of Se (through
      soil) induced changes in Brassica juncea plants in the presence and absence of 24
      epibrassinolide (EBL; foliar). The Se treatments showed dual response, 10 MUM of
      Se significantly increased growth, water relations, photosynthetic attributes
      along with carbonic anhydrase activity whereas its higher concentrations proved
      inhibitory in concentration dependent manner. The follow-up application of EBL to
      the Se stressed plants improved growth, water relations, photosynthesis and
      simultaneously enhanced the various antioxidant enzymes viz. catalase, peroxidase
      and superoxide dismutase with the excess accumulation of proline. In addition to
      this, 10 MUM Se increases the efficacy of 10(-8) M of EBL and both in combination
      showed maximum increase for the growth and photosynthetic traits of plants. On
      the other hand, the elevated level of antioxidant enzymes as well as proline
      could have conferred tolerance to the Se-stressed plants resulting in improved
      growth, water relations and photosynthesis.

PMID- 25952892
TI  - Comparison of five analytical methods for the determination of peroxide value in
      oxidized ghee.
AB  - In the present study, a comparison of five peroxide analytical methods was
      performed using oxidized ghee. The methods included the three iodometric
      titration viz. Bureau of Indian Standard (BIS), Association of Analytical
      Communities (AOAC) and American Oil Chemists' Society (AOCS), and two
      colorimetric methods, the ferrous xylenol orange (FOX) and ferric thiocyanate
      (International Dairy Federation, IDF) methods based on oxidation of iron. Six
      ghee samples were stored at 80  degrees C to accelerate deterioration and sampled
      periodically (every 48 h) for peroxides. Results were compared using the five
      methods for analysis as well as a flavor score (9 point hedonic scale). The
      correlation coefficients obtained using the different methods were in the order:
      FOX (-0.836) > IDF (-0.821) > AOCS (-0.798) > AOAC (-0.795) > BIS (-0.754). Thus,
      among the five methods used for determination of peroxide value of ghee during
      storage, the highest coefficient of correlation was obtained for the FOX method.
      The high correlations between the FOX and flavor data indicated that FOX was the
      most suitable method tested to determine peroxide value in oxidized ghee.

PMID- 25952893
TI  - Effect of germination on the physicochemical and antioxidant characteristics of
      rice flour from three rice varieties from Nigeria.
AB  - This study determined the effect of germination (48 h) on the physicochemical and
      antioxidant characteristics of rice flour from three rice varieties from Nigeria.
      Local rice varieties (Jamila, Jeep and Kwandala) were evaluated and compared to
      an improved variety (MR 219). Physicochemical and antioxidant properties of
      flours were determined using standard methods. Protein, magnesium, phosphorus,
      potassium and antioxidant properties of rice flours increased after germination
      while phytic acid and total starch contents decreased. Foaming capacity and
      stability of rice flours increased after germination. Germination resulted to
      changes in pasting and thermal characteristics of rice flours. Germinated rice
      flours had better physicochemical and antioxidant properties with reduced phytic
      acid and starch contents compared to MR 219, which can be utilized as functional
      ingredients in the preparation of rice-based products.

PMID- 25952894
TI  - Oxidative changes and weakened gelling ability of salt-extracted protein are
      responsible for textural losses in dumpling meat fillings during frozen storage.
AB  - The objective of the study was to investigate the contribution of oxidation and
      rheological behaviour of proteins present outside the meat particle (OMP) and
      those remaining inside the meat particle (IMP) in dumpling meat fillings. The -7 
      degrees C sample fillings stored for 180 d had a significantly lower breaking
      strength and water-holding capacity than those stored at -18  degrees C and -7 
      degrees C/-18  degrees C (P < 0.05). Microscopy of stained samples showed
      significant fat exudation in the high (-7  degrees C) and fluctuating (-7 
      degrees C/-18  degrees C) temperature treatments during storage, coinciding with
      decreased thermal stability of OMP. There was a more abundant carbonyl production
      in OMP than in IMP (P < 0.05). The storage modulus G' in OMP was significantly
      lower than that in IMP. Moreover, SDS-PAGE showed that -7  degrees C and -7 
      degrees C/-18  degrees C samples produced more insoluble protein aggregates.
      These findings indicate that oxidative damage and reduced gelling potential of
      OMP proteins led to reduced textural properties in frozen dumplings.

PMID- 25952895
TI  - Oil-in-water emulsion gels stabilized with chia (Salvia hispanica L.) and cold
      gelling agents: Technological and infrared spectroscopic characterization.
AB  - This paper reports on the development of olive oil-in-water emulsion gels
      containing chia (Salvia hispanica L.) (flour or seed) and cold gelling agents
      (transglutaminase, alginate or gelatin). The technological and structural
      characteristics of these emulsion gels were evaluated. Both structural and
      technological changes in emulsion gels resulting from chilled storage were also
      determined. The color and texture of emulsion gels depend on both the cold
      gelling agents used and chilled storage. Lipid oxidation increased (p < 0.05)
      during storage in emulsion gels containing transglutaminase or alginate. Analyses
      of the half-bandwidth of the 2923 cm(-1) band and the area of the 3220 cm(-1)
      band suggest that the order/disorder of the oil lipid chain related to lipid
      interactions and droplet size in the emulsion gels could be decisive in
      determining their textural properties. The half-bandwidth of 2923 cm(-1) band and
      area of 3220 cm(-1) band did not show significant differences during chilled
      storage.

PMID- 25952896
TI  - Determination of leucomalachite green, leucocrystal violet and their chromic
      forms using excitation-emission matrix fluorescence coupled with second-order
      calibration after dispersive liquid-liquid microextraction.
AB  - A novel spectrofluorimetric method has been developed for the simultaneous
      determination of leucomalachite green (LMG), leucocrystal violet (LCV), malachite
      green (MG) and crystal violet (CV) by combining the sensitivity of molecular
      fluorescence and the selectivity of the second-order calibration. Residues of
      LMG, LCV, MG and CV were simultaneously extracted from fish and shrimp muscle
      with acetonitrile. The non-fluorescent CV and MG were then reduced to the
      corresponding fluorescent LMG and LCV by reacting with sodium borohydride. After
      preconcentration with dispersive liquid-liquid microextraction technique, the
      extracts were analyzed by using excitation-emission matrix fluorescence coupled
      with second-order calibration methods based on parallel factor analysis (PARAFAC)
      and alternating trilinear decomposition (ATLD) algorithms. The limits of
      detection obtained were 2.21-2.65 ng g(-1) by PARAFAC and 2.30-2.86 ng g(-1) by
      ATLD, respectively. The developed method was successfully applied to simultaneous
      determination of the four analytes in grass carp and shrimp samples with
      recoveries of 90.53-103.03% for PARAFAC and 90.40-102.75% for ATLD. The accuracy
      of this novel method was also verified by high performance liquid chromatography.

PMID- 25952897
TI  - Determination of metals in soft drinks packed in different materials by ETAAS.
AB  - The present work proposes a method for the direct determination of Al, Cu, Cr, Fe
      and Ni in Brazilian carbonated soft drinks by electrothermal atomic absorption
      spectrometry (ETAAS). Samples of different flavors packed in containers made of
      different materials (polyterephthalate ethylene and glass bottles, and aluminum
      and steel cans) were analyzed. The method was optimized by building up pyrolysis
      and atomization curves in sample medium and by evaluating the calibration
      approach. Under optimized conditions, recoveries in the range of 92-104% were
      obtained in the evaluation of method accuracy. The limits of quantification for
      Al, Cu, Cr, Fe and Ni were 2.3, 0.93, 0.17, 0.90 and 1.2 MUg L(-1), respectively.
      Also, the impact of the material used in the packaging and flavor on the
      concentrations of each metal in the samples was evaluated. It was proved that
      neither flavor nor packaging material affected the concentrations of Al and Fe in
      the samples. On the other hand, the packaging material influenced the
      concentration of Cu, Cr and Ni, and only the flavor affected the concentration of
      Cu in the samples. These conclusions were based on the data obtained from the
      application of a two-way ANOVA evaluation at 95% confidence level.

PMID- 25952898
TI  - Proteomics analysis in frozen horse mackerel previously high-pressure processed.
AB  - The effect of high-pressure processing (HPP) (150, 300 and 450 MPa for 0, 2.5 and
      5 min) on total sodium dodecyl sulphate (SDS)-soluble and sarcoplasmic proteins
      in frozen (-10  degrees C for 3 months) horse mackerel (Trachurus trachurus) was
      evaluated. Proteomics tools based on image analysis of SDS-PAGE protein gels and
      protein identification by tandem mass spectrometry (MS/MS) were applied. Although
      total SDS-soluble fraction indicated no important changes induced by HPP, this
      processing modified the 1-D SDS-PAGE sarcoplasmic patterns in a direct-dependent
      manner and exerted a selective effect on particular proteins depending on
      processing conditions. Thus, application of the highest pressure (450 MPa)
      provoked a significant degradation of phosphoglycerate mutase 2, glycogen
      phosphorylase muscle form, pyruvate kinase muscle isozyme, beta-enolase and
      triosephosphate isomerase and phosphoglucomutase-1. Conversely, protein bands
      assigned to tropomyosin alpha-1 chain, fast myotomal muscle troponin T and
      parvalbumin beta 2 increased their intensity after applying a 450-MPa processing.

PMID- 25952899
TI  - Direct FTIR analysis of isolated trans fatty acids in edible oils using
      disposable polyethylene film.
AB  - A new transmission-based Fourier transform infrared (FTIR) spectroscopy method
      has been developed to determine trans fatty acids (TFA) content in edible oils
      using disposable polyethylene (PE) film as a spectral acquisition accessory.
      Calibration standards were devised by gravimetrically adding TFA to TFA-free oil.
      The response was measured at 990-945 cm(-1) against the baseline. A linear
      relationship between the areas in the spectral regions 1670-1625 cm(-1) and 990
      945 cm(-1) in TFA-free oil samples was established to compensate for interference
      due to underlying triacylglycerol absorptions in the trans measurement region
      (990-945 cm(-1)). Subsequently, the area measured at 990-945 cm(-1) was corrected
      for interference, using the linear equation obtained, to determine TFA content.
      Results indicated that the PE film-based FTIR method for analyzing TFA content in
      edible oils was simple and rapid, and could be used effectively as an alternative
      to gas chromatography and mass spectrometry methods.

PMID- 25952900
TI  - Evaluation on levels and conversion profiles of DON, 3-ADON, and 15-ADON during
      bread making process.
AB  - The present study investigated the changes and conversion profiles of DON, its
      conjugations 3-ADON, and 15-ADON during bread making process, by spiking targeted
      mycotoxin standards to Fusarium mycotoxins-free wheat flour. No significant (p <
      0.05) changes of DON levels were observed during dough preparation stages,
      including kneading, fermentation, and proofing. A reduction of DON level ranged
      from 4% to 14% was observed during baking process. The main thermal degradation
      products of DON, namely norDON A, B, C, and F were detected in the bread crust.
      Regarding ADONs, decreases of 20-40% for 3-ADON and 28-60% for 15-ADON were found
      during fermentation stage, and further losses of ADONs were observed after
      proofing process. Although ADONs levels gained an increase after baking. This
      study demonstrated that ADONs were converted to DON, while no ADONs were
      detectable in DON spiked samples during bread making process. The mechanism that
      ADONs could be converted into DON is unclear so far.

PMID- 25952901
TI  - Isthmin is a novel vascular permeability inducer that functions through cell
      surface GRP78-mediated Src activation.
AB  - AIMS: Isthmin (ISM) is a recently identified 60 kDa secreted angiogenesis
      inhibitor. Two cell-surface receptors for ISM have been defined, the high
      affinity glucose-regulated protein 78 kDa (GRP78) and the low-affinity
      alphavbeta5 integrin. As alphavbeta5 integrin plays an important role in
      pulmonary vascular permeability (VP) and ISM is highly expressed in mouse lung,
      we sought to clarify the role of ISM in VP. METHODS AND RESULTS: Recombinant ISM
      (rISM) dose-dependently enhances endothelial monolayer permeability in vitro and
      local dermal VP when administered intradermally in mice. Systemic rISM
      administration through intravenous injection leads to profound lung vascular
      hyperpermeability but not in other organs. Mechanistic investigations using
      molecular, biochemical approaches and specific chemical inhibitors revealed that
      ISM-GRP78 interaction triggers a direct interaction between GRP78 and Src,
      leading to Src activation and subsequent phosphorylation of adherens junction
      proteins and loss of junctional proteins from inter-endothelial junctions,
      resulting in enhanced VP. Dynamic studies of Src activation, VP and apoptosis
      revealed that ISM induces VP directly via Src activation while apoptosis
      contributes indirectly only after prolonged treatment. Furthermore, ISM is
      significantly up-regulated in lipopolysaccharide (LPS)-treated mouse lung.
      Blocking cell-surface GRP78 by systemic infusion of anti-GRP78 antibody
      significantly attenuates pulmonary vascular hyperpermeability in LPS-induced
      acute lung injury (ALI) in mice. CONCLUSION: ISM is a novel VP inducer that
      functions through cell-surface GRP78-mediated Src activation as well as induction
      of apoptosis. It induces a direct GRP78-Src interaction, leading to cytoplasmic
      Src activation. ISM contributes to pulmonary vascular hyperpermeability of LPS
      induced ALI in mice.

PMID- 25952902
TI  - Perlecan heparan sulfate deficiency impairs pulmonary vascular development and
      attenuates hypoxic pulmonary hypertension.
AB  - AIMS: Excessive vascular cell proliferation is an important component of
      pulmonary hypertension (PH). Perlecan is the major heparan sulfate (HS)
      proteoglycan in the vascular extracellular matrix. It binds growth factors,
      including FGF2, and either restricts or promotes cell proliferation. In this
      study, we have explored the effects of perlecan HS deficiency on pulmonary
      vascular development and in hypoxia-induced PH. METHODS AND RESULTS: In normoxia,
      Hspg2(Delta3/Delta3) mice, deficient in perlecan HS, had reduced pericytes and
      muscularization of intra-acinar vessels. Pulmonary angiography revealed a
      peripheral perfusion defect. Despite these abnormalities, right ventricular
      systolic pressure (RVSP) and myocardial mass remained normal. After 4 weeks of
      hypoxia, increases in the proportion of muscularized vessels, RVSP, and right
      ventricular hypertrophy were significantly less in Hspg2(Delta3/Delta3) compared
      with wild type. The early phase of hypoxia induced a significantly lower increase
      in fibroblast growth factor receptor-1 (FGFR1) protein level and receptor
      phosphorylation, and reduced pulmonary artery smooth muscle cell (PASMC)
      proliferation in Hspg2(Delta3/Delta3). At 4 weeks, FGF2 mRNA and protein were
      also significantly reduced in Hspg2(Delta3/Delta3) lungs. Ligand and carbohydrate
      engagement assay showed that perlecan HS is required for HS-FGF2-FGFR1 ternary
      complex formation. In vitro, proliferation assays showed that PASMC proliferation
      is reduced by selective FGFR1 inhibition. PASMC adhesion to fibronectin was
      higher in Hspg2(Delta3/Delta3) compared with wild type. CONCLUSIONS: Perlecan HS
      chains are important for normal vascular arborization and recruitment of
      pericytes to pulmonary vessels. Perlecan HS deficiency also attenuates hypoxia
      induced PH, where the underlying mechanisms involve impaired FGF2/FGFR1
      interaction, inhibition of PASMC growth, and altered cell-matrix interactions.

PMID- 25952903
TI  - Spine Posture and Discomfort During Prolonged Simulated Driving With Self
      Selected Lumbar Support Prominence.
AB  - OBJECTIVE: We examined magnitude preference, subjective discomfort, and spine
      posture during prolonged simulated driving with a self-selected amount of lumbar
      support. BACKGROUND: The general use of lumbar supports has been associated with
      decreased reports of low-back pain during driving exposures; however, minimal
      data exist regarding occupant magnitude preference. METHOD: Participants chose
      between five discrete levels of lumbar support (0-4 cm). Time-varying postural
      and discomfort responses were then monitored throughout 2 hr of simulated
      driving. RESULTS: There were no significant effects of gender or time on posture.
      Women preferred larger amounts of support than men (3.25 cm +/- 0.71 and 2.56 cm
      +/- 0.88, respectively, p = .048). All participants exhibited significant
      increases (p = .003) in pelvic discomfort throughout the 2-hr trial regardless of
      the level of support chosen. Discomfort related to various aspects of the lumbar
      support increased significantly over time. Retrospectively, no participants
      desired a setting beyond 4 cm, and the majority of respondents indicate had they
      been able to change their initial selection, they would choose a setting between
      2 and 3 cm. CONCLUSION: The results suggest that occupants would prefer
      increasing the excursion capability of automobile lumbar supports beyond 2 cm.
      APPLICATION: Excursion capability and adjustability of automobile lumbar supports
      are important features to better meet end-user preference and to reducing lumbar
      flexion in sitting.

PMID- 25952904
TI  - Prevalence of psychoactive substance use among youth in Rwanda.
AB  - BACKGROUND: Substance use among youth is a significant public health concern
      worldwide. However, little is known in Rwanda about the prevalence of drug use
      among youth. The goal of the current study was to assess the prevalence and
      determinants of substance use among youth in Rwanda. METHODS: A cross-sectional
      home survey was carried out with 2479 Rwandan youth. Youth ranging, in age from
      14-35 years, were randomly selected from 20 out of the 30 districts in the
      country. The youth were interviewed using a questionnaire that included socio
      demographic information and self-reported substance use. Misuse and dependence on
      alcohol, marijuana and tobacco were respectively assessed by the Alcohol Use
      Disorders Identification Test (AUDIT), the Cannabis Abuse Screening Test (CAST),
      and the Hooked on Nicotine Checklist (HONC). RESULTS: Overall, the prevalence
      rate of substance use over the month prior to the survey was 34% for alcohol,
      8.5% for tobacco smoking, 2.7% for cannabis, 0.2% for glue and 0.1% for drugs
      such as diazepam. 7.46% (one in thirteen) of the youth were alcohol dependent,
      4.88% (one in twenty) were nicotine dependent, and 2.54% (one in forty) dependent
      on cannabis. CONCLUSIONS: Our findings demonstrate that tobacco, alcohol,
      marijuana and other substance use are realities in the daily lives of youth in
      Rwanda. Further research is needed to monitor the evolution of this phenomenon
      and its determinants and in order to initiate evidenced-based interventions.

PMID- 25952906
TI  - Insulin increases glomerular filtration barrier permeability through PKGIalpha
      dependent mobilization of BKCa channels in cultured rat podocytes.
AB  - Podocytes are highly specialized cells that wrap around glomerular capillaries
      and comprise a key component of the glomerular filtration barrier. They are
      uniquely sensitive to insulin; like skeletal muscle and fat cells, they exhibit
      insulin-stimulated glucose uptake and express glucose transporters. Podocyte
      insulin signaling is mediated by protein kinase G type I (PKGI), and it leads to
      changes in glomerular permeability to albumin. Here, we investigated whether
      large-conductance Ca2+-activated K+ channels (BKCa) were involved in insulin
      mediated, PKGIalpha-dependent filtration barrier permeability. Insulin-induced
      glomerular permeability was measured in glomeruli isolated from Wistar rats.
      Transepithelial albumin flux was measured in cultured rat podocyte monolayers.
      Expression of BKCa subunits was detected by RT-PCR. BKCa, PKGIalpha, and upstream
      protein expression were examined in podocytes with Western blotting and
      immunofluorescence. The BKCa-PKGIalpha interaction was assessed with co
      immunoprecipitation. RT-PCR showed that primary cultured rat podocytes expressed
      mRNAs that encoded the pore-forming alpha subunit and four accessory beta
      subunits of BKCa. The BKCa inhibitor, iberiotoxin (ibTX), abolished insulin
      dependent glomerular albumin permeability and PKGI-dependent transepithelial
      albumin flux. Insulin-evoked albumin permeability across podocyte monolayers was
      also blocked with BKCa siRNA. Moreover, ibTX blocked insulin-induced disruption
      of the actin cytoskeleton and changes in the phosphorylation of PKG target
      proteins, MYPT1 and RhoA. These results indicated that insulin increased
      filtration barrier permeability through mobilization of BKCa channels via PKGI in
      cultured rat podocytes. This molecular mechanism may explain podocyte injury and
      proteinuria in diabetes.

PMID- 25952907
TI  - Mesh for prolapse surgery: Why the fuss?
AB  - Pelvic organ prolapse is a common gynaecological problem. Surgical techniques to
      repair prolapse have been constantly evolving to reduce the recurrence of
      prolapse and need for reoperation. Grafts made of synthetic and biological
      materials became popular in the last decade as they were intended to provide
      extra support to native tissue repairs. However, serious complications related to
      use of synthetic meshes have been reported and there is increasing medico-legal
      concern about mesh use in prolapse surgery. Some mesh products already have been
      withdrawn from the market and the FDA has introduced stricter surveillance of new
      and existing products. Large randomized studies comparing mesh with non-mesh
      procedures are lacking which creates uncertainty for the surgeon and their
      patients.The small cohorts of the RCTs available with short follow-up periods
      just allow the conclusion that the mesh repair can be helpful in the short to
      medium term but unfortunately are not able to prove safety for all patients. In
      particular, current clinical reports cannot define for which indication what
      material may be superior compared to non-mesh repair.Quality control through long
      term individual and national mesh registries is needed to keep a record of all
      surgeons using mesh and all devices being used, monitoring their effectiveness
      and safety data. Meshes with better biocompatibility designed specifically for
      use in vaginal surgery may provide superior clinical results, where the reduction
      of complications may allow a wider range of indications. 

PMID- 25952905
TI  - Mechanism for increased hepatic glycerol synthesis in the citrin/mitochondrial
      glycerol-3-phosphate dehydrogenase double-knockout mouse: Urine glycerol and
      glycerol 3-phosphate as potential diagnostic markers of human citrin deficiency.
AB  - The mitochondrial aspartate-glutamate carrier isoform 2 (citrin) and
      mitochondrial glycerol-3-phosphate dehydrogenase (mGPD) double-knockout mouse has
      been a useful model of human citrin deficiency. One of the most prominent
      findings has been markedly increased hepatic glycerol 3-phosphate (G3P) following
      oral administration of a sucrose solution. We aimed to investigate whether this
      change is detectable outside of the liver, and to explore the mechanism
      underlying the increased hepatic G3P in these mice. We measured G3P and its
      metabolite glycerol in plasma and urine of the mice under various conditions.
      Glycerol synthesis from fructose was also studied using the liver perfusion
      system. The citrin/mGPD double-knockout mice showed increased urine G3P and
      glycerol under normal, fed conditions. We also found increased plasma glycerol
      under fasted conditions, while oral administration of different carbohydrates or
      ethanol led to substantially increased plasma glycerol. Fructose infusion to the
      perfused liver of the double-knockout mice augmented hepatic glycerol synthesis,
      and was accompanied by a concomitant increase in the lactate/pyruvate (L/P)
      ratio. Co-infusion of either pyruvate or phenazine methosulfate, a cytosolic
      oxidant, with fructose corrected the high L/P ratio, leading to reduced glycerol
      synthesis. Overall, these findings suggest that hepatic glycerol synthesis is
      cytosolic NADH/NAD(+) ratio-dependent and reveal a likely regulatory mechanism
      for hepatic glycerol synthesis following a high carbohydrate load in citrin
      deficient patients. Therefore, urine G3P and glycerol may represent potential
      diagnostic markers for human citrin deficiency. 

PMID- 25952908
TI  - Transcriptome profiling of trichome-less reveals genes associated with
      multicellular trichome development in Cucumis sativus.
AB  - Trichomes on plants, similar to fine hairs on animal and human bodies, play
      important roles in plant survival and development. They also represent a useful
      model for the study of cell differentiation. Although the regulatory gene network
      of unicellular trichome development in Arabidopsis thaliana has been well
      studied, the genes that regulate multicellular trichome development remain
      unclear. We confirmed that Cucumis sativus (cucumber) trichomes are multicellular
      and unbranched, but identified a spontaneous mutant, trichome-less (tril), which
      presented a completely glabrous phenotype. We compared the transcriptome
      profilings of the tril mutant and wild type using the Illumina HiSeq 2000
      sequencing technology. A total of 991 genes exhibited differential expression:
      518 were up-regulated and 473 were down-regulated. We further identified 62
      differentially expressed genes that encoded crucial transcription factors and
      were subdivided into seven categories: homeodomain, MADS, MYB, and WRKY domains,
      ethylene-responsive, zinc finger, and other transcription factor genes. We
      further analyzed the tissue-expression profiles of two candidate genes, GLABRA2
      like and ATHB51-like, using qRT-PCR and found that these two genes were
      specifically expressed in the epidermis and trichomes, respectively. These
      results and the tril mutant provide useful tools to study the molecular networks
      associated with multicellular trichome development. 

PMID- 25952909
TI  - Correlation between the level of physical activity as measured by accelerometer
      and the Harris Hip Score.
AB  - BACKGROUND: The most widely used method to assess the outcome of total hip
      arthroplasty (THA) is the Harris Hip Score (HHS). Patients' expectations about
      the benefits of hip arthroplasty are increasing and are no longer limited to pain
      reduction. Patients believe they will be able to do recreational activity and
      sport after surgery. It is also essential to assess the level of physical
      activity after arthroplasty insofar as it is associated with early failure of the
      components. The purpose of this study is to explore correlation of the HHS with
      physical activity in patients with THA. METHODS: This is a cross-sectional study
      on 47 patients with THA. Correlation of HHS with the results of physical activity
      obtained objectively using accelerometer worn for a week and subjectively using
      the IPAQ questionnaire and the UCLA scale. FINDING: There was no correlation
      between the HHS and the activity measured using accelerometers, or with the IPAQ
      activity questionnaire. The HHS reported moderately significant correlations with
      the UCLA scale. CONCLUSIONS: The HHS may not be as discriminatory as other
      instruments at assessing patient activity levels after THA.

PMID- 25952910
TI  - Epidermolysis bullosa acquisita of MRSA skin carrier: a case of successful total
      hip arthroplasty.
AB  - PURPOSE: Epidermolysis bullosa acquisita (EBA) is a very rare disease of a
      chronic autoimmune subepidermal blistering, usually manifesting as skin
      fragility, blisters and erosions. In this article, we report a successful THA in
      a patient with osteonecrosis of the femoral head with EBA and methicillin
      resistant staphylococcus aureus (MRSA) skin carriage. METHODS: A 59-year-old
      woman had severe and debilitating left hip pain due to osteonecrosis of the
      femoral head. She had suffered from EBA for the past 7 years. She had received
      several courses of intravenous steroid pulse therapy in the past, and taking 6 mg
      of prednisone and 100 mg of minocycline per day for infected skin blisters.
      Severe blisters and scars covered her body, especially at the prone area. A
      bacteriological examination taken using a cotton-swab returned MRSA at the nasal
      cavity and anterolateral part of the proximal femur. RESULTS: We employed an
      antibiotic prophylactic protocol used for one-stage revision for infected hip
      prosthesis. Primary THA was performed using the anterior approach with antibiotic
      loaded cement, and the skin was fully covered with a soft and conformable foam
      dressing.1-year post-op, there are no signs of infection. The Harris Hip Score
      improved from 37 pre-op to 93.4 at 1 year post-op. CONCLUSIONS: Although care
      must be taken by medical professionals to avoid the prescription of unnecessary
      antibiotics, when used appropriately, there appears to be substantial benefits to
      be gained in the field of joint replacement for patients who are at high risk of
      infection.

PMID- 25952911
TI  - Vascularised iliac bone grafting in the treatment of femoral neck nonunion in
      young adults: a retrospective study.
AB  - INTRODUCTION: Revision internal fixation for femoral neck nonunion in young
      patients can pose a surgical challenge. Hip salvage protocols include osteotomy
      and osteosynthesis using various implants and grafting techniques (muscle
      pedicle, vascularised or nonvascularised fibular graft). The purpose of this
      study was to evaluate the clinical outcomes of vascularised iliac grafting for
      femoral neck nonunion in patients younger than 50 years. MATERIALS AND METHODS: A
      total of 22 patients underwent vascularised iliac grafting and internal fixations
      for femoral neck nonunion were retrospectively analysed. Their mean age was 36.6
      years. The cases were evaluated radiographically and clinically. RESULTS: All the
      patients were followed-up for an average of 64.6 months. The mean time to union
      for all patients was 5.4 months. The mean Harris Hip Score had increased from
      55.3 preoperatively to 85.2 at the latest follow-up. The average neck-shaft angle
      had changed from 127.4 degrees  preoperatively to 128.3 degrees  postoperatively.
      Postoperative progression of osteonecrosis of the femoral head was seen in 3
      patients, 2 patients were pain free and 1 patient required total hip arthroplasty
      9 years after the revision procedure. There was no further progression in 3
      patients with preoperative radiological evidence of the femoral head
      osteonecrosis. CONCLUSIONS: This study indicates that vascularised iliac grafting
      is a viable option in treatment of femoral neck nonunion in the young adult.

PMID- 25952912
TI  - High early migration of the revised acetabular component is a predictor of late
      cup loosening: 312 cup revisions followed with radiostereometric analysis for 2
      20 years.
AB  - INTRODUCTION: Radiostereometric analysis (RSA) is an accurate and precise
      measurement tool of migration and rotation of implants. We investigated if early
      migration measured with RSA can be used to predict the risk of later aseptic
      loosening in acetabular revision surgery. PATIENTS AND METHODS: A total of 312
      patients who underwent acetabular revision surgery were followed by RSA
      measurements for 2 to 20 years. The endpoint was either re-revision due to
      aseptic loosening or loosening on last available radiographic examination. Cox
      regression model was used to evaluate the predictive value of early migration.
      RESULTS: A total of 16 acetabular cups were re-revised due to aseptic loosening
      and 7 unrevised cups were radiographically loose. Every mm of proximal migration
      2 years postoperatively increased the risk of aseptic loosening by 37% (hazard
      ratio (HR) 1.37, 95% confidence interval (CI) 1.18-1.58). Adjusting for
      differences in base line demographics, bone defects and surgical techniques in a
      Cox regression model, risk of aseptic loosening with every mm of proximal
      migration was even higher (HR 1.94, 95% CI 1.34-2.82, p<0.001). CONCLUSIONS: We
      found a strong relationship between early migration measured by RSA and risk of
      late aseptic loosening in acetabular revision surgery. Monitoring proximal
      migration with RSA should be considered as an essential step in quality
      assessment when new implants and novel techniques are introduced in acetabular
      revision surgery.

PMID- 25952913
TI  - Aseptic loosening of cobalt chromium monoblock sockets after hip resurfacing.
AB  - INTRODUCTION: Acetabular component loosening is a leading cause for revision
      after metal-on-metal hip resurfacing arthroplasty (MMHRA). We aimed to identify
      potential risk factors and determine radiographic signs associated with this mode
      of failure. METHODS: From a series of 1375 hips treated with MMHRA, 21 (20
      patients) underwent revision surgery secondary to aseptic loosening of the
      acetabular component and 6 patients had a radiographically loose acetabular
      component. A control group of 27 hips (26 patients) was selected among the
      patients that did not have a revision, and was matched for age, gender, component
      size and diagnosis. RESULTS: Mean time to revision in the loosening group was
      103.0 months and the mean time of follow-up in the control group was 161.4
      months. We found greater activity levels, range of motion scores, and cup
      abduction angles in the loosening group. The centre-edge (CE) angle of Wiberg was
      10 degrees  lower in the loosening group compared with the control group. In
      addition, 11 of the hips from the study group presented a sclerotic halo superior
      to the cup on the last radiograph vs. none in the control group. There was no
      difference in the prevalence of postoperative reaming gaps or radiographic signs
      of neck-cup impingement between the 2 groups. DISCUSSION: Risk factors for
      acetabular loosening included hip dysplasia with low CE angle, and a large cup
      abduction angle. The patient's level of activity influences the appearance of
      symptoms and the time to revision. We recommend selecting patients with a
      sufficient CE angle and properly orienting the cup.

PMID- 25952914
TI  - Detailed inspection of metal implants.
AB  - Detailed visual inspection of metal hips is the first step in retrieval analysis.
      In this study a systematic visual inspection protocol was developed to quantify
      bearing surface changes and their associations with material loss was
      investigated. Simple and multiple linear regression models found that moderate
      surface scratching, discolouration, haziness and the size of visible wear scars
      were all significantly associated with material loss (R2 = 5%-73%, p<0.05).
      Visual inspection is not a substitute for measurement of material loss but an
      understanding of bearing surface changes may offer unique clues as to the
      mechanisms of failure of retrieved hips. 

PMID- 25952915
TI  - Survival, clinical and radiological outcome of the Zweymuller SL/Bicon-Plus total
      hip arthroplasty: a 15-year follow-up study.
AB  - AIM: The primary aim of this study is to analyse the long-term results of the
      third generation of the "Zweymuller" total hip arthroplasty (THA) comprising the
      SL-Plus Stem and the Bicon-Plus cup. METHODS: We evaluated 208 patients with a
      SL/Bicon-Plus primary THA (218 hips). Survival analysis was performed with a
      follow-up of 13 to 15 years. Complementary clinical and radiological analysis was
      performed using the "Hip Injury and Osteoarthritis Outcome Score" (HOOS) and x
      rays of the hips. RESULTS: The probability of survival of the stem and cup with
      revision for any reason was respectively 0.96/0.97 at 10 years and 0.92/0.94 at
      15 years. The probability of survival of the stem and cup with revision for
      aseptic loosening was respectively 0.99/0.97 at 10 years and 0.95/0.94 at 15
      years. Clinical assessment of the patients, reported by the HOOS, were scored
      with a median for the subdivisions: symptoms 90%, pain 93%, function in daily
      activity 87%, function in leisure or sport 75%, and quality of life with 75%.
      Periprosthetic radiolucent lines were observed in half of all hips in Gruen zones
      1 and 7. Mean linear wear of the polyethylene was 1.8 mm which corresponds to
      0.12 mm/year. 2/3 of the hips show heterotopic ossifications, mostly Brooker type
      1 and 2. CONCLUSIONS: The "third generation" Zweymuller total hip arthroplasty
      consisting of the SL stem and the Bicon cup has good long term results in terms
      of survival, clinical and radiological outcome.

PMID- 25952916
TI  - Long-term result of mosaicplasty for femoral head osteochondral lesion: a case
      report with 8 years follow-up.
AB  - PURPOSE: Treatment of the chondral lesions of the hip joint is problematic due to
      its deep anatomy and complex biomechanical demands. The purpose of the study is
      to present the long-term result of a deep, large femoral head cartilage defect
      treated successfully with surgical safe dislocation of the hip and autologous
      osteochondral grafting. METHODS: A 27-year-old male patient was admitted to our
      clinic with left hip pain. On assessment, a large femoral head osteochondral
      defect was detected in his left hip. An open safe hip dislocation and autologous
      osteochondral grafting was performed due to the large size of the lesion and
      subchondral bone involvement. RESULTS: Using a Kocher-Langenbeck incision, the
      hip was dislocated after a trochanteric flip osteotomy. The defect was
      reconstructed with 3 x 13 mm and 1 x 11 mm osteochondral plug from the
      ipsilateral knee. We have not encountered any complication at the postoperative
      period. After 8 years follow-up his left hip range of motion was preserved and
      The Harris Hip Score was qualified as excellent with 96 points. CONCLUSIONS:
      Chondral defects of the femoral head are still a challenging problem in
      orthopaedic practice. Mosaicplasty of the femoral head is a demanding procedure
      with safe dislocation of the hip. However, if successful it can provide
      satisfactory functional and radiological results in the long-term.

PMID- 25952918
TI  - The anatomy and function of the obturator externus.
AB  - There is limited knowledge regarding the anatomic relationships and functional
      anatomy of the Obturator Externus muscle (OE). It is described as a muscle which
      originates from the external bony margin of the obturator foramen with a
      cylindrical tendon which passes like a sling under the femoral neck and inserts
      in the trochanteric fossa. The primary aim of this study is to describe the OE
      morphology and its anatomic relationship to the acetabulum. A secondary aim is to
      postulate its action. Eighteen fresh human cadaveric hips were dissected to
      investigate the anatomy of the OE. A plastic model of the pelvis and femur was
      used to create a string model based on a technique previously described by Beck
      et al. The plastic model was used to determine the function of the OE.We conclude
      that the Obturator externus muscle helps to stabilise the head of the femur in
      the socket. The mechanical model demonstrated that the primary action of the
      obturator externus muscle was to externally rotate the femur when the hip was in
      neutral position and flexed at 90 degrees . Its secondary function was as an
      adductor when the hip was in flexion. 

PMID- 25952917
TI  - The analysis of posterior soft tissue repair durability after total hip
      arthroplasty in primary osteoarthritis patients.
AB  - BACKGROUND AND PURPOSE: The posterior soft tissue repair is 1 of the preventing
      factors for dislocation after total hip arthroplasty (THA).The aim of our study
      was to analyse THA patients with posterior soft tissue repair in terms of suture
      durability, time of suture failure and correlate the changes in leg length and
      offset postoperatively to suture durability. METHODS: A total of 37 consecutive
      THA patients operated for osteoarthritis were included in the study. The
      posterior repair included reattaching the piriformis, conjoined tendons and
      posterior capsule to the greater trochanter through 2, 2 mm drill holes with 2
      grasping stitches. A metal indicator wire was stitched into the piriformis tendon
      at distance of 1 cm from the greater trochanter after the prosthesis had been
      implanted and the joint reduced. Anteroposterior radiographs were taken
      immediately after the patients returned from the operating theatre to the
      intensive care unit, the next day after mobilisation, and at the 5th day of stay
      and at 3 months postoperatively. RESULTS: Out of 37 THA hips, 6 (16%) had failed
      immediately after surgery, 25 (68%) at the 1st postoperative day after
      mobilisation, 2 (5%) at the 5th postoperative day, and 1 (3%) repairs had failed
      at 3 months after THA. In the remaining 3 hips no failure occurred.
      INTERPRETATION: We conclude that posterior soft tissue repair in THA often fails
      and suggest that new posterior soft tissue repair methods be developed.

PMID- 25952919
TI  - Treatment of massive acetabular bone loss and pelvic discontinuity with a custom
      triflange component and ilio-sacral fixation based on preoperative CT templating.
      A report of 2 cases.
AB  - Revision rates for total hip arthroplasty are increasing and pelvic discontinuity
      is estimated to be present in 1% to 5% (Berry). Discontinuity is defined as a
      separation of the cephalad portion of the pelvis from the caudad portion (AAOS
      Type IV defects). This results from bone loss secondary to osteolysis, infection,
      fracture, or mechanical loosening. The goals of revision surgery in this setting
      are to obtain secure fixation of the acetabular component with or without union
      of the discontinuity. Many methods exist for treating this problem. Results with
      allograft and cage fixation have generally been poor (Berry, Hansen). More
      favourable outcomes have been reported using either a cup cage technique or
      custom triflange (Gross, Christie). The custom Triflange component is designed
      based on preoperative imaging with CT scan to manufacture a custom titanium
      implant to address the patient's specific bone loss pattern and obtain secure
      fixation in the ilium, pubis, and ischium. However, we have encountered cases of
      acetabular discontinuity with massive pelvic bone loss in which bone stock in the
      ilium was insufficient to provide support for proximal fixation of a conventional
      custom triflange component. Currently in the trauma patient population posterior
      pelvic ring disruptions are being treated with ilio-sacral screw fixation. The
      sacrum provides a source of secure bony fixation for these injuries. We report on
      2 patients with pelvic discontinuity and massive bone loss using a technique to
      obtain proximal fixation of a custom triflange component into the sacrum.

PMID- 25952920
TI  - The prevalence of femoroacetabular impingement in radiographs of asymptomatic
      subjects: a cross-sectional study.
AB  - BACKGROUND: There is a lack of uniformity in the diagnostic criteria for
      femoroacetabular impingement (FAI), and few studies discuss the prevalence of
      radiographic changes in asymptomatic individuals. These factors make it difficult
      to establish a natural history of this disease. The aim of this study was to
      assess the prevalence of radiographic signs of CAM and Pincer FAI in an
      asymptomatic population. METHODS: A cross-sectional study was performed from July
      2013 to December 2013. A total of 185 subjects were analysed. INCLUSION CRITERIA:
      no history of hip pain or orthopedic disease; and being 20-60 years old.
      EXCLUSION CRITERIA: athletically active; or patients who would not allow
      acquisition of appropriate radiographs for analysis. Radiographs were obtained in
      anteroposterior and Dunn 45 degrees  view to access: alpha angle (AA), triangular
      index (TI), crossover sign (CS), lateral-centre edge (LCE) angle and acetabular
      index (AI). RESULTS: Median age was 34 years (27-49.5) and FAI was present in 53%
      of all subjects. 32.44% (60) was the overall CAM-type prevalence and 42.7% (79)
      the overall Pincer-type prevalence. Only 2 subjects presented the 3 overcoverage
      signs (AI, LCE and CS). An association was noted between the presence of AI <0
      degrees  and the LCE >40 degrees  (p = 0.05). CONCLUSIONS: Our study established
      a higher prevalence of radiographic markers of FAI in an asymptomatic population.

PMID- 25952921
TI  - Osteoclastogenesis-related cytokines and peri-prosthetic osteolysis in revision
      metal-on-metal total hip replacements.
AB  - PURPOSE: Peri-prosthetic osteolysis is a major cause for revision hip
      arthroplasty; various cytokines including those in the osteoclastogenesis pathway
      have been identified as potentially key in the osteolysis process. Adverse
      reactions to metal debris in metal-on-metal total hip replacements have led to an
      increase in revision procedures. This study examines the levels of
      osteoclastogenesis-related cytokines in serum and synovial fluid samples obtained
      from patients at the time of revision metal-on-metal total hip replacement and
      compares between patients with and without radiographic evidence of peri
      prosthetic osteolysis. METHODS: Sandwich ELISA techniques were used to detect IL
      6, IL-18, M-CSF, sRANKL and OPG in the samples. Results were analysed with linear
      regression, Fisher's tests and t-tests; p<0.05 considered significant. Samples
      from 36 patients (18 with osteolysis, 18 without osteolysis) were analysed.
      RESULTS: There was wide variation in the detectable levels of cytokines. No
      significant differences were found between patients with and without osteolysis
      in mean synovial fluid levels of IL-6 (p = 0.863), IL-18 (p = 0.324), M-CSF (p =
      0.508), sRANKL (p = 0.884), OPG (p = 0.776) or mean serum levels of OPG (p =
      0.993) or sRANKL (p = 0.565) (insufficient detection of IL-6, IL-18 or M-CSF in
      serum samples). A correlation was found between synovial fluid levels of IL-6 and
      OPG in patients without osteolysis (r2 = 0.618, p<0.001) but not with osteolysis
      (r2 = 0.0004). CONCLUSIONS: These results indicate that the process of peri
      prosthetic osteolysis is complex and multifactorial; there may also be an
      influence of metallosis. Further research is needed to increase understanding of
      peri-prosthetic osteolysis and influence clinical practice.

PMID- 25952922
TI  - Low wear, high stability - promises of success in a moderately cross-linked cup?
AB  - PURPOSE: Cross-linking has proven effective in reducing polyethylene wear in
      total hip replacements. However, increasing the amount of cross-links will impair
      other mechanical properties of the polyethylene. The optimal threshold of
      crosslinking has still not been established. This led to the development of a
      moderately cross-linked (5 Mrad) cemented cup in which wear and stability is yet
      to be determined. METHODS: A total of, 70 hips were included in this case series
      on the cemented Marathon(r) cup. Mean age of the patients was 78 years (SD 15).
      We measured wear and migration by radiostereometry at 3, 12 and 24 months.
      RESULTS: The proximal wear rate estimate between 3 to 24 months was 0.036
      mm/year, and a total proximal wear estimate at 2 years of 0.11 mm (95% CI 0.09
      0.14). Translations and rotations along the 3 cardinal axes were all at or below
      the precision limit, and less than what is believed to be predictive of later
      loosening, namely 0.2-1 mm for proximal migration. The cups remained stable after
      the initial "bedding in" that occurred during the first 3 months. CONCLUSIONS:
      Our results indicate that moderate cross-linking (5Mrad) yields low wear and high
      stability in this specific acetabular cup, comparable to other cups with higher
      cross-linking.

PMID- 25952923
TI  - Anemia and hemoglobin serum levels are associated with exercise capacity and
      quality of life in chronic obstructive pulmonary disease.
AB  - BACKGROUND: Little is known about the relationship between hemoglobin
      concentrations, functional status and health related quality of life (HRQL) in
      chronic obstructive pulmonary disease (COPD). Our aim was to investigate the
      prevalence of anemia and the association of hemoglobin with shortness of breath,
      exercise capacity, muscle strength and HRQL, in COPD patients. METHODS: A total
      of 105 COPD patients (77 males, 71.6 +/- 9.2 years) were studied. Patients were
      classified as anemic and non anemic using the WHO criteria. We used the Medical
      Research Council Dyspnoea scale (MRCs) to measure shortness of breath. Exercise
      capacity was assessed using the six minute walking distance (6MWD) and the peak
      of VO2 during the maximal cycle ergometer test (VO2max). We used the Quadriceps
      and Handgrip strength assessment to determine muscle strength. The Saint George
      Respiratory Questionnaire was used to investigate HRQL. The
      physiological/functional characteristics of the two groups were compared.
      Regression models adjusting for confounders examined the independent association
      of anemia and of hemoglobin levels with clinical and functional outcomes.
      RESULTS: Anemic patients (12.3%) showed a significantly higher MRCs, a lower
      6MWD, VO2max, and a worse quality of life. On the contrary, there was no
      difference in muscle strength between the two groups. In the regression models,
      hemoglobin was independently associated with reduced exercise capacity and HRQL.
      CONCLUSIONS: Anemia in COPD was a risk factor for poorer exercise capacity and
      quality of life, and these outcomes were linearly associated with hemoglobin. Our
      results should stimulate further research into exploring whether increasing
      hemoglobin has a beneficial effect on the outcomes in COPD.

PMID- 25952925
TI  - Patient-based outcomes following surgical implant placements.
AB  - OBJECTIVES: To assess the postoperative oral health-related quality of life
      (OHRQoL), pain and swelling after surgical implant placement and to investigate
      their association with socio-demographic and clinical variables. MATERIALS AND
      METHODS: A total of 85 partial edentulous patients requiring implant-supported
      fixed prostheses were enrolled. Standard surgical practice for implant placement
      was employed. Interviews were conducted to assess the OHRQoL based on the oral
      impact on daily performances (OIDP) index preoperatively as well as 2 weeks and 1
      month postoperatively in addition to the degree of pain and swelling at 2 weeks
      postoperatively. The socio-demographic and clinical variables of interest were
      also assessed. RESULTS: Patient's OHRQoL was reduced at 2 weeks followed by a
      return to baseline levels 1 month postoperatively. The median OIDP scores were
      5.0, 12.0 and 3.5 preoperatively, 2 weeks and 1 month postoperatively,
      respectively. Eating and teeth cleaning were affected after surgery. Overall,
      50.6% of the patients perceived no to mild pain, whereas 36.5%, 49.4% and 14.1%
      reported no, localized or extensive facial swelling, respectively. No association
      was found between pain and any variable, but anterior implantation and bone
      augmentation were more commonly associated with facial swelling. Oral health
      related quality of life worsened in patients with more pain or facial swelling as
      well as in cases involving multiple implant placement or bone augmentation
      procedures. CONCLUSIONS: Oral health-related quality of life deteriorated shortly
      after surgery based on eating and teeth cleaning difficulties. A high degree of
      pain, extensive swelling, multiple implant placement and bone augmentation
      procedures were all associated with oral impacts.

PMID- 25952924
TI  - DNA methylation analysis of phenotype specific stratified Indian population.
AB  - BACKGROUND: DNA methylation and its perturbations are an established attribute to
      a wide spectrum of phenotypic variations and disease conditions. Indian
      traditional system practices personalized medicine through indigenous concept of
      distinctly descriptive physiological, psychological and anatomical features known
      as prakriti. Here we attempted to establish DNA methylation differences in these
      three prakriti phenotypes. METHODS: Following structured and objective
      measurement of 3416 subjects, whole blood DNA of 147 healthy male individuals
      belonging to defined prakriti (Vata, Pitta and Kapha) between the age group of 20
      30years were subjected to methylated DNA immunoprecipitation (MeDIP) and
      microarray analysis. After data analysis, prakriti specific signatures were
      validated through bisulfite DNA sequencing. RESULTS: Differentially methylated
      regions in CpG islands and shores were significantly enriched in promoters/UTRs
      and gene body regions. Phenotypes characterized by higher metabolism (Pitta
      prakriti) in individuals showed distinct promoter (34) and gene body methylation
      (204), followed by Vata prakriti which correlates to motion showed DNA
      methylation in 52 promoters and 139 CpG islands and finally individuals with
      structural attributes (Kapha prakriti) with 23 and 19 promoters and CpG islands
      respectively. Bisulfite DNA sequencing of prakriti specific multiple CpG sites in
      promoters and 5'-UTR such as; LHX1 (Vata prakriti), SOX11 (Pitta prakriti) and
      CDH22 (Kapha prakriti) were validated. Kapha prakriti specific CDH22 5'-UTR CpG
      methylation was also found to be associated with higher body mass index (BMI).
      CONCLUSION: Differential DNA methylation signatures in three distinct prakriti
      phenotypes demonstrate the epigenetic basis of Indian traditional human
      classification which may have relevance to personalized medicine.

PMID- 25952926
TI  - Burden in caregivers of long-term stroke survivors: Prevalence and determinants
      at 6 months and 5 years after stroke.
AB  - OBJECTIVES: To assess the prevalence of considerable burden among caregivers of
      stroke survivors at 6 months (Time 1) and 5 years after stroke (Time 2), to
      analyse changes in burden severity over time and to identify factors associated
      with the burden. METHODS: Eighty eight patient/caregiver pairs were assessed.
      Caregiver burden was measured with the Caregiver Burden Scale. Socio-demographic,
      stroke-related and psychological characteristics were analysed as potential
      determinants of the burden. Exact multiple logistic regression was used to
      identify the predictive factors. RESULTS: Considerable burden was reported by 44%
      of the caregivers at Time 1 and 30% at Time 2. The burden was independently
      associated with caregivers' sense of coherence and amount of time spent
      caregiving at Time 1, and with caregivers' anxiety at Time 2. CONCLUSIONS: A
      significant proportion of the caregivers experienced considerable burden in the
      post-acute and chronic phases of stroke, although this proportion declined over
      time. Several characteristics were associated with the increased burden at
      different time points. All the independent predictors related to aspects of the
      carers. PRACTICE IMPLICATIONS: Programmes including education about coping
      strategies and time management, as well as respite care provision, could be
      beneficial and might help to reduce the burden of caregiving.

PMID- 25952927
TI  - Attitudes of Portuguese medical residents' towards clinical communication skills.
AB  - OBJECTIVE: To explore the attitudes and perceptions of Portuguese residents
      towards Clinical Communication Skills (CCS) and the need for complementary
      training. METHODS: 78 medical residents responded to an on-line questionnaire
      which comprised demographic data, open-ended questions and a Portuguese version
      of the Communication Skills Attitude Scale (CSAS). RESULTS: Residents gave
      significantly higher scores (P<0.001) on CSAS1 (attitudes towards communication
      skills in general, compared to CSAS2 (attitudes towards the teaching/learning
      process of CCS). Residents doing their residency training in other parts of the
      country, other than the north, reveal a higher perception of insufficient
      training (72.7% vs. 38.7%, P=0.036). CONCLUSION: Residents showed more positive
      attitudes towards communication skills than towards the teaching/learning
      process. They admit to need more training in CCS in their residency year and
      highlight that the clinical cycle of undergraduate education should integrate
      these topics. Content analysis indicates that residents' perceptions are context
      influenced. PRACTICE IMPLICATIONS: Integration of CCS in the undergraduate
      education, enhanced during post-graduate training. Training of clinical faculty
      and supervisors/tutors and the role that stakeholders have to play in order to
      promote continuous training in CCS; encourage patient-centeredness and reflective
      practice, as to facilitate transfer of acquired skills to clinical practice.

PMID- 25952928
TI  - LncRNA HULC affects the differentiation of Treg in HBV-related liver cirrhosis.
AB  - BACKGROUND AND AIMS: Recently, a couple of the long noncoding RNAs (lncRNAs) have
      been proved to participate in hepatocellular carcinoma development and
      progression. However, their associations with liver cirrhosis have not been
      reported. In this study, we aimed to identify the affection of HULC on regulatory
      T cells (Tregs) differentiation in HBV-related liver cirrhosis. METHODS: Seven
      lncRNAs were chosen as candidate lncRNAs based on the association with liver
      disease. The candidate lncRNAs were validated by RT-qPCR. Additional flow
      cytometry of Tregs was performed in 34 HBV-related liver cirrhosis patients and
      34 healthy volunteers. To investigate the function of HULC, HULC expression was
      modified by gene overexpression via lentivirus vector. RIP assay was performed
      further to validate the association between HULC and p18. RESULTS: Circulation
      Tregs and HULC were significantly up-regulated in plasma samples of HBV-related
      cirrhosis patients. In addition, overexpression of HULC by lentivirus vector
      elevated Treg frequency in vitro. Furthermore, RIP assay showed that HULC down
      regulated the level of p18 directly. CONCLUSIONS: We confirmed the effects of
      HULC on Tregs differentiation in HBV-related liver cirrhosis. In addition, it was
      proved that HULC regulates the function of Tregs through down-regulated the level
      of p18 directly.

PMID- 25952929
TI  - Testate amoeba Rhogostoma minus Belar, 1921, associated with nodular gill disease
      of rainbow trout, Oncorhynchus mykiss (Walbaum).
AB  - The case study targeted to determine the aetiology of nodular gill disease (NGD)
      of farmed rainbow trout. The methods included microscopical examination of gill
      material in fresh, culturing of isolated organisms, histology, transmission
      electron microscopy and molecular biology identification. The results revealed an
      intravital colonization of fish gills by the testate amoeba Rhogostoma minus
      Belar, 1921. Rhogostoma infection was found in all fish examined microscopically
      (15/15); in contrast, naked amoebae related to fully developed NGD lesions were
      found in minority of these fish (5/15). They belonged to four genera,
      Acanthamoeba, Vermamoeba, Naegleria and Vannella. Results presented in this study
      contribute to the mosaic of findings that contrary to amoebic gill disease of
      marine fish turn attention to the possibility of the heterogeneous, multi-amoeba
      species and multifactorial aetiology of NGD. 

PMID- 25952931
TI  - Caring for quality of care: symbolic violence and the bureaucracies of audit.
AB  - BACKGROUND: This article considers the moral notion of care in the context of
      Quality of Care discourses. Whilst care has clear normative implications for the
      delivery of health care it is less clear how Quality of Care, something that is
      centrally involved in the governance of UK health care, relates to practice.
      DISCUSSION: This paper presents a social and ethical analysis of Quality of Care
      in the light of the moral notion of care and Bourdieu's conception of symbolic
      violence. We argue that Quality of Care bureaucracies show significant potential
      for symbolic violence or the domination of practice and health care
      professionals. This generates problematic, and unintended, consequences that can
      displace the goals of practice. SUMMARY: Quality of Care bureaucracies may have
      unintended consequences for the practice of health care. Consistent with feminist
      conceptions of care, Quality of Care 'audits' should be reconfigured so as to
      offer a more nuanced and responsive form of evaluation.

PMID- 25952930
TI  - The combination of sorafenib and everolimus shows antitumor activity in
      preclinical models of malignant pleural mesothelioma.
AB  - BACKGROUND: Malignant Pleural Mesothelioma (MPM) is an aggressive tumor arising
      from mesothelial cells lining the pleural cavities characterized by resistance to
      standard therapies. Most of the molecular steps responsible for pleural
      transformation remain unclear; however, several growth factor signaling cascades
      are known to be altered during MPM onset and progression. Transducers of these
      pathways, such as PIK3CA-mTOR-AKT, MAPK, and ezrin/radixin/moesin (ERM) could
      therefore be exploited as possible targets for pharmacological intervention. This
      study aimed to identify 'druggable' pathways in MPM and to formulate a targeted
      approach based on the use of commercially available molecules, such as the
      multikinase inhibitor sorafenib and the mTOR inhibitor everolimus. METHODS: We
      planned a triple approach based on: i) analysis of immunophenotypes and
      mutational profiles in a cohort of thoracoscopic MPM samples, ii) in vitro
      pharmacological assays, ii) in vivo therapeutic approaches on MPM xenografts. No
      mutations were found in 'hot spot' regions of the mTOR upstream genes (e.g. EGFR,
      KRAS and PIK3CA). RESULTS: Phosphorylated mTOR and ERM were specifically
      overexpressed in the analyzed MPM samples. Sorafenib and everolimus combination
      was effective in mTOR and ERM blockade; exerted synergistic effects on the
      inhibition of MPM cell proliferation; triggered ROS production and consequent
      AMPK-p38 mediated-apoptosis. The antitumor activity was displayed when orally
      administered to MPM-bearing NOD/SCID mice. CONCLUSIONS: ERM and mTOR pathways are
      activated in MPM and 'druggable' by a combination of sorafenib and everolimus.
      Combination therapy is a promising therapeutic strategy against MPM.

PMID- 25952932
TI  - Midwives as primary care providers for women.
AB  - Midwives certified by the American Midwifery Certification Board (AMCB) are
      prepared to provide primary care to women from menarche across the lifespan and
      to well newborns to 28 days using consultation, collaboration, and referral to
      other providers as needed. The scope of midwifery in the United States did not
      always include primary care for women, although imprecise definitions of primary
      care make this difficult to study. The expansion of the scope of practice
      occurred in response to population needs and research on nurse-midwifery practice
      patterns. The scope of practice of midwifery is tied to educational standards
      through the regulation and licensure at the state level. Although the current
      scope of practice includes primary care for women, many certified nurse-midwives
      and certified midwives are unable to practice to the full extent of their
      education due to state-level licensure restrictions. We discuss the addition of
      primary care to midwifery and the current state of AMCB-certified midwives as
      primary care providers for women. 

PMID- 25952933
TI  - Maxillary sinusitis diagnosed by ultrasound.

PMID- 25952934
TI  - Relationship between insulin resistance and amino acids in women and men.
AB  - Insulin resistance has been associated with higher plasma amino acid (AA)
      concentrations, but majority of studies have used indirect measures of insulin
      resistance. Our main objective was to define the relationship between plasma AA
      concentrations and a direct measure of insulin resistance in women and men. This
      was a cross-sectional study of 182 nondiabetic individuals (118 women and 64 men)
      who had measurement of 24 AAs and steady-state plasma glucose (SSPG)
      concentration (insulin resistance) using the insulin suppression test. Fourteen
      out of 24 AA concentrations were significantly (P < 0.05) higher in men than
      women; only glycine was lower in men. Majority of these AAs were positively
      associated with SSPG; only glycine concentration was negatively associated.
      Glutamic acid, isoleucine, leucine, and tyrosine concentrations had the strongest
      correlation with SSPG (r >= 0.4, P < 0.001). The degree of association was
      similar in women and men, independent of obesity, and similar to traditional
      markers of insulin resistance (e.g., glucose, triglyceride, high-density
      lipoprotein cholesterol). Compared with women, men tended to have a more
      unfavorable AA profile with higher concentration of AAs associated with insulin
      resistance and less glycine. However, the strength of association between a
      direct measurement of insulin resistance and AA concentrations were similar
      between sexes and equivalent to several traditional markers of insulin
      resistance. 

PMID- 25952935
TI  - Impact of anesthesia and storage on posttranslational modifications of cardiac
      myofilament proteins.
AB  - Although high fidelity measurements of posttranslational modifications (PTMs) of
      cardiac myofilament proteins exist, important issues remain regarding basic
      techniques of sample acquisition and storage. We investigated the effects of
      anesthetic regimen and sample storage conditions on PTMs of major ventricular
      sarcomeric proteins. Mice were anesthetized with pentobarbital (Nembutal),
      ketamine/xylazine mixture (Ket/Xyl), or tribromoethanol (Avertin), and the
      ventricular tissue was prepared and stored for 1, 7, 30, 60, or 90 days at -80
      degrees C. Myofilament protein phosphorylation and glutathionylation were
      analyzed by Pro-Q Diamond stain and Western blotting, respectively. With up to 7
      days of storage, phosphorylation of troponin T was stable for samples from mice
      anesthetized with either Nembutal or Ket/Xyl but not Avertin; while myosin
      binding protein C (MyBP-C) phosphorylation was reduced at 7 days with Nembutal
      and Ket/Xyl, though generally not significant until 90 days. Tropomyosin and
      regulatory myosin light chain phosphorylation were stable for up to 7 days
      regardless of the anesthetic regimen employed. In the case of Troponin I, by 7
      days of storage there was a significant fall in phosphorylation across all
      anesthetics. Storage of samples from 30 to 90 days resulted in a general decrease
      in myofilament phosphorylation independent of the anesthetic. S-glutathionylation
      of MyBP-C presented a trend in reduced glutathionylation from days 30-90 in all
      anesthetics, with only day 90 being statistically significant. Our findings
      suggest that there are alterations in PTMs of major myofilament proteins from
      both storage and anesthetic selection, and that storage beyond 30 days will
      likely result in distortion of data. 

PMID- 25952936
TI  - Ischemic preconditioning accelerates muscle deoxygenation dynamics and enhances
      exercise endurance during the work-to-work test.
AB  - Ischemic preconditioning (IPC) improves maximal exercise performance. However,
      the potential mechanism(s) underlying the beneficial effects of IPC remain
      unknown. The dynamics of pulmonary oxygen uptake (VO2) and muscle deoxygenation
      during exercise is frequently used for assessing O2 supply and extraction. Thus,
      this study examined the effects of IPC on systemic and local O2 dynamics during
      the incremental step transitions from low- to moderate- and from moderate- to
      severe-intensity exercise. Fifteen healthy, male subjects were instructed to
      perform the work-to-work cycling exercise test, which was preceded by the control
      (no occlusion) or IPC (3 * 5 min, bilateral leg occlusion at >300 mmHg)
      treatments. The work-to-work test was performed by gradually increasing the
      exercise intensity as follows: low intensity at 30 W for 3 min, moderate
      intensity at 90% of the gas exchange threshold (GET) for 4 min, and severe
      intensity at 70% of the difference between the GET and VO2 peak until exhaustion.
      During the exercise test, the breath-by-breath pulmonary VO2 and near-infrared
      spectroscopy-derived muscle deoxygenation were continuously recorded. Exercise
      endurance during severe-intensity exercise was significantly enhanced by IPC.
      There were no significant differences in pulmonary VO2 dynamics between
      treatments. In contrast, muscle deoxygenation dynamics in the step transition
      from low- to moderate-intensity was significantly faster in IPC than in CON (27.2
      +/- 2.9 vs. 19.8 +/- 0.9 sec, P < 0.05). The present findings showed that IPC
      accelerated muscle deoxygenation dynamics in moderate-intensity exercise and
      enhanced severe-intensity exercise endurance during work-to-work test. The IPC
      induced effects may result from mitochondrial activation in skeletal muscle, as
      indicated by the accelerated O2 extraction. 

PMID- 25952937
TI  - Depression and anxiety in chronic rhinosinusitis.
AB  - BACKGROUND: Both depression and anxiety have been suspected to impact quality of
      life adversely in patients with chronic rhinosinusitis (CRS). The objective of
      this work was to assess for the presence of anxiety and/or depression in the
      setting of CRS and to assess their impact on disease-related quality of life by
      analyzing the correlation between the Rhinosinusitis Disability Index (RSDI) and
      the Hospital Anxiety and Depression score (HADS), as well as the Lund-Kennedy
      nasal endoscopic scores. METHODS: A total of 124 patients with CRS were
      prospectively evaluated in the outpatient setting using the RSDI and HADS
      questionnaires as well as the Lund-Kennedy nasal endoscopy scoring system.
      RESULTS: The total RSDI and its subscale scores had moderate to very strong
      correlation with the HADS total score and each of its subscale scores in
      comparison to their poor correlation with Lund-Kennedy endoscopic score. CRS
      patients with depression or anxiety scores 8 to 10 (possible case of clinically
      significant depression or anxiety) and 11 to 21 (probable case) reported worse
      total RSDI and subscale scores when compared with those with normal scores (0 to
      7). There was no significant difference in the Lund-Kennedy endoscopic scores
      between the different groups of anxiety and depression scores. CONCLUSION:
      Depression and anxiety are prevalent in CRS. The total RSDI and its different
      subscale scores exhibit moderate to very strong correlation with
      depression/anxiety scores as determined by HADS, whereas poor correlation was
      seen with the Lund-Kennedy endoscopic score.

PMID- 25952938
TI  - A novel procedure for statistical inference and verification of gene regulatory
      subnetwork.
AB  - BACKGROUND: The reconstruction of gene regulatory network from time course
      microarray data can help us comprehensively understand the biological system and
      discover the pathogenesis of cancer and other diseases. But how to correctly and
      efficiently decifer the gene regulatory network from high-throughput gene
      expression data is a big challenge due to the relatively small amount of
      observations and curse of dimensionality. Computational biologists have developed
      many statistical inference and machine learning algorithms to analyze the
      microarray data. In the previous studies, the correctness of an inferred
      regulatory network is manually checked through comparing with public database or
      an existing model. RESULTS: In this work, we present a novel procedure to
      automatically infer and verify gene regulatory networks from time series
      expression data. The dynamic Bayesian network, a statistical inference algorithm,
      is at first implemented to infer an optimal network from time series microarray
      data of S. cerevisiae, then, a weighted symbolic model checker is applied to
      automatically verify or falsify the inferred network through checking some
      desired temporal logic formulas abstracted from experiments or public database.
      CONCLUSIONS: Our studies show that the marriage of statistical inference
      algorithm with model checking technique provides a more efficient way to
      automatically infer and verify the gene regulatory network from time series
      expression data than previous studies.

PMID- 25952939
TI  - Understanding the Stress Management Needs and Preferences of Latinas Undergoing
      Chemotherapy.
AB  - This exploratory study provides insights into everyday realities, concerns, and
      cultural perspectives of Latinas undergoing chemotherapy, and elicits information
      on stress management and information needs. Informed by a community-based
      participatory research approach using qualitative methods, we conducted ten
      interviews with providers, and two focus groups (n = 13) and 20 in-depth
      interviews with Latinas recently diagnosed with breast cancer. Providers and
      Latina patients acknowledged multiple physical and emotional stressors associated
      with cancer treatment, viewed a positive aspect of the cancer experience to
      include connection with God and enhanced spirituality, saw family as a motivating
      factor for recovery, and expressed a need to draw on existing coping strategies.
      Findings show considerable overlap between providers and Latina cancer patients'
      perceptions of stressors during chemotherapy. However, a few notable differences
      in perceptions of stress management needs during this treatment period emerged.
      While Latina cancer patients mentioned similar social/structural stressors (e.g.,
      economic problems, lack of information) they tended to emphasize more of the
      interpersonal stressors related to family communication and relationships (e.g.,
      providing and caring for family, distance from family), and intrapersonal
      stressors such as fear, changes in physical appearance, and side effects of
      chemotherapy. Our study illustrates the importance of including multiple
      perspectives. The information gained by including both providers and patient
      perspectives yielded a more complete understanding of the stress management needs
      of Latinas undergoing chemotherapy. Findings suggest that stress management
      educational interventions should aim to develop self-care skills, be culturally
      relevant and language-specific, and build upon stress-reducing strategies Latinas
      may already employ.

PMID- 25952940
TI  - "Burnout in Medical Oncology Fellows: a Prospective Multicenter Cohort Study in
      Brazilian Institutions".
AB  - Burnout syndrome is a common occurrence among oncologists. Doctors enrolled in
      residency programs in clinical oncology are exposed to similar risk factors;
      however, few data are available in this population. This study assessed the
      occurrence of burnout and associated factors among first-year residents at
      Brazilian institutions. The present prospective, multicenter, cohort study was
      conducted with doctors enrolled in residency programs in clinical oncology at
      Brazilian institutions affiliated with the public health system. The participants
      answered a sociodemographic questionnaire, the Maslach Burnout Inventory (MBI),
      Lipp's Stress Inventory, and the Beck Depression Inventory (BDI), upon admission
      to the program and 6 and 12 months later. Of 37 eligible residency programs in
      2009, 11 (30.6 %) agreed to participate in the study. Fifty-four residents,
      representing 100 % of new admissions to the participating institutions, were
      included. Most of the participants met the criteria for severe burnout upon
      admission to the residency programs (emotional exhaustion in 49.0 % and
      depersonalization in 64.7 %). The scores on MBI domains emotional exhaustion and
      depersonalization increased significantly (p < 0.01) during the first year of
      residency, and the prevalence of burnout increased to 88 % at the end of that
      first year. The present study found a high prevalence of burnout among doctors
      enrolled in residency programs in clinical oncology at Brazilian institutions. A
      large fraction of the participants met the criteria for burnout syndrome upon
      admission to the program, which suggests that the problem began during the course
      of the previous residency program in internal medicine.

PMID- 25952941
TI  - Measuring Nutrition Literacy in Breast Cancer Patients: Development of a Novel
      Instrument.
AB  - No nutrition literacy instruments have been tested in breast cancer survivors,
      yet nutrition is a critical lifestyle factor for optimizing weight and improving
      quality of life in breast cancer survival. Our objectives were to adapt our
      Nutrition Literacy Assessment Instrument for breast cancer populations and to
      pilot test its validity and reliability. We modified the instrument based on
      review by content experts in cancer and nutrition and cognitive interviews with
      18 cancer survivors. The modified instrument (Nutrition Literacy Assessment
      Instrument for Breast Cancer, NLit-BCa) was pilot-tested with 17 high-risk women
      and 55 breast cancer survivors. We conducted the NLit-BCa on two separate
      occasions 4 weeks apart and assessed reliability by confirmatory factor analysis.
      Construct validity was evaluated by comparing results of the NLit-BCa to a
      Healthy Eating Index score derived from two separate 24-h dietary recalls.
      Content validity of the NLit-BCa was acceptable (0.93). Entire reliability for
      three instrument domains was substantial (>0.80), while remaining domains
      demonstrated fair or moderate reliability. Significant relationships were found
      between five of the six domains of nutrition literacy and diet quality (P <
      0.05). The NLit-BCa is content valid and demonstrates promising reliability and
      construct validity related to diet quality, through a larger sample size, and
      removal of non-discriminating items is needed to confirm these findings. Thus,
      the NLit-BCa demonstrates potential for comprehensively measuring nutrition
      literacy in breast cancer populations.

PMID- 25952942
TI  - Combined Minimally Invasive Redo Mitral Surgery and Pectus Excavatum Correction.
AB  - We present a technique of mitral valve surgery performed in a patient with severe
      pectus excavatum and previous Bentall surgery. Neither redo sternotomy nor
      conventional right minithoracotomy were thought to provide adequate surgical
      access to the mitral valve. We therefore opted for a combined procedure
      comprising sternal reconstruction and right minithoracotomy mitral valve
      replacement. The mitral valve was replaced and the sternum reconstructed
      according to the Ravitch technique.

PMID- 25952943
TI  - Hyposalivation and dietary nutrient intake among community-based older Japanese.
AB  - AIM: Saliva is important for maintaining oral function and regulating oral
      health. Reduced saliva flow rate, which is common among older adults, has been
      reported to be associated with perceived chewing and swallowing difficulties;
      however, its relationship to actual nutrient intake is unclear. The aim of the
      present cross-sectional study was to evaluate the relationship between
      hyposalivation and nutrient intake among older Japanese adults. METHODS: The
      participants were 352 community-based Japanese aged 80 years. A stimulated
      salivary flow rate <0.5 mL/min was defined as hyposalivation. Multivariable
      analysis of differences in nutrient and food intake outcome variables, which were
      collected through a validated food frequency questionnaire, between groups
      with/without hyposalivation was carried out using general linear models. Models
      included adjustment for number of teeth, denture use, sex, income, education,
      body mass index, smoking status, alcohol use, diabetes, medication, activities of
      daily living, depression and total calorie intake. RESULTS: The hyposalivation
      group had significantly lower intake of n-3 polyunsaturated fatty acid,
      potassium, vitamin D, vitamin E, vitamin B6 and folate than the group without
      hyposalivation (P < 0.05) after adjusting for confounders. Vegetable, fish and
      shellfish consumption was significantly lower in the hyposalivation group (P <
      0.05). CONCLUSIONS: Dietary intake was poorer in those with hyposalivation than
      among those without. A decrease in stimulated salivary flow rate could have
      negative effects on geriatric nutrition.

PMID- 25952944
TI  - A Meta-analytic Review of Non-specific Effects in Randomized Controlled Trials of
      Cognitive Remediation for Schizophrenia.
AB  - Cognitive remediation (CR) has been found to improve cognitive performance among
      adults with schizophrenia in randomized controlled trials (RCTs). However,
      improvements in cognitive performance are often observed in the control groups of
      RCTs as well. There has been no comprehensive examination of change in control
      groups for CR, which may inform trial methodology and improve our understanding
      of measured outcomes for cognitive remediation. In this meta-analysis, we
      calculated pre-post change in cognitive test performance within control groups of
      RCTs in 32 CR trials (n = 794 participants) published between 1970 and 2011, and
      examined the association between pre-post change and sample size, duration of
      treatment, type of control group, and participants' age, intelligence, duration
      of illness, and psychiatric symptoms. Results showed that control groups in CR
      trials showed small effect size changes (Cohen's d = 0.12 +/- 0.16) in cognitive
      test performance over the trial duration. Study characteristics associated with
      pre-post change included participant age and sample size. These findings suggest
      attention to change in control groups may help improve detection of cognitive
      remediation effects for schizophrenia.

PMID- 25952945
TI  - Assessment of Capacity to Consent to Research Among Psychiatric Outpatients:
      Prevalence and Associated Factors.
AB  - Mental capacity is an emerging ethical legal concept in psychiatric settings but
      its relation to clinical parameters remains yet uncertain. The aim of this study
      is to evaluate the association between capacity to consent research and different
      psychiatric disorders and to characterize predictors of impairments in research
      decision-making capacity across diagnostic groups in a cross-sectional study. 139
      consecutively referred outpatients with DSM-IV TR diagnoses of psychotic, mood
      and anxiety disorders were interviewed and a binary judgment of incapacity was
      made guided by the MacArthur competence assessment tool for consent research
      (MacCAT-CR). Demographics and clinical information were assessed by cases notes.
      Patients with anxiety disorders performed the best on the MacCAT-CR, and patients
      with psychotic disorders had the worst performance, however, there was
      considerable heterogeneity within each group. Cognitive impairment and global
      functioning were strongly correlated with MacCAT-CR subscales scores. 30.6%
      participants lacked research-related decisional capacity. Low Understanding score
      OR 0.07 (IC 95% 0.01-0.32) and Low Reasoning score OR 0.30 (IC 95% 0.11-0.82)
      were the factors most closely associated with lack of capacity. No absolute
      statements about decisional capacity can be driven merely due to the diagnosis.
      We found several risk factors which may be considered to decide which populations
      may require more thorough capacity assessments. The issues under consideration in
      the present study are by no means unique to people with psychiatric conditions.
      Ignoring this caveat, risks further inappropriate stigmatization of those with
      serious mental illness.

PMID- 25952946
TI  - Modifications of collagen-based biomaterials with immobilized growth factors or
      peptides.
AB  - In order to provide an instructive microenvironment to facilitate cellular
      behaviors and tissue regeneration, biomaterials can be modified by immobilizing
      growth factors or peptides. We describe here our procedure for modification of
      collagen-based biomaterials, both porous scaffolds and hydrogel systems, with
      growth factors or peptides by covalent immobilization. Characterizations of the
      modified biomaterials (immobilization efficiency, release profile, morphology,
      mechanical strength, and rheology) and in vitro testing with cells are also
      discussed. 

PMID- 25952947
TI  - An Imaging Flow Cytometry-based approach to analyse the fission yeast cell cycle
      in fixed cells.
AB  - Fission yeast (Schizosaccharomyces pombe) is an excellent model organism for
      studying eukaryotic cell division because many of the underlying principles and
      key regulators of cell cycle biology are conserved from yeast to humans. As such
      it can be employed as tool for understanding complex human diseases that arise
      from dis-regulation in cell cycle controls, including cancers. Conventional Flow
      Cytometry (CFC) is a high-throughput, multi-parameter, fluorescence-based single
      cell analysis technology. It is widely used for studying the mammalian cell cycle
      both in the context of the normal and disease states by measuring changes in DNA
      content during the transition through G1, S and G2/M using fluorescent DNA
      binding dyes. Unfortunately analysis of the fission yeast cell cycle by CFC is
      not straightforward because, unlike mammalian cells, cytokinesis occurs after S
      phase meaning that bi-nucleated G1 cells have the same DNA content as mono
      nucleated G2 cells and cannot be distinguished using total integrated
      fluorescence (pulse area). It has been elegantly shown that the width of the DNA
      pulse can be used to distinguish G2 cells with a single 2C foci versus G1 cells
      with two 1C foci, however the accuracy of this measurement is dependent on the
      orientation of the cell as it traverses the laser beam. To this end we sought to
      improve the accuracy of the fission yeast cell cycle analysis and have developed
      an Imaging Flow Cytometry (IFC)-based method that is able to preserve the high
      throughput, objective analysis afforded by CFC in combination with the spatial
      and morphometric information provide by microscopy. We have been able to derive
      an analysis framework for subdividing the yeast cell cycle that is based on
      intensiometric and morphometric measurements and is thus robust against
      orientation-based miss-classification. In addition we can employ image-based
      metrics to define populations of septated/bi-nucleated cells and measure cellular
      dimensions. To our knowledge, this is the first use of IFC to study fission yeast
      and we are confident that this will provide a springboard for further IFC-based
      analysis across all aspects of fission yeast biology. 

PMID- 25952948
TI  - Exploiting the multiplexing capabilities of tandem mass tags for high-throughput
      estimation of cellular protein abundances by mass spectrometry.
AB  - The generation of dynamic models of biological processes critically depends on
      the determination of precise cellular concentrations of biomolecules.
      Measurements of system-wide absolute protein levels are particularly valuable
      information in systems biology. Recently, mass spectrometry based proteomics
      approaches have been developed to estimate protein concentrations on a proteome
      wide scale. However, for very complex proteomes, fractionation steps are
      required, increasing samples number and instrument analysis time. As a result,
      the number of full proteomes that can be routinely analyzed is limited. Here we
      combined absolute quantification strategies with the multiplexing capabilities of
      isobaric tandem mass tags to determine cellular protein abundances in a high
      throughput and proteome-wide scale even for highly complex biological systems,
      such as a whole human cell line. We generated two independent data sets to
      demonstrate the power of the approach regarding sample throughput, dynamic range,
      quantitative precision and accuracy as well as proteome coverage in comparison to
      existing mass spectrometry based strategies. 

PMID- 25952949
TI  - Anti-inflammatory effects of hinokitiol on human corneal epithelial cells: an in
      vitro study.
AB  - PURPOSE: This study assessed the anti-inflammatory effect and mechanism of action
      of hinokitiol in human corneal epithelial (HCE) cells. METHODS: HCE cells were
      incubated with different concentrations of hinokitiol or dimethylsulfoxide
      (DMSO), which served as a vehicle control. Cell viability was evaluated using
      Cell Counting Kit-8 (CCK-8) assay. After polyriboinosinic:polyribocytidylic acid
      (poly(I:C)) stimulus, cells with or without hinokitiol were evaluated for the
      mRNA and protein levels of interleukin-8 (IL-8), interleukin-6 (IL-6), and
      interleukin-1beta (IL-1beta) using real-time PCR analysis and an enzyme-linked
      immunosorbent assay (ELISA), respectively. Nuclear and cytoplasmic levels of
      nuclear factor kappa B (NF-kappaB) p65 protein and an inhibitor of NF-kappaB
      alpha (IkappaBalpha) were evaluated using western blotting. RESULTS: There were
      no significant differences among the treatment concentrations of hinokitiol
      compared with cells incubated in medium only. Incubating with 100 MUM hinokitiol
      significantly decreased the mRNA levels of IL-8 to 58.77+/-10.41% (P<0.01), IL-6
      to 64.64+/-12.71% (P<0.01), and IL-1beta to 54.19+/-8.10% (P<0.01) compared with
      cells stimulated with poly(I:C) alone. The protein levels of IL-8, IL-6, and IL
      1beta had similar trend. Further analysis revealed that hinokitiol maintained the
      levels of IkappaBalpha and significantly reduced NF-kappaB p65 subunit
      translocation to the nucleus which significantly inhibiting the activation of the
      NF-kappaB signal pathway. CONCLUSION: Hinokitiol showed a significant protective
      effect against ocular surface inflammation through inhibiting the NF-kappaB
      pathway, which may indicate the possibility to relieve the ocular surface
      inflammation of dry eye syndrome (DES).

PMID- 25952950
TI  - Correlation of structure and function of the macula in patients with retinitis
      pigmentosa.
AB  - PURPOSE: To correlate the structure of the macula, as measured by spectral-domain
      optical coherence tomography (SD-OCT) and function, as measured by microperimetry
      (MAIA) in patients with retinitis pigmentosa (RP) and relatively good visual
      acuity. DESIGN: Prospective, cross-sectional, non-intervention study. SUBJECTS:
      Patients with RP. METHODS: Thirty patients with RP and good central visual acuity
      were identified. Each patient underwent SD-OCT of the macula and microperimetry.
      The images were overlaid using the custom-designed software. The retinal
      sensitivity by microperimetry was correlated with corresponding retinal
      thickness, as measured by the SD-OCT. ELM, COST, and IS/OS junction were scored
      as intact, disrupted, or absent. MAIN OUTCOME MEASURES: Comparing the retinal
      sensitivity on the MAIA with various measurements on the SD-OCT. RESULTS: The
      retinal sensitivity on the MAIA showed a significant correlation with total
      retinal thickness and outer retinal thickness on the SD-OCT. There was no
      association with either the inner retinal thickness or the choroidal thickness.
      ORT showed a statistically significant correlation with the anatomical
      classification of ELM (r=-0.76, P<0.001), IS/OS (r=-0.800, P<0.001), and COST (r=
      0.733, P<0.001). CONCLUSION: This study determined that there was a high
      correlation of the structure and function of the central macula in patients with
      RP. These studies are important to establish surrogate markers that can be used
      as end points for various tests in future therapeutic clinical trials.

PMID- 25952952
TI  - Meta consent: a flexible and autonomous way of obtaining informed consent for
      secondary research.

PMID- 25952951
TI  - Clinical characteristics of responders to intravitreal bevacizumab in central
      serous chorioretinopathy patients.
AB  - PURPOSE: To investigate factors associated with good response to intravitreal
      bevacizumab (IVB) in central serous chorioretinopathy (CSC) patients. METHODS: We
      retrospectively reviewed 42 eyes of CSC patients of symptom duration more than 3
      months who received a single or multiple successive IVBs on an as-needed basis
      (0.05 ml, 1.25 mg). High responders (HRs) were defined as complete resolution of
      subretinal fluid (SRF) on spectral domain optical coherence tomography (SD-OCT).
      Moderate responders (MRs) were defined as SRF resolution of 50-99% of
      pretreatment volume and poor responders (PRs) as SRF resolution <50%. Clinical,
      SD-OCT, fluorescein, and indocyanine green angiography findings were analyzed to
      find factors associated with HR. Descriptive statistics for all demographic and
      clinical variables were calculated, and comparisons were made using Wilcoxon's
      matched-pairs signed-rank test, the Mann-Whitney U-test for means with continuous
      data, Pearson's chi(2) test, and Fisher's exact test for categorical data.
      RESULTS: The mean number of IVB was 1.9. At postoperative 1 month, there were 10
      (24%) HRs, 18 (43%) MRs, and 14 (33%) PRs. At the last follow-up (the mean 8.6
      months), there were 25 HRs (60%), 9 MRs (21%), and 8 PRs (19%). Thicker subfoveal
      choroid (P=0.036), smaller lesion diameter (P=0.019), and better baseline best
      corrected visual acuity (P=0.002) predicted HRs at postoperative 1 month. HR at
      the last follow-up was associated with classic pattern fluorescein angiography
      finding. CONCLUSIONS: Suboptimal effects of IVB on persistent CSC suggest primary
      IVB on selective cases with better vision, smaller lesion, and thicker choroid at
      baseline.

PMID- 25952953
TI  - Nanoscale Heterogeneity of the Molecular Structure of Individual hIAPP Amyloid
      Fibrils Revealed with Tip-Enhanced Raman Spectroscopy.
AB  - Type 2 diabetes mellitus is characterized by the pathological deposition of
      fibrillized protein, known as amyloids. It is thought that oligomers and/or
      amyloid fibrils formed from human islet amyloid polypeptide (hIAPP or amylin)
      cause cell death by membrane damage. The molecular structure of hIAPP amyloid
      fibrils is dominated by beta-sheet structure, as probed with conventional
      infrared and Raman vibrational spectroscopy. However, with these techniques it is
      not possible to distinguish between the core and the surface structure of the
      fibrils. Since the fibril surface crucially affects amyloid toxicity, it is
      essential to know its structure. Here the surface molecular structure and amino
      acid residue composition of hIAPP fibrils are specifically probed with nanoscale
      resolution using tip-enhanced Raman spectroscopy (TERS). The fibril surface
      mainly contains unordered or alpha-helical structures, in contrast to the beta
      sheet-rich core. This experimentally validates recent models of hIAPP amyloids
      based on NMR measurements. Spatial mapping of the surface structure reveals a
      highly heterogeneous surface structure. Finally, TERS can probe fibrils formed on
      a lipid interface, which is more representative of amyloids in vivo. 

PMID- 25952954
TI  - Thyroid gland metastasis of rectal cancer.
AB  - A 72-year-old woman with a history of rectal cancer was admitted to our hospital
      to undergo thyroidectomy and left adrenalectomy. She had undergone low anterior
      resection and regional lymph node dissection for rectal cancer 52 months pre
      admission (T3 N1 M0, stage IIIb according to International Union Against Cancer
      tumor-node-metastasis), and she had also undergone metastasectomy for lung
      metastases and right adrenal gland metastasis after the rectal surgery. Follow-up
      computed tomography scans detected nodules in the bilateral lobes of the thyroid
      gland and in the left adrenal gland. Subtotal thyroidectomy and left
      adrenalectomy were performed, and pathological examination revealed metastases of
      rectal cancer to the thyroid gland and left adrenal gland. 

PMID- 25952955
TI  - Reduction en masse can be treated using pure laparoscopic transabdominal
      preperitoneal hernioplasty following early CT diagnosis: report of a case.
AB  - Reduction en masse refers to the rare occurrence of an incarcerated inguinal
      hernia arising from the manual reduction of a hernia. Such a condition
      constitutes a medical emergency because the hernia contents, such as the small
      bowel, remain strangulated in the preperitoneal space. Therefore, an early and
      accurate diagnosis, with early treatment, is important. A 61-year-old Japanese
      man presented with an irreducible lump over his left groin, leading to the
      reduction of an incarcerated inguinal hernia by a doctor at another hospital.
      Later, he was admitted to our hospital with vomiting and abdominal pain. Computed
      tomography showed a ball-like lesion containing an incarcerated bowel loop over
      his left pelvis. The patient was diagnosed with an incarcerated small bowel
      obstruction due to a reduction en masse; a laparoscopic transabdominal
      preperitoneal (TAPP) hernioplasty was performed. TAPP hernioplasty is a safe
      method for treating reductions en masse that allows confirmation of bowel
      viability. 

PMID- 25952956
TI  - Multiple thoracic duct cysts: an unusual CT finding.
AB  - Thoracic duct cysts in the mediastinum are rare. We report the case of a 66-year
      old gentleman who was found to have multiple small thoracic duct cysts during
      investigation of a retrosternal thyroid goitre. Multiple paraoesphageal swellings
      were seen on a computed tomographic scan in the upper posterior mediastinum. The
      largest was 2 cm and they were continuous with the thoracic duct. This is this
      first reported case of multiple thoracic duct cysts. Previous cases are of a
      single large swelling, the majority of which were surgically excised. Small
      asymptomatic cysts such as the case we present are suitable for conservative
      management. 

PMID- 25952957
TI  - The new hybrids: Continuing debates on social perception.
AB  - I evaluate several attempts to integrate standard theories of social cognition,
      either theory theory or simulation theory, with aspects of interaction theory,
      and especially with the concept of direct social perception. I refer to these as
      new hybrid theories of social cognition. One of the new hybrids accomplishes the
      integration only by weakening the concept of mindreading or by understanding
      mindreading as targeting the shared situation rather than the other's mental
      states. Hybrids that attempt to accommodate the idea of direct perception of
      mental states grant a phenomenological directness only by maintaining tacit
      (theory-based) inferences on the subpersonal level. If such inferential processes
      are thought to be extra-perceptual, then perception is neither sufficient nor
      direct for an understanding of intentions and emotions. Moreover, insistence on
      top-down inferential processes trades off against the possibility of plasticity
      in the perceptual system itself. I suggest that a better model than a hybrid
      theory would be a pluralist one. A pluralist approach to social cognition would
      treat theoretical inference, simulation, direct perception, interactive skills,
      etc. as different strategies. The real challenge is to work out a pluralist
      account of subpersonal processes. 

PMID- 25952958
TI  - A new family of anionic organic-inorganic hybrid doughnut-like nanostructures.
AB  - A family of soluble organic-inorganic hybrid doughnut-like anions, hydoughnuts,
      has been prepared by the self-assembly of polyoxovanadate anions and 1,3
      benzenedicarboxylate (bdc) linkers. Derivatives of the parent hydoughnut,
      [(V4O8Cl)4(bdc)8](4-), can be obtained by changing the counter-ion or by using a
      variant of bdc. 

PMID- 25952959
TI  - Clinically meaningful parameters of progression and long-term outcome of
      Parkinson disease: An international consensus statement.
AB  - Parkinson disease (PD) is associated with a clinical course of variable duration,
      severity, and a combination of motor and non-motor features. Recent PD research
      has focused primarily on etiology rather than clinical progression and long-term
      outcomes. For the PD patient, caregivers, and clinicians, information on expected
      clinical progression and long-term outcomes is of great importance. Today, it
      remains largely unknown what factors influence long-term clinical progression and
      outcomes in PD; recent data indicate that the factors that increase the risk to
      develop PD differ, at least partly, from those that accelerate clinical
      progression and lead to worse outcomes. Prospective studies will be required to
      identify factors that influence progression and outcome. We suggest that data for
      such studies is collected during routine office visits in order to guarantee high
      external validity of such research. We report here the results of a consensus
      meeting of international movement disorder experts from the Genetic Epidemiology
      of Parkinson's Disease (GEO-PD) consortium, who convened to define which long
      term outcomes are of interest to patients, caregivers and clinicians, and what is
      presently known about environmental or genetic factors influencing clinical
      progression or long-term outcomes in PD. We propose a panel of rating scales that
      collects a significant amount of phenotypic information, can be performed in the
      routine office visit and allows international standardization. Research into the
      progression and long-term outcomes of PD aims at providing individual prognostic
      information early, adapting treatment choices, and taking specific measures to
      provide care optimized to the individual patient's needs. 

PMID- 25952960
TI  - Tremor-related quality of life: A comparison of essential tremor vs. Parkinson's
      disease patients.
AB  - BACKGROUND: Tremor-related quality of life is a multi-dimensional concept that
      reflects the physical, emotional and other health effects of tremor. Curiously,
      tremor-related quality of life has never been directly compared in patients with
      the two major tremor disorders, essential tremor (ET) and Parkinson's disease
      (PD). We performed a head-to-head comparison of ET with PD patients. METHODS: The
      Quality of Life in Essential Tremor (QUEST) questionnaire was administered to 103
      ET and 103 matched PD patients enrolled in a clinical-epidemiological study in
      New York. RESULTS: The QUEST total score and QUEST physical subscore were higher
      in ET than PD patients (both p < 0.05). In relative terms, ET patients reported
      significantly more impairment than PD patients in multiple areas; PD patients
      reported more impairment than ET patients in one area (all p <= 0.02). In
      absolute terms, tremor impacted on many aspects of quality of life in both
      diseases, including physical and psychosocial, and in one-third or more of PD
      patients, tremor sometimes, frequently or always interfered with numerous
      physical activities, including writing, using a typewriter/computer, fixing small
      things, dressing, eating, and holding reading material. CONCLUSIONS: Tremor is a
      clinical entity that can have numerous effects on patients. While there were
      relative differences between the two major tremor disorders, ET and PD, in
      absolute terms, tremor impacted on several domains of quality of life, from
      physical to psychosocial, in a large proportion of ET and PD patients. Attempts
      to judge the efficacy of treatments for tremor, whether pharmacological or
      surgical, should consider its broad impact.

PMID- 25952961
TI  - Association of LRRK2 and GBA mutations in a Brazilian family with Parkinson's
      disease.

PMID- 25952962
TI  - The sensory timecourses associated with conscious visual item memory and source
      memory.
AB  - Previous event-related potential (ERP) findings have suggested that during visual
      item and source memory, nonconscious and conscious sensory (occipital-temporal)
      activity onsets may be restricted to early (0-800 ms) and late (800-1600 ms)
      temporal epochs, respectively. In an ERP experiment, we tested this hypothesis by
      separately assessing whether the onset of conscious sensory activity was
      restricted to the late epoch during source (location) memory and item (shape)
      memory. We found that conscious sensory activity had a late (>800 ms) onset
      during source memory and an early (<200 ms) onset during item memory. In a follow
      up fMRI experiment, conscious sensory activity was localized to BA17, BA18, and
      BA19. Of primary importance, the distinct source memory and item memory ERP
      onsets contradict the hypothesis that there is a fixed temporal boundary
      separating nonconscious and conscious processing during all forms of visual
      conscious retrieval.

PMID- 25952963
TI  - An fMRI study of the functional mechanisms of Stroop/reverse-Stroop effects.
AB  - Many previous behavioral inhibition studies have employed the classic Stroop and
      reverse-Stroop paradigm. Although an experimental dissociation has been
      demonstrated between Stroop interference (SI) and reverse-Stroop interference
      (RI), the mechanisms that underlie these phenomena remain unclear. In this study,
      we used functional magnetic resonance imaging (fMRI) to compare the functional
      mechanisms of SI and RI. We identified the brain regions activated by the Stroop
      word-color matching task using four tests: the Stroop control test (Test 1),
      Stroop test (Test 2), reverse-Stroop control test (Test 3), and reverse-Stroop
      test (Test 4). Neuroimaging results revealed that SI elicited activation in the
      bilateral middle frontal gyrus (BA9). In contrast, a number of other regions,
      including the bilateral middle frontal gyrus (BA 9 and BA10), medial frontal
      gyrus (BA 8), and cingulate gyrus (BA6 and BA 32) exhibited significant
      activation during RI. Our results indicate that there is a dissociation between
      the types of interference and brain activation. These findings suggest that SI
      and RI interference can be attributable to different neural mechanisms. It also
      suggests that the prefrontal cortex and the cingulate cortex are differentially
      sensitive to various types of interference, and that the reverse-Stroop task may
      be more useful than the Stroop task for evaluating interference control in
      psychiatric patients with frontal dysfunction. 

PMID- 25952964
TI  - 3D Is It a Better Choice for All, or for Some?

PMID- 25952965
TI  - Bioethical challenges of the Ebola outbreak.

PMID- 25952966
TI  - In that case: necessary limitation of medical treatment, ageism, or worse? A
      policy proposal for limiting kidney dialysis availability over 75.

PMID- 25952967
TI  - Human bone marrow stem cells cultured under hypoxic conditions present altered
      characteristics and enhanced in vivo tissue regeneration.
AB  - Human bone marrow mesenchymal stem cells (hBMSCs) were isolated from bone marrow
      of the vertebral body. The hBMSCs were cultured under either hypoxic (1% O2) or
      normoxic (21% O2; control) conditions and the characteristics as mesenchymal stem
      cells were compared. Results revealed that hypoxia reduced proliferative
      potential and colony-forming efficiency of hBMSCs, and significantly enhanced
      osteogenic and chondrogenic differentiation. The hBMSCs enhanced the regenerative
      potential of bone in vivo. In vitro synthesis of soluble and insoluble collagen
      was significantly increased in the hypoxic condition. In vivo collagen tissue
      regeneration was also enhanced under the hypoxic condition, with concomitant
      increased expressions of various subtypes of collagen and lysyl-oxidase family
      mRNA. MicroRNA assays revealed that miR-155-5p, which negatively regulates HIF
      1alpha, was significantly highly expressed. These observations demonstrate that
      hBMSCs obtained from human vertebrae exhibit altered characteristics under
      hypoxic conditions, and each factor contributing to hBMSC-mediated tissue healing
      should be evaluated with the goal of allowing their clinical application. 

PMID- 25952968
TI  - Association between bone stiffness and nutritional biomarkers combined with
      weight-bearing exercise, physical activity, and sedentary time in preadolescent
      children. A case-control study.
AB  - Physical activity (PA) and micronutrients such as calcium (Ca), vitamin D
      (25OHD), and phosphate (PO) are important determinants of skeletal development.
      This case-control study examined the association of these nutritional biomarkers
      and different PA behaviours, such as habitual PA, weight-bearing exercise (WBE)
      and sedentary time (SED) with bone stiffness (SI) in 1819 2-9-year-old children
      from the IDEFICS study (2007-2008). SI was measured on the calcaneus using
      quantitative ultrasound. Serum and urine Ca and PO and serum 25OHD were
      determined. Children's sports activities were reported by parents using a
      standardised questionnaire. A subsample of 1089 children had accelerometer-based
      PA data (counts per minute, cpm). Moderate-to-vigorous PA (MVPA) and SED were
      estimated. Children with poor SI (below the 15th age-/sex-/height-specific
      percentile) were defined as cases (N=603). Randomly selected controls (N=1216)
      were matched by age, sex, and country. Odds ratios (OR) for poor SI were
      calculated by conditional logistic regression for all biomarkers and PA behaviour
      variables separately and combined (expressed as tertiles and dichotomised
      variables, respectively). ORs were adjusted for fat-free mass, dairy product
      consumption, and daylight duration. We observed increased ORs for no sports
      (OR=1.39, p<0.05), PA levels below 524 cpm (OR=1.85, p<0.05) and MVPA below 4.2%
      a day (OR=1.69, p<0.05) compared to WBE, high PA levels (<688 cpm) and high MVPA
      (6.7%), respectively. SED was not associated with SI. ORs were moderately
      elevated for low serum Ca and 25OHD. However, biomarkers were not statistically
      significantly associated with SI and did not modify the association between PA
      behaviours and SI. Although nutritional biomarkers appear to play a minor role
      compared to the osteogenic effect of PA and WBE, it is noteworthy that the
      highest risk for poor SI was observed for no sports or low MVPA combined with
      lower serum Ca (<2.5 mmol/l) or lower 25OHD (<43.0 nmol/l).

PMID- 25952970
TI  - Bone metastasis in prostate cancer: Recurring mitochondrial DNA mutation reveals
      selective pressure exerted by the bone microenvironment.
AB  - BACKGROUND: Cancer progression and metastasis occur such that cells with acquired
      mutations enhancing growth and survival (or inhibiting cell death) increase in
      number, a concept that has been recognized as analogous to Darwinian evolution of
      species since Peter C. Nowell's description in 1976. Selective forces include
      those intrinsic to the host (including metastatic site) as well as those
      resulting from anti-cancer therapies. By examining the mutational status of
      multiple tumor sites within an individual patient some insight may be gained into
      those genetic variants that enhance site-specific metastasis. By comparing these
      data across multiple individuals, recurrent patterns may identify alterations
      that are fundamental to successful site-specific metastasis. METHODS: We
      sequenced the mitochondrial genome in 10 prostate cancer patients with bone
      metastases enrolled in a rapid autopsy program. Patients had late stage disease
      and received androgen ablation and frequently other systemic therapies. For each
      of 9 patients, 4 separate tissues were sequenced: the primary prostate cancer, a
      soft tissue metastasis, a bone metastasis and an uninvolved normal tissue that
      served as the non-cancerous control. An additional (10th) patient had no primary
      prostate available for sequencing but had both metastatic sites (and control DNA)
      sequenced. We then examined the number and location of somatically acquired
      mitochondrial DNA (mtDNA) mutations in the primary tumor and two metastatic sites
      in each individual patient. Finally, we compared patients with each other to
      determine any common patterns of somatic mutation. RESULTS: Somatic mutations
      were significantly more numerous in the bone compared to either the primary tumor
      or soft tissue metastases. A missense mutation at nucleotide position (n.p.)
      10398 (A10398G; Thr114Ala) in the respiratory complex I gene ND3 was the most
      common (7 of 10 patients) and was detected only in the bone. Other notable
      somatic mutations that occurred in more than one patient include a tRNA Arg
      mutation at n.p. 10436 and a tRNA Thr mutation at n.p. 15928. The tRNA Arg
      mutation was restricted to bone metastases and occurred in three of 10 patients
      (30%). Somatic mutation at 15928 was not restricted to the bone and also occurred
      in three patients. CONCLUSIONS: Mitochondrial genomic variation was greater in
      metastatic sites than in the primary tumor and bone metastases had statistically
      significantly greater numbers of somatic mutations than either the primary or the
      soft tissue metastases. The genome was not mutated randomly. At least one
      mutational "hot-spot" was identified at the individual base level (nucleotide
      position 10398 in bone metastases) indicating a pervasive selective pressure for
      bone metastatic cells that had acquired the 10398 mtDNA mutation. Two additional
      recurrent mutations (tRNA Arg and tRNA Thr) support the concept of bone site
      specific "survival of the fittest" as revealed by variation in the mitochondrial
      genome and selective pressure exerted by the metastatic site.

PMID- 25952971
TI  - Effects of parathyroid hormone on cortical porosity, non-enzymatic glycation and
      bone tissue mechanics in rats with type 2 diabetes mellitus.
AB  - Type 2 diabetes mellitus increases skeletal fragility; however, the contributing
      mechanisms and the efficacy of bone-forming agents are unclear. We studied
      diabetes and parathyroid hormone (PTH) treatment effects on cortical porosity
      (Ct.Po), non-enzymatic glycation (NEG) and bone mechanics in Zucker diabetic
      fatty (ZDF) rats. Eleven-week old ZDF diabetic (DB) and non-diabetic (ND) rats
      were given 75MUg/kg PTH (1-84) or vehicle 5days per week over 12weeks. The right
      femora and L4 vertebrae were excised, micro-CT scanned, and tested in 3-point
      bending and uniaxial compression, respectively. NEG of the samples was determined
      using fluorescence. Diabetes increased Ct.Po (vertebra (vert): +40.6%, femur
      (fem): +15.5% vs. ND group, p<0.05) but had no effect on NEG. PTH therapy reduced
      vertebral NEG in the ND animals only (-73% vs untreated group, p<0.05), and
      increased femoral NEG in the DB vs. ND groups (+63%, p<0.05). PTH therapy had no
      effect on Ct.Po. Diabetes negatively affected bone tissue mechanics where
      reductions in vertebral maximum strain (-22%) and toughness (-42%) were observed
      in the DB vs. ND group (p<0.05). PTH improved maximum strain in the vertebra of
      the ND animals (+21%, p<0.05) but did not have an effect in the DB group. PTH
      increased femoral maximum strain (+21%) and toughness (+28%) in ND and decreased
      femoral maximum stress (-13%) and toughness (-27%) in the DB animals (treated vs.
      untreated, p<0.05). Ct.Po correlated negatively with maximum stress (fem: R=
      0.35, p<0.05, vert: R=-0.57, p<0.01), maximum strain (fem: R=-0.35, p<0.05, vert:
      R=-0.43, p<0.05) and toughness (fem: R=-0.34, p<0.05, vert: R=-0.55, p<0.01), and
      NEG correlated negatively with toughness at the femur (R=-0.34, p<0.05) and
      maximum strain at the vertebra (R=-0.49, p<0.05). Diabetes increased cortical
      porosity and reduced bone mechanics, which were not improved with PTH treatment.
      PTH therapy alone may worsen diabetic bone mechanics through formation of new
      bone with high AGEs cross-linking. Optimal treatment regimens must address both
      improvements of bone mass and glycemic control in order to successfully reduce
      diabetic bone fragility. This article is part of a Special Issue entitled "Bone
      and diabetes". 

PMID- 25952969
TI  - Sclerostin antibody treatment improves fracture outcomes in a Type I diabetic
      mouse model.
AB  - Type 1 diabetes mellitus (T1DM) patients have osteopenia and impaired fracture
      healing due to decreased osteoblast activity. Further, no adequate treatments are
      currently available that can restore impaired healing in T1DM; hence a
      significant need exists to investigate new therapeutics for treatment of
      orthopedic complications. Sclerostin (SOST), a WNT antagonist, negatively
      regulates bone formation, and SostAb is a potent bone anabolic agent. To
      determine whether SOST antibody (SostAb) treatment improves fracture healing in
      streptozotocin (STZ) induced T1DM mice, we administered SostAb twice weekly for
      up to 21days post-fracture, and examined bone quality and callus outcomes at
      21days and 42days post-fracture (11 and 14weeks of age, respectively). Here we
      show that SostAb treatment improves bone parameters; these improvements persist
      after cessation of antibody treatment. Markers of osteoblast differentiation such
      as Runx2, collagen I, osteocalcin, and DMP1 were reduced, while an abundant
      number of SP7/osterix-positive early osteoblasts were observed on the bone
      surface of STZ calluses. These results suggest that STZ calluses have poor
      osteogenesis resulting from failure of osteoblasts to fully differentiate and
      produce mineralized matrix, which produces a less mineralized callus. SostAb
      treatment enhanced fracture healing in both normal and STZ groups, and in
      STZ+SostAb mice, also reversed the lower mineralization seen in STZ calluses.
      Micro-CT analysis of calluses revealed improved bone parameters with SostAb
      treatment, and the mineralized bone was comparable to Controls. Additionally, we
      found sclerostin levels to be elevated in STZ mice and beta-catenin activity to
      be reduced. Consistent with its function as a WNT antagonist, SostAb treatment
      enhanced beta-catenin activity, but also increased the levels of SOST in the
      callus and in circulation. Our results indicate that SostAb treatment rescues the
      impaired osteogenesis seen in the STZ induced T1DM fracture model by facilitating
      osteoblast differentiation and mineralization of bone. 

PMID- 25952972
TI  - Egfl6 is involved in zebrafish notochord development.
AB  - The epidermal growth factor (EGF) repeat motif defines a superfamily of diverse
      protein involved in regulating a variety of cellular and physiological processes,
      such as cell cycle, cell adhesion, proliferation, migration, and neural
      development. Egfl6, an EGF protein, also named MAGE was first cloned in human
      tissue. Up to date, the study of zebrafish Egfl6 expression pattern and
      functional analysis of Egfl6 involved in embryonic development of vertebrate in
      vivo is thus far lacking. Here we reported that Egfl6 was involved in zebrafish
      notochord development. It was shown that Egfl6 mRNA was expressed in zebrafish,
      developing somites, fin epidermis, pharyngeal arches, and hindbrain region.
      Particularly the secreted Egfl6 protein was significantly accumulated in
      notochord. Loss of Egfl6 function in zebrafish embryos resulted in curved body
      with distorted notochord in the posterior trunk. It was observed that expression
      of all Notch ligand and receptors in notochord of 28 hpf Egfl6 morphants was not
      affected, except notch2, which was up-regulated. We found that inhibition of
      Notch signaling by DAPT efficiently rescued notochord developmental defect of
      Egfl6 deficiency embryos. 

PMID- 25952973
TI  - Effects of glucose, insulin and triiodothyroxine on leptin and leptin receptor
      expression and the effects of leptin on activities of enzymes related to glucose
      metabolism in grass carp (Ctenopharyngodon idella) hepatocytes.
AB  - Leptin is an important regulator of appetite and energy expenditure in mammals,
      but its role in fish metabolism control is poorly understood. Our previous
      studies demonstrated that leptin has an effect on the regulation of food intake
      and energy expenditure as well as lipid metabolism (stimulation of lipolysis and
      inhibition of adipogenesis) in the grass carp Ctenopharyngodon idella. To further
      investigate the role of leptin in fish, the effects of glucose, insulin and
      triiodothyroxine (T3) on the expression levels of leptin and leptin receptor
      (Lepr) and the effects of leptin on the activities of critical glucose metabolism
      enzymes in grass carp hepatocytes were evaluated in the present study. Our data
      indicated that leptin gene expression was induced by glucose in a dose-dependent
      manner, while Lepr gene expression exhibited a biphasic change. A high dose of
      insulin (100 ng/mL) significantly up-regulated the expression of leptin and Lepr.
      Leptin expression was markedly up-regulated by a low concentration of T3 but
      inhibited by a high concentration of T3. T3 up-regulated Lepr expression in a
      dose-dependent manner. Together, these data suggest that leptin had a close
      relationship with three factors (glucose, insulin and T3) and might participate
      in the regulation of glucose metabolism in grass carp. In addition, we also found
      that leptin affected the activities of key enzymes that are involved in glucose
      metabolism, which might be mediated by insulin receptor substrate-phosphoinositol
      3-kinase signaling. 

PMID- 25952974
TI  - Hunter syndrome with its typical heart: a close mimic to rheumatic heart.
AB  - A 24-year-old man presented with New York Heart Association (NYHA) grade 3
      dyspnoea. He appeared dwarf-like with coarse facial features. General examination
      revealed cubitus valgus, claw hand, genu valgus, hallus valgus and equinovarus
      deformity of the foot. Systemic examination revealed cardiomegaly, a pansystolic
      mitral regurgitation (MR) murmur, hepatosplenomegaly and a normal IQ. Examination
      suggested multisystem disease involving the dermatological, musculoskeletal,
      cardiac and gastrointestinal system. Echocardiography showed thickened mitral and
      aortic valves, and moderate MR. We considered this as a storage disorder,
      particularly the mucopolysaccharidosis, because of its typical cardiac
      involvement. Further evaluation confirmed the diagnosis of Hunter syndrome. The
      patient was considered for enzyme replacement therapy, following which he
      improved. This rare disease must be considered whenever a physician encounters a
      young patient with multisystem involvement. In view of the availability of
      disease-specific therapy, an early diagnosis and prompt treatment with a
      multidisciplinary approach can improve the quality of life of these patients. 

PMID- 25952976
TI  - The human balance system and gender.
AB  - The human body balance system is a complex system of organs and mechanisms, which
      generate postural reactions to counter the displacement from the equilibrium
      position of the body centre of gravity, and which control eye movement in order
      to maintain a stable image of the environment. Computerised Dynamic Posturography
      (CDP) allows for a quantitative and objective assessment of the sen- sory and
      motor components of the body balance control system as well as of the integration
      and adaptive mechanisms in the central nervous system. The aim of this study was
      to determine the differences, when maintaining body balance, based on the gender
      of young, healthy people using CDP. The study was carried out on a group of 43
      healthy subjects by comparing the effectiveness of the balance system in 22 women
      and 21 men aged between 20 and 26 years, between 171 and 177 cm in height, and
      without any clinical symptoms of balance disorders. The men and women were
      selected such that they did not differ significantly in height and BMI. Using the
      Equitest posturograph manufactured by NeuroCom International Inc. the following
      tests were performed: Sensory Organisation Test (SOT), Motor Control Test (MCT)
      and the Adaptation Test (ADT). The gender of young healthy individuals without
      any clinical symptoms of balance disorders also does not affect the effectiveness
      of the sensory system and the use of this signal in maintaining body balance. 

PMID- 25952977
TI  - Long-term prophylaxis in severe factor VII deficiency.
AB  - INTRODUCTION: The spectrum of bleeding problems in FVII deficiency is highly
      variable and FVII levels and causative genetic mutations correlate poorly with
      the bleeding risk. Long-term prophylaxis is generally initiated in order to
      prevent subsequent CNS bleeding after a first event or in patients with other
      major/ life threatening/ frequent bleeding symptoms as gastrointestinal bleeding
      or hemarthrosis. However few data are available in the literature regarding FVII
      prophylaxis and clinical decisions cannot be based on evidence. AIMS: We report
      the data available in the literature on FVII prophylaxis and our personal
      experience regarding three patients affected by severe FVII deficiency. METHODS:
      Specific papers on long-term prophylaxis in severe FVII deficiency were
      identified using the database, PUBMED. RESULTS: The most frequent indications for
      long-term prophylaxis were CNS bleeding (58%), hemartrosis (15%) and GI bleeding
      (9%). Patients were treated with various dosages and frequency. Prophylactic
      treatment with 10-30U/kg (pdFVII) or 20-30mcg/kg (rFVIIa) twice or three
      times/weeks was described to be effective. CONCLUSIONS: In the literature and in
      our experience, prophylaxis can be considered in patients with severe FVII
      deficiency and severe bleeding phenotype. A dose of 10-30U/kg (pdFVII) or 20-30
      microg/kg (rFVIIa) twice or three times/week is usually administrated, but dose
      and frequency can be tailored based on the clinical follow-up of the patients.
      Since hemarthrosis is a frequent manifestation, a suggestion to improve the
      outcomes of patients with severe FVII deficiency is to monitor joint condition in
      order to identify early arthropathy that could be another indication to start
      secondary prophylaxis.

PMID- 25952978
TI  - A critical approach toward resonance-assistance in the intramolecular hydrogen
      bond interaction of 3,5-diiodosalicylic acid: a spectroscopic and computational
      investigation.
AB  - The photophysics of a prospective drug molecule, 3,5-diiodosalicylic acid (3,5
      DISA), having a wide spectrum of biological and medicinal applications, have been
      investigated using spectroscopic techniques and computational analyses. The
      remarkably large Stokes' shifts in various solvents from 3,5-DISA has been
      intertwined with the occurrence of an excited-state intramolecular proton
      transfer (ESIPT) reaction. Concurrently, the emergence of an intriguing dual
      emission feature in less interacting solvents is also reported and the spectral
      response of 3,5-DISA toward the variation of medium acidity/basicity has been
      exploited to decipher the nature of various species present in different
      solvents. Our experimental results, unveiling the occurrence of an ESIPT reaction
      in 3,5-DISA, have been aptly substantiated from computational studies in which
      the operation of ESIPT has been explored from structural as well as energetics
      (analysis of potential energy surface (PES)) perspectives. A major focus of the
      present study is on the evaluation of the intramolecular hydrogen bond (IMHB)
      interaction in 3,5-DISA, including the application of various methodologies to
      estimate the IMHB energy and subsequently, an in-depth analysis of the IMHB
      interaction reveals its partially covalent nature through the application of
      advanced quantum chemical tools, e.g., the natural bond orbital (NBO) method. In
      this context, the interplay between the aromaticity of the benzene nucleus and
      the IMHB energy has been rigorously explored, showing indications for the
      occurrence of resonance-assisted hydrogen bonding (RAHB) in 3,5-DISA. To this
      end, the geometric as well as magnetic criteria of aromaticity have been
      analyzed. 

PMID- 25952975
TI  - Origin and differentiation of vascular smooth muscle cells.
AB  - Vascular smooth muscle cells (SMCs), a major structural component of the vessel
      wall, not only play a key role in maintaining vascular structure but also perform
      various functions. During embryogenesis, SMC recruitment from their progenitors
      is an important step in the formation of the embryonic vascular system. SMCs in
      the arterial wall are mostly quiescent but can display a contractile phenotype in
      adults. Under pathophysiological conditions, i.e. vascular remodelling after
      endothelial dysfunction or damage, contractile SMCs found in the media switch to
      a secretory type, which will facilitate their ability to migrate to the intima
      and proliferate to contribute to neointimal lesions. However, recent evidence
      suggests that the mobilization and recruitment of abundant stem/progenitor cells
      present in the vessel wall are largely responsible for SMC accumulation in the
      intima during vascular remodelling such as neointimal hyperplasia and
      arteriosclerosis. Therefore, understanding the regulatory mechanisms that control
      SMC differentiation from vascular progenitors is essential for exploring
      therapeutic targets for potential clinical applications. In this article, we
      review the origin and differentiation of SMCs from stem/progenitor cells during
      cardiovascular development and in the adult, highlighting the environmental cues
      and signalling pathways that control phenotypic modulation within the
      vasculature. 

PMID- 25952979
TI  - First interim analysis of a randomised trial of whole brain radiotherapy in
      melanoma brain metastases confirms high data quality.
AB  - BACKGROUND: Brain metastases are a common cause of death in patients with
      melanoma. The role of adjuvant whole brain radiotherapy (WBRT) following local
      treatment of intracranial melanoma metastases is controversial. The Australian
      and New Zealand Melanoma Trials Group (ANZMTG) and the Trans-Tasman Radiation
      Oncology Group (TROG) are leading the first ever single histology randomised
      trial investigating this question. The primary endpoint is distant intracranial
      failure on magnetic resonance imaging (MRI) within twelve months of
      randomisation. The first planned interim analysis was performed twelve months
      after randomisation of the 100(th) patient. The analysis was an opportunity to
      review completeness of the trial data to date. METHODS: All data received up to
      the end of twelve months after randomisation of the 100th patient was reviewed.
      RESULTS: Review of pathology reports confirmed that all 100 patients had stage IV
      melanoma and were appropriately entered into the study. Of the 47 distant
      intracranial events, 34 occurred in isolation (i.e. only distant failure was
      identified), whilst 13 were accompanied by local failure. Data review showed
      compliance with the protocol mandated MRI schedule and accuracy of intracranial
      failure reporting was very high. The Quality of Life (QoL) component of the study
      achieved a 91% completion rate. For the neurocognitive function (NCF)
      assessments, a high completion rate was maintained throughout the 12 month
      period. Where assessments were not performed at expected time points, valid
      reasons were noted. Radiotherapy quality was high. Of 50 patients who received
      WBRT, 32 were reviewed as per protocol design and there was only one major
      variation out of 308 data points reviewed (0.3%). There were minimal trial
      related adverse events (AEs) and no serious adverse events (SAEs). Pre-specified
      protocol stopping rules were not met. CONCLUSIONS: The Data Safety Monitoring
      Committee (DSMC) recommended the trial continue recruitment after reviewing the
      unblinded data. The data provision and quality to date indicates that a reliable
      outcome will be obtained when the final analysis is performed. Accrual is ongoing
      with 156 out of 200 patients randomised to date (26(th) November 2014).

PMID- 25952980
TI  - Coordination Networks of a Ditopic Macrocycle Exhibiting Anion-Controlled
      Dimensional Changes and Crystal-to-Crystal Anion Exchange.
AB  - A rationally designed NO2S2-donor macrocycle L was synthesized, and anion
      variation (PF6(-), CF3CO2(-), NO3(-), and CF3SO3(-)) of its silver(I) complexes
      was employed as a strategy for controlling their coordination modes and network
      dimensions. The assembly reactions of L with four silver(I) salts afforded the
      complexes [Ag2L2](PF6)2 (1), [Ag4L2(CF3CO2)4]n (2), [Ag4L2(NO3)4]n (3), and
      {[Ag3L2(CF3SO3)2]CF3SO3}n (4) that adopt cyclic dimer, 1D, 2D, and pseudo 3D
      network structures, respectively, with the structure adopted depending on the
      coordination ability and coordination modes of the anion used. Interestingly,
      quantitative anion exchange accompanying an irreversible structural conversion
      from 2, 3, or 4 to 1 was observed in the crystalline state by powder X-ray
      diffraction (PXRD) and IR spectroscopy. A stepwise mechanistic process from 2
      (CF3CO2(-), 1D) to 3 (NO3(-), 2D) by anion exchange was also proposed. 

PMID- 25952981
TI  - Diaphragmatic crural augmentation utilising cross-linked porcine dermal collagen
      biologic mesh (Permacol) in the repair of large and complex para-oesophageal
      herniation: a retrospective cohort study.
AB  - OBJECTIVE: To evaluate the safety, efficacy and durability of selective
      integration of porcine dermal collagen (Permacol) biologic mesh for crural re
      construction in large or complex para-oesophageal hernia surgery. BACKGROUND:
      Surgical repair of para-oesophageal herniation has been associated with high
      rates of failure. The utilisation of prosthetic mesh is controversial with
      complications including erosion and fistulation. Long-term outcomes for biologic
      mesh crural augmentation are unclear. METHODS: A retrospective analysis of
      patients who underwent a biologic mesh (Permacol) augmented cruroplasty in the
      repair of large and/or complex para-oesophageal hernia was performed utilising
      the prospectively maintained oesophago-gastric database at the Royal Devon and
      Exeter Hospital between October 2004 and January 2013. This technique was
      selectively used for patients where the lateral extent of the diaphragmatic
      crural defect prevented the fashioning of a sound, tension-free repair with
      sutures alone, or previous surgery had failed. Successful outcome was defined by
      resolution of symptoms and structural integrity of the repair. RESULTS: Fifty one
      procedures were performed on 49 patients (15 male), median age 75 (range 25-91).
      Post-operative morbidity included 2 (3.9%) oesophageal injuries managed
      conservatively, and 2 (3.9%) patients who suffered early repair breakdown
      requiring immediate surgical re-intervention. Four patients (8%) required
      endoscopic dilatation due to dysphagia, one (2%) in the early post-operative
      phase. The median follow-up was 36 months (range 6-105). All patients reported
      initial symptomatic resolution. Two patients (4%) were demonstrated to have
      breakdown of their repair during the follow-up period, both of whom underwent
      revision mesh-augmented surgery and are re-incorporated in this series. Late
      onset dysphagia in two (4%) patients may be mesh-related, but no other
      complications were observed and a Kaplan-Meier analysis of this series predicts a
      symptom-free rate of approximately 94% at 5 years. CONCLUSIONS: The selective
      integration of biologic mesh to augment the crural repair in para-oesophageal
      hernia with extensive diaphragmatic defects appears to be safe, effective and
      infers the potential of long-term satisfactory outcomes.

PMID- 25952983
TI  - The "food waste challenge" can be solved.

PMID- 25952982
TI  - Efficacy of endoscopic mucosal resections for the management of small gastric
      adenomas with low-grade dysplasia.
AB  - OBJECTIVE: Gastric adenoma with low-grade dysplasia (LGD) can progress to gastric
      cancer; however, the optimal therapeutic modality for LGD has not been
      established. The aim of this study was to assess the efficacy, safety of and
      local recurrence following endoscopic mucosal resection (EMR) for LGD.
      Specifically, we compared EMR with circumferential precutting (EMR-P) and EMR
      using a dual-channel endoscope (EMR-D) for the treatment of LGD <=2 cm. MATERIALS
      AND METHODS: A total of 158 lesions from 147 patients with LGD treated by EMR
      were retrospectively analyzed. The en bloc resection rate, complete resection
      rate, procedure time, complication rate and local recurrence rate were compared
      between EMR-P and EMR-D. RESULTS: The en bloc resection and complete resection
      rates of EMR were 91.1% and 90.5%, respectively. The bleeding and perforation
      rates were 1.3% and 1.3%, respectively. The local recurrence rate following EMR
      was 2.2%. The en bloc resection and complete resection rates did not differ
      between EMR-P and EMR-D (88.2% vs. 92.5%, p = not significant (NS); and 90.2% vs.
      90.7%, p = NS, respectively). The procedure time was significantly longer for EMR
      P compared with EMR-D (16 (5-141) vs. 7 (2-48) min, p < 0.001), and the
      complication rate was significantly higher for EMR-P (7.8% vs. 0.0%, p = 0.010).
      Local recurrence was not found in EMR-P, whereas the recurrence rate was 3.2% in
      EMR-D. CONCLUSION: EMR is an effective method for the treatment of LGD <=2 cm.
      Compared with EMR-P, EMR-D appears to be the more effective, technically simple
      and safer method.

PMID- 25952984
TI  - Characterization of an extracellularly derived alpha-mannosidase from the liquid
      exudate of the sclerotia of Sclerotinia sclerotiorum (Lib.) de Bary.
AB  - Class I alpha-mannosidases play an important role in co- and post-translational N
      glycosylation modification of proteins, and also in glycoprotein glycan
      hydrolysis. Herein, we investigated a protein named Man-41, from liquid exudate
      droplets secreted on the surface of developing sclerotia by Sclerotinia
      sclerotiorum. The protein was identified by MALDI-TOF mass spectrometry to be a
      alpha-mannosidase. The full-length open reading frame of Man-41 consists of 1581
      bp, encoding 526 amino acid residues and containing a putative signal peptide at
      amino acid residues 1-20, and a conserved sequence at residues 50-521. Man-41 was
      classified into glycoside hydrolase family 47 (GH47) by clustering analysis. The
      catalytic residues include Glu(125), Arg(129), Asp(270), Ser(271), Glu(274),
      Arg(420), Glu(422), Glu(425), Glu(485), Thr(514), and Glu(515), which are
      conserved in all Class I alpha-1,2-mannosidases. Recombinant Man-41 protein had
      26.67 +/- 2.18 U/mg of alpha-mannosidase activity, about one-half of
      intracellular mannosidase activity of sclerotia. In conclusion, this is the first
      time that mannosidase has been identified in an extracellular fluid and Man-41 is
      also a new member of GH47 with Ca(2+)-dependent characteristics. This work lays
      the foundation for further study of the function of Man-41 in sclerotial
      development.

PMID- 25952985
TI  - Intervention strategies to eliminate truck-related fatalities in surface coal
      mining in West Virginia.
AB  - The main objective of this review was to build upon a previous study on the root
      causes of truck-related fatalities in surface coal mining operations in West
      Virginia, and to develop intervention strategies to eliminate these fatalities.
      This review considers a two-pronged approach to accident prevention: one that is
      fundamental and traditional (safety regulations, training and education, and
      engineering of the work environment); and one that is innovative and creative
      (e.g., applying technological advances to better control and eliminate the root
      causes of accidents). Suggestions for improving current training and education
      system are proposed, and recommendations are provided on improving the safety of
      mine working conditions, specifically safety conditions on haul roads, dump
      sites, and loading areas. We also discuss various currently available
      technologies that can help prevent haul truck-related fatal accidents. The
      results of this review should be used by mine personnel to help create safer
      working conditions and decrease truck-related fatalities in surface coal mining. 

PMID- 25952986
TI  - Reduced oxidative stress in primary human cells by antioxidant released from
      nanoporous alumina.
AB  - Nanoporous alumina elicits different inflammatory responses dependent on pore
      size, such as increased complement activation and reactive oxygen species (ROS)
      production, on 200 versus 20 nm pores. In this study, we attempt to further
      modulate inflammatory cell response by loading nanoporous alumina membranes (20,
      100, and 200 nm pores), with an antioxidant, Trolox, for controlled drug release.
      For mononuclear cells (MNC) no difference in cell response, due to pore size, was
      seen when cultured on nonloaded membranes. However, when exposed to membranes
      loaded with Trolox, 100 uM was enough to quench ROS by more than 95% for all pore
      sizes. Polymorphonuclear cells (PMNC) produced significantly more ROS when
      exposed to 20 versus 100 nm pores. For Trolox loaded membranes, this trend
      reversed, due to slower release of antioxidant from the 20 nm pores. Furthermore,
      Trolox exhibited a unique effect on PMNCs that has not previously been reported:
      It delayed the production of ROS in a manner distinct from antioxidant activity.
      The present study confirms that nanoporous alumina is a suitable vehicle for drug
      delivery, and that Trolox can successfully modulate the inflammatory response of
      both MNC and PMNCs.

PMID- 25952987
TI  - Deposition and depletion of decoquinate in eggs after administration of cross
      contaminated feed.
AB  - Decoquinate, a chemical coccidiostat used as a feed additive, can occur in eggs
      due to cross-contamination of feedstuffs for laying hens. An experiment was
      designed to assess the transfer of decoquinate to hen eggs and its distribution
      between egg yolk and egg white. Hens were given the feed containing decoquinate
      at a cross-contamination level (0.34 mg kg(-1)) and collected eggs were analysed
      using an LC-MS/MS method. The plateau level was reached on the eighth day of the
      experiment and averaged 8.91 ug kg(-1), which is far below the maximum level
      established at 20 ug kg(-1) for whole eggs. Decoquinate was deposited mostly in
      egg yolks (26.2 ug kg(-1)) and did not deplete completely during 14 days of
      administration of decoquinate-free feed. The results confirmed that
      administration of cross-contaminated feed is associated with very low risk of non
      compliant residue levels of decoquinate in eggs.

PMID- 25952988
TI  - Use of IV fosphenytoin pharmacokinetics to determine the loading dose for a
      clinical trial of canine status epilepticus.
AB  - OBJECTIVE: Canine status epilepticus (CSE) has potential as a translational
      platform to evaluate the safety and efficacy of novel compounds and inform human
      status epilepticus trials. The aim of this study was to determine the intravenous
      dose of fosphenytoin (FOS) needed for dogs in a CSE clinical trial to attain
      phenytoin (PHT) concentrations similar to those used for human status epilepticus
      and monitor PHT concentrations. METHODS: Four healthy dogs were used to
      characterize PHT pharmacokinetics. Each received either 15 mg/kg or 25 mg/kg of
      PHT equivalent intravenously. Blood samples were collected and FOS (total) and
      derived PHT (total and unbound) plasma concentrations were measured using high
      performance liquid chromatography-mass spectrometry (HPLC-MS). Noncompartmental
      pharmacokinetics (PK) parameter values were determined and compartmental PK
      modeling and simulations were used to select the dose for the clinical trial with
      a target goal of 1-2 MUg/ml unbound PHT at 30-60 min postinfusion. Predicted
      total and unbound PHT concentrations were compared with concentrations in blood
      collected from dogs treated for CSE in the clinical trial. RESULTS: Initial
      estimates suggested that a loading dose of 25 mg/kg would attain unbound
      concentrations of 1-2 MUg/ml; however, this dose produced concentrations above 3
      6 MUg/ml, which resulted in clinically significant toxicity. A two-compartment
      model best fit the PHT concentration data with alpha-phase half-life of 2-5 min
      and elimination half-life of ~5 h. Based on the simulations, a dose of 15 mg/kg
      was selected and used in the clinical trial and 15 of 16 dogs randomized to the
      treatment arm had PHT plasma concentrations within the goal range. SIGNIFICANCE:
      This study demonstrates that characterization of pharmacokinetics in a small
      number of dogs is useful in determining dosage regimens designed to attain
      targeted concentrations in clinical trials. Using this approach, we were able to
      determine a safe and effective dose of FOS for a clinical trial of CSE.

PMID- 25952990
TI  - Cyanide free contraction of disclosed 1,4-dioxane ring as a route to cobalt
      bis(dicarbollide) derivatives with short spacer between the boron cage and
      terminal functional group.
AB  - The 1,4-dioxane derivative of cobalt bis(dicarbollide) reacts with
      dialkylsulfides and triphenylphosphine to give the corresponding sulfonium and
      phosphonium derivatives [8-L(CH2CH2O)2-3,3'-Co(1,2-C2B9H10)(1',2'-C2B9H11)] (L =
      SMe2, S(CH2CH2)2O, PPh3). The treatment of the triphenylphosphonium derivative
      with sodium hydroxide results in contraction of the side chain with formation of
      [8-HOCH2CH2O-3,3'-Co(1,2-C2B9H10)(1',2'-C2B9H11)](-). The same product was
      obtained by treatment of the dimethylsulfonium derivative with the poorly
      nucleophilic base t-BuOK, whereas the stronger nucleophiles induce the sulfur
      demethylation to give [8-MeS(CH2CH2O)2-3,3'-Co(1,2-C2B9H10)(1',2'-C2B9H11)](-).
      The alcohol was used for the synthesis of a series of other short-spacer
      functional derivatives [8-XOCH2CH2O-3,3'-Co(1,2-C2B9H10)(1',2'-C2B9H11)](-) (X =
      NH2, SH, N3). A similar contraction of the disclosed 1,4-dioxane ring via the
      reactions with SMe2 and PPh3 can be used for the synthesis of short-spacer
      functional derivatives of nido-carborane, whereas the 1,4-dioxane derivatives of
      closo-decaborate and closo-dodecaborate anions, being stronger electron donors,
      are more stable and do not react with dimethylsulfide and triphenylphosphine. 

PMID- 25952991
TI  - Homokaryotic vs heterokaryotic mycelium in arbuscular mycorrhizal fungi:
      different techniques, different results?

PMID- 25952992
TI  - Steric considerations on improving the diastereomeric ratio of (+)- and (-)
      neomenthyl phenyl sulfoxides using bulky-headed oxidant
      hexadecyltrimethylammonium periodate and assignment of their configuration.
AB  - The bulky-headed oxidant hexadecyltrimethylammonium periodate affords the
      diastereomeric pairs, (Ss)-(+)/(Rs)-(+) and (Ss)-(-)/(Rs)-(-)-neomenthyl phenyl
      sulfoxides in stereochemically pure states with improved diastereomeric excess
      (48% diastereomeric excess [de]) as compared to its nonbulky counterpart, sodium
      metaperiodate (28% de) from respective (+)/(-)-neomenthyl phenyl sulfides. Steric
      effects involving the head group volume of hexadecyltrimethylammonium periodate
      is found to play a role in improving the diastereomeric ratio of the products.
      The two diastereomers can be readily separated by column chromatography. Absolute
      configuration at the sulfur center in (+)-neomenthyl phenyl sulfoxide was
      determined by single-crystal X-ray crystallography and found to be Ss. Relative
      configurations of other sulfoxides were assigned based on the configuration of
      (+)-neomenthyl phenyl sulfoxide.

PMID- 25952989
TI  - DISSECTING OCD CIRCUITS: FROM ANIMAL MODELS TO TARGETED TREATMENTS.
AB  - Obsessive-compulsive disorder (OCD) is a chronic, severe mental illness with up
      to 2-3% prevalence worldwide. In fact, OCD has been classified as one of the
      world's 10 leading causes of illness-related disability according to the World
      Health Organization, largely because of the chronic nature of disabling
      symptoms.([1]) Despite the severity and high prevalence of this chronic and
      disabling disorder, there is still relatively limited understanding of its
      pathophysiology. However, this is now rapidly changing due to development of
      powerful technologies that can be used to dissect the neural circuits underlying
      pathologic behaviors. In this article, we describe recent technical advances that
      have allowed neuroscientists to start identifying the circuits underlying complex
      repetitive behaviors using animal model systems. In addition, we review current
      surgical and stimulation-based treatments for OCD that target circuit
      dysfunction. Finally, we discuss how findings from animal models may be applied
      in the clinical arena to help inform and refine targeted brain stimulation-based
      treatment approaches. 

PMID- 25952993
TI  - TP53 mutation characteristics in therapy-related myelodysplastic syndromes and
      acute myeloid leukemia is similar to de novo diseases.
AB  - BACKGROUND: TP53 mutation is more prevalent in therapy-related myeloid neoplasms
      (t-MN) than their de novo counterparts; however, the pattern of mutations
      involving TP53 gene in t-MN versus de novo diseases is largely unknown. METHODS:
      We collected 108 consecutive patients with therapy-related myelodysplastic
      syndrome (t-MDS)/acute myeloid leukemia (t-AML). Clinical, hematological, and
      cytogenetic data were collected by searching the electronic medical record. TP53
      sequencing was performed in all patients using a clinically validated next
      generation sequencing-based gene panel assay. A previously published patient
      cohort consisting of 428 patients with de novo MDS/AML was included for
      comparison. RESULTS: We assessed 108 patients with t-MN, in which 40 patients
      (37%) had TP53 mutations. The mutation frequency was similar between t-MDS and t
      AML; but significantly higher than de novo MDS/AML (62/428 patients, 14.5%)
      (p<0.0001). TP53 mutations in t-MN were mainly clustered in DNA-binding domains,
      with an allelic frequency of 37.0% (range, 7.1 to 98.8). Most mutations involved
      single nucleotide changes, of which, transitions (65.9%) were more common than
      transversions (34.1%). Missense mutations were the most frequent, followed by
      frameshift and nonsense mutations. This TP53 mutation pattern was strikingly
      similar to that observed in de novo MDS/AML. TP53 mutations in t-MN were
      associated with a complex karyotype (p<0.0001), a higher number of chromosomal
      abnormalities (p<0.0001), and an inferior overall survival in affected patients
      (6.1 vs 14.1 months) by univariate (p<0.0001) and multivariate analyses
      (p=0.0020). CONCLUSIONS: Our findings support the recent notion that heterozygous
      TP53 mutation may be a function of normal aging and that mutated cells are
      subject to selection upon exposure to cytotoxic therapy. t-MN carrying TP53
      mutation have an aggressive clinical course independent of other confounding
      factors.

PMID- 25952994
TI  - An implication of relationship between tuberculosis and primary nephrotic
      syndrome.
AB  - PURPOSE: There have been few observations on the concurrence of tuberculosis (TB)
      and primary nephrotic syndrome (PNS). We try to define their relationship from
      multiple aspects. METHODS: Patients with PNS (n = 386), secondary nephrotic
      syndrome (SNS, n = 60), pneumonia (n = 196), and TB (n = 156) were enrolled.
      Through a novel evaluation system, the evidence of TB infection (clinical,
      laboratory, and radiographic evidence) was classified into 5 levels: lack of
      evidence (level 0), mild-to-moderate evidence (level 1-2), strong evidence (level
      3-4). Additionally, whether TB infection was primary or secondary to long-term
      steroid therapy for PNS was recorded. RESULTS: Through the evaluation system,
      42.24% (68/161) of PNS inpatients had evidence of TB level 1-4, more than those
      in SNS (23.33%, P = .788) or pneumonia (22.45%, P = .004); 9.32% (15/161) PNS
      inpatients had evidence of level 3-4, who should be considered as having TB; 13
      of the 15 patients had TB before the onset of PNS; 61.75%(96/153) PNS inpatients
      were abnormal on chest imaging. In the TB group, 28.21% (44/156) patients had
      abnormal urinalysis, more than those in the pneumonia group (8.16%, 16/196,
      P<0.001). TB-related symptoms were seldom seen in PNS inpatients (cough 26.1%,
      fever 6.8%; night sweats, fatigue, and weight loss were negative). CONCLUSIONS:
      Around 10% of PNS in children has an association with TB infection that preceded
      the onset of PNS.

PMID- 25952995
TI  - Time evolution of in vivo articular cartilage repair induced by bone marrow
      stimulation and scaffold implantation in rabbits.
AB  - PURPOSE: Tissue engineering techniques were used to study cartilage repair over a
      12-month period in a rabbit model. METHODS: A full-depth chondral defect along
      with subchondral bone injury were originated in the knee joint, where a biostable
      porous scaffold was implanted, synthesized of poly(ethyl acrylate-co-hydroxyethyl
      acrylate) copolymer. Morphological evolution of cartilage repair was studied 1
      and 2 weeks, and 1, 3, and 12 months after implantation by histological
      techniques. The 3-month group was chosen to compare cartilage repair to an
      additional group where scaffolds were preseeded with allogeneic chondrocytes
      before implantation, and also to controls, who underwent the same surgery
      procedure, with no scaffold implantation. RESULTS: Neotissue growth was first
      observed in the deepest scaffold pores 1 week after implantation, which spread
      thereafter; 3 months later scaffold pores were filled mostly with cartilaginous
      tissue in superficial and middle zones, and with bone tissue adjacent to
      subchondral bone. Simultaneously, native chondrocytes at the edges of the defect
      started to proliferate 1 week after implantation; within a month those edges had
      grown centripetally and seemed to embed the scaffold, and after 3 months, hyaline
      like cartilage was observed on the condylar surface. Preseeded scaffolds slightly
      improved tissue growth, although the quality of repair tissue was similar to non
      preseeded scaffolds. Controls showed that fibrous cartilage was mainly filling
      the repair area 3 months after surgery. In the 12-month group, articular
      cartilage resembled the untreated surface. CONCLUSIONS: Scaffolds guided
      cartilaginous tissue growth in vivo, suggesting their importance in stress
      transmission to the cells for cartilage repair.

PMID- 25952996
TI  - Therapeutic potential of umbilical cord mesenchymal stem cells in mice with acute
      hepatic failure.
AB  - BACKROUND/OBJECTIVE: Mesenchymal stem cells are probably one of the most
      promising alternatives for liver regeneration and repair. We present data
      supporting the ability of human umbilical cord mesenchymal stem cells (hUCMSCs)
      to generate hepatic elements and discuss the best transplantation pathway.
      METHODS: AHF mice were given hUCMSCs through tail-vein injection or into the
      liver lobes. Blood serum and liver tissues were collected to analyze the
      improvement of liver function and histological repair 24 h after hUCMSC
      administration. Real-time polymerase chain reaction and immunohistochemistry were
      used to detect the expression of human hepatocyte-specific markers in liver
      tissues. RESULTS: The results showed significant statistical differences in liver
      function after transplantation (P<.05). Real-time PCR and immunochemistry results
      demonstrated that the expression of hepatocyte-specific markers such as CK18 and
      AFP were obviously increased in the treatment groups through both transplantation
      pathways. Our data indicate that hUCMSCs are one of the stem cell candidates for
      liver repair because hUCMSCs can be easily and readily isolated and
      differentiated into hepatocytes both in vitro and in vivo. Additionally, tail
      vein injection of hUCMSCs has a similar therapeutic efficacy but is more
      convenient compared to liver lobe injection. CONCLUSIONS: Our findings highlight
      the potential therapeutic value of hUCMSCs and show that cell transplantation
      through a peripheral vein is a safe and effective way to treat AHF mice.
      Furthermore, this method might mediate repair in patients with liver damage or
      disease in future clinical therapy.

PMID- 25952997
TI  - Labeling and qualification of endothelial progenitor cells for tracking in tissue
      engineering: An in vitro study.
AB  - PURPOSE: In order to track location and distribution of endothelial cells (ECs)
      within scaffolds in vitro, we chose lentiPGK-TdTomato transduction of human
      endothelial progenitor cells (EPCs) isolated and differentiated from cord blood.
      Because transduction could have a functional impact on cell behavior, we checked
      different parameters for qualification of labeled- EPCs as well as their use for
      potential applications in the context of vascular and bone tissue engineering.
      METHODS: After isolation and expansion, EPCs were classically characterized then
      transduced with the lentiviral vector containing the TdTomato protein gene under
      the control of the phosphoglycerate kinase (PGK) promoter. Conventional
      karyotyping, differentiation capacity, viability, proliferation assays were
      performed with labeled and unlabeled EPCs. Scaffolds and co-cultures were
      explored with labeled EPCs, in static or shear stress conditions. RESULTS: Our
      results show that cell labeling did not affect cell adhesion nor induce cell
      death. Cell labeling did not induce more chromosomal aberrations. Phenotypical
      characterization was not affected. In the context of tissue engineering
      applications, labeled EPCs maintained their ability to line 2D or 3D scaffolds,
      withstand physiological arterial shear stress, and form tubular networks in co
      cultures with human osteoblast progenitor cells. CONCLUSIONS: It is possible to
      label human EPCs with TdTomato without affecting their behavior by the
      transduction procedure. This creates an important tool for numerous applications.
      Our results provide a qualification of labeled EPCs in comparison with unlabeled
      ones for vascular and bone tissue engineering.

PMID- 25952998
TI  - Binocular stereo-navigation for three-dimensional thoracoscopic lung resection.
AB  - BACKGROUND: This study investigated the efficacy of binocular stereo-navigation
      during three-dimensional (3-D) thoracoscopic sublobar resection (TSLR). METHODS:
      From July 2001, the authors' department began to use a virtual 3-D pulmonary
      model on a personal computer (PC) for preoperative simulation before
      thoracoscopic lung resection and for intraoperative navigation during operation.
      From 120 of 1-mm thin-sliced high-resolution computed tomography (HRCT)-scan
      images of tumor and hilum, homemade software CTTRY allowed sugeons to mark
      pulmonary arteries, veins, bronchi, and tumor on the HRCT images manually. The
      location and thickness of pulmonary vessels and bronchi were rendered as diverse
      size cylinders. With the resulting numerical data, a 3-D image was reconstructed
      by Metasequoia shareware. Subsequently, the data of reconstructed 3-D images were
      converted to Autodesk data, which appeared on a stereoscopic-vision display.
      Surgeons wearing 3-D polarized glasses performed 3-D TSLR. RESULTS: The patients
      consisted of 5 men and 5 women, ranging in age from 65 to 84 years. The clinical
      diagnoses were a primary lung cancer in 6 cases and a solitary metastatic lung
      tumor in 4 cases. Eight single segmentectomies, one bi-segmentectomy, and one bi
      subsegmentectomy were performed. Hilar lymphadenectomy with mediastinal lymph
      node sampling has been performed in 6 primary lung cancers, but four patients
      with metastatic lung tumors were performed without lymphadenectomy. The operation
      time and estimated blood loss ranged from 125 to 333 min and from 5 to 187 g,
      respectively. There were no intraoperative complications and no conversion to
      open thoracotomy and lobectomy. Postoperative courses of eight patients were
      uneventful, and another two patients had a prolonged lung air leak. The drainage
      duration and hospital stay ranged from 2 to 13 days and from 8 to 19 days,
      respectively. The tumor histology of primary lung cancer showed 5 adenocarcinoma
      and 1 squamous cell carcinoma. All primary lung cancers were at stage IA. The
      organs having metastatic pulmonary tumors were kidney, bladder, breast, and
      rectum. No patients had macroscopically positive surgical margins. CONCLUSIONS:
      Binocular stereo-navigation was able to identify the bronchovascular structures
      accurately and suitable to perform TSLR with a sufficient margin for small
      pulmonary tumors.

PMID- 25952999
TI  - Measurement of renal function in a kidney donor: a comparison of creatinine-based
      and volume-based GFRs.
AB  - OBJECTIVE: We aimed to evaluate the performance of various GFR estimates compared
      with direct measurement of GFR (dGFR). We also sought to create a new formula for
      volume-based GFR (new-vGFR) using kidney volume determined by CT. MATERIALS AND
      METHODS: GFR was measured using creatinine-based methods (MDRD, the Cockcroft
      Gault equation, CKD-EPI formula, and the Mayo clinic formula) and the Herts
      method, which is volume-based (vGFR). We compared performance between GFR
      estimates and created a new vGFR model by multiple linear regression analysis.
      RESULTS: Among the creatinine-based GFR estimates, the MDRD and C-G equations
      were similarly associated with dGFR (correlation and concordance coefficients of
      0.359 and 0.369 and 0.354 and 0.318, respectively). We developed the following
      new kidney volume-based GFR formula: 217.48-0.39XA + 0.25XW-0.46XH-54.01XsCr +
      0.02XV-19.89 (if female) (A = age, W = weight, H = height, sCr = serum creatinine
      level, V = total kidney volume). The MDRD and CKD-EPI had relatively better
      accuracy than the other creatinine-based methods (30.7% vs. 32.3% within 10% and
      78.0% vs. 73.0% within 30%, respectively). However, the new-vGFR formula had the
      most accurate results among all of the analyzed methods (37.4% within 10% and
      84.6% within 30%). CONCLUSIONS: The new-vGFR can replace dGFR or creatinine-based
      GFR for assessing kidney function in donors and healthy individuals. KEY POINTS:
      * Accurate prediction of GFR is crucial in kidney donors. * DTPA is accurate but
      costly, invasive, and clinically difficult to apply. * Volume-based GFR
      estimation performs as well as the Cr-based method. * New volume-based GFR
      estimation performs better among GFR estimation formulas.

PMID- 25953000
TI  - Lung cancer risk and cancer-specific mortality in subjects undergoing routine
      imaging test when stratified with and without identified lung nodule on imaging
      study.
AB  - OBJECTIVES: To assess the risk of lung cancer and specific mortality rate in
      patients with and without solitary pulmonary nodules (SPN) on chest radiograph
      and CT. METHODS: This prospective study included 16,078 patients >=35 years old
      (893 of them had an SPN detected with either chest radiograph or CT) and 15,185
      without SPN. Patients were followed up for 18 months or until being diagnosed
      with lung cancer. Risk and mortality lung cancer were calculated in both groups
      with Poisson regression. RESULTS: In patients with SPN, incidence of lung cancer
      was 8.3 % (95 % CI 6.0-11.2) on radiograph and 12.4 % (95 % CI 9.3-15.9) on CT. A
      chronic obstructive pulmonary disease in patients with radiographs (odds ratio
      2.62; 95 % CI 1.03, 6.67) and smoking habit (odds ratio 20.63; 95 % CI 3.84,
      110.77) in patients with CT were associated with a higher probability of lung
      cancer. Large nodule size and spiculated edge were associated with lung cancer on
      both CT and radiograph. Lung cancer-specific mortality was lower in patients with
      SPN than in those without SPN (1.73/1000 person-years, 95 % CI 1.08-2.88 vs.
      2.15/1000 person-years, 95 % CI 1.25-3.96). CONCLUSIONS: The risk of lung cancer
      for patients with SPN is higher in clinical populations than in screening
      studies. Moreover, patients with SPN showed lower mortality than those without
      SPN. KEY POINTS: * Lung cancer risk is 8 % for SPN detected on routine
      radiographs. * Lung cancer risk is 12.4 % for SPN detected in routine chest CT. *
      Smoking, COPD, SPN diameter and edge were predictors of malignancy. * Lung cancer
      risk of SPN in routine practice seems higher than in screening.

PMID- 25953003
TI  - Virulence assay of rhizoid and non-rhizoid morphotypes of Flavobacterium
      columnare in red tilapia, Oreochromis sp., fry.
AB  - Numerous isolates of Flavobacterium columnare were previously recovered from red
      tilapia, Oreochromis sp., exhibiting columnaris-like disease in Thai farms, and
      the phenotypic and genetic characteristics were described. The objective of this
      study was to determine the virulence of two morphotypes (rhizoid and non-rhizoid
      colonies) of F. columnare and to determine their ability to adhere to and persist
      in red tilapia fry. The results showed that the typical rhizoid isolate
      (CUVET1214) was a highly virulent isolate and caused 100% mortality within 24 h
      following bath challenge of red tilapia with three different doses. The non
      rhizoid isolate (CUVET1201) was avirulent to red tilapia fry. Both morphotypes
      adhered to and persisted in tilapia similarly at 0.5 and 6 h post-challenge as
      determined by whole fish bacterial loads. At 24 and 48 h post-challenge, fry
      challenged with the rhizoid morphotype exhibited significantly higher bacterial
      loads than the non-rhizoid morphotype. The results suggested that an inability of
      the non-rhizoid morphotype to persist in tilapia fry may explain lack of
      virulence. 

PMID- 25953002
TI  - mTOR-inhibitor treatment of metastatic renal cell carcinoma: contribution of Choi
      and modified Choi criteria assessed in 2D or 3D to evaluate tumor response.
AB  - PURPOSE: To determine whether 2D or 3D Choi and modified Choi (mChoi) criteria
      could assess the efficacy of everolimus against metastatic renal cell carcinoma
      (mRCC). METHODS: RECIST-1.1, Choi, and mChoi criteria were applied
      retrospectively to analyse baseline and 2-month contrast-enhanced computed
      tomography (CECT) images in 48 patients with mRCC enrolled in the everolimus arm
      of the French randomized double-blind multicentre phase III trial comparing
      everolimus versus placebo (RECORD-1). The primary endpoint was centrally reviewed
      progression-free survival (PFS) calculated from the initial RECORD-1 analysis.
      Mean attenuation was determined for 2D target lesion regions of interest drawn on
      CECT sections whose largest diameters had been measured, and for the 3D whole
      target lesion. RESULTS: The median PFS was 5.5 months. The median PFS for
      everolimus responders defined using 3D mChoi criteria was significantly longer
      than for non-responders (7.6 versus 5.4 months, respectively), corresponding to a
      hazard ratio for progression of 0.45 (95 % CI: 0.22-0.92), with respective 1-year
      survival rates of 31 % and 9 %. No other 2D or 3D imaging criteria at 2 months
      identified patients who would benefit from everolimus. CONCLUSIONS: At 2 months,
      only 3D mChoi criteria were able to identify mRCC patients with a PFS benefit
      from everolimus. KEY POINTS: Choi criteria could not identify everolimus-treated
      patients with significantly prolonged PFS. mCHOI enabled identification of
      everolimus-treated mRCC patients with a PFS benefit. 3D attenuation measurement
      criteria appeared to perform better than single-slice measurement.

PMID- 25953001
TI  - Impact of an intra-cycle motion correction algorithm on overall evaluability and
      diagnostic accuracy of computed tomography coronary angiography.
AB  - OBJECTIVES: The aim of this study was to evaluate the impact of a novel intra
      cycle motion correction algorithm (MCA) on overall evaluability and diagnostic
      accuracy of cardiac computed tomography coronary angiography (CCT). METHODS: From
      a cohort of 900 consecutive patients referred for CCT for suspected coronary
      artery disease (CAD), we enrolled 160 (18 %) patients (mean age 65.3 +/- 11.7
      years, 101 male) with at least one coronary segment classified as non-evaluable
      for motion artefacts. The CCT data sets were evaluated using a standard
      reconstruction algorithm (SRA) and MCA and compared in terms of subjective image
      quality, evaluability and diagnostic accuracy. RESULTS: The mean heart rate
      during the examination was 68.3 +/- 9.4 bpm. The MCA showed a higher Likert score
      (3.1 +/- 0.9 vs. 2.5 +/- 1.1, p < 0.001) and evaluability (94%vs.79 %, p < 0.001)
      than the SRA. In a 45-patient subgroup studied by clinically indicated invasive
      coronary angiography, specificity, positive predictive value and accuracy were
      higher in MCA vs. SRA in segment-based and vessel-based models, respectively
      (87%vs.73 %, 50%vs.34 %, 85%vs.73 %, p < 0.001 and 62%vs.28 %, 66%vs.51 % and
      75%vs.57 %, p < 0.001). In a patient-based model, MCA showed higher accuracy vs.
      SCA (93%vs.76 %, p < 0.05). CONCLUSIONS: MCA can significantly improve subjective
      image quality, overall evaluability and diagnostic accuracy of CCT. KEY POINTS:
      Cardiac computed tomographic coronary angiography (CCT) allows non-invasive
      evaluation of coronary arteries. Intra-cycle motion correction algorithm (MCA)
      allows for compensation of coronary motion. An MCA improves image quality, CCT
      evaluability and diagnostic accuracy.

PMID- 25953005
TI  - A central role for HSC70 in regulating antigen trafficking and MHC class II
      presentation.
AB  - Cells rely on multiple intracellular trafficking pathways to capture antigens for
      proteolysis. The resulting peptides bind to MHC class II molecules to promote
      CD4(+) T cell recognition. Endocytosis enhances the capture of extracellular and
      cell surface bound antigens for processing and presentation, while autophagy
      pathways shunt cytoplasmic and nuclear antigens for presentation in the context
      of MHC class II molecules. Understanding how physiological changes and cellular
      stress alter antigen trafficking and the repertoire of peptides presented by
      class II molecules remains challenging, yet important in devising novel
      approaches to boost immune responses to pathogens and tumors. An abundant,
      constitutively expressed cytoplasmic chaperone, HSC70 plays a central role in
      modulating antigen transport within cells to control MHC class II presentation
      during nutrient stress. HSC70 may serve as a molecular switch to modulate
      endocytic and autophagy pathways, impacting the source of antigens delivered for
      MHC class II presentation during cellular stress. 

PMID- 25953006
TI  - Spatially and temporally resolved gas distributions around heterogeneous
      catalysts using infrared planar laser-induced fluorescence.
AB  - Visualizing and measuring the gas distribution in close proximity to a working
      catalyst is crucial for understanding how the catalytic activity depends on the
      structure of the catalyst. However, existing methods are not able to fully
      determine the gas distribution during a catalytic process. Here we report on how
      the distribution of a gas during a catalytic reaction can be imaged in situ with
      high spatial (400 MUm) and temporal (15 MUs) resolution using infrared planar
      laser-induced fluorescence. The technique is demonstrated by monitoring, in real
      time, the distribution of carbon dioxide during catalytic oxidation of carbon
      monoxide above powder catalysts. Furthermore, we demonstrate the versatility and
      potential of the technique in catalysis research by providing a proof-of
      principle demonstration of how the activity of several catalysts can be measured
      simultaneously, either in the same reactor chamber, or in parallel, in different
      reactor tubes. 

PMID- 25953004
TI  - Patterns of Lipid Lowering Therapy among Children Ages 8-20 Years.
AB  - OBJECTIVES: Pediatric guidelines in 2008 and 2011 recommended lipid lowering
      therapy in children >= 8 years of age with high-risk cardiovascular conditions,
      such as familial hypercholesterolemia (FH). Our objective was to describe the
      patterns and predictors of lipid lowering therapy initiation in commercially
      insured children between 2005 and 2010. STUDY DESIGN: Using commercial health
      plan data on children ages 8-20 years from 2004-2010, we estimated rates of lipid
      lowering therapy initiation overall and stratified by age. Using a nested case
      control design, we used multivariable logistic regression to identify temporal,
      demographic, clinical, and health utilization characteristics associated with
      lipid lowering therapy initiation. RESULTS: Among >13 million children, 665
      initiated lipid lowering therapy for an incidence rate 2.6/100,000 person-years
      (PY). Incidence rates were highest in 2005 (4.1/100,000 PY) and 2008 (3.9/100,000
      PY), with no discernable secular trend. Rates of lipid lowering therapy
      initiation were significantly greater in children >= 15 years of age (OR 2.9 [95%
      CI 5.2-13.0]), males (2.1 [1.7-2.4]), and those with a diagnosis of FH (165.2
      [129.0-211.6]), other dyslipidemia (175.5 [143.2-215.3]), diabetes type I (7.7
      [4.7-12.4]), diabetes type II (13.6 [8.5-21.7]), hypertension (8.1 [4.9-13.3]),
      obesity (7.8 [4.7-12.7]), and >= 5 outpatient visits (1.5 [1.2-1.7]), and
      children with dispensing of >= 2 nonlipid lowering therapy prescriptions were
      less likely to initiate lipid lowering therapy (0.2 [0.2-0.3]). CONCLUSIONS:
      Despite new guidelines, lipid lowering therapy initiation in children is low and
      has not increased through 2010. Although diagnosis of FH and other dyslipidemias
      was associated with higher probability of lipid lowering therapy initiation, our
      findings suggest lipid lowering therapy is underutilized in this population given
      the prevalence of these disorders.

PMID- 25953007
TI  - Recurrent incisional hernia, enterocutaneous fistula and loss of the substance of
      the abdominal wall: plastic with organic prosthesis, skin graft and VAC therapy.
      Clinical case.
AB  - Surgical wounds dehiscence is a serious post-operatory complication, with an
      incidence between 0.4% and 3.5%. Mortality is more than 45%. Complex wounds
      treatment may require a multidisciplinary management. VAC Therapy could be an
      alternative treatment regarding complex wound. VAC therapy has been recently
      introduced on skin's graft tissue management reducing skin graft rejection. The
      use of biological prosthesis has been tested in a contaminated field, better than
      synthetic meshes, which often need to be removed. The Permacol is more resistant
      to degradation by proteases due to its cross-links. Surgery is still considered
      the best treatment for digestive fistula. A 58 years old obese woman come to our
      attention, she was operated for an abdominal hernia. She had a post-operatory
      entero-cutaneous fistula. She was submitted to bowel resection, the anastomosis
      has been tailored and the hernia of the abdominal wall has been repaired with
      biological mesh for managing such condition. She had a wound dehiscence with loss
      of substance and the exposure of the biological prosthesis, nearly 20 cm
      diameter. She was treated first with antibiotic therapy and simple medications.
      In addiction, antibiotic therapy was necessary late associated to 7 months with
      advanced medications allowed a small reduction's defect. Because of its,
      treatment went on for two more months using VAC therapy. Antibiotic's therapy was
      finally suspended. The VAC therapy allowed the reduction of the gap, between skin
      and subcutaneous tissue, and the defect's size preparing a suitable ground for
      the skin graft. The graft, managed with the vac therapy, was necessary to
      complete the healing process.

PMID- 25953008
TI  - The promises and limitations of gender-transformative health programming with
      men: critical reflections from the field.
AB  - Since the 1994 International Conference on Population and Development,
      researchers and practitioners have engaged in a series of efforts to shift health
      programming with men from being gender-neutral to being more gender-sensitive and
      gender-transformative. Efforts in this latter category have been increasingly
      utilised, particularly in the last decade, and attempt to transform gender
      relations to be more equitable in the name of improved health outcomes for both
      women and men. We begin by assessing the conceptual progression of social science
      contributions to gender-transformative health programming with men. Next, we
      briefly assess the empirical evidence from gender-transformative health
      interventions with men. Finally, we examine some of the challenges and
      limitations of gender-transformative health programmes and make recommendations
      for future work in this thriving interdisciplinary area of study. 

PMID- 25953009
TI  - Risk factors for work-related injury among farm workers: a 1-year study.
AB  - A 1-year prospective study was carried out to look for risk factors of farm
      related injuries in Egusquiza, Santa Fe (Argentina). Information on demographic
      characteristics and occupational accidents was collected on (<i>N</i>=110,
      <i>n</i>=78) farm workers by means of personal interviews using a structured
      questionnaire. Monthly telephone contact was then maintained with the workers for
      1 year to document all farm-related injuries. Data analysis included incidence
      rate, &#967;2 and logistic regression. Sixty-nine farm-related injuries were
      reported during the study period, six injuries being the maximum number affecting
      one worker. A total of 46.3% of the workers suffered at least one injury during
      the year. The incidence rate was 7.5 injuries/100 individual-month at risk.
      Medical assistance was needed in 26.8% of the cases and 5.8% of the injuries
      caused at least 1 day off work. Hospitalization for at least 1 day was required
      for 2.9% of the injured workers. Previous work-related injury in the family
      (<i>p</i>=0.005) (odds ratio (OR)=4.6, 95% confidence interval (CI)=1.6-13.3) and
      worker's activity (<i>p</i>=0.021) (OR=3.7, 95%CI=1.2-11.6) were associated with
      the dependent variable work injury. Agricultural and livestock farming are of
      great importance for the national economy. Workers' training on farm safety may
      play a key role to prevent work-related injuries and diseases. 

PMID- 25953010
TI  - Establishing a volunteer doula program within a nurse-midwifery education
      program: a winning situation for both clients and students.
AB  - The use of labor doulas is beneficial for mothers and newborns, but availability
      and cost can be barriers. The Nashville Volunteer Doula Program was formed to
      provide labor support to clients of a faculty nurse-midwifery practice. The
      volunteer doula pool is comprised of both nurse-midwifery students who have
      trained as doulas and community doulas. Training and coordination of volunteers
      are managed by nurse-midwifery students with faculty support. Students gain
      valuable exposure to providing supportive care during labor and birth, which
      augments their nurse-midwifery education. This novel program operates at a low
      cost and offers benefits to students as well as women who use the doula service.
      This article is part of a special series of articles that address midwifery
      innovations in clinical practice, education, interprofessional collaboration,
      health policy, and global health. 

PMID- 25953012
TI  - The best clinical paper on multiple sclerosis in 2014.

PMID- 25953011
TI  - Microfluidic Chip for Site-Specific Neuropharmacological Treatment and Activity
      Probing of 3D Neuronal "Optonet" Cultures.
AB  - The study introduces a "brain-on-a-chip" microfluidic platform that hosts brain
      like 3D cultures ("optonets") whose activity and responses to flowing drugs are
      recorded optically. Optonets are viable, optically accessible 3D neural networks
      whose characteristics approximate cortical networks. The results demonstrate the
      ability to monitor complex 3D activity patterns during extended site-specific,
      reversible neuropharmacogical exposure, suggesting an interesting potential in
      drug screening. 

PMID- 25953013
TI  - The impact of endovascular repair on specialties performing abdominal aortic
      aneurysm repair.
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) repair has been performed by various
      surgical specialties for many years. Endovascular aneurysm repair (EVAR) may be a
      disruptive technology, having an impact on which specialties care for patients
      with AAA. Therefore, we examined the proportion of AAA repairs performed by
      various specialties over time in the United States and evaluated the impact of
      the introduction of EVAR. METHODS: The Nationwide Inpatient Sample (2001-2009)
      was queried for intact and ruptured AAA and for open repair and EVAR. Specific
      procedures were used to identify vascular surgeons (VSs), cardiac surgeons (CSs),
      and general surgeons (GSs) as well as interventional cardiologists and
      interventional radiologists for states that reported unique treating physician
      identifiers. Annual procedure volumes were subsequently calculated for each
      specialty. RESULTS: We identified 108,587 EVARs and 85,080 open AAA repairs (3011
      EVARs and 12,811 open repairs for ruptured AAA). VSs performed an increasing
      proportion of AAA repairs during the study period (52% in 2001 to 66% in 2009; P
      < .001). GSs and CSs performed fewer repairs during the same period (25% to 17%
      [P < .001] and 19% to 13% [P < .001], respectively). EVAR was increasingly used
      for intact (33% to 78% of annual cases; P < .001) as well as ruptured AAA repair
      (5% to 28%; P < .001). The proportion of intact open repairs performed by VSs
      increased from 52% to 65% (P < .001), whereas for EVAR, the proportion went from
      60% to 67% (P < .001). The proportion performed by VSs increased for ruptured
      open repairs from 37% to 53% (P < .001) and for ruptured EVARs from 28% to 73% (P
      < .001). Compared with treatment by VSs, treatment by a CS (0.55 [0.53-0.56]) and
      GS (0.66 [0.64-0.68]) was associated with a decreased likelihood of undergoing
      endovascular rather than open AAA repair. CONCLUSIONS: VSs are performing an
      increasing majority of AAA repairs, in large part driven by the increased
      utilization of EVAR for both intact and ruptured AAA repair. However, GSs and CSs
      still perform AAA repair. Further studies should examine the implications of
      these national trends on the outcome of AAA repair.

PMID- 25953014
TI  - Prediction of in-hospital mortality after ruptured abdominal aortic aneurysm
      repair using an artificial neural network.
AB  - OBJECTIVE: Ruptured abdominal aortic aneurysm (rAAA) carries a high mortality
      rate, even with prompt transfer to a medical center. An artificial neural network
      (ANN) is a computational model that improves predictive ability through pattern
      recognition while continually adapting to new input data. The goal of this study
      was to effectively use ANN modeling to provide vascular surgeons a discriminant
      adjunct to assess the likelihood of in-hospital mortality on a pending rAAA
      admission using easily obtainable patient information from the field. METHODS: Of
      332 total patients from a single institution from 1998 to 2013 who had attempted
      rAAA repair, 125 were reviewed for preoperative factors associated with in
      hospital mortality; 108 patients received an open operation, and 17 patients
      received endovascular repair. Five variables were found significant on
      multivariate analysis (P < .05), and four of these five (preoperative shock, loss
      of consciousness, cardiac arrest, and age) were modeled by multiple logistic
      regression and an ANN. These predictive models were compared against the Glasgow
      Aneurysm Score. All models were assessed by generation of receiver operating
      characteristic curves and actual vs predicted outcomes plots, with area under the
      curve and Pearson r(2) value as the primary measures of discriminant ability.
      RESULTS: Of the 125 patients, 53 (42%) did not survive to discharge. Five
      preoperative factors were significant (P < .05) independent predictors of in
      hospital mortality in multivariate analysis: advanced age, renal disease, loss of
      consciousness, cardiac arrest, and shock, although renal disease was excluded
      from the models. The sequential accumulation of zero to four of these risk
      factors progressively increased overall mortality rate, from 11% to 16% to 44% to
      76% to 89% (age >= 70 years considered a risk factor). Algorithms derived from
      multiple logistic regression, ANN, and Glasgow Aneurysm Score models generated
      area under the curve values of 0.85 +/- 0.04, 0.88 +/- 0.04 (training set), and
      0.77 +/- 0.06 and Pearson r(2) values of .36, .52 and .17, respectively. The ANN
      model represented the most discriminant of the three. CONCLUSIONS: An ANN-based
      predictive model may represent a simple, useful, and highly discriminant adjunct
      to the vascular surgeon in accurately identifying those patients who may carry a
      high mortality risk from attempted repair of rAAA, using only easily definable
      preoperative variables. Although still requiring external validation, our model
      is available for demonstration at
      https://redcap.vanderbilt.edu/surveys/?s=NN97NM7DTK.

PMID- 25953016
TI  - Prospective multicenter study with a 1-year analysis of a new vascular graft used
      for early cannulation in patients undergoing hemodialysis.
AB  - OBJECTIVE: More than 85% of patients with end-stage renal disease start dialysis
      through a tunneled dialysis catheter (TDC) for long periods while their
      arteriovenous fistula or vascular access graft (arteriovenous graft [AVG])
      matures. Because TDCs are associated with a high risk of complications, including
      death and infection, use of an AVG that can be cannulated safely immediately
      after implantation may reduce morbidity in these patients by allowing earlier TDC
      removal. We report a prospective multicenter study of a new early-cannulation AVG
      (Gore ACUSEAL Vascular Graft; W. L. Gore & Associates, Flagstaff, Ariz). METHODS:
      Patients requiring creation of a prosthetic vascular access for hemodialysis were
      enrolled between July 2010 and February 2012 and observed for 12 months. Data
      were collected on the patients' baseline characteristics; location, position,
      loss of patency, and revisions of prior AVGs; dialysis sessions using the AVG;
      and major adverse events related to graft implantation or cannulation. Cumulative
      and primary unassisted graft patency rates were calculated. A subgroup analysis
      compared outcomes in patients in whom the AVG was first cannulated within 72
      hours after implantation with outcomes in patients in whom the initial
      cannulation was performed >21 days postoperatively. RESULTS: The population of
      this study was formed by 138 patients who received an ACUSEAL graft. During
      follow-up, 17 patients died and the AVG was abandoned in 27. The median value for
      follow-up was 360 days for all patients (variance 15,387). The overall mean time
      to initial cannulation was 15 days, with 54 grafts (40%) first cannulated within
      72 hours after graft implantation and 33 grafts first cannulated >21 days
      afterward. The reason for late cannulation in some patients was dependent on the
      implanting surgeon's decision and the surgeon's personal experience with early
      cannulating grafts. The 1-year overall cumulative patency rate was 79% (95%
      confidence interval, 71%-85%); the primary unassisted patency rate was 35% (95%
      confidence interval, 27%-44%). Adverse events included 6 hematomas (two of which
      were related to cannulation and occurred 107 and 169 days, respectively, after
      AVG implantation), 15 graft infections, and 15 cases of steal syndrome requiring
      intervention. Patients in the early- and later-cannulation groups had similar
      characteristics and no significant differences in rates of cumulative or primary
      unassisted patency or adverse events. CONCLUSIONS: This study demonstrated that
      the new, early-cannulation AVG graft can be cannulated soon after implantation
      without a significant difference in patency and complication rates compared with
      rates associated with standard cannulation of expanded polytetrafluoroethylene
      grafts in the literature. This new AVG may allow early removal or avoidance of
      TDC use in patients undergoing hemodialysis, potentially reducing or eliminating
      the number of days of catheter-dependent dialysis, but further studies will be
      needed to demonstrate this potential.

PMID- 25953015
TI  - Outcomes of infrainguinal bypass determined by age in the Vascular Study Group of
      New England.
AB  - BACKGROUND: Many believe extremes of age correlate with poorer outcomes in
      treatment for lower extremity peripheral arterial disease (PAD). We hypothesized
      that the youngest patients would have significantly poorer outcomes compared with
      older cohorts due to the precocious nature of their PAD. METHODS: We studied all
      patients in the Vascular Study Group of New England database undergoing
      infrainguinal bypass for PAD between 2003 and 2013. Age was grouped by <50 years,
      50 to 79 years, and >=80 years. Our primary outcomes were 1-year freedom from a
      major adverse limb event (MALE), defined as ipsilateral amputation or need for
      secondary intervention, and amputation-free survival. A second analysis was
      performed to analyze the subgroup of patients aged <50 years with critical limb
      ischemia (CLI), which included a Cox regression model to determine risk factors
      for MALE or death at 1 year. RESULTS: Of 5265 patients who were treated with
      infrainguinal bypass for PAD, 324 (6.2%) were aged <50 years. The mean age was
      44.6 years, and 66.4% were male. The proportion of African Americans was
      significantly higher in the youngest age group (<50 years: 6.8% vs 50-79 years:
      3.5%, P = .002; vs >=80 years: 3.5%, P = .013). More bypasses were done for
      claudication than acute limb ischemia in patients aged <50 years (33.3% vs
      11.4%). More vein grafts were used vs prosthetic (<50 years: 72.1% vs 50-79
      years: 65.9%, P = .024; vs >=80 years: 62.6%, P = .002). Fewer concomitant
      proximal procedures were performed compared with the older groups (<50 years:
      37.7% vs 50-79 years: 51.1%, P < .001; vs >=80 years: 39.5%, P = .045). More
      young patients returned to the operating room within their initial
      hospitalization for early graft thrombosis (<50 years: 5.6% vs 50-79 years: 2.9%,
      P = .001; vs >=80 years: 2.4%, P = .009) and revision (<50 years: 4.7% vs 50-79
      years: 2.2%, P = .012; vs >=80 years: 1.4%, P = .002) compared with the older
      patients. Overall, MALE-free survival was similar across age groups (P = .323),
      as were patency and amputation rates. When considering only patients with CLI,
      MALE-free survival in the youngest patients was again similar (P = .171) but with
      significantly more major amputations at 1 year (P = .022). CONCLUSIONS: For
      patients aged <50 undergoing infrainguinal bypass surgery, this large series
      demonstrates similar overall medium-term graft-related outcomes compared with
      older cohorts. Further, although the youngest patients with CLI have similar
      MALEs, their amputation rates are higher than in older cohorts.

PMID- 25953017
TI  - Multicenter Nellix EndoVascular Aneurysm Sealing system experience in aneurysm
      sac sealing.
AB  - OBJECTIVE: Despite improvements in endograft devices, operator technique, and
      patient selection, endovascular repair has not achieved the long-term durability
      of open surgical aneurysm repair. Persistent or recurrent aneurysm sac flow from
      failed proximal sealing, component failure, or branch vessel flow underpins a
      significant rate of reintervention after endovascular repair. The Nellix device
      (Endologix, Irvine, Calif) employs a unique design with deployment of polymer
      filled EndoBags surrounding the endograft flow lumens, sealing the aneurysm sac
      space and potentially reducing complications from persistent sac flow. This
      retrospective analysis represents the initial experience in consecutive patients
      treated with the device in real-world practice. METHODS: This study was performed
      at six clinical centers in Europe and one in New Zealand during the initial
      period after commercialization of the Nellix device. Patients underwent
      evaluation with computed tomography and other imaging modalities following local
      standards of care. Patients were selected for treatment with Nellix and treated
      by each institution according to its endovascular repair protocol. Clinical and
      imaging end points included technical success (successful device deployment and
      absence of any endoleak at completion angiography), freedom from all-cause and
      aneurysm-related mortality, endoleak by type, limb occlusion, aneurysm rupture,
      and reintervention. RESULTS: During a 17-month period, 171 patients with
      abdominal aortic aneurysms were treated with the Nellix device and observed for a
      median of 5 months (range, 0-14 months). The 153 male and 18 female patients with
      mean age of 74 +/- 7 years had aneurysms 61 +/- 9 mm in diameter with an average
      infrarenal neck length of 28 +/- 15 mm and infrarenal angulation of 37 +/- 22
      degrees. Technical success was achieved in all but two patients (99%); one
      patient had a type Ib endoleak and another had a type II endoleak. Through the
      last available follow-up, type Ia endoleak was observed in five patients (3%),
      type Ib endoleak in four patients (2%), and type II endoleak in four patients
      (2%). There were eight limb occlusions (5%), among which seven were evident at
      the 1-month follow-up visit. Aneurysm-related reinterventions were performed in
      15 patients (9%). There were no aneurysm ruptures or open surgical conversions.
      CONCLUSIONS: This first multicenter postmarket report of the Nellix device for
      infrarenal abdominal aortic aneurysm repair demonstrates satisfactory results
      during the initial learning phase of this new technology. The rate of aneurysm
      exclusion was high, and frequency of complications was low. More definitive
      conclusions on the value of this novel device await the results of the ongoing
      Nellix EVAS FORWARD Global Registry and the EVAS FORWARD investigational device
      exemption trial.

PMID- 25953018
TI  - Technical risk factors for portal vein reconstruction thrombosis in pancreatic
      resection.
AB  - OBJECTIVE: Vascular reconstruction can facilitate pancreas tumor resection, but
      optimal methods of reconstruction are not well studied. We report our results for
      portal vein reconstruction (PVR) for pancreatic resection and determinants of
      postoperative patency. METHODS: We identified 173 patients with PVR in a
      prospective database of 6522 patients who underwent pancreatic resection at our
      hospital from 1970 to 2014. There were 128 patients who had >1 year of follow-up
      with computed tomography imaging. Preoperative, intraoperative, and postoperative
      factors were recorded. Patients with and without postoperative PVR thrombosis
      were compared by univariable, multivariable, and receiver operating
      characteristic curve analyses. RESULTS: The survival of patients was 100% at 1
      month, 88% at 6 months, 66% at 1 year, and 39% on overall median follow-up of 310
      days (interquartile range, 417 days). Median survival was 15.5 months
      (interquartile range, 25 months); 86% of resections were for cancer. Four types
      of PVR techniques were used: 83% of PVRs were performed by primary repair, 8.7%
      with interposition vein graft, 4.7% with interposition prosthetic graft, and 4.7%
      with patch. PVR patency was 100% at 1 day, 98% at 1 month, 91% at 6 months, and
      83% at 1 year. Patients with PVR thrombosis were not significantly different from
      patients with patent PVR in age, survival, preoperative comorbidities, tumor
      characteristics, perioperative blood loss or transfusion, or postoperative
      complications. They were more likely to have had preoperative chemotherapy (53%
      vs 9%; P < .0001), radiation therapy (35% vs 2%; P < .0001), and prolonged
      operative time (618 +/- 57 vs 424 +/- 20 minutes; P = .002) and to develop
      postoperative ascites (76% vs 22%; P < .001). Among patients who developed
      ascites, 38% of those with PVR thrombosis did so in the setting of tumor
      recurrence at the porta detected on imaging, whereas among patients with patent
      PVR, 50% did so (P = .73). Patients with PVR thrombosis were more likely to have
      had prosthetic graft placement compared with patients with patent PVRs (18% vs
      2.7%; P = .03; odds ratio [OR], 7.7; 95% confidence interval [CI], 1.4-42). PVR
      patency overall was significantly worse for patients who had an interposition
      prosthetic graft reconstruction (log-rank, P = .04). On multivariable analysis,
      operative time (OR, 1.01; 95% CI, 1.01-1.02) and prosthetic graft placement (OR,
      8.12; 95% CI, 1.1-74) were independent predictors of PVR thrombosis (C statistic
      = 0.88). CONCLUSIONS: Long operative times and use of prosthetic grafts for
      reconstruction are risk factors for postoperative portal vein thrombosis. Primary
      repair, patch, or vein interposition should be preferentially used for PVR in the
      setting of pancreatic resection.

PMID- 25953019
TI  - Outcomes of the single-stent versus kissing-stents technique in asymmetric
      complex aortoiliac bifurcation lesions.
AB  - OBJECTIVE: This study investigated the outcomes of single-stent vs kissing-stents
      techniques in asymmetric complex aortoiliac bifurcation (ACAB) lesions. METHODS:
      We retrospectively investigated 80 consecutive patients (69 males, 66.6 +/- 8.7
      years) treated with a single stent and 30 patients (26 males, 67.1 +/- 7.7 years)
      treated with kissing stents for ACAB between January 2005 and December 2012 from
      a single-center cohort. A ACAB lesion was defined as a symptomatic unilateral
      common iliac artery stenosis (>50%) combined with intermediate stenosis (30%-50%)
      in the contralateral common iliac artery ostium. The primary end point was the
      primary patency of the ACAB. RESULTS: The baseline clinical characteristics did
      not differ significantly between the single-stent and the kissing-stents group.
      Technical success was achieved in all patients. The single-stent group required
      fewer stents (1.3 +/- 0.5 vs 2.3 +/- 0.8; P < .001) and less bilateral femoral
      access (55% vs 100%; P < .001). Two patients in the single-stent group (3%)
      required bailout kissing stents because of plaque shift to the contralateral
      side. The major complication rates were 8% in single-stent vs 13% in the kissing
      stent group, which was similar (P = .399). At 3 years, the single-stent and
      kissing-stents group had similar rates of primary patency (89% vs 87%; P = .916)
      and target lesion revascularization-free survival (93% vs 87%; P = .462).
      CONCLUSIONS: The single-stent technique in ACAB was safe and showed midterm
      outcomes comparable with those of kissing stents. Considering the benefits, such
      as fewer stents, less bilateral femoral access, and the availability of
      contralateral access for future intervention, the single-stent technique may be
      an advantageous treatment option in ACAB.

PMID- 25953020
TI  - Ultrasound-guided regional anesthesia for carotid endarterectomy induces early
      hemodynamic and stress hormone changes.
AB  - OBJECTIVE: Locoregional anesthesia is an effective method for evaluating cerebral
      function during carotid endarterectomy (CEA). Landmark-guided regional anesthesia
      (RA) is currently used for CEA and can provoke substantial perioperative
      hypertension. Ultrasound-guided RA (US-RA) is a new method for performing RA in
      CEA; however, the effect on sympathetic activity and blood pressure is uncertain.
      This study assessed early sympathetic activity during CEA in US-RA compared with
      general anesthesia (GA). METHODS: Patients were prospectively randomized to
      receive US-RA (n = 32) or GA (n = 28) for CEA. The primary end point was the
      change in systolic arterial blood pressure after induction of anesthesia (just
      before starting surgery) comparing US-RA with GA. We also recorded heart rate and
      analyzed concentrations of plasma blood hormones, including cortisol,
      metanephrine, and normetanephrine at five different times. Creatinine kinase,
      troponin I, and N-terminal pro-B-type natriuretic peptide were analyzed to detect
      potential changes in cardiac biomarkers during the procedure. RESULTS: Systolic
      arterial blood pressure (mean +/- standard deviation) increased significantly in
      US-RA patients compared with GA patients even before surgery was initiated (180
      +/- 26 mm Hg vs 109 +/- 24 mm Hg; P < .001), then remained elevated during the
      entire surgery and returned to baseline values 1 hour after admission to the
      postoperative anesthesia care unit. Heart rate (US-RA: 78 +/- 16 beats/min, GA:
      52 +/- 12 beats/min; P < .001) and cortisol levels (US-RA: 155 +/- 97 MUg/L, GA:
      99 +/- 43 MUg/L; P = .006) were also significantly higher in the US-RA group
      after induction of anesthesia. Other values did not differ. CONCLUSIONS: The US
      RA technique for CEA induces temporary intraoperative hypertension and an
      increase in stress hormone levels. Nevertheless, US-RA is a feasible, effective,
      and safe form of locoregional for CEA that enables targeted placement of low
      volumes of local anesthesia under direct visualization.

PMID- 25953021
TI  - Outcomes of completion imaging for lower extremity bypass in the Vascular Quality
      Initiative.
AB  - OBJECTIVE: The objective of this study was to determine the association of
      intraoperative completion imaging (CI) for lower extremity vein bypass to a below
      knee target with primary patency in the Vascular Quality Initiative. METHODS: The
      Vascular Quality Initiative database was queried from January 2003 to October
      2013 for lower extremity bypass (LEB) procedures that were elective, had an
      indication of occlusive disease, used a single-segment greater saphenous vein
      conduit, and had a below-knee target. LEBs with inflow arteries above the knee
      and below the knee were included. LEBs with concomitant endovascular procedures
      were excluded. CI was defined as completion angiography, completion duplex
      ultrasound, or both. The end points were primary patency at discharge and at 1
      year. Multivariable analysis was performed controlling for patient demographics,
      comorbidities, bypass characteristics, and center. RESULTS: Of 14,284 LEBs that
      were performed during the study period, 3147 satisfied the inclusion and
      exclusion criteria. Of 1457 (46%) that underwent CI, 287 (20%) underwent duplex
      ultrasound, 1116 (77%) underwent angiography, and 54 (3.7%) underwent both duplex
      ultrasound and angiography. There were more patients in the CI group with a
      history of smoking and a bypass graft crossing the knee. There was no difference
      in primary patency at discharge between the two groups (CI, 93.2% vs no CI,
      93.8%; P = .52). Of the patients who underwent CI, the discharge primary patency
      was 95.1% for completion duplex ultrasound vs 92.8% for completion angiography (P
      = .17). On multivariable analysis, there was no significant association of CI
      with discharge primary patency (P = .69). The 1-year primary patency was 63% in
      the CI group vs 68% in the no CI group (P = .051). The 1-year primary patency was
      60% for the duplex ultrasound group vs 65% for the angiography group (P = .61).
      On multivariable analysis, there was no significant association of CI with 1-year
      primary patency (P = .69). CONCLUSIONS: In electively performed LEBs using single
      segment saphenous vein to a below-knee target artery for occlusive disease, CI
      does not influence primary graft patency at discharge or at 1 year.

PMID- 25953022
TI  - Dynamic muscle quality of the plantar flexors is impaired in claudicant patients
      with peripheral arterial disease and associated with poorer walking endurance.
AB  - OBJECTIVE: Peripheral arterial disease and intermittent claudication (PAD-IC)
      negatively affects physical activity and function. There is evidence for
      plantarflexor muscle dysfunction and weakness; however, the extent to which this
      dysfunction can be attributed to reduced muscle size or quality, or both, is not
      yet known. This study investigated whether in vivo plantarflexor muscle quality
      during static and dynamic contractions is altered by PAD-IC and whether such
      changes are associated with impaired walking endurance according to initial and
      absolute claudication distances. METHODS: The study recruited 22 participants,
      consisting of 10 healthy controls and 12 claudicant patients with occlusion of
      the superficial femoral artery (seven unilateral and five bilateral). Muscle
      quality of the combined gastrocnemius muscles during static contractions was
      calculated by normalizing the estimated maximal potential muscle force to the
      physiological cross-sectional area of the lateral and medial gastrocnemius.
      Muscle quality during dynamic contractions of the combined plantarflexor muscles
      was calculated as the ratio of peak voluntary concentric plantarflexor power and
      the summed volume of lateral and medial gastrocnemius. RESULTS: Dynamic muscle
      quality was 24% lower in the claudicating-limb and asymptomatic-limb groups
      compared with controls (P = .017 and P = .023). The differences were most
      apparent at the highest contraction velocity (180 degrees /s). Dynamic muscle
      quality was associated with reduced walking endurance (R = 0.689, P = .006 and R
      = 0.550, P = .042 for initial and absolute claudication distance, respectively).
      The claudicating-limb group demonstrated a trend toward reduced static muscle
      quality compared with controls (22%, P = .084). The relative contribution of the
      soleus muscle to plantarflexion maximum voluntary contraction was significantly
      higher in the claudicating-limb and asymptomatic-limb groups than in controls (P
      = .012 and P = .018). CONCLUSIONS: The muscle strength of the plantarflexors in
      those with PAD-IC appears to be impaired at high contraction velocities. This may
      be explained by some reduction in gastrocnemii muscle quality and a greater
      reliance on the prominently type I-fibered soleus muscle. The reduced dynamic
      capability of the plantarflexor muscles was associated with disease severity and
      walking ability; therefore, efforts to improve plantarflexor power through
      dynamic exercise intervention are vital to maintain functional performance.

PMID- 25953023
TI  - Determination of the prevalence of trypanosome species in cattle from Monduli
      district, northern Tanzania, by loop mediated isothermal amplification.
AB  - Bovine African trypanosomosis (BAT) remains one of the major vector-borne
      diseases with serious impediment to cattle production and economic advancement in
      sub-Saharan Africa. The present study evaluated the performance of the
      trypanosome-species-specific loop-mediated isothermal amplification (LAMP), using
      parasite DNA obtained from 295 indigenous Tanzanian short horn Zebu (TSHZ) and
      Boran crosses in Monduli district within northern Tanzania, against routine
      microscopy on Giemsa-stained blood films. Compared to parasitological data in
      which the prevalence of BAT was estimated at 2.4% (95% CI 0.7-4.1%), LAMP
      increased the prevalence to 27.8% (95% CI 22.3-32.5%), of which 11.9% (95% CI 8.2
      15.6%) were monolytic infections with Trypanosoma vivax, while 13.6% (95% CI 9.7
      17.5%) were coinfections of either T. vivax and Trypanosoma brucei subspecies or
      T. vivax and Trypanosoma congolense, respectively. Among the T. brucei subspecies
      detected, 0.7% (95% CI 0-1.7%) were human-infective Trypanosoma brucei
      rhodesiense. Our study is in concordance with previous reports and suggests that
      LAMP is a potential tool for routine diagnosis of trypanosomes in domestic
      animals in BAT endemic regions. According to LAMP, T. vivax seems to be the
      predominant trypanosome species circulating among the indigenous Monduli cattle.
      Importantly, the detection of T. b. rhodesiense in cattle in such wildlife
      domestic-animal-human-interface areas poses a risk of contracting human African
      trypanosomiasis (HAT) by local communities and tourists. Continuous trypanosome
      surveillances in domestic animals, humans, and tsetse flies using sensitive and
      specific tests such as LAMP are recommended.

PMID- 25953024
TI  - The use of PCR technique in the identification of Mycobacterium species
      responsible for bovine tuberculosis in cattle and buffaloes in Pakistan.
AB  - Bovine tuberculosis is one of the important diseases of dairy and wild animals.
      The disease is prevalent all over the world, though developed countries have
      tremendously reduced the prevalence through eradication campaigns. The prevalence
      of disease in Pakistan on the basis of tuberculin testing or culture isolation of
      the organism has been reported previously. It is, however, important to use the
      latest diagnostic tools, i.e. PCR to confirm the type of Mycobacterium infecting
      the animals in Pakistan. Therefore, the present study was carried out to assess
      the utility of direct PCR on milk samples and nasal swabs to confirm the type of
      Mycobacterium infecting the animals. This study was carried out on 215 cattle and
      buffaloes of more than 2 years of age present at two livestock farms. The
      tuberculin results showed 22.5% prevalence at one farm and 25.9% at the other
      with an overall prevalence of 24.7%. The 92.5% of milk samples and/or nasal swabs
      showed positive PCR for Mycobacterium genus, 86.8% for Mycobacterium tuberculosis
      complex and 77.4% for Mycobacterium bovis. The M. bovis by PCR was detected in
      13.2% of milk samples, 24.5% of nasal swabs and 39.6% of both milk samples +
      nasal swabs. The results suggested that there are 60% higher chance for a nasal
      swab to yield a positive PCR for M. bovis than the milk sample. It can be
      concluded from the present study that tuberculin testing is a useful method in
      studying the prevalence of disease as the PCR for Mycobacterium genus was
      positive in 92.5%, M. tuberculosis complex in 86.8% and Mycobacterium bovis in
      77.4% cases.

PMID- 25953025
TI  - Indirect methods for predicting body composition of Boer crossbreds and
      indigenous goats from the Brazilian semiarid.
AB  - The aim of this study was to evaluate the correlation and to develop regression
      equations between the body composition obtained by the comparative slaughter and
      the neck composition and the ultrasound ribeye area (REAu) in goats from the
      Brazilian semiarid region. Forty-five intact male goats from three genetic groups
      were used: 15 Caninde, 15 Moxoto, and 15 F1 Boer x non-descript breed. Animals
      were randomly assigned to three feeding levels (ad libitum, 25 and 50%
      restriction) aimed to result in different slaughter weights and body composition,
      to fit the regression equations. The REAu was assessed between the 12th and 13th
      ribs with a 7.5 MHz linear transducer. The values of crude protein, ether
      extract, and water in the empty body showed high positive correlation (P < 0.01)
      with REAu and with the same values measured in the neck for all genetic groups.
      In addition, body composition was well predicted (R(2) > 0.80) from the REAu and
      from the neck composition.

PMID- 25953026
TI  - A practical guideline for intracranial volume estimation in patients with
      Alzheimer's disease.
AB  - BACKGROUND: Intracranial volume (ICV) is an important normalization measure used
      in morphometric analyses to correct for head size in studies of Alzheimer Disease
      (AD). Inaccurate ICV estimation could introduce bias in the outcome. The current
      study provides a decision aid in defining protocols for ICV estimation in
      patients with Alzheimer disease in terms of sampling frequencies that can be
      optimally used on the volumetric MRI data, and the type of software most suitable
      for use in estimating the ICV measure. METHODS: Two groups of 22 subjects are
      considered, including adult controls (AC) and patients with Alzheimer Disease
      (AD). Reference measurements were calculated for each subject by manually tracing
      intracranial cavity by the means of visual inspection. The reliability of
      reference measurements were assured through intra- and inter- variation analyses.
      Three publicly well-known software packages (Freesurfer, FSL, and SPM) were
      examined in their ability to automatically estimate ICV across the groups.
      RESULTS: Analysis of the results supported the significant effect of estimation
      method, gender, cognitive condition of the subject and the interaction among
      method and cognitive condition factors in the measured ICV. Results on sub
      sampling studies with a 95% confidence showed that in order to keep the accuracy
      of the interleaved slice sampling protocol above 99%, the sampling period cannot
      exceed 20 millimeters for AC and 15 millimeters for AD. Freesurfer showed
      promising estimates for both adult groups. However SPM showed more consistency in
      its ICV estimation over the different phases of the study. CONCLUSIONS: This
      study emphasized the importance in selecting the appropriate protocol, the choice
      of the sampling period in the manual estimation of ICV and selection of suitable
      software for the automated estimation of ICV. The current study serves as an
      initial framework for establishing an appropriate protocol in both manual and
      automatic ICV estimations with different subject populations.

PMID- 25953027
TI  - Evaluation of in vivo responses of sorafenib therapy in a preclinical mouse model
      of PTEN-deficient of prostate cancer.
AB  - BACKGROUND: Despite recent advances in the treatment for advanced prostate
      cancer, outcomes remain poor. This lack of efficacy has prompted the development
      of alternative treatment strategies. In the present study we investigate the
      effects of the multikinase inhibitor sorafenib in a genetically engineered mouse
      model of prostate cancer and explore the rational combination with the mTOR
      inhibitor everolimus. METHODS: Conditional prostate specific PTEN-deficient
      knockout mice were utilized to determine the pharmacodynamic and chemopreventive
      effects of sorafenib. This mouse model was also used to examine the therapeutic
      efficacy of sorafenib alone or in combination with everolimus. Preclinical
      efficacy was assessed by comparing the reduction of tumor burden, proliferation,
      angiogenesis and the induction of apoptosis. Molecular responses were assessed by
      immunohistochemical, TUNEL and western blot assays. RESULTS: Pharmacodynamic
      analysis revealed that a single dose of sorafenib decreased activation of the
      PI3K/AKT/mTOR signaling axis at doses of 30-60 mg/kg, but activated JAK/STAT3
      signaling. Levels of cleaved casapase-3 increased in a dose dependent manner.
      Chemoprevention studies showed that chronic sorafenib administration was capable
      of inhibiting tumor progression through the reduction of cancer cell
      proliferation, angiogenesis and the induction of apoptosis. In intervention
      models of established castration-naive and castration-resistant prostate cancer,
      treatment with sorafenib provided modest but statistically insignificant
      reduction in tumor burden. However, sorafenib significantly inhibited cancer cell
      proliferation and MVD but had minimal effects on the induction of apoptosis.
      Interestingly, the administration of sorafenib increased the expression levels of
      the androgen receptor, p-GSK3beta and p-ERK1/2 in castration-resistant prostate
      cancers. In both intervention models, combination therapy demonstrated a clear
      tendency of enhanced antitumor effects over monotherapy. Notably, the treatment
      combination of sorafenib and everolimus overcame therapeutic escape from single
      agent therapy in castration-resistant prostate cancers. CONCLUSIONS: In summary,
      we provide insights into the molecular responses of sorafenib therapy in a
      clinically relevant model of prostate cancer and present preclinical evidence for
      the development of targeted treatment strategies based on the use of multikinase
      inhibitors in combination with mTOR inhibitors for the treatment of advanced
      prostate cancer.

PMID- 25953028
TI  - Replay to the Editor regarding Prof Klek's letter -reference manuscript # YCLNU-D
      13-00298R2 Parenteral Nutrition Admixtures for Pediatric Patients Compounded with
      Highly Refined Fish Oil-Based Emulsion: Assessment of Physicochemical Stability.

PMID- 25953030
TI  - Coronary Artery Embolism Following Aortic Valve Replacement.

PMID- 25953031
TI  - NGSmirPlant: comprehensive characterization of the small RNA transcriptomes of
      plants.

PMID- 25953029
TI  - Modulating APOBEC expression enhances DNA vaccine immunogenicity.
AB  - DNA vaccines have failed to induce satisfactory immune responses in humans.
      Several mechanisms of double-stranded DNA (dsDNA) sensing have been described,
      and modulate DNA vaccine immunogenicity at many levels. We hypothesized that the
      immunogenicity of DNA vaccines in humans is suppressed by APOBEC (apolipoprotein
      B (APOB) mRNA-editing, catalytic polypeptide)-mediated plasmid degradation. We
      showed that plasmid sensing via STING (stimulator of interferon (IFN) genes) and
      TBK-1 (TANK-binding kinase 1) leads to IFN-beta induction, which results in
      APOBEC3A mRNA upregulation through a mechanism involving protein kinase C
      signaling. We also showed that murine APOBEC2 expression in HEK293T cells led to
      a 10-fold reduction in intracellular plasmid levels and plasmid-encoded mRNA, and
      a 2.6-fold reduction in GFP-expressing cells. A bicistronic DNA vaccine
      expressing an immunogen and an APOBEC2-specific shRNA efficiently silenced
      APOBEC2 both in vitro and in vivo, increasing the frequency of induced IFN-gamma
      secreting T cells. Our study brings new insights into the intracellular machinery
      involved in dsDNA sensing and how to modulate it to improve DNA vaccine
      immunogenicity in humans. 

PMID- 25953032
TI  - Driving continuity in cognitively impaired older drivers.
AB  - AIM: Cognitive impairment can negatively affect driving performance and increase
      the risk of driving errors, leading to vehicle crashes. We used a population
      based survey to identify the prevalence of cognitive impairments in older
      drivers. METHODS: A total of 10,073 older adults were enrolled in the National
      Center for Geriatrics and Gerontology - Study of Geriatric Syndromes. We
      characterized general cognitive impairment using the Mini-Mental State
      Examination (MMSE). We also used the National Center for Geriatrics and
      Gerontology-Functional Assessment Tool, which includes six tasks to assess word
      list memory, logical memory, attention and executive function, processing speed,
      and visuospatial skill. RESULTS: Just 15% of older women with moderate cognitive
      decline (MMSE <=20) drove, whereas 61% of older men with moderate cognitive
      decline drove. Cognitively normal participants (MMSE score 27 and over) scored
      significantly better on six cognitive tests compared with those with mild (MMSE
      score 21-26) or moderate cognitive decline, and those in the mild cognitive
      decline group scored significantly better on six cognitive tests than those in
      the moderate cognitive decline group. CONCLUSION: A total of 61% of older men
      with moderate cognitive decline did not cease driving. These older drivers showed
      poor cognitive performance in multiple domains compared with those with normal
      and mild cognitive decline. Further studies are required to clarify the
      relationships between cognitive decline and car crashes in these high-risk
      populations.

PMID- 25953033
TI  - Autonomy support for autonomous motivation in medical education.
AB  - BACKGROUND: Medical students often study only to fare well in their examinations
      or pursue a specific specialty, or study only those topics that they perceive to
      be useful in medical practice. The motivation for study in these cases comes from
      external or internal pressures or from the desire to obtain rewards. Self
      determination theory (SDT) classifies this type of motivation as controlled
      motivation and the type of motivation that comes from genuine interest or
      personal value as autonomous motivation. Autonomous motivation, in comparison
      with controlled motivation, has been associated with better learning, academic
      success, and less exhaustion. SDT endorses autonomous motivation and suggests
      that autonomy support is important for autonomous motivation. The meaning of
      autonomy is misinterpreted by many. This article tries to focus on how to be
      autonomy-supportive in medical education. DISCUSSION: Autonomy support refers to
      the perception of choice in learning. Some of the ways of supporting autonomy in
      medical education are small group teaching, problem-based learning, and gradual
      increase in responsibility of patients. Autonomy-supportive teaching behavior is
      not a trait and can be learned. Autonomy support in medical education is not
      limited to bringing in changes in the medical curriculum for students; it is
      about an overall change in the way of thinking and working in medical schools
      that foster autonomy among those involved in education. Research into autonomy in
      medical education is limited. Some topics that need to be investigated are the
      ideas and perceptions of students and teachers about autonomy in learning.
      CONCLUSION: Autonomy support in medical education can enhance autonomous
      motivation of students for medical study and practice and make them autonomy
      supportive in their future medical practice and teaching.

PMID- 25953034
TI  - [Not Available].

PMID- 25953035
TI  - [An update on ejaculation physiology and premature ejaculation definition,
      prevalence data, and etiology].
AB  - Ejaculation consists of two synchronized phases: a) emission, the contraction of
      the vas deferens, prostate and seminal vesicles and bladder neck expelling the
      seminal fluid to the urethra; it is mediated by sympathetic nerves, and b)
      expulsion, seminal fluid outward propulsion by the rhythmic contraction of
      perineal muscles. Ejaculation results from a complex spinal reflex having its
      essential components within the lumbosacral cord. The main afferent signals
      derive from mechanical stimulation of the glans penis and are conveyed by sacral
      sensory roots. The ejaculatory reflex is under strong modulatory influence from
      the brain through both facilitatory and inhibitory descending signals. Several
      central neurotransmitters including serotonin and dopamine modulate the
      ejaculatory reflex. The intravaginal ejaculatory latency time (IELT), measured or
      estimated, provides clinically useful assessment of the ejaculatory reflex. The
      new DSM-5 definition of premature ejaculation (PE) includes a specified time to
      ejaculation criterion (IELT of about one minute or shorter). Four subtypes of PE,
      showing different prevalence rates, have been proposed. PE etiology is
      multifactorial with interacting psychological and biological factors contributing
      to the disorder. A number of genetic polymorphisms related to serotonin and
      dopamine neurotransmission may predispose the bearers to developing PE. High
      prevalence rates of PE have been found in patients with chronic prostatitis,
      hyperthyroidism, and premature ejaculation. 

PMID- 25953036
TI  - [Detection and diagnosis of the premature ejaculation in the clinical practice].
AB  - Recently, a new classification of the premature ejaculation has been proposed.
      According to this classification, four clinical forms are distinguished: primary
      premature ejaculation, secondary or acquired premature ejaculation, normal
      variant that appears in certain situations and a false premature ejaculation that
      is given in misinformed patients or with exaggerate sexual expectations. To know
      these clinical forms is important for the clinical boarding of this sexual
      disorder. In the same way, the detection of premature ejaculation in medical
      practise requires doctors being receptive and suitable to make an active
      detection into risk groups for this sexual dysfunction, also describe in the
      present work. Furthermore, essential aspects of the clinical interview in
      patients with premature ejaculation, criteria to get an accurate diagnosis, and
      basic aspects of the physical exploration, complementary studies and main
      specific questionnaires are described. 

PMID- 25953037
TI  - [Pharmacological treatment of the premature ejaculation].
AB  - Biomedical approach to premature ejaculation (PE) has permited a better
      phisiopatologycal knowledge and so the use of pharmacological agents for the
      treatment of this sexual dysfuncion. Most of the studies to evaluate the eficacy
      of these drugs were not carried at all the parameters which actually define PE:
      intravaginal ejaculatory latencie time (IELT) tested with watch, ejaculation
      control self perception cuantification (questionaries) and cuantification of
      generated consequences in patient and partner, if it existes. For this reason, it
      is difficult to analyse the scientific evidence and we use medicines with no
      approved indication for PE ("off label"). This text is a review of
      pharmacologycal agents with no approved indication (PDE type 5 inhibitors, alpha
      blockers, tramadol, SSRI, clomipramine), and pharmacologycal agents developed to
      be used in the treatment of PE and having got indication in this sexual
      dysfunction or "on label" drugs (topic anesthesics, dapoxetine). 

PMID- 25953038
TI  - [Sexological intervention on premature ejaculation].
AB  - Strategies, recommendations and techniques proposed by sex therapy for
      intervention on premature ejaculation, have represented for nearly four decades
      the most effective model of intervention in this sexual dysfunction, which
      currently is complemented by the efficacy of dapoxetine drug treatment. Clinical
      experience and recent studies support that combined intervention offers the best
      therapeutic results. In addition in sex therapy, etiologic diagnosis is obtained
      from the analysis of the interrelationship of the couple. Diagnostic and
      therapeutic intervention has to be always centered in the relationship, so the
      techniques and resources must be applied with the expectation of being
      implemented in the sexual interaction. It will therefore be the relationship that
      receive treatment, even if medication is used for one of the members of the
      couple. On the other hand, this model of intervention can be implemented by a
      professional with training, although not necessarily a specialist. 

PMID- 25953039
TI  - The principles, procedures and pitfalls in identifying archaeological and
      historical wood samples.
AB  - BACKGROUND: The science of wood anatomy has evolved in recent decades to add
      archaeological and historical wood to its repertoire of documenting and
      characterizing modern and fossil woods. The increasing use of online wood anatomy
      databases and atlases has fostered the adoption of an international consensus
      regarding terminology, largely through the work of the International Association
      of Wood Anatomists (IAWA). SCOPE AND CONCLUSIONS: This review presents an
      overview for the general reader of the current state of principles and procedures
      involved in the study of the wood anatomy of archaeological and historical
      specimens, some of which may be preserved through charring, waterlogging,
      desiccation or mineral replacement. By means of selected case studies, the review
      evaluates to what extent varying preservation of wood anatomical characteristics
      limits the level of identification to taxon. It assesses the role played by
      increasingly accessible scanning electron microscopes and complex optical
      microscopes, and whether these, on the one hand, provide exceptional
      opportunities for high-quality imaging and analysis of difficult samples, but, on
      the other hand, might be misleading the novice into thinking that advanced
      technology can be a substitute for specialized botanical training in wood
      anatomy.

PMID- 25953040
TI  - Transitions between self-compatibility and self-incompatibility and the evolution
      of reproductive isolation in the large and diverse tropical genus Dendrobium
      (Orchidaceae).
AB  - BACKGROUND AND AIMS: The evolution of interspecific reproductive barriers is
      crucial to understanding species evolution. This study examines the contribution
      of transitions between self-compatibility (SC) and self-incompatibility (SI) and
      genetic divergence in the evolution of reproductive barriers in Dendrobium, one
      of the largest orchid genera. Specifically, it investigates the evolution of pre-
      and postzygotic isolation and the effects of transitions between compatibility
      states on interspecific reproductive isolation within the genus. METHODS: The
      role of SC and SI changes in reproductive compatibility among species was
      examined using fruit set and seed viability data available in the literature from
      86 species and ~2500 hand pollinations. The evolution of SC and SI in Dendrobium
      species was investigated within a phylogenetic framework using internal
      transcribed spacer sequences available in GenBank. KEY RESULTS: Based on data
      from crossing experiments, estimations of genetic distance and the results of a
      literature survey, it was found that changes in SC and SI significantly
      influenced the compatibility between species in interspecific crosses. The number
      of fruits produced was significantly higher in crosses in which self-incompatible
      species acted as pollen donor for self-compatible species, following the SI * SC
      rule. Maximum likelihood and Bayesian tests did not reject transitions from SI to
      SC and from SC to SI across the Dendrobium phylogeny. In addition, postzygotic
      isolation (embryo mortality) was found to evolve gradually with genetic
      divergence, in agreement with previous results observed for other plant species,
      including orchids. CONCLUSIONS: Transitions between SC and SI and the gradual
      accumulation of genetic incompatibilities affecting postzygotic isolation are
      important mechanisms preventing gene flow among Dendrobium species, and may
      constitute important evolutionary processes contributing to the high levels of
      species diversity in this tropical orchid group.

PMID- 25953042
TI  - Microfluidic Generation of Porous Particles Encapsulating Spongy Graphene for Oil
      Absorption.
AB  - Porous particles encapsulating spongy graphene are generated from a microfluidic
      device and used as adsorbents for water treatment. The amphiphilic surface
      characteristics result from hydrophobic graphene cores and hydrophilic shells
      and, together with the porous structure, ensure that the particles have the
      ability to absorb oils that are either floating on the water or under water. 

PMID- 25953041
TI  - Carotenoid accumulation during tomato fruit ripening is modulated by the auxin
      ethylene balance.
AB  - BACKGROUND: Tomato fruit ripening is controlled by ethylene and is characterized
      by a shift in color from green to red, a strong accumulation of lycopene, and a
      decrease in beta-xanthophylls and chlorophylls. The role of other hormones, such
      as auxin, has been less studied. Auxin is retarding the fruit ripening. In
      tomato, there is no study of the carotenoid content and related transcript after
      treatment with auxin. RESULTS: We followed the effects of application of various
      hormone-like substances to "Mature-Green" fruits. Application of an ethylene
      precursor (ACC) or of an auxin antagonist (PCIB) to tomato fruits accelerated the
      color shift, the accumulation of lycopene, alpha-, beta-, and delta-carotenes and
      the disappearance of beta-xanthophylls and chlorophyll b. By contrast,
      application of auxin (IAA) delayed the color shift, the lycopene accumulation and
      the decrease of chlorophyll a. Combined application of IAA + ACC led to an
      intermediate phenotype. The levels of transcripts coding for carotenoid
      biosynthesis enzymes, for the ripening regulator Rin, for chlorophyllase, and the
      levels of ethylene and abscisic acid (ABA) were monitored in the treated fruits.
      Correlation network analyses suggest that ABA, may also be a key regulator of
      several responses to auxin and ethylene treatments. CONCLUSIONS: The results
      suggest that IAA retards tomato ripening by affecting a set of (i) key
      regulators, such as Rin, ethylene and ABA, and (ii) key effectors, such as genes
      for lycopene and beta-xanthophyll biosynthesis and for chlorophyll degradation.

PMID- 25953043
TI  - Comorbid mental illness and criminalness implications for housing and treatment.
AB  - The relationship between mental illness, violence, and criminal behavior is
      complex, and involves a multifaceted interaction of biological, psychological,
      and social processes. In this article, we review the emerging research that
      examines the neurobiological and psychological factors that distinguish between
      persons with mental illness who do and who do not engage in crime and violence.
      Additionally, a novel model for understanding the interaction between mental
      illness and criminalness is proposed. (As defined by Morgan and colleagues,
      criminalness is defined as behavior that breaks laws and social conventions
      and/or violates the rights and wellbeing of others.) Stemming from this model and
      outlined research, we argue that management and treatment approaches should
      target the co-occurring domains of mental illness and criminalness to improve
      criminal and psychiatric outcomes. Specifically, we discuss and propose effective
      housing (management) and biopsychosocial intervention strategies for improving
      outcomes. 

PMID- 25953044
TI  - Chloride transport activities of trans- and cis-amide-linked bisureas.
AB  - Of the bisurea compounds linked through trans- and cis-benzanilide spacers, the
      cis-amide derivatives were found to be effective in chloride transport, using
      which a stimuli-responsive mobile carrier was devised. 

PMID- 25953045
TI  - Reply.

PMID- 25953046
TI  - Cyclopeptide RA-V inhibits cell adhesion and invasion in both estrogen receptor
      positive and negative breast cancer cells via PI3K/AKT and NF-kappaB signaling
      pathways.
AB  - Cyclopeptide RA-V has potent anti-tumor and anti-angiogenic activities, but its
      potential anti-metastatic activity is unknown. Cancer cells acquire invasive
      ability to degrade and adhere to extracellular matrix (ECM), allowing them to
      migrate to adjacent tissues and ultimately metastasize. Hence, the present study
      aimed to investigate the effects of RA-V on cell adhesion, migration, invasion
      and matrix degradation, and its underlying mechanism in two human breast cancer
      cell lines MCF-7 (ER-positive) and MDA-MB-231 (ER-negative). Our results
      demonstrated that RA-V (12.5 nM) can significantly inhibit breast cancer cell
      adhesion and migration via interfering cofilin signaling and chemokine receptors
      involved in cell migration. RA-V reduced the expressions of vascular
      intracellular adhesion molecule (VCAM), intracellular adhesion molecule (ICAM),
      focal adhesion kinase (FAK) and integrins. The activities and expressions of
      matrix metalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases
      (TIMPs) and urokinase-type of plasminogen activator (uPA) were also inhibited by
      RA-V. Furthermore, RA-V inhibits the expressions of EGFR, PI3K/AKT and NF-kappaB
      signaling molecules, and reduces the binding of beta-estradiol to ER via
      affecting binding ability of ER in MCF-7 cells. RA-V inhibits breast cancer cell
      migration, adhesion and ECM degradation in vitro, implying that RA-V is a
      potential anti-metastatic agent in breast cancer, and likely acts via PI3K/AKT
      and NF-kappaB signaling pathways in both ER-positive and ER-negative breast
      cancer cells.

PMID- 25953047
TI  - Collective memory: a new arena of cognitive study.
AB  - Collective memory refers to recollection of events shared by a group. The topic
      has been of central interest in the humanities, but recently researchers have
      begun empirical studies. Topics such as how people remember a war or how quickly
      Americans forget their presidents can be studied objectively. 

PMID- 25953052
TI  - Caffeine-induced mania in a patient with caffeine use disorder: A case report.
AB  - BACKGROUND, OBJECTIVES AND METHODS: Here, we report a case of a patient who
      reported using high dose caffeine and was observed with multiple episodes of
      caffeine-induced mania with psychotic features and met criteria for caffeine use
      disorder. RESULTS: To our knowledge, this is the first reported case of caffeine
      induced mania in a patient that also specifically met criteria for caffeine use
      disorder. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: This case supports evidence
      that caffeine use disorder should be considered for inclusion in future
      diagnostic manuals as a potential drug of abuse pending additional research.

PMID- 25953056
TI  - An exploratory analysis linking neuropsychological testing to quantification of
      tractography using High Definition Fiber Tracking (HDFT) in military TBI.
AB  - To realize the potential value of tractography in traumatic brain injury (TBI),
      we must identify metrics that provide meaningful information about functional
      outcomes. The current study explores quantitative metrics describing the spatial
      properties of tractography from advanced diffusion imaging (High Definition Fiber
      Tracking, HDFT). In a small number of right-handed males from military TBI (N =
      7) and civilian control (N = 6) samples, both tract homologue symmetry and tract
      spread (proportion of brain mask voxels contacted) differed for several tracts
      among civilian controls and extreme groups in the TBI sample (high scorers and
      low scorers) for verbal recall, serial reaction time, processing speed index, and
      trail-making. Notably, proportion of voxels contacted in the arcuate fasciculus
      distinguished high and low performers on the CVLT-II and PSI, potentially
      reflecting linguistic task demands, and GFA in the left corticospinal tract
      distinguished high and low performers in PSI and Trail Making Test Part A,
      potentially reflecting right hand motor response demands. The results suggest
      that, for advanced diffusion imaging, spatial properties of tractography may add
      analytic value to measures of tract anisotropy. 

PMID- 25953058
TI  - Transplant surgeon who fast tracked patients is found not guilty of attempted
      manslaughter.

PMID- 25953060
TI  - Making Markets in Long-Term Care: Or How a Market Can Work by Being Invisible.
AB  - Many Western countries have introduced market principles in healthcare. The newly
      introduced financial instrument of "care-intensity packages" in the Dutch long
      term care sector fit this development since they have some characteristics of a
      market device. However, policy makers and care providers positioned these
      instruments as explicitly not belonging to the general trend of marketisation in
      healthcare. Using a qualitative case study approach, we study the work that the
      two providers have done to fit these instruments to their organisations and how
      that enables and legitimatises market development. Both providers have done
      various types of work that could be classified as market development, including
      creating accounting systems suitable for markets, redefining public values in the
      context of markets, and starting commercial initiatives. Paradoxically, denying
      the existence of markets for long-term care and thus avoiding ideological debates
      on the marketisation of healthcare has made the use of market devices all the
      more likely. Making the market invisible seems to be an operative element in
      making the market work. Our findings suggest that Dutch long-term care reform
      points to the need to study the 'making' rather than the 'liberalising' of
      markets and that the study of healthcare markets should not be confined to those
      practices that explicitly label themselves as such.

PMID- 25953059
TI  - Response rates for patient-reported outcomes using web-based versus paper
      questionnaires: comparison of two invitational methods in older colorectal cancer
      patients.
AB  - BACKGROUND: Improving questionnaire response rates is an everlasting issue for
      research. Today, the Internet can easily be used to collect data quickly.
      However, collecting data on the Internet can lead to biased samples because not
      everyone is able to access or use the Internet. The older population, for
      example, is much less likely to use the Internet. The Patient-Reported Outcomes
      Following Initial Treatment and Long-Term Evaluation of Survivorship (PROFILES)
      registry offers a platform to collect Web-based and paper questionnaires and to
      try different measures to improve response rates. OBJECTIVE: In this study, our
      aim was to study the influence of two methods of invitation on the response rate.
      Our second aim was to examine the preference of questionnaire mode of
      administration (paper or Web-based) for the older patient in particular. METHODS:
      To test these two invitational methods, 3406 colorectal cancer patients between
      ages 18 and 85 years received an invitation containing an access code for the Web
      based questionnaire. They could also request a paper questionnaire with an
      included reply card (paper-optional group). In contrast, 179 randomly selected
      colorectal cancer patients received a paper questionnaire with the invitation
      (paper-included group). They could also choose to fill out the Web-based
      questionnaire with the included access code. RESULTS: Response rates did not
      differ between the paper-optional and the paper-included groups (73.14%,
      2491/3406 and 74.9%, 134/179, P=.57). In the paper-optional group, online
      response was significantly higher when compared to the paper-included group
      (41.23%, 1027/2491 vs 12.7%, 17/134, P<.001). The majority of online respondents
      responded after the first invitation (95.33%, 979/1027), which was significantly
      higher than the paper respondents (52.19%, 764/1464, P<.001). Respondents aged 70
      years and older chose to fill out a paper questionnaire more often (71.0%,
      677/954). In the oldest age group (>=80 years), 18.2% (61/336) of the respondents
      filled out a Web-based questionnaire. CONCLUSIONS: The lack of difference in
      response rates between invitation modes implies that researchers can leave out a
      paper questionnaire at invitation without lowering response rates. It may be
      preferable not to include a paper questionnaire because more respondents then
      will fill out a Web-based questionnaire, which will lead to faster available
      data. However, due to respondent preference, it is not likely that paper
      questionnaires can be left out completely in the near future.

PMID- 25953057
TI  - Dyslexia and language impairment associated genetic markers influence cortical
      thickness and white matter in typically developing children.
AB  - Dyslexia and language impairment (LI) are complex traits with substantial genetic
      components. We recently completed an association scan of the DYX2 locus, where we
      observed associations of markers in DCDC2, KIAA0319, ACOT13, and FAM65B with
      reading-, language-, and IQ-related traits. Additionally, the effects of reading
      associated DYX3 markers were recently characterized using structural neuroimaging
      techniques. Here, we assessed the neuroimaging implications of associated DYX2
      and DYX3 markers, using cortical volume, cortical thickness, and fractional
      anisotropy. To accomplish this, we examined eight DYX2 and three DYX3 markers in
      332 subjects in the Pediatrics Imaging Neurocognition Genetics study. Imaging
      genetic associations were examined by multiple linear regression, testing for
      influence of genotype on neuroimaging. Markers in DYX2 genes KIAA0319 and FAM65B
      were associated with cortical thickness in the left orbitofrontal region and
      global fractional anisotropy, respectively. KIAA0319 and ACOT13 were suggestively
      associated with overall fractional anisotropy and left pars opercularis cortical
      thickness, respectively. DYX3 markers showed suggestive associations with
      cortical thickness and volume measures in temporal regions. Notably, we did not
      replicate association of DYX3 markers with hippocampal measures. In summary, we
      performed a neuroimaging follow-up of reading-, language-, and IQ-associated DYX2
      and DYX3 markers. DYX2 associations with cortical thickness may reflect
      variations in their role in neuronal migration. Furthermore, our findings
      complement gene expression and imaging studies implicating DYX3 markers in
      temporal regions. These studies offer insight into where and how DYX2 and DYX3
      risk variants may influence neuroimaging traits. Future studies should further
      connect the pathways to risk variants associated with neuroimaging/neurocognitive
      outcomes. 

PMID- 25953061
TI  - Functional adaptation of the human beta-cells after frequent exposure to
      noradrenaline.
AB  - Physical training decreases glucose- and arginine-stimulated insulin secretion.
      The mechanism by which the pancreatic beta-cells adapt to the training status of
      the individual is not known. We hypothesized that the adaptation is mediated via
      the frequent exercise-induced increases in sympathetic activity. Simulation of
      exercise-induced increases in plasma noradrenaline (NA) concentrations was
      carried out in nine untrained men (age: 25 +/- 1 years (mean +/- SEM); BMI: 24 +/
      1 kg m(-2) ), who received infusions of NA (0.2 MUg kg(-1) min(-1) ) for 45 min
      every day for 10 days. The insulin response to glucose was measured during
      hyperglycaemic (20 mmol l(-1) ) clamps before and after the NA infusion period.
      During NA infusions mean arterial blood pressure increased (from 89 +/- 2 to 110
      +/- 5 mmHg, P < 0.05) and heart rate decreased (from 78 +/- 7 to 69 +/- 12 beats
      min(-1) , P < 0.05). During NA infusions plasma insulin concentrations decreased
      to nadir by 68% (P < 0.05). Fasting plasma glucose and insulin were not different
      at the two clamps (5.3 +/- 0.1 and 5.3 +/- 0.3 mmol l(-1) ; 47 +/- 15 and 31 +/-
      4 pmol l(-1) , respectively). Plasma glucose concentrations during the
      hyperglycaemic clamps were similar (P > 0.05) and averaged 19.9 +/- 0.1 mmol l(
      1) with a coefficient of variation of 3.8 +/- 0.3%, while the insulin response
      decreased (P < 0.05) by 26 +/- 2% after the 10 days of NA infusions. It is
      concluded that NA mediates the adaptation of the beta-cells seen in trained
      people.

PMID- 25953062
TI  - Characteristic points and cycles in planar kinematics with application to the
      human gait.
AB  - PURPOSE: We present a novel method to process kinematical data typically coming
      from measurements of joints. This method will be illustrated through two
      examples. METHODS: We adopt theoretical kinematics together with the principle of
      least action. We use motion and inverse motion for describing the whole
      experimental situation theoretically. RESULTS: By using the principle of least
      action, the data contain information about inherent reference points, which we
      call characteristic points. These points are unique for direct and inverse
      motion. They may be viewed as centers of the fixed and moving reference systems.
      The respective actions of these characteristic points are analytically
      calculated. The sum of these actions defines the kinematical action. This sum is
      by design independent of the choice of reference system. The minimality of the
      kinematical action can be used again to select numerically one representative
      cycle in empirically given, approximately periodic motions. Finally, we
      illustrate the theoretical approach making use of two examples worked out, hinge
      movement and the sagittal component of the movement of a human leg during gait.
      CONCLUSIONS: This approach enables automatic cycle choices for evaluating large
      databases in order to compare and to distinguish empirically given movements. The
      procedure can be extended to three dimensional movements.

PMID- 25953063
TI  - Oral health in children and adolescents with haemophilia.
AB  - INTRODUCTION: Bleeding disorders are certainly one of the most difficult health
      conditions among health professionals. The haemophilia requires special care in
      dentistry mainly due to highly vascularized oral cavity. AIM: The objective of
      this study was to determine oral health conditions of children and adolescents
      with haemophilia at a haematology centre. METHODS: The sample was composed of 40
      children and adolescents aged 1-18 years. Data collection occurred by means of a
      questionnaire about social and economical conditions, and an examination of the
      oral cavity. The decayed, missing and filled deciduous teeth (dmft), decayed,
      missing and filled permanent teeth (DMFT) and gingival bleeding (allows the
      determination of gingival bleeding) epidemiological indexes were evaluated.
      RESULTS: When evaluating caries experience, the mean value for the dmft index was
      3.4 for the deciduous dentition, DMFT score of 0.9 for mixed-dentition, and 2.9
      for permanent dentition. The mean value for the gingival bleeding index was
      similar in all three phases of development, showing a mean value of 1.74.
      CONCLUSION: The majority of the children and adolescents demonstrated
      unsatisfactory oral health.

PMID- 25953064
TI  - Statistics of non-affine defect precursors: tailoring defect densities in
      colloidal crystals using external fields.
AB  - Coarse-graining atomic displacements in a solid produces both local affine
      strains and "non-affine" fluctuations. Here we study the equilibrium dynamics of
      these coarse grained quantities to obtain space-time dependent correlation
      functions. We show how a subset of these thermally excited, non-affine
      fluctuations act as precursors for the nucleation of lattice defects and suggest
      how defect probabilities may be altered by an experimentally realisable
      "external" field conjugate to the global non-affinity parameter. Our results are
      amenable to verification in experiments on colloidal crystals using commonly
      available holographic laser tweezer and video microscopy techniques, and may lead
      to simple ways of controlling the defect density of a colloidal solid. 

PMID- 25953066
TI  - Heterometallic Coordination Polymers Assembled from Trigonal Trinuclear Fe2Ni
      Pivalate Blocks and Polypyridine Spacers: Topological Diversity, Sorption, and
      Catalytic Properties.
AB  - Linkage of the trigonal complex [Fe2NiO(Piv)6] (where Piv(-) = pivalate) by a
      series of polypyridine ligands, namely, tris(4-pyridyl)triazine (L(2)), 2,6-bis(3
      pyridyl)-4-(4-pyridyl)pyridine (L(3)), N-(bis-2,2-(4-pyridyloxymethyl)-3-(4
      pyridyloxy)propyl))pyridone-4 (L(4)), and 4-(N,N-diethylamino)phenyl-bis-2,6-(4
      pyridyl)pyridine (L(5)) resulted in the formation of novel coordination polymers
      [Fe2NiO(Piv)6(L(2))]n (2), [Fe2NiO(Piv)6(L(3))]n (3), [Fe2NiO(Piv)6(L(4))]n.nHPiv
      (4), and [{Fe2NiO(Piv)6}4{L(5)}6]n.3nDEF (5, where DEF is N,N-diethylformamide),
      which were crystallographically characterized. The topological analysis of 3, 4,
      and 5 disclosed the 3,3,4,4-connected 2D (3, 4) or 3,4,4-connected 1D (5)
      underlying networks which, upon further simplification, gave rise to the uninodal
      3-connected nets with the respective fes (3, 4) or SP 1-periodic net (4,4)(0,2)
      (5) topologies, driven by the cluster [Fe2Ni(MU3-O)(MU-Piv)6] nodes and the
      polypyridine MU3-L(3,4) or MU2-L(5) blocks. The obtained topologies were compared
      with those identified in other closely related derivatives [Fe2NiO(Piv)6(L(1))]n
      (1) and {Fe2NiO(Piv)6}8{L(6)}12 (6), where L(1) and L(6) are tris(4
      pyridyl)pyridine and 4-(N,N-dimethylamino)phenyl-bis-2,6-(4-pyridyl)pyridine,
      respectively. It was shown that a key structure-driven role in defining the
      dimensionality and topology of the resulting coordination network is played by
      the type of polypyridine spacer. Compounds 2 and 3 possess a porous structure, as
      confirmed by the N2 and H2 sorption data at 78 K. Methanol and ethanol sorption
      by 2 was also studied indicating that the pores filled by these substrates did
      not induce any structural rearrangement of this sorbent. Additionally, porous
      coordination polymer 2 was also applied as a heterogeneous catalyst for the
      condensation of salicylaldehyde or 9-anthracenecarbaldehyde with malononitrile.
      The best activity of 2 was observed in the case of salicylaldehyde substrate,
      resulting in up to 88% conversion into 2-imino-2H-chromen-3-carbonitrile. 

PMID- 25953065
TI  - Uveitis in spondyloarthritis including psoriatic arthritis, ankylosing
      spondylitis, and inflammatory bowel disease.
AB  - Uveitis is a common complication of spondyloarthritis. The "phenotype" of the
      uveitis characteristic of ankylosing spondylitis (sudden onset, anterior,
      unilateral, recurrent, more often male) may differ from the phenotype often seen
      with either psoriatic arthritis or inflammatory bowel disease (insidious onset,
      anterior and intermediate, bilateral, chronic, and/or more often female). The
      frequency of uveitis is also much greater in association with ankylosing
      spondylitis than with either inflammatory bowel disease or psoriasis. Uveitis may
      affect the choice of therapy and can rarely be a complication of therapy. Uveitis
      and arthritis also co-exist in several animal models. 

PMID- 25953068
TI  - Treatment-related differences in health related quality of life and disease
      specific symptoms among colon cancer survivors: results from the population-based
      PROFILES registry.
AB  - BACKGROUND: The goal of this study was to compare health related quality of life
      (HRQoL) and disease-specific symptoms between colon cancer patients treated with
      surgery only (SU) and surgery and adjuvant chemotherapy (SU+adjCT). Results were
      stratified for those aged <70 and ?70years. HRQoL of patients was also compared
      with an age- and sex-matched normative population. METHODS: Patients diagnosed
      with colon cancer between January 2000 and June 2009, as registered within the
      population-based Eindhoven Cancer Registry, received a questionnaire on HRQoL
      (European Organization for Research and Treatment of Cancer (EORTC) Quality of
      Life Questionnaire version 3.0 (QLQ-C30)) and disease-specific symptoms (EORTC
      QLQ-Colorectal 38 (EORTC QLQ-CR38)) in 2010. The first was also completed by the
      normative population (n=685). RESULTS: 1606 (72%) colon cancer survivors
      responded to our questionnaire. 1542 colon cancer patients treated with SU
      (n=1031) or SU+adjCT (n=493) were included in this study. In colon cancer
      patients aged <70years and aged ?70 no statistical significant differences on the
      subscales of the EORTC QLQ-C30 or the EORTC QLQ-CR38 were observed between
      patients treated with SU and SU+adjCT. Colon cancer patients aged <70years either
      treated with SU or SU+adjCT reported significantly more insomnia, diarrhoea and
      financial problems compared with the normative population. No differences in
      HRQoL were found between colon cancer patients aged ?70years either treated with
      SU or SU+adjCT and the normative population. CONCLUSION: No differences in HRQoL
      and disease-specific symptoms were found between patients treated with SU versus
      SU+adjCT in both younger and elderly colon cancer patients. Withholding patients
      adjCT, based on concerns for long-term HRQoL or disease-specific symptoms does
      therefore not seem plausible.

PMID- 25953069
TI  - Magnetoelectric 'spin' on stimulating the brain.
AB  - AIM: The in vivo study on imprinting control region mice aims to show that
      magnetoelectric nanoparticles may directly couple the intrinsic neural activity
      induced electric fields with external magnetic fields. METHODS: Approximately 10
      ug of CoFe2O4-BaTiO3 30-nm nanoparticles have been intravenously administrated
      through a tail vein and forced to cross the blood-brain barrier via a d.c. field
      gradient of 3000 Oe/cm. A surgically attached two-channel electroencephalography
      headmount has directly measured the modulation of intrinsic electric waveforms by
      an external a.c. 100-Oe magnetic field in a frequency range of 0-20 Hz. RESULTS:
      The modulated signal has reached the strength comparable to that due the regular
      neural activity. CONCLUSION: The study opens a pathway to use multifunctional
      nanoparticles to control intrinsic fields deep in the brain.

PMID- 25953070
TI  - Mobility device use in older adults and incidence of falls and worry about
      falling: findings from the 2011-2012 national health and aging trends study.
AB  - OBJECTIVES: To examine the prevalence of mobility device use in community
      dwelling older adults in the United States and to investigate the incidence of
      falls and worry about falling according to type and number of mobility devices
      used. DESIGN: Analysis of cross-sectional and longitudinal data from the 2011-12
      National Health and Aging Trends Study. SETTING: In-person interviews in the
      homes of study participants. PARTICIPANTS: Nationally representative sample of
      Medicare beneficiaries (n=7,609). MEASUREMENTS: Participants were asked about
      mobility device use (e.g., canes, walkers, wheelchairs and scooters) in the last
      month, 1-year fall history and worry about falling. RESULTS: Twenty-four percent
      of adults aged 65 and older reported mobility device use in 2011, and 9.3%
      reported using multiple devices within the last month. Mobility device use
      increased with advancing age and was associated with nonwhite race and ethnicity,
      female sex, lower education level, greater multimorbidity, and obesity (all
      P<.001). Adjusting for demographic and health characteristics and physical
      function, the incidence of falls and recurrent falls was not associated with the
      use of multiple devices or any particular type of mobility device. Activity
      limiting worry about falling was significantly higher in cane-only users than in
      nonusers. CONCLUSION: The percentage of older adults reporting mobility device
      use is higher than results from previous national surveys, and multiple device
      use is common in those who use any device. Mobility device use is not associated
      with greater incidence of falls. Cane-only users may compensate for worry about
      falling by limiting activity.

PMID- 25953071
TI  - Effect of modification degree of nanohydroxyapatite on biocompatibility and
      mechanical property of injectable poly(methyl methacrylate)-based bone cement.
AB  - The objective of this study is to prepare a biocompatible
      nanohydroxyapatite/poly(methyl methacrylate) (HA/PMMA) composite bone cement,
      which has good mechanical property and can be used for vertebroplasty. Up to 40
      wt % of nanohydroxyapatite (nano-HA) in the power, which was surface modified
      with poly(methylmethacrylate-co-gamma-methacryloxypropyl timethoxysilane) [P(MMA
      co-MPS)] copolymer, was incorporated into the composite bone cement. The content
      of P(MMA-co-MPS) on the surface of nano-HA (18.7%, 22.8%, and 26%) was determined
      through thermogravimetric analysis (TGA). The morphology of biomineralized
      surface of composite bone cement was observed under scanning electron microscope
      (SEM). The mechanical measurements of the composite cements implied that the
      interfacial interaction between the HA and PMMA matrix may be greatly enhanced
      after surface modification of HA. Biochemical assays indicated that the HA/PMMA
      bone cement had no cytotoxicity and induced no hemolysis. The cell adhesion and
      alkaline phosphatase (ALP) activity assays indicated that the biocompatibility of
      HA/PMMA bone cement could be promoted, demonstrating that it can be used as an
      ideal weight-bearing bone repair materials on clinical application.

PMID- 25953072
TI  - Modeling the contraction of the pelvic floor muscles.
AB  - We performed numerical simulation of voluntary contraction of the pelvic floor
      muscles to evaluate the resulting displacements of the organs and muscles.
      Structures were segmented in Magnetic Resonance (MR) images. Different material
      properties and constitutive models were attributed. The Finite Element Method was
      applied, and displacements were compared with dynamic MRI findings. Numerical
      simulation showed muscle magnitude displacement ranging from 0 to 7.9 mm, more
      evident in the posterior area. Accordingly, the anorectum moved more than the
      uterus and bladder. Dynamic MRI showed less 0.2 mm and 4.1 mm muscle dislocation
      in the anterior and cranial directions, respectively. Applications of this model
      include evaluating muscle impairment, subject-specific mesh implant planning, or
      effectiveness of rehabilitation. 

PMID- 25953074
TI  - Influence of deep-frying using various commercial oils on acrylamide formation in
      French fries.
AB  - This study investigated the effect of different types of commercial oils (rice
      bran oil, shortening oil, high-oleic rapeseed oil, low-erucic acid rapeseed oil,
      blend oil A and blend oil B) and frying cycles on acrylamide formation during the
      preparation of French fries by deep-frying. Frying was carried out in
      intermittent mode (two batches each for 12 min without any time lag) and repeated
      for 600 frying cycles. Results indicated that the French fries that were fried in
      oils having lower heat transfer coefficients contained lower acrylamide
      concentrations (913 ug kg(-1)), whereas those fried with oils having higher heat
      transfer coefficients contained higher acrylamide concentrations (1219 ug kg(
      1)). Unlike the peroxide value, acrylamide levels in French fries did not change
      significantly with an increase in the number of frying cycles when tested for 600
      frying cycles for every type of oil. This study clearly indicates that the
      contribution of frying oils to the formation of acrylamide should not be
      neglected due to their different heat transfer coefficients. On the other hand,
      continuous use of frying oil does not lead to a higher acrylamide concentration
      in French fries.

PMID- 25953073
TI  - Canine status epilepticus treated with fosphenytoin: A proof of principle study.
AB  - OBJECTIVES: There are a limited number of marketed intravenous antiepileptic
      drugs (AEDs) available to treat status epilepticus (SE). All were first developed
      for chronic therapy of epilepsy, not specifically for SE. Epilepsy and canine SE
      (CSE) occur naturally in dogs, with prevalence, presentation, and percentage of
      refractory cases similar to human epilepsy. The objective of this study was to
      determine if CSE treated with fosphenytoin (FOS) results in a similar responder
      rate as for people. METHODS: A randomized clinical trial was performed for dogs
      with CSE. Dogs who presented during a seizure or who had additional seizures
      after enrolling received intravenous (i.v.) benzodiazepine (BZD) followed
      immediately by intravenous infusion of 15 mg/kg phenytoin equivalent (PE) of
      fosphenytoin (FOS) or saline placebo (PBO). If seizures continued, additional
      AEDs were administered per the standard of care for veterinary patients. Total
      and unbound plasma phenytoin (PHT) concentrations were measured. RESULTS: Consent
      was obtained for 50 dogs with CSE. Thirty-one had additional motor seizures and
      were randomized to the study intervention (22 FOS and 9 PBO). There was a
      statistically significant difference in the 12 h responder rate, with 63% in the
      FOS group versus 22% in the placebo group (p = 0.043) having no further seizures.
      The unbound PHT concentrations at 30 and 60 min were within the therapeutic
      concentrations for people (1-2 MUg/ml) with the exception of one dog. There was
      mild vomiting in 36% of the FOS group (7/22) within 20 min of FOS administration
      and none of the placebo group (0/9) (p = 0.064). SIGNIFICANCE: This proof of
      concept study provides the first evidence that FOS is tolerated and effective in
      canine SE at PHT concentrations clinically relevant for human SE. Furthermore,
      naturally occurring CSE can be utilized as a translational platform for future
      studies of novel SE compounds.

PMID- 25953075
TI  - Inter-annual changes in detritus-based food chains can enhance plant growth
      response to elevated atmospheric CO2.
AB  - Elevated atmospheric CO2 generally enhances plant growth, but the magnitude of
      the effects depend, in part, on nutrient availability and plant photosynthetic
      pathway. Due to their pivotal role in nutrient cycling, changes in abundance of
      detritivores could influence the effects of elevated atmospheric CO2 on essential
      ecosystem processes, such as decomposition and primary production. We conducted a
      field survey and a microcosm experiment to test the influence of changes in
      detritus-based food chains on litter mass loss and plant growth response to
      elevated atmospheric CO2 using two wetland plants: a C3 sedge (Scirpus olneyi)
      and a C4 grass (Spartina patens). Our field study revealed that organism's
      sensitivity to climate increased with trophic level resulting in strong inter
      annual variation in detritus-based food chain length. Our microcosm experiment
      demonstrated that increased detritivore abundance could not only enhance
      decomposition rates, but also enhance plant growth of S. olneyi in elevated
      atmospheric CO2 conditions. In contrast, we found no evidence that changes in the
      detritus-based food chains influenced the growth of S. patens. Considered
      together, these results emphasize the importance of approaches that unite
      traditionally subdivided food web compartments and plant physiological processes
      to understand inter-annual variation in plant production response to elevated
      atmospheric CO2. 

PMID- 25953076
TI  - Early vaccine availability represents an important public health advance for the
      control of pandemic influenza.
AB  - BACKGROUND: Traditional processes for the production of pandemic influenza
      vaccines are not capable of producing a vaccine that could be deployed sooner
      than 5-6 months after strain identification. Plant-based vaccine technologies are
      of public health interest because they represent an opportunity to begin
      vaccinating earlier. METHODS: We used an age- and risk- structured disease
      transmission model for Canada to evaluate the potential impact of a plant
      produced vaccine available for rapid deployment (within 1-3 months) compared to
      an egg-based vaccine timeline. RESULTS: We found that in the case of a mildly
      transmissible virus (R0 = 1.3), depending on the amount of plant-based vaccine
      produced per week, severe clinical outcomes could be decreased by 60-100 % if
      vaccine was available within 3 months of strain identification. However, in the
      case of a highly transmissible virus (R0 = 2.0), a delay of 3 months does not
      change clinical outcomes regardless of the level of weekly vaccine availability.
      If transmissibility is high, the only strategy that can impact clinical outcomes
      occurs if vaccine production is high and available within 2 months. CONCLUSIONS:
      Pandemic influenza vaccines produced by plants, change the timeline of pandemic
      vaccine availability in a way that could significantly mitigate the impact of the
      next influenza pandemic.

PMID- 25953077
TI  - Movement disorders in systemic lupus erythematosus and antiphospholipid syndrome-
      a video presentation.

PMID- 25953079
TI  - GBIS: the information system of the German Genebank.
AB  - The German Federal ex situ Genebank of Agricultural and Horticultural Crop
      Species is the largest collection of its kind in the countries of the European
      Union and amongst the 10 largest collections worldwide. Beside its enormous
      scientific value as a safeguard of plant biodiversity, the plant genetic
      resources maintained are also of high importance for breeders to provide new
      impulses. The complex processes of managing such a collection are supported by
      the Genebank Information System (GBIS). GBIS is an important source of
      information for researchers and plant breeders, e.g. for identifying appropriate
      germplasm for breeding purposes. In addition, the access to genebank material as
      a sovereign task is also of high interest to the general public. Moreover, GBIS
      acts as a data source for global information systems, such as the Global
      Biodiversity Information Facility (GBIF) or the European Search Catalogue for
      Plant Genetic Resources (EURISCO). Database URL: http://gbis.ipk-gatersleben.de/

PMID- 25953078
TI  - High-throughput screening for modulators of cellular contractile force.
AB  - When cellular contractile forces are central to pathophysiology, these forces
      comprise a logical target of therapy. Nevertheless, existing high-throughput
      screens are limited to upstream signalling intermediates with poorly defined
      relationships to such a physiological endpoint. Using cellular force as the
      target, here we report a new screening technology and demonstrate its
      applications using human airway smooth muscle cells in the context of asthma and
      Schlemm's canal endothelial cells in the context of glaucoma. This approach
      identified several drug candidates for both asthma and glaucoma. We attained
      rates of 1000 compounds per screening day, thus establishing a force-based
      cellular platform for high-throughput drug discovery. 

PMID- 25953080
TI  - CerebralWeb: a Cytoscape.js plug-in to visualize networks stratified by
      subcellular localization.
AB  - CerebralWeb is a light-weight JavaScript plug-in that extends Cytoscape.js to
      enable fast and interactive visualization of molecular interaction networks
      stratified based on subcellular localization or other user-supplied annotation.
      The application is designed to be easily integrated into any website and is
      configurable to support customized network visualization. CerebralWeb also
      supports the automatic retrieval of Cerebral-compatible localizations for human,
      mouse and bovine genes via a web service and enables the automated parsing of
      Cytoscape compatible XGMML network files. CerebralWeb currently supports embedded
      network visualization on the InnateDB (www.innatedb.com) and Allergy and Asthma
      Portal (allergen.innatedb.com) database and analysis resources. Database tool
      URL: http://www.innatedb.com/CerebralWeb

PMID- 25953081
TI  - MIsoMine: a genome-scale high-resolution data portal of expression, function and
      networks at the splice isoform level in the mouse.
AB  - Products of multiexon genes, especially in higher organisms, are a mixture of
      isoforms with different or even opposing functions, and therefore need to be
      treated separately. However, most studies and available resources such as Gene
      Ontology provide only gene-level function annotations, and therefore lose the
      differential information at the isoform level. Here we report MIsoMine, a high
      resolution portal to multiple levels of functional information of alternatively
      spliced isoforms in the mouse. This data portal provides tissue-specific
      expression patterns and co-expression networks, along with such previously
      published functional genomic data as protein domains, predicted isoform-level
      functions and functional relationships. The core utility of MIsoMine is allowing
      users to explore a preprocessed, quality-controlled set of RNA-seq data
      encompassing diverse tissues and cell lineages. Tissue-specific co-expression
      networks were established, allowing a 2D ranking of isoforms and tissues by co
      expression patterns. The results of the multiple isoforms of the same gene are
      presented in parallel to facilitate direct comparison, with cross-talking to
      prioritized functions at the isoform level. MIsoMine provides the first isoform
      level resolution effort at genome-scale. We envision that this data portal will
      be a valuable resource for exploring functional genomic data, and will complement
      the existing functionalities of the mouse genome informatics database and the
      gene expression database for the laboratory mouse. Database URL:
      http://guanlab.ccmb.med.umich.edu/misomine/

PMID- 25953082
TI  - Magnetospinning of Nano- and Microfibers.
AB  - Magnetospinning is a new method for spinning of continuous micro- and nano-fibers
      using a permanent revolving magnet. The method utilizes magnetic forces and the
      hydrodynamic features of stretched threads to produce highly loaded, fine
      magnetic nanofibers. The magnetospinning process is independent of the solution
      dielectric properties and requires no high voltages, in contrast to the more
      traditional electrospinning technique. 

PMID- 25953083
TI  - "Reference rot": does it matter?

PMID- 25953085
TI  - Vagina-hip fistula after tension-free transobturator tape placement.

PMID- 25953084
TI  - Columnar cystic metaplasia in Retzius' space.

PMID- 25953086
TI  - Emotional reactivity to daily stress, spousal emotional support, and fasting
      blood glucose among patients with type 2 diabetes.
AB  - Stress is associated with higher blood glucose in patients with diabetes, but the
      strength of this association varies considerably across patients. The current
      daily diary study of 129 patients with type 2 diabetes examined whether
      individual differences in emotional stress reactivity were associated with
      fasting blood glucose and whether emotional support provided by spouses moderated
      this association. Greater stress reactivity was related to greater variability in
      patients' fasting glucose readings and, among patients with less support, to
      higher fasting glucose levels. Investigating individual differences in emotional
      stress reactivity may help to clarify the role of stress in blood glucose
      control.

PMID- 25953089
TI  - The CBL-CIPK signaling module in plants: a mechanistic perspective.
AB  - In a given environment, plants are constantly exposed to multitudes of stimuli.
      These stimuli are sensed and transduced to generate a diverse array of responses
      by several signal transduction pathways. Calcium (Ca2+ ) signaling is one such
      important pathway involved in transducing a large number of stimuli or signals in
      both animals and plants. Ca2+ engages a plethora of decoders to mediate signaling
      in plants. Among these groups of decoders, the sensor responder complex of
      calcineurin B-like protein (CBL) and CBL-interacting protein kinases (CIPKs) play
      a very significant role in transducing these signals. The signal transduction
      mechanism in most cases is phosphorylation events, but some structural role for
      the pair has also come to light recently. In this review, we discuss the
      structural nature of the sensor-responder duo; their mechanism of substrate
      phosphorylation and also their structural role in modulating targets. Moreover,
      the mechanism of complex formation and mechanistic role of protein phosphatases
      with CBL-CIPK module has been mentioned. A comparison of CBL-CIPK with other
      decoders of Ca2+ signaling in plants also signifies the relatedness and diversity
      in signaling pathways. Further an attempt has been made to compare this aspect of
      Ca2+ signaling pathways in different plant species to develop a holistic
      understanding of conservation of stimulus-response-coupling mediated by this Ca2+
      -CBL-CIPK module.

PMID- 25953088
TI  - Deep, Quantitative Coverage of the Lysine Acetylome Using Novel Anti-acetyl
      lysine Antibodies and an Optimized Proteomic Workflow.
AB  - Introduction of antibodies specific for acetylated lysine has significantly
      improved the detection of endogenous acetylation sites by mass spectrometry.
      Here, we describe a new, commercially available mixture of anti-lysine
      acetylation (Kac) antibodies and show its utility for in-depth profiling of the
      acetylome. Specifically, seven complementary monoclones with high specificity for
      Kac were combined into a final anti-Kac reagent which results in at least a
      twofold increase in identification of Kac peptides over a commonly used Kac
      antibody. We outline optimal antibody usage conditions, effective offline basic
      reversed phase separation, and use of state-of-the-art LC-MS technology for
      achieving unprecedented coverage of the acetylome. The methods were applied to
      quantify acetylation sites in suberoylanilide hydroxamic acid-treated Jurkat
      cells. Over 10,000 Kac peptides from over 3000 Kac proteins were quantified from
      a single stable isotope labeling by amino acids in cell culture labeled sample
      using 7.5 mg of peptide input per state. This constitutes the deepest coverage of
      acetylation sites in quantitative experiments obtained to-date. The approach was
      also applied to breast tumor xenograft samples using isobaric mass tag labeling
      of peptides (iTRAQ4, TMT6 and TMT10-plex reagents) for quantification. Greater
      than 6700 Kac peptides from over 2300 Kac proteins were quantified using 1 mg of
      tumor protein per iTRAQ 4-plex channel. The novel reagents and methods we
      describe here enable quantitative, global acetylome analyses with depth and
      sensitivity approaching that obtained for other well-studied post-translational
      modifications such as phosphorylation and ubiquitylation, and should have
      widespread application in biological and clinical studies employing mass
      spectrometry-based proteomics.

PMID- 25953090
TI  - Decreased serum HDL at initial diagnosis correlates with worse outcomes for
      triple-negative breast cancer but not non-TNBCs.
AB  - PURPOSE: This study aimed to evaluate the associations between metabolic syndrome
      (MS) and its components at initial diagnosis and outcomes of breast cancer
      including triple-negative breast cancer (TNBC) and non-TNBC. METHODS: A cohort of
      1,391 patients was reviewed between January 2004 and July 2008 (including 394
      TNBC and 855 non-TNBC cases). MS and its components including body mass index
      (BMI), serum high-density lipoprotein (HDL) and triglycerides (TG) and their
      relationships with clinical outcomes were analyzed and then compared between
      groups. RESULTS: The incidences of MS and its components including BMI, the
      levels of HDL and TG were not differently distributed between the 2 groups (all
      p's >0.05). However, more TNBC than non-TNBC patients presented with hypertension
      and elevated serum glucose (20.3% vs. 14.9% and 16.0% vs. 10.8%, p = 0.018 and p
      = 0.012, respectively). TNBC patients had poorer 5-year relapse-free survival
      (RFS) than non-TNBC patients (72.8% vs. 84.2%, p<0.0001). Only in the TNBC group,
      patients with low high-density lipoprotein (HDL) demonstrated worse RFS and
      overall survival (OS; p<0.0001). Multivariate analysis identified that low HDL
      was an independent worse prognostic factor for both RFS (hazard ratio [HR] =
      3.266, 95% confidence interval [95%CI], 2.087-5.112, p<0.0001) and OS (HR =
      3.071, 95%CI, 1.732-5.445, p<0.0001) in TNBC patients. CONCLUSIONS: Decreased
      level of HDL may predict worse outcomes both in terms of RFS and OS for TNBC
      patients but not for non-TNBC patients. Further investigations are warranted to
      detect the underlying mechanisms.

PMID- 25953087
TI  - Activating PIK3CA Mutations Induce an Epidermal Growth Factor Receptor
      (EGFR)/Extracellular Signal-regulated Kinase (ERK) Paracrine Signaling Axis in
      Basal-like Breast Cancer.
AB  - Mutations in PIK3CA, the gene encoding the p110alpha catalytic subunit of
      phosphoinositide 3-kinase (PI3K) have been shown to transform human mammary
      epithelial cells (MECs). These mutations are present in all breast cancer
      subtypes, including basal-like breast cancer (BLBC). Using liquid chromatography
      tandem mass spectrometry (LC-MS/MS), we identified 72 protein expression changes
      in human basal-like MECs with knock-in E545K or H1047R PIK3CA mutations versus
      isogenic MECs with wild-type PIK3CA. Several of these were secreted proteins,
      cell surface receptors or ECM interacting molecules and were required for growth
      of PIK3CA mutant cells as well as adjacent cells with wild-type PIK3CA. The
      proteins identified by MS were enriched among human BLBC cell lines and pointed
      to a PI3K-dependent amphiregulin/EGFR/ERK signaling axis that is activated in
      BLBC. Proteins induced by PIK3CA mutations correlated with EGFR signaling and
      reduced relapse-free survival in BLBC. Treatment with EGFR inhibitors reduced
      growth of PIK3CA mutant BLBC cell lines and murine mammary tumors driven by a
      PIK3CA mutant transgene, all together suggesting that PIK3CA mutations promote
      tumor growth in part by inducing protein changes that activate EGFR. 

PMID- 25953091
TI  - The extracellular protease stl functions to inhibit migration of v'ch1 sensory
      neuron during Drosophila embryogenesis.
AB  - Proper migration of cells through the dense and complex extracellular matrix
      (ECM) requires constant restructuring of the ECM to allow cells to move forward
      in a smooth manner. This restructuring can occur through the action of
      extracellular enzymes. Among these extracellular enzymes is the ADAMTS (A
      Disintegrin And Metalloprotease with ThromboSpondin repeats) family of secreted
      extracellular proteases. Drosophila stl encodes an ADAMTS protease expressed in
      and around the peripheral nervous system (PNS) during embryogenesis. The absence
      of stl displayed one specific neuron, the v'ch1 sensory neuron, migrating to its
      target sooner than in wild type. During normal development, the v'ch1 sensory
      neuron migrates dorsally at the same time it is extending an axon ventrally
      toward the CNS. Surprisingly, in the absence of stl, the v'ch1 neuron migrated
      further dorsally as compared to the wild type at stage 15, but did not migrate
      past its correct target at stage 16, suggesting a novel role for this
      extracellular protease in inhibiting migration of this neuron past a certain
      point. 

PMID- 25953092
TI  - Ictal analgesia in temporal lobe epilepsy - The mechanism of seizure-related
      burns.
AB  - Seizure-related injuries have major impact in the excess mortality and morbidity
      of epilepsy patients. Experimental data suggest that analgesia may develop during
      seizures contributing to the severity of seizure-related accidents, especially
      burns. We aimed to identify those seizure-types that may lead to burn-injuries by
      seizure-related analgesia. In our tertiary epilepsy centre, we asked 100 epilepsy
      patients having a history of seizure-related injury, to complete our burn-and
      pain questionnaire. Fifty-one patients completed the survey; their epileptology
      data were collected and those with a seizure-related burn were interviewed. Forty
      two out of the 51 patients (82%) had partial epilepsy and 9 (18%) had idiopathic
      generalised epilepsy. Twenty-six persons (51%) reported decreased pain perception
      during or after seizures in general. Twelve patients (23%) had suffered one or
      more seizure-related burn. Five of them fell onto a hot surface or fire
      accidentally, during generalized tonic-clonic seizures. Seven out of the 12 burnt
      patients (58%) grasped a hot object or reached into boiling fluid during complex
      partial seizures; without experiencing-, or reacting in response to pain. These
      patients had temporal lobe epilepsy, 5 of them had left temporal seizure onset.
      Our hypothesis based on the circumstantial analysis of our patients' burn
      injuries; is that temporal lobe seizures may cause ictal/postictal analgesia. It
      may be caused by the seizure-related epileptic facilitation of the periaqueductal
      gray matter; the central pain-inhibiting structure of the brain. Seizure-related
      endogenous opioid-release my have a contributory role in inhibiting pain
      perception. Ictal analgesia warrants better burn-prevention in temporal lobe
      epilepsy patients. Understanding the mechanism of ictal analgesia and specifying
      those seizures-types prone to cause it; may help indentifying human pain
      inhibiting pathways. 

PMID- 25953094
TI  - Pediatric neurosurgery at British Columbia's Children's Hospital.

PMID- 25953093
TI  - Comparison of outcomes after 3-month methadone maintenance treatment between
      heroin users with and without HIV infection: a 3-month follow-up study.
AB  - BACKGROUND: The aim of this study was to compare the changes in primary (heroin
      use-related) and secondary (depressive symptoms and quality of life, QOL) outcome
      indicators of 3-month methadone maintenance treatment (MMT) between heroin users
      with and without HIV infection. METHODS: A total of 242 intravenous heroin
      dependent individuals (30 with and 212 without HIV infection) receiving MMT were
      recruited. Primary (severity of heroin dependence, harm caused by heroin use and
      current heroin use) and secondary (depressive symptoms and QOL) outcome
      indicators were determined before and after receiving 3-month MMT. Changes in
      primary and secondary outcome indicators between the two groups were compared
      using mixed-model analysis. RESULTS: Heroin users both with and without HIV
      infection showed significant improvement in three primary outcome indicators
      after 3-month MMT, and there was no difference in the changes of these primary
      outcome indicators between the two groups. However, improvements in depressive
      symptoms and the physical domain of QOL among HIV-infected heroin users were
      poorer than in those without HIV infection. CONCLUSIONS: The results of this
      study indicated that heroin users with HIV infection did improve in the primary
      but not the secondary outcomes after 3-month MMT.

PMID- 25953095
TI  - Modified pedicle subtraction osteotomies (mPSO) for thoracolumbar post-tubercular
      kyphosis in pediatric patients: retrospective clinical cases and review of the
      literature.
AB  - PURPOSE: The purpose of this study was to evaluate the clinical and radiographic
      outcomes of modified pedicle subtraction osteotomy (mPSO) for thoracolumbar post
      tubercular kyphosis in pediatric patients. METHODS: From January 2008 to August
      2012, 26 consecutive pediatric patients with thoracolumbar post-tubercular
      kyphosis underwent modified pedicle subtraction osteotomy (mPSO). The clinical
      and radiologic outcomes were analyzed preoperatively, postoperatively, and at the
      last follow-up. RESULTS: Twenty-six patients with thoracolumbar post-tubercular
      kyphosis underwent mPSO. The average operation time was 256 min (188~314 min).
      The mean follow-up was 41 months (18~56 months). The mean estimated blood loss
      was 870 ml (620 ~ 1020 ml). The thoracolumbar kyphotic angle ranged from 51
      degrees  to 79 degrees  before operation, 60.6 degrees  in average. The mean
      thoracolumbar kyphotic Cobb angle was 19.7 degrees  after operation, with a mean
      correction of 40.9 degrees . The C7 sagittal plumb line was 3.8 cm after
      operation, comparing to the 10.5 cm preoperative. The mean preoperative angle of
      thoracic kyphosis (TK) was 9.9 degrees  +/- 1.2 degrees  and increased to 11.8
      degrees  +/- 1.4 degrees , postoperatively. Lumbar lordosis (LL) improved from 
      22.8 degrees  +/- 4.9 degrees  preoperative to -17.8 degrees  +/- 2.1 degrees 
      postoperative. Visual analogue scale (VAS) was 8.7 +/- 1.1 preoperative and 1.2
      +/- 0.4 postoperative, respectively. The mean Oswestry Disability Index (ODI)
      improved from 49.2 +/- 5.3 before surgery to 10.8 +/- 3.3 postoperative (P <
      0.01). All patients received good bone healing, no significant loss of correction
      angle. Most patients (24/26) considered pain and exterior was significantly
      improved. CONCLUSION: Modified pedicle subtraction osteotomy (mPSO) is effective
      and reliable for thoracolumbar post-tubercular kyphosis in pediatric patients.

PMID- 25953096
TI  - Investigation of the location of atypical teratoid/rhabdoid tumor.
AB  - INTRODUCTION: The location of a brain tumor is a fundamental characteristic,
      because various brain tumors develop in relatively specific locations. An
      atypical teratoid/rhabdoid tumor (AT/RT) is a highly age-specific tumor that
      occurs in infants and young children. However, AT/RTs develop in a variety of
      locations in the brain. This study aimed at uncovering the tumor location pattern
      of AT/RTs to enhance diagnoses. MATERIAL AND METHODS: Neuroimages from 27
      patients with a pathologically proven AT/RT were reviewed, and the specific tumor
      locations were described and categorized. The association of imaging
      characteristics and tumor location was analyzed. RESULTS: The posterior fossa was
      the most frequent locations accounting for 19 patients (70%), followed by the
      diencephalon (four patients; 15%), cerebrum (three patients; 11%), and midbrain
      (one patient; 4%). In the posterior fossa, the superior medullary velum (SMV) and
      cerebellopontine angle (CPA) areas were the most common sites (eight patients
      each) and three patients had a tumor in the inferior medullary velum (IMV)
      region. AT/RTs in the SMV area had a significantly higher chance of no/minimal
      enhancement compared with tumors in other locations (P = 0.001) and a lower
      likelihood of leptomeningeal tumor seeding at presentation (P = 0.053).
      CONCLUSION: The location spectrum of AT/RT follows a specific pattern, and some
      of the locations are linked with intriguing clinical characteristics. This
      information may not only help make correct preoperative diagnosis but also
      occasionally aid in postoperative pathological diagnosis.

PMID- 25953097
TI  - Pneumocephalus after endoscopic odontoidectomy in a pediatric patient: the lesson
      learned.
AB  - INTRODUCTION: Postoperative pneumocephalus is an unexpected condition after
      endoscopic odontoidectomy surgery. CASE: We present the first case of
      pneumocephalus after odontoidectomy in a pediatric patient. The clinical
      presentation, radiological findings, and surgical procedures are described with
      related pathophysiology. CONCLUSION: We outline the key for management of a rare
      intracranial air entrapment case after an endoscopic odontoidectomy surgery in a
      pediatric patient and the measures taken to prevent its occurrence in the future.

PMID- 25953098
TI  - Carbon dioxide field flooding reduces the hemodynamic effects of venous air
      embolism occurring in the sitting position.
AB  - PURPOSE: Although the utility of the sitting position is undisputed for
      biomechanical and ergonomic reasons, it has been debated in recent years for its
      risks, particularly venous air embolism (VAE). In order to reduce the hemodynamic
      effect of VAE, we changed the composition of the surgical field air partially
      replacing nitrogen with carbon dioxide (CO2) that better dissolves in human
      tissues. METHODS: First, we tested our method on a test dummy in the sitting
      position. Infrared CO2 sensors were placed close to the wound opening and on the
      facial mask of the surgeon. An oxygen sensor was connected to a computer for data
      recording (ALTAIR((r)), MSA Safety). This model showed that 10 L/min CO2 flow
      provides efficient air displacement, maintaining safety for the surgeon. We
      reproduced the above-described surgical field environment in ten consecutive
      cases of posterior fossa surgery performed in the sitting position. A homogeneous
      group of ten patients operated in the sitting position with standard setting
      environment was used for control. We intraoperatively monitored VAE with trans
      esophageal echocardiography (TEE), end-tidal CO2 (ETCO2), CO2 arterial pressure
      (PaCO2), and hemodynamic changes. RESULTS: Although the percentage of VAE was 70%
      in both groups, hemodynamic effects occurred in 10% of cases in the study group
      and in 40% of cases in the control group. CONCLUSIONS: Our preliminary study
      shows that a CO2-enriched sitting position surgical microenvironment
      significantly reduces the hemodynamic effects of VAE, more likely because
      arterial CO2 emboli are more soluble and consequently much better tolerated than
      air emboli.

PMID- 25953099
TI  - Familial and neighborhood effects on psychiatric disorders in childhood and
      adolescence.
AB  - BACKGROUND: More knowledge is needed on potential associations between individual
      , family-, and neighborhood-level factors and psychiatric disorders in children
      and adolescents. AIMS: To examine associations between, individual-, family-, and
      neighborhood-level factors and incident internalizing (anxiety and mood)
      disorders and externalizing (ADHD and conduct) disorders in children and
      adolescents, and to estimate the relative contributions of family and
      neighborhood to individual variation in these disorders. METHOD: We performed a
      three-level logistic regression on all 542,195 children born in Sweden in 1992
      1996, nested in 427,954 families, which in turn were nested in 8475
      neighborhoods. The children were followed from 2000 to 2010 for incident
      internalizing and externalizing psychiatric disorders, assessed from medical
      records. RESULTS: 26,514 children (4.8%) were diagnosed with internalizing or
      externalizing psychiatric disorders. Approximately 29% of the total individual
      variance in internalizing disorders could be attributed to the family level,
      which includes both genetic and family environmental effects, and 5% to the
      neighborhood level. The corresponding figures for externalizing disorders were
      43.5% and 5.5%, respectively. After adjustment for individual-level
      sociodemographic factors, high neighborhood deprivation was associated with
      increased risks of externalizing and internalizing psychiatric disorders (odds
      ratio [OR] = 1.37, 95% credible interval [CI] = 1.25-1.50 and OR = 1.34, 95% CI =
      1.25-1.45, respectively), including conduct disorder (OR = 2.01, 95% CI = 1.58
      2.55), anxiety disorders (OR = 1.40, 95% CI = 1.29-1.52), and mood disorders (OR
      = 1.21, 95% CI, 1.09-1.35). The strongest association between neighborhood
      deprivation and ADHD was observed in moderately deprived neighborhoods (OR =
      1.31, 95% CI = 1.19-1.44). CONCLUSIONS: These findings call for policies to
      promote mental health that consider potential influences from children's family
      and neighborhood environments.conclusion TRIAL REGISTRATION: Not applicable.

PMID- 25953100
TI  - Evaluating transition state structures of vanadium-phosphatase protein complexes
      using shape analysis.
AB  - Shape analysis of coordination complexes is well-suited to evaluate the subtle
      distortions in the trigonal bipyramidal (TBPY-5) geometry of vanadium coordinated
      in the active site of phosphatases and characterized by X-ray crystallography.
      Recent studies using the tau (tau) analysis support the assertion that vanadium
      is best described as a trigonal bipyramid, because this geometry is the ideal
      transition state geometry of the phosphate ester substrate hydrolysis (C.C.
      McLauchlan, B.J. Peters, G.R. Willsky, D.C. Crans, Coord. Chem. Rev.
      http://dx.doi.org/10.1016/j.ccr.2014.12.012 ; D.C. Crans, M.L. Tarlton, C.C.
      McLauchlan, Eur. J. Inorg. Chem. 2014, 4450-4468). Here we use continuous shape
      measures (CShM) analysis to investigate the structural space of the five
      coordinate vanadium-phosphatase complexes associated with mechanistic
      transformations between the tetrahedral geometry and the five-coordinate high
      energy TBPY-5 geometry was discussed focusing on the protein tyrosine phosphatase
      1B (PTP1B) enzyme. No evidence for square pyramidal geometries was observed in
      any vanadium-protein complexes. The shape analysis positioned the metal ion and
      the ligands in the active site reflecting the mechanism of the cleavage of the
      organic phosphate in a phosphatase. We identified the umbrella distortions to be
      directly on the reaction path between tetrahedral phosphate and the TBPY-5-types
      of high-energy species. The umbrella distortions of the trigonal bipyramid are
      therefore identified as being the most relevant types of transition state
      structures for the phosphoryl group transfer reactions for phosphatases and this
      may be related to the possibility that vanadium is an inhibitor for enzymes that
      support both exploded and five-coordinate transition states. 

PMID- 25953101
TI  - Catheter Ablation of Premature Ventricular Contractions Originating in the Aortic
      Sinus Cusp or Great Cardiac Vein: Two QRS Morphologies with One Origin.
AB  - BACKGROUND: Premature ventricular contractions (PVCs) originating from aortic
      sinus cusps (ASCs) can exhibit preferential conduction to right ventricular
      outflow tract (RVOT). OBJECTIVES: This study aimed to examine the
      electrophysiological characteristics for guiding catheter ablation in patients
      with two morphological types of PVCs that originate from ASCs or the great
      cardiac vein (GCV). METHODS: We analyzed electrocardiogram from 10 patients with
      PVCs of two QRS morphologies. The patients who exhibited dominant left bundle
      branch block (LBBB) QRS morphology and less right bundle branch block (RBBB)
      morphology were designated as group 1 (n = 7), and those with dominant RBBB QRS
      morphology were designated as group 2 (n = 3). During PVCs, electroanatomical
      mapping was performed in both RVOT and ASC in group 1 and only performed in ASC
      or GCV in group 2. RESULTS: In group 1, the earliest ventricular activation
      preceding the onset of the QRS complex (V-QRS) was recorded for 27 +/- 6 ms
      (range 18-36 ms) in RVOT and 25 +/- 6 ms (range 18-34 ms) in the ASC, while V-QRS
      was recorded for 28 ms, 42 ms, 40 ms in the ASC or GCV in group 2. All patients
      were successfully ablated at one site finally, including left coronary cusp in
      seven, left-right coronary cusp commissure in two, and GCV in one. None of the
      patients experienced recurrence or complications during the 18.4 +/- 5.1 (range 6
      24 months) months of follow-up. CONCLUSIONS: Two QRS morphologies (LBBB and RBBB
      with inferior axis) in PVCs could be a predictor of PVCs originating from ASC or
      GCV.

PMID- 25953102
TI  - Azacytidine sensitizes acute myeloid leukemia cells to arsenic trioxide by up
      regulating the arsenic transporter aquaglyceroporin 9.
AB  - BACKGROUND: The therapeutic efficacy of arsenic trioxide (As2O3) in acute myeloid
      leukemia (AML) is modest, which is partly related to its limited intracellular
      uptake into the leukemic cells. As2O3 enters cells via the transmembrane protein
      aquaglyceroporin 9 (AQP9). Azacytidine, a demethylating agent that is approved
      for the treatment of AML, has been shown to have synergistic effect with As2O3.
      We tested the hypothesis that azacytidine might up-regulate AQP9 and enhances
      As2O3-mediated cytotoxicity in AML. METHODS: Arsenic-induced cytotoxicity, the
      expression of AQP9, and the intracellular uptake of As2O3 were determined in AML
      cell lines and primary AML cells with or without azacytidine pre-treatment. The
      mechanism of AQP9 up-regulation was then investigated by examining the expression
      of transcription factors for AQP9 gene and the methylation status of their gene
      promoters. RESULTS: As2O3-induced cytotoxicity in AML cell lines was
      significantly enhanced after azacytidine pre-treatment as a result of AQP9 up
      regulation, leading to increased arsenic uptake and hence intracellular
      concentration. Blocking AQP9-mediated As2O3 uptake with mercury chloride
      abrogated the sensitization effect of azacytidine. AQP9 promoter does not contain
      CpG islands. Instead, azacytidine pre-treatment led to increased expression of
      HNF1A, a transcription activator of AQP9, through demethylation of HNF1A
      promoter. HNF1 knockdown abrogated azacytidine-induced AQP9 up-regulation and
      almost completely blocked intracellular As2O3 entry, confirming that azacytidine
      enhanced As2O3-mediated cell death via up-regulation of HNF1A and hence increased
      AQP9 and As2O3 intracellular concentration. Azacytidine sensitization to As2O3
      treatment was re-capitulated also in primary AML samples. Finally, azacytidine
      did not enhance arsenic toxicity in a liver cell line, where HNF1A was largely
      unmethylated. CONCLUSIONS: Azacytidine sensitizes AML cells to As2O3 treatment,
      and our results provide proof-of-principle evidence that pharmacological up
      regulation of AQP9 potentially expands the therapeutic spectrum of As2O3. Further
      clinical trial should evaluate the efficacy of azacytidine in combination with
      As2O3 in the treatment of AML.

PMID- 25953104
TI  - TRANSCRIPTION ACTIVATOR-LIKE EFFECTOR NUCLEASE-Mediated Generation and Metabolic
      Analysis of Camalexin-Deficient cyp71a12 cyp71a13 Double Knockout Lines.
AB  - In Arabidopsis (Arabidopsis thaliana), a number of defense-related metabolites
      are synthesized via indole-3-acetonitrile (IAN), including camalexin and indole-3
      carboxylic acid (ICOOH) derivatives. Cytochrome P450 71A13 (CYP71A13) is a key
      enzyme for camalexin biosynthesis and catalyzes the conversion of indole-3
      acetaldoxime (IAOx) to IAN. The CYP71A13 gene is located in tandem with its close
      homolog CYP71A12, also encoding an IAOx dehydratase. However, for CYP71A12,
      indole-3-carbaldehyde and cyanide were identified as major reaction products. To
      clarify CYP71A12 function in vivo and to better understand IAN metabolism, we
      generated two cyp71a12 cyp71a13 double knockout mutant lines. CYP71A12-specific
      transcription activator-like effector nucleases were introduced into the cyp71a13
      background, and very efficient somatic mutagenesis was achieved. We observed
      stable transmission of the cyp71a12 mutation to the following generations, which
      is a major challenge for targeted mutagenesis in Arabidopsis. In contrast to
      cyp71a13 plants, in which camalexin accumulation is partially reduced, double
      mutants synthesized only traces of camalexin, demonstrating that CYP71A12
      contributes to camalexin biosynthesis in leaf tissue. A major role of CYP71A12
      was identified for the inducible biosynthesis of ICOOH. Specifically, the ICOOH
      methyl ester was reduced to 12% of the wild-type level in AgNO3-challenged
      cyp71a12 leaves. In contrast, indole-3-carbaldehyde derivatives apparently are
      synthesized via alternative pathways, such as the degradation of indole
      glucosinolates. Based on these results, we present a model for this surprisingly
      complex metabolic network with multiple IAN sources and channeling of IAOx
      derived IAN into camalexin biosynthesis. In conclusion, transcription activator
      like effector nuclease-mediated mutation is a powerful tool for functional
      analysis of tandem genes in secondary metabolism. 

PMID- 25953103
TI  - Transcription Factor ATAF1 in Arabidopsis Promotes Senescence by Direct
      Regulation of Key Chloroplast Maintenance and Senescence Transcriptional
      Cascades.
AB  - Senescence represents a fundamental process of late leaf development.
      Transcription factors (TFs) play an important role for expression reprogramming
      during senescence; however, the gene regulatory networks through which they exert
      their functions, and their physiological integration, are still largely unknown.
      Here, we identify the Arabidopsis (Arabidopsis thaliana) abscisic acid (ABA)- and
      hydrogen peroxide-activated TF Arabidopsis thaliana activating factor1 (ATAF1) as
      a novel upstream regulator of senescence. ATAF1 executes its physiological role
      by affecting both key chloroplast maintenance and senescence-promoting TFs,
      namely GOLDEN2-LIKE1 (GLK1) and ORESARA1 (Arabidopsis NAC092), respectively.
      Notably, while ATAF1 activates ORESARA1, it represses GLK1 expression by directly
      binding to their promoters, thereby generating a transcriptional output that
      shifts the physiological balance toward the progression of senescence. We
      furthermore demonstrate a key role of ATAF1 for ABA- and hydrogen peroxide
      induced senescence, in accordance with a direct regulatory effect on ABA
      homeostasis genes, including nine-CIS-epoxycarotenoid dioxygenase3 involved in
      ABA biosynthesis and ABC transporter G family member40, encoding an ABA transport
      protein. Thus, ATAF1 serves as a core transcriptional activator of senescence by
      coupling stress-related signaling with photosynthesis- and senescence-related
      transcriptional cascades.

PMID- 25953105
TI  - Perovskite-fullerene hybrid materials suppress hysteresis in planar diodes.
AB  - Solution-processed planar perovskite devices are highly desirable in a wide
      variety of optoelectronic applications; however, they are prone to hysteresis and
      current instabilities. Here we report the first perovskite-PCBM hybrid solid with
      significantly reduced hysteresis and recombination loss achieved in a single
      step. This new material displays an efficient electrically coupled
      microstructure: PCBM is homogeneously distributed throughout the film at
      perovskite grain boundaries. The PCBM passivates the key PbI3(-) antisite defects
      during the perovskite self-assembly, as revealed by theory and experiment.
      Photoluminescence transient spectroscopy proves that the PCBM phase promotes
      electron extraction. We showcase this mixed material in planar solar cells that
      feature low hysteresis and enhanced photovoltage. Using conductive AFM studies,
      we reveal the memristive properties of perovskite films. We close by positing
      that PCBM, by tying up both halide-rich antisites and unincorporated halides,
      reduces electric field-induced anion migration that may give rise to hysteresis
      and unstable diode behaviour. 

PMID- 25953107
TI  - Perioperative sclerotherapy. A survey of current practice by Italian
      phlebologically-active physicians.
AB  - AIM: To find out how and when Italian phlebologically-active physicians apply
      perioperative sclerotherapy. MATERIAL AND METHODS: A questionnaire was e-mailed
      to the members of three different Italian Societies of Phlebology. The answers
      were collected in a database (SPSS19 for Windows) and statistically evaluated.
      RESULTS: Ninety surgeons (87.4%) and 13 (12.6%) phlebologists responded, 57
      (56,3%) worked in hospital and 46 (44.7%) in an outpatient clinic. Perioperative
      sclerotherapy is administred by 63,1% of respondents merely postoperatively.
      28,2% use also postoperative sclerotherapy, but sometimes in combination with
      preoperative (6.8%) or intraoperative sclerotherapy (21.4%). Only 8,7% perform
      the perioperative sclerotherapy pre-, intra- and/or postoperatively.
      Postoperative sclerotherapy is programmed in a significantly higher percentage
      and earlier in private practice. Vascular surgeons performed intraoperative
      sclerotherapy in a significantly higher percentage in comparison to non-vascular
      surgeons . DISCUSSION: In contrast to the results of British and Irish surveys,
      Italian phlebologically-active physicians perform a remarkably higher percentage
      of perioperative sclerotherapy. Postoperative sclerotherapy is administered after
      2,3+/-1,9 months. Private practitioners sclerose significantly earlier and more
      often compared to the in hospital operators. Postoperative sclerotherapy can be
      considered an adjuvant therapy in order to improve the surgical result and may be
      called "adjuvant sclerotherapy" in order to distinguish it from "sclerosurgery"
      or " sclerostripping", which are performed intraoperatively. CONCLUSIONS: The
      answers of 103 partecipants give an acceptable overview on the current behavior
      of phlebologicallyactive physicians in private and public practice, in Italy.
      Perioperative sclerotherapy seems widely used, mainly as postoperative
      sclerotherapy, but also as sclerosurgery and more seldom as adjuvant
      sclerotherapy, and may lead varicose vein surgery to more miniinvasiveness. The
      rationale of "sclerosurgery" is manifold.

PMID- 25953108
TI  - Beyond the discourse of reproductive choice: narratives of pregnancy resolution
      among Latina/o teenage parents.
AB  - Despite the fact that the US teenage birth rate has declined dramatically in
      recent years, teen births among Latinas are higher than any other racial/ethnic
      group. Most studies focus on the causes and consequences of early motherhood
      among Latina teenagers, neglecting other important dimensions of the issue. This
      study examines how Latina/o teenage parents living in California narrate their
      experiences with unintended pregnancy resolution. Qualitative analysis reveals
      three central themes. First, participants expressed shock upon learning they or
      their partner was pregnant, followed by acceptance about their impending
      parenthood. Second, participants' views of abortion and adoption largely
      foreclosed these options as pathways by which to resolve their unintended
      pregnancies. Third, participants recounted numerous stories of the messages they
      received from parents, other family members and male partners that were
      frequently directive regarding how to resolve their pregnancies. These findings
      have implications for young people's reproductive health and rights, and for
      reproductive justice more broadly. 

PMID- 25953106
TI  - Cortical thickness in adolescent marijuana and alcohol users: A three-year
      prospective study from adolescence to young adulthood.
AB  - Studies suggest marijuana impacts gray and white matter neural tissue
      development, however few prospective studies have determined the relationship
      between cortical thickness and cannabis use spanning adolescence to young
      adulthood. This study aimed to understand how heavy marijuana use influences
      cortical thickness trajectories across adolescence. Subjects were adolescents
      with heavy marijuana use and concomitant alcohol use (MJ+ALC, n=30) and controls
      (CON, n=38) with limited substance use histories. Participants underwent magnetic
      resonance imaging and comprehensive substance use assessment at three independent
      time points. Repeated measures analysis of covariance was used to look at main
      effects of group, time, and Group * Time interactions on cortical thickness.
      MJ+ALC showed thicker cortical estimates across the brain (23 regions),
      particularly in frontal and parietal lobes (ps<.05). More cumulative marijuana
      use was associated with increased thickness estimates by 3-year follow-up
      (ps<.05). Heavy marijuana use during adolescence and into young adulthood may be
      associated with altered neural tissue development and interference with
      neuromaturation that can have neurobehavioral consequences. Continued follow-up
      of adolescent marijuana users will help understand ongoing neural changes that
      are associated with development of problematic use into adulthood, as well as
      potential for neural recovery with cessation of use.

PMID- 25953109
TI  - IRB practices and policies regarding the secondary research use of biospecimens.
AB  - BACKGROUND: As sharing and secondary research use of biospecimens increases, IRBs
      and researchers face the challenge of protecting and respecting donors without
      comprehensive regulations addressing the human subject protection issues posed by
      biobanking. Variation in IRB biobanking policies about these issues has not been
      well documented. METHODS: This paper reports on data from a survey of IRB
      Administrative Directors from 60 institutions affiliated with the Clinical and
      Translation Science Awards (CTSAs) about their policies and practices regarding
      secondary use and sharing of biospecimens. Specifically, IRB ADs were asked about
      consent for future use of biospecimens, assignment of risk for studies using
      biobanked specimens, and sharing of biospecimens/data. RESULTS: Our data indicate
      that IRBs take varying approaches to protocol review, risk assessment, and data
      sharing, especially when specimens are not anonymized. CONCLUSION: Unclear or
      divergent policies regarding biospecimen research among IRBs may constitute a
      barrier to advancing genetic studies and to inter-institutional collaboration,
      given different institutional requirements for human subjects protections.

PMID- 25953110
TI  - Jejunal obstruction due to a variant of transmesocolic hernia: a rare
      presentation of an acute abdomen.
AB  - BACKGROUND: Internal hernias include paraduodenal, pericecal, through foramen of
      Winslow, intersigmoid and retroanastomotic hernias. These hernias could be either
      congenital or acquired after abdominal surgery. They account for approximately
      0.5-5 % of all cases of intestinal obstruction. CASE PRESENTATION: A 48-year-old
      female was admitted to casualty with a history of abdominal distension and
      vomiting of 3 days duration. An abdominal X-ray supine film showed multiple small
      bowel loops with air fluid levels. On surgery she was found to have a
      transmesocolic hernia. The defect in the transverse mesocolon was repaired.
      CONCLUSION: The clinical signs and symptoms of lesser sac hernia are non
      specific. These rare lesser sac hernias can be lethal. Therefore, immediate
      diagnosis and surgery is essential. Although a rare entity, they account for
      significant mortality form intestinal obstruction. We report an extremely rare
      case of an internal abdominal hernia through the transverse mesocolon, in a young
      woman.

PMID- 25953111
TI  - Nodular amyloidosis at the sites of insulin injections.
AB  - Amyloid is characterized by its fibrillary ultrastructure, and more than 20
      proteins have been described to date as possible precursors. Among them, insulin
      and enfuvirtide represent the only medications described as amyloidogenic
      substances. We describe two diabetic patients, who were undergoing long-standing
      subcutaneous insulin treatment, who developed subcutaneous nodules at the sites
      of insulin injections. Histopathologic examination showed the presence of
      eosinophilic and amorphous masses in deep dermis, which stained positive with
      Congo red, amyloid P substance and anti-human insulin antibody. Whether the type
      of injected insulin played a role or not in the pathogenesis of the process is
      still uncertain, because all described patients used both fast-acting and slow
      acting insulins at the same injection sites. Our second case showed nodular
      insulin-derived amyloid tumors only at the sites where exclusively fast-acting
      insulin was injected, which supports the notion that fast-acting insulin may also
      be the cause of this disorder. Insulin-derived nodular amyloidosis is probably
      underdiagnosed because of the small body of literature in comparison with the
      prevalence of insulin dependent diabetic patients. This underdiagnosis probably
      is because of its clinical similarity with the lesions of lipohypertrophy at the
      sites of insulin injections, which is rarely biopsied. 

PMID- 25953112
TI  - Comparison of everolimus- and paclitaxel-eluting stents in dialysis patients.
AB  - BACKGROUND: We previously reported that the incidence of 1-year major adverse
      cardiac events (MACE) in patients treated with paclitaxel-eluting stents (PES)
      was lower than that in the sirolimus-eluting stents in dialysis patients.
      However, it remains unclear whether there are differences in clinical outcomes
      between everolimus-eluting stents (EES) and PES. METHODS: Between February 2010
      and September 2013, 102 maintenance dialysis patients with 135 lesions treated
      with EES were compared to 107 maintenance dialysis patients with 147 lesions
      treated with PES. One-year clinical outcomes were investigated. RESULTS: Diabetes
      mellitus was present in 64.7% in the EES group and 71.0% in the PES group (p =
      0.33). Heavy calcification was in 27.4% vs. 34.0% (p = 0.23). Rotational
      atherectomy was undergone in 11.1% vs. 23.1% (p < 0.01). Total stented length was
      not significantly different (23.5 +/- 14.6 mm vs. 24.4 +/- 13.2 mm, p = 0.60).
      One patient in the EES group was lost to follow up. At 12 months, MACE occurred
      in 13.2% in the EES group and 17.4% in the PES group (p = 0.25). Target lesion
      revascularization (TLR) was observed in 9.5% vs. 10.4% respectively (p = 0.77).
      Mortality was 11.8% vs. 13.1% (p = 0.35). Cardiac death was 5.0% vs. 7.7% (p =
      0.09). Definite stent thrombosis was observed in 2.0% vs. 0% (p = 0.14). Subgroup
      analysis in patients with diabetes mellitus revealed no significant differences
      in MACE (12.7% vs. 14.9%, p = 0.36), TLR (8.3% vs. 7.4%, p = 0.42), mortality
      (13.7% vs. 13.2%, p = 0.28), and cardiac death (6.3% vs. 8.0%, p = 0.15) between
      the two groups. CONCLUSIONS: One-year clinical outcomes following EES and PES
      implantations are similar in dialysis patients.

PMID- 25953113
TI  - Anomalous right coronary artery: case series and review of literature.
AB  - Anomalous right coronary arteries (ARCA) are extremely rare in general
      population. Although mostly asymptomatic and recognized incidentally on cardiac
      catheterizations, they can be catastrophic and can cause sudden cardiac death.
      Sudden cardiac deaths are more common when the anomalous vessel runs an inter
      arterial course between the aorta and the pulmonary artery. Asymptomatic patients
      with malignant course of anomalous coronaries can pose clinical dilemmas. Based
      on prior experience, management of asymptomatic ARCA with malignant course should
      be subjected to a risk-benefit analysis. This case series begins with a brief
      description of four separate cases of ARCA. They had their origin in the left
      coronary sinus or off left anterior descending artery (LAD). Three of them had
      anterior course between aorta and pulmonary trunk, confirmed by coronary CT
      angiography (CTA). Whereas two of our patients presented with chronic symptoms,
      two presented as acute cases with electrocardiographically proven STEMI. These
      cases were managed differently; by conservative, surgical or interventional
      approaches. All four cases had good final outcomes. This goes to show how
      different treatment options can be employed in management of complications
      associated with anomalous coronary arteries. It is also interesting to note that
      the radial access provides better guide support that is needed to tackle complex
      lesions. Many operators have been using radial approach for anomalous coronary
      interventions. We have successfully employed radial technique after failed trans
      femoral attempts and also in STEMI situations. Based on our experience, right
      radial approach appears to be safer and quicker.

PMID- 25953114
TI  - Attraction of egg-killing parasitoids toward induced plant volatiles in a multi
      herbivore context.
AB  - In response to insect herbivory, plants emit volatile organic compounds which may
      act as indirect plant defenses by attracting natural enemies of the attacking
      herbivore. In nature, plants are often attacked by multiple herbivores, but the
      majority of studies which have investigated indirect plant defenses to date have
      focused on the recruitment of different parasitoid species in a single-herbivore
      context. Here, we report our investigation on the attraction of egg parasitoids
      of lepidopteran hosts (Trichogramma brassicae and T. evanescens) toward plant
      volatiles induced by different insect herbivores in olfactometer bioassays. We
      used a system consisting of a native crucifer, Brassica nigra, two naturally
      associated herbivores [the butterfly Pieris brassicae (eggs and caterpillars) and
      the aphid Brevicoryne brassicae] and an alien invasive herbivore (eggs and
      caterpillars of the moth Spodoptera exigua). We found that Trichogramma wasps
      were attracted by volatiles induced in the plants by P. brassicae eggs, but not
      by those induced in the plants by S. exigua eggs, indicating the specificity of
      the plant responses toward lepidopteran herbivores. The results of the chemical
      analysis revealed significant differences between the volatile blends emitted by
      plants in response to attack by P. brassicae and S. exigua eggs which were in
      agreement with the behavioural observations. We investigated the attraction of
      Trichogramma wasps toward P. brassicae egg-induced volatiles in plants
      simultaneously attacked by larvae and nymphs of different non-hosts. The two
      chewing caterpillars P. brassicae and S. exigua, but not the phloem-feeding aphid
      B. brassicae, can disrupt the attraction of Trichogramma species toward P.
      brassicae egg-induced volatiles. Indirect plant defenses are discussed in the
      context of multiple herbivory by evaluating the importance of origin, dietary
      specialization and feeding guild of different attackers on the recruitment of egg
      killing parasitoids. 

PMID- 25953115
TI  - When to initiate torpor use? Food availability times the transition to winter
      phenotype in a tropical heterotherm.
AB  - Timing of winter phenotype expression determines individual chances of survival
      until the next reproductive season. Environmental cues triggering this seasonal
      phenotypic transition have rarely been investigated, although they play a central
      role in the compensation of climatic fluctuations via plastic phenotypic
      adjustments. Initiation of winter daily torpor use-a widespread energy-saving
      phenotype-could be primarily timed according to anticipatory seasonal cues
      (anticipatory cues hypothesis), or flexibly fine-tuned according to actual energy
      availability (food shortage hypothesis). We conducted a food supplementation
      experiment on wild heterothermic primates (grey mouse lemurs, Microcebus murinus)
      at the transition to the food-limited dry season, i.e. the austral winter. As
      expected under the food shortage hypothesis, food-supplemented individuals
      postponed the seasonal transition to normal torpor use by 1-2 month(s), spent
      four times less torpid, and exhibited minimal skin temperature 6  degrees C
      higher than control animals. This study provides the first in situ experimental
      evidence that food availability, rather than abiotic cues, times the launching of
      torpor use. Fine-tuning of the timing of seasonal phenotypic transitions
      according to actual food shortage should provide heterotherms with a flexible
      adaptive mechanism to survive unexpected environmental fluctuations.

PMID- 25953116
TI  - Measurements of spatial population synchrony: influence of time series
      transformations.
AB  - Two mechanisms have been proposed to explain spatial population synchrony:
      dispersal among populations, and the spatial correlation of density-independent
      factors (the "Moran effect"). To identify which of these two mechanisms is
      driving spatial population synchrony, time series transformations (TSTs) of
      abundance data have been used to remove the signature of one mechanism, and
      highlight the effect of the other. However, several issues with TSTs remain, and
      to date no consensus has emerged about how population time series should be
      handled in synchrony studies. Here, by using 3131 time series involving 34 fish
      species found in French rivers, we computed several metrics commonly used in
      synchrony studies to determine whether a large-scale climatic factor
      (temperature) influenced fish population dynamics at the regional scale, and to
      test the effect of three commonly used TSTs (detrending, prewhitening and a
      combination of both) on these metrics. We also tested whether the influence of
      TSTs on time series and population synchrony levels was related to the features
      of the time series using both empirical and simulated time series. For several
      species, and regardless of the TST used, we evidenced a Moran effect on
      freshwater fish populations. However, these results were globally biased downward
      by TSTs which reduced our ability to detect significant signals. Depending on the
      species and the features of the time series, we found that TSTs could lead to
      contradictory results, regardless of the metric considered. Finally, we suggest
      guidelines on how population time series should be processed in synchrony
      studies. 

PMID- 25953117
TI  - Individual variation of isotopic niches in grazing and browsing desert ungulates.
AB  - Ungulates often adjust their diet when food availability varies over time.
      However, it is poorly understood when and to what extent individuals change their
      diet and, if they do so, if all individuals of a population occupy distinct or
      similar dietary niches. In the arid Namibian Kunene Region, we studied temporal
      variations of individual niches in grazing gemsbok (Oryx gazella gazella) and
      predominantly browsing springbok (Antidorcas marsupialis). We used variation in
      stable C and N isotope ratios of tail hair increments as proxies to estimate
      individual isotopic dietary niches and their temporal plasticity. Isotopic
      dietary niches of populations of the two species were mutually exclusive, but
      similar in breadth. Isotopic niche breadth of gemsbok was better explained by
      within-individual variation than by between-individual variation of stable
      isotope ratios, indicating that gemsbok individuals were facultative specialists
      in using isotopically distinct local food resources. In contrast, inter- and
      intra-individual variations contributed similarly to the isotopic niche breadth
      of the springbok population, suggesting a higher degree of individual isotopic
      segregation in a more generalist ungulate. In both species, between-individual
      variation was neither explained by changes in plant primary productivity, sex,
      geographical position nor by group size. Within species, individual dietary
      niches overlapped partially, suggesting that both populations included
      individuals with distinct isotopic dietary niches. Our study provides the first
      evidence for isotopic dietary niche segregation in individuals of two distinct
      desert ungulates. Similar, yet isotopically distinct dietary niches of
      individuals may facilitate partitioning of food resources and thus individual
      survival in desert ecosystems. 

PMID- 25953119
TI  - Team-based learning for midwifery education.
AB  - INTRODUCTION: Many US health care and education stakeholder groups, recognizing
      the need to prepare learners for collaborative practice in complex care
      environments, have called for innovative approaches in health care education.
      Team-based learning is an educational method that relies on in-depth student
      preparation prior to class, individual and team knowledge assessment, and use of
      small-group learning to apply knowledge to complex scenarios. Although team-based
      learning has been studied as an approach to health care education, its
      application to midwifery education is not well described. METHODS: A master's
      level, nurse-midwifery, didactic antepartum course was revised to a team-based
      learning format. Student grades, course evaluations, and aggregate American
      Midwifery Certification Board examination pass rates for 3 student cohorts
      participating in the team-based course were compared with 3 student cohorts
      receiving traditional, lecture-based instruction. RESULTS: Students had mixed
      responses to the team-based learning format. Student evaluations improved when
      faculty added recorded lectures as part of student preclass preparation.
      Statistical comparisons were limited by variations across cohorts; however,
      student grades and certification examination pass rates did not change
      substantially after the course revision. Although initial course revision was
      time-consuming for faculty, subsequent iterations of the course required less
      effort. DISCUSSION: Team-based learning provides students with more opportunity
      to interact during on-site classes and may spur application of knowledge into
      practice. However, it is difficult to assess the effect of the team-based
      learning approach with current measures. Further research is needed to determine
      the effects of team-based learning on communication and collaboration skills, as
      well as long-term performance in clinical practice. This article is part of a
      special series of articles that address midwifery innovations in clinical
      practice, education, interprofessional collaboration, health policy, and global
      health.

PMID- 25953120
TI  - Theoretical and Experimental Studies of Epidermal Heat Flux Sensors for
      Measurements of Core Body Temperature.
AB  - Long-term, continuous measurement of core body temperature is of high interest,
      due to the widespread use of this parameter as a key biomedical signal for
      clinical judgment and patient management. Traditional approaches rely on devices
      or instruments in rigid and planar forms, not readily amenable to intimate or
      conformable integration with soft, curvilinear, time-dynamic, surfaces of the
      skin. Here, materials and mechanics designs for differential temperature sensors
      are presented which can attach softly and reversibly onto the skin surface, and
      also sustain high levels of deformation (e.g., bending, twisting, and
      stretching). A theoretical approach, together with a modeling algorithm, yields
      core body temperature from multiple differential measurements from temperature
      sensors separated by different effective distances from the skin. The
      sensitivity, accuracy, and response time are analyzed by finite element analyses
      (FEA) to provide guidelines for relationships between sensor design and
      performance. Four sets of experiments on multiple devices with different
      dimensions and under different convection conditions illustrate the key features
      of the technology and the analysis approach. Finally, results indicate that
      thermally insulating materials with cellular structures offer advantages in
      reducing the response time and increasing the accuracy, while improving the
      mechanics and breathability. 

PMID- 25953121
TI  - Open Versus Arthroscopic Mosaicplasty of the Knee: A Cadaveric Assessment of
      Accuracy of Graft Placement Using Navigation.
AB  - PURPOSE: The purpose of this study was to compare an open freehand mosaicplasty
      technique with an arthroscopic technique for the treatment of osteochondral
      lesions by measuring the instrument deviation, quantifying this deviation, and
      providing numerical information on the difference in the outcomes of these
      techniques. METHODS: Four cadaveric knees were used. Reference markers were
      attached to the femur, tibia, and donor/recipient site guides. A total of 10
      osteochondral grafts were harvested and inserted into recipient sites
      arthroscopically and 10 similar grafts were inserted freehand. The angles of
      graft removal and placement were calculated for each of the surgical groups
      compared. Ostensibly, a navigation system was used as an aid, to measure the
      graft placement parameters. RESULTS: Statistical analysis revealed that there was
      no statistically significant difference between the arthroscopic method and the
      freehand method regarding the angle of graft removal at the donor site (P =
      .162), recipient site plug removal angle (P = .731), and recipient site graft
      placement angle (P = .630). In the freehand group, the mean angle of graft
      removal at the donor site was 12 degrees , the mean angle of recipient site plug
      removal was 10.7 degrees , and the mean angle of recipient site plug placement
      was 10.6 degrees . Using the arthroscopic technique, the mean angle of graft
      removal at the donor site was 17.14 degrees , the mean angle of recipient site
      plug removal was 12.0 degrees , and the mean angle of recipient site graft
      placement was 10.14 degrees . CONCLUSIONS: Our study revealed there was no
      statistically significant difference regarding precision and accuracy during
      harvesting, recipient site preparation, and plug placement between the 2
      techniques. CLINICAL RELEVANCE: Controversy exists whether an open or
      arthroscopic osteoarticular transfer system (OATS) technique provides superior
      accuracy. According to our results, there is no statistically significant
      difference regarding better visualization, precision, and accuracy between the
      freehand and arthroscopic techniques. However, larger number of specimens are
      required for study.

PMID- 25953118
TI  - Intrapatient Evolutionary Dynamics of Human Immunodeficiency Virus Type 1 in
      Individuals Undergoing Alternative Treatment Strategies with Reverse
      Transcriptase Inhibitors.
AB  - Structured treatment interruption (STI) has been trialed as an alternative to
      lifelong antiretroviral therapy (ART). We retrospectively performed single genome
      sequencing of the HIV-1 pol region from three patients representing different
      scenarios. They were either failing on continuous therapy (CT-F), failing STI
      (STI-F), or suppressing on STI (STI-S). Over 460 genomes were generated from
      three to five different time points over a 2-year period. We found multiple
      linked-resistant mutations in both treatment failures. However, the CT-F patient
      showed a stepwise accumulation of diverse, linked mutations whereas the STI-F
      patient had lineage turnover between treatment periods with recirculation of wild
      type and resistant variants from reservoirs. The STI-F patient showed a 7-fold
      increase in the third codon position substitution rate relative to the first and
      second positions compared to a 2-fold increase for CT-F and increased purifying
      selection in the pol gene (62 vs. 22 sites, respectively). An understanding of
      intrapatient viral dynamics could guide the future direction of treatment
      interruption strategies.

PMID- 25953122
TI  - Correlates With History of Injury in Youth and Adolescent Pitchers.
AB  - PURPOSE: To determine the factors within pitcher demographic characteristics,
      pitching history, and pitch kinematics, including velocity, that correlate with a
      history of pitching-related injury. METHODS: Demographic and kinematic data were
      collected on healthy youth and adolescent pitchers aged 9 to 22 years in
      preseason training during a single preseason using dual orthogonal high-speed
      video analysis. Pitchers who threw sidearm and those who had transitioned to
      another position were excluded. Players were asked whether they had ever had a
      pitching-related shoulder or elbow injury. Multivariate logistic regression
      analysis was performed on those variables that correlated with a history of
      injury. RESULTS: Four hundred twenty pitchers were included, of whom 31% had a
      history of a pitching-related injury. Participant height (P = .009, R(2) =
      0.023), pitching for more than 1 team (P = .019, R(2) = 0.018), and pitch
      velocity (P = .006, R(2) = 0.194) served as independent correlates of injury
      status. A model constructed with these 3 variables could correctly predict 77% of
      injury histories. Within our cohort, the presence of a 10-inch increase in height
      was associated with an increase in a history of injury by 20% and a 10-mph
      increase in velocity was associated with an increase in the likelihood of a
      history of injury by 12%. Playing for more than 1 team increased the likelihood
      of a history of injury by 22%. CONCLUSIONS: Pitch velocity, pitcher height, and
      pitching for more than 1 team correlate with a history of shoulder and elbow
      injury. Current recommendations regarding breaking pitches may not prevent
      injury. Pitchers should be cautioned about pitching for more than 1 team. Taller
      pitchers and high-velocity pitchers may be at risk of injury.

PMID- 25953124
TI  - A probabilistic approach for pediatric epilepsy diagnosis using brain functional
      connectivity networks.
AB  - BACKGROUND: The lives of half a million children in the United States are
      severely affected due to the alterations in their functional and mental abilities
      which epilepsy causes. This study aims to introduce a novel decision support
      system for the diagnosis of pediatric epilepsy based on scalp EEG data in a
      clinical environment. METHODS: A new time varying approach for constructing
      functional connectivity networks (FCNs) of 18 subjects (7 subjects from pediatric
      control (PC) group and 11 subjects from pediatric epilepsy (PE) group) is
      implemented by moving a window with overlap to split the EEG signals into a total
      of 445 multi-channel EEG segments (91 for PC and 354 for PE) and finding the
      hypothetical functional connectivity strengths among EEG channels. FCNs are then
      mapped into the form of undirected graphs and subjected to extraction of graph
      theory based features. An unsupervised labeling technique based on Gaussian
      mixtures model (GMM) is then used to delineate the pediatric epilepsy group from
      the control group. RESULTS: The study results show the existence of a
      statistically significant difference (p < 0.0001) between the mean FCNs of PC and
      PE groups. The system was able to diagnose pediatric epilepsy subjects with the
      accuracy of 88.8% with 81.8% sensitivity and 100% specificity purely based on
      exploration of associations among brain cortical regions and without a priori
      knowledge of diagnosis. CONCLUSIONS: The current study created the potential of
      diagnosing epilepsy without need for long EEG recording session and time
      consuming visual inspection as conventionally employed.

PMID- 25953123
TI  - Changes of protein expression in prostate cancer having lost its androgen
      sensitivity.
AB  - OBJECTIVE: The majority of prostate cancers require androgen hormones for growth,
      and androgen ablation is an important part of the systemic treatment of advanced
      prostate cancer. Nevertheless, most of these cancers eventually relapse as they
      become less sensitive to androgen ablation and anti-androgen treatment.
      Elucidating the molecular events that are responsible for the conversion of
      androgen-sensitive cancers to androgen-refractory tumors may reveal new
      therapeutic opportunities. METHODS: In the present study, we investigated nine
      androgen-sensitive and nine androgen-refractory prostate cancer samples to
      evaluate the expression levels of 10 selected proteins that have been implicated
      in oncogenesis and cancer progression. RESULTS: Our immunohistochemical data show
      that three of the investigated proteins (i.e., minichromosome maintenance-2,
      methylguanine-DNA methyltransferase, and androgen receptor) are expressed at
      significantly different levels in the androgen-refractory cancer samples than in
      the androgen-sensitive tumors, whereas the expression levels of the seven other
      studied proteins (i.e., beta-catenin, p27, p21, p16, Ki67, hypoxia-inducible
      factor 1 alpha, and geminin) are not significantly different regarding the two
      groups. CONCLUSIONS: Our data suggest that the increased expression of
      minichromosome maintenance-2 and decreased expression of methylguanine-DNA
      methyltransferase related to androgen receptor are indicative of the androgen
      refractory stage in prostate cancer. Further studies are required to determine
      whether these expression changes play a causative role in the transition of
      androgen-sensitive to androgen-refractory prostate cancer.

PMID- 25953125
TI  - Body mass index and cognitive function: the potential for reverse causation.
AB  - OBJECTIVE: Higher late life body mass index (BMI) is unrelated to or even
      predicts lower risk of dementia in late life, a phenomenon that may be explained
      by reverse causation due to weight loss during preclinical phases of dementia. We
      aim to investigate the association of baseline BMI and changes in BMI with
      dementia in a large prospective cohort, and to examine whether weight loss
      predicts cognitive function. METHODS: Using a national cohort of adults average
      age 58 years at baseline in 1994 (n=7029), we investigated the associations
      between baseline BMI in 1994 and memory scores from 2000 to 2010. We also
      examined the association of BMI change from 1994 to 1998 with memory scores from
      2000 to 2010. Last, to investigate reverse causation, we examined whether memory
      scores in 1996 predicted BMI trajectories from 2000 to 2010. RESULTS: Baseline
      overweight predicted better memory scores 6 to 16 years later (beta=0.012, 95%
      confidence interval (CI)=0.001; 0.023). Decline in BMI predicted lower memory
      scores over the subsequent 12 years (beta=-0.026, 95% CI= -0.041; -0.011). Lower
      memory scores at mean age 60 years in 1996 predicted faster annual rate of BMI
      decline during follow-up (beta=-0.158 kg m(-2) per year, 95% CI= -0.223; -0.094).
      CONCLUSION: Consistent with reverse causation, greater decline in BMI over the
      first 4 years of the study was associated with lower memory scores over the next
      decade and lower memory scores was associated with a decline in BMI. These
      findings suggest that preclinical dementia predicts weight loss for people as
      early as their late 50s.

PMID- 25953126
TI  - Substrate binding properties of potato tuber ADP-glucose pyrophosphorylase as
      determined by isothermal titration calorimetry.
AB  - Substrate binding properties of the large (LS) and small (SS) subunits of potato
      tuber ADP-glucose pyrophosphorylase were investigated by using isothermal
      titration calorimetry. Our results clearly show that the wild type heterotetramer
      (S(WT)L(WT)) possesses two distinct types of ATP binding sites, whereas the
      homotetrameric LS and SS variant forms only exhibited properties of one of the
      two binding sites. The wild type enzyme also exhibited significantly increased
      affinity to this substrate compared to the homotetrameric enzyme forms. No stable
      binding was evident for the second substrate, glucose-1-phosphate, in the
      presence or absence of ATPgammaS suggesting that interaction of glucose-1
      phosphate is dependent on hydrolysis of ATP and supports the Theorell-Chance bi
      bi reaction mechanism. 

PMID- 25953127
TI  - Activity-based cost analysis of contrast-enhanced ultrasonography (CEUS) related
      to the diagnostic impact in focal liver lesion characterisation.
AB  - PURPOSE: This study was done to assess the clinical-diagnostic impact and cost of
      contrast-enhanced ultrasound (CEUS) versus computed tomography (CT) and magnetic
      resonance (MR) imaging in the characterisation of focal liver lesions. MATERIALS
      AND METHODS: CEUS with sulphur hexafluoride-filled microbubbles (SonoVue bolus
      2.4 ml) was performed in 157 patients with 160 focal liver lesions identified by
      other diagnostic techniques. CEUS images were obtained during the arterial (15 to
      35 s from contrast injection), portal venous (40 to 70 s) and late phase (up to
      300 s from microbubble injection). Contrast-enhanced CT was performed with a 64
      row multidetector CT. MRI was performed before and after administration of the
      liver-specific contrast agent gadobenate dimeglumine (Gd-BOPTA). A patient-by
      patient activity-based cost analysis was performed. RESULTS: CEUS led to a change
      in the diagnostic workup in 131/157 patients (83.4 %) and in the therapeutic
      workup in 93/157 patients (59.2 %). CEUS allowed for the final diagnosis to be
      established in 133/157 patients (84.7 %). The full cost of CEUS was lower than
      that of contrast-enhanced CT and MR imaging. CONCLUSIONS: CEUS determined a
      change in the diagnostic and therapeutic workup in the characterisation of focal
      liver lesions and reduced the full costs of the diagnostic process. MAIN
      MESSAGES: * CEUS allows a correct diagnosis in more than 80 % of focal liver
      lesions. * CEUS has a significant impact on the diagnosis of focal liver lesions.
      * CEUS examination of focal liver lesions reduces total costs. * Dynamic MR with
      hepato-specific contrast medium remains the reference standard for lesion
      characterisation. * CEUS is low-cost, versatile and accurate in the
      characterisation of focal liver lesions.

PMID- 25953128
TI  - Effect of a postoperative outpatient pulmonary rehabilitation program on physical
      activity in patients who underwent pulmonary resection for lung cancer.
AB  - AIM: Physical activity (PA) has been associated with an improvement in survival
      for individuals with cancer. However, little is known about the effect of
      postoperative pulmonary rehabilitation on PA after lobectomy in patients with
      lung cancer. The present study investigated the effect of outpatient
      rehabilitation on PA in patients with cancer after lung resection. METHODS: A
      total of 19 patients with lung cancer were recruited for this study and completed
      a preoperative rehabilitation program. One group of nine patients completed a
      postoperative outpatient pulmonary rehabilitation program (rehabilitation) and
      another group of 10 patients did not (control), but were similarly followed up.
      Preoperative lung function, assessed by forced expiratory volume in 1 s (FEV1 ),
      body mass index (BMI) and St. George's Respiratory Questionnaire (SGRQ) score
      were not different between groups. PA was measured before and 2 months after
      surgery using a three-axis accelerometer for 5-6 days. PA level (PAL) was defined
      as total energy expenditure divided by basal metabolic rate. RESULTS:
      Preoperative PAL was not different between groups. However, postoperative versus
      preoperative PAL was significantly lower in the control versus the rehabilitation
      group (P < 0.01), and PAL decline was less for the rehabilitation versus the
      control group (P < 0.001). A subgroup analysis showed improvement in
      postoperative PAL in rehabilitation patients aged <75 years and older.
      CONCLUSIONS: Two months after lung resection surgery, patients had not recovered
      to the preoperative PAL. However, compared with the control group, there was an
      improvement in the postoperative PAL in patients, including older patients, who
      underwent outpatient pulmonary rehabilitation. Geriatr Gerontol Int 2016; 16: 550
      555.

PMID- 25953129
TI  - Intensified shigellosis epidemic associated with sexual transmission in men who
      have sex with men--Shigella flexneri and S. sonnei in England, 2004 to end of
      February 2015.
AB  - Surveillance data suggest an intensification of the shigellosis epidemic
      associated with sexual transmissionin men who have sex with men (MSM) in England
      with separate introductions into the population. In 2014, sexual transmission
      between MSM might have accounted for 97%, 89%, and 43% of non-travel associated
      Shigella flexneri 3a and S. flexneri 2a, andS. sonnei diagnoses. Clinicians
      should sensitively ascertain sexual history for men with enteric infections to
      facilitate prompt diagnosis and appropriate management.

PMID- 25953130
TI  - Contribution of transmission in HIV-positive men who have sex with men to
      evolving epidemics of sexually transmitted infections in England: an analysis
      using multiple data sources, 2009-2013.
AB  - HIV seroadaptive behaviours may have contributed to greater sexually transmitted
      infection (STI) transmission in HIV-positive men who have sex with men(MSM) and
      to the global increase in STIs. Using multiple national surveillance data sources
      and population survey data, we estimated the risk of STIs in HIV-positive MSM and
      assessed whether transmission in HIV-positive MSM has contributed to recent STI
      epidemics in England. Since 2009, an increasing proportion of STIs has been
      diagnosed in HIV-positive MSM, and currently, the population rate of acute
      bacterial STIs is up to four times that of HIV-negative or undiagnosed MSM.
      Almost one in five of all diagnosed HIV-positive MSM in England had an acute STI
      diagnosed in 2013. From 2009 to 2013, the odds of being diagnosed with syphilis
      increased from 2.71 (95% confidence interval (CI) 2.41-3.05, p<0.001) to 4.05
      (95%CI 3.70-4.45, p<0.001) in HIV-positive relative to HIV negative/undiagnosed
      MSM. Similar trends were seen for gonorrhoea and chlamydia. Bacterial STI re
      infection rates were considerably higher in HIV-positive MSM over a five-year
      follow-up period, indicative of rapid transmission in more dense sexual
      networks.These findings strongly suggest that the sexual health of HIV-positive
      MSM in England is worsening, which merits augmented public health interventions
      and continued monitoring.

PMID- 25953131
TI  - Internet-based recruitment system for HIV and STI screening for men who have sex
      with men in Estonia, 2013: analysis of preliminary outcomes.
AB  - The aim of the current project was to develop an Internet-based recruitment
      system for HIV and sexually transmitted infection (STI) screening for men who
      have sex with men (MSM) in Estonia in order to collect biological samples during
      behavioural studies. In 2013, an Internet-based HIV risk-behaviour survey was
      conducted among MSM living in Estonia. After completing the questionnaire, all
      participants were offered anonymous and free-of-charge STI testing. They could
      either order a urine sample kit by post to screen for chlamydia infections
      (including lymphogranuloma venereum (LGV)), trichomoniasis, gonorrhoea and
      Mycoplasma genitalium infections, or visit a laboratory for HIV, hepatitis A
      virus, hepatitis B virus,hepatitis C virus and syphilis screening. Of 301
      participants who completed the questionnaire, 265 (88%),reported that they were
      MSM. Of these 265 MSM,68 (26%) underwent various types of testing. In the
      multiple regression analysis, Russian as the first language,previous HIV testing
      and living in a city or town increased the odds of testing during the study.
      Linking Internet-based behavioural data collection with biological sample
      collection is a promising approach. As there are no specific STI services for MSM
      in Estonia,this system could also be used as an additional option for anonymous
      and free-of-charge STI screening.

PMID- 25953133
TI  - A systematic review of evidence to inform HIV prevention interventions among men
      who have sex with men in Europe.
AB  - An estimated 42% of all newly diagnosed HIV cases in Europe in 2013 were
      transmitted during sex between men. This review was performed to identify and
      describe studies evaluating the efficacy and effectiveness of HIV prevention
      interventions among men who have sex with men (MSM), in relation to
      implementation data from European settings. A systematic search was performed
      individually for 24 interventions.Data were extracted from studies including
      efficacy or implementation data from European settings,appraised for efficacy,
      implementation and plausibility, and assigned a grade (1-4) according to the
      Highest Attainable Standard of Evidence (HASTE)framework. Four interventions
      (condom use, peer outreach,peer-led groups, and using universal coverage of
      antiretroviral treatment and treatment as prevention)were assigned the highest
      HASTE grade, 1. Another four interventions were assigned 2a for probable
      recommendation, including voluntary counseling and testing for HIV, using condom
      compatible lubricant,using post-exposure prophylaxis, and individual counselling
      for MSM living with HIV. In addition, seven interventions were assigned a grade
      of 2b, for possible recommendation. Encouragingly, 15 interventions were graded
      to be strongly, probably or possibly recommended.In the relatively resource-rich
      European setting, there is an opportunity to provide global leadership with
      regard to the regional scale-up of comprehensive HIV prevention interventions for
      MSM.

PMID- 25953132
TI  - Anal human papillomavirus and HIV: A cross-sectional study among men who have sex
      with men in Moscow, Russia, 2012-2013.
AB  - Anal human papillomavirus (HPV) is prevalent among men who have sex with men
      (MSM), but has not been studied in the Russian Federation. A cross-sectional
      survey and HPV genotyping were conducted among HIV seropositive (n=58) and
      seronegative MSM (n=65)in Moscow. Multivariable logistic regression was performed
      to identify correlates of infection with oncogenic HPV genotypes 16 and/or 18
      (HPV 16/18). Forty per cent (49/124) of all MSM were infected with at least one
      anal HPV genotype, 31.5% (39/124) had HPV16/18,and 11.5% (14/121) had high-grade
      squamous intraepithelial lesions (HSIL). HPV 16/18 was more prevalent in HIV
      seropositive than seronegative men (24/58,41.4% vs 15/65, 23.1%; p=0.03). HIV
      infection was independently associated with HPV 16/18 (adjusted odds ratio (AOR):
      5.08; 95% confidence intervals (CI):1.49-17.34, p=0.01), as was having 2-4 steady
      male sex partners in the last year (vs <= 1 partner; AOR: 6.99;95%CI: 1.94-25.24,
      p<0.01). History of prison/detention,migration to/within Russia and use of
      incompatible lubricants were marginally associated with HPV16/18 (p<0.10).
      Comprehensive prevention options are needed to address HIV and HPV infection
      among MSM in Russia and may benefit from inclusion of young men in piloted HPV
      vaccination programmes.

PMID- 25953136
TI  - Microextraction methods for the determination of phthalate esters in liquid
      samples: A review.
AB  - 1,2-Benzenedicarboxylic acid esters, commonly referred to as phthalate esters,
      form a group of compounds that are mainly used as plasticizers in polymers.
      Because phthalate esters are not chemically bound to the plastics, they can be
      released easily from products and migrate into the food or water that comes into
      direct contact. Due to their widespread use, they are considered as ubiquitous
      environmental pollutants. Phthalate esters are regarded as endocrine disrupting
      compounds by means of their carcinogenic effect. Phthalate esters can be analyzed
      by gas chromatography or high-performance liquid chromatography, however, their
      sensitivity and selectivity limit their direct use for determination of
      phthalates at very low level of concentrations exist in environmental samples
      with complex matrices. Therefore a sample pretreatment prior to their analysis is
      necessary. In this review, the historical development and overview of sample
      preparation methodologies have briefly been discussed and a comprehensive
      application of these methods in combination with different analytical techniques
      for preconcentration and determination of phthalate esters in various matrices
      have been summarized. Finally, a critical comparison of the different approaches
      in terms of enrichment factors achieved, extraction efficiency, precision,
      selectivity and simplicity of operation is provided. 

PMID- 25953135
TI  - Quantitative assessment of paravalvular regurgitation following transcatheter
      aortic valve replacement.
AB  - BACKGROUND: Paravalvular aortic regurgitation (PAR) following transcatheter
      aortic valve implantation (TAVI) is well acknowledged. Despite improvements,
      echocardiographic measurement of PAR largely remains qualitative. Cardiovascular
      magnetic resonance (CMR) directly quantifies AR with accuracy and
      reproducibility. We compared CMR and transthoracic echocardiography (TTE)
      analysis of pre-operative and post-operative aortic regurgitation in patients
      undergoing both TAVI and surgical aortic valve replacement (AVR). METHODS: Eighty
      seven patients with severe aortic stenosis undergoing TAVI (56 patients) or AVR
      were recruited. CMR (1.5 T) and transthoracic echocardiography (TTE) were carried
      out pre-operatively and a median of 6 days post-operatively. The CMR protocol
      included regurgitant aortic flows using through-plane phase-contrast velocity.
      None/trivial, mild, moderate and severe AR by CMR was defined as <=8%, 9-20%, 21
      39%, >40% regurgitant fractions respectively. RESULTS: Pre- and post-operative
      left ventricular ejection fraction (LVEF) was similar. Post-procedure aortic
      regurgitant fraction using CMR was higher in the TAVI group (TAVI 16 +/- 13% vs.
      AVR 4 +/- 4%, p < 0.01). Comparing CMR to TTE, 27 of 56 (48%) TAVI patients had
      PAR which was at least one grade more severe on CMR than TTE (Z = -4.56, p
      <0.001). Sensitivity analysis confirmed the difference in PAR grade between TTE
      and CMR in the TAVI group (Z = -4.49, p < 0.001). CONCLUSION: When compared to
      CMR based quantitative analysis, TTE underestimated the degree of paravalvular
      aortic regurgitation. This underestimation may in part explain the findings of
      increased mortality associated with mild or greater AR by TTE in the PARTNER
      trial. Paravalvular aortic regurgitation post TAVI assessed as mild by TTE may in
      fact be more severe.

PMID- 25953137
TI  - Disability and Discussions of Health-Related Behaviors Between Youth and Health
      Care Providers.
AB  - PURPOSE: The purpose of this study was to examine the likelihood of discussing
      health-related behaviors with health care providers (HCPs), comparing youth with
      and without mobility limitations (MLs). METHODS: Analyses were conducted using
      baseline data from the MyPath study. Adolescents and young adults between the
      ages of 16 and 24 years completed a survey about their health care and health
      related experiences. Analyses assessed the relationship between mobility status
      and discussing health-related behaviors with an HCP. Secondary analyses examined
      the extent to which adolescents and young adults' engagement in these behaviors
      was associated with these discussions. RESULTS: Overall, we found low rates of
      discussions about the following topics: substance use, sexual and reproductive
      health, healthy eating, weight, and physical activity. Adolescents and young
      adults with MLs were less likely to report discussing substance use and sexual
      and reproductive health, but were more likely to discuss healthy eating, weight,
      and physical activity than peers without MLs. Those adolescents and young adults
      who reported substance use had higher odds of discussing this topic and those who
      reported having sexual intercourse had higher odds of discussing sexual and
      reproductive health. CONCLUSIONS: Results suggest mobility status and a young
      person's engagement in health risk and promoting behaviors are associated with
      the likelihood of discussing these behaviors with an HCP. It is important that
      HCPs view adolescents and young adults with MLs as needing the same counseling
      and guidance about health-related behaviors as any young person presenting
      him/herself for treatment.

PMID- 25953138
TI  - Comparative Analysis of Root Dentin Morphology and Structure of Human Versus
      Bovine Primary Teeth.
AB  - This study evaluated the structural and morphological differences between human
      and bovine primary root canals. Primary human maxillary central incisors (H)
      (n=9) and primary bovine incisors (B) (n=9) were selected. The roots were
      sectioned in the vestibular-lingual direction, planed and delimited in cervical,
      middle, and apical thirds. Tubule density (number of tubules per mm2) and
      diameter were analyzed by scanning electron microscopy (1,000 and 5,000*) using
      Image J 1.47 software. Data were submitted to two-way repeated measures ANOVA and
      Tukey tests (alpha=0.05). The highest tubule density was observed for B (28.527+/
      1.717 mm2) compared with H (15.931+/-0.170 mm2) (p<0.01). Regarding root thirds,
      the cervical third presented a greater tubule density (26.417+/-11.654 mm2) than
      the apical third (17.999+/-5.873 mm2). The diameter of the dentin tubules was not
      different for cervical (3.50+/-0.08 um), middle (3.45+/-0.30 um) and apical
      thirds (3.42+/-0.33 um) and substrate (H-3.29+/-0.14 um; B-3.63+/-0.06 um). It
      could be concluded that: (1) the radicular dentin structure of human and bovine
      primary teeth and root thirds differ in terms of the tubule density; (2) the
      radicular dentin morphology of human and bovine primary teeth and root thirds are
      similar in terms of the diameter of the dentin tubules. 

PMID- 25953139
TI  - Direct-acting antiviral drug approvals for treatment of chronic hepatitis C virus
      infection: Scientific and regulatory approaches to clinical trial designs.
AB  - Therapeutic options for treatment of chronic hepatitis C have improved
      substantially since the approval of direct-acting antiviral agents (DAAs).
      Several interferon (IFN)-free or IFN- and ribavirin (RBV)-free treatment regimens
      with shorter durations and improved efficacy and safety profiles are now
      available. The U.S. Food and Drug Administration (FDA) used several scientific
      approaches and regulatory mechanisms, such as (1) use of a "validated" surrogate
      (sustained virological response) for a primary endpoint, (2) shortening the time
      point for measuring the surrogate by 12 weeks, (3) use of historical controls
      when clinically appropriate, and (4) use of modeling when scientifically sound to
      extend treatment indications to subpopulations not fully evaluated in clinical
      trials, which had an impact on DAA development and subsequent approvals. This
      article intends to provide increased transparency about the FDA's scientific
      approaches and regulatory processes that supported drug development and marketing
      approval of DAAs for treatment of hepatitis C, a serious, life-threatening
      infection.

PMID- 25953140
TI  - The cascade synthesis of quinazolinones and quinazolines using an alpha-MnO2
      catalyst and tert-butyl hydroperoxide (TBHP) as an oxidant.
AB  - Heterogeneously catalyzed synthesis of quinazolinones or quinazolines is reported
      in this study. An alpha-MnO2 catalyst is found to be highly active and selective
      in the oxidative cyclization of anthranilamides or aminobenzylamines with
      alcohols using TBHP as an oxidant. This protocol exhibits a broad substrate
      scope, and is operationally simple without an additive. 

PMID- 25953141
TI  - Non-invasive measurement of adrenergic baroreflex during Valsalva maneuver
      reveals three distinct patterns in healthy subjects.
AB  - OBJECTIVE: To investigate hemodynamic trans-phasic fluctuations in Valsalva
      maneuver (VM) and relate them to adrenergic baroreflex sensitivity (BRSa)
      indices. METHODS: In a healthy population (n=107) with a young age predominance
      (32 +/- 15 years) systolic blood pressure (SBP) and BRSa indices in VM were
      studied. RESULTS: Augmented and Suppressed Autonomic Responses (AAR, 28%; SAR,
      15%, respectively), in addition to Balanced Autonomic Response (BAR, 40%), were
      found. There was a predominance for an unbalanced SBP response (67% in AAR, 69%
      in SAR, vs. 53% in BAR) in subjects ages 20-29. Compared to BAR and AAR, SAR had
      insignificant female predominance (51% and 47% vs. 75% respectively, p>0.05). AAR
      had the highest alternative BRSa (BRSa1) compared to SAR and BAR (26.73 +/- 17.97
      mmHg/s vs. 8.64 +/- 5.33 mmHg/s and 15.68 +/- 10.40 mmHg/s respectively, p<0.01).
      CONCLUSIONS: Qualitative evaluation revealed three distinct patterns in response
      to VM. Late phase II was found to be a key factor in VM patterns and as such,
      argues to include late phase II parameters such as hemodynamic and time indices
      in BRSa evaluation. SIGNIFICANCE: These findings may be of use in future
      evaluations when identifying mild autonomic dysfunction and/or distinguishing
      typical and atypical SBP patterns in a healthy population.

PMID- 25953142
TI  - Low- and high-frequency subcortical SEP amplitude reduction during pure passive
      movement.
AB  - OBJECTIVES: To investigate the effect of pure passive movement on both cortical
      and subcortical somatosensory evoked potentials (SEPs). METHODS: Median nerve
      SEPs were recorded in 8 patients suffering from Parkinson's disease (PD) and two
      patients with essential tremor. PD patients underwent electrode implantation in
      the subthalamic (STN) nucleus (3 patients) and pedunculopontine (PPTg) nucleus (5
      patients), while 2 patients with essential tremor were implanted in the ventral
      intermediate nucleus (VIM) of the thalamus. In anesthetized patients, SEPs were
      recorded at rest and during a passive movement of the thumb of the stimulated
      wrist from the intracranial electrode contacts and from the scalp. Also the high
      frequency oscillations (HFOs) were analyzed. RESULTS: Amplitudes of both deep and
      scalp components were decreased during passive movement, but the reduction was
      higher at cortical than subcortical level. Also the HFOs were reduced by
      movement. CONCLUSION: The different amount of the movement-related decrease
      suggests that the cortical SEP gating is not only the result of a subcortical
      somatosensory volley attenuation, but a further mechanism acting at cortical
      level should be considered. SIGNIFICANCE: Our results are important for
      understanding the physiological mechanism of the sensory-motor interaction during
      passive movement.

PMID- 25953143
TI  - Use of Orbital Conformer to Improve Speech in Patients with Confluent
      Maxillectomy and Orbital Defects.
AB  - The basic objective in prosthetic restoration of confluent maxillary and orbital
      defects is to achieve a comfortable, cosmetically acceptable prosthesis that
      restores speech, deglutition, and mastication. It is a challenging task
      complicated by the size and shape of the defects. The maxillary obturator
      prosthesis often satisfies the objective of adequate deglutition; however,
      orbital defects that are not obturated in the medial, septal, or posterior walls
      allow air to escape, negatively impacting phonation. This article describes a
      technique to achieve favorable prosthetic rehabilitation in a patient with a
      maxillectomy and ipsilateral orbital exenteration. The prosthetic components
      include maxillary obturator, orbital conformer, and orbital prosthesis connected
      using rigid magnetic attachments. 

PMID- 25953145
TI  - Evaluation of a new rapid test for carbapenemase detection in carbapenem
      resistant Enterobacteriaceae.
AB  - We evaluated a new phenotypic test for carbapenemase detection. A total of 100
      Enterobacteriaceae isolates were selected. The test was compared with
      conventional PCR for bla(KPC) and bla(NDM) detection. We found 100% sensitivity
      and specificity, suggesting that this test may be a feasible alternative for
      rapid carbapenemase detection.

PMID- 25953144
TI  - Feasibility of a multimodal (18)F-FDG-directed lymph node surgical excisional
      biopsy approach for appropriate diagnostic tissue sampling in patients with
      suspected lymphoma.
AB  - BACKGROUND: F-FDG PET/CT imaging is widely utilized in the clinical evaluation of
      patients with suspected or documented lymphoma. The aim was to describe our
      cumulative experience with a multimodal (18)F-FDG-directed lymph node surgical
      excisional biopsy approach in patients with suspected lymphoma. METHODS: Thirteen
      patients (mean age 51 (+/- 16;22-76) years), with suspected new or suspected
      recurrent lymphoma suggested by (18)F-FDG-avid lesions seen on prior diagnostic
      whole-body PET/CT imaging, were injected IV with (18)F-FDG prior to undergoing
      same-day diagnostic lymph node surgical excisional biopsy in the operating room.
      Various (18)F-FDG detection strategies were used on the day of surgery,
      including, (1) same-day pre-resection patient PET/CT; (2) intraoperative gamma
      probe assessment; (3) clinical scanner specimen PET/CT imaging of whole
      surgically excised tissue specimens; (4) specimen gamma well counts; and/or (5)
      same-day post-resection patient PET/CT. RESULTS: Same-day (18)F-FDG injection
      dose was 14.8 (+/- 2.4;12.5-20.6) millicuries or 548 (+/- 89;463-762)
      megabecquerels. Sites of (18)F-FDG-avid lesions were 4 inguinal, 3 cervical, 3
      abdominal/retroperitoneal, 2 axillary, and 1 gluteal region subcutaneous tissue.
      Same-day pre-resection patient PET/CT was performed on 6 patients. Intraoperative
      gamma probe assessment was performed on 13 patients. Clinical scanner PET/CT
      imaging of whole surgically excised tissue specimens was performed in 10 cases.
      Specimen gamma well counts were performed in 6 cases. Same-day post-resection
      patient PET/CT imaging was performed on 8 patients. Time from (18)F-FDG injection
      to same-day pre-resection patient PET/CT, intraoperative gamma probe assessment,
      and same-day post-resection patient PET/CT were 76 (+/- 8;64-84), 240 (+/- 63;168
      304), and 487 (+/- 104;331-599) minutes, respectively. Time from (18)F-FDG
      injection to clinical scanner PET/CT of whole surgically excised tissue specimens
      was 363 (+/- 60;272-446) minutes. Time from (18)F-FDG injection to specimen gamma
      well counts was 591 (+/- 96;420-689) minutes. Intraoperative gamma probe
      assessment successfully identified (18)F-FDG-avid lesions in 12/13 patients.
      Histopathologic evaluation confirmed lymphoma in 12/13 patients and benign
      disease in 1/13 patients. CONCLUSIONS: A multimodal approach to (18)F-FDG
      directed lymph node surgical excisional biopsy for suspected lymphoma is
      technically feasible for guiding appropriate diagnostic tissue sampling of lymph
      nodes seen as (18)F-FDG-avid lesions on diagnostic (18)F-FDG PET/CT imaging.

PMID- 25953146
TI  - Genetic architecture of variation in heading date among Asian rice accessions.
AB  - BACKGROUND: Heading date, a crucial factor determining regional and seasonal
      adaptation in rice (Oryza sativa L.), has been a major selection target in
      breeding programs. Although considerable progress has been made in our
      understanding of the molecular regulation of heading date in rice during last two
      decades, the previously isolated genes and identified quantitative trait loci
      (QTLs) cannot fully explain the natural variation for heading date in diverse
      rice accessions. RESULTS: To genetically dissect naturally occurring variation in
      rice heading date, we collected QTLs in advanced-backcross populations derived
      from multiple crosses of the japonica rice accession Koshihikari (as a common
      parental line) with 11 diverse rice accessions (5 indica, 3 aus, and 3 japonica)
      that originate from various regions of Asia. QTL analyses of over 14,000
      backcrossed individuals revealed 255 QTLs distributed widely across the rice
      genome. Among the detected QTLs, 128 QTLs corresponded to genomic positions of
      heading date genes identified by previous studies, such as Hd1, Hd6, Hd3a, Ghd7,
      DTH8, and RFT1. The other 127 QTLs were detected in different chromosomal regions
      than heading date genes. CONCLUSIONS: Our results indicate that advanced
      backcross progeny allowed us to detect and confirm QTLs with relatively small
      additive effects, and the natural variation in rice heading date could result
      from combinations of large- and small-effect QTLs. We also found differences in
      the genetic architecture of heading date (flowering time) among maize,
      Arabidopsis, and rice.

PMID- 25953148
TI  - A Randomized Clinical Trial Comparison Between Pivotal Response Treatment (PRT)
      and Adult-Driven Applied Behavior Analysis (ABA) Intervention on Disruptive
      Behaviors in Public School Children with Autism.
AB  - Children with autism often demonstrate disruptive behaviors during demanding
      teaching tasks. Language intervention can be particularly difficult as it
      involves social and communicative areas, which are challenging for this
      population. The purpose of this study was to compare two intervention conditions,
      a naturalistic approach, Pivotal Response Treatment (PRT) with an adult-directed
      ABA approach on disruptive behavior during language intervention in the public
      schools. A randomized clinical trial design was used with two groups of children,
      matched according to age, sex and mean length of utterance. The data showed that
      the children demonstrated significantly lower levels of disruptive behavior
      during the PRT condition. The results are discussed with respect to antecedent
      manipulations that may be helpful in reducing disruptive behavior. 

PMID- 25953147
TI  - Low health literacy and evaluation of online health information: a systematic
      review of the literature.
AB  - BACKGROUND: Recent years have witnessed a dramatic increase in consumer online
      health information seeking. The quality of online health information, however,
      remains questionable. The issue of information evaluation has become a hot topic,
      leading to the development of guidelines and checklists to design high-quality
      online health information. However, little attention has been devoted to how
      consumers, in particular people with low health literacy, evaluate online health
      information. OBJECTIVE: The main aim of this study was to review existing
      evidence on the association between low health literacy and (1) people's ability
      to evaluate online health information, (2) perceived quality of online health
      information, (3) trust in online health information, and (4) use of evaluation
      criteria for online health information. METHODS: Five academic databases
      (MEDLINE, PsycINFO, Web of Science, CINAHL, and Communication and Mass-media
      Complete) were systematically searched. We included peer-reviewed publications
      investigating differences in the evaluation of online information between people
      with different health literacy levels. RESULTS: After abstract and full-text
      screening, 38 articles were included in the review. Only four studies
      investigated the specific role of low health literacy in the evaluation of online
      health information. The other studies examined the association between
      educational level or other skills-based proxies for health literacy, such as
      general literacy, and outcomes. Results indicate that low health literacy (and
      related skills) are negatively related to the ability to evaluate online health
      information and trust in online health information. Evidence on the association
      with perceived quality of online health information and use of evaluation
      criteria is inconclusive. CONCLUSIONS: The findings indicate that low health
      literacy (and related skills) play a role in the evaluation of online health
      information. This topic is therefore worth more scholarly attention. Based on the
      results of this review, future research in this field should (1) specifically
      focus on health literacy, (2) devote more attention to the identification of the
      different criteria people use to evaluate online health information, (3) develop
      shared definitions and measures for the most commonly used outcomes in the field
      of evaluation of online health information, and (4) assess the relationship
      between the different evaluative dimensions and the role played by health
      literacy in shaping their interplay.

PMID- 25953149
TI  - A review of the role of robotics in bariatric surgery.
AB  - The epidemic of obesity continues to be a major health issue. It is now almost
      uniform that surgical procedures for weight loss are performed with minimally
      invasive techniques. This article reviews the literature regarding obesity
      related health issues, in particular risk of malignancy, and the application of
      robotic technology in weight loss surgical procedures. With increasing literature
      and technology in surgical robotics, its application in the field of bariatric
      surgery continues to evolve.

PMID- 25953150
TI  - The HLA-B*4601-DRB1*0901 haplotype is positively correlated with juvenile ocular
      myasthenia gravis in a southern Chinese Han population.
AB  - Myasthenia gravis (MG) is a sporadic disorder that has been increasingly linked
      to inherited genetic factors. Previous studies have demonstrated that human
      leukocyte antigen (HLA) plays an important role in the pathogenesis of MG. We
      determined the genotypes of the HLA-A, B, and DRB1 alleles in 257 southern
      Chinese Han MG patients using polymerase chain reaction sequence-based typing
      (PCR-SBT). The allele frequencies in the MG patients were compared to 292 healthy
      controls using the case-control method. HLA-A*0207, HLA-B*4601, HLA-DRB1*0403,
      HLA-DRB1*0901, and HLA-DRB1*1602 were more frequent in juvenile ocular MG
      patients than controls. HLA-DRB1*0701 was significantly reduced in the juvenile
      ocular MG group compared with controls. HLA-A*0207-B*4601, HLA-B*4601-DRB1*0403,
      HLA-B*4601-DRB1*0901, and HLA-B*4601-DRB1*1602 were found to be in strong linkage
      disequilibrium in juvenile ocular MG patients. Within the MG patients, there was
      a strong positive association between HLA-B*4601-DRB1*0901 and juvenile ocular MG
      patients, and the value of odds ratios (OR) decreased as the disease became more
      severe and the age of onset increased. We believe this could be the main heredity
      phenotype in juvenile ocular MG patients from southern China and may be a
      clinical marker to predict the severity of the disease.

PMID- 25953152
TI  - Preparation of Pickering emulsions stabilized by metal organic frameworks using
      oscillatory woven metal micro-screen.
AB  - Uniform Pickering emulsions stabilized by metal organic frameworks (MOFs) MIL-101
      and ZIF-8 nanoparticles (NPs) were successfully prepared using an oscillatory
      woven metal microscreen (WMMS) emulsification system in the presence and the
      absence of surfactants. The effects of operating and system parameters including
      the frequency and amplitude of oscillation, the type of nano-particle and/or
      surfactant on the droplet size and coefficient of variance of the prepared
      emulsions are investigated. The results showed that both the hydrodynamics of the
      system and the hydrophobic/hydrophilic nature of the NP influenced the
      interfacial properties of the oil-water interface during droplet formation and
      after detachment, which in turn affected the final droplet size and distribution.
      Comparison between the measured and predicted droplet size using a simple torque
      balance (TB) model is discussed. 

PMID- 25953151
TI  - A normative study of the Italian printed word version of the free and cued
      selective reminding test.
AB  - According to the new research criteria for the diagnosis of Alzheimer's disease,
      episodic memory impairment, not significantly improved by cueing, is the core
      neuropsychological marker, even at a pre-dementia stage. The FCSRT assesses
      verbal learning and memory using semantic cues and is widely used in Europe.
      Standardization values for the Italian population are available for the colored
      picture version, but not for the 16-item printed word version. In this study, we
      present age- and education-adjusted normative data for FCSRT-16 obtained using
      linear regression techniques and generalized linear model, and critical values
      for classifying sub-test performance into equivalent scores. Six scores were
      derived from the performance of 194 normal subjects (MMSE score, range 27-30,
      mean 29.5 +/- 0.5) divided per decade (from 20 to 90), per gender and per level
      of education (4 levels: 3-5, 6-8, 9-13, >13 years): immediate free recall (IFR),
      immediate total recall (ITR), recognition phase (RP), delayed free recall (DFR),
      delayed total recall (DTR), Index of Sensitivity of Cueing (ISC), number of
      intrusions. This study confirms the effect of age and education, but not of
      gender on immediate and delayed free and cued recall. The Italian version of the
      FCSRT-16 can be useful for both clinical and research purposes.

PMID- 25953153
TI  - The BMJ requires data sharing on request for all trials.

PMID- 25953154
TI  - Lysine-Based Site-Directed Mutagenesis Increased Rigid beta-Sheet Structure and
      Thermostability of Mesophilic 1,3-1,4-beta-Glucanase.
AB  - 1,3-1,4-beta-Glucanase is widely applied in the food industry, while its low
      thermostability often reduces its performance. In a previous study, chemical
      modification of surface lysine residues was proved to increase the
      thermostability of beta-glucanase. To improve the thermostability, the mesophilic
      beta-glucanase from Bacillus terquilensis was rationally engineered through site
      directed mutagenesis of the 12 lysines into serines. The results showed that the
      K20S, K117S, and K165S mutants could both enhance the specific activities and
      thermostability of beta-glucanase. The triple mutant (K20S/K117S/K165S) could
      increase the optimal temperature and T50 value by 15 and 14  degrees C,
      respectively. Five percent more structured residues were observed in the mutant,
      which formed new beta-sheet structures in the concave side. Molecular dynamics
      simulation analysis showed that the flexibility in the mutation regions was
      decreased, which resulted in the overall rigidity of the beta-glucanase.
      Therefore, the lysine-based site-directed mutagenesis is a simple and effective
      method for improving the thermostability of beta-glucanase. 

PMID- 25953155
TI  - Design and synthesis of close analogs of LCRF-0004, a potent and selective RON
      receptor tyrosine kinase inhibitor.
AB  - New carboxamide head group analogs of thieno[3,2-b]pyridine-based kinase
      inhibitor LCRF-0004 were designed and synthesized. Potent and selective
      inhibitors of RON enzyme versus c-Met RTK were obtained. 

PMID- 25953156
TI  - Design, synthesis, and biological evaluation of benzofuran- and 2,3
      dihydrobenzofuran-2-carboxylic acid N-(substituted)phenylamide derivatives as
      anticancer agents and inhibitors of NF-kappaB.
AB  - With the aim of developing novel scaffolds as anticancer agents and inhibitors of
      NF-kappaB activity, 60 novel benzofuran- and 2,3-dihydrobenzofuran-2-carboxylic
      acid N-(substituted)phenylamide derivatives (1a-s, 2a-k, 3a-s, and 4a-k) were
      designed and synthesized from the reference lead compound KL-1156, which is an
      inhibitor of NF-kappaB translocation to the nucleus in LPS-stimulated RAW 264.7
      macrophage cells. The novel benzofuran- and 2,3-dihydrobenzofuran-2-carboxamide
      derivatives exhibited potent cytotoxic activities (measured by the sulforhodamine
      B assay) at low micromolar concentrations against six human cancer cell lines:
      ACHN (renal), HCT15 (colon), MM231 (breast), NUGC-3 (gastric), NCI-H23 (lung),
      and PC-3 (prostate). In addition, these compounds also inhibited LPS-induced NF
      kappaB transcriptional activity. The +M effect and hydrophobic groups on the N
      phenyl ring potentiated the anticancer activity and NF-kappaB inhibitory
      activity, respectively. However, according to the results of structure-activity
      relationship studies, only benzofuran-2-carboxylic acid N-(4'-hydroxy)phenylamide
      (3m) was the lead scaffold with both an outstanding anticancer activity and NF
      kappaB inhibitory activity. This novel lead scaffold may be helpful for
      investigation of new anticancer agents that act through inactivation of NF
      kappaB. 

PMID- 25953157
TI  - Response to dual HER2 blockade in a patient with HER3-mutant metastatic breast
      cancer.
AB  - BACKGROUND: HER3 activating mutations have been shown in preclinical models to be
      oncogenic and ligand-independent, but to depend on kinase-active HER2. PATIENTS
      AND METHODS: Whole-exome sequencing of the primary HER2-negative breast cancer
      and its HER2-negative synchronous liver metastasis from a 46-year-old female
      revealed the presence of an activating and clonal HER3 G284R mutation. RESULTS:
      HER2 dual blockade with trastuzumab and lapatinib as third-line therapy led to
      complete metabolic response in 2 weeks and confirmed radiological partial
      response after 8 weeks. Following the resection of the liver metastasis, the
      patient remains disease-free 40 weeks after initiation of the HER2 dual blockade
      therapy. Immunohistochemical analysis demonstrated a substantial reduction of
      phospho-rpS6 and phospho-AKT in the post-therapy biopsy of the liver metastasis.
      DISCUSSION: This is the first-in-man evidence that anti-HER2 therapies are likely
      effective in breast cancers harboring HER3 activating mutations.

PMID- 25953158
TI  - Draft Genome Sequence of Paenibacillus polymyxa EBL06, a Plant Growth-Promoting
      Bacterium Isolated from Wheat Phyllosphere.
AB  - Paenibacillus polymyxa strain EBL06 is a plant growth-promoting bacterium with
      high antifungal activity. The estimated genome of this strain is 5.68 Mb in size
      and harbors 4,792 coding sequences (CDSs). 

PMID- 25953159
TI  - Draft Genome Sequence of Citrobacter rodentium DBS100 (ATCC 51459), a Primary
      Model of Enterohemorrhagic Escherichia coli Virulence.
AB  - Citrobacter rodentium is a Gram-negative bacterium which causes transmissible
      murine colonic hyperplasia and models the virulence of enterohemorrhagic
      Escherichia coli in vivo. Thus, C. rodentium is used to study human
      gastrointestinal disease. We present the draft genome sequence of C. rodentium
      strain ATCC 51459, also known as DBS100. 

PMID- 25953161
TI  - Draft Genome Sequence of Brucella abortus Virulent Strain 544.
AB  - Here, we present the draft genome sequence and annotation of Brucella abortus
      virulent strain 544. The genome of this strain is 3,289,405 bp long, with 57.2%
      G+C content. A total of 3,259 protein-coding genes and 60 RNA genes were
      predicted. 

PMID- 25953160
TI  - Complete Closed Genome Sequences of a Mannheimia haemolytica Serotype A1
      Leukotoxin Deletion Mutant and Its Wild-Type Parent Strain.
AB  - Mannheimia haemolytica is a bacterial pathogen that secretes leukotoxin (LktA)
      which binds to leukocyte membranes via CD18, causing bacterial pneumonia in
      ruminants. We report the complete closed genome sequences of a leukotoxin mutant
      and its parent strain that are frequently used in respiratory disease studies. 

PMID- 25953162
TI  - Genome Sequence of Rhodococcus sp. Strain PML026, a Trehalolipid Biosurfactant
      Producer and Biodegrader of Oil and Alkanes.
AB  - Rhodococcus sp. strain PML026 produces an array of trehalolipid biosurfactant
      compounds in order to utilize hydrophobic carbon sources, such as oils and
      alkanes. Here, we report the high-quality draft genome sequence of this strain,
      which has a total length of 5,168,404 bp containing 4,835 protein-coding
      sequences, 12 rRNAs, and 45 tRNAs. 

PMID- 25953163
TI  - Complete Genome Sequence of Biocontrol Strain Pseudomonas fluorescens LBUM223.
AB  - Pseudomonas fluorescens LBUM223 is a plant growth-promoting rhizobacterium (PGPR)
      with biocontrol activity against various plant pathogens. It produces the
      antimicrobial metabolite phenazine-1-carboxylic acid, which is involved in the
      biocontrol of Streptomyces scabies, the causal agent of common scab of potato.
      Here, we report the complete genome sequence of P. fluorescens LBUM223. 

PMID- 25953164
TI  - First Draft Genome Sequence of a Human Coxiella burnetii Isolate, Originating
      from the Largest Q Fever Outbreak Ever Reported, the Netherlands, 2007 to 2010.
AB  - In 2009, Coxiella burnetii caused a large regional outbreak of Q fever in South
      Limburg, the Netherlands. Here, we announce the genome draft sequence of a human
      C. burnetii isolate, strain NL-Limburg, originating from this outbreak, including
      a brief summary of the genome's general features. 

PMID- 25953165
TI  - Complete Genome Sequence of an Enterotoxigenic Bacteroides fragilis Clinical
      Isolate.
AB  - Here we present the complete genome sequence of Bacteroides fragilis isolate
      BOB25. It is an enterotoxigenic isolate that was obtained from a stool sample of
      a patient with dysbiosis. 

PMID- 25953166
TI  - First complete genome sequence of an emerging cucumber green mottle mosaic virus
      isolate in north america.
AB  - The complete genome sequence (6,423 nucleotides [nt]) of an emerging cucumber
      green mottle mosaic virus (CGMMV) isolate on cucumber in North America was
      determined through deep sequencing of small (sRNA) and rapid amplification of
      cDNA ends. The virus shares 99% nucleotide sequence identity with the Asian
      genotype but only 90% with the European genotype. 

PMID- 25953167
TI  - Complete Genome Sequences of Two Strains of "Candidatus Filomicrobium marinum," a
      Methanesulfonate-Degrading Species.
AB  - Two novel methanesulfonate-degrading bacterial strains of "Candidatus
      Filomicrobium marinum" (strains Y and W) were isolated from a marine water
      enrichment, and their complete genome sequences are presented here. These are the
      first full genomes reported for the genus Filomicrobium and for methanesulfonate
      (MSA)-degrading bacteria. 

PMID- 25953168
TI  - Genome Sequence of Salmonella enterica Phage Det7.
AB  - Det7 is a Myoviridae bacteriophage that gains entry into its Salmonella enterica
      serovar Typhimurium host cells by adsorbing to O-antigen polysaccharide. We
      report here the complete 157,498-bp sequence of its genome. Det7, together with
      its Vi01-like relatives, are distantly related to phage T4. 

PMID- 25953169
TI  - Draft Genome Sequence of a Strain of Cosmopolitan Fungus Trichoderma atroviride.
AB  - An unknown fungus has been isolated as a contaminant of in vitro-grown fungal
      cultures. In an attempt to identify the contamination, we isolated the causal
      agent and performed whole-genome sequencing. BLAST analysis of the internal
      transcribed spacer (ITS) sequence against the NCBI database showed 100% identity
      to Trichoderma atroviride, and further alignment of the genome assembly confirmed
      the unknown fungus to be T. atroviride. Here, we report the draft genome sequence
      of a T. atroviride strain. 

PMID- 25953170
TI  - Complete genome sequences of chikungunya virus strains isolated in Mexico: first
      detection of imported and autochthonous cases.
AB  - The mosquito-borne chikungunya virus, an alphavirus of the Togaviridae family, is
      responsible for acute polyarthralgia epidemics. Here, we report the complete
      genome sequences of two chikungunya virus strains, InDRE04 and InDRE51,
      identified in the Mexican states of Jalisco and Chiapas in 2014. Phylogenetic
      analysis showed that both strains belong to the Asian genotype. 

PMID- 25953171
TI  - Draft Genome Sequence of the Polyhydroxyalkanoate-Producing Bacterium
      Burkholderia sacchari LMG 19450 Isolated from Brazilian Sugarcane Plantation
      Soil.
AB  - Burkholderia sacchari LMG 19450, isolated from the soil of a sugarcane plantation
      in Brazil, accumulates large amounts of polyhydroxyalkanoates from sucrose,
      xylose, other carbohydrates, and organic acids. We present the draft genome
      sequence of this industrially relevant bacterium, which is 7.2 Mb in size and has
      a G+C content of 64%. 

PMID- 25953172
TI  - Draft Genome Sequence of Pseudomonas sp. Strain 10-1B, a Polycyclic Aromatic
      Hydrocarbon Degrader in Contaminated Soil.
AB  - Pseudomonas sp. strain 10-1B was isolated from artificially polluted soil after
      selective enrichment. Its draft genome consists of several predicted genes that
      are involved in the hydroxylation of the aromatic ring, which is the rate
      limiting step in the biodegradation of polycyclic aromatic hydrocarbons. 

PMID- 25953173
TI  - Extreme Sensory Complexity Encoded in the 10-Megabase Draft Genome Sequence of
      the Chromatically Acclimating Cyanobacterium Tolypothrix sp. PCC 7601.
AB  - Tolypothrix sp. PCC 7601 is a freshwater filamentous cyanobacterium with complex
      responses to environmental conditions. Here, we present its 9.96-Mbp draft genome
      sequence, containing 10,065 putative protein-coding sequences, including 305
      predicted two-component system proteins and 27 putative phytochrome-class
      photoreceptors, the most such proteins in any sequenced genome. 

PMID- 25953174
TI  - Complete Genome Sequence of Cyanobacterium Geminocystis sp. Strain NIES-3708,
      Which Performs Type II Complementary Chromatic Acclimation.
AB  - To explore the variation of the light-regulated genes during complementary
      chromatic acclimation (CCA), we determined the complete genome sequence of the
      cyanobacterium Geminocystis sp. strain NIES-3708. Within the light-regulated
      operon for CCA, we found genes for phycoerythrin but not phycocyanin, suggesting
      that this cyanobacterium modulates phycoerythrin composition only (type II CCA). 

PMID- 25953175
TI  - Complete Genome Sequence of Bacillus megaterium Podophage Palmer.
AB  - Bacillus megaterium has been widely used as a research tool for decades. Its use
      is on the rise as a recombinant protein production host and as a bioremediation
      bacterium. Bacteriophages against this bacterium may have biotechnological
      applications. Here, we describe the novel podophage Palmer, which infects B.
      megaterium. 

PMID- 25953176
TI  - Draft Genome Sequence of Arthrobacter chlorophenolicus Strain Mor30.16, Isolated
      from the Bean Rhizosphere.
AB  - Bacteria of the genus Arthrobacter are commonly found in the soil and plant
      rhizosphere. In this study we report the draft genome of Arthrobacter
      chlorophenolicus strain Mor30.16 that was isolated from rhizosphere of beans
      grown in Cuernavaca Morelos, Mexico. This strain promotes growth and ameliorates
      drought stress in bean plants. 

PMID- 25953177
TI  - Complete Genome Sequence of Martelella endophytica YC6887, Which Has Antifungal
      Activity Associated with a Halophyte.
AB  - Martelella endophytica YC6887, which produces antifungal compounds against fungal
      and oomycete pathogens, was isolated from the root of a halophyte, Rosa rugosa,
      collected at a tidal flat in South Korea. Its full-genome sequence shows that it
      is a circular DNA, without a plasmid, of about 4.8 Mb in size. 

PMID- 25953178
TI  - Draft Genome Sequence of Bordetella bronchiseptica KU1201, the First Isolation
      Source of Arylmalonate Decarboxylase.
AB  - The analysis of the 6.8-Mbp draft genome sequence of the phenylmalonate
      assimilating bacterium Bordetella bronchiseptica KU1201 identified 6,358 protein
      coding sequences. This will give us an insight into the catabolic variability of
      this strain for aromatic compounds, along with the roles of arylmalonate
      decarboxylases in nature. 

PMID- 25953179
TI  - Complete Genome Sequence of Mycoplasma meleagridis, a Possible Emerging Pathogen
      in Chickens.
AB  - Mycoplasma meleagridis strain B2096 8B was isolated from domestic chickens in
      South Africa. The 845,307-bp full genome was sequenced, assembled, and annotated.

PMID- 25953180
TI  - Complete genome sequence of a lineage I peste des petits ruminants virus isolated
      in 1969 in west Africa.
AB  - We report the complete genome sequence of a lineage I peste des petits ruminants
      virus (E32/1969) isolated in a Senegalese laboratory in 1969. This is the
      earliest peste des petits ruminants virus of any lineage sequenced to date and
      only the second lineage I virus available in public databases. 

PMID- 25953181
TI  - Genome Sequences of Pseudoalteromonas Strains ATCC BAA-314, ATCC 70018, and ATCC
      70019.
AB  - The assembly and annotation of the draft genome sequences for Pseudoalteromonas
      strains ATCC BAA314, ATCC 700518, and ATCC 700519 reveal candidates for promoting
      symbiosis between Pseudoalteromonas strains and eukaryotes. Groups of genes
      generally associated with virulence are present in all three strains, suggesting
      that these bacteria may be pathogenic under specific circumstances. 

PMID- 25953182
TI  - Draft Genome Sequence of a Phthalate Ester-Degrading Bacterium, Rhizobium sp. LMB
      1, Isolated from Cultured Soil.
AB  - Rhizobium sp. LMB-1, newly isolated from greenhouse soil, can effectively degrade
      phthalate. Here, we present a 5.2-Mb assembly of this Rhizobium sp. genome for
      the first time. It may provide abundant molecular information for the
      transformation of phthalates. 

PMID- 25953183
TI  - Complete Genome Sequence Analysis of Bacillus subtilis T30.
AB  - The complete genome sequence of Bacillus subtilis T30 was determined by SMRT
      sequencing. The entire genome contains 4,138 predicted genes. The genome carries
      one intact prophage sequence (37.4 kb) similar to Bacillus phage SPBc2 and one
      incomplete prophage genome of 39.9 kb similar to Bacillus phage phi105. 

PMID- 25953184
TI  - Complete Genome Sequence of Clavibacter michiganensis subsp. insidiosus R1-1
      Using PacBio Single-Molecule Real-Time Technology.
AB  - We report here the complete genome sequence of Clavibacter michiganensis subsp.
      insidiosus R1-1, isolated in Minnesota, USA. The R1-1 genome, generated by a de
      novo assembly of PacBio sequencing data, is the first complete genome sequence
      available for this subspecies. 

PMID- 25953185
TI  - Draft Genome Sequences of Three Escherichia coli Strains with Different In Vivo
      Pathogenicities in an Avian (Ascending) Infection Model of the Oviduct.
AB  - Here, we present three draft genome sequences of Escherichia coli strains that
      experimentally were proven to possess low (strain D2-2), intermediate
      (Chronic_salp), or high virulence (Cp6salp3) in an avian (ascending) infection
      model of the oviduct. 

PMID- 25953186
TI  - Full-genome sequence of pantropic canine coronavirus.
AB  - Pantropic canine coronavirus (CCoV) was first detected in young dogs in Italy in
      2005, but the complete genome sequence of this virus had not yet been determined.
      Here, we report the full-length genome sequence of the prototype strain CB/05,
      which showed that this virus is genetically similar to CCoV-IIa viruses. 

PMID- 25953187
TI  - Genome Sequence of Halomonas sp. Strain KO116, an Ionic Liquid-Tolerant Marine
      Bacterium Isolated from a Lignin-Enriched Seawater Microcosm.
AB  - Halomonas sp. strain KO116 was isolated from Nile Delta Mediterranean Sea surface
      water enriched with insoluble organosolv lignin. It was further screened for
      growth on alkali lignin minimal salts medium agar. The strain tolerates the ionic
      liquid 1-ethyl-3-methylimidazolium acetate. Its complete genome sequence is
      presented in this report. 

PMID- 25953188
TI  - Draft Genome Sequence of Mycobacterium tuberculosis Strain E186hv of Beijing B0/W
      Lineage with Reduced Virulence.
AB  - We report a draft genome sequence of Mycobacterium tuberculosis strain E186hv,
      belonging to the Beijing B0/W lineage and isolated from a patient from Kurgan,
      Russia. This clinical isolate showed a reduced virulence phenotype unusual for
      this lineage and resistance to isoniazid, rifampin, ethambutol, pyrazinamide, and
      ofloxacin. We analyzed single nucleotide polymorphisms (SNPs) associated with
      virulence. 

PMID- 25953189
TI  - Complete genome sequence of canine papillomavirus type 16.
AB  - Papillomaviruses are epitheliotropic, circular, double-stranded DNA viruses
      within the family Papillomaviridae that are associated with benign and malignant
      tumors in humans and animals. We report the complete genome sequence of canine
      papillomavirus type 16 identified within multiple pigmented cutaneous plaques and
      squamous cell carcinoma from an intact female Basenji dog. 

PMID- 25953190
TI  - Genome Sequence of a Carbapenem-Resistant Strain of Ralstonia mannitolilytica.
AB  - Ralstonia mannitolilytica, a Gram-negative aerobic bacterium, is an opportunistic
      human pathogen that is becoming more common in cases of nosocomial infections. We
      report for the first time the whole-genome sequence analysis of R.
      mannitolilytica strain MRY14-0246, which carries the intrinsic OXA-443/OXA-22
      like and OXA-444/OXA-60-like beta-lactamase genes and is resistant to meropenem. 

PMID- 25953191
TI  - Draft Genome Sequence of Se(IV)-Reducing Bacterium Pseudomonas migulae ES3-33.
AB  - Pseudomonas migulae ES3-33 is a Gram-negative strain that strongly reduces Se(IV)
      and was isolated from a selenium mining area in Enshi, southwest China. Here we
      present the draft genome of this strain containing potential genes involved in
      selenite reduction and a large number of genes encoding resistances to copper and
      antibiotics. 

PMID- 25953192
TI  - Insights on Quorum-Quenching Properties of Lysinibacillus fusiformis Strain RB21,
      a Malaysian Municipal Solid-Waste Landfill Soil Isolate, via Complete Genome
      Sequence Analysis.
AB  - Lysinibacillus fusiformis strain RB21 is a quorum-quenching bacterium that is
      able to degrade quorum-sensing signaling molecules. Here, we present the first
      complete genome sequence of L. fusiformis strain RB21. The finished genome is 4.8
      Mbp in size, and the quorum-quenching gene was identified. 

PMID- 25953193
TI  - Probiotic supplements and debridement of peri-implant mucositis: a randomized
      controlled trial.
AB  - OBJECTIVE: The aim of this double-blind randomized placebo-controlled trial was
      to evaluate the effects of probiotic supplements in adjunct to conventional
      management of peri-implant mucositis. MATERIALS AND METHODS: Forty-nine adult
      patients with peri-implant mucositis were consecutively recruited after informed
      consent. After initial mechanical debridement and oral hygiene instructions, the
      patients received a topical oil application (active or placebo) followed by twice
      daily intake of lozenges (active or placebo) for 3 months. The active products
      contained a mix of two strains of Lactobacillus reuteri. Patients were clinically
      monitored and sampled at baseline and after 1, 2, 4, 12 and 26 weeks. The
      clinical end-points were pocket-probing depth (PPD), plaque index (PI) and
      bleeding on probing (BOP). In addition, the subgingival microbiota was processed
      with checkerboard DNA-DNA hybridization and samples of gingival crevicular fluid
      (GCF) were analyzed for selected cytokines with the aid of multiplex
      immunoassays. RESULTS: After 4 and 12 weeks, all clinical parameters were
      improved in both the test and the placebo group. PPD and BOP were significantly
      reduced compared with baseline (p < 0.05), but no significant differences were
      displayed between the groups. The clinical improvements persisted 3 months after
      the intervention. No major alterations of the subgingival microflora were
      disclosed and the levels of inflammatory mediators in GCF did not differ between
      the groups. CONCLUSIONS: Mechanical debridement and oral hygiene reinforcement
      resulted in clinical improvement of peri-implant mucositis and a reduction in
      cytokine levels. Probiotic supplements did not provide added benefit to placebo.

PMID- 25953194
TI  - Systematic Comparison and Validation of Quantitative Real-Time PCR Methods for
      the Quantitation of Adeno-Associated Viral Products.
AB  - Adeno-associated viral (AAV) vectors show great promise for gene therapy because
      of their excellent safety profile; however, development of robust dose
      determining assays for AAV has presented a significant challenge. With the
      ultimate goal of future harmonization and standardization of AAV dose
      determination assays, we systematically analyzed the influence of key variables,
      including sample preparation procedure, the choice of primers, and real-time
      quantitative PCR (qPCR) target sequences and calibration DNA conformation on the
      qPCR quantitation of AAV products. Our results emphasize the importance of
      designing qPCR primers and conducting sample preparation and demonstrate the need
      for extensive characterization, vigorous control, and use of reference materials
      in clinical dose determination. 

PMID- 25953196
TI  - Pathological characterization of primary splenic myxoid liposarcomas in three
      dogs.
AB  - Non-angiomatous-non-lymphomatous sarcomas (NANLs) represent 23%-34% of canine
      primary splenic sarcomas. Splenic liposarcomas account for 2%-6% of NANLs but
      myxoid variants are rarely reported and information on their behaviour is
      fragmentary. An 8-year-old male crossbreed (case 1), a 12-year-old female French
      bulldog (case 2), and an 11-year-old crossbreed (case 3) underwent splenectomy
      after the detection of a splenic nodule. Histology, histochemistry,
      immunohistochemistry, and transmission electron microscopy (TEM) were performed.
      Bundles of spindle-to-polygonal cells containing occasional cytoplasmic oil-red-O
      positive vacuoles embedded in an Alcian blue-positive extracellular matrix were
      observed. Aggregates of round cells were detected in cases 1 and 3. All tumours
      were vimentin positive and actin, desmin, Factor VIII, and S100 negative. The TEM
      evidenced different maturational stages of adipose cells (lipoblasts,
      intermediate, and undifferentiated). All the cases developed hepatic metastases
      and were euthanized. Disease free interval was 2 months in cases 1 and 3, and 21
      months in case 2. The presence of a neoplastic embolus in case 1 and areas of
      round cell differentiation in cases 1 and 3 represented the sole prognostic
      indices. 

PMID- 25953195
TI  - Characteristics and role in outcome prediction of continuous EEG after status
      epilepticus: A prospective observational cohort.
AB  - OBJECTIVE: Continuous electroencephalography (cEEG) is important for treatment
      guidance in status epilepticus (SE) management, but its role in clinical outcome
      prediction is unclear. Our aim is to determine which cEEG features give
      independent outcome information after correction for clinical predictor. METHODS:
      cEEG data of 120 consecutive adult patients with SE were prospectively collected
      in three academic medical centers using the 2012 American Clinical
      Neurophysiology Society's Standardized Critical Care EEG Terminology. Association
      between cEEG features and two clinical outcome measures (mortality and complete
      recovery) was assessed. RESULTS: In the first 24 h of EEG recording, 49 patients
      (40.8%) showed no periodic or rhythmic pattern, 45 (37.5%) had periodic
      discharges, 20 (16.7%) had rhythmic delta activity, and 6 (5%) had spike-and-wave
      discharges. Seizures were recorded in 68.3% of patients. After adjusting for
      known clinical predictive factors for mortality including the STatus Epilepticus
      Severity Score (STESS) and the presence of a potentially fatal etiology, the only
      EEG features (among rhythmic and periodic patterns, seizures, and background
      activity) that remained significantly associated with outcome were the absence of
      a posterior dominant rhythm (odds ratio [OR] 9.8; p = 0.033) for mortality and
      changes in stage II sleep pattern characteristics (OR 2.59 for each step up among
      these categories: absent, present and abnormal, present and normal; p = 0.002)
      for complete recovery. SIGNIFICANCE: After adjustment for relevant clinical
      findings, including SE severity and etiology, cEEG background information
      (posterior dominant rhythm and sleep patterns) is more predictive for clinical
      outcome after SE than are rhythmic and periodic patterns or seizures.

PMID- 25953197
TI  - Impact of nitrogen deposition on forest and lake food webs in nitrogen-limited
      environments.
AB  - Increased reactive nitrogen (Nr ) deposition has raised the amount of N available
      to organisms and has greatly altered the transfer of energy through food webs,
      with major consequences for trophic dynamics. The aim of this review was to: (i)
      clarify the direct and indirect effects of Nr deposition on forest and lake food
      webs in N-limited biomes, (ii) compare and contrast how aquatic and terrestrial
      systems respond to increased Nr deposition, and (iii) identify how the nutrient
      pathways within and between ecosystems change in response to Nr deposition. We
      present that Nr deposition releases primary producers from N limitation in both
      forest and lake ecosystems and raises plants' N content which in turn benefits
      herbivores with high N requirements. Such trophic effects are coupled with a
      general decrease in biodiversity caused by different N-use efficiencies; slow
      growing species with low rates of N turnover are replaced by fast-growing species
      with high rates of N turnover. In contrast, Nr deposition diminishes below-ground
      production in forests, due to a range of mechanisms that reduce microbial
      biomass, and decreases lake benthic productivity by switching herbivore growth
      from N to phosphorus (P) limitation, and by intensifying P limitation of benthic
      fish. The flow of nutrients between ecosystems is expected to change with
      increasing Nr deposition. Due to higher litter production and more intense
      precipitation, more terrestrial matter will enter lakes. This will benefit
      bacteria and will in turn boost the microbial food web. Additionally, Nr
      deposition promotes emergent insects, which subsidize the terrestrial food web as
      prey for insectivores or by dying and decomposing on land. So far, most studies
      have examined Nr -deposition effects on the food web base, whereas our review
      highlights that changes at the base of food webs substantially impact higher
      trophic levels and therefore food web structure and functioning. 

PMID- 25953198
TI  - Single-molecule analysis of myocyte differentiation reveals bimodal lineage
      commitment.
AB  - Cell differentiation is the foundation for tissue development and regeneration,
      disease modeling, and cell-based therapies. Although the differentiation of cell
      populations has been extensively studied in many systems, much less is known
      about the distribution of decision making of single cells within these
      populations. To characterize the differentiation of single skeletal muscle cells,
      we used single-molecule mRNA fluorescence in situ hybridization (smFISH) to
      precisely quantify the expression levels of the master myogenic regulatory
      factors MyoD and myogenin in individual myoblasts. We identified distinct cell
      states characterized by the number of myogenin transcripts expressed by a cell,
      with myoblasts stochastically transitioning to a myogenin-high state during
      differentiation. We also used MyoD overexpression to force the
      transdifferentiation of C3H10T1/2 cells into an induced myoblast phenotype. These
      reprogrammed cells revealed the presence of a critical threshold of MyoD
      expression required to initiate myogenin expression. These results provide
      quantitative single-molecule data to support the model of switch-like cell
      decision making and lineage specification. 

PMID- 25953199
TI  - Smoking, central adiposity, and poor glycemic control increase risk of hearing
      impairment.
AB  - OBJECTIVES: To determine associations between smoking, adiposity, diabetes
      mellitus, and other risk factors for cardiovascular disease (CVD) and the 15-year
      incidence of hearing impairment (HI). DESIGN: A longitudinal population-based
      cohort study (1993-95 to 2009-10), the Epidemiology of Hearing Loss Study (EHLS).
      SETTING: Beaver Dam, Wisconsin. PARTICIPANTS: Participants in the Beaver Dam Eye
      Study (1988-90; residents of Beaver Dam, WI, aged 43-84 in 1987-88) were eligible
      for the EHLS. There were 1,925 participants with normal hearing at baseline.
      MEASUREMENTS: Fifteen-year cumulative incidence of HI (pure-tone average of
      hearing thresholds at 0.5, 1, 2, and 4 kHz greater than 25 decibels hearing level
      in either ear). Cigarette smoking, exercise, and other factors were ascertained
      according to questionnaire. Blood pressure, waist circumference, body mass index,
      and glycosylated hemoglobin were measured. RESULTS: Follow-up examinations (>=1)
      were obtained from 87.2% (n=1,678; mean baseline age 61). The 15-year cumulative
      incidence of HI was 56.8%. Adjusting for age and sex, current smoking (hazard
      ratio (HR)=1.31, P=.048), education (<16 years; HR=1.35, P=.01), waist
      circumference (HR=1.08 per 10 cm, P=.02), and poorly controlled diabetes mellitus
      (HR=2.03, P=.048) were associated with greater risk of HI. Former smokers and
      people with better-controlled diabetes mellitus were not at greater risk.
      CONCLUSION: Smoking, central adiposity, and poorly controlled diabetes mellitus
      predicted incident HI. These well-known risk factors for CVD suggest that
      vascular changes may contribute to HI in aging. Interventions targeting
      reductions in smoking and adiposity and better glycemic control in people with
      diabetes mellitus may help prevent or delay the onset of HI.

PMID- 25953200
TI  - Omapatrilat: penetration across the blood-brain barrier and effects on ischaemic
      stroke in rats.
AB  - Omapatrilat (OMA), which simultaneously inhibits the angiotensin-converting
      enzyme (ACE) and the neutral endopeptidase (neprilysin (NEP)), is widely used in
      experimental protocols related to hypertension and heart failure. The penetration
      of OMA across the blood-brain barrier (BBB) and the effects of ACE/NEP inhibition
      on the recovery from ischaemic stroke have not yet been investigated. Angiotensin
      (Ang) I injected intracerebroventricularly (ICV) or intravenously (IV) is
      converted to Ang II by ACE and induces an immediate increase in blood pressure.
      The pressor responses to OMA administered ICV, orally or IV were studied in male
      Wistar rats instrumented with an ICV and arterial and venous catheters. OMA
      infused ICV rapidly appeared in the systemic circulation and more effectively
      attenuated the systemic than the central pressor responses to Ang I. OMA
      administered orally (5, 25, 100 MUmol/kg body weight) or IV (0.5, 1, 5, 25
      MUmol/kg body weight) completely abolished increases in blood pressure to IV Ang
      I up to 2 h after treatment. The pressor responses to ICV Ang I were not altered,
      indicating that systemically administered OMA does not cross the BBB. To study
      the effects of ACE and NEP inhibition in the brain on the recovery from ischaemic
      stroke, OMA was infused ICV over a 5-day period before and 24 h after the
      occlusion of the middle cerebral artery (MCAO) for 90 min. ICV application of OMA
      had no effect on infarction volume and marginally improved neurological outcome.
      We demonstrate for the first time that simultaneous inhibition of ACE and NEP in
      the brain tissue does not alter the recovery from ischaemic stroke. 

PMID- 25953201
TI  - S100A8, An Oocyte-Specific Chemokine, Directs the Migration of Ovarian Somatic
      Cells During Mouse Primordial Follicle Assembly.
AB  - In the mammalian ovaries, the primordial follicle pool determines the
      reproductive capability over the lifetime of a female. The primordial follicle is
      composed of two cell members, namely the oocyte and the pre-granulosa cells that
      encircle the oocyte. However, it is unclear what factors are involved in the
      reorganization of the two distinct cells into one functional unit. This study was
      performed to address this issue. Firstly, in an in vitro reconstruction system,
      dispersed ovarian cells from murine fetal ovaries at 19.0 days post coitum (dpc)
      reassembled into follicle-like structures, independent of the physical distance
      between the cells, implying that either oocytes or ovarian somatic cells (OSCs)
      were motile. We then carried out a series of transwell assay experiments, and
      determined that it was in fact 19.0 dpc OSCs (as opposed to oocytes), which
      exhibited a significant chemotactic response to both fetal bovine serum and
      oocytes themselves. We observed that S100A8, a multi-functional chemokine, may
      participate in the process as it is mainly expressed in oocytes within the
      cysts/plasmodia. S100A8 significantly promoted the number of migrating OSCs by
      2.5 times in vitro, of which 66.9% were FOXL2 protein-positive cells, implying
      that the majority of motile OSCs were pre-granulosa cells. In addition, an S100A8
      specific antibody inhibited the formation of follicle-like reconstruction cell
      mass in vitro. And, the primordial follicle formation was reduced when S100a8
      specific siRNA was applied onto in vitro cultured 17.5 dpc ovary. Therefore,
      S100A8 could be a chemokine of oocyte origin, which attracts OSCs to form the
      primordial follicles.

PMID- 25953202
TI  - The Dilemma of Management of Prosthetic Valve Thrombosis: Thrombolysis or
      Surgery.

PMID- 25953203
TI  - Development of a ubiquitously transferrable silver-nanoparticle-loaded polymer
      nanosheet as an antimicrobial coating.
AB  - Ultra-thin polymer films (nanosheets) fabricated by a layer-by-layer (LbL) method
      possess unique properties such as high flexibility, adhesive strength, and
      transparency, and can be peeled off from a substrate and attached to various
      surfaces via a water-soluble supporting film. Therefore, flexible and
      transferrable LbL nanosheets are convenient tools as coating materials. Here, we
      fabricated a novel antimicrobial coating material by embedding silver
      nanoparticles (AgNPs) in an LbL nanosheet composed of layers of chitosan and
      sodium alginate (Ag-LbL nanosheet) by means of a photo-reduction method.
      Optimizing the amount of irradiated energy applied led to robust antimicrobial
      efficacy against methicillin-resistant Staphylococcus aureus (MRSA), sufficient
      to meet ISO standards (ISO 22196), while maintaining the flexibility and adhesive
      potency of the LbL nanosheet. Thus, the Ag-LbL nanosheet is a promising coating
      material that can provide antimicrobial efficacy to various surfaces.

PMID- 25953204
TI  - An Injectable, Self-Healing Hydrogel to Repair the Central Nervous System.
AB  - An injectable, self-healing hydrogel (~1.5 kPa) is developed for healing nerve
      system deficits. Neurosphere-like progenitors proliferate in the hydrogel and
      differentiate into neuron-like cells. In the zebrafish injury model, the central
      nervous system function is partially rescued by injection of the hydrogel and
      significantly rescued by injection of the neurosphere-laden hydrogel. The self
      healing hydrogel may thus potentially repair the central nervous system. 

PMID- 25953205
TI  - Evaluation of PICC complications in orthopedic inpatients with bone infection for
      long-term intravenous antibiotics therapy.
AB  - PURPOSE: The purpose of this study is to evaluate the complications of
      peripherally inserted central catheters (PICCs) in orthopedic patients with
      chronic bone orthopedic infection. MATERIALS AND METHODS: The institutional
      review board approved this retrospective study and informed consent was waived.
      Records of 180 consecutives PICCs placed in patients hospitalized in the
      orthopedic surgery department were reviewed. All patients had bones infections
      necessitating a long-term intravenous antibiotics therapy. All PICC complications
      were recorded during the patient hospitalization: infection [catheter-related
      bloodstream infection (CRBSI), central line associated bloodstream infection
      (CLABSI), exit-site infection, septic phlebitis], thrombosis, occlusion,
      mechanical complication (accidental withdrawal, malposition, median nerve
      irritation). RESULTS: One hundred and eighty PICCs were placed in 136 patients.
      Mean duration of catheterization was 21 days (total 3911 PICC-days). Thirty-six
      PICCs (20%) were removed due to complications (9.2 complications per 1000 PICC
      days): 14 (8%) infections (one CRBSI (Pseudomonas aeruginosa), one septic
      phlebitis (P. aeruginosa), two exit-site infections and 10 CLABSIs), 11 (6%)
      occlusions, and 12 (7%) mechanical complications (10 accidental withdrawals, one
      malposition, one median nerve irritation). One patient had two complications
      simultaneously. After multivariate analysis, two risk factors were significantly
      associated with the overall occurrence of complications: age more than 70 years
      [OR = 2.89 (1.06-7.89], p = 0.04] and number of lumen at least two [OR = 2.64
      (1.03-6.75), p = 0.04]. CONCLUSIONS: Even in orthopedic patients with chronic
      orthopedic bone infection, PICCs have a low rate of complication. The increasing
      lumen number of the PICC is a potential risk factor in our series.

PMID- 25953206
TI  - Proper tip position of central venous catheter in pediatric patients.
AB  - BACKGROUND: In this study, we analyzed the thin-section pulmonary computed
      tomographic (CT) angiogram scans of pediatric patients to determine the normative
      length of superior vena cava (SVC) and the distance between carina and cephalad
      of SVC or cavocatrial junction. METHODS: Consecutive child patients, under 13
      years of age in whom the central catheters were inserted under ultrasound
      guidance from December 2004 to April 2005 were evaluated retrospectively.
      RESULTS: In the 14 cases, the mean age was 7.2 +/- 4.21 years. The mean length
      and diameter of the SVC in the pediatric patients were 45.6 +/- 23.03 and 13.7 +/
      3.62 mm, respectively. The distance from the carina to the cavoatrial junction
      was 22.0 +/- 9.98 mm. The mean distance from the superior margin of the SVC to
      the carina was 23.7 +/- 16.70 mm. The mean distance from the carina to the
      catheter tip was 38.9 +/- 18.60 mm. In no case was the cavoatrial junction
      cephalad with respect to the carina. Carina to cavoatrial junction junction was
      significantly associated with age, height, and weight, respecitively (r = 0.750;
      p = 0.005, r = 0.763; p = 0.004; r = 0.777; p = 0.003). CONCLUSIONS: The carina
      is a good landmark for the upper border of the cavoatrial junction. Length of
      carina to cavoaterial juction was associated with age. The rates of malposition
      and re-intervention and the patient's exposure to radiation can be reduced by
      using ultrasound during the catheter insertion.

PMID- 25953207
TI  - Peroperative electrocardiographic control of catheter tip position during
      implantation of femoral venous ports.
AB  - PURPOSE: Electrocardiographic (ECG) guidance has been shown to be as effective
      than fluoroscopy to position the tip of central venous devices close to the
      superior vena cava (SVC)-right atrium (RA) junction. When SVC access is
      contraindicated, a femoral access may be used. The aim of this prospective study
      is to evaluate the effectiveness of ECG guidance to position the tip of femoral
      ports at inferior vena cava (IVC)-RA junction. METHODS: Inclusion criterion was
      the need for femoral port implantation. After insertion of the dilator in the
      femoral vein, the catheter with the guide wire inside was introduced and the ECG
      signal collected at the tip of the guide (CelsiteTM ECG, B. Braun, Germany) or
      via saline injected in the catheter (NautilusTM, Perouse, France). Fluoroscopy
      was performed at each change of the P-wave from IVC to RA. A final X-ray was
      performed after withdrawing the catheter 2 cm below the first P-wave change.
      RESULTS: A total of 18 patients were included between December 2011 and June
      2013. The P-wave was most often negative in IVC, biphasic when the catheter
      entered RA and giant and positive at the top of RA. When the catheter was
      withdraw 2 cm below the first biphasic P-wave the tip was just below the IVC-RA
      junction in 17 patients. In one patient P-wave changes were not significant and
      the final position was adjusted under fluoroscopy. CONCLUSIONS: ECG guidance is
      effective to assess catheter tip position during femoral port placement and
      avoids the need for radiological methods.

PMID- 25953208
TI  - Azygos vein thrombosis secondary to a peripherally inserted central catheter
      (PICC).
AB  - PURPOSE: This case illustrates a rare complication of a peripherally inserted
      central catheter (PICC). PICCs are associated with a significantly increased risk
      of upper extremity deep vein thrombosis; however, there are currently no case
      reports of isolated thrombosis of the azygos vein secondary to a PICC.
      CONCLUSIONS: With the well-documented increase in the use of PICCs for venous
      access we remind clinicians to consider this rare complication.

PMID- 25953209
TI  - The stuck catheter: a hazardous twist to the meaning of permanent catheters.
AB  - INTRODUCTION: Permanent central venous catheter use is associated with
      significant complications that often require their timely removal. An uncommon
      complication is resistant removal of the catheter due to adherence of the
      catheter to the vessel wall. This occasionally mandates invasive interventions
      for removal. The aim of this study is to describe the occurrence of this "stuck
      catheter" phenomenon and its consequences. METHODS: A retrospective review of all
      the removed tunneled hemodialysis catheters from July 2005 to December 2014 at a
      single academic-based hemodialysis center to determine the incidence of stuck
      catheters. Data were retrieved from a prospectively maintained computerized
      vascular access database and verified manually against patient charts. RESULTS:
      In our retrospective review of tunneled hemodialysis catheters spanning close to
      a decade, we found that 19 (0.92%) of catheters were retained, requiring
      endovascular intervention or open sternotomy. Of these, three could not be
      removed, with one patient succumbing to catheter-related infection. Longer
      catheter vintage appeared to be associated with 'stuck catheter'. CONCLUSIONS:
      Retention of tunneled central venous catheters is a rare but important
      complication of prolonged tunneled catheter use that nephrologists should be
      aware of. Endoluminal balloon dilatation procedures are the initial approach, but
      surgical intervention may be necessary.

PMID- 25953210
TI  - Ultrasound evaluation of saphenous vein for peripheral intravenous cannulation in
      adults.
AB  - OBJECTIVES: The objective of this study was to investigate variables that may
      affect sonographic cannulation of great saphenous vein and determine the ideal
      location for ultrasound-guided saphenous vein cannulation in adult emergency
      department (ED) patients. METHODS: A prospective observational study at an
      academic ED. The great saphenous vein was identified in adult subjects at three
      distinct sites after placing the tourniquet proximal to the vein: the ankle, mid
      calf, and below the knee using a 10-5 MHz linear transducer. The depth of the
      saphenous vein from the skin surface and its diameter were measured in supine and
      reverse trendelenburg positions in both extremities. RESULTS: A total of 60
      subjects (male 30, female 30) were enrolled in the study. The median age of the
      patients was 50.5 years [interquartile range (IQR) 34.5-67.5]. The median body
      mass index (BMI) was 27.3 (IQR, 24.2-31.8). The great saphenous vein was
      significantly superficial in location at the ankle level compared with the calf
      (p<0.001), knee (p<0.001), and left side compared with the right (p<0.001). The
      subject position was not significantly related to saphenous vein depth (p =
      0.68). The saphenous vein diameter was significantly larger in the left lower
      extremity than the right side (p = 0.007), and at the ankle level compared with
      the calf (p<0.001) and knee (p<0.001). The diameter of the vein increased
      significantly when patient's position changed from supine to reverse
      Trendelenburg (p<0.001). CONCLUSIONS: Our results support ultrasound evaluation
      of the course of great saphenous vein from the ankle to the knee for the
      selection of appropriate venipuncture site and cannulation.

PMID- 25953211
TI  - Early access ligation resolves presumed ischaemic monomelic neuropathy in a
      patient with recurrence of central venous occlusion.
AB  - PURPOSE: Ischaemic monomelic neuropathy (IMN) is a rare but serious complication
      of haemodialysis access procedures, with a highly variable clinical presentation.
      We present a case of presumed IMN managed with ligation of the prosthetic
      brachial-axillary access, leading to recovery of neurological function. METHODS:
      A 75-year-old male who underwent placement of a left prosthetic brachial-axillary
      access developed a swollen left upper limb following surgery and underwent
      interventional management for central venous occlusion. RESULTS: Eleven weeks
      following placement of the access, he presented with gross swelling and loss of
      function in the left arm. Ultrasonography excluded nerve compression. The
      brachial-axillary access was urgently ligated, leading to recovery of function in
      the arm. Electromyography (EMG) studies confirmed an ischaemic cause.
      CONCLUSIONS: The pathophysiology of IMN is poorly understood. This case is
      atypical in that the patient suffered from central venous stenosis prior to the
      development of IMN. This raises the possibility that the gross swelling secondary
      to recurrent central venous occlusion may have led to an ischaemic neuropathy by
      altering nerve perfusion. Early management led to a functional recovery of the
      affected limb, suggesting that an urgent approach in patients with suspected IMN
      might be associated with the best outcomes.

PMID- 25953212
TI  - Innominate vein stenosis in breast cancer patients after totally implantable
      venous access port placement.
AB  - PURPOSE: To evaluate the risk factors for central vein stenosis after placement
      of the totally implantable venous access ports (TIVPs) and the clinical relevance
      of this condition in breast cancer patients. MATERIALS AND METHODS: TIVPs were
      placed in 191 women with breast cancer via the internal jugular vein (IJV) from
      January 2009 to December 2012 (mean age, 51.42 years) by left-side (n = 102) and
      right-side (n = 89) approaches. Medical records were retrospectively reviewed.
      The presence of significant central vein stenosis, tip location of the catheter
      and retrosternal space were evaluated on chest computed tomography images.
      Statistical analysis was performed. RESULTS: Central vein stenosis developed in 1
      and 14 patients after placement via the right and left IJV, respectively.
      Differences in the cumulative incidence of central vein stenosis were
      statistically significant between left- and right-side approach groups (log rank
      test p-value: 0.009). In Cox regression analysis, the hazard ratio for central
      vein stenosis was 9.441 (p = 0.031) in the left-side approach. The distance
      between the sternum and the left innominate vein was found to be significantly
      and independently related to the development of central vein stenosis (p =
      0.026). The hazard ratio of distances between the sternum and left innominate
      vein lt;16 mm was 10.133 (1.319-77.841). CONCLUSIONS: The incidence of central
      vein stenosis in breast cancer patients was higher after placement of TIVPs via
      the left IJV. When left-side TIVP placement is required in a patient with right
      side breast cancer, the possibilities of left innominate vein stenosis should be
      considered.

PMID- 25953213
TI  - An open, prospective trial investigating the pharmacokinetics and safety, and the
      tolerability of escalating infusion rates of a 10% human normal immunoglobulin
      for intravenous infusion (IVIg), BT090, in patients with primary immunodeficiency
      disease.
AB  - BACKGROUND AND OBJECTIVES: Pharmacokinetics, safety and tolerability of
      escalating infusion rates of BT090, a 10% intravenous immunoglobulin (IVIg), were
      studied in patients with primary immunodeficiency disease. MATERIALS AND METHODS:
      In Part A, patients (n = 30) received 3 infusions of BT090 at their pretrial dose
      and dosing interval; the infusion rate of BT090 was increased from 0.3 to 1.4 to
      2.0 ml/kg/h for each infusion in each patient initially at 30-min intervals.
      Pharmacokinetics was evaluated at the 3rd infusion (n = 24). At the 4th infusion,
      infusion rates were to be gradually escalated from 0.3 to 1.4 to 4.0 to a maximum
      of 8.0 ml/kg/h initially at 30-min intervals to establish the maximum tolerated
      infusion rate per patient. RESULTS: The pharmacokinetic characteristics and
      safety profile of BT090 were comparable with those of other IVIgs, including
      Intratect((r)) . Escalation of infusion rates was well tolerated, allowing
      identification of individual patient's maximum tolerated infusion rate. At
      subsequent infusions, all patients tolerated their individually defined maximum
      infusion rate: 17 patients (68.0%) tolerated infusion rates of 6.0 or 8.0 ml/kg/h
      and four patients (16%) had maximum tolerated infusion rates of <4.0 ml/kg/h at
      subsequent infusions. Escalation of infusion rates shortened infusion time from a
      median of around 2.5 h to around 1.6 h. SAEs were reported in three patients, but
      none was related to BT090 treatment. CONCLUSIONS: Shortening infusion time may
      reduce overall healthcare spending, for example nursing time needed, and also
      minimize disruption of patients' daily routine, especially for those patients in
      work or school settings.

PMID- 25953214
TI  - Fluoroscopy-guided thrombolysis of mechanical mitral valve thrombosis in a young
      female with antiphospholipid antibody syndrome.
AB  - Prosthetic valve thrombosis (PVT) is a rare but potentially fatal complication of
      mechanical valve prosthesis. The differential diagnoses for prosthetic valve
      obstruction includes pannus formation, prosthetic valve dehiscence, prosthetic
      valve endocarditis, chordae entrapment, patient-prosthesis mismatch and primary
      device failure. Establishing a diagnosis requires an understanding of prosthetic
      valve haemodynamics and careful correlation of clinical and imaging findings.
      Definitive therapy must be individualised based on various patient-specific
      factors. We present a case of mechanical mitral PVT in a young woman with
      antiphospholipid antibody syndrome, and outline the diagnostic and therapeutic
      approach utilised for successful treatment. The success and complication rates of
      various therapeutic strategies are also discussed, and highlight the need for
      individualised decision-making rather than a one-size-fits-all approach to PVT. 

PMID- 25953215
TI  - Fetal programming in meat production.
AB  - Nutrient fluctuations during the fetal stage affects fetal development, which has
      long-term impacts on the production efficiency and quality of meat. During the
      early development, a pool of mesenchymal progenitor cells proliferate and then
      diverge into either myogenic or adipogenic/fibrogenic lineages. Myogenic
      progenitor cells further develop into muscle fibers and satellite cells, while
      adipogenic/fibrogenic lineage cells develop into adipocytes, fibroblasts and
      resident fibro-adipogenic progenitor cells. Enhancing the proliferation and
      myogenic commitment of progenitor cells during fetal development enhances muscle
      growth and lean production in offspring. On the other hand, promoting the
      adipogenic differentiation of adipogenic/fibrogenic progenitor cells inside the
      muscle increases intramuscular adipocytes and reduces connective tissue, which
      improves meat marbling and tenderness. Available studies in mammalian livestock,
      including cattle, sheep and pigs, clearly show the link between maternal
      nutrition and the quantity and quality of meat production. Similarly, chicken
      muscle fibers develop before hatching and, thus, egg and yolk sizes and hatching
      temperature affect long-term growth performance and meat production of chicken.
      On the contrary, because fishes are able to generate new muscle fibers lifelong,
      the impact of early nutrition on fish growth performance is expected to be minor,
      which requires further studies. 

PMID- 25953216
TI  - Kif20a inhibition reduces migration and invasion of pancreatic cancer cells.
AB  - BACKGROUND: The Translational Genome Research Network in Pancreatic Cancer
      performed a meta-analysis of publicly available various high-throughput gene
      analysis panels to identify drugable targets. There, the most differentially
      expressed gene between normal and cancerous pancreas was Kif20a. The aim of the
      study was to verify this expression pattern and further characterize Kif20a in
      pancreatic cancer. MATERIALS AND METHODS: Detailed expression analyses were
      carried out in pancreatic tissues and in a wide panel of pancreatic cells
      including ductal adenocarcinoma (PDAC) and neuroendocrine-cancer cell lines as
      well as immortalized human pancreatic ductal epithelial and primary stellate
      cells using quantitative real-time polymerase chain reaction,
      immunohistochemistry, immunofluorescence, and immunoblot analyses. Effects on
      proliferation, apoptosis, and cell cycle were assessed by MTT assays, caspase
      cleavage assays, and fluorescence-activated cell sorting analysis after Kif20a
      silencing. Cell motility was assessed by migration and invasion assays as well as
      time-lapse microscopy. RESULTS: Mean Kif20a messenger RNA expression was 18.4
      fold upregulated in PDAC tissues compared with that in the normal pancreas. In
      line, neuroendocrine-cancer cell lines display a 1.6-fold increase and ductal
      adenocarcinoma cell lines a 11-fold increase of Kif20a messenger RNA (P = 0.009)
      in comparison with primary stellate cells. A 7.3-fold overexpression was also
      found in immortalized pancreatic ductal epithelial cells. Kif20a silencing with
      small interfering RNA molecules resulted in an inhibition of proliferation,
      motility, and invasion of pancreatic cancer cell lines. CONCLUSIONS: Targeting
      Kif20a reduces proliferation, migration, and invasion of pancreatic cancer cells.
      Together with its significant overexpression in PDAC, this makes it a potential
      target for diagnostic and interventional purposes.

PMID- 25953217
TI  - The diagnostic pathway for solid pancreatic neoplasms: are we applying too many
      tests?
AB  - BACKGROUND: The single best diagnostic and staging test for pancreatic cancer
      remains a contrast-enhanced computed tomography scan. It is frequently the only
      imaging test required before surgical resection for solid pancreatic lesions.
      Unfortunately, many patients undergo additional testing that often delays
      definitive care. MATERIALS AND METHODS: A retrospective review of all patients
      with solid pancreatic lesions concerning for adenocarcinoma referred to a high
      volume Hepato-Pancreato-Biliary (HPB) service over 4 y (2008-2012) was completed.
      The time intervals between the initial imaging test and both consultation with
      HPB surgery and operative intervention, as well as the number of additional
      tests, were evaluated. Standard statistical methodology was used (P < 0.05).
      RESULTS: Among 130 patients with solid pancreatic lesions, the index imaging
      modality was ultrasonography and computed tomography for 75 (58%) and 52 (40%),
      respectively. Patients underwent a mean of 1.3 diagnostic tests after the index
      study and before consultation with HPB surgery (range: 0-5). There was a
      significant increase in time to HPB consultation and operative intervention with
      an increasing number of interval imaging tests. The mean time to surgical
      consultation and operation if 0 interval diagnostic tests were performed was 15.9
      and 45.4 d, respectively. If four interval tests were conducted, the mean was
      69.4 and 122.6 d, respectively. Sixty-two patients (48%) were initially referred
      to a nonsurgical service. The mean time to surgical consultation and operation if
      an intervening referral occurred was 36.6 and 66.8 d, respectively. This compares
      to 19.8 and 48.1 d, respectively, in cases of direct referral to an HPB surgeon.
      The mean number of diagnostic tests performed before HPB consultation if a
      nonsurgical referral occurred was 2.1 (versus 0.7 if direct HPB surgeon
      referral). CONCLUSIONS: Despite a relatively simple algorithm for the
      investigation of solid pancreatic lesions, considerable heterogeneity remains in
      how these patients are evaluated before referral to HPB surgery. As the number of
      investigations increases after the index imaging test, there is increasing delay
      to both surgical consultation and definitive intervention. Education is required
      to expedite care and mitigate excess diagnostic tests.

PMID- 25953219
TI  - Acromioclavicular joint reconstruction: complications and innovations.
AB  - Minimally invasive anatomic reconstruction of the acromioclavicular joint is a
      technically challenging procedure. The repair must be sufficiently strong and
      reconstitute the joint as closely as possible. This includes restoration of both
      superior-inferior stability, and the often overlooked anterior-posterior
      stability, of the acromioclavicular joint. There is no gold standard treatment
      for acromioclavicular joint separation. 

PMID- 25953220
TI  - Pedicled quadriceps graft or the superficial quad graft?

PMID- 25953218
TI  - MicroRNA-21 predicts response to preoperative chemoradiotherapy in locally
      advanced rectal cancer.
AB  - PURPOSE: The treatment of choice for locally advanced rectal cancer is
      preoperative chemoradiotherapy. Despite half of patients do not respond and
      suffer unnecessary toxicities and surgery delays, there are no biomarkers to
      guide preoperative CRT outcome. MicroRNA-21 has been related to acquisition of 5
      fluorouracil resistance; however, its potential predictive value of response to
      preoperative chemoradiotherapy in locally advanced rectal cancer remains unknown.
      METHODS: Nighty-two patients diagnosed with locally advanced rectal cancer who
      were preoperatively treated with chemoradiotherapy were selected for this study.
      Moreover, microRNA-21 expression was quantified in formalin-fixed paraffin
      embedded biopsies from this cohort, and the results obtained were correlated with
      clinical and molecular characteristics, pathological response, and outcome.
      RESULTS: MicroRNA-21 was found overexpressed in 77.6% cases, and significantly
      correlated with tumor grade after preoperative chemoradiotherapy (P = 0.013) and
      with pathological response (P = 0.013). The odds ratio of having miR-21
      overexpression and not getting a respond to chemoradiotherapy resulted in 9.75 CI
      2.24 to 42. Sensitivity, specificity, negative predictive values, and positive
      predictive value were 86.6, 60, 42.8, and 92%, respectively. Multivariate
      analysis confirmed the clinical significance of miR-21 determining preoperative
      chemoradiotherapy response. CONCLUSIONS: MicroRNA-21 expression efficiently
      predicts preoperative chemoradiotherapy pathological response in locally advanced
      rectal cancer.

PMID- 25953221
TI  - Author's reply: To PMID 24904782.

PMID- 25953223
TI  - Editorial commentary: meniscal allograft yields acceptable outcomes (for a
      salvage procedure).
AB  - Meniscal allograft, for proper indications, shows adequate outcomes (for a
      salvage procedure). Addition of biologics (growth factors and cells) may improve
      future outcomes, and ultimately a tissue-engineered solution is anticipated, but
      in the end, host articular cartilage pathology may be a significant confounder of
      outcome. 

PMID- 25953222
TI  - The effect of norepinephrine versus epinephrine in irrigation fluid on the
      incidence of hypotensive/bradycardic events during arthroscopic rotator cuff
      repair with interscalene block in the sitting position.
AB  - PURPOSE: To compare the occurrence rate of hypotensive and bradycardic events
      (HBEs) during arthroscopic rotator cuff repair performed with interscalene
      brachial plexus block anesthesia in the sitting position in 2 groups of patients
      who underwent the procedure with norepinephrine or epinephrine added to the
      irrigation fluid. The secondary objective was to evaluate the efficacy of
      norepinephrine in comparison with epinephrine in controlling intraoperative
      bleeding and maintaining adequate visualization of the arthroscopic field of view
      during the procedure. We hypothesized that norepinephrine added to the irrigation
      fluid during shoulder arthroscopy in the sitting position would reduce the
      occurrence of HBEs, allowing optimal intraoperative bleeding control. METHODS:
      One hundred twenty patients underwent an arthroscopic rotator cuff repair
      performed under peripheral anesthesia and in the beach-chair position. Patients
      were randomly divided into 2 groups of 60 cases each: Norepinephrine (0.66 mg/L)
      and epinephrine (0.33 mg/L) were added to irrigation bags in group N and group E,
      respectively. The primary outcome was the occurrence rate of HBEs during surgery.
      The secondary outcomes were timing of onset of HBEs, accompanying symptoms, and
      intraoperative bleeding that impaired arthroscopic visualization. The clarity of
      the visual field was rated postoperatively by the surgeon using a visual analog
      scale. Comparison between groups for all baseline variables and outcome
      measurements was performed with the chi(2) or Fisher exact test, as appropriate,
      for categorical variables and the Student t test or Mann-Whitney U test, as
      appropriate, for continuous variables. Significance was set at P < .05. RESULTS:
      One patient was excluded from group E because of block failure; therefore 119
      patients were finally included in the study. Comparison between groups showed no
      significant differences in baseline characteristics. The occurrence rate of HBEs
      was significantly greater in group E (n = 15) than in group N (n = 5) (P = .02).
      No differences between groups were found in the average time of onset of HBEs,
      accompanying symptoms, and clarity of the visual field. CONCLUSIONS: Continuous
      administration of norepinephrine, 0.66 mg/L, diluted in irrigation fluid during
      arthroscopic rotator cuff repair with the patient in the beach-chair position
      reduces the incidence of HBEs and is as effective as epinephrine in controlling
      intraoperative bleeding and maintaining the visual clarity of the surgical field.
      LEVEL OF EVIDENCE: Level I, randomized clinical study.

PMID- 25953224
TI  - Editorial commentary: collagen meniscal scaffolds.
AB  - Small collagen meniscal scaffolds are a treatment for partial meniscectomy, which
      is clinically much more common than subtotal or total meniscectomy. The scaffold
      alone shows promising results, but readers must be mindful of risk of bias in the
      literature. Addition of stem cells and growth factors is the next step in
      meniscal tissue engineering. 

PMID- 25953225
TI  - Editorial commentary: meniscal tissue engineering.
AB  - Meniscal tissue engineering requires cells, scaffolds, growth factors,
      biomechanical stimulation, and biochemical stimulation. Preclinical work is
      assiduous; however, we are today, unaware of any clinical reports of meniscal
      tissue engineering in the literature. 

PMID- 25953226
TI  - Editorial commentary: synthetic ACL grafts are more important than clinical
      nonbelievers may realize.
AB  - Artificial ACL grafts are structural ties, designed to resist tension, but not
      designed to undergo biologic ligamentization by the host. Strategically, an
      artificial ACL graft may be used as reinforcement to augment ACL repair, ACL
      autograft, ACL allograft, or tissue-engineered ACL. Most artificial ACL grafts
      have had poor reported outcomes. However, the Ligament Augmentation and
      Reconstruction System (LARS) artificial ACL graft shows positive clinical
      outcomes. 

PMID- 25953227
TI  - Editorial commentary: ACL tissue bioengineering clinical application is in its
      infancy.
AB  - Preclinical ACL tissue engineering studies show promise using a combination of
      cells, scaffolds, growth factors, and "stimulation," such as ultrasound or
      shockwave therapy, but clinical application is in its infancy. Bioactive
      scaffolds may be weak at time zero. A solution could be to add to the combination
      of cells, scaffolds, growth factors, simulation, and a structural tie. 

PMID- 25953228
TI  - Editorial commentary: platelet-rich plasma in ACL surgery.
AB  - Current literature does not suggest that PRP treatment improves ACL clinical
      outcomes. However, PRP preparations are heterogeneous, and PRP clinical
      investigation is affected by an infinite number of confounding variables. In
      addition, PRP is but one type of biologic stimulant. PRP may have benefits for
      ACL surgery, but clinical evidence is in its infancy. 

PMID- 25953229
TI  - Editorial commentary: ACL bioactive scaffold.
AB  - ACL bioactive scaffolds may be used to bioenhance ACL primary repair, and they
      show preclinical (porcine) promise. We are extremely interested in ongoing
      clinical development. 

PMID- 25953230
TI  - Editorial commentary: biologic enhancement of muscle and tendon healing.
AB  - Review of biologic enhancement of muscle and tendon healing reveals substantial
      clinical study of platelet rich plasma, but an inadequate basis for evidence
      based treatment recommendations. In this context, the literature shows that
      augmentation of rotator cuff repair is not shown to be of benefit, while
      treatment of knee and ankle tendinopathy and plantar fasciitis shows positive
      results. 

PMID- 25953231
TI  - Editorial commentary: tissue engineering in knee arthroscopic and related
      surgery.
AB  - Stem cells are guided by scaffolds, induced by growth factors, and stimulated by
      biomechanical forces, with a goal of engineering clinically competent cartilage,
      meniscus, tendon, or ligament tissue. Translational research, to move us from the
      preclinical to the clinical phase, is today necessary. 

PMID- 25953232
TI  - inv (4)(p13q13) in patient with essential thrombocythemia: A case report.
AB  - The inv (4)(p13q13) cytogenetic abnormality is uncommon in hematologic
      malignancies. So far, it has not been previously reported in patients with
      essential thrombocythemia (ET). We report a first case of ET with inv (4)(p13q13)
      karyotype in a 69-year-old female patient who developed myelofibrosis at follow
      up. Conventional cytogenetic analysis from a bone marrow sample showed 46, XX,
      inv (4)(p13q13) [3]/46, XX [4] at diagnosis and subsequent analysis revealed the
      same abnormal karyotype during the myelofibrosis phase (46, XX, inv (4)(p13q13)
      [13]/46, XX [26]). The prognostic significance of this chromosomal abnormality is
      unknown. 

PMID- 25953233
TI  - Composite angioimmunoblastic T-cell and diffuse large B-cell lymphoma.

PMID- 25953234
TI  - Welcome to the 11th International Conference on Pediatric Mechanical Circulatory
      Support Systems and Pediatric Cardiopulmonary Perfusion.

PMID- 25953235
TI  - The hidden limitations in "advertising" a novel synchronized cardiac assist
      device.

PMID- 25953236
TI  - Reply to letter: pulsatile venoarterial perfusion using a novel synchronized
      cardiac assist device augments coronary artery blood flow during ventricular
      fibrillation.

PMID- 25953239
TI  - Eighth Istanbul symposium on pediatric extracorporeal life support systems and
      pediatric cardiopulmonary perfusion.

PMID- 25953240
TI  - Letter on the article "Partial laryngectomy as salvage surgery after
      radiotherapy: oncological and functional outcomes and impact on quality of life.
      A retrospective study of 20 cases".

PMID- 25953242
TI  - The use of smartphones or tablets in surgery. What are the limits?

PMID- 25953243
TI  - Lessons learned from engaging men in sexual and reproductive health as clients,
      partners and advocates of change in the Hoima district of Uganda.
AB  - This study examined the impact of a three-year intervention project conducted in
      the Hoima district of Uganda, which sought to engage men in sexual and
      reproductive health as clients, equal partners and advocates of change.
      Structured surveys with 164 self-reported heterosexual men aged 18-54 years were
      used to assess knowledge and attitudes towards sexual and reproductive health.
      Data from these were analysed using Stata and SPSS. Additionally, five focus
      groups were conducted with the female partners and male beneficiaries of the
      project and with project peer educators. Four interviews were conducted with
      project staff and male beneficiaries. Data from these and the focus groups were
      analysed using a thematic approach. Following the intervention, a significantly
      greater number of men accessed, and supported their partners in accessing sexual
      health services services, had gained sexual and reproductive health awareness,
      reported sharing domestic duties and contraceptive decision-making, and displayed
      a decreased tolerance for domestic violence. It was more difficult to assess
      men's involvement and behaviours as advocates of change, which sheds light on the
      complexities of a gender transformative project and the importance of evaluating
      such projects from both men's and their partners' perspectives and at different
      levels of the male involvement model in sexual and reproductive health. 

PMID- 25953244
TI  - Sensory input to the central nervous system from the lungs and airways: A
      prominent role for purinergic signalling via P2X2/3 receptors.
AB  - Specific subpopulations of lung-related primary afferent neurons in dorsal root
      and vagal sensory ganglia have been reported to express P2X2 and P2X3 receptors
      both in the neuronal cell bodies and in their peripheral terminals. The afferent
      innervation of airways and lungs is organised as sensory receptor structures, of
      which at least seven types with a vagal origin and two with a spinal origin have
      been reported. In view of the recently suggested therapeutic promise of ATP
      antagonism - specifically at P2X3 receptor expressing nociceptive fibres - in
      respiratory disorders, the present work focusses on four distinct populations of
      pulmonary sensory receptors that have so far been reported to express P2X2/3
      receptors. Three of them originate from myelinated nerve fibres that display
      similar mechanosensor-like morphological and neurochemical characteristics. Two
      of the latter concern vagal nodose sensory fibres, either related to pulmonary
      neuroepithelial bodies (NEBs), or giving rise to smooth muscle-associated airway
      receptors (SMARs); the third gives rise to visceral pleura receptors (VPRs) and
      most likely arises from dorsal root ganglia. The fourth population concerns C
      fibre receptors (CFRs) that also derive from neuronal cell bodies located in
      vagal nodose ganglia. Although the majority of the airway- and lung-related
      sensory receptors that express P2X2/3 receptors apparently do not belong to
      accepted nociceptive populations, these data definitely point out that ATP may be
      an important player in the physiological transduction of different lung-related
      afferent signals from the periphery to the CNS. The observed variety within the
      populations of pulmonary sensory receptors that express P2X2/3 receptors argues
      for a critical and careful interpretation of the functional data. 

PMID- 25953241
TI  - Type I interferons regulate eomesodermin expression and the development of
      unconventional memory CD8(+) T cells.
AB  - CD8(+) T-cell memory phenotype and function are acquired after antigen-driven
      activation. Memory-like cells may also arise in absence of antigenic exposure in
      the thymus or in the periphery. Eomesodermin (Eomes) is a key transcription
      factor for the development of these unconventional memory cells. Herein, we show
      that type I interferon signalling in CD8(+) T cells directly activates Eomes gene
      expression. Consistent with this observation, the phenotype, function and age
      dependent expansion of 'virtual memory' CD8(+) T cells are strongly affected in
      absence of type I interferon signalling. In addition, type I interferons induce a
      sustained expansion of 'virtual memory' CD8(+) T cells in an Eomes-dependent
      fashion. We further show that the development of 'innate thymic' CD8(+) T cells
      is dependent on the same pathway. In conclusion, we demonstrate that type I
      interferon signalling in CD8(+) T cells drives Eomes expression and thereby
      regulates the function and homeostasis of memory-like CD8(+) T cells. 

PMID- 25953245
TI  - Purinergic signalling and development of the autonomic nervous system.
AB  - Most early studies of the role of nucleotides in development have evidenced their
      crucial importance as carriers of energy in all organisms. However, an increasing
      number of studies are now available to suggest that purines and pyrimidines,
      acting as extracellular ligands specifically on receptors of the plasma membrane,
      may play a pivotal role throughout pre- and postnatal development in a wide
      variety of organisms including amphibians, birds, and mammals. Purinergic
      receptor expression and functions have been studied in the development of many
      organs, including the autonomic nervous system (ANS). Nucleotide receptors can
      induce a multiplicity of cellular signalling pathways via crosstalk with
      bioactive molecules acting on growth factors and neurotransmitter receptors which
      are fundamental for the development of a mature and functional ANS. Purines and
      pyrimidines may influence all the stages of neuronal development, including
      neural cell proliferation, migration, differentiation and phenotype determination
      of differentiated cells. Indeed, the normal development of the ANS is disturbed
      by dysfunction of purinergic signalling in animal models. To establish the
      primitive and fundamental nature of purinergic neurotransmission in the ontogeny
      of the ANS, in this review the roles of purines and pyrimidines as signalling
      molecules during embryological and postnatal development are considered. 

PMID- 25953246
TI  - BAP1-deficient and VE1-negative atypical Spitz tumor.
AB  - Atypical Spitz tumor with loss of BAP1 or Wiesner nevus is a peculiar variant of
      intradermal spitzoid melanocytic neoplasm composed of epithelioid melanocytes
      with a sheet-like growth pattern, abundant infiltrating lymphocytes and rare or
      absent mitotic activity. This subset of atypical spitzoid tumors is characterized
      by the BRAF(V600E) mutation and loss of BAP1 expression. Recognition of these
      lesions is important because they can be a marker for a hereditary BAP1
      associated cancer syndrome. We present an unusual case of sporadic Wiesner nevus
      that had typical histopathologic features and a BAP1 but not a BRAF mutation. The
      biological significance of Wiesner nevus is controversial, and little is known
      about prognosis, particularly in atypical cases like this one. 

PMID- 25953247
TI  - Middle aortic syndrome--an 8-year story of pills, pretty balloons and struts.
AB  - BACKGROUND: Middle aortic syndrome (MAS) is an uncommon cause of hypertension in
      children. The management of hypertension secondary to MAS frequently requires
      several anti-hypertensive medications along with endovascular and often surgical
      intervention. CASE-DIAGNOSIS/TREATMENT: A 9-year-old boy presented with headaches
      and vomiting and was diagnosed with severe hypertension secondary to idiopathic
      MAS affecting a long segment of the abdominal aorta and left renal artery
      stenosis. Over the following 8 years his hypertension was successfully managed
      initially with percutaneous transluminal balloon angioplasty (PTA) of his left
      renal artery, followed by balloon dilatation of his abdominal aortic narrowing.
      He subsequently underwent abdominal aortic stent placement following failed
      repeat aortic balloon dilatation. Aged 17 years and 6 months he is now on a
      single anti-hypertensive agent with normal renal function and no evidence of
      target organ damage. CONCLUSION: In selected cases, MAS may be managed with PTA
      and stent placement with good long-term outcomes. Limited data on the use of PTA
      and stent insertion in children means that a structured approach to the
      management of refractory hypertension secondary to MAS remains elusive.

PMID- 25953248
TI  - The ameliorated longevity and pharmacokinetics of valsartan released from a gel
      system of ultradeformable vesicles.
AB  - OBJECTIVE: The present study traces the development and characterization of the
      gel formulation of valsartan-loaded ultradeformable vesicles for management of
      hypertension. MATERIALS AND METHODS: The prepared gel formulation of
      ultradeformable vesicles was evaluated for in vitro skin permeation, release
      kinetics, skin irritation, pharmacokinetics, and stability. RESULTS AND
      DISCUSSION: The in vitro skin permeation study showed that the gel formulation of
      ultradeformable vesicles presented a flux value of 368.74 MUg/cm(2)/h, in
      comparison to that of the traditional liposomal gel formulation, with an
      enhancement ratio of 26.91, through rat skin. The data for release kinetics
      showed that the release profile followed zero-order kinetics, and that the drug
      release mechanism was non-Fickian. The results of the skin irritation study
      demonstrated that the prepared formulation was safe, less irritant, and well
      tolerated for transdermal delivery. The results of the pharmacokinetic study
      demonstrated that the AUC value of valsartan after transdermal administration was
      apparently increased. The formulation stored under a refrigerated condition
      showed greater stability, and results were found to be within the specification
      under storage conditions. CONCLUSION: It is evident from this study that the gel
      formulation of ultradeformable vesicles of valsartan is a promising delivery
      system for lipophilic drugs, and has reasonably good stability characteristics.

PMID- 25953249
TI  - A case report and literature review of Fanconi Anemia (FA) diagnosed by genetic
      testing.
AB  - Fanconi anemia (FA) is a genetically heterogeneous rare autosomal recessive
      disorder characterized by congenital malformations, hematological problems and
      predisposition to malignancies. The genes that have been found to be mutated in
      FA patients are called FANC. To date 16 distinct FANC genes have been reported.
      Among these, mutations in FANCA are the most frequent among FA patients worldwide
      which account for 60- 65%. In this study, a nine years old male child was brought
      to our hospital one year ago for opinion and advice. He was the third child born
      to consanguineous parents. The mutation analyses were performed for proband,
      parents, elder sibling and the relatives [maternal aunt and maternal aunt's son
      (cousin)]. Molecular genetic testing [targeted next-generation sequencing (MiSeq,
      Illumina method)] was performed by mutation analysis in 15 genes involved. Entire
      coding exons and their flanking regions of the genes were analysed. Sanger
      sequencing [(ABI 3730 analyzer by Applied Biosystems)] was performed using
      primers specific for 43 coding exons of the FANCA gene. A novel splice site
      mutation, c.3066 + 1G > T, (IVS31 + 1G > T), homozygote was detected by
      sequencing in the patient. The above sequence variant was identified in
      heterozygous state in his parents. Further, the above sequence variant was not
      identified in other family members (elder sibling, maternal aunt and cousin). It
      is concluded that genetic study should be done if possible in all the cases of
      suspected FA, including siblings, parents and close blood relatives. It will help
      us to plan appropriate treatment and also to select suitable donor for
      hematopoietic stem cell transplantation and to plan for genetic counseling. In
      addition to the case report, the main focus of this manuscript was to review
      literature on role of FANCA gene in FA since large number of FANCA mutations and
      polymorphisms have been identified. 

PMID- 25953250
TI  - Precepting nurse practitioner students: One medical center's efforts to improve
      the precepting process.
AB  - PURPOSE: To describe the challenges shared by schools of nursing and precepting
      institutions in meeting the clinical rotation requirements for nurse practitioner
      (NP) students. A formal process was developed to screen students and provide
      appropriate clinical placement with ongoing evaluations. Detailed description of
      a preceptor class for NPs is offered. DATA SOURCES: Single institution NP survey,
      preceptor class participant survey, author experience, and PubMed, CINAHL.
      CONCLUSIONS: The barriers to precepting are well known, particularly from the
      viewpoint of schools of nursing. This article describes the barriers from a
      precepting institution's standpoint. Standardizing processes and expectations for
      NP students and preceptors improves the overall efficiency, effectiveness, and
      safety of the clinical experiences. IMPLICATIONS FOR PRACTICE: Highlights of an
      NP preceptor class and efforts to streamline precepting arrangements are
      described. Lessons learned, including the need to minimize paperwork burden on
      students during the preclinical period and the continued need for improvement of
      evaluation tools, are discussed. Recommendations for ways to blend specialty
      rotations with primary care rotations are made.

PMID- 25953251
TI  - Programmed cell death in seeds of angiosperms.
AB  - During the diversification of angiosperms, seeds have evolved structural,
      chemical, molecular and physiologically developing changes that specially affect
      the nucellus and endosperm. All through seed evolution, programmed cell death
      (PCD) has played a fundamental role. However, examples of PCD during seed
      development are limited. The present review examines PCD in integuments,
      nucellus, suspensor and endosperm in those representative examples of seeds
      studied to date. 

PMID- 25953252
TI  - Ultrasound's 'window on the womb' brings ethical challenges for balancing
      maternal and fetal health interests: obstetricians' experiences in Australia.
AB  - BACKGROUND: Obstetric ultrasound has become a significant tool in obstetric
      practice, however, it has been argued that its increasing use may have adverse
      implications for women's reproductive freedom. This study aimed to explore
      Australian obstetricians' experiences and views of the use of obstetric
      ultrasound both in relation to clinical management of complicated pregnancy, and
      in situations where maternal and fetal health interests conflict. METHODS: A
      qualitative study was undertaken as part of the CROss-Country Ultrasound Study
      (CROCUS). Interviews were held in November 2012 with 14 obstetricians working in
      obstetric care in Victoria, Australia. Data were analysed using qualitative
      content analysis. RESULTS: One overall theme emerged from the analyses: The
      ethical challenge of balancing maternal and fetal health interests, built on four
      categories: First, Encountering maternal altruism' described how pregnant women's
      often 'altruistic' position in relation to the health and wellbeing of the fetus
      could create ethical challenges in obstetric management, particularly with an
      increasing imbalance between fetal benefits and maternal harms. Second, 'Facing
      shifting attitudes due to visualisation and medico-technical advances'
      illuminated views that ultrasound and other advances in care have contributed to
      a shift in what weight to give maternal versus fetal welfare, with increasing
      attention directed to the fetus. Third, 'Guiding expectant parents in decision
      making' described the difficult task of facilitating informed decision-making in
      situations where maternal and fetal health interests were not aligned, or in
      situations characterised by uncertainty. Fourth, 'Separating private from
      professional views' illuminated divergent views on when the fetus can be regarded
      as a person. The narratives indicated that the fetus acquired more consideration
      in decision-making the further the gestation progressed. However, there was
      universal agreement that obstetricians could never act on fetal grounds without
      the pregnant woman's consent. CONCLUSIONS: This study suggests that medico
      technical advances such as ultrasound have set the scene for increasing ethical
      dilemmas in obstetric practice. The obstetricians interviewed had experienced a
      shift in previously accepted views about what weight to give maternal versus
      fetal welfare. As fetal diagnostics and treatment continue to advance, how best
      to protect pregnant women's right to autonomy requires careful consideration and
      further investigation.

PMID- 25953253
TI  - Effect of Nocturnal Intermittent Hypoxia on Left Atrial Appendage Flow Velocity
      in Atrial Fibrillation.
AB  - BACKGROUND: The mechanism underlying the associations of sleep-disordered
      breathing (SDB) with stroke and atrial fibrillation (AF) is not well established.
      We explored the relationship between nocturnal intermittent hypoxia, a marker of
      SDB, and left atrial (LA)/LA appendage (LAA) function among AF patients. METHODS:
      We evaluated 134 consecutive AF candidates for catheter ablation (age, 59.6 +/-
      9.4 years; body mass index [BMI], 24.8 +/- 3.2; Congestive Heart Failure,
      Hypertension, Age (>=75 years), Diabetes, Stroke/Transient Ischemic Attack,
      Vascular Disease, Age (65-74 years), Sex (Female) (CHA2DS2-VASc) score, 1.2 +/-
      1.1, paroxysmal AF, n = 83) using nocturnal pulse oximetry, a noninvasive
      screening method for nocturnal intermittent hypoxia. Based on 3% oxygen
      desaturation index (3% ODI), patients were divided into nocturnal intermittent
      hypoxia (3% ODI > 15; n = 32) and control groups (3% ODI <= 15; n = 102).
      RESULTS: The nocturnal intermittent hypoxia group demonstrated significantly
      higher weight, BMI, Congestive Heart Failure, Hypertension, Age, Diabetes,
      Stroke/Transient Ischemic Attack (CHADS2) and CHA2DS2-VASc scores, serum
      hemoglobin A1c and plasma brain natriuretic peptide levels, LA size, and
      prevalence of hypertension, vascular disease, and sick sinus syndrome.
      Echocardiographically, nocturnal intermittent hypoxia was associated with a
      higher grade of spontaneous echo contrast and low LAA flow velocity. Multiple
      regression analysis adjusted for type of AF, CHA2DS2-VASc score, BMI, plasma
      brain natriuretic peptide level, LA size, and rhythm on echocardiography revealed
      that 3% ODI was a factor independently associated with LAA flow velocity (beta = 
      0.184; 95% confidence interval, -0.818 to -0.006). CONCLUSIONS: Nocturnal
      intermittent hypoxia was an independent determinant for low LAA flow velocity in
      patients with AF, suggesting that the connection between SDB and LAA function
      might underlie the association of AF with stroke.

PMID- 25953254
TI  - Divergence in three newly identified Arthrospira species from Mexico.
AB  - Arthrospira (Spirulina) is a microalgae that has a unique set of biological
      characteristics which are very useful for a broad range of applications. Based on
      its worldwide requirements, this investigation was conducted to collect, isolate
      and identify the local Arthrospira strains in the central and western part of
      Mexico. We have successfully collected, isolated and identified (morphologically
      as well as molecularly) three Arthrospira strains from different regions in
      Mexico. Morphological studies were conducted by analyzing the size and shape of
      the helix, the spiral pattern, cell length and width with the help of light
      microscopy and for molecular analysis, the 16S rRNA and internally transcribed
      spacer (ITS, 16S-23 rRNA) gene partial sequence were used followed by
      phylogenetic analysis. The three species were completely different in their
      filament size and width whereas their ITS sequences were the same in size and
      more than 87 % similar in nucleotide sequence. The resulted morphological and
      phylogenetic analysis concluded that the three stains were identified as
      Arthrospira platensis. Inspite of their morphological variations and differences
      they were grouped genetically into one cluster along with the A. platensis of
      reported strains of Gene Bank database (NCBI). One of the isolated strains NPS-0,
      is probably the biggest Arthrospira strains ever reported and can be suitable for
      industrial scale biomass and protein production.

PMID- 25953256
TI  - Effect of myofilament Ca(2+) sensitivity on Ca(2+) wave propagation in rat
      ventricular muscle.
AB  - BACKGROUND: The propagation velocity of Ca(2+) waves determines delayed
      afterdepolarization and affects the occurrence of triggered arrhythmias in
      cardiac muscle. We focused on myofilament Ca(2+) sensitivity, investigating how
      the velocity of Ca(2+) waves responds to its increased sensitivity resulting from
      muscle stretch or the addition of a myofilament Ca(2+) sensitizer, SCH00013. We
      further investigated whether production of reactive oxygen species (ROS) may be
      involved in the change in velocity. METHODS: Trabeculae were obtained from rat
      hearts. Force, sarcomere length, and [Ca(2+)]i were measured. ROS production was
      estimated from 2',7'-dichlorofluorescein (DCF) fluorescence. Trabeculae were
      exposed to a 10 mM Ca(2+) jet for the induction of Ca(2+) leak from the
      sarcoplasmic reticulum in its exposed region. Ca(2+) waves were induced by 2.5-Hz
      stimulus trains for 7.5s (24  degrees C, 2.0 mM [Ca(2+)]o). Muscle stretch of 5,
      10, and 15% was applied 300 ms after the last stimulus of the train. RESULTS:
      Muscle stretch increased the DCF fluorescence, the amplitude of
      aftercontractions, and the velocity of Ca(2+) waves depending on the degree of
      stretch. After preincubation with 3 MUM diphenyleneiodonium (DPI), muscle stretch
      increased only the amplitude of aftercontractions but not the DCF fluorescence
      nor the velocity of Ca(2+) waves. SCH00013 (30 MUM) increased the DCF
      fluorescence, the amplitude of aftercontractions, and the velocity of Ca(2+)
      waves. DPI suppressed these increases. CONCLUSIONS: Muscle stretch increases the
      velocity of Ca(2+) waves by increasing ROS production, not by increasing
      myofilament Ca(2+) sensitivity. In the case of SCH00013, ROS production increases
      myofilament Ca(2+) sensitivity and the velocity of Ca(2+) waves. These results
      suggest that ROS rather than myofilament Ca(2+) sensitivity plays an important
      role in the determination of the velocity of Ca(2+) waves, that is,
      arrhythmogenesis.

PMID- 25953255
TI  - Combination of eccentric exercise and neuromuscular electrical stimulation to
      improve biomechanical limb symmetry after anterior cruciate ligament
      reconstruction.
AB  - BACKGROUND: We have previously reported that an eccentrically-based
      rehabilitation protocol post-ACLr induced greater quadriceps activation and
      strength than a neuromuscular electrical stimulation (NMES) intervention and was
      just as effective as a combined NMES and eccentric intervention. However, the
      effect an eccentrically-based intervention has on restoring normal knee mechanics
      during a single-legged landing task remains unknown. METHODS: Thirty-six
      individuals post-injury were placed into four treatment groups: NMES and
      eccentrics, eccentrics-only, NMES-only, standard of care, and healthy controls
      participated. NMES and eccentrics received a combined NMES and eccentric protocol
      post-reconstruction (each treatment 2* per week for 6 weeks), whereas groups NMES
      only and eccentric-only received only the NMES or eccentric therapy,
      respectively. To evaluate knee mechanics limb symmetry, the area under the curve
      for knee flexion angle and extension moment was derived and then normalized to
      the contralateral limb. Quadriceps strength was evaluated using the quadriceps
      index. FINDINGS: Compared to healthy, reduced sagittal plane knee limb symmetry
      was found for groups NMES-only, ECC-only and standard of care for knee extension
      moment (P<0.05). No difference was detected between healthy and NMES and
      eccentrics (P>0.06). No difference between groups was detected for knee flexion
      angle limb symmetry (P>0.05). Greater knee flexion angles and moments over stance
      were related to quadriceps strength. INTERPRETATION: The NMES and eccentrics
      group was found to restore biomechanical limb symmetry that was most closely
      related to healthy individuals following ACL reconstruction. Greater knee flexion
      angles and moments over stance were related to quadriceps strength.

PMID- 25953257
TI  - Obesity induced by high fat diet attenuates postinfarct myocardial remodeling and
      dysfunction in adult B6D2F1 mice.
AB  - Obesity is a major risk factor for cardiovascular morbidity and mortality.
      However, some studies suggest that among patients with established cardiovascular
      disease, obesity is associated with better prognosis, a phenomenon described as
      the obesity paradox. In this study we tested the hypothesis that obesity with
      hyperinsulinemia and without hyperglycemia attenuates the impact of transient
      coronary occlusion on left ventricular remodeling and function. B6D2F1 mice from
      both genders fed with a high fat diet (HFD) or control diet for 6 months were
      subjected to 45 min of coronary occlusion and 28 days of reperfusion. Left
      ventricular dimensions and function were assessed by serial echocardiography, and
      infarct size was determined by Picrosirius red staining. HFD mice developed
      obesity with hypercholesterolemia and hyperinsulinemia in the absence of
      hyperglycemia or hypertension. During the period of feeding, no changes were
      observed in ventricular mass, volume or function, or in vascular reactivity. HFD
      attenuated the consequences of transient coronary occlusion as shown by a marked
      reduction in infarct size (51%, P = 0.021) and cardiac dilation, as well as
      improved left ventricular function as compared to control diet animals. These
      effects were associated with enhanced reperfusion injury salvage kinases (RISK)
      pathway function in HFD hearts shown as increased Akt and GSK3beta
      phosphorylation. These results demonstrate that dietary obesity without
      hyperglycemia or hypertension attenuates the impact of ischemia/reperfusion
      injury in association with increased insulin signaling and RISK activation. This
      study provides experimental support to the controversial concept of the obesity
      paradox in humans.

PMID- 25953258
TI  - T-tubule disease: Relationship between t-tubule organization and regional
      contractile performance in human dilated cardiomyopathy.
AB  - Evidence from animal models suggest that t-tubule changes may play an important
      role in the contractile deficit associated with heart failure. However samples
      are usually taken at random with no regard as to regional variability present in
      failing hearts which leads to uncertainty in the relationship between contractile
      performance and possible t-tubule derangement. Regional contraction in human
      hearts was measured by tagged cine MRI and model fitting. At transplant, failing
      hearts were biopsy sampled in identified regions and immunocytochemistry was used
      to label t-tubules and sarcomeric z-lines. Computer image analysis was used to
      assess 5 different unbiased measures of t-tubule structure/organization. In
      regions of failing hearts that showed good contractile performance, t-tubule
      organization was similar to that seen in normal hearts, with worsening structure
      correlating with the loss of regional contractile performance. Statistical
      analysis showed that t-tubule direction was most highly correlated with local
      contractile performance, followed by the amplitude of the sarcomeric peak in the
      Fourier transform of the t-tubule image. Other area based measures were less well
      correlated. We conclude that regional contractile performance in failing human
      hearts is strongly correlated with the local t-tubule organization. Cluster tree
      analysis with a functional definition of failing contraction strength allowed a
      pathological definition of 't-tubule disease'. The regional variability in
      contractile performance and cellular structure is a confounding issue for
      analysis of samples taken from failing human hearts, although this may be
      overcome with regional analysis by using tagged cMRI and biopsy mapping. 

PMID- 25953259
TI  - Predictive factors for oral intake after aspiration pneumonia in older adults.
AB  - AIM: The purpose of the present study was to clarify the predictive factors for
      achieving oral intake after aspiration pneumonia in elderly patients. METHODS:
      This retrospective observational study used data from the Japanese Diagnosis
      Procedure Combination inpatient database. We identified patients who were
      admitted to acute-care hospitals with aspiration pneumonia. The outcome was time
      to achieve total oral intake. We carried out Cox regression analysis to identify
      predictors for the early initiation of total oral intake. RESULTS: Of 66 611
      elderly patients with aspiration pneumonia, 59% achieved total oral intake within
      30 days. Cox regression analysis showed that early initiation of total oral
      intake was associated with female sex and higher Barthel Index. Delayed
      initiation of total oral intake was associated with underweight, higher scores of
      pneumonia severity and comorbidities. CONCLUSION: We clarified prognostic factors
      for total oral intake in elderly aspiration pneumonia patients. Our findings will
      be helpful in nutritional care planning for elderly aspiration pneumonia
      patients. Geriatr Gerontol Int 2016; 16: 556-560.

PMID- 25953260
TI  - Downregulation of miR-22 acts as an unfavorable prognostic biomarker in
      osteosarcoma.
AB  - miRNA-22 (miR-22) has been showed to involve in a variety of cancers; however,
      the association between miR-22 expression level and the prognosis of osteosarcoma
      is also poorly unknown. Fifty-two patients with surgically resected paired
      osteosarcoma and non-neoplastic disease between 2008 and 2014 were involved in
      this study. Real-time PCR was performed to examine the expression level of miR-22
      in osteosarcoma tissues and noncancerous bone tissues. Then the association
      between miR-22 expression and clinical-pathological parameters were further
      evaluated. Kaplan-Meier analysis and Cox proportional hazards regression models
      were explored to reveal the correlations of miR-22 expression with survival of
      patients. The results indicated that miR-22 was downregulated in osteosarcoma
      tissues in comparison with noncancerous bone tissues. In addition, there is
      statistically significance between miR-22 expression level and recurrence,
      metastasis, and chemotherapy response. The patients with lower miR-22 expression
      level had both poorer overall survival and disease-free survival. The
      multivariant analysis revealed that the miR-22 expression level and metastasis
      status are independent prognosis factors for osteosarcoma. In conclusion, miR-22
      was downregulated in osteosarcoma and its expression level was correlated with a
      variety of important clinical-pathological parameters. Moreover, miR-22 may serve
      as a promising biomarker for predicting the prognosis of osteosarcoma.

PMID- 25953261
TI  - A novel biomarker C6orf106 promotes the malignant progression of breast cancer.
AB  - C6orf106 (chromosome 6 open reading frame 106) is a recently discovered protein
      encoded by the 6th chromosome. Though many proteins encoded by chromosome 6 are
      reportedly related to cancer, schizophrenia, autoimmunity and many other
      diseases, the function of C6orf106 was not well demonstrated so far. As measured
      by immunohistochemical staining, C6orf106 was positive in normal breast duct
      myoepithelial cells (92.31 %, 72/78), but negative in normal breast duct
      glandular epithelial cells (3.85 %, 3/78). In breast ductal carcinoma in situ,
      C6orf106 showed weakly or moderately positive (77.97 %, 46/59), but it was
      significantly strongly positive in invasive ductal carcinoma (79.57 %, 148/186).
      The expression intensity of C6orf106 seemed increased significantly along with
      the malignancy of breast cancer (p < 0.001). Additionally, C6orf106 expression
      was significantly correlated with TNM stage (p = 0.001 and p = 0.004) and lymph
      node metastasis (p = 0.018 and p = 0.025) of the overall and the triple-negative
      breast cancer, respectively. Consistently, we found that the interference of
      C6orf106 was able to inhibit cell proliferation and invasion of two triple
      negative breast cancer cell lines, MDA-MB-231 and BT-549, accompanied by the
      decrease of cyclin A2, cyclin B1, c-myc, and N-cadherin and the increase of E
      cadherin. Collectively, these results indicate that C6orf106 may promote tumor
      progression in the invasive breast cancer, particularly in triple-negative breast
      cancer, and C6orf106 might serve as a novel therapeutic target of breast cancer,
      especially for triple-negative breast cancer.

PMID- 25953262
TI  - Differential regulation and function of tumor-infiltrating T cells in different
      stages of breast cancer patients.
AB  - Breast cancer survival was associated with higher frequencies of CD8(+) T
      cytotoxic T cells in infiltrating lymphocytes. On the other hand, the frequency
      of CD4(+)CD25(+)FoxP3(+) regulatory T cells was inversely correlated with
      clinical outcomes of breast cancer. The regulation and interaction of different
      types of tumor-infiltrating T cells in different stages of breast cancer patients
      are still unclear. In this study, we examined the functions and regulations of
      CD8(+) T cells and CD4(+)CD25(+)FoxP3(+) T cells from resected tumors from 12
      stage I, 24 stage II, and 20 stage III untreated breast cancer patients. We found
      that tumor-infiltrating CD8(+) T cells from stage III patients were more
      refractory to T cell receptor (TCR) stimulation than those from stage I and stage
      II patients in terms of interferon gamma (IFN-gamma) production and
      proliferation. On the other hand, tumor-infiltrating CD4(+)CD25(+)FoxP3(+) T
      cells had higher proliferation in stage III tumors than in stage I and stage II
      tumors. In addition, we found that tumor-infiltrating CD4(+)CD25(+) T cells can
      suppress CD8(+) T cell inflammation ex vivo. Altogether, our data demonstrated
      that stage III tumors in breast cancer patients had a more immunosuppressive
      microenvironment.

PMID- 25953263
TI  - Revealing genome-wide mRNA and microRNA expression patterns in leukemic cells
      highlighted "hsa-miR-2278" as a tumor suppressor for regain of chemotherapeutic
      imatinib response due to targeting STAT5A.
AB  - BCR-ABL oncoprotein stimulates cell proliferation and inhibits apoptosis in
      chronic myeloid leukemia (CML). For cure, imatinib is a widely used tyrosine
      kinase inhibitor, but developing chemotherapeutic resistance has to be overcome.
      In this study, we aimed to determine differing genome-wide microRNA (miRNA) and
      messenger RNA (mRNA) expression profiles in imatinib resistant (K562/IMA-3 MUM)
      and parental cells by targeting STAT5A via small interfering RNA (siRNA)
      applications. After determining possible therapeutic miRNAs, we aimed to check
      their effects upon cell viability and proliferation, apoptosis, and find a
      possible miRNA::mRNA interaction to discover the molecular basis of imatinib
      resistance. We detected that miR-2278 and miR-1245b-3p were most significantly
      regulated miRNAs according to miRNome array. Upregulating miR-2278 expression
      resulted in the inhibition of resistant leukemic cell proliferation and induced
      apoptosis, whereas miR-1245b-3p did not exhibit therapeutic results. Functional
      analyses indicated that AKT2, STAM2, and STAT5A mRNAs were functional targets for
      miR-2278 as mimic transfection decreased their expressions both at
      transcriptional and translational level, thus highlighting miR-2278 as a tumor
      suppressor. This study provides new insights in discovering the mechanism of
      imatinib resistance due to upregulating the tumor-suppressor hsa-miR-2278 which
      stands for a functional therapeutic approach, inhibited leukemic cell
      proliferation, induced apoptosis, and regain of chemotherapeutic drug response in
      CML therapy.

PMID- 25953265
TI  - Preoperative serum markers for individual patient prognosis in stage I-III colon
      cancer.
AB  - Carcinoembryonic antigen (CEA) remains the only recommended biomarker for follow
      up care of colorectal cancer (CRC), but besides CEA, several other serological
      parameters have been proposed as prognostic markers for CRC. The present
      retrospective analysis investigates a comprehensive set of serum markers with
      regard to cancer-specific survival (CSS) and disease-free survival (DFS). A total
      of 472 patients with colon cancer underwent surgery for curative intent between
      January 1988 and June 2007. Preoperative serum was analyzed for the following
      parameters: albumin, alkaline phosphatase (aP), beta-human chorionic gonadotropin
      (betahCG), bilirubin, cancer antigen 125 (CA 125), cancer antigen 19-9 (CA 19-9),
      CA 72-4, CEA, C-reactive protein (CRP), cytokeratin-19 soluble fragment (CYFRA 21
      1), ferritin, gamma-glutamyltransferase (gammaGT), glutamate oxaloacetate
      transaminase (GOT), glutamate pyruvate transaminase (GPT), hemoglobin,
      haptoglobin, interleukin-6, interleukin-8, creatinine, lactate dehydrogenase
      (LDH), serum amyloid A (SAA), and 25-hydroxyvitamin D. After a median follow-up
      period of 5.9 years, the overall 3- and 5-year CSS was 91.7 and 84.9 % and DFS
      rates were 82.7 % (3 years) and 77.6 % (5 years). Multivariate analyses confirmed
      preoperative CEA as an independent prognostic factor with regard to CSS and DFS.
      CA 19-9 and gammaGT also provided prognostic value for CSS and DFS, respectively.
      Younger age was negatively associated with DFS. According to UICC stage, CEA
      provided significant prognostic value with regard to CSS and DFS, while CA 19-9
      was only prognostic for CSS. Combined analysis is able to identify patients with
      favorable prognosis. In addition to tumor baseline parameters, preoperative CEA
      could be confirmed as prognostic marker in colon cancer. CA 19-9 and gammaGT also
      provide additional prognostic value with regard to survival and recurrence in
      stage III and stage I disease, respectively. The combined use of CEA together
      with CA 19-9 and gammaGT improve risk-adapted post-op surveillance.

PMID- 25953264
TI  - Expression profiling of cancer-related galectins in acute myeloid leukemia.
AB  - Acute myeloid leukemia (AML) is the most common type of leukemia in adults with
      the lowest survival rate of all the leukemias. It is a heterogeneous disease in
      which a variety of cytogenetic and molecular alterations have been identified.
      Some galectins were previously reported to have important roles in cancer-like
      neoplastic transformation, tumor cell survival, angiogenesis, and tumor
      metastasis. Previous studies have showed that some galectin family members play a
      role in various types of leukemia. The present study aims at evaluating and
      clarifying the diagnostic and prognostic value of the expression of cancer
      related galectins in relation to the clinicopathological characters of AML
      patients. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to
      detect expression profile of eight galectin family members (galectin-1, -2, -3, 
      4, -8, -9, -12, and -13) in 53 newly diagnosed de novo AML patients. The samples
      were collected from the inpatient clinic at National Cancer Institute (NCI),
      Cairo University (CU), diagnosed between July 2012 and May 2013. Our results show
      that patients with lower LGALS12 gene expression have a lower overall survival
      than those with higher expression (P value <0.026). Moreover, a statistically
      significant association between the LGALS4 gene expression and patient age is
      found. Hence, the higher expression of LGALS4 gene is associated with younger age
      (adjusted P value <0.001). In conclusion, galectin-12 may be a potential
      prognostic marker for AML.

PMID- 25953266
TI  - Sesquiterpene lactones derived from Saussurea lappa induce apoptosis and inhibit
      invasion and migration in neuroblastoma cells.
AB  - Neuroblastoma is among the most fatal of solid tumors in the pediatric age group,
      even when treated aggressively. Therefore, a new effective therapeutic drug(s)
      for neuroblastoma is urgently needed. To clarify the anticancer effects of the
      sesquiterpene lactones dehydrocostus lactone and costunolide, derived from
      Saussurea lappa, we examined the cytotoxic and migration/invasion-inhibitory
      effects of these compounds against neuroblastoma cell lines. Both the compounds
      exerted significant cytotoxicity against the neuroblastoma cell lines IMR-32, NB
      39, SK-N-SH, and LA-N-1. Evidence of cellular apoptosis, such as nuclear
      condensation and membrane inversion, were observed after treatment with these
      compounds. Both compounds induced caspase-7 activation and PARP cleavage as
      confirmed by Western blotting. Furthermore, the sesquiterpene lactones also
      suppressed invasion and migration of the neuroblastoma cells. These results
      suggest that dehydrocostus lactone and costunolide are promising candidates for
      being developed into novel anticancer drugs effective against neuroblastoma. 

PMID- 25953267
TI  - The potent activation of Ca(2+)-activated K(+) current by NVP-AUY922 in the human
      pancreatic duct cell line (PANC-1) possibly independent of heat shock protein 90
      inhibition.
AB  - NVP-AUY922 (AUY) is a potent inhibitor of heat shock protein 90 (HSP90). Whether
      this compound can exert additional effects on membrane ion channels remains
      elusive. We investigated the effect of AUY on ion currents in human pancreatic
      duct epithelial cells (PDECs), including PANC-1 and MIA PaCa-2. AUY increased the
      amplitude of the K(+) current (IK) in PANC-1 cells shown by whole-cell
      configuration. Single-channel recordings revealed a large-conductance Ca(2+)
      activated K(+) (BKCa) channel in PANC-1, but not in MIA PaCa-2. In cell-attached
      mode, AUY increased the probability of BKCa channel opening and also potentiated
      the activity of stretch-induced channels. However, other HSP inhibitors, 17-AAG
      or BIIB021 only slightly increased the activity of BKCa channels. In inside-out
      recordings, sodium hydrosulphide or caffeic acid phenethyl ester increased the
      activity of BKCa channels, but AUY did not. We further evaluated whether
      conductance of Ca(2+)-activated K(+) channels (IK(Ca)) influenced secretion of
      HCO3(-) and fluid in PDECs by using a modified Whitcomb-Ermentrout model.
      Simulation studies showed that an increase in IK(Ca) resulted in additional
      secretion of HCO3(-) and fluid by mimicking the effect of AUY in PDECs.
      Collectively, AUY can interact with the BKCa channel to largely increase IK(Ca)
      in PDECs. 

PMID- 25953268
TI  - Induction of CYP3A by morroniside in rats.
AB  - Morroniside is one of the most important iridoid glycosides in the herbal drug
      Cornus officinalis Sieb. et Zucc. The current study was designed to investigate
      the ex vivo and in vivo effects of morroniside on CYP3A activity in rats after
      treatment with morroniside for 7 days (at 10, 30, 90 mg/kg, i.g.). Morroniside
      was found to induce CYP3A. According to the ex vivo experiment, the activity of
      CYP3A was measured by the quantification of 1-hydroxymidazolam, which was the
      metabolite from CYP3A probe substrate, midazolam. The concentration of 1
      hydroxymidazolam was determined by using a validated liquid chromatography
      coupled with tandem mass spectrometry detection (LC-MS/MS) method. The levels of
      messenger RNA (mRNA) and protein of CYP3A were determined by reverse
      transcriptase-polymerase chain reaction (RT-PCR) and western blotting analysis,
      respectively. The pharmacokinetics of midazolam in rats after treatment with
      morroniside for 7 days (at 10, 30, 90 mg/kg, i.g.) were investigated in vivo.
      After treatment with morroniside, the activity, mRNA and protein expression of
      CYP3A were significantly induced and the absorbance and bioavailability of
      midazolam in rats were reduced. The results indicated that morroniside could
      induce the activity of CYP3A. 

PMID- 25953269
TI  - L-Citrulline dilates rat retinal arterioles via nitric oxide- and prostaglandin
      dependent pathways in vivo.
AB  - L-Citrulline is an effective precursor of L-arginine produced by the L
      citrulline/L-arginine cycle, and it exerts beneficial effects on the
      cardiovascular system by supporting enhanced nitric oxide (NO) production. NO
      dilates retinal blood vessels via the cyclooxygenase-mediated pathway. The
      purpose of this study was to examine the effects of L-citrulline on retinal
      circulation and to investigate the potential involvement of NO and prostaglandins
      in L-citrulline-induced responses in rats. L-Citrulline (10-300 MUg kg(-1) min(
      1), i.v.) increased the diameter of retinal arterioles without significantly
      changing mean blood pressure, heart rate, and fundus blood flow. The vasodilator
      response of retinal arterioles to l-citrulline was significantly diminished
      following treatment with N(G)-nitro-L-arginine methyl ester (30 mg/kg, i.v.), an
      NO synthase inhibitor, or indomethacin (5 mg/kg, i.v.), a cyclooxygenase
      inhibitor. In addition, alpha-methyl-dl-aspartic acid (147 mg/kg, i.v.), an
      inhibitor of argininosuccinate synthase, the rate-limiting enzyme for the
      recycling of l-citrulline to l-arginine, diminished the L-citrulline-induced
      retinal vasodilation. These results suggest that both NO- and prostaglandin
      dependent pathways contribute to the L-citrulline-induced vasodilation of rat
      retinal arterioles. The L-citrulline/L-arginine recycling pathway may have more
      importance in regulating vascular tone in retinal blood vessels than in
      peripheral resistance vessels.

PMID- 25953271
TI  - Human case of Onchocerca lupi infection, Germany, August 2014.
AB  - Onchocerca lupi, a nematode parasite infecting dogs and cats with a hitherto
      unknown arthropod vector, is also being recognised as a parasite also responsible
      for human eye infections. Here we describe a case of human eye infection
      diagnosed molecularly by nematode 12S rDNA PCR in a German patient who had
      travelled to Tunisia and Turkey. The patient recovered after treatment with
      antibiotic and anti-inflammatory therapy.

PMID- 25953270
TI  - High-fat diet enhanced retinal dehydrogenase activity, but suppressed retinol
      dehydrogenase activity in liver of rats.
AB  - Evidence has shown that hyperlipidemia is associated with retinoid
      dyshomeostasis. In liver, retinol is mainly oxidized to retinal by retinol
      dehydrogenases (RDHs) and alcohol dehydrogenases (ADHs), further converted to
      retinoic acid by retinal dehydrogenases (RALDHs). The aim of this study was to
      investigate whether high-fat diet (HFD) induced hyperlipidemia affected activity
      and expression of hepatic ADHs/RDHs and RALDHs in rats. Results showed that
      retinol levels in liver, kidney and adipose tissue of HFD rats were significantly
      increased, while plasma retinol and hepatic retinal levels were markedly
      decreased. HFD rats exhibited significantly downregulated hepatic ADHs/RDHs
      activity and Adh1, Rdh10 and Dhrs9 expression. Oppositely, hepatic RALDHs
      activity and Raldh1 expression were upregulated in HFD rats. In HepG2 cells,
      treatment of HFD rat serum inhibited ADHs/RDHs activity and induced RALDHs
      activity. Among the tested abnormally altered components in HFD rat serum,
      cholesterol reduced ADHs/RDHs activity and RDH10 expression, while induced RALDHs
      activity and RALDH1 expression in HepG2 cells. Contrary to the effect of
      cholesterol, cholesterol-lowering agent pravastatin upregulated ADHs/RDHs
      activity and RDH10 expression, while suppressed RALDHs activity and RALDH1
      expression. In conclusion, hyperlipidemia oppositely altered activity and
      expression of hepatic ADHs/RDHs and RALDHs, which is partially due to the
      elevated cholesterol levels. 

PMID- 25953272
TI  - Congenital rubella still a public health problem in Italy: analysis of national
      surveillance data from 2005 to 2013.
AB  - In accordance with the goal of the World Health Organization Regional Office for
      Europe, the Italian national measles and rubella elimination plan aims to reduce
      the incidence of congenital rubella cases to less than one case per 100,000 live
      births by the end of 2015. We report national surveillance data for congenital
      rubella and rubella in pregnancy from 2005 to 2013. A total of 75 congenital
      rubella infections were reported; the national annual mean incidence was
      1.5/100,000 live births, including probable and confirmed cases according to
      European Union case definition. Two peaks occurred in 2008 and 2012 (5.0 and
      3.6/100,000 respectively). Overall, 160 rubella infections in pregnancy were
      reported; 69/148 women were multiparous and 38/126 had had a rubella antibody
      test before pregnancy. Among reported cases, there were 62 infected newborns, 31
      voluntary abortions, one stillbirth and one spontaneous abortion. A total of 24
      newborns were unclassified and 14 women were lost to follow-up, so
      underestimation is likely. To improve follow-up of cases, systematic procedures
      for monitoring infected mothers and children were introduced in 2013. To prevent
      congenital rubella, antibody screening before pregnancy and vaccination of
      susceptible women, including post-partum and post-abortum vaccination, should be
      promoted. Population coverage of two doses of measles-mumps-rubella vaccination
      of >= 95% should be maintained and knowledge of health professionals improved.

PMID- 25953273
TI  - A multi-country Salmonella Enteritidis phage type 14b outbreak associated with
      eggs from a German producer: 'near real-time' application of whole genome
      sequencing and food chain investigations, United Kingdom, May to September 2014.
AB  - We report an outbreak of Salmonella Enteritidis phage type 14b (PT14b) in the
      United Kingdom (UK) between May and September 2014 where Public Health England
      launched an investigation to identify the source of infection and implement
      control measures. During the same period, outbreaks caused by a Salmonella
      Enteritidis strain with a specific multilocus variable-number tandem repeat
      analysis (MLVA) profile occurred in other European Union Member States. Isolates
      from a number of persons affected by the UK outbreak, who had initially been
      tested by MLVA also shared this particular profile. Cases were defined as any
      person infected with S. Enteritidis PT14b, resident in England or Wales and
      without history of travel outside of this geographical area during the incubation
      period, reported from 1 June 2014 onwards, with a MLVA profile of 2-11-9-7-4-3-2
      8-9 or a single locus variant thereof. In total, 287 cases met the definition.
      Food traceback investigations in the UK and other affected European countries
      linked the outbreaks to chicken eggs from a German company. We undertook whole
      genome sequencing of isolates from UK and European cases, implicated UK premises,
      and German eggs: isolates were highly similar. Combined with food traceback
      information, this confirmed that the UK outbreak was also linked to a German
      producer.

PMID- 25953274
TI  - Changing hepatitis A epidemiology in the European Union: new challenges and
      opportunities.
AB  - This perspective on hepatitis A in the European Union and European Economic Area
      (EU/EEA) presents epidemiological data on new cases and outbreaks and vaccination
      policies. Hepatitis A endemicity in the EU/EEA ranges from very low to
      intermediate with a decline in notification rates in recent decades. Vaccination
      uptake has been insufficient to compensate for the increasing number of
      susceptible individuals. Large outbreaks occur. Travel increases the probability
      of introducing the virus into susceptible populations and secondary transmission.
      Travel medicine services and healthcare providers should be more effective in
      educating travellers and travel agents regarding the risk of travel-associated
      hepatitis A. The European Centre for Disease Prevention and Control (ECDC)
      endorses the World Health Organization's recommendations on vaccination of high
      risk groups in countries with low and very low endemicity and on universal
      vaccination in countries with intermediate endemicity. Those recommendations do
      not cover the use of hepatitis A vaccine to control outbreaks. ECDC together with
      EU/EEA countries should produce evidence-based recommendations on hepatitis A
      immunisation to control outbreaks. Data about risk behaviours, exposure and
      mortality are scarce at the EU/EEA level. EU/EEA countries should report to ECDC
      comprehensive epidemiological and microbiological data to identify opportunities
      for prevention.

PMID- 25953275
TI  - Strengths and limitations of assessing influenza vaccine effectiveness using
      routinely collected, passive surveillance data in Ontario, Canada, 2007 to 2012:
      balancing efficiency versus quality.
AB  - Prompt evaluation of annual influenza vaccine effectiveness (IVE) is important.
      IVE is estimated in Ontario using a test-negative design (TND) within a national
      sentinel surveillance network (SPSN). To explore alternative approaches, we
      applied the screening method (SM) during five seasons spanning 2007 to 2012 to
      passive surveillance data to determine whether routinely collected data could
      provide unbiased IVE estimates. Age-adjusted SM-IVE estimates, excluding 2008/09
      pandemic cases and cases with missing immunisation status, were compared with TND
      IVE estimates in SPSN participants, adjusted for age, comorbidity, week of
      illness onset and interval to specimen collection. In four seasons, including the
      2009 pandemic, the SM underestimated IVE (22-39% seasonal; 72% pandemic) by 20 to
      35% relative to the TND-IVE (58-63% seasonal; 93% pandemic), except for the
      2010/11 season when both estimates were low (33% and 30%, respectively). Half of
      the cases in the routine surveillance data lacked immunisation information;
      imputing all to be unimmunised better aligned SM-IVE with TND-IVE, instead
      overestimating in four seasons by 4 to 29%. While the SM approach applied to
      routine data may offer the advantage of timeliness, ease and efficiency,
      methodological issues related to completeness of vaccine information and/or case
      ascertainment may constitute trade-offs in reliability.

PMID- 25953276
TI  - European Immunization Week 2015: 10th anniversary.

PMID- 25953277
TI  - Simultaneous extraction and quantification of lamotrigine, phenobarbital, and
      phenytoin in human plasma and urine samples using solidified floating organic
      drop microextraction and high-performance liquid chromatography.
AB  - A novel and simple method based on solidified floating organic drop
      microextraction followed by high-performance liquid chromatography with
      ultraviolet detection has been developed for simultaneous preconcentration and
      determination of phenobarbital, lamotrigine, and phenytoin in human plasma and
      urine samples. Factors affecting microextraction efficiency such as the type and
      volume of the extraction solvent, sample pH, extraction time, stirring rate,
      extraction temperature, ionic strength, and sample volume were optimized. Under
      the optimum conditions (i.e. extraction solvent, 1-undecanol (40 MUL); sample pH,
      8.0; temperature, 25 degrees C; stirring rate, 500 rpm; sample volume, 7 mL;
      potassium chloride concentration, 5% and extraction time, 50 min), the limits of
      detection for phenobarbital, lamotrigine, and phenytoin were 1.0, 0.1, and 0.3
      MUg/L, respectively. Also, the calibration curves for phenobarbital, lamotrigine,
      and phenytoin were linear in the concentration range of 2.0-300.0, 0.3-200.0, and
      1.0-200.0 MUg/L, respectively. The relative standard deviations for six replicate
      extractions and determinations of phenobarbital, lamotrigine, and phenytoin at 50
      MUg/L level were less than 4.6%. The method was successfully applied to determine
      phenobarbital, lamotrigine, and phenytoin in plasma and urine samples. 

PMID- 25953278
TI  - Job Pressure and SES-contingent Buffering: Resource Reinforcement, Substitution,
      or the Stress of Higher Status?
AB  - Analyses of the 2008 National Study of the Changing Workforce demonstrate that
      job pressure is associated with greater anxiety and job dissatisfaction. In this
      paper we ask, What conditions protect workers? The conventional buffering
      hypothesis in the Job-Demands Resource (JD-R) model predicts that job resources
      should attenuate the relationship. We test whether the conventional buffering
      hypothesis depends on socioeconomic status (SES). Support for conventional
      buffering is evident only for job dissatisfaction--and that generalizes across
      SES. When anxiety is assessed, however, we observe an SES contingency: Job
      resources attenuate the positive association between job pressure and anxiety
      among workers with lower SES, but exacerbate it among those with higher SES. We
      discuss the implications of this SES-contingent pattern for theoretical scenarios
      about "resource reinforcement," "resource substitution," and the "stress of
      higher status." Future research should consider SES indicators as potential
      contingencies in the relationship between job conditions and mental health.

PMID- 25953280
TI  - Isolated fibromuscular dysplasia of the coronary ostium: a rare cause of sudden
      death. Case report and review of the literature.
AB  - We present a unique case of sudden death in a 21-year-old man with history of
      cocaine use and a solitary fibromuscular dysplastic lesion completely occluding
      the left coronary artery ostium. We document intimal proliferation of
      myofibroblasts at the opening of the left coronary ostium without other
      concomitant lesions. This report discusses the gross and histologic features of
      the lesion, explores in careful detail the possible etiologies, and gives a
      comprehensive literature review of isolated coronary ostial fibromuscular
      dysplasia presenting with sudden death.

PMID- 25953279
TI  - An integrative model of inter- and intragenerational preconception processes
      influencing birthweight in the United States.
AB  - Social inequalities in birthweight are an important population health concern as
      low birthweight is one mechanism through which inequalities are reproduced across
      generations. Yet, we do not understand what causes these social inequalities.
      This study draws together theoretic and empiric findings from disparate
      disciplines--sociology, economics, public health, and behavior genetics--to
      develop a new integrative intra- and intergenerational model of preconception
      processes influencing birthweight. This model is empirically tested using
      structural equation modeling and population-level data containing linked mother
      daughter pairs from the National Longitudinal Survey of Youth (NLSY79) and the
      Children of the NLSY79 (N = 1,580 mother-daughter pairs). Results reveal that
      birthweight is shaped by preconception factors dating back to women's early life
      environment as well as conditions dating back three generations, via integrative
      intra- and intergenerational processes. These processes reveal specific pathways
      through which social inequality can transmit from mothers to children via
      birthweight.

PMID- 25953282
TI  - An integrative framework for the identification of double minute chromosomes
      using next generation sequencing data.
AB  - BACKGROUND: Double minute chromosomes are circular fragments of DNA whose
      presence is associated with the onset of certain cancers. Double minutes are
      lethal, as they are highly amplified and typically contain oncogenes. Locating
      double minutes can supplement the process of cancer diagnosis, and it can help to
      identify therapeutic targets. However, there is currently a dearth of
      computational methods available to identify double minutes. We propose a
      computational framework for the idenfication of double minute chromosomes using
      next-generation sequencing data. Our framework integrates predictions from
      algorithms that detect DNA copy number variants, and it also integrates
      predictions from algorithms that locate genomic structural variants. This
      information is used by a graph-based algorithm to predict the presence of double
      minute chromosomes. RESULTS: Using a previously published copy number variant
      algorithm and two structural variation prediction algorithms, we implemented our
      framework and tested it on a dataset consisting of simulated double minute
      chromosomes. Our approach uncovered double minutes with high accuracy,
      demonstrating its plausibility. CONCLUSIONS: Although we only tested the
      framework with three programs (RDXplorer, BreakDancer, Delly), it can be extended
      to incorporate results from programs that 1) detect amplified copy number and
      from programs that 2) detect genomic structural variants like deletions,
      translocations, inversions, and tandem repeats. The software that implements the
      framework can be accessed here: https://github.com/mhayes20/DMFinder

PMID- 25953283
TI  - Advanced magnetic resonance techniques: 3 T.
AB  - Magnetic resonance (MR) imaging at 3 T is clinically feasible and, in the right
      context, can provide improvements compared with 1.5-T MR imaging. Improvements in
      both signal/noise ratio and contrast/noise ratio can be used to improve image
      homogeneity and/or spatial and temporal resolution. Some techniques, such as
      brain functional MR imaging, are considered far superior at 3 T than at 1.5 T.
      Although several challenges still exist, 3 T has been become well established in
      clinical MR imaging.

PMID- 25953281
TI  - Ecological and Genetic Barriers Differentiate Natural Populations of
      Saccharomyces cerevisiae.
AB  - How populations that inhabit the same geographical area become genetically
      differentiated is not clear. To investigate this, we characterized phenotypic and
      genetic differences between two populations of Saccharomyces cerevisiae that in
      some cases inhabit the same environment but show relatively little gene flow. We
      profiled stress sensitivity in a group of vineyard isolates and a group of oak
      soil strains and found several niche-related phenotypes that distinguish the
      populations. We performed bulk-segregant mapping on two of the distinguishing
      traits: The vineyard-specific ability to grow in grape juice and oak-specific
      tolerance to the cell wall damaging drug Congo red. To implicate causal genes, we
      also performed a chemical genomic screen in the lab-strain deletion collection
      and identified many important genes that fell under quantitative trait loci
      peaks. One gene important for growth in grape juice and identified by both the
      mapping and the screen was SSU1, a sulfite-nitrite pump implicated in wine
      fermentations. The beneficial allele is generated by a known translocation that
      we reasoned may also serve as a genetic barrier. We found that the translocation
      is prevalent in vineyard strains, but absent in oak strains, and presents a
      postzygotic barrier to spore viability. Furthermore, the translocation was
      associated with a fitness cost to the rapid growth rate seen in oak-soil strains.
      Our results reveal the translocation as a dual-function locus that enforces
      ecological differentiation while producing a genetic barrier to gene flow in
      these sympatric populations. 

PMID- 25953284
TI  - Noncontrast magnetic resonance angiography: concepts and clinical applications.
AB  - Many noncontrast magnetic resonance angiography techniques have recently been
      developed in response to concerns about gadolinium in patients with renal
      impairment. This article describes the theory behind established and recently
      described techniques and how and where they can be performed in clinical
      practice. 

PMID- 25953285
TI  - Recent advances in brain and spine imaging.
AB  - Advanced MR imaging techniques have found extensive utility in the clinical
      practice of neuroradiology. A variety of these techniques are incorporated into
      imaging protocols for routine use, specific applications to particular disease
      entities, or as problem-solving tools on an ad hoc basis. This article summarizes
      and illustrates the spectrum of advanced MR imaging tools used clinically in the
      practice of neuroradiology. 

PMID- 25953286
TI  - Perfusion imaging in neuro-oncology: basic techniques and clinical applications.
AB  - Perfusion imaging is a method for assessing the flow of blood occurring at the
      tissue level and can be accomplished by both CT and MR perfusion techniques. The
      use of perfusion imaging has increased substantially in the past decade,
      particularly in neuro-oncologic imaging, where it is has been used for brain
      tumor grading and directing biopsies or targeted therapy, as well as for the
      evaluation of treatment response and disease progression. This article discusses
      the basic principles and techniques of perfusion imaging, as well as its
      applications in neuro-oncology. 

PMID- 25953287
TI  - Focus on advanced magnetic resonance techniques in clinical practice: magnetic
      resonance neurography.
AB  - Magnetic resonance neurography (MRN) provides the greatest degree of soft tissue
      contrast in the evaluation of peripheral nerves. Utilization of MRN relies on (1)
      peripheral nerve anatomy, (2) the spectrum of pathology, and (3) familiarity with
      dedicated MR imaging techniques. Although there remain several pitfalls in MRN
      imaging, awareness of these pitfalls improves imaging quality and limits
      misinterpretation. Most importantly, maintaining a direct line of communication
      with the referring clinician allows for the greatest degree of diagnostic
      accuracy. 

PMID- 25953288
TI  - Metal artifact reduction: standard and advanced magnetic resonance and computed
      tomography techniques.
AB  - An increasing number of joint replacements are being performed in the United
      States. Patients undergoing these procedures can have various complications.
      Imaging is one of the primary means of diagnosing these complications. Cross
      sectional imaging techniques, such as computed tomography (CT) and MR imaging,
      are more sensitive than radiographs for evaluating complications. The use of CT
      and MR imaging in patients with metallic implants is limited by the presence of
      artifacts. This review discusses the causes of metal artifacts on MR imaging and
      CT, contributing factors, and conventional and novel methods to reduce the
      effects of these artifacts on scans. 

PMID- 25953289
TI  - Advanced Noncontrast MR Imaging in Musculoskeletal Radiology.
AB  - Multiple nonmorphologic magnetic resonance sequences are available in
      musculoskeletal imaging that can provide additional information to better
      characterize and diagnose musculoskeletal disorders and diseases. These sequences
      include blood-oxygen-level-dependent (BOLD), arterial spin labeling (ASL),
      diffusion-weighted imaging (DWI), and diffusion-tensor imaging (DTI). BOLD and
      ASL provide different methods to evaluate skeletal muscle microperfusion. The
      BOLD signal reflects the ratio between oxyhemoglobin and deoxyhemoglobin. ASL
      uses selective tagging of inflowing blood spins in a specific region for
      calculating local perfusion. DWI and DTI provide information about the structural
      integrity of soft tissue including muscles and fibers as well as pathologies. 

PMID- 25953291
TI  - Advances in T1-weighted and T2-weighted imaging in the abdomen and pelvis.
AB  - Utilization of abdominopelvic MR imaging continues to increase in volume and gain
      widespread clinical acceptance. Many factors such as diaphragmatic respiratory
      motion, bulk patient motion, and the need for large volumetric coverage while
      maintaining clinically feasible scan times have proven challenging for body
      applications of MRI. However, many advances in MR acquisition, including non
      Cartesian T1-weighted and T2-weighted acquisitions, advanced Dixon sequences, and
      3-dimensional volumetric T2-weighted imaging have helped to mitigate some of the
      issues which have hampered abdominopelvic MR. This article will summarize these
      advances in T1-weighted and T2-weighted imaging, with an emphasis on clinical
      applications and implementation. 

PMID- 25953292
TI  - Recent Advances in MR Hardware and Software.
AB  - Tremendous advances have been made in abdominopelvic MR imaging, which continue
      to improve image quality, and make acquisitions faster and robust. We briefly
      discuss the role of non-Cartesian acquisition schemes as well as dual parallel
      radiofrequency (RF) transmit systems in the article to further improve image
      quality of the abdominal MR imaging. Furthermore, the use of hybrid PET/MR
      systems has the potential to synergistically combine MR imaging with PET
      acquisition, and the evolving role of hybrid PET/MR imaging is discussed. 

PMID- 25953290
TI  - Advances in diffusion-weighted imaging.
AB  - Diffusion-weighted imaging (DWI) has become a routine component of clinical MR
      imaging. Its unique soft tissue contrast mechanism exploits differences in the
      motion of water molecules in vivo at a biologically meaningful scale. The
      clinical potential of DWI in lesion detection, characterization, and response
      assessment has been explored. This review briefly covers basic principles of DWI
      and introduces advances, specifically for abdominopelvic organs.

PMID- 25953293
TI  - Advances in MR Imaging.

PMID- 25953294
TI  - A facile synthesis of Pt@Ir zigzag bimetallic nanocomplexes for hydrogenation
      reactions.
AB  - Bimetallic Pt@Ir zigzag nanocomplexes were successfully synthesized with a
      uniform morphology via the simple reduction of Ir(acac)3 on the surface of Pt
      nanorods. The novel Pt@Ir nanocomplexes exhibited good catalytic activity in
      hydrogenation reactions under mild conditions, such as the hydrogenation of
      nitroaromatic compounds. The highest yield of the obtained product achieved was
      ~99.9% using H2 as the sole reductant. 

PMID- 25953295
TI  - Pattern of tumor progression in liver cancer: The missing partner in trial
      design.

PMID- 25953297
TI  - The enduring effects of early-childhood adversities and troubled sleep among
      Canadian adults: a population-based study.
AB  - OBJECTIVE: Although many studies have consistently found that early-childhood
      adversities are important risk factors for physical and mental health problems
      later in adulthood, few have examined the association between early-childhood
      adversities and troubled sleep. The objective of this study was to examine the
      association between early-childhood adversities and troubled sleep among adult
      Canadians. METHODS: Data for this paper (N = 19,349) were obtained from
      Statistics Canada's 2012 Canadian Community Health Survey-Mental Health (CCHS
      MH). Logistic regression analysis was conducted to examine the association
      between early childhood adversities and troubled sleep, while accounting for
      various sociodemographic, socioeconomic, health, and mental health factors.
      RESULTS: Of the 19,349 respondents examined, 2748 representing 14.2% had troubled
      sleep. Controlling for sociodemographic, socioeconomic, health, and mental health
      factors, it was observed that for each additional childhood adversity
      experienced, the odds of having troubled sleep increased by 10% (odds ratio =
      1.10, p <0.001, 95% confidence interval = 1.07-1.13). In addition, psychological
      distress, older age, being female, being unmarried, being white, a lower annual
      income, chronic pain, poor perceived health, and mental health difficulties were
      associated with troubled sleep. CONCLUSION: The results of this paper provide
      population-based evidence for childhood adversities as a major predictor of
      troubled sleep in adulthood. The long-standing effects of these adversities on
      sleep highlight the importance of early detection, such as consistent assessment
      of sleep habits for children, adolescents, and adults, who have experienced
      childhood adversities, in health and mental health settings.

PMID- 25953296
TI  - FTY720 attenuates excitotoxicity and neuroinflammation.
AB  - BACKGROUND: FTY720 (fingolimod, GilenyaTM), a structural analog of sphingosine-1
      phosphate (S1P), is the first oral drug approved for treatment the relapsing
      remitting form of multiple sclerosis (MS), and its efficacy has been related to
      induced lymphopenia and consequent immunosuppression via modulation of S1P1
      receptors (S1P1R). However, due to its lipophilic nature, FTY720 crosses the
      blood brain barrier (BBB) and could act directly on neural cells. In this study,
      we investigated the effectiveness of FTY720 as a neuroprotective agent using in
      vitro and in vivo models of excitotoxic neuronal death and examined if FTY720
      exerts a direct action on neurons, or/and an indirect modulation of inflammation
      mediated neurodegeneration as a possible mechanism of neuroprotection. METHODS:
      Primary neuronal and organotypic cortical cultures were treated with N-methyl-D
      aspartic acid (NMDA) to induce excitotoxic cell death (measured by lactate
      dehydrogenase (LDH) assay or propidium iodide uptake, respectively). The effects
      of FTY720 treatment (10, 100 and 1,000 nM) on neuronal survival were examined. As
      an in vivo model of neuronal death and inflammation, we used
      intracerebroventricular (icv) administration of kainic acid (KA; 0.5 MUg/2 MUl)
      in Sprague-Dawley rats. FTY720 was applied icv (1 MUg/2 MUl), together with KA,
      plus intraperitoneally (ip; 1 mg/kg) 24 h before, and daily, until sacrifice 3
      days after icv. Rats were evaluated for neurological score, neuronal loss in CA3
      hippocampal region and activation of microglia at the lesion site. In addition,
      we tested FTY720 as a modulator of microglia responses using microglial cell
      cultures activated with lipopolysaccharide (LPS) and its effects in stress
      signalling pathways using western blotting for p38 and JNK1/2 mitogen-activated
      protein kinases (MAPKs). RESULTS: FTY720 was able to reduce excitotoxic neuronal
      death in vitro. Moreover, in vivo repeated FTY720 administration attenuated KA
      induced neurodegeneration and microgliosis at the CA3 lesion site. Furthermore,
      FTY720 negatively modulates p38 MAPK in LPS-activated microglia, whereas it had
      no effect on JNK1/2 activation. CONCLUSIONS: These data support a role for FTY720
      as a neuroprotective agent against excitotoxin-induced neuronal death and as a
      negative modulator of neuroinflammation by targeting the p38 MAPK stress
      signalling pathway in microglia.

PMID- 25953298
TI  - Impact of experimentally manipulated sleep on adolescent simulated driving.
AB  - OBJECTIVE/BACKGROUND: Sleep restriction (SR) impairs adolescents' attention,
      which could contribute to high rates of driving crashes. Here, we examine the
      impact of experimental SR on adolescent drivers, considering whether that impact
      is moderated by the nature of the drive (urban/suburban vs. rural) or how
      vulnerable each adolescent is to attentional decline after SR.
      PARTICIPANTS/METHODS: A total of 17 healthy 16-18-year-old licensed drivers
      completed two five-night sleep conditions: SR (6.5 h in bed) versus extended
      sleep (ES; 10 h in bed) in counterbalanced order. After each, participants
      completed rural and urban/suburban courses in a driving simulator, and parents
      rated participants' attention in day-to-day settings. Vulnerability to SR was
      computed as cross-condition change in parent ratings. Dependent variables
      included standard deviation (SD) of lateral lane position (SDLP), mean speed, SD
      of speed, and crashes. Multivariate models examined the main and interaction
      effects of sleep condition, driving environment, and vulnerability to SR,
      covarying for years licensed. RESULTS: Although the effects for the other
      outcomes were nonsignificant, there were three-way interactions (sleep * drive *
      vulnerability) for mean speed and SDLP (p <0.02). During the rural drive,
      adolescents had less consistent lateral vehicle control in SR than ES, despite
      slower driving among those reported to be vulnerable to SR. During the
      urban/suburban drive, SR worsened SDLP only among adolescents reported to be
      vulnerable to SR. CONCLUSIONS: These preliminary findings suggest that even a
      moderate degree of SR may be a modifiable contributor to adolescent driving
      problems for some. This impact is widely present during monotonous rural drives
      and in a subgroup during interesting urban/suburban drives.

PMID- 25953299
TI  - How are normal sleeping controls selected? A systematic review of cross-sectional
      insomnia studies and a standardized method to select healthy controls for sleep
      research.
AB  - There appears to be some inconsistency in how normal sleepers (controls) are
      selected and screened for participation in research studies for comparison with
      insomnia patients. The purpose of the current study is to assess and compare
      methods of identifying normal sleepers in insomnia studies, with reference to
      published standards. We systematically reviewed the literature on insomnia
      patients, which included control subjects. The resulting 37 articles were
      systematically reviewed with reference to the five criteria for normal sleep
      specified by Edinger et al. In summary, these criteria are as follows: evidence
      of sleep disruption, sleep scheduling, general health, substance/medication use,
      and other sleep disorders. We found sleep diaries, polysomnography (PSG), and
      clinical screening examinations to be widely used with both control subjects and
      insomnia participants. However, there are differences between research groups in
      the precise definitions applied to the components of normal sleep. We found that
      none of the reviewed studies applied all of the Edinger et al. criteria, and 16%
      met four criteria. In general, screening is applied most rigorously at the level
      of a clinical disorder, whether physical, psychiatric, or sleep. While the
      Edinger et al. criteria seem to be applied in some form by most researchers,
      there is scope to improve standards and definitions in this area. Ideally,
      different methods such as sleep diaries and questionnaires would be used
      concurrently with objective measures to ensure normal sleepers are identified,
      and descriptive information for control subjects would be reported. Here, we have
      devised working criteria and methods to be used for the assessment of normal
      sleepers. This would help clarify the nature of the control group, in contrast to
      insomnia subjects and other patient groups.

PMID- 25953300
TI  - Treatment of obstructive sleep apnea syndrome associated with stroke.
AB  - The association between sleep-disordered breathing and stroke has been a subject
      of increased interest and research. Obstructive sleep apnea (OSA) is an important
      risk factor for stroke incidence and mortality. Moreover, OSA is a common
      clinical outcome after stroke, directly influencing the patient's recovery. The
      treatment of choice for OSA is positive airway pressure (PAP) support and the PAP
      appliance is considered the most recommended clinical management for the
      treatment of patients with cardiovascular complications. However, the
      implementation of PAP in stroke patients remains a challenge, considering the
      increased frequency of motor and language impairments associated with the
      cerebrovascular event. In the present study, we reviewed the main findings
      describing the association between stroke and OSA treatment with continuous
      positive airway pressure. We also discussed the types of OSA treatment, the
      different options and indications of PAP treatment, PAP adherence and the
      clinical outcomes after treatment. 

PMID- 25953302
TI  - Cytokine gene polymorphisms in obstructive sleep apnoea/hypopnoea syndrome.
AB  - OBJECTIVE: The pro-inflammatory cytokines, TNF-alpha, IL-6, and IL-8 are elevated
      in obstructive sleep apnoea/hypopnoea syndrome (OSAHS). Cytokine gene
      interactions are complex and haplotype analysis may be more informative. We
      hypothesized that the effects of TNF-alpha in OSAHS might be due to linkage
      disequilibrium of the TNF-alpha (-308A) single nucleotide polymorphism (SNP) with
      other polymorphisms within the TNF-alpha gene, and that predisposition to
      elevated IL-6 and IL-8 levels in OSAHS might be attributable to pro-inflammatory
      IL-6 and IL-8 gene promoter polymorphisms. METHOD: 173 subjects were classified
      as having definite OSAHS or not on the basis of apnoea-hypopnoea frequency, sex,
      age, and symptoms. Population controls comprised 192 random UK blood donors.
      Genotyping was undertaken for the TNF-alpha promoter polymorphisms (-1031, -863, 
      857, -238), two lymphotoxin-alpha polymorphisms (intron 1 and Thr60Asn), the pro
      inflammatory IL-6 gene promoter polymorphism (-174), and IL-8 gene promoter
      polymorphisms (-251; -781). RESULTS: There was no significant difference between
      groups re: genotype/allelic frequency in the genes investigated. Association
      between disease status and the TNF-alpha alleles independently (TNF-103, TNF-803,
      TNF-857, TNF-238) with five haplotypes of TNF-alpha was not significant (p >
      0.05). There was no difference in allelic or genotypic frequencies between obese
      and non-obese subjects with OSAHS. The TNF-alpha (-863A) allele alone, was
      significantly associated with obesity (OR 2.4; CI95% 1.1-5; p = 0.025).
      CONCLUSION: Only the TNF-alpha (308A) SNP appears to be significantly associated
      with OSAHS. The impact of cytokine gene polymorphisms on phenotypic expression of
      inflammation in OSAHS is likely to be complex.

PMID- 25953301
TI  - First night of CPAP: impact on memory consolidation attention and subjective
      experience.
AB  - OBJECTIVE: Neurocognitive deficits are common and serious consequences of
      obstructive sleep apnea (OSA). Currently, the gold standard treatment is
      continuous positive air pressure (CPAP) therapy, although the clinical responses
      to this intervention can be variable. This study examined the effect of one night
      of CPAP therapy on sleep-dependent memory consolidation, attention, and vigilance
      as well as subjective experience. METHODS: Fifteen healthy controls and 29
      patients with obstructive sleep apnea of whom 14 underwent a full-night CPAP
      titration completed the psychomotor vigilance test (PVT) and motor sequence
      learning task (MST) in the evening and the morning after undergoing overnight
      polysomnography. All participants also completed subjective evaluations of sleep
      quality. RESULTS: Participants with OSA showed significantly less overnight
      improvement on the MST compared to controls without OSA, independent of whether
      or not they had received CPAP treatment, while there was no significant
      difference between the untreated OSA and CPAP-treated patients. Within the OSA
      group, only those receiving CPAP exhibited faster reaction times on the PVT in
      the morning. Compared to untreated OSA patients, they also felt subjectively more
      rested and reported that they slept better. CONCLUSION: Our results demonstrate
      an instant augmentation of subjective experience and, based on PVT results,
      attention and vigilance after one night of CPAP, but a lack of an effect on
      offline sleep-dependent motor memory consolidation. This dissociation may be
      explained by different brain structures underlying these processes, some of which
      might require longer continued adherence to CPAP to generate an effect.

PMID- 25953304
TI  - Complete genome sequence of Corynebacterium glutamicum B253, a Chinese lysine
      producing strain.
AB  - We disclosed the complete genome sequence of Corynebacterium glutamicum B253, an
      important lysine-producing strain in China. The genome consists a circular
      chromosome (3,159,203bp) and a plasmid (24,775bp), encoding 2767 protein coding
      genes in total. The genome contains all genes for lysine biosynthesis, and some
      mutations potentially relevant to lysine production were detected in comparison
      with sequence of other C. glutamicum. 

PMID- 25953305
TI  - Abducens nerve palsy during sepsis.

PMID- 25953303
TI  - Preserved cardiac autonomic dynamics during sleep in subjects with spinal cord
      injuries.
AB  - BACKGROUND: Spinal cord injuries (SCI) are associated with altered cardiovascular
      autonomic control (CAC). Sleep is characterized by modifications of autonomic
      control across sleep stages; however, no data are available in SCI subjects on
      CAC during sleep. We aim to assess cardiac autonomic modulation during sleep in
      subjects with SCI. PATIENTS AND METHODS: 27 participants with a neurological and
      radiological diagnosis of cervical (Cerv, n = 12, ie, tetraplegic) and thoracic
      SCI (Thor, n = 15, ie, paraplegic) and healthy subjects (Controls) were enrolled.
      Overnight polysomnographic (PSG) recordings were obtained in all participants.
      Electrocardiography and respiration were extracted from PSG, divided into sleep
      stages [wakefulness (W), non-REM sleep (NREM) and REM] for assessment of CAC,
      using symbolic analysis (SA) and corrected conditional entropy (CCE). SA
      identified indices of sympathetic and parasympathetic modulation and CCE
      evaluated the degree of complexity of the heart period time series. RESULTS: SA
      revealed a reduction of sympathetic and predominant parasympathetic control
      during NREM compared to W and REM in SCI patients, independent of the level of
      the lesion, similar to the Controls. In all three groups, complexity of autonomic
      regulation was higher in NREM compared to W and REM. CONCLUSIONS: In subjects
      with SCI, cardiac autonomic control changed across sleep stages, with a reduction
      of sympathetic and an increase of parasympathetic modulation during NREM compared
      to W and REM, and a parallel increase of complexity during NREM, which was
      similar to the Controls. Cardiac autonomic dynamics during sleep are maintained
      in SCI, independent of the level of the lesion.

PMID- 25953306
TI  - A telesurveillance system with automatic electrocardiogram interpretation based
      on support vector machine and rule-based processing.
AB  - BACKGROUND: Telehealth care is a global trend affecting clinical practice around
      the world. To mitigate the workload of health professionals and provide
      ubiquitous health care, a comprehensive surveillance system with value-added
      services based on information technologies must be established. OBJECTIVE: We
      conducted this study to describe our proposed telesurveillance system designed
      for monitoring and classifying electrocardiogram (ECG) signals and to evaluate
      the performance of ECG classification. METHODS: We established a telesurveillance
      system with an automatic ECG interpretation mechanism. The system included: (1)
      automatic ECG signal transmission via telecommunication, (2) ECG signal
      processing, including noise elimination, peak estimation, and feature extraction,
      (3) automatic ECG interpretation based on the support vector machine (SVM)
      classifier and rule-based processing, and (4) display of ECG signals and their
      analyzed results. We analyzed 213,420 ECG signals that were diagnosed by
      cardiologists as the gold standard to verify the classification performance.
      RESULTS: In the clinical ECG database from the Telehealth Center of the National
      Taiwan University Hospital (NTUH), the experimental results showed that the ECG
      classifier yielded a specificity value of 96.66% for normal rhythm detection, a
      sensitivity value of 98.50% for disease recognition, and an accuracy value of
      81.17% for noise detection. For the detection performance of specific diseases,
      the recognition model mainly generated sensitivity values of 92.70% for atrial
      fibrillation, 89.10% for pacemaker rhythm, 88.60% for atrial premature
      contraction, 72.98% for T-wave inversion, 62.21% for atrial flutter, and 62.57%
      for first-degree atrioventricular block. CONCLUSIONS: Through connected
      telehealth care devices, the telesurveillance system, and the automatic ECG
      interpretation system, this mechanism was intentionally designed for continuous
      decision-making support and is reliable enough to reduce the need for face-to
      face diagnosis. With this value-added service, the system could widely assist
      physicians and other health professionals with decision making in clinical
      practice. The system will be very helpful for the patient who suffers from
      cardiac disease, but for whom it is inconvenient to go to the hospital very
      often.

PMID- 25953307
TI  - Characterization of Brachypodium distachyon as a nonhost model against
      switchgrass rust pathogen Puccinia emaculata.
AB  - BACKGROUND: Switchgrass rust, caused by Puccinia emaculata, is an important
      disease of switchgrass, a potential biofuel crop in the United States. In severe
      cases, switchgrass rust has the potential to significantly affect biomass yield.
      In an effort to identify novel sources of resistance against switchgrass rust, we
      explored nonhost resistance against P. emaculata by characterizing its
      interactions with six monocot nonhost plant species. We also studied the genetic
      variations for resistance among Brachypodium inbred accessions and the
      involvement of various defense pathways in nonhost resistance of Brachypodium.
      RESULTS: We characterized P. emaculata interactions with six monocot nonhost
      species and identified Brachypodium distachyon (Bd21) as a suitable nonhost model
      to study switchgrass rust. Interestingly, screening of Brachypodium accessions
      identified natural variations in resistance to switchgrass rust. Brachypodium
      inbred accessions Bd3-1 and Bd30-1 were identified as most and least resistant to
      switchgrass rust, respectively, when compared to tested accessions. Transcript
      profiling of defense-related genes indicated that the genes which were induced in
      Bd21after P. emaculata inoculation also had higher basal transcript abundance in
      Bd3-1 when compared to Bd30-1 and Bd21 indicating their potential involvement in
      nonhost resistance against switchgrass rust. CONCLUSION: In the present study, we
      identified Brachypodium as a suitable nonhost model to study switchgrass rust
      which exhibit type I nonhost resistance. Variations in resistance response were
      also observed among tested Brachypodium accessions. Brachypodium nonhost
      resistance against P. emaculata may involve various defense pathways as indicated
      by transcript profiling of defense related genes. Overall, this study provides a
      new avenue to utilize novel sources of nonhost resistance in Brachypodium against
      switchgrass rust.

PMID- 25953308
TI  - Kinetics of hematogones in bone marrow samples from patients with non-Hodgkin
      lymphomas treated with rituximab-containing regimens: a flow cytometric study.
AB  - Treatment with rituximab, either alone or in combination with antiblastic drugs,
      causes significant depletion of circulating B-lymphocytes and modifications of B
      cell maturation in the bone marrow. In the present study, we analyzed the
      kinetics of hematogones in bone marrow samples from 55 patients suffering from
      non-Hodgkin lymphomas and treated with rituximab-containing regimens. Maturation
      arrest at the level of stage 2 hematogones, along with complete depletion of
      naive, mature B-lymphocytes, was observed as short-term effects (2 months after
      completion of chemo-immunotherapy). Further bone marrow samples, obtained 12
      months after the last rituximab infusion in 21 patients undergoing long-term
      follow-up and treated with rituximab maintenance therapy, showed complete
      normalization of B-lymphocyte ontogeny. Hypogammaglobulinemia developed in 26
      patients, and was still observed in nine of the 21 patients undergoing long-term
      follow-up. Our study provides novel data on hematogone kinetics in the setting of
      patients with non-Hodgkin lymphomas treated with chemo-immunotherapy containing
      rituximab and with rituximab maintenance. Our observations show that
      hypogammaglobulinemia can persist in a significant percentage of patients,
      despite complete recovery of B-lymphocyte ontogeny.

PMID- 25953309
TI  - Epstein-Barr virus-positive diffuse large B-cell lymphoma following acute myeloid
      leukemia: a common clonal origin indicated by chromosomal translocation
      t(3;4)(p25;q21).
AB  - Secondary non-Hodgkin lymphoma following acute myeloid leukemia (AML) is
      extremely rare. We here describe a unique case involving a patient who developed
      Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) during
      complete remission (CR) of AML. A 75-year-old Japanese man was initially
      diagnosed with AML with maturation (FAB M2), bearing chromosomal translocation
      t(3,4)(p25;q21). After intensive chemotherapy, bone marrow aspiration revealed
      normal karyotype, and he achieved CR. Six years and 4 months later, he was still
      in CR from AML, but developed DLBCL presenting in the terminal ileum. Cytogenetic
      analysis of the DLBCL cells showed the same translocation as the previous AML.
      The rearrangements of the immunoglobulin heavy chain genes of the two
      malignancies were examined using polymerase chain reaction amplification, and the
      rearrangement patterns were found to differ from each other. Our data thus
      suggest that, in the present case, the AML and DLBCL arose from a common
      progenitor cell, as indicated by the clonal abnormality t(3,4)(p25;q21), and that
      different immunoglobulin heavy chain gene rearrangements occurred during each
      course of clonal evolution.

PMID- 25953310
TI  - Comparison of the backbone dynamics of wild-type Hydrogenobacter thermophilus
      cytochrome c(552) and its b-type variant.
AB  - Cytochrome c552 from the thermophilic bacterium Hydrogenobacter thermophilus is a
      typical c-type cytochrome which binds heme covalently via two thioether bonds
      between the two heme vinyl groups and two cysteine thiol groups in a CXXCH
      sequence motif. This protein was converted to a b-type cytochrome by substitution
      of the two cysteine residues by alanines (Tomlinson and Ferguson in Proc Natl
      Acad Sci USA 97:5156-5160, 2000a). To probe the significance of the covalent
      attachment of the heme in the c-type protein, (15)N relaxation and hydrogen
      exchange studies have been performed for the wild-type and b-type proteins. The
      two variants share very similar backbone dynamic properties, both proteins
      showing high (15)N order parameters in the four main helices, with reduced values
      in an exposed loop region (residues 18-21), and at the C-terminal residue Lys80.
      Some subtle changes in chemical shift and hydrogen exchange protection are seen
      between the wild-type and b-type variant proteins, not only for residues at and
      neighbouring the mutation sites, but also for some residues in the heme binding
      pocket. Overall, the results suggest that the main role of the covalent linkages
      between the heme group and the protein chain must be to increase the stability of
      the protein.

PMID- 25953311
TI  - An extended combinatorial 15N, 13Calpha, and 13C' labeling approach to protein
      backbone resonance assignment.
AB  - Solution NMR studies of alpha-helical membrane proteins are often complicated by
      severe spectral crowding. In addition, hydrophobic environments like detergent
      micelles, isotropic bicelles or nanodiscs lead to considerably reduced molecular
      tumbling rates which translates into line-broadening and low sensitivity. Both
      difficulties can be addressed by selective isotope labeling methods. In this
      publication, we propose a combinatorial protocol that utilizes four different
      classes of labeled amino acids, in which the three backbone heteronuclei (amide
      nitrogen, alpha-carbon and carbonyl carbon) are enriched in (15)N or (13)C
      isotopes individually as well as simultaneously. This results in eight different
      combinations of dipeptides giving rise to cross peaks in (1)H-(15)N correlated
      spectra. Their differentiation is achieved by recording a series of HN-detected
      2D triple-resonance spectra. The utility of this new scheme is demonstrated with
      a homodimeric 142-residue membrane protein in DHPC micelles. Restricting the
      number of selectively labeled samples to three allowed the identification of the
      amino-acid type for 77 % and provided sequential information for 47 % of its
      residues. This enabled us to complete the backbone resonance assignment of the
      uniformly labeled protein merely with the help of a 3D HNCA spectrum, which can
      be collected with reasonable sensitivity even for relatively large, non
      deuterated proteins.

PMID- 25953312
TI  - Assignment of methyl NMR resonances of a 52 kDa protein with residue-specific 4D
      correlation maps.
AB  - Methyl groups have become key probes for structural and functional studies by
      nuclear magnetic resonance. However, their NMR signals cluster in a small
      spectral region and assigning their resonances can be a tedious process. Here, we
      present a method that facilitates assignment of methyl resonances from assigned
      amide groups. Calculating the covariance between sensitive methyl and amide 3D
      spectra, each providing correlations to C(alpha) and C(beta) separately, produces
      4D correlation maps directly correlating methyl groups to amide groups. Optimal
      correlation maps are obtained by extracting residue-specific regions, applying
      derivative to the dimensions subject to covariance, and multiplying 4D maps
      stemming from different 3D spectra. The latter procedure rescues weak signals
      that may be missed in traditional assignment procedures. Using these covariance
      correlation maps, nearly all assigned isoleucine, leucine, and valine amide
      resonances of a 52 kDa nonribosomal peptide synthetase cyclization domain were
      paired with their corresponding methyl groups.

PMID- 25953313
TI  - Impact of delayed lymphoscintigraphy for sentinel lymphnode biopsy for breast
      cancer.
AB  - BACKGROUND: Despite universal adoption of sentinel lymph node biopsy (SLNB) for
      breast cancer, there remains no standardized protocol for preoperative
      lymphoscintographic assessment of sentinel nodes. Both immediate and delayed
      lymphoscintigraphy are currently utilized, although it is unclear how delayed
      imaging impacts SLN identification. METHODS: Among patients diagnosed with breast
      cancer who underwent SLNB at Duke from 2011 to 2012, two protocols for
      preoperative lymphoscintigraphy were used: protocol A included both immediate and
      delayed lymphoscintigraphy (n = 152), while protocol B involved immediate
      lymphoscintigraphy only (n = 103). RESULTS: The overall intraoperative SLN
      identification rate was 98.4% and did not differ between groups. A lower number
      of SLN were visualized on the immediate scan using protocol A compared to
      protocol B (P < 0.001). Although a greater total number of nodes was excised
      using protocol A, this result was not statistically significant (P = 0.08).
      Moreover, there was no significant difference in the number of negative SLN
      between groups (P = 0.51). CONCLUSIONS: We found no significant impact on
      identification rate or number of SLN excised with the use of delayed versus
      immediate imaging. These findings support abandoning delayed lymphoscintographic
      imaging, except in those cases where aberrant drainage is suspected.

PMID- 25953314
TI  - A comparative study of the effects of different low-level lasers on the
      proliferation, viability, and migration of human melanocytes in vitro.
AB  - The aim of this study was to investigate the effects of different low-level laser
      therapies (LLLTs) of various wavelengths and energies on normal cultured human
      melanocytes. Various studies have shown the effects of LLLs on various types of
      cultured cells. Presently, little is known about the biological effects of LLLTs
      on melanocytes. Melanocytes were exposed to LLLT at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0,
      3.5, 4.0, 4.5, or 5.0 J/cm(2) using a blue (457 nm), red (635 nm), or ultraviolet
      (UV) (355 nm) laser. Melanocyte viability, proliferation, and migration were
      monitored at 72 h after irradiation. The blue (P < 0.001) and red (P < 0.001 and
      P < 0.01) lasers significantly enhanced viability at 0.5 to 2.0 J/cm(2), whereas
      the UV laser (P < 0.001) could significantly enhance viability only at 0.5 and
      1.0 J/cm(2) compared with controls. The blue and red lasers also significantly
      enhanced the proliferation of the melanocytes at 0.5 to 2.0 J/cm(2) (P < 0.001),
      and the UV laser significantly enhanced proliferation at 0.5 to 1.5 J/cm(2) (P <
      0.001 and P < 0.01) compared with controls. The blue laser significantly enhanced
      melanocyte migration at 0.5 to 4.0 J/cm(2) (P < 0.001 to P < 0.05), but the red
      (P < 0.001 and P < 0.01) and UV (P < 0.001 to P < 0.05) lasers could
      significantly enhance such migration at 0.5 to 1.0 J/cm(2) and 0.5 to 2.0
      J/cm(2), respectively, compared with controls. LLLT at low energy densities is
      able to significantly increase melanocyte viability, proliferation, and migration
      in vitro, and at higher energy densities, it gives non-stimulatory results.
      Additionally, the blue laser was the best among the three lasers. These findings
      might have potential application in vitiligo treatment in future. 

PMID- 25953315
TI  - Correlates of participation in meaningful activities among people with multiple
      sclerosis.
AB  - OBJECTIVE: To explore the associations between impairments, self-management self
      efficacy, self-management behaviors, and environmental factors and their role in
      predicting participation in meaningful activities among people with multiple
      sclerosis. DESIGN: Online cross-sectional survey. SUBJECTS/PATIENTS: Randomly
      selected individuals (n = 335) from a large multiple sclerosis patient registry.
      METHODS: Participation in activities that are meaningful to the individual was
      measured with Community Participation Indicators (CPI), the dependent variable.
      Independent variables included symptom severity, activities of daily living
      limitations, cognitive problems, stages of change for physical activity,
      nutritional behaviors, self-efficacy, and environmental barriers. A backwards
      selection regression analysis was used to compare the relative contributions of
      independent variables in predicting the CPI. A path analysis was conducted to
      explore the associations between independent variables and their direct and
      indirect effects on the CPI. RESULTS: The final regression model included self
      management self-efficacy (beta = 0.12), environmental barriers (beta = -0.16),
      cognitive problems (beta = -0.22), and stages of change for physical activity
      (beta = 0.12). Path analysis indicated that impairments and environmental
      barriers might negatively influence self-management self-efficacy. Self
      management self-efficacy might have indirect effects on the CPI via engagement in
      self-management behaviors. CONCLUSION: Future research should explore whether
      interventions that promote self-management self-efficacy can facilitate
      participation in meaningful activities.

PMID- 25953316
TI  - Lived experiences of breast cancer survivors after diagnosis, treatment and
      beyond: qualitative study.
AB  - BACKGROUND: The number of breast cancer survivors has increased since 1990 due to
      advances in biomedical technology that lead to an increase in early diagnosis and
      treatment. Research on survivorship has focused on the psychological and
      treatment aspects of the disease. The goal of this study was focused on exploring
      the lived experiences of breast cancer survivors from diagnosis, treatment and
      beyond. OBJECTIVE: To understand the lived experiences of women who are breast
      cancer survivors. DESIGN, SETTING AND PARTICIPANTS: A purposive sampling strategy
      was used to recruit participants from two Missouri cancer centres. A total of 15
      women breast cancer survivors were interviewed. FINDINGS: Three major themes
      emerged that described the lived experiences of the women. These were factors
      from the diagnosis and treatment management impacting survivorship, relationship
      and support system and implication of survivorship. Participants noted that
      coping with the diagnosis and treatment was a stressful journey and required lots
      of adjustment and changes. Some developed various techniques such as journaling
      their activities which provided comfort. In addition, support from family was
      shared as the key which gave them strength and courage through the different
      stages of treatment. However, they found it difficult to articulate what
      survivorship meant. CONCLUSION: Using in-depth interview techniques, this study
      shed light on the experiences of women who were diagnosed with breast cancer and
      have completed treatment. They acknowledged frustration with their diagnosis and
      body changes. Support received from family and friends helped them cope through
      their treatment. However, they felt abandoned once the treatment phase was over
      and were uncertain what survivorhood meant to them.

PMID- 25953318
TI  - Podocyte hypertrophy precedes apoptosis under experimental diabetic conditions.
AB  - Podocyte hypertrophy and apoptosis are two hallmarks of diabetic glomeruli, but
      the sequence in which these processes occur remains a matter of debate. Here we
      investigated the effects of inhibiting hypertrophy on apoptosis, and vice versa,
      in both podocytes and glomeruli, under diabetic conditions. Hypertrophy and
      apoptosis were inhibited using an epidermal growth factor receptor inhibitor (PKI
      166) and a pan-caspase inhibitor (zAsp-DCB), respectively. We observed
      significant increases in the protein expression of p27, p21, phospho-eukaryotic
      elongation factor 4E-binding protein 1, and phospho-p70 S6 ribosomal protein
      kinase, in both cultured podocytes exposed to high-glucose (HG) medium, and
      streptozotocin-induced diabetes mellitus (DM) rat glomeruli. These increases were
      significantly inhibited by PKI 166, but not by zAsp-DCB. In addition, the amount
      of protein per cell, the relative cell size, and the glomerular volume were all
      significantly increased under diabetic conditions, and these changes were also
      blocked by treatment with PKI 166, but not zAsp-DCB. Increased protein expression
      of cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase, together with
      increased Bax/Bcl-2 ratios, were also observed in HG-stimulated podocytes and DM
      glomeruli. Treatment with either zAsp-DCB or PKI 166 resulted in a significant
      attenuation of these effects. Both PKI 166 and zAsp-DCB also inhibited the
      increase in number of apoptotic cells, as assessed by Hoechst 33342 staining and
      TUNEL assay. Under diabetic conditions, inhibition of podocyte hypertrophy
      results in attenuated apoptosis, whereas blocking apoptosis has no effect on
      podocyte hypertrophy, suggesting that podocyte hypertrophy precedes apoptosis. 

PMID- 25953319
TI  - Assessing upper extremity capacity as a potential indicator of needs related to
      household activities for rehabilitation services in people with myotonic
      dystrophy type 1.
AB  - This study aimed to assess upper extremity capacity as a potential indicator of
      needs related to household activities for rehabilitation services in people with
      myotonic dystrophy type 1 (DM1). A cross-sectional study was set in an outpatient
      neuromuscular clinic where 200 adults with a confirmed diagnosis of DM1 (121
      women; mean age: 47 y) were selected from the registry of a neuromuscular clinic
      to participate. Housing-related activities were assessed using the "housing"
      section of the Assessment of Life Habits Questionnaire (LIFE-H). The upper
      extremity assessment included grip strength (Jamar dynamometer), lateral pinch
      strength (pinch gauge), gross dexterity (Box and Block Test) and fine dexterity
      (Purdue Pegboard Test). Correlations with the LIFE-H item "housing" were stronger
      for grip and lateral strength (r = 0.62; 0.61). When difficulties were present in
      "housing", the cut-off score associated with lateral pinch strength was 4.8 kg
      (sensitivity: 75.6%; specificity: 79.2%). Grip strength presented cut-off scores
      that clinically differed by gender. In conclusion, potential indicator of needs
      related to household activities for rehabilitation services with valid assessment
      tools were developed for people with DM1 who experience difficulties in housing
      related activities. These criteria will assist health professionals in their
      attempt to refer DM1 patients to rehabilitation services at the appropriate time.

PMID- 25953317
TI  - Regulation of viability, differentiation and death of human melanoma cells
      carrying neural stem cell biomarkers: a possibility for neural trans
      differentiation.
AB  - During embryonic development, melanoblasts, the precursors of melanocytes, emerge
      from a subpopulation of the neural crest stem cells and migrate to colonize skin.
      Melanomas arise during melanoblast differentiation into melanocytes and from
      young proliferating melanocytes through somatic mutagenesis and epigenetic
      regulations. In the present study, we used several human melanoma cell lines from
      the sequential phases of melanoma development (radial growth phase, vertical
      growth phase and metastatic phase) to compare: (i) the frequency and efficiency
      of the induction of cell death via apoptosis and necroptosis; (ii) the presence
      of neural and cancer stem cell biomarkers as well as death receptors, DR5 and
      FAS, in both adherent and spheroid cultures of melanoma cells; (iii) anti
      apoptotic effects of the endogenous production of cytokines and (iv) the ability
      of melanoma cells to perform neural trans-differentiation. We demonstrated that
      programed necrosis or necroptosis, could be induced in two metastatic melanoma
      lines, FEMX and OM431, while the mitochondrial pathway of apoptosis was prevalent
      in a vast majority of melanoma lines. All melanoma lines used in the current
      study expressed substantial levels of pluripotency markers, SOX2 and NANOG. There
      was a trend for increasing expression of Nestin, an early neuroprogenitor marker,
      during melanoma progression. Most of the melanoma lines, including WM35, FEMX and
      A375, can grow as a spheroid culture in serum-free media with supplements. It was
      possible to induce neural trans-differentiation of 1205Lu and OM431 melanoma
      cells in serum-free media supplemented with insulin. This was confirmed by the
      expression of neuronal markers, doublecortin and beta3-Tubulin, by significant
      growth of neurites and by the negative regulation of this process by a dominant
      negative Rac1N17. These results suggest a relative plasticity of differentiated
      melanoma cells and a possibility for their neural trans-differentiation without
      the necessity for preliminary dedifferentiation. 

PMID- 25953320
TI  - 50 years to diagnosis: Autosomal dominant tubular aggregate myopathy caused by a
      novel STIM1 mutation.
AB  - Tubular aggregates in human muscle biopsies have been reported to occur in a
      variety of acquired and hereditary neuromuscular conditions since 1964. Recently
      mutations in the gene encoding the main calcium sensor in the sarcoplasmic
      reticulum, stromal interaction molecule 1 (STIM1), have been identified as a
      cause of autosomal dominant tubular aggregate myopathy. We studied a German
      family with tubular aggregate myopathy and defined cellular consequences of
      altered STIM1 function. Both patients in our family had early progressive
      myopathy with proximal paresis of arm and leg muscles, scapular winging,
      ventilatory failure, joint contractures and external ophthalmoplegia. One patient
      had a well-documented disease course over 50 years. Sequencing of the STIM1 gene
      revealed a previously unreported missense mutation (c.242G>A; p.Gly81Asp) located
      in the first calcium binding EF domain. Functional characterization of the new
      STIM1 mutation by calcium imaging revealed that calcium influx was significantly
      increased in primary myoblasts of the index patient compared to controls pointing
      at a severe alteration of intracellular calcium homeostasis. This new family
      widens the spectrum of STIM1-associated myopathies to a more severe phenotype. 

PMID- 25953322
TI  - The effect of cycling deflection on the injection-molded thermoplastic denture
      base resins.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of cycling deflection
      on the flexural behavior of injection-molded thermoplastic resins. MATERIALS AND
      METHODS: Six injection-molded thermoplastic resins (two polyamides, two
      polyesters, one polycarbonate, one polymethyl methacrylate) and, as a control, a
      conventional heat-polymerized denture based polymer of polymethyl methacrylate
      (PMMA) were used in this study. The cyclic constant magnitude (1.0 mm) of 5000
      cycles was applied using a universal testing machine to demonstrate
      plasticization of the polymer. Loading was carried out in water at 23oC with
      eight specimens per group (n = 8). Cycling load (N) and deformation (mm) were
      measured. RESULTS: Force required to deflect the specimens during the first
      loading cycle and final loading cycle was statistically significantly different
      (p < 0.05) with one polyamide based polymer (Valplast) and PMMA based polymers
      (Acrytone and Acron). The other polyamide based polymer (LucitoneFRS), polyester
      based polymers (EstheShot and EstheShotBright) and polycarbonate based polymer
      (ReigningN) did not show significant differences (p > 0.05). None of the
      materials fractured during the loading test. One polyamide based polymer
      (Valplast) displayed the highest deformation and PMMA based polymers (Acrytone
      and Acron) exhibited the second highest deformation among the denture base
      materials. CONCLUSION: It can be concluded that there were considerable
      differences in the flexural behavior of denture base polymers. This may
      contribute to the fatigue resistance of the materials.

PMID- 25953324
TI  - How Do Women with an Intellectual Disability Experience the Support of a Doula
      During Their Pregnancy, Childbirth and After the Birth of Their Child?
AB  - BACKGROUND: With increasing numbers of people with an intellectual disability
      choosing to become parents, the right support is imperative for effective
      parenting (Macintyre & Stewart ). The aim of this study was to gain insight into
      the experiences of parents who received support from Doulas during pregnancy,
      birth and following the birth of their child. In addition, the experiences of the
      Doulas who provided the support were investigated. MATERIALS AND METHODS: Four
      women with an intellectual disability who received Doula support were interviewed
      before and after the birth of their child. Three Doulas were interviewed after
      the birth about their experiences of supporting women with an intellectual
      disability. RESULTS: Interview transcripts were analysed using Interpretive
      Phenomenological Analysis (IPA). Themes were identified from each interview,
      before an overall analysis of themes from each support phase was undertaken.
      CONCLUSIONS: Pre-natally, the Doula was considered helpful and a reliable source
      of information about pregnancy. Each mother perceived Doula support as a means of
      keeping her child in her care. Post-natally, mothers described a trusting
      relationship with their Doula, who enabled them to make informed choices. Doulas
      described how they adapted their work to meet the needs of parents with
      intellectual disability. Being involved in Child Protection procedures was
      perceived as stressful and challenging.

PMID- 25953321
TI  - Adenovirus-Vectored Broadly Neutralizing Antibodies Directed Against gp120
      Prevent Human Immunodeficiency Virus Type 1 Acquisition in Humanized Mice.
AB  - Despite nearly three decades of research, a safe and effective vaccine against
      human immunodeficiency virus type 1 (HIV-1) has yet to be achieved. More
      recently, the discovery of highly potent anti-gp160 broadly neutralizing
      antibodies (bNAbs) has garnered renewed interest in using antibody-based
      prophylactic and therapeutic approaches. Here, we encoded bNAbs in first
      generation adenoviral (ADV) vectors, which have the distinctive features of a
      large coding capacity and ease of propagation. A single intramuscular injection
      of ADV-vectorized bNAbs in humanized mice generated high serum levels of bNAbs
      that provided protection against multiple repeated challenges with a high dose of
      HIV-1, prevented depletion of peripheral CD4(+) T cells, and reduced plasma viral
      loads to below detection limits. Our results suggest that ADV vectors may be a
      viable option for the prophylactic and perhaps therapeutic use of bNAbs in
      humans. 

PMID- 25953325
TI  - A handheld flow genetic analysis system (FGAS): towards rapid, sensitive,
      quantitative and multiplex molecular diagnosis at the point-of-care level.
AB  - A handheld flow genetic analysis system (FGAS) is proposed for rapid, sensitive,
      multiplex and real-time quantification of nucleic acids at the point-of-care
      (POC) level. The FGAS includes a helical thermal-gradient microreactor and a
      microflow actuator, as well as control circuitry for temperature, fluid and power
      management, and smartphone fluorescence imaging. All of these features are
      integrated into a field-portable and easy-to-use molecular diagnostic platform
      powered by lithium batteries. Due to the unique design of the microreactor, not
      only steady temperatures for denaturation and annealing/extension but also a
      linear thermal gradient for spatial high-resolution melting can be achieved
      through simply maintaining a single heater at constant temperature. The
      smartphone fluorescence imaging system has a wide field of view that captures all
      PCR channels of the microreactor in a single snapshot without the need for any
      mechanical scanning. By these designs, the FGAS enables real-time monitoring of
      the temporal and spatial fluorescence signatures of amplicons during continuous
      flow amplification. On the current FGAS, visual detection of as little as 10
      copies per MUL of genomic DNA of Salmonella enterica was achieved in 15 min, with
      real-time quantitative detection of the DNA over 6 orders of magnitude
      concentration from 10(6) to 10(1) copies per MUL also completed in 7.5-15 min. In
      addition, multiple pathogenic DNA targets could be simultaneously discriminated
      with direct bar-chart readout or multiplex spatial melting in serial flow. We
      anticipate that the FGAS has great potential to become a next-generation gene
      analyzer for POC molecular diagnostics. 

PMID- 25953326
TI  - GMC's supposedly independent training review included secret meetings with
      politicians.

PMID- 25953328
TI  - Protein Kinase C Is Involved in the Induction of ATP-Binding Cassette Transporter
      A1 Expression by Liver X Receptor/Retinoid X Receptor Agonist in Human
      Macrophages.
AB  - The transcription of the ATP-binding cassette transporter A1 (ABCA1) gene, which
      plays a key anti-atherogenic role, is known to be induced by agonists of liver X
      receptors (LXRs). LXRs form obligate heterodimers with retinoid X receptors
      (RXRs) and interact with their recognition sequences in the regulatory regions of
      key genes implicated in the control of cholesterol, fatty acid and glucose
      homeostasis. We have previously shown a novel role for c-Jun N-terminal kinase
      (JNK) and phosphoinositide 3-kinase (PI3K) in the LXRs-mediated induction of
      macrophage gene expression. Protein kinase C (PKC) is often found to regulate the
      action of nuclear receptors and cross talk between this kinase family and JNK
      and/or PI3K has been shown in several settings. We have therefore investigated a
      potential role for PKC in the action of LXR/RXR agonist 22-(R)-hydroxycholesterol
      (22-(R)-HC)/9-cis-retinoic acid (9cRA) in THP-1 macrophages, including the
      induction of ABCA1 expression. The pan PKC inhibitor bisindoylmaleimide was found
      to attenuate the induction of ABCA1 protein expression, the activation of the JNK
      signaling pathway and the stimulation of activator protein-1 (AP-1) DNA binding
      activity in macrophages treated with 22-(R)-HC and 9cRA. The role of PKC in the
      action of these ligands was confirmed further by the use of more isotype-specific
      inhibitors. These studies therefore reveal a potentially important role for PKC
      in the action of 22-(R)-HC and 9cRA in human macrophages. This article is
      protected by copyright. All rights reserved.

PMID- 25953327
TI  - Circulating cytotoxic T cells and natural killer cells as potential predictors
      for antidepressant response in melancholic depression. Restoration of T
      regulatory cell populations after antidepressant therapy.
AB  - RATIONALE: There is a substantial unmet need for biomarkers to predict treatment
      response in major depressive disorder (MDD). Evidence has converged on activation
      of the inflammatory response system as a fundamental mechanism underlying MDD.
      OBJECTIVES: By investigating circulating leukocyte subsets quantified by
      fluorescence-activated cell sorting (FACS) analysis before treatment, we aim to
      predict antidepressant response. METHODS: Forty medication-free inpatients with
      melancholic, non-psychotic depression before treatment with either venlafaxine or
      imipramine and 40 age- and gender-matched healthy controls were included.
      Leukocyte subsets were quantified by FACS analysis using frozen peripheral blood
      mononuclear cells (PBMC) collected prior to and after 7 weeks of treatment with
      either venlafaxine (375 mg/day) or imipramine (blood level 200-300 ng/ml).
      Response was defined as at least 50 % reduction of the baseline Hamilton Rating
      Scale for Depression (HAM-D) score. RESULTS: Prior to treatment, MDD patients
      showed reduced percentages of CD4(+)CD25(high)Foxp3(+) T regulatory (Treg) cells
      when compared with controls (1.5 +/- 0.6 vs. 1.8 +/- 0.6, p = .037). After
      treatment, robust rises in Treg cells were observed in patients (1.8 +/- 0.7, p <
      .001), yet Treg cells were not predictors of the clinical outcome of treatment.
      Antidepressant non-responders showed increased CD8(+) cytotoxic T cell
      percentages (24.0 +/- 8.6 vs. 15.9 +/- 5.9, p = .004) and decreased natural
      killer (NK) cell percentages (14.0 +/- 6.9 vs. 21.4 +/- 11.9, p = .020) compared
      with responders before treatment. Both lymphocyte levels were not significantly
      modulated by treatment. CONCLUSION: In melancholic MDD, FACS analysis of
      circulating leukocyte subpopulations might help to discriminate between patients
      with high or low responsiveness to antidepressant treatment.

PMID- 25953329
TI  - Dimensionally stable and bioactive membrane for guided bone regeneration: An in
      vitro study.
AB  - Composite fibrous electrospun membranes based on poly(dl-lactide) (PLA) and
      poly(epsilon-caprolactone) (PCL) were engineered to include borate bioactive
      glass (BBG) for the potential purposes of guided bone regeneration (GBR). The
      fibers were characterized using scanning and transmission electron microscopies,
      which respectively confirmed the submicron fibrous arrangement of the membranes
      and the successful incorporation of BBG particles. Selected mechanical properties
      of the membranes were evaluated using the suture pullout test. The addition of
      BBG at 10 wt % led to similar stiffness, but more importantly, it led to a
      significantly stronger (2.37 +/- 0.51 N mm) membrane when compared with the
      commercially available Epiguide(r) (1.06 +/- 0.24 N mm) under hydrated
      conditions. Stability (shrinkage) was determined after incubation in a phosphate
      buffer solution from 24 h up to 9 days. The dimensional stability of the PLA:PCL
      based membranes with or without BBG incorporation (10.07-16.08%) was similar to
      that of Epiguide (14.28%). Cell proliferation assays demonstrated a higher rate
      of preosteoblasts proliferation on BBG-containing membranes (6.4-fold) over BBG
      free membranes (4- to 5.8-fold) and EpiGuide (4.5-fold), following 7 days of in
      vitro culture. Collectively, our results demonstrated the ability to synthesize,
      via electrospinning, stable, polymer-based submicron fibrous BBG-containing
      membranes capable of sustaining osteoblastic attachment and proliferation-a
      promising attribute in GBR.

PMID- 25953330
TI  - Chronic Lower Limb Wound Outcomes Among Rural and Urban Veterans.
AB  - PURPOSE: Veterans in rural areas generally have lower health care utilization
      than veterans in urban areas, but the impact of this difference on health
      outcomes has received little study. Chronic wounds provide a model for studying
      access to complex chronic care since they often are related to underlying health
      conditions and require lengthy treatment. Our goals were to describe chronic
      wound care utilization among rural and urban veterans and to determine the
      association between rural residence and wound healing. METHODS: We conducted a
      retrospective cohort study of 160 rural and 160 urban veterans in the Pacific
      Northwest with an incident of chronic lower limb wound between October 1, 2006,
      and September 30, 2007. We followed individuals for up to 1 year, measuring wound
      care utilization within Veterans Health Administration and Medicare. We compared
      wound healing using a competing risks proportional hazards model accounting for
      amputation and death. FINDINGS: Rural veterans had fewer outpatient wound care
      visits (6.8 vs 9.9) than urban veterans and a similar number of inpatient wound
      care stays (0.9 and 0.8, respectively). During follow-up, 234 veterans' wounds
      healed (77% rural, 69% urban). The adjusted hazard ratio for wound healing was
      1.11 (95% confidence intervals [CI]: 0.84-1.47, P = .45) for rural compared to
      urban veterans. The hazard of amputation was higher among rural veterans (hazard
      ratio [HR] = 2.65, 95% CI: 1.02-6.87, P = .045) and the hazard of death was lower
      (HR = 0.35, 95% CI: 0.12-0.97, P = .043). CONCLUSIONS: Despite lower wound care
      utilization, rural veterans' wounds were as likely to heal as urban veterans'
      wounds.

PMID- 25953331
TI  - Biodistribution of size-selected lyophilisomes in mice.
AB  - Lyophilisomes are a novel class of proteinaceous biodegradable nano/microparticle
      capsules developed for tumor drug delivery. The in vivo characteristics of
      lyophilisomes are unknown and, therefore, the time course of biodistribution of
      sized albumin-based lyophilisomes in CD1 mice after intravenous administration
      was studied. Lyophilisomes, prepared from Dylight680-labeled albumin, were sized
      using a sucrose gradient centrifugation methodology and four fractions with a
      mean size of approximately 200nm, 400nm, 550nm, and 650nm were pooled for in/ex
      vivo localization, (immuno)histochemistry and biochemical analysis. Lyophilisomes
      were rapidly taken out of the circulation by the liver and spleen.
      Immunohistochemistry revealed that lyophilisomes were taken up in the liver by
      F4/80 positive macrophages, and in the spleen by Sign-R1 positive macrophages
      specifically located in the marginal zones. Lyophilisomes were most likely
      degraded by the liver and spleen and subsequently excreted via the urine, as high
      levels of degraded Dylight680-labeled albumin were detected in the urine. This
      was corroborated by electron microscopy of the spleen, which showed intact
      lyophilisomes in the marginal zone 5 and 30min after injection, but not after 2h.
      In conclusion, IV injected lyophilisomes are rapidly entrapped by liver and
      splenic macrophages, biodegraded, and excreted in the urine. 

PMID- 25953332
TI  - Graphene-Skeleton Heat-Coordinated and Nanoamorphous-Surface-State Controlled
      Pseudo-Negative-Photoconductivity of Tiny SnO2 Nanoparticles.
AB  - SnO2 nanoparticles display a pseudo-negative-photoconductivity (PsdNPC) effect,
      which shows that their resistance increases under light irradiation via a heating
      effect. The PsdNPC originates from intensive electron scattering of the
      nanoamorphous surface state of the SnO2 nanoparticles, resulting in a small inner
      current and a large absorption of moisture, leading to a large surface current.
      Graphene as the inner skeleton can shorten the response and recovery times. 

PMID- 25953333
TI  - Morphological and functional analysis of a cohort of patients undergoing
      orthotopic ileal neobladder.
AB  - INTRODUCTION: This study was conducted between January 2001 and December 2013 to
      evaluate patient's outcomes after radical cystectomy and orthotopic ileal
      neobladder from a morphological and functional point of view at a median follow
      up of 2 years. MATERIALS AND METHODS: A total of 48 eligible patents were
      included. We first report our technical modifications to Studer's neobladder.
      Sequently, after a medium follow-up of two years, we assessed morphology of the
      reservoir and voiding functionality of this patients cohort, submitting them to
      specific questionnaires and to uroflowmetry. RESULTS: Early and late
      postoperative data are available for 36 patients. From the morphological follow
      up, 2 years after surgery, six patients had hydroureteronephrosis for vescico
      ureteral reflux in four cases (11% of total) and uretero-neobladder anastomosis
      stenosis in the other two (5.6% of total). Neobladder shape always remained
      spherical, with a relative right lateralization in eight cases (22.2%). Regarding
      the nine patients subjected to uroflowmetry, seven (77.7%) highlighted the lack
      of postvoid residual urine, with a maximum urinary flow rate within the normal
      range in six of them. DISCUSSION: Improvements in surgical technique may help to
      reduce complications rate. From uroflowmetry analysis, we can observe that the
      mean filling pressure following surgery was relatively stable and urinary flow
      rate was mostly satisfactory. In patients without postvoid residual urine, all
      referred absence of daily incontinence and good quality of life. CONCLUSION: From
      this morpho-functional evaluation, our orthotopic Studer-modified ileal
      neobladder seems an ideal solution for urinary diversion, presenting functional
      features similar to native bladder and assuming a well-defined morphology, not
      changing in time.

PMID- 25953334
TI  - Gamma-irradiation of deglycerolized red cells does not significantly affect in
      vitro quality.
AB  - BACKGROUND AND OBJECTIVES: Red cells frozen with glycerol may require gamma
      irradiation after thawing and deglycerolization for transfusion to at-risk
      patients. Both freezing and irradiation are known to cause red cell damage.
      However, the effect of irradiation on the quality of deglycerolized red cells and
      the optimal shelf life of such a component is currently unknown. MATERIALS AND
      METHODS: Red cells (<7 days) were pooled, split and glycerolized using an ACP-215
      automated cell washer (n = 12 pairs) and frozen at -80 degrees C. Red cells were
      thawed, deglycerolized and resuspended in SAG-M. One of each pair was gamma
      irradiated, while the other served as a control. Products were stored at 2-6
      degrees C and sampled for in vitro testing immediately after irradiation, and at
      24 and 48 h postirradiation. RESULTS: Irradiation of deglycerolized red cells led
      to a >1.5-fold increase in extracellular potassium, compared to control units at
      24 and 48 h postirradiation. Other parameters, including haemolysis, were not
      significantly affected by irradiation postdeglycerolization. CONCLUSION:
      Deglycerolized, irradiated red cells had increased supernatant potassium, but
      remained of acceptable quality for 24 h postirradiation.

PMID- 25953335
TI  - Behavioral idiosyncrasy reveals genetic control of phenotypic variability.
AB  - Quantitative genetics has primarily focused on describing genetic effects on
      trait means and largely ignored the effect of alternative alleles on trait
      variability, potentially missing an important axis of genetic variation
      contributing to phenotypic differences among individuals. To study the genetic
      effects on individual-to-individual phenotypic variability (or intragenotypic
      variability), we used Drosophila inbred lines and measured the spontaneous
      locomotor behavior of flies walking individually in Y-shaped mazes, focusing on
      variability in locomotor handedness, an assay optimized to measure variability.
      We discovered that some lines had consistently high levels of intragenotypic
      variability among individuals, whereas lines with low variability behaved as
      although they tossed a coin at each left/right turn decision. We demonstrate that
      the degree of variability is itself heritable. Using a genome-wide association
      study (GWAS) for the degree of intragenotypic variability as the phenotype across
      lines, we identified several genes expressed in the brain that affect variability
      in handedness without affecting the mean. One of these genes, Ten-a, implicates a
      neuropil in the central complex of the fly brain as influencing the magnitude of
      behavioral variability, a brain region involved in sensory integration and
      locomotor coordination. We validated these results using genetic deficiencies,
      null alleles, and inducible RNAi transgenes. Our study reveals the constellation
      of phenotypes that can arise from a single genotype and shows that different
      genetic backgrounds differ dramatically in their propensity for phenotypic
      variabililty. Because traditional mean-focused GWASs ignore the contribution of
      variability to overall phenotypic variation, current methods may miss important
      links between genotype and phenotype. 

PMID- 25953336
TI  - Optogenetic and pharmacological suppression of spatial clusters of face neurons
      reveal their causal role in face gender discrimination.
AB  - Neurons that respond more to images of faces over nonface objects were identified
      in the inferior temporal (IT) cortex of primates three decades ago. Although it
      is hypothesized that perceptual discrimination between faces depends on the
      neural activity of IT subregions enriched with "face neurons," such a causal link
      has not been directly established. Here, using optogenetic and pharmacological
      methods, we reversibly suppressed the neural activity in small subregions of IT
      cortex of macaque monkeys performing a facial gender-discrimination task. Each
      type of intervention independently demonstrated that suppression of IT subregions
      enriched in face neurons induced a contralateral deficit in face gender
      discrimination behavior. The same neural suppression of other IT subregions
      produced no detectable change in behavior. These results establish a causal link
      between the neural activity in IT face neuron subregions and face gender
      discrimination behavior. Also, the demonstration that brief neural suppression of
      specific spatial subregions of IT induces behavioral effects opens the door for
      applying the technical advantages of optogenetics to a systematic attack on the
      causal relationship between IT cortex and high-level visual perception. 

PMID- 25953337
TI  - Neuronal control of locomotor handedness in Drosophila.
AB  - Genetically identical individuals display variability in their physiology,
      morphology, and behaviors, even when reared in essentially identical
      environments, but there is little mechanistic understanding of the basis of such
      variation. Here, we investigated whether Drosophila melanogaster displays
      individual-to-individual variation in locomotor behaviors. We developed a new
      high-throughout platform capable of measuring the exploratory behavior of
      hundreds of individual flies simultaneously. With this approach, we find that,
      during exploratory walking, individual flies exhibit significant bias in their
      left vs. right locomotor choices, with some flies being strongly left biased or
      right biased. This idiosyncrasy was present in all genotypes examined, including
      wild-derived populations and inbred isogenic laboratory strains. The biases of
      individual flies persist for their lifetime and are nonheritable: i.e., mating
      two left-biased individuals does not yield left-biased progeny. This locomotor
      handedness is uncorrelated with other asymmetries, such as the handedness of gut
      twisting, leg-length asymmetry, and wing-folding preference. Using transgenics
      and mutants, we find that the magnitude of locomotor handedness is under the
      control of columnar neurons within the central complex, a brain region implicated
      in motor planning and execution. When these neurons are silenced, exploratory
      laterality increases, with more extreme leftiness and rightiness. This
      observation intriguingly implies that the brain may be able to dynamically
      regulate behavioral individuality. 

PMID- 25953338
TI  - John Schellman and the birth of protein folding.

PMID- 25953339
TI  - Low-grade serous primary peritoneal carcinoma incidentally found in a hernia sac.
AB  - Very rarely, a primary peritoneal serous carcinoma can be observed in a hernia
      sac. We herein describe a low-grade serous primary peritoneal carcinoma
      incidentally found in a postmenopausal woman following examination of the femoral
      hernia repair sac. Our case is significant for its unusual presentation. The
      lesion initially appeared as a 0.3-cm tumor that disseminated in the peritoneum,
      persisted, and progressed for 75 months. The absence of ovarian disease indicated
      a primary peritoneal origin. Tumor cells were immunohistochemically positive for
      PAX8, claudin-4, and VE1, excluding the possibility of being of mesothelial
      origin. Recognition that a low-grade serous primary peritoneal carcinoma can be
      incidentally found in a hernia sac should simplify future diagnoses.
      Immunohistochemistry is helpful in making the correct diagnosis. 

PMID- 25953340
TI  - Clinicopathological study of pulmonary extranodal nature killer/T-cell lymphoma,
      nasal type and literature review.
AB  - OBJECTIVES: Malignant tumors of the lung are predominantly derived from
      epithelial tissue, such as squamous cell carcinoma and adenocarcinoma, while
      pulmonary lymphatic and hematopoietic tumor is relatively rare. Extranodal NK/T
      cell lymphoma (ENKTL), nasal type, originates in nasal and extra-nasal sites
      anatomically. This distinct non-Hodgkin lymphoma is endemic and is characterized
      by a highly aggressive clinical course and dismal survival outcome. Extra-nasal
      ENKTL, especially pulmonary ENKTL, is rare compared with nasal type ENKTL and has
      received relatively little attention. Therefore, this study was conducted to
      assess the clinicopathological features of pulmonary ENKTL and to promote
      awareness of this malignancy. MATERIALS AND METHODS: All cases of ENKTL, nasal
      type diagnosed from January 2008 to June 2014 in our institution were collected,
      and those with pulmonary involvement were selected for further study. The
      eligible cases were analyzed retrospectively: medical recordings, imaging
      manifestations, pathological features, immunophenotypes, EBER1/2 hybridizations
      in situ and other related literatures were reviewed. RESULTS AND CONCLUSIONS: A
      total of 1105 cases were diagnosed as ENKTL, nasal type, in this period, and 8
      cases (7.20/00) had lung involvement. Seven cases had core biopsy, and for 1
      case, a resected tissue specimen was available. The group was composed of 6 men
      and 2 women (gender ratio 3:1) with ages ranging from 19 to 44 (average age of
      33.5) years. In this group, 2 cases were secondary and 5 cases were primary. The
      clinical symptoms and computed tomography (CT) manifestations were nonspecific.
      Histologically, the neoplasms presented angiocentric and angiodestructive growth
      patterns with different degrees of inflammatory response and necrosis. The
      neoplastic cell sizes were heterogeneous with spectra of small to large or mixed
      composition types. For the immunophenotypes, all cases were positive for CD3E and
      cytotoxic granule (granzyme B or TIA-1). The positive ratios of CD56 and CD30
      were 6/8 and 4/5 respectively. All 8 cases showed positive in situ hybridization
      for Epstein-Barr virus-encoded small RNA (EBER). TCR-gamma gene rearrangement was
      tested in 4 cases, and only 1 of these cases was monoclonal. Laboratory testing
      demonstrated that the whole blood was decreased while the average level of LDH
      was elevated. Six bone marrow biopsy specimens were negative and showed no
      neoplastic cells infiltration. For treatment, 4 individuals accepted chemotherapy
      and 1 patient underwent localized tumor resection surgery. The follow-up
      information was available for 6 patients, 1 of whom was alive and the other 5
      cases survived shortly between 20 days and 4 months. ENKTL, nasal type of lung is
      very rare, and the diagnosis is challenging due to nonspecific clinical symptoms
      and imaging results. The diagnosis of pulmonary ENKTL should be based on
      comprehensive clinical, imaging, histopathological and molecular examination.
      More effective treatment strategies are required for this disease.

PMID- 25953341
TI  - Associations between attachment and psychopathology dimensions in a large sample
      of patients with psychosis.
AB  - Attachment theory is a powerful theoretical framework that complements and
      extents current models psychosis. We tested the hypothesis that attachment
      anxiety and avoidance are differentially associated with the severity of
      positive, negative and general psychopathology symptoms in patients with a
      diagnosis of psychosis. Five hundred patients with DSM-IV or ICD-10 diagnoses of
      psychotic disorders (schizophrenia, schizoaffective or non-affective psychosis)
      from independent samples from Netherlands, United Kingdom and Israel completed
      the Relationship Questionnaire. Psychopathology was assessed with the Positive
      and Negative Syndromes Scale. We used both categorical and dimensional approach
      to attachment data, which were analyzed using ANOVA with post-hoc tests,
      Pearson's correlations and multiple regression analysis. The conservative level
      of statistical significance was established (p < 0.001) to control for multiple
      testing. After adjustment for possible confounders, attachment anxiety predicted
      severity of positive symptoms as well as affective symptoms. Both attachment
      anxiety and avoidance were associated with severity of hallucinations and
      persecution Contrary to predictions, attachment avoidance was not associated with
      overall scores for negative symptoms, although there was some evidence of
      relatively weaker association between avoidance and social and emotional
      withdrawal.

PMID- 25953342
TI  - Tilburg frailty indicator. German translation and psychometric testing.
AB  - BACKGROUND: The Tilburg frailty indicator (TFI) is a self-report measurement
      instrument which integrates the physical, psychological and social domains to
      assess frailty in older adults. The aim of this study was the adaptation of the
      TFI to a German version and testing of the psychometric properties. MATERIAL AND
      METHODS: This study surveyed 210 individuals aged 64-91 years living at home. The
      mean age of participants was M = 75.3+/-5.7 years with 62 % females. The internal
      consistency was tested with Cronbach's alpha. The test-retest reliability was
      calculated after 20 weeks. The German TFI was validated using alternative
      measures for assessment of the quality of life, e.g. Eurohis-QoL-8 and short form
      health survey (SF-12), the patient health questionnaire (PHQ), the geriatric
      anxiety inventory short form (GAI-SF), the social support scale (F-Soz-U-K-14)
      and the resilience scale (RS-11). RESULTS: The internal consistency was
      acceptable with a value for Cronbach's alpha of 0.67. The test-retest reliability
      was good after 5 months alpha = 0.87 (physical domain r = 0.85, psychological
      domain r = 0.75 and social domain r = 0.84). The inter-item correlations ranged
      between - 0.06 and 0.57. Correlations with alternative frailty measures showed
      good convergent and divergent validity. CONCLUSION: This study showed acceptable
      psychometric properties of the German adaptation of the TFI which was found to be
      age and frailty sensitive. The results of the validity of the TFI support the
      three domains integrated in the frailty score. Further application and testing of
      the German TFI in primary care and clinical settings are suggested to consolidate
      the findings.

PMID- 25953343
TI  - Gender and age predict outcomes of cognitive, balance and vision testing in a
      multidisciplinary concussion center.
AB  - OBJECTIVE: This study examined components of the Sports Concussion Assessment
      Tool, 3rd Edition (SCAT3) and a vision-based test of rapid number naming (King
      Devick [K-D]) to evaluate sports and non-sports concussion patients in an
      outpatient, multidisciplinary concussion center. While the Symptom Evaluation,
      Standardized Assessment of Concussion (SAC), modified Balance Error Scoring
      System (BESS), and K-D are used typically for sideline assessment, their use in
      an outpatient clinical setting following concussion has not been widely
      investigated. METHODS: K-D, BESS, SAC, and SCAT3 Symptom Evaluation scores were
      analyzed for 206 patients who received concussion care at the Concussion Center
      at NYU Langone Medical Center. Patient age, gender, referral data, mechanism of
      injury, time between concussive event and first concussion center appointment,
      and the first specialty service to evaluate each patient were also analyzed.
      RESULTS: In this cohort, Symptom Evaluation scores showed a higher severity and a
      greater number of symptoms to be associated with older age (r = 0.31, P = 0.002),
      female gender (P = 0.002, t-test), and longer time between the concussion event
      and first appointment at the concussion center (r = 0.34, P = 0.008). Performance
      measures of K-D and BESS also showed associations of worse scores with increasing
      patient age (r = 0.32-0.54, P <= 0.001), but were similar among males and females
      and across the spectrum of duration since the concussion event. Patients with
      greater Symptom Severity Scores also had the greatest numbers of referrals to
      specialty services in the concussion center (r = 0.33, P = 0.0008). Worse
      Immediate Memory scores on SAC testing correlated with slower K-D times,
      potentially implicating the dorsolateral prefrontal cortex as a commonly involved
      brain structure. CONCLUSION: This study demonstrates a novel use of sideline
      concussion assessment tools for evaluation in the outpatient setting, and
      implicates age and gender as predictors of outcomes for these tests.

PMID- 25953345
TI  - Diversity of epithelial morphogenesis during eggshell formation in drosophilids.
AB  - The eggshells of drosophilid species provide a powerful model for studying the
      origins of morphological diversity. The dorsal appendages, or respiratory
      filaments, of these eggshells display a remarkable interspecies variation in
      number and shape, and the epithelial patterning underlying the formation of these
      structures is an area of active research. To extend the analysis of dorsal
      appendage formation to include morphogenesis, we developed an improved 3D image
      reconstruction approach. This approach revealed considerable interspecies
      variation in the cell shape changes and neighbor exchanges underlying appendage
      formation. Specifically, although the appendage floor in Drosophila melanogaster
      is formed through spatially ordered neighbor exchanges, the same structure in
      Scaptodrosophila pattersoni is formed through extreme changes in cell shape,
      whereas Drosophila funebris appears to display a combination of both cellular
      mechanisms. Furthermore, localization patterns of Par3/Bazooka suggest a self
      organized, cell polarity-based origin for the variability of appendage number in
      S. pattersoni. Our results suggest that species deploy different combinations of
      apically and basally driven mechanisms to convert a two-dimensional primordium
      into a three-dimensional structure, and provide new directions for exploring the
      molecular origins of interspecies morphological variation. 

PMID- 25953346
TI  - Phyllotaxis involves auxin drainage through leaf primordia.
AB  - The spatial arrangement of leaves and flowers around the stem, known as
      phyllotaxis, is controlled by an auxin-dependent reiterative mechanism that leads
      to regular spacing of the organs and thereby to remarkably precise phyllotactic
      patterns. The mechanism is based on the active cellular transport of the
      phytohormone auxin by cellular influx and efflux carriers, such as AUX1 and PIN1.
      Their important role in phyllotaxis is evident from mutant phenotypes, but their
      exact roles in space and time are difficult to address due to the strong
      pleiotropic phenotypes of most mutants in phyllotaxis. Models of phyllotaxis
      invoke the accumulation of auxin at leaf initials and removal of auxin through
      their developing vascular strand, the midvein. We have developed a precise
      microsurgical tool to ablate the midvein at high spatial and temporal resolution
      in order to test its function in leaf formation and phyllotaxis. Using amplified
      femtosecond laser pulses, we ablated the internal tissues in young leaf primordia
      of tomato (Solanum lycopersicum) without damaging the overlying L1 and L2 layers.
      Our results show that ablation of the future midvein leads to a transient
      accumulation of auxin in the primordia and to an increase in their width.
      Phyllotaxis was transiently affected after midvein ablations, but readjusted
      after two plastochrons. These results indicate that the developing midvein is
      involved in the basipetal transport of auxin through young primordia, which
      contributes to phyllotactic spacing and stability. 

PMID- 25953347
TI  - The cytoskeleton-associated protein SCHIP1 is involved in axon guidance, and is
      required for piriform cortex and anterior commissure development.
AB  - SCHIP1 is a cytoplasmic partner of cortical cytoskeleton ankyrins. The IQCJ
      SCHIP1 isoform is a component of axon initial segments and nodes of Ranvier of
      mature axons in peripheral and central nervous systems, where it associates with
      membrane complexes comprising cell adhesion molecules. SCHIP1 is also expressed
      in the mouse developing central nervous system during embryonic stages of active
      axonogenesis. Here, we identify a new and early role for SCHIP1 during axon
      development and establishment of the anterior commissure (AC). The AC is composed
      of axons from the piriform cortex, the anterior olfactory nucleus and the
      amygdala. Schip1 mutant mice displayed early defects in AC development that might
      result from impaired axon growth and guidance. In addition, mutant mice presented
      a reduced thickness of the piriform cortex, which affected projection neurons in
      layers 2/3 and was likely to result from cell death rather than from impairment
      of neuron generation or migration. Piriform cortex neurons from E14.5 mutant
      embryos displayed axon initiation/outgrowth delay and guidance defects in vitro.
      The sensitivity of growth cones to semaphorin 3F and Eph receptor B2, two
      repulsive guidance cues crucial for AC development, was increased, providing a
      possible basis for certain fiber tract alterations. Thus, our results reveal new
      evidence for the involvement of cortical cytoskeleton-associated proteins in the
      regulation of axon development and their importance for the formation of neuronal
      circuits. 

PMID- 25953344
TI  - Casz1 is required for cardiomyocyte G1-to-S phase progression during mammalian
      cardiac development.
AB  - Organ growth occurs through the integration of external growth signals during the
      G1 phase of the cell cycle to initiate DNA replication. Although numerous growth
      factor signals have been shown to be required for the proliferation of
      cardiomyocytes, genetic studies have only identified a very limited number of
      transcription factors that act to regulate the entry of cardiomyocytes into S
      phase. Here, we report that the cardiac para-zinc-finger protein CASZ1 is
      expressed in murine cardiomyocytes. Genetic fate mapping with an inducible Casz1
      allele demonstrates that CASZ1-expressing cells give rise to cardiomyocytes in
      the first and second heart fields. We show through the generation of a cardiac
      conditional null mutation that Casz1 is essential for the proliferation of
      cardiomyocytes in both heart fields and that loss of Casz1 leads to a decrease in
      cardiomyocyte cell number. We further report that the loss of Casz1 leads to a
      prolonged or arrested S phase, a decrease in DNA synthesis, an increase in
      phospho-RB and a concomitant decrease in the cardiac mitotic index. Taken
      together, these studies establish a role for CASZ1 in mammalian cardiomyocyte
      cell cycle progression in both the first and second heart fields. 

PMID- 25953348
TI  - DEFECTIVE KERNEL 1 promotes and maintains plant epidermal differentiation.
AB  - During plant epidermal development, many cell types are generated from
      protodermal cells, a process requiring complex co-ordination of cell division,
      growth, endoreduplication and the acquisition of differentiated cellular
      morphologies. Here we show that the Arabidopsis phytocalpain DEFECTIVE KERNEL 1
      (DEK1) promotes the differentiated epidermal state. Plants with reduced DEK1
      activity produce cotyledon epidermis with protodermal characteristics, despite
      showing normal growth and endoreduplication. Furthermore, in non-embryonic
      tissues (true leaves, sepals), DEK1 is required for epidermis differentiation
      maintenance. We show that the HD-ZIP IV family of epidermis-specific
      differentiation-promoting transcription factors are key, albeit indirect, targets
      of DEK1 activity. We propose a model in which DEK1 influences HD-ZIP IV gene
      expression, and thus epidermis differentiation, by promoting cell adhesion and
      communication in the epidermis. 

PMID- 25953351
TI  - One SNP in COLD1 Determines Cold Tolerance during Rice Domestication.

PMID- 25953349
TI  - Understanding upper extremity home programs and the use of gaming technology for
      persons after stroke.
AB  - BACKGROUND: Many persons post-stroke continue to have difficulty using their more
      involved upper extremity and home programs may be poorly adhered to limiting the
      amount of practice an individual receives. More information on the experience of
      traditional home program and the acceptability of a novel home intervention was
      sought. OBJECTIVE: To qualitatively describe 1) upper extremity use at home, 2)
      previous home exercise or activity programs, and 3) the acceptability of a novel
      upper extremity home program, NeuroGame Therapy (NGT), that combines surface
      electromyography (sEMG) biofeedback and a commercial computer game. METHODS: A
      purposeful sample of ten persons with moderate to severe upper extremity motor
      impairment used the NGT intervention in their home for four weeks and completed
      nested (pre and post) one-on-one interviews. Written transcripts from the
      interviews were coded and themes were identified to address stated objectives.
      RESULTS: Participants reported that while use of their upper extremity in daily
      activities was recommended it occurred infrequently. Most participants described
      previous home programs as being non-specific, were often not carried out as
      recommended or were self-modified. Participants found NGT to be engaging and
      motivating, but reported minimal changes in the functional uses of their upper
      extremity. CONCLUSION: These findings suggest that after stroke upper extremity
      use may be infrequent and home program approaches could be re-examined. NGT was
      reported to be an acceptable home intervention, but it will require further
      development and study to understand its value and role in post-stroke
      rehabilitation.

PMID- 25953350
TI  - Profile of energy expenditure in people with rheumatoid arthritis.
AB  - BACKGROUND: No definitive conclusions have been made on the levels of physical
      activity in the rheumatoid arthritis (RA) population. Similarly no clear
      consensus has been reached on the correlates and predictors of physical activity
      in the population. OBJECTIVE: To profile total energy expenditure (TEE), resting
      energy expenditure (REE) and physical activity related energy expenditure (PAEE)
      levels using a validated objective measurement tool and to determine demographic
      and health related factors which influence and predict TEE and PAEE levels in
      individuals with RA. METHODS: Fifty nine (41 female, 18 male) individuals with RA
      were recruited to this cross sectional study. Energy expenditure was measured
      over seven days using SenseWear Armband. Correlational analysis and logistic
      regression were used to examine the relationship between demographic and health
      related factors and TEE, REE and PAEE. RESULTS: A profile of energy expenditure
      in RA individuals was developed in terms of levels, differences between genders
      and differences between weekdays and weekend days. Median TEE, PAEE and REE were
      2204.0, 409.5 and 1506.2 kcal/day respectively. Energy expenditure was associated
      with factors such as gender, age, body mass index, employment status, disease
      severity and smoking. CONCLUSION: The findings add to the growing research
      assessing energy expenditure in the RA population and strengthen the position due
      to the use of an objective validated tool. Some recommendations on what factors
      are associated with energy expenditure in the RA population are made, thus
      unveiling ways to tailor physical activity type interventions in this group.

PMID- 25953352
TI  - A Toolkit of CRISPR-Based Genome Editing Systems in Drosophila.
AB  - The last couple of years have witnessed an explosion in development of CRISPR
      based genome editing technologies in cell lines as well as in model organisms. In
      this review, we focus on the applications of this popular system in Drosophila.
      We discuss the effectiveness of the CRISPR/Cas9 systems in terms of delivery,
      mutagenesis detection, parameters affecting efficiency, and off-target issues,
      with an emphasis on how to apply this powerful tool to characterize gene
      functions. 

PMID- 25953353
TI  - The Performance of Whole Genome Amplification Methods and Next-Generation
      Sequencing for Pre-Implantation Genetic Diagnosis of Chromosomal Abnormalities.
AB  - Reliable and accurate pre-implantation genetic diagnosis (PGD) of patient's
      embryos by next-generation sequencing (NGS) is dependent on efficient whole
      genome amplification (WGA) of a representative biopsy sample. However, the
      performance of the current state of the art WGA methods has not been evaluated
      for sequencing. Using low template DNA (15 pg) and single cells, we showed that
      the two PCR-based WGA systems SurePlex and MALBAC are superior to the REPLI-g WGA
      multiple displacement amplification (MDA) system in terms of consistent and
      reproducible genome coverage and sequence bias across the 24 chromosomes,
      allowing better normalization of test to reference sequencing data. When copy
      number variation sequencing (CNV-Seq) was applied to single cell WGA products
      derived by either SurePlex or MALBAC amplification, we showed that known disease
      CNVs in the range of 3-15 Mb could be reliably and accurately detected at the
      correct genomic positions. These findings indicate that our CNV-Seq pipeline
      incorporating either SurePlex or MALBAC as the key initial WGA step is a powerful
      methodology for clinical PGD to identify euploid embryos in a patient's cohort
      for uterine transplantation.

PMID- 25953354
TI  - SCAB3 Is Required for Reorganization of Actin Filaments during Light Quality
      Changes.
AB  - The stomatal closure-related actin binding protein (SCAB) family is plant
      specific, and its members all contain a novel actin binding domain. Here, we
      report that SCAB3, a homolog of SCAB1, binds, stabilizes and bundles actin
      filaments. The SCAB3 promoter contains a cis-element which could be bound by the
      FHY3/FAR1 transcription factors. Consistently, the expression of SCAB3 is induced
      when plants were transferred from white light to far red light (T-Far Red)
      conditions. The scab3 mutants show defects in the control of hypocotyl elongation
      under T-Far Red condition, which may result from an impaired reorganization of
      actin filaments. Together, our results suggest that SCAB3 plays an important role
      in plant growth under changes of light conditions possibly by regulating actin
      filament dynamics.

PMID- 25953355
TI  - Mitochondrial DNA as a risk factor for false positives in case-control
      association studies.

PMID- 25953356
TI  - A Positive Correlation between Elevated Altitude and Frequency of Mutant Alleles
      at the EPAS1 and HBB Loci in Chinese Indigenous Dogs.

PMID- 25953357
TI  - Role of GABA Deficit in Sensitivity to the Psychotomimetic Effects of
      Amphetamine.
AB  - Some schizophrenia patients are more sensitive to amphetamine (AMPH)-induced
      exacerbations in psychosis-an effect that correlates with higher striatal
      dopamine release. This enhanced vulnerability may be related to gamma
      aminobutyric acid (GABA) deficits observed in schizophrenia. We hypothesized that
      a pharmacologically induced GABA deficit would create vulnerability to the
      psychotomimetic effects to the 'subthreshold' dose of AMPH in healthy subjects,
      which by itself would not induce clinically significant increase in positive
      symptoms. To test this hypothesis, a GABA deficit was induced by intravenous
      infusion of iomazenil (IOM; 3.7 MUg/kg), an antagonist and partial inverse
      agonist of benzodiazepine receptor. A subthreshold dose of AMPH (0.1 mg/kg) was
      administered by intravenous infusion. Healthy subjects received placebo IOM
      followed by placebo AMPH, active IOM followed by placebo AMPH, placebo IOM
      followed by active AMPH, and active IOM followed by active AMPH in a randomized,
      double-blind crossover design over 4 test days. Twelve healthy subjects who had a
      subclinical response to active AMPH alone were included in the analysis.
      Psychotomimetic effects (Positive and Negative Syndrome Scale (PANSS)),
      perceptual alterations (Clinician Administered Dissociative Symptoms Scale
      (CADSS)), and subjective effects (visual analog scale) were captured before and
      after the administration of drugs. IOM significantly augmented AMPH-induced peak
      changes in PANSS positive symptom subscale and both subjective and objective
      CADSS scores. There were no pharmacokinetic interactions. In conclusion, GABA
      deficits increased vulnerability to amphetamine-induced psychosis-relevant
      effects in healthy subjects, suggesting that pre-existing GABA deficits may
      explain why a subgroup of schizophrenia patients are vulnerable to AMPH. 

PMID- 25953358
TI  - Differential Involvement of the Agranular vs Granular Insular Cortex in the
      Acquisition and Performance of Choice Behavior in a Rodent Gambling Task.
AB  - Substance-related and addictive disorders, in particular gambling disorder, are
      known to be associated with risky decision-making behavior. Several neuroimaging
      studies have identified the involvement of the insular cortex in decision-making
      under risk. However, the extent of this involvement remains unclear and the
      specific contributions of two distinct insular subregions, the rostral agranular
      (RAIC) and the caudal granular (CGIC), have yet to be examined. Animals were
      trained to perform a rat gambling task (rGT), in which subjects chose between
      four options that differed in the magnitude and probability of rewards and
      penalties. In order to address the roles of the RAIC and CGIC in established
      choice behavior, pharmacological inactivations of these two subregions via local
      infusions of GABA receptor agonists were performed following 30 rGT training
      sessions. The contribution made by the RAIC or CGIC to the acquisition of choice
      behavior was also determined by lesioning these areas before behavioral training.
      Inactivation of the RAIC, but not of the CGIC, shifted rats' preference toward
      options with greater reward frequency and lower punishment. Before rGT
      acquisition, lesions of the RAIC, but not the CGIC, likewise resulted in a higher
      preference for options with greater reward frequency and lower punishment, and
      this persisted throughout the 30 training sessions. Our results provide
      confirmation of the involvement of the RAIC in rGT choice behavior and suggest
      that the RAIC may mediate detrimental risky decision-making behavior, such as
      that associated with addiction and gambling disorder. 

PMID- 25953359
TI  - Functional Uncoupling NMDAR NR2A Subunit from PSD-95 in the Prefrontal Cortex:
      Effects on Behavioral Dysfunction and Parvalbumin Loss after Early-Life Stress.
AB  - Exposure to early-life stress increases vulnerability to psychiatric disorders,
      including depression, schizophrenia, and anxiety. Growing evidence implicates
      aberrant development of the prefrontal cortex (PFC) in the effects of early-life
      stress, which often emerge in adolescence or young adulthood. Specifically, early
      life stress in the form of maternal separation (MS) in rodents has been shown to
      decrease parvalbumin (PVB)-positive interneurons in the adolescent PFC; however,
      the mechanism underpinning behavioral dysfunction and PVB loss is not yet known.
      We recently reported that MS causes overexpression of the NMDA subunit NR2A in
      the PFC of adolescent rats. Elevated PFC NR2A is also found in developmental
      models of schizophrenia and is correlated with behavioral deficits, acting
      largely through its association with the postsynaptic protein PSD-95. In
      addition, adolescent maturation of PVB-positive interneurons relies on NR2A
      driven NMDA activity. Therefore, it is possible that the NR2A/PSD-95 signaling
      complex has a role in adolescent MS effects. Here, we aimed to determine whether
      a discrete manipulation of PFC NR2A could prevent MS effects on PFC-controlled
      behaviors, including cognition, anxiety, and novelty-induced hyperlocomotion, as
      well as PVB loss in adolescence. We intracranially infused the NR2A-specific
      blocking peptide TAT2A in order to uncouple NR2A from PSD-95 in the early
      adolescent PFC, without antagonizing the NMDA receptor. We demonstrated that MS
      rats treated with TAT2A during early adolescence were protected from MS-induced
      PVB loss and exhibited less anxious behavior than those infused with control
      peptide. These data implicate NR2A-related N-methyl-D-aspartate receptor
      development in adolescent behavioral and neural consequences of early-life
      stress. 

PMID- 25953360
TI  - Alcohol-Seeking Triggered by Discrete Pavlovian Cues is Invigorated by Alcohol
      Contexts and Mediated by Glutamate Signaling in the Basolateral Amygdala.
AB  - The environmental context in which a discrete Pavlovian conditioned stimulus (CS)
      is experienced can profoundly impact conditioned responding elicited by the CS.
      We hypothesized that alcohol-seeking behavior elicited by a discrete CS that
      predicted alcohol would be influenced by context and require glutamate signaling
      in the basolateral amygdala (BLA). Male, Long-Evans rats were allowed to drink
      15% ethanol (v/v) until consumption stabilized. Next, rats received Pavlovian
      conditioning sessions in which a 10 s CS (15 trials/session) was paired with
      ethanol (0.2 ml/CS). Entries into a port where ethanol was delivered were
      measured. Pavlovian conditioning occurred in a specific context (alcohol context)
      and was alternated with sessions in a different context (non-alcohol context)
      where neither the CS nor ethanol was presented. At test, the CS was presented
      without ethanol in the alcohol context or the non-alcohol context, following a
      bilateral microinfusion (0.3 MUl/hemisphere) of saline or the AMPA glutamate
      receptor antagonist NBQX (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline
      7-sulfonamide disodium salt) in the BLA (0, 0.3, or 1.0 MUg/0.3 MUl). The effect
      of NBQX (0, 0.3 MUg/0.3 MUl) in the caudate putamen (CPu) on CS responding in the
      non-alcohol context was also tested. The discrete alcohol CS triggered more
      alcohol-seeking behavior in the alcohol context than the non-alcohol context.
      NBQX in the BLA reduced CS responding in both contexts but had no effect in the
      CPu. These data indicate that AMPA glutamate receptors in the BLA are critical
      for alcohol-seeking elicited by a discrete CS and that behavior triggered by the
      CS is strongly invigorated by an alcohol context. 

PMID- 25953361
TI  - Intervention of rAAV-hTERT-Transducted Nucleus Pulposus Cells in Early Stage of
      Intervertebral Disc Degeneration: A Study in Canine Model.
AB  - OBJECTIVES: To investigate the efficacy of recombinant adeno-associated virus
      (rAAV)-human telomerase reverse transcriptase (hTERT)-transducted nucleus
      pulposus cells (NPCs) in disc degeneration process in a canine disc degeneration
      model. METHODS: The intervertebral disc degeneration of lumbar (L) 1-2, L3-4, and
      L5-6, from 12 female mongrels was prepared with the 20-gauge biopsy gun. Four
      weeks after animal model preparation, intervention experiment with rAAV-hTERT
      transducted NPCs was conducted: group A, L1-2, serum-free medium with rAAV-hTERT
      modified NPCs; group B, L3-4, serum-free medium with NPCs; group C, L5-6, serum
      free medium alone. Canines underwent digital radiography and magnetic resonance
      imaging 1 day before intervention, and 4, 8, and 12 weeks after intervention to
      evaluate the change of disc height and hydration status of interventional
      intervertebral discs. Twelve weeks after intervention, histological,
      biomechanical, and biochemical studies were carried out. RESULTS: The rAAV-hTERT
      transducted NPCs were constructed successfully. The mRNA level of hTERT from rAAV
      hTERT-transfected NPCs increased obviously. There was no significant change of
      disc height index observed between groups and within groups. The relative
      grayscale index (RGI) was maintained 8 weeks after the intervention in group A,
      whereas in group B and group C, the RGI decreased significantly (p<0.05). No
      significant differences of the angle of lateral bending and extension-flexion
      bending were observed in group A compared with other groups (p>0.05). The
      morphology of disc structure was preserved in group A. In group B, the structure
      of inner annulus was broken down and the jelly-like nucleus pulposus (NP) tissue
      transmitted into the fibrocartilaginous tissue. In group C, the jelly-like NP
      tissue was completely replaced by fibrocartilaginous tissue. In the NP, the
      content of proteoglycan (PG) and collagen II was higher in group A than in group
      C (p<0.05). The content of PG was 13, 8.9, and 15.6 times higher than the content
      of collagen II in group A, group B, and group C, respectively. CONCLUSIONS: In 12
      weeks of observation, rAAV-hTERT-transducted NPCs could delay the degeneration
      process in the canine model which was superior than the capacity of NPCs in
      preserving structure integrity, content of extracellular matrix, and mechanical
      stability.

PMID- 25953362
TI  - Biotic ligand modeling approach: Synthesis of the effect of major cations on the
      toxicity of metals to soil and aquatic organisms.
AB  - The biotic ligand model (BLM) approach is used to assess metal toxicity, taking
      into account the competition of other cations with the free metal ions for
      binding to the biotic ligand sites of aquatic and soil organisms. The
      bioavailable fraction of metals, represented by the free metal ion, is a better
      measure than the total concentration for assessing their potential risk to the
      environment. Because BLMs are relating toxicity to the fraction of biotic ligands
      occupied by the metal, they can be useful for investigating factors affecting
      metal bioaccumulation and toxicity. In the present review, the effects of major
      cations on the toxicity of metals to soil and aquatic organisms were
      comprehensively studied by performing a meta-analysis of BLM literature data.
      Interactions at the binding sites were shown to be species- and metal-specific.
      The main factors affecting the relationships between toxicity and conditional
      binding constants for metal binding at the biotic ligand appeared to be Ca(2+) ,
      Mg(2+) , and protons. Other important characteristics of the exposure medium,
      such as levels of dissolved organic carbon and concentrations of other cations,
      should also be considered to obtain a proper assessment of metal toxicity to soil
      and aquatic organisms.

PMID- 25953364
TI  - Stroke literature synopses: basic science.

PMID- 25953363
TI  - The pharmacokinetics and safety of darapladib in subjects with severe renal
      impairment.
AB  - AIM: Darapladib is a potent and reversible orally active inhibitor of lipoprotein
      associated phospholipase A2 (Lp-PLA2 ). The aim of the study was to assess the
      effects of severe renal impairment on the pharmacokinetics and
      safety/tolerability of darapladib compared with normal renal function. METHODS:
      This was an open label, parallel group study of darapladib following 10 day once
      daily 160 mg oral dosing in subjects with normal (n = 8) and severe renal
      impairment (estimated glomerular filtration rate <30 ml min(-1) 1.73 m(-2) , n =
      8). Plasma concentrations of total and unbound darapladib as well as total
      darapladib metabolites were determined in samples obtained over 24 h on day 10.
      RESULTS: Plasma concentrations of total and unbound darapladib as well as all
      three metabolites were higher in subjects with severe renal impairment. Area
      under the plasma concentration vs. time curve between time zero and 24 h
      (AUC(0,24 h) and maximum plasma concentration (Cmax ) of total darapladib in
      severely renally impaired subjects were 52% and 59% higher than those in the
      matched healthy subjects, respectively. Similar results were found with the
      darapladib metabolites. Darapladib was highly plasma protein bound with 0.047%
      and 0.034% unbound circulating in plasma in severely renally impaired and healthy
      subjects, respectively. Unbound plasma darapladib exposures were more than two
      fold higher in severely renally impaired subjects than in healthy controls.
      Adverse events (AE) were reported in 38% of healthy subjects and 75% of severely
      renally impaired subjects, most of which were mild or moderate in intensity.
      CONCLUSIONS: The results of this study showed that darapladib exposure was
      increased in subjects with severe renal impairment compared with healthy
      controls. However, darapladib was generally well tolerated in both groups.

PMID- 25953365
TI  - Multicontrast high-resolution vessel wall magnetic resonance imaging and its
      value in differentiating intracranial vasculopathic processes.
AB  - BACKGROUND AND PURPOSE: Although studies have attempted to differentiate
      intracranial vascular disease using vessel wall magnetic resonance imaging (VWI),
      none have incorporated multicontrast imaging. This study uses T1- and T2-weighted
      VWI to differentiate intracranial vasculopathies. METHODS: We retrospectively
      reviewed patients with clinically defined intracranial vasculopathies causing
      luminal stenosis/irregularity who underwent VWI studies. Two blinded experts
      evaluated T1 precontrast and postcontrast and T2-weighted VWI characteristics,
      including the pattern of wall thickening; presence, pattern, and intensity of
      postcontrast enhancement; and T2 signal characteristics. RESULTS: Twenty-one
      cases of atherosclerosis (intracranial atherosclerotic disease [ICAD]), 4 of
      reversible cerebral vasoconstriction syndrome, and 4 of vasculitis were
      identified, with a total of 118 stenotic lesions (81 ICAD, 22 reversible cerebral
      vasoconstriction syndrome, and 15 vasculitic lesions). There was substantial to
      excellent inter-reader agreement for the assessment of lesional T2 hyperintensity
      (kappa=0.80), pattern of wall thickening (kappa=0.87), presence (kappa=0.90),
      pattern (kappa=0.73), and intensity (kappa=0.77) of enhancement. ICAD lesions
      were significantly more likely to have eccentric wall involvement (90.1%) than
      reversible cerebral vasoconstriction syndrome (8.2%; P<0.001) and vasculitic
      lesions (6.7%; P<0.001) and were also more likely to have T2 hyperintensity
      present than the other 2 vasculopathies (79% versus 0%; P<0.001). There were also
      significant differences in the presence, intensity, and pattern of enhancement
      between all lesion types. Combining T1 and T2 VWI increased the sensitivity of
      VWI in differentiating ICAD from other vasculopathies from 90.1% to 96.3%.
      CONCLUSIONS: Multicontrast VWI can be a complementary tool for intracranial
      vasculopathy differentiation, which often leads to more invasive workups when
      reversible cerebral vasoconstriction syndrome and vasculitis are in the
      differential diagnosis.

PMID- 25953366
TI  - Methodological Factors in Determining Risk of Dementia After Transient Ischemic
      Attack and Stroke: (II) Effect of Attrition on Follow-Up.
AB  - BACKGROUND AND PURPOSE: Cognitive outcomes in cohorts and trials are often based
      only on face-to-face clinic assessment. However, cognitive impairment is strongly
      associated with increased morbidity and mortality, leading to substantial loss to
      clinic follow-up. In the absence of previous population-based data, we determined
      the effect of such attrition on measured risk of dementia after transient
      ischemic attack and stroke. METHODS: Patients with transient ischemic attack or
      stroke prospectively recruited (2002-2007) into the Oxford Vascular (OXVASC)
      study had baseline clinical/cognitive assessment and follow-up to 2014. Dementia
      was diagnosed through face-to-face clinic interview, supplemented by home visits
      and telephone assessment in patients unable to attend clinic and by hand
      searching of primary care records in uncontactable patients. RESULTS: Of 1236
      patients (mean age/SD, 75.2/12.1 years; 582 men), 527 (43%) died by 5-year follow
      up. Follow-up assessment rates (study clinic, home visit, or telephone) of
      survivors were 947 in 1026 (92%), 857 in 958 (89%), 792 in 915 (87%), and 567 in
      673 (84%) at 1, 6, 12 months and 5 years. Dementia developed in 260 patients, of
      whom 110 (42%; n=50 primary care records, n=49 home visit, and n=11 telephone
      follow-up) had not been available for face-to-face clinic follow-up at the time
      of diagnosis. The 5-year cumulative incidence of postevent dementia was 29% (26%
      32%) overall but was only 17% (14% to 19%) in clinic assessed versus 45% (39%
      51%) in nonclinic-assessed patients (P difference<0.001). CONCLUSIONS: Exclusion
      of patients unavailable for clinic follow-up reduces the measured risk of
      postevent dementia. Use of multiple follow-up methods, including home visits,
      telephone assessments, and consent, to access primary care records substantially
      increases ascertainment of longer-term dementia outcomes.

PMID- 25953368
TI  - Racial/Ethnic variation in carotid artery revascularization utilization and
      outcomes: analysis from the National Cardiovascular Data Registry.
AB  - BACKGROUND AND PURPOSE: It is not known whether racial or ethnic disparities
      observed with other revascularization procedures are also seen with carotid
      artery stenting (CAS) and endarterectomy (CEA). METHODS: We compared the
      utilization and outcomes of CAS and CEA across racial/ethnic groups within the
      CARE Registry between May 2007 and December 2012. RESULTS: Between 2007 and 2012,
      of the 13 129 patients who underwent CAS, majority were non-Hispanic whites
      (89.3%), followed by blacks (4.4%), Hispanics (4.3%), and other groups (2.0%). A
      similar distribution was observed among the 10 953 patients undergoing CEA (non
      Hispanic whites, 92.6%; blacks, 3.5%; Hispanics, 2.8%; and other groups, 1.1%).
      During this time period, a trend toward proportionate increase in CAS utilization
      was observed in non-Hispanic whites and other groups, whereas the opposite was
      observed among Hispanics and blacks. This trend persisted even when hospitals
      performing both CAS and CEA were exclusively analyzed. Adherence to antiplatelet
      and statin therapy was significantly lower among blacks post CEA. In-hospital
      major adverse cardiac and cerebrovascular events remained comparable across
      groups post CAS and CEA. At 30 days, the incidence of stroke (7.2%) and major
      adverse cardiac and cerebrovascular events (8.8%) was higher among blacks post
      CEA (P<0.05), after risk adjustment. CONCLUSION: During the study period,
      utilization of CAS and CEA was highest among non-Hispanic whites. There was a
      trend toward increased CAS utilization over time among non-Hispanic whites and
      other groups, and a trend toward increased CEA utilization among Hispanics and
      blacks. In-hospital major adverse cardiac and cerebrovascular events remained
      comparable between groups, whereas 30-day major adverse cardiac and
      cerebrovascular events were significantly higher in blacks.

PMID- 25953367
TI  - Common NOTCH3 Variants and Cerebral Small-Vessel Disease.
AB  - BACKGROUND AND PURPOSE: The most common monogenic cause of cerebral small-vessel
      disease is cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy, caused by NOTCH3 gene mutations. It has been hypothesized
      that more common variants in NOTCH3 may also contribute to the risk of sporadic
      small-vessel disease. Previously, 4 common variants (rs10404382, rs1043994,
      rs10423702, and rs1043997) were found to be associated with the presence of white
      matter hyperintensity in hypertensive community-dwelling elderly. METHODS: We
      investigated the association of common single nucleotide polymorphisms (SNPs) in
      NOTCH3 in 1350 patients with MRI-confirmed lacunar stroke and 7397 controls, by
      meta-analysis of genome-wide association study data sets. In addition, we
      investigated the association of common SNPs in NOTCH3 with MRI white matter
      hyperintensity volumes in 3670 white patients with ischemic stroke. In each
      analysis, we considered all SNPs within the NOTCH3 gene, and within 50-kb
      upstream and downstream of the coding region. A total of 381 SNPs from the 1000
      genome population with a mean allele frequency>0.01 were included in the
      analysis. A significance level of P<0.0015 was used, adjusted for the effective
      number of independent SNPs in the region using the Galwey method. RESULTS: We
      found no association of any common variants in NOTCH3 (including rs10404382,
      rs1043994, rs10423702, and rs1043997) with lacunar stroke or white matter
      hyperintensity volume. We repeated our analysis stratified for hypertension but
      again found no association. CONCLUSIONS: Our study does not support a role for
      common NOTCH3 variation in the risk of sporadic small-vessel disease.

PMID- 25953369
TI  - Is blood pressure control for stroke prevention the correct goal? The lost
      opportunity of preventing hypertension.
AB  - BACKGROUND AND PURPOSE: Although pharmacological treatment of hypertension has
      important health benefits, it does not capture the benefit of maintenance of
      ideal health through the prevention or delay of hypertension. METHODS: A total of
      26 875 black and white participants aged 45+ years were assessed and followed for
      incident stroke events. The association was assessed between incident stroke and:
      (1) systolic blood pressure (SBP)categorized as normal (<120 mm Hg),
      prehypertension (120-139 mm Hg), stage 1 hypertension (140-159 mm Hg), and stage
      2 hypertension (160 mm Hg+), and (2) number of classes of antihypertensive
      medications, classified as none, 1, 2, or 3 or more. RESULTS: During 6.3 years of
      follow-up, 823 stroke events occurred. Nearly half (46%) of the population were
      successfully treated (SBP<140 mm Hg) hypertensives. Within blood pressure strata,
      the risk of stroke increased with each additional class of required
      antihypertensive medication, with hazard ratio [HR], 1.33; 95% confidence
      interval, 1.16 to 1.52 for normotensive, HR, 1.15; 95% confidence interval, 1.05
      to 1.26 for prehypertension, and HR, 1.22; 95% confidence interval, 1.06 to 1.39
      for stage 1 hypertension. A successfully treated (SBP<120 mm Hg) hypertensive
      person on 3+ antihypertensive medication classes was at marginally higher stroke
      risk than a person with untreated stage 1 hypertension (HR, 2.48 versus HR=2.19;
      relative to those with SBP <120 on no antihypertensive medications). CONCLUSIONS:
      Maintaining the normotensive status solely through pharmacological treatment has
      a profound impact, as nearly half of this general population cohort were treated
      to guideline (SBP<140 mm Hg) but failed to return to risk levels similar to
      normotensive individuals. Even with successful treatment, there is a substantial
      potential gain by prevention or delay of hypertension.

PMID- 25953370
TI  - Functional and motor outcome 5 years after stroke is equivalent to outcome at 2
      months: follow-up of the collaborative evaluation of rehabilitation in stroke
      across Europe.
AB  - BACKGROUND AND PURPOSE: Recovery of patients within the first 6 months after
      stroke is well documented, but there has been little research on long-term
      recovery. The aim of this study was to analyze functional and motor recovery
      between admission to rehabilitation centres and 5 years after stroke. METHODS:
      This follow-up of the Collaborative Evaluation of Rehabilitation in Stroke Across
      Europe study, included patients from 4 European rehabilitation centres. Patients
      were assessed on admission, at 2 and 6 months, and 5 years after stroke, using
      the Barthel Index, Rivermead Motor Assessment Gross Function, Leg and Trunk
      function, and Arm function. Linear mixed models were used, corrected for baseline
      characteristics. To account for the drop-out during follow-up, the analysis is
      likelihood-based (assumption of missingness at random). RESULTS: A total of 532
      patients were included in this study, of which 238 were followed up at 5 years
      post stroke. Mean age at stroke onset was 69 (+/-10 SD) years, 53% were men, 84%
      had ischemic strokes, and 53% had left-sided motor impairment. Linear mixed model
      analysis revealed a significant deterioration for all 4 outcomes between 6 months
      and 5 years (P<0.0001). Scores at 2 months were not statistically significant
      different from scores at 5 years after stroke. Higher age (P<0.0001) and
      increasing stroke severity on admission (P<0.0001) negatively affected long-term
      functional and motor recovery. CONCLUSIONS: Five-year follow-up revealed
      deterioration in functional and motor outcome, with a return to the level
      measured at 2 months. Increasing age and increasing stroke severity negatively
      affected recovery up to 5 years after stroke.

PMID- 25953371
TI  - Molecular mechanisms of skeletal muscle atrophy in a mouse model of cerebral
      ischemia.
AB  - BACKGROUND AND PURPOSE: Loss of muscle mass and function is a severe complication
      in patients with stroke that contributes to promoting physical inactivity and
      disability. The deleterious consequences of skeletal muscle mass loss underline
      the necessity to identity the molecular mechanisms involved in skeletal muscle
      atrophy after cerebral ischemia. METHODS: Transient focal cerebral ischemia (60
      minutes) was induced by occlusion of the right middle cerebral artery in C57BL/6J
      male mice. Skeletal muscles were removed 3 days later and analyzed for the
      regulation of critical determinants of muscle mass homeostasis (Akt/mammalian
      target of rapamycin pathway, myostatin-Smad2/3 and bone morphogenetic protein
      Smad1/5/8 signaling pathways, ubiquitin-proteasome and autophagy-lysosome
      proteolytic pathways). RESULTS: Cerebral ischemia induced severe sensorimotor
      deficits associated with muscle mass loss of the paretic limbs. Mechanistically,
      cerebral ischemia repressed Akt/mammalian target of rapamycin pathway and
      increased expression of key players of ubiquitin-proteasome pathway (MuRF1
      [muscle RING finger-1], MAFbx [muscle atrophy F-box], Musa1 [muscle ubiquitin
      ligase of SCF complex in atrophy-1]), together with a marked increase in
      myostatin expression, in both paretic and nonparetic skeletal muscles. The
      Smad1/5/8 pathway was also activated. CONCLUSIONS: Our data fit with a model in
      which a repression of Akt/mammalian target of rapamycin pathway and an increase
      in the expression of key players of ubiquitin-proteasome pathway are critically
      involved in skeletal muscle atrophy after cerebral ischemia. Cerebral ischemia
      also caused an activation of bone morphogenetic protein-Smad1/5/8 signaling
      pathway, suggesting that compensatory mechanisms are also concomitantly activated
      to limit the extent of skeletal muscle atrophy.

PMID- 25953372
TI  - Contribution of convexal subarachnoid hemorrhage to disease progression in
      cerebral amyloid angiopathy.
AB  - BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy-related cortical superficial
      siderosis (cSS) seems to indicate an increased risk of subsequent intracerebral
      hemorrhage (ICH). We wanted to identify the mechanisms and sequence of
      hemorrhagic events which are responsible for this association. METHODS: During a
      9-year-period, we identified patients with spontaneous convexal subarachnoid
      hemorrhage (cSAH) and performed a careful longitudinal analysis of clinical and
      neuroimaging data. A close imaging-histopathologic correlation was performed in
      one patient. RESULTS: Of 38 cSAH patients (mean age, 77+/-11 years), 29 (76%) had
      imaging features of cerebral amyloid angiopathy on baseline magnetic resonance
      imaging. Twenty-six (68%) had cSS. Sixteen subjects underwent postcontrast
      magnetic resonance imaging. Extravasation of gadolinium at the site of the acute
      cSAH was seen on all postcontrast scans. After a mean of 24+/-22 (range 1-78)
      months of follow-up, 15 (39%) had experienced recurrent cSAHs and 14 (37%) had
      suffered lobar ICHs. Of 22 new ICHs, 17 occurred at sites of previous cSAHs or
      cSS. Repeated neuroimaging showed expansion of cSAH into the brain parenchyma and
      evolution of a lobar ICH in 4 patients. Propagation of cSS was observed in 21
      (55%) patients, with 14 of those having experienced recurrent cSAHs. In the
      autopsy case, leakage of meningeal vessels affected by cerebral amyloid
      angiopathy was noted. CONCLUSIONS: In cerebral amyloid angiopathy, leakage of
      meningeal vessels seems to be a major cause for recurrent intrasulcal bleedings,
      which lead to the propagation of cSS and indicate sites with increased
      vulnerability for future ICH. Intracerebral bleedings may also develop directly
      from or in extension of a cSAH.

PMID- 25953373
TI  - What is missing from my missing data plan?

PMID- 25953374
TI  - Relative Influence of Capillary Index Score, Revascularization, and Time on
      Stroke Outcomes From the Interventional Management of Stroke III Trial.
AB  - BACKGROUND AND PURPOSE: Until recently, acute ischemic stroke (AIS) trials have
      failed to show a benefit of endovascular therapy compared with standard therapy,
      leading some authors to recommend decreasing the time from ictus to
      revascularization to improve outcomes. We hypothesize that improving patient
      selection using the capillary index score (CIS) may also be a useful strategy.
      METHODS: CIS was calculated, blinded to outcome, from pretreatment diagnostic
      cerebral angiograms for 78 subjects in the Interventional Management of Stroke
      III database with internal carotid artery and middle cerebral artery trunk
      occlusion. The CIS was dichotomized into favorable (fCIS=2 or 3) and poor (pCIS=0
      or 1). Outcomes were categorized based on the modified Rankin Scale score at 90
      days (0-2 considered a good outcome). Modified thrombolysis in cerebral
      infarction score 2b or 3 was considered good revascularization. Multivariable
      logistic regression was performed to relate CIS, time from ictus to
      revascularization, modified thrombolysis in cerebral infarction score, and
      National Institue of Health Stroke Scale score to good outcomes. RESULTS: Only
      CIS and modified thrombolysis in cerebral infarction scores were correlated with
      good outcomes (P<0.01). Patients with fCIS and good revascularization achieved
      71% modified Rankin Scale<=2, compared with 13% for patients with pCIS and good
      revascularization. CONCLUSIONS: In this subset of patients from the
      Interventional Management of Stroke III Trial, CIS and modified thrombolysis in
      cerebral infarction were strong predictors of outcome after endovascular
      reperfusion. Using the CIS to improve patient selection could be a powerful
      strategy to improve rate of good outcomes in endovascular therapy. A randomized
      trial is needed. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT00359424.

PMID- 25953376
TI  - Role of anesthesia for endovascular treatment of ischemic stroke: do we need
      neurophysiological monitoring?

PMID- 25953375
TI  - Ratio of Apolipoprotein A-II/B Improves Risk Prediction of Postoperative Survival
      After Carotid Endarterectomy.
AB  - BACKGROUND AND PURPOSE: Even in patients with high-grade carotid stenosis,
      cardiovascular morbidity causes more deaths than strokes do. Despite successful
      low-density lipoprotein (LDL) cholesterol lowering, a significant risk of
      atherosclerotic cardiovascular disease remains, eventually rendering other lipid
      or lipoprotein ratios more efficient treatment targets. This study aimed to
      investigate the predictive value of the ratio of serum apolipoprotein A-II/B for
      overall mortality (primary outcome) of carotid surgery patients. METHODS: This
      single-center, nonrandomized, prospective cohort study comprised 327 consecutive
      patients undergoing carotid endarterectomy for high-grade internal carotid artery
      stenosis. Baseline lipoprotein concentrations were measured, and patients were
      observed for the occurrence of the primary outcome until the census date
      (January, 2003 to January, 2012; median follow-up, 102.3 months). RESULTS: The
      ratio of apolipoprotein A-II/B (hazard ratio, 0.74 per SD; confidence interval,
      0.60-0.91; P=0.004) showed the highest association with the primary outcome
      compared with other lipid-risk parameters, significantly improving a prognostic
      model based on major cardiovascular risk factors, including LDL, high-density
      lipoprotein, and triglycerides in terms of overall performance, calibration, and
      discrimination. This led to a significantly improved reclassification of 8.9% of
      all patients (net reclassification improvement, 0.137; P=0.006 and integrated
      discrimination improvement, 0.041; P<0.001) and of 13.6% of patients with a serum
      baseline concentration of <100 mg/dL LDL (net reclassification improvement,
      0.270; P=0.030 and integrated discrimination improvement, 0.061; P=0.002).
      CONCLUSIONS: Apolipoprotein A-II/B significantly improves risk prediction of
      overall survival, also in carotid surgery patients with lower LDL levels.
      Consequently, this ratio might provide an efficient diagnostic tool and
      eventually a treatment target for actual lipid-lowering therapies, which has to
      be addressed in future randomized controlled trials.

PMID- 25953377
TI  - [Adolescents and young adults with cancer between adaptation and addiction: state
      of the question].
AB  - The purpose of this literature review is to make a point on the state of health
      of adolescents and young adults (15-25 years) suffering from cancer. The
      adaptation strategies and the impact of the announcement of cancer will be
      discussed. In addition, we are going to consider the characteristics of teenagers
      and young adults, given the fact that development is still in progress. This
      period is especially punctuated by various experiments and the emergence of some
      clinical signs. Also, we have identified various studies concerning the use of
      licit and illicit substances. Furthermore, we have taken interest in behavioral
      addictions, particularly cyber addiction. While trying to cross these variables
      with a population of teenagers and young adults in the context of somatic
      diseases, it occurred that this population was not well known and studied. The
      interest of this synthesis is to underline the importance to make future
      researches in these perspectives.

PMID- 25953378
TI  - Cardiovascular risk markers in patients with psoriatic arthritis: A meta-analysis
      of literature studies.
AB  - INTRODUCTION: Several studies reported an increased cardiovascular (CV) morbidity
      and mortality in patients with psoriatic arthritis (PsA). We performed a meta
      analysis on the impact of PsA on major markers of CV risk. METHODS: Studies on
      the relationship between PsA and common carotid artery intima-media thickness
      (CCA-IMT), prevalence of carotid plaques, flow-mediated dilation (FMD), nitrate
      mediated dilation (NMD), pulse wave velocity (PWV), augmentation index (AIx), and
      ankle-brachial index (ABI) were systematically searched in the PubMed, Web of
      Science, Scopus, and EMBASE databases. RESULTS: Sixteen case-control studies (898
      cases, 1,140 controls) were included. Compared to controls, PsA patients showed a
      higher CCA-IMT (MD 0.07 mm; 95% CI 0.04, 0.11; P < 0.0001), and a higher
      frequency of carotid plaques (OR 3.12; 95% CI 1.03, 9.39; P = 0.04). Moreover, a
      lower FMD was found in PsA subjects than in controls (MD -2.56%; 95% CI -4.17, 
      0.94; P = 0.002), with no differences in NMD (MD -0.40%; 95% CI -1.19, 0.39; P =
      0.32). Because of the low number of studies, no meta- analytical evaluation was
      performed for PWV, AIx, and ABI. Despite heterogeneity among studies, PsA appears
      significantly associated with markers of subclinical atherosclerosis and CV risk.
      DISCUSSION: These findings could help to establish more specific CV prevention
      strategies in this clinical setting.

PMID- 25953380
TI  - Impact and management of chemotherapy/radiotherapy-induced nausea and vomiting
      and the perceptual gap between oncologists/oncology nurses and patients: a cross
      sectional multinational survey.
AB  - PURPOSE: Chemotherapy/radiotherapy-induced nausea and vomiting (CINV/RINV) can
      affect half of oncology patients, significantly impacting daily life. Nausea
      without vomiting has only recently been thought of as a condition in its own
      right. As such, the incidence of nausea is often underestimated. This survey
      investigated the incidence and impact of CINV/RINV in patients compared with
      estimations of physicians/oncology nurses to determine if there is a perceptual
      gap between healthcare professionals and patients. METHODS: An online research
      survey of physicians, oncology nurses and patients was conducted across five
      European countries. Participants had to have experience prescribing/recommending
      or have received anti-emetic medication for CINV/RINV treatment. Questionnaires
      assessed the incidence and impact of CINV/RINV, anti-emetic usage and compliance,
      and attribute importance of anti-emetic medication. RESULTS: A total of 947 (375
      physicians, 186 oncology nurses and 386 patients) participated in this survey.
      The incidence of nausea was greater than vomiting: 60 % of patients reported
      nausea alone, whereas 18 % reported vomiting. Physicians and oncology nurses
      overestimated the incidence of CINV/RINV but underestimated its impact on
      patients' daily lives. Only 38 % of patients reported full compliance with
      physicians'/oncology nurses' guidelines when self-administering anti-emetic
      medication. Leading factors for poor compliance included reluctance to add to a
      pill burden and fear that swallowing itself would induce nausea/vomiting.
      CONCLUSIONS: There is a perceptual gap between healthcare professionals and
      patients in terms of the incidence and impact of CINV/RINV. This may lead to sub
      optimal prescription of anti-emetics and therefore management of CINV/RINV.
      Minimising the pill burden and eliminating the requirement to swallow medication
      could improve poor patient compliance with anti-emetic regimens.

PMID- 25953379
TI  - Connecting by breaking and repairing: mechanisms of DNA strand exchange in
      meiotic recombination.
AB  - During prophase of meiosis I, homologous chromosomes interact and undergo
      recombination. Successful completion of these processes is required in order for
      the homologous chromosomes to mount the meiotic spindle as a pair. The
      organization of the chromosomes into pairs ensures orderly segregation to
      opposite poles of the dividing cell, such that each gamete receives one copy of
      each chromosome. Chiasmata, the cytological manifestation of crossover products
      of recombination, physically connect the homologs in pairs, providing a linkage
      that facilitates their segregation. Consequently, mutations that reduce the level
      of recombination are invariably associated with increased errors in meiotic
      chromosome segregation. In this review, we focus on recent biochemical and
      genetic advances in elucidating the mechanisms of meiotic DNA strand exchange
      catalyzed by the Dmc1 protein. We also discuss the mode by which two
      recombination mediators, Hop2 and Mnd1, facilitate rate-limiting steps of DNA
      strand exchange catalyzed by Dmc1.

PMID- 25953381
TI  - An interdisciplinary palliative rehabilitation intervention bolstering general
      self-efficacy to attenuate symptoms of depression in patients living with
      advanced cancer.
AB  - PURPOSE: Patients with advanced cancer, post-anticancer treatment, are living
      longer than 10-20 years ago. This emerging population of survivors has unique
      palliative and rehabilitation needs. A particular concern is depression, which
      can impair functioning, quality of life, and survival. The interdisciplinary
      Palliative Rehabilitation Program offers holistic palliative rehabilitation for
      this population using a self-efficacy framework. The current study examined the
      unique impact of three program factors that have been shown to improve
      depression: inflammation, exercise, and self-efficacy. METHOD: Patients underwent
      a 2-month interdisciplinary intervention (up to six disciplines) and thorough pre
      post assessments. Measures included serum C-reactive protein, 6-min walk test,
      General Self-efficacy Scale, and Hospital Anxiety and Depression Scale
      (depression subscale). Paired t tests analyzed pre-post changes in each variable,
      and a hierarchical linear regression analyzed the predictors' unique
      contributions of changes in depression in this quasi-experimental design.
      RESULTS: The sample included 80 patients (52.5% females), with stages 3/4
      heterogeneous cancers. Results revealed that C-reactive protein (CRP) did not
      significantly change pre-post, from 7.39 (SD = 11.99) to 9.47 mg/L (SD = 16.41),
      p = 0.110, exercise significantly increased, from 372.55 (SD = 137.71) to 412.64
      m (SD = 144.31), p < 0.001, self-efficacy significantly increased from 27.86 (SD
      = 6.16) to 31.23 units (SD = 5.77), p < 0.001, and depression scores
      significantly decreased, from 7.14 (SD = 3.91) to 5.95 units (SD = 3.51), p =
      0.002. A hierarchical linear regression revealed that this model explained 15% of
      variance in changes in depression scores, p = 0.006. Change in self-efficacy
      accounted for 11% of change in depression scores (p < 0.001). Change in CRP and
      exercise did not make a significant contribution. CONCLUSIONS: A self-efficacy
      framework may be a helpful ingredient in interdisciplinary intervention to
      decrease depressive symptomatology.

PMID- 25953382
TI  - Heterogeneity in fibromyalgia based upon cognitive and physical performance and
      psychological symptomology.
AB  - PURPOSE: This study sought to investigate the existence of subgroups within a
      fibromyalgia (FM) sample based on physical and cognitive performance measures, as
      well as self-report psychological measures. A multisystem disorder characterized
      by widespread musculoskeletal pain and co-morbid conditions, FM can lead to
      declines in cognitive functioning and difficulty with psychological health. DATA
      SOURCES: Community participants (n = 57 women) recruited from support groups and
      university center databases provided documentation of having met the criteria for
      diagnosis of FM. Measures included validated performance and self-report
      instruments. Analysis was completed using hierarchical cluster analysis; a four
      cluster solution was chosen for its level of interpretability. The resulting
      model identified four distinct subgroups based upon patterns of performance and
      symptomology. Significant group differences were found on pain, fatigue,
      stiffness, and level of physical activity. CONCLUSIONS: Study results support the
      existence of subgroups among the FM population based on levels of cognitive and
      physical performance and psychological symptoms. IMPLICATIONS FOR PRACTICE: Nurse
      practitioners aware of potential subgroups within FM should be better prepared to
      recommend treatment options for patients that target subgroup characteristics
      (e.g., high vs. low levels of psychological symptoms).

PMID- 25953383
TI  - Long-Term Clinical Outcomes and Survivorship of Revision Total Knee Arthroplasty
      with Use of a Constrained Condylar Knee Prosthesis.
AB  - The purpose of this study was to determine long-term clinical and radiographic
      results. One hundred and ninety-four patients (228 knees) underwent revision TKA
      with use of a constrained condylar knee prosthesis. The mean duration of follow
      up was 14.6 years (range, 11 to 16 years). The mean pre-revision Knee Society
      knee scores (43.5 points) and function scores (47.0 points), and Western Ontario
      and McMaster Universities Osteoarthritis index scores (88 points) were improved
      significantly (P=0.002) to 85.6, 68.5, and 25 points, respectively, at 14.6 years
      follow-up. Eighteen knees (8%) had re-revision. Four knees were re-revised for
      infection. Kaplan-Meier survivorship analysis revealed that the 16-year rate of
      survival of the components was 94.7% as the end point of loosening and 92% as the
      end point of revision.

PMID- 25953384
TI  - Hydrogen peroxide room disinfection--ready for prime time?
AB  - Non-manual techniques for terminal disinfection of hospital rooms have gained
      increasing interest in recent years as means to reduce transmission of multidrug
      resistant organisms (MDROs). A prospective crossover study by Blazejewski and
      colleagues in five ICUs of a French academic hospital with a high prevalence of
      MDRO carriers showed that two different hydrogen peroxide (H2O2)-based non-touch
      disinfection techniques reduced environmental contamination with MDROs after
      routine cleaning. This study provides further evidence of the 'in use' bioburden
      reduction offered by these techniques. Before H2O2-based non-touch disinfection
      can be recommended for routine clinical use outside specific outbreak situations,
      further studies need to show whether the environmental contamination reduction
      provided by these techniques is clinically relevant and results in reduced cross
      infections with MDROs. 

PMID- 25953385
TI  - Erratum: a complex intervention to improve pregnancy outcome in obese women; the
      UPBEAT randomised controlled trial.

PMID- 25953387
TI  - Factors influencing the outdoor concentration of carbonaceous aerosols at urban
      schools in Brisbane, Australia: Implications for children's exposure.
AB  - This comprehensive study aimed to determine the sources and driving factors of
      organic carbon (OC) and elemental carbon (EC) concentrations in ambient PM2.5 in
      urban schools. Sampling was conducted outdoors at 25 schools in the Brisbane
      Metropolitan Area, Australia. Concentrations of primary and secondary OC were
      quantified using the EC tracer method, with secondary OC accounting for an
      average of 60%. Principal component analysis distinguished the contributing
      sources above the background and identified groups of schools with differing
      levels of primary and secondary carbonaceous aerosols. Overall, the results
      showed that vehicle emissions, local weather conditions and secondary organic
      aerosols (SOA) were the key factors influencing concentrations of carbonaceous
      component of PM2.5 at these schools. These results provide insights into
      children's exposure to vehicle emissions and SOA at such urban schools. 

PMID- 25953386
TI  - Relationship between surfactant proteins B and C and obstructive sleep apnea: is
      serum SP-B concentration a potential biomarker of obstructive sleep apnea?
AB  - BACKGROUND: Surfactant proteins B and C are mainly synthesized, secreted by
      alveolar type II cells, and affected by hypoxia and mechanical stretches. We
      hypothesized that their serum levels might be altered by intermittent hypoxia and
      swing of intrathoracic pressure of obstructive sleep apnea (OSA). METHODS:
      Consecutive 140 middle-aged males, suspicious of OSA determined by
      polysomnography, were studied. Surfactant proteins B and C were determined by
      ELISA. RESULTS: Surfactant protein B (41.39 +/- 6.01 vs 44.73 +/- 7.62 ng/L, p =
      0.005), not C (32.60 +/- 6.00 vs 32.43 +/- 6.44 ng/L, p = 0.61), significantly
      lowered in moderate to severe OSA subjects than in non to mild OSA subjects.
      Severity of OSA is inversely correlated with serum surfactant protein B.
      Adjusting age, body mass index, and smoking history, compared to subjects with
      surfactant protein B (SP-B) >=43.35 ng/L, those with SP-B <43.35 ng/L showed
      significantly increased 1.528-fold risk for moderate to severe OSA (p = 0.009),
      whereas no association between surfactant protein C and OSA was observed.
      Prevalence of moderate to severe OSA in lower SP-B group is higher than that in
      higher SP-B group (62.7 vs 38.4 %, p = 0.003). Serial and parallel tests on
      Epworth sleep scale (ESS) and SP-B evaluation can be complementary and prove
      helpful with high specificity (94.44 %) and sensitivity (84.48 %) to detect
      moderate to severe OSA. CONCLUSIONS: Serum surfactant protein B, rather than C,
      is decreased in some individuals with moderate to severe OSA, compared to non to
      mild OSA subjects. Serum surfactant protein B might be a potential biomarker to
      diagnose OSA.

PMID- 25953388
TI  - Games among relatives revisited.
AB  - We present a simple model for the evolution of social behavior in family
      structured, finite sized populations. Interactions are represented as
      evolutionary games describing frequency-dependent selection. Individuals interact
      more frequently with siblings than with members of the general population, as
      quantified by an assortment parameter r, which can be interpreted as
      "relatedness". Other models, mostly of spatially structured populations, have
      shown that assortment can promote the evolution of cooperation by facilitating
      interaction between cooperators, but this effect depends on the details of the
      evolutionary process. For our model, we find that sibling assortment promotes
      cooperation in stringent social dilemmas such as the Prisoner's Dilemma, but not
      necessarily in other situations. These results are obtained through
      straightforward calculations of changes in gene frequency. We also analyze our
      model using inclusive fitness. We find that the quantity of inclusive fitness
      does not exist for general games. For special games, where inclusive fitness
      exists, it provides less information than the straightforward analysis.

PMID- 25953389
TI  - Dynamic simulation and modeling of the motion modes produced during the 3D
      controlled manipulation of biological micro/nanoparticles based on the AFM.
AB  - Determining the motion modes and the exact position of a particle displaced
      during the manipulation process is of special importance. This issue becomes even
      more important when the studied particles are biological micro/nanoparticles and
      the goals of manipulation are the transfer of these particles within body cells,
      repair of cancerous cells and the delivery of medication to damaged cells.
      However, due to the delicate nature of biological nanoparticles and their higher
      vulnerability, by obtaining the necessary force of manipulation for the
      considered motion mode, we can prevent the sample from interlocking with or
      sticking to the substrate because of applying a weak force or avoid damaging the
      sample due to the exertion of excessive force. In this paper, the dynamic
      behaviors and the motion modes of biological micro/nanoparticles such as DNA,
      yeast, platelet and bacteria due to the 3D manipulation effect have been
      investigated. Since the above nanoparticles generally have a cylindrical shape,
      the cylindrical contact models have been employed in an attempt to more precisely
      model the forces exerted on the nanoparticle during the manipulation process.
      Also, this investigation has performed a comprehensive modeling and simulation of
      all the possible motion modes in 3D manipulation by taking into account the
      eccentricity of the applied load on the biological nanoparticle. The obtained
      results indicate that unlike the macroscopic scale, the sliding of nanoparticle
      on substrate in nano-scale takes place sooner than the other motion modes and
      that the spinning about the vertical and transverse axes and the rolling of
      nanoparticle occur later than the other motion modes. The simulation results also
      indicate that the applied force necessary for the onset of nanoparticle movement
      and the resulting motion mode depend on the size and aspect ratio of the
      nanoparticle. 

PMID- 25953390
TI  - Stratification of HPV-induced cervical pathology using the virally encoded
      molecular marker E4 in combination with p16 or MCM.
AB  - High-risk human papillomavirus (HPV) types cause cervical lesions of varying
      severity, ranging from transient productive infections to high-grade neoplasia.
      Disease stratification requires the examination of lesional pathology, and
      possibly also the detection of biomarkers. P16(INK4a) and MCM are established
      surrogates of high-risk HPV E6/E7 activity, and can be extensively expressed in
      high-grade lesions. Here we have combined these two cellular biomarkers with
      detection of the abundant HPV-encoded E4 protein in order to identify both
      productive and transforming lesions. This approach has allowed us to distinguish
      true papillomavirus infections from similar pathologies, and has allowed us to
      divide the heterogeneous CIN2 category into those that are CIN1-like and express
      E4, and those that more closely resemble nonproductive CIN3. To achieve this, 530
      lesional areas were evaluated according to standard pathology criteria and by
      using a multiple staining approach that allows us to superimpose biomarker
      patterns either singly or in combination onto an annotated hematoxylin and eosin
      (H&E) image. Conventional grading of neoplasia was established by review panel,
      and compared directly with the composite molecular pathology visualized on the
      same tissue section. The detection of E4 coincided with the onset of vacuolation,
      becoming abundant in koilocytes as the MCM marker declined and cells lost their
      defined nuclear margins as visualized by standard H&E staining. Of the dual
      marker approaches, p16(INK4a) and E4 appeared most promising, with E4 generally
      identifying areas of low-grade disease even when p16(INK4a) was present.
      Extensive p16(INK4a) expression usually coincided with an absence of E4
      expression or its focal retention in sporadic cells within the lesion. Our
      results suggest that a straightforward molecular evaluation of HPV life-cycle
      deregulation in cervical neoplasia may help improve disease stratification, and
      that this can be achieved using complementary molecular biomarker pairs such as
      MCM/E4 or, more promisingly, p16(INK4a)/E4 as an adjunct to conventional
      pathology. 

PMID- 25953391
TI  - Del(20q) in patients with chronic lymphocytic leukemia: a therapy-related
      abnormality involving lymphoid or myeloid cells.
AB  - Deletion 20q (Del(20q)), a common cytogenetic abnormality in myeloid neoplasms,
      is rare in chronic lymphocytic leukemia. We report 64 patients with chronic
      lymphocytic leukemia and del(20q), as the sole abnormality in 40, a stemline
      abnormality in 21, and a secondary abnormality in 3 cases. Fluorescence in situ
      hybridization (FISH) analysis revealed an additional high-risk abnormality,
      del(11q) or del(17p), in 25/64 (39%) cases. In most cases, the leukemic cells
      showed atypical cytologic features, unmutated IGHV (immunoglobulin heavy-chain
      variable region) genes, and ZAP70 positivity. The del(20q) was detected only
      after chemotherapy in all 27 cases with initial karyotypes available. With a
      median follow-up of 90 months, 30 patients (47%) died, most as a direct
      consequence of chronic lymphocytic leukemia. Eight patients developed a therapy
      related myeloid neoplasm, seven with a complex karyotype. Combined morphologic
      and FISH analysis for del(20q) performed in 12 cases without morphologic evidence
      of a myeloid neoplasm localized the del(20q) to the chronic lymphocytic leukemia
      cells in 5 (42%) cases, and to myeloid/erythroid cells in 7 (58)% cases. The
      del(20q) was detected in myeloid cells in all 4 cases of myelodysplastic
      syndrome. In aggregate, these data indicate that chronic lymphocytic leukemia
      with del(20q) acquired after therapy is heterogeneous. In cases with morphologic
      evidence of dysplasia, the del(20q) likely resides in the myeloid lineage.
      However, in cases without morphologic evidence of dysplasia, the del(20q) may
      represent clonal evolution and disease progression. Combining morphologic
      analysis with FISH for del(20q) or performing FISH on immunomagnetically selected
      sub-populations to localize the cell population with this abnormality may help
      guide patient management. 

PMID- 25953392
TI  - A Review of the Current Status of Relevant Zoonotic Pathogens in Wild Swine (Sus
      scrofa) Populations: Changes Modulating the Risk of Transmission to Humans.
AB  - Many wild swine populations in different parts of the World have experienced an
      unprecedented demographic explosion that may result in increased exposure of
      humans to wild swine zoonotic pathogens. Interactions between humans and wild
      swine leading to pathogen transmission could come from different ways, being
      hunters and game professionals the most exposed to acquiring infections from wild
      swine. However, increasing human settlements in semi-natural areas, outdoor
      activities, socio-economic changes and food habits may increase the rate of
      exposure to wild swine zoonotic pathogens and to potentially emerging pathogens
      from wild swine. Frequent and increasing contact rate between humans and wild
      swine points to an increasing chance of zoonotic pathogens arising from wild
      swine to be transmitted to humans. Whether this frequent contact could lead to
      new zoonotic pathogens emerging from wild swine to cause human epidemics or
      emerging disease outbreaks is difficult to predict, and assessment should be
      based on thorough epidemiologic surveillance. Additionally, several gaps in
      knowledge on wild swine global population dynamics trends and wild swine-zoonotic
      pathogen interactions should be addressed to correctly assess the potential role
      of wild swine in the emergence of diseases in humans. In this work, viruses such
      as hepatitis E virus, Japanese encephalitis virus, Influenza virus and Nipah
      virus, and bacteria such as Salmonella spp., Shiga toxin-producing Escherichia
      coli, Campylobacter spp. and Leptospira spp. have been identified as the most
      prone to be transmitted from wild swine to humans on the basis of geographic
      spread in wild swine populations worldwide, pathogen circulation rates in wild
      swine populations, wild swine population trends in endemic areas, susceptibility
      of humans to infection, transmissibility from wild swine to humans and existing
      evidence of wild swine-human transmission events.

PMID- 25953393
TI  - Characterization and functional analysis of a B3 domain factor from Zea mays.
AB  - In this study, we isolated a full-length cDNA and named ZmBDF from zea mays.
      ZmBDF encoded a protein of 356 amino acids and phylogenetic analysis showed that
      it belongs to a closely related subgroup with B3 domain factors in plants. The
      transcript level of ZmBDF could be induced by ABA, MeJA, salt or drought
      treatments. To further investigated the function of ZmBDF, ZmBDF over-expression
      transgenic lines were got by transforming it into Arabidopsis thaliana. ZmBDF
      over-expression transgenic plants in Arabidopsis could increase drought and salt
      tolerant in germination assay. Under drought condition, net photosynthetic rates
      (PN), stomatal conductance (gs), and internal leaf CO2 concentration (Ci) were
      less affected in transgenic plants compared with wild type. Besides, the
      chlorophyll a and chlorophyll b (chl a/chl b) ratio decreased in WT plants than
      the transgenic plants and total carotenoid content show opposite trends.
      Moreover, transgenic plants could also reduce the stomatal density and changed
      the stomatal shape. Taken together, our data suggested that ZmBDF could improve
      stress tolerance to drought and salt in maize. 

PMID- 25953394
TI  - Summary of major conclusions from the 6th International Workshop on Genotoxicity
      Testing (IWGT), Foz do Iguacu, Brazil.

PMID- 25953395
TI  - Critical issues with the in vivo comet assay: A report of the comet assay working
      group in the 6th International Workshop on Genotoxicity Testing (IWGT).
AB  - As a part of the 6th IWGT, an expert working group on the comet assay evaluated
      critical topics related to the use of the in vivo comet assay in regulatory
      genotoxicity testing. The areas covered were: identification of the domain of
      applicability and regulatory acceptance, identification of critical parameters of
      the protocol and attempts to standardize the assay, experience with combination
      and integration with other in vivo studies, demonstration of laboratory
      proficiency, sensitivity and power of the protocol used, use of different
      tissues, freezing of samples, and choice of appropriate measures of cytotoxicity.
      The standard protocol detects various types of DNA lesions but it does not detect
      all types of DNA damage. Modifications of the standard protocol may be used to
      detect additional types of specific DNA damage (e.g., cross-links, bulky adducts,
      oxidized bases). In addition, the working group identified critical parameters
      that should be carefully controlled and described in detail in every published
      study protocol. In vivo comet assay results are more reliable if they were
      obtained in laboratories that have demonstrated proficiency. This includes
      demonstration of adequate response to vehicle controls and an adequate response
      to a positive control for each tissue being examined. There was a general
      agreement that freezing of samples is an option but more data are needed in order
      to establish generally accepted protocols. With regard to tissue toxicity, the
      working group concluded that cytotoxicity could be a confounder of comet results.
      It is recommended to look at multiple parameters such as histopathological
      observations, organ-specific clinical chemistry as well as indicators of tissue
      inflammation to decide whether compound-specific toxicity might influence the
      result. The expert working group concluded that the alkaline in vivo comet assay
      is a mature test for the evaluation of genotoxicity and can be recommended to
      regulatory agencies for use. 

PMID- 25953396
TI  - Recommended protocols for the liver micronucleus test: Report of the IWGT working
      group.
AB  - At the 6th International Workshop on Genotoxicity Testing (IWGT), the liver
      micronucleus test working group discussed practical aspects of the in vivo rodent
      liver micronucleus test (LMNT). The group members focused on the three
      methodologies currently used, i.e., a partial hepatectomy (PH) method, a
      juvenile/young rat (JR) method, and a repeated-dose (RD) method in adult rodents.
      Since the liver is the main organ that metabolizes chemicals, the LMNT is
      expected to detect clastogens, especially those that need metabolic activation in
      the liver, and aneugens. Based on current data the three methods seem to have a
      high sensitivity and specificity, but more data, especially on non-genotoxic but
      toxic substances, would be needed to fully evaluate the test performance. The
      three methods can be combined with the micronucleus test (MNT) using bone marrow
      (BM) and/or peripheral blood (PB). The ability of the PH method to detect both
      clastogens and aneugens has already been established, but the methodology is
      technically challenging. The JR method is relatively straightforward, but animal
      metabolism might not be fully comparable to adult animals, and data on aneugens
      are limited. These two methods also have the advantage of a short testing period.
      The RD method is also straightforward and can be integrated into repeated-dose
      (e.g. 2 or 4 weeks) toxicity studies, but again data on aneugens are limited. The
      working group concluded that the LMNT could be used as a second in vivo test when
      a relevant positive result in in vitro mammalian cell genotoxicity tests is noted
      (especially under the condition of metabolic activation), and a negative result
      is observed in the in vivo BM/PB-MNT. The group members discussed LMNT protocols
      and reached consensus about many aspects of test procedures. However, data gaps
      as mentioned above remain, and further data are needed to fully establish the
      LMNT protocol. 

PMID- 25953397
TI  - Micronucleus test in rodent tissues other than liver or erythrocytes: Report of
      the IWGT working group.
AB  - At the 6th International Workshop on Genotoxicity Testing, the liver micronucleus
      test (MNT) working group briefly discussed the MNT using tissues other than
      liver/erythrocytes. Many tissues other than liver/erythrocytes have been studied,
      primarily for research purposes. They have included the colon and intestinal
      epithelium, skin, spleen, lung, stomach, bladder, buccal mucosa, vagina, and
      fetal/neonatal tissues. These tissues were chosen because they were target sites
      of carcinogens, and/or relevant to a specific route of exposure. Recently, there
      has been particular focus on the gastrointestinal (GI) tract as it is a contact
      site associated with high exposure following oral gavage. Furthermore GI tumors
      are observed with high frequency in human populations. A collaborative study of
      the rat glandular stomach and colon MNT was conducted in conjunction with a
      collaborative study of the repeated-dose liver MNT. Based on limited data
      currently available, the rodent MNT using the glandular stomach and/or colon
      seems to detect genotoxic carcinogens with GI tract target-organ specificity. The
      working group concluded that the GI tract MNT would be a promising method to
      examine clastogenicity or aneugenicity of test chemicals in the stomach and/or
      colon. Further data will be needed to fully establish the methods, and to
      identify the sensitivity and specificity of the GI tract MNT. 

PMID- 25953398
TI  - The in vivo Pig-a assay: A report of the International Workshop On Genotoxicity
      Testing (IWGT) Workgroup.
AB  - The in vivo Pig-a assay uses flow cytometry to measure phenotypic variants for
      antibody binding to cell surface glycosylphosphatidylinositol (GPI)-anchored
      proteins. There is good evidence suggesting that the absence of antibody binding
      is the result of a mutation in the endogenous X-linked Pig-a gene, which forms
      the rationale for the assay. Although the assay has been performed with several
      types of hematopoietic cells and in a variety of mammalian species, including
      humans, currently it is optimized only for measuring CD59-deficient (presumed Pig
      a mutant) erythrocytes in the peripheral blood of rats. An expert workgroup
      formed by the International Workshop on Genotoxicity Testing considered the state
      of assay development and the potential of the assay for regulatory use. Consensus
      was reached on what is known about the Pig-a assay and how it should be
      conducted, and recommendations were made on additional data and refinements that
      would help to further enhance the assay for use in hazard identification and risk
      assessment. 

PMID- 25953399
TI  - Approaches for identifying germ cell mutagens: Report of the 2013 IWGT workshop
      on germ cell assays(?).
AB  - This workshop reviewed the current science to inform and recommend the best
      evidence-based approaches on the use of germ cell genotoxicity tests. The
      workshop questions and key outcomes were as follows. (1) Do genotoxicity and
      mutagenicity assays in somatic cells predict germ cell effects? Limited data
      suggest that somatic cell tests detect most germ cell mutagens, but there are
      strong concerns that dictate caution in drawing conclusions. (2) Should germ cell
      tests be done, and when? If there is evidence that a chemical or its
      metabolite(s) will not reach target germ cells or gonadal tissue, it is not
      necessary to conduct germ cell tests, notwithstanding somatic outcomes. However,
      it was recommended that negative somatic cell mutagens with clear evidence for
      gonadal exposure and evidence of toxicity in germ cells could be considered for
      germ cell mutagenicity testing. For somatic mutagens that are known to reach the
      gonadal compartments and expose germ cells, the chemical could be assumed to be a
      germ cell mutagen without further testing. Nevertheless, germ cell mutagenicity
      testing would be needed for quantitative risk assessment. (3) What new assays
      should be implemented and how? There is an immediate need for research on the
      application of whole genome sequencing in heritable mutation analysis in humans
      and animals, and integration of germ cell assays with somatic cell genotoxicity
      tests. Focus should be on environmental exposures that can cause de novo
      mutations, particularly newly recognized types of genomic changes. Mutational
      events, which may occur by exposure of germ cells during embryonic development,
      should also be investigated. Finally, where there are indications of germ cell
      toxicity in repeat dose or reproductive toxicology tests, consideration should be
      given to leveraging those studies to inform of possible germ cell genotoxicity. 

PMID- 25953401
TI  - IWGT report on quantitative approaches to genotoxicity risk assessment II. Use of
      point-of-departure (PoD) metrics in defining acceptable exposure limits and
      assessing human risk.
AB  - This is the second of two reports from the International Workshops on
      Genotoxicity Testing (IWGT) Working Group on Quantitative Approaches to Genetic
      Toxicology Risk Assessment (the QWG). The first report summarized the discussions
      and recommendations of the QWG related to the need for quantitative dose-response
      analysis of genetic toxicology data, the existence and appropriate evaluation of
      threshold responses, and methods to analyze exposure-response relationships and
      derive points of departure (PoDs) from which acceptable exposure levels could be
      determined. This report summarizes the QWG discussions and recommendations
      regarding appropriate approaches to evaluate exposure-related risks of genotoxic
      damage, including extrapolation below identified PoDs and across test systems and
      species. Recommendations include the selection of appropriate genetic endpoints
      and target tissues, uncertainty factors and extrapolation methods to be
      considered, the importance and use of information on mode of action,
      toxicokinetics, metabolism, and exposure biomarkers when using quantitative
      exposure-response data to determine acceptable exposure levels in human
      populations or to assess the risk associated with known or anticipated exposures.
      The empirical relationship between genetic damage (mutation and chromosomal
      aberration) and cancer in animal models was also examined. It was concluded that
      there is a general correlation between cancer induction and mutagenic and/or
      clastogenic damage for agents thought to act via a genotoxic mechanism, but that
      the correlation is limited due to an inadequate number of cases in which mutation
      and cancer can be compared at a sufficient number of doses in the same target
      tissues of the same species and strain exposed under directly comparable routes
      and experimental protocols. 

PMID- 25953400
TI  - IWGT report on quantitative approaches to genotoxicity risk assessment I. Methods
      and metrics for defining exposure-response relationships and points of departure
      (PoDs).
AB  - This report summarizes the discussion, conclusions, and points of consensus of
      the IWGT Working Group on Quantitative Approaches to Genetic Toxicology Risk
      Assessment (QWG) based on a meeting in Foz do Iguacu, Brazil October 31-November
      2, 2013. Topics addressed included (1) the need for quantitative dose-response
      analysis, (2) methods to analyze exposure-response relationships & derive point
      of departure (PoD) metrics, (3) points of departure (PoD) and mechanistic
      threshold considerations, (4) approaches to define exposure-related risks, (5)
      empirical relationships between genetic damage (mutation) and cancer, and (6)
      extrapolations across test systems and species. This report discusses the first
      three of these topics and a companion report discusses the latter three. The
      working group critically examined methods for determining point of departure
      metrics (PoDs) that could be used to estimate low-dose risk of genetic damage and
      from which extrapolation to acceptable exposure levels could be made using
      appropriate mode of action information and uncertainty factors. These included
      benchmark doses (BMDs) derived from fitting families of exponential models, the
      No Observed Genotoxic Effect Level (NOGEL), and "threshold" or breakpoint dose
      (BPD) levels derived from bilinear models when mechanistic data supported this
      approach. The QWG recognizes that scientific evidence suggests that thresholds
      below which genotoxic effects do not occur likely exist for both DNA-reactive and
      DNA-nonreactive substances, but notes that small increments of the spontaneous
      level cannot be unequivocally excluded either by experimental measurement or by
      mathematical modeling. Therefore, rather than debating the theoretical
      possibility of such low-dose effects, emphasis should be placed on determination
      of PoDs from which acceptable exposure levels can be determined by extrapolation
      using available mechanistic information and appropriate uncertainty factors. This
      approach places the focus on minimization of the genotoxic risk, which protects
      against the risk of the development of diseases resulting from the genetic
      damage. Based on analysis of the strengths and weaknesses of each method, the QWG
      concluded that the order of preference of PoD metrics is the statistical lower
      bound on the BMD > the NOGEL > a statistical lower bound on the BPD. A companion
      report discusses the use of these metrics in genotoxicity risk assessment,
      including scaling and uncertainty factors to be considered when extrapolating
      below the PoD and/or across test systems and to the human.

PMID- 25953402
TI  - Realization of a service for the long-term risk assessment of diabetes-related
      complications.
AB  - AIM: We present a computerized system for the assessment of the long-term risk of
      developing diabetes-related complications. METHODS: The core of the system
      consists of a set of predictive models, developed through a data-mining/machine
      learning approach, which are able to evaluate individual patient profiles and
      provide personalized risk assessments. Missing data is a common issue in
      (electronic) patient records, thus the models are paired with a module for the
      intelligent management of missing information. RESULTS: The system has been
      deployed and made publicly available as Web service, and it has been fully
      integrated within the diabetes-management platform developed by the European
      project REACTION. Preliminary usability tests showed that the clinicians judged
      the models useful for risk assessment and for communicating the risk to the
      patient. Furthermore, the system performs as well as the United Kingdom
      Prospective Diabetes Study (UKPDS) Risk Engine when both systems are tested on an
      independent cohort of UK diabetes patients. CONCLUSIONS: Our work provides a
      working example of risk-stratification tool that is (a) specific for diabetes
      patients, (b) able to handle several different diabetes related complications,
      (c) performing as well as the widely known UKPDS Risk Engine on an external
      validation cohort.

PMID- 25953403
TI  - Ad36: skip serology, NAT we need.

PMID- 25953404
TI  - Mitigating diabetes associated ischemic stroke risk: High-risk patient
      identification.

PMID- 25953405
TI  - Microchip capillary electrophoresis with laser-induced fluorescence combined with
      one-step duplex reverse-transcription polymerase chain reaction for the rapid
      detection of Enterovirus 71 and Coxsackievirus A16 in throat swab specimens.
AB  - Enterovirus 71 and Coxsackievirus A16 are the main pathogens causing hand-foot
      mouth disease. In this paper, microchip capillary electrophoresis with laser
      induced fluorescence combined with one-step duplex reverse transcript-polymerase
      chain reaction has been developed for the detection of Enterovirus 71 and
      Coxsackievirus A16 in throat swab specimens. The specific reverse transcription
      polymerase chain reaction amplicons labeled with SYBR Orange were separated by
      microchip capillary electrophoresis and detected by laser induced fluorescence
      detector within 7 min. The intraday and interday relative standard deviation of
      migration time for DNA Marker was in the range of 1.36-2.94 and 2.78-3.96%,
      respectively. The detection limits were as low as 2.06 * 10(3) copies/mL for
      Enterovirus 71 and 5 * 10(3) copies/mL for Coxsackievirus A16. No cross
      reactivity was observed with rotavirus, astrovirus, norovirus, and adenovirus,
      which showed good specificity of the method. This assay was validated using 100
      throat swab specimens that were detected by real-time reverse-transcript
      polymerase chain reaction in parallel and the two methods produced the same
      results. This study provided a rapid, sensitive and specific method for the
      detection of Enterovirus 71 and Coxsackievirus A16, which make a contribution to
      significant time and cost saving for the identification and treatment of
      patients. 

PMID- 25953407
TI  - Insight into the formation mechanism of graphene quantum dots and the size effect
      on their electrochemical behaviors.
AB  - To study the formation mechanism and influencing factors of graphene quantum dots
      (GQDs), GQDs with different average sizes were prepared using a modified
      hydrothermal method with hydrogen peroxide (H2O2) as an etching agent and ammonia
      as an assistant. It is found that size-controlled GQDs were prepared by adjusting
      the amount of ammonia and porous reduced graphene oxide (PRGO) debris can be
      synthesized by reducing the hydrothermal reaction time. Structural changes of
      final products were mainly attributed to the changes in the etching ability of
      the hydroxyl radical (OH) against the reduction ability of the hydroxyl group
      (OH(-)) in different alkaline environments regulated by ammonia. Furthermore, we
      studied the electrochemical properties of GQDs and PRGO. The results showed that
      the specific capacitance of all samples increases linearly with the size and the
      smallest GQDs can work at the highest scan rate of as high as 5000 V s(-1) with
      an ultra-fast power response (tau0 = 63.3 MUs). Thus, these findings elucidate
      the formation mechanism of GQDs and demonstrate that GQDs are applicable in
      microelectronic devices with high power response requirements. 

PMID- 25953406
TI  - Genetic analysis, structural modeling, and direct coupling analysis suggest a
      mechanism for phosphate signaling in Escherichia coli.
AB  - BACKGROUND: Proper phosphate signaling is essential for robust growth of
      Escherichia coli and many other bacteria. The phosphate signal is mediated by a
      classic two component signal system composed of PhoR and PhoB. The PhoR histidine
      kinase is responsible for phosphorylating/dephosphorylating the response
      regulator, PhoB, which controls the expression of genes that aid growth in low
      phosphate conditions. The mechanism by which PhoR receives a signal of
      environmental phosphate levels has remained elusive. A transporter complex
      composed of the PstS, PstC, PstA, and PstB proteins as well as a negative
      regulator, PhoU, have been implicated in signaling environmental phosphate to
      PhoR. RESULTS: This work confirms that PhoU and the PstSCAB complex are necessary
      for proper signaling of high environmental phosphate. Also, we identify residues
      important in PhoU/PhoR interaction with genetic analysis. Using protein modeling
      and docking methods, we show an interaction model that points to a potential
      mechanism for PhoU mediated signaling to PhoR to modify its activity. This model
      is tested with direct coupling analysis. CONCLUSIONS: These bioinformatics tools,
      in combination with genetic and biochemical analysis, help to identify and test a
      model for phosphate signaling and may be applicable to several other systems.

PMID- 25953408
TI  - Contribution of nonignorable environmental factor to impairing liver disease
      mortality reduction target in China.

PMID- 25953410
TI  - Drug loading of polymer implants by supercritical CO2 assisted impregnation: A
      review.
AB  - Drug loaded implants also called drug-eluting implants have proven their benefits
      over simple implants. Among the developed manufacturing processes, the
      supercritical CO2 (scCO2) assisted impregnation has attracted growing attention
      to load Active Pharmaceutical Ingredients into polymer implants since it enables
      to recover a final implant free of any solvent residue and to operate under mild
      temperature which is suitable for processing with thermosensitive drugs. This
      paper is a review of the state-of-the-art and the application of the scCO2
      assisted impregnation process to prepare drug-eluting implants. It introduces the
      process and presents its advantages for biomedical applications. The influences
      of the characteristics of the implied binary systems and of the experimental
      conditions on the drug loading are described. Then, the various current
      applications of this process for manufacturing drug-eluting implants are
      reviewed. Finally, the new emerging variations of this process are described. 

PMID- 25953409
TI  - Treatment of genital lesions with diode laser vaporization.
AB  - BACKGROUND: Genital warts caused by human papillomavirus (HPV) infection are the
      most common sexually transmitted disease leading to anogential lesions. Although
      the laser therapy has been shown to be effective in a number of conditions, the
      use of laser diode vaporization in urological applications and the understanding
      on its effectiveness as a treatment for various urological conditions is limited.
      Therefore, the aim of this study was to evaluate the efficacy of diode laser
      vaporization as a treatment for genital lesions. METHODS: Patients presenting
      with genital lesions at the urology outpatient clinic at Coronel Mota Hospital,
      between March 2008 and October 2014, were enrolled into the study. Data collected
      included age, gender, duration of the lesion, site of the lesion and numbers of
      the lesions, length of follow-up, recurrence of lesions after treatment and
      whether there were any complications. RESULTS: A total of 92 patients were
      enrolled in the study; 92.4% (n = 85) male; mean age (+/- SD) 27.92 +/- 8.272
      years. The patients presented with a total of 296 lesions, with a median of 3
      lesions each, including penis (n = 78), urethra (n = 4) lesions, and scrotum (n =
      2) lesions. Lesions ranged in size from 0.1 to 0.5 cm(2), most commonly 0.3 cm(2)
      (n = 38; 41.3%), 0.4 cm(2) (n = 21; 22.8%) or 0.5 cm(2) (n = 20; 21.7%). Patients
      most commonly reported that they had their lesions for a duration of 12 (n = 29;
      31.5%) or 6 months (n = 23; 25.0%). Eighteen patients (19.6%) had a recurrence
      after their 1(st)/conventional treatment. There were no incidences of post
      operative infection or complications from the laser diode vaporization.
      CONCLUSIONS: Laser diode vaporization can be considered as an alternative method
      for treating genital lesions in urology, with satisfactory results in terms of
      pain, aesthetic and minimal recurrence.

PMID- 25953411
TI  - Subject-Specific Multiscale Modeling to Investigate Effects of Transcranial
      Magnetic Stimulation.
AB  - OBJECTIVE: Transcranial magnetic stimulation (TMS) is an effective intervention
      in noninvasive neuromodulation used to treat a number of neurophysiological
      disorders. Predicting the spatial extent to which neural tissue is affected by
      TMS remains a challenge. The goal of this study was to develop a computational
      model to predict specific locations of neural tissue that are activated during
      TMS. Using this approach, we assessed the effects of changing TMS coil
      orientation and waveform. MATERIALS AND METHODS: We integrated novel techniques
      to develop a subject-specific computational model, which contains three main
      components: 1) a figure-8 coil (Magstim, Magstim Company Limited,
      Carmarthenshire, UK); 2) an electromagnetic, time-dependent, nonhomogeneous,
      finite element model of the whole head; and 3) an adaptation of a previously
      published pyramidal cell neuron model. We then used our modeling approach to
      quantify the spatial extent of affected neural tissue for changes in TMS coil
      rotation and waveform. RESULTS: We found that our model shows more detailed
      predictions than previously published models, which underestimate the spatial
      extent of neural activation. Our results suggest that fortuitous sites of neural
      activation occur for all tested coil orientations. Additionally, our model
      predictions show that excitability of individual neural elements changes with a
      coil rotation of +/-15 degrees . CONCLUSIONS: Our results indicate that the
      extent of neuromodulation is more widespread than previous published models
      suggest. Additionally, both specific locations in cortex and the extent of
      stimulation in cortex depend on coil orientation to within +/-15 degrees  at a
      minimum. Lastly, through computational means, we are able to provide insight into
      the effects of TMS at a cellular level, which is currently unachievable by
      imaging modalities.

PMID- 25953412
TI  - Feasibility of using a multilingual web survey in studying the health of ethnic
      minority youth.
AB  - BACKGROUND: Monolingual Web survey is a common tool for studying adolescent
      health. However, national languages may cause difficulties for some immigrant
      origin youths, which lower their participation rate. In national surveys, the
      number of ethnic minority groups is often too small to assess their well-being.
      OBJECTIVE: We studied the feasibility of a multilingual Web survey targeted at
      immigrant-origin youths by selection of response language, and compared
      participation in different language groups with a monolingual survey. METHODS:
      The Adolescent Health and Lifestyle Survey (AHLS), Finland, with national
      languages (Finnish/Swedish) was modified into a multilingual Web survey targeted
      at a representative sample of 14- and 16-year olds (N=639) whose registry-based
      mother tongue was other than the national languages. The survey was conducted in
      2010 (16-year olds) and 2011 (14-year olds). The response rate of the
      multilingual survey in 2011 is compared with the AHLS of 2011. We also describe
      the translation process and the e-form modification. RESULTS: Of the respondents,
      57.6% answered in Finnish, whereas the remaining 42.4% used their mother tongue
      (P=.002). A majority of youth speaking Somali, Middle Eastern, Albanian, and
      Southeast Asian languages chose Finnish. The overall response rate was 48.7% with
      some nonsignificant variation between the language groups. The response rate in
      the multilingual Web survey was higher (51.6%, 163/316) than the survey with
      national languages (46.5%, 40/86) in the same age group; however, the difference
      was not significant (P=.47). The adolescents who had lived in Finland for 5 years
      or less (58.0%, 102/176) had a higher response rate than those having lived in
      Finland for more than 5 years (45.1%, 209/463; P=.005). Respondents and
      nonrespondents did not differ according to place of birth (Finland/other) or
      residential area (capital city area/other). The difference in the response rates
      of girls and boys was nearly significant (P=.06). Girls of the Somali and Middle
      Eastern language groups were underrepresented among the respondents. CONCLUSIONS:
      A multilingual Web survey is a feasible method for gathering data from ethnic
      youth, although it does not necessarily yield a higher response rate than a
      monolingual survey. The respondents answered more often in the official language
      of the host country than their mother tongue. The varying response rates by time
      of residence, ethnicity, and gender pose challenges for developing tempting
      surveys for youth.

PMID- 25953413
TI  - Cervical fractures with associated spinal cord injury in children and
      adolescents: epidemiology, costs, and in-hospital mortality rates in 4418
      patients.
AB  - BACKGROUND: Cervical spine fractures with spinal cord injury (CFSCI) can be
      devastating. We describe the epidemiology of children and adolescents with CFSCI.
      METHODS: Using the Nationwide Inpatient Sample (NIS) database, we identified 4418
      patients (<=18 years old) who had CFSCI from 2000 through 2010. Outcomes of
      interest were patient characteristics (age, sex), injury characteristics
      [fracture location, spinal cord injury (SCI) pattern], economic variables
      (duration of hospital stay, total hospital charges), and mortality. RESULTS:
      Upper cervical fractures (UCFs) occurred half as often (31.4 %) as lower cervical
      fractures (LCFs; 68.8 %). Among patients <8 years old, 73.6 % had UCFs; among
      patients >=8 years old, 72.3 % had LCFs. Overall, 68.7 % had incomplete SCI, 22.4
      % had complete SCI, 6.6 % had central cord syndrome, and 2.3 % had anterior cord
      syndrome. Patients with complete SCI had the longest hospital stays and highest
      hospital charges. The overall in-hospital mortality rate was 7.3 %, with a
      sixfold higher rate in patients <8 (30.6 %) vs. those >=8 (5.1 %) years old (p <
      0.001). There was a threefold higher mortality rate in patients with upper (13.5
      %) vs. lower (4.3 %) cervical fractures (p < 0.001). Patients with complete SCI
      had a 1.85-fold higher mortality rate than patients with other cord syndromes (p
      < 0.001). CONCLUSIONS: Patients <8 years old were more likely than older patients
      to sustain UCFs. Patients with UCFs had a significantly higher mortality rate
      than those with LCFs. Patients with complete SCI had the longest duration of
      hospital stay and highest hospital charges and in-hospital mortality rate.

PMID- 25953414
TI  - Anti-dermatophyte efficacy and environmental safety of some essential oils
      commercial and in vitro extracted pure and combined against four keratinophilic
      pathogenic fungi.
AB  - AIM: Establish new biocontrol practices with low persistence in the environment
      against dermatophyte causing mycosis. METHODS: Antimycotic activity of twenty-six
      plant-derived commercial essential oils (EOs) was evaluated against four
      dermatophyte keratinophilic fungi (Microsporum canis, Epidermophyton floccosum,
      Trichophyton rubrum and Trichophyton mentagrophytes). Commercial EOs which showed
      the strongest mycelial growth inhibitions were selected and re-extracted in vitro
      from fresh plant samples. Minimal inhibition concentration (MIC) and antifungal
      index (AI) of pure and combined extracted oils and were evaluated. All samples
      were collected and examined during the year of 2014. RESULTS: The results
      revealed that commercial EOs of Prunus armeniaca, Prunus dulcis var. amara, Olea
      europaea and Mentha piperita were the most potent antidermatophyte. The mixture
      of the extracted four oils was the strongest fungicides followed by the
      alternative two-oil combined extractions then pure extracted oils. MIC was at 50,
      25 and 12.5 MUg/disc for pure oils, two-oil combinations and four-oil mixture,
      respectively. Achieved values of AI were found variable. CONCLUSION: Using of
      natural products like plant-derived EOs instead of chemotherapy on pathogens can
      be regarded as an environmental safety mode of diseases control.

PMID- 25953415
TI  - Use of Traditional Indigenous Medicine and Complementary Medicine Among
      Indigenous Cancer Patients in Queensland, Australia.
AB  - BACKGROUND: The cancer toll on Indigenous Australians is alarming with overall
      cancer incidence and mortality rates higher and the 5-year survival rate lower
      for Indigenous Australians compared with non-Indigenous Australians. Meanwhile, a
      range of approaches to health and illness-including both complementary and
      alternative medicine (CAM) and traditional Indigenous medicine (TM)-are used by
      cancer patients. Little work has focused on Indigenous cancer patients with
      regard to CAM/TM use. This article reports findings from the first examination of
      the prevalence and profile of TM/CAM use and users among Indigenous Australians
      with cancer. METHODS: A structured questionnaire was administered via face-to
      face interviews to 248 Indigenous Australian cancer patients diagnosed with a
      range of cancer types. All received treatment and were recruited from 1 of 4
      large hospitals located in Queensland, Australia. RESULTS: A substantial
      percentage (18.7%) of Indigenous cancer patients use at least one TM/CAM for
      support with their care, including traditional Indigenous therapy use (2.8%),
      visiting a traditional Indigenous practitioner (2.8%), CAM use (10.7%), visiting
      a CAM practitioner (2.4%), and attending relaxation/meditation classes (4.0%).
      Having a higher level of educational attainment was positively associated with
      CAM practitioner consultations (P = .015). Women with breast cancer were more
      likely to attend relaxation/meditation classes (P = .019). Men with genital organ
      cancer were more likely to use traditional Indigenous therapies (P = .017) and/or
      CAM (P = .002). CONCLUSION: A substantial percentage of Indigenous Australians
      reported using TM/CAM for their cancer care, and there is a need to expand
      examination of this area of health care using large-scale studies focusing on in
      depth specific cancer(s).

PMID- 25953416
TI  - In vitro performance of prefilled CO2 absorbers with the Aisys(r).
AB  - Low flow anesthesia increases the use of CO2 absorbents, but independent data
      that compare canister life of the newest CO2 absorbents are scarce. Seven
      different pre-packed CO2 canisters were tested in vitro: Amsorb Plus, Spherasorb,
      LoFloSorb, Medisorb, Medisorb EF, LithoLyme, and SpiraLith. CO2 (160 mL min(-1))
      flowed into the tip of a 2 L breathing bag that was ventilated with a tidal
      volume of 500 mL, a respiratory rate of 10/min, and an I:E ratio of 1:1 using the
      controlled mechanical ventilation mode of the Aisys ((r)) (GE, Madison, WI, USA).
      In part I, canister life of each brand (all of the same lot) was tested with 12
      different fresh gas flows (FGF) ranging from 0.25 to 4 L min(-1). In part II,
      canister life of six canisters each of two different lots of each brand were
      tested with a 350 mL min(-1) FGF. Canister life is presented as "FCU", fractional
      canister usage, the fraction of a canister used per hour, and is defined for the
      inspired CO2 concentration (FICO2) that denotes exhaustion. In part III, canister
      life per 100 g fresh granule content was calculated. FCU decreased linearly with
      increasing FGF. The relative position of the FCU-FGF curves of the different
      brands depends on the FICO2 threshold because the exhaustion rate (the rate of
      rise once FICO2 starts to increase) differs among the brands. Intra-lot
      variability was 18 % or less. The different prepacks can be ranked according
      their efficiency (least to most efficient) as follows: Amsorb Plus = Medisorb EF
      < LoFloSorb < Medisorb = Spherasorb = LithoLyme < SpiraLith (all for an FICO2
      threshold = 0.5 %). Canister life per 100 g fresh granule content is almost twice
      as long when LiOH is used as the primary absorbent. The most important factors
      that determine canister life of prepacks in a circle breathing system are the
      chemical composition of the canister, the absolute amount of absorbent present in
      the canister, and the FICO2 replacement threshold. The use of the fractional
      canister usage allows cost comparisons among different prepacks. Results should
      not be extrapolated to prepacks that fit onto other anesthesia machines.

PMID- 25953417
TI  - Microarray Analysis of Immunity Against WSSV in Response to Injection of Non
      specific Long dsRNA in Kuruma Shrimp, Marsupenaeus japonicus.
AB  - Injection of shrimp with non-specific double-stranded RNA (dsRNA) of diverse
      lengths, sequences, and base compositions is known to induce non-specific
      immunity and protect against lethal disease, although the mechanisms are unclear.
      Previous shrimp studies examined the effects of non-specific RNA on particular
      pathways, while their global effects have not been examined. To understand the
      global effects of non-specific RNA in shrimp, we injected kuruma shrimp
      (Marsupenaeus japonicus) with a dsRNA and a small interfering RNA (siRNA) that is
      not specific to any gene in the shrimp genome and then examined global gene
      expression at 24 and 48 h with a microarray. For the non-specific RNA, we chose
      double-stranded green fluorescent protein (dsGFP) and siGFP because they are
      commonly used as mock controls and their effects on shrimp have not yet been
      studied. Injection of PBS was used as a control. The microarray results showed
      that many genes were up-regulated and some were down-regulated by dsGFP. In
      addition, dsGFP injection increased survival following WSSV challenge. The
      changes in expression for several genes were confirmed by quantitative PCR. The
      up-regulated genes included genes for eight immune-related proteins: c-type
      lectin 2, hemocyte homeostasis-associated protein, viral responsive protein,
      fibrinogen-related protein 1, sid-1 like protein, argonaute 2, Dicer 2, and heat
      shock protein 90. These results show that injection of shrimp with non-specific
      dsRNA hinders viral accumulation and prevents significant mortalities.

PMID- 25953418
TI  - Current practices used for the prevention of central venous catheter-associated
      infection in hematopoietic stem cell transplantation recipients: a survey from
      the Infectious Diseases Working Party and Nurses' Group of EBMT.
AB  - BACKGROUND: Central line-associated bloodstream infection (CLABSI) is one of the
      most common infectious complications after hematopoietic stem cell
      transplantation. To prevent this complication, international guidelines recommend
      the implementation of the CLABSI 'prevention bundle' consisting of hand hygiene,
      full barrier precautions, cleaning the insertion site with chlorhexidine,
      avoiding femoral sites for insertion, and removing unnecessary catheters. The aim
      of this survey was to analyze to what extent European Group for Blood and Marrow
      Transplantation (EBMT) centers have included the CLABSI prevention bundle in
      practice. METHODS: A questionnaire used for data collection was sent to the 545
      EBMT centers worldwide, 103 of which responded. RESULTS: All 5 components of the
      CLABSI prevention bundle were recorded in 28% of the centers' standard operating
      procedures (SOP), and 21% of the centers answered that they used all of the
      bundle components in clinical practice. The most common recommendation absent
      from the SOP was specification of all the components of full barrier precautions
      (43% of the centers did not include at least 1 component). Skin disinfection with
      chlorhexidine before catheter insertion was reported by 66% centers. CLABSI rates
      were monitored in 21% of centers. CONCLUSIONS: Although most of the centers
      lacked 1 or more of the CLABSI prevention bundle components in their SOP,
      improvements could easily be made by updating the centers' SOP. The first
      important step is introduction of CLABSI rate monitoring in this high-risk
      patient population.

PMID- 25953420
TI  - Correction: Paclitaxel-Loaded PEG-PE-Based Micellar Nanopreparations Targeted
      with Tumor-Specific Landscape Phage Fusion Protein Enhance Apoptosis and
      Efficiently Reduce Tumors.

PMID- 25953419
TI  - Structure-Activity Relationships, Pharmacokinetics, and in Vivo Activity of
      CYP11B2 and CYP11B1 Inhibitors.
AB  - CYP11B2, the aldosterone synthase, and CYP11B1, the cortisol synthase, are two
      highly homologous enzymes implicated in a range of cardiovascular and metabolic
      diseases. We have previously reported the discovery of LCI699, a dual CYP11B2 and
      CYP11B1 inhibitor that has provided clinical validation for the lowering of
      plasma aldosterone as a viable approach to modulate blood pressure in humans, as
      well normalization of urinary cortisol in Cushing's disease patients. We now
      report novel series of aldosterone synthase inhibitors with single-digit
      nanomolar cellular potency and excellent physicochemical properties. Structure
      activity relationships and optimization of their oral bioavailability are
      presented. An illustration of the impact of the age of preclinical models on
      pharmacokinetic properties is also highlighted. Similar biochemical potency was
      generally observed against CYP11B2 and CYP11B1, although emerging structure
      selectivity relationships were noted leading to more CYP11B1-selective analogs. 

PMID- 25953421
TI  - Fatigue during and after cardiac rehabilitation.
AB  - OBJECTIVE: To estimate fatigue during and after a multidisciplinary cardiac
      rehabilitation programme and its association with aerobic capacity. DESIGN:
      Longitudinal cohort study. PATIENTS: A total of 121 patients with coronary artery
      disease (79% men), mean age 57 years. METHODS: Fatigue was measured with the
      Fatigue Severity Scale (FSS) and aerobic capacity with the 6-min walk test
      (6MWT). FSS scores >= 4 were defined as fatigue and >5.1 as severe fatigue.
      Measurements were taken before (T0) and after rehabilitation (T1) and at 1-year
      follow-up (T2). RESULTS: Fatigue decreased from 3.49 at baseline to 3.03 post
      rehabilitation (p=0.002) and decreased further to 2.75 at follow-up (p<0.001 vs
      T0). At baseline, 17.7% of patients were classified as severely fatigued. After
      cardiac rehabilitation, the prevalence decreased to 10.6% (p<0.001) and to 8.1%
      at follow-up (p=0.011 vs T0). Although the prevalence of severely fatigued
      patients decreased, it was still high compared with healthy individuals (3.5%).
      Aerobic capacity was weakly associated with a reduction in fatigue (p=0.030).
      CONCLUSION: Fatigue decreased during and after cardiac rehabilitation. However,
      the prevalence of severely fatigued patients remained high after cardiac
      rehabilitation. Fatigue should be identified at an early stage in order to
      provide additional programmes aiming to reduce severe fatigue.

PMID- 25953422
TI  - Male Escorts' and Male Clients' Sexual Behavior During Their Last Commercial
      Sexual Encounter: Comparing and Contrasting Findings from Two Online Studies.
AB  - Much of what is known about commercial sexual encounters between men is based on
      data gathered from escorts. With few exceptions, studies have not compared male
      clients' reports of behavior during commercial sexual encounters with male
      escorts'. The present study draws from two datasets, a 2012 survey of clients (n
      = 495) and a 2013 survey of escorts (n = 387)--both used virtually identical
      measures of sexual behavior during the most recent commercial sexual encounter.
      For clients and escorts, the majority eschewed having sex without a condom, and
      kissing and oral sex were among the most common behaviors reported. Using
      logistic regression, both samples were compared across 15 sexual behaviors,
      finding significant differences in six--the escort sample had greater odds of
      reporting their last commercial sexual encounter involved watching the client
      masturbate, viewing porn, role play (dad/son, dominant/submissive), and having
      prior sexual experience with their commercial partner. The escort sample had
      lower odds of reporting that the client watched the escort masturbate, and being
      told partner's HIV status. In multivariable modeling, both samples did not
      significantly differ in reports of condomless anal sex. Male-male commercial
      sexual encounters appear to be involved in a wide range of sexual behaviors, many
      of which convey low-to-no risk of HIV transmission.

PMID- 25953423
TI  - Flexible modelling of simultaneously interval censored and truncated time-to
      event data.
AB  - This paper deals with the analysis of data from a HET-CAM(VT) experiment. From a
      statistical perspective, such data yield many challenges. First of all, the data
      are typically time-to-event like data, which are at the same time interval
      censored and right truncated. In addition, one has to cope with overdispersion as
      well as clustering. Traditional analysis approaches ignore overdispersion and
      clustering and summarize the data into a continuous score that can be analysed
      using simple linear models. In this paper, a novel combined frailty model is
      developed that simultaneously captures all of the aforementioned statistical
      challenges posed by the data.

PMID- 25953424
TI  - The prognostic value of EGFR overexpression and amplification in Esophageal
      squamous cell Carcinoma.
AB  - BACKGROUND: In view of the prominent role in cancer cell biology and alteration
      in substantial numbers of ESCC, defining EGFR molecular characteristics relevant
      to patient prognosis is of great importance. Therefore, we analyzed the protein
      expression and gene copy variation of the epithelial growth factor receptor
      (EGFR) in Chinese esophageal squamous cell carcinoma (ESCC) and explored the
      possible associations with various features of the tumors and survival of the
      patients. METHODS: Sections were made from tissue microarray composed of 96 ESCC,
      and examined for EGFR expression by means of immunohistochemistry (IHC) and for
      EGFR gene amplification by means of fluorescence in situ hybridization (FISH).
      The results of IHC were evaluated with six different reported scoring systems.
      Correlation with clinical features and survival was evaluated using chi-square
      test and Kaplan-Meier analysis. RESULTS: EGFR overexpression according to scoring
      system 1 significantly correlated with advanced lymph node involvement (P =
      0.046), patient disease specific free survival (DFS) (P = 0.006) and overall
      survival (OS) (P = 0.007). No such association was observed using other 5 scoring
      systems (P > 0.05 ). EGFR amplification was associated with lymph node metastasis
      (P = 0.028), but not correlated with DFS and OS until 20 months. CONCLUSIONS:
      EGFR IHC overexpression evaluated by scoring system 1 might be suitable to be
      used in predicting patients survival in ESCC. EGFR gene amplification showed
      delayed prognostic information after 20 months.

PMID- 25953425
TI  - High-Pressure Transvenous Perfusion of the Upper Extremity in Human Muscular
      Dystrophy: A Safety Study with 0.9% Saline.
AB  - We evaluated safety and feasibility of high-pressure transvenous limb perfusion
      in an upper extremity of adult patients with muscular dystrophy, after completing
      a similar study in a lower extremity. A dose escalation study of single-limb
      perfusion with 0.9% saline was carried out in nine adults with muscular
      dystrophies under intravenous analgesia. Our study demonstrates that it is
      feasible and definitely safe to perform high-pressure transvenous perfusion with
      0.9% saline up to 35% of limb volume in the upper extremities of young adults
      with muscular dystrophy. Perfusion at 40% limb volume is associated with short
      lived physiological changes in peripheral nerves without clinical correlates in
      one subject. This study provides the basis for a phase 1/2 clinical trial using
      pressurized transvenous delivery into upper limbs of nonambulatory patients with
      Duchenne muscular dystrophy. Furthermore, our results are applicable to other
      conditions such as limb girdle muscular dystrophy as a method for delivering
      regional macromolecular therapeutics in high dose to skeletal muscles of the
      upper extremity. 

PMID- 25953426
TI  - Diabetes is associated with persistent pain after hip and knee replacement.
AB  - BACKGROUND AND PURPOSE: In some patients, for unknown reasons pain persists after
      joint replacement, especially in the knee. We determined the prevalence of
      persistent pain following primary hip or knee replacement and its association
      with disorders of glucose metabolism, metabolic syndrome (MetS), and obesity.
      PATIENTS AND METHODS: The incidence of pain in the operated joint was surveyed 1
      2 years after primary hip replacement (74 patients (4 bilateral)) or primary knee
      replacement (119 patients (19 bilateral)) in 193 osteoarthritis patients who had
      participated in a prospective study on perioperative hyperglycemia. Of the 155
      patients who completed the survey, 21 had undergone further joint replacement
      surgery during the follow-up and were excluded, leaving 134 patients for
      analysis. Persistent pain was defined as daily pain in the operated joint that
      had lasted over 3 months. Factors associated with persistent pain were evaluated
      using binary logistic regression with adjustment for age, sex, and operated
      joint. RESULTS: 49 of the 134 patients (37%) had a painful joint and 18 of them
      (14%) had persistent pain. A greater proportion of knee patients than hip
      patients had a painful joint (46% vs. 24%; p = 0.01) and persistent pain (20% vs.
      4%; p = 0.007). Previously diagnosed diabetes was strongly associated with
      persistent pain (5/19 vs. 13/115 in those without; adjusted OR = 8, 95% CI: 2-38)
      whereas MetS and obesity were not. However, severely obese patients (BMI >= 35)
      had a painful joint (but not persistent pain) more often than patients with BMI <
      30 (14/21 vs. 18/71; adjusted OR = 5, 95% CI: 2-15). INTERPRETATION: Previously
      diagnosed diabetes is a risk factor for persistent pain in the operated joint 1-2
      years after primary hip or knee replacement.

PMID- 25953427
TI  - Inkjet printing for biosensor fabrication: combining chemistry and technology for
      advanced manufacturing.
AB  - Inkjet printing is emerging at the forefront of biosensor fabrication
      technologies. Parallel advances in both ink chemistry and printers have led to a
      biosensor manufacturing approach that is simple, rapid, flexible, high
      resolution, low cost, efficient for mass production, and extends the capabilities
      of devices beyond other manufacturing technologies. Here we review for the first
      time the factors behind successful inkjet biosensor fabrication, including
      printers, inks, patterning methods, and matrix types. We discuss technical
      considerations that are important when moving beyond theoretical knowledge to
      practical implementation. We also highlight significant advances in biosensor
      functionality that have been realised through inkjet printing. Finally, we
      consider future possibilities for biosensors enabled by this novel combination of
      chemistry and technology. 

PMID- 25953428
TI  - DNA Three-Way Junctions Stabilized by Hydrophobic Interactions for Creation of
      Functional Nanostructures.
AB  - The construction of nanomaterials from oligonucleotides by modular assembly
      invariably requires the use of branched nucleic acid architectures such as three-
      and four-way junctions (3WJ and 4WJ). We describe the stabilization of DNA 3WJ by
      using non-nucleotide lipophilic spacers to create a hydrophobic pocket within the
      junction space. Stabilization of nucleic acid junctions is of particular
      importance when constructing nanostructures in the "ultra-nano" size range (<20
      nm) with shorter double-stranded regions. UV thermal melting studies show that
      lipophilic spacers strategically placed within the junction space significantly
      increased thermal stability. For a 3WJ with eight base pair arms, thermal
      stability was increased from 30.5  degrees C for the unmodified junction to a
      maximum stability of 55.0  degrees C. The stability of the junction can be
      modulated within this temperature range by using the appropriate combinations of
      spacers.

PMID- 25953429
TI  - Retention ratio and nonequilibrium bandspreading in asymmetrical flow field-flow
      fractionation.
AB  - In asymmetrical flow field-flow fractionation (As-FlFFF), only the membrane
      covered accumulation wall is permeable to fluid; the opposite channel wall is
      impermeable. Fluid enters the channel at the inlet and exits partly through the
      membrane-covered accumulation wall and partly through the channel outlet. This
      means that not only does the volumetric channel flow rate decrease along the
      channel length as fluid exits through the membrane but also the cross-channel
      component to fluid velocity must approach zero at the impermeable wall. This
      dependence of cross-channel fluid velocity on distance across the channel
      thickness influences the equilibrium concentration profile for the sample
      components introduced to the channel. The concentration profile departs from the
      exponential profile predicted for the ideal model of field-flow fractionation.
      This influences both the retention ratio and the principal contribution to
      bandspreading--the nonequilibrium contribution. The derivation of an equation for
      the nonequilibrium bandspreading parameter chi in As-FlFFF is presented, and its
      numerical solution graphed. At high retention, it is shown that the solutions for
      both retention ratio R and chi converge on those for the ideal model, as
      expected. At lower levels of retention, the departures from the ideal model are
      significant, particularly for bandspreading. For example, at a level of retention
      corresponding to a retention parameter lambda of 0.05, R is almost 4% higher than
      for the ideal model (0.28047 as compared to 0.27000) but the value of chi is
      almost 60% higher. The equations presented for both R and chi include a first
      order correction for the finite size of the particles--the steric exclusion
      correction. These corrections are shown to be significant for particle sizes
      eluting well before steric inversion. For example, particles of half the
      inversion diameter are predicted to elute 25% slower and to show almost 40%
      higher bandspreading when steric effects are not accounted for. The work
      presented contributes to the fundamental theory of As-FlFFF and allows
      quantitative prediction of both retention and bandspreading at all levels of
      retention.

PMID- 25953430
TI  - The retinoid-related orphan receptor alpha is essential for the end-stage
      effector phase of experimental epidermolysis bullosa acquisita.
AB  - Genetic studies have added to the understanding of complex diseases. Here, we
      used a combined genetic approach for risk-loci identification in a prototypic,
      organ-specific, autoimmune disease, namely experimental epidermolysis bullosa
      acquisita (EBA), in which autoantibodies to type VII collagen (COL7) and
      neutrophil activation cause mucocutaneous blisters. Anti-COL7 IgG induced
      moderate blistering in most inbred mouse strains, while some showed severe
      disease or were completely protected. Using publicly available genotyping data,
      we identified haplotype blocks that control blistering and confirmed two
      haplotype blocks in outbred mice. To identify the blistering-associated genes,
      haplotype blocks encoding genes that are differentially expressed in EBA-affected
      skin were considered. This procedure identified nine genes, including retinoid
      related orphan receptor alpha (RORalpha), known to be involved in neurological
      development and function. After anti-COL7 IgG injection, RORalpha+/- mice showed
      reduced blistering and homozygous mice were completely resistant to EBA
      induction. Furthermore, pharmacological RORalpha inhibition dose-dependently
      blocked reactive oxygen species (ROS) release from activated neutrophils but did
      not affect migration or phagocytosis. Thus, forward genomics combined with
      multiple validation steps identifies RORalpha to be essential to drive
      inflammation in experimental EBA.

PMID- 25953431
TI  - Rural Healthy People 2020: New Decade, Same Challenges.
AB  - PURPOSE: The health of rural America is more important than ever to the health of
      the United States and the world. Rural Healthy People 2020's goal is to serve as
      a counterpart to Healthy People 2020, providing evidence of rural stakeholders'
      assessment of rural health priorities and allowing national and state rural
      stakeholders to reflect on and measure progress in meeting those goals. The
      specific aim of the Rural Healthy People 2020 national survey was to identify
      rural health priorities from among the Healthy People 2020's (HP2020) national
      priorities. METHODS: Rural health stakeholders (n = 1,214) responded to a
      nationally disseminated web survey soliciting identification of the top 10 rural
      health priorities from among the HP2020 priorities. Stakeholders were also asked
      to identify objectives within each national HP2020 priority and express concerns
      or additional responses. FINDINGS AND CONCLUSIONS: Rural health priorities have
      changed little in the last decade. Access to health care continues to be the most
      frequently identified rural health priority. Within this priority, emergency
      services, primary care, and insurance generate the most concern. A total of 926
      respondents identified access as the no. 1 rural health priority, followed by,
      no. 2 nutrition and weight status (n = 661), no. 3 diabetes (n = 660), no. 4
      mental health and mental disorders (n = 651), no. 5 substance abuse (n = 551),
      no. 6 heart disease and stroke (n = 550), no. 7 physical activity and health (n =
      542), no. 8 older adults (n = 482), no. 9 maternal infant and child health (n =
      449), and no. 10 tobacco use (n = 429).

PMID- 25953432
TI  - Prenatal developmental safety of functional polyurethanes for cardiovascular
      implants.
AB  - Historically, polyurethanes have been regarded as promising materials for
      cardiovascular implants such as vascular grafts and heart valves. Their
      biocompatibility has been thoroughly investigated. However, their developmental
      toxicity is seldom reported. We recently developed two polycarbonate urethanes
      with polyethylene glycol side chains capped with epoxy or amino groups that can
      further react with specific biomolecules. Both materials in microfibrillar
      morphology were subjected to saline extraction at 70  degrees C to prompt
      material hydrolysis. Proton nuclear magnetic resonance, Fourier transform
      infrared spectroscopy, and gel permeation chromatography all confirmed the
      degradation of the polyurethanes. The saline extracts containing the degradation
      products were administered to Sprague-Dawley female rats on day 7 to 16 of
      gestation via tail vein injection at a dose of 5 mL/kg/day. No maternal toxicity
      was observed. No external, skeletal, and visceral malformations in fetuses were
      found associated with the test materials, implying their safety to both adult
      rats and the offspring. Further investigations for applications in vascular
      grafts are under way.

PMID- 25953433
TI  - Novel roles of the unfolded protein response in the control of tumor development
      and aggressiveness.
AB  - The hallmarks of cancer currently define the molecular mechanisms responsible for
      conferring specific tumor phenotypes. Recently, these characteristics were also
      connected to the status of the secretory pathway, thereby linking the
      functionality of this cellular machinery to the acquisition of cancer cell
      features. The secretory pathway ensures the biogenesis of proteins that are
      membrane-bound or secreted into the extracellular milieu and can control its own
      homeostasis through an adaptive signaling pathway named the unfolded protein
      response (UPR). In the present review, we discuss the specific features of the
      UPR in various tumor types and the impact of the selective activation of this
      pathway on cell transformation, tumor development and aggressiveness. 

PMID- 25953434
TI  - Cross-talk between Epstein-Barr virus and microenvironment in the pathogenesis of
      lymphomas.
AB  - Epstein-Bar virus (EBV) is known to directly drive the neoplastic transformation
      of lymphoid cells resulting in the development of a variety of
      lymphoproliferative disorders. Emerging evidence however indicates that this
      final outcome is also related to the ability of EBV to shape microenvironment
      making it more conducive to cell transformation. Indeed, EBV up-regulates the
      production of several soluble factors promoting the growth and/or the survival of
      lymphoid cells and orchestrates a variety of complex mechanisms favoring their
      escape from anti-tumor immune responses. Furthermore, EBV-infected B lymphocytes
      actively secrete exosomes and recent investigation is now shedding light on the
      content and functional impact that these bioactive vesicles may have in bystander
      recipient cells. The complex interplay existing between EBV-carrying lymphoid
      cells and tumor microenvironment is now offering attractive targets of therapy
      that can be exploited to improve current therapeutic strategies for EBV-driven
      lymphoid malignancies. 

PMID- 25953435
TI  - Tribotronic Logic Circuits and Basic Operations.
AB  - A tribotronic logic device is fabricated to convert external mechanical stimuli
      into logic level signals, and tribotronic logic circuits such as NOT, AND, OR,
      NAND, NOR, XOR, and XNOR gates are demonstrated for performing mechanical
      electrical coupled tribotronic logic operations, which realize the direct
      interaction between the external environment and the current silicon integrated
      circuits. 

PMID- 25953437
TI  - A hollow-fibre column system to effectively prepare washed platelets.
AB  - BACKGROUND AND OBJECTIVES: We developed a hollow-fibre column system specifically
      adapted to prepare washed platelet concentrates (WPCs). This study was performed
      to evaluate the efficacy of the hollow-fibre column system for preparing WPCs.
      MATERIALS AND METHODS: First, the percentages of platelet (PLT) recovery and
      remaining plasma proteins were calculated by determining the PLT count, volume
      and plasma protein levels in both the prewash and postwash. Secondly, washed PLTs
      and unwashed control PLTs were stored for 5 days, and the changes during this 5
      day storage of in vitro PLT characteristics were determined. RESULTS: The hollow
      fibre column system effectively removed >98% of plasma in platelet concentrates
      (PCs), and the PLT recovery was 97% on an average. The CD62P-expression level on
      washed PLTs immediately after washing was approximately twofold higher than that
      on prewashed PLTs as well as on PLTs washed via manual methods or cell washing
      devices. Until day 5 during storage, PLT aggregability, hypotonic shock response
      and swirling scores of washed PLTs were not significantly different from those of
      the control PCs. CONCLUSION: Our novel hollow-fibre column system proved valuable
      in preparing washed PLTs with <2% of residual plasma proteins and high recovery
      of PLTs.

PMID- 25953436
TI  - Prognostic model for mantle cell lymphoma in the rituximab era: a nationwide
      study in Japan.
AB  - Mantle cell lymphoma (MCL) is essentially incurable with conventional
      chemotherapy. The MCL International Prognostic Index (MIPI) is a validated
      specific prognostic index, but was derived from patients with advanced-stage
      disease primarily in the pre-rituximab era. We analysed 501 MCL patients (median
      age, 67 years; range 22-90) treated with rituximab-containing chemotherapy, and
      evaluated the prognostic factors adjusted by the treatment. Five-year overall
      survival (OS) in the low, intermediate and high MIPI groups was 74%, 70% and 35%,
      respectively. Additional to MIPI risk factors, multivariate analysis revealed
      that low serum albumin and bone-marrow involvement were also significantly
      associated with a poor outcome. The revised-MIPI (R-MIPI) was constructed using
      six factors, namely age, performance status, white blood cell count, serum
      lactate dehydrogenase, bone-marrow involvement and serum albumin, which is
      divided into four prognostic groups. Five-year OS in low, low-intermediate (L-I),
      high-intermediate (H-I) and high R-MIPI groups was 92%, 75%, 61% and 19%,
      respectively. Hazard ratio for OS of L-I, H-I and high risk to low risk patients
      were 5.4, 8.3 and 33.0, respectively. R-MIPI, a new prognostic index with easy
      application to the general patient population, shows promise for identifying low-
      and high-risk MCL patients in the rituximab era. 

PMID- 25953438
TI  - Congenital Thoracic Venous Anomalies in Adults: Morphologic MR Imaging.
AB  - Congenital anomalies of the thoracic veins are rare yet important developmental
      abnormalities, usually classified into systemic and pulmonary. They may be
      encountered incidentally; as such the radiologist must be aware of their imaging
      presentation and clinical relevance. Furthermore, to understand these anomalies,
      knowledge of the embryological development and of the normal anatomy of the
      thoracic veins is required. In the age of non-invasive imaging modalities,
      magnetic resonance is paramount for the characterization of these developmental
      abnormalities. 

PMID- 25953439
TI  - Efficacy of capecitabine monotherapy as the first-line  treatment of metastatic
      HER2-negative breast cancer.
AB  - AIMS AND BACKGROUND: Capecitabine is a potent and safe agent that can be used
      after anthracycline and taxane treatment in patients with metastatic breast
      cancer (MBC). The purpose of this study was to investigate the efficacy and
      safety of capecitabine monotherapy as a first-line treatment in human epidermal
      receptor 2 (HER2)-negative patients with MBC. METHODS AND STUDY DESIGN: In this
      single-center trial, a total of 109 HER2-negative patients with MBC who received
      capecitabine monotherapy as first-line treatment between 2003 and 2014 were
      retrospectively analyzed. Kaplan-Meier survival analysis was carried out for
      progression-free survival (PFS) and for overall survival (OS). Two-sided p values
      of <0.05 were considered statistically significant. RESULTS: Median PFS was 7.0
      +/- 0.67 (confidence interval (CI) 5.6-8.3) months and median OS was 30 +/- 4.1
      (CI 21.8- 38.1) months. First-line capecitabine treatment for HER2-negative MBC
      was more effective in the estrogen receptor (ER)-positive patient population
      compared to the ER-negative group (median PFS 9 vs 4 months (p = 0.002), median
      OS 33 vs 21 months (p = 0.01)). Indeed, the overall response rate in the ER
      negative group was 16%, while this was calculated as 38% for ER-positive cases.
      While most of our patient population was treated with a higher dose (1250 mg/m2),
      the observed grade 3-4 toxicities were lower compared to some previously reported
      phase II and phase III capecitabine studies. CONCLUSIONS: Capecitabine
      monotherapy is an effective and safe regimen for ER-positive, HER2-negative
      patients with MBC. Its low toxicity profile compared to other intravenous
      cytotoxic agents and the ease of its oral administration make this agent a
      preferable option for both physicians and patients.

PMID- 25953440
TI  - Primary TKI resistance in advanced non-small cell lung cancer with EGFR mutation:
      an open question.
AB  - The malignant behavior of non-small cell lung cancer (NSCLC) is caused by
      different driver mutations, which may include alterations in the epidermal growth
      factor receptor (EGFR) signaling pathway. Activating mutations in exons 19 or 21
      of EGFR in NSCLC are associated with increased sensitivity to EGFR tyrosine
      kinase inhibitors (TKIs) such as gefitinib and erlotinib. However, approximately
      10% of NSCLC patients show primary resistance to TKIs, and the resistance
      mechanism is poorly understood. We report the case of a 72-year-old nonsmoking
      Caucasian woman who underwent pulmonary segmentectomy for right peripheral T1N0M0
      NSCLC. The tumor was an adenocarcinoma, with a point mutation in exon 21 of EGFR
      and with negative ALK gene rearrangement. Postoperative CT scan revealed right
      pleural effusion and abundant ascites without metastases to parenchymal organs.
      After paracentesis with positive cytology for adenocarcinoma, the patient started
      therapy with oral gefitinib 250 mg/day. CT scan after 2 months revealed disease
      progression with an increase in the pleural effusion (right and left) and
      ascites, as well as the appearance of solid tissue involving the right main
      bronchus and bronchus intermedius. Gefitinib was stopped and the patient died 1
      month later of progressive NSCLC. The peculiarities of our case are the site of
      the metastatic disease and the complete lack of a response to gefitinib in a
      patient with an activating mutation in EGFR exon 21. 

PMID- 25953441
TI  - Widespread renal polycystosis induced by crizotinib.
AB  - With the widespread availability of biological antitumor drugs, the current scene
      of chemotherapies is changing. New chemotherapy agents, such as crizotinib, an
      inhibitor of anaplastic lymphoma kinase (ALK) and ROS1, usually used in
      pretreated advanced ALK-positive non-small-cell lung carcinoma, are more often
      used, and a description of the onset of side effects with suggestions for their
      management could be of interest for physicians. We describe a case of diffuse and
      aggressive renal polycystosis induced by crizotinib, which regressed after
      therapy, which could be of interest considering its wide extension and
      disappearance after the end of treatment. We also suggest some considerations
      from the literature and from the case reported that could be helpful in the
      management of this condition, which is known to be caused by crizotinib
      treatment. 

PMID- 25953442
TI  - Screening the molecular targets of ovarian cancer based on bioinformatics
      analysis.
AB  - AIMS AND BACKGROUND: Ovarian cancer (OC) is the most lethal gynecologic
      malignancy. This study aims to explore the molecular mechanisms of OC and
      identify potential molecular targets for OC treatment. METHODS AND STUDY DESIGN:
      Microarray gene expression data (GSE14407) including 12 normal ovarian surface
      epithelia samples and 12 OC epithelia samples were downloaded from Gene
      Expression Omnibus database. Differentially expressed genes (DEGs) between 2
      kinds of ovarian tissue were identified by using limma package in R language
      (|log2 fold change| gt;1 and false discovery rate [FDR] lt;0.05). Protein-protein
      interactions (PPIs) and known OC-related genes were screened from COXPRESdb and
      GenBank database, respectively. Furthermore, PPI network of top 10 upregulated
      DEGs and top 10 downregulated DEGs was constructed and visualized through
      Cytoscape software. Finally, for the genes involved in PPI network, functional
      enrichment analysis was performed by using DAVID (FDR lt;0.05). RESULTS: In
      total, 1136 DEGs were identified, including 544 downregulated and 592 upregulated
      DEGs. Then, PPI network was constructed, and DEGs CDKN2A, MUC1, OGN, ZIC1, SOX17,
      and TFAP2A interacted with known OC-related genes CDK4, EGFR/JUN, SRC, CLI1,
      CTNNB1, and TP53, respectively. Moreover, functions about oxygen transport and
      embryonic development were enriched by the genes involved in the network of
      downregulated DEGs. CONCLUSIONS: We propose that 4 DEGs (OGN, ZIC1, SOX17, and
      TFAP2A) and 2 functions (oxygen transport and embryonic development) might play a
      role in the development of OC. These 4 DEGs and known OC-related genes might
      serve as therapeutic targets for OC. Further studies are required to validate
      these predictions.

PMID- 25953443
TI  - Hope in severe disease: a review of the literature on the construct and the tools
      for assessing hope in the psycho-oncologic setting.
AB  - AIMS AND BACKGROUND: Research on the topic of hope began a long time ago but,
      more recently, interest in this construct has focused mainly on the development
      of psychometric tools for its assessment. The 2 steps of the present article are
      defining the construct of hope by completing a preliminary review of the
      literature and analyzing the tools used to assess hope in the setting of
      oncologic medicine, conducting a systematic review of the existing scientific
      literature. METHODS AND STUDY DESIGN: Our study was conducted in 2 stages. The
      first stage involved a nonsystematic preliminary review of the literature, the
      second a systematic search in all the medical journals contained in the Medline
      database as of 2012. The literature identified at the first stage was divided
      according to several topical categories, i.e., theoretical, empirical, and
      clinical works on the construct of hope. In the second systematic search, we
      identified the main psychometric tools used to measure hope in the field of
      clinical oncology and assessed their validity. RESULTS: A total of 22 articles
      were identified. What emerged when we pooled the findings of our 2 lines of
      research was that, despite its broad theoretical definitions, the construct of
      hope can be broken down to a few constituent elements when hope is studied using
      currently available psychometric tools. In particular, these identified
      constituent elements were coping, spiritual well-being, quality of life,
      distress, and depression. CONCLUSIONS: The factors contained in the construct of
      hope include temporality, future, expectancy, motivation, and interconnectedness.
      The review of the scientific literature does not reveal a clear definition of
      hope. Multidisciplinary studies are needed to communicate different perspectives
      (medical, psychological, spiritual, theological) among each other for better
      definition of the constituent elements of hope in order to support the hope with
      specific interventions.

PMID- 25953444
TI  - Trends in survival for patients with metastatic breast cancer: is survival
      improving?
AB  - INTRODUCTION: The treatment of patients with metastatic breast cancer (mBC) is
      one of the most difficult problems in clinical oncology. Clinical trial results
      suggest that novel therapies may be having a favorable impact on the survival of
      mBC patients, but the real impact of new therapies on OS rates has yet to be
      established. The aim of this outcome study was to evaluate the most reliable
      parameters to define the long-term result in terms of OS of different treatment
      strategies for mBC patients in a real-world clinical practice. MATERIALS AND
      METHODS: A retrospective analysis of consecutive patients diagnosed with mBC
      between February 2001 and December 2008 and treated at our medical oncology unit
      was performed. RESULTS: We evaluated 70 female patients. At the last follow-up
      all patients had died. Median OS was 31.55 months (range, 2.33-100.13). There was
      no statistically significant difference in OS (p = 0.284) between the period 2001
      2004 and the period 2005-2008. We did not find any statistically significant
      difference in OS even in the transition from one year to the next (p = 0.154).
      CONCLUSIONS: The results of the current analysis suggest that the OS of women
      with mBC has not improved in the last years. However, these results should be
      interpreted with caution, considering the difficulty of determining changes in
      survival over time. Larger studies are needed to corroborate our findings.

PMID- 25953445
TI  - Erlotinib-associated interstitial lung disease in advanced pancreatic carcinoma:
      a case report and literature review.
AB  - The combination of erlotinib and gemcitabine is a recognized option for patients
      with metastatic pancreatic cancer whose common adverse events such as skin rash,
      diarrhea, or fatigue are usually easily manageable. Interstitial lung disease
      (ILD) is a life-threatening toxicity reported in patients with non-small-cell
      lung cancers treated with epidermal growth factor receptor-tyrosine kinase
      inhibitors or gemcitabine. This side effect is extremely rare in patients with
      pancreatic cancer. We report fatal treatment-related ILD that occurred in a 67
      year-old patient with metastatic pancreatic cancer. Risk factors and
      pathophysiology of ILD need further investigation but caution is highly
      recommended for patients with an underlying pulmonary disease when using
      erlotinib in monotherapy or combination therapy. 

PMID- 25953446
TI  - HDAC inhibitors: a new radiosensitizer for non-small-cell lung cancer.
AB  - For many decades, lung cancer has been the most common cancer and the leading
      cause of cancer death worldwide. More than 50% of non-small-cell lung cancer
      patients receive radiotherapy (alone or in combination with chemotherapy or
      surgery) during their treatment. The intrinsic radiosensitivity of tumors and
      dose-limiting toxicity restrict the curative potential of radiotherapy. Histone
      deacetylase inhibitors (HDACis) are an emerging class of agents that target
      histone deacetylase and represent promising radiosensitizers that affect various
      biological processes, such as cell growth, apoptosis, DNA repair, and terminal
      differentiation. Histone deacetylase inhibitors have been found to suppress many
      important DNA damage responses by downregulating proteins in the homologous
      recombination and nonhomologous end joining repair pathways in vitro. In this
      review, we describe the rationale for using HDACis as radiosensitizers and the
      clinical evidence regarding the use of HDACis for the treatment of non-small-cell
      lung cancer. 

PMID- 25953447
TI  - A breast cancer clinical registry in an Italian comprehensive cancer center: an
      instrument for descriptive, clinical, and experimental research.
AB  - In clinical research, many potentially useful variables are available via the
      routine activity of cancer center-based clinical registries (CCCR). We present
      the experience of the breast cancer clinical registry at Fondazione IRCCS
      "Istituto Nazionale dei Tumori" to give an example of how a CCCR can be planned,
      implemented, and used. Five criteria were taken into consideration while planning
      our CCCR: (a) available clinical and administrative databases ought to be
      exploited to the maximum extent; (b) open source software should be used; (c) a
      Web-based interface must be designed; (d) CCCR data must be compatible with
      population-based cancer registry data; (e) CCCR must be an open system, able to
      be connected with other data repositories. The amount of work needed for the
      implementation of a CCCR is inversely linked with the amount of available coded
      data: the fewer data are available in the input databases as coded variables, the
      more work will be necessary, for information technology staff, text mining
      analysis, and registrars (for collecting data from clinical records). A cancer
      registry in a comprehensive cancer center can be used for several research
      aspects, such as estimate of the number of cases needed for clinical studies,
      assessment of biobank specimens with specific characteristics, evaluation of
      clinical practice and adhesion to clinical guidelines, comparative studies
      between clinical and population sets of patients, studies on cancer prognosis,
      and studies on cancer survivorship.

PMID- 25953448
TI  - Analysis of gene profiles in glioma cells identifies potential genes, miRNAs, and
      target sites of migratory cells.
AB  - AIMS: To explore the potential molecular mechanisms involved in migratory glioma
      cells. METHODS: The gene expression profiles of GSE28167, employing human
      malignant glioma U251MG cells cultured on strictly aligned versus randomly
      oriented electrospun nanofibers of polycaprolactone, were downloaded from the
      Gene Expression Omnibus database. Gene differential expression analysis was
      carried out by the package of Gene Expression Omnibus query and limma in R
      language. The Gene Set Analysis Toolkit V2 was used for pathway analysis. Gene
      set enrichment analysis was used to screen for target sites of transcription
      factors, miRNA and small drug molecules. RESULTS: Totally 586 differentially
      expressed genes were identified and the differentially expressed genes were
      mainly enriched in the pathway of muscle cell TarBase, MAPK cascade, adipogenesis
      and epithelium TarBase. Thirty-two significant target sites of transcription
      factors, such as hsa_RTAAACA_V$FREAC2_01, were screened. The top 20 potential
      miRNAs including MIR-124A, MIR-34A and MIR-34C were screened for a constructing
      gene-miRNA interaction network. Small molecules that can inhibit the motility of
      glioma cells such as diclofenamide and valinomycin were mined. By integrating the
      regulatory relationships among transcription factors, miRNAs and differentially
      expressed genes, we found that 7 differentially expressed genes, including SOX4,
      ANKRD28 and CCND1, might play crucial roles in the migration of glioma cells.
      CONCLUSIONS: The screened migration-associated genes, significant pathways, and
      small molecules give us new insight for the mechanism of migratory glioma cells.
      Interest in such genes as potential target genes in the treatment of glioblastoma
      justifies functional validation studies.

PMID- 25953449
TI  - Bladder cancer diagnosis: the role of CT urography.
AB  - AIMS AND BACKGROUND: To evaluate the diagnostic performance of computed
      tomography urography (CTU), we first compared it with cystoscopy and subsequently
      analyzed which CTU phase of acquisition has the highest diagnostic accuracy in
      identifying bladder cancer. METHODS: In 2013, 177 patients underwent both
      cystoscopy and CTU. For all acquisition phases, we calculated sensitivity,
      specificity, diagnostic accuracy, and positive and negative predictive value (PPV
      and NPV, respectively). We also evaluated the Cohen kappa coefficient. RESULTS:
      Computed tomography urography sensitivity, specificity, diagnostic accuracy, PPV,
      and NPV were as follows: 96.3%, 86.4%, 92.8%, 92.9%, and 92.7%; concordance
      calculated with Cohen kappa was good: 0.8413. The arterial acquisition phase
      showed the highest diagnostic accuracy, identifying 93.4% of all lesions.
      CONCLUSIONS: Computed tomography urography is an accurate examination for the
      diagnosis of bladder cancer, and the arterial acquisition phase provides the best
      diagnostic information.

PMID- 25953450
TI  - Importance of distinguishing between different types of health app.

PMID- 25953451
TI  - The New Nordic Diet: phosphorus content and absorption.
AB  - PURPOSE: High phosphorus content in the diet may have adverse effect on
      cardiovascular health. We investigated whether the New Nordic Diet (NND), based
      mainly on local, organic and less processed food and large amounts of fruit,
      vegetables, wholegrain and fish, versus an Average Danish Diet (ADD) would reduce
      the phosphorus load due to less phosphorus-containing food additives, animal
      protein and more plant-based proteins. METHODS: Phosphorus and creatinine were
      measured in plasma and urine at baseline, week 12 and week 26 in 132 centrally
      obese subjects with normal renal function as part of a post hoc analysis of data
      acquired from a 26-week controlled trial. We used the fractional phosphorus
      excretion as a measurement of phosphorus absorption. RESULTS: Mean baseline
      fractional phosphorus excretion was 20.9 +/- 6.6 % in the NND group (n = 82) and
      20.8 +/- 5.5 % in the ADD group (n = 50) and was decreased by 2.8 +/- 5.1 and 3.1
      +/- 5.4 %, respectively, (p = 0.6) at week 26. At week 26, the mean change in
      plasma phosphorus was 0.04 +/- 0.12 mmol/L in the NND group and -0.03 +/- 0.13
      mmol/L in the ADD group (p = 0.001). Mean baseline phosphorus intake was 1950 +/-
      16 mg/10 MJ in the NND group and 1968 +/- 22 mg/10 MJ in the ADD group and
      decreased less in the NND compared to the ADD (67 +/- 36 mg/10 MJ and -266 +/- 45
      mg/day, respectively, p < 0.298). CONCLUSION: Contrary to expectations, the NND
      had a high phosphorus intake and did not decrease the fractional phosphorus
      excretion compared with ADD. Further modifications of the diet are needed in
      order to make this food concept beneficial regarding phosphorus absorption.

PMID- 25953453
TI  - Acoustic analysis of voice in children with cleft palate and velopharyngeal
      insufficiency.
AB  - BACKGROUND: Acoustic analysis of voice can provide instrumental data concerning
      vocal abnormalities. These findings can be used for monitoring clinical course in
      cases of voice disorders. Cleft palate severely affects the structure of the
      vocal tract. Hence, voice quality can also be also affected. OBJECTIVE: To study
      whether the main acoustic parameters of voice, including fundamental frequency,
      shimmer and jitter are significantly different in patients with a repaired cleft
      palate, as compared with normal children without speech, language and voice
      disorders. MATERIALS AND METHODS: Fourteen patients with repaired unilateral
      cleft lip and palate and persistent or residual velopharyngeal insufficiency
      (VPI) were studied. A control group was assembled with healthy volunteer subjects
      matched by age and gender. Hypernasality and nasal emission were perceptually
      assessed in patients with VPI. Size of the gap as assessed by
      videonasopharyngoscopy was classified in patients with VPI. Acoustic analysis of
      voice including Fundamental frequency (F0), shimmer and jitter were compared
      between patients with VPI and control subjects. RESULTS: F0 was significantly
      higher in male patients as compared with male controls. Shimmer was significantly
      higher in patients with VPI regardless of gender. Moreover, patients with
      moderate VPI showed a significantly higher shimmer perturbation, regardless of
      gender. CONCLUSION: Although future research regarding voice disorders in
      patients with VPI is needed, at the present time it seems reasonable to include
      strategies for voice therapy in the speech and language pathology intervention
      plan for patients with VPI.

PMID- 25953454
TI  - Respiratory failure after superior-based pharyngeal flap for velopharyngeal
      insufficiency: A rare complication.
AB  - Velopharyngeal insufficiency (VPI) is an uncommon pediatric disorder often
      associated with congenital syndromes. After speech therapy, surgery is the
      standard management. Many surgical approaches to VPI repair have been reported
      and the complications of these procedures are well documented. To date, there
      have been no published cases of respiratory failure secondary to
      pneumomediastinum, pneumopericardium, and bilateral pneumothoraces with
      associated subcutaneous emphysema after superior-based pharyngeal flap. We
      present the first case in the literature. Our proposed etiology for the
      respiratory failure is air tracking from the flap donor site to the pleural
      spaces of the thoracic cavity via the visceral or prevertebral fascia following
      positive pressure ventilation. 

PMID- 25953452
TI  - Dietary inflammatory index and risk of lung cancer and other respiratory
      conditions among heavy smokers in the COSMOS screening study.
AB  - PURPOSE: To test whether the inflammatory potential of diet, as measured using
      the dietary inflammatory index (DII), is associated with risk of lung cancer or
      other respiratory conditions and to compare results obtained with those based on
      the aMED score, an established dietary index that measures adherence to the
      traditional Mediterranean diet. METHODS: In 4336 heavy smokers enrolled in a
      prospective, non-randomized lung cancer screening program, we measured
      participants' diets at baseline using a self-administered food frequency
      questionnaire from which dietary scores were calculated. Cox proportional hazards
      and logistic regression models were used to assess association between the
      dietary indices and lung cancer diagnosed during annual screening, and other
      respiratory outcomes that were recorded at baseline, respectively. RESULTS: In
      multivariable analysis, adjusted for baseline lung cancer risk (estimated from
      age, sex, smoking history, and asbestos exposure) and total energy, both DII and
      aMED scores were associated with dyspnoea (p trend = 0.046 and 0.02,
      respectively) and radiological evidence of emphysema (p trend = 0.0002 and 0.02).
      After mutual adjustment of the two dietary scores, only the association between
      DII and radiological evidence of emphysema (Q4 vs. Q1, OR 1.30, 95 % CI 1.01
      1.67, p trend = 0.012) remained statistically significant. At univariate
      analysis, both DII and aMED were associated with lung cancer risk, but in fully
      adjusted multivariate analysis, only the association with aMED remained
      statistically significant (p trend = 0.04). CONCLUSIONS: Among heavy smokers, a
      pro-inflammatory diet, as indicated by increasing DII score, is associated with
      dyspnoea and radiological evidence of emphysema. A traditional Mediterranean
      diet, which is associated with a lower DII, may lower lung cancer risk.

PMID- 25953455
TI  - Evidence of the involvement of the polymorphisms near MSX1 gene in non-syndromic
      cleft lip with or without cleft palate.
AB  - OBJECTIVE: Non-syndromic cleft lip, with or without cleft palate (NSCL/P) is a
      common craniofacial birth defect, characterised by an incomplete separation
      between nasal and oral cavities without any other congenital anomaly in humans.
      Several genes which play a role in cell differentiation, migration, growth and
      apoptosis, have been associated with clefting. The purpose of this study was to
      investigate the association between single-nucleotide polymorphisms (SNPs) near
      MSX1 gene and NSCL/P among South Indian population. METHODS: A case-control
      analysis of five single nucleotide polymorphisms near MSX1 gene (rs11726039,
      rs868257, rs6446693, rs1907998 and rs6832405) was carried out in 173 patients
      with NSCL/P and 176 unaffected controls to determine their association with
      NSCL/P. RESULTS: All SNPs were polymorphic in the study population. Comparisons
      of allele and genotype frequencies revealed that the C variant allele and the
      TC/CC genotypes of rs11726039 was significantly higher in controls than in the
      NSCL/P group (OR: 0.63; 95% CI: 0.41-0.097; p=0.037). However, neither of these
      findings remained significant after Bonferroni correction for multiple
      comparisons. The frequencies of rs868257, rs6446693, rs1907998 and rs6832405
      minor alleles and genotypes were similar between the control and NSCL/P groups.
      No significant linkage disequilibrium (LD) was observed. Genotype-genotype
      interaction and the haplotype analysis did not reveal any significant association
      with NSCL/P. CONCLUSIONS: The study results were suggestive of a positive
      association between MSX1 rs11726039 and NSCL/P in the South Indian population.

PMID- 25953456
TI  - Tumors in the parotid are not relatively more often malignant in children than in
      adults.
AB  - INTRODUCTION: Tumors of the parotid gland in children are rare and very little
      data has been published regarding the incidence of these tumors. We present a
      nationwide survey on this topic. METHODS: Data regarding benign and malignant
      tumors in the parotid gland in children from January 1st, 1990 to December 31st,
      2005 in Denmark was collected retrospectively from nationwide registries. This
      generated 61 patients for inclusion in this study. RESULTS: 85% of the tumors
      were benign and the malignant tumors made up the last 15%. The most common of the
      malignant tumors was the acinic cell carcinoma (n=4) followed by the
      mucoepidermoid carcinoma (n=3) and adenoid cystic carcinoma (n=2). The overall
      female-to-male ratio was 1.18, with a ratio of 1.08 and 2.0 in the benign and
      malignant groups, respectively. At the end of follow-up (August 1st, 2014) two
      patients had died, one with adenoid cystic carcinoma and one with mucoepidermoid
      carcinoma. Both patients had perineural invasion and involved resection margins
      at presentation. The incidence was 0.12 and 0.53 per 100,000 children of the
      malignant and benign tumors, respectively. CONCLUSION: Pleomorphic adenomas were
      the predominant neoplasm in the parotid gland in children. The most frequent of
      the malignant tumors was the acinic cell carcinoma, which is in contrast to
      previous studies. The proportion of malignant-to-benign parotid gland tumors is
      in contrast to earlier study reports not higher in children than in adults.

PMID- 25953457
TI  - Transapical transcatheter valve-in-ring implantation for failed mitral valve
      repair in the absence of radiopaque markers.

PMID- 25953458
TI  - The behavioural treatment of muscle tension voice disorders: A systematic review.
AB  - PURPOSE: A systematic review of behavioural intervention for the treatment of
      adults with muscle tension voice disorders (MTVD). METHOD: A search of 12
      electronic databases and reference lists for studies published between the years
      1990-2014 was conducted using the PRISMA guidelines. Inclusion and exclusion
      criteria included type of publication, participant characteristics, intervention,
      outcome measures and report of outcomes. Methodological quality rating scales and
      confidence in diagnostic scale supported the literature evaluation. RESULT: Seven
      papers met the inclusion criteria. Significant improvement on at least one
      outcome measure was reported for all studies. Effect sizes were small-to-large.
      Methodological qualities of research were varied. No study explicitly reported
      treatment fidelity and cumulative intervention intensity could only be calculated
      for two out of seven studies. Outcome measures were used inconsistently and less
      than half of the measures had reported reliability values. Confidence in the
      accuracy of subject diagnosis on average was rated as low. Specific "active
      ingredients" for therapeutic change were not identified. CONCLUSION: Voice
      therapy for the treatment of MTVD is associated with positive treatment outcomes;
      however, there is an obvious need for systematic and high quality research
      designs to expand the evidence base for the behavioural treatment of MTVD.

PMID- 25953459
TI  - The impact of onlooking and including bystander behaviour on judgments and
      emotions regarding peer exclusion.
AB  - We investigated judgments and emotions in contexts of social exclusion that
      varied as a function of bystander behaviour (N = 173, 12- and 16-year-olds).
      Adolescents responded to film vignettes depicting a target excluded by a group
      with no bystanders, onlooking bystanders, or bystanders who included the target.
      Adolescents were asked to judge the behaviour and attribute emotions to the
      excluding group, the excluded target, and the bystanders. Younger adolescents
      judged the behaviour of the excluding group as more wrong than older adolescents
      when there were no bystanders present, indicating that the presence of bystanders
      was viewed as lessening the negative outcome of exclusion by the younger group.
      Yet, bystanders play a positive role only when they are includers, not when they
      are silent observers. This distinction was revealed by the findings that
      adolescents rated the behaviour of onlooking bystanders as more wrong compared
      with the behaviour of including bystanders. Moreover, all adolescents justified
      the inclusive behaviour more frequently with empathy than the onlooking
      behaviour. Adolescents also anticipated more empathy to including bystanders than
      to onlooking bystanders, as well as anticipated more guilt to onlooking
      bystanders than including bystanders. The findings are discussed in light of the
      role of group norms and group processes regarding bystanders' roles in social
      exclusion peer encounters. 

PMID- 25953460
TI  - Acquisition of a t(11;14)(q13;q32) in clonal evolution in a follicular lymphoma
      with a t(14;18)(q32;q21) and t(3;22)(q27;q11.2).
AB  - Chromosome translocations involving an immunoglobulin (IG) locus and another
      gene, either BCL or MYC, are common events in B-cell lymphoma. Occasionally, two
      IG loci, one with BCL and the other with MYC, are simultaneously involved; such
      cases are classified as double-hit (DH) lymphomas. These tumors often show
      intermediate histologic features between those of diffuse large B-cell lymphoma
      and those of Burkitt lymphoma. Patients with DH lymphoma have a poor prognosis.
      Rarely, lymphomas in which three IG loci are simultaneously involved with two
      different BCL genes and MYC have been reported. These cases are classified as
      triple-hit lymphomas; virtually all these are aggressive tumors with an even
      worse prognosis. We present here a unique case of follicular lymphoma (FL) with
      rearranged BCL2, BCL6, and BCL1 (also known as CCND1) genes. Lymphoma cells at
      first clinical relapse had a complex karyotype that included a t(3;22)(q27;q11)
      and t(14;18)(q32;q21). About 15 years after initial diagnosis, the lymphoma cells
      showed clonal cytogenetic evolution and acquired a t(11;14)(q13;q32). This
      article is the first case report of a low grade B-cell lymphoma that had three
      lymphoma-associated reciprocal translocations not involving MYC and that had a
      long indolent clinical course. 

PMID- 25953461
TI  - A role for epigenetics in the formation of chromosome translocations in acute
      leukemia.
AB  - In general, the field of cancer genetics seems to have shifted its focus from
      cancer-associated genes to cancer-associated epigenetic activity. An abundance of
      evidence suggests that epigenetic malfunction, such as aberrant histone
      modification, and altered DNA methylation, is at the root of much, if not most
      aberrant gene expression associated with cancer. However, a role for epigenetics
      in physical DNA changes, such as chromosome rearrangements, is less obvious, and
      certainly less well understood. A growing body of evidence suggests that
      epigenetics may play a role in many of the steps of aberrant chromosome
      recombination, especially chromosome translocations, associated with cancers such
      as acute leukemias. 

PMID- 25953462
TI  - Prognostic value of chromosomal translocations in small-bowel diffuse large B
      cell lymphoma.
AB  - AIMS: The objective of this study was to investigate the incidence and clinical
      significance of lymphoma-associated chromosomal translocations, particularly
      those involving the immunoglobulin heavy chain gene (IGH) locus, in patients with
      small-bowel diffuse large B-cell lymphoma (DLBCL). METHODS AND RESULTS:
      Translocations involving IGH, bcl-6, MYC and bcl-2 were investigated with
      interphase fluorescence in-situ hybridization on paraffin-embedded tissues in 35
      patients with primary small-bowel DLBCL, and the overall survival (OS) and
      progression-free survival (PFS) rates were evaluated with the Kaplan-Meier
      method. Translocations involving IGH, bcl-6, MYC and bcl-2 were detected in 23
      (70%), 12 (36%), eight (24%) and six (18%) of 33 cases, respectively. The
      patients with IGH translocations showed less frequent relapse or progression of
      lymphoma (17%) than those without (60%, P = 0.034). Univariate analyses
      demonstrated that young age, a low international prognostic index, translocations
      involving IGH, extra copies of MALT1/bcl-2 and bcl-6 immunoexpression were
      significantly associated with better OS and PFS. Cox multivariate analysis
      revealed translocations involving IGH to constitute an independent prognostic
      factor for better PFS, but not better OS. CONCLUSIONS: Translocations involving
      IGH are frequent in cases of small-bowel DLBCL. These translocations may be
      predictive of a favourable clinical course.

PMID- 25953463
TI  - Unnoticed, Untapped, and Underappreciated: Clients' Perceptions of their Public
      Defenders.
AB  - The challenge of providing high-quality public defense services continues to be a
      concern at federal, state, and local levels. Some scholars have alluded to a
      potential solution in client-centered representation, but research in this area
      is sparse at best. Such a lack of understanding leaves in its place speculation,
      particularly as to the potential importance of client perceptions in shaping
      broader system legitimacy. To fill this gap and create an empirical platform for
      future research, an exploratory pilot study was launched with the Hamilton
      County, Ohio Public Defender's Office, which used mixed methodologies to assess
      client attitudes toward public defenders as a potential resource for aiding the
      improvement of indigent representation. Findings from this pilot study suggest
      that there are five factors a public defense attorney should address that may
      prove to be very important in obtaining client satisfaction and cooperation:
      engaging the client for input, listening to the client, examining the
      prosecutor's evidence, focusing on the client's case during meetings, and
      informing the client of potential consequences. Implications for practice and
      future research are discussed.

PMID- 25953464
TI  - Human Adipose Stem Cells: From Bench to Bedside.
AB  - Stem cell-based therapies for repair and regeneration of different tissues are
      becoming more important in the treatment of several diseases. Adult stem cells
      currently symbolize the most available source of cell progenitors for tissue
      engineering and repair and can be harvested using minimally invasive procedures.
      Moreover, mesenchymal stem cells (MSCs), the most widely used stem cells in stem
      cell-based therapies, are multipotent progenitors, with capability to
      differentiate into cartilage, bone, connective, muscle, and adipose tissue. So
      far, bone marrow has been regarded as the main source of MSCs. To date, human
      adult adipose tissue may be the best suitable alternative source of MSCs. Adipose
      stem cells (ASCs) can be largely extracted from subcutaneous human adult adipose
      tissue. A large number of studies show that adipose tissue contains a
      biologically and clinically interesting heterogeneous cell population called
      stromal vascular fraction (SVF). The SVF may be employed directly or cultured for
      selection and expansion of an adherent population, so called adipose-derived stem
      cells (ASCs). In recent years, literature based on data related to SVF cells and
      ASCs has augmented considerably: These studies have demonstrated the efficacy and
      safety of SVF cells and ASCs in vivo in animal models. On the basis of these
      observations, in several countries, various clinical trials involving SVF cells
      and ASCs have been permitted. This review aims at summarizing data regarding
      either ASCs cellular biology or ASCs-based clinical trials and at discussing the
      possible future clinical translation of ASCs and their potentiality in cell-based
      tissue engineering. 

PMID- 25953465
TI  - Caring for the cardio-oncology patient: straining to foresee the future.

PMID- 25953466
TI  - More than just words.

PMID- 25953467
TI  - Advanced cardiac sonographer: a reality at last.

PMID- 25953468
TI  - Real time atherosclerosis assessment in outpatient cardiology practice along with
      cardiovascular risk assessment and physician patient communication: a three
      pronged approach for patient risk evaluation, education, and treatment.

PMID- 25953469
TI  - Effects of gas composition on the delivered tidal volume of the Avance
      Carestation.
AB  - BACK GROUND: Measurements with various flowmeters are affected by changes in gas
      mixture density. The Avance Carestation incorporates ventilator feedback
      controlled by a built-in flowmeter with a variable orifice sensor. We
      hypothesised that changes in the composition of delivered gas may cause changes
      in the delivered tidal volume by affecting the flow measurement unless
      appropriate corrections are made. METHODS: We used 100 % O2, 40 % O2 in N2 and 40
      % O2 in N2O as carrier gases with/without sevoflurane and desflurane. We measured
      delivered tidal volume using the FlowAnalyzerTM PF 300 calibrated with the
      corresponding gas mixtures during volume control ventilation with 500-ml tidal
      volume using the Avance Carestation connected to a test lung. RESULTS: Change of
      carrier gas and addition of sevoflurane and desflurane significantly altered
      delivered tidal volume. Desflurane 6 % reduced delivered tidal volume by 7.6, 3.6
      and 16 % of the pre-set volume at 100 % O2, 40 % O2 in N2 and 40 % O2 in N2O,
      respectively. Importantly, the Carestation panel indicator did not register these
      changes in measured expired tidal volume. Ratios of delivered tidal volume to 500
      ml correlated inversely with the square root of the delivered gas density.
      CONCLUSIONS: These results support our hypothesis and suggest that changing gas
      composition may alter delivered tidal volume of anesthesia machines with built-in
      ventilators that are feedback-controlled by uncorrected flowmeters due to changes
      in gas mixture density.

PMID- 25953470
TI  - Tailored stromal expansion with a refractive lenticule for crosslinking the
      ultrathin cornea.
AB  - We describe a technique for stromal expansion of thin and ultrathin corneas in
      keratoconus patients that uses refractive stromal lenticules of patients having
      small-incision lenticule extraction for myopic correction. The stromal lenticule
      is placed and spread over the host cornea following epithelial debridement so the
      thickest area of the 6.2 mm diameter lenticule corresponds to the thinnest area
      of the cone. The remaining collagen crosslinking (CXL) procedure is carried out
      in a routine manner. We believe tailored stromal expansion is a safe and
      effective technique for performing CXL in patients with thin corneas.

PMID- 25953471
TI  - Corneal ectasia 6.5 months after small-incision lenticule extraction.
AB  - Our case involves a 19-year-old patient with forme fruste keratoconus. Small
      incision lenticule extraction was performed, and 6.5 months after surgery,
      corneal ectasia was diagnosed. Preoperatively, the minimum central corneal
      thickness was 546 MUm in the right eye and 542 MUm in the left eye; the
      refractive correction was -6.75 -1.00 * 45 and -6.75 -0.75 * 140, respectively;
      the lenticular thickness was 137 MUm and 135 MUm, respectively. At 6.5 months,
      ectasia was diagnosed based on anterior and posterior surface keratometry of
      38.4/39.5 diopters (D) and -6.3/-6.8 D, respectively, in the right eye and
      38.6/40.8 D and -7.1/-6.6 D, respectively, in the left eye. The keratometry
      increased gradually and the corneal thickness decreased after surgery, and these
      trends continued during the 13-month follow-up. This report documents corneal
      ectasia as a complication of small-incision lenticule extraction and highlights
      the importance of preoperative evaluation and the need for long-term follow-up.

PMID- 25953472
TI  - Intraindividual comparative analysis of capsule opacification after implantation
      of 2 single-piece hydrophobic acrylic intraocular lenses models: Three-year
      follow-up.
AB  - PURPOSE: To compare the 3-year postoperative anterior (ACO) and posterior (PCO)
      capsule opacification and the level of anterior capsule retraction after
      implantation of 2 single-piece hydrophobic acrylic intraocular lens (IOL) models.
      SETTING: Hospital of St. John of God, Vienna, Austria. DESIGN: Comparative
      randomized controlled double-blind clinical trial. METHODS: Eyes with bilateral
      cataract were evaluated. Each patient had an Acrysof SA60AT (interrupted optic
      edge) IOL implanted in 1 eye (Group A) and a Tecnis ZCB00 (continuous optic edge)
      IOL implanted in the fellow eye (Group B). One and 3 years postoperatively, PCO
      was evaluated using Evaluation of Posterior Capsule Opacification software and
      the ACO level and capsule-retraction level were evaluated and graded
      subjectively. RESULTS: The study evaluated 100 eyes of 50 patients ranging from
      61 to 80 years. Postoperatively, there were no statistically significant
      differences in PCO between Group A and Group B at 1 year (0.06 +/- 0.12 [SD] and
      0.07 +/- 0.13, respectively; P = 4.35) or 3 years (0.23 +/- 0.36 and 0.22 +/-
      0.32, respectively; P = .66). In Group A and Group B, ACO was present in 18.0% of
      eyes and 2.7% of eyes, respectively, at 1 year (P = .03) and in 92.0% and 24.0%,
      respectively, at 3 years (P < .01). Capsule phimosis (18.0% at 1 year; 30.0% at 3
      years) and glistenings (66.0% at 1 year; 86.0% at 3 years) were observed in Group
      A only. CONCLUSION: Both IOLs had similarly low PCO rates 3 years
      postoperatively, although more ACO and capsule retraction were observed in eyes
      with the interrupted optic edge IOL.

PMID- 25953473
TI  - Changes in straylight and densitometry values after corneal collagen
      crosslinking.
AB  - PURPOSE: To evaluate the change in backward-directed and forward-directed corneal
      straylight in eyes after corneal collagen crosslinking (CXL) and its correlation
      with corrected distance visual acuity (CDVA) and changes in corneal topography.
      SETTING: Department of Ophthalmology, Medical University of Vienna, Vienna,
      Austria. DESIGN: Retrospective cohort study. METHODS: Following the Dresden
      protocol, corneal CXL was performed in eyes with progressive keratoconus. Corneal
      light scattering was evaluated using densitometry measurements from different
      corneal layers and zones obtained using Scheimpflug tomography (Pentacam HR).
      Retinal straylight values were measured using the C-Quant device. The CDVA was
      recorded during each follow-up examination. Changes in corneal topography were
      measured using Scheimpflug tomography. RESULTS: The study evaluated 31 eyes of 31
      patients. The mean densitometry of different corneal layers and in 3 different
      zones increased 3 months postoperatively and decreased thereafter. The mean
      densitometry in the 0.0 to 2.0 mm zone remained statistically significantly
      elevated after 12 months (P < .05). The mean preoperative retinal straylight was
      1.14 log(s) +/- 0.28 (SD). The mean straylight peaked after 1 month and then
      decreased continuously but remained elevated after 1 year at 1.26 +/- 0.21
      log(s). There was an increase in CDVA and flattening of the steepest keratometry
      (K) value (maximum K). Eyes with the greatest maximum K reduction also had the
      highest densitometry values. CONCLUSIONS: Crosslinking-induced stromal changes
      resulted in an increase in densitometry, especially in the anterior stroma of the
      central (0.0 to 2.0 mm) zone. These changes correlated with an increase in
      retinal straylight but not with the postoperative CDVA values.

PMID- 25953474
TI  - Corneal changes with accommodation using dual Scheimpflug photography.
AB  - PURPOSE: To assess whether corneal parameters and aberrations are affected by
      accommodation. SETTING: Optics Department, University of Valencia, Valencia,
      Spain. DESIGN: Prospective cross-sectional study. METHODS: The Galilei G4 dual
      Scheimpflug device was used to obtain data on the anterior and posterior axial
      curvatures, total corneal power (TCP), and corneal pachymetry from 3 corneal
      zones (central: 0.0 up to 4.0 mm; paracentral or mid: 4.0 up to 7.0 mm;
      peripheral: 7.0 up to 10.0 mm) in young emmetropic eyes in the unaccommodated and
      4 accommodated states (from -1.0 to -4.0 diopters [D] in 1.0 D steps). The 2nd-,
      3rd-, and 4th-order aberrations as well as the root mean square (RMS) were also
      determined for the entire cornea at the same accommodative demands. RESULTS: The
      study evaluated 7 subjects (12 eyes). No significant changes in any measured
      parameter were found during accommodation for any corneal zone (P > .05).
      Statistically significant differences were found in the various corneal zones
      when it was assumed they were constant with accommodation (P < .01). A stable
      linear trend with accommodation was also found for corneal aberrations, although
      individual variations existed because of the high standard deviation values.
      CONCLUSION: Different parameters in various zones of the cornea as well as
      corneal aberrations were stable during accommodation.

PMID- 25953476
TI  - Asymptotically Correct Standardization of Person-Fit Statistics Beyond
      Dichotomous Items.
AB  - The [Formula: see text] statistic (Drasgow et al. in Br J Math Stat Psychol 38:67
      86, 1985) is one of the most popular person-fit statistics (Armstrong et al. in
      Pract Assess Res Eval 12(16):1-10, 2007). Snijders (Psychometrika 66:331-342,
      2001) derived the asymptotic null distribution of [Formula: see text] when the
      examinee ability parameter is estimated. He also suggested the [Formula: see
      text] statistic, which is the asymptotically correct standardized version of
      [Formula: see text]. However, Snijders (Psychometrika 66:331-342, 2001) only
      considered tests with dichotomous items. In this paper, the asymptotic null
      distribution of [Formula: see text] is derived for mixed-format tests (those that
      include both dichotomous and polytomous items). The asymptotically correct
      standardized version of [Formula: see text], which can be considered as the
      extension of [Formula: see text] to such tests, is suggested. The Type I error
      rate and power of the suggested statistic are examined from several simulated
      datasets. The suggested statistic is computed using a real dataset. The suggested
      statistic appears to be a satisfactory tool for assessing person fit for mixed
      format tests.

PMID- 25953477
TI  - An Improved Correction for Range Restricted Correlations Under Extreme, Monotonic
      Quadratic Nonlinearity and Heteroscedasticity.
AB  - Standardized tests are frequently used for selection decisions, and the
      validation of test scores remains an important area of research. This paper
      builds upon prior literature about the effect of nonlinearity and
      heteroscedasticity on the accuracy of standard formulas for correcting
      correlations in restricted samples. Existing formulas for direct range
      restriction require three assumptions: (1) the criterion variable is missing at
      random; (2) a linear relationship between independent and dependent variables;
      and (3) constant error variance or homoscedasticity. The results in this paper
      demonstrate that the standard approach for correcting restricted correlations is
      severely biased in cases of extreme monotone quadratic nonlinearity and
      heteroscedasticity. This paper offers at least three significant contributions to
      the existing literature. First, a method from the econometrics literature is
      adapted to provide more accurate estimates of unrestricted correlations. Second,
      derivations establish bounds on the degree of bias attributed to quadratic
      functions under the assumption of a monotonic relationship between test scores
      and criterion measurements. New results are presented on the bias associated with
      using the standard range restriction correction formula, and the results show
      that the standard correction formula yields estimates of unrestricted
      correlations that deviate by as much as 0.2 for high to moderate selectivity.
      Third, Monte Carlo simulation results demonstrate that the new procedure for
      correcting restricted correlations provides more accurate estimates in the
      presence of quadratic and heteroscedastic test score and criterion relationships.

PMID- 25953478
TI  - Authors' response: Long-term lung function in postinfectious bronchiolitis
      obliterans.

PMID- 25953479
TI  - Use of Quilting Sutures During Abdominoplasty to Prevent Seroma Formation: Are
      They Really Effective?
AB  - BACKGROUND: Abdominoplasty surgery is one of the most popular cosmetic procedures
      performed in plastic surgery. As with any surgical procedure, it is associated
      with risks and complications, primarily that of seroma formation. Quilting
      sutures are a recent development in abdominoplasty surgery that aim to prevent
      the incidence of seroma. OBJECTIVES: The aim of this article was to assess the
      effectiveness of quilting suturing in the prevention of seroma formation.
      METHODS: In our retrospective clinical study, 414 female patients underwent
      abdominoplasty surgery with liposculpture contouring. The patients were divided
      in to three groups. The first group, comprising of 100 patients, were fitted with
      two drains postoperatively and no quilting sutures. The second group of 226
      patients underwent quilting suturing in addition to receiving two drains. And the
      final group of 88 patients also underwent quilting suturing, but received only
      one drain. Post-operative seroma diagnosis was confirmed with the presence of
      clinical signs and symptoms. RESULTS: The data was analysed using Fisher's exact
      test. With P < .000, we rejected our null hypothesis that there is no difference
      in results between the procedure with sutures and that without sutures. We
      calculated that the probability of having seroma with sutures to be <0.02. In
      contrast, abstinence from quilting sutures resulted in a 12% risk of seroma
      formation. CONCLUSIONS: The use of quilting sutures is a significantly effective
      measure for the prevention of seroma formation. LEVEL OF EVIDENCE: 4 Therapeutic.

PMID- 25953480
TI  - 5-year study of a polyacrylamide hydrogel-based filler for rehabilitation of HIV
      related facial lipoatrophy.
AB  - BACKGROUND: Lipoatrophy of the face negatively impacts the quality of life and
      body image of individuals on antiretroviral therapy. Facial fillers can minimize
      the stigma associated with the human immonodeficiency virus (HIV). OBJECTIVES: In
      this 5-year follow-up study, the author assessed the safety and efficacy of a
      permanent, non-biodegradable, polyacrylamide hydrogel for facial volume
      restoration, and compared the results with those of a previous 18-month follow-up
      study. METHODS: Thirty-one HIV-positive individuals, initially enrolled in the
      study between January 2008 and January 2009, received treatment of facial wasting
      by injection of the polyacrylamide gel until complete volume restoration was
      achieved. Asepsis rules were strictly observed before and during each injection
      session. Patients evaluated their aesthetic outcomes on a visual analog scale.
      RESULTS: Patient satisfaction was high. There was no occurrence of local
      infection, foreign-body reaction, or product during the 5 years of follow-up.
      Small, palpable, nonvisible nodules were recorded in nine cases. It appears that
      these same nodules were present in the 18-month study. It is believed that the
      nodules were caused by overfilling in the same site. CONCLUSIONS: As supported by
      the initial 18-month study, polyacrylamide hydrogel filler appears safe and
      effective for the treatment of HIV-related lipoatrophy. With strict observation
      of asepsis rules and patient adherence to posttreatment instructions, this filler
      can be ideal for treating facial wasting in patients with HIV. LEVEL OF EVIDENCE:
      3 Therapeutic.

PMID- 25953481
TI  - Effects of vitamin D supplementation during pregnancy on neonatal vitamin D and
      calcium concentrations: a systematic review and meta-analysis.
AB  - We conducted a meta-analysis to review the effects of vitamin D supplementation
      during pregnancy on neonatal 25-hydroxyvitamin D (25(OH)D) and calcium
      concentrations. Randomized controlled trials that supplemented subjects with
      vitamin D2 or D3 during pregnancy and reported cord blood 25(OH)D or calcium
      concentrations were included. A random-effect model was used to pool the data.
      Subgroup analyses were performed to explore the sources of heterogeneity. We
      searched PubMed, Web of Science, and Cochrane Library for relevant publications.
      Among 1768 publications identified by our search strategy, 13 studies met our
      inclusion criteria. Cord blood 25(OH)D concentration was significantly increased
      by maternal vitamin D supplementation (mean difference, 22.48 nmol/L; 95%
      confidence interval, 15.90-29.06 nmol/L) with high heterogeneity (I2 = 98.8%, P <
      .0001). No effects on cord blood calcium concentration was reported (mean
      difference, 0.05 mmol/L; 95% confidence interval, -0.04-0.13 mmol/L).
      Supplementation regimens and the different control groups may be the major
      sources of heterogeneity. Vitamin D supplementation during pregnancy can improve
      cord blood 25(OH)D concentration in women with low 25(OH)D concentration, but
      does not affect cord blood calcium concentration. Future researches are needed to
      evaluate the effect of maternal vitamin D supplementation in women with a normal
      25(OH)D concentration and explore the combined effects of vitamin D, calcium, and
      multivitamins.

PMID- 25953482
TI  - A model for the coupled disease dynamics of HIV and HSV-2 with mixing among and
      between genders.
AB  - Evidence indicates that those with genital herpes (HSV-2) infections have greater
      risks of infection by HIV; and, once co-infected, are more likely to transmit
      HIV. To better understand the interactions between HIV and HSV-2, we construct a
      mathematical model that describes the joint dynamics. A new feature of this model
      is the inclusion of both heterosexual and homosexual interactions. We derive and
      interpret the basic and invasion reproduction numbers for HIV and HSV-2 using the
      approach of next-generation matrices. We then perform scenario analyses and
      conduct a sensitivity analysis to investigate the impact of the model parameters
      on the reproduction numbers and disease prevalences. We conclude that homosexual
      transmission drastically changes the disease prevalences; hence, it is important
      to account for this interaction as models that ignore homosexuality may greatly
      underestimate the disease burden. 

PMID- 25953483
TI  - Management and outcome of mechanically ventilated patients after cardiac arrest.
AB  - INTRODUCTION: The aim of this study was to describe and compare the changes in
      ventilator management and complications over time, as well as variables
      associated with 28-day hospital mortality in patients receiving mechanical
      ventilation (MV) after cardiac arrest. METHODS: We performed a secondary analysis
      of three prospective, observational multicenter studies conducted in 1998, 2004
      and 2010 in 927 ICUs from 40 countries. We screened 18,302 patients receiving MV
      for more than 12 hours during a one-month-period. We included 812 patients
      receiving MV after cardiac arrest. We collected data on demographics, daily
      ventilator settings, complications during ventilation and outcomes. Multivariate
      logistic regression analysis was performed to calculate odds ratios, determining
      which variables within 24 hours of hospital admission were associated with 28-day
      hospital mortality and occurrence of acute respiratory distress syndrome (ARDS)
      and pneumonia acquired during ICU stay at 48 hours after admission. RESULTS:
      Among 812 patients, 100 were included from 1998, 239 from 2004 and 473 from 2010.
      Ventilatory management changed over time, with decreased tidal volumes (VT)
      (1998: mean 8.9 (standard deviation (SD) 2) ml/kg actual body weight (ABW), 2010:
      6.7 (SD 2) ml/kg ABW; 2004: 9 (SD 2.3) ml/kg predicted body weight (PBW), 2010:
      7.95 (SD 1.7) ml/kg PBW) and increased positive end-expiratory pressure (PEEP)
      (1998: mean 3.5 (SD 3), 2010: 6.5 (SD 3); P <0.001). Patients included from 2010
      had more sepsis, cardiovascular dysfunction and neurological failure, but 28-day
      hospital mortality was similar over time (52% in 1998, 57% in 2004 and 52% in
      2010). Variables independently associated with 28-day hospital mortality were:
      older age, PaO2 <60 mmHg, cardiovascular dysfunction and less use of sedative
      agents. Higher VT, and plateau pressure with lower PEEP were associated with
      occurrence of ARDS and pneumonia acquired during ICU stay. CONCLUSIONS:
      Protective mechanical ventilation with lower VT and higher PEEP is more commonly
      used after cardiac arrest. The incidence of pulmonary complications decreased,
      while other non-respiratory organ failures increased with time. The application
      of protective mechanical ventilation and the prevention of single and multiple
      organ failure may be considered to improve outcome in patients after cardiac
      arrest.

PMID- 25953485
TI  - Compartmentalized and contrasted response of ectomycorrhizal and soil fungal
      communities of Scots pine forests along elevation gradients in France and Spain.
AB  - Fungi are principal actors of forest soils implied in many ecosystem services and
      the mediation of tree's responses. Forecasting fungal responses to environmental
      changes is necessary for maintaining forest productivity, although our partial
      understanding of how abiotic and biotic factors affect fungal communities is
      restricting the predictions. We examined fungal communities of Pinus sylvestris
      along elevation gradients to check potential responses to climate change
      associated factors. Fungi of roots and soils were analysed at a regional scale,
      by using a high-throughput sequencing approach. Overall soil fungal richness
      increased with pH, whereas it did not vary with climate. However, when
      representative sub-assemblages, i.e. Ascomycetes/Basidiomycetes, and families
      were analysed, they differentially answered to climatic and edaphic variables.
      This response was dependent on where they settled, i.e. soil versus roots, and/or
      on their lifestyle, i.e. mycorrhizal or not, suggesting different potential
      functional weights within the community. Our results revealed a highly
      compartmentalized and contrasted response of fungal communities in forest soils.
      The different response of fungal sub-assemblages indicated a range of possible
      selective direct and indirect (i.e. via host) impacts of climatic variations on
      these communities, of unknown functional consequences, that helps in
      understanding potential fungal responses under future global change scenarios. 

PMID- 25953484
TI  - Outer membrane vesicles of Tannerella forsythia: biogenesis, composition, and
      virulence.
AB  - Tannerella forsythia is the only 'red-complex' bacterium covered by an S-layer,
      which has been shown to affect virulence. Here, outer membrane vesicles (OMVs)
      enriched with putative glycoproteins are described as a new addition to the
      virulence repertoire of T. forsythia. Investigations of this bacterium are
      hampered by its fastidious growth requirements and the recently discovered
      mismatch of the available genome sequence (92A2 = ATCC BAA-2717) and the widely
      used T. forsythia strain (ATCC 43037). T. forsythia was grown anaerobically in
      serum-free medium and biogenesis of OMVs was analyzed by electron and atomic
      force microscopy. This revealed OMVs with a mean diameter of ~100 nm budding off
      from the outer membrane while retaining the S-layer. An LC-ESI-TOF/TOF proteomic
      analysis of OMVs from three independent biological replicates identified 175
      proteins. Of these, 14 exhibited a C-terminal outer membrane translocation signal
      that directs them to the cell/vesicle surface, 61 and 53 were localized to the
      outer membrane and periplasm, respectively, 22 were predicted to be
      extracellular, and 39 to originate from the cytoplasm. Eighty proteins contained
      the Bacteroidales O-glycosylation motif, 18 of which were confirmed as
      glycoproteins. Release of pro-inflammatory mediators from the human monocytic
      cell line U937 and periodontal ligament fibroblasts upon stimulation with OMVs
      followed a concentration-dependent increase that was more pronounced in the
      presence of soluble CD14 in conditioned media. The inflammatory response was
      significantly higher than that caused by whole T. forsythia cells. Our study
      represents the first characterization of T. forsythia OMVs, their proteomic
      composition and immunogenic potential.

PMID- 25953487
TI  - Heterotopic bone with rotator cuff tear: a case report and review of the
      literature.

PMID- 25953486
TI  - Osteochondritis dissecans of the humeral capitellum: reliability of four
      classification systems using radiographs and computed tomography.
AB  - BACKGROUND: The radiographic appearance of osteochondritis dissecans (OCD) of the
      humeral capitellum varies according to the stage of the lesion. It is important
      to evaluate the stage of OCD lesion carefully to guide treatment. We compared the
      interobserver reliability of currently used classification systems for OCD of the
      humeral capitellum to identify the most reliable classification system. METHODS:
      Thirty-two musculoskeletal radiologists and orthopaedic surgeons specialized in
      elbow surgery from several countries evaluated anteroposterior and lateral
      radiographs and corresponding computed tomography (CT) scans of 22 patients to
      classify the stage of OCD of the humeral capitellum according to the
      classification systems developed by (1) Minami, (2) Berndt and Harty, (3) Ferkel
      and Sgaglione, and (4) Anderson on a Web-based study platform including a Digital
      Imaging and Communications in Medicine viewer. Magnetic resonance imaging was not
      evaluated as part of this study. We measured agreement among observers using the
      Siegel and Castellan multirater kappa. RESULTS: All OCD classification systems,
      except for Berndt and Harty, which had poor agreement among observers (kappa =
      0.20), had fair interobserver agreement: kappa was 0.27 for the Minami, 0.23 for
      Anderson, and 0.22 for Ferkel and Sgaglione classifications. The Minami
      Classification was significantly more reliable than the other classifications (P
      < .001). CONCLUSIONS: The Minami Classification was the most reliable for
      classifying different stages of OCD of the humeral capitellum. However, it is
      unclear whether radiographic evidence of OCD of the humeral capitellum, as
      categorized by the Minami Classification, guides treatment in clinical practice
      as a result of this fair agreement.

PMID- 25953488
TI  - Does resident involvement have an impact on postoperative complications after
      total shoulder arthroplasty? An analysis of 1382 cases.
AB  - BACKGROUND: The impact of resident involvement on total shoulder arthroplasty
      (TSA) complication rate is unknown. The purpose of this study was to assess
      whether resident involvement in TSA is associated with 30-day complication rates.
      METHODS: The American College of Surgeons National Surgical Quality Improvement
      Program database was searched for all patients who underwent TSA between 2005 and
      2012. Data were extracted for patient preoperative demographics, intraoperative
      variables, resident involvement in surgery, and 30-day postoperative
      complications. Resident and nonresident cases were grouped by a matched
      propensity score analysis. Univariate and multivariate analysis was performed to
      assess the effect of resident involvement on postoperative complications.
      RESULTS: We analyzed 1382 patients who underwent primary TSA, with matched groups
      of 691 with and 691 without resident involvement. The overall rate of 30-day
      complications was 2.60% in TSAs in which a resident was involved compared with
      3.91% when no resident was involved (P = .173). Operative time and hospital stay
      were shorter in cases in which a resident was present (P = .002 and P < .001,
      respectively). Independent risk factors significantly associated with TSA
      complications identified by multivariate regression were higher patient age,
      higher American Society of Anesthesiologists classification, congestive heart
      failure, insulin-dependent diabetes, and peripheral vascular disease. CONCLUSION:
      Resident involvement in TSA procedures is not a risk factor for 30-day
      complications. Patient factors including increased age, diabetes, and cardiac
      disease are risk factors for TSA complications. This information can be used in
      preoperative counseling to reassure patients about safety of resident involvement
      in TSA and to optimize patient comorbidities before surgery.

PMID- 25953489
TI  - Effects of humeral component retroversion on functional outcomes in reverse total
      shoulder arthroplasty for cuff tear arthropathy.
AB  - BACKGROUND: The currently recommended 0 degrees  to 30 degrees  humeral component
      retroversion angle for reverse total shoulder arthroplasty (RTSA) is based on
      expert opinion rather than anatomical or clinical evidence. METHODS: Sixty-two
      patients who underwent RTSA for cuff tear arthropathy were reviewed
      retrospectively. The humeral component was inserted with 20 degrees  retroversion
      in 30 patients (group A) and with 0 degrees  retroversion in 32 (group B). The
      mean age at the time of operation was 66.2 years and 68.9 years, and the mean
      follow-up period was 43.3 months and 38.4 months in groups A and B, respectively.
      RESULTS: At the last follow-up, external rotation at the side was 47.2 degrees 
      +/- 8.4 degrees  in group A and 43.9 degrees  +/- 7.0 degrees  in group B,
      whereas internal rotation to the posterior was L3 and L2, respectively (P = .102
      and P = .092). The ranges of motion between the 2 groups at the last follow-up
      were not significantly different. Most daily movements related to activities of
      daily living showed no significant differences between the 2 groups, with the
      exception of back washing/back doing up bra (1.5 +/- 1.2 in group A vs 2.1 +/-
      0.8 in group B of 3 points, P = .026). CONCLUSIONS: Range of motion after RTSA
      did not significantly differ between 20 degrees  and 0 degrees  humeral component
      retroversion angle. Most daily movements did not differ between the 2 groups, but
      patients in the 0 degrees  retroversion angle group scored better on activities
      related to internal rotation.

PMID- 25953490
TI  - Argon Cluster Sputtering Source for ToF-SIMS Depth Profiling of Insulating
      Materials: High Sputter Rate and Accurate Interfacial Information.
AB  - The use of an argon cluster ion sputtering source has been demonstrated to
      perform superiorly relative to traditional oxygen and cesium ion sputtering
      sources for ToF-SIMS depth profiling of insulating materials. The superior
      performance has been attributed to effective alleviation of surface charging. A
      simulated nuclear waste glass (SON68) and layered hole-perovskite oxide thin
      films were selected as model systems because of their fundamental and practical
      significance. Our results show that high sputter rates and accurate interfacial
      information can be achieved simultaneously for argon cluster sputtering, whereas
      this is not the case for cesium and oxygen sputtering. Therefore, the
      implementation of an argon cluster sputtering source can significantly improve
      the analysis efficiency of insulating materials and, thus, can expand its
      applications to the study of glass corrosion, perovskite oxide thin film
      characterization, and many other systems of interest.

PMID- 25953491
TI  - Iron Fluoroanions and Their Clusters by Electrospray Ionization of a Fluorinating
      Ionic Liquid.
AB  - Metal fluoroanions are of significant interest for fundamental structure and
      reactivity studies and for making isotope ratio measurements that are free from
      isobaric overlap. Iron fluoroanions [FeF(4)](-) and [FeF(3)](-) were generated by
      electrospray ionization of solutions of Fe(III) and Fe(II) with the fluorinating
      ionic liquid 1-ethyl-3-methylimidazolium fluorohydrogenate [EMIm](+)[F(HF)(2.3)](
      ). Solutions containing Fe(III) salts produce predominately uncomplexed [FeF(4)](
      ) in the negative ion spectrum, as do solutions containing salts of Fe(II). This
      behavior contrasts with that of solutions of FeCl(3) and FeCl(2) (without
      [EMIm](+)[F(HF)(2.3)](-)) that preserve the solution-phase oxidation state by
      producing the gas-phase halide complexes [FeCl(4)](-) and [FeCl(3)](-),
      respectively. Thus, the electrospray-[EMIm](+)[F(HF)(2.3)](-) process is
      oxidative with respect to Fe(II). The positive ion spectra of Fe with
      [EMIm](+)[F(HF)(2.3)](-) displays cluster ions having the general formula
      [EMIm](+) (n+1)[FeF(4)](-) n, and DFT calculations predict stable complexes, both
      of which substantiate the conclusion that [FeF(4)](-) is present in solution
      stabilized by the imidazolium cation. The negative ion ESI mass spectrum of the
      Fe-ionic liquid solution has a very low background in the region of the [FeF(4)](
      ) complex, and isotope ratios measured for both [FeF(4)](-) and adventitious
      [SiF(5)](-) produced values in close agreement with theoretical values; this
      suggests that very wide isotope ratio measurements should be attainable with good
      accuracy and precision when the ion formation scheme is implemented on a
      dedicated isotope ratio mass spectrometer.

PMID- 25953492
TI  - Determination of nicotine and its metabolites accumulated in fish tissue using
      hydrophilic interaction liquid chromatography coupled with tandem mass
      spectrometry.
AB  - The determination of nicotine and its major metabolites (cotinine and anabasine)
      in fish tissue was performed using liquid chromatography and tandem mass
      spectrometry. Marine and freshwater fish were purchased from local grocery stores
      and were prepared based on a quick, easy, cheap, effective, rugged, and safe
      sample preparation protocol. To determine the highly polar compounds, hydrophilic
      interaction liquid chromatography was also used. There were modest suppressions
      on measured nicotine signals (10%) due to the matrix effects from marine fish but
      no obvious effects on freshwater fish signals. Method validation was incorporated
      with internal standards and carried out with matrix-matched calibration. The
      detection limits for nicotine, cotinine, and anabasine were 9.4, 3.0, and 1.5
      ng/g in fish, respectively. Precision was quite acceptable returning less than 8%
      RSD at low, medium, and high concentrations. Acceptable and reproducible
      extraction recoveries (70-120%) of all three compounds were achieved, except for
      anabasine at low concentration (61%). The method was then applied to define
      nicotine bioaccumulation in a fathead minnow model, which resulted in rapid
      uptake with steady state internal tissue levels, reached within 12 h. This
      developed method offers a fast, easy, and sensitive way to evaluate nicotine and
      its metabolite residues in fish tissues. 

PMID- 25953493
TI  - Long-term experience of hyperbaric oxygen therapy for refractory radio- or
      chemotherapy-induced haemorrhagic cystitis.
AB  - BACKGROUND: Radiotherapy and cyclophosphamide-induced haemorrhagic cystitis are
      rare but severe complications occurring in 3-6% of patients. Hyperbaric oxygen
      treatment (HBOT) has been demonstrated to be an effective treatment for
      haematuria not responding to conventional management. Only very few data exist
      for long-term follow-up after HBOT. METHODS: We retrospectively reviewed 15
      patients referred for HBOT for haemorrhagic cystitis (HC). HBOT was performed for
      130 min/day at a pressure of 2.4 atmospheres. We evaluated patient demographics,
      type of radio- and chemotherapy and characteristics of haematuria. The effect of
      HBOT was defined as complete or partial resolution of hematuria according to the
      RTOG/EORTC grade and Gray score. RESULTS: A total of 15 patients (12 after
      radiotherapy, two after chemotherapy and one patient with a combination of both)
      were treated with a median of 34 HBO treatments. Radiotherapy patients received
      primary, adjuvant, salvage and HDR radiotherapy (60 - 78 Gy) for prostate, colon
      or cervical cancer. The patient with combination therapy and both of the
      chemotherapy patients were treated with cyclophosphamide. First episodes of
      haematuria occurred at a median of 48 months after completion of initial therapy.
      The first HBOT was performed at a median of 11 months after the first episode of
      hematuria. After a median of a 68-month follow-up after HBOT, 80% experienced a
      complete resolution and two patients suffered a singular new minor haematuria (p
      < 0.00001). A salvage-cystectomy was necessary in one patient. No adverse effects
      were documented. CONCLUSIONS: Our experience indicate that HBOT is a safe and
      effective therapeutic option for treatment-resistant radiogenic and chemotherapy
      induced haemorrhagic cystitis. For a better evaluation prospective clinical
      trials are required.

PMID- 25953494
TI  - Comparison of shock wave therapy and nutraceutical composed of Echinacea
      angustifolia, alpha lipoic acid, conjugated linoleic acid and quercetin
      (perinerv) in patients with carpal tunnel syndrome.
AB  - Even though the initial treatment of carpal tunnel syndrome (CTS) is
      conservative, knowledge of the clinical effects of supplements and of some
      methods of physiotherapy is still preliminary. Many biological mechanisms can
      support the administration of shock wave therapy (ESWT) or of alpha lipoic acid
      (ALA) based nutraceutical, conjugated linoleic acid (GLA), anti-oxidants and
      Echinacea angustifolia for CTS. The shock waves reduce the nerve compression,
      produce an anti-inflammatory action, and accelerate the regeneration of
      neuropathy. ALA and GLA induce antioxidant protective actions, reduce
      inflammation, promote neuroregeneration, and decrease pain. The Echinacea
      modulates the endogenous cannabinoid system.The aim of study is to verify the
      efficiency of shock wave therapy versus nutraceutical composed of ALA, GLA, and
      Echinacea in CTS. Sixty patients were enrolled in this study and they were
      randomly assigned to one of two treatments. Both groups showed significant
      improvements in pain, symptoms' severity and functional scores, and
      electrodiagnostic results until the sixth month. We verified a trend to a better
      pain regression in the nutraceutical group. The presence of the medicinal
      Echinacea represents an added value to the antioxidant effect in ALA and GLA,
      which can justify this result. ESWT or the association of ALA, GLA, and Echinacea
      proved to be two effective treatments for controlling symptoms and improving the
      evolution of CTS. 

PMID- 25953495
TI  - Liver regeneration: A consequence of complex, well-orchestrated signals.

PMID- 25953496
TI  - Investigation of a recent rise of dual amantadine-resistance mutations in the
      influenza A M2 sequence.
AB  - BACKGROUND: The S31N amantadine-resistance mutation in the influenza A M2
      sequence currently occurs more frequently in nature than the S31 wild type.
      Overcoming the resistance of the S31N mutation is the primary focus of M2
      researchers who aim to develop novel antiviral therapies. Recent studies have
      noted a possible rise in frequency of the V27A/S31N double amantadine-resistance
      mutation in recent years. The purpose of this study is to investigate this recent
      rise in frequency of the double mutation and any possible bias of the other
      mutations toward co-occurrence with S31N or S31 strains. RESULTS: The primary
      dataset used for this study was comprised of 24,152 influenza A M2 channel
      sequences which were downloaded from UniProt. There is an increased frequency for
      the S31N/V27A dual AR mutation in recent years, especially in swine. A test for
      difference in two proportions indicates that the V27A mutation is co-occurring
      with S31N more often than expected (p-value<0.001) when considering individual
      amino acid frequencies. At the same time, the different propensities for the V27A
      as compared to the V27T dual mutant may reflect differences in viral fitness or
      protein energetics, and this information could be exploited to focus drug
      development so as to reduce further drug insensitivity. CONCLUSIONS: The
      development of the S31N/V27A variant in the Midwestern US swine may be a
      harbinger of novel human strain development. V27A/S31N is a possible path forward
      for the evolution of M2 which may convey a new level of drug resistance and
      should receive attention in drug design.

PMID- 25953497
TI  - Transient low-barrier hydrogen bond in the photoactive state of green fluorescent
      protein.
AB  - In this paper, we have analyzed the feasibility of spontaneous proton transfer in
      GFP at the Franck-Condon region directly after photoexcitation. Computation of a
      sizeable portion of the potential energy surface at the Franck-Condon region of A
      the structure shows the process of proton transfer to be unfavorable by 3 kcal
      mol(-1) in S1 if no further structural relaxation is permitted. The ground
      vibrational state is found to lie above the potential energy barrier of the
      proton transfer in both S0 and S1. Expectation values of the geometry reveal that
      the proton shared between the chromophore and W22, and the proton shared between
      Ser205 and Glu222 are very close to the center of the respective hydrogen bonds,
      giving support to the claim that the first transient intermediate detected after
      photoexcitation (I0*) has characteristics similar to those of a low-barrier
      hydrogen bond [Di Donato et al., Phys. Chem. Chem. Phys., 2012, 13, 16295]. A
      quantum dynamical calculation of the evolution in the excited state shows an even
      larger probability of finding those two protons close to the center compared to
      in the ground state, but no formation of the proton-transferred product is
      observed. A QM/MM photoactive state geometry optimization, initiated using a
      configuration obtained by taking the A minimum and moving the protons to the
      product side, yields a minimum energy structure with the protons transferred and
      in which the His148 residue is substantially closer to the now anionic
      chromophore. These results indicate that: (1) proton transfer is not possible if
      structural relaxation of the surroundings of the chromophore is prevented; (2)
      protons H1 and H3 especially are found very close to the point halfway between
      the donor and acceptor after photoexcitation when the zero-point energy is
      considered; (3) a geometrical parameter exists (the His148-Cro distance) under
      which the structure with the protons transferred is not a minimum, and that, if
      included, should lead to the fluorescing I* structure. The existence of an
      oscillating stationary state between the reactants and products of the triple
      proton transfer reaction can explain the dual emission reported for the I0*
      intermediate of wtGFP.

PMID- 25953498
TI  - MALDI-TOF mass spectrometry following short incubation on a solid medium is a
      valuable tool for rapid pathogen identification from positive blood cultures.
AB  - INTRODUCTION: Rapid identification of the causative microorganism is a key
      element in appropriate antimicrobial therapy of bloodstream infections. Whereas
      traditional analysis of positive blood cultures requires subculture over at least
      16-24h prior to pathogen identification by, e.g. matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), sample
      preparation procedures enabling direct MALDI-TOF MS, i.e. without preceding
      subculture, are associated with additional effort and costs. Hence, we integrated
      an alternative MALDI-TOF MS approach in diagnostic routine using a short
      incubation on a solid medium. MATERIALS AND METHODS: Positive blood cultures were
      routinely plated on chocolate agar plates and incubated for 4h (37  degrees C, 5%
      CO2). Subsequently, MALDI-TOF MS using a Microflex LT instrument (Bruker
      Daltonics) and direct smear method was performed once per sample. For successful
      identification of bacteria at species level, score cut-off values were used as
      proposed by the manufacturer (>= 2.0) and in a modified form (>= 1.5 for MALDI
      TOF MS results referring to Gram-positive cocci and >= 1.7 for MALDI-TOF MS
      results referring to bacteria other than Gram-positive cocci). Further data
      analysis also included an assessment of the clinical impact of the MALDI-TOF MS
      result. RESULTS: Applying the modified score cut-off values, our approach led to
      an overall correct species identification in 69.5% with misidentification in 3.4%
      (original cut-offs: 49.2% and 1.8%, respectively); for Gram-positive cocci,
      correct identification in 68.4% (100% for Staphylococcus aureus and enterococci,
      80% for beta-hemolytic streptococci), for Gram-negative bacteria, correct
      identification in 97.6%. In polymicrobial blood cultures, in 72.7% one of the
      pathogens was correctly identified. Results were not reliable for Gram-positive
      rods and yeasts. The approach was easy to implement in diagnostic routine. In
      cases with available clinical data and successful pathogen identification, in
      51.1% our approach allowed an optimized treatment recommendation. CONCLUSION:
      MALDI-TOF MS following 4h pre-culture is a valuable tool for rapid pathogen
      identification from positive blood cultures, allowing easy integration in
      diagnostic routine and the opportunity of considerably earlier treatment
      adaptation.

PMID- 25953499
TI  - MicroRNAs in skin tissue engineering.
AB  - 35.2 million annual cases in the U.S. require clinical intervention for major
      skin loss. To meet this demand, the field of skin tissue engineering has grown
      rapidly over the past 40 years. Traditionally, skin tissue engineering relies on
      the "cell-scaffold-signal" approach, whereby isolated cells are formulated into a
      three-dimensional substrate matrix, or scaffold, and exposed to the proper
      molecular, physical, and/or electrical signals to encourage growth and
      differentiation. However, clinically available bioengineered skin equivalents
      (BSEs) suffer from a number of drawbacks, including time required to generate
      autologous BSEs, poor allogeneic BSE survival, and physical limitations such as
      mass transfer issues. Additionally, different types of skin wounds require
      different BSE designs. MicroRNA has recently emerged as a new and exciting field
      of RNA interference that can overcome the barriers of BSE design. MicroRNA can
      regulate cellular behavior, change the bioactive milieu of the skin, and be
      delivered to skin tissue in a number of ways. While it is still in its infancy,
      the use of microRNAs in skin tissue engineering offers the opportunity to both
      enhance and expand a field for which there is still a vast unmet clinical need.
      Here we give a review of skin tissue engineering, focusing on the important
      cellular processes, bioactive mediators, and scaffolds. We further discuss
      potential microRNA targets for each individual component, and we conclude with
      possible future applications.

PMID- 25953500
TI  - Evaluation of a simulation training programme for geriatric medicine.
AB  - BACKGROUND: geriatrics encompasses diverse medical, social and ethical challenges
      requiring a multidimensional, interdisciplinary approach. Recent reports have
      highlighted failings in the care of older people. It is therefore vital that
      trainees in geriatrics are afforded opportunities to develop skills in managing
      this complex population. Simulation has been adopted as a teaching tool in
      medicine; however, evidence for its use in geriatrics has been limited to small,
      single-site studies primarily involving role-play or discrete clinical skills
      training. METHODS: a standardised, two centre, multimodal, interprofessional,
      geriatrics simulation training programme was developed using curriculum-mapped
      scenarios in which the patient perspective was central. Simulation techniques
      used included high-fidelity patient manikins, actors with integrated clinical
      skills using part-task trainers and role-play exercises. A mixed-methods
      evaluation was used to analyse data from participants before and after training.
      RESULTS: eighty-nine candidates attended 12 similar courses over 2 years.
      Thematic analysis of candidate feedback was supportive of simulation as a useful
      tool, with benefits for both technical and non-technical skills. Candidates
      commented that simulation was a valuable training modality addressing curriculum
      areas rarely taught formally including continence assessment, end-of-life
      decisions and multidisciplinary situations. Quantitative analysis of pre- and
      post-course questionnaires revealed a significant improvement of self-reported
      confidence in managing geriatric scenarios (mean improvement 11.5%; P < 0.001).
      DISCUSSION: this study demonstrated the feasibility of a standardised simulation
      training programme across two sites in geriatrics. Simulation training affords
      situational learning without compromising patient safety and is an exciting and
      novel method of delivering teaching for geriatrics that could be integrated into
      national training curricula.

PMID- 25953501
TI  - Cell synchronization and isolation of chromosomes from Chinese fir root tips for
      flow cytometric analysis.
AB  - OBJECTIVES: To optimize treatment parameters to synchronize the cell cycle of
      Chinese fir root tip meristem cells. RESULTS: Optimal mitotic indices were
      achieved by treating seedlings with 1.25 mM hydroxyurea for 10 h, incubating for
      7 h without chemical treatment to release the hydroxyurea block, and then
      treating emerging roots with 0.05 % colchicine for 16 h. The mitotic index of
      synchronized Chinese fir root tips was over 30 %. Suspensions of intact
      chromosomes were prepared using a simple slicing procedure. CONCLUSIONS: The
      chromosome preparations were suitable for flow cytometric characterization and
      sorting. The chromosome peaks of the observed flow karyotype resembled the
      predicted flow karyotype calculated from the Chinese fir chromosome size.

PMID- 25953502
TI  - Secondary Defense Chemicals in Milkweed Reduce Parasite Infection in Monarch
      Butterflies, Danaus plexippus.
AB  - In tri-trophic systems, herbivores may benefit from their host plants in fighting
      parasitic infections. Plants can provide parasite resistance in two contrasting
      ways: either directly, by interfering with the parasite, or indirectly, by
      increasing herbivore immunity or health. In monarch butterflies, the larval diet
      of milkweed strongly influences the fitness of a common protozoan parasite. Toxic
      secondary plant chemicals known as cardenolides correlate strongly with parasite
      resistance of the host, with greater cardenolide concentrations in the larval
      diet leading to lower parasite growth. However, milkweed cardenolides may covary
      with other indices of plant quality including nutrients, and a direct
      experimental link between cardenolides and parasite performance has not been
      established. To determine if the anti-parasitic activity of milkweeds is indeed
      due to secondary chemicals, as opposed to nutrition, we supplemented the diet of
      infected and uninfected monarch larvae with milkweed latex, which contains
      cardenolides but no nutrients. Across three experiments, increased dietary
      cardenolide concentrations reduced parasite growth in infected monarchs, which
      consequently had longer lifespans. However, uninfected monarchs showed no
      differences in lifespan across treatments, confirming that cardenolide-containing
      latex does not increase general health. Our results suggest that cardenolides are
      a driving force behind plant-derived resistance in this system. 

PMID- 25953503
TI  - Mediolateral balance and gait stability in older adults.
AB  - Early detection of balance impairment is crucial to identify individuals who may
      benefit from interventions aimed to prevent falls, which is a major problem in
      aging societies. Since mediolateral balance deteriorates with aging, we proposed
      a mediolateral balance assessment (MELBA) tool that uses a CoM-tracking task of
      predictable sinusoidal and unpredictable multisine targets. This method has shown
      to be reliable and sensitive to aging effect, however, it is not known whether it
      can predict performance on common daily-life tasks such as walking. This study
      aimed to determine whether MELBA is an ecologically valid tool by correlating its
      outputs with a measure of mediolateral gait stability known to be predictive of
      falls. Nineteen community-dwelling older adults (72+/-5 years) tracked
      predictable and unpredictable target displacements at increasing frequencies with
      their CoM by shifting their weight sideward. Response delay (phase-shift) and
      amplitude difference (gain) between the CoM and target in the frequency domain
      were used to quantify performance. To assess gait stability, the local divergence
      exponent was calculated using mediolateral accelerations with an inertial sensor
      when walking on a treadmill (LDETR) and in daily-life (LDEDL) for one week.
      Pearson product-moment correlation analyses were performed to determine
      correlations between performance on MELBA tasks and LDE. Results show that phase
      shift bandwidth for the predictable target (range above -90 degrees ) was
      significantly correlated with LDETR whereas phase-shift bandwidth for the
      unpredictable target was significantly correlated with LDEDL. In conclusion MELBA
      is an ecologically valid tool for mediolateral balance assessment in community
      dwelling older adults who exhibit subtle balance impairments. 

PMID- 25953504
TI  - Free-living activity counts-derived breaks in sedentary time: Are they real
      transitions from sitting to standing?
AB  - BACKGROUND: Previous research has demonstrated a link between free-living
      accelerometer-measured breaks in sedentary time and health related variables.
      Breaks in sedentary time are typically inferred from time-stamped accelerometer
      data indicating a transition from lack of movement (recording of <100 activity
      counts/min) to relatively more movement (>=100 activity counts/min). However, it
      remains unknown whether these breaks actually represent sit-to-stand postural
      transitions in free-living. Thus, the purpose of this study was to compare free
      living accelerometer-derived and posture-derived estimates of breaks in sedentary
      time using the ActiGraph GT3X+ (AG) and the activPALTM (AP), respectively.
      METHODS: A total of 15 participants concurrently wore an AG at their waist and an
      AP on their right thigh for 7 consecutive days (24h/day - removing them only when
      in contact with water). Data from both devices were matched on minute-by-minute
      timestamps while also applying a 3-min allowance window to account for clock
      drift. Dependent t-test was used to evaluate differences in mean breaks between
      AG and AP. RESULTS: The AG detected 74+/-4.1 breaks/day (mean+/-SEM) while the AP
      detected 39+/-3.1 breaks/day (P<0.001). On average, the AG detected 67% of the AP
      breaks while 65% of the AG breaks did not correspond with AP breaks. Of the non
      corresponding AG breaks, 52% occurred when participants were sitting, 42% when
      standing, and 6% when transitioning from standing to sitting. CONCLUSION: The AG
      detected a significantly higher number of breaks in sedentary time, the majority
      of which do not correspond to sit-to-stand transitions as measured by the AP.

PMID- 25953505
TI  - Quantifying the cadence of free-living walking using event-based analysis.
AB  - PURPOSE: Free-living walking occurs over a wide range of durations and
      intensities (cadence). Therefore, its characterisation requires a full
      description of the distribution of duration and cadence of these walking events.
      The aim was to use event-based analysis to characterise this in a population with
      intermittent claudication (IC) and a healthy matched control group. METHODS:
      Seven-day walking activity was recorded using the activPAL activity monitor in a
      group of people with IC (n=30) and an age-matched control group (n=30). The
      cadence, number of steps and duration of individual walking events were
      calculated and outcomes were derived, and compared (p<0.05), based on thresholds
      applied. RESULTS: Both groups had similar number of walking events per day (392+/
      117 vs 415+/-160). The control group accumulated a greater proportion of their
      walking at higher cadences and 32% of their steps were taken at a cadence above
      100 steps/min, for the IC group this was 20%. Longer walking events had higher
      cadences and the IC group had fewer of these. As walking events became longer the
      cadence increased but the inter-event cadence variability decreased. More
      purposeful walking might occur at a higher cadence, and be performed at a
      preferred cadence. Individuals with IC had a smaller volume of walking, but these
      differences occurred almost entirely above a cadence of 90 steps/min.
      CONCLUSIONS: This is the first study which has quantified the cadence of
      continuous periods of free-living walking. The characteristics (duration, number
      of steps and cadence) of all the individual walking events were used to derive
      novel outcomes, providing new insights into free-living walking behaviour.

PMID- 25953506
TI  - The effect of shoe type and fatigue on strike index and spatiotemporal parameters
      of running.
AB  - We aimed to observe differences in running style parameters and the stride-to
      stride coefficient of variation and correlative patterns using detrended
      fluctuation analysis (DFA) between conventional and first-time minimalistic shoe
      use. We also aimed to study the effect of fatigue on these parameters. 26
      recreational runners were tested using a pressure insole device on a treadmill
      whilst wearing conventional (CONV) and minimalistic (MIN) shoes. They then
      performed a prolonged running bout simulating a fatiguing training session,
      before being tested a second time in both shoe types. Average values of strike
      index (initial ground contact point on the footsole expressed as a percentage of
      total sole length) were not significantly different between CONV [25.7+/-14.6%
      (unfatigued), 23.1+/-11.1% (fatigued)] and MIN [28.9+/-19.1% (unfatigued), 26.7+/
      17.6% (fatigued)] (p=0.501). The fatigued state also yielded a similar strike
      index compared to the unfatigued state (p=0.661). An overall trend in decreased
      inter-stride correlative patterns of strike index was observed in MIN compared to
      CONV (p=0.075). No differences in contact time, flight time, stride time, duty
      factor, stride length and stride frequency were found between shoe types. A trend
      in reduced flight time (p=0.078) and therefore increased duty factor (p=0.053)
      was observed due to fatigue. We conclude that in recreational runners, no
      meaningful, acute adaptation in running style occurs as a result of first-time
      MIN use. Similarly, runners were able to maintain their running style after a
      prolonged running bout. 

PMID- 25953509
TI  - "Less is more:" The harms of overtreatment in early ovarian cancer.

PMID- 25953508
TI  - Development and validation of a patient-reported outcome measure for stroke
      patients.
AB  - BACKGROUND: Family support and patient satisfaction with treatment are crucial
      for aiding in the recovery from stroke. However, current validated stroke
      specific questionnaires may not adequately capture the impact of these two
      variables on patients undergoing clinical trials of new drugs. Therefore, the aim
      of this study was to develop and evaluate a new stroke patient-reported outcome
      measure (Stroke-PROM) instrument for capturing more comprehensive effects of
      stroke on patients participating in clinical trials of new drugs. METHODS: A
      conceptual framework and a pool of items for the preliminary Stroke-PROM were
      generated by consulting the relevant literature and other questionnaires created
      in China and other countries, and interviewing 20 patients and 4 experts to
      ensure that all germane parameters were included. During the first item-selection
      phase, classical test theory and item response theory were applied to an initial
      scale completed by 133 patients with stroke. During the item-revaluation phase,
      classical test theory and item response theory were used again, this time with
      475 patients with stroke and 104 healthy participants. During the scale
      assessment phase, confirmatory factor analysis was applied to the final scale of
      the Stroke-PROM using the same study population as in the second item-selection
      phase. Reliability, validity, responsiveness and feasibility of the final scale
      were tested. RESULTS: The final scale of Stroke-PROM contained 46 items
      describing four domains (physiology, psychology, society and treatment). These
      four domains were subdivided into 10 subdomains. Cronbach's alpha coefficients
      for the four domains ranged from 0.861 to 0.908. Confirmatory factor analysis
      supported the validity of the final scale, and the model fit index satisfied the
      criterion. Differences in the Stroke-PROM mean scores were significant between
      patients with stroke and healthy participants in nine subdomains (P < 0.001),
      indicating that the scale showed good responsiveness. CONCLUSIONS: The Stroke
      PROM is a patient-reported outcome multidimensional questionnaire developed
      especially for clinical trials of new drugs and is focused on issues of family
      support and patient satisfaction with treatment. Extensive data analyses
      supported the validity, reliability and responsiveness of the Stroke-PROM.

PMID- 25953510
TI  - The effect of adenosine 5'-monophosphate (AMP) on tenderness, microstructure and
      chemical-physical index of duck breast meat.
AB  - BACKGROUND: Adenosine 5'-monophosphate (AMP) is often used in meat and poultry
      soups as a flavor enhancer (flavor modifier), or as food additives for specific
      nutritional purposes. Our previous research as well as evidence from others
      showed that actomyosin could be dissociated into myosin and actin by AMP in
      extracted muscle solution. However, there is no report available on the
      application of AMP to dissociate actomyosin and to improve meat tenderness. The
      objectives of this study were to evaluate the effect of AMP on duck meat
      tenderness and other quality traits and to explore the mechanism of the action of
      AMP on meat tenderness. RESULTS: Duck breast muscle was treated with 0, 10, 20,
      30, 40 mmol L(-1) AMP at 5  degrees C for 10 h and examined for shear force,
      microstructure, actomyosin dissociation, myofibril fragmentation index (MFI), pH,
      water content, cooking loss, CIE* color (L*, a*, b*), inosine monophosphate (IMP)
      and free amino acid (FAA) contents. Results showed that shear force, cooking
      loss, L* and b* of the muscles significantly decreased after AMP treatment (P <
      0.05); actomyosin dissociation, MFI, pH, water content, fiber diameter, sarcomere
      length, IMP and ammonia significantly increased (P < 0.05); no significant change
      in a* or other FAA content was observed (P > 0.05), and muscle shrinkage in
      transverse and longitudinal directions were restrained after AMP treatment.
      CONCLUSION: The results suggest that AMP could notably improve meat tenderness,
      and this effect was probably mainly through increasing muscle pH, promoting
      actomyosin dissociation and disrupting the Z-line; meanwhile, the conversion of
      AMP to IMP may contribute to the flavor of meat.

PMID- 25953512
TI  - Discovery of (1R,2S)-2-{[(2,4-Dimethylpyrimidin-5-yl)oxy]methyl}-2-(3
      fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide (E2006): A Potent
      and Efficacious Oral Orexin Receptor Antagonist.
AB  - The orexin/hypocretin receptors are a family of G protein-coupled receptors and
      consist of orexin-1 (OX1) and orexin-2 (OX2) receptor subtypes. Orexin receptors
      are expressed throughout the central nervous system and are involved in the
      regulation of the sleep/wake cycle. Because modulation of these receptors
      constitutes a promising target for novel treatments of disorders associated with
      the control of sleep and wakefulness, such as insomnia, the development of orexin
      receptor antagonists has emerged as an important focus in drug discovery
      research. Here, we report the design, synthesis, characterization, and structure
      activity relationships (SARs) of novel orexin receptor antagonists. Various
      modifications made to the core structure of a previously developed compound (-)
      5, the lead molecule, resulted in compounds with improved chemical and
      pharmacological profiles. The investigation afforded a potential therapeutic
      agent, (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)-N
      (5-fluoropyridin-2-yl)cyclopropanecarboxamide (E2006), an orally active, potent
      orexin antagonist. The efficacy was demonstrated in mice in an in vivo study by
      using sleep parameter measurements. 

PMID- 25953511
TI  - Soy glyceollins regulate transcript abundance in the female mouse brain.
AB  - Glyceollins (Glys), produced by soy plants in response to stress, have anti
      estrogenic activity in breast and ovarian cancer cell lines in vitro and in vivo.
      In addition to known anti-estrogenic effects, Gly exhibits mechanisms of action
      not involving estrogen receptor (ER) signaling. To date, effects of Gly on gene
      expression in the brain are unknown. For this study, we implanted 17-beta
      estradiol (E2) or placebo slow-release pellets into ovariectomized CFW mice
      followed by 11 days of exposure to Gly or vehicle i.p. injections. We then
      performed a microarray on total RNA extracted from whole-brain hemispheres and
      identified differentially expressed genes (DEGs) by a 2 * 2 factorial ANOVA with
      an false discovery rate (FDR) = 0.20. In total, we identified 33 DEGs with a
      significant E2 main effect, 5 DEGs with a significant Gly main effect, 74 DEGs
      with significant Gly and E2 main effects (but no significant interaction term),
      and 167 DEGs with significant interaction terms. Clustering across all DEGs
      revealed that transcript abundances were similar between the E2 + Gly and E2-only
      treatments. However, gene expression after Gly-only treatment was distinct from
      both of these treatments and was generally characterized by higher transcript
      abundance. Collectively, our results suggest that whether Gly acts in the brain
      through ER-dependent or ER-independent mechanisms depends on the target gene.

PMID- 25953513
TI  - Chryseobacterium indologenes in four patients with leukemia.
AB  - Chryseobacterium indologenes is a rare opportunistic pathogen causing hospital
      acquired infection. We present 4 patients with leukemia associated with C.
      indologenes infection. Two of the patients, undergoing peripheral blood
      allogeneic hematopoietic stem cell transplantation (alloHSCT) from human
      leukocyte antigen-identical sibling donors, died of pneumonia caused by C.
      indologenes with or without Pseudomonas aeruginosa. Blood infection with C.
      indologenes was found in the other 2 patients during chemotherapy, 1 of which was
      a central venous catheter-related bloodstream infection. Both patients were cured
      with or without the sensitive antibiotic. Three of these 4 isolates were
      susceptible to trimethoprim-sulfamethoxazole only in vitro. Although C.
      indologenes has a weak toxicity, it can be lethal for the super-immunocompromised
      patients, such as those treated with alloHSCT.

PMID- 25953507
TI  - Exploiting replicative stress to treat cancer.
AB  - DNA replication in cancer cells is accompanied by stalling and collapse of the
      replication fork and signalling in response to DNA damage and/or premature
      mitosis; these processes are collectively known as 'replicative stress'. Progress
      is being made to increase our understanding of the mechanisms that govern
      replicative stress, thus providing ample opportunities to enhance replicative
      stress for therapeutic purposes. Rather than trying to halt cell cycle
      progression, cancer therapeutics could aim to increase replicative stress by
      further loosening the checkpoints that remain available to cancer cells and
      ultimately inducing the catastrophic failure of proliferative machineries. In
      this Review, we outline current and future approaches to achieve this,
      emphasizing the combination of conventional chemotherapy with targeted
      approaches. 

PMID- 25953515
TI  - Partitioned EDGE devices for high throughput production of monodisperse emulsion
      droplets with two distinct sizes.
AB  - We present a novel microfluidic EDGE (Edge based Droplet GEneration) device with
      regularly spaced micron-sized partitions, which is aimed at upscaling of o/w
      emulsion preparation. By this means, remarkably higher pressure stability was
      obtained, and two orders of magnitude higher droplet formation frequency was
      achieved compared to regular EDGE devices. Interestingly, we observed two
      different monodisperse droplet formation regimes for plateaus that were 2
      micrometres in height, and to the best of our knowledge, no other microfluidic
      device has this ability. The average diameters of the droplets were 9 and 28 MUm,
      both with a coefficient of variation (CV) below 5%. Based on the experimental
      throughput and a plausible mass parallelization scenario, the amount of
      hexadecane that can be emulsified is estimated to be between 6 and 25 m(3) m(-2)
      h(-1) depending on the required droplet size. With its high throughput potential
      and ability to produce uniform droplets of two different sizes, the partitioned
      EDGE device is promising for industrial emulsion production. 

PMID- 25953514
TI  - The collagen I mimetic peptide DGEA enhances an osteogenic phenotype in
      mesenchymal stem cells when presented from cell-encapsulating hydrogels.
AB  - Interactions between cells and the extracellular matrix (ECM) are known to play
      critical roles in regulating cell phenotype. The identity of ECM ligands
      presented to mesenchymal stem cells (MSCs) has previously been shown to direct
      the cell fate commitment of these cells. To enhance osteogenic differentiation of
      MSCs, alginate hydrogels were prepared that present the DGEA ligand derived from
      collagen I. When presented from hydrogel surfaces in 2D, the DGEA ligand did not
      facilitate cell adhesion, while hydrogels presenting the RGD ligand derived from
      fibronectin did encourage cell adhesion and spreading. However, the osteogenic
      differentiation of MSCs encapsulated within alginate hydrogels presenting the
      DGEA ligand was enhanced when compared with unmodified alginate hydrogels and
      hydrogels presenting the RGD ligand. MSCs cultured in DGEA-presenting gels
      exhibited increased levels of osteocalcin production and mineral deposition.
      These data suggest that the presentation of the collagen I-derived DGEA ligand is
      a feasible approach for selectively inducing an osteogenic phenotype in
      encapsulated MSCs.

PMID- 25953516
TI  - Reinforcement of injectable calcium phosphate cement by gelatinized starches.
AB  - Current injectable calcium phosphate bone cements (CPC) encounter the problems of
      low strength, high brittleness, and low cohesion in aqueous environment, which
      greatly hinder their clinical applications for loading-bearing bone substitution
      and minimally invasive orthopedic surgeries. Here, a strategy of using
      gelatinized starches to reinforce injectable CPC was investigated. Four types of
      starches, namely corn starch, crosslinked starch, cationic starch, and Ca
      modified starch, were studied for their influence on CPC mechanical properties,
      injectability, setting times, anticollapsibility, and cytocompatibility.
      Gelatinized starch significantly improved compressive strength and modulus as
      well as strain energy density of CPC to different extents. Specifically, both
      corn starch and Ca-modified starch revealed sixfold and more than twofold
      increases in the compressive strength and modulus of CPC, respectively. The
      addition of gelatinized starches with proper contents increased the injectability
      and anticollapsibility of CPC. In addition, osteoblast proliferation tests on
      leaching solution of modified cements showed that gelatinized starches had no
      adverse effect on cell proliferation, and all cement samples resulted in better
      osteoblast proliferation compared to phosphate-buffered solution control. The
      mechanisms behind the reinforcing effect of different starches were preliminarily
      studied. Two possible mechanisms, reinforcement by the second phase of
      gelatinized starch and strong interlocking of apatite crystals, were proposed
      based on the results of starch zeta potential and viscosity, cement
      microstructure, and resultant mechanical properties. In conclusion, incorporating
      gelatinized starches could be an effective, facile, and bio-friendly strategy to
      reinforce injectable CPC and improve its mechanical stability, and thus, should
      be further studied and developed.

PMID- 25953517
TI  - Breast cancer heterogeneity: parallel evolution or conscious uncoupling?
AB  - Breast cancer is known to display considerable inter- and intra-tumour genetic
      heterogeneity. It is now widely accepted that no two breast cancers harbour the
      same complement of genomic alterations, and that both primary and metastatic
      breast cancers are composed of multiple genetically diverse subclones that evolve
      under different selective pressures. Recent work published in the Journal of
      Pathology by Desmedt and colleagues questions the evolutionary dynamics of multi
      focal breast cancer with similar pathological features by studying the mutational
      repertoire of different lesions. Whilst the majority of the lesions showed some
      common driver alterations, one-third lacked any common mutations, suggesting very
      early clonal divergence. These and other recent observations underscore the need
      for a fundamental understanding of the rules governing breast cancer evolution,
      and highlight the need for in-depth assessment of driver alterations for
      appropriate patient management and selective treatment.

PMID- 25953518
TI  - Overexpression of HSP47 in esophageal squamous cell carcinoma: clinical
      implications and functional analysis.
AB  - Several biomarkers of esophageal squamous cell carcinoma (ESCC) have been
      explored to improve the prognosis of this disease. One of these, the 47-kDa heat
      shock protein (HSP47), has been screened as a potential biomarker by genomic
      profiling and is known to be overexpressed in some malignant diseases. In this
      study, we explored the role and evaluated the prognostic value of HSP47
      expression in ESCC. The function of this protein was analyzed by assaying
      proliferation, wound healing, and colony formation in an HSP47-knockdown ESCC
      line. The prognostic implication of HSP47 expression was analyzed by
      immunohistochemical staining in 157 surgical specimens. HSP47 expression level
      and other clinical variables were analyzed using multivariate Cox proportional
      hazards models. Silencing of the HSP47 gene in the ESCC cell line inhibited cell
      proliferation and colony formation. HSP47 was highly expressed in ESCC tissue
      samples, compared with normal esophageal tissues. The level of
      immunohistochemical staining of HSP47 and pathologic stage were significantly
      correlated with overall and recurrence-free survival, as shown by multivariate
      analysis (P = 0.014 and 0.044, respectively). We found that overexpression of
      HSP47 is associated with poor prognosis in patients with ESCC and that this is
      consistent with the function of HSP47 in terms of increased cell proliferation
      and colony formation. These results suggest that HSP47 is a potential prognostic
      biomarker for ESCC and merits further research for novel diagnostic and
      therapeutic applications.

PMID- 25953519
TI  - Unusual imaging findings in a patient with AL amyloidosis.

PMID- 25953520
TI  - Must "second victims" always be in the wrong?

PMID- 25953522
TI  - The Effect of Oxidation on Berberine-Mediated CYP1 Inhibition: Oxidation Behavior
      and Metabolite-Mediated Inhibition.
AB  - The protoberberine alkaloid berberine carries methylenedioxy moiety and exerts a
      variety of pharmacological effects, such as anti-inflammation and lipid-lowering
      effects. Berberine causes potent CYP1B1 inhibition, whereas CYP1A2 shows
      resistance to the inhibition. To reveal the influence of oxidative metabolism on
      CYP1 inhibition by berberine, berberine oxidation and the metabolite-mediated
      inhibition were determined. After NADPH-fortified preincubation of berberine with
      P450, the inhibition of CYP1A1 and CYP1B1 variants (CYP1B1.1, CYP1B1.3, and
      CYP1B1.4) by berberine was not enhanced, and CYP1A2 remained resistant.
      Demethyleneberberine was identified as the most abundant metabolite of CYP1A1-
      and CYP1B1-catalyzed oxidations, and thalifendine was generated at a relatively
      low rate. CYP1A1-catalyzed berberine oxidation had the highest maximal velocity
      (V max) and exhibited positive cooperativity, suggesting the assistance of
      substrate binding when the first substrate was present. In contrast, the
      demethylenation by CYP1B1 showed the property of substrate inhibition. CYP1B1
      catalyzed berberine oxidation had low K m values, but it had V max values less
      than 8% of those of CYP1A1. The dissociation constants generated from the binding
      spectrum and fluorescence quenching suggested that the low K m values of CYP1B1
      catalyzed oxidation might include more than the rate constants describing
      berberine binding. The natural protoberberine/berberine fmetabolites with
      methylenedioxy ring-opening (palmatine, jatrorrhizine, and demethyleneberberine)
      and the demethylation (thalifendine and berberrubine) caused weak CYP1
      inhibition. These results demonstrated that berberine was not efficiently
      oxidized by CYP1B1, and metabolism-dependent irreversible inactivation was
      minimal. Metabolites of berberine caused a relatively weak inhibition of CYP1. 

PMID- 25953523
TI  - Alcohol, Isolation, and Access to Treatment: Family Physician Experiences of
      Alcohol Consumption and Access to Health Care in Rural British Columbia.
AB  - OBJECTIVE: The purpose of this project was to study the experiences of physicians
      who treat persons with alcohol-attributed diseases in rural areas of British
      Columbia, Canada. METHOD: A cross-sectional survey was distributed to primary
      health care physicians that had a family practice in a designated rural community
      using the Rural Coordination Centre of British Columbia's community isolation
      rating system. Data were collected through a mail and online survey sent to
      primary health care physicians. Purposeful sampling was used to select
      participants that had a primary health care practice in a designated rural
      community. RESULTS: Surveys were returned by 22% of potential participants (N =
      67) that had an average of 15.8 years in family practice. The majority of
      participants (95.4%) reported that alcohol had a negative impact on population
      health, and physicians expressed particular concern for alcohol consumption in
      relation to mental health (85.1%) and physical illness (82.1%). Most participants
      had referred patients out of the community for treatment; however, 76.4% reported
      difficulty with referrals, including long wait-lists, limited services, and
      issues related to transportation and leaving the community for substance use
      treatment. CONCLUSION: Rural physicians showed an awareness and concern for
      alcohol consumption in their community, but they also reported difficulties
      referring patients for substance use treatment. Additional study is required to
      understand how to improve the continuity of care provided to persons with alcohol
      related issues in rural British Columbia.

PMID- 25953521
TI  - Expression of UDP-Glucuronosyltransferase 1 (UGT1) and Glucuronidation Activity
      toward Endogenous Substances in Humanized UGT1 Mouse Brain.
AB  - Although UDP-glucuronosyltransferases (UGTs) are important phase II drug
      metabolizing enzymes, they are also involved in the metabolism of endogenous
      compounds. Certain substrates of UGTs, such as serotonin and estradiol, play
      important roles in the brain. However, the expression of UGTs in the human brain
      has not been fully clarified. Recently, humanized UGT1 mice (hUGT1 mice) in which
      the original Ugt1 locus was disrupted and replaced with the human UGT1 locus have
      been developed. In the present study, the expression pattern of UGT1As in brains
      from humans and hUGT1 mice was examined. We found that UGT1A1, 1A3, 1A6, and 1A10
      were expressed in human brains. The expression pattern of UGT1As in hUGT1 mouse
      brains was similar to that in human brains. In addition, we examined the
      expression of UGT1A1 and 1A6 in the cerebellum, olfactory bulbs, midbrain,
      hippocampus, and cerebral cortex of hUGT1 mice. UGT1A1 in all brain regions and
      UGT1A6 in the cerebellum and cerebral cortex of 6-month-old hUGT1 mice were
      expressed at a significantly higher rate than those of 2-week-old hUGT1 mice. A
      difference in expression levels between brain regions was also observed. Brain
      microsomes exhibited glucuronidation activities toward estradiol and serotonin,
      with mean values of 0.13 and 5.17 pmol/min/mg, respectively. In conclusion,
      UGT1A1 and UGT1A6 might play an important role in function regulation of
      endogenous compounds in a region- and age-dependent manner. Humanized UGT1 mice
      might be useful to study the importance of brain UGTs in vivo. 

PMID- 25953525
TI  - Gastrointestinal stenting: Current status and imaging features.
AB  - The use of stents in the gastrointestinal tract has been subjected to major
      changes. Initially, the use of stents was restricted to malignant strictures in
      patients with metastatic disease. But thanks to reduction of the morbidity and
      mortality rates, they are now used with curative intention and in patients with
      benign diseases after careful selection. However, for patients presenting with
      colon obstruction due to an advanced colon carcinoma, the mortality and morbidity
      are still high. The purpose of this review is to provide an overview of
      indications, techniques and further developments of the stents in the
      gastrointestinal tract and to highlight the predominant role of multidetector row
      computed tomography (MDCT) in the detection of potential complications. 

PMID- 25953524
TI  - Decreased orexin (hypocretin) immunoreactivity in the hypothalamus and pontine
      nuclei in sudden infant death syndrome.
AB  - Infants at risk of sudden infant death syndrome (SIDS) have been shown to have
      dysfunctional sleep and poor arousal thresholds. In animal studies, both these
      attributes have been linked to impaired signalling of the neuropeptide orexin.
      This study examined the immunoreactivity of orexin (OxA and OxB) in the tuberal
      hypothalamus (n = 27) and the pons (n = 15) of infants (1-10 months) who died
      from SIDS compared to age-matched non-SIDS infants. The percentage of orexin
      immunoreactive neurons and the total number of neurons were quantified in the
      dorsomedial, perifornical and lateral hypothalamus at three levels of the tuberal
      hypothalamus. In the pons, the area of orexin immunoreactive fibres were
      quantified in the locus coeruleus (LC), dorsal raphe (DR), laterodorsal tegmental
      (LDT), medial parabrachial, dorsal tegmental (DTg) and pontine nuclei (Pn) using
      automated methods. OxA and OxB were co-expressed in all hypothalamic and pontine
      nuclei examined. In SIDS infants, orexin immunoreactivity was decreased by up to
      21 % within each of the three levels of the hypothalamus compared to non-SIDS (p
      <= 0.050). In the pons, a 40-50 % decrease in OxA occurred in the all pontine
      nuclei, while a similar decrease in OxB immunoreactivity was observed in the LC,
      LDT, DTg and Pn (p <= 0.025). No correlations were found between the decreased
      orexin immunoreactivity and previously identified risk factors for SIDS,
      including prone sleeping position and cigarette smoke exposure. This finding of
      reduced orexin immunoreactivity in SIDS infants may be associated with sleep
      dysfunction and impaired arousal.

PMID- 25953526
TI  - Single-stage posterior vertebral column resection and internal fixation for old
      fracture-dislocations of thoracolumbar spine: a case series and systematic
      review.
AB  - PURPOSE: To evaluate the efficacy of single-stage posterior vertebral column
      resection for old thoracolumbar fracture-dislocations with spinal cord injury.
      METHODS: From January 2007 to June 2013, twelve male patients (average age, 32.6
      years; range 19-57 years) with old fracture-dislocations of the thoracolumbar
      spine and spinal cord injury underwent single-stage posterior vertebral column
      resection and internal fixation. All patients were assessed for relief of the
      pain and restoration of neurologic function. Postoperative Cobb angle was
      measured and bone graft fusion was evaluated by X-ray. A systematic review of 25
      studies evaluating surgical management of thoracolumbar fractures with spinal
      cord injuries was also performed. RESULTS: From our case series, six of the nine
      patients with Frankel grade A had significant improvement in urination and
      defecation after surgery. The three patients with Frankel grades B and C had
      progression of 1-2 grades after surgery. Bony fusion was achieved and local back
      pain was relieved in all patients after surgery. From our systematic review of 25
      studies, the majority of patients had improved back pain, the postoperative
      kyphotic angle was significantly reduced compared with pre-operative kyphotic
      angle. CONCLUSION: Single-stage posterior vertebral column resection and internal
      fixation for old thoracolumbar fracture-dislocations is an ideal treatment
      allowing for thorough decompression, relief of pain, correction of deformities,
      and restoration of spinal stability. LEVEL OF EVIDENCE: IV.

PMID- 25953528
TI  - Erratum to: Core outcome domains for clinical trials in non-specific low back
      pain.

PMID- 25953527
TI  - The surgical algorithm for the AOSpine thoracolumbar spine injury classification
      system.
AB  - PURPOSE: The goal of the current study is to establish a surgical algorithm to
      accompany the AOSpine thoracolumbar spine injury classification system. METHODS:
      A survey was sent to AOSpine members from the six AO regions of the world, and
      surgeons were asked if a patient should undergo an initial trial of conservative
      management or if surgical management was warranted. The survey consisted of
      controversial injury patterns. Using the results of the survey, a surgical
      algorithm was developed. RESULTS: The AOSpine Trauma Knowledge forum defined that
      the injuries in which less than 30% of surgeons would recommend surgical
      intervention should undergo a trial of non-operative care, and injuries in which
      70% of surgeons would recommend surgery should undergo surgical intervention.
      Using these thresholds, it was determined that injuries with a thoracolumbar
      AOSpine injury score (TL AOSIS) of three or less should undergo a trial of
      conservative treatment, and injuries with a TL AOSIS of more than five should
      undergo surgical intervention. Operative or non-operative treatment is acceptable
      for injuries with a TL AOSIS of four or five. CONCLUSION: The current algorithm
      uses a meaningful injury classification and worldwide surgeon input to determine
      the initial treatment recommendation for thoracolumbar injuries. This allows for
      a globally accepted surgical algorithm for the treatment of thoracolumbar trauma.

PMID- 25953529
TI  - Innervated Digital Artery Perforator Propeller Flap for Reconstruction of Lateral
      Oblique Fingertip Defects.
AB  - PURPOSE: To report our experience with the use of a digital artery perforator
      propeller flap based on a constant distal perforator in the middle phalanx for
      resurfacing of lateral oblique fingertip amputations. METHODS: Twelve fingertips
      in 10 patients underwent reconstruction, with a mean follow-up of 8 months
      (range, 8-12 mo). The size of the flaps ranged from 2.5 * 1.5 cm to 3.0 * 2.0 cm.
      RESULTS: All flaps survived entirely and restored a rounded fingertip contour.
      Mean static 2-point discrimination was 5 mm (range, 4-6 mm). With the exception
      of 1 patient with an amputation at the distal interphalangeal joint, the distal
      interphalangeal joint was preserved in all patients and had 30 degrees  to 60
      degrees  of motion at final follow-up. No patients complained of cold intolerance
      or residual joint contracture. No hooked nail deformity occurred in patients who
      had remaining nailbed. CONCLUSIONS: The digital artery perforator propeller flap
      is particularly suited to coverage of a lateral oblique fingertip defect, because
      only a 90 degrees  rotation is required when inset, and the bulk of the flap
      serves to restore the rounded contour of the fingertip. The skin over the entire
      dorsal surface of the middle phalanx can be elevated as a flap, providing
      adequate tissue to resurface the defect and restore a rounded contour to the
      fingertip. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 25953530
TI  - CD 30-positive transformed follicular lymphoma: two case reports and literature
      review.
AB  - AIMS: Here we report two cases of follicular lymphoma that transformed to CD30
      positive diffuse large B cell lymphoma and review the literature on this topic.
      RESULTS: The first case represents an example of early transformation of
      conventional low-grade follicular lymphoma to CD30-positive large B cell
      lymphoma. Immunoglobulin (Ig)H and cytogenetic identity was demonstrated between
      both components. High-dose and auto-stem cell transplant (SCT) was applied and
      complete response was achieved. The second case represents an example of d'emblee
      transformation of intrafollicular neoplasia to CD30-positive large B cell
      lymphoma. Immunoglobulin K deleting element (IgKde) and cytogenetic identity
      between both phases was demonstrated. The patient was in partial response after
      four cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine and
      prednisone (R-CHOP). CONCLUSIONS: CD30 expression was found to be associated in
      these cases to the transformation event and could be considered a therapeutic
      target to add to conventional immunochemotherapeutic regimens, even in
      combination with auto-SCT. We suggest looking for CD30 expression in transformed
      follicular lymphoma cases.

PMID- 25953532
TI  - Warning about the harms of tobacco use in 22 countries: findings from a cross
      sectional household survey.
AB  - BACKGROUND: Knowledge about the harms of tobacco use deters initiation and is
      associated with cessation. Most studies on this knowledge in the general
      population have been in high-income countries, but the tobacco use burden is
      increasing in low-income and middle-income countries. We sought to estimate
      levels of knowledge about tobacco-related diseases in 22 countries and determine
      the factors associated with differences in knowledge. METHODS: We used data from
      the Global Adult Tobacco Survey (GATS), a nationally representative survey of
      persons aged >=15 years. GATSs were conducted from 2008 to 2013 in 22 low-income
      and middle-income countries. Information was gathered on tobacco-related
      knowledge and noticing of antismoking mass media messages and health warning
      labels on cigarette packages. We constructed a four-point knowledge scale and
      performed multivariate regression analyses. RESULTS: Median country values for
      the proportion of adults who believed smoking causes a specific illness were
      95.9% for lung cancer, 82.5% for heart attack and 74.0% for stroke. Knowledge
      scores ranged from 2.1 to 3.8. In multivariate regressions, adults scored
      significantly higher on the knowledge scale if they noticed antismoking media
      messages (22 countries) or health warning labels (17 countries). Significantly
      higher knowledge scores occurred in all 9 countries with pictorial health warning
      labels compared with only 8 out of 13 countries with text-only warning labels.
      CONCLUSIONS: Antismoking media messages appear effective for warning the public
      about the harms from tobacco use in all 22 countries, while warning labels are
      effective in the majority of these countries. Our findings suggest opportunities
      to motivate smoking cessation globally.

PMID- 25953531
TI  - Perioperative cardiovascular monitoring of high-risk patients: a consensus of 12.
AB  - A significant number of surgical patients are at risk of intra- or post-operative
      complications or both, which are associated with increased lengths of stay,
      costs, and mortality. Reducing these risks is important for the individual
      patient but also for health-care planners and managers. Insufficient tissue
      perfusion and cellular oxygenation due to hypovolemia, heart dysfunction or both
      is one of the leading causes of perioperative complications. Adequate
      perioperative management guided by effective and timely hemodynamic monitoring
      can help reduce the risk of complications and thus potentially improve outcomes.
      In this review, we describe the various available hemodynamic monitoring systems
      and how they can best be used to guide cardiovascular and fluid management in the
      perioperative period in high-risk surgical patients. 

PMID- 25953533
TI  - Surface chemical and biological characterization of flax fabrics modified with
      silver nanoparticles for biomedical applications.
AB  - Silver nanophases are increasingly used as effective antibacterial agent for
      biomedical applications and wound healing. This work aims to investigate the
      surface chemical composition and biological properties of silver nanoparticle
      modified flax substrates. Silver coatings were deposited on textiles through the
      in situ photo-reduction of a silver solution, by means of a large-scale
      apparatus. The silver-coated materials were characterized through X-ray
      Photoelectron Spectroscopy (XPS), to assess the surface elemental composition of
      the coatings, and the chemical speciation of both the substrate and the
      antibacterial nanophases. A detailed investigation of XPS high resolution regions
      outlined that silver is mainly present on nanophases' surface as Ag2O. Scanning
      electron microscopy and energy dispersive X-ray spectroscopy were also carried
      out, in order to visualize the distribution of silver particles on the fibers.
      The materials were also characterized from a biological point of view in terms of
      antibacterial capability and cytotoxicity. Agar diffusion tests and bacterial
      enumeration tests were performed on Gram positive and Gram negative bacteria,
      namely Staphylococcus aureus and Escherichia coli. In vitro cytotoxicity tests
      were performed through the extract method on murine fibroblasts in order to
      verify if the presence of the silver coating affected the cellular viability and
      proliferation. Durability of the coating was also assessed, thus confirming the
      successful scaling up of the process, which will be therefore available for large
      scale production. 

PMID- 25953534
TI  - Magnesium substitution in the structure of orthopedic nanoparticles: A comparison
      between amorphous magnesium phosphates, calcium magnesium phosphates, and
      hydroxyapatites.
AB  - As biocompatible materials, magnesium phosphates have received a lot of attention
      for orthopedic applications. During the last decade multiple studies have shown
      advantages for magnesium phosphate such as lack of cytotoxicity,
      biocompatibility, strong mechanical properties, and high biodegradability. The
      present study investigates the role of Mg(+2) and Ca(+2) ions in the structure of
      magnesium phosphate and calcium phosphate nanoparticles. To directly compare the
      effect of Mg(+2) and Ca(+2) ions on structure of nanoparticles and their
      biological behavior, three groups of nanoparticles including amorphous magnesium
      phosphates (AMPs) which release Mg(+2), calcium magnesium phosphates (CMPs) which
      release Mg(+2) and Ca(+2), and hydroxyapatites (HAs) which release Ca(+2) were
      studied. SEM, TEM, XRD, and FTIR were used to evaluate the morphology,
      crystallinity, and chemical properties of the particles. AMP particles were
      homogeneous nanospheres, whereas CMPs were combinations of heterogeneous nanorods
      and nanospheres, and HAs which contained heterogeneous nanosphere particles. Cell
      compatibility was monitored in all groups to determine the cytotoxicity effect of
      particles on studied MC3T3-E1 preosteoblasts. AMPs showed significantly higher
      attachment rate than the HAs after 1 day and both AMPs and CMPs showed
      significantly higher proliferation rate when compared to HAs after 7days. Gene
      expression level of osteoblastic markers ALP, COL I, OCN, OPN, RUNX2 were
      monitored and they were normalized to GAPDH housekeeping gene. Beta actin
      expression level was monitored as the second housekeeping gene to confirm the
      accuracy of results. In general, AMPs and CMPs showed higher expression level of
      osteoblastic genes after 7 days which can further confirm the stimulating role of
      Mg(+2) and Ca(+2) ions in increasing the proliferation rate, differentiation, and
      mineralization of MC3T3-E1 preosteoblasts.

PMID- 25953536
TI  - Synthesis and characterization of biodegradable polyurethane films based on HDI
      with hydrolyzable crosslinked bonds and a homogeneous structure for biomedical
      applications.
AB  - Synthetic biodegradable polymers are considered strategic in the biomaterials
      field and are used in various applications. Among the polymers used as
      biomaterials, polyurethanes (PUs) feature prominently due to their versatility
      and the ability to obtain products with a wide range of physical and mechanical
      properties. In this work, new biodegradable polyurethane films were developed
      based on hexamethylene diisocyanate (HDI) and glycerol as the hard segment (HS),
      and poly(caprolactone) triol (PCL triol) and low-molecular-weight poly(ethylene
      glycol) PEG as the soft segment (SS) without the use of a catalyst. The films
      obtained were characterized by structural, mechanical and biological testing. A
      highly connected network with a homogeneous PU structure was obtained due to
      crosslinked bonds. The films showed amorphous structures, high water uptake,
      hydrogel behavior, and susceptibility to hydrolytic degradation. Mechanical tests
      indicated that the films reached a high deformation at break of up to 425.4%, an
      elastic modulus of 1.6 MPa and a tensile strength of 3.6 MPa. The materials
      presented a moderate toxic effect on MTT assay and can be considered potential
      materials for biomedical applications.

PMID- 25953535
TI  - A humidity sensitive two-dimensional tunable amorphous photonic structure in the
      outer layer of bivalve ligament from Sunset Siliqua.
AB  - A humidity sensitive two-dimensional tunable amorphous photonic structure (2D
      TAPS) in the outer layer of bivalve ligament from Sunset Siliqua (OLLS) was
      reported in this paper. The structural color and microstructure of OLLS were
      investigated by reflection spectra and scanning electron microscopy,
      respectively. The results indicate that the reflection peak wavelength of the wet
      OLLS blue-shifts from 454 nm to 392 nm with the increasing of air drying time
      from 0 to 40 min, while the reflectivity decreases gradually and vanishes at
      last, relevant color changes from blue to black background color. The structural
      color in the OLLS is produced by a two-dimensional amorphous photonic structure
      consisting of aligned protein fibers, in which the diameter of protein fiber and
      the inter-fiber spacing are 101 +/- 12 nm. Water can reversibly tune the
      reflection peak wavelength and reflectivity of this photonic structure, and the
      regulation achieved through dynamically tuning the interaction between inter
      fiber spacing and average refractive index.

PMID- 25953538
TI  - Blood compatibility of a ferulic acid (FA)-eluting PHBHHx system for
      biodegradable magnesium stent application.
AB  - Magnesium stent has shown potential application as a new biodegradable stent.
      However, the fast degradation of magnesium stent limited its clinic application.
      Recently, a biodegradable and drug-eluting coating system was designed to prevent
      magnesium from fast degradation by adding ferulic acid (FA) in poly (3
      hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) by a physical method. In vitro
      study has demonstrated that the FA-eluting system exhibited strong promotion to
      the endothelialization, which might be a choice for the stent application. In
      this paper, the hemolysis rate, the plasma recalcification time (PRT), the plasma
      prothrombin time (PT) and the kinetic clotting time of the FA-eluting films were
      investigated and the platelet adhesion was observed in order to assess the blood
      compatibility of the FA-eluting PHBHHx films in comparison with PHBHHx film. The
      results have shown that the addition of FA had no influence on the hemolysis, but
      prolonged PRT, PT and the clotting time and reduced the platelet adhesion and
      activation, displaying that the FA-eluting PHBHHx exhibited better blood
      compatibility than PHBHHx. In addition, the effect of alkali treatment on the
      blood compatibility of FA-eluting PHBHHx was also studied. It was indicated that
      alkali treatment had no effect on the hemolysis and the coagulation time, but
      enhanced slightly the platelet adhesion. All these demonstrated that FA-eluting
      PHBHHx film had good blood compatibility and might be a candidate surface coating
      for the biodegradable magnesium stent. 

PMID- 25953537
TI  - The fungicidal properties of the carbon materials obtained from chitin and
      chitosan promoted by copper salts.
AB  - Renewable raw materials chitin and chitosan (N-deacetylated derivative of chitin)
      were subjected to action of different copper modifiers that were carbonized in
      the atmosphere of the N2 inert gas. As a result of the novel manufacturing
      procedure, a series of carbon materials was obtained with developed surface area
      and containing copper derivatives of differentiated form, size, and dispersion.
      The copper modifier and manufacturing procedure (concentration, carbonization
      temperature) influence the physical-chemical and fungicide properties of the
      carbons. The received carbons were chemically characterized using several methods
      like low-temperature adsorption of nitrogen, X-ray diffraction analysis, scanning
      electron microscopy, cyclic voltammetry, elemental analysis, and bioassay.
      Besides chemical testing, some biological tests were performed and let to select
      carbons with the highest fungicidal activity. Such carbons were characteristic of
      the specific form of copper derivatives occurring in them, i.e., nanocrystallites
      of Cu(0) and/or Cu2O of high dispersion on the surface of carbon. The carbons may
      find an application as effective contact fungistatic agents in cosmetology,
      medicine, food industry, etc. 

PMID- 25953539
TI  - Osteoblastic differentiation of stem cells from human exfoliated deciduous teeth
      induced by thermosensitive hydrogels with strontium phosphate.
AB  - Stem cells from human exfoliated deciduous teeth (SHEDs) are a novel source of
      multi-potential stem cells for tissue engineering because of their potential to
      differentiate into multiple cell lineages. Strontium exhibits an important
      function in bone remodeling because it can simulate bone formation and decrease
      bone resorption. Hydrogels can mimic the natural cellular environment. The
      association of hydrogels with cell viability is determined using biological
      tests, including rheological experiments. In this study, osteogenic
      differentiation was investigated through SHED encapsulation in hydrogels
      containing strontium phosphate. Results of 3-(4, 5-dimethylthiazol-2-yl)-2, 5
      diphenyltetrazolium bromide (MTT) and proliferating cell nuclear antigen (PCNA)
      immunofluorescence staining indicated that the cells grew well and SHEDs
      proliferated in the hydrogels. Strontium-loaded chitosan-based hydrogels induced
      the biomineralization and high expression of alkaline phosphatase. Moreover, the
      expression levels of bone-related genes, including type-I collagen, Runx2,
      osteopontin (OP), and osteonectin (ON), were up-regulated during the osteogenic
      differentiation of SHEDs. This study demonstrated that strontium can be an
      effective inducer of osteogenesis for SHEDs. Elucidating the function of
      bioceramics (such as strontium) is useful in designing and developing strategies
      for bone tissue engineering. 

PMID- 25953540
TI  - Elastic properties of a porous titanium-bone tissue composite.
AB  - The porous titanium implants were introduced into the condyles of tibias and
      femurs of sheep. New bone tissue fills the pore, and the porous titanium-new bone
      tissue composite is formed. The duration of composite formation was 4, 8, 24 and
      52 weeks. The formed composites were extracted from the bone and subjected to a
      compression test. The Young's modulus was calculated using the measured stress
      strain curve. The time dependence of the Young's modulus of the composite was
      obtained. After 4 weeks the new bone tissue that filled the pores does not affect
      the elastic properties of implants. After 24 and 52 weeks the Young's modulus
      increases by 21-34% and 62-136%, respectively. The numerical calculations of the
      elasticity of porous titanium-new bone tissue composite were conducted using a
      simple polydisperse model that is based on the consideration of heterogeneous
      structure as a continuous medium with spherical inclusions of different sizes.
      The kinetics of the change in the elasticity of the new bone tissue is presented
      via the intermediate characteristics, namely the relative ultimate tensile
      strength or proportion of mature bone tissue in the bone tissue. The calculated
      and experimentally measured values of the Young's modulus of the composite are in
      good agreement after 8 weeks of composite formation. The properties of the porous
      titanium-new bone tissue composites can only be predicted when data on the
      properties of new bone tissue are available after 8 weeks of contact between the
      implant and the native bone.

PMID- 25953541
TI  - Water-soluble nanoconjugates of quantum dot-chitosan-antibody for in vitro
      detection of cancer cells based on "enzyme-free" fluoroimmunoassay.
AB  - Cancer remains one of the world's most devastating diseases with millions of
      fatalities and new cases every year. In this work, we attempted to develop a
      facile "enzyme-free" fluoroimmunoassay based on the novel nanoconjugates composed
      of CdS quantum dots (QDs) as the fluorescent inorganic core and an antibody
      modified polysaccharide as the organic shell, modeling their possible application
      for the in vitro diagnosis of non-Hodgkin lymphoma (NHL) cancer. Chitosan was
      conjugated with an anti-CD20 polyclonal antibody (pAbCD20) by the formation of
      covalent amide bonds. In the sequence, these chitosan-antibody conjugates were
      utilized as direct ligands for the surface biofunctionalization of CdS QDs
      (CdS/chitosan-pAbCD20) using a single-step colloidal process in aqueous medium at
      room temperature. The most relevant physico-chemical properties of these
      nanoconjugates were assessed by morphological and spectroscopic techniques. The
      results indicated that CdS nanocrystals were produced with an average diameter of
      2.5 nm and with cubic zinc blende crystalline nanostructure. The CdS
      immunoconjugates (CdS/chitosan-pAbCD20) presented colloidal hydrodynamic diameter
      (HD) of 15.0 +/- 1.2n m. In addition, the results evidenced that the "enzyme
      free" QD-linked immunosorbent assay (QLISA) was effective for the in vitro
      detection against the antigen CD20 (aCD20) based on fluorescent behavior of the
      CdS nanoconjugates. Moreover, the CdS-immunoconjugates were successfully used for
      fluorescence bioimaging of NHL cancer cells. Finally, the cell viability results
      using different cell cultures based on LDH, MTT and Resazurin bio-assays have
      demonstrated no cytotoxicity of the new CdS-chitosan bioconjugates relative to
      the standard controls. Thus, CdS conjugates may offer a promising platform for
      the future development of in vitro and in vivo applications for the detection and
      diagnosis of NHL cancer cells.

PMID- 25953542
TI  - Design and characterization of antimicrobial usnic acid loaded-core/shell
      magnetic nanoparticles.
AB  - The application of magnetic nanoparticles (MNPs) in medicine is considered much
      promising especially because they can be handled and directed to specific body
      sites by external magnetic fields. MNPs have been investigated in magnetic
      resonance imaging, hyperthermia and drug targeting. In this study, properly
      functionalized core/shell MNPs with antimicrobial properties were developed to be
      used for the prevention and treatment of medical device-related infections.
      Particularly, surface-engineered manganese iron oxide MNPs, produced by a micro
      emulsion method, were coated with two different polymers and loaded with usnic
      acid (UA), a dibenzofuran natural extract possessing antimicrobial activity.
      Between the two polymer coatings, the one based on an intrinsically antimicrobial
      cationic polyacrylamide (pAcDED) resulted to be able to provide MNPs with proper
      magnetic properties and basic groups for UA loading. Thanks to the establishment
      of acid-base interactions, pAcDED-coated MNPs were able to load and release
      significant drug amounts resulting in good antimicrobial properties versus
      Staphylococcus epidermidis (MIC = 0.1 mg/mL). The use of pAcDED having intrinsic
      antimicrobial activity as MNP coating in combination with UA likely contributed
      to obtain an enhanced antimicrobial effect. The developed drug-loaded MNPs could
      be injected in the patient soon after device implantation to prevent biofilm
      formation, or, later, in presence of signs of infection to treat the biofilm
      grown on the device surfaces.

PMID- 25953543
TI  - Ultrasonic assisted removal of sunset yellow from aqueous solution by zinc
      hydroxide nanoparticle loaded activated carbon: Optimized experimental design.
AB  - The efficiency of zinc hydroxide nanoparticle loaded on activated carbon (Zn(OH)2
      NP-AC) in the removal of sunset yellow from aqueous solutions using ultrasonic
      assisted adsorption method was investigated. This nanomaterial was characterized
      using different techniques such as SEM, XRD and UV-vis spectrophotometer. A
      central composite design (CCD) was used for the optimization of significant
      factors using response surface methodology (RSM). Under the best conditions (5.2
      min of sonication time, pH3, 0.023 g of adsorbent and 30 mg L(-1) of SY),
      Langmuir model was fitting the experimental equilibrium data well. The small
      amount of proposed adsorbent (0.023 g) is applicable for the successful removal
      of SY (>97%) in short time (5 min) with high adsorption capacity (83-114 mg g(
      1)).

PMID- 25953544
TI  - Silk fibroin/gelatin-chondroitin sulfate-hyaluronic acid effectively enhances in
      vitro chondrogenesis of bone marrow mesenchymal stem cells.
AB  - Tissue engineering is becoming promising for cartilage repair due to the limited
      self-repair capacity of cartilage tissue. We previously fabricated and
      characterized a three-dimensional silk fibroin/gelatin-chondroitin sulfate
      hyaluronic acid (SF-GCH) scaffold and showed that it could promote proliferation
      of human bone marrow mesenchymal stem cells (BM-MSCs). This study aimed to
      evaluate its biological performance as a new biomimetic material for chondrogenic
      induction of BM-MSCs in comparison to an SF scaffold and conventional pellet
      culture. We found that the SF-GCH scaffold significantly enhanced the
      proliferation and chondrogenic differentiation of BM-MSCs compared to the SF
      scaffold and pellet culture in which the production of sulfated glycoaminoglycan
      was increased in concordance with the up-regulation of chondrogenic-specific gene
      markers. Our findings indicate the significant role of SF-GCH by providing a
      supportive structure and the mimetic cartilage environment for chondrogenesis
      which enables cartilage regeneration. Thus, our fabricated SF-GCH scaffold may
      serve as a potential biomimetic material for cartilage tissue engineering. 

PMID- 25953546
TI  - A sensitive electrochemical sensor for determination of gallic acid based on SiO2
      nanoparticle modified carbon paste electrode.
AB  - Gallic acid (GA), one of the main phenolic components, has been a subject of
      increasing interest due to their biological properties, including anti
      inflammatory, antihistaminic, and antitumor activities, scavenging of free
      radicals, and protecting against cardiovascular diseases. Therefore, developing
      sensitive and selective sensor for GA is very important and interesting. Herein,
      SiO2 nanoparticles were synthesized and then used to prepare a modified carbon
      paste electrode (CPE) for determination of GA. For better comparison, multiwalled
      carbon nanotubes (MWCNTs) and graphite were also employed to prepare an
      electrochemical sensor for determination of GA. The electrochemical behaviors of
      GA at different electrochemical sensors were investigated. Compared with other
      sensors, the SiO2 nanoparticle sensor greatly enhances the response signal of GA
      due to the large active surface area and high accumulation efficiency.
      Voltammetric studies show that the SiO2 nanoparticle modified carbon paste
      electrode is sensitive to GA in the concentration range of 8.0 * 10(-7) to 1.0 *
      10(-4) mol L(-1), and the limit of detection and sensitivity were calculated as
      2.5 * 10(-7) mol L(-1) and 1790.7 (MUA/mM), respectively. Finally, the proposed
      electrochemical sensor was successfully employed to determine GA in tea and
      orange juice samples.

PMID- 25953545
TI  - Fluorescent probe based on heteroatom containing styrylcyanine: pH-sensitive
      properties and bioimaging in vivo.
AB  - A novel fluorescent probe based on heteroatom containing styrylcyanine is
      synthesized. The fluorescence of probe is bright green in basic and neutral media
      but dark orange in strong acidic environments, which could be reversibly
      switched. Such behavior enables it to work as a fluorescent pH sensor in the
      solution state and a chemosensor for detecting acidic and basic volatile organic
      compounds. Analyses by NMR spectroscopy confirm that the protonation or
      deprotonation of pyridinyl moiety is responsible for the sensing process. In
      addition, the fluorescent microscopic images of probe in live cells and zebrafish
      are achieved successfully, suggesting that the probe has good cell membrane
      permeability and low cytotoxicity. 

PMID- 25953547
TI  - Poly-L-lactide/sodium alginate/chitosan microsphere hybrid scaffolds made with
      braiding manufacture and adhesion technique: Solution to the incongruence between
      porosity and compressive strength.
AB  - Bone scaffolds require a three-dimensional structure, high porosity,
      interconnected pores, adequate mechanical strengths, and non-toxicity. A high
      porosity is incongruent with mechanical strengths. Therefore, this study combines
      a braiding method and microsphere solution to create bone scaffolds with a high
      porosity and sufficient mechanical strengths. First, poly-L-lactide (PLLA) plied
      yarns are braided into 5-, 10-, 15-, 20-, and 25-layer hollow braids, and then
      thermally treated at 165  degrees C for various durations. Next, sodium alginate
      (SA) microspheres, cross-linked with CaCl2 solution with various concentrations,
      are combined with PLLA porous braided bone scaffolds to form PLLA/SA/CS
      microsphere hybrid scaffolds, which are then observed for surface observation,
      and tested for porosity, water contact angle, compressive strength, MTT assay,
      bioactivity, alkaline phosphatase (ALP) assay, cell attachment, and statistical
      analyses. The test results show that the layer amount of the bone scaffold is
      proportional to the compressive strength. With the same number of layers, the
      compressive strength is inversely proportional to the concentration of the CaCl2
      solution. The results of surface observation, porosity, and water contact angle
      tests show that PLLA/SA/CS microsphere hybrid scaffolds possess a high porosity
      and good hydrophilicity; as a result, the braiding manufacture and the bonding
      technique effectively solve the confliction between porosity and mechanical
      strength. The concentration of CaCl2 does not pertain to cell activity and ALP
      results, exemplified by good cell attachment on bone scaffolds for each
      specification.

PMID- 25953548
TI  - Biocompatible xanthan/polypyrrole scaffolds for tissue engineering.
AB  - Polypyrrole (PPy) was electropolymerized in xanthan hydrogels (XCA), resulting in
      electroactive XCAPPy scaffolds with (15 +/- 3) wt.% PPy and (40 +/- 10) MUm
      thick. The physicochemical characterization of hybrid XCAPPy scaffolds was
      performed by means of cyclic voltammetry, swelling tests, Fourier transform
      infrared spectroscopy (FTIR), differential scanning calorimetry (DSC),
      thermogravimetric analyses (TGA), scanning electron microscopy (SEM), atomic
      force microscopy (AFM) and tensile tests. XCAPPy swelled~80% less than XCA. FTIR
      spectra and thermal analyses did not evidence strong interaction between PPy and
      XCA matrix. XCAPPy presented a porous stratified structure resulting from the
      arrangement of PPy chains parallel to XCA surface. Under stress XCAPPy presented
      larger strain than neat XCA probably due to the sliding of planar PPy chains. The
      adhesion and proliferation of fibroblasts onto XCA and XCAPPy were evaluated in
      the absence and in the presence of external magnetic field (EMF) of 0.4T, after
      one day, 7 days, 14 days and 21 days. Fibroblast proliferation was more
      pronounced onto XCAPPy than onto XCA, due to its higher hydrophobicity and
      surface roughness. EMF stimulated cell proliferation onto both scaffolds.

PMID- 25953549
TI  - The effect of oscillatory mechanical stimulation on osteoblast attachment and
      proliferation.
AB  - The aim of this paper is to investigate the effect of the magnitude and duration
      of oscillatory mechanical stimulation on osteoblast attachment and proliferation
      as well as the time gap between seeding and applying the stimulation. Cells were
      exposed to three levels of speed at two different conditions. For the first
      group, mechanical shear stress was applied after 20 min of cell seeding. For the
      second group there was no time gap between cell seeding and applying mechanical
      stimulation. The total area subjected to shear stress was divided into three
      parts and for each part a comparative study was conducted at defined time points.
      Our results showed that both shear stress magnitude and the time gap between cell
      seeding and applying shear stress, are important in further cell proliferation
      and attachment. The effect of shear stress was not significant at lower speeds
      for both groups at earlier time points. However, a higher percentage of area was
      covered by cells at later time points under shear stress. In addition, the time
      gap can also improve osteoblast attachment. For the best rate of cell attachment
      and proliferation, the magnitude of shear stress and time gap should be
      optimized. The results of this paper can be utilized to improve cell attachment
      and proliferation in bioreactors.

PMID- 25953550
TI  - Influence of the addition of beta-TCP on the morphology, thermal properties and
      cell viability of poly (lactic acid) fibers obtained by electrospinning.
AB  - Electrospinning is a simple and low-cost way to fabricate fibers. Among the
      various polymers used in electrospinning process, the poly (lactic acid) (PLA)
      stands out due to its excellent biodegradability and biocompatibility. Calcium
      phosphate ceramics has been recognized as an attractive biomaterial because their
      chemical composition is similar to the mineral component of the hard tissue in
      the body. Furthermore, they are bioactive and osteoinductive and some are even
      quite biodegradable. The beta-tricalcium phosphate (beta-TCP) particles were
      synthesized by solid state reaction. Different contents of beta-TCP particles
      were incorporated in polymer matrices to form fibers of PLA/beta-TCP composites
      by electrospinning aiming a possible application as a scaffold for tissue
      engineering. The fibers were characterized by scanning electron microscopy (SEM),
      infrared (FTIR), differential scanning calorimetry (DSC) and thermal gravimetric
      analysis (TGA). The average diameter of the fibers varied in the range of 260
      519.6 +/- 50 nm. The presence of beta-TCP particles promoted changes on thermal
      properties of the fibers. The composite with 8 wt-% of beta-TCP showed a low
      degree of crystallinity and can be used for application in tissue engineering.
      The cell viability was analyzed by reduction of the methyl tetrazolium salt by
      the pyruvate dehydrogenase enzymatic complex present in the matrix of
      mitochondria (MTT test). All PLA fiber groups, with different contents of beta
      TCP, showed cytocompatibility ability with non-cytotoxicity effect and bioactive
      properties using SBF assay.

PMID- 25953551
TI  - Improvement of bio-corrosion resistance for Ti42Zr40Si15Ta3 metallic glasses in
      simulated body fluid by annealing within supercooled liquid region.
AB  - The effects of the nanocrystalline phases on the bio-corrosion behavior of highly
      bio-friendly Ti42Zr40Si15Ta3 metallic glasses in simulated body fluid were
      investigated, and the findings are compared with our previous observations from
      the Zr53Cu30Ni9Al8 metallic glasses. The Ti42Zr40Si15Ta3 metallic glasses were
      annealed at temperatures above the glass transition temperature, Tg, with
      different time periods to result in different degrees of alpha-Ti nano-phases in
      the amorphous matrix. The nanocrystallized Ti42Zr40Si15Ta3 metallic glasses
      containing corrosion resistant alpha-Ti phases exhibited more promising bio
      corrosion resistance, due to the superior pitting resistance. This is distinctly
      different from the previous case of the Zr53Cu30Ni9Al8 metallic glasses with the
      reactive Zr2Cu phases inducing serious galvanic corrosion and lower bio-corrosion
      resistance. Thus, whether the fully amorphous or partially crystallized metallic
      glass would exhibit better bio-corrosion resistance, the answer would depend on
      the crystallized phase nature. 

PMID- 25953552
TI  - Non-Faradaic electrochemical impedance spectroscopy as a reliable and facile
      method: Determination of the potassium ion concentration using a guanine rich
      aptasensor.
AB  - In this article we report the application of non-Faradaic mode of electrochemical
      impedance spectroscopy (EIS) for determination of potassium ion (K(+))
      concentration using a guanine rich K(+)-selective aptasensor (K(+)-aptasensor).
      This is a simple, electroactive probe free, sensitive and reproducible method
      allowing determination of K(+) ion concentration without any disturbance from
      electroactive probes used in similar works based on the Faradaic EIS method.
      Herein, a wide linear range of K(+) ion concentrations (1 MUM-0.1mM) with a 200
      nM limit of detection was achieved which is better than most of the previously
      reported Faradaic biosensing methods. The proposed method maintains valuable
      applications when it is used for K(+) determination in the presence of
      potentially important interferences in biological media. Thus, application of the
      non-Faradaic EIS method for sensing the concentration of K(+) ion with the
      presented K(+)-aptasensor can find an important role in clinical assay.

PMID- 25953553
TI  - Collagen/chitosan based two-compartment and bi-functional dermal scaffolds for
      skin regeneration.
AB  - Inspired from the sophisticated bilayer structures of natural dermis, here, we
      reported collagen/chitosan based two-compartment and bi-functional dermal
      scaffolds. Two functions refer to mediating rapid angiogenesis based on
      recombinant human vascular endothelial growth factor (rhVEGF) and antibacterial
      from gentamicin, which were encapsulated in PLGA microspheres. The gentamicin and
      rhVEGF encapsulated PLGA microspheres were further combined with
      collagen/chitosan mixtures in low (lower layer) and high (upper layer)
      concentrations, and molded to generate the two-compartment and bi-functional
      scaffolds. Based on morphology and pore structure analyses, it was found that the
      scaffold has a distinct double layered porous and connective structure with PLGA
      microspheres encapsulated. Statistical analysis indicated that the pores in the
      upper layer and in the lower layer have great variations in diameter, indicative
      of a two-compartment structure. The release profiles of gentamicin and rhVEGF
      exceeded 28 and 49 days, respectively. In vitro culture of mouse fibroblasts
      showed that the scaffold can facilitate cell adhesion and proliferation.
      Moreover, the scaffold can obviously inhibit proliferation of Staphylococcus
      aureus and Serratia marcescens, exhibiting its unique antibacterial effect. The
      two-compartment and bi-functional dermal scaffolds can be a promising candidate
      for skin regeneration.

PMID- 25953554
TI  - Polyurethane/polylactide-based biomaterials combined with rat olfactory bulb
      derived glial cells and adipose-derived mesenchymal stromal cells for neural
      regenerative medicine applications.
AB  - Research concerning the elaboration and application of biomaterial which may
      support the nerve tissue regeneration is currently one of the most promising
      directions. Biocompatible polymer devices are noteworthy group among the numerous
      types of potentially attractive biomaterials for regenerative medicine
      application. Polylactides and polyurethanes may be utilized for developing
      devices for supporting the nerve regeneration, like nerve guide conduits or
      bridges connecting the endings of broken nerve tracts. Moreover, the combination
      of these biomaterial devices with regenerative cell populations, like stem or
      precursor cells should significantly improve the final therapeutic effect.
      Therefore, the composition and structure of final device should support the
      proper adhesion and growth of cells destined for clinical application. In current
      research, the three polymer mats elaborated for connecting the broken nerve
      tracts, made from polylactide, polyurethane and their blend were evaluated both
      for physical properties and in vitro, using the olfactory-bulb glial cells and
      mesenchymal stem cells. The evaluation of Young's modulus, wettability and
      roughness of obtained materials showed the differences between analyzed samples.
      The analysis of cell adhesion, proliferation and morphology showed that the
      polyurethane-polylactide blend was the most neutral for cells in culture, while
      in the pure polymer samples there were significant alterations observed. Our
      results indicated that polyurethane-polylactide blend is an optimal composition
      for culturing and delivery of glial and mesenchymal stem cells. 

PMID- 25953555
TI  - Effect of Mg(2+), Ca(2+), Sr(2+) and Ba(2+) metal ions on the antifungal activity
      of ZnO nanoparticles tested against Candida albicans.
AB  - The antifungal ability of pure and alkaline metal ion (Mg(2+), Ca(2+), Sr(2+) and
      Ba(2+)) doped ZnO nanoparticles (NPs) prepared by the co-precipitation method was
      tested against the pathogenic yeast, Candida albicans (C. albicans), and the
      results showed that the Mg-doped ZnO NPs possessed greater effect than the other
      alkaline metal ion doped ZnO NPs. The impact of the concentration of Mg doped ZnO
      sample on the growth of C. albicans was also studied. The Minimal Fungicidal
      Concentration (MFC) of the Mg doped ZnO NPs was found to be 2000 MUg/ml for which
      the growth of C. albicans was completely inhibited. The ZnO:Mg sample (1.5mg/ml)
      with various concentrations of histidine reduced the fungicidal effect of the
      nanoparticles against C. albicans, which was deliberately explained by the role
      of ROS. The ZnO:Mg sample added with 5mM of histidine scavenged the ample amount
      of generated ROS effectively. The binding of the NPs with fungi was observed by
      their FESEM images and their electrostatic attraction is confirmed by the zeta
      potential measurement.

PMID- 25953556
TI  - Polyglycidyl methacrylate based immunoaffinity cryogels for insulin adsorption.
AB  - Immunoaffinity chromatography (IAC) is a kind of bioaffinity chromatography which
      used antibodies or antibody-related molecules as the stationary phase. IAC is
      used by many applications for analytical, clinical and diagnostic purposes,
      particularly preferring in analytical purposes on one-step separation and
      purification of target compounds. Moreover, immunoaffinity chromatography is used
      in antibody enrichment and separation of cells. IAC columns are usually applied
      in the antibody experiments due to powerful and selective binding of antibodies
      and/or their target antigens. Antigen or antibody molecules could be immobilized
      to the solid support. Therefore, target antibody or cell is purified. Specific
      bioligands can be immobilized directly on glycidyl based polymeric material with
      simple acid-base catalyst. In this study, polyglycidyl methacrylate based
      therefore cryogels were prepared and anti-insulin antibodies were immobilized on
      porous surface of cryogels. Swelling test, Fourier transform infrared
      spectroscopy (FTIR), Raman spectroscopy, and scanning electron microscopy (SEM)
      were conducted to characterize cryogels developed. To optimize separation
      conditions, effects of pH, initial insulin concentration, flow rate, salt
      concentration, contact time and temperature on insulin adsorption capacity were
      examined. The results indicated that the immunoaffinity cryogel developed here
      could be classified as good alternative with prominent properties such as high
      reusability and cost-friendly adsorbent and would be one of the primary reports
      for immunoaffinity purification of insulin molecules in not only lab-scale but
      also for industrial purposes. 

PMID- 25953557
TI  - Unique morphology and gradient arrangement of nacre's platelets in green mussel
      shells.
AB  - Nacre has long served as a classic model in biomineralization and the synthesis
      of biomimetic materials. However, the morphology and arrangement of its basic
      building blocks, the aragonite platelets, are still under hot debate. In this
      study, using a field emission scanning electron microscope (SEM), a high
      resolution transmission electron microscope (HRTEM), and an X-ray diffractometer
      (XRD), we investigate the platelets at the edges and centers of green mussel
      shells. We find that 1) flat and curved platelets coexist in green mussel shells;
      2) the immature platelets at the shell edge are aggregates of aragonite
      nanoparticles, whereas the immature ones at the shell center are single crystals;
      and 3) the morphology and thickness of the platelets exhibit a gradient
      arrangement. Based on these findings, we hypothesize that the gradient in the
      thickness and curvature of the platelets may probably result from the difference
      in growth rate between the edge and the center of the shell and from the gradient
      in compressive stress imposed by the closing of the shells by the adductor
      muscles or the withdrawal of the periostracum by the mantle. We expect that the
      presented results will shed new light on the formation mechanisms of natural
      composite materials. 

PMID- 25953558
TI  - Osteoblast response to porous titanium and biomimetic surface: In vitro analysis.
AB  - OBJECTIVE: This study analyzed the behavior of human osteoblasts cultured on
      porous titanium specimens, with and without biomimetic treatment, compared to
      dense titanium. DESIGN: The experiment had seven groups: Group 1: cells cultured
      on polystyrene of culture plate wells; Group 2: cells cultured on dense titanium
      specimen; Group 3: specimen with 33.79% of pores; Group 4: 41.79% of pores;
      Groups 5, 6 and 7: specimens similar to groups 2, 3 and 4, yet with biomimetic
      treatment. Real time-polymerase chain reaction with reverse transcription of the
      following genes was performed: prostaglandin E2 synthase, integrin beta1,
      osterix, Runx2, Interleukin 6, macrophage colony stimulating factor,
      apolipoprotein E and others. The study achieved data on cell adhesion, growth and
      viability, total protein content, alkaline phosphatase activity and quantity of
      mineralized nodule formations. Data were statistically evaluated. RESULTS:
      Adherent cells and alkaline phosphatase activity were similar in titanium
      specimens, regardless of the groups. Biomimetic treatment reduced the total
      protein activity and the viability of tested cells. Most tested genes had
      statistically similar expression in all groups. CONCLUSION: The tested porosities
      did not cause alterations in osteoblast behavior and the biomimetic treatment
      impaired the biocompatibility of titanium causing cytotoxicity.

PMID- 25953559
TI  - Morphological impact of zinc oxide particles on the antibacterial activity and
      human epithelia toxicity.
AB  - ZnO nanoparticles are utilized in an ever growing number of products and can,
      therefore, be readily encountered in our everyday life. Human beings' outermost
      tissues consist of different epithelia and are, therefore, the most exposed to
      materials from the environment. In this paper, Caco-2 and Calu-3 cell lines were
      used, having been previously broadly applied for in vitro modelling of intestinal
      and respiratory epithelia, respectively. The toxicity of synthesized micro-,
      submicro- and nanoparticulate ZnO on these epithelia was measured and compared to
      the efficacy of the same ZnO particles as antibacterial agents. An approximately
      four-fold excess in antibacterial activity of ZnO nanoparticles over ZnO
      granulate was observed. The results of this paper reveal a sharp distinction
      between toxic nanoparticulate ZnO and safe ZnO particles of larger sizes in
      intestinal and airway in vitro epithelial models. In contrast, ZnO of larger
      particle sizes had only modestly lower antibacterial activity, which can be
      compensated for with higher dosing. These results show that nanoparticulate ZnO
      requires critical in vivo assessment before application. 

PMID- 25953560
TI  - Resorption of monetite calcium phosphate cement by mouse bone marrow derived
      osteoclasts.
AB  - Recently the interest for monetite based biomaterials as bone grafts has
      increased; since in vivo studies have demonstrated that they are degradable,
      osteoconductive and improve bone healing. So far osteoclastic resorption of
      monetite has received little attention. The current study focuses on the
      osteoclastic resorption of monetite cement using primary mouse bone marrow
      macrophages, which have the potential to differentiate into resorbing osteoclasts
      when treated with receptor activator NF-kappaB ligand (RANKL). The osteoclast
      viability and differentiation were analysed on monetite cement and compared to
      cortical bovine bone discs. After seven days live/dead stain results showed no
      significant difference in viability between the two materials. However, the
      differentiation was significantly higher on the bone discs, as shown by tartrate
      resistant acid phosphatase (TRAP) activity and Cathepsin K gene expression.
      Moreover monetite samples with differentiated osteoclasts had a 1.4 fold elevated
      calcium ion concentration in their culture media compared to monetite samples
      with undifferentiated cells. This indicates active resorption of monetite in the
      presence of osteoclasts. In conclusion, this study suggests that osteoclasts have
      a crucial role in the resorption of monetite based biomaterials. It also provides
      a useful model for studying in vitro resorption of acidic calcium phosphate
      cements by primary murine cells. 

PMID- 25953561
TI  - Fabrication of a nonenzymatic glucose sensor using Pd-nanoparticles decorated
      ionic liquid derived fibrillated mesoporous carbon.
AB  - A novel nonenzymatic sensor was developed for glucose detection by the use of
      ionic liquid derived fibrillated mesoporous carbon (IFMC) decorated with
      palladium nanoparticles (PdNPs). PdNPs were uniformly decorated on IFMC and then
      the prepared nano-hybrid material (Pd@IFMC) was drop cast on the surface of a
      glassy carbon electrode to fabricate a glucose sensor. The prepared Pd@IFMC
      showed excellent electrocatalytic activity towards glucose oxidation. An
      oxidation peak at about +0.40 V vs. Ag|AgCl|KClsat was observed for glucose on
      the fabricated sensor in alkaline solution. The oxidation peak current intensity
      was linear towards glucose in the concentration range between 1 and 55 mM (R(2) =
      0.9958) with a detection limit of 0.2 mM. The relative standard deviation (RSD)
      for repetitive measurements (n = 6) of 5 mM of glucose was of 5.3%. The
      fabricated sensor showed a number of great features such as ease of fabrication,
      wide linear range, excellent reproducibility, satisfactory operational stability
      and outstanding resistance towards interfering species such as ascorbic acid,
      uric acid, dopamine, fructose and chloride.

PMID- 25953562
TI  - Osteogenic potential of human adipose-derived stromal cells on 3-dimensional
      mesoporous TiO2 coating with magnesium impregnation.
AB  - The aim of this study was to evaluate the osteogenic response of human adipose
      derived stromal cells (ADScs) to mesoporous titania (TiO2) coatings produced with
      evaporation-induced self-assembly method (EISA) and loaded with magnesium. Our
      emphasis with the magnesium release functionality was to modulate progenitor cell
      osteogenic differentiation under standard culture conditions. Osteogenic
      properties of the coatings were assessed for stromal cells by means of scanning
      electron microscopy (SEM) imaging, colorimetric mitochondrial viability assay
      (MTT), colorimetric alkaline phosphates activity (ALP) assay and real time RT
      polymerase chain reaction (PCR). Using atomic force microscopy (AFM) it was shown
      that the surface expansion area (Sdr) was strongly enhanced by the presence of
      magnesium. From MTT results it was shown that ADSc viability was significantly
      increased on mesoporous surfaces compared to the non-porous one at a longer cell
      culture time. However, no differences were observed between the magnesium
      impregnated and non-impregnated surfaces. The alkaline phosphatase activity
      confirmed that ADSc started to differentiate into the osteogenic phenotype after
      2 weeks of culturing. The gene expression profile at 2 weeks of cell growth
      showed that such coatings were capable to incorporate specific osteogenic markers
      inside their interconnected nano-pores and, at 3 weeks, ADSc differentiated into
      osteoblasts. Interestingly, magnesium significantly promoted the osteopontin gene
      expression, which is an essential gene for the early biomaterial-cell osteogenic
      interaction.

PMID- 25953563
TI  - Development of Fe-based bulk metallic glasses as potential biomaterials.
AB  - A new series of Fe80-x-yCrxMoyP13C7 (x = 10, y = 10; x = 20, y = 5; x = 2 0, y =
      10, all in at.%) bulk metallic glasses (BMGs) with the maximum diameter of 6mm
      have been developed for biomedical implant application by the combination method
      of fluxing treatment and J-quenching technique. The corrosion performance of the
      present Fe-based BMGs is investigated in both Hank's solution (pH = 7.4) and
      artificial saliva solution (pH = 6.3) at 37  degrees C by electrochemical
      measurements. The result indicates that the corrosion resistance of the present
      Fe-based BMGs in the above two simulated body solutions is much better than that
      of biomedical 316 L stainless steel (316 L SS), and approaching that of Ti6Al4V
      biomedical alloy (TC4). The concentrations of Fe, Ni and Cr ions released into
      the Hank's solution and artificial saliva solution from the present Fe-based BMGs
      after potentiodynamic polarization are significant lower than that released from
      316 L SS. The biocompatibility of the present Fe-based BMGs is evaluated through
      the in vitro test of NIH3T3 cells culture in the present Fe-based BMG extraction
      media for 1, 3 and 5 days. The result indicates that the present Fe-based BMGs
      exhibit no cytotoxicity to NIH3T3 cells. And the test result of the cell adhesion
      and growth on the surface of the samples indicates that the present Fe-based BMGs
      exhibit the better cell viability compared with 316 L SS and TC4 biomedical
      alloys. The present Fe-based BMGs, especially Fe55Cr20Mo5P13C7 BMG, exhibit good
      glass formation ability, the high corrosion resistance and excellent
      biocompatibility, suggesting their promising potential as biomaterials.

PMID- 25953564
TI  - Zn and Sr incorporated 64S bioglasses: Material characterization, in-vitro
      bioactivity and mesenchymal stem cell responses.
AB  - Essential element like Zn or Sr is known to play an important role in bone
      remodeling process. In this study, we have used the sol-gel process to synthesize
      the Zn (2%) and Sr (5%) doped 64S bioglasses (BGs, 64SiO2-5P2O5-31CaO, mol.%),
      alone and co-doped. The synthesized glasses were characterized by XRD, FTIR and
      STEM. For biological evaluation, the effects of Zn and Sr incorporation on the in
      vitro bioactivity of the synthesized BGs were studied using the simulated body
      fluid (SBF) soaking. The proliferation and differentiation (ALP, OCN) of rat
      mesenchymal stem cells (MSCs) on these BGs were studied using CCK-8 and ELISA
      analyses. The results indicated that Zn had been uniformly incorporated into the
      bioglass, and demonstrated a stimulating effect on apatite-like layer formation,
      MSC proliferation and differentiation. On the other hand, most of Sr appeared to
      form a secondary crystal phase with extremely high solubility in SBF, showing an
      enhancing effect only in MSC differentiation but not in proliferation, as well as
      an inhibitory effect on apatite-like layer formation. The different dissolution
      behaviors of Sr and Zn ions seemed to have a strong correlation with the
      different apatite-like layer formation capabilities and the cellular responses of
      Zn and Sr containing BGs. 

PMID- 25953565
TI  - Kinetics and thermodynamics studies on the BMP-2 adsorption onto hydroxyapatite
      surface with different multi-morphological features.
AB  - The effect of the surface topography on protein adsorption process is of great
      significance for designing hydroxyapatite (HA) ceramic material surfaces. In this
      work, three different topographies of HA materials HA-sheet, HA-rod, and HA
      whisker were synthesized and testified by X-ray diffraction (XRD), Fourier
      transform infrared (FT-IR), Brunauer-Emmett-Teller (BET) and a field emission
      scanning electron microscopy (FE-SEM). We have systematically investigated the
      adsorption kinetics and thermodynamics of bone morphogenetic proteins (BMP-2) on
      the three different topography surfaces of HA, respectively. The results showed
      that the maximum adsorption capacities of HA-sheet, HA-rod and HA-whisker were
      (219.96 +/- 10.18), (247.13 +/- 12.35), and (354.67 +/- 17.73) MUg . g(-1),
      respectively. Kinetic parameters, rate constants, equilibrium adsorption
      capacities and related correlation coefficients, for each kinetic model were
      calculated as well as discussed. It demonstrated that the adsorption of BMP-2
      onto HA could be described by the pseudo second-order equation. Adsorption of BMP
      2 onto HA followed the Langmuir isotherm. It confirmed that compared with other
      samples HA-whisker had more adsorption sites for its high specific surface area
      which could provide more opportunities for protein molecules. The adsorption
      processes were endothermic (DeltaH > 0), spontaneous (DeltaG < 0) and entropy
      increasing (DeltaS > 0). A possible adsorption mechanism has been proposed. In
      addition, the BMP-2 could be adsorbed to the surface which existed slight
      conformational changes by FT-IR.

PMID- 25953567
TI  - Designing dental composites with bioactive and bactericidal properties.
AB  - OBJECTIVES: The aim of this work was to fabricate and evaluate new antibacterial
      and bioactive composites capable of strictly controlling oral bacteria, enhancing
      apatite layer formation and retaining their mechanical properties. METHODS: A new
      Ag-doped bioactive glass (Ag-BG) was incorporated into flowable dental composite
      (COMP) in different concentrations (1, 5, and 15 wt.%) in order to fabricate new
      combined bioactive and antibacterial composite materials (Ag-BGCOMPs). The
      antibacterial properties, bioactivity, and total bond strength of the Ag-BGCOMPs
      were evaluated. RESULTS: The bioactivity of the Ag-BG was confirmed after its
      immersion in simulated body fluid (SBF). The total bond strength between the
      surrounding tooth tissue and the new composites or the control (dental composite
      alone) has not shown any statistically significant difference in the performed
      pilot study. Antibacterial activity was observed against Escherichia coli (E.
      coli) and Streptococcus mutans (S. mutans) for the Ag-BGCOMP 5 wt.% and 15 wt.%
      but not for the Ag-BGCOMP 1 wt.% or the control. CONCLUSIONS: This work
      contributes to our long term aim which is the fabrication of dental materials
      capable of reducing bacteria invasion and enhancing remineralization of the
      surrounding dental tissues. SIGNIFICANCE: We anticipate that these new composites
      could ultimately prevent restoration failure by inhibiting the formation of
      secondary caries and by remineralizing the hard tissues surrounding tooth
      lesions.

PMID- 25953566
TI  - Enhanced adherence of mouse fibroblast and vascular cells to plasma modified
      polyethylene.
AB  - Since the last decade, tissue engineering has shown a sensational promise in
      providing more viable alternatives to surgical procedures for harvested tissues,
      implants and prostheses. Biomedical polymers, such as low-density polyethylene
      (LDPE), high-density polyethylene (HDPE) and ultra-high molecular weight
      polyethylene (UHMWPE), were activated by Ar plasma discharge. Degradation of
      polymer chains was examined by determination of the thickness of ablated layer.
      The amount of an ablated polymer layer was measured by gravimetry. Contact angle,
      measured by goniometry, was studied as a function of plasma exposure and post
      exposure aging times. Chemical structure of modified polymers was characterized
      by angle resolved X-ray photoelectron spectroscopy. Surface chemistry and
      polarity of the samples were investigated by electrokinetic analysis. Changes in
      surface morphology were followed using atomic force microscopy. Cytocompatibility
      of plasma activated polyethylene foils was studied using two distinct model cell
      lines; VSMCs (vascular smooth muscle cells) as a model for vascular graft testing
      and connective tissue cells L929 (mouse fibroblasts) approved for standardized
      material cytotoxicity testing. Specifically, the cell number, morphology, and
      metabolic activity of the adhered and proliferated cells on the polyethylene
      matrices were studied in vitro. It was found that the plasma treatment caused
      ablation of the polymers, resulting in dramatic changes in their surface
      morphology and roughness. ARXPS and electrokinetic measurements revealed
      oxidation of the polymer surface. It was found that plasma activation has a
      positive effect on the adhesion and proliferation of VSMCs and L929 cells. 

PMID- 25953568
TI  - Microbiological investigations of oxygen plasma treated parylene C surfaces for
      metal implant coating.
AB  - Parylene C surface was modified by the use of oxygen plasma treatment and
      characterized by microscopic and surface-sensitive techniques (E-SEM, AFM, XPS,
      LDI-TOF-MS, contact angle). The influence of the treatment on surface properties
      was investigated by calculations of surface free energy (Owens-Wendt method).
      Moreover, early adhesion (Culture Plate Method, Optical Microscopy Test) and
      biofilm formation ability (Cristal Violet Assay) on the parylene C surface was
      investigated. The bacteria strains which are common causative agents of medical
      device-associated infections (Staphylococcus aureus, Staphylococcus epidermidis
      and Pseudomonas aeruginosa--reference strains and clinical isolates) were used.
      It was concluded that chemical (oxygen insertion) and physical (nanotopography
      generation) changes, have a significant impact on the biocompatibility in terms
      of increased hydrophilicity (theta w of unmodified sample = 88 degrees  +/- 2
      degrees , theta w of 60 min modified sample = 17.6 degrees  +/- 0.8 degrees ) and
      surface free energy (SFE of unmodified sample = 42.4 mJ/m(2), and for 60 min
      modified sample = 70.1 mJ/m(2)). At the same time, no statistical effect on
      biofilm production and bacteria attachment to the modified surface of any of the
      tested strains was observed.

PMID- 25953569
TI  - Antibacterial action of doped CoFe2O4 nanocrystals on multidrug resistant
      bacterial strains.
AB  - The bactericidal effect of pristine and doped cobalt ferrite nanoparticles has
      been evaluated against multiple drug resistant clinical strains by assessing the
      number of colony-forming units (CFU). Monophasic polycrystalline ferrites have
      been prepared by the malate-glycolate sol-gel autocombustion method as confirmed
      by the X-ray diffraction study. Various changes occurring during the preparative
      stages have been demonstrated using TG-DTA analysis which is well complemented by
      the FTIR spectroscopy. The antibacterial studies carried out demonstrate a
      bactericidal effect of the nanoparticles wherein the number of CFU has been found
      to decrease with doping. Cellular distortions have been revealed through SEM.
      Variation in the number of CFU with dopant type has also been reported herein. 

PMID- 25953571
TI  - Electrochemical determination of hydrochlorothiazide and folic acid in real
      samples using a modified graphene oxide sheet paste electrode.
AB  - A new ferrocene-derivative compound, 2-chlorobenzoyl ferrocene, was synthesized
      and used to construct a modified graphene oxide sheet paste electrode. The
      electrooxidation of hydrochlorothiazide at the surface of the modified electrode
      was studied. Under optimized conditions, the square wave voltammetric (SWV) peak
      current of hydrochlorothiazide increased linearly with hydrochlorothiazide
      concentration in the range of 5.0 * 10(-8) to 2.0 * 10(-4) M and a detection
      limit of 20.0 nM was obtained for hydrochlorothiazide. The diffusion coefficient
      and kinetic parameters (such as electron transfer coefficient and the
      heterogeneous rate constant) for hydrochlorothiazide oxidation were also
      determined. The prepared modified electrode exhibits a very good resolution
      between the voltammetric peaks of hydrochlorothiazide and folic acid which makes
      it suitable for the detection of hydrochlorothiazide in the presence of folic
      acid in real samples.

PMID- 25953570
TI  - Determination of Cu(2+), Zn(2+) and Pb(2+) in biological and food samples by FAAS
      after preconcentration with hydroxyapatite nanorods originated from eggshell.
AB  - Hydroxyapatite nanorods (HAPNRs) were prepared from recycled eggshell by using
      precipitation method. The structure of the HAPNRs was physicochemically and
      morphologically characterized by X-ray diffraction, transmission electron
      microscopy and Fourier transform infrared spectroscopy. The resulting HAPNRs were
      used for solid phase extractive preconcentration of Cu(2+), Zn(2+) and Pb(2+)
      prior to its determination by flame atomic absorption spectrometry. Experimental
      variables that influence the quantitative extraction of metal ions were optimized
      by both batch and column methods. The analytes were quantitatively sorbed on the
      matrix between pHs6 and 9. The maximum sorption capacity of the HAPNRs has been
      found to be 2.43, 2.37 and 2.53 mmol g(-1) for Cu(2+), Zn(2+) and Pb(2+),
      respectively, with the preconcentration factor of 250. The 3sigma detection limit
      and 10sigma quantification limit for Cu(2+), Zn(2+) and Pb(2+) were found to be
      0.72, 0.55 and 5.12 MUg L(-1) and 2.40, 1.83 and 17.06 MUg L(-1), respectively.
      The calibration curves were linear up to 250 MUg L(-1) for Cu(2+), 300 MUg L(-1)
      for Zn(2+) and 400 MUg L(-1) for Pb(2+). Accuracy of the proposed method was
      verified using certified reference materials (NCS ZC85006 Tomato, Seronorm Trace
      Elements Whole Blood L-1, Seronorm Trace Elements Whole Blood L-3 and Seronorm
      Trace Elements Urine). The present method was successfully applied to the
      analysis of these metal ions in sea water, biological and food samples.

PMID- 25953572
TI  - Encapsulation and immobilization of papain in electrospun nanofibrous membranes
      of PVA cross-linked with glutaraldehyde vapor.
AB  - In this paper, papain enzyme (E.C. 3.4.22.2, 1.6 U/mg) was successfully
      immobilized in poly(vinyl alcohol) (PVA) nanofibers prepared by electrospinning.
      The morphology of the electrospun nanofibers was characterized by scanning
      electron microscopy (SEM) and the diameter distribution was in the range of 80 to
      170 nm. The presence of the enzyme within the PVA nanofibers was confirmed by
      infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and energy
      dispersive X-ray spectroscopy (EDXS) analyses. The maximum catalytic activity was
      reached when the enzyme loading was 13%. The immobilization of papain in the
      nanofiber membrane was achieved by chemical crosslinking with a glutaraldehyde
      vapor treatment (GAvt). The catalytic activity of the immobilized papain was 88%
      with respect to the free enzyme. The crosslinking time by GAvt to immobilize the
      enzyme onto the nanofiber mat was 24h, and the enzyme retained its catalytic
      activity after six cycles. The crosslinked samples maintained 40% of their
      initial activity after being stored for 14 days. PVA electrospun nanofibers are
      excellent matrices for the immobilization of enzymes due to their high surface
      area and their nanoporous structure.

PMID- 25953573
TI  - Synthesis of L-lysine imprinted cryogels for immunoglobulin G adsorption.
AB  - L-Lysine imprinted poly(2-hydroxyethyl methacrylate-co-N-methacryloyl-L-aspartic
      acid) [P(HEMA-co-MAAsp)] cryogels were synthesized and characterized with Fourier
      transform infrared spectroscopy, scanning electron microscopy, surface area
      measurements, swelling, and squeezing tests. Specific surface area for imprinted
      cryogel was 34.2m(2)/g while the value was 21.3m(2)/g for non-imprinted cryogel.
      IgG adsorption from aqueous solution was examined in continuous mode examining
      the factors effecting adsorption capacity such as pH, concentration, flow rate,
      temperature, ionic strength, and incubation time. 0.5M NaCl was used as
      desorption agent. The IgG adsorption capacity was determined as 55.1 mg/g for 1.0
      mg/mL IgG original concentration at 25.0 degrees C while pH and flow rate were
      7.0 and 0.5 mL/min, respectively. When human serum was used as IgG source, the
      removal of 90.4% of crude IgG was attained for 1/20 diluted plasma sample. The
      imprinted cryogel was used in ten successive cycles without significant loss in
      adsorption capacity. The cryogel was determined to be 1.79 times more selective
      to IgG than albumin and 1.45 times more selective than hemoglobin. The adsorption
      behavior well suited to Langmuir isotherm and the kinetics followed pseudo-second
      order model. Thermodynamic parameters DeltaH degrees , DeltaS degrees  and DeltaG
      degrees  for this adsorption process were also calculated.

PMID- 25953574
TI  - Development of Gd(III) porphyrin-conjugated chitosan nanoparticles as contrast
      agents for magnetic resonance imaging.
AB  - A novel magnetic resonance imaging (MRI) contrast agent based on gadolinium meso
      tetrakis(4-pyridyl)porphyrin [Gd(TPyP)] conjugated with chitosan nanoparticles
      has been developed. The chitosan nanoparticles were synthesized following an
      ionic gelation method and the conditions optimized to generate small
      nanoparticles (CNs) with a narrow size distribution of 35-65 nm. The gadolinium
      meso-tetrakis(4-pyridyl)porphyrin [Gd(TPyP)] was loaded into chitosan
      nanoparticles by passive adsorption. The interaction of chitosan with Gd(TPyP)
      has been examined by UV-visible, Fourier transform infrared spectroscopies (FT
      IR) and inductively coupled plasma mass spectrometry (ICP-MS), which indicate the
      successful association of Gd(TPyP) without any structural distortion throughout
      the chitosan nanoparticles. The potential of Gd(TPyP)-CNs as MRI contrast agent
      has been investigated by magnetic resonance imaging (MRI) in-vitro. Relaxivities
      of Gd(TPyP)-CNs obtained from T1-weighted images, increased with Gd concentration
      and attained an optimum r1 of 38.35 mM(-1) s(-1), which is 12-fold higher
      compared to commercial Gd-DOTA (~4 mM(-1) s(-1) at 3T). The combination of such
      strong MRI contrast with the known properties of porphyrins in photodynamic
      therapy and biocompatibility of chitosan, presents a new perspective in using
      these compounds in cancer theranostics.

PMID- 25953575
TI  - Hybrid scaffold bearing polymer-siloxane Schiff base linkage for bone tissue
      engineering.
AB  - Scaffolds that can provide the requisite biological cues for the fast
      regeneration of bone are highly relevant to the advances in tissue engineering
      and regenerative medicine. In the present article, we report the fabrication of a
      chitosan-gelatin-siloxane scaffold bearing interpolymer-siloxane Schiff base
      linkage, through a single-step dialdehyde cross-linking and freeze-drying method
      using 3-aminopropyltriethoxysilane as the siloxane precursor. Swelling of the
      scaffolds in phosphate buffered saline indicates enhancement with increase in
      siloxane concentration, whereas compressive moduli of the wet scaffolds reveal
      inverse dependence, owing to the presence of siloxane, rich in silanol groups. It
      is suggested that through the strategy of dialdehyde cross-linking, a limiting
      siloxane loading of 20 wt.% into a chitosan -gelatin matrix should be considered
      ideal for bone tissue engineering, because the scaffold made with 30 wt.%
      siloxane loading degrades by 48 wt.%, in 21 days. The hybrid scaffolds bearing
      Schiff base linkage between the polymer and siloxane, unlike the stable linkages
      in earlier reports, are expected to give a faster release of siloxanes and
      enhancement in osteogenesis. This is verified by the in vitro evaluation of the
      hybrid scaffolds using rabbit adipose mesenchymal stem cells, which revealed
      osteogenic cell-clusters on a polymer-siloxane scaffold, enhanced alkaline
      phosphatase activity and the expression of bone-specific genes, whereas the
      control scaffold without siloxane supported more of cell-proliferation than
      differentiation. A siloxane concentration dependent enhancement in osteogenic
      differentiation is also observed.

PMID- 25953576
TI  - The place of direct metal laser sintering (DMLS) in dentistry and the importance
      of annealing.

PMID- 25953577
TI  - Implant site Nexplanon reaction?
AB  - Nexplanon (Schering-Plough Limited/Merck Sharp & Dohme Limited (MSD)) is a long
      active reversible contraceptive method that provides effective contraception for
      3 years. It consists of a single, flexible, rod-shaped implant, containing 68 mg
      etonogestrel. It is 4 cm long, consists of an ethylene vinyl acetate copolymer, a
      non-absorbable material, and also contains 15 mg of barium sulfate, which makes
      it visible by X-ray. We describe a case of a 39-year-old woman who experienced a
      local reaction to the barium sulfate in Nexplanon. She was given medical
      treatment, but only the removal of the implant resolved the symptoms. After
      removal there was gradual improvement and 72 h later the patient was
      asymptomatic. Allergic reaction to barium sulfate is extremely rare: until now,
      there have only been two cases associated with Nexplanon described in the
      literature.

PMID- 25953578
TI  - Forehead necrosis, one of the many facades of giant cell arteritis.
AB  - Giant cell arteritis (GCA) is known to be a potentially blinding condition. Swift
      diagnosis can aid in preventing permanent visual loss and, more importantly,
      protect the contralateral eye. Classical symptoms include jaw claudication,
      myalgia and new-onset headache. We present two cases of GCA with scalp necrosis,
      a rare feature associated with this condition. In the first case, forehead
      necrosis preceded the visual symptoms by 2 days. In the second case it was noted
      a few weeks after the patient presented with profound unilateral loss of vision.
      Scalp necrosis is an important sign that should prompt those approached by these
      patients to consider GCA.

PMID- 25953579
TI  - A middle-aged man presenting with unexplained mucosal erosions and progressive
      dyspnoea.
AB  - Paraneoplastic pemphigus (PNP) is a rare syndrome driven by antibodies (IgG)
      binding to desmogleins and other epidermal proteins leading to skin erosions. In
      rare instances, these same IgG proteins may also target the bronchial mucosa
      leading to an irreversible fibrotic reaction within the epithelium and subsequent
      obstructive lung disease. A 51-year-old man presented to the emergency department
      with 2-3-month history of dyspnoea as well as oral and genital ulcerations and
      inguinal lymphadenopathy. The ulcerations were biopsied and proven to be
      consistent with pemphigus. Subsequent inguinal lymph node biopsy implicated the
      hyaline-vascular variant of Castleman's disease (CD), as the primary cause of the
      patient's pemphigus. The patient underwent pulmonary function testing that
      demonstrated severe airflow obstruction. The patient was diagnosed with PNP and
      associated bronchiolitis obliterans syndrome (BOS). He was treated with rituximab
      for his CD, and oral and inhaled corticosteroids along with azithromycin for his
      BOS. 

PMID- 25953580
TI  - Multivalvular infective endocarditis in pregnancy presenting with septic
      pulmonary emboli.
AB  - A 33-year-old woman presented at 36 weeks gestation with worsening respiratory
      distress. A CT-pulmonary angiogram was performed to rule out a massive pulmonary
      embolism; instead, this identified extensive septic pulmonary emboli throughout
      both lung fields. Given the continuing maternal deterioration, a non-elective
      caesarean section was performed. A transoesophageal echocardiogram identified
      multiple large cardiac valve vegetations on both sides of her heart with an
      associated aortic root abscess. She responded well to a 6-week course of
      intravenous antibiotics.

PMID- 25953581
TI  - Anomalous left anterior descending artery: an uncommon cause of ST elevation
      myocardial infarction.
AB  - A healthy 32-year-old Asian man presented in emergency with a history of severe
      chest pain. ECG showed normal sinus rhythm with ST elevations in the anterior
      chest leads. He was diagnosed with anterior wall ST segment elevation myocardial
      infarction and was thrombolysed with tenecteplase. The cardiac enzymes and
      troponin level were significantly high and echocardiography demonstrated akinetic
      anterior segment of left ventricle. Coronary angiography exhibited anomalous left
      anterior descending artery originating from right sinus of Valsalva without
      atherosclerotic lesion. 

PMID- 25953582
TI  - An unusual case of rapid radiological progression of bullous emphysema secondary
      to severe alpha1-antitrypsin deficiency.

PMID- 25953583
TI  - Propofol extravasation: a rare cause of compartment syndrome.
AB  - We detail a rare cause of forearm compartment syndrome that occurred in an 18
      year-old patient who presented with a Glasgow Coma Scale of 13/15 after a mixed
      drug overdose and subsequently required intubation. She suffered extravasation of
      her propofol infusion, which resulted in intrinsic compression within her forearm
      muscle compartments. Fortunately, the diagnosis of compartment syndrome was made
      swiftly and the patient was taken to theatre within 3 h where she underwent an
      emergency forearm fasciotomy. She made an uneventful recovery and at follow-up
      her wounds had healed well with no associated morbidity or loss of function. The
      learning points of this study highlight the importance of thoroughly
      understanding the signs and symptoms of compartment syndrome while maintaining a
      high index of suspicion. In addition to a thorough history and examination,
      consideration of the potential underlying causes allows for a swifter diagnosis
      and a quicker transition to theatre.

PMID- 25953584
TI  - Thinking outside the box: a middle-aged man with new-onset dyspnoea on exertion
      and pedal oedema.
AB  - We describe a diagnostic dilemma in a middle-aged man presenting with dyspnoea
      and bilateral pedal oedema who had been diagnosed with right heart failure based
      on clinical evidence. The evaluation for aetiology eventually led to discovery of
      an unusual extrathoracic cause, a left-to-right communication in the renal
      vasculature. Renal arteriovenous fistulae are rare and can be congenital,
      acquired or idiopathic. A left-to-right shunt typically presents with high-output
      cardiac failure involving the left and right sides of the heart. An atypical
      feature of this case was the finding of overt right heart failure in the setting
      of a normal left heart. Such a presentation has only been described in a few
      isolated case reports. Diagnostic approaches include CT angiography and cardiac
      catheterisation for haemodynamic measurements. The primary treatment options for
      arteriovenous fistulae are medical management, arterial embolisation and surgical
      repair. 

PMID- 25953585
TI  - A rare cause of aspiration pneumonia.

PMID- 25953586
TI  - Relationship of Various Open Quotients With Acoustic Property, Phonation Types,
      Fundamental Frequency, and Intensity.
AB  - INTRODUCTION: In the present study, we examined the relationship between various
      open quotients (Oqs) and phonation types, fundamental frequency (F0), and
      intensity by multivariate linear regression analysis (MVA) to determine which Oq
      best reflects vocal fold vibratory characteristics. METHODS: Using high-speed
      digital imaging (HSDI), a sustained vowel /e/ at different phonation types, F0s,
      and intensities was recorded from six vocally healthy male volunteers: the types
      of phonation included modal, falsetto, modal breathy, and modal pressed
      phonations; and each phonation was performed at different F0s and intensities.
      Electroglottography (EGG) and sound signals were simultaneously recorded with
      HSDI. From the obtained data, 10 conventional Oqs (four Oqs from the glottal area
      function, four kymographic Oqs, and two EGG-derived Oqs) and two newly introduced
      Oqs (Oq(edge)+ and Oq(edge)) were evaluated. And, relationships between various
      Oqs and phonation types, F0, and intensity were evaluated by MVA. RESULTS: Among
      the various Oqs, Oq(edge)+ and Oq(edge) revealed the strongest correlations with
      an acoustic property and could best describe changes in phonation types: Oq(edge)
      was found to be better than Oq(edge)-. Oq(MLK), the average of five Oqs from five
      line multiline kymography was a very good alternative to Oq(edge)-. EGG-derived
      Oqs were able to differentiate between modal phonation and falsetto phonation,
      but it was necessary to consider the change of F0 simultaneously. MVA showed the
      changes in Oq values between modal and other phonation types, the degree of
      involvement of intensity, and no relationship between F0 and Oqs. CONCLUSIONS:
      Among Oqs evaluated in this study, Oq(edge)+ and Oq(edge) were considered to best
      reflect the vocal fold vibratory characteristics.

PMID- 25953587
TI  - Voice Formants in Individuals With Congenital, Isolated, Lifetime Growth Hormone
      Deficiency.
AB  - OBJECTIVE: To analyze the voice formants (F1, F2, F3, and F4 in Hz) of seven oral
      vowels, in Brazilian Portuguese, [a, epsilon, e, i, o, o, and u] in adult
      individuals with congenital lifetime untreated isolated growth hormone deficiency
      (IGHD). STUDY DESIGN: This is a cross-sectional study. METHODS: Acoustic analysis
      of isolated vowels was performed in 33 individuals with IGHD, age 44.5 (17.6)
      years (16 women), and 29 controls, age 51.1 (17.6) years (15 women). RESULTS:
      Compared with controls, IGHD men showed higher values of F3 [i, e, and epsilon],
      P = 0.006, P = 0.022, and P = 0.006, respectively and F4 [i], P = 0.001 and lower
      values of F2 [u], P = 0.034; IGHD women presented higher values of F1 [i and e] P
      = 0.029 and P = 0.036; F2 [o] P = 0.006; F4 [o] P = 0.031 and lower values of F2
      [i] P = 0.004. IGHD abolished most of the gender differences in formant
      frequencies present in controls. CONCLUSIONS: Congenital, severe IGHD results in
      higher values of most formant frequencies, suggesting smaller oral and pharyngeal
      cavities. In addition, it causes a reduction in the effect of gender on the
      structure of the formants, maintaining a prepubertal acoustic prediction.

PMID- 25953588
TI  - Molecular basis for D- Japanese: identification of novel DEL and D- alleles.
AB  - BACKGROUND AND OBJECTIVES: The occurrence of D- is approximately 0.5% in
      Japanese, but DEL in apparently D- individuals is relatively common compared with
      that in Caucasian populations. On the basis of molecular genetics, we examined D-
      Japanese blood donors. METHODS: A standard serological technique was used for RhD
      typing, and we selected 3526 D- blood samples. Genomic DNA obtained from whole
      blood was used for RHD analysis by polymerase chain reaction (PCR) and
      sequencing. Multiplex PCR to detect all of the RHD exons and use of PCR-sequence
      specific primer (PCR-SSP) to detect RHD deletion (RHD*01N.01) and c.1227G>A
      mutation (for RHD*01EL.01) were performed. RESULTS: Multiplex PCR and PCR-SSP
      revealed that 3091 of 3526 D- individuals (87.7%) were homozygous for RHD*01N.01,
      and 318 individuals (9.0%) had the RHD*01EL.01/RHD*01N.01 or
      RHD*01EL.01/RHD*01EL.01 genotype. The other 103 in the 3526 individuals (2.9%)
      had the known D-CE-D hybrid allele, RHD*01N.04, and the association of RHCE*Ce
      with RHD*01EL.01 as well as RHD*01N.04 was observed. The remaining 14 individuals
      had RHD*01N.01 hemizygous with one of the following alleles: RHD*01N.06 (3),
      RHD*01N.07 (1), RHD*04N.01 (1), RHD*DEL8 (1), RHD with c.761C>G (p.Ser254Ter)
      (2), RHD with c.1252T>A (p.Ter418Lysex26) (2) and apparently common RHD (4).
      Adsorption and elution tests with anti-D revealed that the individuals with
      c.761C>G mutation were D- while the individuals with c.1252T>A mutation were DEL.
      CONCLUSIONS: The RHD genotype of more than 96% of D- Japanese could be determined
      by conventional PCR-SSP. In addition, we identified a novel DEL allele having
      c.1252T>A mutation and a novel RHD silencing allele having c.761C>G nonsense
      mutation.

PMID- 25953592
TI  - Rubrobacter aplysinae sp. nov. isolated from the marine sponge Aplysina
      aerophoba.

PMID- 25953593
TI  - Acinetobacter variabilis sp. nov. (formerly DNA group 15 sensu Tjernberg &
      Ursing), isolated from humans and animals.

PMID- 25953589
TI  - Cytokine-mediated dysregulation of zonula occludens-1 properties in human brain
      microvascular endothelium.
AB  - Zonula occludens-1 (ZO-1) is essential to the proper assembly of interendothelial
      junction complexes that control blood-brain barrier (BBB) integrity. The goal of
      the current paper was to improve our understanding of how proinflammatory
      cytokines modulate ZO-1 properties within the human BBB microvascular
      endothelium. In this respect, we investigated the effects of TNF-alpha and IL-6
      on ZO-1 using human brain microvascular endothelial cells (HBMvECs). Following
      treatment of HBMvECs with either cytokine (0-100 ng/ml, 18 h), we observed
      significantly decreased ZO-1 expression and ZO-1:occludin co-association, in
      parallel with increased ZO-1 phosphorylation (pTyr and pThr). All effects were
      dose-dependent. Either cytokine also caused extensive cell-cell border
      delocalization of ZO-1 in parallel with elevated HBMvEC permeability.
      Furthermore, pre-treatment of HBMvECs with antioxidants (superoxide dismutase,
      catalase, apocynin, N-acetylcysteine), or employing targeted inhibition of NADPH
      oxidase activation (NSC23766, gp91/p47 siRNA), were all found to comparably
      attenuate the cytokine-dependent decrease in ZO-1 protein expression. In summary,
      we present an in vitro model of how different proinflammatory cytokines can
      dysregulate ZO-1 properties in HBMvECs. A causal role for NADPH oxidase
      activation and oxidant signalling is also confirmed. Our findings add mechanistic
      depth to current in vivo models of BBB injury manifesting ZO-1 dysregulation.

PMID- 25953594
TI  - Addressing Neuroplastic Changes in Distributed Areas of the Nervous System
      Associated With Chronic Musculoskeletal Disorders.
AB  - Present interventions utilized in musculoskeletal rehabilitation are guided, in
      large part, by a biomedical model where peripheral structural injury is believed
      to be the sole driver of the disorder. There are, however, neurophysiological
      changes across different areas of the peripheral and central nervous systems,
      including peripheral receptors, dorsal horn of the spinal cord, brain stem,
      sensorimotor cortical areas, and the mesolimbic and prefrontal areas associated
      with chronic musculoskeletal disorders, including chronic low back pain,
      osteoarthritis, and tendon injuries. These neurophysiological changes appear not
      only to be a consequence of peripheral structural injury but also to play a part
      in the pathophysiology of chronic musculoskeletal disorders. Neurophysiological
      changes are consistent with a biopsychosocial formulation reflecting the
      underlying mechanisms associated with sensory and motor findings, psychological
      traits, and perceptual changes associated with chronic musculoskeletal
      conditions. These changes, therefore, have important implications in the clinical
      manifestation, pathophysiology, and treatment of chronic musculoskeletal
      disorders. Musculoskeletal rehabilitation professionals have at their disposal
      tools to address these neuroplastic changes, including top-down cognitive-based
      interventions (eg, education, cognitive-behavioral therapy, mindfulness
      meditation, motor imagery) and bottom-up physical interventions (eg, motor
      learning, peripheral sensory stimulation, manual therapy) that induce
      neuroplastic changes across distributed areas of the nervous system and affect
      outcomes in patients with chronic musculoskeletal disorders. Furthermore, novel
      approaches such as the use of transcranial direct current stimulation and
      repetitive transcranial magnetic stimulation may be utilized to help renormalize
      neurological function. Comprehensive treatment addressing peripheral structural
      injury as well as neurophysiological changes occurring across distributed areas
      of the nervous system may help to improve outcomes in patients with chronic
      musculoskeletal disorders. 

PMID- 25953595
TI  - Health, Personal, and Environmental Predictors of Wheelchair-Use Confidence in
      Adult Wheelchair Users.
AB  - BACKGROUND: There are no predictive models of wheelchair-use confidence.
      Therefore, clinicians and researchers are limited in their ability to screen for
      and identify wheelchair users who may be more prone to low wheelchair-use
      confidence and may benefit from clinical intervention. OBJECTIVE: The purpose of
      this study was to identify health-related, personal, and environmental factors
      that predict perceived wheelchair-use confidence in community-dwelling adults who
      use manual wheelchairs. DESIGN: A cross-sectional study was conducted. METHODS:
      Community-dwelling manual wheelchair users (N=124) were included in the study if
      they were >=50 years of age, had >=6 months of wheelchair use experience, and had
      no cognitive impairment. The Wheelchair Use Confidence Scale was used to assess
      wheelchair-use confidence. The sociodemographic information form, Functional
      Comorbidity Index, Seating Identification Tool, Interpersonal Support and
      Evaluation List, and Home and Community Environment Instrument captured the
      independent variables. Blocks of health, personal, and environmental variables
      were sequentially entered into the regression model. RESULTS: Five personal
      variables (age, standardized beta [beta]=-0.18; sex, beta=-0.26; daily hours of
      wheelchair occupancy, beta=0.20; wheelchair-use training, beta=0.20; and
      wheelchair-use assistance, beta=-0.34) and one environmental variable (need for
      seating intervention, beta=-0.18) were statistically significant predictors,
      explaining 44% of the confidence variance. LIMITATIONS: The sample comprised
      volunteers and, therefore, may underrepresent or overrepresent particular groups
      within the population. The study's cross-sectional research design does not allow
      for conclusions to be made regarding causality. CONCLUSION: Older women who use
      wheelchairs and who require assistance with wheelchair use may have low
      wheelchair-use confidence. The same is true for individuals who have no formal
      wheelchair-use training, who are in need of a seating intervention, and who
      report few hours of daily wheelchair use. These wheelchair users may require
      clinical attention and benefit from intervention.

PMID- 25953596
TI  - Characteristics of Handwriting of People With Cerebellar Ataxia: Three
      Dimensional Movement Analysis of the Pen Tip, Finger, and Wrist.
AB  - BACKGROUND: There are several functional tests for evaluating manual performance;
      however, quantitative manual tests for ataxia, especially those for evaluating
      handwriting, are limited. OBJECTIVE: This study aimed to investigate the
      characteristics of cerebellar ataxia by analyzing handwriting, with a special
      emphasis on correlation between the movement of the pen tip and the movement of
      the finger or wrist. DESIGN: This was an observational study. METHODS: Eleven
      people who were right-handed and had cerebellar ataxia and 17 people to serve as
      controls were recruited. The Scale for the Assessment and Rating of Ataxia was
      used to grade the severity of ataxia. Handwriting movements of both hands were
      analyzed. The time required for writing a character, the variability of
      individual handwriting, and the correlation between the movement of the pen tip
      and the movement of the finger or wrist were evaluated for participants with
      ataxia and control participants. RESULTS: The writing time was longer and the
      velocity profile and shape of the track of movement of the pen tip were more
      variable in participants with ataxia than in control participants. For
      participants with ataxia, the direction of movement of the pen tip deviated more
      from that of the finger or wrist, and the shape of the track of movement of the
      pen tip differed more from that of the finger or wrist. The severity of upper
      extremity ataxia measured with the Scale for the Assessment and Rating of Ataxia
      was mostly correlated with the variability parameters. Furthermore, it was
      correlated with the directional deviation of the trajectory of movement of the
      pen tip from that of the finger and with increased dissimilarity of the shapes of
      the tracks. LIMITATIONS: The results may have been influenced by the scale and
      parameters used to measure movement. CONCLUSIONS: Ataxic handwriting with
      increased movement noise is characterized by irregular pen tip movements
      unconstrained by the finger or wrist. The severity of ataxia is correlated with
      these unconstrained movements.

PMID- 25953597
TI  - Factors influencing the frequency of children's consumption of soft drinks.
AB  - Among other focus areas, interventions designed to improve children's diets need
      to address key factors contributing to children's consumption of sugar-sweetened
      beverages. The present study employed structural equation modelling to
      investigate the relationship between a broad range of predictor variables and the
      frequency with which Australian children consume soft drinks. In total, 1302
      parents of children aged 8 to 14 years responded to an online survey about their
      children's food consumption behaviours. Soft drink consumption frequency was
      primarily influenced by parents' attitudes to soft drinks, children's pestering
      behaviours, and perceived social norms relating to children's consumption of
      these products. Importantly, pestering and social norms had significant direct
      effects on consumption frequency in addition to indirect effects via their impact
      on parents' attitudes to soft drink. 

PMID- 25953598
TI  - Association between meal intake behaviour and abdominal obesity in Spanish
      adults.
AB  - The study aims to evaluate the association between abdominal obesity with meal
      intake behaviour such as having a forenoon meal, having an afternoon meal and
      snacking. This cross-sectional study includes n = 1314 participants aged 20-79
      who were interviewed during the Cardiac health "Semanas del Corazon" events in
      four Spanish cities (Madrid, Las Palmas, Seville and Valencia) in 2008. Waist
      circumference, weight and height were assessed to determine abdominal obesity
      (waist circumference: >=88 cm in women and >=102 cm in men) and BMI,
      respectively. The intake of forenoon and afternoon meal and snacking between the
      participants' regular meals were assessed with a questionnaire that also included
      individual risk factors. The information obtained about diet was required to
      calculate an Unhealthy Habit Score and a score reflecting the Achievement of
      Dietary Guidelines. Adjusted logistic regressions were used to examine the
      association between abdominal obesity and the mentioned meal intake behaviour
      controlling for sex, age, individual risk factors, BMI and diet. Having an
      afternoon meal (OR 0.60; 95% CI (0.41-0.88)) was negatively associated with
      abdominal obesity after adjusting for all confounders, whereas the positive
      association of snacking (OR 1.39; 95% CI (1.05-1.85)) was not independent of BMI
      (OR 1.25; 95% CI (0.84-1.87)). Taking a forenoon meal did not show any
      associations (OR 0.92; 95% CI (0.63-1.34)) with abdominal obesity. The results
      obtained could be helpful in the promotion of healthy habits in nutritional
      education programmes and also in health programmes preventing abdominal obesity.

PMID- 25953599
TI  - Effect of hydration status and fluid availability on ad-libitum energy intake of
      a semi-solid breakfast.
AB  - This study investigated the effects of hydration status and fluid availability on
      appetite and energy intake. Sixteen males completed four 24 h trials, visiting
      the laboratory overnight fasted on two consecutive days. Standardised foods were
      provided during the 24 h and on day two an ad-libitum semi-solid porridge
      breakfast was provided. Water intake during the 24 h (0 or 40 mL?kg(-1)) and
      fluid provision during the ad-libitum breakfast were manipulated so subjects were
      euhydrated with (EU-F) and without fluid (EU-NF) available at breakfast; and
      hypohydrated with (HYPO-F) and without fluid (HYPO-NF) available at breakfast.
      Blood samples (0 and 24 h), urine samples (0-24 h) and subjective responses (0,
      24 and 24.5 h) were collected. HYPO trials decreased body mass by ~1.8%. Serum
      and urine osmolality increased and plasma volume decreased during HYPO trials (P
      <0.001). Total urine output was greater during EU than HYPO trials (P <0.001). Ad
      libitum energy intake was not different between trials: 2658 (938) kJ (EU-F),
      2353 (643) kJ (EU-NF), 2295 (529) kJ (HYPO-F), 2414 (954) kJ (HYPO-NF), (P =
      0.131). Fluid intake was ~200 mL greater during HYPO-F than EU-F (P <0.01). There
      was an interaction effect for thirst (P < 0.001), but not hunger or fullness.
      These results demonstrate that mild hypohydration produced by inadequate fluid
      intake and fluid availability during eating does not influence ad-libitum energy
      intake of a semi-solid breakfast, at least in healthy young males. 

PMID- 25953600
TI  - In search of flavour-nutrient learning. A study of the Samburu pastoralists of
      North-Central Kenya.
AB  - Much of our dietary behaviour is learned. In particular, one suggestion is that
      'flavour-nutrient learning' (F-NL) influences both choice and intake of food. F
      NL occurs when an association forms between the orosensory properties of a food
      and its postingestive effects. Unfortunately, this process has been difficult to
      evaluate because F-NL is rarely observed in controlled studies of adult humans.
      One possibility is that we are disposed to F-NL. However, learning is compromised
      by exposure to a complex Western diet that includes a wide range of energy-dense
      foods. To test this idea we explored evidence for F-NL in a sample of semi
      nomadic pastoralists who eat a very limited diet, and who are lean and food
      stressed. Our Samburu participants (N = 68) consumed a sensory-matched portion
      (400 g) of either a novel low (0.72 kcal/g) or higher (1.57 kcal/g) energy-dense
      semi-solid food on two training days, and an intermediate version on day 3.
      Before and after each meal we measured appetite and assessed expected satiation
      and liking for the test food. We found no evidence of F-NL. Nevertheless, self
      reported measures were very consistent and, as anticipated, expected satiation
      increased as the test food became familiar (expected-satiation drift).
      Surprisingly, we observed insensitivity to the effects of test-meal energy
      density on measures of post-meal appetite. To explore this further we repeated a
      single training day using participants (N = 52) from the UK. Unlike in the
      Samburu, the higher energy-dense meal caused greater suppression of appetite.
      These observations expose interesting cross-cultural differences in sensitivity
      to the energy content of food. More generally, our work illustrates how measures
      can be translated to assess different populations, highlighting the potential for
      further comparisons of this kind. 

PMID- 25953602
TI  - Heme iron polypeptide for the management of anaemia of chronic kidney disease.
AB  - WHAT IS KNOWN AND OBJECTIVE: Anaemia is a common clinical finding among patients
      with chronic kidney disease (CKD) and is associated with significant morbidity
      and healthcare costs. Iron deficiency is an important contributing factor, and
      adequate iron supplementation is essential to optimize the management of anaemia
      of CKD. Oral iron is convenient and inexpensive but is poorly absorbed and
      associated with gastrointestinal distress. Intravenous iron overcomes these
      limitations but is more expensive, requires additional clinical visits for
      administration and is associated with serious adverse events. Oral heme iron
      polypeptide (HIP) is a newer dosage form that has been reported to have higher
      bioavailability and fewer side effects when compared with non-heme iron in
      healthy subjects, but data in patients with CKD are limited. The purpose of this
      review is to evaluate the safety and effectiveness of HIP for the management of
      CKD. METHODS: Searches for PubMed (1947-2015) and International Pharmaceutical
      Abstracts (1970-2015) were conducted using the following terms: heme iron, heme
      iron polypeptide, oral iron, anaemia and chronic kidney disease. The bibliography
      of each relevant article was evaluated for additional studies. Articles were
      selected for review if they were published in the English language and were
      randomized controlled trials evaluating the bioavailability, tolerability or
      efficacy of oral HIP in human subjects with CKD. RESULTS AND DISCUSSION: This
      search yielded three clinical studies. The safety and efficacy of HIP was
      evaluated in a total of 161 subjects with anaemia and various stages of CKD. HIP
      was consistently associated with lower ferritin values when compared with
      traditional iron supplementation. With few exceptions, the effect of HIP on
      haemoglobin, haematocrit, transferrin saturation and recombinant human
      erythropoietin dose, and adverse effects appeared similar to intravenous and oral
      non-heme iron supplementation. The cost of HIP is substantially more than non
      heme iron and comparable to intravenous iron. WHAT IS NEW AND CONCLUSION: Heme
      iron polypeptide does not appear to confer benefit over traditional iron
      supplementation among patients with anaemia of CKD and is more expensive.

PMID- 25953601
TI  - Mindless feeding: Is maternal distraction during bottle-feeding associated with
      overfeeding?
AB  - Mindless eating, or eating while distracted by surrounding stimuli, leads to
      overeating. The present study explored whether "mindless feeding," or maternal
      distraction during bottle-feeding, is associated with greater infant formula/milk
      intakes and lower maternal sensitivity to infant cues. Mothers and their <=24
      week-old bottle-feeding infants (N = 28) visited our laboratory for a video
      recorded feeding observation. Infant intake was assessed by weighing bottles
      before and after the feedings. Maternal sensitivity to infant cues was
      objectively assessed by behavioral coding of video-records using the Nursing
      Child Assessment Feeding Scale. Maternal distraction was defined as looking away
      from the infant >75% of the feeding; using a mobile device; conversing with
      another adult; or sleeping. Twenty-nine percent (n = 8) of mothers were
      distracted. While differences in intakes for infants of distracted vs. not
      distracted mothers did not reach significance (p = 0.24), the association between
      distraction and infant intake was modified by two dimensions of temperament:
      orienting/regulation capacity (p = 0.03) and surgency/extraversion (p = 0.04).
      For infants with low orienting/regulation capacity, infants of distracted mothers
      consumed more (177.1 +/- 33.8 ml) than those of not distracted mothers (92.4 +/-
      13.8 ml). Similar findings were noted for infants with low surgency/extraversion
      (distracted: 140.6 +/- 22.5 ml; not distracted: 78.4 +/- 14.3 ml). No association
      between distraction and intake was seen for infants with high
      orienting/regulation capacity or surgency/extraversion. A significantly greater
      proportion of distracted mothers showed low sensitivity to infant cues compared
      to not distracted mothers (p = 0.04). In sum, mindless feeding may interact with
      infant characteristics to influence feeding outcomes; further experimental and
      longitudinal studies are needed. 

PMID- 25953604
TI  - Luminescence and Electronic Spectral Studies of Some Synthesized Lanthanide
      Complexes Using Benzoic Acid Derivative and o-Phenanthroline.
AB  - Lanthanide complexes of p-nitrobenzoic acid(p-NBA) and o-phenanthroline(o-phen)
      namely [Ln2(Phen)2(p-NBA)3(NO3)2].2H2O where, Ln = Sm(III),Tb(III),Dy(III) and
      [Eu2(Phen)2(p-NBA)3].4H2O were synthesized and further characterized by Elemental
      analysis, UV spectroscopy, IR spectroscopy, (1)HNMR spectroscopy. Luminescence
      measurements were performed on all compounds in ethanolic solution. These
      complexes have showed narrow emission indicating that the organic ligands are
      better energy absorber and capable of transferring energy to the Ln (III) ion.
      Furthermore, we reported electronic spectral studies on [Eu2 (Phen)2 (p
      NBA)3].4H2O in order to calculate following parameters, viz: Oscillator strength
      (f), Judd-Ofelt parameters Omegalambda (lambda = 2,4,6) and Radiative parameters.
      [Eu2 (o-Phen)2 (p-NBA)3].4H2O showed the strongest emission at 613 nm corresponds
      to (5)D0->(7)F2 hypersensitive transition, this emission is very sensitive to the
      environment. However, the larger value of Omega2 supports the presence of the
      hypersensitive transition (5)D0->(7)F2 which strictly depends on the nature of
      ligand. All electronic spectral parameters were calculated systemically. 

PMID- 25953603
TI  - The prevalence, incidence, management and risks of atrial fibrillation in an
      elderly Chinese population: a prospective study.
AB  - BACKGROUND: There is limited information on prevalent and incident atrial
      fibrillation in Chinese. We aimed to investigate the prevalence, incidence,
      management and risks of atrial fibrillation in an elderly Chinese population.
      METHODS: In a population--based prospective study in elderly (>= 60 years)
      Chinese, we performed cardiovascular health examinations including a 12-lead
      electrocardiogram at baseline in 3,922 participants and biennially during follow
      up in 2,017 participants. We collected information on vital status during the
      whole follow-up period. RESULTS: The baseline prevalence of atrial fibrillation
      was 2.0 % (n = 34) in 1718 men and 1.6 % (n = 36) in 2204 women. During a median
      3.8 years of follow-up, the incidence rate of atrial fibrillation (n = 34) was
      4.9 per 1000 person-years (95 % confidence interval [CI], 3.4-6.9). In univariate
      analysis, both the prevalence and incidence of atrial fibrillation were higher
      with age advancing (P < 0.0001) and in the presence of coronary heart disease (P
      <= 0.02). Of the 104 prevalent and incident cases of atrial fibrillation, only 1
      (1.0 %) received anticoagulant therapy (warfarin). These patients with atrial
      fibrillation, compared with those with sinus rhythm, had significantly higher
      risks of all-cause (n = 261, hazard ratio [HR] 1.87, 95 % CI, 1.09-3.20, P =
      0.02), cardiovascular (n = 136, HR 3.78, 95 % CI 2.17-6.58, P < 0.0001) and
      stroke mortality (n = 44, HR 6.31, 95 % CI 2.81-14.19, P = 0.0003). CONCLUSIONS:
      Atrial fibrillation was relatively frequent in elderly Chinese, poorly managed
      and associated with higher risks of mortality.

PMID- 25953605
TI  - A Novel Label-Free microRNA-155 Detection on the Basis of Fluorescent Silver
      Nanoclusters.
AB  - In this paper, a new approach for microRNA-155 (miRNA-155) detection was
      described based on the fluorescence quenching of oligonucleotide-templated silver
      nanoclusters (DNA-AgNCs). The specific DNA scaffold with two different
      nucleotides fragments were used: one was enriched with a cytosine sequence
      fragment (C12) that could result in DNA-AgNCs with a high quantum yield via a
      chemical reduction method, and the other was the probe fragment (5-
      CUGUUAAUGCUAAUCGUG-3) which could selectively bind to the miRNA-155. Thus, the as
      prepared AgNCs could exhibit quenched fluorescence when binding to the target
      miRNA-155. The fluorescence ratio of the DNA-AgNCs was quenched in a linearly
      proportional manner to the concentration of the target in the range of 0.2 nM to
      30 nM with a detection limit of 0.1 nM. 

PMID- 25953606
TI  - Integrated ecological risk assessment of dioxin compounds.
AB  - Current ecological risk assessment (ERA) schemes focus mainly on bioaccumulation
      and toxicity of pollutants in individual organisms. Ecological models are tools
      mainly used to assess ecological risks of pollutants to ecosystems, communities,
      and populations. Their main advantage is the relatively direct integration of the
      species sensitivity to organic pollutants, the fate and mechanism of action in
      the environment of toxicants, and life-history features of the individual
      organism of concern. To promote scientific consensus on ERA schemes, this review
      is intended to provide a guideline on short-term ERA involving dioxin chemicals
      and to identify key findings for exposure assessment based on policies of
      different agencies. It also presents possible adverse effects of dioxins on
      ecosystems, toxicity equivalence methodology, environmental fate and transport
      modeling, and development of stressor-response profiles for dioxin-like
      chemicals. 

PMID- 25953607
TI  - Comparison of the MBBR denitrification carriers for advanced nitrogen removal of
      wastewater treatment plant effluent.
AB  - The moving bed biofilm reactors (MBBRs) were used to remove the residual NO3(-)-N
      of wastewater treatment plant (WWTP) effluent, and the MBBR carriers for
      denitrification were compared. The results showed that high denitrification
      efficiency can be achieved with polyethylene, polypropylene, polyurethane foam,
      and haydite carriers under following conditions: 7.2 to 8.0 pH, 24 to 26  degrees
      C temperature, 12 h hydraulic retention time (HRT), and 25.5 mg L(-1) external
      methanol dosage, while the WWTP effluent total nitrogen (TN) was between 2.6 and
      15.4 mg L(-1) and NO3(-)-N was between 0.2 and 12.6 mg L(-1). The MBBR filled
      with polyethylene carriers had higher TN and NO3(-)-N removal rate (44.9 +/- 19.1
      and 83.4 +/- 13.0%, respectively) than those with other carriers. The minimum
      effluent TN and NO3(-)-N of polyethylene MBBR were 1.6 and 0.1 mg L(-1),
      respectively, and the maximum denitrification rate reached 23.0 g m(-2) day(-1).
      When chemical oxygen demand (COD)/TN ratio dropped from 6 to 4, the NO3(-)- N and
      TN removal efficiency decreased significantly in all reactors except for that
      filled with polyethylene, which indicated that the polyethylene MBBR can resist
      influent fluctuation much better. The three-dimensional excitation-emission
      matrix analysis showed that all the influent and effluent of MBBRs contain
      soluble microbial products (SMPs)-like organics and biochemical oxygen demand
      (BOD), which can be removed better by MBBRs filled with haydite and polyethylene
      carriers. The nitrous oxide reductase (nosZ)-based terminal restriction fragment
      length polymorphism (T-RFLP) analysis suggested that the dominant bacteria in
      polyethylene MBBR are the key denitrificans.

PMID- 25953608
TI  - Ecotoxicology is not normal: A comparison of statistical approaches for analysis
      of count and proportion data in ecotoxicology.
AB  - Ecotoxicologists often encounter count and proportion data that are rarely
      normally distributed. To meet the assumptions of the linear model, such data are
      usually transformed or non-parametric methods are used if the transformed data
      still violate the assumptions. Generalized linear models (GLMs) allow to directly
      model such data, without the need for transformation. Here, we compare the
      performance of two parametric methods, i.e., (1) the linear model (assuming
      normality of transformed data), (2) GLMs (assuming a Poisson, negative binomial,
      or binomially distributed response), and (3) non-parametric methods. We simulated
      typical data mimicking low replicated ecotoxicological experiments of two common
      data types (counts and proportions from counts). We compared the performance of
      the different methods in terms of statistical power and Type I error for
      detecting a general treatment effect and determining the lowest observed effect
      concentration (LOEC). In addition, we outlined differences on a real-world
      mesocosm data set. For count data, we found that the quasi-Poisson model yielded
      the highest power. The negative binomial GLM resulted in increased Type I errors,
      which could be fixed using the parametric bootstrap. For proportions, binomial
      GLMs performed better than the linear model, except to determine LOEC at
      extremely low sample sizes. The compared non-parametric methods had generally
      lower power. We recommend that counts in one-factorial experiments should be
      analyzed using quasi-Poisson models and proportions from counts by binomial GLMs.
      These methods should become standard in ecotoxicology. 

PMID- 25953609
TI  - Non-parametric kernel density estimation of species sensitivity distributions in
      developing water quality criteria of metals.
AB  - Due to use of different parametric models for establishing species sensitivity
      distributions (SSDs), comparison of water quality criteria (WQC) for metals of
      the same group or period in the periodic table is uncertain and results can be
      biased. To address this inadequacy, a new probabilistic model, based on non
      parametric kernel density estimation was developed and optimal bandwidths and
      testing methods are proposed. Zinc (Zn), cadmium (Cd), and mercury (Hg) of group
      IIB of the periodic table are widespread in aquatic environments, mostly at small
      concentrations, but can exert detrimental effects on aquatic life and human
      health. With these metals as target compounds, the non-parametric kernel density
      estimation method and several conventional parametric density estimation methods
      were used to derive acute WQC of metals for protection of aquatic species in
      China that were compared and contrasted with WQC for other jurisdictions. HC5
      values for protection of different types of species were derived for three metals
      by use of non-parametric kernel density estimation. The newly developed
      probabilistic model was superior to conventional parametric density estimations
      for constructing SSDs and for deriving WQC for these metals. HC5 values for the
      three metals were inversely proportional to atomic number, which means that the
      heavier atoms were more potent toxicants. The proposed method provides a novel
      alternative approach for developing SSDs that could have wide application
      prospects in deriving WQC and use in assessment of risks to ecosystems. 

PMID- 25953611
TI  - In autoimmune hepatitis type 1 or the autoimmune hepatitis-sclerosing cholangitis
      variant defective regulatory T-cell responsiveness to IL-2 results in low IL-10
      production and impaired suppression.
AB  - Defective immune regulation plays a permissive role enabling effector cells to
      initiate and perpetuate tissue damage, eventually resulting in autoimmune
      disease. Numerical and functional regulatory T-cell (Treg) impairment has been
      previously reported in autoimmune liver disease (AILD; including autoimmune
      hepatitis and autoimmune sclerosing cholangitis ASC). However, in these early
      reports, Tregs were phenotypically defined as CD4(+) CD25(+) or CD4(+) CD25(high)
      cells. In the current study, we reexamined phenotypic and functional properties
      of Tregs by adopting a more refined definition of these cells that also includes
      negativity or low level of expression of CD127. We studied 43 AILD patients and
      22 healthy subjects (HSs) and found that CD4(+) CD25(+) CD127(-) Tregs were
      decreased in the former. This decrease was more marked in patients with active
      disease than in those in remission. In AILD, Treg frequencies correlated
      inversely with parameters of disease activity and were not affected by
      immunosuppressive treatment. We also document, for the first time, that, in AILD,
      bona-fide Tregs produce less interleukin (IL)-10 and are impaired in their
      ability to suppress CD4(+) CD25(-) target cell proliferation, a feature that in
      HSs, but not in AILDs, is dependent, at least in part, on IL-10 secretion.
      Decreased IL-10 production by Tregs in AILD is linked to poor responsiveness to
      IL-2 and phospho signal transducer and activator of transcription 5 up
      regulation. CONCLUSION: Tregs are numerically impaired in AILD, this impairment
      being more prominent during active disease. Notably, defective IL-10 production,
      resulting from low Treg responsiveness to IL-2, contributes to Treg functional
      impairment.

PMID- 25953610
TI  - Biosorption of Cu(II) by immobilized microalgae using silica: kinetic,
      equilibrium, and thermodynamic study.
AB  - Immobilized microalgae using silica (IMS) from Micractinium reisseri KGE33 was
      synthesized through a sol-gel reaction. Green algal waste biomass, the residue of
      M. reisseri KGE33 after oil extraction, was used as the biomaterial. The
      adsorption of Cu(II) on IMS was tested in batch experiments with varying algal
      doses, pH, contact times, initial Cu(II) concentrations, and temperatures. Three
      types of IMSs (IMS 14, 70, and 100) were synthesized according to different algal
      doses. The removal efficiency of Cu(II) in the aqueous phase was in the following
      order: IMS 14 (77.0%) < IMS 70 (83.3%) < IMS 100 (87.1%) at pH 5. The point of
      zero charge (PZC) value of IMS100 was 4.5, and the optimum pH for Cu(II)
      adsorption was 5. Equilibrium data were described using a Langmuir isotherm
      model. The Langmuir model maximum Cu(II) adsorption capacity (q m) increased with
      the algal dose in the following order: IMS 100 (1.710 mg g(-1)) > IMS 70 (1.548
      mg g(-1)) > IMS 14 (1.282 mg g(-1)). The pseudo-second-order equation fitted the
      kinetics data well, and the value of the second-order rate constant increased
      with increasing algal dose. Gibbs free energies (DeltaG degrees ) were negative
      within the temperature range studied, which indicates that the adsorption process
      was spontaneous. The negative value of enthalpy (DeltaH degrees ) again indicates
      the exothermic nature of the adsorption process. In addition, SEM-energy
      dispersive X-ray spectroscopy (EDS), Fourier transform infrared (FT-IR), and X
      ray photoelectron spectroscopy (XPS) analyses of the IMS surface reveal that the
      algal biomass on IMS is the main site for Cu(II) binding. This study shows that
      immobilized microalgae using silica, a synthesized biosorbent, can be used as a
      cost-effective sorbent for Cu(II) removal from the aqueous phase.

PMID- 25953612
TI  - Benign metastasizing leiomyoma of the cervical spine 31 years after uterine
      leiomyoma resection.
AB  - We report a 74-year-old woman presenting with a leiomyoma of the cervical spine
      31 years after uterine leiomyoma resection. Benign metastasizing leiomyoma to the
      cervical spine is very rare. To the best of our knowledge, this is the fourth
      reported patient with a leiomyoma metastasizing to the cervical spine and that
      with the longest latency period for this type of tumor, 31 years. The
      pathological features were typical of leiomyoma.

PMID- 25953613
TI  - Effects of sodium phosphate and caffeine ingestion on repeated-sprint ability in
      male athletes.
AB  - OBJECTIVES: To assess the effects of sodium phosphate (SP) and caffeine
      supplementation on repeated-sprint performance. DESIGN: Randomized, double-blind,
      Latin-square design. METHODS: Eleven team-sport males participated in four
      trials: (1) SP (50mgkg(-1) of free fat-mass daily for six days) and caffeine
      (6mgkg(-1) ingested 1h before exercise); SP+C, (2) SP and placebo (for caffeine),
      (3) caffeine and placebo (for SP) and (4) placebo (for SP and caffeine). After
      loading, participants performed a simulated team-game circuit (STGC) consisting
      of 2*30min halves, with 6*20-m repeated-sprint sets performed at the start, half
      time and end of the STGC. RESULTS: There were no interaction effects between
      trials for first-sprint (FS), best-sprint (BS) or total-sprint (TS) times
      (p>0.05). However, SP resulted in the fastest times for all sprints, as supported
      by moderate to large effect sizes (ES; d=0.51-0.83) and 'likely' to 'very likely'
      chances of benefit, compared with placebo. Compared with caffeine, SP resulted in
      'possible' to 'likely' chances of benefit for FS, BS and TS for numerous sets and
      a 'possible' chance of benefit compared with SP+C for BS (set 2). Compared with
      placebo, SP+C resulted in moderate ES (d=0.50-0.62) and 'possible' to 'likely'
      benefit for numerous sprints, while caffeine resulted in a moderate ES (d=0.63;
      FS: set 3) and 'likely' chances of benefit for a number of sets. CONCLUSIONS:
      While not significant, ES and qualitative analysis results suggest that SP
      supplementation may improve repeated-sprint performance when compared with
      placebo.

PMID- 25953614
TI  - Comparison of dual protection and distal filter protection as a distal embolic
      protection method during carotid artery stenting: a single-center carotid artery
      stenting experience.
AB  - There are several protection methods used to prevent distal embolism during
      carotid artery stenting (CAS). The aim of this study was to compare the dual
      protection method (proximal balloon and distal filter protection) with the distal
      filter protection during CAS performed at a single center. Between April 2008 and
      November 2013, 78 consecutive patients with internal carotid artery stenosis were
      treated with CAS at Istukaichi Memorial Hospital. Twenty-four consecutive
      patients were treated with CAS using distal filter protection (distal filter
      protection group), and 54 consecutive patients were treated with CAS using dual
      protection with a proximal balloon and distal filter protection (dual protection
      group). We examined the hyperintensity lesions on diffusion-weighted imaging
      (DWI) and perioperative complications after CAS. All stenotic lesions were
      successfully dilated. DWI showed hyperintensity lesions among 54.2 % (13/24
      patients) in the distal filter protection group and in 27.8 % (15/54 patients) in
      the dual protection group (p = 0.024). The average number of hyperintensity
      lesions on DWI was 1.75 (range, 0 to 6) in the distal filter protection group and
      0.59 (range, 0 to 5) in the dual protection group (p = 0.0087). Postprocedural
      persistent ischemic complications occurred in 4.2 % (1/24 patients) in the distal
      filter protection group and 3.7 % (2/54 patients) in the dual protection group (p
      = 0.67). In this study, the dual protection method reduced the number of
      hyperintensity lesions seen on DWI when compared with the distal filter
      protection method when used for distal embolic protection during CAS. 

PMID- 25953615
TI  - Cats as a potential source of emerging influenza virus infections.

PMID- 25953616
TI  - The Pore Loop Domain of TRPV1 Is Required for Its Activation by the Volatile
      Anesthetics Chloroform and Isoflurane.
AB  - The environmental irritant chloroform, a naturally occurring small volatile
      organohalogen, briefly became the world's most popular volatile general
      anesthetic (VGA) before being abandoned because of its low therapeutic index.
      When chloroform comes in contact with skin or is ingested, it causes a painful
      burning sensation. The molecular basis for the pain associated with chloroform
      remains unknown. In this study, we assessed the role of transient receptor
      potential (TRP) channel family members in mediating chloroform activation and the
      molecular determinants of VGA activation of TRPV1. We identified the
      subpopulation of dorsal root ganglion (DRG) neurons that are activated by
      chloroform. Additionally, we transiently expressed wild-type or specifically
      mutated TRP channels in human embryonic kidney cells and used calcium imaging or
      whole-cell patch-clamp electrophysiology to assess the effects of chloroform or
      the VGA isoflurane on TRP channel activation. The results revealed that
      chloroform activates DRG neurons via TRPV1 activation. Furthermore, chloroform
      activates TRPV1, and it also activates TRPM8 and functions as a potent inhibitor
      of the noxious chemical receptor TRPA1. The results also indicate that residues
      in the outer pore region of TRPV1 previously thought to be required for either
      proton or heat activation of the channel are also required for activation by
      chloroform and isoflurane. In addition to identifying the molecular basis of DRG
      neuron activation by chloroform and the opposing effects chloroform has on
      different TRP channel family members, the findings of this study provide novel
      insights into the structural basis for the activation of TRPV1 by VGAs. 

PMID- 25953617
TI  - Non-coding RNA: X-chromosome inactivation unravelled.

PMID- 25953618
TI  - RNA: 3' UTR alternatives to protein localization.

PMID- 25953619
TI  - Development of methacrylate/silorane hybrid monomer system: Relationship between
      photopolymerization behavior and dynamic mechanical properties.
AB  - Resin chemistries for dental composite are evolving as noted by the introduction
      of silorane-based composites in 2007. This shift in the landscape from
      methacrylate-based composites has fueled the quest for versatile methacrylate
      silorane adhesives. The objective of this study was to evaluate the
      polymerization behavior and structure/property relationships of methacrylate
      silorane hybrid systems. Amine compound ethyl-4-(dimethylamino) benzoate (EDMAB)
      or silane compound tris(trimethylsilyl) silane (TTMSS) was selected as
      coinitiators. The mechanical properties of the copolymer were improved
      significantly at low concentrations (15, 25, or 35 wt %) of silorane when EDMAB
      was used as coinitiator. The rubbery moduli of these experimental copolymers were
      increased by up to 260%, compared with that of the control (30.8 +/- 1.9 MPa).
      Visible phase separation appeared in these formulations if the silorane
      concentrations in the formulations were 50-75 wt %. The use of TTMSS as
      coinitiator decreased the phase separation, but there was a concomitant decrease
      in mechanical properties. In the neat methacrylate formulations, the maximum
      rates of free-radical polymerization with EDMAB or TTMSS were 0.28 or 0.06 s(-1)
      , respectively. In the neat silorane resin, the maximum rates of cationic ring
      opening polymerization with EDMAB or TTMSS were 0.056 or 0.087 s(-1) ,
      respectively. The phase separation phenomenon may be attributed to differences in
      the rates of free-radical polymerization of methacrylates and cationic ring
      opening polymerization of silorane. In the hybrid systems, free-radical
      polymerization initiated with EDMAB led to higher crosslink density and better
      mechanical properties under dry/wet conditions. These beneficial effects were,
      however, associated with an increase in heterogeneity in the network structure.
      (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B:
      841-852, 2016.

PMID- 25953620
TI  - Phospholipid-based self-assembled mesophase systems for light-activated drug
      delivery.
AB  - The manipulation of the structure of phospholipid-based mesophases to induce a
      slow to fast drug release profile has potential for use in therapeutic situations
      where continuous absorption of drug is not desirable and reduce the frequency of
      injection for short acting or rapidly cleared drugs in treatments for diseases
      such as macular degeneration. This study had two aims; firstly to confirm the
      phase behaviour of 20 mol% cholesterol in 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphoethanolamine (POPE), which was previously reported to transition from
      lamellar (slow release) to bicontinuous cubic (fast release) phase with
      increasing temperature. Contrary to the literature, no bicontinuous cubic phase
      was observed but a transition to the inverse hexagonal phase occurred at all POPE
      : cholesterol ratios investigated. The second aim was to render these mesophases
      responsive to near-infrared laser (NIR) irradiation by incorporation of gold
      nanorods (GNR) incorporated into the POPE system to induce photothermal heating.
      The inclusion of 3 nM GNR in POPE systems induced reversible disruption of lipid
      packing equivalent to increasing the temperature to 55  degrees C when irradiated
      for 30 s. This study confirmed that although the previously published phase
      behavior was not correct, GNR and NIR can be used to manipulate the self
      assembled mesophases in phospholipid-based systems and highlights the potential
      for a phospholipid-based light-activated drug delivery system. 

PMID- 25953621
TI  - Integrated frameworks for assessing and managing health risks in the context of
      managed aquifer recharge with river water.
AB  - Integrated assessment and management of water resources for the supply of potable
      water is increasingly important in light of projected water scarcity in many
      parts of the world. This article develops frameworks for regional-level
      waterborne human health risk assessment of chemical and microbiological
      contamination to aid water management, incorporating economic aspects of health
      risks. Managed aquifer recharge with surface water from a river in Southern
      Finland is used as an illustrative case. With a starting point in watershed
      governance, stakeholder concerns, and value-at-risk concepts, we merge common
      methods for integrative health risk analysis of contaminants to describe risks
      and impacts dynamically and broadly. This involves structuring analyses along the
      risk chain: sources-releases-environmental transport and fate-exposures-health
      effects-socio-economic impacts-management responses. Risks attributed to
      contaminants are embedded in other risks, such as contaminants from other
      sources, and related to benefits from improved water quality. A set of models
      along this risk chain in the case is presented. Fundamental issues in the
      assessment are identified, including 1) framing of risks, scenarios, and choices;
      2) interaction of models and empirical information; 3) time dimension; 4)
      distributions of risks and benefits; and 5) uncertainties about risks and
      controls. We find that all these combine objective and subjective aspects, and
      involve value judgments and policy choices. We conclude with proposals for
      overcoming conceptual and functional divides and lock-ins to improve modeling,
      assessment, and management of complex water supply schemes, especially by
      reflective solution-oriented interdisciplinary and multi-actor deliberation.

PMID- 25953622
TI  - Primary refractory and early-relapsed Hodgkin's lymphoma: strategies for
      therapeutic targeting based on the tumour microenvironment.
AB  - Classical Hodgkin's lymphoma (cHL), a distinct disease entity with characteristic
      clinical and pathological features, accounts for approximately 10% of all
      malignant lymphomas. cHL can be considered a prototype model for how the tumour
      microenvironment influences cancer pathogenesis. Cellular components of the cHL
      microenvironment express molecules involved in cancer cell growth and survival,
      such as CD30L or CD40L. Moreover, several signal transduction pathways that are
      critical for the proliferation and survival of neoplastic Hodgkin Reed-Sternberg
      (HRS) cells, including NF-kappaB, JAK-STAT, PI3K-AkT and ERK, are deregulated in
      cHL. Although most patients can be cured with modern treatment strategies,
      approximately a quarter experience either primary or secondary
      chemorefractoriness or disease relapse, thus requiring novel treatments.
      Preclinical and clinical evidence has elucidated a complex crosstalk between
      malignant HRS cells and the reactive cells of the microenvironment, which
      suggests that novel therapeutic approaches capable of targeting HRS cells along
      with reactive cells might overcome chemorefractoriness. In the near future, these
      novel therapies will also be tested in chemosensitive patients, to reduce the
      long-term toxicity of chemo-radiotherapy.

PMID- 25953624
TI  - SDRL: a sequence-dependent protein side-chain rotamer library.
AB  - Since the introduction of the first protein side-chain rotamer library (RL)
      almost half a century ago, RLs have been components of many programs and
      algorithms in structural bioinformatics. Based on the dependence of side-chain
      dihedral angles on the local backbone, three types of RLs have been identified:
      backbone-independent, secondary-structure-dependent and backbone-dependent. In
      all previous studies, the effect of sequence specificity on side-chain
      conformational preferences was neglected. In the effort to develop a new class of
      RLs, we considered that the side-chain conformation of the central residue in
      each triplet on a protein backbone depends on the sequence of the triplet;
      therefore, we developed a sequence-dependent rotamer library (SDRL). To
      accomplish this, 400 possible triplet sequences for 18 natural amino acids as the
      central residue, which corresponds to 7200 triplet sequences in total, were
      considered. Searching the set of 11 546 selected PDB entries for the 7200 triplet
      sequences resulted in 2 364 541 instances occurring for 18 amino acids. Our
      results show that Leu and Val experience minimal impact from the adjacent
      residues in adopting side-chain conformations. Cys, Ile, Trp, His, Asp, Met, Glu,
      Gln, Arg and Lys, on the other hand, adopt their side-chain conformations mostly
      based on the adjacent residues on the backbone. The remaining residue types were
      moderately dependent on the adjacent residues. Using the new library, side-chain
      repacking algorithms can find preferred conformations of each residue more easily
      than with other backbone-independent RLs.

PMID- 25953623
TI  - Helicase-Dependent Isothermal Amplification of DNA and RNA by Using Self-Avoiding
      Molecular Recognition Systems.
AB  - Assays that detect DNA or RNA (xNA) are highly sensitive, as small amounts of xNA
      can be amplified by PCR. Unfortunately, PCR is inconvenient in low-resource
      environments, and requires equipment and power that might not be available in
      these environments. Isothermal procedures, which avoid thermal cycling, are often
      confounded by primer dimers, off-target priming, and other artifacts. Here, we
      show how a "self avoiding molecular recognition system" (SAMRS) eliminates these
      artifacts and gives clean amplicons in a helicase-dependent isothermal
      amplification (SAMRS-HDA). We also show that incorporating SAMRS into the 3'-ends
      of primers facilitates the design and screening of primers for HDA assays.
      Finally, we show that SAMRS-HDA can be twofold multiplexed, difficult to achieve
      with HDA using standard primers. Thus, SAMRS-HDA is a more versatile approach
      than standard HDA, with a broader applicability for xNA-targeted diagnostics and
      research. 

PMID- 25953625
TI  - The minor ecdysteroids from Ajuga turkestanica.
AB  - INTRODUCTION: Ajuga turkestanica is a plant used in traditional medicine for its
      high ecdysteroid content, including the presence of the particularly active
      turkesterone, which possess efficient anabolic activity. OBJECTIVES: To isolate
      and identify minor ecdysteroids present in a semi-purified plant fraction
      containing ca. 70% turkesterone. MATERIAL AND METHODS: Multi-step preparative
      HPLC (combining RP- and NP-HPLC systems) was used to purify the different
      components present in the turkesterone fraction. Isolated compounds were
      identified by high-resolution mass spectrometry and 2D-NMR. RESULTS: Fourteen
      ecdysteroids (including turkesterone and 20-hydroxyecdysone) were isolated. Seven
      of these, all bearing an 11alpha-hydroxy group, were previously unreported.
      CONCLUSION: Ajuga turkestanica ecdysteroids are characterised by the abundance of
      11alpha-hydroxylated compounds and by the simultaneous presence of 24C, 27C, 28C
      and 29C ecdysteroids. It is expected that even more ecdysteroids are to be found
      in this plant since the starting material for this study lacked the less polar
      ecdysteroids. The simultaneous presence of 20-hydroxyecdysone and turkesterone
      (its 11alpha-hydroxy analogue) as the two major ecdysteroids suggests that every
      ecdysteroid is probably present in both 11alpha-hydroxy and 11-deoxy forms.

PMID- 25953626
TI  - Partnering Around Data to Address Clinician Retention in Loan Repayment Programs:
      The Multistate/NHSC Retention Collaborative.

PMID- 25953629
TI  - Evaluation of spacer block technique using tensor device in unicompartmental knee
      arthroplasty.
AB  - INTRODUCTION: Mobile-bearing unicompartmental knee arthroplasty (UKA) was
      designed so that flexion and extension gap adjustments could achieve isometric
      function of the ligaments throughout ROM to prevent complications. However,
      achieving accurate knee balancing using a spacer block technique remains
      difficult since determination of the thickness of the spacer block is determined
      according to the feeling of the individual surgeon's hand. The objective of the
      study was to investigate flexion and extension medial unicompartmental knee gap
      kinematics in mobile-bearing UKA and to reveal the accuracy of spacer block
      measurement technique using a gap tensor device. MATERIALS AND METHODS: Mobile
      bearing UKA was performed in 40 knees of 31 subjects using generally accepted
      spacer block technique so that the extension gap was made equal to the flexion
      gap. The extension and flexion gaps of the medial knee compartment were measured
      using the tensor device with 25, 50, 75, 100, 125, and 150 N of joint distraction
      force. The interplay gap was calculated by subtracting the thickness of the
      tibial prosthesis and the thickness of the selected size of bearing from the
      measured extension and flexion gaps. Medial compartmental joint interplay gap
      differences were compared among flexion and extension gaps. RESULTS: The mean
      flexion interplay gap was 25 N: 0.5 mm, 50 N: 1.5 mm, 75 N: 2.4 mm, 100 N: 3.1
      mm, 125 N: 3.6 mm, 150 N: 4.0 mm. The mean extension interplay gap was 25 N: -0.2
      mm, 50 N: 0.81 mm, 75 N: 1.7 mm, 100 N: 2.5 mm, 125 N: 3.1 mm, 150 N: 3.5 mm. The
      measured extension gap was shown to be significantly smaller compared with the
      flexion gap at every joint distraction force (P < 0.01). CONCLUSIONS: These
      results suggest that gap measurement using a spacer block in UKA has the
      potential risk that the resulting extension gap may be smaller than the flexion
      gap. Surgeons should adjust the flexion and extension gaps with caution to
      achieve good ligament function when performing mobile-bearing UKA.

PMID- 25953628
TI  - Activation of M3 cholinoceptors attenuates vascular injury after
      ischaemia/reperfusion by inhibiting the Ca2+/calmodulin-dependent protein kinase
      II pathway.
AB  - BACKGROUND AND PURPOSE: The activation of M3 cholinoceptors (M3 receptors) by
      choline reduces cardiovascular risk, but it is unclear whether these receptors
      can regulate ischaemia/reperfusion (I/R)-induced vascular injury. Thus, the
      primary goal of the present study was to explore the effects of choline on the
      function of mesenteric arteries following I/R, with a major focus on
      Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) regulation. EXPERIMENTAL
      APPROACH: Rats were given choline (10 mg . kg(-1), i.v.) and then the superior
      mesenteric artery was occluded for 60 min (ischaemia), followed by 90 min of
      reperfusion. The M3 receptor antagonist, 4-diphenylacetoxy-N-methylpiperidine
      methiodide (4-DAMP), was injected (0.12 MUg . kg(-1), i.v.) 5 min prior to
      choline treatment. Vascular function was examined in rings of mesenteric arteries
      isolated after the reperfusion procedure. Vascular superoxide anion production,
      CaMKII and the levels of Ca(2+)-cycling proteins were also assessed. KEY RESULTS:
      Choline treatment attenuated I/R-induced vascular dysfunction, blocked elevations
      in the levels of reactive oxygen species (ROS) and decreased the up-regulated
      expression of oxidised CaMKII and phosphorylated CaMKII. In addition, choline
      reversed the abnormal expression of Ca(2+)-cycling proteins, including
      Na(+)Ca(2+) exchanger, inositol 1,4,5-trisphosphate receptor, sarcoplasmic
      reticulum Ca(2+)-ATPase and phospholamban. All of these cholinergic effects of
      choline were abolished by 4-DAMP. CONCLUSIONS AND IMPLICATIONS: Our data suggest
      that inhibition of the ROS-mediated CaMKII pathway and modulation of Ca(2+)
      cycling proteins may be novel mechanisms underlying choline-induced vascular
      protection. These results represent a significant addition to the understanding
      of the pharmacological roles of M3 receptors in the vasculature, providing a new
      therapeutic strategy for I/R-induced vascular injury.

PMID- 25953627
TI  - Adrenomedullin in lymphangiogenesis: from development to disease.
AB  - Over the past decade, we have begun to appreciate that the lymphatic vascular
      system does more than simply return plasma back into the circulatory system and,
      in fact, contributes to a wide variety of normal and disease states. For this
      reason, much research has been devoted to understanding how lymphatic vessels
      form and function, with a particular interest in which molecules contribute to
      lymphatic vessel growth and maintenance. In the following review, we focus on a
      potent lymphangiogenic factor, adrenomedullin, and its known roles in
      lymphangiogenesis, lymphatic function, and human lymphatic disease. As one of the
      first, pharmacologically tractable G protein-coupled receptor pathways
      characterized in lymphatic endothelial cells, the continued study of
      adrenomedullin effects on the lymphatic system may open new avenues for the
      modulation of lymphatic growth and function in a variety of lymphatic-related
      diseases that currently have few treatments. 

PMID- 25953630
TI  - Repair of retropatellar cartilage defects in the knee with microfracture and a
      cell-free polymer-based implant.
AB  - INTRODUCTION: To analyze magnetic resonance imaging (MRI) at 3T and the clinical
      outcome in a short-term pilot study after treatment of retropatellar cartilage
      defects with microfracturing and subsequent covering with the cell-free
      chondrotissue((r)) polyglycolic acid-hyaluronan implant. METHODS: Five
      consecutive patients after microfracturing and defect coverage with the
      chondrotissue((r)) implant immersed with autologous serum were included. After a
      mean follow-up of 21 months (range 11-31 months), defect fill and repair tissue
      quality was assessed by 3-T MRI followed by applying established MRI scoring
      systems. The patients' situation was assessed using the Knee injury and
      Osteoarthritis Outcome Score (KOOS) and a patients' satisfaction questionnaire.
      RESULTS: Magnetic resonance imaging showed good to excellent defect fill with
      complete integration. The mean MOCART score was 61 (range 50-75) points. The mean
      Henderson score was 7 (range 6-9) points. All patients showed subchondral bone
      alterations. The KOOS showed good values in all sub-categories in 4 out of 5
      patients and a mean overall score of 73 (range 40-90) points. Two patients rated
      the outcome as excellent, two as good and one as fair. All patients would have
      the procedure again and recommend it. CONCLUSIONS: In this small case series, the
      coverage of symptomatic retropatellar cartilage defects with the
      chondrotissue((r)) implant after microfracturing was safe and feasible with
      improvement of the patients' situation at short-term follow-up. LEVEL OF
      EVIDENCE: IV, case series.

PMID- 25953631
TI  - Optimization of large-scale mouse brain connectome via joint evaluation of DTI
      and neuron tracing data.
AB  - Tractography based on diffusion tensor imaging (DTI) data has been used as a tool
      by a large number of recent studies to investigate structural connectome. Despite
      its great success in offering unique 3D neuroanatomy information, DTI is an
      indirect observation with limited resolution and accuracy and its reliability is
      still unclear. Thus, it is essential to answer this fundamental question: how
      reliable is DTI tractography in constructing large-scale connectome? To answer
      this question, we employed neuron tracing data of 1772 experiments on the mouse
      brain released by the Allen Mouse Brain Connectivity Atlas (AMCA) as the ground
      truth to assess the performance of DTI tractography in inferring white matter
      fiber pathways and inter-regional connections. For the first time in the
      neuroimaging field, the performance of whole brain DTI tractography in
      constructing a large-scale connectome has been evaluated by comparison with
      tracing data. Our results suggested that only with the optimized tractography
      parameters and the appropriate scale of brain parcellation scheme, can DTI
      produce relatively reliable fiber pathways and a large-scale connectome.
      Meanwhile, a considerable amount of errors were also identified in optimized DTI
      tractography results, which we believe could be potentially alleviated by efforts
      in developing better DTI tractography approaches. In this scenario, our framework
      could serve as a reliable and quantitative test bed to identify errors in
      tractography results which will facilitate the development of such novel
      tractography algorithms and the selection of optimal parameters. 

PMID- 25953633
TI  - Societal impact and economic value of spine surgery in Brazil.

PMID- 25953632
TI  - Mechanical restriction of intracortical vessel dilation by brain tissue sculpts
      the hemodynamic response.
AB  - Understanding the spatial dynamics of dilation in the cerebral vasculature is
      essential for deciphering the vascular basis of hemodynamic signals in the brain.
      We used two-photon microscopy to image neural activity and vascular dynamics in
      the somatosensory cortex of awake behaving mice during voluntary locomotion.
      Arterial dilations within the histologically-defined forelimb/hindlimb (FL/HL)
      representation were larger than arterial dilations in the somatosensory cortex
      immediately outside the FL/HL representation, demonstrating that the vascular
      response during natural behaviors was spatially localized. Surprisingly, we found
      that locomotion drove dilations in surface vessels that were nearly three times
      the amplitude of intracortical vessel dilations. The smaller dilations of the
      intracortical arterioles were not due to saturation of dilation. Anatomical
      imaging revealed that, unlike surface vessels, intracortical vessels were tightly
      enclosed by brain tissue. A mathematical model showed that mechanical restriction
      by the brain tissue surrounding intracortical vessels could account for the
      reduced amplitude of intracortical vessel dilation relative to surface vessels.
      Thus, under normal conditions, the mechanical properties of the brain may play an
      important role in sculpting the laminar differences of hemodynamic responses. 

PMID- 25953635
TI  - Primary intraosseous squamous cell carcinoma arising from keratocystic
      odontogenic tumor.
AB  - Primary intraosseous squamous cell carcinoma (PIOSCC) is a rare lesion that
      almost exclusively occurs in the jaws. Most PIOSCCs originate from epithelial
      lining of odontogenic cysts, especially from radicular, residual, and dentigerous
      cysts. A few cases have been shown to arise from keratocystic odontogenic tumors
      (KCOTs). This is a report of a case of PIOSCC that arose from an untreated
      keratocystic odontogenic tumor within a period of less than 2 years of first
      diagnosis. Upon malignant transformation, the tumor changed from a cystic to a
      solid pattern and acquired an infiltrative growth pattern, invading and
      destroying all surrounding bone. This case underscores the importance of early
      diagnosis and treatment of KCOTs and raises the question whether some of the
      PIOSCCs classified as "solid type" could, in fact, be late-presenting PIOSCCs
      arising from KCOTs and other cystic pathologic entities within the jaws. 

PMID- 25953634
TI  - Posterior mini-incision total hip arthroplasty controls the extent of post
      operative formation of heterotopic ossification.
AB  - Heterotopic ossification (HO) is the formation of bone at extra-skeletal sites.
      Reported rates of HO after hip arthroplasty range from 8 to 90 %; however, it is
      only severe cases that cause problems clinically, such as joint stiffness. The
      effects of surgical-related controllable intra-operative risk factors for the
      formation of HO were investigated. Data examined included gender, age of patient,
      fat depth, length of operation, incision length, prosthetic fixation method, the
      use of pulsed lavage and canal brush, and component size and material. All cases
      were performed by the same surgeon using the posterior approach. A total of 510
      cases of hip arthroplasty were included, with an overall rate of HO of 10.2 %.
      Longer-lasting operations resulted in higher grades of HO (p = 0.047). Incisions
      >10 cm resulted in more widespread HO formation (p = 0.021). No further
      correlations were seen between HO formation and fat depth, blood loss,
      instrumentation, fixation methods or prosthesis material. The mini-incision
      approach is comparable to the standard approach in the aetiology of HO formation,
      and whilst the rate of HO may not be controllable, a posterior mini-incision
      approach can limit its extent. 

PMID- 25953636
TI  - Response to "Neuroepithelial structures associated with neurogenous subgemmal
      plaque of the tongue: an autopsy finding".

PMID- 25953637
TI  - The job of being a gatekeeper.

PMID- 25953638
TI  - Oral lichen planus pemphigoides: a series of four cases.
AB  - OBJECTIVE: Lichen planus pemphigoides (LPP), which is a rare autoimmune
      blistering mucocutaneous disease of the pemphigoid family of diseases, is
      characterized by the development of vesiculobullous lesions on or adjacent to the
      areas of lichen planus (LP). LPP primarily affects the skin, and oral involvement
      alone is rare. The objective of this case series was to report four new cases of
      oral LPP. STUDY DESIGN: We present four cases with clinical, histologic, and
      direct immunofluorescence (DIF) features characteristic of LPP, with three cases
      having oral involvement only. RESULTS: The four patients (including two males)
      were aged 49, 50, 51, and 61 years; only one patient had skin lesions. All
      patients had typical reticular, erythematous, or ulcerative oral LP involving the
      gingiva and the buccal mucosa. Mucosal biopsies showed features consistent with
      LP, mucous membrane pemphigoid (MMP), or a combination of both, and DIF studies
      in all 4 cases showed linear deposition of immunoglobulin G (IgG) and C3 at the
      interface. CONCLUSIONS: Correlation of clinical findings, routine histopathology,
      and DIF studies is essential for the diagnosis.

PMID- 25953639
TI  - Micro-ribonucleic acid 143 (MiR-143) inhibits oral squamous cell carcinoma (OSCC)
      cell migration and invasion by downregulation of phospho-c-Met through targeting
      CD44 v3.
AB  - OBJECTIVE: The aim of this study was to investigate the roles and mechanisms of
      Micro-ribonucleic acid 143 (miR-143) in oral squamous cell carcinoma cells. STUDY
      DESIGN: Following the detection of miR-143 expression, cell proliferation,
      migration, and invasion assays and Western blot analysis were conducted in the
      oral squamous cell carcinoma (OSCC) cell lines. RESULTS: We found that the
      expression of miR-143 was significantly decreased in the OSCC cell lines (SCC-4,
      Tca-8113, CAL-27) and tumor tissues. Meanwhile, miR-143 was significantly
      correlated with the migration and invasion in OSCC cell lines. Further
      investigation revealed that the expression level of miR-143 was opposite to that
      of its potential target gene-CD44 v3 and was also related to phospho-c-Met
      activation. CONCLUSIONS: miR-143 could exert significantly suppressive effects on
      the ability of migration and invasion in OSCC cell lines, and the mechanism of
      this might be related to the activity of phospho-c-met though the CD44 v3/HGF
      signal. miR-143 could thus provide new applications for the treatment of OSCC.

PMID- 25953640
TI  - World Workshop on Oral Medicine VI: a systematic review of the treatment of
      mucous membrane pemphigoid.
AB  - OBJECTIVE: To determine the efficacy and safety of interventions for mucous
      membrane pemphigoid (MMP). STUDY DESIGN: We conducted a systematic review from
      2003 to 2013 according to the Cochrane Collaboration methodology. Randomized
      controlled trials (RCTs) or controlled clinical trials and observational studies
      were included, with diagnosis confirmed by clinical, histopathologic, and
      immunofluorescence criteria. The primary outcome was lesion remission or healing;
      several relevant secondary outcomes were also included. RESULTS: In the final
      analysis, 1 RCT and 32 observational studies were included. The one included RCT
      with a high risk of bias in multiple domains found limited evidence that
      pentoxifylline, combined with corticosteroid and cyclophosphamide, was more
      effective than standard therapy (corticosteroid + cyclophosphamide alone) for
      ocular MMP. We summarize here the outcomes from 32 observational studies
      examining 242 patients across 19 unique treatments. Interventions that show
      promise include rituximab and intravenous immunoglobulin. CONCLUSIONS: This
      systematic review is the most recent since 2003-2009. There is still lack of high
      quality research providing evidence-based MMP treatments.

PMID- 25953641
TI  - Psychoeducation for siblings of people with severe mental illness.
AB  - BACKGROUND: Many people with severe mental illness (SMI) have siblings. Siblings
      are often both natural agents to promote service users' recovery and vulnerable
      to mental ill health due to the negative impact of psychosis within the family.
      Despite a wealth of research evidence supporting the effectiveness of
      psychoeducation for service users with SMI and their family members, in reducing
      relapse and promoting compliance with treatment, siblings remain relatively
      invisible in clinical service settings as well as in research studies. If
      psychoeducational interventions target siblings and improve siblings' knowledge,
      coping with caring and overall wellbeing, they could potentially provide a cost
      effective option for supporting siblings with resulting benefits for service
      users' outcomes. OBJECTIVES: To assess the effectiveness of psychoeducation
      compared with usual care or any other intervention in promoting wellbeing and
      reducing distress of siblings of people affected by SMI.The secondary objective
      was, if possible, to determine which type of psychoeducation is most effective.
      SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register and
      screened the reference lists of relevant reports and reviews (12th November
      2013). We contacted trial authors for unpublished and specific data on siblings'
      outcomes. SELECTION CRITERIA: All relevant randomised controlled trials focusing
      on psychoeducational interventions targeting siblings of all ages (on their own
      or amongst other family members including service users) of individuals with SMI,
      using any means and formats of delivery, i.e. individual (family), groups,
      computer-based. DATA COLLECTION AND ANALYSIS: Two review authors independently
      screened the abstracts and extracted data and two other authors independently
      checked the screening and extraction process. We contacted authors of trials to
      ascertain siblings' participation in the trials and seek sibling-specific data in
      those studies where siblings' data were grouped together with other participants'
      (most commonly other family members'/carers') outcomes. We calculated the risk
      difference (RD), its 95% confidence interval (CI) on an intention-to-treat basis.
      We presented continuous data using the mean difference statistic (MD) and 95%
      CIs. We assessed risk of bias for the included study and rated quality of
      evidence using Grading of Recommendations Assessment, Development and Evaluation
      (GRADE). MAIN RESULTS: We found 14 studies that included siblings amongst other
      family members in receipt of psychoeducational interventions. However, we were
      only able to include one small trial with relevant and available data (n = 9
      siblings out of n = 84 family member/carer-participants) comparing
      psychoeducational intervention with standard care in a community care setting,
      over a duration of 21 months. There was insufficient evidence to determine the
      effects of psychoeducational interventions compared with standard care on
      'siblings' quality of life' (n = 9, MD score 3.80 95% CI -0.26 to 7.86, low
      quality of evidence), coping with (family) burden (n = 9, MD -8.80 95% CI -15.22
      to -2.34, low quality of evidence). No sibling left the study early by one year
      (n = 9, RD 0.00 CI -0.34 to 0.34, low quality of evidence). Low quality and
      insufficient evidence meant we were unable to determine the effects of
      psychoeducational interventions compared with standard care on service users'
      global mental state (n = 9, MD -0.60 CI -3.54 to 2.38, low quality of evidence),
      their frequency of re-hospitalisation (n = 9, MD -0.70 CI -2.46 to 1.06, low
      quality of evidence) or duration of inpatient stay (n = 9, MD -2.60 CI -6.34 to
      1.14, low quality of evidence), whether their siblings received psychoeducation
      or not. No study data were available to address the other primary outcomes:
      'siblings' psychosocial wellbeing', 'siblings' distress' and adverse effects.
      AUTHORS' CONCLUSIONS: Most studies evaluating psychoeducational interventions
      recruited siblings along with other family members. However, the proportion of
      siblings in these studies was low and outcomes for siblings were not reported
      independently from those of other types of family members. Indeed, only data from
      one study with nine siblings were available for the review. The limited study
      data we obtained provides no clear good quality evidence to indicate
      psychoeducation is beneficial for siblings' wellbeing or for clinical outcomes of
      people affected by SMI. More randomised studies are justified and needed to
      understand the role of psychoeducation in addressing siblings' needs for
      information and support.

PMID- 25953642
TI  - What a pain.

PMID- 25953643
TI  - Practitioners should embrace, not ignore, health apps.

PMID- 25953644
TI  - Substance use and treatment of substance use disorders in a community sample of
      transgender adults.
AB  - BACKGROUND: Transgender people have elevated substance use prevalence compared
      with the U.S. general population, however no studies have comprehensively
      examined the relationship of psychosocial risk factors to substance use and
      substance use disorder (SUD) treatment among both male-to-female (MTF) and female
      to-male (FTM) transgender adults. METHODS: Secondary data analysis of a 2013
      community-based survey of transgender adults in Massachusetts (N=452) was
      conducted. Adjusted multivariable logistic regression models were fit to examine
      the relationship of four risk factor domains with SUD treatment history and
      recent substance use: (1) demographics; (2) gender-related characteristics; (3)
      mental health; (4) socio-structural factors. Adjusted Odds Ratios (aOR) and 95%
      Confidence Intervals (95% CI) were estimated. RESULTS: Ten percent of the sample
      reported lifetime SUD treatment. Factors associated with significant increase in
      odds of lifetime SUD treatment alongside recent substance use (all p<0.05) were:
      (1) older age (aOR=1.02; 95% CI=1.01-1.04), higher educational attainment
      (aOR=3.59; 95% CI=2.35-5.50), low income (aOR=0.58; 95% CI=0.39-0.86); (2) MTF
      identity (aOR=3.03; 95% CI=1.95-4.67), gender-affirming medical care (aOR=1.99;
      95% CI=1.32-3.00); (3) intimate partner violence (aOR=1.68; 95% CI=1.13-2.49),
      posttraumatic stress disorder (aOR=2.56; 95% CI=1.69-3.88), depression (aOR=2.30;
      95% CI=1.58-3.35), mental health treatment (aOR=1.65; 95% CI=1.11-2.45); (4)
      discrimination (aOR=1.90; 95% CI=1.22-2.95), unstable housing (aOR=1.80; 95%
      CI=1.21-2.67), and sex work (aOR=2.48; 95% CI=1.24-4.95). CONCLUSIONS: Substance
      use and SUD treatment among transgender adults are associated with demographic,
      gender-related, mental health, and socio-structural risk factors. Studies are
      warranted that identify SUD treatment barriers, and integrate SUD treatment with
      psychosocial and structural interventions for a diverse spectrum of transgender
      adults.

PMID- 25953645
TI  - Elevated Plasma Levels of MMP-12 Are Associated With Atherosclerotic Burden and
      Symptomatic Cardiovascular Disease in Subjects With Type 2 Diabetes.
AB  - OBJECTIVE: Matrix metalloproteinases (MMPs) degrade extracellular matrix proteins
      and play important roles in development and tissue repair. They have also been
      shown to have both protective and pathogenic effects in atherosclerosis, and
      experimental studies have suggested that MMP-12 contributes to plaque growth and
      destabilization. The objective of this study was to investigate the associations
      between circulating MMPs, atherosclerosis burden, and incidence of cardiovascular
      disease with a particular focus on type 2 diabetes mellitus. APPROACH AND
      RESULTS: Plasma levels of MMP-1, -3, -7, -10, and -12 were analyzed by the
      Proximity Extension Assay technology in 1500 subjects participating in the SUMMIT
      (surrogate markers for micro- and macrovascular hard end points for innovative
      diabetes tools) study, 384 incident coronary cases, and 409 matched controls in
      the Malmo Diet and Cancer study and in 205 carotid endarterectomy patients.
      Plasma MMP-7 and -12 were higher in subjects with type 2 diabetes mellitus,
      increased with age and impaired renal function, and was independently associated
      with prevalent cardiovascular disease, atherosclerotic burden (as assessed by
      carotid intima-media thickness and ankle-brachial pressure index), arterial
      stiffness, and plaque inflammation. Baseline MMP-7 and -12 levels were increased
      in Malmo Diet and Cancer subjects who had a coronary event during follow-up.
      CONCLUSIONS: The plasma level of MMP-7 and -12 are elevated in type 2 diabetes
      mellitus, associated with more severe atherosclerosis and an increased incidence
      of coronary events. These observations provide clinical support to previous
      experimental studies, demonstrating a role for these MMPs in plaque development,
      and suggest that they are potential biomarkers of atherosclerosis burden and
      cardiovascular disease risk.

PMID- 25953646
TI  - Heritability of Biomarkers of Oxidized Lipoproteins: Twin Pair Study.
AB  - OBJECTIVE: To determine whether biomarkers of oxidized lipoproteins are
      genetically determined. Lipoprotein(a) (Lp[a]) is a heritable risk factor and
      carrier of oxidized phospholipids (OxPL). APPROACH AND RESULTS: We measured
      oxidized phospholipids on apolipoprotein B-containing lipoproteins (OxPL-apoB),
      Lp(a), IgG, and IgM autoantibodies to malondialdehyde-modified low-density
      lipoprotein, copper oxidized low-density lipoprotein, and apoB-immune complexes
      in 386 monozygotic and dizygotic twins to estimate trait heritability (h(2)) and
      determine specific genetic effects among traits. A genome-wide linkage study
      followed by genetic association was performed. The h(2) (scale: 0-1) for Lp(a)
      was 0.91+/-0.01 and for OxPL-apoB 0.87+/-0.02, which were higher than
      physiological, inflammatory, or lipid traits. h(2) of IgM malondialdehyde
      modified low-density lipoprotein, copper oxidized low-density lipoprotein, and
      apoB-immune complexes were 0.69+/-0.04, 0.67+/-0.05, and 0.80+/-0.03,
      respectively, and for IgG malondialdehyde-modified low-density lipoprotein,
      copper oxidized low-density lipoprotein, and apoB-immune complexes 0.62+/-0.05,
      0.52+/-0.06, and 0.53+/-0.06, respectively. There was an inverse correlation
      between the major apo(a) isoform and OxPL-apoB (R=-0.49; P<0.001) and Lp(a) (R=
      0.48; P<0.001) and OxPL-apoB was modestly correlated with Lp(a) (rho=0.57;
      P<0.0001). The correlation in major apo(a) isoform size was concordant (R=1.0;
      P<0.001) among monozygotic twins but not dizygotic twins (R=0.40; P=0.055). Lp(a)
      and OxPL-apoB shared genetic codetermination (genetic covariance, rhoG=0.774+/
      0.032; P=1.09*10(-38)), although not environmental determination (environmental
      covariance, rhoE=0.081+/-0.15; P=0.15). In contrast, Lp(a) shared environmental
      but not genetic codetermination with autoantibodies to malondialdehyde-modified
      low-density lipoprotein and copper oxidized low-density lipoprotein, and apoB
      immune complexes. Sib-pair genetic linkage of the Lp(a) trait revealed that
      single nucleotide polymorphism rs10455872 was significantly associated with OxPL
      apoB after adjusting for Lp(a). CONCLUSIONS: OxPL-apoB and other biomarkers of
      oxidized lipoproteins are highly heritable cardiovascular risk factors that
      suggest novel genetic origins of atherothrombosis.

PMID- 25953648
TI  - Interferons as Essential Modulators of Atherosclerosis.
AB  - Interferons (IFNs) are key regulators of both innate and adaptive immune
      responses. The family of IFN cytokines can be divided into 3 main subtypes of
      which type I and type II IFNs are most well-defined. IFNs are known to be
      important mediators in atherosclerosis. Evidence from both in vitro and in vivo
      studies shows that the IFNs are generally proatherosclerotic. However, their role
      in atherosclerosis is complex, with distinct roles for these cytokines throughout
      different stages of the disease. In this review, we will discuss the current
      knowledge on the role of type I and type II IFNs in atherosclerosis development,
      specifically focusing on their role in endothelial activation, cell recruitment,
      foam cell formation, and regulation of apoptosis. Furthermore, we will discuss
      whether IFNs could be considered as new molecular targets for therapeutic
      intervention in atherosclerosis. 

PMID- 25953647
TI  - Flow-Dependent Epigenetic DNA Methylation in Endothelial Gene Expression and
      Atherosclerosis.
AB  - Epigenetic mechanisms that regulate endothelial cell gene expression are now
      emerging. DNA methylation is the most stable epigenetic mark that confers
      persisting changes in gene expression. Not only is DNA methylation important in
      rendering cell identity by regulating cell type-specific gene expression
      throughout differentiation, but it is becoming clear that DNA methylation also
      plays a key role in maintaining endothelial cell homeostasis and in vascular
      disease development. Disturbed blood flow causes atherosclerosis, whereas stable
      flow protects against it by differentially regulating gene expression in
      endothelial cells. Recently, we and others have shown that flow-dependent gene
      expression and atherosclerosis development are regulated by mechanisms dependent
      on DNA methyltransferases (1 and 3A). Disturbed blood flow upregulates DNA
      methyltransferase expression both in vitro and in vivo, which leads to genome
      wide DNA methylation alterations and global gene expression changes in a DNA
      methyltransferase-dependent manner. These studies revealed several
      mechanosensitive genes, such as HoxA5, Klf3, and Klf4, whose promoters were
      hypermethylated by disturbed blood flow, but rescued by DNA methyltransferases
      inhibitors such as 5Aza-2-deoxycytidine. These findings provide new insight into
      the mechanism by which flow controls epigenomic DNA methylation patterns, which
      in turn alters endothelial gene expression, regulates vascular biology, and
      modulates atherosclerosis development. 

PMID- 25953649
TI  - Attentional orienting to own and others' hands.
AB  - High-density electroencephalographic recordings were used to investigate the
      level of analysis at which attentional expectations modulate the processing of
      specific stimuli from the same perceptual category but differentiated in terms of
      a particular non-perceptual feature: body ownership. We used a task in which
      colour cues predicted whether a picture of a hand stimulus belonged to the
      participant or to somebody else. Participants were instructed to respond whether
      the target was a left or a right hand. Results revealed that the ERP pattern
      depended on stimulus ownership and attention orienting, which influenced the
      visual processing of own and someone else's hands differentially. Larger
      amplitude for others' than for own hands was shown at the N1 deflection (at the
      right hemisphere). Attentional effects were found at the P2 and P3 potentials.
      The P2 reflected an interaction between stimulus ownership and attentional
      orienting, due to a larger validity effect for others' hands. At the P3 level,
      the data showed a significant validity effect only for self-hand stimuli. In sum,
      our results suggest that (1) differences as a function of stimulus ownership can
      be detected at early levels of stimulus processing; (2) endogenous attention can
      be directed to exemplars within the same category, hand stimuli in this case; (3)
      the effects of attention are modulated by ownership. 

PMID- 25953650
TI  - Auditory white noise reduces postural fluctuations even in the absence of vision.
AB  - The contributions of somatosensory, vestibular, and visual feedback to balance
      control are well documented, but the influence of auditory information,
      especially acoustic noise, on balance is less clear. Because somatosensory noise
      has been shown to reduce postural sway, we hypothesized that noise from the
      auditory modality might have a similar effect. Given that the nervous system uses
      noise to optimize signal transfer, adding mechanical or auditory noise should
      lead to increased feedback about sensory frames of reference used in balance
      control. In the present experiment, postural sway was analyzed in healthy young
      adults where they were presented with continuous white noise, in the presence and
      absence of visual information. Our results show reduced postural sway variability
      (as indexed by the body's center of pressure) in the presence of auditory noise,
      even when visual information was not present. Nonlinear time series analysis
      revealed that auditory noise has an additive effect, independent of vision, on
      postural stability. Further analysis revealed that auditory noise reduced
      postural sway variability in both low- and high-frequency regimes (> or <0.3 Hz)
      of sway, suggesting that both spontaneous and feedback-driven aspects of postural
      fluctuations were influenced by acoustic noise. Our results support the idea that
      auditory white noise reduces postural sway, suggesting that auditory noise might
      be used for therapeutic and rehabilitation purposes in older individuals and
      those with balance disorders. 

PMID- 25953651
TI  - Orchestrating emotion and action in an evolutionary framework: Comment on "The
      quartet theory of human emotions: An integrative and neurofunctional model" by S.
      Koelsch et al.

PMID- 25953652
TI  - How to dissect complex traits and how to choose suitable mapping resources for
      system genetics?: Comment on "Mapping complex traits as a dynamic system" by L.
      Sun and R. Wu.

PMID- 25953653
TI  - Low coverage of central point vaccination against dog rabies in Bamako, Mali.
AB  - Canine rabies remains an important public-health problem in Africa. Dog mass
      vaccination is the recommended method for rabies control and elimination. We
      report on the first small-scale mass dog vaccination campaign trial in Bamako,
      Mali. Our objective was to estimate coverage of the vaccination campaign and to
      quantify determinants of intervention effectiveness. In September 2013, a central
      point vaccination campaign--free of cost for dog owners--was carried out in 17
      posts on three consecutive days within Bamako's Commune 1. Vaccination coverage
      and the proportion of ownerless dogs were estimated by combining mark-recapture
      household and transect surveys using Bayesian modeling. The estimated vaccination
      coverage was 17.6% (95% Credibility Interval, CI: 14.4-22.1%) which is far below
      the World Health Organization (WHO) recommended vaccination coverage of 70%. The
      Bayesian estimate for the owned dog population of Commune 1 was 3459 dogs (95%
      CI: 2786-4131) and the proportion of ownerless dogs was about 8%. The low
      coverage observed is primarily attributed to low participation by dog owners. Dog
      owners reported several reasons for not bringing their dogs to the vaccination
      posts. The most frequently reported reasons for non-attendance were lack of
      information (25%) and the inability to handle the dog (16%). For 37% of
      respondents, no clear reason was given for non-vaccination. Despite low coverage,
      the vaccination campaign in Bamako was relatively easy to implement, both in
      terms of logistics and organization. Almost half of the participating dog owners
      brought their pets on the first day of the campaign. Participatory stakeholder
      processes involving communities and local authorities are needed to identify
      effective communication channels and locally adapted vaccination strategies,
      which could include both central-point and door-to-door vaccination.

PMID- 25953654
TI  - Significant Association Between CAV1 Variant rs3807989 on 7p31 and Atrial
      Fibrillation in a Chinese Han Population.
AB  - BACKGROUND: Recent genome-wide association studies (GWAS) in European ancestry
      populations revealed several genomic loci for atrial fibrillation (AF). We
      previously replicated the 4q25 locus (PITX2) and 16q22 locus (ZFHX3) in the
      Chinese population, but not the KCNN3 locus on 1q21. With single-nucleotide
      polymorphism rs3807989 in CAV1 encoding caveolin-1, however, controversial
      results were reported in 2 Chinese replication studies. METHODS AND RESULTS: Six
      remaining AF genetic loci from GWAS, including rs3807989/CAV1, rs593479/PRRX1,
      rs6479562/C9orf3, rs10824026/SYNPO2L, rs1152591/SYNE2, and rs7164883/HCN4, were
      analyzed in a Chinese Han population with 941 cases and 562 controls. Only
      rs3807989 showed significant association with AF (Padj=4.77*10(-5)), and the
      finding was replicated in 2 other independent populations with 709 cases and 2175
      controls, 463 cases and 644 controls, and the combined population with a total of
      2113 cases and 3381 controls (Padj=2.20*10(-9); odds ratio [OR]=1.34 for major
      allele G). Meta-analysis, together with data from previous reports in Chinese and
      Japanese populations, also showed a significant association between rs3807989 and
      AF (P=3.40*10(-4); OR=1.24 for allele G). We also found that rs3807989 showed a
      significant association with lone AF in 3 independent populations and in the
      combined population (Padj=3.85*10(-8); OR=1.43 for major allele G). CONCLUSIONS:
      The data in this study revealed a significant association between rs3807989 and
      AF in the Chinese Han population. Together with the findings that caveolin-1
      interacts with potassium channels Kir2.1, KCNH2, and HCN4 and sodium channels
      Nav1.5 and Nav1.8, CAV1 becomes a strong candidate susceptibility gene for AF
      across different ethnic populations. This study is the first to show a
      significant association between rs3807989 and lone AF.

PMID- 25953655
TI  - Systolic Blood Pressure Response During Exercise Stress Testing: The Henry Ford
      ExercIse Testing (FIT) Project.
AB  - BACKGROUND: The prognostic significance of modest elevations in exercise systolic
      blood pressure response has not been extensively examined. METHODS AND RESULTS:
      We examined the association between systolic blood pressure response and all
      cause death and incident myocardial infarction (MI) in 44 089 (mean age 53+/-13
      years, 45% female, 26% black) patients who underwent exercise treadmill stress
      testing from the Henry Ford ExercIse Testing (FIT) Project (1991-2010). Exercise
      systolic blood pressure response was examined as a categorical variable (>20 mm
      Hg: referent; 1 to 20 mm Hg, and <=0 mm Hg) and per 1 SD decrease. Cox regression
      was used to compute hazard ratios (HR) and 95% CI for the association between
      systolic blood pressure response and all-cause death and incident MI. Over a
      median follow-up of 10 years, a total of 4782 (11%) deaths occurred and over 5.2
      years, a total of 1188 (2.7%) MIs occurred. In a Cox regression analysis adjusted
      for demographics, physical fitness, and cardiovascular risk factors, an increased
      risk of death was observed with decreasing systolic blood pressure response (>20
      mm Hg: HR=1.0, referent; 1 to 20 mm Hg: HR=1.13, 95% CI=1.05, 1.22; <=0 mm Hg:
      HR=1.21, 95% CI=1.09, 1.34). A trend for increased MI risk was observed (>20 mm
      Hg: HR=1.0, referent; 1 to 20 mm Hg: HR=1.09, 95% CI=0.93, 1.27; <=0 mm Hg:
      HR=1.19, 95% CI=0.95, 1.50). Decreases in systolic blood pressure response per 1
      SD were associated with an increased risk for all-cause death (HR=1.08, 95%
      CI=1.05, 1.11) and incident MI (HR=1.09, 95% CI=1.03, 1.16). CONCLUSIONS: Our
      results suggest that modest increases in exercise systolic blood pressure
      response are associated with adverse outcomes.

PMID- 25953656
TI  - Accuracy of preoperative CT T staging of renal cell carcinoma: which features
      predict advanced stage?
AB  - AIMS: To characterise CT findings in renal cell carcinoma (RCC), and establish
      which features are associated with higher clinical T stage disease, and to
      evaluate patterns of discrepancy between radiological and pathological staging of
      RCC. MATERIALS AND METHODS: Preoperative CT studies of 92 patients with 94
      pathologically proven RCCs were retrospectively reviewed. CT stage was compared
      with pathological stage using the American Joint Committee on Cancer (AJCC),
      7(th) edition (2010). The presence or absence of tumour necrosis, perinephric fat
      standing, thickening of Gerota's fascia, collateral vessels were noted, and
      correlated with pT stage. The sensitivity, specificity, and positive (PPV) and
      negative predictive values (NPV) for predicting pT stage >=pT3a were derived
      separately for different predictors using cross-tabulations. RESULTS: Twenty-four
      lesions were pathological stage T1a, 21 were T1b, seven were T2a, 25 were T3a, 11
      were T3b, four were T3c, and two were T4. There were no stage T2b. Sixty-three
      (67%) patients had necrosis, 27 (29%) thickening of Gerota's fascia (1 T1a), 25
      had collateral vessels (0 T1a), 28 (30%) had fat stranding of <2 mm, 20 (21%) of
      2-5mm and one (1%) of >5 mm. For pT stage >=pT3a, the presence of perinephric fat
      stranding had a sensitivity, specificity, PPV and NPV of 74%, 65%, 63%, and 76%,
      respectively. Presence of tumour necrosis had a sensitivity, specificity, PPV,
      and NPV of 81%, 44%, 54%, and 72%, respectively. Thickening of Gerota's fascia
      had a sensitivity, specificity, PPV, and NPV of 52%, 90%, 81% and 70%,
      respectively; and enlarged collateral vessels had a sensitivity, specificity,
      PPV, and NPV value of 52%, 94%, 88%, and 71% respectively. CONCLUSION: The
      presence of perinephric stranding and tumour necrosis were not reliable signs for
      pT stage >T3a. Thickening of Gerota's fascia and the presence of collateral
      vessels in the peri- or paranephric fat had 90% and 94% specificity, with 82% and
      88% PPV, respectively, for the presence of tumour stage for pT stage >T3a. These
      are considered reliable signs of locally advanced renal cancer.

PMID- 25953657
TI  - Long-term sequelae treatment of peripheral facial paralysis with botulinum toxin
      type A: Repartition and kinetics of doses used.
AB  - STUDY OBJECTIVES: Botulinum toxin is a key therapeutic tool in the comprehensive
      treatment of peripheral facial paralysis. It fights spasms, synkinesis and
      overactivity of the different skin muscles responsible of facial expressions.
      Even though injection techniques as well as target muscles have been well
      identified, doses used remain quite imprecise and often not detailed muscle by
      muscle, further more dosage progression has not been monitored over time. Our
      retrospective study is the first one to refine the repartition of botulinum toxin
      doses on each of the relevant skin muscles and assess dosage kinetics. PATIENTS
      AND METHODS: Thirty patients were included since 2008 with a mean follow-up of
      2.3years. Each patient had at least 3 injections, with a delay of 4 to 6months
      between each injection. RESULTS: Mean doses are indicated for each muscle
      injected on the paralyzed and healthy sides. Dose kinetics suggests an initial
      dosage increase after the first injection followed by a decrease over time. No
      treatment resistance was observed. CONCLUSION: Our study represents a didactic
      help in using botulinum toxin for sequelae of peripheral facial paralysis by
      providing more details on the effective mean doses for each muscle and their
      progression over time.

PMID- 25953658
TI  - Exuberant cortical thymocyte proliferation mimicking T-lymphoblastic lymphoma
      within recurrent large inguinal lymph node masses of localized Castleman disease.
AB  - We report a 13-year-old adolescent girl, the youngest thus far, with "an indolent
      T-lymphoblastic" proliferation (~10%) that uniquely presented within recurrent,
      large inguinal lymph node masses in a predominating (90%) background of Castleman
      disease. These nodal masses were resected thrice; the patient is well 5 years
      after diagnosis without further treatment. Histologically, the features of
      Castleman disease, hyaline vascular type, were present. Importantly, the
      interfollicular T-lymphoblastic component occurred as multiple clusters and
      islands of variable shapes and sizes composed of small "lymphoblasts"
      indistinguishable from normal cortical thymocytes but without thymic epithelial
      cells. Immunohistochemically, these lymphoblasts were consistent with the
      intermediate stage of T-cell differentiation (TdT(+)CD34(
      )CD99(+)CD1a(+)CD2(+)CD3(+)CD4(+)CD8(+)CD5(+)CD7(+)CD10(+) [subset]), with 80% Ki
      67. Molecularly, the T cells were nonclonal. Our case provides evidence for the
      benign nature of this highly unusual and poorly understood entity; because the
      current terminology can be readily misinterpreted as an indolent lymphoblastic
      lymphoma, we suggest a new term accurately reflecting this entity. 

PMID- 25953660
TI  - International Conference on Emerging Trends in Biotechnology. Preface.

PMID- 25953659
TI  - Systematic item selection process applied to developing item pools for assessing
      multiple mental health problems.
AB  - OBJECTIVES: Given high rates of comorbidity among mental disorders, better
      methods to rapidly screen across multiple mental disorders are needed. Building
      on existing Patient Reported Outcomes Measurement Information System (PROMIS)
      item banks, the present study aimed to select items to assess panic disorder,
      social anxiety disorder, obsessive-compulsive disorder, posttraumatic stress
      disorder, adult attention-deficit hyperactivity disorder, substance use disorder,
      suicidal thoughts and behaviors, and psychosis. STUDY DESIGN AND SETTING: A four
      stage process to select items involved systematic literature searches, item
      refinement and standardization, obtaining feedback from consumers and experts,
      and reduction of item pools in preparation for calibration in a population-based
      sample. RESULTS: From 6,900 items collected across the eight mental health
      conditions, 2,002 were standardized and rated by small groups of consumers and
      experts. Expert ratings of item relevance tended to correlate moderately with
      consumer ratings, with variation across conditions. An algorithm was used to
      generate final item pools ranging from 45 to 75 items. CONCLUSION: The study
      successfully applied a systematic process to select items for assessing a range
      of mental disorders. This process for item selection may be applied to additional
      mental and physical health conditions. The calibration of the present item pools
      into final item banks will enable the development of flexible measures to assess
      risk of mental health problems, although more effectively accounting for
      comorbidity.

PMID- 25953661
TI  - Decreased expression of follicular dendritic cell-secreted protein correlates
      with increased immunoglobulin A production in the tonsils of individuals with
      immunoglobulin A nephropathy.
AB  - Immunoglobulin A nephropathy (IgAN) is characterized by a qualitative abnormality
      of IgA in the circulation and IgA deposition in the renal mesangium. Recent
      research has indicated that pathogenic IgA may originate from affected tonsils.
      Follicular dendritic cell-secreted protein (FDC-SP), a small novel secretory
      protein that may regulate the induction of B-cell responses, has been suggested
      to control IgA production. Given this background, this study investigated the
      expression of FDC-SP and its correlation with IgA production in the tonsils of
      IgAN patients. Immunohistochemistry and reverse transcription-polymerase chain
      reaction were used to compare the expression of FDC-SP in the tonsils of IgAN
      patients with tonsillitis and of non-IgAN patients with chronic tonsillitis. The
      location of FDC-SP in tonsillar tissue was confirmed by double
      immunofluorescence. We found that FDC-SP expression significantly decreased and
      was correlated negatively with enhanced IgA production in the tonsils of IgAN
      patients. FDC-SP secreted by follicular dendritic cells may act on germinal
      center B cells and participate in the modulation of IgA generation in the
      tonsils. Our study demonstrated that FDC-SP may be involved in IgA production in
      the tonsils of IgAN patients, making this protein an attractive candidate
      immunomodulator, and highlighting a promising strategy for therapeutic
      intervention in IgAN. 

PMID- 25953662
TI  - Diagnostic value of tumor antigens in malignant pleural effusion: a meta
      analysis.
AB  - The diagnostic value of tumor markers, carcinoembryonic antigen (CEA), cancer
      antigen (CA) 15-3, CA 19-9, CA 125, cytokeratin fragment (CYFRA), and neuron
      specific enolase (NSE) in pleural fluid to differentiate between benign and
      malignant pleural effusion (MPE) has not yet been clearly established. A review
      of English language studies using human subjects was performed. Sensitivity and
      specificity values of the chosen tumor markers were pooled using a random effects
      model to generate hierarchical summary receiver operator curves to determine the
      diagnostic performance of each tumor marker. A total of 49 studies were included
      in the final analysis. Pooled sensitivity and specificity values for chosen tumor
      markers for diagnosing MPE are as follows: CEA, 0.549 and 0.962; CA 15-3, 0.507
      and 0.983; CA 19-9, 0.376 and 0.980; CA 125, 0.575 and 0.928; CYFRA, 0.625 and
      0.932; NSE, 0.613 and 0.884. The use of individual tumor markers in diagnosing
      MPE has many benefits (cost, invasiveness, and so forth). Although these tumor
      markers exhibit high specificity, the low sensitivity of each marker limits the
      diagnostic value. We conclude that tumor markers used individually are of
      insufficient diagnostic accuracy for clinical use. Tumor markers used in various
      combinations or from serum may have some potential worth further investigation. 

PMID- 25953663
TI  - Frequent nightmares are associated with blunted cortisol awakening response in
      women.
AB  - Nightmares are relatively common sleep complaints that seem to be associated with
      affective distress. To date, few attempts have been made to link nightmares to
      the biological markers of the stress response, and the HPA response in
      particular. The present study examined the relationship between frequent
      nightmares and the cortisol awakening response (CAR) in a cross-sectional study
      of working women (N=188). Analysis revealed that those who reported frequent
      nightmares (N=13) showed a blunted CAR on a working day, compared to those who
      did not report nightmares. This result was independent of psychiatric symptoms,
      demographic variables, and lifestyle. Our preliminary findings suggest that
      decreased HPA reactivity might be a trait-like feature of women with frequent
      nightmares. 

PMID- 25953664
TI  - Abnormal instability, excess density, and aberrant morphology of dendritic spines
      in prenatally testosterone-exposed mice.
AB  - Fetal brain development is programmed by the maternal intrauterine environment,
      and disturbance of the in utero environment leads to persisting deficits in brain
      functions of the offspring. Testosterone is an intrauterine environmental factor,
      and plays significant roles in fetal development. From human and animal model
      studies, it has been suggested that increased intrauterine testosterone
      concentration triggers subsequent autistic-like behavior of the offspring;
      however, the effects of maternal excess testosterone on synaptic development of
      the offspring remain unknown. In the present study, we employed prenatally
      testosterone-exposed mice, and by using in vivo two-photon imaging, we analyzed
      the dynamics, density, and morphology of the dendritic spine, an excitatory
      postsynaptic structure. We found that the offspring from testosterone-treated
      dams showed abnormal synaptic instability persisting into young adulthood,
      whereas dendritic spines in control mice became stabilized with normal synaptic
      maturation. In prenatally testosterone-exposed mice, the density of dendritic
      spines was excessively increased, and their morphology was abnormal. These
      results suggest that prenatally testosterone-exposed mice may have deficits in
      synaptic development, and furthermore that the observed pathological features of
      their dendritic spines may be the cause of the synaptic pathogenesis in
      prenatally testosterone-exposed mice. 

PMID- 25953665
TI  - The selective mGluR5 agonist CHPG attenuates SO2-induced oxidative stress and
      inflammation through TSG-6/NF-kappaB pathway in BV2 microglial cells.
AB  - Sulfur dioxide (SO2) is a common air pollutant and can cause harmful insults on
      neurons. Microglial activation has been implicated in the signaling cascades that
      contribute to neuronal cell death in various neurological disorders. In the
      present study, we found that SO2 derivatives decreased cell viability via
      inducing oxidative stress, inflammatory responses and apoptotic cell death in BV2
      microglial cells. Pretreatment with (RS)-2-chloro-5-hydroxyphenylglycine (CHPG),
      an mGluR5 agonist, significantly attenuated the SO2-induced cytotoxicity, which
      was fully prevented by the mGluR5 antagonist MPEP. CHPG increased the expression
      of TNF-alpha stimulated gene/protein 6 (TSG-6), but decreased the activation of
      nuclear factor-kappaB (NF-kappaB) after SO2 derivatives treatment in BV2 cells.
      In addition, knockdown of TSG-6 expression by specific targeted short interfering
      RNA (siRNA) partially reversed the protection induced by CHPG. Therefore, our
      findings reveal a mechanistic basis for exploring the association between SO2
      exposure and neurological disorders, and also for opening up therapeutic
      approaches of ameliorating neuronal injury resulting from exposure in atmospheric
      polluting environment. 

PMID- 25953666
TI  - Monitoring of antibiotic consumption and development of resistance by
      enterobacteria in a tertiary care hospital.
AB  - WHAT IS KNOWN AND OBJECTIVE: Antibiotics are the most frequently used drugs in
      hospitalized patients, but studies have shown that the prescribed antibiotics may
      be inappropriate and may contribute to antibiotic resistance. We carried out a
      survey of antibiotic consumption and antibiotic resistance in our tertiary care
      university hospital, from 2005 to 2013. We focus on cephalosporins, one of the
      most prescribed groups of antibiotics in the tertiary health care. The objective
      was to identify any relationship between ceftriaxone consumption and resistance
      by enterobacteria. METHODS: Antibiotics consumption and antimicrobial resistance
      were monitored in the tertiary care university hospital from 2005 to 2013. Data
      on the use of antibiotics in surgical inpatients were obtained and expressed as
      defined daily doses per 100 bed days. Bacterial resistances were given as
      percentages of resistant isolates. RESULTS AND DISCUSSION: There was an
      increasing trend in cephalosporins consumption from 9.56 DBD (2005) to 23.32 DBD
      (2013), with ceftriaxone as the most frequently used cephalosporin, 3.6 DBD
      (2005) to 10.78 DBD (2013). E. coli and P. mirabilis resistance to ceftriaxone
      increased significantly from 22% in 2005 to 47% in 2013 and from 31% in 2005 to
      60% in 2013, respectively. We found a significant correlation between ceftriaxone
      consumption and E. coli resistance (r = 0.895, P < 0.05). WHAT IS NEW AND
      CONCLUSION: Our study shows that cephalosporin consumption increased from 2005 to
      2013, with ceftriaxone as the most prescribed antibiotic. E. coli and P.
      mirabilis resistance to ceftriaxone increased significantly over the study
      period. E. coli resistance increased with ceftriaxone consumption.

PMID- 25953667
TI  - Analysis of expression and chitin-binding activity of the wing disc cuticle
      protein BmWCP4 in the silkworm, Bombyx mori.
AB  - The insect exoskeleton is mainly composed of chitin filaments linked by cuticle
      proteins. When insects molt, the cuticle of the exoskeleton is renewed by
      degrading the old chitin and cuticle proteins and synthesizing new ones. In this
      study, chitin-binding activity of the wing disc cuticle protein BmWCP4 in Bombyx
      mori was studied. Sequence analysis showed that the protein had a conservative
      hydrophilic "R&R" chitin-binding domain (CBD). Western blotting showed that
      BmWCP4 was predominately expressed in the wing disc-containing epidermis during
      the late wandering and early pupal stages. The immunohistochemistry result showed
      that the BmWCP4 was mainly present in the wing disc tissues containing wing bud
      and trachea blast during day 2 of wandering stage. Recombinant full-length BmWCP4
      protein, "R&R" CBD peptide (CBD), non-CBD peptide (BmWCP4-CBD- ), four single
      site-directed mutated peptides (M1 , M2 , M3 and M4 ) and four-sites-mutated
      peptide (MF ) were generated and purified, respectively, for in vitro chitin
      binding assay. The results indicated that both the full-length protein and the
      "R&R" CBD peptide could bind with chitin, whereas the BmWCP4-CBD- could not bind
      with chitin. The single residue mutants M1 , M2 , M3 and M4 reduced but did not
      completely abolish the chitin-binding activity, while four-sites-mutated protein
      MF completely lost the chitin-binding activity. These data indicate that BmWCP4
      protein plays a critical role by binding to the chitin filaments in the wing
      during larva-to-pupa transformation. The conserved aromatic amino acids are
      critical in the interaction between chitin and the cuticle protein.

PMID- 25953668
TI  - Mapping and correcting the influence of gaze position on pupil size measurements.
AB  - Pupil size is correlated with a wide variety of important cognitive variables and
      is increasingly being used by cognitive scientists. Pupil data can be recorded
      inexpensively and non-invasively by many commonly used video-based eye-tracking
      cameras. Despite the relative ease of data collection and increasing prevalence
      of pupil data in the cognitive literature, researchers often underestimate the
      methodological challenges associated with controlling for confounds that can
      result in misinterpretation of their data. One serious confound that is often not
      properly controlled is pupil foreshortening error (PFE)-the foreshortening of the
      pupil image as the eye rotates away from the camera. Here we systematically map
      PFE using an artificial eye model and then apply a geometric model correction.
      Three artificial eyes with different fixed pupil sizes were used to
      systematically measure changes in pupil size as a function of gaze position with
      a desktop EyeLink 1000 tracker. A grid-based map of pupil measurements was
      recorded with each artificial eye across three experimental layouts of the eye
      tracking camera and display. Large, systematic deviations in pupil size were
      observed across all nine maps. The measured PFE was corrected by a geometric
      model that expressed the foreshortening of the pupil area as a function of the
      cosine of the angle between the eye-to-camera axis and the eye-to-stimulus axis.
      The model reduced the root mean squared error of pupil measurements by 82.5 %
      when the model parameters were pre-set to the physical layout dimensions, and by
      97.5 % when they were optimized to fit the empirical error surface.

PMID- 25953670
TI  - Aging, glucocorticoids and developmental programming.
AB  - Glucocorticoids are pleiotropic regulators of multiple cell types with critical
      roles in physiological systems that change across the life-course. Although
      glucocorticoids have been associated with aging, available data on the aging
      trajectory in basal circulating glucocorticoids are conflicting. A literature
      search reveals sparse life-course data. We evaluated (1) the profile of basal
      circulating corticosterone across the life-course from weaning (postnatal day-PND
      21), young adult PND 110, adult PND 450, mature adult PND 650 to aged phase PND
      850 in a well-characterized homogeneous rat colony to determine existence of
      significant changes in trajectory in the second half of life; (2) sex
      differences; and (3) whether developmental programming of offspring by exposure
      to maternal obesity during development alters the later-life circulating
      corticosterone trajectory. We identified (1) a fall in corticosterone between PND
      450 and 650 in both males and females (p < 0.05) and (2) higher female than male
      concentrations (p < 0.05). (3) Using our five life-course time-point data set,
      corticosterone fell at a similar age but from higher levels in male and female
      offspring of obese mothers. In all four groups studied, there was a second half
      of life fall in corticosterone. Higher corticosterone levels in offspring of
      obese mothers may play a role in their shorter life-span, but the age-associated
      fall occurs at a similar time to control offspring. Although even more life
      course time-points would be useful, a five life-course time-point analysis
      provides important new information on normative and programmed aging of
      circulating corticosterone.

PMID- 25953669
TI  - Female PAPP-A knockout mice are resistant to metabolic dysfunction induced by
      high-fat/high-sucrose feeding at middle age.
AB  - Longevity and aging are influenced by common intracellular signals of the
      insulin/insulin-like growth factor (IGF)-1 pathway. Abnormally high levels of
      bioactive IGF-1 increase the development of various cancers and may contribute to
      metabolic diseases such as insulin resistance. Enhanced availability of IGF-1 is
      promoted by cleavage of IGF binding proteins (IGFBPs) by proteases, including the
      pregnancy-associated plasma protein-A (PAPPA). In vitro, PAPP-A is regulated by
      pro-inflammatory cytokines (PICs) such as interleukin (IL)-6 and tumor necrosis
      factor (TNF). Mice born with deficiency of the Papp-a gene (PAPP-A knockout (KO)
      mice) live ~30-40 % longer than their normal littermates and have decreased
      bioactive IGF-1 on standard diets. Our objective was to elucidate how the effects
      of high-fat, high-sucrose diet (HFHS) promote obesity, induce metabolic
      dysfunction, and alter systemic cytokine expression in PAPP-A KO and normal mice.
      PAPP-A KO mice fed HFHS diet for 10 weeks were more glucose tolerant and had
      enhanced insulin sensitivity compared to normal mice fed HFHS diet. PAPP-A KO
      mice fed HFHS diet had lower levels of pro-inflammatory cytokines (IL-2, IL-6,
      and TNF-alpha) compared to normal mice fed the same diet. However, anti
      inflammatory cytokine levels (IL-4 and adiponectin) were higher in PAPP-A KO mice
      fed HFHS diet compared to normal mice fed HFHS. Circulating PAPP-A levels were
      elevated in normal mice fed an HFHS diet compared to normal mice fed a standard,
      low-fat, low-sucrose (LFLS) diet. Indirect calorimetry showed, at 10 weeks of
      feeding HFHS diet, significantly increased oxygen consumption (VO2) in PAPP-A KO
      mice fed HFHS diet compared to normal mice fed the same diet. Furthermore,
      respiratory quotient (RQ) was significantly lower in PAPP-A KO mice fed HFHS diet
      compared to normal (N) mice fed HFHS diet indicating PAPP-A KO mice fed HFHS diet
      are able to rely on fat as their primary source of energy more so than normal
      controls. We conclude that PAPP-A KO mice are resistant to the HFHS diet
      induction of metabolic dysfunction associated with higher levels of anti
      inflammatory cytokines and a remarkably metabolic flexible phenotype and that
      some of the effects of HFHS diet in normal animals may be due to increased levels
      of PAPP-A.

PMID- 25953671
TI  - Scald burns in children under 3 years: an analysis of NEISS narratives to inform
      a scald burn prevention program.
AB  - BACKGROUND OBJECTIVES: To determine the incidence of paediatric scald burns for
      children under 3 years of age treated in US hospital emergency departments. To
      quantify injury patterns associated with scald burns to inform prevention
      recommendation messaging. METHODS: The National Electronic Injury Surveillance
      System (NEISS) coding manual was reviewed for cause of injury. Its database was
      queried to identify cases among patients up to age 3 years old with a diagnosis
      of scald burns between 1 January 2009 and 31 December 2012. The resulting data
      set was downloaded and case narratives were reviewed to identify injury patterns
      associated with scald burns. RESULTS: The NEISS query identified 2104 scald burn
      cases between 2009 and 2012, yielding a national estimate of 11 028 scald burns
      in children younger than 3 years old annually. The analysis of the case
      narratives resulted in the identification of six precipitating and/or
      contributing factors including: grabbed/pulled, cooking, bathing, consuming,
      appliance and other. CONCLUSIONS: NEISS is a valuable tool to identify scald burn
      risks. The NEISS data system provided an opportunity to identify and examine
      scald burns in children under 3 years of age. Interpretation of NEISS results is
      limited due to the lack of consistency and detail in narratives about the injury
      event. Nevertheless, the information that was available on precipitating and/or
      contributing factors suggests that caretakers should test the temperature of
      their water heaters, test bath water before bathing children and be made aware of
      risk of scalds from hot liquids so that they exercise close supervision of
      children.

PMID- 25953672
TI  - The effectiveness of an exercise programme on knee loading, muscle co
      contraction, and pain in patients with medial knee osteoarthritis: A pilot study.
AB  - BACKGROUND: Osteoarthritis (OA), which increases knee loading, muscle co
      contraction, and pain, is a mechanical disease that requires biomechanical
      exploration to reduce pain in the knee. Therefore, this article aims to
      investigate the effectiveness of an exercise programme on the aforementioned
      outcomes in people with medial knee OA. METHODS: Cohort pilot study design. A
      total of 19 patients with knee OA attended a six-week group exercise programme
      integrated with self-management education. The following outcomes were assessed
      before and after the exercise programme: external knee adduction moment (EKAM),
      knee adduction angular impulse (KAAI), knee antagonist muscle co-contraction, and
      pain subscale of the knee injury and osteoarthritis outcome score (KOOS).
      RESULTS: Of the 19 patients, 14 completed the study. The EKAM and KAAI did not
      show statistical significance post-exercise intervention (p=0.21-0.7 and 0.56,
      respectively). Muscle co-contraction between vastus lateralis and biceps femoris
      muscles decreased in early-stance (64.78 (44.35) compared with 38.10 (23.10),
      p=0.01) and mid-stance (27.62 (32.12) compared with 14.94 (17.40), p=0.04). A
      corresponding significant pain reduction was observed (p=0.00) with a median
      (range) of 51.50 (47.00 to 62.50) at week 6 compared with 34.50 (29.25 to 41.25)
      at baseline. CONCLUSION: This is the first known study to explore the effect of
      an exercise programme on knee loading and muscle co-contraction in patients with
      OA. Although the value of EKAM did not change, the findings suggest that the
      reduction in vastus lateralis and biceps femoris co-contraction might be the
      mechanism behind the reduction of pain.

PMID- 25953674
TI  - Recent advances in understanding the pathophysiology of primary T cell
      immunodeficiencies.
AB  - Primary immunodeficiencies (PIDs) constitute a large group of rare disorders that
      affect the function of the immune system. These deficiencies are usually
      associated with inability to prevent infections but can also result in allergy,
      inflammation, autoimmunity, and cancer. The recent characterization of many
      different monogenic defects has shed light on a range of non-redundant
      differentiation, effector, and regulatory functions of immune cells. The present
      review focuses on PIDs that affect adaptive immunity in general and T lymphocytes
      in particular. The analysis of PIDs is now opening up new pathways towards
      targeted therapies. 

PMID- 25953673
TI  - Metastasis-associated in colon cancer 1 is an independent prognostic biomarker
      for survival in Klatskin tumor patients.
AB  - Curative treatment of intrahepatic cholangiocarcinoma (ICC) and hilar
      cholangiocarcinoma (Klatskin tumors) is limited to surgical resection or
      orthotopic liver transplantation. However, not all patients benefit from a
      surgical approach and suffer from early tumor recurrence. Response to
      chemotherapy is generally poor and, until today, no targeted therapy could be
      established. Metastasis-associated in colon cancer 1 (MACC1) is a recently
      discovered regulator of the hepatocyte growth factor (HGF)/Met/mitogen-activated
      protein kinase pathway, which induces proliferation, migration, and invasion in
      cell culture, as well as metastasis in mice. MACC1 expression shows a significant
      correlation with Met expression in colon cancer tissue and is highly prognostic
      for occurrence of distant metastasis and survival in colon cancer patients. Thus,
      we aimed to measure the expression of MACC1, Met, and HGF messenger RNA in
      microdissected tumor tissue and corresponding normal liver tissue of 156 patients
      with Klatskin tumors (n = 76) and ICC (n = 80) using real-time quantitative
      reverse-transcriptase polymerase chain reaction. We used immunohistochemical
      staining to validate the results. MACC1 expression in tumor tissue of both tumor
      entities was significantly higher than in corresponding normal liver tissue (P <
      0.001). Klatskin tumor patients with a history of tumor recurrence had
      significantly higher MACC1 expression than those without tumor recurrence (P =
      0.005). Uni- und multivariate survival analysis showed that Klatskin tumor
      patients with high MACC1 had a significantly shorter overall (OS) and disease
      free survival (DFS; P = 0.001 and P < 0.001, respectively). The multivariate
      analysis confirmed MACC1 to be an independent factor for overall survival in
      Klatskin tumor patients (hazard ratio: 2.777; 95% confidence interval: 1.389
      5.555; P = 0.004). CONCLUSION: Our study identified MACC1 as a highly prognostic
      biomarker for OS and DFS in Klatskin tumor patients. MACC1 expression could
      become an important diagnostic tool and might be a candidate for targeted
      therapy.

PMID- 25953675
TI  - Use of the Impella 2.5 left ventricular assist device in a patient with
      cardiogenic shock secondary to takotsubo cardiomyopathy.
AB  - We report a case of cardiogenic shock, believed to be secondary to stress-induced
      cardiomyopathy, managed by an Impella 2.5 assist device. Apical ballooning
      pattern was evident on left ventriculogram with no significant coronary artery
      disease on coronary angiography. Cardiogenic shock was initially managed
      medically with inotropes and vasopressors, but because the patient was clinically
      deteriorating, an Impella 2.5 left ventricular assist device was implanted.
      Remarkable recovery occurred within 48 h of implantation with significant
      increase in ejection fraction and only minimal residual apical hypokinesis
      observed on repeat ventriculogram. 

PMID- 25953676
TI  - Superdominant left-circumflex artery supplying significant proportion of RCA and
      LAD territory.

PMID- 25953677
TI  - Short-Term Effect of Autologous Bone Marrow Stem Cells to Treat Acute Myocardial
      Infarction: A Meta-Analysis of Randomized Controlled Clinical Trials.
AB  - Bone marrow stem cells (BMSCs) have been used to treat patient with ST-segment
      elevation myocardial infarction (STEMI) via intracoronary route. We performed a
      meta-analysis to evaluate the short-term efficacy and safety of this modality.
      Seventeen randomized controlled trials (RCTs) of BMSC-based therapy for STEMI,
      delivered with 9 days of reperfusion and followed up shorter than 12 months, were
      identified by systematic review. Intracoronary BMSC therapy resulted in an
      overall significant improvement in left ventricular ejection fraction (LVEF) by
      2.74 % (95 % confidence interval (CI) 2.09-3.39, P < 0.00001, I(2) = 84 %) at 3-6
      month follow-up and 5.1 % (95 % CI 4.16-6.03, P < 0.00001 and I(2) = 85 %) at 12
      months. The left ventricular end-systolic volume (LVESV) and wall motion score
      index (WMSI) were also reduced at 3-6 months. At 12 months, left ventricular end
      diastolic volume (LVEDV), LVESV, and WMSI were significantly reduced in BMSC
      group. In conclusion, intracoronary BMSC therapy at post-STEMI is safe and
      effective in patient with acute STEMI.

PMID- 25953678
TI  - Molecular pathogenesis of multiple myeloma.
AB  - Multiple myeloma (MM), one of the most intractable malignancies, is characterized
      by the infiltration and growth of plasma cells, the most differentiated cells in
      the B-cell lineage, in the bone marrow. Despite the introduction of novel
      therapeutic agents, including proteasome inhibitors and immunomodulatory drugs,
      the prognosis of patients with MM is still worse than that of most hematological
      malignancies. A better understanding of the molecular pathogenesis of the disease
      is essential to achieve any improvement of treatment outcome of MM patients. All
      MM cases pass through the phase of asymptomatic expansion of clonal plasma cells,
      referred to as monoclonal gammopathy of undetermined significance (MGUS). It has
      long been believed that MM evolves linearly from MGUS to terminal phases, such as
      extramedullary tumors and plasma cell leukemia via the accumulation of novel
      mutations. However, recent studies using next-generation sequencing have
      disclosed the complex genomic architecture of the disease. At each step of
      progression, the acquisition of novel mutations is accompanied by subclonal
      evolution from reservoir clones with branching patterns. Each subclone may carry
      novel mutations and distinct phenotypes, including drug sensitivity. In addition,
      minor clones already exist at the MGUS stage, which could expand later in the
      clinical course, resulting in relapse and/or leukemic conversion. The ultimate
      goal of treatment is to eradicate all clones, including subclonal populations
      with distinct biological characteristics. This goal could be achieved by further
      improving treatment strategies that reflect the genomic landscape of the disease.

PMID- 25953679
TI  - Gefitinib treatment in patients with postoperative recurrent non-small-cell lung
      cancer harboring epidermal growth factor receptor gene mutations.
AB  - BACKGROUND: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor
      gefitinib is an effective treatment for recurrent or advanced lung cancer
      harboring EGFR gene mutations, and has improved progression-free survival in
      several clinical trials. However, the effect of gefitinib treatment for recurrent
      lung cancers with EGFR gene mutations after complete resection and the influence
      of the timing of such treatment have not been fully elucidated in a practical
      setting. METHODS: We investigated 64 patients (median age: 68 years; men: 22;
      women: 42; adenocarcinoma: 61; adenosquamous cell carcinoma: 2; combined large
      cell neuroendocrine carcinoma: 1) with recurrent lung cancer after complete
      resection who received gefitinib for the recurrent lesions and in whom the tumors
      had EGFR gene mutations. Progression-free survival, response rate, and safety
      were analyzed. RESULTS: Complete response and partial response were achieved in 2
      patients and in 42 patients, respectively (objective response rate: 69 %). Stable
      disease was obtained in 16 patients, the disease control rate was 94 %, and
      median progression-free survival was 16 months. The timing of gefitinib treatment
      (first line, second line, or later) and the type of EGFR gene mutation present
      did not influence progression-free survival. However, a smaller number of
      recurrent sites at the start of gefitinib treatment was linked to better
      progression-free survival. Hematologic and nonhematologic toxicities were
      generally mild, but 1 patient experienced interstitial lung disease. CONCLUSIONS:
      Our results suggest that gefitinib treatment for recurrent lung cancer with gene
      EGFR mutations is a useful option in a practical setting, irrespective of the
      timing of such treatment and the type of EGFR gene mutation present.

PMID- 25953680
TI  - Clinical response to induction chemotherapy predicts improved survival outcome in
      urothelial carcinoma with clinical lymph nodal metastasis treated by
      consolidative surgery.
AB  - BACKGROUND: To determine the indications for post-chemotherapy consolidative
      surgery in patients with clinical lymph node (LN) metastatic (cN+) urothelial
      carcinoma (UC). METHODS: Sixty UC patients with measurable cN+ but without
      detectable systemic visceral/bone dissemination received induction platinum-based
      chemotherapy. Consolidative surgery was offered to all patients except for those
      with progressive disease. We retrospectively analyzed the clinicopathological
      response to induction chemotherapy and identified prognostic factors for overall
      survival (OS). RESULTS: The primary cancer site was the urinary bladder in 31
      patients (52 %) and upper urinary tract in 29 (48 %). The median number of
      chemotherapy courses was 4. Forty-five patients (75 %) showed a clinically
      objective response to the induction chemotherapy. Fifty-one patients (85 %)
      underwent subsequent consolidative surgery. Histopathological analysis indicated
      pT0 status in 10 (20 %) and pN0 in 17 (33 %). When all 60 patients were
      considered, clinical tumor response was found to be significantly correlated with
      achievement of pathological complete response. At the median follow-up of 22
      months, the median progression-free survival and OS periods were excellent: 18.6
      and 31.6 months, respectively. In the multivariate analysis, clinical tumor
      response was found to be an independent pre-surgical prognostic factor for OS,
      and pathologically negative lymph node, negative resection margin, more LNs
      removed, and negative lymphovascular invasion were found to be independent post
      surgical prognostic parameters for OS. CONCLUSIONS: The median OS in induction
      chemotherapy followed by consolidative surgery was very encouraging. Our results
      suggest that achieving a good clinical response to pre-surgical induction
      chemotherapy is a good indication for subsequent consolidative surgery in UC
      patients with cN+ to improve OS through a good pathological response.

PMID- 25953681
TI  - Behavioural neuroscience: Picking up the pups.

PMID- 25953682
TI  - Cytocompatibility evaluation of NiMnSn meta-magnetic shape memory alloys for
      biomedical applications.
AB  - Recently, magnetic shape memory alloys (MSMAs) have emerged as an interesting
      extension to conventional shape memory alloys (SMAs) due to their capacity to
      undergo reversible deformation in response to an externally applied magnetic
      field. Meta-magnetic SMAs (M-MSMAs) are a class of MSMAs that are able to
      transform magnetic energy to mechanical work by harnessing a magnetic-field
      induced phase transformation, and thus have the capacity to impose up to 10 times
      greater stress than conventional MSMAs. As such, M-MSMAs may hold substantial
      promise in biomedical applications requiring extracorporeal device activation. In
      the present study, the cytotoxicity and ion release from an Ni50 Mn36 Sn14 atomic
      percent composition M-MSMA were evaluated using NIH/3T3 fibroblasts. Initial
      studies showed that the viability of cells exposed to NiMnSn ion leachants was 60
      to 67% of tissue culture polystyrene (TCP) controls over 10 to 14 days of
      culture. This represents a significant improvement in cytocompatibility relative
      to NiMnGa alloys, one of the most extensively studied MSMA systems, which have
      been reported to induce 80% cell death in only 48 h. Furthermore, NiMnSn M-MSMA
      associated cell viability was increased to 80% of TCP controls following layer-by
      layer alloy coating with poly(allylamine hydrochloride)/poly(acrylic acid)
      [PAH/PAA]. Ion release measures revealed that the PAH/PAA coatings decreased
      total Sn and Mn ion release by 50% and 25%, respectively, and optical microscopy
      evaluation indicated that the coatings reduced NiMnSn surface oxidation. To our
      knowledge, this study presents the first cytotoxicity evaluation of NiMnSn M
      MSMAs and lays the groundwork for their further biological evaluation. (c) 2015
      Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 853-863,
      2016.

PMID- 25953683
TI  - Surface behavior of amphiphiles in aqueous solution: a comparison between
      different pentanol isomers.
AB  - Position isomerism is ubiquitous in atmospheric oxidation reactions. Therefore,
      we have compared surface-active oxygenated amphiphilic isomers (1- and 3
      pentanol) at the aqueous surface with surface- and chemically sensitive X-ray
      photoelectron spectroscopy (XPS), which reveals information about the surface
      structure on a molecular level. The experimental data are complemented with
      molecular dynamics (MD) simulations. A concentration-dependent orientation and
      solvation of the amphiphiles at the aqueous surface is observed. At bulk
      concentrations as low as around 100 mM, a monolayer starts to form for both
      isomers, with the hydroxyl groups pointing towards the bulk water and the alkyl
      chains pointing towards the vacuum. The monolayer (ML) packing density of 3
      pentanol is approx. 70% of the one observed for 1-pentanol, with a molar surface
      concentration that is approx. 90 times higher than the bulk concentration for
      both molecules. The molecular area at ML coverage (~100 mM) was calculated to be
      around 32 +/- 2 A(2) per molecule for 1-pentanol and around 46 +/- 2 A(2) per
      molecule for 3-pentanol, which results in a higher surface concentration
      (molecules per cm(2)) for the linear isomer. In general we conclude therefore
      that isomers - with comparable surface activities - that have smaller molecular
      areas will be more abundant at the interface in comparison to isomers with larger
      molecular areas, which might be of crucial importance for the understanding of
      key properties of aerosols, such as evaporation and uptake capabilities as well
      as their reactivity. 

PMID- 25953684
TI  - Chromosome fragility at FRAXA in human cleavage stage embryos at risk for fragile
      X syndrome.
AB  - Fragile X syndrome (FXS), the most common inherited intellectual disability
      syndrome, is caused by expansion and hypermethylation of the CGG repeat in the 5'
      UTR of the FMR1 gene. This expanded repeat, also known as the rare fragile site
      FRAXA, causes X chromosome fragility in cultured cells from patients but only
      when induced by perturbing pyrimidine synthesis. We performed preimplantation
      genetic diagnosis (PGD) on 595 blastomeres biopsied from 442 cleavage stage
      embryos at risk for FXS using short tandem repeat (STR) markers. In six
      blastomeres, from five embryos an incomplete haplotype was observed with loss of
      all alleles telomeric to the CGG repeat. In all five embryos, the incomplete
      haplotype corresponded to the haplotype carrying the CGG repeat expansion.
      Subsequent analysis of additional blastomeres from three embryos by array
      comparative genomic hybridization (aCGH) confirmed the presence of a terminal
      deletion with a breakpoint close to the CGG repeat in two blastomeres from one
      embryo. A blastomere from another embryo showed the complementary duplication. We
      conclude that a CGG repeat expansion at FRAXA causes X chromosome fragility in
      early human IVF embryos at risk for FXS.

PMID- 25953685
TI  - Deoxycholate-Based Glycosides (DCGs) for Membrane Protein Stabilisation.
AB  - Detergents are an absolute requirement for studying the structure of membrane
      proteins. However, many conventional detergents fail to stabilise denaturation
      sensitive membrane proteins, such as eukaryotic proteins and membrane protein
      complexes. New amphipathic agents with enhanced efficacy in stabilising membrane
      proteins will be helpful in overcoming the barriers to studying membrane protein
      structures. We have prepared a number of deoxycholate-based amphiphiles with
      carbohydrate head groups, designated deoxycholate-based glycosides (DCGs). These
      DCGs are the hydrophilic variants of previously reported deoxycholate-based N
      oxides (DCAOs). Membrane proteins in these agents, particularly the branched
      diglucoside-bearing amphiphiles DCG-1 and DCG-2, displayed favourable behaviour
      compared to previously reported parent compounds (DCAOs) and conventional
      detergents (LDAO and DDM). Given their excellent properties, these agents should
      have significant potential for membrane protein studies. 

PMID- 25953687
TI  - Markers of progression in early-stage invasive breast cancer: a predictive
      immunohistochemical panel algorithm for distant recurrence risk stratification.
AB  - Accurate distant metastasis (DM) prediction is critical for risk stratification
      and effective treatment decisions in breast cancer (BC). Many prognostic
      markers/models based on tissue marker studies are continually emerging using
      conventional statistical approaches analysing complex/dimensional data
      association with DM/poor prognosis. However, few of them have fulfilled
      satisfactory evidences for clinical application. This study aimed at building DM
      risk assessment algorithm for BC patients. A well-characterised series of early
      invasive primary operable BC (n = 1902), with immunohistochemical expression of a
      panel of biomarkers (n = 31) formed the material of this study. Decision tree
      algorithm was computed using WEKA software, utilising quantitative biomarkers'
      expression and the absence/presence of distant metastases. Fifteen biomarkers
      were significantly associated with DM, with six temporal subgroups characterised
      based on time to development of DM ranging from <1 to >15 years of follow-up. Of
      these 15 biomarkers, 10 had a significant expression pattern where Ki67LI, HER2,
      p53, N-cadherin, P-cadherin, PIK3CA and TOMM34 showed significantly higher
      expressions with earlier development of DM. In contrast, higher expressions of
      ER, PR and BCL2 were associated with delayed occurrence of DM. DM prediction
      algorithm was built utilising cases informative for the 15 significant markers.
      Four risk groups of patients were characterised. Three markers p53, HER2 and BCL2
      predicted the probability of DM, based on software-generated cut-offs, with a
      precision rate of 81.1 % for positive predictive value and 77.3 %, for the
      negative predictive value. This algorithm reiterates the reported prognostic
      values of these three markers and underscores their central biological role in BC
      progression. Further independent validation of this pruned panel of biomarkers is
      therefore warranted.

PMID- 25953686
TI  - Body mass index associated with genome-wide methylation in breast tissue.
AB  - Gene expression studies indicate that body mass index (BMI) is associated with
      molecular pathways involved in inflammation, insulin-like growth factor
      activation, and other carcinogenic processes in breast tissue. The goal of this
      study was to determine whether BMI is associated with gene methylation in breast
      tissue and to identify pathways that are commonly methylated in association with
      high BMI. Epigenome-wide methylation profiles were determined using the Illumina
      HumanMethylation450 BeadChip array in the non-diseased breast tissue of 81 women
      undergoing breast surgery between 2009 and 2013 at the University of North
      Carolina Hospitals. Multivariable, robust linear regression was performed to
      identify methylation sites associated with BMI at a false discovery rate q value
      <0.05. Gene expression microarray data was used to identify which of the BMI
      associated methylation sites also showed correlation with gene expression. Gene
      set enrichment analysis was conducted to assess which pathways were enriched
      among the BMI-associated methylation sites. Of the 431,568 methylation sites
      analyzed, 2573 were associated with BMI (q value <0.05), 57 % of which showed an
      inverse correlation with BMI. Pathways enriched among the 2573 probe sites
      included those involved in inflammation, insulin receptor signaling, and leptin
      signaling. We were able to map 1251 of the BMI-associated methylation sites to
      gene expression data, and, of these, 226 (18 %) showed substantial correlations
      with gene expression. Our results suggest that BMI is associated with genome-wide
      methylation in non-diseased breast tissue and may influence epigenetic pathways
      involved in inflammatory and other carcinogenic processes.

PMID- 25953688
TI  - Invasive micropapillary mucinous carcinoma of the breast is associated with poor
      prognosis.
AB  - Invasive micropapillary carcinoma of breast (IMpC) is a special type of breast
      cancer with frequent lymph node metastasis (LNM) and poor prognosis, while pure
      mucinous carcinoma of breast (PMC) is generally associated with infrequent LNM
      and better prognosis. A similar micropapillary epithelial growth pattern has been
      described in PMC that was named as invasive micropapillary mucinous carcinoma
      (IMpMC), but its prognostic significance is as yet not known. A retrospective
      review of 531 cases of PMC in 43,685 cases of breast cancer diagnosed over a 10
      year period was conducted to assess the frequency of IMpMC and its prognostic
      implications. IMpMC was identified in 134 (25.2 %) of the 531 PMC cases. Compared
      to conventional PMC (cPMC), IMpMC was found more frequently in younger patients
      and in tumors with increased frequency of LNM and lymphovascular invasion, and
      higher HER2 expression. In stage-matched Kaplan-Meier analysis, patients with
      stage II-III IMpMC suffered a decreased overall survival and recurrence-free
      survival (RFS) than matched cPMC patients. Multivariate analysis confirmed the
      presence of IMpMC morphology was an independent unfavorable predictor for LNM and
      RFS of PMC. However, decreased LNM, lower nuclear grade, higher expression of ER
      and PR, less expression of HER2, and better prognosis were identified in IMpMC
      when compared with IMpC (n = 281). This is the first study to show the prognostic
      significance of IMpMC in a large cohort. IMpMC pursues a more aggressive clinical
      course than cPMC and should be managed differently; therefore, recognition of
      IMpMC and its accurate diagnosis are clinically important.

PMID- 25953689
TI  - Vented spikes improve delivery from intravenous bags with no air headspace.
AB  - Flexible plastic bags are the container of choice for most intravenous (i.v.)
      infusions. Under certain circumstances, however, the air-liquid interface present
      in these i.v. bags can lead to physical instability of protein
      biopharmaceuticals, resulting in product aggregation. In principle, the air
      headspace present in the bags can be removed to increase drug stability, but
      experiments described here show that this can result in incomplete draining of
      solution from the bag using gravity delivery, or generation of negative pressure
      in the bag when an infusion pump is used. It is expected that these issues could
      lead to incomplete delivery of medication to patients or pump-related problems,
      respectively. However, here it is shown that contrary to the standard pharmacy
      practice of using nonvented spikes with i.v. bags, the use of vented spikes with
      i.v. bags that lack air headspace allows complete delivery of the dose solution
      without impacting the physical stability of a protein-based drug.

PMID- 25953691
TI  - Conformational analysis on the wild type and mutated forms of human ORF1p: a
      molecular dynamics study.
AB  - The protein ORF1p, encoded by the LINE-1 retrotransposon, is responsible for the
      packaging and transposition of its RNA transcript and is reported to be involved
      in various genetic disorders. The three domains of ORF1p co-ordinate together to
      facilitate the transposition, and the mechanism of nucleic acid binding is not
      yet clear. The C-terminal domain of ORF1p adopts a lifted, twisted or rested
      state, which is regulated by several inter- and intra-domain interactions that
      are explored in this study. The residues, Glu147, Asp151, Lys154, Arg261 and
      Tyr282, are majorly involved in mediating the functional dynamics of ORF1p by
      forming H-bonds and pi-interactions. The importance of these residues was
      elucidated by performing molecular dynamics simulations on both native as well as
      mutated ORF1p. The Q147A-D151A-K154A mutant expressed unique dynamics featuring
      the lifting motion of the CTD core alone, while the R261A mutant resulted in the
      oscillatory motion of CTD. In both cases, the CTDs were held in place by Tyr282
      and in its absence, the structural stability of CTDs in the trimeric unit was
      significantly affected. Additional interactions responsible for stabilizing the
      trimeric ORF1p to express its native dynamics were extracted in this study. The
      central role of Tyr282 in maintaining the functional state of ORF1p to facilitate
      nucleic acid binding and formation of ribonucleoprotein complex is well
      highlighted. The knowledge gained from this study forms the basis for
      understanding the nucleic acid binding mechanism of ORF1p, which could further
      provide additional support in exploring various genetic disorders. 

PMID- 25953692
TI  - The role of renal nerves in cardiovascular and renal function in normal and
      pathophysiological states.

PMID- 25953696
TI  - Recidivism in sexual offenders.

PMID- 25953695
TI  - Thyroid diseases in pregnancy: a current and controversial topic on diagnosis and
      treatment over the past 20 years.
AB  - BACKGROUND: Management of thyroid diseases during pregnancy requires special
      considerations because maternal thyroid diseases can have adverse effects on both
      pregnancy and fetus. Universal screening for thyroid diseases in pregnant women
      is not currently supported by studies with high evidence whereas guidelines have
      been released for individuals at high risk, although controversies are still in
      debate. Iodine prophylaxis should be performed systematically to women during
      pregnancy. MATERIALS AND METHODS: An electronic search of PubMed/Medline and
      EMBASE concerning thyroid diseases and pregnancy have been conducted over the
      past 20 years and summarized. RESULTS: Data regarding prevention and treatment of
      thyroid diseases during pregnancy are reported from analysis of the literature.
      CONCLUSIONS: As thyroid dysfunction may cause profound impact on mother's and
      fetus's health, implementation by strict application of clinico-diagnostic
      flowchart and recommendations is of paramount importance when dealing with
      thyroid diseases during pregnant state.

PMID- 25953690
TI  - Immunomodulatory Peptide IDR-1018 Decreases Implant Infection and Preserves
      Osseointegration.
AB  - BACKGROUND: Innate defense regulator peptide-1018 (IDR-1018) is a 12-amino acid,
      synthetic, immunomodulatory host defense peptide that can reduce soft tissue
      infections and is less likely to induce bacterial resistance than conventional
      antibiotics. However, IDRs have not been tested on orthopaedic infections and the
      immunomodulatory effects of IDR-1018 have only been characterized in response to
      lipopolysacharide, which is exclusively produced by Gram-negative bacteria.
      QUESTIONS/PURPOSES: We sought (1) to more fully characterize the immunomodulatory
      effects of IDR-1018, especially in response to Staphylococcus aureus; and (2) to
      determine whether IDR-1018 decreases S aureus infection of orthopaedic implants
      in mice and thereby protects the implants from failure to osseointegrate.
      METHODS: In vitro effects of IDR-1018 on S aureus were assessed by determining
      minimum inhibitory concentrations in bacterial broth without and with
      supplementation of physiologic ion levels. In vitro effects of IDR-1018 on
      macrophages were determined by measuring production of monocyte chemoattractant
      protein-1 (MCP-1) and proinflammatory cytokines by enzyme-linked immunosorbent
      assay. In vivo effects of IDR-1018 were determined in a murine model of S aureus
      implant infection by quantitating bacterial burden, macrophage recruitment, MCP
      1, proinflammatory cytokines, and osseointegration in nine mice per group on Day
      1 postimplantation and 20 mice per group on Day 15 postimplantation. RESULTS: IDR
      1018 demonstrated antimicrobial activity by directly killing S aureus even in the
      presence of physiologic ion levels, increasing recruitment of macrophages to the
      site of infections by 40% (p = 0.036) and accelerating S aureus clearance in vivo
      (p = 0.008) with a 2.6-fold decrease in bacterial bioburden on Day 7
      postimplantation. In vitro immunomodulatory activity of IDR-1018 included
      inducing production of MCP-1 in the absence of other inflammatory stimuli and to
      potently blunt excess production of proinflammatory cytokines and MCP-1 induced
      by lipopolysaccharide. Higher concentrations of IDR-1018 were required to blunt
      production of proinflammatory cytokines and MCP-1 in the presence S aureus. The
      largest in vivo immunomodulatory effect of IDR-1018 was to reduce tumor necrosis
      factor-alpha levels induced by S aureus by 60% (p = 0.006). Most importantly, IDR
      1018 reduced S aureus-induced failures of osseointegration by threefold (p =
      0.022) and increased osseointegration as measured by ultimate force (5.4-fold, p
      = 0.033) and average stiffness (4.3-fold, p = 0.049). CONCLUSIONS: IDR-1018 is
      potentially useful to reduce orthopaedic infections by directly killing bacteria
      and by recruiting macrophages to the infection site. CLINICAL RELEVANCE: These
      findings make IDR-1018 an attractive candidate to explore in larger animal models
      to ascertain whether its effects in our in vitro and mouse experiments can be
      replicated in more clinically relevant settings.

PMID- 25953697
TI  - Advanced (stage D) heart failure: a statement from the Heart Failure Society of
      America Guidelines Committee.
AB  - We propose that stage D advanced heart failure be defined as the presence of
      progressive and/or persistent severe signs and symptoms of heart failure despite
      optimized medical, surgical, and device therapy. Importantly, the progressive
      decline should be primarily driven by the heart failure syndrome. Formally
      defining advanced heart failure and specifying when medical and device therapies
      have failed is challenging, but signs and symptoms, hemodynamics, exercise
      testing, biomarkers, and risk prediction models are useful in this process.
      Identification of patients in stage D is a clinically important task because
      treatments are inherently limited, morbidity is typically progressive, and
      survival is often short. Age, frailty, and psychosocial issues affect both
      outcomes and selection of therapy for stage D patients. Heart transplant and
      mechanical circulatory support devices are potential treatment options in select
      patients. In addition to considering indications, contraindications, clinical
      status, and comorbidities, treatment selection for stage D patients involves
      incorporating the patient's wishes for survival versus quality of life, and
      palliative and hospice care should be integrated into care plans. More research
      is needed to determine optimal strategies for patient selection and medical
      decision making, with the ultimate goal of improving clinical and patient
      centered outcomes in patients with stage D heart failure. 

PMID- 25953699
TI  - Markers of atherosclerosis in relation to presence and progression of knee
      osteoarthritis: a population-based cohort study.
AB  - OBJECTIVES: To investigate the association between markers of atherosclerosis and
      the presence and progression of knee OA in a population-based cohort study.
      METHODS: The study was performed within the framework of the prospective
      Rotterdam Study. Markers of atherosclerosis included coronary artery
      calcification (CAC) and plasma levels of CD40L, vascular cell adhesion molecule 1
      (VCAM-1) and VEGF. CAC data were available for 1669 participants, and CD40L, VCAM
      1 and VEGF data for 975. Radiographs of the knee were scored with the Kellgren
      and Lawrence score for OA at baseline and follow-up [average follow-up time 4.5
      years (s.d. 0.5)]. We used multivariate logistic regression models with
      generalized estimated equations to calculate odds ratios (95% CIs) for the
      association of atherosclerosis markers with prevalence and progression of knee
      OA. RESULTS: The mean age was 73.1 (s.d. 7.5) years. Within the study population,
      18% had radiographic knee OA (11% of men and 23% of women). CAC and VEGF were not
      associated with prevalent knee OA. Only among women, CD40L [adjusted odds ratio
      1.3 (1.1, 1.6)] and VCAM-1 [adjusted odds ratio 1.3 (1.1, 1.6)] were associated
      with prevalent knee OA. No associations with progression were found in women. In
      men, too few progressors were available to assess associations. CONCLUSION: In
      this population-based study, CAC and VEGF were not associated with the presence
      or progression of knee OA. Only among women, plasma levels of CD40L and VCAM-1
      were higher in individuals with knee OA compared with those without knee OA. This
      might suggest an association between atherosclerosis and knee OA through low
      grade systemic inflammation in women.

PMID- 25953700
TI  - Haematopoietic stem cell transplantation for poor-prognosis systemic sclerosis.
AB  - Haematopoietic stem cell transplantation (HSCT) following intensive immune
      suppression has been used in >2000 patients with severe autoimmune diseases for
      18 years, including 300 with SSc. The concept is to profoundly reduce the bulk of
      auto-aggressive immune competent cells and then rescue the patient's ablated
      haematopoiesis via an autologous HSCT. An early analysis of uncontrolled phase
      I/II data suggested that approximately one-third of these achieved a substantial
      improvement, with a relapse rate of 25% and a treatment-related mortality ranging
      from 6% to 23% across different studies. These early results led to three
      prospective randomized controlled trials, two of which are completed, confirming
      that HSCT shows clear advantages over conventional immunosuppression, but with
      significant toxicity. In some patients, sustained complete normalization of skin
      changes, reversal of positive autoantibody status and withdrawal of
      immunosuppressive medication were observed. These results attest to the profound
      effects of HSCT.

PMID- 25953698
TI  - Dimethyl fumarate induces necroptosis in colon cancer cells through GSH
      depletion/ROS increase/MAPKs activation pathway.
AB  - BACKGROUND AND PURPOSE: Dimethyl fumarate (DMF) is a newly approved drug for the
      treatment of relapsing forms of multiple sclerosis and relapsing-remitting
      multiple sclerosis. Here, we investigated the effects of DMF and its metabolites
      mono-methylfumarate (MMF and methanol) on different gastrointestinal cancer cell
      lines and the underlying molecular mechanisms involved. EXPERIMENTAL APPROACH:
      Cell viability was measured by the MTT or CCK8 assay. Protein expressions were
      measured by Western blot analysis. LDH release, live- and dead-cell staining,
      intracellular GSH levels, and mitochondrial membrane potential were examined by
      using commercial kits. KEY RESULTS: DMF but not MMF induced cell necroptosis, as
      demonstrated by the pharmacological tool necrostatin-1, transmission electron
      microscopy, LDH and HMGB1 release in CT26 cells. The DMF-induced decrease in
      cellular GSH levels as well as cell viability and increase in reactive oxygen
      species (ROS) were inhibited by co-treatment with GSH and N-acetylcysteine (NAC)
      in CT26 cells. DMF activated JNK, p38 and ERK MAPKs in CT26 cells and JNK, p38
      and ERK inhibitors partially reversed the DMF-induced decrease in cell viability.
      GSH or NAC treatment inhibited DMF-induced JNK, p38, and ERK activation in CT26
      cells. DMF but not MMF increased autophagy responses in SGC-7901, HCT116, HT29
      and CT26 cancer cells, but autophagy inhibition did not prevent the DMF-induced
      decrease in cell viability. CONCLUSION AND IMPLICATIONS: DMF but not its
      metabolite MMF induced necroptosis in colon cancer cells through a mechanism
      involving the depletion of GSH, an increase in ROS and activation of MAPKs.

PMID- 25953701
TI  - T1 Relaxation Rate (R1) Indicates Nonlinear Mn Accumulation in Brain Tissue of
      Welders With Low-Level Exposure.
AB  - Although the essential element manganese (Mn) is neurotoxic at high doses, the
      effects of lower exposure are unclear. MRI T1-weighted (TIW) imaging has been
      used to estimate brain Mn exposure via the pallidal index (PI), defined as the
      T1W intensity ratio in the globus pallidus (GP) versus frontal white matter
      (FWM). PI may not, however, be sensitive to Mn in GP because Mn also may
      accumulate in FWM. This study explored: (1) whether T1 relaxation rate (R1) could
      quantify brain Mn accumulation more sensitively; and (2) the dose-response
      relationship between estimated Mn exposure and T1 relaxation rate (R1). Thirty
      five active welders and 30 controls were studied. Occupational questionnaires
      were used to estimate hours welding in the past 90 days (HrsW) and lifetime
      measures of Mn exposure. T1W imaging and T1-measurement were utilized to generate
      PI and R1 values in brain regions of interest (ROIs). PI did not show a
      significant association with any measure of Mn and/or welding-related exposure.
      Conversely, in several ROIs, R1 showed a nonlinear relationship to HrsW, with R1
      signal increasing only after a critical exposure was reached. The GP had the
      greatest rate of Mn accumulation. Welders with higher exposure showed
      significantly higher R1 compared either with controls or with welders with lower
      exposure. Our data are additional evidence that Mn accumulation can be assessed
      more sensitively by R1 than by PI. Moreover, the nonlinear relationship between
      welding exposure and Mn brain accumulation should be considered in future studies
      and policies. 

PMID- 25953703
TI  - In Vitro, Ex Vivo, and In Vivo Determination of Thyroid Hormone Modulating
      Activity of Benzothiazoles.
AB  - As in vitro assays are increasingly used to screen chemicals for their potential
      to produce endocrine disrupting adverse effects, it is important to understand
      their predictive capacity. The potential for a set of 6 benzothiazoles to affect
      endpoints related to thyroid hormone synthesis inhibition were assessed using in
      vitro, ex vivo, and in vivo assays. Inhibition of thyroid peroxidase (TPO)
      derived from pig thyroid glands was determined for benzothiazole (BTZ), 2
      mercaptobenzothiazole (MBT), 5-chloro-2-mercaptobenzothiazole (CMBT), 2
      aminobenzothiazole (ABT), 2-hydroxybenzothiazole (HBT), and 2
      methylthiobenzothiazole (MTBT). Their rank order potency for TPO inhibition was
      MBT=CMBT>ABT>BTZ, whereas HBT and MTBT exhibited no inhibitory activity. The
      benzothiazoles were tested further in a Xenopus laevis thyroid gland explant
      culture assay in which inhibition of thyroxine (T4) release was the measured
      endpoint. In this assay all 6 benzothiazoles inhibited T4 release. The activity
      of the benzothiazoles for disrupting thyroid hormone activity was verified in
      vivo using X. laevis tadpoles in a 7-day assay. The 2 most potent chemicals for
      TPO inhibition, MBT and CMBT, produced responses in vivo indicative of T4
      synthesis inhibition including induction of sodium iodide symporter mRNA and
      decreases in glandular and circulating thyroid hormones. The capability to
      measure thyroid hormone levels in the glands and blood by ultrahigh performance
      LC-MS/MS methods optimized for small tissue samples was critical for effects
      interpretation. These results indicate that inhibition of TPO activity in vitro
      was a good indicator of a chemical's potential for thyroid hormone disruption in
      vivo and may be useful for prioritizing chemicals for further investigation. 

PMID- 25953702
TI  - Cytotoxic Synergy Between Cytokines and NSAIDs Associated With Idiosyncratic
      Hepatotoxicity Is Driven by Mitogen-Activated Protein Kinases.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most frequent causes
      of idiosyncratic, drug-induced liver injury (IDILI). Mechanisms of IDILI are
      unknown, but immune responses are suspected to underlie them. In animal models of
      IDILI, the cytokines tumor necrosis factor-alpha (TNFalpha) and interferon-gamma
      (IFNgamma) are essential to the pathogenesis. Some drugs associated with IDILI
      interact with cytokines to kill hepatocytes in vitro, and mitogen-activated
      protein kinases (MAPKs) might play a role. We tested the hypothesis that caspases
      and MAPKs are involved in NSAID/cytokine-induced cytotoxicity. NSAIDs that are
      acetic acid (AA) derivatives and associated with IDILI synergized with TNFalpha
      in causing cytotoxicity in HepG2 cells, and IFNgamma enhanced this interaction.
      NSAIDs that are propionic acid (PA) derivatives and cause IDILI that is of less
      clinical concern also synergized with TNFalpha, but IFNgamma was without effect.
      Caspase inhibition prevented cytotoxicity from AA and PA derivative/cytokine
      treatment. Treatment with a representative AA or PA derivative induced activation
      of the MAPKs c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase
      (ERK), and p38. Inhibition of either JNK or ERK reduced cytotoxicity from
      cytokine interactions with AA derivatives. In contrast, an ERK inhibitor
      potentiated cytotoxicity from cytokine interactions with PA derivatives. An AA
      derivative but not a PA derivative enhanced IFNgamma-mediated activation of STAT
      1, and this enhancement was ERK-dependent. These findings raise the possibility
      that some IDILI reactions result from drug/cytokine synergy involving caspases
      and MAPKs and suggest that, even for drugs within the same pharmacologic class,
      synergy with cytokines occurs by different kinase signaling mechanisms. 

PMID- 25953704
TI  - Potent anti-tumor response by targeting B cell maturation antigen (BCMA) in a
      mouse model of multiple myeloma.
AB  - Multiple myeloma (MM) is an aggressive incurable plasma cell malignancy with a
      median life expectancy of less than seven years. Antibody-based therapies have
      demonstrated substantial clinical benefit for patients with hematological
      malignancies, particular in B cell Non-Hodgkin's lymphoma. The lack of
      immunotherapies specifically targeting MM cells led us to develop a human-mouse
      chimeric antibody directed against the B cell maturation antigen (BCMA), which is
      almost exclusively expressed on plasma cells and multiple myeloma cells. The high
      affinity antibody blocks the binding of the native ligands APRIL and BAFF to
      BCMA. This finding is rationalized by the high resolution crystal structure of
      the Fab fragment in complex with the extracellular domain of BCMA. Most
      importantly, the antibody effectively depletes MM cells in vitro and in vivo and
      substantially prolongs tumor-free survival under therapeutic conditions in a
      xenograft mouse model. A BCMA-antibody-based therapy is therefore a promising
      option for the effective treatment of multiple myeloma and autoimmune diseases. 

PMID- 25953706
TI  - Interaction effects in comorbid psychopathology.
AB  - PURPOSE: Comorbidity in psychopathology is the norm. Despite some initial
      evidence, few studies have examined if the presence of comorbid conditions
      changes the expression of the pathology, either through increased severity of the
      syndrome(s) or by expanding to symptoms beyond the syndrome(s) (i.e., symptom
      overextension). The following report provides an illustration of interactive
      effects and overextension in comorbid pathology. METHOD: A large pool of patients
      from a university hospital were assessed using SCID-I/P interviews. Of these, 230
      patients diagnosed with major depressive disorder, social phobia, or both were
      included in the study. RESULTS: Symptoms not belonging to either index condition
      (major depressive disorder or social phobia) reliably overextended in comorbid
      cases (odds ratios between 2.82 and 15.75). CONCLUSIONS: Current research
      methodologies (e.g., structured interviews) do not allow for the examination of
      overextended symptoms. The authors make a call for future psychopathological
      research to search systematically for interactive effects by adopting more
      inclusive or flexible assessments.

PMID- 25953705
TI  - Micro-CT Analysis of Radiation-Induced Osteopenia and Bone Hypovascularization in
      Rat.
AB  - Treatment of carcinomas of the upper aerodigestive tract often requires external
      radiation therapy. However, radiation affects all the components of bone, with
      different degrees of sensitivity, and may produce severe side effects such as
      mandibular osteoradionecrosis (ORN). Intraosseous vascularization is thought to
      be decreased after irradiation, but its impact on total bone volume is still
      controversial. The aim of this study was to compare intraosseous vascularization,
      cortical bone thickness, and total bone volume in a rat model of ORN versus
      nonirradiated rats, using a micro-computed tomography (micro-CT) analysis after
      intracardiac injection of a contrast agent. The study was performed on 8-week-old
      Lewis 1A rats (n = 14). Eleven rats underwent external irradiation on the hind
      limbs by a single 80-Gy dose. Three rats did not receive irradiation and served
      as controls for statistical analysis. Eight weeks after the external irradiation,
      all the animals received a barium sulfate intracardiac injection under general
      anesthesia. All samples were analyzed with the micro-computed tomography system
      at a resolution of 5.5 MUm. The images were later processed to create 3D
      reconstructions and study vascularization, bone volume, and cortical thickness.
      Data from irradiated and nonirradiated rats were compared using the Kruskal
      Wallis test. No animal died after irradiation. Nineteen irradiated tibias and six
      nonirradiated tibias were included for micro-CT analysis. The vessel percentage
      was significantly lower in irradiated bones (p = 0.0001). The distance between
      the vessels, a marker of vascular destruction, was higher after irradiation (p =
      0.001). The vessels were also more altered distally after irradiation (p =
      0.028). Cortical thickness was severely decreased after irradiation, sometimes
      even reduced to zero. Both trabecular and cortical structures were destroyed
      after irradiation, with wide bone gaps. Finally, both total bone volume (p =
      0.0001) and cortical thickness (p = 0.0001) were significantly decreased in
      irradiated tibias compared to nonirradiated tibias. These results led to multiple
      spontaneous fractures in the irradiated group, and the destruction of
      intraosseous vessels observed macroscopically with the radiographic preview. This
      study revealed the impact of radiation on intraosseous vasculature and cortical
      bone with a micro-CT analysis in a rat ORN model. Hypovascularization and
      osteopenia are consistent with the literature, contributing a morphological scale
      with high resolution. Visualization of the vasculature by micro-CT is an
      innovative technique to see the changes after radiation, and should help adjust
      bone tissue engineering in irradiated bone.

PMID- 25953707
TI  - Variability in Asthma Inflammatory Phenotype in Induced Sputum. Frequency and
      Causes.
AB  - INTRODUCTION: Recent studies have found variability in asthma inflammatory
      phenotypes determined by the inflammatory cells in induced sputum (IS). The aim
      of this study was to determine the frequency and factors affecting inflammatory
      phenotype variability in IS. METHODS: Retrospective observational study that
      included 61 asthmatic patients who underwent at least two IS tests over a period
      of 5 years. They were classified according to their baseline inflammatory
      phenotype and subsequently grouped according to phenotype variability (persistent
      eosinophilic, persistent non-eosinophilic and intermittent eosinophilic).
      Demographic, clinical and functional data and factors potentially influencing IS
      variability were collected in all cases. RESULTS: Of the 61 patients, 31 (50.8%)
      had a change with respect to baseline inflammatory phenotype. Of these, 16
      (51.6%) were eosinophilic, 5 (16.1%) neutrophilic, 1 (3.2%) mixed and 9 (29.1%)
      paucigranulocytic. According to phenotype variability, 18 patients (29.5%) were
      classified as persistent eosinophilic, 17 (27.9%) non-persistent eosinophilic,
      and 26 (42.6%) intermittent eosinophilic. Smoking and recent asthma exacerbation
      were significantly associated with increased risk of variability of the IS
      inflammatory phenotype (OR=6.44; p=.013; 95% CI=1.49-27.80 and OR=5.84; p=.022;
      95% CI=1.29-26.37, respectively). CONCLUSION: Half of asthma patients,
      predominantly those with eosinophilic phenotype, present a change in IS
      inflammatory phenotype. This variability is associated with smoking and recent
      asthma exacerbation. Data suggest these factors can modify the classification of
      IS inflammatory phenotype in clinical practice.

PMID- 25953708
TI  - Brotherhood of genetics and preventive medication.

PMID- 25953709
TI  - Rituximab in anti-GBM disease: A retrospective study of 8 patients.
AB  - OBJECTIVES: Anti-glomerular basement membrane (GBM) disease is a rare
      autoantibody-mediated disorder presenting as rapidly progressive
      glomerulonephritis, and often with pulmonary hemorrhage. Antibody removal with
      plasmapheresis and immunosuppressive drugs are the cornerstones of the treatment.
      Data regarding the use of specific B-cell depleting therapy such as rituximab are
      lacking. METHODS: We conducted a retrospective observational study of 8 patients
      with severe and/or refractory GBM disease that received rituximab therapy.
      RESULTS: Eight patients (2 men, 6 women) with a mean age of 26 +/- 13.1 years old
      were included. Seven had severe renal involvement [median creatinin level was 282
      MUmol/l, range (65-423)] requiring high immunosuppressive or plasmapheresis
      dependent, and two had relapse of pulmonary hemorrhage including one with renal
      failure. Patients received an initial immunosuppressive treatment including
      steroid and cyclosphosphamide (n = 8) and plasmapheresis (n = 5). Except one late
      relapse, rituximab therapy was started within two months after diagnosis. All
      patients except one received 4 weekly dose of rituximab (375 mg(2)). Anti-GBM
      antibodies were still present in 6/8 patients, at rituximab initiation. Complete
      remission was observed in 7 out of 8 patients, mostly 3 months after rituximab
      therapy. After a mean follow-up of 25.6 months (range 4-93), patient and renal
      survival were 100% and 75% respectively, but rituximab use did not improve GFR.
      Anti-GBM antibodies remained negative for all patients during follow-up. Only one
      patient developed a severe bacterial infection but no opportunistic or viral
      infections were reported. CONCLUSION: Rituximab may represent an additional
      and/or alternative therapy in the induction treatment of anti-GBM disease.

PMID- 25953710
TI  - The Guianese population of the fire ant Solenopsis saevissima is unicolonial.
AB  - In this study, conducted in French Guiana, a part of the native range of the fire
      ant Solenopsis saevissima, we compared the cuticular hydrocarbon profiles of
      media workers with previous results based on intraspecific aggressiveness tests.
      We noted a strong congruence between the two studies permitting us to delimit 2
      supercolonies extending over large distances (up to 54 km), a phenomenon known as
      unicoloniality. Solenopsis geminata workers, taken as an out-group for cluster
      analyses, have a very different cuticular hydrocarbon profile. Because S.
      saevissima has been reported outside its native range, our conclusion is that
      this species has the potential to become invasive because unicoloniality (i.e.,
      the main attribute for ants to become invasive) was shown at least for the
      Guianese population. 

PMID- 25953711
TI  - Response to a letter to the editor entitled "A Case of Leishmaniasis With Lupus
      Like Presentation".

PMID- 25953712
TI  - A case of leishmaniasis with a lupus-like presentation.

PMID- 25953713
TI  - Outcome of Budd-Chiari syndrome in Behcet's syndrome.

PMID- 25953714
TI  - 28(th) ASMBS Presidential Address: "Achieving our Vision".

PMID- 25953715
TI  - Comment on: Hospital volume and outcomes for laparoscopic gastric bypass and
      adjustable gastric banding in the modern era.

PMID- 25953716
TI  - Laparoscopic median gastrectomy for stenosis following sleeve gastrectomy.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has become an established
      primary bariatric procedure. Gastric stenosis after LSG has been reported in a
      few studies and often occurs at the level of incisura or midbody because of a
      technical operative error and could be associated with a leak. This can be
      managed by endoscopic dilations or revision surgery. The objective of this study
      is to describe a novel technique to deal with sleeve stenosis and its outcome.
      METHODS: Two patients presented with sleeve stenosis after LSG and underwent a
      novel technique. The patients were followed up for 18 months. RESULTS: We
      describe a novel technique of laparoscopic median gastrectomy in 2 patients that
      involved resection of the stenotic segment followed by a hand-sewn,
      gastrogastric, end-to-end anastomosis. Both patients had successfully recovered
      from stenosis related symptoms, although one required an endoscopic dilation of
      the anastomosis. CONCLUSION: Laparoscopic median gastrectomy is a feasible and
      effective option in patients who have failed conservative management of stenosis
      after LSG and in whom there is a desire to avoid seromyotomy or conversion to
      gastric bypass.

PMID- 25953717
TI  - Video of laparoscopic hiatal hernia repair and Roux-en-Y gastric bypass.

PMID- 25953719
TI  - Laparoscopic repair of postbariatric incarcerated diaphragmatic hernia presenting
      as large bowel obstruction.

PMID- 25953720
TI  - Intraluminal migrated adjustable gastric band after banded bypass into the
      terminal ileum: a case report of laparoscopic band removal.

PMID- 25953721
TI  - In vitro performance of implant-supported monolithic zirconia crowns: Influence
      of patient-specific tooth-coloured abutments with titanium adhesive bases.
AB  - OBJECTIVE: To investigate the influence of the combination of patient-specific
      abutments and titanium adhesive bases on the long-term in vitro performance of
      anterior crowns. METHODS: Ten systems of screw-retained implant and adhesive base
      combinations (n=8/group) were restored with zirconia or polyetherketone (PEEK)
      abutments and identical full-anatomical zirconia crowns. For simulating clinical
      anterior loading, implants were fixed at an angle of 135 degrees  and submitted
      to prolonged thermal cycling and mechanical loading (TC: 6*3000 cycles, 5 degrees
      C/55 degrees C; ML: 100N, 3.6*10(6) cycles) to cause and register fatigue
      failure. Failed restorations were examined by means of scanning electron
      microscopy. Surviving restorations were loaded to fracture. Data (mean+/-standard
      deviation) were statistically analyzed (ANOVA; Bonferroni; Kaplan-Meier-Log-Rank;
      alpha=0.05). RESULTS: Seven systems survived TCML without any failure. The other
      three systems showed loosening and fracturing of the screw (0.4-1.6*10(6)
      loadings) or debonding between base and abutment (0.002-3.4*10(6) loadings). None
      of the systems showed any fracture of the crown or failed bonding between
      abutment and crown. The Log-Rank test showed significant (p=0.000) differences.
      Fracture data significantly varied (ANOVA p=0.000) between the individual systems
      (minimum: 371N; maximum: 763N). Failures were mostly caused by bending or
      fracturing of the screw and in three cases by fracture of the abutment.
      CONCLUSIONS: Anterior implant-supported zirconia crowns on titanium adhesive
      bases and bonded patient-specific zirconia abutments provided good in vitro
      performance and high fracture resistance. Sufficient high torque moments and
      early re-screwing may be advised. CLINICAL RELEVANCE: Most adhesive base and
      abutment combinations may be appropriate for anterior application. Individual
      improvements may contribute to enduring success.

PMID- 25953722
TI  - Discovery, bioactivity and docking simulation of Vorinostat analogues containing
      1,2,4-oxadiazole moiety as potent histone deacetylase inhibitors and antitumor
      agents.
AB  - In our study, three series of hydroxamate, 2-aminobenzamide, and trifluoromethyl
      ketone analogues have been designed and synthesized. The synthesized compounds
      were investigated for their in vitro antiproliferative activities using the MTT
      based assay against three human cancer cell lines including A549, NCI-H661, and
      U937. Most analogues exhibited higher antiproliferative activities against human
      acute myeloid leukemia cell U937 than the other two human lung cancer cell lines.
      Furthermore, the compounds were examined against HDAC1, 2, and 8 isoforms.
      Docking study of compounds 6h, 9b, and 10a suggested that they might bind tightly
      to the binding pocket of HDAC2 and/or HDAC8. The results suggest that these
      compounds might have potential as lead compounds for the development of anti
      tumor drugs with HDACs inhibitory activities.

PMID- 25953723
TI  - MicroRNA-429 suppresses cell proliferation, epithelial-mesenchymal transition,
      and metastasis by direct targeting of BMI1 and E2F3 in renal cell carcinoma.
AB  - BACKGROUND: MicroRNA-429 (miR-429), a short noncoding RNA belonging to the miR
      200 superfamily, plays a crucial role in tumorigenesis and tumor progression. It
      also acts as a modulator of epithelial-to-mesenchymal transition, a cell
      development regulating process that affects tumor development and metastasis. The
      aim of this study was to investigate the potential role of miR-429 in regulating
      growth and metastasis of renal cell carcinoma. METHODS: miR-429 expression was
      stably up-regulated or down-regulated in the renal cell carcinoma ACHN and A498
      cell lines, and cell proliferation and metastasis were assessed. RESULTS: miR-429
      overexpression inhibited cell proliferation, colony formation, migration, and
      invasion. Suppression of endogenous miR-429 promoted cell growth and metastasis.
      miR-429 was shown to directly target the 3' untranslated regions of B-cell
      specific Moloney murine leukemia virus insertion site 1 (BMI1) and E2F
      transcription factor 3 (E2F3) transcripts, regulating their expression, as well
      as that of the downstream epithelial-to-mesenchymal transition markers E
      cadherin, N-cadherin, vimentin, p14, and p16. CONCLUSIONS: These results revealed
      a tumor suppressive role for miR-429 in renal cell carcinoma through directly
      targeting BMI1 and E2F3.

PMID- 25953725
TI  - Solid phase synthesis, NMR structure determination of alpha-KTx3.8, its in silico
      docking to Kv1.x potassium channels, and electrophysiological analysis provide
      insights into toxin-channel selectivity.
AB  - Animal venoms, such as those from scorpions, are a potent source for new
      pharmacological substances. In this study we have determined the structure of the
      alpha-KTx3.8 (named as Bs6) scorpion toxin by multidimensional (1)H homonuclear
      NMR spectroscopy and investigated its function by molecular dynamics (MD)
      simulations and electrophysiological measurements. Bs6 is a potent inhibitor of
      the Kv1.3 channel which plays an important role during the activation and
      proliferation of memory T-cells (TEM), which play an important role in autoimmune
      diseases. Therefore, it could be an interesting target for treatment of
      autoimmune diseases. In this study, Bs6 was synthesised by solid phase synthesis
      and its three-dimensional (3D) structure has been determined. To gain a deeper
      insight into the interaction of Bs6 with different potassium channels like hKv1.1
      and hKv1.3, the protein-protein complex was modelled based on known toxin-channel
      structures and tested for stability in MD simulations using GROMACS. The toxin
      channel interaction was further analysed by electrophysiological measurements of
      different potassium channels like hKv1.3 and hKv7.1. As potassium channel
      inhibitors could play an important role to overcome autoimmune diseases like
      multiple sclerosis and type-1 diabetes mellitus, our data contributes to the
      understanding of the molecular mechanism of action and will ultimately help to
      develop new potent inhibitors in future. 

PMID- 25953726
TI  - Single injection of basic fibroblast growth factor to treat severe vocal fold
      lesions and vocal fold paralysis.
AB  - OBJECTIVES/HYPOTHESIS: Severe vocal fold lesions such as vocal fold sulcus,
      scars, and atrophy induce a communication disorder due to severe hoarseness, but
      a treatment has not been established. Basic fibroblast growth factor (bFGF)
      therapies by either four-time repeated local injections or regenerative surgery
      for vocal fold scar and sulcus have previously been reported, and favorable
      outcomes have been observed. In this study, we modified bFGF therapy using a
      single of bFGF injection, which may potentially be used in office procedures.
      STUDY DESIGN: Retrospective chart review. METHODS: Five cases of vocal fold
      sulcus, six cases of scars, seven cases of paralysis, and 17 cases of atrophy
      were treated by a local injection of bFGF. The injection regimen involved
      injecting 50 ug of bFGF dissolved in 0.5 mL saline only once into the superficial
      lamina propria using a 23-gauge injection needle. Two months to 3 months after
      the injection, phonological outcomes were evaluated. RESULTS: The maximum
      phonation time (MPT), mean airflow rate, pitch range, speech fundamental
      frequency, jitter, and voice handicap index improved significantly after the bFGF
      injection. Furthermore, improvement in the MPT was significantly greater in
      patients with (in increasing order) vocal fold atrophy, scar, and paralysis. The
      improvement in the MPT among all patients was significantly correlated with age;
      the MPT improved more greatly in younger patients. CONCLUSIONS: Regenerative
      treatments by bFGF injection-even a single injection-effectively improve vocal
      function in vocal fold lesions. LEVEL OF EVIDENCE: 4

PMID- 25953724
TI  - Identification of microRNAs specific for epithelial cell adhesion molecule
      positive tumor cells in hepatocellular carcinoma.
AB  - Therapies that target cancer stem cells (CSCs) hold promise in eliminating cancer
      burden. However, normal stem cells are likely to be targeted owing to their
      similarities to CSCs. It is established that epithelial cell adhesion molecule
      (EpCAM) is a biomarker for normal hepatic stem cells (HpSCs), and EpCAM(+) AFP(+)
      hepatocellular carcinoma (HCC) cells have enriched hepatic CSCs. We sought to
      determine whether specific microRNAs (miRNAs) exist in hepatic CSCs that are not
      expressed in normal HpSCs. We performed a pair-wise comparison of the miRNA
      transcriptome of EpCAM(+) and corresponding EpCAM(-) cells isolated from two
      primary HCC specimens, as well as from two fetal livers and three healthy adult
      liver donors by small RNA deep sequencing. We found that miR-150, miR-155, and
      miR-223 were preferentially highly expressed in EpCAM(+) HCC cells, which was
      further validated. Their gene surrogates, identified using miRNA and messenger
      RNA profiling in a cohort of 292 HCC patients, were associated with patient
      prognosis. We further demonstrated that miR-155 was highly expressed in EpCAM(+)
      HCC cells, compared to corresponding EpCAM(-) HCC cells, fetal livers with
      enriched normal hepatic progenitors, and normal adult livers with enriched mature
      hepatocytes. Suppressing miR-155 resulted in a decreased EpCAM(+) fraction in HCC
      cells and reduced HCC cell colony formation, migration, and invasion in vitro.
      The reduced levels of identified miR-155 targets predicted the shortened overall
      survival and time to recurrence of HCC patients. CONCLUSION: miR-155 is highly
      elevated in EpCAM(+) HCC cells and might serve as a molecular target to eradicate
      the EpCAM(+) CSC population in human HCCs.

PMID- 25953727
TI  - The relationship between smoking status and health-related quality of life among
      smokers who participated in a 1-year smoking cessation programme in Taiwan: a
      cohort study using the EQ-5D.
AB  - OBJECTIVE: To assess the relationship between smoking status and health-related
      quality of life 1 year after participation in a smoking cessation programme in
      Taiwan. DESIGN: A cohort study of smokers who voluntarily participated in a
      smoking cessation programme with two follow-up assessments of smoking status via
      telephone interview, conducted 6 months and 1 year after finishing the smoking
      cessation programme. SETTING: Hospitals and clinics providing smoking cessation
      services. PARTICIPANTS: A total of 3514 participants completed both telephone
      interviews, which represents a response rate of 64%. After the interviews,
      participants were divided into four groups according to their smoking status: (1)
      long-term quitters: participants who had quit tobacco use for 1 year; (2) short
      term quitters: participants who had been smoking for at least 6 months and then
      quit tobacco for 6 months after participating in the programme; (3) relapsed
      smokers: participants who relapsed into tobacco use after ceasing tobacco use for
      6 months; and (4) continuing smokers: participants who failed to quit smoking for
      at least 1 year, despite participating in the programme. INTERVENTIONS: The
      Outpatient Smoking Cessation Service of Taiwan provides counselling and
      pharmacotherapy to individuals seeking to quit smoking. PRIMARY OUTCOMES: The
      health-related quality of life of the participants was measured using an approved
      Chinese version of the EuroQol-5D-3L (EQ-5D-3L) descriptive system. RESULTS:
      After controlling for sex, age, education, marital status, job status, monthly
      income and disease status at baseline, our results revealed that long-term
      (OR=0.61 (0.48 to 0.77)) and short-term (OR=0.65 (0.54 to 0.79)) quitters
      experienced less anxiety and depression than did continuing smokers. CONCLUSIONS:
      Our study provides evidence to support claims that all quitters, regardless of
      whether they stop smoking for 6 months or 1 year, have better quality of life
      with regard to anxiety or depression.

PMID- 25953728
TI  - Feeding infants directly at the breast during the postpartum hospital stay is
      associated with increased breastfeeding at 6 months postpartum: a prospective
      cohort study.
AB  - OBJECTIVE: To explore whether feeding only directly from the breast in the first
      24-48 h of life increases the proportion of infants receiving any breast milk at
      6 months. DESIGN: A prospective cohort study. SETTING: Three maternity hospitals
      in Melbourne, Australia. PARTICIPANTS: 1003 postpartum English-speaking women
      with a healthy singleton term infant, who intended to breast feed, were recruited
      between 2009 and 2011. Women were excluded if they or their infant were seriously
      ill. 92% (n=924) were followed up at 6 months postpartum. PRIMARY AND SECONDARY
      OUTCOME MEASURES: Main exposure variable - type of infant feeding in hospital up
      to time of study recruitment (24-48 h postpartum), categorised as 'fed directly
      at the breast only' or 'received at least some expressed breast milk (EBM) or
      infant formula'. Primary outcome - proportion of infants receiving any breast
      milk feeding at 6 months postpartum. Secondary outcomes - proportion of infants
      receiving only breast milk feeding at 6 months; breast milk feeding duration; and
      maternal characteristics associated with giving any breast milk at 6 months.
      RESULTS: Infants who had fed only at the breast prior to recruitment were more
      likely to be continuing to have any breast milk at 6 months than those who had
      received any EBM and/or infant formula (76% vs 59%; adjusted OR 1.76, 95% CI 1.24
      to 2.48 (adjusted for parity, type of birth, breastfeeding intention,
      breastfeeding problems at recruitment, public/private status, epidural for labour
      or birth, maternal body mass index and education)). CONCLUSIONS: Healthy term
      infants that fed only directly at the breast 24-48 h after birth were more likely
      to be continuing to breast feed at 6 months than those who received any EBM
      and/or formula in the early postpartum period. Support and encouragement to
      initiate breastfeeding directly at the breast is important.

PMID- 25953730
TI  - Ultrafast coherent oscillations reveal a reactive mode in the ring-opening
      reaction of fulgides.
AB  - The ultrafast ring-opening reaction of photochromic fulgides proceeds via conical
      intersections to the ground state isomers involving activation barriers in the
      excited state. The coherent oscillations observed in the femtosecond transient
      absorption signal of a methyl-substituted indolylfulgide were analysed in the
      framework of vibrational wavepackets to expose a dominant low-frequency mode at
      ~80 cm(-1). The quantum chemical calculations in the relaxed excited state
      geometry of this fulgide revealed that the experimentally observed vibrational
      normal mode has a dominant contribution to the relevant ring-opening reactive
      coordinate. 

PMID- 25953729
TI  - Keratin hydrogel carrier system for simultaneous delivery of exogenous growth
      factors and muscle progenitor cells.
AB  - Ideal material characteristics for tissue engineering or regenerative medicine
      approaches to volumetric muscle loss (VML) include the ability to deliver cells,
      growth factors, and molecules that support tissue formation from a system with a
      tunable degradation profile. Two different types of human hair-derived keratins
      were tested as options to fulfill these VML design requirements: (1) oxidatively
      extracted keratin (keratose) characterized by a lack of covalent crosslinking
      between cysteine residues, and (2) reductively extracted keratin (kerateine)
      characterized by disulfide crosslinks. Human skeletal muscle myoblasts cultured
      on coatings of both types of keratin had increased numbers of multinucleated
      cells compared to collagen or Matrigel(TM) and adhesion levels greater than
      collagen. Rheology showed elastic moduli from 10(2) to 10(5) Pa and viscous
      moduli from 10(1) to 10(4) Pa depending on gel concentration and keratin type.
      Kerateine and keratose showed differing rates of degradation due to the presence
      or absence of disulfide crosslinks, which likely contributed to observed
      differences in release profiles of several growth factors. In vivo testing in a
      subcutaneous mouse model showed that keratose hydrogels can be used to deliver
      mouse muscle progenitor cells and growth factors. Histological assessment showed
      minimal inflammatory responses and an increase in markers of muscle formation.
      (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B:
      864-879, 2016.

PMID- 25953731
TI  - Design of Fexofenadine Prodrugs Based on Tissue-Specific Esterase Activity and
      Their Dissimilar Recognition by P-Glycoprotein.
AB  - The aim of this study was to develop a suitable prodrug for fexofenadine (FXD), a
      model parent drug, that is resistant to intestinal esterase but converted to FXD
      by hepatic esterase. Carboxylesterases (CESs), human carboxylesterase 1 (hCE1)
      and human carboxylesterase 2 (hCE2), are the major esterases in human liver and
      intestine, respectively. These two CESs show quite different substrate
      specificities, and especially, hCE2 poorly hydrolyzes prodrugs with large acyl
      groups. FXD contains a carboxyl group and is poorly absorbed because of low
      membrane permeability and efflux by P-glycoprotein (P-gp). Therefore, two
      potential FXD prodrugs, ethyl-FXD and 2-hydroxyethyl-FXD, were synthesized by
      substitution of the carboxyl group in FXD. Both derivatives were resistant to
      intestinal hydrolysis, indicating their absorption as intact prodrugs. Ethyl-FXD
      was hydrolyzed by hepatic hCE1, but 2-hydroxyethyl-FXD was not. Both derivatives
      showed high membrane permeability in human P-gp-negative LLC-PK1 cells. In LLC
      GA5-COL300 cells overexpressing human P-gp, ethyl-FXD was transported by P-gp,
      but its efflux was easily saturated. Whereas 2-hydroxyethyl-FXD showed more
      efficient P-gp-mediated transport than FXD. Although the structure of 2
      hydroxyethyl-FXD only differs from ethyl-FXD by substitution of a hydroxyl group,
      2-hydroxyethyl-FXD is unsuitable as a prodrug. However, ethyl-FXD is a good
      candidate prodrug because of good intestinal absorption and hepatic conversion by
      hCE1.

PMID- 25953732
TI  - Relapse after Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic
      Syndromes: Analysis of Late Relapse Using Comparative Karyotype and Chromosome
      Genome Array Testing.
AB  - Relapse is a major cause of failure after allogeneic hematopoietic cell
      transplantation (HCT) in patients with myelodysplastic syndromes (MDS). We
      analyzed the relapse pattern in 1007 patients who underwent transplantation for
      MDS to identify factors that may determine the timing of relapse. Overall, 254
      patients relapsed: 213 before 18 months and 41 later than 18 months after HCT, a
      time point frequently used in clinical trials. The hazard of relapse declined
      progressively with time since transplantation. A higher proportion of patients
      with early relapse had high-risk cytogenetics compared with patients with late
      relapse (P = .009). Patients with late relapse had suggestively longer
      postrelapse survival than patients who relapsed early, although the difference
      was not statistically significant (P = .07). Among 41 late relapsing patients,
      sequential cytogenetic data were available in 36. In 41% of these, new clonal
      abnormalities in addition to pre-HCT findings were identified at relapse; in 30%
      pre-HCT abnormalities were replaced by new clones, in 17.3% the same clone was
      present before HCT and at relapse, and in 9.7%, no abnormalities were present
      either before HCT or at relapse. Comparative chromosomal genomic array testing in
      3 patients with late relapse showed molecular differences not detectable by
      cytogenetics between the pre-HCT clones and the clones at relapse. These data
      show that late relapses are not infrequent in patients who undergo
      transplantation for MDS. The pattern of new cytogenetic alterations at late
      relapse is similar to that observed in patients with early relapse and supports
      the concept that MDS relapse early and late after HCT is frequently due to the
      emergence of clones not detectable before HCT.

PMID- 25953734
TI  - The role of the environment in transmission of Dichelobacter nodosus between ewes
      and their lambs.
AB  - Dichelobacter nodosus (D. nodosus) is the essential causative agent of footrot in
      sheep. The current study investigated when D. nodosus was detectable on newborn
      lambs and possible routes of transmission. Specific qPCR was used to detect and
      quantify the load of D. nodosus in foot swabs of lambs at birth and 5-13 h post
      partum, and their mothers 5-13 h post-partum; and in samples of bedding, pasture,
      soil and faeces. D. nodosus was not detected on the feet of newborn lambs swabbed
      at birth, but was detected 5-13 h after birth, once they had stood on bedding
      containing naturally occurring D. nodosus. Multiple genotypes identified by
      cloning and sequencing a marker gene, pgrA, and by multi locus variable number
      tandem repeat analysis (MLVA) of community DNA from swabs on individual feet
      indicated a mixed population of D. nodosus was present on the feet of both ewes
      and lambs. There was high variation in pgrA tandem repeat number (between 3 and
      21 repeats), and multiple MLVA types. The overall similarity index between the
      populations on ewes and lambs was 0.45, indicating moderate overlap. Mother
      offspring pairs shared some alleles but not all, suggesting lambs were infected
      from sources(s) other than just their mother's feet. We hypothesise that D.
      nodosus is transferred to the feet of lambs via bedding containing naturally
      occurring populations of D. nodosus, probably as a result of transfer from the
      feet of the group of housed ewes. The results support the hypothesis that the
      environment plays a key role in the transmission of D. nodosus between ewes and
      lambs.

PMID- 25953733
TI  - Dietary salt regulates epithelial sodium channels in rat endothelial cells:
      adaptation of vasculature to salt.
AB  - BACKGROUND AND PURPOSE: The epithelial sodium channel (ENaC) is expressed in
      vascular endothelial cells and is a negative modulator of vasodilation. However,
      the role of endothelial ENaCs in salt-sensitive hypertension remains unclear.
      Here, we have investigated how endothelial ENaCs in Sprague-Dawley (SD) rats
      respond to high-salt (HS) challenge. EXPERIMENTAL APPROACH: BP and plasma
      aldosterone levels were measured. We used patch-clamp technique to record ENaC
      activity in split-open mesenteric arteries (MAs). Western blot and Griess assay
      were used to detect expression of alpha-ENaCs, eNOS and NO. Vasorelaxation in
      second-order MAs was measured with wire myograph assays. KEY RESULTS: Functional
      ENaCs were observed in endothelial cells and their activity was significantly
      decreased after 1 week of HS diet. After 3 weeks of HS diet, ENaC expression was
      also reduced. When either ENaC activity or expression was reduced, endothelium
      dependent relaxation (EDR) of MAs, in response to ACh, was enhanced. This
      enhancement of EDR was mimicked by amiloride, a blocker of ENaCs. By contrast, HS
      diet significantly increased contractility of MAs, accompanied by decreased eNOS
      activity and NO levels. However, ACh-induced release of NO was much higher in MAs
      isolated from HS rats than those from NS rats. CONCLUSIONS AND IMPLICATIONS: HS
      intake increased the BP of SD rats, but simultaneously enhanced EDR by reducing
      ENaC activity and expression due to feedback inhibition. Therefore, ENaCs may
      play an important role in endothelial cells allowing the vasculature to adapt to
      HS conditions.

PMID- 25953735
TI  - Influence of CYP2D6 and CYP2C19 genetic polymorphism on the pharmacokinetics of
      tolperisone in healthy volunteers.
AB  - PURPOSE: This is the first study that connects pharmacokinetics of tolperisone
      with genetic polymorphism of the enzymes involved in its metabolism in human. We
      aimed to identify the influence of polymorphism of two main enzymes (CYP2D6 and
      CYP2C19) on pharmacokinetic profile of parent drug. METHODS: In a single-dose
      study, 28 healthy Caucasian male volunteers received an oral dose of 150 mg of
      tolperisone. The subjects were genotyped with respect to CYP2D6 and CYP2C19
      enzymes. Plasma was sampled for up to 12 h post dose, followed by quantification
      of tolperisone by a fully validated HPLC-tandem mass spectrometry (MS/MS) method.
      The pharmacokinetic parameters were estimated using a non-compartmental method
      and compared statistically at level p < 0.05 across the genotyped groups.
      RESULTS: High variability (exceeded 100%) of main bioavailability parameters
      (AUCt, AUC(inf), C(max)) was observed in the whole group of subjects. An
      essential difference in the pharmacokinetics of tolperisone of quick metabolizers
      whose genotype expressed wild homozygote CYP2D6 *1/*1 with respect to
      heterozygous *1/*4 and *1/*5 subjects was demonstrated. The mean AUC(inf) was 2.1
      and 3.4-fold higher in *1/*4 and *1/*5, respectively, than in *1/*1 subjects. In
      case of Cmax, the differences were greater and reached maximally 3.8 times (mean
      values 54.00, 98.85, and 205.20 ng/mL for CYP2D6 *1/*1, *1/*4, and *1/*5,
      respectively). Values of the parameters for the one subject that expressed *4/*4
      genotype were even 8.5 times higher than in subjects with extensive or
      intermediate phenotype. Although CYP2C19 *1/*2 subjects had higher AUCt,
      AUC(inf), and Cmax values than *1/*1, no statistically significant differences
      were observed. Oral clearance (CL/F) significantly decreased by 65.7% in
      heterozygous *1/*2 relative to homozygous *1/*1 extensive metabolizers.
      CONCLUSION: In this study, we first demonstrated the effect of CYP2D6
      polymorphism on pharmacokinetics of tolperisone in Caucasian subjects. The
      contribution of CYP2C19 enzyme seems to be less important.

PMID- 25953736
TI  - Dose increase needed in most cystic fibrosis lung transplantation patients when
      changing from twice- to once-daily tacrolimus oral administration.
AB  - AIM: The aim of this pharmacokinetic (PK) study was to evaluate tacrolimus (TAC)
      exposure in stable cystic fibrosis (CF) lung transplant (LT) recipients,
      converted from TAC twice daily to TAC once daily in an open-label, prospective,
      single-centre study. METHODS: Eligible patients were post-transplant CF patients
      (18-65 years) with stable lung function, on stable doses of TAC twice daily and
      who were candidates to switch to TAC once daily. Twelve consecutive patients were
      included in the study. Patients had their first PK analysis on day 1, still under
      the stable TAC twice-daily regimen, and were converted to TAC once daily from day
      2 onwards. The doses were adjusted according to clinical judgement to achieve
      target levels, and a second 24-h PK period profile was obtained once the patient
      was on a stable dosage on the therapeutic range. RESULTS: The mean total (SD)
      daily dose of TAC twice daily at baseline upon enrolment was 0.17 (0.10)
      mg/kg/day. The mean (SD) daily dose of TAC once daily after adjustments was 0.22
      (0.12) mg/kg/day. In order to achieve target C min levels with a similar AUC0-24,
      82% of subjects who were converted to TAC once daily required an increase of
      dose, in a range of 0-66.7%, with a mean dose increase of 28%. CONCLUSIONS: Our
      study results indicate that the switch for conversion from TAC twice daily to TAC
      once daily in patients with CF may need dose adjustment in order to reach levels
      within the therapeutic target.

PMID- 25953737
TI  - Paraoxonase activity as a marker of exposure to xenobiotics in tobacco smoke.
AB  - The paraoxonase (PON) family is composed of 3 proteins (PON1, PON2, and PON3),
      each of which plays a crucial role in the body, displaying antioxidant, anti
      inflammatory, and antiatherosclerotic properties. The activities and properties
      of PON proteins can be modulated by a number of environmental factors, including
      cigarette smoke. In the present article, a review of existing literature is
      employed to analyze both the direct and the indirect impact of cigarette smoking
      on the activity of members of the PON family. Cigarette smoking leads to direct
      inhibition of the hydrolytic activity of PON enzymes by modification of thiol
      groups, by the reactions of free radicals, or by inhibiting enzyme-active regions
      with heavy metals. It has been shown that cigarette smoking correlates with a
      decrease in high-density lipoprotein (HDL) concentration as well as with an
      increase in other components of the lipid profile (low-density lipoprotein (LDL),
      triglycerides, and total cholesterol). By decreasing HDL levels, cigarette
      smoking likely acts indirectly to induce a decline in PON1 activity. Inhibition
      of PON1 activity by smoking is a reversible process after cessation of exposure
      to the xenobiotics in tobacco smoke. 

PMID- 25953739
TI  - Immunodetection of cocaine- and amphetamine-regulated transcript in bovine
      pancreas.
AB  - This study was aimed at identifying and determining the configuration of
      structures which contain the cocaine- and amphetamine-regulated transcript
      peptide (CART) in the bovine pancreas. The study material was collected from 20
      animals. The distribution of CART in the bovine pancreas was investigated, by an
      immunohistochemical evaluation. CART peptide in the normal pancreas has been
      identified in intrapancreatic ganglia, nerve fibres and in endocrine cells of
      Langerhans islets and exocrine pancreas. CART immunoreactive nerve fibres
      innervate the exocrine and endocrine regions and the intrapancreatic ganglia,
      where they form a moderate number of networks, encircling the cell bodies. The
      few CART-immunoreactive endocrine cells, that appear in the bovine pancreas, are
      not limited to the islet cells, where they form a subpopulation of CART
      containing cells, but are also individually distributed in the exocrine region.
      Furthermore, CART has been visualized in nerve fibres, innervating pancreatic
      outlet ducts and blood vessels. CART plays a physiological role in the integrated
      mechanisms that regulate both endocrine and exocrine pancreatic secretion. These
      results are consistent with the hypothesis that CART expression in nerve fibres
      and intrapancreatic ganglia is a common feature of the mammalian pancreas,
      whereas its expression in endocrine cells appears to be restricted to single
      cells of the bovine pancreas. 

PMID- 25953738
TI  - Functionally Structured Genomes in Lactobacillus kunkeei Colonizing the Honey
      Crop and Food Products of Honeybees and Stingless Bees.
AB  - Lactobacillus kunkeei is the most abundant bacterial species in the honey crop
      and food products of honeybees. The 16 S rRNA genes of strains isolated from
      different bee species are nearly identical in sequence and therefore inadequate
      as markers for studies of coevolutionary patterns. Here, we have compared the 1.5
      Mb genomes of ten L. kunkeei strains isolated from all recognized Apis species
      and another two strains from Meliponini species. A gene flux analysis, including
      previously sequenced Lactobacillus species as outgroups, indicated the influence
      of reductive evolution. The genome architecture is unique in that vertically
      inherited core genes are located near the terminus of replication, whereas genes
      for secreted proteins and putative host-adaptive traits are located near the
      origin of replication. We suggest that these features have resulted from a genome
      wide loss of genes, with integrations of novel genes mostly occurring in regions
      flanking the origin of replication. The phylogenetic analyses showed that the
      bacterial topology was incongruent with the host topology, and that strains of
      the same microcluster have recombined frequently across the host species
      barriers, arguing against codiversification. Multiple genotypes were recovered in
      the individual hosts and transfers of mobile elements could be demonstrated for
      strains isolated from the same host species. Unlike other bacteria with small
      genomes, short generation times and multiple rRNA operons suggest that L. kunkeei
      evolves under selection for rapid growth in its natural growth habitat. The
      results provide an extended framework for reductive genome evolution and
      functional genome organization in bacteria. 

PMID- 25953740
TI  - Apolipoprotein D subcellular distribution pattern in neuronal cells during
      oxidative stress.
AB  - Apolipoprotein D (Apo D) is a secreted glycoprotein, member of the lipocalin
      superfamily, with a related beneficial role in metabolism and lipid transport due
      to the presence of a binding pocket that allows its interaction with several
      lipids. Nowadays, it has been clearly demonstrated that Apo D expression is
      induced and its subcellular location undergoes modifications in stressful and
      pathological conditions that characterize aging processes and neurodegenerative
      diseases. The aim of the present work was to study in detail the effect of H2O2
      on the subcellular location of Apo D, in the hippocampal cell line HT22, by
      structural, ultrastructural, immunocytochemical, and molecular techniques in
      order to characterize the Apo D distribution pattern in neurons during oxidative
      stress. Our results indicate that Apo D is located in the cytoplasm under
      physiological conditions but treatment with H2O2 induces apoptosis and causes a
      displacement of Apo D location to the nucleus, coinciding with DNA fragmentation.
      In addition, we demonstrated that Apo D tends to accumulate around the nuclear
      envelope in neurons and glial cells of different brain areas in some
      neurodegenerative diseases and during human aging, but never inside the nucleus.
      These data suggest that the presence of Apo D in the nucleus, which some authors
      related with a specific transport, is a consequence of structural and functional
      alterations during oxidative stress and not the result of a specific role in the
      regulation of nuclear processes. 

PMID- 25953741
TI  - Arsenic rich Himalayan hot spring metagenomics reveal genetically novel predator
      prey genotypes.
AB  - Bdellovibrio bacteriovorus are small Deltaproteobacteria that invade, kill and
      assimilate their prey. Metagenomic assembly analysis of the microbial mats of an
      arsenic rich, hot spring was performed to describe the genotypes of the predator
      Bdellovibrio and the ecogenetically adapted taxa Enterobacter. The microbial mats
      were enriched with Bdellovibrio (1.3%) and several Gram-negative bacteria
      including Bordetella (16%), Enterobacter (6.8%), Burkholderia (4.8%),
      Acinetobacter (2.3%) and Yersinia (1%). A high-quality (47 contigs, 25X coverage;
      3.5 Mbp) draft genome of Bdellovibrio (strain ArHS; Arsenic Hot Spring) was
      reassembled, which lacked the marker gene Bd0108 associated with the usual method
      of prey interaction and invasion for this genus, while maintaining genes coding
      for the hydrolytic enzymes necessary for prey assimilation. By filtering
      microbial mat samples (< 0.45 MUm) to enrich for small predatory cell sizes, we
      observed Bdellovibrio-like cells attached side-on to E. coli through electron
      microscopy. Furthermore, a draft pan-genome of the dominant potential host taxon,
      Enterobacter cloacae ArHS (4.8 Mb), along with three of its viral genotypes (n =
      3; 42 kb, 49 kb and 50 kb), was assembled. These data were further used to
      analyse the population level evolutionary dynamics (taxonomical and functional)
      of reconstructed genotypes.

PMID- 25953742
TI  - Maternal salt and fat intake causes hypertension and sustained endothelial
      dysfunction in fetal, weanling and adult male resistance vessels.
AB  - Maternal salt and fat intake can independently programme adult cardiovascular
      status, increasing risk of cardiovascular disease in offspring. Despite its
      relevance to modern western-style dietary habits, the interaction between
      increased maternal salt and fat intake has not been examined. Female virgin
      Sprague-Dawley rats were fed, a standard control diet (CD) (10% kcal fat, 1%
      NaCl), High-fat diet (HF) (45% kcal fat, 1% NaCl), High-salt diet (SD) (10% kcal
      fat, 4% NaCl), High-fat high-salt diet (HFSD) (45% kcal fat, 4% NaCl) prior to
      pregnancy, during pregnancy and throughout lactation. Fetal, weanling and adult
      vessels were mounted on a pressure myograph at fetal day 18, weaning day 21 and
      day 135 of adulthood. Increased blood pressure in SD, HFD and HFSD male offspring
      at day 80 and 135 of age was consistent with perturbed vascular function in
      fetal, weanling and adult vessels. Maternal salt intake reduced EDHF and calcium
      mediated vasodilation, maternal fat reduced NO pathways and maternal fat and salt
      intake, a combination of the two pathways. Adult offspring cardiovascular disease
      risk may, in part, relate to vascular adaptations caused by maternal salt and/or
      fat intake during pregnancy, leading to persistent vascular dysfunction and
      sustained higher resting blood pressure throughout life. 

PMID- 25953744
TI  - Hypertrophic Cardiomyopathy in Adulthood Associated With Low Cardiovascular
      Mortality With Contemporary Management Strategies.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) has been prominently associated
      with adverse disease complications, including sudden death or heart failure death
      and a generally adverse prognosis, with annual mortality rates of up to 6%.
      OBJECTIVES: This study determined whether recent advances in management strategy,
      including implantable cardioverter-defibrillators (ICDs), heart transplantation,
      or other therapeutic measures have significantly improved survival and the
      clinical course of adult HCM patients. METHODS: We addressed long-term outcomes
      in 1,000 consecutive adult HCM patients presenting at 30 to 59 years of age (mean
      45+/-8 years) over 7.2+/-5.2 years of follow-up. RESULTS: Of 1,000 patients, 918
      (92%) survived to 53+/-9.2 years of age (range 32 to 80 years) with 91%
      experiencing no or only mild symptoms at last evaluation. HCM-related death
      occurred in 40 patients (4% [0.53%/year]) at 50+/-10 years from the following
      events: progressive heart failure (n=17); arrhythmic sudden death (SD) (n=17);
      and embolic stroke (n=2). In contrast, 56 other high-risk patients (5.6%)
      survived life-threatening events, most commonly with ICD interventions for
      ventricular tachyarrhythmias (n=33) or heart transplantation for advanced heart
      failure (n=18 [0.79%/year]). SD occurred in patients who declined ICD
      recommendations, had evaluations before application of prophylactic ICDs to HCM,
      or were without conventional risk factors. The 5- and 10-year survival rates
      (confined to HCM deaths) were 98% and 94%, respectively, not different from the
      expected all-cause mortality in the general U.S. population (p=0.25).
      Multivariate independent predictors of adverse outcome were younger age at
      diagnosis, female sex, and increased left atrial dimension. CONCLUSIONS: In a
      large longitudinally assessed adult HCM cohort, we have demonstrated that
      contemporary management strategies and treatment interventions, including ICDs
      for SD prevention, have significantly altered the clinical course, now resulting
      in a low disease-related mortality rate of 0.5%/year and an opportunity for
      extended longevity.

PMID- 25953745
TI  - The dawn of a better day for patients with hypertrophic cardiomyopathy.

PMID- 25953743
TI  - MicroRNA-125b attenuates epithelial-mesenchymal transitions and targets stem-like
      liver cancer cells through small mothers against decapentaplegic 2 and 4.
AB  - Emerging evidence suggests that epithelial-mesenchymal transitions (EMTs) play
      important roles in tumor metastasis and recurrence. Understanding molecular
      mechanisms that regulate the EMT process is crucial for improving treatment of
      hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) play important roles in HCC;
      however, the mechanisms by which miRNAs target the EMT and their therapeutic
      potential remains largely unknown. To better explore the roles of miRNAs in the
      EMT process, we established an EMT model in HCC cells by transforming growth
      factor beta 1 treatment and found that several tumor-related miRNAs were
      significantly decreased. Among these miRNAs, miR-125b expression was most
      strongly suppressed. We also found down-regulation of miR-125b in most HCC cells
      and clinical specimens, which correlated with cellular differentiation in HCC
      patients. We then demonstrated that miR-125b overexpression attenuated EMT
      phenotype in HCC cancer cells, whereas knockdown of miR-125b promoted the EMT
      phenotype in vitro and in vivo. Moreover, we found that miR-125b attenuated EMT
      associated traits, including chemoresistance, migration, and stemness in HCC
      cells, and negatively correlated with EMT and cancer stem cell (CSC) marker
      expressions in HCC specimens. miR-125b overexpression could inhibit CSC
      generation and decrease tumor incidence in the mouse xenograft model.
      Mechanistically, our data revealed that miR-125b suppressed EMT and EMT
      associated traits of HCC cells by targeting small mothers against decapentaplegic
      (SMAD)2 and 4. Most important, the therapeutic delivery of synthetic miR-125b
      mimics decreased the target molecule of CSC and inhibited metastasis in the mice
      model. These findings suggest a potential therapeutic treatment of miR-125b for
      liver cancer. CONCLUSION: miR-125b exerts inhibitory effects on EMT and EMT
      associated traits in HCC by SMAD2 and 4. Ectopic expression of miR-125b provides
      a promising strategy to treat HCC.

PMID- 25953746
TI  - The unnatural history of the ventricular septal defect: outcome up to 40 years
      after surgical closure.
AB  - BACKGROUND: Few prospective data are available regarding long-term outcomes after
      surgical closure of a ventricular septal defect (VSD). OBJECTIVES: The objective
      of this study was to investigate clinical outcomes>30 years after surgical VSD
      closure. METHODS: Patients who underwent surgical VSD closure during childhood
      between 1968 and 1980 were reexamined every 10 years. In 2012, we invited
      eligible patients to undergo another examination, which included
      electrocardiography, Holter monitoring, echocardiography, bicycle ergometry,
      measurement of N-terminal pro-B-type natriuretic peptide, and subjective health
      assessment. RESULTS: Cumulative survival was 86% at 40 years. Causes of mortality
      were arrhythmia, heart failure, endocarditis, during valvular surgery, pulmonary
      hypertension, noncardiac causes, and unknown causes. Cumulative event-free
      survival after surgery was 72% at 40 years. Symptomatic arrhythmias occurred in
      13% of patients and surgical or catheter-based reinterventions in 12%. Prevalence
      of impaired right ventricular systolic function increased from 1% in 2001 to 17%
      in 2012 (p=0.001). Left ventricular systolic function was impaired but stable in
      21% of patients. Aortic regurgitation occurred more often in the last 20 years
      (p=0.039), and mean exercise capacity decreased (p=0.003). N-terminal pro-B-type
      natriuretic peptide (median: 11.6 pmol/l [interquartile range: 7.0 to 19.8
      pmol/l]) was elevated (>14 pmol/l) in 38% of patients. A concomitant cardiac
      lesion, for example, patent ductus arteriosus, and aortic cross-clamp time were
      determinants of late events (hazard ratio: 2.84 [95% confidence interval: 1.23 to
      6.53] and hazard ratio: 1.47 per 10 min [95% confidence interval: 1.22 to 1.99],
      respectively). Patients rated their subjective health status significantly better
      than a reference population. CONCLUSIONS: Survival up to 40 years after
      successful surgical VSD closure is slightly lower than in the general Dutch
      population. Morbidity is not negligible, especially in patients with a
      concomitant cardiac lesion.

PMID- 25953747
TI  - Closure is not correction: late outcomes of ventricular septal defect surgery.

PMID- 25953748
TI  - Lack of impact of electronic health records on quality of care and outcomes for
      ischemic stroke.
AB  - BACKGROUND: Electronic health records (EHRs) may be key tools for improving the
      quality of health care, particularly for conditions for which guidelines are
      rapidly evolving and timely care is critical, such as ischemic stroke.
      OBJECTIVES: The goal of this study was to determine whether hospitals with EHRs
      differed on quality or outcome measures for ischemic stroke from those without
      EHRs. METHODS: We studied 626,473 patients from 1,236 U.S. hospitals in Get With
      the Guidelines-Stroke (GWTG-Stroke) from 2007 through 2010, linked with the
      American Hospital Association annual survey to determine the presence of EHRs. We
      conducted patient-level logistic regression analyses for each of the outcomes of
      interest. RESULTS: A total of 511 hospitals had EHRs by the end of the study
      period. Hospitals with EHRs were larger and were more often teaching hospitals
      and stroke centers. After controlling for patient and hospital characteristics,
      patients admitted to hospitals with EHRs had similar odds of receiving "all-or
      none" care (odds ratio [OR]: 1.03; 95% CI: 0.99 to 1.06; p=0.12), of discharge
      home (OR: 1.02; 95% CI: 0.99 to 1.04; p=0.15), and of in-hospital mortality (OR:
      1.01; 95% CI: 0.96 to 1.05; p=0.82). The odds of having a length of stay>4 days
      was slightly lower at hospitals with EHRs (OR: 0.97; 95% CI: 0.95 to 0.99;
      p=0.01). CONCLUSIONS: In our sample of GWTG-Stroke hospitals, EHRs were not
      associated with higher-quality care or better clinical outcomes for stroke care.
      Although EHRs may be necessary for an increasingly high-tech, transparent
      healthcare system, as currently implemented, they do not appear to be sufficient
      to improve outcomes for this important disease.

PMID- 25953749
TI  - Electronic Health Records and the Quest to Achieve the "Triple Aim".

PMID- 25953751
TI  - Avoiding the Curse of the "Sorcerer's Apprentice": How to Attract and Develop
      Successful Academicians.

PMID- 25953750
TI  - Management of pulmonary arterial hypertension.
AB  - Pulmonary hypertension (PH) is common and may result from a number of disorders,
      including left heart disease, lung disease, and chronic thromboembolic disease.
      Pulmonary arterial hypertension (PAH) is an uncommon disease characterized by
      progressive remodeling of the distal pulmonary arteries, resulting in elevated
      pulmonary vascular resistance and, eventually, in right ventricular failure. Over
      the past decades, knowledge of the basic pathobiology of PAH and its natural
      history, prognostic indicators, and therapeutic options has exploded. A thorough
      evaluation of a patient is critical to correctly characterize the PH. Cardiac
      studies, including echocardiography and right heart catheterization, are key
      elements in the assessment. Given the multitude of treatment options currently
      available for PAH, assessment of risk and response to therapy is critical in long
      term management. This review also underscores unique situations, including
      perioperative management, intensive care unit management, and pregnancy, and
      highlights the importance of collaborative care of the PAH patient through a
      multidisciplinary approach. 

PMID- 25953752
TI  - How Can a Cardiovascular Research Fellowship in the United States Affect the
      Career of a European Physician?

PMID- 25953753
TI  - Increased Numbers of Coronary Events in Winter and Spring Due to Coronary Artery
      Spasm: Effect of Age, Sex, Smoking, and Inflammation.

PMID- 25953754
TI  - Associations of Central and Peripheral Blood Pressure With Cardiac Structure and
      Function in an Adolescent Birth Cohort: The Avon Longitudinal Study of Parents
      and Children.

PMID- 25953755
TI  - The Strain, the Valve, and the LVOT Obstruction.

PMID- 25953756
TI  - Getting guidelines correct: their evidence-based recommendations for use of
      nonstatins added to statins and the need for follow-up lipid testing.

PMID- 25953757
TI  - Reply: The Strain, the Valve, and the LVOT Obstruction.

PMID- 25953758
TI  - Reply: getting guidelines correct: their evidence-based recommendations for use
      of nonstatins added to statins and the need for follow-up lipid testing.

PMID- 25953759
TI  - Beta-Blocker Variability in Treatment of Long QT Syndrome: What Is the
      Confounder?

PMID- 25953760
TI  - High-Resolution DCE-MRI of the Pituitary Gland Using Radial k-Space Acquisition
      with Compressed Sensing Reconstruction.
AB  - BACKGROUND AND PURPOSE: The pituitary gland is located outside of the blood-brain
      barrier. Dynamic T1 weighted contrast enhanced sequence is considered to be the
      gold standard to evaluate this region. However, it does not allow assessment of
      intrinsic permeability properties of the gland. Our aim was to demonstrate the
      utility of radial volumetric interpolated brain examination with the golden-angle
      radial sparse parallel technique to evaluate permeability characteristics of the
      individual components (anterior and posterior gland and the median eminence) of
      the pituitary gland and areas of differential enhancement and to optimize the
      study acquisition time. MATERIALS AND METHODS: A retrospective study was
      performed in 52 patients (group 1, 25 patients with normal pituitary glands; and
      group 2, 27 patients with a known diagnosis of microadenoma). Radial volumetric
      interpolated brain examination sequences with golden-angle radial sparse parallel
      technique were evaluated with an ROI-based method to obtain signal-time curves
      and permeability measures of individual normal structures within the pituitary
      gland and areas of differential enhancement. Statistical analyses were performed
      to assess differences in the permeability parameters of these individual regions
      and optimize the study acquisition time. RESULTS: Signal-time curves from the
      posterior pituitary gland and median eminence demonstrated a faster wash-in and
      time of maximum enhancement with a lower peak of enhancement compared with the
      anterior pituitary gland (P < .005). Time-optimization analysis demonstrated that
      120 seconds is ideal for dynamic pituitary gland evaluation. In the absence of a
      clinical history, differences in the signal-time curves allow easy distinction
      between a simple cyst and a microadenoma. CONCLUSIONS: This retrospective study
      confirms the ability of the golden-angle radial sparse parallel technique to
      evaluate the permeability characteristics of the pituitary gland and establishes
      120 seconds as the ideal acquisition time for dynamic pituitary gland imaging.

PMID- 25953761
TI  - Woven EndoBridge Intrasaccular Flow Disrupter for the Treatment of Ruptured and
      Unruptured Wide-Neck Cerebral Aneurysms: Report of 55 Cases.
AB  - BACKGROUND AND PURPOSE: The safety and efficacy of the Woven EndoBridge (WEB)
      device for the treatment of cerebral aneurysms have been investigated in several
      studies. Most of these studies focused on specific aneurysms or a certain WEB
      device. Our objective was to report the experience of 2 German centers with the
      WEB device, including technical feasibility, safety, and short-term angiographic
      outcome. MATERIALS AND METHODS: We performed a retrospective study of all
      ruptured and unruptured aneurysms that were treated with a WEB device (WEB Double
      Layer, Single-Layer, and Single-Layer Sphere) between April 2012 and August 2014.
      Primary outcome measures included the feasibility of the implantation and the
      angiographic outcome at 3-month follow-up. Secondary outcome measures included
      the clinical outcome at discharge and procedural complications. RESULTS: Fifty
      five aneurysms in 52 patients, including 14 ruptured aneurysms, underwent
      treatment with the WEB device. The median age of patients was 55 years (range, 30
      75 years); 19/55 (37%) were men. The device could be deployed in all patients and
      was implanted in 51/55 (93%) cases. Procedural complications occurred in 6/51
      (12%), comprising 2 thromboembolic events, 2 thrombus formations, 1 high-grade
      posterior cerebral artery stenosis, and 1 aneurysm rupture. None of these had
      clinical sequelae. Angiographic follow-up at 3 months was available for 44/51
      (86%) aneurysms. A favorable angiographic result at 3 months was achieved in
      29/44 (66%) cases, whereas the percentage of good anatomic results increased from
      40% in 2012 to 75% in 2014. CONCLUSIONS: The WEB device proved to be safe.
      Acceptable occlusion rates can be achieved but seem to require wide experience
      with the device.

PMID- 25953762
TI  - Diffusion Tensor Imaging and Fiber Tractography in Children with Craniosynostosis
      Syndromes.
AB  - BACKGROUND AND PURPOSE: Patients with craniosynostosis syndromes caused by
      mutations in FGFR-2, FGFR-3, and TWIST1 genes are characterized by having
      prematurely fused skull sutures and skull base synchondroses, which result in a
      skull deformity and are accompanied by brain anomalies, including altered white
      matter microarchitecture. In this study, the reliability and reproducibility of
      DTI fiber tractography was investigated in these patients. The outcomes were
      compared with those of controls. MATERIALS AND METHODS: DTI datasets were
      acquired with a 1.5T MR imaging system with 25 diffusion gradient orientations
      (voxel size = 1.8 * 1.8 * 3.0 mm(3), b-value = 1000 s/mm(2)). White matter tracts
      studied included the following: corpus callosum, cingulate gyrus, fornix,
      corticospinal tracts, and medial cerebellar peduncle. Tract pathways were
      reconstructed with ExploreDTI in 58 surgically treated patients with
      craniosynostosis syndromes and 7 controls (age range, 6-18 years). RESULTS:
      Because of the brain deformity and abnormal ventricular shape and size, DTI fiber
      tractography was challenging to perform in patients with craniosynostosis
      syndromes. To provide reliable tracts, we adapted standard tracking protocols.
      Fractional anisotropy was equal to that in controls (0.44 versus 0.45 +/- 0.02, P
      = .536), whereas mean, axial, and radial diffusivity parameters of the mean white
      matter were increased in patients with craniosynostosis syndromes (P < .001). No
      craniosynostosis syndrome-specific difference in DTI properties was seen for any
      of the fiber tracts studied in this work. CONCLUSIONS: Performing DTI fiber
      tractography in patients with craniosynostosis syndromes was difficult due to
      partial volume effects caused by an anisotropic voxel size and deformed brain
      structures. Although these patients have a normal fiber organization, increased
      diffusivity parameters suggest abnormal microstructural tissue properties of the
      investigated white matter tracts.

PMID- 25953763
TI  - Deconstructive and Reconstructive Techniques in Treatment of Vertebrobasilar
      Dissecting Aneurysms: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND AND PURPOSE: Various endovascular techniques have been applied to the
      treatment of vertebrobasilar dissecting aneurysms, including parent artery
      preservation with coiling, stent placement or flow diverter placement, and
      trapping and proximal occlusion. We performed a systematic review and meta
      analysis to study clinical and angiographic outcomes of patients undergoing
      endovascular treatment of vertebrobasilar dissecting aneurysms. MATERIALS AND
      METHODS: We performed a comprehensive literature search for studies on the
      endovascular treatment of vertebrobasilar dissecting aneurysms. From each study
      we abstracted the following data: immediate occlusion, long-term occlusion, long
      term good neurologic outcome, perioperative morbidity, perioperative mortality,
      rebleed (ruptured only), recurrence, and retreatment. We performed subgroup
      analyses of patients undergoing deconstructive-versus-reconstructive techniques.
      Meta-analysis was performed by using a random effects model. RESULTS: Seventeen
      studies with 478 patients were included in this analysis. Sixteen studies had at
      least 6 months of clinical/angiographic follow-up. Endovascular treatment was
      associated with high rates of long-term occlusion (87.0%; 95% CI, 74.0%-94.0%)
      and low recurrence (7.0%; 95% CI, 5.0%-10.0%) and retreatment rates (3.0%; 95%
      CI, 2.0%-6.0%). Long-term good neurologic outcome was 84.0% (95% CI, 65.0%
      94.0%). Deconstructive techniques were associated with higher rates of long-term
      complete occlusion compared with reconstructive techniques (88.0%; 95% CI, 35.0%
      99.0% versus 81.0%; 95% CI, 64.0%-91.0%; P < .0001). Deconstructive and
      reconstructive techniques were both associated with high rates of good neurologic
      outcome (86.0%; 95% CI, 68.0%-95.0% versus 92.0%; 95% CI, 86.0%-95.0%; P = .10).
      CONCLUSIONS: Endovascular treatment of vertebrobasilar dissecting aneurysms is
      associated with high rates of complete occlusion and good long-term neurologic
      outcomes. Deconstructive techniques are associated with higher occlusion rates.
      There was no statistical difference in neurologic outcomes between groups,
      possibly due to low power.

PMID- 25953764
TI  - Transmedullary Venous Anastomoses: Anatomy and Angiographic Visualization Using
      Flat Panel Catheter Angiotomography.
AB  - Flat panel catheter angiotomography, a recently developed angiographic technique,
      offers a spinal equivalent to the venous phase obtained during cerebral
      angiography. This report of 8 clinical cases discusses the flat panel catheter
      angiotomography appearance of a type of spinal venous structure until now
      principally known through the analysis of postmortem material, transmedullary
      venous anastomosis. The illustrated configurations include centrodorsolateral,
      median anteroposterior, median anteroposterior with duplicated origin, and
      combined centrodorsolateral/median anteroposterior transmedullary venous
      anastomoses, while a pathologic example documents the potential role of
      transmedullary venous anastomoses as collateral venous pathways. Two of the
      reported configurations have not been previously documented. Transmedullary
      venous anastomoses are normal venous structures that need to be differentiated
      from spinal cord anomalies, such as intramedullary vascular malformations. 

PMID- 25953765
TI  - Fractional killing arises from cell-to-cell variability in overcoming a caspase
      activity threshold.
AB  - When cells are exposed to death ligands such as TRAIL, a fraction undergoes
      apoptosis and a fraction survives; if surviving cells are re-exposed to TRAIL,
      fractional killing is once again observed. Therapeutic antibodies directed
      against TRAIL receptors also cause fractional killing, even at saturating
      concentrations, limiting their effectiveness. Fractional killing arises from cell
      to-cell fluctuations in protein levels (extrinsic noise), but how this results in
      a clean bifurcation between life and death remains unclear. In this paper, we
      identify a threshold in the rate and timing of initiator caspase activation that
      distinguishes cells that live from those that die; by mapping this threshold, we
      can predict fractional killing of cells exposed to natural and synthetic agonists
      alone or in combination with sensitizing drugs such as bortezomib. A
      phenomenological model of the threshold also quantifies the contributions of two
      resistance genes (c-FLIP and Bcl-2), providing new insight into the control of
      cell fate by opposing pro-death and pro-survival proteins and suggesting new
      criteria for evaluating the efficacy of therapeutic TRAIL receptor agonists. 

PMID- 25953767
TI  - Cholesterol Levels in Blood and the Risk of Prostate Cancer: A Meta-analysis of
      14 Prospective Studies.
AB  - BACKGROUND: As a neutral lipid and prominent component of the Western diet,
      cholesterol levels might be a risk factor for prostate cancer. However, current
      evidence has been inconsistent. This meta-analysis aimed to evaluate the
      association between blood cholesterol levels and the risk of prostate cancer.
      METHODS: An extensive search was performed in MEDLINE and EMBASE for prospective
      studies that have reported the association between total cholesterol (TC), high
      density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol
      (LDL) levels in blood and risk of prostate cancer. Random-effects models were
      used to summarize the study-specific results. RESULTS: Fourteen studies were
      included in this meta-analysis. In the meta-analysis, the summarized risk ratios
      (RR) for the highest to lowest cholesterol levels were as follows: 1.05 [95%
      confidence interval (CI), 0.97-1.14; P = 0.21] for TC, 0.93 (95% CI, 0.80-1.10; P
      = 0.40) for HDL, and 1.17 (95% CI, 0.88-1.55; P = 0.51) for LDL. When restricting
      to high-grade prostate cancer, the pooled RR was 1.32 (95% CI, 0.93-1.87; P =
      0.13) for TC. In dose-response analyses, a 1 mmol/L increment in blood TC, HDL,
      and LDL level conferred an RR of 1.01 (95% CI, 0.99-1.02; P = 0.38), 0.98 (95%
      CI, 0.91-1.07; P = 0.72), and 1.04 (95% CI, 0.98-1.10; P = 0.24), respectively.
      CONCLUSION: In this meta-analysis of 14 large prospective studies, blood TC, HDL,
      and LDL levels were not associated with the risk of either overall prostate
      cancer or high-grade prostate cancer. IMPACT: Our findings did not appear to
      support the hypothesis that hypercholesterolemia increases the risk of prostate
      cancer.

PMID- 25953766
TI  - Challenges and opportunities of airborne metagenomics.
AB  - Recent metagenomic studies of environments, such as marine and soil, have
      significantly enhanced our understanding of the diverse microbial communities
      living in these habitats and their essential roles in sustaining vast ecosystems.
      The increase in the number of publications related to soil and marine
      metagenomics is in sharp contrast to those of air, yet airborne microbes are
      thought to have significant impacts on many aspects of our lives from their
      potential roles in atmospheric events such as cloud formation, precipitation, and
      atmospheric chemistry to their major impact on human health. In this review, we
      will discuss the current progress in airborne metagenomics, with a special focus
      on exploring the challenges and opportunities of undertaking such studies. The
      main challenges of conducting metagenomic studies of airborne microbes are as
      follows: 1) Low density of microorganisms in the air, 2) efficient retrieval of
      microorganisms from the air, 3) variability in airborne microbial community
      composition, 4) the lack of standardized protocols and methodologies, and 5) DNA
      sequencing and bioinformatics-related challenges. Overcoming these challenges
      could provide the groundwork for comprehensive analysis of airborne microbes and
      their potential impact on the atmosphere, global climate, and our health.
      Metagenomic studies offer a unique opportunity to examine viral and bacterial
      diversity in the air and monitor their spread locally or across the globe,
      including threats from pathogenic microorganisms. Airborne metagenomic studies
      could also lead to discoveries of novel genes and metabolic pathways relevant to
      meteorological and industrial applications, environmental bioremediation, and
      biogeochemical cycles. 

PMID- 25953769
TI  - Genetic Variability Under the Seedbank Coalescent.
AB  - We analyze patterns of genetic variability of populations in the presence of a
      large seedbank with the help of a new coalescent structure called the seedbank
      coalescent. This ancestral process appears naturally as a scaling limit of the
      genealogy of large populations that sustain seedbanks, if the seedbank size and
      individual dormancy times are of the same order as those of the active
      population. Mutations appear as Poisson processes on the active lineages and
      potentially at reduced rate also on the dormant lineages. The presence of
      "dormant" lineages leads to qualitatively altered times to the most recent common
      ancestor and nonclassical patterns of genetic diversity. To illustrate this we
      provide a Wright-Fisher model with a seedbank component and mutation, motivated
      from recent models of microbial dormancy, whose genealogy can be described by the
      seedbank coalescent. Based on our coalescent model, we derive recursions for the
      expectation and variance of the time to most recent common ancestor, number of
      segregating sites, pairwise differences, and singletons. Estimates (obtained by
      simulations) of the distributions of commonly employed distance statistics, in
      the presence and absence of a seedbank, are compared. The effect of a seedbank on
      the expected site-frequency spectrum is also investigated using simulations. Our
      results indicate that the presence of a large seedbank considerably alters the
      distribution of some distance statistics, as well as the site-frequency spectrum.
      Thus, one should be able to detect from genetic data the presence of a large
      seedbank in natural populations. 

PMID- 25953768
TI  - Functional Variants in Notch Pathway Genes NCOR2, NCSTN, and MAML2 Predict
      Survival of Patients with Cutaneous Melanoma.
AB  - BACKGROUND: The Notch signaling pathway is constitutively activated in human
      cutaneous melanoma to promote growth and aggressive metastatic potential of
      primary melanoma cells. Therefore, genetic variants in Notch pathway genes may
      affect the prognosis of cutaneous melanoma patients. METHODS: We identified 6,256
      SNPs in 48 Notch genes in 858 cutaneous melanoma patients included in a
      previously published cutaneous melanoma genome-wide association study dataset.
      Multivariate and stepwise Cox proportional hazards regression and false-positive
      report probability corrections were performed to evaluate associations between
      putative functional SNPs and cutaneous melanoma disease-specific survival.
      Receiver operating characteristic curve was constructed, and area under the curve
      was used to assess the classification performance of the model. RESULTS: Four
      putative functional SNPs of Notch pathway genes had independent and joint
      predictive roles in survival of cutaneous melanoma patients. The most significant
      variant was NCOR2 rs2342924 T>C (adjusted HR, 2.71; 95% confidence interval, 1.73
      4.23; Ptrend = 9.62 * 10(-7)), followed by NCSTN rs1124379 G>A, NCOR2 rs10846684
      G>A, and MAML2 rs7953425 G>A (Ptrend = 0.005, 0.005, and 0.013, respectively).
      The receiver operating characteristic analysis revealed that area under the curve
      was significantly increased after adding the combined unfavorable genotype score
      to the model containing the known clinicopathologic factors. CONCLUSIONS: Our
      results suggest that SNPs in Notch pathway genes may be predictors of cutaneous
      melanoma disease-specific survival. IMPACT: Our discovery offers a translational
      potential for using genetic variants in Notch pathway genes as a genotype score
      of biomarkers for developing an improved prognostic assessment and personalized
      management of cutaneous melanoma patients.

PMID- 25953770
TI  - Dissociating Parieto-Frontal Networks for Phonological and Semantic Word
      Decisions: A Condition-and-Perturb TMS Study.
AB  - Left posterior inferior frontal gyrus (pIFG) and supramarginal gyrus (SMG) are
      key regions for phonological decisions, whereas angular gyrus (ANG) and anterior
      IFG (aIFG) are associated with semantics. However, it is less clear whether the
      functional contribution of one area changes in the presence of a dysfunctional
      area within the network. Using repetitive transcranial magnetic stimulation
      (rTMS), we first tested whether perturbing one area would disrupt behavior.
      Second, we applied a condition-and-perturb approach, combining parietal offline
      rTMS with frontal online rTMS to investigate how the functional contribution of a
      frontal region changes in the presence of a dysfunctional parietal region. We
      found that rTMS over SMG or pIFG delayed phonological decisions, but this was not
      enhanced by combining supramarginal rTMS with pIFG rTMS. In contrast, semantic
      decisions were only impaired when angular rTMS was combined with aIFG rTMS. We
      infer that offline rTMS caused a dysfunction of ANG which increased the
      functional relevance of aIFG for semantic decisions and sensitized this network
      to the disruptive effects of aIFG rTMS. The results provide causal evidence that
      ANG and aIFG contribute to semantics and that the functional significance of one
      area within this network depends on the functional integrity of the other.

PMID- 25953771
TI  - Parent artery occlusion for ruptured "true" posterior communicating artery
      aneurysm.
AB  - A case of a patient with a ruptured true posterior communicating artery (PCoA)
      aneurysm is reported, who had been managed by early endovascular parent artery
      occlusion with coils. The small blister aneurysm was located at the proximal PCoA
      itself and directed superiorly. Postoperative course was uneventful. During 1
      month follow-up, the patient recovered well and could care for herself. Aneurysms
      of the PCoA itself are very rare. As reported to date, surgical procedures would
      favor microsurgical clipping over endovascular coil embolization. Endovascular
      treatment may be a good alternative to surgical trapping for true PCoA blister
      aneurysm. 

PMID- 25953772
TI  - Clinical and angiographic outcomes of stent-assisted coiling of intracranial
      aneurysms.
AB  - BACKGROUND: Despite the increasing use of stent-assisted coiling (SAC), data on
      its long-term clinical and angiographic results are limited. OBJECTIVE: The
      objective of this article is to assess the long-term clinical and angiographic
      outcomes in SAC in our single-center practice. METHODS: We conducted a
      retrospective analysis of intracranial aneurysms treated with detachable coils
      during the period 2003-2012. Patients were divided into SAC and non-SAC groups
      and were analyzed for aneurysm occlusion, major recurrence and clinical outcome.
      Logistic regression analyses identified factors associated with
      clinical/angiographic outcomes (p value <0.05 was statistically significant).
      RESULTS: A total of 516 procedures met inclusion criteria: Sixty-three (12.2%)
      patients underwent SAC, of whom 56 (89%) had an elective procedure whereas 286
      (63.1%) aneurysms from the non-SAC group were ruptured. In the unruptured
      subcohort, baseline class I was achieved in 24 (38%, p = 0.91), and predischarge
      modified Rankin scale score (mRS) 0-2 was obtained in 96.4% of cases in the SAC
      group versus 90.4% in the non-stent group. The major recurrence was 9.5% versus
      11.3% in the SAC and non-SAC group, respectively (p = 0.003). At last clinical
      assessment, 98.2% of the patients from the unruptured SAC group had mRS 0-2 (mean
      follow-up, 58 months) versus 93.6% (mean follow-up, 56 months) in the unruptured
      non-SAC group (p = 0.64). Periprocedural vasospasm was associated with long-term
      poor outcome in the unruptured SAC subcohort (p = 0.0008). CONCLUSIONS: SAC and
      non-SCA techniques show comparable safety and clinical outcome. The SAC technique
      significantly decreases retreatment rates. Periprocedural vasospasm resulting
      from vessel manipulation is associated with poor outcome in SAC of unruptured
      aneurysms.

PMID- 25953773
TI  - TransForm occlusion balloon catheter for the treatment of intracranial aneurysms,
      initial experience.
AB  - INTRODUCTION: The technique of balloon remodeling allows the endovascular
      treatment of wide-neck intracranial aneurysms. For many years the only available
      devices were the Hyperform and the Hyperglide balloon catheters. Recently, other
      companies have developed newer devices, single or dual-lumen. We present our
      initial experience with the TransForm occlusion balloon catheter for the
      treatment of intracranial aneurysms. METHODS: We retrospectively analysed from
      our prospectively gathered aneurysm database all aneurysms that were treated with
      balloon remodelling using TransForm occlusion balloon catheters from January 2013
      to February 2014. We assessed patient demographics, morphological features of the
      aneurysms, procedure feasibility, technical and clinical complications. RESULTS:
      Thirty-three patients harbouring 36 intracranial saccular aneurysms were treated
      during 33 procedures. Clinical finding were: 15 incidental discovery, 13
      subarachnoid haemorrhage (SAH), five aneurysms with mass effect, one ruptured
      aneurysm with SAH and mass effect, one recanalisation and one intraparenchymal
      haematoma. Thirty-five aneurysms were in the anterior and one in the posterior
      circulation. Mean dome and neck size were, respectively, 5.8 mm and 3.6 mm.
      Twenty-three aneurysms were treated with TransForm C and 13 with TransForm SC. We
      had two procedural thromboembolic complications, without permanent clinical
      events. No early rebleeding occurred. CONCLUSIONS: In our small series, the
      TransForm occlusion balloon catheter seems to be safe and effective for the
      treatment of intracranial aneurysms, in ruptured and unruptured cases.

PMID- 25953774
TI  - MR susceptibility artefact associated with the use of Barricade coils for
      treatment of intracranial aneurysms.
AB  - Magnetic resonance angiography (MRA) is commonly used to follow up patients after
      endovascular treatment for intracranial aneurysms. Magnetic resonance artefacts
      from coil constructs may impair image quality and jeopardise the evaluation of
      the effectiveness of treatment and review of adjacent vasculature. We present
      here a technical note on the usage of Barricade coils recently introduced at our
      institution. The MRA artefacts associated with these coils may make it impossible
      to ascertain aneurysm closure and anatomy. Hence these patients would need to be
      recalled for digital subtraction angiograms for a complete neuroradiological
      follow-up. 

PMID- 25953775
TI  - Regulatory Effects of Ca2+ and H+ on the Rat Chorda Tympani Response to NaCl and
      KCl.
AB  - Modulatory effects of pHi and [Ca(2+)]i on taste receptor cell (TRC) epithelial
      sodium channel (ENaC) were investigated by monitoring chorda tympani (CT)
      responses to NaCl and KCl at various lingual voltages, before and after lingual
      application of ionomycin and with 0-10mM CaCl2 in the stimulus and rinse
      solutions adjusted to pHo 2.0-9.7. 0.1 and 0.5M KCl responses varied continuously
      with voltage and were fitted to an apical ion channel kinetic model using the
      same parameters. ENaC-dependent NaCl CT response was fitted to the same channel
      model but with parameters characteristic of ENaC. A graded increase in TRC
      [Ca(2+)]i decreased the ENaC-dependent NaCl CT response, and inhibited and
      ultimately eliminated its pH sensitivity. CT responses to KCl were pHi- and
      [Ca(2+)]i-independent. Between +/-60 mV applied lingual potential, the data were
      well described by a linear approximation to the nonlinear channel equation and
      yielded 2 parameters, the open-circuit response and the negative of the slope of
      the line in the CT response versus voltage plot, designated the response
      conductance. The ENaC-dependent NaCl CT response conductance was a linear
      function of the open-circuit response for all pHi-[Ca(2+)]i combinations
      examined. Analysis of these data shows that pHi and [Ca(2+)]i regulate TRC ENaC
      exclusively through modulation of the maximum CT response. 

PMID- 25953776
TI  - Surviving, healing and moving forward: Journeys towards resilience among Canadian
      Cree adults.
AB  - BACKGROUND: Canadian First Nations (FN) people have experienced and continue to
      experience significant adversities, yet many demonstrate aspects of resilience.
      AIM: The aim of this qualitative study was to specifically understand Cree
      adults' meanings and mechanisms of resilience following maltreatment. METHODS:
      Ten Cree adults were interviewed individually. Modified grounded theory was used
      to interpret the transcribed interviews. RESULTS: Participants discussed
      resilience as a journey of 'survival' and 'overcoming' and pathways to healing
      that were multifactorial and included traditional teachings. CONCLUSION: Mental
      health providers should consider and incorporate these mechanisms into treatment
      for Cree people, when appropriate, to aid recovery.

PMID- 25953777
TI  - The role of tau in the pathological process and clinical expression of
      Huntington's disease.
AB  - Huntington's disease is a neurodegenerative disorder caused by an abnormal CAG
      repeat expansion within exon 1 of the huntingtin gene HTT. While several genetic
      modifiers, distinct from the Huntington's disease locus itself, have been
      identified as being linked to the clinical expression and progression of
      Huntington's disease, the exact molecular mechanisms driving its pathogenic
      cascade and clinical features, especially the dementia, are not fully understood.
      Recently the microtubule associated protein tau, MAPT, which is associated with
      several neurodegenerative disorders, has been implicated in Huntington's disease.
      We explored this association in more detail at the neuropathological, genetic and
      clinical level. We first investigated tau pathology by looking for the presence
      of hyperphosphorylated tau aggregates, co-localization of tau with mutant HTT and
      its oligomeric intermediates in post-mortem brain samples from patients with
      Huntington's disease (n = 16) compared to cases with a known tauopathy and
      healthy controls. Next, we undertook a genotype-phenotype analysis of a large
      cohort of patients with Huntington's disease (n = 960) with a particular focus on
      cognitive decline. We report not only on the tau pathology in the Huntington's
      disease brain but also the association between genetic variation in tau gene and
      the clinical expression and progression of the disease. We found extensive
      pathological inclusions containing abnormally phosphorylated tau protein that co
      localized in some instances with mutant HTT. We confirmed this related to the
      disease process rather than age, by showing it is also present in two patients
      with young-onset Huntington's disease (26 and 40 years old at death). In addition
      we demonstrate that tau oligomers (suggested to be the most likely neurotoxic tau
      entity) are present in the Huntington's disease brains. Finally we highlight the
      clinical significance of this pathology by demonstrating that the MAPT haplotypes
      affect the rate of cognitive decline in a large cohort of patients with
      Huntington's disease. Our findings therefore highlight a novel important role of
      tau in the pathogenic process and clinical expression of Huntington's disease,
      which in turn opens up new therapeutic avenues for this incurable condition. 

PMID- 25953779
TI  - Reply: Is CHCHD10 Pro34Ser pathogenic for frontotemporal dementia and amyotrophic
      lateral sclerosis?

PMID- 25953778
TI  - Existing Pittsburgh Compound-B positron emission tomography thresholds are too
      high: statistical and pathological evaluation.
AB  - Amyloid-beta, a hallmark of Alzheimer's disease, begins accumulating up to two
      decades before the onset of dementia, and can be detected in vivo applying
      amyloid-beta positron emission tomography tracers such as carbon-11-labelled
      Pittsburgh compound-B. A variety of thresholds have been applied in the
      literature to define Pittsburgh compound-B positron emission tomography
      positivity, but the ability of these thresholds to detect early amyloid-beta
      deposition is unknown, and validation studies comparing Pittsburgh compound-B
      thresholds to post-mortem amyloid burden are lacking. In this study we first
      derived thresholds for amyloid positron emission tomography positivity using
      Pittsburgh compound-B positron emission tomography in 154 cognitively normal
      older adults with four complementary approaches: (i) reference values from a
      young control group aged between 20 and 30 years; (ii) a Gaussian mixture model
      that assigned each subject a probability of being amyloid-beta-positive or
      amyloid-beta-negative based on Pittsburgh compound-B index uptake; (iii) a k
      means cluster approach that clustered subjects into amyloid-beta-positive or
      amyloid-beta-negative based on Pittsburgh compound-B uptake in different brain
      regions (features); and (iv) an iterative voxel-based analysis that further
      explored the spatial pattern of early amyloid-beta positron emission tomography
      signal. Next, we tested the sensitivity and specificity of the derived thresholds
      in 50 individuals who underwent Pittsburgh compound-B positron emission
      tomography during life and brain autopsy (mean time positron emission tomography
      to autopsy 3.1 +/- 1.8 years). Amyloid at autopsy was classified using Consortium
      to Establish a Registry for Alzheimer's Disease (CERAD) criteria, unadjusted for
      age. The analytic approaches yielded low thresholds (standard uptake value
      ratiolow = 1.21, distribution volume ratiolow = 1.08) that represent the earliest
      detectable Pittsburgh compound-B signal, as well as high thresholds (standard
      uptake value ratiohigh = 1.40, distribution volume ratiohigh = 1.20) that are
      more conservative in defining Pittsburgh compound-B positron emission tomography
      positivity. In voxel-wise contrasts, elevated Pittsburgh compound-B retention was
      first noted in the medial frontal cortex, then the precuneus, lateral frontal and
      parietal lobes, and finally the lateral temporal lobe. When compared to post
      mortem amyloid burden, low proposed thresholds were more sensitive than high
      thresholds (sensitivities: distribution volume ratiolow 81.0%, standard uptake
      value ratiolow 83.3%; distribution volume ratiohigh 61.9%, standard uptake value
      ratiohigh 62.5%) for CERAD moderate-to-frequent neuritic plaques, with similar
      specificity (distribution volume ratiolow 95.8%; standard uptake value ratiolow,
      distribution volume ratiohigh and standard uptake value ratiohigh 100.0%). A
      receiver operator characteristic analysis identified optimal distribution volume
      ratio (1.06) and standard uptake value ratio (1.20) thresholds that were nearly
      identical to the a priori distribution volume ratiolow and standard uptake value
      ratiolow. In summary, we found that frequently applied thresholds for Pittsburgh
      compound-B positivity (typically at or above distribution volume ratiohigh and
      standard uptake value ratiohigh) are overly stringent in defining amyloid
      positivity. Lower thresholds in this study resulted in higher sensitivity while
      not compromising specificity. 

PMID- 25953780
TI  - Is CHCHD10 Pro34Ser pathogenic for frontotemporal dementia and amyotrophic
      lateral sclerosis?

PMID- 25953781
TI  - A Sensitive Dilute-and-Shoot Approach for the Simultaneous Screening of 71
      Stimulants and 7 Metabolites in Human Urine by LC-MS-MS with Dynamic MRM.
AB  - A novel, reliable and sensitive liquid chromatography-tandem mass spectrometry
      (LC-MS-MS) method was developed with dynamic multiple reaction monitoring (dMRM)
      mode for the simultaneous screening of 71 stimulants and 7 metabolites in human
      urine using unsophisticated MS instruments (Agilent triple-quadruple 6410 B mass
      spectrometer). With a known retention time of an analyte, dMRM algorithm monitors
      each MRM transition only around its expected retention time. Therefore, dMRM
      enables the maximization of dwell times and provides much higher sensitivity and
      reproducibility than the conventional multiple reaction monitoring mode (cMRM).
      After precipitation of protein, the urine sample was injected into LC-MS-MS
      system directly without sample pre-concentration. For comparison, cMRM and dMRM
      acquisitions were performed under the same chromatographic conditions. The result
      showed that the signal response and quality of the chromatograms for each
      stimulant improved significantly with dMRM over cMRM. The method has been fully
      validated giving limits of detection (0.1-25 ng/mL) satisfactory for its
      application to anti-doping analysis. The repeatability of the concentrations and
      the retention times are good both for intra- and for inter-day experiments (%CV
      of concentrations always <20 and %CV of retention times <0.5). The method also
      afforded satisfactory results in terms of accuracy, matrix effect and
      specificity. 

PMID- 25953782
TI  - Exploring possible epigenetic mediation of early-life environmental exposures on
      adiposity and obesity development.

PMID- 25953784
TI  - Mendelian randomization studies: a review of the approaches used and the quality
      of reporting.
AB  - BACKGROUND: Mendelian randomization (MR) studies investigate the effect of
      genetic variation in levels of an exposure on an outcome, thereby using genetic
      variation as an instrumental variable (IV). We provide a meta-epidemiological
      overview of the methodological approaches used in MR studies, and evaluate the
      discussion of MR assumptions and reporting of statistical methods. METHODS: We
      searched PubMed, Medline, Embase and Web of Science for MR studies up to December
      2013. We assessed (i) the MR approach used; (ii) whether the plausibility of MR
      assumptions was discussed; and (iii) whether the statistical methods used were
      reported adequately. RESULTS: Of 99 studies using data from one study population,
      32 used genetic information as a proxy for the exposure without further
      estimation, 44 performed a formal IV analysis, 7 compared the observed with the
      expected genotype-outcome association, and 1 used both the latter two approaches.
      The 80 studies using data from multiple study populations used many different
      approaches to combine the data; 52 of these studies used some form of IV
      analysis; 44% of studies discussed the plausibility of all three MR assumptions
      in their study. Statistical methods used for IV analysis were insufficiently
      described in 14% of studies. CONCLUSIONS: Most MR studies either use the genotype
      as a proxy for exposure without further estimation or perform an IV analysis. The
      discussion of underlying assumptions and reporting of statistical methods for IV
      analysis are frequently insufficient. Studies using data from multiple study
      populations are further complicated by the combination of data or estimates. We
      provide a checklist for the reporting of MR studies.

PMID- 25953785
TI  - Cohort Profile: The Australian Parental Supply of Alcohol Longitudinal Study
      (APSALS).
AB  - The Australian Parental Supply of Alcohol Longitudinal Study (APSALS) was
      established in 2010 to investigate the short- and long-term associations between
      exposure to early parental alcohol provision, early adolescent alcohol
      initiation, subsequent alcohol use and alcohol-related harms, controlling for a
      wide range of parental, child, familial, peer and contextual covariates. The
      cohort commenced with 1927 parent-child dyads comprising Australian Grade 7
      school students (mean age = 12.9 years, range = 10.8-15.7 years), and a
      parent/guardian. Baseline, 1- and 2-year follow-up data have been collected, with
      > 90% retention, and a 3-year follow-up is under way. The data collected include
      child, familial, parental and peer factors addressing demographics, alcohol use
      and supply, parenting practices, other substance use, adolescent behaviours and
      peer influences. The cohort is ideal for prospectively examining predictors of
      initiation and progression of alcohol use, which increases markedly through
      adolescence.

PMID- 25953783
TI  - A genome-wide association study of body mass index across early life and
      childhood.
AB  - BACKGROUND: Several studies have investigated the effect of known adult body mass
      index (BMI) associated single nucleotide polymorphisms (SNPs) on BMI in
      childhood. There has been no genome-wide association study (GWAS) of BMI
      trajectories over childhood. METHODS: We conducted a GWAS meta-analysis of BMI
      trajectories from 1 to 17 years of age in 9377 children (77,967 measurements)
      from the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Western
      Australian Pregnancy Cohort (Raine) Study. Genome-wide significant loci were
      examined in a further 3918 individuals (48,530 measurements) from Northern
      Finland. Linear mixed effects models with smoothing splines were used in each
      cohort for longitudinal modelling of BMI. RESULTS: A novel SNP, downstream from
      the FAM120AOS gene on chromosome 9, was detected in the meta-analysis of ALSPAC
      and Raine. This association was driven by a difference in BMI at 8 years (T
      allele of rs944990 increased BMI; PSNP = 1.52 * 10(-8)), with a modest
      association with change in BMI over time (PWald(Change) = 0.006). Three known
      adult BMI-associated loci (FTO, MC4R and ADCY3) and one childhood obesity locus
      (OLFM4) reached genome-wide significance (PWald < 1.13 * 10(-8)) with BMI at 8
      years and/or change over time. CONCLUSIONS: This GWAS of BMI trajectories over
      childhood identified a novel locus that warrants further investigation. We also
      observed genome-wide significance with previously established obesity loci,
      making the novel observation that these loci affected both the level and the rate
      of change in BMI. We have demonstrated that the use of repeated measures data can
      increase power to allow detection of genetic loci with smaller sample sizes.

PMID- 25953786
TI  - Incremental predictive value of 152 single nucleotide polymorphisms in the 10
      year risk prediction of incident coronary heart disease: the Rotterdam Study.
AB  - OBJECTIVE: To examine the incremental predictive value of genetic risk scores of
      coronary heart disease (CHD) in the 10-year risk prediction of incident CHD.
      METHODS: In 5899 subjects, we used 152 single nucleotide polymorphisms (SNPs)
      associated with coronary artery disease by the CARDIoGRAMplusC4D consortium to
      construct three weighted genetic risk scores: (i) GRS(gws) based on 49 genome
      wide significant SNPs; (ii) GRS(fdr) based on 103 suggestively associated SNPs;
      and (iii) GRS(all) based on all 152 SNPs. We examined the changes in
      discrimination and reclassification of incident CHD when adding the genetic risk
      scores to models including traditional risk factors. We repeated the analysis for
      prevalent CHD. RESULTS: The genetic risk scores were associated with incident CHD
      despite adjustment for traditional risk factors and family history: participants
      had a 13% higher rate of CHD per standard deviation increase in GRS(all). GRS(all
      )improved the C-statistic by 0.006 [95% confidence interval (CI): 0.000, 0.013]
      beyond age and sex, 0.003 (95% CI: -0.001, 0.008) beyond traditional risk factors
      and 0.003 (95% CI: -0.001, 0.007) beyond traditional risk factors and family
      history. The genetic risk scores did not improve reclassification. GRS(all)
      strongly improved both discrimination and reclassification of prevalent CHD, even
      beyond traditional risk factors and family history, with a C-statistic
      improvement of 0.009 (0.003, 0.015). CONCLUSIONS: Although the genetic risk
      scores based on 152 SNPs were associated with incident CHD, they did not improve
      risk prediction. This discrepancy may be the result of SNP discovery for
      prevalent rather than incident CHD, since the SNPs do improve prediction for
      prevalent disease.

PMID- 25953787
TI  - The influence of thoron on instruments measuring radon activity concentration.
AB  - Thoron, the isotope 220 of radon, is a radionuclide whose concentration may
      influence the measurement of the activity concentration of (222)Rn in the air. If
      in the case of continuous and active sampling measuring instruments, using a pump
      for example, the influence of thoron on radon measurement is obvious and is taken
      into account in the apparatus, it is often assumed that in the case of a passive
      sampling, by diffusion through a filter for example, this thoron influence is
      negligible. This is due to the very short radioactive half-life of thoron, 55.6 s
      (3.82 d for (222)Rn), and the assumption that the diffusion time of thoron in the
      detection chamber is long enough beside that of the thoron half-life. The
      objective of this study is to check whether this assumption is true or not for
      different kinds of commercial electronic apparatus used to measure radon activity
      concentration from soil to dwellings. First of all, the devices were calibrated
      in activity concentration of radon, and then they were exposed to a controlled
      thoron atmosphere. The experiments concerning the thoron aimed to investigate the
      sensitivity to thoron in the radon measuring mode of the apparatus. Results of
      these experiments show that all devices have a very quick answer to thoron
      atmosphere, even though the sensitivities vary from one instrument to another.
      Results clearly show that this influence on radon measurement due to the thoron
      is observed also after the exposition because of the decay of (212)Pb and its
      progenies. In conclusion, the sensitivity to thoron in the radon measuring mode
      depends strongly on the type of instruments. The results of the present
      investigation show that for some apparatus, the influence of thoron cannot be
      disregarded especially when measuring radon in soil. 

PMID- 25953788
TI  - Nanodosimetry and RBE values in radiotherapy.
AB  - In a recent paper, the authors reported that the dose mean lineal energy,
      [Formula: see text] in a volume of about 10-15 nm is approximately proportional
      to the alpha-parameter in the linear-quadratic relation used in fractionated
      radiotherapy in both low- and high-LET beams. This was concluded after analyses
      of reported radiation weighting factors, WisoE (clinical RBE values), and
      [Formula: see text] values in a large range of volumes. Usually, microdosimetry
      measurements in the nanometer range are difficult; therefore, model calculations
      become necessary. In this paper, the authors discuss the calculation method. A
      combination of condensed history Monte Carlo and track structure techniques for
      calculation of mean lineal energy values turned out to be quite useful. Briefly,
      the method consists in weighting the relative dose fractions of the primary and
      secondary charged particles with their respective energy-dependent dose mean
      lineal energies. The latter were obtained using a large database of Monte Carlo
      track structure calculations. 

PMID- 25953789
TI  - Cross sections for track structure codes: volume versus surface transport.
AB  - Cross-section calculations and transport models for Monte Carlo track structure
      codes are discussed as well as the simulation of secondary electron emission
      yields from thin metal foils. Inelastic cross sections for volume (bulk) and
      surface transport of electrons in copper are presented and implemented into
      PARTRAC. Simulations for the volume and surface excitation model are presented
      and analysed. 

PMID- 25953790
TI  - Application of a CZT detector to in situ environmental radioactivity measurement
      in the Fukushima area.
AB  - Instead of conventional Ge semiconductor detectors and NaI(Tl) scintillation
      spectrometers, an application of a CdZnTe semiconductor (CZT) whose crystal has
      the dimension of 1 cm cubic to the in situ environmental radioactivity
      measurement was attempted in deeply affected areas in Fukushima region. Results
      of deposition density on soil for (134)Cs/(137)Cs obtained seemed consistent,
      comparing obtained results with those measured by the Japanese government. 

PMID- 25953791
TI  - Extreme variations of air dose rates in east Fukushima.
AB  - This report analyses the data of air (ambient) dose rates measured at 164 points
      in eastern Fukushima during a period of half a year after 10 June 2011. It is
      found that at some locations the values decreased or increased extraordinarily
      although on average the overall dose rates decreased significantly faster than
      the theoretically predicted rate. Among them the nine most extreme points are
      selected and analysed. It is found that behind these extraordinary behaviours of
      air dose rates there exists the combination of wind/rain and artificial
      structures such as sloped pavements. 

PMID- 25953792
TI  - Collaboration of local governments and experts responding to the increase of the
      environmental radiation level secondary to the nuclear accident: a unique
      activity to relieve residents' anxiety.
AB  - After the Fukushima nuclear power plant accident, 'hot spots' were found in
      Tokatsu area in Chiba prefecture. Although ambient radiation dose in this area
      was too low to harm residents' health, local residents were particularly worried
      about possible adverse effects from exposure to radiation. To avoid unnecessary
      panic reactions in the public, local governments in Tokatsu area collaborated
      with radiation specialists and conducted activities to provide local residents
      with accurate information on health effects from radiation. In addition to these
      activities, the authors offered one-to-one consultations with a radiologist for
      parents of small children and expecting mothers. They herein report this unique
      attempt, focusing on parents' anxiety and the age of their children. Taken
      together, this unique collaborative activity between local government and experts
      would be one of the procedures to relieve residents' anxiety. 

PMID- 25953793
TI  - Accumulation of accident-derived radiocesium in lake and coastal sediments at 300
      700 km distance from Fukushima area.
AB  - The accumulation of accident-derived radiocesium was investigated in nine water
      bodies located 300-700 km from the Fukushima Dai-ichi Nuclear Power Plant
      (FDNPP). (134)Cs from the accident was detected in surface sediment of five water
      bodies. The (134)Cs concentration, corrected to the time of the accident in 2011,
      was generally lower than that of (137)Cs, and its spatial pattern does not fully
      correspond to that of (137)Cs. These results suggest that radiocesium derived
      from both FDNPP and past global fallout can be separately observed and that the
      contributions of both sources are non-uniform within these sites. The (134)Cs
      inventory in surface sediments is smaller than its deposition, suggesting that
      almost all deposited (134)Cs remains within the catchment and/or a part has been
      discharged from the saline and brackish water bodies. 

PMID- 25953794
TI  - Changes in ambient dose equivalent rates around roads at Kawamata town after the
      Fukushima accident.
AB  - Changes in ambient dose equivalent rates noted through vehicle-borne surveys have
      elucidated ecological half-lives of radioactive caesium in the environment. To
      confirm that the ecological half-lives are appropriate for predicting ambient
      dose equivalent rates within living areas, it is important to ascertain ambient
      dose equivalent rates on/around roads. In this study, radiation monitoring
      on/around roads at Kawamata town, located about 37 km northwest of the Fukushima
      Daiichi Nuclear Power Plant, was performed using monitoring vehicles and survey
      meters. It was found that the ambient dose equivalent rates around roads were
      higher than those on roads as of October 2012. And withal the ecological half
      lives on roads were essentially consistent with those around roads. With dose
      predictions using ecological half-lives on roads, it is necessary to make
      corrections to ambient dose equivalent rates through the vehicle-borne surveys
      against those within living areas. 

PMID- 25953795
TI  - Influence of the Fukushima Dai-ichi Nuclear Power Plant accident on environmental
      radioactivity in Aomori Prefecture.
AB  - Radioactive nuclides with a short half-life, such as (131)I and (134)Cs, were
      detected in environmental samples collected in Aomori Prefecture after the Tokyo
      Electric Power Company Fukushima Dai-ichi Nuclear Power Plant accident in March
      2011. In addition, the observed (137)Cs concentration was increased over the
      background level. The gaseous (131)I concentration in air observed in April was
      higher than that observed in March immediately after the accident. Using a
      backward trajectory analysis, the authors found that the air mass had passed the
      vicinity of the Fukushima Dai-ichi Nuclear Power Plant when the gaseous (131)I
      concentration in air was increasing. Maximum (131)I and radioactive Cs
      concentrations in daily fallout samples collected in Aomori city were observed on
      28 April, when (131)I was also detected in air. (134)Cs and (137)Cs concentration
      ratios in pine needles and pasture grass were nearly equal to 1, which indicates
      that the source of these radionuclides was the nuclear power plant accident. 

PMID- 25953796
TI  - Hyper-radiosensitivity and induced radioresistance and bystander effects in
      rodent and human cells as a function of radiation quality.
AB  - In the past two decades, a body of experimental evidences in vitro has shown the
      presence of a plethora of phenomena occurring after low-dose irradiation
      [including hypersensitivity and induced radioresistance (IRR), adaptive response,
      bystander effect (BE) and genomic instability], which might imply a non-linear
      behaviour of cancer risk curves in the low-dose region and question the validity
      of the linear no-threshold model for cancer risk assessment in such a dose
      region. In this framework, a systematic investigation have been undertaken on non
      linear effects at low doses as a function of different radiation quality and
      cellular radiosensitivity and in terms of different biological end points. The
      present article reports the recent results on hyper-radiosensitivity and IRR and
      BE phenomena, in terms of clonogenic survival in V79 Chinese hamster cells and
      T98G human glioblastoma cells irradiated with protons and carbon ions with
      different energy, as a function of dose (and fluence). 

PMID- 25953797
TI  - Pregnancy, rheumatic heart disease, and cardiomyopathies: more on under
      recognized entities.

PMID- 25953798
TI  - Antenatal assessment of cardiac defects in the foetus.

PMID- 25953799
TI  - IonGAP: integrative bacterial genome analysis for Ion Torrent sequence data.
AB  - We introduce IonGAP, a publicly available Web platform designed for the analysis
      of whole bacterial genomes using Ion Torrent sequence data. Besides assembly, it
      integrates a variety of comparative genomics, annotation and bacterial
      classification routines, based on the widely used FASTQ, BAM and SRA file
      formats. Benchmarking with different datasets evidenced that IonGAP is a fast,
      powerful and simple-to-use bioinformatics tool. By releasing this platform, we
      aim to translate low-cost bacterial genome analysis for microbiological
      prevention and control in healthcare, agroalimentary and pharmaceutical industry
      applications. AVAILABILITY AND IMPLEMENTATION: IonGAP is hosted by the ITER's
      Teide-HPC supercomputer and is freely available on the Web for non-commercial use
      at http://iongap.hpc.iter.es. CONTACT: mcolesan@ull.edu.es or cflores@ull.edu.es
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 25953800
TI  - Identification of C2H2-ZF binding preferences from ChIP-seq data using RCADE.
AB  - Current methods for motif discovery from chromatin immunoprecipitation followed
      by sequencing (ChIP-seq) data often identify non-targeted transcription factor
      (TF) motifs, and are even further limited when peak sequences are similar due to
      common ancestry rather than common binding factors. The latter aspect
      particularly affects a large number of proteins from the Cys2His2 zinc finger
      (C2H2-ZF) class of TFs, as their binding sites are often dominated by endogenous
      retroelements that have highly similar sequences. Here, we present recognition
      code-assisted discovery of regulatory elements (RCADE) for motif discovery from
      C2H2-ZF ChIP-seq data. RCADE combines predictions from a DNA recognition code of
      C2H2-ZFs with ChIP-seq data to identify models that represent the genuine DNA
      binding preferences of C2H2-ZF proteins. We show that RCADE is able to identify
      generalizable binding models even from peaks that are exclusively located within
      the repeat regions of the genome, where state-of-the-art motif finding approaches
      largely fail. AVAILABILITY AND IMPLEMENTATION: RCADE is available as a webserver
      and also for download at http://rcade.ccbr.utoronto.ca/. SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online. CONTACT:
      t.hughes@utoronto.ca.

PMID- 25953801
TI  - BFC: correcting Illumina sequencing errors.
AB  - BFC is a free, fast and easy-to-use sequencing error corrector designed for
      Illumina short reads. It uses a non-greedy algorithm but still maintains a speed
      comparable to implementations based on greedy methods. In evaluations on real
      data, BFC appears to correct more errors with fewer overcorrections in comparison
      to existing tools. It particularly does well in suppressing systematic sequencing
      errors, which helps to improve the base accuracy of de novo assemblies.
      AVAILABILITY AND IMPLEMENTATION: https://github.com/lh3/bfc CONTACT:
      hengli@broadinstitute.org SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 25953802
TI  - Inhibition of factor IXa by the pegnivacogin system during cardiopulmonary
      bypass: a potential substitute for heparin. A study in baboons.
AB  - OBJECTIVES: Heparin and protamine are standard for anticoagulation and reversal
      for cardiopulmonary bypass (CPB). The REGADO biosciences protocol 1 (REG1)
      anticoagulant system, consisting of the Factor IXa (FIXa)-inhibitor pegnivacogin
      and its reversal agent (anivamersen), has been studied in patients undergoing
      coronary catheterization and in CPB in sheep and pigs. Prior to first human use
      in CPB, we wanted to test the safety and efficacy of REG1 in a primate model.
      METHODS: Fourteen baboons undergoing 2 h of CPB followed by 1 h of reperfusion
      were studied. Three received heparin/protamine and 11 received 1 of 2 doses of
      pegnivacogin followed by anivamersen. Thrombin-generating capacity was tested in
      additional in vitro experiments. RESULTS: Targeted drug levels and near-complete
      FIXa inhibition were achieved. Bypass was run uneventfully in all animals without
      any clotting in the circuit and bleeding was minimal in the two groups. However,
      in contrast to heparin-treated baboons, those receiving pegnivacogin/anivamersen
      displayed thrombi in the bypass cannulae upon cannulation and kidney cortical
      infarcts. Inter-species comparisons revealed that in the presence of high levels
      of FIXa inhibition, tissue factor-mediated thrombin generation in baboons was
      much higher than that in other species. CONCLUSIONS: These data highlight the
      limitations of the baboon model for assessing factor-specific coagulation
      inhibitors during CPB. The justification for Phase 1 human studies using REG1 for
      CPB is unclear.

PMID- 25953803
TI  - The indirect microscopic observation drug susceptibility assay demonstrated high
      concordance with the indirect MGIT method for pyrazinamide susceptibility
      testing.
AB  - OBJECTIVES: The microscopic observation drug susceptibility (MODS) assay has been
      used for Mycobacterium tuberculosis detection and anti-TB drug susceptibility
      tests for several years, and our study aimed to evaluate the accuracy of MODS in
      detecting pyrazinamide resistance in MDR TB suspects. METHODS: One hundred and
      forty-eight clinical isolates were collected from 148 MDR TB suspects in the
      Nanjing Chest Hospital, and the MODS and the mycobacteria growth indicator tube
      (MGIT) 960 methods for pyrazinamide susceptibility testing were conducted for
      each isolate independently. pncA gene sequencing was applied to confirm results
      showing discrepancy between the MODS and MGIT 960 methods. The McNemar chi(2)
      test was employed to evaluate the paired 2 * 2 table. RESULTS: Compared with the
      MGIT 960 method, the sensitivity and specificity of the MODS assay were 95.5% and
      93.3%, respectively, with a high accuracy of 94.5%. The kappa value of 0.89
      showed near-perfect agreement for the two methods in determining pyrazinamide
      susceptibility. Eight clinical isolates showed inconsistent results by MODS and
      MGIT 960. After sequencing the pncA gene of the eight isolates, MODS and MGIT 960
      showed no significant difference in detecting pyrazinamide resistance when
      compared with pncA gene sequencing (P = 0.655 for MODS and P = 0.564 for MGIT
      960). CONCLUSIONS: The high accuracy of MODS in detecting pyrazinamide resistance
      showed that the MODS method would be an alternative for pyrazinamide
      susceptibility testing; other mutations affecting resistance to pyrazinamide need
      to be identified in order to elucidate the discrepant results between phenotype-
      and genotype-based methods.

PMID- 25953804
TI  - The combination of ampicillin plus ceftaroline is synergistic against
      Enterococcus faecalis.

PMID- 25953805
TI  - Can therapeutic drug monitoring optimize exposure to piperacillin in febrile
      neutropenic patients with haematological malignancies? A randomized controlled
      trial.
AB  - OBJECTIVES: The objectives of this study were to describe piperacillin exposure
      in febrile neutropenia patients and determine whether therapeutic drug monitoring
      (TDM) can be used to increase the achievement of pharmacokinetic
      (PK)/pharmacodynamic (PD) targets. METHODS: In a prospective randomized
      controlled study (Australian New Zealand Registry, ACTRN12615000086561), patients
      were subjected to TDM for 3 consecutive days. Dose was adjusted in the
      intervention group to achieve a free drug concentration above the MIC for 100% of
      the dose interval (100% fT>MIC), which was also the primary outcome measure. The
      secondary PK/PD target was 50% fT>MIC. Duration of fever and days to recovery
      from neutropenia were recorded. RESULTS: Thirty-two patients were enrolled.
      Initially, patients received 4.5 g of piperacillin/tazobactam every 8 h or every
      6 h along with gentamicin co-therapy in 30/32 (94%) patients. At the first TDM,
      7/32 (22%) patients achieved 100% fT>MIC and 12/32 (38%) patients achieved 50%
      fT>MIC. Following dose adjustment, 11/16 (69%) of intervention patients versus
      3/16 (19%) of control patients (P = 0.012) attained 100% fT>MIC, and 15/16 (94%)
      of intervention patients versus 5/16 (31%) of control patients (P = 0.001)
      achieved 50% fT>MIC. After the third TDM, the proportion of patients attaining
      100% fT>MIC improved from a baseline 3/16 (19%) to 11/15 (73%) in the
      intervention group, while it declined from 4/16 (25%) to 1/15 (7%) in the control
      group. No difference was noted in the duration of fever and days to recovery from
      neutropenia. CONCLUSIONS: Conventional doses of piperacillin/tazobactam may not
      offer adequate piperacillin exposure in febrile neutropenic patients. TDM
      provides useful feedback of dosing adequacy to guide dose optimization.

PMID- 25953806
TI  - Comment on: Antimicrobial stewardship: the role of scientists?

PMID- 25953807
TI  - Time series analysis of the impact of an intervention in Tayside, Scotland to
      reduce primary care broad-spectrum antimicrobial use.
AB  - OBJECTIVES: Concern about Clostridium difficile infection (CDI) and resistance
      has driven interventions internationally to reduce broad-spectrum antimicrobial
      use. An intervention combining guidelines, education and feedback was implemented
      in Tayside, Scotland in 2009 aiming to reduce primary care prescribing of co
      amoxiclav, cephalosporins, fluoroquinolones and clindamycin ('4C
      antimicrobials'). Our aim was to assess the impact of this real-world
      intervention on antimicrobial prescribing rates. METHODS: We used interrupted
      time series with segmented regression analysis to examine associations between
      the intervention and changes in antimicrobial prescribing (quarterly rates of
      patients exposed to 4C antimicrobials, non-4C antimicrobials and any
      antimicrobial in 2005-12). RESULTS: The intervention was associated with a highly
      significant and sustained decrease in 4C antimicrobial prescribing, by 33.5% (95%
      CI -26.1 to -40.9), 42.2% (95% CI -34.2 to -50.2) and 55.5% (95% CI -45.9 to 
      65.1) at 6, 12 and 24 months after intervention, respectively. The effect was
      seen across all age groups, with the largest reductions in people aged 65 years
      and over (58.4% reduction at 24 months, 95% CI -46.7 to -70.1) and care home
      residents (65.6% reduction at 24 months, 95% CI -51.8 to -79.4). There were
      balancing increases in doxycycline, nitrofurantoin and trimethoprim prescribing
      as well as a reduction in macrolide prescribing. Total antimicrobial exposure did
      not change. CONCLUSIONS: A real-world intervention to reduce primary care
      prescribing of antimicrobials associated with CDI led to large, sustained
      reductions in the targeted prescribing, largely due to substitution with
      guideline-recommended antimicrobials rather than by avoiding antimicrobial use
      altogether. Further research is needed to examine the impact on antimicrobial
      resistance.

PMID- 25953809
TI  - Depressive Symptoms and Disability Risk Among Older White and Latino Adults by
      Nativity Status.
AB  - OBJECTIVE: To examine how the relationship between depressive symptoms and
      disability may vary by nativity status in later life. METHOD: This nationally
      representative prospective study of community-dwelling adults age 51 years and
      older in the Health and Retirement Study (1998-2010) used hierarchical linear
      modeling to examine how depressive symptoms (Center for Epidemiological Symptoms
      of Depression) and disability (instrumental activities of daily living [IADL];
      activities of daily living [ADL]) vary by nativity status (U.S.- vs. foreign
      born), accounting for changes in social support, health behaviors, and health
      conditions. RESULTS: Depressive symptoms were associated with increased IADL and
      ADL disability among Latinos compared with Whites; foreign-born Latinos had lower
      than expected depressive symptom-related IADL and ADL (0.82; p <= .001)
      disability. DISCUSSION: Given that U.S.-born Latinos had similar or poorer
      depressive symptom-related disability outcomes than Whites, interventions focused
      on early detection and treatment of depressive symptoms for this group are
      warranted and may improve disablement outcomes.

PMID- 25953808
TI  - Parallel evolutionary pathways to antibiotic resistance selected by biocide
      exposure.
AB  - OBJECTIVES: Biocides are widely used to prevent infection. We aimed to determine
      whether exposure of Salmonella to various biocides could act as a driver of
      antibiotic resistance. METHODS: Salmonella enterica serovar Typhimurium was
      exposed to four biocides with differing modes of action. Antibiotic-resistant
      mutants were selected during exposure to all biocides and characterized
      phenotypically and genotypically to identify mechanisms of resistance. RESULTS:
      All biocides tested selected MDR mutants with decreased antibiotic
      susceptibility; these occurred randomly throughout the experiments. Mutations
      that resulted in de-repression of the multidrug efflux pump AcrAB-TolC were seen
      in MDR mutants. A novel mutation in rpoA was also selected and contributed to the
      MDR phenotype. Other mutants were highly resistant to both quinolone antibiotics
      and the biocide triclosan. CONCLUSIONS: This study shows that exposure of
      bacteria to biocides can select for antibiotic-resistant mutants and this is
      mediated by clinically relevant mechanisms of resistance prevalent in human
      pathogens.

PMID- 25953810
TI  - Economic Status and Old-Age Health in Poverty-Stricken Myanmar.
AB  - OBJECTIVE: We examine the association between poverty, economic inequality, and
      health among elderly in Myanmar. METHOD: We analyze 2012 data from Myanmar's
      first representative survey of older adults to investigate how health indicators
      vary across wealth quintiles as measured by household possessions and housing
      quality. RESULTS: Poverty and poor health are pervasive. Self-assessed health,
      sensory impairment, and functional limitation consistently improve with higher
      wealth levels regardless of socio-demographic controls. Differentials in self
      rated health and sensory impairment between the bottom and second quintiles are
      clearly evident, suggesting that relative economic inequality matters even among
      very poor elders and that a small difference in wealth can matter in an extreme
      poverty setting. DISCUSSION: Findings support a global theory of economic
      gradients in health regardless of level of societal poverty. Modest efforts to
      improve the standard of living among elderly may improve not only their material
      well-being but also their health.

PMID- 25953811
TI  - Does Neighborhood Disorder Predict Recovery From Mobility Limitation? Findings
      From the Health and Retirement Study.
AB  - OBJECTIVE: This research explores whether perceptions of physical neighborhood
      disorder predict recovery from mobility limitation over a 2-year period and
      examines whether psychosocial factors (i.e., depressive symptomology and mastery)
      and physical activity are salient mediators. METHOD: Using data from the Health
      and Retirement Study (HRS): Participant Lifestyle Questionnaire (2008-2010), odds
      ratio estimates of recovery were ascertained using binary logistic regression,
      and post hoc Sobel tests were conducted to formally assess mediation. RESULTS:
      Net of demographic characteristics and socioeconomic status, increased
      neighborhood disorder was associated with lower odds of recovery. However, both
      psychosocial indicators and physical activity were significant individual partial
      mediators, which suggest neighborhood disorder influences recovery from physical
      impairment via psychosocial processes and barriers to physical activity.
      DISCUSSION: Reducing neighborhood disorder may enhance older residents'
      psychosocial well-being and improve participation in physical activity, thus
      increasing recovery from mobility limitation and preventing subsequent
      disability.

PMID- 25953812
TI  - Risk Factors for Social Isolation in Older Korean Americans.
AB  - OBJECTIVE: Given the importance of social ties and connectedness in the lives of
      older ethnic immigrants, the present study examined the prevalence of social
      isolation and its risk factors in older Korean Americans. METHOD: Using survey
      data from 1,301 participants (Mage = 70.5, SD = 7.24), risk groups for marginal
      social ties with family and friends were identified and predictors of each type
      of social isolation explored. RESULTS: Male gender and poorer rating of health
      were identified as common risk factors for marginal ties to both family and
      friends. Findings also present specific risk factors for each type of social
      isolation. For example, an increased risk of having marginal ties with friends
      was observed among individuals with perceived financial strain, greater
      functional impairment, and a shorter stay in the United States. DISCUSSION: The
      common and specific risk factors should be incorporated in programs to reduce
      social isolation in older immigrant populations.

PMID- 25953813
TI  - Long-Term BMI Trajectories and Health in Older Adults: Hierarchical Clustering of
      Functional Curves.
AB  - OBJECTIVE: This project contributes to the emerging research that aims to
      identify distinct body mass index (BMI) trajectory types in the population. We
      identify clusters of long-term BMI curves among older adults and determine how
      the clusters differ with respect to initial health. METHOD: Health and Retirement
      Study cohort (N = 9,893) with BMI information collected in up to 10 waves (1992
      2010) is analyzed using a powerful cutting-edge approach: hierarchical clustering
      of BMI functions estimated via the Principal Analysis by Conditional Expectations
      (PACE) algorithm. RESULTS: Three BMI trajectory clusters emerged for each gender:
      stable, gaining, and losing. The initial health of the gaining and stable groups
      in both genders was comparable; the losing cluster experienced significantly
      poorer health at baseline. DISCUSSION: BMI trajectories among older adults
      cluster into distinct types in both genders, and the clusters vary substantially
      in initial health. Weight loss but not gain is associated with poor initial
      health in this age group.

PMID- 25953814
TI  - Trajectories of Aging Long-Term Mexican American Heroin Injectors: The "Maturing
      Out" Paradox.
AB  - OBJECTIVE: To examine the applicability of the "maturing out" theory to a sample
      of aging Mexican American men who are long-term heroin injectors. METHOD:
      Ethnographic data were collected as part of a cross-sectional study of aging
      Mexican American heroin users in Houston with 20 current heroin users. RESULTS:
      Findings indicate that dysfunctions that emerge in the heroin lifestyle lead not
      to cessation but rather to "maturing in," a specific process of social
      readjustment that returns the heroin user to a stable maintenance pattern of use
      instead of a recovery phase. This process of paradoxical maturing out can be
      attributed to the unconditional social support provided to the heroin user by
      family, peers, and the tecato subculture embedded in Mexican American
      communities. DISCUSSION: Results highlight the implications for the intersection
      of heroin-related conditions, natural age-related impairments, and cognitive
      functioning that make this population increasingly susceptible to adverse health
      consequences.

PMID- 25953815
TI  - Depressed Mood in Middle-Aged and Older Adults in Europe and the United States: A
      Comparative Study Using Anchoring Vignettes.
AB  - OBJECTIVE: To compare self-ratings of depressed mood in middle-aged and older
      adults in the United States and nine European countries after adjustment by
      anchoring vignettes. METHOD: Samples were drawn from three large surveys of
      middle-aged and older adults: the U.S. Health and Retirement Study, the English
      Longitudinal Study of Aging (ELSA), and the Survey of Health, Ageing and
      Retirement in Europe. Self-ratings of depressed mood were compared across
      countries before and after adjustment by anchoring vignettes depicting cases with
      different levels of depressed mood. RESULTS: Compared with Europeans as a group,
      Americans rated both the cases presented in the vignettes and themselves as more
      depressed. However, after adjustment by vignette ratings, Americans appeared to
      be less depressed than their counterparts in all but two European countries.
      DISCUSSION: Cultural differences in mental health norms reflected in vignette
      rating may partly explain between-country differences in self-reported depressive
      symptoms and perhaps other psychiatric complaints.

PMID- 25953816
TI  - Racial/Ethnic and Socioeconomic Disparities in Hearing Health Care Among Older
      Americans.
AB  - OBJECTIVE: Hearing impairment is highly prevalent, but little is known about
      hearing health care among older minority adults. METHOD: We analyzed nationally
      representative, cross-sectional data from 1,544 older adults >= 70 years with
      audiometry and hearing care data from the 2005-2006 and 2009-2010 National Health
      and Nutritional Examination Surveys. RESULTS: After adjusting for age and speech
      frequency pure tone average, Blacks (odds ratio [OR] = 1.68, vs. Whites) and
      those with greater education (OR = 1.63, >= college vs. < high school) were more
      likely to report recent hearing testing, while White older adults and those with
      greater socioeconomic status were more likely to report regular hearing aid use
      (all ps < .05). Based on a multivariate analysis, Blacks were not more likely
      than Whites to use hearing aids despite being more likely to have had recent
      hearing testing. DISCUSSION: Racial/ethnic and socioeconomic disparities exist in
      hearing health care and represent critical areas for research and intervention.

PMID- 25953817
TI  - 2.2 A resolution cryo-EM structure of beta-galactosidase in complex with a cell
      permeant inhibitor.
AB  - Cryo-electron microscopy (cryo-EM) is rapidly emerging as a powerful tool for
      protein structure determination at high resolution. Here we report the structure
      of a complex between Escherichia coli beta-galactosidase and the cell-permeant
      inhibitor phenylethyl beta-D-thiogalactopyranoside (PETG), determined by cryo-EM
      at an average resolution of ~2.2 angstroms (A). Besides the PETG ligand, we
      identified densities in the map for ~800 water molecules and for magnesium and
      sodium ions. Although it is likely that continued advances in detector technology
      may further enhance resolution, our findings demonstrate that preparation of
      specimens of adequate quality and intrinsic protein flexibility, rather than
      imaging or image-processing technologies, now represent the major bottlenecks to
      routinely achieving resolutions close to 2 A using single-particle cryo-EM.

PMID- 25953818
TI  - Multiplex single cell profiling of chromatin accessibility by combinatorial
      cellular indexing.
AB  - Technical advances have enabled the collection of genome and transcriptome data
      sets with single-cell resolution. However, single-cell characterization of the
      epigenome has remained challenging. Furthermore, because cells must be physically
      separated before biochemical processing, conventional single-cell preparatory
      methods scale linearly. We applied combinatorial cellular indexing to measure
      chromatin accessibility in thousands of single cells per assay, circumventing the
      need for compartmentalization of individual cells. We report chromatin
      accessibility profiles from more than 15,000 single cells and use these data to
      cluster cells on the basis of chromatin accessibility landscapes. We identify
      modules of coordinately regulated chromatin accessibility at the level of single
      cells both between and within cell types, with a scalable method that may
      accelerate progress toward a human cell atlas. 

PMID- 25953819
TI  - Social sciences. The rise of the social algorithm.

PMID- 25953820
TI  - Political science. Exposure to ideologically diverse news and opinion on
      Facebook.
AB  - Exposure to news, opinion, and civic information increasingly occurs through
      social media. How do these online networks influence exposure to perspectives
      that cut across ideological lines? Using deidentified data, we examined how 10.1
      million U.S. Facebook users interact with socially shared news. We directly
      measured ideological homophily in friend networks and examined the extent to
      which heterogeneous friends could potentially expose individuals to cross-cutting
      content. We then quantified the extent to which individuals encounter
      comparatively more or less diverse content while interacting via Facebook's
      algorithmically ranked News Feed and further studied users' choices to click
      through to ideologically discordant content. Compared with algorithmic ranking,
      individuals' choices played a stronger role in limiting exposure to cross-cutting
      content. 

PMID- 25953821
TI  - Embryo development. A cysteine-clamp gene drives embryo polarity in the midge
      Chironomus.
AB  - In the fruit fly Drosophila, head formation is driven by a single gene, bicoid,
      which generates head-to-tail polarity of the main embryonic axis. Bicoid
      deficiency results in embryos with tail-to-tail polarity and no head. However,
      most insects lack bicoid, and the molecular mechanism for establishing head-to
      tail polarity is poorly understood. We have identified a gene that establishes
      head-to-tail polarity of the mosquito-like midge, Chironomus riparius. This gene,
      named panish, encodes a cysteine-clamp DNA binding domain and operates through a
      different mechanism than bicoid. This finding, combined with the observation that
      the phylogenetic distributions of panish and bicoid are limited to specific
      families of flies, reveals frequent evolutionary changes of body axis
      determinants and a remarkable opportunity to study gene regulatory network
      evolution. 

PMID- 25953822
TI  - Planetary science. Low-altitude magnetic field measurements by MESSENGER reveal
      Mercury's ancient crustal field.
AB  - Magnetized rocks can record the history of the magnetic field of a planet, a key
      constraint for understanding its evolution. From orbital vector magnetic field
      measurements of Mercury taken by the MErcury Surface, Space ENvironment,
      GEochemistry, and Ranging (MESSENGER) spacecraft at altitudes below 150
      kilometers, we have detected remanent magnetization in Mercury's crust. We infer
      a lower bound on the average age of magnetization of 3.7 to 3.9 billion years.
      Our findings indicate that a global magnetic field driven by dynamo processes in
      the fluid outer core operated early in Mercury's history. Ancient field strengths
      that range from those similar to Mercury's present dipole field to Earth-like
      values are consistent with the magnetic field observations and with the low iron
      content of Mercury's crust inferred from MESSENGER elemental composition data. 

PMID- 25953824
TI  - Intracoronary injection of large stem cells: size matters.

PMID- 25953823
TI  - Intracoronary delivery of self-assembling heart-derived microtissues
      (cardiospheres) for prevention of adverse remodeling in a pig model of
      convalescent myocardial infarction.
AB  - BACKGROUND: Preclinical studies in rodents and pigs indicate that the self
      assembling microtissues known as cardiospheres may be more effective than
      dispersed cardiosphere-derived cells. However, the more desirable intracoronary
      route has been assumed to be unsafe for cardiosphere delivery: Cardiospheres are
      large (30-150 MUm), raising concerns about likely microembolization. We
      questioned these negative assumptions by evaluating the safety and efficacy of
      optimized intracoronary delivery of cardiospheres in a porcine model of
      convalescent myocardial infarction. METHODS AND RESULTS: First, we standardized
      the size of cardiospheres by modifying culture conditions. Then, dosage was
      determined by infusing escalating doses of cardiospheres in the left anterior
      descending artery of naive pigs, looking for acute adverse effects. Finally, in a
      randomized efficacy study, 14 minipigs received allogeneic cardiospheres (1.3 *
      10(6)) or vehicle 1 month after myocardial infarction. Animals underwent magnetic
      resonance imaging before infusion and 1 month later to assess left ventricular
      ejection fraction, scar mass, and viable mass. In the dosing study, we did not
      observe any evidence of microembolization after cardiosphere infusion. In the
      post-myocardial infarction study, cardiospheres preserved LV function, reduced
      scar mass and increased viable mass, whereas placebo did not. Moreover,
      cardiosphere decreased collagen content, and increased vessel densities and
      myocardial perfusion. Importantly, intracoronary cardiospheres decreased left
      ventricular end-diastolic pressure and increased cardiac output. CONCLUSIONS:
      Intracoronary delivery of cardiospheres is safe. Intracoronary cardiospheres are
      also remarkably effective in decreasing scar, halting adverse remodeling,
      increasing myocardial perfusion, and improving hemodynamic status after
      myocardial infarction in pigs. Thus, cardiospheres may be viable therapeutic
      candidates for intracoronary infusion in selected myocardial disorders.

PMID- 25953825
TI  - Neurology of Nutritional Vitamin B12 Deficiency in Infants: Case Series From
      India and Literature Review.
AB  - We studied 27 infants aged 6 to 27 months with vitamin B12 deficiency also known
      as "infantile tremor syndrome" in India. All were exclusively breast-fed by
      vegetarian mothers. Developmental delay or regression, pallor, skin
      hyperpigmentation, and sparse brown hair were present in all. Majority were
      hypotonic and involuntary movements were encountered in 18. Anemia and
      macrocytosis was found in 83% and 71% infants, respectively. Low serum vitamin
      B12 was present in 12 of 21 infants. Seven of the 9 infants with normal serum
      vitamin B12 had received vitamin B12 before referral. Twelve mothers had low
      serum vitamin B12. Cerebral atrophy was present in all the 9 infants who
      underwent neuroimaging. Treatment with vitamin B12 resulted in dramatic
      improvement in general activity and appetite within 48 to 72 hours followed by
      return of lost milestones. Tremors resolved in all by 3 to 4 weeks. Nutritional
      vitamin B12 deficiency is a treatable cause of neurologic dysfunction in infants.

PMID- 25953826
TI  - Cardiac Autonomic Dysfunction in Patients With Infantile Spasm and the Effect of
      Adrenocorticotropic Hormone Treatment.
AB  - Infantile spasm is an age-dependent epileptic-encephalopathy syndrome. Cardiac
      autonomic function is frequently altered in epilepsy. In this study, we examined
      heart rate variability in patients with infantile spasm before and after
      treatment. Nineteen patients with infantile spasm and 13 healthy comparisons were
      enrolled in the study. Cardiac rhythm was recorded with a Holter device for 24
      hours before adrenocorticotropic hormone (ACTH) (Synacthen depot) and B6 vitamin
      administration and 1 month after treatment. Heart rate variability analysis found
      lower heart rate variability parameters in patients with infantile spasm at the
      onset of the syndrome, prior to treatment with ACTH. The time domain parameters
      of heart rate variability values showed a statistically significant increase
      following ACTH treatment. Our data suggest that patients with infantile spasm
      exhibit lower heart rate variability parameters, and the treatment of spasms with
      ACTH and B6 together diminished the autonomic dysfunction in our cohort. 

PMID- 25953827
TI  - Integration of transcriptome and methylome analysis of aldosterone-producing
      adenomas.
AB  - OBJECTIVE: The pathophysiology of aldosterone-producing adenomas (APA) has been
      investigated intensively through genetic and genomic approaches. However, the
      role of epigenetics in APA is not fully understood. In the present study, we
      explored the relationship between gene expression and DNA methylation status in
      APA. METHODS: We conducted an integrated analysis of transcriptome and methylome
      data of paired APA-adjacent adrenal gland (AAG) samples from the same patient.
      The adrenal specimens were obtained from seven Japanese patients with APA who
      underwent adrenalectomy. Gene expression and genome-wide CpG methylation profiles
      were obtained from RNA and DNA samples that were extracted from those seven
      paired tissues. RESULTS: Methylome analysis showed global CpG hypomethylation in
      APA relative to AAG. The integration of gene expression and methylation status
      showed that 34 genes were up-regulated with CpG hypomethylation in APA. Of these,
      three genes (CYP11B2, MC2R, and HPX) may be related to aldosterone production,
      and five genes (PRRX1, RAB38, FAP, GCNT2, and ASB4) are potentially involved in
      tumorigenesis. CONCLUSION: The present study is the first methylome analysis to
      compare APA with AAG in the same patients. Our integrated analysis of
      transcriptome and methylome revealed DNA hypomethylation in APA and identified
      several up-regulated genes with DNA hypomethylation that may be involved in
      aldosterone production and tumorigenesis.

PMID- 25953828
TI  - ACTH after 15 min distinguishes between Cushing's disease and ectopic Cushing's
      syndrome: a proposal for a short and simple CRH test.
AB  - OBJECTIVE: The aim of the present study was to validate criteria of corticotropin
      releasing hormone (CRH) stimulation and 8 mg dexamethasone suppression (high-dose
      dexamethasone suppression, HDDS) to distinguish the etiology of ACTH-dependent
      Cushing's syndrome. SUBJECTS AND METHODS: We retrospectively analyzed cortisol
      and ACTH after the injection of 100 MUg human CRH in confirmed Cushing's disease
      (CD, n=78) and confirmed ectopic Cushing's syndrome (ECS, n=18). Cortisol and
      ACTH increase (in percentage above basal (%B)) at each time point, maximal
      increase (Deltamax %B), and area under the curve (AUC %B) were analyzed using
      receiver operator characteristics (ROC) curve analyses. Cortisol suppression (%B)
      after 8 mg of dexamethasone was evaluated as a supplementary criterion. RESULTS:
      An increase in ACTH of >= 43%B at 15 min after CRH was the strongest predictor of
      CD, with a positive likelihood ratio of 14.0, a sensitivity of 83%, a specificity
      of 94%, a positive predictive value of 98% and a negative predictive value of
      58%. All of the other criteria of stimulated ACTH and cortisol levels were not
      superior in predicting CD in response to CRH injection. The addition of cortisol
      suppression by dexamethasone did not increase the discriminatory power. However,
      the combination of a positive ACTH response at 15 min and a positive HDDS test
      excluded ECS in all cases. CONCLUSION: The present findings support the use of
      plasma ACTH levels 15 min after the injection of human CRH as a response
      criterion for distinguishing between CD and ECS. The addition of the HDDS test is
      helpful for excluding ECS when both tests are positive.

PMID- 25953829
TI  - Postprandial incretin and islet hormone responses and dipeptidyl-peptidase 4
      enzymatic activity in patients with maturity onset diabetes of the young.
AB  - OBJECTIVE: The role of the incretin hormones in the pathophysiology of maturity
      onset diabetes of the young (MODY) is unclear. DESIGN: We studied the
      postprandial plasma responses of glucagon, incretin hormones (glucagon-like
      peptide 1 (GLP1) and glucose-dependent insulinotropic polypeptide (GIP)) and
      dipeptidyl-peptidase 4 (DPP4) enzymatic activity in patients with glucokinase
      (GCK) diabetes (MODY2) and hepatocyte nuclear factor 1alpha (HNF1A) diabetes
      (MODY3) as well as in matched healthy individuals (CTRLs). SUBJECTS AND METHODS:
      Ten patients with MODY2 (mean age +/- S.E.M. 43 +/- 5 years; BMI 24 +/- 2
      kg/m(2); fasting plasma glucose (FPG) 7.1 +/- 0.3 mmol/l: HbA1c 6.6 +/- 0.2%),
      ten patients with MODY3 (age 31 +/- 3 years; BMI 24 +/- 1 kg/m(2); FPG 8.9 +/-
      0.8 mmol/l; HbA1c 7.0 +/- 0.3%) and ten CTRLs (age 40 +/- 5 years; BMI 24 +/- 1
      kg/m(2); FPG 5.1 +/- 0.1 mmol/l; HbA1c 5.3 +/- 0.1%) were examined with a liquid
      test meal. RESULTS: All of the groups exhibited similar baseline values of
      glucagon (MODY2: 7 +/- 1 pmol/l; MODY3: 6 +/- 1 pmol/l; CTRLs: 8 +/- 2 pmol/l,
      P=0.787), but patients with MODY3 exhibited postprandial hyperglucagonaemia (area
      under the curve (AUC) 838 +/- 108 min * pmol/l) as compared to CTRLs (182 +/- 176
      min * pmol/l, P=0.005) and tended to have a greater response than did patients
      with MODY2 (410 +/- 154 min * pmol/l, P=0.063). Similar peak concentrations and
      AUCs for plasma GIP and plasma GLP1 were observed across the groups. Increased
      fasting DPP4 activity was seen in patients with MODY3 (17.7 +/- 1.2 mU/ml) vs
      CTRLs (13.6 +/- 0.8 mU/ml, P=0.011), but the amount of activity was similar to
      that in patients with MODY2 (15.0 +/- 0.7 mU/ml, P=0.133). CONCLUSION: The
      pathophysiology of MODY3 includes exaggerated postprandial glucagon responses and
      increased fasting DPP4 enzymatic activity but normal postprandial incretin
      responses both in patients with MODY2 and in patients with MODY3.

PMID- 25953830
TI  - Neutrophil:lymphocyte ratio is positively related to type 2 diabetes in a large
      scale adult population: a Tianjin Chronic Low-Grade Systemic Inflammation and
      Health cohort study.
AB  - AIM: It is widely known that inflammation is related to type 2 diabetes (T2D),
      but few studies have shown a direct relationship between the immune system and
      T2D using a reliable biomarker. Neutrophil:lymphocyte ratio (NLR) is an easy-to
      analyze inflammation biomarker, but few studies have assessed the relationship
      between NLR and T2D. In order to evaluate how NLR is related to T2D, we designed
      a large-scale cross-sectional and prospective cohort study in an adult
      population. SUBJECTS AND METHODS: Participants were recruited from the Tianjin
      Medical University General Hospital-Health Management Centre. Both a baseline
      cross-sectional (n=87,686) and a prospective (n=38,074) assessment were
      performed. Participants without a history of T2D were followed up for ~ 6 years
      (with a median follow-up of 2.7 years). Adjusted logistic and Cox proportional
      hazards regression models were used to assess relationships between the quintiles
      of NLR and T2D (covariates: age, sex, BMI, smoking status, drinking status,
      hypertension, hyperlipidemia, and family history of cardiovascular disease,
      hypertension, hyperlipidemia, or diabetes). RESULTS: The prevalence and incidence
      of T2D were 4.9% and 6.8/1000 person-years respectively. The adjusted odds ratio
      and hazard ratio (95% CI) of the highest NLR quintile were 1.34 (1.21, 1.49) and
      1.39 (1.09, 1.78) (both P for trend <0.01) respectively as compared to the lowest
      quintile of NLR. Leukocyte, neutrophil, and lymphocyte counts do not
      significantly predict the eventual development of T2D. CONCLUSION: The present
      study demonstrates that NLR is related to the prevalence and incidence of T2D,
      and it suggests that NLR may be an efficient and accurate prognostic biomarker
      for T2D.

PMID- 25953831
TI  - A NAD-dependent glutamate dehydrogenase coordinates metabolism with cell division
      in Caulobacter crescentus.
AB  - Coupling cell cycle with nutrient availability is a crucial process for all
      living cells. But how bacteria control cell division according to metabolic
      supplies remains poorly understood. Here, we describe a molecular mechanism that
      coordinates central metabolism with cell division in the alpha-proteobacterium
      Caulobacter crescentus. This mechanism involves the NAD-dependent glutamate
      dehydrogenase GdhZ and the oxidoreductase-like KidO. While enzymatically active
      GdhZ directly interferes with FtsZ polymerization by stimulating its GTPase
      activity, KidO bound to NADH destabilizes lateral interactions between FtsZ
      protofilaments. Both GdhZ and KidO share the same regulatory network to
      concomitantly stimulate the rapid disassembly of the Z-ring, necessary for the
      subsequent release of progeny cells. Thus, this mechanism illustrates how
      proteins initially dedicated to metabolism coordinate cell cycle progression with
      nutrient availability. 

PMID- 25953832
TI  - Intranasal scopolamine affects the semicircular canals centrally and
      peripherally.
AB  - Space motion sickness (SMS), a condition caused by an intravestibular conflict,
      remains an important obstacle that astronauts encounter during the first days in
      space. Promethazine is currently the standard treatment of SMS, but scopolamine
      is used by some astronauts to prevent SMS. However, the oral and transdermal
      routes of administration of scopolamine are known to have substantial drawbacks.
      Intranasal administration of scopolamine ensures a fast absorption and rapid
      onset of therapeutic effect, which might prove to be suitable for use during
      spaceflights. The aim of this study was to evaluate the effects of intranasally
      administered scopolamine (0.4 mg) on the semicircular canals (SCCs) and the
      otoliths. This double-blind, placebo-controlled study was performed on 19 healthy
      male subjects. The function of the horizontal SCC and the vestibulo-ocular
      reflex, as well as the saccular function and utricular function, were evaluated.
      Scopolamine turned out to affect mainly the SCCs centrally and peripherally but
      also the utricles to a lesser extent. Centrally, the most probable site of action
      is the medial vestibular nucleus, where the highest density of muscarinic
      receptors has been demonstrated and afferent fibers from the SCCs and utricles
      synapse. Furthermore, our results suggest the presence of muscarinic receptors in
      the peripheral vestibular system on which scopolamine has a suppressive effect.
      Given the depressant actions on the SCCs, it is suggested that the
      pharmacodynamic effect of scopolamine may be attributed to the obliteration of
      intravestibular conflict that arises during (S)MS. 

PMID- 25953833
TI  - Neural regulation of hypoxia-inducible factors and redox state drives the
      pathogenesis of hypertension in a rodent model of sleep apnea.
AB  - Obstructive sleep apnea (OSA) is one of the most common causes of hypertension in
      western societies. OSA causes chronic intermittent hypoxia (CIH) in specialized
      O2-sensing glomus cells of the carotid body. CIH generates increased reactive
      oxygen species (ROS) that trigger a feedforward mechanism in which increased
      intracellular calcium levels ([Ca(2+)]i) trigger increased HIF-1alpha synthesis
      and increased HIF-2alpha degradation. As a result, the normal homeostatic balance
      between HIF-1alpha-dependent prooxidant and HIF-2alpha-dependent antioxidant
      enzymes is disrupted, leading to further increases in ROS. Carotid body sensory
      nerves project to the nucleus tractus solitarii, from which the information is
      relayed via interneurons to the rostral ventrolateral medulla in the brain stem,
      which sends sympathetic neurons to the adrenal medulla to stimulate the release
      of epinephrine and norepinephrine, catecholamines that increase blood pressure.
      At each synapse, neurotransmitters trigger increased [Ca(2+)]i, HIF-1alpha:HIF
      2alpha, and Nox2:Sod2 activity that generates increased ROS levels. These
      responses are not observed in other regions of the brain stem that do not receive
      input from the carotid body or signal to the sympathetic nervous system. Thus
      sympathetic nervous system homeostasis is dependent on a balance between HIF
      1alpha and HIF-2alpha, disruption of which results in hypertension in OSA
      patients.

PMID- 25953835
TI  - Heat shock protein 70 overexpression does not attenuate atrophy in botulinum
      neurotoxin type A-treated skeletal muscle.
AB  - Botulinum neurotoxin type A (BoNT/A) is used clinically to induce therapeutic
      chemical denervation of spastically contracted skeletal muscles. However, BoNT/A
      administration can also cause atrophy. We sought to determine whether a major
      proteolytic pathway contributing to atrophy in multiple models of muscle wasting,
      the ubiquitin proteasome system (UPS), is involved in BoNT/A-induced atrophy.
      Three and ten days following BoNT/A injection of rat hindlimb, soleus muscle
      fiber cross-sectional area was reduced 25 and 65%, respectively. The
      transcriptional activity of NF-kappaB and Foxo was significantly elevated at 3
      days (2- to 4-fold) and 10 days (5- to 6-fold). Muscle RING-finger protein-1
      (MuRF1) activity was elevated (2-fold) after 3 days but not 10 days, while
      atrogin-1 activity was not elevated at any time point. BoNT/A-induced
      polyubiquitination occurred after 3 days (3-fold increase) but was totally absent
      after 10 days. Proteasome activity was elevated (1.5- to 2-fold) after 3 and 10
      days. We employed the use of heat shock protein 70 (Hsp70) to inhibit NF-kappaB
      and Foxo transcriptional activity. Electrotransfer of Hsp70 into rat soleus,
      before BoNT/A administration, was insufficient to attenuate atrophy. It was also
      insufficient to decrease BoNT/A-induced Foxo activity at 3 days, although NF
      kappaB activity was abolished. By 10 days both NF-kappaB and Foxo activation were
      abolished by Hsp70. Hsp70-overexpression was unable to alter the levels of BoNT/A
      induced effects on MuRF1/atrogin-1, polyubiquitination, or proteasome activity.
      In conclusion, Hsp70 overexpression is insufficient to attenuate BoNT/A-induced
      atrophy. It remains unclear what proteolytic mechanism/s are contributing to
      BoNT/A-induced atrophy, although a Foxo-MuRF1-ubiquitin-proteasome contribution
      may exist, at least in early BoNT/A-induced atrophy. Further clarification of UPS
      involvement in BoNT/A-induced atrophy is warranted. 

PMID- 25953834
TI  - A critical review of mechanisms regulating remote preconditioning-induced brain
      protection.
AB  - Remote preconditioning (rPC) is the phenomenon whereby brief organ ischemia
      evokes an endogenous response such that a different (remote) organ is protected
      against subsequent, normally injurious ischemia. Experiments show rPC to be
      effective at evoking cardioprotection against ischemic heart injury and, more
      recently, neuroprotection against brain ischemia. Such is the enthusiasm for rPC
      that human studies have been initiated. Clinical trials suggest rPC to be safe
      (phase II trial) and effective in reducing stroke incidence in a population with
      high stroke risk. However, despite the therapeutic potential of rPC, there is a
      large gap in knowledge regarding the effector mechanisms of rPC and how it might
      be orchestrated to improve outcome after stroke. Here we provide a critical
      review of mechanisms that are directly attributable to rPC-induced
      neuroprotection in preclinical trials of rPC.

PMID- 25953837
TI  - Mortality, admission rates and outpatient use among frequent users of emergency
      departments: a systematic review.
AB  - OBJECTIVE: This systematic review examines whether frequent emergency department
      (ED) users experience higher mortality, hospital admissions and outpatient visits
      than non-frequent ED users. DESIGN: We published an a priori study protocol in
      PROSPERO. Our search strategy combined terms for 'frequent users' and 'emergency
      department'. At least two independent reviewers screened, selected, assessed
      quality and extracted data. Third-party adjudication resolved conflicts. Results
      were synthesised based on median effect sizes. DATA SOURCES: We searched seven
      electronic databases with no limits and performed an extensive grey literature
      search. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included observational
      analytical studies that focused on adult patients, had a comparison group of non
      frequent ED users and reported deaths, admissions and/or outpatient outcomes.
      RESULTS: The search strategy identified 4004 citations; 374 were screened by full
      text and 31 cohort and cross-sectional studies were included. Authors used many
      different definitions to describe frequent users; the overall quality of the
      included studies was moderate. Across seven studies examining mortality, frequent
      users had a median 2.2-fold increased odds of mortality compared with non
      frequent users. Twenty-eight studies assessing hospital admissions found a median
      increased odds of admissions per visit at 1.16 and of admissions per patient at
      2.58. Ten studies reported outpatient visits with a median 2.65-fold increased
      risk of having at least one outpatient encounter post-ED visit. CONCLUSIONS:
      Frequent ED users appear to experience higher mortality, hospital admissions and
      outpatient visits compared with non-frequent users, and may benefit from targeted
      interventions. Standardised definitions to facilitate comparable research are
      urgently needed. REVIEW REGISTRATION NUMBER: PROSPERO (CRD42013005855).

PMID- 25953836
TI  - Can breathing-like pressure oscillations reverse or prevent narrowing of small
      intact airways?
AB  - Periodic length fluctuations of airway smooth muscle during breathing are thought
      to modulate airway responsiveness in vivo. Recent animal and human intact airway
      studies have shown that pressure fluctuations simulating breathing can only
      marginally reverse airway narrowing and are ineffective at protecting against
      future narrowing. However, these previous studies were performed on relatively
      large (>5 mm diameter) airways, which are inherently stiffer than smaller airways
      for which a preponderance of airway constriction in asthma likely occurs. The
      goal of this study was to determine the effectiveness of breathing-like
      transmural pressure oscillations to reverse induced narrowing and/or protect
      against future narrowing of smaller, more compliant intact airways. We
      constricted smaller (luminal diameter = 2.92 +/- 0.29 mm) intact airway segments
      twice with ACh (10(-6) M), once while applying tidal-like pressure oscillations
      (5-15 cmH2O) before, during, and after inducing constriction (Pre + Post) and
      again while only imposing the tidal-like pressure oscillation after induced
      constriction (Post Only). Smaller airways were 128% more compliant than
      previously studied larger airways. This increased compliance translated into 196%
      more strain and 76% greater recovery (41 vs. 23%) because of tidal-like pressure
      oscillations. Larger pressure oscillations (5-25 cmH2O) caused more recovery
      (77.5 +/- 16.5%). However, pressure oscillations applied before and during
      constriction resulted in the same steady-state diameter as when pressure
      oscillations were only applied after constriction. These data show that reduced
      straining of the airways before a challenge likely does not contribute to the
      emergence of airway hyperreactivity observed in asthma but may serve to sustain a
      given level of constriction. 

PMID- 25953838
TI  - The Legal Implications of HIPAA Privacy and Public Health Reporting for
      Correctional Facilities.
AB  - Inmates in cramped living quarters, a situation common to correctional
      facilities, are especially vulnerable to disease. Cramped living conditions,
      coupled with above-average rates of HIV, tuberculosis, and other communicable
      diseases, increase inmates' risk of problematic health outcomes. Thus, high
      quality health care and sustained efforts to prevent disease are especially
      important to improve inmate health within correctional facilities. Compliance
      with federal privacy restrictions pursuant to the Health Insurance Portability
      and Accountability Act (HIPAA) Privacy Rule and state disease reporting
      requirements will foster inmate health and assist efforts to prevent the spread
      of disease. This article examines the interplay between HIPAA rules and state
      reporting laws to preserve health information privacy and to control the spread
      of disease. 

PMID- 25953843
TI  - Concerning the Sixth Edition of Garriott's Medicolegal Aspects of Alcohol.

PMID- 25953844
TI  - Evaluating the validity of the French version of the Four-Dimensional Symptom
      Questionnaire with differential item functioning analysis.
AB  - BACKGROUND: GPs are daily confronted with mental disorders and psychosomatic
      problems. The Four-Dimensional Symptom Questionnaire (4DSQ), measuring distress,
      depression, anxiety and somatization, was purposively developed for primary care.
      It has been translated into 12 languages and is commonly used in several
      countries. It was translated into French in 2008, by forward and backward
      translation, but it has not been validated for a primary care population. AIM:
      This study aimed to establish whether the French 4DSQ measured the same
      constructs in the same way as the original Dutch 4DSQ. METHOD: Two samples of
      French general practice patients were recruited during routine care to obtain as
      much variability as possible. One sample included consecutive patients, from the
      waiting room of rural GPs, over a period of 2 weeks and the other sample included
      patients with suspected psychological problems or unexplained symptoms. This
      population was compared to a matched Dutch sample using confirmatory factor
      analysis (CFA) and differential item functioning (DIF) analysis. RESULTS: A total
      of 231 patients, from 15 French GPs, completed the questionnaire (Dutch reference
      group: 231). Mean age was 42.9 years (Dutch: 42.1); females numbered 71% in both
      samples. The multigroup CFA assessed configural invariance of one-factor models
      per 4DSQ scale. Thirteen of the total of 50 items in the 4DSQ, in three scales,
      were detected with DIF. However, DIF did not impact on the scale scores.
      CONCLUSION: French 4DSQ scales have the same latent structures and measure the
      same traits as the original Dutch 4DSQ.

PMID- 25953845
TI  - Prevalence and risk factors of epiretinal membrane in a cohort with
      cardiovascular disease risk, compared with the Blue Mountains Eye Study.
AB  - AIMS: To describe the prevalence of idiopathic and secondary epiretinal membranes
      (ERM) in a clinical cohort (Australian Heart Eye Study, AHES) and compare to the
      Blue Mountains Eye Study, and to determine whether associations exist between
      idiopathic ERM and the extent and severity of coronary artery disease (CAD).
      METHODS: The AHES is an observational study that surveyed 1680 participants who
      presented to a tertiary referral hospital for the evaluation of potential CAD by
      coronary angiography. Severity and extent of CAD was assessed using three scoring
      systems: (1) segment/vessel scores, (2) Gensini and (3) extent scores. Two types
      of ERM were identified: a more severe form, termed 'preretinal macular fibrosis'
      (PMF) in which retinal folds were identified; and a less severe form termed
      'cellophane macular reflex' (CMR), without visible retinal folds. RESULTS:
      Overall prevalence of ERM was 7.0% (n=115), with CMR and PMF each 3.5%. 72.7% of
      ERM cases were idiopathic (no secondary cause identified). Prevalence of PMF, but
      not CMR, was significantly higher than the corresponding age-standardised
      prevalence in the baseline Blue Mountains Eye Study (p<0.001). There was no
      significant association between extent and severity of CAD and idiopathic ERM.
      CONCLUSIONS: This study suggests that cardiovascular disease (specifically
      severity and extent of CAD) is not associated with ERM. However, there may be a
      greater prevalence of severe ERM (PMF) in a high cardiovascular risk cohort
      relative to a population-based cohort.

PMID- 25953847
TI  - Prevalence and determinants of undiagnosed diabetic retinopathy and vision
      threatening retinopathy in a multiethnic Asian cohort: the Singapore Epidemiology
      of Eye Diseases (SEED) study.
AB  - OBJECTIVE: To determine the prevalence and risk factors of undiagnosed diabetic
      retinopathy (DR), in particular vision-threatening DR (VTDR) in a multiethnic
      Asian cohort. DESIGN: A population-based survey of 3353 Chinese, 3280 Malays and
      3400 Indians (73.6% response) aged 40-80 years residing in Singapore. Diabetes
      mellitus (DM) was defined as random glucose >=11.1 mmol/L, use of diabetic
      medication or a previous physician diagnosis. DR severity was graded from retinal
      photographs following the modified Airlie House classification. VTDR was defined
      as the presence of severe non-proliferative DR (NPDR), proliferative DR (PDR) or
      clinically significant macular oedema (CSMO), using the Eye Diseases Prevalence
      Research Group definition. Participants were deemed 'undiagnosed' if they
      reported no prior physician diagnosis in structured interviews, in those with the
      condition. RESULTS: Of 10 033 participants, 2376 had DM (23.7%), of which 805
      (33.9%) had DR. Among 2376 with DM, 11.1% (n=263) were undiagnosed. Among 805
      with DR, 671 (83.3%) were undiagnosed. Among 212 with VTDR, 59 (27.3%) were
      undiagnosed. In multivariate models, factors associated with undiagnosed VTDR
      were higher low-density lipoprotein (LDL) cholesterol (OR=1.53, 95% CI 0.99 to
      2.35, p=0.05) and absence of visual impairment or blindness in any eye in terms
      of best-corrected vision OR=3.00, 95% CI 1.47 to 6.11, p=0.003). CONCLUSIONS: In
      this community, a quarter with VTDR is undiagnosed, and 8 in 10 with any DR are
      undiagnosed, compared with only 1 in 10 with DM undiagnosed. These findings
      suggest that screening for diabetes is successful, while screening for DR is
      currently inadequate in our population. Public health strategies to aid early
      diagnosis of DR in Singapore are urgently warranted to reduce blindness due to
      diabetes.

PMID- 25953846
TI  - PREGO (presentation of Graves' orbitopathy) study: changes in referral patterns
      to European Group On Graves' Orbitopathy (EUGOGO) centres over the period from
      2000 to 2012.
AB  - BACKGROUND/AIMS: The epidemiology of Graves' orbitopathy (GO) may be changing.
      The aim of the study was to identify trends in presentation of GO to tertiary
      centres and initial management over time. METHODS: Prospective observational
      study of European Group On Graves' Orbitopathy (EUGOGO) centres. All new
      referrals with a diagnosis of GO over a 4-month period in 2012 were included.
      Clinical and demographic characteristics, referral timelines and initial
      decisions about management were recorded. The data were compared with a similar
      EUGOGO survey performed in 2000. RESULTS: The demographic characteristics of 269
      patients studied in 2012 were similar to those collected in the year 2000,
      including smoking rates (40.0% vs 40.2%). Mild (60.5% vs 41.2%, p<0.01) and
      inactive GO (63.2% vs 39.9%, p<0.01) were more prevalent in 2012. The times from
      diagnosis of thyroid disease to being seen in EUGOGO centres (6 vs 16 months) and
      from first symptoms of GO (9 vs 16 months) or from diagnosis of GO (6 vs 12
      months) to first consultation in EUGOGO centres were shorter in 2012 (p<0.01).
      The initial management plans for GO were no different except surgical treatments
      for patients with mild inactive disease were more frequently offered in the 2012
      cohort than in 2000 (27.3% vs 17%, p<0.05), and selenium supplements were offered
      only in the 2012 cohort (21.2% vs 0%, p<0.01). CONCLUSIONS: These findings
      suggest that the clinical manifestations of patients with GO may be changing over
      time in Europe.

PMID- 25953848
TI  - Dual targeting of therapeutics to endothelial cells: collaborative enhancement of
      delivery and effect.
AB  - Anchoring pharmacologic agents to the vascular lumen has the potential to
      modulate critical processes at the blood-tissue interface, avoiding many of the
      off-target effects of systemically circulating agents. We report a novel strategy
      for endothelial dual targeting of therapeutics, which both enhances drug delivery
      and enables targeted agents to partner enzymatically to generate enhanced
      biologic effect. Based on the recent discovery that paired antibodies directed to
      adjacent epitopes of platelet endothelial cell adhesion molecule (PECAM)-1
      stimulate each other's binding, we fused single-chain fragments (scFv) of paired
      anti-mouse PECAM-1 antibodies to recombinant murine thrombomodulin (TM) and
      endothelial protein C receptor (EPCR), endothelial membrane proteins that partner
      in activation of protein C (PC). scFv/TM and scFv/EPCR bound to mouse endothelial
      PECAM-1 with high affinity (EC50 1.5 and 3.8 nM, respectively), and codelivery
      induced a 5-fold increase in PC activation not seen when TM and EPCR are anchored
      to distinct cell adhesion molecules. In a mouse model of acute lung injury, dual
      targeting reduces both the expression of lung inflammatory markers and trans
      endothelial protein leak by as much as 40%, as compared to either agent alone.
      These findings provide proof of principle for endothelial dual targeting, an
      approach with numerous potential biomedical applications.

PMID- 25953849
TI  - Proinsulin-producing, hyperglycemia-induced adipose tissue macrophages underlie
      insulin resistance in high fat-fed diabetic mice.
AB  - Adipose tissue macrophages (ATMs) play an important role in the pathogenesis of
      obese type 2 diabetes. High-fat diet (HFD)-induced obesity has been shown to lead
      to ATM accumulation in rodents; however, the impact of hyperglycemia on ATM
      dynamics in HFD-fed type 2 diabetic models has not been studied. We previously
      showed that hyperglycemia induces the appearance of proinsulin (PI)-producing
      proinflammatory bone marrow (BM)-derived cells (PI-BMDCs) in rodents. We fed a
      60% HFD to C57BL6/J mice to produce an obese type 2 diabetes model. Absent in
      chow-fed animals, PI-BMDCs account for 60% of the ATMs in the type 2 diabetic
      mice. The PI-ATM subset expresses TNF-alpha and other inflammatory markers, and
      is highly enriched within crownlike structures (CLSs). We found that amelioration
      of hyperglycemia by different hypoglycemic agents forestalled PI-producing ATM
      accumulation and adipose inflammation in these animals. We developed a diphtheria
      toxin receptor-based strategy to selectively ablate PI-BMDCs among ATMs.
      Application of the maneuver in HFD-fed type 2 diabetic mice was found to lead to
      near total disappearance of complex CLSs and reversal of insulin resistance and
      hepatosteatosis in these animals. In sum, we have identified a novel ATM subset
      in type 2 diabetic rodents that underlies systemic insulin resistance.

PMID- 25953850
TI  - Alternative activation of macrophages and pulmonary fibrosis are modulated by
      scavenger receptor, macrophage receptor with collagenous structure.
AB  - Alternative activation of alveolar macrophages is linked to fibrosis following
      exposure to asbestos. The scavenger receptor, macrophage receptor with
      collagenous structure (MARCO), provides innate immune defense against inhaled
      particles and pathogens; however, a receptor for asbestos has not been
      identified. We hypothesized that MARCO acts as an initial signaling receptor for
      asbestos, polarizes macrophages to a profibrotic M2 phenotype, and is required
      for the development of asbestos-induced fibrosis. Compared with normal subjects,
      alveolar macrophages isolated from patients with asbestosis express higher
      amounts of MARCO and have greater profibrotic polarization. Arginase 1 (40-fold)
      and IL-10 (265-fold) were higher in patients. In vivo, the genetic deletion of
      MARCO attenuated the profibrotic environment and pulmonary fibrosis in mice
      exposed to chrysotile. Moreover, alveolar macrophages from MARCO(-/-) mice
      polarize to an M1 phenotype, whereas wild-type mice have higher Ym1 (>3.0-fold)
      and nearly 7-fold more active TGF-beta1 in bronchoalveolar lavage (BAL) fluid
      (BALF). Arg(432) and Arg(434) in domain V of MARCO are required for the
      polarization of macrophages to a profibrotic phenotype as mutation of these
      residues reduced FIZZ1 expression (17-fold) compared with cells expressing MARCO.
      These observations demonstrate that a macrophage membrane protein regulates the
      fibrotic response to lung injury and suggest a novel target for therapeutic
      intervention.

PMID- 25953852
TI  - RAX2: a genome-wide detection method of condition-associated transcription
      variation.
AB  - Most mammalian genes have mRNA variants due to alternative promoter usage,
      alternative splicing, and alternative cleavage and polyadenylation. Expression of
      alternative RNA isoforms has been found to be associated with tumorigenesis,
      proliferation and differentiation. Detection of condition-associated
      transcription variation requires association methods. Traditional association
      methods such as Pearson chi-square test and Fisher Exact test are single test
      methods and do not work on count data with replicates. Although the Cochran
      Mantel Haenszel (CMH) approach can handle replicated count data, our simulations
      showed that multiple CMH tests still had very low power. To identify condition
      associated variation of transcription, we here proposed a ranking analysis of chi
      squares (RAX2) for large-scale association analysis. RAX2 is a nonparametric
      method and has accurate and conservative estimation of FDR profile. Simulations
      demonstrated that RAX2 performs well in finding condition-associated
      transcription variants. We applied RAX2 to primary T-cell transcriptomic data and
      identified 1610 (16.3%) tags associated in transcription with immune stimulation
      at FDR < 0.05. Most of these tags also had differential expression. Analysis of
      two and three tags within genes revealed that under immune stimulation short RNA
      isoforms were preferably used.

PMID- 25953851
TI  - The MEME Suite.
AB  - The MEME Suite is a powerful, integrated set of web-based tools for studying
      sequence motifs in proteins, DNA and RNA. Such motifs encode many biological
      functions, and their detection and characterization is important in the study of
      molecular interactions in the cell, including the regulation of gene expression.
      Since the previous description of the MEME Suite in the 2009 Nucleic Acids
      Research Web Server Issue, we have added six new tools. Here we describe the
      capabilities of all the tools within the suite, give advice on their best use and
      provide several case studies to illustrate how to combine the results of various
      MEME Suite tools for successful motif-based analyses. The MEME Suite is freely
      available for academic use at http://meme-suite.org, and source code is also
      available for download and local installation. 

PMID- 25953853
TI  - Structure of the nuclease subunit of human mitochondrial RNase P.
AB  - Mitochondrial RNA polymerase produces long polycistronic precursors that contain
      the mRNAs, rRNAs and tRNAs needed for mitochondrial translation. Mitochondrial
      RNase P (mt-RNase P) initiates the maturation of the precursors by cleaving at
      the 5' ends of the tRNAs. Human mt-RNase P is only active as a tripartite complex
      (mitochondrial RNase P proteins 1-3; MRPP1-3), whereas plant and trypanosomal
      RNase Ps (PRORPs)-albeit homologous to MRPP3-are active as single proteins. The
      reason for this discrepancy has so far remained obscure. Here, we present the
      crystal structure of human MRPP3, which features a remarkably distorted and hence
      non-productive active site that we propose will switch to a fully productive
      state only upon association with MRPP1, MRPP2 and pre-tRNA substrate. We suggest
      a mechanism in which MRPP1 and MRPP2 both deliver the pre-tRNA substrate and
      activate MRPP3 through an induced-fit process. 

PMID- 25953854
TI  - Human RNase P ribonucleoprotein is required for formation of initiation complexes
      of RNA polymerase III.
AB  - Human RNase P is implicated in transcription of small non-coding RNA genes by RNA
      polymerase III (Pol III), but the precise role of this ribonucleoprotein therein
      remains unknown. We here show that targeted destruction of HeLa nuclear RNase P
      inhibits transcription of 5S rRNA genes in whole cell extracts, if this precedes
      the stage of initiation complex formation. Biochemical purification analyses
      further reveal that this ribonucleoprotein is recruited to 5S rRNA genes as a
      part of proficient initiation complexes and the activity persists at
      reinitiation. Knockdown of RNase P abolishes the assembly of initiation complexes
      by preventing the formation of the initiation sub-complex of Pol III. Our results
      demonstrate that the structural intactness, but not the endoribonucleolytic
      activity per se, of RNase P is critical for the function of Pol III in cells and
      in extracts. 

PMID- 25953856
TI  - First insight into dead wood protistan diversity: a molecular sampling of bright
      spored Myxomycetes (Amoebozoa, slime-moulds) in decaying beech logs.
AB  - Decaying wood hosts a large diversity of seldom investigated protists.
      Environmental sequencing offers novel insights into communities, but has rarely
      been applied to saproxylic protists. We investigated the diversity of bright
      spored wood-inhabiting Myxomycetes by environmental sequencing. Myxomycetes have
      a complex life cycle culminating in the formation of mainly macroscopic fruiting
      bodies, highly variable in shape and colour that are often found on decaying
      logs. Our hypothesis was that diversity of bright-spored Myxomycetes would
      increase with decay. DNA was extracted from wood chips collected from 17 beech
      logs of varying decay stages from the Hainich-Dun region in Central Germany. We
      obtained 260 partial small subunit ribosomal RNA gene sequences of bright-spored
      Myxomycetes that were assembled into 29 OTUs, of which 65% were less than 98%
      similar to those in the existing database. The OTU richness revealed by molecular
      analysis surpassed that of a parallel inventory of fruiting bodies. We tested
      several environmental variables and identified pH, rather than decay stage, as
      the main structuring factor of myxomycete distribution.

PMID- 25953857
TI  - Construction of a Bacillus amyloliquefaciens strain for high purity levan
      production.
AB  - Bacillus amyloliquefaciens NK-1 has the potential to produce levan and poly-gamma
      glutamic acid (gamma-PGA) simultaneously. However, it is not possible to purify
      each single product from the same strain because the extraction process is
      identical. We deleted the pgs cluster (for gamma-PGA synthesis) from the NK-1
      strain and constructed a gamma-PGA-deficient NK-DeltaLP strain. Nuclear magnetic
      results showed that the NK-DeltaLP strain could produce high purity levan
      product. However, its levan titer was only 1.96 g L(-1) in the basal medium.
      Single-factor experimental and response surface methodology was used to optimize
      the culture condition, leading to levan titer of 13.9 and 22.6 g L(-1) in flask
      culture and in a 5-L bioreactor, respectively. The levan purity can reach to
      92.7% after 48 h cultivation. Furthermore, the relationship between levanase
      (LevB) and levan molecular weight was studied. The results showed that LevB
      resulted in the production of low molecular weight levan and its expression level
      determined the ratio of high and low molecular weight levan. We also deleted the
      sac cluster (for levan synthesis) from the NK-1 strain and constructed a levan
      deficient NK-L strain. The NK-L strain exhibited increased purity of gamma-PGA
      product from 79.5 to 91.2%.

PMID- 25953855
TI  - Efficient exploration of pan-cancer networks by generalized covariance selection
      and interactive web content.
AB  - Statistical network modeling techniques are increasingly important tools to
      analyze cancer genomics data. However, current tools and resources are not
      designed to work across multiple diagnoses and technical platforms, thus limiting
      their applicability to comprehensive pan-cancer datasets such as The Cancer
      Genome Atlas (TCGA). To address this, we describe a new data driven modeling
      method, based on generalized Sparse Inverse Covariance Selection (SICS). The
      method integrates genetic, epigenetic and transcriptional data from multiple
      cancers, to define links that are present in multiple cancers, a subset of
      cancers, or a single cancer. It is shown to be statistically robust and effective
      at detecting direct pathway links in data from TCGA. To facilitate interpretation
      of the results, we introduce a publicly accessible tool (cancerlandscapes.org),
      in which the derived networks are explored as interactive web content, linked to
      several pathway and pharmacological databases. To evaluate the performance of the
      method, we constructed a model for eight TCGA cancers, using data from 3900
      patients. The model rediscovered known mechanisms and contained interesting
      predictions. Possible applications include prediction of regulatory
      relationships, comparison of network modules across multiple forms of cancer and
      identification of drug targets.

PMID- 25953858
TI  - Older leaves of lettuce (Lactuca spp.) support higher levels of Salmonella
      enterica ser. Senftenberg attachment and show greater variation between plant
      accessions than do younger leaves.
AB  - Salmonella can bind to the leaves of salad crops including lettuce and survive
      for commercially relevant periods. Previous studies have shown that younger
      leaves are more susceptible to colonization than older leaves and that
      colonization levels are dependent on both the bacterial serovar and the lettuce
      cultivar. In this study, we investigated the ability of two Lactuca sativa
      cultivars (Saladin and Iceberg) and an accession of wild lettuce (L. serriola) to
      support attachment of Salmonella enterica serovar Senftenberg, to the first and
      fifth to sixth true leaves and the associations between cultivar-dependent
      variation in plant leaf surface characteristics and bacterial attachment.
      Attachment levels were higher on older leaves than on the younger ones and these
      differences were associated with leaf vein and stomatal densities, leaf surface
      hydrophobicity and leaf surface soluble protein concentrations. Vein density and
      leaf surface hydrophobicity were also associated with cultivar-specific
      differences in Salmonella attachment, although the latter was only observed in
      the older leaves and was also associated with level of epicuticular wax. 

PMID- 25953859
TI  - Corking the WEB and coiling through a jailed microcatheter: WEB assisted coiling,
      a useful technique avoiding the use of stents in treating wide-necked large
      intracranial aneurysms.
AB  - The WEB is an endovascular flow-disrupting device used in treating wide-necked
      intracranial aneurysms. Although the device is available in varying sizes, large
      aneurysms pose a challenge with the need for custom-made devices. We describe the
      use of coils as an adjunct to the WEB device in successfully treating large
      aneurysms in two patients, one with an acutely ruptured aneurysm. This novel
      technique of jailing a microcatheter, deploying the WEB and then coiling the
      aneurysm saves the need for intracranial stenting, thereby avoiding the need for
      antiplatelet therapy, which is of benefit in the setting of acute aneurysm
      rupture. 

PMID- 25953860
TI  - TB contracts: later deadline for some practices.

PMID- 25953861
TI  - Badger vaccination grant awarded.

PMID- 25953862
TI  - Enterprise awards for imaging company.

PMID- 25953863
TI  - Strong showing by UK vet schools in world rankings list.

PMID- 25953864
TI  - Veterinary relief efforts begin after Nepal earthquake.

PMID- 25953866
TI  - Recognition for police sniffer dog.

PMID- 25953865
TI  - Responsible use of antimicrobials in dry cows.

PMID- 25953867
TI  - Work-related stress and its impact on the veterinary profession.

PMID- 25953868
TI  - BSAVA certificate holders graduate.

PMID- 25953869
TI  - Dogs Trust awards for best EMS reports.

PMID- 25953870
TI  - More support for 'cat friendly clinics'.

PMID- 25953871
TI  - BSAVA presents its awards.

PMID- 25953872
TI  - Charolais calf diagnosed with idiopathic necrotising enteritis.

PMID- 25953873
TI  - Inherited disease in boxer dogs: a cautionary tale for molecular geneticists.

PMID- 25953874
TI  - One Health: a concept led by Africa, with global benefits.

PMID- 25953875
TI  - Dog identification: Getting ready for compulsory microchipping.

PMID- 25953876
TI  - Getting ready for compulsory microchipping.

PMID- 25953877
TI  - Detection of RHDV variant 2 in domestic rabbits in Azores.

PMID- 25953878
TI  - Lungworm in dogs.

PMID- 25953879
TI  - RCVS Council elections.

PMID- 25953880
TI  - RCVS Council elections.

PMID- 25953886
TI  - Collaborative dental skills teaching.

PMID- 25953887
TI  - First-year student diary.

PMID- 25953888
TI  - Lithium in drinking water and suicide mortality: interplay with lithium
      prescriptions.
AB  - BACKGROUND: Little is known about the effects of lithium intake through drinking
      water on suicide. This intake originates either from natural rock and soil
      elution and/or accumulation of lithium-based pharmaceuticals in ground water.
      AIMS: To examine the interplay between natural lithium in drinking water,
      prescribed lithium-based pharmaceuticals and suicide in Austria. METHOD: Spatial
      Bayesian regressions for males, females and pooled suicide mortality rates were
      estimated. RESULTS: Although the expected inverse association between lithium
      levels in drinking water and suicide mortality was confirmed for males and for
      total suicide rates, the relationship for females was not significant. The models
      do not indicate that lithium from prescriptions, assumed to accumulate in
      drinking water, is related to suicide risk patterns either as an individual
      effect or as a moderator of lithium levels in drinking water. Gender-specific
      differences in risk factors and local risk hot spots are confirmed. CONCLUSIONS:
      The findings do not support the hypotheses that lithium prescriptions have
      measureable protective effects on suicide or that they interact with lithium in
      drinking water.

PMID- 25953889
TI  - Duration of psychological therapy: relation to recovery and improvement rates in
      UK routine practice. [corrected].
AB  - BACKGROUND: Previous studies have reported similar recovery and improvement rates
      regardless of treatment duration among patients receiving National Health Service
      (NHS) primary care mental health psychological therapy. AIMS: To investigate
      whether this pattern would replicate and extend to other service sectors,
      including secondary care, university counselling, voluntary sector and workplace
      counselling. METHOD: We compared treatment duration with degree of improvement
      measured by the Clinical Outcomes in Routine Evaluation - Outcome Measure (CORE
      OM) for 26 430 adult patients who scored above the clinical cut-off point at the
      start of treatment, attended 40 or fewer sessions and had planned endings.
      RESULTS: Mean CORE-OM scores improved substantially (pre-post effect size 1.89);
      60% of patients achieved reliable and clinically significant improvement (RCSI).
      Rates of RCSI and reliable improvement and mean pre- and post-treatment changes
      were similar at all tested treatment durations. Patients seen in different
      service sectors showed modest variations around this pattern. CONCLUSIONS:
      Results were consistent with the responsive regulation model, which suggests that
      in routine care participants tend to end therapy when gains reach a good-enough
      level.

PMID- 25953890
TI  - Psychological coping and recurrent major adverse cardiac events following acute
      coronary syndrome.
AB  - BACKGROUND: Depressed mood and stress are associated with recurrent adverse
      outcomes following acute coronary syndrome (ACS), but the impact of psychological
      coping style has not been evaluated in detail. AIMS: We tested the relationship
      between task-oriented coping and event-free survival following ACS. METHOD: We
      followed 158 patients with ACS for an average of 59.8 months for major adverse
      cardiac outcomes. Psychological coping was assessed with the Coping Inventory of
      Stressful Situations. RESULTS: Compared with patients in the lower half of the
      distribution, those reporting higher task-oriented coping had a reduced hazard of
      adverse cardiac events (hazard ratio (HR) = 0.28, 95% CI 0.11-0.68, P = 0.005)
      independently of demographic, clinical and behavioural covariates. The
      combination of low task-oriented coping and high depressive symptoms showed a
      strong association with adverse outcomes (HR = 6.25, 95% CI 1.88-20.82, P =
      0.003). CONCLUSIONS: The tendency to cope using task-oriented strategies may
      promote event-free survival following ACS.

PMID- 25953891
TI  - Mortality associated with lithium and valproate treatment of US Veterans Health
      Administration patients with mental disorders.
AB  - BackgroundThe mood stabilisers lithium and valproate might plausibly have
      differing associations with mortality because of differing effects on mental
      health and various physiological indicators.AimsTo assess associations between
      lithium, valproate and non-suicide mortality.MethodIntention-to-treat, propensity
      score-matched cohort study.ResultsLithium was associated with significantly
      reduced non-suicide mortality in the intent-to-treat cohort over 0-90 days
      (hazard ratio (HR) = 0.67, 95% CI 0.51-0.87) but not longer. In secondary
      analyses, a sizeable reduction in mortality was observed during active treatment
      with lithium across all time periods studied (for example 365-day HR = 0.62, 95%
      CI 0.45-0.84), but significantly increased risks were observed among patients
      discontinuing lithium by 180 days (HR = 1.54, 95% CI 1.01
      2.37).ConclusionsPatients initiating lithium had lower non-suicide mortality over
      0-90 days than patients initiating valproate and consistently lower non-suicide
      mortality among patients maintaining treatment, but elevated risk among patients
      discontinuing treatment by 180 days. Although residual confounding or selection
      effects cannot be excluded, this study suggests potential benefits to enhancing
      lithium treatment persistence and the monitoring of patients discontinuing
      lithium. There is a need for further research. 

PMID- 25953892
TI  - Childhood sleep disturbance and risk of psychotic experiences at 18: UK birth
      cohort.
AB  - BACKGROUND: Sleep disturbances are commonly reported in the psychosis prodrome,
      but rarely explored in relation to psychotic experiences. AIMS: To investigate
      the relationship between specific parasomnias (nightmares, night terrors and
      sleepwalking) in childhood and later adolescent psychotic experiences. METHOD:
      The sample comprised 4720 individuals from a UK birth cohort. Mothers reported on
      children's experience of regular nightmares at several time points between 2 and
      9 years. Experience of nightmares, night terrors and sleepwalking was assessed
      using a semi-structured interview at age 12. Psychotic experiences were assessed
      at ages 12 and 18 using a semi-structured clinical interview. RESULTS: There was
      a significant association between the presence of nightmares at 12 and psychotic
      experiences at 18 when adjusted for possible confounders and psychotic
      experiences at 12 (OR = 1.62, 95% CI 1.19-2.20). The odds ratios were larger for
      those who reported persistent psychotic experiences. CONCLUSIONS: The presence of
      nightmares might be an early risk indicator for psychosis.

PMID- 25953893
TI  - Psychotic experiences and risk of death in the general population: 24-27 year
      follow-up of the Epidemiologic Catchment Area study.
AB  - BACKGROUND: Psychotic experiences are common in the general population and are
      associated with adverse psychiatric and social outcomes, even in the absence of a
      psychotic disorder. AIMS: To examine the association between psychotic
      experiences and mortality over a 24-27 year period. METHOD: We used data on 15
      049 adult participants from four sites of the Epidemiologic Catchment Area
      baseline survey in the USA in the early 1980s, linked to the National Death Index
      and other sources of vital status up until 2007. Psychotic experiences were
      assessed by the Diagnostic Interview Schedule. RESULTS: Lifetime psychotic
      experiences at baseline (n = 855; weighted prevalence, 5.5%) were significantly
      associated with all-cause mortality at follow-up after adjustment for
      sociodemographic characteristics and psychiatric diagnoses, including
      schizophrenia spectrum disorders (P<0.05). Baseline psychotic experiences were
      associated with over 5 years' shorter median survival time. Among the underlying
      causes of death, suicide had a particularly high hazard ratio (9.16, 95% CI 3.19
      26.29). CONCLUSIONS: Future research needs to explore the association of
      psychotic experiences with physical health and lifestyle factors that may mediate
      the relationship of psychotic experiences with mortality.

PMID- 25953894
TI  - 2-Amino-9H-pyrido[2,3-b]indole (AalphaC) Adducts and Thiol Oxidation of Serum
      Albumin as Potential Biomarkers of Tobacco Smoke.
AB  - 2-Amino-9H-pyrido[2,3-b]indole (AalphaC) is a carcinogenic heterocyclic aromatic
      amine formed during the combustion of tobacco. AalphaC undergoes bioactivation to
      form electrophilic N-oxidized metabolites that react with DNA to form adducts,
      which can lead to mutations. Many genotoxicants and toxic electrophiles react
      with human serum albumin (albumin); however, the chemistry of reactivity of
      AalphaC with proteins has not been studied. The genotoxic metabolites, 2
      hydroxyamino-9H-pyrido[2,3-b]indole (HONH-AalphaC), 2-nitroso-9H-pyrido[2,3
      b]indole (NO-AalphaC), N-acetyloxy-2-amino-9H-pyrido[2,3-b]indole (N-acetoxy
      AalphaC), and their [(13)C6]AalphaC-labeled homologues were reacted with albumin.
      Sites of adduction of AalphaC to albumin were identified by data-dependent
      scanning and targeted bottom-up proteomics approaches employing ion trap and
      Orbitrap MS. AalphaC-albumin adducts were formed at Cys(34), Tyr(140), and
      Tyr(150) residues when albumin was reacted with HONH-AalphaC or NO-AalphaC.
      Sulfenamide, sulfinamide, and sulfonamide adduct formation occurred at Cys(34)
      (AalphaC-Cys(34)). N-Acetoxy-AalphaC also formed an adduct at Tyr(332). Albumin
      AalphaC adducts were characterized in human plasma treated with N-oxidized
      metabolites of AalphaC and human hepatocytes exposed to AalphaC. High levels of N
      (deoxyguanosin-8-yl)-AalphaC (dG-C8-AalphaC) DNA adducts were formed in
      hepatocytes. The Cys(34) was the sole amino acid of albumin to form adducts with
      AalphaC. Albumin also served as an antioxidant and scavenged reactive oxygen
      species generated by metabolites of AalphaC in hepatocytes; there was a strong
      decrease in reduced Cys(34), whereas the levels of Cys(34) sulfinic acid (Cys
      SO2H), Cys(34)-sulfonic acid (Cys-SO3H), and Met(329) sulfoxide were greatly
      increased. Cys(34) adduction products and Cys-SO2H, Cys-SO3H, and Met(329)
      sulfoxide may be potential biomarkers to assess exposure and oxidative stress
      associated with AalphaC and other arylamine toxicants present in tobacco smoke. 

PMID- 25953895
TI  - A Novel Mutation in Isoform 3 of the Plasma Membrane Ca2+ Pump Impairs Cellular
      Ca2+ Homeostasis in a Patient with Cerebellar Ataxia and Laminin Subunit 1alpha
      Mutations.
AB  - The particular importance of Ca(2+) signaling to neurons demands its precise
      regulation within their cytoplasm. Isoform 3 of the plasma membrane Ca(2+) ATPase
      (the PMCA3 pump), which is highly expressed in brain and cerebellum, plays an
      important role in the regulation of neuronal Ca(2+). A genetic defect of the
      PMCA3 pump has been described in one family with X-linked congenital cerebellar
      ataxia. Here we describe a novel mutation in the ATP2B3 gene in a patient with
      global developmental delay, generalized hypotonia and cerebellar ataxia. The
      mutation (a R482H replacement) impairs the Ca(2+) ejection function of the pump.
      It reduces the ability of the pump expressed in model cells to control Ca(2+)
      transients generated by cell stimulation and impairs its Ca(2+) extrusion
      function under conditions of low resting cytosolic Ca(2+) as well. In silico
      analysis of the structural effect of the mutation suggests a reduced
      stabilization of the portion of the pump surrounding the mutated residue in the
      Ca(2+)-bound state. The patient also carries two missense mutations in LAMA1,
      encoding laminin subunit 1alpha. On the basis of the family pedigree of the
      patient, the presence of both PMCA3 and laminin subunit 1alpha mutations appears
      to be necessary for the development of the disease. Considering the observed
      defect in cellular Ca(2+) homeostasis and the previous finding that PMCAs act as
      digenic modulators in Ca(2+)-linked pathologies, the PMCA3 dysfunction along with
      LAMA1 mutations could act synergistically to cause the neurological phenotype. 

PMID- 25953896
TI  - Deletion of the PH-domain and Leucine-rich Repeat Protein Phosphatase 1 (Phlpp1)
      Increases Fibroblast Growth Factor (Fgf) 18 Expression and Promotes Chondrocyte
      Proliferation.
AB  - Endochondral ossification orchestrates formation of the vertebrate skeleton and
      is often induced during disease and repair processes of the musculoskeletal
      system. Here we show that the protein phosphatase Phlpp1 regulates endochondral
      ossification. Phlpp1 null mice exhibit decreased bone mass and notable changes in
      the growth plate, including increased BrdU incorporation and matrix production.
      Phosphorylation of known Phlpp1 substrates, Akt2, PKC, and p70 S6 kinase, were
      enhanced in ex vivo cultured Phlpp1(-/-) chondrocytes. Furthermore, Phlpp1
      deficiency diminished FoxO1 levels leading to increased expression of Fgf18,
      Mek/Erk activity, and chondrocyte metabolic activity. Phlpp inhibitors also
      increased matrix content, Fgf18 production and Erk1/2 phosphorylation. Chemical
      inhibition of Fgfr-signaling abrogated elevated Erk1/2 phosphorylation and
      metabolic activity in Phlpp1-null cultures. These results demonstrate that Phlpp1
      controls chondrogenesis via multiple mechanisms and that Phlpp1 inhibition could
      be a strategy to promote cartilage regeneration and repair. 

PMID- 25953897
TI  - Fatty Acid-binding Proteins Interact with Comparative Gene Identification-58
      Linking Lipolysis with Lipid Ligand Shuttling.
AB  - The coordinated breakdown of intracellular triglyceride (TG) stores requires the
      exquisitely regulated interaction of lipolytic enzymes with regulatory,
      accessory, and scaffolding proteins. Together they form a dynamic multiprotein
      network designated as the "lipolysome." Adipose triglyceride lipase (Atgl)
      catalyzes the initiating step of TG hydrolysis and requires comparative gene
      identification-58 (Cgi-58) as a potent activator of enzyme activity. Here, we
      identify adipocyte-type fatty acid-binding protein (A-Fabp) and other members of
      the fatty acid-binding protein (Fabp) family as interaction partners of Cgi-58.
      Co-immunoprecipitation, microscale thermophoresis, and solid phase assays proved
      direct protein/protein interaction between A-Fabp and Cgi-58. Using nuclear
      magnetic resonance titration experiments and site-directed mutagenesis, we
      located a potential contact region on A-Fabp. In functional terms, A-Fabp
      stimulates Atgl-catalyzed TG hydrolysis in a Cgi-58-dependent manner.
      Additionally, transcriptional transactivation assays with a luciferase reporter
      system revealed that Fabps enhance the ability of Atgl/Cgi-58-mediated lipolysis
      to induce the activity of peroxisome proliferator-activated receptors. Our
      studies identify Fabps as crucial structural and functional components of the
      lipolysome. 

PMID- 25953898
TI  - Stoichiometry of Heteromeric BAFF and APRIL Cytokines Dictates Their Receptor
      Binding and Signaling Properties.
AB  - The closely related TNF family ligands B cell activation factor (BAFF) and a
      proliferation-inducing ligand (APRIL) serve in the generation and maintenance of
      mature B-lymphocytes. Both BAFF and APRIL assemble as homotrimers that bind and
      activate several receptors that they partially share. However, heteromers of BAFF
      and APRIL that occur in patients with autoimmune diseases are incompletely
      characterized. The N and C termini of adjacent BAFF or APRIL monomers are
      spatially close and can be linked to create single-chain homo- or hetero-ligands
      of defined stoichiometry. Similar to APRIL, heteromers consisting of one BAFF and
      two APRILs (BAA) bind to the receptors B cell maturation antigen (BCMA),
      transmembrane activator and CAML interactor (TACI) but not to the BAFF receptor
      (BAFFR). Heteromers consisting of one APRIL and two BAFF (ABB) bind to TACI and
      BCMA and weakly to BAFFR in accordance with the analysis of the receptor
      interaction sites in the crystallographic structure of ABB. Receptor binding
      correlated with activity in reporter cell line assays specific for BAFFR, TACI,
      or BCMA. Single-chain BAFF (BBB) and to a lesser extent single-chain ABB, but not
      APRIL or single-chain BAA, rescued BAFFR-dependent B cell maturation in BAFF
      deficient mice. In conclusion, BAFF-APRIL heteromers of different stoichiometries
      have distinct receptor-binding properties and activities. Based on the
      observation that heteromers are less active than BAFF, we speculate that their
      physiological role might be to down-regulate BAFF activity. 

PMID- 25953899
TI  - The Neurexin/N-Ethylmaleimide-sensitive Factor (NSF) Interaction Regulates Short
      Term Synaptic Depression.
AB  - Although Neurexins, which are cell adhesion molecules localized predominantly to
      the presynaptic terminals, are known to regulate synapse formation and synaptic
      transmission, their roles in the regulation of synaptic vesicle release during
      repetitive nerve stimulation are unknown. Here, we show that nrx mutant synapses
      exhibit rapid short term synaptic depression upon tetanic nerve stimulation.
      Moreover, we demonstrate that the intracellular region of NRX is essential for
      synaptic vesicle release upon tetanic nerve stimulation. Using a yeast two-hybrid
      screen, we find that the intracellular region of NRX interacts with N
      ethylmaleimide-sensitive factor (NSF), an enzyme that mediates soluble NSF
      attachment protein receptor (SNARE) complex disassembly and plays an important
      role in synaptic vesicle release. We further map the binding sites of each
      molecule and demonstrate that the NRX/NSF interaction is critical for both the
      distribution of NSF at the presynaptic terminals and SNARE complex disassembly.
      Our results reveal a previously unknown role of NRX in the regulation of short
      term synaptic depression upon tetanic nerve stimulation and provide new
      mechanistic insights into the role of NRX in synaptic vesicle release. 

PMID- 25953900
TI  - The Wnt Inhibitor Sclerostin Is Up-regulated by Mechanical Unloading in
      Osteocytes in Vitro.
AB  - Although bone responds to its mechanical environment, the cellular and molecular
      mechanisms underlying the response of the skeleton to mechanical unloading are
      not completely understood. Osteocytes are the most abundant but least understood
      cells in bones and are thought to be responsible for sensing stresses and strains
      in bone. Sclerostin, a product of the SOST gene, is produced postnatally
      primarily by osteocytes and is a negative regulator of bone formation. Recent
      studies show that SOST is mechanically regulated at both the mRNA and protein
      levels. During prolonged bed rest and immobilization, circulating sclerostin
      increases both in humans and in animal models, and its increase is associated
      with a decrease in parathyroid hormone. To investigate whether SOST/sclerostin up
      regulation in mechanical unloading is a cell-autonomous response or a hormonal
      response to decreased parathyroid hormone levels, we subjected osteocytes to an
      in vitro unloading environment achieved by the NASA rotating wall vessel system.
      To perform these studies, we generated a novel osteocytic cell line (Ocy454) that
      produces high levels of SOST/sclerostin at early time points and in the absence
      of differentiation factors. Importantly, these osteocytes recapitulated the in
      vivo response to mechanical unloading with increased expression of SOST (3.4 +/-
      1.9-fold, p < 0.001), sclerostin (4.7 +/- 0.1-fold, p < 0.001), and the receptor
      activator of nuclear factor kappaBeta ligand (RANKL)/osteoprotegerin (OPG) (2.5
      +/- 0.7-fold, p < 0.001) ratio. These data demonstrate for the first time a cell
      autonomous increase in SOST/sclerostin and RANKL/OPG ratio in the setting of
      unloading. Thus, targeted osteocyte therapies could hold promise as novel
      osteoporosis and disuse-induced bone loss treatments by directly modulating the
      mechanosensing cells in bone. 

PMID- 25953901
TI  - Nuclear Receptor Nr4a2 Promotes Alternative Polarization of Macrophages and
      Confers Protection in Sepsis.
AB  - The orphan nuclear receptor Nr4a2 is known to modulate both inflammatory and
      metabolic processes, but the mechanism by which it regulates innate inflammatory
      homeostasis has not been adequately addressed. This study shows that exposure to
      ligands for Toll-like receptors (TLRs) robustly induces Nr4a2 and that this
      induction is tightly regulated by the PI3K-Akt signaling axis. Interestingly,
      exogenous expression of Nr4a2 in macrophages leads to their alternative phenotype
      with induction of genes that are prototypical M2 markers. Moreover, Nr4a2
      transcriptionally activates arginase 1 expression by directly binding to its
      promoter. Adoptive transfer experiments revealed that increased survival of
      animals in endotoxin-induced sepsis is Nr4a2-dependent. Thus our data identify a
      previously unknown role for Nr4a2 in the regulation of macrophage polarization. 

PMID- 25953902
TI  - Assembly Pathway of Hepatitis B Core Virus-like Particles from Genetically Fused
      Dimers.
AB  - Macromolecular complexes are responsible for many key biological processes.
      However, in most cases details of the assembly/disassembly of such complexes are
      unknown at the molecular level, as the low abundance and transient nature of
      assembly intermediates make analysis challenging. The assembly of virus capsids
      is an example of such a process. The hepatitis B virus capsid (core) can be
      composed of either 90 or 120 dimers of coat protein. Previous studies have
      proposed a trimer of dimers as an important intermediate species in assembly,
      acting to nucleate further assembly by dimer addition. Using novel genetically
      fused coat protein dimers, we have been able to trap higher-order assembly
      intermediates and to demonstrate for the first time that both dimeric and
      trimeric complexes are on pathway to virus-like particle (capsid) formation. 

PMID- 25953903
TI  - Coupling of Conformational Transitions in the N-terminal Domain of the 51-kDa
      FK506-binding Protein (FKBP51) Near Its Site of Interaction with the Steroid
      Receptor Proteins.
AB  - Interchanging Leu-119 for Pro-119 at the tip of the beta4-beta5 loop in the first
      FK506 binding domain (FK1) of the FKBP51 and FKBP52 proteins, respectively, has
      been reported to largely reverse the inhibitory (FKBP51) or stimulatory (FKBP52)
      effects of these co-chaperones on the transcriptional activity of glucocorticoid
      and androgen receptor-protein complexes. Previous NMR relaxation studies have
      identified exchange line broadening, indicative of submillisecond conformational
      motion, throughout the beta4-beta5 loop in the FK1 domain of FKBP51, which are
      suppressed by the FKBP52-like L119P substitution. This substitution also
      attenuates exchange line broadening in the underlying beta2 and beta3a strands
      that is centered near a bifurcated main chain hydrogen bond interaction between
      these two strands. The present study demonstrates that these exchange line
      broadening effects arise from two distinct coupled conformational transitions,
      and the transition within the beta2 and beta3a strands samples a transient
      conformation that resembles the crystal structures of the selectively inhibited
      FK1 domain of FKBP51 recently reported. Although the crystal structures for their
      series of inhibitors were interpreted as evidence for an induced fit mechanism of
      association, the presence of a similar conformation being significantly populated
      in the unliganded FKBP51 domain is more consistent with a conformational
      selection binding process. The contrastingly reduced conformational plasticity of
      the corresponding FK1 domain of FKBP52 is consistent with the current model in
      which FKBP51 binds to both the apo- and hormone-bound forms of the steroid
      receptor to modulate its affinity for ligand, whereas FKBP52 binds selectively to
      the latter state. 

PMID- 25953904
TI  - Coach development programmes to improve interpersonal coach behaviours: a
      systematic review using the re-aim framework.
AB  - OBJECTIVE: Although evidence supports the effectiveness of interpersonal Coach
      Development Programmes (CDPs), which are designed to foster coach-athlete
      relationships, an intervention's impact is shaped by numerous factors over and
      above effectiveness. The purpose of this systematic review was to examine the
      extent that published articles describing interpersonal CDP trials reported on
      indicators of internal and external validity, as conceptualised in the RE-AIM
      framework (ie, Reach, Effectiveness, Adoption, Implementation and Maintenance).
      METHODS: The search strategy was conducted according to the Preferred Reporting
      Items for Systematic Reviews and Meta-analyses guidelines, involving a database
      search and supplemental manual search of key articles and journals. After initial
      screening, the full-text search strategy involved identifying articles describing
      CDP trials and then selecting a specific subgroup of articles involving
      interpersonal CDP trials and excluding ineligible articles. Resulting trials were
      coded using a 47-item sport coaching adaptation of the RE-AIM coding sheet.
      RESULTS: 17 published articles met eligibility criteria, representing 10 distinct
      CDP trials. After attaining coder agreement, global ratings of RE-AIM indicators
      within interpersonal CDP trials ranged from the low to moderate quality. Whereas
      indicators of effectiveness and implementation were reported to some extent
      across all studies, maintenance within sport organisations and a number of
      specific indicators from across dimensions were rarely reported. CONCLUSIONS:
      These findings inform the future design and evaluation of CDPs that have the
      potential to be adopted in numerous settings and reach athletes and coaches who
      can most benefit.

PMID- 25953907
TI  - Corrigendum.

PMID- 25953905
TI  - The functional basis of wing patterning in Heliconius butterflies: the molecules
      behind mimicry.
AB  - Wing-pattern mimicry in butterflies has provided an important example of
      adaptation since Charles Darwin and Alfred Russell Wallace proposed evolution by
      natural selection >150 years ago. The neotropical butterfly genus Heliconius
      played a central role in the development of mimicry theory and has since been
      studied extensively in the context of ecology and population biology, behavior,
      and mimicry genetics. Heliconius species are notable for their diverse color
      patterns, and previous crossing experiments revealed that much of this variation
      is controlled by a small number of large-effect, Mendelian switch loci. Recent
      comparative analyses have shown that the same switch loci control wing-pattern
      diversity throughout the genus, and a number of these have now been positionally
      cloned. Using a combination of comparative genetic mapping, association tests,
      and gene expression analyses, variation in red wing patterning throughout
      Heliconius has been traced back to the action of the transcription factor optix.
      Similarly, the signaling ligand WntA has been shown to control variation in
      melanin patterning across Heliconius and other butterflies. Our understanding of
      the molecular basis of Heliconius mimicry is now providing important insights
      into a variety of additional evolutionary phenomena, including the origin of
      supergenes, the interplay between constraint and evolvability, the genetic basis
      of convergence, the potential for introgression to facilitate adaptation, the
      mechanisms of hybrid speciation in animals, and the process of ecological
      speciation.

PMID- 25953909
TI  - Patient Safety/Quality Improvement (PS/QI): Florence Nightingale prevails.

PMID- 25953910
TI  - Highlights from the current issue: May 2015.

PMID- 25953906
TI  - Mating and memory: an educational primer for use with "epigenetic control of
      learning and memory in Drosophila by Tip60 HAT action".
AB  - An article by Xu et al. in the December 2014 issue of GENETICS can be used to
      illustrate epigenetic modification of gene expression, reverse genetic
      manipulation, genetic/epigenetic influence on behavioral studies, and studies
      using the Drosophila model organism applied to human disease. This Primer
      provides background information; technical explanations of genetic, biochemical,
      and behavioral approaches from the study; and an example of an approach for
      classroom use with discussion questions to aid in student comprehension of the
      research article.

PMID- 25953911
TI  - Free flap reconstruction experience and outcomes at a low-volume institution over
      20 years.
AB  - OBJECTIVE: Assess the efficacy of free flap reconstruction performed at a low
      volume program and evaluate how volume and outcomes have changed over 20 years.
      STUDY DESIGN: Case series with chart review. SETTING: Tertiary academic medical
      center. SUBJECTS AND METHODS: A retrospective chart review was performed at a
      tertiary care academic program on all free tissue flaps from the primary
      reconstructive surgeon over 20 years (1993-2013). In total, 136 procedures were
      obtained from operative notes, billing codes, and chart databases. Outcome
      variables included procedure success and complications. Patients stayed in
      general intensive care unit and hospital floor units. RESULTS: Flap success was
      92.6% of all cases. In the past 13 years, 70 flaps were performed with 3 failures
      (96% success rate). Take-back rate was 16% of total cases with a flap recovery
      rate of 60%. Postoperative failure occurred after 72 hours in 60% of cases.
      Nearly 60% of patients experienced a complication of any type or severity. Twenty
      percent had a flap complication while maintaining viability, with half of these
      being partial dehiscence. Systemic complications affected 20% of all cases. The
      average hospital stay for noncomplicated patients was 13 days. There was 1
      postoperative mortality. Fibula and radial forearm were the most common flaps at
      44% and 26%, respectively. CONCLUSION: Free flap reconstruction of the head and
      neck can be performed by appropriately skilled surgeons with acceptable outcomes
      in low-volume settings. Success rate appears to increase as clinical experience
      is gained.

PMID- 25953912
TI  - Blood pressure after surgery among obese and nonobese children with obstructive
      sleep apnea.
AB  - OBJECTIVES: Treating obstructive sleep apnea in children is found to be
      associated with blood pressure decreases. However, exactly how adenotonsillectomy
      (T&A) affects blood pressure in obese and nonobese children remains unclear. This
      study assesses how obesity affects blood pressure in children with sleep apnea
      after T&A. STUDY DESIGN: Case series with chart review. SETTING: A tertiary
      referral center. SUBJECTS AND METHODS: From 2010 to 2012, a total of 78 children
      were included. Based on propensity score methods (age, sex, and preoperative
      apnea-hypopnea index matched), children were assigned to either the obese group
      (n = 39) or the nonobese group (n = 39). All children received
      adenotonsillectomy. We recorded clinical symptoms, preoperative overnight
      polysomnography (PSG), and subsequent PSG within 3 months after T&A. We measured
      blood pressure 3 times before PSG (nocturnal blood pressure) and after PSG
      (morning blood pressure) in a sleep laboratory. RESULTS: Following surgery, the
      nonobese group had a significantly decreased nocturnal diastolic blood pressure
      (DBP) index (-12.0 to -18.8, P = .018), morning systolic blood pressure (SBP;
      111.1 to 105.8 mm Hg, P = .014), SBP index (-5.4 to -10.9, P = .008), and DBP (
      12.0 to -18.7, P = .023). Nevertheless, all blood pressure parameters in the
      obese group were not significantly changed postoperatively. The nonobese group
      improved more than obese group in nocturnal and morning DBP and DBP index by 2
      way analysis of variance. CONCLUSION: Among the children receiving T&A as
      treatment for OSA, nonobese children improved more than obese children did in
      terms of blood pressure, allowing us to infer that obese children with OSA may
      benefit less from T&A in cardiovascular morbidities.

PMID- 25953913
TI  - Involvement of thioredoxin on the scaffold activity of NifU in heterocyst cells
      of the diazotrophic cyanobacterium Anabaena sp. strain PCC 7120.
AB  - The diazotrophic cyanobacterium Anabaena sp. strain PCC 7120 (A.7120)
      differentiates into specialized heterocyst cells that fix nitrogen under nitrogen
      starvation conditions. Although reducing equivalents are essential for nitrogen
      fixation, little is known about redox systems in heterocyst cells. In this study,
      we investigated thioredoxin (Trx) networks in Anabaena using TrxM, and identified
      16 and 38 candidate target proteins in heterocysts and vegetative cells,
      respectively, by Trx affinity chromatography (Motohashi et al. (Comprehensive
      survey of proteins targeted by chloroplast thioredoxin. Proc Natl Acad Sci USA,
      2001; 98: , 11224-11229)). Among these, the Fe-S cluster scaffold protein NifU
      that facilitates functional expression of nitrogenase in heterocysts was found to
      be a potential TrxM target. Subsequently, we observed that the scaffold activity
      of N-terminal catalytic domain of NifU is enhanced in the presence of Trx-system,
      suggesting that TrxM is involved in the Fe-S cluster biogenesis. 

PMID- 25953914
TI  - Cholesterol mobilization from hepatic lipid droplets during endotoxemia is
      altered in obese ob/ob mice.
AB  - The innate immune response to pathogens during the acute phase response includes
      lipid metabolism adaptations. Hepatic triacylglycerol (TG) and cholesteryl ester
      (CE) storage in and mobilization from lipid droplets (LDs) respond to metabolic
      changes under the control of liver X receptor (LXR) transactivation and cytokine
      transduction. To evaluate whether alterations of these mechanisms have an impact
      in the adaptive response to endotoxemia, we analysed liver metabolism changes in
      lipopolysaccharide (LPS)-treated ob/ob mice, which show altered metabolic and
      innate responses and a higher sensitivity to sepsis. Lipid composition of serum
      lipoproteins and hepatic LDs was determined in wild type and ob/ob mice 24 h
      after LPS treatment. Liver metabolic profiling was done by measuring enzyme
      activities and mRNA levels. Increased CE hydrolase activity in LDs from
      endotoxemic mice was accompanied by a lower content of CE and low or no induction
      of LXR-mediated expression of genes involved in HDL secretion. The attenuated
      response in liver lipid mobilization accompanied by the strain-specific
      cholesterol enrichment of secreted VLDL might lead to accumulation of LDL
      cholesterol. According to our findings, obese leptin-deficient mice present an
      altered control of hepatic lipid metabolism responses to LPS, which might be, in
      part at least, a consequence of impaired LXR. 

PMID- 25953915
TI  - Ferret airway epithelial cell cultures support efficient replication of influenza
      B virus but not mumps virus.
AB  - Ferrets have become the model animal of choice for influenza pathology and
      transmission experiments as they are permissive and susceptible to human
      influenza A viruses. However, inoculation of ferrets with mumps virus (MuV) did
      not lead to successful infections. We evaluated the use of highly differentiated
      ferret tracheal epithelium cell cultures, FTE, for predicting the potential of
      ferrets to support respiratory viral infections. FTE cultures supported
      productive replication of human influenza A and B viruses but not of MuV, whereas
      analogous cells generated from human airways supported replication of all three
      viruses. We propose that in vitro strategies using these cultures might serve as
      a method of triaging viruses and potentially reducing the use of ferrets in viral
      studies. 

PMID- 25953916
TI  - Identification and molecular characterization of a novel monopartite geminivirus
      associated with mulberry mosaic dwarf disease.
AB  - High-throughput sequencing of small RNAs allowed the identification of a novel
      DNA virus in a Chinese mulberry tree affected by a disease showing mosaic and
      dwarfing symptoms. Rolling-circle amplification and PCR with specific primers,
      followed by sequencing of eleven independent full-length clones, showed that this
      virus has a monopartite circular DNA genome (~ 2.95 kb) containing ORFs in both
      polarity strands, as reported previously for geminiviruses. A field survey showed
      the close association of the virus with diseased mulberries, so we tentatively
      named the virus mulberry mosaic dwarf-associated virus (MMDaV). The MMDaV genome
      codes for five and two putative proteins in the virion-sense and in the
      complementary-sense strands, respectively. Although three MMDaV virion-sense
      putative proteins did not share sequence homology with any protein in the
      databases, functional domains [coiled-coil and transmembrane (TM) domains] were
      identified in two of them. In addition, the protein containing a TM domain was
      encoded by an ORF located in a similar genomic position in MMDaV and in several
      other geminiviruses. As reported for members of the genera Mastrevirus and
      Becurtovirus, MMDaV replication-associated proteins are expressed through the
      alternative splicing of an intron, which was shown to be functional in vivo. A
      similar intron was found in the genome of citrus chlorotic dwarf-associated virus
      (CCDaV), a divergent geminivirus found recently in citrus. On the basis of
      pairwise comparisons and phylogenetic analyses, CCDaV and MMDaV appear to be
      closely related to each other, thus supporting their inclusion in a putative
      novel genus in the family Geminiviridae.

PMID- 25953918
TI  - Meet me in the middle: dual origins of dermal lymphatic vasculature in mammals.

PMID- 25953917
TI  - Mitochondrial antiviral-signalling protein plays an essential role in host
      immunity against human metapneumovirus.
AB  - Human metapneumovirus (hMPV) is a common cause of respiratory tract infection in
      the paediatrics population. Recently, we and others have shown that retinoic acid
      inducible gene 1 (RIG-I)-like receptors (RLRs) are essential for hMPV-induced
      cellular antiviral signalling. However, the contribution of those receptors to
      host immunity against pulmonary hMPV infection is largely unexplored. In this
      study, mice deficient in mitochondrial antiviral-signalling protein (MAVS), an
      adaptor of RLRs, were used to investigate the role(s) of these receptors in
      pulmonary immune responses to hMPV infection. MAVS deletion significantly
      impaired the induction of antiviral and pro-inflammatory cytokines and the
      recruitment of immune cells to the bronchoalveolar lavage fluid by hMPV. Compared
      with WT mice, mice lacking MAVS demonstrated decreased abilities to activate
      pulmonary dendritic cells (DCs) and abnormal primary T-cell responses to hMPV
      infection. In addition, mice deficient in MAVS had a higher peak of viral load at
      day 5 post-infection (p.i.) than WT mice, but were able to clear hMPV by day 7
      p.i. similarly to WT mice. Taken together, our data indicate a role of MAVS
      mediated pathways in the pulmonary immune responses to hMPV infection and the
      early control of hMPV replication. 

PMID- 25953919
TI  - Novel mechanism of transient outward potassium channel current regulation in the
      heart: implications for cardiac electrophysiology in health and disease.

PMID- 25953920
TI  - The iron paradigm of pulmonary arterial hypertension: Popeye knows best.

PMID- 25953921
TI  - Adrenergic and cholinergic plasticity in heart failure.

PMID- 25953922
TI  - PCSK9 Inhibition to Lower LDL-Cholesterol and Reduce Cardiovascular Risk: Great
      Expectations.

PMID- 25953923
TI  - Cholesterol efflux capacity as a novel biomarker for incident cardiovascular
      events: has high-density lipoprotein been resuscitated?

PMID- 25953924
TI  - Cold-Inducible RNA-Binding Protein Regulates Cardiac Repolarization by Targeting
      Transient Outward Potassium Channels.
AB  - RATIONALE: Cold-inducible RNA-binding protein (CIRP) is constitutively expressed
      at low levels across various tissues. It is rapidly upregulated by multiple
      stresses, underlying a general role for CIRP in organic adaptations to
      pathophysiological conditions. However, the role of CIRP in the heart remains
      unclear. OBJECTIVE: To examine the biofunctions of CIRP in the mammalian heart.
      METHODS AND RESULTS: Rats with targeted disruption of Cirp were generated using
      the TALEN (transcription activator-like effector nucleases)-based genome editing
      technique. The Cirp-knockout rats had structurally and functionally normal
      hearts. Resting ECG recordings revealed a short rate-corrected QT (QTc) interval
      in Cirp-null rats without any abnormalities in PR interval, RR interval or QRS
      waves as compared to wild-type animals. The shortened QTc interval from Cirp
      ablation was tightly linked to an abbreviated action potential duration in
      cardiac myocytes, which was attributable to increased transient outward potassium
      current (Ito). Furthermore, our findings uncovered that CIRP protein selectively
      bonded to KCND2 and KCND3 mRNAs encoding the functional alpha-subunits of Ito
      channel proteins. CIRP deficiency did not change the transcriptional activity of
      KCND2 or KCND3, but it facilitated their translation. Cirp knockout had no effect
      on the functional expression of ion channels other than Ito channels.
      CONCLUSIONS: CIRP modulates cardiac repolarization by negatively adjusting the
      expression and function of Ito channels. Our study may open a window to decipher
      the potential function of RNA-binding proteins in bioelectric activity.

PMID- 25953927
TI  - Letter by Neumann et al regarding article, "Myostatin regulates energy
      homeostasis in the heart and prevents heart failure".

PMID- 25953925
TI  - MicroRNAs and Cardiac Regeneration.
AB  - The human heart has a limited capacity to regenerate lost or damaged
      cardiomyocytes after cardiac insult. Instead, myocardial injury is characterized
      by extensive cardiac remodeling by fibroblasts, resulting in the eventual
      deterioration of cardiac structure and function. Cardiac function would be
      improved if these fibroblasts could be converted into cardiomyocytes. MicroRNAs
      (miRNAs), small noncoding RNAs that promote mRNA degradation and inhibit mRNA
      translation, have been shown to be important in cardiac development. Using this
      information, various researchers have used miRNAs to promote the formation of
      cardiomyocytes through several approaches. Several miRNAs acting in combination
      promote the direct conversion of cardiac fibroblasts into cardiomyocytes.
      Moreover, several miRNAs have been identified that aid the formation of inducible
      pluripotent stem cells and miRNAs also induce these cells to adopt a cardiac
      fate. MiRNAs have also been implicated in resident cardiac progenitor cell
      differentiation. In this review, we discuss the current literature as it pertains
      to these processes, as well as discussing the therapeutic implications of these
      findings. 

PMID- 25953928
TI  - Response to letter regarding article, "Myostatin regulates energy homeostasis in
      the heart and prevents heart failure".

PMID- 25953926
TI  - Molecular controls of arterial morphogenesis.
AB  - Formation of arterial vasculature, here termed arteriogenesis, is a central
      process in embryonic vascular development as well as in adult tissues. Although
      the process of capillary formation, angiogenesis, is relatively well understood,
      much remains to be learned about arteriogenesis. Recent discoveries point to the
      key role played by vascular endothelial growth factor receptor 2 in control of
      this process and to newly identified control circuits that dramatically influence
      its activity. The latter can present particularly attractive targets for a new
      class of therapeutic agents capable of activation of this signaling cascade in a
      ligand-independent manner, thereby promoting arteriogenesis in diseased tissues. 

PMID- 25953929
TI  - Mechanism and epidemiology of paediatric finger injuries at Prince of Wales
      Hospital in Hong Kong.
AB  - OBJECTIVES: To determine the mechanism and epidemiology of paediatric finger
      injuries in Hong Kong during 2003-2005 and 2010-2012. DESIGN: Comparison of two
      case series. SETTING: University-affiliated teaching hospital, Hong Kong.
      PATIENTS: This was a retrospective study of two cohorts of children (age, 0 to 16
      years) admitted to Prince of Wales Hospital with finger injuries during two 3
      year periods. Comparisons were made between the two groups for age, involved
      finger(s), mechanism of injury, treatment, and outcome. Telephone interviews were
      conducted for parents of children who sustained a crushing injury of finger(s) by
      door. RESULTS: A total of 137 children (group A) were admitted from 1 January
      2003 to 31 December 2005, and 109 children (group B) were admitted from 1 January
      2010 to 31 December 2012. Overall, the mechanisms and epidemiology of paediatric
      finger injuries were similar between groups A and B. Most finger injuries
      occurred in children younger than 5 years (group A, 56%; group B, 76%) and in
      their home (group A, 67%; group B, 69%). The most common mechanism was crushing
      injury of finger by door (group A, 33%; group B, 41%) on the hinge side (group A,
      63%; group B, 64%). The right hand was most commonly involved. The door was often
      closed by another child (group A, 37%; group B, 23%) and the injury often
      occurred in the presence of adults (group A, 60%; group B, 56%). Nailbed injury
      was the commonest type of injury (group A, 31%; group B, 39%). Fractures occurred
      in 24% and 23% in groups A and B, respectively. Traumatic finger amputation
      requiring replantation or revascularisation occurred in 12% and 10% in groups A
      and B, respectively. CONCLUSIONS: Crushing injury of finger by door is the most
      common mechanism of injury among younger children and accounts for a large number
      of hospital admissions. Serious injuries, such as amputations leading to
      considerable morbidity, can result. Crushing injury of finger by door occurs even
      in the presence of adults. There has been no significant decrease in the number
      of crushing injuries of finger by door in the 5 years between the two studies
      despite easily available and affordable preventive measures. It is the authors'
      view that measures aimed at promoting public awareness and education, and safety
      precautions are needed.

PMID- 25953930
TI  - Appropriate evaluation of ocular parameters in coronary artery bypass grafting
      surgery patients.

PMID- 25953931
TI  - [Prevalence of lower urinary tract symptoms among male population in Russian
      Federation: analysis of population study results].
AB  - The purpose of the present research is to study the incidence and severity of
      lower urinary tract symptoms (LUTS) in male population of the Russian Federation
      and to establish the relationship with the most common diseases. Based on the
      materials of population survey of 1083 men (mean age - 42,8+/-14,1 years) held in
      the Russian Federation in 2011-2012 the relationship between age, weight, height,
      sexual activity, addictions, co-morbidities and the answers to the questionnaire
      IPSS with the assessment of quality of life in relation with existing disorders
      of urination (QoL) was studied in six federal districts. 649 (59.9%) respondents
      had urinary system disorders (IPSS>0), the mean (+/-SD) of the sum IPSS
      questionnaire score was 5,0+/-7,0. LUTS severity was greater in: older men
      (tauB=0,441; p<0,001); in men who had undergone surgeries of the pelvic organs
      (tauB=0,242; p<0,001); in the presence of coronary artery ischaemic disease
      (tauB=0,242; p<0,001), arterial hypertension (tauB=0,255; p<0,001); diabetes
      mellitus (tauB=0,154; p<0,001); obesity (tauB=0,148; p<0,001); depression
      (tauB=0,126; p<0,001); and sexual disorders (tauB=-0,425; p<0,001). The
      prevalence of LUTS in men of the Russian Federation is high, their relationship
      with age and comorbidities require a comprehensive approach to prevention,
      diagnosis and treatment. 

PMID- 25953932
TI  - Prevention and treatment strategy in pregnant women with group B streptococcal
      infection.
AB  - Group B streptococcus (GBS; Streptococcus agalactiae) are encapsulated gram
      positive cocci belonging to Lancefield group B, that frequently colonizes the
      human genital and gastrointestinal tracts. It is an important cause of illness in
      three categories of population: infants, pregnant women, and adults with
      underlying medical conditions. In pregnant women and postpartum women, GBS is a
      frequent cause of asymptomatic bacteriuria, urinary tract infection, upper
      genital tract infection (i.e. intraamniotic infection or chorioamnionitis),
      postpartum endometritis (8%), pneumonia (2%), puerperal sepsis (2%), and
      bacteremia without a focal site (31%). It also can cause focal infections such as
      pneumonia, meningitis, and endocarditis, albeit rarely. Invasive maternal
      infection with GBS is associated with pregnancy loss and preterm delivery. Prior
      to the widespread use of maternal intrapartum chemoprophylaxis, maternal
      colonization with GBS conferred an increased risk of chorioamnionitis, and early
      postpartum infection. The serotype distribution of invasive GBS infection in
      pregnant women is similar to that of early-onset neonatal disease. The most
      common GBS serotypes causing invasive disease in adults and neonates are Ia, Ib,
      III, and V. Vaccination of adolescent women is considered an ideal solution.
      However, recent reports (April 2015) have shown that serotype IV GBS is emerging
      in pregnant carriers and causing infections in neonates and adults. This
      emergence is of concern because GBS conjugate vaccines that are being developed
      to prevent invasive disease may protect only against serotypes Ia, Ib, II, III,
      and V, or combinations thereof. Though research for the development of such a
      vaccine is underway, a good candidate vaccine has yet to surface. 

PMID- 25953933
TI  - [Treatment of medium and large post-operation ventral hernias with the usage of
      own tissues].
AB  - The authors have presented the method of treatment of medium and large post
      operation ventral hernias, which envisages reinforcement of front wall of the
      abdomen using its own tissues. For this purpose the authors used the hernial sac,
      which, after the appropriate processing is placed under the muscles of the front
      wall of the abdomen and is fixed to the outer oponeurosis with supporting suture.
      Apart from that, for the normalization of intra-abdominal pressure during the
      operation the authors monitor the pressure and in case of necessity apply
      weakening incisions on outer oponeurosis. Throughout the years of 2000-2012
      totally 90 operations have been implemented to the patient of both sex ageing
      from 22 to 82. Two cases of lethal outcome occurred in post-operation period due
      to heavy concomitant diseases. In distant period 40 patients have been examined.
      One patient was found to have relapse. Most of the patients practice heavy
      physical work. 

PMID- 25953934
TI  - [New technical approach to the treatment of large, gigantic, oblique inguinal
      hernias].
AB  - The authors suggest a method of hernioplasty for treatment of large and gigantic
      oblique inguinal hernias. The method envisages plasty of front wall of inguinal
      canal with lateral "excess" flap of abdominal external oblique muscle
      aponeurosis. According to the offered method the edges of the excess flap are
      sewn on to iliopubic cord, which first strengthens inguinal ligament before
      sewing to it of the edge of medial flap and then, after its redoubling, the flap
      is fastened to the surface of aponeurosis by means of interrupted suture. During
      12 year period 80 patients suffering from large and gigantic inguinal hernias
      were operated with the suggested method. In the post-operation period 8 (10,0%)
      complications occurred, one (1,2%) of them with lethal outcome. 30 patients were
      examined in the remote period. None of them had recurrence of the disease. 

PMID- 25953935
TI  - [Immunological aspects of delayed regeneration of mandibular fractures].
AB  - The level of complications in patients with the mandibular fractures does not
      have a tendency to the decline. A research purposes is a study of the basic laws
      of immunological reactions and possibility of optimizing processes osteogenesis
      by drugs-cytokines at patients with the mandibular fractures with delayed
      consolidation of bone tissue. 46 patients with the mandibular fractures were
      observed. The maintenance of cytokines IL - 1beta, TNF - alpha, IL - 4, SICAM-1
      in the blood serum, IgA, IgM, IgG in a mouth liquid was probed. It is set that in
      pathogenesis of delayed consolidation a basic role is played by changes
      reactivity of organism, which realized in three directions: immunodeficit of
      humoral immunity, immunodepression of cellular factors of defence, disbalance in
      functioning of the cytokines system. It is necessary to count the levels of
      products SICAM-1 and cytokine IL-1beta in the blood serum by the diagnostic
      criteria of bone repair features at patients with the mandibular fractures:
      development of delayed consolidation of mandibular fragments is accompanied the
      increase of their parameters at the control group more than in 2 and in 15 times
      (668,2+/-10,3 pg/ml and 363,4 +/-6,6 pg/ml relatively). Includding in the complex
      treatment of the mandibular fractures of immunomodulator Ronkoleukin showed
      clinico-immunological efficiency for the patients with impaired bone repair. 

PMID- 25953936
TI  - Early repolarization, localization of J point elevation on ECG and arrhythmias.
AB  - Final aim of this observational study was to determine correlation between
      localization of J point elevation and number of premature ventricular beats. The
      52 patients (19-68 years old; 31 men and 21 women) were divided in two groups
      based on localization of J point elevation. First Group - 9 patients (5 men and 4
      women) with J-point elevation >=1 mm in >=2 contiguous inferior and/or lateral
      leads on a standard 12-lead ECG reading, Second Group - other 43 (26 men and 17
      women) patients with another localization of J point elevation. Total summarized
      number of premature ventricular contractions for each group was compared and
      analyzed. The results of the study shows that the number of premature ventricular
      beats in first group was 61% higher. Thus, in our opinion J-point elevation >=1
      mm in >=2 contiguous inferior and/or lateral leads, is more arrhythmogenic. Data
      shows that this difference is statistically significant. 

PMID- 25953937
TI  - Prevalence of self-reported food allergy in different age groups of georgian
      population.
AB  - Epidemiological studies in high income countries suggested that a big proportion
      of the population in Europe and America report adverse reactions to food. Self
      reported prevalence of food allergy varied from 1.2% to 17% for milk, 0.2% to 7%
      for egg, 0% to 2% for peanuts and fish, 0% to 10% for shellfish, and 3% to 35%
      for any food. The aim of our study was to report the prevalence of self-reported
      food allergy in the different age groups of Georgian population and to reveal the
      most common self-reported food allergens. ISAAC phase III study methodology and
      questionnaires were used for data collection. Questions about food allergy were
      added to the survey and involved questions about self-reported food allergy. 6-7
      years old 6140 children (response rate-94,5%) and 13-14 years old 5373
      adolescents (response rate-86,9%) from two locations of Georgia, Tbilisi and
      Kutaisi were surveyed. 500 randomly assessed adults from Tbilisi aged 18 years
      and older were added later (response rate-97,6%). Findings revealed that self
      reported food allergy among 6-7 years old age group and 13-14 years old age were
      almost the same (15,7% and 15,9% correspondingly) and slightly lower in adult
      population - 13,9%. Study revealed, that hen's egg was the commonest implicated
      food for 6-7 years age group, hazel nut - for 13-14 years old age group followed
      by hen's egg. Walnut and hazel nut were most reported foods for adult population.
      The findings also revealed that food allergy is one of the most important risk
      factor for symptoms associated with asthma (OR-3,05; 95%CI 2.50-3.74),
      rhinoconjunctivitis (OR-2,85; 95%CI 2.24-3.64) and eczema (OR-5,42; 95%CI 4.08
      7.18) in childhood. The data has provided the first epidemiological information
      related to food allergy among children and adults in Georgia. Results should
      serve as baseline information for food allergy screening, diagnosis and
      treatment. Our findings can also inform the public health officials on the
      disease burden and may offer some recommendations for minimizing the allergy
      related risks. 

PMID- 25953938
TI  - [The efficacy of ivabradine in chronic heart failure (review)].
AB  - This review article is devoted to the treatment of chronic heart failure (HF)
      with a new generation drug - ivabradine. It is well known that HF is one of the
      most frequent reason of high mortality worldwide. HF is characterised by cardiac
      remodeling, which is central in the pathophysiology of HF including hemodynamic,
      neurohumoral and neurohormonal mechanisms during its development and established
      prognostic factor in patients suffered with this disease. Despite the
      introduction in medical practice of many drugs for the treatment of chronic HF
      the lethal outcome associated with HF remains high nowadays, which can be
      explained by complexity of remodeling mechanisms characteristic for development
      of HF. Ivabradine that has been introduced in medical practice in last decade is
      a pure heart rate-slowing agent. A large number of studies in patients with
      cardiovascular disease have demonstrated that heart rate (HR) is a very important
      and major independent risk factor for prognosis, because lowering of HR reduces
      cardiac work and diminished myocardial oxygen requirement. It was shown that
      ivabradine a selective inhibitor of the hyperpolarisation activated sodium chanel
      (If) is involved in pacemaker generation and responsiveness of the sino-atrial
      node resulting in HR reduction without negative inotropic action. Ivabradine in
      chronic HF improves diastolic function and attenuates cardiac tissue hypoxia.
      Long-term reduction of HR induced by ivabradine reduced remodeling and preserved
      nitric oxide (NO) bioavailability, resulting from processes triggered early after
      reduction of HR. The complex therapy including ivabradine promotes HR fall,
      leading in reduction of attacks of a stable angina and improved quality of life.
      Ivabradine may target the endothelial NO production via inhibition of protein
      tyrosine phosphatase 1B leading to endothelial protection. HR reduction by
      ivabradine reduces oxidative stress, improves endothelial function and prevents
      development of atherosclerostic changes in apolipoprotein E-deficient mice. In
      multicenter clinical trials it has been proved that ivabradine is superior to
      beta-blocking agents during complex therapy of chronic HF accompanied with its
      beneficial effects related to cardiac remodeling, improvement of the currency of
      HF and diminution of patients rehospitalisation. It is suggested that ivabradine
      as a newer agent is a valuable perspective drug for the treatment of congestive
      HF. 

PMID- 25953939
TI  - Association of anti-phospholipasea2-receptor antibodies with clinical course of
      idiopathic membranous nephropathy.
AB  - Aim of the study - assessment of the presence of M-type phospholipase A2 receptor
      antibodies in Georgian patients with biopsy proven IMN and their correlation with
      the disease activity for the appliance and monitoring of immunosuppressive
      therapy. A total 37 patients, after exclusion of the possible secondary factors,
      with biopsy proven IMN entered the study. All patients received standard
      immunosuppressive therapy: cyclosporine combined with methylprednisolone. There
      were 28 (76%) patients with PLA2R-AB positive and 9 (24%) negative (assessed as
      1:<10) at baseline. Among the 28 patients under immunosuppressive therapy at
      month 6 in 11 of them PLA2R-AB turned negative, in 14 decreased quantitatively
      but were persistent positive and in 3 of them PLA2R-AB once turned negative then
      relapsed after withdrawn of immunosuppressive therapy. Among 11 PLA2R-AB negative
      patients, 9 patients got complete remission of proteinuria and the other 2
      patients only partial remission. At month 12 the range of proteinuria was
      significantly lower in PLA2R-AB negative group than in PLA2R-AB positive group.
      The level of circulating PLA2R-AB in IMN patients showed correlation with disease
      activity. The indicators of good prognosis of IMN were negative PLA2R-AB titer at
      baseline and progressive decreasing of titer under the immunosuppressive therapy
      in PLA2R-AB positive patients. The detection and measurement of PLA2R-AB in INM
      patients may be important tool in monitoring of the disease and efficacy of the
      treatment. 

PMID- 25953940
TI  - Single center experience in successful prevention of exit-site infection in
      patients on peritoneal dialysis.
AB  - The aim of our study was to use non-cytotoxic, easily available agent - 3% NaCl
      (hypertonic) saline compresses as prophylaxis measure for long-term prevention of
      ESI and avoid antibiotic resistance later. Advantages of hypertonic saline
      include excellent patient acceptance, ease of use, lack of adverse effects on
      exit site, adjacent skin, catheter or systemic reaction, and minimal expense.
      During the observational time of 36 months a total of 78 patients were enrolled
      in this study. Patients were randomized into three groups: in group A 36
      patients, were using 3% saline compresses as ESI prophylaxis 3 times weekly,
      group B 22 patients were using mupirocine 2% ointment 3 times weekly as exit-site
      dressing and group C 30 patients were using no aseptic agents for exit-site care.
      Group A showed the minimal rate of ESI compare to groups B and C. None of the
      tunnel infections was complicated with peritonitis and catheter loss. The use
      hypertonic saline compresses as routinely daily or three times weekly exit-site
      care has a promising results for long-term catheter related infection
      prophylaxis. 

PMID- 25953941
TI  - Humoral immunity status if infertile men antisperm antibodies and various
      pathologies of reproductive organs.
AB  - The aim of the research was to study humoral immunity status of infertile men
      with high concentration of antisperm antibodies in blood plasma, sexually
      transmitted diseases (STD) and various pathologies of reproductive system.
      Analysis of 496 outpatient cards has been conducted. It was found, that patients
      with high levels of ASA >150 mg/l, or average 100-150 mg/l, had statistically
      significant (p=0,001) high content of Ig A and Ig G relative to the control
      group. Men with serum ASA concentration >100 mg/l, had statistically
      insignificant increased levels of all 3 types of immunoglobulins relative to the
      control group. Patients infected with Chlamydia trachomatis proved to have
      decreased IgA and IgG, 0,95+/-0,12 and 6,64+/-0,5 respectively (p<0,001). As for
      the patients infected with Ureaplasma urealyticum, decreased levels in Ig A and
      Ig M have been reported as 0,75+/-0,29 and 1,08+/-0,08 respectively (p<0,05). In
      the course of prostate gland inflammation statistically significant deficiency of
      Ig A and IgG was evident relative to the control group, 0,75+/-0,10 g/l and
      5,94+/-0,54 g/l respectively (p<0,001). As for the males with varicocele, Ig A
      and Ig M decrease is noticeable relative to the control group, 1,06+/-0,21 g/l
      and 0,61+/-0,19 g/l respectively (p<0,05). 

PMID- 25953942
TI  - [The strategic psychotherapy in the treatment of mental and behavioral disorders
      of the anxiety spectrum].
AB  - The aim of the work is to present the results of psychotherapeutic treatment of
      patients with anxiety disorders in the model of short-term strategic therapy. On
      the basis of the material the effectiveness of the short-term strategic approach
      is represented in the treatment of patients with phobic disorders. The apparent
      non-directive behavior of therapist allows to bypass the internal resistance of
      the patient. As a result of using the paradoxical prescriptions, phobic
      manifestations lost or significantly reduced their symptomatic significance. The
      combination of the neurolinguistic techniques and strategic approach gave to the
      psychotherapeutic process high effectiveness. 

PMID- 25953943
TI  - Physical culture as the basis of students' healthy lifestyle.
AB  - The present study aimed at investigation of the relationship between
      physiological features of cardiorespiratory system of a group of athletes with
      individually-typological charac-teristics of the organism (age, type of
      constitution, sports experience, the degree of adaptation) to physical activities
      on the basis of a comprehensive study of the cardiorespiratory system. The study
      was conducted on 450 students from 18 to 24 years of age from Kazakhstan, Russia,
      India, and Pakistan to evaluate the influence of physical culture and sports on
      the formation of a healthy lifestyle of young people in higher education
      institutions. The students were divided into groups - the first group - student
      18-20 years of age; the second group - students 21-24 years of age; the control
      group included students of the same age not actively involved in sports (2
      lessons of physical training per week). The relationship between physiological
      features of cardiorespiratory system of athletes and individually-typological
      characteristics of the organism (age, type of constitution, sports experience,
      the degree of adaptation) was determined. 

PMID- 25953944
TI  - [Erythrocyte membrane abnormalities - hereditary elliptocytosis].
AB  - This study was designed to investigate the 4 year old boy with Hereditary
      Elliptocitosis (HE). The diagnosis of this rare hemolytic anemia was based on
      detailed family history (positive in the 4-th generation), physical examination
      and Para-clinical data analyses. The vast majority of patients with HE are
      asymptomatic, severe forms are rare. The most important is examination of blood
      films, which is helpful to detect the morphology abnormalities of red cells. In
      case of HE a different approach is required. Positive family history and series
      of investigations should be conducted to determine the HE. 

PMID- 25953945
TI  - Application of nano composites in the fixation and processing of histological
      material.
AB  - The pathological examination is one of the longest in the list of medical tests.
      Most of this time is spent on preparation of the microslide, which involves the
      following phases: fixation, processing, cutting and staining. Our objective was
      to develop optimal regime of fixation and processing (namely, 1 and 2 stage of
      processing) by applying Nano composites for the development of quick, cheap and
      qualitative protocol of material processing. 24 various types and concentration
      Nano composite fixation device were used in study, made by applying single-layer,
      surface modified carbon nanotubes in the conditions of ultrasound treatment by
      UP200HT device. Also was developed Nano tubular network integration method in bio
      material in the conditions of ultrasound treatment, when besides Nano composite
      fixation devices various Nano composite reagents (namely, 0.003% and 0.005% Nano
      composite alcohols) were used in material processing. There were carried out 126
      experiments in sum and experiments were checked through standard processing.
      Fixation devices produced from formalin and alcohol base showed good result of
      fixation - by using them in the conditions of ultrasound treatment, practically
      24 times decreased the period of fixation (as a standard of fixation was applied
      minimal rate of ASCO/Cap guideline dated by 2008 - 6 hours). The best way was
      considered Nano composite fixation device of NH2 functionalization of the 0.002%
      concentration on alcohol base A19 (according to the fixation rate 15 minutes with
      ultrasound maintenance). Nano tubular network integration method enabled us to
      have decreased the number of alcohols of ascending concentration and delay time
      in them. High time efficiency factor - Tk = 47.5% (time of new processing/
      standard processing time X100) and high efficiency factor of the expense of
      reagents - Rk = 33% (number of reagents spent at the time of new
      processing/number of spent reagents at the time of standard processing X100) is
      obtained as a result of Nano integrated processing, so almost 2 times less time
      is spent and 1/3 times less reagents needed. 

PMID- 25953946
TI  - [Analysis of some species of magnolia introduced to west georgia, on content of
      aporphine alkaloids and their biological activity].
AB  - The goal of research was study of vegetative organs of Magnolia species
      introduced to west Georgia on qualitative and quantitative content of aporphine
      alkaloids and evaluate cytotoxic activity of total alkaloids from M. officinalis
      and M. glauca against A-549, DLD-1 and WS-1. Qualitative and quantitative content
      of aporphine alkaloids in different vegetative organs were determined by
      chromatographic methods. Based on the researches alkaloids - liriodenine and
      lanuginozine are characteristic for leaves, for bark of branches - liriodenine, d
      caaverine; for bark of trunk - a liriodenine, a caaverine and a magnoflorine.
      Liriodenine may be considered as is chemotaxonomic sign of genus Magnolia, as it
      was found in all analyzed vegetative organs. In vitro cytotoxic activity of total
      alkaloids of M. officinalis and M. glauca has been investigated against DLD-1, WS
      1 and A-549. Total alkaloids of M. glauca expressed significant cytotoxic
      activity against DLD-1 and WS-1, and medium cytotoxicity against A-549; M.
      officinalis exerted middle activity against A-549, DLD-1, WS-1. 

PMID- 25953947
TI  - [Alterations in populations of T-lymphocytes in the rats blood during
      experimental preeclampsia].
AB  - Immune tolerance to the fetus is predetermined mainly by HLA-G expression in
      trophoblasts, varying the ratio of Th1 / Th2, decrease in the content of
      cytotoxic T lymphocytes and natural killer cells (NK cells) and fusion "tread" of
      antibodies. The aim of the study was to establish the role of the placental
      hypoxia in regulation of expression of -lymphocytes populations in the blood of
      rats at different stages of pregnancy. For the purpose of modeling of PE in
      pregnant rats, at10-th day of gestation the lumen of the abdominal aorta below
      the renal artery was narrowed by the silk thread a third of its diameter (0.2
      mm). In blood serum was defined the relative content of leukocyte subpopulations
      by indirect immunofluorescence in cytotoxic assay using monoclonal antibodies to
      CD4, CD8, CD14, CD16 leukocytes ("ICN Pharmaceutical", USA). The study found that
      in the blood of animals of control group (phisiological pregnancy) within the 2nd
      3rd trimester of gestation of CD4, CD8 subpopulations of lymphocytes did not
      change. The animals of the experimental group (pregnancy complicated by placental
      hypoxia) content of CD8 subpopulations and CD16 (NK cells) in the blood did not
      change significantly compared with those in the blood of animals in the control
      group, whereas CD4 T cell subpopulation in the second and in the third trimester
      statistical significantly decreased compared with those in control group
      (p<0.001). The ratio of immunoregulatory subpopulations lymphocytes CD4/CD8
      decreased, number of CD14 (monocytes) phenotypes leukocytes increased. It is
      concluded that the placental hypoxia promotes disorder of the regulation of the
      immune balance of the mother's body during pregnancy, which is manifested in
      decrease ratio immunoregulatory subpopulations of lymphocyte, increasing the
      intensity of local expression of monocytes. 

PMID- 25953948
TI  - You call it "self-exuberance"; I call it "bragging": miscalibrated predictions of
      emotional responses to self-promotion.
AB  - People engage in self-promotional behavior because they want others to hold
      favorable images of them. Self-promotion, however, entails a trade-off between
      conveying one's positive attributes and being seen as bragging. We propose that
      people get this trade-off wrong because they erroneously project their own
      feelings onto their interaction partners. As a consequence, people overestimate
      the extent to which recipients of their self-promotion will feel proud of and
      happy for them, and underestimate the extent to which recipients will feel
      annoyed (Experiments 1 and 2). Because people tend to promote themselves
      excessively when trying to make a favorable impression on others, such efforts
      often backfire, causing targets of self-promotion to view self-promoters as less
      likeable and as braggarts (Experiment 3). 

PMID- 25953949
TI  - The origins of counting algorithms.
AB  - Humans' ability to count by verbally labeling discrete quantities is unique in
      animal cognition. The evolutionary origins of counting algorithms are not
      understood. We report that nonhuman primates exhibit a cognitive ability that is
      algorithmically and logically similar to human counting. Monkeys were given the
      task of choosing between two food caches. First, they saw one cache baited with
      some number of food items, one item at a time. Then, a second cache was baited
      with food items, one at a time. At the point when the second set was
      approximately equal to the first set, the monkeys spontaneously moved to choose
      the second set even before that cache was completely baited. Using a novel
      Bayesian analysis, we show that the monkeys used an approximate counting
      algorithm for comparing quantities in sequence that is incremental, iterative,
      and condition controlled. This proto-counting algorithm is structurally similar
      to formal counting in humans and thus may have been an important evolutionary
      precursor to human counting. 

PMID- 25953950
TI  - Tyrosine-derived polycarbonate scaffolds for bone regeneration in a rabbit radius
      critical-size defect model.
AB  - The aim of the study was to determine bone regeneration in a rabbit radius
      critical-size defect (CSD) model using a specific polymer composition (E1001(1k))
      from a library of tyrosine-derived polycarbonate scaffolds coated with a calcium
      phosphate (CP) formulation (E1001(1k) + CP) supplemented with recombinant human
      bone morphogenetic protein-2 (rhBMP-2). Specific doses of rhBMP-2 (0, 17, and 35
      MUg/scaffold) were used. E1001(1k) + CP scaffolds were implanted in unilateral
      segmental defects (15 mm length) in the radial diaphyses of New Zealand White
      rabbits. At 4 and 8 weeks post-implantation, bone regeneration was determined
      using micro-computed tomography (uCT), histology, and histomorphometry. The
      quantitative outcome data suggest that E1001(1k) + CP scaffolds with rhBMP-2 were
      biocompatible and promoted bone regeneration in segmental bone defects.
      Histological examination of the implant sites showed that scaffolds made of
      E1001(1k) + CP did not elicit adverse cellular or tissue responses throughout
      test periods up to 8 weeks. Noteworthy is that the incorporation of a very small
      amount of rhBMP-2 into the scaffolds (as low as 17 MUg/defect site) promoted
      significant bone regeneration compared to scaffolds consisting of E1001(1k) + CP
      alone. This finding indicates that E1001(1k) + CP may be an effective platform
      for bone regeneration in a critical size rabbit radius segmental defect model,
      requiring only a minimal dose of rhBMP-2. 

PMID- 25953953
TI  - Silk fibroin aerogels: potential scaffolds for tissue engineering applications.
AB  - Silk fibroin (SF) is a natural protein, which is derived from the Bombyx mori
      silkworm. SF based porous materials are extensively investigated for biomedical
      applications, due to their biocompatibility and biodegradability. In this work,
      CO2 assisted acidification is used to synthesize SF hydrogels that are
      subsequently converted to SF aerogels. The aqueous silk fibroin concentration is
      used to tune the morphology and textural properties of the SF aerogels. As the
      aqueous fibroin concentration increases from 2 to 6 wt%, the surface area of the
      resultant SF aerogels increases from 260 to 308 m(2) g(-1) and the compressive
      modulus of the SF aerogels increases from 19.5 to 174 kPa. To elucidate the
      effect of the freezing rate on the morphological and textural properties, SF
      cryogels are synthesized in this study. The surface area of the SF aerogels
      obtained from supercritical CO2 drying is approximately five times larger than
      the surface area of SF cryogels. SF aerogels exhibit distinct pore morphology
      compared to the SF cryogels. In vitro cell culture studies with human foreskin
      fibroblast cells demonstrate the cytocompatibility of the silk fibroin aerogel
      scaffolds and presence of cells within the aerogel scaffolds. The SF aerogels
      scaffolds created in this study with tailorable properties have potential for
      applications in tissue engineering. 

PMID- 25953952
TI  - The landscape of genomic imprinting across diverse adult human tissues.
AB  - Genomic imprinting is an important regulatory mechanism that silences one of the
      parental copies of a gene. To systematically characterize this phenomenon, we
      analyze tissue specificity of imprinting from allelic expression data in 1582
      primary tissue samples from 178 individuals from the Genotype-Tissue Expression
      (GTEx) project. We characterize imprinting in 42 genes, including both novel and
      previously identified genes. Tissue specificity of imprinting is widespread, and
      gender-specific effects are revealed in a small number of genes in muscle with
      stronger imprinting in males. IGF2 shows maternal expression in the brain instead
      of the canonical paternal expression elsewhere. Imprinting appears to have only a
      subtle impact on tissue-specific expression levels, with genes lacking a
      systematic expression difference between tissues with imprinted and biallelic
      expression. In summary, our systematic characterization of imprinting in adult
      tissues highlights variation in imprinting between genes, individuals, and
      tissues. 

PMID- 25953954
TI  - National and regional trends in equity within specialised health care in Finland
      in 2002-2010.
AB  - AIMS: Equity is an important goal of health-care systems. Nevertheless, previous
      research indicates that health-care systems do not deliver health services
      equitably and that socio-economic differences in both health and health-care use
      may even be increasing. The aim of this study was to investigate national and
      regional time trends in equity within specialised health care in Finland.
      METHODS: The data used in the study were obtained from the Hospital Discharge
      Register covering all hospital admissions in Finland from 2002 to 2010 for
      patients having utilised specialised non-psychiatric inpatient care. Income data
      were individually linked to these register data. Equity was measured in terms of
      concentration index at hospital district level. RESULTS: Concentration indices
      across hospital districts and years were negative, suggesting specialised
      inpatient care to be distributed pro poor. Overall, the concentration indices
      remained fairly stable during the study period. However, a drop in the indices
      appeared in all hospital districts between 2005 and 2008, and a reverse
      development was found after 2008. In internal medicine departments of the
      hospital districts, the distribution of the indices was more pro poor compared to
      surgery but the trends within both specialties were similar to those within
      specialised care in general. CONCLUSIONS: The pro-poor distribution of
      concentration indices is consistent with morbidity differences the introduction
      of the waiting time guarantee in 2005, which brought along an increment in
      resources, as well as the launch of new regulations and financial incentives,
      probably increased access to specialised health care among low-income patients
      temporarily.

PMID- 25953955
TI  - Bone regeneration and gene expression in bone defects under healthy and
      osteoporotic bone conditions using two commercially available bone graft
      substitutes.
AB  - Biosilicate((r)) and Bio-Oss((r)) are two commercially available bone
      substitutes, however, little is known regarding their efficacy in osteoporotic
      conditions. The purpose of this study was to evaluate the osteogenic properties
      of both materials, at tissue and molecular level. Thirty-six Wistar rats were
      submitted to ovariectomy (OVX) for inducing osteoporotic conditions and sham
      surgery (SHAM) as a control. Bone defects were created in both femurs, which were
      filled with Biosilicate((r)) or Bio-Oss((r)), and empty defects were used as
      control. For the healthy condition both Biosilicate((r)) and Bio-Oss((r)) did not
      improve bone formation after 4 weeks. Histomorphometric evaluation of
      osteoporotic bone defects with bone substitutes showed more bone formation,
      significant for Bio-Oss((r)). Molecular biological evaluation was performed by
      gene-expression analysis (Runx-2, ALP, OC, OPG, RANKL). The relative gene
      expression was increased with Biosilicate((r)) for all genes in OVX rats and for
      Runx-2, ALP, OC and RANKL in SHAM rats. In contrast, with Bio-Oss((r)), the
      relative gene expression of OVX rats was similar for all three groups. For SHAM
      rats it was increased for Runx-2, ALP, OC and RANKL. Since both materials
      improved bone regeneration in osteoporotic conditions, our results suggest that
      bone defects in osteoporotic conditions can be efficiently treated with these two
      bone substitutes. 

PMID- 25953956
TI  - Biological modeling of gold nanoparticle enhanced radiotherapy for proton
      therapy.
AB  - Gold nanoparticles (GNPs) have shown potential as a radiosensitizer for radiation
      therapy using photon beams. Recently, experimental studies have been carried out
      using proton beams showing the GNP enhanced responses in proton therapy. In this
      work, we established a biological model to investigate the change in survival of
      irradiated cells due to the radiosensitizing effect of gold nanoparticles.
      Results for proton, megavoltage (MV) photon and kilovoltage (kV) photon beams are
      compared. For each particle source, we assessed various treatment depths, GNP
      cellular uptakes and sizes. We showed that kilovoltage photons caused the highest
      enhancement due to the high interaction probability between GNPs and kV photons.
      The cell survival fraction can be significantly reduced for both proton and MV
      photon irradiations if GNPs accumulate in the cell. For instance, the sensitizer
      enhancement ratio (SER) is 1.33 for protons in the middle of a spread out Bragg
      peak for 1 uM of internalized 50 nm GNPs. If the GNPs can all be internalized
      into the cell nucleus, the SER for proton therapy increases from 1.33 to 1.81.
      The results also show that for the same mass of GNPs in the cells, one can expect
      the greatest sensitization by smaller GNPs, i.e. a SER of 1.33 for 1 uM of
      internalized 50 nm GNPs and a SER of 3.98 for the same mass of 2 nm GNPs. We
      concluded that if the GNPs cannot be internalized into the cytoplasm, no GNP
      enhancement will be observed for proton treatment. Meanwhile, proton radiotherapy
      can potentially be enhanced with GNPs if they can be internalized into cells, and
      especially the cell nucleus. 

PMID- 25953951
TI  - Contrasting genetic architectures in different mouse reference populations used
      for studying complex traits.
AB  - Quantitative trait loci (QTLs) are being used to study genetic networks, protein
      functions, and systems properties that underlie phenotypic variation and disease
      risk in humans, model organisms, agricultural species, and natural populations.
      The challenges are many, beginning with the seemingly simple tasks of mapping
      QTLs and identifying their underlying genetic determinants. Various specialized
      resources have been developed to study complex traits in many model organisms. In
      the mouse, remarkably different pictures of genetic architectures are emerging.
      Chromosome Substitution Strains (CSSs) reveal many QTLs, large phenotypic
      effects, pervasive epistasis, and readily identified genetic variants. In
      contrast, other resources as well as genome-wide association studies (GWAS) in
      humans and other species reveal genetic architectures dominated with a relatively
      modest number of QTLs that have small individual and combined phenotypic effects.
      These contrasting architectures are the result of intrinsic differences in the
      study designs underlying different resources. The CSSs examine context-dependent
      phenotypic effects independently among individual genotypes, whereas with GWAS
      and other mouse resources, the average effect of each QTL is assessed among many
      individuals with heterogeneous genetic backgrounds. We argue that variation of
      genetic architectures among individuals is as important as population averages.
      Each of these important resources has particular merits and specific applications
      for these individual and population perspectives. Collectively, these resources
      together with high-throughput genotyping, sequencing and genetic engineering
      technologies, and information repositories highlight the power of the mouse for
      genetic, functional, and systems studies of complex traits and disease models. 

PMID- 25953957
TI  - Random-effects meta-analysis: the number of studies matters.
AB  - This paper investigates the impact of the number of studies on meta-analysis and
      meta-regression within the random-effects model framework. It is frequently
      neglected that inference in random-effects models requires a substantial number
      of studies included in meta-analysis to guarantee reliable conclusions. Several
      authors warn about the risk of inaccurate results of the traditional DerSimonian
      and Laird approach especially in the common case of meta-analysis involving a
      limited number of studies. This paper presents a selection of likelihood and non
      likelihood methods for inference in meta-analysis proposed to overcome the
      limitations of the DerSimonian and Laird procedure, with a focus on the effect of
      the number of studies. The applicability and the performance of the methods are
      investigated in terms of Type I error rates and empirical power to detect
      effects, according to scenarios of practical interest. Simulation studies and
      applications to real meta-analyses highlight that it is not possible to identify
      an approach uniformly superior to alternatives. The overall recommendation is to
      avoid the DerSimonian and Laird method when the number of meta-analysis studies
      is modest and prefer a more comprehensive procedure that compares alternative
      inferential approaches. R code for meta-analysis according to all of the
      inferential methods examined in the paper is provided.

PMID- 25953958
TI  - XSim: Simulation of Descendants from Ancestors with Sequence Data.
AB  - Real or imputed high-density SNP genotypes are routinely used for genomic
      prediction and genome-wide association studies. Many researchers are moving
      toward the use of actual or imputed next-generation sequence data in whole-genome
      analyses. Simulation studies are useful to mimic complex scenarios and test
      different analytical methods. We have developed the software tool XSim to
      efficiently simulate sequence data in descendants in arbitrary pedigrees. In this
      software, a strategy to drop-down origins and positions of chromosomal segments
      rather than every allele state is implemented to simulate sequence data and to
      accommodate complicated pedigree structures across multiple generations. Both C++
      and Julia versions of XSim have been developed. 

PMID- 25953960
TI  - Seeing a cause for blindness in severe pancreatitis.

PMID- 25953959
TI  - Major Histocompatibility Complex Genes Map to Two Chromosomes in an
      Evolutionarily Ancient Reptile, the Tuatara Sphenodon punctatus.
AB  - Major histocompatibility complex (MHC) genes are a central component of the
      vertebrate immune system and usually exist in a single genomic region. However,
      considerable differences in MHC organization and size exist between different
      vertebrate lineages. Reptiles occupy a key evolutionary position for
      understanding how variation in MHC structure evolved in vertebrates, but
      information on the structure of the MHC region in reptiles is limited. In this
      study, we investigate the organization and cytogenetic location of MHC genes in
      the tuatara (Sphenodon punctatus), the sole extant representative of the early
      diverging reptilian order Rhynchocephalia. Sequencing and mapping of 12 clones
      containing class I and II MHC genes from a bacterial artificial chromosome
      library indicated that the core MHC region is located on chromosome 13q. However,
      duplication and translocation of MHC genes outside of the core region was
      evident, because additional class I MHC genes were located on chromosome 4p. We
      found a total of seven class I sequences and 11 class II beta sequences, with
      evidence for duplication and pseudogenization of genes within the tuatara
      lineage. The tuatara MHC is characterized by high repeat content and low gene
      density compared with other species and we found no antigen processing or MHC
      framework genes on the MHC gene-containing clones. Our findings indicate
      substantial differences in MHC organization in tuatara compared with mammalian
      and avian MHCs and highlight the dynamic nature of the MHC. Further sequencing
      and annotation of tuatara and other reptile MHCs will determine if the tuatara
      MHC is representative of nonavian reptiles in general. 

PMID- 25953961
TI  - Retention, transfer out and loss to follow-up two years after delivery in a
      cohort of HIV+ pregnant women in Malawi.
AB  - In this study, we analysed in a cohort of pregnant women followed for two years
      the proportion of women remaining at the same clinic, those who transferred to
      other clinics, and those lost to follow-up. The possible determinants of the loss
      to follow-up were also assessed in a setting of postpartum discontinuation based
      on CD4+ count. A total of 311 pregnant women received antiretroviral therapy from
      week 25 of gestational age until six months postpartum (end of breastfeeding
      period), or indefinitely if meeting the criteria for treatment (baseline CD4+
      <350 cells/mm(3)). Twenty-four months after delivery, six women had died, 247
      were in active follow-up, 21 had transferred to another antiretroviral therapy
      clinic and 37 were lost to follow-up (rate of loss to follow-up 13%, 95% CI 9.1
      16.9%). The presence of a baseline CD4+ count above 350 cells/mm(3) was
      associated with a ten-fold higher risk of loss to follow-up after six months of
      delivery (hazard ratio: 9.8, 95% CI 2.2-42.7, for baseline CD4 >350 cells/mm(3)
      versus baseline CD4+ count below 350 cells/mm(3), p = 0.002). This finding
      suggests that discontinuation of drugs when the risk of transmission has ceased
      can have a negative impact on the retention in care of these women.

PMID- 25953962
TI  - Gonococcal tenosynovitis in two HIV-infected heterosexual men: delayed diagnoses
      following negative urine nucleic acid amplification testing.
AB  - With recent increases in annual gonorrhoea incidence and disproportionately high
      infection rates amongst men who have sex with men, the clinical picture of
      disseminated gonococcal infection is changing. We present two cases where
      consideration of, and investigation for, disseminated Neisseria gonorrhoeae
      infection provided the answer when routine inpatient diagnostics had been
      unsuccessful.

PMID- 25953964
TI  - Sexually acquired Salmonella Typhi urinary tract infection.
AB  - We report a case of isolated urinary Salmonella enterica serotype Typhi in an HIV
      positive man who has sex with men. He was clinically well and blood and stool
      cultures were negative, indicating that this may have been a sexually acquired
      urinary tract infection.

PMID- 25953965
TI  - Tolerance of Superficial Dose to Setup Error With Tomotherapy: Is a Skin Flash
      Tool Required?
AB  - BACKGROUND: In cancers of the head and neck, gross tumor or areas at risk of
      microscopic disease often lie close to the skin, while the skin itself may not be
      at risk. With intensity-modulated radiotherapy, setup errors can lead to
      underdosage of superficial structures because the collimator will not by default
      open beyond the skin surface to apply coverage in the air overlying the skin.
      Thus, small setup errors can move superficial structures out of field for some
      beams. Some planning systems allow for manually extrapolating fluence for beams
      tangential to superficial targets. It is unclear whether this problem is
      significant with tomotherapy. METHODS: A head and neck phantom was utilized. A 3
      mm bolus was used to represent the skin and allow placement of dosimeters at 3 mm
      depth. Thermoluminescent dosimeters were placed at reproducible points on the
      skin surface and at 3 mm depth. The phantom was irradiated, with the target
      volume deep to the thermoluminescent dosimeters receiving a dose of 5 Gy. This
      process was repeated with the phantom displaced 2.5 mm and again with a
      displacement of 5 mm. These displacements simulated setup errors that in clinical
      practice would correspond to bending or twisting of the neck that could not be
      corrected with rotations or translations. RESULTS: When the phantom was displaced
      2.5 mm, the dose measured at 3 mm depth was 99.2% (95.9%-102.5%) of the control.
      With a 5-mm displacement, the dose at 3 mm only dropped to 91.1% (88.8%-93.4%) of
      the control. Dose measured at skin surface decreased to a greater degree with
      such setup error. CONCLUSIONS: Dose at superficial depths degraded only slightly
      with 2.5-mm and even 5-mm displacements. With the tomotherapy system, superficial
      dose appears to be robust to clinically relevant setup errors. However, if the
      skin is at risk, bolus should be used to ensure adequate coverage.

PMID- 25953963
TI  - Lifetime suicide attempt history, quality of life, and objective functioning
      among HIV/AIDS patients with alcohol and illicit substance use disorders.
AB  - This cross-sectional study evaluated lifetime prevalence of suicide attempts in
      170 HIV/AIDS patients with substance use disorders and the impact of suicide
      attempt history on subjective indices of quality of life and objective indices of
      cognitive and physical functioning. All patients met the diagnostic criteria for
      past-year cocaine or opioid use disorders and 27% of patients also had co
      occurring alcohol use disorders. Compared to their counterparts without a history
      of a suicide attempt, patients with a history of a suicide attempt (n = 60,
      35.3%) had significantly poorer emotional and cognitive quality of life scores
      (ps < .05), but not physical, social, or functional/global quality-of-life
      scores. Lifetime suicide attempt status was unrelated to objective indices of
      cognitive functioning, but there was a non-significant trend (p = .07) toward
      lower viral loads in those with a lifetime suicide attempt relative to those
      without. The findings indicate that suicide attempt histories are prevalent among
      HIV/AIDS patients with substance use disorders and relate to poorer perceived
      emotional and cognitive quality of life, but not objective functioning. HIV/AIDS
      patients with substance use disorders should be screened for lifetime histories
      of suicide attempts and offered assistance to improve perceived emotional and
      cognitive functioning. 

PMID- 25953966
TI  - Primary health care research in Bolivia: systematic review and analysis.
AB  - Bolivia is currently undergoing a series of healthcare reforms centred around the
      Unified Family, Community and Intercultural Health System (SAFCI), established in
      2008 and Law 475 for Provision of Comprehensive Health Services enacted in 2014
      as a first step towards universal health coverage. The SAFCI model aims to
      establish an intercultural, intersectoral and integrated primary health care
      (PHC) system, but there has not been a comprehensive analysis of effective
      strategies towards such an end. In this systematic review, we analyse research
      into developing PHC in Bolivia utilizing MEDLINE, the Virtual Health Library and
      grey literature from Pan American Health Organization/World Health Organization's
      internal database. We find that although progress has been made towards
      implementation of a healthcare system incorporating principles of PHC, further
      refining the system and targeting improvements effectively will require increased
      research and evaluation. Particularly in the 7 years since establishment of
      SAFCI, there has been a dearth of PHC research that makes evaluation of such key
      national policies impossible. The quantity and quality of PHC research must be
      improved, especially quasi-experimental studies with adequate control groups. The
      infrastructure for such studies must be strengthened through improved financing
      mechanisms, expanded institutional capacity and setting national research
      priorities. Important for future progress are improved tracking of health
      indicators, which in Bolivia are often out-of-date or incomplete, and
      prioritization of focused national research priorities on relevant policy issues.
      This study aims to serve as an aid towards PHC development efforts at the
      national level, as well as provide lessons for countries globally attempting to
      build effective health systems accommodating of a multi-national population in
      the midst of development.

PMID- 25953967
TI  - Microhaematuria as a diagnostic marker of Schistosoma haematobium in an
      outpatient clinical setting: results from a cross-sectional study in rural Ghana.
AB  - The utility of microhaematuria (as measured by urine reagent strips) as a
      surrogate marker for Schistosoma haematobium infection is not established in
      patients with urogenital symptoms presenting to clinical settings, although
      previous studies have demonstrated its utility in screening asymptomatic
      individuals in large community or school-based settings. In this cross-sectional
      study of 201 patients, multivariate analysis demonstrated microhaematuria as an
      independent predictor of S. haematobium infection (OR, 4.29; 95% CI, 1.6-11.9) in
      individuals presenting with urogenital symptoms to an outpatient medical
      department (OPD) at a rural Ghanaian medical center. Microhaematuria is
      predictive of S. haematobium infections in clinical settings in endemic regions. 

PMID- 25953968
TI  - Antithrombotic therapy after transcatheter aortic valve implantation.

PMID- 25953969
TI  - Dyspnoea on exertion in a 15-year-old boy.

PMID- 25953970
TI  - Relationship between altitude and the prevalence of hypertension in Tibet: a
      systematic review.
AB  - INTRODUCTION: Hypertension is a leading cause of cardiovascular disease, which is
      the cause of one-third of global deaths and is a primary and rising contributor
      to the global disease burden. The objective of this systematic review was to
      determine the prevalence and awareness of hypertension among the inhabitants of
      Tibet and its association with altitude, using the data from published
      observational studies. METHODS: We conducted electronic searches in Medline,
      Embase, ISI Web of Science and Global Health. No gender or language restrictions
      were imposed. We assessed the methodological characteristics of included studies
      using the Strengthening the Reporting of Observational Studies in Epidemiology
      (STROBE) criteria. Two reviewers independently determined the eligibility of
      studies, assessed the methodology of included studies and extracted the data. We
      used meta-regression to estimate the degree of change in hypertension prevalence
      with increasing altitude. RESULTS: We identified 22 eligible articles of which
      eight cross-sectional studies with a total of 16 913 participants were included.
      The prevalence of hypertension ranged between 23% and 56%. A scatter plot of
      altitude against overall prevalence revealed a statistically significant
      correlation (r=0.68; p=0.04). Meta-regression analysis revealed a 2% increase in
      the prevalence of hypertension with every 100 m increase in altitude (p=0.06).
      The locations and socioeconomic status of subjects affected the awareness and
      subsequent treatment and control of hypertension. CONCLUSIONS: The results from
      cross-sectional studies suggest that there is a significant correlation between
      altitude and the prevalence of hypertension among inhabitants of Tibet. The
      socioeconomic status of the inhabitants can influence awareness and management of
      hypertension. Very little research into hypertension has been conducted in other
      prefectures of Tibet where the altitude is much higher. Further research
      examining the impact of altitude on blood pressure is warranted.

PMID- 25953971
TI  - Home-based diabetes symptom self-management education for Mexican Americans with
      type 2 diabetes.
AB  - This pilot study evaluated an innovative diabetes symptom awareness and self
      management educational program for Mexican Americans, a fast growing minority
      population experiencing a diabetes epidemic. Patients with diabetes need
      assistance interpreting and managing symptoms, which are often annoying and
      potentially life-threatening. A repeated measures randomized controlled trial was
      conducted with 72 Mexican Americans aged 25-75 years with type 2 diabetes.
      Experimental condition participants received eight weekly, in-home, one-on-one
      educational and behavior modification sessions with a registered nurse focusing
      on symptom awareness, glucose self-testing and appropriate treatments, followed
      by eight biweekly support telephone sessions. Wait-listed control condition
      participants served as comparisons at three time points. Hierarchical linear
      modeling was used to evaluate the effects of the intervention between- and within
      groups on psychosocial, behavioral and clinical outcomes. Participants were
      predominantly female, middle-aged, moderately acculturated and in poor glycemic
      control. Experimental group participants (n = 39) significantly improved glycemic
      control, blood pressure, symptoms, knowledge, self-efficacy, empowerment and
      quality of life. Post intervention focus groups reported satisfaction with the
      symptom focus. Addressing symptoms led to clinical and psychosocial improvements.
      Symptoms seem to be an important motivator and a useful prompt to engage patients
      in diabetes self-management behaviors to relieve symptoms and prevent
      complications. 

PMID- 25953972
TI  - Physical activity, physical fitness and academic achievement in adolescents: a
      self-organizing maps approach.
AB  - The relationship among physical activity, physical fitness and academic
      achievement in adolescents has been widely studied; however, controversy
      concerning this topic persists. The methods used thus far to analyse the
      relationship between these variables have included mostly traditional lineal
      analysis according to the available literature. The aim of this study was to
      perform a visual analysis of this relationship with self-organizing maps and to
      monitor the subject's evolution during the 4 years of secondary school. Four
      hundred and forty-four students participated in the study. The physical activity
      and physical fitness of the participants were measured, and the participants'
      grade point averages were obtained from the five participant institutions. Four
      main clusters representing two primary student profiles with few differences
      between boys and girls were observed. The clustering demonstrated that students
      with higher energy expenditure and better physical fitness exhibited lower body
      mass index (BMI) and higher academic performance, whereas those adolescents with
      lower energy expenditure exhibited worse physical fitness, higher BMI and lower
      academic performance. With respect to the evolution of the students during the 4
      years, ~25% of the students originally clustered in a negative profile moved to a
      positive profile, and there was no movement in the opposite direction. 

PMID- 25953973
TI  - Making a little go a long way...
AB  - In this issue of Blood, Popat et al report the results of a clinical trial
      designed to test the safety and feasibility of a novel strategy, enforced
      fucosylation, intended to improve engraftment after donor unrelated cord blood
      (UCB) transplantation in adults. The data show that the strategy is safe, and
      that engraftment of platelets and neutrophils is faster in recipients of the
      modified cord blood (CB) unit when compared with historical controls

PMID- 25953974
TI  - Targeted drugs in concert with chemo: opposites attract.
AB  - In this issue of Blood, Brown and colleagues show an impressive additional value
      when combining a tyrosine kinase inhibitor, that is, the Bruton tyrosine kinase
      (BTK) inhibitor ibrutinib, with classic chemoimmunotherapy in patients with
      chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma

PMID- 25953975
TI  - Ph+ ALL: drawing strength from a benign past.
AB  - In this issue of Blood, Mallampati et al report on the discovery of a new
      mechanism of tyrosine kinase inhibitor (TKI) resistance, which is mediated
      through TKI-mediated priming of mesenchymal stem cells (MSCs) in the bone marrow
      (BM).

PMID- 25953977
TI  - VWF propeptide in defining VWD subtypes.
AB  - In this issue of Blood, Sanders and coworkers define the pathophysiology of types
      1, 2, and 3 von Willebrand disease (VWD) in the Willebrand in the Netherlands
      (WiN) study by using the ratios of von Willebrand factor propeptide (VWFpp) or
      factor VIII activity to VWF antigen.

PMID- 25953976
TI  - Fish provide ID(H)eas on targeting leukemia.
AB  - In this issue of Blood, Shi et al describe the role of isocitrate dehydrogenase 1
      (idh1) and idh2 in developmental hematopoiesis and demonstrate the conserved
      leukemogenic potential of human IDH1 mutations in zebrafish

PMID- 25953978
TI  - Sugar polymers exacerbate lung GVHD.
AB  - In this issue of Blood, Uryu et al demonstrate that recognition of a fungal cell
      wall component, alpha-mannan (Mn), an Mn (sugar) polymer, by the C-type lectin
      receptor Dectin-2 on host macrophages leads to a lung chemokine environment
      conducive to donor T helper (Th)17 accumulation resulting in severe pulmonary
      graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell
      transplantation (allo-HSCT). These findings shed new light on a long-standing gap
      in our understanding of the mechanistic link between infections, specifically
      fungal, and GVHD severity following allo-HSCT.

PMID- 25953979
TI  - Rising rates of acute lymphoblastic leukemia in Hispanic children: trends in
      incidence from 1992 to 2011.

PMID- 25953980
TI  - Platelet dense granule secretion defects may obscure alpha-granule secretion
      mechanisms: evidence from Munc13-4-deficient platelets.

PMID- 25953981
TI  - Give women an even chance.

PMID- 25953983
TI  - Astronomy. Telescope clash deeply rooted in Hawaii's past.

PMID- 25953984
TI  - Evolution. Deep-ocean microbe is closest living relative of complex cells.

PMID- 25953985
TI  - Biomedical research. Japan's 'NIH' starts with modest funding but high ambitions.

PMID- 25953986
TI  - Paleontology. When modern birds took flight.

PMID- 25953987
TI  - Genomics. New database links regulatory DNA to its target genes.

PMID- 25953988
TI  - Food security. Italy's olives under siege.

PMID- 25953989
TI  - King of the pills.

PMID- 25953990
TI  - Saving California's calves.

PMID- 25953991
TI  - Materials science. Understanding friction in layered materials.

PMID- 25953992
TI  - Infectious disease. More than just bugs in spit.

PMID- 25953993
TI  - Inorganic chemistry. A closer mimic of the oxygen evolution complex of
      photosystem II.

PMID- 25953994
TI  - Neurodevelopment. "RASopathic" astrocytes constrain neural plasticity.

PMID- 25953995
TI  - Conservation. Committing to ecological restoration.

PMID- 25953996
TI  - Human genetics. GTEx detects genetic effects.

PMID- 25953997
TI  - Promises and perils for the panda.

PMID- 25953999
TI  - The potential of secondary forests.

PMID- 25954000
TI  - Naming diseases: first do no harm.

PMID- 25954002
TI  - Human genomics. The human transcriptome across tissues and individuals.
AB  - Transcriptional regulation and posttranscriptional processing underlie many
      cellular and organismal phenotypes. We used RNA sequence data generated by
      Genotype-Tissue Expression (GTEx) project to investigate the patterns of
      transcriptome variation across individuals and tissues. Tissues exhibit
      characteristic transcriptional signatures that show stability in postmortem
      samples. These signatures are dominated by a relatively small number of genes
      which is most clearly seen in blood-though few are exclusive to a particular
      tissue and vary more across tissues than individuals. Genes exhibiting high
      interindividual expression variation include disease candidates associated with
      sex, ethnicity, and age. Primary transcription is the major driver of cellular
      specificity, with splicing playing mostly a complementary role; except for the
      brain, which exhibits a more divergent splicing program. Variation in splicing,
      despite its stochasticity, may play in contrast a comparatively greater role in
      defining individual phenotypes.

PMID- 25954004
TI  - Supernovae. 44Ti gamma-ray emission lines from SN1987A reveal an asymmetric
      explosion.
AB  - In core-collapse supernovae, titanium-44 ((44)Ti) is produced in the innermost
      ejecta, in the layer of material directly on top of the newly formed compact
      object. As such, it provides a direct probe of the supernova engine. Observations
      of supernova 1987A (SN1987A) have resolved the 67.87- and 78.32-kilo-electron
      volt emission lines from decay of (44)Ti produced in the supernova explosion.
      These lines are narrow and redshifted with a Doppler velocity of ~700 kilometers
      per second, direct evidence of large-scale asymmetry in the explosion. 

PMID- 25954005
TI  - Physics. Creating and probing electron whispering-gallery modes in graphene.
AB  - The design of high-finesse resonant cavities for electronic waves faces
      challenges due to short electron coherence lengths in solids. Complementing
      previous approaches to confine electronic waves by carefully positioned adatoms
      at clean metallic surfaces, we demonstrate an approach inspired by the peculiar
      acoustic phenomena in whispering galleries. Taking advantage of graphene's gate
      tunable light-like carriers, we create whispering-gallery mode (WGM) resonators
      defined by circular pn junctions, induced by a scanning tunneling probe. We can
      tune the resonator size and the carrier concentration under the probe in a back
      gated graphene device over a wide range. The WGM-type confinement and associated
      resonances are a new addition to the quantum electron-optics toolbox, paving the
      way to develop electronic lenses and resonators. 

PMID- 25954001
TI  - Human genomics. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue
      gene regulation in humans.
AB  - Understanding the functional consequences of genetic variation, and how it
      affects complex human disease and quantitative traits, remains a critical
      challenge for biomedicine. We present an analysis of RNA sequencing data from
      1641 samples across 43 tissues from 175 individuals, generated as part of the
      pilot phase of the Genotype-Tissue Expression (GTEx) project. We describe the
      landscape of gene expression across tissues, catalog thousands of tissue-specific
      and shared regulatory expression quantitative trait loci (eQTL) variants,
      describe complex network relationships, and identify signals from genome-wide
      association studies explained by eQTLs. These findings provide a systematic
      understanding of the cellular and biological consequences of human genetic
      variation and of the heterogeneity of such effects among a diverse set of human
      tissues. 

PMID- 25954006
TI  - Geophysics. Migrating tremor off southern Kyushu as evidence for slow slip of a
      shallow subduction interface.
AB  - Detection of shallow slow earthquakes offers insight into the near-trench part of
      the subduction interface, an important region in the development of great
      earthquake ruptures and tsunami generation. Ocean-bottom monitoring of offshore
      seismicity off southern Kyushu, Japan, recorded a complete episode of low
      frequency tremor, lasting for 1 month, that was associated with very-low
      frequency earthquake (VLFE) activity in the shallow plate interface. The shallow
      tremor episode exhibited two migration modes reminiscent of deep tremor down-dip
      of the seismogenic zone in some other subduction zones: a large-scale slower
      propagation mode and a rapid reversal mode. These similarities in migration
      properties and the association with VLFEs strongly suggest that both the shallow
      and deep tremor and VLFE may be triggered by the migration of episodic slow slip
      events. 

PMID- 25954007
TI  - Surface science. Adhesion and friction in mesoscopic graphite contacts.
AB  - The weak interlayer binding in two-dimensional layered materials such as graphite
      gives rise to poorly understood low-friction characteristics. Accurate
      measurements of the adhesion forces governing the overall mechanical stability
      have also remained elusive. We report on the direct mechanical measurement of
      line tension and friction forces acting in sheared mesoscale graphite structures.
      We show that the friction is fundamentally stochastic in nature and is
      attributable to the interaction between the incommensurate interface lattices. We
      also measured an adhesion energy of 0.227 +/- 0.005 joules per square meter, in
      excellent agreement with theoretical models. In addition, bistable all-mechanical
      memory cell structures and rotational bearings have been realized by exploiting
      position locking, which is provided solely by the adhesion energy. 

PMID- 25954008
TI  - Inorganic chemistry. A synthetic Mn4Ca-cluster mimicking the oxygen-evolving
      center of photosynthesis.
AB  - Photosynthetic splitting of water into oxygen by plants, algae, and cyanobacteria
      is catalyzed by the oxygen-evolving center (OEC). Synthetic mimics of the OEC,
      which is composed of an asymmetric manganese-calcium-oxygen cluster bound to
      protein groups, may promote insight into the structural and chemical determinants
      of biological water oxidation and lead to development of superior catalysts for
      artificial photosynthesis. We synthesized a Mn4Ca-cluster similar to the native
      OEC in both the metal-oxygen core and the binding protein groups. Like the native
      OEC, the synthetic cluster can undergo four redox transitions and shows two
      magnetic resonance signals assignable to redox and structural isomerism.
      Comparison with previously synthesized Mn3CaO4-cubane clusters suggests that the
      fourth Mn ion determines redox potentials and magnetic properties of the native
      OEC. 

PMID- 25954003
TI  - Human genomics. Effect of predicted protein-truncating genetic variants on the
      human transcriptome.
AB  - Accurate prediction of the functional effect of genetic variation is critical for
      clinical genome interpretation. We systematically characterized the transcriptome
      effects of protein-truncating variants, a class of variants expected to have
      profound effects on gene function, using data from the Genotype-Tissue Expression
      (GTEx) and Geuvadis projects. We quantitated tissue-specific and positional
      effects on nonsense-mediated transcript decay and present an improved predictive
      model for this decay. We directly measured the effect of variants both proximal
      and distal to splice junctions. Furthermore, we found that robustness to
      heterozygous gene inactivation is not due to dosage compensation. Our results
      illustrate the value of transcriptome data in the functional interpretation of
      genetic variants. 

PMID- 25954009
TI  - Long-term measles-induced immunomodulation increases overall childhood infectious
      disease mortality.
AB  - Immunosuppression after measles is known to predispose people to opportunistic
      infections for a period of several weeks to months. Using population-level data,
      we show that measles has a more prolonged effect on host resistance, extending
      over 2 to 3 years. We find that nonmeasles infectious disease mortality in high
      income countries is tightly coupled to measles incidence at this lag, in both the
      pre- and post-vaccine eras. We conclude that long-term immunologic sequelae of
      measles drive interannual fluctuations in nonmeasles deaths. This is consistent
      with recent experimental work that attributes the immunosuppressive effects of
      measles to depletion of B and T lymphocytes. Our data provide an explanation for
      the long-term benefits of measles vaccination in preventing all-cause infectious
      disease. By preventing measles-associated immune memory loss, vaccination
      protects polymicrobial herd immunity. 

PMID- 25954010
TI  - Chromosomes. CENP-C reshapes and stabilizes CENP-A nucleosomes at the centromere.
AB  - Inheritance of each chromosome depends upon its centromere. A histone H3 variant,
      centromere protein A (CENP-A), is essential for epigenetically marking centromere
      location. We find that CENP-A is quantitatively retained at the centromere upon
      which it is initially assembled. CENP-C binds to CENP-A nucleosomes and is a
      prime candidate to stabilize centromeric chromatin. Using purified components, we
      find that CENP-C reshapes the octameric histone core of CENP-A nucleosomes,
      rigidifies both surface and internal nucleosome structure, and modulates terminal
      DNA to match the loose wrap that is found on native CENP-A nucleosomes at
      functional human centromeres. Thus, CENP-C affects nucleosome shape and dynamics
      in a manner analogous to allosteric regulation of enzymes. CENP-C depletion leads
      to rapid removal of CENP-A from centromeres, indicating their collaboration in
      maintaining centromere identity. 

PMID- 25954011
TI  - Optogenetics. Engineering of a light-gated potassium channel.
AB  - The present palette of opsin-based optogenetic tools lacks a light-gated
      potassium (K(+)) channel desirable for silencing of excitable cells. Here, we
      describe the construction of a blue-light-induced K(+) channel 1 (BLINK1)
      engineered by fusing the plant LOV2-Jalpha photosensory module to the small viral
      K(+) channel Kcv. BLINK1 exhibits biophysical features of Kcv, including K(+)
      selectivity and high single-channel conductance but reversibly photoactivates in
      blue light. Opening of BLINK1 channels hyperpolarizes the cell to the K(+)
      equilibrium potential. Ectopic expression of BLINK1 reversibly inhibits the
      escape response in light-exposed zebrafish larvae. BLINK1 therefore provides a
      single-component optogenetic tool that can establish prolonged, physiological
      hyperpolarization of cells at low light intensities. 

PMID- 25954013
TI  - The making of a science evangelist.

PMID- 25954012
TI  - Malaria. A forward genetic screen identifies erythrocyte CD55 as essential for
      Plasmodium falciparum invasion.
AB  - Efforts to identify host determinants for malaria have been hindered by the
      absence of a nucleus in erythrocytes, which precludes genetic manipulation in the
      cell in which the parasite replicates. We used cultured red blood cells derived
      from hematopoietic stem cells to carry out a forward genetic screen for
      Plasmodium falciparum host determinants. We found that CD55 is an essential host
      factor for P. falciparum invasion. CD55-null erythrocytes were refractory to
      invasion by all isolates of P. falciparum because parasites failed to attach
      properly to the erythrocyte surface. Thus, CD55 is an attractive target for the
      development of malaria therapeutics. Hematopoietic stem cell-based forward
      genetic screens may be valuable for the identification of additional host
      determinants of malaria pathogenesis. 

PMID- 25954014
TI  - Soil science. Soil and human security in the 21st century.
AB  - Human security has and will continue to rely on Earth's diverse soil resources.
      Yet we have now exploited the planet's most productive soils. Soil erosion
      greatly exceeds rates of production in many agricultural regions. Nitrogen
      produced by fossil fuel and geological reservoirs of other fertilizers are headed
      toward possible scarcity, increased cost, and/or geopolitical conflict. Climate
      change is accelerating the microbial release of greenhouse gases from soil
      organic matter and will likely play a large role in our near-term climate future.
      In this Review, we highlight challenges facing Earth's soil resources in the
      coming century. The direct and indirect response of soils to past and future
      human activities will play a major role in human prosperity and survival. 

PMID- 25954015
TI  - A balance between TFPI and thrombin-mediated platelet activation is required for
      murine embryonic development.
AB  - Tissue factor pathway inhibitor (TFPI) is a critical anticoagulant protein
      present in endothelium and platelets. Mice lacking TFPI (Tfpi(-/-)) die in utero
      from disseminated intravascular coagulation. They are rescued by concomitant
      tissue factor (TF) deficiency, demonstrating that TFPI modulates TF function in
      vivo. Recent studies have found TFPI inhibits prothrombinase activity during the
      initiation of coagulation and limits platelet accumulation during thrombus
      formation, implicating TFPI in modulating platelet procoagulant activity. To
      examine whether altered platelet function would compensate for the lack of TFPI
      and rescue TFPI-null embryonic lethality, Tfpi(+/-) mice lacking the platelet
      thrombin receptor, protease activated receptor 4 (PAR4; Par4(-/-)), or its
      coreceptor, PAR3, were mated. PAR3 deficiency did not rescue Tfpi(-/-) embryos,
      but >40% of expected Tfpi(-/-):Par4(-/-) offspring survived to adulthood. Adult
      Tfpi(-/-):Par4(-/-) mice did not exhibit overt thrombosis. However, they had
      focal sterile inflammation with fibrin(ogen) deposition in the liver and elevated
      plasma thrombin-antithrombin complexes, indicating activation of coagulation at
      baseline. Tfpi(-/-):Par4(-/-) mice have platelet and fibrin accumulation similar
      to Par4(-/-) mice following venous electrolytic injury but were more susceptible
      than Par4(-/-) mice to TF-induced pulmonary embolism. In addition, ~30% of the
      Tfpi(-/-):Par4(-/-) mice were born with short tails. Tfpi(-/-):Par4(-/-) mice are
      the first adult mice described that lack TFPI with unaltered TF. They demonstrate
      that TFPI physiologically modulates thrombin-dependent platelet activation in a
      manner that is required for successful embryonic development and identify a role
      for TFPI in dampening intravascular procoagulant stimuli that lead to thrombin
      generation, even in the absence of thrombin-mediated platelet activation. 

PMID- 25954016
TI  - Go big or go home: impact of screening coverage on syphilis infection dynamics.
AB  - OBJECTIVES: Syphilis outbreaks in urban men who have sex with men (MSM) are an
      ongoing public health challenge in many high-income countries, despite
      intensification of efforts to screen and treat at-risk individuals. We sought to
      understand how population-level coverage of asymptomatic screening impacts the
      ability to control syphilis transmission. METHODS: We developed a risk-structured
      deterministic compartmental mathematical model of syphilis transmission in a
      population of sexually active MSM. We assumed a baseline level of treatment of
      syphilis cases due to seeking medical care in all scenarios. We evaluated the
      impact of sustained annual population-wide screening coverage ranging from 0% to
      90% on syphilis incidence over the short term (20 years) and at endemic
      equilibrium. RESULTS: The relationship between screening coverage and equilibrium
      syphilis incidence displayed an inverted U-shape relationship, with peak
      equilibrium incidence occurring with 20-30% annual screening coverage. Annual
      screening of 62% of the population was required for local elimination (incidence
      <1 case per 100 000 population). Results were qualitatively similar in the face
      of differing programmatic, behavioural and natural history assumptions, although
      the screening thresholds for local elimination differed. With 6-monthly or 3
      monthly screening, the population coverage required to achieve local elimination
      was reduced to 39% or 23%, respectively. CONCLUSIONS: Although screening has the
      potential to control syphilis outbreaks, suboptimal coverage may paradoxically
      lead to a higher equilibrium infection incidence than that observed in the
      absence of intervention. Suboptimal screening programme design should be
      considered as a possible contributor to unsuccessful syphilis control programmes
      in the context of the current epidemic.

PMID- 25954017
TI  - Sex-related differences in baseline characteristics, management and outcome in
      patients with acute coronary syndrome without ST-segment elevation.
AB  - AIM: To detect sex-related differences in baseline characteristics, management
      and outcome in patients with non-ST-segment elevation acute coronary syndrome
      (NSTE-ACS). METHODS: Data from 812 consecutive patients admitted to our
      cardiology department for NSTE-ACS between 2001 and 2004 were obtained. Early
      invasive therapy was defined as revascularization during first hospital stay. A
      seven-year follow-up for the clinical endpoint of all-cause mortality could be
      obtained in 342 women and 440 men, respectively. RESULTS: Compared with men,
      women were significantly older and more likely to suffer from renal
      insufficiency. The proportion treated with clopidogrel at admission was 43.6% for
      women and 52.7% for men, respectively (p=0.011). Significantly fewer women
      underwent an early invasive therapy compared with men (27.5% vs. 35.2%; p=0.021).
      Age and renal insufficiency were the strongest predictors for a conservative
      approach in both female and male patients. After adjustment for baseline
      characteristics there was no significant difference in treatment between women
      and men (odds ratio 0.89; 95% confidence interval 0.59-1.35; p=0.588). While in
      hospital mortality was similar between the sexes, long-term mortality was
      significantly higher in women compared with men (8.2% vs. 7.0%; p=0.549 for in
      hospital mortality and 54.8% vs. 39.3%; p<0.001 for seven-year mortality).
      However, after adjustment for baseline characteristics and treatment there was no
      significant difference in long-term mortality between women and men (hazard ratio
      1.14; 95% confidence interval 0.89-1.47; p=0.307). CONCLUSION: In these patients
      with NSTE-ACS women were less likely to undergo an early invasive therapy
      compared with men due to their higher age and the higher rate of renal
      insufficiency. After adjustment for age, comorbidities and treatment female sex
      was not associated with worse long-term outcome.

PMID- 25954018
TI  - The role of methamphetamines in psychosis-related ambulance presentations.

PMID- 25954019
TI  - Harassment, stalking, threats and attacks targeting New Zealand politicians: A
      mental health issue.
AB  - OBJECTIVE: Due to the nature of their work, politicians are at greater risk of
      stalking, harassment and attack than the general population. The small, but
      significantly elevated risk of violence to politicians is predominantly due not
      to organised terrorism or politically motivated extremists but to fixated
      individuals with untreated serious mental disorders, usually psychosis. Our
      objective was to ascertain the frequency, nature and effects of unwanted
      harassment of politicians in New Zealand and the possible role of mental illness
      in this harassment. METHODS: New Zealand Members of Parliament were surveyed,
      with an 84% response rate (n = 102). Quantitative and qualitative data were
      collected on Parliamentarians' experiences of harassment and stalking. RESULTS:
      Eighty-seven percent of politicians reported unwanted harassment ranging from
      disturbing communications to physical violence, with most experiencing harassment
      in multiple modalities and on multiple occasions. Cyberstalking and other forms
      of online harassment were common, and politicians felt they (and their families)
      had become more exposed as a result of the Internet. Half of MPs had been
      personally approached by their harassers, 48% had been directly threatened and
      15% had been attacked. Some of these incidents were serious, involving weapons
      such as guns, Molotov cocktails and blunt instruments. One in three politicians
      had been targeted at their homes. Respondents believed the majority of those
      responsible for the harassment exhibited signs of mental illness. CONCLUSION: The
      harassment of politicians in New Zealand is common and concerning. Many of those
      responsible were thought to be mentally ill by their victims. This harassment has
      significant psychosocial costs for both the victim and the perpetrator and
      represents an opportunity for mental health intervention.

PMID- 25954021
TI  - Associations of Maternal and Infant Testosterone and Cortisol Levels With
      Maternal Depressive Symptoms and Infant Socioemotional Problems.
AB  - This study examined the associations of testosterone and cortisol levels with
      maternal depressive symptoms and infant socioemotional (SE) problems that are
      influenced by infant gender. A total of 62 mothers and their very-low-birth
      weight (VLBW) infants were recruited from a neonatal intensive care unit at a
      tertiary medical center in the southeast United States. Data were collected at
      three time points (before 40 weeks' postmenstrual age [PMA] and at 3 months and 6
      months of age corrected for prematurity). Measures included infant medical record
      review, maternal interview, biochemical assays of salivary hormone levels in
      mother-VLBWinfant pairs, and standard questionnaires. Generalized estimating
      equations with separate analyses for boys and girls showed that maternal
      testosterone level was negatively associated with depressive symptoms in mothers
      of boys, whereas infant testosterone level was negatively associated with
      maternal report of infant SE problems in girls after controlling for
      characteristics of mothers and infants and number of days post birth of saliva
      collection. Not surprisingly, the SE problems were positively associated with a
      number of medical complications. Mothers with more depressive symptoms reported
      that their infants had more SE problems. Mothers with higher testosterone levels
      reported that girls, but not boys, had fewer SE problems. In summary, high levels
      of testosterone could have a protective role for maternal depressive symptoms and
      infant SE problems. Future research need to be directed toward clinical
      application of these preliminary results. 

PMID- 25954022
TI  - The Sagrada Familia splines.

PMID- 25954023
TI  - Welfare generosity and population health among Canadian provinces: a time-series
      cross-sectional analysis, 1989-2009.
AB  - BACKGROUND: Recent work in comparative social epidemiology uses an expenditures
      approach to examine the link between welfare states and population health. More
      work is needed that examines the impact of disaggregated expenditures within
      nations. This study takes advantage of provincial differences within Canada to
      examine the effects of subnational expenditures and a provincial welfare
      generosity index on population health. METHODS: Time-series cross-sectional data
      are retrieved from the Canadian Socio-Economic Information Management System II
      Tables for 1989-2009 (10 provinces and 21 years=210 cases). Expenditures are
      measured using 20 disaggregated indicators, total expenditures and a provincial
      welfare generosity index, a ombined measure of significant predictors. Health is
      measured as total, male and female age-standardised mortality rates per 1000
      deaths. Estimation techniques include the Prais-Winsten regressions with panel
      corrected SEs, a first-order autocorrelation correction model, and fixed-unit
      effects, adjusted for alternative factors. RESULTS: Analyses reveal that four
      expenditures effectively reduce mortality rates: medical care, preventive care,
      other social services and postsecondary education. The provincial welfare
      generosity index has even larger effects. For an SD increase in the provincial
      welfare generosity index, total mortality rates are expected to decline by 0.44
      SDs. Standardised effects are larger for women (beta=-0.57, z(19)=-5.70, p<0.01)
      than for men (beta=-0.38, z(19)=-5.59, p<0.01). CONCLUSIONS: Findings show that
      the expenditures approach can be effectively applied within the context of
      Canadian provinces, and that targeted spending on health, social services and
      education has salutary effects.

PMID- 25954024
TI  - Impact of changes in mode of travel to work on changes in body mass index:
      evidence from the British Household Panel Survey.
AB  - BACKGROUND: Active commuting is associated with various health benefits, but
      little is known about its causal relationship with body mass index (BMI).
      METHODS: We used cohort data from three consecutive annual waves of the British
      Household Panel Survey, a longitudinal study of nationally representative
      households, in 2004/2005 (n=15,791), 2005/2006 and 2006/2007. Participants
      selected for the analyses (n=4056) reported their usual main mode of travel to
      work at each time point. Self-reported height and weight were used to derive BMI
      at baseline and after 2 years. Multivariable linear regression analyses were used
      to assess associations between switching to and from active modes of travel (over
      1 and 2 years) and change in BMI (over 2 years) and to assess dose-response
      relationships. RESULTS: After adjustment for socioeconomic and health-related
      covariates, the first analysis (n=3269) showed that switching from private motor
      transport to active travel or public transport (n=179) was associated with a
      significant reduction in BMI compared with continued private motor vehicle use
      (n=3090; -0.32 kg/m(2), 95% CI -0.60 to -0.05). Larger adjusted effect sizes were
      associated with switching to active travel (n=109; -0.45 kg/m(2), -0.78 to 
      0.11), particularly among those who switched within the first year and those with
      the longest journeys. The second analysis (n=787) showed that switching from
      active travel or public transport to private motor transport was associated with
      a significant increase in BMI (0.34 kg/m(2), 0.05 to 0.64). CONCLUSIONS:
      Interventions to enable commuters to switch from private motor transport to more
      active modes of travel could contribute to reducing population mean BMI.

PMID- 25954025
TI  - The Effect of Viola odorata Flower Syrup on the Cough of Children With Asthma: A
      Double-Blind, Randomized Controlled Trial.
AB  - This study aimed to investigate the effect of violet syrup on cough alleviation
      in children with intermittent asthma. In a parallel, double-blind, randomized
      controlled trial, 182 children aged 2 to 12 years with intermittent asthma were
      randomly assigned 1:1 to receive violet syrup or placebo along with the common
      standard treatments in both groups (short-acting beta-agonist). Both groups were
      evaluated in terms of the duration until cough suppression was achieved. No
      significant difference was observed in basic characteristics. The duration
      lasting to yield more than 50% cough reduction and 100% cough suppression was
      significantly less in the violet syrup group compared to placebo (P = .001, P <
      .001, respectively). There was no significant difference in therapeutic effects
      between boys and girls. There was a significant inverse correlation between the
      age of children and rate of cough alleviation and suppression by violet syrup.
      This study showed that the adjuvant use of violet syrup with short-acting beta
      agonist can enhance the cough suppression in children with intermittent asthma. 

PMID- 25954026
TI  - Mutations in the planar cell polarity gene, Fuzzy, are associated with neural
      tube defects in humans.

PMID- 25954028
TI  - Systematic DNA methylation analysis of multiple cell lines reveals common and
      specific patterns within and across tissues of origin.
AB  - DNA methylation is a key functional regulatory mechanism in human genome, which
      plays critical roles in development, differentiation and many diseases. With
      rapid progress of large-scale projects (e.g. ENCODE), many DNA methylation data
      across diverse cell lines have been produced. However, common methylation
      patterns, cell lineage- and cell line-specific DNA methylation patterns across
      multiple cell lines have not yet been explored completely. Using the DNA
      methylation data across 54 human cell lines, we identified 35 276 local DNA
      methylation regions called local clusters of CpG sites (LCCSs). We constructed an
      LCCS co-methylation network and investigated the common DNA methylation patterns
      across all cell lines, which reveal two distinct groups in terms of their
      methylation level and genomic characteristics. We further detected diverse sets
      of cell lineage-specific high- and low-methylation patterns, which were depleted
      in promoter, CpG island (CGI) and repeat regions but enriched in gene body and
      non-CGI regions, especially the CGI shore regions. We discovered that the cell
      lineage-specific low-methylated LCCSs were enriched with functional
      transcriptional factor binding motif regions. Moreover, the detected cell line
      specific high- and low-methylated patterns show distinct enrichments in cell line
      specific chromatin states and functional relevance with the corresponding cell
      lines. 

PMID- 25954027
TI  - RAN translation at CGG repeats induces ubiquitin proteasome system impairment in
      models of fragile X-associated tremor ataxia syndrome.
AB  - Fragile X-associated tremor ataxia syndrome (FXTAS) is a neurodegenerative
      disorder caused by a CGG trinucleotide repeat expansion in the 5' UTR of the
      Fragile X gene, FMR1. FXTAS is thought to arise primarily from an RNA gain-of
      function toxicity mechanism. However, recent studies demonstrate that the repeat
      also elicits production of a toxic polyglycine protein, FMRpolyG, via repeat
      associated non-AUG (RAN)-initiated translation. Pathologically, FXTAS is
      characterized by ubiquitin-positive intranuclear neuronal inclusions, raising the
      possibility that failure of protein quality control pathways could contribute to
      disease pathogenesis. To test this hypothesis, we used Drosophila- and cell-based
      models of CGG-repeat-associated toxicity. In Drosophila, ubiquitin proteasome
      system (UPS) impairment led to enhancement of CGG-repeat-induced degeneration,
      whereas overexpression of the chaperone protein HSP70 suppressed this toxicity.
      In transfected mammalian cells, CGG repeat expression triggered accumulation of a
      UPS reporter in a length-dependent fashion. To delineate the contributions from
      CGG repeats as RNA from RAN translation-associated toxicity, we enhanced or
      impaired the production of FMRpolyG in these models. Driving expression of
      FMRpolyG enhanced induction of UPS impairment in cell models, while prevention of
      RAN translation attenuated UPS impairment in cells and suppressed the genetic
      interaction with UPS manipulation in Drosophila. Taken together, these findings
      suggest that CGG repeats induce UPS impairment at least in part through
      activation of RAN translation. 

PMID- 25954029
TI  - DnaJ-1 and karyopherin alpha3 suppress degeneration in a new Drosophila model of
      Spinocerebellar Ataxia Type 6.
AB  - Spinocerebellar ataxia type 6 (SCA6) belongs to the family of CAG/polyglutamine
      (polyQ)-dependent neurodegenerative disorders. SCA6 is caused by abnormal
      expansion in a CAG trinucleotide repeat within exon 47 of CACNA1A, a bicistronic
      gene that encodes alpha1A, a P/Q-type calcium channel subunit and a C-terminal
      protein, termed alpha1ACT. Expansion of the CAG/polyQ region of CACNA1A occurs
      within alpha1ACT and leads to ataxia. There are few animal models of SCA6. Here,
      we describe the generation and characterization of the first Drosophila
      melanogaster models of SCA6, which express the entire human alpha1ACT protein
      with a normal or expanded polyQ. The polyQ-expanded version of alpha1ACT
      recapitulates the progressively degenerative nature of SCA6 when expressed in
      various fly tissues and the presence of densely staining aggregates. Additional
      studies identify the co-chaperone DnaJ-1 as a potential therapeutic target for
      SCA6. Expression of DnaJ-1 potently suppresses alpha1ACT-dependent degeneration
      and lethality, concomitant with decreased aggregation and reduced nuclear
      localization of the pathogenic protein. Mutating the nuclear importer karyopherin
      alpha3 also leads to reduced toxicity from pathogenic alpha1ACT. Little is known
      about the steps leading to degeneration in SCA6 and the means to protect neurons
      in this disease are lacking. Invertebrate animal models of SCA6 can expand our
      understanding of molecular sequelae related to degeneration in this disorder and
      lead to the rapid identification of cellular components that can be targeted to
      treat it. 

PMID- 25954030
TI  - Mutation of the nuclear lamin gene LMNB2 in progressive myoclonus epilepsy with
      early ataxia.
AB  - We studied a consanguineous Palestinian Arab family segregating an autosomal
      recessive progressive myoclonus epilepsy (PME) with early ataxia. PME is a rare,
      often fatal syndrome, initially responsive to antiepileptic drugs which over time
      becomes refractory and can be associated with cognitive decline. Linkage analysis
      was performed and the disease locus narrowed to chromosome 19p13.3. Fourteen
      candidate genes were screened by conventional Sanger sequencing and in one,
      LMNB2, a novel homozygous missense mutation was identified that segregated with
      the PME in the family. Whole exome sequencing excluded other likely pathogenic
      coding variants in the linked interval. The p.His157Tyr mutation is located in an
      evolutionarily highly conserved region of the alpha-helical rod of the lamin B2
      protein. In vitro assembly analysis of mutant lamin B2 protein revealed a
      distinct defect in the assembly of the highly ordered fibrous arrays typically
      formed by wild-type lamin B2. Our data suggests that disruption of the
      organisation of the nuclear lamina in neurons, perhaps through abnormal neuronal
      migration, causes the epilepsy and early ataxia syndrome and extends the
      aetiology of PMEs to include dysfunction in nuclear lamin proteins. 

PMID- 25954031
TI  - Spatiotemporal dynamics of the postnatal developing primate brain transcriptome.
AB  - Developmental changes in the temporal and spatial regulation of gene expression
      drive the emergence of normal mature brain function, while disruptions in these
      processes underlie many neurodevelopmental abnormalities. To solidify our
      foundational knowledge of such changes in a primate brain with an extended period
      of postnatal maturation like in human, we investigated the whole-genome
      transcriptional profiles of rhesus monkey brains from birth to adulthood. We
      found that gene expression dynamics are largest from birth through infancy, after
      which gene expression profiles transition to a relatively stable state by young
      adulthood. Biological pathway enrichment analysis revealed that genes more highly
      expressed at birth are associated with cell adhesion and neuron differentiation,
      while genes more highly expressed in juveniles and adults are associated with
      cell death. Neocortex showed significantly greater differential expression over
      time than subcortical structures, and this trend likely reflects the protracted
      postnatal development of the cortex. Using network analysis, we identified 27 co
      expression modules containing genes with highly correlated expression patterns
      that are associated with specific brain regions, ages or both. In particular, one
      module with high expression in neonatal cortex and striatum that decreases during
      infancy and juvenile development was significantly enriched for autism spectrum
      disorder (ASD)-related genes. This network was enriched for genes associated with
      axon guidance and interneuron differentiation, consistent with a disruption in
      the formation of functional cortical circuitry in ASD. 

PMID- 25954032
TI  - Gpr126/Adgrg6 deletion in cartilage models idiopathic scoliosis and pectus
      excavatum in mice.
AB  - Adolescent idiopathic scoliosis (AIS) and pectus excavatum (PE) are common
      pediatric musculoskeletal disorders. Little is known about the tissue of origin
      for either condition, or about their genetic bases. Common variants near
      GPR126/ADGRG6 (encoding the adhesion G protein-coupled receptor 126/adhesion G
      protein-coupled receptor G6, hereafter referred to as GPR126) were recently shown
      to be associated with AIS in humans. Here, we provide genetic evidence that loss
      of Gpr126 in osteochondroprogenitor cells alters cartilage biology and spinal
      column development. Microtomographic and x-ray studies revealed several hallmarks
      of AIS, including postnatal onset of scoliosis without malformations of vertebral
      units. The mutants also displayed a dorsal-ward deflection of the sternum akin to
      human PE. At the cellular level, these defects were accompanied by failure of
      midline fusion within the developing annulus fibrosis of the intervertebral discs
      and increased apoptosis of chondrocytes in the ribs and vertebrae. Molecularly,
      we found that loss of Gpr126 upregulated the expression of Gal3st4, a gene
      implicated in human PE, encoding Galactose-3-O-sulfotransferase 4. Together,
      these data uncover Gpr126 as a genetic cause for the pathogenesis of AIS and PE
      in a mouse model. 

PMID- 25954033
TI  - DLX4 is associated with orofacial clefting and abnormal jaw development.
AB  - Cleft lip and/or palate (CL/P) are common structural birth defects in humans. We
      used exome sequencing to study a patient with bilateral CL/P and identified a
      single nucleotide deletion in the patient and her similarly affected son
      c.546_546delG, predicting p.Gln183Argfs*57 in the Distal-less 4 (DLX4) gene. The
      sequence variant was absent from databases, predicted to be deleterious and was
      verified by Sanger sequencing. In mammals, there are three Dlx homeobox clusters
      with closely located gene pairs (Dlx1/Dlx2, Dlx3/Dlx4, Dlx5/Dlx6). In situ
      hybridization showed that Dlx4 was expressed in the mesenchyme of the murine
      palatal shelves at E12.5, prior to palate closure. Wild-type human DLX4, but not
      mutant DLX4_c.546delG, could activate two murine Dlx conserved regulatory
      elements, implying that the mutation caused haploinsufficiency. We showed that
      reduced DLX4 expression after short interfering RNA treatment in a human cell
      line resulted in significant up-regulation of DLX3, DLX5 and DLX6, with reduced
      expression of DLX2 and significant up-regulation of BMP4, although the increased
      BMP4 expression was demonstrated only in HeLa cells. We used antisense morpholino
      oligonucleotides to target the orthologous Danio rerio gene, dlx4b, and found
      reduced cranial size and abnormal cartilaginous elements. We sequenced DLX4 in
      155 patients with non-syndromic CL/P and CP, but observed no sequence variants.
      From the published literature, Dlx1/Dlx2 double homozygous null mice and Dlx5
      homozygous null mice both have clefts of the secondary palate. This first finding
      of a DLX4 mutation in a family with CL/P establishes DLX4 as a potential cause of
      human clefts.

PMID- 25954034
TI  - The pro-domains of neurotrophins, including BDNF, are linked to Alzheimer's
      disease through a toxic synergy with Abeta.
AB  - Brain-derived neurotrophic factor (BDNF) has a crucial role in learning and
      memory by promoting neuronal survival and modulating synaptic connectivity. BDNF
      levels are lower in the brains of individuals with Alzheimer's disease (AD),
      suggesting a pathogenic involvement. The Drosophila orthologue of BDNF is the
      highly conserved Neurotrophin 1 (DNT1). BDNF and DNT1 have the same overall
      protein structure and can be cleaved, resulting in the conversion of a full
      length polypeptide into separate pro- and mature-domains. While the BDNF mature
      domain is neuroprotective, the role of the pro-domain is less clear. In flies and
      mammalian cells, we have identified a synergistic toxic interaction between the
      amyloid-beta peptide (Abeta1-42) and the pro-domains of both DNT1 and BDNF.
      Specifically, we show that DNT1 pro-domain acquires a neurotoxic activity in the
      presence of Abeta1-42. In contrast, DNT1 mature-domain is protective against
      Abeta1-42 toxicity. Likewise, in SH-SY5Y cell culture, BDNF pro-domain is toxic
      only in the presence of Abeta1-42. Western blots indicate that this synergistic
      interaction likely results from the Abeta1-42-induced upregulation of the BDNF
      pro-domain receptor p75(NTR). The clinical relevance of these findings is
      underlined by a greater than thirty fold increase in the ratio of BDNF pro- to
      mature-domains in the brains of individuals with AD. This unbalanced BDNF
      pro:mature-domain ratio in patients represents a possible biomarker of AD and may
      offer a target for therapeutic intervention. 

PMID- 25954035
TI  - Effects of over-the-counter analgesic use on reproductive hormones and ovulation
      in healthy, premenopausal women.
AB  - STUDY QUESTION: Does use of commonly used over-the-counter (OTC) pain medication
      affect reproductive hormones and ovulatory function in premenopausal women?
      SUMMARY ANSWER: Few associations were found between analgesic medication use and
      reproductive hormones, but use during the follicular phase was associated with
      decreased odds of sporadic anovulation after adjusting for potential confounders.
      WHAT IS KNOWN ALREADY: Analgesic medications are the most commonly used OTC drugs
      among women, but their potential effects on reproductive function are unclear.
      STUDY DESIGN, SIZE, DURATION: The BioCycle Study was a prospective, observational
      cohort study (2005-2007) which followed 259 women for one (n = 9) or two (n =
      250) menstrual cycles. PARTICIPANTS, SETTING, METHODS: Two hundred and fifty-nine
      healthy, premenopausal women not using hormonal contraception and living in
      western New York state. Study visits took place at the University at Buffalo.
      MAIN RESULTS AND THE ROLE OF CHANCE: During study participation, 68% (n = 175) of
      women indicated OTC analgesic use. Among users, 45% used ibuprofen, 33%
      acetaminophen, 10% aspirin and 10% naproxen. Analgesic use during the follicular
      phase was associated with decreased odds of sporadic anovulation after adjusting
      for age, race, body mass index, perceived stress level and alcohol consumption
      (OR 0.36 [0.17, 0.75]). Results remained unchanged after controlling for
      potential confounding by indication by adjusting for 'healthy' cycle indicators
      such as amount of blood loss and menstrual pain during the preceding
      menstruation. Moreover, luteal progesterone was higher (% difference = 14.0, -1.6
      32.1, P = 0.08 adjusted) in cycles with follicular phase analgesic use, but no
      associations were observed with estradiol, LH or FSH. LIMITATIONS, REASONS FOR
      CAUTION: Self-report daily diaries are not validated measures of medication
      usage, which could lead to some classification error of medication use. We were
      also limited in our evaluation of aspirin and naproxen which were used by few
      women. WIDER IMPLICATIONS OF THE FINDINGS: The observed associations between
      follicular phase analgesic use and higher progesterone and a lower probability of
      sporadic anovulation indicate that OTC pain medication use is likely not harmful
      to reproduction function, and certain medications possibly improve ovulatory
      function. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the
      Intramural Research Program of the Eunice Kennedy Shriver National Institute of
      Child Health and Human Development, National Institutes of Health (contract #
      HHSN275200403394C). The authors have no conflicts of interest to disclose.

PMID- 25954036
TI  - Disclosure strategies, social support, and quality of life in infertile women.
AB  - STUDY QUESTION: Do the strategies women use to disclose information about their
      infertility to social network members impact the quality of the support they
      receive and their quality of life? SUMMARY ANSWER: The data showed that women who
      disclosed infertility-related information in direct ways, rather than in indirect
      ways (e.g. by incremental disclosures or through third parties), to social
      network members perceived higher quality support and reported greater quality of
      life related to their infertility experience. WHAT IS KNOWN ALREADY: Social
      support has been shown to buffer stress associated with various health issues
      including infertility. The way people disclose information about stressors has
      been associated with the quality of the support they receive. Disclosing
      information in a way that most effectively elicits support is beneficial because
      women with infertility who have lower levels of stress are more likely to seek
      and remain in treatment. STUDY DESIGN, SIZE, DURATION: This cross-sectional study
      of 301 infertile women was conducted in the USA. PARTICIPANTS/MATERIALS, SETTING,
      METHODS: To determine the variation in length of infertility and treatment
      decisions, we conducted an online survey of 301 American women coping with
      infertility. We investigated the strategies women used to disclose infertility
      related information with social network members, their perceptions of support
      from friends and family, and their quality of life both in general (overall
      quality of life) and related to the experience of infertility (fertility quality
      of life). MAIN RESULTS AND THE ROLE OF CHANCE: Direct disclosure of experiences
      related to infertility was positively and significantly associated with the
      perceived quality of social support received (P < 0.01). Strategies of disclosure
      that use entrapment or indirect media were negatively associated with fertility
      quality of life (P < 0.001). Directly (P < 0.01) and incremental disclosures (P <
      0.01) were positively associated with overall quality of life, while the use of
      humor was negatively associated with overall quality of life (P < 0.01).
      Perceived support quality also mediated the influence of direct disclosures on
      women's fertility quality of life (95% CI: 0.18, 1.05) and overall quality of
      life (95% CI: 0.10, 0.30). This effect is particularly noteworthy for the model
      predicting fertility quality of life, which exhibited a non-significant main
      effect with direct disclosures. The non-significant main effect combined with the
      significant indirect effect suggests that perceived support quality fully
      mediates the association between direct disclosures and fertility quality of
      life. LIMITATIONS, REASONS FOR CAUTION: The cross-sectional nature of our
      convenient sample did not allow us to test cause and effect. It is equally
      plausible that women who perceive support are more likely to disclose.
      Longitudinal data are necessary to test the cyclic nature of these variables and
      confirm directionality. WIDER IMPLICATIONS OF THE FINDINGS: When women make the
      decision to reveal information about their infertility, direct disclosure (i.e.
      face-to-face, clearly, verbally and with the opportunity for an immediate
      response) was the only strategy that significantly corresponded with perceived
      support quality and was one of only two strategies that were positively
      associated with quality of life. To the extent that social support reduces
      stress, and lower stress increases the chance that people seek and stay in
      treatment, infertility clinics and therapists can use this information as a low
      cost strategy for supporting infertile women. Scholars and practitioners can also
      instruct women coping with infertility about how to most effectively engage in
      seeking effective support. STUDY FUNDING/COMPETING INTERESTS: No external funding
      was either sought or obtained for this study and no competing interests are
      declared.

PMID- 25954037
TI  - Uterine artery embolization for uterine arteriovenous malformation in five women
      desiring fertility: pregnancy outcomes.
AB  - Uterine arteriovenous malformations (AVM) are rare and can be classified as
      either congenital or acquired. Acquired AVMs may result from trauma, uterine
      instrumentation, infection or gestational trophoblastic disease. The majority of
      acquired AVMs are encountered in women of reproductive age with a history of at
      least one pregnancy. Traditional therapies of AVMs include medical management of
      symptomatic bleeding, blood transfusions, uterine artery embolization (UAE) or
      hysterectomy. In this retrospective case series, we report our experience with
      AVM and UAE in five symptomatic women of reproductive age who wished to preserve
      fertility. Patients were 18-32 years old, and had 1-3 previous pregnancies prior
      to initial presentation. All patients were followed until their deliveries. All
      five patients delivered live births. Three of the five patients required two
      embolization procedures and one of these women required a subsequent
      hysterectomy. Two deliveries were at term and had normal weight babies and normal
      placenta. One woman had cerclage placed and developed chorioamnionitis at 34
      weeks but had a normal placenta. Two pregnancies were induced <37 weeks for pre
      eclampsia/b intrauterine growth restriction +/- abnormal umbilical artery
      dopplers. The low birthweight were both <2000 g. Both placentas showed
      accelerated maturity and infarcts. All estimated blood losses were recorded as
      <500 cc. In conclusion, UAE may not be as effective at managing AVM as previously
      thought and should be questioned as an initial therapy in symptomatic women of
      reproductive age desiring fertility preservation. 

PMID- 25954038
TI  - Enough! Stop the arguments and get on with the science of natural killer cell
      testing.
AB  - Natural killer cell testing is currently practised widely, and there are studies
      indicating potential benefit in terms of targeting women with repeated
      reproductive failure for immune therapy. This may be a better approach than
      empirical immune therapy without any investigation. More and better studies are
      needed before such an approach can be fully endorsed. There is still uncertainty
      over the precise pathophysiological basis for all immune investigation and
      therapy, but this should not be a barrier for clinical observation and empirical
      care. On the contrary, clinicians and researchers should work more closely
      together to provide the best care for our patients. 

PMID- 25954040
TI  - Insight into post-transcriptional gene regulation: stress-responsive microRNAs
      and their role in the environmental stress survival of tolerant animals.
AB  - Living animals are constantly faced with various environmental stresses that
      challenge normal life, including: oxygen limitation, very low or high
      temperature, as well as restriction of water and food. It has been well
      established that in response to these stresses, tolerant organisms regularly
      respond with a distinct suite of cellular modifications that involve
      transcriptional, translational and post-translational modification. In recent
      years, a new mechanism of rapid and reversible transcriptome regulation, via the
      action of non-coding RNA molecules, has emerged into post-transcriptional
      regulation and has since been shown to be part of the survival response. However,
      these RNA-based mechanisms by which tolerant organisms respond to stressed
      conditions are not well understood. Recent studies have begun to show that non
      coding RNAs control gene expression and translation of mRNA to protein, and can
      also have regulatory influence over major cellular processes. For example, select
      microRNAs have been shown to have regulatory influence over the cell cycle,
      apoptosis, signal transduction, muscle atrophy and fatty acid metabolism during
      periods of environmental stress. As we are on the verge of dissecting the roles
      of non-coding RNA in environmental stress adaptation, this Commentary summarizes
      the hallmark alterations in microRNA expression that facilitate stress survival. 

PMID- 25954039
TI  - First do no harm: uterine natural killer (NK) cells in assisted reproduction.
AB  - Natural killer (NK) cells are a type of lymphocyte circulating in peripheral
      blood named because of their effector functions in killing target cells. Immune
      cells that share similar phenotypic characteristics but are poor killers populate
      the uterine lining at implantation and during early pregnancy when the placenta
      is established. The functions of these uterine NK (uNK) cells are essentially
      unknown but available data point to a role in regulating placentation in concert
      with other elements of the decidua and invading trophoblast cells. Despite the
      lack of scientific rationale and advice from clinical governing bodies, such as
      the Human Fertilisation and Embryology Authority, an increasing range of tests
      and therapies are still offered to women undergoing IVF or attending recurrent
      miscarriage clinics based on the myth that uterine NK cells need suppressing to
      prevent damage to the embryo. New treatments can be introduced at whim with
      subsequent demands for expensive trials to prove/disprove their efficacy. The
      evidence that targeting uNK or peripheral blood NK cells assists women with
      recurrent pregnancy failure is lacking. Healthcare professionals and patients
      should very carefully evaluate the practice of immunomodulation to enhance
      pregnancy outcome. A discussion on how to move towards stricter regulation of
      immunotherapy in non-hospital settings is now needed because it is clear that the
      potential risks and costs of these therapies outweigh any benefits. 

PMID- 25954041
TI  - Behavioral and mechanical determinants of collective subsurface nest excavation.
AB  - Collective construction of topologically complex structures is one of the
      triumphs of social behavior. For example, many ant species construct underground
      nests composed of networks of tunnels and chambers. Excavation by these
      'superorganisms' depends on the biomechanics of substrate manipulation, the
      interaction of individuals, and media stability and cohesiveness. To discover
      principles of robust social excavation, we used X-ray computed tomography to
      monitor the growth in three dimensions of nests built by groups of fire ants
      (Solenopsis invicta) in laboratory substrates composed of silica particles,
      manipulating two substrate properties: particle size and gravimetric moisture
      content. Ants were capable of nest construction in all substrates tested other
      than completely dry or fully saturated; for a given particle size, nest volume
      was relatively insensitive to moisture content. Tunnels were deepest at
      intermediate moisture content and the maximum tunnel depth correlated with
      measured yield force on small rod-shaped intruders (a proxy for cohesive
      strength). This implies that increased cohesive strength allowed creation of
      tunnels that were resistant to perturbation but did not decrease individual
      excavation ability. Ants used two distinct behaviors to create pellets composed
      of wetted particles, depending on substrate composition. However, despite the
      ability to create larger stable pellets in more cohesive substrates, pellet sizes
      were similar across all conditions. We posit that this pellet size balances the
      individual's load-carrying ability with the need to carry this pellet through
      confined crowded tunnels. We conclude that effective excavation of similarly
      shaped nests can occur in a diversity of substrates through sophisticated digging
      behaviors by individuals which accommodate both differing substrate properties
      and the need to work within the collective.

PMID- 25954042
TI  - Gait switches in deep-diving beaked whales: biomechanical strategies for long
      duration dives.
AB  - Diving animals modulate their swimming gaits to promote locomotor efficiency and
      so enable longer, more productive dives. Beaked whales perform extremely long and
      deep foraging dives that probably exceed aerobic capacities for some species.
      Here, we use biomechanical data from suction-cup tags attached to three species
      of beaked whales (Mesoplodon densirostris, N=10; Ziphius cavirostris, N=9; and
      Hyperoodon ampullatus, N=2) to characterize their swimming gaits. In addition to
      continuous stroking and stroke-and-glide gaits described for other diving
      mammals, all whales produced occasional fluke-strokes with distinctly larger
      dorso-ventral acceleration, which we termed 'type-B' strokes. These high-power
      strokes occurred almost exclusively during deep dive ascents as part of a novel
      mixed gait. To quantify body rotations and specific acceleration generated during
      strokes we adapted a kinematic method combining data from two sensors in the tag.
      Body rotations estimated with high-rate magnetometer data were subtracted from
      accelerometer data to estimate the resulting surge and heave accelerations. Using
      this method, we show that stroke duration, rotation angle and acceleration were
      bi-modal for these species, with B-strokes having 76% of the duration, 52% larger
      body rotation and four times more surge than normal strokes. The additional
      acceleration of B-strokes did not lead to faster ascents, but rather enabled
      brief glides, which may improve the overall efficiency of this gait. Their
      occurrence towards the end of long dives leads us to propose that B-strokes may
      recruit fast-twitch fibres that comprise ~80% of swimming muscles in Blainville's
      beaked whales, thus prolonging foraging time at depth.

PMID- 25954043
TI  - Proteomic analysis of cardiac response to thermal acclimation in the eurythermal
      goby fish Gillichthys mirabilis.
AB  - Cardiac function is thought to play a central role in determining thermal optima
      and tolerance limits in teleost fishes. Investigating proteomic responses to
      temperature in cardiac tissues may provide insights into mechanisms supporting
      the thermal plasticity of cardiac function. Here, we utilized a global proteomic
      analysis to investigate changes in cardiac protein abundance in response to
      temperature acclimation (transfer from 13 degrees C to 9, 19 and 26 degrees C) in
      a eurythermal goby, Gillichthys mirabilis. Proteomic data revealed 122
      differentially expressed proteins across acclimation groups, 37 of which were
      identified using tandem mass-spectrometry. These 37 proteins are involved in
      energy metabolism, mitochondrial regulation, iron homeostasis, cytoprotection
      against hypoxia, and cytoskeletal organization. Compared with the 9 and 26
      degrees C groups, proteins involved in energy metabolism increased in 19 degrees
      C-acclimated fish, indicating an overall increase in the capacity for ATP
      production. Creatine kinase abundance increased in 9 degrees C-acclimated fish,
      suggesting an important role for the phosphocreatine energy shuttle in cold
      acclimated hearts. Both 9 and 26 degrees C fish also increased abundance of
      hexosaminidase, a protein directly involved in post-hypoxia stress cytoprotection
      of cardiac tissues. Cytoskeletal restructuring appears to occur in all
      acclimation groups; however, the most prominent effect was detected in 26 degrees
      C-acclimated fish, which exhibited significantly increased actin levels. Overall,
      proteomic analysis of cardiac tissue suggests that the capacity to adjust ATP
      generating processes is crucial to the thermal plasticity of cardiac function.
      Furthermore, G. mirabilis may optimize cellular functions at temperatures near 19
      degrees C, which lies within the species' preferred temperature range.

PMID- 25954044
TI  - Size dependence in non-sperm ejaculate production is reflected in daily energy
      expenditure and resting metabolic rate.
AB  - The non-sperm components of an ejaculate, such as copulatory plugs, can be
      essential to male reproductive success. But the costs of these ejaculate
      components are often considered trivial. In polyandrous species, males are
      predicted to increase energy allocation to the production of non-sperm
      components, but this allocation is often condition dependent and the energetic
      costs of their production have never been quantified. Red-sided garter snakes
      (Thamnophis sirtalis parietalis) are an excellent model with which to quantify
      the energetic costs of non-sperm components of the ejaculate as they exhibit a
      dissociated reproductive pattern in which sperm production is temporally disjunct
      from copulatory plug production, mating and plug deposition. We estimated the
      daily energy expenditure and resting metabolic rate of males after courtship and
      mating, and used bomb calorimetry to estimate the energy content of copulatory
      plugs. We found that both daily energy expenditure and resting metabolic rate
      were significantly higher in small mating males than in courting males, and a
      single copulatory plug without sperm constitutes 5-18% of daily energy
      expenditure. To our knowledge, this is the first study to quantify the energetic
      expense of size-dependent ejaculate strategies in any species. 

PMID- 25954046
TI  - Diversion of carbon flux from gibberellin to steviol biosynthesis by over
      expressing SrKA13H induced dwarfism and abnormality in pollen germination and
      seed set behaviour of transgenic Arabidopsis.
AB  - This paper documents the engineering of Arabidopsis thaliana for the ectopic over
      expression of SrKA13H (ent-kaurenoic acid-13 hydroxylase) cDNA from Stevia
      rebaudiana. HPLC analysis revealed the significant accumulation of steviol (1-3
      MUg g(-1) DW) in two independent transgenic Arabidopsis lines over-expressing
      SrKA13H compared with the control. Independent of the steviol concentrations
      detected, both transgenic lines showed similar reductions in endogenous bioactive
      gibberellins (GA1 and GA4). They possessed phenotypic similarity to gibberellin
      deficient mutants. The reduction in endogenous gibberellin content was found to
      be responsible for dwarfism in the transgenics. The exogenous application of GA3
      could rescue the transgenics from dwarfism. The hypocotyl, rosette area, and stem
      length were all considerably reduced in the transgenics. A noteworthy decrease in
      pollen viability was noticed and, similarly, a retardation of 60-80% in pollen
      germination rate was observed. The exogenous application of steviol (0.2, 0.5,
      and 1.0 MUg ml(-1)) did not influence pollen germination efficiency. This has
      suggested that in planta formation of steviol was not responsible for the
      observed changes in transgenic Arabidopsis. Further, the seed yield of the
      transgenics was reduced by 24-48%. Hence, this study reports for the first time
      that over-expression of SrKA13H cDNA in Arabidopsis has diverted the gibberellin
      biosynthetic route towards steviol biosynthesis. The Arabidopsis transgenics
      showed a significant reduction in endogenous gibberellins that might be
      responsible for the dwarfism, and the abnormal behaviour of pollen germination
      and seed set. 

PMID- 25954045
TI  - Growth and physiological responses of isohydric and anisohydric poplars to
      drought.
AB  - Understanding how different plants prioritize carbon gain and drought
      vulnerability under a variable water supply is important for predicting which
      trees will maximize woody biomass production under different environmental
      conditions. Here, Populus balsamifera (BS, isohydric genotype), P. simonii (SI,
      previously uncharacterized stomatal behaviour), and their cross, P. balsamifera x
      simonii (BSxSI, anisohydric genotype) were studied to assess the physiological
      basis for biomass accumulation and water-use efficiency across a range of water
      availabilities. Under ample water, whole plant stomatal conductance (gs),
      transpiration (E), and growth rates were higher in anisohydric genotypes (SI and
      BSxSI) than in isohydric poplars (BS). Under drought, all genotypes regulated the
      leaf to stem water potential gradient via changes in gs, synchronizing leaf
      hydraulic conductance (Kleaf) and E: isohydric plants reduced Kleaf, gs, and E,
      whereas anisohydric genotypes maintained high Kleaf and E, which reduced both
      leaf and stem water potentials. Nevertheless, SI poplars reduced their plant
      hydraulic conductance (Kplant) during water stress and, unlike, BSxSI plants,
      recovered rapidly from drought. Low gs of the isohydric BS under drought reduced
      CO2 assimilation rates and biomass potential under moderate water stress. While
      anisohydric genotypes had the fastest growth under ample water and higher
      photosynthetic rates under increasing water stress, isohydric poplars had higher
      water-use efficiency. Overall, the results indicate three strategies for how
      closely related biomass species deal with water stress: survival-isohydric (BS),
      sensitive-anisohydric (BSxSI), and resilience-anisohydric (SI). Implications for
      woody biomass growth, water-use efficiency, and survival under variable
      environmental conditions are discussed. 

PMID- 25954047
TI  - Effect of carbohydrates and night temperature on night respiration in rice.
AB  - Global warming causes night temperature (NT) to increase faster than day
      temperature in the tropics. According to crop growth models, respiration incurs a
      loss of 40-60% of photosynthate. The thermal sensitivity of night respiration
      (R(n)) will thus reduce biomass. Instantaneous and acclimated effects of NT on
      R(n) of leaves and seedlings of two rice cultivars having a variable level of
      carbohydrates, induced by exposure to different light intensity on the previous
      day, were investigated. Experiments were conducted in a greenhouse and growth
      chambers, with R(n) measured on the youngest fully expanded leaves or whole
      seedlings. Dry weight-based R(n) was 2.6-fold greater for seedlings than for
      leaves. Leaf R(n) was linearly related to starch (positive intercept) and soluble
      sugar concentration (zero intercept). Increased NT caused higher R(n) at a given
      carbohydrate concentration. The change of R(n) at NT increasing from 21  degrees
      C to 31  degrees C was 2.4-fold for the instantaneous response but 1.2- to 1.7
      fold after acclimation. The maintenance component of R(n) (R(m)'), estimated by
      assimilate starvation, averaged 28% in seedlings and 34% in leaves, with no
      significant thermal effect on this ratio. The acclimated effect of increased NT
      on R(m)' across experiments was 1.5-fold for a 10  degrees C increase in NT. No
      cultivar differences were observed in R(n) or R(m)' responses. The results
      suggest that the commonly used Q10=2 rule overestimates thermal response of
      respiration, and R(n) largely depends on assimilate resources.

PMID- 25954048
TI  - Nitric oxide (NO) and phytohormones crosstalk during early plant development.
AB  - During the past two decades, nitric oxide (NO) has evolved from a mere gaseous
      free radical to become a new messenger in plant biology with an important role in
      a plethora of physiological processes. This molecule is involved in the
      regulation of plant growth and development, pathogen defence and abiotic stress
      responses, and in most cases this is achieved through its interaction with
      phytohormones. Understanding the role of plant growth regulators is essential to
      elucidate how plants activate the appropriate set of responses to a particular
      developmental stage or a particular stress. The first task to achieve this goal
      is the identification of molecular targets, especially those involved in the
      regulation of the crosstalk. The nature of NO targets in these growth and
      development processes and stress responses remains poorly described. Currently,
      the molecular mechanisms underlying the effects of NO in these processes and
      their interaction with other plant hormones are beginning to unravel. In this
      review, we made a compilation of the described interactions between NO and
      phytohormones during early plant developmental processes (i.e. seed dormancy and
      germination, hypocotyl elongation and root development). 

PMID- 25954049
TI  - High Oral Human Papillomavirus Type 16 Load Predicts Long-term Persistence in
      Individuals With or at Risk for HIV Infection.
AB  - The association between oral human papillomavirus 16 (HPV16) DNA load and
      infection clearance was evaluated among 88 individuals with oral HPV16 infection
      who were identified within a prospective cohort of 1470 HIV-infected and
      uninfected individuals. Oral rinse specimens were collected semiannually for up
      to 5 years. The oral HPV16 load at the time of the first positive test result was
      significantly associated with the time to clearance of infection (continuous P
      trends <.01). Notably, clearance rates by 24 months were 41% and 94% in the
      highest and lowest HPV16 load tertiles (P = .03), respectively. High oral HPV16
      load warrants consideration as a biomarker for infection persistence, the
      presumed precursor of HPV16-associated oropharyngeal cancer. 

PMID- 25954051
TI  - Accessing photo-based morphological control in phase-separated, cross-linked
      networks through delayed gelation.
AB  - This work presents an approach to extend the period for phase separation,
      independent of temperature, in ambient phase-separating photopolymerizations
      based on the copolymerization of structurally similar mono- and di-vinyl
      monomers. Copolymer resins composed of triethylene glycol dimethacrylate (TEGDMA)
      and ethylene glycol methyl ether methacrylate (EGMEMA) were modified with a
      thermoplastic prepolymer, poly(butyl methacrylate). With increasing EGMEMA
      modification into the bulk TEGDMA resin, there is a decrease in the initial
      reaction rate, which increases the time for development of compositionally
      different phases prior to network gelation. The period between phase separation
      and gelation was probed through optical and rheological measurements, and it was
      extended from 22 s in a TEGDMA resin to 69 s in a TEGDMA:EGMEMA copolymer,
      allowing these materials to be processed under a wide range of UV-irradiation
      intensities (300 uW cm-2 - 100 mW cm-2), which provided an additional degree of
      control over the resulting phase separated domain size and morphology.

PMID- 25954050
TI  - Inactivation of ANGPTL3 reduces hepatic VLDL-triglyceride secretion.
AB  - Humans and mice lacking angiopoietin-like protein 3 (ANGPTL3) have pan
      hypolipidemia. ANGPTL3 inhibits two intravascular lipases, LPL and endothelial
      lipase, and the low plasma TG and HDL-cholesterol levels in ANGPTL3 deficiency
      reflect increased activity of these enzymes. The mechanism responsible for the
      low LDL-cholesterol levels associated with ANGPTL3 deficiency is not known. Here
      we used an anti-ANGPTL3 monoclonal antibody (REGN1500) to inactivate ANGPTL3 in
      mice with genetic deficiencies in key proteins involved in clearance of ApoB
      containing lipoproteins. REGN1500 treatment consistently reduced plasma
      cholesterol levels in mice in which Apoe, Ldlr, Lrp1, and Sdc1 were inactivated
      singly or in combination, but did not alter clearance of rabbit (125)I-betaVLDL
      or mouse (125)I-LDL. Despite a 61% reduction in VLDL-TG production, VLDL-ApoB-100
      production was unchanged in REGN1500-treated animals. Hepatic TG content, fatty
      acid synthesis, and fatty acid oxidation were similar in REGN1500 and control
      antibody-treated animals. Taken together, our findings indicate that inactivation
      of ANGPTL3 does not affect the number of ApoB-containing lipoproteins secreted by
      the liver but alters the particles that are made such that they are cleared more
      rapidly from the circulation via a noncanonical pathway(s). The increased
      clearance of lipolytic remnants results in decreased production of LDL in ANGPTL3
      deficient animals. 

PMID- 25954052
TI  - Long-term changes to the frequency of occurrence of British moths are consistent
      with opposing and synergistic effects of climate and land-use changes.
AB  - Species' distributions are likely to be affected by a combination of
      environmental drivers. We used a data set of 11 million species occurrence
      records over the period 1970-2010 to assess changes in the frequency of
      occurrence of 673 macro-moth species in Great Britain. Groups of species with
      different predicted sensitivities showed divergent trends, which we interpret in
      the context of land-use and climatic changes.A diversity of responses was
      revealed: 260 moth species declined significantly, whereas 160 increased
      significantly. Overall, frequencies of occurrence declined, mirroring trends in
      less species-rich, yet more intensively studied taxa.Geographically widespread
      species, which were predicted to be more sensitive to land use than to climate
      change, declined significantly in southern Britain, where the cover of urban and
      arable land has increased.Moths associated with low nitrogen and open
      environments (based on their larval host plant characteristics) declined most
      strongly, which is also consistent with a land-use change explanation.Some moths
      that reach their northern (leading edge) range limit in southern Britain
      increased, whereas species restricted to northern Britain (trailing edge)
      declined significantly, consistent with a climate change explanation.Not all
      species of a given type behaved similarly, suggesting that complex interactions
      between species' attributes and different combinations of environmental drivers
      determine frequency of occurrence changes.Synthesis and applications. Our
      findings are consistent with large-scale responses to climatic and land-use
      changes, with some species increasing and others decreasing. We suggest that land
      use change (e.g. habitat loss, nitrogen deposition) and climate change are both
      major drivers of moth biodiversity change, acting independently and in
      combination. Importantly, the diverse responses revealed in this species-rich
      taxon show that multifaceted conservation strategies are needed to minimize
      negative biodiversity impacts of multiple environmental changes. We suggest that
      habitat protection, management and ecological restoration can mitigate combined
      impacts of land-use change and climate change by providing environments that are
      suitable for existing populations and also enable species to shift their ranges.

PMID- 25954053
TI  - Emerging viral disease risk to pollinating insects: ecological, evolutionary and
      anthropogenic factors.
AB  - The potential for infectious pathogens to spillover and emerge from managed
      populations to wildlife communities is poorly understood, but ecological,
      evolutionary and anthropogenic factors are all likely to influence the initial
      exposure and subsequent infection, spread and impact of disease. Fast-evolving
      RNA viruses, known to cause severe colony losses in managed honeybee populations,
      deserve particular attention for their propensity to jump between host species
      and thus threaten ecologically and economically important wild pollinator
      communities. We review the literature on pollinator viruses to identify
      biological and anthropogenic drivers of disease emergence, highlight gaps in the
      literature, and discuss potential management strategies. We provide evidence that
      many wild pollinator species are exposed to viruses from commercial species,
      resulting in multiple spillover events. However, it is not clear whether species
      become infected as a result of spillover or whether transmission is occurring
      within these wild populations. Ecological traits of pollinating insects, such as
      overlapping ranges, niches and behaviours, clearly promote cross-species
      transmission of RNA viruses. Moreover, we conclude that the social behaviour and
      phylogenetic relatedness of social pollinators further facilitate within- and
      between-host transmission, leaving these species particularly vulnerable to
      emerging diseases. We argue that the commercial use of pollinators is a key
      driver of disease emergence in these beneficial insects and that this must be
      addressed by management and policy. Synthesis and applications. There are
      important knowledge gaps, ranging from disease distribution and prevalence, to
      pathogen life history and virulence, to the impacts of disease emergence, which
      need to be addressed as research priorities. It is clear that avoiding
      anthropogenic pathogen spillover is crucial to preventing and managing disease
      emergence in pollinators, with far-reaching effects on our food security,
      ecosystem services and biodiversity. We argue that it is crucial to prevent the
      introduction of diseased pollinators into natural environments, which can be
      achieved through improved monitoring and management practices.

PMID- 25954054
TI  - Reconciling timber extraction with biodiversity conservation in tropical forests
      using reduced-impact logging.
AB  - Over 20% of the world's tropical forests have been selectively logged, and large
      expanses are allocated for future timber extraction. Reduced-impact logging (RIL)
      is being promoted as best practice forestry that increases sustainability and
      lowers CO2 emissions from logging, by reducing collateral damage associated with
      timber extraction. RIL is also expected to minimize the impacts of selective
      logging on biodiversity, although this is yet to be thoroughly tested.We
      undertake the most comprehensive study to date to investigate the biodiversity
      impacts of RIL across multiple taxonomic groups. We quantified birds, bats and
      large mammal assemblage structures, using a before-after control-impact (BACI)
      design across 20 sample sites over a 5-year period. Faunal surveys utilized point
      counts, mist nets and line transects and yielded >250 species. We examined
      assemblage responses to logging, as well as partitions of feeding guild and
      strata (understorey vs. canopy), and then tested for relationships with logging
      intensity to assess the primary determinants of community composition.Community
      analysis revealed little effect of RIL on overall assemblages, as structure and
      composition were similar before and after logging, and between logging and
      control sites. Variation in bird assemblages was explained by natural rates of
      change over time, and not logging intensity. However, when partitioned by feeding
      guild and strata, the frugivorous and canopy bird ensembles changed as a result
      of RIL, although the latter was also associated with change over time. Bats
      exhibited variable changes post-logging that were not related to logging, whereas
      large mammals showed no change at all.Indicator species analysis and correlations
      with logging intensities revealed that some species exhibited idiosyncratic
      responses to RIL, whilst abundance change of most others was associated with
      time.Synthesis and applications. Our study demonstrates the relatively benign
      effect of reduced-impact logging (RIL) on birds, bats and large mammals in a
      neotropical forest context, and therefore, we propose that forest managers should
      improve timber extraction techniques more widely. If RIL is extensively adopted,
      forestry concessions could represent sizeable and important additions to the
      global conservation estate - over 4 million km2.

PMID- 25954055
TI  - Systematically variable planktonic carbon metabolism along a land-to-lake
      gradient in a Great Lakes coastal zone.
AB  - During the summers of 2002-2013, we measured rates of carbon metabolism in
      surface waters of six sites across a land-to-lake gradient from the upstream end
      of drowned river-mouth Muskegon Lake (ML) (freshwater estuary) to 19 km offshore
      in Lake Michigan (LM) (a Great Lake). Despite considerable inter-year
      variability, the average rates of gross production (GP), respiration (R) and net
      production (NP) across ML (604 +/- 58, 222 +/- 22 and 381 +/- 52 ug C L-1 day-1,
      respectively) decreased steeply in the furthest offshore LM site (22 +/- 3, 55 +/
      17 and -33 +/- 15 ug C L-1day-1, respectively). Along this land-to-lake
      gradient, GP decreased by 96 +/- 1%, whereas R only decreased by 75 +/- 9%,
      variably influencing the carbon balance along this coastal zone. All ML sites
      were consistently net autotrophic (mean GP:R = 2.7), while the furthest offshore
      LM site was net heterotrophic (mean GP:R = 0.4). Our study suggests that pelagic
      waters of this Great Lakes coastal estuary are net carbon sinks that transition
      into net carbon sources offshore. Reactive and dynamic estuarine coastal zones
      everywhere may contribute similarly to regional and global carbon cycles.

PMID- 25954056
TI  - Estimating a structured covariance matrix from multi-lab measurements in high
      throughput biology.
AB  - We consider the problem of quantifying the degree of coordination between
      transcription and translation, in yeast. Several studies have reported a
      surprising lack of coordination over the years, in organisms as different as
      yeast and human, using diverse technologies. However, a close look at this
      literature suggests that the lack of reported correlation may not reflect the
      biology of regulation. These reports do not control for between-study biases and
      structure in the measurement errors, ignore key aspects of how the data connect
      to the estimand, and systematically underestimate the correlation as a
      consequence. Here, we design a careful meta-analysis of 27 yeast data sets,
      supported by a multilevel model, full uncertainty quantification, a suite of
      sensitivity analyses and novel theory, to produce a more accurate estimate of the
      correlation between mRNA and protein levels-a proxy for coordination. From a
      statistical perspective, this problem motivates new theory on the impact of
      noise, model mis-specifications and non-ignorable missing data on estimates of
      the correlation between high dimensional responses. We find that the correlation
      between mRNA and protein levels is quite high under the studied conditions, in
      yeast, suggesting that post-transcriptional regulation plays a less prominent
      role than previously thought.

PMID- 25954058
TI  - The Ethics of Producing In Vitro Meat.
AB  - The prospect of consumable meat produced in a laboratory setting without the need
      to raise and slaughter animals is both realistic and exciting. Not only could
      such in vitro meat become popular due to potential cost savings, but it also
      avoids many of the ethical and environmental problems with traditional meat
      productions. However, as with any new technology, in vitro meat is likely to face
      some detractors. We examine in detail three potential objections: 1) in vitro
      meat is disrespectful, either to nature or to animals; 2) it will reduce the
      number of happy animals in the world; and 3) it will open the door to
      cannibalism. While each objection has some attraction, we ultimately find that
      all can be overcome. The upshot is that in vitro meat production is generally
      permissible and, especially for ethical vegetarians, worth promoting.

PMID- 25954057
TI  - Mothers' and Fathers' Sensitivity and Children's Cognitive Development in Low
      Income, Rural Families.
AB  - This study examines associations between maternal and paternal sensitive
      parenting and child cognitive development across the first 3 years of life using
      longitudinal data from 630 families with co-residing biological mothers and
      fathers. Sensitive parenting was measured by observational coding of parent-child
      interactions and child cognitive development was assessed with the Bayley Scales
      of Infant Development and the Wechsler Preschool and Primary Scales of
      Intelligence. There were multiple direct and indirect associations between
      parenting and cognitive development across mothers and fathers, suggesting
      primary effects, carry-forward effects, spillover effects across parents, and
      transactional effects across parents and children. Associations between parenting
      and cognitive development were statistically consistent across mothers and
      fathers, and the cumulative effects of early parenting on later cognitive
      development were comparable to the effects of later parenting on later cognitive
      development. As interpreted through a family systems framework, findings suggest
      additive and interdependent effects across parents and children.

PMID- 25954059
TI  - Optimization of electrooptic and pieozoelectric coupling effects in tetragonal
      relaxor-PT ferroelectric single crystals.
AB  - The electrooptic and piezoelectric coupling effects in tetragonal relaxor-based
      ferroelectric 0.62Pb(Mg1/3Nb2/3)O3-0.38PbTiO3 (PMN-0.38PT) and
      0.88Pb(Zn1/3Nb2/3)O3-0.12PbTiO3 (PZN-0.12PT) single-domain crystals have been
      analyzed by the coordinate transformation. The orientation dependence of the
      electrooptic and half-wave voltage was calculated based on the full sets of
      refractive indices, electrooptic and piezoelectric coefficients. The optimum
      orientation cuts for achieving the best electrooptic coefficient and half-wave
      voltage were found. The lowset half-wave voltage is only 76 V for the PMN-0.38PT
      single-domain crystal. Compared to commonly used electrooptic crystal LiNbO3,
      tetragonal relaxor-PT ferroelectric single-domain crystals are much superior for
      optical modulation applications because of their much higher linear electrooptic
      coefficients and substantially lower half-wave voltages when the piezoelectric
      strain influence is considered.

PMID- 25954060
TI  - A Late Stage Strategy for the Functionalization of Triazolium-based NHC
      catalysts.
AB  - A strategy for the diversification of triazolium-based catalysts is presented.
      This method is based on the reduction to the triazoline, which serves as a
      suitable and stable substrate for Pd-mediated cross-coupling, followed by trityl
      cation mediated reoxidation to the triazolium.

PMID- 25954062
TI  - Comparative evaluation of a new endodontic irrigant - mixture of a tetracycline
      isomer, an Acid, and a detergent to remove the intracanal smear layer: a scanning
      electron microscopic study.
AB  - BACKGROUND: The most important and demanding aspect of endodontic therapy is
      considered to be cleaning and shaping. Irrigation is considered a vital adjunct
      to instrumentation of the root canal for canal debridement. Until date, there is
      no single solution that simultaneously removes the smear layer and disinfects the
      entire root canal system. Thus, this in vitro study was designed to evaluate the
      efficiency of a new irrigation solution mixture of a tetracycline isomer, an
      acid, and a detergent (MTAD) (BioPure, Dentsply) containing a mixture of
      tetracycline (doxycycline hydrochloride), an acid (citric acid) and a detergent
      (Tween 80) in comparison with normal saline, 5% NaOCl and 17%
      ethylenediaminetetraacetic acid (EDTA) to remove intracanal smear layer.
      MATERIALS AND METHODS: A total of 60 single rooted teeth were irrigated with
      Saline (Group A), 5% NaOCl (Group B), 17% EDTA (Group C) and MTDA (Group D). The
      extent of removal of smear layer and erosion was assessed using scanning electron
      microscope. RESULTS: Irrigation with 5% NaOCl and MTAD as a final flush produced
      the cleanest surface with all the dentinal tubules open. No conjugation or
      erosion of dentinal tubules was noted (P > 0.05). CONCLUSION: MTAD flush was the
      most effective debridement regimen in all the three thirds of the canal showing
      its ability to reach the apex with no conjugation and erosion of dentinal
      tubules.

PMID- 25954061
TI  - The role of IL-1beta in the bone loss during rheumatic diseases.
AB  - Several inflammatory diseases have been associated with increased bone resorption
      and fracture rates and different studies supported the relation between
      inflammatory cytokines and osteoclast activity. The main factor required for
      osteoclast activation is the stimulation by receptor activator of nuclear factor
      kappa-B ligand (RANKL) expressed on osteoblasts. In this context, interleukin-
      (IL-) 1beta, one of the most powerful proinflammatory cytokines, is a strong
      stimulator of in vitro and in vivo bone resorption via upregulation of RANKL that
      stimulates the osteoclastogenesis. The resulting effects lead to an imbalance in
      bone metabolism favouring bone resorption and osteoporosis. In this paper, we
      review the available literature on the role of IL-1beta in the pathogenesis of
      bone loss. Furthermore, we analysed the role of IL-1beta in bone resorption
      during rheumatic diseases and, when available, we reported the efficacy of anti
      IL-1beta therapy in this field. 

PMID- 25954063
TI  - Analysis of bond strength by pull out test on fiber glass posts cemented in
      different lengths.
AB  - BACKGROUND: The aim of this study was to evaluate, by means of pull-out test, the
      bond strength of fiberglass posts when cemented with different lengths in
      endodontically treated teeth. MATERIALS AND METHODS: Sixty single-rooted bovine
      roots were cut in the cementoenamel junction with 21 mm length. They were
      endodontically treated and randomly divided into three groups (n = 20). Group 1 -
      Preparation of 2/3 of the remaining roots; Group 2 - Preparation of 1/2 of the
      remaining roots and Group 3 - Preparation of 1/4 of remaining roots. For all
      groups it were used posts n = 3 (Exacto, Angelus, Brazil), and cemented with self
      etching resin cement (RelyXU200). After cementing posts, the samples were
      thermocycled (10.000 cycles/5 degrees C and 55 degrees C). The pull-out test was
      performed on a universal testing machine (EMIC - DL500) and the values obtained
      were statistically analyzed by analysis of variance (one-factor ANOVA) and
      multiple comparison test of Tukey, with level of significance of 5%. RESULTS: The
      mean values +/- standard deviation in Newtons (N) were: Group 1 = 120.5 (+/-42.8)
      A, Group 2 = 103.1 (+/-31.2) AB, Group 3 = 41.2 (+/-22.4) C, P < 0.005.
      CONCLUSION: The preparation of 1/2 of remaining root appears to be a viable
      alternative when 2/3 of the preparation of the remaining root is not possible,
      but more results are needed for clinical validation.

PMID- 25954064
TI  - A Retrospective Radiographic Survey of Pathology Associated with Impacted Third
      Molars among Patients Seen in Oral & Maxillofacial Surgery Clinic of College of
      Dentistry, Riyadh.
AB  - BACKGROUND: The purpose of this study is to determine the type and frequency of
      pathological conditions around third molar teeth among randomly selected
      patient's records in Oral and Maxillofacial Surgery, College of Dentistry, King
      Saud University, Riyadh. MATERIALS AND METHODS: Totally, 281 patient panoramic
      radiographs were selected with detectable pathology among 570 files of patients
      seen in oral and maxillofacial surgery clinics 2 years retrospectively. Almost 17
      55 years age (mean age 25.43) was selected. The following radiographs were
      analyzed for all pathology associated impacted teeth; dental caries, bone
      resorption, periodontitis, and apical pathology. RESULTS: The study found caries,
      external bone resorption and periodontitis are highly frequent to mesioangular
      and horizontal in mandibular impacted third molar compared to maxillary impacted
      third molar. Overall result evaluated that tooth #28 related periodontitis is
      significant (P = 0.021), and tooth #38 related bone resorption, tooth #48 related
      root caries, bone resorption and apical pathology are highly significant (P =
      0.000) comparing to others. This study also concluded the high frequency of root
      caries, bone resorption and apical pathology reported in relation to mandibular
      impacted third teeth. Significant results were also achieved with periodontitis
      in relation to mesiangular and vertical angulation of left impacted maxillary
      third molars. CONCLUSION: Prophylactic removal of impacted third molars is
      recommended in many studies to avoid future risk of associated pathology.
      Retained asymptomatic impacted third molars imply pathology that could be
      difficult in later ages as less morbidity in younger ages.

PMID- 25954065
TI  - Prevalence and attitude of cigarette smoking among Indian expatriates living in
      jeddah, kingdom of saudi arabia.
AB  - BACKGROUND: The objective was to determine the prevalence and attitudes of
      smoking among expatriate Indian workers living in Jeddah, Saudi Arabia. METHODS:
      A cross-sectional analytical study was done. All the data were collected using a
      questionnaire-based interview. RESULTS: A total of 421 people were interviewed.
      Almost half (42%) of the participants were between 31 and 40 years old and 7%
      were over 51 years. The majority of participants (63%) reported to be non
      smokers. The maximum number of smokers was between 41 and 50 years old (42%) and
      most of them were regular smokers. Almost a third of the subjects (30%) had a
      higher secondary level of education, and 7% were illiterate. There was a
      significant association between the prevalence of smoking and the level of
      education (P < 0.001). Among smokers, half of them smoked more than 21
      cigarettes/day. More than half, 238 (57%) of participants agreed that the tobacco
      was harmful to their health, and 50% agreed that tobacco sales should be banned.
      Among all, 92% were concerned about their health and 98% accepted that the
      tobacco causes diseases. The majority of smokers cited stress, loneliness
      financial responsibilities and a lack of socializing as reasons for their smoking
      habit. CONCLUSION: Although the prevalence was relatively high, the majority was
      aware of the harmful effects of smoking and was keen to have the sale of tobacco
      banned. Due to their possible loneliness and stress, many felt that smoking
      helped ease their stress and tension.

PMID- 25954066
TI  - To Evaluate the Bone Mineral Density in Mandible of Edentulous Patients using
      Computed Tomography: An In Vivo Study.
AB  - BACKGROUND: To evaluate the bone mineral density in the mandible of edentulous
      patients at prospective intraoral implant sites. Pre-operative evaluation of bone
      density is essential to assist the clinician with the treatment planning of
      implant supported prosthesis. MATERIALS AND METHODS: A study group of 12
      edentulous subjects comprising of six male and six female between the age group
      of 45-55 years seeking implant supported prosthesis were selected. A radiographic
      stent using auto polymerizing resins incorporating the gutta-percha cones were
      prepared for the computed tomography scan. The bone mineral density values were
      recorded in various sites (trabecular and cortical) of the mandibular jaws in
      Hounsfield units. The data thus obtained were tabulated and statistically
      analyzed using Mann-Whitney U-test and Kruskal-Wallis test. RESULTS: The bone
      mineral density in the buccal cortical region of mandible increases from incisors
      to molars and in the trabecular region it is more in the incisors and canines
      compared to the premolar and molar regions whereas in the lingual cortical region
      of mandible may lie on nearly the same level over the entire lingual cortex. The
      bone mineral density is little higher in males than females. CONCLUSION: There is
      variation in the bone mineral density in the buccal cortex and trabecular bone,
      but no significant variation in the lingual cortex when compared between male and
      female subjects.

PMID- 25954067
TI  - Comparative in vitro evaluation of internal adaptation of resin-modified glass
      ionomer, flowable composite and bonding agent applied as a liner under composite
      restoration: A scanning electron microscope study.
AB  - BACKGROUND: The use of resin-modified glass Ionomer cement in sandwich technique
      is widely practiced with the advent of various newer generation of composites the
      bond between resin-modified glass Ionomer and these resins should be validated.
      This study is done to evaluate the interfacial microgaps between different types
      of liners and dentin, liners and composite (Filtek p60 [FLp60]) using scanning
      electron microscope (SEM). MATERIALS AND METHODS: Standardized Class V
      preparations were performed in buccal/lingual surfaces of 30 caries, crack and
      defect-free extracted human third molars. The prepared teeth were divided into
      three groups. Group I: Single bond (SB), Group II: SB + synergy flow, Group III:
      SB + vitrebond. They were restored with composite resin FLp60, according to the
      manufacturer instructions. The SB + vitrebond, cross-sectioned through the canter
      of the restoration. The specimens were fixed, dehydrated, polished, and processed
      for SEM. The internal adaptation of the materials to the axial wall was analyzed
      under SEM with *1000 magnification. RESULTS: The data obtained were analyzed with
      nonparametric tests (Kruskal-Wallis, P < 0.05). flowable composite or resin
      modified glass ionomer applied in conjunction with adhesive resulted in
      statistically wider microgaps than occurred when the dentin was only hybridized
      prior to the restoration. CONCLUSION: Hybridization of dentin only provides
      superior sealing of the dentin-restoration interface than does flowable resin or
      resin-modified glass ionomer.

PMID- 25954068
TI  - Comparative evaluation of platelet-rich fibrin biomaterial and open flap
      debridement in the treatment of two and three wall intrabony defects.
AB  - BACKGROUND: Platelet-rich concentrates are the most widely used regenerative
      biomaterials. Stimulation and acceleration of soft and hard tissue healing are
      due to local and continuous delivery of growth factors and proteins, mimicking
      the needs of the physiological wound healing and reparative tissue processes.
      This article aims to evaluate the clinical efficacy of open flap debridement
      (OFD) with or without platelet-rich fibrin (PRF) in the treatment of intrabony
      defects. MATERIALS AND METHODS: Twenty subjects with forty intrabony defects were
      treated with either autologous PRF with open-flap debridement (test, n = 20) or
      open-flap debridement alone (control, n = 20). Soft tissue parameters included:
      Plaque index, sulcus bleeding index, probing depth, relative attachment level and
      gingival marginal level (GML). The hard tissue parameters included-distances
      from: Cement enamel junction to the base of the defect (CEJ-BOD): Alveolar crest
      to the base of the defect (AC-BOD): And CEJ to AC. The parameters were recorded
      at baseline and at 9 months postoperatively calculated using standardized
      radiographs by image-analysis software. RESULTS: Statistically significant
      (0.005*) intragroup improvements were seen with all the hard and soft parameters
      in both test and control groups, except for GML. Statistically significant
      improvements were seen with the mean defect fill (CEJ-BOD and AC-BOD) (P =
      0.003*) when intergroup comparisons were made. CONCLUSIONS: Adjunctive use of PRF
      with OFD significantly improves defect fill when compared to OFD alone. PRF has
      consistently been showing regenerative potential; it is simple, easy and
      inexpensive biomaterial compared with bone grafts.

PMID- 25954069
TI  - Role of maxillofacial trauma scoring systems in determining the economic burden
      to maxillofacial trauma patients in India.
AB  - BACKGROUND: The objective of this study was to evaluate the association between
      severity of maxillofacial injuries determined by trauma scoring systems and its
      economic burden to patients in terms of cost and duration of hospitalization.
      MATERIALS AND METHODS: Following ethical approval a retrospective chart review
      was undertaken at Meenakshi Ammal Dental College and Hospital to identify
      patients admitted with maxillofacial injuries between January 2006 and December
      2008. Patients with incomplete records, associated injuries, debilitating
      systemic diseases and patients treated under local anesthesia were excluded.
      Details regarding the nature and severity of injury and treatment were recorded
      in addition to the total treatment cost and duration of hospitalization.
      Maxillofacial injury severity was scored using maxillofacial injury severity
      score (MFISS) and facial injury severity scale (FISS). The MFISS and FISS scores
      were correlated with two surrogate markers of the economic burden namely cost and
      duration of hospitalization. RESULTS: A total of 162 patients with maxillofacial
      injuries were identified (108 males, 54 females; mean age = 32.4 years). Road
      traffic accidents were the cause of injury in 114 patients (70.4%) and only 29
      patients (17.9%) had medical insurance coverage. The mean MFISS and FISS scores
      were 14.04 (standard deviation [SD] = 9.19; range = 3-42) and 4.40 (SD = 3.17;
      range = 1-14), respectively. The mean cost and duration of hospitalization of the
      patients were Indian rupees (INR) 13877.28 (SD = 8252.59; range = INR 5250-42960)
      and 4.12 days (SD = 1.5; range = 2-8 days) respectively. Pearson's correlation
      between the MFISS and FISS scores and the cost and duration of hospitalization,
      revealed statistically significant correlations (MFISS vs. cost - R = 0.862, P <
      0.001; MFISS vs. duration - R = 0.828, P < 0.01; FISS vs. cost - R = 0.845, P <
      0.01; FISS vs. duration - R = 0.819, P < 0.01). CONCLUSION: Based on the results
      of this study, maxillofacial injury severity measured by MFISS and FISS scores
      are predictable indicators of the economic burden to the patients.

PMID- 25954071
TI  - Evaluation of Cellular Phones for Potential Risk of Nosocomial Infection amongst
      Dental Operators and Auxiliary Staff.
AB  - BACKGROUND: This study evaluates cellular phones for potential risk of nosocomial
      infection amongst dental operators and auxiliary staff in a dental school.
      MATERIALS AND METHODS: Each participant's mobile phone was first cleaned with 70%
      isopropyl alcohol swab. Following the cleansing protocol, the partakers were
      asked to make a short phone call. The mobile phones were then washed aseptically
      by rotating damp cotton swabs with sterile normal saline. Bacterial growth was
      identified on sheep blood agar and McConkey's agar plates. Sabouraud dextrose
      agar media was used for fungi species. Descriptive statistics was established
      with the data statistically explored with SPSS version 17.0. RESULTS: About 50%
      of dental professionals had shown active bacterial and fungal growth in which 35%
      (n=35) were dental operators and 15% (n=15) were dental nurses. 53% Gram-positive
      organisms, 2% Gram-negative organisms, and 3% fungi were identified growths on
      cellular phones. CONCLUSION: Thus, it can be concluded that the cellular phones
      of dental operators as compared to auxiliaries can act as a potential source of
      nosocomial infection.

PMID- 25954070
TI  - Long term stability following genioplasty: a cephalometric study.
AB  - BACKGROUND: A receding chin associated with an orthognathic mandible is a common
      situation and surgical changes in chin position are often required to improve the
      overall harmony of the face. Genioplasty is one such procedure. Stability of hard
      and soft tissue changes following genioplasty on a long term basis needs to be
      assessed. Studies on the stability of hard and soft tissue changes following
      genioplasty on a short term basis have revealed it as a procedure with good
      stability. This study is done to assess the stability of hard and soft tissue
      changes following genioplasty on a long term basis. MATERIALS AND METHODS: Pre
      surgical, postsurgical and long term post-surgical cephalograms of 15 cases
      treated by vertical reduction augmentation genioplasty were obtained. Paired t
      test was used to compare the changes between pre-surgical, postsurgical and long
      term postsurgical cephalograms. RESULTS: Findings of this study demonstrated that
      genioplasty is a stable procedure. After long term follow-up period, there was a
      relapse of 1.5 mm at the pogonion accounting for 24% of the surgical advancement.
      This is attributed to the remodeling that occurs at the surgical site, but not
      the instability due to the surgical procedure. CONCLUSION: With the present
      study, it can be concluded that vertical reduction and advancement genioplasty
      can be considered as an adjunctive procedure that produces predictable results
      and the bony and soft tissue stability were generally very good.

PMID- 25954072
TI  - Antimicrobial activity of filling materials used in primary teeth pulpotomy.
AB  - The aim of this study was to investigate the antibacterial activity of pulp
      capping materials used in primary teeth (formocresol [FC], zinc oxide and eugenol
      cement [ZOE], ZOE mixed with FC [ZOEFC], mineral trioxide aggregate [MTA] and
      calcium hydroxide [CH]) against cariogenic bacteria. The agar plate diffusion
      test was used for the cultures, including saline solution as a negative control.
      A base layer of 15 mL of brain heart infusion agar was inoculated with 300 mL of
      each inoculum. Twelve wells were made and completely filled with one of the
      testing materials for each bacteria strain. The plates were incubated at 37
      degrees C for 48 h. Zones of microbial inhibition and material diffusion were
      measured and photographed. The results obtained were analyzed by Kruskal-Wallis
      and Mann-Whitney non-parametric tests. Respectively, the medium zones of bacteria
      inhibition of FC, ZOE, ZOEFC, MTA and CH against Streptococcus mutans growth were
      28.5, 15.2, 20.8, 9.3 and 11.6; against Lactobacillus acidophilus growth were
      28.7, 14.8, 15.3, 15.2 and 20.0, and against Actinomyces viscosus growth were
      13.6, 13.5, 14.7, 10.0 and 13.6. We might confirmed the high antibacterial
      activity of FC solution, especially against S. mutans and L. acidophilus, as
      wells as, the low inhibitory effect of MTA cement on the cariogenic bacteria
      studied. 

PMID- 25954073
TI  - An evaluation of pathologic changes in the follicle of impacted mandibular third
      molars.
AB  - BACKGROUND: The purpose of this study was to evaluate the early pathologic
      changes in the follicular tissue of completely impacted mandibular third molar.
      MATERIALS AND METHODS: 52 patients, between 18 and 52 years of age of which 25
      were males and 27 were females, were selected. They had impacted mandibular third
      molars, which were indicated for extraction. After extraction, the follicle was
      sent for a histopathological evaluation to two different oral pathologists.
      RESULTS: The results showed that 80.8% of the specimen had normal follicles.
      11.5% specimen suggested cystic changes while 7.7% suggested infected follicle.
      CONCLUSION: It is desirable to consider prophylactic removal of impacted
      mandibular third molar presenting at a younger age, whereas their removal remains
      an enigma for the older age group and should only be considered appropriate in
      those cases where frank causes for its removal are established.

PMID- 25954074
TI  - Comparative Evaluation of Effect of Water Absorption on the Surface Properties of
      Heat Cure Acrylic: An in vitro Study.
AB  - BACKGROUND: Use of alkaline peroxide denture cleanser with different temperature
      of water could cause a change in surface hardness of the acrylic denture and also
      has a bleaching effect. The purpose of the study was to determine the effect of
      increased water content during thermal cycling of hot water-treated acrylic on
      the surface hardness of acrylic denture base when compared to warm water treated
      acrylic. And to compare the bleaching effect of alkaline peroxide solution on the
      acrylic denture base on hot water and warm water treated acrylic. MATERIALS AND
      METHODS: Forty samples (10 mm * 10 mm * 2.5 mm) were prepared. After the
      calculation of the initial hardness 40 samples, each was randomly assigned to two
      groups. Group A: 20 samples were immersed in 250 ml of warm distilled water at 40
      degrees C with alkaline peroxide tablet. Group B: 20 samples were immersed in 250
      ml of hot distilled water at 100 degrees C with alkaline peroxide tablet. The
      surface hardness of each test sample was obtained using the digital hardness
      testing machine recording the Rockwell hardness number before the beginning of
      the soaking cycles and after completion of 30 soak cycles and compared. Values
      were analyzed using paired t-test. Five samples from the Group A and five samples
      from Group B were put side by side and photographed using a Nikon D 40 digital
      SLR Camera and the photographs were examined visually to assess the change in
      color. RESULTS: Acrylic samples immersed in hot water showed a statistically
      significant decrease of 5.8% in surface hardness. And those immersed in warm
      water showed a statistically insignificant increase of 0.67% in surface hardness.
      Samples from the two groups showed clinically insignificant difference in color
      when compared to each other on examination of the photographs. CONCLUSION:
      Thermocycling of the acrylic resin at different water bath temperature at 40
      degrees C and 100 degrees C showed significant changes in the surface hardness.

PMID- 25954075
TI  - Emotional Intelligence among Dental Undergraduate Students: An Indispensable and
      Ignored Aspect in Dentistry.
AB  - BACKGROUND: Emotional intelligence (EI) is a measure of pure intelligence of
      cognitive ability that translates psychological knowledge into terms that are
      useable by people not professionally trained in psychology, like dentists.
      MATERIALS AND METHODS: A cross-sectional, self-administered, structured
      questionnaire survey in English was distributed among 186 undergraduate students
      to assess their EI. It consisted of 30 questions, 5 each to assess the self
      awareness, empathy, self-confidence, motivation, social control, and self
      competency. All the participants were asked to answer each question, anything
      between virtually never to virtually always using the rating scale 1-5. RESULTS:
      The collected data were analyzed using statistical software SPSS version 20
      (Chicago, Inc.). The mean, median, and mode for various responses between the
      groups were compared. Only 11.55% of the participants had good EI with scores
      above 20 in all domains, while a majority of 54.02% proved to have average EI. A
      mere 2.05% showed to have very poor EI and 28.84% demonstrated poor EI.
      CONCLUSIONS: The study showed that only 11.55% had a good EI and a major
      percentage of the students require immediate intervention to improve their EI.

PMID- 25954076
TI  - Prospective analysis of secondary alveolar bone grafting in cleft lip and palate
      patients.
AB  - BACKGROUND: To assess the success of the uptake of bone graft in cleft alveolus
      of the cleft lip and palate patients, quantitatively through computed tomography
      (CT) scan 6 months postoperative. To assess the successful eruption of permanent
      lateral incisor or canine in the bone grafted area. MATERIALS AND METHODS: The
      children age group of 9-21 years with unilateral cleft lip and palate came to the
      hospital, needing secondary alveolar bone grafting. A detailed history and
      clinical examination of the patient was taken. A 3D CT scan was taken and the
      volume of the cleft was measured pre-operatively. After ambulatory period, 3D CT
      scan of the alveolar cleft region was taken and volume of the bone grafted was
      measured and patient was discharged from the hospital. After 6 months, patient
      was recalled and again 3D CT scan was taken and the volume of remaining bone was
      measured. RESULTS: The mean volume of the defect pre-operatively is 0.80 cm(3)
      with a standard deviation of 0.36 cm(3) with minimum volume of the defect 0.44
      cm(3) and maximum volume of the defect 1.60 cm(3). The mean volume of the bone
      post-operative immediately after grafting is 1.01 cm(3) with a standard deviation
      of 0.52 cm(3) with minimum of bone volume is 0.48 cm(3) and maximum of 2.06
      cm(3). The mean volume of the bone after 6 months after bone grafting is 0.54
      cm(3) with a standard deviation of 0.33 cm(3), minimum bone volume of 0.22 cm(3)
      and maximum bone volume of 1.42 cm(3). CONCLUSION: The CT scan is a valuable
      radiographic imaging modality to assess and follow the clinical outcome of
      secondary alveolar bone grafting.

PMID- 25954077
TI  - Consanguineous Marital Union Resulting in a Progeny of Whistling-face Syndrome
      and Hemophilia: A Case Report.
AB  - Many different types of genetic disorders are noted to be prevalent among
      consanguineous progeny. Although the most common type of consanguineous union in
      all major societies is between first cousins, the importance of customary
      influences is apparent from variations in the specific types of first-cousin
      marriages contracted. Epidemiological data for the prevalence of whistling-face
      syndrome (WFS) are not available, but less than a hundred cases reported in the
      literature are noted. We are presenting a case where a consanguineous marriage
      resulted in two of their children presenting with WFS and one with hemophilia. 

PMID- 25954078
TI  - Prosthetic Rehabilitation of a Patient with Ocular Defect using Semi-customized
      Prosthesis: A Case Report.
AB  - Severe physical and psychological distress occurs due to disfigurement caused by
      loss of eye. Ocular prosthesis is the only mode of rehabilitation for the missing
      eye. There are different materials and techniques used for the fabrication of the
      same. Resin proved to be the better among the available materials. Either using
      the stock eye or using customized ocular prosthesis has their own advantages and
      disadvantages. Through our clinical report, we have fabricated a semi-customized
      ocular prosthesis with stock iris and customized sclera. This prosthesis had the
      advantages of both stock and custom ocular prosthesis providing functionally and
      esthetically satisfactory result. 

PMID- 25954079
TI  - Damaging oral habits.
AB  - Oral habits, if persist beyond certain developmental age, can pose great harm to
      the developing teeth, occlusion, and surrounding oral tissues. In the formative
      years, almost all children engage in some non-nutritive sucking habits.
      Clinicians, by proper differential diagnosis and thorough understanding of
      natural growth and developmental processes, should take a decision for
      intervening. This article describes case series reports of thumb sucking, finger
      sucking, and tongue thrusting habits, which have been successfully treated by
      both removable and fixed orthodontic appliances. The cases shown are ranging from
      the age group of 9-19 years presenting combination of both mixed and permanent
      dentition development. All cases show satisfactory correction of habits and
      stable results. 

PMID- 25954080
TI  - Multidisciplinary approach to the management of complicated crown-root fracture:
      a case report.
AB  - Oblique crown-root fracture in the cervical third of the root is a common event
      following trauma to the anterior region of the mouth. As a result, sound tooth
      structure coronal to the attachment apparatus may not be available for
      restorative needs. Invasion of biological width by fracture line presents a
      clinical challenge in restorative planning. Placing a restoration margin on sound
      tooth structure within the dentogingival biological width might result in
      violation of biological width and should be considered a restorative failure.
      Maintaining a healthy periodontal attachment apparatus is crucial for long term
      prognosis and esthetics of the restored tooth. Surgical crown lengthening,
      surgical extrusion or orthodontic extrusions are the few alternative modalities
      to expose the fracture line. This case presentation demonstrates a predictable
      solution in overcoming an oblique crown-root fracture caused by trauma during a
      road accident. Orthodontic extrusion was used to elevate the fractured tooth from
      within the alveolar socket to allow the placement of crown margins on sound tooth
      structure without harming the biologic width. Combining fiberotomy with the
      extrusion procedure in this case eliminated the need for the surgical procedure.
      This allowed proper fabrication of post and core and the placement of the crown
      on sound tooth structure, fulfilling the biological and mechanical principles
      including obligatory ferrule effect. 

PMID- 25954081
TI  - Treatment guidelines and prognosis of immune reconstitution inflammatory syndrome
      patients: a review.
AB  - Immune reconstitution inflammatory syndrome (IRIS) is an "unmasking" or
      paradoxical worsening of a pre-existing infection after commencement of highly
      active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV) -
      infected patients. The use of HAART in the management of HIV patients restores
      immune responses against pathogens however in few patients, the reconstituted
      immune system leads to IRIS. As the treatment protocols are not standardized for
      IRIS, this leads to short-term morbidity or in some cases also mortality.
      Therefore, treatment in these patients is a huge challenge and further more
      research regarding the immunopathogenesis, diagnosis and management of IRIS
      should be well thought-out. To understand the immunopathogenesis of IRIS it will
      be difficult to elucidate the intrinsic dynamics of immune cells after initiation
      of HAART but, there are few biomarkers which help to predict or diagnose IRIS and
      develop specific treatment, following initiation of HIV therapy. This review is
      an attempt to put light on those patients with IRIS with treatment guidelines for
      the management of the progression of it. 

PMID- 25954083
TI  - DNA methylation induced epigenetic silencing: a potential biomarker and
      therapeutic target for head and neck squamous cell carcinoma.

PMID- 25954082
TI  - Assessment of Chair-side Computer-Aided Design and Computer-Aided Manufacturing
      Restorations: A Review of the Literature.
AB  - BACKGROUND: This paper aimed to evaluate the application of computer-aided design
      and computer-aided manufacturing (CAD-CAM) technology and the factors that affect
      the survival of restorations. MATERIALS AND METHODS: A thorough literature search
      using PubMed, Medline, Embase, Science Direct, Wiley Online Library and Grey
      literature were performed from the year 2004 up to June 2014. Only relevant
      research was considered. RESULTS: The use of chair-side CAD/CAM systems is
      promising in all dental branches in terms of minimizing time and effort made by
      dentists, technicians and patients for restoring and maintaining patient oral
      function and aesthetic, while providing high quality outcome. CONCLUSION: The way
      of producing and placing the restorations made with the chair-side CAD/CAM (CEREC
      and E4D) devices is better than restorations made by conventional laboratory
      procedures.

PMID- 25954084
TI  - Review on hepatic explant pathology of pediatric intestinal transplant
      recipients: Is it time for an oil change?
AB  - A recent study attempts to add to the body of evidence that is emerging regarding
      the fish oil parenteral lipid product OmegavenTM. The authors have shown from
      explant livers of children on chronic parenteral nutrition with OmegavenTM that
      biochemical improvement in cholestasis does not always reflect improvement in
      liver histology. These findings support 2 small case series that were previously
      published. Despite improvement and resolution of hyperbilirubinemia in all six
      infants, five of six infants had persistent or progressive hepatic fibrosis,
      while only one infant had regression of fibrosis. The study raises questions of
      whether there is a window of opportunity for efficacy of this preparation; also,
      an important question is if this omega-3 fatty acid-rich preparation is superior
      to newer "blended lipids" containing olive, coconut, soy, and fish oil. 

PMID- 25954085
TI  - Wireless endoscopy in 2020: Will it still be a capsule?
AB  - Currently, the major problem of all existing commercial capsule devices is the
      lack of control of movement. In the future, with an interface application, the
      clinician will be able to stop and direct the device into points of interest for
      detailed inspection/diagnosis, and therapy delivery. This editorial presents
      current commercially-available new designs, European projects and delivery
      capsule and gives an overview of the progress required and progress that will be
      achieved -according to the opinion of the authors- in the next 5 year leading to
      2020.

PMID- 25954086
TI  - Liver plays a central role in asymmetric dimethylarginine-mediated organ injury.
AB  - Asymmetric-dimethylarginine (ADMA) competes with L-arginine for each of the three
      isoforms of nitric oxide synthase: endothelial; neuronal; inducible. ADMA is
      synthesized by protein methyltransferases followed by proteolytic degradation.
      ADMA is metabolized to citrulline and dimethylamine, by dimethylarginine
      dimethylaminohydrolase (DDAH) and enters cells through cationic amino-acid
      transporters extensively expressed in the liver. The liver plays a crucial role
      in ADMA metabolism by DDAH-1 and, as has been recently demonstrated, it is also
      responsible for ADMA biliary excretion. A correlation has been demonstrated
      between plasma ADMA levels and the degree of hepatic dysfunction in patients
      suffering from liver diseases with varying aetiologies: plasma ADMA levels are
      increased in patients with liver cirrhosis, alcoholic hepatitis and acute liver
      failure. The mechanism by which liver dysfunction results in raised ADMA
      concentrations is probably due to impaired activity of DDAH due to severe
      inflammation, oxidative stress, and direct damage to DDAH. High plasma ADMA
      levels are also relevant as they are associated with the onset of multi-organ
      failure (MOF). Increased plasma concentration of ADMA was identified as an
      independent risk factor for MOF in critically-ill patients causing enhanced
      Intensive Care Unit mortality: a significant reduction in nitric oxide synthesis,
      leading to malperfusion in various organs, eventually culminating in multi organs
      dysfunction. 

PMID- 25954087
TI  - Reversibility and heritability of liver fibrosis: Implications for research and
      therapy.
AB  - Liver fibrosis continues to be a major health problem worldwide due to lack of
      effective therapy. If the etiology cannot be eliminated, liver fibrosis
      progresses to cirrhosis and eventually to liver failure or malignancy; both are
      associated with a fatal outcome. Liver transplantation, the only curative
      therapy, is still mostly unavailable. Liver fibrosis was shown to be a reversible
      process; however, complete reversibility remains debatable. Recently, the
      molecular markers of liver fibrosis were shown to be transmitted across
      generations. Epigenetic mechanisms including DNA methylation, histone
      posttranslational modifications and noncoding RNA have emerged as major
      determinants of gene expression during liver fibrogenesis and carcinogenesis.
      Furthermore, epigenetic mechanisms have been shown to be transmitted through
      mitosis and meiosis to daughter cells and subsequent generations. However, the
      exact epigenetic regulation of complete liver fibrosis resolution and inheritance
      has not been fully elucidated. This communication will highlight the recent
      advances in the search for delineating the mechanisms governing resolution of
      liver fibrosis and the potential for multigenerational and transgenerational
      transmission of fibrosis markers. The fact that epigenetic changes, unlike
      genetic mutations, are reversible and can be modulated pharmacologically
      underscores the unique opportunity to develop effective therapy to completely
      reverse liver fibrosis, to prevent the development of malignancy and to regulate
      heritability of fibrosis phenotype. 

PMID- 25954088
TI  - Non-polypoid colorectal neoplasms: Classification, therapy and follow-up.
AB  - In the last years, an increasing interest has been raised on non-polypoid
      colorectal tumors (NPT) and in particular on large flat neoplastic lesions beyond
      10 mm tending to grow laterally, called laterally spreading tumors (LST). LSTs
      and large sessile polyps have a greater frequency of high-grade dysplasia and
      local invasiveness as compared to pedunculated lesions of the same size and
      usually represent a technical challenge for the endoscopist in terms of either
      diagnosis and resection. According to the Paris classification, NPTs are
      distinguished in slightly elevated (0-IIa, less than 2.5 mm), flat (0-IIb) or
      slightly depressed (0-IIc). NPTs are usually flat or slightly elevated and tend
      to spread laterally while in case of depressed lesions, cell proliferation growth
      progresses in depth in the colonic wall, thus leading to an increased risk of
      submucosal invasion (SMI) even for smaller neoplasms. NPTs may be frequently
      missed by inexperienced endoscopists, thus a careful training and precise
      assessment of all suspected mucosal areas should be performed. Chromoendoscopy
      or, if possible, narrow-band imaging technique should be considered for the
      estimation of SMI risk of NPTs, and the characterization of pit pattern and
      vascular pattern may be useful to predict the risk of SMI and, therefore, to
      guide the therapeutic decision. Lesions suitable to endoscopic resection are
      those confined to the mucosa (or superficial layer of submucosa in selected
      cases) whereas deeper invasion makes endoscopic therapy infeasible. Endoscopic
      mucosal resection (EMR, piecemeal for LSTs > 20 mm, en bloc for smaller
      neoplasms) remains the first-line therapy for NPTs, whereas endoscopic submucosal
      dissection in high-volume centers or surgery should be considered for large LSTs
      for which en bloc resection is mandatory and cannot be achieved by means of EMR.
      After piecemeal EMR, follow-up colonoscopy should be performed at 3 mo to assess
      resection completeness. In case of en bloc resection, surveillance colonoscopy
      should be scheduled at 3 years for adenomatous lesions >= 1 cm, or in presence of
      villous features or high-grade dysplasia patients (regardless of the size), while
      less intensive surveillance (colonoscopy at 5-10 years) is needed in case of
      single (or two) NPT < 1 cm presenting tubular features or low-grade dysplasia at
      histology. 

PMID- 25954089
TI  - Chemotherapy for colorectal cancer in the elderly.
AB  - Colorectal cancer (CRC) is one of the leading causes of cancer-related death in
      the elderly. However, elderly patients with CRC tend to be under-presented in
      clinical trials and undertreated in clinical practice. Advanced age alone should
      not be the only criteria to preclude effective therapy in elderly patients with
      CRC. The best guide about optimal cancer treatment can be provided by
      comprehensive geriatric assessment. Elderly patients with stage III colon cancer
      can enjoy the same benefit from adjuvant chemotherapy with 5
      fluorouracil/leucovorin or capecitabine as younger patients, without a
      substantial increase in toxicity. With conflicting results of retrospective
      studies and a lack of data available from randomized studies, combined modality
      treatment should be used with great caution in elderly patients with locally
      advanced rectal cancer. Combination chemotherapy can be considered for older
      patients with metastatic CRC. For elderly patients who are frail or vulnerable,
      however, monotherapy or a stop-and-go strategy may be desirable. The use of
      targeted therapies in older patients with metastatic CRC appears to be promising
      in view of their better efficacy and toxicity. Treatment should be individualized
      based on the nature of the disease, the physiologic or functional status, and the
      patient's preference. 

PMID- 25954090
TI  - Sex- and gender-specific disparities in colorectal cancer risk.
AB  - Colorectal cancer is one of the most common causes of cancer morbidity both in
      men and in women. However, females over 65 years old show higher mortality and
      lower 5-year survival rate of colorectal cancer compared to their age-matched
      male counterparts. The objective of this review is to suggest gender-based
      innovations to improve colorectal cancer outcomes in females. Women have a higher
      risk of developing right-sided (proximal) colon cancer than men, which is
      associated with more aggressive form of neoplasia compared to left-sided (distal)
      colon cancer. Despite differences in tumor location between women and men, most
      of scientific researchers do not consider sex specificity for study design and
      interpretation. Also, colorectal cancer screening guidelines do not distinguish
      females from male, which may explain the higher frequency of more advanced
      neoplasia when tumors are first detected and false negative results in
      colonoscopy in females. Moreover, socio-cultural barriers within females are
      present to delay screening and diagnosis. Few studies, among studies that
      included both men and women, have reported sex-specific estimates of dietary risk
      factors which are crucial to establish cancer prevention guidelines despite sex-
      and gender-associated differences in nutrient metabolism and dietary practices.
      Furthermore, anti-cancer drug use for colorectal cancer treatment can cause
      toxicity to the reproductive system, and gender-specific recurrence and survival
      rates are reported. Therefore, by understanding sex- and gender-related
      biological and socio-cultural differences in colorectal cancer risk, gender
      specific strategies for screening, treatment and prevention protocols can be
      established to reduce the mortality and improve the quality of life. 

PMID- 25954091
TI  - Learning models for endoscopic ultrasonography in gastrointestinal endoscopy.
AB  - Endoscopic ultrasonography (EUS) has become a useful diagnostic and therapeutic
      modality in gastrointestinal endoscopy. However, EUS requires additional training
      since it requires simultaneous endoscopic manipulation and ultrasonographic
      interpretation. Obtaining adequate EUS training can be challenging since EUS is
      highly operator-dependent and training on actual patients can be associated with
      an increased risk of complications including inaccurate diagnosis. Therefore,
      several models have been developed to help facilitate training of EUS. The models
      currently available for EUS training include computer-based simulators, phantoms,
      ex vivo models, and live animal models. Although each model has its own merits
      and limitations, the value of these different models is rather complementary than
      competitive. However, there is a lack of objective data regarding the efficacy of
      each model with recommendations on the use of various training models based on
      expert opinion only. Therefore, objective studies evaluating the efficacy of
      various EUS training models on technical and clinical outcomes are still needed. 

PMID- 25954092
TI  - Advances in understanding and treating liver diseases during pregnancy: A review.
AB  - Liver disease in pregnancy is rare but pregnancy-related liver diseases may cause
      threat to fetal and maternal survival. It includes pre-eclampsia; eclampsia;
      haemolysis, elevated liver enzymes, and low platelets syndrome; acute fatty liver
      of pregnancy; hyperemesis gravidarum; and intrahepatic cholestasis of pregnancy.
      Recent basic researches have shown the various etiologies involved in this
      disease entity. With these advances, rapid diagnosis is essential for severe
      cases since the decision of immediate delivery is important for maternal and
      fetal survival. The other therapeutic options have also been shown in recent
      reports based on the clinical trials and cooperation and information sharing
      between hepatologist and gynecologist is important for timely therapeutic
      intervention. Therefore, correct understandings of diseases and differential
      diagnosis from the pre-existing and co-incidental liver diseases during the
      pregnancy will help to achieve better prognosis. Therefore, here we review and
      summarized recent advances in understanding the etiologies, clinical courses and
      management of liver disease in pregnancy. This information will contribute to
      physicians for diagnosis of disease and optimum management of patients. 

PMID- 25954093
TI  - Role of vitamins in gastrointestinal diseases.
AB  - A tremendous amount of data from research was published over the past decades
      concerning the roles of different vitamins in various gastrointestinal diseases.
      For instance, most vitamins showed an inverse relationship with the risk of
      colorectal carcinoma as well as other malignancies like gastric and esophageal
      cancer in observational trials, however interventional trials failed to prove a
      clear beneficial preventive role. On the other hand, more solid evidence was
      obtained from high quality studies for a role of certain vitamins in specific
      entities. Examples for this include the therapeutic role of vitamin E in patients
      with non-alcoholic steatohepatitis, the additive role of vitamins B12 and D to
      the standard therapy of chronic hepatitis C virus, the role of vitamin C in
      reducing the risk of gallstones, the positive outcome with vitamin B12 in
      patients with aphthous stomatitis, and the beneficial effect of vitamin D and B1
      in patients with inflammatory bowel disease. Other potential uses are yet to be
      elaborated, like those on celiac disease, pancreatic cancer, pancreatitis,
      cholestasis and other potential fields. Data from several ongoing interventional
      trials are expected to add to the current knowledge over the coming few years.
      Given that vitamin supplementation is psychologically accepted by patients as a
      natural compound with relative safety and low cost, their use should be
      encouraged in the fields where positive data are available. 

PMID- 25954094
TI  - From reflux esophagitis to Barrett's esophagus and esophageal adenocarcinoma.
AB  - The occurrence of gastroesophageal reflux disease is common in the human
      population. Almost all cases of esophageal adenocarcinoma are derived from
      Barrett's esophagus, which is a complication of esophageal adenocarcinoma
      precancerous lesions. Chronic exposure of the esophagus to gastroduodenal
      intestinal fluid is an important determinant factor in the development of
      Barrett's esophagus. The replacement of normal squamous epithelium with specific
      columnar epithelium in the lower esophagus induced by the chronic exposure to
      gastroduodenal fluid could lead to intestinal metaplasia, which is closely
      associated with the development of esophageal adenocarcinoma. However, the exact
      mechanism of injury is not completely understood. Various animal models of the
      developmental mechanisms of disease, and theoretical and clinical effects of drug
      treatment have been widely used in research. Recently, animal models employed in
      studies on gastroesophageal reflux injury have allowed significant progress. The
      advantage of using animal models lies in the ability to accurately control the
      experimental conditions for better evaluation of results. In this article,
      various modeling methods are reviewed, with discussion of the major findings on
      the developmental mechanism of Barrett's esophagus, which should help to develop
      better prevention and treatment strategies for Barrett's esophagus. 

PMID- 25954095
TI  - Roles of long non-coding RNAs in gastric cancer metastasis.
AB  - Gastric cancer is the second leading cause of cancer-related deaths. Metastasis,
      which is an important element of gastric cancer, leads to a high mortality rate
      and to a poor prognosis. Gastric cancer metastasis has a complex progression that
      involves multiple biological processes. The comprehensive mechanisms of
      metastasis remain unclear, though traditional regulation modulates the molecular
      functions associated with metastasis. Long non-coding RNAs (lncRNAs) have a role
      in different gene regulatory pathways by epigenetic modification and by
      transcriptional and post-transcription regulation. lncRNAs participate in various
      diseases, including Alzheimer's disease, cardiovascular disease, and cancer. The
      altered expressions of certain lncRNAs are linked to gastric cancer metastasis
      and invasion, as with tumor suppressor genes or oncogenes. Studies have partly
      elucidated the roles of lncRNAs as biomarkers and in therapies, as well as their
      gene regulatory mechanisms. However, comprehensive knowledge regarding the
      functional mechanisms of gene regulation in metastatic gastric cancer remains
      scarce. To provide a theoretical basis for therapeutic intervention in metastatic
      gastric cancer, we reviewed the functions of lncRNAs and their regulatory roles
      in gastric cancer metastasis. 

PMID- 25954097
TI  - Novel isolated cecal pouch model for endoscopic observation in rats.
AB  - AIM: To create a new rat model for drug administration, cell transplantation, and
      endoscopic examination for the treatment of intestinal diseases. METHODS:
      F344/NJc l-rnu/rnu rats (10-wk-old males, 350-400 g) were used in this study. The
      rats were anesthetized via 2% isoflurane inhalation. The rat's cecum was isolated
      from the intestines, and a pouch was created. The remainder of the intestines was
      rejoined to create an anastomosis. The "side-to-side" anastomosis (SSA) technique
      initially involves the creation of a 2-cm longitudinal incision into each
      intestinal wall. To create an anastomosis along the ileal and colonic walls, both
      intestines were cut, and a continuous suture procedure was performed that
      included all layers of both intestines. The serous membrane was sutured along the
      edge and on the anterior wall of the anastomosis. The "end-to-end" anastomosis
      (EEA) technique was compared with the SSA technique. In the EEA technique, the
      frontal surfaces of both cut intestinal lumens were joined together by continuous
      sutures. Additional sutures were made at the serosa. After the anastomotic
      intestine was successfully constructed, the two intestinal lumens that were cut
      at the isolated cecum were managed. In addition, one luminal side of the pouch
      remained open to create an artificial anus on the dorsum as a passage for the
      residual substances in the pouch. Finally, small animal endoscopy was used to
      observe the inside of the pouch. RESULTS: In this animal model, mucus and feces
      are excreted through the reconstructed passage. Accordingly, the cecal pouch
      mucosa was not obstructed or contaminated by feces, thus facilitating
      observations of the luminal surface of the intestine. The endoscopic observation
      of the cecal pouch provided clear visualization given the absence of feces. The
      membrane surface of the cecum was clearly observed. Two methods of creating an
      anastomotic intestine, the "SSA" and "EEA" techniques, were compared with regard
      to animal survival rate, complication rate, and operation time. The SSA technique
      resulted in a significantly increased survival rate and a lower incidence of
      complications in rat models compared with the EEA technique. The complications of
      stenosis and leakage resulted in death in the EEA technique. Thus, the EEA
      technique exhibited a lower survival rate compared with the SSA technique.
      However, the SSA technique required a significantly longer operation time
      compared with the EEA technique. CONCLUSION: Our new rat model is potentially
      useful for the development of a novel treatment for intestinal diseases.

PMID- 25954098
TI  - Autophagy in anti-apoptotic effect of augmenter of liver regeneration in HepG2
      cells.
AB  - AIM: To investigate the role of autophagy in the anti-apoptotic effect of
      augmenter of liver regeneration (ALR). METHODS: Autophagy was induced through
      serum deprivation. An ALR-expressing plasmid was transfected into HepG2 cells,
      and autophagic flux was determined using fluorescence microscopy, electron
      microscopy, Western blot and quantitative polymerase chain reaction (qPCR)
      assays. After ALR-expressing plasmid transfection, an autophagy inhibitor [3
      methyladenine (3-MA)] was added to HepG2 cells, and apoptosis was observed using
      fluorescence microscopy and flow cytometry. RESULTS: Autophagy was activated in
      HepG2 cells, peaking at 24 h after serum deprivation. Microtubule-associated
      protein light chain three-II levels were higher in HepG2 cells treated with ALR
      than in control cells, fluorescence microscopy, electron microscopy and qPCR
      studies showed the similar trend, and p62 levels showed the opposite trend, which
      indicated that ALR may play an important role in increasing autophagy flux. The
      numbers of apoptotic cells were substantially higher in HepG2 cells treated with
      both ALR and 3-MA than in cells treated with ALR alone. Therefore, the protective
      effect of ALR was significantly attenuated or abolished when autophagy was
      inhibited, indicating that the anti-apoptotic effect of ALR may be related to
      autophagy. CONCLUSION: ALR protects cells from apoptosis partly through increased
      autophagy in HepG2 cells and may be valuable as a new therapeutic treatment for
      liver disease.

PMID- 25954096
TI  - Ultrasonographic imaging of inflammatory bowel disease in pediatric patients.
AB  - Inflammatory bowel disease (IBD) is one of the most common chronic
      gastrointestinal diseases in pediatric patients. Choosing the optimal imaging
      modality for the assessment of gastrointestinal disease in pediatric patients can
      be challenging. The invasiveness and patient acceptance, the radiation exposure
      and the quality performance of the diagnostic test need to be considered. By
      reviewing the literature regarding imaging in inflammatory bowel disease the
      value of ultrasound in the clinical management of pediatric patients is
      highlighted. Transabdominal ultrasound is a useful, noninvasive method for the
      initial diagnosis of IBD in children; it also provides guidance for therapeutic
      decisions and helps to characterize and predict the course of the disease in
      individual patients. Ultrasound techniques including color Doppler imaging and
      contrast-enhanced ultrasound are promising imaging tools to determine disease
      activity and complications. Comparative studies between different imaging methods
      are needed. 

PMID- 25954099
TI  - Low contrast medium and radiation dose for hepatic computed tomography perfusion
      of rabbit VX2 tumor.
AB  - AIM: To evaluate the feasibility of low contrast medium and radiation dose for
      hepatic computed tomography (CT) perfusion of rabbit VX2 tumor. METHODS: Eleven
      rabbits with hepatic VX2 tumor underwent perfusion CT scanning with a 24-h
      interval between a conventional tube potential (120 kVp) protocol with 350 mgI/mL
      contrast medium and filtered back projection, and a low tube potential (80 kVp)
      protocol with 270 mgI/mL contrast medium with iterative reconstruction.
      Correlation and agreement among perfusion parameters acquired by the conventional
      and low dose protocols were assessed for the viable tumor component as well as
      whole tumor. Image noise and tumor-to-liver contrast to noise ratio during
      arterial and portal venous phases were evaluated. RESULTS: A 38% reduction in
      contrast medium dose (360.1 +/- 13.3 mgI/kg vs 583.5 +/- 21.5 mgI/kg, P < 0.001)
      and a 73% decrease in radiation dose (1898.5 mGy * cm vs 6951.8 mGy * cm) were
      observed. Interestingly, there was a strong positive correlation in hepatic
      arterial perfusion (r = 0.907, P < 0.001; r = 0.879, P < 0.001), hepatic portal
      perfusion (r = 0.819, P = 0.002; r = 0.831, P = 0.002), and hepatic blood flow (r
      = 0.945, P < 0.001; r = 0.930, P < 0.001) as well as a moderate correlation in
      hepatic perfusion index (r = 0.736, P = 0.01; r = 0.636, P = 0.035) between the
      low dose protocol with iterative reconstruction and the conventional protocol for
      the viable tumor component and the whole tumor. These two imaging protocols
      provided a moderate but acceptable agreement for perfusion parameters and similar
      tumor-to-liver CNR during arterial and portal venous phases (5.63 +/- 2.38 vs
      6.16 +/- 2.60, P = 0.814; 4.60 +/- 1.27 vs 5.11 +/- 1.74, P = 0.587). CONCLUSION:
      Compared with the conventional protocol, low contrast medium and radiation dose
      with iterative reconstruction has no significant influence on hepatic perfusion
      parameters for rabbits VX2 tumor.

PMID- 25954100
TI  - Glycyrrhizic acid inhibits apoptosis and fibrosis in carbon-tetrachloride-induced
      rat liver injury.
AB  - AIM: To investigate anti-apoptotic effects of glycyrrhizic acid (GA) against
      fibrosis in carbon tetrachloride (CCl4)-induced liver injury and its contributing
      factors. METHODS: Liver fibrosis was induced by administration of CCl4 for 8 wk.
      Pathological changes in the liver of rats were examined by hematoxylin-eosin
      staining. Collagen fibers were detected by Sirius red staining. Hepatocyte
      apoptosis was determined by TUNEL assay and the expression levels of cleaved
      caspase-3, Bax, alpha-SMA, connective tissue growth factor (CTGF), matrix
      metalloproteinase (MMP) 2 and MMP9 proteins were evaluated by western blot
      analysis, and alpha-SMA mRNA, collagen type I and III mRNA were estimated by real
      time PCR. RESULTS: Treatment with GA significantly improved the pathological
      changes in the liver and markedly decreased the positive area of Sirius red
      compared with rats in the CCl4-treated group. TUNEL assay showed that GA
      significantly reduced the number of TUNEL-positive cells compared with the CCl4
      treated group. The expression levels of cleaved caspase-3, Bax, alpha-SMA, CTGF,
      MMP2 and MMP9 proteins, and alpha-SMA mRNA, collagen type I and III mRNA were
      also significantly reduced by GA compared with the CCl4-treated group (P < 0.05).
      CONCLUSION: GA treatment can ameliorate CCl4-induced liver fibrosis by inhibiting
      hepatocyte apoptosis and hepatic stellate cell activation.

PMID- 25954101
TI  - Suitable closure for post-duodenal endoscopic resection taking medical costs into
      consideration.
AB  - AIM: To compare closure methods, closure times and medical costs between two
      groups of patients who had post-endoscopic resection (ER) artificial ulcer floor
      closures. METHODS: Nineteen patients with duodenal adenoma, early duodenal
      cancer, and subepithelial tumors that received ER between September 2009 and
      September 2014 at Kagawa University Hospital and Ehime Rosai Hospital, an
      affiliated hospital of Kagawa University, were included in the study. We
      retrospectively compared two groups of patients who received post-ER artificial
      ulcer floor closure: the conventional clip group vs the over-the-scope clip
      (OTSC) group. Delayed bleeding, procedure time of closure, delayed perforation,
      total number of conventional clips and OTSCs and medical costs were analyzed.
      RESULTS: Although we observed delayed bleeding in three patients in the
      conventional clip group, we observed no delayed bleeding in the OTSC group (P =
      0.049). We did not observe perforation in either group. The mean procedure times
      for ulcer closure were 33.26 +/- 12.57 min and 9.71 +/- 2.92 min, respectively (P
      = 0.0001). The resection diameters were 18.8 +/- 1.30 mm and 22.9 +/- 1.21 mm for
      the conventional clip group and the OTSC group, respectively, with significant
      difference (P = 0.039). As for medical costs, the costs of all conventional clips
      were USD $1257 and the costs of OTSCs were $7850 (P = 0.005). If the post-ER
      ulcer is under 20 mm in diameter, a conventional clip closure may be more
      suitable with regard to the prevention of delayed perforation and to medical
      costs. CONCLUSION: If the post-ER ulcer is over 20 mm, the OTSC closure should be
      selected with regard to safety and reliable closure even if there are high
      medical costs.

PMID- 25954102
TI  - Radiofrequency ablation for single hepatocellular carcinoma 3 cm or less as first
      line treatment.
AB  - AIM: To evaluate long-term outcomes of radiofrequency (RF) ablation as first-line
      therapy for single hepatocellular carcinoma (HCC) <= 3 cm and to determine
      survival and prognostic factors. METHODS: We included all 184 patients who
      underwent RF ablation as a first-line treatment for single HCC <= 3 cm between
      April 2005 and December 2013. According to the criteria of Livraghi, the 184
      patients were divided into two groups: those suitable for surgical resection (84
      cases) and those unsuitable for surgical resection (100 cases). The primary
      endpoints were the overall survival (OS) rate and safety; the secondary endpoints
      were primary technique effectiveness and recurrence rate. RESULTS: There were 19
      (10.3%) cases of ablation related minor complications. The complete tumor
      ablation rate after one RF session was 97.8% (180/184). The rate of local tumor
      progression, extrahepatic metastases and intrahepatic distant recurrence were
      4.9% (9/184), 9.8% (18/184) and 37.5% (69/184), respectively. In the 184
      patients, the 1-, 3-, and 5-year OS rates were 99.5%, 81.0%, and 62.5%,
      respectively. The 1-, 3-, and 5-year OS rates were 100%, 86.9%, and 71.4%,
      respectively, in those suitable for surgical resection and 99.0%, 76.0%, and
      55.0%, respectively, in those unsuitable for surgical resection (P = 0.021). On
      univariate and multivariate analyses, poorer OS was associated with Child-Pugh B
      class and portal hypertension (P < 0.05). CONCLUSION: RF ablation is a safe and
      effective treatment for single HCC <= 3 cm. The OS rate of patients suitable for
      surgical resection was similar to those reported in surgical series.

PMID- 25954103
TI  - Acute gastroenteritis outbreak caused by a GII.6 norovirus.
AB  - AIM: To report an acute gastroenteritis outbreak caused by a genogroup 2 genotype
      6 (GII.6) strain norovirus in Shanghai, China. METHODS: Noroviruses are
      responsible for approximately half of all reported gastroenteritis outbreaks in
      many countries. Genogroup 2 genotype 4 strains are the most prevalent. Rare
      outbreaks caused by GII.6 strains have been reported. An acute gastroenteritis
      outbreak occurred in an elementary school in Shanghai in December of 2013. Field
      and molecular epidemiologic investigations were conducted. RESULTS: The outbreak
      was limited to one class in an elementary school located in southwest Shanghai.
      The age of the students ranged from 9 to 10 years. The first case emerged on
      December 10, 2013, and the last case emerged on December 14, 2013. The cases
      peaked on December 11, 2013, with 21 new cases. Of 45 students in the class, 32
      were affected. The main symptom was gastroenteritis, and 15.6% (5/32) of the
      cases exhibited a fever. A field epidemiologic investigation showed the pathogen
      may have been transmitted to the elementary school from employees in a
      delicatessen via the first case student, who had eaten food from the delicatessen
      one day before the gastroenteritis episodes began. A molecular epidemiologic
      investigation identified the cause of the gastroenteritis as norovirus strain
      GII.6; the viral sequence of the student cases showed 100% homology with that of
      the shop employees. Genetic relatedness analyses showed that the new viral strain
      is closely related to previously reported GII.6 sequences, especially to a strain
      reported in Japan. CONCLUSION: This is the first report to show that norovirus
      strain GII.6 can cause a gastroenteritis outbreak. Thus, the prevalence of GII.6
      noroviruses requires attention.

PMID- 25954105
TI  - Outcome and costs of laparoscopic pancreaticoduodenectomy during the initial
      learning curve vs laparotomy.
AB  - AIM: To compare laparoscopic pancreaticoduodenectomy (TLPD) during the initial
      learning curve with open pancreaticoduodenectomy in terms of outcome and costs.
      METHODS: This is a retrospective review of the consecutive patients who underwent
      TLPD between December 2009 and April 2014 at our institution. The experiences of
      the initial 15 consecutive TLPD cases, considered as the initial learning curve
      of each surgeon, were compared with the same number of consecutive laparotomy
      cases with the same spectrum of diseases in terms of outcome and costs.
      Laparoscopic patients with conversion to open surgery were excluded. Preoperative
      demographic and comorbidity data were obtained. Postoperative data on intestinal
      movement, pain score, mortality, complications, and costs were obtained for
      analysis. Complications related to surgery included pneumonia, intra-abdominal
      abscess, postpancreatectomy hemorrhage, biliary leak, pancreatic fistula, delayed
      gastric emptying, and multiple organ dysfunction syndrome. The total costs
      consisted of cost of surgery, anesthesia, and admission examination. RESULTS: A
      total of 60 patients, including 30 consecutive laparoscopic cases and 30
      consecutive open cases, were enrolled for review. Demographic and comorbidity
      characteristics of the two groups were similar. TLPD required a significantly
      longer operative time (513.17 +/- 56.13 min vs 371.67 +/- 85.53 min, P < 0.001).
      The TLPD group had significantly fewer mean numbers of days until bowel sounds
      returned (2.03 +/- 0.55 d vs 3.83 +/- 0.59 d, P < 0.001) and exhaustion (4.17 +/-
      0.75 d vs 5.37 +/- 0.81 d, P < 0.001). The mean visual analogue score on
      postoperative day 4 was less in the TLPD group (3.5 +/- 9.7 vs 4.47 +/- 1.11, P <
      0.05). No differences in surgery-related morbidities and mortality were observed
      between the two groups. Patients in the TLPD group recovered more quickly and
      required a shorter hospital stay after surgery (9.97 +/- 3.74 d vs 11.87 +/- 4.72
      d, P < 0.05). A significant difference in the total cost was found between the
      two groups (TLPD 81317.43 +/- 2027.60 RMB vs laparotomy 78433.23 +/- 5788.12 RMB,
      P < 0.05). TLPD had a statistically higher cost for both surgery (24732.13 +/-
      929.28 RMB vs 19317.53 +/- 795.94 RMB, P < 0.001) and anesthesia (6192.37 +/-
      272.77 RMB vs 5184.10 +/- 146.93 RMB, P < 0.001), but a reduced cost for
      admission examination (50392.93 +/- 1761.22 RMB vs 53931.60 +/- 5556.94 RMB, P <
      0.05). CONCLUSION: TLPD is safe when performed by experienced pancreatobiliary
      surgeons during the initial learning curve, but has a higher cost than open
      pancreaticoduodenectomy.

PMID- 25954104
TI  - Prognostic significance of preoperative platelet count in patients with
      gallbladder cancer.
AB  - AIM: To investigate the prognostic value of preoperative platelet count (PLT) in
      patients with primary gallbladder cancer (GBC). METHODS: The clinical data of 223
      GBC patients after surgery was retrospectively reviewed. A receiver operating
      characteristic (ROC) curve was plotted to verify the optimum cutoff point for
      PLT. Univariate and multivariate survival analyses were performed to identify the
      factors associated with the prognosis. RESULTS: The ROC curve showed that the
      optimum cutoff point for PLT was 178 * 10(9)/L, and the entire cohort was
      stratified into group A with PLT > 178 * 10(9)/L and group B with PLT <= 178 *
      10(9)/L. Group A had a better survival than group B (P < 0.001). There was an
      obvious difference between the two groups in terms of the differentiation degree,
      advanced tumor stage, lymph node metastasis (P < 0.001) and pathological type (P
      < 0.05). The univariate analysis demonstrated that tumor location,
      differentiation degree, TNM stage, Nevin stage, lymph node metastasis and PLT
      were associated with overall survival (P < 0.001). In the multivariate analysis,
      PLT (P = 0.032), lymph node metastasis (P = 0.007), tumor location (P < 0.001)
      and TNM stage (P = 0.005) were independent prognostic factors. CONCLUSION: PLT is
      closely correlated with GBC prognosis and could be used to identify the
      population with a poorer prognosis after surgery.

PMID- 25954106
TI  - Metabolic syndrome and colorectal neoplasms: An ominous association.
AB  - AIM: To evaluate the association of metabolic syndrome (MS) and colorectal cancer
      and adenomas in a Western country, where the incidence of MS is over 27%.
      METHODS: This was a prospective study between March 2013 and March 2014. MS was
      diagnosed according to the National Cholesterol Education Program-ATP III.
      Demographic characteristics, anthropometric measurements, metabolic risk factors,
      and colonoscopic pathologic findings were assessed in patients with MS (group 1)
      who underwent routine colonoscopy at our department. This data was compared with
      consecutive patients without metabolic syndrome (group 2), with no differences
      regarding sex and age. Patients with incomplete colonoscopy, family history, or
      past history of colorectal neoplasm were excluded. Informed consent was obtained
      and the ethics committee approved this study. Statistical analysis was performed
      using Student's t-test and chi(2) test, with a P value <= 0.05 being considered
      statistically significant. RESULTS: Of 258 patients, 129 had MS; 51% males; mean
      age 67.1 years (50-87). Among the MS group, 94% had high blood pressure, 91% had
      increased waist circumference, 60% had diabetes, 55% had low high-density
      lipoprotein cholesterol level, 50% had increased triglyceride level, and 54% were
      obese [body mass index (BMI) 30 kg/m(2)]. 51% presented 4 criteria of MS. MS was
      associated with increased prevalence of adenomas (43% vs 25%, P = 0.004) and
      colorectal cancer (13% vs 5%, P = 0.027), compared with patients without MS. MS
      was also positively associated with multiple (>= 3) adenomas (35% vs 9%, P =
      0.024) and sessile adenomas (69% vs 53%, P = 0.05). No difference existed between
      location (P = 0.086), grade of dysplasia (P = 0.196), or size (P = 0.841) of
      adenomas. In addition, no difference was found between BMI (P = 0.078), smoking
      (P = 0.146), alcohol consumption (P = 0.231), and the presence of adenomas.
      CONCLUSION: MS is positively associated with adenomas and colorectal cancer.
      However, there is not enough information in western European countries to justify
      screening in patients with MS. To our knowledge, no previous study has evaluated
      this association in Portuguese patients.

PMID- 25954107
TI  - Improved specimen adequacy using jumbo biopsy forceps in patients with Barrett's
      esophagus.
AB  - AIM: To assess the sampling quality of four different forceps (three large
      capacity and one jumbo) in patients with Barrett's esophagus. METHODS: This was a
      prospective, single-blind study. A total of 37 patients with Barrett's esophagus
      were enrolled. Targeted or random biopsies with all four forceps were obtained
      from each patient using a diagnostic endoscope during a single endoscopy. The
      following forceps were tested: A: FB-220K disposable large capacity; B: BI01-D3
      23 reusable large capacity; C: GBF-02-23-180 disposable large capacity; and
      jumbo: disposable Radial Jaw 4 jumbo. The primary outcome measurement was
      specimen adequacy, defined as a well-oriented biopsy sample 2 mm or greater with
      the presence of muscularis mucosa. RESULTS: A total of 436 biopsy samples were
      analyzed. We found a significantly higher proportion of adequate biopsy samples
      with jumbo forceps (71%) (P < 0.001 vs forceps A: 26%, forceps B: 17%, and
      forceps C: 18%). Biopsies with jumbo forceps had the largest diameter (median 2.4
      mm) (P < 0.001 vs forceps A: 2 mm, forceps B: 1.6 mm, and forceps C: 2mm). There
      was a trend for higher diagnostic yield per biopsy with jumbo forceps (forceps A:
      0.20, forceps B: 0.22, forceps C: 0.27, and jumbo: 0.28). No complications
      related to specimen sampling were observed with any of the four tested forceps.
      CONCLUSION: Jumbo biopsy forceps, when used with a diagnostic endoscope, provide
      more adequate specimens as compared to large-capacity forceps in patients with
      Barrett's esophagus.

PMID- 25954108
TI  - Expression of pyruvate dehydrogenase is an independent prognostic marker in
      gastric cancer.
AB  - AIM: To investigate the expression and prognostic role of pyruvate dehydrogenase
      (PDH) in gastric cancer (GC). METHODS: This study included 265 patients (194
      male, 71 female, mean age 59 years (range, 29-81 years) with GC who underwent
      curative surgery at the First Affiliated Hospital of China Medical University
      from January 2006 to May 2007. All patients were followed up for more than 5
      years. Patient-derived paraffin embedded GC specimens were collected for tissue
      microarrays (TMAs). We examined PDH expression by immunohistochemistry in TMAs
      containing tumor tissue and matched non-neoplastic mucosa. Immunoreactivity was
      evaluated independently by two researchers. Overall survival (OS) rates were
      determined using the Kaplan-Meier estimator. Correlations with other
      clinicopathologic factors were evaluated by two-tailed chi(2) tests or a two
      tailed t-test. The Cox proportional-hazard model was used in univariate analysis
      and multivariate analysis to identify factors significantly correlated with
      prognosis. RESULTS: Immunohistochemistry showed that 35.47% of total cancer
      tissue specimens had cytoplasmic PDH staining. PDH expression was much higher in
      normal mucosa specimens (75.09%; P = 0.001). PDH expression was correlated with
      Lauren grade (70.77% in intestinal type vs 40.0% in diffuse type; P = 0.001),
      lymph node metastasis (65.43% with no metastasis vs 51.09% with metastasis; P =
      0.033), lymphatic invasion (61.62% with no invasion vs 38.81% with invasion; P =
      0.002), histologic subtypes (70.77% in intestinal type vs 40.0% in diffuse type;
      P = 0.001) and tumor-node-metastasis (TNM) stage (39% in poorly differentiated vs
      65.91% in well differentiated and 67.11% in moderately differentiated; P = 0.001)
      in GC. PDH expression in cancer tissue was significantly associated with higher
      OS (P < 0.001). The multivariate analysis adjusted for age, Lauren
      classification, TNM stage, lymph node metastasis, histological type, tumor size,
      depth of invasion and lymphatic invasion showed that the PDH expression in GC was
      an independent prognostic factor for higher OS (HR = 0.608, 95%CI: 0.504-0.734, P
      < 0.001). CONCLUSION: Our study indicated that PDH expression is an independent
      prognostic factor in GC patients and that positive expression of PDH may be
      predictive of favorable outcomes.

PMID- 25954109
TI  - Assessment of radiofrequency ablation margin by MRI-MRI image fusion in
      hepatocellular carcinoma.
AB  - AIM: To investigate the feasibility and clinical value of magnetic resonance
      imaging (MRI)-MRI image fusion in assessing the ablative margin (AM) for
      hepatocellular carcinoma (HCC). METHODS: A newly developed ultrasound workstation
      for MRI-MRI image fusion was used to evaluate the AM of 62 tumors in 52 HCC
      patients after radiofrequency ablation (RFA). The lesions were divided into two
      groups: group A, in which the tumor was completely ablated and 5 mm AM was
      achieved (n = 32); and group B, in which the tumor was completely ablated but 5
      mm AM was not achieved (n = 29). To detect local tumor progression (LTP), all
      patients were followed every two months by contrast-enhanced ultrasound, contrast
      enhanced MRI or computed tomography (CT) in the first year after RFA. Then, the
      follow-up interval was prolonged to every three months after the first year.
      RESULTS: Of the 62 tumors, MRI-MRI image fusion was successful in 61 (98.4%); the
      remaining case had significant deformation of the liver and massive ascites after
      RFA. The time required for creating image fusion and AM evaluation was 15.5 +/-
      5.5 min (range: 8-22 min) and 9.6 +/- 3.2 min (range: 6-14 min), respectively.
      The follow-up period ranged from 1-23 mo (14.2 +/- 5.4 mo). In group A, no LTP
      was detected in 32 lesions, whereas in group B, LTP was detected in 4 of 29
      tumors, which occurred at 2, 7, 9, and 15 mo after RFA. The frequency of LTP in
      group B (13.8%; 4/29) was significantly higher than that in group A (0/32, P =
      0.046). All of the LTPs occurred in the area in which the 5 mm AM was not
      achieved. CONCLUSION: The MRI-MRI image fusion using an ultrasound workstation is
      feasible and useful for evaluating the AM after RFA for HCC.

PMID- 25954110
TI  - Gastrointestinal perforation in metastatic colorectal cancer patients with
      peritoneal metastases receiving bevacizumab.
AB  - AIM: To investigate the safety and efficacy of adding bevacizumab to first-line
      chemotherapy in metastatic colorectal cancer patients with peritoneal disease.
      METHODS: We compared rates of gastrointestinal perforation in patients with
      metastatic colorectal cancer and peritoneal disease receiving first-line
      chemotherapy with and without bevacizumab in three distinct cohorts: (1) the
      AGITG MAX trial (Phase III randomised clinical trial comparing capecitabine vs
      capecitabine and bevacizumab vs capecitabine, bevacizumab and mitomycinC); (2)
      the prospective Treatment of Recurrent and Advanced Colorectal Cancer (TRACC)
      registry (any first-line regimen +/- bevacizumab); and (3) two cancer centres in
      New South Wales, Australia [Macarthur Cancer Therapy Centre and Liverpool Cancer
      Therapy Centre (NSWCC) from January 2005 to Decenber 2012, (any first-line
      regimen +/- bevacizumab). For the AGITG MAX trial capecitabine was compared to
      the other two arms (capecitabine/bevacizumab and
      capecitabine/bevacizumab/mitomycinC). In the AGITG MAX trial and the TRACC
      registry rates of gastrointestinal perforation were also collected in patients
      who did not have peritoneal metastases. Secondary endpoints included progression
      free survival, chemotherapy duration, and overall survival. Time-to-event
      outcomes were estimated using the Kaplan-Meier method and compared using the log
      rank test. RESULTS: Eighty-four MAX, 179 TRACC and 69 NSWCC patients had
      peritoneal disease. There were no gastrointestinal perforations recorded in
      either the MAX subgroup or the NSWCC cohorts. Of the patients without peritoneal
      disease in the MAX trial, 4/300 (1.3%) in the bevacizumab arms had
      gastrointestinal perforations compared to 1/123 (0.8%) in the capecitabine alone
      arm. In the TRACC registry 3/126 (2.4%) patients who had received bevacizumab had
      a gastrointestinal perforation compared to 1/53 (1.9%) in the chemotherapy alone
      arm. In a further analysis of patients without peritoneal metastases in the TRACC
      registry, the rate of gastrointestinal perforations was 9/369 (2.4%) in the
      chemotherapy/bevacizumab group and 5/177 (2.8%) in the chemotherapy alone group.
      The addition of bevacizumab to chemotherapy was associated with improved
      progression-free survival in all three cohorts: MAX 6.9 m vs 4.9 m, HR = 0.64
      (95%CI: 0.42-1.02); P = 0.063; TRACC 9.1 m vs 5.5 m, HR = 0.61 (95%CI: 0.37
      0.86); P = 0.009; NSWCC 8.7 m vs 6.8 m, HR = 0.75 (95%CI: 0.43-1.32); P = 0.32.
      Chemotherapy duration was similar across the groups. CONCLUSION: Patients with
      peritoneal disease do not appear to have an increased risk of gastrointestinal
      perforations when receiving first-line therapy with bevacizumab compared to
      systemic therapy alone.

PMID- 25954111
TI  - Fecal microbiota transplantation as novel therapy in gastroenterology: A
      systematic review.
AB  - AIM: To study the clinical efficacy and safety of Fecal microbiota
      transplantation (FMT). We systematically reviewed FMT used as clinical therapy.
      METHODS: We searched MEDLINE, EMBASE, the Cochrane Library and Conference
      proceedings from inception to July, 2013. Treatment effect of FMT was calculated
      as the percentage of patients who achieved clinical improvement per patient
      category, on an intention-to-treat basis. RESULTS: We included 45 studies; 34 on
      Clostridium difficile-infection (CDI), 7 on inflammatory bowel disease, 1 on
      metabolic syndrome, 1 on constipation, 1 on pouchitis and 1 on irritable bowel
      syndrome (IBS). In CDI 90% resolution of diarrhea in 33 case series (n = 867) was
      reported, and 94% resolution of diarrhea after repeated FMT in a randomized
      controlled trial (RCT) (n = 16). In ulcerative colitis (UC) remission rates of 0%
      to 68% were found (n = 106). In Crohn's disease (CD) (n = 6), no benefit was
      observed. In IBS, 70% improvement of symptoms was found (n = 13). 100% Reversal
      of symptoms was observed in constipation (n = 3). In pouchitis, none of the
      patients (n = 8) achieved remission. One RCT showed significant improvement of
      insulin sensitivity in metabolic syndrome (n = 10). Serious adverse events were
      rare. CONCLUSION: FMT is highly effective in CDI, and holds promise in UC. As for
      CD, chronic constipation, pouchitis and IBS data are too limited to draw
      conclusions. FMT increases insulin sensitivity in metabolic syndrome.

PMID- 25954112
TI  - Fiber and prebiotic supplementation in enteral nutrition: A systematic review and
      meta-analysis.
AB  - AIM: To investigate fiber and prebiotic supplementation of enteral nutrition (EN)
      for diarrhea, fecal microbiota and short-chain fatty acids (SCFAs). METHODS:
      MEDLINE, EMBASE, Cochrane Library, CINAHL, Academic Search Premier, and Web of
      Science databases were searched for human experimental and observational cohort
      studies conducted between January 1990 and June 2014. The keywords used for the
      literature search were fiber, prebiotics and enteral nutrition. English language
      studies with adult patient populations on exclusive EN were selected. Abstracts
      and/or full texts of selected studies were reviewed and agreed upon by two
      independent researchers for inclusion in the meta-analysis. Tools used for the
      quality assessment were Jadad Scale and the Scottish Intercollegiate Guidelines
      Network Critical Appraisal of the Medical Literature. RESULTS: A total of 456
      possible articles were retrieved, and 430 were excluded due to lack of
      appropriate data. Of the 26 remaining studies, only eight investigated the
      effects of prebiotics. Results of the meta-analysis indicated that overall, fiber
      reduces diarrhea in patients receiving EN (OR = 0.47; 95%CI: 0.29-0.77; P =
      0.02). Subgroup analysis revealed a positive effect of fiber supplementation in
      EN towards diarrhea in stable patients (OR = 0.31; 95%CI: 0.19-0.51; P < 0.01),
      but not in critically ill patients (OR = 0.89; 95%CI: 0.41-1.92; P = 0.77).
      Prebiotic supplementation in EN does not improve the incidence of diarrhea
      despite its manipulative effect on bifidobacteria concentrations and SCFA in
      healthy humans. In addition, the effect of fiber and/or prebiotic supplementation
      towards fecal microbiota and SCFA remain disputable. CONCLUSION: Fiber helps
      minimize diarrhea in patients receiving EN, particularly in non-critically ill
      patients. However, the effect of prebiotics in moderating diarrhea is
      inconclusive.

PMID- 25954113
TI  - Proton pump inhibitors in prevention of low-dose aspirin-associated upper
      gastrointestinal injuries.
AB  - AIM: To determine the preventive effect and safety of proton pump inhibitors
      (PPIs) in low-dose aspirin (LDA)-associated gastrointestinal (GI) ulcers and
      bleeding. METHODS: We searched MEDLINE, EMBASE and the Cochrane Controlled Trials
      Register from inception to December 2013, and checked conference abstracts of
      randomized controlled trials (RCTs) on the effect of PPIs in reducing adverse GI
      events (hemorrhage, ulcer, perforation, or obstruction) in patients taking LDA.
      The preventive effects of PPIs were compared with the control group [taking
      placebo, a cytoprotective agent, or an H2 receptor antagonist (H2RA)] in LDA
      associated upper GI injuries. The meta-analysis was performed using RevMan 5.1
      software. RESULTS: We evaluated 8780 participants in 10 RCTs. The meta-analysis
      showed that PPIs decreased the risk of LDA-associated upper GI ulcers (OR = 0.16;
      95%CI: 0.12-0.23) and bleeding (OR = 0.27; 95%CI: 0.16-0.43) compared with
      control. For patients treated with dual anti-platelet therapy of LDA and
      clopidogrel, PPIs were able to prevent the LDA-associated GI bleeding (OR = 0.36;
      95%CI: 0.15-0.87) without increasing the risk of major adverse cardiovascular
      events (MACE) (OR = 1.00; 95%CI: 0.76-1.31). PPIs were superior to H2RA in
      prevention of LDA-associated GI ulcers (OR = 0.12; 95%CI: 0.02-0.65) and bleeding
      (OR = 0.32; 95%CI: 0.13-0.79). CONCLUSION: PPIs are effective in preventing LDA
      associated upper GI ulcers and bleeding. Concomitant use of PPI, LDA and
      clopidogrel did not increase the risk of MACE.

PMID- 25954114
TI  - Transvaginal cholecystectomy vs conventional laparoscopic cholecystectomy for
      gallbladder disease: A meta-analysis.
AB  - AIM: To compare the results of transvaginal cholecystectomy (TVC) and
      conventional laparoscopic cholecystectomy (CLC) for gallbladder disease. METHODS:
      We performed a literature search of PubMed, EMBASE, Ovid, Web of Science,
      Cochrane Library, Google Scholar, MetaRegister of Controlled Trials, Chinese
      Medical Journal database and Wanfang Data for trials comparing outcomes between
      TVC and CLC. Data were extracted by two authors. Mean difference (MD),
      standardized mean difference (SMD), odds ratios and risk rate with 95%CIs were
      calculated using fixed- or random-effects models. Statistical heterogeneity was
      evaluated with the chi(2) test. The fixed-effects model was used in the absence
      of statistically significant heterogeneity. The random-effects model was chosen
      when heterogeneity was found. RESULTS: There were 730 patients in nine controlled
      clinical trials. No significant difference was found regarding demographic
      characteristics (P > 0.5), including anesthetic risk score, age, body mass index,
      and abdominal surgical history between the TVC and CLC groups. Both groups had
      similar mortality, morbidity, and return to work after surgery. Patients in the
      TVC group had a lower pain score on postoperative day 1 (SMD: -0.957, 95%CI: 
      1.488 to -0.426, P < 0.001), needed less postoperative analgesic medication (SMD:
      -0.574, 95%CI: -0.807 to -0.341, P < 0.001) and stayed for a shorter time in
      hospital (MD: -1.004 d, 95%CI: -1.779 to 0.228, P = 0.011), but had longer
      operative time (MD: 17.307 min, 95%CI: 6.789 to 27.826, P = 0.001). TVC had no
      significant influence on postoperative sexual function and quality of life.
      Better cosmetic results and satisfaction were achieved in the TVC group.
      CONCLUSION: TVC is safe and effective for gallbladder disease. However, vaginal
      injury might occur, and further trials are needed to compare TVC with CLC.

PMID- 25954115
TI  - Is Helicobacter pylori infection associated with glycemic control in diabetics?
AB  - AIM: To investigate whether Helicobacter pylori (H. pylori) infection is
      associated with glycemic control and whether hyperglycemia is modified by
      eradication therapy. METHODS: The databases of PubMed, Cochrane Library, Chinese
      BioMedicine Web Base and Chinese Science and Technology Journals were searched
      from inception to June 2014. Studies examining the association between H. pylori
      infection and glycemic control and/or the effect of eradication treatment on
      glycemic control in diabetic humans were eligible for inclusion. Meta-analyses
      were conducted using the Review Manager software version 5.2. The outcome
      measures are presented as weighed mean differences (WMDs) with 95% confidence
      intervals (CIs). Statistical heterogeneity was assessed by the Cochran Q test and
      the I(2) statistic. RESULTS: A total of 21 relevant publications were identified.
      A meta-analysis of 11 studies with 513 patients with diabetes mellitus (DM)
      showed significantly lower glycosylated hemoglobin (HbA1c) levels in the H.
      pylori-negative than H. pylori-positive DM participants (WMD = 0.43, 95%CI: 0.07
      0.79; P = 0.02). In children and adolescents with type 1 DM (T1DM), there was a
      positive association between H. pylori infection and HbA1c level (WMD = 0.35,
      95%CI: 0.05-0.64; P = 0.02), but there was no difference in those with type 2 DM
      (T2DM, WMD = 0.51, 95%CI: -0.63-1.65; P = 0.38). A meta-analysis of six studies
      with 325 T2DM participants showed a significant difference in the fasting plasma
      glucose levels between H. pylori-positive and H. pylori-negative participants
      (WMD = 1.20, 95%CI: 0.17-2.23; P = 0.02). Eradication of H. pylori did not
      improve glycemic control in the T2DM participants in a three-month follow-up
      period (HbA1c decrease: WMD = -0.03, 95%CI = -0.14-0.08; P = 0.57; fasting plasma
      glucose decrease: WMD = -0.06, 95%CI: -0.36-0.23; P = 0.68). Glycemic control was
      significantly better in T1DM participants who were not reinfected than in those
      who were reinfected (HbA1c: WMD = 0.72, 95%CI: 0.32-1.13: P = 0.00). CONCLUSION:
      H. pylori infection is associated with poorer glycemic control in T1DM patients,
      but eradication may not improve glycemic control in DM in a short-term follow-up
      period.

PMID- 25954116
TI  - Weber-Christian disease with ileocolonic involvement successfully treated with
      infliximab.
AB  - Weber-Christian disease (WCD) is an inflammatory disease whose main histological
      feature is lobular panniculitis of adipose tissue. The location of panniculitis
      determines the clinical presentation, being the subcutaneous adipose tissue the
      most frequent one, followed by liver, spleen, bone marrow and mesenteric adipose
      tissue. Systemic corticosteroids are first line treatment, but other options
      should be considered if systemic symptoms are observed or in case of refractory
      clinical situation. We report herein a case with WCD showing orbital, mesenteric
      and ileocolonic involvement, which required surgical treatment and also developed
      postoperative recurrence. Symptoms were resolved by administration of thalidomide
      and, afterwards, infliximab. To our knowledge, this is the first report of Weber
      Christian disease with luminal ileocolonic involvement, treated with infliximab. 

PMID- 25954117
TI  - Aplastic anemia and severe pancytopenia during treatment with peg-interferon,
      ribavirin and telaprevir for chronic hepatitis C.
AB  - Telaprevir and Boceprevir are the first direct acting antivirals approved for
      chronic hepatitis C in combination with peg-interferon alfa and ribavirin.
      Pancytopenia due to myelotoxicity caused by these drugs may occur, but severe
      hematological abnormalities or aplastic anemia (AA) have not been described. We
      collected all cases of severe pancytopenia observed during triple therapy with
      telaprevir in four Spanish centers since approval of the drug in 2011. Among 142
      cirrhotic patients receiving treatment, 7 cases of severe pancytopenia (5%) were
      identified and three were consistent with the diagnosis of AA. Mean age was 59
      years, five patients had compensated cirrhosis and two patients had severe
      hepatitis C recurrence after liver transplantation. Severe pancytopenia was
      diagnosed a median of 10 wk after the initiation of therapy. Three patients had
      pre-treatment hematological abnormalities related to splenomegaly. In six
      patients, antiviral treatment was interrupted at the onset of hematological
      abnormalities. Two patients died due to septic complications and one patient due
      to acute alveolar hemorrhage. The remaining patients recovered. Severe
      pancytopenia and especially AA, are not rare during triple therapy with
      telaprevir in patients with advanced liver disease. Close monitoring is
      imperative in this setting to promptly detect serious hematological disorders and
      to prevent further complications. 

PMID- 25954118
TI  - Primary retroperitoneal mucinous cystadenoma: A case report.
AB  - Primary retroperitoneal mucinous cystic tumors are extremely rare. These tumors
      can be classified as a primary retroperitoneal mucinous cystadenoma with or
      without borderline malignancy or primary retroperitoneal mucinous
      cystadenocarcinoma. The most common of these is primary retroperitoneal mucinous
      cystadenoma, which almost always occurs in female patients; only ten cases have
      been reported in males. The most common clinical findings for this tumor type
      include nonspecific abdominal pain and a palpable abdominal mass. A definitive
      diagnosis is usually obtained from histopathology after surgical excision. Here,
      we report the case of a 60-year-old female patient who complained of abdominal
      pain that had been present for 3 mo and presented with a palpable abdominal mass.
      Multidetector computed tomography scanning revealed a large, unilocular cystic
      mass in the left retroperitoneal space. Surgical intervention was performed and
      the tumor was completely removed. Histopathologic examination confirmed that the
      tumor was a primary retroperitoneal mucinous cystadenoma. Two years after
      surgery, the patient remains disease free. 

PMID- 25954120
TI  - Hemolymphangioma of the spleen: A report of a rare case.
AB  - Hemolymphangioma is a malformation of both lymphatic vessels and blood vessels.
      Splenic hemolymphangioma is extremely rare. Herein, we present a case of 62-year
      old woman with ambiguous upper quadrant abdominal pain for two months who was
      found to have an occupying lesion in the spleen on computed tomography. She was
      eventually diagnosed with hemolymphangioma of the spleen. The patient underwent
      total splenectomy. Neither symptoms nor recurrence was found during the one-year
      follow-up period. 

PMID- 25954119
TI  - Improving recognition of hepatic perivascular epithelioid cell tumor: Case report
      and literature review.
AB  - A 58-year-old man presented with the chief complaint of abdominal bloating and
      was incidentally found to have a liver tumor. As diagnostic imaging studies could
      not rule out malignancy, the patient underwent partial resection of segment 3 of
      the liver. The lesion pathologically showed eosinophilic proliferation, in
      addition to immunohistochemical positivity for human melanoma black 45 and Melan
      A, thereby leading to the diagnosis of a hepatic perivascular epithelioid cell
      tumor (PEComa). A PEComa arising from the liver is relatively rare. Moreover, the
      name 'PEComa' has not yet been widely recognized, and the same disease entity has
      been called epithelioid angiomyolipoma (EAML), further diminishing the
      recognition of PEComa. In addition, PEComa imaging findings mimic those of
      malignant liver tumors, and clinically, this tumor tends to enlarge. Therefore, a
      PEComa is difficult to diagnose. We conducted a systematic review of PEComa and
      EAML cases and discuss the results, including findings useful for differentiating
      perivascular epithelioid cell tumors from malignant liver tumors. 

PMID- 25954121
TI  - RAPID INDUCTION OF HETEROGENEOUS ICE NUCLEATION IN A BIOLOGICALLY COMPATIBLE
      COOLANT.
AB  - Hypothermia is gaining recognition as an important medical treatment. To treat
      local cases of injury such as stroke, or certain surgical procedures, there is a
      need to induce local hypothermia. To treat shock or cardiac arrest survivors,
      there is a need to rapidly induce global hypothermia. Rapid induction of
      hypothermia has been achieved in animal research, but it has yet to be achieved
      clinically using a simple, widely practicable method. The clinical need for
      therapeutic hypothermia represents an engineering opportunity to develop an easy
      to use coolant that is sterile, biologically compatible, and maximizes coolant
      heat capacity. Here we present an initial characterization of a prototype
      platform technology designed to create a sterile, biologically compatible, high
      heat capacity coolant that has the potential to be used in all of these clinical
      applications. The coolant is a specially processed micro-particulate ice saline
      slurry, that can be easily pumped into a patient through surgical tubing,
      syringes, or minimally invasive surgical instruments. The device induces
      heterogeneous ice nucleation in a saline stream that has been super-cooled from
      room temperature to a temperature below the saline freezing point. Currently, the
      device begins continuous production of ice slurry that contains ~30 % ice by mass
      within 10 minutes. The nominal ice particle diameter is smaller than 100 MUm.
      This work represents a significant first step toward addressing clinical needs
      for rapid human cooling.

PMID- 25954123
TI  - Effect of sulfonylureas administered centrally on the blood glucose level in
      immobilization stress model.
AB  - Sulfonylureas are widely used as an antidiabetic drug. In the present study, the
      effects of sulfonylurea administered supraspinally on immobilization stress
      induced blood glucose level were studied in ICR mice. Mice were once enforced
      into immobilization stress for 30 min and returned to the cage. The blood glucose
      level was measured 30, 60, and 120 min after immobilization stress initiation. We
      found that intracerebroventricular (i.c.v.) injection with 30 ug of glyburide,
      glipizide, glimepiride or tolazamide attenuated the increased blood glucose level
      induced by immobilization stress. Immobilization stress causes an elevation of
      the blood corticosterone and insulin levels. Sulfonylureas pretreated i.c.v.
      caused a further elevation of the blood corticosterone level when mice were
      forced into the stress. In addition, sulfonylureas pretreated i.c.v. alone caused
      an elevation of the plasma insulin level. Furthermore, immobilization stress
      induced insulin level was reduced by i.c.v. pretreated sulfonylureas. Our results
      suggest that lowering effect of sulfonylureas administered supraspinally against
      immobilization stress-induced increase of the blood glucose level appears to be
      primarily mediated via elevation of the plasma insulin level. 

PMID- 25954124
TI  - EGCG Blocked Phenylephrin-Induced Hypertrophy in H9C2 Cardiomyocytes, by
      Activating AMPK-Dependent Pathway.
AB  - AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism.
      Previous studies have shown that activation of AMPK results in suppression of
      cardiac myocyte hypertrophy via inhibition of the p70S6 kinase (p70S6K) and
      eukaryotic elongation factor-2 (eEF2) signaling pathways. Epigallocatechin-3
      gallate (EGCG), the major polyphenol found in green tea, possesses multiple
      protective effects on the cardiovascular system including cardiac hypertrophy.
      However, the molecular mechanisms has not been well investigated. In this study,
      we found that EGCG could significantly reduce natriuretic peptides type A (Nppa),
      brain natriuretic polypeptide (BNP) mRNA expression and decrease cell surface
      area in H9C2 cardiomyocytes stimulated with phenylephrine (PE). Moreover, we
      showed that AMPK is activated in H9C2 cardiomyocytes by EGCG, and AMPK-dependent
      pathway participates in the inhibitory effects of EGCG on cardiac hypertrophy.
      Taken together, our findings provide the first evidence that the effect of EGCG
      against cardiac hypertrophy may be attributed to its activation on AMPK-dependent
      signaling pathway, suggesting the therapeutic potential of EGCG on the prevention
      of cardiac remodeling in patients with pressure overload hypertrophy. 

PMID- 25954122
TI  - Low intensity resistance exercise training with blood flow restriction: insight
      into cardiovascular function, and skeletal muscle hypertrophy in humans.
AB  - Attenuated functional exercise capacity in elderly and diseased populations is a
      common problem, and stems primarily from physical inactivity. Decreased function
      and exercise capacity can be restored by maintaining muscular strength and mass,
      which are key factors in an independent and healthy life. Resistance exercise has
      been used to prevent muscle loss and improve muscular strength and mass. However,
      the intensities necessary for traditional resistance training to increase
      muscular strength and mass may be contraindicated for some at risk populations,
      such as diseased populations and the elderly. Therefore, an alternative exercise
      modality is required. Recently, blood flow restriction (BFR) with low intensity
      resistance exercise (LIRE) has been used for such special populations to improve
      their function and exercise capacity. Although BFR+LIRE has been intensively
      studied for a decade, a comprehensive review detailing the effects of BFR+LIRE on
      both skeletal muscle and vascular function is not available. Therefore, the
      purpose of this review is to discuss previous studies documenting the effects of
      BFR+LIRE on hormonal and transcriptional factors in muscle hypertrophy and
      vascular function, including changes in hemodynamics, and endothelial function. 

PMID- 25954125
TI  - Silymarin Inhibits Morphological Changes in LPS-Stimulated Macrophages by
      Blocking NF-kappaB Pathway.
AB  - The present study showed that silymarin, a polyphenolic flavonoid isolated from
      milk thistle (Silybum marianum), inhibited lipopolysaccharide (LPS)-induced
      morphological changes in the mouse RAW264.7 macrophage cell line. We also showed
      that silymarin inhibited the nuclear translocation and transactivation activities
      of nuclear factor-kappa B (NF-kappaB), which is important for macrophage
      activation-associated changes in cell morphology and gene expression of
      inflammatory cytokines. BAY-11-7085, an NF-kappaB inhibitor, abrogated LPS
      induced morphological changes and NO production, similar to silymarin. Treatment
      of RAW264.7 cells with silymarin also inhibited LPS-stimulated activation of
      mitogen-activated protein kinases (MAPKs). Collectively, these experiments
      demonstrated that silymarin inhibited LPS-induced morphological changes in the
      RAW264.7 mouse macrophage cell line. Our findings indicated that the most likely
      mechanism underlying this biological effect involved inhibition of the MAPK
      pathway and NF-kappaB activity. Inhibition of these activities by silymarin is a
      potentially useful strategy for the treatment of inflammation because of the
      critical roles played by MAPK and NF-kappaB in mediating inflammatory responses
      in macrophages. 

PMID- 25954126
TI  - Dieckol Attenuates Microglia-mediated Neuronal Cell Death via ERK, Akt and NADPH
      Oxidase-mediated Pathways.
AB  - Excessive microglial activation and subsequent neuroinflammation lead to synaptic
      loss and dysfunction as well as neuronal cell death, which are involved in the
      pathogenesis and progression of several neurodegenerative diseases. Thus, the
      regulation of microglial activation has been evaluated as effective therapeutic
      strategies. Although dieckol (DEK), one of the phlorotannins isolated from marine
      brown alga Ecklonia cava, has been previously reported to inhibit microglial
      activation, the molecular mechanism is still unclear. Therefore, we investigated
      here molecular mechanism of DEK via extracellular signal-regulated kinase (ERK),
      Akt and nicotinamide adenine dinuclelotide phosphate (NADPH) oxidase-mediated
      pathways. In addition, the neuroprotective mechanism of DEK was investigated in
      microglia-mediated neurotoxicity models such as neuron-microglia co-culture and
      microglial conditioned media system. Our results demonstrated that treatment of
      anti-oxidant DEK potently suppressed phosphorylation of ERK in lipopolysaccharide
      (LPS, 1 ug/ml)-stimulated BV-2 microglia. In addition, DEK markedly attenuated
      Akt phosphorylation and increased expression of gp91 (phox) , which is the
      catalytic component of NADPH oxidase complex responsible for microglial reactive
      oxygen species (ROS) generation. Finally, DEK significantly attenuated neuronal
      cell death that is induced by treatment of microglial conditioned media
      containing neurotoxic secretary molecules. These neuroprotective effects of DEK
      were also confirmed in a neuron-microglia co-culture system using enhanced green
      fluorescent protein (EGFP)-transfected B35 neuroblastoma cell line. Taken
      together, these results suggest that DEK suppresses excessive microglial
      activation and microglia-mediated neuronal cell death via downregulation of ERK,
      Akt and NADPH oxidase-mediated pathways. 

PMID- 25954127
TI  - Nafamostat Mesilate Inhibits TNF-alpha-Induced Vascular Endothelial Cell
      Dysfunction by Inhibiting Reactive Oxygen Species Production.
AB  - Nafamostat mesilate (NM) is a serine protease inhibitor with anticoagulant and
      anti-inflammatory effects. NM has been used in Asia for anticoagulation during
      extracorporeal circulation in patients undergoing continuous renal replacement
      therapy and extra corporeal membrane oxygenation. Oxidative stress is an
      independent risk factor for atherosclerotic vascular disease and is associated
      with vascular endothelial function. We investigated whether NM could inhibit
      endothelial dysfunction induced by tumor necrosis factor-alpha (TNF-alpha). Human
      umbilical vein endothelial cells (HUVECs) were treated with TNF-alpha for 24 h.
      The effects of NM on monocyte adhesion, vascular cell adhesion molecule-1 (VCAM
      1) and intracellular adhesion molecule-1 (ICAM-1) protein expression, p38 mitogen
      activated protein kinase (MAPK) activation, and intracellular superoxide
      production were then examined. NM (0.01~100 ug/mL) did not affect HUVEC
      viability; however, it inhibited the increases in reactive oxygen species (ROS)
      production and p66shc expression elicited by TNF-alpha (3 ng/mL), and it dose
      dependently prevented the TNF-alpha-induced upregulation of endothelial VCAM-1
      and ICAM-1. In addition, it mitigated TNF-alpha-induced p38 MAPK phosphorylation
      and the adhesion of U937 monocytes. These data suggest that NM mitigates TNF
      alpha-induced monocyte adhesion and the expression of endothelial cell adhesion
      molecules, and that the anti-adhesive effect of NM is mediated through the
      inhibition of p66shc, ROS production, and p38 MAPK activation. 

PMID- 25954128
TI  - Androgen Receptor-dependent Expression of Low-density Lipoprotein Receptor
      related Protein 6 is Necessary for Prostate Cancer Cell Proliferation.
AB  - Androgen receptor (AR) signaling is important for prostate cancer (PCa) cell
      proliferation. Here, we showed that proliferation of hormone-sensitive prostate
      cancer cells such as LNCaP was significantly enhanced by testosterone stimulation
      whereas hormone-insensitive prostate cancer cells such as PC3 and VCaP did not
      respond to testosterone stimulation. Blocking of AR using bicalutamide abolished
      testosterone-induced proliferation of LNCaP cells. In addition, knockdown of AR
      blocked testosterone-induced proliferation of LNCaP cells. Basal expression of
      low-density lipoprotein receptor-related protein 6 (LRP6) was elevated in VCaP
      cells whereas stimulation of testosterone did not affect the expression of LRP6.
      However, expression of LRP6 in LNCaP cells was increased by testosterone
      stimulation. In addition, knockdown of LRP6 abrogated testosterone-induced
      proliferation of LNCaP cells. Given these results, we suggest that androgen
      dependent expression of LRP6 plays a crucial role in hormone-sensitive prostate
      cancer cell proliferation. 

PMID- 25954129
TI  - p-Coumaric Acid Attenuates UVB-Induced Release of Stratifin from Keratinocytes
      and Indirectly Regulates Matrix Metalloproteinase 1 Release from Fibroblasts.
AB  - Ultraviolet (UV) radiation-induced loss of dermal extracellular matrix is
      associated with skin photoaging. Recent studies demonstrated that keratinocyte
      releasable stratifin (SFN) plays a critical role in skin collagen metabolism by
      inducing matrix metalloproteinase 1 (MMP1) expression in target fibroblasts. In
      the present study, we examined whether SFN released from UVB-irradiated epidermal
      keratinocytes increases MMP1 release from dermal fibroblasts, and whether these
      events are affected by p-coumaric acid (p-CA), a natural phenolic compound with
      UVB-shielding and antioxidant properties. HaCaT cells were exposed to UVB in the
      absence and presence of p-CA, and the conditioned medium was used to stimulate
      fibroblasts in medium transfer experiments. The cells and media were analyzed to
      determine the expressions/releases of SFN and MMP1. UVB exposure increased SFN
      release from keratinocytes into the medium. The conditioned medium of UVB
      irradiated keratinocytes increased MMP1 release from fibroblasts. The depletion
      of SFN using a siRNA rendered the conditioned medium of UVB-irradiated
      keratinocytes ineffective at stimulating fibroblasts to release MMP1. p-CA
      mitigated UVB-induced SFN expression in keratinocytes, and attenuated the MMP1
      release by fibroblasts in medium transfer experiments. In conclusion, the present
      study demonstrated that the use of UV absorbers such as p-CA would reduce UV
      induced SFN-centered signaling events involved in skin photoaging. 

PMID- 25954130
TI  - Ca(2+) is a Regulator of the WNK/OSR1/NKCC Pathway in a Human Salivary Gland Cell
      Line.
AB  - Wnk kinase maintains cell volume, regulating various transporters such as sodium
      chloride cotransporter, potassium-chloride cotransporter, and sodium-potassium
      chloride cotransporter 1 (NKCC1) through the phosphorylation of oxidative stress
      responsive kinase 1 (OSR1) and STE20/SPS1-related proline/alanine-rich kinase
      (SPAK). However, the activating mechanism of Wnk kinase in specific tissues and
      specific conditions is broadly unclear. In the present study, we used a human
      salivary gland (HSG) cell line as a model and showed that Ca(2+) may have a role
      in regulating Wnk kinase in the HSG cell line. Through this study, we found that
      the HSG cell line expressed molecules participating in the WNK-OSR1-NKCC pathway,
      such as Wnk1, Wnk4, OSR1, SPAK, and NKCC1. The HSG cell line showed an
      intracellular Ca(2+) concentration ([Ca(2+)]i) increase in response to hypotonic
      stimulation, and the response was synchronized with the phosphorylation of OSR1.
      Interestingly, when we inhibited the hypotonically induced [Ca(2+)]i increase
      with nonspecific Ca(2+) channel blockers such as 2-aminoethoxydiphenyl borate,
      gadolinium, and lanthanum, the phosphorylated OSR1 level was also diminished.
      Moreover, a cyclopiazonic acid-induced passive [Ca(2+)]i elevation was evoked by
      the phosphorylation of OSR1, and the amount of phosphorylated OSR1 decreased when
      the cells were treated with BAPTA, a Ca(2+) chelator. Finally, through that
      process, NKCC1 activity also decreased to maintain the cell volume in the HSG
      cell line. These results indicate that Ca(2+) may regulate the WNK-OSR1 pathway
      and NKCC1 activity in the HSG cell line. This is the first demonstration that
      indicates upstream Ca(2+) regulation of the WNK-OSR1 pathway in intact cells. 

PMID- 25954131
TI  - Nicotine in high concentration causes contraction of isolated strips of rabbit
      corpus cavernosum.
AB  - It is well known that cigarette smoke can cause erectile dysfunction by affecting
      the penile vascular system. However, the exact effects of nicotine on the corpus
      cavernosum remains poorly understood. Nicotine has been reported to cause
      relaxation of the corpus cavernosum; it has also been reported to cause both
      contraction and relaxation. Therefore, high concentrations of nicotine were
      studied in strips from the rabbit corpus cavernosum to better understand its
      effects. The proximal penile corpus cavernosal strips from male rabbits weighing
      approximately 4 kg were used in organ bath studies. Nicotine in high
      concentrations (10(-5)~10(-4) M) produced dose-dependent contractions of the
      corpus cavernosal strips. The incubation with 10(-5) M hexamethonium (nicotinic
      receptor antagonist) significantly inhibited the magnitude of the nicotine
      associated contractions. The nicotine-induced contractions were not only
      significantly inhibited by pretreatment with 10(-5) M indomethacin (nonspecific
      cyclooxygenase inhibitor) and with 10(-6) M NS-398 (selective cyclooxygenase
      inhibitor), but also with 10(-6) M Y-27632 (Rho kinase inhibitor). Ozagrel
      (thromboxane A2 synthase inhibitor) and SQ-29548 (highly selective TP receptor
      antagonist) pretreatments significantly reduced the nicotine-induced contractile
      amplitude of the strips. High concentrations of nicotine caused contraction of
      isolated rabbit corpus cavernosal strips. This contraction appeared to be
      mediated by activation of nicotinic receptors. Rho-kinase and cyclooxygenase
      pathways, especially cyclooxygenase-2 and thromboxane A2, might play a pivotal
      role in the mechanism associated with nicotine-induced contraction of the rabbit
      corpus cavernosum. 

PMID- 25954132
TI  - LPS Increases 5-LO Expression on Monocytes via an Activation of Akt-Sp1/NF-kappaB
      Pathways.
AB  - 5-Lipoxygenase (5-LO) plays a pivotal role in the progression of atherosclerosis.
      Therefore, this study investigated the molecular mechanisms involved in 5-LO
      expression on monocytes induced by LPS. Stimulation of THP-1 monocytes with LPS
      (0~3 ug/ml) increased 5-LO promoter activity and 5-LO protein expression in a
      concentration-dependent manner. LPS-induced 5-LO expression was blocked by
      pharmacological inhibition of the Akt pathway, but not by inhibitors of MAPK
      pathways including the ERK, JNK, and p38 MAPK pathways. In line with these
      results, LPS increased the phosphorylation of Akt, suggesting a role for the Akt
      pathway in LPS-induced 5-LO expression. In a promoter activity assay conducted to
      identify transcription factors, both Sp1 and NF-kappaB were found to play central
      roles in 5-LO expression in LPS-treated monocytes. The LPS-enhanced activities of
      Sp1 and NF-kappaB were attenuated by an Akt inhibitor. Moreover, the LPS-enhanced
      phosphorylation of Akt was significantly attenuated in cells pretreated with an
      anti-TLR4 antibody. Taken together, 5-LO expression in LPS-stimulated monocytes
      is regulated at the transcriptional level via TLR4/Akt-mediated activations of
      Sp1 and NF-kappaB pathways in monocytes. 

PMID- 25954133
TI  - Short-term Treatment of Daumone Improves Hepatic Inflammation in Aged Mice.
AB  - Chronic inflammation has been proposed as one of the main molecular mechanisms of
      aging and age-related diseases. Although evidence in humans is limited, short
      term calorie restriction (CR) has been shown to have anti-inflammatory effects in
      aged experimental animals. We reported on the long-term treatment of daumone, a
      synthetic pheromone secreted by Caenorhabditis elegans in an energy deficient
      environment, extends the life-span and attenuates liver injury in aged mice. The
      present study examined whether late onset short-term treatment of daumone exerts
      anti-inflammatory effects in the livers of aged mice. Daumone was administered
      orally at doses of 2 or 20 mg/kg/day for 5 weeks to 24-month-old male C57BL/6J
      mice. Increased liver macrophage infiltration and gene expression of
      proinflammatory cytokines in aged mice were significantly attenuated by daumone
      treatment, suggesting that short-term oral administration of daumone may have
      hepatoprotective effects. Daumone also dose-dependently suppressed tumor necrosis
      factor-alpha (TNF-alpha)-induced nuclear factor-kappaB (NF-kappaB)
      phosphorylation in HepG2 cells. The present data demonstrated that short-term
      treatment of daumone has anti-inflammatory effects in aged mouse livers possibly
      through suppression of NF-kappaB signaling and suggest that daumone may become a
      lead compound targeting aging and age-associated diseases. 

PMID- 25954134
TI  - Effect of glutamate on the vestibulo-solitary projection after sodium
      nitroprusside-induced hypotension in conscious rats.
AB  - Orthostatic hypotension is most common in elderly people, and its prevalence
      increases with age. Attenuation of the vestibulo-sympathetic reflex (VSR) is
      commonly associated with orthostatic hypotension. In this study, we investigated
      the role of glutamate on the vestibulo-solitary projection of the VSR pathway to
      clarify the pathophysiology of orthostatic hypotension. Blood pressure and
      expression of both pERK and c-Fos protein were evaluated in the nucleus tractus
      solitarius (NTS) after microinjection of glutamate into the medial vestibular
      nucleus (MVN) in conscious rats with sodium nitroprusside (SNP)-induced
      hypotension that received baroreceptor unloading via sinoaortic denervation
      (SAD). SNP-induced hypotension increased the expression of both pERK and c-Fos
      protein in the NTS, which was abolished by pretreatment with glutamate receptor
      antagonists (MK801 or CNQX) in the MVN. Microinjection of glutamate receptor
      agonists (NMDA or AMPA) into the MVN increased the expression of both pERK and c
      Fos protein in the NTS without causing changes in blood pressure. These results
      indicate that both NMDA and AMPA receptors play a significant role in the
      vestibulo-solitary projection of the VSR pathway for maintaining blood pressure,
      and that glutamatergic transmission in this projection might play a key role in
      the pathophysiology of orthostatic hypotension. 

PMID- 25954136
TI  - Bacterial PAMPs and Allergens Trigger Increase in [Ca(2+)]i-induced Cytokine
      Expression in Human PDL Fibroblasts.
AB  - An oral environment is constantly exposed to environmental factors and
      microorganisms. The periodontal ligament (PDL) fibroblasts within this
      environment are subject to bacterial infection and allergic reaction. However,
      how these condition affect PDL fibroblasts has yet to be elucidated. PDL
      fibroblasts were isolated from healthy donors. We examined using reverse
      transcription-polymerase chain reaction and measuring the intracellular Ca(2+)
      concentration ([Ca(2+)]i). This study investigated the receptors activated by
      exogenous bacterial pathogens (Lipopolysaccharide and peptidoglycan) and
      allergens (German cockroach extract and house dust mite) as well as these
      pathogenic mediators-induced effects on the intracellular Ca(2+) signaling in
      human PDL fibroblasts. Moreover, we evaluated the expression of pro-inflammatory
      cytokines (interleukin (IL)-1beta, IL-6, and IL-8) and bone remodeling mediators
      (receptor activator of NF-kappaB ligand and osteoprotegerin) and intracellular
      Ca(2+)-involved effect. Bacterial pathogens and allergic mediators induced
      increased expression of pro-inflammatory cytokines, and these results are
      dependent on intracellular Ca(2+). However, bacterial pathogens and allergic
      mediators did not lead to increased expression of bone remodeling mediators,
      except lipopolysaccharide-induced effect on receptor activator of NF-kappaB
      ligand expression. These experiments provide evidence that a pathogens and
      allergens-induced increase in [Ca(2+)]i affects the inflammatory response in
      human PDL fibroblasts. 

PMID- 25954135
TI  - Improvement Characteristics of Bio-active Materials Coated Fabric on Rat Muscular
      Mitochondria.
AB  - This study surveys the improvement characteristics in old-aged muscular
      mitochondria by bio-active materials coated fabric (BMCF). To observe the
      effects, the fabric (10 and 30%) was worn to old-aged rat then the oxygen
      consumption efficiency and copy numbers of mitochondria, and mRNA expression of
      apoptosis- and mitophagy-related genes were verified. By wearing the BMCF, the
      oxidative respiration significantly increased when using the 30% materials coated
      fabric. The mitochondrial DNA copy number significantly decreased and
      subsequently recovered in a dose-dependent manner. The respiratory control ratio
      to mitochondrial DNA copy number showed a dose-dependent increment. As times
      passed, Bax, caspase 9, PGC-1alpha and beta-actin increased, and Bcl-2 decreased
      in a dose-dependent manner. However, the BMCF can be seen to have had no effect
      on Fas receptor. PINK1 expression did not change considerably and was inclined to
      decrease in control group, but the expression was down-regulated then
      subsequently increased with the use of the BMCF in a dose-dependent manner.
      Caspase 3 increased and subsequently decreased in a dose-dependent manner. These
      results suggest that the BMCF invigorates mitophagy and improves mitochondrial
      oxidative respiration in skeletal muscle, and in early stage of apoptosis induced
      by the BMCF is not related to extrinsic death-receptor mediated but mitochondria
      mediated signaling pathway. 

PMID- 25954137
TI  - In-Depth Analyses of B Cell Signaling Through Tandem Mass Spectrometry of
      Phosphopeptides Enriched by PolyMAC.
AB  - Tandem mass spectrometry (MS/MS) has enabled researchers to analyze complex
      biological samples since the original concept inception. It facilitates the
      identification and quantification of modifications within tens of thousands of
      proteins in a single large-scale proteomic experiment. Phosphorylation analysis,
      as one of the most common and important post-translational modifications, has
      particularly benefited from such progress in the field. Here we showcase the
      technique through in-depth analyses of B cell signaling based on quantitative
      phosphoproteomics. As a complement to the previously described PolyMAC-Ti
      (polymer-based metal ion affinity capture using titanium) reagent, we introduce
      here PolyMAC-Fe, which utilizes a different metal ion, Fe(III). An extensive
      comparison using the different available MS/MS fragmentations techniques was made
      between PolyMAC-Fe, PolyMAC-Ti and IMAC (immobilized metal ion affinity
      chromatography) reagents in terms of specificity, reproducibility and type of
      phosphopeptides being enriched. PolyMAC-Fe based chelation demonstrated good
      selectivity and unique specificity toward phosphopeptides, making it useful in
      specialized applications. We have combined PolyMAC-Ti and PolyMAC-Fe, along with
      SILAC-based quantitation and large-scale fractionation, for quantitative B cell
      phosphoproteomic analyses. The complementary approach allowed us to identify a
      larger percentage of multiply phosphorylated peptides than with PolyMAC-Ti alone.
      Overall, out of 13,794 unique phosphorylation sites identified, close to 20% were
      dependent on BCR signaling. These sites were further mapped to a variety of major
      signaling networks, offering more detailed information about the biochemistry of
      B cell receptor engagement.

PMID- 25954138
TI  - SLPI knockdown induced pancreatic ductal adenocarcinoma cells proliferation and
      invasion.
AB  - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease and
      still continues to have the worst prognosis of all gastrointestinal malignancies.
      Reports have demonstrated that secretory leukocyte protease inhibitor (SLPI) is
      overexpressed in various cancers and may be a potential therapeutic strategy for
      the treatment of different cancers. However, the possible role of SLPI in PDAC is
      still unknown. In the present study, we investigate the effects of SLPI gene
      knockdown on the biological behavior of human pancreatic cancer cells. The
      expressions of SLPI were detected, by qRT-PCR and Western blot, in human PDAC
      tissues as well as AsPC-1, BxPC-3 and PANC-1 cells. After transfection with siRNA
      targeting to SLPI, SLPI expression was detected by qRT-PCR and Western blot in
      cells. Cell proliferation and apoptosis were also evaluated by MTT assay and flow
      cytometry (FCM). The trans-well assays were also employed to explore the effects
      of SLPI knockdown on the migration and invasion of PDAC cells in vitro. RESULTS:
      The expressions of SLPI derived from human PDAC and PDAC cell lines were
      significant higher than those of control groups, respectively (P < 0.05).
      Regression analysis showed elevated SLPI level was positive correlated with
      development of PDAC. The siRNA target to SLPI significantly decreased the
      expressions of SLPI in these PDAC cell lines. Following SLPI-siRNA transduction,
      the proliferative capacity of the AsPC-1, BxPC-3 and PANC-1 cells was
      significantly inhibitions, compared to the blank (PDAC-wild type cells) and
      negative (non-targeting scrambled siRNA transduced PDAC cells) control ones,
      respectively (P < 0.05). Moreover, SLPI knockdown significantly increased the
      apoptosis fractions and reduced the migration and invasion of PDAC cells in vitro
      (P < 0.05). CONCLUSIONS: The present study demonstrated that: i) SLPI played an
      important role in PDAC progression; ii) SLPI might be an important characteristic
      of malignant PDAC associated with migration and invasion in vitro; and iii) siRNA
      targeting to SLPI might be a potential therapeutic strategy for the treatment of
      PCC.

PMID- 25954139
TI  - Prevalence of positive atopy patch test in an unselected pediatric population.
AB  - BACKGROUND: In the latest decades, epidemiological studies on allergic disorders
      in children, including atopic dermatitis, rhinitis and asthma, demonstrated a
      continuous increase in prevalence. However, such studies are usually performed by
      questionnaires and, sometimes, by skin prick test or in vitro IgE tests, while
      the portion of allergy sustained by the cell-mediated mechanism is neglected,
      because the essential test, i.e. the atopy patch test is not performed. METHODS:
      This cross-sectional survey studied by a specific questionnaire, skin prick test
      and atopy patch test, an unselected population, represented by the entire
      scholastic population attending a Primary school and a Junior Secondary school in
      the rural town of San Marco in Lamis, 12.000 inhabitants (Puglia, Italy).
      RESULTS: Among the 456 subjects included, 78 (17.1 %) had a positive skin prick
      test and 57 (12.5 %) had a positive atopy patch test. In particular, 13.4 % of
      subjects were positive only to skin prick test and 8.8 % were positive only to
      atopy patch test. The allergen most frequently positive was the house dust mite,
      with 41 positive results to skin prick test and 55 to atopy patch test, while for
      pollen positive results concerned almost exclusively the skin prick test.
      CONCLUSIONS: This survey on an unselected population of children detected a
      prevalence of positive results to atopy patch test not so distant from the
      positive results to skin prick test, and in 8.8 % of subjects the atopy patch
      test was the only positive test. This would suggest to add the atopy patch test
      in future epidemiological studies on allergy, in order to avoid to overlook the
      not negligible portion of patients with T-cell-mediated allergy.

PMID- 25954140
TI  - An Update on Pulmonary Arterial Hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a progressive disease that ultimately
      leads to right heart failure and death. PAH is defined as a mean pulmonary
      arterial pressure >= 25 mm Hg with a pulmonary capillary wedge pressure <= 15 mm
      Hg at rest. The diagnosis of PAH is one of exclusion; diagnostics include an
      extensive history, serology, chest radiograph, pulmonary function tests,
      ventilation/perfusion scan, transthoracic echocardiogram, and right heart
      catheterization. Treatment and care of patients with PAH can be complex.
      Therefore, the nurse practitioner is an integral member of the healthcare team
      caring for PAH patients, helping to ensure seamless care and support.

PMID- 25954142
TI  - Commentary: "Posttraining ablation of adult-generated olfactory granule cells
      degrades odor-reward memories".

PMID- 25954141
TI  - GALA: group analysis leads to accuracy, a novel approach for solving the inverse
      problem in exploratory analysis of group MEG recordings.
AB  - Although MEG/EEG signals are highly variable between subjects, they allow
      characterizing systematic changes of cortical activity in both space and time.
      Traditionally a two-step procedure is used. The first step is a transition from
      sensor to source space by the means of solving an ill-posed inverse problem for
      each subject individually. The second is mapping of cortical regions consistently
      active across subjects. In practice the first step often leads to a set of active
      cortical regions whose location and timecourses display a great amount of
      interindividual variability hindering the subsequent group analysis. We propose
      Group Analysis Leads to Accuracy (GALA)-a solution that combines the two steps
      into one. GALA takes advantage of individual variations of cortical geometry and
      sensor locations. It exploits the ensuing variability in electromagnetic forward
      model as a source of additional information. We assume that for different
      subjects functionally identical cortical regions are located in close proximity
      and partially overlap and their timecourses are correlated. This relaxed
      similarity constraint on the inverse solution can be expressed within a
      probabilistic framework, allowing for an iterative algorithm solving the inverse
      problem jointly for all subjects. A systematic simulation study showed that GALA,
      as compared with the standard min-norm approach, improves accuracy of true
      activity recovery, when accuracy is assessed both in terms of spatial proximity
      of the estimated and true activations and correct specification of spatial extent
      of the activated regions. This improvement obtained without using any noise
      normalization techniques for both solutions, preserved for a wide range of
      between-subject variations in both spatial and temporal features of regional
      activation. The corresponding activation timecourses exhibit significantly higher
      similarity across subjects. Similar results were obtained for a real MEG dataset
      of face-specific evoked responses. 

PMID- 25954143
TI  - Role of MicroRNAs in innate neuroprotection mechanisms due to preconditioning of
      the brain.
AB  - Insults to the brain that are sub-threshold for damage activate endogenous
      protective pathways, which can temporarily protect the brain against a subsequent
      harmful episode. This mechanism has been named as tolerance and its protective
      effects have been shown in experimental models of ischemia and epilepsy. The
      preconditioning-stimulus can be a short period of ischemia or mild seizures
      induced by low doses of convulsant drugs. Gene-array profiling has shown that
      both ischemic and epileptic tolerance feature large-scale gene down-regulation
      but the mechanism are unknown. MicroRNAs are a class of small non-coding RNAs of
      ~20-22 nucleotides length which regulate gene expression at a post
      transcriptional level via mRNA degradation or inhibition of protein translation.
      MicroRNAs have been shown to be regulated after non-harmful and harmful stimuli
      in the brain and to contribute to neuroprotective mechanisms. This review focuses
      on the role of microRNAs in the development of tolerance following ischemic or
      epileptic preconditioning. 

PMID- 25954144
TI  - On impulsive integrated pest management models with stochastic effects.
AB  - We extend existing impulsive differential equation models for integrated pest
      management (IPM) by including stage structure for both predator and prey as well
      as by adding stochastic elements in the birth rate of the prey. Based on our
      model, we propose an approach that incorporates various competing stochastic
      components. This approach enables us to select a model with optimally determined
      weights for maximum accuracy and precision in parameter estimation. This is
      significant in the case of IPM because the proposed model accommodates varying
      unknown environmental and climatic conditions, which affect the resources needed
      for pest eradication. 

PMID- 25954146
TI  - Diffusion tensor imaging detects chronic microstructural changes in white and
      gray matter after traumatic brain injury in rat.
AB  - Traumatic brain injury (TBI) is a major cause of disability and death in people
      of all ages worldwide. An initial brain injury caused by external mechanical
      forces triggers a cascade of tissue changes that lead to a wide spectrum of
      symptoms and disabilities, such as cognitive deficits, mood or anxiety disorders,
      motor impairments, chronic pain, and epilepsy. We investigated the detectability
      of secondary injury at a chronic time-point using ex vivo diffusion tensor
      imaging (DTI) in a rat model of TBI, lateral fluid percussion (LFP) injury. Our
      analysis of ex vivo DTI data revealed persistent microstructural tissue changes
      in white matter tracts, such as the splenium of the corpus callosum, angular
      bundle, and internal capsule. Histologic examination revealed mainly loss of
      myelinated axons and/or iron accumulation. Gray matter areas in the thalamus
      exhibited an increase in fractional anisotropy associated with neurodegeneration,
      myelinated fiber loss, and/or calcifications at the chronic phase. In addition,
      we examined whether these changes could also be detected with in vivo settings at
      the same chronic time-point. Our results provide insight into DTI detection of
      microstructural changes in the chronic phase of TBI, and elucidate how these
      changes correlate with cellular level alterations. 

PMID- 25954145
TI  - Developmental programming of hypothalamic neuronal circuits: impact on energy
      balance control.
AB  - The prevalence of obesity in adults and children has increased globally at an
      alarming rate. Mounting evidence from both epidemiological studies and animal
      models indicates that adult obesity and associated metabolic disorders can be
      programmed by intrauterine and early postnatal environment- a phenomenon known as
      "fetal programming of adult disease." Data from nutritional intervention studies
      in animals including maternal under- and over-nutrition support the developmental
      origins of obesity and metabolic syndrome. The hypothalamic neuronal circuits
      located in the arcuate nucleus controlling appetite and energy expenditure are
      set early in life and are perturbed by maternal nutritional insults. In this
      review, we focus on the effects of maternal nutrition in programming permanent
      changes in these hypothalamic circuits, with experimental evidence from animal
      models of maternal under- and over-nutrition. We discuss the epigenetic
      modifications which regulate hypothalamic gene expression as potential molecular
      mechanisms linking maternal diet during pregnancy to the offspring's risk of
      obesity at a later age. Understanding these mechanisms in key metabolic genes may
      provide insights into the development of preventative intervention strategies. 

PMID- 25954148
TI  - Activated platelets release sphingosine 1-phosphate and induce hypersensitivity
      to noxious heat stimuli in vivo.
AB  - At the site of injury activated platelets release various mediators, one of which
      is sphingosine 1-phosphate (S1P). It was the aim of this study to explore whether
      activated human platelets had a pronociceptive effect in an in vivo mouse model
      and whether this effect was based on the release of S1P and subsequent activation
      of neuronal S1P receptors 1 or 3. Human platelets were prepared in different
      concentrations (10(5)/MUl, 10(6)/MUl, 10(7)/MUl) and assessed in mice with
      different genetic backgrounds (WT, S1P1 (fl/fl), SNS-S1P1 (-/-), S1P3 (-/-)).
      Intracutaneous injections of activated human platelets induced a significant,
      dose-dependent hypersensitivity to noxious thermal stimulation. The degree of
      heat hypersensitivity correlated with the platelet concentration as well as the
      platelet S1P content and the amount of S1P released upon platelet activation as
      measured with LC MS/MS. Despite the significant correlations between S1P and
      platelet count, no difference in paw withdrawal latency (PWL) was observed in
      mice with a global null mutation of the S1P3 receptor or a conditional deletion
      of the S1P1 receptor in nociceptive primary afferents. Furthermore,
      neutralization of S1P with a selective anti-S1P antibody did not abolish platelet
      induced heat hypersensitivity. Our results suggest that activated platelets
      release S1P and induce heat hypersensitivity in vivo. However, the platelet
      induced heat hypersensitivity was caused by mediators other than S1P. 

PMID- 25954149
TI  - Divergent cardio-ventilatory and locomotor effects of centrally and peripherally
      administered urotensin II and urotensin II-related peptides in trout.
AB  - The urotensin II (UII) gene family consists of four paralogous genes called UII,
      UII-related peptide (URP), URP1 and URP2. UII and URP peptides exhibit the same
      cyclic hexapeptide core sequence (CFWKYC) while the N- and C-terminal regions are
      variable. UII, URP1, and URP2 mRNAs are differentially expressed within the
      central nervous system of teleost fishes, suggesting that they may exert distinct
      functions. Although the cardiovascular, ventilatory and locomotor effects of UII
      have been described in teleosts, much less is known regarding the physiological
      actions of URPs. The goal of the present study was to compare the central and
      peripheral actions of picomolar doses (5-500 pmol) of trout UII, URP1, and URP2
      on cardio-ventilatory variables and locomotor activity in the unanesthetized
      trout. Compared to vehicle, intracerebroventricular injection of UII, URP1 and
      URP2 evoked a gradual increase in total ventilation (V TOT) reaching statistical
      significance for doses of 50 and 500 pmol of UII and URP1 but for only 500 pmol
      of URP2. In addition, UII, URP1 and URP2 provoked an elevation of dorsal aortic
      blood pressure (P DA) accompanied with tachycardia. All peptides caused an
      increase in locomotor activity (A CT), at a threshold dose of 5 pmol for UII and
      URP1, and 50 pmol for URP2. After intra-arterial (IA) injection, and in contrast
      to their central effects, only the highest dose of UII and URP1 significantly
      elevated V TOT and A CT. UII produced a dose-dependent hypertensive effect with
      concomitant bradycardia while URP1 increased P DA and heart rate after injection
      of only the highest dose of peptide. URP2 did not evoke any cardio-ventilatory or
      locomotor effect after IA injection. Collectively, these findings support the
      hypothesis that endogenous UII, URP1 and URP2 in the trout brain may act as
      neurotransmitters and/or neuromodulators acting synergistically or differentially
      to control the cardio-respiratory and locomotor systems. In the periphery, the
      only physiological actions of these peptides might be those related to the well
      known cardiovascular regulatory actions of UII. It remains to determine whether
      the observed divergent physiological effects of UII and URPs are due to
      differential interaction with the UT receptor or binding to distinct UT subtypes.

PMID- 25954147
TI  - Mechanisms of chemotherapy-induced behavioral toxicities.
AB  - While chemotherapeutic agents have yielded relative success in the treatment of
      cancer, patients are often plagued with unwanted and even debilitating side
      effects from the treatment which can lead to dose reduction or even cessation of
      treatment. Common side effects (symptoms) of chemotherapy include (i) cognitive
      deficiencies such as problems with attention, memory and executive functioning;
      (ii) fatigue and motivational deficit; and (iii) neuropathy. These symptoms often
      develop during treatment but can remain even after cessation of chemotherapy,
      severely impacting long-term quality of life. Little is known about the
      underlying mechanisms responsible for the development of these behavioral
      toxicities, however, neuroinflammation is widely considered to be one of the
      major mechanisms responsible for chemotherapy-induced symptoms. Here, we
      critically assess what is known in regards to the role of neuroinflammation in
      chemotherapy-induced symptoms. We also argue that, based on the available
      evidence, neuroinflammation is unlikely the only mechanism involved in the
      pathogenesis of chemotherapy-induced behavioral toxicities. We evaluate two other
      putative candidate mechanisms. To this end we discuss the mediating role of
      damage-associated molecular patterns (DAMPs) activated in response to
      chemotherapy-induced cellular damage. We also review the literature with respect
      to possible alternative mechanisms such as a chemotherapy-induced change in the
      bioenergetic status of the tissue involving changes in mitochondrial function in
      relation to chemotherapy-induced behavioral toxicities. Understanding the
      mechanisms that underlie the emergence of fatigue, neuropathy, and cognitive
      difficulties is vital to better treatment and long-term survival of cancer
      patients. 

PMID- 25954151
TI  - Alternative neural circuitry that might be impaired in the development of
      Alzheimer disease.
AB  - It is well established that some individuals with normal cognitive capacity have
      abundant senile plaques in their brains. It has been proposed that those
      individuals are resilient or have compensation factors to prevent cognitive
      decline. In this comment, we explore an alternative mechanism through which
      cognitive capacity is maintained. This mechanism could involve the impairment of
      alternative neural circuitry. Also, the proportion of molecules such as Abeta or
      tau protein present in different areas of the brain could be important. 

PMID- 25954152
TI  - Distinct effects of ubiquitin overexpression on NMJ structure and motor
      performance in mice expressing catalytically inactive USP14.
AB  - Ubiquitin-specific protease 14 (USP14) is a major deubiquitinating enzyme and a
      key determinant of neuromuscular junction (NMJ) structure and function. We have
      previously reported dramatic ubiquitin depletion in the nervous systems of the
      USP14-deficient ataxia (ax (J) ) mice and demonstrated that transgenic ubiquitin
      overexpression partially rescues the ax (J) neuromuscular phenotype. However,
      later work has shown that ubiquitin overexpression does not correct the ax (J)
      deficits in hippocampal short term plasticity, and that transgenic expression of
      a catalytically inactive form of USP14 in the nervous system mimics the
      neuromuscular phenotype observed in the ax (J) mice, but causes a only a modest
      reduction of free ubiquitin. Instead, increased ubiquitin conjugates and aberrant
      activation of pJNK are observed in the nervous systems of the USP14 catalytic
      mutant mice. In this report, we demonstrate that restoring free ubiquitin levels
      in the USP14 catalytic mutant mice improved NMJ structure and reduced pJNK
      accumulation in motor neuron terminals, but had a negative impact on measures of
      NMJ function, such as motor performance and muscle development. Transgenic
      expression of ubiquitin had a dose-dependent effect on NMJ function in wild type
      mice: moderate levels of overexpression improved NMJ function while more robust
      ubiquitin overexpression reduced muscle development and motor coordination.
      Combined, these results suggest that maintenance of free ubiquitin levels by
      USP14 contributes to NMJ structure, but that USP14 regulates NMJ function through
      a separate pathway. 

PMID- 25954150
TI  - Targeting glutamate uptake to treat alcohol use disorders.
AB  - Alcoholism is a serious public health concern that is characterized by the
      development of tolerance to alcohol's effects, increased consumption, loss of
      control over drinking and the development of physical dependence. This cycle is
      often times punctuated by periods of abstinence, craving and relapse. The
      development of tolerance and the expression of withdrawal effects, which manifest
      as dependence, have been to a great extent attributed to neuroadaptations within
      the mesocorticolimbic and extended amygdala systems. Alcohol affects various
      neurotransmitter systems in the brain including the adrenergic, cholinergic,
      dopaminergic, GABAergic, glutamatergic, peptidergic, and serotonergic systems.
      Due to the myriad of neurotransmitter and neuromodulator systems affected by
      alcohol, the efficacies of current pharmacotherapies targeting alcohol dependence
      are limited. Importantly, research findings of changes in glutamatergic
      neurotransmission induced by alcohol self- or experimenter-administration have
      resulted in a focus on therapies targeting glutamatergic receptors and
      normalization of glutamatergic neurotransmission. Glutamatergic receptors
      implicated in the effects of ethanol include the ionotropic glutamate receptors
      (AMPA, Kainate, and NMDA) and some metabotropic glutamate receptors. Regarding
      glutamatergic homeostasis, ceftriaxone, MS-153, and GPI-1046, which upregulate
      glutamate transporter 1 (GLT1) expression in mesocorticolimbic brain regions,
      reduce alcohol intake in genetic animal models of alcoholism. Given the
      hyperglutamatergic/hyperexcitable state of the central nervous system induced by
      chronic alcohol abuse and withdrawal, the evidence thus far indicates that a
      restoration of glutamatergic concentrations and activity within the
      mesocorticolimbic system and extended amygdala as well as multiple memory systems
      holds great promise for the treatment of alcohol dependence. 

PMID- 25954153
TI  - Retinal aging in the diurnal Chilean rodent (Octodon degus): histological,
      ultrastructural and neurochemical alterations of the vertical information
      processing pathway.
AB  - The retina is sensitive to age-dependent degeneration. To find suitable animal
      models to understand and map this process has particular importance. The degu
      (Octodon degus) is a diurnal rodent with dichromatic color vision. Its retinal
      structure is similar to that in humans in many respects, therefore, it is well
      suited to study retinal aging. Histological, cell type-specific and
      ultrastructural alterations were examined in 6-, 12- and 36-months old degus. The
      characteristic layers of the retina were present at all ages, but slightly
      loosened tissue structure could be observed in 36-month-old animals both at light
      and electron microscopic levels. Elevated Glial fibrillary acidic protein (GFAP)
      expression was observed in Muller glial cells in aging retinas. The number of rod
      bipolar cells and the ganglion cells was reduced in the aging specimens, while
      that of cone bipolar cells remained unchanged. Other age-related differences were
      detected at ultrastructural level: alteration of the retinal pigment epithelium
      and degenerated photoreceptor cells were evident. Ribbon synapses were sparse and
      often differed in morphology from those in the young animals. These results
      support our hypothesis that (i) the rod pathway seems to be more sensitive than
      the cone pathway to age-related cell loss; (ii) structural changes in the
      basement membrane of pigment epithelial cells can be one of the early signs of
      degenerative processes; (iii) the loss of synaptic proteins especially from those
      of the ribbon synapses are characteristic; and (iv) the degu retina may be a
      suitable model for studying retinal aging. 

PMID- 25954155
TI  - Inducible and combinatorial gene manipulation in mouse brain.
AB  - We have deployed recombinant adeno-associated viruses equipped with tetracycline
      controlled genetic switches to manipulate gene expression in mouse brain. Here,
      we show a combinatorial genetic approach for inducible, cell type-specific gene
      expression and Cre/loxP mediated gene recombination in different brain regions.
      Our chemical-genetic approach will help to investigate 'when', 'where', and 'how'
      gene(s) control neuronal circuit dynamics, and organize, for example, sensory
      signal processing, learning and memory, and behavior. 

PMID- 25954156
TI  - Macrophage recruitment and epithelial repair following hair cell injury in the
      mouse utricle.
AB  - The sensory organs of the inner ear possess resident populations of macrophages,
      but the function of those cells is poorly understood. In many tissues,
      macrophages participate in the removal of cellular debris after injury and can
      also promote tissue repair. The present study examined injury-evoked macrophage
      activity in the mouse utricle. Experiments used transgenic mice in which the gene
      for the human diphtheria toxin receptor (huDTR) was inserted under regulation of
      the Pou4f3 promoter. Hair cells in such mice can be selectively lesioned by
      systemic treatment with diphtheria toxin (DT). In order to visualize macrophages,
      Pou4f3-huDTR mice were crossed with a second transgenic line, in which one or
      both copies of the gene for the fractalkine receptor CX3CR1 were replaced with a
      gene for GFP. Such mice expressed GFP in all macrophages, and mice that were
      CX3CR1(GFP/GFP) lacked the necessary receptor for fractalkine signaling.
      Treatment with DT resulted in the death of ~70% of utricular hair cells within 7
      days, which was accompanied by increased numbers of macrophages within the
      utricular sensory epithelium. Many of these macrophages appeared to be actively
      engulfing hair cell debris, indicating that macrophages participate in the
      process of 'corpse removal' in the mammalian vestibular organs. However, we
      observed no apparent differences in injury-evoked macrophage numbers in the
      utricles of CX3CR1(+/GFP) mice vs. CX3CR1(GFP/GFP) mice, suggesting that
      fractalkine signaling is not necessary for macrophage recruitment in these
      sensory organs. Finally, we found that repair of sensory epithelia at short times
      after DT-induced hair cell lesions was mediated by relatively thin cables of F
      actin. After 56 days recovery, however, all cell-cell junctions were
      characterized by very thick actin cables. 

PMID- 25954154
TI  - Sensory hair cell death and regeneration in fishes.
AB  - Sensory hair cells are specialized mechanotransductive receptors required for
      hearing and vestibular function. Loss of hair cells in humans and other mammals
      is permanent and causes reduced hearing and balance. In the early 1980's, it was
      shown that hair cells continue to be added to the inner ear sensory epithelia in
      cartilaginous and bony fishes. Soon thereafter, hair cell regeneration was
      documented in the chick cochlea following acoustic trauma. Since then, research
      using chick and other avian models has led to great insights into hair cell death
      and regeneration. However, with the rise of the zebrafish as a model organism for
      studying disease and developmental processes, there has been an increased
      interest in studying sensory hair cell death and regeneration in its lateral line
      and inner ears. Advances derived from studies in zebrafish and other fish species
      include understanding the effect of ototoxins on hair cells and finding
      otoprotectants to mitigate ototoxin damage, the role of cellular proliferation
      vs. direct transdifferentiation during hair cell regeneration, and elucidating
      cellular pathways involved in the regeneration process. This review will
      summarize research on hair cell death and regeneration using fish models,
      indicate the potential strengths and weaknesses of these models, and discuss
      several emerging areas of future studies. 

PMID- 25954158
TI  - Commentary: "Comparison of spike parameters from optically identified GABAergic
      and glutamatergic neurons in sparse cortical cultures".

PMID- 25954157
TI  - Thrombin regulation of synaptic transmission and plasticity: implications for
      health and disease.
AB  - Thrombin, a serine protease involved in the blood coagulation cascade has been
      shown to affect neural function following blood-brain barrier breakdown. However,
      several lines of evidence exist that thrombin is also expressed in the brain
      under physiological conditions, suggesting an involvement of thrombin in the
      regulation of normal brain functions. Here, we review ours' as well as others'
      recent work on the role of thrombin in synaptic transmission and plasticity
      through direct or indirect activation of Protease-Activated Receptor-1 (PAR1).
      These studies propose a novel role of thrombin in synaptic plasticity, both in
      physiology as well as in neurological diseases associated with increased brain
      thrombin/PAR1 levels. 

PMID- 25954159
TI  - Accelerated intoxication of GABAergic synapses by botulinum neurotoxin A
      disinhibits stem cell-derived neuron networks prior to network silencing.
AB  - Botulinum neurotoxins (BoNTs) are extremely potent toxins that specifically
      cleave SNARE proteins in peripheral synapses, preventing neurotransmitter
      release. Neuronal responses to BoNT intoxication are traditionally studied by
      quantifying SNARE protein cleavage in vitro or monitoring physiological paralysis
      in vivo. Consequently, the dynamic effects of intoxication on synaptic behaviors
      are not well-understood. We have reported that mouse embryonic stem cell-derived
      neurons (ESNs) are highly sensitive to BoNT based on molecular readouts of
      intoxication. Here we study the time-dependent changes in synapse- and network
      level behaviors following addition of BoNT/A to spontaneously active networks of
      glutamatergic and GABAergic ESNs. Whole-cell patch-clamp recordings indicated
      that BoNT/A rapidly blocked synaptic neurotransmission, confirming that ESNs
      replicate the functional pathophysiology responsible for clinical botulism.
      Quantitation of spontaneous neurotransmission in pharmacologically isolated
      synapses revealed accelerated silencing of GABAergic synapses compared to
      glutamatergic synapses, which was consistent with the selective accumulation of
      cleaved SNAP-25 at GAD1(+) pre-synaptic terminals at early timepoints. Different
      latencies of intoxication resulted in complex network responses to BoNT/A
      addition, involving rapid disinhibition of stochastic firing followed by network
      silencing. Synaptic activity was found to be highly sensitive to SNAP-25
      cleavage, reflecting the functional consequences of the localized cleavage of the
      small subpopulation of SNAP-25 that is engaged in neurotransmitter release in the
      nerve terminal. Collectively these findings illustrate that use of synaptic
      function assays in networked neurons cultures offers a novel and highly sensitive
      approach for mechanistic studies of toxin:neuron interactions and synaptic
      responses to BoNT. 

PMID- 25954160
TI  - Erratum on: Neurogenesis in the embryonic and adult brain: same regulators,
      different roles.
AB  - [This corrects the article on p. 396 in vol. 8, PMID: 25505873.]. 

PMID- 25954161
TI  - Individual variability in the anatomical distribution of nodes participating in
      rich club structural networks.
AB  - With recent advances in computational analyses of structural neuroimaging, it is
      possible to comprehensively map neural connectivity, i.e., the brain connectome.
      The architectural organization of the connectome is believed to play an important
      role in several biological processes. Central to the conformation of the
      connectome are connectivity hubs, which are likely to be organized in accordance
      with the rich club phenomenon, as evidenced by graph theory analyses of neural
      architecture. It is yet unclear whether rich club connectivity hubs are
      consistently organized in the same anatomical framework across healthy adults. We
      constructed the brain connectome from 43 healthy adults, based on T1-weighted and
      diffusion tensor MRI data. Probabilistic fiber tractography was used to evaluate
      connectivity between each possible pair of cortical anatomical regions of
      interest. Connectivity hubs were identified in accordance with the rich club
      phenomenon applied to binarized matrices, and the variability in frequency of hub
      participation was assessed node-wise across all subjects. The anatomical location
      of nodes participating in rich club networks was fairly consistent across
      subjects. The most common locations for rich club nodes were identified in
      integrative areas, such as the cingulate and pericingulate regions, medial aspect
      of the occipital areas and precuneus; or else, they were found in important and
      specialized brain regions (such as the oribitofrontal cortex, caudate, fusiform
      gyrus, and hippocampus). Marked anatomical consistency exists across healthy
      brains in terms of nodal participation and location of rich club networks. The
      consistency of connections between integrative areas and specialized brain
      regions highlights a fundamental connectivity pattern shared among healthy
      brains. We propose that approaching brain connectivity with this framework of
      anatomical consistencies may have clinical implications for early detection of
      individual variability. 

PMID- 25954162
TI  - The discovery of dendritic spines by Cajal.
AB  - Dendritic spines were considered an artifact of the Golgi method until a brash
      Spanish histologist, Santiago Ramon y Cajal, bet his scientific career arguing
      that they were indeed real, correctly deducing their key role in mediating
      synaptic connectivity. This article reviews the historical context of the
      discovery of spines and the reasons behind Cajal's obsession with them, all the
      way till his deathbed. 

PMID- 25954164
TI  - Neuroprotective effects of DAHP and Triptolide in focal cerebral ischemia via
      apoptosis inhibition and PI3K/Akt/mTOR pathway activation.
AB  - Triptolide (TP), one of the major active components of the traditional Chinese
      herb Tripterygium wilfordii Hook F, and 2, 4-diamino-6-hydroxypyrimidine (DAHP),
      an inhibitor of tetrahydrobiopterin (BH4) synthesis, have been reported to have
      potent anti-inflammatory and immunosuppressive properties. However, the
      protective effects of TP and DAHP on cerebral ischemia have not been reported
      yet. In this study, we investigated the neuroprotective effects of TP and DAHP in
      a middle cerebral artery occlusion (MCAO) rat model. Furthermore, we examined
      whether the neuroprotective effects of TP and DAHP were associated with the
      inhibition of apoptosis through suppressing BH4 and inducible NOS (iNOS)
      synthesis or the activation of the phosphoinositide-3-kinase/serine-threonine
      kinase Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway. Our results
      showed that pretreatments with TP (0.2 mg/kg) and DAHP (0.5 g/kg) significantly
      reduced ischemic lesion volume, water content, and neuronal cell death compared
      with the vehicle MCAO rats. In addition, compared with the MCAO group, TP, and
      DAHP pretreatment groups significantly reduced astrocyte numbers, caspase-3,
      cleaved caspase-3, and NF-kappaB up-regulation, while increased Bcl-2 expression.
      Moreover, protein expressions of PI3K, Akt, and mTOR increased, while
      extracellular signal-regulated protein kinases 1 and 2 (ERK1 and ERK2)
      phosphorylation decreased in both the TP-treated rats and DAHP-treated rats.
      These results demonstrate that TP and DAHP can decrease cell apoptosis in focal
      cerebral ischemia rat brains and that the mechanism may be related to the
      activation of the PI3K/Akt/mTOR pathway and inactivation of the ERK1/2 pathway.
      Thus our hypothesis was reached PI3K/Akt/mTOR and ERK1/2 pathways may provide
      distinct cellular targets for a new generation of therapeutic agents for the
      treatment of stroke, and TP and DAHP may be potential neuroprotective agents for
      cerebral ischemia/reperfusion injury. 

PMID- 25954165
TI  - Waking up to the alarm: sleep, clocks, and making memory (s)tick.

PMID- 25954163
TI  - Role of developmental factors in hypothalamic function.
AB  - The hypothalamus is a brain region which regulates homeostasis by mediating
      endocrine, autonomic and behavioral functions. It is comprised of several nuclei
      containing distinct neuronal populations producing neuropeptides and
      neurotransmitters that regulate fundamental body functions including temperature
      and metabolic rate, thirst and hunger, sexual behavior and reproduction,
      circadian rhythm, and emotional responses. The identity, number and connectivity
      of these neuronal populations are established during the organism's development
      and are of crucial importance for normal hypothalamic function. Studies have
      suggested that developmental abnormalities in specific hypothalamic circuits can
      lead to obesity, sleep disorders, anxiety, depression and autism. At the
      molecular level, the development of the hypothalamus is regulated by
      transcription factors (TF), secreted growth factors, neuropeptides and their
      receptors. Recent studies in zebrafish and mouse have demonstrated that some of
      these molecules maintain their expression in the adult brain and subsequently
      play a role in the physiological functions that are regulated by hypothalamic
      neurons. Here, we summarize the involvement of some of the key developmental
      factors in hypothalamic development and function by focusing on the mouse and
      zebrafish genetic model organisms. 

PMID- 25954166
TI  - Short-term visual deprivation reduces interference effects of task-irrelevant
      facial expressions on affective prosody judgments.
AB  - Several studies have suggested that neuroplasticity can be triggered by short
      term visual deprivation in healthy adults. Specifically, these studies have
      provided evidence that visual deprivation reversibly affects basic perceptual
      abilities. The present study investigated the long-lasting effects of short-term
      visual deprivation on emotion perception. To this aim, we visually deprived a
      group of young healthy adults, age-matched with a group of non-deprived controls,
      for 3 h and tested them before and after visual deprivation (i.e., after 8 h on
      average and at 4 week follow-up) on an audio-visual (i.e., faces and voices)
      emotion discrimination task. To observe changes at the level of basic perceptual
      skills, we additionally employed a simple audio-visual (i.e., tone bursts and
      light flashes) discrimination task and two unimodal (one auditory and one visual)
      perceptual threshold measures. During the 3 h period, both groups performed a
      series of auditory tasks. To exclude the possibility that changes in emotion
      discrimination may emerge as a consequence of the exposure to auditory
      stimulation during the 3 h stay in the dark, we visually deprived an additional
      group of age-matched participants who concurrently performed unrelated (i.e.,
      tactile) tasks to the later tested abilities. The two visually deprived groups
      showed enhanced affective prosodic discrimination abilities in the context of
      incongruent facial expressions following the period of visual deprivation; this
      effect was partially maintained until follow-up. By contrast, no changes were
      observed in affective facial expression discrimination and in the basic
      perception tasks in any group. These findings suggest that short-term visual
      deprivation per se triggers a reweighting of visual and auditory emotional cues,
      which seems to possibly prevail for longer durations. 

PMID- 25954167
TI  - The effects of attention on the temporal integration of multisensory stimuli.
AB  - In unisensory contexts, spatially-focused attention tends to enhance perceptual
      processing. How attention influences the processing of multisensory stimuli,
      however, has been of much debate. In some cases, attention has been shown to be
      important for processes related to the integration of audio-visual stimuli, but
      in other cases such processes have been reported to occur independently of
      attention. To address these conflicting results, we performed three experiments
      to examine how attention interacts with a key facet of multisensory processing:
      the temporal window of integration (TWI). The first two experiments used a novel
      cued-spatial-attention version of the bounce/stream illusion, wherein two moving
      visual stimuli with intersecting paths tend to be perceived as bouncing off
      rather than streaming through each other when a brief sound occurs near in time.
      When the task was to report whether the visual stimuli appeared to bounce or
      stream, attention served to narrow this measure of the TWI and bias perception
      toward "streaming". When the participants' task was to explicitly judge the
      simultaneity of the sound with the intersection of the moving visual stimuli,
      however, the results were quite different. Specifically, attention served to
      mainly widen the TWI, increasing the likelihood of simultaneity perception, while
      also substantially increasing the simultaneity judgment accuracy when the stimuli
      were actually physically simultaneous. Finally, in Experiment 3, where the task
      was to judge the simultaneity of a simple, temporally discrete, flashed visual
      stimulus and the same brief tone pip, attention had no effect on the measured
      TWI. These results highlight the flexibility of attention in enhancing
      multisensory perception and show that the effects of attention on multisensory
      processing are highly dependent on the task demands and observer goals. 

PMID- 25954168
TI  - Altered explorative strategies and reactive coping style in the FSL rat model of
      depression.
AB  - Modeling depression in animals is based on the observation of behaviors
      interpreted as analog to human symptoms. Typical tests used in experimental
      depression research are designed to evoke an either-or outcome. It is known that
      explorative and coping strategies are relevant for depression, however these
      aspects are generally not considered in animal behavioral testing. Here we
      investigate the Flinders Sensitive Line (FSL), a rat model of depression,
      compared to the Sprague-Dawley (SD) rat in three independent tests where the
      animals are allowed to express a more extensive behavioral repertoire. The
      multivariate concentric square fieldTM (MCSF) and the novel cage tests evoke
      exploratory behaviors in a novel environment and the home cage change test evokes
      social behaviors in the re-establishment of a social hierarchy. In the MCSF test,
      FSL rats exhibited less exploratory drive and more risk-assessment behavior
      compared to SD rats. When re-exposed to the arena, FSL, but not SD rats,
      increased their exploratory behavior compared to the first trial and displayed
      risk-assessment behavior to the same extent as SD rats. Thus, the behavior of FSL
      rats was more similar to that of SDs when the rats were familiar with the arena.
      In the novel cage test FSL rats exhibited a reactive coping style, consistent
      with the reduced exploration observed in the MCSF. Reactive coping is associated
      with less aggressive behavior. Accordingly, FSL rats displayed less aggressive
      behavior in the home cage change test. Taken together, our data show that FSL
      rats express altered exploratory behavior and reactive coping style. Reduced
      interest is a core symptom of depression, and individuals with a reactive coping
      style are more vulnerable to the disease. Our results support the use of FSL rats
      as an animal model of depression and increase our understanding of the FSL rat
      beyond the behavioral dimensions targeted by the traditional depression-related
      tests. 

PMID- 25954169
TI  - Emotional face expression modulates occipital-frontal effective connectivity
      during memory formation in a bottom-up fashion.
AB  - This study investigated the role of bottom-up and top-down neural mechanisms in
      the processing of emotional face expression during memory formation. Functional
      brain imaging data was acquired during incidental learning of positive ("happy"),
      neutral and negative ("angry" or "fearful") faces. Dynamic Causal Modeling (DCM)
      was applied on the functional magnetic resonance imaging (fMRI) data to
      characterize effective connectivity within a brain network involving face
      perception (inferior occipital gyrus and fusiform gyrus) and successful memory
      formation related areas (hippocampus, superior parietal lobule, amygdala, and
      orbitofrontal cortex). The bottom-up models assumed processing of emotional face
      expression along feed forward pathways to the orbitofrontal cortex. The top-down
      models assumed that the orbitofrontal cortex processed emotional valence and
      mediated connections to the hippocampus. A subsequent recognition memory test
      showed an effect of negative emotion on the response bias, but not on memory
      performance. Our DCM findings showed that the bottom-up model family of effective
      connectivity best explained the data across all subjects and specified that
      emotion affected most bottom-up connections to the orbitofrontal cortex,
      especially from the occipital visual cortex and superior parietal lobule. Of
      those pathways to the orbitofrontal cortex the connection from the inferior
      occipital gyrus correlated with memory performance independently of valence. We
      suggest that bottom-up neural mechanisms support effects of emotional face
      expression and memory formation in a parallel and partially overlapping fashion. 

PMID- 25954170
TI  - Early handling and repeated cross-fostering have opposite effect on mouse
      emotionality.
AB  - Early life events have a crucial role in programming the individual phenotype and
      exposure to traumatic experiences during infancy can increase later risk for a
      variety of neuropsychiatric conditions, including mood and anxiety disorders.
      Animal models of postnatal stress have been developed in rodents to explore
      molecular mechanisms responsible for the observed short and long lasting
      neurobiological effects of such manipulations. The main aim of this study was to
      compare the behavioral and hormonal phenotype of young and adult animals exposed
      to different postnatal treatments. Outbred mice were exposed to (i) the classical
      Handling protocol (H: 15 min-day of separation from the mother from day 1 to 14
      of life) or to (ii) a Repeated Cross-Fostering protocol (RCF: adoption of litters
      from day 1 to 4 of life by different dams). Handled mice received more maternal
      care in infancy and showed the already described reduced emotionality at
      adulthood. Repeated cross fostered animals did not differ for maternal care
      received, but showed enhanced sensitivity to separation from the mother in
      infancy and altered respiratory response to 6% CO2 in breathing air in comparison
      with controls. Abnormal respiratory responses to hypercapnia are commonly found
      among humans with panic disorders (PD), and point to RCF-induced instability of
      the early environment as a valid developmental model for PD. The comparisons
      between short- and long-term effects of postnatal handling vs. RCF indicate that
      different types of early adversities are associated with different behavioral
      profiles, and evoke psychopathologies that can be distinguished according to the
      neurobiological systems disrupted by early-life manipulations. 

PMID- 25954171
TI  - Releasing stimuli and aggression in crickets: octopamine promotes escalation and
      maintenance but not initiation.
AB  - Biogenic amines have widespread effects on numerous behaviors, but their natural
      functions are often unclear. We investigated the role of octopamine (OA), the
      invertebrate analog of noradrenaline, on initiation and maintenance of aggression
      in male crickets of different social status. The key-releasing stimulus for
      aggression is antennal fencing between males, a behavior occurring naturally on
      initial contact. We show that mechanical antennal stimulation (AS) alone is
      sufficient to initiate an aggressive response (mandible threat display). The
      efficacy of AS as an aggression releasing stimulus was augmented in winners of a
      previous fight, but unaffected in losers. The efficacy of AS was not, however,
      influenced by OA receptor (OAR) agonists or antagonists, regardless of social
      status. Additional experiments indicate that the efficacy of AS is also not
      influenced by dopamine (DA) or serotonin (5HT). In addition to initiating an
      aggressive response, prior AS enhanced aggression exhibited in subsequent fights,
      whereby AS with a male antenna was now necessary, indicating a role for male
      contact pheromones. This priming effect of male-AS on subsequent aggression was
      dependent on OA since it was blocked by OAR-antagonists, and enhanced by OAR
      agonists. Together our data reveal that neither OA, DA nor 5HT are required for
      initiating aggression in crickets, nor do these amines influence the efficacy of
      the natural releasing stimulus to initiate aggression. OA's natural function is
      restricted to promoting escalation and maintenance of aggression once initiated,
      and this can be invoked by numerous experiences, including prior contact with a
      male antenna as shown here. 

PMID- 25954172
TI  - Aversive emotional interference impacts behavior and prefronto-striatal activity
      during increasing attentional control.
AB  - Earlier studies have demonstrated that emotional stimulation modulates
      attentional processing during goal-directed behavior and related activity of a
      brain network including the inferior frontal gyrus (IFG) and the caudate nucleus.
      However, it is not clear how emotional interference modulates behavior and brain
      physiology during variation in attentional control, a relevant question for
      everyday life situations in which both emotional stimuli and cognitive load vary.
      The aim of this study was to investigate the impact of negative emotions on
      behavior and activity in IFG and caudate nucleus during increasing levels of
      attentional control. Twenty two healthy subjects underwent event-related
      functional magnetic resonance imaging while performing a task in which neutral or
      fearful facial expressions were displayed before stimuli eliciting increasing
      levels of attentional control processing. Results indicated slower reaction time
      (RT) and greater right IFG activity when fearful compared with neutral facial
      expressions preceded the low level of attentional control. On the other hand,
      fearful facial expressions preceding the intermediate level of attentional
      control elicited faster behavioral responses and greater activity in the right
      and left sides of the caudate. Finally, correlation analysis indicated a
      relationship between behavioral correlates of attentional control after emotional
      interference and right IFG activity. All together, these results suggest that the
      impact of negative emotions on attentional processing is differentially elicited
      at the behavioral and physiological levels as a function of cognitive load. 

PMID- 25954174
TI  - Objective differentiation of neonatal EEG background grades using detrended
      fluctuation analysis.
AB  - A quantitative and objective assessment of background electroencephalograph (EEG)
      in sick neonates remains an everyday clinical challenge. We studied whether long
      range temporal correlations quantified by detrended fluctuation analysis (DFA)
      could be used in the neonatal EEG to distinguish different grades of abnormality
      in the background EEG activity. Long-term EEG records of 34 neonates were
      collected after perinatal asphyxia, and their background was scored in 1 h epochs
      (8 h in each neonate) as mild, moderate or severe. We applied DFA on 15 min long,
      non-overlapping EEG epochs (n = 1088) filtered from 3 to 8 Hz. Our formal
      feasibility study suggested that DFA exponent can be reliably assessed in only
      part of the EEG epochs, and in only relatively short time scales (10-60 s), while
      it becomes ambiguous if longer time scales are considered. This prompted further
      exploration whether paradigm used for quantifying multifractal DFA (MF-DFA) could
      be applied in a more efficient way, and whether metrics from MF-DFA paradigm
      could yield useful benchmark with existing clinical EEG gradings. Comparison of
      MF-DFA metrics showed a significant difference between three visually assessed
      background EEG grades. MF-DFA parameters were also significantly correlated to
      interburst intervals quantified with our previously developed automated detector.
      Finally, we piloted a monitoring application of MF-DFA metrics and showed their
      evolution during patient recovery from asphyxia. Our exploratory study showed
      that neonatal EEG can be quantified using multifractal metrics, which might offer
      a suitable parameter to quantify the grade of EEG background, or to monitor
      changes in brain state that take place during long-term brain monitoring. 

PMID- 25954173
TI  - Role of nucleosome remodeling in neurodevelopmental and intellectual disability
      disorders.
AB  - It is becoming increasingly important to understand how epigenetic mechanisms
      control gene expression during neurodevelopment. Two epigenetic mechanisms that
      have received considerable attention are DNA methylation and histone acetylation.
      Human exome sequencing and genome-wide association studies have linked several
      neurobiological disorders to genes whose products actively regulate DNA
      methylation and histone acetylation. More recently, a third major epigenetic
      mechanism, nucleosome remodeling, has been implicated in human developmental and
      intellectual disability (ID) disorders. Nucleosome remodeling is driven primarily
      through nucleosome remodeling complexes with specialized ATP-dependent enzymes.
      These enzymes directly interact with DNA or chromatin structure, as well as
      histone subunits, to restructure the shape and organization of nucleosome
      positioning to ultimately regulate gene expression. Of particular interest is the
      neuron-specific Brg1/hBrm Associated Factor (nBAF) complex. Mutations in nBAF
      subunit genes have so far been linked to Coffin-Siris syndrome (CSS), Nicolaides
      Baraitser syndrome (NBS), schizophrenia, and Autism Spectrum Disorder (ASD).
      Together, these human developmental and ID disorders are powerful examples of the
      impact of epigenetic modulation on gene expression. This review focuses on the
      new and emerging role of nucleosome remodeling in neurodevelopmental and ID
      disorders and whether nucleosome remodeling affects gene expression required for
      cognition independently of its role in regulating gene expression required for
      development. 

PMID- 25954175
TI  - Age-related slowing of response selection and production in a visual choice
      reaction time task.
AB  - Aging is associated with delayed processing in choice reaction time (CRT) tasks,
      but the processing stages most impacted by aging have not been clearly
      identified. Here, we analyzed CRT latencies in a computerized serial visual
      feature-conjunction task. Participants responded to a target letter (probability
      40%) by pressing one mouse button, and responded to distractor letters differing
      either in color, shape, or both features from the target (probabilities 20% each)
      by pressing the other mouse button. Stimuli were presented randomly to the left
      and right visual fields and stimulus onset asynchronies (SOAs) were adaptively
      reduced following correct responses using a staircase procedure. In Experiment 1,
      we tested 1466 participants who ranged in age from 18 to 65 years. CRT latencies
      increased significantly with age (r = 0.47, 2.80 ms/year). Central processing
      time (CPT), isolated by subtracting simple reaction times (SRT) (obtained in a
      companion experiment performed on the same day) from CRT latencies, accounted for
      more than 80% of age-related CRT slowing, with most of the remaining increase in
      latency due to slowed motor responses. Participants were faster and more accurate
      when the stimulus location was spatially compatible with the mouse button used
      for responding, and this effect increased slightly with age. Participants took
      longer to respond to distractors with target color or shape than to distractors
      with no target features. However, the additional time needed to discriminate the
      more target-like distractors did not increase with age. In Experiment 2, we
      replicated the findings of Experiment 1 in a second population of 178
      participants (ages 18-82 years). CRT latencies did not differ significantly in
      the two experiments, and similar effects of age, distractor similarity, and
      stimulus-response spatial compatibility were found. The results suggest that the
      age-related slowing in visual CRT latencies is largely due to delays in response
      selection and production. 

PMID- 25954176
TI  - A multisensory perspective of working memory.
AB  - Although our sensory experience is mostly multisensory in nature, research on
      working memory representations has focused mainly on examining the senses in
      isolation. Results from the multisensory processing literature make it clear that
      the senses interact on a more intimate manner than previously assumed. These
      interactions raise questions regarding the manner in which multisensory
      information is maintained in working memory. We discuss the current status of
      research on multisensory processing and the implications of these findings on our
      theoretical understanding of working memory. To do so, we focus on reviewing
      working memory research conducted from a multisensory perspective, and discuss
      the relation between working memory, attention, and multisensory processing in
      the context of the predictive coding framework. We argue that a multisensory
      approach to the study of working memory is indispensable to achieve a realistic
      understanding of how working memory processes maintain and manipulate
      information. 

PMID- 25954177
TI  - Mechanisms underlying selecting objects for action.
AB  - We assessed the factors which affect the selection of objects for action,
      focusing on the role of action knowledge and its modulation by distracters.
      Fourteen neuropsychological patients and 10 healthy aged-matched controls
      selected pairs of objects commonly used together among distracters in two
      contexts: with real objects and with pictures of the same objects presented
      sequentially on a computer screen. Across both tasks, semantically related
      distracters led to slower responses and more errors than unrelated distracters
      and the object actively used for action was selected prior to the object that
      would be passively held during the action. We identified a sub-group of patients
      (N = 6) whose accuracy was 2SDs below the controls performances in the real
      object task. Interestingly, these impaired patients were more affected by the
      presence of unrelated distracters during both tasks than intact patients and
      healthy controls. Note that the impaired patients had lesions to left parietal,
      right anterior temporal and bilateral pre-motor regions. We conclude that: (1)
      motor procedures guide object selection for action, (2) semantic knowledge
      affects action-based selection, (3) impaired action decision making is associated
      with the inability to ignore distracting information and (4) lesions to either
      the dorsal or ventral visual stream can lead to deficits in making action
      decisions. Overall, the data indicate that impairments in everyday tasks can be
      evaluated using a simulated computer task. The implications for rehabilitation
      are discussed. 

PMID- 25954178
TI  - Individualized treatment with transcranial direct current stimulation in patients
      with chronic non-fluent aphasia due to stroke.
AB  - While evidence suggests that transcranial direct current stimulation (tDCS) may
      facilitate language recovery in chronic post-stroke aphasia, individual
      variability in patient response to different patterns of stimulation remains
      largely unexplored. We sought to characterize this variability among chronic
      aphasic individuals, and to explore whether repeated stimulation with an
      individualized optimal montage could lead to persistent reduction of aphasia
      severity. In a two-phase study, we first stimulated patients with four active
      montages (left hemispheric anode or cathode; right hemispheric anode or cathode)
      and one sham montage (Phase 1). We examined changes in picture naming ability to
      address (1) variability in response to different montages among our patients, and
      (2) whether individual patients responded optimally to at least one montage.
      During Phase 2, subjects who responded in Phase 1 were randomized to receive
      either real-tDCS or to receive sham stimulation (10 days); patients who were
      randomized to receive sham stimulation first were then crossed over to receive
      real-tDCS (10 days). In both phases, 2 mA tDCS was administered for 20 min per
      real-tDCS sessions and patients performed a picture naming task during
      stimulation. Patients' language ability was re-tested after 2-weeks and 2-months
      following real and sham tDCS in Phase 2. In Phase 1, despite considerable
      individual variability, the greatest average improvement was observed after left
      cathodal stimulation. Seven out of 12 subjects responded optimally to at least
      one montage as demonstrated by transient improvement in picture-naming. In Phase
      2, aphasia severity improved at 2-weeks and 2-months following real-tDCS but not
      sham. Despite individual variability with respect to optimal tDCS approach,
      certain montages result in consistent transient improvement in persons with
      chronic post-stroke aphasia. This preliminary study supports the notion that
      individualized tDCS treatment may enhance aphasia recovery in a persistent
      manner. 

PMID- 25954179
TI  - Mathematics anxiety reduces default mode network deactivation in response to
      numerical tasks.
AB  - Mathematics anxiety is negatively related to mathematics performance, thereby
      threatening the professional success. Preoccupation with the emotional content of
      the stimuli may consume working memory resources, which may be reflected in
      decreased deactivation of areas associated with the default mode network (DMN)
      activated during self-referential and emotional processing. The common problem is
      that math anxiety is usually associated with poor math performance, so that any
      group differences are difficult to interpret. Here we compared the BOLD-response
      of 18 participants with high (HMAs) and 18 participants with low mathematics
      anxiety (LMAs) matched for their mathematical performance to two numerical tasks
      (number comparison, number bisection). During both tasks, we found stronger
      deactivation within the DMN in LMAs compared to HMAs, while BOLD-response in task
      related activation areas did not differ between HMAs and LMAs. The difference in
      DMN deactivation between the HMA and LMA group was more pronounced in stimuli
      with additional requirement on inhibitory functions, but did not differ between
      number magnitude processing and arithmetic fact retrieval. 

PMID- 25954180
TI  - Understanding visual consciousness in autism spectrum disorders.
AB  - The paper focuses on the question of what the (visual) perceptual differences are
      between individuals with autism spectrum disorders (ASD) and typically developing
      (TD) individuals. We argue against the view that autistic subjects have a
      deficiency in the most basic form of perceptual consciousness-namely, phenomenal
      consciousness. Instead, we maintain, the perceptual atypicality of individuals
      with autism is of a more conceptual and cognitive sort-their perceptual
      experiences share crucial aspects with TD individuals. Our starting point is Ben
      Shalom's (2005, 2009) three-level processing framework for explaining atypicality
      in several domains of processing among autistics, which we compare with two other
      tripartite models of perception-Jackendoff's (1987) and Prinz's (2000, 2005a,
      2007) Intermediate Level Hypothesis and Lamme's (2004, 2006, 2010) neural account
      of consciousness. According to these models, whereas the second level of
      processing is concerned with viewer-centered visual representations of basic
      visual properties and incorporates some early forms of integration, the third
      level is more cognitive and conceptual. We argue that the data suggest that the
      atypicality in autism is restricted mainly to the third level. More specifically,
      second-level integration, which is the mark of phenomenal consciousness, is
      typical, yet third-level integration of perceptual objects and concepts is
      atypical. Thus, the basic experiences of individuals with autism are likely to be
      similar to typical subjects' experiences; the main difference lies in the sort of
      cognitive access the subjects have to their experiences. We conclude by
      discussing implications of the suggested analysis of experience in autism for
      conceptions of phenomenal consciousness. 

PMID- 25954181
TI  - What visual illusions tell us about underlying neural mechanisms and observer
      strategies for tackling the inverse problem of achromatic perception.
AB  - Research in lightness perception centers on understanding the prior assumptions
      and processing strategies the visual system uses to parse the retinal intensity
      distribution (the proximal stimulus) into the surface reflectance and
      illumination components of the scene (the distal stimulus-ground truth). It is
      agreed that the visual system must compare different regions of the visual image
      to solve this inverse problem; however, the nature of the comparisons and the
      mechanisms underlying them are topics of intense debate. Perceptual illusions are
      of value because they reveal important information about these visual processing
      mechanisms. We propose a framework for lightness research that resolves
      confusions and paradoxes in the literature, and provides insight into the
      mechanisms the visual system employs to tackle the inverse problem. The main idea
      is that much of the debate and confusion in the literature stems from the fact
      that lightness, defined as apparent reflectance, is underspecified and refers to
      three different types of judgments that are not comparable. Under stimulus
      conditions containing a visible illumination component, such as a shadow
      boundary, observers can distinguish and match three independent dimensions of
      achromatic experience: apparent intensity (brightness), apparent local intensity
      ratio (brightness-contrast), and apparent reflectance (lightness). In the absence
      of a visible illumination boundary, however, achromatic vision reduces to two
      dimensions and, depending on stimulus conditions and observer instructions,
      judgments of lightness are identical to judgments of brightness or brightness
      contrast. Furthermore, because lightness judgments are based on different
      information under different conditions, they can differ greatly in their degree
      of difficulty and in their accuracy. This may, in part, explain the large
      variability in lightness constancy across studies. 

PMID- 25954182
TI  - Cascaded processing in written compound word production.
AB  - In this study we investigated the intricate interplay between central linguistic
      processing and peripheral motor processes during typewriting. Participants had to
      typewrite two-constituent (noun-noun) Finnish compounds in response to picture
      presentation while their typing behavior was registered. As dependent measures we
      used writing onset time to assess what processes were completed before writing
      and inter-key intervals to assess what processes were going on during writing. It
      was found that writing onset time was determined by whole word frequency rather
      than constituent frequencies, indicating that compound words are retrieved as
      whole orthographic units before writing is initiated. In addition, we found that
      the length of the first syllable also affects writing onset time, indicating that
      the first syllable is fully prepared before writing commences. The inter-key
      interval results showed that linguistic planning is not fully ready before
      writing, but cascades into the motor execution phase. More specifically, inter
      key intervals were largest at syllable and morpheme boundaries, supporting the
      view that additional linguistic planning takes place at these boundaries. Bigram
      and trigram frequency also affected inter-key intervals with shorter intervals
      corresponding to higher frequencies. This can be explained by stronger memory
      traces for frequently co-occurring letter sequences in the motor memory for
      typewriting. These frequency effects were even larger in the second than in the
      first constituent, indicating that low-level motor memory starts to become more
      important during the course of writing compound words. We discuss our results in
      the light of current models of morphological processing and written word
      production. 

PMID- 25954183
TI  - EMDR therapy for PTSD after motor vehicle accidents: meta-analytic evidence for
      specific treatment.
AB  - Motor vehicle accident (MVA) victims may suffer both acute and post-traumatic
      stress disorders (PTSD). With PTSD affecting social, interpersonal and
      occupational functioning, clinicians as well as the National Institute of Health
      are very interested in identifying the most effective psychological treatment to
      reduce PTSD. From research findings, eye movement desensitization and
      reprocessing (EMDR) therapy is considered as one of the effective treatment of
      PTSD. In this paper, we present the results of a meta-analysis of fMRI studies on
      PTSD after MVA through activation likelihood estimation. We found that PTSD
      following MVA is characterized by neural modifications in the anterior cingulate
      cortex (ACC), a cerebral structure involved in fear-conditioning mechanisms.
      Basing on previous findings in both humans and animals, which demonstrate that
      desensitization techniques and extinction protocols act on the limbic system, the
      effectiveness of EMDR and of cognitive behavioral therapies (CBT) may be related
      to the fact that during these therapies the ACC is stimulated by desensitization.

PMID- 25954185
TI  - Compression and suppression as instances of a similar mechanism affecting tactile
      perception during movement.

PMID- 25954184
TI  - Altered cerebellar connectivity in Parkinson's patients ON and OFF L-DOPA
      medication.
AB  - Although nigrostriatal changes are most commonly affiliated with Parkinson's
      disease, the role of the cerebellum in Parkinson's has become increasingly
      apparent. The present study used lobule-based cerebellar resting state functional
      connectivity to (1) compare cerebellar-whole brain and cerebellar-cerebellar
      connectivity in Parkinson's patients both ON and OFF L-DOPA medication and
      controls, and to (2) relate variations in cerebellar connectivity to behavioral
      performance. Results indicated that, when contrasted to the control group,
      Parkinson's patients OFF medication had increased levels of cerebellar-whole
      brain and cerebellar-cerebellar connectivity, whereas Parkinson's patients ON
      medication had decreased levels of cerebellar-whole brain and cerebellar
      cerebellar connectivity. Moreover, analyses relating levels of cerebellar
      connectivity to behavioral measures demonstrated that, within each group,
      increased levels of connectivity were most often associated with improved
      cognitive and motor performance, but there were several instances where increased
      connectivity was related to poorer performance. Overall, the present study found
      medication-variant cerebellar connectivity in Parkinson's patients, further
      demonstrating cerebellar changes associated with Parkinson's disease and the
      moderating effects of medication. 

PMID- 25954187
TI  - The L2 decomposition of transparent derived verbs - Is it 'morphological'? A
      commentary on De Grauwe, Lemhofer, Willems, & Schriefers (2014).

PMID- 25954186
TI  - Brain activity classifies adolescents with and without a familial history of
      substance use disorders.
AB  - We aimed to uncover differences in brain circuits of adolescents with parental
      positive or negative histories of substance use disorders (SUD), when performing
      a task that elicits emotional conflict, testing whether the brain circuits could
      serve as endophenotype markers to distinguish these adolescents. We acquired
      functional magnetic resonance imaging data from 11 adolescents with a positive
      familial history of SUD (FH+ group) and seven adolescents with a negative
      familial history of SUD (FH- group) when performing an emotional stroop task. We
      extracted brain features from the conflict-related contrast images in group level
      analyses and granger causality indices (GCIs) that measure the causal
      interactions among regions. Support vector machine (SVM) was applied to classify
      the FH+ and FH- adolescents. Adolescents with FH+ showed greater activity and
      weaker connectivity related to emotional conflict, decision making and reward
      system including anterior cingulate cortex (ACC), prefrontal cortex (PFC), and
      ventral tegmental area (VTA). High classification accuracies were achieved with
      leave-one-out cross validation (89.75% for the maximum conflict, 96.71% when
      combining maximum conflict and general conflict contrast, 97.28% when combining
      activity of the two contrasts and GCIs). Individual contributions of the brain
      features to the classification were further investigated, indicating that
      activation in PFC, ACC, VTA and effective connectivity from PFC to ACC play the
      most important roles. We concluded that fundamental differences of neural
      substrates underlying cognitive behaviors of adolescents with parental positive
      or negative histories of SUD provide new insight into potential neurobiological
      mechanisms contributing to the elevated risk of FH+ individuals for developing
      SUD. 

PMID- 25954188
TI  - Erratum on: Habit and embodiment in Merleau-Ponty.
AB  - [This corrects the article on p. 542 in vol. 8, PMID: 25120448.]. 

PMID- 25954189
TI  - Shape representations in the primate dorsal visual stream.
AB  - The primate visual system extracts object shape information for object
      recognition in the ventral visual stream. Recent research has demonstrated that
      object shape is also processed in the dorsal visual stream, which is specialized
      for spatial vision and the planning of actions. A number of studies have
      investigated the coding of 2D shape in the anterior intraparietal area (AIP), one
      of the end-stage areas of the dorsal stream which has been implicated in the
      extraction of affordances for the purpose of grasping. These findings challenge
      the current understanding of area AIP as a critical stage in the dorsal stream
      for the extraction of object affordances. The representation of three-dimensional
      (3D) shape has been studied in two interconnected areas known to be critical for
      object grasping: area AIP and area F5a in the ventral premotor cortex (PMv), to
      which AIP projects. In both areas neurons respond selectively to 3D shape defined
      by binocular disparity, but the latency of the neural selectivity is
      approximately 10 ms longer in F5a compared to AIP, consistent with its higher
      position in the hierarchy of cortical areas. Furthermore, F5a neurons were more
      sensitive to small amplitudes of 3D curvature and could detect subtle differences
      in 3D structure more reliably than AIP neurons. In both areas, 3D-shape selective
      neurons were co-localized with neurons showing motor-related activity during
      object grasping in the dark, indicating a close convergence of visual and motor
      information on the same clusters of neurons. 

PMID- 25954190
TI  - On the role of spatial phase and phase correlation in vision, illusion, and
      cognition.
AB  - Numerous findings indicate that spatial phase bears an important cognitive
      information. Distortion of phase affects topology of edge structures and makes
      images unrecognizable. In turn, appropriately phase-structured patterns give rise
      to various illusions of virtual image content and apparent motion. Despite a
      large body of phenomenological evidence not much is known yet about the role of
      phase information in neural mechanisms of visual perception and cognition. Here,
      we are concerned with analysis of the role of spatial phase in computational and
      biological vision, emergence of visual illusions and pattern recognition. We
      hypothesize that fundamental importance of phase information for invariant
      retrieval of structural image features and motion detection promoted development
      of phase-based mechanisms of neural image processing in course of evolution of
      biological vision. Using an extension of Fourier phase correlation technique, we
      show that the core functions of visual system such as motion detection and
      pattern recognition can be facilitated by the same basic mechanism. Our analysis
      suggests that emergence of visual illusions can be attributed to presence of
      coherently phase-shifted repetitive patterns as well as the effects of acuity
      compensation by saccadic eye movements. We speculate that biological vision
      relies on perceptual mechanisms effectively similar to phase correlation, and
      predict neural features of visual pattern (dis)similarity that can be used for
      experimental validation of our hypothesis of "cognition by phase correlation." 

PMID- 25954191
TI  - Spiking neuron network Helmholtz machine.
AB  - An increasing amount of behavioral and neurophysiological data suggests that the
      brain performs optimal (or near-optimal) probabilistic inference and learning
      during perception and other tasks. Although many machine learning algorithms
      exist that perform inference and learning in an optimal way, the complete
      description of how one of those algorithms (or a novel algorithm) can be
      implemented in the brain is currently incomplete. There have been many proposed
      solutions that address how neurons can perform optimal inference but the question
      of how synaptic plasticity can implement optimal learning is rarely addressed.
      This paper aims to unify the two fields of probabilistic inference and synaptic
      plasticity by using a neuronal network of realistic model spiking neurons to
      implement a well-studied computational model called the Helmholtz Machine. The
      Helmholtz Machine is amenable to neural implementation as the algorithm it uses
      to learn its parameters, called the wake-sleep algorithm, uses a local delta
      learning rule. Our spiking-neuron network implements both the delta rule and a
      small example of a Helmholtz machine. This neuronal network can learn an internal
      model of continuous-valued training data sets without supervision. The network
      can also perform inference on the learned internal models. We show how various
      biophysical features of the neural implementation constrain the parameters of the
      wake-sleep algorithm, such as the duration of the wake and sleep phases of
      learning and the minimal sample duration. We examine the deviations from optimal
      performance and tie them to the properties of the synaptic plasticity rule. 

PMID- 25954192
TI  - Forever young: rejuvenating muscle satellite cells.
AB  - A hallmark of aging is alteration of organismal homeostasis and progressive
      decline of tissue functions. Alterations of both cell intrinsic functions and
      regenerative environmental cues contribute to the compromised stem cell activity
      and reduced regenerative capability occurring in aged muscles. In this
      perspective, we discuss the new evidence supporting the hypothesis that skeletal
      muscle stem cells (MuSCs) are intrinsically defective in elderly muscles. In
      particular, we review three recent papers leading to identify fibroblast growth
      factor receptor-1, p38 mitogen-activated protein kinase, and p16INK4a as altered
      signaling in satellite cells from aged mice. These pathways contribute to age
      related loss of MuSCs asymmetric polarization, compromised self-renewal capacity,
      and acquisition of pre-senescent state. The pharmacological manipulation of those
      networks can open novel strategies to rejuvenate MuSCs and counteract the
      functional decline of skeletal muscle during aging. 

PMID- 25954193
TI  - Reliability of a novel serious game using dual-task gait profiles to early
      characterize aMCI.
AB  - BACKGROUND: As the population of older adults is growing, the interest in a
      simple way to detect characterize amnestic mild cognitive impairment (aMCI), a
      prodromal stage of Alzheimer's disease (AD), is becoming increasingly important.
      Serious game (SG) -based cognitive and motor performance profiles while
      performing everyday activities and dual-task walking (DTW) "motor signatures" are
      two very promising markers that can be detected in predementia states. We aim to
      compare the consistency, or conformity, of measurements made by a custom SG with
      DTW (NAV), a SG without DTW (DOT), neuropsychological measures and genotyping as
      markers for early detection of aMCI. METHODS: The study population included three
      groups: early AD (n = 86), aMCI (n = 65), and healthy control subjects (n = 76),
      who completed the custom SG tasks in three separate sessions over a 3-month
      period. Outcome measures were neuropsychological data across-domain and within
      domain intra-individual variability (IIV) and DOT and NAV latency-based and
      accuracy-based IIV. IIV reflects a transient, within-person change in behavioral
      performance, either during different cognitive domains (across-domain) or within
      the same domain (within-domain). Test-retest reliability of the DOT and NAV
      markers were assessed using an intraclass correlation (ICC) analysis. RESULTS:
      RESULTS indicated that performance data, such as the NAV latency-based and
      accuracy-based IIV, during the task displayed greater reliability across sessions
      compared to DOT. During the NAV task-engagement, the executive function,
      planning, and motor performance profiles exhibited moderate to good reliability
      (ICC = 0.6-0.8), while during DOT, executive function and spatial memory accuracy
      profiles exhibited fair to moderate reliability (ICC = 0.3-0.6). Additionally,
      reliability across tasks was more stable when three sessions were used in the ICC
      calculation relative to two sessions. DISCUSSION: Our findings suggest that
      "motor signature" data during the NAV tasks were a more reliable marker for early
      diagnosis of aMCI than DOT. This result accentuates the importance of utilizing
      motor performance data as a metric for aMCI populations where memory decline is
      often the behavioral outcome of interest. In conclusion, custom SG with DTW
      performance data provide an ecological and reliable approach for cognitive
      assessment across multiple sessions and thus can be used as a useful tool for
      tracking longitudinal change in observational and interventional studies on aMCI.

PMID- 25954195
TI  - Determinants of frailty: the added value of assessing medication.
AB  - This study aims to analyze which determinants predict frailty in general and each
      frailty domain (physical, psychological, and social), considering the integral
      conceptual model of frailty, and particularly to examine the contribution of
      medication in this prediction. A cross-sectional study was designed using a non
      probabilistic sample of 252 community-dwelling elderly from three Portuguese
      cities. Frailty and determinants of frailty were assessed with the Tilburg
      Frailty Indicator. The amount and type of different daily-consumed medication
      were also examined. Hierarchical regression analysis were conducted. The mean age
      of the participants was 79.2 years (+/-7.3), and most of them were women (75.8%),
      widowed (55.6%) and with a low educational level (0-4 years: 63.9%). In this
      study, determinants explained 46% of the variance of total frailty, and 39.8,
      25.3, and 27.7% of physical, psychological, and social frailty respectively. Age,
      gender, income, death of a loved one in the past year, lifestyle, satisfaction
      with living environment and self-reported comorbidity predicted total frailty,
      while each frailty domain was associated with a different set of determinants.
      The number of daily-consumed drugs was independently associated with physical
      frailty, and the consumption of medication for the cardiovascular system and for
      the blood and blood-forming organs explained part of the variance of total and
      physical frailty. The adverse effects of polymedication and its direct link with
      the level of comorbidities could explain the independent contribution of the
      amount of prescribed drugs to frailty prediction. On the other hand, findings in
      regard to medication type provide further evidence of the association of frailty
      with cardiovascular risk. In the present study, a significant part of frailty was
      predicted, and the different contributions of each determinant to frailty domains
      highlight the relevance of the integral model of frailty. The added value of a
      simple assessment of medication was considerable, and it should be taken into
      account for effective identification of frailty. 

PMID- 25954194
TI  - Long-chain omega-3 fatty acids and the brain: a review of the independent and
      shared effects of EPA, DPA and DHA.
AB  - Omega-3 polyunsaturated fatty acids (PUFAs) exhibit neuroprotective properties
      and represent a potential treatment for a variety of neurodegenerative and
      neurological disorders. However, traditionally there has been a lack of
      discrimination between the different omega-3 PUFAs and effects have been broadly
      accredited to the series as a whole. Evidence for unique effects of
      eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and more recently
      docosapentaenoic acid (DPA) is growing. For example, beneficial effects in mood
      disorders have more consistently been reported in clinical trials using EPA;
      whereas, with neurodegenerative conditions such as Alzheimer's disease, the focus
      has been on DHA. DHA is quantitatively the most important omega-3 PUFA in the
      brain, and consequently the most studied, whereas the availability of high purity
      DPA preparations has been extremely limited until recently, limiting research
      into its effects. However, there is now a growing body of evidence indicating
      both independent and shared effects of EPA, DPA and DHA. The purpose of this
      review is to highlight how a detailed understanding of these effects is essential
      to improving understanding of their therapeutic potential. The review begins with
      an overview of omega-3 PUFA biochemistry and metabolism, with particular focus on
      the central nervous system (CNS), where DHA has unique and indispensable roles in
      neuronal membranes with levels preserved by multiple mechanisms. This is followed
      by a review of the different enzyme-derived anti-inflammatory mediators produced
      from EPA, DPA and DHA. Lastly, the relative protective effects of EPA, DPA and
      DHA in normal brain aging and the most common neurodegenerative disorders are
      discussed. With a greater understanding of the individual roles of EPA, DPA and
      DHA in brain health and repair it is hoped that appropriate dietary
      recommendations can be established and therapeutic interventions can be more
      targeted and refined. 

PMID- 25954196
TI  - Mechanisms of sensorineural cell damage, death and survival in the cochlea.
AB  - The majority of acquired hearing loss, including presbycusis, is caused by
      irreversible damage to the sensorineural tissues of the cochlea. This article
      reviews the intracellular mechanisms that contribute to sensorineural damage in
      the cochlea, as well as the survival signaling pathways that can provide
      endogenous protection and tissue rescue. These data have primarily been generated
      in hearing loss not directly related to age. However, there is evidence that
      similar mechanisms operate in presbycusis. Moreover, accumulation of damage from
      other causes can contribute to age-related hearing loss (ARHL). Potential
      therapeutic interventions to balance opposing but interconnected cell damage and
      survival pathways, such as antioxidants, anti-apoptotics, and pro-inflammatory
      cytokine inhibitors, are also discussed. 

PMID- 25954197
TI  - Sphingosine 1-phosphate signaling pathway in inner ear biology. New therapeutic
      strategies for hearing loss?
AB  - Hearing loss is one of the most prevalent conditions around the world, in
      particular among people over 60 years old. Thus, an increase of this affection is
      predicted as result of the aging process in our population. In this context, it
      is important to further explore the function of molecular targets involved in the
      biology of inner ear sensory cells to better individuate new candidates for
      therapeutic application. One of the main causes of deafness resides into the
      premature death of hair cells and auditory neurons. In this regard, neurotrophins
      and growth factors such as insulin like growth factor are known to be beneficial
      by favoring the survival of these cells. An elevated number of published data in
      the last 20 years have individuated sphingolipids not only as structural
      components of biological membranes but also as critical regulators of key
      biological processes, including cell survival. Ceramide, formed by catabolism of
      sphingomyelin (SM) and other complex sphingolipids, is a strong inducer of
      apoptotic pathway, whereas sphingosine 1-phosphate (S1P), generated by cleavage
      of ceramide to sphingosine and phosphorylation catalyzed by two distinct
      sphingosine kinase (SK) enzymes, stimulates cell survival. Interestingly S1P, by
      acting as intracellular mediator or as ligand of a family of five distinct S1P
      receptors (S1P1-S1P5), is a very powerful bioactive sphingolipid, capable of
      triggering also other diverse cellular responses such as cell migration,
      proliferation and differentiation, and is critically involved in the development
      and homeostasis of several organs and tissues. Although new interesting data have
      become available, the information on S1P pathway and other sphingolipids in the
      biology of the inner ear is limited. Nonetheless, there are several lines of
      evidence implicating these signaling molecules during neurogenesis in other cell
      populations. In this review, we discuss the role of S1P during inner ear
      development, also as guidance for future studies. 

PMID- 25954199
TI  - Long term follow up of patients after allogeneic stem cell transplantation and
      transfusion of HSV-TK transduced T-cells.
AB  - Allogeneic stem cell transplantation (allo-HSCT) is one of the curative
      treatments for hematologic malignancies, but is hampered by severe complications,
      such as acute or chronic graft-versus-host-disease (aGvHD; cGvHD) and infections.
      CD34-selection of stem cells reduces the risk of aGvHD, but also leads to
      increased infectious complications and relapse. Thus, we studied the safety,
      efficacy, and feasibility of transfer of gene modified donor T-cells shortly
      after allo-HSCT in two clinical trials between 2002 and 2007 and here we compare
      the results to unmodified donor leukocyte infusion (DLI). The aim of these trials
      was to provide patients with the protection of T-cells after T-cell-depleted allo
      HSCT in the matched or mismatched donor setting with an option to delete
      transduced T-cells, if severe aGvHD occurred within the trial period. Donor-T
      cells were transduced with the replication-deficient retrovirus SFCMM-3,
      expressing HSV-TK and the truncated DeltaLNGFR for selection of transduced cells.
      Transduced cells were transfused either after day +60 (matched donors) or on day
      +42 (haploidentical donors). Nine patients were included in the first trial (MHH;
      2002 until 2007), two were included in TK007 (2005-2009) and six serves as a
      control group for outcome after haploidentical transplantation without HSV-TK
      transduced DLI. Three patients developed acute GvHD, two had grade I of the skin,
      one had aGvHD on day +131 (post-HSCT; +89 post-HSV-TK DLI) grade II, which was
      successfully controlled by ganciclovir (GCV). Donor chimerism was stabilized
      after transfusion of the transduced cells in all patients treated. Functionality
      of HSV-TK gene expressing T-cells was shown by loss of bcr-able gene expression
      as well as by control of cytomegalovirus-reactivation. To date, six patients have
      relapsed and died, two after a second hematopoietic stem cell transplantation
      without T-cell depletion or administration of unmodified T-cells. Eleven patients
      (seven post-HSV-TK DLI) are alive and well to date. 

PMID- 25954200
TI  - The depressor response to intracerebroventricular hypotonic saline is sensitive
      to TRPV4 antagonist RN1734.
AB  - Several reports have shown that the periventricular region of the brain,
      including the paraventricular nucleus (PVN), is critical to sensing and
      responding to changes in plasma osmolality. Further studies also implicate the
      transient receptor potential ion channel, type V4 (TRPV4) channel in this
      homeostatic behavior. In previous work we have shown that TRPV4 ion channels
      couple to calcium-activated potassium channels in the PVN to decrease action
      potential firing frequency in response to hypotonicity. In the present study we
      investigated whether, similarly, intracerebroventricular (ICV) application of
      hypotonic solutions modulated cardiovascular parameters, and if so whether this
      was sensitive to a TRPV4 channel inhibitor. We found that ICV injection of 270
      mOsmol artificial cerebrospinal fluid (ACSF) decreased mean blood pressure, but
      not heart rate, compared to naive mice or mice injected with 300 mOsmol ACSF.
      This effect was abolished by treatment with the TRPV4 inhibitor RN1734. These
      data suggest that periventricular targets within the brain are capable of
      generating depressor action in response to TRPV4 ion channel activation.
      Potentially, in the future, the TRPV4 channel, or the TRPV4-KCa coupling
      mechanism, may serve as a therapeutic target for treatment of cardiovascular
      disease. 

PMID- 25954201
TI  - Key factors which concur to the correct therapeutic evaluation of herbal products
      in free radical-induced diseases.
AB  - For many years now the world's scientific literature has been perfused with
      articles on the therapeutic potential of natural products, the vast majority of
      which have herbal origins, as in the case of free radical-induced diseases. What
      is often overlooked is the effort of researchers who take into consideration the
      preclinical and clinical evaluation of these herbal products, in order to
      demonstrate the therapeutic efficacy and safety. The first critical issue to be
      addressed in the early stages of the preclinical studies is related to
      pharmacokinetics, which is sometimes not very favorable, of some of these
      products, which limits the bioavailability after oral intake. In this regard, it
      is worthy underlining how it is often unethical to propose the therapeutic
      efficacy of a compound on the basis of preclinical results obtained with far
      higher concentrations to those which, hopefully, could be achieved in organs and
      tissues of subjects taking these products by mouth. The most widely used approach
      to overcome the problem related to the low bioavailability involves the
      complexation of the active ingredients of herbal products with non-toxic carriers
      that facilitate the absorption and distribution. Even the induction or inhibition
      of drug metabolizing enzymes by herbal products, and the consequent variations of
      plasma concentrations of co-administered drugs, are phenomena to be carefully
      evaluated as they can give rise to side-effects. This risk is even greater when
      considering that people lack the perception of the risk arising from an over use
      of herbal products that, by their very nature, are considered risk-free. 

PMID- 25954198
TI  - Herbal hepatotoxicity in traditional and modern medicine: actual key issues and
      new encouraging steps.
AB  - Plants are natural producers of chemical substances, providing potential
      treatment of human ailments since ancient times. Some herbal chemicals in
      medicinal plants of traditional and modern medicine carry the risk of herb
      induced liver injury (HILI) with a severe or potentially lethal clinical course,
      and the requirement of a liver transplant. Discontinuation of herbal use is
      mandatory in time when HILI is first suspected as diagnosis. Although, herbal
      hepatotoxicity is of utmost clinical and regulatory importance, lack of a
      stringent causality assessment remains a major issue for patients with suspected
      HILI, while this problem is best overcome by the use of the hepatotoxicity
      specific CIOMS (Council for International Organizations of Medical Sciences)
      scale and the evaluation of unintentional reexposure test results. Sixty five
      different commonly used herbs, herbal drugs, and herbal supplements and 111
      different herbs or herbal mixtures of the traditional Chinese medicine (TCM) are
      reported causative for liver disease, with levels of causality proof that appear
      rarely conclusive. Encouraging steps in the field of herbal hepatotoxicity focus
      on introducing analytical methods that identify cases of intrinsic hepatotoxicity
      caused by pyrrolizidine alkaloids, and on omics technologies, including genomics,
      proteomics, metabolomics, and assessing circulating micro-RNA in the serum of
      some patients with intrinsic hepatotoxicity. It remains to be established whether
      these new technologies can identify idiosyncratic HILI cases. To enhance its
      globalization, herbal medicine should universally be marketed as herbal drugs
      under strict regulatory surveillance in analogy to regulatory approved chemical
      drugs, proving a positive risk/benefit profile by enforcing evidence based
      clinical trials and excellent herbal drug quality. 

PMID- 25954202
TI  - Therapeutic strategies for preventing skeletal muscle fibrosis after injury.
AB  - Skeletal muscle repair after injury includes a complex and well-coordinated
      regenerative response. However, fibrosis often manifests, leading to aberrant
      regeneration and incomplete functional recovery. Research efforts have focused on
      the use of anti-fibrotic agents aimed at reducing the fibrotic response and
      improving functional recovery. While there are a number of mediators involved in
      the development of post-injury fibrosis, TGF-beta1 is the primary pro-fibrogenic
      growth factor and several agents that inactivate TGF-beta1 signaling cascade have
      emerged as promising anti-fibrotic therapies. A number of these agents are FDA
      approved for other conditions, clearing the way for rapid translation into
      clinical treatment. In this article, we provide an overview of muscle's host
      response to injury with special emphasis on the cellular and non-cellular
      mediators involved in the development of fibrosis. This article also reviews the
      findings of several pre-clinical studies that have utilized anti-fibrotic agents
      to improve muscle healing following most common forms of muscle injuries.
      Although some studies have shown positive results with anti-fibrotic treatment,
      others have indicated adverse outcomes. Some concerns and questions regarding the
      clinical potential of these anti-fibrotic agents have also been presented. 

PMID- 25954203
TI  - Role of bone morphogenetic protein-7 in renal fibrosis.
AB  - Renal fibrosis is final common pathway of end stage renal disease. Irrespective
      of the primary cause, renal fibrogenesis is a dynamic process which involves a
      large network of cellular and molecular interaction, including pro-inflammatory
      cell infiltration and activation, matrix-producing cell accumulation and
      activation, and secretion of profibrogenic factors that modulate extracellular
      matrix (ECM) formation and cell-cell interaction. Bone morphogenetic protein-7 is
      a protein of the TGF-beta super family and increasingly regarded as a
      counteracting molecule against TGF-beta. A large variety of evidence shows an
      anti-fibrotic role of BMP-7 in chronic kidney disease, and this effect is largely
      mediated via counterbalancing the profibrotic effect of TGF-beta. Besides, BMP-7
      reduced ECM formation by inactivating matrix-producing cells and promoting
      mesenchymal-to-epithelial transition (MET). BMP-7 also increased ECM degradation.
      Despite these observations, the anti-fibrotic effect of BMP-7 is still
      controversial such that fine regulation of BMP-7 expression in vivo might be a
      great challenge for its ultimate clinical application. 

PMID- 25954204
TI  - Role of non-classical renin-angiotensin system axis in renal fibrosis.
AB  - The renin-angiotensin system (RAS) is a major regulator of renal fibrosis.
      Besides the classical renin/Angiotensin-converting enzyme (ACE)/angiotensin II
      (Ang II)/AT1 and AT2 axis, multiple new axes have been recently described. The
      new members have added new dimensions to RAS, including the ACE2/Ang(1-7)/Mas
      receptor axis, the prorenin/(pro)renin receptor(PRR)/intracelluar pathway axis,
      and the Angiotensin A (Ang A), alamandine-Mas-related G protein coupled receptor
      D(MrgD) axis. This review summarized recent studies regarding role of the non
      classical RAS axis in renal fibrosis, and its possible implications to the
      intervention of progression of chronic kidney disease. 

PMID- 25954205
TI  - Biomimetic extracellular matrix mediated somatic stem cell differentiation:
      applications in dental pulp tissue regeneration.
AB  - Dental caries is one of the most widely prevalent infectious diseases in the
      world. It affects more than half of the world's population. The current treatment
      for necrotic dental pulp tissue arising from dental caries is root canal therapy.
      This treatment results in loss of tooth sensitivity and vitality making it prone
      for secondary infections. Over the past decade, several tissue-engineering
      approaches have attempted regeneration of the dental pulp tissue. Although
      several studies have highlighted the potential of dental stem cells, none have
      transitioned into a clinical setting owing to limited availability of dental stem
      cells and the need for growth factor delivery systems. Our strategy is to utilize
      the intact ECM of pulp cells to drive lineage specific differentiation of bone
      marrow derived mesenchymal stem cells. From a clinical perspective, pulp ECM
      scaffolds can be generated using cell lines and patient specific somatic stem
      cells can be used for regeneration. Our published results have shown the
      feasibility of using pulp ECM scaffolds for odontogenic differentiation of non
      dental mesenchymal cells. This focused review discusses the issues surrounding
      dental pulp tissue regeneration and the potential of our strategy to overcome
      these issues. 

PMID- 25954206
TI  - Key enzymes and proteins of crop insects as candidate for RNAi based gene
      silencing.
AB  - RNA interference (RNAi) is a mechanism of homology dependent gene silencing
      present in plants and animals. It operates through 21-24 nucleotides small RNAs
      which are processed through a set of core enzymatic machinery that involves Dicer
      and Argonaute proteins. In recent past, the technology has been well appreciated
      toward the control of plant pathogens and insects through suppression of key
      genes/proteins of infecting organisms. The genes encoding key enzymes/proteins
      with the great potential for developing an effective insect control by RNAi
      approach are actylcholinesterase, cytochrome P450 enzymes, amino peptidase N,
      allatostatin, allatotropin, tryptophan oxygenase, arginine kinase, vacuolar
      ATPase, chitin synthase, glutathione-S-transferase, catalase, trehalose phosphate
      synthase, vitellogenin, hydroxy-3-methylglutaryl coenzyme A reductase, and
      hormone receptor genes. Through various studies, it is demonstrated that RNAi is
      a reliable molecular tool which offers great promises in meeting the challenges
      imposed by crop insects with careful selection of key enzymes/proteins.
      Utilization of RNAi tool to target some of these key proteins of crop insects
      through various approaches is described here. The major challenges of RNAi based
      insect control such as identifying potential targets, delivery methods of
      silencing trigger, off target effects, and complexity of insect biology are very
      well illustrated. Further, required efforts to address these challenges are also
      discussed. 

PMID- 25954207
TI  - Exercise ameliorates high fat diet induced cardiac dysfunction by increasing
      interleukin 10.
AB  - Increasing evidence suggests that a sedentary lifestyle and a high fat diet (HFD)
      leads to cardiomyopathy. Moderate exercise ameliorates cardiac dysfunction,
      however underlying molecular mechanisms are poorly understood. Increased
      inflammation due to induction of pro-inflammatory cytokine such as tumor necrosis
      factor-alpha (TNF-alpha) and attenuation of anti-inflammatory cytokine such as
      interleukin 10 (IL-10) contributes to cardiac dysfunction in obese and diabetics.
      We hypothesized that exercise training ameliorates HFD- induced cardiac
      dysfunction by mitigating obesity and inflammation through upregulation of IL-10
      and downregulation of TNF-alpha. To test this hypothesis, 8 week old, female
      C57BL/6J mice were fed with HFD and exercised (swimming 1 h/day for 5 days/week
      for 8 weeks). The four treatment groups: normal diet (ND), HFD, HFD + exercise
      (HFD + Ex) and ND + Ex were analyzed for mean body weight, blood glucose level,
      TNF-alpha, IL-10, cardiac fibrosis by Masson Trichrome, and cardiac dysfunction
      by echocardiography. Mean body weights were increased in HFD but comparatively
      less in HFD + Ex. The level of TNF-alpha was elevated and IL-10 was downregulated
      in HFD but ameliorated in HFD + Ex. Cardiac fibrosis increased in HFD and was
      attenuated by exercise in the HFD + Ex group. The percentage ejection fraction
      and fractional shortening were decreased in HFD but comparatively increased in
      HFD + Ex. There was no difference between ND and ND + Ex for the above parameters
      except an increase in IL-10 level following exercise. Based on these results, we
      conclude that exercise mitigates HFD- induced cardiomyopathy by decreasing
      obesity, inducing IL-10, and reducing TNF-alpha in mice. 

PMID- 25954209
TI  - Association between Unmet Needs and Clinical Status in Patients with First
      Episode of Schizophrenia in Chile.
AB  - BACKGROUND: Schizophrenia is a severe mental disorder involving needs in several
      matters that are often not covered. A need is defined as a gap between the ideal
      state and the current state of a patient about a specific topic. AIM: To describe
      needs in patients with first episode of schizophrenia at the start of treatment
      and to describe associated clinical factors. METHODS: Observational descriptive
      cross-sectional design. Patients were over 15 years old, with first episode
      schizophrenia, and admitted to treatment in the public health system from six
      districts in two cities of Chile, between 2005 and 2006. Sociodemographic data,
      clinical evaluations of current psychosis based on the Positive and Negative
      Syndrome Scale (PANSS), and the time of untreated psychosis were obtained. A
      clinical interview was carried out followed by the Camberwell Assessment of Need.
      RESULTS: Twenty-nine patients were evaluated, 79.3% male, mean age 21.9 years
      old. The areas with more needs reported were; psychotic symptoms with 65.5% of
      sample, 21.1% of which reported it unmet; and daytime activities, where 44.8% of
      patients reported a need, 61.54% of them as unmet. The percentage of unmet needs
      correlated with PANSS score (r = 0.55; p = 0.003), and with time of positive
      symptoms prior to diagnosis (r = 0.416; p = 0.03). DISCUSSION: Needs assessment
      in schizophrenia is necessary. It may affect its clinical course, be relevant in
      its management, and help monitor recovery. Defining the main needs in people with
      first episode schizophrenia and associated factors allows for a better design of
      treatment strategies in order to obtain better therapeutic results and recovery.

PMID- 25954210
TI  - Salivary oxytocin concentrations in seven boys with autism spectrum disorder
      received massage from their mothers: a pilot study.
AB  - Seven male children with autism spectrum disorder (ASD), aged 8-12 years,
      attending special education classrooms for ASD and disabled children, were
      assigned to receive touch therapy. Their mothers were instructed to provide
      gentle touch in the massage style of the International Liddle Kidz Association.
      The mothers gave massages to their child for 20 min every day over a period of 3
      months, followed by no massage for 4 months. To assess the biological effects of
      such touch therapy, saliva was collected before and 20 min after a single session
      of massage for 20 min from the children and mothers every 3 weeks during the
      massage period and every 4 weeks during the non-massage period, when they visited
      a community meeting room. Salivary oxytocin levels were measured using an enzyme
      immunoassay kit. During the period of massage therapy, the children and mothers
      exhibited higher oxytocin concentrations compared to those during the non-massage
      period. The changes in oxytocin levels before and after a single massage session
      were not significantly changed in children and mothers. The results suggested
      that the ASD children (massage receivers) and their mothers (massage givers) show
      touch therapy-dependent changes in salivary oxytocin concentrations. 

PMID- 25954208
TI  - Neuropsychology, autobiographical memory, and hippocampal volume in "younger" and
      "older" patients with chronic schizophrenia.
AB  - Despite a wide range of studies on neuropsychology in schizophrenia,
      autobiographical memory (AM) has been scarcely investigated in these patients.
      Hence, less is known about AM in older patients and hippocampal contribution to
      autobiographical memories of varying remoteness. Therefore, we investigated
      hippocampal volume and AM along with important neuropsychological domains in
      patients with chronic schizophrenia and the respective relationships between
      these parameters. We compared 25 older patients with chronic schizophrenia to 23
      younger patients and an older healthy control group (N = 21) with respect to AM,
      additional neuropsychological parameters, and hippocampal volume. Personal
      episodic and semantic memory was investigated using a semi-structured interview.
      Additional neuropsychological parameters were assessed by using a battery of
      standard neuropsychological tests. Structural magnetic resonance imaging data
      were analyzed with an automated region-of-interest procedure. While hippocampal
      volume reduction and neuropsychological impairment were more pronounced in the
      older than in the younger patients, both groups showed equivalent reduced AM
      performance for recent personal episodes. In the patient group, significant
      correlations between left hippocampal volume and recent autobiographical episodes
      as well as personal semantic memories arose. Verbal memory and working memory
      were significantly correlated with right hippocampal volume; executive functions,
      however, were associated with bilateral hippocampal volumes. These findings
      underline the complexity of AM and its impairments in the course of schizophrenia
      in comparison to rather progressive neuropsychological deficits and address the
      importance of hippocampal contribution. 

PMID- 25954211
TI  - By their words ye shall know them: Evidence of genetic selection against general
      intelligence and concurrent environmental enrichment in vocabulary usage since
      the mid 19th century.
AB  - It has been theorized that declines in general intelligence (g) due to genetic
      selection stemming from the inverse association between completed fertility and
      IQ and the Flynn effect co-occur, with the effects of the latter being
      concentrated on less heritable non-g sources of intelligence variance. Evidence
      for this comes from the observation that 19th century populations were more
      intellectually productive, and also exhibited faster simple reaction times than
      modern ones, suggesting greater information-processing ability and therefore
      higher g. This co-occurrence model is tested via examination of historical
      changes in the utilization frequencies of words from the highly g-loaded WORDSUM
      test across 5.9 million texts spanning the period 1850-2005. Consistent with
      predictions, words with higher difficulties (delta parameters from Item Response
      Theory) and stronger negative correlations between pass rates and completed
      fertility declined in use over time whereas less difficult and less strongly
      selected words, increased in use over time, consistent with a Flynn effect
      stemming in part from the vocabulary enriching effects of increases in population
      literacy. These findings persisted when explicitly controlled for word age,
      changing literacy rates and temporal autocorrelation. These trends constitute
      compelling evidence for the co-occurrence model. 

PMID- 25954212
TI  - Cognition from life: the two modes of cognition that underlie moral behavior.
AB  - We argue that the capacity to live life to the benefit of self and others
      originates in the defining properties of life. These lead to two modes of
      cognition; the coping mode that is preoccupied with the satisfaction of pressing
      needs and the co-creation mode that aims at the realization of a world where
      pressing needs occur less frequently. We have used the Rule of Conservative
      Changes - stating that new functions can only scaffold on evolutionary older, yet
      highly stable functions - to predict that the interplay of these two modes define
      a number of core functions in psychology associated with moral behavior. We
      explore this prediction with five examples reflecting different theoretical
      approaches to human cognition and action selection. We conclude the paper with
      the observation that science is currently dominated by the coping mode and that
      the benefits of the co-creation mode may be necessary to generate realistic
      prospects for a modern synthesis in the sciences of the mind. 

PMID- 25954214
TI  - The not-always-uniquely-predictive power of an evolutionary approach to
      understanding our not-so-computational nature.

PMID- 25954213
TI  - Heritability of decisions and outcomes of public goods games.
AB  - Prosociality is one of the most distinctive features of human beings but there
      are individual differences in cooperative behavior. Employing the twin method, we
      examined the heritability of cooperativeness and its outcomes on public goods
      games using a strategy method. In two experiments (Study 1 and Study 2), twin
      participants were asked to indicate (1) how much they would contribute to a group
      when they did not know how much the other group members were contributing, and
      (2) how much they would contribute if they knew the contributions of others.
      Overall, the heritability estimates were relatively small for each type of
      decision, but heritability was greater when participants knew that the others had
      made larger contributions. Using registered decisions in Study 2, we conducted
      seven Monte Carlo simulations to examine genetic and environmental influences on
      the expected game payoffs. For the simulated one-shot game, the heritability
      estimates were small, comparable to those of game decisions. For the simulated
      iterated games, we found that the genetic influences first decreased, then
      increased as the numbers of iterations grew. The implication for the evolution of
      individual differences in prosociality is discussed. 

PMID- 25954215
TI  - Alliance: a common factor of psychotherapy modeled by structural theory.
AB  - There is broad consensus that the therapeutic alliance constitutes a core common
      factor for all modalities of psychotherapy. Meta-analyses corroborated that
      alliance, as it emerges from therapeutic process, is a significant predictor of
      therapy outcome. Psychotherapy process is traditionally described and explored
      using two categorically different approaches, the experiential (first-person)
      perspective and the behavioral (third-person) perspective. We propose to add to
      this duality a third, structural approach. Dynamical systems theory and
      synergetics on the one hand and enactivist theory on the other together can
      provide this structural approach, which contributes in specific ways to a
      clarification of the alliance factor. Systems theory offers concepts and tools
      for the modeling of the individual self and, building on this, of alliance
      processes. In the enactive perspective, the self is conceived as a socially
      enacted autonomous system that strives to maintain identity by observing a two
      fold goal: to exist as an individual self in its own right (distinction) while
      also being open to others (participation). Using this conceptualization, we
      formalized the therapeutic alliance as a phase space whose potential minima
      (attractors) can be shifted by the therapist to approximate therapy goals. This
      mathematical formalization is derived from probability theory and synergetics. We
      draw the conclusion that structural theory provides powerful tools for the
      modeling of how therapeutic change is staged by the formation, utilization, and
      dissolution of the therapeutic alliance. In addition, we point out novel testable
      hypotheses and future applications. 

PMID- 25954216
TI  - Strategic differentiation and integration of genomic-level heritabilities
      facilitate individual differences in preparedness and plasticity of human life
      history.
AB  - Life history (LH) strategies refer to the pattern of allocations of bioenergetic
      and material resources into different domains of fitness. While LH is known to
      have moderate to high population-level heritability in humans, both at the level
      of the high-order factor (Super-K) and the lower-order factors (K, Covitality,
      and the General Factor of Personality), several important questions remain
      unexplored. Here, we apply the Continuous Parameter Estimation Model to measure
      individual genomic-level heritabilities (termed transmissibilities). These
      transmissibility values were computed for the latent hierarchical structure and
      developmental dynamics of LH strategy, and demonstrate; (1) moderate to high
      heritability of factor loadings of Super-K on its lower-order factors, evidencing
      biological preparedness, genetic accommodation, and the gene-culture coevolution
      of biased epigenetic rules of development; (2) moderate to high heritability of
      the magnitudes of the effect of the higher-order factors upon their loadings on
      their constituent factors, evidencing genetic constraints upon phenotypic
      plasticity; and (3) that heritability of the LH factors, their factor loadings,
      and the magnitudes of the correlations among factors, are weaker among
      individuals with slower LH speeds. The results were obtained from an American
      sample of 316 monozygotic (MZ) and 274 dizygotic (DZ) twin dyads and a Swedish
      sample of 863 MZ and 475 DZ twin dyads, and indicate that inter-individual
      variation in transmissibility is a function of individual socioecological
      selection pressures. Our novel technique, opens new avenues for analyzing complex
      interactions among heritable traits inaccessible to standard structural equation
      methods. 

PMID- 25954217
TI  - Cross-modal associations between materic painting and classical Spanish music.
AB  - The study analyses the existence of cross-modal associations in the general
      population between a series of paintings and a series of clips of classical
      (guitar) music. Because of the complexity of the stimuli, the study differs from
      previous analyses conducted on the association between visual and auditory
      stimuli, which predominantly analyzed single tones and colors by means of
      psychophysical methods and forced choice responses. More recently, the relation
      between music and shape has been analyzed in terms of music visualization, or
      relatively to the role played by emotion in the association, and free response
      paradigms have also been accepted. In our study, in order to investigate what
      attributes may be responsible for the phenomenon of the association between
      visual and auditory stimuli, the clip/painting association was tested in two
      experiments: the first used the semantic differential on a unidimensional rating
      scale of adjectives; the second employed a specific methodology based on
      subjective perceptual judgments in first person account. Because of the
      complexity of the stimuli, it was decided to have the maximum possible uniformity
      of style, composition and musical color. The results show that multisensory
      features expressed by adjectives such as "quick," "agitated," and "strong," and
      their antonyms "slow," "calm," and "weak" characterized both the visual and
      auditory stimuli, and that they may have had a role in the associations. The
      results also suggest that the main perceptual features responsible for the
      clip/painting associations were hue, lightness, timbre, and musical tempo.
      Contrary to what was expected, the musical mode usually related to feelings of
      happiness (major mode), or to feelings of sadness (minor mode), and spatial
      orientation (vertical and horizontal) did not play a significant role in the
      association. The consistency of the associations was shown when evaluated on the
      whole sample, and after considering the different backgrounds and expertise of
      the subjects. No substantial difference was found between expert and non-expert
      subjects. The methods used in the experiment (semantic differential and
      subjective judgements in first person account) corroborated the interpretation of
      the results as associations due to patterns of qualitative similarity present in
      stimuli of different sensory modalities and experienced as such by the subjects.
      The main result of the study consists in showing the existence of cross-modal
      associations between highly complex stimuli; furthermore, the second experiment
      employed a specific methodology based on subjective perceptual judgments. 

PMID- 25954218
TI  - The impact of cognitive load on operatic singers' timing performance.
AB  - In the present paper, we report the results of an empirical study on the effects
      of cognitive load on operatic singing. The main aim of the study was to
      investigate to what extent a working memory task affected the timing of operatic
      singers' performance. Thereby, we focused on singers' tendency to speed up, or
      slow down their performance of musical phrases and pauses. Twelve professional
      operatic singers were asked to perform an operatic aria three times; once without
      an additional working memory task, once with a concurrent working memory task
      (counting shapes on a computer screen), and once with a relatively more difficult
      working memory task (more shapes to be counted appearing one after another). The
      results show that, in general, singers speeded up their performance under
      heightened cognitive load. Interestingly, this effect was more pronounced in
      pauses-more in particular longer pauses-compared to musical phrases. We discuss
      the role of sensorimotor control and feedback processes in musical timing to
      explain these findings. 

PMID- 25954219
TI  - Investigating the shape bias in typically developing children and children with
      autism spectrum disorders.
AB  - Young typically developing (TD) children have been observed to utilize word
      learning strategies such as the noun bias and shape bias; these improve their
      efficiency in acquiring and categorizing novel terms. Children using the shape
      bias extend object labels to new objects of the same shape; thus, the shape bias
      prompts the categorization of object words based on the global characteristic of
      shape over local, discrete details. Individuals with autism spectrum disorders
      (ASDs) frequently attend to minor details of objects rather than their global
      structure. Therefore, children with ASD may not use shape bias to acquire new
      words. Previous research with children with ASD has provided evidence that they
      parallel TD children in showing a noun bias, but not a shape bias (Tek et al.,
      2008). However, this sample was small and individual and item differences were
      not investigated in depth. In an extension of Tek et al. (2008) with twice the
      sample size and a wider developmental timespan, we tested 32 children with ASD
      and 35 TD children in a longitudinal study across 20 months using the intermodal
      preferential looking paradigm. Children saw five triads of novel objects (target,
      shape-match, color-match) in both NoName and Name trials; those who looked longer
      at the shape-match during the Name trials than the NoName trials demonstrated a
      shape bias. The TD group showed a significant shape bias at all visits, beginning
      at 20 months of age while the language-matched ASD group did not show a
      significant shape bias at any visit. Within the ASD group, though, some children
      did show a shape bias; these children had larger vocabularies concurrently and
      longitudinally. Degree of shape bias elicitation varied by item, but did not seem
      related to perceptual complexity. We conclude that shape does not appear to be an
      organizing factor for word learning by children with ASD. 

PMID- 25954220
TI  - Impact of feature saliency on visual category learning.
AB  - People have to sort numerous objects into a large number of meaningful categories
      while operating in varying contexts. This requires identifying the visual
      features that best predict the 'essence' of objects (e.g., edibility), rather
      than categorizing objects based on the most salient features in a given context.
      To gain this capacity, visual category learning (VCL) relies on multiple
      cognitive processes. These may include unsupervised statistical learning, that
      requires observing multiple objects for learning the statistics of their
      features. Other learning processes enable incorporating different sources of
      supervisory information, alongside the visual features of the categorized
      objects, from which the categorical relations between few objects can be deduced.
      These deductions enable inferring that objects from the same category may differ
      from one another in some high-saliency feature dimensions, whereas lower-saliency
      feature dimensions can best differentiate objects from distinct categories. Here
      I illustrate how feature saliency affects VCL, by also discussing kinds of
      supervisory information enabling reflective categorization. Arguably, principles
      debated here are often being ignored in categorization studies. 

PMID- 25954221
TI  - Strengths-based positive psychology interventions: a randomized placebo
      controlled online trial on long-term effects for a signature strengths- vs. a
      lesser strengths-intervention.
AB  - Recent years have seen an increasing interest in research in positive psychology
      interventions. There is broad evidence for their effectiveness in increasing well
      being and ameliorating depression. Intentional activities that focus on those
      character strengths, which are most typical for a person (i.e., signature
      strengths, SS) and encourage their usage in a new way have been identified as
      highly effective. The current study aims at comparing an intervention aimed at
      using SS with one on using individual low scoring (or lesser) strengths in a
      randomized placebo-controlled trial. A total of 375 adults were randomly assigned
      to one of the two intervention conditions [i.e., using five signature vs. five
      lesser strengths (LS) in a new way] or a placebo control condition (i.e., early
      memories). We measured happiness and depressive symptoms at five time points
      (i.e., pre- and post-test, 1-, 3-, and 6-months follow-ups) and character
      strengths at pre-test. The main findings are that (1) there were increases in
      happiness for up to 3 months and decreases in depressive symptoms in the short
      term in both intervention conditions; (2) participants found working with
      strengths equally rewarding (enjoyment and benefit) in both conditions; (3) those
      participants that reported generally higher levels of strengths benefitted more
      from working on LS rather than SS and those with comparatively lower levels of
      strengths tended to benefit more from working on SS; and (4) deviations from an
      average profile derived from a large sample of German-speakers completing the
      Values-in-Action Inventory of Strengths were associated with greater benefit from
      the interventions in the SS-condition. We conclude that working on character
      strengths is effective for increasing happiness and discuss how these
      interventions could be tailored to the individual for promoting their
      effectiveness. 

PMID- 25954222
TI  - Mapping strengths into virtues: the relation of the 24 VIA-strengths to six
      ubiquitous virtues.
AB  - The Values-in-Action-classification distinguishes six core virtues and 24
      strengths. As the assignment of the strengths to the virtues was done on
      theoretical grounds it still needs empirical verification. As an alternative to
      factor analytic investigations the present study utilizes expert judgments. In a
      pilot study the conceptual overlap among five sources of knowledge (strength's
      name including synonyms, short definitions, brief descriptions, longer
      theoretical elaborations, and item content) about a particular strength was
      examined. The results show that the five sources converged quite well, with the
      short definitions and the items being slightly different from the other. All
      strengths exceeded a cut-off value but the convergence was much better for some
      strengths (e.g., zest) than for others (e.g., perspective). In the main study 70
      experts (from psychology, philosophy, theology, etc.) and 41 laypersons rated how
      prototypical the strengths are for each of the six virtues. The results showed
      that 10 were very good markers for their virtues, nine were good markers, four
      were acceptable markers, and only one strength failed to reach the cut-off score
      for its assigned virtue. However, strengths were often markers for two or even
      three virtues, and occasionally they marked the other virtue more strongly than
      the one they were assigned to. The virtue prototypicality ratings were slightly
      positively correlated with higher coefficients being found for justice and
      humanity. A factor analysis of the 24 strengths across the ratings yielded the
      six factors with an only slightly different composition of strengths and double
      loadings. It is proposed to adjust either the classification (by reassigning
      strengths and by allowing strengths to be subsumed under more than one virtue) or
      to change the definition of certain strengths so that they only exemplify one
      virtue. The results are discussed in the context of factor analytic attempts to
      verify the structural model. 

PMID- 25954224
TI  - Validity of personality measurement in adults with anxiety disorders:
      psychometric properties of the Spanish NEO-FFI-R using Rasch analyses.
AB  - The aim of this study was to analyse the psychometric properties of the Spanish
      NEO Five Factor Inventory-Revised (NEO-FFI-R) using Rasch analyses, in order to
      test its rating scale functioning, the reliability of scores, internal structure,
      and differential item functioning (DIF) by gender in a psychiatric sample. The
      NEO-FFI-R responses of 433 Spanish adults (154 males) with an anxiety disorder as
      primary diagnosis were analysed using the Rasch model for rating scales. Two
      intermediate categories of response ('neutral' and 'agree') malfunctioned in the
      Neuroticism and Conscientiousness scales. In addition, model reliabilities were
      lower than expected in Agreeableness and Neuroticism, and the item fit values
      indicated each scale had items that did not achieve moderate to high
      discrimination on its dimension, particularly in the Agreeableness scale.
      Concerning unidimensionality, the five NEO-FFI-R scales showed large first
      components of unexplained variance. Finally, DIF by gender was detected in many
      items. The results suggest that the scores of the Spanish NEO-FFI-R are
      unreliable in psychiatric samples and cannot be generalized between males and
      females, especially in the Openness, Conscientiousness, and Agreeableness scales.
      Future directions for testing and refinement should be developed before the NEO
      FFI-R can be used reliably in clinical samples. 

PMID- 25954225
TI  - Effects of question formats on causal judgments and model evaluation.
AB  - Evaluation of causal reasoning models depends on how well the subjects' causal
      beliefs are assessed. Elicitation of causal beliefs is determined by the
      experimental questions put to subjects. We examined the impact of question
      formats commonly used in causal reasoning research on participant's responses.
      The results of our experiment (Study 1) demonstrate that both the mean and
      homogeneity of the responses can be substantially influenced by the type of
      question (structure induction versus strength estimation versus prediction).
      Study 2A demonstrates that subjects' responses to a question requiring them to
      predict the effect of a candidate cause can be significantly lower and more
      heterogeneous than their responses to a question asking them to diagnose a cause
      when given an effect. Study 2B suggests that diagnostic reasoning can strongly
      benefit from cues relating to temporal precedence of the cause in the question.
      Finally, we evaluated 16 variations of recent computational models and found the
      model fitting was substantially influenced by the type of questions. Our results
      show that future research in causal reasoning should place a high priority on
      disentangling the effects of question formats from the effects of experimental
      manipulations, because that will enable comparisons between models of causal
      reasoning uncontaminated by method artifact. 

PMID- 25954223
TI  - A theory of social thermoregulation in human primates.
AB  - Beyond breathing, the regulation of body temperature-thermoregulation-is one of
      the most pressing concerns for many animals. A dysregulated body temperature has
      dire consequences for survival and development. Despite the high frequency of
      social thermoregulation occurring across many species, little is known about the
      role of social thermoregulation in human (social) psychological functioning. We
      outline a theory of social thermoregulation and reconsider earlier research on
      people's expectations of their social world (i.e., attachment) and their
      prediction of the social world. We provide support and outline a research agenda
      that includes consequences for individual variation in self-regulatory strategies
      and capabilities. In our paper, we discuss physiological, neural, and social
      processes surrounding thermoregulation. Emphasizing social thermoregulation in
      particular, we appeal to the economy of action principle and the hierarchical
      organization of human thermoregulatory systems. We close with future directions
      of a crucial aspect of human functioning: the social regulation of body
      temperature. 

PMID- 25954226
TI  - Ahead of others in the authorship order: names with middle initials appear
      earlier in author lists of academic articles in psychology.
AB  - Middle name initials are often used by people in contexts where intellectual
      performance matters. Given this association, middle initials in people's names
      indicate intellectual capacity and performance (Van Tilburg and Igou, 2014). In
      the current research, we examined whether middle initials are associated with a
      typical academic indicator of intellectual performance: authorship order of
      journal articles. In psychology, authorship early in the author list of an
      article should correspond with greater contribution to this intellectual endeavor
      compared to authorship appearing later in the author list. Given that middle
      initials indicate intellectual capacity and performance, we investigated whether
      there would be a positive relationship between middle initials in author names
      and early (vs. late) appearance of names in author lists of academic journal
      articles in psychology. In two studies, we examined the relationship between
      amount of authors' middle initials and authorship order. Study 1 used a sample of
      678 articles from social psychology journals published in the years 2006 and
      2007. Study 2 used a sample of 696 articles from journals of multiple sub
      disciplines in psychology published in the years from 1970 to 2013. Middle
      initials in author names were overrepresented early (vs. late) in author lists.
      We discuss implications of our findings for academic decisions on authorship
      orders, potential avenues of further investigation, and applications. 

PMID- 25954227
TI  - Do positive relations with patients play a protective role for healthcare
      employees? Effects of patients' gratitude and support on nurses' burnout.
AB  - BACKGROUND: A growing number of studies reveal that there are significant
      associations between a patient's perception of quality of care and a health
      professional's perceived quality of work life. Previous studies focused on the
      patients or on the workers. Alternatively, they center the discussion on either
      the negative or the positive effects, both on patients and care workers. This
      research work focuses on the positive relationship with patients-a possible
      resource for care workers. METHOD: Study 1: A CFA was conducted to test the
      factorial structure and the tenure of the Italian version for patients of the
      Customer-initiated Support scale. Study 2: Using a multi-group path analysis, the
      effects of work characteristics and of the relationship with patients on burnout
      were tested in two different contexts: emergency and oncology ward. RESULTS:
      Study 1: The one-factor instrument shows good reliability, convergent, and
      divergent validity. Study 2: for oncology nurses cognitive demands, job autonomy,
      and support from patients have direct effects on emotional exhaustion and job
      autonomy; interactions between cognitive demands and patients' support have an
      effect on depersonalization. For emergency nurses cognitive demands and
      interactions between job autonomy and support from patients have effects on
      emotional exhaustion; job autonomy, patients support and gratitude have direct
      effects on personal accomplishment. CONCLUSIONS: RESULTS confirm expectations
      about the role of patients' support and gratitude in reducing nurses' burnout,
      with differences in the two contexts: emergency nurses show higher burnout and
      lower perception of positive relationship with patients, but present more intense
      protective effects of the interaction between job autonomy and support/gratitude.
      Suggestions can be offered to managers in developing interventions to promote
      "healthy organization" culture that consider jointly employees and patients'
      needs.

PMID- 25954228
TI  - Is the preference of natural versus man-made scenes driven by bottom-up
      processing of the visual features of nature?
AB  - Previous research has shown that viewing images of nature scenes can have a
      beneficial effect on memory, attention, and mood. In this study, we aimed to
      determine whether the preference of natural versus man-made scenes is driven by
      bottom-up processing of the low-level visual features of nature. We used
      participants' ratings of perceived naturalness as well as esthetic preference for
      307 images with varied natural and urban content. We then quantified 10 low-level
      image features for each image (a combination of spatial and color properties).
      These features were used to predict esthetic preference in the images, as well as
      to decompose perceived naturalness to its predictable (modeled by the low-level
      visual features) and non-modeled aspects. Interactions of these separate aspects
      of naturalness with the time it took to make a preference judgment showed that
      naturalness based on low-level features related more to preference when the
      judgment was faster (bottom-up). On the other hand, perceived naturalness that
      was not modeled by low-level features was related more to preference when the
      judgment was slower. A quadratic discriminant classification analysis showed how
      relevant each aspect of naturalness (modeled and non-modeled) was to predicting
      preference ratings, as well as the image features on their own. Finally, we
      compared the effect of color-related and structure-related modeled naturalness,
      and the remaining unmodeled naturalness in predicting esthetic preference. In
      summary, bottom-up (color and spatial) properties of natural images captured by
      our features and the non-modeled naturalness are important to esthetic judgments
      of natural and man-made scenes, with each predicting unique variance. 

PMID- 25954229
TI  - From clinical reasoning to effective clinical decision making-new training
      methods.

PMID- 25954230
TI  - A cautionary note on the use of the Analysis of Covariance (ANCOVA) in
      classification designs with and without within-subject factors.
AB  - A number of statistical textbooks recommend using an analysis of covariance
      (ANCOVA) to control for the effects of extraneous factors that might influence
      the dependent measure of interest. However, it is not generally recognized that
      serious problems of interpretation can arise when the design contains comparisons
      of participants sampled from different populations (classification designs).
      Designs that include a comparison of younger and older adults, or a comparison of
      musicians and non-musicians are examples of classification designs. In such
      cases, estimates of differences among groups can be contaminated by differences
      in the covariate population means across groups. A second problem of
      interpretation will arise if the experimenter fails to center the covariate
      measures (subtracting the mean covariate score from each covariate score)
      whenever the design contains within-subject factors. Unless the covariate
      measures on the participants are centered, estimates of within-subject factors
      are distorted, and significant increases in Type I error rates, and/or losses in
      power can occur when evaluating the effects of within-subject factors. This
      paper: (1) alerts potential users of ANCOVA of the need to center the covariate
      measures when the design contains within-subject factors, and (2) indicates how
      they can avoid biases when one cannot assume that the expected value of the
      covariate measure is the same for all of the groups in a classification design. 

PMID- 25954232
TI  - Social anxiety under load: the effects of perceptual load in processing emotional
      faces.
AB  - Previous studies in the social anxiety arena have shown an impaired attentional
      control system, similar to that found in trait anxiety. However, the effect of
      task demands on social anxiety in socially threatening stimuli, such as angry
      faces, remains unseen. In the present study, 54 university students scoring high
      and low in the Social Interaction and Performance Anxiety and Avoidance Scale
      (SIPAAS) questionnaire, participated in a target letter discrimination task while
      task-irrelevant face stimuli (angry, disgust, happy, and neutral) were
      simultaneously presented. The results showed that high (compared to low) socially
      anxious individuals were more prone to distraction by task-irrelevant stimuli,
      particularly under high perceptual load conditions. More importantly, for such
      individuals, the accuracy proportions for angry faces significantly differed
      between the low and high perceptual load conditions, which is discussed in light
      of current evolutionary models of social anxiety. 

PMID- 25954231
TI  - Observing the determinants of the psychotherapeutic process in depressive
      disorders. A clinical case study within a psychodynamic approach.
AB  - This paper focuses on the relationship between depressive disorders, personality
      configurations, and mental functioning. A one-year treatment of a young man with
      the diagnosis of Depression is presented: the clinical and empirical points of
      view are described in depth through an assessment at the beginning and at one
      year after of an oriented psychodynamic psychotherapy. SCID I and II and HAMRS
      were administered to the patient in assessment phase. In the same phase he filled
      in BDI-II, and DEQ; the psychotherapist completed SWAP-200. These clinician
      instruments were used again after 1 year of the treatment. The PDM point of view
      is also presented. All sessions are audiotaped: 12 verbatim transcripts were
      coded with the Defense Mechanisms Rating Scale and CCRT. The results show a
      decrease in depressive symptoms, a change in some personality configurations, but
      a substantial invariance of the introjective profile, and a modification in
      mental functioning. 

PMID- 25954233
TI  - Adults with sensorimotor disorders: enhanced physiological and psychological
      development following specific sensorimotor training.
AB  - The aim of the study was to investigate, for the first time, if it is possible to
      integrate primary reflexes in adults with sensorimotor disorders through
      sensorimotor therapy (SMT). Participants consisted of 14 adults, one man and 13
      women, with an average age of 35 years who completed a SMT program over 3 years.
      They were compared with a reference group of 100 youngsters spanning from 11 to
      17 years. Procedures were the same for both youngsters and adults including
      regular visits to a therapist and training ~15 min each day at home throughout
      therapy. Assessments of sensorimotor abilities were made before and after the
      therapy. Results showed significant improvements on all measurements with regard
      to treatment for both age groups and the main picture indicated small differences
      between age groups. After therapy adults were better on balance and orientation
      tests while the youngsters performed better on sports related gross motor
      movements, processing of speech sounds and had acquired a better relation between
      visual skills and vestibular function. Conclusions were that motor problems do
      not disappear with age and that the same diagnostic instruments and treatment
      methods can be used for both children and adults with sensorimotor difficulties. 

PMID- 25954234
TI  - Dyslexia and configural perception of character sequences.
AB  - Developmental dyslexia is a complex and heterogeneous disorder characterized by
      unexpected difficulty in learning to read. Although it is considered to be
      biologically based, the degree of variation has made the nature and locus of
      dyslexia difficult to ascertain. Hypotheses regarding the cause have ranged from
      low-level perceptual deficits to higher order cognitive deficits, such as
      phonological processing and visual-spatial attention. We applied the capacity
      coefficient, a measure obtained from a mathematical cognitive model of response
      times to measure how efficiently participants processed different classes of
      stimuli. The capacity coefficient was used to test the extent to which
      individuals with dyslexia can be distinguished from normal reading individuals
      based on their ability to take advantage of word, pronounceable non-word,
      consonant sequence or unfamiliar context when categorizing character strings.
      Within subject variability of the capacity coefficient across character string
      types was fairly regular across normal reading adults and consistent with a
      previous study of word perception with the capacity coefficient-words and
      pseudowords were processed at super-capacity and unfamiliar characters strings at
      limited-capacity. Two distinct patterns were observed in individuals with
      dyslexia. One group had a profile similar to the normal reading adults while the
      other group showed very little variation in capacity across string-type. It is
      possible that these individuals used a similar strategy for all four string-types
      and were able to generalize this strategy when processing unfamiliar characters.
      This difference across dyslexia groups may be used to identify sub-types of the
      disorder and suggest significant differences in word level processing among these
      subtypes. Therefore, this approach may be useful in further delineating among
      types of dyslexia, which in turn may lead to better understanding of the
      etiologies of dyslexia. 

PMID- 25954236
TI  - Development of early mathematical skills with a tablet intervention: a randomized
      control trial in Malawi.
AB  - Evaluation of educational interventions is necessary prior to wide-scale rollout.
      Yet very few rigorous studies have been conducted on the effectiveness of tablet
      based interventions, especially in the early years and in developing countries.
      This study reports a randomized control trial to evaluate the effectiveness of a
      tablet intervention for supporting the development of early mathematical skills
      in primary school children in Malawi. A total sample of 318 children, spanning
      Standards 1-3, attending a medium-sized urban primary school, were randomized to
      one of three groups: maths tablet intervention, non-maths tablet control, and
      standard face-to-face practice. Children were pre-tested using tablets at the
      start of the school year on two tests of mathematical knowledge and a range of
      basic skills related to scholastic progression. Class teachers then delivered the
      intervention over an 8-weeks period, for the equivalent of 30-min per day.
      Technical support was provided from the local Voluntary Service Overseas (VSO).
      Children were then post-tested on the same assessments as given at pre-test. A
      final sample of 283 children, from Standards 1-3, present at both pre- and post
      test, was analyzed to investigate the effectiveness of the maths tablet
      intervention. Significant effects of the maths tablet intervention over and above
      standard face-to-face practice or using tablets without the maths software were
      found in Standards 2 and 3. In Standard 3 the greater learning gains shown by the
      maths tablet intervention group compared to both of the control groups on the
      tablet-based assessments transferred to paper and pencil format, illustrating
      generalization of knowledge gained. Thus, tablet technology can effectively
      support early years mathematical skills in developing countries if the software
      is carefully designed to engage the child in the learning process and the content
      is grounded in a solid well-constructed curriculum appropriate for the child's
      developmental stage. 

PMID- 25954235
TI  - The embodied dynamics of perceptual causality: a slippery slope?
AB  - In Michotte's launching displays, while the launcher (object A) seems to move
      autonomously, the target (object B) seems to be displaced passively. However, the
      impression of A actively launching B does not persist beyond a certain distance
      identified as the "radius of action" of A over B. If the target keeps moving
      beyond the radius of action, it loses its passivity and seems to move
      autonomously. Here, we manipulated implied friction by drawing (or not) a surface
      upon which A and B are traveling, and by varying the inclination of this surface
      in screen- and earth-centered reference frames. Among 72 participants (n = 52 in
      Experiment 1; n = 20 in Experiment 2), we show that both physical embodiment of
      the event (looking straight ahead at a screen displaying the event on a vertical
      plane vs. looking downwards at the event displayed on a horizontal plane) and
      contextual information (objects moving along a depicted surface or in isolation)
      affect interpretation of the event and modulate the radius of action of the
      launcher. Using classical mechanics equations, we show that representational
      consistency of friction from radius of action responses emphasizes the embodied
      nature of frictional force in our cognitive architecture. 

PMID- 25954237
TI  - Perceived emotional intelligence as a moderator variable between
      cybervictimization and its emotional impact.
AB  - The negative effects of traditional bullying and, recently, cyberbullying on
      victims are well-documented, and abundant empirical evidence for it exists.
      Cybervictimization affects areas such as academic performance, social integration
      and self-esteem, and causes emotions ranging from anger and sadness to more
      complex problems such as depression. However, not all victims are equally
      affected, and the differences seem to be due to certain situational and personal
      characteristics. The objective of this study is to analyze the relationship
      between perceived emotional intelligence (PEI) and the emotional impact of
      cybervictimization. We hypothesize that EI, which has previously been found to
      play a role in traditional bullying and cyberbullying, may also affect the
      emotional impact of cyberbullying. The participants in our study were 636
      university students from two universities in the south of Spain. Three self
      report questionnaires were used: the "European Cyberbullying Intervention Project
      Questionnaire," the "Cyberbullying Emotional Impact Scale"; and "Trait Meta-Mood
      Scale-24." Structural Equation Models were used to test the relationships between
      the analyzed variables. The results support the idea that PEI, by way of a
      moderator effect, affects the relationship between cybervictimization and
      emotional impact. Taken together, cybervictimization and PEI explain much of the
      variance observed in the emotional impact in general and in the negative
      dimensions of that impact in particular. Attention and Repair were found to be
      inversely related to Annoyance and Dejection, and positively related to
      Invigoration. Clarity has the opposite pattern; a positive relationship with
      Annoyance and Dejection and an inverse relationship with Invigoration. Various
      hypothetical explanations of these patterns are discussed. 

PMID- 25954238
TI  - Erratum: Commentary: "Large-scale psychological differences within China
      explained by rice vs. wheat agriculture".
AB  - [This corrects the article on p. 603 in vol. 344, PMID: 24812395.]. 

PMID- 25954239
TI  - Editorial: Improving visual deficits with perceptual learning.

PMID- 25954241
TI  - Evolved computers with culture. Commentary: From computers to cultivation:
      reconceptualizing evolutionary psychology.

PMID- 25954240
TI  - Sugarcoated isolation: evidence that social avoidance is linked to higher basal
      glucose levels and higher consumption of glucose.
AB  - OBJECTIVE: The human brain adjusts its level of effort in coping with various
      life stressors as a partial function of perceived access to social resources. We
      examined whether people who avoid social ties maintain a higher fasting basal
      level of glucose in their bloodstream and consume more sugar-rich food,
      reflecting strategies to draw more on personal resources when threatened.
      METHODS: In Study 1 (N = 60), we obtained fasting blood glucose and adult
      attachment orientations data. In Study 2 (N = 285), we collected measures of
      fasting blood glucose and adult attachment orientations from older adults of
      mixed gender, using a measure of attachment style different from Study 1. In
      Study 3 (N = 108), we examined the link between trait-like attachment avoidance,
      manipulation of an asocial state, and consumption of sugar-rich food. In Study 4
      (N = 115), we examined whether manipulating the social network will moderate the
      effect of attachment avoidance on consumption of sugar-rich food. RESULTS: In
      Study 1, fasting blood glucose levels corresponded with higher attachment
      avoidance scores after statistically adjusting for time of assessment and
      interpersonal anxiety. For Study 2, fasting blood glucose continued to correspond
      with higher adult attachment avoidance even after statistically adjusting for
      interpersonal anxiety, stress indices, age, gender, social support and body mass.
      In Study 3, people high in attachment avoidance consume more sugar-rich food,
      especially when reminded of asocial tendencies. Study 4 indicated that after
      facing a stressful task in the presence of others, avoidant people gather more
      sugar-rich food than more socially oriented people. CONCLUSION: RESULTS are
      consistent with the suggestion that socially avoidant individuals upwardly adjust
      their basal glucose levels and consume more glucose-rich food with the
      expectation of increased personal effort because of limited access to social
      resources. Further investigation of this link is warranted.

PMID- 25954242
TI  - The attention schema theory: a mechanistic account of subjective awareness.
AB  - We recently proposed the attention schema theory, a novel way to explain the
      brain basis of subjective awareness in a mechanistic and scientifically testable
      manner. The theory begins with attention, the process by which signals compete
      for the brain's limited computing resources. This internal signal competition is
      partly under a bottom-up influence and partly under top-down control. We propose
      that the top-down control of attention is improved when the brain has access to a
      simplified model of attention itself. The brain therefore constructs a schematic
      model of the process of attention, the 'attention schema,' in much the same way
      that it constructs a schematic model of the body, the 'body schema.' The content
      of this internal model leads a brain to conclude that it has a subjective
      experience. One advantage of this theory is that it explains how awareness and
      attention can sometimes become dissociated; the brain's internal models are never
      perfect, and sometimes a model becomes dissociated from the object being modeled.
      A second advantage of this theory is that it explains how we can be aware of both
      internal and external events. The brain can apply attention to many types of
      information including external sensory information and internal information about
      emotions and cognitive states. If awareness is a model of attention, then this
      model should pertain to the same domains of information to which attention
      pertains. A third advantage of this theory is that it provides testable
      predictions. If awareness is the internal model of attention, used to help
      control attention, then without awareness, attention should still be possible but
      should suffer deficits in control. In this article, we review the existing
      literature on the relationship between attention and awareness, and suggest that
      at least some of the predictions of the theory are borne out by the evidence. 

PMID- 25954243
TI  - Acute ischemic stroke treatment, part 1: patient selection "the 50% barrier and
      the capillary index score".
AB  - The current strategy for intra-arterial treatment (IAT) of acute ischemic stroke
      focuses on minimizing time from ictus to revascularization and maximizing
      revascularization. Employing this strategy has yet to lead to improved rates of
      successful outcomes. However, the collateral blood supply likely plays a
      significant role in maintaining viable brain tissue during ischemia. Based on our
      prior work, we believe that only approximately 50% of patients are genetically
      predisposed to have sufficient collaterals for a good outcome following
      treatment, a concept we call the 50% barrier. The Capillary Index Score (CIS) has
      been developed as a tool to identify patients with a sufficient collateral blood
      supply to maintain tissue viability prior to treatment. Patients with a favorable
      CIS (f CIS) may be able to achieve a good outcome with IAT beyond an arbitrary
      time window. The CIS is incorporated into a proposed patient treatment algorithm.
      For patients suffering from a large stroke without aphasia, a non-enhanced head
      CT should be followed by CT angiography (CTA). For patients without signs of
      stroke mimics or visible signs of structural changes due to large irreversible
      ischemia, CTA can help confirm the vascular occlusion and location. The CIS can
      be obtained from a diagnostic cerebral angiogram, with IAT offered to patients
      categorized as f CIS. 

PMID- 25954244
TI  - Editorial: the ischemic penumbra: still the target for stroke therapies?

PMID- 25954245
TI  - A clinical and biochemical analysis in the differential diagnosis of idiopathic
      normal pressure hydrocephalus.
AB  - INTRODUCTION: Idiopathic normal pressure hydrocephalus (iNPH) can be misdiagnosed
      with other neurodegenerative diseases, especially in the early disease stages.
      Considering the opportunity of the shunt surgery, iNPH should be diagnosed with
      accuracy. Here, we evaluate the utility of CSF biomarkers and their relationship
      with clinical features in the diagnosis of iNPH. METHODS: We performed a
      multivariate analysis of the CSF levels of Abeta42, t-tau, and p-tau collected
      from four groups of patients: 14 iNPH, 14 progressive supranuclear palsy (PSP),
      14 Alzheimer's disease (AD), 14 controls (CTL). Diagnostic accuracy of biomarkers
      was determined by the receiver operating characteristic curve analysis.
      Statistical correlation was calculated between each CSF biomarker and single
      clinical items of iNPH. RESULTS: Abeta42 levels in iNPH were lower than controls,
      although not as low as in AD. Likewise, CSF t-tau and p-tau were lower in iNPH
      than in controls. Of interest, t-tau and p-tau were higher in AD than in controls
      and hence both t-tau and p-tau were significantly lower in iNPH than in AD. No
      differences were found between iNPH and PSP. CSF biomarkers levels did not
      correlate to clinical features of iNPH, whereas two significant correlations
      emerged within clinical parameters: cognitive impairment was related to gait
      difficulties, while ventricular enlargement correlated with continence
      disturbances. CONCLUSION: Measurement of CSF biomarker levels may be helpful in
      the differential diagnosis between iNPH and AD but not between iNPH and PSP. Both
      Abeta42 and tau levels appear unrelated to main clinical features of iNPH.

PMID- 25954246
TI  - Quantification of Alterations in Cortical Bone Geometry Using Site Specificity
      Software in Mouse models of Aging and the Responses to Ovariectomy and Altered
      Loading.
AB  - Investigations into the effect of (re)modeling stimuli on cortical bone in
      rodents normally rely on analysis of changes in bone mass and architecture at a
      narrow cross-sectional site. However, it is well established that the effects of
      axial loading produce site-specific changes throughout bones' structure. Non
      mechanical influences (e.g., hormones) can be additional to or oppose locally
      controlled adaptive responses and may have more generalized effects. Tools
      currently available to study site-specific cortical bone adaptation are limited.
      Here, we applied novel site specificity software to measure bone mass and
      architecture at each 1% site along the length of the mouse tibia from standard
      micro-computed tomography (MUCT) images. Resulting measures are directly
      comparable to those obtained through MUCT analysis (R (2) > 0.96). Site
      Specificity analysis was used to compare a number of parameters in tibiae from
      young adult (19-week-old) versus aged (19-month-old) mice; ovariectomized and
      entire mice; limbs subjected to short periods of axial loading or disuse induced
      by sciatic neurectomy. Age was associated with uniformly reduced cortical
      thickness and site-specific decreases in cortical area most apparent in the
      proximal tibia. Mechanical loading site-specifically increased cortical area and
      thickness in the proximal tibia. Disuse uniformly decreased cortical thickness
      and decreased cortical area in the proximal tibia. Ovariectomy uniformly reduced
      cortical area without altering cortical thickness. Differences in polar moment of
      inertia between experimental groups were only observed in the proximal tibia.
      Aging and ovariectomy also altered eccentricity in the distal tibia. In summary,
      site specificity analysis provides a valuable tool for measuring changes in
      cortical bone mass and architecture along the entire length of a bone. Changes in
      the (re)modeling response determined at a single site may not reflect the
      response at different locations within the same bone. 

PMID- 25954247
TI  - Mutant p53 - Heat Shock Response Oncogenic Cooperation: A New Mechanism of Cancer
      Cell Survival.
AB  - The main tumor suppressor function of p53 as a "guardian of the genome" is to
      respond to cellular stress by transcriptional activation of apoptosis, growth
      arrest, or senescence in damaged cells. Not surprisingly, mutations in the p53
      gene are the most frequent genetic alteration in human cancers. Importantly,
      mutant p53 (mutp53) proteins not only lose their wild-type tumor suppressor
      activity but also can actively promote tumor development. Two main mechanisms
      accounting for mutp53 proto-oncogenic activity are inhibition of the wild-type
      p53 in a dominant-negative fashion and gain of additional oncogenic activities
      known as gain-of-function (GOF). Here, we discuss a novel mechanism of mutp53
      GOF, which relies on its oncogenic cooperation with the heat shock machinery.
      This coordinated adaptive mechanism renders cancer cells more resistant to
      proteotoxic stress and provides both, a strong survival advantage to cancer cells
      and a promising means for therapeutic intervention. 

PMID- 25954248
TI  - Romosozumab and blosozumab: alternative drugs of mechanical strain-related
      stimulus toward a cure for osteoporosis.

PMID- 25954249
TI  - Thyroid cell differentiation from murine induced pluripotent stem cells.
AB  - BACKGROUND: Here, we demonstrate the successful differentiation of induced
      pluripotent stem (iPS) cells into functional thyroid cells indicating the
      therapeutic potential of this approach when applied to individuals with thyroid
      deficiency. RESEARCH DESIGN AND METHODS: Using embryonic murine fibroblasts, we
      generated iPS cells with a single lentiviral "stem cell cassette" vector and then
      differentiated these iPS cells into thyroid cells after transfection with PAX8
      and NKX2-1 by Activin A and TSH stimulation. RESULTS: The generated iPS cells
      expressed pluripotent stem cell markers as assessed using both reverse
      transcription quantitative PCRs and immunofluorescence staining with ~0.5%
      reprograming efficiency. Compared to control cells, the expression of thyroid
      specific genes NIS, TSHR, Tg, and TPO were greatly enhanced in PAX8(+)NKX2-1(+)
      iPS cells after differentiation. On stimulation with TSH, these differentiated
      iPS cells were also capable of dose-dependent cAMP generation and radioiodine
      uptake indicative of functional thyroid epithelial cells. Furthermore, the cells
      formed three-dimensional follicles in culture, and "thyroid organoids" formed
      after PAX8(+)NKX2-1(+) iPS cells transplanted into nude mice, and all expressed
      Tg protein as judged immunohistochemically. Taken together, thyroid epithelial
      cells differentiated from iPS cells, which were themselves derived from murine
      fibroblasts, exhibited very similar properties to thyroid cells previously
      developed from traditional murine embryonic stem cells. CONCLUSION: Thyroid cells
      differentiated from iPS cells offer the opportunity to examine the detailed
      transcriptional regulation of thyroid cell differentiation and may provide a
      useful future source for individualized regenerative cell therapy.

PMID- 25954250
TI  - A brief history of bacterial growth physiology.
AB  - Arguably, microbial physiology started when Leeuwenhoek became fascinated by
      observing a Vorticella beating its cilia, my point being that almost any
      observation of microbes has a physiological component. With the advent of modern
      microbiology in the mid-19th century, the field became recognizably distinctive
      with such discoveries as anaerobiosis, fermentation as a biological phenomenon,
      and the nutritional requirements of microbes. Soon came the discoveries of
      Winogradsky and his followers of the chemical changes in the environment that
      result from microbial activities. Later, during the first half of the 20th
      century, microbial physiology became the basis for much of the elucidation of
      central metabolism. Bacterial physiology then became a handmaiden of molecular
      biology and was greatly influenced by the discovery of cellular regulatory
      mechanisms. Microbial growth, which had come of age with the early work of
      Hershey, Monod, and others, was later pursued by studies on a whole cell level by
      what became known as the "Copenhagen School." During this time, the exploration
      of physiological activities became coupled to modern inquiries into the structure
      of the bacterial cell. Recent years have seen the development of a further phase
      in microbial physiology, one seeking a deeper quantitative understanding of
      phenomena on a whole cell level. This pursuit is exemplified by the emergence of
      systems biology, which is made possible by the development of technologies that
      permit the gathering of information in huge amounts. As has been true through
      history, the research into microbial physiology continues to be guided by the
      development of new methods of analysis. Some of these developments may well
      afford the possibility of making stunning breakthroughs. 

PMID- 25954253
TI  - KLIKK proteases of Tannerella forsythia: putative virulence factors with a unique
      domain structure.
AB  - Comparative genomics of virulent Tannerella forsythia ATCC 43037 and a close
      health-associated relative, Tannerella BU063, revealed, in the latter, the
      absence of an entire array of genes encoding putative secretory proteases that
      possess a nearly identical C-terminal domain (CTD) that ends with a -Lys-Leu-Ile
      Lys-Lys motif. This observation suggests that these proteins, referred to as
      KLIKK proteases, may function as virulence factors. Re-sequencing of the loci of
      the KLIKK proteases found only six genes grouped in two clusters. All six genes
      were expressed by T. forsythia in routine culture conditions, although at
      different levels. More importantly, a transcript of each gene was detected in
      gingival crevicular fluid (GCF) from periodontitis sites infected with T.
      forsythia indicating that the proteases are expressed in vivo. In each protein, a
      protease domain was flanked by a unique N-terminal profragment and a C-terminal
      extension ending with the CTD. Partially purified recombinant proteases showed
      variable levels of proteolytic activity in zymography gels and toward protein
      substrates, including collagen, gelatin, elastin, and casein. Taken together,
      these results indicate that the pathogenic strain of T. forsythia secretes active
      proteases capable of degrading an array of host proteins, which likely represents
      an important pathogenic feature of this bacterium. 

PMID- 25954252
TI  - Engineered bacterial hydrophobic oligopeptide repeats in a synthetic yeast prion,
      [REP-PSI (+)].
AB  - The yeast translation termination factor Sup35p, by aggregating as the [PSI (+)]
      prion, enables ribosomes to read-through stop codons, thus expanding the
      diversity of the Saccharomyces cerevisiae proteome. Yeast prions are functional
      amyloids that replicate by templating their conformation on native protein
      molecules, then assembling as large aggregates and fibers. Prions propagate
      epigenetically from mother to daughter cells by fragmentation of such assemblies.
      In the N-terminal prion-forming domain, Sup35p has glutamine/asparagine-rich
      oligopeptide repeats (OPRs), which enable propagation through chaperone-elicited
      shearing. We have engineered chimeras by replacing the polar OPRs in Sup35p by up
      to five repeats of a hydrophobic amyloidogenic sequence from the synthetic
      bacterial prionoid RepA-WH1. The resulting hybrid, [REP-PSI (+)], (i) was
      functional in a stop codon read-through assay in S. cerevisiae; (ii) generates
      weak phenotypic variants upon both its expression or transformation into [psi (
      )] cells; (iii) these variants correlated with high molecular weight aggregates
      resistant to SDS during electrophoresis; and (iv) according to fluorescence
      microscopy, the fusion of the prion domains from the engineered chimeras to the
      reporter protein mCherry generated perivacuolar aggregate foci in yeast cells.
      All these are signatures of bona fide yeast prions. As assessed through
      biophysical approaches, the chimeras assembled as oligomers rather than as the
      fibers characteristic of [PSI (+)]. These results suggest that it is the balance
      between polar and hydrophobic residues in OPRs what determines prion
      conformational dynamics. In addition, our findings illustrate the feasibility of
      enabling new propagation traits in yeast prions by engineering OPRs with
      heterologous amyloidogenic sequence repeats. 

PMID- 25954251
TI  - How much territory can a single E. coli cell control?
AB  - Bacteria have been traditionally classified in terms of size and shape and are
      best known for their very small size. Escherichia coli cells in particular are
      small rods, each 1-2 MU. However, the size varies with the medium, and faster
      growing cells are larger because they must have more ribosomes to make more
      protoplasm per unit time, and ribosomes take up space. Indeed, Maaloe's
      experiments on how E. coli establishes its size began with shifts between rich
      and poor media. Recently much larger bacteria have been described, including
      Epulopiscium fishelsoni at 700 MUm and Thiomargarita namibiensis at 750 MUm.
      These are not only much longer than E. coli cells but also much wider,
      necessitating considerable intracellular organization. Epulopiscium cells for
      instance, at 80 MUm wide, enclose a large enough volume of cytoplasm to present
      it with major transport problems. This review surveys E. coli cells much longer
      than those which grow in nature and in usual lab cultures. These include cells
      mutated in a single gene (metK) which are 2-4 * longer than their non-mutated
      parent. This metK mutant stops dividing when slowly starved of S
      adenosylmethionine but continues to elongate to 50 MUm and more. FtsZ mutants
      have been routinely isolated as long cells which form during growth at 42 degrees
      C. The SOS response is a well-characterized regulatory network that is activated
      in response to DNA damage and also results in cell elongation. Our champion
      elongated E. coli is a metK strain with a further, as yet unidentified mutation,
      which reaches 750 MUm with no internal divisions and no increase in width. 

PMID- 25954254
TI  - Previously unknown evolutionary groups dominate the ssDNA gokushoviruses in oxic
      and anoxic waters of a coastal marine environment.
AB  - Metagenomic studies have revealed that ssDNA phages from the family Microviridae
      subfamily Gokushovirinae are widespread in aquatic ecosystems. It is hypothesized
      that gokushoviruses occupy specialized niches, resulting in differences among
      genotypes traversing water column gradients. Here, we use degenerate primers that
      amplify a fragment of the gene encoding the major capsid protein to examine the
      diversity of gokushoviruses in Saanich Inlet (SI), a seasonally anoxic fjord on
      the coast of Vancouver Island, BC, Canada. Amplicon sequencing of samples from
      the mixed oxic surface (10 m) and deeper anoxic (200 m) layers indicated a
      diverse assemblage of gokushoviruses, with greater richness at 10 m than 200 m. A
      comparison of amplicon sequences with sequences selected on the basis of RFLP
      patterns from eight surface samples collected over a 1-year period revealed that
      gokushovirus diversity was higher in spring and summer during stratification and
      lower in fall and winter after deep-water renewal, consistent with seasonal
      variability within gokushovirus populations. Our results provide persuasive
      evidence that, while specific gokushovirus genotypes may have a narrow host
      range, hosts for gokushoviruses in SI consist of a wide range of bacterial taxa.
      Indeed, phylogenetic analysis of clustered amplicons revealed at least five new
      phylogenetic groups of previously unknown sequences, with the most abundant group
      associated with viruses infecting SUP05, a ubiquitous and abundant member of
      marine oxygen minimum zones. Relatives of SUP05 dominate the anoxic SI waters
      where they drive coupled carbon, nitrogen, and sulfur transformations along the
      redoxline; thus, gokushoviruses are likely important mortality agents of these
      bacteria with concomittant influences on biogeochemical cycling in marine oxygen
      minimum zones. 

PMID- 25954255
TI  - Adenoviral L4 33K forms ring-like oligomers and stimulates ATPase activity of
      IVa2: implications in viral genome packaging.
AB  - The mechanism of genome packaging in adenoviruses (AdVs) is presumed to be
      similar to that of dsDNA viruses including herpesviruses and dsDNA phages. First,
      the empty capsids are assembled after which the viral genome is pushed through a
      unique vertex by a motor which consists of three minimal components: an ATPase, a
      small terminase and a portal. Various components of this motor exist as ring-like
      structures forming a central channel through which the DNA travels during
      packaging. In AdV, the IVa2 protein is believed to function as a packaging
      ATPase, however, the equivalents of the small terminase and the portal have not
      been identified in AdVs. IVa2 interacts with another viral protein late region 4
      (L4) 33K which is important for genome packaging. Both IVa2 and 33K are expressed
      at high levels during the late stage of virus infection. The oligomeric state of
      IVa2 and 33K was analyzed in virus-infected cells, IVa2 and 33K transfected
      cells, AdV particles, or as recombinant purified proteins. Electron microscopy of
      the purified proteins showed ring-like oligomers for both proteins which is
      consistent with their putative roles as a part of the packaging motor. We found
      that the ATPase activity of IVa2 is stimulated in the presence of 33K and the AdV
      genome. Our results suggest that the 33K functions analogous to the small
      terminase proteins and so will be part of the packaging motor complex. 

PMID- 25954256
TI  - Metabolic pathways of Pseudomonas aeruginosa involved in competition with
      respiratory bacterial pathogens.
AB  - BACKGROUND: Chronic airway infection by Pseudomonas aeruginosa considerably
      contributes to lung tissue destruction and impairment of pulmonary function in
      cystic-fibrosis (CF) patients. Complex interplays between P. aeruginosa and other
      co-colonizing pathogens including Staphylococcus aureus, Burkholderia sp., and
      Klebsiella pneumoniae may be crucial for pathogenesis and disease progression.
      METHODS: We generated a library of PA14 transposon insertion mutants to identify
      P. aeruginosa genes required for exploitative and direct competitions with S.
      aureus, Burkholderia cenocepacia, and K. pneumoniae. RESULTS: Whereas wild-type
      PA14 inhibited S. aureus growth, two transposon insertions located in pqsC and
      carB, resulted in reduced growth inhibition. PqsC is involved in the synthesis of
      4-hydroxy-2-alkylquinolines (HAQs), a family of molecules having antibacterial
      properties, while carB is a key gene in pyrimidine biosynthesis. The carB mutant
      was also unable to grow in the presence of B. cepacia and K. pneumoniae but not
      Escherichia coli and S. epidermidis. We further identified a transposon insertion
      in purF, encoding a key enzyme of purine metabolism. This mutant displayed a
      severe growth deficiency in the presence of Gram-negative but not of Gram
      positive bacteria. We identified a beneficial interaction in a bioA transposon
      mutant, unable to grow on rich medium. This growth defect could be restored
      either by addition of biotin or by co-culturing the mutant in the presence of K.
      pneumoniae or E. coli. CONCLUSION: Complex interactions take place between the
      various bacterial species colonizing CF-lungs. This work identified both
      detrimental and beneficial interactions occurring between P. aeruginosa and three
      other respiratory pathogens involving several major metabolic pathways.
      Manipulating these pathways could be used to interfere with bacterial
      interactions and influence the colonization by respiratory pathogens.

PMID- 25954257
TI  - Seawater cultivation of freshwater cyanobacterium Synechocystis sp. PCC 6803
      drastically alters amino acid composition and glycogen metabolism.
AB  - Water use assessment is important for bioproduction using cyanobacteria. For eco
      friendly reasons, seawater should preferably be used for cyanobacteria
      cultivation instead of freshwater. In this study, we demonstrated that the
      freshwater unicellular cyanobacterium Synechocystis sp. PCC 6803 could be grown
      in a medium based on seawater. The Synechocystis wild-type strain grew well in an
      artificial seawater (ASW) medium supplemented with nitrogen and phosphorus
      sources. The addition of HEPES buffer improved cell growth overall, although the
      growth in ASW medium was inferior to that in the synthetic BG-11 medium. The
      levels of proteins involved in sugar metabolism changed depending on the culture
      conditions. The biosynthesis of several amino acids including aspartate,
      glutamine, glycine, proline, ornithine, and lysine, was highly up-regulated by
      cultivation in ASW. Two types of natural seawater (NSW) were also made available
      for the cultivation of Synechocystis cells, with supplementation of both nitrogen
      and phosphorus sources. These results revealed the potential use of seawater for
      the cultivation of freshwater cyanobacteria, which would help to reduce
      freshwater consumption during biorefinery using cyanobacteria. 

PMID- 25954259
TI  - Distribution and diversity of fungi in freshwater sediments on a river catchment
      scale.
AB  - Fungal communities perform essential functions in biogeochemical cycles. However,
      knowledge of fungal community structural changes in river ecosystems is still
      very limited. In the present study, we combined culture-dependent and culture
      independent methods to investigate fungal distribution and diversity in sediment
      on a regional scale in the Songhua River catchment, located in North-East Asia. A
      total of 147 samples over the whole river catchment were analyzed. The results
      showed that compared to the mainstream, the tributaries have a higher fungal
      community organization and culturable fungal concentration, but possess lower
      community dynamics as assessed by denaturing gradient gel electrophoresis (DGGE).
      Furthermore, phylogenetic analysis of DGGE bands showed that Ascomycota and
      Basidiomycota were the predominant community in the Songhua River catchment.
      Redundancy analysis revealed that longitude was the primary factor determining
      the variation of fungal community structure, and fungal biomass was mainly
      related to the total nutrient content. Our findings provide new insights into the
      characteristics of fungal community distribution in a temperate zone river at a
      regional scale, and demonstrate that fungal dispersal is restricted by
      geographical barriers in a whole river catchment. 

PMID- 25954260
TI  - Editorial on: Bacterial pathogens in the non-clinical environment.

PMID- 25954261
TI  - An ace up their sleeve: a transcriptomic approach exposes the AceI efflux protein
      of Acinetobacter baumannii and reveals the drug efflux potential hidden in many
      microbial pathogens.
AB  - The era of antibiotics as a cure-all for bacterial infections appears to be
      coming to an end. The emergence of multidrug resistance in many hospital
      associated pathogens has resulted in "superbugs" that are effectively
      untreatable. Multidrug efflux pumps are well known mediators of bacterial drug
      resistance. Genome sequencing efforts have highlighted an abundance of putative
      efflux pump genes in bacteria. However, it is not clear how many of these pumps
      play a role in antimicrobial resistance. Efflux pump genes that participate in
      drug resistance can be under tight regulatory control and expressed only in
      response to substrates. Consequently, changes in gene expression following
      antimicrobial shock may be used to identify efflux pumps that mediate
      antimicrobial resistance. Using this approach we have characterized several novel
      efflux pumps in bacteria. In one example we recently identified the
      Acinetobacterchlorhexidine efflux protein (AceI) efflux pump in Acinetobacter.
      AceI is a prototype for a novel family of multidrug efflux pumps conserved in
      many proteobacterial lineages. The discovery of this family raises the
      possibility that additional undiscovered intrinsic resistance proteins may be
      encoded in the core genomes of pathogenic bacteria. 

PMID- 25954258
TI  - Genomic and proteomic evidences unravel the UV-resistome of the poly-extremophile
      Acinetobacter sp. Ver3.
AB  - Ultraviolet radiation can damage biomolecules, with detrimental or even lethal
      effects for life. Even though lower wavelengths are filtered by the ozone layer,
      a significant amount of harmful UV-B and UV-A radiation reach Earth's surface,
      particularly in high altitude environments. high-altitude Andean lakes (HAALs)
      are a group of disperse shallow lakes and salterns, located at the Dry Central
      Andes region in South America at altitudes above 3,000 m. As it is considered one
      of the highest UV-exposed environments, HAAL microbes constitute model systems to
      study UV-resistance mechanisms in environmental bacteria at various complexity
      levels. Herein, we present the genome sequence of Acinetobacter sp. Ver3, a
      gammaproteobacterium isolated from Lake Verde (4,400 m), together with further
      experimental evidence supporting the phenomenological observations regarding this
      bacterium ability to cope with increased UV-induced DNA damage. Comparison with
      the genomes of other Acinetobacter strains highlighted a number of unique genes,
      such as a novel cryptochrome. Proteomic profiling of UV-exposed cells identified
      up-regulated proteins such as a specific cytoplasmic catalase, a putative
      regulator, and proteins associated to amino acid and protein synthesis. Down
      regulated proteins were related to several energy-generating pathways such as
      glycolysis, beta-oxidation of fatty acids, and electronic respiratory chain. To
      the best of our knowledge, this is the first report on a genome from a
      polyextremophilic Acinetobacter strain. From the genomic and proteomic data, an
      "UV-resistome" was defined, encompassing the genes that would support the
      outstanding UV-resistance of this strain. 

PMID- 25954262
TI  - The prevalence of Escherichia coli strains with extended spectrum beta-lactamases
      isolated in China.
AB  - The extended-spectrum-lactamases-producing Escherichia coli has rapidly spread
      worldwide. Escherichia coli has been becoming much more resistant to beta-lactam
      antibiotics and other commonly available antimicrobials. We investigated the
      prevalence, resistance, and probable gene type of extended spectrum beta
      lactamases (ESBLs) using minimum inhibitory concentrations (MICs) testing and
      polymerase chain reaction (PCR). We have collected 289 single-patient E. coli
      Isolates based on samples of China from July 2013 to August 2014. This article
      explored that the prevalence of ESBL-producing Isolates showed multi-resistant to
      antimicrobials such as fluoroquinolones, trimethoprim, tetracycline and
      aminoglycosides, and so on. The frequencies of resistance in Isolates were as
      follows: Ciprofloxacin, 74%, gentamicin, 69.5%, levofloxacin, 63%, tobramycin,
      39%, and minocycline, 7.9%. According to our results, 197(68.2%) of the total 289
      Isolates were ESBL-producing strains; further, 172 (87.3%) producers contained
      genes encoding CTX-M enzymes and 142(72.1%) producers contained genes encoding
      TEM enzymes. Most ESBL-producing Escherichia coli has produced more than one type
      of beta-lactamase. Nucleotide sequence analysis has revealed the diversity of
      ESBLs types: CTX-M -15 is in the majority and TEM-135, CTX-M-3, CTX-M-98, CTX-M
      14, CTX-M-142, CTX-M-65, CTX-M-55, CTX-M-27, and CTX-M-123 have been recovered.
      The results confirm that ESBL producers which are common in hospital strains of
      Escherichia coli are resistant to cephalosporins and other antibiotics in China.
      It is important to monitor such strains closely and provide scientific evidence
      of rational application of antibiotics to prevent their spread. 

PMID- 25954263
TI  - Forest floor community metatranscriptomes identify fungal and bacterial responses
      to N deposition in two maple forests.
AB  - Anthropogenic N deposition alters patterns of C and N cycling in temperate
      forests, where forest floor litter decomposition is a key process mediated by a
      diverse community of bacteria and fungi. To track forest floor decomposer
      activity we generated metatranscriptomes that simultaneously surveyed the
      actively expressed bacterial and eukaryote genes in the forest floor, to compare
      the impact of N deposition on the decomposers in two natural maple forests in
      Michigan, USA, where replicate field plots had been amended with N for 16 years.
      Site and N amendment responses were compared using about 74,000 carbohydrate
      active enzyme transcript sequences (CAZymes) in each metatranscriptome. Parallel
      ribosomal RNA (rRNA) surveys of bacterial and fungal biomass and taxonomic
      composition showed no significant differences in either biomass or OTU richness
      between the two sites or in response to N. Site and N amendment were not
      significant variables defining bacterial taxonomic composition, but they were
      significant for fungal community composition, explaining 17 and 14% of the
      variability, respectively. The relative abundance of expressed bacterial and
      fungal CAZymes changed significantly with N amendment in one of the forests, and
      N-response trends were also identified in the second forest. Although the two
      ambient forests were similar in community biomass, taxonomic structure and active
      CAZyme profile, the shifts in active CAZyme profiles in response to N-amendment
      differed between the sites. One site responded with an over-expression of
      bacterial CAZymes, and the other site responded with an over-expression of both
      fungal and different bacterial CAZymes. Both sites showed reduced representation
      of fungal lignocellulose degrading enzymes in N-amendment plots. The
      metatranscriptome approach provided a holistic assessment of eukaryote and
      bacterial gene expression and is applicable to other systems where eukaryotes and
      bacteria interact. 

PMID- 25954264
TI  - Preface to the proceedings of Halophiles 2013.

PMID- 25954265
TI  - Time dynamics of the Bacillus cereus exoproteome are shaped by cellular
      oxidation.
AB  - At low density, Bacillus cereus cells release a large variety of proteins into
      the extracellular medium when cultivated in pH-regulated, glucose-containing
      minimal medium, either in the presence or absence of oxygen. The majority of
      these exoproteins are putative virulence factors, including toxin-related
      proteins. Here, B. cereus exoproteome time courses were monitored by nanoLC-MS/MS
      under low-oxidoreduction potential (ORP) anaerobiosis, high-ORP anaerobiosis, and
      aerobiosis, with a specific focus on oxidative-induced post-translational
      modifications of methionine residues. Principal component analysis (PCA) of the
      exoproteome dynamics indicated that toxin-related proteins were the most
      representative of the exoproteome changes, both in terms of protein abundance and
      their methionine sulfoxide (Met(O)) content. PCA also revealed an interesting
      interconnection between toxin-, metabolism-, and oxidative stress-related
      proteins, suggesting that the abundance level of toxin-related proteins, and
      their Met(O) content in the B. cereus exoproteome, reflected the cellular
      oxidation under both aerobiosis and anaerobiosis. 

PMID- 25954266
TI  - Virulence reduction in bacteriophage resistant bacteria.
AB  - Bacteriophages can influence the abundance, diversity, and evolution of bacterial
      communities. Several bacteriophages have been reported to add virulence factors
      to their host and to increase bacterial virulence. However, lytic bacteriophages
      can also exert a selective pressure allowing the proliferation of strains with
      reduced virulence. This reduction can be explained because bacteriophages use
      structures present on the bacterial surface as receptors, which can be virulence
      factors in different bacterial species. Therefore, strains with modifications in
      these receptors will be resistant to bacteriophage infection and may also exhibit
      reduced virulence. This mini-review summarizes the reports on bacteriophage
      resistant strains with reductions in virulence, and it discusses the potential
      consequences in phage therapy and in the use of bacteriophages to select
      attenuated strains for vaccines. 

PMID- 25954267
TI  - Co-recognition of beta-glucan and chitin and programming of adaptive immunity to
      Aspergillus fumigatus.
AB  - The prevalence of fungal infections has increased concurrently with increases in
      immune suppressive therapies and susceptible individuals. Opportunistic fungal
      pathogens such as Aspergillus fumigatus may exhibit invasive growth and
      dissemination resulting in a high mortality rate. Herein, we discuss how immune
      sensing of germination directs innate immune responses and programs adaptive
      responses that could promote or impair immune protection during periods of
      heightened susceptibility. In infected individuals, Th1 responses are the most
      protective, while Th2 responses lead to poor disease outcomes. In particular, the
      roles of beta-glucan and chitin co-recognition in shaping Th1- and Th2-type
      immunity to fungal infection are explored. We discuss how fungal responses to
      environmental stresses could result in decreased immune protection from
      infection, particularly in response to anti-fungal drugs that target beta-glucan
      synthesis. Furthermore, we consider how experimental modulation of host-pathogen
      interactions might elucidate the mechanisms of protective and detrimental
      immunity and the potential of current and future studies to promote the
      development of improved treatments for patients that respond poorly to existing
      therapies. 

PMID- 25954270
TI  - Of mice, macaques and men: scaling of virus dynamics and immune responses.

PMID- 25954268
TI  - Tetracycline hypersensitivity of an ezrA mutant links GalE and TseB (YpmB) to
      cell division.
AB  - Cell division in bacteria is initiated by the polymerization of FtsZ into a ring
      like structure at midcell that functions as a scaffold for the other cell
      division proteins. In Bacillus subtilis, the conserved cell division protein EzrA
      is involved in modulation of Z-ring formation and coordination of septal
      peptidoglycan synthesis. Here, we show that an ezrA mutant is hypersensitive to
      tetracycline, even when the tetracycline efflux pump TetA is present. This effect
      is not related to the protein translation inhibiting activity of tetracycline.
      Overexpression of FtsL suppresses this phenotype, which appears to be related to
      the intrinsic low FtsL levels in an ezrA mutant background. A transposon screen
      indicated that the tetracycline effect can also be suppressed by overproduction
      of the cell division protein ZapA. In addition, tetracycline sensitivity could be
      suppressed by transposon insertions in galE and the unknown gene ypmB, which was
      renamed tseB (tetracycline sensitivity suppressor of ezrA). GalE is an epimerase
      using UDP-glucose and UDP-N-acetylglucosamine as substrate. Deletion of this
      protein bypasses the synthetic lethality of zapA ezrA and sepF ezrA double
      mutations, indicating that GalE influences cell division. The transmembrane
      protein TseB contains an extracytoplasmic peptidase domain, and a GFP fusion
      shows that the protein is enriched at cell division sites. A tseB deletion causes
      a shorter cell phenotype, indicating that TseB plays a role in cell division. Why
      a deletion of ezrA renders B. subtilis cells hypersensitive for tetracycline
      remains unclear. We speculate that this phenomenon is related to the tendency of
      tetracycline analogs to accumulate into the lipid bilayer, which may destabilize
      certain membrane proteins. 

PMID- 25954271
TI  - Commentary: "The Role of T3 Surface Molecules in the Activation of Human Cells: A
      Two-Stimulus Requirement for IL-2 Production Reflects Events Occurring at a
      Pretranslational Level".

PMID- 25954269
TI  - Single cell genomics indicates horizontal gene transfer and viral infections in a
      deep subsurface Firmicutes population.
AB  - A major fraction of Earth's prokaryotic biomass dwells in the deep subsurface,
      where cellular abundances per volume of sample are lower, metabolism is slower,
      and generation times are longer than those in surface terrestrial and marine
      environments. How these conditions impact biotic interactions and evolutionary
      processes is largely unknown. Here we employed single cell genomics to analyze
      cell-to-cell genome content variability and signatures of horizontal gene
      transfer (HGT) and viral infections in five cells of Candidatus Desulforudis
      audaxviator, which were collected from a 3 km-deep fracture water in the 2.9 Ga
      old Witwatersrand Basin of South Africa. Between 0 and 32% of genes recovered
      from single cells were not present in the original, metagenomic assembly of
      Desulforudis, which was obtained from a neighboring subsurface fracture. We found
      a transposable prophage, a retron, multiple clustered regularly interspaced short
      palindromic repeats (CRISPRs) and restriction-modification systems, and an
      unusually high frequency of transposases in the analyzed single cell genomes.
      This indicates that recombination, HGT and viral infections are prevalent
      evolutionary events in the studied population of microorganisms inhabiting a
      highly stable deep subsurface environment. 

PMID- 25954272
TI  - Intranasal vaccination with an engineered influenza virus expressing the receptor
      binding subdomain of botulinum neurotoxin provides protective immunity against
      botulism and influenza.
AB  - Influenza virus is a negative segmented RNA virus without DNA intermediate. This
      makes it safer as a vaccine delivery vector than most DNA viruses that have
      potential to integrate their genetic elements into host genomes. In this study,
      we developed a universal influenza viral vector, expressing the receptor binding
      subdomain of botulinum neurotoxin A (BoNT/A). We tested the growth characters of
      the engineered influenza virus in chicken eggs and Madin-Darby canine kidney
      epithelial cells (MDCK), and showed that it can be produced to a titer of 5 *
      10(6) plaque forming unites/ml in chicken eggs and MDCK cells. Subsequently, mice
      intranasally vaccinated with the engineered influenza virus conferred protection
      against challenge with lethal doses of active BoNT/A toxin and influenza virus.
      Our results demonstrated the feasibility to develop a dual purpose nasal vaccine
      against both botulism and influenza. 

PMID- 25954273
TI  - Fully human monoclonal antibody inhibitors of the neonatal fc receptor reduce
      circulating IgG in non-human primates.
AB  - The therapeutic management of antibody-mediated autoimmune disease typically
      involves immunosuppressant and immunomodulatory strategies. However, perturbing
      the fundamental role of the neonatal Fc receptor (FcRn) in salvaging IgG from
      lysosomal degradation provides a novel approach - depleting the body of
      pathogenic immunoglobulin by preventing IgG binding to FcRn and thereby
      increasing the rate of IgG catabolism. Herein, we describe the discovery and
      preclinical evaluation of fully human monoclonal IgG antibody inhibitors of FcRn.
      Using phage display, we identified several potent inhibitors of human-FcRn in
      which binding to FcRn is pH-independent, with over 1000-fold higher affinity for
      human-FcRn than human IgG-Fc at pH 7.4. FcRn antagonism in vivo using a human
      FcRn knock-in transgenic mouse model caused enhanced catabolism of exogenously
      administered human IgG. In non-human primates, we observed reductions in
      endogenous circulating IgG of >60% with no changes in albumin, IgM, or IgA. FcRn
      antagonism did not disrupt the ability of non-human primates to mount IgM/IgG
      primary and secondary immune responses. Interestingly, the therapeutic anti-FcRn
      antibodies had a short serum half-life but caused a prolonged reduction in IgG
      levels. This may be explained by the high affinity of the antibodies to FcRn at
      both acidic and neutral pH. These results provide important preclinical proof of
      concept data in support of FcRn antagonism as a novel approach to the treatment
      of antibody-mediated autoimmune diseases. 

PMID- 25954274
TI  - The uses and misuses of multiplex autoantibody assays in systemic autoimmune
      rheumatic diseases.

PMID- 25954277
TI  - Autoantibodies in systemic vasculitis.

PMID- 25954276
TI  - SOCS1 Mimetics and Antagonists: A Complementary Approach to Positive and Negative
      Regulation of Immune Function.
AB  - Suppressors of cytokine signaling (SOCS) are inducible intracellular proteins
      that play essential regulatory roles in both immune and non-immune function. Of
      the eight known members, SOCS1 and SOCS3 in conjunction with regulatory T cells
      play key roles in regulation of the immune system. Molecular tools such as gene
      transfections and siRNA have played a major role in our functional understanding
      of the SOCS proteins where a key functional domain of 12-amino acid residues
      called the kinase inhibitory region (KIR) has been identified on SOCS1 and SOCS3.
      KIR plays a key role in inhibition of the JAK2 tyrosine kinase, which in turn
      plays a key role in cytokine signaling. A peptide corresponding to KIR (SOCS1
      KIR) bound to the activation loop of JAK2 and inhibited tyrosine phosphorylation
      of STAT1alpha transcription factor by JAK2. Cell internalized SOCS1-KIR is a
      potent therapeutic in the experimental allergic encephalomyelitis (EAE) mouse
      model of multiple sclerosis and showed promise in a psoriasis model and a model
      of diabetes-associated cardiovascular disease. By contrast, a peptide, pJAK2(1001
      1013), that corresponds to the activation loop of JAK2 is a SOCS1 antagonist. The
      antagonist enhanced innate and adaptive immune response against a broad range of
      viruses including herpes simplex virus, vaccinia virus, and an EMC picornavirus.
      SOCS mimetics and antagonists are thus potential therapeutics for negative and
      positive regulation of the immune system. 

PMID- 25954275
TI  - The Role of CD44 in Disease Pathophysiology and Targeted Treatment.
AB  - The cell-surface glycoprotein CD44 is involved in a multitude of important
      physiological functions including cell proliferation, adhesion, migration,
      hematopoiesis, and lymphocyte activation. The diverse physiological activity of
      CD44 is manifested in the pathology of a number of diseases including cancer,
      arthritis, bacterial and viral infections, interstitial lung disease, vascular
      disease, and wound healing. This diversity in biological activity is conferred by
      both a variety of distinct CD44 isoforms generated through complex alternative
      splicing, posttranslational modifications (e.g., N- and O-glycosylation),
      interactions with a number of different ligands, and the abundance and spatial
      distribution of CD44 on the cell surface. The extracellular matrix
      glycosaminoglycan hyaluronic acid (HA) is the principle ligand of CD44. This
      review focuses both CD44-hyaluronan dependent and independent CD44 signaling and
      the role of CD44-HA interaction in various pathophysiologies. The review also
      discusses recent advances in novel treatment strategies that exploit the CD44-HA
      interaction either for direct targeting or for drug delivery. 

PMID- 25954278
TI  - S. mansoni Trapping in Lungs Contributes to Resistance to Reinfection.
AB  - Worm transplantation studies show that physiological and reproductive status of
      the worm is influenced by the microenvironment of the host and critical for
      vaccine design. Worm migration studies in rats with (75)Se-methionine labeled
      cercariae demonstrated that resistance to reinfection (R/R) requires a host
      immune response resulting in worm death. In permissive hosts, inflammation due to
      anti eggs immunity leads to host death, whereas in non-permissive hosts this is
      not the case due to reduced egg burdens. Eggs-induced pathology and inflammatory
      debris resulting from immune attack on worms are important for vaccine design.
      Protective immune responses are perhaps induced when naive hosts are vaccinated
      with either schistosome-derived molecules or attenuated cercariae as suggested by
      the induction of protective anti-parasite antibodies and monoclonals. However,
      these immunological strategies rarely produce 85-90% R/R as is achievable by
      portal-caval shunting. Alternatively, induction of anti-schistosoma immunity may
      induce portacaval shunting, seems highly unlikely although not yet tested.
      Differential screening with sera from twice-infected rats, protective (F2x) from
      Fisher vs. non-protective (W2x) from Wistar-Furth rats, was used to identify
      candidate vaccine antigens. 

PMID- 25954279
TI  - Editorial: secretion of cytokines and chemokines by innate immune cells.

PMID- 25954280
TI  - Loss of the Arabidopsis thaliana P4-ATPases ALA6 and ALA7 impairs pollen fitness
      and alters the pollen tube plasma membrane.
AB  - Members of the P4 subfamily of P-type ATPases are thought to create and maintain
      lipid asymmetry in biological membranes by flipping specific lipids between
      membrane leaflets. In Arabidopsis, 7 of the 12 Aminophospholipid ATPase (ALA)
      family members are expressed in pollen. Here we show that double knockout of ALA6
      and ALA7 (ala6/7) results in siliques with a ~2-fold reduction in seed set with a
      high frequency of empty seed positions near the bottom. Seed set was reduced to
      near zero when plants were grown under a hot/cold temperature stress. Reciprocal
      crosses indicate that the ala6/7 reproductive deficiencies are due to a defect
      related to pollen transmission. In-vitro growth assays provide evidence that
      ala6/7 pollen tubes are short and slow, with ~2-fold reductions in both maximal
      growth rate and overall length relative to wild-type. Outcrosses show that when
      ala6/7 pollen are in competition with wild-type pollen, they have a near 0%
      success rate in fertilizing ovules near the bottom of the pistil, consistent with
      ala6/7 pollen having short and slow growth defects. The ala6/7 phenotypes were
      rescued by the expression of either an ALA6-YFP or GFP-ALA6 fusion protein, which
      showed localization to both the plasma membrane and highly-mobile endomembrane
      structures. A mass spectrometry analysis of mature pollen grains revealed
      significant differences between ala6/7 and wild-type, both in the relative
      abundance of lipid classes and in the average number of double bonds present in
      acyl side chains. A change in the properties of the ala6/7 plasma membrane was
      also indicated by a ~10-fold reduction of labeling by lipophilic FM-dyes relative
      to wild-type. Together, these results indicate that ALA6 and ALA7 provide
      redundant activities that function to directly or indirectly change the
      distribution and abundance of lipids in pollen, and support a model in which ALA6
      and ALA7 are critical for pollen fitness under normal and temperature-stress
      conditions. 

PMID- 25954281
TI  - Synthesis of borate cross-linked rhamnogalacturonan II.
AB  - In the present review, we describe current knowledge about synthesis of borate
      crosslinked rhamnogalacturonan II (RG-II) and it physiological roles. RG-II is a
      portion of pectic polysaccharide with high complexity, present in primary cell
      wall. It is composed of homogalacturonan backbone and four distinct side chains
      (A-D). Borate forms ester bonds with the apiosyl residues of side chain A of two
      RG-II monomers to generate borate dimerized RG-II, contributing for the formation
      of networks of pectic polysaccharides. In plant cell walls, more than 90% of RG
      II are dimerized by borate under boron (B) sufficient conditions. Borate
      crosslinking of RG-II in primary cell walls, to our knowledge, is the only
      experimentally proven molecular function of B, an essential trace-element.
      Although abundance of RG-II and B is quite small in cell wall polysaccharides,
      increasing evidence supports that RG-II and its borate crosslinking are critical
      for plant growth and development. Significant advancement was made recently on
      the location and the mechanisms of RG-II synthesis and borate cross-linking.
      Molecular genetic studies have successfully identified key enzymes for RG-II
      synthesis and regulators including B transporters required for efficient
      formation of RG-II crosslinking and consequent normal plant growth. The present
      article focuses recent advances on (i) RG-II polysaccharide synthesis, (ii)
      occurrence of borate crosslinking and (iii) B transport for borate supply to RG
      II. Molecular mechanisms underlying formation of borate RG-II crosslinking and
      the physiological impacts are discussed. 

PMID- 25954282
TI  - Comprehensive analysis of transcriptome response to salinity stress in the
      halophytic turf grass Sporobolus virginicus.
AB  - The turf grass Sporobolus virginicus is halophyte and has high salinity
      tolerance. To investigate the molecular basis of its remarkable tolerance, we
      performed Illumina high-throughput RNA sequencing on roots and shoots of a S.
      virginicus genotype under normal and saline conditions. The 130 million short
      reads were assembled into 444,242 unigenes. A comparative analysis of the
      transcriptome with rice and Arabidopsis transcriptome revealed six turf grass
      specific unigenes encoding transcription factors. Interestingly, all of them
      showed root specific expression and five of them encode bZIP type transcription
      factors. Another remarkable transcriptional feature of S. virginicus was
      activation of specific pathways under salinity stress. Pathway enrichment
      analysis suggested transcriptional activation of amino acid, pyruvate, and
      phospholipid metabolism. Up-regulation of several unigenes, previously shown to
      respond to salt stress in other halophytes was also observed. Gene Ontology
      enrichment analysis revealed that unigenes assigned as proteins in response to
      water stress, such as dehydrin and aquaporin, and transporters such as cation,
      amino acid, and citrate transporters, and H(+)-ATPase, were up-regulated in both
      shoots and roots under salinity. A correspondence analysis of the enriched
      pathways in turf grass cells, but not in rice cells, revealed two groups of
      unigenes similarly up-regulated in the turf grass in response to salt stress; one
      of the groups, showing excessive up-regulation under salinity, included unigenes
      homologos to salinity responsive genes in other halophytes. Thus, the present
      study identified candidate genes involved in salt tolerance of S. virginicus.
      This genetic resource should be valuable for understanding the mechanisms
      underlying high salt tolerance in S. virginicus. This information can also
      provide insight into salt tolerance in other halophytes. 

PMID- 25954283
TI  - Knockin' on pollen's door: live cell imaging of early polarization events in
      germinating Arabidopsis pollen.
AB  - Pollen tubes are an excellent system for studying the cellular dynamics and
      complex signaling pathways that coordinate polarized tip growth. Although several
      signaling mechanisms acting in the tip-growing pollen tube have been described,
      our knowledge on the subcellular and molecular events during pollen germination
      and growth site selection at the pollen plasma membrane is rather scarce. To
      simultaneously track germinating pollen from up to 12 genetically different
      plants we developed an inexpensive and easy mounting technique, suitable for
      every standard microscope setup. We performed high magnification live-cell
      imaging during Arabidopsis pollen activation, germination, and the establishment
      of pollen tube tip growth by using fluorescent marker lines labeling either the
      pollen cytoplasm, vesicles, the actin cytoskeleton or the sperm cell nuclei and
      membranes. Our studies revealed distinctive vesicle and F-actin polarization
      during pollen activation and characteristic growth kinetics during pollen
      germination and pollen tube formation. Initially, the germinating Arabidopsis
      pollen tube grows slowly and forms a uniform roundish bulge, followed by a
      transition phase with vesicles heavily accumulating at the growth site before
      switching to rapid tip growth. Furthermore, we found the two sperm cells to be
      transported into the pollen tube after the phase of rapid tip growth has been
      initiated. The method presented here is suitable to quantitatively study
      subcellular events during Arabidopsis pollen germination and growth, and for the
      detailed analysis of pollen mutants with respect to pollen polarization, bulging,
      or growth site selection at the pollen plasma membrane. 

PMID- 25954284
TI  - The future of starch bioengineering: GM microorganisms or GM plants?
AB  - Plant starches regularly require extensive modification to permit subsequent
      applications. Such processing is usually done by the use of chemical and/or
      physical treatments. The use of recombinant enzymes produced by large-scale
      fermentation of GM microorganisms is increasingly used in starch processing and
      modification, sometimes as an alternative to chemical or physical treatments.
      However, as a means to impart the modifications as early as possible in the
      starch production chain, similar recombinant enzymes may also be expressed in
      planta in the developing starch storage organ such as in roots, tubers and cereal
      grains to provide a GM crop as an alternative to the use of enzymes from GM
      microorganisms. We here discuss these techniques in relation to important
      structural features and modifications of starches such as: starch
      phosphorylation, starch hydrolysis, chain transfer/branching and novel concepts
      of hybrid starch-based polysaccharides. In planta starch bioengineering is
      generally challenged by yield penalties and inefficient production of the desired
      product. However, in some situations, GM crops for starch bioengineering without
      deleterious effects have been achieved. 

PMID- 25954285
TI  - Using RNA-Seq to assemble a rose transcriptome with more than 13,000 full-length
      expressed genes and to develop the WagRhSNP 68k Axiom SNP array for rose (Rosa
      L.).
AB  - In order to develop a versatile and large SNP array for rose, we set out to mine
      ESTs from diverse sets of rose germplasm. For this RNA-Seq libraries containing
      about 700 million reads were generated from tetraploid cut and garden roses using
      Illumina paired-end sequencing, and from diploid Rosa multiflora using 454
      sequencing. Separate de novo assemblies were performed in order to identify
      single nucleotide polymorphisms (SNPs) within and between rose varieties. SNPs
      among tetraploid roses were selected for constructing a genotyping array that can
      be employed for genetic mapping and marker-trait association discovery in
      breeding programs based on tetraploid germplasm, both from cut roses and from
      garden roses. In total 68,893 SNPs were included on the WagRhSNP Axiom array.
      Next, an orthology-guided assembly was performed for the construction of a non
      redundant rose transcriptome database. A total of 21,740 transcripts had
      significant hits with orthologous genes in the strawberry (Fragaria vesca L.)
      genome. Of these 13,390 appeared to contain the full-length coding regions. This
      newly established transcriptome resource adds considerably to the currently
      available sequence resources for the Rosaceae family in general and the genus
      Rosa in particular. 

PMID- 25954286
TI  - Distributions, ex situ conservation priorities, and genetic resource potential of
      crop wild relatives of sweetpotato [Ipomoea batatas (L.) Lam., I. series
      Batatas].
AB  - Crop wild relatives of sweetpotato [Ipomoea batatas (L.) Lam., I. series Batatas]
      have the potential to contribute to breeding objectives for this important root
      crop. Uncertainty in regard to species boundaries and their phylogenetic
      relationships, the limited availability of germplasm with which to perform
      crosses, and the difficulty of introgression of genes from wild species has
      constrained their utilization. Here, we compile geographic occurrence data on
      relevant sweetpotato wild relatives and produce potential distribution models for
      the species. We then assess the comprehensiveness of ex situ germplasm
      collections, contextualize these results with research and breeding priorities,
      and use ecogeographic information to identify species with the potential to
      contribute desirable agronomic traits. The fourteen species that are considered
      the closest wild relatives of sweetpotato generally occur from the central United
      States to Argentina, with richness concentrated in Mesoamerica and in the extreme
      Southeastern United States. Currently designated species differ among themselves
      and in comparison to the crop in their adaptations to temperature, precipitation,
      and edaphic characteristics and most species also show considerable intraspecific
      variation. With 79% of species identified as high priority for further
      collecting, we find that these crop genetic resources are highly under
      represented in ex situ conservation systems and thus their availability to
      breeders and researchers is inadequate. We prioritize taxa and specific
      geographic locations for further collecting in order to improve the completeness
      of germplasm collections. In concert with enhanced conservation of sweetpotato
      wild relatives, further taxonomic research, characterization and evaluation of
      germplasm, and improving the techniques to overcome barriers to introgression
      with wild species are needed in order to mobilize these genetic resources for
      crop breeding. 

PMID- 25954287
TI  - Differential responses to high- and low-dose ultraviolet-B stress in tobacco
      Bright Yellow-2 cells.
AB  - Ultraviolet (UV)-B irradiation leads to DNA damage, cell cycle arrest, growth
      inhibition, and cell death. To evaluate the UV-B stress-induced changes in plant
      cells, we developed a model system based on tobacco Bright Yellow-2 (BY-2) cells.
      Both low-dose UV-B (low UV-B: 740 J m(-2)) and high-dose UV-B (high UV-B: 2960 J
      m(-2)) inhibited cell proliferation and induced cell death; these effects were
      more pronounced at high UV-B. Flow cytometry showed cell cycle arrest within 1
      day after UV-B irradiation; neither low- nor high-UV-B-irradiated cells entered
      mitosis within 12 h. Cell cycle progression was gradually restored in low-UV-B
      irradiated cells but not in high-UV-B-irradiated cells. UV-A irradiation, which
      activates cyclobutane pyrimidine dimer (CPD) photolyase, reduced inhibition of
      cell proliferation by low but not high UV-B and suppressed high-UV-B-induced cell
      death. UV-B induced CPD formation in a dose-dependent manner. The amounts of CPDs
      decreased gradually within 3 days in low-UV-B-irradiated cells, but remained
      elevated after 3 days in high-UV-B-irradiated cells. Low UV-B slightly increased
      the number of DNA single-strand breaks detected by the comet assay at 1 day after
      irradiation, and then decreased at 2 and 3 days after irradiation. High UV-B
      increased DNA fragmentation detected by the terminal deoxynucleotidyl transferase
      dUTP nick end labeling assay 1 and 3 days after irradiation. Caffeine, an
      inhibitor of ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and
      Rad3-related (ATR) checkpoint kinases, reduced the rate of cell death in high-UV
      B-irradiated cells. Our data suggest that low-UV-B-induced CPDs and/or DNA strand
      breaks inhibit DNA replication and proliferation of BY-2 cells, whereas larger
      contents of high-UV-B-induced CPDs and/or DNA strand-breaks lead to cell death. 

PMID- 25954288
TI  - Sensitive detection and measurement of oligogalacturonides in Arabidopsis.
AB  - Oligogalacturonides (OGs) are pectin fragments derived from the partial
      hydrolysis of the plant cell wall pectin; they are elicitors of various defense
      responses. While their activity is well documented, the detection of OGs produced
      in planta is still a challenging task. A protocol has been developed for the
      extraction and analysis of OGs from small samples of Arabidopsis tissues by using
      fluorescent labeled OGs, which allowed to monitor the efficiency of extraction.
      An efficient recovery was obtained by using a combination of calcium chelating
      agents at acidic pH. Off-line coupling of high performance anion exchange
      chromatography with matrix assisted laser desorption ionization- time of flight
      mass spectrometryor nanoESI-Orbitrap-MS/MS was used for the identification and
      characterization of oligosaccharides. The protocol was successfully applied to
      detect OGs by using low amounts (50 mg) of Arabidopsis leaves and very low
      amounts (30 mg) of senescent leaves. The protocol was also successfully used to
      detect OGs in Arabidopsis cell wall material digested with pectinases. The
      proposed extraction protocol followed by sensitive and high-resolution analysis
      methods allowed detection of OGs released from the cell wall in Arabidopsis
      tissues by using minimal sample material. The protocol may be useful to study OG
      triggered plant immunity and cell wall remodeling during Arabidopsis growth and
      development. 

PMID- 25954289
TI  - Differentiation of water-related traits in terrestrial and epiphytic Cymbidium
      species.
AB  - Epiphytes that grow in the canopies of tropical and subtropical forests
      experience different water regimes when compared with terrestrial plants.
      However, the differences in adaptive strategies between epiphytic and terrestrial
      plants with respect to plant water relations remain poorly understood. To
      understand how water-related traits contrast between epiphytic and terrestrial
      growth forms within the Cymbidium (Orchidaceae), we assessed leaf anatomy,
      hydraulics, and physiology of seven terrestrial and 13 epiphytic species using a
      common garden experiment. Compared with terrestrial species, epiphytic species
      had higher values for leaf mass per unit area (LMA), leaf thickness (LT),
      epidermal thickness, saturated water content (SWC) and the time required to dry
      saturated leaves to 70% relative water content (T70). However, vein density
      (Dvein), stomatal density (SD), and photosynthetic capacity (Amax) did not differ
      significantly between the two forms. T70 was positively correlated with LT, LMA,
      and SWC, and negatively correlated with stomatal index (SI). Amax showed positive
      correlations with SD and SI, but not with Dvein. Vein density was marginally
      correlated with SD, and significantly correlated with SI. Overall, epiphytic
      orchids exhibited substantial ecophysiological differentiations from terrestrial
      species, with the former type showing trait values indicative of greater drought
      tolerance and increased water storage capacity. The ability to retain water in
      the leaves plays a key role in maintaining a water balance in those epiphytes.
      Therefore, the process of transpiration depends less upon the current substrate
      water supply and enables epiphytic Cymbidium species to adapt more easily to
      canopy habitats. 

PMID- 25954290
TI  - Two abscission zones proximal to Lansium domesticum fruit: one more sensitive to
      exogenous ethylene than the other.
AB  - Longkong (Lansium domesticum) fruit grows in bunches and is also sold as bunches.
      Individual fruit can separate from the bunch both before and after commercial
      harvest. The fruit has two separation sites. The first is located between bracts
      on the stem and the fused sepals (separation zone 1: SZ1) and the second between
      the fused sepals and the fruit (separation zone 2: SZ2). True abscission occurred
      at both zones. We investigated whether the two zones were active at different
      stages of development and if they were differentially sensitive to ethylene.
      Abscission occurred in the SZ1 in very young fruit (fruit still at the ovary
      stage), during early fruit development (5 weeks after full bloom; WAFB), and in
      ripe and overripe fruit (15-17 WAFB). Abscission did not spontaneously occur in
      the SZ2, but by the time the fruit was fully ripe, 15 WAFB, and later, a slight
      mechanical force was sufficient to break this zone. In fruit bunches severed from
      the tree at 5, 8, and 13 WAFB, break strength (BS) in SZ1 decreased much more
      after exogenous ethylene treatment than that in SZ2. Ethylene induced abscission
      in the SZ1, but not in SZ2. At 5, 8, and 13 WAFB, treatment with 1
      methylcyclopropane (1-MCP; an inhibitor of ethylene perception) had a small
      effect on BS in the SZ1 and no effect in the SZ2. It is concluded that abscission
      in the SZ1 was much more sensitive to ethylene than that in the SZ2. In intact
      plants SZ1 reacts to endogenous ethylene, e.g., as a result of stress, while SZ2
      apparently allows animals to remove the ripe fruit from the tree with minimal
      force. 

PMID- 25954291
TI  - Editorial: "Agrobacterium biology and its application to transgenic plant
      production".

PMID- 25954292
TI  - Acclimation of mechanical and hydraulic functions in trees: impact of the
      thigmomorphogenetic process.
AB  - The secondary xylem (wood) of trees mediates several functions including water
      transport and storage, mechanical support and storage of photosynthates. The
      optimal structures for each of these functions will most likely differ. The
      complex structure and function of xylem could lead to trade-offs between
      conductive efficiency, resistance to embolism, and mechanical strength needed to
      count for mechanical loading due to gravity and wind. This has been referred to
      as the trade-off triangle, with the different optimal solutions to the
      structure/function problems depending on the environmental constraints as well as
      taxonomic histories. Thus, the optimisation of each function will lead to
      drastically different anatomical structures. Trees are able to acclimate the
      internal structure of their trunk and branches according to the stress they
      experience. These acclimations lead to specific structures that favor the
      efficiency or the safety of one function but can be antagonistic with other
      functions. Currently, there are no means to predict the way a tree will acclimate
      or optimize its internal structure in support of its various functions under
      differing environmental conditions. In this review, we will focus on the
      acclimation of xylem anatomy and its resulting mechanical and hydraulic functions
      to recurrent mechanical strain that usually result from wind-induced
      thigmomorphogenesis with a special focus on the construction cost and the
      possible trade-off between wood functions. 

PMID- 25954293
TI  - Structure, expression profile and phylogenetic inference of chalcone isomerase
      like genes from the narrow-leafed lupin (Lupinus angustifolius L.) genome.
AB  - Lupins, like other legumes, have a unique biosynthesis scheme of 5-deoxy-type
      flavonoids and isoflavonoids. A key enzyme in this pathway is chalcone isomerase
      (CHI), a member of CHI-fold protein family, encompassing subfamilies of CHI1,
      CHI2, CHI-like (CHIL), and fatty acid-binding (FAP) proteins. Here, two Lupinus
      angustifolius (narrow-leafed lupin) CHILs, LangCHIL1 and LangCHIL2, were
      identified and characterized using DNA fingerprinting, cytogenetic and linkage
      mapping, sequencing and expression profiling. Clones carrying CHIL sequences were
      assembled into two contigs. Full gene sequences were obtained from these contigs,
      and mapped in two L. angustifolius linkage groups by gene-specific markers.
      Bacterial artificial chromosome fluorescence in situ hybridization approach
      confirmed the localization of two LangCHIL genes in distinct chromosomes. The
      expression profiles of both LangCHIL isoforms were very similar. The highest
      level of transcription was in the roots of the third week of plant growth;
      thereafter, expression declined. The expression of both LangCHIL genes in leaves
      and stems was similar and low. Comparative mapping to reference legume genome
      sequences revealed strong syntenic links; however, LangCHIL2 contig had a much
      more conserved structure than LangCHIL1. LangCHIL2 is assumed to be an ancestor
      gene, whereas LangCHIL1 probably appeared as a result of duplication. As both
      copies are transcriptionally active, questions arise concerning their
      hypothetical functional divergence. Screening of the narrow-leafed lupin genome
      and transcriptome with CHI-fold protein sequences, followed by Bayesian inference
      of phylogeny and cross-genera synteny survey, identified representatives of all
      but one (CHI1) main subfamilies. They are as follows: two copies of CHI2, FAPa2
      and CHIL, and single copies of FAPb and FAPa1. Duplicated genes are remnants of
      whole genome duplication which is assumed to have occurred after the divergence
      of Lupinus, Arachis, and Glycine. 

PMID- 25954295
TI  - Combined moist airtight storage and feed fermentation of barley by the yeast
      Wickerhamomyces anomalus and a lactic acid bacteria consortium.
AB  - This study combined moist airtight storage of moist grain with pig feed
      fermentation. Starter cultures with the potential to facilitate both technologies
      were added to airtight stored moist crimped cereal grain, and the impact on
      storage microflora and the quality of feed fermentations generated from the grain
      was investigated. Four treatments were compared: three based on moist barley,
      either un-inoculated (M), inoculated with Wickerhamomyces anomalus (W), or
      inoculated with W. anomalus and LAB starter culture, containing Pediococcus
      acidilactici DSM 16243, Pediococcus pentosaceus DSM 12834 and Lactobacillus
      plantarum DSM 12837 (WLAB); and one treatment based on dried barley (D). After 6
      weeks of storage, four feed fermentations FM, FW, FWLAB, and FD, were initiated
      from M, W, WLAB, and D, respectively, by mixing the grain with water to a dry
      matter content of 30%. Each treatment was fermented in batch initially for 7 days
      and then kept in a continuous mode by adding new feed daily with 50% back-slop.
      During the 6 week storage period, the average water activity decreased in M, W
      and WLAB from 0.96 to 0.85, and cereal pH decreased from approximately 6.0 at
      harvest to 4.5. Feed fermentation conferred a further pH decrease to 3.8-4.1. In
      M, W and WLAB, molds and Enterobacteriaceae were mostly below detection limit,
      whereas both organism groups were detected in D. In fermented feed,
      Enterobacteriaceae were below detection limit in almost all conditions. Molds
      were detected in FD, for most of the fermentation time in FM and at some sampling
      points in FW and FWLAB. Starter organisms, especially W. anomalus and L.
      plantarum comprised a considerable proportion of the yeast and LAB populations,
      respectively, in both stored grain and fermented feed. However, autochthonous
      Pichia kudriavzevii and Kazachstania exigua partially dominated the yeast
      populations in stored grain and fermented feed, respectively. 

PMID- 25954294
TI  - Naturally occurring diversity helps to reveal genes of adaptive importance in
      legumes.
AB  - Environmental changes challenge plants and drive adaptation to new conditions,
      suggesting that natural biodiversity may be a source of adaptive alleles acting
      through phenotypic plasticity and/or micro-evolution. Crosses between accessions
      differing for a given trait have been the most common way to disentangle genetic
      and environmental components. Interestingly, such man-made crosses may combine
      alleles that never meet in nature. Another way to discover adaptive alleles,
      inspired by evolution, is to survey large ecotype collections and to use
      association genetics to identify loci of interest. Both of these two genetic
      approaches are based on the use of biodiversity and may eventually help us in
      identifying the genes that plants use to respond to challenges such as short-term
      stresses or those due to global climate change. In legumes, two wild species,
      Medicago truncatula and Lotus japonicus, plus the cultivated soybean (Glycine
      max) have been adopted as models for genomic studies. In this review, we will
      discuss the resources, limitations and future plans for a systematic use of
      biodiversity resources in model legumes to pinpoint genes of adaptive importance
      in legumes, and their application in breeding. 

PMID- 25954296
TI  - Tapetum-specific expression of a cytoplasmic orf507 gene causes semi-male
      sterility in transgenic peppers.
AB  - Though cytoplasmic male sterility (CMS) in peppers is associated with the orf507
      gene, definitive and direct evidence that it directly causes male sterility is
      still lacking. In this study, differences in histochemical localization of anther
      cytochrome c oxidase between the pepper CMS line and maintainer line were
      observed mainly in the tapetal cells and tapetal membrane. Inducible and specific
      expression of the orf507 gene in the pepper maintainer line found that
      transformants were morphologically similar to untransformed and transformed
      control plants, but had shrunken anthers that showed little dehiscence and fewer
      pollen grains with lower germination rate and higher naturally damaged rate.
      These characters were different from those of CMS line which does not produce any
      pollen grains. Meanwhile a pollination test using transformants as the male
      parent set few fruit and there were few seeds in the limited number of fruits. At
      the tetrad stage, ablation of the tapetal cell induced by premature programmed
      cell death (PCD) occurred in the transformants and the microspores were distorted
      and degraded at the mononuclear stage. Stable transmission of induced semi-male
      sterility was confirmed by a test cross. In addition, expression of orf507 in the
      maintainer lines seemed to inhibit expression of atp6-2 to a certain extent, and
      lead to the increase of the activity of cytochrome c oxidase and the ATP
      hydrolysis of the mitochondrial F1Fo-ATP synthase. These results introduce the
      premature PCD caused by orf507 gene in tapetal cells and semi-male sterility, but
      not complete male sterility. 

PMID- 25954298
TI  - Allyl isothiocyanate depletes glutathione and upregulates expression of
      glutathione S-transferases in Arabidopsis thaliana.
AB  - Allyl isothiocyanate (AITC) is a phytochemical associated with plant defense in
      plants from the Brassicaceae family. AITC has long been recognized as a
      countermeasure against external threats, but recent reports suggest that AITC is
      also involved in the onset of defense-related mechanisms such as the regulation
      of stomatal aperture. However, the underlying cellular modes of action in plants
      remain scarcely investigated. Here we report evidence of an AITC-induced
      depletion of glutathione (GSH) and the effect on gene expression of the
      detoxification enzyme family glutathione S-transferases (GSTs) in Arabidopsis
      thaliana. Treatment of A. thaliana wild-type with AITC resulted in a time- and
      dose-dependent depletion of cellular GSH. AITC-exposure of mutant lines vtc1 and
      pad2-1 with elevated and reduced GSH-levels, displayed enhanced and decreased
      AITC-tolerance, respectively. AITC-exposure also led to increased ROS-levels in
      the roots and loss of chlorophyll which are symptoms of oxidative stress.
      Following exposure to AITC, we found that GSH rapidly recovered to the same level
      as in the control plant, suggesting an effective route for replenishment of GSH
      or a rapid detoxification of AITC. Transcriptional analysis of genes encoding
      GSTs showed an upregulation in response to AITC. These findings demonstrate
      cellular effects by AITC involving a reversible depletion of the GSH-pool,
      induced oxidative stress, and elevated expression of GST-encoding genes. 

PMID- 25954297
TI  - Transgenic approaches to altering carbon and nitrogen partitioning in whole
      plants: assessing the potential to improve crop yields and nutritional quality.
AB  - The principal components of plant productivity and nutritional value, from the
      standpoint of modern agriculture, are the acquisition and partitioning of organic
      carbon (C) and nitrogen (N) compounds among the various organs of the plant. The
      flow of essential organic nutrients among the plant organ systems is mediated by
      its complex vascular system, and is driven by a series of transport steps
      including export from sites of primary assimilation, transport into and out of
      the phloem and xylem, and transport into the various import-dependent organs.
      Manipulating C and N partitioning to enhance yield of harvested organs is evident
      in the earliest crop domestication events and continues to be a goal for modern
      plant biology. Research on the biochemistry, molecular and cellular biology, and
      physiology of C and N partitioning has now matured to an extent that strategic
      manipulation of these transport systems through biotechnology are being attempted
      to improve movement from source to sink tissues in general, but also to target
      partitioning to specific organs. These nascent efforts are demonstrating the
      potential of applied biomass targeting but are also identifying interactions
      between essential nutrients that require further basic research. In this review,
      we summarize the key transport steps involved in C and N partitioning, and
      discuss various transgenic approaches for directly manipulating key C and N
      transporters involved. In addition, we propose several experiments that could
      enhance biomass accumulation in targeted organs while simultaneously testing
      current partitioning models. 

PMID- 25954299
TI  - Effects of selenium biofortification on crop nutritional quality.
AB  - Selenium (Se) at very low doses has crucial functions in humans and animals.
      Since plants represent the main dietary source of this element, Se-containing
      crops may be used as a means to deliver Se to consumers (biofortification).
      Several strategies have been exploited to increase plant Se content. Selenium
      assimilation in plants affects both sulfur (S) and nitrogen (N) metabolic
      pathways, which is why recent research has also focused on the effect of Se
      fertilization on the production of S- and N- secondary metabolites with putative
      health benefits. In this review we discuss the function of Se in plant and human
      nutrition and the progress in the genetic engineering of Se metabolism to
      increase the levels and bioavailability of this element in food crops. Particular
      attention is paid to Se biofortification and the synthesis of compounds with
      beneficial effects on health. 

PMID- 25954301
TI  - PopPlanner: visually constructing demographic models for simulation.
AB  - Currently there are a number of coalescent simulation programs that support a
      wide range of features, such as arbitrary demographic models, migration, and sub
      structure. Defining the model is done typically with either text files or command
      line switches. Although this has proven to be a powerful method of defining
      models of high complexity, it is often error prone and difficult to read without
      familiarity both with command lines and the program in question. A intuitive GUI
      based population structure program that can both read and write applicable
      command lines would dramatically simplify the construction, modification, and
      error checking of such models by a wider user base. RESULTS: PopPlanner is a tool
      to both construct and inspect complicated demographic models visually with a GUI
      where the user's primary interaction is through mouse gestures. Because of their
      popularity, we focus on ms and by extension msms, command line coalescent
      simulation programs. Our program can be used to find errors with existing command
      lines, or to build original command lines. Furthermore, the graphical output
      supports a number of editing and output features including export of publication
      quality figures.

PMID- 25954300
TI  - Long noncoding RNAs: a potential novel class of cancer biomarkers.
AB  - Long noncoding RNAs (lncRNAs) are a novel class of RNA molecules defined as
      transcripts longer than 200 nucleotides that lack protein coding potential. They
      constitute a major, but still poorly characterized part of human transcriptome,
      however, evidence is growing that they are important regulatory molecules
      involved in various cellular processes. It is becoming increasingly clear that
      many lncRNAs are deregulated in cancer and some of them can be important drivers
      of malignant transformation. On the one hand, some lncRNAs can have highly
      specific expression in particular types of cancer making them a promising tool
      for diagnosis. The expression of other lncRNAs can correlate with different
      pathophysiological features of tumor growth and with patient survival, thus
      making them convenient biomarkers for prognosis. In this review we outline the
      current state of knowledge about the fast growing field of application of lncRNAs
      as tumor biomarkers. 

PMID- 25954302
TI  - Clusters of incompatible genotypes evolve with limited dispersal.
AB  - Theoretical and empirical studies have shown heterogeneous selection to be the
      primary driver for the evolution of reproductively isolated genotypes in the
      absence of geographic barriers. Here, we ask whether limited dispersal alone can
      lead to the evolution of reproductively isolated genotypes despite the absence of
      any geographic barriers or heterogeneous selection. We use a spatially-explicit,
      individual-based, landscape genetics program to explore the influences of
      dispersal strategies on reproductive isolation. We simulated genetic structure in
      a continuously distributed population and across various dispersal strategies
      (ranging from short- to long-range individual movement), as well as potential
      mate partners in entire population (ranging from 20 to 5000 individuals). We show
      that short-range dispersal strategies lead to the evolution of clusters of
      reproductively isolated genotypes despite the absence of any geographic barriers
      or heterogeneous selection. Clusters of genotypes that are reproductively
      isolated from other clusters can persist when migration distances are restricted
      such that the number of mating partners is below about 350 individuals. We
      discuss how our findings may be applicable to particular speciation scenarios, as
      well as the need to investigate the influences of heterogeneous gene flow and
      spatial selection gradients on the emergence of reproductively isolating
      genotypes. 

PMID- 25954304
TI  - Biochemical investigation of a human pathogenic mutation in the nuclear ATP5E
      gene using yeast as a model.
AB  - F1F0-ATP synthase is a key enzyme of the mitochondrial energetic metabolism
      responsible for the production of most cellular ATP in humans. Mayr et al. (2010)
      recently described a patient with a homozygote (Y12C) mutation in the nuclear
      gene ATP5E encoding the epsilon-subunit of ATP synthase. To better define how it
      affects ATP synthase, we have modeled this mutation in the yeast Saccharomyces
      cerevisiae. A yeast equivalent of this mutation (Y11C) had no significant effect
      on the growth of yeast on non-fermentable carbon sources (glycerol/ethanol or
      lactate), conditions under which the activity of the mitochondrial energy
      transducing system is absolutely essential. In addition, similar to what was
      observed in patient, this mutation in yeast has a minimal effect on the
      ATPase/synthase activities. On the contrary, this mutation which has been shown
      to have a strong impact on the assembly of the ATP synthase complex in humans,
      shows no significant impact on the assembly/stability of this complex in yeast,
      suggesting that biogenesis of this complex differs significantly. 

PMID- 25954305
TI  - Modeling the epigenetic attractors landscape: toward a post-genomic mechanistic
      understanding of development.
AB  - Robust temporal and spatial patterns of cell types emerge in the course of normal
      development in multicellular organisms. The onset of degenerative diseases may
      result from altered cell fate decisions that give rise to pathological
      phenotypes. Complex networks of genetic and non-genetic components underlie such
      normal and altered morphogenetic patterns. Here we focus on the networks of
      regulatory interactions involved in cell-fate decisions. Such networks modeled as
      dynamical non-linear systems attain particular stable configurations on gene
      activity that have been interpreted as cell-fate states. The network structure
      also restricts the most probable transition patterns among such states. The so
      called Epigenetic Landscape (EL), originally proposed by C. H. Waddington, was an
      early attempt to conceptually explain the emergence of developmental choices as
      the result of intrinsic constraints (regulatory interactions) shaped during
      evolution. Thanks to the wealth of molecular genetic and genomic studies, we are
      now able to postulate gene regulatory networks (GRN) grounded on experimental
      data, and to derive EL models for specific cases. This, in turn, has motivated
      several mathematical and computational modeling approaches inspired by the EL
      concept, that may be useful tools to understand and predict cell-fate decisions
      and emerging patterns. In order to distinguish between the classical metaphorical
      EL proposal of Waddington, we refer to the Epigenetic Attractors Landscape (EAL),
      a proposal that is formally framed in the context of GRNs and dynamical systems
      theory. In this review we discuss recent EAL modeling strategies, their
      conceptual basis and their application in studying the emergence of both normal
      and pathological developmental processes. In addition, we discuss how model
      predictions can shed light into rational strategies for cell fate regulation, and
      we point to challenges ahead. 

PMID- 25954303
TI  - DNA repair mechanisms in cancer development and therapy.
AB  - DNA damage has been long recognized as causal factor for cancer development. When
      erroneous DNA repair leads to mutations or chromosomal aberrations affecting
      oncogenes and tumor suppressor genes, cells undergo malignant transformation
      resulting in cancerous growth. Genetic defects can predispose to cancer:
      mutations in distinct DNA repair systems elevate the susceptibility to various
      cancer types. However, DNA damage not only comprises a root cause for cancer
      development but also continues to provide an important avenue for chemo- and
      radiotherapy. Since the beginning of cancer therapy, genotoxic agents that
      trigger DNA damage checkpoints have been applied to halt the growth and trigger
      the apoptotic demise of cancer cells. We provide an overview about the
      involvement of DNA repair systems in cancer prevention and the classes of
      genotoxins that are commonly used for the treatment of cancer. A better
      understanding of the roles and interactions of the highly complex DNA repair
      machineries will lead to important improvements in cancer therapy. 

PMID- 25954307
TI  - Are Histrionic Personality Traits Associated with Irritability during Conscious
      Sedation Endoscopy?
AB  - Aim. We aimed to evaluate whether histrionic personality traits are associated
      with irritability during conscious sedation endoscopy (CSE). Materials and
      Methods. A prospective cross-sectional study was planned. Irritability during CSE
      was classified into five grades: 0, no response; I, minimal movement; II,
      moderate movement; III, severe movement; IV, fighting against procedure. Patients
      in grades III and IV were defined as the irritable group. Participants were
      required to complete questionnaire sheet assessing the extent of histrionic
      personality traits, extraversion-introversion, and current psychological status.
      The present authors also collected basic sociodemographic data including alcohol
      use history. Results. A total of 32 irritable patients and 32 stable patients
      were analyzed. The histrionic personality trait score of the irritable group was
      higher than that of the stable group (9.5 +/- 3.1 versus 6.9 +/- 2.9; P = 0.001),
      as was the anxiety score (52.8 +/- 8.6 versus 46.1 +/- 9.6; P = 0.004). Heavy
      alcohol use was more frequently observed in the irritable group (65.6% versus
      28.1%; P = 0.003). In multivariate analysis, all these three factors were
      independently correlated with irritability during CSE. Conclusion. This study
      revealed that histrionic personality traits, anxiety, and heavy alcohol use can
      affect irritability during CSE. 

PMID- 25954306
TI  - Encoding sequential information in semantic space models: comparing holographic
      reduced representation and random permutation.
AB  - Circular convolution and random permutation have each been proposed as neurally
      plausible binding operators capable of encoding sequential information in
      semantic memory. We perform several controlled comparisons of circular
      convolution and random permutation as means of encoding paired associates as well
      as encoding sequential information. Random permutations outperformed convolution
      with respect to the number of paired associates that can be reliably stored in a
      single memory trace. Performance was equal on semantic tasks when using a small
      corpus, but random permutations were ultimately capable of achieving superior
      performance due to their higher scalability to large corpora. Finally, "noisy"
      permutations in which units are mapped to other units arbitrarily (no one-to-one
      mapping) perform nearly as well as true permutations. These findings increase the
      neurological plausibility of random permutations and highlight their utility in
      vector space models of semantics. 

PMID- 25954308
TI  - Repeat upper gastrointestinal endoscopy in patients with functional dyspepsia:
      yield, findings, and predictors of positive findings.
AB  - Background. No guideline on repeat esophagogastroduodenoscopy (EGD) in functional
      dyspepsia (FD) exists. This study aimed to define yield, findings, and predictors
      of positive findings on repeat EGD in FD. Methods. FD patients who underwent at
      least 2 EGDs during October 2005 to November 2011 were enrolled and reviewed.
      Yield and findings were analyzed and univariate and multivariate analyses were
      performed to identify predictors of positive repeat EGD. Results. The median time
      to repeat EGD was 34 months. Among 146 patients, 115 patients (79%) had negative
      and 31 (21%) had positive repeat EGD, including erosive gastritis (13.0%), peptic
      ulcer (7.5%), reflux esophagitis (1.4%), and Barrett's esophagus (0.7%). Four
      independent predictors of positive repeat EGD were smoking (HR 3.88, 95% CI 1.31
      11.51, P = 0.015), hypertension (HR 2.96, 95% CI 1.38-6.36, P = 0.050), history
      of malignancies (HR 3.65, 95% CI 1.16-11.46, P = 0.027), and antiplatelets or
      NSAIDs used within 4 weeks (HR 4.10, 95% CI 1.13-14.90, P = 0.032), while alarm
      features or failure to treatment did not predict positive repeat EGD. 
      Conclusion. Yield of repeat EGD in FD was substantially low, all findings were
      acid-related disorders, and there was no malignancy. Smoking, hypertension,
      history of malignancies, and antiplatelets/NSAIDs use associated with positive
      repeat EGD. 

PMID- 25954309
TI  - The Involvement of GAS6 Signaling in the Development of Obesity and Associated
      Inflammation.
AB  - Growth arrest-specific 6 (GAS6), a vitamin K-dependent protein, plays a role in
      the survival, proliferation, migration, differentiation, adhesion, and apoptosis
      of cells. GAS6 is highly expressed during growth arrest, followed by a sharp
      decrease during differentiation in adipocytes. The functions of GAS6 signaling
      are limited to TAM (Tyro3, Axl, and Mer) receptors and are dependent on the cell
      type. While many studies have focused on the role of GAS6 in inflammation and
      cancer, only few studies focused on its roles of GAS6 in obesity. Accordingly,
      the participation of GAS6 in the progression of obesity remains controversial. In
      this review, we summarize the results of current studies from clinical and basic
      research to elucidate the possible role of GAS6 signaling in obesity and
      associated disorders. In addition, this summary may offer a direction to develop
      clinical therapeutic strategies for the prevention and treatment of obesity and
      related complications. 

PMID- 25954311
TI  - Ectopic Germinal Centers and IgG4-Producing Plasmacytes Observed in Synovia of
      HLA-B27+ Ankylosing Spondylitis Patients with Advanced Hip Involvement.
AB  - Introduction. Ectopic lymphoid neogenesis and the presence of IgG4-positive
      plasmacytes have been confirmed in chronic inflammatory sclerosing diseases. This
      study aims to investigate hip synovial tissues of ankylosing spondylitis (AS)
      patients for IgG4-positive plasma cells and ectopic lymphoid tissues with
      germinal centers (GCs). Methods. Synovial samples were collected from 7 AS
      patients who received total hip replacement and were evaluated using
      immunohistochemistry for the presence of CD20+ B-cells, CD3+ T-cells, CD21+
      follicular dendritic cells (FDC), and CD38+ plasma cells. Furthermore,
      immunoglobulin G (IgG and IgG4), IgA, IgM, and complement components C3d and C4d
      in synovia were evaluated. Both synovial CD21+ FDCs and IgG4-producing
      plasmacytes were analyzed. Results. All seven patients had severe fibrosis.
      Massive infiltrations of lymphocytes were found in 5 out of 7 patients' synovia.
      Ectopic lymphoid tissues with CD21+ FDC networks and IgG4-positive plasma cells
      were observed coincidentally in two patients' synovia. Conclusion. The
      pathophysiological mechanism of AS patients' hip damage might be related to the
      coincidental presence of ectopic lymphoid tissue with FDCs network and IgG4
      positive plasma cells identified here for the first time in AS patients' inflamed
      synovial tissue. 

PMID- 25954310
TI  - Strain US Elastography for the Characterization of Thyroid Nodules: Advantages
      and Limitation.
AB  - Thyroid nodules, with their high prevalence in the general population, represent
      a diagnostic challenge for clinicians. Ultrasound (US), although absolutely
      reliable in detecting thyroid nodules, is still not accurate enough to
      differentiate them into benign and malignant. A promising novel modality, US
      elastography, has been introduced in order to further increase US accuracy. The
      purpose of this review article is to assess the thyroid application of US strain
      elastography, also known as real-time elastography or quasistatic elastography.
      We provide a presentation of the technique, and of up-to-date literature,
      analyzing the most prominent results reported for thyroid nodules
      differentiation. The practical advantages and limitations of strain elastography
      are extensively discussed herein. 

PMID- 25954312
TI  - Prevention of cerebral embolism progression by emergency surgery of the left
      atrial myxoma.
AB  - A 21-year-old woman developed left hemiparesis during work and was hospitalized.
      Her National Institutes of Health Stroke Scale score was 4. Hyperintense areas in
      the left basal ganglia, corona radiata, and cortex of the temporal lobe were
      found by brain diffusion-weighted magnetic resonance imaging, indicating acute
      cerebral infarction. Echocardiography showed a giant mass of diameter 7 * 4 cm in
      the left atrium. Therefore, she was diagnosed with cerebral embolism due to a
      left atrial myxoma. Currently, thrombolytic therapy may continue to be effective
      because the embolic source may be composed of tumor tissue itself. In case of
      atrial myxoma, we considered that the use of tPA as emergency treatment in all
      patients with infarction by atrial myxoma may be questioned. Thus, cardiac tumor
      extraction was performed the next day after hospitalization without thrombolytic
      therapy. The excised myxoma measured 7 * 6 * 4 cm. The patient recovered and her
      neurological symptoms also improved. Furthermore, her National Institutes of
      Health Stroke Scale score improved to 0. Thirteen days after admission, the
      patient was discharged from our hospital. Cardiac myxoma is often associated with
      a high risk of embolic episodes, which emphasizes the need for prompt surgical
      excision as soon as the diagnosis is confirmed. 

PMID- 25954313
TI  - Genetic damage induced by a food coloring dye (sunset yellow) on meristematic
      cells of Brassica campestris L.
AB  - We have performed the present piece of work to evaluate the effect of synthetic
      food coloring azo dye (sunset yellow) on actively dividing root tip cells of
      Brassica campestris L. Three doses of azo dye were administered for the treatment
      of actively dividing root tip cells, namely, 1%, 3%, and 5%, for 6-hour duration
      along with control. Mitotic analysis clearly revealed the azo dye induced
      endpoint deviation like reduction in the frequency of normal divisions in a dose
      dependent manner. Mitotic divisions in the control sets were found to be
      perfectly normal while dose based reduction in MI was registered in the treated
      sets. Azo dye has induced several chromosomal aberrations (genotoxic effect) at
      various stages of cell cycle such as stickiness of chromosomes, micronuclei
      formation, precocious migration of chromosome, unorientation, forward movement of
      chromosome, laggards, and chromatin bridge. Among all, stickiness of chromosomes
      was present in the highest frequency followed by partial genome elimination as
      micronuclei. The present study suggests that extensive use of synthetic dye
      should be forbidden due to genotoxic and cytotoxic impacts on living cells. Thus,
      there is an urgent need to assess potential hazardous effects of these dyes on
      other test systems like human and nonhuman biota for better scrutiny. 

PMID- 25954314
TI  - Efficacy and safety of yokukansan in treatment-resistant schizophrenia: a
      randomized, multicenter, double-blind, placebo-controlled trial.
AB  - Objectives. We aimed at evaluating both the efficacy and safety of TJ-54
      (Yokukansan) in patients with treatment-resistant schizophrenia. This randomized,
      multicenter, double-blind, placebo-controlled study was conducted. Methods. One
      hundred and twenty antipsychotic-treated inpatients were included. Patients were
      randomized to adjuvant treatment with TJ-54 or placebo. During a 4-week follow
      up, psychopathology was assessed using the Positive and Negative Syndrome Scale
      (PANSS). Results. TJ-54 showed a tendency of being superior to placebo in
      reduction total, positive, and general PANSS scores in treatment-resistant
      schizophrenia, but the difference was not statistically significant in both per
      protocol set (PPS) and intention-to-treat (ITT). However, in PPS analysis,
      compared to the placebo group, the TJ-54 group showed statistically significant
      improvements in the individual PANSS subscale scores for lack of spontaneity and
      flow of conversation (TJ-54: -0.23 +/- 0.08; placebo: -0.03 +/- 0.08, P < 0.018),
      tension (TJ-54: -0.42 +/- 0.09; placebo: -0.18 +/- 0.09, P < 0.045), and poor
      impulse control (TJ-54: -0.39 +/- 0.10; placebo: -0.07 +/- 0.10, P < 0.037).
      Conclusions. The results of the present study indicate that TJ-54 showed a
      tendency of being superior to placebo in reduction PANSS scores in treatment
      resistant schizophrenia, but the difference was not statistically significant.
      However, compared to the placebo group, TJ-54 group showed statistically
      significant improvements in the individual PANSS subscale scores. 

PMID- 25954315
TI  - Vitex agnus-castus L. (Verbenaceae) Improves the Liver Lipid Metabolism and Redox
      State of Ovariectomized Rats.
AB  - Vitex agnus-castus (VAC) is a plant that has recently been used to treat the
      symptoms of menopause, by its actions on the central nervous system. However,
      little is known about its actions on disturbances in lipid metabolism and
      nonalcoholic fat liver disease (NAFLD), frequently associated with menopause.
      Ovariectomized (OVX) rats exhibit increased adiposity and NAFLD 13 weeks after
      ovary removal and were used as animal models of estrogen deficiency. The rats
      were treated with crude extract (CE) and a butanolic fraction of VAC (ButF) and
      displayed the beneficial effects of a reduction in the adiposity index and a
      complete reversion of NAFLD. NAFLD reversion was accompanied by a general
      improvement in the liver redox status. The activities of some antioxidant enzymes
      were restored and the mitochondrial hydrogen peroxide production was
      significantly reduced in animals treated with CE and the ButF. It can be
      concluded that the CE and ButF from Vitex agnus-castus were effective in
      preventing NAFLD and oxidative stress, which are frequent causes of abnormal
      liver functions in the postmenopausal period. 

PMID- 25954316
TI  - Antiulcerogenic Activity and Toxicity of Bauhinia holophylla Hydroalcoholic
      Extract.
AB  - Several species of Bauhinia are used in traditional medicine for the treatment of
      gastrointestinal diseases, diabetes, and inflammation, among other conditions.
      The aim of this study was to investigate the antiulcer effect of a hydroalcoholic
      extract from the leaves of B. holophylla. The chemical profile of the extract was
      determined by HPLC-PAD-ESI-IT-MS. A dose-effect relation was constructed using
      the ethanol-induced gastric ulcer model in male Wistar rats. Histological
      analyses and studies of antioxidant and anti-inflammatory activities were
      performed in stomach samples. The involvement of SH compounds, NO, K(+) ATP
      channels, and alpha 2-adrenergic receptors in the gastroprotective effect was
      evaluated. A toxicity study was performed with a single oral dose of 5000 mg/kg.
      The extract was composed mainly of cyanoglucoside and flavonol-O-glycosides
      derivatives of quercetin and myricetin. SH compounds, NO release, K(+) ATP
      channel activation, and presynaptic alpha 2-adrenergic receptor stimulation each
      proved to be involved in the antiulcer effect. The levels of GSH and activity of
      GR and GPx were increased, and the levels of TNF-alpha, IL-6 and IL-10 were
      modulated. There was an antidiarrheal effect and there were no signs of toxicity.
      B. holophylla presents antiulcer activity mainly by decreasing oxidative stress
      and attenuating the inflammatory response, without inducing side effects. 

PMID- 25954317
TI  - The Effect of Ginger (Zingiber officinalis) and Artichoke (Cynara cardunculus)
      Extract Supplementation on Functional Dyspepsia: A Randomised, Double-Blind, and
      Placebo-Controlled Clinical Trial.
AB  - Objective. Functional dyspepsia (FD) is a frequent clinical finding in western
      world. The aim of this study is to compare the efficacy of a ginger and artichoke
      supplementation versus placebo in the treatment of FD. Methods. A prospective
      multicentre, double blind, randomized, placebo controlled, parallel-group
      comparison of the supplement and placebo over a period of 4 weeks was performed.
      Two capsules/day were supplied (before lunch and dinner) to 126 FD patients
      (supplementation/placebo: 65/61). Results. After 14 days of treatment, only
      supplementation group (SG) showed a significant amelioration (SG: alpha S =
      +1.195 MCA score units (u), P = 0.017; placebo: alpha P = +0.347 u, P = 0.513).
      The intercept (alpha) resulted to be significantly higher in SG than in placebo
      (alpha S - alpha P = +0.848 u, P < 0.001). At the end of the study, the advantage
      of SG versus placebo persists without variation (beta S - beta P = +0.077 u, P =
      0.542). In SG, a significant advantage is observed for nausea (beta S - beta P = 
      0.398 u, P < 0.001), epigastric fullness (beta S - beta P = -0.241, P < 0.001),
      epigastric pain (beta S - beta P = -0.173 u, P = 0.002), and bloating (beta S -
      beta P = -0.167 u, P = 0.017). Conclusions. The association between ginger and
      artichoke leaf extracts appears safe and efficacious in the treatment of FD and
      could represent a promising treatment for this disease. 

PMID- 25954318
TI  - A double-blind placebo-controlled trial of maca root as treatment for
      antidepressant-induced sexual dysfunction in women.
AB  - Objective. We sought to demonstrate that maca root may be an effective treatment
      for antidepressant-induced sexual dysfunction (AISD) in women. Method. We
      conducted a 12-week, double-blind, placebo-controlled trial of maca root (3.0
      g/day) in 45 female outpatients (mean age of 41.5 +/- 12.5 years) with SSRI/SNRI
      induced sexual dysfunction whose depression remitted. Endpoints were improvement
      in sexual functioning as per the Arizona Sexual Experience Scale (ASEX) and the
      Massachusetts General Hospital Sexual Function Questionnaire (MGH-SFQ). Results.
      45 of 57 consented females were randomized, and 42 (30 premenopausal and 12
      postmenopausal women) were eligible for a modified intent-to-treat analysis based
      on having had at least one postmedication visit. Remission rates by the end of
      treatment were higher for the maca than the placebo group, based on attainment of
      an ASEX total score <= 10 (9.5% for maca versus 4.8% for placebo), attaining an
      MGH-SFQ score <= 12 (30.0% for maca versus 20.0% for placebo) and reaching an MGH
      SFQ score <= 8 (9.5% for maca versus 5.0% for placebo). Higher remission rates
      for the maca versus placebo group were associated with postmenopausal status.
      Maca was well tolerated. Conclusion. Maca root may alleviate SSRI-induced sexual
      dysfunction in postmenopausal women. This trial is registered with NCT00568126. 

PMID- 25954319
TI  - Proximal humerus derotational osteotomy for internal rotation instability after
      locked posterior shoulder dislocation: early experience in four patients.
AB  - BACKGROUND: We performed a retrospective and descriptive study to determine the
      feasibility of proximal humerus derotational osteotomy in younger patients with
      significant humeral head depression, who may not be good candidates for shoulder
      arthroplasty. METHODS: Rotational osteotomy was done on four patients with a mean
      age of 40 for locked posterior dislocation associated with a reverse Hill-Sachs
      lesion from 2000-2011. The average age was 40 +/- 11 years old and the average
      follow up was 22 +/- 8 months. Shoulder stability, range of motion, radiographic
      outcome and postoperative complications were assessed. Average follow-up was 22
      months (range, 12-30 months) postoperatively. RESULTS: The average range of
      motion of the shoulders at the final follow-up were as follows (Mean +/- Standard
      deviation): Abduction: 125 +/- 29 degrees , Forward flexion: 135 +/- 17 degrees ,
      Internal rotation: 65 +/- 17 degrees , External rotation: 62 +/- 10 degrees .
      There were no wound or neurological complications and no dislocations. Patients
      were satisfied with their functional status and did not have any further symptoms
      of instability or rotator cuff dysfunction. CONCLUSIONS: Proximal humerus
      derotational osteotomy for acute locked posterior dislocation of the shoulder can
      be a viable option for younger age group, which can facilitate rehabilitation for
      these patients by providing immediate stability.

PMID- 25954320
TI  - A balancing act: heterochromatin protein 1a and the Polycomb group coordinate
      their levels to silence chromatin in Drosophila.
AB  - BACKGROUND: The small non-histone protein Heterochromatin protein 1a (HP1a) plays
      a vital role in packaging chromatin, most notably in forming constitutive
      heterochromatin at the centromeres and telomeres. A second major chromatin
      regulating system is that of the Polycomb/trithorax groups of genes which,
      respectively, maintain the repressed/activated state of euchromatin. Recent
      analyses suggest they affect the expression of a multitude of genes, beyond the
      homeotics whose alteration in expression lead to their initial discovery.
      RESULTS: Our data suggest that early in Drosophila development, HP1a collaborates
      with the Polycomb/trithorax groups of proteins to regulate gene expression and
      that the two chromatin systems do not act separately as convention describes.
      HP1a affects the levels of both the Polycomb complexes and RNA polymerase II at
      promoters, as assayed by chromatin immunoprecipitation analysis. Deposition of
      both the repressive (H3K27me3) and activating (H3K4me3) marks promoted by the
      Polycomb/trithorax group genes at gene promoters is affected. Additionally,
      depending on which parent contributes the null mutation of the HP1a gene, the
      levels of the H3K27me3 and H3K9me3 silencing marks at both promoters and
      heterochromatin are different. Changes in levels of the H3K27me3 and H3K9me3
      repressive marks show a mostly reciprocal nature. The time around the mid
      blastula transition, when the zygotic genome begins to be actively transcribed,
      appears to be a transition/decision point for setting the levels. CONCLUSIONS: We
      find that HP1a, which is normally critical for the formation of constitutive
      heterochromatin, also affects the generation of the epigenetic marks of the
      Polycomb/trithorax groups of proteins, chromatin modifiers which are key to
      maintaining gene expression in euchromatin. At gene promoters, deposition of both
      the repressive H3K27me3 and activating H3K4me3 marks of histone modifications
      shows a dependence on HP1a. Around the mid-blastula transition, when the zygotic
      genome begins to be actively transcribed, a pivotal decision for the level of
      silencing appears to take place. This is also when the embryo organizes its
      genome into heterochromatin and euchromatin. A balance between the HP1a and
      Polycomb group silencing systems appears to be set for the chromatin types that
      each system will primarily regulate.

PMID- 25954321
TI  - Calling genotypes from public RNA-sequencing data enables identification of
      genetic variants that affect gene-expression levels.
AB  - BACKGROUND: RNA-sequencing (RNA-seq) is a powerful technique for the
      identification of genetic variants that affect gene-expression levels, either
      through expression quantitative trait locus (eQTL) mapping or through allele
      specific expression (ASE) analysis. Given increasing numbers of RNA-seq samples
      in the public domain, we here studied to what extent eQTLs and ASE effects can be
      identified when using public RNA-seq data while deriving the genotypes from the
      RNA-sequencing reads themselves. METHODS: We downloaded the raw reads for all
      available human RNA-seq datasets. Using these reads we performed gene expression
      quantification. All samples were jointly normalized and subjected to a strict
      quality control. We also derived genotypes using the RNA-seq reads and used
      imputation to infer non-coding variants. This allowed us to perform eQTL mapping
      and ASE analyses jointly on all samples that passed quality control. Our results
      were validated using samples for which DNA-seq genotypes were available. RESULTS:
      4,978 public human RNA-seq runs, representing many different tissues and cell
      types, passed quality control. Even though these data originated from many
      different laboratories, samples reflecting the same cell type clustered together,
      suggesting that technical biases due to different sequencing protocols are
      limited. In a joint analysis on the 1,262 samples with high quality genotypes, we
      identified cis-eQTLs effects for 8,034 unique genes (at a false discovery rate
      <=0.05). eQTL mapping on individual tissues revealed that a limited number of
      samples already suffice to identify tissue-specific eQTLs for known disease
      associated genetic variants. Additionally, we observed strong ASE effects for 34
      rare pathogenic variants, corroborating previously observed effects on the
      corresponding protein levels. CONCLUSIONS: By deriving and imputing genotypes
      from RNA-seq data, it is possible to identify both eQTLs and ASE effects. Given
      the exponential growth of the number of publicly available RNA-seq samples, we
      expect this approach will become especially relevant for studying the effects of
      tissue-specific and rare pathogenic genetic variants to aid clinical
      interpretation of exome and genome sequencing.

PMID- 25954322
TI  - Genome-wide comparison of Asian and African rice reveals high recent activity of
      DNA transposons.
AB  - BACKGROUND: DNA (Class II) transposons are ubiquitous in plant genomes. However,
      unlike for (Class I) retrotransposons, only little is known about their
      proliferation mechanisms, activity, and impact on genomes. Asian and African rice
      (Oryza sativa and O. glaberrima) diverged approximately 600,000 years ago. Their
      fully sequenced genomes therefore provide an excellent opportunity to study
      polymorphisms introduced from recent transposon activity. RESULTS: We manually
      analyzed 1,821 transposon related polymorphisms among which we identified 487
      loci which clearly resulted from DNA transposon insertions and excisions. In
      total, we estimate about 4,000 (3.5% of all DNA transposons) to be polymorphic
      between the two species, indicating a high level of transposable element (TE)
      activity. The vast majority of the recently active elements are non-autonomous.
      Nevertheless, we identified multiple potentially functional autonomous elements.
      Furthermore, we quantified the impacts of insertions and excisions on the
      adjacent sequences. Transposon insertions were found to be generally precise,
      creating simple target site duplications. In contrast, excisions almost always go
      along with the deletion of flanking sequences and/or the insertion of foreign
      'filler' segments. Some of the excision-triggered deletions ranged from hundreds
      to thousands of bp flanking the excision site. Furthermore, we found in some
      superfamilies unexpectedly low numbers of excisions. This suggests that some
      excisions might cause such large-scale rearrangements so that they cannot be
      detected anymore. CONCLUSIONS: We conclude that the activity of DNA transposons
      (particularly the excision process) is a major evolutionary force driving the
      generation of genetic diversity.

PMID- 25954324
TI  - The Impact of HIT on Cost and Quality in Patient-Centered Medical Home Practices.
AB  - While health IT is thought to play a critical role in supporting new models of
      care delivery, we know little about the extent to which HIT improves cost and
      quality outcomes. We studied a large patient-centered medical home (PCMH) program
      to assess which types of HIT led to improvements in composite performance
      outcomes: PMPM cost, chronic disease management, medication management, and
      preventive care. At baseline, registries were associated with lower PMPM spending
      (-$19.37; p<0.05). Over time, practices that newly adopted EHRs had smaller gains
      in chronic disease management adherence relative to non-adopters (diff-in-diff: 
      1.55%; p<0.05). We failed to find a relationship between other types of HIT -
      ePrescribing and PHRs/Portals - and our composite outcomes. The lack of
      consistent relationship between HIT adoption and improved performance suggest
      that these tools may not yet support the clinical activities and approaches to
      patient engagement that enable PCMHs to deliver higher-quality, lower-cost care. 

PMID- 25954323
TI  - Increased clearance of reactive aldehydes and damaged proteins in hypertension
      induced compensated cardiac hypertrophy: impact of exercise training.
AB  - BACKGROUND: We previously reported that exercise training (ET) facilitates the
      clearance of damaged proteins in heart failure. Here, we characterized the impact
      of ET on cardiac protein quality control during compensated ventricular
      hypertrophy in spontaneously hypertensive rats (SHR). METHODS AND RESULTS: SHR
      were randomly assigned into sedentary and swimming-trained groups. Sedentary SHR
      displayed cardiac hypertrophy with preserved ventricular function compared to
      normotensive rats, characterizing a compensated cardiac hypertrophy. Hypertensive
      rats presented signs of cardiac oxidative stress, depicted by increased lipid
      peroxidation. However, these changes were not followed by accumulation of lipid
      peroxidation-generated reactive aldehydes and damaged proteins. This scenario was
      explained, at least in part, by the increased catalytic activity of both aldehyde
      dehydrogenase 2 (ALDH2) and proteasome. Of interest, ET exacerbated cardiac
      hypertrophy, improved ventricular function, induced resting bradycardia, and
      decreased blood pressure in SHR. These changes were accompanied by reduced
      cardiac oxidative stress and a consequent decrease in ALDH2 and proteasome
      activities, without affecting small chaperones levels and apoptosis in SHR.
      CONCLUSION: Increased cardiac ALDH2 and proteasomal activities counteract the
      deleterious effect of excessive oxidative stress in hypertension-induced
      compensated cardiac hypertrophy in rats. ET has a positive effect in reducing
      cardiac oxidative stress without affecting protein quality control.

PMID- 25954326
TI  - Development of an Alert System to Detect Drug Interactions with Herbal
      Supplements using Medical Record Data.
AB  - While potential medication-to-medication interaction alerting engines exist in
      many clinical applications, few systems exist to automatically alert on potential
      medication to herbal supplement interactions. We have developed a preliminary
      knowledge base and rules alerting engine that detects 259 potential interactions
      between 9 supplements, 62 cardiac medications, and 19 drug classes. The rules
      engine takes into consideration 12 patient risk factors and 30 interaction
      warning signs to help determine which of three different alert levels to
      categorize each potential interaction. A formative evaluation was conducted with
      two clinicians to set initial thresholds for each alert level. Additional work is
      planned add more supplement interactions, risk factors, and warning signs as well
      as to continue to set and adjust the inputs and thresholds for each potential
      interaction. 

PMID- 25954325
TI  - Capture of osteoporosis and fracture information in an electronic medical record
      database from primary care.
AB  - In a large database of EMR records, we explore: 1) completeness in capture of
      bone mineral density (BMD) T-scores required for diagnosis of osteoporosis; 2)
      concordance of BMD exam information with other osteoporosis information; and 3)
      evidence of osteoporosis screening among fracture patients. To explore
      completeness of exam capture, BMD exams in the EMR were related to a provincial
      billing database. To explore concordance of information and screening rates, 7500
      EMR records were reviewed for osteoporosis and fracture details. Results show
      that 98% of exams billed to the province for EMR patients were found in the EMR.
      However, documented osteoporosis was substantiated with BMD results only 55.8% of
      the time. Of 151 charts for fragility fracture patients, 1 in 4 contained no
      evidence of osteoporosis investigation. In summary, while EMR information about
      osteoporosis is of variable quality, EMR records shed light on osteoporosis
      management indicators and completely capture BMD results. 

PMID- 25954327
TI  - Factors Contributing to CPOE Opiate Allergy Alert Overrides.
AB  - CONTEXT: Increasing regulatory incentives to computerize provider order entry
      (CPOE) and connect stores of unvalidated allergy information with the electronic
      health record (EHR) has created a perfect storm to overwhelm clinicians with high
      volumes of low or no value drug allergy alerts. Data sources include the patient
      and family, non-clinical staff, nurses, physicians and medical record sources.
      There has been little written on how to collect hypersensitivity information
      suited for drug allergy alerting. Opiates in particular are a frequently ordered
      class of drugs that have one of the highest rates of allergy alert override and
      are often a component of pre-populated Computerized Provider Order Entry (CPOE)
      order sets. Targeted research is needed to reduce alert volume, increase
      clinician acceptance, and improve patient safety and comfort. DESIGN SETTING AND
      PATIENTS: An FY10 retrospective, quantitative analysis of 30321 unique adults
      with opiate allergies triggering CPOE alerts at a large academic medical center.
      MEASUREMENTS: The prevalence of opiates ordered with opiate allergy alerts
      triggered and overridden is described. The effect of age, race, gender, visit
      type (medical, procedural), provider type (physician, advance practice nurse),
      and reaction/severity (e.g. nausea/mild) on the likelihood of provider override
      of the patient's first opiate alert was analyzed using Generalized Estimating
      Equations (GEE). RESULTS: Analysis of a patient's first opiate allergy alert
      (n=2767) showed that only prescriber role had a significant effect on alert
      override compared with all other variables in the model. Advanced practice nurses
      (APNs) were generally less likely to override the patient's first opiate alert as
      compared to physicians (GEE, beta=-.793, beta=.001). However, override rates
      remained high, with 80% for APN's and 90% for physicians. Over half of all
      discharges had opiates ordered during their stay. Of those, 9.1% of the patients
      had recorded opiate allergies triggering 25461 CPOE opiate allergy alerts. The
      largest sub-group of alerts was triggered by gastrointestinal (GI) "allergies"
      such as nausea and constipation. Removing these types of non-allergic, low
      severity GI reactions from the alert pool reduced the first alert volume by 15%
      and the overall alert volume by 22%. Of note is that a history of codeine allergy
      triggered a significant volume of opiate alerts, yet was rarely ordered.
      CONCLUSION: With an increasingly complex, information dependent healthcare
      culture, clinicians do not have unlimited time and cognitive capacity to
      interpret and effectively act on high volumes of low value alerts. Drug allergy
      alerting was one of the earliest and supposedly simplest forms of CPOE clinical
      decision support (CDS), yet still has unacceptably high override rates. Targeted
      strategies to exclude GI non-allergic type hypersensitivities, mild overdose, or
      adverse effects could yield large reductions in overall drug overrides rates.
      Explicit allergy and severity definitions, staff training, and improved clinical
      decision support at the point of allergy data input are needed to inform how we
      process new and re-process historical allergy data.

PMID- 25954329
TI  - Cognitive design of a digital desk for the emergency room setting.
AB  - Digital desk technology has a still mainly unexplored potential to support the
      everyday work of collaborating clinicians. This paper presents ER Desk - a
      digital desk that was designed to specifically support a team of healthcare
      professionals working in an emergency room setting. The underlying design
      requirements were elicited in a comprehensive distributed cognition study of
      paper-based practices in an emergency room of a middle-sized Swedish hospital. We
      present the user interface and visualization requirements for digital desks for
      small clinical emergency room teams. Moreover, we discuss key design issues more
      generally with a focus on supporting team awareness, cognition, and collaborative
      routines of healthcare personnel working in clinical environments such as
      emergency rooms and intensive care units. 

PMID- 25954328
TI  - Application of Bayesian logistic regression to mining biomedical data.
AB  - Mining high dimensional biomedical data with existing classifiers is challenging
      and the predictions are often inaccurate. We investigated the use of Bayesian
      Logistic Regression (B-LR) for mining such data to predict and classify various
      disease conditions. The analysis was done on twelve biomedical datasets with
      binary class variables and the performance of B-LR was compared to those from
      other popular classifiers on these datasets with 10-fold cross validation using
      the WEKA data mining toolkit. The statistical significance of the results was
      analyzed by paired two tailed t-tests and non-parametric Wilcoxon signed-rank
      tests. We observed overall that B-LR with non-informative Gaussian priors
      performed on par with other classifiers in terms of accuracy, balanced accuracy
      and AUC. These results suggest that it is worthwhile to explore the application
      of B-LR to predictive modeling tasks in bioinformatics using informative
      biological prior probabilities. With informative prior probabilities, we
      conjecture that the performance of B-LR will improve. 

PMID- 25954330
TI  - Learning to identify treatment relations in clinical text.
AB  - In clinical notes, physicians commonly describe reasons why certain treatments
      are given. However, this information is not typically available in a computable
      form. We describe a supervised learning system that is able to predict whether or
      not a treatment relation exists between any two medical concepts mentioned in
      clinical notes. To train our prediction model, we manually annotated 958
      treatment relations in sentences selected from 6,864 discharge summaries. The
      features used to indicate the existence of a treatment relation between two
      medical concepts consisted of lexical and semantic information associated with
      the two concepts as well as information derived from the MEDication Indication
      (MEDI) resource and SemRep. The best F1-measure results of our supervised
      learning system (84.90) were significantly better than the F1-measure results
      achieved by SemRep (72.34). 

PMID- 25954331
TI  - An exploration of the potential reach of smartphones in diabetes.
AB  - Although smartphones bear potential to improve diabetes self-management, the
      reach of smartphones in diabetic populations remains uncertain. Using survey data
      from the Pew Research Center, we compared smartphone use in individuals with and
      without diabetes, and determined factors associated with smartphone use among
      those with diabetes. Of the 2989 adults surveyed, 1360 were smartphone users, and
      332 individuals had diabetes. Compared to individuals without diabetes, adults
      with diabetes were less likely to be smartphone users (relative risk of 0.43, 95%
      CI 0.31 to 0.54) even after adjusting for age, race, ethnicity and socioeconomic
      status (adjusted RR of 0.78, 95%CI 0.57-0.98). Among individuals with diabetes,
      high income, younger age and online health information seeking were associated
      with higher smartphone use. While smartphones can reach subgroups for diabetes
      care and prevention (racial/ethnic minorities, newly diagnosed individuals),
      studies are needed to understand this current difference in smartphone use. 

PMID- 25954332
TI  - Analyzing U.S. prescription lists with RxNorm and the ATC/DDD Index.
AB  - OBJECTIVES: To evaluate the suitability of the ATC/DDD Index (Anatomical
      Therapeutic Chemical (ATC) Classification System/Defined Daily Dose) for
      analyzing prescription lists in the U.S. METHODS: We mapped RxNorm clinical drugs
      to ATC. We used this mapping to classify a large set of prescription drugs with
      ATC and compared the prescribed daily dose to the defined daily dose (DDD) in
      ATC. RESULTS: 64% of the 11,422 clinical drugs could be precisely mapped to ATC.
      97% of the 87,001 RxNorm codes from the prescription dataset could be classified
      with ATC, and 97% of the prescribed daily doses could be assessed. CONCLUSIONS:
      Although the mapping of RxNorm ingredients to ATC appears to be largely
      incomplete, the most frequently prescribed drugs in the prescription dataset we
      analyzed were covered. This study demonstrates the feasibility of using ATC in
      conjunction with RxNorm for analyzing U.S. prescription datasets for drug
      classification and assessment of the prescribed daily doses.

PMID- 25954333
TI  - Data Quality and Interoperability Challenges for eHealth Exchange Participants:
      Observations from the Department of Veterans Affairs' Virtual Lifetime Electronic
      Record Health Pilot Phase.
AB  - Authors studied the United States (U.S.) Department of Veterans Affairs' (VA)
      Virtual Lifetime Electronic Record (VLER) Health pilot phase relative to two
      attributes of data quality - the adoption of eHealth Exchange data standards, and
      clinical content exchanged. The VLER Health pilot was an early effort in testing
      implementation of eHealth Exchange standards and technology. Testing included
      evaluation of exchange data from the VLER Health pilot sites partners: VA, U.S.
      Department of Defense (DoD), and private sector health care organizations.
      Domains assessed data quality and interoperability as it relates to: 1)
      conformance with data standards related to the underlying structure of C32
      Summary Documents (C32) produced by eHealth Exchange partners; and 2) the types
      of C32 clinical content exchanged. This analysis identified several standards non
      conformance issues in sample C32 files and informed further discourse on the
      methods needed to effectively monitor Health Information Exchange (HIE) data
      content and standards conformance. 

PMID- 25954334
TI  - Health information technology: use it well, or don't! Findings from the use of a
      decision support system for breast cancer management.
AB  - The potential of health information technology is hampered by new types of errors
      which impact is not totally assessed. OncoDoc2 is a decision support system
      designed to support treatment decisions of multidisciplinary meetings (MDMs) for
      breast cancer patients. We evaluated how the way the system was used had an
      impact on MDM decision compliance with clinical practice guidelines. We
      distinguished "correct navigations" (N+), "incorrect navigations" (N-), and
      "missing navigations" (N0), according to the quality of data entry when using
      OncoDoc2. We collected 557 MDM decisions from three hospitals of Paris area
      (France) where OncoDoc2 was routinely used. We observed 33.9% N+, 36.8% N-, and
      29.3% N0. The compliance rate was significantly different according to the
      quality of navigations, 94.2%, 80.0%, and 90.2% for N+, N-, and N0 respectively.
      Surprinsingly, it was better not to use the system (N0) than to use it improperly
      (N-). 

PMID- 25954335
TI  - Impacts of EHR Certification and Meaningful Use Implementation on an Integrated
      Delivery Network.
AB  - Three years ago Intermountain Healthcare made the decision to participate in the
      Medicare and Medicaid Electronic Heath Record (EHR) Incentive Program which
      required that hospitals and providers use a certified EHR in a meaningful way. At
      that time, the barriers to enhance our home grown system, and change clinician
      workflows were numerous and large. This paper describes the time and effort
      required to enhance our legacy systems in order to pass certification, including
      filling 47 gaps in (EHR) functionality. We also describe the processes and
      resources that resulted in successful changes to many clinical workflows required
      by clinicians to meet meaningful use requirements. In 2011 we set meaningful use
      targets of 75% of employed physicians and 75% of our hospitals to meet Stage 1 of
      meaningful use by 2013. By the end of 2013, 87% of 696 employed eligible
      professionals and 100% of 22 Intermountain hospitals had successfully attested
      for Stage 1. This paper describes documented and perceived costs to Intermountain
      including time, effort, resources, postponement of other projects, as well as
      documented and perceived benefits of attainment of meaningful use. 

PMID- 25954336
TI  - Developing an eBook-Integrated High-Fidelity Mobile App Prototype for Promoting
      Child Motor Skills and Taxonomically Assessing Children's Emotional Responses
      Using Face and Sound Topology.
AB  - Developing gross and fine motor skills and expressing complex emotion is critical
      for child development. We introduce "StorySense", an eBook-integrated mobile app
      prototype that can sense face and sound topologies and identify movement and
      expression to promote children's motor skills and emotional developmental.
      Currently, most interactive eBooks on mobile devices only leverage "low-motor"
      interaction (i.e. tapping or swiping). Our app senses a greater breath of motion
      (e.g. clapping, snapping, and face tracking), and dynamically alters the
      storyline according to physical responses in ways that encourage the performance
      of predetermined motor skills ideal for a child's gross and fine motor
      development. In addition, our app can capture changes in facial topology, which
      can later be mapped using the Facial Action Coding System (FACS) for later
      interpretation of emotion. StorySense expands the human computer interaction
      vocabulary for mobile devices. Potential clinical applications include child
      development, physical therapy, and autism. 

PMID- 25954338
TI  - The Challenges of Creating a Gold Standard for De-identification Research.
AB  - We created a Gold Standard corpus comprised over 20,000 records of annotated
      narrative clinical reports for use in the training and evaluation of NLM
      Scrubber, a de-identification software system for medical records. Our experience
      with designing the corpus demonstrated the conceptual complexity of the task. 

PMID- 25954337
TI  - Making audit actionable: an example algorithm for blood pressure management in
      chronic kidney disease.
AB  - Despite widespread use of clinical guidelines, actual care often falls short of
      ideal standards. Electronic health records (EHR) can be analyzed to provide
      information on how to improve care, but this is seldom done in sufficient detail
      to guide specific action. We developed an algorithm to provide practical,
      actionable information for care quality improvement using blood pressure (BP)
      management in chronic kidney disease (CKD) as an exemplar. We used UK clinical
      guidelines and EHR data from 440 patients in Salford (UK) to develop the
      algorithm. We then applied it to 532,409 individual patient records, identifying
      11,097 CKD patients, 3,766 (34%) of which showed room for improvement in their
      care: either through medication optimization or better BP monitoring. Manual
      record reviews to evaluate accuracy indicated a positive-predictive value of 90%.
      Such algorithms could help improve the management of chronic conditions by
      providing the missing link between clinical audit and decision support. 

PMID- 25954339
TI  - Adoption of clinical data exchange in community settings: a comparison of two
      approaches.
AB  - Adoption of electronic clinical data exchange (CDE) across disparate healthcare
      organizations remains low in community settings despite demonstrated benefits. To
      expand CDE in communities, New York State funded sixteen community-based
      organizations to implement point-to-point directed exchange (n=8) and multi-site
      query-based health information exchange (HIE) (n=8). We conducted a cross
      sectional study to compare adoption of directed exchange versus query-based HIE.
      From 2008 to 2011, 66% (n=1,747) of providers targeted for directed exchange and
      21% (n=5,427) of providers targeted for query-based HIE adopted CDE. Funding per
      provider adoptee was almost two times greater for directed exchange (median
      (interquartile range): $25,535 ($17,391-$42,240)) than query-based HIE ($14,649
      ($9,897-$28,078)), although the difference was not statistically significant.
      Because its infrastructure can cover larger populations using similar levels of
      public funding, query-based HIE may scale more broadly than directed exchange. To
      our knowledge, this is among the first studies to compare directed exchange
      versus query-based HIE. 

PMID- 25954340
TI  - Examining the use, contents, and quality of free-text tobacco use documentation
      in the Electronic Health Record.
AB  - Recent initiatives have emphasized the potential role of Electronic Health Record
      (EHR) systems for improving tobacco use assessment and cessation. In support of
      these efforts, the goal of the present study was to examine tobacco use
      documentation in the EHR with an emphasis on free-text. Three coding schemes were
      developed and applied to analyze 525 tobacco use entries, including structured
      fields and a free-text comment field, from the social history module of an EHR
      system to characterize: (1) potential reasons for using free-text, (2) contents
      within the free-text, and (3) data quality issues. Free-text was most commonly
      used due to limitations for describing tobacco use amount (23.2%), frequency
      (26.9%), and start or quit dates (28.2%) as well as secondhand smoke exposure
      (17.9%) using a variety of words and phrases. The collective results provide
      insights for informing system enhancements, user training, natural language
      processing, and standards for tobacco use documentation. 

PMID- 25954341
TI  - Automated Assessment of Medical Students' Clinical Exposures according to AAMC
      Geriatric Competencies.
AB  - Competence is essential for health care professionals. Current methods to assess
      competency, however, do not efficiently capture medical students' experience. In
      this preliminary study, we used machine learning and natural language processing
      (NLP) to identify geriatric competency exposures from students' clinical notes.
      The system applied NLP to generate the concepts and related features from notes.
      We extracted a refined list of concepts associated with corresponding
      competencies. This system was evaluated through 10-fold cross validation for six
      geriatric competency domains: "medication management (MedMgmt)", "cognitive and
      behavioral disorders (CBD)", "falls, balance, gait disorders (Falls)", "self-care
      capacity (SCC)", "palliative care (PC)", "hospital care for elders (HCE)" - each
      an American Association of Medical Colleges competency for medical students. The
      systems could accurately assess MedMgmt, SCC, HCE, and Falls competencies with F
      measures of 0.94, 0.86, 0.85, and 0.84, respectively, but did not attain good
      performance for PC and CBD (0.69 and 0.62 in F-measure, respectively). 

PMID- 25954342
TI  - Exploring the use patterns of a mobile health application for alcohol addiction
      before the initial lapse after detoxification.
AB  - How patients used Addiction-Comprehensive Health Enhancement Support System (A
      CHESS)1, a mobile health intervention, while quitting drinking is worthy
      exploring. This study is to explore A-CHESS use patterns prior to the initial
      lapse reported after discharge from inpatient detoxification programs. 142
      patients with alcohol addiction from two treatment agencies in the U.S. were
      included. A comprehensive set of A-CHESS use measures were developed based on a
      three-level system use framework and three A-CHESS service categories. In latent
      profile analyses, three A-CHESS system use patterns-inactive, passive, and active
      users-were found. Compared to the passive users (with the highest chance of the
      initial lapse), the active users (with the lowest chance of such behavior)
      participated more in online social activities, used more sessions, viewed more
      pages, and used A-CHESS longer. However, the chances of the initial lapse between
      A-CHESS user profiles were not statistically different. Implications of this
      finding were provided. 

PMID- 25954343
TI  - Online deviation detection for medical processes.
AB  - Human errors are a major concern in many medical processes. To help address this
      problem, we are investigating an approach for automatically detecting when
      performers of a medical process deviate from the acceptable ways of performing
      that process as specified by a detailed process model. Such deviations could
      represent errors and, thus, detecting and reporting deviations as they occur
      could help catch errors before harm is done. In this paper, we identify important
      issues related to the feasibility of the proposed approach and empirically
      evaluate the approach for two medical procedures, chemotherapy and blood
      transfusion. For the evaluation, we use the process models to generate sample
      process executions that we then seed with synthetic errors. The process models
      describe the coordination of activities of different process performers in
      normal, as well as in exceptional situations. The evaluation results suggest that
      the proposed approach could be applied in clinical settings to help catch errors
      before harm is done. 

PMID- 25954344
TI  - Adapting a Clinical Data Repository to ICD-10-CM through the use of a Terminology
      Repository.
AB  - Clinical data repositories frequently contain patient diagnoses coded with the
      International Classification of Diseases, Ninth Revision (ICD-9-CM). These
      repositories now need to accommodate data coded with the Tenth Revision (ICD-10
      CM). Database users wish to retrieve relevant data regardless of the system by
      which they are coded. We demonstrate how a terminology repository (the Research
      Entities Dictionary or RED) serves as an ontology relating terms of both ICD
      versions to each other to support seamless version-independent retrieval from the
      Biomedical Translational Research Information System (BTRIS) at the National
      Institutes of Health. We make use of the Center for Medicare and Medicaid
      Services' General Equivalence Mappings (GEMs) to reduce the modeling effort
      required to determine whether ICD-10-CM terms should be added to the RED as new
      concepts or as synonyms of existing concepts. A divide-and-conquer approach is
      used to develop integration heuristics that offer a satisfactory interim solution
      and facilitate additional refinement of the integration as time and resources
      allow. 

PMID- 25954345
TI  - Clinical Workflow Observations to Identify Opportunities for Nurse, Physicians
      and Patients to Share a Patient-centered Plan of Care.
AB  - Patient- and Family-Centered Care (PFCC) is essential for high quality care in
      the critical and acute-specialty care hospital setting. Effective PFCC requires
      clinicians to form an integrated interprofessional team to collaboratively engage
      with the patient/family and contribute to a shared patient-centered plan of care.
      We conducted observations on a critical care and specialty unit to understand the
      plan of care activities and workflow documentation requirements for nurses and
      physicians to inform the development of a shared patient-centered plan of care to
      support patient engagement. We identified siloed plan of care documentation, with
      workflow opportunities to converge the nurses plan of care with the physician
      planned To-do lists and quality and safety checklists. Integration of nurses and
      physicians plan of care activities into a shared plan of care is a feasible and
      valuable step toward interprofessional teams that effectively engage patients in
      plan of care activities. 

PMID- 25954346
TI  - Development and implementation of a real-time 30-day readmission predictive
      model.
AB  - Hospitals are under great pressure to reduce readmissions of patients. Being able
      to reliably predict patients at increased risk for rehospitalization would allow
      for tailored interventions to be offered to them. This requires the creation of a
      functional predictive model specifically designed to support real-time clinical
      operations. A predictive model for readmissions within 30 days of discharge was
      developed using retrospective data from 45,924 MGH admissions between 2/1/2012
      and 1/31/2013 only including factors that would be available by the day after
      admission. It was then validated prospectively in a real-time implementation for
      3,074 MGH admissions between 10/1/2013 and 10/31/2013. The model developed
      retrospectively had an AUC of 0.705 with good calibration. The real-time
      implementation had an AUC of 0.671 although the model was overestimating
      readmission risk. A moderately discriminative real-time 30-day readmission
      predictive model can be developed and implemented in a large academic hospital. 

PMID- 25954347
TI  - A Semantic-based Approach for Exploring Consumer Health Questions Using UMLS.
AB  - NetWellness is a non-profit web service providing high quality health
      information. It has been in operation since 1995 with over 13 million visits per
      year by consumers across the world in recent years. Consumer questions in
      NetWellness have been answered by medical and health professional faculties at
      three Ohio partner universities: Case Western Reserve University, the Ohio State
      University, and University of Cincinnati. However, the resident interface in
      NetWellness is ineffective in searching existing questions that have already been
      carefully answered by experts in an easy-to-understand manner. In our previous
      work, we presented a Conjunctive Exploratory Navigation Interface (CENI) reusing
      NetWellness' 120 pre-defined health topics in assisting question retrieval. This
      paper presents a novel semantic-based search interface called Semantic
      Conjunctive Exploratory Navigation Interface (SCENI), using UMLS concepts as
      topics. 60,000 questions were tagged by UMLS Concept Unique Identifies (CUIs),
      with each question allowing multiple possible tags. Using a slightly modified 5
      point Likert scale for relevance, SCENI reveals improved precision and relevance
      (precision: 93.47%, relevance: 4.31) in comparison to CENI using NetWellness' pre
      defined topics alone (precision: 77.85%, relevance: 3.3) and NetWellness'
      resident search interface (precision: 50.62%, relevance: 1.97), on a set of
      sample queries. 

PMID- 25954348
TI  - Semantic processing to identify adverse drug event information from black box
      warnings.
AB  - Adverse drug events account for two million combined injuries, hospitalizations,
      or deaths each year. Furthermore, there are few comprehensive, up-to-date, and
      free sources of drug information. Clinical decision support systems may
      significantly mitigate the number of adverse drug events. However, these systems
      depend on up-to-date, comprehensive, and codified data to serve as input. The
      DailyMed website, a resource managed by the FDA and NLM, contains all currently
      approved drugs. We used a semantic natural language processing approach that
      successfully extracted information for adverse drug events, at-risk conditions,
      and susceptible populations from black box warning labels on this site. The
      precision, recall, and F-score were, 94%, 52%, 0.67 for adverse drug events; 80%,
      53%, and 0.64 for conditions; and 95%, 44%, 0.61 for populations. Overall
      performance was 90% precision, 51% recall, and 0.65 F-Score. Information
      extracted can be stored in a structured format and may support clinical decision
      support systems. 

PMID- 25954349
TI  - Information Requirements for Health Information Exchange Supported Communication
      between Emergency Departments and Poison Control Centers.
AB  - We analyzed audio recordings of telephone calls between emergency departments
      (EDs) and poison control centers (PCCs) in order to describe the information
      requirements for health information exchange. Analysis included a random sample
      of 120 poison exposure cases involving ED-PCC communication that occurred during
      2009. We identified 52 information types characterized as patient or provider
      information, exposure information, ED assessment and treatment/ management, or
      PCC consultation. These information types constitute a focused subset of
      information that should be shared in the context of emergency treatment for
      poison exposure. Up to 60% of the information types identified in the analysis of
      call recordings can be represented using existing clinical terminology. In order
      to accomplish standards-based health information exchange between EDs and PCCs
      using data coded according to a standard clinical terminology system, it is
      necessary to define appropriate terms, information models and value sets. 

PMID- 25954350
TI  - An Analysis of Medication Adherence of Sooner Health Access Network SoonerCare
      Choice Patients.
AB  - Medication adherence is a desirable but rarely available metric in patient care,
      providing key insights into patient behavior that has a direct effect on a
      patient's health. In this research, we determine the medication adherence
      characteristics of over 46,000 patients enrolled in the Sooner Health Access
      Network (HAN), based on Medicaid claims data from the Oklahoma Health Care
      Authority. We introduce a new measure called Specific Medication PDC (smPDC),
      based on the popular Proportion of Days Covered (PDC) method, using the last fill
      date for the end date of the measurement duration. The smPDC method is
      demonstrated by calculating medication adherence across the eligible patient
      population, for relevant subpopulations over a two-year period spanning 2012 -
      2013. We leverage a clinical analytics platform to disseminate adherence
      measurements to providers. Aggregate results demonstrate that the smPDC method is
      relevant and indicates potential opportunities for health improvement for certain
      population segments. 

PMID- 25954351
TI  - Sophia: A Expedient UMLS Concept Extraction Annotator.
AB  - An opportunity exists for meaningful concept extraction and indexing from large
      corpora of clinical notes in the Veterans Affairs (VA) electronic medical record.
      Currently available tools such as MetaMap, cTAKES and HITex do not scale up to
      address this big data need. Sophia, a rapid UMLS concept extraction annotator was
      developed to fulfill a mandate and address extraction where high throughput is
      needed while preserving performance. We report on the development, testing and
      benchmarking of Sophia against MetaMap and cTAKEs. Sophia demonstrated improved
      performance on recall as compared to cTAKES and MetaMap (0.71 vs 0.66 and 0.38).
      The overall f-score was similar to cTAKES and an improvement over MetaMap (0.53
      vs 0.57 and 0.43). With regard to speed of processing records, we noted Sophia to
      be several fold faster than cTAKES and the scaled-out MetaMap service. Sophia
      offers a viable alternative for high-throughput information extraction tasks. 

PMID- 25954352
TI  - Development of iBsafe: A Collaborative, Theory-based Approach to Creating a
      Mobile Game Application for Child Safety.
AB  - Unintentional injury is a leading cause of death worldwide, and the number one
      cause of child death in the United States. The American Academy of Pediatrics
      promotes safety recommendations to decrease child injury risk, however the
      majority of educational programs delivering these strategies are school-based or
      in community campaigns. Mobile technology provides an opportune platform to
      deliver pediatric injury prevention programs given its massive global reach and
      underrepresentation within the current mobile health market. This paper describes
      the development of iBsafe, a novel mobile safety game application designed to
      prevent injury in 5- to 6- year old children. Our multidisciplinary team utilized
      a step-wise approach to create an innovative child game application which is
      based in behavioral theory and promotes evidence-based safety recommendations.
      Results and future directions for iBsafe aim to interactively educate children on
      how to be safe and ultimately improve their safety behaviors. 

PMID- 25954353
TI  - Participatory Design and Development of a Patient-centered Toolkit to Engage
      Hospitalized Patients and Care Partners in their Plan of Care.
AB  - Patient engagement has been identified as a key strategy for improving patient
      outcomes. In this paper, we describe the development and pilot testing of a web
      based patient centered toolkit (PCTK) prototype to improve access to health
      information and to engage hospitalized patients and caregivers in the plan of
      care. Individual and group interviews were used to identify plan of care
      functional and workflow requirements and user interface design enhancements.
      Qualitative methods within a participatory design approach supported the
      development of a PCTK prototype that will be implemented on intensive care and
      oncology units to engage patients and professional care team members developing
      their plan of care during an acute hospitalization. 

PMID- 25954354
TI  - Evaluation of need for ontologies to manage domain content for the Reportable
      Conditions Knowledge Management System.
AB  - The Reportable Condition Knowledge Management System (RCKMS) is envisioned to be
      a single, comprehensive, authoritative, real-time portal to author, view and
      access computable information about reportable conditions. The system is designed
      for use by hospitals, laboratories, health information exchanges, and providers
      to meet public health reporting requirements. The RCKMS Knowledge Representation
      Workgroup was tasked to explore the need for ontologies to support RCKMS
      functionality. The workgroup reviewed relevant projects and defined criteria to
      evaluate candidate knowledge domain areas for ontology development. The use of
      ontologies is justified for this project to unify the semantics used to describe
      similar reportable events and concepts between different jurisdictions and over
      time, to aid data integration, and to manage large, unwieldy datasets that
      evolve, and are sometimes externally managed. 

PMID- 25954355
TI  - The Number Needed to Remind: a Measure for Assessing CDS Effectiveness.
AB  - BACKGROUND: Clinical decision support (CDS) is associated with improvement in
      quality and efficiency in healthcare delivery. The appropriate way to evaluate
      its effectiveness remains uncertain. METHODS: We analyzed data from our
      electronic health record (EHR) measuring the display frequency of eight reminders
      for Coronary Artery disease and Type 2 Diabetes and their associated performance
      according to a predefined methodology. We propose two key performance indicators
      to measure their impact on a target population: the reminder performance (RP),
      and the number needed to remind (NNR), to evaluate the impact that Clinical
      decision support reminders have on the adherence to guideline derived CDS
      interventions on the entire patient population, and individual providers
      receiving the interventions. RESULTS: Data were available for 116,027 patients
      and a total of 1,982,735 reminders were displayed to a subset of 65,516 patients
      during the study period from January 1 to December 31, 2010. The evaluation
      framework assessed provider acknowledgement of the CDS intervention, and the
      presence of the expected performance event while accounting for patients'
      exposure to the CDS reminders. The total RP was 2.7% while the average NNR was
      3.1 for all the reminders under study. CONCLUSIONS: The proposed framework to
      asses of CDS performance provides a novel approach to improve the design and
      evaluation of CDS interventions. The application of this methodology represents
      an indicator to understand the impact of CDS interventions and subsequent patient
      outcomes. Further research is required to evaluate the impact of these systems on
      the quality of care.

PMID- 25954356
TI  - Characterizing the sublanguage of online breast cancer forums for medications,
      symptoms, and emotions.
AB  - Online health communities play an increasingly prevalent role for patients and
      are the source of a growing body of research. A lexicon that represents the
      sublanguage of an online community is an important resource to enable analysis
      and tool development over this data source. This paper investigates a method to
      generate a lexicon representative of the language of members in a given community
      with respect to specific semantic types. We experiment with a breast cancer
      community and detect terms that belong to three semantic types: medications,
      symptoms and side effects, and emotions. We assess the ability of our
      automatically generated lexicons to detect new terms, and show that a data-driven
      approach captures the sublanguage of members in these communities, all the while
      increasing coverage of general-purpose terminologies. The code and the generated
      lexicons are made available to the research community. 

PMID- 25954357
TI  - Integrated multisystem analysis in a mental health and criminal justice
      ecosystem.
AB  - Patients with a serious mental illness often receive care that is fragmented due
      to reduced availability of or access to resources, and inadequate, discontinuous,
      and uncoordinated care across health, social services, and criminal justice
      organizations. These gaps in care may lead to increased mental health disease
      burden and relapse, as well as repeated incarcerations. Further, the complex
      health, social service, and criminal justice ecosystem within which the patient
      may be embedded makes it difficult to examine the role of modifiable risk factors
      and delivered services on patient outcomes, particularly given that agencies
      often maintain isolated sets of relevant data. Here we describe an approach to
      creating a multisystem analysis that derives insights from an integrated data set
      including patient access to case management services, medical services, and
      interactions with the criminal justice system. We combined data from electronic
      systems within a US mental health ecosystem that included mental health and
      substance abuse services, as well as data from the criminal justice system. We
      applied Cox models to test the associations between delivery of services and re
      incarceration. Using this approach, we found an association between arrests and
      crisis stabilization services in this population. We also found that delivery of
      case management or medical services provided after release from jail was
      associated with a reduced risk for re-arrest. Additionally, we used machine
      learning to train and validate a predictive model linking non-modifiable and
      modifiable risk factors and outcomes. A predictive model, constructed using
      elastic net regularized logistic regression, and considering age, past arrests,
      mental health diagnosis, as well as use of a jail diversion program, outpatient,
      medical and case management services predicted the probability of re-arrests with
      fair accuracy (AUC=.67). By modeling the complex interactions between risk
      factors, service delivery and outcomes, we may better enable systems of care to
      meet patient needs and improve outcomes. 

PMID- 25954359
TI  - Predicting electrocardiogram and arterial blood pressure waveforms with different
      Echo State Network architectures.
AB  - Alarm fatigue caused by false alarms and alerts is an extremely important issue
      for the medical staff in Intensive Care Units. The ability to predict
      electrocardiogram and arterial blood pressure waveforms can potentially help the
      staff and hospital systems better classify a patient's waveforms and subsequent
      alarms. This paper explores the use of Echo State Networks, a specific type of
      neural network for mining, understanding, and predicting electrocardiogram and
      arterial blood pressure waveforms. Several network architectures are designed and
      evaluated. The results show the utility of these echo state networks,
      particularly ones with larger integrated reservoirs, for predicting
      electrocardiogram waveforms and the adaptability of such models across
      individuals. The work presented here offers a unique approach for understanding
      and predicting a patient's waveforms in order to potentially improve alarm
      generation. We conclude with a brief discussion of future extensions of this
      research. 

PMID- 25954358
TI  - TagLine: Information Extraction for Semi-Structured Text in Medical Progress
      Notes.
AB  - Statistical text mining and natural language processing have been shown to be
      effective for extracting useful information from medical documents. However,
      neither technique is effective at extracting the information stored in semi
      structure text elements. A prototype system (TagLine) was developed to extract
      information from the semi-structured text using machine learning and a rule based
      annotator. Features for the learning machine were suggested by prior work, and by
      examining text, and selecting attributes that help distinguish classes of text
      lines. Classes were derived empirically from text and guided by an ontology
      developed by the VHA's Consortium for Health Informatics Research (CHIR).
      Decision trees were evaluated for class predictions on 15,103 lines of text
      achieved an overall accuracy of 98.5 percent. The class labels applied to the
      lines were then used for annotating semi-structured text elements. TagLine
      achieved F-measure over 0.9 for each of the structures, which included tables,
      slots and fillers. 

PMID- 25954360
TI  - Evaluation of RxNorm for Medication Clinical Decision Support.
AB  - We evaluated the potential use of RxNorm to provide standardized representations
      of generic drug name and route of administration to facilitate management of drug
      lists for clinical decision support (CDS) rules. We found a clear representation
      of generic drug name but not route of administration. We identified several
      issues related to data quality, including erroneous or missing defined
      relationships, and the use of different concept hierarchies to represent the same
      drug. More importantly, we found extensive semantic precoordination of orthogonal
      concepts related to route and dose form, which would complicate the use of RxNorm
      for drug-based CDS. This study demonstrated that while RxNorm is a valuable
      resource for the standardization of medications used in clinical practice,
      additional work is required to enhance the terminology so that it can support
      expanded use cases, such as managing drug lists for CDS. 

PMID- 25954361
TI  - Coverage of rare disease names in standard terminologies and implications for
      patients, providers, and research.
AB  - Small numbers of patients are a special challenge for rare diseases research.
      Electronic health record (EHR) data can facilitate research if patients with rare
      diseases can be reliably identified. We estimate the coverage of the names of a
      set of 6,519 rare diseases. Using the UMLS, 697 (11%) diseases were matched to
      ICD-9-CM, 1,386 (21%) to ICD-10-CM and 2,848 (44%) to SNOMED CT. Using published
      mappings from SNOMED CT to ICD, we further estimate additional broader matches of
      2,569 (39%) rare diseases to ICD-9-CM and 1,635 (25%) to ICD-10-CM. The number of
      codes that match one and only one disease are 1,081 (62%) for ICD-9-CM, 1,403
      (73%) for ICD-10-CM, and 3,311 (85%) for SNOMED CT. Our findings confirm that
      SNOMED CT has the greatest coverage and specificity needed to identify patients
      with a rare disease from EHR-data, and can facilitate research and evidence-based
      care. 

PMID- 25954362
TI  - Validating Health Information Exchange (HIE) Data For Quality Measurement Across
      Four Hospitals.
AB  - Health information exchange (HIE) provides an essential enhancement to electronic
      health records (EHR), allowing information to follow patients across provider
      organizations. There is also an opportunity to improve public health
      surveillance, quality measurement, and research through secondary use of HIE
      data, but data quality presents potential barriers. Our objective was to validate
      the secondary use of HIE data for two emergency department (ED) quality measures:
      identification of frequent ED users and early (72-hour) ED returns. We compared
      concordance of various demographic and encounter data from an HIE for four
      hospitals to data provided by the hospitals from their EHRs over a two year
      period, and then compared measurement of our two quality measures using both HIE
      and EHR data. We found that, following data cleaning, there was no significant
      difference in the total counts for frequent ED users or early ED returns for any
      of the four hospitals (p<0.001). 

PMID- 25954363
TI  - An evaluation of a natural language processing tool for identifying and encoding
      allergy information in emergency department clinical notes.
AB  - Emergency department (ED) visits due to allergic reactions are common. Allergy
      information is often recorded in free-text provider notes; however, this domain
      has not yet been widely studied by the natural language processing (NLP)
      community. We developed an allergy module built on the MTERMS NLP system to
      identify and encode food, drug, and environmental allergies and allergic
      reactions. The module included updates to our lexicon using standard
      terminologies, and novel disambiguation algorithms. We developed an annotation
      schema and annotated 400 ED notes that served as a gold standard for comparison
      to MTERMS output. MTERMS achieved an F-measure of 87.6% for the detection of
      allergen names and no known allergies, 90% for identifying true reactions in each
      allergy statement where true allergens were also identified, and 69% for linking
      reactions to their allergen. These preliminary results demonstrate the
      feasibility using NLP to extract and encode allergy information from clinical
      notes. 

PMID- 25954364
TI  - Extracting Concepts Related to Homelessness from the Free Text of VA Electronic
      Medical Records.
AB  - Mining the free text of electronic medical records (EMR) using natural language
      processing (NLP) is an effective method of extracting information not always
      captured in administrative data. We sought to determine if concepts related to
      homelessness, a non-medical condition, were amenable to extraction from the EMR
      of Veterans Affairs (VA) medical records. As there were no off-the-shelf
      products, a lexicon of terms related to homelessness was created. A corpus of
      free text documents from outpatient encounters was reviewed to create the
      reference standard for NLP training and testing. V3NLP Framework was used to
      detect instances of lexical terms and was compared to the reference standard.
      With a positive predictive value of 77% for extracting relevant concepts, this
      study demonstrates the feasibility of extracting positively asserted concepts
      related to homelessness from the free text of medical records. 

PMID- 25954365
TI  - Integrating public data sets for analysis of maternal airborne environmental
      exposures and stillbirth.
AB  - Efforts to study relationships between maternal airborne pollutant exposures and
      poor pregnancy outcomes have been frustrated by data limitations. Our objective
      was to report the proportion of Ohio women in 2006-2010 experiencing stillbirth
      whose pregnancy exposure to six criteria airborne pollutants could be
      approximated by applying a geospatial approach to vital records and Environmental
      Protection Agency air monitoring data. In addition, we characterized clinical and
      socio-demographic differences among women who lived within 10 km of monitoring
      stations compared to women who did not live within proximity of monitoring
      stations. For women who experienced stillbirth, 10.8% listed a residence within
      10 km of each type of monitoring station. Maternal race, education, and marital
      status were significantly different (p<0.0001) comparing those within proximity
      to monitoring stations to those outside of monitoring range. No significant
      differences were identified in maternal age, ethnicity, smoking status,
      hypertension, or diabetes between groups. 

PMID- 25954366
TI  - Using Anchors to Estimate Clinical State without Labeled Data.
AB  - We present a novel framework for learning to estimate and predict clinical state
      variables without labeled data. The resulting models can used for electronic
      phenotyping, triggering clinical decision support, and cohort selection. The
      framework relies on key observations which we characterize and term "anchor
      variables". By specifying anchor variables, an expert encodes a certain amount of
      domain knowledge about the problem while the rest of learning proceeds in an
      unsupervised manner. The ability to build anchors upon standardized ontologies
      and the framework's ability to learn from unlabeled data promote generalizability
      across institutions. We additionally develop a user interface to enable experts
      to choose anchor variables in an informed manner. The framework is applied to
      electronic medical record-based phenotyping to enable real-time decision support
      in the emergency department. We validate the learned models using a prospectively
      gathered set of gold-standard responses from emergency physicians for nine
      clinically relevant variables. 

PMID- 25954367
TI  - What Is Asked in Clinical Data Request Forms? A Multi-site Thematic Analysis of
      Forms Towards Better Data Access Support.
AB  - Many academic medical centers have aggregated data from multiple clinical systems
      into centralized repositories. These repositories can then be queried by skilled
      data analysts who act as intermediaries between the data stores and the research
      teams. To obtain data, researchers are often expected to complete a data request
      form. Such forms are meant to support record-keeping and, most importantly,
      provide a means for conveying complex data needs in a clear and understandable
      manner. Yet little is known about how data request forms are constructed and how
      effective they are likely to be. We conducted a content analysis of ten data
      request forms from CTSA-supported institutions. We found that most of the forms
      over-emphasized the collection of metadata that were not considered germane to
      the actual data needs. Based on our findings, we provide recommendations to
      improve the quality of data request forms in support of clinical and
      translational research. 

PMID- 25954368
TI  - Evaluating health interest profiles extracted from patient-generated data.
AB  - Patient-generated health data (PGHD) offers a promising resource for shaping
      patient care, self-management, population health, and health policy. Although
      emerging technologies bolster opportunities to extract PGHD and profile the needs
      and experiences of patients, few efforts examine the validity and use of such
      profiles from the patient's perspective. To address this gap, we explore health
      interest profiles built automatically from online community posts. Through a user
      evaluation with community members, we found that extracted profiles not only
      align with members' stated health interests, but also expand upon those manually
      entered interests with little user effort. Community members express positive
      attitudes toward the use and expansion of profiles to connect with peers for
      support. Despite this promising approach, findings also point to improvements
      required of biomedical text processing tools to effectively process PGHD.
      Findings demonstrate opportunities to leverage the wealth of unstructured PGHD
      available in emerging technologies that patients regularly use. 

PMID- 25954369
TI  - Developing a section labeler for clinical documents.
AB  - Natural language processing (NLP) technologies provide an opportunity to extract
      key patient data from free text documents within the electronic health record
      (EHR). We are developing a series of components from which to construct NLP
      pipelines. These pipelines typically begin with a component whose goal is to
      label sections within medical documents with codes indicating the anticipated
      semantics of their content. This Clinical Section Labeler prepares the document
      for further, focused information extraction. Below we describe the evaluation of
      six algorithms designed for use in a Clinical Section Labeler. These algorithms
      are trained with N-gram-based feature sets extracted from document sections and
      the document types. In the evaluation, 6 different Bayesian models were trained
      and used to assign one of 27 different topics to each section. A tree-augmented
      Bayesian network using the document type and N-grams derived from section headers
      proved most accurate in assigning individual sections appropriate section topics.

PMID- 25954370
TI  - Security Concerns in Android mHealth Apps.
AB  - Mobile Health (mHealth) applications lie outside of regulatory protection such as
      HIPAA, which requires a baseline of privacy and security protections appropriate
      to sensitive medical data. However, mHealth apps, particularly those in the app
      stores for iOS and Android, are increasingly handling sensitive data for both
      professionals and patients. This paper presents a series of three studies of the
      mHealth apps in Google Play that show that mHealth apps make widespread use of
      unsecured Internet communications and third party servers. Both of these
      practices would be considered problematic under HIPAA, suggesting that increased
      use of mHealth apps could lead to less secure treatment of health data unless
      mHealth vendors make improvements in the way they communicate and store data. 

PMID- 25954371
TI  - Fostering Multilinguality in the UMLS: A Computational Approach to Terminology
      Expansion for Multiple Languages.
AB  - We here report on efforts to computationally support the maintenance and
      extension of multilingual biomedical terminology resources. Our main idea is to
      treat term acquisition as a classification problem guided by term alignment in
      parallel multilingual corpora, using termhood information coming from of a named
      entity recognition system as a novel feature. We report on experiments for
      Spanish, French, German and Dutch parts of a multilingual UMLS-derived biomedical
      terminology. These efforts yielded 19k, 18k, 23k and 12k new terms and synonyms,
      respectively, from which about half relate to concepts without a previously
      available term label for these non-English languages. Based on expert assessment
      of a novel German terminology sample, 80% of the newly acquired terms were judged
      as reasonable additions to the terminology. 

PMID- 25954372
TI  - Problem management module: an innovative system to improve problem list workflow.
AB  - Electronic problem lists are essential to modern health record systems, with a
      primary goal to serve as the repository of a patient's current health issues.
      Additionally, coded problems can be used to drive downstream activities such as
      decision support, evidence-based medicine, billing, and cohort generation for
      research. Meaningful Use also requires use of a coded problem list. Over the
      course of three years, Intermountain Healthcare developed a problem management
      module (PMM) that provided innovative functionality to improve clinical workflow
      and boost problem list adoption, e.g. smart search, user customizable views,
      problem evolution, and problem timelines. In 23 months of clinical use,
      clinicians entered over 70,000 health issues, the percentage of free-text items
      dropped to 1.2%, completeness of problem list items increased by 14%, and more
      collaborative habits were initiated. 

PMID- 25954373
TI  - Reasoning based quality assurance of medical ontologies: a case study.
AB  - The World Health Organisation is using OWL as a key technology to develop ICD-11 
      the next version of the well-known International Classification of Diseases.
      Besides providing better opportunities for data integration and linkages to other
      well-known ontologies such as SNOMED-CT, one of the main promises of using OWL is
      that it will enable various forms of automated error checking. In this paper we
      investigate how automated OWL reasoning, along with a Justification Finding
      Service can be used as a Quality Assurance technique for the development of large
      and complex ontologies such as ICD-11. Using the International Classification of
      Traditional Medicine (ICTM) - Chapter 24 of ICD-11 - as a case study, and an
      expert panel of knowledge engineers, we reveal the kinds of problems that can
      occur, how they can be detected, and how they can be fixed. Specifically, we
      found that a logically inconsistent version of the ICTM ontology could be
      repaired using justifications (minimal entailing subsets of an ontology).
      Although over 600 justifications for the inconsistency were initially computed,
      we found that there were three main manageable patterns or categories of
      justifications involving TBox and ABox axioms. These categories represented
      meaningful domain errors to an expert panel of ICTM project knowledge engineers,
      who were able to use them to successfully determine the axioms that needed to be
      revised in order to fix the problem. All members of the expert panel agreed that
      the approach was useful for debugging and ensuring the quality of ICTM. 

PMID- 25954374
TI  - Coordination of care for complex pediatric patients: perspectives from providers
      and parents.
AB  - Coordinators help patients requiring complex chronic care manage frequent
      ambulatory visits and services received at home or from community-based agencies.
      EHRs directly support only a few of the required tasks as they do not allow
      access to all parties involved in care. Our goal was to examine how technology
      was used to coordinate efforts and to describe common barriers and facilitators.
      Insights may inform the design of tools that would effectively support identified
      goals. We conducted five hours of interviews with sixteen parents and six
      clinicians and characterized emergent themes from transcripts. Situational
      awareness, care and visit planning, document aggregation, abstraction and
      interpretation were tasks essential to coordination yet generally poorly
      supported by EHRs. Providers communicated primarily by email, telephone and by
      exchanging paper and scanned documents. A preliminary model of coordination that
      could be used in the planning and testing stages of a User Centered Design
      process is described. 

PMID- 25954375
TI  - Effect of obesity and clinical factors on pre-incision time: study of operating
      room workflow.
AB  - As the obese population is increasing rapidly worldwide, there is more interest
      to study the different aspects of obesity and its impact especially on healthcare
      outcomes and health related issues. Targeting non-surgical times in the operating
      room (OR), this study focuses on the effect of obesity along with clinical
      factors on pre-incision times in OR. Specifically, both the individual and
      combined effect of clinical factors with obesity on pre-incision times is
      studied. Results show that with the confidence of 95%, pre-incision time in the
      OR of obese patients is significantly higher than those for non-obese patients by
      approximately five percent. Findings also show that more complex cases do not
      exhibit significant differences between these patient subgroups. 

PMID- 25954376
TI  - Enabling locally-developed content for access through the infobutton by means of
      automated concept annotation.
AB  - Infobuttons have proven to be an increasingly important resource in providing a
      standardized approach to integrating useful educational materials at the point of
      care in electronic health records (EHRs). They provide a simple, uniform pathway
      for both patients and providers to receive pertinent education materials in a
      quick fashion from within EHRs and Personalized Health Records (PHRs). In recent
      years, the international standards organization Health Level Seven has balloted
      and approved a standards-based pathway for requesting and receiving data for
      infobuttons, simplifying some of the barriers for their adoption in electronic
      medical records and amongst content providers. Local content, developed by the
      hosting organization themselves, still needs to be indexed and annotated with
      appropriate metadata and terminologies in order to be fully accessible via the
      infobutton. In this manuscript we present an approach for automating the
      annotation of internally-developed patient education sheets with standardized
      terminologies and compare and contrast the approach with manual approaches used
      previously. We anticipate that a combination of system-generated and human
      reviewed annotations will provide the most comprehensive and effective indexing
      strategy, thereby allowing best access to internally-created content via the
      infobutton. 

PMID- 25954377
TI  - Disease progression subtype discovery from longitudinal EMR data with a majority
      of missing values and unknown initial time points.
AB  - Electronic medical records (EMR) contain a longitudinal collection of laboratory
      data that contains valuable phenotypic information on disease progression of a
      large collection of patients. These data can be potentially used in medical
      research or patient care; finding disease progression subtypes is a particularly
      important application. There are, however, two significant difficulties in
      utilizing this data for statistical analysis: (a) a large proportion of data is
      missing and (b) patients are in very different stages of disease progression and
      there are no well-defined start points of the time series. We present a Bayesian
      machine learning model that overcomes these difficulties. The method can use
      highly incomplete time-series measurement of varying lengths, it aligns together
      similar trajectories in different phases and is capable of finding consistent
      disease progression subtypes. We demonstrate the method on finding chronic kidney
      disease progression subtypes. 

PMID- 25954378
TI  - Piloting a deceased subject integrated data repository and protecting privacy of
      relatives.
AB  - Use of deceased subject Electronic Health Records can be an important piloting
      platform for informatics or biomedical research. Existing legal framework allows
      such research under less strict de-identification criteria; however, privacy of
      non-decedent must be protected. We report on creation of the decease subject
      Integrated Data Repository (dsIDR) at National Institutes of Health, Clinical
      Center and a pilot methodology to remove secondary protected health information
      or identifiable information (secondary PxI; information about persons other than
      the primary patient). We characterize available structured coded data in dsIDR
      and report the estimated frequencies of secondary PxI, ranging from 12.9%
      (sensitive token presence) to 1.1% (using stricter criteria). Federating decedent
      EHR data from multiple institutions can address sample size limitations and our
      pilot study provides lessons learned and methodology that can be adopted by other
      institutions. 

PMID- 25954379
TI  - TextHunter--A User Friendly Tool for Extracting Generic Concepts from Free Text
      in Clinical Research.
AB  - Observational research using data from electronic health records (EHR) is a
      rapidly growing area, which promises both increased sample size and data richness
      - therefore unprecedented study power. However, in many medical domains, large
      amounts of potentially valuable data are contained within the free text clinical
      narrative. Manually reviewing free text to obtain desired information is an
      inefficient use of researcher time and skill. Previous work has demonstrated the
      feasibility of applying Natural Language Processing (NLP) to extract information.
      However, in real world research environments, the demand for NLP skills outweighs
      supply, creating a bottleneck in the secondary exploitation of the EHR. To
      address this, we present TextHunter, a tool for the creation of training data,
      construction of concept extraction machine learning models and their application
      to documents. Using confidence thresholds to ensure high precision (>90%), we
      achieved recall measurements as high as 99% in real world use cases. 

PMID- 25954380
TI  - Analysis of online information searching for cardiovascular diseases on a
      consumer health information portal.
AB  - Since the early 2000's, Internet usage for health information searching has
      increased significantly. Studying search queries can help us to understand users
      "information need" and how do they formulate search queries ("expression of
      information need"). Although cardiovascular diseases (CVD) affect a large
      percentage of the population, few studies have investigated how and what users
      search for CVD. We address this knowledge gap in the community by analyzing a
      large corpus of 10 million CVD related search queries from MayoClinic.com. Using
      UMLS MetaMap and UMLS semantic types/concepts, we developed a rule-based approach
      to categorize the queries into 14 health categories. We analyzed structural
      properties, types (keyword-based/Wh-questions/Yes-No questions) and linguistic
      structure of the queries. Our results show that the most searched health
      categories are 'Diseases/Conditions', 'Vital-Sings', 'Symptoms' and 'Living
      with'. CVD queries are longer and are predominantly keyword-based. This study
      extends our knowledge about online health information searching and provides
      useful insights for Web search engines and health websites. 

PMID- 25954381
TI  - Characterization of a handoff documentation tool through usage log data.
AB  - Handoffs are a critical component of coordinated patient care; however, poor
      handoffs have been associated with near misses and adverse events. To address
      this, national agencies have recommended standardizing handoffs, for example
      through the use of handoff documentation tools. Recent research suggests that
      handoff tools, typically designed for physicians, are often used by non-physician
      providers as information sources. In this study, we investigated patterns of
      edits of an electronic handoff tool in a large teaching hospital through
      examination of its usage log data. Qualitative interviews with clinicians were
      used to triangulate log data findings. The analysis showed that despite its
      primary focus on facilitating transitions of care, information in the handoff
      documentation tool was updated throughout the day. Interviews with residents
      confirmed that they purposefully updated information to make it available for
      other members of their patient care teams. This further reiterates the view of
      electronic handoff tools as facilitators of team communication and coordination.
      However, the study also showed considerable variability in the frequency of
      updates between different units and across different patients. Further research
      is required to understand what factors drive such diversity in the use of
      electronic handoff tool and whether this diversity can be used to make inferences
      about patients' conditions. 

PMID- 25954382
TI  - An automated approach for ranking journals to help in clinician decision support.
AB  - Point of care access to knowledge from full text journal articles supports
      decision-making and decreases medical errors. However, it is an overwhelming task
      to search through full text journal articles and find quality information needed
      by clinicians. We developed a method to rate journals for a given clinical topic,
      Congestive Heart Failure (CHF). Our method enables filtering of journals and
      ranking of journal articles based on source journal in relation to CHF. We also
      obtained a journal priority score, which automatically rates any journal based on
      its importance to CHF. Comparing our ranking with data gathered by surveying 169
      cardiologists, who publish on CHF, our best Multiple Linear Regression model
      showed a correlation of 0.880, based on five-fold cross validation. Our ranking
      system can be extended to other clinical topics. 

PMID- 25954383
TI  - De-identification of Address, Date, and Alphanumeric Identifiers in Narrative
      Clinical Reports.
AB  - INTRODUCTION: The Privacy Rule of Health Insurance Portability and Accountability
      Act requires that clinical documents be stripped of personally identifying
      information before they can be released to researchers and others. We have been
      developing a software application, NLM Scrubber, to de-identify narrative
      clinical reports. METHODS: We compared NLM Scrubber with MIT's and MITRE's de
      identification systems on 3,093 clinical reports about 1,636 patients. The
      performance of each system was analyzed on address, date, and alphanumeric
      identifier recognition separately. Their overall performance on de-identification
      and on conservation of the remaining clinical text was analyzed as well. RESULTS:
      NLM Scrubber's sensitivity on de-identifying these identifiers was 99%. It's
      specificity on conserving the text with no personal identifiers was 99% as well.
      CONCLUSION: The current version of the system recognizes and redacts patient
      names, alphanumeric identifiers, addresses and dates. We plan to make the system
      available prior to the AMIA Annual Symposium in 2014.

PMID- 25954384
TI  - Engineering for reliability in at-home chronic disease management.
AB  - Individuals with chronic conditions face challenges with maintaining lifelong
      adherence to self-management activities. Although reminders can help support the
      cognitive demands of managing daily and future health tasks, we understand little
      of how they fit into people's daily lives. Utilizing a maximum variation sampling
      method, we interviewed and compared the experiences of 20 older adults with
      diabetes and 19 mothers of children with asthma to understand reminder use for at
      home chronic disease management. Based on our participants' experiences, we
      contend that many self-management failures should be viewed as systems failures,
      rather than individual failures and non-compliance. Furthermore, we identify key
      principles from reliability engineering that both explain current behavior and
      suggest strategies to improve patient reminder systems. 

PMID- 25954385
TI  - Automatic extraction of drug indications from FDA drug labels.
AB  - Extracting computable indications, i.e. drug-disease treatment relationships,
      from narrative drug resources is the key for building a gold standard drug
      indication repository. The two steps to the extraction problem are disease named
      entity recognition (NER) to identify disease mentions from a free-text
      description and disease classification to distinguish indications from other
      disease mentions in the description. While there exist many tools for disease
      NER, disease classification is mostly achieved through human annotations. For
      example, we recently resorted to human annotations to prepare a corpus,
      LabeledIn, capturing structured indications from the drug labels submitted to FDA
      by pharmaceutical companies. In this study, we present an automatic end-to-end
      framework to extract structured and normalized indications from FDA drug labels.
      In addition to automatic disease NER, a key component of our framework is a
      machine learning method that is trained on the LabeledIn corpus to classify the
      NER-computed disease mentions as "indication vs. non-indication." Through
      experiments with 500 drug labels, our end-to-end system delivered 86.3% F1
      measure in drug indication extraction, with 17% improvement over baseline.
      Further analysis shows that the indication classifier delivers a performance
      comparable to human experts and that the remaining errors are mostly due to
      disease NER (more than 50%). Given its performance, we conclude that our end-to
      end approach has the potential to significantly reduce human annotation costs. 

PMID- 25954386
TI  - Applications of health information exchange information to public health
      practice.
AB  - Increased information availability, timeliness, and comprehensiveness through
      health information exchange (HIE) can support public health practice. The
      potential benefits to disease monitoring, disaster response, and other public
      health activities served as an important justification for the US' investments in
      HIE. After several years of HIE implementation and funding, we sought to
      determine if any of the anticipated benefits of exchange participation were
      accruing to state and local public health practitioners participating in five
      different exchanges. Using qualitative interviews and template analyses, we
      identified public health efforts and activities that were improved by
      participation in HIE. HIE supported public health activities consistent with
      expectations in the literature. However, no single department realized all the
      potential benefits of HIE identified. These findings suggest ways to improve HIE
      usage in public health. 

PMID- 25954387
TI  - Trends in publication of nursing informatics research.
AB  - We analyzed 741 journal articles on nursing informatics published in 7
      biomedical/nursing informatics journals and 6 nursing journals from 2005 to 2013
      to begin to understand publication trends in nursing informatics research and
      identify gaps. We assigned a research theme to each article using AMIA 2014 theme
      categories and normalized the citation counts using time from publication.
      Overall, nursing informatics research covered a broad spectrum of research topics
      in biomedical informatics and publication topics seem to be well aligned with the
      high priority research agenda identified by the nursing informatics community.
      The research themes with highest volume of publication were Clinical Workflow and
      Human Factors, Consumer Informatics and Personal Health Records, and Clinical
      Informatics, for which an increasing trend in publication was noted. Articles on
      Informatics Education and Workforce Development; Data Mining, NLP, Information
      Extraction; and Clinical Informatics showed steady and high volume of citations. 

PMID- 25954388
TI  - Effectiveness of Evidence-Based Congestive Heart Failure (CHF) CPOE Order Sets
      Measured by Health Outcomes.
AB  - OBJECTIVE: Evidence-based order sets for treatment of patients with common
      conditions promise ordering efficiency and more consistent health outcomes.
      Despite ongoing utilization of order sets, quantitative evidence of their
      effectiveness is lacking. This study quantitatively analyzed benefits of CHF
      order sets as measured by mortality, readmission, and length of stay (LOS)
      outcomes. METHODS: Mortality and readmissions were analyzed by comparing "order
      set" and "free text" groups of adult patients using logistic regression, Pearson
      chi-squared, and Fisher's exact methods. LOS was calculated by applying One-Way
      ANOVA and Mann-Whitney tests, supplemented by comorbidity analysis via Charlson
      Comorbidity Index. RESULTS: CHF orders placed via sets were effective in reducing
      mortality [OR=1.818;95% CF 1.039-3.181;p=0.034] and LOS
      [F(1,10938)=8.352,p=0.013,4.75 days ("free text" group) vs. 5.46 days ("order
      set" group)], while readmission outcome was not significant [OR=0.913;95% CF
      0.734-1.137;p=0.417]. CONCLUSION: Evidence-based medication ordering practices to
      treat CHF have potential to reduce mortality and LOS, without effect on
      readmissions.

PMID- 25954389
TI  - Clinical Decision Support-based Quality Measurement (CDS-QM) Framework: Prototype
      Implementation, Evaluation, and Future Directions.
AB  - Electronic quality measurement (QM) and clinical decision support (CDS) are
      closely related but are typically implemented independently, resulting in
      significant duplication of effort. While it seems intuitive that technical
      approaches could be re-used across these two related use cases, such reuse is
      seldom reported in the literature, especially for standards-based approaches.
      Therefore, we evaluated the feasibility of using a standards-based CDS framework
      aligned with anticipated EHR certification criteria to implement electronic QM.
      The CDS-QM framework was used to automate a complex national quality measure
      (SCIP-VTE-2) at an academic healthcare system which had previously relied on time
      consuming manual chart abstractions. Compared with 305 manually-reviewed
      reference cases, the recall of automated measurement was 100%. The precision was
      96.3% (CI:92.6%-98.5%) for ascertaining the denominator and 96.2% (CI:92.3%
      98.4%) for the numerator. We therefore validated that a standards-based CDS-QM
      framework can successfully enable automated QM, and we identified benefits and
      challenges with this approach. 

PMID- 25954390
TI  - A Framework for Incorporating Patient Preferences to Deliver Participatory
      Medicine via Interdisciplinary Healthcare Teams.
AB  - Participatory medicine refers to the equal participation of patients and
      interdisciplinary healthcare team (IHT) members as part of care delivery.
      Facilitating workflow execution is a significant challenge for participatory
      medicine because of the need to integrate IHT members into a common workflow. A
      further challenge is that patient preferences should be considered when executing
      a workflow. To date there is limited research on supporting patient workflow as
      part of participatory medicine practices. To address that shortcoming we used a
      two-phase approach to develop a framework for participatory medicine that
      integrates different IHT members and workflows including the incorporation of
      patient preferences about care delivery options. Our framework uses a domain
      ontology to define the patient, IHT concepts and relations, as well as a workflow
      for operationalizing participatory medicine via an IHT. Proof of concept of the
      proposed framework is illustrated with a palliative care pain management case
      study. 

PMID- 25954391
TI  - Medical alert management: a real-time adaptive decision support tool to reduce
      alert fatigue.
AB  - With the adoption of electronic medical records (EMRs), drug safety alerts are
      increasingly recognized as valuable tools for reducing adverse drug events and
      improving patient safety. However, even with proper tuning of the EMR alert
      parameters, the volume of unfiltered alerts can be overwhelming to users. In this
      paper, we design an adaptive decision support tool in which past cognitive
      overriding decisions of users are learned, adapted and used for filtering actions
      to be performed on current alerts. The filters are designed and learned based on
      a moving time window, number of alerts, overriding rates, and monthly overriding
      fluctuations. Using alerts from two separate years to derive filters and test
      performance, predictive accuracy rates of 91.3%-100% are achieved. The moving
      time window works better than a static training approach. It allows continuous
      learning and capturing of the most recent decision characteristics and seasonal
      variations in drug usage. The decision support system facilitates filtering of
      non-essential alerts and adaptively learns critical alerts and highlights them
      prominently to catch providers' attention. The tool can be plugged into an
      existing EMR system as an add-on, allowing real-time decision support to users
      without interfering with existing EMR functionalities. By automatically filtering
      the alerts, the decision support tool mitigates alert fatigue and allows users to
      focus resources on potentially vital alerts, thus reducing the occurrence of
      adverse drug events. 

PMID- 25954393
TI  - Automatic detection of dilated cardiomyopathy in cardiac ultrasound videos.
AB  - In this paper we address the problem of automatic detection of dilated
      cardiomyopathy from cardiac ultrasound videos. Specifically, we present a new
      method of robustly locating the left ventricle by using the key idea that the
      region closest to the apex in a 4-chamber view is the left ventricular region.
      For this, we locate a region of interest containing the heart in an
      echocardiogram image using the bounding lines of the viewing sector to locate the
      apex of the heart. We then select low intensity regions as candidates, and find
      the low intensity region closest to the apex as the left ventricle. Finally, we
      refine the boundary by averaging the detection across the heart cycle using the
      successive frames of the echocardiographic video sequence. By extracting
      eigenvalues of the shape to represent the spread of the left ventricle in both
      length and width and augmenting it with pixel area, we form a small set of robust
      features to discriminate between normal and dilated left ventricles using a
      support vector machine classifier. Testing of the method of a collection of 654
      patient cases from a dataset used to train echocardiographers has revealed the
      promise of this automated approach to detecting dilated cardiomyopathy in
      echocardiography video sequences. 

PMID- 25954392
TI  - COPD Hospitalization Risk Increased with Distinct Patterns of Multiple Systems
      Comorbidities Unveiled by Network Modeling.
AB  - Earlier studies on hospitalization risk are largely based on regression models.
      To our knowledge, network modeling of multiple comorbidities is novel and
      inherently enables multidimensional scoring and unbiased feature reduction.
      Network modeling was conducted using an independent validation design starting
      from 38,695 patients, 1,446,581 visits, and 430 distinct clinical
      facilities/hospitals. Odds ratios (OR) were calculated for every pair of
      comorbidity using patient counts and compared their tendency with hospitalization
      rates and ED visits. Network topology analyses were performed, defining
      significant comorbidity associations as having OR>=5 & False-Discovery-Rate<=10(
      7). Four COPD-associated comorbidity sub-networks emerged, incorporating multiple
      clinical systems: (i) metabolic syndrome, (ii) substance abuse and mental
      disorder, (iii) pregnancy-associated conditions, and (iv) fall-related injury.
      The latter two have not been reported yet. Features prioritized from the network
      are predictive of hospitalizations in an independent set (p<0.004). Therefore, we
      suggest that network topology is a scalable and generalizable method predictive
      of hospitalization. 

PMID- 25954394
TI  - p-medicine: A Medical Informatics Platform for Integrated Large Scale
      Heterogeneous Patient Data.
AB  - Secure access to patient data is becoming of increasing importance, as medical
      informatics grows in significance, to both assist with population health studies,
      and patient specific medicine in support of treatment. However, assembling the
      many different types of data emanating from the clinic is in itself a difficulty,
      and doing so across national borders compounds the problem. In this paper we
      present our solution: an easy to use distributed informatics platform embedding a
      state of the art data warehouse incorporating a secure pseudonymisation system
      protecting access to personal healthcare data. Using this system, a whole range
      of patient derived data, from genomics to imaging to clinical records, can be
      assembled and linked, and then connected with analytics tools that help us to
      understand the data. Research performed in this environment will have immediate
      clinical impact for personalised patient healthcare. 

PMID- 25954395
TI  - U-path: An undirected path-based measure of semantic similarity.
AB  - In this paper, we present the results of a method using undirected paths to
      determine the degree of semantic similarity between two concepts in a dense
      taxonomy with multiple inheritance. The overall objective of this work was to
      explore methods that take advantage of dense multi-hierarchical taxonomies that
      are more graph-like than tree-like by incorporating the proximity of concepts
      with respect to each other within the entire is-a hierarchy. Our hypothesis is
      that the proximity of the concepts regardless of how they are connected is an
      indicator to the degree of their similarity. We evaluate our method using the
      Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT), and four
      reference standards that have been manually tagged by human annotators. The
      overall results of our experiments show, in SNOMED CT, the location of the
      concepts with respect to each other does indicate the degree to which they are
      similar. 

PMID- 25954396
TI  - First-order logic theory for manipulating clinical practice guidelines applied to
      comorbid patients: a case study.
AB  - Clinical practice guidelines (CPGs) implement evidence-based medicine designed to
      help generate a therapy for a patient suffering from a single disease. When
      applied to a comorbid patient, the concurrent combination of treatment steps from
      multiple CPGs is susceptible to adverse interactions in the resulting combined
      therapy (i.e., a therapy established according to all considered CPGs). This
      inability to concurrently apply CPGs has been shown to be one of the key
      shortcomings of CPG uptake in a clinical setting1. Several research efforts are
      underway to address this issue such as the K4CARE2 and GuideLine INteraction
      Detection Assistant (GLINDA)3 projects and our previous research on applying
      constraint logic programming to developing a consistent combined therapy for a
      comorbid patient4. However, there is no generalized framework for mitigation that
      effectively captures general characteristics of the problem while handling
      nuances such as time and ordering requirements imposed by specific CPGs. In this
      paper we propose a first-order logic-based (FOL) approach for developing a
      generalized framework of mitigation. This approach uses a meta-algorithm and
      entailment properties to mitigate (i.e., identify and address) adverse
      interactions introduced by concurrently applied CPGs. We use an illustrative case
      study of a patient suffering from type 2 diabetes being treated for an onset of
      severe rheumatoid arthritis to show the expressiveness and robustness of our
      proposed FOL-based approach, and we discuss its appropriateness as the basis for
      the generalized theory. 

PMID- 25954397
TI  - An empirically derived taxonomy of errors in SNOMED CT.
AB  - Ontologies underpin methods throughout biomedicine and biomedical informatics.
      However, as ontologies increase in size and complexity, so does the likelihood
      that they contain errors. Effective methods that identify errors are typically
      manual and expert-driven; however, automated methods are essential for the size
      of modern biomedical ontologies. The effect of ontology errors on their
      application is unclear, creating a challenge in differentiating salient, relevant
      errors with those that have no discernable effect. As a first step in
      understanding the challenge of identifying salient, common errors at a large
      scale, we asked 5 experts to verify a random subset of complex relations in the
      SNOMED CT CORE Problem List Subset. The experts found 39 errors that followed
      several common patterns. Initially, the experts disagreed about errors almost
      entirely, indicating that ontology verification is very difficult and requires
      many eyes on the task. It is clear that additional empirically-based, application
      focused ontology verification method development is necessary. Toward that end,
      we developed a taxonomy that can serve as a checklist to consult during ontology
      quality assurance. 

PMID- 25954400
TI  - Pharmacovigilance on twitter? Mining tweets for adverse drug reactions.
AB  - Recent research has shown that Twitter data analytics can have broad implications
      on public health research. However, its value for pharmacovigilance has been
      scantly studied - with health related forums and community support groups
      preferred for the task. We present a systematic study of tweets collected for 74
      drugs to assess their value as sources of potential signals for adverse drug
      reactions (ADRs). We created an annotated corpus of 10,822 tweets. Each tweet was
      annotated for the presence or absence of ADR mentions, with the span and Unified
      Medical Language System (UMLS) concept ID noted for each ADR present. Using
      Cohen's kappa1, we calculated the inter-annotator agreement (IAA) for the binary
      annotations to be 0.69. To demonstrate the utility of the corpus, we attempted a
      lexicon-based approach for concept extraction, with promising success (54.1%
      precision, 62.1% recall, and 57.8% F-measure). A subset of the corpus is freely
      available at: http://diego.asu.edu/downloads. 

PMID- 25954399
TI  - Using TURF to understand the functions of interruptions.
AB  - Interruptions are an often lamented and frequently studied aspect of clinical
      practice. However, some interruptions, such as updates on patient care decisions
      and notifications of detrimental patient lab values, are in fact necessary to the
      work process. In this paper, we explore the interruptions as an emergent feature
      of communication in teams. Looking beyond the frequency of interruptions, we
      consider the source and intent of interruptions with the goal of discovering the
      functions served by such communications. Furthermore, in this study of an
      emergency department, we classify interruptions into those activities that
      support required work and those interruptions that create unnecessary breaks in
      workflow. The intent of our larger body of work is to develop health information
      technology systems that support team efforts including the functions currently
      served by interruptions. 

PMID- 25954398
TI  - Development and validation of an electronic phenotyping algorithm for chronic
      kidney disease.
AB  - Twenty-six million Americans are estimated to have chronic kidney disease (CKD)
      with increased risk for cardiovascular disease and end stage renal disease. CKD
      is frequently undiagnosed and patients are unaware, hampering intervention. A
      tool for accurate and timely identification of CKD from electronic medical
      records (EMR) could improve healthcare quality and identify patients for
      research. As members of eMERGE (electronic medical records and genomics) Network,
      we developed an automated phenotyping algorithm that can be deployed to identify
      rapidly diabetic and/or hypertensive CKD cases and controls in health systems
      with EMRs It uses diagnostic codes, laboratory results, medication and blood
      pressure records, and textual information culled from notes. Validation
      statistics demonstrated positive predictive values of 96% and negative predictive
      values of 93.3. Similar results were obtained on implementation by two
      independent eMERGE member institutions. The algorithm dramatically outperformed
      identification by ICD-9-CM codes with 63% positive and 54% negative predictive
      values, respectively. 

PMID- 25954401
TI  - Computerization of Mental Health Integration complexity scores at Intermountain
      Healthcare.
AB  - Intermountain Healthcare's Mental Health Integration (MHI) Care Process Model
      (CPM) contains formal scoring criteria for assessing a patient's mental health
      complexity as "mild," "medium," or "high" based on patient data. The complexity
      score attempts to assist Primary Care Physicians in assessing the mental health
      needs of their patients and what resources will need to be brought to bear. We
      describe an effort to computerize the scoring. Informatics and MHI personnel
      collaboratively and iteratively refined the criteria to make them adequately
      explicit and reflective of MHI objectives. When tested on retrospective data of
      540 patients, the clinician agreed with the computer's conclusion in 52.8% of the
      cases (285/540). We considered the analysis sufficiently successful to begin
      piloting the computerized score in prospective clinical care. So far in the
      pilot, clinicians have agreed with the computer in 70.6% of the cases (24/34). 

PMID- 25954403
TI  - Examining the Multi-level Fit between Work and Technology in a Secure Messaging
      Implementation.
AB  - Secure messaging (SM) allows patients to communicate with their providers for non
      urgent health issues. Like other health information technologies, the design and
      implementation of SM should account for workflow to avoid suboptimal outcomes. SM
      may present unique workflow challenges because patients add a layer of
      complexity, as they are also direct users of the system. This study explores SM
      implementation at two Veterans Health Administration facilities. We interviewed
      twenty-nine members of eight primary care teams using semi-structured interviews.
      Questions addressed staff opinions about the integration of SM with daily
      practice, and team members' attitudes and experiences with SM. We describe the
      clinical workflow for SM, examining complexity and variability. We identified
      eight workflow issues directly related to efficiency and patient satisfaction,
      based on an exploration of the technology fit with multilevel factors. These
      findings inform organizational interventions that will accommodate SM
      implementation and lead to more patient-centered care. 

PMID- 25954404
TI  - Visualization of patient prescription history data in emergency care.
AB  - Interpreting patient's medication history from long textual data can be unwieldy
      especially in emergency care. We developed a real-time software application that
      converts one-year-long patient prescription history data into a visually
      appealing and information-rich timeline chart. The chart can be digested by
      healthcare providers quickly; hence, it could be an invaluable clinical tool when
      the rapid response time is crucial as in stroke or severe trauma cases.
      Furthermore, the visual clarity of the displayed information may help providers
      minimize medication errors. The tool has been deployed at the emergency
      department of a trauma center. Due to its popularity, we developed another
      version of this tool. It provides more granular drug dispensation information,
      which clinical pharmacists find very useful in their routine medication
      reconciliation efforts. 

PMID- 25954402
TI  - A Template for Authoring and Adapting Genomic Medicine Content in the eMERGE
      Infobutton Project.
AB  - The Electronic Medical Records and Genomics (eMERGE) Network is a national
      consortium that is developing methods and best practices for using the electronic
      health record (EHR) for genomic medicine and research. We conducted a multi-site
      survey of information resources to support integration of pharmacogenomics into
      clinical care. This work aimed to: (a) characterize the diversity of information
      resource implementation strategies among eMERGE institutions; (b) develop a
      master template containing content topics of important for genomic medicine (as
      identified by the DISCERN-Genetics tool); and (c) assess the coverage of content
      topics among information resources developed by eMERGE institutions. Given that a
      standard implementation does not exist and sites relied on a diversity of
      information resources, we identified a need for a national effort to efficiently
      produce sharable genomic medicine resources capable of being accessed from the
      EHR. We discuss future areas of work to prepare institutions to use infobuttons
      for distributing standardized genomic content. 

PMID- 25954405
TI  - Locating relevant patient information in electronic health record data using
      representations of clinical concepts and database structures.
AB  - Clinicians and clinical researchers often seek information in electronic health
      records (EHRs) that are relevant to some concept of interest, such as a disease
      or finding. The heterogeneous nature of EHRs can complicate retrieval, risking
      incomplete results. We frame this problem as the presence of two gaps: 1) a gap
      between clinical concepts and their representations in EHR data and 2) a gap
      between data representations and their locations within EHR data structures. We
      bridge these gaps with a knowledge structure that comprises relationships among
      clinical concepts (including concepts of interest and concepts that may be
      instantiated in EHR data) and relationships between clinical concepts and the
      database structures. We make use of available knowledge resources to develop a
      reproducible, scalable process for creating a knowledge base that can support
      automated query expansion from a clinical concept to all relevant EHR data. 

PMID- 25954406
TI  - Does query expansion limit our learning? A comparison of social-based expansion
      to content-based expansion for medical queries on the internet.
AB  - Searching for medical information online is a common activity. While it has been
      shown that forming good queries is difficult, Google's query suggestion tool, a
      type of query expansion, aims to facilitate query formation. However, it is
      unknown how this expansion, which is based on what others searched for, affects
      the information gathering of the online community. To measure the impact of
      social-based query expansion, this study compared it with content-based
      expansion, i.e., what is really in the text. We used 138,906 medical queries from
      the AOL User Session Collection and expanded them using Google's Autocomplete
      method (social-based) and the content of the Google Web Corpus (content-based).
      We evaluated the specificity and ambiguity of the expansion terms for trigram
      queries. We also looked at the impact on the actual results using domain
      diversity and expansion edit distance. Results showed that the social-based
      method provided more precise expansion terms as well as terms that were less
      ambiguous. Expanded queries do not differ significantly in diversity when
      expanded using the social-based method (6.72 different domains returned in the
      first ten results, on average) vs. content-based method (6.73 different domains,
      on average). 

PMID- 25954407
TI  - ARX--A Comprehensive Tool for Anonymizing Biomedical Data.
AB  - Collaboration and data sharing have become core elements of biomedical research.
      Especially when sensitive data from distributed sources are linked, privacy
      threats have to be considered. Statistical disclosure control allows the
      protection of sensitive data by introducing fuzziness. Reduction of data quality,
      however, needs to be balanced against gains in protection. Therefore, tools are
      needed which provide a good overview of the anonymization process to those
      responsible for data sharing. These tools require graphical interfaces and the
      use of intuitive and replicable methods. In addition, extensive testing,
      documentation and openness to reviews by the community are important. Existing
      publicly available software is limited in functionality, and often active support
      is lacking. We present ARX, an anonymization tool that i) implements a wide
      variety of privacy methods in a highly efficient manner, ii) provides an
      intuitive cross-platform graphical interface, iii) offers a programming interface
      for integration into other software systems, and iv) is well documented and
      actively supported. 

PMID- 25954408
TI  - Extending the HL7/LOINC Document Ontology Settings of Care.
AB  - Given federal mandates recommending document standards, increasing numbers of
      electronic clinical documents being created, and local initiatives/projects using
      clinical documents, there is a growing need to better represent clinical document
      metadata. The HL7/LOINC Document Ontology (DO) was developed to provide a
      standard representation of clinical document attributes with a multi-axis
      structure. Prior studies have demonstrated the need for extension of DO axes
      values and proposed new values for some axes, but significant gaps remain for
      representing the DO "Setting" axis. This study aimed to extend the "Setting" axis
      by combining the current values in the DO with values from 5 other sources.
      Evaluation and refinement by subject matter experts over a series of four
      iterative sessions resulted in a reorganized hierarchy with 254 additional values
      from a baseline of 20. Incorporating a comprehensive set of "Settings" in DO
      provides better representation of clinical information across the healthcare
      ecosystem. 

PMID- 25954409
TI  - Differences in nationwide cohorts of acupuncture users identified using
      structured and free text medical records.
AB  - Integrative medicine including complementary and alternative medicine (CAM) has
      become more available through mainstream health providers. Acupuncture is one of
      the most widely used CAM therapies, though its efficacy for treating various
      conditions requires further investigation. To assist with such investigations, we
      set out to identify acupuncture patient cohorts using a nationwide clinical data
      repository. Acupuncture patients were identified using both structured data and
      unstructured free text notes: 44,960 acupuncture patients were identified using
      structured data consisting of CPT codes;. Using unstructured free text clinical
      notes, we trained a support vector classifier with 86% accuracy and was able to
      identify an additional 101,628 acupuncture patients not identified through
      structured data (a 226% increase). In addition, characteristics of the patients
      identified through structured and unstructured data were compared, which show
      differences in geographic locations and medical service usage patterns. Patients
      identified with structured data displayed a consistently higher use of the
      Veterans Health Administration (VHA) medical system. 

PMID- 25954410
TI  - Development, Implementation and Use of Electronic Surveillance for Ventilator
      Associated Events (VAE) in Adults.
AB  - Mechanical ventilation provides an important, life-saving therapy for severely
      ill patients, but ventilated patients are at an increased risk for complications,
      poor outcomes, and death during hospitalization.1 The timely measurement of
      negative outcomes is important in order to identify potential issues and to
      minimize the risk to patients. The Centers for Disease Control and Prevention
      (CDC) created an algorithm for identifying Ventilator-Associated Events (VAE) in
      adult patients for reporting to the National Healthcare Safety Network (NHSN).
      Currently, the primarily manual surveillance tools require a significant amount
      of time from hospital infection prevention (IP) staff to apply and interpret.
      This paper describes the implementation of an electronic VAE tool using an
      internal clinical data repository and an internally developed electronic
      surveillance system that resulted in a reduction of labor efforts involved in
      identifying VAE at Barnes Jewish Hospital (BJH). 

PMID- 25954411
TI  - Automatically classifying question types for consumer health questions.
AB  - We present a method for automatically classifying consumer health questions. Our
      thirteen question types are designed to aid in the automatic retrieval of medical
      answers from consumer health resources. To our knowledge, this is the first
      machine learning-based method specifically for classifying consumer health
      questions. We demonstrate how previous approaches to medical question
      classification are insufficient to achieve high accuracy on this task.
      Additionally, we describe, manually annotate, and automatically classify three
      important question elements that improve question classification over previous
      techniques. Our results and analysis illustrate the difficulty of the task and
      the future directions that are necessary to achieve high-performing consumer
      health question classification. 

PMID- 25954412
TI  - Using Arden Syntax to identify registry-eligible very low birth weight neonates
      from the Electronic Health Record.
AB  - Condition-specific registries are essential resources for supporting
      epidemiological, quality improvement, and clinical trial studies. The
      identification of potentially eligible patients for a given registry often
      involves a manual process or use of ad hoc software tools. With the increased
      availability of electronic health data, such as within Electronic Health Record
      (EHR) systems, there is potential to develop healthcare standards based
      approaches for interacting with these data. Arden Syntax, which has traditionally
      been used to represent medical knowledge for clinical decision support, is one
      such standard that may be adapted for the purpose of registry eligibility
      determination. In this feasibility study, Arden Syntax was explored for its
      ability to represent eligibility criteria for a registry of very low birth weight
      neonates. The promising performance (100% recall; 97% precision) of the Arden
      Syntax approach at a single institution suggests that a standards-based
      methodology could be used to robustly identify registry-eligible patients from
      EHRs. 

PMID- 25954414
TI  - Analysis of medication and indication occurrences in clinical notes.
AB  - A medication indication is a valid reason to use medication. Comprehensive
      information on medication and its intended indications has valuable potential
      applications for patient treatments, quality improvements, and clinical decision
      support. Though there are some publicly available medication resources, this
      medication and indication information is comprised primarily of labeled uses
      approved by the FDA. Additionally, linking those medications and the
      corresponding indications is not easy to accomplish. Furthermore, research that
      analyzes actual medication and indication occurrences used in real clinical
      practice is limited. In this study, we compiled clinician-asserted medication and
      indication pairs from a large cohort of Mayo Clinic electronic medical records
      (EMRs) and normalized them to the standard forms (ie, medication to the RxNorm
      ingredient and indication to SNOMED-CT). We then analyzed medication and
      indication occurrences and compared them with the public resource in various
      ways, including off-label statistics. 

PMID- 25954413
TI  - Use of Design Science for Informing the Development of a Mobile App for Persons
      Living with HIV.
AB  - Mobile health (mHealth) technology presents opportunities to enhance chronic
      illness management, which is especially relevant for persons living with HIV
      (PLWH). Since mHealth technology comprises evolving and adaptable hardware and
      software, it provides many challenging design problems. To address this
      challenge, our methods were guided by the Information System Research (ISR)
      framework. This paper focuses on the Design Cycle of the ISR framework in which
      we used user-centered distributed information design methods and participatory
      action research methods to inform the design of a mobile application (app) for
      PLWH. In the first design session, participants (N=5) identified features that
      are optimal for meeting the treatment and management needs of PLWH. In the second
      design session, participants (N=6) were presented with findings from the first
      design session and pictures of existing apps. Findings from the Design Cycle will
      be evaluated with usability inspection methods. Using a systematic approach has
      the potential to improve mHealth functionality and use and subsequent impact. 

PMID- 25954415
TI  - Reducing wrong patient selection errors: exploring the design space of user
      interface techniques.
AB  - Wrong patient selection errors are a major issue for patient safety; from
      ordering medication to performing surgery, the stakes are high. Widespread
      adoption of Electronic Health Record (EHR) and Computerized Provider Order Entry
      (CPOE) systems makes patient selection using a computer screen a frequent task
      for clinicians. Careful design of the user interface can help mitigate the
      problem by helping providers recall their patients' identities, accurately select
      their names, and spot errors before orders are submitted. We propose a catalog of
      twenty seven distinct user interface techniques, organized according to a task
      analysis. An associated video demonstrates eighteen of those techniques. EHR
      designers who consider a wider range of human-computer interaction techniques
      could reduce selection errors, but verification of efficacy is still needed. 

PMID- 25954416
TI  - Concordance of Electronic Health Record (EHR) Data Describing Delirium at a VA
      Hospital.
AB  - BACKGROUND: Delirium is a common syndrome in elderly hospitalized patients that
      is correlated with poor outcomes and higher costs yet health care teams often
      overlook its diagnosis and treatment. Poor data quality in EHR systems can be
      contributing to this as a common tool teams use to communicate and record data
      about their patients. METHODS: Data were gathered from 30 patients chosen
      randomly that spanned various data domains in the EHR. These were analyzed for
      concordance as an indicator of data quality. RESULTS: Concordance was high
      between the physician and nursing narrative documentation. The other domains of
      data were drastically less concordant. DISCUSSION: The low concordance between
      structured and narrative data domains suggests that clinicians are forgoing the
      features available in modern EHR systems and opting to work in narrative. For
      informatics, this can be troubling as narrative data are difficult to compute.

PMID- 25954417
TI  - Pediatric readmission classification using stacked regularized logistic
      regression models.
AB  - BACKGROUND: Regulations and privacy concerns often hinder exchange of healthcare
      data between hospitals or other healthcare providers. Sharing predictive models
      built on original data and averaging their results offers an alternative to more
      efficient prediction of outcomes on new cases. Although one can choose from many
      techniques to combine outputs from different predictive models, it is difficult
      to find studies that try to interpret the results obtained from ensemble-learning
      methods. METHODS: We propose a novel approach to classification based on models
      from different hospitals that allows a high level of performance along with
      comprehensibility of obtained results. Our approach is based on regularized
      sparse regression models in two hierarchical levels and exploits the
      interpretability of obtained regression coefficients to rank the contribution of
      hospitals in terms of outcome prediction. RESULTS: The proposed approach was used
      to predict the 30-days all-cause readmissions for pediatric patients in 54
      Californian hospitals. Using repeated holdout evaluation, including more than
      60,000 hospital discharge records, we compared the proposed approach to
      alternative approaches. The performance of two-level classification model was
      measured using the Area Under the ROC Curve (AUC) with an additional evaluation
      that uncovered the importance and contribution of each single data source (i.e.
      hospital) to the final result. The results for the best distributed model
      (AUC=0.787, 95% CI: 0.780-0.794) demonstrate no significant difference in terms
      of AUC performance when compared to a single elastic net model built on all
      available data (AUC=0.789, 95% CI: 0.781-0.796). CONCLUSIONS: This paper presents
      a novel approach to improved classification with shared predictive models for
      environments where centralized collection of data is not possible. The
      significant improvements in classification performance and interpretability of
      results demonstrate the effectiveness of our approach.

PMID- 25954418
TI  - Text Classification towards Detecting Misdiagnosis of an Epilepsy Syndrome in a
      Pediatric Population.
AB  - When attempting to identify a specific epilepsy syndrome, physicians are often
      unable to make or agree upon a diagnosis. This is further complicated by the fact
      that the current classification and diagnosis of epilepsy requires specialized
      training and the use of resources not typically available to the average
      clinician, such as training to recognize specific seizure types and
      electroencephalography (EEG). Even when training and resources are available,
      expert epileptologists often find it challenging to identify seizure types and to
      distinguish between specific epilepsy syndromes. Information relevant to the
      diagnosis is present in narrative form in the medical record across several
      visits for an individual patient. Our ultimate goal is to create a system that
      will assist physicians in the diagnosis of epilepsy. This paper explores, as a
      baseline, text classification methods that attempt to correlate the narrative
      text features to the diagnosis of West syndrome (Infantile Spasms), using data
      from Phoenix Children's Hospital (PCH). We tested these methods against a dataset
      containing known (coded) diagnosis of West Syndrome, and found the best
      performing method to have a precision / recall / f-measure of 76.8 / 66.7 / 71.4
      when evaluated with 10-fold cross validation.

PMID- 25954419
TI  - Adding flexible temporal constraints to identify chronic comorbid conditions in
      ambulatory claims data.
AB  - Chronic comorbid conditions are important predictors of primary care outcomes,
      provide context for clinical decisions, and are potential complications of
      diseases and treatments. Comorbidity indices and multimorbidity categorization
      strategies based on administrative claims data enumerate diagnostic codes in
      easily modifiable lists, but usually have inflexible temporal requirements, such
      as requiring two claims greater than 30 days apart, or three claims in three
      quarters. Table structures and claims data search algorithms were developed to
      support flexible temporal constraints. Tables of disease categories allow
      subgroups with different numbers of events, different times between similar
      claims, variable periods of interest, and specified diagnostic code
      substitutability. The strategy was tested on five years of private insurance
      claims from 2.2 million working age adults. The contrast between rarely recorded,
      high prevalence diagnoses (smoking and obesity) and frequently recorded but not
      necessarily chronic diagnoses (musculoskeletal complaints) demonstrated the
      advantage of flexible temporal criteria. 

PMID- 25954420
TI  - Designing a clinical dashboard to fill information gaps in the emergency
      department.
AB  - Data fragmentation within electronic health records causes gaps in the
      information readily available to clinicians. We investigated the information
      needs of emergency medicine clinicians in order to design an electronic dashboard
      to fill information gaps in the emergency department. An online survey was
      distributed to all emergency medicine physicians at a large, urban academic
      medical center. The survey response rate was 48% (52/109). The clinical
      information items reported to be most helpful while caring for patients in the
      emergency department were vital signs, electrocardiogram (ECG) reports, previous
      discharge summaries, and previous lab results. Brief structured interviews were
      also conducted with 18 clinicians during their shifts in the emergency
      department. From the interviews, three themes emerged: 1) difficulty accessing
      vital signs, 2) difficulty accessing point-of-care tests, and 3) difficulty
      comparing the current ECG with the previous ECG. An emergency medicine clinical
      dashboard was developed to address these difficulties. 

PMID- 25954421
TI  - SOEMPI: A Secure Open Enterprise Master Patient Index Software Toolkit for
      Private Record Linkage.
AB  - To mitigate bias in multi-institutional research studies, healthcare
      organizations need to integrate patient records. However, this process must be
      accomplished without disclosing the identities of the corresponding patients.
      Various private record linkage (PRL) techniques have been proposed, but there is
      a lack of translation into practice because no software suite supports the entire
      PRL lifecycle. This paper addresses this issue with the introduction of the
      Secure Open Enterprise Master Patient Index (SOEMPI). We show how SOEMPI covers
      the PRL lifecycle, illustrate the implementation of several PRL protocols, and
      provide a runtime analysis for the integration of two datasets consisting of
      10,000 records. While the PRL process is slower than a non-secure setting, our
      analysis shows the majority of processes in a PRL protocol require several
      seconds or less and that SOEMPI completes the process in approximately two
      minutes, which is a practical amount of time for integration. 

PMID- 25954422
TI  - An Algorithm Using Twelve Properties of Antibiotics to Find the Recommended
      Antibiotics, as in CPGs.
AB  - BACKGROUND: Clinical Decision Support Systems (CDSS) incorporating
      justifications, updating and adjustable recommendations can considerably improve
      the quality of healthcare. We propose a new approach to the design of CDSS for
      empiric antibiotic prescription, based on implementation of the deeper medical
      reasoning used by experts in the development of clinical practice guidelines
      (CPGs), to deduce the recommended antibiotics. METHODS: We investigated two
      methods ("exclusion" versus "scoring") for reproducing this reasoning based on
      antibiotic properties. RESULTS: The "exclusion" method reproduced expert
      reasoning the more accurately, retrieving the full list of recommended
      antibiotics for almost all clinical situations. DISCUSSION: This approach has
      several advantages: (i) it provides convincing explanations for physicians; (ii)
      updating could easily be incorporated into the CDSS; (iii) it can provide
      recommendations for clinical situations missing from CPGs.

PMID- 25954423
TI  - Patient-centered appointment scheduling using agent-based simulation.
AB  - Enhanced access and continuity are key components of patient-centered care.
      Existing studies show that several interventions such as providing same day
      appointments, walk-in services, after-hours care, and group appointments, have
      been used to redesign the healthcare systems for improved access to primary care.
      However, an intervention focusing on a single component of care delivery (i.e.
      improving access to acute care) might have a negative impact other components of
      the system (i.e. reduced continuity of care for chronic patients). Therefore,
      primary care clinics should consider implementing multiple interventions tailored
      for their patient population needs. We collected rapid ethnography and
      observations to better understand clinic workflow and key constraints. We then
      developed an agent-based simulation model that includes all access modalities
      (appointments, walk-ins, and after-hours access), incorporate resources and key
      constraints and determine the best appointment scheduling method that improves
      access and continuity of care. This paper demonstrates the value of simulation
      models to test a variety of alternative strategies to improve access to care
      through scheduling. 

PMID- 25954424
TI  - Confidence and Information Access in Clinical Decision-Making: An Examination of
      the Cognitive Processes that affect the Information-seeking Behavior of
      Physicians.
AB  - Clinical decision-making involves the interplay between cognitive processes and
      physicians' perceptions of confidence in the context of their information-seeking
      behavior. The objectives of the study are: to examine how these concepts
      interact, to determine whether physician confidence, defined in relation to
      information need, affects clinical decision-making, and if information access
      improves decision accuracy. We analyzed previously collected data about resident
      physicians' perceptions of information need from a study comparing abstracts and
      full-text articles in clinical decision accuracy. We found that there is a
      significant relation between confidence and accuracy (phi=0.164, p<0.01). We also
      found various differences in the alignment of confidence and accuracy,
      demonstrating the concepts of underconfidence and overconfidence across years of
      clinical experience. Access to online literature also has a significant effect on
      accuracy (p<0.001). These results highlight possible CDSS strategies to reduce
      medical errors. 

PMID- 25954425
TI  - An integrated billing application to streamline clinician workflow.
AB  - Between 2008 and 2010, our academic medical center transitioned to electronic
      provider documentation using a commercial electronic health record system. For
      attending physicians, one of the most frustrating aspects of this experience was
      the system's failure to support their existing electronic billing workflow.
      Because of poor system integration, it was difficult to verify the supporting
      documentation for each bill and impractical to track whether billable notes had
      corresponding charges. We developed and deployed in 2011 an integrated billing
      application called "iCharge" that streamlines clinicians' documentation and
      billing workflow, and simultaneously populates the inpatient problem list using
      billing diagnosis codes. Each month, over 550 physicians use iCharge to submit
      approximately 23,000 professional service charges for over 4,200 patients. On
      average, about 2.5 new problems are added to each patient's problem list. This
      paper describes the challenges and benefits of workflow integration across
      disparate applications and presents an example of innovative software development
      within a commercial EHR framework. 

PMID- 25954426
TI  - Mining consumer health vocabulary from community-generated text.
AB  - Community-generated text corpora can be a valuable resource to extract consumer
      health vocabulary (CHV) and link them to professional terminologies and
      alternative variants. In this research, we propose a pattern-based text-mining
      approach to identify pairs of CHV and professional terms from Wikipedia, a large
      text corpus created and maintained by the community. A novel measure, leveraging
      the ratio of frequency of occurrence, was used to differentiate consumer terms
      from professional terms. We empirically evaluated the applicability of this
      approach using a large data sample consisting of MedLine abstracts and all posts
      from an online health forum, MedHelp. The results show that the proposed approach
      is able to identify synonymous pairs and label the terms as either consumer or
      professional term with high accuracy. We conclude that the proposed approach
      provides great potential to produce a high quality CHV to improve the performance
      of computational applications in processing consumer-generated health text. 

PMID- 25954427
TI  - Adverse Drug Event-based Stratification of Tumor Mutations: A Case Study of
      Breast Cancer Patients Receiving Aromatase Inhibitors.
AB  - Adverse drug events (ADEs) are a critical factor for selecting cancer therapy
      options. The underlying molecular mechanisms of ADEs associated with cancer
      therapy drugs may overlap with their antineoplastic mechanisms; an aspect of
      toxicity. In the present study, we develop a novel knowledge-driven approach that
      provides an ADE-based stratification (ADEStrata) of tumor mutations. We
      demonstrate clinical utility of the ADEStrata approach through performing a case
      study of breast invasive carcinoma (BRCA) patients receiving aromatase inhibitors
      (AI) from The Cancer Genome Atlas (TCGA) (n=212), focusing on the musculoskeletal
      adverse events (MS-AEs). We prioritized somatic variants in a manner that is
      guided by MS-AEs codified as 6 Human Phenotype Ontology (HPO) terms. Pathway
      enrichment and hierarchical clustering of prioritized variants reveals clusters
      associated with overall survival. We demonstrated that the prediction of per
      patient ADE propensity simultaneously identifies high-risk patients experiencing
      poor outcomes. In conclusion, the ADEStrata approach could produce clinically and
      biologically meaningful tumor subtypes that are potentially predictive of the
      drug response to the cancer therapy drugs. 

PMID- 25954429
TI  - Exploring joint disease risk prediction.
AB  - Disease risk prediction has been a central topic of medical informatics. Although
      various risk prediction models have been studied in the literature, the vast
      majority were designed to be single-task, i.e. they only consider one target
      disease at a time. This becomes a limitation when in practice we are dealing with
      two or more diseases that are related to each other in terms of sharing common
      comorbidities, symptoms, risk factors, etc., because single-task prediction
      models are not equipped to identify these associations across different tasks. In
      this paper we address this limitation by exploring the application of multi-task
      learning framework to joint disease risk prediction. Specifically, we
      characterize the disease relatedness by assuming that the risk predictors
      underlying these diseases have overlap. We develop an optimization-based
      formulation that can simultaneously predict the risk for all diseases and learn
      the shared predictors. Our model is applied to a real Electronic Health Record
      (EHR) database with 7,839 patients, among which 1,127 developed Congestive Heart
      Failure (CHF) and 477 developed Chronic Obstructive Pulmonary Disease (COPD). We
      demonstrate that a properly designed multi-task learning algorithm is viable for
      joint disease risk prediction and it can discover clinical insights that single
      task models would overlook. 

PMID- 25954428
TI  - Clinical risk prediction by exploring high-order feature correlations.
AB  - Clinical risk prediction is one important problem in medical informatics, and
      logistic regression is one of the most widely used approaches for clinical risk
      prediction. In many cases, the number of potential risk factors is fairly large
      and the actual set of factors that contribute to the risk is small. Therefore
      sparse logistic regression is proposed, which can not only predict the clinical
      risk but also identify the set of relevant risk factors. The inputs of logistic
      regression and sparse logistic regression are required to be in vector form. This
      limits the applicability of these models in the problems when the data cannot be
      naturally represented vectors (e.g., medical images are two-dimensional
      matrices). To handle the cases when the data are in the form of multi-dimensional
      arrays, we propose HOSLR: High-Order Sparse Logistic Regression, which can be
      viewed as a high order extension of sparse logistic regression. Instead of
      solving one classification vector as in conventional logistic regression, we
      solve for K classification vectors in HOSLR (K is the number of modes in the
      data). A block proximal descent approach is proposed to solve the problem and its
      convergence is guaranteed. Finally we validate the effectiveness of HOSLR on
      predicting the onset risk of patients with Alzheimer's disease and heart failure.

PMID- 25954430
TI  - Clinical decision support for whole genome sequence information leveraging a
      service-oriented architecture: a prototype.
AB  - Whole genome sequence (WGS) information could soon be routinely available to
      clinicians to support the personalized care of their patients. At such time,
      clinical decision support (CDS) integrated into the clinical workflow will likely
      be necessary to support genome-guided clinical care. Nevertheless, developing CDS
      capabilities for WGS information presents many unique challenges that need to be
      overcome for such approaches to be effective. In this manuscript, we describe the
      development of a prototype CDS system that is capable of providing genome-guided
      CDS at the point of care and within the clinical workflow. To demonstrate the
      functionality of this prototype, we implemented a clinical scenario of a
      hypothetical patient at high risk for Lynch Syndrome based on his genomic
      information. We demonstrate that this system can effectively use service-oriented
      architecture principles and standards-based components to deliver point of care
      CDS for WGS information in real-time. 

PMID- 25954431
TI  - Stochastic Gradient Descent and the Prediction of MeSH for PubMed Records.
AB  - Stochastic Gradient Descent (SGD) has gained popularity for solving large scale
      supervised machine learning problems. It provides a rapid method for minimizing a
      number of loss functions and is applicable to Support Vector Machine (SVM) and
      Logistic optimizations. However SGD does not provide a convenient stopping
      criterion. Generally an optimal number of iterations over the data may be
      determined using held out data. Here we compare stopping predictions based on
      held out data with simply stopping at a fixed number of iterations and show that
      the latter works as well as the former for a number of commonly studied text
      classification problems. In particular fixed stopping works well for MeSH((r))
      predictions on PubMed((r)) records. We also surveyed the published algorithms for
      SVM learning on large data sets, and chose three for comparison: PROBE, SVMperf,
      and Liblinear and compared them with SGD with a fixed number of iterations. We
      find SGD with a fixed number of iterations performs as well as these alternative
      methods and is much faster to compute. As an application we made SGD-SVM
      predictions for all MeSH terms and used the Pool Adjacent Violators (PAV)
      algorithm to convert these predictions to probabilities. Such probabilistic
      predictions lead to ranked MeSH term predictions superior to previously published
      results on two test sets. 

PMID- 25954432
TI  - Using String Metrics to Identify Patient Journeys through Care Pathways.
AB  - Given a computerized representation of a care pathway and an electronic record of
      a patient's clinical journey, with potential omissions, insertions,
      discontinuities and reordering, we show that we can accurately match the journey
      to a particular route through the pathway by converting the problem into a string
      matching one. We discover that normalized string metrics lead to more unique
      pathway matches than non-normalized string metrics and should therefore be given
      preference when using these techniques. 

PMID- 25954433
TI  - Desiderata for an authoritative Representation of MeSH in RDF.
AB  - The Semantic Web provides a framework for the integration of resources on the
      web, which facilitates information integration and interoperability. RDF is the
      main representation format for Linked Open Data (LOD). However, datasets are not
      always made available in RDF by their producers and the Semantic Web community
      has had to convert some of these datasets to RDF in order for these datasets to
      participate in the LOD cloud. As a result, the LOD cloud sometimes contains
      outdated, partial and even inaccurate RDF datasets. We review the LOD landscape
      for one of these resources, MeSH, and analyze the characteristics of six existing
      representations in order to identify desirable features for an authoritative
      version, for which we create a prototype. We illustrate the suitability of this
      prototype on three common use cases. NLM intends to release an authoritative
      representation of MeSH in RDF (beta version) in the Fall of 2014. 

PMID- 25954435
TI  - Information is in the eye of the beholder: Seeking information on the MMR vaccine
      through an Internet search engine.
AB  - Vaccination campaigns are one of the most important and successful public health
      programs ever undertaken. People who want to learn about vaccines in order to
      make an informed decision on whether to vaccinate are faced with a wealth of
      information on the Internet, both for and against vaccinations. In this paper we
      develop an automated way to score Internet search queries and web pages as to the
      likelihood that a person making these queries or reading those pages would decide
      to vaccinate. We apply this method to data from a major Internet search engine,
      while people seek information about the Measles, Mumps and Rubella (MMR) vaccine.
      We show that our method is accurate, and use it to learn about the information
      acquisition process of people. Our results show that people who are pro
      vaccination as well as people who are anti-vaccination seek similar information,
      but browsing this information has differing effect on their future browsing.
      These findings demonstrate the need for health authorities to tailor their
      information according to the current stance of users. 

PMID- 25954434
TI  - Comparing the value of mammographic features and genetic variants in breast
      cancer risk prediction.
AB  - The goal of this study was to compare the value of mammographic features and
      genetic variants for breast cancer risk prediction with Bayesian reasoning and
      information theory. We conducted a retrospective case-control study, collecting
      mammographic findings and high-frequency/low-penetrance genetic variants from an
      existing personalized medicine data repository. We trained and tested Bayesian
      networks for mammographic findings and genetic variants respectively. We found
      that mammographic findings had a higher discriminative ability than genetic
      variants for improving breast cancer risk prediction in terms of the area under
      the ROC curve. We compared the value of each mammographic feature and genetic
      variant for breast risk prediction in terms of mutual information, with and
      without consideration of interactions of those risk factors. We also identified
      the interactions between mammographic features and genetic variants in an attempt
      to prioritize mammographic features and genetic variants to efficiently predict
      the risk of breast cancer. 

PMID- 25954436
TI  - MEDCIS: Multi-Modality Epilepsy Data Capture and Integration System.
AB  - Sudden Unexpected Death in Epilepsy (SUDEP) is the leading mode of epilepsy
      related death and is most common in patients with intractable, frequent, and
      continuing seizures. A statistically significant cohort of patients for SUDEP
      study requires meticulous, prospective follow up of a large population that is at
      an elevated risk, best represented by the Epilepsy Monitoring Unit (EMU) patient
      population. Multiple EMUs need to collaborate, share data for building a larger
      cohort of potential SUDEP patient using a state-of-the-art informatics
      infrastructure. To address the challenges of data integration and data access
      from multiple EMUs, we developed the Multi-Modality Epilepsy Data Capture and
      Integration System (MEDCIS) that combines retrospective clinical free text
      processing using NLP, prospective structured data capture using an ontology
      driven interface, interfaces for cohort search and signal visualization, all in a
      single integrated environment. A dedicated Epilepsy and Seizure Ontology (EpSO)
      has been used to streamline the user interfaces, enhance its usability, and
      enable mappings across distributed databases so that federated queries can be
      executed. MEDCIS contained 936 patient data sets from the EMUs of University
      Hospitals Case Medical Center (UH CMC) in Cleveland and Northwestern Memorial
      Hospital (NMH) in Chicago. Patients from UH CMC and NMH were stored in different
      databases and then federated through MEDCIS using EpSO and our mapping module.
      More than 77GB of multi-modal signal data were processed using the Cloudwave
      pipeline and made available for rendering through the web-interface. About 74% of
      the 40 open clinical questions of interest were answerable accurately using the
      EpSO-driven VISual AGregagator and Explorer (VISAGE) interface. Questions not
      directly answerable were either due to their inherent computational complexity,
      the unavailability of primary information, or the scope of concept that has been
      formulated in the existing EpSO terminology system. 

PMID- 25954437
TI  - Towards drug repositioning: a unified computational framework for integrating
      multiple aspects of drug similarity and disease similarity.
AB  - In response to the high cost and high risk associated with traditional de novo
      drug discovery, investigation of potential additional uses for existing drugs,
      also known as drug repositioning, has attracted increasing attention from both
      the pharmaceutical industry and the research community. In this paper, we propose
      a unified computational framework, called DDR, to predict novel drug-disease
      associations. DDR formulates the task of hypothesis generation for drug
      repositioning as a constrained nonlinear optimization problem. It utilizes
      multiple drug similarity networks, multiple disease similarity networks, and
      known drug-disease associations to explore potential new associations among drugs
      and diseases with no known links. A large-scale study was conducted using 799
      drugs against 719 diseases. Experimental results demonstrated the effectiveness
      of the approach. In addition, DDR ranked drug and disease information sources
      based on their contributions to the prediction, thus paving the way for
      prioritizing multiple data sources and building more reliable drug repositioning
      models. Particularly, some of our novel predictions of drug-disease associations
      were supported by clinical trials databases, showing that DDR could serve as a
      useful tool in drug discovery to efficiently identify potential novel uses for
      existing drugs. 

PMID- 25954438
TI  - Using language models to identify relevant new information in inpatient clinical
      notes.
AB  - Redundant information in clinical notes within electronic health record (EHR)
      systems is ubiquitous and may negatively impact the use of these notes by
      clinicians, and, potentially, the efficiency of patient care delivery. Automated
      methods to identify redundant versus relevant new information may provide a
      valuable tool for clinicians to better synthesize patient information and
      navigate to clinically important details. In this study, we investigated the use
      of language models for identification of new information in inpatient notes, and
      evaluated our methods using expert-derived reference standards. The best method
      achieved precision of 0.743, recall of 0.832 and F1-measure of 0.784. The average
      proportion of redundant information was similar between inpatient and outpatient
      progress notes (76.6% (SD=17.3%) and 76.7% (SD=14.0%), respectively). Advanced
      practice providers tended to have higher rates of redundancy in their notes
      compared to physicians. Future investigation includes the addition of semantic
      components and visualization of new information. 

PMID- 25954439
TI  - Developing Analytical Inspection Criteria for Health IT Personnel with Minimum
      Training in Cognitive Ergonomics: A Practical Solution to EHR Improving EHR
      Usability.
AB  - EHR usability has been identified as a major barrier to care quality
      optimization. One major challenge of improving EHR usability is the lack of
      systematic training in usability or cognitive ergonomics for EHR
      designers/developers in the vendor community and EHR analysts making significant
      configurations in healthcare organizations. A practical solution is to provide
      usability inspection tools that can be easily operationalized by EHR analysts.
      This project is aimed at developing a set of usability tools with demonstrated
      validity and reliability. We present a preliminary study of a metric for
      cognitive transparency and an exploratory experiment testing its validity in
      predicting the effectiveness of action-effect mapping. Despite the pilot nature
      of both, we found high sensitivity and specificity of the metric and higher
      response accuracy within a shorter time for users to determine action-effect
      mappings in transparent user interface controls. We plan to expand the sample
      size in our empirical study. 

PMID- 25954440
TI  - Automatically Detecting Acute Myocardial Infarction Events from EHR Text: A
      Preliminary Study.
AB  - The Worcester Heart Attack Study (WHAS) is a population-based surveillance
      project examining trends in the incidence, in-hospital, and long-term survival
      rates of acute myocardial infarction (AMI) among residents of central
      Massachusetts. It provides insights into various aspects of AMI. Much of the data
      has been assessed manually. We are developing supervised machine learning
      approaches to automate this process. Since the existing WHAS data cannot be used
      directly for an automated system, we first annotated the AMI information in
      electronic health records (EHR). With strict inter-annotator agreement over 0.74
      and un-strict agreement over 0.9 of Cohen's kappa, we annotated 105 EHR discharge
      summaries (135k tokens). Subsequently, we applied the state-of-the-art supervised
      machine-learning model, Conditional Random Fields (CRFs) for AMI detection. We
      explored different approaches to overcome the data sparseness challenge and our
      results showed that cluster-based word features achieved the highest performance.

PMID- 25954441
TI  - A Comparison of Data Driven-based Measures of Adherence to Oral Hypoglycemic
      Agents in Medicaid Patients.
AB  - We evaluated and compared different methods for measuring adherence to Oral
      Antihyperglycemic Agents (OHA), based on the correlation between these measures
      and glycated hemoglobin A1C (HbA1c) levels in Medicaid patients with Type 2
      diabetes. An observational sample of 831 Medicaid patients with Type 2 diabetes
      who had HbA1c test results recorded between January 1, 2001 and December 31, 2005
      was identified in the Indiana Network of Patient Care (INPC). OHA adherence was
      measured by medication possession ratio (MPR), proportion of days covered (PDC),
      and the number of gaps (GAP) for 3, 6, and 12-month intervals prior to the HbA1c
      test date. All three OHA adherence measurements showed consistent and significant
      correlation with HbA1c level. The 6-month PDC showed the strongest association
      with HbA1c levels in both unadjusted (-1.07, P<0.0001) and adjusted (-1.12,
      P<0.0001) models. 

PMID- 25954442
TI  - Sharing my health data: a survey of data sharing preferences of healthy
      individuals.
AB  - We interviewed 70 healthy volunteers to understand their choices about how the
      information in their health record should be shared for research. Twenty-eight
      survey questions captured individual preferences of healthy volunteers. The
      results showed that respondents felt comfortable participating in research if
      they were given choices about which portions of their medical data would be
      shared, and with whom those data would be shared. Respondents indicated a strong
      preference towards controlling access to specific data (83%), and a large
      proportion (68%) indicated concern about the possibility of their data being used
      by for-profit entities. The results suggest that transparency in the process of
      sharing is an important factor in the decision to share clinical data for
      research. 

PMID- 25954443
TI  - Automated extraction of family history information from clinical notes.
AB  - Despite increased functionality for obtaining family history in a structured
      format within electronic health record systems, clinical notes often still
      contain this information. We developed and evaluated an Unstructured Information
      Management Application (UIMA)-based natural language processing (NLP) module for
      automated extraction of family history information with functionality for
      identifying statements, observations (e.g., disease or procedure), relative or
      side of family with attributes (i.e., vital status, age of diagnosis, certainty,
      and negation), and predication ("indicator phrases"), the latter of which was
      used to establish relationships between observations and family member. The
      family history NLP system demonstrated F-scores of 66.9, 92.4, 82.9, 57.3, 97.7,
      and 61.9 for detection of family history statements, family member
      identification, observation identification, negation identification, vital
      status, and overall extraction of the predications between family members and
      observations, respectively. While the system performed well for detection of
      family history statements and predication constituents, further work is needed to
      improve extraction of certainty and temporal modifications. 

PMID- 25954444
TI  - The EHR's roles in collaboration between providers: A qualitative study.
AB  - OBJECTIVE: Examine how the Electronic Health Record (EHR) and its related systems
      support or inhibit provider collaboration. BACKGROUND: Health care systems in the
      US are simultaneously implementing EHRs and transitioning to more collaborative
      delivery systems; this study examines the interaction between these two changes.
      METHODS: This qualitative study of five US EHR implementations included 49
      interviews and over 60 hours of provider observation. We examined the role of the
      EHR in building relationships, communicating, coordinating, and collaborative
      decision-making. RESULTS: The EHR plays four roles in collaboration: a
      repository, a messenger, an orchestrator, and a monitor. While EHR performance
      varied, common themes were decreased trust due to poor quality documentation,
      incomplete communication, potential for increased effectiveness through better
      coordination, and the emerging role of the EHR in identifying performance gaps.
      CONCLUSION: Both organizational and technical innovations are needed if the EHR
      is to truly support collaborative behaviors.

PMID- 25954445
TI  - MedMinify: An Advice-giving System for Simplifying the Schedules of Daily Home
      Medication Regimens Used to Treat Chronic Conditions.
AB  - For those with high blood pressure, diabetes, or high cholesterol, adherence to a
      home medication regimen is important for health. Reductions in the number of
      daily medication-taking events or daily pill burden improve adherence. A novel
      advice-giving computer application was developed using the SMART platform to
      generate advice on how to potentially simplify home medication regimens.
      MedMinify generated advice for 41.3% of 1,500 home medication regimens for adults
      age 60 years and older with chronic medical conditions. If the advice given by
      MedMinify were implemented, 320 regimen changes would have reduced daily
      medication-taking events while an additional 295 changes would have decreased the
      daily pill burden. The application identified four serious drug-drug interactions
      and so advised against taking two pairs of medications simultaneously. MedMinify
      can give advice to change home medication regimens that could result in simpler
      home medication-taking schedules. 

PMID- 25954446
TI  - Could Patient Self-reported Health Data Complement EHR for Phenotyping?
AB  - Electronic health records (EHRs) have been used as a valuable data source for
      phenotyping. However, this method suffers from inherent data quality issues like
      data missingness. As patient self-reported health data are increasingly
      available, it is useful to know how the two data sources compare with each other
      for phenotyping. This study addresses this research question. We used self
      reported diabetes status for 2,249 patients treated at Columbia University
      Medical Center and the well-known eMERGE EHR phenotyping algorithm for Type 2
      diabetes mellitus (DM2) to conduct the experiment. The eMERGE algorithm achieved
      high specificity (.97) but low sensitivity (.32) among this patient cohort. About
      87% of the patients with self-reported diabetes had at least one ICD-9 code, one
      medication, or one lab result supporting a DM2 diagnosis, implying the remaining
      13% may have missing or incorrect self-reports. We discuss the tradeoffs in both
      data sources and in combining them for phenotyping. 

PMID- 25954447
TI  - Risk prediction for acute hypotensive patients by using gap constrained
      sequential contrast patterns.
AB  - The development of acute hypotension in a critical care patient causes decreased
      tissue perfusion, which can lead to multiple organ failures. Existing systems
      that employ population level prognostic scores to stratify the risks of critical
      care patients based on hypotensive episodes are suboptimal in predicting
      impending critical conditions, or in directing an effective goal-oriented
      therapy. In this work, we propose a sequential pattern mining approach which
      target novel and informative sequential contrast patterns for the detection of
      hypotension episodes. Our results demonstrate the competitiveness of the
      approach, in terms of both prediction performance as well as knowledge
      interpretability. Hence, sequential patterns-based computational biomarkers can
      help comprehend unusual episodes in critical care patients ahead of time for
      early warning systems. Sequential patterns can thus aid in the development of a
      powerful critical care knowledge discovery framework for facilitating novel
      patient treatment plans. 

PMID- 25954448
TI  - A novel method to assess incompleteness of mammography reports.
AB  - Mammography has been shown to improve outcomes of women with breast cancer, but
      it is subject to inter-reader variability. One well-documented source of such
      variability is in the content of mammography reports. The mammography report is
      of crucial importance, since it documents the radiologist's imaging observations,
      interpretation of those observations in terms of likelihood of malignancy, and
      suggested patient management. In this paper, we define an incompleteness score to
      measure how incomplete the information content is in the mammography report and
      provide an algorithm to calculate this metric. We then show that the
      incompleteness score can be used to predict errors in interpretation. This method
      has 82.6% accuracy at predicting errors in interpretation and can possibly reduce
      total diagnostic errors by up to 21.7%. Such a method can easily be modified to
      suit other domains that depend on quality reporting. 

PMID- 25954449
TI  - How do interruptions impact nurses' visual scanning patterns when using barcode
      medication administration systems?
AB  - While barcode medication administration (BCMA) systems have the potential to
      reduce medication errors, they may introduce errors, side effects, and hazards
      into the medication administration process. Studies of BCMA systems should
      therefore consider the interrelated nature of health information technology (IT)
      use and sociotechnical systems. We aimed to understand how the introduction of
      interruptions into the BCMA process impacts nurses' visual scanning patterns, a
      proxy for one component of cognitive processing. We used an eye tracker to record
      nurses' visual scanning patterns while administering a medication using BCMA.
      Nurses either performed the BCMA process in a controlled setting with no
      interruptions (n=25) or in a real clinical setting with interruptions (n=21). By
      comparing the visual scanning patterns between the two groups, we found that
      nurses in the interruptive environment identified less task-related information
      in a given period of time, and engaged in more information searching than
      information processing. 

PMID- 25954450
TI  - A method for analyzing commonalities in clinical trial target populations.
AB  - ClinicalTrials.gov presents great opportunities for analyzing commonalities in
      clinical trial target populations to facilitate knowledge reuse when designing
      eligibility criteria of future trials or to reveal potential systematic biases in
      selecting population subgroups for clinical research. Towards this goal, this
      paper presents a novel data resource for enabling such analyses. Our method
      includes two parts: (1) parsing and indexing eligibility criteria text; and (2)
      mining common eligibility features and attributes of common numeric features
      (e.g., A1c). We designed and built a database called "Commonalities in Target
      Populations of Clinical Trials" (COMPACT), which stores structured eligibility
      criteria and trial metadata in a readily computable format. We illustrate its use
      in an example analytic module called CONECT using COMPACT as the backend. Type 2
      diabetes is used as an example to analyze commonalities in the target populations
      of 4,493 clinical trials on this disease. 

PMID- 25954451
TI  - Predicting discharge mortality after acute ischemic stroke using balanced data.
AB  - Several models have been developed to predict stroke outcomes (e.g., stroke
      mortality, patient dependence, etc.) in recent decades. However, there is little
      discussion regarding the problem of between-class imbalance in stroke datasets,
      which leads to prediction bias and decreased performance. In this paper, we
      demonstrate the use of the Synthetic Minority Over-sampling Technique to overcome
      such problems. We also compare state of the art machine learning methods and
      construct a six-variable support vector machine (SVM) model to predict stroke
      mortality at discharge. Finally, we discuss how the identification of a reduced
      feature set allowed us to identify additional cases in our research database for
      validation testing. Our classifier achieved a c-statistic of 0.865 on the cross
      validated dataset, demonstrating good classification performance using a reduced
      set of variables. 

PMID- 25954452
TI  - A Service Oriented Architecture Approach to Achieve Interoperability between
      Immunization Information Systems in Iran.
AB  - Clinical decision support (CDS) systems can support vaccine forecasting and
      immunization reminders; however, immunization decision-making requires data from
      fragmented, independent systems. Interoperability and accurate data exchange
      between immunization information systems (IIS) is an essential factor to utilize
      Immunization CDS systems. Service oriented architecture (SOA) and Health Level 7
      (HL7) are dominant standards for web-based exchange of clinical information. We
      implemented a system based on SOA and HL7 v3 to support immunization CDS in Iran.
      We evaluated system performance by exchanging 1500 immunization records for
      roughly 400 infants between two IISs. System turnaround time is less than a
      minute for synchronous operation calls and the retrieved immunization history of
      infants were always identical in different systems. CDS generated reports were
      accordant to immunization guidelines and the calculations for next visit times
      were accurate. Interoperability is rare or nonexistent between IIS. Since inter
      state data exchange is rare in United States, this approach could be a good
      prototype to achieve interoperability of immunization information. 

PMID- 25954453
TI  - Syndromic surveillance in an ICD-10 world.
AB  - The Centers for Disease Control and Prevention's BioSense program is an
      integrated national public health surveillance system that uses electronic
      medical record (EMR) data to provide situational awareness for all-hazard health
      related events. Because the system leverages International Classification of
      Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) coded data from EMRs
      for syndromic surveillance, the upcoming Health and Human Services-mandated
      transition from ICD-9-CM to ICD-10-CM will have a significant impact. To
      translate across the two encoding systems, we developed a Mapping Reference Table
      (MRT) for the ICD-9/10 transition. We extracted ICD-9-CM codes binned to
      predefined syndromes and mapped each to its corresponding ICD-10-CM code(s).
      Then, we translated the output ICD-10-CM codes back to ICD-9-CM through a reverse
      translation validation process. Throughout the translation process, we examined
      outputs manually and incorporated annotated results into the MRT. The resulting
      MRT can be used to refine and update each existing syndromic surveillance
      definition in BioSense to be compatible with ICD-10-CM and consistently classify
      or bin any given emergency department visit into the correct syndrome regardless
      of coding system. 

PMID- 25954454
TI  - Divisive Hierarchical Clustering towards Identifying Clinically Significant Pre
      Diabetes Subpopulations.
AB  - Type 2 Diabetes Mellitus is a progressive disease with increased risk of
      developing serious complications. Identifying subpopulations and their relevant
      risk factors can contribute to the prevention and effective management of
      diabetes. We use a novel divisive hierarchical clustering technique to identify
      clinically interesting subpopulations in a large cohort of Olmsted County, MN
      residents. Our results show that our clustering algorithm successfully identified
      clinically interesting clusters consisting of patients with higher or lower risk
      of diabetes than the general population. The proposed algorithm offers fine
      control over the granularity of the clustering, has the ability to seamlessly
      discover and incorporate interactions among the risk factors, and can handle non
      proportional hazards, as well. It has the potential to significantly impact
      clinical practice by recognizing patients with specific risk factors who may
      benefit from an alternative management approach potentially leading to the
      prevention of diabetes and its complications. 

PMID- 25954455
TI  - Extracting patient demographics and personal medical information from online
      health forums.
AB  - Natural language processing has been successfully leveraged to extract patient
      information from unstructured clinical text. However the majority of the existing
      work targets at obtaining a specific category of clinical information through
      individual efforts. In the midst of the Health 2.0 wave, online health forums
      increasingly host abundant and diverse health-related information regarding the
      demographics and medical information of patients who are either actively
      participating in or passively reported at these forums. The potential categories
      of such information span a wide spectrum, whose extraction requires a systematic
      and comprehensive approach beyond the traditional isolated efforts that
      specialize in harvesting information of single categories. In this paper, we
      develop a new integrated biomedical NLP pipeline that automatically extracts a
      comprehensive set of patient demographics and medical information from online
      health forums. The pipeline can be adopted to construct structured personal
      health profiles from unstructured user-contributed content on eHealth social
      media sites. This paper describes key aspects of the pipeline as well as reports
      experimental results that show the system's satisfactory performance in
      accomplishing a series of NLP tasks of extracting patient information from online
      health forums. 

PMID- 25954456
TI  - Data model for personalized patient health guidelines: an exploratory study.
AB  - Practitioner guidelines simultaneously provide broad overviews and in-depth
      details of disease. Written for experts, they are difficult for patients to
      understand, yet patients often use these guidelines as a source of information to
      help them to learn about their health. Using practitioner guidelines along with
      patient information needs and preferences, we created a method to design an
      information model for providing patients access to their personal health
      information, linked to individualized, relevant supporting information from
      guidelines within a patient portal. This model consists of twelve classes of
      concepts. We manually reviewed and annotated medical records to demonstrate the
      validity of our model. Each class of the model was found within at least one
      patient's record, and seven classes of concepts appeared in over half of the
      patients' records annotated. These annotations show that the model produced by
      the method can be used to determine what guideline information is relevant to an
      individual patient, based on concepts in their health information. 

PMID- 25954457
TI  - Identification and management of information problems by emergency department
      staff.
AB  - Patient-care teams frequently encounter information problems during their daily
      activities. These information problems include wrong, outdated, conflicting,
      incomplete, or missing information. Information problems can negatively impact
      the patient-care workflow, lead to misunderstandings about patient information,
      and potentially lead to medical errors. Existing research focuses on
      understanding the cause of these information problems and the impact that they
      can have on the hospital's workflow. However, there is limited research on how
      patient-care teams currently identify and manage information problems that they
      encounter during their work. Through qualitative observations and interviews in
      an emergency department (ED), we identified the types of information problems
      encountered by ED staff, and examined how they identified and managed the
      information problems. We also discuss the impact that these information problems
      can have on the patient-care teams, including the cascading effects of
      information problems on workflow and the ambiguous accountability for fixing
      information problems within collaborative teams. 

PMID- 25954458
TI  - An Evaluation of Two Methods for Generating Synthetic HL7 Segments Reflecting
      Real-World Health Information Exchange Transactions.
AB  - Motivated by the need for readily available data for testing an open-source
      health information exchange platform, we developed and evaluated two methods for
      generating synthetic messages. The methods used HL7 version 2 messages obtained
      from the Indiana Network for Patient Care. Data from both methods were analyzed
      to assess how effectively the output reflected original 'real-world' data. The
      Markov Chain method (MCM) used an algorithm based on transitional probability
      matrix while the Music Box model (MBM) randomly selected messages of particular
      trigger type from the original data to generate new messages. The MBM was faster,
      generated shorter messages and exhibited less variation in message length. The
      MCM required more computational power, generated longer messages with more
      message length variability. Both methods exhibited adequate coverage, producing a
      high proportion of messages consistent with original messages. Both methods
      yielded similar rates of valid messages. 

PMID- 25954459
TI  - Scalable and High-Throughput Execution of Clinical Quality Measures from
      Electronic Health Records using MapReduce and the JBoss(r) Drools Engine.
AB  - Automated execution of electronic Clinical Quality Measures (eCQMs) from
      electronic health records (EHRs) on large patient populations remains a
      significant challenge, and the testability, interoperability, and scalability of
      measure execution are critical. The High Throughput Phenotyping (HTP;
      http://phenotypeportal.org) project aligns with these goals by using the
      standards-based HL7 Health Quality Measures Format (HQMF) and Quality Data Model
      (QDM) for measure specification, as well as Common Terminology Services 2 (CTS2)
      for semantic interpretation. The HQMF/QDM representation is automatically
      transformed into a JBoss((r)) Drools workflow, enabling horizontal scalability
      via clustering and MapReduce algorithms. Using Project Cypress, automated
      verification metrics can then be produced. Our results show linear scalability
      for nine executed 2014 Center for Medicare and Medicaid Services (CMS) eCQMs for
      eligible professionals and hospitals for >1,000,000 patients, and verified
      execution correctness of 96.4% based on Project Cypress test data of 58 eCQMs. 

PMID- 25954460
TI  - Knowledge crystallization and clinical priorities: evaluating how physicians
      collect and synthesize patient-related data.
AB  - Information seeking and synthesis are time consuming processes for physicians.
      Although systems have the potential to simplify these tasks, future improvements
      must be based on an understanding of how physicians perform these tasks during
      clinical prioritization. We enrolled 23 physicians in semi-structured focus
      groups discussing simulated inpatient populations. Participants documented and
      discussed their data gathering and prioritization processes. Transcripts were
      coded to identify themes and generalized process flows. Results indicate that
      data are collected to categorize and prioritize patients according to expected
      clinical course. When data do not support these expectations, or when
      categorization indicates potential for morbidity, physicians increase efforts to
      act or recategorize patients. Unexpected clinical changes have a significant
      impact on the decision-making and prioritization by clinicians. A modified
      version of the Knowledge Crystallization Framework helps to frame this work
      laying a foundation to advance information displays and facilitate information
      processing by physicians in clinical care environments. 

PMID- 25954462
TI  - Improving Clinical Data Integrity by using Data Adjudication Techniques for Data
      Received through a Health Information Exchange (HIE).
AB  - Growing participation in Healthcare Information Exchange (HIE) has created
      opportunities for the seamless integration of external data into an
      organization's own EHR and clinical workflows. The process of integrating
      external data has the potential to detect data integrity issues. Lack of
      critiquing external data before its incorporation can lead to data unfit for use
      in the clinical setting. HIE data adjudication, by detecting inconsistencies,
      physiological and temporal incompatibilities, data completeness and timeliness
      issues in HIE data, facilitates corrective actions and improves clinical data
      integrity. 

PMID- 25954461
TI  - Providing hospital patients with access to their medical records.
AB  - Being a hospital patient can be isolating and anxiety-inducing. We conducted two
      experiments to better understand clinician and patient perceptions about giving
      patients access to their medical records during hospital encounters. The first
      experiment, a survey of physicians, nurses, and other care providers (N=53),
      showed that most respondents were comfortable with the idea of providing patients
      with their clinical information. Some expressed reservations that patients might
      misunderstand information and become unnecessarily alarmed or offended. In the
      second experiment, we provided eight hospital patients with a daily copy of their
      full medical record-including physician notes and diagnostic test results. From
      semi-structured interviews with seven of these patients, we found that they
      perceived the information as highly useful even if they did not fully understand
      complex medical terms. Our results suggest that increased patient information
      sharing in the inpatient setting is beneficial and desirable to patients, and
      generally acceptable to clinicians. 

PMID- 25954464
TI  - Developing a formal representation for medication appropriateness criteria.
AB  - Inappropriate medications use (IMU) is a serious issue of global concern that
      leads to a waste of resources and potentially harms the patients. IMU can usually
      be identified by extracting information about the patient's conditions and
      treatments, and comparing them with "medication appropriateness criteria". To
      enable automation of these criteria, we developed a formal representation for
      them, which we called Objective Medication Appropriateness Criteria (OMAC). OMAC
      represents four aspects of the criteria: trigger, rules, action and metadata. Our
      evaluation showed that OMAC can completely represent explicitly defined
      medication appropriateness criteria using links to external knowledge sources.
      OMAC is the first formal representation for medication appropriateness criteria,
      and will enable development of structured rules for appropriate use of
      medications that can be implemented using standards for clinical decision
      support. 

PMID- 25954463
TI  - Development and Evaluation of Reference Standards for Image-based Telemedicine
      Diagnosis and Clinical Research Studies in Ophthalmology.
AB  - Information systems managing image-based data for telemedicine or clinical
      research applications require a reference standard representing the correct
      diagnosis. Accurate reference standards are difficult to establish because of
      imperfect agreement among physicians, and discrepancies between clinical vs.
      image-based diagnosis. This study is designed to describe the development and
      evaluation of reference standards for image-based diagnosis, which combine
      diagnostic impressions of multiple image readers with the actual clinical
      diagnoses. We show that agreement between image reading and clinical examinations
      was imperfect (689 [32%] discrepancies in 2148 image readings), as was inter
      reader agreement (kappa 0.490-0.652). This was improved by establishing an image
      based reference standard defined as the majority diagnosis given by three readers
      (13% discrepancies with image readers). It was further improved by establishing
      an overall reference standard that incorporated the clinical diagnosis (10%
      discrepancies with image readers). These principles of establishing reference
      standards may be applied to improve robustness of real-world systems supporting
      image-based diagnosis. 

PMID- 25954465
TI  - Design Considerations for Post-Acute Care mHealth: Patient Perspectives.
AB  - Many current mobile health applications ("apps") and most previous research have
      been directed at management of chronic illnesses. However, little is known about
      patient preferences and design considerations for apps intended to help in a post
      acute setting. Our team is developing an mHealth platform to engage patients in
      wound tracking to identify and manage surgical site infections (SSI) after
      hospital discharge. Post-discharge SSIs are a major source of morbidity and
      expense, and occur at a critical care transition when patients are physically and
      emotionally stressed. Through interviews with surgical patients who experienced
      SSI, we derived design considerations for such a post-acute care app. Key design
      qualities include: meeting basic accessibility, usability and security needs;
      encouraging patient-centeredness; facilitating better, more predictable
      communication; and supporting personalized management by providers. We illustrate
      our application of these guiding design considerations and propose a new
      framework for mHealth design based on illness duration and intensity. 

PMID- 25954466
TI  - Motivating the additional use of external validity: examining transportability in
      a model of glioblastoma multiforme.
AB  - Despite the growing ubiquity of data in the medical domain, it remains difficult
      to apply results from experimental and observational studies to additional
      populations suffering from the same disease. Many methods are employed for
      testing internal validity; yet limited effort is made in testing
      generalizability, or external validity. The development of disease models often
      suffers from this lack of validity testing and trained models frequently have
      worse performance on different populations, rendering them ineffective. In this
      work, we discuss the use of transportability theory, a causal graphical model
      examination, as a mechanism for determining what elements of a data resource can
      be shared or moved between a source and target population. A simplified Bayesian
      model of glioblastoma multiforme serves as the example for discussion and
      preliminary analysis. Examination over data collection hospitals from the TCGA
      dataset demonstrated improvement of prediction in a transported model over a
      baseline model. 

PMID- 25954467
TI  - Machine learning for risk prediction of acute coronary syndrome.
AB  - Acute coronary syndrome (ACS) accounts for 1.36 million hospitalizations and
      billions of dollars in costs in the United States alone. A major challenge to
      diagnosing and treating patients with suspected ACS is the significant symptom
      overlap between patients with and without ACS. There is a high cost to over- and
      under-treatment. Guidelines recommend early risk stratification of patients, but
      many tools lack sufficient accuracy for use in clinical practice. Prognostic
      indices often misrepresent clinical populations and rely on curated data. We used
      random forest and elastic net on 20,078 deidentified records with significant
      missing and noisy values to develop models that outperform existing ACS risk
      prediction tools. We found that the random forest (AUC = 0.848) significantly
      outperformed elastic net (AUC=0.818), ridge regression (AUC = 0.810), and the
      TIMI (AUC = 0.745) and GRACE (AUC = 0.623) scores. Our findings show that random
      forest applied to noisy and sparse data can perform on par with previously
      developed scoring metrics. 

PMID- 25954468
TI  - Enabling claims-based decision support through non-interruptive capture of
      admission diagnoses and provider billing codes.
AB  - The patient problem list, like administrative claims data, has become an
      important source of data for decision support, patient cohort identification, and
      alerting systems. A two-fold intervention to increase capture of problems on the
      problem list automatically - with minimal disruption to admitting and provider
      billing workflows - is described. For new patients with no prior data in the
      electronic health record, the intervention resulted in a statistically
      significant increase in the number of problems recorded to the problem list (3.8
      vs 2.9 problems post-and pre-intervention respectively, p value 2*10(-16)). The
      majority of problems were recorded in the first 24 hours of admission. The
      proportion of patients with at least one problem coded to the problem list within
      the first 24 hours increased from 94% to 98% before and after intervention (chi
      square 344, p value 2*10(-16)). ICD9 "V codes" connoting circumstances beyond
      disease were captured at a higher rate post intervention than before.
      Deyo/Charlson comorbidities derived from problem list data were more similar to
      those derived from claims data after the intervention than before (Jaccard
      similarity 0.3 post- vs 0.21 pre-intervention, p value 2*10(-16)). A workflow
      sensitive, non-interruptive means of capturing provider-entered codes early in
      admission can improve both the quantity and content of problems on the patient
      problem list. 

PMID- 25954469
TI  - A mobile/web app for long distance caregivers of older adults: functional
      requirements and design implications from a user centered design process.
AB  - Recent trends of population aging and globalization have required an increasing
      number of individuals to act as long distance caregivers (LDCs) to aging family
      members. Information technology solutions may ease the burden placed on LDCs by
      providing remote monitoring, easier access to information and enhanced
      communication. While some technology tools have been introduced, the information
      and technology needs of LDCs in particular are not well understood. Consequently,
      a needs assessment was performed by using video conferencing software to conduct
      semi-structured interviews with 10 LDCs. Interviews were enriched through the use
      of stimulus materials that included the demonstration of a prototype LDC health
      management web/mobile app. Responses were recorded, transcribed and then
      analyzed. Subjects indicated that information regarding medication regimens and
      adherence, calendaring, and cognitive health were most needed. Participants also
      described needs for video calling, activity data regarding sleep and physical
      exercise, asynchronous communication, photo sharing, journaling, access to online
      health resources, real-time monitoring, an overall summary of health, and
      feedback/suggestions to help them improve as caregivers. In addition, all
      respondents estimated their usage of a LDC health management website would be at
      least once per week, with half indicating a desire to access the website from a
      smartphone. These findings are being used to inform the design of a LDC health
      management website to promote the meaningful involvement of distant family
      members in the care of older adults. 

PMID- 25954470
TI  - Does sustained participation in an online health community affect sentiment?
AB  - A large number of patients rely on online health communities to exchange
      information and psychosocial support with their peers. Examining participation in
      a community and its impact on members' behaviors and attitudes is one of the key
      open research questions in the field of study of online health communities. In
      this paper, we focus on a large public breast cancer community and conduct
      sentiment analysis on all its posts. We investigate the impact of different
      factors on post sentiment, such as time since joining the community, posting
      activity, age of members, and cancer stage of members. We find that there is a
      significant increase in sentiment of posts through time, with different patterns
      of sentiment trends for initial posts in threads and reply posts. Factors each
      play a role; for instance stage-IV members form a particular sub-community with
      patterns of sentiment and usage distinct from others members. 

PMID- 25954471
TI  - On Learning and Visualizing Practice-based Clinical Pathways for Chronic Kidney
      Disease.
AB  - Chronic Kidney Disease (CKD) is a costly and complex disease affecting 20 million
      US adults. Recent studies suggest that care delivery changes may improve clinical
      outcomes and quality of patient experience while reducing costs. This study
      analyzes the treatment data of 8,553 CKD patients to learn practice-based
      clinical pathways. Patients' visit history is modeled as sequences of visits
      containing information on visit type, date, procedures and diagnoses. We use
      hierarchical clustering based on longest common subsequence (LCS) distance to
      discover six patient subgroups, with each subgroup differing in the distribution
      of demographics and health conditions. Transitions of visits with high
      probabilities are elicited from each patient subgroup to learn common clinical
      pathways and treatment durations. Insights from this study can potentially result
      in new evidence to support patient-centered treatment approaches, empower CKD
      patients to better manage their disease and its complications, and provide a
      review guide for clinicians. 

PMID- 25954472
TI  - PubMedMiner: Mining and Visualizing MeSH-based Associations in PubMed.
AB  - The exponential growth of biomedical literature provides the opportunity to
      develop approaches for facilitating the identification of possible relationships
      between biomedical concepts. Indexing by Medical Subject Headings (MeSH)
      represent high-quality summaries of much of this literature that can be used to
      support hypothesis generation and knowledge discovery tasks using techniques such
      as association rule mining. Based on a survey of literature mining tools, a tool
      implemented using Ruby and R - PubMedMiner - was developed in this study for
      mining and visualizing MeSH-based associations for a set of MEDLINE articles. To
      demonstrate PubMedMiner's functionality, a case study was conducted that focused
      on identifying and comparing comorbidities for asthma in children and adults.
      Relative to the tools surveyed, the initial results suggest that PubMedMiner
      provides complementary functionality for summarizing and comparing topics as well
      as identifying potentially new knowledge. 

PMID- 25954473
TI  - Building a co-created citizen science program with gardeners neighboring a
      superfund site: The Gardenroots case study.
AB  - : A research project that is only expert-driven may ignore the role of local
      knowledge in research, give low priority to the development of a comprehensive
      communication strategy to engage the community, and may not deliver the results
      of the study to the community in an effective way. OBJECTIVE: To demonstrate how
      a research program can respond to a community research need, establish a
      community-academic partnership, and build a co-created citizen science program.
      METHODS: A place-based, community-driven project was designed where academics and
      community members maintained a reciprocal dialogue, and together, we: 1) defined
      the question for study, 2) gathered information, 3) developed hypotheses, 3)
      designed data collection methodologies, 4) collected environmental samples (soil,
      irrigation water, and vegetables), 5) interpreted data, 6) disseminated results
      and translated results into action, and 7) discussed results and asked new
      questions. RESULTS: The co-created environmental research project produced new
      data and addressed an additional exposure route (consumption of vegetables grown
      in soils with elevated arsenic levels). Public participation in scientific
      research improved environmental health assessment, information transfer, and risk
      communication efforts. Furthermore, incorporating the community in the scientific
      process produced both individual learning outcomes and community-level outcomes.
      CONCLUSIONS: This approach illustrates the benefits of a community-academic co
      created citizen-science program in addressing the complex problems that arise in
      communities neighboring a contaminated site. Such a project can increase the
      community's involvement in risk communication and decision-making, which
      ultimately has the potential to help mitigate exposure and thereby reduce
      associated risk.

PMID- 25954474
TI  - Multiresistant bacterial infections in liver cirrhosis: Clinical impact and new
      empirical antibiotic treatment policies.
AB  - Recently, important changes have been reported regarding the epidemiology of
      bacterial infections in liver cirrhosis. There is an emergence of multiresistant
      bacteria in many European countries and also worldwide, including the United
      States and South Korea. The classic empirical antibiotic treatment (third
      generation cephalosporins, e.g., ceftriaxone, cefotaxime or amoxicillin
      clavulanic acid) is still effective in infections acquired in the community, but
      its failure rate in hospital acquired infections and in some health-care
      associated infections is high enough to ban its use in these settings. The
      current editorial focuses on the different epidemiology of bacterial infections
      in cirrhosis across countries and on its therapeutic implications. 

PMID- 25954475
TI  - Cognitive dysfunction and hepatitis C virus infection.
AB  - Cognitive dysfunction in patients with chronic hepatitis C virus (HCV) infection
      is a distinct form of minimal hepatic encephalopathy (MHE). In fact, the majority
      of HCV-positive patients, irrespective of the grading of liver fibrosis, display
      alterations of verbal learning, attention, executive function, and memory when
      they are evaluated by suitable neuropsychological tests. Similarities between the
      cognitive dysfunction of HCV patients and MHE of patients with different
      etiologies are unclear. It is also unknown how the metabolic alterations of
      advanced liver diseases interact with the HCV-induced cognitive dysfunction, and
      whether these alterations are reversed by antiviral therapies. HCV replication in
      the brain may play a role in the pathogenesis of neuroinflammation. HCV-related
      brain dysfunction may be associated with white matter neuronal loss, alterations
      of association tracts and perfusion. It is unclear to what extent, in patients
      with cirrhosis, HCV triggers an irreversible neurodegenerative brain damage. New
      insights on this issue will be provided by longitudinal studies using the
      protocols established by the diagnostic and statistical manual of mental
      disorders fifth edition for cognitive disorders. The domains to be evaluated are
      complex attention; executive functions; learning and memory; perceptual motor
      functions; social cognition. These evaluations should be associated with
      fluorodeoxyglucose positron emission tomography and magnetic resonance imaging
      (MRI) protocols for major cognitive disorders including magnetic resonance
      spectroscopy, diffusion tensor imaging, magnetic resonance perfusion, and
      functional MRI. Also, the characteristics of portal hypertension, including the
      extent of liver blood flow and the type of portal shunts, should be evaluated. 

PMID- 25954476
TI  - Primary biliary cirrhosis: Pathophysiology, clinical presentation and therapy.
AB  - Primary biliary cirrhosis (PBC) is an autoimmune, slowly progressive,
      cholestatic, liver disease characterized by a triad of chronic cholestasis,
      circulating anti-mitochondrial antibodies (AMA), and characteristic liver biopsy
      findings of nonsuppurative destructive cholangitis and interlobular bile duct
      destruction. About 10% of PBC patients, however, lack AMA. A variant, called PBC
      autoimmune hepatitis (AIH) overlap, is characterized by the above findings of PBC
      together with findings of elevated serum alanine aminotransferase, elevated serum
      immunoglobulin G, and circulating anti-smooth muscle antibodies, with liver
      biopsy demonstrating periportal or periseptal, lymphocytic, piecemeal necrosis.
      PBC is hypothesized to be related to environmental exposure in genetically
      vulnerable individuals. It typically occurs in middle-aged females. Prominent
      clinical features include fatigue, pruritis, jaundice, xanthomas, osteoporosis,
      and dyslipidemia. The Mayo Risk score is the most widely used and best prognostic
      system. Ursodeoxycholic acid is the primary therapy. It works partly by reducing
      the concentration and injury from relatively toxic bile acids. PBC-AIH overlap
      syndrome is treated with ursodeoxycholic acid and corticosteroids, especially
      budesonide. Obeticholic acid and fibrate are promising new, but incompletely
      tested, therapies. Liver transplantation is the definitive therapy for advanced
      disease, with about 70% 10-year survival after transplantation. Management of
      pruritis includes local skin care, dermatologist referral, avoiding potential
      pruritogens, cholestyramine, and possibly opioid antagonists, sertraline, or
      rifaximin. Management of osteoporosis includes life-style modifications,
      administration of calcium and vitamin D, and alendronate. Statins are relatively
      safe to treat the osteopenia associated with PBC. Associated Sjogren's syndrome
      is treated by artificial tears, cyclosporine ophthalmic emulsion to stimulate
      tear production; and saliva substitutes, cholinergic agents, and scrupulous oral
      and dental care. Complications of cirrhosis from advanced PBC include esophageal
      varices, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, and
      hepatoma formation. 

PMID- 25954477
TI  - Incidence, risk factors and outcome of de novo tumors in liver transplant
      recipients focusing on alcoholic cirrhosis.
AB  - Orthotopic liver transplantation (OLT) is an established life-saving procedure
      for alcoholic cirrhotic (AC) patients, but the incidence of de novo tumors ranges
      between 2.6% and 15.7% and is significantly increased in comparison with patients
      who undergo OLT for other etiologies. Tobacco, a known carcinogen, has been
      reported to be between 52% and 83.3% in AC patients before OLT. Other risk
      factors that contribute to the development of malignancies are dose-dependent
      immunosuppression, advanced age, viral infections, sun exposure, and premalignant
      lesions (inflammatory bowel disease, Barrett's esophagus). A significantly more
      frequent incidence of upper aerodigestive (UAD) tract, lung, skin, and kidney
      bladder tumors has been found in OLT recipients for AC in comparison with other
      etiologies. Liver transplant recipients who develop de novo non-skin tumors have
      a decreased long-term survival rate compared with controls. This significantly
      lower survival rate is more evident in AC recipients who develop UAD tract or
      lung tumors after OLT mainly because the diagnosis is usually performed at an
      advanced stage. All transplant candidates, especially AC patients, should be
      encouraged to cease smoking and alcohol consumption in the pre- and post-OLT
      periods, use skin protection, avoid sun exposure and over-immunosuppression, and
      have a yearly otopharyngolaryngeal exploration and chest computed tomography scan
      in order to prevent or reduce the incidence of de novo malignancies. Although
      still under investigation, substitution of calcineurin inhibitors for sirolimus
      or everolimus may reduce the incidence of de novo tumors after OLT. 

PMID- 25954478
TI  - Hepatitis B reactivation in the setting of chemotherapy and immunosuppression -
      prevention is better than cure.
AB  - Due to the inherent relationship between the immune system and the hepatitis B
      virus (HBV) in exposed and infected individuals, immunomodulation associated with
      the treatment of solid tumours, haematological malignancies and inflammatory
      disorders has been linked to HBV reactivation (HBVr). Reactivation of HBV
      infection in the setting of chemotherapy and immunosuppression may lead to
      fulminant liver failure and death, but there is a cumulative body of evidence
      that these are potentially preventable adverse outcomes. As chronic hepatitis B
      is largely asymptomatic but also endemic worldwide, clinicians caring for
      patients requiring chemotherapy or immunosuppression need to be vigilant of the
      potential for HBVr in susceptible individuals. Serological screening and
      prophylactic and pre-emptive antiviral treatment with a nucleos(t)ide analogue
      should be considered in appropriate settings. Hepatitis B prevalence is examined
      in this review article, as are the risks of HBVr in patients receiving chemo- and
      immunosuppressive therapy. Recommendations regarding screening, monitoring and
      the role of antiviral prophylaxis are outlined with reference to current
      international associations' guidelines and the best available evidence to date. 

PMID- 25954481
TI  - Acute kidney injury in patients with chronic liver disease.
AB  - Acute kidney injury (AKI) is a frequent clinical event in patients with liver
      disease, compounding their prognosis. Furthermore, it is likely that the
      occurrence of AKI has a detrimental impact on the subsequent renal function and
      the long-term survival of these patients. Recently, some authors advocated the
      use of new diagnostic criteria for detecting acute kidney injury in patients with
      cirrhosis. These criteria are based on the rapidity and extent of the creatinine
      increase comparing to the basal creatinine and also on the kinetics of diuresis
      decrease. Although their validity in this population requires further studies to
      be clearly established, these new criteria could have two advantages: (1) to
      allow earlier diagnosis of AKI and, thus, hepatorenal syndrome for which earlier
      intervention could improve patients' survival; and (2) to promote more intensive
      monitoring of renal function in these patients with high risk of AKI. Finally,
      recent practice guidelines about the prevention and treatment of general AKI have
      been published which should be useful in optimising the management of AKI in
      cirrhotic patients. 

PMID- 25954479
TI  - Control of oxidative stress in hepatocellular carcinoma: Helpful or harmful?
AB  - Oxidative stress is becoming recognized as a key factor in the progression of
      chronic liver disease (CLD) and hepatocarcinogenesis. The metabolically important
      liver is a major reservoir of mitochondria that serve as sources of reactive
      oxygen species, which are apparently responsible for the initiation of
      necroinflammation. As a result, CLD could be a major inducer of oxidative stress.
      Chronic hepatitis C is a powerful generator of oxidative stress, causing a high
      rate of hepatocarcinogenesis among patients with cirrhosis. Non-alcoholic
      steatohepatitis is also associated with oxidative stress although its
      hepatocarcinogenic potential is lower than that of chronic hepatitis C. Analyses
      of serum markers and histological findings have shown that hepatocellular
      carcinoma correlates with oxidative stress and experimental data indicate that
      oxidative stress increases the likelihood of developing hepatocarcinogenesis.
      However, the results of antioxidant therapy have not been favorable.
      Physiological oxidative stress is a necessary biological response, and thus
      adequate control of oxidative stress and a balance between oxidative and anti
      oxidative responses is important. Several agents including metformin and L
      carnitine can reportedly control mechanistic oxidative stress. This study reviews
      the importance of oxidative stress in hepatocarcinogenesis and of control
      strategies for the optimal survival of patients with CLD and hepatocellular
      carcinoma. 

PMID- 25954482
TI  - Mean platelet volume as a novel predictor of systemic inflammatory response in
      cirrhotic patients with culture-negative neutrocytic ascites.
AB  - AIM: To identify a mean platelet volume (MPV) cutoff value which should be able
      to predict the presence of bacterial infection. METHODS: An observational,
      analytic, retrospective study. We evaluated medical records of cirrhotic patients
      who were hospitalized from January 2012 to January 2014 at the Gastroenterology
      Department of "Hospital General de Mexico Dr. Eduardo Liceaga", we included 51
      cirrhotic patients with ascites fluid infection (AFI), and 50 non-infected
      cirrhotic patients as control group. Receiver operator characteristic curves were
      used to identify the best cutoff value of several parameters from hematic
      cytometry, including MPV, to predict the presence of ascites fluid infection.
      RESULTS: Of the 51 cases with AFI, 48 patients (94.1%) had culture-negative
      neutrocytic ascites (CNNA), 2 (3.9%) had bacterial ascites, and one (2%) had
      spontaneous bacterial peritonitis. Infected patients had greater count of
      leucocytes and polymorphonuclear cells, greater levels of MPV and cardiac
      frequency (P < 0.0001), and lower mean arterial pressure compared with non
      infected patients (P = 0.009). Leucocytes, polymorphonuclear count, MPV and
      cardiac frequency resulted to be good or very good predictive variables of
      presence of AFI in cirrhotic patients (area under the receiving operating
      characteristic > 0.80). A cutoff MPV value of 8.3 fl was the best to discriminate
      between cirrhotic patients with AFI and those without infection. CONCLUSION: Our
      results support that MPV can be an useful predictor of systemic inflammatory
      response syndrome in cirrhotic patients with AFI, particularly CNNA.

PMID- 25954483
TI  - Hyperammonemia-induced encephalopathy: A rare devastating complication of
      bariatric surgery.
AB  - The clinical manifestations of hyperammonemia are usually easily identifiable to
      the clinician when associated with liver disease and lead to prompt diagnosis and
      treatment. However, hyperammonemia-induced encephalopathy is rare in adults in
      the absence of overt liver disease, thus diagnosis is often delayed or missed
      leading to potentially life threatening complications. Without proper treatment,
      such patients can decompensate rapidly with poor outcomes including seizures,
      coma, and death. Early assessment of plasma ammonia levels in patients with
      normal hepatic function and characteristic symptoms of encephalopathy can lead to
      early intervention while investigating the underlying etiology. We describe a
      patient who presented with a 2-year progression of waxing and waning acute mental
      status changes after a Roux-en-Y gastric bypass surgery. He was found to have
      elevated ammonia level as well as orotic aciduria; results consistent with a urea
      cycle disorder. After consulting neurology as well as toxicology, he ultimately
      improved after dietary protein restriction, sodium benzoate and lactulose
      therapy. While rare, clinicians should have a high index of suspicion for late
      onset urea cycle disorders in symptomatic patients presenting with encephalopathy
      secondary to hyperammonemia. 

PMID- 25954480
TI  - Immunotherapy for hepatocellular carcinoma: From basic research to clinical use.
AB  - Hepatocellular carcinoma (HCC) is a common cancer worldwide with a poor
      prognosis. Few strategies have been proven efficient in HCC treatment,
      particularly for those patients not indicated for curative resection or
      transplantation. Immunotherapy has been developed for decades for cancer control
      and is attaining more attention as a result of encouraging outcomes of new
      strategies such as chimeric antigen receptor T cells and immune checkpoint
      blockade. Right at the front of the new era of immunotherapy, we review the
      immunotherapy in HCC treatment, from basic research to clinical trials, covering
      anything from immunomodulators, tumor vaccines and adoptive immunotherapy. The
      mechanisms, efficacy and safety as well as the approach particulars are unveiled
      to assist readers to gain a concise but extensive understanding of immunotherapy
      of HCC. 

PMID- 25954485
TI  - Using recombinant Chlamydia trachomatis OMP2 as antigen in diagnostic ELISA test.
AB  - BACKGROUND AND OBJECTIVES: The obligate intracellular bacterium Chlamydia
      trachomatis causes sexually transmissible diseases in human. Timely and sensitive
      detection of this pathogen is very important. There are many cross-reactions in
      bacteriological and serological methods in detection of this type of pathogens.
      The aim of this study was to achieve a more specific antigen for serological
      tests. MATERIALS AND METHODS: Blood samples were taken from 192 women with
      suspected chlamydial infection and sera were isolated. ELISA plate wells were
      coated with recombinant C. trachomatis OMP2 as antigen. Cut-off system was
      determined with 40 negative sera. The final results of this research were
      compared with Euroimmun commercial kit. RESULTS: The ELISA system cut-off was
      calculated at 0.27 using negative sera samples. ODs of positive samples were
      higher than 0.27 and negative samples were lower than it. We obtained 30 samples
      (15.62%) as positive and 162 cases (84.37%) as negative. Sensitivity and
      specificity of the recombinant antigen were 90% and 86%, respectively. This
      antigen showed no cross-reactivity with sera of patients infected with Hydatid
      cyst, HCV, Epstein barr virus, HBV, Helicobacter pylori, Toxoplasma gondii,
      Cytomegalovirus, Mycoplasma, Measles and Varicella zoster virus. CONCLUSION: The
      sensitivity and specificity of rOMP2 in ELISA for detection of C. trachomatis
      were 90% and 86%, respectively. Though the sensitivity was higher than results of
      Euroimmun commercial kit, its specificity was calculated lower than reference
      kit.

PMID- 25954484
TI  - Heterogeneity of Iranian clinical isolates of Mycobacterium fortuitum.
AB  - BACKGROUND AND OBJECTIVES: The increase of infections caused by nontuberculous
      mycobacteria (NTM) is receiving increasing attention worldwide. Mycobacterium
      fortuitum is encountered with increasing frequency in clinical laboratories of
      Iran. MATERIALS AND METHODS: Sequence variation of 48 M. fortuitum clinical
      isolates, were investigated by sequence analysis of the 16S-23S Internal
      Transcribed Spacer. RESULTS: Twelve different sequence types (sequevar) were
      identified by sequence analysis of ITS region. Seven previously described
      sequevar including MfoA, MfoB, MfoC, MfoD, MfoE, MfoF and MfoG identified. Five
      novel sequevar namely MfoH, MfoI, MfoJ, MfoK and MfoL that were distinctly
      different from the previously described sequevar were detected among different
      clinical strains of M. fortuitum, from Iran. CONCLUSION: This study showed that
      the ITS region possesses high discriminatory power between the clinical isolates
      up to the clonal level. The results also suggest the possibility of the existence
      of predominant clone of M. fortuitum in affected patients in Iran. The data also
      point to the conclusion that a large variety of M. fortuitum clone can produce
      disease although certain clones seem to be predominant.

PMID- 25954486
TI  - Prevalence of Helicobacter pylori vacA, cagA, cagE, iceA, babA2, and oipA
      genotypes in patients with upper gastrointestinal diseases.
AB  - BACKGROUND AND OBJECTIVES: Helicobacter pylori has been strongly associated with
      peptic ulcer diseases, chronic gastritis, ulcers, and reported as a risk factor
      for gastric cancer, too. The vaculating cytotoxin (vacA), the cytotoxin
      associated genes (cagA), the induced by contact with epithelium factor antigen
      (iceA gene), blood adhesion binding antigen (babA2), and outer membrane protein
      oipA have been described as different virulence factors of H. pylori. The aim of
      this study was to investigate the prevalence of the vacA, cagA, cagE, iceA, babA2
      and oipA genotypes of H. pylori isolates from patients with upper
      gasterointestinal problem or dyspepsia. MATERIAL AND METHODS: H. pylori isolated
      from endoscopic biopsies obtained from 222 studied patients. PCR was done only on
      cultured positive samples. The vacA alleles, cagA, cagE, iceA, babA2 and oipA
      genotypes were determined by PCR. RESULTS: The isolation rate of H. pylori
      strains from culture of gastric biopsies was 16.7%. The vacA alleles s1, s2, m1
      and m2 were detected in 20 (54.1%), 14 (37.8%), 9 (24.3%) and 23 (62.2%)
      isolates, respectively. VacA s1c genotype was detected in 70.3% of isolates. s1m2
      was the most frequent vacA allelic combination in the examined H. pylori strains.
      The cagA gene was detected in 62.2%, cagE in 40.5%, iceA1 in 48.6%, iceA2 in
      16.2%, oipA in 81.1% (95% CI: 0.0902-0.1798) and babA2 in 94.6% (95% CI: 0.113-
      0.207). A significant correlation was observed between vacAs1 and cagA genotypes
      (P<0.008), vacAs1/cagE (P=0.001), vacAs2/cagA (P<0.047), and vacAs2/cagE
      (P=0.016) with Non-ulcer dyspepsia; but there were not observed any correlation
      between other virulence markers. CONCLUSION: No significant correlation was found
      between the existence of vacA, cagA, cagE, iceA, babA2, and oipA genes with
      peptic ulcer diseases and non-ulcer dyspepsia groups of studied patients.

PMID- 25954487
TI  - Prevalence of metalo- beta-lactamase-producing (MBL) Acinetobacter species in a
      tertiary care hospital.
AB  - BACKGROUND AND OBJECTIVES: Acinetobacter causes a wide variety of illness in
      debilitated and hospitalized patients. Carbapenem resistance in Acinetobacter is
      an emerging problem and is a cause of concern as many nosocomial infections with
      Acinetobacter are resistant to most other antibiotics. The present study was
      aimed to study metallo-beta-lactamase (MBL) production in Acinetobacter species.
      MATERIALS AND METHODS: During one year prospective study, all isolates of
      Acinetobacter obtained from various clinical samples like respiratory, pus, blood
      and others were included. Antimicrobial susceptibility testing was done by
      standard Kirby Bauer disk diffusion method. Metallo beta-lactamase (MBL)
      detection was done by imipenem-EDTA combined disk method. RESULTS: Among 1017
      isolates, 964 were A. baumannii, 48 were A. lwoffii and 5 were A. hemolyticus.
      Out of these, majority of the isolates were obtained from respiratory samples,
      followed by pus. A .baumannii showed high level of resistance to cephalosporins,
      cotrimoxazole and piperacillin. A .lwoffii and A. hemolyticus showed lesser
      resistance to all antibiotics. Imipenem resistance was observed in 389 (40.3 %)
      isolates of A.baumannii and MBL activity was seen in 80.3% of isolates. MBL
      positive isolates of A. baumannii showed higher resistance as compared to MBL
      negative isolates. CONCLUSION: This study demonstrated that multidrug resistant
      strains of Acinetobacter are common in tertiary care hospitals. Unwarranted and
      unrestricted usage of antibiotics is associated with emergence of resistance in
      nosocomial pathogens. Regular monitoring and documentation of carbapenem
      resistant is crucial in developing strategies to control infection due to these
      bacteria.

PMID- 25954488
TI  - In vitro comparison of the antibacterial effect of three intracanal irrigants and
      diode laser on root canals infected with Enterococcus faecalis.
AB  - INTRODUCTION: Bacteria are the primary etiology of pulpal and periradicular
      pathosis. In endodontically treated teeth with persistent infections only one or
      a few bacterial species are present of which the most important is Enterococcus
      faecalis. The aim of this study was to compare antibacterial efficacy of canal
      disinfectants including 5.25% sodium hypochlorite, 2% chlorhexidine, MTAD (a
      mixture of doxycycline, citric acid and a detergent (Tween 80) and 830 nm diode
      laser. METHODS AND MATERIALS: The canals of 135 extracted single rooted human
      teeth were prepared using rotary instruments. The canals were contaminated with
      Enterococcus faecalis for 4 weeks and then were divided into 4 groups of 30 teeth
      in each, a positive control group containing 10 teeth and a negative control
      group of 5 teeth. After using the disinfectants, samples obtained from canals by
      paper points and also shaving the canal walls were cultured. The Kruskal-Wallis
      test was used to analyze the results. RESULTS: The results showed the bacterial
      reduction as follows: 99.97+/-0.14 for sodium hypochlorite, 99.65+/-1.13 for
      chlorhexidine, 97.56+/-6.36 for laser and 96.91+/-5.60 for MTAD. The count of CFU
      obtained from dentin shavings was: 16/96+/-91/23 for sodium hypochlorite, 82/73+/
      186/63 .for chlorhexidine, 47/26+/-112/21 for laser and 341/34+/-1139/83 for
      MTAD. CONCLUSION: According to the results, sodium hypochlorite was the most
      effective agent against Enterococcus faecalis.

PMID- 25954489
TI  - Genotyping of Clostridium perfringens isolated from healthy and diseased
      ostriches (Struthio camelus).
AB  - BACKGROUND AND OBJECTIVES: Clostridium perfringens is more prevalent type of
      clostridia genus isolated from the intestinal tract of ostrich (Struthio
      camelus). Necrotic enteritis (NE) is a potentially fatal gastrointestinal (GI)
      disease of poultry and other avian species, which produces marked destruction of
      intestinal lining in digestive tract caused by C. perfringens. Pathogenicity and
      lesions are correlated with the toxins produced, thus toxin typing of the
      bacterium has diagnostic and epidemiological significance. The aims of the
      present study were to determine the biotypes of C. perfringens among ostrich's
      farms either diseased and healthy ones and to screen the isolates for major toxin
      genes (cpa, cpb, etx, and iA, cpb2, and cpe). MATERIALS AND METHODS: Thirty
      isolates of C. perfringens were obtained from NE-positive and NE-negative ostrich
      flocks in Khorasan-e-Razavi porvince and analyzed by multiplex PCR assay.
      RESULTS: All isolates were positive for alpha toxin gene (cpa) and five of those
      were positive for beta toxin gene (cpb). The presence of cpb2 gene was detected
      in a high percentage of isolates originating from both healthy (93.3%) and
      diseased flocks (80%). None of the isolate carried enterotoxin gene (cpe).
      CONCLUSION: The results suggest that types A and C of C. perfringens are the most
      prevalent types in ostrich in Iran. Due to detection of beta2 toxin gene in
      isolates from both healthy and diseased birds, it appears that the presence of
      cpb2 is not considered a risk by itself.

PMID- 25954490
TI  - Seroprevalence of varicella-zoster virus among pregnant women in two teaching
      hospitals, Tehran, Iran.
AB  - BACKGROUND AND OBJECTIVES: Varicella zoster virus (VZV) can cause life
      threatening disease in pregnant women. The aim of this study was to identify the
      VZV immune status in pregnant women and also determine the validity of self
      reported history for chickenpox. METHODS: Serologic testing for VZV was performed
      for 400 pregnant women attending prenatal care at clinics located in two teaching
      and referral hospitals in Tehran, Iran. The Enzyme Immunoassay method was used to
      assess IgG antibodies against VZV. RESULTS: A total of 400 pregnant women, aged
      16-43 years (median: 27 years, mean: 27.6 +/- 5.9 years), were examined in which
      361 (90.3%) were found to be seropositive. Sensitivity, specificity and positive
      and negative predictive values of patients' self reported history were 51.8%,
      71.7%, 94.4% and 13.8% respectively. CONCLUSION: Serologic screening for VZV in
      pregnant women seems crucial. We suggest considering the pregnant women as the
      target group for future immunization programs in Iran.

PMID- 25954491
TI  - Inactivation of model viruses suspended in fresh frozen plasma using novel
      methylene blue based device.
AB  - BACKGROUND AND OBJECTIVE: There is a concern on safety of human Fresh Frozen
      Plasma (FFP) as it is a source of some medicinal products. The possibility of
      transmission of blood-borne are reported often due to emerging viruses. There are
      some Pathogen Reduction Technologies (PRT) to inactivate viruses. Methylene Blue
      (MB) based method is one of them. The aim of this study was to examine new
      designated device to inactivate model viruses. MATERIALS AND METHODS: Four model
      viruses were used in this study:Vesicular stomatitis virus (VSV), Herpes Simplex
      Virus I (HSV-1), Bovine Viral DiarrheaVirus(BVDV) and Polio Virus.50% Tissue
      Culture Infective Dose (TCID 50) and Reed-Muench Methods were used to titer the
      viruses. MB in two final concentration of 0.1 MUM and 1 MUM and illumination in
      about 627nm with red LED (Lamp Emitting Diode) for 15, 30, 45 and 60 minutes were
      used. Three replicates employed for each experiments. RESULTS: 1MUMconcentration
      of MB showed more effective than 0.1MUMin all designed illumination period for
      inactivation of HSV, VSV and BVDV. This method also demonstrated best results for
      enveloped model viruses. The most Log reduction for HSV, VSV and BVDV were6.28,
      5.54 and 6.22, respectively. For HSV and BVDV inactivation, the best illumination
      period was 45 minutes. CONCLUSION: Model viruses showed sensitivity combination
      of MB and illumination using red LEDs. As results show this device could
      inactivate model viruses and reduce their titer very close to approved commercial
      devices, in compare.

PMID- 25954492
TI  - Fungal flora of the combs and wattles of Iranian native chickens.
AB  - BACKGROUND AND OBJECTIVES: Poultry are more susceptible to receiving and
      spreading of fungal infections in exact conditions. The goal of this study was to
      identify the normal fungal flora and dermatophytes agent of the combs and wattles
      of adult native chickens in Tehran, Iran. MATERIALS AND METHODS: A total of 150
      combs and wattles samples were collected by skin scraping or brushing of the
      margin of the suspected lesion and skin of organ. The mycological analyses were
      performed by direct microscopy and culture media. RESULTS: One hundred and ninety
      fungi were isolated from the combs of 150 native chickens' samples that including
      non-dermatophytes isolates 165 (86.8%), dermatophytes 6 (3.2%) and yeast 19
      (10%). Among different fungal isolates, Aspergillus was the predominant species.
      CONCLUSION: Our results showed that human in contact with poultry, both at the
      household and the industrial level, have a clear risk factor for exposure to
      fungal pathogens, especially dermatophytes.

PMID- 25954493
TI  - The effects of sonication and gamma irradiation on the inactivation of
      Escherichia coli and Saccharomyces cerevisiae in pomegranate juice.
AB  - BACKGROUND AND OBJECTIVES: Pomegranate fruit is a rich source of bioactive
      compounds. The serious concern over unprocessed fruit juices is microbial
      contamination, which effectively inactivated by thermal processing, but it
      significantly affects juice functional compounds. Therefore, the effect of gamma
      irradiation and ultrasonic on inoculated microbial to pomegranate juices was
      studied. MATERIALS AND METHODS: Two pomegranate cultivars were purchased from the
      Agricultural Research Center of Saveh, and their juices were extracted by a
      manual device and immediately centrifuged. Then the studied microorganisms were
      re-suspended in sterile pomegranate juices. The juices were continuously
      sonicated at amplitude levels of 50, 75 and 100% and times of 0, 3, 6, 9, 12 and
      15 min at temperature of 25 +/- 1  degrees C. Irradiation treatment was also
      carried out at various doses of 0, 0.5, 1.0, 1.5, 2.0, 2.5 and 3 kGy. RESULTS:
      The results showed that lower amplitude levels (50 and 75%) did not inactivate E.
      coli and S. cerevisiae significantly (<1.5 log reduction), while at 100%
      amplitude level for 15 min, their population reduced by 3.47 and 1.86 log cfu/mL,
      respectively. Gamma irradiation treatment at 1 kGy also reduced E. coli by 6.66
      log cfu/mL, whereas at 3 kGy it reduced S. cerevisiae by 5.08 log cfu/mL.
      CONCLUSIONS: The low-dose gamma irradiation could potentially inactivate the
      studied microorganisms compared to the sonication, which had less destructive
      effects on their populations. Further research is needed to determine the effect
      of these methods on other fruit juices for industry purposes.

PMID- 25954494
TI  - Erratum.
AB  - [This corrects the article on p. 220 in vol. 5, PMID: 24475327.]. 

PMID- 25954495
TI  - Ketamine and other N-methyl-D-aspartate receptor antagonists in the treatment of
      depression: a perspective review.
AB  - Current pharmacotherapies for major depressive disorder (MDD) and bipolar
      depression (BDep) have a distinct lag of onset that can generate great distress
      and impairment in patients. Furthermore, as demonstrated by several real-world
      effectiveness trials, their efficacy is limited. All approved antidepressant
      medications for MDD primarily act through monoaminergic mechanisms, agonists or
      antagonists with varying affinities for serotonin, norepinephrine and dopamine.
      The glutamate system has received much attention in recent years as an avenue for
      developing novel therapeutics. A single subanesthetic dose infusion of the
      noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has been
      shown to have rapid and potent antidepressant effects in treatment-resistant MDD
      and BDep. In a reverse translational framework, ketamine's clinical efficacy has
      inspired many preclinical studies to explore glutamatergic mechanisms of
      antidepressant action. These studies have revealed enhanced synaptic
      plasticity/synaptogenesis via numerous molecular and cellular mechanisms: release
      of local translational inhibition of brain-derived neurotrophic factor and
      secretion from dendritic spines, mammalian target of rapamycin activation and
      glycogen synthase kinase-3 inhibition. Current efforts are focused on extending
      ketamine's antidepressant efficacy, uncovering the neurobiological mechanisms
      responsible for ketamine's antidepressant activity in biologically enriched
      subgroups, and identifying treatment response biomarkers to personalize
      antidepressant selection. Other NMDA receptor antagonists have been studied both
      preclinically and clinically, which have revealed relatively modest
      antidepressant effects compared with ketamine but potentially other favorable
      characteristics, for example, decreased dissociative or psychotomimetic effects;
      therefore, there is great interest in developing novel glutamatergic
      antidepressants with greater target specificity and/or decreased adverse effects.

PMID- 25954496
TI  - The diagnosis and treatment of chronic migraine.
AB  - Migraine is the most common disabling brain disorder. Chronic migraine, a
      condition characterized by the experience of migrainous headache on at least 15
      days per month, is highly disabling. Patients with chronic migraine present to
      primary care, are often referred for management to secondary care, and make up a
      large proportion of patients in specialist headache clinics. Many patients with
      chronic migraine also have medication overuse, defined as using a compound
      analgesic, opioid, triptan or ergot derivative on at least 10 days per month. All
      doctors will encounter patients with chronic headaches. A basic working knowledge
      of the common primary headaches, and a rational manner of approaching the patient
      with these conditions, allows a specific diagnosis of chronic migraine to be made
      quickly and safely, and by making this diagnosis one opens up a substantial
      number of acute and preventive treatment options. This article discusses the
      current state of management of chronic migraine. 

PMID- 25954497
TI  - Management of cirrhotic ascites.
AB  - The most common complication to chronic liver failure is ascites. The formation
      of ascites in the cirrhotic patient is caused by a complex chain of
      pathophysiological events involving portal hypertension and progressive vascular
      dysfunction. Since ascites formation represents a hallmark in the natural history
      of chronic liver failure it predicts a poor outcome with a 50% mortality rate
      within 3 years. Patients with ascites are at high risk of developing
      complications such as spontaneous bacterial peritonitis, hyponatremia and
      progressive renal impairment. Adequate management of cirrhotic ascites and its
      complications betters quality of life and increases survival. This paper
      summarizes the pathophysiology behind cirrhotic ascites and the diagnostic
      approaches, as well as outlining the current treatment options. Despite improved
      medical treatment of ascites, liver transplantation remains the ultimate
      treatment and early referral of the patient to a highly specialized hepatology
      unit should always be considered. 

PMID- 25954498
TI  - Optimizing the use of thiopurines in inflammatory bowel disease.
AB  - Immunomodulator drugs, of which thiopurines can be considered the backbone, are
      widely used in the treatment of inflammatory bowel disease. They have been shown
      to be highly effective and safe; however, a significant proportion of patients
      are deemed to have a poor response or suffer adverse reactions. Knowing how to
      monitor and optimize thiopurine therapy in these scenarios is crucial to
      effective management. We discuss the metabolism of thiopurines, the use of
      enzyme/metabolite testing to guide treatment, as well as strategies to circumvent
      toxicity and side effects, such as allopurinol coprescription. The indications,
      use in pregnancy, safety profile and duration of thiopurine therapy are also
      discussed. 

PMID- 25954499
TI  - Optimizing the use of anti-tumor necrosis factor in the management of patients
      with Crohn's disease.
AB  - Since the approval of the first anti-tumor necrosis factor (anti-TNF) therapy in
      late 1998, the treatment for Crohn's disease (CD) has been revolutionized. Anti
      TNF therapy has been consistently shown in numerous clinical trials to be
      effective for patients with more aggressive perianal, internal penetrating, and
      fistulizing CD. However, the loss of clinical remission is frequent and only one
      third of patients remain in clinical remission at 1 year. The pharmacokinetics of
      anti-TNF is highly variable among patients and could be influenced by many
      factors including serum albumin, gender, body weight, systemic inflammation and
      route of administration. The main factor impacting anti-TNF pharmacokinetics and
      efficacy is the development of immunogenicity where antidrug antibodies
      accelerate anti-TNF drug clearance. In this review paper, we evaluate the role of
      combination therapy with anti-TNF drugs and immunomodulators, the role of
      therapeutic drug monitoring, and strategies to recapture loss of clinical
      response in order to improve both short- and long-term outcomes in CD patients. 

PMID- 25954500
TI  - Measuring acoustic habitats.
AB  - 1. Many organisms depend on sound for communication, predator/prey detection and
      navigation. The acoustic environment can therefore play an important role in
      ecosystem dynamics and evolution. A growing number of studies are documenting
      acoustic habitats and their influences on animal development, behaviour,
      physiology and spatial ecology, which has led to increasing demand for passive
      acoustic monitoring (PAM) expertise in the life sciences. However, as yet, there
      has been no synthesis of data processing methods for acoustic habitat monitoring,
      which presents an unnecessary obstacle to would-be PAM analysts. 2. Here, we
      review the signal processing techniques needed to produce calibrated measurements
      of terrestrial and aquatic acoustic habitats. We include a supplemental tutorial
      and template computer codes in matlab and r, which give detailed guidance on how
      to produce calibrated spectrograms and statistical analyses of sound levels. Key
      metrics and terminology for the characterisation of biotic, abiotic and
      anthropogenic sound are covered, and their application to relevant monitoring
      scenarios is illustrated through example data sets. To inform study design and
      hardware selection, we also include an up-to-date overview of terrestrial and
      aquatic PAM instruments. 3. Monitoring of acoustic habitats at large
      spatiotemporal scales is becoming possible through recent advances in PAM
      technology. This will enhance our understanding of the role of sound in the
      spatial ecology of acoustically sensitive species and inform spatial planning to
      mitigate the rising influence of anthropogenic noise in these ecosystems. As we
      demonstrate in this work, progress in these areas will depend upon the
      application of consistent and appropriate PAM methodologies.

PMID- 25954502
TI  - In vitro stability of therapeutically relevant, internally truncated dystrophins.
AB  - BACKGROUND: The X-linked recessive disease Duchenne muscular dystrophy (DMD) is
      caused by mutations in the gene encoding the protein dystrophin. Despite its
      large size, dystrophin is a highly stable protein, demonstrating cooperative
      unfolding during thermal denaturation as monitored by circular dichroism
      spectroscopy. In contrast, internal sequence deletions have been associated with
      a loss of the cooperative unfolding and cause in vitro protein aggregation.
      Several emerging therapy options for DMD utilize internally deleted micro
      dystrophins and multi-exon-skipped dystrophins that produce partially functional
      proteins, but the stability of such internally truncated proteins has not been
      investigated. METHODS: In this study, we analyzed the in vitro stability of human
      dystrophin constructs skipped around exon 45 or exon 51, several dystrophin gene
      therapy constructs, as well as human full-length and micro-utrophin. Constructs
      were expressed in insect cells using the baculovirus system, purified by affinity
      chromatography, and analyzed by high-speed sedimentation, circular dichroism
      spectroscopy, and differential scanning fluorimetry. RESULTS: Our results reveal
      that not all gene therapy constructs display stabilities consistent with full
      length human dystrophin. However, all dystrophins skipped in-frame around exon 45
      or exon 51 show stability profiles congruent with intact human dystrophin.
      Similar to previous studies of mouse proteins, full-length human utrophin also
      displays stability similar to human dystrophin and does not appear to be affected
      by a large internal deletion. CONCLUSIONS: Our results suggest that the in vitro
      stability of human dystrophin is less sensitive to smaller deletions at natural
      exon boundaries than larger, more complex deletions present in some gene therapy
      constructs.

PMID- 25954501
TI  - The Nodal signaling pathway controls left-right asymmetric development in
      amphioxus.
AB  - BACKGROUND: Nodal is an important determinant of the left-right (LR) body axis in
      bilaterians, specifying the right side in protostomes and non-chordate
      deuterostomes as opposed to the left side in chordates. Amphioxus represents an
      early-branching chordate group, rendering it especially useful for studying the
      character states that predate the origin of vertebrates. However, its anatomy,
      involving offset arrangement of axial structures, marked asymmetry of the
      oropharyngeal region, and, most notably, a mouth positioned on the left side,
      contrasts with the symmetric arrangement of the corresponding regions in other
      chordates. RESULTS: We show that the Nodal signaling pathway acts to specify the
      LR axis in the cephalochordate amphioxus in a similar way as in vertebrates. At
      early neurula stages, Nodal switches from initial bilateral to the left-sided
      expression and subsequently specifies the left embryonic side. Perturbation of
      Nodal signaling with small chemical inhibitors (SB505124 and SB431542) alters
      expression of other members of the pathway and of left/right-sided, organ
      specific genes. Upon inhibition, larvae display loss of the innate alternation of
      both somites and axons of peripheral nerves and loss of left-sided pharyngeal
      structures, such as the mouth, the preoral pit, and the duct of the club-shaped
      gland. Concomitantly, the left side displays ectopic expression of otherwise
      right-sided genes, and the larvae exhibit bilaterally symmetrical morphology,
      with duplicated endostyle and club-shaped gland structures. CONCLUSIONS: We
      demonstrate that Nodal signaling is necessary for establishing the LR embryonic
      axis and for developing profound asymmetry in amphioxus. Our data suggest that
      initial symmetry breaking in amphioxus and propagation of the pathway on the left
      side correspond with the situation in vertebrates. However, the organs that
      become targets of the pathway differ between amphioxus and vertebrates, which may
      explain the pronounced asymmetry of its oropharyngeal and axial structures and
      the left-sided position of the mouth.

PMID- 25954503
TI  - The promise of stem cells in the therapy of Alzheimer's disease.
AB  - Alzheimer's disease (AD), a common neurodegenerative disorder associated with
      gradually to dramatic neuronal death, synaptic loss and dementia, is considered
      to be one of the most obscure and intractable brain disorders in medicine.
      Currently, there is no therapy clinically available to induce marked symptomatic
      relief in AD patients. In recent years, the proof-of-concept studies using stem
      cell-based approaches in transgenic AD animal models provide new hope to develop
      stem cell-based therapies for the effective treatment of AD. The degeneration of
      basal forebrain cholinergic neurons (BFCNs) and the resultant cholinergic
      abnormalities in the brain contribute substantially to the cognitive decline of
      AD patients. The approches using stem cell-derived BFCNs as donor cells need to
      be developed, and to provide proof of principle that this subtype-specific
      neurons can induce functional recovery of AD animal models. With the continuous
      scientific advances in both academic and industrial fields, the potentials of
      stem cells in cellular neuroprotection and cell replacement in vivo have been
      elucidated, and stem cell-based therapy for repairing degenerative brains of AD
      is promising. 

PMID- 25954504
TI  - Study and use of the probiotic Lactobacillus reuteri in pigs: a review.
AB  - Probiotics are living microorganisms that provide a wide variety of health
      benefits to the host when ingested in adequate amounts. The bacterial strains
      most frequently used as probiotic agents are lactic acid bacteria, such as
      Lactobacillus reuteri, which is one of the few endogenous Lactobacillus species
      found in the gastrointestinal tract of vertebrates, including humans, rats, pigs
      and chickens. L. reuteri is one of the most well documented probiotic species and
      has been widely utilized as a probiotic in humans and animals for many years.
      Initially, L. reuteri was used in humans to reduce the incidence and the severity
      of diarrhea, prevent colic and necrotic enterocolitis, and maintain a functional
      mucosal barrier. As interest in alternatives to in-feed antibiotics has grown in
      recent years, some evidence has emerged that probiotics may promote growth,
      improve the efficiency of feed utilization, prevent diarrhea, and regulate the
      immune system in pigs. In this review, the characteristics of L. reuteri are
      described, in order to update the evidence on the efficacy of using L. reuteri in
      pigs. 

PMID- 25954505
TI  - The burden of disease on HIV-infected orphaned and non-orphaned children
      accessing primary health facilities in a rural district with poor resources in
      South Africa: a cross-sectional survey of primary caregivers of HIV-infected
      children aged 5-18 years.
AB  - BACKGROUND: Provider-initiated HIV testing and counseling (PITC) is offered as
      part of the normal standard of care to increase access to treatment for HIV
      infected children. In practice, HIV diagnosis occurs in late childhood following
      recurrent and chronic infections. We investigated primary caregivers' reported
      reasons for seeking HIV testing for children aged 5-18 years, determined the
      orphan status of the children, and compared the clinical profile and disease
      burden of orphans and non-orphans. METHODS: This was a cross-sectional survey of
      primary caregivers of HIV-infected children accessing antiretroviral treatment
      (ART) from two community hospitals and 34 primary healthcare facilities in a
      rural district in Mpumalanga province, South Africa. RESULTS: The sample
      consisted of 406 primary caregivers: 319 (78.6%) brought the child to the health
      facility for HIV testing because of chronic and recurrent infections. Almost half
      (n = 183, 45.1%) of the children were maternal orphans, 128 (31.5%) were paternal
      orphans, and 73 (39.9%) were double orphans. A univariate analysis showed that
      maternal orphans were significantly more likely to be older (OR = 2.57, p =
      0.000, CI: 1.71-3.84), diagnosed late (OR = 2.48, p = 0.009, CI: 1.26-4.88), and
      to start ART later (OR = 2.5, p = 0.007, CI: 1.28-4.89) than non-orphans. There
      was a high burden of infection among the children prior to HIV diagnosis; 274
      (69.4%) presented with multiple infections. Multiple logistic regression showed
      that ART start age (aOR = 1.19, p = 0.000, CI: 1.10-1.29) and time on ART (aOR =
      2.30, p = 0.000, CI: 1.45-3.64) were significantly associated with orphanhood
      status. Half (n = 203, (50.2%) of the children were admitted to hospital prior to
      start of ART, and hospitalization was associated with multiple infections (OR =
      1.27, p = 0.004, CI: 1.07-1.51). CONCLUSIONS: The study found late presentation
      with undiagnosed perinatal HIV infection and high prevalence of orphanhood among
      the children. The health of maternal orphans was more compromised than non
      orphans. Routine PICT should be strengthened to increase community awareness
      about undiagnosed HIV among older children and to encourage primary caregivers to
      accept HIV testing for children.

PMID- 25954506
TI  - Profiling B and T cell immune responses to co-infection of Mycobacterium
      tuberculosis and hookworm in humans.
AB  - BACKGROUND: Humoral and cellular immune responses play protective roles against
      Mycobacterium tuberculosis (MTB) infection. However, hookworm infection decreases
      the immune response to hookworm and bystander antigens. Currently, immune
      responses to co-infection of MTB and hookworm are still unknown, although co
      infection has been one of the public health problems in co-endemic areas of
      pulmonary tuberculosis (PTB) and hookworm disease. Therefore, it is essential to
      evaluate B and T cell immune responses to the co-infection. METHODS: Seventeen
      PTB cases co-infected with hookworm, 26 PTB cases, 15 patients with hookworm
      infection, and 24 healthy controls without PTB or hookworm infection were
      enrolled in the study. Expressions of CD3, CD4, CD8, CD10, CD19, CD20, CD21,
      CD25, CD27, CD38, FoxP3, and PD-1 were assessed on B and T cell subsets using
      multicolor flow cytometry. RESULTS: For the B cell (CD19(+)) subsets, naive B
      cells (CD10(-)CD27(-)CD21(+)CD20(+)), plasma cells (CD10(-)CD27(+)CD21(-)CD20(
      )), and tissue-like memory B cells (CD10(-)CD27(-)CD21(-)CD20(+)) had higher
      proportions, whilst resting memory B cells (CD10(-)CD27(+)CD21(+)CD20(+)) had
      lower proportions in the group co-infected with MTB and hookworm as compared to
      other groups. Frequencies of activated memory B cells (CD10(-)CD27(+)CD21(
      )CD20(+)) did not differ among the four groups. For the T cell (CD3(+)) subsets,
      frequencies of regulatory T cells (CD4(+)CD25(+)Foxp3(+)) and exhausted CD4(+)
      and CD8(+) T cells (CD4(+)PD-1(+) and CD8(+)PD-1(+)) were higher, and frequencies
      of activated CD4(+) and CD8(+) T cells (CD4(+)CD38(+) and CD8(+)CD38(+)) were
      lower in the co-infected group as compared to the other groups. CONCLUSION: The
      change patterns of the cell profile of circulating lymphocytes were indentified
      in human co-infection of MTB and hookworm, which might indicate that the humoral
      and cellular immune responses are more suppressed.

PMID- 25954507
TI  - Extent of morbidity associated with schistosomiasis infection in Malawi: a review
      paper.
AB  - Data on the extent of the burden due to schistosomiasis is sparse in most Sub
      Saharan African countries. However, this data is crucial for triggering medical
      attention. A review of extent of morbidity and determinants associated with
      schistosomiasis in Malawi was therefore conducted to quantify the infection in
      order to concretise the need for medical intervention. A systematic and
      traditional search strategy was used to find literature for the review, whilst
      exclusion and inclusion criteria were used to identify appropriate articles.
      Logistic regression curves of epidemiological model Y = (a + bx (c) )/(1 + bx (c)
      ) and the recommendation that schistosomiasis prevalence can be used to estimate
      morbidity were employed to quantify morbidity at various infection stages.
      Morbidity was quantified as a direct proportion of the population and the
      respective national schistosomiasis prevalence. Findings showed that both S.
      mansoni and S. haematobium are present in Malawi with the latter highly prevalent
      (50%). Furthermore, out of the estimated population of 16,829 million,
      approximately 8.4 million have schistosomiasis, with about 4.4 million of these
      aged 18 years and below. The most frequent manifestation is Katayama syndrome,
      while ascites is the lowest, impacting about 3.0 million and 960 individuals,
      respectively. Localised studies on association of schistosomiasis infection to
      risk factors such as occupation, age and gender found odds ratio (OR) ranging
      from 1.29 to 5.37. Morbidity due to schistosomiasis is high in Malawi. It is
      therefore recommended that a more detailed study on the determinants of high
      schistosomiasis and re-evaluation of the current control measures be conducted if
      the current morbidity statistics are to be remarkably reduced. 

PMID- 25954508
TI  - Developing the Pieta House Suicide Intervention Model: a quasi-experimental,
      repeated measures design.
AB  - BACKGROUND: While most crisis intervention models adhere to a generalised
      theoretical framework, the lack of clarity around how these should be enacted has
      resulted in a proliferation of models, most of which have little to no empirical
      support. The primary aim of this research was to propose a suicide intervention
      model that would resolve the client's suicidal crisis by decreasing their
      suicidal ideation and improve their outlook through enhancing a range of
      protective factors. The secondary aim was to assess the impact of this model on
      negative and positive outlook. METHODS: A quasi-experimental, pre-test post-test
      repeated measures design was employed. A questionnaire assessing self-esteem,
      depression, and positive and negative suicidal ideation was administered to the
      same participants pre- and post- therapy facilitating paired responses. RESULTS:
      Multiple analysis of variance and paired-samples t-tests were conducted to
      establish whether therapy using the PH-SIM had a significant effect on the
      clients' negative and positive outlook. Analyses revealed a statistically
      significant effect of therapy for depression, negative suicidal ideation, self
      esteem, and positive suicidal ideation. Negative outlook was significantly lower
      after therapy and positive outlook significantly higher. CONCLUSIONS: The
      decreased negative outlook and increased positive outlook following therapy
      provide some support for the proposed model in fulfilling its role, though
      additional research is required to establish the precise role of the intervention
      model in achieving this.

PMID- 25954509
TI  - Equilibrium and kinetic studies of copper biosorption by dead Ceriporia lacerata
      biomass isolated from the litter of an invasive plant in China.
AB  - BACKGROUND: Ceriporia lacerata, a strain of white-rot fungus isolated from the
      litter of an invasive plant (Solidago canadensis) in China, was little known
      about its properties and utilization. In this work, the copper(II) biosorption
      characteristics of formaldehyde inactivated C. lacerata biomass were examined as
      a function of initial pH, initial copper(II) concentration and contact time, and
      the adsorptive equilibrium and kinetics were simulated, too. RESULTS: The optimum
      pH was found to be 6.0 at experimental conditions of initial copper(II)
      concentration 100 mg/L, biomass dose 2 g/L, contact time 12 h, shaking rate 150
      r/min and temperature 25 degrees C. Biosorption equilibrium cost about 1 hour at
      experimental conditions of pH 6.0, initial copper(II) concentration 100 mg/L, C.
      lacerata dose 2 g/L, shaking rate 150 r/min and temperature 25 degrees C. At
      optimum pH 6.0, highest copper(II) biosorption amounts were 6.79 and 7.76 mg/g
      for initial copper(II) concentration of 100 and 200 mg/L, respectively (with
      other experimental parameters of C. lacerata dose 2 g/L, shaking rate 150 r/min
      and temperature 25 degrees C). The pseudo second-order adsorptive model gave the
      best adjustment for copper(II) biosorption kinetics. The equilibrium data fitted
      very well to both Langmuir and Freundlich adsorptive isotherm models.
      CONCLUSIONS: Without further acid or alkali treatment for improving adsorption
      properties, formaldehyde inactivated C. lacerata biomass possesses good
      biosorption characteristics on copper(II) removal from aqueous solutions.

PMID- 25954510
TI  - Comparison of two different scheimpflug devices in the detection of keratoconus,
      regular astigmatism, and healthy corneas.
AB  - Aim. The aim of this study was to determine the intra- and interobserver
      variability of two Scheimpflug based camera systems, Pentacam and Sirius. In
      addition, the comparability of the measurements was tested in healthy subjects,
      subjects with regular astigmatism, and keratoconus patients. Methods. Intra- and
      interobserver variability were assessed in 20 healthy corneas. Pachymetry values
      were also compared with ultrasound pachymetry as a reference measurement. To
      detect possible differences between the two devices, 82 eyes with clinically
      established keratoconus, 30 eyes with regular astigmatism (>1.5 D), and 60 eyes
      without corneal pathologies were included in this prospective study. Results.
      Pachymetry and keratometry showed good intra- and interobserver variability for
      both devices. Pachymetry values obtained with the Sirius system (579 +/- 58 MUm)
      were significantly higher compared to the Pentacam system (551 +/- 40 MUm, P <
      0.001) and to ultrasound pachymetry (550 +/- 43 MUm, P < 0.001). Significant
      interdevice differences were found regarding the majority of the detected
      keratometry parameters. Conclusions. Both devices show almost perfect
      reproducibility in healthy subjects. However, pachymetry and keratometry values
      of the two devices should not be used interchangeably. 

PMID- 25954511
TI  - Incidence and Outcomes of Anterior Chamber Gas Bubble during Femtosecond Flap
      Creation for Laser-Assisted In Situ Keratomileusis.
AB  - Purpose. To report the incidence and outcomes of anterior chamber gas bubble
      formation during femtosecond laser flap creation for laser-assisted in situ
      keratomileusis (LASIK). Methods. The charts of 2,886 consecutive eyes that
      underwent femtosecond LASIK from May 2011 through August 2014 were
      retrospectively reviewed. The incidence, preoperative characteristics,
      intraoperative details, and postoperative outcomes were analyzed in subjects
      developing anterior chamber gas bubble formation during the procedure. Results. A
      total of 4 cases (0.14%) developed anterior chamber gas bubble formation during
      femtosecond laser flap creation. In all four cases, the excimer laser was unable
      to successfully track the pupil immediately following the anterior chamber bubble
      formation, temporarily postponing the completion of the procedure. There was an
      ethnicity predilection of anterior chamber gas formation toward Asians (p =
      0.0055). An uncorrected visual acuity of 20/20 was ultimately achieved in all
      four cases without further complications. Conclusions. Anterior chamber gas
      bubble formation during femtosecond laser flap creation for LASIK is an uncommon
      event that typically results in a delay in treatment completion; nevertheless, it
      does influence final positive visual outcome. 

PMID- 25954512
TI  - Fusional vergence detected by prism bar and synoptophore in chinese childhood
      intermittent exotropia.
AB  - Purpose. To measure the changes in fusional vergence in Chinese children with
      intermittent exotropia (IXT) and the association with the control of IXT.
      Methods. Ninety-two patients with IXT (8-15 years old) were compared with 86
      controls. Exodeviation control was evaluated using the Revised Newcastle Control
      Score. Angle of deviation was measured using prism and alternate cover testing at
      distance and near. Fusional vergence was measured using prism bar and
      synoptophore. This study was registered with ChiCTR-RCC-13003920. Results. Using
      prism bar, convergence break points were lower whereas divergence break points
      were higher in children with IXT at distance (P < 0.001) and near (P < 0.001)
      compared with controls. There was no significant difference in mean divergence
      amplitudes between the two groups when testing using a synoptophore (P = 0.53).
      In children with IXT, the distance between recovery point and break point in both
      convergence (distance: P = 0.02; near: P = 0.02) and divergence (distance: P <
      0.001; near: P < 0.001) was larger than controls when detected by prism bar and
      synoptophore (convergence: P = 0.005; divergence: P = 0.006). Conclusions.
      Children with IXT have reduced convergence amplitudes as detected by both prism
      bar and synoptophore. 

PMID- 25954514
TI  - Comment on "management of atrial fibrillation in critically ill patients".

PMID- 25954513
TI  - Propofol infusion syndrome in adults: a clinical update.
AB  - Propofol infusion syndrome is a rare but extremely dangerous complication of
      propofol administration. Certain risk factors for the development of propofol
      infusion syndrome are described, such as appropriate propofol doses and durations
      of administration, carbohydrate depletion, severe illness, and concomitant
      administration of catecholamines and glucocorticosteroids. The pathophysiology of
      this condition includes impairment of mitochondrial beta-oxidation of fatty
      acids, disruption of the electron transport chain, and blockage of beta
      adrenoreceptors and cardiac calcium channels. The disease commonly presents as an
      otherwise unexplained high anion gap metabolic acidosis, rhabdomyolysis,
      hyperkalemia, acute kidney injury, elevated liver enzymes, and cardiac
      dysfunction. Management of overt propofol infusion syndrome requires immediate
      discontinuation of propofol infusion and supportive management, including
      hemodialysis, hemodynamic support, and extracorporeal membrane oxygenation in
      refractory cases. However, we must emphasize that given the high mortality of
      propofol infusion syndrome, the best management is prevention. Clinicians should
      consider alternative sedative regimes to prolonged propofol infusions and remain
      within recommended maximal dose limits. 

PMID- 25954515
TI  - Biofeedback Intervention for Stress, Anxiety, and Depression among Graduate
      Students in Public Health Nursing.
AB  - Globally, graduate students have been found to have high prevalence of mental
      health problems. With increasing severity of mental health problems on university
      campuses and limited resources for mental health treatment, alternative
      interventions are needed. This study investigated the use of biofeedback training
      to help reduce symptoms of stress, anxiety, and depression. A sample of 60
      graduate students in public health nursing was randomly assigned to either the
      biofeedback intervention or the control group. Results indicated that biofeedback
      intervention was effective in significantly reducing the levels of stress,
      anxiety, and depression over the 4-week period, while the control group had
      increases in symptoms of anxiety and depression over the same timeframe. As
      future leaders in the public health nursing arena, the more psychologically
      healthy the graduate students in public health nursing are, the better the public
      health nursing professionals they will be as they go forth to serve the community
      after graduation. 

PMID- 25954516
TI  - Nanoparticle enhanced MRI scanning to detect cellular inflammation in
      experimental chronic renal allograft rejection.
AB  - Objectives. We investigated whether ultrasmall paramagnetic particles of iron
      oxide- (USPIO-) enhanced magnetic resonance imaging (MRI) can detect experimental
      chronic allograft damage in a murine renal allograft model. Materials and
      Methods. Two cohorts of mice underwent renal transplantation with either a
      syngeneic isograft or allograft kidney. MRI scanning was performed prior to and
      48 hours after USPIO infusion using T2(*)-weighted protocols. R2(*) values were
      calculated to indicate the degree of USPIO uptake. Native kidneys and skeletal
      muscle were imaged as reference tissues and renal explants analysed by histology
      and electron microscopy. Results. R2(*) values in the allograft group were higher
      compared to the isograft group when indexed to native kidney (median 1.24
      (interquartile range: 1.12 to 1.36) versus 0.96 (0.92 to 1.04), P < 0.01). R2(*)
      values were also higher in the allograft transplant when indexed to skeletal
      muscle (6.24 (5.63 to 13.51)) compared to native kidney (2.91 (1.11 to 6.46) P <
      0.05). Increased R2(*) signal in kidney allograft was associated with macrophage
      and iron staining on histology. USPIO were identified within tissue resident
      macrophages on electron microscopy. Conclusion. USPIO-enhanced MRI identifies
      macrophage. 

PMID- 25954518
TI  - The Discovery of Novel Selective D1 Dopaminergic Agonists: A-68930, A-77636, A
      86929, and ABT-413.
AB  - The novel selective D1 dopaminergic full agonists A-68930, A-77636 were
      discovered by the synthesis of molecules to probe the bioactive conformation of
      the partial agonist SKF-38393, by the use of this information to add D1 affinity
      and selectivity to a screening hit, and by traditional medicinal chemistry
      exploration of structure-activity relationships. The subsequent design of A-86929
      and ABT-413 capitalized on these results, recently disclosed agonists, and
      traditional medicinal chemistry. 

PMID- 25954519
TI  - Pyrazolo derivatives as potent adenosine receptor antagonists: an overview on the
      structure-activity relationships.
AB  - In the past few decades, medicinal chemistry research towards potent and
      selective antagonists of human adenosine receptors (namely, A1, A2A, A2B, and A3)
      has been evolving rapidly. These antagonists are deemed therapeutically
      beneficial in several pathological conditions including neurological and renal
      disorders, cancer, inflammation, and glaucoma. Up to this point, many classes of
      compounds have been successfully synthesized and identified as potent human
      adenosine receptor antagonists. In this paper, an overview of the structure
      activity relationship (SAR) profiles of promising nonxanthine pyrazolo
      derivatives is reported and discussed. We have emphasized the SAR for some
      representative structures such as pyrazolo-[4,3-e]-1,2,4-triazolo-[1,5
      c]pyrimidines; pyrazolo-[3,4-c] or -[4,3-c]quinolines; pyrazolo-[4,3
      d]pyrimidinones; pyrazolo-[3,4-d]pyrimidines and pyrazolo-[1,5-a]pyridines. This
      overview not only clarifies the structural requirements deemed essential for
      affinity towards individual adenosine receptor subtypes, but it also sheds light
      on the rational design and optimization of existing structural templates to allow
      us to conceive new, more potent adenosine receptor antagonists. 

PMID- 25954520
TI  - Pharmacophore modelling and synthesis of quinoline-3-carbohydrazide as
      antioxidants.
AB  - From well-known antioxidants agents, we developed a first pharmacophore model
      containing four common chemical features: one aromatic ring and three hydrogen
      bond acceptors. This model served as a template in virtual screening of Maybridge
      and NCI databases that resulted in selection of sixteen compounds. The selected
      compounds showed a good antioxidant activity measured by three chemical tests:
      DPPH radical, OH degrees  radical, and superoxide radical scavenging. New
      synthetic compounds with a good correlation with the model were prepared, and
      some of them presented a good antioxidant activity. 

PMID- 25954517
TI  - Dopamine receptors and Parkinson's disease.
AB  - Parkinson's disease (PD) is a progressive extrapyramidal motor disorder.
      Pathologically, this disease is characterized by the selective dopaminergic
      (DAergic) neuronal degeneration in the substantia nigra. Correcting the DA
      deficiency in PD with levodopa (L-dopa) significantly attenuates the motor
      symptoms; however, its effectiveness often declines, and L-dopa-related adverse
      effects emerge after long-term treatment. Nowadays, DA receptor agonists are
      useful medication even regarded as first choice to delay the starting of L-dopa
      therapy. In advanced stage of PD, they are also used as adjunct therapy together
      with L-dopa. DA receptor agonists act by stimulation of presynaptic and
      postsynaptic DA receptors. Despite the usefulness, they could be causative drugs
      for valvulopathy and nonmotor complication such as DA dysregulation syndrome
      (DDS). In this paper, physiological characteristics of DA receptor familyare
      discussed. We also discuss the validity, benefits, and specific adverse effects
      of pharmaceutical DA receptor agonist. 

PMID- 25954521
TI  - Differential Effect of the Dopamine D3 Agonist (+/-)-7-Hydroxy-2-(N,N-di-n
      propylamino) Tetralin (7-OH-DPAT) on Motor Activity between Adult Wistar and
      Sprague-Dawley Rats after a Neonatal Ventral Hippocampus Lesion.
AB  - The neonatal ventral hippocampal lesion (nVHL) has been widely used as an animal
      model for schizophrenia. Rats with an nVHL show several delayed behavioral
      alterations that mimic some symptoms of schizophrenia. Sprague-Dawley (SD) rats
      with an nVHL have a decrease in D3 receptors in limbic areas, but the expression
      of D3 receptors in Wistar (W) rats with an nVHL is unknown. The 7-Hydroxy-2-(N,N
      di-n-propylamino) tetralin (7-OH-DPAT) has been reported as a D3-preferring
      agonist. Thus, we investigated the effect of (+/-)-7-OH-DPAT (0.25 mg/kg) on the
      motor activity in male adult W and SD rats after an nVHL. The 7-OH-DPAT caused a
      decrease in locomotion of W rats with an nVHL, but it did not change the
      locomotion of SD rats with this lesion. Our results suggest that the differential
      effect of 7-OH-DPAT between W and SD rats with an nVHL could be caused by a
      different expression of the D3 receptors. These results may have implications for
      modeling interactions of genetic and environmental factors involved in
      schizophrenia. 

PMID- 25954522
TI  - Design, Synthesis, and Antifungal Activity of New alpha-Aminophosphonates.
AB  - alpha-Aminophosphonates are bioisosteres of amino acids and have several
      pharmacological activities. These compounds have been synthesized by various
      routes from reaction between amine, aldehyde, and phosphite compounds. In order
      to synthesize alpha-aminophosphonates, catalytic effect of CuCl2 was compared
      with FeCl3. Also all designed structures as well as griseofulvin were docked into
      the active site of microtubule (1JFF), using Autodock program. The results showed
      that the reactions were carried out in the presence of CuCl2 in lower yields, and
      also the time of reaction was longer in comparison with FeCl3. The chemical
      structures of the new compounds were confirmed by spectral analyses. The
      compounds were investigated for antifungal activity against several fungi in
      comparison with griseofulvin. An indole-derived bis(alpha-aminophosphonates) with
      the best negative DeltaG in docking study showed maximum antifungal activity
      against Microsporum canis, and other investigated compounds did not have a good
      antifungal activity. 

PMID- 25954523
TI  - Synthesis of the nakanishi ring-locked retinoid.
AB  - An optimized synthetic route to prepare ring-locked retinoid 1a has been
      developed. We fully describe a purification protocol that provides isomerically
      pure 1a in support of on-going proof of concept studies for the development of
      therapeutic agents to treat human ADRP. Additionally, we have found that
      isomerically pure 1a can be stored in amber vials under argon at -20 degrees C
      for use over time (up to six months) without degradation. Thus, enabling 1a to be
      an accessible and valuable biological tool. 

PMID- 25954524
TI  - Current updates on oxazolidinone and its significance.
AB  - Oxazolidinone is a five-member heterocyclic ring exhibiting potential medicinal
      properties with preferential antibacterial activity. Scientists reported various
      synthetic procedures for this heterocyclic structure. Current review articles
      tried to cover each and every potential aspect of oxazolidinone like synthetic
      routes, pharmacological mechanism of action, medicinal properties, and current
      research activities. 

PMID- 25954525
TI  - Development of 5-Substituted N-Methylmorphinan-6-ones as Potent Opioid Analgesics
      with Improved Side-Effect Profile.
AB  - One of the most important functions of the opioid system is the control of pain.
      Among the three main opioid receptor classes (MU, delta, kappa), the MU (MOR) is
      the main type targeted for pharmacotherapy of pain. Opioid analgesics such as
      morphine, oxycodone and fentanyl are agonists at the MOR and are the mainstay for
      the treatment of moderate-to-severe pain. However, adverse effects related to
      opioid use are severe and often lead to early discontinuation and inadequate
      analgesia. The development of more effective and safer medications for the
      management of pain still remains a major direction in pharmaceutical research.
      Chemical approaches towards the identification of novel MOR analgesics with
      reduced side effects include structural modifications of 14-alkoxy-N
      methylmorphinan-6-ones in key positions that are important for binding,
      selectivity, potency, and efficacy at opioid receptors. This paper describes a
      representative strategy to improve the therapeutic usefulness of opioid
      analgesics from the morphinan class of drugs by targeting position 5. The focus
      is on chemical and biological studies and structure-activity relationships of
      this series of ligands. We report on 14-alkoxymorphinan-6-ones having a methyl
      and benzyl group at position 5 as strong opioid antinociceptive agents with
      reduced propensity to cause undesired effects compared to morphine although
      interacting selectively with MORs. 

PMID- 25954527
TI  - Identification of a Novel Series of Potent TrkA Receptor Tyrosine Kinase
      Inhibitors.
AB  - A novel series of N-(3-(6-substituted-aminopyridin-3-yloxy)phenyl)-2-oxo-3
      phenylimidazolidine-1-carboxamides targeting TrkA receptor tyrosine kinase was
      identified. SAR study of the series allowed us to design and synthesize compounds
      possessing inhibitory activity of TrkA kinase enzyme in the low nanomolar range
      with low residual activity against c-Met and with no significant activity against
      VEGFR2. 

PMID- 25954526
TI  - MDAN-21: A Bivalent Opioid Ligand Containing mu-Agonist and Delta-Antagonist
      Pharmacophores and Its Effects in Rhesus Monkeys.
AB  - MDAN-21, 7'-{2-[(7-{2-[({(5alpha, 6alpha)-4,5-Epoxy-3,14-dihydroxy-17
      methylmorphin-6-yl}-aminocarbonyl)metoxy]-acetylamino}-heptylaminocarbonyl)
      methoxy]-acetylamino}-naltrindole, a bivalent opioid ligand containing a mu
      opioid receptor agonist (derived from oxymorphone) linked to the delta-opioid
      receptor antagonist (related to naltrindole) by a spacer of 21 atoms, was
      reported to have potent analgesic properties in mice. Tolerance, physical
      dependence, and conditioned place preference were not evident in that species.
      The finding that bivalent ligands in this series, with spacers 19 atoms or
      greater, were devoid of tolerance and dependence led to the proposal that MDAN-21
      targets heteromeric mu-delta-opioid receptors. The present study focused on its
      effects in nonhuman primates (Macaca mulatta), a species with a physiology and
      behavioral repertoire not unlike humans. With regard to opioids, this species
      usually better predicts clinical outcomes. MDAN-21 substituted for morphine in
      morphine-dependent monkeys in the remarkably low dose range 0.006-0.032 mg/kg,
      subcutaneously. Although MDAN-21 failed to produce reliable thermal analgesia in
      the dose range 0.0032-0.032 mg/kg, intramuscularly, it was active in the same
      dose range and by the same route of administration, in the capsaicin-induced
      thermal allodynia assay. The results suggest that MDAN-21 may be useful in the
      treatment of opioid dependence and allodynia. The data provide additional
      evidence that opioid withdrawal is associated with sensitized pain. 

PMID- 25954529
TI  - The Fate of Sulfamethazine in Sodium-Hypochlorite-Treated Drinking Water:
      Monitoring by LC-MS (n) -IT-TOF.
AB  - Pharmaceutical compounds represent a rapidly emerging class of environmental
      contaminants. Such compounds were recently classified by the U.S. Geological
      Survey, including several antibiotics. An LC-MS/MS screening method for the top
      five antibiotics in drinking water was developed and validated using a Shimadzu
      LC-MS-IT-TOF. The separation was performed using a Waters Acquity UPLC BEH C18
      column with a gradient elution. Sulfamethazine was exposed to conditions intended
      to mimic drinking water chlorination, and samples were collected and quenched
      with excess sodium sulfite. Kinetics of sulfamethazine degradation was followed
      as well as the formation of the major chlorinated byproduct (m/z 313). For the
      screening method, all five antibiotic peaks were baseline resolved within 5
      minutes. Additionally, precision and accuracy of the screening method were less
      than 15%. Degradation of sulfamethazine upon exposure to drinking water
      chlorination occurred by first order kinetics with a half-life of 5.3 * 10(4) min
      (approximately 37 days) with measurements starting 5 minutes after chlorination.
      Likewise, the formation of the major chlorinated product occurred by first order
      kinetics with a rate constant of 2.0 * 10(-2). The proposed identification of the
      chlorinated product was 4-amino-(5-chloro-4,6-dimethyl-2-pyrimidinyl)
      benzenesulfonamide (C12H13N4O2SCl) using MS (n) spectra and databases searches of
      SciFinder and ChemSpider. 

PMID- 25954528
TI  - 2',6'-dimethylphenylalanine: a useful aromatic amino Acid surrogate for tyr or
      phe residue in opioid peptides.
AB  - Two aromatic amino acids, Tyr(1) and Phe(3) or Phe(4), are important structural
      elements in opioid peptides because they interact with opioid receptors. The
      usefulness of an artificial amino acid residue 2',6'-dimethylphenylalanine (Dmp)
      was investigated as an aromatic amino acid surrogate for several opioid peptides,
      including enkephalin, dermorphin, deltorphin, endomorphin, dynorphin A, and
      nociceptin peptides. In most peptides, substitutions of Phe(3) by a Dmp residue
      produced analogs with improved receptor-binding affinity and selectivity, while
      the same substitution of Phe(4) induced markedly reduced receptor affinity and
      selectivity. Interestingly, replacement of Tyr(1) by Dmp produced analogs with
      unexpectedly high affinity or produced only a slight drop in receptor affinity
      and bioactivity for most peptides. Thus, Dmp is also a useful surrogate for the N
      terminal Tyr residue in opioid peptides despite the lack of a phenolic hydroxyl
      group, which is considered necessary for opioid activity. The Dmp(1)-substituted
      analogs are superior to 2',6'-dimethyltyrosine (Dmt)(1)-substituted analogs for
      high receptor selectivity since the latter generally have poor receptor
      selectivity. Thus, Dmp is very useful as an aromatic amino acid surrogate in
      opioid peptides and may be useful for developing other novel peptide mimetics
      with high receptor specificity. 

PMID- 25954530
TI  - Developmental potential for endomorphin opioidmimetic drugs.
AB  - Morphine, which is agonist for MU-opioid receptors, has been used as an anti-pain
      drug for millennia. The opiate antagonists, naloxone and naltrexone, derived from
      morphine, were employed for drug addiction and alcohol abuse. However, these
      exogenous agonists and antagonists exhibit numerous and unacceptable side
      effects. Of the endogenous opioid peptides, endomorphin(EM)-1 and endomorphin(EM)
      2 with their high MU-receptor affinity and exceptionally high selectivity
      relative to delta- and kappa-receptors in vitro and in vivo provided a
      sufficiently sequence-flexible entity in order to prepare opioid-based drugs. We
      took advantage of this unique feature of the endomorphins by exchanging the N
      terminal residue Tyr(1) with 2',6'-dimethyl-l-tyrosine (Dmt) to increase their
      stability and the spectrum of bioactivity. We systematically altered specific
      residues of [Dmt(1)]EM-1 and [Dmt(1)]EM-2 to produce various analogues. Of these
      analogues, [N-allyl-Dmt(1)]EM-1 (47) and [N-allyl-Dmt(1)]EM-2 (48) exhibited
      potent and selective antagonism to MU-receptors: they completely inhibited
      naloxone- and naltrexone-induced withdrawal from following acute morphine
      dependency in mice and reversed the alcohol-induced changes observed in sIPSC in
      hippocampal slices. Overall, we developed novel and efficacious opioid drugs
      without deleterious side effects that were able to resist enzymatic degradation
      and were readily transported intact through epithelial membranes in the
      gastrointestinal tract and the blood-brain-barrier. 

PMID- 25954531
TI  - Synthesis and biological evaluation of achiral indole-substituted titanocene
      dichloride derivatives.
AB  - Six new titanocene compounds have been isolated and characterised. These
      compounds were synthesised from their fulvene precursors using Super Hydride
      (LiBEt3H) followed by transmetallation with titanium tetrachloride to yield the
      corresponding titanocene dichloride derivatives. These complexes are bis-[((1
      methyl-3-diethylaminomethyl)indol-2-yl)methylcyclopentadienyl] titanium (IV)
      dichloride (5a), bis-[((5-methoxy-1-methyl,3-diethylaminomethyl)indol-2
      yl)methylcyclopentadienyl] titanium (IV) dichloride (5b), bis-[((1-methyl,3
      diethylaminomethyl)indol-4-yl)methylcyclopentadienyl] titanium (IV) dichloride
      (5c), bis-[((5-bromo-1-methyl)indol-3-yl)methylcyclopentadienyl] titanium (IV)
      dichloride (5d), bis-[((5-chloro-1-methyl)indol-3-yl)methylcyclopentadienyl]
      titanium (IV) dichloride (5e), and bis-[((5-fluoro-1-methyl)indol-3
      yl)methylcyclopentadienyl] titanium (IV) dichloride (5f). All six titanocenes 5a
      5f were tested for their cytotoxicity through MTT-based in vitro tests on CAKI-1
      cell lines using DMSO and Soluphor P as solubilising agents in order to determine
      their IC50 values. Titanocenes 5a-5f were found to have IC50 values of 10 (+/-2),
      21 (+/-3), 29 (+/-4), 140 (+/-6), and 450 (+/-10) MUM when tested using DMSO. 

PMID- 25954532
TI  - A comparison of the efficacy and cost of different venous leg ulcer dressings: a
      retrospective cohort study.
AB  - Objective. To compare the efficacy and cost-effectiveness of simple nonadherent
      dressings with other more expensive dressing types in the treatment of venous leg
      ulcers. Study Design. Retrospective cohort study. Location. The leg ulcer clinic
      at the University Hospital of South Manchester. Subjects and Methods. The healing
      rates of twelve leg ulcer patients treated with simple nonadherent dressings
      (e.g., NA Ultra) were compared with an equal number of patients treated with
      modern dressings to determine differences in healing rates and cost. Main Outcome
      Measures. Rate of healing as determined by reduction in ulcer area over a
      specified period of time and total cost of dressing per patient. Results. Simple
      nonadherent dressings had a mean healing rate of 0.353 cm(2)/week (standard
      deviation +/- 0.319) compared with a mean of 0.415 cm(2)/week (standard deviation
      +/- 0.383) for more expensive dressings. This resulted in a one-tailed p value of
      0.251 and a two-tailed p value of 0.508. Multiple regression analysis gave a
      significance F of 0.8134. Conclusion. The results indicate that the difference in
      healing rate between simple and modern dressings is not statistically
      significant. Therefore, the cost of dressing type should be an important factor
      influencing dressing selection. 

PMID- 25954534
TI  - A Silent Alarm at Occupational Evaluation Two Months after a Normal Painful ECG:
      A Case of Wellens' syndrome.
AB  - We describe a case of a 42-year-old man, with a previous episode of angina and a
      normal ECG and serum cardiac markers, and a two months later finding of biphasic
      T wave in leads V2-V3 and deeply inverted T wave in V4-V5 at a asymptomatic
      occupational evaluation. This is a typical ECG pattern of Wellens' syndrome. A
      subsequent coronary angiography showed a critical stenosis of proximal left
      anterior descendent. We underline the careful value of prolonged observation in
      chest pain unit and repetitive ECG evaluation also during pain-free period after
      an angina episode, to exclude an earlier T wave pseudonormalization. 

PMID- 25954533
TI  - The Relationship between Anterior Cruciate Ligament Injury and Osteoarthritis of
      the Knee.
AB  - Anterior cruciate ligament (ACL) tears are a common injury, particularly in the
      athletic and youth populations. The known association between ACL injury and
      subsequent osteoarthritis (OA) of the knee merits a more in-depth understanding
      of the relationship between the ACL-injured knee and osteoarthritis. ACL injury,
      especially with concomitant meniscal or other ligamentous pathology, predisposes
      the knee to an increased risk of osteoarthritis. ACL insufficiency results in
      deterioration of the normal physiologic knee bending culminating in increased
      anterior tibial translation and increased internal tibial rotation. This leads to
      increased mean contact stresses in the posterior medial and lateral compartments
      under anterior and rotational loading. However, surgical reconstruction of the
      ACL has not been shown to reduce the risk of future OA development back to
      baseline and has variability based on operative factors of graft choice, timing
      of surgery, presence of meniscal and chondral abnormalities, and surgical
      technique. Known strategies to prevent OA development are applicable to patients
      with ACL deficiency or after ACL reconstruction and include weight management,
      avoidance of excessive musculoskeletal loading, and strength training.
      Reconstruction of the ACL does not necessarily prevent osteoarthritis in many of
      these patients and may depend on several external variables. 

PMID- 25954535
TI  - Aesthetic Depigmentation of Gingival Smoker's Melanosis Using Carbon Dioxide
      Lasers.
AB  - Melanic pigmentation results from melanin produced by the melanocytes present in
      the basal layer of the oral epithelium. One of the most common causes of oral
      pigmentation is smoker melanosis, a condition associated with the melanocyte
      stimulation caused by cigarette smoke. This paper aims to illustrate the use of a
      carbon dioxide laser in the removal of the gingival melanic pigmentation for
      aesthetic reasons in a 27-year-old female patient with history of a smoking
      habit. The carbon dioxide laser vaporisation was performed on the gingival mucosa
      with effective and quick results and without any complications or significant
      symptoms after the treatment. We conclude that a carbon dioxide laser could be a
      useful, effective, and safe instrument to treat the aesthetic complications
      caused by oral smoker melanosis. 

PMID- 25954536
TI  - Rhabdomyolysis and acute renal failure after gardening.
AB  - Acute nontraumatic exertional rhabdomyolysis may arise when the energy supply to
      muscle is insufficient to meet demands, particularly in physically untrained
      individuals. We report on a psychiatric patient who developed large bruises and
      hemorrhagic blisters on both hands and arms, rhabdomyolysis of both forearm
      muscles with a moderate compartment syndrome, and consecutive acute renal failure
      following excessive work in the garden. Although specifically asked, the patient
      denied any hard physical work or gardening, and heteroanamnestic data were not
      available. The diagnosis of rhabdomyolysis was easy to establish, but until
      reliable anamnestic data were obtained, the etiology remained uncertain. Four
      days after arrival, the patient recalled working hard in the garden. The etiology
      of rhabdomyolysis was finally reached, and the importance of anamnestic data was
      once more confirmed. 

PMID- 25954537
TI  - Acute liver injury with severe coagulopathy in marasmus caused by a somatic
      delusional disorder.
AB  - Marasmus is a severe form of protein-calorie malnutrition characterized by the
      depletion of fat stores, muscle wasting, and the lack of edema. In developed
      countries, marasmus is often the result of anorexia nervosa. Abnormal
      transaminases with liver synthetic dysfunction have rarely been reported with
      anorexia nervosa. To our knowledge, we report the first detailed case of acute
      liver injury with severe coagulopathy (INR > 1.5) in a patient with marasmus due
      to self-induced calorie restriction caused by a somatic delusional disorder. This
      case highlights the severity of liver injury that may occur with significant
      weight loss from self-induced calorie restriction and the rapid normalization of
      this injury with treatment. It is important for clinicians to be aware of
      patterns of acute liver injury in patients with severe protein-calorie
      malnutrition, regardless of the underlying cause. 

PMID- 25954538
TI  - Hepatitis B Reactivation in a HBsAg-Negative, HBcAb-Positive Patient Receiving
      Fludarabine for the Treatment of Chronic Lymphocytic Leukaemia.
AB  - Hepatitis B virus (HBV) reactivation is an increasingly recognized cause of
      morbidity and mortality in patients undergoing chemotherapy. In haematology, the
      risk of reactivation of B hepatitis among HBsAg-positive patients has been
      documented; therefore, use of lamivudine prophylaxis is recommended before
      starting chemotherapy. Differently, for HBsAg-negative patients with markers of
      previous HBV infection (i.e., presence of isolated anti-HBc positivity) (anticore
      patients) management strategies are not univocal. We describe a rare case of HBV
      reactivation in an anticore patient after fludarabine therapy for chronic
      lymphocytic leukaemia. The patient fully recovered after a 6-month course of
      lamivudine with persistent HBV-DNA clearance and loss of HBsAg. The most
      important feature of this case is that fludarabine alone infrequently determines
      HBV reactivation, especially in anticore patients. Therefore, we suggest that
      patients candidates to receive fludarabine therapy should be considered for
      lamivudine prophylaxis, not only if HBsAg-positive, but even if anticore-positive
      only. 

PMID- 25954539
TI  - Uptake of (18) FDG by a Hepatic Adenoma on Positron Emission Tomography.
AB  - Fluorodeoxyglucose positron emission tomography ((18)FDG-PET) is currently the
      best noninvasive test to confirm hepatic metastases when diagnostic uncertainty
      exists after initial imaging with first-line modalities. However, we report the
      second case of "false-positive" uptake of (18)FDG on PET scanning from a
      histopathologically confirmed hepatic adenoma. 

PMID- 25954541
TI  - Hemothorax an Unusual Complication during Liver RFA.
AB  - We present a case of a 70-year-old patient with hepatocellular carcinoma treated
      with RFA. The lesion was located in segment II under the ribs. During RFA pleural
      effusion is presented. After the procedure a dual phase CT revealed haemothorax
      and extravasation of the contrast medium from the intercostal vessels. 

PMID- 25954540
TI  - A case of prolonged cholestatic hepatitis induced by azithromycin in a young
      woman.
AB  - Azithromycin, a semisynthetic macrolides, is frequently prescribed for the
      treatment of middle ear and upper respiratory tract infections, bronchitis, and
      community-acquired pneumonia. This antibiotic is usually well tolerated, and a
      rapid resolving cholestatic hepatitis has been described up to now only in six
      patients all, except one, over 65 years of age. We here report the case of a
      prolonged cholestatic hepatitis after administration of azithromycin in a young
      woman with no history of liver disease. 

PMID- 25954542
TI  - Diagnostic challenge of hepatopulmonary syndrome in a patient with coexisting
      structural heart disease.
AB  - Hepatopulmonary syndrome (HPS) is a severe complication seen in advance liver
      disease. Its prevalence among cirrhotic patients varies from 4-47 percent. HPS
      exact pathogenesis remains unknown. Patient presents with signs/symptoms of
      chronic liver disease, and dypsnea of variable severity. Our patient is a 62
      years old white male with a known history of chronic hepatitis C, cirrhosis,
      ascites, and hypothyroidism who presented to GI/liver clinic complaining of 1
      episode BRBPR, and exacerbating dypsnea associated with nausea and few episodes
      of non-bloody vomit. Physical exam showed, icterus, jaundice, few small spider
      angiomas on the chest, decrease breath sounds bilateral right more than left, and
      mild tachycardic. Abdominal exam revealed mid-line scar, moderated size ventral
      hernia, distention, diffused tenderness, and dullness to percussion. Laboratory
      result: CBC 5.2/13.2/37.6/83, LFTs 83/217/125/5.2/4.7/7.4, Pt 22.6 INR 1.9
      PTT35.4. CT scan showed liver cirrhosis, abdominal varices, and moderated ascites
      collection around ventral hernia. Calculated A-a gradient was 49.5.
      Echocardiography revealed patent foramen ovale (PFO) with predominant left to
      right shunt. In our case, existence of paten foramen ovale (PFO) and atelectasis
      precludes definitive diagnosis of HPS. Presence of cardiopulmonary shunt could be
      partially responsible for the patient's dypsnea exacerbation. 

PMID- 25954543
TI  - A case of montelukast-induced churg-strauss syndrome associated with liver
      dysfunction.
AB  - A 64-year-old woman was admitted to hospital due to protracted diarrhea and liver
      dysfunction. The patient was diagnosed as Churg-Strauss syndrome (CSS) due to
      asthma, paranasal sinusitis, hypereosinophilia, and polyneuropathy. There was a
      history of taking montelukast, a leukotriene receptor antagonist (LTRA), which is
      thought to have some relationship with CSS. The liver biopsy specimen showed
      eosinophilic infiltration and centrolobular fatty change. In this paper, we
      review the relationship between LTRA and CSS. Several lines of evidence suggest
      that leukotriene plays an important role in maintaining neural tissues. We also
      review the potential relationship between centrolobular fatty change and pivoxil
      containing antibiotics, which was prescribed for sinusitis before admission.
      Carnitine deficiency induced by pivoxil-containing agents may cause impaired
      fatty acid oxidation in mitochondria. 

PMID- 25954544
TI  - Propionibacterium acnes Pyogenic Liver Abscess and Pylephlebitis.
AB  - Reported is an unusual case of pyogenic liver abscess and septic thrombophlebitis
      of the portal vein in a 44-year-old male caused by Propionibacterium acnes
      successfully managed with a combination of percutaneous drainage and
      antimicrobial therapy. To the best of our knowledge, this is the first report of
      this bacterium isolated in pure culture as the sole etiologic organism of
      pyogenic liver abscess and pylephlebitis in an adult patient. 

PMID- 25954545
TI  - Early experience of helical tomotherapy for hepatobiliary radiotherapy.
AB  - Helical tomotherapy (HT), an image-guided, intensity-modulated, radiation therapy
      technique, allows for precise targeting while sparing normal tissues. We
      retrospectively assessed the feasibility and tolerance of the hepatobiliary HT in
      9 patients. A total dose of 54 to 60 Gy was prescribed (1.8 or 2 Gy per fraction)
      with concurrent capecitabine for 7 patients. There were 1 hepatocarcinoma, 3
      cholangiocarcinoma, 4 liver metastatic patients, and 1 pancreatic adenocarcinoma.
      All but one patient received previous therapies (chemotherapy, liver
      radiofrequency, and/or surgery). The median doses delivered to the normal liver
      and to the right kidney were 15.7 Gy and 4.4 Gy, respectively, below the
      recommended limits for all patients. Most of the treatment-related adverse events
      were transient and mild in severity. With a median followup of 12 months, no
      significant late toxicity was noted. Our results suggested that HT could be
      safely incorporated into the multidisciplinary treatment of hepatobiliary or
      pancreatic malignant disease. 

PMID- 25954546
TI  - Acute liver failure secondary to metastatic medullary thyroid cancer.
AB  - Acute liver failure (ALF) is a rare presentation of liver metastases. Although
      cases of ALF from metastatic disease have been reported, etiologies have been
      largely confined to lymphoma, metastatic breast, lung, and gastric cancers. ALF
      from medullary thyroid cancer (MTC) has never been reported. We present a 59-year
      old male with newly diagnosed MTC, who was admitted with ALF. He presented with
      jaundice, hepatic encephalopathy, and synthetic dysfunction. His clinical course
      was marked by rapid decompensation within 6 days from initial presentation of
      jaundice to development of hepatic coma. Although liver metastases from medullary
      thyroid cancer have been reported, to our knowledge, this is the first described
      case of MTC resulting in acute liver failure. 

PMID- 25954547
TI  - Solitary necrotic nodule of the liver: a report of two cases and review of the
      literature.
AB  - To investigate the clinicopathological characteristics and possible causes of
      solitary necrotic nodule of the liver (SNN), two cases of SNN of the liver were
      studied with clinicopathological data, immunohistochemistry, and histochemistry
      staining. The patients had no specific symptoms, with negative results for the
      serum tumor markers. CT and ultrasound all showed low-density lesion.
      Morphologically, there was isolate, single necrosis tubercle of the liver. It was
      composed of a central necrotic core and a peripheral fibrotic capsule with
      inflammatory cells, including histiocytes, plasma cells, lymphocytes, and so
      forth. The staining result of PAS, acid-fast, and iron was all negative, and AG +
      VG staining showed that the outline of reticular fibers and collagen was intact.
      Vimtin was positive for necrotic tissue and surrounding fibrous tissue. CD34 and
      CD68 was both positive for case 1. CK was negative in case 2 but positive for a
      few residual cells in case 1. SNN of the liver is a rare nonmalignant disease
      with a good prognosis. Hemangioma and fatty liver might be ones of the causes of
      SNN. 

PMID- 25954548
TI  - Amanita bisporigera-Induced Hepatic Failure: A Fatal Case of Mushroom Ingestion.
AB  - Wild mushroom poisoning from the genus Amanita is a medical emergency, with
      Amanita phalloides being the most common offender. Patients may complain of
      nausea, vomiting, diarrhea and/or abdominal pain. If not aggressively treated,
      fulminant hepatic failure may develop within several days of ingestion. In this
      case report, a patient poisoned with Amanita bisporigera is described, along with
      the typical clinical presentation, patient outcomes, and treatment options for
      dealing with an Amanita mushroom poisoning. 

PMID- 25954549
TI  - Sorafenib-induced liver failure: a case report and review of the literature.
AB  - In patients with hepatocellular carcinoma characterized by vascular invasion
      and/or extrahepatic disease, Sorafenib is considered treatment of choice.
      Although mild liver test abnormalities were reported in less than 1% of the
      patients in the two large randomized, controlled phase III trials, four cases of
      severe acute Sorafenib-induced hepatitis have been described. One of these four
      cases died from liver failure. In this paper, a patient with HCC with lung
      metastases developed high fever and a severe hepatitis that rapidly evolved into
      liver coma and death, two weeks after the initiation of Sorafenib. Biochemical
      parameters pointed to a hepatocellular type of injury. Clinical and biochemical
      presentations were compatible with a drug-induced hypersensitivity syndrome such
      as it has mainly been described for aromatic anticonvulsants, sulphonamides, and
      allopurinol. We hypothesize that an underlying cytochrome P450 dysfunction with
      the presence of reactive drug metabolites might lead to this potentially fatal
      Sorafenib-induced severe liver dysfunction. 

PMID- 25954550
TI  - Acute Hepatitis Induced by Lyprinol, the Lipid Extract of the Green-Lipped Mussel
      (Perna canaliculus), in a Patient with Polyarthrosis.
AB  - Lyprinol, the lipid extract of the green-lipped mussel (Perna canaliculus), is a
      readily and freely available agent with a putative anti-inflammatory impact. It
      has already found application as a complementary and supplementary treatment of
      osteoarthritis, rheumatoid arthritis, asthma, and cancer. So far no major side
      effects for Lyprinol have been reported, yet. Here, we present the case of a 76
      year-old woman with acutely exacerbating abdominal pain and highly elevated liver
      transaminases while taking Lyprinol as a complementary treatment of
      polyarthrosis. 

PMID- 25954551
TI  - Reversal of jaundice in two patients with inoperable cholangiocarcinoma treated
      with Cisplatin and gemcitabine combination.
AB  - Two patients are presented with severe jaundice, due to inoperable
      cholangiocarcinoma. The chemotherapeutic approach in patients with severe
      jaundice is discussed. Many schedules of chemotherapy were developed in this
      tumor type with normal serum bilirubin. We report here the first successful use
      of cisplatin and gemcitabine combination chemotherapy in these patients.
      Tolerability was good and liver function tests gradually improved. 

PMID- 25954552
TI  - An IgG4-Related Salivary Gland Disorder: A Case Series Presenting with a
      Different Clinical Setting.
AB  - Kuttner tumor is a chronic inflammatory disease that presents with a firm
      swelling of the submandibular gland and often mimics a neoplasm. Recently
      evidence suggests that Kuttner tumor may be a type of disorder characterized by
      IgG4-related inflammations. Herein, we report 3 cases of submandibular gland
      swellings with severe fibrosis, inflammation with marked lymphoplasmacytic
      infiltration; this pathology mimics clinical manifestation of a malignant tumor
      in 18-fluorodeoxyglucose positron emission tomography (FDG-PET) findings. 

PMID- 25954553
TI  - Chylous ascites and pleural transudate: rare presentations in systemic lupus
      erythematosus in old age.
AB  - Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder with
      involvement of multiple organs. Various forms of serositis, including pleural
      effusion, pericardial effusion, and ascites, may be found during the course of
      SLE. Peritoneal involvement by ascites is common in the initial presentation of
      SLE. However, chylous ascites is uncommon in SLE patients. Here, we describe a 93
      year-old female with initial presentation of chylous ascites during SLE flares.
      Marked distention and an ovoid shape of the abdomen were observed. Shifting
      dullness and central tympanic sounds were found on percussion. Rales were heard
      in bilateral breathing sounds, multiple oral ulcers appeared in the oral cavity,
      and chest images showed bilateral pleural effusion. Abdominal sonography revealed
      moderate ascites and pleural effusion. Neither organisms nor malignant cells were
      revealed in the culture or cytology of ascites and pleural effusion. The
      diagnosis of SLE was arrived at by positive antinuclear antibody (ANA), discoid
      rash, oral ulcers, serositis (pleural effusion and ascites), and proteinuria. The
      patient received intravenous methylprednisolone 250 mg/day for three days. The
      pleural effusion resolved dramatically after steroid therapy and abdominal
      distention related to ascites formation subsided obviously. 

PMID- 25954554
TI  - Multiple thromboses in a patient with systemic lupus erythematosus after
      splenectomy.
AB  - Antiphospholipid syndrome is a disorder presenting with arterial or venous
      thrombus and a history of fetal loss. Early diagnosis and adequate treatment is
      important to prevent multiple organ failures. Here, we described a woman with a
      two-year history of systemic lupus erythematosus with severe nephrotic syndrome,
      manifested multiple thrombi over the portal vein and the inferior vena cava,
      combined with acute renal infarction. The patient underwent splenectomy 10 months
      ago. Initially, she received anticoagulant treatment and low-dose glucocorticoid,
      but multiple organ failure progressed. After emergency plasma exchange followed
      by glucocorticoid pulse therapy, the patient recovered. 

PMID- 25954555
TI  - Atypical Omenn Syndrome due to Adenosine Deaminase Deficiency.
AB  - We present here a novel case of an atypical Omenn syndrome (OS) phenotype due to
      mutations in the ADA gene encoding adenosine deaminase. This case is noteworthy
      for a significant increase in circulating CD56(bright)CD16- cytokine-producing NK
      cells after treatment with steroids for skin rash. 

PMID- 25954556
TI  - Cephazolin-induced toxic epidermal necrolysis treated with intravenous
      immunoglobulin and N-acetylcysteine.
AB  - Toxic epidermal necrolysis is the most severe form of drug-induced skin reaction
      and includes denudation of >30% of total body surface area. The mechanism of
      disease is not completely understood, but immunologic mechanisms, cytotoxic
      reactions, and delayed hypersensitivity seem to be involved. We report a case of
      cephazolin-induced toxic epidermal necrolysis treated with intravenous
      immunoglobulin and N-acetylcysteine with excellent response. 

PMID- 25954557
TI  - Allergen Immunotherapy in an HIV+ Patient with Allergic Fungal Rhinosinusitis.
AB  - Patients with HIV/AIDS can present with multiple types of fungal rhinosinusitis,
      fungal balls, granulomatous invasive fungal rhinosinusitis, acute or chronic
      invasive fungal rhinosinusitis, or allergic fungal rhinosinusitis (AFRS). Given
      the variable spectrum of immune status and susceptibility to severe infection
      from opportunistic pathogens it is extremely important that clinicians
      distinguish aggressive fungal invasive fungal disease from the much milder forms
      such as AFRS. Here we describe a patient with HIV and AFRS to both remind
      providers of the importance of ruling out invasive fungal disease and outline the
      other unique features of fungal sinusitis treatment in the HIV-positive
      population. Additionally we discuss the evidence for and against use of allergen
      immunotherapy (AIT) for fungal disease in general, as well as the evidence for
      AIT in the HIV population. 

PMID- 25954558
TI  - Neuroinvasive cryptococcosis in an immunocompetent patient with a negative spinal
      fluid cryptococcus antigen.
AB  - 58-year-old man presented with headache, nausea, vomiting, and gait disturbance.
      Brain MRI showed meningeal enhancement and herniation. Serum Cryptococcus antigen
      was positive but spinal fluid antigen and cultures were negative. A cerebellar
      biopsy revealed nonencapsulated Cryptococcus. He completed antifungal therapy.
      Serum Cryptococcus antigen titer decreased. He had a full neurological recovery. 

PMID- 25954559
TI  - Neonatal urinary ascites: a report of three cases.
AB  - Urinary ascites in neonates is not a common condition. Three cases of urinary
      ascites are presented and each of them has a different aetiology. Neonates with
      urinary ascites usually present as clinical emergency, requiring resuscitation,
      ventilator support, and subsequent drainage of urine. The ultimate management
      depends on the site of extravasation and the underlying cause. 

PMID- 25954560
TI  - Successful reduction of acute puerperal uterine inversion with the use of a bakri
      postpartum balloon.
AB  - Uterine inversion is a state wherein the endometrial surface is inverted.
      Although this condition may be observed in nonpregnant women, it most commonly
      develops at the time of delivery. In the present case, a 37-year-old woman
      without any remarkable history developed acute puerperal uterine inversion after
      the successful induction of labor. Following the delivery, she complained twice
      of severe lower abdominal pain; subsequently, hemorrhage was noted at the site of
      partial detachment of the placenta. These findings led to a diagnosis of placenta
      accreta, and the patient developed a state of shock. A Bakri postpartum balloon
      was inserted into the uterine cavity under ultrasonographic guidance and was
      filled with physiological saline for treatment of this condition. With this
      procedure, the uterine inversion was completely reduced and the hemorrhage was
      stopped. Moreover, no reinversion was observed in the postoperative period. These
      findings suggest that a Bakri postpartum balloon can be used to noninvasively
      reduce uterine inversion and prevent its recurrence. 

PMID- 25954561
TI  - Polymorphous low-grade adenocarcinoma of the tongue base treated by transoral
      robotic surgery.
AB  - Polymorphous low-grade adenocarcinoma is a rare malignancy arising from the minor
      salivary glands in the aerodigestive system, most frequently the hard palate. The
      treatment of choice is wide surgical resection, and the efficacy of radiotherapy
      has not been confirmed. A 54-year-old male presenting with a mass at the base of
      the tongue performed transoral laser microsurgery. The pathologic diagnosis was
      polymorphous low-grade adenocarcinoma. Complete surgical excision was performed
      via transoral robotic surgery without a flap reconstruction of the surgical
      defect. Without complications of bleeding or injury to the hypoglossal nerve,
      proper surgical margins were obtained, and no recurrence was found after 6 months
      after surgery. The patient did not complain of dysphagia or aspiration. We
      conclude that, in surgery for tongue base tumors with unknown malignant
      potential, transoral robotic surgery can be considered for achieving a definite
      resection avoiding a mandibulotomy without complications of dysphagia or
      aspiration after confirmation of malignancy with a frozen biopsy. 

PMID- 25954562
TI  - Severe psychotic disorder as the main manifestation of adrenal insufficiency.
AB  - We describe a case of severe psychotic disorder as the only manifestation of
      primary adrenal insufficiency. A 63-year-old man presented with psychotic
      symptoms without any prior psychiatric history. During the clinical and
      laboratorial investigation, exams revealed a normovolemic hyponatremia. The
      patient showed no other clinical signs or symptoms compatible with adrenal
      insufficiency but displayed very high ACTH and low serum cortisol concentrations.
      Brain magnetic resonance imaging showed no significant changes, including the
      pituitary gland. The patient was initially treated with intravenous
      corticosteroids, resulting in rapid remission of the psychotic symptoms. The
      association between adrenal insufficiency and neuropsychiatric symptoms is rare
      but these symptoms can often be the first clinical presentation of the disease. 

PMID- 25954563
TI  - Simple lymphangioma to generalized lymphatic anomaly: role of imaging in
      disclosure of a rare and morbid disease.
AB  - Generalized lymphatic anomaly is a rare multisystem congenital disorder in which
      multiple organs are involved. Imaging features often overlap with other complex
      lymphatic anomalies and diagnosis is difficult. Treatment options are limited,
      not remedial and prognosis is poor. We report a 12-year-old male who presented
      with axillary and chest wall lymphangioma but was subsequently diagnosed as
      having diffuse lymphangiomatosis affecting lungs, liver, spleen, and bones on
      computerized tomography scan. We suggest complete radiological evaluation of
      susceptible adolescent children with lymphangioma to avoid diagnostic delay in
      this morbid condition. We also discuss radiological features of other similar
      complex lymphatic anomalies and crucial role of imaging in diagnosis. 

PMID- 25954564
TI  - Solitary plasmacytoma of the cecum and the ascending colon: surgical resection as
      a treatment modality.
AB  - Colonic solitary plasmacytoma is a rare disease, with few reports occurring in
      the literature. Solitary plasmacytoma is defined as a plasma cell tumour with no
      evidence of bone marrow infiltration. Plasmacytoma can present as a solitary
      tumour in bone or in other parts of the body. The gastrointestinal tract is
      rarely the site of the disease. We report on the case of a 51-year-old man
      presenting with a colonic symptomatic mass with unclear biopsy results. A
      resected specimen showed a solitary plasmacytoma. Surgical resection was an
      adequate treatment modality in this case. Endoscopic resection, radiotherapy, and
      chemotherapy are also preferred treatments in selected gastrointestinal
      plasmacytoma cases. 

PMID- 25954565
TI  - Discovery of Intra-Abdominal Hemorrhage during Hernioplasty in a Patient Taking
      Rivaroxaban.
AB  - We discuss the first ever case of rivaroxaban causing major intra-abdominal
      hemorrhage found in a patient during emergency hernioplasty. The source of
      bleeding was not identified either intra- or postoperatively. This is on a
      background of treatment for deep vein thrombosis (DVT) with rivaroxaban, a
      complication that resulted from a total knee arthroplasty performed four weeks
      prior. Rivaroxaban is a new generation of anticoagulants that directly inhibits
      factor Xa and is used for DVT treatment in major orthopaedic surgery. Here we
      discuss the major side effects of rivaroxaban, namely, the increased risk of
      major bleeding as well as the irreversibility of this anticoagulant, should such
      bleeding occur. We advise caution in the use of rivaroxaban even in patients that
      are at low risk of bleeding given the discovery of hemorrhage as presented in
      this case. 

PMID- 25954566
TI  - Urethrovaginal fistula in a 5-year-old girl.
AB  - Urethral fistulas are rare in girls. They occur most of the time during trauma.
      The case presented here is an iatrogenic fistula. The treatment was simple and
      consisted of a simple dissection and suture of urethra and vagina. 

PMID- 25954567
TI  - Peripheral Thrombosis and Necrosis after Minimally Invasive Redo Mitral Valve
      Replacement due to Unknown Etiology: Difficult Diagnosis of Heparin Induced
      Thrombocytopenia.
AB  - We report on a 75-year-old male with acute onset of peripheral thrombosis causing
      necrosis of the fingers, elbow, and toes associated with thrombocytopenia after
      minimally invasive redo mitral valve replacement. Both warfarin and dalteparin
      were commenced on postoperative day 1 and his INR reached 2.1 on postoperative
      day 4. On postoperative day 5, the patient developed peripheral thrombosis which
      progressed to necrosis on postoperative day 6. Platelet counts decreased
      significantly on the same day. His clinical features were compatible with heparin
      induced thrombocytopenia (HIT). However, serology testing was negative and the
      diagnosis was never confirmed. The patient was treated for HIT and platelet count
      improved eventually. Although no clear consensus exists, we believe this case
      illustrates why therapy for HIT should be initiated when clinical features
      strongly suggest HIT despite a negative serology test, unless an alternate
      diagnosis can be found. 

PMID- 25954569
TI  - Molecularly imprinted nanomicrospheres as matrix solid-phase dispersant combined
      with gas chromatography for determination of four phosphorothioate pesticides in
      carrot and yacon.
AB  - An efficient, rapid, and selective method for sample pretreatment, namely,
      molecularly imprinted matrix solid-phase dispersion (MI-MSPD) coupled with gas
      chromatography (GC), was developed for the rapid isolation of four
      phosphorothioate organophosphorus pesticides (tolclofos-methyl, phoxim,
      chlorpyrifos, and parathion-methyl) from carrot and yacon samples. New
      molecularly imprinted polymer nanomicrospheres were synthesized by using typical
      structural analogue tolclofos-methyl as a dummy template via surface grafting
      polymerization on nanosilica. Then, these four pesticides in carrot and yacon
      were extracted and adsorbed using the imprinted nanomicrospheres and further
      determined by gas chromatography. Under the optimized conditions, a good
      linearity of four pesticides was obtained in a range of 0.05-17.0 ng.g(-1) with R
      varying from 0.9971 to 0.9996, and the detection limit of the method was
      0.012~0.026 ng.g(-1) in carrot and yacon samples. The recovery rates at two
      spiked levels were in the range of 85.4-105.6% with RSD <=9.6%. The presented MI
      MSPD method combined the advantages of MSPD for allowing the extraction,
      dispersion, and homogenization in two steps and the advantages of MIPs for high
      affinity and selectivity towards four phosphorothioate pesticides, which could be
      applied to the determination of pesticide residues in complicated vegetal
      samples. 

PMID- 25954570
TI  - Implementing a Clinical Research Management System: One Institution's Successful
      Approach Following Previous Failures.
AB  - Clinical research management systems (CRMSs) can facilitate research billing
      compliance and clinician awareness of study activities when integrated with
      practice management and electronic health record systems. However, adoption of
      CRMSs remains low, and optimal approaches to implementation are unknown. This
      case report describes one institution's successful approach to organization,
      technology, and workflow for CRMS implementation following previous failures.
      Critical factors for CRMS success included organizational commitment to clinical
      research, a dedicated research information technology unit, integration of
      research data across disparate systems, and centralized system usage workflows.
      In contrast, previous failed approaches at the institution lacked a mandate and
      mechanism for change, received support as a business rather than research
      activity, maintained data in separate systems, and relied on inconsistent
      distributed system usage workflows. To our knowledge, this case report is the
      first to describe CRMS implementation success and failures, which can assist
      practitioners and academic evaluators. 

PMID- 25954571
TI  - Role of citation tracking in updating of systematic reviews.
AB  - We proposed to use automatic citation tracking to enhance the retrieval of new
      evidence for updating Systematic Reviews (SR). We tested on a Cochrane review
      from 2003 (updated 2010) and retrieved 12 of the papers to be added (recall
      85.7%). Citation tracking yields a high proportion of the required literature. 

PMID- 25954568
TI  - Liver fibrosis and mechanisms of the protective action of medicinal plants
      targeting inflammation and the immune response.
AB  - Inflammation is a central feature of liver fibrosis as suggested by its role in
      the activation of hepatic stellate cells leading to extracellular matrix
      deposition. During liver injury, inflammatory cells are recruited in the
      injurious site through chemokines attraction. Thus, inflammation could be a
      target to reduce liver fibrosis. The pandemic trend of obesity, combined with the
      high incidence of alcohol intake and viral hepatitis infections, highlights the
      urgent need to find accessible antifibrotic therapies. Medicinal plants are
      achieving popularity as antifibrotic agents, supported by their safety, cost
      effectiveness, and versatility. The aim of this review is to describe the role of
      inflammation and the immune response in the pathogenesis of liver fibrosis and
      detail the mechanisms of inhibition of both events by medicinal plants in order
      to reduce liver fibrosis. 

PMID- 25954572
TI  - Standard-based EHR-enabled applications for clinical research and patient safety:
      CDISC - IHE QRPH - EHR4CR & SALUS collaboration.
AB  - Integration profiles collaboratively developed by CDISC and IHE for integrating
      data from Electronic Health Records (EHRs) with clinical research and
      pharmacovigilance are limited to resolving lexical/syntactic data integration
      issues and do not address semantic barriers. This paper describes the
      collaboration between two European projects - EHR4CR and SALUS - in implementing
      ISO/IEC 11179-based metadata registries (MDRs) and semantically integrated cross
      platform data access. A common "semantic MDR" provides a framework for
      bidirectional/cross-MDR mapping and federated queries are enabled using the newly
      defined IHE Data Exchange (DEX) profile. In the pilot implementation, mappings
      for 178 EHR4CR and 199 SALUS metadata elements were persisted in the semantic
      MDR. The DEX profile was then used to access semantically equivalent data
      elements in SALUS or EHR4CR participating EHR systems. ISO/IEC 11179-based MDRs
      and DEX integration profile address the goal of developing pan-EU computable
      semantic integration of data from clinical care, clinical research, and patient
      safety platforms. 

PMID- 25954573
TI  - Simplifying complex clinical element models to encourage adoption.
AB  - Clinical Element Models (CEMs) were developed to provide a normalized form for
      the exchange of clinical data. The CEM specification is quite complex and
      specialized knowledge is required to understand and implement the models, which
      presents a significant barrier to investigators and study designers. To encourage
      the adoption of CEMs at the time of data collection and reduce the need for
      retrospective normalization efforts, we developed an approach that provides a
      simplified view of CEMs for non-experts while retaining the full semantic detail
      of the underlying logical models. This allows investigators to approach CEMs
      through generalized representations that are intended to be more intuitive than
      the native models, and it permits them to think conceptually about their data
      elements without worrying about details related to the CEM logical models and
      syntax. We demonstrate our approach using data elements from the Pharmacogenomics
      Research Network (PGRN). 

PMID- 25954574
TI  - Ontology-based tools to expedite predictive model construction.
AB  - Large amounts of medical data are collected electronically during the course of
      caring for patients using modern medical information systems. This data presents
      an opportunity to develop clinically useful tools through data mining and
      observational research studies. However, the work necessary to make sense of this
      data and to integrate it into a research initiative can require substantial
      effort from medical experts as well as from experts in medical terminology, data
      extraction, and data analysis. This slows the process of medical research. To
      reduce the effort required for the construction of computable, diagnostic
      predictive models, we have developed a system that hybridizes a medical ontology
      with a large clinical data warehouse. Here we describe components of this system
      designed to automate the development of preliminary diagnostic models and to
      provide visual clues that can assist the researcher in planning for further
      analysis of the data behind these models. 

PMID- 25954575
TI  - Extracting and standardizing medication information in clinical text - the MedEx
      UIMA system.
AB  - Extraction of medication information embedded in clinical text is important for
      research using electronic health records (EHRs). However, most of current
      medication information extraction systems identify drug and signature entities
      without mapping them to standard representation. In this study, we introduced the
      open source Java implementation of MedEx, an existing high-performance medication
      information extraction system, based on the Unstructured Information Management
      Architecture (UIMA) framework. In addition, we developed new encoding modules in
      the MedEx-UIMA system, which mapped an extracted drug name/dose/form to both
      generalized and specific RxNorm concepts and translated drug frequency
      information to ISO standard. We processed 826 documents by both systems and
      verified that MedEx-UIMA and MedEx (the Python version) performed similarly by
      comparing both results. Using two manually annotated test sets that contained 300
      drug entries from medication list and 300 drug entries from narrative reports,
      the MedEx-UIMA system achieved F-measures of 98.5% and 97.5% respectively for
      encoding drug names to corresponding RxNorm generic drug ingredients, and F
      measures of 85.4% and 88.1% respectively for mapping drug names/dose/form to the
      most specific RxNorm concepts. It also achieved an F-measure of 90.4% for
      normalizing frequency information to ISO standard. The open source MedEx-UIMA
      system is freely available online at http://code.google.com/p/medex-uima/. 

PMID- 25954577
TI  - Electronic health records and disease registries to support integrated care in a
      health neighbourhood: an ontology-based methodology.
AB  - Disease registries derived from Electronic Health Records (EHRs) are widely used
      for chronic disease management (CDM). However, unlike national registries which
      are specialised data collections, they are usually specific to an EHR or
      organization such as a medical home. We approached registries from the
      perspective of integrated care in a health neighbourhood, considering data
      quality issues such as semantic interoperability (consistency), accuracy,
      completeness and duplication. Our proposition is that a realist ontological
      approach is required to systematically and accurately identify patients in an EHR
      or data repository of EHRs, assess intrinsic data quality and fitness for use by
      members of the multidisciplinary integrated care team. We report on this approach
      as applied to routinely collected data in an electronic practice based research
      network in Australia. 

PMID- 25954576
TI  - Discovering associations among diagnosis groups using topic modeling.
AB  - With the rapid growth of electronic medical records (EMR), there is an increasing
      need of automatically extract patterns or rules from EMR data with machine
      learning and data mining technqiues. In this work, we applied unsupervised
      statistical model, latent Dirichlet allocations (LDA), to cluster patient
      diagnoics groups from Rochester Epidemiology Projects (REP). The initial results
      show that LDA holds the potential for broad application in epidemiogloy as well
      as other biomedical studies due to its unsupervised nature and great interpretive
      power. 

PMID- 25954579
TI  - Visualizing and evaluating the growth of multi-institutional collaboration based
      on research network analysis.
AB  - Research collaboration plays an important role in scientific productivity and
      academic innovation. Multi-institutional collaboration has become a vital
      approach for integrating multidisciplinary resources and expertise to enhance
      biomedical research. There is an increasing need for analyzing the effect of
      multi-institutional research collaboration. In this paper, we present a
      collaboration analysis pipeline based on research networks constructed from
      publication co-authorship relationship. Such research networks can be effectively
      used to render and analyze large-scale institutional collaboration. The co
      authorship networks of the Cleveland Clinical and Translational Science
      Collaborative (CTSC) were visualized and analyzed. SciVal ExpertTM was used to
      extract publication data of the CTSC members. The network was presented in
      informative and aesthetically appealing diagrams using the open source
      visualization package Gephi. The analytic result demonstrates the effectiveness
      of our approach, and it also indicates the substantial growth of research
      collaboration among the CTSC members crossing its partner institutions. 

PMID- 25954578
TI  - Detailed clinical modelling approach to data extraction from heterogeneous data
      sources for clinical research.
AB  - The reuse of routinely collected clinical data for clinical research is being
      explored as part of the drive to reduce duplicate data entry and to start making
      full use of the big data potential in the healthcare domain. Clinical researchers
      often need to extract data from patient registries and other patient record
      datasets for data analysis as part of clinical studies. In the TRANSFoRm project,
      researchers define their study requirements via a Query Formulation Workbench. We
      use a standardised approach to data extraction to retrieve relevant information
      from heterogeneous data sources, using semantic interoperability enabled via
      detailed clinical modelling. This approach is used for data extraction from data
      sources for analysis and for pre-population of electronic Case Report Forms from
      electronic health records in primary care clinical systems. 

PMID- 25954580
TI  - Semi-Supervised Learning to Identify UMLS Semantic Relations.
AB  - The UMLS Semantic Network is constructed by experts and requires periodic expert
      review to update. We propose and implement a semi-supervised approach for
      automatically identifying UMLS semantic relations from narrative text in PubMed.
      Our method analyzes biomedical narrative text to collect semantic entity pairs,
      and extracts multiple semantic, syntactic and orthographic features for the
      collected pairs. We experiment with seeded k-means clustering with various
      distance metrics. We create and annotate a ground truth corpus according to the
      top two levels of the UMLS semantic relation hierarchy. We evaluate our system on
      this corpus and characterize the learning curves of different clustering
      configuration. Using KL divergence consistently performs the best on the held-out
      test data. With full seeding, we obtain macro-averaged F-measures above 70% for
      clustering the top level UMLS relations (2-way), and above 50% for clustering the
      second level relations (7-way). 

PMID- 25954581
TI  - Open Source Clinical NLP - More than Any Single System.
AB  - The number of Natural Language Processing (NLP) tools and systems for processing
      clinical free-text has grown as interest and processing capability have surged.
      Unfortunately any two systems typically cannot simply interoperate, even when
      both are built upon a framework designed to facilitate the creation of pluggable
      components. We present two ongoing activities promoting open source clinical NLP.
      The Open Health Natural Language Processing (OHNLP) Consortium was originally
      founded to foster a collaborative community around clinical NLP, releasing UIMA
      based open source software. OHNLP's mission currently includes maintaining a
      catalog of clinical NLP software and providing interfaces to simplify the
      interaction of NLP systems. Meanwhile, Apache cTAKES aims to integrate best-of
      breed annotators, providing a world-class NLP system for accessing clinical
      information within free-text. These two activities are complementary. OHNLP
      promotes open source clinical NLP activities in the research community and Apache
      cTAKES bridges research to the health information technology (HIT) practice. 

PMID- 25954582
TI  - Towards Transforming Expert-based Content to Evidence-based Content.
AB  - The goal of this paper is to find relevant citations for clinicians' written
      content and make it more reliable by adding scientific articles as references and
      enabling the clinicians to easily update it using new information. The proposed
      approach uses information retrieval and ranking techniques to extract and rank
      relevant citations from MEDLINE for any given sentence. Additionally, this system
      extracts snippets of relevant content from ranked citations. We assessed our
      approach on 4,697 MEDLINE papers and their corresponding full-text on the subject
      of Heart Failure. We implemented multi-level and weight ranking algorithms to
      rank the citations. We demonstrate that using journal relevance and study design
      type improves results obtained from only using content similarity by
      approximately 40%. We also show that using full-text, rather than abstract text,
      leads to extracting higher quality snippets. 

PMID- 25954583
TI  - Detecting Associations between Major Depressive Disorder Treatment and Essential
      Hypertension using Electronic Health Records.
AB  - In this observational study, we investigate the correlation between depression
      and hypertension on a cohort of patients treated for major depressive disorder
      using Selective Serotonin Reuptake Inhibitors (SSRIs) and assess the effect of
      depression treatment on the diagnoses and treatment for essential hypertension.
      Our results indicate that the positive effect of successful depression treatment
      can be discovered and estimated from electronic health record (EHR) data even for
      a small sample size. We have also successfully detected differences in the effect
      of depression treatment in hypertensive patients between the two phenotypes
      representing successful treatment outcomes-response and remission- concluding
      that achieving remission has a longer lasting effect than response. 

PMID- 25954584
TI  - Variation in Cohorts Derived from EHR Data in Four Care Delivery Settings.

PMID- 25954585
TI  - Enhancing electronic health records to support clinical research.
AB  - The "Learning Health System" has been described as an environment that drives
      research and innovation as a natural outgrowth of patient care. Electronic health
      records (EHRs) are necessary to enable the Learning Health System; however, a
      source of frustration is that current systems fail to adequately support research
      needs. We propose a model for enhancing EHRs to collect structured and standards
      based clinical research data during clinical encounters that promotes efficiency
      and computational reuse of quality data for both care and research. The model
      integrates Common Data Elements (CDEs) for clinical research into existing
      clinical documentation workflows, leveraging executable documentation guidance
      within the EHR to support coordinated, standardized data collection for both
      patient care and clinical research. 

PMID- 25954586
TI  - Using software to elicit user needs for clinical research visit scheduling.
AB  - User needs understanding is critical for developing useful and usable clinical
      research decision support. Existing methods largely depend on self-reporting and
      often fail to elicit implicit or fine-grained user needs. We hypothesized that
      functional software would address this problem by presenting to users existing
      technology while simultaneously encouraging users to optimize workflow. Using
      clinical research visit scheduling as an example, we used a piece of software
      under development that was called IMPACT to reveal user needs iteratively. The
      identified user needs explained why most clinical research coordinators still
      rely on paper to schedule clinical research visits. The common user needs themes
      such as information completeness for software to be useful may generalize to
      other clinical decision support. This paper contributes valuable firsthand
      knowledge about user needs for decision support for clinical research visit
      scheduling among clinical research coordinators and a generalizable methodology
      for collecting and analyzing software usage data to inform user needs
      elicitation. 

PMID- 25954587
TI  - Temporal analysis of the usage log of a research networking system.
AB  - Despite the proliferation of research networking systems (RNS), their value and
      usage remains unknown. This study aims to characterize the temporal usage of an
      RNS, Columbia University Scientific Profiles (CUSP), and to inform the designs of
      general RNSs. We installed a free usage logging service, Google Analytics, on
      CUSP and applied time series analysis to compare the usage patterns of the two
      modes of CUSP: restricted (authenticated) and open access. More users searched by
      person names than by topics, although the latter enables in-depth vertical search
      of co-author or co-investigator networks for grants or publications. The open
      access mode received more page views but less average time spent on each page
      than the restricted access mode. The numbers of unique users and searches have
      increased over the time. This study contributes a trend analysis framework for
      understanding the usage of RNSs and early knowledge of the usage of an open
      access RNS. 

PMID- 25954588
TI  - On the Bayesian Derivation of a Treatment-based Cancer Ontology.
AB  - Traditional cancer classifications are primarily based on anatomical locations.
      As knowledge is heavily compartmentalized in the oncological specialties,
      discovering new targets for existing drugs (drug inference) can take years.
      Furthermore, our lack of understanding of the mechanisms underlying drug efficacy
      sometimes undercuts the effectiveness of genetic approaches to drug inference.
      This study tackles the twin problems of cancer reclassification and drug
      inference by constructing a global cancer ontology inductively from treatment
      regimens. A topological abstraction algorithm was performed on the bipartite
      graph of drugs and cancers to highlight important edges, and a Bayesian algorithm
      was then applied to determine a new treatment-based classification of cancer,
      producing 6 highly significant clusters (p < 0.05), confirmed by Fisher's exact
      test and enrichment analyses. Edge probabilities derived from its drug inference
      routine matched real edge frequencies (R2 ~ 0.96). Drug inference results were
      reinforced by the identification of relevant published Phase II and III clinical
      trials, and the drug inference routine differentiated between high- and low
      likelihood targets (p < 0.05). This novel treatment-based ontology has the
      potential to reorganize cancer research and provide powerful tools for drug
      inference using global patterns of drug efficacy. 

PMID- 25954589
TI  - Toward a cognitive task analysis for biomedical query mediation.
AB  - In many institutions, data analysts use a Biomedical Query Mediation (BQM)
      process to facilitate data access for medical researchers. However, understanding
      of the BQM process is limited in the literature. To bridge this gap, we performed
      the initial steps of a cognitive task analysis using 31 BQM instances conducted
      between one analyst and 22 researchers in one academic department. We identified
      five top-level tasks, i.e., clarify research statement, explain clinical process,
      identify related data elements, locate EHR data element, and end BQM with either
      a database query or unmet, infeasible information needs, and 10 sub-tasks. We
      evaluated the BQM task model with seven data analysts from different clinical
      research institutions. Evaluators found all the tasks completely or semi-valid.
      This study contributes initial knowledge towards the development of a
      generalizable cognitive task representation for BQM. 

PMID- 25954590
TI  - Cross-system evaluation of clinical trial search engines.
AB  - Clinical trials are fundamental to the advancement of medicine but constantly
      face recruitment difficulties. Various clinical trial search engines have been
      designed to help health consumers identify trials for which they may be eligible.
      Unfortunately, knowledge of the usefulness and usability of their designs remains
      scarce. In this study, we used mixed methods, including time-motion analysis,
      think-aloud protocol, and survey, to evaluate five popular clinical trial search
      engines with 11 users. Differences in user preferences and time spent on each
      system were observed and correlated with user characteristics. In general,
      searching for applicable trials using these systems is a cognitively demanding
      task. Our results show that user perceptions of these systems are multifactorial.
      The survey indicated eTACTS being the generally preferred system, but this
      finding did not persist among all mixed methods. This study confirms the value of
      mixed-methods for a comprehensive system evaluation. Future system designers must
      be aware that different users groups expect different functionalities. 

PMID- 25954591
TI  - Application of HL7/LOINC Document Ontology to a University-Affiliated Integrated
      Health System Research Clinical Data Repository.
AB  - Fairview Health Services is an affiliated integrated health system partnering
      with the University of Minnesota to establish a secure research-oriented clinical
      data repository that includes large numbers of clinical documents.
      Standardization of clinical document names and associated attributes is essential
      for their exchange and secondary use. The HL7/LOINC Document Ontology (DO) was
      developed to provide a standard representation of clinical document attributes
      with a multi-axis structure. In this study, we evaluated the adequacy of DO to
      represent documents in the clinical data repository from legacy and current EHR
      systems across community and academic practice sites. The results indicate that a
      large portion of repository data items can be mapped to the current DO ontology
      but that document attributes do not always link consistently with DO axes and
      additional values for certain axes, particularly "Setting" and "Role" are needed
      for better coverage. To achieve a more comprehensive representation of clinical
      documents, more effort on algorithms, DO value sets, and data governance over
      clinical document attributes is needed. 

PMID- 25954592
TI  - Enzymatic C(sp3)-H Amination: P450-Catalyzed Conversion of Carbonazidates into
      Oxazolidinones.
AB  - Cytochrome P450 enzymes can effectively promote the activation and cyclization of
      carbonazidate substrates to yield oxazolidinones via an intramolecular nitrene C
      H insertion reaction. Investigation of the substrate scope shows that while
      benzylic/allylic C-H bonds are most readily aminated by these biocatalysts,
      stronger, secondary C-H bonds are also accessible to functionalization.
      Leveraging this "non-native" reactivity and assisted by fingerprint-based
      predictions, improved active-site variants of the bacterial P450 CYP102A1 could
      be identified to mediate the aminofunctionalization of two terpene natural
      products with high regio- and stereoselectivity. Mechanistic studies and KIE
      experiments show that the C-H activation step in these reactions is rate-limiting
      and proceeds in a stepwise manner, namely, via hydrogen atom abstraction followed
      by radical recombination. This study expands the reactivity scope of P450-based
      catalysts in the context of nitrene transfer transformations and provides first
      time insights into the mechanism of P450-catalyzed C-H amination reactions.

PMID- 25954593
TI  - Knowledge and skills for management of sexually transmitted infections among
      rural medical practitioners in Bangladesh.
AB  - Sexually transmitted infection (STI) management is considered rudimentary among
      rural medical practitioners (RMPs) in Bangladesh. We sought to understand the
      level of knowledge and skills in STI management and to assess the impact of a two
      day training orientation among RMPs in Tangail district. Data were collected
      through a baseline survey of 225 practicing RMPs in the study area and a three
      month follow-up survey of 99 RMPs who participated in a two-day STI/HIV
      orientation training. The level of formal training among RMPs ranged from none
      (22.7%), to paramedical training (14.7%) and local medical assistant training
      (62.6%). The baseline survey revealed a low level of STI/HIV knowledge and
      misconceptions about the transmission of STI/HIV among RMPs. RMPs mostly
      prescribed first line antibiotics for treatment of common reproductive tract
      infections (RTIs) including STIs, but they rarely prescribed the correct dosages
      according to the national RTI/STI management guidelines. Only 3% of RMPs were
      able to correctly answer all four HIV transmission (unprotected sexual
      intercourse, blood transfusion, needle sharing and mother to child transmission)
      questions at baseline, while 94.9% of RMPs answered all four correctly at three
      months following the training (p=0.001). Only 10% of RMPs reported suggesting the
      recommended drug (azithromycin) and only 2% mentioned about the recommended
      dosage (2gm single dose) for the treatment of urethritis/cervicitis; compared to
      49.5% suggested azithromycin at follow-up with 39.4% mentioned the recommended
      2gm single dose (p=0.001). Our study found low level of knowledge and poor
      practices related RTI/STI management among RMPs. Short orientation training and
      education intervention shown promise to increase knowledge and management skills
      for RTIs/STIs.

PMID- 25954594
TI  - Do novo del(9)(p13) in a childhood T-cell prolymphocytic leukemia as sole
      abnormality.
AB  - T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive subtype of
      chronic lymphocytic leukemia. Usually it presents in older people with a median
      age of 61 years. T-PLL is characterized by elevated white blood cell (WBC) count
      with anemia and thrombocytopenia, hepatosplenomegaly, and lymphadenopathy; less
      common findings are skin infiltration and pleural effusions. The most frequent
      chromosomal abnormalities in T-PLL include 14q11.2, chromosome 8, and 11q
      rearrangements. Also deletions in the short arm of a chromosome 9 are reported in
      ~30% of T-PLL together with other aberrations. Here we report a childhood T-PLL
      case with a de novo del(9)(p13) as sole acquired anomaly leading to monosomy of
      the tumor suppressor gene CDKN2A (cyclin-dependent kinase inhibitor 2A). Also, to
      the best of our knowledge this is the first case of a childhood T-PLL with this
      aberration. 

PMID- 25954595
TI  - Effective long-term treatment with bevacizumab for relapsed glioblastoma: case
      report and review of the literature.
AB  - Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in
      adults. Despite the use of optimized first-line therapy, GBM is still associated
      with a poor prognosis and an effective second-line therapy remains an important
      challenge in this patient population. In 2009, the US Food and Drug
      Administration (FDA) approved the monoclonal anti-VEGF-antibody bevacizumab for
      the treatment of relapsed GBM after two phase-II studies showed its efficacy and
      safety, alone or in combination with irinotecan, in relapsed GBM. In contrast,
      the European Medicines Agency (EMA) concluded from the same published data that a
      clear benefit in terms of overall survival was not shown and subsequently did not
      grant approval for bevacizumab in this setting. Here, we report on a 53-year old
      patient with relapsed GBM who was treated with bevacizumab as single agent. After
      three months, the tumor volume was reduced and the Karnofsky performance status
      was substantially improved compared to the baseline at the time of relapse. After
      continued long-term treatment for 26 months, the patient remains in an excellent
      general condition. Moreover, the measurement of the tumor volume using multiple
      imaging modalities shows a sustained treatment response. In conclusion, this case
      supports the notion that individual patients respond exceptionally well to
      treatment with anti-VEGF therapy and suggests that future trials are needed to
      better identify the patient population that responds to bevacizumab. 

PMID- 25954596
TI  - TAM macrophages promote growth and metastasis within the cancer ecosystem.
AB  - Cancer continues to be the major cause of morbidity and death of more than
      500,000 people in the US annually. Alternatively activated macrophages (M2
      macrophages or TAMs) can facilitate tumor invasiveness and metastasis. As an
      invasive species in the tumor microenvironment, they provide an ideal therapeutic
      target.

PMID- 25954598
TI  - Healing after death: antitumor immunity induced by oncolytic adenoviral therapy.
AB  - We recently evaluated the capacity of Delta-24-RGD oncolytic adenovirus to
      trigger an antitumor immune response in a syngeneic mouse glioma model. This
      virotherapy elicited immunity against both tumor-associated antigens and viral
      antigens. An immunogenic cell death accompanied by pathogen- or damage-
      associated patterns (PAMPs and DAMPs) induced by the virus may be responsible for
      the adenoviral-mediated antitumor effect.

PMID- 25954599
TI  - High-Risk Populations: The Pimas of Arizona and Mexico.
AB  - The purpose of this review is first, to broadly summarize the long-term
      commitment that began in 1965 to studying type 2 diabetes and obesity through the
      cooperation of the Pima Indians of Arizona, and second, to discuss the
      investigations with the Pima Indians of Mexico that started in 1991. The later
      studies emphasize gene-environment interactions in the pathogenesis of these
      metabolic disorders. Through the participation of both groups of Pimas, the
      researchers made key findings with regard to the epidemiology, physiology,
      clinical assessment and genetics of type 2 diabetes and obesity. 

PMID- 25954597
TI  - Anti-melanoma vaccines engineered to simultaneously modulate cytokine priming and
      silence PD-L1 characterized using ex vivo myeloid-derived suppressor cells as a
      readout of therapeutic efficacy.
AB  - Efficacious antitumor vaccines strongly stimulate cancer-specific effector T
      cells and counteract the activity of tumor-infiltrating immunosuppressive cells.
      We hypothesised that combining cytokine expression with silencing programmed cell
      death ligand 1 (PD-L1) could potentiate anticancer immune responses of
      lentivector vaccines. Thus, we engineered a collection of lentivectors that
      simultaneously co-expressed an antigen, a PD-L1-silencing shRNA, and various T
      cell-polarising cytokines, including interferon gamma (IFNgamma), transforming
      growth factor beta (TGFbeta) or interleukins (IL12, IL15, IL23, IL17A, IL6, IL10,
      IL4). In a syngeneic B16F0 melanoma model and using tyrosinase related protein 1
      (TRP1) as a vaccine antigen, we found that simultaneous delivery of IL12 and a PD
      L1-silencing shRNA was the only combination that exhibited therapeutically
      relevant anti-melanoma activities. Mechanistically, we found that delivery of the
      PD-L1 silencing construct boosted T cell numbers, inhibited in vivo tumor growth
      and strongly cooperated with IL12 cytokine priming and antitumor activities.
      Finally, we tested the capacities of our vaccines to counteract tumor
      infiltrating myeloid-derived suppressor cell (MDSC) activities ex vivo.
      Interestingly, the lentivector co-expressing IL12 and the PD-L1 silencing shRNA
      was the only one that counteracted MDSC suppressive activities, potentially
      underlying the observed anti-melanoma therapeutic benefit. We conclude that (1)
      evaluation of vaccines in healthy mice has no significant predictive value for
      the selection of anticancer treatments; (2) B16 cells expressing xenoantigens as
      a tumor model are of limited value; and (3) vaccines which inhibit the
      suppressive effect of MDSC on T cells in our ex vivo assay show promising and
      relevant antitumor activities.

PMID- 25954600
TI  - Facebook for Health Promotion: Female College Students' Perspectives on Sharing
      HPV Vaccine Information Through Facebook.
AB  - Facebook, a social network site, has been widely used among young adults.
      However, its potential to be used as a health promotion medium has not been fully
      examined. This study explored Facebook's potential for sharing human
      papillomavirus (HPV) vaccine information among female college students in
      Hawai'i. Culturally tailored flyers and handouts were developed and distributed
      at one large university in Hawai'i to recruit female college students between the
      age of 18 and 26 having an active Facebook account. Three focus group meetings
      were conducted to gather student perspectives about how information about HPV
      vaccine may be best shared via Facebook. We found that students believed Facebook
      is a good awareness tool but they needed more knowledge about the HPV vaccine to
      feel comfortable sharing the information. Participants preferred forwarding
      information to chatting about HPV. Some participants expressed concern that their
      Facebook friends would think the HPV vaccine information they forwarded on
      Facebook is spam. Participants suggested prefacing the posted HPV vaccine
      information with a personal note in their own words to make the message more
      interesting and relevant to their Facebook friends. Future interventions using
      Facebook to promote HPV vaccine could provide students with HPV vaccine
      information from credible sources and ask students to attach personal
      testimonials or endorsements while forwarding the information on Facebook. 

PMID- 25954601
TI  - Investigation of Stroke Needs (INVISION) Study: Stroke Awareness and Education.
AB  - The objective of this study was to assess the overall understanding and
      effectiveness of current inpatient stroke education practice by using the data
      from the Investigation of Stroke Needs (INVISION) Study, a qualitative study
      assessing various challenges and barriers of the hemorrhagic stroke survivors and
      their caregivers. Semi-structured interviews were conducted on patients who were
      recently hospitalized with intracerebral hemorrhage (ICH) and their caregivers
      during the follow-up visits. The electronic medical record for each patient was
      reviewed to assess whether they received standard stroke education material
      during their hospitalization. A phenomenological approach was utilized to
      identify gaps of education and knowledge in the targeted sample. A total of 21
      participants were interviewed. Despite receiving formal stroke education material
      during their hospitalization, there were three major gaps in stroke knowledge
      that participants noted, including (1) lack of stroke knowledge/awareness, (2)
      need for stroke education, and (3) fear of recurrent stroke and comorbid
      diseases. The majority of ICH survivors had no memory of their hospitalization.
      This study suggests a need for increased continuity and communication with health
      care providers to address the evolving educational and practical needs of stroke
      patients and their caregivers after hospital discharge. 

PMID- 25954602
TI  - Weight reduction among people with severe and persistent mental illness after
      health behavior counseling and monitoring.
AB  - The high prevalence of obesity and associated chronic conditions in persons with
      severe and persistent mental illness has contributed to a mortality rate that is
      nearly two times higher than the overall population. In 2008, the Central O'ahu
      Community Mental Health Center of the Hawai'i State Department of Health, Adult
      Mental Health Division began an unfunded, health counseling intervention pilot
      project to address such concerns for the health of persons with severe and
      persistent mental illness. This article reviews the results of this intervention.
      Forty-seven persons with schizophrenia or related disorders were included in the
      intervention which involved health counseling and monitoring of weight as a risk
      factor for chronic disease. After five years of counseling and monitoring,
      medical chart reviews were conducted for each person for data on weight change.
      Analysis showed weight loss and improvements in body mass index. The results of
      this project show potential for long-term counseling and monitoring as an
      intervention for obesity in persons with severe and persistent mental illness. 

PMID- 25954604
TI  - Insights in public health: the tobacco settlement special fund: how investments
      in prevention save lives and dollars.

PMID- 25954603
TI  - Medical school hotline: the research mission of the cell and molecular biology
      department and program at the john a. Burns school of medicine.

PMID- 25954606
TI  - Commentary: "prom1 function in development, intestinal inflammation, and
      intestinal tumorigenesis".

PMID- 25954607
TI  - Clinical Significance of NOTCH1 and NOTCH2 Expression in Gastric Carcinomas: An
      Immunohistochemical Study.
AB  - BACKGROUND: NOTCH signaling can exert oncogenic or tumor suppressive functions
      and can contribute to chemotherapy resistance in cancer. In this study, we aimed
      to clarify the clinicopathological significance and the prognostic and predictive
      value of NOTCH1 and NOTCH2 expression in gastric cancer (GC). METHODS: NOTCH1 and
      NOTCH2 expression was determined immunohistochemically in 142 primarily resected
      GCs using tissue microarrays and in 84 pretherapeutic biopsies from patients
      treated by neoadjuvant chemotherapy. The results were correlated with survival,
      response to therapy, and clinico-pathological features. RESULTS: Primarily
      resected patients with NOTCH1-negative tumors demonstrated worse survival. High
      NOTCH1 expression was associated with early-stage tumors and with significantly
      increased survival in this subgroup. Higher NOTCH2 expression was associated with
      early-stage and intestinal-type tumors and with better survival in the subgroup
      of intestinal-type tumors. In pretherapeutic biopsies, higher NOTCH1 and NOTCH2
      expression was more frequent in non-responding patients, but these differences
      were statistically not significant. CONCLUSION: Our findings suggested that, in
      particular, NOTCH1 expression indicated good prognosis in GC. The close
      relationship of high NOTCH1 and NOTCH2 expression with early tumor stages may
      indicate a tumor-suppressive role of NOTCH signaling in GC. The role of NOTCH1
      and NOTCH2 in neoadjuvantly treated GC is limited.

PMID- 25954608
TI  - A cadaveric study of bilateral configuration of posterior bifurcation of
      posterior communicating artery in Indian population.
AB  - INTRODUCTION: Various studies have been done regarding variations of circle of
      Willis, but few literatures are available about the detail configurations on
      Indian population. Posterior communicating artery is the main collateral channel
      between the vertebrobasilar and carotid system. It may act as a main source of
      blood flow via posterior cerebral artery if fetal configuration is present. Aim
      of the study is to see the bilateral configurations to compare the blood supply
      of both cerebral hemispheres via posterior cerebral artery in human cadavers.
      MATERIALS AND METHODS: Fifty six formalin fixed brains were used for study. The
      specimens were classified into 3 types and 21 subtypes according to the
      configuration of the vessel of both hemispheres. As hemodynamic balance is
      dependent on the calibre of the vessel, the diameter of the arteries were also
      taken into consideration. Pearson's correlation had been done. RESULT: In present
      study type I is 57.2%, type II is 37.5% and type III is 5.4%. Incidence of
      unilateral fetal type posterior cerebral artery is in high percentage (33.9%).
      Greatest diameter of posterior communicating artery is 3.8mm on right and 3.6mm
      on left side. Significant correlations also have been found between arterial
      segments of different types. CONCLUSION: It is expected that the study will help
      to enrich the knowledge about the arterial predominance of origin of posterior
      cerebral artery of both cerebral hemispheres in normal or variant cases and its
      effect on perfusion images.

PMID- 25954609
TI  - Accessory pancreatic duct patterns and their clinical implications.
AB  - CONTEXT AND OBJECTIVE: Accessory pancreatic duct (APD) designed to reduce the
      pressure of major pancreatic duct by forming a secondary drainage channel. Few
      studies have mentioned the variant types of accessory ducts and their mode of
      formation, some of these have a clear clinical significance. Present study is
      aimed to evaluate the possible variations in the APD and its terminations.
      MATERIALS AND METHODS: Forty formalin fixed adult human pancreas with duodenum in
      situ specimens were studied by injecting 1% aqueous eosin, followed by piece meal
      dissection of the head of the pancreas from posterior surface. Formation,
      tributaries, relations, and the termination of the accessory pancreatic duct were
      noted and photographed. RESULTS: Accessory ducts revealed 50% belonged to long
      type, 22.5% were of short and ansa pancreatica type each, and embryonic type of
      duct pattern was seen in 5% specimens. 75% of long type ducts showed positive
      patency with eosin dye, followed by ansa type (44.4%), and least patency was
      found in short type (22.2%). With regard to the patency of the accessory
      pancreatic ducts towards their termination, we found 52.5% of the accessory ducts
      and 5% of the embryonic type pancreatic ducts were patent and in 42.5% of the
      specimen the ducts were obliterated. In 85% of specimens the minor duodenal
      papillae was anterosuperior to the major papilla and superior to the major
      papillae in 10% of the cases, and in 5% minor papillae was absent. The average
      distance between the two papillae was 2.35 cm. CONCLUSION: The knowledge of the
      complex anatomical relations of the gland with its duct, duodenum and bile ducts
      are essential for the surgeons and sinologists to plan and perform both the
      diagnostic as well as therapeutic procedures effectively.

PMID- 25954610
TI  - Anatomical variations in the pattern of the right hepatic veins draining the
      posterior segment of the right lobe of the liver.
AB  - BACKGROUND: The pattern of drainage in the right posterior lobe of liver varies
      considerably. The knowledge of this variation is very important while performing
      various surgeries on the right posterior lobe. AIM: A study was conducted to see
      the variations in the pattern of drainage of posterior segment of the right lobe
      of liver. The aim was to see the variations of right hepatic vein and small
      accessory hepatic veins draining the posterior segment, the presence of which led
      to modifications in drainage of posterior segment. MATERIAL AND METHODS: Sixty
      formalin fixed adult human liver specimens were dissected manually. RESULTS:
      According to the pattern of drainage of tributaries of right hepatic vein, the
      right hepatic vein was classified into type I, type II, type III and type IV.
      According to presence of inferior right hepatic vein, three types of drainage of
      posterior lobe were seen: Type I, (76.36%) right hepatic vein was large, draining
      wide area of posterior segment. A small inferior right hepatic vein drained the
      small area of posterior segment. In Type II, (19.92%) both right hepatic and
      inferior right hepatic veins were medium sized draining the posteroinferior
      segment of the right lobe concomitantly. In Type III, (32%) accessory veins, the
      middle right hepatic vein drained the posterosuperior (VII) as well as the
      posteroinferior (VI) segment. In one specimen, there were numerous middle right
      hepatic veins draining the right posterior segment. The knowledge of anatomic
      relationship of veins draining right lobe, is important in performing right
      posterior segmentectomy. CONCLUSION: For safe resection of the liver, the complex
      anatomy of the distribution of the tributaries of the right hepatic vein and the
      accessory veins have to be studied prior to any surgery done on liver.

PMID- 25954611
TI  - Anatomy of axillary nerve and its clinical importance: a cadaveric study.
AB  - INTRODUCTION: Axillary nerve is one of the terminal branches of posterior cord of
      brachial plexus, which is most commonly injured during numerous orthopaedic
      surgeries, during shoulder dislocation & rotator cuff tear. All these possible
      iatrogenic injuries are because of lack of awareness of anatomical variations of
      the nerve. Therefore, it is very much necessary to explore its possible
      variations and guide the surgeons to enhance the better clinical outcome by
      reducing the risk and complications. MATERIALS AND METHODS: Twenty five cadavers
      (20 Males & 05 Females) making 50 specimens including both right and left sides
      were dissected as per standard dissection methods to find the origin, course,
      branches, distribution & exact location of the nerve beneath the deltoid muscle
      from important landmarks like: posterolateral aspect of acromion process,
      anteromedial aspect of tip of coracoid process, midpoint of deltoid muscle
      insertion (deltoid tuberosity of humerus) and from the midpoint of vertical
      length of deltoid muscle. The measurements were recorded and tabulated.
      STATISTICAL ANALYSIS: The measurements were entered in Microsoft excel and mean,
      proportion, standard deviation were calculated by using SPSS 16th version.
      RESULTS: The axillary nerve was found to take origin from the posterior cord of
      brachial plexus (100%) dividing into anterior & posterior branches in
      Quadrangular space (88%) and supply deltoid muscle mainly. It also gave branches
      to teres minor muscle, shoulder joint capsule & superolateral brachial cutaneous
      nerve (100%). This study concluded that the mean distance of axillary nerve from
      the - anteromedial aspect of tip of coracoid process, posterolateral aspect of
      acromion process, midpoint of deltoid insertion & from the midpoint of vertical
      length of deltoid muscle measured to be (in cm) as 3.56+/-0.51, 7.4+/-0.99, 6.7+/
      0.47 & 2.45+/-0.48 respectively. The mean vertical distance of entering point of
      axillary nerve from the anterior upper, mid middle upper & posterior upper
      deltoid border found to be (in cm): 4.94+/-0.86, 5.14+/-0.90 & 5.44+/-0.95
      respectively and the horizontal anterior & horizontal posterior mean distance
      being 4.54+/-0.65 & 3.22+/-0.53 respectively. The mean height, mean width & mean
      depth of Quadrangular space measured to be (in cm): 2.23+/-0.40, 2.19+/-0.22 &
      1.25+/-0.14 respectively. CONCLUSION: The findings were found to be highly
      significant when males were compared with females but not significant when sides
      (right & left) were compared.

PMID- 25954612
TI  - Unusual Communications between the Cutaneous Branches of Ulnar Nerve in the Palm.
AB  - Variations of dorsal and volar digital cutaneous branches of ulnar nerve are of
      tremendous clinical importance for successful regional nerve blocks, skin flaps,
      carpal tunnel release and placement of electrodes for electrophysiological
      studies. With the aforementioned clinical implications it is worth to report the
      variations of cutaneous branches of ulnar nerve. In the current case, we have
      encountered a rare variation (Kaplan's anastomosis) of ulnar nerve, in the right
      upper limb. We have noticed that the dorsal cutaneous branch of ulnar nerve
      divided into three branches, the lateral two branches supplied the skin of the
      medial one and half fingers of the dorsum of hand. The medial branch established
      communications with the superficial branches of ulnar nerve and distributed to
      the skin of the one and half fingers of the volar aspect of hand. The possible
      outcome of this communications is discussed. Course and distribution of ulnar
      nerve on the contralateral side was found to be normal. 

PMID- 25954614
TI  - Association of leukocyte telomere length with oxidative stress in yoga
      practitioners.
AB  - OBJECTIVE: Yoga is a mind-body modulation technique that has been shown to have
      beneficial effects on various diseases related to various systems in the body.
      However, the molecular basis of mechanism of action is not clear. Hence, this
      study was designed to study the leukocyte telomere biology and its relation with
      homocysteine and oxidative stress in yoga practitioners. MATERIALS AND METHODS:
      This is a prospective case-control study involving Yoga practitioners aged 30-40
      y with minimum of two years yoga practice (Yoga group) and age, gender and body
      mass index matched sedentary healthy general population with no medical problems
      (Control group). Leukocyte telomere length (LTL) was measured by using
      quantitative PCR (qPCR), fasting plasma homocysteine was measured by a rapid high
      performance liquid chromatography assay and the oxidative stress was assessed
      with total antioxidant status (TAOS), malondialdehyde (MDA) measured by
      calorimetry. RESULTS: The LTL was shorter in control group than in yoga group
      (p<0.001). The TAOS was more in yoga group when compared to control group
      (p=0.008), MDA and homocysteine was high in control group when compared to Yoga
      group (p<0.001). Further, the LTL was positively correlated with TAOS (r=0.841,
      p<0.001) and negatively correlated with MDA (r=-0.931, p<0.001) and Homocysteine
      (r=-0.756, p<0.001). CONCLUSION: The LTL is well-preserved in people who practice
      Yoga regularly with lower systemic oxidative stress compared to those who have a
      relatively sedentary lifestyle despite lack of any medical disorders. The
      habitual yoga practice seems to inhibit replicative cellular senescence.

PMID- 25954613
TI  - Is urolithiasis associated with increased levels of high sensitivity C-reactive
      protein and interleukin-6 in diabetic patients?
AB  - BACKGROUND: The prevalence and incidence of urolithiasis is increasing worldwide.
      Type 2 diabetes mellitus is well known to be associated with insulin resistance
      which increases the risk of urolithiasis by altering the composition of urine.
      Both urolithiasis and diabetes mellitus are associated with inflammation. The aim
      of the study was to assess the serum levels of inflammatory markers i.e. high
      sensitivity C-reactive protein (hsCRP) and Interleukin-6 (IL-6) in diabetes
      mellitus patients with urolithiasis in comparison to those without urolithiasis.
      MATERIALS AND METHODS: The study involved two groups. Group A consisted of
      diabetic mellitus patients with urolithiasis (n=30) and Group B consisted of
      diabetic mellitus patients without urolithiasis (n=30). Blood samples were
      obtained and analysed for HbA1C, lipid profile, calcium, phosphate and uric acid,
      and inflammatory markers (C-reactive protein and Interleukin-6) were also
      measured. RESULTS: We found a significant increase in CRP and IL-6 levels in
      diabetic urolithiasis cases as compared to diabetes mellitus cases without
      urolithiasis. However, no significant difference was observed in calcium,
      phosphorus and uric acid in diabetic patients with and without urolithiasis. We
      also found that total cholesterol, triglycerides, LDL-cholesterol and VLDL
      cholesterol levels were significantly increased, and HDL-cholesterol was
      significantly decreased in diabetic urolithiasis cases. IL-6 was significantly
      correlated with total cholesterol in diabetic urolithiasis cases. CONCLUSION: The
      data from the present study shows that lipid profile is altered, and Interleukin
      6 and C-reactive protein levels are significantly increased in patients with
      diabetes mellitus and urolithiasis when compared to diabetes mellitus alone.

PMID- 25954615
TI  - A comparative study of bacterial and parasitic intestinal infections in India.
AB  - BACKGROUND: Infectious diarrhea causes a major health problem in developing
      countries with significant morbidity and mortality. Very often, rehydration
      therapy alone does not suffice, mandating the use of antimicrobial agents.
      However, rapidly decreasing antimicrobial susceptibility is complicating the
      matters. MATERIALS AND METHODS: The study aimed to determine the prevalent
      bacterial and parasitic agents of diarrhea in India. A cross-sectional study was
      done at Maulana Azad Medical College and associated Lok Nayak Hospital, New
      Delhi, during 2012-14. Stool samples were received from patients of all age
      groups and processed for bacteriological and parasitological identification by
      microscopy, bacterial culture, biochemical identification, serotyping and
      antimicrobial susceptibility tests. The study also aimed to identify the recent
      papers (after year 2000) reporting aetiology of infectious diarrhea in India
      involving the general population as a whole and compare them with present
      findings. RESULTS: Out of 6527 samples, 581 (8.90%) were positive for bacterial
      pathogens. A total of 280 samples (of 3823 under-five year children) were
      positive for diarrheagenic Escherichia coli. Other organisms like Vibrio cholera
      were found in 159 (2.44%) cases, Shigella spp. in 126 (1.93%), Salmonella Typhi
      in 7 (0.11%), Salmonella Typhimurium in 6 (0.10%), Aeromonas hydrophila in 3
      (0.05%) cases. Levels of resistance to nalidixic acid, amoxicillin and
      ciprofloxacin were alarmingly high. Third generation cephalosporins were seen to
      be moderately active except against E. coli. Parasites were identified in 312
      (4.78%) cases. Giardia intestinalis, Ascaris lumbricoides and Entamoeba
      histolytica were identified in 2.27%, 1.15% and 0.64% cases respectively.
      CONCLUSION: Analysis of recent nationwide studies revealed V. cholerae was the
      most common bacterial/parasitic agent of diarrhea across all populations, being
      followed by diarrheagenic E. coli and Giardia intestinalis. Periodic laboratory
      monitoring of antimicrobial susceptibility pattern is essential, as is
      formulation of effective antibiotic use policy.

PMID- 25954616
TI  - Surgical site infections due to rapidly growing mycobacteria in puducherry,
      India.
AB  - BACKGROUND: Rapidly growing Mycobacteria are increasingly recognized, nowadays as
      an important pathogen that can cause wide range of clinical syndromes in humans.
      We herein describe unrelated cases of surgical site infection caused by Rapidly
      growing Mycobacteria (RGM), seen during a period of 12 months. MATERIALS AND
      METHODS: Nineteen patients underwent operations by different surgical teams
      located in diverse sections of Tamil Nadu, Pondicherry, Karnataka, India. All
      patients presented with painful, draining subcutaneous nodules at the infection
      sites. Purulent material specimens were sent to the microbiology laboratory. Gram
      stain and Ziehl-Neelsen staining methods were used for direct examination.
      Culture media included blood agar, chocolate agar, MacConkey agar, Sabourauds
      agar and Lowenstein-Jensen medium for Mycobacteria. Isolated microorganisms were
      identified and further tested for antimicrobial susceptibility by standard
      microbiologic procedures. RESULTS: Mycobacterium fortuitum and M.chelonae were
      isolated from the purulent drainage obtained from wounds by routine
      microbiological techniques from all the specimens. All isolates analyzed for
      antimicrobial susceptibility pattern were sensitive to clarithromycin, linezolid
      and amikacin but were variable to ciprofloxacin, rifampicin and tobramycin.
      CONCLUSION: Our case series highlights that a high level of clinical suspicion
      should be maintained for patients presenting with protracted soft tissue lesions
      with a history of trauma or surgery as these infections not only cause physical
      but also emotional distress that affects both the patients and the surgeon.

PMID- 25954617
TI  - Study of biofilm in bacteria from water pipelines.
AB  - CONTEXT: A biofilm is a layer of microorganisms contained in a matrix (slime
      layer), which forms on surfaces in contact with water. Their presence in drinking
      water pipe networks can be responsible for a wide range of water quality and
      operational problems. AIM: To identify the bacterial isolates, obtained from
      water pipelines of kitchens, to evaluate the water quality & to study the biofilm
      producing capacity of the bacterial isolates from various sources. SETTINGS AND
      DESIGN: A prospective study using water samples from aqua guard & pipelines to
      kitchens of S.C.B Medical College hostels. MATERIALS AND METHODS: Standard
      biochemical procedures for bacterial identification, multiple tube culture & MPN
      count to evaluate water quality & tissue culture plate (TCP) method for biofilm
      detection was followed. STATISTICAL ANALYSIS: STATA software version 9.2 from
      STATA Corporation, College station road, 90 Houston, Texas was used for
      statistical analysis. RESULTS: One hundred eighty seven isolates were obtained
      from 45 water samples cultured. The isolates were Acinetobacter spp. (44),
      Pseudomonas spp.(41), Klebsiella spp.(36) & others . Biofilm was detected in (37)
      19.78 % of the isolates (95% CI 30.08% -43.92%) including Acinetobacter spp.-10,
      Klebsiella spp. - 9, Pseudomonas spp. - 9, & others, majority (34) of which were
      from kitchen pipelines. CONCLUSION: Water from pipeline sources was
      unsatisfactory for consumption as the MPN counts were > 10. Most of the biofilm
      producers were gram negative bacilli & Pseudomonas & Acinetobacter spp. were
      strong (4+) biofilm producers.

PMID- 25954618
TI  - Comparative Study in Early Neonates with Septicemia by Blood Culture, Staining
      Techniques and C - Reactive Protein (CRP).
AB  - AIM: The aim of this study was to compare and evaluate the pathogenic bacteria in
      neo-natal septicemia by using various diagnostic techniques. SETTING AND DESIGN:
      Our study was designed to evaluate a feasible method to diagnose neonatal
      septicemia even at primary health centre level. MATERIALS AND METHODS: Blood
      samples were collected aseptically from 70 neonates. The specimens were
      inoculated into brain heart infusion broth and subcultures were performed with
      specific media. Antibiotic sensitivity pattern of isolates was studied by
      Modified Kirby Bauer Disc diffusion technique and differentiate the isolates by
      staining methods. C-reactive protein (CRP) was evaluated by using standard kit
      method. RESULTS: Out of 70 cases of childhood septicemia of age group 1-30 days,
      37 had positive CRP, 36 were positive for BCS and blood culture was positive only
      in 41 cases, where predominant organism being Klebsiella species (n=28, 68.29%)
      followed by Escherichia coli (n=4, 9.76%), Pseudomonas aeruginosa (n=3,7.31%),
      Proteus mirabilis (n=2,4.88%) and Coagulase negative staphylococcus (n=4,9.76%).
      CONCLUSION: Our findings suggest that Klebsiella species as an important cause of
      neonatal septicemia. The isolated organisms were found to be highly sensitive to
      cefatoxime and amikacin. Hence, these antibiotics can be considered as the first
      drug of choice for neonatal septicemia.

PMID- 25954619
TI  - Kodameae ohmeri - An Emerging Yeast: Two Cases and Literature Review.
AB  - Kodameae ohmeri is an emerging pathogen in various types of infections. Most
      infections are seen in patients with compromised immunity like cancer patients.
      Few cases of neonatal infections due to K. ohmeri have been reported earlier in
      premature neonates with fatal outcomes. We report two cases of fungemia; the
      first case was a patient with hematological malignancy, who complained of fever
      spikes and grew K. ohmeri in blood despite prophylactic voriconazole therapy. The
      second case was in a mature neonate, who developed respiratory distress and
      features of sepsis two days after birth, multiple blood cultures were positive
      for K. ohmeri. Both the patients responded well to Amphotericin B. Repeat blood
      cultures were sterile and patients were discharged. K. ohmeri is an unusual and
      emerging fungal pathogen of late an increasing number of cases of fungemia,
      funguria, endocarditis, peritonitis and wound infections due to the same are
      being reported. Some occur in immunocompromised patients and some inapparently
      immunocompetent patients, neonates with an inclination for preterm babies. We
      report two case of fungemia, one with lymphoma and the second in a neonate. 

PMID- 25954620
TI  - Teixobactin: a novel antibiotic in treatment of gram positive bacterial
      infections.

PMID- 25954621
TI  - Is scrub typhus a cause of febrile illness among paediatric population of delhi?

PMID- 25954622
TI  - A comparison of manual and automated methods of quantitation of
      oestrogen/progesterone receptor expression in breast carcinoma.
AB  - BACKGROUND: Oestrogen/progesterone receptor expression in breast carcinoma is
      associated with good response to hormonal therapy and overall better prognosis.
      The predictive and prognostic capabilities of these receptors are enhanced by
      quantitation of immunoreaction. There are several manual and automated methods
      for this purpose. Whether they yield comparable results that can be used
      interchangeably is not yet clear. AIM: To compare the manual methods (H-score and
      Allred score) with automated methods (Immunoratio) for quantifying
      immunohistochemical (IHC) reaction for ER/PR in breast carcinoma. MATERIALS AND
      METHODS: Samples from established cases of breast carcinoma were processed and
      stained by immunohistochemical methods to demonstrate oestrogen receptor (ER) and
      progesterone receptor (PR). Receptor expression was quantified by manual methods
      (H-score, modified H-score and Allred score) and automated methods (basic and
      advanced Immunoratio). In modified H score, the intensity of reaction was
      assessed by measurement of mean grey value {H (MGV)} or optical density {H (DC
      OD)} of deconvoluted image. The manual counting was done with cell counter plugin
      of Image-J (NIH). The scores were compared and Pearson's correlation coefficient
      was determined. RESULTS: Both manual and automated methods produced results that
      were comparable. There was a statistically significant positive correlation among
      all methods (p<0.02). The strongest correlation was observed between advanced
      immunoratio and H (DC-OD) (p=<0.001). Basic immunoratio appeared to be less
      reliable than the other methods. Staining intensity measurements by various
      methods did not significantly affect correlation. However, intensity measurements
      by optical density resulted in lower H-scores but led to more reliable detection
      of negative immunoreaction. CONCLUSION: Both manual and automated methods of
      quantitation are comparable. Advanced immunoratio is a reliable alternative to
      manual methods. Cell Counter plugin is a useful tool for manual counting and
      quantitation.

PMID- 25954623
TI  - HER 2 Expression in Gastric and Gastro-esophageal Junction (GEJ) Adenocarcinomas.
AB  - INTRODUCTION: Gastric cancer is one of the leading causes of cancer mortality in
      the world/India with majority being diagnosed at an advanced stage. Various
      chemotherapeutic regimens have modestly improved overall survival leading to
      quest for novel therapeutic agents. Overexpression of HER2 in many gastric
      cancers has lead to the advent of targeted therapy with anti HER2 antibody like
      Trastusumab which has improved the overall survival. MATERIALS AND METHODS: Sixty
      cases of gastric adenocarcinomas (44 biopsies and 16 gastrectomies) over the past
      five years ( June 2009 to June 2014),were included in the study. Diagnosis was
      confirmed by review of slides and IHC with anti HER2 antibodies was performed
      using Dako Real Envision Detection system and scoring was done by Hoffmann et
      al., scoring system. RESULTS: Of the 60 cases, majority were males (60%),with a
      mean age of 65.65 yrs. Tumours in antrum (76.7%) formed the major bulk. HER2
      expression was observed in 26.7% of Tumours, predominantly in males (p=0.006) and
      intestinal type (p= 0.054). HER2 expression correlated with Tumour grade
      (moderately differentiated and well differentiated, p= 0.042). Tumours of gastro
      esophageal junction (GEJ) showed HER2 expression in 45.5% as opposed to 22.4% in
      gastric location. Poorly differentiated and diffuse type of adenocarcinomas did
      not express HER2. Two of three Tumours from patients in the age group 31-40 y
      expressed HER2. CONCLUSION: Male gender, intestinal-type and moderately
      differentiated gastric cancers may be the ones that can be targeted for therapy
      using Herceptin. Though trastusumab is approved for advanced gastric and GEJ
      cancers, it's role in adjuvant / neo-adjuvant setting in early stages needs to be
      evaluated with newer agents like Pertuzumab, Bevacizumab, especially in young
      patients.

PMID- 25954624
TI  - Cervicitis: How Often Is It Non-specific!
AB  - BACKGROUND: Uterine cervix is most often reported as 'non specific cervicitis'.
      It is an effort to encourage specific reporting and thereby avoiding the term
      'non specific' to a possible extent. MATERIALS AND METHODS: The study is carried
      out on 613 specimens of uterine cervix received at Department of Pathology,
      Aarupadai Veedu Medical College, Pondicherry, between 1(st) January 2010 to
      31(st) December 2012. Histopathology slides of all the cases were studied for the
      presence of specific features of various inflammatory lesions. RESULTS are
      expressed in percentage. RESULTS: Chronic nonspecific cervicitis was the
      commonest inflammatory lesion constituting 89.23% of the cases. Other
      inflammatory lesions were follicular cervicitis in 6.85%, chronic cervicitis with
      koilocytosis in 3.75% and only one case (0.16%) of tuberculosis was observed.
      CONCLUSION: Importance of these benign lesions of the uterine cervix lies in the
      fact that some of them like Chlamydia, Papilloma infection have specific
      treatment and some of them form differential diagnosis for malignant lesions and
      some progress to malignancy.

PMID- 25954625
TI  - Study of Metastasis in Lymphnode Biopsies with Special Reference to
      Immunohistochemistry (IHC) in Metastatic Breast Carcinoma.
AB  - CONTEXT: Lymph nodes are the most common site of metastatic malignancy, and
      sometimes constitute the first clinical manifestation of the disease. Metastases
      are tumour implants discontinuous with the primary tumour. The characterization
      of a neoplasm as primary or metastatic has always troubled surgical pathologists.
      AIM: To study distribution of lymph node metastasis in North Karnataka region
      based on age, sex, location and morphological features, and to explore the
      utility of special stains and immunohistochemistry (IHC) in its diagnosis.
      MATERIALS AND METHODS: The present study includes 228 cases of lymph node
      metastasis studied over a 10-year period (July 2004- June 2014). The H&E slides
      were reviewed, special stains and IHC done wherever necessary. RESULTS: Out of
      228 cases, maximum were seen between 2012-2014 (79 cases; 34.65%). Age ranged
      from 16-85y (Mean- 47.02) with female predominance (Male:Female 1:2.55.). In 186
      cases (81.58%) more than one lymph node received, while in majority of cases
      (35.09%) size of the lymph node was between 1-2cms. Most common site of
      metastasis was axillary lymph nodes (33.77%) followed by cervical (22.50%) and
      pelvic (9.64%). Primary was mainly from breast carcinoma (33.77%) followed by
      squamous cell carcinoma (31.57%) and adenocarcinoma (10.52%). IHC in 60 cases
      with breast carcinoma metastasis showed ER positivity in 45.00%, PR positivity in
      41.67% and HER2/neu positivity in 38.33%. CONCLUSION: Identification of the size,
      number, microscopic type and possible primary site of metastasis is important
      prognostically especially in breast carcinoma. This study elaborates the pattern
      of distribution of lymph node metastasis in North Karnataka region with IHC as an
      aid to diagnosis.

PMID- 25954626
TI  - Pseudoactinomycotic Radiate Granules (PAMRAGs)- An Unusual Differential Diagnosis
      for Ovarian Neoplasm; A Diagnostic Dilemma.
AB  - Pseudoactinomycotic radiate granules (PAMRAGs) are rarely detected lesions in
      ovary. Endometrium is the usual site and a detailed search of literature yielded
      only two cases in the ovary. PAMRAGs must be differentiated from actinomycotic
      granules which are also strongly associated with the use of intrauterine
      contraceptive devices (IUCDs). In cases of suppurative oophoritis due to
      actinomycosis, a proper diagnosis and culture confirmation is mandatory to avoid
      further complications. This case is reported due to its rarity, unusual clinical
      presentation and to highlight the importance of special stains in cases of
      tuboovarian abscess, where PAMRAGs may cause diagnostic dilemma. Our patient was
      a 50 yr old female admitted with clinical diagnosis of malignant ovarian tumour.
      After preoperative work up, panhysterectomy, infracolic omentectomy and excision
      biopsy of the right inguinal lymph node were done. Peroperatively the right ovary
      was enlarged and adherent to the fallopian tube and pelvic wall. Gross
      examination revealed a right tuboovarian mass with yellowish areas of necrosis
      and fibrosis. Histology showed a suppurative granulomatous lesion with spherical
      granules having club like peripheral projections. A panel of special stains (GMS,
      GRAMs and AFB) done were negative. Thus, we ruled out actinomycosis and gave a
      diagnosis of PAMRAG. 

PMID- 25954627
TI  - Solitary fibrous tumour of lacrimal gland: a rare entity.
AB  - Solitary fibrous tumour (SFT) is a rare spindle cell tumour of mesenchymal origin
      most commonly encountered in pleura. It can affect the orbital region but SFT of
      lacrimal gland is rare. We hereby report of a SFT of lacrimal gland in a 50-year
      old male presenting with slow growing swelling in left superolateral orbital
      region. The preliminary fine needle aspiration cytology (FNAC) could not reveal
      any definite diagnosis. Excision biopsy and immunohistochemistry (IHC) confirmed
      the diagnosis. Therefore, clinician and pathologist should be aware of this
      entity and biopsy along with IHC is required to rule out other entities which can
      mimic it clinically and histopathologically. 

PMID- 25954628
TI  - Oncocytic lipoadenoma of submandibular gland: a case report.
AB  - Lipomatous tumours of salivary glands are very uncommonly diagnosed and reported
      tumours. Majority of these tumours present as painless masses which grow slowly
      over many years. On the histological grounds, they can be subclassified into
      "monophasic" (lipoma component only) and "biphasic" (lipoma component+epithelial
      component) tumours. A handful of biphasic tumours contain oncocytic component and
      they have been omitted from the WHO classification of salivary gland tumours so
      far and this has remained a matter of persistent confusion and controversy over
      many years. Other rare variants of monophasic tumours include fibrolipoma,
      sialolipoma, angiolipoma, sialadenosis and very rarely a liposarcoma can also
      occur in salivary glands. Pre-operative imaging can help in picking up the fatty
      component of the tumours and guide in accurate classification. FNAC may not be
      accurate in diagnosis of these tumours. We report a case of 45-year-old gentleman
      presenting with submandibular gland swelling for which submandibular gland
      excision was done. A final diagnosis of oncocytic lipoadenoma was made. We
      present this rare entity to add to the few cases reported to date and hence, to
      increase recognisation and understanding of these rare tumours, which may help in
      establishing a reproducible subclassification. We have discussed the pathological
      aspects with review of literature of this very rare entity. 

PMID- 25954629
TI  - Analysis of Out Door Patients' Prescriptions According to World Health
      Organization (WHO) Prescribing Indicators Among Private Hospitals in Western
      India.
AB  - BACKGROUND: Prescription is document through which doctor, patient and pharmacist
      are communicated. Many a times if these documents are not properly written or
      misinterpreted it can affect management of patients. WHO established prescribing
      indicators to analyse prescription and promoted rational use of drugs and better
      management of patients. AIM: To study the prescription pattern according to WHO
      prescribing indicators among private hospitals. SETTINGS AND DESIGN: The
      observational, prospective study carried out at different private hospitals at
      metro city in Western India to study the prescription pattern among private
      hospital. MATERIALS AND METHODS: Study was conducted at different private
      hospitals of metro city. A total of 250 prescriptions of outdoor patients from
      various departments of private hospitals were collected for a period of three
      months (August to October) 2012 and evaluated. STATISTICAL ANALYSIS: The study
      was analysed using Z-test. RESULTS: Patient details like age and gender was not
      written in all (100%) prescriptions. It was noticed that dose, direction of drug
      and duration of treatment was not completely written in 90%, 74% and 80% of
      prescriptions respectively. Abbreviations were used in all (100%) prescriptions.
      Doctor's medical registration number was mentioned in 0% prescriptions. Total 869
      drugs were prescribed in 250 prescriptions. Average number of drug prescribed was
      3.38+/-1.79 (Mean+/-SD). It was reported that Group II (3 to 4 encoutner) was
      significantly higher as compared to Group I (less than or equal to 2 encoutner)
      and Group III( more than four encounter). It was significantly (p<0.05)
      prescribed brand name prescriptions (93.33%) as compared to generic name
      prescriptions (6.7%). Percentage of encounter with antibiotics and injections was
      54% and 18% respectively. Approximately 70% drugs were prescribed according to
      Essential Medicine List (EML) of State. Antibiotics accounted 30% of prescribed
      drugs which was significantly higher as compared to other group of prescribed
      drugs. CONCLUSION: Our study revealed that prescription errors were most commonly
      observed at private hospitals and antibiotics was commonly prescribed in private
      sector. Therefore, strict policy to good prescribing practice and strict
      antibiotic policy in outdoor patients are required to promote rational use of
      drugs.

PMID- 25954630
TI  - A prospective, comparative study of the occurrence and severity of constipation
      with darifenacin and trospium in overactive bladder.
AB  - INTRODUCTION: Darifenacin and trospium are the commonly used antimuscarinics in
      the management of overactive bladder (OAB). Constipation is the second most
      common treatment related side-effect. Though its incidence with the above two
      medications is known, data on their comparative severity and impact on patient's
      well-being is lacking. MATERIALS AND METHODS: Sixty subjects with OAB included in
      the study were randomized in 1:1 fashion to receive either darifenacin 7.5 mg OD
      or trospium extended release 60 mg OD. Treatment response was monitored using
      overactive bladder symptom score (OABSS). The severity of constipation was
      assessed using McMillan & Williams Constipation assessment scale (CAS), Bristol
      stool form scale and Knowles-Eccersley-Scott-Symptom (KESS) questionnaire score
      administered at baseline, 2 and 4 weeks of treatment. RESULTS: OABSS improved
      significantly, -5.80 +/- 3.99 (p = 0.0005) and -5.27 +/- 2.98 (p = 0.0005) in
      darifenacin and trospium groups respectively. However, the difference between the
      two groups was not significant either at 2 weeks (p = 0.952) or 4 weeks (p =
      0.654) of treatment. A significant decrease in stool consistency was noted with
      darifenacin treatment (p < 0.05), but the same was not seen with trospium (p =
      0.076). There was no significant difference in scores of KESS questionnaire
      between baseline, 2 weeks and 4 weeks, both within the group and between the
      groups (p > 0.05). McMillan & Williams CAS scores increased at week 2 and week 4,
      in comparison with baseline scores in both darifenacin and trospium treated
      patients, however, the difference between the two groups was not statistically
      significant (p > 0.05). CONCLUSION: Darifenacin and trospium are equally
      efficacious and comparable in tolerability in terms of constipation severity and
      its impact on patient well-being.

PMID- 25954631
TI  - A comparative study of the clinical efficacy and safety of Lorazepam and
      chlordiazepoxide in alcohol dependence syndrome.
AB  - BACKGROUND: Currently, benzodiazepines are the preferred drugs in the management
      of alcohol withdrawal symptoms. Chlordiazepoxide and diazepam, the most
      frequently used drugs have a long duration of action and are converted to active
      metabolites in the liver, while lorazepam is shorter acting, with no active
      metabolites. OBJECTIVE: To compare and evaluate the safety and efficacy of
      lorazepam and chlordiazepoxide in patients with alcohol dependence syndrome with
      symptoms of alcohol withdrawal. MATERIALS AND METHODS: This was a prospective,
      randomized, double-blind, study carried out at a teaching hospital in Bangalore.
      Sixty patients aged >=18 y with alcohol dependence syndrome with mild-to-moderate
      withdrawal symptoms were allocated at a ratio of 1:1 to either lorazepam or
      chlordiazepoxide, by means of a computer-generated randomization chart. Thirty
      patients each were started with lorazepam tablets 8 mg/day and chlordiazepoxide
      80 mg/day. For both treatment groups, the dose was tapered and at the end of 8
      days, the patients were drug-free. The severity of alcohol dependence was
      assessed using the Severity of Alcohol Dependence Questionnaire (SADQ). The CIWA
      Ar was used for quantification of withdrawal symptoms. Liver function tests were
      performed at baseline and at the end of the study. RESULTS: Of the 60 patients
      included in the study, 15 patients each had mild and moderate withdrawal symptoms
      in the chlordiazepoxide group and 17 and 13 patients respectively in the
      lorazepam group, based on the SADQ score. At baseline, the mean CIWA-Ar scores
      were similar in both the treatment groups: 24.77+/-5.98 in the chlordiazepoxide
      group and 24.90+/-6.12 in the lorazepam group. There was a significant intragroup
      decrease in the CIWA-Ar scores measured from baseline to the end of 8 days
      (p<0.0001) and 12 days (p<0.0001) in both treatment groups; however, there was no
      significant difference between the two groups. There was no significant
      difference observed in the liver function tests done at baseline and at the end
      of study period. CONCLUSION: Lorazepam is noninferior to chlordiazepoxide in
      reducing alcohol withdrawal symptoms.

PMID- 25954632
TI  - Association of parental origin with clinical profile in klinefelter syndrome.
AB  - INTRODUCTION: Several genomic imprinting mechanisms have been postulated to
      report the parent-of-origin in Klinefelter syndrome. It was stated in the
      literature, parental origin has an effect on behavioral phenotype of Klinefelter
      individuals, but the association of the same on clinical profile was less
      reported. The detailed clinical phenotype when studied with the known origin of
      extra X may possibly explain the imprinting effect that may be helpful to derive
      diagnostic criteria in the syndrome. In the present study, we investigated the
      parental-of-origin of extra X chromosome in Klinefelter syndrome probands with an
      aim to report the association between the phenotype with that of its karyotype
      and the parental origin of supernumerary X. MATERIALS AND METHODS: Seventy two
      probands that were referred to division of Human Genetics, St.John's Medical
      College, Bangalore with variable complaints and phenotypic features were
      diagnosed with informed consent as Klinefelter syndrome with a confirmed
      karyotype. The Karyotype was prepared by peripheral lymphocyte culture and GTG
      banding method. The parental origin was studied in 9 families of Klinefelter
      probands with standard protocol for GENE SCAN using X-chromosome specific Short
      Tandem Repeat markers. The outcome was analyzed to determine the parental origin
      by GENE MAPPER. STATISTICAL ANALYSIS: STATISTICAL ANALYSIS was conducted to
      ascertain the significance of parental origin of supernumerary X with the
      phenotypic profile with confirmed karyotype. RESULTS: Seven of nine probands had
      47, XXY karyotype and 2 were mosaic with 47,XXY/46,XY karyotype. Five probands
      had their supernumerary X from maternal side and four were paternally derived.
      Sixteen features as framed proforma were tabulated against the originated X in
      Klinefelter probands. 55.56% of Klinefelter stigmata were seen in prob and who
      had maternally derived X and the rest were with paternal X. CONCLUSION: The
      findings of the present study points on parent-of-origin effect on clinical
      profile and indicate that the imprinted X chromosome genes show differential
      effect general and systemic traits.

PMID- 25954633
TI  - A comprehensive review on clinical applications of comet assay.
AB  - Increased levels of DNA damage and ineffective repair mechanisms are the
      underlying bio-molecular events in the pathogenesis of most of the life
      threatening diseases like cancer and degenerative diseases. The sources of DNA
      damage can be either exogenous or endogenous in origin. Imbalance between the
      oxidants and antioxidants resulting in increased reactive oxygen species mostly
      accounts for the endogenously derived attacks on DNA. Among the various methods
      employed in the estimation of DNA damage, alkaline comet assay is proven to be a
      relatively simple and versatile tool in the assessment of DNA damage and also in
      determining the efficacy of DNA repair mechanism. The aim of this article is to
      review the application of comet assay in the field of medicine towards human
      biomonitoring, understanding the pathogenesis of cancer and progression of
      chronic and degenerative diseases, prediction of tumour radio & chemosensitivity
      and in male infertility. A standardized protocol and analysis system of various
      variants of comet assay in different types of cells, across the labs will be of
      useful and reliable clinical tool in the field of Medicine for the estimation of
      levels of DNA damage and repair mechanisms. 

PMID- 25954634
TI  - Course of Near-hanging Victims Succumbed to Death: A Seven Year Study.
AB  - INTRODUCTION: Near hanging refers to victims who survive a hanging injury
      following attempted hanging, long enough to reach hospital. Delayed deaths in
      near hanging patients are mostly due to complication of hanging. The purpose of
      this study was to evaluate the demographics, mortality patterns and cause of
      delayed deaths in near hanging victims. MATERIALS AND METHODS: In this study
      autopsy files over a seven year period from 2007 to 2013 were reviewed, and data
      of near hanging deaths (attempted hanging cases who succumbed to death and
      subjected for medicolegal autopsy) was extracted. Records of 14,000 autopsies was
      reviewed, and 10 deceased having died delayed deaths after near hanging episode
      were identified. In each case, the patients' details, including gender, age, type
      of suspension, type of ligature material used for hanging and subsequent hanging
      mark produced were reviewed using autopsy reports and photographs taken during
      autopsy. RESULTS: Demographic and pathological aspects of the each case discussed
      to throw light on autopsy findings in victims who died following near hanging.
      Complete suspension was present in 3 cases, while partial suspension was present
      in 7 cases. Survivals in delayed death after near hanging episode have ranged
      from 9 h to 72 d. Hypoxic encephalopathy was the most common cause of death,
      followed by pneumonia. CONCLUSION: Most of the near hanging patients did succumb
      to hypoxic encephalopathy; however, consolidation of lungs (pneumonia) was the
      next common cause of death reflecting need for aggressive oxygen therapy and
      selective resuscitation should be performed in all such cases.

PMID- 25954635
TI  - Lorazepam: a weapon of offence.
AB  - The use of knock out drugs for perpetuation of crime has significantly increased
      in recent years. These drug facilitated crimes mainly involve robbery and sexual
      offences. Most of the drugs employed for these purposes affect the nervous system
      and bring a state of incapacitation and amnesia. The miscreants exploit these
      properties of drugs to commit such crimes. The unsuspecting travellers on public
      transport vehicles and women in disco parties are most vulnerable to such crimes.
      The unrestricted and unregulated sale of prescription drugs and general ignorance
      of such incidents is a challenge that needs to be addressed promptly. 

PMID- 25954636
TI  - How can Doctors Improve their Communication Skills?
AB  - The process of curing a patient requires a holistic approach which involves
      considerations beyond treating a disease. It warrants several skills in a doctor
      along with technical expertise. Studies have shown that good communication skill
      in a doctor improve patient's compliance and overall satisfaction. There are
      certain basic principles of practicing good communication. Patient listening,
      empathy, and paying attention to the paraverbal and non verbal components of the
      communication are the important ones that are frequently neglected. Proper
      information about the nature, course and prognosis of the disease is important.
      Besides, patients and attendants should always be explained about the necessity
      and yield of expensive investigations and risks/benefits involved in invasive
      procedures. One should be extremely cautious while managing difficult encounters
      and breaking bad news. Formal training of the doctors in improving communication
      skills is necessary and has proven to improve overall outcome. The authors
      recommend inclusion of formal training in communication skills in medical
      curriculum and training of practising doctors in the form of CMEs and CPEs. 

PMID- 25954637
TI  - A Randomized Double-blind Controlled Trial of Lactobacillus acidophilus Plus
      Bifidobacterium bifidum versus Placebo in Patients with Hypercholesterolemia.
AB  - BACKGROUND: Hypercholesterolemia is a major risk factor for cardiovascular
      disease. Not all patients respond well to traditional cholesterol lowering
      medications. Probiotics have been evaluated for their cholesterol-lowering
      effects in humans with variable results. This study was performed to evaluate the
      efficacy of two probiotics in lowering the serum cholesterol of
      hypercholesterolemic patients. MATERIALS AND METHODS: A randomized double-blind
      controlled trial was conducted comparing placebo to Lactobacillus acidophilus
      plus Bifidobacterium bifidum in patients diagnosed with hypercholesterolemia.
      Placebo or probiotic capsules were taken three times daily for six weeks. Pre-
      and post-treatment total cholesterol (TC), HDL-cholesterol (HDL-C), LDL
      cholesterol (LDL-C) and triglyceride (TG) levels and demographic parameters of
      the two groups were compared. From a total of 70 participants, 64 completed the
      assigned treatment (31 in probiotics group and 33 in the control group).The two
      treatment groups were matched for age, sex, weight, height, BMI, waist and hip
      circumferences, and blood pressure. RESULTS: Baseline evaluation revealed no
      difference between the probiotics group and control group levels of TC, HDL-C,
      LDL-C and TG. TC levels in the probiotics group decreased during treatment (237.2
      vs. 212.7 mg/dL, p<0.05). TC and LDL-C levels in the control group increased
      significantly from their baseline levels during treatment. TC (212.7 vs 252.8
      mg/dL, p<0.001), HDL-C (52.0 vs 59.1 mg/dL, p=0.04) and LDL-C (153.9 vs 182.1
      mg/dL, p<0.01) levels in the probiotics group were significantly lower at the end
      of treatment than the corresponding levels in the control group. CONCLUSION: A
      combination of Lactobacillus acidophilus and Bifidobacterium bifidum decreased
      serum total cholesterol, LDL-cholesterol and HDL-cholesterol levels in
      hypercholesterolemic patients over a six week period. There was no effect on
      serum triglyceride or fasting blood glucose levels.

PMID- 25954638
TI  - Awareness and attitude regarding breastfeeding and immunization practices among
      primigravida attending a tertiary care hospital in southern India.
AB  - INTRODUCTION: Infant mortality rate (IMR) is considered as one of the most
      sensitive indicators of health status of a community. Infant mortality figures in
      India are very high and the two important causes which contributes maximum to the
      IMR is inadequate breastfeeding and immunization. The major cause of death among
      under five children in India is neonatal sepsis, diarrhea and pneumonia and
      breast milk is protective against all the three diseases. Immunization along with
      breastfeeding reduces a significant number of infant and maternal mortality.
      Disease like neonatal tetanus is rampant in our country and it can be prevented
      by vaccination of the women during pregnancy. This study tries to find out the
      awareness and attitude among the primigravida females regarding breastfeeding and
      immunization. MATERIALS AND METHODS: This facility based cross-sectional study
      was conducted among 186 primigravida who came to the hospital for delivery and
      antenatal check-up during March 2014 in three associated teaching hospitals of
      Kasturba Medical College, Mangalore, which is situated in coastal South India.
      Approval was obtained from the Institutional Ethics Committee (IEC) of KMC
      (Manipal University), Mangalore, India. A pre tested, semi structured
      questionnaire was used as the data collecting tool. RESULTS: Majority (n=163,
      87.6%) were Hindus followed by Muslims (n=16, 3.2%). Nearly half of the
      participants (n=92, 49.5%) were in the 21-25 y age group, 54.8% participants were
      not aware of correct position of baby during feeding and 10.8% (n=20) believed
      that immunization should be stopped if it showed side effects. CONCLUSION:
      Breastfeeding and Immunization is an effective way of reducing child and maternal
      mortality. The results from our study showed that many participants had lacunae
      in knowledge and attitude and adequate health education should be given to the
      pregnant women.

PMID- 25954639
TI  - Hearing screening in a tertiary care hospital in India.
AB  - INTRODUCTION: To study the incidence of hearing loss among children and to
      determine and confirm the distribution of common risk factors in children with
      hearing loss presenting at a tertiary care hospital in India. MATERIALS AND
      METHODS: Babies underwent hearing screening using Transient Evoked Otoacoustic
      Emission (TEOAE) and Automated Auditory Brainstem Response (AABR) from November
      2009 to September 2011. It was a cross-sectional study carried out at our
      institute involving 500 babies (<=2 y). To identify the high risk babies, Joint
      Committee on Infant Hearing (2007) High risk registry was used. RESULTS: In our
      study 110 (22%) babies belonged to high risk category and 11(2.2%) of total
      screened babies had significant hearing loss. Total number of babies who passed
      the initial screening with TEOAE was 284 (56.8%). On diagnostic AABR screening of
      TEOAE REFERRED babies, the babies with no risk factor showed normal AABR tracings
      whereas from among those with one or multiple risk factors (110 babies), 11(10%)
      showed different levels of hearing impairment. Hearing loss was highly associated
      with Neonatal Intensive Care Unit (NICU) admission i.e. 8/11(72.7%), followed by
      Low Birth Weight (LBW) and hypoxia (6/11 i.e. 54.5% each). CONCLUSION: Hearing
      loss is more common in those babies with risk factors (majority being NICU
      admission, LBW and hypoxia). OAE and ABR screening of infants at risk for
      significant hearing loss is a clinically efficient and cost effective approach
      for early detection of significant hearing loss.

PMID- 25954640
TI  - Otorhinolaryngological Manifestations among HIV Positive Children in Coastal
      Karnataka.
AB  - INTRODUCTION: With changed clinical profile of HIV related diseases, our study
      attempted to analyse otorhinolaryngological manifestations in HIV positive
      children coming to ART centre of a tertiary referral in South India. MATERIALS
      AND METHODS: Records of 137 children registered at ART Centre, Government Wenlock
      Hospital, Kasturba Medical College, Mangalore from 2004 till 2010 were studied
      and data for this retrospective study was collected. RESULTS: Twenty three
      (16.8%) children developed otorhinolaryngological manifestations, which were
      upper respiratory tract infection (13.1%), oral candidiasis (1.4%), otitis media
      (1.4%) and parotitis (1%). With increasing WHO stage, the ENT manifestations
      increased (p<0.05) while CD4 count decreased (p>0.05), 35% and 44% cases with ENT
      manifestations had CD4 counts above 500 cells/mm3 and below 200 cells/mm3
      respectively (p>0.05). 24% children on HAART and 10.7% not on HAART developed ENT
      illnesses (p<0.05). CONCLUSION: With the current ART protocols, ENT
      manifestations are seen in 17% HIV positive children, most of which are
      aspecific.

PMID- 25954641
TI  - Chrysosporium: an uncommon fungus in chronic rhinosinusitis.
AB  - Chronic rhinosinusitis is one of the commonest health problem encountered in
      rhinology. Of these allergic fungal rhinosinusitis forms a significant group of
      patients. Patients commonly present with typical symptoms of sinusitis and the
      diagnosis is often made after imaging and/or intraoperatively. We report a rare
      case of allergic fungal sinusitis (AFS) caused by Chrysosporium species in a 70
      year-old male with no co-morbidities. The fungus was isolated from allergic mucin
      collected from the sinuses. Therapy with intravenous Voriconazole was given
      leading to good relief for the patient, and no recurrences have occurred till
      date. Infections caused by Chrysosporium species are very rare, and is very
      rarely been reported to cause sinusitis in humans. 

PMID- 25954642
TI  - T-cell lymphoma of the oral cavity: case report.
AB  - Lymphomas are heterogenous malignancies of the lymphatic system characterized by
      lymphoid cell proliferation. They can broadly be divided into Hodgkin's lymphoma
      (HL) and non- Hodgkin's lymphoma (NHL). NHL can originate from B, T, or natural
      killer (NK) lymphocytes. Extra-nodal presentation of T-cell NHL is extremely
      rare, and is often seen in immunocompromised individuals. Here, we report a rare
      case of T-cell lymphoma of the oral cavity in an immune-competent patient. The
      patient was diagnosed to have T-cell NHL on the basis of biopsy and
      immunohistochemistry, and was referred to oncology department for chemotherapy
      for definite treatment. 

PMID- 25954643
TI  - Foveal and Macular Thickness Evaluation by Spectral OCT SLO and Its Relation with
      Axial Length in Various Degree of Myopia.
AB  - PURPOSE: To evaluate the foveal and macular thickness in various degrees of
      myopia and its association with axial length in low, moderate and high degrees of
      myopia. DESIGN: A cross-sectional study was done in the Department of
      Ophthalmology, MGMCRI, Pondicherry, India. MATERIALS AND METHODS: One hundred and
      twenty five eyes eyes of 64 myopic subjects between the age group of 20-40 who
      fulfilled the inclusion criteria were selected and complete ophthalmic
      examination was done. Cycloplegic refraction was done and the subjects were
      categorized into low (n=43 eyes), moderate (n=43 eyes) and high (n=36) degrees of
      myopia. The foveal and macular thickness was assessed using spectral OCT- SLO and
      axial length was measured by A-scan biometry. RESULTS: The foveae minimum of high
      myopia (178 +/- 26.4 microns) was significantly thicker compared to moderate
      myopia (p= 0.028). There was no significant intergroup difference in the
      thickness significance of the outer and inner macular between mild, moderate and
      high degree of myopia. The mean axial length of high myopia (26.7+/-0.97mm) was
      significantly higher compared to moderate (24.6+/-0.81mm) and low myopia (23.5+/
      0.81mm) with a p-value of p = 0.001. There was a positive correlation of axial
      length with foveae minimum, fovea and superior inner macula in respect to myopia
      (p<0.05). CONCLUSION: The foveal and macular thickness in myopia is influenced by
      the axial length. Early detection of such changes in macular thickness by using
      OCT is helpful in understanding the mechanism and factors affecting the
      structural changes of myopic eyes. Also it implicates the importance of
      refractive error induced retinal macular changes while interpreting OCT.

PMID- 25954644
TI  - Inverse Bell's Phenomenon: Rare Ophthalmic Finding Following Ptosis Surgery.
AB  - Bell's phenomenon is protective reflex in which the globe is turned upwards and
      slightly outwards during the eyelid closure to avoid corneal exposure. In Inverse
      Bell's phenomenon, the eye moves downward instead of upward, this may be seen in
      the normal population, patients with Bell's palsy or following conjunctival
      scarring. We hereby present the unusual complication of transient inversion of
      Bell's phenomenon following extensive levator resection surgery performed for
      congenital ptosis. A 24-year-old male was undergone ptosis correction surgery. On
      postoperative day two, ocular examination revealed down rolling of eye ball
      during eyelid closure. It underwent spontaneous resolution within four weeks
      without any corneal complication. The patients were given frequent lubricating
      eye drops during this period and advised frequent follow-up for early diagnosis
      of corneal complication. Here we highlight an inverse Bell's phenomenon following
      levator resection surgery, its possible mechanism and risk of corneal
      complication. 

PMID- 25954645
TI  - Obstetric acute kidney injury; a three year experience at a medical college
      hospital in north karnataka, India.
AB  - INTRODUCTION: Acute kidney injury is a rare and sometimes fatal complication of
      pregnancy, the incidence of which has been declining worldwide, though still high
      in developing countries. There are recent observations of increasing incidence in
      some developed countries attributed to hypertensive disorders of pregnancy.
      MATERIALS AND METHODS: In this study, we have analysed the records of all
      patients referred to the dialysis unit of a medical college hospital in Karnataka
      for acute kidney injury related to pregnancy. AKIN (Acute Kidney Injury Network)
      criteria for the diagnosis of acute kidney injury were adapted. Age, parity,
      gestational age, causative factors for acute kidney injury, mode of delivery,
      access to antenatal care, operative procedures, blood component transfusions,
      number of haemodialysis, time for initiation of haemodialysis, duration of
      hospital stay and mortality were analysed by finding mean, standard deviation and
      standard error. RESULTS: Fifteen patients out of 21563 who delivered in our
      hospital developed acute kidney injury. These (n=15) were out of 149 patients of
      acute kidney injury of various aetiologies who underwent haemodialysis between
      2012 and 2014. Of these two were unregistered for antenatal care. Ten were
      multiparous, Eleven were from rural background, one had home delivery, six had
      vaginal delivery, seven had caesarean section and two had second trimester
      abortion. Placental abruption with intrauterine death was the commonest Cause in
      9 out of 15 cases. All had severe anaemia. Patients received a mean of 3.9 (SD+/-
      2.4) sessions of haemodialysis. Eleven patients recovered completely, two died
      and two left against medical advice. CONCLUSION: Obstetric acute kidney injury is
      associated with poor access to antenatal care, multiparity and rural background.
      Placental abruption is the commonest cause of obstetric acute kidney injury.
      Blood component transfusions, avoidance of nephrotoxic drugs and early initiation
      of haemodialysis are associated with better outcome.

PMID- 25954646
TI  - Prognosis of left ventricular systolic dysfunction in septic shock patients.
AB  - INTRODUCTION: The prognosis of myocardial dysfunction in critically ill patients
      with sepsis and its association with mortality is controversial. We aim to
      determine the significance of left ventricular systolic dysfunction in septic
      shock patients and their associated outcome. MATERIALS AND METHODS: A
      prospective, single center, observational study was carried out at an intensive
      care unit of a tertiary care hospital. A total of 66 patients diagnosed with
      septic shock were enrolled in the study from September 2010 to June 2012. The 2D
      echocardiography was performed for all the patients. Ejection fraction <50% was
      the diagnosing parameter for the patients with systolic dysfunction in septic
      shock. Acute Physiology and Chronic Health Evaluation III (APACHE III) score was
      calculated. RESULTS: The mean age of patients were found to be 53.71 +/- 16.76
      years. The mortality rate was found to be 48.48% and among them 43.75% patients
      had ejection fraction <50%. Non-survivors exhibited significantly lower mean
      blood pressure (74.19 +/- 10.28 versus 80.59 +/- 11.31; p = 0.008), lower
      ejection fraction (52.59 +/- 16.37 versus 62.56 +/- 8.31; p = 0.029) and higher
      APACHE III score (89.34 +/- 15.41 versus 70.65 +/- 13.27; p <0.001). The receiver
      operating characteristic curves APACHE III score (area under curve = 0.830) and
      ejection fraction (area under curve = 0.656) were used to predict the mortality
      in septic patients. CONCLUSION: Low ejection fraction, a marker to measure left
      ventricular systolic dysfunction is a predictor of mortality in septic shock
      patients. However, more research is needed to confirm the findings.

PMID- 25954647
TI  - Study on assessment of renal function in chronic liver disease.
AB  - INTRODUCTION: Renal dysfunction is common in chronic liver disease. The cause of
      this renal dysfunction is either multi-organ involvement in acute conditions or
      secondary to advanced liver disease. OBJECTIVES: The study was undertaken to
      assess the renal function in chronic liver diseases and find out the association
      of alteration of renal function with gradation of liver disease. (assessed by
      child-pugh criteria) and to find out the association of alteration of renal
      function among the cases of chronic liver disease of different aetiology.
      MATERIALS AND METHODS: This cross-sectional, observational study was undertaken
      in Department of General Medicine, Calcutta National Medical College & Hospital,
      Kolkata during March 2012 to July 2013 with 50 admitted patients of chronic liver
      disease after considering the exclusion criteria. The patients were interviewed
      with a pre-designed and pre-tested schedule, examined clinically, followed by
      some laboratory investigations relevant to diagnose the aetiology of chronic
      liver disease, and to assess the severity of liver and renal dysfunction. Data
      was analysed by standard statistical method. RESULTS: Eighty six percent of the
      patients were male and the mean age of study population was 43.58 y, 68% patients
      suffered from alcoholic liver disease, followed by 14% patients had chronic
      Hepatitis-B, 10% patients developed acute kidney injury, 20% had hepato renal
      syndrome and 14% had IgA deposition. The distribution of serum urea and
      creatinine across the categories of Child Pugh classification tested by Mann
      Whitney test and the distribution was statistically significant. CONCLUSION: The
      present study has found significant association between severity of liver
      dysfunction and certain parameters of renal dysfunction.

PMID- 25954648
TI  - Thyroid hormones and prolactin levels in infertile women in southern Nigeria.
AB  - INTRODUCTION: Human infertility is a complex global health problem. It has
      multiple social consequences which are especially profound for thyroid hormones
      in infertility with the aim of determining the degree of association of thyroid
      hormones with hyperprolactinemia in our population. MATERIALS AND METHODS: The
      serum levels of prolactin, T3, T4 and TSH were determined in 90
      hyperprolactinemic infertile women, 90 normoprolactinemic infertile women and 50
      fertile women. The hormones were assayed using Enzyme Linked Immunosorbent Assay
      kits. STATISTICAL ANALYSIS: Analysis of variance and Pearson's correlation were
      used to analyze the data, with the significant p-level set at 0.05. RESULTS: A
      significantly higher mean serum prolactin and TSH were observed among the
      infertile groups compared to the fertile controls (p<0.05). The mean serum T3 and
      T4 were significantly lower in the hyperprolactinemic infertile women compared to
      the fertile controls (p<0.05). The mean TSH and T3 of normoprolactinemic
      infertile women and controls were comparable (p>0.05). However, the mean T4 was
      significantly lower in normoprolactinemic infertile women compared to the fertile
      controls (p<0.05). In all the groups, TSH correlated inversely with T3 and T4,
      while T3 correlated positively with T4. It was only in the control group that
      prolactin correlated positively and significantly with TSH. CONCLUSION: It is
      therefore concluded that hyperprolactinemia with thyroid dysfunction may be a
      major contributory hormonal factor in infertility among infertile women and as
      such, estimation of prolactin, T3, T4 and TSH should be included in the workup
      for infertile women especially those with hyperprolactinaemia.

PMID- 25954649
TI  - To study the prevalence of impaired glucose tolerance in patients with hepatitis
      C virus related chronic liver disease.
AB  - BACKGROUND: Hepatitis C infection is a major cause of Chronic Liver Disease and
      the prevalence of Diabetes Mellitus is also high. Diabetes has been hypothesised
      as one of Extrahepatic manifestations of Hepatitis C. AIMS AND OBJECTIVES: The
      objective of our study was to study the prevalence of impaired glucose tolerance
      in patients with HCV related liver disease. STUDY DESIGN: The study was a
      prospective study conducted over a period of one and half year in Dayanand
      Medical College and Hospital, Ludhiana, Punjab, India. MATERIALS AND METHODS: The
      study was conducted taking total of 100 Hepatitis C virus positive patients above
      40 years of age who had fasting blood glucose levels >=110mg/dl on two occasions,
      24 hours apart. These patients underwent an oral glucose tolerance test. Blood
      sugar levels were tested at 0 and 2 hours. Based on the findings, patients were
      classified to have impaired glucose tolerance if levels were between 140-200mg/dl
      and frank diabetes if the levels were >= 200mg/dl. These findings were further
      assessed according to age, gender, Body Mass Index (BMI) Child Turcott Pugh score
      and Ultrasonography findings. STATISTICAL ANALYSIS: In our study all the
      statistical analysis was done using simple z-test and student t-test. The p
      values were calculated and the results assessed accordingly. RESULTS AND
      CONCLUSION: Out of 100 patients, 78 were males and rest females. The mean age of
      the study group was 55.89+/-11.22 years. Mean BMI of males was higher than in
      females (21.98kg/m2 v/s 20.13kg/m2). Maximum patients belonged to Child Turcott
      Pugh class C. Out of 100 patients,80 had cirrhosis on ultrasound. On doing
      Glucose Tolerance Test, 40 patients were found to have impaired glucose tolerance
      and one patient to be diabetic. The prevalence increased significantly as age
      increased and had significant relation with gender. On assessing according to
      BMI, there was not much significant relation but prevalence was significantly
      related to severity of disease.

PMID- 25954650
TI  - Primordial prevention: promoting preparedness for ebola virus disease.
AB  - BACKGROUND: India may face a danger of immediate spread of Ebola Virus Disease
      (EVD) if it enters the subcontinent. Preparedness for such a condition is a part
      of its prevention. Dentists form a sizeable chunk of healthcare in India and may
      help in augmenting the health care team at the time of such outbreaks. This paper
      details the development and evaluation of a specially tailored program for dental
      students and faculty for imparting knowledge on EVD and its prevention
      strategies. AIM: To assess the knowledge score for EVD and its prevention after
      attending a specially tailored program. MATERIALS AND METHODS: A
      multidisciplinary team was selected for content development and providing an
      insight on the topic. The program was attended by students and faculty members of
      Manav Rachna Dental College. The knowledge of the attendees about EVD was
      assessed at the end of the program through a structured questionnaire. The
      response rate was 96%. RESULT: According to the knowledge score attained, 52.4%
      of the participant had good knowledge level and 2.8% had poor knowledge level.
      There was no significant difference in knowledge scores between the participants
      having prior knowledge and those having no previous knowledge about the disease
      (p = 0.135). CONCLUSION: High response rate and good knowledge level attained by
      most of the participants established evidence of a successful program.

PMID- 25954651
TI  - Dynamics of electroencephalogram (EEG) in different stages of chronic kidney
      disease.
AB  - AIM: To study Electroencephalogram (EEG) in different stages of chronic kidney
      disease (CKD). MATERIALS AND METHODS: This observational study was carried out in
      the Department of Medicine, Jawaharlal Nehru Medical College, Sawangi (Meghe),
      Wardha conducted over a period of 24 months, spanning from August 2011 to August
      2013. Eighty three cases of CKD at different stages were studied. EEG was done in
      all the subjects and the various EEG dynamics like morphometric waveform
      patterns, symmetricity, amplitude were recorded and compared with the different
      stages of CKD. RESULTS: We found that characteristic changes were observed with
      increasing severity of CKD. Slow delta wave patterns were more prominent in stage
      5 (p<0.0001), asymmetric discharges, dysthymia, sharp wave transients and low
      amplitude wave forms were more prominent beyond Stage 4 (p<0.0001). CONCLUSION:
      EEG can be used as an effective tool for detection of subclinical or latent
      uremic encephalopathy. EEG findings which are characteristics of uremic
      encephalopathy can be present in CKD patients without overt signs of
      encephalopathy. So, EEG can be used as a prognostic indicator of response to
      clinical therapy of CKD.

PMID- 25954652
TI  - Comparison of Outcomes and Quality of Life between Hemodialysis and Peritoneal
      Dialysis Patients in Indian ESRD Population.
AB  - BACKGROUND: Hemodialysis (HD) and peritoneal dialysis (PD) are important renal
      replacement treatments in end stage renal disease (ESRD). There is paucity of
      data comparing outcomes and quality of life (QOL) between the two modalities in
      Indian scenario. MATERIALS AND METHODS: We followed 60 End stage renal disease
      patients (30 CAPD and 30 Maintenance hemodialysis) for a period of one year.
      Patients were analysed and compared for complications, physical quality of life
      and psychological well being with a two part self reported questionnaire at
      baseline and subsequently at six and twelve months. For the physical component
      appropriate sections of the McMaster Health Index Questionnaire (MHIQ) and for
      psychological component Psychological General Well-Being Index (PGWB) developed
      by Dupey was applied. RESULTS: The number of males and females in both groups
      were comparable (p-value > 0.05).The prevalence of diabetes mellitus, coronary
      artery disease, obesity and ischaemic heart disease was comparable in both groups
      (p-value>0.05). Significantly higher mortality was observed in patients
      undergoing HD (20% vs 0 %, p-value <0.05) at the end of study. At the end of
      study, 16.6% of patients undergoing HD were found to be anti HCV positive as
      compared to 3.33% in CAPD. Six episodes of CAPD peritonitis were observed (0.2
      episodes per catheter year). Significantly higher number of CAPD patients had
      negative responses between 2-4 at baseline and subsequently on follow ups in Part
      A of QOL questionnaire(86.7 vs 23.3 % at baseline, 80 vs 26.7% at 6 months, 80
      vs16.7 % at 12 months; p <0.05 ). Mean score in Part B of questionnaire was
      significantly higher in CAPD patients at baseline and at all follow ups (66.7+/
      11 vs 50.1+/-17 at baseline, 66.7+/-12.1 vs 53.32+/-16.3 at 6 months, 65.3+/-9.5
      vs 48.8+/-16.7 at 12 months , p <0.05) . CONCLUSION: CAPD patients have
      significantly better quality of life in physical as well as psychological aspects
      and have significantly lower mortality when compared with hemodialysis patients.

PMID- 25954653
TI  - Perrault syndrome - a rare case report.
AB  - Perrault syndrome is a rare disease comprising pure gonadal dysgenesis (46 XX)
      and sensorineural hearing loss in females and deafness alone in affected males.
      It is an autosomal recessive disorder. Over the years many additional features
      like marfanoid habitus and central nervous system findings have also been
      reported. Herein we report a case of sporadic Perrault syndrome in 18-year-old
      female who presented to our hospital with deaf mutism and primary amenorrhoea. On
      evaluation, the patient had hypergonadotropic hypogonadism, streak gonads and a
      normal karyotype (46 XX). Audiologic evaluation showed sensorineural deafness.
      The patient was started on hormone replacement therapy. She is on regular follow
      up. We present this case for its infrequent incidence and also to add to the ever
      expanding clinical spectrum of this disease. 

PMID- 25954654
TI  - Brain and Lung Abscesses in a 48-year-old Man with Focal and Segmental
      Glomerulosclerosis.
AB  - Focal segmental sclerosis (FSGS) is a common cause of idiopathic nephrotic
      syndrome in the adult population. A patient aged 48- year-old was admitted for
      evaluation of azotemia. Renal biopsy showed tip lesion FSGS and acute tubular
      necrosis. After methyl prednisolone pulse therapy, partial remission occurred,
      and he was stable with oral prednisolone and cyclosporine. Few months later two
      serious complications including lung and brain abscess occurred. We describe a
      case of FSGS with lung and brain abscess, who responded to medical management. 

PMID- 25954655
TI  - A Rare Case of Mixed Connective Tissue Disease (MCTD) with Intricate Features of
      Lupus, Polymyositis and Rheumatoid Arthritis Presenting with Severe Myositis.
AB  - Mixed connective tissue disease (MCTD) includes clinical and laboratorial
      manifestations of systemic lupus erythematosus, scleroderma and polymyositis
      along with high titres of anti-U1RNP antibodies. In the initial phases of the
      disease, muscle enzyme levels increase but the disease remains generally
      subclinical. Presentation with myositis is uncommon. Our objective is to report a
      rare case of a patient who presented with a severe onset of myositis
      characterized by dysphagia, an increase in myopathy and joint involvement
      suggestive of RA. The patient was initiated on pulse corticosteroid therapy along
      with methotrexate in view of her elevated Creatine Kinase levels and biopsy
      findings that were suggestive of severe myositis. The patient showed clinical and
      laboratory improvement with this regimen. Though severe myositis and arthritis
      can occur in overlap syndrome, MCTD evolved as a separate disease entity due to
      presence of high titres of Anti U1-RNP antibodies. The authors emphasize that
      this is an extremely rare presentation of MCTD with only two previous cases seen
      in literature, one of a 13 year old child and the other being an adult female
      both of whom had evidence of myositis on presentation. 

PMID- 25954656
TI  - Cronkhite-Canada Syndrome (CCS)-A Rare Case Report.
AB  - Cronkhite-Canada syndrome (CCS) is an extremely rare non-inherited condition
      characterized by gastrointestinal hamartomatous polyposis, alopecia,
      onychodystrophy, hyperpigmentation, weight loss and diarrhoea. The aetiology is
      probably autoimmune and diagnosis is based on history, physical examination,
      endoscopic findings of gastrointestinal polyposis, and histology. The disease is
      very rare; approximately 450 cases of CCS have been reported worldwide. The
      author reports a case of CCS in an elderly Indian male. 

PMID- 25954657
TI  - Longitudinal Telomere Erosion in Lymphocyte Subsets of Patients with
      Atherosclerotic Peripheral Arterial Disease (PAD).
AB  - Telomere attrition has been linked to accelerate vascular ageing and seems to
      predispose for vascular disease. Our aim was to study the telomere length
      dynamics over time and in subsets of leukocytes from 15 patients with peripheral
      arterial disease (PAD). The mean telomere length in subsets of leukocytes of
      patients with PAD was in the normal range of age-related telomere length values
      from healthy individuals. However, we found significant higher telomere attrition
      for T-cells from patients with PAD over a time period of six months when compared
      to the controls. The higher telomere loss in T-cells of patients with PAD most
      likely reflects a higher cell turnover of this leukocyte subset, which is
      involved in the process of chronic inflammatory disease underlying vascular
      disease. Further studies are needed to confirm these data and to assess how far
      this T-cell telomere attrition will correlate to the extent of the disease. 

PMID- 25954658
TI  - Evaluation of quantum of disability as sequelae of electric burn injuries.
AB  - BACKGROUND: All will agree that invention of electricity has changed the world.
      Today nobody can think of living without an uninterrupted supply. Electricity is
      definitely a boon to the mankind but this turns into a curse when it becomes a
      cause of disaster. Electrical burn injuries are the most destructive injuries
      with a potential of causing significant functional disability and extensive
      disfigurement in the survivors. MATERIALS AND METHODS: We carried out a
      retrospective observational study on the 110 patients of electric burns admitted
      to our hospital between January 2007 and October 2014. The aim of the study was
      to determine the demographic and clinical profile of patients who had sustained
      electrical burn injury, with a special emphasis on limb loss. Section-2 of
      Workman's Compensation Act 1923 was used for the calculation of an individual's
      disability due to amputation. All the data was analysed using method of simple
      percentages and presented in a tabular form. RESULT: Forty eight patients
      (43.63%) of electric burn belonged to the age group of 21-30 y, with male
      preponderance (M:F:: 93.6 : 6.4). This shows that the individual affected more
      often are invariably the breadwinners of the family.Twenty four, out of these 110
      patients have undergone one or more than one amputation. Significantly the
      numbers of upper limb amputations have exceeded any other amputation in this
      study. Mortality in patients of electrical burns is 6.36% in comparison to
      mortality of 45.67% in all burn patients. CONCLUSION: Loss of upper limb
      completely reduces the earning capacity of an individual. Future and fortune of
      the individual's family is jeopardized. Such accidents can be prevented by
      following safety norms and simple precautions while using the electrical
      equipment.

PMID- 25954659
TI  - Keystone flap: versatile flap for reconstruction of limb defects.
AB  - BACKGROUND: There is always a constant search for a new solution to tackle
      defects in the limbs. The technique has to be simple, easily reproducible and
      performed within a short duration. The answer is keystone island flap keystone
      flap is a simple, less time consuming, durable and easily reproducible option to
      reconstruct most of the limb defects. AIM: The aim of this article is to study
      the usefulness of keystone flap in reconstruction of various upper and lower limb
      defects. MATERIALS AND METHODS: This retrospective review involves study of 20
      patients undergoing keystone flap reconstruction for various defects from 2012 to
      2014. Patient demographic data, medical histories, comorbidities, surgical
      indications, defect characteristics and locations, hospitalization, complications
      and follow-up were evaluated and are presented as uncontrolled case series.
      RESULTS: Ages of the patients were ranging from 18 to 65 y with an average of
      38.75y. Among the defects, 10 were following trauma (50%), 5 were due to tumour
      resection (25%), 3 followed debridement of abscess (15%) and another 2 defects
      were due to surgical wound dehiscence (10%). The largest defect covered by this
      flap in our study measured 45 x 18 cm and the smallest defect was 8 x4 cm. The
      average intra-operative time was 45.5 min (range 20-90 min). Fourteen flaps were
      done to cover lower limb defects (70%), 4 for upper limb defects and 2 were for
      defects in the axilla. Partial flap necrosis was observed in one case. The
      average duration of hospital stay of patients was 3.45 d. All patients were
      followed until they achieved stable, healed wound.The overall success rate was
      95%. CONCLUSION: Keystone flap can be safely used to cover various limb defects
      with minimal pain, a sensate cover and excellent cosmetic outcome, minimizing the
      need for microsurgical techniques or prolonged operative time.

PMID- 25954660
TI  - Safe, Effective and Easily Reproducible Fusion Technique for CV Junction
      Instability.
AB  - INTRODUCTION: The Craniovertebral junction (CVJ) refers to a bony enclosure where
      the occipital bone surrounds the foramen magnum, the atlas and the axis
      vertebrae. Because of the complexity of structures, CVJ instability is associated
      with diagnostic and therapeutic problems. Posterior CV fusion procedures have
      evolved a lot over the last couple of decades. There has been a lookout for one
      such surgical procedure which is inherently safe, simple, easily reproducible and
      biomechanically sound. In our study, we present the initial experience the cases
      of CV junction instrumentation using O-C1-C2 screw & rod construct operated by
      the author. AIMS AND OBJECTIVES: The current study is a descriptive analysis of
      the cases of CVJ instability treated by us with instrumentation using O-C1-C2
      screw and rod construct fusion technique. MATERIALS AND METHODS: It is a
      retrospective, analytical study in which cases of CV junction instability
      operated by the author between January 2010 to March 2014 were analysed using
      various clinical, radiological and outcome parameters. CONCLUSION: CV junction
      instrumentation using O-C1-C2 screw and rod construct fusion technique proved to
      be safe, effective, easily reproducible and biomechanically sound technique which
      can be adopted by all surgeons who may be at any stage of their learning curve.

PMID- 25954661
TI  - Gallbladder cancer presenting with brain and bone metastasis: case report.
AB  - Although gallbladder cancer is a rare disease worldwide, north India has one of
      the highest incidences of this disease. We report a case of asymptomatic gall
      bladder cancer with brain metastasis. The patient presented with a scalp lump as
      the sole presenting feature, with no symptoms attributable to abdominal
      malignancy. Previously, the lump had been incised by a local practitioner who had
      probably misdiagnosed it as an abscess. 

PMID- 25954662
TI  - Small intestinal obstruction secondary to jejunal trichobezoar removed per anum
      without an enterotomy: a case report.
AB  - Trichobezoars can rarely present with obstruction. This is usually due to
      collection of a hair ball in the stomach. We encountered an interesting case of
      small bowel obstruction due to a jejunal trichobezoar. The treatment generally is
      an enterotomy with removal of the hair ball. We report a case of a 29-year-old
      post partum female who presented to us with sub acute intestinal obstruction.
      Exploratory laparotomy revealed an impacted mass in the distal jejunum which was
      removed per anum without an enterotomy. Postoperative gastroscopy did not show
      trichobezoar in the stomach. This case highlights the importance of trichobezoar
      as a differential diagnosis in young women with small bowel obstruction that can
      be treated without an enterotomy and avoiding the risks and morbidities
      associated with it. 

PMID- 25954663
TI  - Familial Adenomatous Polyposis (FAP)-A Case Study and Review of Literature.
AB  - Familial adenomatous polyposis (FAP) is a syndrome characteristically having
      numerous (hundreds to thousands) polyps in the epithelium of the large intestines
      with an autosomal dominant inheritance caused by germ line mutations in
      adenomatous polyposis coli (APC) gene in chromosome 5q21. Most FAP patients have
      a family history of colorectal polyps and cancer but 25-30% of them are "de
      novo", without any clinical or genetic evidence of FAP in family members.
      Prophylactic proctocolectomy is required in almost all patients since all
      affected patients inevitably develop cancer. We report a case of a 32-year-old
      man who presented with vague abdominal complaints without any family history,
      which on evaluation as found to have multiple colorectal polyps and underwent a
      prophylactic proctocolectomy with end continent ileostomy. Two of his children
      were evaluated and found to have multiple colorectal polyps on colonoscopy and
      have been advised regular follow up annually. In conclusion, patients with FAP
      may present with vague abdominal complaints and without any family history, hence
      need to be carefully evaluated. Good patient compliance is of prime importance in
      deciding the treatment and surveillance modality subsequently determining the
      prognosis of patients with FAP. 

PMID- 25954664
TI  - Isolated renal hydatid cyst masquerading as cystic renal cell carcinoma: a case
      report.
AB  - Incidentally detected renal cysts are always a diagnostic challenge especially
      when they present with equivocal features on imaging. Proper diagnosis is of
      paramount importance as it affects the treatment decisions. Septal and nodular
      enhancement on computed tomography (CT) is the strongest predictor of malignant
      process. A multilocular cystic lesion with heterogeneity on CT goes in favour of
      hydatid disease. Though the treatment in both these cases is surgical excision, a
      more careful study of image may ease the treatment planning process much more. We
      report a case in middle aged lady who presented with vague abdominal pain with
      loss of weight, who was found to have a cystic mass in the upper pole of the left
      kidney on imaging turned out to be hydatid cyst though the radiological features
      were in favour of cystic renal cell carcinonoma. 

PMID- 25954665
TI  - Bilobed lipoma of submandibular region: an unusual presentation.

PMID- 25954666
TI  - Tuberculosis biliary stricture simulating as cholangiocarcinoma.

PMID- 25954667
TI  - To evaluate the effect of perceived stress on menstrual function.
AB  - INTRODUCTION: Menstrual irregularities affect 2-5% of childbearing women, a
      number that is considerably higher among females under constant stress during a
      cycle. AIM: To study the effect of perceived stress on cycle length, regularity
      and dysmenorrhoea. MATERIALS AND METHODS: A cross-sectional study was conducted
      on 100 female undergraduate students of a medical college. A questionnaire along
      with the Perceived Stress Scale (PSS) and Pictorial Blood Assessment Chart (PBAC)
      was provided to the students. The menstrual pattern was then correlated with the
      PSS using the chi- square test and the Fisher's Exact test for statistical
      analysis. OBSERVATIONS AND RESULTS: Out of the 100 undergraduate medical
      students, 30 students had a PSS score >20 while 70 had a score <=20. An
      association was established between high stress levels (PSS >20) and menstrual
      irregularity. No association was found in students with PSS >20 with
      hypomenorrhoea, menorrhagia, dysmenorrhoea, long cycle length and short cycle
      length. CONCLUSION: High stress levels (PSS >20) was associated with only
      menstrual irregularities and not with duration, amount of flow or dysmenorrhoea.
      Hence, other causes should be looked for in young women complaining of menstrual
      problems before stress is assumed to be the cause.

PMID- 25954668
TI  - Utility of microbiological profile of symptomatic vaginal discharge in rural
      women of reproductive age group.
AB  - INTRODUCTION: Symptomatic vaginal discharge is the most frequent symptom in women
      of reproductive age group. Owing to social stigma majority of affected women
      hesitate to seek medical consultation. Therefore the actual incidence of vaginal
      discharge is much more than what is reported. The aim of the study is to
      determine the microbiological profile of symptomatic vaginal discharge in rural
      area and its utility in the management of genital tract infection. MATERIALS AND
      METHODS: This was a descriptive type of observational study, conducted in
      sexually active women of reproductive age group (18-45 years) attending the
      OPD/IPD of Obstetrics and Gynaecology Department of National Institute of Medical
      Sciences, Shobhanagar, Jaipur (Rajasthan), over a period of 18 months from June
      2012 to December 2013. Hundred sexually active non pregnant women of reproductive
      age group (18-45 years) were included in the study. After taking consent general
      physical examination along with pelvic examination was performed. Two high
      vaginal swabs and blood sample were collected for various tests. Hanging drop
      preparation was immediately made. This was followed by gram staining and culture.
      Chlamydia trachomatis IgM antibody was detected by ELISA method. RESULTS: Out of
      100 women with symptomatic vaginal discharge, specific diagnosis was obtained in
      89% of cases whereas no specific aetiology was found in 11% cases. Mean age was
      32.60 years. Fifty-three percent patient had Bacterial vaginosis, candidiasis was
      found in 14% cases, 16% had Chlamydia trachomatis infection while Trichomonas
      vaginalis infection was detected in 6% cases. Homogenous discharge was most
      prevalent (52%), followed by mucopurulant discharge in 23% of women. CONCLUSION:
      Patient with symptomatic vaginal discharge need to be actively managed with
      appropriate antimicrobial agents. Judicious management may be helpful in
      prevention of HIV, HPV, CIN and post infection sequelae.

PMID- 25954669
TI  - Gossypiboma mimicking as dermoid cyst of ovary: a case report.
AB  - Gossypiboma is a rare condition caused by retained postoperative foreign bodies.
      The condition is under reported because of diagnostic difficulties and
      medicolegal implications associated with it. It may mimic a benign or malignant
      soft-tissue tumour in the abdomen and pelvis. A 22-year-old woman presented with
      non specific symptoms and was referred to us with radiological diagnosis of
      dermoid cyst. On laparotomy the mass was proved to be a gossypiboma resulted from
      gauze which was retained in caesarean section done two years back. Although
      gossypiboma is rarely seen in daily clinical practice, it should be considered in
      the differential diagnosis of postoperative patients presenting with non specific
      complains and lump abdomen. Despite thorough history, physical examination,
      laboratory, and radiographical findings, usually gossypibomas are not suspected
      and remain an accidental finding. Employment of all preventive measures during
      surgical procedures and high index of suspicion in post operative patients are
      the key stones in its management. 

PMID- 25954670
TI  - A rare case of heterotopic pregnancy with ruptured left rudimentary horn
      pregnancy.
AB  - Heterotopic pregnancy(HP) occurs when intrauterine and ectopic pregnancies
      coexist. We report a case of HP at 14 wk of gestation presenting as ruptured left
      rudimentary horn ectopic pregnancy with live intrauterine gestation and was
      managed with emergency laparotomy followed by resection of left rudimentary non
      communicating horn of uterus. The intrauterine pregnancy continued uneventfully.
      A female baby was delivered vaginally at 41 wk following induction of labour. 

PMID- 25954671
TI  - Occupational radiation exposure from C arm fluoroscopy during common orthopaedic
      surgical procedures and its prevention.
AB  - BACKGROUND: Image intensifiers have become popular due to the concept of
      minimally invasive surgeries leading to decreasing invasiveness, decreased
      operative time, and less morbidity. The drawback, however, is an increased risk
      of radiation exposure to surgeon, patient and theatre staff. These exposures have
      been of concern due to their potential ability to produce biological effects. The
      present study was embarked upon to analyse the amount of radiation received by
      orthopedic surgeons in India using standard precautionary measures and also to
      bring awareness about the use of image intensifier safety in everyday practice.
      MATERIALS AND METHODS: Twelve right-handed male orthopedic surgeons (4 senior
      consultants, 5 junior consultants and 3 residents) were included in a three month
      prospective study for radiation exposure measurement with adequate protection
      measures in all procedures requiring C Arm fluoroscopy. Each surgeon was provided
      with 5 Thermo Luminescent Dosimeter (TLD) badges which were tagged at the level
      of neck, chest, gonads and both wrists. Operative time and exposure time of each
      procedure was recorded. Exposure dose of each badge at the end of the study was
      obtained and the results were analysed. RESULTS: Mean radiation exposure to all
      the parts were well within permissible limits. There was a significantly positive
      correlation between the exposure time and the exposure dose for the left wrist
      (r=0.735, p<0.01) and right wrist (r=0.58, p<0.05). The dominant hand had the
      maximum exposure overall. CONCLUSION: Orthopaedic surgeons are not classified
      radiation workers. The mean exposure doses to all parts of the body were well
      within permissible limits. Nothing conclusive, however, can be said about the
      stochastic effects (chance effects like cancers). Any amount of radiation taken
      is bound to pose an additional occupational hazard. It is thus desirable that
      radiation safety precautions should be taken and exposures regularly monitored
      with at least one dosimeter for monitoring the whole-body dose.

PMID- 25954672
TI  - Unusual Presentation of a Primary Ewing's Sarcoma of the Spine with Paraplegia: A
      Case Report.
AB  - Ewing's sarcoma is a primary malignancy of the bone affecting individuals in the
      second decade of life. Primary sarcomas of the spine are rare and the occurrence
      of Primary Ewing's sarcoma in the spine is very rare. Ewing's sarcoma occurring
      in the spine is divided into two types, Ewing's sarcoma of sacral spine which are
      very aggressive with poor prognosis and Ewing's sarcoma of the non sacral spine
      which is an extremely rare occurrence. Patient may present with neurological
      deficit when the tumour extends into the spinal canal causing spinal cord
      compression. Magnetic resonance imaging (MRI) is very sensitive in diagnosing the
      tumour and defining the extent of the tumour. Here we report an 18-year-old boy
      who presented with back pain and complete paraplegia of two months duration. The
      MRI gave a differential diagnosis of infective pathology due to the fluid
      collection in the paraspinal region, followed by primary malignancy as the second
      diagnosis. Patient underwent posterior spinal decompression and stabilization,
      and intaoperatively there was significant collection of pus whose culture showed
      no growth. The histopathology and immunohistochemistry studies confirmed the
      diagnosis of Ewing's sarcoma and patient was started on combination chemotherapy
      and radiotherapy. 

PMID- 25954673
TI  - Honey versus diphenhydramine for post-tonsillectomy pain relief in pediatric
      cases: a randomized clinical trial.
AB  - INTRODUCTION: Tonsillectomy is one of the most common surgeries done worldwide
      and often the first one a child sustains. Pain relief after tonsillectomy is
      helpful for oral feeding after surgery. Acetaminophen and diphenhydramine have
      been conventionally used for reducing pain. This study was conducted to compare
      the effect of honey and diphehydramine on pain relief after tonsillectomy.
      MATERIALS AND METHODS: For this randomized clinical trial study, 120 patients of
      5 to 12 years undergoing tonsillectomy were recruited. The patients were divided
      into four groups randomly. After tonsillectomy and beginning of eating, Group A
      took 5cc honey alone every hour, Group B was given 5 cc 50% honey (mixed with
      water) every hour, group C was treated with 1mg/kg diphenhydramine every 6 hours
      and group D was observed without any intervention. In all patients, severity of
      the pain was evaluated by ocher questionnaire at recovery, and 3, 6, 12 and 24
      hours after surgery. The data were analyzed using ANOVA and the repeated measures
      ANOVA (SPSS version 17). RESULTS: The repeated ANOVA showed a significant
      decreasing trend of pain scores during the study for both pain scales (p <0.05),
      but the rate of trend was similar between the four groups (p > 0.05). No
      statistically significant difference in pain was detected among the groups.
      CONCLUSION: Although honey can help the pain decrease, more research is supported
      for confirmation of this effect.

PMID- 25954674
TI  - Effect of vitamin d3 supplement in glycemic control of pediatrics with type 1
      diabetes mellitus and vitamin d deficiency.
AB  - BACKGROUND: Glycemic control prevents microvascular complications in patients
      with type I diabetes mellitus such as retinopathy, nephropathy and neuropathy
      that influences quality of life. Some studies show the immunomodulatory effect of
      vitamin D in synthesis and secretion of insulin. AIMS: In this study we evaluate
      glycemic changes after vitamin D3 supplement in children with type I diabetes
      mellitus and vitamin D deficiency. MATERIALS AND METHODS: In children with type I
      diabetes mellitus, level of vitamin D and HbA1C was measured. Patients with type
      I diabetes mellitus who had vitamin D deficiency (25OHD < 50 nmol/lit) treated
      with 300,000 units of vitamin D3. Calcium supplement (40mg/kg/day) divided in two
      doses in order to avoid hungry bone was also used. After three months, 25OHD and
      HbA1C were measured again. Differences, in mean +/- SD HbA1C and 25OHD were
      evaluated before and after the study. RESULTS: Mean +/- SD HbA1C was 9.73+/-1.85
      before the study which was diminished to 8.55+/-1.91 after vitamin D3 supplement
      treatment. This decline has a significant difference (p-value < 0.0001). Mean +/-
      SD 25OHD was 17.33+/-8.97 nmol/lit before the study which is increased to 39.31+/
      14.38 nmol/lit after treatment with vitamin D3 supplement. This increase also has
      a significant difference (p-value < 0.0001). Vitamin D3 supplement causes the
      improvement of HbA1C in all groups of glycemic control including HbA1C <7.8, 7.8
      9.9, and >9.9. This supplement transfer patients toward better glycemic control
      for the entire group (p-value < 0.0001). CONCLUSION: Vitamin D3 supplement
      improves HbA1C in pediatrics with type I diabetes mellitus and vitamin D
      deficiency.

PMID- 25954675
TI  - Thrombocytopenia with Unilateral Dysplastic Radius- Is it Thrombocytopenia -
      Absent Radius (TAR) Syndrome?
AB  - Thrombocytopenia - absent radii (TAR) syndrome is an autosomal recessive genetic
      rare disorder with hypomegakaryocytic thrombocytopenia and bilateral absent
      radius that may have additional anomalies. This disorder is characterized by
      thrombocytopenia resulting in potentially severe bleeding episodes primarily
      during infancy. We report the case of a 7-day-old term appropriate for
      gestational age (AGA) male baby, product of non consanguineous marriage presented
      with bloody loose stool, right sided upper limb deformity and paleness of the
      body, was diagnosed as TAR syndrome with some atypical presentation. Such type of
      atypical presentation has not been previously reported in a case with TAR
      Syndrome.Patient was managed in our hospital with packed cell transfusion and two
      units platelets concentrates transfusion, Intra-venous antimicrobials, and other
      supportive treatment. He gradually improved and was discharged after seven days
      of hospital stay with advice to consult orthopedic surgeon for opinion regarding
      limb reconstruction. 

PMID- 25954676
TI  - Pulmonary Hemorrhage (PH) in Extremely Low Birth Weight (ELBW) Infants:
      Successful Treatment with Surfactant.
AB  - We report a case of an extremely low birth weight (ELBW) infant presenting with
      pulmonary hemorrhage (PH) in which we have given surfactant after an acute
      episode of bleeding with severe intractable hypoxemia. Surfactant replacement
      therapy showed improvement in Mean Airway Pressure (MAP) and oxygenation indices.
      Our case suggests that surfactant replacement therapy is useful in PH. 

PMID- 25954677
TI  - Nephropathic Cystinosis Presenting as Renal Fanconi Syndrome without Glycosuria.
AB  - Renal Fanconi syndrome is diagnosed by its cardinal features of glycosuria
      without diabetes, aminoaciduria, phosphaturia, and renal tubular acidosis. It is
      often associated with hypokalaemia, hypophosphatemia and rickets. We report a
      seven-year-old boy with nephropathic cystinosis who presented with all the
      cardinal features of renal Fanconi syndrome associated with rickets, pathological
      fractures, stage IV chronic kidney disease (CKD) and hypothyroidism. Slit-lamp
      examination of the cornea confirmed the diagnosis. However glycosuria was
      conspicuously absent. Whenever there are features of rickets with failure to
      thrive and recurrent vomiting renal rickets should be ruled out. Cystinosis is
      one such disorder and we report this case due its rarity and interesting clinical
      presentation. 

PMID- 25954678
TI  - Prevalence of Beta-Cell, Thyroid and Celiac Autoimmunity in North Indian Children
      with Recent Onset Type 1 Diabetes (T1D).
AB  - There is wide variation in the prevalence of pancreatic and other major
      autoantibodies in different patient populations of Type 1 diabetes (T1D) across
      continents and even within countries. The data on frequency of associated
      autoimmunity Indian children with T1D is limited. A retrospective record review
      of 310 children aged 7.28+/-3.3 y (range 0.7-15 y) with recently diagnosed T1D
      attending our Pediatric Diabetes Clinic between April 2004 to September 2014,
      showed positivity for anti-GAD65, anti-IA2b, anti-TPO and anti-tTGA of 50%
      (64/128), 16% (12/72), 18.7% (23/123) and 22% (47/212) respectively. The
      male:female ratio in patients with anti-GAD, anti-TPO and anti-tTG positivity was
      1.3, 0.7 and 0.6 respectively. In conclusion, our patient cohort exhibited a
      moderate prevalence of anti-GAD 65, low prevalence of anti-TPO and high
      prevalence of anti-tTGA autoantibodies as compared to previous reports. Male
      preponderance was noted in children with GAD65 positivity. 

PMID- 25954679
TI  - Giant serpentine vertebrobasilar aneurysm with vertebral artery hypoplasia and
      fenestration- a case report.
AB  - Intracranial aneurysm in paediatric age group is rare and association of the
      aneurysm with congenital vertebral artery anomaly is further rarer. We describe
      such a case in an 11-year-old male patient who consulted a paediatrician about
      headache and vertigo, and a noncontrast CT (NCCT) head revealed peripherally
      calcified hyperdense mass in prepontine and basal cisterns. Magnetic resonance
      imaging (MRI) including contrast enhanced magnetic resonance angiography (MRA)
      revealed partially thrombosed giant serpentine aneurysm of right vertebrobasilar
      artery and contralateral hypoplastic vertebral artery with fenestration. The
      nondominant left vertebral artery gave off the posterior inferior cerebellar
      artery, then became hypoplastic and joined with its counterpart to form the
      basilar artery. This pattern is called as type 9. The patient was kept on
      conservative management. The role of MRI in this congenital anomaly and its
      association with vertigo and aneurysm of vertebro-basilar artery is discussed. 

PMID- 25954681
TI  - A rare case of isolated partial anomalous pulmonary venous connection to the
      inferior vena cava.

PMID- 25954680
TI  - Tetra-phocomelia: a rarest of rare case.
AB  - We present a rarest of rare case of Tetra-Phocomelia evaluated by antenatal
      Ultrasonography. It is a condition seen in 0.62 per 100,000 live births. An
      ultrasonogram was done at 18 wk of pregnancy to assess the fetus and after
      termination gross specimen was evaluated and X-ray infantograms were done to
      confirm the findings. The case showed classic Tetra-Phocomelia with limbs like
      flippers of a seal. Our findings make it rarest of rare as only few cases have
      been so far reported. 

PMID- 25954682
TI  - Multimodality imaging of hemangiomas-pictorial essay.
AB  - Both hemangiomas and vascular malformations are endothelial malformations that
      closely resemble normal vessels and can be found in all organs of the human body.
      This pictorial essay encompasses a spectrum of imaging appearances of hemangiomas
      and vascular malformations. Familiarity of the MR and CT findings can help
      differentiate these lesions, to confirm the suspected diagnosis, classify the
      anomaly and document the associated abnormalities. 

PMID- 25954683
TI  - Comparative evaluation of dexmedetomidine and esmolol on hemodynamic responses
      during laparoscopic cholecystectomy.
AB  - BACKGROUND: The advent of laparoscopic surgery has benefited the patient and
      surgeon; however creation of pneumoperitoneum for same has bearings during the
      perioperative period. These effects of pneumoperitoneum are associated with
      significant haemodynamic changes, increasing the morbidity of the patient. AIM:
      The present study compared the efficacy of dexmedetomidine and esmolol on
      hemodynamic responses during laparoscopic cholecystectomy Materials and Methods:
      A total of 90 patients aged 20-60 y, American Society of Anaesthesiologists (ASA)
      physical status I or II, of either sex, planned for laparoscopic cholecystectomy
      were included. The patients were randomly divided into three groups of 30 each.
      Group D received dexmedetomidine loading dose 1 mcg/kg over a period of 15 min
      and maintenance 0.5 mcg/kg/h throughout the pneumoperitoneum. Group E received
      esmolol loading dose 1 mg/kg over a period of 5 min and maintenance 0.5 mg/kg/h
      throughout the pneumoperitoneum. Group C received same volume of normal saline.
      MEASUREMENTS: Heart rate (HR), systolic blood pressure, diastolic blood pressure
      and mean arterial pressure (MAP) were recorded preoperative, after study drug,
      after induction, after intubation, after pneumoperitoneum at 15 min intervals,
      post pneumoperitoneum and postoperative period after 15 min. Propofol induction
      dose, intraoperative fentanyl requirement and sedation score were also recorded.
      RESULTS: In group D, there was no statistically significant increase in HR and
      blood pressure after pneumoperitoneum at any time intervals, whereas in Group E,
      there was a statistical significant increase in MAP after pneumoperitoneum at 15,
      45, and 60 min only and HR during the whole pneumoperitoneum period. There was a
      significant decrease in induction dose of propofol and intraoperative fentanyl
      requirement in Group D and E, compared to Group C (p<0.0001). CONCLUSION:
      Dexmedetomidine is more effective than esmolol for attenuating the hemodynamic
      response to pneumoperitoneum in elective laparoscopic cholecystectomy.
      Dexmedetomidine and esmolol also reduced requirements of anaesthetic agents.

PMID- 25954684
TI  - Intraventricular haemorrhage as a complication of sub mucosal infiltration of
      adrenaline.
AB  - Adrenaline infiltration is a widely used technique in head-neck and ENT surgeries
      to provide bloodless surgical field. However, use of adrenaline has been
      associated with hemodynamic changes which can be life threatening at times.
      Therefore, use of higher concentrations of adrenaline should be avoided and a
      close hemodynamic monitoring is required with use of other vasopressors. In the
      present case report, a young male died because of intraventricular bleeding
      caused by adrenaline infiltration during rhinoplasty. 

PMID- 25954685
TI  - Burden of care on caregivers of schizophrenia patients: a correlation to
      personality and coping.
AB  - BACKGROUND: Schizophrenia is a mental disorder where the caregivers are likely to
      face increasing levels of burden and stress. The present study aims to explore
      the relation between burden of care on the caregivers of schizophrenic patients
      with various psychological parameters including their coping strategies,
      personality type, overall quality of life and socio-demographic details.
      MATERIALS AND METHODS: The participants included in the study (n=110) were
      administered a socio-demographic data sheet and questionnaires to assess their
      personality type, burden, quality of life, and coping mechanisms of having a
      schizophrenic in the family. These questionnaires were administered in individual
      setting. Their informed consent was taken prior to the administration of tools
      and their privacy was taken care of. The data obtained was analysed
      statistically. RESULTS: Most of the caregivers were females. The caregivers were
      observed to have moderate and high levels of burden. Burden on the caregivers
      showed a significant correlation with psychoticism and their overall quality of
      life. A significant correlation was seen between the levels of coping and
      extrovert type of personality, and also with the environmental health of the
      caregivers. Caregivers belonging to nuclear families coped better than those of
      joint families. CONCLUSION: The study concludes that certain personality traits
      like psychoticism and certain social traits such as living in joint families can
      increase the risk of caregiver burden in looking after family members suffering
      from schizophrenia. A need for psychological assistance for the vulnerable
      caregivers to help them reduce the burden levels and employ positive coping
      strategies has, therefore, been emphasized in our study.

PMID- 25954686
TI  - Palmoplantar psoriasis- ahead in the race-a prospective study from a tertiary
      health care centre in South India.
AB  - BACKGROUND: Psoriasis is a common and chronic T cell mediated skin disorder with
      varied clinico-morphological types. Most of the published studies have reported
      chronic plaque type psoriasis to be the commonest type. AIM: To find the
      incidence of palmoplantar psoriasis in a tertiary health care centre in South
      India. MATERIALS AND METHODS: A prospective study done over a period of six
      months recruiting the patients attending the Dermatology out-patient department
      in a tertiary health care centre. RESULTS: Incidence of palmoplantar psoriasis
      was found to be highest among all morphological forms of psoriasis. CONCLUSION:
      Incidence of palmoplantar psoriasis is under-expressed. It is actually ahead in
      the race.

PMID- 25954687
TI  - A study on the prescribing pattern of drugs for acne in a tertiary care teaching
      hospital in odisha.
AB  - BACKGROUND: Acne vulgaris is a common disease of the skin affecting the socially
      vulnerable young age group. There are multitudes of treatment options available
      but till now no studies have been reported to demonstrate the current prescribing
      pattern of drugs in acne vulgaris. AIM: To study the prescribing pattern of drugs
      in acne in a tertiary care teaching hospital in Odisha, India. MATERIALS AND
      METHODS: The study was an observational study conducted for a period of one year
      on patients more than 10 yeras age and having acne attending the Skin & VD OPD.
      Drug induced acne and acneiform eruptions were excluded. RESULTS: A total of 1210
      prescriptions of acne were analysed. The male to female ratio was 1:1.29. Most
      patients presented with grade 2 (60%) acne followed by grade 3 (20.99%). Out of
      prescribed drugs, 47.44% were oral and 52.56% were topical formulations. Oral
      isotretinoin (68.10%) was the most frequently prescribed drug among oral
      formulations. Doxycycline (54.18%) was the most preferable oral antibiotic. The
      average number of drugs per prescription was 3.003. Polypharmacy was preferred
      over monotherapy. CONCLUSION: In the management of acne, judicious and early
      intervention with oral isotretinoin improves the overall treatment outcome, the
      fact which has increased its use in acne patients.

PMID- 25954688
TI  - Evaluation of suspected cosmetic induced facial dermatoses with the use of Indian
      standard series and cosmetic series patch test.
AB  - INTRODUCTION: Awareness about skin beauty or cosmetic elegance has received
      worldwide attention in the present day youth oriented society. Along with careful
      detailed history and thorough examination patch test is considered cornerstone in
      diagnosis of allergic contact dermatitis. MATERIALS AND METHODS: Fifty patients
      suspected clinical diagnosis of contact facial dermatitis due to attended the
      Department of Dermatology, were included in a hospital based study. The patch
      test was applied on the upper back of using 32 allergens present in Indian
      cosmetic series and 20 known allergens in Indian standard battery series procured
      from Systopic Pharmaceutical Ltd, after applying the patch test, the patient was
      asked to come after 48h and 72h for reading the results of the patch test.
      RESULTS: Out of 50 patients there were 32 (64%) females (housewives 36%) patients
      and 18 (36%) male (farmers 12%). Itching was the most common presenting symptom
      in 39 patients (78%) least was hypopigmentation and pain in 2%. Forehead was the
      most common site of involvement in 25 patients (50%) least were cheeks in 15
      patients (30%). Erythema was the commonest morphological presentation seen in 36
      patients (72%). Hair dye was suspected in maximum number of patients that is 13
      (26%). Most common antigen showing patch test positivity was paraphenylenediamine
      in nine patients (18%). There are significantly more chances of developing
      positive test reaction with Indian standard series compared to cosmetic series.
      (p=.0053 using Fischer Exact test). CONCLUSION: In India there is no legislation
      regarding labeling ingredients on cosmetics as in the western countries, so
      labelling of the contents of cosmetic products should be the main challenge in
      cosmetic dermatitis is to identify.

PMID- 25954689
TI  - Congenital hyponychia of the hands with lymphangiectases: a new entity?
AB  - We present a case of 58-year-old woman with congenital hyponychia of the ten
      fingers and oedema of the fingertips as the only cutaneous alterations. There was
      no associated systemic condition or additional ectodermal abnormality. The biopsy
      showed lymphangiectases mainly confined to the papillary dermis but also in the
      reticular dermis. We propose the designation "congenital hyponychia of the hands
      with lymphangiectases" for this apparently not previously described condition. 

PMID- 25954690
TI  - Feasibility and response of concurrent weekly docetaxel with radical radiotherapy
      in locally advanced head and neck squamous cell carcinoma.
AB  - OBJECTIVE: (1) To study the feasibility, adverse effects and response of
      concurrent weekly Docetaxel with radical radiotherapy in inoperable locally
      advanced head and neck squamous cell carcinoma. (2) To assess the compliance and
      tolerance of weekly Docetaxel with radiotherapy. MATERIAL AND METHODS: Twenty one
      patients with stage III and IV head and neck squamous cell carcinoma satisfying
      inclusion criteria were selected and treated with conventional external
      radiotherapy of 70Gy in 35 fractions with weekly concurrent Docetaxel (15mg/sqm),
      administered one hour before radiotherapy. Assessment of toxicities and
      evaluationof response was carried out. RESULTS: Majority of patients had stage IV
      diseaseand 17/21 (81%) received the planned radiotherapydose of 70Gy and >=4
      cycles of weekly chemotherapy. Duration of treatment ranged from 7.1to 11.2
      weeks. The toxicities noted were Grade III mucositis in 57% and grade III skin
      reaction in 23%, grade III dysphagia in 38% and grade II weight loss in 23% of
      patients. Systemic toxicities associated with chemotherapy were minimal and there
      was no dose limiting toxicities. The overall locoregional response at first
      follow up was 85%, with complete response of 70% and partial response of 15%.
      CONCLUSION: Concurrent Docetaxel is a feasible and suitable alternate to
      Cisplatin and 5-Fluorouracil chemotherapy with good patient compliance. The late
      toxicities and survival need to be followed up.

PMID- 25954691
TI  - Pattern of cancer in a tertiary care hospital in malwa region of punjab, in
      comparison to other regions in India.
AB  - CONTEXT: Cancer pattern varies in different regions and depends on race,
      lifestyle and diet. There is a lack of definitive information regarding hospital
      based cancer profile in Southern Punjab, which is a cotton growing area. Excess
      of toxins in the macro-environment is thought to be the reason for the high
      incidence of cancer in this area. AIMS: To generate data on the magnitude and
      pattern of cancer cases reporting in the medical college hospital and to plan
      activities for prevention of cancer in the field practice area. SETTINGS AND
      DESIGN: A five year record-based retrospective study from 1(st)January 2007 to
      31(st)December 2011. MATERIALS AND METHODS: All cancer cases who reported either
      for diagnosis or for treatment (radiotherapy/chemotherapy/surgery) were included
      in the study. These confirmed cases of cancer were classified according to the
      International classification of Disease (ICD-10) given by WHO. STATISTICAL
      ANALYSIS: Descriptive statistics, percentages. RESULTS: Out of a total of 1328
      cancer cases, females accounted for 809 (60.9%) and males for 519 (39.1%) cases.
      Male to female ratio was 1:1.55. The maximum number of patients were seen in 35
      64 yr age group (63.5%). Top five leading sites of cancer in males were lung
      (9.6%), myeloid leukemia (8.3%), prostate (6.8%), mouth (6.1%) and gall bladder
      (6.0%); and in females were breast (35.7%), cervix (19.1%), esophagus (5.1%),
      myeloid leukemia (4.7%) and gall bladder (3.9%). Our figures have been compared
      with the national data from NCRP. CONCLUSION: Population-based epidemiological
      studies are required to find out the disease burden & its cause in this region.

PMID- 25954692
TI  - Integrative oncology in Indian subcontinent: an overview.
AB  - Integrative oncology is a combination of one where complementary and alternative
      medicine (CAM) with conventional cancer treatment modalities is used to manage
      symptoms, control side-effects and improve the state of mental wellbeing. The
      ancient Indian medicinal approach in cancer treatment and management has a wide
      array of herbs and practices. There is an increasing demand for traditional and
      natural medicine by the cancer patients. The conventional oncologic surgeons and
      physicians should be aware of the role of cCAM that are available in Indian
      subcontinent and provide a treatment that focuses on the physical and mental
      state of wellness in combating cancer. 

PMID- 25954693
TI  - "Ozone" - the new NEMESIS of canker sore.
AB  - BACKGROUND: Recurrent aphthous ulceration or recurrent aphthous stomatitis is one
      of the most debilitating and painful oral mucosal disease. This disease entity
      has no specific cause to occur and no proper laboratory procedures are present to
      elicit the diagnosis. The treatment options are largely palliative and aimed at
      reducing symptoms thereby improving patient's oral condition. In the present
      study the subjects witnessed alleviation of clinical symptoms related to the
      aphthous ulceration. AIMS AND OBJECTIVES: The aim of the study was to explore the
      effectiveness of ozonated oil in the treatment of recurrent aphthous ulcer and to
      compare with sessame oil in order to analyse the effectiveness between the two
      topical oil medications. MATERIALS AND METHODS: A single-blinded placebo
      controlled trial comprising of 30 subjects with recurrent aphthous ulcers were
      divided into Group 1, Group 2 and Group 3 with 10 subjects in each group was
      performed. Patients in Group 1 received ozonated oil, Group 2 received sesame oil
      and Group 3 received placebo. Treatment response was assessed by measures of pain
      reduction, ulcer duration on 2(nd), 4(th) and 6(th) day. Data were analyzed using
      Wilcokson signed rank test and Friedman test. RESULTS: Participants treated with
      ozonated oil showed significant reduction in ulcer size, erythema and also
      alleviated the ulcer pain on 4(th) day of evaluation when compared to sesame oil
      and placebo group. On 6(th) day subjects treated with ozonated oil and sesame oil
      showed significant reduction in ulcer size and erythema. No significant
      difference was observed in placebo group when compared with other two groups on
      subsequent 2(nd), 4(th) and 6(th) day of evaluation. CONCLUSION: Ozonated oil and
      sessame oil, both showed similar effectiveness in relieving the ulcer pain. Ozone
      with its wide variety of inherent properties has proven to be choice of treatment
      in completely relieving the ulcer pain and ulcer size when compared with that of
      its counter medication (i.e. sesame oil).Therefore the results obtained in the
      present study forecast ozone to be used as a novel treatment approach in
      recurrent aphthous ulcers.

PMID- 25954694
TI  - The influence of implant abutment surface roughness and the type of cement on
      retention of implant supported crowns.
AB  - OBJECTIVES: To provide relative data on the retentive characters of the commonly
      used cements on different implant abutment surfaces. MATERIALS AND METHODS: A
      total of 20 implant abutments were divided into 2 groups. Ten implants were
      unaltered and ten were air borne particle abraded with 50MU aluminium oxide.
      Three luting agents (Tempbond, IRM and ImProv) were used to secure the crowns to
      abutments. All the crowns were removed from the abutment with an Instron machine
      at 0.5mm per minute and tensile bond strengths were recorded. Statistical
      analysis was performed using Anova, Paired t-test and Post-Hoc tests. RESULTS:
      IRM showed the highest mean tensile strength among the three cements when used
      with treated and untreated implant abutment surfaces. Change in the abutment
      surface roughness had no effect on the mean tensile bond strength of TempBond and
      IRM cements, whereas ImProv cement showed reduced tensile strength with
      sandblasted surface. CONCLUSION: When increased retention is required IRM cement
      with either sandblasted or milled surface could be used and when retrievability
      is required cements of choice could be either TempBond or ImProv.

PMID- 25954695
TI  - Efficacy of Prophylactic use of Antibiotics to Avoid Flare up During Root Canal
      Treatment of Nonvital Teeth: A Randomized Clinical Trial.
AB  - OBJECTIVES: Flare-up during root canal treatment of non vital teeth is a common
      clinical incident. The aim of the present study was to assess the effect of
      prophylactic use of antibiotics to avoid flare up during root canal treatment of
      the teeth having asymptomatic necrotic pulp. MATERIALS AND METHODS: A randomized
      double blind clinical trial with parallel design was conducted on 100 subjects
      with asymptomatic non vital teeth. They were randomly divided into two groups.
      The first group (50 participants) was given two gram amoxicillin one hour before
      the first visit of root canal treatment; the second group (50 participants) did
      not receive any treatment (control group). In both groups, root canal treatment
      was performed in two visits. The flare up was assessed by the pain visual
      analogue scale and based on the swelling criteria. The data were processed and
      analyzed using SPSS statistical software 17. A p-value of 0.05 or less was
      considered statistically significant. RESULTS: A total of 80% of participants in
      the experimental group had flare up while 12% of participants had flare up in the
      control group. Prophylactic Amoxicillin had no effect on inter-appointment flare
      up (p > 0.05). There was no relationship between flare up and patient's age,
      gender and tooth type (p > 0.05). CONCLUSION: Prophylactic use of Amoxicillin in
      asymptomatic non vital teeth before root canal treatment had no effect on the
      incidence of flare-up.

PMID- 25954696
TI  - The effect on the flexural strength, flexural modulus and compressive strength of
      fibre reinforced acrylic with that of plain unfilled acrylic resin - an in vitro
      study.
AB  - AIM: The aim of this in vitro study was to compare the flexural strength, the
      flexural modulus and compressive strength of the acrylic polymer reinforced with
      glass, carbon, polyethylene and Kevlar fibres with that of plain unfilled resin.
      MATERIALS AND METHODS: A total of 50 specimens were prepared and divided into 10
      specimens each under 5 groups namely group 1- control group without any fibres,
      group 2 - carbon fibres, group 3- glass fibres, group 4 - polyethylene, group 5-
      Kevlar. Universal testing machine (Tinius olsen, USA) was used for the testing of
      these specimens. Out of each group, 5 specimens were randomly selected and
      testing was done for flexural strength using a three point deflection test and
      three point bending test for compressive strength and the modulus was plotted
      using a graphical method. Statistical analysis was done using statistical
      software. RESULTS: The respective mean values for samples in regard to their
      flexural strength for PMMA plain, PMMA+ glass fibre, PMMA+ carbon, PMMA+
      polyethylene and PMMA+ Kevlar were 90.64, 100.79, 102.58, 94.13 and 96.43
      respectively. Scheffes post hoc test clearly indicated that only mean flexural
      strength values of PMMA + Carbon, has the highest mean value. One-way ANOVA
      revealed a non-significant difference among the groups in regard to their
      compressive strength. CONCLUSION: The study concludes that carbon fibre
      reinforced samples has the greatest flexural strength and greatest flexural
      modulus, however the compressive strength remains unchanged.

PMID- 25954697
TI  - Comparative evaluation of fracture resistance of root obturated with resilon and
      gutta-percha using two different techniques: an in vitro study.
AB  - INTRODUCTION: Present study evaluated the fracture resistance of endodontically
      treated teeth filled with Gutta percha and a new resin based obturating material
      (Resilon). MATERIALS AND METHODS: A total of 150 freshly extracted Mandibular
      premolar with fully formed apices were selected and decoronated at cemento-enamel
      junction (CEJ). Teeth were divided into Group A and Group B of 75 teeth each. In
      Group A canals were prepared up to # no 40 K file and Group B up to #no 80 K
      file. Both the groups were sub divided into five group of 15 teeth each as
      control group (unfilled canals), lateral condensation with Gutta-percha using AH
      26 sealer, vertical condensation with Gutta-percha using AH 26 sealer, lateral
      condensation with Resilon using resilon sealer, vertical condensation with
      Resilon using resilon sealer. Each specimen was subjected to compressive load
      using Universal testing machine. The force required to fracture was recorded and
      data were analysed by ANOVA, Duncan's test and student T test. RESULT: The result
      showed that there is statistically significant difference among experimental
      groups (p < 0.05). The groups with the Resilon material displayed higher mean
      fracture loads than the Gutta percha groups. No statistically significant
      differences were observed between different preparation techniques. CONCLUSION:
      Obturating the canals with the new resin-based obturation material increases the
      in vitro fracture resistance of endodontically treated teeth when compared with
      standard Gutta percha techniques.

PMID- 25954698
TI  - Comparison of Two Brushing Methods- Fone's vs Modified Bass Method in Visually
      Impaired Children Using the Audio Tactile Performance (ATP) Technique.
AB  - BACKGROUND: To evaluate the effectiveness of two brushing techniques - Fone's
      method Vs Modified Bass method in visually impaired children using the Audio
      Tactile Performance (ATP) technique. SETTINGS AND DESIGN: Eighty
      institutionalised visually impaired children, aged between 4-15 y were randomly
      selected. MATERIALS AND METHODS: Baseline plaque scores were recorded using
      Silness and Loe plaque index. The subjects were then randomly divided into two
      groups of which, 40 were trained with Fone's method and and other 40 with
      Modified Bass method using the ATP technique. Plaque scores were evaluated again
      after two months. The effectiveness of oral hygiene maintenance in these children
      were analysed and evaluated statistically. STATISTICAL ANALYSIS: Data was
      analysed using Wilcoxon signed rank test and paired t-test. RESULTS: Both Fone's
      and Modified Bass method showed reduction in plaque which was statistically
      significant. There was an increase in the frequency of tooth brushing following
      training. CONCLUSION: The Fone's method and the Modified Bass method of tooth
      brushing showed a significant improvement in the oral hygiene of visually
      impaired children when taught using an effective communication tool, the ATP
      technique.

PMID- 25954699
TI  - Gingival, plasma and salivary levels of melatonin in periodontally healthy
      individuals and chronic periodontitis patients: a pilot study.
AB  - INTRODUCTION: Periodontal disease is an inflammatory condition affecting tooth
      supporting structures in which dysregulated immune response and oxidative stress
      mediate tissue destruction. Melatonin, the pineal gland hormone is a regulator of
      circadian rhythm, an antioxidant and an immunomodulator. Previous studies have
      shown lowered melatonin levels in saliva, plasma and gingival crevicular fluid
      (GCF) of patients with periodontal disease. Till date no study has assessed the
      melatonin levels in gingival tissues. MATERIALS AND METHODS: Five healthy
      individuals and 15 chronic periodontitis patients were recruited for this pilot
      study. 5ml of whole saliva, 2 ml peripheral blood and gingival tissue samples
      were obtained from each individual at 8.00 am in fasting state. Melatonin assay
      was performed with a commercially available ELISA kit. Statistical analysis was
      done to assess the difference in mean melatonin levels among the groups. RESULTS:
      No statistically significant difference was found in mean melatonin levels
      between healthy individuals and chronic periodontitis patients in saliva (p=.266)
      and plasma (p=.933) samples, whereas in gingival tissue samples (p=.015), the
      melatonin levels were significantly lowered in chronic periodontitis patients
      compared to healthy individuals. CONCLUSION: This study demonstrates the presence
      of melatonin in gingival tissue. Furthermore, melatonin levels are lowered in
      gingival tissues of chronic periodontitis patients.

PMID- 25954700
TI  - A Comparative Study of Clinical Parameters in Submerged and Non submerged
      Implants.
AB  - AIM: The aim of this study was to evaluate and compare the radiographic bone loss
      and soft tissue parameters around one stage and two stage implants. MATERIALS AND
      METHODS: Twenty four patients with submerged implants and twenty four patients
      with non submerged implants at the time of loading were assessed in this
      prospective cohort study. The soft tissue assessment included probing depth (PD),
      papilla index (PI), mucosal thickness (MT) and keratinized tissue (KG); another
      parameter assessed was the radiographic distance between the shoulder of the
      implant and alveolar crest evaluated at baseline (loading time) and 3,6 and 12
      months after loading in both groups.Data were analysed using repeated measures
      analysis of variance (ANOVA) and multiple comparisons were done using LSD method.
      RESULTS: The changes in the soft tissues including PD, KG, MT and PI had no
      significant differences in either group. The amount of bone loss 3 and 6 months
      after loading was significantly greater in one stage implants (0.93+/-0.45 mm at
      3months and1.45+/-0.58 mm at 6months, for one stage and 0.32+/-0.21 mm at 3months
      and 0.74+/-0.43 mm at 6 months for two stage group). But the change of this index
      12 months later was not significantly different between the two groups (1.87+/
      0.76mm for one stage and 1.65+/-0.59mm for two stage group). CONCLUSION: Based on
      the results of this study there is no difference in hard and soft tissue changes
      one year after loading of one or two stage implants.

PMID- 25954701
TI  - Effect of chicken egg shell powder solution on early enamel carious lesions: an
      invitro preliminary study.
AB  - AIM: To evaluate the remineralization potential of enamel surface lesion using
      chicken eggshell powder (CESP) solution. MATERIALS AND METHODS: Ten freshly
      extracted un-erupted third molars decoronated at cement-enamel junction (CEJ)
      used in this study. Each decoronated tooth was sectioned to get 4 samples of
      enamel blocks such that 40 blocks were obtained which were then subjected to
      demineralization protocol and grouped as: Group 1-untreated group, Group 2
      subsurface demineralization, Group 3-subsurface demineralization + 7 days CESP
      immersion, Group 4- subsurface demineralization + clinpro application. The
      samples were evaluated for X-ray fluorescence spectroscopy analysis,
      microhardness testing and atomic analyses using energy dispersive X-ray
      spectroscopy. The data were statistically analysed by using one-way ANOVA and
      Tukey - Kramer multiple comparison test. RESULTS: X-ray Fluorescence spectroscopy
      shows Calcium concentration of 98% and 0.46% of phosphate. Group 4 (Clinpro)
      shows the highest efficacy in enhancing the remineralization followed by Group 3
      (CESP). The results of atomic analyses showed that quantitative amounts of Ca
      weight % and P weight % is statistically greater for all the three groups except
      the demineralized group. CONCLUSION: CESP with higher calcium content can
      remineralise enamel surface lesion.

PMID- 25954702
TI  - An alternative maxillary sinus lift technique - sinu lift system.
AB  - OBJECTIVES: Maxillary sinus augmentation surgical techniques have evolved greatly
      allowing successful placement of dental implants in the atrophic posterior
      maxillary region. The purpose of the present study is to evaluate the clinical
      and radiological outcomes and postoperative morbidity of sinus floor elevation
      procedures performed using the minimally invasive surgical technique the Sinu
      lift system. MATERIALS AND METHODS: Sinus lift procedure was done using the sinu
      lift system by a transcrestal approach and bone augmentation was done on ten
      systemically healthy patients using beta- tricalcium phosphate and platelet rich
      plasma mix. The study was evaluated upto six months period with bone related
      parameters being assessed at base line using CT scan, OPG and after six months
      the results were analysed using SPSS Version 18.0 software (p < 0.01 (0.005).
      Wilcoxson signed rank sum test was used to correlate between preoperative and
      postoperative measurements. Implant placements were done at the desired area of
      sinus augmentation with a two year follow up. (Nobel Biocare, Nobel Biocare
      Holding AG, Zurich-Flughafen, Switzerland) Results: The augmented sites had a
      significant increase in the bone parameters at the desired grafted region. The
      mean gain in bone height as observed in CT Scan had revealed increased
      measurements from 5.80mm+/-0.98 to 10.20mm+/-1.68 at the sixth month evaluation.
      This was statistically significant (0.005). Clinically, no complications were
      observed during or after the surgical procedure. CONCLUSION: Within the
      limitations of this study, the Sinu lift system with a controlled working action
      resulted in high procedural success and this procedure may be an alternative to
      the currently used surgical methods.

PMID- 25954703
TI  - The Effect of Primer on Bond Strength of Silicone Prosthetic Elastomer to
      Polymethylmethacrylate: An in vitro Study.
AB  - INTRODUCTION: The aim of the study is to evaluate interfacial bond strength
      between silicone prosthetic elastomers and polymethylmethacrylate (PMMA).
      MATERIALS AND METHODS: Silicone elastomers were attached to PMMA and a total 120
      specimens were fabricated which were then subdivided into 12 sub-groups. Each
      sample was then subjected to laboratory test to determine the bond strength. The
      specimen of silicone elastomer bonded to acrylic of different surfaces was placed
      into universal testing machine (HOUNSFIELD HT-400) for "PEEL TEST". All the
      values obtained were tabulated and subjected to statistical analysis. RESULT: The
      bond strength of silicone elastomer to acrylic resin (TRAVELON) noticed highest
      (Mean 4.826 +/- 0.008 n/mm) when only primer was used as a surface treatment.
      When silicone elastomer bonded to acrylic resin (DPI) showed the bond strength of
      (4.351 +/- 0.0089) when only primer was used as a surface treatment. Whereas the
      least bond strength values were found when the silicone bonded to acrylic surface
      treated by 120 grit sand paper that is (0.076 +/- 0.00 n/mm) and (0.082 +/- 0.01
      n/mm) for DPI and TRAVELON respectively. CONCLUSION: The bond strength of
      silicone elastomer to acrylic resin was higher when primer was used on the
      acrylic surface. The bond strength of silicone elastomer to acrylic resin was
      more with travelon resin when compared to DPI resin. But when silicone was bonded
      to acrylic surface with sand papering, showed less bond strength.

PMID- 25954704
TI  - A Comparative SEM Investigation of Smear Layer Remaining on Dentinal Walls by
      Three Rotary NiTi Files with Different Cross Sectional Designs in Moderately
      Curved Canals.
AB  - OBJECTIVE: The objective of this study was to compare the smear layer formed on
      root canal walls during canal preparation of extracted human teeth by Twisted,
      Mtwo, and ProTaper rotary nickel titanium instruments. MATERIALS AND METHODS:
      Sixty single rooted human premolar teeth with root curvature <25(0) were selected
      and randomly divided into three Groups (n= 20 teeth per Group). Three types of
      rotary nickel titanium instruments were used, Twisted (SybronEndo, Orange, CA,
      USA), Mtwo (VDW, Munich, Germany) and ProTaper (Dentsply Maillefer, Ballaigues,
      Switzerland) according to manufacturer's instructions to instrument the root
      canals. Irrigation for all groups was performed after each instrument change with
      3ml of 3% sodium hypochlorite followed by Glyde (File Prep, Dentsply, Maillefer,
      Ballaigues, Switzerland) as chelator paste and lubricant. Three different areas
      (coronal, middle and apical thirds) of the root canal were evaluated using
      scanning electron microscopy (SEM). The canal wall of each sample was assessed
      and compared using a predefined scale for the presence or absence of smear layer.
      Data were analysed statistically using ANOVA and Tukey HSD test Results: All
      three groups showed statistically significant more smear layer in the apical
      thirds of the canal as compared to the coronal and middle thirds (p<0.001). Mtwo
      rotary file system produced significantly less smear layer (p<0.001) compared to
      Twisted and ProTaper rotary instruments in the apical portion. Twisted Files
      resulted in less smear layer formation in the apical thirds of the canal compared
      to ProTaper rotary instruments but were statistically insignificant. CONCLUSION:
      Completely clean root canals were not found after instrumentation with any of the
      three instruments. Under the confines of this study Mtwo instruments produced
      significantly cleaner dentin wall surfaces throughout the canal length in
      comparison to Twisted and ProTaper rotary files. Twisted Files proved to be
      comparable to ProTaper rotary instruments with respect to canal cleanliness in
      the apical thirds of the root canal.

PMID- 25954705
TI  - Comparative Evalution of G bone (Hydroxyapatite) and G-Graft (Hydroxyapatite with
      Collagen) as Bone Graft Material in Mandibular III Molar Extraction Socket.
AB  - BACKGROUND: Bone grafting is a dynamic phenomenon. It is a surgical procedure
      that replaces missing bone with material either from patient's own body, or, an
      artificial, synthetic or natural substitute. A successful bone graft when
      applied, heals, becomes incorporated, re-vascularises and eventually assumes the
      form desired. AIMS AND OBJECTIVE: The main purpose of this present study was to
      radiologically assess and compare the regenerative potential of hydroxyapatite
      with Collagen (G-Graft) and hydroxyapatite (G-Bone) and to evaluate the clinical
      usefulness of these materials to enhance bone healing in third molar extraction
      sites through bone formation. MATERIALS AND METHODS: The study was carried out in
      the Department of Oral & Maxillofacilal Surgery, patients were divided into three
      groups. The rationale for assigning the patients to the groups was strictly
      random: Group I - G-Graft (Hydroxyapatite with Collagen) was used as Bone graft
      material, Group II - Bone graft material used was G-Bone (Hydroxyapatite), Group
      III-control group (no grafts was used). Orthopentomogram(OPG) images were taken
      intra-operatively, just after extraction in the Group III (control), after
      extraction but before graft placement in Group I & II (study groups) and post
      operatively at the end of first month and third month. Bone density of the post
      extraction sockets was measured at four random areas through 'densitometric
      analysis' software in the OPG program (Kodak 8000C Digital Panoramic System,
      Eastman Kodak Company) and an average value was recorded at each review. RESULTS:
      The percentage increase in bone density between 1(st) month & 3(rd) month was
      7.55+/- 12.43 in Group I (G Graft), 4.41+/- 5.4859 in Group II (G Bone), while
      that Group III (control) was found to be -0.82 +/- 3.96. The bone density
      increase was found to be statistically highly significant (p<0.01)) between all
      groups. CONCLUSION: The present study concluded that G-Graft has a definite
      regenerative potential and is better than G-bone and can be used in bony defects
      to enhance the bone healing without provoking any significant inflammatory
      process. The study also indicates that defects treated with G-Graft attain more
      density initially and that G-Graft enhances bone healing in early stage.

PMID- 25954706
TI  - Periodontal Status Among Patients With Cleft Lip (CL), Cleft Palate (CP) and
      Cleft Lip, Alveolus and Palate (CLAP) In Chennai, India. A Comparative Study.
AB  - BACKGROUND: Long term health of the stomatognathic system as well as esthetic
      aspects is the therapeutic goals in patients with oro facial clefts. AIM: The aim
      of this study was to assess and compare the periodontal status of patients with
      cleft lip (CL), cleft palate (CP) and cleft lip, alveolus and palate (CLAP)
      reporting to a hospital in Chennai, India. MATERIALS AND METHODS: The study group
      consisted of 80 cleft patients. Subjects were divided into three groups. Group 1:
      patients with cleft lip (CL), Group 2: subjects with cleft palate (CP) and Group
      3: subjects with cleft lip alveolus and palate (CLAP). Community Periodontal
      Index for Treatment needs CPITN Index was recorded. RESULTS: Among the 80 study
      subjects, 51 (63.8%) were males and 29 (36.2%) were females. Among the 26 study
      subjects with cleft lip, 10 (38.5%) had healthy periodontium, 4 (15.4%) had
      bleeding on probing and 12 (46.1%) had calculus. Mean number of sextants coded
      for healthy and bleeding was maximum among the subjects with cleft palate. Mean
      number of sextants coded for calculus was maximum among the subjects with cleft
      lip alveolus and palate. Prevalence of periodontal disease is high among patients
      with cleft lip, alveolus and palate (35%) than in Cleft lip (32.5%) and Cleft
      Palate (32.5%). CONCLUSION: Gingivitis and Calculus is predominantly high in
      patients with Cleft Palate and Cleft Lip respectively.

PMID- 25954707
TI  - Evaluation of variation in the palatal gingival biotypes using an ultrasound
      device.
AB  - BACKGROUND: The dimensions of gingiva and different parts of the masticatory
      mucosa have become a subject of considerable interest in Periodontics. Studies
      assessing the thickness of the facial gingiva are often seen in the literature.
      The thickness of the palatal gingiva is a subject still less researched in
      periodontal therapy and implantology. OBJECTIVES: To measure the thickness of the
      palatal gingiva using an ultrasound device 'Biometric A- Scan' and to evaluate
      the variation in the thickness of the palatal gingiva at the sites examined.
      MATERIALS AND METHODS: In the 50 subjects examined, the thickness of the palatal
      gingiva was assessed at the maxillary anteriors, premolars and molars by an
      ultrasound device 'Biometric A-Scan'. The results were subjected to statistical
      analysis using one-way ANOVA test and Newman-Keuls multiple post hoc procedure.
      RESULTS: Statistically significant variations existed in the palatal gingival
      thickness. The thickness was highest at the lateral incisor region, followed by
      canine, premolars, molars and central incisor. INTERPRETATION AND CONCLUSION: In
      the subjects assessed, the thickness of the palatal gingiva at the lateral-canine
      area was the highest followed by the premolar area. In periodontal root coverage
      procedures and during implant therapy, we suggest the inclusion of the lateral
      incisor area, apart from the canine and premolar area, as a potential donor site
      for harvesting soft tissue grafts from the palatal area. However, the effect of
      several factors like age and sex of the patient, the anatomy of the palatal area,
      the influence of rugae patterns and racial and geographical differences should be
      taken into consideration prior to harvesting a graft from these sites. Apart from
      this, the study suggests that, the ultrasonographic measurements provide an
      elegant means of obtaining the measurements of gingival and mucosal tissues
      rapidly, accurately and non-invasively. Our endeavour in this research project
      attempts to open more avenues for studies in the field of advanced periodontal
      diagnosis, with the use of ultrasound, and expand the horizons of periodontal
      plastic surgery and implant therapy as well.

PMID- 25954708
TI  - Intraosseous schwannoma of the maxilla mimicking a periapical lesion: a
      diagnostic challenge.
AB  - Schwannomas are a type of nerve sheath tumours predominant in the soft tissues of
      the head and neck. They commonly present as slow growing, painful swellings and
      may rarely be accompanied by paresthesia. Less than 1% of schwannomas are
      intraosseous with affliction to the mandible over maxilla. Only 13 cases of
      maxillary schwannomas have been reported till date. This article documents a rare
      case of intramaxillary schwannoma that was disclosed during an incidental
      radiographic examination. It also provides a review of the literature on central
      schwannomas affecting the maxilla which suggests its affliction to females in the
      second decade with equal preference to both anterior and posterior segments of
      the jaw. It also highlights that intraosseous schwannomas may be considered in
      the differential diagnosis of periapical lesions with nonspecific clinical and
      radiographic features. 

PMID- 25954709
TI  - Keratoameloblastoma a rare entity: a case report.
AB  - Ameloblastoma is the second most common odontogenic tumour of oral cavity; which
      has several different histological variants such as follicular, plexiform,
      acanthomatous, granular cell, desmoplastic, basal cell, clear cell,
      hemangiomatous, mucous cell differentiation and keratoameloblastoma. It is common
      in posterior mandible and has high male predilection in the ratio of 3:1. This
      report presents a case of keratoameloblastoma in 65-year-old female patient in
      the anterior mandible region with literature review on clinical features,
      histopathological findings, radiological appearance and treatment options. 

PMID- 25954710
TI  - Resection and Regeneration - A Novel Approach in Treating a Perio-endo Lesion.
AB  - The pulp and the periodontium are invariably anatomically and functionally
      related to each other. Lesions involving both the periodontium and the pulp
      complicate diagnosis, treatment planning and prognosis. An emerging approach to
      periodontal therapy is the concept of regeneration. In this case report, a novel
      combination therapy of a blend of platelet rich fibrin with bone graft and guided
      tissue regeneration membrane was used in the treatment of a perio-endo lesion of
      a multirooted tooth. A successful outcome in alleviating patient's symptoms and
      regeneration was seen. 

PMID- 25954711
TI  - Idiopathic leukoplakia- report of a rare case and review.
AB  - Idiopathic leukoplakia is a rare potentially malignant lesion, usually found on
      the tongue with an increased risk of malignant transformation as compared to the
      tobacco associated form. The risk of malignant transformation increases with age.
      Diagnosis poses a challenge to the clinician as it is diagnosed by exclusion of
      other possible causes leading to hyperkeratosis. We present one such rare case in
      an elderly male patient who was followed up for a year to record the course of
      the lesion and to report recurrences, if any. 

PMID- 25954712
TI  - Myxosarcoma of the maxilla - a case report.
AB  - Myxosarcoma is a rare malignant neoplasm of connective tissue which is
      characterized by tissue that resembles primitive mesenchyme, and contains
      relatively undifferentiated cells that show rapid growth and invasion. The cells
      are stellate or spindle-shaped and are present in a loose matrix which contains
      mucoid material, reticulum, and collagen fibers. This paper reports a rare case
      of a myxosarcoma of the left maxilla in a 50-year-old male, which clinically
      presented as a soft-tissue mass on the buccal gingiva and radiographically showed
      a mixed radiolucent-radiopaque appearance. 

PMID- 25954713
TI  - Vanishing roots: first case report of idiopathic multiple cervico-apical external
      root resorption.
AB  - Idiopathic root resorption is a very rare phenomenon. Resorption in tooth is
      brought about by odontoclastic activity. Special mechanisms in the periodontal
      ligament exist to prevent mineralization of the periodontal ligament and these
      periodontal ligament cells produce factors that inhibit mineralized tissue
      resorption and are capable of regulating bone and cementum formation. When this
      mechanism is disturbed it manifests in resorption of root structure. This case
      report is of a 28-year-old male with a very rare phenomenon where external
      resorption of both cervical and apical portion of root of multiple teeth was
      observed and it is documented for the first time. 

PMID- 25954714
TI  - Ameloblastomatous calcifying cystic odontogenic tumour: a rare variant.
AB  - Calcifying Cystic Odontogenic Tumor (CCOT) was previously described by Gorlin et
      al., in 1962 as Calcifying odontogenic cyst. CCOT is a rare lesion which accounts
      for 2% of all odontogenic pathological changes in the jaws. One of the variants,
      Ameloblastomatous proliferating type of CCOT is even more rare and very few cases
      have been reported in the light of literature review. This case report is an
      effort to bring forth a case of ameloblastomatous proliferating type of CCOT in a
      65 year male, who presented with a painful swelling in the right jaw crossing
      midline causing facial asymmetry and confirmed by histopathological evaluation. 

PMID- 25954715
TI  - Solitary extragnathic langerhans cell histiocytosis - a rare case.
AB  - Langerhans cell histiocytosis (LCH), mainly affects the skull, vertebrae, ribs
      and mandible in children and the long bones of adults. Symptoms range from none
      to pain, swelling and tenderness over the site of the lesion. This disease
      presents oral manifestations which can sometimes be the first expression of the
      condition. It occurs in three forms namely eosinophilic granuloma in which
      isolated or multiple bones are involved, But has a good prognosis whereas other
      variants Hand-Shuller-Christian disease (chronic dessiminated variant) and
      Letterer-Siwe disease (acute dessiminated form) have poor prognosis. Occasionally
      only soft tissues are affected without bony involvement. Males are more commonly
      affected than females. This article describes a rare variant of eosinophilic
      granuloma of labial mucosa without bony involvement. 

PMID- 25954716
TI  - Pressure alteration techniques in endodontics- a review of literature.
AB  - The triad of biomechanical preparation, pulp space sterilization and three
      dimensional obturation is the hallmark of endodontic success. Complete
      disinfection of the pulp space cannot be achieved with most sophisticated
      instrumentation techniques. The role of irrigants in obtaining this goal cannot
      be underestimated. Optimal irrigation is based on the combined use of two or
      several irrigating solutions, in a specific sequence. Today's irrigation
      armamentarium presents a diverse variety of tools and techniques that can assist
      the practitioner in reducing bacteria and debris within the canal system.
      However, currently there is no universally accepted standard irrigation
      technique. The aim of this article is to review armamentarium and various
      irrigants in endodontic practice. 

PMID- 25954717
TI  - SHED - Basic Structure for Stem Cell Research.
AB  - The discovery that stem cells from dental pulp are capable of differentiating
      into endothelial cells raised the exciting possibility that these cells can be a
      single source of odontoblasts and vascular networks in dental tissue engineering.
      These so-called mesenchymal stem cell populations have been identified from human
      exfoliated deciduous teeth because of their ability to generate clonogenic
      adherent colonies when grown and expanded. In addition to these stem cells, other
      population of stem cells can be from adult human dental pulp and periodontal
      ligament. The identification and isolation of these stem cells in adult dental
      pulp was first reported by Gronthos and co-workers in 2000.These dental pulp stem
      cells have clonogenic abilities, rapid proliferative rates and the capacity to
      form mineralized tissues both in vitro and in vivo. The stem cells from human
      exfoliated deciduous teeth are distinct from dental pulp stem cells by virtue of
      their proliferation rate, increased cell population doublings and osteoinductive
      capacity in vivo. It is further demonstrated that human exfoliated deciduous
      teeth stem cells may not be a single-cell type, may well be a heterogenous
      population of cells from the pulp. 

PMID- 25954718
TI  - Angulated implants: an alternative to bone augmentation and sinus lift procedure:
      systematic review.
AB  - Rehabilitation of completely edentulous patients with implant becomes challenging
      due to reduced amount of bone available and pneumatisation of maxillary sinus or
      both. To successfully treat such patients, prior to implant placement, patient
      has to undergo invasive procedures like sinus lift and/or bone augmentation which
      is not possible many time due to many reasons. This article focuses on an
      alternative treatment procedure in which two posterior implants are placed at an
      angle and two anterior implants are placed axially thereby eliminating the need
      for sinus lift or bone augmentation procedures. This article broadly discusses
      this "All on Four" concept in all aspects, its effects on bone, prosthesis
      survival, forces acting etc along with various related studies. 

PMID- 25954719
TI  - Myoepithelial Cells (MEC) of the Salivary Glands in Health and Tumours.
AB  - Myoepithelial cells (MEC) are found in the secretory units of many mammalian
      exocrine glands such as mammary, sweat, lacrimal and salivary glands. They are
      interposed between the secretory cells and the basal lamina.
      Immunohistochemically they are found to contain keratin intermediate filaments
      and are, therefore, considered to have an epithelial origin but at the same time
      they contain a large number of myofilaments which represent a massive expression
      of contractile proteins such as actin, myosin, calponin and caldesmon. Thus have
      smooth muscle like property also and hence the name. Numerous functions of MEC
      have been described, the most important of them being important for contraction
      of the glands and recently it has been found to prevent tumour progression. It
      should be noted that the diversity in the occurrence and dilemma regarding the
      pathogenesis of salivary gland tumours is due to lack in uniformity regarding the
      cells participating in its oncogenesis, especially the MEC. Also proper and
      extensive studies regarding MEC are very limited and thus have posed difficulty
      for a pathologist to understand this cell. In this review we try to bring about a
      thorough description of this cell in both physiological and pathological aspects.

PMID- 25954720
TI  - An interesting review on soft skills and dental practice.
AB  - In today's world of education, we concentrate on teaching activities and academic
      knowledge. We are taught to improve our clinical skills. Soft skills refer to the
      cluster of personality traits, social graces, and personal habits, facility with
      language, friendliness and personal habits that mark people to varying degrees.
      Soft Skills are interpersonal, psychological, self-promoted and non-technical
      qualities for every practitioner and academician, whereas hard skills are new
      tools or equipment and professional knowledge. Hence, more and more clinicians
      now days consider soft skills as important job criteria. An increase in service
      industry and competitive practices emphasizes the need for soft skills. Soft
      Skills are very important and useful in personal and professional life. 

PMID- 25954721
TI  - Super odontoma - a destructive swarm entity.

PMID- 25954722
TI  - Paget's Disease in Mandible: A Rare Occurrence in an Indian Sub-Continent.

PMID- 25954723
TI  - Prompt diagnosis and management of cervical necrotizing fascitis.

PMID- 25954724
TI  - Carotid artery calcification and sailolith in partially edentulous patient: an
      accidental finding on panoramic radiograph.

PMID- 25954725
TI  - Transit fixatives: an innovative study.
AB  - BACKGROUND: Universally accepted fixative is 10% formalin which has been used for
      preserving the tissues and their architecture. In certain conditions, formalin
      might not be readily available for immediate fixation. We here by explore more
      economical, eco-friendly and easily available solutions that can be used as
      transit media/ transporting media for tissue specimens. MATERIALS AND METHODS:
      The study included commonly available solutions like Spirit, Saline, Betadine
      solution, Hydrogen peroxide (H2O2), Local anesthesia (L.A), Rose water, Coconut
      oil, Coconut water, Ice cold water, Honey and Milk while keeping formalin as
      control. The fresh tissue sample was cut into multiple bits and placed in
      different containers for a period of 8 hours before transferring to formalin
      solution. CONCLUSION: Transit fixatives are very important in certain situations
      where formalin is not readily available. These fixatives can be used to fix the
      tissues for a period of at least 8 hours without causing any damage or distortion
      before they are fixed in formalin solution.

PMID- 25954726
TI  - Simple way of recording dental arch forms.
AB  - Like finger prints each individual has a unique dental arch form design.
      Recording patient's dental arch form may be required in various fields in
      dentistry be it longitudinal studies for evaluating growth, forensic dentistry
      and most importantly in orthodontic practice for fabricating arch wires for
      individual patients. An easy and practical method to obtain individual arch form
      for each patient is explained. 

PMID- 25954728
TI  - Development of job standards for clinical nutrition therapy for dyslipidemia
      patients.
AB  - Dyslipidemia has significantly contributed to the increase of death and morbidity
      rates related to cardiovascular diseases. Clinical nutrition service provided by
      dietitians has been reported to have a positive effect on relief of medical
      symptoms or reducing the further medical costs. However, there is a lack of
      researches to identify key competencies and job standard for clinical dietitians
      to care patients with dyslipidemia. Therefore, the purpose of this study was to
      analyze the job components of clinical dietitian and develop the standard for
      professional practice to provide effective nutrition management for dyslipidemia
      patients. The current status of clinical nutrition therapy for dyslipidemia
      patients in hospitals with 300 or more beds was studied. After duty tasks and
      task elements of nutrition care process for dyslipidemia clinical dietitians were
      developed by developing a curriculum (DACUM) analysis method. The developed job
      standards were pretested in order to evaluate job performance, difficulty, and
      job standards. As a result, the job standard included four jobs, 18 tasks, and 53
      task elements, and specific job description includes 73 basic services and 26
      recommended services. When clinical dietitians managing dyslipidemia patients
      performed their practice according to this job standard for 30 patients the job
      performance rate was 68.3%. Therefore, the job standards of clinical dietitians
      for clinical nutrition service for dyslipidemia patients proposed in this study
      can be effectively used by hospitals. 

PMID- 25954727
TI  - Carbohydrates and endothelial function: is a low-carbohydrate diet or a low
      glycemic index diet favourable for vascular health?
AB  - Low-carbohydrate diets have become increasingly popular in both media and
      clinical research settings. Although they may improve some metabolic markers,
      their effects on arterial function remain unclear. Endothelial dysfunction is the
      well-established response to cardiovascular risk factors and a pivotal feature
      that precedes atherosclerotic diseases. It has been demonstrated that a high
      carbohydrate-induced hyperglycemia and subsequent oxidative stress acutely worsen
      the efficacy of the endothelial vasodilatory system. Thus, in theory, a
      carbohydrate restricted diet may preserve the integrity of the arterial system.
      This review attempts to provide insight on whether low-carbohydrate diets have a
      favorable or detrimental impact on vascular function, or it is perhaps the
      quality of carbohydrate that should direct dietary recommendations. Research to
      date suggests that diets low in carbohydrate amount may negatively impact
      vascular endothelial function. Conversely, it appears that maintaining
      recommended carbohydrate intake with utilization of low glycemic index foods
      generates a more favorable vascular profile. Understanding these relationships
      will aid in deciphering the diverging role of modulating quantity and quality of
      carbohydrates on cardiovascular risk. 

PMID- 25954729
TI  - Dietary intake assessment and biochemical characteristics of blood and urine in
      patients with chronic gastritis.
AB  - Chronic gastritis is a prevalent gastroentestinal disease in Korea. The purpose
      of this study was to investigate status of foods and nutrients intake and health
      related biochemical indicators in the patients with chronic gastritis. Daily food
      and nutrient intake, blood lipids, and antioxidant indicators in the urine, were
      compared between a group of 19 patients diagnosed with chronic gastritis and a
      control group of 27 subjects having normal gastroscopy. No significant
      differences were found in age, height, weight, body mass index, and blood
      pressure between the two groups. Daily energy intakes were 1900.6 kcal for the
      chronic gastritis patient group, and 1931.8 kcal for the normal control group
      without significant difference. No significant difference was found between the
      two groups in all nutrient intakes except for cholesterol. The chronic gastritis
      patients consumed lower amount of sugars and sweeteners but greater amount of
      starchy food groups such as potatoes and legumes than subjects of control group
      consumed. Also the chronic gastritis patients showed higher serum triglyceride
      concentration than the normal subjects. These results indicate that the dietary
      pattern of chronic gastritis patients may have relation to a change in the serum
      lipid level; however, more systematic research with a larger samples size is
      required. 

PMID- 25954730
TI  - Glycated Hemoglobin is a Better Predictor than Fasting Glucose for
      Cardiometabolic Risk in Non-diabetic Korean Women.
AB  - This study aimed to investigate if glycated hemoglobin (HgbA1C) as compared to
      fasting blood glucose is better for reflecting cardiometabolic risk in non
      diabetic Korean women. Fasting glucose, HgbA1C and lipid profiles were measured
      in non-diabetic women without disease (n = 91). The relationships of fasting
      glucose or HgbA1C with anthropometric parameters, lipid profiles, and liver and
      kidney functions were analyzed. Both fasting glucose and HgbA1C were negatively
      correlated with HDL-cholesterol (r = -0.287, p = 0.006; r = -0.261, p = 0.012),
      and positively correlated with age (r = 0.202, p = 0.008; r = 0.221, p = 0.035),
      waist circumference (r = 0.296, p = 0.005; r = 0.304, p = 0.004), diastolic blood
      pressure (DBP) (r = 0.206, p = 0.050; r = 0.225, p = 0.032), aspartate
      transaminase (AST) (r = 0.237, p = 0.024; r = 0.368, p < 0.0001), alanine
      transaminase (ALT) (r = 0.296, p = 0.004; r = 0.356, p = 0.001), lipid profiles
      including triglyceride (r = 0.372, p < 0.001; r = 0.208, p = 0.008), LDL
      cholesterol (r = 0.315, p = 0.002; r = 0.373, p < 0.0001) and total cholesterol
      (r = 0.310, p = 0.003; r = 0.284, p = 0.006). When adjusted for age and body mass
      index, significant relationships of DBP (r = 0.190, p = 0.049), AST (r = 0.262, p
      = 0.018), ALT (r = 0.277, p = 0.012), and HDL-cholesterol (r = -0.202, p = 0.049)
      with HgbA1C were still retained, but those with fasting glucose disappeared. In
      addition, the adjusted relationships of LDL-cholesterol and total cholesterol
      with HgbA1C were much greater than those with fasting glucose. These results
      suggest that glycated hemoglobin may be a better predictor than fasting glucose
      for cardiometabolic risk in non-diabetic Korean women. 

PMID- 25954731
TI  - Weight gain in pregnancy, maternal age and gestational age in relation to fetal
      macrosomia.
AB  - To investigate the possible risk factors related to macrosomia. Pregnant women
      and their newborns (n = 1041) were recruited from a cohort study in Maternal and
      Child Care Center of Hefei from January 2011 to July 2012. Questionnaires were
      applied to collect the demographic data besides the medical records. Detailed
      health records of the entire pregnancy were obtained using retrospective study.
      Meanwhile the data of neonatal outcomes was prospectively tracked. Associations
      between exposure risk factors and macrosomia were analyzed using Pearson's chi
      squared test. Logistic regression models were used to assess the independent
      association between these potential predictors and macrosomia. The incidence of
      macrosomia of this cohort was 11.24% of which male: female = 2.55:1. Male
      incidence (8.07%) of macrosomia was higher than female (3.17%), p < 0.001. Body
      mass index (BMI) before pregnancy (pre-BMI), maternal height, parity were not
      independently associated with macrosomia; multiple logistic regression analysis
      indicated that macrosomia was mainly independently associated with weight gain in
      pregnancy (OR=1.14, 95% CI [1.10-1.19]), maternal age (OR = 1.09, 95% CI [1.03
      1.15]) and gestational age (OR = 1.62, 95% CI [1.31-1.99]), respectively. Our
      findings indicate that weight gain in pregnancy, maternal age and gestational age
      should be considered as independent risk factors for macrosomia. 

PMID- 25954732
TI  - Associations of colorectal cancer incidence with nutrient and food group intakes
      in korean adults: a case-control study.
AB  - This study aimed to examine the associations between intakes of various nutrients
      and food groups and colorectal cancer risk in a case-control study among Koreans
      aged 20 to 80 years. A total of 150 new cases and 116 controls were recruited
      with subjects' informed consent. Dietary data were collected using the food
      frequency questionnaire developed and validated by the Korea Centers for Disease
      Control and Prevention. Multivariate logistic regression models were used to
      estimate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for
      colorectal cancer incidence. High intakes of total lipid (ORT3 vs T1 = 4.15, 95%
      CI: 1.33-12.96, p for trend = 0.034), saturated fatty acid (ORT3 vs T1 = 2.96,
      95% CI: 1.24-7.04, p for trend = 0.016) and monounsaturated fatty acid (ORT3 vs
      T1 = 3.04, 95% CI: 1.23-7.54, p for trend = 0.018) were significantly associated
      with increased incidence of colorectal cancer. High dietary fiber (ORT3 vs T1 =
      0.22, 95% CI: 0.08-0.56, p for trend = 0.002) and vitamin C (ORT3 vs T1 = 0.38,
      95% CI: 0.14-1.05, p for trend = 0.021) intakes were significantly associated
      with reduced colorectal cancer incidence. From the food group analysis, bread
      (ORT3 vs T1 = 2.26, 95% CI: 0.96-5.33, p for trend = 0.031), red meat (ORT3 vs T1
      = 7.33, 95% CI: 2.98-18.06, p for trend < 0.001), milk.dairy product (ORT3 vs T1
      = 2.42, 95% CI: 1.10-5.31, p for trend = 0.071) and beverage (ORT3 vs T1 = 3.17,
      95% CI: 1.35-7.48, p for trend = 0.002) intakes were positively associated with
      colorectal cancer risk. On the other hand, high intake of traditional rice cake
      (ORT3 vs T1 = 0.35, 95% CI: 0.14-0.86, p for trend = 0.024) was linked with lower
      colorectal cancer incidence. In conclusion, eating a diet high in total lipid,
      saturated fatty acids and monounsaturated fatty acids is associated with higher
      incidence of colorectal cancer, whereas a diet high in dietary fiber and vitamin
      C was found to lower the incidence in Korean adults. Interestingly high
      traditional rice cake consumption is associated inversely with colorectal cancer
      incidence, warranting a future study. 

PMID- 25954733
TI  - Efficacy of Cistanche Tubulosa and Laminaria Japonica Extracts (MK-R7) Supplement
      in Preventing Patterned Hair Loss and Promoting Scalp Health.
AB  - Cistanche tubulosa and Laminaria japonica have been reported to have anti
      oxidative, anticoagulant, anti-cancer and anti-inflammatory properties. They are
      expected to be a promising candidates for promoting hair growth and treating
      dandruff and scalp inflammation as a consequence. In this double-blinded, placebo
      controlled clinical trial, we investigated the efficacy of Cistanche tubulosa
      extract and Laminaria japonica extract complex (MK-R7) in promoting hair health
      in patients with mild to moderate patterned hair loss. Using phototrichogram
      (Folliscope 4.0, LeadM, Seoul, Korea), we compared the density and diameter of
      hairs in patients receiving a placebo or Cistanche tubulosa extract and Laminaria
      japonica extract complex (MK-R7) at baseline, 8 and 16 weeks of the study. In
      order to determine the efficacy of treatment on dandruff and scalp inflammation,
      investigator's assessment score and patient's subjective score were also
      performed. We found a statistically significant increase in the hair density of
      the test group (n = 45, MK-R7 400 mg) after 16 weeks of consuming the MK-R7 (test
      group: 23.29 n/cm(2) +/- 24.26, control: 10.35 n/cm(2) +/- 20.08, p < 0.05). In
      addition, we found a statistically significant increase in hair diameter in the
      test group compared to control group at week 16 (test group: 0.018 mm +/- 0.015,
      control: 0.003 mm +/- 0.013, p < 0.05). There were also significant outcomes
      regarding the investigator's visual assessment and patient's subjective score of
      dandruff and scalp inflammation in the test group compared to those in control
      group. Based on the results of this clinical study, we conclude that Cistanche
      tubulosa extract and Laminaria japonica extract complex (MK-R7) are promising
      substances for promoting health of the scalp and hair. 

PMID- 25954734
TI  - Nutrition Therapy for Mitochondrial Neurogastrointestinal Encephalopathy with
      Homozygous Mutation of the TYMP Gene.
AB  - Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is characterized by
      significant gastrointestinal dysmotility. Early and long-term nutritional therapy
      is highly recommended. We report a case of MNGIE in a patient who was undergoing
      long-term nutrition therapy. The patient was diagnosed with a serious symptom of
      fatty liver and hyperlipidemia complications, along with homozygous mutation of
      the thymidine phosphorylase (TYMP) gene (c.217G > A). To our knowledge, this is
      the first report of such a case. Herein, we describe preventive measures for the
      aforementioned complications and mitochondrial disease-specific nutritional
      therapy. 

PMID- 25954735
TI  - Corrigendum: "glia and neurodevelopment: focus on fetal alcohol spectrum
      disorders".
AB  - [This corrects the article on p. 123 in vol. 2, PMID: 25426477.]. 

PMID- 25954736
TI  - The influence of pre-operative hormonal stimulation on hypospadias repair.
AB  - Androgen stimulation to temporarily promote penile growth has been commonly used
      to facilitate hypospadias repair. Although some series suggest improvement in
      both functional and cosmetic outcomes, a recent systematic review and meta
      analysis showed a possible relationship between pre-operative hormonal
      stimulation and higher complications. As a result, indications and treatment
      regimens remain controversial. Here, we review the available literature and
      present our clinical practice. 

PMID- 25954737
TI  - Three-weekly doses of azithromycin for indigenous infants hospitalized with
      bronchiolitis: a multicentre, randomized, placebo-controlled trial.
AB  - BACKGROUND: Bronchiolitis is a major health burden in infants globally,
      particularly among Indigenous populations. It is unknown if 3 weeks of
      azithromycin improve clinical outcomes beyond the hospitalization period. In an
      international, double-blind randomized controlled trial, we determined if 3 weeks
      of azithromycin improved clinical outcomes in Indigenous infants hospitalized
      with bronchiolitis. METHODS: Infants aged <=24 months were enrolled from three
      centers and randomized to receive three once-weekly doses of either azithromycin
      (30 mg/kg) or placebo. Nasopharyngeal swabs were collected at baseline and 48 h
      later. Primary endpoints were hospital length of stay (LOS) and duration of
      oxygen supplementation monitored every 12 h until judged ready for discharge.
      Secondary outcomes were: day-21 symptom/signs, respiratory rehospitalizations
      within 6 months post-discharge and impact upon nasopharyngeal bacteria and virus
      shedding at 48 h. RESULTS: Two hundred nineteen infants were randomized (n = 106
      azithromycin, n = 113 placebo). No significant between-group differences were
      found for LOS (median 54 h for each group, difference = 0 h, 95% CI: -6, 8; p =
      0.8), time receiving oxygen (azithromycin = 40 h, placebo = 35 h, group
      difference = 5 h, 95% CI: -8, 11; p = 0.7), day-21 symptom/signs, or
      rehospitalization within 6 months (azithromycin n = 31, placebo n = 25 infants, p
      = 0.2). Azithromycin reduced nasopharyngeal bacterial carriage (between-group
      difference 0.4 bacteria/child, 95% CI: 0.2, 0.6; p < 0.001), but had no
      significant effect upon virus detection rates. CONCLUSION: Despite reducing
      nasopharyngeal bacterial carriage, three large once-weekly doses of azithromycin
      did not confer any benefit over placebo during the bronchiolitis illness or 6
      months post hospitalization. Azithromycin should not be used routinely to treat
      infants hospitalized with bronchiolitis. CLINICAL TRIAL REGISTRATION: The trial
      was registered with the Australian and New Zealand Clinical Trials Register:
      Clinical trials number: ACTRN1261000036099.

PMID- 25954739
TI  - Prospects of risk-sharing agreements for innovative therapies in a context of
      deficit spending in bulgaria.

PMID- 25954738
TI  - Challenges posed by tick-borne rickettsiae: eco-epidemiology and public health
      implications.
AB  - Rickettsiae are obligately intracellular bacteria that are transmitted to
      vertebrates by a variety of arthropod vectors, primarily by fleas and ticks. Once
      transmitted or experimentally inoculated into susceptible mammals, some
      rickettsiae may cause febrile illness of different morbidity and mortality, and
      which can manifest with different types of exhanthems in humans. However, most
      rickettsiae circulate in diverse sylvatic or peridomestic reservoirs without
      having obvious impacts on their vertebrate hosts or affecting humans. We have
      analyzed the key features of tick-borne maintenance of rickettsiae, which may
      provide a deeper basis for understanding those complex invertebrate interactions
      and strategies that have permitted survival and circulation of divergent
      rickettsiae in nature. Rickettsiae are found in association with a wide range of
      hard and soft ticks, which feed on very different species of large and small
      animals. Maintenance of rickettsiae in these vector systems is driven by both
      vertical and horizontal transmission strategies, but some species of Rickettsia
      are also known to cause detrimental effects on their arthropod vectors. Contrary
      to common belief, the role of vertebrate animal hosts in maintenance of
      rickettsiae is very incompletely understood. Some clearly play only the essential
      role of providing a blood meal to the tick while other hosts may supply crucial
      supplemental functions for effective agent transmission by the vectors. This
      review summarizes the importance of some recent findings with known and new
      vectors that afford an improved understanding of the eco-epidemiology of
      rickettsiae; the public health implications of that information for rickettsial
      diseases are also described. Special attention is paid to the co-circulation of
      different species and genotypes of rickettsiae within the same endemic areas and
      how these observations may influence, correctly or incorrectly, trends, and
      conclusions drawn from the surveillance of rickettsial diseases in humans. 

PMID- 25954740
TI  - Growing Burden of Non-Communicable Diseases in the Emerging Health Markets: The
      Case of BRICS.

PMID- 25954741
TI  - DNA oxidation profiles of copper phenanthrene chemical nucleases.
AB  - The deleterious effects of metal-catalyzed reactive oxygen species (ROS) in
      biological systems can be seen in a wide variety of pathological conditions
      including cancer, cardiovascular disease, aging, and neurodegenerative disorder.
      On the other hand however, targeted ROS production in the vicinity of nucleic
      acids-as demonstrated by metal-activated bleomycin-has paved the way for ROS
      active chemotherapeutic drug development. Herein we report mechanistic
      investigations into the oxidative nuclease activity and redox properties of
      copper(II) developmental therapeutics [Cu(DPQ)(phen)](2+) (Cu-DPQ-Phen),
      [Cu(DPPZ)(phen)](2+) (Cu-DPPZ-Phen), and [{Cu(phen)2}2(MU-terph)](terph) (Cu
      Terph), with results being compared directly to Sigman's reagent [Cu(phen)2](2+)
      throughout (phen = 1,10-phenanthroline; DPQ = dipyridoquinoxaline; DPPZ =
      dipyridophenazine; Terph = terephthalate). Oxidative DNA damage was identified at
      the minor groove through use of surface bound recognition elements of methyl
      green, netropsin, and [Co(NH3)6]Cl3 that functioned to control complex
      accessibility at selected regions. ROS-specific scavengers and stabilizers were
      employed to identify the cleavage process, the results of which infer hydrogen
      peroxide produced metal-hydroxo or free hydroxyl radicals ((*)OH) as the
      predominant species. The extent of DNA damage owing to these radicals was then
      quantified through 8-oxo-2'-deoxyguanosine (8-oxo-dG) lesion detection under
      ELISA protocol with the overall trend following Cu-DPQ-Phen > Cu-Terph > Cu-Phen
      > Cu-DPPZ. Finally, the effects of oxidative damage on DNA replication processes
      were investigated using the polymerase chain reaction (PCR) where amplification
      of 120 base pair DNA sequences of varying base content were inhibited
      particularly along A-T rich chains-through oxidative damage of template strands. 

PMID- 25954742
TI  - Remaining challenges in cellular flavin cofactor homeostasis and flavoprotein
      biogenesis.
AB  - The primary role of the water-soluble vitamin B2 (riboflavin) in cell biology is
      connected with its conversion into FMN and FAD, the cofactors of a large number
      of dehydrogenases, oxidases and reductases involved in a broad spectrum of
      biological activities, among which energetic metabolism and chromatin remodeling.
      Subcellular localisation of FAD synthase (EC 2.7.7.2, FADS), the second enzyme in
      the FAD forming pathway, is addressed here in HepG2 cells by confocal microscopy,
      in the frame of its relationships with kinetics of FAD synthesis and delivery to
      client apo-flavoproteins. FAD synthesis catalyzed by recombinant isoform 2 of
      FADS occurs via an ordered bi-bi mechanism in which ATP binds prior to FMN, and
      pyrophosphate is released before FAD. Spectrophotometric continuous assays of the
      reconstitution rate of apo-D-aminoacid oxidase with its cofactor, allowed us to
      propose that besides its FAD synthesizing activity, hFADS is able to operate as a
      FAD "chaperone." The physical interaction between FAD forming enzyme and its
      clients was further confirmed by dot blot and immunoprecipitation experiments
      carried out testing as a client either a nuclear lysine-specific demethylase 1
      (LSD1) or a mitochondrial dimethylglycine dehydrogenase (Me2GlyDH, EC 1.5.8.4).
      Both enzymes carry out similar reactions of oxidative demethylation, in which
      tetrahydrofolate is converted into 5,10-methylene-tetrahydrofolate. A direct
      transfer of the cofactor from hFADS2 to apo-dimethyl glycine dehydrogenase was
      also demonstrated. Thus, FAD synthesis and delivery to these enzymes are crucial
      processes for bioenergetics and nutri-epigenetics of liver cells. 

PMID- 25954743
TI  - Tumor Selectivity of Oncolytic Parvoviruses: From in vitro and Animal Models to
      Cancer Patients.
AB  - Oncolytic virotherapy of cancer is among the innovative modalities being under
      development and especially promising for targeting tumors, which are resistant to
      conventional treatments. Presently, at least a dozen of viruses, belonging to
      nine different virus families, are being tested within the frames of various
      clinical studies in cancer patients. Continuously growing preclinical evidence
      showing that the autonomous rat parvovirus H-1 (H-1PV) is able to kill tumor
      cells that resist conventional treatments and to achieve a complete cure of
      various human tumors in animal models argues for its inclusion in the arsenal of
      oncolytic viruses with an especially promising bench to bedside translation
      potential. Oncolytic parvovirus safe administration to humans relies on the
      intrinsic preference of these agents for quickly proliferating, metabolically,
      and biochemically disturbed tumor versus normal cells (tumor selectivity or
      oncotropism). The present review summarizes and discusses (i) preclinical
      evidence of H-1PV innocuousness for normal cells and healthy tissues in vitro and
      in animals, respectively, (ii) toxicological assessments of H-1PV mono- or
      combined therapy in tumor-bearing virus-permissive animal models, as well as
      (iii) historical results of experimental infection of human cancer patients with
      H-1PV. Altogether, these data argue against a risk of H-1PV inducing significant
      toxic effects in human patients. This highly favorable safety profile allowed the
      translation of H-1PV preclinical research into a Phase I/IIa clinical trial being
      currently in progress. 

PMID- 25954744
TI  - Lung recruitment can improve oxygenation in patients ventilated in continuous
      positive airway pressure/pressure support mode.
AB  - BACKGROUND: Recruitment maneuvers are often used in critical care patients with
      hypoxemic respiratory failure. Although continuous positive airway
      pressure/pressure support (CPAP/PS) ventilation is a frequently used approach,
      but whether lung recruitment also improves oxygenation in spontaneously breathing
      patients has not been investigated yet. The primary objective was to analyze the
      effect of recruitment maneuver on oxygenation in patients ventilated in CPAP/PS
      mode. METHODS: Following baseline measurements PEEP was increased by 5 cmH2O.
      Recruitment maneuver was applied for 40 s with 40 cmH2O of PS. Measurements of
      the difference in PaO2/FiO2 and airway parameters measured by the ventilator were
      recorded immediately after recruitment then 15 and 30 min later. Thirty patients
      ventilated in CPAP/PS mode with a PEEP >=5 cmH2O were enrolled in this
      prospective, observational study if their PaO2/FiO2 ratio was <300 mmHg or
      required an FiO2 >0.5. RESULTS: Following recruitment maneuver patients were
      considered as non-responders (NR, n = 15) if difference of PaO2/FiO2 <20% and
      responders (R, n = 15) if difference of PaO2/FiO2 >=20%. In the NR-group,
      PaO2/FiO2 decreased non-significantly from baseline: median [interquartile],
      PaO2/FiO2 = 176 [120-186] vs. after recruitment: 169 [121-182] mmHg, P = 0.307
      while in the R-group there was significant improvement: 139 [117-164] vs. 230
      [211-323] mmHg, P = 0.01. At the same time points, dead space to tidal volume
      ratio (Vds/Vte) significantly increased in the NR-group Vds/Vte = 32 [27-37] vs.
      36 [25-42]%, P = 0.013 but no significant change was observed in the R-group: 26
      [22-34] vs. 27 [24-33]%, P = 0.386. CONCLUSION: Recruitment maneuver improved
      PaO2/FiO2 ratio by >=20% in 50% of patients ventilated in CPAP/PS mode.

PMID- 25954745
TI  - Two-stage nerve graft using a silicone tube.

PMID- 25954746
TI  - B7-H4 expression is associated with tumor progression and prognosis in patients
      with osteosarcoma.
AB  - Increasing evidences have demonstrated that B7-H4 is associated with tumor
      development and prognosis. However, the clinical significance of B7-H4 expression
      in human osteosarcoma (OS) remains unclear. The aim of present study was to
      examine the B7-H4 expression and to explore its contribution in OS. B7-H4
      expression in OS tissues was examined by immunohistochemistry. Soluble B7-H4 (sB7
      H4) levels in blood were examined by ELISA. The association of B7-H4 expression
      with clinicopathological factors or prognosis was statistically analyzed. Our
      findings demonstrated that B7-H4 expression in OS tissues was significantly
      higher than those in paired normal bone tissues (P < 0.001). sB7-H4 level in OS
      serum samples was significantly higher than that in healthy controls (P = 0.005).
      High B7-H4 expression in tissues and sB7-H4 level were both correlated with
      advanced tumor stage (P < 0.001, P = 0.017, resp.) and distant metastasis (P =
      0.034, P = 0.021, resp.). Additionally, high B7-H4 expression or serum sB7-H4
      levels were significantly related to poor overall survival (P = 0.028, P = 0.005,
      resp.). B7-H4 in tissues and serum samples were an independent factor for
      affecting the survival time of OS patients (P = 0.004, P = 0.041, resp.).
      Collectively, our data suggest that the evaluation of B7-H4 expression in tissues
      and blood is a useful tool for predicting the progression of osteosarcoma and
      prognosis. 

PMID- 25954748
TI  - A gas chromatography-mass spectrometry based study on urine metabolomics in rats
      chronically poisoned with hydrogen sulfide.
AB  - Gas chromatography-mass spectrometry (GS-MS) in combination with multivariate
      statistical analysis was applied to explore the metabolic variability in urine of
      chronically hydrogen sulfide- (H2S-) poisoned rats relative to control ones. The
      changes in endogenous metabolites were studied by partial least squares
      discriminate analysis (PLS-DA) and independent-samples t-test. The metabolic
      patterns of H2S-poisoned group are separated from the control, suggesting that
      the metabolic profiles of H2S-poisoned rats were markedly different from the
      controls. Moreover, compared to the control group, the level of alanine, d
      ribose, tetradecanoic acid, L-aspartic acid, pentanedioic acid, cholesterol,
      acetate, and oleic acid in rat urine of the poisoning group decreased, while the
      level of glycine, d-mannose, arabinofuranose, and propanoic acid increased. These
      metabolites are related to amino acid metabolism as well as energy and lipid
      metabolism in vivo. Studying metabolomics using GC-MS allows for a comprehensive
      overview of the metabolism of the living body. This technique can be employed to
      decipher the mechanism of chronic H2S poisoning, thus promoting the use of
      metabolomics in clinical toxicology. 

PMID- 25954747
TI  - Computer-simulated biopsy marking system for endoscopic surveillance of gastric
      lesions: a pilot study.
AB  - Endoscopic tattoo with India ink injection for surveillance of premalignant
      gastric lesions is technically cumbersome and may not be durable. The aim of the
      study is to evaluate the accuracy of a novel, computer-simulated biopsy marking
      system (CSBMS) developed for the endoscopic marking of gastric lesions. Twenty
      five patients with history of gastric intestinal metaplasia received both CSBMS
      guided marking and India ink injection in five points in the stomach at index
      endoscopy. A second endoscopy was performed at three months. Primary outcome was
      accuracy of CSBMS (distance between CSBMS probe-guided site and tattoo site
      measured by CSBMS). The mean accuracy of CSBMS at angularis was 5.3 +/- 2.2 mm,
      antral lesser curvature 5.7 +/- 1.4 mm, antral greater curvature 6.1 +/- 1.1 mm,
      antral anterior wall 6.9 +/- 1.6 mm, and antral posterior wall 6.9 +/- 1.6 mm.
      CSBMS (2.3 +/- 0.9 versus 12.5 +/- 4.6 seconds; P = 0.02) required less procedure
      time compared to endoscopic tattooing. No adverse events were encountered. CSBMS
      accurately identified previously marked gastric sites by endoscopic tattooing
      within 1 cm on follow-up endoscopy.

PMID- 25954749
TI  - Cardioprotective Activity of Pongamia pinnata in Streptozotocin-Nicotinamide
      Induced Diabetic Rats.
AB  - Pongamia pinnata (L.) Pierre has been used in traditional medicine for the
      treatment for diabetes and metabolic disorder. The aim of this study was to
      investigate the effect of petroleum ether extract of the stem bark of P. pinnata
      (known as PPSB-PEE) on cardiomyopathy in diabetic rats. Diabetes was induced in
      overnight fasted Sprague-Dawley rats by using injection of streptozotocin (55
      mg/kg, i.p.). Nicotinamide (100 mg/kg, i.p.) was administered 20 min before
      administration of streptozotocin. Rats were divided into group I: nondiabetic,
      group II: diabetic control (tween 80, 2%; 10 mL/kg, p.o.) as vehicle, and group
      III: PPSB-PEE (100 mg/kg, p.o.). The blood glucose level, ECG, hemodynamic
      parameters, cardiotoxic and antioxidant biomarkers, and histology of heart were
      carried out after 4 months after STZ with nicotinamide injection. PPSB-PEE
      treatment improved the electrocardiographic, hemodynamic changes; LV contractile
      function; biological markers; oxidative stress parameters; and histological
      changes in STZ induced diabetic rats. PPSB-PEE (100 mg/kg, p.o.) decreased blood
      glucose level, improved electrocardiographic parameters (QRS, QT, and QTc
      intervals) and hemodynamic parameters (SBP, DBP, EDP, max dP/dt, contractility
      index, and heart rate), controlled levels of cardiac biomarkers (CK-MB, LDH, and
      AST), and improved oxidative stress (SOD, MDA, and GSH) in diabetic rats. PPSB
      PEE is a promising remedy against cardiomyopathy in diabetic rats.

PMID- 25954750
TI  - A novel animal model of impaired glucose tolerance induced by the interaction of
      vitamin E deficiency and (60)Co radiation.
AB  - Impaired glucose tolerance (IGT), known as the prediabetes stage, is usually
      induced by habits of life or environmental factors. Established IGT animal models
      are mostly conducted with chemical compounds such as streptozocin or genetic
      modification. However, the occasion of exposure to these factors in daily life is
      seldom. The objective of this study was to establish a new animal model of IGT
      induced by VE deficiency in diet and exposure to radiation. SD rats were treated
      individually or in combination of these two factors. In the combination group,
      the calculated insulin sensitivity index decreased; then HOMA-beta value
      increased. Oxidative damage and IGT were observed. Insulin secretion level in
      perfusate from pancreas response to glucose was characterized by a rapid but
      reduced first phase and an obviously defective second phase upon pancreas
      perfusion. Histopathological images demonstrated the pathological changes.
      Western blotting analysis showed that the insulin signaling pathway was
      downregulated. The interaction of VE deficiency in diet and exposure to radiation
      could break the equilibrium of oxidation and antioxidation and result in IGT.
      More importantly, a new IGT model was successfully established which may be
      conducive to further research into development of drugs against human IGT. 

PMID- 25954751
TI  - SR and LR Union Suture for the Treatment of Myopic Strabismus Fixus: Is Scleral
      Fixation Necessary?
AB  - PURPOSE: To evaluate and compare the effectiveness of scleral fixation SR and LR
      union suture and nonscleral fixation union suture for the treatment of myopic
      strabismus fixus. METHODS: Retrospective review of 32 eyes of 22 patients with
      myopic strabismus fixus who had undergone union suture of superior rectus (SR)
      and lateral rectus (LR) with or without scleral fixation, and follow-up longer
      than 6 months at Hong Kong Eye Hospital from 2006 to 2013. Surgical techniques
      and outcomes in terms of ocular alignment are analyzed. RESULTS: There is
      significant overall improvement both in postoperative angle of esodeviation (P <
      0.01) and postoperative range of movement (P = 0.042). Comparing between the
      sclera fixation group (11 eyes) versus nonscleral fixation group (21 eyes), the
      postoperative horizontal deviation, the postoperative vertical deviation,
      successful outcome, and the change in horizontal deviation were not significantly
      different (P > 0.05). CONCLUSIONS: Union suture of SR and LR is an effective
      procedure in correcting myopic strabismus fixus. Fixation of the union suture to
      the sclera does not improve surgical outcome.

PMID- 25954752
TI  - An Integrated Modeling and Experimental Approach to Study the Influence of
      Environmental Nutrients on Biofilm Formation of Pseudomonas aeruginosa.
AB  - The availability of nutrient components in the environment was identified as a
      critical regulator of virulence and biofilm formation in Pseudomonas aeruginosa.
      This work proposes the first systems-biology approach to quantify microbial
      biofilm formation upon the change of nutrient availability in the environment.
      Specifically, the change of fluxes of metabolic reactions that were positively
      associated with P. aeruginosa biofilm formation was used to monitor the trend for
      P. aeruginosa to form a biofilm. The uptake rates of nutrient components were
      changed according to the change of the nutrient availability. We found that
      adding each of the eleven amino acids (Arg, Tyr, Phe, His, Iso, Orn, Pro, Glu,
      Leu, Val, and Asp) to minimal medium promoted P. aeruginosa biofilm formation.
      Both modeling and experimental approaches were further developed to quantify P.
      aeruginosa biofilm formation for four different availability levels for each of
      the three ions that include ferrous ions, sulfate, and phosphate. The developed
      modeling approach correctly predicted the amount of biofilm formation. By
      comparing reaction flux change upon the change of nutrient concentrations,
      metabolic reactions used by P. aeruginosa to regulate its biofilm formation are
      mainly involved in arginine metabolism, glutamate production, magnesium
      transport, acetate metabolism, and the TCA cycle. 

PMID- 25954753
TI  - Prevalence of Active Trachoma and Its Associated Factors among Rural and Urban
      Children in Dera Woreda, Northwest Ethiopia: A Comparative Cross-Sectional Study.
AB  - BACKGROUND: Trachoma is the most common infectious cause of blindness worldwide.
      Once an epidemic in most parts of the world, it has largely now disappeared from
      developed countries. However, it continues to be endemic in many developing
      countries like Ethiopia. Even if several studies were conducted in different
      parts of Ethiopia, most of them did not show the independent predictors for rural
      and urban children separately. Therefore, this study aimed at assessing the
      prevalence and associated factors of active trachoma in urban and rural children.
      METHODS: Community based comparative cross-sectional study was conducted in Dera
      woreda. Multistage sampling technique was used to select 671 children of one up
      to nine years of age. Data were collected by face to face interview and
      observation using a structured and pretested questionnaire. Binary Logistic
      Regression Model was fitted to consider adding independent predictors of outcome.
      RESULTS: Out of 671 children, 20 (9.3%) of urban and 85 (18.6%) of rural children
      were positive for active trachoma. Having discharge on eye (AOR = 6.9, 95% CI:
      1.79-27.89), presence of liquid waste around the main house (AOR = 5.6, 95% CI:
      1.94-16.18), and living in households without latrine (AOR = 4.39, 95% CI: 1.39
      13.89) were significantly associated with active trachoma of urban children.
      Rural children who had discharge on their eye (AOR = 5.86, 95% CI: 2.78-12.33),
      those who had unclean face (AOR = 4.68, 95% CI: 2.24-9.81), and those living in
      households with feces around their main houses (AOR = 1.94, 95% CI: 1.04-3.62)
      were significantly associated with active trachoma. CONCLUSION: The result showed
      that the prevalence of active trachoma in urban areas of the district was below
      WHO threshold of 10% to determine trachoma as public health problem. However, in
      rural areas of the district it is far from elimination of trachoma as a public
      health problem. Thus, in order to improve awareness of the community there is a
      need of health education programs regarding facial cleanliness, utilization of
      latrine, and proper solid waste and liquid waste disposal using multidisciplinary
      approach.

PMID- 25954754
TI  - Membrane transport: ionic environments, signal transduction, and development of
      therapeutic targets.

PMID- 25954755
TI  - Chitosan Prevents Gentamicin-Induced Nephrotoxicity via a Carbonyl Stress
      Dependent Pathway.
AB  - Aminoglycosides are widely used to treat infections; however, their applications
      are limited by nephrotoxicity. With the increase of antibiotic resistance, the
      use of aminoglycosides is inevitable. Low-molecular-weight chitosan (LMWC) has
      shown renal protective effects in dialysis patients. However, no study has
      evaluated LMWC for preventing aminoglycoside-induced nephrotoxicity or determined
      the mechanisms underlying the renal protective effects. In this study, LMWC (165
      or 825 mg/kg/day) or metformin (100 mg/kg/day) was orally administered for 13
      days to rats with nephropathy induced by gentamicin (GM), a kind of
      aminoglycoside (150 mg/kg/day i.p. for 6 days). Both LMCW doses improved renal
      function. Serum creatinine levels improved in rats treated with 165 and 825
      mg/kg/day LMWC (from 2.14 +/- 0.74 mg/dL to 1.26 +/- 0.46 mg/dL and 0.69 +/- 0.12
      mg/dL, resp., P < 0.05). Blood urea nitrogen levels were also improved in these
      rats (from 73.73 +/- 21.13 mg/dL to 58.70 +/- 22.71 mg/dL and 28.82 +/- 3.84
      mg/dL, resp., P < 0.05). Additionally, renal tissue morphology improved after
      LMWC treatment, and accumulation of renal methylglyoxal, a damage factor
      associated with carbonyl stress, was reversed. These results show that LMWC
      prevents GM-induced renal toxicity via a carbonyl stress-dependent pathway.

PMID- 25954756
TI  - Introduction of auricular acupuncture in elderly patients suffering from major
      depression: protocol of a mixed methods feasibility study.
AB  - BACKGROUND: Due to an increasing number of elderly people suffering from major
      depression and potential side effects of the prescribed drugs, the introduction
      of new therapeutic approaches is needed. Currently, in Germany, auricular
      acupuncture is no part of clinical care for gerontopsychiatric patients. Based on
      promising clinical experiences and existing evidence for treating addiction and
      trauma, a benefit of auricular acupuncture integrated in existing treatment
      programs in elderly patients may be hypothesized. Within this project auricular
      acupuncture according to the National Acupuncture Detoxification Association
      (NADA) will be integrated in the multimodal treatment regime for elderly patients
      with major depression in a daytime ward setting. METHODS/DESIGN: To evaluate the
      feasibility and acceptance a mixed method approach is used. In a day clinic, a
      sample of 20 psychogeriatric patients with the diagnosis of major depression will
      be enrolled. The patients will receive a total of nine auricular acupuncture
      treatments according to the standardized NADA protocol in a group setting. The
      therapeutic process, its organization, the experience, and the willingness of
      patients to participate will be evaluated by interviews with patients and the
      therapeutic team. Data will be analyzed qualitatively using content analysis.
      Additionally, quantitative outcome parameters will be measured by standardized
      questionnaires.

PMID- 25954757
TI  - Head-neck taper corrosion in hip arthroplasty.
AB  - Modularity at the head-neck junction of the femoral component in THA became
      popular as a design feature with advantages of decreasing implant inventory and
      allowing adjustment of leg length, offset, and soft tissue balancing through
      different head options. The introduction of a new modular interface to femoral
      stems that were previously monoblock, or nonmodular, comes with the potential for
      corrosion at the taper junction through mechanically assisted crevice corrosion.
      The incidence of revision hip arthroplasty is on the rise and along with improved
      wear properties of polyethylene and ceramic, use of larger femoral head sizes is
      becoming increasingly popular. Taper corrosion appears to be related to all of
      its geometric parameters, material combinations, and femoral head size. This
      review article discusses the pathogenesis, risk factors, clinical assessment, and
      management of taper corrosion at the head-neck junction. 

PMID- 25954758
TI  - Biomechanical Stability of Dental Implants in Augmented Maxillary Sites: Results
      of a Randomized Clinical Study with Four Different Biomaterials and PRF and a
      Biological View on Guided Bone Regeneration.
AB  - INTRODUCTION: Bone regenerates mainly by periosteal and endosteal humoral and
      cellular activity, which is given only little concern in surgical techniques and
      choice of bone grafts for guided bone regeneration. This study investigates on a
      clinical level the biomechanical stability of augmented sites in maxillary bone
      when a new class of moldable, self-hardening calcium-phosphate biomaterials (SHB)
      is used with and without the addition of Platelet Rich Fibrin (aPRF) in the
      Piezotome-enhanced subperiosteal tunnel-technique (PeSPTT). MATERIAL AND METHODS:
      82 patients with horizontal atrophy of anterior maxillary crest were treated with
      PeSPTT and randomly assigned biphasic (60% HA/40% bTCP) or monophasic (100% bTCP)
      SHB without or with addition of aPRF. 109 implants were inserted into the
      augmented sites after 8.3 months and the insertion-torque-value (ITV) measured as
      clinical expression of the (bio)mechanical stability of the augmented bone and
      compared to ITVs of a prior study in sinus lifting. RESULTS: Significant better
      results of (bio)mechanical stability almost by two-fold, expressed by higher ITVs
      compared to native bone, were achieved with the used biomaterials and more
      constant results with the addition of aPRF. CONCLUSION: The use of SHB alone or
      combined with aPRF seems to be favourable to achieve a superior (bio)mechanical
      stable restored alveolar bone.

PMID- 25954759
TI  - Differential Effects of Endotracheal Suctioning on Gas Exchanges in Patients with
      Acute Respiratory Failure under Pressure-Controlled and Volume-Controlled
      Ventilation.
AB  - This study was conducted to evaluate the effects of open endotracheal suctioning
      on gas exchange and respiratory mechanics in ARF patients under the modes of PCV
      or VCV. Ninety-six ARF patients were treated with open endotracheal suctioning
      and their variations in respiratory mechanics and gas exchange after the suctions
      were compared. Under PCV mode, compared with the initial level of tidal volume (V
      T ), ARF patients showed 30.0% and 27.8% decrease at 1 min and 10 min,
      respectively. Furthermore, the initial respiratory system compliance (C rs)
      decreased by 29.6% and 28.5% at 1 min and 10 min, respectively. Under VCV mode,
      compared with the initial level, 38.6% and 37.5% increase in peak airway pressure
      (PAP) were found at 1 min and 10 min, respectively. Under PCV mode, the initial
      PaO2 increased by 6.4% and 10.2% at 3 min and 10 min, respectively, while 18.9%
      and 30.6% increase of the initial PaO2 were observed under VCV mode. Summarily,
      endotracheal suctioning may impair gas exchange and decrease lung compliance in
      ARF patients receiving mechanical ventilation under both PCV and VCV modes, but
      endotracheal suctioning effects on gas exchange were more severe and longer
      lasting under PCV mode than VCV.

PMID- 25954760
TI  - Intuitive web-based experimental design for high-throughput biomedical data.
AB  - Big data bioinformatics aims at drawing biological conclusions from huge and
      complex biological datasets. Added value from the analysis of big data, however,
      is only possible if the data is accompanied by accurate metadata annotation.
      Particularly in high-throughput experiments intelligent approaches are needed to
      keep track of the experimental design, including the conditions that are studied
      as well as information that might be interesting for failure analysis or further
      experiments in the future. In addition to the management of this information,
      means for an integrated design and interfaces for structured data annotation are
      urgently needed by researchers. Here, we propose a factor-based experimental
      design approach that enables scientists to easily create large-scale experiments
      with the help of a web-based system. We present a novel implementation of a web
      based interface allowing the collection of arbitrary metadata. To exchange and
      edit information we provide a spreadsheet-based, humanly readable format.
      Subsequently, sample sheets with identifiers and metainformation for data
      generation facilities can be created. Data files created after measurement of the
      samples can be uploaded to a datastore, where they are automatically linked to
      the previously created experimental design model. 

PMID- 25954761
TI  - Ocular rigidity and outflow facility in nonproliferative diabetic retinopathy.
AB  - PURPOSE: To compare ocular rigidity (OR) and outflow facility (C) in patients
      with nonproliferative diabetic retinopathy (NPDR) and control subjects. METHODS:
      Twenty-four patients with NPDR (NPDR group) and 24 controls (control group)
      undergoing cataract surgery were enrolled. NPDR group was further divided into
      patients with mild NPDR (NPDR1-group) and patients with moderate and/or severe
      NPDR (NPDR2-group). After cannulation of the anterior chamber, a computer
      controlled device was used to infuse saline and increase the intraocular pressure
      (IOP) in a stepping procedure from 15 to 40 mmHg. Ocular rigidity and outflow
      facility coefficients were estimated from IOP and volume recordings. RESULTS:
      Ocular rigidity was 0.0205 MUL(-1) in NPDR group and 0.0202 MUL(-1) in control
      group (P = 0.942). In NPDR1-group, OR was 0.017 MUL(-1) and in NPDR2-group it was
      0.025 MUL(-1) (P = 0.192). Outflow facility was 0.120 MUL/min/mmHg in NPDR-group
      compared to 0.153 MUL/min/mmHg in the control group at an IOP of 35 mmHg (P =
      0.151). There was no difference in C between NPDR1-group and NPDR2-group (P =
      0.709). CONCLUSIONS: No statistically significant differences in ocular rigidity
      and outflow facility could be documented between diabetic patients and controls.
      No difference in OR and C was detected between mild NPDR and severe NPDR.

PMID- 25954762
TI  - Is type 2 diabetes really resolved after laparoscopic sleeve gastrectomy? Glucose
      variability studied by continuous glucose monitoring.
AB  - The study was carried out on type 2 diabetic obese patients who underwent
      laparoscopic sleeve gastrectomy (LSG). Patients underwent regular glycemic
      controls throughout 3 years and all patients were defined cured from diabetes
      according to conventional criteria defined as normalization of fasting glucose
      levels and glycated hemoglobin in absence of antidiabetic therapy. After 3 years
      of follow-up, Continuous Glucose Monitoring (CGM) was performed in each patient
      to better clarify the remission of diabetes. In this study, we found that the
      diabetes resolution after LSG occurred in 40% of patients; in the other 60%, even
      if they showed a normal fasting glycemia and A1c, patients spent a lot of time in
      hyperglycemia. During the oral glucose tolerance test (OGTT), we found that 2 h
      postload glucose determinations revealed overt diabetes only in a small group of
      patients and might be insufficient to exclude the diagnosis of diabetes in the
      other patients who spent a lot of time in hyperglycemia, even if they showed a
      normal glycemia (<140 mg/dL) at 120 minutes OGTT. These interesting data could
      help clinicians to better individualize patients in which diabetes is not
      resolved and who could need more attention in order to prevent chronic
      complications of diabetes.

PMID- 25954764
TI  - Increased NY-ESO-1 expression and reduced infiltrating CD3+ T cells in cutaneous
      melanoma.
AB  - NY-ESO-1 is a cancer-testis antigen aberrantly expressed in melanomas, which may
      serve as a robust and specific target in immunotherapy. NY-ESO-1 antigen
      expression, tumor features, and the immune profile of tumor infiltrating
      lymphocytes were assessed in primary cutaneous melanoma. NY-ESO-1 protein was
      detected in 20% of invasive melanomas (16/79), rarely in in situ melanoma (1/10)
      and not in benign nevi (0/20). Marked intratumoral heterogeneity of NY-ESO-1
      protein expression was observed. NY-ESO-1 expression was associated with
      increased primary tumor thickness (P = 0.007) and inversely correlated with
      superficial spreading melanoma (P < 0.02). NY-ESO-1 expression was also
      associated with reduced numbers and density of CD3+ tumor infiltrating
      lymphocytes (P = 0.017). When NY-ESO-1 protein was expressed, CD3+ T cells were
      less diffusely infiltrating the tumor and were more often arranged in small
      clusters (P = 0.010) or as isolated cells (P = 0.002) than in large clusters of
      more than five lymphocytes. No correlation of NY-ESO-1 expression with gender,
      age, tumor site, ulceration, lymph node sentinel status, or survival was
      observed. NY-ESO-1 expression in melanoma was associated with tumor progression,
      including increased tumor thickness, and with reduced tumor infiltrating
      lymphocytes. 

PMID- 25954765
TI  - Control Over Stress Accelerates Extinction of Drug Seeking Via Prefrontal
      Cortical Activation.
AB  - Extinction is a form of inhibitory learning viewed as an essential process in
      suppressing conditioned responses to drug cues, yet there is little information
      concerning experiential variables that modulate its formation. Coping factors
      play an instrumental role in determining how adverse life events impact the
      transition from casual drug use to addiction. Here we provide evidence in rat
      that prior exposure to controllable stress accelerates the extinction of cocaine
      seeking behavior relative to uncontrollable or no stress exposure. Subsequent
      experimentation using high-speed optogenetic tools determined if the infralimbic
      region (IL) of the ventral medial prefrontal cortex mediates the impact of
      controllable stress on cocaine-seeking behavior. Photoinhibition of pyramidal
      neurons in the IL during coping behavior did not interfere with subject's ability
      to control the stressor, but prevented the later control-induced facilitation of
      extinction. These results provide strong evidence that the degree of behavioral
      control over adverse events, rather than adverse events per se, potently
      modulates the extinction of cocaine-seeking behavior, and that controllable
      stress engages prefrontal circuitry that primes future extinction learning.

PMID- 25954767
TI  - Rescue and emergency management of a man-made disaster: lesson learnt from a
      collapse factory building, Bangladesh.
AB  - A tragic disaster occurred on April 24, 2013, in Bangladesh, when a nine storied
      building in a suburban area collapsed and killed 1115 people and injured many
      more. The study describes the process of rescue operation and emergency
      management services provided in the event. Data were collected using qualitative
      methods including in-depth interviews and a focus group discussion with the
      involved medical students, doctors, volunteers, and local people. Immediately
      after the disaster, rescue teams came to the place from Bangladesh Armed Forces,
      Bangladesh Navy, Bangladesh Air Force, and Dhaka Metropolitan and local Police
      and doctors, medical students, and nurses from nearby medical college hospitals
      and private hospitals and students from colleges and universities including local
      civil people. Doctors and medical students provided 24-hour services at the
      disaster place and in hospitals. Minor injured patients were treated at health
      camps and major injured patients were immediately carried to nearby hospital.
      Despite the limitations of a low resource setting, Bangladesh faced a tremendous
      challenge to manage the man-made disaster and experienced enormous support from
      different sectors of society to manage the disaster carefully and saved thousands
      of lives. This effort could help to develop a standard emergency management
      system applicable to Bangladesh and other counties with similar settings. 

PMID- 25954763
TI  - Progress and challenges toward the development of vaccines against avian
      infectious bronchitis.
AB  - Avian infectious bronchitis (IB) is a widely distributed poultry disease that has
      huge economic impact on poultry industry. The continuous emergence of new IBV
      genotypes and lack of cross protection among different IBV genotypes have been an
      important challenge. Although live attenuated IB vaccines remarkably induce
      potent immune response, the potential risk of reversion to virulence,
      neutralization by the maternal antibodies, and recombination and mutation events
      are important concern on their usage. On the other hand, inactivated vaccines
      induce a weaker immune response and may require multiple dosing and/or the use of
      adjuvants that probably have potential safety risks and increased economic
      burdens. Consequently, alternative IB vaccines are widely sought. Recent advances
      in recombinant DNA technology have resulted in experimental IB vaccines that show
      promise in antibody and T-cells responses, comparable to live attenuated
      vaccines. Recombinant DNA vaccines have also been enhanced to target multiple
      serotypes and their efficacy has been improved using delivery vectors,
      nanoadjuvants, and in ovo vaccination approaches. Although most recombinant IB
      DNA vaccines are yet to be licensed, it is expected that these types of vaccines
      may hold sway as future vaccines for inducing a cross protection against multiple
      IBV serotypes. 

PMID- 25954768
TI  - ACOustic: A Nature-Inspired Exploration Indicator for Ant Colony Optimization.
AB  - A statistical machine learning indicator, ACOustic, is proposed to evaluate the
      exploration behavior in the iterations of ant colony optimization algorithms.
      This idea is inspired by the behavior of some parasites in their mimicry to the
      queens' acoustics of their ant hosts. The parasites' reaction results from their
      ability to indicate the state of penetration. The proposed indicator solves the
      problem of robustness that results from the difference of magnitudes in the
      distance's matrix, especially when combinatorial optimization problems with
      rugged fitness landscape are applied. The performance of the proposed indicator
      is evaluated against the existing indicators in six variants of ant colony
      optimization algorithms. Instances for travelling salesman problem and quadratic
      assignment problem are used in the experimental evaluation. The analytical
      results showed that the proposed indicator is more informative and more robust. 

PMID- 25954769
TI  - On a cubically convergent iterative method for matrix sign.
AB  - We propose an iterative method for finding matrix sign function. It is shown that
      the scheme has global behavior with cubical rate of convergence. Examples are
      included to show the applicability and efficiency of the proposed scheme and its
      reciprocal. 

PMID- 25954770
TI  - Pregnancy Outcome of Multiparous Women Aged over 40 Years.
AB  - Objective. The aim of this study was to evaluate the effect of maternal age on
      prenatal and obstetric outcome in multiparaous women. Materials and Methods. A
      retrospective case control study was conducted, including women aged 40 years and
      over (study group, n = 97) who delivered at 20 week's gestation or beyond and
      women aged 20-29 years (control group, n = 97). Results. The mean age of women in
      the study group was 41.2 +/- 1.7 years versus 25.4 +/- 2.3 years in the control
      group. Advanced maternal age was associated with a significantly higher rate of
      hypertension, diabetes mellitus, fetal complication, and 5-minute Apgar scores <7
      (P < 0.05). Caeserean section rate, incidence of placental abruption, preterm
      delivery, and neonatal intensive care unit admission were more common in the
      older group, but the differences were not statistically significant. Conclusions.
      Advanced maternal age is related to maternal and neonatal complications. 

PMID- 25954772
TI  - Radical aryl migration reactions and synthetic applications.
AB  - Radical aryl migration reactions are of particular interest to the chemical
      community due to their potential application in radical chemistry and organic
      synthesis. The neophyl rearrangements used as radical clocks for examining the
      radical-molecular reactions have been known for decades. The combinations of
      these migrations with other radical reactions have provided a wide range of novel
      synthetic methodologies that are complementary to nucleophilic rearrangements.
      This review will give an overview of various types of radical aryl migrations,
      with an emphasis on their mechanistic studies from a historical point of view, as
      well as their application in tandem radical reactions. 

PMID- 25954771
TI  - Psychiatric assessment and screening for the elderly in primary care: design,
      implementation, and preliminary results.
AB  - INTRODUCTION: We describe the design and implementation of a psychiatric
      collaborative care model in a University-based geriatric primary care practice.
      Initial results of screening for anxiety and depression are reported. METHODS AND
      MATERIALS: Screens for anxiety and depression were administered to practice
      patients. A mental health team, consisting of a psychiatrist, mental health nurse
      practitioner and social worker, identified patients who on review of screening
      and chart data warranted evaluation or treatment. Referrals for mental health
      interventions were directed to members of the mental health team, primary care
      physicians at the practice, or community providers. RESULTS: Subjects (N=1505)
      comprised 38.2% of the 3940 unique patients seen at the practice during the 4
      year study period. 37.1% (N=555) screened positive for depression, 26.9 % (N=405)
      for anxiety, and 322 (21.4%) screened positive for both. Any positive score was
      associated with age (p<0.033), female gender (p<0.006), and a non-significant
      trend toward living alone (p<0.095). 8.87% had suicidal thoughts. CONCLUSIONS:
      Screening captured the most affectively symptomatic patients, including those
      with suicidal ideation, for intervention. The partnering of mental health
      professionals and primary care physicians offers a workable model for addressing
      the scarcity of expertise in geriatric psychiatry.

PMID- 25954773
TI  - The emergence of sulfoxides as efficient ligands in transition metal catalysis.
AB  - Sulfoxides are capable of forming stable complexes with transition metals and
      there have been many comprehensive studies into their binding properties.
      However, the use of sulfoxides, particularly chiral sulfoxides, as ligands in
      transition metal catalysis is rather less well developed. This review aims to
      describe these catalytic studies and covers new developments that are showing
      very promising results and that have led to a renewed interest in this field. 

PMID- 25954774
TI  - Mixed ligand copper(II) dicarboxylate complexes: the role of co-ligand
      hydrophobicity in DNA binding, double-strand DNA cleavage, protein binding and
      cytotoxicity.
AB  - A few water soluble mixed ligand copper(ii) complexes of the type
      [Cu(bimda)(diimine)] , where bimda is N-benzyliminodiacetic acid and diimine is
      2,2'-bipyridine (bpy, ) or 1,10-phenanthroline (phen, ) or 5,6-dimethyl-1,10
      phenanthroline (5,6-dmp, ) or 3,4,7,8-tetramethyl-1,10-phenanthroline (3,4,7,8
      tmp, ) and dipyrido[3,2-d: 2',3'-f]quinoxaline (dpq, ), have been successfully
      isolated and characterized by elemental analysis and other spectral techniques.
      The coordination geometry around copper(ii) in is described as distorted square
      based pyramidal while that in is described as square pyramidal. Absorption
      spectral titrations and competitive DNA binding studies reveal that the intrinsic
      DNA binding affinity of the complexes depends upon the diimine co-ligand, dpq ()
      > 3,4,7,8-tmp () > 5,6-dmp () > phen () > bpy (). The phen and dpq co-ligands are
      involved in the pi-stacking interaction with DNA base pairs while the 3,4,7,8
      tmp/5,6-dmp and bpy co-ligands are involved in respectively hydrophobic and
      surface mode of binding with DNA. The small enhancement in the relative viscosity
      of DNA upon binding to supports the DNA binding modes proposed. Interestingly,
      and are selective in exhibiting a positive induced CD band (ICD) upon binding to
      DNA suggesting that they induce B to A conformational change. In contrast, and
      show CD responses which reveal their involvement in strong DNA binding. The
      complexes are unique in displaying prominent double-strand DNA cleavage while
      effects only single-strand DNA cleavage, and their ability to cleave DNA in the
      absence of an activator varies as > > > > . Also, all the complexes exhibit
      oxidative double-strand DNA cleavage activity in the presence of ascorbic acid,
      which varies as > > > > . The ability of the complexes to bind and cleave the
      protein BSA varies in the order > > > > . Interestingly, and cleave the protein
      non-specifically in the presence of H2O2 as an activator suggesting that they can
      act also as chemical proteases. It is remarkable that exhibit cytotoxicity
      against human breast cancer cell lines (MCF-7) with potency higher than the
      widely used drug cisplatin indicating that they have the potential to act as
      effective anticancer drugs in a time dependent manner. The morphological
      assessment data obtained by using Hoechst 33258 staining reveal that and induce
      apoptosis much more effectively than other complexes. Also, the alkaline single
      cell gel electrophoresis study (comet assay) suggests that the same complexes
      induce DNA fragmentation more efficiently than others. 

PMID- 25954775
TI  - Determination of the local corrosion rate of magnesium alloys using a shear force
      mounted scanning microcapillary method.
AB  - The successful development of scanning probe techniques to characterize corrosion
      in situ using multifunctional probes is intrinsically tied to surface topography
      signal decoupling from the measured electrochemical fluxes. One viable strategy
      is the shear force controlled scanning microcapillary method. Using this method,
      pulled quartz micropipettes with an aperture of 500 nm diameter were used to
      resolve small and large variations in topography in order to quantify the local
      corrosion rate of microgalvanically and galvanically corroded Mg alloys. To
      achieve topography monitoring of corroded surfaces, shear force feedback was
      employed to position the micropipette at a reproducible working height above the
      substrate. We present proof of concept measurements over a galvanic couple of a
      magnesium alloy (AE44) and mild steel along with a microgalvanically corroded
      ZEK100 Mg alloy, which illustrates the ability of shear force to track small (1.4
      MUm) and large (700 MUm) topographic variations from high aspect ratio features.
      Furthermore, we demonstrate the robustness of the technique by acquiring
      topographic data for 4 mm along the magnesium-steel galvanic couple sample and a
      250 * 30 MUm topography map over the ZEK100 Mg alloy. All topography results were
      benchmarked using standard optical microscopies (profilometry and confocal laser
      scanning microscopy). 

PMID- 25954777
TI  - An organic photovoltaic featuring graphene nanoribbons.
AB  - A combination of graphene nanoribbons (GNRs) and carbon nanotubes (CNTs) was
      deployed as a potential candidate to replace the commonly used hole transport
      material poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) ( PEDOT: PSS) in
      a high performance organic photovoltaic. A power conversion efficiency (PCE) of
      7.6% has been obtained using inkjet printing to fabricate the photovoltaic along
      with the presence of C60-bis as an electron transporting material.

PMID- 25954776
TI  - A comparative study on edible Agaricus mushrooms as functional foods.
AB  - Agaricus bisporus is a cultivated mushroom; A. bitorquis, A. campestris and A.
      macrosporus are edible mushrooms growing wild in nature. A chemical
      characterization was carried out with samples that originated in Serbia.
      Antioxidant, antimicrobial and anti-quorum sensing properties of their methanolic
      and ethanolic extracts were assessed. A. campestris had the lowest caloric value
      and total sugar content and showed the highest concentration in organic and
      phenolic acids, as also in tocopherols (mainly gamma-tocopherol). In general, the
      methanolic extracts showed higher antioxidant, but lower antibacterial and
      antifungal potential than ethanolic ones. Sub-inhibitory concentrations of the
      ethanolic extracts demonstrated reduction of virulence factors, AQ inhibition
      zones, twitching and swimming motility. The biofilm forming capability of P.
      aeruginosa PAO1 was also reduced in a concentration-dependent manner at sub-MIC
      values. The extracts of the tested Agaricus species are a promising source of
      antioxidant, antimicrobial and antiquorum sensing compounds.

PMID- 25954778
TI  - Correction.
AB  - In the article by Eicken et al (Eicken A, Schubert S, Hager A, Horer J,
      McElhinney DB, Hess J, Ewert P, Berger F. Percutaneous trcuspid valve
      implantation: two-center experience with midterm results. Circ Cardiovasc Interv.
      2015;8:e002155. DOI: 10.1161/CIRCINTERVENTIONS.114.002155.), which published
      online April 14, 2015, and appears in the April 2015 issue of the journal, a
      correction was needed. On page 1, in the affiliations footnote, "Klinik fur Herz
      und Gefaschirurgie (S.S., F.B.), Deutsches Herzzentrum Munchen, Technische
      Universitat Munchen, Munich, Germany; Klinik fur Kinderkardiologie und angeborene
      Herzfehler, Deutsches Herzzentrum Berlin, Berlin, Germany (J. Horer)," has been
      changed to read, "Klinik fur Herz-und Gefaschirurgie (J. Horer), Deutsches
      Herzzentrum Munchen, Munich, Germany; Klinik fur Kinderkardiologie und angeborene
      Herzfehler, Deutsches Herzzentrum Berlin, Berlin, Germany (S.S., F.B.)." The
      authors regret the error. This correction has been made to the online version of
      the article, which is available at http://
      circinterventions.ahajournals.org/content/8/4/e002155.

PMID- 25954779
TI  - The "continuum of pain" and the American Academy of Pain Medicine.

PMID- 25954780
TI  - Author response.

PMID- 25954781
TI  - The spirit of nursing.

PMID- 25954782
TI  - Preventing skin damage.

PMID- 25954783
TI  - Ependymal cells in cerebrospinal fluid: a traumatic occurrence.

PMID- 25954784
TI  - Goodbye Tadd.

PMID- 25954785
TI  - Dangling dollars.

PMID- 25954787
TI  - Informed screening.

PMID- 25954786
TI  - New era of health care spending could roll into the good times.

PMID- 25954789
TI  - Compare before deciding. Cytotoxic drugs for relapsed or refractory multiple
      myeloma.

PMID- 25954788
TI  - Pomalidomide. A last-line treatment option for multiple myeloma.
AB  - Treatment options for multiple myeloma dwindle with each relapse. There is no
      standard treatment for patients who relapse. Pomalidomide, an analogue of
      thalidomide and lenalidomide, has been authorised in the EU for the treatment of
      relapsed and refractory multiple myeloma after at least two previous lines of
      treatment including lenalidomide and bortezomib. Clinical evaluation of
      pomalidomide in this setting is based on an unblinded controlled trial in 455
      patients who had already received several treatments, including lenalidomide.
      Nearly one-third of the patients were refractory to thalidomide.The patients were
      assigned to either high-dose dexamethasone or pomalidomide + low-dose
      dexamethasone. Pomalidomide prolonged median survival by at least 3 months. It
      has not been compared to thalidomide. The known adverse effects of pomalidomide
      include peripheral neuropathy, venous thrombosis, cutaneous disorders and
      neutropenia. Few cardiac disorders have been reported. Some drug-drug
      interactions can result in pomalidomide overdose. Pomalidomide is teratogenic. In
      practice, despite its adverse effects, third-line treatment with pomalidomide is
      an option for some patients who want to prolong survival by a few weeks: when
      myeloma is refractory to lenalidomide and thalidomide and their adverse effects
      were acceptable.

PMID- 25954790
TI  - Common stem -antrone.

PMID- 25954791
TI  - Artesunate. The standard intravenous treatment for severe attacks of malaria.
AB  - Intravenous artesunate is more effective in reducing mortality than injectable
      quinine. It also has a better adverse effect profile and is more convenient to
      use.

PMID- 25954792
TI  - Compare before deciding. Treatment of HIV infection.

PMID- 25954793
TI  - Telithromycin: review of adverse effects.
AB  - Telithromycin is a macrolide antibiotic that has been marketed since the early
      2000s. It has not been shown to be more effective against any bacteria than other
      macrolide antibiotics. Its antibacterial activity is in no way remarkable. In
      early 2014, we reviewed its adverse effect profile using data from periodic
      safety update reports, drug regulatory agencies, and detailed published case
      reports. In addition to the adverse effect profile telithromycin shares with the
      other macrolides, it provokes several specific adverse effects: visual
      disturbances due to impaired accommodation; taste and smell disorders; severe
      liver damage; worsening of myasthenia gravis; rhabdomyolysis; and loss of
      consciousness. Prolongation of the QT interval with standard oral doses is a
      worrisome adverse effect. In practice, it is better not to use telithromycin as
      it exposes patients to disproportionate, serious adverse effects. When treatment
      with a macrolide antibiotic appears necessary, it is prudent to choose a
      different macrolide, such as spiramycin or azithromycin, which have fewer adverse
      effects.

PMID- 25954794
TI  - Gabapentin and pregabalin: hepatic and haematological toxicity.
AB  - A review of pharmacovigilance data collected in France has shown that gabapentin
      and pregabalin are associated with serious and sometimes fatal hepatic and
      haematological disorders.

PMID- 25954796
TI  - Interferon alfa: retinal detachment.

PMID- 25954795
TI  - Pazopanib: pericardial effusion.

PMID- 25954797
TI  - Interferon alfa: hyperpigmentation.

PMID- 25954798
TI  - SSRI antidepressants in utero: pulmonary hypertension.

PMID- 25954799
TI  - Type 2 diabetes and metformin. First choice for monotherapy: weak evidence of
      efficacy but well-known and acceptable adverse effects.
AB  - Many guidelines recommend metformin as first-line therapy for patients with type
      2 diabetes. This recommendation is primarily based on the results of the Ukpds
      trial published in 1998. However, the methodology of this trial has been
      criticised. In 2014, does the harm-benefit balance of metformin still justify its
      first-line use in type 2 diabetes? To answer this question, we conducted a review
      of the literature using the standard Prescrire methodology. In the Ukpds trial,
      involving about 1700 overweight diabetic patients, metformin monotherapy for
      about 10 years was more effective in reducing mortality than glycaemic control
      based mainly on dietary measures, and also more effective than treatment with a
      sulphonylurea such as chlorpropamide or glibenclamide, or with insulin. However,
      these results are undermined by several methodological flaws. In the Adopt trial,
      in which about 4400 patients were followed for 4 years, metformin, glibenclamide
      and rosiglitazone did not have significantly different effects on the risk of
      death or cardiovascular events. A meta-analysis of ten randomised trials versus
      placebo or other hypoglycaemic drugs did not show that metformin monotherapy had
      a statistically significant effect on mortality. In the Cosmic trial, including
      more than 5000 patients, metformin monotherapy for one year was not more
      effective in reducing mortality than another oral hypoglycaemic drug. In the
      Spread-Dimcad trial in 304 diabetic patients with coronary artery disease,
      metformin monotherapy appeared to be more effective in preventing cardiovascular
      complications than glipizide after 5 years of follow-up. The adverse effects of
      metformin mainly consist of dose-dependent gastrointestinal disorders and rare
      cases or life-threatening lactic aciaosis. Kidney failure reduces metformin
      elimination. Metformin rarely causes hypoglycaemia and has no effect on body
      weight. It does not increase cancer-related mortality. It sometimes causes
      vitamin B12 deficiency leading to macrocytic anaemia or peripheral neuropathy.
      Metformin mainly carries a risk of interactions with drugs that impair renal
      function, such as non-steroidal anti-inflammatory drugs and iodinated contrast
      media. Renal failure can lead to metformin accumulation and an increased risk of
      lactic acidosis. In mid-2014, the only study to show a reduction in mortality and
      complications of diabetes remains the Ukpds trial. Taken together, the available
      data suggest that metformin monotherapy tends to reduce mortality and
      cardiovascular morbidity and mortality. Its adverse effects have been extensively
      studied and are acceptable provided renal function is monitored, especially in
      situations in which patients are at risk of kidney failure.The harm-benefit
      balance of metformin monotherapy remains favourable in most patients with type 2
      diabetes when dietary measures alone are not sufficient.

PMID- 25954800
TI  - Acetazolamide and prevention of acute mountain sickness.
AB  - When planning a rapid ascent to an altitude above 3000 metres, acetazolamide 250
      mg daily reduces the risk of acute mountain sickness, with generally moderate
      adverse effects.

PMID- 25954801
TI  - Determining the harm-benefit balance of an intervention: for each patient.
AB  - The decision on whether or not to offer a patient a medical, diagnostic,
      therapeutic or other type of intervention is mainly based on the harm-benefit
      balance of this intervention for that particular patient. The benefits that
      matter most are those that correspond to a tangible improvement for the patient
      rather than improvement in a surrogate end-point. The harms include the various
      potential or common adverse effects and drawbacks. The harm-benefit balance of an
      intervention is first evaluated at the population level. Evaluation of the
      benefits therefore takes into account the strength of the evidence obtained in
      clinical trials, the magnitude and probability of the benefits in these trials,
      and the profile of the patients enrolled. Evaluation of the harms involves
      identifying the drawbacks and amassing a body of evidence to determine potential
      adverse effects. Evaluation of the adverse effects also takes into account
      particular situations (age, pregnancy, concomitant diseases and treatments, etc.)
      and the probability and consequences of error. The harm-benefit balance cannot be
      reduced to an artificial, fixed mathematical ratio. Its assessment occasionally
      involves a degree of subjectivity. It is sometimes biased due to manipulation of
      the data. At the individual level, the harm-benefit balance depends on: the
      characteristics, objectives and values of each patient; the healthcare
      professionals involved and the medical and social environment. It is best
      evaluated in collaboration with the persons concerned, so that it can provide a
      basis for shared decision-making. The harm-benefit balance of an intervention can
      change. Its periodic re-assessment, taking into account new evidence and any
      changes in the patient's situation, provides an opportunity to re-examine the
      decisions taken, in the patient's best interests.

PMID- 25954802
TI  - Dare to refuse the exorbitant price of Sovaldi!

PMID- 25954803
TI  - Power Law Scaling in Human and Empty Room MEG Recordings.

PMID- 25954805
TI  - Correction: Deletion of the Mitochondrial Flavoprotein Apoptosis Inducing Factor
      (AIF) Induces beta-Cell Apoptosis and Impairs beta-Cell Mass.

PMID- 25954804
TI  - Natural Killer Cell Sensing of Infected Cells Compensates for MyD88 Deficiency
      but Not IFN-I Activity in Resistance to Mouse Cytomegalovirus.
AB  - In mice, plasmacytoid dendritic cells (pDC) and natural killer (NK) cells both
      contribute to resistance to systemic infections with herpes viruses including
      mouse Cytomegalovirus (MCMV). pDCs are the major source of type I IFN (IFN-I)
      during MCMV infection. This response requires pDC-intrinsic MyD88-dependent
      signaling by Toll-Like Receptors 7 and 9. Provided that they express appropriate
      recognition receptors such as Ly49H, NK cells can directly sense and kill MCMV
      infected cells. The loss of any one of these responses increases susceptibility
      to infection. However, the relative importance of these antiviral immune
      responses and how they are related remain unclear. In humans, while IFN-I
      responses are essential, MyD88 is dispensable for antiviral immunity. Hence, a
      higher redundancy has been proposed in the mechanisms promoting protective immune
      responses against systemic infections by herpes viruses during natural infections
      in humans. It has been assumed, but not proven, that mice fail to mount
      protective MyD88-independent IFN-I responses. In humans, the mechanism that
      compensates MyD88 deficiency has not been elucidated. To address these issues, we
      compared resistance to MCMV infection and immune responses between mouse strains
      deficient for MyD88, the IFN-I receptor and/or Ly49H. We show that selective
      depletion of pDC or genetic deficiencies for MyD88 or TLR9 drastically decreased
      production of IFN-I, but not the protective antiviral responses. Moreover, MyD88,
      but not IFN-I receptor, deficiency could largely be compensated by Ly49H-mediated
      antiviral NK cell responses. Thus, contrary to the current dogma but consistent
      with the situation in humans, we conclude that, in mice, in our experimental
      settings, MyD88 is redundant for IFN-I responses and overall defense against a
      systemic herpes virus infection. Moreover, we identified direct NK cell sensing
      of infected cells as one mechanism able to compensate for MyD88 deficiency in
      mice. Similar mechanisms likely contribute to protect MyD88- or IRAK4-deficient
      patients from viral infections. 

PMID- 25954806
TI  - Cognitive performance and cerebrospinal fluid biomarkers of neurodegeneration: a
      study of patients with bipolar disorder and healthy controls.
AB  - The purpose of the present study was to investigate if cerebrospinal fluid (CSF)
      biomarkers of neurodegeneration are associated with cognition in bipolar disorder
      and healthy controls, respectively. CSF concentrations of total and
      phosphorylated tau, amyloid beta (Abeta)1-42, ratios of Abeta42/40 and
      Abeta42/38, soluble amyloid precursor protein alpha and beta, and neurofilament
      light chain protein were analyzed in relation to neuropsychological performance
      in 82 euthymic bipolar disorder patients and 71 healthy controls. Linear
      regression models were applied to account for performance in five cognitive
      domains using the CSF biomarkers. In patients, the CSF biomarkers explained a
      significant proportion of the variance (15-36%, p=.002 - <.0005) in all cognitive
      domains independently of age, medication, disease status, and bipolar subtype I
      or II. However, the CSF biomarkers specifically mirroring Alzheimer-type brain
      changes, i.e., P-tau and Abeta1-42, did not contribute significantly. In healthy
      controls, CSF biomarkers did not explain the variance in cognitive performance.
      Selected CSF biomarkers of neurodegenerative processes accounted for cognitive
      performance in persons with bipolar disorder, but not for healthy controls.
      Specifically, the ratios of Abeta42/40 and Abeta42/38 were consistently
      associated with altered cognitive performance. 

PMID- 25954807
TI  - Correction: Indexes of Large Genome Collections on a PC.

PMID- 25954808
TI  - A Metabotropic-Like Flux-Independent NMDA Receptor Regulates Ca2+ Exit from
      Endoplasmic Reticulum and Mitochondrial Membrane Potential in Cultured
      Astrocytes.
AB  - Astrocytes were long thought to be only structural cells in the CNS; however,
      their functional properties support their role in information processing and
      cognition. The ionotropic glutamate N-methyl D-aspartate (NMDA) receptor (NMDAR)
      is critical for CNS functions, but its expression and function in astrocytes is
      still a matter of research and debate. Here, we report immunofluorescence (IF)
      labeling in rat cultured cortical astrocytes (rCCA) of all NMDAR subunits, with
      phenotypes suggesting their intracellular transport, and their mRNA were detected
      by qRT-PCR. IF and Western Blot revealed GluN1 full-length synthesis, subunit
      critical for NMDAR assembly and transport, and its plasma membrane localization.
      Functionally, we found an iCa2+ rise after NMDA treatment in Fluo-4-AM labeled
      rCCA, an effect blocked by the NMDAR competitive inhibitors D(-)-2-amino-5
      phosphonopentanoic acid (APV) and Kynurenic acid (KYNA) and dependent upon GluN1
      expression as evidenced by siRNA knock down. Surprisingly, the iCa2+ rise was not
      blocked by MK-801, an NMDAR channel blocker, or by extracellular Ca2+ depletion,
      indicating flux-independent NMDAR function. In contrast, the IP3 receptor (IP3R)
      inhibitor XestosponginC did block this response, whereas a Ryanodine Receptor
      inhibitor did so only partially. Furthermore, tyrosine kinase inhibition with
      genistein enhanced the NMDA elicited iCa2+ rise to levels comparable to those
      reached by the gliotransmitter ATP, but with different population dynamics.
      Finally, NMDA depleted the rCCA mitochondrial membrane potential (mDeltapsi)
      measured with JC-1. Our results demonstrate that rCCA express NMDAR subunits
      which assemble into functional receptors that mediate a metabotropic-like, non
      canonical, flux-independent iCa2+ increase. 

PMID- 25954809
TI  - Accuracy of image guidance using free-breathing cone-beam computed tomography for
      stereotactic lung radiotherapy.
AB  - Movement of the target object during cone-beam computed tomography (CBCT) leads
      to motion blurring artifacts. The accuracy of manual image matching in image
      guided radiotherapy depends on the image quality. We aimed to assess the accuracy
      of target position localization using free-breathing CBCT during stereotactic
      lung radiotherapy. The Vero4DRT linear accelerator device was used for the
      examinations. Reference point discrepancies between the MV X-ray beam and the
      CBCT system were calculated using a phantom device with a centrally mounted steel
      ball. The precision of manual image matching between the CBCT and the averaged
      intensity (AI) images restructured from four-dimensional CT (4DCT) was estimated
      with a respiratory motion phantom, as determined in evaluations by five
      independent operators. Reference point discrepancies between the MV X-ray beam
      and the CBCT image-guidance systems, categorized as left-right (LR), anterior
      posterior (AP), and superior-inferior (SI), were 0.33 +/- 0.09, 0.16 +/- 0.07,
      and 0.05 +/- 0.04 mm, respectively. The LR, AP, and SI values for residual errors
      from manual image matching were -0.03 +/- 0.22, 0.07 +/- 0.25, and -0.79 +/- 0.68
      mm, respectively. The accuracy of target position localization using the Vero4DRT
      system in our center was 1.07 +/- 1.23 mm (2 SD). This study experimentally
      demonstrated the sufficient level of geometric accuracy using the free-breathing
      CBCT and the image-guidance system mounted on the Vero4DRT. However, the inter
      observer variation and systematic localization error of image matching
      substantially affected the overall geometric accuracy. Therefore, when using the
      free-breathing CBCT images, careful consideration of image matching is especially
      important. 

PMID- 25954810
TI  - Phosphorylation of PPARgamma Affects the Collective Motions of the PPARgamma
      RXRalpha-DNA Complex.
AB  - Peroxisome-proliferator activated receptor-gamma (PPARgamma) is a nuclear hormone
      receptor that forms a heterodimeric complex with retinoid X receptor-alpha
      (RXRalpha) to regulate transcription of genes involved in fatty acid storage and
      glucose metabolism. PPARgamma is a target for pharmaceutical intervention in type
      2 diabetes, and insight into interactions between PPARgamma, RXRalpha, and DNA is
      of interest in understanding the function and regulation of this complex.
      Phosphorylation of PPARgamma by cyclin-dependent kinase 5 (Cdk5) has been shown
      to dysregulate the expression of metabolic regulation genes, an effect that is
      counteracted by PPARgamma ligands. We applied molecular dynamics (MD) simulations
      to study the relationship between the ligand-binding domains of PPARgamma and
      RXRalpha with their respective DNA-binding domains. Our results reveal that
      phosphorylation alters collective motions within the PPARgamma-RXRalpha complex
      that affect the LBD-LBD dimerization interface and the AF-2 coactivator binding
      region of PPARgamma. 

PMID- 25954811
TI  - Health and Masculinities Shaped by Agency within Structures among Young
      Unemployed Men in a Northern Swedish Context.
AB  - AIM: The aim of our paper was to explore expressions of life choices and life
      chances (aspects of agency within structures) related to power and experiences of
      health among early unemployed adolescent young men during the transition period
      to adulthood. These expressions of agency within structure were interpreted in
      the light of Cockerham's Health Lifestyles Theory. Furthermore, social
      constructions of masculinities were addressed in our analysis. METHODS: Repeated
      interviews with ten young men in a cohort of school leavers were analyzed with
      qualitative content analysis. RESULTS AND DISCUSSION: Cockerham's model was
      useful for interpreting our findings and we found disposition to act to be a
      crucial theoretical tool to capture the will and intentions of participants in
      relation to health. We developed the model in the following ways: structure and
      socialization were visualized as surrounding the whole model. Analyses of what
      enhances or restricts power are important. In addition to practices of health
      lifestyles, we added experiences of health as outcome as well as emotional
      aspects in disposition to act. We interpret our findings as constructions of
      masculinities within certain structures, in relation to choices, habitus and
      practices. CONCLUSIONS: Qualitative research could contribute to develop the
      understanding of the agency within structure relationships. Future studies need
      to pay attention to experiences of health among young people at the margin of the
      labor market in various milieus--and to analyze these in relation to gender
      constructions and within the frame-work of agency within structure.

PMID- 25954812
TI  - The Relationship between Alcohol Outlets, HIV Risk Behavior, and HSV-2 Infection
      among South African Young Women: A Cross-Sectional Study.
AB  - BACKGROUND: Alcohol consumption has a disinhibiting effect that may make sexual
      risk behaviors and disease transmission more likely. The characteristics of
      alcohol-serving outlets (e.g. music, dim lights, lack of condoms) may further
      encourage risky sexual activity. We hypothesize that frequenting alcohol outlets
      will be associated with HIV risk. METHODS: In a sample of 2,533 school-attending
      young women in rural South Africa, we performed a cross-sectional analysis to
      examine the association between frequency of alcohol outlet visits in the last
      six months and four outcomes related to HIV risk: number of sex partners in the
      last three months, unprotected sex acts in the last three months, transactional
      sex with most recent partner, and HSV-2 infection. We also tested for interaction
      by alcohol consumption. RESULTS: Visiting alcohol outlets was associated with
      having more sex partners [adjusted odds ratio (aOR), one versus zero partners
      (95% confidence interval (CI)): 1.51 (1.21, 1.88)], more unprotected sex acts
      [aOR, one versus zero acts (95% CI): 2.28 (1.52, 3.42)], higher levels of
      transactional sex [aOR (95% CI): 1.63 (1.03, 2.59)], and HSV-2 infection [aOR
      (95% CI): 1.30 (0.88, 1.91)]. In combination with exposure to alcohol
      consumption, visits to alcohol outlets were more strongly associated with all
      four outcomes than with either risk factor alone. Statistical evidence of
      interaction between alcohol outlet visits and alcohol consumption was observed
      for all outcomes except transactional sex. CONCLUSIONS: Frequenting alcohol
      outlets was associated with increased sexual risk in rural South African young
      women, especially when they consumed alcohol. Sexual health interventions
      targeted at alcohol outlets may effectively reach adolescents at high risk for
      sexually transmitted infections like HIV and HSV-2. TRIAL REGISTRATION: HIV
      Prevention Trials Network HPTN 068.

PMID- 25954813
TI  - Higher prevalence of human papillomavirus infection in adolescent and young adult
      girls belonging to different Indian tribes with varied socio-sexual lifestyle.
AB  - BACKGROUND: Despite high prevalence of human papillomavirus (HPV) infection and
      cervical cancer in Indian women, no study has been done in tribal populations
      whose socio-sexual lifestyle is different. Therefore, HPV screening has been
      carried out in pre-adolescent, adolescent and young adult tribal girls using self
      collected urine samples. METHODS: 20-35 ml self-collected midstream urine samples
      were obtained from a total of 2278 healthy tribal girls (9-25 years) comprising
      pre-adolescent, adolescent and young adults from three Indian states: Madhya
      Pradesh, Jharkhand and Chhattisgarh. beta-globin positive 2034 samples were
      employed for HPV detection and genotyping. RESULTS: The overall prevalence of HPV
      infection in tribal girls was 12.9% (262/2034). More than 65% (172/262) of them
      were infected with HR-HPV types of which HPV16 was the most predominant type
      (54%). Young adult girls aged 18-25 years showed a significantly higher
      prevalence of HPV infection (19.2%; OR = 3.36; 95% CI 2.97-6.34, P<0.001) as
      compared to that in adolescent (11.4%; OR = 1.82; 95% CI 1.20-2.76, P<0.01) or
      pre-adolescent girls (6.6%). CONCLUSION: This is a first study showing
      significantly a very high prevalence of HPV infection in adolescent and young
      adult tribal girls possibly due to different socio-sexual behavior, indicating a
      serious health concern for Indian tribal women.

PMID- 25954814
TI  - Clinical characteristics and risk factors of an outbreak with scrub typhus in
      previously unrecognized areas, Jiangsu province, China 2013.
AB  - Scrub typhus, caused by Orientia tsutsugamushi, has emerged recently in Jingjiang
      City, China where the disease had not been known to exist. We analyzed
      epidemiological data, clinical characteristics and risk factors of scrub typhus
      outbreak in Jingjiang City, 2013. The 271 clinically diagnosed patients were
      predominantly farmers 50 to 69 years old and the peak of onset was early to mid
      November. For the 187 laboratory-confirmed cases, the major clinical
      manifestations of the patients were fever (100%), eschar (88.2%), rash (87.7%),
      chills (87.7%), and headache (66.8%). A community-based case-control study was
      carried out to investigate the risk factors of the scrub typhus outbreak.
      Bundling or moving waste straw (OR=9.0, 95%CI 4.6-17.8) and living at the edge of
      village (OR=0.6, 95%CI 0.4-0.9) posed the highest risks through single- and multi
      variable conditional logistic regression. Phylogenetic analysis of the 56-kDa TSA
      gene showed that the new cluster (GB-C2) and the previously reported cluster (GB
      C1) of O. tsutsugamushi were associated with this outbreak. These findings are
      useful for the establishment of a detailed control strategy for scrub typhus
      infection in previously unrecognized areas of Jiangsu Province, China. 

PMID- 25954815
TI  - A Model for p38MAPK-Induced Astrocyte Senescence.
AB  - Experimental evidence indicates that aging leads to accumulation of senescent
      cells in tissues and they develop a secretory phenotype (also known as SASP, for
      senescence-associated secretory phenotype) that can contribute to chronic
      inflammation and diseases. Recent results have showed that markers of senescence
      in astrocytes from aged brains are increased in brains with Alzheimer's disease.
      These studies strongly involved the stress kinase p38MAPK in the regulation of
      the secretory phenotype of astrocytes, yet the molecular mechanisms underlying
      the onset of senescence and SASP activation remain unclear. In this work, we
      propose a discrete logical model for astrocyte senescence determined by the level
      of DNA damage (reparable or irreparable DNA strand breaks) where the kinase
      p38MAPK plays a central role in the regulation of senescence and SASP. The model
      produces four alternative stable states: proliferation, transient cycle arrest,
      apoptosis and senescence (and SASP) computed from its inputs representing DNA
      damages. Perturbations of the model were performed through gene gain or loss of
      functions and compared with results concerning cultures of normal and mutant
      astrocytes showing agreement in most cases. Moreover, the model allows some
      predictions that remain to be tested experimentally. 

PMID- 25954816
TI  - Pioglitazone increases whole body insulin sensitivity in obese, insulin-resistant
      rhesus monkeys.
AB  - Hyperinsulinemic-euglycemic clamps are considered the "gold standard" for
      assessing whole body insulin sensitivity. When used in combination with tracer
      dilution techniques and physiological insulin concentrations, insulin
      sensitization can be dissected and attributed to hepatic and peripheral
      (primarily muscle) effects. Non-human primates (NHPs), such as rhesus monkeys,
      are the closest pre-clinical species to humans, and thus serve as an ideal model
      for testing of compound efficacy to support translation to human efficacy. We
      determined insulin infusion rates that resulted in high physiological insulin
      concentrations that elicited maximal pharmacodynamic responses during
      hyperinsulinemic-euglycemic clamps. These rates were then used with [U-13C]-D
      glucose, to assess and document the degrees of hepatic and peripheral insulin
      resistance between healthy and insulin-resistant, dysmetabolic NHPs. Next,
      dysmetabolic NHPs were treated for 28 days with pioglitazone (3 mg/kg) and again
      had their insulin sensitivity assessed, illustrating a significant improvement in
      hepatic and peripheral insulin sensitivity. This coincided with a significant
      increase in insulin clearance, and normalization of circulating adiponectin. In
      conclusion, we have determined a physiological clamp paradigm (similar to humans)
      for assessing glucose turnover in NHPs. We have also demonstrated that insulin
      resistant, dysmetabolic NHPs respond to the established insulin sensitizer,
      pioglitazone, thus confirming their use as an ideal pre-clinical translational
      model to assess insulin sensitizing compounds.

PMID- 25954817
TI  - A Home-Based Educational Intervention Improves Patient Activation Measures and
      Diabetes Health Indicators among Zuni Indians.
AB  - INTRODUCTION: One in three people will be diagnosed with diabetes by 2050, and
      the proportion will likely be higher among Native Americans. Diabetes control is
      currently suboptimal in underserved populations despite a plethora of new
      therapies. Patient empowerment is a key determinant of diabetes control, but such
      empowerment can be difficult to achieve due to resource limitation and cultural,
      language and health literacy barriers. We describe a home-based educational
      intervention using Community Health Representatives (CHRs), leading to
      improvement in Patient Activation Measures scores and clinical indicators of
      diabetes control. METHODS: Sixty participants with type 2 diabetes (T2D)
      completed a baseline evaluation including physical exam, Point of Care (POC)
      testing, and the Patient Activation Measure (PAM) survey. Participants then
      underwent a one hour group didactic session led by Community Health
      Representatives (CHRs) who subsequently carried out monthly home-based
      educational interventions to encourage healthy lifestyles, including diet,
      exercise, and alcohol and cigarette avoidance until follow up at 6 months, when
      clinical phenotyping and the PAM survey were repeated. RESULTS: PAM scores were
      increased by at least one level in 35 (58%) participants, while 24 participants
      who started at higher baseline score did not change. Six months after
      intervention, mean levels of A1C decreased by 0.7 +/- 1.2%; fasting blood glucose
      decreased by 24.0 +/- 38.0 mg/dl; BMI decreased by 1.5 +/- 2.1 kg/m2; total
      cholesterol decreased by 12.0 +/- 28.0 mg/dl; and triglycerides decreased by 52.0
      +/- 71.0 mg/dl. All of these changes were statistically significant (p < 0.05).
      CONCLUSION: This six month, CHR led and community-oriented educational
      intervention helps inform standards of practice for the management of diabetes,
      engages diabetic populations in their own care, and reduces health disparities
      for the underserved population of Zuni Indians. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT02339311.

PMID- 25954818
TI  - Genetic polymorphisms of interleukin-16 and risk of knee osteoarthritis.
AB  - BACKGROUND: Interleukin-16 (IL-16), a pleiotropic cytokine, plays a fundamental
      role in inflammatory diseases. This study investigates the association between IL
      16 polymorphisms and the risk of knee osteoarthritis (OA) in a Chinese
      population. METHODS: The IL-16 rs11556218, rs4072111, and rs4778889 polymorphisms
      were determined in 150 knee OA cases and 147 healthy controls through polymerase
      chain reaction-restriction fragment length polymorphism. RESULTS: The results
      suggested that the variants in IL-16 gene rs11556218 site were associated with a
      decreased knee OA risk after adjusting for age, sex, BMI, and smoking and
      drinking status (TG vs. TT: OR, 0.69; 95% CI, 0.53-0.89; P = 0.006; GG vs. TT:
      OR, 0.64; 95% CI, 0.45-0.90; P = 0.042; dominant model: OR, 0.68; 95% CI, 0.29
      0.87; P = 0.002; G vs. T allele: OR, 0.77; 95% CI, 0.66-0.90; P = 0.003).
      Similarly, subjects bearing the rs4072111 variant genotypes and alleles also had
      a lower susceptibility to knee OA compared with those bearing the wild-type (CT
      vs. CC: OR, 0.66; 95% CI, 0.53-0.83; P = 0.002; TT vs. CC: OR, 0.57; 95% CI, 0.40
      0.82; P = 0.027; dominant model: OR, 0.65; 95%, CI 0.52-0.80; P <0.001; T vs. C
      allele: OR, 0.69; 95% CI, 0.58-0.81; P <0.001). Further, the C allele and the
      combined genotype (CC+CT) of rs4778889 were associated with a slightly decreased
      risk of knee OA. In addition, we found two high-risk haplotypes: TTT (OR, 3.70)
      and GCC (OR, 6.22). Finally, serum IL-16 levels of knee OA patients were
      significantly higher than those of controls (P = 0.001). CONCLUSIONS: Despite the
      small sample size, this is the first study suggesting IL-16 gene polymorphisms to
      be associated with the risk of knee OA.

PMID- 25954819
TI  - A comparison of phenotypic traits related to trypanotolerance in five west
      african cattle breeds highlights the value of shorthorn taurine breeds.
AB  - BACKGROUND: Animal African Trypanosomosis particularly affects cattle and
      dramatically impairs livestock development in sub-Saharan Africa. African Zebu
      (AFZ) or European taurine breeds usually die of the disease in the absence of
      treatment, whereas West African taurine breeds (AFT), considered trypanotolerant,
      are able to control the pathogenic effects of trypanosomosis. Up to now, only one
      AFT breed, the longhorn N'Dama (NDA), has been largely studied and is considered
      as the reference trypanotolerant breed. Shorthorn taurine trypanotolerance has
      never been properly assessed and compared to NDA and AFZ breeds.
      METHODOLOGY/PRINCIPAL FINDINGS: This study compared the
      trypanotolerant/susceptible phenotype of five West African local breeds that
      differ in their demographic history. Thirty-six individuals belonging to the
      longhorn taurine NDA breed, two shorthorn taurine Lagune (LAG) and Baoule (BAO)
      breeds, the Zebu Fulani (ZFU) and the Borgou (BOR), an admixed breed between AFT
      and AFZ, were infected by Trypanosoma congolense IL1180. All the cattle were
      genetically characterized using dense SNP markers, and parameters linked to
      parasitaemia, anaemia and leukocytes were analysed using synthetic variables and
      mixed models. We showed that LAG, followed by NDA and BAO, displayed the best
      control of anaemia. ZFU showed the greatest anaemia and the BOR breed had an
      intermediate value, as expected from its admixed origin. Large differences in
      leukocyte counts were also observed, with higher leukocytosis for AFT.
      Nevertheless, no differences in parasitaemia were found, except a tendency to
      take longer to display detectable parasites in ZFU. CONCLUSIONS: We demonstrated
      that LAG and BAO are as trypanotolerant as NDA. This study highlights the value
      of shorthorn taurine breeds, which display strong local adaptation to
      trypanosomosis. Thanks to further analyses based on comparisons of the genome or
      transcriptome of the breeds, these results open up the way for better knowledge
      of host-pathogen interactions and, furthermore, for identifying key biological
      pathways.

PMID- 25954820
TI  - Enhancing Thermal Stability and Lifetime of Solid-State Dye-Sensitized Solar
      Cells via Molecular Engineering of the Hole-Transporting Material Spiro-OMeTAD.
AB  - Thermal stability of hybrid solar cells containing spiro-OMeTAD as hole
      transporting layer is investigated. It is demonstrated that fully symmetrical
      spiro-OMeTAD is prone to crystallization, and growth of large crystalline domains
      in the hole-transporting layer is one of the causes of solar cell degradation at
      elevated temperatures, as crystallization of the material inside the pores or on
      the interface affects the contact between the absorber and the hole transport.
      Suppression of the crystal growth in the hole-transporting layer is demonstrated
      to be a viable tactic to achieve a significant increase in the solar cell
      resistance to thermal stress and improve the overall lifetime of the device.
      Findings described in this publication could be applicable to hybrid solar cell
      research as a number of well-performing architectures rely heavily upon doped
      spiro-OMeTAD as hole-transporting material. 

PMID- 25954821
TI  - Quality Measures for Community-Based, Rural Palliative Care Programs in
      Minnesota: A Pilot Study.
AB  - BACKGROUND: Despite the growth of palliative care programs in many urban areas,
      palliative care programs remain less common in rural communities. As more
      community-based programs emerge, particularly in rural areas, it will be
      important to establish a standard set of quality measures that are useful for
      improving care and feasible for program evaluation. OBJECTIVES: The study's
      objective was to identify and field test a standard set of quality measures for
      rural, community-based palliative care programs that reflect clinical quality,
      patient and family experience, and impact on inpatient and emergency department
      utilization. METHODS: A pilot program was conducted to test standardized quality
      measures for rural, community-based programs. Measures were identified through
      review of existing measures and input from experts in palliative care and rural
      health services. The study was carried out in 2012 and 2013 in five community
      based palliative care programs from rural communities. A total of 138 palliative
      care patients were included. Measurements were chart abstraction, patient and
      family experience surveys, patient-level health care utilization, and program
      level operations surveys. Phone interviews with each participating program were
      performed at the study's end. RESULTS: The participating programs found the
      measures feasible to collect, and the information they provided aided in
      assessment, comparison of structure, and process improvement for care delivery.
      Program staff suggested additional potential measures and expressed their desire
      to track the measures beyond the pilot time frame. CONCLUSION: The standard
      measures developed and tested were deemed feasible to collect and useful for all
      five participating rural, community-based palliative care programs.

PMID- 25954822
TI  - Laser beam coupling into nerve fiber myelin allows one to assess its structural
      membrane properties.
AB  - We show that myelin, the insulation wrap of nerve fibers, can couple laser light,
      thus behaving as a single-cell optical device. The effect was employed to map
      distinct myelin regions based on the coupling efficiency. Raman spectra
      acquisition allowed us to simultaneously understand the underlying microscopic
      differences in the membrane lipid ordering degree. The described method
      potentially provides new capabilities in myelin-associated disease studies and
      can be used as a handy tool for myelin structure investigation in combination
      with other methods.

PMID- 25954823
TI  - Changes in capillary diameters in pregnancy-induced hypertension.
AB  - OBJECTIVE: To compare capillary diameters, density and reactivity in high-risk
      pregnancies complicated by pregnancy-induced hypertension (PIH) to other high
      risk pregnancies not affecting microcirculation (O). METHODS: Patients
      hospitalized at a tertiary referral center from January to May 2012 were enrolled
      in the prospective pilot study. Five microscopic fields were recorded from the
      nailfold for capillary diameters and functional capillary density assessment. One
      microscopic field was assessed before and after venous congestion to evaluate the
      change in capillary diameters. The results were expressed as median
      (interquartile range). Wilcoxon rank-sum test was used for the analysis of
      statistical significance (level of significance was set to p < 0.05). RESULTS: In
      total, 31 patients were available for statistical analysis (PIH = 17;O = 14).
      Patients in the PIH group had significantly longer capillaries (123(91;182) vs.
      72(65;107)MUm, p = 0.003) and higher average capillary diameter (12(10;13) vs.
      10(9;11)MUm, p = 0.017). The difference in mean functional capillary density was
      not significant (20(17;25) vs. 19(15:21), p > 0.05), however, significantly
      reduced capillary recruitment (1(0;7) vs. 10(6;17), p = 0.006) was found in PIH.
      Preeclampsia was observed in 10 patients from the PIH group. These patients did
      not significantly differ from the rest of the PIH group in the abovementioned
      variables. CONCLUSION: This is the first pilot study concerning change of
      capillary diameters after venous congestion in pregnancy. The reduced capillary
      recruitment and reduced capability of further dilation of capillaries after
      venous congestion observed in women with PIH may suggest a significantly reduced
      functional capacity of the microcirculation and increased load on capillary
      endothelium in pregnancy complicated by gestational hypertension.

PMID- 25954824
TI  - A modified Delphi method to create a scoring system for assessing team
      performance during maternal cardiopulmonary arrest.
AB  - BACKGROUND: Maternal cardiopulmonary arrest is a rare but often fatal emergency.
      The authors used a modified Delphi method to create a checklist of tasks for
      practitioners. METHODS: Within each round, experts ranked tasks on a scale from
      zero through five. Consensus was defined a priori as 80% exact agreement.
      RESULTS: Three rounds were required to achieve consensus resulting in a checklist
      of 45 tasks. Round One results revealed five tasks, Round Two included 25 tasks,
      and Round Three resulted in 29 tasks with 80% exact agreement. CONCLUSIONS: The
      modified Delphi method resulted in a weighted scoring system that can be used to
      objectively assess team performance.

PMID- 25954825
TI  - Prevalence of hypertensive disorders in women after preeclamptic pregnancy
      associated with decidual vasculopathy.
AB  - OBJECTIVE: A subgroup of preeclamptic women has spiral artery lesions termed
      decidual vasculopathy (DV) which relate to worse clinical outcome. We aimed to
      determine whether a history of preeclampsia (PE) with DV is associated with
      adverse overall and future pregnancy outcome, including increased recurrence risk
      of hypertensive diseases of pregnancy. METHODS: Via posted survey women with PE
      and DV (DV positive) in the index pregnancy were compared to those without the
      lesions (DV negative) on overall and future pregnancy outcome. RESULTS: DV
      positive cases showed a higher incidence of chronic hypertension both
      preconceptionally and at time of survey, adjusted odds ratio 4.8 (2.0-11.9). The
      DV positive group had a higher overall incidence of pregnancies with gestational
      hypertension (22% vs 13%, p = 0.04), preterm birth (59% vs 45%, p = 0.02) and a
      lower birth weight centile (30 vs 39, p = 0.02). There was no difference in
      outcome of future pregnancies, irrespective of the use of prophylactic aspirin.
      CONCLUSION: Women with DV-associated PE have a higher overall incidence of
      adverse obstetric outcome and of chronic hypertension, indicating an underlying
      vascular pathology, putting them at risk for pregnancy and cardiovascular
      complications. These women constitute a target group for counseling, monitoring
      and possibly lifestyle or pharmacological interventions.

PMID- 25954826
TI  - Healing of diabetic ulcers using photobiomodulation.

PMID- 25954827
TI  - O2 and Ca(2+) fluxes as indicators of apoptosis induced by rose bengal-mediated
      photodynamic therapy in human oral squamous carcinoma cells.
AB  - OBJECTIVE: Photodynamic therapy (PDT) triggers various cellular responses and
      induces cell death via necrosis and/or apoptosis. This study evaluated the
      feasibility of using O2 and Ca(2+) fluxes as indicators of apoptosis induced by
      rose bengal (RB)-mediated PDT in human oral squamous carcinoma cells (Cal27
      cells). METHODS: Intracellular reactive oxygen species (ROS) generation was
      assessed by the dichloro-dihydro-fluorescein diacetate (DCFH-DA) method. Real
      time O2 and Ca(2+) flux measurements were performed using the noninvasive micro
      test technique (NMT). Apoptosis of the PDT-treated cells was confirmed by 4'6
      diamidino-2-phenylindole-dilactate staining. The activation of apoptosis-related
      molecules was examined using Western blot. We assayed the effects of the
      fluctuation of O2 and Ca(2+) flux in response to PDT and the apoptotic mechanism,
      by which ROS, O2, and Ca(2+) synergistically may trigger apoptosis in PDT-treated
      cells. RESULTS: Real-time O2 and Ca(2+) flux measurements revealed that these
      indicators were involved in the timely regulation of apoptosis in the PDT-treated
      cells and were activated 2 h after PDT treatment. RB-mediated PDT significantly
      elicited the generation of ROS by approximately threefold, which was critical for
      PDT-induced apoptosis. Cytochrome c and cleaved caspase-3, caspase-9 and poly ADP
      ribose polymerase (PARP) were overexpressed, and the data provided evidence that
      2 h was considered to be the key observation time in RB-mediated PDT-induced
      apoptosis in Cal27 cells. CONCLUSIONS: Our collective results indicated that the
      effects of O2 and Ca(2+) fluxes may act as a real-time biomonitoring system of
      apoptosis in the RB-PDT-treated cells. Also, RB-mediated PDT can be a potential
      and effective therapeutic modality in oral squamous cell carcinoma.

PMID- 25954828
TI  - Chemical and Morphological Changes of Primary Teeth Irradiated with Nd:YAG Laser:
      An Ex Vivo Long-Term Analysis.
AB  - OBJECTIVE: The aim of this study was to assess any long-term chemical and
      morphological Nd:YAG laser modifications on irradiated primary enamel. BACKGROUND
      DATA: Previous studies on irradiated primary human enamel employed methodologies
      that evaluated the short-term effects only. METHODS: One hundred and eighty-six
      irradiated (with and/or without fluoride) primary enamel teeth from high-caries
      risk children, which were exfoliated over a 1-year period, were collected, and
      the sample surface area was submitted for scanning electron microscopy (SEM),
      Fourier transform infrared (FTIR) spectroscopy, and X-ray energy-dispersive
      spectrometry (EDS). The subsurface was analyzed by Knoop microhardness and light
      microscopy (LM). Data were analyzed by one way ANOVA and Tukey tests (alpha=0.05)
      and Kruskall-Wallis and Tukey tests (alpha=0.05). RESULTS: FTIR analysis revealed
      a higher concentration of phosphate and carbonate in the irradiated (0.987+/
      0.064) and lower concentration in the control groups (1.477+/-0.310). SEM
      analysis showed that the control samples exhibited a slightly smoother surface
      than the irradiated groups. The EDS analysis did not show any differences in the
      amount of calcium, phosphorus, or fluoride among the groups. The microhardness
      analysis revealed that sealant (249.86+/-7.15) and laser irradiation (262.44+/
      22.69) led to higher hardness values than the negative control group (128.35+/
      25.19). LM indicated significantly reduced caries formation in the laser (5.35+/
      5.38%) and the laser plus acidulated phosphate fluoride (APF) groups (10.35+/
      0.88%) compared with the negative control group (72.56+/-12.86%). CONCLUSIONS:
      Even with the limitations of the present study, these results suggest that Nd:YAG
      irradiation clinically modified the chemical composition of the enamel surface
      regardless of fluoride concentration, which successfully inhibited
      demineralization of primary tooth enamel over a 1-year period without significant
      morphological changes.

PMID- 25954829
TI  - Flash-lamp pulsed-dye laser treatment of keloids: results of an observational
      study.
AB  - OBJECTIVE: Flash lamp pulsed dye laser (FPDL) was used in a selected group of
      patients with hypertrophic scars and keloids. Objective of the study was to
      assess the efficacy on a large number of cases. BACKGROUND DATA: FPDL is a
      nonablative technology, typically used in vascular malformation therapy because
      of its specificity for hemoglobin. METHODS: A total of 59 patients (33 males and
      26 females, mean age 37.5 years) affected by hypertrophic postsurgical scars and
      keloids, underwent from four to six treatment sessions with a flash lamp pumped
      pulsed dye laser. Clinical follow-up was performed 6 months after the last
      treatment. Results were judged by blind observers. RESULTS: A total of 29
      patients out of 59 (49.1%) achieved excellent clearance, 15 patients (25.4%)
      achieved good to moderate clearance, and 12 patients (20.4%) obtained slight
      improvement. Only three subjects (5%) had little or no removal of their lesion.
      Treatment was well tolerated with minor and transient side effects. CONCLUSIONS:
      FPDL is known as a safe and effective treatment for different dermatological
      lesions in which skin microvessels play a key role in pathogenesis or
      development. This laser was effective when applied to hypertrophic scars and
      keloids. Further studies in a larger set of patients, however, are required to
      assess a standardized and reproducible method for treating these lesions.

PMID- 25954830
TI  - Blue Laser Inhibits Bacterial Growth of Staphylococcus aureus, Escherichia coli,
      and Pseudomonas aeruginosa.
AB  - OBJECTIVE: The purpose of this study was to analyze the influence of blue laser
      on bacterial growth of the main species that usually colonize cutaneous ulcers,
      as well as its effect over time following irradiation. BACKGROUND DATA: The use
      of blue laser has been described as an adjuvant therapeutic method to inhibit
      bacterial growth, but there is no consensus about the best parameters to be used.
      METHODS: Strains of Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC
      27853, and Escherichia coli ATCC 25922 were suspended in saline solution at a
      concentration of 1.5*10(3) colony forming units (CFU)/mL. Next, 300 MUL of this
      suspension was transferred to a microtitulation plate and exposed to a single
      blue laser irradiation (450 nm) at fluences of 0 (control), 3, 6, 12, 18, and 24
      J/cm(2). Each suspension was spread over the surface of a Petri plate before
      being incubated at 37 degrees C, and counts of CFU were determined after 24 and
      48 h. RESULTS: Blue laser inhibited the growth of S. aureus and P. aeruginosa at
      fluences >6 J/cm(2). On the other hand, E. coli was inhibited at all fluences
      tested, except at 24 J/cm(2). CONCLUSIONS: Blue laser light was capable of
      inhibiting bacterial growth at low fluences over time, thus presenting no time
      dependent effect.

PMID- 25954831
TI  - Current indications of low-level laser therapy in plastic surgery: a review.
AB  - OBJECTIVE: The aim of this comprehensive review is assess the relevant
      indications of LLLT in plastic surgery. BACKGROUND DATA: Low-level laser therapy
      (LLLT) is a safe adjunct treatment for a myriad indications such as pain,
      musculoskeletal disorders, or oral mucositis in cancer patients. METHODS: A
      systematic literature review was performed using the automated computerized
      PubMed search, with the key words low-level laser therapy and plastic surgery. In
      vivo and in vitro comparative studies conducted in humans or animals were
      included. A total of 113 articles were retrieved for screening, and 40 articles
      were analyzed for data extraction: 28 on animals and 12 on humans. RESULTS:
      Thirteen studies on animals showed that LLLT had efficacy in the improvement of
      flap survival. LLLT on a single spot over the pedicle area of the flap or near
      the base of the flap seemed to be superior to multi-irradiation. Also, LLLT
      seemed to improve chronic burn scars in humans, and acute wound healing in
      animals. CONCLUSIONS: On the contrary, LLLT cannot be considered as a valid
      therapeutic option for venous ulcers. The published studies on alopecia did not
      show that LLLT had efficacy for this indication, and on skin aging only two
      studies are reported showing that LLLT globally improved aging of skin. No side
      effects have been reported. More comparative studies are needed to validate and
      widen the medical indications of LLLT in plastic surgery.

PMID- 25954832
TI  - A Direct Metal-Free Decarboxylative Sulfono Functionalization (DSF) of Cinnamic
      Acids to alpha,beta-Unsaturated Phenyl Sulfones.
AB  - A metal-free room temperature decarboxylative cross-coupling between cinnamic
      acids and arylsulfonyl hydrazides has been realized for the first time for the
      synthesis of (E)-vinyl sulfones. The scope and versatility of the reaction has
      been demonstrated by the regio- and stereoselective synthesis of 22 derivatives
      with diverse structural features. 

PMID- 25954834
TI  - The Journal of Athletic Training: Volume 50!

PMID- 25954833
TI  - Single nucleotide polymorphisms in premature ovarian failure-associated genes in
      a Chinese Hui population.
AB  - Premature ovarian failure (POF) is an ovarian defect characterized by the
      premature depletion of ovarian follicles in individuals <40 years old, and is a
      major cause of infertility in females. Genetic factors are considered to be
      responsible for the development of POF, however, the exact pathogenesis remains
      to be elucidated in the majority of cases. In the present study, the single
      nucleotide polymorphisms (SNPs) of growth differentiation factor 9 (GDF9), bone
      morphogenetic protein 15 (BMP15), inhibin betaB (INHBB) and follicle stimulating
      hormone receptor (FSHR) genes were investigated, and their association with POF
      in a Chinese Hui population of the Ningxia Hui Autonomous Region in western China
      was evaluated. Peripheral blood samples were collected from 63 patients diagnosed
      with POF (POF group) and 58 normal control individuals (control group), from
      which the genomic DNA was isolated. The GDF9, BMP15, INHBB and FSHR genes were
      amplified using polymerase chain reaction assays, and their SNPs were determined
      by sequencing. In the four SNPs identified across the GDF9 loci, D57Y (169G>T),
      rs1049127 (546G>A), rs254286 (447C>T) and rs254285 (969C>G), the frequencies of
      the 546G>A genotype and allele A were significantly higher in the POF group,
      compared with the normal control group (34.92, vs. 6.90%; P<0.05 and 19.05, vs.
      3.23%; P<0.05, respectively), while no significant differences were observed in
      the occurrence of the c.447C>T and c.969C>G mutations between the two groups
      (60.32, vs. 50% and 50.79, vs. 55.17%, respectively). The c.169G>T mutation
      within the GDF9 gene was only detected in two patients with POF, and the mutation
      did not occur in the normal control group. A total of three SNPs were detected
      within the BMP15 gene, including rs3810682 (-9C>G), rs79377927 (788_789insTCT)
      and rs17003221 (852C>T), and no significant differences were observed in the
      frequencies of the -9C>G and 852C>T genotypes between the POF and control groups
      (7.94, vs. 6.90% and 4.76, vs. 3.45%, respectively). The 788_789insTCT genotype
      was detected in only two patients with POF. A novel mutation, c.1095C>A, was
      identified in exon 2 of the INHBB gene, however, no significant difference was
      found in the occurrence of the mutation between the two groups (30.16, vs.
      22.41%; P>0.05). The rs6165 (919G>A) and rs6166 (2039G>A) SNPs were detected in
      exon 10 of the FSHR gene; however, no significant difference was observed in the
      genotype frequencies between the two groups (92.06, vs. 91.38% and 96.83, vs.
      93.10%, respectively). These results demonstrated that GDF9 c.169G>T (D57Y),
      c.546G>A (rs1049127), and BMP15 rs79377927 (788_789insTCT) were associated with
      POF in the Chinese Hui population.

PMID- 25954835
TI  - Interaction of L-Cysteine with ZnO: Structure, Surface Chemistry, and Optical
      Properties.
AB  - Zinc oxide (ZnO) nanoparticles (NPs) were stabilized in water using the amino
      acid l-cysteine. A transparent dispersion was obtained with an agglomerate size
      on the level of the primary particles. The dispersion was characterized by
      dynamic light scattering (DLS), pH dependent zeta potential measurements,
      scanning transmission electron microscopy (STEM), X-ray diffraction (XRD),
      Fourier transform infrared (FTIR) spectroscopy, Raman spectroscopy,
      photoluminescence (PL) spectroscopy, and X-ray absorption fine structure (EXAFS,
      XANES) spectroscopy. Cysteine acts as a source for sulfur to form a ZnS shell
      around the ZnO core and as a stabilizer for these core-shell NPs. A large effect
      on the photoluminescent properties is observed: the intensity of the defect
      luminescence (DL) emission decreases by more than 2 orders of magnitude, the
      intensity of the near band edge (NBE) emission increases by 20%, and the NBE
      wavelength decreases with increasing cysteine concentration corresponding to a
      blue shift of about 35 nm due to the Burstein-Moss effect.

PMID- 25954836
TI  - The Effect of Coenzyme Q10 (Ubiquinone) on Random Pattern Skin Flap Survival in
      Rat Model.
AB  - BACKGROUND: In this study, the effect of coenzyme Q10 (CQ10) on flap survival was
      investigated. METHODS: Fifty Wistar Albino rats were divided into 5 groups. The
      survival rates of the skin flaps were assessed 10 days after complete elevation
      of the flaps. Regions of survival and necrosis were drawn on transparent acetate
      sheets and scanned into a computer. Tissue samples were assessed
      histopathologically after staining with hematoxylin-eosin, vascular endothelial
      growth factor staining and terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate-Biotin Nick End-labeling staining. To evaluate the
      antioxidant effect of CQ10; malondialdehyde, nitric oxide levels were measured.
      RESULTS: Viable flaps area was found higher in groups 3 and 4 as compared to
      groups 1, 2, and 5. In terms of vascular proliferation, elevated angiogenesis was
      observed in pathological specimens of groups 3 and 4 as compared to groups 1, 2,
      and 5. Malondialdehyde levels in groups 3 and 4 were found to be significantly
      decreased as compared to groups 1, 2 and 5 (P < 0.05). Moreover, serum levels of
      CQ10 were found significantly increased in groups 3 and 4 (P < 0.05).
      CONCLUSIONS: In conclusion, CQ10 significantly improves flap viability in rat
      model, and the highest levels of serum CQ10 can be obtained by oral
      administration.

PMID- 25954837
TI  - Advanced Age Does Not Worsen Recovery or Long-Term Morbidity After Postmastectomy
      Breast Reconstruction.
AB  - PURPOSE: Despite evidence that older women have quality-of-life outcomes similar
      to younger women after postmastectomy breast reconstruction (PMBR), they rarely
      receive it. There is a perception that PMBR in older women may result in
      significant physical morbidity. However, the effects of age on physical morbidity
      after PMBR have not been studied. This study sought to assess perceptions of
      recovery from surgery and long-term chest and upper body morbidity in older women
      who receive PMBR. METHODS: Women with American Joint Committee on Cancer stage 0
      III breast cancer who underwent a mastectomy with PMBR between 2005 and 2011 were
      surveyed to assess their functional health status (DUKE), physical well-being
      (BREAST-Q), and perceptions of recovery from surgery. Patients were stratified
      into 2 age groups: older (>=65 years) and younger (<65 years). Outcome scores
      were compared by mastectomy laterality, reconstruction type, and between age
      groups. Data were analyzed using chi2 and t tests. RESULTS: One hundred eight
      older and 103 younger patients returned surveys (response rate, 75.4%). The
      median time from mastectomy to survey was 4 years (range, 1-7). Younger women
      were more likely to undergo bilateral mastectomy than older women (65.7% vs
      32.2%, P < 0.001). Some women (66.9%) underwent implant-only reconstruction and
      33.1% underwent autologous reconstruction; there were no significant differences
      in reconstruction type between age groups. Patients who underwent unilateral and
      bilateral mastectomy had similar mean BREAST-Q physical well-being scores (79.4
      vs 78.9, respectively, P = 0.85). There was no difference in mean physical well
      being scores between older and younger patients (80.0 vs 78.5, respectively, P =
      0.61). In addition, older patients were less likely to perceive their recovery
      from PMBR as being difficult than younger patients, though this was not
      statistically significant (48.2% vs 64.3%, P = 0.07). CONCLUSIONS: Older women
      who undergo PMBR have physical and upper body well-being that is similar to
      younger women. In addition, their perception of recovery from PMBR is at least as
      good as that seen in younger women. Older women contemplating PMBR should be
      counseled that they are not at higher risk for long-term physical and upper body
      morbidity from PMBR than are younger women.

PMID- 25954838
TI  - Professional Burnout Among Plastic Surgery Residents: Can it be Prevented?
      Outcomes of a National Survey.
AB  - BACKGROUND: Plastic surgery residencies require significant investments of time
      and psychological resources. We herein determine the prevalence of burnout
      syndrome among plastic surgery residents and identify potentially protective
      factors. METHODS: A national cross-sectional study was conducted among French
      plastic surgery residents in March 2013. We distributed a validated measure of
      burnout (Maslach Burnout Inventory) in addition to a general questionnaire
      collecting sociodemographic and professional information. RESULTS: Fifty-two
      residents (61%) responded; their mean age was 29 years. A total of 25% and 13.5%
      of residents scored highly on the depersonalization and high-level emotional
      exhaustion burnout subscales, respectively, and 48.1% indicated perceived low
      level personal accomplishment. The occurrence of a weekly ward round by a senior
      surgeon (reported by 67.3% of respondents) appears to protect against burnout (P
      = 0.007); regular staff meetings in the unit (75% of respondents) were also
      protective because they limited depersonalization (P = 0.048) and promoted
      personal accomplishment (P = 0.031). The number of hours worked/week was not
      significantly associated with burnout. Despite these data, 69.2% reported
      satisfaction with their careers. CONCLUSIONS: Almost one third of plastic surgery
      residents exhibited a high degree of burnout; the risks were increased by being
      in the early years of training, feeling dissatisfied with career plans, and
      working in units in which senior surgeons did not make weekly ward rounds and in
      which regular staff meetings, which offer the opportunity to discuss cases or
      problems with other professionals, were not scheduled. Burnout increases the risk
      of medical errors and suicide among residents. Therefore, we suggest that
      screening for burnout is essential.

PMID- 25954839
TI  - Isolated Autologous Free Fat Grafting for Management of Facial Contour Asymmetry
      in a Subset of Growing Patients With Craniofacial Microsomia.
AB  - BACKGROUND: To report autologous free fat grafting as an isolated procedure to
      manage facial contour asymmetry of a subset of growing patients with craniofacial
      microsomia (CFM). METHODS: A retrospective analysis of CFM patients (n = 11) with
      low socioeconomic and intellectual status, poor oral hygiene, living far from our
      center, Pruzansky-Kaban I/II mandibles, without functional concerns, and with no
      craniofacial skeletal surgery who underwent isolated free fat grafting between
      2012 and 2013 was conducted. Surgeon and parent/patient satisfaction were
      elicited. Computerized photogrammetric quantitative and qualitative facial
      symmetry analyses were performed. RESULTS: All patients underwent isolated
      autologous free fat grafting to restore the facial contour symmetry. Surgeon and
      patient/parent were mostly satisfied. There were significant (all P < 0.05)
      postoperative quantitative facial symmetry enhancement and an overall qualitative
      facial symmetry enhancement. CONCLUSIONS: A significant improvement of facial
      symmetry was obtained in this subset of growing CFM patients using only isolated
      free fat grafting.

PMID- 25954840
TI  - Benefits of the Retrocaruncular Approach to the Medial Orbit: A Clinical And
      Anatomic Study.
AB  - BACKGROUND: Current trends in the management of medial orbital wall fractures are
      toward the development of transconjunctival incisions and the use of endoscopic
      assisted methods. Different authors have suggested variations of the medial
      transconjunctival approach. METHODS: (1) In 30 fresh cadaver orbits, the classic
      transcaruncular approach was compared with the precaruncular and retrocaruncular
      approach under magnified dissection. (2) A retrospective analysis was conducted
      on a series of 20 consecutive patients that underwent primary repair of medial
      orbital wall fractures using a retrocaruncular approach without endoscopic
      assistance. Postoperative computed tomography scans were obtained for all
      patients and were evaluated by 3 experienced clinicians. RESULTS: (1) Anatomic
      dissections showed that all 3 approaches provided excellent exposure of the
      entire medial orbital wall. The transcaruncular and precaruncular approaches,
      however, (a) both resulted in exposure of the upper and lower tarsi when
      incisions greater than 10 mm were used; (b) both required a transition from the
      preseptal plane to the postseptal plane when combined with inferior fornix
      incisions. (2) A clinical study of 20 patients showed all reconstructions were
      possible without endoscopic assistance, resulting in no postoperative
      complications. Postoperative computed tomography scans showed anatomic orbital
      reconstruction in all patients judged as excellent by the clinicians.
      CONCLUSIONS: Medial orbital wall fractures can be successfully repaired using
      transconjunctival incisions without using endoscopes. The retrocaruncular
      approach surpasses the transcaruncular and precaruncular methods due to its
      decreased risk of postoperative lid complications and its ability to be directly
      carried to the inferior conjunctival fornix.

PMID- 25954841
TI  - Evaluation of 2 novel devices for calculation of fluid requirements in pediatric
      burns.
AB  - OBJECTIVES: The Parkland formula for maintenance and resuscitation fluid
      requirements in the first 24 hours after pediatric burns is widely used, but
      calculation errors frequently occur. Two different novel aids to calculation, a
      dedicated electronic device and a mechanical disc calculator, are described and
      compared with the conventional method of calculation (pen and paper, assisted by
      a general purpose calculator). METHODS: In a blinded randomized volunteer study,
      21 participants performed a total of 189 calculations using simulated patient
      data to compare the accuracy and speed of 3 different methods for calculating
      resuscitation fluid requirements based on the pediatric Parkland formula. Bespoke
      software generated the simulated patient data and recorded accuracy and speed of
      all participant responses. RESULTS: Sixty-five percent of calculations with the
      electronic device, 35% using the disc and 44% using the pen/paper methods were
      within +/-5% of the correct value and considered "correct" for clinical purposes.
      The method used strongly affected the tendency to make errors (logistic
      regression). With thresholds of error magnitude classed as very small (>5%),
      small (>25%), medium (>50%) and large (>100%) of the correct value respectively,
      the electronic method produced fewer errors than both disc and pen/paper methods
      at all error thresholds. Disc produced more errors than pen/paper at the greater
      than 5% threshold but fewer at the greater than 25%, greater than 50%, and
      greater than 100% thresholds. CONCLUSIONS: Both novel devices provide safer and
      faster alternatives to conventional methods for calculation of fluid requirements
      in pediatric burns.

PMID- 25954842
TI  - An Adjustable-Traction Technique for Correction of Inverted Nipples.
AB  - BACKGROUND: Inverted nipples are a common problem in female patients. This
      deformity impairs the function and appearance of the breast and may cause
      psychological distress. Existing correctional techniques may result in nipple
      necrosis, recurrence, infection, and scarring. In this study, we evaluated the
      efficacy of a minimally invasive inverted nipple correction method involving an
      adjustable-traction device designed by the authors. METHODS: All patients who
      underwent correction of inverted nipples at the authors' hospital from April 2003
      to March 2014 were retrospectively evaluated. Patients were divided into 2 groups
      according to the correction technique. In group A, 41 nipples in 25 patients
      underwent traditional (conventional) surgical correction. In group B, 74 nipples
      in 40 patients underwent continuous traction using our traction device for 2 to 4
      months. All patients were followed up for 6 to 12 months postoperatively (group
      A) or after finish the course of therapy (group B). Complications and patient
      satisfaction were compared between the groups. RESULTS: No infection occurred in
      either group. In group A, 9 patients were dissatisfied, and a severe complication
      occurred in 1 nipple. In group B, all inverted nipples were corrected, and nipple
      inversion recurred in 2 patients; repeat traction produced a good outcome. Group
      B had fewer complications and higher patient satisfaction than group A.
      CONCLUSIONS: This adjustable continuous-traction technique provided better
      correction of inverted nipples with fewer complications and higher patient
      satisfaction than did traditional surgical correction. This safe, simple,
      effective, minimally invasive technique is suitable for correction of various
      types of inverted nipples.

PMID- 25954843
TI  - The Effect of Polydeoxyribonucleotide on Ischemic Rat Skin Flap Survival.
AB  - Polydeoxyribonucleotide (PDRN) has multiple vascular actions such as angiogenesis
      and production of a vascular endothelial growth factor (VEGF) through the
      adenosine A2 receptor stimulation. We applied PDRN on the ischemic flap of rat
      back and investigated whether it enhances the skin flap survival. A total of 28
      Sprague-Dawley rats were divided into 3 groups, namely, PDRN group, control group
      1 (no treatment), and group 2 (phosphate-buffered saline injection). On the
      distally based flap of 3 * 9 cm in size, it was subdermally injected with PDRN or
      phosphate-buffered saline, which were administered 48 hours prior and immediately
      after flap elevation. The PDRN group was daily maintained by intraperitoneal
      administration of PDRN from the postoperative 1st day to 10th day. The mean
      survival rates of flap in PDRN group [79.5% (6.3%)] are significantly larger than
      control groups [1, 53.0% (6.9%); 2, 51.7% (6.7%)]. Serial measurements of blood
      perfusion also showed that the blood flux was significantly increased in almost
      part of the flap on the 10 days after PDRN injection. The number of CD31
      positively stained vessels and expression of VEGF protein were significantly
      higher in the PDRN group. We propose that administration of PDRN into the
      ischemic skin flaps increased blood flux to the flap, VEGF expression, and number
      of capillaries, thereby improving the rat skin flap survival. 

PMID- 25954844
TI  - Perioperative Arnica montana for Reduction of Ecchymosis in Rhinoplasty Surgery.
AB  - BACKGROUND: Studies of homeopathic therapies to decrease postrhinoplasty
      ecchymosis have previously used subjective measurements, limiting their clinical
      significance. Recently, Arnica montana was shown to decrease postoperative
      ecchymosis after rhytidectomy, using an objective measuring tool. We believe that
      oral A. montana, given perioperatively, can be objectively shown to reduce extent
      and intensity of postoperative ecchymosis in rhinoplasty surgery. METHODS:
      Subjects scheduled for rhinoplasty surgery with nasal bone osteotomies by a
      single surgeon were prospectively randomized to receive either oral perioperative
      A. montana (Alpine Pharmaceuticals, San Rafael, Calif) or placebo in a double
      blinded fashion. Ecchymosis was measured in digital "three-quarter"-view
      photographs at 3 postoperative time points. Each bruise was outlined with Adobe
      Photoshop (Adobe Systems Incorporated, San Jose, Calif), and the extent was
      scaled to a standardized reference card. Cyan, magenta, yellow, black, and
      luminosity were analyzed in the bruised and control areas to calculate change in
      intensity. P value of <0.1 was set as a meaningful difference with statistical
      significance. RESULTS: Compared with 13 subjects receiving placebo, 9 taking A.
      montana had 16.2%, 32.9%, and 20.4% less extent on postoperative days 2/3, 7, and
      9/10, a statistically significant difference on day 7 (P = 0.097). Color change
      initially showed 13.1% increase in intensity with A. montana but 10.9% and 36.3%
      decreases on days 7 and 9/10, a statistically significant difference on day 9/10
      (P = 0.074). One subject experienced mild itching and rash with the study drug
      that resolved during the study period. CONCLUSIONS: Arnica montana seems to
      accelerate postoperative healing, with quicker resolution of the extent and the
      intensity of ecchymosis after osteotomies in rhinoplasty surgery, which may
      dramatically affect patient satisfaction.

PMID- 25954845
TI  - Aggressive Digital Papillary Adenocarcinoma: Case Report of a Positive Sentinel
      Lymph Node and Discussion of Utility of Sentinel Lymph Node Biopsy.
AB  - Aggressive digital papillary adenocarcinoma (ADPA) is an uncommon eccrine sweat
      gland tumor of the distal extremities that is associated with a high rate of
      local recurrence and distant metastasis. Current opinion suggests that sentinel
      lymph node evaluation should be done for high-risk tumors where lymph node spread
      is a concern. Despite documented spread to regional lymph nodes, information on
      sentinel lymph node status in ADPA is reported infrequently, with only 1
      documented case of positive findings. We report on a case of ADPA of the right
      long finger where sentinel lymph node biopsy was done and positive for metastases
      in the axilla, resulting in a subsequent completion lymphadenectomy. To determine
      the benefit of sentinel lymph node biopsy in ADPA, there is a need for more cases
      of sentinel lymph node evaluation along with data on local recurrence and distant
      metastasis in those with positive and negative findings. 

PMID- 25954846
TI  - The Flap Sandwich Technique for a Safe and Aesthetic Skull Base Reconstruction.
AB  - For safe and reliable skull base reconstruction combined with repair of cranial
      bone defects, we introduce the flap sandwich technique in this study. A titanium
      mesh is often used to repair structural cranial bone defects because it has less
      donor site morbidity and is easy to handle. However, titanium mesh has
      disadvantages of exposure and infection postoperatively. To improve surgical
      outcomes, we applied the flap sandwich technique to 3 cases of skull base
      reconstruction combined with cranial bone defect repair. Two anterior skull base
      defects and 1 middle skull base defect were included in this study. The subjects
      were all women, aged 30, 58, and 62 years. One patient had former multiple
      craniotomies and another patient had preoperative radiotherapy. The flap sandwich
      technique involves structural cranial bone reconstruction with a titanium mesh
      and soft tissue reconstruction with a chimeric anterolateral thigh free flap.
      First, the dead space between the repaired dura and the titanium mesh is filled
      with vastus lateralis muscle, and then structural reconstruction is performed
      with a titanium mesh. Finally, the titanium mesh is totally covered with the
      adiposal flap of the anterolateral thigh free flap. The muscle flap protects the
      dead space from infection, and the adiposal flap covers the titanium mesh to
      reduce mechanical stress on the covered skin and thus prevent the exposure of the
      titanium mesh through the scalp. By applying this technique, there was no
      intracranial infection or titanium mesh exposure in these 3 cases
      postoperatively, even though 2 patients had postoperative radiotherapy.
      Additionally, the adiposal flap could provide a soft and natural contour to the
      scalp and forehead region, and this gives patients a better facial appearance
      even though they have had skull base surgery. 

PMID- 25954847
TI  - Longitudinal Ultrasound Study of Breast Implant Rupture Over a Six-Year Interval.
AB  - BACKGROUND: Silicone gel-filled implants as opposed to saline-filled breast
      implants are the most commonly used breast implants in Europe, and this has
      recently also become the case in the United States. Modern implants have a
      multiple layer silicone shell and high to very high levels of cohesive silicone
      gel inside. Although breast magnetic resonance imaging is at present considered
      the gold standard imaging method for breast implant rupture detection, breast
      ultrasound (US) imaging is still the first-step investigation in Europe. The aim
      of this study was to verify whether or not the stepladder sign at US is still
      associated to intracapsular rupture among the last generation silicone breast
      implant. MATERIALS AND METHODS: In this study, 156 patients presenting for breast
      augmentation, mastopexy with implants and breast reconstruction for a total
      number of 303 breast implants inserted were enrolled. A preoperative breast
      ultrasonography was performed, and patients underwent a routine US scan every 6
      months for 24 months to evaluate the implant status. A final US evaluation 6
      years after implantation was also performed. RESULTS: Stepladder signs were seen
      at 6 years in 170 implants (56%) of the examined implants at US scan, and only 2
      implants showed signs of possible rupture because of severe distortion of the
      implant profile with or without external silicone collection. A third ruptured
      implant was detected at magnetic resonance imaging by the presence of breach of
      the shell at the posterior surface of the implant with small external silicon
      collection and was eventually confirmed at surgery. Therefore, the overall
      rupture rate found at the United States at 6 years was about 1% (3 of 303
      implants). According to our findings, the stepladder sign at the United States is
      no longer associated to intracapsular rupture. CONCLUSIONS: Plastic surgeons,
      patients, and financial departments of hospitals would also be delighted to know
      that surgeons should not take patients back to theater for implant explantation
      when aging signs are not associated with a visible breach of the implant shell or
      external silicone collections.

PMID- 25954848
TI  - Complications in Posterior Cranial Vault Distraction.
AB  - BACKGROUND: The use of posterior cranial vault distraction for the treatment of
      elevated intracranial pressure is gaining popularity and is a standard for first
      stage cranial expansion in syndromic craniosynostosis at many institutions.
      However, although the operation is faster and less complex than other cranial
      vault remodeling procedures, it is not without its own unique set of
      complications. METHODS: We surveyed the published literature for case series and
      case control studies on posterior vault distraction. Complication rates and types
      for these series were tabulated and grouped by management. When outcomes were
      unclear, corresponding authors were contacted for clarification and treatment
      plans. RESULTS: Eleven reports were found from a search of all the literature on
      posterior cranial vault distraction with a range of 1 to 22 included patients.
      The average age at surgery was 16.2 +/- 11.8 months. Complication rates ranged
      from 12.5% to 100%, with the average of 30% of patients across all studies. The
      most common complications reported were cerebrospinal fluid leak or dural injury,
      followed by wound infections or device exposures, and device failure. There were
      no reported patient deaths or long-term morbidities. CONCLUSIONS: Posterior
      cranial vault distraction is a relatively safe and effective therapy for the
      treatment of elevated intracranial pressure in the setting of syndromic
      craniosynostosis. The majority of described complications center on the
      interaction of the device with the dura, device extrusion, and infection. Extreme
      care must be used with the placement of these distraction devices and with
      handling of the dura at the osteotomy sites to ensure successful outcomes and
      avoid complications. LEVELS OF EVIDENCE: III.

PMID- 25954849
TI  - Anticoagulation management during multivessel coronary artery bypass grafting: a
      randomized trial comparing individualized heparin management and conventional
      hemostasis management.
AB  - BACKGROUND: Individualized heparin management (IHM) uses heparin dose-response
      curves to improve hemostasis management during cardiac surgery as compared with
      activated clotting time-based methods. OBJECTIVES: IHM was compared with
      conventional hemostasis management (CHM) in a randomized, prospective study (ID
      DRKS00007580). METHODS: One-hundred and twenty patients undergoing multivessel
      coronary artery bypass grafting (CABG) were enrolled. Heparin and protamine
      consumption, blood losses, blood transfusions and administration of hemostatic
      agents were recorded. Time courses of platelet counts and of coagulation
      parameters were determined. Coagulation was analyzed at intensive care unit (ICU)
      arrival by thromboelastometry. RESULTS: IHM patients received significantly lower
      initial heparin doses (289.3IU kg(-1) [interquartile range (IQR) 221.5-376.2 IU
      kg(-1) ] versus 350.5 IU kg(-1) [IQR 346.8-353.7 IU kg(-1) ], P < 0.0001) but
      similar total heparin doses (418.5 IU kg(-1) [IQR 346.9-590.5 IU kg(-1) ] versus
      435.8 IU kg(-1) [IQR 411.7-505.1 IU kg(-1) ]). IHM patients received
      significantly less protamine, resulting in protamine/total heparin ratios of
      0.546 [IQR 0.469-0.597] versus 0.854 [IQR 0.760-0.911] in CHM patients (P <
      0.0001). Activated partial thromboplastin time (50.5 s [IQR 40.0-60.0 s] versus
      37.0 s [IQR 33.0-40.0 s], P < 0.0001), activated clotting time (136 s [IQR 129.0
      150.5 s] versus 126.5 s [IQR 120.3-134.0 s], P = 0.0002) and INTEM clotting times
      (215 s [IQR 192-237] versus 201 s [IQR 191-216 s], P = 0.0397) were significantly
      longer in IHM patients than in CHM patients at ICU arrival, with no difference in
      prothrombin time (P = 0.538). IHM patients lost significantly more blood within
      12 h postoperatively (420 mL [IQR 337.5-605.0 mL] versus 345 mL [IQR 230.0-482.5
      mL], P = 0.0041), and required significantly more hemostatic agents to control
      bleeding. Red blood cell transfusion requirements and time courses of platelet
      counts did not differ between groups. CONCLUSIONS: Multivessel CABG patients did
      not benefit from IHM in comparison with our established protocol based on
      activated clotting time.

PMID- 25954850
TI  - Efficacy and safety of focused ultrasound versus microwave therapy for cervical
      ectopy: a meta-analysis.
AB  - OBJECTIVES: To assess the efficacy and safety of focused ultrasound therapy (FU)
      and microwave therapy (MW) for cervical ectopy (CE). METHODS: We searched PubMed,
      EMbase, the Cochrane Library, Chinese Biomedical Literature Database (CBM),
      Chinese Scientific Journals Database (VIP), China Academic Journals Full-text
      Database (CNKI), and WanFang Data for randomized controlled trials (RCTs)
      comparing FU with MW for women with symptomatic CE from inception to 30 August
      2014. Two review authors (Tang XL and Gao Z) independently screened for eligible
      studies according to the inclusion and exclusion criteria, extracted data and
      assessed risk of bias of included RCTs. Then, meta-analysis was performed using
      the RevMan 5.2 software. Funnel plots were used to evaluate publication bias.
      RESULTS: A total of 33 RCTs with 11,759 participants were included. All studies
      had high risk of bias. The results of meta-analysis indicated that compared to
      MW, FU significantly reduced the risk of vaginal bleeding (RR = 0.09, 95%CI 0.05
      to 0.17, P < 0.00001) and vaginal discharge (RR = 0.10, 95%CI 0.04 to 0.24, P <
      0.00001), increased the cure rate (RR = 1.10, 95%CI 1.05 to 1.15, P < 0.0001) and
      the total effectiveness rate (RR = 1.04, 95%CI 1.02 to 1.06, P = 0.0005), and
      decreased the recurrence rate (RR = 0.13, 95%CI 0.02 to 1.00, P = 0.05); however,
      this last difference was not statistically significant. CONCLUSION: Current
      available evidence suggests that FU is safer and more effective than MW for
      treating CE. However, some limitations will reduce the reliability of our
      results. Further well-designed clinical trials are needed to provide further
      clarification.

PMID- 25954851
TI  - Long term persistence of NS5A inhibitor-resistant hepatitis C virus in patients
      who failed daclatasvir and asunaprevir therapy.
AB  - Although interferon-free antiviral treatment is expected to improve treatment of
      hepatitis C, it is unclear to what extent pre-existing drug-resistant amino acid
      substitutions influence response to therapy. The impact of pre-existing drug
      resistant substitutions on virological response to daclatasvir and asunaprevir
      combination therapy was studied in genotype 1b hepatitis C virus (HCV)-infected
      patients. Thirty-one patients were treated with daclatasvir and asunaprevir for
      24 weeks. Twenty-six patients achieved sustained virological response (SVR),
      three patients experienced viral breakthrough, and two patients relapsed. Direct
      sequencing analysis of HCV showed the existence of daclatasvir-resistant NS5A
      L31M or -Y93H/F variants in nine out of 30 patients (30%) prior to treatment,
      while asunaprevir-resistant NS3-D168 mutations were not detected in any patient.
      All 21 patients with wild-type NS5A-L31 and -Y93 achieved SVR, whereas only four
      out of nine patients (44%) with L31M or Y93F/H substitutions achieved SVR (P =
      0.001). Ultra-deep sequencing analysis showed that treatment failure was
      associated with the emergence of both NS5A-L31/Y93 and NS3-D168 variants. NS5A
      L31/Y93 variants remained at high frequency through post-treatment weeks 103
      through 170, while NS3-D168 variants were replaced by wild-type in all patients.
      In conclusion, pre-existence of NS5A inhibitor-resistant substitutions
      compromised the response to daclatasvir and asunaprevir combination therapy, and
      treatment failure was associated with the emergence of both NS5A-L31/Y93 and NS3
      D168 variants. While asunaprevir-resistant variants that emerged during therapy
      returned to wild-type, daclatasvir-resistant variants tended to persist in the
      absence of the drug.

PMID- 25954852
TI  - Prior high-risk HPV testing and Pap test results for 427 invasive cervical
      cancers in China's largest CAP-certified laboratory.
AB  - BACKGROUND: Cervical cancer and its precursor lesions are caused by a persistent
      high-risk human papillomavirus (hrHPV) infection. hrHPV testing has been reported
      to have higher sensitivity than Papanicolaou (Pap) testing for the detection of
      cervical precursor lesions. However, limited data are available for prior human
      papillomavirus (HPV) testing results for patients later diagnosed with invasive
      cervical cancer, especially in countries lacking a national cervical cancer
      screening program such as China. This study investigated prior hrHPV testing
      results for patients with invasive cervical cancer in China. METHODS: Cases with
      a histologic diagnosis of invasive cervical carcinoma were retrieved from
      Guangzhou KingMed Diagnostics (the largest independent pathology laboratory in
      China); prior hrHPV and Pap test results obtained within the year before the
      cancer diagnosis were recorded. RESULTS: HPV testing was negative in 7.5% of 427
      cases of invasive cervical carcinoma, including squamous cell carcinoma (5%) and
      adenocarcinoma (25%). In 155 cervical cancer cases with prior hrHPV and Pap
      testing, the negative rate for Pap testing was 1.9%, and the negative rate for
      HPV was 9.7%. Furthermore, when only cases of adenocarcinoma (n = 18) were
      examined, both the hrHPV-negative rate and the Pap-negative rate were higher at
      33% and 5.6%, respectively. CONCLUSIONS: These data demonstrate a considerable
      prior hrHPV-negative rate and a lower prior Pap-negative rate in patients with
      invasive cervical carcinoma (especially adenocarcinoma) from a population of
      women without access to an established screening program.

PMID- 25954854
TI  - Solvent effects and driving forces in pillararene inclusion complexes.
AB  - Pillararenes, a recently discovered class of aromatic macrocycles, form inclusion
      complexes with a large number of guest molecules, but not much is known about the
      driving forces of complexation, including the role of the solvent. We have
      measured the binding thermodynamics for a small number of model complexes in
      several solvents and used computational chemistry to rationalize the obtained
      results and identify the driving forces of complexation. Favorable electrostatic
      interactions between the host and guest are obtained when the charge distribution
      in the guest matches the negative electrostatic potential in the cavity of the
      pillararene. Polar guests, however, also interact strongly with polar solvents,
      thereby shifting the complexation equilibrium away from the complex. The shape of
      the solvent molecules is another important factor as some solvents are sterically
      hindered from entering the pillararene cavity. By changing solvent from
      acetonitrile to o-xylene the binding constant in one case increased more than 4
      orders of magnitude. Even electrostatically similar solvents such as o-xylene and
      p-xylene have very different impacts on the binding constants due to their
      different abilities to fit into the cavity. The study illustrates the importance
      of taking into account the interactions between the solvent and the complexing
      species in the investigation and design of molecular host:guest systems. 

PMID- 25954853
TI  - X609, a novel manassantin A derivative, exhibits antitumor activity in MG-63
      human osteosarcoma cells in vitro and in vivo.
AB  - Manassantin A has been well-established as an inhibitor of HIF-1. In the present
      study, a new manasantin A derivative, X609, with decreased stereochemical
      complexity, rendering it amenable to a simplified synthesis scheme, was
      synthesized and was found to increase HIF-1 inhibitory activity. X609 exhibited
      antiproliferative activity in a broad spectrum of tumor cell lines, via HIF-1
      dependent mechanisms. X609 may induce apoptosis in MG-63 cells through activation
      of the mitochondrial pathway. Oral administration of X609 significantly inhibited
      the growth of human osteosarcomas implanted into nude mice. In light of the
      results of the present study, it may be possible to develop X609 for use as a
      novel antitumor agent, which targets human osteosarcoma.

PMID- 25954855
TI  - Paeoniflorin inhibits proliferation and induces apoptosis of human glioma cells
      via microRNA-16 upregulation and matrix metalloproteinase-9 downregulation.
AB  - Paeoniflorin is one of the active ingredients of the commonly used herbal
      medicine derived from Paeonia, which exhibits anticancer properties. MicroRNA-16
      (miR-16) is upregulated in CD133(-) cells, but downregulated in CD133(+) cells
      from glioma tissue. Matrix metalloproteinase-9 (MMP-9) expression in glioma
      tissue samples is significantly higher than that in healthy brain tissue samples.
      Therefore, miR-16 and MMP-9 expression may be associated with glioma
      pathogenesis. In the present study, the effects of paeoniflorin on glioma were
      analyzed. U87 cells were treated with paeoniflorin at 0, 5, 10 and 20 MUMU
      concentrations. The results suggested that paeoniflorin inhibited U87 cell
      proliferation and accelerated cell apoptosis. In the present study paeoniflorin
      treatment increased miR-16 expression and reduced MMP-9 protein expression in U87
      cells. Additionally, the results of the present study suggested that miR-16 may
      regulate MMP-9 expression in miR-16-transfected U87 cells. Furthermore, anti-miR
      16 antibodies were used in order to investigate the apoptotic effects of
      paeoniflorin on U87 cells. The results demonstrated that paeoniflorin inhibits
      proliferation and induces apoptosis of human glial cells, via miR-16 upregulation
      and MMP-9 downregulation.

PMID- 25954856
TI  - Oncostatin M activates STAT3 to promote endometrial cancer invasion and
      angiogenesis.
AB  - Oncostatin M (OSM), a pleiotropic cytokine, can either promote or inhibit the
      growth of tumors derived from specific tissues. However, little is known about
      the activity and expression pattern of OSM in endometrial cancers (ECs). Herein
      we show that expression of OSM in human ECs was significantly higher than that in
      hyperplastic or normal tissues. In EC tissues, high OSM levels were positively
      correlated with tumor stage, histological grade, myometrial invasion, and lymph
      node metastasis. Additionally, we demonstrated that recombinant human OSM (rhOSM)
      promoted tumor angiogenesis in EC cell lines by activating STAT3 (signal
      transducer and activator of transcription 3) and enhanced both cell migration and
      cell invasion. rhOSM did not, however, influence the proliferation of EC cells in
      vitro. In contrast, in our in vivo xenograft model, overexpression of rhOSM
      promoted cell proliferation, tumor growth, and angiogenesis in nude mice.
      Collectively, these experiments suggest that OSM may be a tumor promoter that
      encourages EC progression. OSM may thus serve as a potential target of
      antiangiogenic therapy for endometrial cancer.

PMID- 25954857
TI  - Neurofeedback in the workplace: from neurorehabilitation hope to neuroleadership
      hype?
AB  - Brain-computer interface neurofeedback has rapidly become an engaging topic for
      occupational research at large. Notwithstanding some criticism, research and
      practice have begun converging on the efficacy of brain-computer interface
      neurofeedback as a part of holistic interventions in rehabilitation. Yet, its use
      in vocational contexts has recently blossomed into wider attributes, beyond
      rehabilitation practice per se, additionally targeting performance enhancements
      and leadership interventions in healthy individuals. By exploring this emerging
      scenario, this paper aims to provide an interdisciplinary forum of analysis on
      the deriving implications for rehabilitation professionals, signaling how these
      may invite both possible threats for the field and opportunities to engage in
      novel translational partnerships. 

PMID- 25954858
TI  - Cross-cultural adaptation and psychometric properties of an Arabic version of the
      Shoulder Pain and Disability Index.
AB  - The aim of the present study was to translate, culturally adapt, and validate the
      Arabic version of the shoulder Pain and Disability Index (SPADI). This was an
      observational reliability and validity study. We recruited 64 patients with
      shoulder pain and dysfunction with a wide variety of diagnoses. Patients
      completed the following questionnaires: Arabic SPADI, Quick Disability of the
      arm, shoulder and hand (Quick DASH), and the numerical rating scale (NRS) for
      pain. The active shoulder range of motion (ROM) was also assessed. Internal
      consistency was tested using Cronbach alpha. Reproducibility was assessed by
      asking the patients to complete another SPADI questionnaire 2 days after the
      first. Validity was assessed by calculating the Pearson correlation coefficient
      between the SPADI and the Quick DASH, NRS, and active shoulder ROM. The Cronbach
      alpha values for the pain score (0.96), disability score (0.98), and total score
      (0.98) of Arabic SPADI were all high. Similarly, the intraclass correlation
      coefficient (ICC) values for the pain, disability, and total score (ICC, 0.87,
      0.96, and 0.95, respectively) of Arabic SPADI were all high. With respect to
      validity, there was a moderate to strong correlation between the Arabic SPADI and
      the Quick DASH, NRS, and active shoulder ROM. The translated version of SPADI in
      the Arabic language showed excellent internal consistency and test-retest
      reliability. Validity was shown by substantial correlations between SPADI and
      Quick DASH, NRS, and active shoulder ROM. The Arabic SPADI is recommended for the
      evaluation of patients with shoulder dysfunction. 

PMID- 25954859
TI  - Synthesis of the Layered Quaternary Uranium-Containing Oxide Cs2Mn3U6O22 and
      Characterization of its Magnetic Properties.
AB  - A layered quaternary uranium-containing oxide, Cs2Mn3U6O22, was crystallized from
      a cesium chloride flux. The crystal structure was determined to consist of alpha
      U3O8 topological layers that are separated by alternating cesium and manganese
      layers. This ordered arrangement creates a separation between manganese layers of
      13 A, leading to complex low-dimensional magnetic properties. The compound
      crystallizes in a new structure type in the monoclinic space group, C2/m, with a
      = 6.8730(10) A, b = 11.7717(17) A, c = 13.374(2) A, and beta = 99.673(5) degrees
      . The magnetic properties were measured and analyzed by first-principles density
      functional theory calculations. 

PMID- 25954860
TI  - Low expression of phosphatase and tensin homolog in clear-cell renal cell
      carcinoma contributes to chemoresistance through activating the Akt/HDM2
      signaling pathway.
AB  - Clear-cell renal cell carcinoma (CCRCC) is the most frequent primary malignancy
      in the adult kidney. Most patients with advanced CCRCC have poor prognosis as
      CCRCC remains resistant to chemotherapy. The present study explored the possible
      mechanism underlying CCRCC resistance to chemotherapy and found that loss of PTEN
      in CCRCC may be involved. Knockdown of PTEN in the CCRCC cell line ACHN blocked
      etoposide-induced apoptosis and etoposide-impaired cell proliferation was also
      inhibited. It has been demonstrated that most chemotherapy drugs exert their anti
      cancer effects via p53-mediated apoptosis, and in accordance, with this, the
      present study showed that treatment with etoposide significantly increased p53
      levels. Silencing of PTEN in ACHN inhibited the Akt/HDM2 signaling cascade and
      depressed p53 expression, and the interaction between HDM2 and p53 was also
      enhanced. This was further verified in CCRCC tissue specimens from patients The
      results of the present study suggested that loss of PTEN, which deactivated
      Akt/HDM2 signaling followed by degradation of p53, may contribute to the
      development of etoposide resistance in CCRCC.

PMID- 25954861
TI  - Regulation of a cerium(IV)-driven O2 evolution reaction using composites of
      liposome and lipophilic ruthenium complexes.
AB  - A composite containing a liposome and a lipophilic ruthenium complex was
      synthesized to regulate an O2 evolution reaction using cerium(IV) ammonium
      nitrate as an oxidizing reagent. We found that the surrounding environment of the
      reaction centre is an important factor for controlling the O2 evolution catalytic
      reaction. We successfully regulated the reaction activity using the linker length
      of the lipophilic ligand and using the head groups of the phospholipid component.

PMID- 25954862
TI  - Potential effect of ultrasound on carbohydrates.
AB  - The use of ultrasound has emerged as one of the most useful alternative energy
      sources for the synthesis of carbohydrate-derived biologically and
      pharmaceutically potential compounds. Spectacular advances have been made in the
      field of sonication-assisted organic reactions, which are known for producing
      superior yields, enhanced reactivity of the reactant, improved stereoselectivity,
      and shortened reaction times. Orthogonal protection-deprotection reactions and/or
      modification and manipulation of functional groups in carbohydrates are common
      synthetic steps in carbohydrate chemistry. These reaction steps can be driven by
      the ultrasonic energy generated by acoustic cavitation via the formation and
      subsequent collapse of ultrasound-induced bubbles. The ultrasound-assisted
      synthesis of differently functionalised monosaccharides is useful in a wide
      variety of applications of carbohydrate chemistry such as the glycosylation of
      oligosaccharides, one pot domino reactions, thioglycoside syntheses,
      azidoglycoside syntheses, 1,3-dipolar cycloaddition reactions, and syntheses of
      natural products. This review article covers ultrasound-mediated reactions on
      carbohydrates that have been described in the literature since 2000. 

PMID- 25954863
TI  - Efficient regioselective O3-monodesilylation by hydrochloric acid in
      cyclodextrins.
AB  - An efficient O3-monodesilylation method has been developed for the derivatization
      of per-3-O-silylated cyclodextrin (CD) derivatives. Using hydrochloric acid as a
      reagent, the O3-monodesilylation was found to be regioselective, mild, practical
      and general as it can be applied to all alpha-, beta- and gamma-CDs. The
      advantage of the methodology is that the acid-catalyzed O3-desilylation can be
      carried out in a stepwise manner so that different types of functional groups can
      be introduced to a CD molecule at different stage of the O3-desilylations. This
      makes the current methodology flexible and versatile. This current methodology
      constitutes one of the few methodologies available for the regioselective
      modification of CDs at the secondary face. 

PMID- 25954864
TI  - T cells have a light touch.

PMID- 25954865
TI  - Anomalous diffusion inspires anatomical insights.

PMID- 25954866
TI  - Forcing filament fragmentation with cofilin.

PMID- 25954867
TI  - Of rafts and lipid chain lengths.

PMID- 25954868
TI  - Multidomain Assembler (MDA) Generates Models of Large Multidomain Proteins.
AB  - Homology modeling predicts protein structures using known structures of related
      proteins as templates. We developed MULTIDOMAIN ASSEMBLER (MDA) to address the
      special problems that arise when modeling proteins with large numbers of domains,
      such as fibronectin with 30 domains, as well as cases with hundreds of templates.
      These problems include how to spatially arrange nonoverlapping template
      structures, and how to get the best template coverage when some sequence regions
      have hundreds of available structures while other regions have a few distant
      homologs. MDA automates the tasks of template searching, visualization, and
      selection followed by multidomain model generation, and is part of the widely
      used molecular graphics package UCSF CHIMERA (University of California, San
      Francisco). We demonstrate applications and discuss MDA's benefits and
      limitations. 

PMID- 25954869
TI  - A primer on Bayesian inference for biophysical systems.
AB  - Bayesian inference is a powerful statistical paradigm that has gained popularity
      in many fields of science, but adoption has been somewhat slower in biophysics.
      Here, I provide an accessible tutorial on the use of Bayesian methods by focusing
      on example applications that will be familiar to biophysicists. I first discuss
      the goals of Bayesian inference and show simple examples of posterior inference
      using conjugate priors. I then describe Markov chain Monte Carlo sampling and, in
      particular, discuss Gibbs sampling and Metropolis random walk algorithms with
      reference to detailed examples. These Bayesian methods (with the aid of Markov
      chain Monte Carlo sampling) provide a generalizable way of rigorously addressing
      parameter inference and identifiability for arbitrarily complicated models. 

PMID- 25954870
TI  - Surfing along Filopodia: A Particle Transport Revealed by Molecular-Scale
      Fluctuation Analyses.
AB  - Filopodia perform cellular functions such as environmental sensing or cell
      motility, but they also grab for particles and withdraw them leading to an
      increased efficiency of phagocytic uptake. Remarkably, withdrawal of micron-sized
      particles is also possible without noticeable movements of the filopodia. Here,
      we demonstrate that polystyrene beads connected by optical tweezers to the ends
      of adherent filopodia of J774 macrophages, are transported discontinuously toward
      the cell body. After a typical resting time of 1-2 min, the cargo is moved with
      alternating velocities, force constants, and friction constants along the surface
      of the filopodia. This surfing-like behavior along the filopodium is recorded by
      feedback-controlled interferometric three-dimensional tracking of the bead
      motions at 10-100 kHz. We measured transport velocities of up to 120 nm/s and
      transport forces of ~ 70 pN. Small changes in position, fluctuation width, and
      temporal correlation, which are invisible in conventional microscopy, indicate
      molecular reorganization of transport-relevant proteins in different phases of
      the entire transport process. A detailed analysis implicates a controlled
      particle transport with fingerprints of a nanoscale unbinding/binding behavior.
      The manipulation and analysis methods presented in our study may also be helpful
      in other fields of cellular biophysics.

PMID- 25954871
TI  - Viscoelastic transient of confined red blood cells.
AB  - The unique ability of a red blood cell to flow through extremely small
      microcapillaries depends on the viscoelastic properties of its membrane. Here, we
      study in vitro the response time upon flow startup exhibited by red blood cells
      confined into microchannels. We show that the characteristic transient time
      depends on the imposed flow strength, and that such a dependence gives access to
      both the effective viscosity and the elastic modulus controlling the temporal
      response of red cells. A simple theoretical analysis of our experimental data,
      validated by numerical simulations, further allows us to compute an estimate for
      the two-dimensional membrane viscosity of red blood cells, eta(mem)(2D) ~ 10(-7)
      N ? s ? m(-1). By comparing our results with those from previous studies, we
      discuss and clarify the origin of the discrepancies found in the literature
      regarding the determination of eta(mem)(2D), and reconcile seemingly conflicting
      conclusions from previous works.

PMID- 25954873
TI  - Raman spectral dynamics of single cells in the early stages of growth factor
      stimulation.
AB  - Cell fates change dynamically in response to various extracellular signals,
      including growth factors that stimulate differentiation and proliferation. The
      processes underlying cell-fate decisions are complex and often include large cell
      to-cell variations, even within a clonal population in the same environment. To
      understand the origins of these cell-to-cell variations, we must detect the
      internal dynamics of single cells that reflect their changing chemical milieu. In
      this study, we used the Raman spectra of single cells to trace their internal
      dynamics during the early stages of growth factor stimulation. This method allows
      nondestructive and inclusive time-series analyses of chemical compositions of the
      same single cells. Applying a Gaussian mixture model to the major principal
      components of the single-cell Raman spectra, we detected the dynamics of the
      chemical states in MCF-7 cancer-derived cells in the absence and presence of
      differentiation and proliferation factors. The dynamics displayed characteristic
      variations according to the functions of the growth factors. In the
      differentiation pathway, the chemical composition changed directionally between
      multiple states, including both reversible and irreversible state transitions. In
      contrast, in the proliferation pathway, the chemical composition was homogenized
      into a single state. The differentiation factor also stimulated fluctuations in
      the chemical composition, whereas the proliferation factor did not. 

PMID- 25954872
TI  - CNS cell distribution and axon orientation determine local spinal cord mechanical
      properties.
AB  - Mechanical signaling plays an important role in cell physiology and pathology.
      Many cell types, including neurons and glial cells, respond to the mechanical
      properties of their environment. Yet, for spinal cord tissue, data on tissue
      stiffness are sparse. To investigate the regional and direction-dependent
      mechanical properties of spinal cord tissue at a spatial resolution relevant to
      individual cells, we conducted atomic force microscopy (AFM) indentation and
      tensile measurements on acutely isolated mouse spinal cord tissue sectioned along
      the three major anatomical planes, and correlated local mechanical properties
      with the underlying cellular structures. Stiffness maps revealed that gray matter
      is significantly stiffer than white matter irrespective of directionality
      (transverse, coronal, and sagittal planes) and force direction (compression or
      tension) (K(g) = ~ 130 P(a) vs. K(w) = ~ 70 Pa); both matters stiffened with
      increasing strain. When all data were pooled for each plane, gray matter behaved
      like an isotropic material under compression; however, subregions of the gray
      matter were rather heterogeneous and anisotropic. For example, in sagittal
      sections the dorsal horn was significantly stiffer than the ventral horn. In
      contrast, white matter behaved transversely isotropic, with the elastic stiffness
      along the craniocaudal (i.e., longitudinal) axis being lower than perpendicular
      to it. The stiffness distributions we found under compression strongly correlated
      with the orientation of axons, the areas of cell nuclei, and cellular in plane
      proximity. Based on these morphological parameters, we developed a
      phenomenological model to estimate local mechanical properties of central nervous
      system (CNS) tissue. Our study may thus ultimately help predicting local tissue
      stiffness, and hence cell behavior in response to mechanical signaling under
      physiological and pathological conditions, purely based on histological data.

PMID- 25954874
TI  - Covert Changes in CaMKII Holoenzyme Structure Identified for Activation and
      Subsequent Interactions.
AB  - Between 8 to 14 calcium-calmodulin (Ca(2+)/CaM) dependent protein kinase-II
      (CaMKII) subunits form a complex that modulates synaptic activity. In living
      cells, the autoinhibited holoenzyme is organized as catalytic-domain pairs
      distributed around a central oligomerization-domain core. The functional
      significance of catalytic-domain pairing is not known. In a provocative model,
      catalytic-domain pairing was hypothesized to prevent ATP access to catalytic
      sites. If correct, kinase-activity would require catalytic-domain pair
      separation. Simultaneous homo-FRET and fluorescence correlation spectroscopy was
      used to detect structural changes correlated with kinase activation under
      physiological conditions. Saturating Ca(2+)/CaM triggered Threonine-286
      autophosphorylation and a large increase in CaMKII holoenzyme hydrodynamic volume
      without any appreciable change in catalytic-domain pair proximity or subunit
      stoichiometry. An alternative hypothesis is that two appropriately positioned
      Threonine-286 interaction-sites (T-sites), each located on the catalytic-domain
      of a pair, are required for holoenzyme interactions with target proteins.
      Addition of a T-site ligand, in the presence of Ca(2+)/CaM, elicited a large
      decrease in catalytic-domain homo-FRET, which was blocked by mutating the T-site
      (I205K). Apparently catalytic-domain pairing is altered to allow T-site
      interactions. 

PMID- 25954875
TI  - PKCalpha-Mediated Signals Regulate the Motile Responses of Cochlear Outer Hair
      Cells.
AB  - There is strong evidence that changes in the actin/spectrin-based cortical
      cytoskeleton of outer hair cells (OHCs) regulate their motile responses as well
      as cochlear amplification, the process that optimizes the sensitivity and
      frequency selectivity of the mammalian inner ear. Since a RhoA/protein kinase C
      (PKC)-mediated pathway is known to inhibit the actin-spectrin interaction in
      other cell models, we decided to investigate whether this signaling cascade could
      also participate in the regulation of OHC motility. We used high-speed video
      microscopy and confocal microscopy to explore the effects of pharmacological
      activation of PKCalpha, PKCbetaI, PKCbetaII, PKCdelta, PKCepsilon, and PKCzeta
      with lysophosphatidic acid (LPA) and their inhibition with bisindolylmaleimide I,
      as well as inhibition of RhoA and Rho-associated protein kinase (ROCK) with C3
      and Y-27632, respectively. Motile responses were induced in isolated guinea pig
      OHCs by stimulation with an 8 V/cm external alternating electrical field as 50 Hz
      bursts of square wave pulses (100 ms on/off). We found that LPA increased
      expression of PKCalpha and PKCzeta only, with PKCalpha, but not PKCzeta,
      phosphorylating the cytoskeletal protein adducin of both Ser-726 and Thr-445.
      Interestingly, however, inhibition of PKCalpha reduced adducin phosphorylation
      only at Ser-726. We also determined that LPA activation of a PKCalpha-mediated
      signaling pathway simultaneously enhanced OHC electromotile amplitude and cell
      shortening, and facilitated RhoA/ROCK/LIMK1-mediated cofilin phosphorylation.
      Altogether, our results suggest that PKCalpha-mediated signals, probably via
      adducin-mediated inhibition of actin-spectrin binding and cofilin-mediated
      depolymerization of actin filaments, play an essential role in the homeostatic
      regulation of OHC motility and cochlear amplification.

PMID- 25954876
TI  - Human Primary Immune Cells Exhibit Distinct Mechanical Properties that Are
      Modified by Inflammation.
AB  - T lymphocytes are key modulators of the immune response. Their activation
      requires cell-cell interaction with different myeloid cell populations of the
      immune system called antigen-presenting cells (APCs). Although T lymphocytes have
      recently been shown to respond to mechanical cues, in particular to the stiffness
      of their environment, little is known about the rigidity of APCs. In this study,
      single-cell microplate assays were performed to measure the viscoelastic moduli
      of different human myeloid primary APCs, i.e., monocytes (Ms, storage modulus of
      520 +90/-80 Pa), dendritic cells (DCs, 440 +110/-90 Pa), and macrophages (MPHs,
      900 +110/-100 Pa). Inflammatory conditions modulated these properties, with
      storage moduli ranging from 190 Pa to 1450 Pa. The effect of inflammation on the
      mechanical properties was independent of the induction of expression of commonly
      used APC maturation markers, making myeloid APC rigidity an additional feature of
      inflammation. In addition, the rigidity of human T lymphocytes was lower than
      that of all myeloid cells tested and among the lowest reported (Young's modulus
      of 85 +/- 5 Pa). Finally, the viscoelastic properties of myeloid cells were
      dependent on both their filamentous actin content and myosin IIA activity,
      although the relative contribution of these parameters varied within cell types.
      These results indicate that T lymphocytes face different cell rigidities when
      interacting with myeloid APCs in vivo and that this mechanical landscape changes
      under inflammation. 

PMID- 25954877
TI  - Polycystin-2 (TRPP2) Regulation by Ca(2+) Is Effected and Diversified by Actin
      Binding Proteins.
AB  - Calcium regulation of Ca(2+)-permeable ion channels is an important mechanism in
      the control of cell function. Polycystin-2 (PC2, TRPP2), a member of the
      transient receptor potential superfamily, is a nonselective cation channel with
      Ca(2+) permeability. The molecular mechanisms associated with PC2 regulation by
      Ca(2+) remain ill-defined. We recently demonstrated that PC2 from human
      syncytiotrophoblast (PC2hst) but not the in vitro translated protein (PC2(iv)),
      functionally responds to changes in intracellular (cis) Ca(2+). In this study we
      determined the regulatory effect(s) of Ca(2+)-sensitive and -insensitive actin
      binding proteins (ABPs) on PC2(iv) channel function in a lipid bilayer system.
      The actin-bundling protein alpha-actinin increased PC2(iv) channel function in
      the presence of cis Ca(2+), although instead was inhibitory in its absence.
      Conversely, filamin that shares actin-binding domains with alpha-actinin had a
      strong inhibitory effect on PC2(iv) channel function in the presence, but no
      effect in the absence of cis Ca(2+). Gelsolin stimulated PC2(iv) channel function
      in the presence, but not the absence of cis Ca(2+). In contrast, profilin that
      shares actin-binding domains with gelsolin, significantly increased PC2(iv)
      channel function both in the presence and absence of Ca(2+). The distinct
      effect(s) of the ABPs on PC2(iv) channel function demonstrate that Ca(2+)
      regulation of PC2 is actually mediated by direct interaction(s) with structural
      elements of the actin cytoskeleton. These data indicate that specific ABP-PC2
      complexes would confer distinct Ca(2+)-sensitive properties to the channel
      providing functional diversity to the cytoskeletal control of transient receptor
      potential channel regulation.

PMID- 25954878
TI  - MPP1 as a Factor Regulating Phase Separation in Giant Plasma Membrane-Derived
      Vesicles.
AB  - The existence of membrane-rafts helps to conceptually understand the
      spatiotemporal organization of membrane-associated events (signaling, fusion,
      fission, etc.). However, as rafts themselves are nanoscopic, dynamic, and
      transient assemblies, they cannot be directly observed in a metabolizing cell by
      traditional microscopy. The observation of phase separation in giant plasma
      membrane-derived vesicles from live cells is a powerful tool for studying lateral
      heterogeneity in eukaryotic cell membranes, specifically in the context of
      membrane rafts. Microscopic phase separation is detectable by fluorescent
      labeling, followed by cooling of the membranes below their miscibility phase
      transition temperature. It remains unclear, however, if this lipid-driven process
      is tuneable in any way by interactions with proteins. Here, we demonstrate that
      MPP1, a member of the MAGUK family, can modulate membrane properties such as the
      fluidity and phase separation capability of giant plasma membrane-derived
      vesicles. Our data suggest that physicochemical domain properties of the membrane
      can be modulated, without major changes in lipid composition, through proteins
      such as MPP1. 

PMID- 25954879
TI  - Ordered raft domains induced by outer leaflet sphingomyelin in cholesterol-rich
      asymmetric vesicles.
AB  - Sphingolipid- and cholesterol-rich liquid-ordered (Lo) lipid domains (rafts) are
      thought to be important organizing elements in eukaryotic plasma membranes. How
      they form in the sphingolipid-poor cytosolic (inner) membrane leaflet is unclear.
      Here, we characterize how outer-leaflet Lo domains induce inner-leaflet-ordered
      domains, i.e., interleaflet coupling. Asymmetric vesicles studied contained
      physiologically relevant cholesterol levels (~ 37 mol %), a mixture of SM
      (sphingomyelin) and DOPC (dioleoylphosphatidylcholine) in their outer leaflets,
      and DOPC in their inner leaflets. Lo domains were observed in both leaflets, and
      were in register, indicative of coupling between SM-rich outer-leaflet-ordered
      domains and inner-leaflet-ordered domains. For asymmetric vesicles with outer
      leaflet egg SM or milk SM, a fluorescent lipid with unsaturated acyl chains (NBD
      DOPE) was depleted in both the outer- and inner-leaflet-ordered domains. This
      suggests the inner-leaflet-ordered domains were depleted in unsaturated lipid
      (i.e., DOPC) and thus rich in cholesterol. For asymmetric vesicles containing egg
      SM, outer-leaflet Lo domains were also depleted in a saturated fluorescent lipid
      (NBD-DPPE), while inner-leaflet Lo domains were not. This indicates that inner-
      and outer-leaflet Lo domains can have significantly different physical
      properties. In contrast, in asymmetric vesicles containing outer-leaflet milk SM,
      which has long acyl chains capable of interdigitating into the inner leaflet,
      both outer- and inner-leaflet Lo domains were depleted, to a similar extent, in
      NBD-DPPE. This is indicative of interdigitation-enhanced coupling resulting in
      inner- and outer-leaflet Lo domains with similar physical properties.

PMID- 25954880
TI  - Characterization of PROPPIN-Phosphoinositide Binding and Role of Loop 6CD in
      PROPPIN-Membrane Binding.
AB  - PROPPINs (beta-propellers that bind polyphosphoinositides) are a family of
      PtdIns3P- and PtdIns(3,5)P2-binding proteins that play an important role in
      autophagy. We analyzed PROPPIN-membrane binding through isothermal titration
      calorimetry (ITC), stopped-flow measurements, mutagenesis studies, and molecular
      dynamics (MD) simulations. ITC measurements showed that the yeast PROPPIN family
      members Atg18, Atg21, and Hsv2 bind PtdIns3P and PtdIns(3,5)P2 with high
      affinities in the nanomolar to low-micromolar range and have two phosphoinositide
      (PIP)-binding sites. Single PIP-binding site mutants have a 15- to 30-fold
      reduced affinity, which explains the requirement of two PIP-binding sites in
      PROPPINs. Hsv2 bound small unilamellar vesicles with a higher affinity than it
      bound large unilamellar vesicles in stopped-flow measurements. Thus, we conclude
      that PROPPIN membrane binding is curvature dependent. MD simulations revealed
      that loop 6CD is an anchor for membrane binding, as it is the region of the
      protein that inserts most deeply into the lipid bilayer. Mutagenesis studies
      showed that both hydrophobic and electrostatic interactions are required for
      membrane insertion of loop 6CD. We propose a model for PROPPIN-membrane binding
      in which PROPPINs are initially targeted to membranes through nonspecific
      electrostatic interactions and are then retained at the membrane through PIP
      binding. 

PMID- 25954881
TI  - Single Cell Wall Nonlinear Mechanics Revealed by a Multiscale Analysis of AFM
      Force-Indentation Curves.
AB  - Individual plant cells are rather complex mechanical objects. Despite the fact
      that their wall mechanical strength may be weakened by comparison with their
      original tissue template, they nevertheless retain some generic properties of the
      mother tissue, namely the viscoelasticity and the shape of their walls, which are
      driven by their internal hydrostatic turgor pressure. This viscoelastic behavior,
      which affects the power-law response of these cells when indented by an atomic
      force cantilever with a pyramidal tip, is also very sensitive to the culture
      media. To our knowledge, we develop here an original analyzing method, based on a
      multiscale decomposition of force-indentation curves, that reveals and quantifies
      for the first time the nonlinearity of the mechanical response of living single
      plant cells upon mechanical deformation. Further comparing the nonlinear strain
      responses of these isolated cells in three different media, we reveal an
      alteration of their linear bending elastic regime in both hyper- and hypotonic
      conditions.

PMID- 25954882
TI  - Kinesin-1 motors can circumvent permanent roadblocks by side-shifting to
      neighboring protofilaments.
AB  - Obstacles on the surface of microtubules can lead to defective cargo transport,
      proposed to play a role in neurological diseases such as Alzheimer's. However,
      little is known about how motor proteins, which follow individual microtubule
      protofilaments (such as kinesin-1), deal with obstacles on the molecular level.
      Here, we used rigor-binding mutants of kinesin-1 as roadblocks to permanently
      obstruct individual microtubule binding sites and studied the movement of
      individual kinesin-1 motors by single-molecule fluorescence and dark-field
      scattering microscopy in vitro. In the presence of roadblocks, kinesin-1 often
      stopped for ~ 0.4 s before either detaching or continuing to move, whereby the
      latter circumvention events occurred in >30% after a stopping event.
      Consequently, and in agreement with numerical simulations, the mean velocity,
      mean run length, and mean dwell time of the kinesin-1 motors decreased upon
      increasing the roadblock density. Tracking individual kinesin-1 motors labeled by
      40 nm gold particles with 6 nm spatial and 1 ms temporal precision revealed that
      ~ 70% of the circumvention events were associated with significant transverse
      shifts perpendicular to the axis of the microtubule. These side-shifts, which
      occurred with equal likelihood to the left and right, were accompanied by a range
      of longitudinal shifts suggesting that roadblock circumvention involves the
      unbinding and rebinding of the motors. Thus, processive motors, which commonly
      follow individual protofilaments in the absence of obstacles, appear to possess
      intrinsic circumvention mechanisms. These mechanisms were potentially optimized
      by evolution for the motor's specific intracellular tasks and environments.

PMID- 25954883
TI  - Coarse-Grained Model of SNARE-Mediated Docking.
AB  - Synaptic transmission requires that vesicles filled with neurotransmitter
      molecules be docked to the plasma membrane by the SNARE protein complex. The
      SNARE complex applies attractive forces to overcome the long-range repulsion
      between the vesicle and membrane. To understand how the balance between the
      attractive and repulsive forces defines the equilibrium docked state we have
      developed a model that combines the mechanics of vesicle/membrane deformation
      with an apparently new coarse-grained model of the SNARE complex. The coarse
      grained model of the SNARE complex is calibrated by comparison with all-atom
      molecular dynamics simulations as well as by force measurements in laser tweezer
      experiments. The model for vesicle/membrane interactions includes the forces
      produced by membrane deformation and hydration or electrostatic repulsion.
      Combining these two parts, the coarse-grained model of the SNARE complex with
      membrane mechanics, we study how the equilibrium docked state varies with the
      number of SNARE complexes. We find that a single SNARE complex is able to bring a
      typical synaptic vesicle to within a distance of ~ 3 nm from the membrane.
      Further addition of SNARE complexes shortens this distance, but an overdocked
      state of >4-6 SNAREs actually increases the equilibrium distance.

PMID- 25954884
TI  - Mechanical heterogeneity favors fragmentation of strained actin filaments.
AB  - We present a general model of actin filament deformation and fragmentation in
      response to compressive forces. The elastic free energy density along filaments
      is determined by their shape and mechanical properties, which were modeled in
      terms of bending, twisting, and twist-bend coupling elasticities. The elastic
      energy stored in filament deformation (i.e., strain) tilts the fragmentation
      annealing reaction free-energy profile to favor fragmentation. The energy
      gradient introduces a local shear force that accelerates filament intersubunit
      bond rupture. The severing protein, cofilin, renders filaments more compliant in
      bending and twisting. As a result, filaments that are partially decorated with
      cofilin are mechanically heterogeneous (i.e., nonuniform) and display asymmetric
      shape deformations and energy profiles distinct from mechanically homogenous
      (i.e., uniform), bare actin, or saturated cofilactin filaments. The local
      buckling strain depends on the relative size of the compliant segment as well as
      the bending and twisting rigidities of flanking regions. Filaments with a single
      bare/cofilin-decorated boundary localize energy and force adjacent to the
      boundary, within the compliant cofilactin segment. Filaments with small cofilin
      clusters were predicted to fragment within the compliant cofilactin rather than
      at boundaries. Neglecting contributions from twist-bend coupling elasticity
      underestimates the energy density and gradients along filaments, and thus the net
      effects of filament strain to fragmentation. Spatial confinement causes compliant
      cofilactin segments and filaments to adopt higher deformation modes and store
      more elastic energy, thereby promoting fragmentation. The theory and simulations
      presented here establish a quantitative relationship between actin filament
      fragmentation thermodynamics and elasticity, and reveal how local discontinuities
      in filament mechanical properties introduced by regulatory proteins can modulate
      both the severing efficiency and location along filaments. The emergent behavior
      of mechanically heterogeneous filaments, particularly under confinement,
      emphasizes that severing in cells is likely to be influenced by multiple physical
      and chemical factors. 

PMID- 25954885
TI  - Constant-pH Molecular Dynamics Study of Kyotorphin in an Explicit Bilayer.
AB  - To our knowledge, we present the first constant-pH molecular dynamics study of
      the neuropeptide kyotorphin in the presence of an explicit lipid bilayer. The
      overall conformation freedom of the peptide was found to be affected by the
      interaction with the membrane, in accordance with previous results using
      different methodologies. Analysis of the interactions between the N-terminus
      amine group of the peptide and several lipid atoms shows that the membrane is
      able to stabilize both ionized and neutral forms of kyotorphin, resulting in a
      pKa value that is similar to the one obtained in water. This illustrates how a
      detailed molecular model of the membrane leads to rather different results than
      would be expected from simply regarding it as a low-dielectric slab. 

PMID- 25954886
TI  - Flanking A.T basepairs destabilize the B(*) conformation of DNA A-tracts.
AB  - Capillary electrophoresis has been used to characterize the interaction of
      monovalent cations with 26-basepair DNA oligomers containing A-tracts embedded in
      flanking sequences with different basepair compositions. A 26-basepair random
      sequence oligomer was used as the reference; lithium and tetrabutylammonium
      (TBA(+)) ions were used as the probe ions. The free solution mobilities of the A
      tract and random-sequence oligomers were identical in solutions containing <~ 100
      mM cation. At higher cation concentrations, the A-tract oligomers migrated faster
      than the reference oligomer in TBA(+) and slower than the reference in Li(+).
      Hence, cations of different sizes can interact very differently with DNA A
      tracts. The increased mobilities observed in TBA(+) suggest that the large
      hydrophobic TBA(+) ions are preferentially excluded from the vicinity of the A
      tract minor groove, increasing the effective net charge of the A-tract oligomers
      and increasing the mobility. By contrast, Li(+) ions decrease the mobility of A
      tract oligomers because of the preferential localization of Li(+) ions in the
      narrow A-tract minor groove. Embedding the A-tracts in AT-rich flanking sequences
      markedly alters preferential interactions of monovalent cations with the B(*)
      conformation. Hence, A-tracts embedded in genomic DNA may or may not interact
      preferentially with monovalent cations, depending on the relative number of A . T
      basepairs in the flanking sequences.

PMID- 25954887
TI  - A kinetic study of ovalbumin fibril formation: the importance of fragmentation
      and end-joining.
AB  - The ability to control the morphologies of biomolecular aggregates is a central
      objective in the study of self-assembly processes. The development of predictive
      models offers the surest route for gaining such control. Under the right
      conditions, proteins will self-assemble into fibers that may rearrange themselves
      even further to form diverse structures, including the formation of closed loops.
      In this study, chicken egg white ovalbumin is used as a model for the study of
      fibril loops. By monitoring the kinetics of self-assembly, we demonstrate that
      loop formation is a consequence of end-to-end association between protein
      fibrils. A model of fibril formation kinetics, including end-joining, is
      developed and solved, showing that end-joining has a distinct effect on the
      growth of fibrillar mass density (which can be measured experimentally),
      establishing a link between self-assembly kinetics and the underlying growth
      mechanism. These results will enable experimentalists to infer fibrillar
      morphologies from an appropriate analysis of self-assembly kinetic data. 

PMID- 25954888
TI  - Force-sensitive autoinhibition of the von Willebrand factor is mediated by
      interdomain interactions.
AB  - Von Willebrand factor (VWF) plays a central role in hemostasis. Triggered by
      shear-stress, it adheres to platelets at sites of vascular injury. Inactivation
      of VWF has been associated to the shielding of its adhesion sites and proteolytic
      cleavage. However, the molecular nature of this shielding and its coupling to
      cleavage under shear-forces in flowing blood remain unknown. In this study, we
      describe, to our knowledge, a new force-sensory mechanism for VWF-platelet
      binding, which addresses these questions, based on a combination of molecular
      dynamics (MD) simulations, atomic force microscopy (AFM), and microfluidic
      experiments. Our MD simulations demonstrate that the VWF A2 domain targets a
      specific region at the VWF A1 domain, corresponding to the binding site of the
      platelet glycoprotein Ibalpha (GPIbalpha) receptor, thereby causing its blockage.
      This implies autoinhibition of the VWF for the binding of platelets mediated by
      the A1-A2 protein-protein interaction. During force-probe MD simulations, a
      stretching force dissociated the A1A2 complex, thereby unblocking the GPIbalpha
      binding site. Dissociation was found to be coupled to the unfolding of the A2
      domain, with dissociation predominantly occurring before exposure of the cleavage
      site in A2, an observation that is supported by our AFM experiments. This
      suggests that the A2 domain prevents platelet binding in a force-dependent
      manner, ensuring that VWF initiates hemostasis before inactivation by proteolytic
      cleavage. Microfluidic experiments with an A2-deletion VWF mutant resulted in
      increased platelet binding, corroborating the key autoinhibitory role of the A2
      domain within VWF multimers. Overall, autoinhibition of VWF mediated by force
      dependent interdomain interactions offers the molecular basis for the shear
      sensitive growth of VWF-platelet aggregates, and might be similarly involved in
      shear-induced VWF self-aggregation and other force-sensing functions in
      hemostasis. 

PMID- 25954889
TI  - Molecular investigations into the mechanics of a muscle anchoring complex.
AB  - The titin-telethonin complex, essential for anchoring filaments in the Z-disk of
      the sarcomere, is composed of immunoglobulin domains. Surprisingly, atomic force
      microscopy experiments showed that it resists forces much higher than the typical
      immunoglobulin domain and that the force distribution is unusually broad. To
      investigate the origin of this behavior, we developed a multiscale simulation
      approach, combining minimalist and atomistic models (SOP-AT). By following the
      mechanical response of the complex on experimental timescales, we found that the
      mechanical stability of titin-telethonin is modulated primarily by the strength
      of contacts between telethonin and the two titin chains, and secondarily by the
      timescales of conformational excursions inside telethonin and the pulled titin
      domains. Importantly, the conformational transitions executed by telethonin in
      simulations support its proposed role in mechanosensing. Our SOP-AT computational
      approach thus provides a powerful tool for the exploration of the link between
      conformational diversity and the broadness of the mechanical response, which can
      be applied to other multidomain complexes. 

PMID- 25954890
TI  - A flexible nanoarray approach for the assembly and probing of molecular
      complexes.
AB  - Immobilization is a key step involved in probing molecular interactions using
      single-molecule force spectroscopy methods, including atomic force microscopy
      (AFM). To our knowledge, we describe a novel approach termed flexible nanoarray
      (FNA) in which the interaction between the two internally immobilized amyloid
      beta peptides is measured by pulling of the tether. The FNA tether was
      synthesized with nonnucleotide phosphoramidite monomers using the DNA synthesis
      chemistry. The two anchoring points for immobilization of the peptides inside the
      tether were incorporated at defined distances between them and from the ends of
      the polymer. Decamers of amyloid beta peptide capable of dimer formation were
      selected as a test system. The formation of the peptide dimers was verified by
      AFM force spectroscopy by pulling the tether at the ends. In these experiments,
      the thiolated end of the FNA tether was covalently immobilized on the AFM
      substrate functionalized with maleimide. The other end of the FNA tether was
      functionalized with biotin to form a noncovalent link with the streptavidin
      functionalized AFM tip during the approach stage. The dimers' rupture fingerprint
      was unambiguously identified on the force curves by its position and the force
      value. The FNA design allowed reversible experiments in which the monomers were
      allowed to associate after the rupture of the dimers by performing the approach
      stage before the rupture of the biotin-streptavidin link. This suggests that the
      FNA technique is capable of analyzing multiple intermolecular interactions in the
      same molecular complex. The computational analysis showed that the tethered
      peptides assemble into the same dimer structure as that formed by nontethered
      peptides, suggesting that the FNA tether has the necessary flexibility to enable
      assembly of the dimer even during the course of the force spectroscopy
      experiment. 

PMID- 25954891
TI  - Direct Sensing and Discrimination among Ubiquitin and Ubiquitin Chains Using
      Solid-State Nanopores.
AB  - Nanopore sensing involves an electrophoretic transport of analytes through a
      nanoscale pore, permitting label-free sensing at the single-molecule level.
      However, to date, the detection of individual small proteins has been
      challenging, primarily due to the poor signal/noise ratio that these molecules
      produce during passage through the pore. Here, we show that fine adjustment of
      the buffer pH, close to the isoelectric point, can be used to slow down the
      translocation speed of the analytes, hence permitting sensing and
      characterization of small globular proteins. Ubiquitin (Ub) is a small protein of
      8.5 kDa, which is well conserved in all eukaryotes. Ub conjugates to proteins as
      a posttranslational modification called ubiquitination. The immense diversity of
      Ub substrates, as well as the complexity of Ub modification types and the
      numerous physiological consequences of these modifications, make Ub and Ub chains
      an interesting and challenging subject of study. The ability to detect Ub and to
      identify Ub linkage type at the single-molecule level may provide a novel tool
      for investigation in the Ub field. This is especially adequate because, for most
      ubiquitinated substrates, Ub modifies only a few molecules in the cell at a given
      time. Applying our method to the detection of mono- and poly-Ub molecules, we
      show that we can analyze their characteristics using nanopores. Of particular
      importance is that two Ub dimers that are equal in molecular weight but differ in
      3D structure due to their different linkage types can be readily discriminated.
      Thus, to our knowledge, our method offers a novel approach for analyzing proteins
      in unprecedented detail using solid-state nanopores. Specifically, it provides
      the basis for development of single-molecule sensing of differently ubiquitinated
      substrates with different biological significance. Finally, our study serves as a
      proof of concept for approaching nanopore detection of sub-10-kDa proteins and
      demonstrates the ability of this method to differentiate among native and
      untethered proteins of the same mass.

PMID- 25954892
TI  - The folding unit of phosphofructokinase-2 as defined by the biophysical
      properties of a monomeric mutant.
AB  - Escherichia coli phosphofructokinase-2 (Pfk-2) is an obligate homodimer that
      follows a highly cooperative three-state folding mechanism N2 <-> 2I <-> 2U. The
      strong coupling between dissociation and unfolding is a consequence of the
      structural features of its interface: a bimolecular domain formed by intertwining
      of the small domain of each subunit into a flattened beta-barrel. Although
      isolated monomers of E. coli Pfk-2 have been observed by modification of the
      environment (changes in temperature, addition of chaotropic agents), no isolated
      subunits in native conditions have been obtained. Based on in silico estimations
      of the change in free energy and the local energetic frustration upon binding, we
      engineered a single-point mutant to destabilize the interface of Pfk-2. This
      mutant, L93A, is an inactive monomer at protein concentrations below 30 MUM, as
      determined by analytical ultracentrifugation, dynamic light scattering, size
      exclusion chromatography, small-angle x-ray scattering, and enzyme kinetics.
      Active dimer formation can be induced by increasing the protein concentration and
      by addition of its substrate fructose-6-phosphate. Chemical and thermal unfolding
      of the L93A monomer followed by circular dichroism and dynamic light scattering
      suggest that it unfolds noncooperatively and that the isolated subunit is
      partially unstructured and marginally stable. The detailed structural features of
      the L93A monomer and the F6P-induced dimer were ascertained by high-resolution
      hydrogen/deuterium exchange mass spectrometry. Our results show that the isolated
      subunit has overall higher solvent accessibility than the native dimer, with the
      exception of residues 240-309. These residues correspond to most of the beta
      meander module and show the same extent of deuterium uptake as the native dimer.
      Our results support the idea that the hydrophobic core of the isolated monomer of
      Pfk-2 is solvent-penetrated in native conditions and that the beta-meander module
      is not affected by monomerizing mutations.

PMID- 25954893
TI  - Peptide Binding to a PDZ Domain by Electrostatic Steering via Nonnative Salt
      Bridges.
AB  - We have captured the binding of a peptide to a PDZ domain by unbiased molecular
      dynamics simulations. Analysis of the trajectories reveals on-pathway encounter
      complex formation, which is driven by electrostatic interactions between
      negatively charged carboxylate groups in the peptide and positively charged side
      chains surrounding the binding site. In contrast, the final stereospecific
      complex, which matches the crystal structure, features completely different
      interactions, namely the burial of the hydrophobic side chain of the peptide C
      terminal residue and backbone hydrogen bonds. The simulations show that nonnative
      salt bridges stabilize kinetically the encounter complex during binding.
      Unbinding follows the inverse sequence of events with the same nonnative salt
      bridges in the encounter complex. Thus, in contrast to protein folding, which is
      driven by native interactions, the binding of charged peptides can be steered by
      nonnative interactions, which might be a general mechanism, e.g., in the
      recognition of histone tails by bromodomains. 

PMID- 25954894
TI  - FtsZ Polymers Tethered to the Membrane by ZipA Are Susceptible to Spatial
      Regulation by Min Waves.
AB  - Bacterial cell division is driven by an FtsZ ring in which the FtsZ protein
      localizes at mid-cell and recruits other proteins, forming a divisome. In
      Escherichia coli, the first molecular assembly of the divisome, the proto-ring,
      is formed by the association of FtsZ polymers to the cytoplasmic membrane through
      the membrane-tethering FtsA and ZipA proteins. The MinCDE system plays a major
      role in the site selection of the division ring because these proteins oscillate
      from pole to pole in such a way that the concentration of the FtsZ-ring
      inhibitor, MinC, is minimal at the cell center, thus favoring FtsZ assembly in
      this region. We show that MinCDE drives the formation of waves of FtsZ polymers
      associated to bilayers by ZipA, which propagate as antiphase patterns with
      respect to those of Min as revealed by confocal fluorescence microscopy. The
      emergence of these FtsZ waves results from the displacement of FtsZ polymers from
      the vicinity of the membrane by MinCD, which efficiently competes with ZipA for
      the C-terminal region of FtsZ, a central hub for multiple interactions that are
      essential for division. The coupling between FtsZ polymers and Min is enhanced at
      higher surface densities of ZipA or in the presence of crowding agents that favor
      the accumulation of FtsZ polymers near the membrane. The association of FtsZ
      polymers to the membrane modifies the response of FtsZ to Min, and comigrating
      Min-FtsZ waves are observed when FtsZ is free in solution and not attached to the
      membrane by ZipA. Taken together, our findings show that the dynamic Min patterns
      modulate the spatial distribution of FtsZ polymers in controlled minimal
      membranes. We propose that ZipA plays an important role in mid-cell recruitment
      of FtsZ orchestrated by MinCDE. 

PMID- 25954895
TI  - Anomalous extracellular diffusion in rat cerebellum.
AB  - Extracellular space (ECS) is a major channel transporting biologically active
      molecules and drugs in the brain. Diffusion-mediated transport of these
      substances is hindered by the ECS structure but the microscopic basis of this
      hindrance is not fully understood. One hypothesis proposes that the hindrance
      originates in large part from the presence of dead-space (DS) microdomains that
      can transiently retain diffusing molecules. Because previous theoretical and
      modeling work reported an initial period of anomalous diffusion in similar
      environments, we expected that brain regions densely populated by DS microdomains
      would exhibit anomalous extracellular diffusion. Specifically, we targeted
      granular layers (GL) of rat and turtle cerebella that are populated with large
      and geometrically complex glomeruli. The integrative optical imaging (IOI) method
      was employed to evaluate diffusion of fluorophore-labeled dextran (MW 3000) in
      GL, and the IOI data analysis was adapted to quantify the anomalous diffusion
      exponent dw from the IOI records. Diffusion was significantly anomalous in rat
      GL, where dw reached 4.8. In the geometrically simpler turtle GL, dw was elevated
      but not robustly anomalous (dw = 2.6). The experimental work was complemented by
      numerical Monte Carlo simulations of anomalous ECS diffusion in several three
      dimensional tissue models containing glomeruli-like structures. It demonstrated
      that both the duration of transiently anomalous diffusion and the anomalous
      exponent depend on the size of model glomeruli and the degree of their wrapping.
      In conclusion, we have found anomalous extracellular diffusion in the GL of rat
      cerebellum. This finding lends support to the DS microdomain hypothesis.
      Transiently anomalous diffusion also has a profound effect on the spatiotemporal
      distribution of molecules released into the ECS, especially at diffusion
      distances on the order of a few cell diameters, speeding up short-range diffusion
      mediated signals in less permeable structures.

PMID- 25954896
TI  - Mechanochemical symmetry breaking in Hydra aggregates.
AB  - Tissue morphogenesis comprises the self-organized creation of various patterns
      and shapes. Although detailed underlying mechanisms are still elusive in many
      cases, an increasing amount of experimental data suggests that chemical morphogen
      and mechanical processes are strongly coupled. Here, we develop and test a
      minimal model of the axis-defining step (i.e., symmetry breaking) in aggregates
      of the Hydra polyp. Based on previous findings, we combine osmotically driven
      shape oscillations with tissue mechanics and morphogen dynamics. We show that the
      model incorporating a simple feedback loop between morphogen patterning and
      tissue stretch reproduces a wide range of experimental data. Finally, we compare
      different hypothetical morphogen patterning mechanisms (Turing, tissue-curvature,
      and self-organized criticality). Our results suggest the experimental
      investigation of bigger (i.e., multiple head) aggregates as a key step for a
      deeper understanding of mechanochemical symmetry breaking in Hydra. 

PMID- 25954897
TI  - Delayed feedback model of axonal length sensing.
AB  - A fundamental question in cell biology is how the sizes of cells and organelles
      are regulated at various stages of development. Size homeostasis is particularly
      challenging for neurons, whose axons can extend from hundreds of microns to
      meters (in humans). Recently, a molecular-motor-based mechanism for axonal length
      sensing has been proposed, in which axonal length is encoded by the frequency of
      an oscillating retrograde signal. In this article, we develop a mathematical
      model of this length-sensing mechanism in which advection-diffusion equations for
      bidirectional motor transport are coupled to a chemical signaling network. We
      show that chemical oscillations emerge due to delayed negative feedback via a
      Hopf bifurcation, resulting in a frequency that is a monotonically decreasing
      function of axonal length. Knockdown of either kinesin or dynein causes an
      increase in the oscillation frequency, suggesting that the length-sensing
      mechanism would produce longer axons, which is consistent with experimental
      findings. One major prediction of the model is that fluctuations in the transport
      of molecular motors lead to a reduction in the reliability of the frequency
      encoding mechanism for long axons. 

PMID- 25954898
TI  - Community sewage sensors for monitoring public health.

PMID- 25954899
TI  - Fruit and vegetable intake assessed by food frequency questionnaire and plasma
      carotenoids: a validation study in adults.
AB  - Dietary validation studies of self-reported fruit and vegetable intake should
      ideally include measurement of plasma biomarkers of intake. The aim was to
      conduct a validation study of self-reported fruit and vegetable intakes in
      adults, using the Australian Eating Survey (AES) food frequency questionnaire
      (FFQ), against a range of plasma carotenoids. Dietary intakes were assessed using
      the semi-quantitative 120 item AES FFQ. Fasting plasma carotenoids (alpha- and
      beta-carotene, lutein/zeaxanthin, lycopene and cryptoxanthin) were assessed using
      high performance liquid chromatography in a sample of 38 adult volunteers (66%
      female). Significant positive correlations were found between FFQ and plasma
      carotenoids for alpha-carotene, beta-carotene and lutein/zeaxanthin (52%, 47%,
      26%, p < 0.001, 0.003, 0.041; respectively) and relationships between plasma
      carotenoids (except lycopene) and weight status metrics (BMI, waist
      circumference, fat mass) were negative and highly significant. The results of the
      current study demonstrate that carotenoid intakes as assessed by the AES FFQ are
      significantly related to plasma concentrations of alpha-carotene, beta-carotene
      and lutein/zeaxanthin, the carotenoids commonly found in fruit and vegetables.
      Lower levels of all plasma carotenoids, except lycopene, were found in
      individuals with higher BMI. We conclude that the AES can be used to measure
      fruit and vegetable intakes with confidence. 

PMID- 25954900
TI  - Determination of zinc status in humans: which indicator should we use?
AB  - Zinc deficiency has serious wide-ranging health consequences and is thought to be
      one of the most prevalent micronutrient deficiencies in the world. However,
      reliable indicators or biomarkers to assess zinc status are not available at
      present. Indirect indicators such as the prevalence of stunting or anemia, iron
      deficiency, as well as more direct indicators such as plasma zinc concentrations
      are being used at present to estimate the prevalence of zinc deficiency in
      populations. However, as this paper shows by using data from a recent national
      micronutrient survey in Vietnam, the estimates of the prevalence of zinc
      deficiency using these different indicators can vary widely, leading to
      inconsistencies. In this paper, zinc deficiency among children is four times more
      prevalent than iron deficiency and 2.3 times more than stunting prevalence for
      example. This can lead not only to confusion concerning the real extent of the
      prevalence of zinc deficiency in populations, but also makes it hard to inform
      policy on whether action is needed or not. Moreover, evaluation of programs is
      hampered by the lack of a clear indicator. Efforts should be made to identify the
      most suitable indicator to evaluate the impact of programs aimed at improving
      zinc status and health of populations. 

PMID- 25954901
TI  - Vitamin D as a Resilience Factor, Helpful for Survival of Potentially Fatal
      Conditions: A Hypothesis Emerging from Recent Findings of the ESTHER Cohort Study
      and the CHANCES Consortium.
AB  - There is debate on whether vitamin D deficiency is a risk factor for major
      chronic diseases and premature death or whether observed associations were just
      confounded by general health status. Here, we review recent results from the
      Epidemiologische Studie zu Chancen der Verhutung, Fruherkennung und optimierten
      Therapie chronischer Erkrankungen in der alteren Bevolkerung (ESTHER) cohort
      study and the Consortium on Heatlh and Ageing: Network of Cohorts from Europe and
      the United States (CHANCES) that suggest that vitamin D deficiency may not be a
      risk factor for the development of cardiovascular diseases and cancer but may be
      a risk factor for fatal instances of these diseases. Furthermore, analyses
      comprehensively adjusted for the health status showed that the association of
      vitamin D and mortality was very likely not confounded by general health status.
      These results suggest that vitamin D could be a marker of resilience to fatality
      of potentially fatal diseases. Sufficient vitamin D serum concentrations may be
      needed to regulate the response of the immune system when it is challenged by
      severe diseases to prevent a fatal course of the disease. If this hypothesis can
      be verified through basic research studies and adequately designed randomized
      controlled trials, it could have important public health implications because
      vitamin D deficiency is very common worldwide, and interventions could be
      implemented easily. 

PMID- 25954903
TI  - miR-34a inhibits the migration and invasion of esophageal squamous cell carcinoma
      by targeting Yin Yang-1.
AB  - Esophageal squamous cell carcinoma (ESCC), one of the most common
      gastrointestinal tumors, is known for its high mortality rate. microRNAs (miRNAs)
      have been reported to play important regulatory roles in cancer metastasis and
      progression. miR-34a has been demonstrated to be associated with the development
      of and metastasis in certain types of cancer via various target genes, but its
      function and targets in ESCC are unknown. The aim of this study was to examine
      whether the expression of miR-34a was significantly decreased in ESCC tissues,
      compared with normal esophageal tissues using RT-PCR and western blot analysis.
      The results showed that miR-34a overexpression increased apoptosis and decreased
      clonogenic formation, but inhibited invasion and migration in ESCC cells by
      suppressing MMP-2 and -9 expression. Yin Yang-1 (YY1), a widely distributed
      transcription factor that belongs to the GLI-Kruppel class of zinc finger
      proteins, was found to be a direct target of miR-34a in ESCC cell lines. Rescue
      experiments indicated that the suppressive effect of miR-34a on invasion and
      migration was mediated by activating YY1 expression. Results of the present study
      showed that miR-34a is associated with ESCC migration and provides a potential
      therapeutic and diagnostic target for ESCC.

PMID- 25954904
TI  - "I Am Administering Medication-Please Do Not Interrupt Me": Red Tabards
      Preventing Interruptions as Perceived by Surgical Patients.
AB  - INTRODUCTION: The recent introduction of red tabards aimed at avoiding
      interruptions during medication rounds has generated scientific and media debate,
      which is still ongoing. The principal aim of this study was to evaluate patients'
      perceptions of 3 different red tabards; the secondary aim was to explore
      individual factors associated with the negative perceptions that emerged.
      METHODS: Eligible patients had to be admitted to the selected general surgical
      department and give written informed consent. A total of 104 patients were
      interviewed. Three real-sized red tabards, made with laminated paper and
      displaying different messages, were shown over 3 days to each patient involved.
      RESULTS: Despite displaying different messages, from asking everyone not to
      disturb to allowing only patients to interrupt, patients perceived the tabards as
      directed at themselves. A different risk of preventing patients from
      communicating urgent needs emerged. The first tabard I am administering
      medication-Please do not interrupt me was most at risk to inhibit the patient. A
      negative impact was reported by 44 patients (42.3%) for the first tabard, 50
      (48.0%) for the second tabard, and 40 (38.4%) for the third. In the logistic
      regression, only 2 independent factors were significantly associated with the
      negative perception of the message reported on the tabards: a positive attitude
      to interrupting nurses and receiving medication during their time in hospital.
      However, the variance explained by these factors ranges from 9.4% to 18.3%.
      CONCLUSIONS: On the basis of the findings that emerged, the adoption of the
      tabards should be evaluated considering the benefits already documented, and the
      potential negative effects that emerged on patients, which may be influenced by
      cultural and linguistic aspects. Wearing the tabard with the message reported on
      the back, directed to the staff and not the patients, may have less negative
      effects on patients; in addition, using a different color not to alarm the
      patients may be useful. In addition, comparing the red tabard effects with other
      strategies introduced to deal with avoidable interruptions (e.g., "no
      interruption zone") to gain a comprehensive picture regarding benefits/harm is
      also important.

PMID- 25954902
TI  - Phylum level change in the cecal and fecal gut communities of rats fed diets
      containing different fermentable substrates supports a role for nitrogen as a
      factor contributing to community structure.
AB  - Fermentation differs between the proximal and distal gut but little is known
      regarding how the bacterial communities differ or how they are influenced by
      diet. In order to investigate this, we compared community diversity in the cecum
      and feces of rats by 16S rRNA gene content and DNA shot gun metagenomics after
      feeding purified diets containing different fermentable substrates. Gut community
      composition was dependent on the source of fermentable substrate included in the
      diet. Cecal communities were dominated by Firmicutes, and contained a higher
      abundance of Lachnospiraceae compared to feces. In feces, community structure was
      shifted by varying degrees depending on diet towards the Bacteroidetes, although
      this change was not always evident from 16S rRNA gene data. Multi-dimensional
      scaling analysis (PCoA) comparing cecal and fecal metagenomes grouped by location
      within the gut rather than by diet, suggesting that factors in addition to
      substrate were important for community change in the distal gut. Differentially
      abundant genes in each environment supported this shift away from the Firmicutes
      in the cecum (e.g., motility) towards the Bacteroidetes in feces (e.g.,
      Bacteroidales transposons). We suggest that this phylum level change reflects a
      shift to ammonia as the primary source of nitrogen used to support continued
      microbial growth in the distal gut. 

PMID- 25954905
TI  - Evaluation of Anticonvulsant, Antidepressant-, and Anxiolytic-like Effects of an
      Aqueous Extract from Cultured Mycelia of the Lingzhi or Reishi Medicinal Mushroom
      Ganoderma lucidum (Higher Basidiomycetes) in Mice.
AB  - Ganoderma lucidum is a well-known medicinal mushroom with a long history of use.
      This study was designed to assess the anticonvulsant potential of an aqueous
      extract from cultured G. lucidum mycelium in 3 acute seizure models: timed
      intravenous pentylenetetrazole infusion, maximal electroshock seizure threshold,
      and 6-Hz-induced psychomotor seizure tests in mice. Moreover, antidepressant-like
      and anxiolytic-like effects of G. lucidum were evaluated using the forced swim
      test and the elevated plus maze test in mice, respectively. No changes in seizure
      thresholds in the intravenous pentylenetetrazole and maximal electroshock seizure
      threshold tests after acute treatment with G. lucidum extract (200-600 mg/kg) was
      observed. However, the studied extract (100-400 mg/kg) significantly increased
      the threshold for psychomotor seizures in the 6-Hz seizure test. In the forced
      swim test, G. lucidum (100-400 mg/kg) significantly reduced the duration of
      immobility. No anxiolytic-like or sedative effects were reported in mice
      pretreated with the extract (400-600 mg/kg). G. lucidum extract (50-2400 mg/kg)
      did not produce toxic effects in the chimney test (motor coordination) or grip
      strength test (neuromuscular strength). Further studies are required to explain
      the neuropharmacological effects of G. lucidum and to identify its active
      ingredients that may affect seizure threshold, mood, or anxiety. 

PMID- 25954906
TI  - Systemic Screening of Strains of the Lion's Mane Medicinal Mushroom Hericium
      erinaceus (Higher Basidiomycetes) and Its Protective Effects on Abeta-Triggered
      Neurotoxicity in PC12 Cells.
AB  - Hericium erinaceus possesses multiple medicinal values. To date, however, there
      have been few studies of the systemic screening of H. erinaceus strains, and the
      neuroprotective effects of H. erinaceus prepared from homogenized, fresh fruiting
      bodies are not fully understood. In this study, 4 random primers were selected
      and used in random amplified polymorphic DNA (RAPD) polymerase chain reaction
      (PCR) to screen and evaluate the genetic diversity of 19 commercial strains of H.
      erinaceus from different localities in China. A total of 66 bands were obtained,
      and the percentage of polymorphic loci reached 80.30%. Five dendrograms were
      constructed based on RAPD by Jaccard cluster and within-group linkage analysis.
      Primer S20 as well as all 4 primers had great potential as specific primers for
      RAPD-PCR molecular identification and differentiation of H. erinaceus strains.
      Based on the results of submerged culture and fruiting body cultivation, strains
      HT-N, HT-J1, HT-C, and HT-M were identified as superior among the 19 H. erinaceus
      strains. Further study showed that the oral preparation of homogenized, fresh
      fruiting bodies of H. erinaceus could attenuate the Abeta25-35-triggered damage
      in PC12 cells by significantly increasing cell viability and by decreasing the
      release of lactate dehydrogenase. In conclusion, RAPD-PCR combined with liquid
      and solid cultures can be used well in the screening and identification of H.
      erinaceus strains, and products prepared from homogenized, fresh fruiting bodies
      of H. erinaceus had neuroprotective effects on PC12 cells. 

PMID- 25954907
TI  - Effects of Ganoderma lucidum (Higher Basidiomycetes) Extracts on the miRNA
      Profile and Telomerase Activity of the MCF-7 Breast Cancer Cell Line.
AB  - Ganoderma lucidum is a medicinal higher Basidiomycetes mushroom that exerts
      anticancer effects through several different mechanisms. This study investigated
      the effects of G. lucidum on the telomerase activity and microRNA (miRNA)
      profiles of MCF-7 cells. According to the cytotoxicity results, the G. lucidum
      ether extract exhibits the highest cytotoxic potency; therefore it was chosen for
      the subsequent telomerase activity assay and miRNA profiling. The telomerase
      activity observed in the cells treated with a half-maximal inhibitory
      concentration of G. lucidum ether extract (100 ug/mL in dimethyl sulfoxide) was
      32.2% lower than that of the control cells treated with 1% dimethyl sulfoxide.
      Among 1066 miRNAs, the most downregulated miRNA was hsa-miR-27a* (4.469-fold),
      and the most upregulated miRNA was hsa-miR-1285 (10.462-fold). A database search
      revealed the predicted miRNAs that target the catalytic subunit of the telomerase
      enzyme telomerase reverse transcriptase, and only miR-3687 (upregulated 2.153
      fold) and miR-1207-5p (upregulated 2.895-fold) were changed by at least 2-fold.
      The miRNA profile changes demonstrated in this study provide a data set regarding
      their effects on the pathways that regulate telomerase activity in MCF-7 breast
      cancer cells treated with G. lucidum. These data should aid the development of
      novel cancer treatment strategies. 

PMID- 25954908
TI  - Effect of UV-B Irradiation on Physiologically Active Substance Content and
      Antioxidant Properties of the Medicinal Caterpillar Fungus Cordyceps militaris
      (Ascomycetes).
AB  - Ultraviolet-B (UV-B) light irradiation is a well-known technique for converting
      vitamin D2 from ergosterol in mushroom fruit bodies. Mushrooms are a natural and
      nonanimal food source of vitamin D2. We studied the effect of UV-B light
      irradiation on the amount of vitamin D2 and physiologically active substances in
      Cordyceps militaris and their antioxidant properties. After UV-B irradiation for
      2 hours, the vitamin D2 content of freshly harvested C. militaris fruiting
      bodies, mycelia, whole submerged culture (WSC), and homogenized submerged culture
      (HSC) increased from 0 to 0.03 to 0.22 to 1.11 mg/g, but the ergosterol content
      was reduced from 1.36 to 2.50 to 1.24 to 2.06 mg/g, respectively. After UV-B
      irradiation, the amount of adenosine, cordycepin, and ergothioneine of fruiting
      bodies dramatically increased 32-128%, but the polysaccharide content slightly
      decreased 36%. The reverse trends were observed in mycelia, WSC, and HSC. UV-B
      irradiation could reduce the effective concentrations at 50% of fruiting bodies
      for ethanolic and hot water extracts in reducing power, scavenging, and chelating
      abilities, whereas mycelia, WSC, and HSC of ethanolic extracts increased
      effective concentrations at 50% in reducing power, scavenging, and chelating
      abilities. UV-B irradiation slightly increased flavonoid content (10-56%) and
      slightly affected total phenol content. 

PMID- 25954909
TI  - Mycochemical Investigation of the Turkey Tail Medicinal Mushroom Trametes
      versicolor (Higher Basidiomycetes): A Potential Application of the Isolated
      Compounds in Documented Pharmacological Studies.
AB  - The purpose of this study was to elucidate the chemical properties of the n
      hexane, chloroform, and ethyl acetate extracts of the fruiting body of the
      medicinal mushroom Trametes versicolor. The study led to the isolation of 5
      sterols, 2 triterpene derivatives, 1 hydroquinone-derived aromatic compound, and,
      finally, 1 cerebroside and 1 triglyceride derivative. These compounds were
      identified for first time in T. versicolor and were named as follows: 4
      isobutoxyphenyl palmitate (5), N-D-2'-hydroxyheptanoic-1-O-beta-D-glucopyranosyl
      9-methyl-4,8-sphinga-dienine(cerebroside) (6), 3beta-linoleyloxyergosta-7,22
      diene (7), 3beta-linoleyloxyergosta-7-ene (8), and betulinic acid (9). Other
      compounds elucidated in our study were ergosterol (1), ergosterol peroxide (2),
      trilinolein (3), ergosta-7, 22-dien-3beta-ol (4), and betuline (10). These
      compounds were obtained via column or thin-layer chromatography before being
      identified by nuclear magnetic resonance spectroscopic analyses and infrared
      data. In addition, the beneficial pharmacological effects of the compounds are
      described here. 

PMID- 25954910
TI  - Chemical Composition and Immunomodulatory Activity of Mycelia of the Hairy
      Bracket Mushroom, Trametes hirsuta (Higher Basidiomycetes).
AB  - Trametes hirsuta is a medicinal mushroom that produces laccase. Its mycelium is a
      by-product when this species is used for laccase production. Aiming to develop
      its potential medicinal value, we investigated the chemical composition and
      immunomodulatory activity of T. hirsuta mycelia (THM). Dried THM contained 26.06%
      protein, 1.15% fat, 57.87% carbohydrates, and 5.47% ash. Sixteen free amino acids
      (2.63% total content) and 6 5'-nucleotides (adenosine 5'-monophosphate, cytidine
      5'-monophosphate, guanosine 5'-monophosphate, uridine 5'-monophosphate,
      xanthosine 5'-monophosphate, and inosine 5'-monophosphate) constituting 0.275%
      were detected. Dominant sugars and polyols were fructose (2.47%), mannitol
      (2.03%), and glucose (1.8%); trehalose and arabinose contents were less than
      0.10%. Evaluation of immunomodulatory activity in mice showed that THM could
      improve macrophage phagocytic function and serum hemolysin concentrations, but
      only the low-dose group significantly enhanced the natural killer cell activity
      and increased the spleen index, and only the middle-dose group remarkably
      increased the thymus index. Therefore, T. hirsuta mycelia could enhance immune
      function in mice and have immunomodulatory activity. 

PMID- 25954911
TI  - The Effect of the Medicinal Mushrooms Agaricus brasiliensis and Ganoderma lucidum
      (Higher Basidiomycetes) on the Erythron System in Normal and Streptozotocin
      Induced Diabetic Rats.
AB  - Diabetes mellitus (DM) is accompanied by the development of hypoxia, which
      disturbs the physicochemical properties of the erythrocyte membrane and further
      leads to the occurrence of anemia and a reduction of the lifespan. In response,
      the body activates compensatory reactions directed at a renewal of the red blood
      cell pool and an increase in tissue oxygenation. In this study the influence of
      Agaricus brasiliensis and Ganoderma lucidum medicinal mushroom mycelia on the
      erythron system of control and streptozotocin (STZ)-induced diabetic rats were
      investigated. Wistar outbred white male rats were intraperitoneally injected with
      saline (control rats) or STZ (50 mg/kg, DM rats) and orally treated with placebo
      or submerged culture mycelium powder (1 g/kg/day) for 2 weeks. Peripheral blood
      erythrocytes were collected. Hypoglycemic effects of A. brasiliensis and G.
      lucidum occurred in the diabetic rats, as evidenced by decreased blood glucose
      and glycosylated hemoglobin concentrations. In STZ-diabetic animals treated with
      submerged culture mycelium powder, an increase in the number of erythrocytes in
      the bloodstream (an antianemic effect), erythrocyte resistance to acid hemolysis,
      and the normalization of fetal hemoglobin concentrations, along with the
      intensification of erythropoiesis were observed. In conclusion, our results
      suggest that in diabetic animals A. brasiliensis and G. lucidum have therapeutic
      effects that manifest in hypoglycemic and antianemic action. 

PMID- 25954912
TI  - Comparison of antioxidant and antiproliferation activities of polysaccharides
      from eight species of medicinal mushrooms.
AB  - Polysaccharides from mushrooms including Pleurotus eryngii, P. ostreatus, P.
      nebrodensis, Lentinus edodes, Hypsizygus marmoreus, Flammulina velutipes,
      Ganoderma lucidum, and Hericium erinaceus were isolated by water extraction and
      alcohol precipitation. Our results suggest that all tested polysaccharides have
      the significant antioxidant capacities of scavenging free radicals (1,1-diphenyl
      2-picrylhydrazyl and hydroxyl radicals). Among them, the H. erinaceus
      polysaccharide exhibits the highest 1,1-diphenyl-2-picrylhydrazyl radical
      scavenging activity, whereas the L. edodes polysaccharide shows the strongest
      scavenging ability for hydroxyl radicals. Furthermore, using the MCF-7 breast
      cancer cell line and HeLa cells, all 8 selected polysaccharides are able to
      inhibit the proliferation of tumor cells, but the strength of inhibition varied
      depending on the mushroom species and the concentration used. Notably, G. lucidum
      polysaccharide shows the highest inhibition activity on MCF-7 cells. By
      comparison, H. erinaceus polysaccharide has the strongest inhibitory effect on
      HeLa cells. Moreover, high-performance liquid chromatography with a carbohydrate
      analysis column showed significant differences in polysaccharide components among
      these mushrooms. Thus our data suggest that the different species of mushrooms
      have the variable functions because of their own specific polysaccharide
      components. The 8 mushroom polysaccharides have the potential to be used as
      valuable functional food additives or sources of therapeutic agents for
      antioxidant and cancer treatments, especially polysaccharides from H. erinaceus,
      L. edodes, and G. lucidum. 

PMID- 25954913
TI  - Chemical Characterization and In Vitro Antioxidant Activity Evaluation of
      Polysaccharides from the Fruiting Bodies of the Red Heart Mushroom Phellinus pini
      (Higher Basidiomycetes).
AB  - Phellinus pini is a precious medicinal mushroom. Three water-soluble fractions of
      crude polysaccharides (PP30, PP60, and PP80) were obtained from the fruiting
      bodies of Ph. Pini. The basic chemical characterization and in vitro antioxidant
      activity of these 3 polysaccharides were determined. All 3 crude polysaccharides
      were heteropolysaccharide complexes with a small amount of protein (1.14-2.55%)
      and uronic acid (2.06-4.11%). The monosaccharide composition of PP30, PP60, and
      PP80, as a molar ratio, was mannose (1.00):glucose (18.7):galactose (0.92),
      fucose (0.47):3-0-Me-Gal (0.51):mannose (1.00):glucose (7.86):galactose (1.10),
      and rhamnose (0.12):fucose (0.32):xylose (0.17):3-0-Me-Gal (0.26):mannose
      (1.00):glucose (4.79):galactose (0.53), respectively. The in vitro antioxidant
      activities of crude polysaccharides were evaluated by 2,2-diphenyl-1
      picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium
      salt, hydroxyl radical, and ferric-reducing antioxidant power methods. The
      antioxidant data obtained using these methods were in accordance with each other
      and decreased in the same order of PP80 > PP60 > PP30 at a concentration of 0.1
      2.5 mg/mL. 

PMID- 25954914
TI  - Immunomodulating and Antiprotozoal Effects of Different Extracts of the Oyster
      Culinary-Medicinal Mushroom Pleurotus ostreatus (Higher Basidiomycetes) Against
      Coccidiosis in Broiler.
AB  - The culinary-medicinal oyster mushroom Pleurotus ostreatus, procured from local
      sources, was processed for hot water and methanolic extraction. Extracts obtained
      were subjected to proximate analysis to determine the amount of crude protein,
      crude fiber, ash, ether, and nitrogen-free extracts. These extracts were
      evaluated for immunomodulating and antiprotozoal effects against coccidiosis in a
      broiler. Cellular immune investigation revealed significantly higher (P < 0.05)
      lymphoproliferative response to phytohemagglutinin-P in groups administered P.
      ostreatus extracts compared with controls. Humoral immune investigation revealed
      higher immunoglobulin (total Ig, IgG, and IgM) titers against sheep red blood
      cells in treated groups compared with controls. However, nonsignificant (P >
      0.05) findings were observed in investigations of lymphoid organs. Antiprotozoal
      studies revealed a significantly higher (P < 0.05) percentage of protection
      against coccidiosis in groups administered P. ostreatus extracts when compared
      with controls. Moreover, lesion scoring and oocysts per gram of droppings
      observed in the control group were significantly higher (P < 0.05) compared with
      those in groups administered hot water and methanolic extracts of P. ostreatus.
      Results concluded that hot water and methanolic extracts of P. ostreatus had
      strong immune-enhancing activities. Further, these extracts also had excellent
      antiprotozoal activities against coccidiosis in a broiler. 

PMID- 25954916
TI  - Effect of Sulfuric and Triflic Acids on the Hydration of Vanadium Cations: An ab
      Initio Study.
AB  - Vanadium redox flow batteries (VRFBs) may be a promising solution for large-scale
      energy storage applications, but the crossover of any of the redox active species
      V(2+), V(3+), VO(2+), and VO2(+) through the ion exchange membrane will result in
      self-discharge of the battery. Hence, a molecular level understanding of the
      states of vanadium cations in the highly acidic environment of a VRFB is needed.
      We examine the effects of sulfuric and triflic (CF3SO3H) acids on the hydration
      of vanadium species as they mimic the electrolyte and functional group of
      perfluorosulfonic acid (PFSA) membranes. Hybrid density functional theory in
      conjunction with a continuum solvation model was utilized to obtain the local
      structures of the hydrated vanadium cations in proximity to H2SO4, CF3SO3H, and
      their conjugate anions. The results indicate that none of these species
      covalently bond to the vanadium cations. The hydration structure of V(3+) is more
      distorted than that of V(2+) in an acidic medium. The oxo-group of VO2(+) is
      protonated by either acid, in contrast to VO(2+) which is not protonated. The
      atomic partial charge of the four oxidation states of vanadium varies from +1.7
      to +2.0. These results provide the local solvation structures of vanadium cations
      in the VRFBs environment that are directly related to the electrolytes stability
      and diffusion of vanadium ions into the membrane. 

PMID- 25954915
TI  - Association analysis of polymorphisms of the CRHR1 gene with infantile spasms.
AB  - While >200 types of etiologies have been shown to be involved in the pathogenesis
      of infantile spasms, the pathophysiology of infantile spasms remains largely
      elusive. Pre-natal stress and hypothalamic-pituitary-adrenal axis dysfunction
      were shown to be involved in the development of infantile spasms. To test the
      genetic association between the CRHR1 gene, which encodes the corticotrophin
      releasing hormone (CRH) receptor, and infantile spasms, five single nucleotide
      polymorphisms (SNPs) in the CRHR1 gene were genotyped in a sample set of 128
      cases with infantile spasms and 131 healthy controls. Correlation analysis was
      performed on the genotyped data. Under the assumption of the dominant model, the
      selected five SNPs, rs4458044, rs171440, rs17689966, rs28364026 and rs242948,
      showed no association with the risk of infantile spasms and the effectiveness of
      adrenocorticotropic hormone treatment. In addition, subsequent haplotype analysis
      suggested none of them was associated with infantile spasms. In conclusion, the
      experimental results of the present study suggested no association between the
      CRHR1 gene and infantile spasms in a Chinese population.

PMID- 25954919
TI  - Reduction of autonomic regulation in children and adolescents with conversion
      disorders.
AB  - OBJECTIVE: Conversion symptoms--functional neurological disturbances of body
      function--occur in association with extreme arousal, often in the context of
      emotional distress. The mechanisms that determine how and why such symptoms occur
      remain unknown. In this study, we used cardiac measures to assess arousal and
      cardiac autonomic regulation in children and adolescents who presented with acute
      conversion symptoms. METHODS: Heart rate was recorded in 57 children and
      adolescents (41 girls; 8.5-18 years old) with acute conversion symptoms and 57
      age- and sex-matched healthy controls, during a resting condition and then during
      tasks involving cognitive and emotional activation. Arousal and autonomic
      regulation were assessed by measures of heart rate and heart rate variability.
      Psychological measures included attachment and emotional distress. RESULTS:
      Children and adolescents with conversion symptoms displayed higher autonomic
      arousal than did the controls, both at baseline and during task conditions
      (higher heart rate: baseline mean [standard deviation] = 82 [9.49] versus 74
      [10.79] beats/min, p < .001; lower root mean squared successive differences-heart
      rate variability: 45.35 [27.97] versus 58.62 [25.69] ms(2), p = .012; and lower
      high-frequency heart rate variability: 6.50 [1.19] versus 7.01 [0.95] ln[ms(2)] p
      = .017), and decreased autonomic regulation (attenuation of heart rate increases
      across tasks). The baseline pattern of increased autonomic arousal was especially
      pronounced in children with coercive-preoccupied patterns of attachment.
      Autonomic measures were not correlated with measures of emotional distress.
      CONCLUSIONS: High autonomic arousal may be a precondition for generating
      conversion symptoms. Functional dysregulations of the cardiac, respiratory, and
      circulatory systems may mediate fainting episodes and nonepileptic seizures, and
      aberrant patterns of functional connectivity between motor areas and central
      arousal systems may be responsible for generating motor conversion symptoms.

PMID- 25954918
TI  - Synthesis and structural characterisation of amides from picolinic acid and
      pyridine-2,6-dicarboxylic acid.
AB  - Coupling picolinic acid (pyridine-2-carboxylic acid) and pyridine-2,6
      dicarboxylic acid with N-alkylanilines affords a range of mono- and bis-amides in
      good to moderate yields. These amides are of interest for potential applications
      in catalysis, coordination chemistry and molecular devices. The reaction of
      picolinic acid with thionyl chloride to generate the acid chloride in situ leads
      not only to the N-alkyl-N-phenylpicolinamides as expected but also the
      corresponding 4-chloro-N-alkyl-N-phenylpicolinamides in the one pot. The two
      products are readily separated by column chromatography. Chlorinated products are
      not observed from the corresponding reactions of pyridine-2,6-dicarboxylic acid.
      X-Ray crystal structures for six of these compounds are described. These
      structures reveal a general preference for cis amide geometry in which the
      aromatic groups (N-phenyl and pyridyl) are cis to each other and the pyridine
      nitrogen anti to the carbonyl oxygen. Variable temperature 1H NMR experiments
      provide a window on amide bond isomerisation in solution. 

PMID- 25954920
TI  - Development and integration of block operations for data invariant automation of
      digital preprocessing and analysis of biological and biomedical Raman spectra.
AB  - High-throughput information extraction from large numbers of Raman spectra is
      becoming an increasingly taxing problem due to the proliferation of new
      applications enabled using advances in instrumentation. Fortunately, in many of
      these applications, the entire process can be automated, yielding reproducibly
      good results with significant time and cost savings. Information extraction
      consists of two stages, preprocessing and analysis. We focus here on the
      preprocessing stage, which typically involves several steps, such as calibration,
      background subtraction, baseline flattening, artifact removal, smoothing, and so
      on, before the resulting spectra can be further analyzed. Because the results of
      some of these steps can affect the performance of subsequent ones, attention must
      be given to the sequencing of steps, the compatibility of these sequences, and
      the propensity of each step to generate spectral distortions. We outline here
      important considerations to effect full automation of Raman spectral
      preprocessing: what is considered full automation; putative general principles to
      effect full automation; the proper sequencing of processing and analysis steps;
      conflicts and circularities arising from sequencing; and the need for, and
      approaches to, preprocessing quality control. These considerations are discussed
      and illustrated with biological and biomedical examples reflecting both
      successful and faulty preprocessing. 

PMID- 25954917
TI  - Chronic inflammation and cancer: emerging roles of triggering receptors expressed
      on myeloid cells.
AB  - Inflammation is tightly regulated by a vast system that is intricately
      interconnected with innate immunity. Aberrations in expression or signaling, such
      as in innate immune receptors, can create excessive inflammation and, when
      chronic, often promote oncogenesis. The triggering receptor expressed on myeloid
      cells receptor family has been characterized as a major player in the
      amplification and signaling of the inflammatory response. In a number of chronic
      inflammatory conditions and malignancies, the triggering receptor expressed on
      myeloid cells has been implicated in disease severity and progression. In this
      article, the current understanding of triggering receptor expressed on myeloid
      cells function in pre-malignant, malignant and chronic inflammatory conditions is
      critically reviewed. The potential for therapeutic application is also discussed.

PMID- 25954921
TI  - Retraction: "Total Hip Arthroplasty With Acetabular Fixation: An Unexpected
      Complication".

PMID- 25954922
TI  - Insights into mechanisms of capillary assembly.
AB  - Capillary assembly in a topographical template is a powerful and flexible method
      for fabricating complex and programmable particle assemblies. To date, very
      little attention has been paid to the effects that the trap geometry--in
      particular the trap depth--has on the outcome of the assembly process. In this
      paper, we provide insights into the mechanisms behind this directed assembly
      method by systematically studying the impact of the trap depth and the surface
      tension of the suspension. Using confocal microscopy, we investigate the assembly
      process at the single-particle level and use these observations to formulate a
      simple mechanical model that offers guidelines for the successful assembly of
      single or multiple particles in a trap. In particular, single particles are
      assembled for shallow traps and moderate surface tensions, opening up the
      possibility to fabricate multifunctional particle dimers in two consecutive
      assembly steps.

PMID- 25954924
TI  - Spectrometric imaging of polarization colors and its application in forensic
      fiber analysis.
AB  - A hyperspectral imaging instrument analyzing fibers between crossed polarizers
      spectrometrically is presented. The principle of operation is introduced and
      illustrated briefly by the theory of polarization and birefingence and
      calculations based on Stokes parameters and Muller matrices. Afterward, the
      developed instrumentation and results are detailed. Results obtained by the
      calculations and developed instrumentation indicate that the retardance of
      birefringent materials can be calculated over a high range and with a high
      accuracy. In addition, the spatial resolution of the instrument suffices to
      analyze different regions within a fiber individually. This allows the selection
      of a region at the center of an analyzed fiber that is shown to provide an
      optimal signal. The developed software enables analysis of the polarization color
      and the "normal", i.e., absorptive color of the sample individually. These
      features make possible a preliminary identification of fibers, without isolation
      of the fiber from a microscope slide. The instrument forms a powerful new
      approach to automated analyses in forensic fiber evidence, as it can establish
      analyses of morphology, color, and identity of a set of samples in a high
      throughput, automated, and objective way. 

PMID- 25954923
TI  - Functional protease profiling for laboratory based diagnosis of invasive
      aspergillosis.
AB  - Invasive aspergillosis (IA) remains difficult to diagnose in immunocompromised
      patients, because diagnostic criteria according to EORTC/MSG guidelines are often
      not met and have low sensitivity. Hence there is an urgent need to improve
      diagnostic procedures by developing novel approaches. In the present study, we
      present a proof of concept experiment for the monitoring of Aspergillus
      associated protease activity in serum specimens for diagnostic purpose. Synthetic
      peptides that are selectively cleaved by proteases secreted from Aspergillus
      species were selected from our own experiments and published data. These so
      called reporter peptides (RP, n=5) were added to serum specimens from healthy
      controls (HC, n=101) and patients with proven (IA, n=9) and possible (PIA, n=144)
      invasive aspergillosis. Spiked samples were incubated ex vivo under strictly
      standardized conditions. Proteolytic fragments were analyzed using MALDI-TOF mass
      spectrometry. Spiked specimens of IA patients had highest concentrations of RP
      fragments followed by PIA and HC. The median signal intensity was 116.546 (SD,
      53.063) for IA and 5.009 (SD, 8.432) for HC. A cut-off >36.910 was chosen that
      performed with 100% specificity and sensitivity. Patients with PIA had either
      values above [53% (76/144)] or below [47% (67/144)] this chosen cut-off. The
      detection of respective reporter peptide fragments can easily be performed by
      MALDI TOF mass spectrometry. In this proof of concept study we were able to
      demonstrate that serum specimens of patients with IA have increased proteolytic
      activity towards selected reporter peptides. However, the diagnostic value of
      functional protease profiling has to be validated in further prospective studies.
      It is likely that a combination of existing and new methods will be required to
      achieve optimal performance for diagnosis of IA in the future.

PMID- 25954925
TI  - Role of alpha-synuclein in cognitive dysfunction: Studies in Drosophila
      melanogaster.
AB  - alpha-Synuclein (alpha-Syn) is hypothesized to have a critical role in sporadic
      and genetic cases of Parkinson's disease (PD) in which Lewy bodies, as the
      hallmark of PD, are formed from abnormal aggregates of alpha-Syn. To determine
      the role of alpha-Syn in the motor and cognitive dysfunction observed in PD, a
      Drosophila melanogaster model was established to investigate the
      electrophysiological and ethological changes caused by overexpression of alpha
      Syn. The present data indicated that alpha-Syn overexpression reduced the
      synaptic transmission of cholinergic neurons by modulating the calcium channel
      currents in the projection neurons in the antennal lobe region of the Drosophila
      brain, as well as the learning and memory ability of the flies. However, the
      locomotor ability of the Drosophila remained unaffected. The present findings
      suggested that alpha-Syn may be associated with senile dementia in patients with
      PD.

PMID- 25954926
TI  - Toll-like receptor 2 and -4 are involved in the pathogenesis of the Guillain
      Barre syndrome.
AB  - Guillain-Barre syndrome (GBS) is an autoimmune disorder of the peripheral nervous
      system characterized by weakness in the limbs. To date, numerous hypotheses have
      been suggested to explain the pathogenesis of GBS; however, the pathogenesis of
      GBS remains to be elucidated. The aim of the present study was to investigate the
      association between Toll-like receptor (TLR) 2, TLR4 and GBS. Therefore, the mRNA
      of TLR2, TLR4, myeloid differentiation factor (MyD)88 and nuclear factor (NF)
      kappaB of peripheral blood mononuclear cells (PBMCs) in patients with GBS and
      healthy controls was assessed. To confirm the function of TLR2 and TLR4 in the
      pathogenesis of GBS, PBMCs derived from patients with GBS and healthy controls
      were cultured with various TLR agonists. The levels of tumor necrosis factor
      (TNF)-alpha and interleukin (IL)-1beta were measured in the culture supernatant
      and fasting serum was obtained for the detection of anti-ganglioside antibodies.
      The results revealed that the mRNA levels of TLR2, TLR4, MyD88 and NF-kappaB were
      significantly increased in patients with GBS compared with those in healthy
      controls (P=0.003, 0.017, 0.032 and 0.015, respectively). PBMCs from patients
      with GBS secreted higher levels of TNF-alpha and IL-1beta than those from control
      subjects. The positive rate of immunoglobulin (Ig)G and IgM anti-ganglioside
      antibodies in patients with severe GBS was 42.86%, which was markedly higher than
      rates found in patients with mild GBS (9.09 and 18.18%, respectively). The
      results of the present study demonstrated that TLR2 and TLR4 are involved in the
      pathogenesis of GBS and that they and their associated signaling pathways may be
      targets for the treatment of GBS.

PMID- 25954927
TI  - Number and distribution of myofibroblasts and alpha-smooth muscle actin
      expression levels in fetal membranes with and without gestational complications.
AB  - The permeability and tension of fetal membranes (FMs) is associated with
      extracellular matrix proteins produced largely by myofibroblasts (MFBBs). alpha
      smooth muscle actin (alpha-SMA) is involved in the contraction of MFBBs and has
      been implicated as a special biomarker of MFBBs in non-vessel FM. The present
      study demonstrated, by using immunohistochemistry, reverse-transcription
      polymerase chain reaction and western blotting, that MFBBs were mainly
      distributed in chorioamniotic mesoderm at 16-21 weeks and in chorionic mesoderm
      at 22-40 weeks, respectively, while overlapping with each other at 16-40 weeks.
      In addition, a quantity of MFBBs were identified in chorionic epithelia at 16-40
      weeks. The MFBBs were distributed parallel to the FMs. The quantities of MFBBs
      and the expression levels of alpha-SMA were negatively associated with increasing
      gestational progress and of amniotic fluid indexes in full-term females (those
      from oligohydramnios were higher than polyhydramnios); however, the thickness of
      the FM's mesoderm remained unchanged. Of note, the number of MFBBs in early-onset
      severe pre-eclampsia (EOSP) was significantly decreased in comparison with that
      in EOSP controls and late-onset severe pre-eclampsia (LOSP), while that in LOSP
      was higher than that in LOSP controls. The present data indicated that the
      changes in the quantity and distribution of MFBBs in the FM affects the
      permeability and tension of the FM. In addition, the findings suggested that the
      expression levels of alpha-SMA in the FM also contributed to the properties of
      the FM. Simultaneously, the number and distribution of MFBBs and the expression
      levels of alpha-SMA in the FM may be involved in the mechanisms of development,
      apoptosis and trophoblast-MFBB transformation of the FM.

PMID- 25954928
TI  - MicroRNA-153 functions as a tumor suppressor by targeting SET7 and ZEB2 in
      ovarian cancer cells.
AB  - The overall goal of the present study was to find and validate unidentified
      miRNAs that regulate epithelial-mesenchymal transition (EMT) and proliferation in
      ovarian cancer. Furthermore, we demonstrate that the high expression of miR-153
      in human epithelial ovarian cancer (EOC) is associated with better survival. The
      mean expression level of miR-153 in ovarian cancer was significantly lower than
      in the adjacent carcinoma tissue. In the present study, we report that miR-153
      are negative regulators of SET7 and ZEB2, miR-153 regulates SET7/ZEB2 expression
      and promotes SET7/ZEB2 mRNA degradation. Further, confirmed by reporter assays,
      SET7/ZEB2 are downstream targets of miR-153 directly bound to the 3' untranslated
      region (3'-UTR). Clone formation and wound-healing assay as well as Transwell
      assay proved that silencing of SET7 or ZEB2 partially abolished the enhancement
      of cell proliferation and invasion induced by downregulated miR-153. SET7 and
      ZEB2 are negatively correlated with miR-153 expression in human ovarian cancer
      and indicated a worse survival. Considering the role of SET7 and ZEB2 in EOC, it
      is important to clarify how the expression of SET7 and ZEB2 are regulated. Based
      on our results miR-153 inhibits proliferation and suppresses EMT and the invasive
      potential of ovarian cancer cells through downregulation of SET7 and ZEB2,
      supporting the pursuit of miR-153 as a potential target for ovarian cancer
      intervention. 

PMID- 25954929
TI  - Potassium aspartate inhibits SH-SY5Y cell damage and apoptosis induced by ouabain
      and H2O2.
AB  - The present study aimed to investigate the effects of L-aspartic acid potassium
      salt (potassium aspartate, K-asp) on SH-SY5Y cells treated with ouabain and H2O2.
      An 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was
      performed to investigate the effects of K-asp on SH-SY5Y cell death induced by
      ouabain. Nissl staining was used to demonstrate the morphological changes of the
      SH-SY5Y cells. Light microscopy and 4',6-diamidino-2-phenylindole (DAPI) staining
      were performed to visualize apoptosis in SH-SY5Y cells incubated with ouabain for
      6, 24 and 48 h. Transmission electron microscopy was used to observe the effect
      of K-asp on ultrastructural changes of the SH-SY5Y cells following incubation
      with ouabain for 24 and 48 h. An annexin V-fluorescein isothiocyanate/propidium
      binding assay and flow cytometry were performed successively to investigate how K
      asp affected the H2O2-induced cell apoptosis. The MTT assay demonstrated that K
      asp attenuated the cytotoxicity of the SH-SY5Y cells following treatment with
      ouabain, in a dose-dependent manner. The cell survival rates following 48 h
      incubation in the K-asp (15 mM) and K-asp (25 mM) groups were higher compared
      with the KCl and MK801 groups. Nissl staining demonstrated that the severity of
      cell injury in the KCl and K-asp (25 mM) groups were alleviated. In the DAPI
      staining and transmission electron microscopy analyses, KCl and K-asp (25 mM)
      reduced the rate of ouabain-induced apoptosis. Flow cytometry revealed that K-asp
      (25 mM) reduced H2O2 -induced apoptosis. These results demonstrated that K-asp
      (25 mM) inhibited the ouabain and H2O2-induced SH-SY5Y cell damage and apoptosis,
      possibly by supplementing levels of intracellular K(+).

PMID- 25954930
TI  - Modelling the Effects of Electrical Coupling between Unmyelinated Axons of
      Brainstem Neurons Controlling Rhythmic Activity.
AB  - Gap junctions between fine unmyelinated axons can electrically couple groups of
      brain neurons to synchronise firing and contribute to rhythmic activity. To
      explore the distribution and significance of electrical coupling, we modelled a
      well analysed, small population of brainstem neurons which drive swimming in
      young frog tadpoles. A passive network of 30 multicompartmental neurons with
      unmyelinated axons was used to infer that: axon-axon gap junctions close to the
      soma gave the best match to experimentally measured coupling coefficients; axon
      diameter had a strong influence on coupling; most neurons were coupled indirectly
      via the axons of other neurons. When active channels were added, gap junctions
      could make action potential propagation along the thin axons unreliable.
      Increased sodium and decreased potassium channel densities in the initial axon
      segment improved action potential propagation. Modelling suggested that the
      single spike firing to step current injection observed in whole-cell recordings
      is not a cellular property but a dynamic consequence of shunting resulting from
      electrical coupling. Without electrical coupling, firing of the population during
      depolarising current was unsynchronised; with coupling, the population showed
      synchronous recruitment and rhythmic firing. When activated instead by increasing
      levels of modelled sensory pathway input, the population without electrical
      coupling was recruited incrementally to unpatterned activity. However, when
      coupled, the population was recruited all-or-none at threshold into a rhythmic
      swimming pattern: the tadpole "decided" to swim. Modelling emphasises
      uncertainties about fine unmyelinated axon physiology but, when informed by
      biological data, makes general predictions about gap junctions: locations close
      to the soma; relatively small numbers; many indirect connections between neurons;
      cause of action potential propagation failure in fine axons; misleading
      alteration of intrinsic firing properties. Modelling also indicates that
      electrical coupling within a population can synchronize recruitment of neurons
      and their pacemaker firing during rhythmic activity. 

PMID- 25954932
TI  - Correction: Mitotic-Chromosome-Based Physical Mapping of the Culex
      quinquefasciatus Genome.

PMID- 25954931
TI  - Mechanisms of Intestinal Serotonin Transporter (SERT) Upregulation by TGF-beta1
      Induced Non-Smad Pathways.
AB  - TGF-beta1 is an important multifunctional cytokine with numerous protective
      effects on intestinal mucosa. The influence of TGF-beta1 on serotonin transporter
      (SERT) activity, the critical mechanism regulating the extracellular availability
      of serotonin (5-HT), is not known. Current studies were designed to examine acute
      effects of TGF-beta1 on SERT. Model human intestinal Caco-2 cells grown as
      monolayer's or as cysts in 3D culture and ex vivo mouse model were utilized.
      Treatment of Caco-2 cells with TGF-beta1 (10 ng/ml, 60 min) stimulated SERT
      activity (~2 fold, P<0.005). This stimulation of SERT function was dependent upon
      activation of TGF-beta1 receptor (TGFRI) as SB-431542, a specific TGF-betaRI
      inhibitor blocked the SERT stimulation. SERT activation in response to TGF-beta1
      was attenuated by inhibition of PI3K and occurred via enhanced recruitment of
      SERT-GFP to apical surface in a PI3K dependent manner. The exocytosis inhibitor
      brefeldin A (2.5 MUM) attenuated the TGF-beta1-mediated increase in SERT
      function. TGF-beta1 increased the association of SERT with the soluble N
      ethylmaleimide-sensitive factor attachment protein receptor (SNARE) syntaxin 3
      (STX3) and promoted exocytosis of SERT. Caco-2 cells grown as cysts in 3D culture
      recapitulated the effects of TGF-beta1 showing increased luminal staining of
      SERT. Ussing chamber studies revealed increase in 3H-5-HT uptake in mouse ileum
      treated ex vivo with TGF-beta1 (10 ng/ml, 1h). These data demonstrate a novel
      mechanism rapidly regulating intestinal SERT via PI3K and STX3. Since decreased
      SERT is implicated in various gastro-intestinal disorders e.g IBD, IBS and
      diarrhea, understanding mechanisms stimulating SERT function by TGF-beta1 offers
      a novel therapeutic strategy to treat GI disorders. 

PMID- 25954933
TI  - Correction: Cognitive demands of Lower Paleolithic toolmaking.

PMID- 25954935
TI  - Age of onset in social anxiety disorder: Relation to clinical variables and major
      depression comorbidity.
AB  - BACKGROUND: The aim of this study was to determine the rates of early- and late
      onset social anxiety disorder (SAD) and to investigate the effects of onset time
      on clinical characteristics and the course of SAD. METHODS: A total of 377
      patients with SAD were assessed using a sociodemographic data form, the Liebowitz
      Social Anxiety Scale (LSAS), Beck Depression Inventory (BDI), and the Global
      Assessment of Functioning (GAF). Three hundred patients with SAD onset before age
      18 were classified as members of the early-onset group, whereas 77 patients with
      SAD onset at age >= 18 comprised the late-onset group. The 2 groups were compared
      in terms of sociodemographic and clinical characteristics, comorbidity, and scale
      scores. RESULTS: The rate of SAD onset before age 18 was 79.6%. Compared with the
      late-onset group, the early-onset group had a younger age at first depressive
      episode, higher rate of atypical depression, higher LSAS and BDI scores, and
      lower GAF scores. CONCLUSIONS: In cases of early onset of SAD, symptom severity
      of both SAD and comorbid depression increased and functionality decreased. It is
      important to assess and treat SAD patients at a younger age because early-onset
      SAD may be associated with a more severe course and higher rate of major
      depression comorbidity.

PMID- 25954937
TI  - Psychiatric disorder-weight associations and the moderating effect of sex in an
      outpatient psychiatric sample.
AB  - BACKGROUND: Few studies have examined the association between weight and
      psychiatric disorders in psychiatric treatment samples, and no known studies in
      treatment samples have examined potential moderators of the psychiatric illness
      weight relationship. The aim of the present study is to examine if weight is
      associated with specific mood and anxiety disorders in a psychiatric treatment
      seeking sample, and if a person's sex moderate any of these associations. Greater
      knowledge of particular subgroups experiencing psychiatric illness-obesity
      comorbidity could aid in better providing personalized treatment. METHODS:
      Participants (N = 3,585) were administered a semi-structured diagnostic interview
      at initial presentation for treatment. Hierarchical logistic regression analyses
      examined simple effects of body mass index (BMI) and sex on current mood and
      anxiety disorders and the moderating effects of sex. RESULTS: We did not find
      simple effects between BMI and mood/anxiety disorders after controlling for
      demographic variables. Female sex moderated a relationship between BMI and social
      anxiety disorder (SAD) only. CONCLUSIONS: Findings suggest that the presence of
      SAD in psychiatric patients is associated with a higher BMI only for females, yet
      this was not the case for the presence of other mood and anxiety disorders.
      Further research examining the relationship between SAD, weight, and sex is
      warranted.

PMID- 25954936
TI  - College students with depressive symptoms with and without fatigue: Differences
      in functioning, suicidality, anxiety, and depressive severity.
AB  - BACKGROUND: We examined whether fatigue was associated with greater symptomatic
      burden and functional impairment in college students with depressive symptoms.
      METHODS: Using data from the self-report Beck Depression Inventory (BDI), we
      stratified a group of 287 students endorsing significant symptoms of depression
      (BDI score >= 13) into 3 levels: no fatigue, mild fatigue, or moderate/severe
      fatigue. We then compared the 3 levels of fatigue across a battery of psychiatric
      and functional outcome measures. RESULTS: Approximately 87% of students endorsed
      at least mild fatigue. Students with moderate/severe fatigue had significantly
      greater depressive symptom severity compared with those with mild or no fatigue
      and scored higher on a suicide risk measure than those with mild fatigue.
      Students with severe fatigue evidenced greater frequency and intensity of anxiety
      than those with mild or no fatigue. Reported cognitive and functional impairment
      increased significantly as fatigue worsened. CONCLUSIONS: Depressed college
      students with symptoms of fatigue demonstrated functional impairment and
      symptomatic burden that worsened with increasing levels of fatigue. Assessing and
      treating symptoms of fatigue appears warranted within this population.

PMID- 25954939
TI  - Meningioma and psychiatric symptoms: A case report and brief review.
AB  - BACKGROUND: Atypical presentation of psychiatric symptoms can lead to a variety
      of misdiagnoses. Organic causes, including brain tumors, should be considered
      under these circumstances. METHODS: We present a case report of an 84-year-old
      woman with irritable, aggressive, and delusional behavior. Her earlier diagnoses
      included altered mental status, encephalopathy, dementia, nonspecified psychosis,
      and delirium with delusions. We suspected that a brain tumor could be causing her
      psychiatric symptoms. RESULTS: CT of the head revealed 2 calcified meningiomas,
      which did not require surgery. Neuropsychological testing results were consistent
      with frontal lesion type of cognitive and psychotic symptoms. Psychiatric
      symptoms improved with risperidone. A brief review of the literature is included.
      CONCLUSIONS: Brain imaging should be considered in cases of atypical psychiatric
      presentations. Past medical records and neuropsychological testing could assist
      in the diagnosis.

PMID- 25954938
TI  - Similar changes in cognitions following cognitive-behavioral therapy or
      escitalopram for major depressive disorder: Implications for mechanisms of
      change.
AB  - BACKGROUND: Psychosocial treatments and medications both have been shown to be
      effective in treating major depressive disorder. We hypothesized that cognitive
      behavioral therapy (CBT) would outperform medication on measures of cognitive
      change. METHODS: We randomized depressed individuals to 12 weeks of CBT (n = 15)
      or escitalopram (n = 11). In an intent-to-treat analysis (n = 26), we conducted a
      repeated measures analysis of variance to examine changes in depressive symptoms
      (ie, 17-item Hamilton Depression Rating Scale, Beck Depression Inventory),
      anhedonia (ie, Snaith-Hamilton Pleasure Scale), cognitive measures (ie,
      Dysfunctional Attitudes Scale, Automatic Thoughts Questionnaire, Perceived Stress
      Scale), and quality of life (ie, Quality of Life Enjoyment and Satisfaction
      Questionnaire) at 4 time points: baseline, week 4, week 8, and week 12. Treatment
      for both groups started at baseline, and patients received either 12 weeks of
      individual CBT or 12 weeks of escitalopram with flexible dosing (10 to 20 mg).
      RESULTS: Collapsing the escitalopram and CBT groups, there were statistically
      significant pre-post changes on all outcome measures. However, there were no
      statistically significant differences between treatment groups on any of the
      outcome measures, including cognitive measures across time points. CONCLUSIONS:
      Our results suggest that both CBT and escitalopram have similar effects across a
      variety of domains and that, in contrast to our a priori hypothesis, CBT and
      escitalopram were associated with comparable changes on cognitive measures.

PMID- 25954940
TI  - The relationship between cannabidiol and psychosis: A review.
AB  - BACKGROUND: Cannabis sativa is the most widely used illicit drug in the world.
      There is concern about its harmful effects, especially because of increasing
      potency, which has been reported globally. These effects seem to result from the
      relationship among its components, notably delta-9-tetrahydrocannabinol (THC) and
      cannabidiol (CBD), which have opposite effects. THC is considered responsible for
      the main psychotropic effects of the drug, while CBD seems to antagonize these
      effects, particularly those that induce psychosis. METHODS: We performed a PubMed
      literature review of research discussing the association of cannabidiol and
      psychosis published from 2006 to July 2014. RESULTS: The effects of Cannabis seem
      to depend on several variables related to the type of plant, its strength, usage
      patterns, and intersubjective variations. CBD could be used to treat several
      conditions, including psychosis, when the current treatment is associated with
      significant side effects. CONCLUSIONS: Because of the complexity of the subject,
      including limitations and contradictions in studies available to date, further
      research involving the possible antipsychotic effect and other potential positive
      effects of Cannabis are needed. There also are noteworthy differences between the
      research design parameters and recreational use of Cannabis.

PMID- 25954941
TI  - Canadian Network for Mood and Anxiety Treatments (CANMAT) consensus
      recommendations for functional outcomes in major depressive disorder.
AB  - BACKGROUND: Functional recovery is increasingly recognized as a priority in the
      treatment of major depressive disorder (MDD), by both clinicians and patients.
      However, symptom improvement remains the focus of traditional clinical trials for
      MDD and of the regulatory approval process for new medications and other
      interventions. Many studies have shown that functional outcomes do not always
      correspond to symptom-based outcomes. METHODS: Representatives from clinical
      practice, professional societies, academia, industry, and government were invited
      by the Canadian Network for Mood and Anxiety Treatments to develop
      recommendations for the conceptualization and measurement of functional outcomes
      in clinical trials of MDD. RESULTS: Definitions and conceptual frameworks to
      guide assessment of functioning are described, as well as research methodology
      applicable to the broad spectrum of treatments for MDD. Examples are given for
      validated instruments, including patient-reported outcome measures. Strategies
      for knowledge translation and dissemination are suggested and consensus
      recommendations summarized. CONCLUSIONS: As the societal burden and financial
      costs of MDD continue to escalate, so does the need for evidence-based and cost
      effective interventions that demonstrate improvement in functioning. Routine
      assessment of functional outcomes will benefit not only individuals with MDD but
      also diverse stakeholders concerned about the efficacy and cost-effectiveness of
      interventions.

PMID- 25954942
TI  - Vitamin D and neurocognitive disorder due to Alzheimer's disease: A review of the
      literature.
AB  - BACKGROUND: According to the Alzheimer's Disease 2014 Facts and Figures report,
      an estimated 5 million older Americans are living with Alzheimer's disease (AD).
      AD is the sixth leading cause of death in the United States and the only 1 among
      the top 10 that cannot be prevented, cured, or even slowed. Predictably, AD puts
      an enormous cost burden on the U.S. health care system, with costs expected to
      soar to $1.2 trillion in 2050. Many individuals with minor cognitive impairment
      do not seek treatment and/or delay treatment until perceptible deficits
      indicative of moderate stage of disease are present. Several new drugs for AD are
      under development based on etiological disease theories, but their long-term
      impact on cognition and/or function is unclear. One potential treatment is to
      address low serum 25-hydroxy vitamin D (25[OH]D). METHODS: We performed a
      literature review on the topic of low vitamin D levels and cognition in geriatric
      patients. RESULTS: Recent studies have associated low vitamin D levels with
      cognitive complaints, impairment, and AD in geriatric patients; however, there is
      a dearth of prospective studies on the topic. CONCLUSIONS: Available data suggest
      that more research is needed to promote a better understanding of vitamin D
      levels and incident AD.

PMID- 25954943
TI  - An Analysis of Artificial Reef Fish Community Structure along the Northwestern
      Gulf of Mexico Shelf: Potential Impacts of "Rigs-to-Reefs" Programs.
AB  - Artificial structures are the dominant complex marine habitat type along the
      northwestern Gulf of Mexico (GOM) shelf. These habitats can consist of a variety
      of materials, but in this region are primarily comprised of active and reefed oil
      and gas platforms. Despite being established for several decades, the fish
      communities inhabiting these structures remain poorly investigated. Between 2012
      and 2013 we assessed fish communities at 15 sites using remotely operated
      vehicles (ROVs). Fish assemblages were quantified from standing platforms and an
      array of artificial reef types (Liberty Ships and partially removed or toppled
      platforms) distributed over the Texas continental shelf. The depth gradient
      covered by the surveys (30-84 m) and variability in structure density and relief
      also permitted analyses of the effects of these characteristics on fish richness,
      diversity, and assemblage composition. ROVs captured a variety of species
      inhabiting these reefs from large transient piscivores to small herbivorous reef
      fishes. While structure type and relief were shown to influence species richness
      and community structure, major trends in species composition were largely
      explained by the bottom depth where these structures occurred. We observed a
      shift in fish communities and relatively high diversity at approximately 60 m
      bottom depth, confirming trends observed in previous studies of standing
      platforms. This depth was also correlated with some of the largest Red Snapper
      captured on supplementary vertical longline surveys. Our work indicates that
      managers of artificial reefing programs (e.g., Rigs-to-Reefs) in the GOM should
      carefully consider the ambient environmental conditions when designing reef
      sites. For the Texas continental shelf, reefing materials at a 50-60 m bottom
      depth can serve a dual purpose of enhancing diving experiences and providing the
      best potential habitat for relatively large Red Snapper. 

PMID- 25954944
TI  - Regulation of OsmiR156h through Alternative Polyadenylation Improves Grain Yield
      in Rice.
AB  - Substantial increases in grain yield of cereal crops are required to feed a
      growing human population. Here we show that a natural variant of SEMIDWARF AND
      HIGH-TILLERING (SDT) increases harvest index and grain productivity in rice. Gain
      of-function sdt mutation has a shortened polyadenylation tail on the OsmiR156h
      microRNA precursor, which cause the up-regulation of OsmiR156h. The plants
      carrying the semidominant sdt allele exhibit reduced plant height, enhanced
      lodging resistance, increased tiller numbers per plant, and resulting in an
      increased grain yield. We also show that combining the sdt allele with the
      OsSPL14WFP allele can be effective in simultaneously improving tillering capacity
      and panicle branching, thereby leading to higher harvest index and grain yield.
      Most importantly, pyramiding of the sdt allele and the green revolution gene sd1
      enhances grain yield by about 20% in hybrid rice breeding. Our results suggest
      that the manipulation of the polyadenylation status of OsmiR156 represents a
      novel strategy for improving the yield potential of rice over what is currently
      achievable. 

PMID- 25954945
TI  - Delphinidin induces cytotoxicity and potentiates cytocidal effect in combination
      with arsenite in an acute promyelocytic leukemia NB4 cell line.
AB  - The effects of delphinidin were investigated by focusing on growth inhibition,
      cell cycle arrest and apoptosis induction in the human acute promyelocytic
      leukemia (APL) NB4 cell line. Delphinidin exhibited a dose- and time-dependent
      cytotoxic effect against NB4 cells. Almost no cell cycle arrest, but an apparent
      increase in the percentage of sub-G1 cells was observed in delphinidin-treated
      cells. The activation of caspase-8 and -9 was observed as early as 1-h post
      exposure to delphinidin, followed by the activation of caspase-3 from 3-h post
      exposure. A substantial decrease in the expression level of Bid was also observed
      as early as 1-h post-exposure. A modest decrease in the mitochondrial membrane
      potential (DeltaPsim) was observed at 3-h post-exposure, followed by a
      substantial time-dependent decrease in DeltaPsim in treated cells. Delphinidin
      exerted more potent cytotoxicity against NB4 cells than normal peripheral blood
      mononuclear cells (PBMNCs). In addition, delphinidin in combination with an
      arsenic derivative arsenite (As(III)), which has demonstrated marked efficacy in
      patients with APL, achieved an enhanced cytocidal effect against NB4 cells, but
      lesser on PBMNCs. Treatment of NB4 cells with As(III) plus delphinidin did not
      increase, but decreased slightly, intracellular arsenic accumulation (As[i]) as
      compared to that treated with As(III) alone. These results suggested that
      delphinidin selectively sensitized NB4 cells to As(III), resulting in the
      enhancement of As(III) cytotoxicity by strengthening intrinsic/extrinsic pathway
      mediated apoptosis induction, rather than affecting the As[i] levels. These
      observations may offer a rationale for the use of delphinidin to improve the
      clinical efficacy of As(III).

PMID- 25954947
TI  - Nonlinear spike-and-slab sparse coding for interpretable image encoding.
AB  - Sparse coding is a popular approach to model natural images but has faced two
      main challenges: modelling low-level image components (such as edge-like
      structures and their occlusions) and modelling varying pixel intensities.
      Traditionally, images are modelled as a sparse linear superposition of dictionary
      elements, where the probabilistic view of this problem is that the coefficients
      follow a Laplace or Cauchy prior distribution. We propose a novel model that
      instead uses a spike-and-slab prior and nonlinear combination of components. With
      the prior, our model can easily represent exact zeros for e.g. the absence of an
      image component, such as an edge, and a distribution over non-zero pixel
      intensities. With the nonlinearity (the nonlinear max combination rule), the idea
      is to target occlusions; dictionary elements correspond to image components that
      can occlude each other. There are major consequences of the model assumptions
      made by both (non)linear approaches, thus the main goal of this paper is to
      isolate and highlight differences between them. Parameter optimization is
      analytically and computationally intractable in our model, thus as a main
      contribution we design an exact Gibbs sampler for efficient inference which we
      can apply to higher dimensional data using latent variable preselection. Results
      on natural and artificial occlusion-rich data with controlled forms of sparse
      structure show that our model can extract a sparse set of edge-like components
      that closely match the generating process, which we refer to as interpretable
      components. Furthermore, the sparseness of the solution closely follows the
      ground-truth number of components/edges in the images. The linear model did not
      learn such edge-like components with any level of sparsity. This suggests that
      our model can adaptively well-approximate and characterize the meaningful
      generation process. 

PMID- 25954946
TI  - Computational Aerodynamic Analysis of a Micro-CT Based Bio-Realistic Fruit Fly
      Wing.
AB  - The aerodynamic features of a bio-realistic 3D fruit fly wing in steady state
      (snapshot) flight conditions were analyzed numerically. The wing geometry was
      created from high resolution micro-computed tomography (micro-CT) of the fruit
      fly Drosophila virilis. Computational fluid dynamics (CFD) analyses of the wing
      were conducted at ultra-low Reynolds numbers ranging from 71 to 200, and at
      angles of attack ranging from -10 degrees  to +30 degrees . It was found that in
      the 3D bio-realistic model, the corrugations of the wing created localized
      circulation regions in the flow field, most notably at higher angles of attack
      near the wing tip. Analyses of a simplified flat wing geometry showed higher lift
      to drag performance values for any given angle of attack at these Reynolds
      numbers, though very similar performance is noted at -10 degrees . Results have
      indicated that the simplified flat wing can successfully be used to approximate
      high-level properties such as aerodynamic coefficients and overall performance
      trends as well as large flow-field structures. However, local pressure peaks and
      near-wing flow features induced by the corrugations are unable to be replicated
      by the simple wing. We therefore recommend that accurate 3D bio-realistic
      geometries be used when modelling insect wings where such information is useful.

PMID- 25954948
TI  - Collaborative Localization and Location Verification in WSNs.
AB  - Localization is one of the most important technologies in wireless sensor
      networks. A lightweight distributed node localization scheme is proposed by
      considering the limited computational capacity of WSNs. The proposed scheme
      introduces the virtual force model to determine the location by incremental
      refinement. Aiming at solving the drifting problem and malicious anchor problem,
      a location verification algorithm based on the virtual force mode is presented.
      In addition, an anchor promotion algorithm using the localization reliability
      model is proposed to re-locate the drifted nodes. Extended simulation experiments
      indicate that the localization algorithm has relatively high precision and the
      location verification algorithm has relatively high accuracy. The communication
      overhead of these algorithms is relative low, and the whole set of reliable
      localization methods is practical as well as comprehensive. 

PMID- 25954949
TI  - Intelligent simultaneous quantitative online analysis of environmental trace
      heavy metals with total-reflection X-ray fluorescence.
AB  - Total-reflection X-ray fluorescence (TXRF) has achieved remarkable success with
      the advantages of simultaneous multi-element analysis capability, decreased
      background noise, no matrix effects, wide dynamic range, ease of operation, and
      potential of trace analysis. Simultaneous quantitative online analysis of trace
      heavy metals is urgently required by dynamic environmental monitoring and
      management, and TXRF has potential in this application domain. However, it calls
      for an online analysis scheme based on TXRF as well as a robust and rapid
      quantification method, which have not been well explored yet. Besides, spectral
      overlapping and background effects may lead to loss of accuracy or even faulty
      results during practical quantitative TXRF analysis. This paper proposes an
      intelligent, multi-element quantification method according to the established
      online TXRF analysis platform. In the intelligent quantification method,
      collected characteristic curves of all existing elements and a pre-estimated
      background curve in the whole spectrum scope are used to approximate the measured
      spectrum. A novel hybrid algorithm, PSO-RBFN-SA, is designed to solve the curve
      fitting problem, with offline global optimization and fast online computing.
      Experimental results verify that simultaneous quantification of trace heavy
      metals, including Cr, Mn, Fe, Co, Ni, Cu and Zn, is realized on the online TXRF
      analysis platform, and both high measurement precision and computational
      efficiency are obtained. 

PMID- 25954951
TI  - A Label-Free Impedimetric DNA Sensor Based on a Nanoporous SnO2 Film: Fabrication
      and Detection Performance.
AB  - Nanoporous SnO2 thin films were elaborated to serve as sensing electrodes for
      label-free DNA detection using electrochemical impedance spectroscopy (EIS).
      Films were deposited by an electrodeposition process (EDP). Then the non-Faradic
      EIS behaviour was thoroughly investigated during some different steps of
      functionalization up to DNA hybridization. The results have shown a systematic
      decrease of the impedance upon DNA hybridization. The impedance decrease is
      attributed to an enhanced penetration of ionic species within the film volume.
      Besides, the comparison of impedance variations upon DNA hybridization between
      the liquid and vapour phase processes for organosilane (APTES) grafting on the
      nanoporous SnO2 films showed that vapour-phase method is more efficient. This is
      due to the fact that the vapour is more effective than the solution in
      penetrating the nanopores of the films. As a result, the DNA sensors built from
      vapour-treated silane layer exhibit a higher sensitivity than those produced from
      liquid-treated silane, in the range of tested target DNA concentration going to
      10 nM. Finally, the impedance and fluorescence response signals strongly depend
      on the types of target DNA molecules, demonstrating a high selectivity of the
      process on nanoporous SnO2 films. 

PMID- 25954950
TI  - Classifying step and spin turns using wireless gyroscopes and implications for
      fall risk assessments.
AB  - Recent studies have reported a greater prevalence of spin turns, which are more
      unstable than step turns, in older adults compared to young adults in laboratory
      settings. Currently, turning strategies can only be identified through visual
      observation, either in-person or through video. This paper presents two unique
      methods and their combination to remotely monitor turning behavior using three
      uniaxial gyroscopes. Five young adults performed 90 degrees  turns at slow,
      normal, and fast walking speeds around a variety of obstacles while instrumented
      with three IMUs (attached on the trunk, left and right shank). Raw data from 360
      trials were analyzed. Compared to visual classification, the two IMU methods'
      sensitivity/specificity to detecting spin turns were 76.1%/76.7% and 76.1%/84.4%,
      respectively. When the two methods were combined, the IMU had an overall 86.8%
      sensitivity and 92.2% specificity, with 89.4%/100% sensitivity/specificity at
      slow speeds. This combined method can be implemented into wireless fall
      prevention systems and used to identify increased use of spin turns. This method
      allows for longitudinal monitoring of turning strategies and allows researchers
      to test for potential associations between the frequency of spin turns and
      clinically relevant outcomes (e.g., falls) in non-laboratory settings. 

PMID- 25954952
TI  - Development of an ultrasonic airflow measurement device for ducted air.
AB  - In this study, an in-duct ultrasonic airflow measurement device has been
      designed, developed and tested. The airflow measurement results for a small range
      of airflow velocities and temperatures show that the accuracy was better than
      3.5% root mean square (RMS) when it was tested within a round or square duct
      compared to the in-line Venturi tube airflow meter used for reference. This proof
      of concept device has provided evidence that with further development it could be
      a low-cost alternative to pressure differential devices such as the orifice plate
      airflow meter for monitoring energy efficiency performance and reliability of
      ventilation systems. The design uses a number of techniques and design choices to
      provide solutions to lower the implementation cost of the device compared to
      traditional airflow meters. The design choices that were found to work well are
      the single sided transducer arrangement for a "V" shaped reflective path and the
      use of square wave transmitter pulses ending with the necessary 180 degrees 
      phase changed pulse train to suppress transducer ringing. The device is also
      designed so that it does not have to rely on high-speed analogue to digital
      converters (ADC) and intensive digital signal processing, so could be implemented
      using voltage comparators and low-cost microcontrollers. 

PMID- 25954953
TI  - Enantioselective Recognition of Chiral Carboxylic Acids by a beta-Amino Acid and
      1,10-Phenanthroline Based Chiral Fluorescent Sensor.
AB  - A novel chiral 1,10-phenanthroline-based fluorescent sensor was designed and
      synthesized from optical active beta-amino acids. It used 1,10-phenanthroline
      moiety as a fluorescent signaling site and binding site, with optically active
      beta-amino acids as a chiral barrier site. Notably, the optically active beta
      amino acids were obtained by a Lewis base catalyzed hydrosilylation of beta
      enamino esters according to our former work. The chiral sensor has been used to
      conduct the enantioselective recognition of chiral mono and dicarboxylic acids
      derivatives. Using this fluorescent sensor, a moderate "turn-off" fluorescence
      diminishment response towards enantiomer of tartaric acids, and proline was
      observed. It found that l-enantiomers quench the chiral fluorescence sensor more
      efficiently than d-enantiomers due to the absolute configuration of the beta
      amino acid. 

PMID- 25954955
TI  - Carbon fiber epoxy composites for both strengthening and health monitoring of
      structures.
AB  - This paper presents a study of the electrical and mechanical behavior of several
      continuous carbon fibers epoxy composites for both strengthening and monitoring
      of structures. In these composites, the arrangement of fibers was deliberately
      diversified to test and understand the ability of the composites for self-sensing
      low strains. Composites with different arrangements of fibers and textile weaves,
      mainly unidirectional continuous carbon reinforced composites, were tested at the
      dynamometer. A two-probe method was considered to measure the relative electrical
      resistance of these composites during loading. The measured relative electrical
      resistance includes volume and contact electrical resistances. For all tested
      specimens, it increases with an increase in tensile strain, at low strain values.
      This is explained by the improved alignment of fibers and resulting reduction of
      the number of possible contacts between fibers during loading, increasing as a
      consequence the contact electrical resistance of the composite. Laboratory tests
      on strengthening of structural elements were also performed, making hand-made
      composites by the "wet process", which is commonly used in civil engineering for
      the strengthening of all types of structures in-situ. Results show that the woven
      epoxy composite, used for strengthening of concrete elements is also able to
      sense low deformations, below 1%. Moreover, results clearly show that this
      textile sensor also improves the mechanical work of the strengthened structural
      elements, increasing their bearing capacity. Finally, the set of obtained results
      supports the concept of a textile fabric capable of both structural upgrade and
      self-monitoring of structures, especially large structures of difficult access
      and needing constant, sometimes very expensive, health monitoring. 

PMID- 25954954
TI  - Accuracy of a custom physical activity and knee angle measurement sensor system
      for patients with neuromuscular disorders and gait abnormalities.
AB  - Long-term assessment of ambulatory behavior and joint motion are valuable tools
      for the evaluation of therapy effectiveness in patients with neuromuscular
      disorders and gait abnormalities. Even though there are several tools available
      to quantify ambulatory behavior in a home environment, reliable measurement of
      joint motion is still limited to laboratory tests. The aim of this study was to
      develop and evaluate a novel inertial sensor system for ambulatory behavior and
      joint motion measurement in the everyday environment. An algorithm for behavior
      classification, step detection, and knee angle calculation was developed. The
      validation protocol consisted of simulated daily activities in a laboratory
      environment. The tests were performed with ten healthy subjects and eleven
      patients with multiple sclerosis. Activity classification showed comparable
      performance to commercially available activPAL sensors. Step detection with our
      sensor system was more accurate. The calculated flexion-extension angle of the
      knee joint showed a root mean square error of less than 5 degrees  compared with
      results obtained using an electro-mechanical goniometer. This new system combines
      ambulatory behavior assessment and knee angle measurement for long-term
      measurement periods in a home environment. The wearable sensor system
      demonstrated high validity for behavior classification and knee joint angle
      measurement in a laboratory setting. 

PMID- 25954956
TI  - Multiple Leader Candidate and Competitive Position Allocation for Robust
      Formation against Member Robot Faults.
AB  - This paper proposes a Multiple Leader Candidate (MLC) structure and a Competitive
      Position Allocation (CPA) algorithm which can be applicable for various
      applications including environmental sensing. Unlike previous formation
      structures such as virtual-leader and actual-leader structures with position
      allocation including a rigid allocation and an optimization based allocation, the
      formation employing the proposed MLC structure and CPA algorithm is robust
      against the fault (or disappearance) of the member robots and reduces the entire
      cost. In the MLC structure, a leader of the entire system is chosen among leader
      candidate robots. The CPA algorithm is the decentralized position allocation
      algorithm that assigns the robots to the vertex of the formation via the
      competition of the adjacent robots. The numerical simulations and experimental
      results are included to show the feasibility and the performance of the multiple
      robot system employing the proposed MLC structure and the CPA algorithm. 

PMID- 25954958
TI  - Evaluation of the Antigenotoxic Effects of the Royal Sun Mushroom, Agaricus
      brasiliensis (Higher Basidiomycetes) in Human Lymphocytes Treated with Thymol in
      the Comet Assay.
AB  - The aim of this investigation was to evaluate the possible protective activity of
      Agaricus brasiliensis (=A. blazei sensu Murrill) ethanol extract against thymol
      induced DNA damage in human lymphocytes. Before we studied the possible
      interaction of thymol and A. brasiliensis extract, each component was tested in
      the comet assay. Thymol significantly increased DNA damage in human lymphocytes
      at higher concentrations (20, 50, 100, 150, and 200 ug/mL), whereas no genotoxic
      effect of A. brasiliensis ethanol extract was observed. In simultaneous treatment
      with thymol (200 ug/mL) and A. brasiliensis ethanol extract (50, 100, 150, and
      200 ug/mL), the latter failed to reduce a thymol-induced DNA damaging effect
      regardless of the applied concentrations. To confirm that thymol induces DNA
      damage via reactive oxygen species, we performed cotreatment with quercetin.
      Cotreatment with quercetin (100 and 500 umol/L) significantly reduced DNA damage
      caused by thymol (200 ug/mL), indicating that thymol exhibits genotoxicity mainly
      through induction of reactive oxygen species. 

PMID- 25954957
TI  - Increased expression of neuropilin 1 in melanoma progression and its prognostic
      significance in patients with melanoma.
AB  - Neuropilin 1 (NRP1), a receptor of vascular endothelial growth factor (VEGF),
      promotes angiogenesis, tumor growth, tumor invasion and metastasis. However, the
      function of NRP1 in melanoma progression, as well as the effect of NRP1
      expression on the prognosis of patients with melanoma remains unknown. In the
      present study, NRP1 expression was examined in 460 cases of melanocytic lesions
      (28 common nevi, 51 dysplastic nevi, 250 primary melanoma and 131 metastatic
      melanoma) at different stages, using a tissue microarray. The correlation of NRP1
      expression with melanoma progression, and its prognostic value in patients with
      melanoma was examined. In addition, the correlation between matrix
      metalloproteinase 2 (MMP2) and NRP1 expression in patients with melanoma was
      analyzed. The results demonstrated that NRP1 expression was significantly
      increased in primary (56%) and metastatic melanoma (62%), compared with common
      nevi (11%) and dysplastic nevi (24%). Notably, increased NRP1 expression was
      correlated with a poorer overall, and disease-specific, 10-year survival (P=0.03
      and P=0.002, respectively). Multivariate Cox regression analyses indicated that
      NRP1 is an independent prognostic marker for melanoma. Furthermore, a significant
      positive correlation between NRP1 and MMP2 expression in melanoma biopsies was
      observed, and their concomitant expression was closely correlated with melanoma
      patient survival, further supporting the hypothesis that the expression of NRP1
      is associated with melanoma invasion and metastasis. In conclusion, increased
      NRP1 expression is associated with disease progression and reduced survival in
      patients with melanoma, and is a promising prognostic molecular marker for this
      disease.

PMID- 25954959
TI  - Effects of Comb Tooth Cap Medicinal Mushroom, Hericium ramosum (Higher
      Basidiomycetes) Mycelia on DPPH Radical Scavenging Activity and Nerve Growth
      Factor Synthesis.
AB  - The goal of this study was to evaluate the antioxidant effects of and nerve
      growth factor (NGF) synthesis caused by Hericium ramosum mycelia. Wild mushroom
      fruiting bodies were collected from nature to isolate their mycelia. Pieces of H.
      ramosum fruiting bodies were plated onto 90-mm Petri dishes with potato dextrose
      agar medium to isolate their mycelia. Antioxidant activity was measured using 1,1
      diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging activity in vitro; the
      ethanol extract from H. ramosum mycelia (63.11 umol Trolox/g) was more potent
      than that of other mushroom mycelia extracts. There was a proportional
      relationship (R2 = 0.7929) between DPPH radical scavenging activity and total
      phenolic content in extracts of different mushroom mycelia. We investigated the
      ability of H. ramosum mycelia to inducing NGF synthesis in vivo. Oral
      administration of H. ramosum mycelia significantly increased concentrations of
      NGF in the hippocampus of intact mice. These results are the first concerning
      antioxidant activity and NGF synthesis of H. ramosum mycelia. These mushroom
      mycelia could be useful as food and/or nutritional supplements because of certain
      biological functions. 

PMID- 25954960
TI  - The Effect of Agaricus brasiliensis and Ganoderma lucidum Medicinal Mushroom
      Administration on the L-arginine/Nitric Oxide System and Rat Leukocyte Apoptosis
      in Experimental Type 1 Diabetes Mellitus.
AB  - Oxidative-nitrative stress develops as a result of hyperglycemia under diabetes
      mellitus. Formation of excessive reactive oxygen species and reactive nitrogen
      species leads to different cytotoxic effects and ultimately to increased cell
      death by apoptosis of immune-competent blood cells. This study showed the
      influence of medicinal mushroom (MM) administration on the L-arginine/nitric
      oxide (NO) system and rat leukocyte apoptosis under normal and experimental
      diabetic conditions. Animals were divided into 6 groups: (1) control, (2) control
      animals treated with Agaricus brasiliensis, (3) control animals treated with
      Ganoderma lucidum, (4) animals with experimental diabetes (EDM), (5) diabetic
      animals treated with A. brasiliensis, and (6) diabetic animals treated with G.
      lucidum. Control and diabetic animals were fed powdered mushrooms at a dose of 1
      g/kg body weight. Administration of MMs to animals with diabetes caused a
      decrease in the activity of the NO synthase enzyme, as well as in the content of
      stable end products of NO metabolism-nitrates and nitrites-at the control level.
      The normalizing effect of mushrooms on the percentage of leukocytes that contain
      pro- (p53) and antiapoptotic (Bcl-2) proteins compared with the EDM group was
      shown by immunocytochemical analysis. Thus the administration of MMs under EDM
      showed a positive corrective action on the L-arginine/NO system and the ratio
      between p53 and Bcl-2 proteins in white blood cells, as well as on apoptotic
      index reduction. 

PMID- 25954961
TI  - Evaluation of carbohydrate metabolism inhibition by some species of medicinal
      mushrooms from India.
AB  - Diabetes mellitus is one of the most common endocrine diseases. One antidiabetic
      therapeutic approach is to reduce gastrointestinal glucose production and
      absorption through the inhibition of alpha-amylase and alpha-amyloglucosidase
      enzymes, thereby preventing an increase in the postprandial glucose concentration
      in diabetics. The main aim of this study was to evaluate the antidiabetic
      potential of hydroalcoholic extracts of 3 mushrooms, that is, Ganoderma
      philippii, Lenzites elegans, and Rigidoporus ulmarius, using an in vitro
      enzymatic starch digestion assay model. The alpha-amylase and alpha-glucosidase
      inhibitory potential of hydroalcoholic mushroom extracts was tested at
      concentrations of 1, 5, 10, 12.5, 25, 50, and 100 mg/mL. Acarbose was used as a
      control. The amount of glucose liberated (micrograms) was determined using the
      3,5-dinitrosalicylic acid method. Phytochemical screening revealed the presence
      of carbohydrates in all examined species. In the case of G. philippii and L.
      elegans, a concentration-dependent increase in the percentage inhibition of
      enzyme activity was observed, with maximum inhibition at a concentration of 100
      mg/mL (40.22% +/- 0.83% and 26.57% +/- 0.68%, respectively). R. ulmarius showed
      maximum inhibitory activity at a concentration of 100 mg/mL (65.54% +/- 0.91%),
      and this was comparable to acarbose. 

PMID- 25954962
TI  - Biological Activities of Ethanol Extracts of Phellinus baumii (Higher
      Basidiomycetes) Obtained by Different Fermentation Methods.
AB  - Phellinus baumii was used for fermentation, and 3 corresponding ethanol extracts
      were obtained by 3 different methods: extract I, liquid fermentation; extract II,
      solid fermentation in polypropylene plastic bags with medium mainly consisting of
      sawdust and wheat bran; and extract III, solid fermentation in culture bottles
      with medium mainly consisting of rice. Ethanol extract I presented the best
      inhibition ability on HepG2 cell growth; inhibiting rates were 48.2% and 65.0% at
      doses of 10 and 100 ug/mL, respectively. Ethanol extracts II and III had a better
      regeneration effect on injured PC12 neural cells than extract I. The superoxide
      radical, hydrogen peroxide radical, and DPPH radical scavenging activities of
      ethanol extract III was better than those of the other 2 extracts. 

PMID- 25954963
TI  - Genetic resources and mycelial characteristics of several medicinal polypore
      mushrooms (Polyporales, Basidiomycetes).
AB  - Mycelial characteristics of dikaryotic collections of 6 medicinal polypore
      mushrooms (Fomes fomentarius, Fomitopsis pinicola, Ganoderma adspersum, G.
      applanatum, G. lucidum, and G. resinaceum) with different geographical origins
      (Armenia, China, France, Iran, Italy, and Russia) were screened. A total of 42
      polypore collections were molecularly identified by sequencing the internal
      transcribed spacer region of the ribosomal RNA genes' cluster, and a phylogenetic
      tree was constructed. Morphological characteristics of 37 cultures were observed
      on agar media (malt extract agar, potato dextrose agar) at different temperatures
      (25, 30, 35, and 38 degrees C) at a pH of 6.0. Colony morphology, pigmentation of
      mycelium and agar, mycelial growth rate, in vitro teleomorph formation, and other
      macromorphological characteristics were thoroughly described and illustrated.
      Micromorphological features of mycelia, such as different hyphal structures,
      clamp cells, presence and type of asexual sporulation, chlamydospores, and others
      were observed. The taxonomic significance of the mycelial characteristics
      revealed was estimated. The obtained results will assist further biotechnological
      cultivation of medicinal polypore mushrooms to develop novel health care
      biotechnological products. 

PMID- 25954964
TI  - Effect of L-Cysteine Pretreatment on the Control of Formaldehyde and Browning of
      the Culinary-Medicinal Shiitake Mushroom, Lentinus edodes (Higher Basidiomycetes)
      during Drying and Canning Processes.
AB  - Fresh culinary-medicinal Shiitake mushrooms (Lentinus edodes) were pretreated by
      soaking in 0.1 mg/mL of L-cysteine solution for 1 hour; then the variation in
      formaldehyde content and browning degree were studied during hot air-drying and
      canning processes. The results indicated that L-cysteine pretreatment
      significantly inhibited the increase of formaldehyde content and browning during
      the drying process; these increases in the pretreatment groups ranged from 7.0%
      to 14.0% and 65.4% to 68.9%, respectively, of that of the control groups. While
      the L-cysteine pretreatment did not seem to have a significant effect on
      controlling the formaldehyde content during the canning process, the increase of
      the browning degree of the canned products of the pretreatment groups ranged from
      64.8% to 78.5% of that of the control groups, indicating the inhibitive effect of
      L-cysteine on browning during the canning process of L. edodes. Overall, L
      cysteine pretreatment improved the sensory quality of both dried and canned L.
      edodes. 

PMID- 25954965
TI  - The Effects of Light Intensity, Casing Layers, and Layering Styles on Royal Sun
      Medicinal Mushroom, Agaricus brasiliensis (Higher Basidiomycetes) Cultivation in
      Turkey.
AB  - The aim of this research is to evaluate the effects of light intensity, casing
      layers, and layering styles on the production of the culinary-medicinal mushroom
      Agaricus brasiliensis in Turkey. The experiments were designed in split-split
      plots and replicated twice. Three different light intensities-I1, 350 lux; I2,
      450 lux; and I3, 750 lux-were used in main plots as environmental factors. A
      mixture of 4 different casing layers- peat (100%), peat-perlite (75%:25%), peat
      clinoptilolite (75%:25%), and peat-perlite-clinoptilolite (60%:20%:20%)-were used
      at split plots and at split plots. S1, a flat, 3-cm casing layer; S2, a flat, 5
      cm casing layer; and S3, casing soil ridges 10 cm wide * 4 cm high, 10 cm apart,
      were deposited on top of 1-cm overall soil casing layers. At the end of the
      harvest phase, the total yield was estimated per 100 kg of substrate. Biological
      efficiency (percentage) was determined from the fresh weight of the mushrooms and
      the dry weight of the compost at the end of the harvesting period. The highest
      total yield (7.2 kg/100 kg compost) and biological efficiency (27.63%) were
      achieved from I2 * peat-perlite-clinoptilolite * S2 treatment. Influence of light
      intensity, casing layer, layering style, and their interaction in treatments with
      color values (L*, a*, b*, chroma*, and hue*) also were examined. It has been
      shown that within color values, chroma* (saturation) values of mushroom caps were
      affected by light intensity, casing layer, and layering style treatments and
      light intensity * casing layer treatments and the brightness of mushroom caps
      tended to increase as light intensity increased. 

PMID- 25954966
TI  - In Vitro Assessment of Extracts of the Lingzhi or Reishi Medicinal Mushroom,
      Ganoderma lucidum (Higher Basidiomycetes) Against Different Plant Pathogenic
      Fungi.
AB  - Five isolates of the lingzhi or reishi medicinal mushroom Ganoderma lucidum (GL
      1, GL-2, GL-3, GL-4, GL-5) were collected from different locations within and
      surrounding Lahore, Pakistan, to study the antifungal potential of their
      bioactive compounds. After studying morphology, different concentrations of the
      extracts were prepared in methanol and water using a Soxhlet extractor. Different
      cultures of fungal pathogens were acquired from the First Fungal Culture Bank of
      Pakistan, University of the Punjab, Lahore. The antimicrobial potential of 5 G.
      lucidum samples against 5 fungal pathogens (Fusarium oxysporum, Aspergillus
      niger, A. flavus, Penicillium sp., and Alternaria alternata) was observed. The
      lowest biomass reduction (7%) was observed in 1% and 2% concentrations of a
      methanolic extract and 6% in the case of a water extract. Major inhibition was
      observed using higher concentrations of the methanolic extract (3% and 4%). These
      extracts significantly suppressed fungal biomass up to 38% and 56% in A. niger,
      47% in A. flavus, 58% in ,i>Penicillium sp., 46% in A. alternaria, and 45% in F.
      oxysporum compared with the control. It was concluded from these studies that
      methanolic extracts of G. lucidum showed better activity against all plant fungal
      pathogens when compared with the water extracts. 

PMID- 25954967
TI  - Effects of short term bioturbation by common voles on biogeochemical soil
      variables.
AB  - Bioturbation contributes to soil formation and ecosystem functioning. With
      respect to the active transport of matter by voles, bioturbation may be
      considered as a very dynamic process among those shaping soil formation and
      biogeochemistry. The present study aimed at characterizing and quantifying the
      effects of bioturbation by voles on soil water relations and carbon and nitrogen
      stocks. Bioturbation effects were examined based on a field set up in a luvic
      arenosol comprising of eight 50 * 50 m enclosures with greatly different numbers
      of common vole (Microtus arvalis L., ca. 35-150 individuals ha-1 mth-1). Eleven
      key soil variables were analyzed: bulk density, infiltration rate, saturated
      hydraulic conductivity, water holding capacity, contents of soil organic carbon
      (SOC) and total nitrogen (N), CO2 emission potential, C/N ratio, the stable
      isotopic signatures of 13C and 15N, and pH. The highest vole densities were
      hypothesized to cause significant changes in some variables within 21 months.
      Results showed that land history had still a major influence, as eight key
      variables displayed an additional or sole influence of topography. However, the
      delta15N at depths of 10-20 and 20-30 cm decreased and increased with increasing
      vole numbers, respectively. Also the CO2 emission potential from soil collected
      at a depth of 15-30 cm decreased and the C/N ratio at 5-10 cm depth narrowed with
      increasing vole numbers. These variables indicated the first influence of voles
      on the respective mineralization processes in some soil layers. Tendencies of
      vole activity homogenizing SOC and N contents across layers were not significant.
      The results of the other seven key variables did not confirm significant effects
      of voles. Thus overall, we found mainly a first response of variables that are
      indicative for changes in biogeochemical dynamics but not yet of those
      representing changes in pools. 

PMID- 25954968
TI  - Benefits of Turbid River Plume Habitat for Lake Erie Yellow Perch (Perca
      flavescens) Recruitment Determined by Juvenile to Larval Genotype Assignment.
AB  - Nutrient-rich, turbid river plumes that are common to large lakes and coastal
      marine ecosystems have been hypothesized to benefit survival of fish during early
      life stages by increasing food availability and (or) reducing vulnerability to
      visual predators. However, evidence that river plumes truly benefit the
      recruitment process remains meager for both freshwater and marine fishes. Here,
      we use genotype assignment between juvenile and larval yellow perch (Perca
      flavescens) from western Lake Erie to estimate and compare recruitment to the age
      0 juvenile stage for larvae residing inside the highly turbid, south-shore Maumee
      River plume versus those occupying the less turbid, more northerly Detroit River
      plume. Bayesian genotype assignment of a mixed assemblage of juvenile (age-0)
      yellow perch to putative larval source populations established that recruitment
      of larvae was higher from the turbid Maumee River plume than for the less turbid
      Detroit River plume during 2006 and 2007, but not in 2008. Our findings add to
      the growing evidence that turbid river plumes can indeed enhance survival of fish
      larvae to recruited life stages, and also demonstrate how novel population
      genetic analyses of early life stages can contribute to determining critical
      early life stage processes in the fish recruitment process. 

PMID- 25954969
TI  - Resveratrol ameliorates renal damage, increases expression of heme oxygenase-1,
      and has anti-complement, anti-oxidative, and anti-apoptotic effects in a murine
      model of membranous nephropathy.
AB  - BACKGROUND: Idiopathic membranous nephropathy (MN) is an autoimmune-mediated
      glomerulonephritis and a common cause of nephrotic syndrome in adults. There are
      limited available treatments for MN. We assessed the efficacy of resveratrol
      (RSV) therapy for treatment of MN in a murine model of this disease. METHODS:
      Murine MN was experimentally induced by daily subcutaneous administration of
      cationic bovine serum albumin, with phosphate-buffered saline used in control
      mice. MN mice were untreated or given RSV. Disease severity and pathogenesis was
      assessed by determination of metabolic and histopathology profiles, lymphocyte
      subsets, immunoglobulin production, oxidative stress, apoptosis, and production
      of heme oxygenase-1 (HO1). RESULTS: MN mice given RSV had significantly reduced
      proteinuria and a marked amelioration of glomerular lesions. RSV also
      significantly attenuated immunofluorescent staining of C3, although there were no
      changes of serum immunoglobulin levels or immunocomplex deposition in the
      kidneys. RSV treatment of MN mice also reduced the production of reactive oxygen
      species (ROS), reduced cell apoptosis, and upregulated heme oxygenase 1 (HO1).
      Inhibition of HO1 with tin protoporphyrin IX partially reversed the
      renoprotective effects of RSV. The HO1 induced by RSV maybe via Nrf2 signaling.
      CONCLUSION: Our results show that RSV increased the expression of HO1 and
      ameliorated the effects of membranous nephropathy in a mouse model due to its
      anti-complement, anti-oxidative, and anti-apoptotic effects. RSV appears to have
      potential as a treatment for MN.

PMID- 25954970
TI  - Differential requirements of singleplex and multiplex recombineering of large DNA
      constructs.
AB  - Recombineering is an in vivo genetic engineering technique involving homologous
      recombination mediated by phage recombination proteins. The use of recombineering
      methodology is not limited by size and sequence constraints and therefore has
      enabled the streamlined construction of bacterial strains and multi-component
      plasmids. Recombineering applications commonly utilize singleplex strategies and
      the parameters are extensively tested. However, singleplex recombineering is not
      suitable for the modification of several loci in genome recoding and strain
      engineering exercises, which requires a multiplex recombineering design. Defining
      the main parameters affecting multiplex efficiency especially the insertion of
      multiple large genes is necessary to enable efficient large-scale modification of
      the genome. Here, we have tested different recombineering operational parameters
      of the lambda phage Red recombination system and compared singleplex and
      multiplex recombineering of large gene sized DNA cassettes. We have found that
      optimal multiplex recombination required long homology lengths in excess of 120
      bp. However, efficient multiplexing was possible with only 60 bp of homology.
      Multiplex recombination was more limited by lower amounts of DNA than singleplex
      recombineering and was greatly enhanced by use of phosphorothioate protection of
      DNA. Exploring the mechanism of multiplexing revealed that efficient
      recombination required co-selection of an antibiotic marker and the presence of
      all three Red proteins. Building on these results, we substantially increased
      multiplex efficiency using an ExoVII deletion strain. Our findings elucidate key
      differences between singleplex and multiplex recombineering and provide important
      clues for further improving multiplex recombination efficiency. 

PMID- 25954971
TI  - HMGB1 translocation is involved in the transformation of autophagy complexes and
      promotes chemoresistance in leukaemia.
AB  - Acute lymphoblastic leukaemia (ALL) is a common paediatric cancer and is among
      the most curable cancers. However, the acquisition of drug resistance is a
      significant obstacle to the achievement of favourable outcomes, and autophagy is
      regarded as a mechanism that underlies chemoresistance. In this study, RT-qPCR
      was used to measure the expression of HMGB1 and Beclin1 in bone marrow
      mononuclear cells. A CCK-8 test was conducted to assess cell viability. Western
      blot, immunofluorescence and transmission electron microscopic analyses were
      performed to evaluate the autophagy levels. Immunoprecipitation analysis was
      performed to detect protein-protein interactions in the autophagy complexes. We
      found that HMGB1 expression correlated with the clinical status of ALL. In vitro,
      anticancer agent-induced cytotoxic effects were associated with autophagy-related
      drug resistance, and these effects were ameliorated by FIP200 depletion or the
      application of autophagy inhibitors. Moreover, the Ulk1-Atg13-FIP200 complex,
      which promotes HMGB1 trafficking, acted upstream of the HMGB1-Beclin1 and PI3KC3
      Beclin1 complexes and played a critical role in autophagy. Targeting the
      transformation of autophagic complexes or HMGB1 translocation may suppress
      autophagy and consequently overcome chemoresistance in leukaemia.

PMID- 25954972
TI  - Loss of Expression of Reprimo, a p53-induced Cell Cycle Arrest Gene, Correlates
      with Invasive Stage of Tumor Progression and p73 Expression in Gastric Cancer.
AB  - Reprimo (RPRM), a downstream effector of p53-induced cell cycle arrest at G2/M,
      has been proposed as a putative tumor suppressor gene (TSG) and as a potential
      biomarker for non-invasive detection of gastric cancer (GC). The aim of this
      study was to evaluate the epigenetic silencing of RPRM gene by promoter
      methylation and its tumor suppressor function in GC cell lines. Furthermore,
      clinical significance of RPRM protein product and its association with p53/p73
      tumor suppressor protein family was explored. Epigenetic silencing of RPRM gene
      by promoter methylation was evaluated in four GC cell lines. Protein expression
      of RPRM was evaluated in 20 tumor and non-tumor matched cases. The clinical
      significance of RPRM association with p53/p73 tumor suppressor protein family was
      assessed in 114 GC cases. Tumor suppressor function was examined through
      functional assays. RPRM gene expression was negatively correlated with promoter
      methylation (Spearman rank r = -1; p = 0.042). RPRM overexpression inhibited
      colony formation and anchorage-independent growth. In clinical samples, RPRM gene
      protein expression was detected in 75% (15/20) of non-tumor adjacent mucosa, but
      only in 25% (5/20) of gastric tumor tissues (p = 0.001). Clinicopathological
      correlations of loss of RPRM expression were significantly associated with
      invasive stage of GC (stage I to II-IV, p = 0.02) and a positive association
      between RPRM and p73 gene protein product expression was found (p<0.0001 and
      kappa value = 0.363). In conclusion, epigenetic silencing of RPRM gene by
      promoter methylation is associated with loss of RPRM expression. Functional
      assays suggest that RPRM behaves as a TSG. Loss of expression of RPRM gene
      protein product is associated with the invasive stage of GC. Positive association
      between RPRM and p73 expression suggest that other members of the p53 gene family
      may participate in the regulation of RPRM expression. 

PMID- 25954973
TI  - Effect of mechanical deformation on the structure of regenerated Bombyx mori silk
      fibroin films as revealed using Raman and infrared spectroscopy.
AB  - To better understand the effect of mechanical stress during the spinning of silk,
      the protein orientation and conformation of Bombyx mori regenerated silk fibroin
      (RSF) films have been studied as a function of deformation in a static mode or in
      real time by tensile-Raman experiments and polarization modulation infrared
      linear dichroism (PM-IRLD), respectively. The data show that either for step-by
      step or continuous stretching, elongation induces the progressive formation of
      beta-sheets that align along the drawing axis, in particular above a draw ratio
      of ~2. The formation of beta-sheets begins before their alignment during a
      continuous drawing. Unordered chains were, however, never found to be oriented,
      which explains the very low level of orientation of the amorphous phase of the
      natural fiber. Stress-perturbed unordered chains readily convert into beta
      sheets, the strain-induced transformation following a two-state process. The
      final level of orientation and beta-sheet content are lower than those found in
      the native fiber, indicating that various parameters have to be optimized in
      order to implement a spinning process as efficient as the natural one. Finally,
      during the stress relaxation period in a step-by-step drawing, there is
      essentially no change of the content and orientation of the beta-sheets,
      suggesting that only unordered structures tend to reorganize. 

PMID- 25954974
TI  - Berberine Inhibits Invasion and Metastasis of Colorectal Cancer Cells via COX
      2/PGE2 Mediated JAK2/STAT3 Signaling Pathway.
AB  - Berberin, extracted from Chinese herbal medicine Coptis chinensis, has been found
      to have anti-tumor activities. However, the underlying mechanisms have not been
      fully elucidated. Our current study demonstrated that berberin inhibited the in
      vitro and in vivo growth, migration/invasion of CRC cells, via attenuating the
      expression levels of COX-2/PGE2, following by reducing the phosphorylation of
      JAK2 and STAT3, as well as the MMP-2/-9 expression. We further clarified that an
      increase of COX-2/PGE2 expression offset the repressive activity of Berberin on
      JAK2/STAT3 signaling, and a JAK2 inhibitor AZD1480 blocked the effect of COX
      2/PGE2 on MMP-2/-9 expression. In summary, Berberin inhibited CRC invasion and
      metastasis via down-regulation of COX-2/PGE2- JAK2/STAT3 signaling pathway. 

PMID- 25954975
TI  - Autoantibody profiling on human proteome microarray for biomarker discovery in
      cerebrospinal fluid and sera of neuropsychiatric lupus.
AB  - Autoantibodies in cerebrospinal fluid (CSF) from patients with neuropsychiatric
      systemic lupus erythematosus (NPSLE) may be potential biomarkers for prediction,
      diagnosis, or prognosis of NPSLE. We used a human proteome microarray with~17,000
      unique full-length human proteins to investigate autoantibodies associated with
      NPSLE. Twenty-nine CSF specimens from 12 NPSLE, 7 non-NPSLE, and 10 control (non
      systemic lupus erythematosus)patients were screened for NPSLE-associated
      autoantibodies with proteome microarrays. A focused autoantigen microarray of
      candidate NPSLE autoantigens was applied to profile a larger cohort of CSF with
      patient-matched sera. We identified 137 autoantigens associated with NPSLE.
      Ingenuity Pathway Analysis revealed that these autoantigens were enriched for
      functions involved in neurological diseases (score = 43).Anti-proliferating cell
      nuclear antigen (PCNA) was found in the CSF of NPSLE and non-NPSLE patients. The
      positive rates of 4 autoantibodies in CSF specimens were significantly different
      between the SLE (i.e., NPSLE and non-NPSLE) and control groups: anti-ribosomal
      protein RPLP0, anti-RPLP1, anti-RPLP2, and anti-TROVE2 (also known as anti-Ro/SS
      A). The positive rate for anti-SS-A associated with NPSLE was higher than that
      for non-NPSLE (31.11% cf. 10.71%; P = 0.045).Further analysis showed that anti-SS
      A in CSF specimens was related to neuropsychiatric syndromes of the central
      nervous system in SLE (P = 0.009). Analysis with Spearman's rank correlation
      coefficient indicated that the titers of anti-RPLP2 and anti-SS-A in paired CSF
      and serum specimens significantly correlated. Human proteome microarrays offer a
      powerful platform to discover novel autoantibodies in CSF samples. Anti-SS-A
      autoantibodies may be potential CSF markers for NPSLE. 

PMID- 25954977
TI  - Development and comparison of two devices for treatment of onychomycosis by
      photodynamic therapy.
AB  - Onychomycosis is the most common nail disorder. The treatment for this type of
      infection is one of the main difficult ones in clinical practice, due to the fact
      that the nails are nonvascularized structures, which compromise the penetration
      of drugs delivered systemically and favor slow nail growth. We present two
      devices based on light-emitting diode arrays as light sources for the treatment
      of onychomycosis by photodynamic therapy (PDT). PDT is an emerging technique that
      uses a photosensitizer (PS) activated by light in the presence of oxygen. The PS
      absorbs energy from light and transfers it to oxygen, producing reactive oxygen
      species such as hydroxyl radicals, superoxide, and singlet oxygen which
      inactivate fungi and bacteria. Our proposal is the use of a portable and secure
      light source device in patients with onychomycosis. Additional advantages are the
      low cost involved, the possibility of topical treatment rather than systemic and
      the simplicity of operation. These advantages are important to ensure the
      implementation of this technology for the treatment of an impacting health
      problem.

PMID- 25954978
TI  - Improved quantitative analysis of spectra using a new method of obtaining
      derivative spectra based on a singular perturbation technique.
AB  - Spectroscopy is often applied when a rapid quantitative analysis is required, but
      one challenge is the translation of raw spectra into a final analysis. Derivative
      spectra are often used as a preliminary preprocessing step to resolve overlapping
      signals, enhance signal properties, and suppress unwanted spectral features that
      arise due to non-ideal instrument and sample properties. In this study, to
      improve quantitative analysis of near-infrared spectra, derivatives of noisy raw
      spectral data need to be estimated with high accuracy. A new spectral estimator
      based on singular perturbation technique, called the singular perturbation
      spectra estimator (SPSE), is presented, and the stability analysis of the
      estimator is given. Theoretical analysis and simulation experimental results
      confirm that the derivatives can be estimated with high accuracy using this
      estimator. Furthermore, the effectiveness of the estimator for processing noisy
      infrared spectra is evaluated using the analysis of beer spectra. The derivative
      spectra of the beer and the marzipan are used to build the calibration model
      using partial least squares (PLS) modeling. The results show that the PLS based
      on the new estimator can achieve better performance compared with the Savitzky
      Golay algorithm and can serve as an alternative choice for quantitative
      analytical applications. 

PMID- 25954976
TI  - The safety and efficacy of antifibrinolytic therapy in neonatal cardiac surgery.
AB  - BACKGROUND: Neonates undergoing open-heart surgery are particularly at risk of
      postoperative bleeding requiring blood transfusion. Aprotinin has attained high
      efficacy in reducing the requirement for a blood transfusion following a
      cardiopulmonary bypass, but is seldom studied in the neonatal age group. The aim
      of this study was to compare the efficacy and adverse effects of aprotinin and
      tranexamic acid in neonates undergoing open-heart surgery at a single centre.
      METHODS: Between October 2003 and March 2008, perioperative data of 552
      consecutive neonatal patients undergoing open-heart surgery in Children's
      Hospital Boston were reviewed. Among them, 177 did not receive antifibrinolytic
      therapy (Group A); 100 were treated with tranexamic acid only (Group B); and 275
      patients received aprotinin with or without tranexamic acid (Group C). Except for
      antifibrinolytic therapy, the anaesthesiological and surgical protocols remained
      identical. Postoperative complications and in-hospital mortality were the primary
      study endpoints. RESULTS: Body weight and Risk Adjustment for Congenital Heart
      Surgery (RACHS-1) scores were statistically comparable among the three groups. No
      statistically significant differences were observed between the duration of
      hospitalization, chest tube drainage, reexploration for bleeding, and kidney
      function impairment. In Group C, less blood was transfused within 24 hours than
      in GroupB. Operative mortality was similar among the three groups. CONCLUSION: No
      further risk and kidney injury were observed in the use of aprotinin in neonatal
      cardiac surgery, aprotinin demonstrated a reduced requirement for blood
      transfusion compared with tranexamic acid. Our data provide reasonable evidence
      that aprotinin and tranexamic acid are safe and efficacious as antifibrinolytic
      modalities in neonatal patients undergoing cardiac surgery.

PMID- 25954979
TI  - Ultrathin random copolymer-grafted layers for block copolymer self-assembly.
AB  - Hydroxyl-terminated P(S-r-MMA) random copolymers (RCPs) with molecular weights
      (Mn) from 1700 to 69000 and a styrene unit fraction of approximately 61% were
      grafted onto a silicon oxide surface and subsequently used to study the
      orientation of nanodomains with respect to the substrate, in cylinder-forming PS
      b-PMMA block copolymer (BCP) thin films. When the thickness (H) of the grafted
      layer is greater than 5-6 nm, a perpendicular orientation is always observed
      because of the efficient decoupling of the BCP film from the polar SiO2 surface.
      Conversely, if H is less than 5 nm, the critical thickness of the grafted layer,
      which allows the neutralization of the substrate and promotion of the
      perpendicular orientation of the nanodomains in the BCP film, is found to depend
      on the Mn of the RCP. In particular, when Mn = 1700, a 2.0 nm thick grafted layer
      is sufficient to promote the perpendicular orientation of the PMMA cylinders in
      the PS-b-PMMA BCP film. A proximity shielding mechanism of the BCP molecules from
      the polar substrate surface, driven by chain stretching of the grafted RCP
      molecules, is proposed. 

PMID- 25954980
TI  - Combination of magnetic and enhanced mechanical properties for copolymer-grafted
      magnetite composite thermoplastic elastomers.
AB  - Composite thermoplastic elastomers (CTPEs) of magnetic copolymer-grafted
      nanoparticles (magnetite, Fe3O4) were synthesized and characterized to generate
      magnetic CTPEs, which combined the magnetic property of Fe3O4 nanoparticles and
      the thermoplastic elasticity of the grafted amorphous polymer matrix. Fe3O4
      nanoparticles served as stiff, multiple physical cross-linking points
      homogeneously dispersed in the grafted poly(n-butyl acrylate-co-methyl
      methacrylate) rubbery matrix synthesized via the activators regenerated by
      electron transfer for atom transfer radical polymerization method (ARGET ATRP).
      The preparation technique for magnetic CTPEs opened a new route toward developing
      a wide spectrum of magnetic elastomeric materials with strongly enhanced
      macroscopic properties. Differential scanning calorimetry (DSC) was used to
      measure the glass transition temperatures, and thermogravimetric analysis (TGA)
      was used to examine thermal stabilities of these CTPEs. The magnetic property
      could be conveniently tuned by adjusting the content of Fe3O4 nanoparticles in
      CTPEs. Compared to their linear copolymers, these magnetic CTPEs showed
      significant increases in tensile strength and elastic recovery. In situ small
      angle X-ray scattering measurement was conducted to reveal the microstructural
      evolution of CTPEs during tensile deformation. 

PMID- 25954981
TI  - Copper(I)-Catalyzed Oxidation of Alkenes Using Molecular Oxygen and
      Hydroxylamines: Synthesis and Reactivity of alpha-Oxygenated Ketones.
AB  - The copper(I)-catalyzed oxidation of alkenes with molecular oxygen and N
      hydroxyphthalimide (NHPI) or N-hydroxybenzotriazole (HOBt) provided alpha
      oxygenated ketones. The reaction proceeded under a balloon of O2 at room
      temperature to furnish the dioxygenated products in 50-90% yield. These
      compounds, particularly the HOBt derivatives, can be further functionalized with
      phosphorus, nitrogen, and sulfur nucleophiles to give synthetically useful
      products. 

PMID- 25954982
TI  - AC Electric Field-Induced Trapping of Microparticles in Pinched
      Microconfinements.
AB  - The trapping of charged microparticles under confinement in a converging
      diverging microchannel, under a symmetric AC field of tunable frequency, is
      studied. We show that at low frequencies, the trapping characteristics stem from
      the competing effects of positive dielectrophoresis and the linear electrokinetic
      phenomena of electroosmosis and electrophoresis. It is found, somewhat
      unexpectedly, that electroosmosis and electrophoresis significantly affect the
      concentration profile of the trapped analyte, even for a symmetric AC field.
      However, at intermediate frequencies, the microparticle trapping mechanism is
      predominantly a consequence of positive dielectrophoresis. We substantiate our
      experimental results for the microparticle concentration distribution, along the
      converging-diverging microchannel, with a detailed theoretical analysis that
      takes into account all of the relevant frequency-dependent electrokinetic
      phenomena. This study should be useful in understanding the response of
      biological components such as cells to applied AC fields. Moreover, it will have
      potential applications in the design of efficient point-of-care diagnostic
      devices for detecting biomarkers and also possibly in some recent strategies in
      cancer therapy using AC fields. 

PMID- 25954983
TI  - Subunit Interactions within the Carbon-Phosphorus Lyase Complex from Escherichia
      coli.
AB  - Phosphonates are a large class of organophosphorus compounds with a
      characteristic carbon-phosphorus bond. The genes responsible for phosphonate
      utilization in Gram-negative bacteria are arranged in an operon of 14 genes. The
      carbon-phosphorus lyase complex, encoded by the genes phnGHIJKLM, catalyzes the
      cleavage of the stable carbon-phosphorus bond of organophosphonates to the
      corresponding hydrocarbon and inorganic phosphate. Recently, complexes of this
      enzyme containing five subunits (PhnG-H-I-J-K), four subunits (PhnG-H-I-J), and
      two subunits (PhnG-I) were purified after expression in Escherichia coli ( Proc.
      Natl. Acad. Sci., U. S. A. 2011 , 108 , 11393 ). Here we demonstrated using mass
      spectrometry, ultracentrifugation, and chemical cross-linking experiments that
      these complexes are formed from a PhnG2I2 core that is further elaborated by the
      addition of two copies each of PhnH and PhnJ to generate PhnG2H2I2J2. This
      complex adds an additional subunit of PhnK to form PhnG2H2I2J2K. Chemical cross
      linking of the five-component complex demonstrated that PhnJ physically interacts
      with both PhnG and PhnI. We were unable to demonstrate the interaction of PhnH or
      PhnK with any other subunits by chemical cross-linking. Hydrogen-deuterium
      exchange was utilized to probe for alterations in the dynamic properties of
      individual subunits within the various complexes. Significant regions of PhnG
      become less accessible to hydrogen/deuterium exchange from solvent within the
      PhnG2I2 complex compared with PhnG alone. Specific regions of PhnI exhibited
      significant differences in the H/D exchange rates in PhnG2I2 and PhnG2H2I2J2K. 

PMID- 25954984
TI  - Doubly bonded E13?P and B?E15 molecules and their reactions with H2,
      acetonitrile, benzophenone, and 2,3-dimethylbutadiene.
AB  - The bonding properties and the potential energy surfaces for the chemical
      reactions of doubly bonded compounds that have the >E13?E15< pattern are studied
      using density functional theory (M06-2X/Def2-SVPD). Nine molecules, >E13?P< (E13
      = B, Al, Ga, In, and Tl) and >B?E15< (E15 = N, P, As, Sb, and Bi), are used as
      model reactants in this work. Four types of chemical reactions, H2 addition,
      acetonitrile, benzophenone [2 + 2] cycloadditions, and dimethylbutadiene [4 + 2]
      cycloaddition, are used to study the chemical reactivity of these inorganic,
      ethylene-like molecules. The results of these theoretical analyses show that only
      the >B?P< molecule has a weak B?P double bond, while the >Al?P< , >Ga?P< , >In?P<
      , >Tl?P< , >B?N< , >B?As<, >B?Sb<, and >B?Bi< compounds are best described as
      having a strong single sigma bond, instead of a traditional p-p pi bond. The
      theoretical results also show that the singlet-triplet energy gap can be used to
      determine the relative reactivity of these doubly bonded molecules. According to
      these theoretical investigations, it is predicted that the order of reactivity is
      as follows: B?P > Al?P > Ga?P > In?P > Tl?P and B?N ? B?P < B?As < B?Sb < B?Bi.
      The conclusions drawn are consistent with the available experimental
      observations. 

PMID- 25954985
TI  - Stratification of risk for hospital admissions for injury related to fall: cohort
      study.
AB  - OBJECTIVE: To determine whether the ability to stratify an individual patient's
      hazard for falling could facilitate development of focused interventions aimed at
      reducing these adverse outcomes. DESIGN: Clinical and sociodemographic data from
      electronic health records were utilized to derive multiple logistic regression
      models of hospital readmissions for injuries related to falls. Drugs used at
      admission were summarized based on reported adverse effect frequencies in
      published drug labeling. SETTING: Two large academic medical centers in New
      England, United States. PARTICIPANTS: The model was developed with 25,924
      individuals age >= 40 with an initial hospital discharge. The resulting model was
      then tested in an independent set of 13,032 inpatients drawn from the same
      hospital and 36,588 individuals discharged from a second large hospital during
      the same period. MAIN OUTCOME MEASURE: Hospital readmissions for injury related
      to falls. RESULTS: Among 25,924 discharged individuals, 680 (2.6%) were evaluated
      in the emergency department or admitted to hospital for a fall within 30 days of
      discharge, 1635 (6.3%) within 180 days of discharge, 2360 (9.1%) within one year,
      and 3465 (13.4%) within two years. Older age, female sex, white or African
      American race, public insurance, greater number of drugs taken on discharge, and
      score for burden of adverse effects were each independently associated with
      hazard for fall. For drug burden, presence of a drug with a frequency of adverse
      effects related to fall of 10% was associated with 3.5% increase in odds of
      falling over the next two years (odds ratio 1.04, 95% confidence interval 1.02 to
      1.05). In an independent testing set, the area under the receiver operating
      characteristics curve was 0.65 for a fall within two years based on cross
      sectional data and 0.72 with the addition of prior utilization data including age
      adjusted Charlson comorbidity index. Portability was promising, with area under
      the curve of 0.71 for the longitudinal model in a second hospital system.
      CONCLUSIONS: It is potentially useful to stratify risk of falls based on clinical
      features available as artifacts of routine clinical care. A web based tool can be
      used to calculate and visualize risk associated with drug treatment to facilitate
      further investigation and application.

PMID- 25954986
TI  - Role of fear in overdiagnosis and overtreatment--an essay by Iona Heath.

PMID- 25954987
TI  - Mobile phone messaging to improve health.

PMID- 25954989
TI  - Routine thienopyridine pretreatment for acute coronary syndrome without ST
      elevation.

PMID- 25954990
TI  - Randomised controlled trials: "within subject" versus "between subject" designs.

PMID- 25954988
TI  - Reappraisal of thienopyridine pretreatment in patients with non-ST elevation
      acute coronary syndrome: a systematic review and meta-analysis.
AB  - OBJECTIVE: To investigate the effect of pretreatment with P2Y12 receptor
      inhibitors compared with no pretreatment on efficacy and safety of treatment of
      non-ST elevation acute coronary syndrome (ACS). DATA SOURCES: Two reviewers
      independently searched Medline, Embase, Cochrane Controlled Trials, and BioMed
      Central databases for randomized placebo controlled trials and observational
      studies from August 2001 to March 2014. STUDY ELIGIBILITY: Studies must have
      reported both all-cause mortality (primary efficacy endpoint) and major bleeding
      (safety endpoint) outcomes. DATA EXTRACTION: Data on sample size,
      characteristics, drug dose and delay of administration, and outcomes were
      independently extracted and analyzed. DATA SYNTHESIS: A random-effect model was
      applied. The analysis was performed (i) in all patients independently of the
      management strategy and (ii) only in patients undergoing percutaneous coronary
      intervention. RESULTS: Of the 393 titles identified, seven (four randomized
      controlled trials, one observational analysis from a randomized controlled trial,
      and three observational studies) met the inclusion criteria. No study was
      identified for ticagrelor or cangrelor, and analyses were thus limited to
      thienopyridines. A total of 32,383 non-ST elevation ACS patients were included,
      18,711 coming from randomized controlled trials. Of these, 55% underwent
      percutaneous coronary intervention (PCI). Pretreatment was not associated with a
      significant lower risk of mortality in all patients (odds ratio 0.90 (95%
      confidence interval 0.75 to 1.07), P=0.24), in particular when considering only
      the randomized controlled trials (odds ratio 0.90 (0.71 to 1.14), P=0.39).
      Similar results were observed in the cohort of patients undergoing PCI. A
      significant 30-45% excess of major bleeding was consistently observed in all
      patients (odds ratio 1.32 (1.16 to 1.49), P<0.0001) and in those undergoing PCI,
      as well as in the subset analyses of randomized controlled trials of these two
      cohorts of patients. There was a reduction in major adverse cardiovascular events
      in the analysis of all patients (odds ratio 0.84 (0.72 to 0.98), P=0.02), driven
      by the old clopidogrel studies (CURE and CREDO), but the difference was not
      significant for the cohort of patients undergoing PCI. Stent thrombosis, stroke,
      and urgent revascularization did not differ between groups (pretreatment v no
      pretreatment). The results were consistent for both thienopyridines and confirmed
      in sensitivity analyses. LIMITATIONS: Analysis was not performed on individual
      patient's data. CONCLUSION: In patients presenting with non-ST elevation ACS,
      pretreatment with thienopyridines is associated with no significant reduction of
      mortality but with a significant excess of major bleeding no matter the strategy
      adopted, invasive or not. Our results do not support a strategy of routine
      pretreatment in patients with non-ST elevation ACS.

PMID- 25954991
TI  - Hydrogen-rich saline reduces cell death through inhibition of DNA oxidative
      stress and overactivation of poly (ADP-ribose) polymerase-1 in retinal ischemia
      reperfusion injury.
AB  - Overactivation of poly (ADP-ribose) polymerase 1 (PARP-1), as a result of
      sustained DNA oxidation in ischemia-reperfusion injury, triggers programmed cell
      necrosis and apoptosis. The present study was conducted to demonstrate whether
      hydrogen-rich saline (HRS) has a neuroprotective effect on retinal ischemia
      reperfusion (RIR) injury through inhibition of PARP-1 activation. RIR was induced
      by transient elevation of intraocular pressure in rats. HRS (5 ml/kg) was
      administered peritoneally every day from the beginning of reperfusion in RIR rats
      until the rats were sacrificed. Retinal damage and cell death was determined
      using hematoxylin and eosin and terminal deoxynucleotidyl transferase dUTP nick
      end labeling staining. DNA oxidative stress was evaluated by immunofluorescence
      staining of 8-hydroxy-2-deoxyguanosine. In addition, the expression of PARP-1 and
      caspase-3 was investigated by western blot analysis and/or immunohistochemical
      staining. The results demonstrated that HRS administration improved morphological
      alterations and reduced apoptosis following RIR injury. Furthermore, the present
      study found that HRS alleviated DNA oxidation and PARP-1 overactivation in RIR
      rats. HRS can protect RIR injury by inhibition of PARP-1, which may be involved
      in DNA oxidative stress and caspase-3-mediated apoptosis.

PMID- 25954992
TI  - Pre- or post-treatment with ethanol and ethyl pyruvate results in distinct anti
      inflammatory responses of human lung epithelial cells triggered by interleukin-6.
AB  - Increased local and systemic levels of interleukin (IL)-6 are associated with
      inflammatory processes, including neutrophil infiltration of the alveolar space,
      resulting in lung injury. Our previous study demonstrated the beneficial anti
      inflammatory effects of acute exposure to ethanol (EtOH) in an acute in vivo
      model of inflammation. However, due to its side-effects, EtOH is not used
      clinically. In the present study, the effects of EtOH and ethyl pyruvate (EtP) as
      an alternative anti-inflammatory drug prior to and following application of an IL
      6 stimulus on cultured A549 lung epithelial cells were compared, and it was
      hypothesized that treatment with EtOH and EtP reduces the inflammatory potential
      of the A549 cells. Time- and dose-dependent release of IL-8 from the A549 cells
      was observed following stimulation with IL-6. The release of IL-8 from the A549
      cells was assessed following treatment with EtP (2.5-10 mM), sodium pyruvate
      (NaP; 10 mM) or EtOH (85-170 mM) for 1, 24 or 72 h, prior to and following IL-6
      stimulation. The adhesion capacities of neutrophils to the treated A549 cells,
      and the expression levels of cluster of differentiation (CD)54 by the epithelial
      cells were measured. Treatment of the A549 cells with either EtOH or EtP
      significantly reduced the IL-6-induced release of IL-8. This effect was observed
      in the pre- and post-stimulatory conditions, which is of therapeutic importance.
      Similar data was revealed regarding the IL-6-induced neutrophil adhesion to the
      treated A549 cells, in which pre- and post-treatment with EtOH or EtP decreased
      the adhesion capacity, however, the results were dependent on the duration of
      incubation. Incubation durations of 1 and 24 h decreased the adhesion rates of
      neutrophils to the stimulated A549 cells, however, the reduction was only
      significant at 72 h post-treatment. The expression of CD54 was reduced only
      following treatment for 24 h with either EtOH or EtP, prior to IL-6 stimulation.
      Therefore, EtOH and EtP reduced the inflammatory response of lung epithelial
      cells, and the potential of EtP to mimic EtOH was observed in the pre- and post
      treatment conditions.

PMID- 25954993
TI  - A novel intracerebral hemorrhage-induced rat model of neurogenic voiding
      dysfunction: Analysis of lower urinary tract function.
AB  - Neurogenic lower urinary tract dysfunction (NLUTD) is a major problem in patients
      with various neurological disorders, and may result in debilitating symptoms and
      serious complications, including chronic renal failure and recurrent urinary
      tract infections. Clinically, stroke is associated with voiding dysfunction.
      However, lower urinary tract function evaluation in an intracerebral hemorrhage
      (ICH) model has not, to the best of our knowledge, been reported. Therefore, in
      the present study, lower urinary tract function in ICH-induced rats was
      investigated and the results were compared with those obtained in normal rats.
      The effects of ICH on peripheral bladder function and central micturition centers
      [medial preoptic area, ventrolateral gray, pontaine micturition center and spinal
      cord (lumbar 4 (L4)-L5)] were also examined. Adult female Sprague-Dawley rats
      were divided into two groups: Control ICH-induced. Induction of ICH in the
      hippocampal CA1 region was performed using a stereotaxic frame and type IV
      collagenase. The effects of ICH on the central micturition centers were
      investigated by simultaneously determining the extent of neuronal activation (c
      Fos) and nerve growth factor (NGF) expression, and assessing voiding function
      (urodynamically using cystometry). The results revealed that induction of ICH
      significantly enhanced bladder contraction pressure and time, while
      simultaneously reducing voiding pressure and time. Furthermore, the c-Fos and NGF
      expression levels in the neuronal voiding centers were significantly increased in
      the rats with induced ICH as compared with the control rats. Therefore, this ICH
      induced NLUTD rat model may be a more appropriate method to analyze NLUTD in
      stroke patients than a cerebral infarction model, as the former more accurately
      reflects the nature of the hemorrhage in the two types of stroke.

PMID- 25954994
TI  - Microarray analysis of the aberrant microRNA expression pattern in gliomas of
      different grades.
AB  - Previous studies have focused on miRNA expression in brain gliomas. However, both
      the expression pattern of miRNAs in gliomas of different grades and various
      miRNAs involved in malignant progression of gliomas are poorly understood. In the
      present study, we used miRNA microarray-based screening to investigate the miRNA
      expression profile in gliomas, which was further verified by qRT-PCR in selected
      miRNAs. In total, we found 13 differentially expressed miRNAs between gliomas and
      their matched surrounding tissues. Among them, 12 miRNAs were upregulated and
      only one (miR-4489) was downregulated compared with the control. Furthermore, the
      lower expression level of miR-4489 was confirmed by qRT-PCR in 26 glioma samples.
      Our microarray result revealed 8, 9 and 15 aberrantly expressed miRNAs in gliomas
      of World Health Organization (WHO) grade II-IV, respectively. Gene Ontology (GO)
      and Pathway analysis indicated that target genes of the 13 miRNAs were
      significantly enriched in central nervous system- and tumor-related biological
      processes and signaling pathways. The dysregulated miRNAs identified in the
      present study contribute to the tumorigenesis and malignant progression of
      gliomas and may serve as useful markers for advanced glioma pathological grading
      and prognosis.

PMID- 25954995
TI  - Circulating microRNA-122, -21 and -223 as potential markers of liver injury
      following warm ischaemia and reperfusion in rats.
AB  - The liver enzymes aspartate aminotransferase (AST), alanine aminotransferase
      (ALT) and lactate dehydrogenase (LDH) are commonly used but not specific markers
      to quantify hepatic injury. In this in vivo study it was determined whether
      hepatic expression and serum levels of the microRNAs (miRNA) miR-122, -21 and 
      223 are altered and correlated with the release of liver enzymes after warm
      hepatic ischaemia and reperfusion (IR). Male Wistar rats were subjected to either
      45 min of partial (70%) hepatic ischaemia and 240 min of reperfusion (n=7) or
      sham operation (n=5). Expression levels of miR-122, -21 and -223 were analysed in
      serum and liver tissue by quantitative polymerase chain reaction and tested for
      correlation with serum activities of AST, ALT and LDH. The relative expression
      levels of circulating miR-122 increased after IR and correlated with the serum
      activity of AST, ALT and LDH. Neither increased serum level of miR-21 nor
      elevated relative hepatic expression of miR-223 correlated with the serum
      activity of liver enzymes. The hepatic expression of miR-122 was unaffected by
      IR. The correlation between circulating miR-122 expression levels and liver
      enzyme activity qualifies miR-122 as a potential biomarker of warm hepatic IR
      injury.

PMID- 25954996
TI  - Memory storage fidelity in the hippocampal circuit: the role of subregions and
      input statistics.
AB  - In the last decades a standard model regarding the function of the hippocampus in
      memory formation has been established and tested computationally. It has been
      argued that the CA3 region works as an auto-associative memory and that its
      recurrent fibers are the actual storing place of the memories. Furthermore, to
      work properly CA3 requires memory patterns that are mutually uncorrelated. It has
      been suggested that the dentate gyrus orthogonalizes the patterns before storage,
      a process known as pattern separation. In this study we review the model when
      random input patterns are presented for storage and investigate whether it is
      capable of storing patterns of more realistic entorhinal grid cell input.
      Surprisingly, we find that an auto-associative CA3 net is redundant for random
      inputs up to moderate noise levels and is only beneficial at high noise levels.
      When grid cell input is presented, auto-association is even harmful for memory
      performance at all levels. Furthermore, we find that Hebbian learning in the
      dentate gyrus does not support its function as a pattern separator. These
      findings challenge the standard framework and support an alternative view where
      the simpler EC-CA1-EC network is sufficient for memory storage. 

PMID- 25954997
TI  - Extended RAS and BRAF Mutation Analysis Using Next-Generation Sequencing.
AB  - Somatic mutations in KRAS, NRAS, and BRAF genes are related to resistance to anti
      EGFR antibodies in colorectal cancer. We have established an extended RAS and
      BRAF mutation assay using a next-generation sequencer to analyze these mutations.
      Multiplexed deep sequencing was performed to detect somatic mutations within
      KRAS, NRAS, and BRAF, including minor mutated components. We first validated the
      technical performance of the multiplexed deep sequencing using 10 normal DNA and
      20 formalin-fixed, paraffin-embedded (FFPE) tumor samples. To demonstrate the
      potential clinical utility of our assay, we profiled 100 FFPE tumor samples and
      15 plasma samples obtained from colorectal cancer patients. We used a variant
      calling approach based on a Poisson distribution. The distribution of the
      mutation-positive population was hypothesized to follow a Poisson distribution,
      and a mutation-positive status was defined as a value greater than the
      significance level of the error rate (alpha = 2 x 10(-5)). The cut-off value was
      determined to be the average error rate plus 7 standard deviations. Mutation
      analysis of 100 clinical FFPE tumor specimens was performed without any invalid
      cases. Mutations were detected at a frequency of 59% (59/100). KRAS mutation
      concordance between this assay and Scorpion-ARMS was 92% (92/100). DNA obtained
      from 15 plasma samples was also analyzed. KRAS and BRAF mutations were identified
      in both the plasma and tissue samples of 6 patients. The genetic screening assay
      using next-generation sequencer was validated for the detection of clinically
      relevant RAS and BRAF mutations using FFPE and liquid samples.

PMID- 25954998
TI  - Botulinum neurotoxin serotypes detected by electrochemical impedance
      spectroscopy.
AB  - Botulinum neurotoxin is one of the deadliest biological toxins known to mankind
      and is able to cause the debilitating disease botulism. The rapid detection of
      the different serotypes of botulinum neurotoxin is essential for both diagnosis
      of botulism and identifying the presence of toxin in potential cases of terrorism
      and food contamination. The modes of action of botulinum neurotoxins are well
      established in literature and differ for each serotype. The toxins are known to
      specifically cleave portions of the SNARE proteins SNAP-25 or VAMP; an
      interaction that can be monitored by electrochemical impedance spectroscopy. This
      study presents a SNAP-25 and a VAMP biosensors for detecting the activity of five
      botulinum neurotoxin serotypes (A-E) using electrochemical impedance
      spectroscopy. The biosensors are able to detect concentrations of toxins as low
      as 25 fg/mL, in a short time-frame compared with the current standard methods of
      detection. Both biosensors show greater specificity for their compatible
      serotypes compared with incompatible serotypes and denatured toxins. 

PMID- 25954999
TI  - Kruppel-like factor 4 modulates the migration and invasion of hepatoma cells by
      suppressing TIMP-1 and TIMP-2.
AB  - Kruppel-like factor 4 (KLF4) plays important roles in development, stemness and
      tumorigenesis; however limited information is available on the detailed function
      of KLF4 in hepatocellular carcinoma (HCC). The objective of the present study was
      to examine the functional roles of KLF4 in the metastasis of HCC cells. KLF4 was
      overexpressed and knocked down by lentiviral transduction method in highly
      metastatic HCC cells. KLF4 overexpression in HCC cells led to inhibition of cell
      migration and invasion. These inhibitory effects were associated with the
      upregulation of tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 by
      KLF4. Treatment with recombinant TIMP-1 decreased the migratory ability of HCC
      cells. Moreover, myeloperoxidase (MPO)-TIMP-1/TIMP-2 inactivator counteracted the
      KLF4-induced inhibition of cell migration/invasion. Consistently, KLF4 knockdown
      in HCC cells downregulated TIMP-1 and TIMP-2 expression, consequently promoting
      cell migration and invasion. Furthermore, we found that KLF4 regulated E-cadherin
      and epithelial-mesenchymal transition (EMT)-related proteins such as snail,
      vimentin and Bmi1 to modulate the cell migration ability. These results together
      demonstrated for the first time that KLF4 plays an important role in inhibiting
      the aggressiveness of HCC cells via upregulation of TIMP-1 and TIMP-2.

PMID- 25955001
TI  - Correction: Characterizing social media metrics of scholarly papers: the effect
      of document properties and collaboration patterns.

PMID- 25955000
TI  - High and fluctuating glucose levels increase the expression and secretion of
      interleukin-18 in mouse peritoneal macrophages.
AB  - Macrophages are involved in the progression of atherosclerosis by releasing pro
      inflammatory cytokines. High levels of interleukin (IL)-18 are associated with an
      increased risk of developing diabetes and atherosclerosis. The present study
      aimed to investigate the association between IL-18, and high and fluctuating
      glucose levels in mouse peritoneal macrophages (MPMs), and to assess the
      involvement of the c-Jun N-terminal kinase (JNK) pathway in this association. The
      MPMs were exposed to 4, 8, 16, 24 and 32 mM glucose for 6 h, which was alternated
      to either 4/24 mM glucose every 1.5 h for 6 h, or to 32 mM glucose for 3, 6, 12
      and 18 h. The expression and secretion levels of IL-18 were detected using
      reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and ELISA,
      respectively. High levels of glucose increased the expression and secretion
      levels of IL-18 in a dose-dependent manner (P<0.05, vs. 4 mM glucose). This
      increase was more important in the cells exposed to fluctuating 4/24 mM glucose
      every 1.5 h compared with the cells exposed to stable 24 mM glucose (RT-qPCR,
      0.78 +/- 0.05, vs. 0.66 +/- 0.07; ELISA, 188.23 +/- 20.32, vs. 143.16 +/- 13.07
      pg/ml; P<0.05). The expression and secretion levels of IL-18 increased 8 and 12 h
      following exposure to high-glucose, and then decreased at 18 h (P<0.05, vs. 3 h).
      Furthermore, SP600125, a JNK inhibitor, decreased the high-glucose-induced gene
      expression of IL-18 in a dose-dependent manner. Therefore, high and fluctuating
      levels of glucose may be associated with inflammation and diabetic
      atherosclerosis by regulating the expression levels of IL-18. The present study
      identified the JNK signaling pathway as one of the mechanisms underlying this
      association. Targeting IL-18 may be a novel therapeutic approach against diabetes
      associated atherosclerosis.

PMID- 25955002
TI  - Correction: MiRNA-615-5p Functions as a Tumor Suppressor in Pancreatic Ductal
      Adenocarcinoma by Targeting AKT2.

PMID- 25955003
TI  - Mechanoregulation of aortic valvular interstitial cell life and death.
AB  - Valvular interstitial cells (VICs) are the major cell type within aortic valve
      leaflets. VICs are able to exhibit a spectrum of phenotype characteristics
      including those of fibroblasts, smooth muscle cells, and myofibroblasts. VICs are
      responsible for valve maintenance and repair, yet excessive persistence of the
      myofibroblast phenotype is implicated in a number of valve diseases, including
      calcific aortic valve disease and fibrosis. Despite the prevalence of these
      diseases, the stimuli regulating the transition to the activated myofibroblast
      state and reversal to quiescent fibroblast and/or induction of apoptosis are not
      fully understood. The purpose of this article is to review in vitro studies that
      have contributed to the current understanding of mechanical regulation of VIC
      phenotype and fate. In particular, we have focused on studies utilizing advanced
      in vitro systems that allow modulation and measurement of cell tension and cell
      generated forces in two-dimensional and three-dimensional cultures. In addition,
      we discuss the importance of cell tension in phenotype modulation and how
      cytoskeletal tension may contribute to aggregation and calcification. Future
      directions of pharmaceutical development aimed at reducing VIC cytoskeletal
      tension are also highlighted.

PMID- 25955004
TI  - Relationships between melanocytes, mechanical properties and extracellular matrix
      composition in mouse heart valves.
AB  - Heart valves are complex structures composed of organized layers of extracellular
      matrix, and interstitial and overlying endothelial cells. In this article, we
      present the specific localization of a population of melanocytes within the
      murine heart valves at ages important for their post-natal development. In all
      stages analyzed in our study, melanocytes were found in high numbers populating
      the atrial aspect of the tricuspid and mitral leaflets. The pulmonary valve did
      not present melanocytes. To characterize a putative role for the valve
      melanocytes, the dynamic nanomechanical properties of tricuspid leaftets
      containing large numbers or no melanocytes were measured. The stiffness
      coefficient of hyperpigmented leaflets was higher (11.5 GPa) than the ones from
      wild-type (7.5 GPa) and hypopigmented (5.5 GPa) leaflets. These results suggest
      that melanocytes may contribute to the mechanical properties of the heart valves.
      The arrangement of extracellular matrix molecules such as Collagen I and Versican
      B is responsible for the mechanical characteristics of the leaflets. Melanocytes
      were found to reside primarily in areas of Versican B expression. The patterns of
      expression of Collagen I and Versican B were not, however, disrupted in hyper or
      hypopigmented leaflets. Melanocytes may affect other extracellular matrix
      molecules to alter the valves' microenvironment.

PMID- 25955005
TI  - The mechanobiology of drug-induced cardiac valve disease.
AB  - Drug-related adverse reactions leading to valve disease or valvulopathy were
      first identified in the 1960s. These were associated with patients taking anti
      migraine ergot-derivative drugs, anti-anorectics, anti-Parkinson's drugs, or
      other anti-depressant drugs. In general, these drugs have serotonergic,
      dopaminergic, or beta-adrenergic activity, being either agonists or reuptake
      inhibitors of the aforementioned neurotransmitter pathways. Recent work has
      focused on several possible mechanisms for valvulopathy, specifically
      highlighting the serotonin or 5-hydroxy-trypta-mine-2B (5-HT2B) receptor subtype
      and the 5-HT transporter as mediators that cause expression of myofibroblast
      phenotype, excessive cell proliferation, leading to valve fibrosis. Most of these
      studies and reviews, however, were not reported in the context of the mechanical
      environment of the valve, which by itself is an important factor in the
      initiation and progression of valve disease. It is also not known whether
      patients who have altered mechanical environments in their cardiovascular system,
      such as those who are hypertensive or have functional cardiac disease, such as
      ischemic ventricular dilation, or those who have an increased propensity for
      developing drug-induced valvulopathy. In the present review, we highlight the
      potential role of hemodynamics and the mechanical environment in influencing
      these drug-induced valvulopathies, focusing on serotonin-mediated disease and the
      need for further study of this topic.

PMID- 25955006
TI  - On the bending properties of porcine mitral, tricuspid, aortic, and pulmonary
      valve leaflets.
AB  - The atrioventricular valve leaflets (mitral and tricuspid) are different from the
      semilunar valve leaflets (aortic and pulmonary) in layered structure,
      ultrastructural constitution and organization, and leaflet thickness. These
      differences warrant a comparative look at the bending properties of the four
      types of leaflets. We found that the moment-curvature relationships in
      atrioventricular valves were stiffer than in semilunar valves, and the moment
      curvature relationships of the left-side valve leaflets were stiffer than their
      morphological analog of the right side. These trends were supported by the moment
      curvature curves and the flexural rigidity analysis (EI value decreased from
      mitral, tricuspid, aortic, to pulmonary leaflets). However, after taking away the
      geometric effect (moment of inertia I), the instantaneous effective bending
      modulus E showed a reversed trend. The overall trend of flexural rigidity (EI:
      mitral > tricuspid > aortic > pulmonary) might be correlated with the thickness
      variations among the four types of leaflets (thickness: mitral > tricuspid >
      aortic > pulmonary). The overall trend of the instantaneous effective bending
      modulus (E: mitral < tricuspid < aortic < pulmonary) might be correlated to the
      layered fibrous ultrastructures of the four types of leaflets, of which the
      fibers in mitral and tricuspid leaflets were less aligned, and the fibers in
      aortic and pulmonary leaflets were highly aligned. We also found that, for all
      types of leaflets, moment-curvature relationships are stiffer in against
      curvature (AC) bending than in with-curvature bending (WC), which implies that
      leaflets tend to flex toward their natural curvature and comply with blood flow.
      Lastly, we observed that the leaflets were stiffer in circumferential bending
      compared with radial bending, likely reflecting the physiological motion of the
      leaflets, i.e., more bending moment and movement were experienced in radial
      direction than circumferential direction. 

PMID- 25955008
TI  - A review of fluid-structure interaction simulations of prosthetic heart valves.
AB  - Dysfunctional natural heart valves are replaced with prosthetic heart valves
      through surgery. However, prosthetic valves are far from ideal. Bioprosthetic
      heart valves (BHVs) suffer from early calcification and structural damages.
      Mechanical heart valves (MHVs) are durable but highly thrombogenic and require
      lifelong anticoagulant treatment. These complications are believed to be related
      to nonphysiologic flow patterns created by these valves. Fluid-structure
      interaction (FSI) simulations are essential in revealing the hemodynamics of
      these valves. By combining the three-dimensional (3D) flow field obtained from
      realistic FSI simulations with platelet activation models, nonphysiologic flow
      patterns can be identified. In this review paper, state-of-the-art methods for
      simulating FSI in heart valves are reviewed, and the flow physics uncovered by
      FSI simulations are discussed. Finally, the limitations of current methods are
      discussed, and future research directions are proposed as follows: (1)
      incorporation of realistic, image-based ventricle and atrium geometries; (2)
      comparing MHV and BHV under similar conditions to identify nonphysiologic flow
      patterns; (3) developing better models to estimate platelet activation potential
      to be incorporated into the simulations; and (4) identifying the optimum
      placement of the valves in both mitral and aortic positions. 

PMID- 25955007
TI  - Fatigue damage of collagenous tissues: experiment, modeling and simulation
      studies.
AB  - Mechanical fatigue damage is a critical issue for soft tissues and tissue-derived
      materials, particularly for musculoskeletal and cardiovascular applications; yet,
      our understanding of the fatigue damage process is incomplete. Soft tissue
      fatigue experiments are often difficult and time-consuming to perform, which has
      hindered progress in this area. However, the recent development of soft-tissue
      fatigue-damage constitutive models has enabled simulation-based fatigue analyses
      of tissues under various conditions. Computational simulations facilitate highly
      controlled and quantitative analyses to study the distinct effects of various
      loading conditions and design features on tissue durability; thus, they are
      advantageous over complex fatigue experiments. Although significant work to
      calibrate the constitutive models from fatigue experiments and to validate
      predictability remains, further development in these areas will add to our
      knowledge of soft-tissue fatigue damage and will facilitate the design of durable
      treatments and devices. In this review, the experimental, modeling, and
      simulation efforts to study collagenous tissue fatigue damage are summarized and
      critically assessed. 

PMID- 25955009
TI  - Graphene nanoplatelet-reinforced silicone for the valvular prosthesis
      application.
AB  - Newly developed elastomer heart valves have been shown to better re-create the
      flow physics of native heart valves, resulting in preferable hemodynamic
      responses. This emergence has been motivated in part by the recent introduction
      of percutaneous valve approaches in the clinic. Unfortunately, elastomers such as
      silicone are prone to structural failure, which drastically limits their
      applicability the development of a valve prosthesis. To produce a mechanically
      more robust silicone substrate, we reinforced it with graphene nanoplatelets
      (GNPs). The nanoplatelets were introduced into a two-part silicone mixture and
      allowed to cure. Cytotoxicity and hemocompatibility tests revealed that the
      incorporation of GNPs did not adversely affect cell proliferation or augment
      adhesion of platelets on the surface of the composite materials. Static
      mechanical characterization by loading in the tensile direction subsequently
      showed no observable effect when graphene was utilized. However, cyclic tensile
      testing (0.05 Hz) demonstrated that silicone samples containing 250 mg graphene/L
      of uncured silicone significantly improved (p<0.05) material fatigue properties
      compared with silicone-only controls. This finding suggests that for the silicone
      graphene composite, static loads were principally transferred onto the matrix. On
      the other hand, in cyclic loading conditions, the GNPs were recruited effectively
      to delay failure of the bulk material. We conclude that application of GNPs to
      extend silicone durability is useful and warrants further evaluation at the
      trileaflet valve configuration.

PMID- 25955011
TI  - Mechanics of mitral valve edge-to-edge-repair and MitraClip procedure.
AB  - The edge-to-edge repair (ETER) technique has been used as a stand-alone
      procedure, or as a secondary procedure with ring annuloplasty for degenerative,
      functional mitral regurgitation, or for mitral regurgitation of other kinds of
      valvular etiologies. The percutaneous MitraClip technique based on ETER has been
      used in patients who are inoperable or at high surgical risk. However, adverse
      events such as residual mitral regurgitation, and clip detachment or fracture
      indicate that the mechanics underlying these procedures is not well understood.
      Therefore, current studies on mitral valve functionality and mechanics related to
      the ETER and MitraClip procedures are reviewed to improve the efficacy and safety
      of both procedures. Extensive in vivo, in vitro, and in silico studies related to
      ETER and MitraClip procedures along with MitraClip clinical trial results are
      presented and discussed herein. The ETER suture force and the mitral valve tissue
      mechanics and hemodynamics of each procedure are discussed. A quantitative
      understanding of the interplay of mitral valve components and as to biological
      response to the procedures remains challenging. Based on mitral valve mechanics,
      ETER or MitraClip therapy can be optimized to enhance repair efficacy and
      durability.

PMID- 25955012
TI  - Marrow stem cell differentiation for valvulogenesis via oscillatory flow and
      nicotine agonists: unusual suspects?
AB  - Fluid-induced oscillatory shear stress (OSS) and nicotine are known antagonists
      in cardiovascular disease. However, from a regenerative medicine standpoint, we
      hypothesized that these parameters may support the cell differentiation of bone
      marrow mesenchymal stem cells (BMMSCs) for engineering heart valves. In this
      study, OSS and nicotine (10-6M) were applied individually to BMMSCs in monolayer
      culture. In both cases, a significantly higher expression of CD31 was detected
      compared to corresponding controls (p<0.05). We interpret our findings to
      indicate that both OSS and nicotine independently support mesenchymal to
      endothelial transformation; however, the underlying mechanism for this
      transformation in terms of the cell cytoskeletal structure was entirely different
      between the two stimulants. In the case of OSS, F-actin filaments exhibited a
      stretching response and formed a preferential alignment with each other. However,
      in the nicotine-treated group, a clear increase was observed in the number of
      actin filaments present, which led to the maximum expression of CD31 in
      comparison to the OSS and control groups. From our findings, we speculate that
      while nicotine may stimulate an increase in the differentiation of BMMSCs to
      endothelial cells, OSS may play a greater role in cellular distribution and the
      eventual creation of a tissue engineered heart valve (TEHV) endothelium.

PMID- 25955010
TI  - Application of hydrogels in heart valve tissue engineering.
AB  - With an increasing number of patients requiring valve replacements, there is
      heightened interest in advancing heart valve tissue engineering (HVTE) to provide
      solutions to the many limitations of current surgical treatments. A variety of
      materials have been developed as scaffolds for HVTE including natural polymers,
      synthetic polymers, and decellularized valvular matrices. Among them,
      biocompatible hydrogels are generating growing interest. Natural hydrogels, such
      as collagen and fibrin, generally show good bioactivity but poor mechanical
      durability. Synthetic hydrogels, on the other hand, have tunable mechanical
      properties; however, appropriate cell-matrix interactions are difficult to
      obtain. Moreover, hydrogels can be used as cell carriers when the cellular
      component is seeded into the polymer meshes or decellularized valve scaffolds. In
      this review, we discuss current research strategies for HVTE with an emphasis on
      hydrogel applications. The physicochemical properties and fabrication methods of
      these hydrogels, as well as their mechanical properties and bioactivities are
      described. Performance of some hydrogels including in vitro evaluation using
      bioreactors and in vivo tests in different animal models are also discussed. For
      future HVTE, it will be compelling to examine how hydrogels can be constructed
      from composite materials to replicate mechanical properties and mimic biological
      functions of the native heart valve.

PMID- 25955013
TI  - Canine Mammary Tumours Are Affected by Frequent Copy Number Aberrations,
      including Amplification of MYC and Loss of PTEN.
AB  - BACKGROUND: Copy number aberrations frequently occur during the development of
      many cancers. Such events affect dosage of involved genes and may cause further
      genomic instability and progression of cancer. In this survey, canine SNP
      microarrays were used to study 117 canine mammary tumours from 69 dogs. RESULTS:
      We found a high occurrence of copy number aberrations in canine mammary tumours,
      losses being more frequent than gains. Increased frequency of aberrations and
      loss of heterozygosity were positively correlated with increased malignancy in
      terms of histopathological diagnosis. One of the most highly recurrently
      amplified regions harbored the MYC gene. PTEN was located to a frequently lost
      region and also homozygously deleted in five tumours. Thus, deregulation of these
      genes due to copy number aberrations appears to be an important event in canine
      mammary tumour development. Other potential contributors to canine mammary tumour
      pathogenesis are COL9A3, INPP5A, CYP2E1 and RB1. The present study also shows
      that a more detailed analysis of chromosomal aberrations associated with
      histopathological parameters may aid in identifying specific genes associated
      with canine mammary tumour progression. CONCLUSIONS: The high frequency of copy
      number aberrations is a prominent feature of canine mammary tumours as seen in
      other canine and human cancers. Our findings share several features with
      corresponding studies in human breast tumours and strengthen the dog as a
      suitable model organism for this disease.

PMID- 25955015
TI  - Increased anti-tumour activity by exosomes derived from doxorubicin-treated
      tumour cells via heat stress.
AB  - PURPOSE: Tumour-cell-derived exosomes (Exo) have been proposed as a new kind of
      drug carrier, and heat stress can promote release of exosomes from tumour cells.
      This study investigated the impact of heat stress on the quantity of doxorubicin
      in exosomes from the same number of doxorubicin-treated MFC-7 tumour cells and
      their anti-tumour effects. MATERIALS AND METHODS: Exosomes were isolated from
      phosphate-buffered saline (Exo), doxorubicin (Exo-Dox) or doxorubicin combined
      with heat-stress-treated (Exo-Dox-HS) MCF-7 cells. The content of doxorubicin in
      the exosomes was determined by flow cytometry. The effects of individual types of
      exosomes on the MCF-7 cell proliferation and apoptosis as well as the tumour
      growth were determined by MTT assay, flow cytometry and murine xenograft tumour
      modelling. RESULTS: We found that the amount of Exo-Dox-HS was higher than that
      of Exo-Dox from the same number of MCF-7 cells, and Exo-Dox-HS contained higher
      levels of doxorubicin than Exo-Dox from the same number of cells. Exo-Dox and Exo
      Dox-HS, but not Exo or 10 ug/mL doxorubicin, significantly inhibited the MCF-7
      cell proliferation and triggered MCF-7 cell apoptosis, associated with increased
      levels of cleaved caspase-3 and -8 and morphological changes in MCF-7 cells.
      Treatment with Exo-Dox and Exo-Dox-HS inhibited the growth of implanted breast
      tumours in mice. CONCLUSIONS: Our study indicated that heat stress increased the
      quantity of doxorubicin-containing exosomes from tumour cells, and enhanced the
      anti-tumour effect of exosomes from the doxorubicin-treated tumour cells. Our
      findings may aid in designing new strategies for cancer therapy by combination of
      chemotherapy and hyperthermia.

PMID- 25955014
TI  - Divergent roles of BECN1 in LC3 lipidation and autophagosomal function.
AB  - BECN1/Beclin 1 is regarded as a critical component in the class III
      phosphatidylinositol 3-kinase (PtdIns3K) complex to trigger autophagy in
      mammalian cells. Despite its significant role in a number of cellular and
      physiological processes, the exact function of BECN1 in autophagy remains
      controversial. Here we created a BECN1 knockout human cell line using the TALEN
      technique. Surprisingly, the complete loss of BECN1 had little effect on LC3
      (MAP1LC3B/LC3B) lipidation, and LC3B puncta resembling autophagosomes by
      fluorescence microscopy were still evident albeit significantly smaller than
      those in the wild-type cells. Electron microscopy (EM) analysis revealed that
      BECN1 deficiency led to malformed autophagosome-like structures containing
      multiple layers of membranes under amino acid starvation. We further confirmed
      that the PtdIns3K complex activity and autophagy flux were disrupted in BECN1(-/
      ) cells. Our results demonstrate the essential role of BECN1 in the functional
      formation of autophagosomes, but not in LC3B lipidation. 

PMID- 25955016
TI  - Heat and sound: focused ultrasound in the clinic.

PMID- 25955017
TI  - The tumor-suppressive microRNA-1/133a cluster targets PDE7A and inhibits cancer
      cell migration and invasion in endometrial cancer.
AB  - In developed countries, endometrial cancer (EC) is the most common malignancy
      among women. Unopposed estrogen therapy, obesity, nulliparity, diabetes mellitus
      and arterial hypertension have been linked to an increased risk of EC. However,
      the molecular mechanisms of EC oncogenesis and metastasis have not yet been fully
      elucidated. Our recent studies of microRNA (miRNA) expression signatures revealed
      that the microRNA-1/133a (miR-1/133a) cluster is frequently downregulated in
      various types of human cancers. However, the functional role of the miR-1/133a
      cluster in EC cells is still unknown. Thus, the aim of this study was to
      investigate the functional significance of the miR-1/133a cluster and its
      regulated molecular targets, with an emphasis on the contributions of miR-1/133a
      to EC oncogenesis and metastasis. We found that the expression levels of miR-1
      and miR-133a were significantly reduced in EC tissues. Moreover, restoration of
      mature miR-1 or miR-133a miRNAs significantly inhibited cancer cell migration and
      invasion, suggesting that these clustered miRNAs act as tumor suppressors.
      Prediction of miRNA targets revealed that phosphodiesterase 7A (PDE7A) was a
      potential target gene regulated by both miR-1 and miR-133a. PDE7A was confirmed
      to be overexpressed in EC clinical specimens and silencing of PDE7A significantly
      inhibited cancer cell migration and invasion. Our data demonstrated that
      downregulation of the miR-1/133a cluster promoted cancer cell migration and
      invasion via overexpression of PDE7A in EC cells. Elucidation of the molecular
      networks regulated by tumor-suppressive miRNAs will provide insights into the
      molecular mechanisms of EC oncogenesis and metastasis. 

PMID- 25955018
TI  - An Autocrine Cytokine/JAK/STAT-Signaling Induces Kynurenine Synthesis in
      Multidrug Resistant Human Cancer Cells.
AB  - BACKGROUND: Multidrug resistant cancer cells are hard to eradicate for the
      inefficacy of conventional anticancer drugs. Besides escaping the cytotoxic
      effects of chemotherapy, they also bypass the pro-immunogenic effects induced by
      anticancer drugs: indeed they are not well recognized by host dendritic cells and
      do not elicit a durable anti-tumor immunity. It has not yet been investigated
      whether multidrug resistant cells have a different ability to induce
      immunosuppression than chemosensitive ones. We addressed this issue in human and
      murine chemosensitive and multidrug resistant cancer cells. RESULTS: We found
      that the activity and expression of indoleamine 2,3-dioxygenase 1 (IDO1), which
      catalyzes the conversion of tryptophan into the immunosuppressive metabolite
      kynurenine, was higher in all the multidrug resistant cells analyzed and that
      IDO1 inhibition reduced the growth of drug-resistant tumors in immunocompetent
      animals. In chemoresistant cells the basal activity of JAK1/STAT1 and JAK1/STAT3
      signaling was higher, the STAT3 inhibitor PIAS3 was down-regulated, and the
      autocrine production of STAT3-target and IDO1-inducers cytokines IL-6, IL-4, IL
      1beta, IL-13, TNF-alpha and CD40L, was increased. The disruption of the JAK/STAT
      signaling lowered the IDO1 activity and reversed the kynurenine-induced pro
      immunosuppressive effects, as revealed by the restored proliferation of T
      lymphocytes in STAT-silenced chemoresistant cells. CONCLUSIONS: Our work shows
      that multidrug resistant cells have a stronger immunosuppressive attitude than
      chemosensitive cells, due to the constitutive activation of the JAK/STAT/IDO1
      axis, thus resulting chemo- and immune-evasive. Disrupting this axis may
      significantly improve the efficacy of chemo-immunotherapy protocols against
      resistant tumors.

PMID- 25955019
TI  - Reduction of metal artifact in single photon-counting computed tomography by
      spectral-driven iterative reconstruction technique.
AB  - PURPOSE: The exciting prospect of Spectral CT (SCT) using photon-counting
      detectors (PCD) will lead to new techniques in computed tomography (CT) that take
      advantage of the additional spectral information provided. We introduce a method
      to reduce metal artifact in X-ray tomography by incorporating knowledge obtained
      from SCT into a statistical iterative reconstruction scheme. We call our method
      Spectral-driven Iterative Reconstruction (SPIR). METHOD: The proposed algorithm
      consists of two main components: material decomposition and penalized maximum
      likelihood iterative reconstruction. In this study, the spectral data
      acquisitions with an energy-resolving PCD were simulated using a Monte-Carlo
      simulator based on EGSnrc C++ class library. A jaw phantom with a dental implant
      made of gold was used as an object in this study. A total of three dental implant
      shapes were simulated separately to test the influence of prior knowledge on the
      overall performance of the algorithm. The generated projection data was first
      decomposed into three basis functions: photoelectric absorption, Compton
      scattering and attenuation of gold. A pseudo-monochromatic sinogram was
      calculated and used as input in the reconstruction, while the spatial information
      of the gold implant was used as a prior. The results from the algorithm were
      assessed and benchmarked with state-of-the-art reconstruction methods. RESULTS:
      Decomposition results illustrate that gold implant of any shape can be
      distinguished from other components of the phantom. Additionally, the result from
      the penalized maximum likelihood iterative reconstruction shows that artifacts
      are significantly reduced in SPIR reconstructed slices in comparison to other
      known techniques, while at the same time details around the implant are
      preserved. Quantitatively, the SPIR algorithm best reflects the true attenuation
      value in comparison to other algorithms. CONCLUSION: It is demonstrated that the
      combination of the additional information from Spectral CT and statistical
      reconstruction can significantly improve image quality, especially streaking
      artifacts caused by the presence of materials with high atomic numbers.

PMID- 25955020
TI  - Episodic memories as building blocks of identity processing styles and life
      domains satisfaction: Examining need satisfaction and need for cognitive closure
      in memories.
AB  - The interconnection between identity and memory is widely accepted, but the
      processes underlying this association remain unclear. The present study examined
      how specific experiential components of self-defining memories relate to identity
      processing styles. We also investigated whether those relationships occurred in a
      domain-specific manner. Participants (n = 583) completed the Identity Style
      Inventory-3, which we adapted to measure identity in the school and friend
      domains, as well as scales assessing their friend and school satisfaction. They
      then described a memory related to each of these domains and rated the level of
      need satisfaction and need for cognitive closure characterising each memory.
      Results from structural equation modeling revealed that need satisfaction in the
      school-related memory was positively associated with an informational identity
      style at school and with satisfaction at school, whereas need satisfaction in the
      friend-related memory was positively associated with an informational identity
      style in both the school and friend domain, and with satisfaction with friends.
      In addition, need for cognitive closure in both the friend- and school-related
      memory was associated with normative friend and school identity processing
      styles. These findings reveal that specific experiential components of self
      defining memories are associated with certain identity processing styles.
      Furthermore, this relationship appears to be mostly domain-specific. 

PMID- 25955021
TI  - Novel Field Data on Phytoextraction: Pre-Cultivation With Salix Reduces Cadmium
      in Wheat Grains.
AB  - Cadmium (Cd) is a health hazard, and up to 43% of human Cd intake comes from
      wheat products, since Cd accumulates in wheat grains. Salix spp. are high
      accumulators of Cd and is suggested for Cd phytoextraction from agricultural
      soils. We demonstrate, in field, that Salix viminalis can remove Cd from
      agricultural soils and thereby reduce Cd accumulation in grains of wheat
      subsequently grown in a Salix-treated field. Four years of Salix cultivation
      reduce Cd concentration in the soil by up to 27% and in grains of the post
      cultivated wheat by up to 33%. The higher the plant density of the Salix, the
      greater the Cd removal from the soil and the lower the Cd concentration in the
      grains of post-cultivated wheat, the Cd reduction remaining stable several years
      after Salix cultivation. The effect occurred in both sandy and clayey soil and in
      winter and spring bread wheat cultivars. Already one year of Salix cultivation
      significantly decrease Cd in post grown wheat grains. With this field experiment
      we have demonstrated that phytoextraction can reduce accumulation of a pollutant
      in post-cultivated wheat and that phytoextraction has no other observed effect on
      post-cultivated crops than reduced uptake of the removed pollutant.

PMID- 25955022
TI  - Recovery of Cognitive Dysfunction via Orally Administered Redox-Polymer
      Nanotherapeutics in SAMP8 Mice.
AB  - Excessively generated reactive oxygen species are associated with age-related
      neurodegenerative diseases. We investigated whether scavenging of reactive oxygen
      species in the brain by orally administered redox nanoparticles, prepared by self
      assembly of redox polymers possessing antioxidant nitroxide radicals, facilitates
      the recovery of cognition in 17-week-old senescence-accelerated prone (SAMP8)
      mice. The redox polymer was delivered to the brain after oral administration of
      redox nanoparticles via a disintegration of the nanoparticles in the stomach and
      absorption of the redox polymer at small intestine to the blood. After treatment
      for one month, levels of oxidative stress in the brain of SAMP8 mice were
      remarkably reduced by treatment with redox nanoparticles, compared to that
      observed with low-molecular-weight nitroxide radicals, resulting in the
      amelioration of cognitive impairment with increased numbers of surviving neurons.
      Additionally, treatment by redox nanoparticles did not show any detectable
      toxicity. These findings indicate the potential of redox polymer nanotherapeutics
      for treatment of the neurodegenerative diseases. 

PMID- 25955023
TI  - Assessing the Probability that a Finding Is Genuine for Large-Scale Genetic
      Association Studies.
AB  - Genetic association studies routinely involve massive numbers of statistical
      tests accompanied by P-values. Whole genome sequencing technologies increased the
      potential number of tested variants to tens of millions. The more tests are
      performed, the smaller P-value is required to be deemed significant. However, a
      small P-value is not equivalent to small chances of a spurious finding and
      significance thresholds may fail to serve as efficient filters against false
      results. While the Bayesian approach can provide a direct assessment of the
      probability that a finding is spurious, its adoption in association studies has
      been slow, due in part to the ubiquity of P-values and the automated way they
      are, as a rule, produced by software packages. Attempts to design simple ways to
      convert an association P-value into the probability that a finding is spurious
      have been met with difficulties. The False Positive Report Probability (FPRP)
      method has gained increasing popularity. However, FPRP is not designed to
      estimate the probability for a particular finding, because it is defined for an
      entire region of hypothetical findings with P-values at least as small as the one
      observed for that finding. Here we propose a method that lets researchers extract
      probability that a finding is spurious directly from a P-value. Considering the
      counterpart of that probability, we term this method POFIG: the Probability that
      a Finding is Genuine. Our approach shares FPRP's simplicity, but gives a valid
      probability that a finding is spurious given a P-value. In addition to
      straightforward interpretation, POFIG has desirable statistical properties. The
      POFIG average across a set of tentative associations provides an estimated
      proportion of false discoveries in that set. POFIGs are easily combined across
      studies and are immune to multiple testing and selection bias. We illustrate an
      application of POFIG method via analysis of GWAS associations with Crohn's
      disease. 

PMID- 25955024
TI  - THYRPAN-TM Prototype: New System for Online Telemonitoring of Patients with
      Thyroid Carcinoma During the Treatment with a High Dose of Radioiodine.
AB  - BACKGROUND: Our team devised a real-time telemonitoring system (THYRPAN-TM) for
      measurement of the radiation exposure rate during the hospitalization of patients
      treated with high doses of radioiodine in the special premises with restricted
      access ("restricted area" [RA]). SUBJECTS AND METHODS: The THYRPAN-TM prototype
      was tested for stability, efficacy, and linearity in a 32-day measurement of a
      110 MBq (131)I source. Furthermore, it was tested on 15 patients with
      differentiated thyroid carcinoma who stayed in the RA for 3 days, following their
      radioiodine treatment. RESULTS: Minor deviation from the theoretical values was
      detected when the (131)I source was measured by the THYRPAN-TM, but only at the
      beginning of the measurement (7.20%). CONCLUSIONS: THYRPAN-TM is a stable, user
      friendly detection system for the measurement of the exposure rate following
      radioiodine administration. It enables the telemonitoring of patients, as well as
      real-time and online measurement of the whole-body burden of (131)I.

PMID- 25955025
TI  - Use of Anisotropy, 3D Segmented Atlas, and Computational Analysis to Identify
      Gray Matter Subcortical Lesions Common to Concussive Injury from Different Sites
      on the Cortex.
AB  - Traumatic brain injury (TBI) can occur anywhere along the cortical mantel. While
      the cortical contusions may be random and disparate in their locations, the
      clinical outcomes are often similar and difficult to explain. Thus a question
      that arises is, do concussions at different sites on the cortex affect similar
      subcortical brain regions? To address this question we used a fluid percussion
      model to concuss the right caudal or rostral cortices in rats. Five days later,
      diffusion tensor MRI data were acquired for indices of anisotropy (IA) for use in
      a novel method of analysis to detect changes in gray matter microarchitecture. IA
      values from over 20,000 voxels were registered into a 3D segmented, annotated rat
      atlas covering 150 brain areas. Comparisons between left and right hemispheres
      revealed a small population of subcortical sites with altered IA values. Rostral
      and caudal concussions were of striking similarity in the impacted subcortical
      locations, particularly the central nucleus of the amygdala, laterodorsal
      thalamus, and hippocampal complex. Subsequent immunohistochemical analysis of
      these sites showed significant neuroinflammation. This study presents three
      significant findings that advance our understanding and evaluation of TBI: 1) the
      introduction of a new method to identify highly localized disturbances in
      discrete gray matter, subcortical brain nuclei without postmortem histology, 2)
      the use of this method to demonstrate that separate injuries to the rostral and
      caudal cortex produce the same subcortical, disturbances, and 3) the central
      nucleus of the amygdala, critical in the regulation of emotion, is vulnerable to
      concussion. 

PMID- 25955026
TI  - The association of platelet count with clinicopathological significance and
      prognosis in renal cell carcinoma: a systematic review and meta-analysis.
AB  - OBJECTIVE: Elevated platelet count (PC), a measure of systemic inflammatory
      response, is inconsistently reported to be associated with poor prognosis in
      patients with renal cell carcinoma (RCC). We conducted a systematic review and
      meta-analysis to clarify the significance of PC in RCC prognosis. METHODS:
      PubMed, Embase, and Web of Science databases were searched to identify eligible
      studies to evaluate the associations of PC with patient survival and
      clinicopathological features of RCC. RESULTS: We analyzed 25 studies including
      11,458 patients in the meta-analysis and categorized the included articles into
      three groups based on RCC stage. An elevated PC level was associated with poor
      overall survival (OS, hazard ratio [HR] 2.24, 95% confidence interval [CI] 1.87
      2.67, P<0.001) and cancer-specific survival (CSS, HR 2.59, 95% CI 1.92-3.48,
      P<0.001) when all stages were examined together; with poor CSS (HR 5.09, 95% CI
      2.41-10.73, P<0.001) and recurrence-free survival (HR 6.68, 95% CI 3.35-13.34,
      P<0.001) for localized RCC; with poor OS (HR 2.00, 95% CI 1.75-2.28, P<0.001) for
      metastatic RCC; and with poor OS (HR 2.05, 95% CI 1.04-4.03, P = 0.038), CSS (HR
      3.38, 95% CI 1.86-6.15, P<0.001), and PFS (HR 2.97, 95% CI 1.47-6.00, P = 0.002)
      for clear cell RCC. Furthermore, an elevated PC level was significantly
      associated with TNM stage (OR 3.11, 95% CI 1.59-6.06, P = 0.001), pathological T
      stage (OR 3.13, 95% CI 2.60-3.77, P<0.001), lymph node metastasis (OR 4.01, 95%
      CI 2.99-5.37, P<0.001), distant metastasis (OR 3.85, 95% CI 2.46-6.04, P<0.001),
      Fuhrman grade (OR 3.70, 95% CI 3.00-4.56, P<0.001), tumor size (OR 4.69, 95% CI
      2.78-7.91, P<0.001) and Eastern Cooperative Oncology Group score (OR 5.50, 95% CI
      3.26-9.28, P<0.001). CONCLUSION: An elevated PC level implied poor prognosis in
      patients with RCC and could serve as a readily available biomarker for managing
      this disease.

PMID- 25955027
TI  - Initiation and characterization of small cell lung cancer patient-derived
      xenografts from ultrasound-guided transbronchial needle aspirates.
AB  - Small cell lung cancer (SCLC) is a devastating disease with limited treatment
      options. Due to its early metastatic nature and rapid growth, surgical resection
      is rare. Standard of care treatment regimens remain largely unchanged since the
      1980's, and five-year survival lingers near 5%. Patient-derived xenograft (PDX)
      models have been established for other tumor types, amplifying material for
      research and serving as models for preclinical experimentation; however, limited
      availability of primary tissue has curtailed development of these models for
      SCLC. The objective of this study was to establish PDX models from commonly
      collected fine needle aspirate biopsies of primary SCLC tumors, and to assess
      their utility as research models of primary SCLC tumors. These transbronchial
      needle aspirates efficiently engrafted as xenografts, and tumor histomorphology
      was similar to primary tumors. Resulting tumors were further characterized by H&E
      and immunohistochemistry, cryopreserved, and used to propagate tumor-bearing mice
      for the evaluation of standard of care chemotherapy regimens, to assess their
      utility as models for tumors in SCLC patients. When treated with Cisplatin and
      Etoposide, tumor-bearing mice responded similarly to patients from whom the
      tumors originated. Here, we demonstrate that PDX tumor models can be efficiently
      established from primary SCLC transbronchial needle aspirates, even after
      overnight shipping, and that resulting xenograft tumors are similar to matched
      primary tumors in cancer patients by both histology and chemo-sensitivity. This
      method enables physicians at non-research institutions to collaboratively
      contribute to the rapid establishment of extensive PDX collections of SCLC,
      enabling experimentation with clinically relevant tissues and development of
      improved therapies for SCLC patients. 

PMID- 25955029
TI  - Size-dependent active effect of cadmium telluride quantum dots on luminol
      potassium periodate chemiluminescence system for levodopa detection.
AB  - It was found that cadmium telluride (CdTe) quantum dots (QDs) with different
      sizes can have a great sensitizing effect on chemiluminescence (CL) emission from
      luminol-potassium periodate (KIO4) system. Levodopa, a widely prescribed drug in
      the treatment of Parkinson's disease, could inhibit luminol-KIO4-CdTe QDs CL
      reaction in alkaline solution. The inhibited CL intensity was proportional to the
      concentration of levodopa in the range from 8.0 nM to 10.0 MUM. The detection
      limit was 3.8 nM. This method has been successfully applied to determine levodopa
      in pharmaceutical preparation and human urine and plasma samples with recoveries
      of 94.1-105.4%. This was the first work for inhibition effect determination of
      levodopa using a QD-based CL method. 

PMID- 25955028
TI  - Nano-ropinirole for the management of Parkinsonism: blood-brain pharmacokinetics
      and carrier localization.
AB  - AIM: The aim of this study was to investigate the brain targeting potential of
      chitosan-coated oil in water nanoemulsions (CSNE(ROP)) delivered intranasally in
      haloperidol-induced Parkinson's disease rat models. METHODS: Chitosan-coated
      nanoemulsion (CSNE(ROP)) was developed through aqueous titration followed by a
      high pressure homogenization method. RESULTS: Gamma-scintigraphy study showed a
      significantly high mucoadhesive potential of CSNE(ROP) and least for conventional
      and homogenized formulations. Confocal study showed deep localization of
      formulations in the brain confirming the permeation potential of CSNE(ROP).
      Pharmacokinetic results of CSNE(ROP) in Wistar rat brain and plasma showed a
      significantly high (p** < 0.005) AUC0->24 and amplified Cmax over i.v treatment
      group. Neurobehavioral activity (rotarod and swim tests) and biochemical
      parameters (glutathion, TBARS and SOD) corroborated well with the pharmacokinetic
      results. The order of dopamine recovery in haloperidol-induced Wistar rats was
      found to be (i.n)CSNEROP group>(i.n)SolnROP group>(i.v)SolnROP group>haloperidol
      group. CONCLUSIONS: Finally, the investigation demonstrated that intranasal
      delivery of mucoadhesive nanocarrier might play as a potential candidate in the
      management of Parkinson's disease and related brain disorders.

PMID- 25955032
TI  - Fabrication mechanism and structural characteristics of the ternary aggregates by
      lactoferrin, pectin, and (-)-epigallocatechin gallate using multispectroscopic
      methods.
AB  - The ternary aggregates were fabricated by lactoferrin (LF), pectin (high
      methylated pectin (HMP)/low methylated pectin (LMP)), and (-)-epigallocatechin
      gallate (EGCG) through three different fabrication methods at pH 5.0. The
      turbidity, particle size, and zeta-potential of ternary aggregates were
      influenced by the types of pectin, the concentration of EGCG, and fabrication
      methods. The fluorescence intensity of LF decreased with an increase in EGCG
      concentration for all ternary aggregates. Far-UV circular dichroism results
      indicated that EGCG could alter the secondary structure of LF with an increase in
      the proportion of beta-sheet structure at the cost of unordered coil structure.
      According to near-UV circular dichroism results, EGCG could also modulate the
      tertiary structure of LF at the presence of pectin. In addition, EGCG could
      increase the viscoelasticity of the ternary aggregates with HMP, leading to
      better stability of the ternary aggregates. An opposite result was observed for
      the ternary aggregates with LMP. These findings should provide an insight into
      the fabrication mechanism and applications of ternary aggregates formed by
      protein, polysaccharide, and polyphenol in the food, pharmaceutical, and cosmetic
      industries. 

PMID- 25955030
TI  - Molecular heterogeneity in a patient-derived glioblastoma xenoline is regulated
      by different cancer stem cell populations.
AB  - Malignant glioblastoma (GBM) is a highly aggressive brain tumor with a dismal
      prognosis and limited therapeutic options. Genomic profiling of GBM samples has
      identified four molecular subtypes (Proneural, Neural, Classical and
      Mesenchymal), which may arise from different glioblastoma stem-like cell (GSC)
      populations. We previously showed that adherent cultures of GSCs grown on laminin
      coated plates (Ad-GSCs) and spheroid cultures of GSCs (Sp-GSCs) had high
      expression of stem cell markers (CD133, Sox2 and Nestin), but low expression of
      differentiation markers (betaIII-tubulin and glial fibrillary acid protein). In
      the present study, we characterized GBM tumors produced by subcutaneous and
      intracranial injection of Ad-GSCs and Sp-GSCs isolated from a patient-derived
      xenoline. Although they formed tumors with identical histological features, gene
      expression analysis revealed that xenografts of Sp-GSCs had a Classical molecular
      subtype similar to that of bulk tumor cells. In contrast xenografts of Ad-GSCs
      expressed a Mesenchymal gene signature. Adherent GSC-derived xenografts had high
      STAT3 and ANGPTL4 expression, and enrichment for stem cell markers,
      transcriptional networks and pro-angiogenic markers characteristic of the
      Mesenchymal subtype. Examination of clinical samples from GBM patients showed
      that STAT3 expression was directly correlated with ANGPTL4 expression, and that
      increased expression of these genes correlated with poor patient survival and
      performance. A pharmacological STAT3 inhibitor abrogated STAT3 binding to the
      ANGPTL4 promoter and exhibited anticancer activity in vivo. Therefore, Ad-GSCs
      and Sp-GSCs produced histologically identical tumors with different gene
      expression patterns, and a STAT3/ANGPTL4 pathway is identified in glioblastoma
      that may serve as a target for therapeutic intervention. 

PMID- 25955033
TI  - Response of the Rumen Microbiota of Sika Deer (Cervus nippon) Fed Different
      Concentrations of Tannin Rich Plants.
AB  - High throughput sequencing was used to examine the rumen microbiota of sika deer
      fed high (OLH) and low concentration (OLL) of tannin rich oak leaves. The results
      showed that Prevotella spp. were the most dominant bacteria. The most predominant
      methanogens were the members of the order Methanoplasmatales. The dominant rumen
      protozoa were Entodinium longinucleatum, Eudiplodinium maggii, and Epidinium
      caudatum, and the fungal communities were mostly represented by Piromyces spp.
      Moreover, the relative abundance of Pseudobutyrivibrio spp. (P=0.026),
      unidentified bacteria (P=0.028), and Prevotella spp. (P=0.022) was lower in the
      OLH group than in the OLL group. The concentration of propionate in the OLH group
      was greater than in the OLL group (P=0.006). Patterns of relationships showed
      that methanogens belonging to the order Methanoplasmatales were negatively
      correlated with Treponema spp., Ent. Longinucleatum, and acetate. Methanosphaera
      stadtmanae was positively correlated to propionate, while Methanobrevibacter
      ruminantium was negatively associated with Methanobrevibacter thaueri and
      Methanobrevibacter millerae. Tannins altered the rumen microbes and fermentation
      patterns. However, the response of the entire rumen microbiota and the
      relationship between rumen microorganisms and the fermentation parameters were
      not fully understood. 

PMID- 25955031
TI  - The administration of Fructus Schisandrae attenuates dexamethasone-induced muscle
      atrophy in mice.
AB  - In the present study, we aimed to determine whether ethanol extracts of Fructus
      Schisandrae (FS), the dried fruit of Schizandra chinensis Baillon, mitigates the
      development of dexamethasone-induced muscle atrophy. Adult SPF/VAT outbred
      CrljOri:CD1 (ICR) mice were either treated with dexamethasone to induce muscle
      atrophy. Some mice were treated with various concentrations of FS or
      oxymetholone, a 17alpha-alkylated anabolic-androgenic steroid. Muscle thickness
      and weight, calf muscle strength, and serum creatine and creatine kinase (CK)
      levels were then measured. The administration of FS attenuated the decrease in
      calf thickness, gastrocnemius muscle thickness, muscle strength and weight, fiber
      diameter and serum lactate dehydrogenase levels in the gastrocnemius muscle
      bundles which was induced by dexamethasone in a dose-dependent manner. Treatment
      with FS also prevented the dexamethasone-induced increase in serum creatine and
      creatine kinase levels, histopathological muscle fiber microvacuolation and
      fibrosis, and the immunoreactivity of muscle fibers for nitrotyrosine, 4
      hydroxynonenal, inducible nitric oxide synthase and myostatin. In addition, the
      destruction of the gastrocnemius antioxidant defense system was also inhibited by
      the administration of FS in a dose-dependent manner. FS downregulated the mRNA
      expression of atrogin-1 and muscle ring-finger protein-1 (involved in muscle
      protein degradation), myostatin (a potent negative regulator of muscle growth)
      and sirtuin 1 (a representative inhibitor of muscle regeneration), but
      upregulated the mRNA expression of phosphatidylinositol 3-kinase, Akt1, adenosine
      A1 receptor and transient receptor potential cation channel subfamily V member 4,
      involved in muscle growth and the activation of protein synthesis. The overall
      effects of treatment with 500 mg/kg FS were comparable to those observed
      following treatment with 50 mg/kg oxymetholone. The results from the present
      study support the hypothesis that FS has a favorable ameliorating effect on
      muscle atrophy induced by dexamethasone, by exerting anti-inflammatory and
      antioxidant effects on muscle fibers, which may be due to an increase in protein
      synthesis and a decrease in protein degradation.

PMID- 25955035
TI  - Resistive switching and polarization reversal of hydrothermal-method-grown
      undoped zinc oxide nanorods by using scanning probe microscopy techniques.
AB  - This paper reports the localized electrical, polarization reversal, and
      piezoelectric properties of the individual hexagonal ZnO nanorods, which are
      grown via the hydrothermal method and textured with [0001] orientation. The
      studies are conducted with conductive atomic force microscopy (c-AFM) and
      piezoresponse force microscopy (PFM) techniques. The correlation between the
      resistance switching and polarization reversal is discussed. The c-AFM results
      show that there is less variation on the set or reset voltage in nanorod samples,
      compared to that of the ZnO thin film. With increasing aspect ratio of the
      nanorods, both set and reset voltages are decreased. The nanorods with low aspect
      ratio show unipolar resistance switching, whereas both unipolar and bipolar
      resistance switching are observed when the aspect ratio is larger than 0.26. The
      PFM results further show the ferroelectric-like property in the nanorods.
      Comparing with that of the ZnO thin film, the enhanced piezoresponse in the
      nanorods can be attributed to the size effect. In addition, the piezoresponse
      force spectroscopy (PFS) experiments are conducted in ambient air, synthetic air,
      and argon gas. It shows that the depolarization field in the nanorod may be due
      to the moisture in the environment; moreover, the increased piezoresponse may
      relate to the absence of oxygen in the environment. It is also shown that the
      piezoelectric responses increase nonlinearly with the aspect ratio of the
      nanorods. By comparing the piezoresponse hysteresis loops obtained from the
      nanorod samples of as-grown, air-annealed and vacuum-annealed, it is found that
      the oxygen vacancies are the origin of the polarization reversal in ZnO nanorods.
      Finally, the tradeoff between the electrical and ferroelectric-like properties is
      also observed. 

PMID- 25955034
TI  - MAF2 Is Regulated by Temperature-Dependent Splicing and Represses Flowering at
      Low Temperatures in Parallel with FLM.
AB  - Plants enter their reproductive phase when the environmental conditions are
      favourable for the successful production of progeny. The transition from
      vegetative to reproductive phase is influenced by several environmental factors
      including ambient temperature. In the model plant Arabidopsis thaliana, SHORT
      VEGETATIVE PHASE (SVP) is critical for this pathway; svp mutants cannot modify
      their flowering time in response to ambient temperature. SVP encodes a MADS-box
      transcription factor that directly represses genes that promote flowering. SVP
      binds DNA in complexes with other MADS-box transcription factors, including
      FLOWERING LOCUS M (FLM), which acts with SVP to repress the floral transition at
      low temperatures. Small temperature changes post-transcriptionally regulate FLM
      through temperature-dependent alternative splicing (TD-AS). As ambient
      temperature increases, the predominant FLM splice isoform shifts to encode a
      protein incapable of exerting a repressive effect on flowering. Here we
      characterize a closely related MADS-box transcription factor, MADS AFFECTING
      FLOWERING2 (MAF2), which has independently evolved TD-AS. At low temperatures the
      most abundant MAF2 splice variant encodes a protein that interacts with SVP to
      repress flowering. At increased temperature the relative abundance of splice
      isoforms shifts in favour of an intron-retaining variant that introduces a
      premature termination codon. We show that this isoform encodes a protein that
      cannot interact with SVP or repress flowering. At lower temperatures MAF2 and SVP
      repress flowering in parallel with FLM and SVP, providing an additional input to
      sense ambient temperature for the control of flowering. 

PMID- 25955037
TI  - Anomalous diffusion and griffiths effects near the many-body localization
      transition.
AB  - We explore the high-temperature dynamics of the disordered, one-dimensional XXZ
      model near the many-body localization (MBL) transition, focusing on the
      delocalized (i.e., "metallic") phase. In the vicinity of the transition, we find
      that this phase has the following properties: (i) local magnetization
      fluctuations relax subdiffusively; (ii) the ac conductivity vanishes near zero
      frequency as a power law; and (iii) the distribution of resistivities becomes
      increasingly broad at low frequencies, approaching a power law in the zero
      frequency limit. We argue that these effects can be understood in a unified way
      if the metallic phase near the MBL transition is a quantum Griffiths phase. We
      establish scaling relations between the associated exponents, assuming a scaling
      form of the spin-diffusion propagator. A phenomenological classical resistor
      capacitor model captures all the essential features. 

PMID- 25955036
TI  - Comparison of CT-Determined Pulmonary Artery Diameter, Aortic Diameter, and Their
      Ratio in Healthy and Diverse Clinical Conditions.
AB  - BACKGROUND: The main pulmonary artery diameter (mPA), aortic diameter (Ao), and
      the mPA/Ao ratio, easily measured using chest computed tomography (CT), provide
      information that enables the diagnosis and evaluation of cardiopulmonary
      diseases. Here, we used CT to determine the sex- and age-specific distribution of
      normal reference values for mPA, Ao, and mPA/Ao ratio in an adult Korean
      population. METHODS: Data from non-contrast, ECG-gated, coronary-calcium-scoring
      CT images of 2,547 individuals who visited the Health Screening Center of the
      Severance Hospital were analyzed. Healthy individuals (n = 813) included those
      who do not have hypertension, diabetes, asthma, obstructive lung disease,
      ischemic heart disease, stroke, smoking, obesity, and abnormal CT findings. Both
      mPA and Ao were measured at the level of bifurcation of the main pulmonary
      artery. RESULTS: The mean mPA and Ao were 25.9 mm and 30.0 mm in healthy
      participants, respectively, while the mean mPA/Ao ratio was 0.87. Medical
      conditions associated with a larger mPA were male, obesity, smoking history,
      hypertension, and diabetes. A larger mPA/Ao ratio was associated with female, the
      obese, non-smoker, normotensive, and normal serum level of lipids, while a
      smaller mPA/Ao ratio was associated with older age. In healthy individuals, the
      90th percentile sex-specific mPA, Ao, and mPA/Ao ratio were, 31.3 mm (95% CI 29.9
      32.2), 36.8 mm (95% CI 35.7-37.5), and 1.05 (95% CI 0.99-1.07) in males, and 29.6
      mm (95% CI 29.1-30.2), 34.5 mm (95% CI 34.1-34.9), and 1.03 (95% CI 1.02-1.06) in
      females, respectively. CONCLUSION: In the Korean population, the mean mPA
      reference values in male and female were 26.5 mm and 25.8 mm, respectively, while
      the mean mPA/Ao ratio was 0.87. These values were influenced by a variety of
      underlying medical conditions.

PMID- 25955038
TI  - Evaluating convex roof entanglement measures.
AB  - We show a powerful method to compute entanglement measures based on convex roof
      constructions. In particular, our method is applicable to measures that, for pure
      states, can be written as low order polynomials of operator expectation values.
      We show how to compute the linear entropy of entanglement, the linear
      entanglement of assistance, and a bound on the dimension of the entanglement for
      bipartite systems. We discuss how to obtain the convex roof of the three-tangle
      for three-qubit states. We also show how to calculate the linear entropy of
      entanglement and the quantum Fisher information based on partial information or
      device independent information. We demonstrate the usefulness of our method by
      concrete examples. 

PMID- 25955039
TI  - Maximally nonlocal theories cannot be maximally random.
AB  - Correlations that violate a Bell inequality are said to be nonlocal; i.e., they
      do not admit a local and deterministic explanation. Great effort has been devoted
      to study how the amount of nonlocality (as measured by a Bell inequality
      violation) serves to quantify the amount of randomness present in observed
      correlations. In this work we reverse this research program and ask what do the
      randomness certification capabilities of a theory tell us about the nonlocality
      of that theory. We find that, contrary to initial intuition, maximal randomness
      certification cannot occur in maximally nonlocal theories. We go on and show that
      quantum theory, in contrast, permits certification of maximal randomness in all
      dichotomic scenarios. We hence pose the question of whether quantum theory is
      optimal for randomness; i.e., is it the most nonlocal theory that allows maximal
      randomness certification? We answer this question in the negative by identifying
      a larger-than-quantum set of correlations capable of this feat. Not only are
      these results relevant to understanding quantum mechanics' fundamental features,
      but also put fundamental restrictions on device-independent protocols based on
      the no-signaling principle. 

PMID- 25955040
TI  - Quantum de Finetti Theorem under Fully-One-Way Adaptive Measurements.
AB  - We prove a version of the quantum de Finetti theorem: permutation-invariant
      quantum states are well approximated as a probabilistic mixture of multifold
      product states. The approximation is measured by distinguishability under
      measurements that are implementable by fully-one-way local operations and
      classical communication (LOCC). Our result strengthens Brandao and Harrow's de
      Finetti theorem where a kind of partially-one-way LOCC measurements was used for
      measuring the approximation, with essentially the same error bound. As main
      applications, we show (i) a quasipolynomial-time algorithm which detects
      multipartite entanglement with an amount larger than an arbitrarily small
      constant (measured with a variant of the relative entropy of entanglement), and
      (ii) a proof that in quantum Merlin-Arthur proof systems, polynomially many
      provers are not more powerful than a single prover when the verifier is
      restricted to one-way LOCC operations. 

PMID- 25955041
TI  - Constraints on new gravitylike forces in the nanometer range.
AB  - We report on a new constraint on gravitylike short-range forces, in which the
      interaction charge is mass, obtained by measuring the angular distribution of 5 A
      neutrons scattering off atomic xenon gas. Around 10^{7} scattering events were
      collected at the 40 m small angle neutron scattering beam line located at the
      HANARO research reactor of the Korean Atomic Energy Research Institute. The
      extracted coupling strengths of new forces in the Yukawa-type parametrization are
      g[over ^]^{2}=(0.2+/-6.8+/-2.0)*10^{-15}  GeV^{-2} and g[over ^]^{2}=(-5.3+/
      9.0_{-2.8}^{+2.7})*10^{-17}  GeV^{-2} for interaction ranges of 0.1 and 1.0 nm,
      respectively. These strengths correspond to 95% confidence level limits of
      g^{2}<(1.4+/-0.2)*10^{-14}  GeV^{-2} and g^{2}<(1.3+/-0.2)*10^{-16}  GeV^{-2},
      improving the current limits for interaction ranges between 4 and 0.04 nm by a
      factor of up to 10. 

PMID- 25955043
TI  - Modeling the Dynamics of Tidally Interacting Binary Neutron Stars up to the
      Merger.
AB  - The data analysis of the gravitational wave signals emitted by coalescing neutron
      star binaries requires the availability of an accurate analytical representation
      of the dynamics and waveforms of these systems. We propose an effective-one-body
      model that describes the general relativistic dynamics of neutron star binaries
      from the early inspiral up to the merger. Our effective-one-body model
      incorporates an enhanced attractive tidal potential motivated by recent
      analytical advances in the post-Newtonian and gravitational self-force
      description of relativistic tidal interactions. No fitting parameters are
      introduced for the description of tidal interaction in the late, strong-field
      dynamics. We compare the model energetics and the gravitational wave phasing with
      new high-resolution multiorbit numerical relativity simulations of equal-mass
      configurations with different equations of state. We find agreement within the
      uncertainty of the numerical data for all configurations. Our model is the first
      semianalytical model that captures the tidal amplification effects close to
      merger. It thereby provides the most accurate analytical representation of binary
      neutron star dynamics and waveforms currently available. 

PMID- 25955042
TI  - Observation of Parametric Instability in Advanced LIGO.
AB  - Parametric instabilities have long been studied as a potentially limiting effect
      in high-power interferometric gravitational wave detectors. Until now, however,
      these instabilities have never been observed in a kilometer-scale interferometer.
      In this Letter, we describe the first observation of parametric instability in a
      gravitational wave detector, and the means by which it has been removed as a
      barrier to progress. 

PMID- 25955044
TI  - Searching for dark matter and variation of fundamental constants with laser and
      maser interferometry.
AB  - Any slight variations in the fundamental constants of nature, which may be
      induced by dark matter or some yet-to-be-discovered cosmic field, would
      characteristically alter the phase of a light beam inside an interferometer,
      which can be measured extremely precisely. Laser and maser interferometry may be
      applied to searches for the linear-in-time drift of the fundamental constants,
      detection of topological defect dark matter through transient-in-time effects,
      and for a relic, coherently oscillating condensate, which consists of scalar dark
      matter fields, through oscillating effects. Our proposed experiments require
      either minor or no modifications of existing apparatus, and offer extensive reach
      into important and unconstrained spaces of physical parameters. 

PMID- 25955045
TI  - Massless mode and positivity violation in hot QCD.
AB  - We calculate the quark self-energy at one-loop level at high temperature, taking
      into account contributions from both the (chromo)electric scale gT and the
      (chromo)magnetic scale g^{2}T. While reproducing standard massive excitations due
      to the electric scale, we uncover a novel massless excitation ascribable to the
      magnetic scale. The residue of this massless excitation is nonpositive at all
      temperatures, which consequently gives rise to positivity violation in the quark
      spectral functions. This demonstrates the profound impact of confinement effects
      on thermal quark collective excitations, which manifest genuine long-range
      correlations in the system. 

PMID- 25955047
TI  - Nonstandard semileptonic hyperon decays.
AB  - We investigate the discovery potential of semileptonic hyperon decays in terms of
      searches of new physics at teraelectronvolt scales. These decays are controlled
      by a small SU(3)-flavor breaking parameter that allows for systematic expansions
      and accurate predictions in terms of a reduced dependence on hadronic form
      factors. We find that muonic modes are very sensitive to nonstandard scalar and
      tensor contributions and demonstrate that these could provide a powerful synergy
      with direct searches of new physics at the LHC. 

PMID- 25955049
TI  - Channel-resolved above-threshold double ionization of acetylene.
AB  - We experimentally investigate the channel-resolved above-threshold double
      ionization (ATDI) of acetylene in the multiphoton regime using an ultraviolet
      femtosecond laser pulse centered at 395 nm by measuring all the ejected electrons
      and ions in coincidence. As compared to the sequential process, diagonal lines in
      the electron-electron joint energy spectrum are observed for the nonsequential
      ATDI owing to the correlative sharing of the absorbed multiphoton energies. We
      demonstrate that the distinct channel-resolved sequential and nonsequential ATDI
      spectra can clearly reveal the photon-induced acetylene-vinylidene isomerization
      via proton migration on the cation or dication states. 

PMID- 25955051
TI  - Decade-spanning high-precision terahertz frequency comb.
AB  - The generation and detection of a decade-spanning terahertz (THz) frequency comb
      is reported using two Ti:sapphire femtosecond laser oscillators and asynchronous
      optical sampling THz time-domain spectroscopy. The comb extends from 0.15 to 2.4
      THz, with a tooth spacing of 80 MHz, a linewidth of 3.7 kHz, and a fractional
      precision of 1.8*10^{-9}. With time-domain detection of the comb, we measure
      three transitions of water vapor at 10 mTorr between 1-2 THz with an average
      Doppler-limited fractional accuracy of 6.1*10^{-8}. Significant improvements in
      bandwidth, resolution, and sensitivity are possible with existing technologies.

PMID- 25955050
TI  - Conical dispersion and effective zero refractive index in photonic quasicrystals.
AB  - It is recognized that for a certain class of periodic photonic crystals, conical
      dispersion can be related to a zero-refractive index. It is not obvious whether
      such a notion can be extended to a noncrystalline system. We show that certain
      photonic quasicrystalline approximants have conical dispersions at the zone
      center with a triply degenerate state at the Dirac frequency, which is the
      necessary condition to qualify as a zero-refractive-index medium. The states in
      the conical dispersions are extended and have a nearly constant phase.
      Experimental characterizations of finite-sized samples show evidence that the
      photonic quasicrystals do behave as a near zero-refractive-index material around
      the Dirac frequency. 

PMID- 25955052
TI  - Excitation of magnetic dipole transitions at optical frequencies.
AB  - We use the magnetic field distribution of an azimuthally polarized focused laser
      beam to excite a magnetic dipole transition in Eu^{3+} ions embedded in a Y2O3
      nanoparticle. The absence of the electric field at the focus of an azimuthally
      polarized beam allows us to unambiguously demonstrate that the nanoparticle is
      excited by the magnetic dipole transition near 527.5 nm. When the laser
      wavelength is resonant with the magnetic dipole transition, the nanoparticle maps
      the local magnetic field distribution, whereas when the laser wavelength is
      resonant with an electric dipole transition, the nanoparticle is sensitive to the
      local electric field. Hence, by tuning the excitation wavelength, we can
      selectively excite magnetic or electric dipole transitions through optical
      fields.

PMID- 25955048
TI  - Single-Electron Detection and Spectroscopy via Relativistic Cyclotron Radiation.
AB  - It has been understood since 1897 that accelerating charges must emit
      electromagnetic radiation. Although first derived in 1904, cyclotron radiation
      from a single electron orbiting in a magnetic field has never been observed
      directly. We demonstrate single-electron detection in a novel radio-frequency
      spectrometer. The relativistic shift in the cyclotron frequency permits a precise
      electron energy measurement. Precise beta electron spectroscopy from gaseous
      radiation sources is a key technique in modern efforts to measure the neutrino
      mass via the tritium decay end point, and this work demonstrates a fundamentally
      new approach to precision beta spectroscopy for future neutrino mass experiments.

PMID- 25955054
TI  - Helium mass flow through a solid-superfluid-solid junction.
AB  - We report the results of flow experiments in which two chambers containing solid
      ^{4}He are connected by a superfluid Vycor channel. At low temperatures and
      pressures, mechanically squeezing the solid in one chamber produced a pressure
      increase in the second chamber, a measure of mass transport through our solid
      superfluid-solid junction. This pressure response is very similar to the flow
      seen in recent experiments at the University of Massachusetts: it began around
      600 mK, increased as the temperature was reduced, then decreased dramatically at
      a temperature, T_{d}, which depended on the ^{3}He impurity concentration. Our
      experiments indicate that the flow is limited by mass transfer across the solid
      liquid interface near the Vycor ends, where the ^{3}He collects at low
      temperature, rather than by flow paths within the solid ^{4}He. 

PMID- 25955055
TI  - Shear melting and high temperature embrittlement: theory and application to
      machining titanium.
AB  - We describe a dynamical phase transition occurring within a shear band at high
      temperature and under extremely high shear rates. With increasing temperature,
      dislocation deformation and grain boundary sliding are supplanted by
      amorphization in a highly localized nanoscale band, which allows for massive
      strain and fracture. The mechanism is similar to shear melting and leads to
      liquid metal embrittlement at high temperature. From simulation, we find that the
      necessary conditions are lack of dislocation slip systems, low thermal
      conduction, and temperature near the melting point. The first two are exhibited
      by bcc titanium alloys, and we show that the final one can be achieved
      experimentally by adding low-melting-point elements: specifically, we use
      insoluble rare earth metals (REMs). Under high shear, the REM becomes mixed with
      the titanium, lowering the melting point within the shear band and triggering the
      shear-melting transition. This in turn generates heat which remains localized in
      the shear band due to poor heat conduction. The material fractures along the
      shear band. We show how to utilize this transition in the creation of new
      titanium-based alloys with improved machinability. 

PMID- 25955057
TI  - Dynamics of water dissociative chemisorption on Ni(111): effects of impact sites
      and incident angles.
AB  - The dissociative chemisorption of water on rigid Ni(111) is investigated using a
      quasiclassical trajectory method on a nine-dimensional global potential energy
      surface based on a faithful permutation invariant fit of ~25 000 density
      functional theory points. This full-dimensional model not only confirms the
      validity of our earlier reduced-dimensional model with 6 degrees of freedom, but
      also allows the examination of the influence of impact sites and incident angles.
      It is shown that the reactivity depends on the site of impact in a complex
      fashion controlled by the topography of the potential energy surface rather than
      the barrier height alone. In addition, the reaction is promoted by momenta both
      parallel and perpendicular to the surface, as predicted by the recently proposed
      sudden vector projection model. 

PMID- 25955056
TI  - Bonding effects on the slip differences in the B1 monocarbides.
AB  - Differences in plasticity are usually attributed to significant changes in
      crystalline symmetry or the strength of the interatomic bonds. In the B1
      monocarbides, differences in slip planes exist at low temperatures despite having
      the same structure and very similar bonding characteristics. Our experimental
      results demonstrate concretely that HfC slips on {110} planes while TaC slips on
      {111} planes. Density functional theory calculations rationalize this difference
      through the formation of an intrinsic stacking fault on the {111} planes,
      formation of Shockley partials, and enhanced metallic bonding because of the
      valence filling of electrons between these transitional metal carbides. 

PMID- 25955053
TI  - Probing Atmospheric Electric Fields in Thunderstorms through Radio Emission from
      Cosmic-Ray-Induced Air Showers.
AB  - We present measurements of radio emission from cosmic ray air showers that took
      place during thunderstorms. The intensity and polarization patterns of these air
      showers are radically different from those measured during fair-weather
      conditions. With the use of a simple two-layer model for the atmospheric electric
      field, these patterns can be well reproduced by state-of-the-art simulation
      codes. This in turn provides a novel way to study atmospheric electric fields. 

PMID- 25955058
TI  - Atomic-Resolution STEM Imaging of Graphene at Low Voltage of 30 kV with
      Resolution Enhancement by Using Large Convergence Angle.
AB  - Atomic resolution at a low accelerating voltage with aberration correction is
      required to reduce the electron irradiation damage in scanning transmission
      electron microscopy imaging. However, the reduction in resolution caused by the
      diffraction limit becomes severe with increasing electron wavelength at low
      accelerating voltages. The developed aberration corrector can compensate for
      higher-order aberration in scanning transmission electron microscopy to expand
      the uniform phase angle. The resolution for imaging graphene at 30 kV is
      evaluated by changing the convergence angle for a probe-forming system with a
      higher-order aberration corrector. A single-carbon atom on graphene is
      successfully imaged at atomic resolution with a cold-field emission gun by dark
      field imaging at an accelerating voltage of 30 kV. 

PMID- 25955059
TI  - Critical Behavior of a Strongly Disordered 2D Electron System: The Cases of Long
      Range and Screened Coulomb Interactions.
AB  - A study of the temperature (T) and density (ns) dependence of conductivity
      sigma(ns,T) of a highly disordered, two-dimensional (2D) electron system in Si
      demonstrates scaling behavior consistent with the existence of a metal-insulator
      transition (MIT). The same critical exponents are found when the Coulomb
      interaction is screened by the metallic gate and when it is unscreened or long
      range. The results strongly suggest the existence of a disorder-dominated 2D MIT,
      which is not directly affected by the range of the Coulomb interactions.

PMID- 25955060
TI  - Novel P-T Phase Diagram of the Multiorbital Mott Insulator Sr2VO4.
AB  - The electrical and optical properties of the Mott insulator Sr2VO4 are
      investigated under high pressure on a phase pure polycrystalline sample. The
      system undergoes a pressure-driven insulator to metal transition (IMT) with a
      crossover between 20 and 24 GPa. The effect of pressure on the thermally driven
      electronic changes resulting from spin-orbital ordering transitions is studied. A
      multiorbital analysis of the low frequency optical conductivity spectra suggests
      a bandwidth-controlled and orbital selective nature of the Mott IMT transition.
      Dramatic enhancement of the low energy spectral weight in the high pressure
      correlated metallic phase is explained in terms of the formation of a
      quasiparticle peak in the spectral function of the narrow and degenerate d(yz,zx)
      orbitals. Our results overall establish a novel electronic phase diagram of
      tetragonal Sr2VO4.

PMID- 25955061
TI  - Site-selective mott transition in a quasi-one-dimensional vanadate V6O13.
AB  - The microscopic mechanism of the metal-insulator transition is studied by orbital
      resolved ^{51}V NMR spectroscopy in a prototype of the quasi-one-dimensional
      system V6O13. We uncover that the transition involves a site-selective d orbital
      order lifting twofold orbital degeneracy in one of the two VO6 chains. The other
      chain leaves paramagnetic moments on the singly occupied d(xy) orbital across the
      transition. The two chains respectively stabilize an orbital-assisted spin
      Peierls state and an antiferromagnetic long-range order in the ground state. The
      site-selective Mott transition may be a source of the anomalous metal and the
      Mott-Peierls duality.

PMID- 25955062
TI  - Topological Properties and the Dynamical Crossover from Mixed-Valence to Kondo
      Lattice Behavior in the Golden Phase of SmS.
AB  - We have investigated temperature-dependent behaviors of electronic structure and
      resistivity in a mixed-valent golden phase of SmS, based on the dynamical mean
      field-theory band-structure calculations. Upon cooling, the coherent Sm 4f bands
      are formed to produce the hybridization-induced pseudogap near the Fermi level,
      and accordingly the topology of the Fermi surface is changed to exhibit a
      Lifshitz-like transition. The surface states emerging in the bulk gap region are
      found to be not topologically protected states but just typical Rashba spin
      polarized states, indicating that SmS is not a topological Kondo semimetal. From
      the analysis of anomalous resistivity behavior in SmS, we have identified
      universal energy scales, which characterize the Kondo-mixed-valent semimetallic
      systems. 

PMID- 25955063
TI  - First-principles photoemission spectroscopy and orbital tomography in molecules
      from koopmans-compliant functionals.
AB  - The determination of spectral properties from first principles can provide
      powerful connections between microscopic theoretical predictions and experimental
      data, but requires complex electronic-structure formulations that fall outside
      the domain of applicability of common approaches, such as density-functional
      theory. We show here that Koopmans-compliant functionals, constructed to enforce
      piecewise linearity and the correct discontinuity derivative in energy
      functionals with respect to fractional occupation-i.e., with respect to charged
      excitations-provide molecular photoemission spectra and momentum maps of Dyson
      orbitals that are in excellent agreement with experimental ultraviolet
      photoemission spectroscopy and orbital tomography data. These results highlight
      the role of Koopmans-compliant functionals as accurate and inexpensive
      quasiparticle approximations to the spectral potential. 

PMID- 25955064
TI  - Signatures of majorana zero modes in spin-resolved current correlations.
AB  - We consider a normal lead coupled to a Majorana bound state. We show that the
      spin-resolved current correlations exhibit unique features which distinguish
      Majorana bound states from other low-energy resonances. In particular, the spin
      up and spin-down currents from a Majorana bound state are anticorrelated at low
      bias voltages, and become uncorrelated at higher voltages. This behavior is
      independent of the exact form of coupling to the lead, and of the direction of
      the spin polarization. In contrast, an ordinary low-energy Andreev bound state
      gives rise to a positive correlation between the spin-up and spin-down currents,
      and this spin-resolved current-current correlation approaches a nonzero constant
      at high bias voltages. We discuss experimental setups in which this effect can be
      measured. 

PMID- 25955065
TI  - Critical transport in weakly disordered semiconductors and semimetals.
AB  - Motivated by Weyl semimetals and weakly doped semiconductors, we study transport
      in a weakly disordered semiconductor with a power-law quasiparticle dispersion
      xi_{k}?k^{alpha}. We show, that in 2alpha dimensions short-correlated disorder
      experiences logarithmic renormalization from all energies in the band. We study
      the case of a general dimension d using a renormalization group, controlled by an
      epsilon=2alpha-d expansion. Above the critical dimensions, conduction exhibits a
      localization-delocalization phase transition or a sharp crossover (depending on
      the symmetries of the Hamiltonian) as a function of disorder strength. We utilize
      this analysis to compute the low-temperature conductivity in Weyl semimetals and
      weakly doped semiconductors near and below the critical disorder point. 

PMID- 25955066
TI  - Charge-to-Spin Conversion and Spin Diffusion in Bi/Ag Bilayers Observed by Spin
      Polarized Positron Beam.
AB  - Charge-to-spin conversion induced by the Rashba-Edelstein effect was directly
      observed for the first time in samples with no magnetic layer. A spin-polarized
      positron beam was used to probe the spin polarization of the outermost surface
      electrons of Bi/Ag/Al2O3 and Ag/Bi/Al2O3 when charge currents were only
      associated with the Ag layers. An opposite surface spin polarization was found
      between Bi/Ag/Al2O3 and Ag/Bi/Al2O3 samples with the application of a charge
      current in the same direction. The surface spin polarizations of both systems
      decreased exponentially with the outermost layer thickness, suggesting the
      occurrence of spin diffusion from the Bi/Ag interface to the outermost surfaces.
      This work provides a new technique to measure spin diffusion length.

PMID- 25955067
TI  - Spin-Flip and Element-Sensitive Electron Scattering in the BiAg2 Surface Alloy.
AB  - Heavy metal surface alloys represent model systems to study the correlation
      between electron scattering, spin-orbit interaction, and atomic structure. Here,
      we investigate the electron scattering from the atomic steps of monolayer
      BiAg_{2} on Ag(111) using quasiparticle interference measurements and density
      functional theory. We find that intraband transitions between states of opposite
      spin projection can occur via a spin-flip backward scattering mechanism driven by
      the spin-orbit interaction. The spin-flip scattering amplitude depends on the
      chemical composition of the steps, leading to total confinement for pure Bi step
      edges, and considerable leakage for mixed Bi-Ag step edges. Additionally, the
      different localization of the occupied and unoccupied surface bands at Ag and Bi
      sites leads to a spatial shift of the scattering potential barrier at pure Bi
      step edges. 

PMID- 25955068
TI  - Regular rather than chaotic origin of the resonant transport in superlattices.
AB  - We address the enhancement of electron transport in semiconductor superlattices
      that occurs in combined electric and magnetic fields when cyclotron rotation
      becomes resonant with Bloch oscillations. We show that the phenomenon is regular
      in origin, contrary to the widespread belief that it arises through chaotic
      diffusion. The theory verified by simulations provides an accurate description of
      earlier numerical results and suggests new ways of controlling resonant
      transport. 

PMID- 25955069
TI  - Effect of chiral symmetry on chaotic scattering from Majorana zero modes.
AB  - In many of the experimental systems that may host Majorana zero modes, a so
      called chiral symmetry exists that protects overlapping zero modes from splitting
      up. This symmetry is operative in a superconducting nanowire that is narrower
      than the spin-orbit scattering length, and at the Dirac point of a superconductor
      topological insulator heterostructure. Here we show that chiral symmetry strongly
      modifies the dynamical and spectral properties of a chaotic scatterer, even if it
      binds only a single zero mode. These properties are quantified by the Wigner
      Smith time-delay matrix Q=-ihS^{?}dS/dE, the Hermitian energy derivative of the
      scattering matrix, related to the density of states by rho=(2pih)^{-1}TrQ. We
      compute the probability distribution of Q and rho, dependent on the number nu of
      Majorana zero modes, in the chiral ensembles of random-matrix theory. Chiral
      symmetry is essential for a significant nu dependence. 

PMID- 25955070
TI  - Spin-orbit interactions and the nematicity observed in the fe-based
      superconductors.
AB  - High-resolution angle-resolved photoelectron spectroscopy is used to examine the
      electronic band structure of FeTe_{0.5}Se_{0.5} near the Brillouin zone center. A
      consistent separation of the alpha_{1} and alpha_{2} bands is observed with
      little k_{z} dependence of the alpha_{1} band. First-principles calculations for
      bulk and thin films demonstrate that the antiferromagnetic coupling between the
      Fe atoms and hybridization-induced spin-orbit effects lifts the degeneracy of the
      Fe d_{xz} and d_{yz} orbitals at the zone center leading to orbital ordering.
      These experimental and computational results provide a natural microscopic basis
      for the nematicity observed in the Fe-based superconductors. 

PMID- 25955071
TI  - Long-range spin accumulation from heat injection in mesoscopic superconductors
      with Zeeman splitting.
AB  - We describe far-from-equilibrium nonlocal transport in a diffusive
      superconducting wire with a Zeeman splitting, taking into account different spin
      relaxation mechanisms. We demonstrate that due to the Zeeman splitting, an
      injection of current in a superconducting wire creates spin accumulation that can
      only relax via thermalization. This effect leads to a long-range spin
      accumulation detectable in the nonlocal signal. Our model gives a qualitative
      explanation and provides accurate fits of recent experimental results in terms of
      realistic parameters. 

PMID- 25955072
TI  - Quantum Paramagnet in a pi Flux Triangular Lattice Hubbard Model.
AB  - We propose the pi flux triangular lattice Hubbard model (pi THM) as a
      prototypical setup to stabilize magnetically disordered quantum states of matter
      in the presence of charge fluctuations. The quantum paramagnetic domain of the pi
      THM that we identify for intermediate Hubbard U is framed by a Dirac semimetal
      for weak coupling and by 120 degrees  Neel order for strong coupling.
      Generalizing the Klein duality from spin Hamiltonians to tight-binding models,
      the pi THM maps to a Hubbard model which corresponds to the (J_{H},J_{K})=(-1,2)
      Heisenberg-Kitaev model in its strong coupling limit. The pi THM provides a
      promising microscopic testing ground for exotic finite-U spin liquid ground
      states amenable to numerical investigation. 

PMID- 25955073
TI  - Collective motion of self-propelled particles with memory.
AB  - We show that memory, in the form of underdamped angular dynamics, is a crucial
      ingredient for the collective properties of self-propelled particles. Using
      Vicsek-style models with an Ornstein-Uhlenbeck process acting on angular
      velocity, we uncover a rich variety of collective phases not observed in usual
      overdamped systems, including vortex lattices and active foams. In a model with
      strictly nematic interactions the smectic arrangement of Vicsek waves giving rise
      to global polar order is observed. We also provide a calculation of the effective
      interaction between vortices in the case where a telegraphic noise process is at
      play, explaining thus the emergence and structure of the vortex lattices observed
      here and in motility assay experiments. 

PMID- 25955074
TI  - Synaptic democracy and vesicular transport in axons.
AB  - Synaptic democracy concerns the general problem of how regions of an axon or
      dendrite far from the cell body (soma) of a neuron can play an effective role in
      neuronal function. For example, stimulated synapses far from the soma are
      unlikely to influence the firing of a neuron unless some sort of active dendritic
      processing occurs. Analogously, the motor-driven transport of newly synthesized
      proteins from the soma to presynaptic targets along the axon tends to favor the
      delivery of resources to proximal synapses. Both of these phenomena reflect
      fundamental limitations of transport processes based on a localized source. In
      this Letter, we show that a more democratic distribution of proteins along an
      axon can be achieved by making the transport process less efficient. This
      involves two components: bidirectional or "stop-and-go" motor transport (which
      can be modeled in terms of advection-diffusion), and reversible interactions
      between motor-cargo complexes and synaptic targets. Both of these features have
      recently been observed experimentally. Our model suggests that, just as in human
      societies, there needs to be a balance between "efficiency" and "equality". 

PMID- 25955075
TI  - Public good diffusion limits microbial mutualism.
AB  - Standard game theory cannot describe microbial interactions mediated by
      diffusible molecules. Nevertheless, we show that one can still model microbial
      dynamics using game theory with parameters renormalized by diffusion. Contrary to
      expectations, greater sharing of metabolites reduces the strength of cooperation
      and leads to species extinction via a nonequilibrium phase transition. We report
      analytic results for the critical diffusivity and the length scale of species
      intermixing. Species producing slower public good is favored by selection when
      fitness saturates with nutrient concentration. 

PMID- 25955076
TI  - Shear-driven failure of liquid-infused surfaces.
AB  - Rough or patterned surfaces infused with a lubricating liquid display many of the
      same useful properties as conventional gas-cushioned superhydrophobic surfaces.
      However, liquid-infused surfaces exhibit a new failure mode: the infused liquid
      film may drain due to an external shear flow, causing the surface to lose its
      advantageous properties. We examine shear-driven drainage of liquid-infused
      surfaces with the goal of understanding and thereby mitigating this failure mode.
      On patterned surfaces exposed to a known shear stress, we find that a finite
      length of the surface remains wetted indefinitely, despite the fact that no
      physical barriers prevent drainage. We develop an analytical model to explain our
      experimental results, and find that the steady-state retention results from the
      ability of patterned surfaces to wick wetting liquids, and is thus analogous to
      capillary rise. We establish the geometric surface parameters governing fluid
      retention and show how these parameters can describe even random substrate
      patterns. 

PMID- 25955077
TI  - Comment on "measurement of two- and three-nucleon short-range correlation
      probabilities in nuclei".

PMID- 25955078
TI  - Cryo-electron microscopy and the amazing race to atomic resolution.
AB  - Cryo-electron microscopy (cryo-EM), the structural analysis of samples embedded
      in vitreous ice, is a powerful approach for determining three-dimensional (3D)
      structures of biological specimens. Over the past two decades, this technique has
      been used to successfully calculate subnanometer (<10 A) resolution and, in some
      cases, near-atomic resolution structures of highly symmetrical and stable
      complexes such as icosahedral viruses and ribosomes, as well as samples that form
      ordered two-dimensional or helical arrays. However, determining high-resolution
      3D structures of smaller, less symmetrical, and dynamic samples remains a
      significant challenge. The recent development of electron microscopes with
      automated data collection capabilities and robust direct electron detection
      cameras, as well as new powerful image processing algorithms, has dramatically
      expanded the number of biological macromolecules amenable for study using cryo
      EM. In addition, these new technological and computational developments have been
      used to successfully determine <5 A resolution 3D structures of samples, such as
      membrane proteins and complexes with either low or no symmetry, that
      traditionally were not considered promising candidates for high-resolution cryo
      EM. With these exciting new advances, cryo-EM is now on pace to determine atomic
      resolution 3D structures. 

PMID- 25955079
TI  - Safety and efficacy of pharmacological thromboprophylaxis for hospitalized
      patients with cirrhosis: a single-center retrospective cohort study.
AB  - BACKGROUND: Hospitalized patients with cirrhosis are at increased risk for venous
      thromboembolism (VTE). The benefits and risks of pharmacological
      thromboprohylaxis in these patients have not been well studied. OBJECTIVES: To
      examine the safety and efficacy of pharmacological VTE prophylaxis in
      hospitalized cirrhotic patients. PATIENTS/METHODS: Retrospective cohort study of
      patients with cirrhosis hospitalized at an academic tertiary care referral center
      over a 5-year period. RESULTS: Six hundred hospital admissions accounting for 402
      patients were included. VTE prophylaxis was administered during 296 (49%)
      admissions. Patients receiving VTE prophylaxis were older (59 years vs. 55 years,
      P < 0.001), had longer lengths of stay (9.6 days vs. 6.8 days, P = 0.002), and
      lower Model for End-Stage Liver Disease scores (13.2 vs. 16.1, P < 0.001). In
      hospital bleeding events (8.1% vs. 5.5%, P = 0.258), gastrointestinal bleeding
      events (3.0% vs. 3.2% P = 0.52), new VTE events (2.37% vs. 1.65%, P = 0.537), and
      mortality (8.4% vs. 7.3%, P = 0.599) were similar in the two groups. VTE
      prophylaxis did not reduce the risk of VTE (odds ratio 0.94, 95% confidence
      interval 0.23-3.71), and patients receiving unfractionated heparin, but not low
      molecular weight heparin, were at increased risk for in-hospital bleeding events
      (odds ratio 2.38, 95% confidence interval 1.15-4.94 vs. 0.87, 0.37-2.05,
      respectively). CONCLUSION: The rate of VTE in this cohort of hospitalized
      cirrhotic patients was low and was unaffected by pharmacological
      thromboprophylaxis. Unfractionated heparin was associated with an increased risk
      for in-hospital bleeding, suggesting that if thromboprophylaxis is indicated, low
      molecular weight heparin may be favored.

PMID- 25955080
TI  - Birth Characteristics and Childhood Leukemia Risk: Correlations With Genetic
      Markers.
AB  - Birth characteristics such as birth order, birth weight, birth defects, and Down
      syndrome showed some of the first risk associations with childhood leukemia.
      Examinations of correlations between birth characteristics and leukemia risk
      markers have been limited to birth weight-related genetic polymorphisms. We
      integrated information on nongenetic and genetic markers by evaluating the
      relationship of birth characteristics, genetic markers for childhood acute
      lymphoblastic leukemia (ALL) susceptibility, and ALL risk together. The
      multiethnic study consisted of cases with childhood ALL (n=161) and healthy
      controls (n=261). Birth characteristic data were collected through
      questionnaires, and genotyping was achieved by TaqMan SNP Genotyping Assays. We
      observed risk associations for birth weight over 4000 g (odds ratios [OR]=1.93;
      95% confidence interval [CI], 1.16-3.19), birth length (OR=1.18 per inch; 95% CI,
      1.01-1.38), and with gestational age (OR=1.10 per week; 95% CI, 1.00-1.21). Only
      the HFE tag single-nucleotide polymorphism (SNP) rs9366637 showed an inverse
      correlation with a birth characteristic, gestational age, with a gene-dosage
      effect (P=0.005), and in interaction with a transferrin receptor rs3817672
      genotype (Pinteraction=0.05). This correlation translated into a strong
      association for rs9366637 with preterm birth (OR=5.0; 95% CI, 1.19-20.9). Our
      study provides evidence for the involvement of prenatal events in the development
      of childhood ALL. The inverse correlation of rs9366637 with gestational age has
      implications on the design of HFE association studies in birth weight and
      childhood conditions using full-term newborns as controls. 

PMID- 25955081
TI  - Why do we need systematic reviews to inform healthcare decisions in the disaster
      context.
AB  - Decision-making in the disaster setting is often guided by the precautionary
      principle and the pressure to do something. All such actions do not necessarily
      translate into improved outcomes, however well-reasoned and well-intentioned they
      might be. Systematic reviews of interventions could provide the credible evidence
      needed to inform decision-making in the disaster context. In this paper, which
      was presented at the Evidence Aid Symposium on 20 September 2014, at Hyderabad,
      India, I emphasize this point by reflecting upon the response to the recent
      pandemic (H1N1) 2009 influenza. 

PMID- 25955082
TI  - Novel mutations associated with a discrepancy between one-stage and chromogenic
      FVIII activity assays.

PMID- 25955083
TI  - Comparison of the proliferation, cytotoxic activity and cytokine secretion
      function of cascade primed immune cells and cytokine-induced killer cells in
      vitro.
AB  - The present study aimed to compare the antitumor effects of cascade primed immune
      (CAPRI) cells and cytokine-induced killer (CIK) cells in vitro, through
      investigating cell morphology, proliferation, cytotoxic activity to tumor cells
      and the ability of these cells to secrete cytokines. Peripheral blood samples (50
      ml) were obtained from three healthy volunteers and peripheral blood mononuclear
      cells (PBMCs) were obtained from each via Ficoll-Conray density gradient
      centrifugation. Each suspension of PBMCs (1 x 10(6)/ml) was divided into two
      parts; CAPRI cells were obtained from one part through a series of induction,
      amplification and cytokine cultures, while CIK cells were obtained from the other
      part through induction with different cytokines. During the culture process, the
      proliferation and morphological changes were observed for the two cell types
      using Trypan blue staining. At day 14, the cytotoxic activity of the two cell
      types was examined through determining lactate dehydrogenase release in the
      presence of K562 leukemia cells and MCF-7 breast cancer cells. In addition,
      secretory levels of interferon (IFN)-gamma and interleukin (IL)-2 were detected
      using enzyme-linked immunospot (ELISPOT) technology. The results revealed that at
      day 5 and 14 of culture, there were significantly fewer CAPRI cells compared with
      CIK cells (P<0.001), although the survival rate of each cell type was >95%. The
      cytotoxic activity of CAPRI cells towards the K562 cell line was effector-target
      ratio-dependent (40:1 and 20:1) with values of 55.1 +/- 3.25 and 35.0 +/- 2.65%,
      respectively, which were significantly reduced compared with the corresponding
      data in CIK cells, 60.0 +/- 3.03 and 39.7 +/- 3.42% (P=0.004 and 0.005,
      respectively). Furthermore, the cytotoxic activity of CAPRI cells towards MCF-7
      cells were 71.5 +/- 3.06, 56.0 +/- 3.76 and 40.2 +/- 2.90% at effector-target
      ratios 40:1, 20:1 and 10:1, respectively. These data were significantly higher
      than the corresponding values in CIK cells, 65.4 +/- 3.86, 49.5 +/- 3.91 and 36.1
      +/- 3.73% (P=0.002, 0.003 and 0.02, respectively). As determined using ELISPOT
      technology at different cell concentrations (1 x 10(6)/ml and 5 x 10(5)/ml), IFN
      gamma secretion levels, determined by the number of spot-forming cells, of CAPRI
      cells were 126.2 +/- 10.31 and 48.8 +/- 10.99, respectively, which were
      significantly reduced compared with those of CIK cells, 409.3 +/- 7.76 and 159.3
      +/- 15.45, respectively (P<0.001). IL-2 secretion levels in CAPRI cells were
      325.1 +/- 16.24 and 113.8 +/- 11.29 at 1 x 10(6)/ml and 5 x 10(5)/ml,
      respectively, which were significantly increased compared with CIK cells, 212.0
      +/- 16.58 and 70.7 +/- 10.57, respectively (P<0.001). In conclusion, the present
      study demonstrated that CAPRI cells had a reduced proliferation rate compared
      with CIK cells as well as a less potent cytotoxic effect on K562 cells; however,
      the two cell types had potent cytotoxic activity towards solid tumor MCF-7 cells.
      In addition, CAPRI cells secreted lower levels of IFN-gamma and increased levels
      of IL-2 compared with CIK cells. These results indicated that antitumor
      activities of CAPRI and CIK cells proceeded via different mechanisms.

PMID- 25955084
TI  - Glycosyltransferases as marker genes for the quantitative polymerase chain
      reaction-based detection of circulating tumour cells from blood samples of
      patients with breast cancer undergoing adjuvant therapy.
AB  - Altered glycosylation is a predominant feature of tumour cells; it serves for
      cell adhesion and detachment, respectively, and facilitates the immune escape of
      these cells. Therefore changes in the expression of glycosyltransferase genes
      could help to identify circulating tumour cells (CTCs) in the blood samples of
      cancer patients using a quantitative polymerase chain reaction (PCR) approach.
      Blood samples of healthy donors were inoculated with certain numbers of
      established breast cancer cell line cells, thus creating a model system. These
      samples were analysed by quantitative PCR for the expression of six different
      glycosyltransferase genes. The three genes with the best results in the model
      system were consecutively applied to samples from adjuvant breast cancer patients
      and of healthy donors. FUT3 and GALNT6 showed the highest increase in relative
      expression, while GALNT6 and ST3GAL3 were the first to reach statistically
      significant different ?CT-values comparing the sample with and without addition
      of tumour cells. These three genes were applied to patient samples, but did not
      show any significant results that may suggest the presence of CTCs in the blood.
      Although the relative expression of some of the glycosyltransferase genes
      exhibited reasonable results in the model system, their application to breast
      cancer patient samples will have to be further improved, e.g. by co-analysis of
      patient blood samples by gold-standard methods.

PMID- 25955085
TI  - Transcription factor regulatory network for early lung immune response to
      tuberculosis in mice.
AB  - Numerous transcription factors (TFs) have been suggested to have a role in
      Mycobacterium tuberculosis infection; however, the TFs involved in the early
      immune response of lung cells remains to be fully elucidated. The present study
      aimed to identify TFs which may have a role in the early immune response to
      tuberculosis and the gene regulatory networks in which they are involved. Gene
      expression data obtained from microarray analysis of the early lung immune
      response to tuberculosis (Gene Expression Omnibus; accession no. GSE23014) was
      integrated with data for TF binding sites and protein-protein interactions in
      order to construct a TF regulatory network. The role of TFs in protein complexes,
      active modules, topology of the network and regulation of immune processes were
      investigated. The results demonstrated that the constructed gene regulatory
      network harbored 1,270 differentially expressed (DE) genes with 4,070 regulatory
      and protein-protein interactions. In addition, it was revealed that 17 DE TFs
      were involved in the positive regulation of numerous immunological and biological
      processes, including T cell activation, T cell proliferation and tuberculosis
      associated gene expression, in the constructed regulatory network. Signal
      transducer and activator of transcription 4, interferon regulatory factor 8,
      spleen focus-forming virus proviral integration 1, enhancer of zeste homolog 2
      and kruppel-like factor 4 were predicted to be the primary TFs regulating the DE
      genes during early lung infection by M. tuberculosis, as determined through
      various analyses of the gene regulatory network. In conclusion, the present study
      identified novel TFs involved in the early response to M. tuberculosis infection,
      which may enhance current understanding of the molecular mechanism underlying
      tuberculosis infection and introduced potential targets for novel tuberculosis
      therapies.

PMID- 25955086
TI  - Long-term Outcomes of the US FDA IDE Prospective, Randomized Controlled Clinical
      Trial Comparing PCM Cervical Disc Arthroplasty With Anterior Cervical Discectomy
      and Fusion.
AB  - STUDY DESIGN: Prospective, multicenter, randomized clinical trial. OBJECTIVE: To
      evaluate the long-term safety and effectiveness of the PCM Cervical Disc compared
      with anterior cervical discectomy and fusion (ACDF) in treatment of patients with
      symptomatic single-level degenerative spondylosis between C3-C4 and C7-T1 with or
      without prior cervical fusion. SUMMARY OF BACKGROUND DATA: The 2-year results of
      the PCM Cervical Disc trial have been reported previously. The current study
      reports the long-term results of the same trial. METHODS: Patients with single
      level cervical spondylosis and radiculopathy with or without myelopathy
      unresponsive to nonoperative treatment were enrolled. The per protocol patient
      sample at 5 years included 293 patients (163 PCM, 130 ACDF). Adverse events and
      secondary surgical procedures are reported on the cohorts through current follow
      up, which include 110 patients (68 PCM, 42 ACDF) at 7 years. RESULTS: At 5 years
      postoperative, all patient-reported outcomes-neck and arm pain visual analogue
      scale score, neck disability index, and general health (36-Item Short Form Health
      Survey physical and mental component scores: physical component summary, mental
      component summary)-were significantly improved from baselines in both groups, and
      mean scores were significantly better in the PCM group for neck disability index
      (P=0.001), neck pain (P=0.002), general health (Pphysical component
      summary=0.014; Pmental component summary=0.004), and patient satisfaction
      (P=0.005). PCM patients trended toward fewer 2- to 7-year device-related serious
      adverse events (1/214, 0.5% PCM; 2/190, 1.1% ACDF) and secondary surgical
      procedures (7/211, 3.3% PCM; 14/290, 7.6% ACDF). Adjacent-level degeneration was
      radiographically more frequent after ACDF (33.1% PCM, 50.9% ACDF; P=0.006) and
      was the primary indication for the increase in late-term secondary surgical
      procedures after ACDF. CONCLUSION: The long-term results show good clinical
      outcomes after ACDF and PCM arthroplasty. PCM patients showed greater improvement
      in neck disability index and neck pain scores with a lower rate of radiographical
      adjacent-level degeneration and a trend toward fewer secondary surgical
      procedures. These data support PCM arthroplasty to be a viable and sustainable
      alternative to ACDF. LEVEL OF EVIDENCE: 1.

PMID- 25955087
TI  - Anatomic study and clinical significance of the dorsal meningovertebral ligaments
      of the thoracic dura mater.
AB  - STUDY DESIGN: A dissection-based study of 18 embalmed thoracic specimens.
      OBJECTIVE: To investigate the properties and clinical significance of the dorsal
      meningovertebral ligaments of the thoracic dura mater. SUMMARY OF BACKGROUND
      DATA: Previously, we performed a comprehensive anatomic study on the dorsal
      meningovertebral ligaments in the lumbosacral and cervical regions, whereby we
      concluded that the ligaments were an anatomic factor leading to dural laceration
      and hemorrhage during flavectomy and laminectomy. Unfortunately, thus far, no
      systematic anatomic study has been undertaken to examine the dorsal
      meningovertebral ligaments of the thoracic dura mater. METHODS: Eighteen adult
      embalmed cadavers were studied, and the morphology, orientation, attachment site,
      and distribution traits of the dorsal meningovertebal ligaments were observed. In
      addition, the length, width, or diameter and thickness of the ligaments were
      measured using a Vernier caliper. Two meningovertebal ligaments were removed for
      histological examination. RESULTS: In the thoracic region, the dorsal
      meningovertebral ligaments anchored the dura mater to the lamina or ligamentum
      flavum. The meningovertebral ligaments displayed a relatively even distribution
      along the upper thoracic region (T1-T7) and a gradual increase in frequency in
      the lower thoracic region from T7 to T12. The meningovertebral ligaments protrude
      into the dura and correspondingly become an integral part of the dura. Some
      ligaments are accompanied by or are attached to blood vessels. Histological
      examination of the meningovertebral ligaments revealed fibrous connective tissue.
      CONCLUSION: The dorsal meningovertebral ligaments exist between the dural sac and
      ligamentum flavum or lamina in the thoracic spine. Based on their anatomic
      features, meningovertebral ligaments may be one potential cause for dural
      laceration and epidural hemorrhage. We propose that, during thoracic flavectomy
      and laminectomy, the meningovertebral ligaments should first be identified and
      properly handled, thereby minimizing the occurrence of relevant complications.
      LEVEL OF EVIDENCE: N/A.

PMID- 25955088
TI  - Could less be more when assessing patient-rated outcome in spinal stenosis?
AB  - STUDY DESIGN: Longitudinal study of the measurement properties of a brief outcome
      instrument. OBJECTIVE: In patients undergoing surgery for lumbar spinal stenosis,
      we compared the responsiveness of the Core Outcome Measures Index (COMI) with
      that of the condition-specific Swiss Spinal Stenosis Measure (SSM), an instrument
      developed to assess patients with neurogenic claudication. SUMMARY OF BACKGROUND
      DATA: The COMI is a validated multidimensional questionnaire for assessing the
      key outcomes of importance to patients with back problems. Being brief, it is
      associated with minimal respondent burden and high completion rates. However, for
      a given pathology, intuitively it may be expected to be less responsive than a
      condition-specific instrument. METHODS: A total of 91 patients (73+/-8 yr; 53%
      males) completed the following questionnaires before surgery: COMI, SSM, Roland
      Morris Disability Questionnaire, back trouble "Feeling Thermometer," pain numeric
      rating scale, EuroQoL-visual analogue scale. Twelve months postoperatively, 78/91
      (86%) completed all the questionnaires again; they also rated the "global
      treatment outcome" (GTO; rated 1-5) and SSM "satisfaction with treatment result"
      (SSM-sat; rated 1-4), which were used as external criteria of treatment success.
      RESULTS: Scores for the external criteria of success (GTO/SSM-sat) correlated
      with the change scores (baseline to 12 mo) in COMI (r=0.57) and SSM (r=0.54) to a
      similar extent. Using receiver operating characteristics, with GTO or SSM-sat
      dichotomized as external criterion, the area under the curve was similar for the
      COMI change score (0.86-0.90) and the SSM (sub)scales (0.80-0.90). CONCLUSION:
      With either SSM-sat or GTO serving as the external criterion, COMI was as
      responsive as the SSM. The COMI is well able to detect important change in lumbar
      spinal stenosis and has the added benefit of reducing the response burden for the
      patient and facilitating outcome comparisons with other spinal pathologies. LEVEL
      OF EVIDENCE: 2.

PMID- 25955089
TI  - Ventral epidural filling technique in interlaminar epidural steroid injection.
AB  - STUDY DESIGN: A retrospective case-control study. OBJECTIVE: To evaluate the
      safety and efficacy of the ventral epidural filling technique in lumbar
      interlaminar epidural steroid injection (ESI). SUMMARY OF BACKGROUND DATA: The
      ventral epidural space can be a preferred target in ESI because it contains many
      spinal pain generators. However, there have been few studies regarding the
      ventral epidural space filling technique in interlaminar ESI. METHODS: This study
      involved a retrospective analysis of 150 consecutive patients treated with the
      ventral epidural filling technique in interlaminar ESI (ventral ESI) and a
      control cohort of 150 consecutive patients treated with the dorsal epidural
      filling technique in interlaminar ESI (conventional ESI). The visual analogue
      scale for leg pain, the visual analogue scale for back pain, and the Oswestry
      Disability Index were compared at preinjection and 2 weeks, 6 weeks, 6 months,
      and 1 year postinjection. The groups were compared with regard to repeated
      injection or surgery within 1 year after the initial procedure. The fluoroscopic
      time and the procedure-related complications including severe pain (visual
      analogue scale score>7) during injection, dural puncture (subdural contrast
      spread), headache, neurological symptoms, and infection were also compared.
      RESULTS: There were no significant differences in leg pain, back pain, or
      Oswestry Disability Index improvement at each visit between the ventral ESI group
      and the conventional ESI group (all P>0.05). The numbers of repeat injections and
      surgical procedures were not significantly different between 2 groups (P=0.262
      and 0.385, respectively). There were no significant differences in severe pain at
      injection (P=0.326), dural puncture (P=0.428), headache (P=0.393), neurological
      symptom (P=0.419), or infection (P=0.500) between the 2 groups. The fluoroscopic
      time was significantly shorter in ventral than in conventional ESI (P<0.000).
      CONCLUSION: The ventral epidural filling technique can be performed safely and
      more easily during lumbar interlaminar ESI. The clinical results and procedure
      related complications with this technique were comparable with those seen with
      conventional interlaminar ESI. LEVEL OF EVIDENCE: 3.

PMID- 25955090
TI  - Can we convert between outcome measures of disability for chronic low back pain?
AB  - STUDY DESIGN: Retrospective database analysis. OBJECTIVE: A range of patient
      reported outcomes were used to measure disability due to low back pain. There is
      not a single back pain disability measurement commonly used in all randomized
      controlled trials. We report here our assessment as to whether different
      disability measures are sufficiently comparable to allow data pooling across
      trials. SUMMARY OF BACKGROUND DATA: We used individual patient data from a
      repository of data from back pain trials of therapist-delivered interventions.
      METHODS: We used data from 11 trials (n=6089 patients) that had at least 2 of the
      following 7 measurements: Roland-Morris Disability Questionnaire, Chronic Pain
      Grade disability score, Physical Component Summary of the 12- or 36-Item Short
      Form Health Survey, Patient Specific Functional Scale, Pain Disability Index,
      Oswestry Disability Index, and Hannover Functional Ability Questionnaire. Within
      each trial, the change score between baseline and short-term follow-up was
      computed for each outcome and this was used to calculate the correlation between
      the change scores and the Cohen's kappa for the 3-level outcome of change score
      of less than, equal to, and more than zero. It was considered feasible to pool 2
      measures if they were at least moderately correlated (correlation>0.5) and have
      at least moderately similar responsiveness (kappa>0.4). RESULTS: Although all
      pairs of measures were found to be positively correlated, most correlations were
      less than 0.5, with only 1 pair of outcomes in 1 trial having a correlation of
      more than 0.6. All kappa statistics were less than 0.4 so that in no cases were
      the criteria for acceptability of pooling measures satisfied. CONCLUSION: The
      lack of agreement between different outcome measures means that pooling of data
      on these different disability measurements in a meta-analysis is not recommended.
      LEVEL OF EVIDENCE: 2.

PMID- 25955091
TI  - The top 100 classic papers in lumbar spine surgery.
AB  - STUDY DESIGN: Bibliometric review of the literature. OBJECTIVE: To analyze and
      quantify the most frequently cited papers in lumbar spine surgery and to measure
      their impact on the entire lumbar spine literature. SUMMARY OF BACKGROUND DATA:
      Lumbar spine surgery is a dynamic and complex field. Basic science and clinical
      research remain paramount in understanding and advancing the field. While new
      literature is published at increasing rates, few studies make long-lasting
      impacts. METHODS: The Thomson Reuters Web of Knowledge was searched for citations
      of all papers relevant to lumbar spine surgery. The number of citations,
      authorship, year of publication, journal of publication, country of publication,
      and institution were recorded for each paper. RESULTS: The most cited paper was
      found to be the classic paper from 1990 by Boden et al that described magnetic
      resonance imaging findings in individuals without back pain, sciatica, and
      neurogenic claudication showing that spinal stenosis and herniated discs can be
      incidentally found when scanning patients. The second most cited study similarly
      showed that asymptomatic patients who underwent lumbar spine magnetic resonance
      imaging frequently had lumbar pathology. The third most cited paper was the 2000
      publication of Fairbank and Pynsent reviewing the Oswestry Disability Index, the
      outcome-measure questionnaire most commonly used to evaluate low back pain. The
      majority of the papers originate in the United States (n=58), and most were
      published in Spine (n=63). Most papers were published in the 1990s (n=49), and
      the 3 most common topics were low back pain, biomechanics, and disc degeneration.
      CONCLUSION: This report identifies the top 100 papers in lumbar spine surgery and
      acknowledges those individuals who have contributed the most to the advancement
      of the study of the lumbar spine and the body of knowledge used to guide evidence
      based clinical decision making in lumbar spine surgery today. LEVEL OF EVIDENCE:
      3.

PMID- 25955092
TI  - Clinical depression is a strong predictor of poor lumbar fusion outcomes among
      workers' compensation subjects.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Determine how psychosocial
      factors, particularly depression, impact lumbar fusion outcomes in a workers'
      compensation (WC) setting. SUMMARY OF BACKGROUND DATA: WC patients are less
      likely to return to work (RTW) after fusion. Few studies evaluate risk factors
      within this clinically distinct population. METHODS: A total of 2799 Ohio WC
      subjects were identified who underwent lumbar fusion between 1993 and 2013 using
      Current Procedural Terminology (CPT) procedural and International Classification
      of Diseases, Ninth Revision (ICD-9) diagnosis codes. A total of 123 subjects were
      diagnosed with depression before fusion. Subjects with a smoking history, prior
      lumbar surgery, permanent disability, and failed back syndrome were excluded. The
      primary outcome was whether subjects returned to work within 2 years of fusion
      and sustained this RTW for more than 6 months of the following year. To determine
      the impact depression had on RTW status, we performed a multivariate logistic
      regression analysis. We also compared time absent from work and other secondary
      outcomes using chi2 and t tests. RESULTS: Subjects with preoperative depression
      had significantly higher rates of legal representation, degenerative lumbar
      disease, and higher medical costs, and used opioid analgesics for considerably
      longer before and after fusion (P<0.001).Depression group (10.6% [13/123]) and
      controls (33.0% [884/2676]) met our RTW criteria (P<0.001). Preoperative
      depression was a negative predictor of RTW status (P<0.001; odds ratio [OR]:
      0.38). Additional predictors included working during same week as fusion (OR:
      2.15), age more than 50 years (OR: 0.58), chronic preoperative opioid analgesia
      (OR: 0.58), and legal representation (OR: 0.64). After surgery, depression
      subjects were absent from work 184 more days compared with controls (P<0.001).
      CONCLUSION: Overall, RTW rates after fusion were low, which was especially true
      for those with pre-existing depression. Depression was a strong negative
      predictor of postoperative RTW status. Psychological screening and treatment may
      be beneficial in these subjects. The poor outcomes in this study may highlight a
      more limited role for fusion among WC subjects with chronic low back pain where
      RTW is the treatment goal. LEVEL OF EVIDENCE: 3.

PMID- 25955093
TI  - Does a zero-profile anchored cage offer additional stabilization as anterior
      cervical plate?
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: This study aimed to compare
      3 different surgical methods of single-level anterior cervical interbody fusion
      consisting of stand-alone cages (SCs), cages with plates (CPs), and anchored
      cages (ACs) (zero-profile). It focused on postoperative retention and motion
      stabilization. SUMMARY OF BACKGROUND DATA: Several authors reported the
      radiological and clinical results of ACs, which seem similar to plates. However,
      it remains unclear whether ACs offer additional stabilization like plates.
      METHODS: Between 2005 and 2011, SCs (n=60) and CPs (n=18) were used to surgically
      treat patients with single-level cervical degenerative diseases. From January
      2012 to June 2013, ACs were used (n=23). We compared retention (cervical
      alignment, segmental angle, and segmental height) and motion stabilization
      (change of segmental angle and distance of interspinous process in
      flexion/extension). We also investigated subsidence, fusion rates, and clinical
      outcomes. The mean follow-up period was 19.9 months. RESULTS: The CP and AC
      groups showed significantly more retention at 12 months after surgery than the SC
      group (P<0.05). The CP group had significantly greater motion stabilization than
      the SC group (P<0.05). However, there was no statistically significant difference
      between the AC and SC groups. The subsidence rates of the SC, AC, and CP groups
      were 40.0%, 21.7%, and 11.1%, whereas the fusion rates were 83.3%, 87.0%, and
      100.0%, respectively. Arm and neck visual analogue scale scores and Odom criteria
      showed superior results in the CP and AC groups than in the SC group (P<0.05).
      CONCLUSION: The AC displayed similar retention and clinical outcomes to those of
      the CP. However, the AC was inferior to the CP in motion stabilization,
      subsidence prevention, and fusion rate. Therefore, for patients who require
      strong postoperative motion stabilization, CPs rather than ACs should be used.
      LEVEL OF EVIDENCE: 4.

PMID- 25955094
TI  - Can bacterial infection by low virulent organisms be a plausible cause for
      symptomatic disc degeneration? A systematic review.
AB  - STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To review and
      assess the current evidence from the literature on the potential association
      between disc infection with the development of symptomatic degenerative disc
      disease. SUMMARY OF BACKGROUND DATA: The potential relationship between disc
      infection- and disc degeneration-related symptoms remains controversial, with
      contradictory evidence available in the literature. Several studies have
      demonstrated the presence of infected extruded nucleus tissue from first-time
      disc herniations, implicating the role of disc microbial infection as a pathway
      for disc degeneration. In contrast, other studies reported very low prevalence of
      bacterial infection in samples from patients with sciatica, quoting contamination
      as the predominant source. To summarize the available evidence to date, a
      systematic review and meta-analysis was conducted. METHODS: A comprehensive
      search from 6 electronic databases was performed for studies investigating the
      potential relationship between disc infection as a cause for degenerative disc
      disease and symptomatic neck/back pain or radiculopathy. Random-effects meta
      analysis of proportions and odds ratio with 95% confidence intervals was used to
      pool the available evidence. RESULTS: Nine relevant studies involving 602
      patients with degenerative disc disease or pain were identified. From 6 studies
      supporting the role of infection in the pathophysiology of disc degeneration, the
      pooled infection prevalence was 45.2% (34.5%-56.0%). Overall pooled prevalence in
      all studies was 36.2% (24.7%-47.7%). Proportion of disc infections was higher in
      patients with symptomatic disc disease than in patients without (37.4% vs. 5.9%;
      odds ratio, 6.1; 95% confidence intervals, 1.426-25.901). The majority of
      infections were due to Propionibacterium acnes in 59.6% (43.2%-76.1%).
      CONCLUSION: From the limited evidence available, the possibility that disc
      infection may be linked with disc degeneration should not be ruled out. There is
      a need to investigate this further through larger, adequately powered multi
      institutional studies with contaminant arm to control for specimen contamination.
      LEVEL OF EVIDENCE: 2.

PMID- 25955095
TI  - Dysfunctional microcirculation of the lumbar vertebral marrow prior to the bone
      loss and intervertebral discal degeneration.
AB  - STUDY DESIGN: Descriptive study, stratified sampling. OBJECTIVE: Using dynamic
      computed tomographic perfusion (CTP) to explore the age-related distribution
      patterns of the microcirculation perfusion in the vertebral marrow, the vertebral
      bone mineral density (BMD), and the intervertebral discal degeneration (IDD)
      further to discuss the possible causation between them. SUMMARY OF BACKGROUND
      DATA: A latest viewpoint deemed that reduced blood supply of the vertebral marrow
      was correlated with an increased incidence of IDD and loss of BMD. However, the
      causative relationship between them needs more investigation. METHODS: One
      hundred eighty-six general people were randomly enrolled by stratified sampling
      and grouped by age: 15 years or less, 16 to 25 years, 26 to 35 years, 36 to 45
      years, 46 to 55 years, 56 to 65 years, 66 to 75 years, and 76 years or more. Both
      CTP and BMD of the third and fourth lumbar vertebral marrow were measured, and
      the IDD incidence of the third-fourth vertebrae was assessed. The temporal
      spatial distribution patterns of the age-related changes of CTP, BMD, and IDD
      were described, and the correlations between them were calculated. RESULTS:
      Microcirculatory perfusion of the vertebral marrow developed to maturate by 25
      years, maintained stable at 35 years, and then declined by age after 35 years.
      BMD grew to a peak phase in 26 to 45 years and then dropped by years. However,
      IDD presented a sudden increase after 45 years of age. CTP (blood flow [r=0.806],
      blood volume [r=0.685], and permeability [r=0.619]) showed strong positive
      correlations and CTP (time to peak [r=-0.211], mean transit time [r=-0.598])
      showed negative correlations with BMD. Meanwhile, CTP (blood flow [r=-0.815],
      blood volume [r=-0.753], and permeability [r=-0.690]) had strong negative
      correlations and CTP (time to peak [r=0.323] and mean transit time [r=0.628]) had
      positive correlations with the incidence of IDD. CONCLUSION: Aging-related
      decrease of the microcirculatory perfusion of the lumbar vertebral marrow
      preceded the loss of BMD and the onset of IDD, indicating their possible causal
      relationship. LEVEL OF EVIDENCE: 3.

PMID- 25955096
TI  - Effect of denosumab on recurrent giant cell reparative granuloma of the lumbar
      spine.
AB  - STUDY DESIGN: A case of recurrent giant cell reparative granuloma (GCRG) of the
      lumbar spine successfully treated with denosumab is reported; a fully human
      monoclonal antibody against the receptor activator of nuclear factor kappa B
      (RANK) ligand (RANKL). OBJECTIVE: To report the first case of recurrent GCRG of
      the lumbar spine treated with denosumab. SUMMARY OF BACKGROUND DATA: GCRG is a
      non-neoplastic osteofibrous lesion usually found in the maxilla and mandible but
      rarely in the spine. It is clinically distinct from giant cell tumor of bone
      (GCTB), although common histological characteristics such as the proliferation of
      spindle-shaped stromal cells and multinucleated giant cells are shared. Denosumab
      has recently been reported to be effective for unresectable GCTB; however, there
      is only one report of its effect on GCRG. Moreover, the effect of denosumab on
      GCRG of the spine is unknown. METHODS: The clinical course, radiological
      features, pathology, and treatment outcome of a patient with recurrent GCRG of
      the lumbar spine treated with denosumab are documented. RESULTS: Denosumab
      treatment was used for this patient with unresectable recurrent GCRG of the
      lumbar spine. Follow-up lumbar radiography showed significant bone formations in
      the tumor lesion after 3 months of treatment. On follow-up computerized
      tomography scans of the L2 and L3 vertebral lesions, the replacement of
      osoteolytic lesions by the formation of cortical-like bone tissue was clearly
      identified. CONCLUSION: We report the first case of recurrent GCRG of the spine
      successfully treated with denosumab. Treatment with denosumab induced significant
      bone formation in the unresectable lumbar lesion with stable clinical improvement
      during the 12-month follow-up period without apparent complications. Denosumab
      shows promise as a new alternative treatment option for osteoclastic giant cell
      rich tumors, such as GCRG, especially for unresectable lesions of the spine.
      LEVEL OF EVIDENCE: 4.

PMID- 25955097
TI  - Prognostic implications of thymidylate synthase gene polymorphisms in patients
      with advanced small bowel adenocarcinoma treated with first-line fluoropyrimidine
      based chemotherapy.
AB  - Thymidylate synthase (TS) gene polymorphisms such as tandem repeat (TR)
      polymorphisms and single-nucleotide polymorphisms (SNPs) affect transcriptional
      efficiency of the TS gene and may be prognostic markers for fluoropyrimidine
      based therapy in various gastrointestinal cancers. However, data for TS
      polymorphisms on clinical outcomes in advanced small bowel adenocarcinoma (SBA)
      are limited. We retrospectively enrolled 58 locally advanced/metastatic SBA
      patients treated with first-line fluoropyrimidine-based chemotherapy and analyzed
      the relationship between TS genotypes and clinical outcomes in 30 patients who
      were available for tumor tissue. Based on TR polymorphisms and a G>C SNP in the
      promoter region of the TS gene, 74% of patients had high TS expression genotypes
      (2R/3RG, 3RG/3RC, 3RG/3RG); the remainder had low TS expression genotypes (2R/2R,
      2R/3RC, 3RC/3RC). After a median follow-up of 48.8 months, median progression
      free survival (PFS) and overall survival (OS) in all patients were 6.0 and 11.3
      months, respectively. However, patients with low TS expression genotypes had
      better median PFS (12.8 vs. 4.3 months, P=0.027) and OS (28.8 vs. 8.9 months,
      P=0.025) than those with high TS expression genotypes. In multivariate analysis,
      poor Eastern Cooperative Oncology Group performance status [hazard ratio (HR),
      2.85; 95% CI, 1.02-7.93] and high TS expression genotypes (HR, 3.49; 95% CI, 1.13
      10.78) were independent prognostic factors for worse OS. Therefore, TS genotypes,
      based on a G>C SNP in the TR sequence of the TS gene, may be a useful biomarker
      for predicting outcomes for fluoropyrimidine-based chemotherapy in patients with
      locally advanced/metastatic SBA. 

PMID- 25955098
TI  - The Nature's Clever Trick for Making Cyclic Dinucleotide.
AB  - Ever since their initial discovery few years ago, cyclic dinucleotides (cDNs),
      their biosynthesis, and their biological function have been in focus of intense
      research efforts. In this issue, Kato et al. (2015) present strong evidence that
      the key enzyme in cDN biosynthesis, DncV, is poised on a tipping point such that,
      given a nudge, the enzyme, can link the nucleotides into a distinct cyclic loop,
      leading to a specific innate immune response. 

PMID- 25955099
TI  - Bending membranes into different shapes.
AB  - BAR domains bend membranes by imposing their curved shape. In this issue, Isas et
      al. show the structural differences in the interaction of the BAR domain protein
      amphiphysin with vesicles and tubes. They find that superficial interactions lead
      to vesicles, whereas more penetrating interactions of a more crowded protein lead
      to tubes. 

PMID- 25955100
TI  - The Beauty of a Visualized Peroxo-diiron(III) Intermediate.
AB  - Deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH) are essential
      for hypusination of eukaryotic translation initiation factor 5A (eIF-5A). In this
      issue, Han et al. use X-ray crystallograpy and UV/Vis and Mossbauer spectroscopy
      to provide insights into the fundamental mechanism of the hypusination of eIF-5A
      and a peroxo intermediate state. 

PMID- 25955101
TI  - AppCiter: A Web Application for Increasing Rates and Accuracy of Scientific
      Software Citation.

PMID- 25955102
TI  - Tumor growth delay by adjuvant alternating electric fields which appears non
      thermally mediated.
AB  - Delivery of the so-called Tumor Treatment Fields (TTFields) has been proposed as
      a cancer therapy. These are low magnitude alternating electric fields at
      frequencies from 100 to 300 kHz which are applied continuously in a non-invasive
      manner. Electric field delivery may produce an increase in temperature which
      cannot be neglected. We hypothesized that the reported results obtained by
      applying TTFields in vivo could be due to heat rather than to electrical forces
      as previously suggested. Here, an in vivo study is presented in which pancreatic
      tumors subcutaneously implanted in nude mice were treated for a week either with
      mild hyperthermia (41  degrees C) or with TTFields (6 V/cm, 150 kHz) and tumor
      growth was assessed. Although the TTFields applied singly did not produce any
      significant effect, the combination with chemotherapy did show a delay in tumor
      growth in comparison to animals treated only with chemotherapy (median relative
      reduction=47%). We conclude that concomitant chemotherapy and TTFields delivery
      show a beneficial impact on pancreatic tumor growth. Contrary to our hypothesis,
      this impact is non-related with the induced temperature increase.

PMID- 25955103
TI  - Stem-cell angiogenesis and regeneration of the heart: review of a saga of 2
      decades.
AB  - Advances in the novel approach to control ischemic heart disease and heart
      failure using stem cells or progenitor cells from bone marrow, mesenchyme, or
      myocardial tissue itself have demonstrated efficacy for increasing left
      ventricular function, decreasing infarct scar tissue, improving exercise
      tolerance and heart failure symptoms, and, in some studies, decreasing mortality
      and reducing rehospitalization for intractable angina or subsequent myocardial
      infarction. The most common techniques utilize injections of cells into the
      coronary vasculature or directly into specific areas of vulnerable myocardium.
      Although few adverse effects have been noted in clinical trials of these
      procedures, further clinical trials over the next decade should provide further
      advances in interventional techniques, ancillary supporting technologies to
      enhance cell regeneration, and applications in ischemic heart disease,
      cardiomyopathies, and cardiac genetic disorders. 

PMID- 25955105
TI  - Poor cell block adequacy rate for molecular testing improved with the addition of
      Diff-Quik-stained smears: Need for better cell block processing.
AB  - BACKGROUND: In the era of personalized medicine, requests for molecular testing
      of specimens obtained with minimally invasive procedures such as fine-needle
      aspiration have been increasing. Although cell blocks (CBs) are the recommended
      specimens for molecular testing, their performance has not been well analyzed.
      The objective of this study was to assess the frequency and types of samples
      deemed unsatisfactory for molecular testing (quantity not sufficient [QNS]).
      METHODS: One year after the implementation of careful monitoring of QNS cases,
      cases submitted for lung cancer molecular testing were analyzed for the QNS rate.
      When the cases were rejected for the inadequacy of CBs of cytology specimens, air
      dried, Diff-Quik (DQ)-stained smears were reviewed and used if they were
      adequate. The QNS rates were compared across 4 specimen categories: large
      resection, small biopsy, CB alone, and CB with DQ smears. RESULTS: One hundred
      seventy-six cases were studied, and 45 (25.6%) were unsatisfactory. Only 1 of 73
      large resection specimens was rejected because of decalcification. The QNS rate
      for small biopsy specimens was 35.9% (28 of 78), whereas 64% (16 of 25) of
      cytology cases ordered on CBs were rejected. In combination with DQ smears, the
      QNS rate of cytology specimens was 32% (8 of 25), which was a significant
      improvement over CBs only (P = .024) and was not significantly different from the
      QNS rate for small biopsies (P = .671). CONCLUSIONS: The utilization of DQ
      stained smears for molecular testing improves the adequacy of cytologic samples
      and provides a minimally invasive alternative to surgical biopsy when molecular
      analysis of tumor material is necessary.

PMID- 25955104
TI  - FOXQ1 mediates the crosstalk between TGF-beta and Wnt signaling pathways in the
      progression of colorectal cancer.
AB  - A wide variety of signaling transduction pathways contribute to tumorigenesis.
      Forkhead box Q1 (FOXQ1) is a member of the forkhead transcription factor family
      and its upregulation is closely correlated with tumor progression and prognosis
      of multiple cancer types, including colorectal cancer. However, the molecular
      mechanisms by which FOXQ1 promotes tumorigenesis, especially cancer cell invasion
      and metastasis in colorectal cancer, have not been fully elucidated. In the
      present study, we demonstrate that FOXQ1 is overexpressed in colorectal tumor
      tissues and its expression level is closely correlated with the stage and lymph
      node metastasis of colorectal cancer. In in vitro cultured SW480 colorectal
      cancer cells, knockdown of FOXQ1 expression by small interfering RNA greatly
      diminished the aggressive tumor behaviors of SW480 cells, including angiogenesis,
      invasion, epithelial-mesenchymal transition, and resistance to chemotherapy drug
      induced apoptosis. Further mechanistic investigation showed that FOXQ1 silencing
      prevents the nuclear translocation of beta-catenin, thus reducing the activity of
      Wnt signaling. Moreover, TGF-beta1 induced the expression of FOXQ1 as well as the
      migration and invasion of SW480 cells, which was partially prevented following
      knockdown of FOXQ1. Our results demonstrate that FOXQ1 plays a critical role
      during the tumorigenesis of colorectal cancer and is a mediator of the crosstalk
      between Wnt and TGF-beta signaling pathways. Our findings provide further insight
      into the cancer biology of colorectal cancer and suggest that FOXQ1 is a
      potential therapeutic target for the development of therapies for colorectal
      cancer. 

PMID- 25955107
TI  - Combination of the multipotent mesenchymal stromal cell transplantation with
      administration of temozolomide increases survival of rats with experimental
      glioblastoma.
AB  - Glioblastoma multiforme (GM) is an aggressive malignant tumor of the brain. The
      standard treatment of GM is surgical resection with consequent radio- and
      chemotherapy with temozolomide. The prognosis is unfavorable, with a survival
      time of 12-14 months. The phenomenon of targeted migration to the tumor in the
      brain opens novel possibilities for the treatment of GM. Multipotent mesenchymal
      stromal cells (MMSCs) are a cell type with anti-carcinogenic properties and can
      be used to optimize GM therapy. The aim of the present study was to investigate
      the effects of MMSC transplantation in the chemotherapy of a rat model of C6
      glioma. A total of 130 animals were divided into a control group, a temozolomide
      group, MMSCs group and temozolomide + MMSCs group. The experiment was performed
      over 70 days, and a combination of molecular biology, surgical and neuroimaging
      techniques, as well as histological and physiological examinations was used.
      Tumor size was smallest in the temozolomide (115.76 +/- 16.25 mm(3)) and in
      temozolomide + MMSCs (114.74 +/- 5.54 mm(3)) groups, which was significantly
      smaller than the neoplastic node size in the control group (202.09 +/- 39.72
      mm(3)) (P<0.05). The animals in the temozolomide + MMSCs group showed
      significantly higher survival rates in comparison with those in the control and
      temozolomide groups. The MMSCs migrated from the site of implantation to the
      neoplastic focus and interacted with glioma cells; however, the mechanism
      requires further research. In conclusion, MMSC transplantation combined with
      temozolomide treatment significantly extended the survival of experimental
      animals in comparison with those treated with temozolomide only.

PMID- 25955111
TI  - miR-494 suppresses the progression of breast cancer in vitro by targeting CXCR4
      through the Wnt/beta-catenin signaling pathway.
AB  - Breast cancer is the most common cancer among women with a high mortality
      worldwide, which is mainly due to tumor invasion and metastasis. Previous studies
      have reported that microRNA-494 (miR-494) is downregulated in breast cancer
      cells. The present study investigated the role of miR-494 in the progression of
      breast cancer and the underlying mechanisms. The levels of miR-494 were analyzed
      in several breast cancer cell lines by quantitative reverse transcription PCR
      (qRT-PCR). The miR-494 mRNA levels were significantly lower in the malignant
      breast cancer cells than the level in the non-malignant normal breast epithelial
      cells. miR-494 mimic transfection upregulated the expression levels of E
      cadherin, yet downregulated N-cadherin, vimentin and alpha-smooth muscle actin
      (alpha-SMA) in the breast cancer cells. As expected, the expression of these
      markers in breast cancer cells transfected with miR-494 inhibitors exhibited the
      opposite variation trend. MTT and Transwell assays showed that cell proliferation
      and invasion were both significantly suppressed by miR-494 mimics, and were
      significantly promoted by miR-494 inhibitors. The protein expression level of
      chemokine (C-X-C motif) receptor 4 (CXCR4) in the breast cancer cells was
      significantly inhibited by miR-494 mimics, and enhanced by miR-494 inhibitors.
      Yet, the mRNA level of CXCR4 was barely affected by miR-494 mimics or inhibitors.
      Dual-luciferase assay confirmed that miR-494 directly interacted with the 3'
      untranslated region of CXCR4 mRNA by dual-luciferase assay. The miR-494 mimics
      also significantly inhibited the transcription levels of beta-catenin, LEF1, CD44
      and cyclin-D1, which was similar to the effect of siRNA targeted to CXCR4. In
      conclusion, miR-494 suppresses the progression of breast cancer through the
      Wnt/beta-catenin signaling pathway, which is mediated by CXCR4.

PMID- 25955106
TI  - Increased Viral Dissemination in the Brain and Lethality in MCMV-Infected, Dicer
      Deficient Neonates.
AB  - Among Herpesviruses, Human Cytomegalovirus (HCMV or HHV-5) represents a major
      threat during congenital or neonatal infections, which may lead to encephalitis
      with serious neurological consequences. However, as opposed to other less
      prevalent pathogens, the mechanisms and genetic susceptibility factors for CMV
      encephalitis are poorly understood. This lack of information considerably reduces
      the prognostic and/or therapeutic possibilities. To easily monitor the effects of
      genetic defects on brain dissemination following CMV infection we used a recently
      developed in vivo mouse model based on the neonatal inoculation of a MCMV
      genetically engineered to express Luciferase. Here, we further validate this
      protocol for live imaging, and demonstrate increased lethality associated with
      viral infection and encephalitis in mutant mice lacking Dicer activity. Our data
      indicate that miRNAs are important players in the control of MCMV pathogenesis
      and suggest that miRNA-based endothelial functions and integrity are crucial for
      CMV encephalitis. 

PMID- 25955112
TI  - Daily life consequences, cognitive impairment, and fatigue after transient
      ischemic attack.
AB  - OBJECTIVES: Studies suggest that fatigue and cognitive impairment may be present
      after transient ischemic attack (TIA), but little is known about consequences in
      daily life. The main aim was to longitudinally explore the presence of fatigue,
      cognitive impairment, and consequences in daily life including communication
      after clinically diagnosed TIA at 1 and 9 months after the event. MATERIAL AND
      METHODS: A consecutive sample of 46 patients (23 women, 69 +/- 12.3 years) was
      assessed at discharge from hospital and at 1 and 9 months after TIA regarding
      cognition, mental fatigue, tiredness, and activities of daily life. This served
      as basis for an interview concerning experienced changes related to the TIA.
      RESULTS: Problems in daily life with probable association with the TIA were
      experienced by 37% (n = 45) of participants 9 months after the TIA event.
      Cognitive impairment was present in 40% (n = 44) after 1 month and 30% (n = 23)
      after 9 months. Mental fatigue was experienced by 26% (n = 42) after 1 month and
      17% (n = 39) after 9 months. Communication problems were reported and increased
      from 7 to 14 participants between the two time points. CONCLUSIONS: A third of
      the TIA patients experienced problems in performance of complex activities in
      daily life and often communication problems within the first 9 months. Cognitive
      impairment and mental fatigue could be factors influencing performance in daily
      life and at work, but this needs to be verified in a larger sample. The risk of
      activity limitations indicates need for multiprofessional support and systematic
      routines for TIA follow-up.

PMID- 25955113
TI  - Assistive technology access and service delivery in resource-limited
      environments: introduction to a special issue of Disability and Rehabilitation:
      Assistive Technology.
AB  - This special issue addresses access to and service delivery of assistive
      technology (AT) in resource-limited environments (RLEs). Access to AT is
      complicated not simply by limited funds to purchase AT, but by larger ecosystem
      weaknesses in RLEs related to legislation and policy, supply, distribution, human
      resources, consumer demand and accessible design. We present eight diverse
      articles that address various aspects of the AT ecosystem. These articles
      represent a wide range of AT, many different countries and different research
      methods. Our goal is to highlight a topic that has received scant research
      investigation and limited investment in international development efforts, and
      offer an insight into how different countries and programs are promoting access
      to AT. We encourage researchers, funders and non-profit organizations to invest
      additional effort and resources in this area. 

PMID- 25955114
TI  - Inpatient physical therapy rehabilitation provided for a patient with complete
      vision loss following a traumatic brain injury.
AB  - BACKGROUND: Data from the World Health Organization estimates the global
      incidence of traumatic brain injury resulting in hospitalization or mortality to
      be close to 10 million people each year. People who sustain a blast-related TBI
      are more likely to sustain visual impairment than people injured by other means.
      There is a lack of published literature regarding the most effective means to
      assist a patient's recovery from TBI with new vision loss. The aim of this report
      is to describe the physical therapy management of a person regaining functional
      mobility when newly blind following a blast-related TBI. METHOD: This case report
      describes the inpatient rehabilitation physical therapy (PT) services provided
      for a single subject who experienced a blast-related TBI with complete vision
      loss. OUTCOMES: The subject spent 3.5 weeks in IPR and participated in 21 PT
      sessions before being discharged home. Improvements in cognition, transfers and
      functional mobility with adaptations for vision loss were achieved, as well as
      caregiver training, to provide 24-hour supervision in the home. DISCUSSION:
      Collaborating with a blind specialist teacher assisted the rehabilitation of this
      subject. Further research is needed regarding the effective interventions for
      those with TBI and vision loss.

PMID- 25955115
TI  - Caregivers' support needs and factors promoting resiliency after brain injury.
AB  - AIM: This article explores the challenges, support needs and coping strategies of
      caregivers of people with an acquired brain injury (ABI). METHOD: Semi-structured
      interviews were conducted with caregivers (n = 20) to explore their support
      services received, access barriers, utility of services, needed supports, coping
      strategies and factors promoting life satisfaction. The team recorded,
      transcribed verbatim and inductively analysed all interviews. RESULTS: Through
      thematic data analysis, three central themes were revealed: (a) barriers impeding
      quality-of-life, (b) support needed to improve quality-of-life and (c) factors
      enabling quality-of-life. All perspectives from the participants involved are
      synthesized to provide a rich depiction of caregivers' support needs and coping
      strategies. CONCLUSIONS: Two specific findings of interest include a negative
      association between severity of brain injury and caregiver's desire to direct
      treatment, as well as a distinct service gap in assistance for caregivers who are
      caring for someone with violent/offending behaviours. This study recommends short
      and long-term changes, given Australia's upcoming National Disability Insurance
      Scheme, to increase caregiver quality-of-life, which will ultimately affect the
      rehabilitation outcomes of persons with ABI.

PMID- 25955116
TI  - Text-to-speech accommodations for the reading challenges of adults with traumatic
      brain injury.
AB  - OBJECTIVE: This study's purpose was two-fold: (a) to confirm differences in
      silent reading rates of individuals with and without traumatic brain injury (TBI)
      and (b) to determine the effect of text-to-speech (TTS) on reading comprehension
      and efficiency by individuals with TBI. DESIGN AND METHODS: Ten adults with
      severe TBI answered comprehension questions about written passages presented in
      three conditions: reading only (RO), listening to TTS presentation only (LO) or
      reading and listening to TTS simultaneously (RL). The researchers compared
      reading rate, comprehension accuracy and comprehension rate (efficiency) across
      conditions. RESULTS: Analysis revealed significantly slower silent reading rates
      for the participants with TBI than for readers without TBI (n = 75). Also,
      participants with TBI achieved higher comprehension accuracy for factual than
      inferential questions; however, no significant main effect for comprehension
      accuracy emerged across reading conditions. In contrast, using comprehension rate
      as the dependent measure, analysis confirmed a significant main effect for
      reading condition and question type; post-hoc pairwise comparisons revealed that
      the RL condition yielded higher comprehension rate scores than the RO condition.
      CONCLUSIONS: As a group, adults with TBI appear to benefit in reading efficiency
      when simultaneously listening to and reading written passages; however,
      differences exist that reinforce the importance of individualizing treatment.

PMID- 25955118
TI  - Characterization of acute stress reaction following an IED blast-related mild
      traumatic brain injury.
AB  - PRIMARY OBJECTIVE: To characterize an acute stress reaction (ASR) following an
      improvised explosive device (IED) blast-related mild traumatic brain injury
      (mTBI). RESEARCH DESIGN: Participants were male, US military personnel treated in
      Afghanistan within 4 days following an IED-related mTBI event (n = 239). METHODS
      AND PROCEDURES: Demographics, diagnosis of ASR, injury history and self-reported
      mTBIs, blast exposures and psychological health histories were recorded. MAIN
      OUTCOMES AND RESULTS: In total, 12.5% of patients met ASR criteria. Patients with
      ASR were significantly younger and junior in rank (p < 0.05). Patients with ASR
      were more likely to experience the IED-blast while dismounted, report a loss of
      consciousness (LOC) and higher pain levels (p < 0.05). Adjusting for age and
      rank, multivariate logistic regression showed an association between mTBI history
      and ASR (AOR = 1.405; 95% CI = 1.105-1.786, p < 0.01). Adjusting for mechanism of
      injury (dismounted vs. mounted), LOC and pain, multivariate logistic regression
      showed an association between mTBI history and ASR (AOR = 1.453; 95% CI = 1.132
      1.864, p < 0.01). Prior blast exposure and past psychological health issues were
      not associated with ASR. CONCLUSIONS: A history of multiple mTBIs is associated
      with increased risk of ASR. Future research is warranted.

PMID- 25955117
TI  - Serum visinin-like protein-1 in concussed professional ice hockey players.
AB  - PRIMARY OBJECTIVE: Visinin-like protein-1 (VILIP-1) has shown potential utility
      as a biomarker for neuronal injury in cerebrospinal fluid. This study
      investigated serum VILIP-1 as a diagnostic and prognostic marker in sports
      related concussion. METHODS: This multi-centre prospective cohort study involved
      the 12 teams of the professional ice hockey league in Sweden. A total of 288
      players consented to participate in the study. Thirty-five players sustained
      concussions, of whom 28 underwent repeated blood samplings at 1, 12, 36 and 144
      hours after the trauma or when the player returned to play (7-90+ days). MAIN
      OUTCOMES AND RESULTS: The highest levels of VILIP-1 were measured 1 hour after
      concussion and the levels decreased during rehabilitation, reaching a minimum
      level at the 36-hour sampling. However, the levels of serum VILIP-1 at 1 hour
      after concussion were not significantly higher than pre-season baseline values.
      Serum levels of VILIP-1 1 hour post-concussion did not correlate with the number
      of days for the concussion symptoms to resolve. Further, serum levels of VILIP-1
      increased after a friendly game in players who were not concussed. CONCLUSIONS:
      These results provide evidence that serum VILIP-1 may not be a useful biomarker
      for diagnosis and prognosis of sports-related concussion.

PMID- 25955120
TI  - Identification of lymphatic metastasis-associated genes in a metastatic ovarian
      cancer cell line.
AB  - Ovarian cancer (OC) is the gynecological malignancy with the highest rate of
      mortality, and lymphatic metastasis is a critical factor in disease recurrence
      and prognosis. In the current study, the SKOV-3/LN403 cell line, which has high
      potential for lymph node metastasis was established as a result of four rounds of
      selection from retroperitoneal lymph nodes following intraperitoneal injections
      of SKOV-3 ovarian adenocarcinoma cells. In comparison to the parental SKOV-3 cell
      line, SKOV-3/LN403 has a higher rate of proliferation, is more invasive and
      exhibits greater resistance to paclitaxel. Subsequently, a novel animal model of
      OC lymphatic metastasis was developed with SKOV-3/LN403 cells and a high
      incidence of positive metastatic lymph nodes, peritoneal dissemination and bloody
      ascites were observed, which mimicked the clinical outcome of patients with OC.
      Analysis of the gene expression profiles of SKOV-3 and SKOV-3/LN403 cells
      identified several genes and pathways that may be involved in lymphatic
      metastasis of OC. The induction of focal adhesion kinase expression provides a
      potential therapeutic target for OC lymphatic metastasis.

PMID- 25955119
TI  - Falls in young children with minor head injury: A prospective analysis of injury
      mechanisms.
AB  - BACKGROUND: Fall is a common mechanism of injury (MOI) in young children and an
      important risk factor for traumatic brain injury (TBI). Most children who fall
      have a minor head injury (MHI), defined as a blunt head trauma that occurred in a
      patient who is conscious and responsive. OBJECTIVE: To seek a possible
      association between MOI and injury severity. METHODS: A single centre cohort
      study was conducted. Data were collected on patients aged 0-2 years with MHI.
      Clinically-significant TBI (csTBI), defined as head injury resulting in death,
      intubation or neurosurgery, was the primary outcome measure. Traumatic finding on
      CT scan (TFCT) was the secondary outcome measure. RESULTS: Five hundred and
      ninety-five patients were analysed. Eight types of falls were identified: from
      ground-level, down stairs, from a bed, from a changing table, from furniture,
      from adult-hold, from a playground-device and from a stroller/baby-carriage. One
      patient (0.16%) had csTBI. Thirty-one (5.2%) underwent CT scans, TFCT was
      diagnosed in 17 (2.8%) patients; 10 (1.7%) linear skull-fractures, two (0.3%)
      depressed skull-fractures and five (0.8%) intracranial haemorrhages. Regression
      analysis did not reveal a statistically significant association between any of
      the MOI and the presence of TFCT. CONCLUSIONS: The risk for csTBI was low and no
      association was found between MOI and injury severity.

PMID- 25955121
TI  - Understanding forces in biofilms.

PMID- 25955123
TI  - PEGylated graphene oxide for tumor-targeted delivery of paclitaxel.
AB  - AIM: The graphene oxide (GO) sheet has been considered one of the most promising
      carbon derivatives in the field of material science for the past few years and
      has shown excellent tumor-targeting ability, biocompatibility and low toxicity.
      We have endeavored to conjugate paclitaxel (PTX) to GO molecule and investigate
      its anticancer efficacy. MATERIALS & METHODS: We conjugated the anticancer drug
      PTX to aminated PEG chains on GO sheets through covalent bonds to get GO-PEG-PTX
      complexes. The tissue distribution and anticancer efficacy of GO-PEG-PTX were
      then investigated using a B16 melanoma cancer-bearing C57 mice model. RESULTS:
      The GO-PEG-PTX complexes exhibited excellent water solubility and
      biocompatibility. Compared with the traditional formulation of PTX (Taxol(r)), GO
      PEG-PTX has shown prolonged blood circulation time as well as high tumor
      targeting and -suppressing efficacy. CONCLUSION: PEGylated graphene oxide is an
      excellent nanocarrier for paclitaxel for cancer targeting.

PMID- 25955122
TI  - Hollow mesoporous silica nanoparticles for tumor vasculature targeting and PET
      image-guided drug delivery.
AB  - AIM: Development of multifunctional and well-dispersed hollow mesoporous silica
      nanoparticles (HMSNs) for tumor vasculature targeted drug delivery and PET
      imaging. MATERIALS & METHODS: Amine functionalized HMSNs (150-250 nm) were
      conjugated with a macrocyclic chelator, (S)-2-(4-isothiocyanatobenzyl)-1,4,7
      triazacyclononane-1,4,7-triaceticacid (NOTA), PEGylated and loaded with
      antiangiogenesis drug, Sunitinib. Cyclo(Arg-Gly-Asp-D-Tyr-Lys) (cRGDyK) peptide
      was attached to the nanoconjugate and radiolabeled with (64)Cu for PET imaging.
      RESULTS: (64)Cu-NOTA-HMSN-PEG-cRGDyK exhibited integrin-specific uptake both in
      vitro and in vivo. PET results indicated approximately 8% ID/g uptake of targeted
      nanoconjugates in U87MG tumors, which correlated well with ex vivo and
      histological analyses. Enhanced tumor-targeted delivery of sunitinib was also
      observed. CONCLUSION: We successfully developed tumor vasculature targeted HMSNs
      for PET imaging and image-guided drug delivery.

PMID- 25955124
TI  - Effect of cerium oxide nanoparticles on sepsis induced mortality and NF-kappaB
      signaling in cultured macrophages.
AB  - AIM: To investigate whether cerium oxide (CeO2) nanoparticles could be used for
      the treatment of severe sepsis. MATERIALS & METHODS: Cecal peritonitis was
      induced in male Sprague-Dawley rats in the presence and absence of CeO2
      nanoparticles. Cultured macrophages (RAW264.7 cells) were challenged with
      lipopolysaccharide in the absence and presence of CeO2 nanoparticles. The effect
      of nanoparticles on the growth of Escherichia coli and Staphylococcus aureus was
      determined in culture. RESULTS: Nanoparticle treatment decreased sepsis-induced
      mortality, organ damage, serum IL-6, blood urea nitrogen and inflammatory
      markers. Nanoparticle treatment diminished lipopolysaccharide-induced cytokine
      release and p65-nuclear factor-KB (NF-KB) activation in cultured RAW264.7 cells.
      Exposure to CeO2 nanoparticles inhibited E. coli growth. CONCLUSION: The findings
      of this study indicate that CeO2 nanoparticles may be useful for the treatment of
      sepsis.

PMID- 25955125
TI  - Gold nanoparticle surface functionalization: a necessary requirement in the
      development of novel nanotherapeutics.
AB  - With several gold nanoparticle-based therapies currently undergoing clinical
      trials, these treatments may soon be in the clinic as novel anticancer agents.
      Gold nanoparticles are the subject of a wide ranging international research
      effort with preclinical studies underway for multiple applications including
      photoablation, diagnostic imaging, radiosensitization and multifunctional drug
      delivery vehicles. These applications require an increasingly complex level of
      surface modification in order to achieve efficacy and limit off-target toxicity.
      This review will discuss the main obstacles in relation to surface
      functionalization and the chemical approaches commonly utilized. Finally, we
      review a range of recent preclinical studies that aim to advance gold
      nanoparticle treatments toward the clinic. 

PMID- 25955126
TI  - Enhancing orthopedic implant bioactivity: refining the nanotopography.
AB  - Advances in nanotechnology open up new possibilities to produce biomimetic
      surfaces that resemble the cell in vivo growth environment at a nanoscale level.
      Nanotopographical changes of biomaterials surfaces can positively impact the
      bioactivity and ossointegration properties of orthopedic and dental implants.
      This review introduces nanofabrication techniques currently used or those with
      high potential for use as surface modification of biomedical implants. The
      interactions of nanotopography with water, proteins and cells are also discussed,
      as they largely determine the final success of the implants. Due to the well
      documented effects of surface chemistry and microtopography on the bioactivity of
      the implant, we here elaborate on the ability of the nanofabrication techniques
      to combine the dual (multi) modification of surface chemistry and/or
      microtopography. 

PMID- 25955127
TI  - Nanoparticle-based multimodal PET/MRI probes.
AB  - The integration of PET and MRI modalities into a single hybrid imaging system has
      been demonstrated to synergistically compensate for the limitations of each
      modality, with the potential to enhance diagnostic accuracy and improve
      development of therapeutics. To take advantage of the progress of the hybrid
      PET/MRI hardware, nanoparticle-based probes are being developed for multimodal
      applications. In this paper, recent advances in the development of nanoparticle
      based, multimodal PET/MRI probes are reviewed. Common MRI contrast agents, PET
      tracers and chelators and surface functionality that comprised PET/MRI nanoprobes
      reported in the last 10 years are summarized, followed by a description of the
      physical properties of these probes and their imaging applications. 

PMID- 25955128
TI  - Beyond passive immunization: toward a nanoparticle-based IL-17 vaccine as first
      in class of future immune treatments.
AB  - Nanoparticles occur naturally as part of repetitive molecular structures forming
      virus-like particles (VLPs). VLPs are powerful immune activators. Specifically,
      VLP can elicit a direct activation of B lymphocytes to trigger production of
      antibodies targeted at molecules chemically linked to the VLP. We here review
      recent data from genetics research, large-scale genomic sequencing, as well as
      clinical trials which suggest that a VLP-based vaccine against the signaling
      molecule IL-17 will be safe and effective in the common skin disease psoriasis,
      as well as other conditions. Active vaccination against IL-17 is capable of
      replacing the costly manufacture of antibodies currently in clinical use with
      huge implications for treatment availability and health economics.

PMID- 25955129
TI  - Feasibility and Acute Care Utilization Outcomes of a Post-Acute Transitional
      Telemonitoring Program for Underserved Chronic Disease Patients.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) and heart failure (HF)
      are chronic diseases that impart significant health and care costs to the patient
      and health system. Limited access to health services affects disease severity and
      functional status. Telemonitoring has shown promise in reducing acute care
      utilization for chronic disease patients, but the benefit for the underserved has
      not been determined. We evaluated acute care utilization outcomes following an
      acute event of a 90-day transitional care program integrating telemonitoring
      technology and home visits for underserved COPD and HF patients. MATERIALS AND
      METHODS: Patients were enrolled into the program between October 2010 and August
      2012. Primary outcomes included rates of emergency department (ED) visits and all
      cause re-admission at 30, 90, and 180 days postdischarge. Program and functional
      status at enrollment and discharge and satisfaction with telemonitoring at
      discharge were measured. Telemonitoring included daily symptomatology recording
      and was removed at 90 days. A control cohort was identified through electronic
      health records and propensity-matched via 15 variables to achieve a sample size
      with balanced baseline characteristics. RESULTS: Program patients showed 50%
      reduction in 30-day re-admission and 13-19% reduction in 180-day re-admission
      compared with control patients. There was no significant difference in ED
      utilization. Patients were satisfied with telemonitoring services, and functional
      status improved by program end. CONCLUSIONS: This feasibility study suggests
      telemonitoring in the context of a transitional care model following an acute
      event may reduce all-cause 30-day re-admissions by up to 50% and has the
      potential to reduce long-term acute care utilization and thus care costs. More
      rigorous and long-term investigation is warranted.

PMID- 25955130
TI  - Ab initio modeling of the bonding of benzotriazole corrosion inhibitor to reduced
      and oxidized copper surfaces.
AB  - The bonding of benzotriazole-an outstanding corrosion inhibitor for copper-on
      reduced and oxidized copper surfaces is discussed on the basis of density
      functional theory (DFT) calculations. Calculations reveal that benzotriazole is
      able to bond with oxide-free and oxidized copper surfaces and on both of them it
      bonds significantly stronger to coordinatively unsaturated Cu sites. This
      suggests that benzotriazole is able to passivate the reactive under-coordinated
      surface sites that are plausible microscopic sites for corrosion attack.
      Benzotriazole can adsorb in a variety of different forms, yet it forms a strong
      molecule-surface bond only in deprotonated form. The bonding is even stronger
      when the deprotonated form is incorporated into organometallic adcomplexes. This
      is consistent with existing experimental evidence that benzotriazole inhibits
      corrosion by forming protective organometallic complexes. It is further shown
      that adsorption of benzotriazole considerably reduces the metal work function,
      which is a consequence of a large permanent molecular dipole and a properly
      oriented adsorption structure. It is argued that such a pronounced effect on the
      work function might be relevant for corrosion inhibition, because it should
      diminish the anodic corrosion reaction, which is consistent with existing
      experimental evidence that benzotriazole, although a mixed type inhibitor,
      predominantly affects the anodic reaction. 

PMID- 25955131
TI  - Atomically thin group v elemental films: theoretical investigations of antimonene
      allotropes.
AB  - Group V elemental monolayers including phosphorene are emerging as promising 2D
      materials with semiconducting electronic properties. Here, we present the results
      of first-principles calculations on stability, mechanical and electronic
      properties of 2D antimony (Sb), antimonene. Our calculations show that free
      standing alpha and beta allotropes of antimonene are stable and semiconducting.
      The alpha-Sb has a puckered structure with two atomic sublayers and beta-Sb has a
      buckled hexagonal lattice. The calculated Raman spectra and STM images have
      distinct features thus facilitating characterization of both allotropes. The beta
      Sb has nearly isotropic mechanical properties, whereas alpha-Sb shows strongly
      anisotropic characteristics. An indirect-direct band gap transition is expected
      with moderate tensile strains applied to the monolayers, which opens up the
      possibility of their applications in optoelectronics. 

PMID- 25955132
TI  - Enhanced stability of blood matrices using a dried sample spot assay to measure
      human butyrylcholinesterase activity and nerve agent adducts.
AB  - Dried matrix spots are safer to handle and easier to store than wet blood
      products, but factors such as intraspot variability and unknown sample volumes
      have limited their appeal as a sampling format for quantitative analyses. In this
      work, we introduce a dried spot activity assay for quantifying
      butyrylcholinesterase (BChE) specific activity which is BChE activity normalized
      to the total protein content in a sample spot. The method was demonstrated with
      blood, serum, and plasma spotted on specimen collection devices (cards) which
      were extracted to measure total protein and BChE activity using a modified Ellman
      assay. Activity recovered from dried spots was ~80% of the initial spotted
      activity for blood and >90% for plasma and serum. Measuring total protein in the
      sample and calculating specific activity substantially improved quantification
      and reduced intraspot variability. Analyte stability of nerve agent adducts was
      also evaluated, and the results obtained via BChE-specific activity measurements
      were confirmed by quantification of BChE adducts using a previously established
      LC-MS/MS method. The spotted samples were up to 10 times more resistant to
      degradation compared to unspotted control samples when measuring BChE inhibition
      by the nerve agents sarin and VX. Using this method, both BChE activity and
      adducts can be accurately measured from a dried sample spot. This use of a dried
      sample spot with normalization to total protein is robust, demonstrates decreased
      intraspot variability without the need to control for initial sample volume, and
      enhances analyte stability. 

PMID- 25955134
TI  - Effect of DOM Size on Organic Micropollutant Adsorption by GAC.
AB  - Granular activated carbon (GAC) adsorption of the micropollutants 2
      methylisoborneol (MIB) and warfarin (WFN) at ng/L levels was investigated in five
      waters with isolated natural dissolved organic matter (DOM) held at a constant
      dissolved organic carbon concentration. Each water was evaluated for competitive
      adsorption effects based on the pretreatment of ultrafiltration, coagulation, and
      additional background micropollutants. Using the breakthrough with unfractionated
      DOM as a baseline, on average, the water with lower molecular weight (MW) DOM
      decreased MIB and WFN adsorption capacity by 59%, whereas the water with higher
      MW DOM increased MIB and WFN adsorption capacity by 64%. All waters showed
      similar decreasing MIB and WFN adsorption capacity with increasing empty bed
      contact time (EBCT), with more dramatic effects seen for the more strongly
      adsorbing WFN. On average, MIB and WFN adsorption kinetics were two times slower
      in the water with higher MW DOM compared to the water with lower MW DOM, as
      described by the intraparticle pore diffusion tortuosity. Increased adsorption
      competition from 27 micropollutants other than MIB and WFN at environmentally
      relevant concentrations had little to no effect on MIB and WFN breakthrough
      behavior. Any competitive effect from background micropollutants became
      indiscernible at longer EBCTs. 

PMID- 25955133
TI  - Sulforaphane reduces molecular response to hypoxia in ovarian tumor cells
      independently of their resistance to chemotherapy.
AB  - One of the recently emerging anticancer strategies is the use of natural dietary
      compounds, such as sulforaphane, a cancer-chemopreventive isothiocyanate found in
      broccoli. Based on the growing evidence, sulforaphane acts through molecular
      mechanisms that interfere with multiple oncogenic pathways in diverse tumor cell
      types. Herein, we investigated the anticancer effects of bioavailable
      concentrations of sulforaphane in ovarian carcinoma cell line A2780 and its two
      derivatives, adriamycin-resistant A2780/ADR and cisplatin-resistant A2780/CP cell
      lines. Since tumor microenvironment is characterized by reduced oxygenation that
      induces aggressive tumor phenotype (such as increased invasiveness and resistance
      to chemotherapy), we evaluated the effects of sulforaphane in ovarian cancer
      cells exposed to hypoxia (2% O2). Using the cell-based reporter assay, we
      identified several oncogenic pathways modulated by sulforaphane in hypoxia by
      activating anticancer responses (p53, ARE, IRF-1, Pax-6 and XRE) and suppressing
      responses supporting tumor progression (AP-1 and HIF-1). We further showed that
      sulforaphane decreases the level of HIF-1alpha protein without affecting its
      transcription and stability. It can also diminish transcription and protein level
      of the HIF-1 target, CA IX, which protects tumor cells from hypoxia-induced pH
      imbalance and facilitates their migration/invasion. Accordingly, sulforaphane
      treatment leads to diminished pH regulation and reduced migration of ovarian
      carcinoma cells. These effects occur in all three ovarian cell lines suggesting
      that sulforaphane can overcome the chemoresistance of cancer cells. This offers a
      path potentially exploitable in sensitizing resistant cancer cells to therapy,
      and opens a window for the combined treatments of sulforaphane either with
      conventional chemotherapy, natural compounds, or with other small molecules. 

PMID- 25955135
TI  - Development and characterization of drug-loaded biodegradable PLA microcarriers
      prepared by the electrospraying technique.
AB  - Biodegradable particles are extremely useful in the development of novel drug
      delivery systems. Recent studies have suggested that morphology can influence the
      mechanisms of drug delivery in many ways. In the present study, biodegradable
      microparticles with different morphologies were prepared from poly(L-lactide)
      (PLA) using the electrospraying technique. The microparticles were then
      systematically examined by scanning using an electron microscope. The results
      revealed that the preparation of drug-loaded microspheres through electrospraying
      is a simple and efficient method, and the processing parameters, such as polymer
      molecular weight, concentration, surfactant and solvent play an important role in
      obtaining high quality microcarriers. The association between microcarrier
      morphology and the processing parameters used was also investigated. Rifampin
      loaded PLA microspheres were also prepared according to the above-mentioned
      model. Our data demonstrate that the drug release from PLA microspheres can be
      sustained in vitro for over 60 h. Our study focused on obtaining electrosprayed
      medicated microparticles from complex polyester particles. Further studies are
      required to explore the potential commercial use of these microparticles.

PMID- 25955137
TI  - Radiographic distortion artifact of circular external fixators.
AB  - Circular external fixators are commonly used to surgically treat a variety of
      orthopedic conditions. However, distortion artifact may mislead the radiographic
      interpreter as to the true anatomic location of the transfixing wires and either
      negatively impact patient healing or lead to unnecessary procedures. Distortion
      is due to unequal magnification of different parts of an object. The purpose of
      this study was to assess distortion of three circular external fixator
      apparatuses with the transfixing wires at 30, 60, and 90 degrees . Distortion was
      greatest with all three apparatuses at 10 degrees  of rotation from parallel to
      the central X-ray beam. When comparing distortion between the three apparatuses,
      distortion was greatest with the transfixing wires at 30 degrees . The study
      authors concluded that distortion artifact is most severe when the transfixing
      wires are at smaller angles and when they are farther from the X-ray table. The
      circular external fixator should be placed in the center of, and parallel to, the
      primary X-ray beam and as close to the table as possible to reduce/prevent
      distortion artifact and possible radiographic misinterpretation of transfixing
      wire location. 

PMID- 25955138
TI  - Review of enterococci isolated from canine and feline urine specimens from 2006
      to 2011.
AB  - Canine and feline urine culture reports and medical records were reviewed at a
      veterinary teaching hospital from 2006 to 2011 for enterococcal growth,
      coinfections, antimicrobial resistance, urine sediment findings, clinical signs,
      and concurrent conditions. Of all of the urine specimens with significantly
      defined colony-forming units/mL, Enterococcus (E.) faecalis was the only
      enterococci isolated from cats and predominated (77.4%) in dogs followed by E.
      faecium (12.9%), E. durans (3.2%), and other Enterococcus spp. (6.5%). The
      majority of specimens with significant enterococcal growth resulted in
      complicated urinary tract infections in 83.9% of dogs and 81.8% of cats.
      Specimens with only enterococcal growth were more common than those mixed with
      other bacterial species. Cocci were observed in urine sediments of 8 out of 8
      cats and 21 out of 25 dogs with available concurrent urinalyses. Pyuria was noted
      in 5 out of 8 feline and 15 out of 25 canine urine sediments, and pyuria in dogs
      was associated with growth of only enterococci on aerobic urine culture.
      Multidrug resistance was identified in 6 out of 11 cats and 7 out of 31 dogs, and
      E. faecium isolates from dogs were 4.5* more likely to be multidrug resistant
      than E. faecalis.

PMID- 25955136
TI  - Deletion of the Neurotrophic Factor neudesin Prevents Diet-induced Obesity by
      Increased Sympathetic Activity.
AB  - Some neurotrophic factors, which are potent regulators of neuronal development
      and function, have recently been implicated in the control of energy balance by
      increasing energy expenditure. We previously identified neudesin as a novel
      neurotrophic factor with potential roles in the central nervous system. Although
      neudesin is also expressed in various peripheral tissues including adipose
      tissue, its physiological roles have not yet been elucidated. We found that
      neudesin knockout (KO) mice were resistant to high-fat diet-induced obesity and
      obesity-related metabolic dysfunctions. neudesin KO mice exhibited increased
      energy expenditure due to increased sympathetic activity, which resulted in
      increased heat production and fatty acid oxidation in brown adipose tissue and
      enhanced lipolysis in white adipose tissue. Thus, neudesin, which may be a
      negative regulator of sympathetic activity, could represent a novel regulator of
      the development of obesity and obesity-related metabolic dysfunctions. 

PMID- 25955139
TI  - Single-incision, laparoscopic-assisted jejunal resection and anastomosis
      following a gunshot wound.
AB  - A 2 yr old castrated male Pomeranian was evaluated for a 6 wk history of chronic
      vomiting, intermittent anorexia, and lethargy. Physical examination revealed a
      palpable, nonpainful, soft-tissue mass in the midabdominal area. Abdominal
      radiographs and ultrasound revealed a focal, eccentric thickening of the jejunal
      wall with associated jejunal mural foreign body and partial mechanical
      obstruction. Following diagnosis of a partial intestinal obstruction as the cause
      of chronic vomiting, the patient underwent general anesthesia for a laparoscopic
      assisted, midjejunal resection and anastomosis using a single-incision
      laparoscopic surgery port. The patient was discharged the day after surgery, and
      clinical signs abated according to information obtained during a telephone
      interview conducted 2 and 8 wk postoperatively. The dog described in this report
      is a unique case of partial intestinal obstruction treated by laparoscopic
      assisted resection and anastomosis using a single-incision laparoscopic surgery
      port. 

PMID- 25955140
TI  - Neuromuscular signs associated with acute hypophosphatemia in a dog.
AB  - The purpose of this report was to describe the successful recognition and
      management of neuromuscular dysfunction secondary to severe, acute
      hypophosphatemia in an adult dog with a 2 day history of vomiting, anorexia, and
      abdominal pain. Radiographs were suggestive of a foreign body obstruction, and
      surgery was recommended. Resection and anastomosis of the distal duodenum and
      proximal jejunum was performed. The dog recovered uneventfully, but approximately
      36 hr postoperatively, he was found to have significant weakness and muscle
      tremors that were accompanied by hyperthermia. The only significant abnormality
      on a serum biochemical profile was a phosphorous level of 0.26 mmol/L. Within 6
      hr of initiating phosphorous supplementation, the patient fully recovered and had
      no residual signs of neuromuscular dysfunction. Signs of neurologic dysfunction
      secondary to hypophosphatemia are commonly recognized in human patients. Reports
      of patients with severe muscle weakness, some of which necessitate ventilation
      due to weakening of muscles of respiration, are common throughout the literature.
      Less commonly, tremors are noted. This is the first known report of neuromuscular
      signs recognized and rapidly corrected in a dog. Although it is likely to be
      uncommon, hypophosphatemia should be recognized as a differential diagnosis in
      patients with tremors and/or muscle weakness.

PMID- 25955141
TI  - Acquired tricuspid valve stenosis associated with two ventricular endocardial
      pacing leads in a dog.
AB  - Acquired tricuspid valve stenosis (TVS) is a rare complication of endocardial
      pacing lead implantation in humans that has only been described once previously
      in the veterinary literature in a dog with excessive lead redundancy. A 12 yr old
      terrier presented with right-sided congestive heart failure 6 mo after
      implantation of a second ventricular endocardial pacing lead. The second lead was
      placed due to malfunction of the first lead, which demonstrated abnormally low
      impedance. Transthoracic echocardiography identified hyperechoic tissue
      associated with the pacing leads as they crossed the tricuspid valve annulus as
      well as a stenotic tricuspid inflow pattern via spectral Doppler interrogation.
      Medical management was ultimately unsuccessful and the dog was euthanized 6 wk
      after TVS was diagnosed. The authors report the first canine case of acquired TVS
      associated with two ventricular endocardial pacing leads. 

PMID- 25955142
TI  - Generalized canine discoid lupus erythematosus responsive to tetracycline and
      niacinamide therapy.
AB  - Discoid lupus erythematosus (DLE) is a commonly reported canine autoimmune
      disease that normally presents with a phenotype consisting of erythema,
      depigmentation, scaling, erosions/ulcers, and scarring over the nasal planum and
      the proximal dorsal muzzle. Recently, two cases of a generalized variant of this
      disease have been reported, whose lesions responded to either systemic
      glucocorticoids or a combination of topical corticosteroids, topical tacrolimus,
      and the oral antimalarial hydroxychloroquine. The purpose of this report is to
      describe an 11 yr old shih tzu that presented with skin lesions consisting of
      multiple annular, erythematous papules and plaques, hyperpigmentation, adherent
      scaling, and atrophic scars over the caudal dorsum, flanks, craniodorsal thorax,
      and lateroproximal extremities. A diagnosis of generalized DLE was made based on
      the clinical presentation, histopathology, laboratory values, and direct
      immunofluorescence findings. Treatment consisted of oral tetracycline and oral
      niacinamide, which resulted in complete remission of clinical signs. This is the
      first documented report of generalized canine DLE responding to the described
      immunomodulating regimen. Such a combination might therefore be considered as a
      glucocorticoid and/or antimalarial alternative for the management of generalized
      DLE. 

PMID- 25955143
TI  - Fatal venous air embolism during anesthesia in an apparently healthy adult
      Chihuahua.
AB  - An apparently healthy adult female Chihuahua was presented for elective
      ovariohysterectomy. After induction of general anesthesia, but prior to the start
      of the surgery, air was inadvertently administered to the patient via the i.v.
      fluid line. The patient convulsed, became apneic, arrested, and died despite
      attempted cardiopulmonary resuscitation. At necropsy, the pericardial sac was
      incised and filled with water to entirely submerge the intact heart. The right
      ventricular free wall was punctured, releasing several air bubbles from the right
      ventricle. Death was attributed to venous air embolism based on the clinical
      history, gross findings, and paucity of underlying gross and microscopic
      pathology that might have predisposed the dog to an anesthetic-related death. The
      discussion of this case includes a review of previously reported veterinary cases
      of fatal venous air embolism, including the varied mechanisms of embolus
      formation, the potential impact of pre-existing cardiopulmonary disease, and the
      methods used to detect emboli. This report outlines the events of fatal
      iatrogenic venous air embolization and emphasizes the importance of considering
      this entity in the case of sudden death of a patient with an indwelling catheter
      in order to pursue either appropriate diagnostic tests or necropsy techniques to
      aid in the diagnosis.

PMID- 25955144
TI  - Pancreatic abscess in a cat with diabetes mellitus.
AB  - An 11 yr old spayed female Maine coon cat was referred with uncontrolled diabetes
      mellitus. The cat had a 2 mo history of weight loss and intermittent vomiting. An
      abdominal ultrasound identified the presence of a large cavity measuring a
      maximum of 4.6 cm in the pancreas that was filled with a homogeneous echogenic
      fluid. Cytological analysis and culture of the fluid obtained from the pancreatic
      mass indicated the presence of a bacterial abscess. The application of
      nonsurgical drainage and the administration of glargine insulin and antibiotics
      resolved the clinical signs. The size of the pancreatic abscess was reduced after
      5 mo, and the cat achieved diabetic remission and remained healthy at the time
      this report was prepared. This case report describes the successful treatment of
      a pancreatic bacterial abscess concurrent with diabetes mellitus in a Maine coon
      cat. 

PMID- 25955145
TI  - Chronic splenic torsion in two dogs.
AB  - A 5 yr old spayed female poodle (case 1) was presented with a 4 mo history of
      lethargy, inappetence, and nonregenerative anemia. A 5 yr old castrated male
      French bulldog (case 2) was presented with a 2 wk history of mild abdominal pain,
      dyschezia, and intermittent anorexia. Both dogs were diagnosed with chronic
      splenic torsion based on changes in splenic position, echogenicity, and/or
      echotexture identified on B-mode abdominal ultrasonography, as well as either
      decreased or absent splenic blood flow on color-flow Doppler ultrasonography.
      Both dogs underwent splenectomy and had full resolution of clinical signs.
      Presentation of chronic splenic torsion is variable, and clinical signs can be
      nonspecific. Abdominal ultrasound with Doppler evaluation is an important
      diagnostic step that can lead to appropriate surgical intervention and good long
      term prognosis. 

PMID- 25955146
TI  - Primary lumbar extradural hemangiosarcoma in a dog.
AB  - A 9 yr old castrated male golden retriever weighing 36 kg was presented for
      evaluation of progressive left pelvic limb paresis and fecal and urinary
      incontinence. MRI demonstrated an extradural, ovoid mass compressing the lumbar
      spinal cord. Surgical excision of the mass was performed. Histologically, the
      mass was consistent with hemangiosarcoma with no involvement of the adjacent
      vertebrae. The dog underwent a doxorubicin-based chemotherapy protocol with the
      addition of oral cyclophosphamide. After completion of chemotherapy, the dog was
      evaluated q 4 mo for restaging. Clinicopathological evidence of primary tumor
      recurrence or metastatic disease was not detected for 15 mo after initial
      diagnosis and treatment. To the authors' knowledge, this is the first report of a
      primary extradural hemangiosarcoma in the lumbar vertebral column in a dog. The
      clinical presentation, diagnosis, treatment, and outcome are also discussed. 

PMID- 25955147
TI  - The renal effects of NSAIDs in dogs.
AB  - The quality of life for dogs with osteoarthritis can often be improved with
      nonsteroidal anti-inflammatory drugs (NSAIDs); however, the number of adverse
      drug events associated with NSAID use reported to the Federal Drug Administration
      Center for Veterinary Medicine is higher than that for any other companion animal
      drug. Of those events, adverse renal reactions are the second most reported.
      NSAIDs produce pharmacologic effects via inhibition of cyclooxygenase (COX),
      which decreases production of prostanoids. Prostaglandins are synthesized by both
      the COX-1 and COX-2 enzymes in the healthy kidney and influence renal blood flow,
      glomerular filtration rate, renin release, and Na excretion. There are important
      species differences in the renal expression of COX-1 and COX-2. For example, dogs
      have higher basal levels of COX-2 expression in the kidney compared with humans.
      In addition, in dogs with chronic kidney disease, an increase in COX-2 expression
      occurs and synthesis of prostaglandins shifts to the COX-2 pathway. For those
      reasons, NSAIDs that target COX-2 may be expected to adversely affect renal
      function in dogs, especially dogs with chronic kidney disease. The purpose of
      this review was to evaluate the literature to report the renal effects of NSAIDs
      in dogs. 

PMID- 25955148
TI  - Microfabrication of Custom Collagen Structures Capable of Guiding Cell Morphology
      and Alignment.
AB  - The patterning of biological components into structural analogues of native
      tissues to simulate an environment for directing cell growth is one important
      strategy in biomaterials fabrication. It is widely accepted that chemical,
      mechanical, and topological cues from the extracellular matrix (ECM) provide
      important signals for guiding cells to exhibit characteristic polarity,
      orientation, and morphology. To fully understand the delicate relationship
      between cell behavior and ECM features, biomaterials fabrication requires
      improved techniques for tailoring nano/microstructured patterns from relevant
      biological building blocks rather than using nonbiological materials. Here we
      reveal a unique approach for the nano/microfabrication of custom patterned
      biomaterials using collagen as the sole building material. With this new
      fabrication technique, we further revealed that custom collagen patterns could
      direct the orientation and morphology of fibroblast growth as a function of
      vertex density and pattern spacing. Our findings suggest that this technique may
      be readily adopted for the free form fabrication of custom cell scaffolds purely
      from natural biological molecules including collagen, among other relevant ECM
      components. 

PMID- 25955150
TI  - Human Serum Versus Human Serum Albumin Supplementation in Human Islet
      Pretransplantation Culture: In Vitro and In Vivo Assessment.
AB  - There is conflicting evidence favoring both the use of human serum (HS) and of
      human serum albumin (HSA) in human islet culture. We evaluated the effects of HS
      versus HSA supplementation on 1) in vitro beta-cell viability and function and 2)
      in vivo islet graft revascularization, islet viability, beta-cell death, and
      metabolic outcome after transplantation. Islets isolated from 14 cadaveric organ
      donors were cultured for 3 days in CMRL 1066 medium supplemented with HS or HSA.
      After 3 days in culture, beta-cell apoptosis was lower in HS group (1.41 +/- 0.27
      vs. 2.38 +/- 0.39%, p = 0.029), and the recovery of islets was 77 +/- 11% and 54
      +/- 1% in HS- and HSA-cultured groups, respectively. Glucose-stimulated insulin
      secretion (GSIS) was higher in HS group (29.4, range 10.4-99.9, vs. 22.3, range
      8.7-70.6, p = 0.031). In vivo viability and revascularization was determined in
      HS- and HSA-cultured islets transplanted into the anterior chamber of the eye of
      Balb/c mice (n = 14), and beta-cell apoptosis in paraffin-embedded mouse eyes.
      Islet viability and beta-cell apoptosis were similar in both groups.
      Revascularization was observed in one graft (HS group) on day 10 after
      transplantation. Islet function was determined in streptozotocin (STZ)-diabetic
      nude mice (n = 33) transplanted with 2,000 IEQs cultured with HS or HSA that
      showed similar blood glucose levels and percentage of normoglycemic animals over
      time. In conclusion, human islets cultured in medium supplemented with HS showed
      higher survival in vitro, as well as islet viability and function. The higher in
      vitro survival increased the number of islets available for transplantation.
      However, the beneficial effect on viability and function did not translate into
      an improved metabolic evolution when a similar number of HSA- and HS-cultured
      islets was transplanted. 

PMID- 25955149
TI  - Evaluation of plant growth regulatory activity of furofuran lignan bearing a
      7,9':7',9-diepoxy structure using optically pure (+)- and (-)-enantiomers.
AB  - The plant growth regulatory activity of furofuran lignan (7,9':7',9
      diepoxylignan) was evaluated by employing optically pure synthesized (+)- and (-)
      enantiomers. (+)-Sesamin possessing a 3,4-methylenedioxy group on the aromatic
      rings and 7-aryl structure showed growth promotion activity against lettuce roots
      (EC50 = 0.50 mM); on the other hand, growth inhibitory activity was observed
      against lettuce shoots (EC50 = 0.38 mM). Against ryegrass shoots, (-)-sesamolin,
      which has 3,4-methylenedioxy groups on the aromatic rings and a 7-acetal
      structure, was effective in showing growth inhibitory activity (EC50 = 0.23 mM).
      Different activity levels were observed between (+)- and (-)-enantiomers. It was
      assumed that the 3,4-methylenedioxy group on the aromatic ring was more potent
      for the plant growth regulatory activity. 

PMID- 25955151
TI  - Establishing the Framework for Fabrication of a Bioartificial Heart.
AB  - There is a chronic shortage of donor hearts. The ability to fabricate complete
      bioartificial hearts (BAHs) may be an alternative solution. The current study
      describes a method to support the fabrication and culture of BAHs. Rat hearts
      were isolated and subjected to a detergent based decellularization protocol to
      remove all cellular components, leaving behind an intact extracellular matrix.
      Primary cardiac cells were isolated from neonatal rat hearts, and direct cell
      transplantation was used to populate the acellular scaffolds. Bioartificial
      hearts were maintained in a custom fabrication gravity fed perfusion culture
      system to support media delivery. The functional performance of BAHs was assessed
      based on left ventricle pressure and on electrocardiogram. Furthermore, BAHs were
      sectioned and stained for the whole heart cardiac tissue distribution and for
      cardiac molecules, such as alpha-actinin, cardiac troponin I, collagen type I,
      connexin 43, von Willebrand factor, and ki67. Bioartificial hearts replicated a
      partial subset of properties of natural rat hearts. The current study provided a
      method for fabrication of a BAH and revealed challenges toward BAH fabrication
      with functional performance metrics of natural mammalian hearts. 

PMID- 25955152
TI  - Opening of Aortic Valve During Exercise Is Key to Preventing Development of
      Aortic Insufficiency During Ventricular Assist Device Treatment.
AB  - Although we previously demonstrated that opening of the native aortic valve (AV)
      at rest prevents development of aortic insufficiency (AI) during continuous-flow
      (CF) left ventricular assist device (LVAD) support, the clinical impact of native
      AV opening during exercise remained unknown. We enrolled 37 patients with a
      closed native AV at rest 3 months after CF LVAD implantation and followed them
      from 2006 to 2014. Seven patients (19%) who achieved opening of the native AV
      during cardiopulmonary exercise testing at 3 months (opening AV group) had higher
      exercise tolerability and improved left ventricular contractility during exercise
      compared with those with a closed native AV (closed AV group) (p < 0.05 for all).
      The opening group experienced no AI at 6 months and had a higher readmission-free
      rate because of cardiovascular events compared with the closed group during the 2
      years study period (100% vs. 56%, p = 0.005). Among those with a closed AV, use
      of the centrifugal pump was a significant predictor of AI-free status (p < 0.05;
      odds ratio, 5.400). In conclusion, opening of the native AV during exercise and
      centrifugal pump use were key to preventing the development of AI. Aggressive
      cardiac rehabilitation may have a prophylactic impact on development of AI during
      CF LVAD treatment. 

PMID- 25955154
TI  - Facile Construction of Chloroquine Containing PLGA-Based pDNA Delivery System for
      Efficient Tumor and Pancreatitis Targeting in Vitro and in Vivo.
AB  - Chloroquine diphosphate (CQ) was ingeniously used to take place of phosphate salt
      in traditional calcium phosphate coprecipitation method for pDNA transfection.
      With multiple roles of CQ in the novel Ca-CQ-pDNA complex including pDNA
      compaction and assistance in lysosome escape, the transfection efficiency of the
      pDNA was significantly increased relative to the traditional method. CQ did not
      intercalate into the DNA double helix as free CQ did, which was probably ascribed
      to the prior mixing of the pDNA with high concentration of calcium chloride. In
      order to construct efficacious vector for in vivo gene delivery, Ca-CQ-pDNA-PLGA
      NPs was designed and prepared. With entrapment efficiency, particle size and pDNA
      integrity as screening conditions, the optimal prescription was obtained and CaPi
      pDNA-PLGA-NPs made with classic calcium phosphate coprecipitation method after
      optimization was also prepared as control to systematically study the role of CQ
      in the novel vector. Physical characters of the vectors were comprehensively
      studied using TEM, DSC, and XRD. The safety of the vector both in vitro and in
      vivo was evaluated using MTT, hemolysis test, and histological sections. The Ca
      CQ-pDNA-PLGA-NPs dramatically enhanced the gene tranfection efficiency in Human
      Embryonic kidney HEK293 cells compared with the CaPi-pDNA-PLGA-NPs and presented
      an increasing gene transfection for up 144 h. The relative fast release of the CQ
      compared with pDNA from the nanoparticles was responsive for the increased
      transfection. The Did-labeled-Ca-CQ-pDNA-PLGA-NPs exhibited excellent tumor
      targeting efficiency and sustained circulation time in CT26 mouse model. The Ca
      CQ-pDNA-PLGA-NP loaded with the plasmid pVITRO2 expressing mSurvivin-T34A protein
      gave 70% tumor inhibition rate, which was partially ascribed to CQ. The Ca-CQ
      pDNA-PLGA-NPs showed high targeting efficiency in C57 acute pancreatitis model.
      In all, the Ca-CQ-pDNA-PLGA-NP was a promising candidate for targeted gene
      delivery to both tumor and pancreatitis. 

PMID- 25955153
TI  - The important role of von Willebrand factor in platelet-derived FVIII gene
      therapy for murine hemophilia A in the presence of inhibitory antibodies.
AB  - BACKGROUND: Our previous studies have demonstrated that targeting FVIII
      expression to platelets results in FVIII storage together with von Willebrand
      factor (VWF) in platelet alpha-granules and that platelet-derived FVIII (2bF8)
      corrects the murine hemophilia A phenotype even in the presence of high-titer
      anti-FVIII inhibitory antibodies (inhibitors). OBJECTIVE: To explore how VWF has
      an impact on platelet gene therapy for hemophilia A with inhibitors. METHODS:
      2bF8 transgenic mice in the FVIII(-/-) background (2bF8(tg+/-) F8(-/-) ) with
      varying VWF phenotypes were used in this study. Animals were analyzed by VWF
      ELISA, FVIII activity assay, Bethesda assay and tail clip survival test. RESULTS:
      Only 18% of 2bF8(tg+/-) F8(-/-) VWF(-/-) animals, in which VWF was deficient,
      survived the tail clip challenge with inhibitor titers of 3-8000 BU mL(-1) . In
      contrast, 82% of 2bF8(tg+/-) F8(-/-) VWF(+/+) mice, which had normal VWF levels,
      survived tail clipping with inhibitor titers of 10-50,000 BU mL(-1) . All
      2bF8(tg+/-) F8(-/-) VWF(-/-) mice without inhibitors survived tail clipping and
      no VWF(-/-) F8(-/-) mice survived this challenge. Because VWF is synthesized by
      endothelial cells and megakaryocytes and is distributed in both plasma and
      platelets in peripheral blood, we further investigated the effect of each
      compartment of VWF on platelet-FVIII gene therapy for hemophilia A with
      inhibitors. In the presence of inhibitors, 42% of animals survived tail clipping
      in the group with plasma-VWF and 50% survived in the platelet-VWF group.
      CONCLUSION: VWF is essential for platelet gene therapy for hemophilia A with
      inhibitors. Both platelet-VWF and plasma-VWF are required for optimal platelet
      derived FVIII gene therapy for hemophilia A in the presence of inhibitors.

PMID- 25955155
TI  - pGlcNAc Nanofiber Treatment of Cutaneous Wounds Stimulate Increased Tensile
      Strength and Reduced Scarring via Activation of Akt1.
AB  - Treatment of cutaneous wounds with poly-N-acetyl-glucosamine containing
      nanofibers (pGlcNAc), a novel polysaccharide material derived from a marine
      diatom, results in increased wound closure, antibacterial activities and innate
      immune responses. We have shown that Akt1 plays a central role in the regulation
      of these activities. Here, we show that pGlcNAc treatment of cutaneous wounds
      results in a smaller scar that has increased tensile strength and elasticity.
      pGlcNAc treated wounds exhibit decreased collagen content, increased collagen
      organization and decreased myofibroblast content. A fibrin gel assay was used to
      assess the regulation of fibroblast alignment in vitro. In this assay, fibrin
      lattice is formed with two pins that provide focal points upon which the gel can
      exert force as the cells align from pole to pole. pGlcNAc stimulation of embedded
      fibroblasts results in cellular alignment as compared to untreated controls, by a
      process that is Akt1 dependent. We show that Akt1 is required in vivo for the
      pGlcNAc-induced increased tensile strength and elasticity. Taken together, our
      findings suggest that pGlcNAc nanofibers stimulate an Akt1 dependent pathway that
      results in the proper alignment of fibroblasts, decreased scarring, and increased
      tensile strength during cutaneous wound healing. 

PMID- 25955157
TI  - Correction: miR-1915 and miR-1225-5p Regulate the Expression of CD133, PAX2 and
      TLR2 in Adult Renal Progenitor Cells.

PMID- 25955156
TI  - Understanding Voltage Gating of Providencia stuartii Porins at Atomic Level.
AB  - Bacterial porins are water-filled beta-barrel channels that allow translocation
      of solutes across the outer membrane. They feature a constriction zone,
      contributed by the plunging of extracellular loop 3 (L3) into the channel lumen.
      Porins are generally in the open state, but undergo gating in response to
      external voltages. To date the underlying mechanism is unclear. Here we report
      results from molecular dynamics simulations on the two porins of Providenica
      stuartii, Omp-Pst1 and Omp-Pst2, which display distinct voltage sensitivities.
      Voltage gating was observed in Omp-Pst2, where the binding of cations in-between
      L3 and the barrel wall results in exposing a conserved aromatic residue in the
      channel lumen, thereby halting ion permeation. Comparison of Omp-Pst1 and Omp
      Pst2 structures and trajectories suggests that their sensitivity to voltage is
      encoded in the hydrogen-bonding network anchoring L3 onto the barrel wall, as we
      observed that it is the strength of this network that governs the probability of
      cations binding behind L3. That Omp-Pst2 gating is observed only when ions flow
      against the electrostatic potential gradient of the channel furthermore suggests
      a possible role for this porin in the regulation of charge distribution across
      the outer membrane and bacterial homeostasis. 

PMID- 25955158
TI  - Dynamics of Circulating gammadelta T Cell Activity in an Immunocompetent Mouse
      Model of High-Grade Glioma.
AB  - Human gammadelta T cells are potent effectors against glioma cell lines in vitro
      and in human/mouse xenograft models of glioblastoma, however, this effect has not
      been investigated in an immunocompetent mouse model. In this report, we
      established GL261 intracranial gliomas in syngeneic WT C57BL/6 mice and measured
      circulating gammadelta T cell count, phenotype, Vgamma/Vdelta repertoire, tumor
      histopathology, NKG2D ligands expression, and T cell invasion at day 10-12 post
      injection and at end stage. Circulating gammadelta T cells transiently increased
      and upregulated Annexin V expression at post-tumor day 10-12 followed by a
      dramatic decline in gammadelta T cell count at end stage. T cell receptor
      repertoire showed no changes in Vgamma1, Vgamma4, Vgamma7 or Vdelta1 subsets from
      controls at post-tumor day 10-12 or at end stage except for an end-stage increase
      in the Vdelta4 population. Approximately 12% of gammadelta T cells produced IFN
      gamma. IL-17 and IL-4 producing gammadelta T cells were not detected. Tumor
      progression was the same in TCRdelta-/- C57BL/6 mice as that observed in WT mice,
      suggesting that gammadelta T cells exerted neither a regulatory nor a sustainable
      cytotoxic effect on the tumor. WT mice that received an intracranial injection of
      gammadelta T cells 15m following tumor placement showed evidence of local tumor
      growth inhibition but this was insufficient to confer a survival advantage over
      untreated controls. Taken together, our findings suggest that an early
      nonspecific proliferation of gammadelta T cells followed by their depletion
      occurs in mice implanted with syngeneic GL261 gliomas. The mechanism by which
      gammadelta T cell expansion occurs remains a subject for further investigation of
      the mechanisms responsible for this immune response in the setting of high-grade
      glioma. 

PMID- 25955159
TI  - AggLb Is the Largest Cell-Aggregation Factor from Lactobacillus paracasei Subsp.
      paracasei BGNJ1-64, Functions in Collagen Adhesion, and Pathogen Exclusion In
      Vitro.
AB  - Eleven Lactobacillus strains with strong aggregation abilities were selected from
      a laboratory collection. In two of the strains, genes associated with aggregation
      capability were plasmid located and found to strongly correlate with collagen
      binding. The gene encoding the auto-aggregation-promoting protein (AggLb) of
      Lactobacillus paracasei subsp. paracasei BGNJ1-64 was cloned using a novel, wide
      range-host shuttle cloning vector, pAZILSJ. The clone pALb35, containing a 11377
      bp DNA fragment, was selected from the SacI plasmid library for its ability to
      provide carriers with the aggregation phenotype. The complete fragment was
      sequenced and four potential ORFs were detected, including the aggLb gene and
      three surrounding transposase genes. AggLb is the largest known cell-surface
      protein in lactobacilli, consisting of 2998 aa (318,611 Da). AggLb belongs to the
      collagen-binding superfamily and its C-terminal region contains 20 successive
      repeats that are identical even at the nucleotide level. Deletion of aggLb causes
      a loss of the capacity to form cell aggregates, whereas overexpression increases
      cellular aggregation, hydrophobicity and collagen-binding potential. PCR
      screening performed with three sets of primers based on the aggLb gene of BGNJ1
      64 enabled detection of the same type of aggLb gene in five of eleven selected
      aggregation-positive Lactobacillus strains. Heterologous expression of aggLb
      confirmed the crucial role of the AggLb protein in cell aggregation and specific
      collagen binding, indicating that AggLb has a useful probiotic function in
      effective colonization of host tissue and prevention of pathogen colonization. 

PMID- 25955160
TI  - Do Parents Meet Adolescents' Monitoring Standards? Examination of the Impact on
      Teen Risk Disclosure and Behaviors if They Don't.
AB  - In this study, we examined how adolescents compare monitoring efforts by their
      parents to those of a "good parent" standard and assessed the impact of these
      comparisons on adolescent self-disclosure and risk behavior and their perceptions
      of their parents' monitoring knowledge. Survey responses from 519 adolescents (12
      17 years) at baseline of a larger, longitudinal study examining parental
      monitoring and adolescent risk were examined. Adolescents' "good parent
      comparisons" differed greatly by monitoring areas (e.g., telephone use, health,
      money); however, between 5.5% and 25.8% of adolescents believed their parents
      needed to monitor their activities more than they currently were monitoring.
      Alternatively, between 8.5% and 23.8% of adolescents believed their parents
      needed to monitor their activities less often. These perceptions significantly
      distinguished adolescents in terms of their level of disclosure, perceived
      monitoring knowledge, and risk involvement. Adolescents who viewed their parents
      as needing to monitor more were less likely to disclose information to their
      parents (p<.001), less likely to perceive their parents as having greater
      monitoring knowledge (p<.001), and more likely to be involved in a risk behaviors
      (p<.001) than adolescents who perceived their parents needed no change.
      Adolescent disclosure to a parent is a powerful predictor of adolescent risk and
      poor health outcomes. These findings demonstrate that adolescents' comparisons of
      their parents' monitoring efforts can predict differences in adolescent
      disclosure and future risk. Obtaining adolescent "good parent" comparisons may
      successfully identify intervention opportunities with the adolescent and parent
      by noting the areas of need and direction of monitoring improvement. 

PMID- 25955161
TI  - Priority setting for resources to improve the understanding of information about
      claims of treatment effects in the mass media.
AB  - OBJECTIVE: Claims about benefits and harms of treatments are common in the media.
      We engaged health journalists in prioritizing concepts of evidence-based medicine
      that we believe the public needs to understand to be able to assess claims about
      treatment effects; and which could improve how journalists report such
      information. METHODS: We conducted a three-day workshop with a group of Ugandan
      journalists in which we presented and explained the concepts. We asked
      journalists to prioritize groups of related concepts using four pre-specified
      criteria i.e. relevance of the concepts to journalists and their audiences; ease
      of comprehension; feasibility of developing resources for teaching the concepts
      and, whether such resources would potentially have an impact. Using a modified
      Delphi technique, participants ranked each group of concepts using these criteria
      on a scale of one to six (one = lowest; 6 = highest). We analyzed the rankings in
      real time using STATA statistical software. RESULTS: All six groups of concepts
      were considered relevant and comprehensible with scores of five and six on a
      scale of one to six. Twenty two out of 25 participants reported having understood
      the concepts well, with subjective scores of above 75 on a scale of one to 100.
      CONCLUSION: Journalists in Uganda recognize the importance of evidence-based
      medicine concepts in assessing claims about benefits and harms of treatments to
      them and their audiences. They should be empowered to use these and similar
      concepts in order to improve how information about effects of treatments is
      relayed in the media.

PMID- 25955162
TI  - Paradoxical Interaction between Ocular Activity, Perception, and Decision
      Confidence at the Threshold of Vision.
AB  - In humans and some other species perceptual decision-making is complemented by
      the ability to make confidence judgements about the certainty of sensory
      evidence. While both forms of decision process have been studied empirically, the
      precise relationship between them remains poorly understood. We performed an
      experiment that combined a perceptual decision-making task (identifying the
      category of a faint visual stimulus) with a confidence-judgement task (wagering
      on the accuracy of each perceptual decision). The visual stimulation paradigm
      required steady fixation, so we used eye-tracking to control for stray eye
      movements. Our data analyses revealed an unexpected and counterintuitive
      interaction between the steadiness of fixation (prior to and during stimulation),
      perceptual decision making, and post-decision wagering: greater variability in
      gaze direction during fixation was associated with significantly increased visual
      perceptual sensitivity, but significantly decreased reliability of confidence
      judgements. The latter effect could not be explained by a simple change in
      overall confidence (i.e. a criterion artifact), but rather was tied to a change
      in the degree to which high wagers predicted correct decisions (i.e. the
      sensitivity of the confidence judgement). We found no evidence of a differential
      change in pupil diameter that could account for the effect and thus our results
      are consistent with fixational eye movements being the relevant covariate.
      However, we note that small changes in pupil diameter can sometimes cause
      artefactual fluctuations in measured gaze direction and this possibility could
      not be fully ruled out. In either case, our results suggest that perceptual
      decisions and confidence judgements can be processed independently and point
      toward a new avenue of research into the relationship between them. 

PMID- 25955163
TI  - Care needs and clinical outcomes of older people with dementia: a population
      based propensity score-matched cohort study.
AB  - OBJECTIVE: To explore the healthcare resource utilization, psychotropic drug use
      and mortality of older people with dementia. DESIGN: A nationwide propensity
      score-matched cohort study. SETTING: National Health Insurance Research database.
      PARTICIPANTS: A total of 32,649 elderly people with dementia and their propensity
      score matched controls (n=32,649). MEASUREMENTS: Outpatient visits, inpatient
      care, psychotropic drug use, in-hospital mortality and all-cause mortality at 90
      and 365 days. RESULTS: Compared to the non-dementia group, a higher proportion of
      patients with dementia used inpatient services (1 year after index date: 20.91%
      vs. 9.55%), and the dementia group had more outpatient visits (median [standard
      deviation]: 7.00 [8.87] vs. 3.00 [8.30]). Furthermore, dementia cases with acute
      admission had the highest psychotropic drug utilization both at baseline and at
      the post-index dates (difference-in-differences: all <0.001). Dementia was
      associated with an increased risk of all-cause mortality (90 days, Odds ratio
      (OR)=1.85 [95%CI 1.67-2.05], p<0.001; 365 days, OR=1.59 [1.50-1.69], p<0.001) and
      in-hospital mortality (90 days, OR=1.97 [1.71-2.27], p<0.001; 365 days, OR=1.82
      [1.61-2.05], p<0.001) compared to matched controls. CONCLUSIONS: When older
      people with dementia are admitted for acute illnesses, they may increase their
      use of psychotropic agents and their risk of death, particularly in-hospital
      mortality.

PMID- 25955164
TI  - A Role of Myocardin Related Transcription Factor-A (MRTF-A) in Scleroderma
      Related Fibrosis.
AB  - In scleroderma (systemic sclerosis, SSc), persistent activation of myofibroblast
      leads to severe skin and organ fibrosis resistant to therapy. Increased
      mechanical stiffness in the involved fibrotic tissues is a hallmark clinical
      feature and a cause of disabling symptoms. Myocardin Related Transcription Factor
      A (MRTF-A) is a transcriptional co-activator that is sequestered in the cytoplasm
      and translocates to the nucleus under mechanical stress or growth factor
      stimulation. Our objective was to determine if MRTF-A is activated in the disease
      microenvironment to produce more extracellular matrix in progressive SSc.
      Immunohistochemistry studies demonstrate that nuclear translocation of MRTF-A in
      scleroderma tissues occurs in keratinocytes, endothelial cells, infiltrating
      inflammatory cells, and dermal fibroblasts, consistent with enhanced signaling in
      multiple cell lineages exposed to the stiff extracellular matrix. Inhibition of
      MRTF-A nuclear translocation or knockdown of MRTF-A synthesis abolishes the SSc
      myofibroblast enhanced basal contractility and synthesis of type I collagen and
      inhibits the matricellular profibrotic protein, connective tissue growth factor
      (CCN2/CTGF). In MRTF-A null mice, basal skin and lung stiffness was abnormally
      reduced and associated with altered fibrillar collagen. MRTF-A has a role in SSc
      fibrosis acting as a central regulator linking mechanical cues to adverse
      remodeling of the extracellular matrix. 

PMID- 25955166
TI  - A new report of FVII-inhibitor in a patient suffering from severe congenital FVII
      deficiency.

PMID- 25955167
TI  - Radiographic Assessment of Shoulder Position in 619 Idiopathic Scoliosis
      Patients: Can T1 Tilt Be Used as an Intraoperative Proxy to Determine
      Postoperative Shoulder Balance?
AB  - BACKGROUND: The purpose of this study is to assess radiographic shoulder measures
      from the preoperative to the postoperative time period, specifically to determine
      whether T1 tilt could be used as an intraoperative proxy for shoulder balance
      determination. This study focused on radiographic shoulder measures of 619
      adolescent idiopathic scoliosis patients who underwent spinal deformity surgery.
      METHODS: A prospective, multicenter database of adolescent idiopathic scoliosis
      was queried to identify all patients who had undergone spinal deformity surgery
      with >2 years of follow-up postoperatively. Radiographic analysis focused on
      measures of shoulder balance: T1 tilt, clavicle angle, and radiographic shoulder
      height. RESULTS: A total of 619 patients were included in this analysis. Mean age
      at surgery was 14.8 years with 83% female. Mean preoperative curve size was 58.0
      degrees. Mean T1 tilt preoperatively was -0.10 degrees and postoperatively 2.42
      degrees. Mean clavicle angle preoperatively was -1.39 degrees and postoperatively
      0.79 degrees. Mean radiographic shoulder height preoperatively was -7.04 mm and
      postoperatively 1.63 mm. All 3 radiographic parameters demonstrated reasonable
      correlation preoperatively and postoperatively to each other. To assess the
      viability of T1 tilt as an intraoperative proxy for shoulder balance,
      standardized ratios between the variables were created. Analysis of these ratios
      demonstrated little or no relationship preoperatively to postoperatively, hence
      the relationship of T1 tilt to radiographic shoulder height does not remain
      constant. CONCLUSIONS: Analysis of the relationship of T1 tilt to radiographic
      shoulder height from preoperative to postoperative did not demonstrate
      consistency. Lenke 3 and 6 curve patterns demonstrated preoperative to
      postoperative correlation, both with nonstructural proximal thoracic curves;
      however, for the remaining curve patterns T1 tilt cannot be used as an
      intraoperative proxy for shoulder balance. LEVEL OF EVIDENCE: Level IV.

PMID- 25955165
TI  - An Extended Surface Loop on Toxoplasma gondii Apical Membrane Antigen 1 (AMA1)
      Governs Ligand Binding Selectivity.
AB  - Apicomplexan parasites are the causative agents of globally prevalent diseases
      including malaria and toxoplasmosis. These obligate intracellular pathogens have
      evolved a sophisticated host cell invasion strategy that relies on a parasite
      host cell junction anchored by interactions between apical membrane antigens
      (AMAs) on the parasite surface and rhoptry neck 2 (RON2) proteins discharged from
      the parasite and embedded in the host cell membrane. Key to formation of the AMA1
      RON2 complex is displacement of an extended surface loop on AMA1 called the DII
      loop. While conformational flexibility of the DII loop is required to expose the
      mature RON2 binding groove, a definitive role of this substructure has not been
      elucidated. To establish a role of the DII loop in Toxoplasma gondii AMA1, we
      engineered a form of the protein where the mobile portion of the loop was
      replaced with a short Gly-Ser linker (TgAMA1DeltaDIIloop). Isothermal titration
      calorimetry measurements with a panel of RON2 peptides revealed an influential
      role for the DII loop in governing selectivity. Most notably, an Eimeria tenella
      RON2 (EtRON2) peptide that showed only weak binding to TgAMA1 bound with high
      affinity to TgAMA1DeltaDIIloop. To define the molecular basis for the
      differential binding, we determined the crystal structure of TgAMA1DeltaDIIloop
      in complex with the EtRON2 peptide. When analyzed in the context of existing AMA1
      RON2 structures, spatially distinct anchor points in the AMA1 groove were
      identified that, when engaged, appear to provide the necessary traction to
      outcompete the DII loop. Collectively, these data support a model where the AMA1
      DII loop serves as a structural gatekeeper to selectively filter out ligands
      otherwise capable of binding with high affinity in the AMA1 apical groove. These
      data also highlight the importance of considering the functional implications of
      the DII loop in the ongoing development of therapeutic intervention strategies
      targeting the AMA1-RON2 invasion complex. 

PMID- 25955168
TI  - Biomechanics of Slipped Capital Femoral Epiphysis: Evaluation of the Posterior
      Sloping Angle.
AB  - BACKGROUND: The posterior sloping angle (PSA) has been shown to be an objective
      and reproducible predictor of the risk of patients developing contralateral
      slipped capital femoral epiphysis (SCFE); however, prophylactic fixation remains
      controversial. This in vitro study investigates the biomechanical basis of using
      a 15-degree PSA as a threshold for prophylactic fixation. METHODS: Synthetic bone
      in vitro models of the proximal femur were constructed with a PSA of 10 degrees
      as a control (normal) group (n=6) by performing an osteotomy at the physis and
      gluing the head back onto the neck. SCFE groups were created with a PSA of 15,
      20, 25, 30, 50, or 60 degrees, by excising a wedge from the posterior neck and
      gluing them back at the new angle with corresponding posterior translation
      proportional to the slip angle, and loaded superoinferiorly in compression, to
      failure. Ultimate strength, energy to failure, and stiffness were recorded.
      RESULTS: Increasing the PSA from 10 to 15 degrees only reduced ultimate strength
      by 13% (P>0.05; CI, -0.21 to -0.06), though a significantly lesser energy to
      failure was required (-58%, P<0.05; CI, -0.68 to -0.48). Increasing the angle to
      20 degrees resulted in a further significant decrease in strength (-19%, P<0.05;
      CI, -0.28 to -0.10) and energy to failure (-45%, P<0.05; CI, -0.53 to -0.84). The
      severe SCFE (60-degree PSA) was significantly weaker and less rigid that the
      control, and the mild and moderate SCFE models (P<0.01). CONCLUSIONS: These
      biomechanical data support the threshold of 15-degree PSA as an objective measure
      for prophylactic fixation of the contralateral hip in SCFE. CLINICAL RELEVANCE:
      The number needed to treat with (minimally invasive) prophylactic fixation to
      prevent contralateral SCFE can be minimized if the above-mentioned threshold is
      used.

PMID- 25955169
TI  - Evaluating Length: The Use of Low-dose Biplanar Radiography (EOS) and Tantalum
      Bead Implantation.
AB  - BACKGROUND: Low-dose biplanar radiography (EOS) is an appealing imaging modality
      for use in children given its low radiation and ease of use. The goal of this
      study was to determine the accuracy and reliability of EOS compared with CT
      scanogram for measurement of leg length and to assess interrater and intrarater
      reliability of measured interbead distances for EOS and CT scanogram after
      insertion of tantalum beads into lamb femurs. METHODS: Tantalum beads (0.8 mm)
      were inserted into the cortex on both the medial and lateral sides of 10
      skeletally immature lamb femurs. CT scanogram and EOS imaging were obtained.
      Measurements of total length and distance between bead pairs were recorded on
      anteroposterior and lateral views by 2 orthopaedic surgeons on 2 separate
      occasions. Pearson correlations were performed for statistical comparisons.
      RESULTS: EOS measurements showed near-perfect correlation to those of CT
      scanogram (r>0.96, P<0.001). Intrarater reliability was excellent for all
      measurements with EOS (r>0.98, P<0.001) and CT scanogram (r>0.99, P<0.001) as was
      interrater reliability for EOS (r>0.98, P<0.001) and CT scanogram (r>0.99,
      P<0.001). CONCLUSIONS: EOS is comparable with CT scanogram in the assessment of
      limb length and the distance between 2 radiopaque markers. Reliability was
      excellent for all measurements. The combination of EOS imaging and tantalum bead
      implantation may be an effective way to evaluate physeal growth following
      procedures such as epiphysiodesis and physeal bar resection. LEVEL OF EVIDENCE:
      Level II-diagnostic

PMID- 25955170
TI  - Ventriculoperitoneal Shunt Fracture Following Application of Halo-Gravity
      Traction: A Case Report.
AB  - BACKGROUND: Ventriculoperitoneal (VP) shunt malfunctions are very common, and
      shunt fracture is one of the most common causes. Shunt fractures are often a
      result of calcification and tethering, which predispose the tubing to fracture
      when mechanical stresses are applied. This case report describes a case of shunt
      fracture following application of halo-gravity traction for correction of spinal
      deformity. METHODS: Chart and imaging data for a single case were reviewed and
      reported in this retrospective case study. RESULTS: A 10-year-old female, being
      treated for syndromic scoliosis, underwent posterior surgical release and
      application of halo-gravity traction. Increasing weight of traction was applied
      over a period of 6 weeks, for gradual deformity correction. It was noted on the 6
      week cervical spine radiograph that the VP shunt had fractured at the base of the
      neck. The patient was taken to the operating room and intraoperative findings
      confirmed shunt fracture. This was repaired without complications. CONCLUSIONS:
      This case, to our best knowledge, is the first reported occurrence of shunt
      fracture following application of halo-gravity traction. It demonstrates the
      importance of careful monitoring of patients with VP shunts, when they are
      undergoing traction for correction of spinal deformity. LEVEL OF EVIDENCE: Level
      IV.

PMID- 25955171
TI  - Rib Fractures in Osteogenesis Imperfecta: Have we Learnt Anything About Child
      Abuse?

PMID- 25955172
TI  - Efficacy of 2 Regional Pain Control Techniques in Pediatric Foot Surgery.
AB  - BACKGROUND: Peripheral nerve blocks (PNBs) have the potential to reduce
      postoperative pain. The use of ultrasound (US) to guide PNBs may be more
      beneficial than nerve stimulation (NS); however, very few studies have studied
      this technique in children. The objective of this study was to compare
      postoperative pain control in pediatric patients who had general anesthesia (GA)
      alone compared with those who had PNB performed by NS, or PNB with both NS and US
      guidance. Our hypothesis was that compared with NS, the US-guided PNB would
      result in reduced postoperative pain and opioid use, and that both PNB conditions
      would have improved outcomes compared with GA. METHODS: A retrospective chart
      review of foot and ankle surgery included 103 patients who were stratified into 3
      groups: GA, PNB with NS, and PNB with NS and US. Pain levels were measured with
      visual pain scales at 2, 4, 6, 8, 12, and 24 hours postoperatively. Days of
      hospitalization, morphine and oxycodone use by weight, and time to first PRN
      opioid use were also recorded. A repeated measure analysis of variance was used
      to compare the groups, and the proportion of patients who reported a visual
      analog scale score of 0 was calculated for each time point. RESULTS: There were
      no significant differences in pain levels between groups for the first 12 hours,
      but the US group had higher pain levels at 24 hours. Both US and NS groups had a
      longer time to PRN opioid use and used significantly less morphine compared with
      GA. The US group had a significantly greater proportion of pain-free patients
      than the other 2 groups for the first 6 hours. CONCLUSIONS: The use of US
      guidance is beneficial in postoperative pain control. Both US-guided and NS
      guided PNB are preferable to GA alone for lower extremity orthopaedic surgery in
      the pediatric population. LEVEL OF EVIDENCE: III, retrospective comparative
      study.

PMID- 25955173
TI  - Comparison Between Buddy Taping With a Short-Arm Splint and Operative Treatment
      for Phalangeal Neck Fractures in Children.
AB  - BACKGROUND: Phalangeal neck fractures in children are difficult to treat
      conservatively because of the difficulty in maintaining reduction, obtaining
      satisfactory follow-up x-rays, and the limited remodeling potential. The purpose
      of this study was to present the results after using buddy taping with a short
      arm splint for phalangeal neck fracture in children and to compare with operative
      treatment. METHODS: Thirty-seven patients below 12 years old who had phalangeal
      neck fractures were included. Nineteen patients were underwent conservative
      treatment and 18 patients were underwent operative fixation with Kirschner wires.
      Clinical outcome and radiographs between groups were compared. RESULTS: There
      were no significant differences between conservative group and operative group in
      the sagittal angulation, coronal angulation, and translation at immediately after
      reduction, at the 6-week, and final follow-up examination. CONCLUSION: Buddy
      taping with a short-arm splint for treating phalangeal neck fractures had
      acceptable outcomes compared to that with surgical correction.

PMID- 25955174
TI  - Does Clubfoot Treatment Need to Begin As Soon As Possible?
AB  - INTRODUCTION: Parents of an infant with an idiopathic clubfoot deformity are
      often urged by their primary care physician to seek treatment as soon as
      possible. This advice frequently appears in many general pediatric and pediatric
      orthopaedic textbooks and monographs on the subject. This recommendation has not
      changed since the wide acceptance of the minimally invasive Ponseti method to
      treat clubfoot. We determined the correlations among patient-related variables,
      early treatment variables, and the age at which the patient was first seen to
      begin treatment. METHODS: Infants with moderate to very severe idiopathic
      clubfoot deformity were invited to participate. Age at which the patient
      presented to begin treatment was correlated against early treatment-related
      variables, including number of casts required, cast slippage, cast-related skin
      problems, brace-related skin problems, early noncompliance with brace wearing,
      and relapse before 1 year. Patient-related variables were also correlated against
      age at first visit. RESULTS: Over 7 years, 176 infants met the inclusion
      criteria. There were no significant differences in the aspects of the early
      management as a function of age at first visit, with the exception of cast
      slippage (P=0.05). CONCLUSIONS: The age at first visit influenced the incidence
      of cast slippage, but otherwise did not affect the early treatment of clubfoot.
      CLINICAL RELEVANCE: The treatment of idiopathic clubfoot deformity should not be
      considered an orthopaedic emergency, and parents whose infants are born with this
      deformity should be counseled accordingly.

PMID- 25955175
TI  - Maximum entropy, word-frequency, Chinese characters, and multiple meanings.
AB  - The word-frequency distribution of a text written by an author is well accounted
      for by a maximum entropy distribution, the RGF (random group formation)
      prediction. The RGF-distribution is completely determined by the a priori values
      of the total number of words in the text (M), the number of distinct words (N)
      and the number of repetitions of the most common word (k(max)). It is here shown
      that this maximum entropy prediction also describes a text written in Chinese
      characters. In particular it is shown that although the same Chinese text written
      in words and Chinese characters have quite differently shaped distributions, they
      are nevertheless both well predicted by their respective three a priori
      characteristic values. It is pointed out that this is analogous to the change in
      the shape of the distribution when translating a given text to another language.
      Another consequence of the RGF-prediction is that taking a part of a long text
      will change the input parameters (M, N, k(max)) and consequently also the shape
      of the frequency distribution. This is explicitly confirmed for texts written in
      Chinese characters. Since the RGF-prediction has no system-specific information
      beyond the three a priori values (M, N, k(max)), any specific language
      characteristic has to be sought in systematic deviations from the RGF-prediction
      and the measured frequencies. One such systematic deviation is identified and,
      through a statistical information theoretical argument and an extended RGF-model,
      it is proposed that this deviation is caused by multiple meanings of Chinese
      characters. The effect is stronger for Chinese characters than for Chinese words.
      The relation between Zipf's law, the Simon-model for texts and the present
      results are discussed.

PMID- 25955176
TI  - Polymorphic variants in the dopamine receptor D2 in women with endometriosis
      related infertility.
AB  - Data suggests that dopamine receptor DRD2 gene variants may contribute to
      hyperprolactinemia and that they may be risk factors for endometriosis-related
      infertility. The purpose of the present study was to determine whether nucleotide
      variants of the DRD2 gene may be associated with infertility related to
      endometriosis. Five DRD2 SNPs, rs1800497, rs6277, rs2283265, rs4245146 and
      rs4648317, which are located in different blocks of linkage disequilibrium, were
      studied in 151 cases and 381 controls. No significant differences between DRD2
      rs1800497, rs6277, rs2283265, rs4245146 and rs4648317 genotype, allele nor
      haplotype frequencies were observed in women with endometriosis-related
      infertility compared with the control group. The present results did not confirm
      DRD2 gene variants to be genetic risk factors for endometriosis-related
      infertility.

PMID- 25955177
TI  - Identifying the Deleterious Effect of Rare LHX4 Allelic Variants, a Challenging
      Issue.
AB  - LHX4 is a LIM homeodomain transcription factor involved in the early steps of
      pituitary ontogenesis. To date, 8 heterozygous LHX4 mutations have been reported
      as responsible of combined pituitary hormone deficiency (CPHD) in Humans. We
      identified 4 new LHX4 heterozygous allelic variants in patients with congenital
      hypopituitarism: W204X, delK242, N271S and Q346R. Our objective was to determine
      the role of LHX4 variants in patients' phenotypes. Heterologous HEK293T cells
      were transfected with plasmids encoding for wild-type or mutant LHX4. Protein
      expression was analysed by Western Blot, and DNA binding by electro-mobility
      shift assay experiments. Target promoters of LHX4 were cotransfected with wild
      type or mutant LHX4 to test the transactivating abilities of each variant. Our
      results show that the W204X mutation was associated with early GH and TSH
      deficiencies and later onset ACTH deficiency. It led to a truncated protein
      unable to bind to alpha-Gsu promoter binding consensus sequence. W204X was not
      able to activate target promoters in vitro. Cotransfection experiments did not
      favour a dominant negative effect. In contrast, all other mutants were able to
      bind the promoters and led to an activation similar as that observed with wild
      type LHX4, suggesting that they were likely polymorphisms. To conclude, our study
      underlines the need for functional in vitro studies to ascertain the role of rare
      allelic variants of LHX4 in disease phenotypes. It supports the causative role of
      the W204X mutation in CPHD and adds up childhood onset ACTH deficiency to the
      clinical spectrum of the various phenotypes related to LHX4 mutations. 

PMID- 25955178
TI  - Views of Swedish commissioning parents relating to the exploitation discourse in
      using transnational surrogacy.
AB  - Transnational surrogacy, when people travel abroad for reproduction with the help
      of a surrogate mother, is a heavily debated phenomenon. One of the most salient
      discourses on surrogacy is the one affirming that Westerners, in their quest for
      having a child, exploit poor women in countries such as India. As surrogacy
      within the Swedish health care system is not permitted, Swedish commissioning
      parents have used transnational surrogacy, and the majority has turned to India.
      This interview study aimed to explore how commissioning parents negotiate the
      present discourses on surrogacy. Findings from the study suggest that the
      commissioning parents' views on using surrogacy are influenced by competing
      discourses on surrogacy represented by media and surrogacy agencies. The use of
      this reproductive method resulted, then, in some ambiguity. Although
      commissioning parents defy the exploitation discourse by referring to what they
      have learnt about the surrogate mother's life situation and by pointing at the
      significant benefits for her, they still had a request for regulation of
      surrogacy in Sweden, to better protect all parties involved. This study, then,
      gives a complex view on surrogacy, where the commissioning parents simultaneously
      argue against the exploitation discourse but at the same time are uncertain if
      the surrogate mothers are well protected in the surrogacy arrangements. Their
      responses to the situation endorse the need for regulation both in Sweden and
      India. 

PMID- 25955179
TI  - Hypoglycemic effects of aqueous persimmon leaf extract in a murine model of
      diabetes.
AB  - Previously, powdered persimmon leaves have been reported to have glucose- and
      lipid-lowering effects in diabetic (db/db) mice. As persimmon leaf is commonly
      consumed as tea, an aqueous extract of persimmon leaves (PLE) was prepared and
      its anti-diabetic efficacy was investigated. In the present study, PLE was tested
      for its inhibitory activity on alpha-glucosidase in vitro. An oral maltose
      tolerance test was performed in diabetic mice. Next, the acute effect of PLE was
      examined in streptozotocin-induced diabetic mice. Last, the long-term effect of
      PLE supplementation was assessed in db/db after eight weeks. An oral glucose
      tolerance test, biochemical parameters, as well as histological analyses of liver
      and pancreas were evaluated at the end of the study. PLE inhibited alpha
      glucosidase activity and increased antioxidant capacity. Streptozotocin-induced
      diabetic mice pre-treated with PLE displayed hypoglycemic activity. Daily oral
      supplementation with PLE for eight weeks reduced body weight gain without
      affecting food intake, enhanced the glucose tolerance during the oral glucose
      tolerance test (OGTT), improved blood lipid parameters, suppressed fat
      accumulation in the liver and maintained islet structure in db/db mice. Further
      mechanistic study showed that PLE protected pancreatic islets from glucotoxicity.
      In conclusion, the results of the present study indicated that PLE exhibits
      considerable anti-diabetic effects through alpha-glucosidase inhibition and
      through the maintenance of functional beta-cells. These results provided a
      rationale for the use of persimmon leaf tea for the maintenance of normal blood
      glucose levels in diabetic patients.

PMID- 25955181
TI  - Body ownership: When feeling and knowing diverge.
AB  - Individuals with the peculiar disturbance of 'overcompleteness' experience an
      intense desire to amputate one of their healthy limbs, describing a sense of
      disownership for it (Body Integrity Identity Disorder - BIID). This condition is
      similar to somatoparaphrenia, the acquired delusion that one's own limb belongs
      to someone else. In ten individuals with BIID, we measured skin conductance
      response to noxious stimuli, delivered to the accepted and non-accepted limb,
      touching the body part or simulating the contact (stimuli approach the body
      without contacting it), hypothesizing that these individuals have responses like
      somatoparaphrenic patients, who previously showed reduced pain anticipation, when
      the threat was directed to the disowned limb. We found reduced anticipatory
      response to stimuli approaching, but not contacting, the unwanted limb.
      Conversely, stimuli contacting the non-accepted body-part, induced stronger SCR
      than those contacting the healthy parts, suggesting that feeling of ownership is
      critically related to a proper processing of incoming threats. 

PMID- 25955180
TI  - Targeted Disruption of ALK Reveals a Potential Role in Hypogonadotropic
      Hypogonadism.
AB  - Mice lacking ALK activity have previously been reported to exhibit subtle
      behavioral phenotypes. In this study of ALK of loss of function mice we present
      data supporting a role for ALK in hypogonadotropic hypogonadism in male mice. We
      observed lower level of serum testosterone at P40 in ALK knock-out males,
      accompanied by mild disorganization of seminiferous tubules exhibiting decreased
      numbers of GATA4 expressing cells. These observations highlight a role for ALK in
      testis function and are further supported by experiments in which chemical
      inhibition of ALK activity with the ALK TKI crizotinib was employed. Oral
      administration of crizotinib resulted in a decrease of serum testosterone levels
      in adult wild type male mice, which reverted to normal levels after cessation of
      treatment. Analysis of GnRH expression in neurons of the hypothalamus revealed a
      significant decrease in the number of GnRH positive neurons in ALK knock-out mice
      at P40 when compared with control littermates. Thus, ALK appears to be involved
      in hypogonadotropic hypogonadism by regulating the timing of pubertal onset and
      testis function at the upper levels of the hypothalamic-pituitary gonadal axis. 

PMID- 25955182
TI  - The mental and subjective skin: Emotion, empathy, feelings and thermography.
AB  - We applied thermography to investigate the cognitive neuropsychology of emotions,
      using it as a somatic marker of subjective experience during emotional tasks. We
      obtained results that showed significant correlations between changes in facial
      temperature and mental set. The main result was the change in the temperature of
      the nose, which tended to decrease with negative valence stimuli but to increase
      with positive emotions and arousal patterns. However, temperature change was
      identified not only in the nose, but also in the forehead, the oro-facial area,
      the cheeks and in the face taken as a whole. Nevertheless, thermic facial
      changes, mostly nasal temperature changes, correlated positively with
      participants' empathy scores and their performance. We found that temperature
      changes in the face may reveal maps of bodily sensations associated with
      different emotions and feelings like love. 

PMID- 25955185
TI  - Letters.

PMID- 25955183
TI  - Anti-oxidant effect of heme oxygenase-1 on cigarette smoke-induced vascular
      injury.
AB  - Cigarette smoking, a major independent risk factor of atherosclerosis, can cause
      oxidative and inflammatory damage of vascular tissue. Heme oxygenase-1 (HO-1) is
      an endogenous cytoprotective enzyme with an anti-oxidant role in cells. The aim
      of the present study was to investigate whether HO-1 was able to protect vascular
      and endothelial cells from the oxidative damage induced by cigarette smoking. It
      was observed that cigarette smoking was able to induce the generation of the
      reactive oxygen species (ROS) in carotid arteries of rats. Hemin, a widely used
      HO-1 inducer, was able to reduce the generation of ROS. In addition, when human
      umbilical vein endothelial cells (HUVECs) were cultured in the serum of smoking
      rats, this was able to increase ROS, and the protective effect of hemin was also
      observed in this system. In conclusion, the present study demonstrated that
      cigarette smoking causes oxidative damage of vascular cells and HUVECs by
      inducing the generation of ROS, while HO-1 has an anti-oxidant effect in this
      course. This also implied that hemin, an inducer of HO-1, may have potential
      therapeutic applicability in the prevention of vascular diseases caused by
      cigarette smoking. 

PMID- 25955186
TI  - A Systematic Review of Lumbar Fusion Rates With and Without the Use of rhBMP-2.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: To evaluate literature comparing
      fusion rates in anterior lumbar interbody fusion (ALIF), posterior lumbar
      interbody/transforaminal lumbar interbody fusion (PLIF/TLIF), and posterolateral
      lumbar fusion (PLF) with and without recombinant human bone morphogenetic protein
      2 (rhBMP-2). SUMMARY OF BACKGROUND DATA: rhBMP-2 is used for the FDA-approved
      indication of single-level ALIF with LT-Cage and off-label for PLIF/TLIF, and
      PLF. Due to recent controversies, it is essential to evaluate the literature for
      its effects on fusion rates to evaluate whether benefits outweigh potential
      complications. METHODS: A Medline search was performed of clinical studies
      published between May 2000 and May 2012 comparing fusion rates after ALIF,
      PLIF/TLIF, and PLF surgery with versus without rhBMP-2. Only studies with a
      control arm were reviewed. RESULTS: 16 studies were reviewed (1794 patients, 995
      treated with rhBMP-2 and 799 without). 5 of 5 studies for PLIF/TLIF (including
      301 of 301 patients), 1 of 4 for ALIF (including 279 of 589 patients), and 3 of 7
      for PLF (including 272 of 904 patients) reported no significant improvement in
      fusion rates with rhBMP-2 compared with those without rhBMP-2 at longest follow
      up investigated. Average fusion rate 24 months after surgery was 97.8% for ALIF
      (n = 316), 95.7% for PLIF/TLIF (n = 141), and 93.6% for PLF (n = 422) with rhBMP
      2 and 88.2% (n = 228), 89.5% (n = 86), and 83.1% (n = 372) without rhBMP-2, for
      ALIF, PLIF/TLIF, and PLF, respectively. Odds ratio of fusion were calculated as
      7.08 (95% CI: 1.54-32.7) in ALIF, 1.98 (95% CI: 0.39-10.1) in PLIF/TLIF, and 3.06
      (95% CI: 1.61-5.80) in PLF with rhBMP-2 as compared with without rhBMP-2.
      CONCLUSION: Although numerous studies did not show statistically significant
      improvement in fusion rates with rhBMP-2 use, analysis of combined studies
      revealed significant improvement in fusion rate with rhBMP-2 in ALIF and PLF
      patients. Notably, even when pooling data from several studies, rhBMP-2 did not
      result in statistically significantly improved fusion rates in PLIF/TLIF.
      However, heterogeneity of rhBMP-2 dosing, surgical techniques, and quality of
      papers reviewed may limit the validity of conclusions drawn. LEVEL OF EVIDENCE:
      4.

PMID- 25955187
TI  - Even Worse - Risk Factors and Protective Factors for Transition from Chronic
      Localized Low Back Pain to Chronic Widespread Pain in General Practice: A Cohort
      Study.
AB  - STUDY DESIGN: Prospective cohort study with patients with chronic low back pain
      (CLBP) at primary care setting. OBJECTIVE: The aim of our study was to identify
      predictors for transition from localized CLBP to chronic widespread pain in
      general practice. In contrast to the typically investigated risk factors, this
      study also focuses intensively on protective factors, which decrease the
      probability of chronic widespread pain. For this, we investigated the resources
      resilience and coping strategies, which are suspected as potential protective
      factors for incident chronic pain syndromes. SUMMARY OF BACKGROUND DATA: In
      primary care, about a quarter of patients with CLBP experience chronic widespread
      pain (CWP). METHODS: Patients experiencing localized CLBP were included and
      evaluated after a 6- and 12-month follow-up period regarding the development of
      CWP. Potential risk factors (sociodemographic data, pain characteristics,
      depression, anxiety, somatization), protective factors (resilience, coping
      strategies), and sample characteristics were assessed at baseline. Predictor
      identification was done by multivariate logistic regression analysis. RESULTS:
      The 1-year incidence for the onset of CWP among patients with CLBP was 23.8%. We
      identified the 3 risk factors, female sex, long duration of back pain, and a high
      rate of psychosomatic symptoms, for the onset of CWP among patients with CLBP.
      Coping resources and resilience had no impact on the transition from CLBP to CWP.
      CONCLUSION: The results suggest that CWP is no independent entity but rather a
      particularly negative occurrence on a continuum of chronic pain. Processes of
      somatization play a major role in the development of this extreme. LEVEL OF
      EVIDENCE: 2.

PMID- 25955188
TI  - Primary Versus Revision Single-level Minimally Invasive Lumbar Discectomy:
      Analysis of Clinical Outcomes and Narcotic Utilization.
AB  - STUDY DESIGN: Retrospective cohort analysis of a prospectively maintained
      registry. OBJECTIVE: To compare the intraoperative variables, surgical outcomes,
      and narcotic utilization between primary and revision 1-level minimally invasive
      (MIS) lumbar discectomies. SUMMARY OF BACKGROUND DATA: Revision spine surgery may
      be associated with longer procedural time and greater soft tissue disruption. Few
      studies have analyzed the surgical outcomes and narcotic utilization associated
      with MIS revision lumbar discectomies. METHODS: A retrospective analysis of 227
      consecutive cases of MIS 1-level lumbar discectomy for degenerative spinal
      pathology between 2009 and 2014 by a single surgeon was performed. Patients were
      stratified into primary and revision cohorts. Demographics, comorbidity,
      intraoperative parameters, peri- and postoperative outcomes, and reoperations
      were assessed. Postoperative narcotic utilization was compared between cohorts.
      Statistical analyses were performed using Student t-test and Pearson chi test. A
      P < 0.05 denoted statistical significance. RESULTS: Of the 227 cases included,
      186 patients (81.9%) and 41 patients (18.1%) were included in the primary and
      revision cohorts, respectively. Demographics, comorbidity, smoking status,
      preoperative visual analogue scale (VAS) scores, and estimated blood loss did not
      differ between cohorts. However, the revision cohort demonstrated a longer
      procedural time, increased length of hospitalization, and higher postoperative
      narcotic utilization. Although not statistically significant, revision patients
      trended toward higher 6-week postoperative VAS scores and reherniation rates. In
      addition, revision patients were more likely to undergo subsequent lumbar fusion
      than primary patients. CONCLUSION: The findings suggest that revision MIS lumbar
      discectomy may be associated with increased procedural time, increased length of
      hospitalization, and increased postoperative narcotic utilization. Whereas
      revision patients trended toward higher postoperative VAS scores at 6 weeks, both
      cohorts demonstrated similar pain levels at final follow-up. Finally, revision
      patients may be at a greater risk of reherniation and subsequent reoperation.
      Further studies are warranted to characterize the independent risk factors for a
      revision lumbar discectomy. LEVEL OF EVIDENCE: 3.

PMID- 25955189
TI  - Specific Rehabilitation Protocol to Treat the Lumbar Stenosis.

PMID- 25955190
TI  - Patterns of radiotherapy practice for pancreatic cancer: Results of the
      Gastrointestinal Radiation Oncology Study Group multi-institutional survey.
AB  - No information is currently available regarding pancreatic cancer (PC) pattern of
      care in Italy. In the present study, a nationwide survey using a questionnaire
      was performed to enquire the local standards for PC diagnosis and radiotherapy
      treatment. Fifty-seven percent of 140 Italian centres completed questionnaire.
      The main causes of no radiotherapy indication were poor general condition (45%)
      and lack of guidelines (25%). Physicians (38%) employed neoadjuvant therapy in
      locally advanced PC patients, while in other centres (62%) adjuvant
      chemoradiation was administered. Adjuvant gemcitabine-based chemotherapy was
      selected as the treatment of choice by 59% of centres. Patients were treated
      mostly with doses of 50-54.9 Gy on the tumour (or bed) plus lymph nodes. A 3D-CRT
      technique was used in 81.2% of centres, while IMRT and IGRT were available in
      61.2 and 48.7% of cases, respectively. Extensive variation exists with regard to
      patterns of care for PC in Italy. Nevertheless, cooperative studies emerging from
      this survey appeared beneficial.

PMID- 25955191
TI  - A randomized controlled trial of the effects of vitamin D supplementation on
      arterial stiffness and aortic blood pressure in Native American women.
AB  - OBJECTIVE: It is unclear if vitamin D supplementation improves central blood
      pressure or arterial stiffness in Native American (NA) women. METHODS: Healthy
      postmenopausal NA women were randomized to receive 400 IU or 2500 IU of vitamin D
      for 6 months. Central systolic blood pressure (cSBP), central pulse pressure
      (cPP) and aortic augmentation index (AIx) were estimated by tonometry at baseline
      and after 6 months. RESULTS: Study volunteers (n = 98) were 61 (7.3) years old.
      25(OH)D was 26.4 (11.0) ng/mL. 25(OH)D was similar between the two treatment
      groups (p = 0.291), as were baseline cSBP, cPP, and CVD risk factors (all p >
      0.1). Treatment with 2500 IU of daily vitamin D3 did not affect cSBP, cPP, or AIx
      (all p > 0.1) compared to 400 IU daily. CONCLUSIONS: Despite low serum 25(OH)D at
      baseline, 6 months of vitamin D supplementation did not improve central blood
      pressure parameters or arterial stiffness in NA women. CLINICAL TRIALS. GOV
      IDENTIFIER: NCT01490333.

PMID- 25955193
TI  - Design, synthesis, photophysical and electrochemical properties of 2-(4,5
      diphenyl-1-p-aryl-1H-imidazol-2-yl)phenol-based boron complexes.
AB  - New hybrid organic-inorganic boron compounds using an imidazole core have been
      readily synthesized by a two-step procedure from commercially available simple
      starting materials. All boron compounds were fully characterized by multinuclear
      NMR spectroscopy, LC-MS, thermogravimetric analysis, cyclic voltammetry and
      single crystal X-ray diffraction analysis (for & ). The photoluminescence
      measurements of revealed distinct emission peak maxima located at 378, 379 and
      387 nm, respectively. Electroluminescent devices fabricated using these boron
      compounds () suggest that the boron compounds are capable of transporting
      electrons. A maximum brightness of 6450 cd m(-2) at 12.5 V was realized when
      compound was used as an electron-transporting material. 

PMID- 25955192
TI  - Anxiety and depressive symptoms are associated with higher carotid intima-media
      thickness. Cross-sectional analysis from ELSA-Brasil baseline data.
AB  - BACKGROUND: Studies focusing on the association between anxiety/depressive
      symptoms and accelerated subclinical atherosclerosis have yielded mixed results.
      Our aim is to examine associations between anxiety/depressive symptoms, common
      mental disorder (CMD), major depression disorder (MDD) or generalized anxiety
      disorder (GAD) and carotid intima-media thickness (CIMT) in the Brazilian
      Longitudinal Study of Adult Health (ELSA-Brasil) cohort baseline. METHODS: The
      ELSA-Brasil baseline assessment included CIMT measurements and the Clinical
      Interview Schedule - Revised (CIS-R), a validated questionnaire for
      anxiety/depressive symptoms/diagnoses. We analyzed participants without previous
      coronary heart disease or stroke, and with high-quality CIMT images. We built
      regression models to determine whether the CIS-R score, CMD, MDD or GAD were
      associated with maximal CIMT levels. RESULTS: The study sample comprised 9744
      participants. We found that individuals with higher CIS-R scores (Odds ratio for
      one standard deviation increase [OR]:1.12; 95% confidence interval [95%CI]:1.06
      1.19), CMD (OR:1.22; 95%CI:1.07-1.38) and GAD (OR:1.19; 95%CI:1.01-1.41) had
      significantly higher odds of being classified in the highest age, sex and race
      specific CIMT quartile. In the linear models, after adjustment for traditional
      cardiovascular risk factors, higher CIS-R scores (beta:0.005; P = 0.010) and GAD
      (beta:0.010; P = 0.049) were independently associated with CIMT values.
      CONCLUSION: Individuals with more symptoms of anxiety and/or depression, or
      diagnoses of CMD or GAD, had higher CIMT values, compared to peers of same age,
      sex and race. CIS-R scores and GAD were independently associated with higher CIMT
      values. These results suggest an association between anxiety/depressive symptoms
      (and, most notably, GAD) and accelerated subclinical atherosclerosis.

PMID- 25955194
TI  - Fasting protects against the side effects of irinotecan but preserves its anti
      tumor effect in Apc15lox mutant mice.
AB  - Irinotecan is a widely used topoisomerase-I-inhibitor with a very narrow
      therapeutic window because of its severe toxicity. In the current study we have
      examined the effects of fasting prior to irinotecan treatment on toxicity and
      anti-tumor activity. FabplCre;Apc(15lox/+) mice, which spontaneously develop
      intestinal tumors, of 27 weeks of age were randomized into 3-day fasted and ad
      libitum fed groups, followed by treatment with a flat-fixed high dose of
      irinotecan or vehicle. Side-effects were recorded until 11 days after the start
      of the experiment. Tumor size, and markers for cell-cycle activity,
      proliferation, angiogenesis, and senescence were measured. Fasted mice were
      protected against the side-effects of irinotecan treatment. Ad libitum fed mice
      developed visible signs of discomfort including weight loss, lower activity,
      ruffled coat, hunched-back posture, diarrhea, and leukopenia. Irinotecan reduced
      tumor size in fasted and ad libitum fed groups similarly compared to untreated
      controls (2.4 +/- 0.67 mm and 2.4 +/- 0.82 mm versus 3.0 +/- 1.05 mm and 2.8 +/-
      1.08 mm respectively, P < 0.001). Immunohistochemical analysis showed reduced
      proliferation, a reduced number of vascular endothelial cells, and increased
      levels of senescence in tumors of both irinotecan treated groups. In conclusion,
      3 days of fasting protects against the toxic side-effects of irinotecan in a
      clinically relevant mouse model of spontaneously developing colorectal cancer
      without affecting its anti-tumor activity. These results support fasting as a
      powerful way to improve treatment of colorectal carcinoma patients.

PMID- 25955195
TI  - Impact of insurance carrier, prior authorization, and socioeconomic status on
      appropriate use of SPECT myocardial perfusion imaging in private community-based
      office practice.
AB  - BACKGROUND: The impact of health insurance carrier and socioeconomic status (SES)
      on the adherence to appropriate use criteria (AUC) for radionuclide myocardial
      perfusion imaging (MPI) is unknown. HYPOTHESIS: Health insurance carrier's prior
      authorization and patient's SES impact adherence to AUC for MPI in a fee-for
      service setting. METHODS: We conducted a prospective cohort study of 1511
      consecutive patients who underwent outpatient MPI in a multi-site, office-based,
      fee-for-service setting. The patients were stratified according to the 2009 AUC
      into appropriate/uncertain appropriateness and inappropriate use groups.
      Insurance status was categorized as Medicare (does not require prior
      authorization) vs commercial (requires prior authorization). Socioeconomic status
      was determined by the median household income in the ZIP code of residence.
      RESULTS: The proportion of patients with Medicare was 33% vs 67% with commercial
      insurance. The rate of inappropriate use was higher among patients with
      commercial insurance vs Medicare (55% vs 24%; P < 0.001); this difference was not
      significant after adjusting for confounders known to impact AUC determination
      (odds ratio: 1.06, 95% confidence interval: 0.62-1.82, P = 0.82). The mean annual
      household income in the residential areas of patients with inappropriate use as
      compared to those with appropriate/uncertain use was $72 000 +/- 21 000 vs $68
      000 +/- 20 000, respectively (P < 0.001). After adjusting for covariates known to
      impact AUC determination, SES (top vs bottom quartile income area) was not
      independently predictive of inappropriate MPI use (odds ratio: 0.9, 95%
      confidence interval: 0.53-1.52, P = 0.69). CONCLUSIONS: Insurance carriers prior
      authorization and SES do not seem to play a significant role in determining
      physicians adherence to AUC for MPI.

PMID- 25955196
TI  - The Impact of Relationship Quality on Health-Related Outcomes in Heart Failure
      Patients and Informal Family Caregivers: An Integrative Review.
AB  - BACKGROUND: Relationships can have positive and negative impacts on health and
      well-being. Dyadic relationships between heart failure (HF) patients and their
      informal family caregivers may affect both patient and caregiver outcomes.
      OBJECTIVE: The aim of this study is to synthesize the literature to date on the
      associations between HF patient-caregiver relationship quality and communication
      and patient and caregiver health outcomes. METHODS: An integrative review of the
      literature was conducted. Computerized literature searches in Medline, PsycInfo,
      CINAHL, Web of Science, and EMBASE yielded 13 articles of HF patients and
      caregivers. Included articles were reviewed and double-coded by 2 independent
      coders. RESULTS: Included articles measured relationship quality or aspects of
      communication within an HF patient-caregiver dyad and used both cross-sectional
      and longitudinal designs. Results of the longest prospective study suggested that
      better relationship quality between HF patients and their informal family
      caregivers was related to a reduced risk for mortality in patients. Results of 11
      of the 12 other studies were consistent to the reference study, suggesting that
      better relationship quality and communication were related to reduced mortality,
      increased health status, less distress, and lower caregiver burden. CONCLUSIONS:
      Relationship quality and communication seem to matter in the health and well
      being of both HF patients and their informal family caregivers. More research is
      needed to elucidate mechanisms and to design effective relationship-focused
      interventions.

PMID- 25955197
TI  - Welcome to Cell Metabolism's "Rosie Project".

PMID- 25955198
TI  - Ether lipid deficiency does not cause neutropenia or leukopenia in mice and men.
AB  - In this Letter, Dorninger et al. show that the deficiency in ether lipid
      biosynthesis alone is not sufficient to induce neutropenia or leukopenia, as has
      been suggested by a previous report using an inducible knockout mouse model of
      ether lipid deficiency. 

PMID- 25955199
TI  - Acute ether lipid deficiency affects neutrophil biology in mice.

PMID- 25955200
TI  - Adult stem-like cells exclude "older" mitochondria.
AB  - Asymmetric distribution of damaged cellular constituents may occur during
      mitosis, resulting in more and less pristine daughter cell pairs. In Science,
      Katajisto et al., (2015) report that mammary stem-like cells (SLCs) unequally
      apportion older mitochondria to post-division daughter cells, with the daughter
      containing younger mitochondria maintaining the SLC pool. 

PMID- 25955201
TI  - Mic10 Oligomerization Pinches off Mitochondrial Cristae.
AB  - The mitochondrial contact site and cristae organizing system (MICOS) complex is
      essential for normal mitochondria biogenesis and morphology. In this issue,
      Bohnert et al. (2015) and Barbot et al. (2015) demonstrate that a MICOS core
      subunit, Mic10, is crucial for mitochondrial cristae formation by forming
      oligomers at the cristae junctions. 

PMID- 25955202
TI  - Modeling the aging heart: from local respiratory defects to global rhythm
      disturbances.
AB  - In this issue, Baris et al. (2015) describe cardiac rhythm abnormalities in a
      mouse model of mitochondrial dysfunction in widely distributed cells of the aging
      human heart. How do a few metabolically challenged cells disrupt cardiac rhythm?
      We suggest that these cells provide "crystallization centers" for latent
      dysfunctional zones to allow arrhythmia emergence. 

PMID- 25955203
TI  - Come to Where Insulin Resistance Is, Come to AMPK Country.
AB  - The link between smoking and insulin resistance, despite weight loss, is well
      established; however, the underlying mechanisms remain elusive. A recent article
      published in Nature Medicine by Wu et al. (2015) reports that nicotine, the main
      bioactive component of tobacco smoke, activates AMPKalpha2 in adipocytes, leading
      to impaired insulin sensitivity. 

PMID- 25955204
TI  - Mosaic Deficiency in Mitochondrial Oxidative Metabolism Promotes Cardiac
      Arrhythmia during Aging.
AB  - Aging is a progressive decline of body function, during which many tissues
      accumulate few cells with high levels of deleted mitochondrial DNA (mtDNA),
      leading to a defect of mitochondrial functions. Whether this mosaic mitochondrial
      deficiency contributes to organ dysfunction is unknown. To investigate this, we
      generated mice with an accelerated accumulation of mtDNA deletions in the
      myocardium, by expressing a dominant-negative mutant mitochondrial helicase.
      These animals accumulated few randomly distributed cardiomyocytes with
      compromised mitochondrial function, which led to spontaneous ventricular
      premature contractions and AV blocks at 18 months. These symptoms were not caused
      by a general mitochondrial dysfunction in the entire myocardium, and were not
      observed in mice at 12 months with significantly lower numbers of dysfunctional
      cells. Therefore, our results suggest that the disposition to arrhythmia
      typically found in the aged human heart might be due to the random accumulation
      of mtDNA deletions and the subsequent mosaic respiratory chain deficiency. 

PMID- 25955205
TI  - Hematopoietic Kit Deficiency, rather than Lack of Mast Cells, Protects Mice from
      Obesity and Insulin Resistance.
AB  - Obesity, insulin resistance, and related pathologies are associated with immune
      mediated chronic inflammation. Kit mutant mice are protected from diet-induced
      obesity and associated co-morbidities, and this phenotype has previously been
      attributed to their lack of mast cells. We performed a comprehensive metabolic
      analysis of Kit-dependent Kit(W/Wv) and Kit-independent Cpa3(Cre/+) mast-cell
      deficient mouse strains, employing diet-induced or genetic (Lep(Ob/Ob)
      background) models of obesity. Our results show that mast cell deficiency, in the
      absence of Kit mutations, plays no role in the regulation of weight gain or
      insulin resistance. Moreover, we provide evidence that the metabolic phenotype
      observed in Kit mutant mice, while independent of mast cells, is immune
      regulated. Our data underscore the value of definitive mast cell deficiency
      models to conclusively test the involvement of this enigmatic cell in immune
      mediated pathologies and identify Kit as a key hematopoietic factor in the
      pathogenesis of metabolic syndrome. 

PMID- 25955206
TI  - Central serotonergic neurons activate and recruit thermogenic brown and beige fat
      and regulate glucose and lipid homeostasis.
AB  - Thermogenic brown and beige adipocytes convert chemical energy to heat by
      metabolizing glucose and lipids. Serotonin (5-HT) neurons in the CNS are
      essential for thermoregulation and accordingly may control metabolic activity of
      thermogenic fat. To test this, we generated mice in which the human diphtheria
      toxin receptor (DTR) was selectively expressed in central 5-HT neurons. Treatment
      with diphtheria toxin (DT) eliminated 5-HT neurons and caused loss of
      thermoregulation, brown adipose tissue (BAT) steatosis, and a >50% decrease in
      uncoupling protein 1 (Ucp1) expression in BAT and inguinal white adipose tissue
      (WAT). In parallel, blood glucose increased 3.5-fold, free fatty acids 13.4-fold,
      and triglycerides 6.5-fold. Similar BAT and beige fat defects occurred in
      Lmx1b(f/f)ePet1(Cre) mice in which 5-HT neurons fail to develop in utero. We
      conclude 5-HT neurons play a major role in regulating glucose and lipid
      homeostasis, in part through recruitment and metabolic activation of brown and
      beige adipocytes. 

PMID- 25955207
TI  - The CDP-Ethanolamine Pathway Regulates Skeletal Muscle Diacylglycerol Content and
      Mitochondrial Biogenesis without Altering Insulin Sensitivity.
AB  - Accumulation of diacylglycerol (DG) in muscle is thought to cause insulin
      resistance. DG is a precursor for phospholipids, thus phospholipid synthesis
      could be involved in regulating muscle DG. Little is known about the interaction
      between phospholipid and DG in muscle; therefore, we examined whether disrupting
      muscle phospholipid synthesis, specifically phosphatidylethanolamine (PtdEtn),
      would influence muscle DG content and insulin sensitivity. Muscle PtdEtn
      synthesis was disrupted by deleting CTP:phosphoethanolamine cytidylyltransferase
      (ECT), the rate-limiting enzyme in the CDP-ethanolamine pathway, a major route
      for PtdEtn production. While PtdEtn was reduced in muscle-specific ECT knockout
      mice, intramyocellular and membrane-associated DG was markedly increased.
      Importantly, however, this was not associated with insulin resistance.
      Unexpectedly, mitochondrial biogenesis and muscle oxidative capacity were
      increased in muscle-specific ECT knockout mice and were accompanied by enhanced
      exercise performance. These findings highlight the importance of the CDP
      ethanolamine pathway in regulating muscle DG content and challenge the DG-induced
      insulin resistance hypothesis. 

PMID- 25955208
TI  - Pharmacologic Effects of FGF21 Are Independent of the "Browning" of White Adipose
      Tissue.
AB  - "Browning," the appearance and activation of brown-in-white (brite) adipose cells
      within inguinal white adipose tissue (iWAT), and induction of uncoupling protein
      1 (UCP1) correlate with fibroblast growth factor-21 (FGF21)-induced weight loss
      and glucose homeostasis improvements. Therefore, antiobesity therapies targeting
      browning and brite adipocyte activation are currently being sought. To test the
      dependence of weight loss on browning, we examined whether this event was
      responsible for FGF21-Fc's beneficial effects. Lean and diet-induced obese mice
      housed at 21 degrees C or 30 degrees C that received FGF21-Fc exhibited similar
      degrees of body weight reduction and glucose homeostasis improvement. Substantial
      browning of iWAT occurred only in FGF21-Fc-treated lean mice housed at 21 degrees
      C. Further, FGF21-Fc-treated Ucp1(-/-) mice showed robust improvements in body
      weight, glucose homeostasis, and plasma lipids, associated with increased energy
      expenditure and FGF21-Fc-induced Ppargc1 expression in iWAT. We conclude that
      FGF21 requires neither UCP1 nor brite adipocytes to elicit weight loss and
      improve glucose homeostasis. 

PMID- 25955209
TI  - Adaptation of hepatic mitochondrial function in humans with non-alcoholic fatty
      liver is lost in steatohepatitis.
AB  - The association of hepatic mitochondrial function with insulin resistance and non
      alcoholic fatty liver (NAFL) or steatohepatitis (NASH) remains unclear. This
      study applied high-resolution respirometry to directly quantify mitochondrial
      respiration in liver biopsies of obese insulin-resistant humans without (n = 18)
      or with (n = 16) histologically proven NAFL or with NASH (n = 7) compared to lean
      individuals (n = 12). Despite similar mitochondrial content, obese humans with or
      without NAFL had 4.3- to 5.0-fold higher maximal respiration rates in isolated
      mitochondria than lean persons. NASH patients featured higher mitochondrial mass,
      but 31%-40% lower maximal respiration, which associated with greater hepatic
      insulin resistance, mitochondrial uncoupling, and leaking activity. In NASH,
      augmented hepatic oxidative stress (H2O2, lipid peroxides) and oxidative DNA
      damage (8-OH-deoxyguanosine) was paralleled by reduced anti-oxidant defense
      capacity and increased inflammatory response. These data suggest adaptation of
      the liver ("hepatic mitochondrial flexibility") at early stages of obesity
      related insulin resistance, which is subsequently lost in NASH. 

PMID- 25955210
TI  - Central role of Mic10 in the mitochondrial contact site and cristae organizing
      system.
AB  - The mitochondrial contact site and cristae organizing system (MICOS) is a
      conserved multi-subunit complex crucial for maintaining the characteristic
      architecture of mitochondria. Studies with deletion mutants identified Mic10 and
      Mic60 as core subunits of MICOS. Mic60 has been studied in detail; however,
      topogenesis and function of Mic10 are unknown. We report that targeting of Mic10
      to the mitochondrial inner membrane requires a positively charged internal loop,
      but no cleavable presequence. Both transmembrane segments of Mic10 carry a
      characteristic four-glycine motif, which has been found in the ring-forming rotor
      subunit of F1Fo-ATP synthases. Overexpression of Mic10 profoundly alters the
      architecture of the inner membrane independently of other MICOS components. The
      four-glycine motifs are dispensable for interaction of Mic10 with other MICOS
      subunits but are crucial for the formation of large Mic10 oligomers. Our studies
      identify a unique role of Mic10 oligomers in promoting the formation of inner
      membrane crista junctions. 

PMID- 25955211
TI  - Mic10 oligomerizes to bend mitochondrial inner membranes at cristae junctions.
AB  - The mitochondrial inner membrane is highly folded and displays a complex
      molecular architecture. Cristae junctions are highly curved tubular openings that
      separate cristae membrane invaginations from the surrounding boundary membrane.
      Despite their central role in many vital cellular processes like apoptosis, the
      details of cristae junction formation remain elusive. Here we identify Mic10, a
      core subunit of the recently discovered MICOS complex, as an inner mitochondrial
      membrane protein with the ability to change membrane morphology in vitro and in
      vivo. We show that Mic10 spans the inner membrane in a hairpin topology and that
      its ability to sculpt membranes depends on oligomerization through a glycine-rich
      motif. Oligomerization mutants fail to induce curvature in model membranes, and
      when expressed in yeast, mitochondria display an altered inner membrane
      architecture characterized by drastically decreased numbers of cristae junctions.
      Thus, we demonstrate that membrane sculpting by Mic10 is essential for cristae
      junction formation. 

PMID- 25955213
TI  - Recent progress in developing proximity ligation assays for pathogen detection.
AB  - The effective management of infectious diseases depends on the early detection of
      the microbes responsible, since pathogens are most effectively eliminated in the
      initial stages of infection. Current immunodiagnostic methods lack the
      sensitivity for earliest possible diagnosis. Nucleic acid-based tests (NATs) are
      more sensitive, but the detection of microbial DNA does not definitively prove
      the presence of a viable microorganism capable of causing a given infection.
      Proximity assays combine the specificity of antibody-based detection of proteins
      with the sensitivity and dynamic range of NATs, and their use may allow earlier
      as well as more clinically relevant detection than is possible with current NATs
      or immunoassays. However, the full potential of proximity assays for pathogen
      detection remains to be fulfilled, mainly due to the challenges associated with
      identifying suitable antibodies and antibody combinations, sensitivity issues
      arising from non-specific interactions of proximity probes and the longer
      incubation times required to carry out the assays. 

PMID- 25955214
TI  - Factors predictive of type of powered mobility received by veterans with
      disability.
AB  - BACKGROUND: The goal of this observational study was to determine factors
      predictive of the type of powered mobility prescribed to veterans with
      disability. MATERIAL/METHODS: A retrospective chart review was conducted for all
      veterans (n=170) who received powered mobility from a designated power mobility
      clinic. Logistic regression analysis was used to determined factors predictive of
      the type of powered mobility provided. RESULTS: Sixty-four (38%) veterans were
      provided powered wheelchairs and 106 (62%) were provided powered scooters. Of the
      variables examined, only primary medical conditions for referral and disability
      severity (as measured by the 2-minute timed walk test; 2-MWT) were predictive of
      the types of powered mobility prescribed. Veterans who were able to walk longer
      distances were more likely to be prescribed powered scooters. Age, gender, race,
      level of education, marital and employment status, number of chronic medical
      conditions, and upper and lower limb muscle strength were not significant
      predictors. CONCLUSIONS: This study suggests that the primary medical conditions
      for referral and 2-MWT can assist clinicians in the determination of the type of
      powered mobility to prescribe to veterans with disability.

PMID- 25955212
TI  - SoNar, a Highly Responsive NAD+/NADH Sensor, Allows High-Throughput Metabolic
      Screening of Anti-tumor Agents.
AB  - The altered metabolism of tumor cells confers a selective advantage for survival
      and proliferation, and studies have shown that targeting such metabolic shifts
      may be a useful therapeutic strategy. We developed an intensely fluorescent,
      rapidly responsive, pH-resistant, genetically encoded sensor of wide dynamic
      range, denoted SoNar, for tracking cytosolic NAD(+) and NADH redox states in
      living cells and in vivo. SoNar responds to subtle perturbations of various
      pathways of energy metabolism in real time, and allowed high-throughput screening
      for new agents targeting tumor metabolism. Among > 5,500 unique compounds, we
      identified KP372-1 as a potent NQO1-mediated redox cycling agent that produced
      extreme oxidative stress, selectively induced cancer cell apoptosis, and
      effectively decreased tumor growth in vivo. This study demonstrates that
      genetically encoded sensor-based metabolic screening could serve as a valuable
      approach for drug discovery. 

PMID- 25955046
TI  - Search for Scalar Charm Quark Pair Production in pp Collisions at sqrt[s]=8  TeV
      with the ATLAS Detector.
AB  - The results of a dedicated search for pair production of scalar partners of charm
      quarks are reported. The search is based on an integrated luminosity of 20.3 
      fb^{-1} of pp collisions at sqrt[s]=8  TeV recorded with the ATLAS detector at
      the LHC. The search is performed using events with large missing transverse
      momentum and at least two jets, where the two leading jets are each tagged as
      originating from c quarks. Events containing isolated electrons or muons are
      vetoed. In an R-parity-conserving minimal supersymmetric scenario in which a
      single scalar-charm state is kinematically accessible, and where it decays
      exclusively into a charm quark and a neutralino, 95% confidence-level upper
      limits are obtained in the scalar-charm-neutralino mass plane such that, for
      neutralino masses below 200 GeV, scalar-charm masses up to 490 GeV are excluded. 

PMID- 25955215
TI  - Childcare use and overweight in Finland: cross-sectional and retrospective
      associations among 3- and 5-year-old children.
AB  - BACKGROUND: Different types of non-parental childcare have been found to
      associate with childhood overweight in several, but not all studies. Studies on
      the matter are mainly North American. OBJECTIVES: The objective of our study was
      to examine associations between childcare use and overweight in Finland. METHODS:
      The cross-sectional and partly retrospective data consists of 1683 3- and 5-year
      old children participating in the Child Health Monitoring Development project
      (LATE-project) conducted in 2007-2009 in Finland. Children were measured at
      health check-ups and information on child's age when entering childcare, the
      number of childcare places the child has had, current type of childcare
      (parental, informal, [group] family childcare, childcare centre) and the current
      amount of childcare (hours) were gathered. Parents' body mass indices, family
      educational level, family structure, maternal smoking during pregnancy and
      child's birth weight were treated as covariates. RESULTS: Beginning childcare
      before age 1 (adjusted model: odds ratio [OR] 2.53, 95% confidence interval [CI]
      1.41-4.52) and, for girls only, number of childcare places (adjusted model: OR
      1.33, 95% CI 1.11-1.60), were associated with an increased risk of overweight.
      The current type of childcare or the time currently spent in childcare was not
      associated with overweight. CONCLUSION: Beginning childcare before age 1, which
      is quite rare in Finland, and having attended several childcare places were
      associated with overweight even when adjusting for family socioeconomic status
      and other family background variables. The significance of these findings needs
      to be further studied.

PMID- 25955216
TI  - Cadmium-induced autophagy promotes survival of rat cerebral cortical neurons by
      activating class III phosphoinositide 3-kinase/beclin-1/B-cell lymphoma 2
      signaling pathways.
AB  - Autophagy is an evolutionarily conserved response that can be activated in
      response to heavy metal. Thus, the present study investigated the effect of
      autophagy on neurotoxic damage caused by cadmium (Cd) in rat cerebral cortical
      neurons. The results indicated that the viability of cortical neurons treated
      with Cd was markedly decreased in a dose-and time-dependent manner. The present
      study provided evidence that cortical neurons treated with Cd underwent
      autophagy: The conversion of microtubule-associated protein 1A/1B-light chain 3
      (LC3) to LC3-II, an increase in the punctate distribution of endogenous LC3-II
      and the presence of autophagosomes were identified. Combined treatment with Cd
      and chloroquine, an autophagy inhibitor, reduced the amount of autophagocytosis
      and cell activity, whereas rapamycin, an autophagy inducer, reduced Cd-mediated
      cytotoxicity. Furthermore, it was found that beclin-1 and class III
      phosphoinositide 3 kinase (PI3K) levels were increased, while levels of the anti
      apoptotic protein B-cell lymphoma 2 (Bcl-2) were decreased after Cd treatment.
      LY294002, a specific inhibitor of PI3K, prevented the decline in Bcl-2 production
      and the increase in levels of beclin-1, class III PI3K and autophagy following Cd
      treatment. In conclusion, the results of the present study suggested that Cd can
      induce cytoprotective autophagy by activating the class III PI3K/beclin-1/Bcl-2
      signaling pathway, and that the autophagy pathway can serve as a sensitive
      biomarker for nervous system injury after exposure to Cd.

PMID- 25955219
TI  - 1157 Academic dissertations in psychiatry in Sweden 1858-2012.

PMID- 25955217
TI  - Discrimination of various paper types using diffuse reflectance ultraviolet
      visible near-infrared (UV-Vis-NIR) spectroscopy: forensic application to
      questioned documents.
AB  - Diffuse reflectance ultraviolet-visible-near-infrared (UV-Vis-NIR) spectroscopy
      is applied as a means of differentiating various types of writing, office, and
      photocopy papers (collected from stationery shops in India) on the basis of
      reflectance and absorbance spectra that otherwise seem to be almost alike in
      different illumination conditions. In order to minimize bias, spectra from both
      sides of paper were obtained. In addition, three spectra from three different
      locations (from one side) were recorded covering the upper, middle, and bottom
      portions of the paper sample, and the mean average reflectivity of both the sides
      was calculated. A significant difference was observed in mean average
      reflectivity of Side A and Side B of the paper using Student's pair >t-test.
      Three different approaches were used for discrimination: (1) qualitative features
      of the whole set of samples, (2) principal component analysis, and (3) a
      combination of both approaches. On the basis of the first approach, i.e.,
      qualitative features, 96.49% discriminating power (DP) was observed, which shows
      highly significant results with the UV-Vis-NIR technique. In the second approach
      the discriminating power is further enhanced by incorporating the principal
      component analysis (PCA) statistical method, where this method describes each UV
      Vis spectrum in a group through numerical loading values connected to the first
      few principal components. All components described 100% variance of the samples,
      but only the first three PCs are good enough to explain the variance (PC1 =
      51.64%, PC2 = 47.52%, and PC3 = 0.54%) of the samples; i.e., the first three PCs
      described 99.70% of the data, whereas in the third approach, the four samples, C,
      G, K, and N, out of a total 19 samples, which were not differentiated using
      qualitative features (approach no. 1), were therefore subjected to PCA. The first
      two PCs described 99.37% of the spectral features. The discrimination was
      achieved by using a loading plot between PC1 and PC2. It is therefore concluded
      that maximum discrimination of writing, office, and photocopy paper could be
      achieved on the basis of the second approach. Hence, the present inexpensive
      analytical method can be appropriate for application to routine questioned
      document examination work in forensic laboratories because it provides
      nondestructive, quantitative, reliable, and repeatable results. 

PMID- 25955220
TI  - Tuning Cerium(IV)-Assisted Hydrolysis of Phosphatidylcholine Liposomes under
      Mildly Acidic and Neutral Conditions.
AB  - With the goal of designing a lysosomal phospholipase mimic, we optimized
      experimental variables to enhance Ce(IV) -assisted hydrolysis of
      phosphatidylcholine (PC) liposomes. Our best result was obtained with the
      chelating agent bis-tris propane (BTP). Similar to the hydrolytic enzyme, Ce(IV) 
      assisted hydrolysis of PC phosphate ester bonds was higher at lysosomal pH (~4.8)
      compared to pH 7.2. In the presence of BTP, the average cleavage yield at ~pH 4.8
      and 37  degrees C was: 67+/-1 %, 5.7-fold higher than at ~pH 7.2 and roughly
      equivalent to the percent of phospholipid found on the metal-accessible exo
      leaflet of small liposomes. No Ce(IV) precipitation was observed. When BTP was
      absent, there was significant turbidity, and the amount of cleavage at ~pH 4.8
      (69+/-1 %) was 2.1-fold higher than the yield obtained at ~pH 7.2. Our results
      show that BTP generates homogenous solutions of Ce(IV) that hydrolyze
      phosphatidylcholine with enhanced selectivity for lysosomal pH. 

PMID- 25955221
TI  - Pre-Use Susceptibility to Ceftaroline in Clinical Staphylococcus aureus Isolates
      from Germany: Is There a Non-Susceptible Pool to be Selected?
AB  - Ceftaroline is a new cephalosporin active against Methicillin-resistant
      Staphylococcus aureus (MRSA). Based on a representative collection of clinical S.
      aureus isolates from Germany, supplemented with isolates of clonal lineages ST228
      and ST239, we demonstrate the in-vitro susceptibility towards ceftaroline prior
      to its introduction into clinical use for a total of 219 isolates. Susceptibility
      testing was performed by broth microdilution, disc diffusion and Etest,
      respectively. Results were interpreted according to EUCAST guidelines and showed
      considerable variance in dependence on clonal affiliation of the isolates tested.
      Among isolates of widespread hospital-associated lineages we found a high
      proportion of clinical isolates with MICs close to the EUCAST breakpoint
      (MIC50/90 1.0/1.5 mg/L); currently, interpretation of these "borderline" MICs is
      complicated by a lack of concordant susceptibility testing methods and reasonable
      breakpoint determination. Isolates of clonal lineages ST228 and ST239
      demonstrated increased MIC50/90 values of 2.5/3.33 mg/L. Sequencing of mecA
      revealed no association of resistance to a specific mecA polymorphism, but rather
      reveals two regions in the non-penicillin-binding domain of PbP2a which displayed
      different combinations of mutations putatively involved in resistance
      development. This study provides national baseline data to (i) adjust
      susceptibility testing methods and current breakpoints to clinical and
      epidemiological requirements, (ii) evaluate current breakpoints with respect to
      therapeutic outcome and (iii) monitor further resistance evolution. 

PMID- 25955218
TI  - Dissecting the roles of Ephrin-A3 in malignant peripheral nerve sheath tumor by
      TALENs.
AB  - Malignant peripheral nerve sheath tumor (MPNST) is a rare and aggressive soft
      tissue sarcoma for which effective treatments have not yet been established due
      to poor understanding of its pathogenesis. Our previous study indicated that miR
      210-mediated Ephrin-A3 (EFNA3) promotion of proliferation and invasion of MPNST
      cells plays an important role in MPNST tumorigenesis and progression. The purpose
      of the present study was to further investigate the roles of EFNA3 in MPNST.
      Constructed transcription activator-like effector nucleases (TALENs) and
      lentiviral vectors were transfected into MPNST ST88-14 (NF1 wild-type) and
      sNF96.2 (NF1 mutant type) cell lines to obtain gain- and loss-of-function cell
      lines for the EFNA3 function study. The results showed that the knockout of ENFA3
      increased cellular viability and invasiveness of the MPNST cells. However, the
      adhesion ability of MPNST cells was enhanced or inhibited when EFNA3 was
      overexpressed or knocked out, respectively. It was also observed that knockout of
      EFNA3 significantly decreased the expression of phosphorylated FAK (p-FAK) and
      the tumor necrosis factor alpha (TNF-alpha) compared to that in the control
      cells, yet the expression of phosphatidylinositol 3-kinase (PI3K), GTPase,
      integrins, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor
      1alpha (HIF-alpha) increased significantly. Inversely, overexpression of EFNA3
      significantly increased the expression of p-FAK and TNF-alpha compared to that in
      the control cells, yet the expression of PI3K, GTPase, integrins, VEGF and HIF
      alpha decreased significantly. The results indicated that EFNA3 serves as a tumor
      suppressor in MPNST cells and it may play a critical role in the focal adhesion
      kinase (FAK) signaling and VEGF-associated tumor angiogenesis pathway. These
      findings may not only facilitate the better understanding of MPNST pathogenesis,
      but also suggest EFNA3 as a promising target for MPNST treatment.

PMID- 25955222
TI  - Role of the mouse retinal photoreceptor ribbon synapse in visual motion
      processing for optokinetic responses.
AB  - The ribbon synapse is a specialized synaptic structure in the retinal outer
      plexiform layer where visual signals are transmitted from photoreceptors to the
      bipolar and horizontal cells. This structure is considered important in high
      efficiency signal transmission; however, its role in visual signal processing is
      unclear. In order to understand its role in visual processing, the present study
      utilized Pikachurin-null mutant mice that show improper formation of the
      photoreceptor ribbon synapse. We examined the initial and late phases of the
      optokinetic responses (OKRs). The initial phase was examined by measuring the
      open-loop eye velocity of the OKRs to sinusoidal grating patterns of various
      spatial frequencies moving at various temporal frequencies for 0.5 s. The mutant
      mice showed significant initial OKRs with a spatiotemporal frequency tuning
      (spatial frequency, 0.09 +/- 0.01 cycles/ degrees ; temporal frequency, 1.87 +/-
      0.12 Hz) that was slightly different from the wild-type mice (spatial frequency,
      0.11 +/- 0.01 cycles/ degrees ; temporal frequency, 1.66 +/- 0.12 Hz). The late
      phase of the OKRs was examined by measuring the slow phase eye velocity of the
      optokinetic nystagmus induced by the sinusoidal gratings of various
      spatiotemporal frequencies moving for 30 s. We found that the optimal spatial and
      temporal frequencies of the mutant mice (spatial frequency, 0.11 +/- 0.02 cycles/
      degrees ; temporal frequency, 0.81 +/- 0.24 Hz) were both lower than those in the
      wild-type mice (spatial frequency, 0.15 +/- 0.02 cycles/ degrees ; temporal
      frequency, 1.93 +/- 0.62 Hz). These results suggest that the ribbon synapse
      modulates the spatiotemporal frequency tuning of visual processing along the ON
      pathway by which the late phase of OKRs is mediated. 

PMID- 25955223
TI  - Hypercalciuria May Persist After Successful Parathyroid Surgery and It Is
      Associated With Parathyroid Hyperplasia.
AB  - CONTEXT: Hypercalciuria is frequently found in primary hyperparathyroidism (1HPT)
      and, although it generally normalizes after successful parathyroidectomy, may
      persist in some patients. The factors associated with persistent calcium renal
      leak (cRL) have not been clarified. OBJECTIVE: The purpose of this study was to
      determine the prevalence of cRL in our 1HPT population and investigate cRL
      related factors. DESIGN: This was a retrospective longitudinal study. SETTING:
      The study was conducted in an outpatient setting. PATIENTS/INTERVENTION: The
      participants were 95 patients with 1HPT successfully operated on who had a normal
      estimated glomerular filtration rate. MAIN OUTCOME MEASURES: The biochemical
      parameters of calcium metabolism and bone mineral density (BMD) measured by dual
      X-ray absorptiometry before and 24 months after surgery were assessed. All
      histological findings were recorded. RESULTS: The prevalence of hypercalciuria
      before and after surgery was 74% and 32%, respectively. Before, surgery patients
      with cRL showed lower calcium and higher phosphate levels than those without cRL
      (10.9 +/- 0.6 vs 11.4 +/- 0.8 mg/dL [2.7 +/- 0.2 vs 2.8 +/- 0.2 mmol/L], P = .01
      and 2.6 +/- 0.5 vs 2.4 +/- 0.4 mg/dL [0.84 +/- 0.2 vs 0.77 +/- 0.1 mmol/L], P =
      .04, respectively), whereas 24-h calciuria levels and the prevalence of 1HPT
      complications (osteoporosis, renal stones, and hypertension) were comparable.
      After surgery, serum calcium, phosphate, and PTH levels were comparable between
      patients with and without cRL. The prevalence of the histological finding of
      parathyroid hyperplasia was higher in patients with cRL (50%) than in patients
      without cRL (22%) (P = .01). The presence of cRL was independently associated
      with presurgery hypercalciuria (odds ratio, 4.71; 95% confidence interval, 1.18
      18.8; P = .03) and parathyroid hyperplasia (odds ratio, 3.52; 95% confidence
      interval, 1.31-9.43; P = .01). Only patients without cRL had improved BMD at the
      spine (P = .04), total femur (P = .01), and femoral neck (P = .01). CONCLUSIONS:
      cRL is present in 30% of patients with 1HPT after successful surgery, and it is
      associated with parathyroid hyperplasia before surgery and the lack of
      improvement in BMD after surgery.

PMID- 25955224
TI  - Antral Follicle Priming Before Intracytoplasmic Sperm Injection in Previously
      Diagnosed Low Responders: A Randomized Controlled Trial (FOLLPRIM).
AB  - CONTEXT: A low response to controlled ovarian hyperstimulation implies a reduced
      number of embryos and impaired pregnancy rate. Follicular priming with steroids
      before controlled ovarian hyperstimulation has been suggested to improve the
      subsequent ovarian response. OBJECTIVE: The purpose of this study was to
      determine the best follicular priming protocol in low responders and to
      investigate the intrafollicular mechanisms triggered by steroid hormone priming.
      DESIGN: This was a single-center, randomized, parallel, open-label, controlled
      trial, in two phases. SETTING: The setting was a university-based in vitro
      fertilization unit. PATIENTS: Potential low responders (n = 99) underwent a first
      intracytoplasmic sperm injection cycle. Confirmed low responders (n = 66) were
      randomized to different priming protocols before a new intracytoplasmic sperm
      injection. INTERVENTIONS: Randomized patients underwent one of the following
      priming strategies: transdermal testosterone (20 MUg/kg/d), transdermal estradiol
      (200 MUg/d), or combined estrogens and oral contraceptive pills (30 MUg of
      ethinyl estradiol plus 150 MUg of desogestrel administered during the luteal
      phase of two consecutive cycles) and 4 mg/d of estradiol valerate during the
      follicular phase between them. MAIN OUTCOMES MEASURES: Metaphase II (MII) oocytes
      were retrieved. Gene expression levels in the granulosa cells of steroidogenesis
      enzymes and FSH, LH, and androgen receptors were measured. RESULTS: The number of
      retrieved MII oocytes did not differ between the interventional groups
      (testosterone, 2.2 +/- 2.0; estrogen, 2.7 +/- 1.7; and combined estrogens and
      oral contraceptive pills, 2.0 +/- 1.3; not significant). Compared with those in
      nonprimed cycles, estradiol pretreatment yielded more MII oocytes (primed, 2.7 +/
      1.7; nonprimed, 1.6 +/- 1.2; P = .029) although the clinical pregnancy rate was
      higher in patients treated with testosterone (P = .003). Testosterone
      pretreatment increased androgen receptor expression (P = .028) compared with that
      for the previous cycle without priming. CONCLUSIONS: The results of the present
      trial do not support the superiority of one priming strategy over the others.

PMID- 25955225
TI  - Effects of Denosumab and Calcitriol on Severe Secondary Hyperparathyroidism in
      Dialysis Patients With Low Bone Mass.
AB  - CONTEXT: Secondary hyperparathyroidism (SHPT) may worsen with administration of
      denosumab in chronic renal failure patients with low bone mass. OBJECTIVE: This
      study aimed to evaluate the short-term effect of coadministration of calcitriol
      and denosumab on PTH secretion and parathyroid structure and the incidence of
      adverse effects in patients with SHPT and low bone mass. DESIGN AND SETTING: This
      was a 24-week, open-label study at Kaohsiung Veterans General Hospital in
      Kaohsiung, Taiwan. PATIENTS: Dialysis patients with SHPT (intact parathyroid
      hormone [iPTH] > 800 pg/mL) and low bone mass (T score < -2.5) were enrolled.
      INTERVENTION: Patients received denosumab (60 mg) and doses of calcitriol
      adjusted to achieve iPTH < 300 pg/mL. MAIN OUTCOME MEASURES: Parathyroid gland
      volume was assessed upon study initiation and completion. Serum calcium,
      phosphate, alkaline phosphatase, iPTH, and adverse effects were assessed at each
      visit (Day 7, 14, and 21, and every month thereafter). RESULTS: iPTH
      significantly decreased (mean decrease, 58.28 +/- 6.12%) with
      denosumab/calcitriol administration (P < .01) but not in the controls (patients
      not receiving denosumab). Parathyroid gland volume decreased (mean decrease,
      21.98 +/- 5.54%) with denosumab/calcitriol administration (P < .01) and
      progressively increased (20.58 +/- 4.48%) in the controls (P < .05). Serum
      alkaline phosphatase and iPTH levels were significantly correlated to decreased
      iPTH and regression of parathyroid hyperplasia (P < .05). The most common adverse
      events were hypocalcemia (33.33%) and respiratory tract infection (4.17%).
      Hypocalcemia rapidly resolved with calcium and calcitriol supplements.
      CONCLUSIONS: Denosumab allows for supra-physiologic doses of calcitriol resulting
      in decreased parathyroid secretion and parathyroid hyperplasia. Supervised
      administration and weekly laboratory and clinical monitoring of serum calcium are
      recommended during the first month to prevent hypocalcemia.

PMID- 25955226
TI  - The Effect of Treatment With PTH on Undercarboxylated Osteocalcin and Energy
      Metabolism in Hypoparathyroidism.
AB  - CONTEXT: Undercarboxylated osteocalcin (ucOC) has been shown to affect glucose
      metabolism in mice. We recently randomized patients with hypoparathyroidism to
      treatment with PTH or placebo and demonstrated a marked increase in total
      osteocalcin. OBJECTIVE: To investigate whether there was a similar increase in
      ucOC and whether that increase affected glucose metabolism. DESIGN: A 24-week
      randomized, placebo-controlled trial. SETTING: Ambulatory patients in a research
      facility. PATIENTS: Sixty-two patients aged 31-78 years with hypoparathyroidism,
      of which 58 completed the trial. INTERVENTION: 100 MUg/d of PTH (1-84). MAIN
      OUTCOME MEASURE: Change in ucOC. RESULTS: ucOC increased by 1185.0 +/- 814.4%
      (mean +/- SD) in the PTH-treated group and by 69.3 +/- 79.4% in the placebo group
      (P < 10(-50)). In addition, body weight decreased by 1.1 +/- 4.0% in the
      treatment group and increased 0.8 +/- 2.5% in the placebo group (P = .04).
      Glucose, adiponectin, leptin, homeostasis model of assessment for insulin
      resistance, total body fat mass, or truncal fat did not change significantly. In
      addition, the number of hypercalcemic episodes per patient was 3.7 +/- 2.9 (mean
      +/- SD) in the PTH-treated group but only 0.2 +/- 0.6 in the placebo group (P <
      .001). Moreover, there was a significant and negative correlation between the
      change in ucOC and change in body weight (P = .004) or change in total body fat
      mass (P = .03), and a negative but nonsignificant correlation between the number
      of hypercalcemic episodes and percentage change in body weight (r = -0.32; P =
      .1). Change in ucOC did not significantly correlate with changes in other
      parameters. CONCLUSIONS: An explanation for the weight loss may be subtle
      hypercalcemia in PTH treatment inhibiting appetite. Our data do not support a
      role for ucOC in energy metabolism in humans.

PMID- 25955227
TI  - Primary and Secondary Hemostasis in Patients With Subclinical Hypothyroidism:
      Effect of Levothyroxine Treatment.
AB  - CONTEXT: Subclinical hypothyroidism (SH) is associated with some abnormalities in
      primary and secondary hemostasis. OBJECTIVE: The objective of the study was to
      evaluate changes in primary and secondary hemostasis induced by levothyroxine (L
      T4) treatment in SH patients. DESIGN: This was a prospective cohort study with a
      6-month follow-up. STUDY SETTING: Outpatients were referred to "Federico II"
      University of Naples. PATIENTS: Subjects with a SH without previous/ongoing L-T4
      therapy participated in the study. MAIN OUTCOME MEASURE: Changes in major
      hemostatic/fibrinolytic variables and platelet reactivity [mean platelet volume
      (MPV), arachidonic acid (AA), or ADP concentrations inducing a >= 50%
      irreversible aggregation (AC-50%)] in SH patients before and after a 6-month L-T4
      treatment. RESULTS: At baseline, 41 SH patients showed higher levels of factor
      VII activity (123.9 +/- 20.4 vs 107.7 +/- 12.2, P < .001), plasminogen activator
      inhibitor-1 (33.6 +/- 13.9 vs 22.5 +/- 5.74, P < .001) and tissue plasminogen
      activator (5.56 +/- 2.22 vs 4.75 +/- 1.61, P = .010), with lower levels of D
      dimer (220.3 +/- 67.1 vs 252.1 +/- 72.4, P = .017) compared with healthy
      controls. SH patients also showed a higher MPV (9.92 +/- 1.15 vs 8.9 +/- 0.9, P <
      .001) and AC-50% to AA (0.18 +/- 0.12 vs 0.36 +/- 0.10, P < .001) and to ADP (1.5
      +/- 0.6 vs 1.9 +/- 1.3, P = .024). After a 6-month L-T4 therapy, a reduction of
      factor VII activity (from 123.9 +/- 20.4 to 102.6 +/- 14.3, P < .001),
      plasminogen activator inhibitor-1 (33.6 +/- 13.9 to 19.4 +/- 7.6, P < .001), and
      tissue plasminogen activator (5.56 +/- 2.22 to 1.91 +/- 4:43, P = .002) was found
      in SH subjects, with a marginal increase in D-dimer (from 220.3 +/- 67.1 to 245.2
      +/- 103.1, P = .053). AC-50% to AA (from 0.18 +/- 0.12 to 0.54 +/- 0.3, P < .001)
      and to ADP (from 1.5 +/- 0.6 to 1.86 +/- 0.3, P = .042) were reduced, paralleled
      by a significant reduction of MPV (from 9.92 +/- 1.15 to 9.10 +/- 1.23, P =
      .016). CONCLUSIONS: SH patients exhibit a prothrombotic status, which is reverted
      by a 6-month L-T4 treatment.

PMID- 25955228
TI  - Kinetics of B-type natriuretic peptide plasma levels in patients with left-sided
      breast cancer treated with radiation therapy: Results after one-year follow-up.
AB  - PURPOSE: To analyze temporal changes of B-type natriuretic peptide (BNP) used as
      index of heart remodeling in left-sided breast cancer patients after radiotherapy
      (RT) and its relationship with dosimetric parameters. METHODS AND MATERIALS: BNP
      and dose-volume parameters for heart and ventricle were collected in 59 patients
      (median age 58.0 years) during a 1-year follow-up. Biochemical measurements were
      performed before the RT treatment (T0), at 15 days during RT (T(15day)), at the
      end of RT (T(endRT)), and then at 1, 3, 6, 9, 12 months (T1, T3, T6, T9 and T12).
      A logistical regression analysis was performed to identify demographic
      characteristics, dosimetric variables and risk factors associated with increased
      values of BNP. RESULTS: The ratio between the BNP value at T12 and the BNP value
      at T0 (BNP(T12)/BNP(T0)) increased significantly (p < 0.01). A significant
      association was found between the variation of BNP values after 1 year and the
      isodose received by 50% of the volume (D50% [Gy]) both to the heart (p = 0.03)
      and ventricle (p = 0.04). CONCLUSIONS: BNP plasma levels could provide additional
      information about subclinical RT-induced cardiotoxicity earlier than traditional
      ecocardiographic data.

PMID- 25955229
TI  - Proposed genitalia contouring guidelines in anal cancer intensity-modulated
      radiotherapy.
AB  - OBJECTIVE: Intensity-modulated radiotherapy (IMRT) for anal canal carcinoma (ACC)
      is associated with favourable toxicity outcomes. Side effects include sexual
      dysfunction, skin desquamation, pain and fibrosis to perineum and genitalia
      region. The genitalia are situated anterior to the primary ACC between two
      inguinal regions providing a challenging structure to avoid. Techniques improving
      outcomes require robust, consistent genitalia contouring to ensure
      standardization and production of fully optimized IMRT plans. Official
      recommendations for genitalia contouring are lacking. We describe a potential
      genitalia contouring atlas for ACC radiotherapy. METHODS: Following a review of
      genitalia CT anatomy, a contouring atlas was generated for male and female
      patients positioned prone and supine. Particular attention was paid to the
      reproducibility of the genitalia contour in all planes. RESULTS: Male and female
      genitalia positioned prone and supine are described and represented visually
      through a contouring atlas. Contoured areas in males include penis and scrotum,
      and in females include clitoris, labia majora and minora. The muscles, bone,
      prostate, vagina, cervix and uterus should be excluded. The genitalia contour
      extends laterally to inguinal creases and includes areas of fat and skin anterior
      to the symphysis pubis for both genders. CONCLUSION: This atlas provides
      descriptive and visual guidance enabling more consistent genitalia delineation
      for both genders when prone and supine. The atlas can be used for other sites
      requiring radiotherapy planning. ADVANCES IN KNOWLEDGE: This atlas presents
      visual contouring guidance for genitalia in ACC radiotherapy for the first time.
      Contouring methods provide reproducible genitalia contours that allow the
      provision of accurate dose toxicity data in future studies.

PMID- 25955230
TI  - Radiotherapy for non-malignant disorders: state of the art and update of the
      evidence-based practice guidelines.
AB  - Every year in Germany about 50,000 patients are referred and treated by
      radiotherapy (RT) for "non-malignant disorders". This highly successful treatment
      is applied only for specific indications such as preservation or recovery of the
      quality of life by means of pain reduction or resolution and/or an improvement of
      formerly impaired physical body function owing to specific disease-related
      symptoms. Since 1995, German radiation oncologists have treated non-malignant
      disorders according to national consensus guidelines; these guidelines were
      updated and further developed over 3 years by implementation of a systematic
      consensus process to achieve national upgraded and accepted S2e clinical practice
      guidelines. Throughout this process, international standards of evaluation were
      implemented. This review summarizes most of the generally accepted indications
      for the application of RT for non-malignant diseases and presents the special
      treatment concepts. The following disease groups are addressed: painful
      degenerative skeletal disorders, hyperproliferative disorders and symptomatic
      functional disorders. These state of the art guidelines may serve as a platform
      for daily clinical work; they provide a new starting point for quality
      assessment, future clinical research, including the design of prospective
      clinical trials, and outcome research in the underrepresented and less
      appreciated field of RT for non-malignant disorders.

PMID- 25955231
TI  - Image-guided radiotherapy and motion management in lung cancer.
AB  - In this review, image guidance and motion management in radiotherapy for lung
      cancer is discussed. Motion characteristics of lung tumours and image guidance
      techniques to obtain motion information are elaborated. Possibilities for
      management of image guidance and motion in the various steps of the treatment
      chain are explained, including imaging techniques and beam delivery techniques.
      Clinical studies using different motion management techniques are reviewed, and
      finally future directions for image guidance and motion management are outlined. 

PMID- 25955233
TI  - Are you a disruptor and is anyone paying attention?

PMID- 25955232
TI  - Inhibiting tumor necrosis factor-alpha signaling attenuates postoperative
      cognitive dysfunction in aged rats.
AB  - Postoperative cognitive dysfunction (POCD), commonly observed in elderly
      patients, is characterized by impaired concentration, memory and learning
      following surgery, and may persist for a long duration or progress into serious
      central nervous system diseases. It has been demonstrated neuroinflammation
      caused by surgery is involved in the development of POCD. However, the detailed
      molecular mechanism remains to be fully elucidated. The present study aimed to
      reveal the role of tumor necrosis factor (TNF)-alpha in the development of POCD
      in aged rats. Laparotomy was performed to mimic human abdominal surgery in the
      aged rats. Following surgery, the memory and learning functions were impaired,
      with significant upregulation of pro-inflammatory cytokines, including TNF-alpha,
      interleukin (IL)-1beta, IL-4 and IL-6 in the hippocampal tissues. However,
      intracisternal administration of the TNF-alpha receptor antagonist, R-7050,
      during surgery attenuated these defects in cognitive function and inhibited the
      production of the pro-inflammatory cytokines in the hippocampal tissues.
      Furthermore, intracisternal administration of R-7050 inhibited the activation of
      the downstream nuclear factor-kappaB and mitogen-activated protein kinase
      signaling pathway in the hippocampal tissues. Therefore, the results of the
      present study suggested a key role of the TNF-alpha-mediated signaling pathway in
      the development of POCD.

PMID- 25955234
TI  - Preparation of Polymeric Prodrug Paclitaxel-Poly(lactic acid)-b-Polyisobutylene
      and Its Application in Coatings of a Drug Eluting Stent.
AB  - To develop a novel biodegradable and quite adhesive coating material for
      fabricating a paclitaxel (PTX)-containing eluting stent, herein, we report two
      kinds of drug eluting stent (DES) materials. One of them is a prodrug, PTX end
      capped poly(lactic acid)-b-polyisobutylene (PTX-PLA-b-PIB) diblock copolymer,
      which possesses favorable biodegradability and biocompatibility. The other is a
      mixture of PIB-b-PLA diblock copolymer and PTX. PIB-b-PLA was synthesized via the
      ring-opening polymerization (ROP) using hydroxyl-terminated polyisobutylene (PIB
      OH) as the initiator, while the PTX-PLA-b-PIB prodrug was prepared through a
      combination of ROP and Cu(I)-catalyzed azide-alkyne cycloaddition "click"
      reaction. The chemical structures and compositions as well as the molecular
      weights and molecular weight distributions of these copolymers have been fully
      characterized by (1)H nuclear magnetic resonance, Fourier transform infrared, and
      gel permeation chromatography measurements. The thermal degradation behavior and
      glass transition temperature (Tg) of the copolymers were studied by
      thermogravimetric analysis and differential scanning calorimetry, respectively.
      The solutions of PTX-PLA-b-PIB and the PIB-b-PLA/PTX mixture were separately
      coated onto the bare metal stents to form the PTX-containing DES. Subsequently,
      the surface structures and morphologies of the bare stent and DES were studied by
      atomic force microscopy and scanning electron microscopy, respectively. The in
      vitro release of PTX from these stents was conducted in a buffer medium (PBS 7.4)
      at 37  degrees C. The results showed that the coating formed by a blend of PTX
      PLA-b-PIB, PIB-b-PLA, and PTX yielded a release that was better sustained than
      those of the individual PTX-PLA-b-PIB prodrug or PIB-b-PLA/PTX mixture. MTT
      assays demonstrated that the stent coated with PTX-PLA-b-PIB displayed a
      cytotoxicity lower than that of the PIB-b-PLA/PTX mixed layer, and the
      biocompatibility of coatings can be effectively improved by the prodrug. 

PMID- 25955235
TI  - A Cyst You Can't Miss: A Rare Presentation of an Orbital Apocrine Hidrocystoma.
AB  - Apocrine hidrocystomas are benign cystic lesions derived from the sweat glands of
      Moll and seldom found in the orbit. The authors present a case of a 41-year-old
      healthy man, with no prior medical history, referred for a painless enlarging
      mass, medial to his right upper eyelid for the past 3 months. Computed tomography
      showed a well-defined cystic lesion localized in the supero-medial anterior
      orbit. Following complete excision of the lesion, histopathology revealed an
      apocrine hidrocystoma. Although rare, apocrine hidrocystomas should be considered
      in the differential diagnosis for cystic mass of the orbit at any age group. 

PMID- 25955236
TI  - Leupaxin is expressed in mammary carcinoma and acts as a transcriptional
      activator of the estrogen receptor alpha.
AB  - Leupaxin belongs to the group of paxillin proteins and was reported to play a
      major role in the invasion and migration of prostate cancer cells. In the present
      study we were able to show by using a cDNA cancer profiling array that leupaxin
      is upregulated in breast and endometrial cancer, whereas downregulation of
      leupaxin was observed in lung cancer. In addition, immunohistochemical studies
      using a leupaxin-specific antibody on human breast cancer specimens (n=127)
      revealed that leupaxin is expressed mainly in invasive ductal carcinomas and
      ductal carcinoma in situ (40 and 49% respectively), and only in a minority of
      lobular mammary carcinomas. To further investigate the role of leupaxin in the
      progression of breast cancer the expression of leupaxin was analysed in six
      breast cancer cell lines. The estrogen receptor alpha (ERalpha)-positive HCC70
      and the ERalpha-negative MDA-MB-231 cells showed leupaxin expression on the RNA
      and protein level. Leupaxin localizes in these mammary carcinoma cells at focal
      adhesion sites and shuttles between membrane and nucleus via its LD4 motif as
      major nuclear export signal. Interaction partners of leupaxin in the nucleus
      represent the estrogen receptors ERalpha and ERbeta. Both ERalpha and ERbeta bind
      to the LIM domains of leupaxin via their AF-1/DNA binding domains. Furthermore,
      leupaxin is able to induce transcriptional activity of ERalpha independent of the
      presence of estradiol. The specific downregulation of leupaxin expression using
      siRNAs in mammary carcinoma cells resulted in reduced migratory capability and
      diminished invasiveness whereas no effect on proliferation was observed.
      Collectively, these results show that leupaxin has particular influence on the
      progression and invasion of breast cancer cells and may therefore represent an
      interesting candidate protein for diagnosis and therapeutic interventions.

PMID- 25955237
TI  - Discrimination of Isomeric Carbohydrates as the Electron Transfer Products of
      Group II Cation Adducts by Ion Mobility Spectrometry and Tandem Mass
      Spectrometry.
AB  - The rapid and unambiguous distinction of isomeric carbohydrate structures
      persists as a tremendous analytical challenge. This paper reports the first
      exploitation of carbohydrate/metal ion interactions in concert with gas-phase ion
      chemistry to improve discrimination of oligosaccharide isomers by both ion
      mobility spectrometry and tandem mass spectrometry. This is demonstrated for two
      isomeric pentasaccharides and two isomeric hexasaccharides, each studied in an
      underivatized form as their calcium ion adducts, barium ion adducts, and gas
      phase electron transfer products thereof. With appropriate selection of the
      charge carrier, transfer of a single electron to the carbohydrate metal ion
      adducts resulted in isomer-distinguishing shifts in their ion/neutral collision
      cross sections and the appearance of unique features in their vibrational
      activation/dissociation spectra. These findings suggest novel and elegant gas
      phase strategies for rapid differentiation of isomeric oligosaccharides. 

PMID- 25955238
TI  - Heterogeneous Degradation of Organic Pollutants by Persulfate Activated by CuO
      Fe3O4: Mechanism, Stability, and Effects of pH and Bicarbonate Ions.
AB  - Magnetic CuO-Fe3O4 composite was fabricated by a simple hydrothermal method and
      characterized as a heterogeneous catalyst for phenol degradation. The effects of
      pH and bicarbonate ions on catalytic activity were extensively evaluated in view
      of the practical applications. The results indicated that an increase of solution
      pH and the presence of bicarbonate ions were beneficial for the removal of phenol
      in the CuO-Fe3O4 coupled with persulfate (PS) process. Almost 100% mineralization
      of 0.1 mM phenol can be achieved in 120 min by using 0.3 g/L CuO-Fe3O4 and 5.0 mM
      PS at pH 11.0 or in the presence of 3.0 mM bicarbonate. The positive effect of
      bicarbonate ion is probably due to the suppression of copper leaching as well as
      the formation of Cu(III). The reuse of catalyst at pH0 11.0 and 5.6 showed that
      the catalyst remains a high level of stability at alkaline condition (e.g., pH0
      11.0). On the basis of the characterization of catalyst, the results of metal
      leaching and EPR studies, it is suggested that phenol is mainly destroyed by the
      surface-adsorbed radicals and Cu(III) resulting from the reaction between PS and
      Cu(II) on the catalyst. Taking into account the widespread presence of
      bicarbonate ions in waste streams, the CuO-Fe3O4/PS system may provide some new
      insights for contaminant removal from wastewater. 

PMID- 25955240
TI  - RE: J Altern Complement Med, 20(6):452-460.

PMID- 25955239
TI  - Combination therapy of traditional Chinese medicine and Western medicine to treat
      refractory polymyositis: a case report.
AB  - OBJECTIVE: To illustrate the potential for clinical improvement and regimen
      decrement in treating a patient with a refractory case of polymyositis (PM) with
      a combination of Western medicine and traditional Chinese medicine (TCM).
      INTERVENTIONS AND OUTCOME MEASURES: A 40-year-old man diagnosed with steroid
      resistant PM in January 2011 demonstrated a poor response to immunosuppressants.
      Complementary TCM treatments were applied to treat his weakness at a clinic
      integrating TCM and rheumatology in February 2012. He was treated with herbal
      formula powders named "Bu-Zhong-Yi-Qi-Tang" and "Si-Jun-Zi-Tan." Within 1 month
      of treatment, the patient seemed to show significant improvement in the grade of
      disability. Daily doses of methotrexate and methylprednisolone were tapered to
      25% and 95.8% after TCM treatments, respectively. Creatine phosphokinase also
      decreased from 6655 to 718 U/L until December 2013. CONCLUSIONS: In our
      experience, weakness related to PM can be improved by invigorating the spleen-Qi
      with TCM treatments. This might indicate that TCM treatments can not only play a
      role in symptom control but also accelerate steroid tapping for refractory cases.
      Long-term follow-up and future experimental studies are warranted to examine the
      efficacy and explore the mechanism of TCM treatments for PM.

PMID- 25955241
TI  - 3,3'-Diindolylmethane inhibits VEGF expression through the HIF-1alpha and NF
      kappaB pathways in human retinal pigment epithelial cells under chemical hypoxic
      conditions.
AB  - Oxidative stress in the retinal pigment epithelium (RPE) can lead to the
      pathological causes of age-related macular degeneration (AMD). Hypoxia induces
      oxidative damage in retinal pigment epithelial cells (RPE cells). In this study,
      we investigated the capacity of 3,3'-diindolylmethane (DIM) to reduce the
      expression of vascular endothelial growth factor (VEGF) under hypoxic conditions,
      as well as the molecular mechanisms involved. Human RPE cells (ARPE-19 cells)
      were treated with cobalt chloride (CoCl2, 200 uM) and/or DIM (10 and 20 uM). The
      production of VEGF was measured by enzyme-linked immunosorbent assay. The
      translocation of hypoxia-inducible factor-1alpha (HIF-1alpha) and nuclear factor
      kappaB (NF-kappaB) was determined by western blot analysis. The binding activity
      of HIF-1alpha and NF-kappaB was analyzed by electrophoretic mobility shift assay.
      The phosphorylation levels of mitogen-activated protein kinases (MAPKs) were
      measured by western blot analysis. The levels of mitochondrial reactive oxygen
      species (ROS) were detected by fluorescence microplate assay. The results
      revealed that DIM significantly attenuated the CoCl2-induced expression of VEGF
      in the ARPE-19 cells. The CoCl2-induced translocation and activation of HIF
      1alpha and NF-kappaB were also attenuated by treatment with DIM. In addition, DIM
      inhibited the CoCl2-induced activation of p38 MAPK in the ARPE-19 cells. Pre
      treatment with YCG063, a mitochondrial ROS inhibitor, led to the downregulation
      of the CoCl2-induced production of VEGF by suppressing HIF-1alpha and NF-kappaB
      activity. Taken together, the findings of our study demonstrate that DIM inhibits
      the CoCl2-induced production of VEGF by suppressing mitochondrial ROS production,
      thus attenuating the activation of HIF-1alpha and p38 MAPK/NF-kappaB.

PMID- 25955242
TI  - Correction: Sustained action of developmental ethanol exposure on the cortisol
      response to stress in zebrafish larvae and adults.

PMID- 25955243
TI  - Poor prospects for avian biodiversity in Amazonian oil palm.
AB  - Expansion of oil palm plantations across the humid tropics has precipitated
      massive loss of tropical forest habitats and their associated speciose biotas.
      Oil palm plantation monocultures have been identified as an emerging threat to
      Amazonian biodiversity, but there are no quantitative studies exploring the
      impact of these plantations on the biome's biota. Understanding these impacts is
      extremely important given the rapid projected expansion of oil palm cultivation
      in the basin. Here we investigate the biodiversity value of oil palm plantations
      in comparison with other dominant regional land-uses in Eastern Amazonia. We
      carried out bird surveys in oil palm plantations of varying ages, primary and
      secondary forests, and cattle pastures. We found that oil palm plantations
      retained impoverished avian communities with a similar species composition to
      pastures and agrarian land-uses and did not offer habitat for most forest
      associated species, including restricted range species and species of
      conservation concern. On the other hand, the forests that the oil palm companies
      are legally obliged to protect hosted a relatively species-rich community
      including several globally-threatened bird species. We consider oil palm to be no
      less detrimental to regional biodiversity than other agricultural land-uses and
      that political pressure exerted by large landowners to allow oil palm to count as
      a substitute for native forest vegetation in private landholdings with forest
      restoration deficits would have dire consequences for regional biodiversity. 

PMID- 25955244
TI  - Correction: Evidence for distinct coastal and offshore communities of bottlenose
      dolphins in the North East Atlantic.

PMID- 25955245
TI  - Antiarrhythmic Effects of Dantrolene in Patients with Catecholaminergic
      Polymorphic Ventricular Tachycardia and Replication of the Responses Using iPSC
      Models.
AB  - Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a highly
      malignant inherited arrhythmogenic disorder. Type 1 CPVT (CPVT1) is caused by
      cardiac ryanodine receptor (RyR2) gene mutations resulting in abnormal calcium
      release from sarcoplasmic reticulum. Dantrolene, an inhibitor of sarcoplasmic
      Ca(2+) release, has been shown to rescue this abnormal Ca(2+) release in vitro.
      We assessed the antiarrhythmic efficacy of dantrolene in six patients carrying
      various RyR2 mutations causing CPVT. The patients underwent exercise stress test
      before and after dantrolene infusion. Dantrolene reduced the number of premature
      ventricular complexes (PVCs) on average by 74% (range 33-97) in four patients
      with N-terminal or central mutations in the cytosolic region of the RyR2 protein,
      while dantrolene had no effect in two patients with mutations in or near the
      transmembrane domain. Induced pluripotent stem cells (iPSCs) were generated from
      all the patients and differentiated into spontaneously beating cardiomyocytes
      (CMs). The antiarrhythmic effect of dantrolene was studied in CMs after
      adrenaline stimulation by Ca(2+) imaging. In iPSC derived CMs with RyR2 mutations
      in the N-terminal or central region, dantrolene suppressed the Ca(2+) cycling
      abnormalities in 80% (range 65-97) of cells while with mutations in or near the
      transmembrane domain only in 23 or 32% of cells. In conclusion, we demonstrate
      that dantrolene given intravenously shows antiarrhythmic effects in a portion of
      CPVT1 patients and that iPSC derived CM models replicate these individual drug
      responses. These findings illustrate the potential of iPSC models to
      individualize drug therapy of inherited diseases.Trial Registration: EudraCT
      Clinical Trial Registry 2012-005292-14.

PMID- 25955248
TI  - Territoriality of giant otter groups in an area with seasonal flooding.
AB  - Territoriality carries costs and benefits, which are commonly affected by the
      spatial and temporal abundance and predictability of food, and by intruder
      pressure. Giant otters (Pteronura brasiliensis) live in groups that defend
      territories along river channels during the dry season using chemical signals,
      loud vocalizations and agonistic encounters. However, little is known about the
      territoriality of giant otters during the rainy season, when groups leave their
      dry season territories and follow fish dispersing into flooded areas. The
      objective of this study was to analyze long-term territoriality of giant otter
      groups in a seasonal environment. The linear extensions of the territories of 10
      giant otter groups were determined based on locations of active dens, latrines
      and scent marks in each season. Some groups overlapped the limits of neighboring
      territories. The total territory extent of giant otters was correlated with group
      size in both seasons. The extent of exclusive territories of giant otter groups
      was negatively related to the number of adults present in adjacent groups.
      Territory fidelity ranged from 0 to 100% between seasons. Some groups maintained
      their territory for long periods, which demanded constant effort in marking and
      re-establishing their territories during the wet season. These results indicate
      that the defense capacity of groups had an important role in the maintenance of
      giant otter territories across seasons, which may also affect the reproductive
      success of alpha pairs. 

PMID- 25955246
TI  - Characterization of early disease status in treatment-naive male paediatric
      patients with Fabry disease enrolled in a randomized clinical trial.
AB  - TRIAL DESIGN: This analysis characterizes the degree of early organ involvement
      in a cohort of oligo-symptomatic untreated young patients with Fabry disease
      enrolled in an ongoing randomized, open-label, parallel-group, phase 3B clinical
      trial. METHODS: Males aged 5-18 years with complete alpha-galactosidase A
      deficiency, without symptoms of major organ damage, were enrolled in a phase 3B
      trial evaluating two doses of agalsidase beta. Baseline disease characteristics
      of 31 eligible patients (median age 12 years) were studied, including cellular
      globotriaosylceramide (GL-3) accumulation in skin (n = 31) and kidney biopsy (n =
      6; median age 15 years; range 13-17 years), renal function, and glycolipid levels
      (plasma, urine). RESULTS: Plasma and urinary GL-3 levels were abnormal in 25 of
      30 and 31 of 31 patients, respectively. Plasma lyso-GL-3 was elevated in all
      patients. GL-3 accumulation was documented in superficial skin capillary
      endothelial cells (23/31 patients) and deep vessel endothelial cells (23/29
      patients). The mean glomerular filtration rate (GFR), measured by plasma
      disappearance of iohexol, was 118.1 mL/min/1.73 m(2) (range 90.4-161.0
      mL/min/1.73 m(2)) and the median urinary albumin/creatinine ratio was 10 mg/g
      (range 4.0-27.0 mg/g). On electron microscopy, renal biopsy revealed GL-3
      accumulation in all glomerular cell types (podocytes and parietal, endothelial,
      and mesangial cells), as well as in peritubular capillary and non-capillary
      endothelial, interstitial, vascular smooth muscle, and distal tubules/collecting
      duct cells. Lesions indicative of early Fabry arteriopathy and segmental
      effacement of podocyte foot processes were found in all 6 patients. CONCLUSIONS:
      These data reveal that in this small cohort of children with Fabry disease,
      histological evidence of GL-3 accumulation, and cellular and vascular injury are
      present in renal tissues at very early stages of the disease, and are noted
      before onset of microalbuminuria and development of clinically significant renal
      events (e.g. reduced GFR). These data give additional support to the
      consideration of early initiation of enzyme replacement therapy, potentially
      improving long-term outcome. TRIAL REGISTRATION: ClinicalTrials.gov NCT00701415.

PMID- 25955247
TI  - Differences in Hematological Traits between High- and Low-Altitude Lizards (Genus
      Phrynocephalus).
AB  - Phrynocephalus erythrurus (Lacertilia: Agamidae) is considered to be the highest
      living reptile in the world (about 4500-5000 m above sea level), whereas
      Phrynocephalus przewalskii inhabits low altitudes (about 1000-1500 m above sea
      level). Here, we report the differences in hematological traits between these two
      different Phrynocephalus species. Compared with P. przewalskii, the results
      indicated that P. erythrurus own higher oxygen carrying capacity by increasing
      red blood cell count (RBC), hemoglobin concentration ([Hb]) and hematocrit (Hct)
      and these elevations could promote oxygen carrying capacity without disadvantage
      of high viscosity. The lower partial pressure of oxygen in arterial blood (PaO2)
      of P. erythrurus did not cause the secondary alkalosis, which may be attributed
      to an efficient pulmonary system for oxygen (O2) loading. The elevated blood-O2
      affinity in P. erythrurus may be achieved by increasing intrinsic O2 affinity of
      isoHbs and balancing the independent effects of potential heterotropic ligands.
      We detected one alpha-globin gene and three beta-globin genes with 1 and 33 amino
      acid substitutions between these two species, respectively. Molecular dynamics
      simulation results showed that amino acids substitutions in beta-globin chains
      could lead to the elimination of hydrogen bonds in T-state Hb models of P.
      erythrurus. Based on the present data, we suggest that P. erythrurus have evolved
      an efficient oxygen transport system under the unremitting hypobaric hypoxia. 

PMID- 25955249
TI  - Structural Conversion of Abeta17-42 Peptides from Disordered Oligomers to U-Shape
      Protofilaments via Multiple Kinetic Pathways.
AB  - Discovering the mechanisms by which proteins aggregate into fibrils is an
      essential first step in understanding the molecular level processes underlying
      neurodegenerative diseases such as Alzheimer's and Parkinson's. The goal of this
      work is to provide insights into the structural changes that characterize the
      kinetic pathways by which amyloid-beta peptides convert from monomers to
      oligomers to fibrils. By applying discontinuous molecular dynamics simulations to
      PRIME20, a force field designed to capture the chemical and physical aspects of
      protein aggregation, we have been able to trace out the entire aggregation
      process for a system containing 8 Abeta17-42 peptides. We uncovered two
      fibrillization mechanisms that govern the structural conversion of Abeta17-42
      peptides from disordered oligomers into protofilaments. The first mechanism is
      monomeric conversion templated by a U-shape oligomeric nucleus into U-shape
      protofilament. The second mechanism involves a long-lived and on-pathway
      metastable oligomer with S-shape chains, having a C-terminal turn, en route to
      the final U-shape protofilament. Oligomers with this C-terminal turn have been
      regarded in recent experiments as a major contributing element to cell toxicity
      in Alzheimer's disease. The internal structures of the U-shape protofilaments
      from our PRIME20/DMD simulation agree well with those from solid state NMR
      experiments. The approach presented here offers a simple molecular-level
      framework to describe protein aggregation in general and to visualize the kinetic
      evolution of a putative toxic element in Alzheimer's disease in particular. 

PMID- 25955250
TI  - Toll-Like Receptor 9 Alternatively Spliced Isoform Negatively Regulates TLR9
      Signaling in Teleost Fish.
AB  - Toll-like receptor 9 (TLR9) recognizes and binds unmethylated CpG motifs in DNA,
      which are found in the genomes of bacteria and DNA viruses. In fish, Tlr9 is
      highly diverse, with the number of introns ranging from 0 to 4. A fish Tlr9 gene
      containing two introns has been reported to express two alternatively spliced
      isoforms, namely gTLR9A (full-length) and gTLR9B (with a truncated C'-terminal
      signal transducing domain), whose regulation and function remain unclear. Here,
      we report a unique regulatory mechanism of gTLR9 signaling in orange-spotted
      grouper (Epinephelus coioides), whose gTlr9 sequence also contains two introns.
      We demonstrated that the grouper gTlr9 gene indeed has the capacity to produce
      two gTLR9 isoforms via alternative RNA splicing. We found that gTLR9B could
      function as a negative regulator to suppress gTLR9 signaling as demonstrated by
      the suppression of downstream gene expression. Following stimulation with CpG
      oligodeoxynucleotide (ODN), gTLR9A and gTLR9B were observed to translocate into
      endosomes and co-localize with ODN and the adaptor protein gMyD88. Both gTLR9A
      and gTLR9B could interact with gMyD88; however, gTLR9B could not interact with
      downstream IRAK4 and TRAF6. Further analysis of the expression profile of gTlr9A
      and gTlr9B upon immune-stimulation revealed that the two isoforms were
      differentially regulated in a time-dependent manner. Overall, these data suggest
      that fish TLR9B functions as a negative regulator, and that its temporal
      expression is mediated by alternative RNA splicing. This has not been observed in
      mammalian TLR9s and might have been acquired relatively recently in the evolution
      of fish. 

PMID- 25955251
TI  - Dual or triple therapy in patients with atrial fibrillation and drug-eluting
      stents?

PMID- 25955252
TI  - Effects of Computer Navigation versus Conventional Total Knee Arthroplasty on
      Endothelial Damage Marker Levels: A Prospective Comparative Study.
AB  - Total knee arthroplasty (TKA) inevitably perturbs the femoral medullary canal,
      which increases blood loss or morbidities associated with marrow embolization
      postoperatively. Computer navigation TKA reportedly minimizes medullary
      disturbance to alleviate perioperative blood loss. We performed a prospective
      comparative study, enrolling 87 patients with osteoarthritic knees from March
      2011 to December 2011 in our hospital. The patients were separated into two
      groups, according to the surgeon they visited. Fifty-four patients underwent
      computer navigation TKAs and 33 had conventional TKAs. Levels of cell adhesion
      molecules (CAMs), including intercellular adhesion molecule-1 (ICAM-1), vascular
      cell adhesion molecule-1 (VCAM-1), and platelet endothelial cellular adhesion
      molecule-1 (PECAM-1) in sera and hemovac drainage were measured by ELISA before
      and 24 hours after the surgery. We showed that patients receiving computer
      navigation TKAs had less blood loss and lower CAMs in serum and hemovac drainage
      after the operation. Less postoperative elevation of serum ICAM-1 (p=0.022) and
      PECAM-1 (p=0.003) from the preoperative baseline after the surgery was also
      noted. This study provides molecular evidence for the differential extent in
      vascular injury between conventional and navigation TKAs and sheds light on the
      possible benefits of computer navigation TKAs. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT02206321.

PMID- 25955254
TI  - Phytophagous insects on native and non-native host plants: combining the
      community approach and the biogeographical approach.
AB  - During the past centuries, humans have introduced many plant species in areas
      where they do not naturally occur. Some of these species establish populations
      and in some cases become invasive, causing economic and ecological damage. Which
      factors determine the success of non-native plants is still incompletely
      understood, but the absence of natural enemies in the invaded area (Enemy Release
      Hypothesis; ERH) is one of the most popular explanations. One of the predictions
      of the ERH, a reduced herbivore load on non-native plants compared with native
      ones, has been repeatedly tested. However, many studies have either used a
      community approach (sampling from native and non-native species in the same
      community) or a biogeographical approach (sampling from the same plant species in
      areas where it is native and where it is non-native). Either method can sometimes
      lead to inconclusive results. To resolve this, we here add to the small number of
      studies that combine both approaches. We do so in a single study of insect
      herbivory on 47 woody plant species (trees, shrubs, and vines) in the Netherlands
      and Japan. We find higher herbivore diversity, higher herbivore load and more
      herbivory on native plants than on non-native plants, generating support for the
      enemy release hypothesis. 

PMID- 25955253
TI  - Autonomic effects of music in health and Crohn's disease: the impact of
      isochronicity, emotional valence, and tempo.
AB  - BACKGROUND: Music can evoke strong emotions and thus elicit significant autonomic
      nervous system (ANS) responses. However, previous studies investigating music
      evoked ANS effects produced inconsistent results. In particular, it is not clear
      (a) whether simply a musical tactus (without common emotional components of
      music) is sufficient to elicit ANS effects; (b) whether changes in the tempo of a
      musical piece contribute to the ANS effects; (c) whether emotional valence of
      music influences ANS effects; and (d) whether music-elicited ANS effects are
      comparable in healthy subjects and patients with Crohn's disease (CD, an
      inflammatory bowel disease suspected to be associated with autonomic
      dysfunction). METHODS: To address these issues, three experiments were conducted,
      with a total of n = 138 healthy subjects and n = 19 CD patients. Heart rate (HR),
      heart rate variability (HRV), and electrodermal activity (EDA) were recorded
      while participants listened to joyful pleasant music, isochronous tones, and
      unpleasant control stimuli. RESULTS: Compared to silence, both pleasant music and
      unpleasant control stimuli elicited an increase in HR and a decrease in a variety
      of HRV parameters. Surprisingly, similar ANS effects were elicited by isochronous
      tones (i.e., simply by a tactus). ANS effects did not differ between pleasant and
      unpleasant stimuli, and different tempi of the music did not entrain ANS
      activity. Finally, music-evoked ANS effects did not differ between healthy
      individuals and CD patients. CONCLUSIONS: The isochronous pulse of music (i.e.,
      the tactus) is a major factor of music-evoked ANS effects. These ANS effects are
      characterized by increased sympathetic activity. The emotional valence of a
      musical piece contributes surprisingly little to the ANS activity changes evoked
      by that piece.

PMID- 25955255
TI  - Glypican-3 targeted human heavy chain antibody as a drug carrier for
      hepatocellular carcinoma therapy.
AB  - Glypican-3 (GPC3) represents an attractive target for hepatocellular carcinoma
      (HCC) therapy because it is highly expressed in HCC but not in adult normal
      tissue. Recently, high affinity anti-GPC3 antibodies have been developed;
      however, full antibodies may not penetrate evenly into tumor parenchyma, reducing
      their effectiveness. In this study, we compared a whole IgG antibody, anti-GPC3
      YP7, with an anti-GPC3 human heavy chain antibody, HN3, with regard to their
      relative therapeutic effects. Both YP7 and HN3 bound to GPC3-positive A431/G1
      cells and were internalized by the cells by in vitro evaluation with (125)I- and
      (111)In-radiolabeling antibodies. In vivo biodistribution and tumor accumulation
      was performed with (111)In-labeled antibodies, and intratumoral microdistribution
      was evaluated using fluorescently labeled antibodies (IR700). HN3 showed similar
      high tumor accumulation but superior homogeneity within the tumor compared with
      YP7. Using the same IR700 conjugated antibodies photoimmunotherapy (PIT) was
      performed in vitro and in a tumor-bearing mouse model in vivo. PIT with IR700-HN3
      and IR700-YP7 demonstrated that comparable results could be achieved despite of
      low reaccumulation 24 h after the first NIR light exposure. These results
      indicated that a heavy-chain antibody, HN3, showed more favorable characteristics
      than YP7, a conventional IgG, as a therapeutic antibody platform for designing
      molecularly targeted agents against HCC. 

PMID- 25955256
TI  - Production of transgenic-cloned pigs expressing large quantities of recombinant
      human lysozyme in milk.
AB  - Human lysozyme is a natural non-specific immune factor in human milk that plays
      an important role in the defense of breastfed infants against pathogen infection.
      Although lysozyme is abundant in human milk, there is only trace quantities in
      pig milk. Here, we successfully generated transgenic cloned pigs with the
      expression vector pBAC-hLF-hLZ-Neo and their first generation hybrids (F1). The
      highest concentration of recombinant human lysozyme (rhLZ) with in vitro
      bioactivity was 2759.6 +/- 265.0 mg/L in the milk of F0 sows. Compared with wild
      type milk, rhLZ milk inhibited growth of Escherichia coli K88 during the
      exponential growth phase. Moreover, rhLZ in milk from transgenic sows was
      directly absorbed by the intestine of piglets with no observable anaphylactic
      reaction. Our strategy may provide a powerful tool for large-scale production of
      this important human protein in pigs to improve resistance to pathogen infection.

PMID- 25955257
TI  - Strategy of health information seeking among physicians, medical residents, and
      students after introducing digital library and information technology in teaching
      hospitals of Iran.
AB  - OBJECTIVES: It is important for physicians, medical students and health care
      organizations of developing countries to use reliable clinical information in
      order to deliver the best practice. Therefore, health sector of Iran endeavored
      to encourage physicians and medical students to integrate research findings into
      practice since 2005. Several educational interventions in the areas of
      information technology and databases were performed. Digital library was
      introduced in the teaching hospitals. The purpose of this study was to
      investigate whether these interventions increased the use of evidence-based
      health information resources among physicians, medical residents and students.
      METHODS: This descriptive study involved 315 physicians, assistants and medical
      students in affiliated hospitals of Semnan University of medical sciences in
      2013. RESULTS: A total 52.9% of physicians and 79.5% of medical residents and
      students always used patient data. 81.3% of physicians and 67.1% of medical
      residents and students reported using their own experiences, 26.5% of physicians
      and 16.9% of medical residents and students always used databases such as PubMed
      and MEDLINE for patient care. CONCLUSION: Our results revealed that in spite of
      providing educational and technical infrastructures for accomplishment of
      research utilization in medical education, the study subjects often identified
      and used what they regarded as reliable and relevant information from sources
      that do not truly represent the best evidence that is available.

PMID- 25955259
TI  - The Spectrum of Self-injurious Behavior.

PMID- 25955258
TI  - miR-139 and miR-200c regulate pancreatic cancer endothelial cell migration and
      angiogenesis.
AB  - Pancreatic cancer remains the fourth deathliest cancer worldwide with a 5-year
      survival rate of only 4%. The present study tested the hypothesis that
      dysregulated microRNA (miRNA) expression by pancreatic cancer endothelial cells
      (CECs) may regulate angiogenesis. Primary EC cultures were established from the
      pancreatic tumor and adjacent normal tissues of three pancreatic cancer patients.
      A miRNA microarray was used to identify miRNAs that were differentially
      expressed. The expression patterns of four highly expressed miRNAs in CECs were
      confirmed by qPCR analysis. The effects of dysregulated miRNA expression on CEC
      proliferation, migration and tube formation were determined after transfection
      with specific miRNA inhibitors. The expression of 14 miRNAs was increased by >20
      fold in the the CECs of all three pancreatic patients; the increased expression
      of miR-200c and miR-139 in CECs was confirmed. miR-1, mir-139 and miR-200c
      inhibitors significantly reduced CEC migration (all P<0.05), yet not
      proliferation. The average tube length and total loop number were also
      significantly decreased upon miR-139 and miR-200c inhibition in all three CEC
      cultures (all P<0.05). Upregulation of miR-139 and miR-200c expression may
      increase CEC migration and tube formation, which suggests that these miRNAs may
      regulate pancreatic tumor angiogenesis.

PMID- 25955260
TI  - Common factors affecting psychotherapy outcomes: some implications for teaching
      psychotherapy.
AB  - The number of psychotherapies classified as "empirically supported treatments"
      has increased significantly. As the number and scope of empirically supported
      treatments multiply, it has become impossible to train therapists in all of these
      specific modalities. Although the current Accreditation Council for Graduate
      Medical Education requirements for psychiatric residents follow an approach based
      on specific schools of psychotherapy (emphasizing competency in cognitive
      behavioral therapy, psychodynamic therapy, and supportive treatments), evidence
      suggests that we are failing even in these efforts. In developing a specialized
      Psychotherapy Scholars Track in the residency program at the University of
      Colorado School of Medicine, we opted to focus initially on teaching the common
      factors in psychotherapy that positively affect psychotherapy outcomes. This
      article reviews 6 such broad common factors. 

PMID- 25955261
TI  - Associations between components of metabolic syndrome and cognition in patients
      with schizophrenia.
AB  - The metabolic syndrome and cognitive dysfunctions are common in patients with
      schizophrenia, yet there is no general consensus concerning the effects of the
      components of the metabolic syndrome on various cognitive domains. The goal of
      this study was to investigate the relationship between components of the
      metabolic syndrome and cognition in patients with schizophrenia. Components of
      the metabolic syndrome and neurocognitive functioning were assessed in 68
      patients with schizophrenia. The Brief Assessment of Cognition in Schizophrenia
      (BACS) was used to assess neurocognition. Hyperglycemia and hypertension were the
      only components of the metabolic syndrome found to be associated with cognitive
      functioning. Patients with schizophrenia who were hypertensive showed cognitive
      impairments in 2 domains, with a negative association found between hypertension
      and verbal memory (P=0.047) and verbal fluency (P=0.007). Hyperglycemia was
      associated with higher scores on verbal memory (P=0.01) and verbal fluency
      (P<0.001). It appears that medical treatment of certain components of the
      metabolic syndrome could affect cognitive performance in patients with
      schizophrenia. 

PMID- 25955262
TI  - Differences between nonsuicidal self-injury and suicidal behavior in patients
      with eating disorders.
AB  - Although it has been reported that 25% to 50% of patients with eating disorders
      engage in self-harming behaviors (SHBs), including nonsuicidal self-injury (NSSI)
      and suicidal behavior (SB), no study has investigated the psychological
      mechanisms underlying these SHBs or any differences that may exist between NSSI
      and SB. This study involved 76 female patients with eating disorders who were
      treated at the Kyoto University Hospital between July and August, 2010, who
      answered questionnaires about SHBs, eating attitudes, tendency to dissociate, and
      attachment style. Some of the participants (22.4%) had other psychiatric
      disorders in addition to eating disorders, including borderline personality
      disorder, dissociative disorder, and posttraumatic stress disorder. Of the
      participants without comorbidity, 23.7% had engaged in SHBs in the past 3 months.
      Participants with comorbidity tended to dissociate significantly more than
      participants without comorbidity. Logistic regression indicated that, in all
      participants, NSSI in the past 3 months was related to the tendency to dissociate
      and having a higher body mass index, whereas preoccupied attachment style was
      potentially related to recent SB. Specifically, among the participants without
      comorbidity, a sense of ineffectiveness and poor interoceptive awareness were
      related to recent NSSI, and severity of binge-eating was related to SB. In
      contrast, a history of NSSI in the patients with eating disorders without
      comorbidity was related to a sense of ineffectiveness. The results of our study
      suggest that it may be important to help patients with eating disorders recover
      their own sense of effectiveness as a possible way to reduce SHBs. 

PMID- 25955263
TI  - Improvements in depression severity in hospitalized patients with and without
      borderline personality features.
AB  - INTRODUCTION: Patients with borderline personality disorder (BPD) often struggle
      with treatment-resistant depression. To date, few studies have specifically
      assessed the rate of improvement of depressive symptoms during an acute inpatient
      hospitalization in patients who screen positive for BPD compared with those who
      do not. METHODS: A sample of 245 psychiatric inpatients was divided into 2 groups
      on the basis of whether or not they tested positive on the McLean Screening
      Instrument for Borderline Personality Disorder (MSI-BPD). Hamilton Depression
      Rating Scale (Ham-D) scores were compared from admission to discharge. RESULTS:
      At admission, the MSI-BPD group (n=64) endorsed significantly more depressive
      symptoms than the MSI-BPD group (n=181), as measured by higher mean Ham-D scores
      (34.1 vs. 30.3, P=0.0002). Although both groups demonstrated improvements in Ham
      D scores by discharge, the MSI-BPD group showed a markedly more robust change
      (22.1 vs. 18.2, P=0.002). This effect remained significant using a propensity
      score model to account for differences in baseline characteristics between the 2
      groups (22.1 vs. 18.8, P=0.022). CONCLUSIONS: These findings suggest that
      patients who test positive on this BPD screening tool tend to be admitted in
      greater distress and to subsequently improve more robustly in the setting of an
      inpatient hospitalization. This finding lends support to the theory that the
      depressive symptoms associated with borderline personality pathology emerge in
      the context of interpersonal hypersensitivity and relationship instability and
      therefore that the holding environment of the hospital can result in rapid
      improvement.

PMID- 25955264
TI  - An open letter to early-career psychiatrists.
AB  - The author addresses early-career psychiatrists (ECPs) and graduating trainees
      about the challenges they will face in preserving the psychotherapeutic aspect of
      their professional identity during the coming years. Rapidly changing health care
      systems, high demand for services, conflicting paradigms for treatment,
      inadequate compensation for psychotherapy, disruptive third-party payers,
      bureaucratic demands, ECPs' own educational debts, and personal and family needs
      all present the potential for stressful internal conflicts and difficult choices.
      However, ECPs are a scarce commodity. They hold the power of decision about what
      they will and will not do, and they can be guided by the satisfaction of living
      out a truly integrated biopsychosocial identity. 

PMID- 25955265
TI  - Balancing patient care and confidentiality: considerations in obtaining
      collateral information.
AB  - Collateral information facilitates comprehensive mental health care and is
      consistent with recovery-oriented models of care. But providers are often faced
      with complex decisions about obtaining collateral information, particularly when
      patients do not consent to communication with third parties for information
      gathering. Such situations require a thoughtful balance of best clinical
      practices, legal and ethical responsibilities, and patient safety concerns. This
      column offers an overview of the clinical utility of collateral information as
      well as the ethical and legal regulations concerning confidentiality that guide
      the process of obtaining collateral information. The risk-benefit analysis
      process related to obtaining collateral information without patient permission is
      illustrated. Recommendations about clinical consultation and documentation that
      facilitate optimal and ethical patient care are offered. 

PMID- 25955266
TI  - Extended-release Methylphenidate Treatment and Outcomes in Comorbid Social
      Anxiety Disorder and Attention-deficit/Hyperactivity Disorder: 2 Case Reports.
AB  - Social anxiety disorder is frequently comorbid with attention
      deficit/hyperactivity disorder (ADHD). However, treatment recommendations are not
      clear in the presence of such comorbidity. A few studies in the literature have
      reported improvement in symptoms of both disorders with treatment specific for
      ADHD (ie, stimulants and atomoxetine). In this report, we present cases of 2
      adults with social anxiety disorder and ADHD who were treated with
      methylphenidate monotherapy. Both cases responded well in terms of not only their
      ADHD symptoms but also the social anxiety disorder symptoms. Methylphenidate was
      well tolerated with no significant side effects. More studies are needed to
      better establish the potential of ADHD medications to be effective for comorbid
      social anxiety disorder symptoms. 

PMID- 25955267
TI  - Clinical Utility of the 2 New Scales of the Health of the Nation Outcome Scales
      for Children and Adolescents (HoNOSCA): A Naturalistic, Prospective Study in a
      Psychiatric Unit for Adolescents.
AB  - OBJECTIVES: The goal of this study was to assess the clinical usefulness of the
      emotional symptoms (Emo) and externalizing problems (Ext) scales compared with
      the Total score on the Health of the Nation Outcome Scales for Children and
      Adolescents (HoNOSCA). METHODS: The HoNOSCA was rated at admission and discharge
      for 260 adolescent inpatients. The primary outcomes assessed were (a) the
      sensitivity of the 3 HoNOSCA scores to clinical improvement; and (b) the between
      diagnoses discriminative value of these scores. RESULTS: Analyses of variances [2
      (time: admission vs. discharge) * 5 (diagnostic groups)] revealed a main effect
      of time for the 3 scores, a main effect of the diagnostic group for the Total and
      Ext scores, and an interaction effect between time and diagnosis for the Emo
      score. A moderate correlation was observed between the change in Ext and Emo
      scores between admission and discharge. DISCUSSION: These 2 new scales of the
      HoNOSCA demonstrated good clinical utility and the ability to assess different
      aspects of clinical improvements. A significant discriminative value of both
      scores was observed. SIGNIFICANT OUTCOMES: The clinical utility of the 2 new
      scales on the HoNOSCA was established. These 2 new scales provided a sensitive
      measure of clinical outcome for assessing improvement between admission and
      discharge on a psychiatric inpatient unit for adolescents, regardless of
      diagnostic group, and captured additional information about clinical
      improvements. Adolescents with psychosis and conduct disorders presented with
      higher externalizing symptoms than those with other disorders, as rated on the
      HoNOSCA, at admission and discharge. The Emo score differentiated between
      clinical improvement in patients with psychosis versus eating disorders.
      LIMITATIONS: The sample in this study represented a homogeneous population of
      adolescent inpatients, so that further research is needed before these findings
      can be generalized to outpatients. In addition, the small number of patients in
      some diagnostic groups did not allow for their inclusion in some of the
      statistical analyses.

PMID- 25955269
TI  - Endoscopic-assisted Distal Biceps Footprint Repair.
AB  - Distal biceps tendon ruptures have been treated successfully with a variety of
      techniques; however, no current technique is able to restore the biceps to its
      native footprint on the ulnar surface of the radial tuberosity. We describe a
      technique, using an endobutton that better recreates the anatomic distal biceps
      footprint. This is likely to better restore absoloute and repetitive supination
      strength, which is not reliably achieved with current techniques. 

PMID- 25955270
TI  - A treatment algorithm for the management of distal triceps ruptures.
AB  - Rupture of the distal triceps brachii muscle is a relatively rare, but
      potentially troublesome injury. Recent literature has increased awareness of the
      injury and highlighted the importance of accurate diagnosis and prompt
      appropriate treatment of these injuries. The history, physical examination
      findings, and imaging studies are key to determine complete versus partial
      rupture of the distal triceps. We propose a treatment algorithm based on the
      chronicity of the injury and associated tendon quality. Such a guide can help
      surgeons navigate the most appropriate treatment and be equipped with the
      surgical tools to provide the best surgical result. 

PMID- 25955268
TI  - Tissue factor expressed by circulating cancer cell-derived microparticles
      drastically increases the incidence of deep vein thrombosis in mice.
AB  - BACKGROUND: The risk of thrombotic complications such as deep vein thrombosis
      (DVT) during tumor development is well known. Tumors release into the circulation
      procoagulant microparticles (MPs) that can participate in thrombus formation
      following vessel injury. The importance of this MP tissue factor (TF) in the
      initiation of cancer-associated DVT remains uncertain. OBJECTIVE: To investigate
      how pancreatic cancer MPs promote DVT in vivo. METHODS: We combined a DVT mouse
      model in which thrombosis is induced by flow restriction in the inferior vena
      cava with one of subcutaneous pancreatic cancer in C57BL/6J mice. We infused high
      TF and low-TF tumor MPs to determine the importance of TF in experimental cancer
      associated DVT. RESULTS: Both tumor-bearing mice and mice infused with tumor MPs
      subjected to 3 h of partial flow restriction developed an occlusive thrombus;
      fewer than one-third of the control mice did. We observed that MPs adhered to
      neutrophil extracellular traps (NETs), which are functionally important players
      during DVT, whereas neither P-selectin nor glycoprotein Ib were required for MP
      recruitment in DVT. The thrombotic phenotype induced by MP infusion was
      suppressed by hirudin, suggesting the importance of thrombin generation. TF
      carried by tumor MPs was essential to promote DVT, as mice infused with low-TF
      tumor MPs had less thrombosis than mice infused with high-TF tumor MPs.
      CONCLUSIONS: TF expressed on tumor MPs contributes to the increased incidence of
      cancer-associated venous thrombosis in mice in vivo. These MPs may adhere to NETs
      formed at the site of thrombosis.

PMID- 25955271
TI  - Dissection of C. elegans behavioral genetics in 3-D environments.
AB  - The nematode Caenorhabditis elegans is a widely used model for genetic dissection
      of animal behaviors. Despite extensive technical advances in imaging methods, it
      remains challenging to visualize and quantify C. elegans behaviors in three
      dimensional (3-D) natural environments. Here we developed an innovative 3-D
      imaging method that enables quantification of C. elegans behavior in 3-D
      environments. Furthermore, for the first time, we characterized 3-D-specific
      behavioral phenotypes of mutant worms that have defects in head movement or
      mechanosensation. This approach allowed us to reveal previously unknown functions
      of genes in behavioral regulation. We expect that our 3-D imaging method will
      facilitate new investigations into genetic basis of animal behaviors in natural 3
      D environments. 

PMID- 25955272
TI  - Decreased mRNA and protein expression of TWIST1 in myocardial tissue of fetuses
      with ventricular septal defects.
AB  - Ventricular septal defect (VSD) is the most common type of congenital heart
      disease (CHD). The single gene mutations or absences that contribute to VSD
      development are well established; however, the aim of the present study was to
      measure gene expression variation between VSDs and normal fetal myocardial
      tissue. TWIST1, an important tumor biomarker, is a basic helix-loop-helix
      transcription factor that regulates cell proliferation, migration and
      differentiation in embryonic development and transformed tumor cells. Although
      growing evidence demonstrates that TWIST1 participates in a variety of human
      neoplastic diseases, the role of TWIST1 in VSD has remained elusive. Twenty-six
      VSD fetal myocardial tissue samples and 12 normal samples at matched gestational
      weeks (22-28 weeks) were included in the present study. Using reverse
      transcription quantitative polymerase chain reaction (PCR) and real-time PCR, it
      was demonstrated that TWIST1 mRNA was reduced by almost two-fold in the VSD
      samples compared with the normal samples. Western blot analysis also revealed
      that TWIST1 expression was decreased by ~three-fold (P=0.001) in the VSD samples
      compared with that in the normal samples. Of note, five complete ventricular
      (also called functionally univentricular or single ventricular) septal ageneses
      were identified among the specimens. For the five complete ventricular septal
      agenesis samples, similar results to those for other VSD fetal myocardial tissues
      were obtained. In conclusion, the results of the present study showed that TWIST1
      mRNA and protein levels were reduced in VSDs. The present study was the first, to
      the best of our knowledge, to report that TWIST1 is not only a tumor biomarker,
      but may also be involved in the pathogenesis of VSD.

PMID- 25955273
TI  - What's in a Name? Does Population Health Have the Same Meaning for All
      Stakeholders?

PMID- 25955274
TI  - Ultra-fast data-mining hardware architecture based on stochastic computing.
AB  - Minimal hardware implementations able to cope with the processing of large
      amounts of data in reasonable times are highly desired in our information-driven
      society. In this work we review the application of stochastic computing to
      probabilistic-based pattern-recognition analysis of huge database sets. The
      proposed technique consists in the hardware implementation of a parallel
      architecture implementing a similarity search of data with respect to different
      pre-stored categories. We design pulse-based stochastic-logic blocks to obtain an
      efficient pattern recognition system. The proposed architecture speeds up the
      screening process of huge databases by a factor of 7 when compared to a
      conventional digital implementation using the same hardware area. 

PMID- 25955275
TI  - Fe3O4@ZIF-8: magnetically recoverable catalysts by loading Fe3O4 nanoparticles
      inside a zinc imidazolate framework.
AB  - A simple methodology for encapsulating ca. 10 nm-sized superparamagnetic Fe3O4
      nanoparticles in zeolitic imidazolate frameworks (ZIF-8) crystals was developed.
      The corresponding Fe3O4@ZIF-8 heterostructured material exhibits bifunctional
      properties with both high magnetization (Fe3O4) and high thermal stability, large
      specific surface, and catalytic properties (ZIF-8). The Fe3O4@ZIF-8 catalyst
      exhibits fair separation ability and reusability, which can be repeatedly applied
      for Knoevenagel condensations and Huisgen cycloadditions for at least ten
      successive cycles. 

PMID- 25955276
TI  - Unmeasured costs of haemophilia: the economic burden on families with children
      with haemophilia.
AB  - INTRODUCTION AND OBJECTIVES: Although economic evaluations of haemophilia-related
      care have highlighted both the health care payer and societal perspectives, the
      costs to families with children with haemophilia have not been examined. This
      study determined the costs incurred by families of children with haemophilia,
      attending a haemophilia treatment centre (HTC), servicing a large geographical
      area in Eastern Canada. METHODS: Families recorded all direct and indirect costs
      associated with haemophilia-related care for a year. Costs incurred to receive
      care at the HTC and local health care centres were compared. The relationship
      between distance to the HTC and costs was modelled using linear regression.
      RESULTS: Participants included 31/45 children (68%) from 27 families attending
      the HTC. Median age was 12 years (range: 0.5-17 years); 24/31 (77%) had severe
      haemophilia. The median distance to the HTC and local health care facility was
      230 km (range: 7-600 km) and 33.5 km (range: 2-400 km) respectively. Due to this
      difference in distance, 23/31 (74%) children do not attend the HTC for management
      of acute haemorrhage. The median annual total cost per family to attend the HTC
      is $775.93 (range: $200.00-$5741.00). The total cost to attend the HTC increases
      by $2.16 (95% CI 1.24-3.9) per kilometer from the HTC. The median total annual
      cost of haemophilia-related care per family is $1222.50 (range: $396.00
      $8037.00). CONCLUSION: Families incur high costs related to haemophilia care. The
      distance to the HTC is a barrier to care. Improving access to HTCs is paramount
      in improving haemophilia-related outcomes.

PMID- 25955277
TI  - Brugada syndrome, exercise, and exercise testing.
AB  - There are few data on the risk of exercise and the role of exercise stress
      testing in Brugada syndrome. We sought to address this deficiency using a
      systematic literature review. We identified 98 English-language articles possibly
      addressing exercise in Brugada syndrome by searching PubMed and Google Scholar
      from January 1990 through November 2013 using the keywords "Brugada syndrome,"
      "exercise," "exercise testing," and "syncope" alone and in combinations.
      Abstracts were reviewed, and those articles pertaining to Brugada syndrome and
      exercise were reviewed in full. We identified 18 articles reporting on Brugada
      syndrome and exercise. This pool included 2 large studies of 93 and 50 Brugada
      subjects undergoing exercise testing, plus 16 case reports. There were no reports
      of exercise-related sudden death, but there were 4 cases of syncope after
      exercise. We identified 166 Brugada patients who underwent exercise testing.
      During exercise testing, there were 2 reports of ventricular tachycardia and 1
      report of multiple ventricular extrasystoles. ST-segment elevation increased (ST
      augmentation) during the early recovery phase of exercise in 57% of patients.
      Exercise unmasked a Brugada electrocardiographic pattern in 5 patients. Exercise
      is associated with syncope and ST augmentation after exercise and may be helpful
      in unmasking Brugada syndrome. There are insufficient data on the risks of
      exercise in Brugada syndrome to make recommendations for exercise, but the
      observations that exercise can worsen the ST abnormalities in Brugada and produce
      ventricular arrhythmias suggest that patients with Brugada syndrome should be
      restricted from vigorous exercise. 

PMID- 25955278
TI  - Differential modulation of the N2 and P3 event-related potentials by response
      conflict and inhibition.
AB  - BACKGROUND: Developing reliable and specific neural markers of cognitive
      processes is essential to improve understanding of healthy and atypical brain
      function. Despite extensive research there remains uncertainty as to whether two
      electrophysiological markers of cognitive control, the N2 and P3, are better
      conceptualised as markers of response inhibition or response conflict. The
      present study aimed to directly compare the effects of response inhibition and
      response conflict on the N2 and P3 event-related potentials, within-subjects.
      METHOD: A novel hybrid go/no-go flanker task was performed by 19 healthy adults
      aged 18-25 years while EEG data were collected. The response congruence of a
      central target stimulus and 4 flanking stimuli was manipulated between trials to
      vary the degree of response conflict. Response inhibition was required on a
      proportion of trials. N2 amplitude was measured at two frontal electrode sites;
      P3 amplitude was measured at 4 midline electrode sites. RESULTS: N2 amplitude was
      greater on incongruent than congruent trials but was not enhanced by response
      inhibition when the stimulus array was congruent. P3 amplitude was greater on
      trials requiring response inhibition; this effect was more pronounced at frontal
      electrodes. P3 amplitude was also enhanced on incongruent compared with congruent
      trials. DISCUSSION: The findings support a role for N2 amplitude as a marker of
      response conflict and for the frontal shift of the P3 as a marker of response
      inhibition. This paradigm could be applied to clinical groups to help clarify the
      precise nature of impaired action control in disorders such as attention
      deficit/hyperactivity disorders (ADHD).

PMID- 25955279
TI  - Endothelin Receptor B2 (EDNRB2) Gene Is Associated with Spot Plumage Pattern in
      Domestic Ducks (Anas platyrhynchos).
AB  - Endothelin receptor B subtype 2 (EDNRB2) is a seven-transmembrane G-protein
      coupled receptor. In this study, we investigated EDNRB2 gene as a candidate gene
      for duck spot plumage pattern according to studies of chicken and Japanese quail.
      The entire coding region was cloned by the reverse transcription polymerase chain
      reaction (RT-PCR). Sequence analysis showed that duck EDNRB2 cDNA contained a
      1311 bp open reading frame and encoded a putative protein of 436 amino acids
      residues. The transcript shared 89%-90% identity with the counterparts in other
      avian species. A phylogenetic tree based on amino acid sequences showed that duck
      EDNRB2 was evolutionary conserved in avian clade. The entire coding region of
      EDNRB2 were sequenced in 20 spot and 20 non-spot ducks, and 13 SNPs were
      identified. Two of them (c.940G>A and c.995G>A) were non-synonymous
      substitutions, and were genotyped in 647 ducks representing non-spot and spot
      phenotypes. The c.995G>A mutation, which results in the amino acid substitution
      of Arg332His, was completely associated with the spot phenotype: all 152 spot
      ducks were carriers of the AA genotype and the other 495 individuals with non
      spot phenotype were carriers of GA or GG genotype, respectively. Segregation in
      17 GA*GG and 22 GA*GA testing combinations confirmed this association since the
      segregation ratios and genotypes of the offspring were in agreement with the
      hypothesis. In order to investigate the underlying mechanism of the spot
      phenotype, MITF gene was used as cell type marker of melanocyte progenitor cells
      while TYR and TYRP1 gene were used as cell type markers of mature melanocytes.
      Transcripts of MITF, TYR and TYRP1 gene with expected size were identified in all
      pigmented skin tissues while PCR products were not obtained from non-pigmented
      skin tissues. It was inferred that melanocytes are absent in non-pigmented skin
      tissues of spot ducks.

PMID- 25955280
TI  - A real-world study of the effect of timing of insulin initiation on outcomes in
      older medicare beneficiaries with type 2 diabetes mellitus.
AB  - OBJECTIVES: To compare clinical and economic outcomes of early insulin initiation
      with those of delayed initiation in older adults with type 2 diabetes mellitus
      (T2DM). DESIGN: Retrospective cohort study. SETTING: Humana Medicare Advantage
      health insurance plan. PARTICIPANTS: Older (>=65) Medicare beneficiaries with
      T2DM. MEASUREMENTS: Subjects were grouped according to number of classes of oral
      antidiabetes drugs (OADs) they had taken before initiation of insulin: one (early
      insulin initiators), two, or three or more (delayed insulin initiators). One-year
      follow-up outcomes included change in glycosylated hemoglobin (HbA1c), percentage
      of older adults with HbA1c less than 8.0%, hypoglycemic events, and total
      healthcare costs. RESULTS: Overall, 14,669 individuals were included in the
      analysis. Baseline and 1-year follow-up HbA1c levels were available for 4,028
      (27.5%) individuals. Insulin was initiated early in 32% and delayed in 20%. At
      follow-up, unadjusted reduction in HbA1c was 0.9+/-3.7% for the group with one
      OAD, 0.7+/-2.4% for those with two, and 0.5+/-3.6% for those with three or more.
      Early insulin initiation was associated with significantly greater reduction in
      HbA1c (0.4%; adjusted P<.001), 30% greater likelihood of achieving HbA1c less
      than 8.0% (adjusted odds ratio=1.30, 95% confidence interval=1.18-1.43), and no
      significant differences in total costs or hypoglycemia events (11.5% of early
      initiators vs 10.2% of delayed initiators; P=.32). CONCLUSION: This study
      suggests beneficial effects of early insulin initiation in older adults with T2DM
      who do not have adequate glycemic control, without increasing the risk of
      hypoglycemia or greater total direct healthcare costs.

PMID- 25955283
TI  - High fat diet-induced estrus cycle disruption: effects of Ficus asperifolia.
AB  - BACKGROUND: Ficus asperifolia (L) Hook. Ex Miq (Moraceae) fruits are used in
      Cameroonian traditional medicine to cure some cases of infertility in women. This
      study determines the mechanism of alleviating effect of the plant extracts on rat
      infertility induced by a high fat diet (HFD). METHODS: Obesity was reached by
      feeding female rats with a HFD for 10 weeks. Vaginal smear was observed daily for
      3 weeks after animals were obese. Then, 70 animals with abnormal estrus cyclicity
      were selected and partitioned into two sets of 35 animals. Each set was further
      divided into seven groups of five rats. These obese rats with disrupted estrus
      cyclicity were orally administered the aqueous and methanolic extracts (100 and
      500 mg/kg), distilled water (10 mL/kg), 5% Tween 80 (10 mL/kg) or lutenyl (0.8
      ug/kg) once a day for 1 week (set I) or 4 weeks (set II). Estrus cyclicity, body
      weight gain, hematocrit, lipid profile, ovarian, uterine and hepatic growth
      indices were determined at the end of each treatment. RESULTS: HFD increased the
      body weight of the animals by 27% and disrupted the estrus cyclicity by 98.44%.
      Aqueous extract (100 mg/kg) of F. asperifolia given for 1 week corrected 40% of
      the irregular estrus cycle and this percentage increased to 80% as the treatment
      progressed to 4 weeks. F. asperifolia-treated obese rats (mostly with the aqueous
      extract at 100 mg/kg) showed a significant decrease (p<0.001) in the total plasma
      cholesterol and low density lipoprotein (LDL) cholesterol level and a significant
      increase (p<0.001) in high density lipoprotein (HDL) cholesterol. F. asperifolia
      has bioactive agents that may maintain conducive conditions for reproduction in
      obese female rats. CONCLUSIONS: Our data support the anecdotal claims of F.
      asperifolia in folk medicine to cure some cases of infertility in women.

PMID- 25955284
TI  - Syzygium cumini seed extract ameliorates adenosine deaminase activity and
      biochemical parameters but does not alter insulin sensitivity and pancreas
      architecture in a short-term model of diabetes.
AB  - BACKGROUND: The effects of the aqueous seed extract of Syzygium cumini (ASc) in a
      short-term model of diabetes in rats are little explored. The present study was
      designed to evaluate the effect of the ASc on adenosine deaminase (ADA) activity
      and on biochemical and histopathological parameters in diabetic rats. METHODS:
      ASc (100 mg/kg) was administered for 21 days in control and streptozotocin (STZ)
      induced (60 mg/kg) diabetic rats. ADA activity, lipoperoxidation (cerebral
      cortex, kidney, liver and pancreas) and biochemical (serum) and histopathological
      (pancreas) parameters were evaluated. RESULTS: The main findings in this short
      term model of Diabetes mellitus (DM) were that the ASc (i) significantly reverted
      the increase of ADA activity in serum and kidney; (ii) ameliorated the
      lipoperoxidation in the cerebral cortex and pancreas of the diabetic group; (iii)
      demonstrated hypolipidemic and hypoglycemic properties and recovered the liver
      glycogen; and iv) prevented the HOMA-IR index increase in the diabetic group.
      Therefore, the ASc can be a positive factor for increasing the availability of
      substrates with significant protective actions, such as adenosine. Moreover, by
      maintaining glycogen and HOMA-IR levels, the extract could modulate the
      hyperglycemic state through the direct peripheral glucose uptake. CONCLUSIONS:
      Our data revealed that the short-term treatment with ASc has an important
      protective role under pathophysiological conditions caused by the early stage of
      DM. These results enhance our understanding of the effect of the ASc on the
      purinergic system in DM.

PMID- 25955282
TI  - The cytoskeleton as a drug target for neuroprotection: the case of the autism-
      mutated ADNP.
AB  - Fifteen years ago we discovered activity-dependent neuroprotective protein
      (ADNP), and showed that it is essential for brain formation/function. Our protein
      interaction studies identified ADNP as a member of the chromatin remodeling
      complex, SWI/SNF also associated with alternative splicing of tau and prediction
      of tauopathy. Recently, we have identified cytoplasmic ADNP interactions with the
      autophagy regulating microtubule-associated protein 1 light chain 3 (LC3) and
      with microtubule end-binding (EB) proteins. The ADNP-EB-binding SIP domain is
      shared with the ADNP snippet drug candidate, NAPVSIPQ termed NAP (davunetide).
      Thus, we identified a precise target for ADNP/NAP (davunetide) neuroprotection
      toward improved drug development. 

PMID- 25955285
TI  - Cord IGF-I concentrations in Indian newborns: associations with neonatal body
      composition and maternal determinants.
AB  - BACKGROUND: Indian newborns have been described as 'thin-fat' compared with
      European babies, but little is known about how this phenotype relates to the
      foetal growth factor IGF-I (insulin-like growth factor I) or its binding protein
      IGFBP-3. OBJECTIVE: To assess cord IGF-I and IGFBP-3 concentrations in a sample
      of Indian newborns and evaluate their associations with neonatal adiposity and
      maternal factors. METHODS: A prospective cohort study of 146 pregnant mothers
      with dietary, anthropometric and biochemical measurements at 28 and 34 weeks
      gestation. Neonatal weight, length, skin-folds, circumferences, and cord blood
      IGF-I and IGFBP-3 concentrations were measured at birth. RESULTS: Average cord
      IGF-I and IGFBP-3 concentrations were 46.6 (2.2) and 1269.4 (41) ng mL(-1) ,
      respectively. Girls had higher mean IGF-I than boys (51.4 ng mL(-1) vs. 42.9 ng
      mL(-1) ; P < 0.03), but IGFBP-3 did not differ. Cord IGF-I was positively
      correlated with all birth size measures except length, and most strongly with
      neonatal sum-of-skin-folds (r = 0.50, P < 0.001). IGFBP-3 was positively
      correlated with ponderal index, sum-of-skin-folds and placenta weight (r = 0.21,
      0.19, 0.16, respectively; P < 0.05). Of maternal demographic and anthropometric
      characteristics, only parity was correlated with cord IGF-I (r = 0.27, P <
      0.001). Among dietary behaviours, maternal daily milk intake at 34 weeks
      gestation predicted higher cord IGF-I compared to no-milk intake (51.8 ng mL(-1)
      vs. 36.5 ng mL(-1) , P < 0.01) after controlling for maternal characteristics,
      placental weight, and newborn gestational age, sex, weight and sum-of-skin-folds.
      Sum-of-skin-folds were positively associated with cord IGF-I in this multivariate
      model (57.3 ng mL(-1) vs. 35.1 ng mL(-1) for highest and lowest sum-of skin-fold
      quartile, P < 0.001). IGFBP-3 did not show significant relationships with these
      covariates. CONCLUSION: In this Indian study, cord IGF-I concentration was
      associated with greater adiposity among newborns. Maternal milk intake may play a
      role in this relationship.

PMID- 25955286
TI  - Peptide nucleic acid fluorescence in-situ hybridization for identification of
      Vibrio spp. in aquatic products and environments.
AB  - A peptide nucleic acid fluorescence in situ hybridization (PNA-FISH) method was
      developed for specific detection of the Vibrio genus. In silico analysis by BLAST
      and ProbeCheck showed that the designed PNA probe targeting the 16S rRNAs was
      suitable for specific identification of Vibrio. Specificity and sensitivity of
      the probe Vib-16S-1 were experimentally verified by its reactivity against 18
      strains of 9 Vibrio species and 14 non-Vibrio strains of 14 representative
      species. The PNA-FISH assay was able to identify 47 Vibrio positive samples from
      selectively enriched cultures of 510 samples of aquatic products and
      environments, comparable with the results obtained by biochemical identification
      and real-time PCR. We conclude that PNA-FISH can be an alternative method for
      rapid identification of Vibrio species in a broad spectrum of seafood or related
      samples. 

PMID- 25955287
TI  - Evaluation of the performance of Torulaspora delbrueckii, Williopsis saturnus,
      and Kluyveromyces lactis in lychee wine fermentation.
AB  - This study evaluated the effects of three non-Saccharomyces yeasts, namely
      Torulaspora delbrueckii PRELUDE, Williopsis saturnus NCYC22, and Kluyveromyces
      lactis KL71 on lychee juice fermentation. The fermentation performance of these
      non-Saccharomyces yeasts was significantly different. T. delbrueckii PRELUDE had
      the fastest rate of growth and high sugar consumption. W. saturnus NCYC22 used
      the lowest amount of sugars, but consumed the highest amount of nitrogen.
      Correspondingly, strain PRELUDE produced the highest level of ethanol (7.6% v/v),
      followed by strain KL71 (3.4% v/v) and strain NCYC22 (0.8% v/v). Aroma character
      impact terpenes and terpenoids could be partially retained in all lychee wines,
      with higher odour activity values (OAVs) of geraniol and citronellol in strain
      KL71. However, strain KL71 and strain NCYC22 over-produced ethyl acetate. Strain
      PRELUDE had a better ability to generate high levels of ethanol, isoamyl alcohol,
      2-phenylethyl alcohol, ethyl octanoate, and ethyl decanoate and retained high
      OAVs of lychee aroma-character compounds cis-rose oxide (16.5) and linalool
      (3.5). Thus, it is deemed to be a promising non-Saccharomyces yeast for lychee
      wine fermentation. 

PMID- 25955281
TI  - Current strategies and findings in clinically relevant post-translational
      modification-specific proteomics.
AB  - Mass spectrometry-based proteomics has considerably extended our knowledge about
      the occurrence and dynamics of protein post-translational modifications (PTMs).
      So far, quantitative proteomics has been mainly used to study PTM regulation in
      cell culture models, providing new insights into the role of aberrant PTM
      patterns in human disease. However, continuous technological and methodical
      developments have paved the way for an increasing number of PTM-specific
      proteomic studies using clinical samples, often limited in sample amount. Thus,
      quantitative proteomics holds a great potential to discover, validate and
      accurately quantify biomarkers in body fluids and primary tissues. A major effort
      will be to improve the complete integration of robust but sensitive proteomics
      technology to clinical environments. Here, we discuss PTMs that are relevant for
      clinical research, with a focus on phosphorylation, glycosylation and proteolytic
      cleavage; furthermore, we give an overview on the current developments and novel
      findings in mass spectrometry-based PTM research. 

PMID- 25955289
TI  - Enhancing vitamin B12 content in soy-yogurt by Lactobacillus reuteri.
AB  - More attention from the aged and vegetarians has been paid to soy-product due to
      its taste, easy digestibility, as well as the association with health. However,
      soy-product has a defect of low vitamin content, mainly the water-soluble vitamin
      B12. This study was to investigate co-fermentation of glycerol and fructose in
      soy-yogurt to enhance vitamin B12 production by Lactobacillus reuteri. After a
      serial combination experiments, the co-fermentation was confirmed to enhance the
      production of vitamin B12 up to 18 MUg/100mL. Both supplementations induced the
      expression of cobT and cbiA and functioned to balance the redox reaction.
      Meanwhile, high content of fructose supplementation reduced the production of
      vitamin B12 and suppressed expression of cobT in bacteria. It was proved that the
      vitamin B12 content of this soy-yogurt is higher than other fermented soybean
      based food and thus can be served as an alternative food for the aged and
      vegetarians.

PMID- 25955288
TI  - Relation between coumarate decarboxylase and vinylphenol reductase activity with
      regard to the production of volatile phenols by native Dekkera bruxellensis
      strains under 'wine-like' conditions.
AB  - Dekkera/Brettanomyces bruxellensis is considered a major cause of wine spoilage,
      and 4-ethylphenol and 4-ethylguaiacol are the most abundant off-aromas produced
      by this species. They are produced by decarboxylation of the corresponding
      hydroxycinnamic acids (HCAs), followed by a reduction of the intermediate 4
      vinylphenols. The aim of the present study was to examine coumarate decarboxylase
      (CD) and vinylphenol reductase (VR) enzyme activities in 5 native D. bruxellensis
      strains and determine their relation with the production of ethylphenols under
      'wine-like' conditions. In addition, biomass, cell culturability, carbon source
      utilization and organic acids were monitored during 60 days. All strains assayed
      turned out to have both enzyme activities. No significant differences were found
      in CD activity, whilst VR activity was variable among the strains. Growth of D.
      bruxellensis under 'wine-like' conditions showed two growth phases. Sugars were
      completely consumed during the first growth phase. Transformation of HCAs into
      ethylphenols also occurred during active growth of the yeast. No statistical
      differences were observed in volatile phenol levels produced by the strains
      growing under 'wine-like' conditions, independently of the enzyme activity
      previously recorded. Furthermore, our results demonstrate a relationship between
      the physiological state of D. bruxellensis and its ability to produce
      ethylphenols. Inhibition of growth of D. bruxellensis in wine seems to be the
      most efficient way to avoid ethylphenol production and the consequent loss of
      wine quality.

PMID- 25955290
TI  - Rapid pathogen detection by lateral-flow immunochromatographic assay with gold
      nanoparticle-assisted enzyme signal amplification.
AB  - To date most LF-ICA format for pathogen detection is based on generating color
      signals from gold nanoparticle (AuNP) tracers that are perceivable by naked eye
      but often these methods exhibit sensitivity lower than those associated with the
      conventional enzyme-based immunological methods or mandated by the regulatory
      guidelines. By developing AuNP avidin-biotin constructs in which a number of
      enzymes can be labeled we report on an enhanced LF-ICA system to detect pathogens
      at very low levels. With this approach we show that as low as 100 CFU/mL of
      Escherichia coli O157:H7 can be detected, indicating that the limit of detection
      can be increased by about 1000-fold due to our signal amplification approach. In
      addition, extensive cross-reactivity experiments were conducted (19 different
      organisms were used) to test and successfully validate the specificity of the
      assay. Semi-quantitative analysis can be performed using signal intensities which
      were correlated with the target pathogen concentrations for calibration by image
      processing.

PMID- 25955292
TI  - Interface Bonds Determined Gas-Sensing of SnO2-SnS2 Hybrids to Ammonia at Room
      Temperature.
AB  - Unique gas-sensing properties of semiconducting hybrids that are mainly related
      to the heterogeneous interfaces have been considerably reported. However, the
      effect of heterogeneous interfaces on the gas-sensing properties is still
      unclear, which hinders the development of semiconducting hybrids in gas-sensing
      applications. In this work, SnO2-SnS2 hybrids were synthesized by the oxidation
      of SnS2 at 300  degrees C with different times and exhibited high response to NH3
      at room temperature. With the increasing oxidation time, the relative
      concentration of interfacial Sn bonds, O-Sn-S, among the total Sn species of the
      SnO2-SnS2 hybrids increased first and then decreased. Interestingly, it can be
      found that the response of SnO2-SnS2 hybrids to NH3 at room temperature exhibited
      a strong dependence on the interfacial bonds. With more chemical bonds at the
      interface, the lower interface state density and the higher charge density of
      SnO2 led to more chemisorbed oxygen, resulting in a high response to NH3. Our
      results revealed the real roles of the heterogeneous interface in gas-sensing
      properties of hybrids and the importance of the interfacial bonds, which offers
      guidance for the material design to develop hybrid-based sensors. 

PMID- 25955293
TI  - Locus of control and coping strategies in older persons with and without
      depression.
AB  - OBJECTIVES: To compare locus of control and coping strategies in older persons
      with and without depression. METHOD: This cross-sectional study included 144
      depressed in-patients from seven psychogeriatric hospital units, and 106
      community-dwelling older persons without depression. All participants were 60
      years and older. Locus of control was assessed by a 17-items self-report
      questionnaire with six response categories. Coping strategies were assessed by a
      26-items self-report questionnaire with five response categories. For analytical
      purposes, age (<75 years vs. >=75 years), level of education (<10 years vs. >=10
      years) and general medical health (poor vs. not poor) were categorized. RESULTS:
      In linear regression analysis, controlling for demographics, health, and social
      variables, the depressed in-patients showed a higher external locus of control
      orientation and a less frequent use of problem-focused coping strategies compared
      with the non-depressed group. No differences in use of emotion-focused strategies
      were found between the two groups. CONCLUSION: Compared with the non-depressed
      old persons, the depressed hospitalized older persons were characterized by
      perceptions of less personal control, and less use of problem-focused strategies,
      what also might have brought positive alterations into their situation.

PMID- 25955291
TI  - Lipopolysaccharide pretreatment inhibits LPS-induced human umbilical cord
      mesenchymal stem cell apoptosis via upregulating the expression of cellular FLICE
      inhibitory protein.
AB  - Mesenchymal stem cell (MSC)-based regenerative therapy is currently regarded as a
      novel approach with which to repair damaged tissues. However, the efficiency of
      MSC transplantation is limited due to the low survival rate of engrafted MSCs.
      Lipopolysaccharide (LPS) production is increased in numerous diseases and serves
      an essential function in the regulation of apoptosis in a variety of cell types.
      Previous studies have indicated that low-dose LPS pretreatment contributes to
      cytoprotection. In the current study, LPS was demonstrated to induce apoptosis in
      human umbilical cord mesenchymal stem cells (hUCMSCs) via the activation of
      caspase, in a dose-dependent manner. Low-dose LPS pretreatment may protect
      hUCMSCs against apoptosis induced by high-dose LPS, by upregulating the
      expression of cellular FADD-like IL-1beta-converting enzyme-inhibitory protein (c
      FLIP). The results of the present study indicate that pretreatment with an
      appropriate concentration of LPS may alleviate high-dose LPS-induced apoptosis.

PMID- 25955294
TI  - Correction: Analysis of the Olive Fruit Fly Bactrocera oleae Transcriptome and
      Phylogenetic Classification of the Major Detoxification Gene Families.

PMID- 25955296
TI  - Correction: Thermodynamics of random reaction networks.

PMID- 25955295
TI  - Boswellia serrata Preserves Intestinal Epithelial Barrier from Oxidative and
      Inflammatory Damage.
AB  - Aminosalicylates, corticosteroids and immunosuppressants are currently the
      therapeutic choices in inflammatory bowel diseases (IBD), however, with limited
      remission and often serious side effects. Meanwhile complementary and alternative
      medicine (CAM) use is increasing, particularly herbal medicine. Boswellia serrata
      is a traditional Ayurvedic remedy with anti-inflammatory properties, of interest
      for its usefulness in IBDs. The mechanism of this pharmacological potential of
      Boswellia serrata was investigated in colonic epithelial cell monolayers exposed
      to H2O2 or INF-gamma+TNF-alpha, chosen as in vitro experimental model of
      intestinal inflammation. The barrier function was evaluated by the
      transepithelial electrical resistance (TEER) and paracellular permeability assay,
      and by the tight junction proteins (zonula occludens-1, ZO-1 and occludin)
      immunofluorescence. The expression of phosphorylated NF-kappaB and reactive
      oxygen species (ROS) generation were determined by immunoblot and
      cytofluorimetric assay, respectively. Boswellia serrata oleo-gum extract (BSE)
      and its pure derivative acetyl-11-keto-beta-boswellic acid (AKBA), were tested at
      0.1-10 MUg/ml and 0.027 MUg/ml, respectively. BSE and AKBA safety was
      demonstrated by no alteration of intestinal cell viability and barrier function
      and integrity biomarkers. H2O2 or INF-gamma+TNF-alpha treatment of Caco-2 cell
      monolayers significantly reduced TEER, increased paracellular permeability and
      caused the disassembly of tight junction proteins occludin and ZO-1. BSE and AKBA
      pretreatment significantly prevented functional and morphological alterations and
      also the NF-kappaB phosphorylation induced by the inflammatory stimuli. At the
      same concentrations BSE and AKBA counteracted the increase of ROS caused by H2O2
      exposure. Data showed the positive correlation of the antioxidant activity with
      the mechanism involved in the physiologic maintenance of the integrity and
      function of the intestinal epithelium. This study elucidates the pharmacological
      mechanisms mediated by BSE, in protecting intestinal epithelial barrier from
      inflammatory damage and supports its use as safe adjuvant in patients affected by
      IBD.

PMID- 25955297
TI  - Conversion of a Mono- and Diacylglycerol Lipase into a Triacylglycerol Lipase by
      Protein Engineering.
AB  - Despite the fact that most lipases are believed to be active against
      triacylglycerides, there is a small group of lipases that are active only on mono
      and diacylglycerides. The reason for this difference in substrate scope is not
      clear. We tried to identify the reasons for this in the lipase from Malassezia
      globosa. By protein engineering, and with only one mutation, we managed to
      convert this enzyme into a typical triacylglycerol lipase (the wild-type lipase
      does not accept triacylglycerides). The variant Q282L accepts a broad spectrum of
      triacylglycerides, although the catalytic behavior is altered to some extent.
      From in silico analysis it seems that specific hydrophobic interactions are key
      to the altered substrate specificity. 

PMID- 25955298
TI  - Let-7a regulates mammosphere formation capacity through Ras/NF-kappaB and
      Ras/MAPK/ERK pathway in breast cancer stem cells.
AB  - Breast cancer stem cells (BCSCs) have the greatest potential to maintain
      tumorigenesis in all subtypes of tumor cells and were regarded as the key drivers
      of tumor. Recent evidence has demonstrated that BCSCs contributed to a high
      degree of resistance to therapy. However, how BCSCs self renewal and
      tumorigenicity are maintained remains obscure. Herein, our study illustrated that
      overexpression of let-7a reduced cell proliferation and mammosphere formation
      ability of breast cancer stem cells(BCSCs) in a KRas-dependent manner through
      different pathways in vitro and in vivo. To be specific, we provided the evidence
      that let-7a was decreased, and reversely the expression of KRas was increased
      with moderate expression in early stages (I/II) and high expression in advanced
      stages (III/IV) in breast cancer specimens. In addition, the negative correlation
      between let-7a and KRas was clearly observed. In vitro, we found that let-7a
      inhibited mammosphere-forming efficiency and the mammosphere-size via NF-kappaB
      and MAPK/ERK pathway, respectively. The inhibitory effect of let-7a on
      mammosphere formation efficiency and the size of mammospheres was abolished after
      the depletion of KRas. On the contrary, enforced expression of KRas rescued the
      effect of let-7a. In vivo, let-7a inhibited the growth of tumors, whereas the
      negative effect of let-7a was rescued after overexpressing KRas. Taken together,
      our findings suggested that let-7a played a tumor suppressive role in a KRas
      dependent manner. 

PMID- 25955300
TI  - GnRH participates in the self-renewal of A549-derived lung cancer stem-like cells
      through upregulation of the JNK signaling pathway.
AB  - Lung cancer is the leading cause of cancer-related mortality in humans.
      Exploration of the mechanisms underlying the self-renewal and stemness
      maintenance of cancer stem-like cells (CSLCs) will open new avenues in lung
      cancer diagnosis and therapy. Here, we isolated and identified a subpopulation of
      lung cancer stem-like cells (LCSLCs) from non-small cell lung carcinoma (NSCLC)
      A549 cells with features including self-renewal capacity in vitro, elevated
      tumorigenic activity in vivo, and high expression of stemness markers CD44,
      CD133, aldehyde dehydrogenase 1 (ALDH1) and Sox2, using a serum-free suspension
      sphere-forming culture method. We then found a higher expression level of
      gonadotropin-releasing hormone (GnRH) in the LCSLCs using a microarray assay,
      suggesting that GnRH may play a role in the self-renewal capacity and stemness
      maintenance in lung cancer cells. In addition, the suppression of GnRH capacity
      negatively regulated self-renewal and stemness maintenance in the LCSLCs.
      Overexpression of GnRH promoted stemness properties of A549-derived LCSLCs,
      indicating that GnRH expression is essential for the self-renewal and stemness
      maintenance in LCSLCs. Moreover, further investigations demonstrated that the
      promotion of GnRH functions of self-renewal and stemness maintenance in LCSLCs
      was associated with the JNK signaling pathway. Therefore, our results showed that
      GnRH participates in the self-renewal capacity and stemness maintenance of LCSLCs
      by upregulating the JNK signaling pathway, and GnRH may be useful as an
      alternative LCSLC therapy.

PMID- 25955299
TI  - Tetraspanin Family Member, CD82, Regulates Expression of EZH2 via Inactivation of
      p38 MAPK Signaling in Leukemia Cells.
AB  - PURPOSE: We recently found that the tetraspanin family member, CD82, which is
      aberrantly expressed in chemotherapy-resistant CD34(+)/CD38- acute myelogenous
      leukemia (AML) cells, negatively regulates matrix metalloproteinase 9, and plays
      an important role in enabling CD34(+)/CD38(-) AML cells to adhere to the bone
      marrow microenvironment. This study explored novel functions of CD82 that
      contribute to AML progression. MATERIALS AND METHODS: We employed microarray
      analysis comparing the gene expression profiles between CD34(+)/CD38(-) AML cells
      transduced with CD82 shRNA and CD34(+)/CD38(-) AML cells transduced with control
      shRNA. Real-time RT-PCR and western blot analysis were performed to examine the
      effect of CD82 knockdown on the expression of the polycomb group member, enhancer
      of zeste homolog 2 (EZH2), in leukemia cells. A chromatin immunoprecipitation
      assay was performed to examine the effect of CD82 expression on the amount of
      EZH2 bound to the promoter regions of tumor suppressor genes in leukemia cells.
      We also utilized methylation-specific PCR to examine whether CD82 expression
      influences the methylation status of the tumor suppressor gene promoter regions
      in leukemia cells. RESULTS: Microarray analysis revealed that levels of EZH2
      decreased after shRNA-mediated depletion of CD82 in CD34(+)/CD38(-) AML cells.
      Moreover, the antibody-mediated blockade of CD82 in leukemia cells lowered EZH2
      expression via activation of p38 MAPK signaling, decreased the amount of EZH2
      bound to the promoter regions of the tumor suppressor genes, and inhibited
      histone H3 lysine 27 trimethylation in these promoter regions, resulting in
      upregulation of the tumor suppressors at both the mRNA and protein levels.

PMID- 25955301
TI  - Combined inhibition of MEK and mTOR has a synergic effect on angiosarcoma
      tumorgrafts.
AB  - Angiosarcoma (AS) is a rare neoplasm of endothelial origin that has limited
      treatment options and poor five-year survival. Using tumorgraft models, we
      previously showed that AS is sensitive to small-molecule inhibitors that target
      mitogen-activated/extracellular-signal-regulated protein kinase kinases 1 and 2
      (MEK). The objective of this study was to identify drugs that combine with MEK
      inhibitors to more effectively inhibit AS growth. We examined the in vitro
      synergy between the MEK inhibitor PD0325901 and inhibitors of eleven common
      cancer pathways in melanoma cell lines and canine angiosarcoma cell isolates.
      Combination indices were calculated using the Chou-Talalay method. Optimized
      combination therapies were evaluated in vivo for toxicity and efficacy using
      canine angiosarcoma tumorgrafts. Among the drugs we tested, rapamycin stood out
      because it showed strong synergy with PD0325901 at nanomolar concentrations. We
      observed that angiosarcomas are insensitive to mTOR inhibition. However,
      treatment with nanomolar levels of mTOR inhibitor renders these cells as
      sensitive to MEK inhibition as a melanoma cell line with mutant BRAF. Similar
      results were observed in B-Raf wild-type melanoma cells as well as in vivo, where
      treatment of canine AS tumorgrafts with MEK and mTOR inhibitors was more
      effective than monotherapy. Our data show that a low dose of an mTOR inhibitor
      can dramatically enhance angiosarcoma and melanoma response to MEK inhibition,
      potentially widening the field of applications for MEK-targeted therapy.

PMID- 25955302
TI  - Combined expression of ezrin and E-cadherin is associated with lymph node
      metastasis and poor prognosis in breast cancer.
AB  - Ezrin and E-cadherin have been known to play a role in tumor metastasis. However,
      the association between the expression of ezrin and E-cadherin in breast cancer
      patients remains unclear. In the present study, we investigated the expression of
      ezrin and E-cadherin in 275 breast cancer and 80 control patients with benign
      hyperplasia, using tissue microarray-based immunohistochemistry (IHC). Ezrin
      expression was higher, while that of E-cadherin was lower in breast cancer than
      in control samples. Ezrin expression was negatively correlated with E-cadherin
      expression in a subpopulation of breast cancer patients with a high expression of
      ezrin [ezrin(high)] and a low expression of E-cadherin [E-cad(low)]. The
      cytoplasmic expression of E-cadherin [E-cad(c)] occurred significantly more
      frequently in ezrin(high) breast cancer than in ezrin(low) breast cancer. The
      expression level of ezrin was significantly higher in breast cancer with E-cad(c)
      than that with a membrane expression of E-cadherin [E-cad(m)]. Ezrin(high) or E
      cad(low) expression was more associated with lymph node metastasis, and shorter
      overall survival (OS) and disease-free survival (DFS) in breast cancer patients.
      E-cad(c) was more associated with lymph node metastasis and shorter OS and DFS
      compared with E-cad(m). The combined expression of ezrin(high) and E-cad(low) or
      ezrin(high) and ezrin(c) was more associated with lymph node metastasis and poor
      prognosis. In addition, the multivariate Cox regression analysis revealed that
      lymph node metastasis and ezrin(high) expression were independent prognostic
      factors for shorter OS and DFS in breast cancer patients. The results of the
      present study suggested that ezrin promotes breast cancer metastasis via the
      regulation of E-cadherin expression.

PMID- 25955303
TI  - Documented atrial fibrillation recurrences after pulmonary vein isolation are
      associated with diminished quality of life.
AB  - AIMS: Pulmonary vein isolation (PVI) aims at eliminating symptomatic atrial
      fibrillation. In this regard, the most relevant indication for this procedure is
      the reduction of symptoms and improvement of quality of life (QoL) in patients
      who remain symptomatic despite antiarrhythmic drug treatment. We investigated the
      relation between documented atrial fibrillation recurrences and QoL in patients
      after PVI. METHODS: One hundred and six PVIs were performed in 99 patients.
      Follow-up was mainly performed at referring hospitals. Short Form 36 (SF-36) QoL
      questionnaires were completed before and 1 year after PVI. Electrocardiographic
      recordings from the first postprocedural year were retrospectively collected, 3
      months blanking excluded. Atrial fibrillation recurrence was defined as any
      recurrence of atrial arrhythmia documented on ECG or 24-h-Holter. RESULTS: Before
      PVI, patients had lower QoL than the general Dutch population in 7/8 SF-36
      questionnaire subscales (sumQoL 419.4 +/- 161 vs. 617.9, P < 0.001). Atrial
      fibrillation recurred in 52 (49%) patients. In these patients, four subscales
      increased following PVI (physical functioning P < 0.001, role physical P = 0.006,
      bodily pain P = 0.011 and social functioning P = 0.047). SumQoL remained lower
      than the general Dutch population (546.7 +/- 157, P = 0.003). In patients without
      documented recurrences, QoL improved to a level similar to that of the general
      Dutch population (602.9 +/- 148; P = 0.46). The number of electrocardiographic
      recordings was lower in the group without documented recurrences (2.5 +/- 1.8 vs.
      3.8 +/- 1.7, P = 0.002). CONCLUSION: In patients without documentation of atrial
      fibrillation, QoL increased up to the level of the general population after PVI,
      but it remained lower in patients with recurrences. In the latter group more ECGs
      were done, suggesting that QoL relates particularly to symptomatic episodes.
      Improvement of QoL is therefore an important attribute of PVI.

PMID- 25955304
TI  - Influence of accelerometer type and placement on physical activity energy
      expenditure prediction in manual wheelchair users.
AB  - PURPOSE: To assess the validity of two accelerometer devices, at two different
      anatomical locations, for the prediction of physical activity energy expenditure
      (PAEE) in manual wheelchair users (MWUs). METHODS: Seventeen MWUs (36 +/- 10 yrs,
      72 +/- 11 kg) completed ten activities; resting, folding clothes, propulsion on a
      1% gradient (3,4,5,6 and 7 km.hr-1) and propulsion at 4km.hr-1 (with an
      additional 8% body mass, 2% and 3% gradient) on a motorised wheelchair treadmill.
      GT3X+ and GENEActiv accelerometers were worn on the right wrist (W) and upper arm
      (UA). Linear regression analysis was conducted between outputs from each
      accelerometer and criterion PAEE, measured using indirect calorimetry. Subsequent
      error statistics were calculated for the derived regression equations for all
      four device/location combinations, using a leave-one-out cross-validation
      analysis. RESULTS: Accelerometer outputs at each anatomical location were
      significantly (p < .01) associated with PAEE (GT3X+-UA; r = 0.68 and GT3X+-W; r =
      0.82. GENEActiv-UA; r = 0.87 and GENEActiv-W; r = 0.88). Mean +/- SD PAEE
      estimation errors for all activities combined were 15 +/- 45%, 14 +/- 50%, 3 +/-
      25% and 4 +/- 26% for GT3X+-UA, GT3X+-W, GENEActiv-UA and GENEActiv-W,
      respectively. Absolute PAEE estimation errors for devices varied, 19 to 66% for
      GT3X+-UA, 17 to 122% for GT3X+-W, 15 to 26% for GENEActiv-UA and from 17.0 to 32%
      for the GENEActiv-W. CONCLUSION: The results indicate that the GENEActiv device
      worn on either the upper arm or wrist provides the most valid prediction of PAEE
      in MWUs. Variation in error statistics between the two devices is a result of
      inherent differences in internal components, on-board filtering processes and
      outputs of each device.

PMID- 25955305
TI  - MicroRNA-137 suppresses tumor growth in epithelial ovarian cancer in vitro and in
      vivo.
AB  - Epithelial ovarian cancer (EOC) remains a major gynecological problem, with a
      poor 5-year-survival rate due to distant metastases. The identification of
      microRNAs (miRNAs) may provide a novel avenue for diagnostic and treatment
      regimens for EOC. Several miRNAs have been reported to be involved in the
      progression of EOC, among which miRNA (miR)-137 has been observed to be
      downregulated in the ovarian tissues of patients with EOC. However, the functions
      of miR-137 in EOC cell apoptosis, migration and invasion remain to be elucidated.
      In the present study, the expression of miR-137 was measured in clinical ovarian
      cancer specimens and cell lines using reverse transcription-quantitative
      polymerase chain reaction. The role of miR-137 in the growth and survival of the
      SKOV3 human ovarian cancer cell line was determined using several in vitro
      approaches and in nude mouse models. The results demonstrated that the expression
      of miR-137 was downregulated in the ovarian cancer specimens and cell lines. It
      was also observed that enforced expression of miR-137 in the EOC cell lines
      decreased cell proliferation, clonogenicity, migration and invasion, and induced
      G1 arrest and cell apoptosis in vitro. Notably, the enforced expression of miR
      137 suppressed tumor growth in the nude mice models. These findings suggested
      that miR-137 may act as a tumor suppressor and be used as a potential therapeutic
      agent for the treatment of EOC.

PMID- 25955306
TI  - Near-complete structural characterization of phosphatidylcholines using electron
      impact excitation of ions from organics.
AB  - Although lipids are critical components of many cellular assemblies and
      biological pathways, accurate descriptions of their molecular structures remain
      difficult to obtain. Many benchtop characterization methods require arduous and
      time-consuming procedures, and multiple assays are required whenever a new
      structural feature is probed. Here, we describe a new mass-spectrometry-based
      workflow for enhanced structural lipidomics that, in a single experiment, can
      yield almost complete structural information for a given glycerophospholipid
      (GPL) species. This includes the lipid's sum (Brutto) composition from the
      accurate mass measured for the intact lipid ion and the characteristic headgroup
      fragment, the regioisomer composition from fragment ions unique to the sn-1 and
      sn-2 positions, and the positions of carbon-carbon double bonds in the lipid acyl
      chains. Here, lipid ions are fragmented using electron impact excitation of ions
      from organics (EIEIO)--a technique where the singly charged lipid ions are
      irradiated by an electron beam, producing diagnostic product ions. We have
      evaluated this methodology on various lipid standards, as well as on a biological
      extract, to demonstrate this new method's utility.

PMID- 25955307
TI  - Molecular Characterization and Expression Profiles of Polygalacturonase Genes in
      Apolygus lucorum (Hemiptera: Miridae).
AB  - Polygalacturonase (PG) is an enzyme in the salivary glands of piercing-sucking
      mirid bugs (Hemiptera: Miridae) that plays a key role in plant feeding and
      injury. By constructing a full-length cDNA library, we cloned and characterized
      14 PG genes from the salivary glands of Apolygus lucorum, a pestiferous mirid bug
      in cotton, fruit trees and other crops in China. BLAST search analysis showed
      that the amino acid sequences deduced from transcripts of the PG genes were
      closely related to PGs from other mirid bugs. Phylogenetic analysis showed that
      the PGs of mirid bugs had six main branches, PG1-PG6 (Genbank accession numbers:
      KF881899~KF881912). We investigated the mRNA expression patterns of the A.
      lucorum PG genes using real-time PCR. All 14 PGs were expressed significantly
      higher in the salivary glands than in other tissues (head, thorax, abdomen, leg
      and wing). For eggs and nymphs, the expression levels of these PGs were much
      higher in the 5th instar stage than in the egg, and 1st and 3rd instar stages.
      The PG expression levels in 1-day-old adults were very low, and increased in 5,
      20 and 30-day-old adults. Additionally, PG expression levels were generally
      similar between males and females. The possible physiological functions of PGs in
      A. lucorum were discussed. 

PMID- 25955308
TI  - Effect on Electron Structure and Magneto-Optic Property of Heavy W-Doped Anatase
      TiO2.
AB  - The spin or nonspin state of electrons in W-doped anatase TiO2 is very difficult
      to judge experimentally because of characterization method limitations. Hence,
      the effect on the microscopic mechanism underlying the visible-light effect of W
      doped anatase TiO2 through the consideration of electronic spin or no-spin states
      is still unknown. To solve this problem, we establish supercell models of W-doped
      anatase TiO2 at different concentrations, followed by geometry optimization and
      energy calculation based on the first-principle planewave norm conserving pseudo
      potential method of the density functional theory. Calculation results showed
      that under the condition of nonspin the doping concentration of W becomes
      heavier, the formation energy becomes greater, and doping becomes more difficult.
      Meanwhile, the total energy increases, the covalent weakens and ionic bonds
      strengthens, the stability of the W-doped anatase TiO2 decreases, the band gap
      increases, and the blue-shift becomes more significant with the increase of W
      doping concentration. However, under the condition of spin, after the band gap
      correction by the GGA+U method, it is found that the semimetal diluted magnetic
      semiconductors can be formed by heavy W-doped anatase TiO2. Especially, a
      conduction electron polarizability of as high as near 100% has been found for the
      first time in high concentration W-doped anatase TiO2. It will be able to be a
      promising new type of dilute magnetic semiconductor. And the heavy W-doped
      anatase TiO2 make the band gap becomes narrower and absorption spectrum red
      shift. 

PMID- 25955309
TI  - Intracranial Infectious Aneurysm in Orbital Cellulitis.
AB  - Infectious intracranial aneurysm and cavernous sinus thrombosis are rare
      complications of orbital cellulitis. We report the case of a 46-year-old male
      presenting with sinusitis and orbital cellulitis complicated by the development
      of an orbital mass. Following orbitotomy with debulking, the patient underwent
      bony orbital decompression for increasing proptosis postoperatively. While his
      exam stabilized, the patient developed complete ptosis and extraocular motor
      palsy in the contralateral eye after undergoing bilateral sinus debridement.
      Imaging was notable for the presence of a pseudoaneurysm of the internal carotid
      artery, which was treated with a stent. This report demonstrates rare
      complications of orbital cellulitis. These patients should be monitored carefully
      with noninvasive imaging studies, such as cerebral angiography, for early
      detection of vascular abnormalities that can progress rapidly. 

PMID- 25955310
TI  - Balancing the Needs of China's Wetland Conservation and Rice Production.
AB  - China's rice policy for protecting paddy fields and constructing rice production
      bases is in conflict with its wetland conservation strategy. The policy will
      increase the rice planting area, the loss of remaining wetlands, and
      environmental pollution, with intensive application of fertilizers and heavy use
      of pesticides. The key to resolving this conflict is to bring rice production in
      compliance with wetland conservation and sustainable agriculture. An operational,
      sound regulatory program is needed to improve China's wetland conservation. Using
      wetland conservation in the US as an example, we argue that more effective
      technical guidelines for wetland inventory and monitoring are necessary to
      support the implementation of the regulatory program. Agricultural conservation
      programs are also needed to stop further wetland loss from agricultural usages.
      An ecoagricultural strategy and practice should be adopted for rice production to
      reduce pollution and loss of remaining wetlands. Agroecological engineering tools
      can be used to reduce the impacts of nutrient- and pesticide-enriched
      agricultural runoff to wetlands. 

PMID- 25955311
TI  - Maximal expression of Foxl2 in pituitary gonadotropes requires ovarian hormones.
AB  - Gonadotropin-releasing hormone (GnRH) and activin regulate synthesis of FSH and
      ultimately fertility. Recent in vivo studies cast SMAD4 and FOXL2 as master
      transcriptional mediators of activin signaling that act together and
      independently of GnRH to regulate Fshb gene expression and female fertility.
      Ovarian hormones regulate GnRH and its receptor (GNRHR) through negative and
      positive feedback loops. In contrast, the role of ovarian hormones in regulating
      activin, activin receptors, and components of the activin signaling pathway,
      including SMAD4 and FOXL2, remains understudied. The widespread distribution of
      activin and many of its signaling intermediates complicates analysis of the
      effects of ovarian hormones on their synthesis in gonadotropes, one of five
      pituitary cell types. We circumvented this complication by using a transgenic
      model that allows isolation of polyribosomes selectively from gonadotropes of
      intact females and ovariectomized females treated with or without a GnRH
      antagonist. This paradigm allows assessment of ovarian hormonal feedback and
      distinguishes responses that are either independent or dependent on GnRH.
      Surprisingly, our results indicate that Foxl2 levels in gonadotropes decline
      significantly in the absence of ovarian input and independently of GnRH.
      Expression of the genes encoding other members of the activin signaling pathway
      are unaffected by loss of ovarian hormonal feedback, highlighting their selective
      effect on Foxl2. Expression of Gnrhr, a known target of FOXL2, also declines upon
      ovariectomy consistent with reduced expression of Foxl2 and loss of ovarian
      hormones. In contrast, Fshb mRNA increases dramatically post-ovariectomy due to
      increased compensatory input from GnRH. Together these data suggest that ovarian
      hormones regulate expression of Foxl2 thereby expanding the number of genes
      controlled by the hypothalamic-pituitary-gonadal axis that ultimately dictate
      reproductive fitness. 

PMID- 25955313
TI  - QTc modification after risperidone administration--insight into the mechanism of
      action with use of the modeling and simulation at the population level approach.
AB  - CONTEXT: Ensuring the safety of therapy is both expensive and time-consuming
      process, which may be supported by modeling and simulation. OBJECTIVE: The
      objective of this study was to gain insight into the effect of risperidone
      administration on QT interval by in silico evaluation of the effect in the
      individuals with different metabolic status of CYP2D6. MATERIALS AND METHODS:
      Evaluation was performed through the combination of empirical and mechanistic
      modeling with the use of the Cardiac Safety Simulator platform allowing for
      simulation of electrophysiological consequences of drug administration at the
      population level. The performance of the proposed approach was evaluated by in
      silico mimicking of the clinical trial conducted by Novalbos. RESULTS: The
      simulation results depict differences in DeltaQT correlated with change in
      metabolic activity, but not as significant as observed clinically. For poor
      metabolizers (PMs), DeltaQTc was 8.0 and 5.1 ms, for Fridericia's and Bezett's
      correction, respectively, in comparison to 13.9 in Novalbos's study. For
      intermediate metabolizers (IMs), there was 9.3 and 7.3 ms versus 4 ms observed
      clinically, for ultrarapid metabolizers (UMs) -4.0 and 1 ms versus 0.60 ms, for
      EMs -5.9 and 7.7 ms versus 6.1 ms. DISCUSSION AND CONCLUSION: Simulated results
      underestimate changes observed in the PMs and overestimate the results for the
      IMs and UMs groups. EM individuals were properly predicted. The results of
      various QTc studies vary considerably and it is not clear which factors have a
      decisive influence. Nevertheless, presented differences are still more consistent
      with clinical results than results obtained clinically by other researchers.

PMID- 25955314
TI  - Considerable exposure to the endocrine disrupting chemicals phthalates and
      bisphenol-A in intensive care unit (ICU) patients.
AB  - Critical care medicine has largely benefited from plastic-containing medical
      devices. However, bisphenol-A (BPA) and phthalates present in the plastics can
      leach from such devices. We hypothesized that intensive care unit (ICU) patients
      are exposed to BPA and phthalates through (plastic) medical devices. Serum (n =
      118) and urine (n= 102) samples of adult ICU patients (n = 35) were analyzed for
      total BPA and phthalate metabolites (PMs). Our results showed that adult ICU
      patients are continuously exposed to phthalates, such as di(2
      ethylhexyl)phthalate (DEHP), as well as to BPA, albeit to a lesser extent. This
      exposure resulted in detectable high serum and urinary levels in almost every
      patient and at every studied time point. Moreover, these levels were
      significantly higher than in controls or compared to referenced literature. The
      chronology of exposure was demonstrated: pre-operative urinary and serum levels
      of the DEHP metabolites were often below the detection limit. Plastic-containing
      medical devices were the main source of DEHP exposure: post-operative patients on
      hemofiltration, extracorporeal membrane oxygenation or both showed serum levels
      100-or 1000-fold higher than the levels in the general population reported in the
      literature. The serum and some of the urinary levels of the DEHP metabolites are
      the highest ever reported in humans; some at biologically highly relevant
      concentrations of >= 10-50 MUM. Despite the continuously tightening regulations,
      BPA and DEHP appear to be still present in (some) medical devices. Because
      patient safety is a concern in the ICU, further research into the (possibly toxic
      and clinical) effects of these chemicals released from medical devices is
      imperiously necessary.

PMID- 25955312
TI  - Cell Specific eQTL Analysis without Sorting Cells.
AB  - The functional consequences of trait associated SNPs are often investigated using
      expression quantitative trait locus (eQTL) mapping. While trait-associated
      variants may operate in a cell-type specific manner, eQTL datasets for such cell
      types may not always be available. We performed a genome-environment interaction
      (GxE) meta-analysis on data from 5,683 samples to infer the cell type specificity
      of whole blood cis-eQTLs. We demonstrate that this method is able to predict
      neutrophil and lymphocyte specific cis-eQTLs and replicate these predictions in
      independent cell-type specific datasets. Finally, we show that SNPs associated
      with Crohn's disease preferentially affect gene expression within neutrophils,
      including the archetypal NOD2 locus. 

PMID- 25955315
TI  - The Impact of Climate Trends on a Tick Affecting Public Health: A Retrospective
      Modeling Approach for Hyalomma marginatum (Ixodidae).
AB  - The impact of climate trends during the period 1901-2009 on the life cycle of
      Hyalomma marginatum in Europe was modeled to assess changes in the physiological
      processes of this threat to public health. Monthly records of temperature and
      water vapour at a resolution of 0.5 degrees  and equations describing the life
      cycle processes of the tick were used. The climate in the target region affected
      the rates of the life cycle processes of H. marginatum: development rates
      increased, mortality rates in molting stages decreased, and the survival rates of
      questing ticks decreased in wide territories of the Mediterranean basin. The
      modeling framework indicated the existence of critical areas in the Balkans,
      central Europe, and the western coast of France, where the physiological
      processes of the tick improved to extents that are consistent with the
      persistence of populations if introduced. A spatially explicit risk assessment
      was performed to detect candidate areas where active surveys should be performed
      to monitor changes in tick density or persistence after a hypothetical
      introduction. We detected areas where the critical abiotic (climate) and biotic
      (host density) factors overlap, including most of the Iberian peninsula, the
      Mediterranean coast of France, eastern Turkey, and portions of the western Black
      Sea region. Wild ungulate densities are unavailable for large regions of the
      territory, a factor that might affect the outcome of the study. The risk of
      successfully establishing H. marginatum populations at northern latitudes of its
      current colonization range seems to be still low, even if the climate has
      improved the performance of the tick in these areas. 

PMID- 25955316
TI  - The CXCR4/CXCR7/CXCL12 Axis Is Involved in a Secondary but Complex Control of
      Neuroblastoma Metastatic Cell Homing.
AB  - Neuroblastoma (NB) is one of the most deadly solid tumors of the young child, for
      which new efficient and targeted therapies are strongly needed. The
      CXCR4/CXCR7/CXCL12 chemokine axis has been involved in the progression and organ
      specific dissemination of various cancers. In NB, CXCR4 expression was shown to
      be associated to highly aggressive undifferentiated tumors, while CXCR7
      expression was detected in more differentiated and mature neuroblastic tumors. As
      investigated in vivo, using an orthotopic model of tumor cell implantation of
      chemokine receptor-overexpressing NB cells (IGR-NB8), the CXCR4/CXCR7/CXCL12 axis
      was shown to regulate NB primary and secondary growth, although without any
      apparent influence on organ selective metastasis. In the present study, we
      addressed the selective role of CXCR4 and CXCR7 receptors in the homing phase of
      metastatic dissemination using an intravenous model of tumor cell implantation.
      Tail vein injection into NOD-scid-gamma mice of transduced IGR-NB8 cells
      overexpressing CXCR4, CXCR7, or both receptors revealed that all transduced cell
      variants preferentially invaded the adrenal gland and typical NB metastatic
      target organs, such as the liver and the bone marrow. However, CXCR4 expression
      favored NB cell dissemination to the liver and the lungs, while CXCR7 was able to
      strongly promote NB cell homing to the adrenal gland and the liver. Finally,
      coexpression of CXCR4 and CXCR7 receptors significantly and selectively increased
      NB dissemination toward the bone marrow. In conclusion, CXCR4 and CXCR7 receptors
      may be involved in a complex and organ-dependent control of NB growth and
      selective homing, making these receptors and their inhibitors potential new
      therapeutic targets. 

PMID- 25955317
TI  - Role of the bradykinin B2 receptor in a rat model of local heart irradiation.
AB  - PURPOSE: Radiation-induced heart disease (RIHD) is a delayed effect of
      radiotherapy for cancers of the chest, such as breast, esophageal, and lung.
      Kinins are small peptides with cardioprotective properties. We previously used a
      rat model that lacks the precursor kininogen to demonstrate that kinins are
      involved in RIHD. Here, we examined the role of the kinin B2 receptor (B2R) in
      early radiation-induced signaling in the heart. MATERIALS AND METHODS: Male Brown
      Norway rats received the B2R-selective antagonist HOE-140 (icatibant) via osmotic
      minipump from 5 days before until 4 weeks after 21 Gy local heart irradiation. At
      4 weeks, signaling events were measured in left ventricular homogenates and
      nuclear extracts using western blotting and real-time polymerase chain reaction.
      Numbers of CD68-positive (monocytes/macrophages), CD2-positive (T-lymphocytes),
      and mast cells were measured using immunohistochemistry. RESULTS: Radiation
      induced c-Jun phosphorylation and nuclear translocation were enhanced by HOE-140.
      HOE-140 did not modify endothelial nitric oxide synthase (eNOS) phosphorylation
      or alter numbers of CD2-positive or mast cells, but enhanced CD68-positive cell
      counts in irradiated hearts. CONCLUSIONS: B2R signaling may regulate
      monocyte/macrophage infiltration and c-Jun signals in the irradiated heart.
      Although eNOS is a main target for kinins, the B2R may not regulate eNOS
      phosphorylation in response to radiation.

PMID- 25955318
TI  - Involvement of enhancer of zeste homolog 2 in cisplatin-resistance in ovarian
      cancer cells by interacting with several genes.
AB  - In the present study, gene expression profiles of cisplatin-sensitive ovarian
      cancer (OC) cells were compared with those of cisplatin-resistant OC cells to
      identify key genes and pathways contributing to cisplatin resistance in ovarian
      cancer cells. The GSE15372 gene expression data set was downloaded from Gene
      Expression Omnibus, and included five biological replicates of cisplatin
      sensitive OC cells and five biological replicates of cisplatin-resistant OC
      cells. Differentially expressed genes (DEGs) were screened using the limma
      package in R, based on the cut-off values of P<0.05 and |log2 (fold change)|>1.
      Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and Gene
      Ontology enrichment analysis were performed on the DEGs using the Database for
      Annotation, Visualization and Integration Discovery. The protein-protein
      interaction (PPI) network was constructed for the DEGs using STRING, and sub
      networks were analyzed by Clustering with Overlapping Neighborhood Expansion. A
      total of 556 DEGs were identified in the cisplatin-sensitive OC cells, of which
      246 were upregulated and 310 were downregulated. Functional enrichment analysis
      revealed metabolism-associated pathways, DNA replication and cell cycle were
      significantly enriched in the downregulated genes, while cell growth and
      differentiation, response to stimulus, and apoptosis were significantly enriched
      in the upregulated genes. A PPI network, including 342 nodes was constructed for
      the DEGs and four subnetworks were extracted from the entire network. A total of
      34 DEGs interacting with enhancer of zeste homolog 2 (EZH2) were identified,
      which were associated with DNA replication, pyrimidine metabolism and cell cycle.
      In conclusion, a number of key genes and pathways associated with the cisplatin
      resistance of OC were revealed, particularly EZH2. These findings assist in the
      development of therapy for OC.

PMID- 25955320
TI  - Xenogeneic Mesenchymal Stromal Cells Improve Wound Healing and Modulate the
      Immune Response in an Extensive Burn Model.
AB  - Major skin burns are difficult to treat. Patients often require special care and
      long-term hospitalization. Besides specific complications associated with the
      wounds themselves, there may be impairment of the immune system and of other
      organs. Mesenchymal stromal cells (MSCs) are a recent therapeutic alternative to
      treat burns, mainly aiming to accelerate the healing process. Several MSC
      properties favor their use as therapeutic approach, as they promote angiogenesis,
      stimulate regeneration, and enhance the immunoregulatory function. Moreover,
      since patients with extensive burns require urgent treatment and because the
      expansion of autologous MSCs is a time-consuming process, in this present study
      we chose to evaluate the therapeutic potential of xenogeneic MSCs in the
      treatment of severe burns in rats. MSCs were isolated from mouse bone marrow,
      expanded in vitro, and intradermally injected in the periphery of burn wounds.
      MSC-treated rats presented higher survival rates (76.19%) than control animals
      treated with PBS (60.86%, p < 0.05). In addition, 60 days after the thermal
      injury, the MSC-treated group showed larger proportion of healed areas within the
      burn wounds (90.81 +/- 5.05%) than the PBS-treated group (76.11 +/- 3.46%, p =
      0.03). We also observed that CD4(+) and CD8(+) T cells in spleens and in damaged
      skin, as well as the percentage of neutrophils in the burned area, were modulated
      by MSC treatment. Plasma cytokine (TGF-beta, IL-10, IL-6, and CINC-1) levels were
      also altered in the MSC-treated rats, when compared to controls. Number of
      injected GFP(+) MSCs progressively decreased over time, and 60 days after
      injection, few MSCs were still detected in the skin of treated animals. This
      study demonstrates the therapeutic effectiveness of intradermal application of
      MSCs in a rat model of deep burns, providing basis for future regenerative
      therapies in patients suffering from deep burn injuries. 

PMID- 25955319
TI  - Finasteride concentrations and prostate cancer risk: results from the Prostate
      Cancer Prevention Trial.
AB  - OBJECTIVE: In the Prostate Cancer Prevention Trial (PCPT), finasteride reduced
      the risk of prostate cancer by 25%, even though high-grade prostate cancer was
      more common in the finasteride group. However, it remains to be determined
      whether finasteride concentrations may affect prostate cancer risk. In this
      study, we examined the association between serum finasteride concentrations and
      the risk of prostate cancer in the treatment arm of the PCPT and determined
      factors involved in modifying drug concentrations. METHODS: Data for this nested
      case-control study are from the PCPT. Cases were drawn from men with biopsy
      proven prostate cancer and matched controls. Finasteride concentrations were
      measured using a liquid chromatography-mass spectrometry validated assay. The
      association of serum finasteride concentrations with prostate cancer risk was
      determined by logistic regression. We also examine whether polymorphisms in the
      enzyme target and metabolism genes of finasteride are related to drug
      concentrations using linear regression. RESULTS AND CONCLUSIONS: Among men with
      detectable finasteride concentrations, there was no association between
      finasteride concentrations and prostate cancer risk, low-grade or high-grade,
      when finasteride concentration was analyzed as a continuous variable or
      categorized by cutoff points. Since there was no concentration-dependent effect
      on prostate cancer, any exposure to finasteride intake may reduce prostate cancer
      risk. Of the twenty-seven SNPs assessed in the enzyme target and metabolism
      pathway, five SNPs in two genes, CYP3A4 (rs2242480; rs4646437; rs4986910), and
      CYP3A5 (rs15524; rs776746) were significantly associated with modifying
      finasteride concentrations. These results suggest that finasteride exposure may
      reduce prostate cancer risk and finasteride concentrations are affected by
      genetic variations in genes responsible for altering its metabolism pathway.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT00288106.

PMID- 25955323
TI  - Total pancreatectomy and islet autotransplantation for chronic pancreatitis:
      breaking down barriers.

PMID- 25955321
TI  - Differences in Lower Extremity and Trunk Kinematics between Single Leg Squat and
      Step Down Tasks.
AB  - The single leg squat and single leg step down are two commonly used functional
      tasks to assess movement patterns. It is unknown how kinematics compare between
      these tasks. The purpose of this study was to identify kinematic differences in
      the lower extremity, pelvis and trunk between the single leg squat and the step
      down. Fourteen healthy individuals participated in this research and performed
      the functional tasks while kinematic data were collected for the trunk, pelvis,
      and lower extremities using a motion capture system. For the single leg squat
      task, the participant was instructed to squat as low as possible. For the step
      down task, the participant was instructed to stand on top of a box, slowly lower
      him/herself until the non-stance heel touched the ground, and return to standing.
      This was done from two different heights (16 cm and 24 cm). The kinematics were
      evaluated at peak knee flexion as well as at 60 degrees  of knee flexion. Pearson
      correlation coefficients (r) between the angles at those two time points were
      also calculated to better understand the relationship between each task. The
      tasks resulted in kinematics differences at the knee, hip, pelvis, and trunk at
      both time points. The single leg squat was performed with less hip adduction (p
      <= 0.003), but more hip external rotation and knee abduction (p <= 0.030), than
      the step down tasks at 60 degrees  of knee flexion. These differences were
      maintained at peak knee flexion except hip external rotation was only significant
      in the 24 cm step down task (p <= 0.029). While there were multiple differences
      between the two step heights at peak knee flexion, the only difference at 60
      degrees  of knee flexion was in trunk flexion (p < 0.001). Angles at the knee and
      hip had a moderate to excellent correlation (r = 0.51-0.98), but less
      consistently so at the pelvis and trunk (r = 0.21-0.96). The differences in
      movement patterns between the single leg squat and the step down should be
      considered when selecting a single leg task for evaluation or treatment. The high
      correlation of knee and hip angles between the three tasks indicates that similar
      information about knee and hip kinematics was gained from each of these tasks,
      while pelvis and trunk angles were less well predicted.

PMID- 25955324
TI  - Reference range of serum calcitonin in pediatric population.
AB  - BACKGROUND: Children belonging to the multiple endocrine neoplasia type 2 (MEN 2)
      pedigree and carrying germline RET mutations are candidates for prophylactic
      thyroidectomy, the timing of which is based on the mutation-associated risk and
      the calcitonin (CT) levels. DESIGN: The aim of this study was to establish the
      reference range for serum CT in a pediatric population. The study included 2740
      subjects (1339 females and 1401 males) ranging in age from 1 day to 16 years and
      undergoing blood testing for any medical condition not affecting serum CT.
      RESULTS: Overall, serum CT was undetectable in 61.5% of the samples and
      detectable in 38.5%. Detectable samples were more frequent in the first 2 years
      of life. Thereafter, undetectable samples became more frequent, particularly in
      females. Mean serum CT concentrations were higher in the first year of life (9.81
      +/- 8.8 pg/mL; range, 2.0-48.9 pg/mL) and the second year of life (4.56 +/- 2.64
      pg/mL; range, 2.0-14.7 pg/mL). A significant decrease of serum CT levels was
      observed thereafter (P < .001), and starting from the third year of life serum CT
      levels were similar to those found in adults. No gender difference was found in
      any age group. Based on these results, age-specific CT reference ranges are
      needed in the pediatric population, and especially in the first 2 years of life.
      CONCLUSIONS: This is the first study defining the reference range for serum CT in
      the pediatric population and large enough to be statistically meaningful. Our
      proposal may facilitate the process of decision making when dealing with gene
      carriers of MEN 2.

PMID- 25955325
TI  - Corrigendum.

PMID- 25955322
TI  - Impact of Smoking and Brain Metastasis on Outcomes of Advanced EGFR Mutation Lung
      Adenocarcinoma Patients Treated with First Line Epidermal Growth Factor Receptor
      Tyrosine Kinase Inhibitors.
AB  - OBJECTIVES: This purpose of this study was to examine clinical-pathologic factors
      -particularly smoking and brain metastases--in EGFR mutation positive (M(+)) lung
      adenocarcinoma (ADC) to determine their impact on survival in patients treated
      with first line EGFR TKI. METHODS: A retrospective review of EGFR mutation reflex
      testing experience for all ADC diagnosed at a tertiary Asian cancer centre from
      January 2009 to April 2013. Amongst this cohort, patients with advanced EGFR M(+)
      ADC treated with first line EGFR TKI were identified to determine factors that
      influence progression free and overall survival. RESULTS: 444/742 (59.8%) ADC
      reflex tested for EGFR mutations were EGFR M(+.) Amongst never-smokers (n=468),
      EGFR M(+) were found in 74.5% of females and 76.3% of males, and amongst ever
      smokers (n=283), in 53.3% of females and 35.6% of males. Exon 20 mutations were
      found more commonly amongst heavy smokers (> 50 pack years and > 20 pack years,
      Pearson's chi square p=0.044, and p=0.038 respectively). 211 patients treated
      with palliative first line TKI had a median PFS and OS of 9.2 and 19.6 months
      respectively. 26% of patients had brain metastasis at diagnosis. This was
      significantly detrimental to overall survival (HR 1.85, CI 1.09-3.16, p=0.024) on
      multivariate analysis. There was no evidence that smoking status had a
      significant impact on survival. CONCLUSIONS: The high prevalence of EGFR M(+) in
      our patient population warrants reflex testing regardless of gender and smoking
      status. Smoking status and dosage did not impact progression free or overall
      survival in patients treated with first line EGFR TKI. The presence of brain
      metastasis at diagnosis negatively impacts overall survival.

PMID- 25955326
TI  - Erratum.

PMID- 25955327
TI  - Withdrawal.

PMID- 25955330
TI  - Letter to the editor: Comment on Pagets disease clinical practice guideline by
      Singer et al.

PMID- 25955331
TI  - Response to letter.

PMID- 25955333
TI  - Cu-catalyzed silylation of alkynes: a traceless 2-pyridylsulfonyl controller
      allows access to either regioisomer on demand.
AB  - The Cu-catalyzed silylation of terminal and internal alkynes bearing a 2-pyridyl
      sulfonyl group (SO2Py) at the propargylic position affords a breadth of vinyl
      silanes in good yields and with excellent regio- and stereocontrol under mild
      conditions. The directing SO2Py group is essential in terms of reaction
      efficiency and chemoselectivity. Importantly, this group also provides the
      ability to reverse the regiochemical outcome of the reaction, opening the access
      to either regioisomer without modification of the starting substrate by virtue of
      an in situ base-promoted alkyne to allene equilibration which takes place prior
      to the silylcupration process. Furthermore, removal of the directing SO2Py allows
      for further elaboration of the silylation products. In particular, a one-pot
      tandem alkyne silylation/allylic substitution sequence, in which both steps are
      catalyzed by the same Cu species, opens up a new approach for the access to
      either formal hydrosilylation regioisomer of unsymmetrical aliphatic-substituted
      internal alkynes from propargyl sulfones. 

PMID- 25955332
TI  - Trends in Tracheostomy for Mechanically Ventilated Patients in the United States,
      1993-2012.
AB  - RATIONALE: National trends in tracheostomy for mechanical ventilation (MV)
      patients are not well characterized. OBJECTIVES: To investigate trends in
      tracheostomy use, timing, and outcomes in the United States. METHODS: We
      calculated estimates of tracheostomy use and outcomes from the National Inpatient
      Sample from 1993 to 2012. We used hierarchical models to determine factors
      associated with tracheostomy use among MV patients. MEASUREMENTS AND MAIN
      RESULTS: We identified 1,352,432 adults who received tracheostomy from 1993 to
      2012 (9.1% of MV patients). Tracheostomy was more common in surgical patients,
      men, and racial/ethnic minorities. Age-adjusted incidence of tracheostomy
      increased by 106%, rising disproportionately to MV use. Among MV patients,
      tracheostomy rose from 6.9% in 1993 to 9.8% in 2008, and then it declined to 8.7%
      in 2012 (P < 0.0001). Increases in tracheostomy use were driven by surgical
      patients (9.5% in 1993; 15.0% in 2012; P < 0.0001), with little change among
      nonsurgical patients (5.8% in 1993; 5.9% in 2012; P < 0.0001). Over time,
      tracheostomies were performed earlier (median, 11 d in 1998; 10 d in 2012; P <
      0.0001), whereas hospital length of stay declined (median, 39 d in 1993; 26 d in
      2012; P < 0.0001), discharges to long-term facilities increased (40.1% vs. 71.9%;
      P < 0.0001), and hospital mortality declined (38.1% vs. 14.7%; P < 0.0001).
      CONCLUSIONS: Over the past two decades, tracheostomy use rose substantially in
      the United States until 2008, when use began to decline. The observed dramatic
      increase in discharge of tracheostomy patients to long-term care facilities may
      have significant implications for clinical care, healthcare costs, policy, and
      research. Future studies should include long-term facilities when analyzing
      outcomes of tracheostomy.

PMID- 25955334
TI  - Comparative analysis of type 2 diabetes-associated SNP alleles identifies allele
      specific DNA-binding proteins for the KCNQ1 locus.
AB  - Although recent genome-wide association studies (GWAS) have been extremely
      successful, it remains a big challenge to functionally annotate disease
      associated single nucleotide polymorphisms (SNPs), as the majority of these SNPs
      are located in non-coding regions of the genome. In this study, we described a
      novel strategy for identifying the proteins that bind to the SNP-containing locus
      in an allele-specific manner and successfully applied this method to SNPs in the
      type 2 diabetes mellitus susceptibility gene, potassium voltage-gated channel,
      KQT-like subfamily Q, member 1 (KCNQ1). DNA fragments encompassing SNPs, and risk
      or non-risk alleles were immobilized onto the novel nanobeads and DNA-binding
      proteins were purified from the nuclear extracts of pancreatic beta cells using
      these DNA-immobilized nanobeads. Comparative analysis of the allele-specific DNA
      binding proteins indicated that the affinities of several proteins for the
      examined SNPs differed between the alleles. Nuclear transcription factor Y (NF-Y)
      specifically bound the non-risk allele of the SNP rs2074196 region and stimulated
      the transcriptional activity of an artificial promoter containing SNP rs2074196
      in an allele-specific manner. These results suggest that SNP rs2074196 modulates
      the affinity of the locus for NF-Y and possibly induces subsequent changes in
      gene expression. The findings of this study indicate that our comparative method
      using novel nanobeads is effective for the identification of allele-specific DNA
      binding proteins, which may provide important clues for the functional impact of
      disease-associated non-coding SNPs.

PMID- 25955337
TI  - Ray David Owen (1915-2014): geneticist and immunologist. A tribute to a true
      pioneer.

PMID- 25955335
TI  - Testing treatments interactive (TTi): helping to equip the public to promote
      better research for better health care.
AB  - Testing Treatments is a book written to help everyone understand why testing
      treatments is so important, why treatment tests have to be fair, and how everyone
      can help to promote better research for better health care. The book proved to be
      very popular and its second edition has already been translated into a dozen
      languages, with more translations in the pipeline. The texts of the original
      English and all the translations are feely downloadable from Testing Treatments
      interactive at www.testingtreatments.org. The editors of all the different
      language websites have established an TTi Editorial Alliance, to share
      experiences and provide each other with mutual support. The TTi Editorial
      Alliance seeks to promote a world in which health professionals, patients and the
      public use reliable research to inform their health decisions. Its missions are
      (i) To promote a global network, involving members of the public in partnership
      with professionals, to communicate and discuss basic principles and general
      knowledge about testing treatments; (ii) to help the public increase critical
      thinking and skills in accessing, apprehending, appraising and using research
      evidence; and (iii) to help patients and the public to participate more actively
      in health research. 

PMID- 25955338
TI  - Tumors and transplant.

PMID- 25955339
TI  - Financial and social complications as barriers to satisfaction with life among
      living kidney donors.

PMID- 25955340
TI  - Combined heart and liver transplantation against positive cross-match for patient
      with hypoplastic left heart syndrome.

PMID- 25955341
TI  - Everolimus-induced posterior reversible encephalopathy syndrome and bilateral
      optic neuropathy after kidney transplantation.

PMID- 25955342
TI  - Liver autotransplantation for an inferior vena cava tumor.

PMID- 25955343
TI  - Central retinal vein occlusion-associated tacrolimus after liver transplantation.

PMID- 25955344
TI  - Allogeneic Hematopoietic Cell Transplantation for GATA2 Deficiency in a Patient
      With Disseminated Human Papillomavirus Disease.

PMID- 25955345
TI  - Single kidneys transplanted from small pediatric donors less than 15 kilograms
      into pediatric recipients.

PMID- 25955347
TI  - Effect of sodium/iodide symporter (NIS)-mediated radioiodine therapy on estrogen
      receptor-negative breast cancer.
AB  - Since the sodium/iodide symporter (NIS) stimulates the iodine uptake in normal
      lactating breast, our study aimed to study the effect of NIS-mediated radioiodide
      therapy on ER-negative breast cancers. A recombinant lentivirus plasmid encoding
      the human NIS (hNIS) gene and firefly luciferase (Fluc) was constructed. MDA-MB
      231 cells were transfected with the recombinant lentivirus, and the hNIS gene
      expression was identified by western blot analysis and real-time PCR. Tissue
      specific expression of the NIS gene was confirmed by immunohistochemical (IHC)
      staining. Functional NIS activity in the MDA-hNIS cells was confirmed by the
      uptake of 131I and cytotoxicity assays. The relative expression level of hNIS
      mRNA exhibited a 10-fold higher expression in the MDA-hNIS cells compared with
      the level in the control cells without the endogenous NIS gene. Abundant
      expression of hNIS protein was noted in the cell membrane compared to the
      cytoplasm which confirmed the efficient expression of the functional hNIS gene.
      Iodine uptake into the MDA-hNIS cells was rapid, reaching a maximum after 15 min,
      followed by a decline. Exposure of the MDA-hNIS cells with 131I resulted in a
      time-dependent reduction in colony formation compared with the survival of the
      control (MDA) cells. Our results confirmed that NIS overexpression enhances the
      sensitivity of ER-negative breast cancer cells to radioiodide therapy.

PMID- 25955346
TI  - Transportation of Aspergillus nidulans Class III and V Chitin Synthases to the
      Hyphal Tips Depends on Conventional Kinesin.
AB  - Cell wall formation and maintenance are crucial for hyphal morphogenesis. In many
      filamentous fungi, chitin is one of the main structural components of the cell
      wall. Aspergillus nidulans ChsB, a chitin synthase, and CsmA, a chitin synthase
      with a myosin motor-like domain (MMD) at its N-terminus, both localize
      predominantly at the hyphal tip regions and at forming septa. ChsB and CsmA play
      crucial roles in polarized hyphal growth in A. nidulans. In this study, we
      investigated the mechanism by which CsmA and ChsB accumulate at the hyphal tip in
      living hyphae. Deletion of kinA, a gene encoding conventional kinesin (kinesin
      1), impaired the localization of GFP-CsmA and GFP-ChsB at the hyphal tips. The
      transport frequency of GFP-CsmA and GFP-ChsB in both anterograde and retrograde
      direction appeared lower in the kinA-deletion strain compared to wild type,
      although the velocities of the movements were comparable. Co-localization of GFP
      ChsB and GFP-CsmA with mRFP1-KinArigor, a KinA mutant that binds to microtubules
      but does not move along them, was observed in the posterior of the hyphal tip
      regions. KinA co-immunoprecipitated with ChsB and CsmA. Co-localization and
      association of CsmA with KinA did not depend on the MMD. These findings indicate
      that ChsB and CsmA are transported along microtubules to the subapical region by
      KinA. 

PMID- 25955348
TI  - Minocycline attenuates pain by inhibiting spinal microglia activation in diabetic
      rats.
AB  - The mechanisms associated with diabetes-induced neuropathic pain are complex and
      poorly understood. In order to understand the involvement of spinal microglia
      activity in diabetic pain, the present study investigated whether minocycline
      treatment is able to attenuate diabetic pain using a rat model. Diabetes was
      induced using a single intraperitoneal injection of streptozotocin (STZ).
      Minocycline was then intrathecally administered to the rats. Paw withdrawal
      threshold (PWT) and paw withdrawal latency (PWL) were tested weekly. The
      expression of OX-42, Iba-1, phospho-p38 mitogen-activated protein kinase (MAPK),
      tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and
      inducible nitric oxide synthase (iNOS), were examined in the spinal cord in order
      to evaluate the activation of microglia. The present study demonstrated that rats
      with STZ-induced diabetes exhibited increased mean plasma glucose concentration,
      decreased mean body weight and significant pain hypersensitivity compared with
      control rats. PWT and PWL values of rats with STZ-induced diabetes increased
      following treatment with minocycline. No differences were observed in expression
      levels of the microglial activity markers (OX-42, Iba-1 and phospho-p38 MAPK)
      between rats with STZ-induced diabetes and control rats. However, TNF-alpha, IL
      1beta and iNOS expression levels were higher in rats with STZ-induced diabetes
      compared with control rats. Following treatment with minocycline markers of
      microglial activation, including cytokines and iNOS, were downregulated in rats
      with STZ-induced diabetes. The results of the present study indicated that
      minocycline treatment may inhibit spinal microglial activation and attenuate
      diabetic pain in rats with STZ-induced diabetes.

PMID- 25955349
TI  - Post-tooth extraction bacteraemia: a randomized clinical trial on the efficacy of
      chlorhexidine prophylaxis.
AB  - OBJECTIVES: To investigate the development of post-extraction bacteraemia (PEB)
      after the prophylactic use of chlorhexidine (CHX). PATIENTS AND METHODS: A total
      of 201 patients who underwent a tooth extraction were randomly distributed into
      four groups: 52 received no prophylaxis (CONTROL), 50 did a mouthwash with 0.2%
      CHX before the tooth extraction (CHX-MW), 51 did a mouthwash with 0.2% CHX and a
      subgingival irrigation with 1% CHX (CHX-MW/SUB_IR) and 48 did a mouthwash with
      0.2% CHX and a continuous supragingival irrigation with 1% CHX (CHX-MW/SUPRA_IR).
      Peripheral venous blood samples were collected at baseline, 30 seconds after
      performing the mouthwash and the subgingival or supragingival irrigation, and at
      30 seconds and 15 minutes after completion of the tooth extraction. Blood samples
      were analysed applying conventional microbiological cultures under aerobic and
      anaerobic conditions performing bacterial identification of the isolates.
      RESULTS: The prevalences of PEB in the CONTROL, CHX-MW, CHX-MW/SUB_IR and CHX
      MWSUPRA_IR groups were 52%, 50%, 55% and 50%, respectively, at 30 seconds and
      23%, 4%, 10% and 27%, respectively, at 15 minutes. The prevalence of PEB at 15
      minutes was significantly higher in the CONTROL group than in the CHX-MW group
      (23% versus 4%; p = 0.005). At the same time, no differences were found between
      CONTROL group and CHX-MW/SUB_IR or CHX-MW/SUPRA_IR groups. Streptococci (mostly
      viridans group streptococci) were the most frequently identified bacteria (69
      79%). CONCLUSIONS: Performing a 0.2% CHX mouthwash significantly reduces the
      duration of PEB. Subgingival irrigation with 1% CHX didn't increase the efficacy
      of the mouthwash while supragingival irrigation even decreased this efficacy,
      probably due to the influence of these maneuvers on the onset of bacteraemia.
      CLINICAL RELEVANCE: These results confirm the suitability of performing a
      mouthwash with 0.2% CHX before tooth extractions in order to reduce the duration
      of PEB. This practice should perhaps be extended to all dental manipulations.
      TRIAL REGISTRATION: Clinicaltrials.gov NCT02150031.

PMID- 25955350
TI  - High-sensitivity cardiac troponin T in stable patients undergoing pharmacological
      stress testing.
AB  - BACKGROUND: Acute changes in high-sensitivity troponin T (hs-TnT) are induced by
      myocardial ischemia during exercise stress testing, but there are no reports of
      pharmacological stress testing. HYPOTHESIS: The pattern of troponin release by
      myocardial ischemia-induced pharmacological stress testing differs according to
      the ischemic burden in stable patients. METHODS: In total, 250 patients with
      suspected coronary artery disease underwent pharmacological stress magnetic
      resonance imaging (MRI). The amount and degree of myocardial ischemia on MRI and
      ischemic outcomes at 6 months were determined. hs-TnT levels were measured at
      baseline and 1 and 3 hours after testing. The 6-month clinical outcome was
      prespecified. RESULTS: Fifty-one patients had moderate to severe myocardial
      ischemia (group A), and 199 patients had no or mild myocardial ischemia (group
      B). hs-TnT levels were significantly higher in group A than B at baseline (11 vs
      8 pg/mL, P = 0.016) and at 1 hour (12 vs 8 pg/mL, P = 0.009) and 3 hours after
      testing (12 vs 9 pg/mL, P = 0.012). Baseline hs-TnT levels of >=14 pg/mL showed a
      43% sensitivity and 77% specificity in predicting moderate to severe ischemia by
      MRI (P = 0.03; area under the curve: 0.608, P = 0.017). Patients administered
      dobutamine had a higher acute change in hs-TnT levels 3 hours after testing than
      did those administered adenosine (21 vs 0 pg/mL, P < 0.001). There was a trend
      toward a higher incidence of myocardial infarction in patients with baseline hs
      TnT levels of >=14 pg/mL. CONCLUSIONS: hs-TnT levels are significantly higher in
      patients with moderate to severe than no or mild myocardial ischemia.

PMID- 25955351
TI  - Discovery of Peptide ligands for hepatic stellate cells using phage display.
AB  - Regardless of its cause, liver fibrosis is characterized by the excessive
      accumulation of extracellular matrix (ECM) in the liver. Hepatic stellate cells
      (HSCs) are the main producers responsible for the excessive production of ECM and
      profibrogenic cytokines in fibrotic liver. Therefore, development of HSC-specific
      delivery systems is essential for the success of antifibrotic agents. The
      objective of this study is to identify peptide ligands targeting the insulin-like
      growth factor 2 receptor (IGF2R), which is overexpressed on HSCs. We expect to
      use the peptide ligands for the future development of HSC-targeted drug delivery
      system. Protein- and whole cell-based phage display biopannings were conducted to
      identify phage/peptide candidates. Phage ELISA, cellular uptake, and cell
      viability assay were employed to evaluate the binding affinity and specificity of
      these peptide ligands to recombinant human IGF2R and HSCs. IGF2R siRNA was used
      to silence the IGF2R protein expression in human hepatic stellate cells (LX-2) to
      confirm the specificity of the identified peptide ligands. Among the identified
      peptide candidates, peptide-431 shows the highest binding affinity and
      specificity to recombinant human IGF2R protein and HSCs. The equilibrium
      dissociation constant (Kd) of peptide-431 is 6.19 MUM for LX-2 cells and 12.35
      MUM for rat hepatic stellate cells HSC-T6. Cellular uptake of peptide-431 in LX-2
      cells is significantly reduced after silencing IGF2R with siRNA. Peptide-431 also
      enhances the uptake of a proapoptotic peptide (KLA peptide) in LX-2 and HSC-T6
      cells, indicating that peptide-431 can be used as a targeting ligand to deliver
      antifibrotic agents into not only rat but also human HSCs. Dimerization of
      peptide-431 further increase its binding affinity to LX-2 cells by approximately
      9-fold. 

PMID- 25955352
TI  - A highly sensitive, selective ratiometric fluorescent probe for cobalt(II) and
      its applications for biological imaging.
AB  - Probe has been developed as the first ratiometric fluorescent cobalt probe with
      high sensitivity and selectivity based on internal charge transfer (ICT). Most
      importantly, the probe achieved the imaging and detection of cobalt in cells with
      ratiometric measurement. 

PMID- 25955353
TI  - Non-volatile Clocked Spin Wave Interconnect for Beyond-CMOS Nanomagnet Pipelines.
AB  - The possibility of using spin waves for information transmission and processing
      has been an area of active research due to the unique ability to manipulate the
      amplitude and phase of the spin waves for building complex logic circuits with
      less physical resources and low power consumption. Previous proposals on spin
      wave logic circuits have suggested the idea of utilizing the magneto-electric
      effect for spin wave amplification and amplitude- or phase-dependent switching of
      magneto-electric cells. Here, we propose a comprehensive scheme for building a
      clocked non-volatile spin wave device by introducing a charge-to-spin converter
      that translates information from electrical domain to spin domain, magneto
      electric spin wave repeaters that operate in three different regimes--spin wave
      transmitter, non-volatile memory and spin wave detector, and a novel clocking
      scheme that ensures sequential transmission of information and non-reciprocity.
      The proposed device satisfies the five essential requirements for logic
      application: nonlinearity, amplification, concatenability, feedback prevention,
      and complete set of Boolean operations.

PMID- 25955354
TI  - CRISPR screen: a high-throughput approach for cancer genetic research.

PMID- 25955355
TI  - Smoothing of contact lines in spreading droplets by trisiloxane surfactants and
      its relevance for superspreading.
AB  - Superspreading, the greatly enhanced spreading of aqueous solutions of
      trisiloxane surfactants on hydrophobic substrates, is of great interest in
      fundamental physics and technical applications. Despite numerous studies in the
      last 20 years, the superspreading mechanism is still not well understood, largely
      because the molecular scale cannot be resolved appropriately either
      experimentally or using continuum simulations. The absence of molecular-scale
      knowledge has led to a series of conflicting hypotheses based on different
      assumptions of surfactant behavior. We report a series of large-scale molecular
      dynamics simulations of aqueous solutions of superspreading and non
      superspreading surfactants on different substrates. We find that the transition
      from the liquid-vapor to the solid-liquid interface is smooth for superspreading
      conditions, allowing direct adsorption through the contact line. This finding
      complements a study [Karapetsas et al., J. Fluid Mech., 2011, 670, 5-37], which
      predicts that superspreading can occur if this adsorption path is possible. Based
      on the observed mechanism, we provide plausible explanations for the influence of
      the substrate hydrophobicity, the surfactant chain length, and the surfactant
      concentration on the superspreading phenomenon. We also briefly address that the
      observed droplet shape is a mechanism to overcome the Huh-Scriven paradox of
      infinite viscous dissipation at the contact line. 

PMID- 25955357
TI  - Correction: The role of polymerase chain reaction of high-risk human papilloma
      virus in the screening of high-grade squamous intraepithelial lesions in the anal
      mucosa of human immunodeficiency virus-positive males having sex with males.

PMID- 25955356
TI  - Identification of a new genomic hot spot of evolutionary diversification of
      protein function.
AB  - Establishment of phylogenetic relationships remains a challenging task because it
      is based on computational analysis of genomic hot spots that display species
      specific sequence variations. Here, we identify a species-specific thymine-to
      guanine sequence variation in the Glrb gene which gives rise to species-specific
      splice donor sites in the Glrb genes of mouse and bushbaby. The resulting splice
      insert in the receptor for the inhibitory neurotransmitter glycine (GlyR) conveys
      synaptic receptor clustering and specific association with a particular synaptic
      plasticity-related splice variant of the postsynaptic scaffold protein gephyrin.
      This study identifies a new genomic hot spot which contributes to phylogenetic
      diversification of protein function and advances our understanding of
      phylogenetic relationships. 

PMID- 25955358
TI  - Correction: A bioartificial renal tubule device embedding human renal
      stem/progenitor cells.

PMID- 25955360
TI  - Extracorporeal lithotripsy in patients with hemophilia: systematic review.
AB  - BACKGROUND: The management of urolithiasis in patients with haemophilia poses a
      real challenge to the urologist. AIM: We conducted a systematic literature review
      to assess the safety and efficacy of extracorporeal shock wave lithotripsy (ESWL)
      in the treatment of urolithiasis in hemophiliacs. METHODS: A systematic review
      was conducted by using the National Library of Medicine (PubMed) search engine
      between January 1985 and June 2013. We've used these key words: "haemophilia" and
      "extracorporeal shock wave lithotripsy". All articles dealing with the treatment
      of nephrolithiasis by ESWL in patients with hemophilia were included. Two
      independent reviewers extracted the data from each article. The data was included
      into a systematic review and analyzed. RESULTS: A total of 12 medical articles
      were selected with a total of 25 patients. The stone size varies from 6 to 21 mm.
      The substitution of the deficient clotting factor started the day before the
      ESWL. ESWL was effective in all patients except one after 1-6 sessions / patient.
      An ultrasound was performed after the procedure to look for potential bleeding
      complications. The judgment of the substitution therapy depends on the patient's
      condition, the presence of hematuria and the absence of signs of bleeding. Major
      bleeding complications were observed in 4 patients. CONCLUSIONS: With effective
      substitution of deficient clotting factors, ESWL is a safe and low morbidity
      method in the treatment of urinary calculi in hemophiliacs.

PMID- 25955361
TI  - [Methylene blue dye during lymphadenectomy under local anesthesia].

PMID- 25955359
TI  - Sutureless fixation of amniotic membrane for therapy of ocular surface disorders.
AB  - Amniotic membrane is applied to the diseased ocular surface to stimulate wound
      healing and tissue repair, because it releases supportive growth factors and
      cytokines. These effects fade within about a week after application,
      necessitating repeated application. Generally, amniotic membrane is fixed with
      sutures to the ocular surface, but surgical intervention at the inflamed or
      diseased site can be detrimental. Therefore, we have developed a system for the
      mounting of amniotic membrane between two rings for application to a diseased
      ocular surface without surgical intervention (sutureless amniotic membrane
      transplantation). With this system, AmnioClip, amniotic membrane can be applied
      like a large contact lens. First prototypes were tested in an experiment on
      oneself for wearing comfort. The final system was tested on 7 patients in a pilot
      study. A possible influence of the ring system on the biological effects of
      amniotic membrane was analyzed by histochemistry and by analyzing the expression
      of vascular endothelial growth factor-A (VEGF-A), hepatocyte growth factor (HGF),
      fibroblast growth factor 2 (FGF 2) and pigment epithelium-derived factor (PEDF)
      from amniotic membranes before and after therapeutic application. The final
      product, AmnioClip, showed good tolerance and did not impair the biological
      effects of amniotic membrane. VEGF-A and PEDF mRNA was expressed in amniotic
      membrane after storage and mounting before transplantation, but was undetectable
      after a 7-day application period. Consequently, transplantation of amniotic
      membranes with AmnioClip provides a sutureless and hence improved therapeutic
      strategy for corneal surface disorders.Trial Registration:ClinicalTrials.gov
      NCT02168790

PMID- 25955362
TI  - [Solitary rectal ulcer syndrome. A Tunisian monocentric Survey].
AB  - BACKGROUND: Solitary rectal ulcer syndrome is an uncommon and benign defecation
      disorder. Occidental series are scarce and to our knowledge, Tunisian data are
      not available. AIMS: The aim of this study was to evaluate the clinical,
      endoscopic and histological spectrum of the solitary rectal ulcer syndrome.
      METHODS: All the patients diagnosed with solitary rectal ulcer syndrome from
      January 2001 to 2012 were included in the study. The medical records were
      reviewed retrospectively to evaluate the clinical spectrum of the patients along
      with the endoscopic, histological and therapeutic findings. RESULTS: A total of
      15 patients were evaluated: 7 males; mean age 42.6 years. Bleeding per rectum was
      present in 66% and dyschezia in 73%. Endoscopically, solitary lesion was present
      in 66% patients. The most frequent dynamic abnormalities shown by defecography
      were of rectal intussusception (53%). Anorectal manometry was performed in seven
      cases disclosing dyssynergia in 2 cases. Thirty patients underwent surgery,
      always after failure of medical treatment and one patient was treated with
      biofeedback. Rectopexy was the most utilized technic. After a mean follow-up of
      29 months, total regression of symptoms was noted in 50% of patients who
      underwent surgery. CONCLUSION: In this cohort, diagnostic and therapeutic
      spectrum of solitary rectal ulcer syndrome was comparable to occidental features.
      Nevertheless, accesses to manometry and defecography as well as biofeedback were
      limited.

PMID- 25955363
TI  - [Prognostic factors in metastatic colorectal cancer in Tunisia: A retrospective
      study of 130 patients].
AB  - BACKGROUND: The survival of patients with a metastatic colon cancer has improved
      with palliative chemotherapy, targeted therapies and surgery. Several prognostic
      factors influencing the survival of these patients were identified in the
      literature represented mainly by clinical factors: general condition, number and
      site of metastases, rate of white blood cells, initial carcinoembryonic antigen
      (CEA) rate, hemoglobin level, and therapeutic factors mainly represented by
      resection of metastases. AIM: To evaluate within a Tunisian retrospective study
      the significant prognostic factors on survival of metastatic colorectal cancer
      (MCRC). METHODS: We collected retrospectively 130 patients with MCRC treated in
      Sfax from january 2000 to December 2007. Uni and multivariate analysis were
      performed according to cox model for the following factors : Age or > 40 years,
      gender, synchronous vs metachronous metastases, disease-free survival (DFI) 1 >
      1year, tumor site(colon vs rectum), performance status or PS ( 0-1or 2-3), white
      blood cells count (< or > 103/ml3 , haemoglobin rate (Hb) or > 11g/dl, seric
      carcinoembryonic antigen rate (CEA) < vs > 10 ng/ml, number of metastatic sites
      (single vs multiple), site of metastatic site (liver vs extrahepatic) and
      resection or not of the metastatic localizations. RESULTS: Statistical analysis
      showed for univariate analysis the positive impact of : PS 1, (Hb) rate > 11
      g/dl, CEA) < 10 ng/ml and resection of metastases, while in in multivariate
      analysis, they were : a good PS and Hb > 11 g/dl. CONCLUSION: Our retrospective
      study confirmed the known prognostic impact of simple clinical tools like a good
      performance Status and Hb > 11 g/dl, a (CEA) rate lower than 10 ng/ml and
      resection of metastases which were identified by several other series such as
      predictive factors of a better survival in patients with metastatic colorectal
      cancer.

PMID- 25955364
TI  - Anatomical variations of renal venous vascularisation. A study of 71 three
      dimensional kidney endocasts.
AB  - BACKGROUND: A better understanding of the anatomy of the renal vein and its
      relationship with the arterial and excretory systems can prevent intra operative
      complications. METHODS: Three-dimensional endocasts of intrarenal vessels and
      renal collecting systems were obtained from fresh cadavers, by injecting a
      polyester resin coloured with different pigments. A total of 71 endocasts were
      studied: 37 right kidneys and 34 left kidneys. RESULTS: Renal vein was unique in
      88% of cases and double in 11% of cases. It was formed in 52% of cases by 3
      trunks. Intrarenal veins anastomosed together to form 2 levels of arcades in 28%
      of cases and 3 levels in 71% of cases. The venous drainage of the upper pole was
      provided by two anterior and posterior plexus in 38% of cases, and by a single
      anterior plexus in 61% of cases. In 22% of cases, the venous drainage of the
      lower pole was provided by both an anterior and a posterior plexus, and in 77% of
      cases, there was only an anterior plexus. Renal artery was posterior to the vein
      in 66% of cases. It was anterior to the vein in 29% of cases, and located
      directly above it in 4% of cases. In 60% of cases, we noted a close relationship
      between the anterior surface of the ureteropelvic junction and the lower branch
      of the renal vein. CONCLUSION: Venous vascularisation of the kidney appears to be
      variable and its relationship with the arterial and the excretory systems may be
      complex.

PMID- 25955365
TI  - [Predictors of smoking relapse among adult in smoking cessation].
AB  - BACKGROUND: Smoking is a public health problem in Tunisia. The smoking cessation
      assistance is one of means against this epidemic. Few smokers require this need
      to quit. PURPOSE: this study aimed at identifying the predictive factors
      associated to the smoking relapse at the adult. METHOD: We carried out a
      prospective cohort study, during a period of 18 months, at the smoking cessation
      center of the University hospital of Monastir (Tunisia). The population study
      consisted of adult abstinent in smoking cessation interventions. Baseline
      contained a questionnaire investigating the smoking history, the nicotine
      dependence and the anxiety / depression state and information of the medical
      examination at follow-up visits. A phone survey was realized, 21 months after the
      inclusion beginning, to estimate the rate of smoking abstinence, the deadline
      average of relapse and these predictors. A multivariate Cox regression was used
      to identify predictors of smoking relapses. RESULTS: A total of 143 adults were
      included in our study with a mean age of 44 +/- 14 years. The median consumption
      was 30 cigarettes/ day. The median of initial carbon monoxide expired was 13 ppm.
      The median period of the medical treatment was 4 weeks. In the survey 74 patients
      relapse (51,7%) : IC95% [44 -60], with a median deadline of relapse of 11 weeks
      IC95% [9,1-12,9]. In the multivariate analysis, smoking relapse was associated
      with a period of treatment less than 4 weeks OR: 2,53: IC95 [1,48-4,32], and with
      a perception, less than 2 benefits, at the medical examination at follow-up
      visits OR: 1,54: IC95 [1,02-2,66]. CONCLUSION: The results of this study give us
      important clarifications, on profits offered by the adult smoking cessation
      interventions.

PMID- 25955366
TI  - Baseline characteristics of a school based intervention to prevent non
      communicable diseases risk factors: Project "together in Health".
AB  - BACKGROUND: Tobacco use, unhealthy diet, and physical inactivity are among the
      leading causes of the major non communicable diseases. So, prevention should take
      place early in childhood. AIM: In this paper, we will present an overview of
      project "Together in health" in schools, a component of a community based
      intervention. It consists on a school based intervention with the aim to improve
      knowledge, attitudes and behaviors concerning the main chronic disease risk
      factors such as unhealthy diet, physical inactivity and smoking. METHODS: We
      conducted a quasi experimental design with intervention and control groups. The
      study concerned pupils of colleges of Sousse aged 11 to 16 years old in 7th and
      9th grade. The pre-assessment concerned a randomized sample of schoolchildren.
      The proportional and stratified sample was composed of 4003 schoolchildren with
      1929 and 2074 respectively in intervention and control groups. We used chi square
      test to compare percentages with 0.05 level of significance. RESULTS: The sex
      ration was been 1 in the intervention group and 0.87 in control group. The mean
      age of our population was been 13.48+/-1.29 and 13.24+/-1.25 respectively in
      intervention and control groups with significant difference (p<10-3).
      Schoolchildren who reported practicing physical activity daily represented 19.1%
      and 12.7% respectively in intervention and control groups. Concerning eating
      habits, the schoolchildren reported frequency (number of days per week) of
      consuming various foods and beverages included respectively in the intervention
      and control group: vegetables 3.9 days/week and 4.81 days/week, fruits 5.41
      days/week and 5.7 days/week, high fat food 2.49 days/week and 2.48 days/week,
      sweetened beverage 3.84 days/week and 3.3 days/week, sweets 4.33 days/week and
      4.57 days/week. The proportion of irregular smokers was been respectively 6.8%
      and 2.2% among boys and girls in the intervention group and 11.3% and 0.9% in
      control group. CONCLUSION: Integrated and sustainable interventions against non
      communicable disease risk factors in this region are needed to prevent these
      diseases early in childhood.

PMID- 25955367
TI  - [High risk areas for echinococcosis-hydatidosis in Tunisia].
AB  - AIM: The study was conducted in order to identify high risk areas for hydatidosis
      in Tunisia witch would be eligible for a Hydatidosis control program initiation.
      METHODS: The most recent epidemiological investigation on surgical incidence of
      hydatidosis was used to classify governorates according to their incidence rate.
      A "global hydatidosis risk score" was calculated for each governorate, combining
      some parameters related to the hygiene conditions of the population, the literacy
      rate, the canine density and livestock census. Spearman correlation coefficient
      was used to compare scores and surgical incidences. Mapping analysis has been
      conducted. The surgical incidence rate of hydatidosis classifies each governorate
      regarding occurrence of human cases. The global hydatidosis risk score, by
      governorate, pointed out the most exposed areas to the disease. RESULTS: The
      mapping analysis showed a good agreement between the incidence rate of the
      disease and the global hydatidosis risk score and made it possible to identify
      the population of the center and the west of the country as a most exposed
      population for the diseases. CONCLUSION: In order to have a chance for
      implementation, hydatidosis control program should target the three jointed
      governorates of Kasserine, Siliana and Kef, which have the highest incidence
      rates and the worst scores.

PMID- 25955368
TI  - [Characteristics of deep vein thrombosis in the elderly].
AB  - PURPOSE OF THE STUDY: Deep vein thrombosis is a common condition in geriatric.
      The identification of risk factors for venous thrombosis in the elderly is
      important because it allows an appropriate prescription of preventive treatments.
      The purpose of this study is to identify the etiologic and therapeutic
      characteristics of deep vein thrombosis of the lower limbs in the elderly.
      PATIENTS AND METHODS: A retrospective study of 155 patients with lower limb deep
      vein thrombosis confirmed by venous Doppler. These patients were divided into two
      groups: group 1 (patients aged 65 years or more) and group 2 (patients whose age
      was below 65 years). A comparison between these two groups was performed.
      RESULTS: The average age of patients in group 1 was 74.89 years (+/- 6.43). The
      sex ratio in this group was 0.68. The thrombosis was more frequently proximal in
      patients of group 1. Patients of group 1 had significantly more risk factors than
      those of group 2 (p <0.05). Among risk factors studied, only the cancers were
      significantly more frequent in group 1 (p = 0.002). The frequency of hemorrhagic
      events in both groups was comparable but bleeding was more common in patients of
      group 1 with cancer. CONCLUSION: Our study confirms the multifactorial origin of
      deep vein thrombosis in the elderly and the incidence of malignant etiology. The
      results of this study also call for vigilance in the use of anticoagulants in the
      elderly especially in the presence of cancer because it is an additional risk
      factor for bleeding.

PMID- 25955369
TI  - Urethritis due to corynebacterium striatum: An emerging germ.
AB  - Corynedbacterium striatum (CS) is a Gram-positive coryneform bacillus that is
      part of mucous and skin flora. It has been considered as a causative agent of
      many infections in intensive care, neurology, traumatology and urology, but was
      never implicated in non-gonococcal urethritis. We report the case of a nosocomial
      urethritis due to Corynebacterium striatum following resection of an intrameatus
      condyloma.

PMID- 25955371
TI  - Locked in syndrome revealing an antiphospholipid syndrome.

PMID- 25955370
TI  - Epidural hematoma due to spinal epidural anaesthesia.

PMID- 25955372
TI  - Aneurysm of the hepatic artery : An exceptional association with the polycystic
      hepatorenal disease.

PMID- 25955373
TI  - Tumeur neuro-ectodermique primitive du poumon chez un homme de 60 ans.

PMID- 25955374
TI  - About an unusual association of Guillan Barre syndrome and pulmonary
      tuberculosis.

PMID- 25955375
TI  - Association of Crohn's disease and appendiceal carcinoid tumor: Report of two
      cases.

PMID- 25955376
TI  - Spigelian hernia and crypthorchidism: Another piece to the puzzle.

PMID- 25955377
TI  - Acute flaccid quadriplegia in rheumatoid arthritis.

PMID- 25955378
TI  - Hypertensive retinopathy revealing a pheochromocytoma associated with a liver
      hydatid cyst in a child.

PMID- 25955379
TI  - A case of primary non-hodgkin's lymphoma of skeletal muscle in exceptional
      location at the left shoulder.

PMID- 25955380
TI  - Eagle's syndrome revealed by swallowing disorders: A case report.

PMID- 25955381
TI  - A liquid chromatography with tandem mass spectrometry method for simultaneous
      determination of UTL-5g and its metabolites in human plasma.
AB  - UTL-5g is a novel small-molecule TNF-alpha inhibitor under investigation as both
      a chemoprotective and radioprotective agent. Animal studies showed that
      pretreatment of UTL-5g protected kidney, liver, and platelets from cisplatin
      induced toxicity. In addition, UTL-5g reduced liver and lung injuries induced by
      radiation in vivo. Although a number of preclinical studies have been conducted,
      a validated bioanalytical method for UTL-5g in human plasma has not been
      published. In this work, a sensitive and reproducible reverse-phase liquid
      chromatography coupled to tandem mass spectrometry (LC-MS/MS) assay was developed
      and validated for the determination of UTL-5g and its metabolites, 5
      methylisoxazole-3-carboxylic acid (ISOX) and 2,4-dichloroaniline (DCA), in human
      plasma. The method involves a simple methanol precipitation step followed by
      injection of the supernatant onto a Waters 2695 HPLC system coupled with a Waters
      Quattro MicroTM triple quadrupole mass spectrometer. Chromatographic separation
      was accomplished using a Waters Nova-Pak C18 column maintained at 30 degrees C,
      running at gradient mode with mobile phase consisting of 0.1% formic acid in
      water and 0.1% formic acid in methanol at a flow rate of 0.2mL/min. The analytes
      were monitored under positive electrospray ionization (ESI). Quantitation of
      these compounds in plasma was linear from 0.05 to 10MUM. The lower limit of
      quantitation (LLOQ) was 0.05, 0.1, and 0.2MUM for UTL-5g, ISOX and DCA,
      respectively. The accuracy and intra-and inter-day precisions were within the
      generally accepted criteria for bioanalytical method (<15%). This method provides
      a practical tool to measure and characterize the plasma concentration-time
      profiles for UTL-5g and its metabolites, ISOX and DCA. 

PMID- 25955382
TI  - Chromatographic separation of PTAD-derivatized 25-hydroxyvitamin D3 and its C-3
      epimer from human serum and murine skin.
AB  - The detection of 25-hydroxyvitamin D at low levels in biological samples is
      facilitated by the use of chemical derivatization with 4-phenyl-1,2,4-triazoline
      3,5-dione (PTAD) in concert with liquid chromatography-tandem mass spectrometry
      (LC-MS/MS). This mode of analysis is notably hampered by chromatographic co
      elution of 25-hydroxyvitamin D3 (25OHD3) and its C-3 epimer (C3epi). The
      objective of this work was to improve upon current LC-MS/MS methods used for the
      analysis of PTAD-derivatized 25-hydroxyvitamin D3 by resolving it from C3epi.
      Additionally, the applicability of this method in human serum and murine skin was
      investigated. C18 columns of increasing length and varying particle sizes were
      assessed for performance using a mixed standard of PTAD-derivatized 25OHD3 and
      C3epi. Serum samples were processed using solid phase extraction, and skin was
      powdered and extracted for lipophilic compounds. The samples were derivatized
      with PTAD and subsequently analyzed using isotope dilution LC-MS/MS with
      atmospheric pressure chemical ionization operated in positive mode. Near baseline
      resolution of PTAD-25OHD3 from PTAD-C3epi was achieved on a 250mm C18 column with
      3MUm sized particles. This separation allowed for detection and quantification of
      both metabolites in serum and skin samples. PTAD-C3epi represented a significant
      confounding analyte in all samples, and comprised up to 20% of the status
      measurement in skin. This method is a significant improvement on the
      chromatography of PTAD-derivatized vitamin D metabolites that could greatly
      influence the assessment of vitamin D status and C3epi biology in low abundance
      samples. 

PMID- 25955383
TI  - Radiotherapy treatment for nonmelanoma skin cancer.
AB  - Non-melanoma skin cancer is the most common malignancy in the USA, with an
      estimated 3.5 million cases per year. Treatment options include surgical
      excision, radiation therapy (RT), photodynamic therapy and topical agents.
      Although surgical excision remains the mainstay of therapy, RT offers an
      effective alternative. RT can be used as an adjunct to surgery in high-risk
      situations, or in cases where surgical excision would lead to impaired cosmesis
      and/or functional outcomes. Radiation treatment modalities for non-melanoma skin
      cancers are diverse. Studies in the literature have examined the clinical effects
      of a wide variety of modalities, areas of the body and dosages. The most common
      modalities include superficial or orthovoltage RT, electron beam therapy and high
      dose-rate brachytherapy. This article aims to review the diverse radiotherapy
      treatment modalities for non-melanoma skin cancers, focusing on tumor control and
      toxicity. 

PMID- 25955384
TI  - Chasing the Origin of Viruses: Capsid-Forming Genes as a Life-Saving
      Preadaptation within a Community of Early Replicators.
AB  - Virus capsids mediate the transfer of viral genetic information from one cell to
      another, thus the origin of the first viruses arguably coincides with the origin
      of the viral capsid. Capsid genes are evolutionarily ancient and their emergence
      potentially predated even the origin of first free-living cells. But does the
      origin of the capsid coincide with the origin of viruses, or is it possible that
      capsid-like functionalities emerged before the appearance of true viral entities?
      We set to investigate this question by using a computational simulator comprising
      primitive replicators and replication parasites within a compartment matrix. We
      observe that systems with no horizontal gene transfer between compartments
      collapse due to the rapidly emerging replication parasites. However, introduction
      of capsid-like genes that induce the movement of randomly selected genes from one
      compartment to another rescues life by providing the non-parasitic replicators a
      mean to escape their current compartments before the emergence of replication
      parasites. Capsid-forming genes can mediate the establishment of a stable meta
      population where parasites cause only local tragedies but cannot overtake the
      whole community. The long-term survival of replicators is dependent on the
      frequency of horizontal transfer events, as systems with either too much or too
      little genetic exchange are doomed to succumb to replication-parasites. This
      study provides a possible scenario for explaining the origin of viral capsids
      before the emergence of genuine viruses: in the absence of other means of
      horizontal gene transfer between compartments, evolution of capsid-like
      functionalities may have been necessary for early life to prevail. 

PMID- 25955385
TI  - Mechanisms Underlying the Scratching Behavior Induced by the Activation of
      Proteinase-Activated Receptor-4 in Mice.
AB  - A role for proteinase-activated receptor-4 (PAR-4) was recently suggested in itch
      sensation. Here, we investigated the mechanisms underlying the pruriceptive
      actions of the selective PAR-4 agonist AYPGKF-NH2 (AYP) in mice. Dorsal
      intradermal (i.d.) administration of AYP elicited intense scratching behavior in
      mice, which was prevented by the selective PAR-4 antagonist (pepducin P4pal-10).
      PAR-4 was found to be coexpressed in 32% of tryptase-positive skin mast cells,
      and AYP caused a 2-fold increase in mast cell degranulation. However, neither the
      treatment with cromolyn nor the deficiency of mast cells (WBB6F1-Kit(W/Wv) mice)
      was able to affect AYP-induced itch. PAR-4 was also found on gastrin-releasing
      peptide (GRP)-positive neurons (pruriceptive fibers), and AYP-induced itch was
      reduced by the selective GRP receptor antagonist RC-3095. In addition, AYP evoked
      calcium influx in ~1.5% of cultured DRG neurons also sensitive to TRPV1
      (capsaicin) and/or TRPA1 (AITC) agonists. Importantly, AYP-induced itch was
      reduced by treatment with either the selective TRPV1 (SB366791), TRPA1 (HC
      030031), or NK1 (FK888) receptor antagonists. However, genetic loss of TRPV1, but
      not of TRPA1, diminished AYP-induced calcium influx in DRG neurons and the
      scratching behavior in mice. These findings provide evidence that PAR-4
      activation by AYP causes pruriceptive itch in mice via a TRPV1/TRPA1-dependent
      mechanism. 

PMID- 25955387
TI  - OsHUB1 and OsHUB2 interact with SPIN6 and form homo- and hetero-dimers in rice.
AB  - Ubiquitin-mediated protein degradation is involved in various cellular processes
      including plant-microbe interactions and defense responses. Although there are
      many E3 ubiquitin ligases in rice, the functions of their targets in defense
      responses are unclear. We recently found that SPIN6 (SPL11-interacting Protein 6)
      is a Rho GTPase-activating protein and acts as the target of the E3 ligase SPL11,
      a negative regulator of plant cell death and innate immunity. Our results showed
      that SPIN6 serves as a link between the SPL11-mediated ubiquitination pathway and
      the OsRac1-associated defense system. Here, we show that SPIN6 interacts with
      OsHUB1 and OsHUB2, the homologous proteins of Arabidopsis RING finger E3 ligases
      HUB1 and HUB2. OsHub1 and OsHub2 are down-regulated in the Spin6 RNAi plants and
      during the compatible interaction between rice and Magnaporthe oryzae. OsHub1 and
      OsHub2 are induced by hormone treatments. Like HUB1 and HUB2 in Arabidopsis,
      OsHUB1 and OsHUB2 in rice form homo- and hetero-dimers. Our results suggest that
      OsHUB1 and OsHUB2 may be associated with the SPIN6/OsRac1 pathway in rice
      immunity. 

PMID- 25955388
TI  - MicroRNA-195-5p acts as an anti-oncogene by targeting PHF19 in hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. PHD
      finger protein 19 (PHF19) encodes a member of the polycomb group (PcG) of
      proteins that functions by maintaining the repressive transcriptional states of
      many developmental regulatory genes. In addition, it has been shown that miR-195
      plays an important role in the molecular etiology of HCC; however, the effect and
      possible mechanism of PHF19 on HCC is unclear, and the association between PHF19
      and miR-195 has seldom been addressed. In the present study, we investigated the
      carcinogenic activity and mechanism of PHF19 on HCC in vivo and in vitro. Our
      results showed that PHF19 is a potential target of hsa-miR-195-5p based on a
      bioinformatic analysis and results of a luciferase reporter assay. PHF19 was
      downregulated after transfection with hsa-miR-195-5p mimics. Moreover, we
      demonstrated that overexpression of PHF19 promoted hepatoma cell migration,
      invasion and proliferation in vitro. In contrast, overexpression of hsa-miR-195
      5p in hepatoma cells reduced PHF19 expression, leading to suppression of hepatoma
      cell invasion, migration and proliferation in vitro. In addition, PHF19 markedly
      promoted the growth of xenograft tumors, while hsa-miR-195-5p markedly suppressed
      the growth of xenograft tumors in nude mice. These results provide evidence that
      PHF19 promotes HCC and is regulated by the tumor-suppressor, miR-195-5p.

PMID- 25955389
TI  - How much does a verbal autopsy based mortality surveillance system cost in rural
      India?
AB  - OBJECTIVE: This paper aims to determine the cost of establishing and sustaining a
      verbal-autopsy based mortality surveillance system in rural India. MATERIALS AND
      METHODS: Deaths occurring in 45 villages (population 185,629) were documented
      over a 4-year period from 2003-2007 by 45 non-physician healthcare workers
      (NPHWs) trained in data collection using a verbal autopsy tool. Causes of death
      were assigned by 2 physicians for the first year and by one physician for the
      subsequent years. Costs were calculated for training of interviewers and
      physicians, data collection, verbal autopsy analysis, project management and
      infrastructure. Costs were divided by the number of deaths and the population
      covered in the year. RESULTS: Verbal-autopsies were completed for 96.7% (5786) of
      all deaths (5895) recorded. The annual cost in year 1 was INR 1,133,491 (USD
      24,943) and the total cost per death was INR 757 (USD 16.66). These costs
      included training of NPHWs and physician reviewers Rs 67,025 (USD 1474), data
      collection INR 248,400 (USD 5466), dual physician review for cause of death
      assignment INR 375,000 (USD 8252), and project management INR 341,724 (USD 7520).
      The average annual cost to run the system each year was INR 822,717 (USD18104)
      and the cost per death was INR 549 (USD 12) for the next 3 years. Costs were
      reduced by using single physician review and shortened re-training sessions. The
      annual cost of running a surveillance system was INR 900,410 (USD 19814).
      DISCUSSION: This study provides detailed empirical evidence of the costs involved
      in running a mortality surveillance site using verbal-autopsy.

PMID- 25955390
TI  - Trends and regional variation in the incidence of head and neck cancers in
      England: 2002 to 2011.
AB  - Recent studies show an increased incidence of head and neck cancers worldwide.
      The present study evaluated the trend in the incidence of head and neck cancers
      in England during 2002-2011. Data were extracted from the database of Office for
      National Statistics. The study population was categorised according to age,
      residential area, gender and cancer sub-types. Overall trend in incidence of head
      and neck cancer and some subtypes were examined using Poisson regression models.
      In total, 71,457 head and neck cancers were registered in England between 2002
      and 2011 and 68% of patients were males. Statistically significant increases in
      incidence of 27.0 and 32.4% were documented in males and females, respectively
      (p<0.001) with the largest increase in the 60+ age category. Potentially HPV
      associated cancers, oral cavity cancers and laryngeal cancers increased by 47.1,
      24.1 and 1.7% in males and 37.5, 25.5 and 7.7% in females, respectively
      (p<0.001). Regional differences were also noted with the highest incidence (18.0
      and 17.0 per 100,000, respectively) in the North East and North West of England.
      Our results for England showed an increase in the incidence of both oral cavity
      and oropharyngeal cancer in both genders, whilst laryngeal cancer incidence
      remained stable. 

PMID- 25955391
TI  - Morphological Differences between Larvae of the Ciona intestinalis Species
      Complex: Hints for a Valid Taxonomic Definition of Distinct Species.
AB  - The cosmopolitan ascidian Ciona intestinalis is the most common model species of
      Tunicata, the sister-group of Vertebrata, and widely used in developmental
      biology, genomics and evolutionary studies. Recently, molecular studies suggested
      the presence of cryptic species hidden within the C. intestinalis species, namely
      C. intestinalis type A and type B. So far, no substantial morphological
      differences have been identified between individuals belonging to the two types.
      Here we present morphometric, immunohistochemical, and histological analyses, as
      well as 3-D reconstructions, of late larvae obtained by cross-fertilization
      experiments of molecularly determined type A and type B adults, sampled in
      different seasons and in four different localities. Our data point to
      quantitative and qualitative differences in the trunk shape of larvae belonging
      to the two types. In particular, type B larvae exhibit a longer pre-oral lobe,
      longer and relatively narrower total body length, and a shorter ocellus-tail
      distance than type A larvae. All these differences were found to be statistically
      significant in a Discriminant Analysis. Depending on the number of analyzed
      parameters, the obtained discriminant function was able to correctly classify >
      93% of the larvae, with the remaining misclassified larvae attributable to the
      existence of intra-type seasonal variability. No larval differences were observed
      at the level of histology and immunohistochemical localization of peripheral
      sensory neurons. We conclude that type A and type B are two distinct species that
      can be distinguished on the basis of larval morphology and molecular data. Since
      the identified larval differences appear to be valid diagnostic characters, we
      suggest to raise both types to the rank of species and to assign them distinct
      names. 

PMID- 25955393
TI  - Suppression of microRNA-18a expression inhibits invasion and promotes apoptosis
      of human trophoblast cells by targeting the estrogen receptor alpha gene.
AB  - The purpose of the present study was to gain further understanding of the
      function of microRNA-18a (miR-18a) expression in the JEG-3 human trophoblast cell
      line. JEG-3 cells were transfected with pre-miR-18a mimics or miR-18a inhibitors.
      The effects of miR-18a on trophoblast cell invasion and apoptosis, and on the
      expression of estrogen receptor alpha (ESRalpha) were analyzed using a Transwell
      invasion assay, flow cytometry, reverse transcription-polymerase chain reaction,
      western blot analysis and a luciferase assay. The results of the present study
      suggested that miR-18a expression suppression led to a decrease in JEG-3 cell
      invasion and an increase in JEG-3 cell apoptosis, by inducing ESRalpha
      expression. The present study provides evidence for the involvement of miR-18a in
      the pathogenesis of pre-eclamptic pregnancies.

PMID- 25955392
TI  - TGF-beta1 Up-Regulates Connective Tissue Growth Factor Expression in Human
      Granulosa Cells through Smad and ERK1/2 Signaling Pathways.
AB  - Connective tissue growth factor (CTGF), which is also called CCN2, is a secreted
      matricellular protein. CTGF regulates various important cellular functions by
      interacting with multiple molecules in the microenvironment. In the ovary, CTGF
      is mainly expressed in granulosa cells and involved in the regulation of
      follicular development, ovulation and luteinization. TGF-beta1 has been shown to
      up-regulate CTGF expression in rat and hen granulosa cells. However, the
      underlying molecular mechanisms of this up-regulation remain undefined. More
      importantly, whether the stimulatory effect of TGF-beta1 on CTGF expression can
      be observed in human granulosa cells remains unknown. In the present study, our
      results demonstrated that TGF-beta1 treatment up-regulates CTGF expression in
      both immortalized human granulosa cells and primary human granulosa cells. Using
      a siRNA-mediated knockdown approach and a pharmacological inhibitor, we
      demonstrated that the inhibition of Smad2, Smad3 or ERK1/2 attenuates the TGF
      beta1-induced up-regulation of CTGF. This study provides important insights into
      the molecular mechanisms that mediate TGF-beta1-up-regulated CTGF expression in
      human granulosa cells. 

PMID- 25955394
TI  - Upregulation of GRIM-19 inhibits the growth and invasion of human breast cancer
      cells.
AB  - Gene associated with retinoid-interferon (IFN)-induced mortality 19 (GRIM-19), a
      novel IFN-beta/retinoic acid-inducible gene product, has been identified as a
      potential tumor suppressor, which is associated with the inhibition of tumor
      growth. GRIM-19 has been demonstrated to be downregulated in the ovarian tissue
      of patients with breast cancer, however, its role in breast cancer remains to be
      fully elucidated. In the present study, a recombinant eukaryotic expression
      plasmid carrying GRIM-19 was constructed and then transfected into the MCF7 human
      breast cancer cell line to examine its effects on breast cancer cell growth,
      migration and invasion using several in vitro approaches. The results
      demonstrated that upregulation GRIM-19 in the MCF7 cells significantly inhibited
      cell proliferation, colony formation, migration and invasion, and induced cell
      apoptosis. Additionally, upregulation of GRIM-19 also suppressed the secretion of
      urokinase-type plasminogen activator (u-PA), matrix metalloproteinase (MMP)-2,
      MMP-9 and vascular endothelial growth factor (VEGF). It was also demonstrated
      that the activation of signal transducer and activator of transcription 3 (STAT3)
      was downregulated by the expression of GRIM-19. These results revealed that
      overexpression of the GRIM-19 gene may be an effective approach to control the
      growth and invasion of human breast cancer cells.

PMID- 25955395
TI  - First Clinical Evaluation of High-Pitch Dual-Source Computed Tomographic
      Angiography Comparing Automated Tube Potential Selection With Automated Tube
      Current Modulation.
AB  - OBJECTIVE: To investigate and compare the use of automated tube potential
      selection (ATPS) with automated tube current modulation (ATCM) in high-pitch dual
      source computed tomographic angiography (CTA) for imaging the whole aorta without
      electrocardiogram synchronization. METHODS: Two groups of 60 patients underwent
      CTA on a dual-source computed tomographic device in high-pitch mode: ATCM (with
      100-kV fixed tube potential) was used in group 1 and ATPS (with the same image
      quality options) in group 2. For the evaluation of radiation exposure, CT dose
      index and dose-length product were analyzed. Contrast and image quality were
      assessed by 2 independent observers. RESULTS: The ATPS group received a higher
      radiation dose than the ATCM group (P < 0.001) because in 80% of patients, the
      software switched to use of a 120-kV tube potential. In all cases, images of the
      aorta were of sufficient quality. CONCLUSIONS: High-pitch dual-source CTA of the
      aorta using ATPS is feasible in clinical routine, but is associated with higher
      radiation exposure than the ATCM protocol. This finding contradicts previously
      evaluations of ATPS based on single-source techniques.

PMID- 25955396
TI  - Dynamic Computed Tomographic Features of Adult Renal Cell Carcinoma Associated
      With Xp11.2 Translocation/TFE3 Gene Fusions: Comparison With Clear Cell Renal
      Cell Carcinoma.
AB  - OBJECTIVE: To investigate the dynamic contrast-enhanced computed tomography (CT)
      characteristics of renal cell carcinoma associated with Xp11.2 translocation and
      TFE gene fusion (Xp11.2 RCC) by comparison with clear cell renal cell carcinoma
      (CCRCC). METHODS: Dynamic contrast-enhanced CT images and clinical and
      pathological records of 20 adult patients with Xp11.2 RCC confirmed by TFE3
      immunohistochemical and fluorescence in situ hybridization assay were
      retrospectively analyzed and compared with the findings of 21 contemporary
      CCRCCs. RESULTS: Renal cell carcinoma associated with Xp11.2 translocation and
      TFE gene fusions often occurred in young (30.6 +/- 8.6 years) patients with
      hematuria (9/20). They presented as well-defined (17/20) cystic-solid (17/20)
      mass with hemorrhage (8/20) and circular/rim calcifications (6/20). Dynamic
      contrast-enhanced CT showed heterogeneous moderate prolonged enhancement. A tumor
      to-cortex attenuation ratio in corticomedullary phase less than 0.62 gave a
      sensitivity of 90.0% and a specificity of 92.9% in differentiating Xp11.2 RCC
      from CCRCC (area under the receiver operating characteristic curve = 0.957, P <
      0.001). CONCLUSIONS: Computed tomographic characteristics and dynamic contrast
      enhanced patterns and index can differentiate Xp11.2 RCC from CCRCC.

PMID- 25955397
TI  - Can Radiation Dose Be Reduced and Image Quality Improved With 80-kV and Dual
      Phase Scanning of the Lower Extremities With 64-Slice Computed Tomography
      Angiography?
AB  - OBJECTIVE: To prospectively compare the new computed tomographic angiography
      (CTA) protocol (NCP) using 80-kV and dual-phase scanning with the routine CTA
      protocol (RCP) using 120-kV and single-phase scanning in patients with peripheral
      arterial disease. METHODS: A total of 60 patients were randomized to undergo the
      NCP (30 patients) or RCP (30 patients) scan. We compared the arterial attenuation
      values, overriding of the contrast bolus, signal-to-noise ratio, and radiation
      dose between 2 groups. RESULTS: The occurrence rate of contrast bolus overriding
      was not statistically significant (P = 0.69). The average arterial attenuation
      value in the NCP group was significantly higher (P < 0.05) than that in the RCP
      group. The radiation dose in the RCP group was significantly higher (P < 0.001)
      than that in the NCP group. The mean signal-to-noise ratio in the NCP group was
      significantly lower (P < 0.001). CONCLUSIONS: Sixty-four-slice CTA with the NCP
      can significantly reduce the radiation dose and improve the arterial enhancement
      and calf arteries imaging.

PMID- 25955398
TI  - Additional Diagnostic Value of Inversion Recovery Single-Shot Fast-Spin Echo
      Sequence in Differentiation Between Hepatic Hemangiomas and Cysts.
AB  - OBJECTIVE: The aim of this study was to evaluate the additional diagnostic value
      of "inversion recovery" single-shot fast-spin echo (IR-SSFSE) sequence using the
      inversion time at the null point for hepatic hemangiomas as a supplement to
      standard T2-weighted (T2W) magnetic resonance imaging for the distinction of
      hemangiomas and cysts. METHODS: A total of 228 lesions in 56 patients were
      evaluated in this retrospective study. In addition to routine hepatic magnetic
      resonance imaging, IR-SSFSE imaging using inversion time value of 600
      milliseconds (null point for hepatic hemangiomas) was obtained. Two radiologists
      independently reviewed T2W images at first and T2W images plus IR-SSFSE sequence
      4 weeks afterward and used a 5-point scale to indicate the possibility of
      detected hyperintense lesion is a cyst or a hemangioma. A receiver operating
      characteristic analysis and kappa statistics were used to evaluate the diagnostic
      additive value of IR-SSFSE sequence for differentiation of hepatic hemangiomas
      and cysts, and to determine interobserver agreement, respectively. RESULTS: Among
      228 lesions, diameters of which ranges from 2 to 125 mm (mean, 13.84 +/- 16.24
      mm), 56.14% of them (n = 128) were hemangiomas, and 43.86% of them were cysts (n
      = 100). In the receiver operating characteristic analysis for the differentiation
      of hepatic hemangiomas from cysts, the calculated area under the curve (AUC) for
      standard T2W images alone was 0.889 (95% confidence interval [CI], 0.825-0.953)
      for the first observer and 0.913 (95% CI, 0.861-0.965) for the second observer.
      When IR-SSFSE sequence was combined to T2W images, AUC was calculated as 0.958
      (95% CI, 0.920-0.996) for the first observer and 0.980 (95% CI, 0.956-1.0) for
      the second observer. The AUC values obtained from standard T2W images and
      standard T2W plus IR-SSFSE images were significantly different for both observers
      (P < 0.01). Both observers demonstrate better performance in differentiating
      hemangiomas and cysts with a combination of IR-SSFSE sequence and T2W imaging
      than with T2W imaging alone. Adding IR-SSFSE sequence as a supplement to standard
      T2W images improved the sensitivity and the kappa values. CONCLUSIONS: Inversion
      recovery single-shot fast-spin echo sequence using the inversion time to null
      signal from the hepatic hemangiomas as a supplement to standard T2W images is
      useful for distinguishing hemangiomas from hepatic cysts without the need for
      intravenous gadolinium chelate administration.

PMID- 25955399
TI  - Masquerading Orbital Abscess Following Attempted Hydrogel Scleral Buckle Removal:
      Diagnostic Value of Orbital Magnetic Resonance Spectroscopy.
AB  - A 59-year-old patient developed acute proptosis, peri-orbital swelling and
      restriction of ocular movements 2 days after attempted scleral buckle removal.
      Initial clinical and orbital MRI findings were suggestive for orbital cellulitis
      and orbital abscess. Empiric intravenous antibiotics were not effective. Proton
      magnetic resonance spectroscopy (MRS) revealed a distinctive composition and
      helped rule out suppurative and neoplastic processes. The patient recovered soon
      after removing clear liquefied and tiny particles of the hydrogel buckle by an
      effective peristaltic technique. 

PMID- 25955400
TI  - Relative biological effectiveness of radon: An in vitro study using chromosome
      aberrations as a biomarker.
AB  - PURPOSE: The need to determine a reliable relative biological effectiveness (RBE)
      value for alpha exposures has become important as reports remain controversial.
      Although a radiation-weighting factor of 20 has been designated for alpha
      particles, uncertainty exists on realistic value of the RBE of alpha radiation.
      The aim of this study was to estimate RBE values for radon using chromosome
      aberrations as the endpoint in respect to various dose rates of gamma radiation.
      MATERIALS AND METHODS: Human blood samples were exposed ex vivo to different
      doses of radon ranging from 0.0011-0.008 Gy. Blood samples were also exposed to
      gamma radiation with dose rates of 1, 0.1, 0.01 and 0.001 Gy/min. Chromosome
      aberrations in giemsa-stained first division metaphase preparations were scored.
      RESULTS: Dose response curves for dicentric chromosomal aberration yields were
      generated for both radon and gamma rays. Radon dose rates were compared with
      gamma dose rates to deduce RBE values. The values obtained were 16, 25, 29 and 38
      for reference gamma dose-rates of 1, 0.1, 0.01 and 0.001 Gy/min, respectively.
      CONCLUSIONS: The study indicates that an RBE value of radon can range between 16
      and 38, if one were to consider chromosome aberrations as an effective biomarker
      of risk due to ionizing radiation.

PMID- 25955401
TI  - Postsynthetic Modification of an Alkyne-Tagged Zirconium Metal-Organic Framework
      via a "Click" Reaction.
AB  - Herein, we report the synthesis and postsynthetic modification of a novel alkyne
      tagged zirconium metal-organic framework, UiO-68-alkyne. The alkynyl groups in
      the pore surface were subjected to a "click" reaction, achieving quantitative
      conversion and maintaining the crystallinity of the framework. 

PMID- 25955402
TI  - Curcumin-cysteine and curcumin-tryptophan conjugate as fluorescence turn on
      sensors for picric Acid in aqueous media.
AB  - Rapid detection of picric acid in real sample is of outmost importance from the
      perspective of health, safety, and environment. In this study, a very simple and
      cost-effective detection of picric acid is accomplished by developing a couple of
      biobased conjugates curcumin-cysteine (CC) and curcumin-tryptophan (CT), which
      undergo efficient fluorescence turn on toward picric acid in aqueous media. Both
      the probes experience about 26.5-fold fluorescence enhancements at 70 nM
      concentration of the analyte. Here, the fluorescence turn on process is governed
      by the aggregation induced emission, which is induced from the electrostatic
      interaction between the conjugates with picric acid. The detection limit of CC
      and CT are about 13.51 and 13.54 nM of picric acid, respectively. Importantly,
      both the probes exhibit high selectivity and low interference of other analogues
      toward the detection of picric acid. In addition, the probes are highly
      photostable, show low response time and are practically applicable for sensing
      picric acid in real environmental samples, which is the ultimate goal of this
      work. 

PMID- 25955403
TI  - Surrogate testing suggests that chlorine dioxide gas exposure would not
      inactivate Ebola virus contained in environmental blood contamination.
AB  - The ability to decontaminate a room potentially containing the Ebola virus is
      important to healthcare facilities in the United States. Ebola virus remains
      viable in body fluids, a room that has housed a patient with Ebola virus disease
      must have all surfaces manually wiped with an approved disinfectant, which
      increases occupational exposure risk. This study evaluated the efficacy of
      gaseous chlorine dioxide inactivation of bacterial organisms in blood as Ebola
      virus surrogates and as the organisms used by the Nebraska Biocontainment Unit to
      provide the margin of safety for decontamination. Bacillus anthracis, Escherichia
      coli, Enterococcus faecalis, and Mycobacterium smegmatis blood suspensions that
      were exposed to ClO2 gas concentrations and exposure limits. The log reduction in
      Colony Forming Units (CFU) was determined for each bacterial blood suspension.
      Exposure parameters approximating industry practices for ClO2 environmental
      decontamination (360ppm concentration to 780 ppm-hrs exposure, 65% relative
      humidity) as well as parameters exceeding current practice (1116 ppm
      concentration to 1400 ppm-hrs exposure; 1342ppm concentration to 1487 ppm-hrs
      exposure) were evaluated. Complete inactivation was not achieved for any of the
      bacterial blood suspensions tested. Reductions were observed in concentrations of
      B. anthracis spores (1.3 -3.76 log) and E. faecalis vegetative cells (1.3 log)
      whereas significant reductions in vegetative cell concentrations for E. coli and
      M. smegmatis blood suspensions were not achieved. Our results showed that
      bacteria in the presence of blood were not inactivated using gaseous ClO2
      decontamination. ClO2 decontamination alone should not be used for Ebola virus,
      but decontamination processes should first include manual wiping of potentially
      contaminated blood; especially for microorganisms as infectious as the Ebola
      virus.

PMID- 25955404
TI  - Heat tolerance after total and partial acute sleep deprivation.
AB  - Sleep deprivation (SD) is suggested to be associated with reduced thermo
      regulatory functions. This study aimed to quantify the effect of partial (PSD)
      and total (TSD) 24 h SD using a standard heat tolerance test (HTT). Eleven
      participants underwent HTT after well-rested state, PSD and TSD. No significant
      physiological differences were found between the exposures but subjective
      discomfort was higher after TSD. Evening chronotypes' temperature during HTT was
      higher after TSD compared with PSD (p = 0.017). After TSD, evening chronotypes
      compared to intermediate chronotypes' temperature was higher during the first
      hour of the HTT (p < 0.05), suggesting that thermo-regulatory function during
      exercise in the heat is influenced by chronotype. 

PMID- 25955405
TI  - High prevalence of breast cancer in light polluted areas in urban and rural
      regions of South Korea: An ecologic study on the treatment prevalence of female
      cancers based on National Health Insurance data.
AB  - It has been reported that excessive artificial light at night (ALAN) could harm
      human health since it disturbs the natural bio-rhythm and sleep. Such conditions
      can lead to various diseases, including cancer. In this study, we have evaluated
      the association between ALAN and prevalence rates of cancer in females on a
      regional basis, after adjusting for other risk factors, including obesity,
      smoking, alcohol consumption rates and PM10 levels. The prevalence rates for
      breast cancer were found to be significantly associated with ALAN in urban and
      rural areas. Furthermore, no association was found with ALAN in female lung,
      liver, cervical, gastric and colon cancer. Despite the limitations of performing
      ecological studies, this report suggests that ALAN might be a risk factor for
      breast cancer, even in rural areas. 

PMID- 25955406
TI  - Effect of BML-111 on the intestinal mucosal barrier in sepsis and its mechanism
      of action.
AB  - 5(S),6(R)-7-trihydroxymethyl heptanoate (BML-111) is an lipoxin A4 receptor
      agonist, which modulates the immune response and attenuates hemorrhagic shock
      induced acute lung injury. However, the role of BML-111 in sepsis and in the
      intestinal mucosal barrier are not well understood. Therefore, the present study
      was designed to investigate the effect of BML-111 on the intestinal mucosal
      barrier in a rat model of sepsis. Furthermore, the molecular mechanism of action
      of BML-111 was evaluated. The cecal ligation and puncture-induced rat model of
      sepsis was constructed, and BML-111 was administered at three different doses.
      The results revealed that BML-111 suppressed the elevation of the pro
      inflammatory cytokines tumor necrosis factor-alpha and interleukin-6, while
      enhancing the elevation of the anti-inflammatory cytokine transforming growth
      factor-beta in the intestine. In addition, BML-111 significantly upregulated rat
      defensin-5 mRNA expression levels and downregulated the induction of cell
      apoptosis as well as caspase-3 activity in the intestine. All these results
      demonstrated that BML-111 exerted protective effects on the intestinal mucosal
      barrier in sepsis. Further, it was indicated that alterations in the expression
      of toll-like receptor (TLR)2 and TLR4 may be one of the molecular mechanisms
      underlying the protective effect of BML-111. The present study therefore
      suggested that BML-111 may be a novel therapeutic agent for sepsis.

PMID- 25955407
TI  - Role of Exchange Protein Activated by cAMP 1 in Regulating Rates of Microtubule
      Formation in Cystic Fibrosis Epithelial Cells.
AB  - The regulation of microtubule dynamics in cystic fibrosis (CF) epithelial cells
      and the consequences of reduced rates of microtubule polymerization on downstream
      CF cellular events, such as cholesterol accumulation, a marker of impaired
      intracellular transport, are explored here. It is identified that microtubules in
      both CF cell models and in primary CF nasal epithelial cells repolymerize at a
      slower rate compared with respective controls. Previous studies suggest a role
      for cAMP in modulating organelle transport in CF cells, implicating a role for
      exchange protein activated by cAMP (EPAC) 1, a regulator of microtubule
      elongation, as a potential mechanism. EPAC1 activity is reduced in CF cell models
      and in Cftr(-/-) mouse lung compared with respective non-CF controls. Stimulation
      of EPAC1 activity with the selective EPAC1 agonist, 8-cpt-2-O-Me-cAMP, stimulates
      microtubule repolymerization to wild-type rates in CF cells. EPAC1 activation
      also alleviates cholesterol accumulation in CF cells, suggesting a direct link
      between microtubule regulation and intracellular transport. To verify the
      relationship between transport and microtubule regulation, expression of the
      protein, tubulin polymerization-promoting protein, was knocked down in non-CF
      human tracheal (9/HTEo(-)) cells to mimic the microtubule dysregulation in CF
      cells. Transduced cells with short hairpin RNA targeting tubulin polymerization
      promoting protein exhibit CF-like perinuclear cholesterol accumulation and other
      cellular manifestations of CF cells, thus supporting a role for microtubule
      regulation as a mechanism linking CFTR function to downstream cellular
      manifestation. 

PMID- 25955408
TI  - Expression of beclin-1 in the microenvironment of invasive ductal carcinoma of
      the breast: correlation with prognosis and the cancer-stromal interaction.
AB  - We examined the pathobiological properties of beclin-1, which is a key regulator
      of autophagosome formation in invasive ductal carcinoma of the breast, with a
      particular focus on the cancer microenvironment. Immunohistochemistry
      demonstrated that cancer cells and stromal mesenchymal cells expressed beclin-1
      in 68 and 38 of 115 invasive ductal cancers, respectively. Expression of beclin-1
      in cancer or stromal cells alone did not correlate with patient prognosis. In
      contrast, loss of beclin-1 in cancer cells and overexpression in stromal
      mesenchymal cells was associated with local cancer recurrence, postoperative
      lymph node metastasis, and a poor disease-free survival rate. A comprehensive
      gene expression analysis was performed on a co-culture of breast cancer cells and
      mesenchymal stromal cells, that latter of which either expressed beclin-1 or was
      depleted of beclin-1 by siRNA. Notably, siRNA-mediated downregulation of beclin-1
      in mesenchymal cells co-cultured with breast cancer cells decreased the levels of
      various pro-inflammatory cytokines, their receptors, and collagen receptors.
      Quantitative reverse transcription polymerase chain reaction analysis confirmed
      that reduction of stromal beclin-1 expression decreased the expression of IL
      1beta and collagen receptor discoidin domain receptor 2 (DDR2).
      Microenvironmental IL-1beta is believed to play an important role in tumor
      invasion. Recent work has also indicated that overexpression of DDR2 contributes
      to breast cancer invasion and lymph node metastasis. Taken together, these
      findings indicate beclin-1 expression in the stroma might be important for
      shaping the breast cancer microenvironment and thus could be a potent molecular
      target in patients with invasive ductal carcinoma of the breast. 

PMID- 25955409
TI  - Interprofessional education: Lessons learned from conducting an electronic health
      record assignment.
AB  - Ineffective collaboration and communication contribute to fragmented patient care
      and potentially increase adverse events, clinical errors, and poor patient
      outcomes. Improving collaboration and communication is essential; however,
      interprofessional education (IPE) supporting this cause is not a common practice.
      Most often healthcare profession students are educated in profession-centered
      silos limiting opportunities to develop effective communication and collaboration
      practices. Students from nursing, health informatics, and radiologic technology
      collaboratively populated an academic electronic health record (AEHR) using
      fictitious case study data. The assignment was designed to address the Quality
      and Safety Education for Nurses and IPE Collaborative competencies. The objective
      was to evaluate students' informatics competency, teamwork behaviors, and
      communication skills while exploring the different roles and responsibilities for
      collaborative practice after participating in an interprofessional case study
      assignment. Students gained experience using the AEHR for data entry, analysis,
      and application increasing their informatics competency. The assignment required
      students to communicate and actively collaborate as an interprofessional team to
      achieve the assignment objectives. Clinical errors often occur during care
      transitions, so simulating this process in the assignment was essential. Nursing
      and radiologic technology students had to analyze patient data and develop a hand
      off communication template supporting patient safety and optimizing outcomes. The
      assignment required students to work as an interprofessional team and demonstrate
      how communication and collaboration is an essential component to quality and safe
      patient care. 

PMID- 25955411
TI  - The chemical biology of sirtuins.
AB  - The sirtuin family of enzymes are able to catalyze the N(epsilon)-acyl-lysine
      deacylation reaction on histone and non-histone protein substrates. Over the past
      years since the discovery of its founding member (i.e. the yeast silent
      information regulator 2 (sir2) protein) in 2000, the sirtuin-catalyzed
      deacylation reaction has been demonstrated to play an important regulatory role
      in multiple crucial cellular processes such as transcription, DNA damage repair,
      and metabolism. This reaction has also been regarded as a current therapeutic
      target for human diseases such as cancer, and metabolic and neurodegenerative
      diseases. The unique beta-nicotinamide adenine dinucleotide (beta-NAD(+) or
      NAD(+))-dependent nature of the sirtuin-catalyzed deacylation reaction has also
      engendered extensive mechanistic studies, resulting in a mechanistic view of the
      enzyme chemistry supported by several lines of experimental evidence. On the
      journey toward these knowledge advances, chemical biological means have
      constituted an important functional arsenal; technically, a variety of chemical
      probes and modulators (inhibitors and activators) have been developed and some of
      them have been employed toward an enhanced mechanistic and functional
      (pharmacological) understanding of the sirtuin-catalyzed deacylation reaction. On
      the other hand, an enhanced mechanistic understanding has also facilitated the
      development of a variety of chemical probes and modulators. This article will
      review the tremendous accomplishments achieved during the past few years in the
      field of sirtuin chemical biology. It is hoped that this would also help to set a
      stage for how outstanding mechanistic and functional questions for the sirtuin
      catalyzed deacylation reaction could be addressed in the future from the chemical
      biology perspective.

PMID- 25955412
TI  - Effect of the solvent on the size of clay nanoparticles in solution as determined
      using an ultraviolet-visible (UV-Vis) spectroscopy methodology.
AB  - Ultraviolet-visible (UV-Vis) spectroscopy methodology was developed and utilized
      for the in situ nanoscale measurement of the size of mineral clay agglomerates in
      various liquid suspensions. The clays studied were organomodified and unmodified
      montmorillonite clays (I.44p, Cloisite 93a, and PGN). The methodology was
      compared and validated against dynamic light scattering (DLS) analysis. The
      method was able to measure clay agglomerates in solvents in situations where DLS
      analysis was unsuccessful due to the shapes, polydispersity, and high aspect
      ratios of the clay particles and the complexity of the aggregates, or dispersion
      medium. The measured clay agglomerates in suspension were found to be in the
      nanometer range in the more compatible solvents, and their sizes correlated with
      the Hansen solubility parameter space distance between the clay modifiers and the
      solvents. Mass detection limits for size determination were in the range from 1
      to 9 mg/L. The methodology thus provides simple, rapid, and inexpensive
      characterization of clays or particles in the nano- or microsize range in low
      concentrations in various liquid media, including complex mixtures or highly
      viscous fluids that are difficult to analyze with DLS. In addition, by combining
      UV-VIS spectroscopy with DLS it was possible to discern flocculation behavior in
      liquids, which otherwise could result in false size measurements by DLS alone. 

PMID- 25955410
TI  - ACTH (Acthar Gel) Reduces Toxic SOD1 Protein Linked to Amyotrophic Lateral
      Sclerosis in Transgenic Mice: A Novel Observation.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a complex
      etiology and pathology that makes the development of new therapies difficult.
      ACTH has neurotrophic and myotrophic effects, but has not been tested in an ALS
      mouse model. The G93A-SOD1 mouse model of ALS was used to test the ability of
      this drug to delay ALS-like symptoms. We showed that within a specific dose
      range, ACTH significantly postponed the disease onset and paralysis in the mouse
      model. To our surprise and of greater significance is that ACTH significantly
      reduced the levels of soluble SOD1 in the spinal cord and CNS tissues of G93A
      SOD1 treated mice as well as cultured fibroblasts. 

PMID- 25955413
TI  - Iron-Catalyzed Enantioselective Cross-Coupling Reactions of alpha-Chloroesters
      with Aryl Grignard Reagents.
AB  - The first iron-catalyzed enantioselective cross-coupling reaction between an
      organometallic compound and an organic electrophile is reported. Synthetically
      versatile racemic alpha-chloro- and alpha-bromoalkanoates were coupled with aryl
      Grignard reagents in the presence of catalytic amounts of an iron salt and a
      chiral bisphosphine ligand, giving the products in high yields with acceptable
      and synthetically useful enantioselectivities (er up to 91:9). The produced alpha
      arylalkanoates were readily converted to the corresponding alpha-arylalkanoic
      acids with high optical enrichment (er up to >99:1) via simple
      deprotections/recrystallizations. The results of radical probe experiments are
      consistent with a mechanism that involves the formation of an alkyl radical
      intermediate, which undergoes subsequent enantioconvergent arylation in an
      intermolecular manner. The developed asymmetric coupling offers not only facile
      and practical access to various chiral alpha-arylalkanoic acid derivatives, which
      are of significant pharmaceutical importance, but also a basis of controlling
      enantioselectivity in an iron-catalyzed organometallic transformation. 

PMID- 25955415
TI  - Directed Differentiation of Oligodendrocyte Progenitor Cells From Mouse Induced
      Pluripotent Stem Cells.
AB  - Several neurological disorders, such as multiple sclerosis, the leukodystrophies,
      and traumatic injury, result in loss of myelin in the central nervous system
      (CNS). These disorders may benefit from cell-based therapies that prevent further
      demyelination or are able to restore lost myelin. One potential therapeutic
      strategy for these disorders is the manufacture of oligodendrocyte progenitor
      cells (OPCs) by the directed differentiation of pluripotent stem cells, including
      induced pluripotent stem cells (iPSCs). It has been proposed that OPCs could be
      transplanted into demyelinated or dysmyelinated regions of the CNS, where they
      would migrate to the area of injury before terminally differentiating into
      myelinating oligodendrocytes. OPCs derived from mouse iPSCs are particularly
      useful for modeling this therapeutic approach and for studying the biology of
      oligodendrocyte progenitors because of the availability of mouse models of
      neurological disorders associated with myelin deficiency. Moreover, the utility
      of miPSC-derived OPCs would be significantly enhanced by the adoption of a
      consistent, reproducible differentiation protocol that allows OPCs derived from
      different cell lines to be robustly characterized and compared. Here we describe
      a standardized, defined protocol that reliably directs the differentiation of
      miPSCs to generate high yields of OPCs that are capable of maturing into
      oligodendrocytes. 

PMID- 25955414
TI  - Morphological and Molecular Descriptors of the Developmental Cycle of Babesia
      divergens Parasites in Human Erythrocytes.
AB  - Human babesiosis, especially caused by the cattle derived Babesia divergens
      parasite, is on the increase, resulting in renewed attentiveness to this
      potentially life threatening emerging zoonotic disease. The molecular mechanisms
      underlying the pathophysiology and intra-erythrocytic development of these
      parasites are poorly understood. This impedes concerted efforts aimed at the
      discovery of novel anti-babesiacidal agents. By applying sensitive cell
      biological and molecular functional genomics tools, we describe the intra
      erythrocytic development cycle of B. divergens parasites from immature, mono
      nucleated ring forms to bi-nucleated paired piriforms and ultimately multi
      nucleated tetrads that characterizes zoonotic Babesia spp. This is further
      correlated for the first time to nuclear content increases during intra
      erythrocytic development progression, providing insight into the part of the life
      cycle that occurs during human infection. High-content temporal evaluation
      elucidated the contribution of the different stages to life cycle progression.
      Moreover, molecular descriptors indicate that B. divergens parasites employ
      physiological adaptation to in vitro cultivation. Additionally, differential
      expression is observed as the parasite equilibrates its developmental stages
      during its life cycle. Together, this information provides the first temporal
      evaluation of the functional transcriptome of B. divergens parasites, information
      that could be useful in identifying biological processes essential to parasite
      survival for future anti-babesiacidal discoveries. 

PMID- 25955416
TI  - Spatio-temporal dynamics of impulse responses to figure motion in optic flow
      neurons.
AB  - White noise techniques have been used widely to investigate sensory systems in
      both vertebrates and invertebrates. White noise stimuli are powerful in their
      ability to rapidly generate data that help the experimenter decipher the spatio
      temporal dynamics of neural and behavioral responses. One type of white noise
      stimuli, maximal length shift register sequences (m-sequences), have recently
      become particularly popular for extracting response kernels in insect motion
      vision. We here use such m-sequences to extract the impulse responses to figure
      motion in hoverfly lobula plate tangential cells (LPTCs). Figure motion is
      behaviorally important and many visually guided animals orient towards salient
      features in the surround. We show that LPTCs respond robustly to figure motion in
      the receptive field. The impulse response is scaled down in amplitude when the
      figure size is reduced, but its time course remains unaltered. However, a low
      contrast stimulus generates a slower response with a significantly longer time-to
      peak and half-width. Impulse responses in females have a slower time-to-peak than
      males, but are otherwise similar. Finally we show that the shapes of the impulse
      response to a figure and a widefield stimulus are very similar, suggesting that
      the figure response could be coded by the same input as the widefield response. 

PMID- 25955418
TI  - The importance of learning.

PMID- 25955417
TI  - The in-vivo use of superparamagnetic iron oxide nanoparticles to detect
      inflammation elicits a cytokine response but does not aggravate experimental
      arthritis.
AB  - BACKGROUND: Superparamagnetic Iron Oxide Nanoparticles (SPION) are used in
      diagnostic imaging of a variety of different diseases. For such in-vivo
      application, an additional coating with a polymer, for example polyvinyl alcohol
      (PVA), is needed to stabilize the SPION and prevent aggregation. As the particles
      are foreign to the body, reaction against the SPION could occur. In this study we
      investigated the effects that SPION may have on experimental arthritis after
      intra-articular (i.a.) or intravenous (i.v.) injection. METHODS: PVA-coated SPION
      were injected either i.a. (6 or 24 MUg iron) or i.v. (100 MUg or 1 mg iron) into
      naive Toll-like receptor-4 deficient (TLR4-/-) or wild-type C57Bl/6 mice, or
      C57Bl/6 mice with antigen-induced arthritis. As control, some mice were injected
      with PVA or PBS. MR imaging was performed at 1 and 7 days after injection. Mice
      were sacrificed 2 hours and 1, 2, 7, 10 and 14 days after injection of the SPION,
      and RNA from synovium and liver was isolated for pro-inflammatory gene expression
      analysis. Serum cytokine measurements and whole knee joint histology were also
      performed. RESULTS: Injection of a high dose of SPION or PVA into naive knee
      joints resulted in an immediate upregulation of pro-inflammatory gene expression
      in the synovium. A similar gene expression profile was observed after SPION or
      PVA injection into knee joints of TLR4-/- mice, indicating that this effect is
      not due to LPS contamination. Histological analysis of the knee joints also
      revealed synovial inflammation after SPION injection. Two hours after i.v.
      injection of SPION or PVA into naive mice, an upregulation of pro-inflammatory
      gene expression was detected in the liver. Administration of SPION or PVA into
      arthritic mice via i.a. injection did not result in an upregulation in gene
      expression and also no additional effects were observed on histology. MR imaging
      and histology showed long-term retention of SPION in the inflamed joint. However,
      14 days after the injections no long-term effects were evident for gene
      expression, histology or serum cytokine concentrations. CONCLUSIONS: Injection of
      SPION, either locally or systemically, gives an acute inflammatory response. In
      the long term, up to 14 days after the injection, while the SPION reside in the
      joint, no further activating effects of SPION were observed. Hence, we conclude
      that SPION do not aggravate arthritis and can therefore be used safely to detect
      joint inflammation by MR imaging.

PMID- 25955419
TI  - Developing a learner-directed, learner-paced activity.
AB  - The American Nurses Credentialing Center Primary Accreditation Program manual has
      for many years included the concept of learner-directed, learner-paced
      activities. However, due to many logistical challenges, this type of activity has
      not been implemented. In 2014, one organization successfully piloted the process.
      The methodology for developing this type of activity is explained in this
      article.

PMID- 25955420
TI  - Screening for distress in patients with cancer.
AB  - Distress screening, using the Distress Thermometer for Patients, is a valid,
      evidence-based approach to assess and facilitate the identification of
      interventions for patients and families experiencing cancer-related distress.
      Nurses are in position to lead early implementation of screenings and identify
      interventions for illness-related distress.

PMID- 25955421
TI  - Leadership and brilliant mistakes.
AB  - Professional development educators work fervently to model best practices and
      appropriate ways of being successful within health care organizations. However,
      mistakes are made and happen at every level and are part of organizational life.
      Innovation requires risk, and risk means that mistakes will happen. The anatomy
      of the mistake is presented and, when appropriate, celebrated.

PMID- 25955422
TI  - A game-based strategy for the staff development of home health care nurses.
AB  - This article describes gaming, an interactive teaching strategy that promotes
      active learning. An evaluation study conducted with home health care nurses
      tested the use of a game as a teaching tool. The study evaluated learning
      outcomes and learners' level of engagement and satisfaction with an educational
      game as a teaching method.

PMID- 25955423
TI  - Intercultural-global competencies for the 21st century and beyond.
AB  - Increased diversity exists in Anglo-Saxon countries, such as Australia, the
      United Kingdom, and the United States. By 2050, no single ethnic group is
      expected to be in a majority in the United States. Health care reform points to
      an urgent need for health care professionals, such as nursing, medicine, allied
      health, nutrition, and other interdisciplinary health care team members, to serve
      a multi-ethnic population by developing intercultural-global and 21st-century
      competencies. Nurse educators must acknowledge the need to familiarize themselves
      and integrate these competencies into university and continuing education
      programs by evaluating and reporting outcomes. All nurses can be expected to have
      these competencies as global citizens through local, intercultural, and global
      interactions and exchanges.

PMID- 25955425
TI  - Investigating internationally educated Taiwanese nurses' training and
      communication experiences in the United States.
AB  - BACKGROUND: The study objective was to construct an understanding of how
      educational training affected the cross-cultural communication experiences of
      five internationally educated Taiwanese nurses in the United States. METHOD: Data
      collection included focus group interviews, individual interviews, and background
      information surveys. A combination of narrative and thematic analysis was used to
      analyze data. RESULTS: Findings showed that the five participants believed their
      education and training did not prepare them well in U.S. health care
      communication. The training content lacked essential language needs and cultural
      knowledge of patient backgrounds, hospital subcultures, hospital policies, and
      nursing routines. In addition, clinical shadowing was limited in improving
      international nurses' English communication ability and building cultural
      competence. CONCLUSION: Internationally educated nurses require specialized
      language and nursing assessment and comprehensive on-the-job training to work in
      U.S. clinical settings. This study benefited the VisaScreen and U.S. hospitals
      toward filling the training gaps of language and culture for international
      nurses. It also contributed to the understanding of both Teaching English for
      Speakers of Other Language researchers and nurse educators about the complexity
      of cross-cultural clinical communication.

PMID- 25955426
TI  - Recognizing the dialectic of compassionate care in the workplace: feedback from
      nurse educators.
AB  - Compassionate care and compassion fatigue affects managers, clinicians, and
      patients and is gaining international recognition. Using the cafe methodology as
      a structure and nurse educators as participants, a compassion dialectic between
      the psychological intent of the nurse to be compassionate and a system designed
      on maximizing throughput, with the least inputs possible is identified. Our
      findings indicate that the cafe in itself is not sufficient to enable experienced
      educators to take responsibility for compassionate care, but the cafe methodology
      opens the space for the important steps of naming the problem, recognizing its
      dialectical nature, deflecting blame for compassion fatigue away from
      individuals, and balancing the responsibility for compassion across the spectrum
      of elements that enable care to take place.

PMID- 25955427
TI  - Preceptor skills and characteristics: considerations for preceptor education.
AB  - The onboarding and retention of new graduate RNs continues to be a critical focus
      for both nursing as a profession and for health care organizations. A
      comprehensive residency program, with preceptor engagement playing a key role, is
      essential to the success of these new nurses in transition. With a focus on
      preceptor education, this article provides an analysis of the preceptor
      experience from the perspective of new graduate RNs and how their feedback
      provided the foundation for preceptor education. The article outlines opinions
      and recommendations for preceptor development, provided by a convenience sample
      of new graduate nurses from a multisite, postresidency evaluation survey. The
      purpose of the analysis was two-fold: (a) to identify preceptor skills and
      characteristics for presentation at the 2nd annual American Academy for Preceptor
      Advancement conference and (b) to ensure that the identified skills and
      characteristics provide the foundation for preceptor education in a national
      residency program.

PMID- 25955428
TI  - A mathematical model to elucidate brain tumor abrogation by immunotherapy with
      T11 target structure.
AB  - T11 Target structure (T11TS), a membrane glycoprotein isolated from sheep
      erythrocytes, reverses the immune suppressed state of brain tumor induced animals
      by boosting the functional status of the immune cells. This study aims at aiding
      in the design of more efficacious brain tumor therapies with T11 target
      structure. We propose a mathematical model for brain tumor (glioma) and the
      immune system interactions, which aims in designing efficacious brain tumor
      therapy. The model encompasses considerations of the interactive dynamics of
      glioma cells, macrophages, cytotoxic T-lymphocytes (CD8(+) T-cells), TGF-beta,
      IFN-gamma and the T11TS. The system undergoes sensitivity analysis, that
      determines which state variables are sensitive to the given parameters and the
      parameters are estimated from the published data. Computer simulations were used
      for model verification and validation, which highlight the importance of T11
      target structure in brain tumor therapy.

PMID- 25955430
TI  - The first center for evidence-based medicine in Lithuania: an opportunity to
      change culture and improve clinical practice.
AB  - In post-Soviet countries, where medical practice largely relies on experience
      alone, the incorporation of the best research evidence in clinical practice is
      limited. In order to promote the awareness and utilization of evidence-based
      medicine (EBM) among Lithuanian doctors, we organized EBM conferences in each of
      the two Lithuanian medical schools. More than 500 medical professionals and
      students attended the conferences in Vilnius (2013) and Kaunas (2014)
      demonstrating that there is a high demand for formal EBM teaching. Building on
      the success of these seminal conferences, and to start addressing the lack of EBM
      practice in the country, the first Lithuanian Centre for Evidence-Based Medicine
      was established at Vilnius University Medical Faculty in 2014. The Centre will
      focus on the implementation of EBM teaching in medical school curriculum,
      formulating management guidelines, writing systematic reviews and supporting
      Lithuanian authors in doing so. 

PMID- 25955429
TI  - Interleukin-17A contributes to the development of post-operative atrial
      fibrillation by regulating inflammation and fibrosis in rats with sterile
      pericarditis.
AB  - Post-operative atrial fibrillation (AF) remains a common cause of morbidity.
      Increasing evidence indicates that inflammation and atrial fibrosis contribute to
      the pathogenesis of this condition. Interleukin (IL)-17A, a potent pro
      inflammatory cytokine, has been implicated in the development of a number of
      cardiovascular diseases. However, its role in post-operative AF remains unknown.
      In the present study, sterile pericarditis (SP) was induced in rats by the
      epicardial application of sterile talc. AF was induced by transesophageal burst
      pacing. Western blot analysis was applied to quantify the expression of IL-17A.
      Quantitative PCR was used to detect the mRNA expression of IL-17A, IL-6, IL
      1beta, transforming growth factor-beta1 (TGF-beta1), collagen type 1 (Col-1),
      collagen type 3 (Col-3) and alpha-smooth muscle actin (alpha-SMA). Gelatin
      zymography and reverse gelatin zymography were used to quantify the levels of
      matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs).
      Histological analyses were performed to determine the extent of tissue
      inflammation and fibrosis. The rats with SP presented with a shorter
      refractoriness, a higher incidence and duration of AF, an enhanced susceptibility
      to developing AF, increased mRNA levels of AF-related pro-inflammatory cytokines
      (IL-6, IL-1beta and TGF-beta1), as well as marked atrial inflammation and
      fibrosis. The atrial IL-17A levels were elevated and correlated with the
      probability of developing AF. Treatment with anti-IL-17A monoclonal antibody
      decreased the levels of atrial IL-17A, prolonged refraction and markedly
      suppressed the development of AF. Simultaneously, inflammation and fibrosis were
      alleviated, which was further demonstrated by a decreased expression of AF
      related pro-inflammatory cytokines, a downregulation in fibrosis-related mRNA
      expression (Col-1, Col-3 and alpha-SMA) and by the decreased activity of MMP-2/9
      and TIMPs. Thus, the findings of our study indicate that IL-17A may play a
      pathogenic role in post-operative AF by inducing inflammation and fibrosis in
      rats with SP.

PMID- 25955431
TI  - Type I, Type II, and Occasionally Type III: How Can We Go Wrong?
AB  - An important part of planning a study is deciding what risk of drawing incorrect
      conclusions is acceptable. Type I error occurs when a study draws a false
      positive conclusion. A false negative, not appreciating a difference when one
      exists, is known as type II error. This article reviews the difference between
      the 2 common types of error and discusses conventions used to set acceptable
      error levels. 

PMID- 25955432
TI  - Analysis of different fates of DNA adducts in adipocytes post-sulfur mustard
      exposure in vitro and in vivo using a simultaneous UPLC-MS/MS quantification
      method.
AB  - Sulfur mustard (SM) is a powerful alkylating vesicant that can rapidly penetrate
      skin, ocular, and lung bronchus mucous membranes and react with numerous
      nucleophiles in vivo. Although the lesion mechanisms of SM remain unclear, DNA
      damage is believed to be the most crucial factor in initiating SM-induced
      toxicity. Four major DNA adducts were identified for retrospective detection and
      DNA lesion evaluation, namely, N(7)-[2-[(2-hydroxyethyl)thio]-ethyl]guanine (N(7)
      HETEG), bis(2-ethyl-N(7)-guanine)thioether (Bis-G), N(3)-(2
      hydroxyethylthioethyl)-2'-adenine (N(3)-HETEA), and O(6)-[2-[(2
      hydroxyethyl)thio]-ethyl]guanine (O(6)-HETEG). Because of previous observations
      that the levels of SM-DNA adducts were relatively higher in adipose-rich organs,
      such as the brain, we focused on the in vitro and in vivo fates of the DNA
      adducts in exposed adipocytes. A UPLC-MS/MS method developed in our laboratory
      was used to profile the N(7)-HETEG, Bis-G, and N(3)-HETEA levels in human mature
      adipocytes (HA-s) that had differentiated from human subcutaneous preadipocytes
      (HPA-s). This method was also used to profile three other cell lines related to
      the targeting of major tissues, including human keratinocytes (HaCaT), human
      hepatocytes (L-02), and human lung fibroblasts (HLF). Long-lasting adduct
      persistence and a high proportion of Bis-G were found in exposed adipocytes in
      vitro. The survival properties of exposed adipocytes were also tested. At the
      same time, the fate of SM-DNA adducts in vivo was characterized using a rat model
      exposed to 1 and 10 mg/kg doses of SM. The level of DNA adducts in the exposed
      adipose tissue (AT) was much lower than those in other organs studied in our
      previous work. The adduct persistence behavior was observed in AT with an
      extremely high proportion of Bis-G, which was higher than N(7)-HETEG. In light of
      these results, we suggest that an adipose-rich environment may promote the
      formation of Bis-G and that adipocyte-specific DNA repair mechanisms may result
      in adduct persistence and the survival of adipocytes after SM exposure. These
      conclusions should be further investigated.

PMID- 25955434
TI  - Antitumor activity of YM155, a selective survivin suppressant, in combination
      with cisplatin in hepatoblastoma.
AB  - Cisplatin (CDDP) is a chemotherapeutic drug that is often used for the treatment
      of hepatoblastoma. However, many patients acquire resistance to therapeutic
      agents leading to local and distant treatment failure. It has been shown that
      suppression survivin contributed to the inhibition of tumor growth and enhanced
      chemotherapeutic sensitivity in several types of cancer. The aim of the present
      study was to determine whether treatment with sepantronium bromide (YM155), a
      novel small molecule inhibitor of survivin, enhanced the sensitivity of CDDP to
      hepatoblastoma cells, leading to the therapeutic efficacy of cisplatin. In vitro
      and in vivo models were used to examine the anticancer efficacy of YM155, either
      as a monotherapy or in combination with CDDP to identify more effective
      therapeutics against hepatoblastoma. The results showed that survivin expression
      was upregulated in hepatoblastoma tissues and cell lines, and that YM155
      inhibited survivin expression in hepatoblastoma cells in a dose-dependent manner.
      YM155 enhanced sensitivity of CDDP to human HepG2 and HuH-6 hepatoblastoma cells.
      The YM155 combination with CDDP in hepatoblastoma cells significantly decreased
      cell proliferation and formation, and induced cell apoptosis than either agent
      alone. In a mouse xenograft model, YM155 combined with CDDP significantly
      suppressed tumor growth compared to the monotherapy. Taken together, these
      findings suggested that the combination of YM155 and CDDP is a promising drug
      candidate for the treatment of hepatoblastoma.

PMID- 25955433
TI  - The effect of alcohol and hydrogen peroxide on liver hepcidin gene expression in
      mice lacking antioxidant enzymes, glutathione peroxidase-1 or catalase.
AB  - This study investigates the regulation of hepcidin, the key iron-regulatory
      molecule, by alcohol and hydrogen peroxide (H2O2) in glutathione peroxidase-1
      (gpx-1(-/-)) and catalase (catalase(-/-)) knockout mice. For alcohol studies, 10%
      ethanol was administered in the drinking water for 7 days. Gpx-1(-/-) displayed
      significantly higher hepatic H2O2 levels than catalase(-/-) compared to wild-type
      mice, as measured by 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA). The
      basal level of liver hepcidin expression was attenuated in gpx-1(-/-) mice.
      Alcohol increased H2O2 production in catalase(-/-) and wild-type, but not gpx-1(
      /-), mice. Hepcidin expression was inhibited in alcohol-fed catalase(-/-) and
      wild-type mice. In contrast, alcohol elevated hepcidin expression in gpx-1(-/-)
      mice. Gpx-1(-/-) mice also displayed higher level of basal liver CHOP protein
      expression than catalase(-/-) mice. Alcohol induced CHOP and to a lesser extent
      GRP78/BiP expression, but not XBP1 splicing or binding of CREBH to hepcidin gene
      promoter, in gpx-1(-/-) mice. The up-regulation of hepatic ATF4 mRNA levels,
      which was observed in gpx-1(-/-) mice, was attenuated by alcohol. In conclusion,
      our findings strongly suggest that H2O2 inhibits hepcidin expression in vivo.
      Synergistic induction of CHOP by alcohol and H2O2, in the absence of gpx-1,
      stimulates liver hepcidin gene expression by ER stress independent of CREBH.

PMID- 25955436
TI  - Simulation of multi-frequency EPR spectra for a distribution of the zero-field
      splitting.
AB  - We present a numerical procedure called 'grid-of-errors' to extract the
      distribution of magnetic interactions from continuous-wave electron-paramagnetic
      resonance (EPR) spectra at multiple microwave frequencies. The approach is based
      on the analysis of the lineshape of the spectra and explicitly worked out for
      high-spin systems for which the lineshape is determined by a distribution of the
      zero-field splitting. Initial principal values of the zero-field splitting tensor
      are obtained from the EPR spectrum at a microwave frequency in the high-field
      limit, and the initial distribution is taken Gaussian. Subsequently, the grid-of
      errors procedure optimizes this distribution, without any restriction to its
      shape, taking into account spectra at various microwave frequencies. The
      numerical procedure is illustrated for the Fe(III)-EDTA complex. An optimized
      distribution of the zero-field splitting is obtained, which provides a proper
      description of the EPR spectra at 9.5, 34, 94, and 275 GHz. The proposed approach
      can be used as well for distributions of magnetic interactions other than the
      zero-field splitting.

PMID- 25955435
TI  - Brain-derived neurotrophic factor is a novel target gene of the has-miR
      183/96/182 cluster in retinal pigment epithelial cells following visible light
      exposure.
AB  - Light-induced retinal injury is clinically and experimentally well-documented. It
      may be categorized into three types: Photothermal, photomechanical and
      photochemical injuries. To date, the variation in the hsa-miR-183/96/182 cluster
      and its potential target genes in human primary retinal pigment epithelial (RPE)
      cells, following visible light exposure, has not been reported. In the present
      study, RPE cells were exposed to 4 h of constant visible light. The expression of
      the hsa-miR-183/96/182 cluster was determined using reverse transcription
      quantitative polymerase chain reaction (RT-qPCR) and its potential target genes
      were investigated. Additionally, hsa-miR-183, hsa-miR-96, hsa-miR-182 and has-miR
      183/96/182 mimics were designed and synthesized in vitro, and transfected into
      the RPE cells. Subsequently, the expression of brain-derived neurotrophic factor
      (BDNF) mRNA and protein was measured, using RT-qPCR and western blotting,
      respectively. The regulation of miRNAs to the BDNF gene were then validated using
      a dual luciferase reporter gene assay system. The expression of hsa-miR-183, hsa
      miR-96 and hsa-miR-182 significantly increased in RPE cells following 4 h of
      visible light exposure, compared with RPE cells that had been exposed to dark
      conditions (P<0.01). Following RPE cell transfection with mimics, BDNF mRNA and
      protein expression in the RPE cells was significantly downregulated compared with
      control RPE cells (P<0.05, P<0.01, respectively). Similarly, the ratio of Renilla
      luciferase/firefly luciferase significantly decreased in the RPE cells of the
      mimic + wild type (WT) group compared with cells of the psiCHECK(TM)-2 (a vector
      lacking the sequence of the BDNF gene), wild type and mimic + mutation groups
      (P<0.05, P<0.01). The present study suggests that BDNF is a target gene of the
      has-miR-183-96-182 cluster in RPE cells. The present study suggests an underlying
      protective mechanism against retinal light injury and may provide a novel target
      for the prevention and treatment of light-induced retinal injury.

PMID- 25955437
TI  - Dynamic nuclear polarization in the hyperfine-field-dominant region.
AB  - Dynamic nuclear polarization (DNP) allows measuring enhanced nuclear magnetic
      resonance (NMR) signals. Though the efficiency of DNP has been known to increase
      at low fields, the usefulness of DNP has not been throughly investigated yet.
      Here, using a superconducting quantum interference device-based NMR system, we
      performed a series of DNP experiments with a nitroxide radical and measured DNP
      spectra at several magnetic fields down to sub-microtesla. In the DNP spectra,
      the large overlap of two peaks having opposite signs results in net enhancement
      factors, which are significantly lower than theoretical expectations and nearly
      invariant with respect to magnetic fields below the Earth's field. The numerical
      analysis based on the radical's Hamiltonian provides qualitative explanations of
      such features. The net enhancement factor reached 325 at maximum experimentally,
      but our analysis reveals that the local enhancement factor at the center of the
      rf coil is 575, which is unaffected by detection schemes. We conclude that DNP in
      the hyperfine-field-dominant region yields sufficiently enhanced NMR signals at
      magnetic fields above 1 MUT.

PMID- 25955438
TI  - Numerical Simulation of Abandoned Gob Methane Drainage through Surface Vertical
      Wells.
AB  - The influence of the ventilation system on the abandoned gob weakens, so the gas
      seepage characteristics in the abandoned gob are significantly different from
      those in a normal mining gob. In connection with this, this study physically
      simulated the movement of overlying rock strata. A spatial distribution function
      for gob permeability was derived. A numerical model using FLUENT for abandoned
      gob methane drainage through surface wells was established, and the derived
      spatial distribution function for gob permeability was imported into the
      numerical model. The control range of surface wells, flow patterns and
      distribution rules for static pressure in the abandoned gob under different well
      locations were determined using the calculated results from the numerical model. 

PMID- 25955439
TI  - MOF-derived ultrafine MnO nanocrystals embedded in a porous carbon matrix as high
      performance anodes for lithium-ion batteries.
AB  - Although MnO has been demonstrated to be a promising anode material for lithium
      ion batteries (LIBs) in terms of its high theoretical capacity (755 mA h g(-1)),
      comparatively low voltage hysteresis (<0.8 V), low cost, and environmental
      benignity, the application of MnO as a practical electrode material is still
      hindered by many obstacles, including poor cycling stability and huge volume
      expansion during the charge/discharge process. Herein, we report a facile and
      scalable metal-organic framework-derived route for the in situ fabrication of
      ultrafine MnO nanocrystals encapsulated in a porous carbon matrix, where
      nanopores increase active sites to store redox ions and enhance ionic diffusivity
      to encapsulated MnO nanocrystals. As an anode material for lithium-ion batteries
      (LIBs), these MnO@C composites exhibited a high reversible specific capacity of
      1221 mA h g(-1) after 100 cycles at a current density of 100 mA g(-1). The
      excellent electrochemical performance can be attributed to their unique structure
      with MnO nanocrystals dispersed uniformly inside a porous carbon matrix, which
      can largely enhance the electrical conductivity and effectively avoid the
      aggregation of MnO nanocrystals, and relieve the strain caused by the volumetric
      change during the charge/discharge process. This facile and economical strategy
      will extend the scope of metal-organic framework-derived synthesis for other
      materials in energy storage applications. 

PMID- 25955440
TI  - The T cell receptor resides in ordered plasma membrane nanodomains that aggregate
      upon patching of the receptor.
AB  - Two related models for T cell signalling initiation suggest either that T cell
      receptor (TCR) engagement leads to its recruitment to ordered membrane domains,
      often referred to as lipid rafts, where signalling molecules are enriched or that
      ordered TCR-containing membrane nanodomains coalesce upon TCR engagement. That
      ordered domains form upon TCR engagement, as they do upon lipid raft marker
      patching, has not been considered. The target of this study was to differentiate
      between those three options. Plasma membrane order was followed in live T cells
      at 37  degrees C using laurdan to report on lipid packing. Patching of the TCR
      that elicits a signalling response resulted in aggregation, not formation, of
      ordered plasma membrane domains in both Jurkat and primary T cells. The TCR
      colocalised with actin filaments at the plasma membrane in unstimulated Jurkat T
      cells, consistent with it being localised to ordered membrane domains. The
      colocalisation was most prominent in cells in G1 phase when the cells are ready
      to commit to proliferation. At other cell cycle phases the TCR was mainly found
      at perinuclear membranes. Our study suggests that the TCR resides in ordered
      plasma membrane domains that are linked to actin filaments and aggregate upon TCR
      engagement. 

PMID- 25955441
TI  - Risk factors for acute asthma in tropical America: a case-control study in the
      City of Esmeraldas, Ecuador.
AB  - BACKGROUND: Despite the high asthma rates described in Latin America, asthma risk
      factors in poor urban settings are not well established. We investigated risk
      factors for acute asthma among Ecuadorian children. METHODS: A matched case
      control study was carried out in a public hospital serving a coastal city.
      Children with acute asthma were age- and sex-matched to non-asthmatics. A
      questionnaire was administered, and blood, as well as stool, and nasopharyngeal
      swabs were collected. RESULTS: Sixty cases and 119 controls aged 5-15 were
      evaluated. High proportions of cases were atopic with population-attributable
      fractions for atopy of 68.5% for sIgE and 57.2% for SPT. Acute asthma risk
      increased with greater titers of mite IgE (3.51-50 kU/l vs. <0.70kU/l - OR 4.56,
      95% CI 1.48-14.06, p = 0.008; >50kU/l vs. <0.70kU/l - OR 41.98, 95% CI: 8.97
      196.39, p < 0.001). Asthma risk was significantly independently associated with
      bronchiolitis (adj. OR: 38.9, 95% CI 3.26-465), parental educational level (adj.
      OR 1.26, 95% CI: 1.08-1.46), and presence of sIgE (adj. OR: 36.7, 95% CI: 4.00
      337), while a reduced risk was associated with current contact with pets (adj.
      OR: 0.07, 95% CI: 0.01-0.56). Rhinovirus infection was more frequent in cases
      (cases 35.6% vs. controls 7.8%, p = 0.002). None of the cases were on maintenance
      therapy with inhaled corticosteroids and most relied on emergency department for
      control. CONCLUSIONS: A high proportion of children presenting to a public
      hospital with acute asthma were allergic to mite, particularly at high IgE titer.
      Poor asthma control resulted in overuse of emergency care.

PMID- 25955442
TI  - Solexa-Sequencing Based Transcriptome Study of Plaice Skin Phenotype in Rex
      Rabbits (Oryctolagus cuniculus).
AB  - BACKGROUND: Fur is an important genetically-determined characteristic of domestic
      rabbits; rabbit furs are of great economic value. We used the Solexa sequencing
      technology to assess gene expression in skin tissues from full-sib Rex rabbits of
      different phenotypes in order to explore the molecular mechanisms associated with
      fur determination. METHODOLOGY/PRINCIPAL FINDINGS: Transcriptome analysis
      included de novo assembly, gene function identification, and gene function
      classification and enrichment. We obtained 74,032,912 and 71,126,891 short reads
      of 100 nt, which were assembled into 377,618 unique sequences by Trinity strategy
      (N50=680 nt). Based on BLAST results with known proteins, 50,228 sequences were
      identified at a cut-off E-value >= 10-5. Using Blast to Gene Ontology (GO),
      Clusters of Orthologous Groups (KOG) and Kyoto Encyclopedia of Genes and Genomes
      (KEGG), we obtained several genes with important protein functions. A total of
      308 differentially expressed genes were obtained by transcriptome analysis of
      plaice and un-plaice phenotype animals; 209 additional differentially expressed
      genes were not found in any database. These genes included 49 that were only
      expressed in plaice skin rabbits. The novel genes may play important roles during
      skin growth and development. In addition, 99 known differentially expressed genes
      were assigned to PI3K-Akt signaling, focal adhesion, and ECM-receptor interactin,
      among others. Growth factors play a role in skin growth and development by
      regulating these signaling pathways. We confirmed the altered expression levels
      of seven target genes by qRT-PCR. And chosen a key gene for SNP to found the
      differentially between plaice and un-plaice phenotypes rabbit.
      CONCLUSIONS/SIGNIFICANCE: The rabbit transcriptome profiling data provide new
      insights in understanding the molecular mechanisms underlying rabbit skin growth
      and development.

PMID- 25955443
TI  - Randomized controlled trial of web-based multimodal therapy for unilateral
      cerebral palsy to improve occupational performance.
AB  - AIM: The study aimed to investigate the effectiveness of a web-based therapy
      programme, 'Move it to improve it' (Mitii(TM)), in children with unilateral
      cerebral palsy (UCP) on occupational performance, upper limb function, and visual
      perception. METHOD: Participants (n=102) were matched in pairs and randomized to
      intervention (Mitii for 20wks; 26 males, mean age 11y 8mo [2y 4mo], Manual
      Ability Classification System level I=11, II=39, III=1) or control (standard
      care; 25 males, mean age 11y 10mo [2y 5mo], Manual Ability Classification System
      level I=13, II=37). Outcomes were the Assessment of Motor and Process Skills
      (AMPS), Assisting Hand Assessment, Jebsen-Taylor Test of Hand Function (JTTHF),
      Melbourne Assessment of Unilateral Upper Limb Function (MUUL), Canadian
      Occupational Performance Measure (COPM), and Test of Visual Perceptual Skills
      (TVPS-3). RESULTS: Participants completed on average 32.4 hours of Mitii (range
      3.7-74.7h). The Mitii group demonstrated significantly greater post-intervention
      scores than the comparison group on the AMPS, JTTHF dominant upper limb, COPM,
      and TVPS-3. The differences between groups were not clinically significant. There
      were no differences between groups on measures of impaired upper limb function.
      INTERPRETATION: Mitii delivers individualized, web-based therapy at home and has
      potential to increase therapy dose. Mitii can be considered as an option to
      enhance occupational performance and visual perception for children with UCP.

PMID- 25955445
TI  - The sacrificial role of graphene oxide in stabilising a Fenton-like catalyst GO
      Fe3O4.
AB  - Owing to the electron donor-acceptor properties of GO, the active sites ([triple
      bond, length as m-dash]Fe(2+)) of Fe3O4 are not oxidised ([triple bond, length as
      m-dash]Fe(3+)) in the heterogeneous Fenton-like reaction. GO plays a sacrificial
      role via the oxidation of (C[double bond, length as m-dash]C) carbon domains, and
      transferring electrons to Fe3O4. Therefore, GO-Fe3O4 confers superior catalytic
      efficiency, recyclability and longevity, otherwise not available in Fe3O4. 

PMID- 25955444
TI  - Risk factors for post-ERCP pancreatitis and hyperamylasemia: A retrospective
      single-center study.
AB  - OBJECTIVE: With an increased use of endoscopic retrograde
      cholangiopancreatography (ERCP), post-ERCP complications have attracted much
      attention. We aimed to identify independent risk factors of post-ERCP
      pancreatitis (PEP) and hyperamylasemia, and to develop a simple scoring system of
      the factors contributing to the clinical prevention against PEP. METHODS: A
      retrospective single-center analysis was performed in 4234 ERCP procedures
      between September 2007 and December 2012. Patient-related and procedure-related
      risk factors for PEP and post-ERCP hyperamylasemia were identified by univariate
      and multivariate regression analyses. A scoring system was developed based on the
      independent risk factors. RESULTS: PEP occurred in 226 (5.3%) ERCP procedures and
      hyperamylasemia in 774 (18.3%) procedures. Female gender (odds ratio [OR] 1.449),
      first-time ERCP (OR 1.745), latent jaundice (OR 1.917), difficult cannulation (OR
      3.317) and pancreatography (OR 1.823) were all proven to be significant risk
      factors for predicting PEP. In addition, difficult cannulation (OR 1.990) and
      pancreatography (OR 2.009), age <60 years (OR 1.294), prior diabetes (OR 0.614),
      biliary duct stent placement (OR 1.884) and nasobiliary drainage (OR 1.613) were
      associated with developing hyperamylasemia. Prophylactic pancreatic duct stent
      (PS) might prevent against PEP in significantly high-risk patients (score >=6).
      CONCLUSIONS: Both patient-related and procedure-related risk factors are
      important for predicting PEP and post-ERCP hyperamylasemia. Technical procedures,
      for example, PS, are necessary to prevent PEP in patients at the highest risk.

PMID- 25955446
TI  - The art and science of clinical medicine and editorial policy.

PMID- 25955447
TI  - To the editor: pheochromocytoma.

PMID- 25955448
TI  - In reply: pheochromocytoma.

PMID- 25955449
TI  - To the Editor: Pulmonary tuberculosis.

PMID- 25955450
TI  - In Reply: Pulmonary tuberculosis.

PMID- 25955451
TI  - Heart on the right may sometimes be 'right'.

PMID- 25955452
TI  - Eruptive xanthoma.

PMID- 25955453
TI  - A nonhealing oral ulcer in a man with HIV.

PMID- 25955454
TI  - Can the test for human papillomavirus DNA be used as the stand-alone, first-line
      screening test for cervical cancer?

PMID- 25955455
TI  - Corkscrew hairs.

PMID- 25955456
TI  - A 57-year-old woman with abdominal pain.

PMID- 25955457
TI  - Alcoholic hepatitis: Challenges in diagnosis and management.
AB  - Alcoholic hepatitis, in its severe form, is a devastating acute condition that
      requires early recognition and specialized tertiary medical care. This paper
      summarizes its epidemiology, pathophysiology, assessment, and treatment. 

PMID- 25955458
TI  - The Surviving Sepsis Campaign: Where have we been and where are we going?
AB  - The Surviving Sepsis Campaign develops and promotes evidence-based guidelines and
      performance-improvement practices aimed at reducing deaths from sepsis worldwide.
      The most recent guidelines, published in 2013, provide detailed management
      strategies for acute care, fluid resuscitation, and vasopressor use. In addition,
      the campaign has developed simple, short protocols for what to do within 3 and 6
      hours of recognition of sepsis. These protocols are associated with reduced
      mortality rates. 

PMID- 25955459
TI  - Resuming anticoagulation after hemorrhage: A practical approach.
AB  - Most patients who suffer a hemorrhage while on long-term anticoagulant therapy
      continue to be at risk of thrombosis. Physicians often need to reconsider the
      need for anticoagulation in view of the risk of recurrent bleeding, and when
      anticoagulation needs to be resumed, they must also consider the timing and
      strategy. Since there are no evidence-based guidelines for these situations, the
      authors of this paper offer a practical framework for individualizing the
      resumption of anticoagulation after hemorrhage. 

PMID- 25955460
TI  - Domestic violence: it is time for the medical profession to play its part.

PMID- 25955461
TI  - Familial colorectal cancer.
AB  - Identifying individuals with a genetic predisposition to developing familial
      colorectal cancer (CRC) is crucial to the management of the affected individual
      and their family. In order to do so, the physician requires an understanding of
      the different gene mutations and clinical manifestations of familial CRC. This
      review summarises the genetics, clinical manifestations and management of the
      known familial CRC syndromes, specifically Lynch syndrome, familial adenomatous
      polyposis, MUTYH-associated neoplasia, juvenile polyposis syndrome and Peutz
      Jeghers syndrome. An individual suspected of having a familial CRC with an
      underlying genetic predisposition should be referred to a familial cancer centre
      to enable pre-test counselling and appropriate follow up. 

PMID- 25955462
TI  - Consensus guidelines for the investigation and management of encephalitis in
      adults and children in Australia and New Zealand.
AB  - Encephalitis is a complex neurological syndrome caused by inflammation of the
      brain parenchyma. The management of encephalitis is challenging because: the
      differential diagnosis of encephalopathy is broad; there is often rapid disease
      progression; it often requires intensive supportive management; and there are
      many aetiologic agents for which there is no definitive treatment. Patients with
      possible meningoencephalitis are often encountered in the emergency care
      environment where clinicians must consider differential diagnoses, perform
      appropriate investigations and initiate empiric antimicrobials. For patients who
      require admission to hospital and in whom encephalitis is likely, a staged
      approach to investigation and management is preferred with the potential
      involvement of multiple medical specialties. Key considerations in the
      investigation and management of patients with encephalitis addressed in this
      guideline include: Which first-line investigations should be performed?; Which
      aetiologies should be considered possible based on clinical features, risk
      factors and radiological features?; What tests should be arranged in order to
      diagnose the common causes of encephalitis?; When to consider empiric
      antimicrobials and immune modulatory therapies?; and What is the role of brain
      biopsy? 

PMID- 25955463
TI  - Survey of infection control and antimicrobial stewardship practices in Australian
      residential aged-care facilities.
AB  - This study assessed infection prevention and antimicrobial stewardship (AMS)
      practices in Australian residential aged-care facilities (RACF). Two hundred and
      sixty-five surveys (15.6%) were completed with all states represented and the
      majority (177 (67.3%)) privately run. Only 30.6% RACF had infection control
      trained staff on site. Few facilities had AMS policies, only 14% had
      antimicrobial prescribing restrictions. Most facilities offered vaccination to
      residents (influenza vaccination rates >75% in 73% of facilities), but
      pneumococcal vaccination was poor. 

PMID- 25955464
TI  - Long-term follow up of paediatric liver transplant recipients: outcomes following
      transfer to adult healthcare in New Zealand.
AB  - Poor outcomes are reported in young people with chronic health conditions. We
      performed a retrospective notes review of New Zealand paediatric liver transplant
      recipients transferred to adult services. Two patients were lost to follow up.
      Out of 20, 12 were non-adherent, and out of 12, 7 developed rejection. Other risk
      behaviours were common in the non-adherent group. We conclude that dedicated
      services for these young people may be needed to optimise outcomes. 

PMID- 25955465
TI  - Primary central nervous system posttransplantation lymphoproliferative disorder
      after heart and lung transplantation.
AB  - Primary central nervous system posttransplantation lymphoproliferative disorder
      (PCNS-PTLD) is uncommon, especially after heart or lung transplantation. Database
      analysis from a single heart and lung transplantation centre and a literature
      review pertaining to PCNS-PTLD was performed. In this study, the prevalence of
      PCNS-PTLD was 0.18% after heart and/or lung transplants. Of 1674 transplants,
      three cases of PCNS-PTLD developed 14 months, 9 years and 17 years
      posttransplant, and all were Epstein-Barr virus driven malignancies. Literature
      review of the topic revealed predominantly retrospective studies, with most
      reported cases after renal transplantation. The overall survival is poor, and it
      may be improved by early diagnosis and treatment. There are no published
      guidelines on the management of PCNS-PTLD; immune-chemotherapy in conjunction
      with reduction of immune suppression is preferred based on available evidence. 

PMID- 25955467
TI  - Serum creatinine is not the end-all, be-all of renal impairment.

PMID- 25955466
TI  - Bilateral cordotomy post-failure of intrathecal analgesia in a palliative care
      setting.

PMID- 25955468
TI  - Author reply: To PMID 24863630.

PMID- 25955469
TI  - Audit of inpatient referrals.

PMID- 25955470
TI  - Not only monoclonal antibodies...

PMID- 25955471
TI  - Leprosy and Australia.

PMID- 25955472
TI  - Author reply: To PMID 25442759.

PMID- 25955473
TI  - Redesign versus resources: continuity lost.

PMID- 25955474
TI  - Author reply: To PMID 24863137.

PMID- 25955475
TI  - The true prevalence of diabetes in hospital patients and its implications.

PMID- 25955476
TI  - Author reply: To PMID 25070621.

PMID- 25955477
TI  - Systemic lupus erythematosus patients and tertiary specialist care--simple
      considerations dropping through the cracks: osteoporosis monitoring as an
      example.

PMID- 25955478
TI  - Influence of rurality, deprivation and distance from clinic on uptake in men
      invited for abdominal aortic aneurysm screening.
AB  - BACKGROUND: Effective abdominal aortic aneurysm (AAA) screening requires high
      uptake. The aim was to assess the independent association of screening uptake
      with rurality, social deprivation, clinic type, distance to clinic and season.
      METHODS: Screening across Grampian was undertaken by trained nurses in six
      community and three hospital clinics. Men aged 65 years were invited for
      screening by post (with 2 further reminders for non-responders). AAA screening
      data are stored on a national call-recall database. The Scottish postcode
      directory was used to allocate to all invited men a deprivation index (Scottish
      Index of Multiple Deprivation), a Scottish urban/rural category and distance to
      clinic. Multivariable analysis was undertaken. RESULTS: The cohort included 5645
      men invited for screening over 12 months (October 2012 to October 2013); 42.6 per
      cent lived in urban areas, 38.9 per cent in rural areas and 18.5 per cent in
      small towns (uptake 87.0, 89.3 and 90.8 per cent respectively). Overall uptake
      was 88.6 per cent with 76 new AAAs detected: 15.2 (95 per cent c.i. 11.8 to 18.6)
      per 1000 men screened. Aberdeen city (large urban area) had the lowest uptake
      (86.1 per cent). Uptake declined with increasing deprivation, with the steepest
      decline in urban areas. On multivariable analysis, a 1-point increase in
      deprivation deciles was associated with a 0.08 (95 per cent c.i. 0.06 to 0.11)
      reduction in the odds of being screened (P < 0.001). Clinic type (community
      versus hospital), distance to clinic and season were not associated independently
      with uptake. CONCLUSION: Both urban residence and social deprivation were
      associated independently with uptake among men invited for AAA screening.

PMID- 25955479
TI  - Implications of miR166 and miR159 induction to the basal response mechanisms of
      an andigena potato (Solanum tuberosum subsp. andigena) to salinity stress,
      predicted from network models in Arabidopsis.
AB  - MicroRNA (miRNA) mediated changes in gene expression by post-transcriptional
      modulation of major regulatory transcription factors is a potent mechanism for
      integrating growth and stress-related responses. Exotic plants including many
      traditional varieties of Andean potatoes (Solanum tuberosum subsp. andigena) are
      known for better adaptation to marginal environments. Stress physiological
      studies confirmed earlier reports on the salinity tolerance potentials of certain
      andigena cultivars. Guided by the hypothesis that certain miRNAs play important
      roles in growth modulation under suboptimal conditions, we identified and
      characterized salinity stress-responsive miRNA-target gene pairs in the andigena
      cultivar Sullu by parallel analysis of noncoding and coding RNA transcriptomes.
      Inverse relationships were established by the reverse co-expression between two
      salinity stress-regulated miRNAs (miR166, miR159) and their target
      transcriptional regulators HD-ZIP-Phabulosa/Phavulota and Myb101, respectively.
      Based on heterologous models in Arabidopsis, the miR166-HD-ZIP
      Phabulosa/Phavulota network appears to be involved in modulating growth perhaps
      by mediating vegetative dormancy, with linkages to defense-related pathways. The
      miR159-Myb101 network may be important for the modulation of vegetative growth
      while also controlling stress-induced premature transition to reproductive phase.
      We postulate that the induction of miR166 and miR159 under salinity stress
      represents important network hubs for balancing gene expression required for
      basal growth adjustments. 

PMID- 25955480
TI  - Spinal Cord: Series and Cases launched.

PMID- 25955486
TI  - Correction: Out-of-Pocket Costs and Other Determinants of Access to Healthcare
      for Children with Febrile Illnesses: A Case-Control Study in Rural Tanzania.

PMID- 25955488
TI  - Correction: Histone deacetylase inhibition enhances tissue plasminogen activator
      release capacity in atherosclerotic man.

PMID- 25955489
TI  - Membrane-associated virus replication complexes locate to plant conducting tubes.
AB  - It is generally accepted that in order to establish a systemic infection in a
      plant, viruses move from the initially infected cell to the vascular tissues by
      cell-to-cell movement through plasmodesmata (PD), and load into the vascular
      conducting tubes (i.e. phloem sieve elements and xylem vessel elements) for long
      distance movement. The viral unit in these movements can be a virion or a yet-to
      be-defined ribonucleic protein (RNP) complex. Using live-cell imaging, our
      laboratory has previously demonstrated that membrane-bound replication complexes
      move cell-to-cell during turnip mosaic virus (TuMV) infection. Our recent study
      shows that these membrane-bound replication complexes end up in the vascular
      conducting tubes, which is likely the case for potato virus X (PVX) also. The
      presence of TuMV-induced membrane complexes in xylem vessels suggests that viral
      components could also be found in other apoplastic regions of the plant, such as
      the intercellular space. This possibility may have implications regarding how we
      approach the study of plant innate immune responses against viruses. 

PMID- 25955487
TI  - Long-Term Burden and Respiratory Effects of Respiratory Syncytial Virus
      Hospitalization in Preterm Infants-The SPRING Study.
AB  - The health status of premature infants born 321-350 weeks' gestational age (wGA)
      hospitalized for RSV infection in the first year of life (cases; n = 125) was
      compared to that of premature infants not hospitalized for RSV (controls; n =
      362) through 6 years. The primary endpoints were the percentage of children with
      wheezing between 2-6 years and lung function at 6 years of age. Secondary
      endpoints included quality of life, healthcare resource use, and allergic
      sensitization. A significantly higher proportion of cases than controls
      experienced recurrent wheezing through 6 years of age (46.7% vs. 27.4%; p =
      0.001). The vast majority of lung function tests appeared normal at 6 years of
      age in both cohorts. In children with pulmonary function in the lower limit of
      normality (FEV1 Z-score [-2; -1]), wheezing was increased, particularly for cases
      vs. controls (72.7% vs. 18.9%, p = 0.002). Multivariate analysis revealed the
      most important factor for wheezing was RSV hospitalization. Quality of life on
      the respiratory subscale of the TAPQOL was significantly lower (p = 0.001) and
      healthcare resource utilization was significantly higher (p<0.001) in cases than
      controls. This study confirms RSV disease is associated with wheezing in 32-35
      wGA infants through 6 years of age. 

PMID- 25955490
TI  - Zoledronic acid enhances antitumor efficacy of liposomal doxorubicin.
AB  - Previously, we found that the injection of zoledronic acid (ZOL) into mice
      bearing tumor induced changes of the vascular structure in the tumor. In this
      study, we examined whether ZOL treatment could decrease interstitial fluid
      pressure (IFP) via change of tumor vasculature, and enhance the antitumor
      efficacy of liposomal doxorubicin (Doxil(r)). When ZOL solution was injected at
      40 ug/mouse per day for three consecutive days into mice bearing murine Lewis
      lung carcinoma LLC tumor, depletion of macrophages in tumor tissue and decreased
      density of tumor vasculature were observed. Furthermore, ZOL treatments induced
      inflammatory cytokines such as interleukin (IL)-10 and -12, granulocyte
      macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor (TNF)
      alpha in serum of LLC tumor-bearing mice, but not in normal mice, indicating that
      ZOL treatments might induce an inflammatory response in tumor tissue.
      Furthermore, ZOL treatments increased antitumor activity by Doxil in mice bearing
      a subcutaneous LLC tumor, although they did not significantly increase the tumor
      accumulation of doxorubicin (DXR). These results suggest that ZOL treatments
      might increase the therapeutic efficacy of Doxil via improvement of DXR
      distribution in a tumor by changing the tumor vasculature. ZOL treatment can be
      an alternative approach to increase the antitumor effect of liposomal drugs.

PMID- 25955491
TI  - RNF8 plays an important role in the radioresistance of human nasopharyngeal
      cancer cells in vitro.
AB  - Tumor residue or recurrence is common after radiation therapy for nasopharyngeal
      cancer (NPC) since the tumor cells can repair irradiation-induced DNA damage. The
      ubiquitination cascade mediates the assembly of repair and signaling proteins at
      sites of DNA double-strand breaks (DSBs). Ring finger protein 8 (RNF8) is an E3
      ubiquitin ligase that triggers ubiquitination at the site of DSBs. The present
      study aimed to identify whether and how RNF8 small interfering RNA (siRNA)
      treatment enhances the radiosensitivity of irradiated human NPC cell lines. The
      CNE1, CNE2, and SUNE human NPC cell lines were stably transfected with a
      constructed RNF8-targeting siRNA expression vector. Western blotting was used to
      detect the effectiveness of RNF8 downregulation by RNF8 siRNA. The siRNA
      transfected (RNF8-) and non-transfected (RNF8+) cells were irradiated at
      different doses by a linear accelerator. The growth inhibition ratio and
      apoptosis rate were detected by the methyl thiazolyl tetrazolium (MTT) assay and
      flow cytometry, respectively. The ataxia-telangiectasia mutated (ATM), DNA-PKcs,
      Chk1, Chk2, Nbs1 and Ku80 protein levels in each group were determined. The
      growth inhibition ratio and apoptotic percentage of RNF8- cells were higher than
      those of the RNF8+ cells in each of the three cell lines. Lower protein
      expression levels of Chk1, Chk2, ATM, and Nbs1 were observed in the irradiated
      RNF8- cells compared to the irradiated RNF8+ cells in each of the three cell
      lines (P<0.01). As a result, a conclusion could be drawn that RNF8 recruits and
      ubiquitinates many factors to repair DNA damage, including DSBs, thereby
      conferring radioresistance to NPC cells.

PMID- 25955492
TI  - Cancer Stem Cells Sensitivity Assay (STELLA) in Patients with Advanced Lung and
      Colorectal Cancer: A Feasibility Study.
AB  - BACKGROUND: Cancer stem cells represent a population of immature tumor cells
      found in most solid tumors. Their peculiar features make them ideal models for
      studying drug resistance and sensitivity. In this study, we investigated whether
      cancer stem cells isolation and in vitro sensitivity assay are feasible in a
      clinical setting. METHODS: Cancer stem cells were isolated from effusions or
      fresh cancer tissue of 23 patients who progressed after standard therapy failure.
      Specific culture conditions selected for immature tumor cells that express
      markers of stemness. These cells were exposed in vitro to chemotherapeutic and
      targeted agents. RESULTS: Cancer stem cells were extracted from liver metastases
      in 6 cases (25%), lung nodules in 2 (8%), lymph node metastases in 3 (12.5%) and
      pleural/peritoneal/pericardial effusion in 13 (54%). Cancer stem cells were
      successfully isolated in 15 patients (63%), including 14 with lung cancer
      (93.3%). A sensitivity assay was successfully performed in 7 patients (30.4%),
      with a median of 15 drugs/combinations tested (range 5-28) and a median time
      required for results of 51 days (range 37-95). CONCLUSION: The approach used for
      the STELLA trial allowed isolation of cancer stem cells in a consistent
      proportion of patients. The low percentage of cases completing the full procedure
      and the long median time for obtaining results highlights the need for a more
      efficient procedure. TRIAL REGISTRATION: ClinalTrials.gov NCT01483001.

PMID- 25955493
TI  - Isatin based Schiff bases as inhibitors of alpha-glucosidase: Synthesis,
      characterization, in vitro evaluation and molecular docking studies.
AB  - Isatin base Schiff bases (1-20) were synthesized, characterized by (1)H NMR and
      EI/MS and evaluated for alpha-glucosidase inhibitory potential. Out of these
      twenty (20) compounds only six analogs showed potent alpha-glucosidase inhibitory
      potential with IC50 value ranging in between 2.2+/-0.25 and 83.5+/-1.0MUM when
      compared with the standard acarbose (IC50=840+/-1.73MUM). Among the series
      compound 2 having IC50 value (18.3+/-0.56MUM), 9 (83.5+/-1.0MUM), 11 (3.3+/
      0.25MUM), 12 (2.2+/-0.25MUM), 14 (11.8+/-0.15MUM), and 20 (3.0+/-0.15MUM) showed
      excellent inhibitory potential many fold better than the standard acarbose. The
      binding interactions of these active analogs were confirmed through molecular
      docking. 

PMID- 25955494
TI  - Cost-minimization model of a multidisciplinary antibiotic stewardship team based
      on a successful implementation on a urology ward of an academic hospital.
AB  - BACKGROUND: In order to stimulate appropriate antimicrobial use and thereby lower
      the chances of resistance development, an Antibiotic Stewardship Team (A-Team)
      has been implemented at the University Medical Center Groningen, the Netherlands.
      Focus of the A-Team was a pro-active day 2 case-audit, which was financially
      evaluated here to calculate the return on investment from a hospital perspective.
      METHODS: Effects were evaluated by comparing audited patients with a historic
      cohort with the same diagnosis-related groups. Based upon this evaluation a cost
      minimization model was created that can be used to predict the financial effects
      of a day 2 case-audit. Sensitivity analyses were performed to deal with
      uncertainties. Finally, the model was used to financially evaluate the A-Team.
      RESULTS: One whole year including 114 patients was evaluated. Implementation
      costs were calculated to be ?17,732, which represent total costs spent to
      implement this A-Team. For this specific patient group admitted to a urology ward
      and consulted on day 2 by the A-Team, the model estimated total savings of
      ?60,306 after one year for this single department, leading to a return on
      investment of 5.9. CONCLUSIONS: The implemented multi-disciplinary A-Team
      performing a day 2 case-audit in the hospital had a positive return on investment
      caused by a reduced length of stay due to a more appropriate antibiotic therapy.
      Based on the extensive data analysis, a model of this intervention could be
      constructed. This model could be used by other institutions, using their own data
      to estimate the effects of a day 2 case-audit in their hospital.

PMID- 25955495
TI  - Role of the novel HSP90 inhibitor AUY922 in hepatocellular carcinoma: Potential
      for therapy.
AB  - The aim of the present study was to determine the correlation between
      hepatocellular carcinoma (HCC) and heat shock protein 90 (HSP90), involved in
      tumor angiogenesis, and to evaluate the effect of AUY922, a HSP90 inhibitor, in
      HCC. The expression of HSP90 and microvessel density (MVD) were measured in
      tissue samples from 76 patients with HCC by immunohistochemistry. Western blot
      analysis was performed to detect the expression of HSP90 in the HCC tissues and
      different HCC cell lines. The effects of time and concentration treatment with
      the AUY922 HSP90 inhibitor were investigated in HepG2 cells. Cell proliferation
      was measured using an MTT assay and a Transwell assay was performed to evaluate
      the migration of the HepG2 cells following treatment with different
      concentrations of AUY922. Positive staining of HSP90 was observed in 88.16%
      (67/76) of the HCC tissues, compared with 16.67% (4/24) of the normal tissues.
      The difference in the expression of HSP90 between the HCC and normal tissues was
      statistically significant (P<0.001). Tumors exhibiting positive expression of
      HSP90 had significantly higher MVD compared with the HSP90-negative counterparts
      (82.8 +/- 12.44 vs. 23.8 +/- 8.07, respectively; P<0.001). The expression levels
      of HSP90 were positively correlated with MVD in all the tissue samples
      (r_s=0.724; P<0.001). AUY922 inhibited the proliferation of the HepG2 cells in a
      time-and concentration-dependent manner, and the migration of HepG2 cells was
      distinctly suppressed following treatment with AUY922. These data suggested that
      the angiogenesis of human HCC may be mediated by HSP90, and that the specific
      HSP90 inhibitor, AUY922, has a therapeutic role in the treatment of HCC.
      Therefore, HSP90 may represent a selective target in molecularly targeted
      treatment of HCC.

PMID- 25955496
TI  - Inhibiting Notch-1 reduces the expression of Toll-like receptor 9 in BABL/C-lpr
      mouse kidneys and improves glucocorticoid sensitivity.
AB  - Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, characterized
      by the development of a pathogenic autoantibodies. Lupus nephritis is a major
      cause of mortality in patients with SLE. Glucocorticoids are used for the
      treatment of lupus, however, corticosteroids have no effect on the expression of
      Toll-like receptor 9 (TLR9), which may limit response to corticosteroids in
      certain patients with SLR. The expression of TLR9 can be used as a predictor of
      glucocorticoid response in patients with active SLE. The present study analyzed
      urine proteins and pathological kidney sections of BABL/C-lpr mice and found
      that, following the inhibition of Notch1, glucocorticoid treatment improved the
      symptoms of lupus nephritis. Furthermore, glucocorticoid treatment reduced the
      expression of TLR9 in the BABL/C-lpr mouse kidneys, according to
      immunohistochemical and western blot analyses. These results suggested that
      inhibition of the expression of Notch-1 enhanced corticosteroid sensitivity in
      BABL/C-lpr mice.

PMID- 25955497
TI  - Combining GWAS and RNA-Seq Approaches for Detection of the Causal Mutation for
      Hereditary Junctional Epidermolysis Bullosa in Sheep.
AB  - In this study, we demonstrate the use of a genome-wide association mapping
      together with RNA-seq in a reduced number of samples, as an efficient approach to
      detect the causal mutation for a Mendelian disease. Junctional epidermolysis
      bullosa is a recessive genodermatosis that manifests with neonatal mechanical
      fragility of the skin, blistering confined to the lamina lucida of the basement
      membrane and severe alteration of the hemidesmosomal junctions. In Spanish Churra
      sheep, junctional epidermolysis bullosa (JEB) has been detected in two commercial
      flocks. The JEB locus was mapped to Ovis aries chromosome 11 by GWAS and
      subsequently fine-mapped to an 868-kb homozygous segment using the identical-by
      descent method. The ITGB4, which is located within this region, was identified as
      the best positional and functional candidate gene. The RNA-seq variant analysis
      enabled us to discover a 4-bp deletion within exon 33 of the ITGB4 gene
      (c.4412_4415del). The c.4412_4415del mutation causes a frameshift resulting in a
      premature stop codon at position 1472 of the integrin beta4 protein. A functional
      analysis of this deletion revealed decreased levels of mRNA in JEB skin samples
      and the absence of integrin beta4 labeling in immunohistochemical assays.
      Genotyping of c.4412_4415del showed perfect concordance with the recessive mode
      of the disease phenotype. Selection against this causal mutation will now be used
      to solve the problem of JEB in flocks of Churra sheep. Furthermore, the
      identification of the ITGB4 mutation means that affected sheep can be used as a
      large mammal animal model for the human form of epidermolysis bullosa with
      aplasia cutis. Our approach evidences that RNA-seq offers cost-effective
      alternative to identify variants in the species in which high resolution exome
      sequencing is not straightforward. 

PMID- 25955498
TI  - Interhemispheric microstructural connectivity in bitemporal lobe epilepsy with
      hippocampal sclerosis.
AB  - Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy. The most
      frequent pathologic finding in this condition is hippocampal sclerosis (HS). In
      addition, in a small proportion (14-23%) of refractory TLE patients, the presence
      of HS is bilateral. TLE involves grey matter (GM) and white matter (WM)
      abnormalities in a wide cortico-subcortical network. However, the impact of
      neuronal loss on specific WM fiber pathways and associated functional systems as
      well as seizure propagation pathways remains unclear. There is still much
      controversy regarding the role of the commissures (corpus callosum, hippocampal
      commissure and anterior commissure) in interhemispheric seizure propagation. This
      study aimed to investigate the integrity of WM interhemispheric connectivity in a
      singular sample of patients with TLE and bilateral HS using structural magnetic
      resonance imaging (MRI). We performed multimodal structural MRI [high resolution
      T1-weighted and diffusion tensor imaging (DTI)] analyses of seven patients with
      medically refractory TLE with bilateral HS, fourteen unilateral left TLE patients
      and fifteen matched healthy individuals. Whole-brain voxel-wise analysis
      techniques were used. These patients evidenced WM derangement [reduced fractional
      anisotropy (FA), increased mean diffusivity (MD) or reduced WM volume] in
      temporal and extratemporal tracks, but also in commissural pathways, compared to
      the unilateral left TLE patients and the control group. Presence of reduced FA or
      increased MD in the fornix, cingulum and uncinate fasciculus in addition to
      reduced WM volume in the fornix was also encountered. Neuropsychological
      assessment was performed without significant correlations with structural data.
      The current results support the idea that commissural pathways play a
      contributory role in interhemispheric TLE seizure propagation in bilateral HS and
      offer new perspectives about the long-term effects on interhemispheric
      connectivity associated with seizure propagation patterns in TLE patients. 

PMID- 25955499
TI  - Is the logopenic-variant of primary progressive aphasia a unitary disorder?
AB  - Logopenic progressive aphasia is one of the clinical presentations of primary
      progressive aphasia and formally defined by the co-occurrence of impaired naming
      and sentence repetition. Impaired naming is attributed to failure of lexical
      retrieval, which is a multi-staged process subserved by anatomically segregated
      brain regions. By dissecting the neurocognitive processes involved in impaired
      naming, we aimed to disentangle the clinical and neuroanatomical heterogeneity of
      this syndrome. Twenty-one individuals (66.7% females, age range 53-83 years) who
      fulfilled diagnostic criteria for logopenic variant and had at least two clinical
      and language assessments, 1 year apart, were recruited and matched for age, sex
      distribution and level of education with a healthy control sample (n = 18). All
      participants underwent a structural brain scan at the first visit and surface
      wise statistical analysis using Freesurfer. Seventeen participants with logopenic
      variant underwent amyloid imaging, with 14 demonstrating high amyloid retention.
      Based on their performance on single-word comprehension, repetition and
      confrontation naming, three subgroups of logopenic cases with distinctive
      linguistic profiles and distribution of atrophy were identified. The first
      subgroup (n = 10) demonstrated pure anomia and left-sided atrophy in the
      posterior inferior parietal lobule and lateral temporal cortex. The second
      subgroup (n = 6), presented additional mild deficits in single-word
      comprehension, and also exhibited bilateral thinning of the fusiform gyri. The
      third subgroup (n = 5) showed additional impaired single-word repetition, and
      cortical thinning focused on the left superior temporal gyrus. The subgroups
      differed in the proportion of cases with high amyloid retention and in the rate
      of decline of naming performance over time, suggesting that neurodegeneration
      spreads differentially throughout regions subserving word processing. In line
      with previous reports, these results confirm the extensive damage to the language
      network and, in part, explain the clinical heterogeneity observed across
      logopenic cases. 

PMID- 25955501
TI  - Freeze-dried, Capsulized Fecal Microbiota Transplantation for Relapsing
      Clostridium difficile Infection.

PMID- 25955500
TI  - Role of relaxation time scale in noisy signal transduction.
AB  - Intra-cellular fluctuations, mainly triggered by gene expression, are an
      inevitable phenomenon observed in living cells. It influences generation of
      phenotypic diversity in genetically identical cells. Such variation of cellular
      components is beneficial in some contexts but detrimental in others. To quantify
      the fluctuations in a gene product, we undertake an analytical scheme for
      studying few naturally abundant linear as well as branched chain network motifs.
      We solve the Langevin equations associated with each motif under the purview of
      linear noise approximation and derive the expressions for Fano factor and mutual
      information in close analytical form. Both quantifiable expressions exclusively
      depend on the relaxation time (decay rate constant) and steady state population
      of the network components. We investigate the effect of relaxation time
      constraints on Fano factor and mutual information to indentify a time scale
      domain where a network can recognize the fluctuations associated with the input
      signal more reliably. We also show how input population affects both quantities.
      We extend our calculation to long chain linear motif and show that with
      increasing chain length, the Fano factor value increases but the mutual
      information processing capability decreases. In this type of motif, the
      intermediate components act as a noise filter that tune up input fluctuations and
      maintain optimum fluctuations in the output. For branched chain motifs, both
      quantities vary within a large scale due to their network architecture and
      facilitate survival of living system in diverse environmental conditions. 

PMID- 25955502
TI  - Too materialistic to get married and have children?
AB  - We developed new materials to induce a luxury mindset and activate materialistic
      values, and examined materialism's relationship to attitudes toward marriage and
      having children in Singapore. Path analyses indicated that materialistic values
      led to more negative attitudes toward marriage, which led to more negative
      attitudes toward children, which in turn led to a decreased number of children
      desired. Results across two studies highlight, at the individual level, the
      tradeoff between materialistic values and attitudes toward marriage and
      procreation and suggest that a consideration of psychological variables such as
      materialistic values may allow for a better understanding of larger-scale
      socioeconomic issues including low fertility rates among developed countries. We
      discuss implications and describe how psychological factors relating to low
      fertility fit within evolutionary mismatch and life history theory frameworks. 

PMID- 25955503
TI  - Effect of fibrinogen on blood coagulation detected by optical coherence
      tomography.
AB  - Our previous work demonstrated that an optical coherence tomography (OCT)
      technique and the parameter 1/e light penetration depth (d1/e) were able to
      characterize the whole blood coagulation process in contrast to existing optical
      tests that are performed on plasma samples. To evaluate the feasibility of the
      technique for quantifying the effect of fibrinogen (Fbg) on blood coagulation, a
      dynamic study of d1/e of blood in various Fbg concentrations was performed in
      static state. Two groups of blood samples of hematocrit (HCT) in 35, 45, and 55%
      were reconstituted of red blood cells with: 1) treated plasma with its intrinsic
      Fbg removed and commercial Fbg added (0-8 g L(-1)); and 2) native plasma with
      commercial Fbg added (0-8 g L(-1)). The results revealed a typical behavior due
      to coagulation induced by calcium ions and the clotting time is Fbg concentration
      dependent. The clotting time was decreased by the increasing amount of Fbg in
      both groups. Besides, the blood of lower HCT with various levels of Fbg took
      shorter time to coagulate than that of higher HCT. Consequently, the OCT method
      is a useful and promising tool for the detection of blood-coagulation processes
      induced with different Fbg levels. 

PMID- 25955504
TI  - A genotoxic analysis of the hematopoietic system after mobile phone type
      radiation exposure in rats.
AB  - PURPOSE: In our earlier study we reported that 900 MHz continuous wave (CW)
      radiofrequency radiation (RFR) exposure (2 W/kg specific absorption rate [SAR])
      had no significant effect on the hematopoietic system of rats. In this paper we
      extend the scope of the previous study by testing for possible effects at: (i)
      different SAR levels; (ii) both 900 and 1800 MHz, and; (iii) both CW and pulse
      modulated (PM) RFR. MATERIALS AND METHODS: Excised long bones from rats were
      placed in medium and RFR exposed in (i) a Transverse Electromagnetic (TEM) cell
      or (ii) a waveguide. Finite-difference time-domain (FDTD) numerical analyses were
      used to estimate forward power needed to produce nominal SAR levels of 2/10 and
      2.5/12.4 W/kg in the bone marrow. After exposure, the lymphoblasts were extracted
      and assayed for proliferation rate, and genotoxicity. RESULTS: Our data did not
      indicate any significant change in these end points for any combination of CW/PM
      exposure at 900/1800 MHz at SAR levels of nominally 2/10 W/kg or 2.5/12.4 W/kg.
      CONCLUSIONS: No significant changes were observed in the hematopoietic system of
      rats after the exposure of CW/PM wave 900 MHz/1800 MHz RF radiations at different
      SAR values.

PMID- 25955505
TI  - Electrochemical method assisted immobilization and orientation of myoglobin into
      biomimetic brij 56 film and its direct electrochemistry study.
AB  - A simple cyclic voltammetric method was applied to assemble and orient a model
      protein, namely, myoglobin (Mb), into a biocompatible Brij 56 film. Ultraviolet
      visible and circular dichroism spectra indicated that Mb in Brij 56 matrix
      preserved its secondary structure. Fourier transform infrared spectra confirmed
      the formation of hydrogen bonds between Mb and Brij 56. These hydrogen bonds
      acted as the electron tunnel to transfer electrons from Mb's active sites to the
      underlying glassy carbon electrode. Effective direct electron transfer of Mb was
      realized with the presence of a couple of quasi-reversible and well-defined redox
      peaks at -310 mV (vs standard calomel electrode) in the studied potential range.
      The peaks were attributed to the redox couple of heme Fe(II)/Fe(III) of the well
      oriented Mb in Brij 56 matrix. The surface coverage and the electron transfer
      rate (ks) of Mb immobilized into the Brij 56 film was ~4.9*10(-11) mol cm(-2) and
      72.6+/-3.0 s(-1), respectively. An excellent electrocatalytic response of the
      immobilized Mb toward nitrite in the absence of electron transfer mediators was
      observed. These results emphasized that the biomimetic Brij 56 could be used as
      an attractive material for immobilizing proteins and constructing biosensors.

PMID- 25955506
TI  - Synthesis, Structure, Multiband Optical, and Electrical Conductive Properties of
      a 3D Open Cubic Framework Based on [Cu8Sn6S24](z-) Clusters.
AB  - Two compounds with the formulas of Na4Cu32Sn12S48.4H2O and K11Cu32Sn12S48.4H2O
      were synthesized via flux (with thiourea as reactive flux) and hydrothermal
      method, respectively. The black crystals of Na4Cu32Sn12S48.4H2O and
      K11Cu32Sn12S48.4H2O both crystallize in the cubic space group of Fm3c with the
      cell constants a = 17.921(2) A and a = 18.0559(6) A, respectively. The crystal
      structures feature a 3D open-framework with the unique [Cu8Sn6S24](z-) (z = 13
      for Na4Cu32Sn12S48.4H2O; z = 14.75 for K11Cu32Sn12S48.4H2O) clusters acting as
      building blocks. The [Cu8Sn6S24](z-) cluster of the Th symmetry is built up by
      eight [CuS3] triangles and six [SnS4] tetrahedra. The powder samples were
      investigated by X-ray diffraction and optical absorption measurements. Both phase
      pure compounds show multiabsorption character with a main absorption edge (2.0 eV
      for Na4Cu32Sn12S48.4H2O and 1.9 eV for K11Cu32Sn12S48.4H2O) and an additional
      absorption peak (1.61 eV for Na4Cu32Sn12S48.4H2O and 1.52 eV for
      K11Cu32Sn12S48.4H2O), which are perfectly consistent with the first-principle
      calculation results. The analyses of the density of states further reveal that
      the two optical absorption bands in each compound are attributed to the two
      transitions of Cu-3d-S-3p -> Sn-5s. The multiband nature of two compounds also
      enhances photocatalytic activity under visible light irradiation, with which the
      degradation of methyl blue over Na4Cu32Sn12S48.4H2O reached 100% in 3 h. The 3D
      open-framework features also facilitate the ionic conductivity nature of the
      Na4Cu32Sn12S48.4H2O compound, which achieved ~10(-5) S/cm at room temperature. 

PMID- 25955507
TI  - Evaluation of a Shaker Dust Collector for Use in a Recirculating Ventilation
      System.
AB  - General ventilation with recirculated air may be cost-effective to control the
      concentration of low-toxicity, contaminants in workplaces with diffuse, dusty
      operations, such as in agriculture. Such systems are, however, rarely adopted
      with little evidence showing improved air quality and ability to operate under
      harsh conditions. The goal of this work was to examine the initial and long-term
      performance of a fabric-filter shaker dust collector (SDC) in laboratory tests
      and as deployed within a recirculating ventilation system in an agricultural
      building. In laboratory tests, collection efficiency and pressure drop were
      tracked over several filter loading cycles, and the recovery of filter capacity
      (pressure drop) from filter shaking was examined. Collection efficiencies of
      particles larger than 5 MUm was high (>95%) even when the filter was pristine,
      showing effective collection of large particles that dominate inhalable
      concentrations typical of agricultural dusts. For respirable-sized particles,
      collection efficiencies were low when the filter was pristine (e.g., 27% for 1
      MUm) but much higher when a dust cake developed on the filter (>99% for all size
      particles), even after shaking (e.g., 90% for 1 MUm). The first shake of a filter
      was observed to recovery a substantial fraction of filter capacity, with
      subsequent shakes providing little benefit. In field tests, the SDC performed
      effectively over a period of three months in winter when incorporated in a
      recirculating ventilation system of a swine farrowing room. Trends in collection
      efficiency and pressure drop with loading were similar to those observed in the
      laboratory with overall collection efficiencies high (>80%) when pressure drop
      exceeded 230 Pa, or 23% of the maximum loading recommended by the manufacturer.
      This work shows that the SDC can function effectively over the harsh winter in
      swine rearing operations. Together with findings of improved air quality in the
      farrowing room reported in a companion manuscript, this article provides evidence
      that an SDC represents a cost-effective solution to improve air quality in
      agricultural settings. 

PMID- 25955508
TI  - Orbital Cellulitis of Odontogenic Origin.
AB  - Odontogenic orbital cellulitis, although uncommon, has the potential to cause
      severe vision loss if unsuspected and untreated. Compared to non-odontogenic
      bacteriology, odontogenic orbital abscesses typically feature a heavy mixed
      growth with anaerobic organisms. We review the literature and discuss the case of
      a 26-year-old male who presented with anaerobic orbital cellulitis for treatment.

PMID- 25955509
TI  - Recurrent cochlear implant infection treated with exteriorization and partial
      mastoid obliteration.
AB  - OBJECTIVE AND IMPORTANCE: Preoperative chronic otitis media (COM) is a risk
      factor for postoperative infection after cochlear implantation (CI), but its
      management varies by surgeon. Our case highlights a strategy for implant
      preservation in a patient with a history of recurrent cochlear implant infection.
      CLINICAL PRESENTATION: A 70-year-old woman with a history of chronic lymphocytic
      leukemia presented in 2005 with bilateral COM and sensorineural hearing loss
      meeting CI candidacy. Four months after left mastoid obliteration with abdominal
      fat graft and external auditory canal closure, a left CI was placed. Subsequent
      postauricular cellulitis resolved with oral antibiotics. A similar two-stage CI
      was performed on the right without complication. During the following year,
      numerous left-sided infections and fluid collections developed but were treated
      unsuccessfully with intravenous (IV) antibiotics and operative debridement. With
      concern for biofilm colonization, the implant was explanted and the electrode
      left in the cochlea. After reimplantation in 2010, infections resumed despite
      long-term IV antibiotics and incision and drainage. Intervention and technique In
      2012, the left mastoid cavity was exteriorized and converted to standard canal
      wall-down anatomy. Bone pate was placed over the electrode, followed by cadaveric
      acellular dermis and a split-thickness skin graft. After more than 2 years, her
      better-performing CI remains infection-free. CONCLUSION: After 6 years of
      postoperative infections unresponsive to aggressive medical management, surgical
      interventions, and period of device removal, our patient's infections resolved
      after mastoid exteriorization and multilayered protection of the electrode. This
      strategy may enable implant preservation in patients with recurrent post-CI
      infection in an obliterated cavity.

PMID- 25955510
TI  - Effect of cell cycle phase on the sensitivity of SAS cells to sonodynamic therapy
      using low-intensity ultrasound combined with 5-aminolevulinic acid in vitro.
AB  - Sonodynamic therapy (SDT) with 5-aminolevulinic acid (5-ALA) can effectively
      inhibit various types of tumor in vitro and in vivo. However, the association
      between the efficacy of SDT and the phase of the cell cycle remains to be
      elucidated. 5-ALA may generate different quantities of sonosensitizer,
      protoporphyrin IX (PpIX), in different phases of the cell cycle, which may result
      in differences in sensitivity to 5-ALA-induced SDT. The present study aimed to
      investigate the effect of the cell cycle on the susceptibility of SAS cells to
      SDT following synchronization to different cell cycle phases. These results
      indicates that the rates of cell death and apoptosis of the SAS cells in the S
      and G2/M phases were significantly higher following SDT, compared with those in
      the G1-phase cells and unsynchronized cells, with a corresponding increase in
      PpIX in the S and G2/M cells. In addition, the expression of caspase-3 increased,
      while that of B-cell lymphoma (Bcl)-2 decreased markedly in theS and G2/M cells
      following SDT. Cyclin A was also expressed at higher levels in the S and G2/M
      cells, compared with the G1-phase cells. SDT also caused a significant
      upregulation of cyclin A in all phases of the cell cycle, however this was most
      marked in the S and G2/M cells. It was hypothesized that high expression levels
      of cyclin A in the S and G2/M cells may promote the induction of caspase-3 and
      reduce the induction of Bcl-2 by SDT and, therefore, enhance apoptosis. Taken
      together, these data demonstrated that cells in The S and G2/M phases generate
      more intracellular PpIX, have higher levels of cyclin A and are, therefore, more
      sensitive to SDT-induced cytotoxicity. These findings indicate the potential
      novel approach to preventing the onset of cancer by combining cell-cycle
      regulators with SDT. This sequential combination therapy may be a simple and cost
      effective way of enhancing the effects of SDT in clinical settings.

PMID- 25955511
TI  - Role of Chitinase 3-Like-1 in Interleukin-18-Induced Pulmonary Type 1, Type 2,
      and Type 17 Inflammation; Alveolar Destruction; and Airway Fibrosis in the Murine
      Lung.
AB  - Chitinase 3-like 1 (Chi3l1), which is also called YKL-40 in humans and BRP-39 in
      mice, is the prototypic chitinase-like protein. Recent studies have highlighted
      its impressive ability to regulate the nature of tissue inflammation and the
      magnitude of tissue injury and fibroproliferative repair. This can be appreciated
      in studies that highlight its induction after cigarette smoke exposure, during
      which it inhibits alveolar destruction and the genesis of pulmonary emphysema. IL
      18 is also known to be induced and activated by cigarette smoke, and, in murine
      models, the IL-18 pathway has been shown to be necessary and sufficient to
      generate chronic obstructive pulmonary disease-like inflammation, fibrosis, and
      tissue destruction. However, the relationship between Chi3l1 and IL-18 has not
      been defined. To address this issue we characterized the expression of Chi3l1/BRP
      39 in control and lung-targeted IL-18 transgenic mice. We also characterized the
      effects of transgenic IL-18 in mice with wild-type and null Chi3l1 loci. The
      former studies demonstrated that IL-18 is a potent stimulator of Chi3l1/BRP-39
      and that this stimulation is mediated via IFN-gamma-, IL-13-, and IL-17A
      dependent mechanisms. The latter studies demonstrated that, in the absence of
      Chi3l1/BRP-39, IL-18 induced type 2 and type 17 inflammation and fibrotic airway
      remodeling were significantly ameliorated, whereas type 1 inflammation,
      emphysematous alveolar destruction, and the expression of cytotoxic T lymphocyte
      perforin, granzyme, and retinoic acid early transcript 1 expression were
      enhanced. These studies demonstrate that IL-18 is a potent stimulator of Chi3l1
      and that Chi3l1 is an important mediator of IL-18-induced inflammatory, fibrotic,
      alveolar remodeling, and cytotoxic responses. 

PMID- 25955512
TI  - Implementation of an electronic health records system within an interprofessional
      model of care.
AB  - Implementation of electronic health records (EHR) systems is challenging even in
      traditional healthcare settings, where administrative and clinical roles and
      responsibilities are clearly defined. However, even in these traditional settings
      the conflicting needs of stakeholders can trigger hierarchical decision-making
      processes that reflect the traditional power structures in healthcare today.
      These traditional processes are not structured to allow for incorporation of new
      patient-care models such as patient-centered care and interprofessional teams.
      New processes for EHR implementation and evaluation will be required as
      healthcare shifts to a patient-centered model that includes patients, families,
      multiple agencies, and interprofessional teams in short- and long-term clinical
      decision-making. This new model will be enabled by healthcare information
      technology and defined by information flow, workflow, and communication needs. We
      describe a model in development for the configuration and implementation of an
      EHR system in an interprofessional, interagency, free-clinic setting. The model
      uses a formative evaluation process that is rooted in usability to configure the
      EHR to fully support the needs of the variety of providers working as an
      interprofessional team. For this model to succeed, it must include informaticists
      as equal and essential members of the healthcare team. 

PMID- 25955513
TI  - Biomechanical Effects of Stiffness in Parallel With the Knee Joint During
      Walking.
AB  - The human knee behaves similarly to a linear torsional spring during the stance
      phase of walking with a stiffness referred to as the knee quasi-stiffness. The
      spring-like behavior of the knee joint led us to hypothesize that we might
      partially replace the knee joint contribution during stance by utilizing an
      external spring acting in parallel with the knee joint. We investigated the
      validity of this hypothesis using a pair of experimental robotic knee
      exoskeletons that provided an external stiffness in parallel with the knee joints
      in the stance phase. We conducted a series of experiments involving walking with
      the exoskeletons with four levels of stiffness, including 0%, 33%, 66%, and 100%
      of the estimated human knee quasi-stiffness, and a pair of joint-less replicas.
      The results indicated that the ankle and hip joints tend to retain relatively
      invariant moment and angle patterns under the effects of the exoskeleton mass,
      articulation, and stiffness. The results also showed that the knee joint responds
      in a way such that the moment and quasi-stiffness of the knee complex (knee joint
      and exoskeleton) remains mostly invariant. A careful analysis of the knee moment
      profile indicated that the knee moment could fully adapt to the assistive moment;
      whereas, the knee quasi-stiffness fully adapts to values of the assistive
      stiffness only up to ~80%. Above this value, we found biarticular consequences
      emerge at the hip joint. 

PMID- 25955514
TI  - Designing nanomaterials to maximize performance and minimize undesirable
      implications guided by the Principles of Green Chemistry.
AB  - The Twelve Principles of Green Chemistry were first published in 1998 and provide
      a framework that has been adopted not only by chemists, but also by design
      practitioners and decision-makers (e.g., materials scientists and regulators).
      The development of the Principles was initially motivated by the need to address
      decades of unintended environmental pollution and human health impacts from the
      production and use of hazardous chemicals. Yet, for over a decade now, the
      Principles have been applied to the synthesis and production of engineered
      nanomaterials (ENMs) and the products they enable. While the combined efforts of
      the global scientific community have led to promising advances in the field of
      nanotechnology, there remain significant research gaps and the opportunity to
      leverage the potential global economic, societal and environmental benefits of
      ENMs safely and sustainably. As such, this tutorial review benchmarks the
      successes to date and identifies critical research gaps to be considered as
      future opportunities for the community to address. A sustainable material design
      framework is proposed that emphasizes the importance of establishing structure
      property-function (SPF) and structure-property-hazard (SPH) relationships to
      guide the rational design of ENMs. The goal is to achieve or exceed the
      functional performance of current materials and the technologies they enable,
      while minimizing inherent hazard to avoid risk to human health and the
      environment at all stages of the life cycle. 

PMID- 25955515
TI  - Nickel-Catalyzed Formation of Fluorine-Containing Ketones via the Selective Cross
      Trimerization Reaction of Tetrafluoroethylene, Ethylene, and Aldehydes.
AB  - In the presence of a catalytic amount of Ni(cod)2 and IPr (1,3-bis(2,6
      diisopropylphenyl)imidazol-2-ylidene), a cross-trimerization reaction of
      tetrafluoroethylene (TFE), ethylene, and aldehydes proceeded in a selective
      manner to afford a variety of 4,4,5,5-tetrafluoro-1-pentanone derivatives in good
      to excellent yields. The present system involves a five-membered nickelacycle key
      intermediate generated via the oxidative cyclization of TFE and ethylene. 

PMID- 25955516
TI  - Moving-window two-dimensional heterospectral (MW2DHetero) correlation analysis
      and its application for the process monitoring of alcoholic fermentation.
AB  - The technique of moving-window two-dimensional heterospectral (MW2DHetero)
      correlation spectroscopy is proposed. This computational method is based on the
      ideas of perturbation-correlation moving-window two-dimensional (PCMW2D)
      correlation spectroscopy and two-dimensional heterospectral correlation analysis.
      Not only small spectral variations, but also detailed bands assignments were
      captured using the analysis. This method was applied to near-infrared (NIR)
      spectra in the 10 000-4000 cm(-1) region and mid-infrared (mid-IR) spectra in the
      5000-1200 cm(-1) region, which were simultaneously detected using a dual-region
      spectrometer. Near-infrared and mid-IR spectra collected during an alcoholic
      fermentation process using a solution containing glucose and fructose were
      reported. Slight time differences for the consumption of sugars compared with the
      production of ethanol were found between 50 and 150 min. It was concluded that
      these slight time differences are evidence for different consumption times
      between glucose and fructose during the fermentation process. The result proved a
      possibility of the selective monitoring of the simultaneous reaction processes
      between productive and consumptive components. 

PMID- 25955517
TI  - Household Contact Screening Adherence among Tuberculosis Patients in Northern
      Ethiopia.
AB  - BACKGROUND: Household contacts of active tuberculosis cases are at high risk of
      getting tuberculosis disease. Tuberculosis detection rate among contacts of
      household members is high. Hence, this study investigated household contact
      screening adherence and associated factors among tuberculosis patients in Amhara
      region, Ethiopia. METHODS: A cross-sectional study was conducted from April 10 -
      June 30, 2013 in five urban districts of Amhara region, where 418 patients
      receiving treatment at tuberculosis clinic were interviewed. All patients were
      interviewed using structured and pre-tested questionnaire. Bringing at least one
      household contact to TB clinic was regarded as adherent to household contacts
      screening. Bivariate and multiple logistic regressions were used to investigate
      association. RESULTS: The overall adherence to household contact screening in
      Amhara region was 33.7%. Adherence was higher among Muslims than Christians.
      Adherence was high if patient took health education from Health Care Worker [AOR:
      3.22, 95% CI: 1.88 to 5.51] and 2.17 times higher if patient had sufficient
      knowledge on tuberculosis [AOR: 2.17, 95% CI: 1.29 to 3.67] during interview.
      Relationship with contact was a significant [AOR: 0.4, 95% CI: 0.2 to 0.9] social
      related factor. CONCLUSION: One third of tuberculosis patients adhered to
      household contact screening in health facilities during their treatment course.
      Promoting knowledge of tuberculosis in the community and continuous health
      education to tuberculosis patients are recommended.

PMID- 25955520
TI  - Duane retraction syndrome type 1 with Usher syndrome type 2: an unreported
      association.
AB  - Duane retraction syndrome is characterized by globe retraction and palpebral
      fissure narrowing on adduction, with restriction of abduction, adduction, or
      both. Usher syndrome type 2 consists of congenital bilateral sensorineural
      hearing loss and retinitis pigmentosa. The authors present a case with a yet
      unreported association between Duane retraction syndrome type 1 and Usher
      syndrome type 2.

PMID- 25955521
TI  - Early Detection of Infection in Pigs through an Online Monitoring System.
AB  - Late detection of emergency diseases causes significant economic losses for pig
      producers and governments. As the first signs of animal infection are usually
      fever and reduced motion that lead to reduced consumption of water and feed, we
      developed a novel smart system to monitor body temperature and motion in real
      time, facilitating the early detection of infectious diseases. In this study,
      carried out within the framework of the European Union research project Rapidia
      Field, we tested the smart system on 10 pigs experimentally infected with two
      doses of an attenuated strain of African swine fever. Biosensors and an
      accelerometer embedded in an eartag captured data before and after infection, and
      video cameras were used to monitor the animals 24 h per day. The results showed
      that in 8 of 9 cases, the monitoring system detected infection onset as an
      increase in body temperature and decrease in movement before or simultaneously
      with fever detection based on rectal temperature measurement, observation of
      clinical signs, the decrease in water consumption or positive qPCR detection of
      virus. In addition, this decrease in movement was reliably detected using
      automatic analysis of video images therefore providing an inexpensive alternative
      to direct motion measurement. The system can be set up to alert staff when high
      fever, reduced motion or both are detected in one or more animals. This system
      may be useful for monitoring sentinel herds in real time, considerably reducing
      the financial and logistical costs of periodic sampling and increasing the
      chances of early detection of infection.

PMID- 25955518
TI  - Fine Mapping of a GWAS-Derived Obesity Candidate Region on Chromosome 16p11.2.
AB  - INTRODUCTION: Large-scale genome-wide association studies (GWASs) have identified
      97 chromosomal loci associated with increased body mass index in population-based
      studies on adults. One of these SNPs, rs7359397, tags a large region (approx.
      1MB) with high linkage disequilibrium (r2>0.7), which comprises five genes
      (SH2B1, APOBR, sulfotransferases: SULT1A1 and SULT1A2, TUFM). We had previously
      described a rare mutation in SH2B1 solely identified in extremely obese
      individuals but not in lean controls. METHODS: The coding regions of the genes
      APOBR, SULT1A1, SULT1A2, and TUFM were screened for mutations (dHPLC, SSCP,
      Sanger re-sequencing) in 95 extremely obese children and adolescents. Detected
      non-synonymous variants were genotyped (TaqMan SNP Genotyping, MALDI TOF, PCR
      RFLP) in independent large study groups (up to 3,210 extremely obese/overweight
      cases, 485 lean controls and 615 obesity trios). In silico tools were used for
      the prediction of potential functional effects of detected variants. RESULTS:
      Except for TUFM we detected non-synonymous variants in all screened genes. Two
      polymorphisms rs180743 (APOBR p.Pro428Ala) and rs3833080 (APOBR
      p.Gly369_Asp370del9) showed nominal association to (extreme) obesity (uncorrected
      p = 0.003 and p = 0.002, respectively). In silico analyses predicted a functional
      implication for rs180743 (APOBR p.Pro428Ala). Both APOBR variants are located in
      the repetitive region with unknown function. CONCLUSION: Variants in APOBR
      contributed as strongly as variants in SH2B1 to the association with extreme
      obesity in the chromosomal region chr16p11.2. In silico analyses implied no
      functional effect of several of the detected variants. Further in vitro or in
      vivo analyses on the functional implications of the obesity associated variants
      are warranted.

PMID- 25955519
TI  - Sulfiredoxin-1 exerts anti-apoptotic and neuroprotective effects against
      oxidative stress-induced injury in rat cortical astrocytes following exposure to
      oxygen-glucose deprivation and hydrogen peroxide.
AB  - Sulfiredoxin 1 (Srxn1), an endogenous antioxidant protein, plays an important
      neuroprotective role in cerebral ischemia. However, the exact mechanisms of
      action of Srxn1 in cerebral ischemia have not yet been fully elucidated.
      Therefore, in the present study, rat primary cortical astrocytes transfected with
      a lentiviral vector encoding short hairpin RNA (shRNA) were exposed to oxygen
      glucose deprivation (OGD) for 4 h or to 100 uM hydrogen peroxide (H2O2) for 6 h,
      in order to construct an in vitro model of cerebral ischemia-induced damage. We
      found that following exposure to OGD or H2O2, the knockdown of Srxn1 resulted in
      a decrease in cell viability, as shown by MTS assay, an increase in cell damage,
      as shown by lactate dehydrogenase assay and an increase in cellular apoptosis, as
      shown by Hoechst 33342 staining and flow cytometry. Furthermore, we found that
      following exposure to OGD or H2O2, the knockdown of Srxn1 resulted in a decrease
      in mitochondrial transmembrane potential (Deltapsim) as indicated by JC-1
      staining, an increase in the cytoplasmic expression of cytochrome c (Cyt.C),
      caspase-3, caspase-9, poly(ADP-ribose) polymerase (PARP) and Bax protein at the
      protein level, but a decrease in the expression of the anti-apoptotic Bcl-2
      protein; these effects were tightly associated with the mitochondrial apoptotic
      pathway. However, we found that there was no obvious change in the intracellular
      calcium ([Ca2+]i) levels and caspase-12 expression following the knockdown of
      Srxn1. Taken together, the results from the present study demonstrate that Srxn1
      protects primary rat cortical astrocytes from OGD- or H2O2-induced apoptosis and
      that involves the activation of the mitochondrial apoptotic pathway, which
      suggests that Srxn1 may be a potential target in the treatment of cerebral
      ischemia.

PMID- 25955523
TI  - Is choline PET useful for identifying intraprostatic tumour lesions? A literature
      review.
AB  - More than 80% of patients with intermediate-risk or high-risk localized prostate
      cancer are cured with radiation doses of 74-78 Gy, but high doses increase the
      risk for late bowel and bladder toxicity among long-term survivors. Dose
      painting, defined as dose escalation to areas in the prostate containing the
      tumour, rather than to the whole gland, minimizes dose to normal tissues and
      hence toxicity. It requires accurate identification of the location and size of
      these lesions, for which functional MRI is the current gold standard. Many
      studies have assessed the use of choline PET in staging newly diagnosed patients.
      This review will discuss important imaging variables affecting the accuracy of
      choline PET scans, how choline PET contributes to tumour identification and is
      used in radiotherapy planning and how PET can improve the patient pathway
      involving prostate radiotherapy. In summary, the available literature shows that
      the accuracy of choline PET improves with higher tracer doses and delayed imaging
      (although the optimal uptake time is unclear), and tumour identification by MRI
      is improved by the addition of PET imaging. We propose future research with
      prolonged choline uptake time and multiphase imaging, which may further improve
      accuracy.

PMID- 25955522
TI  - Prevalence of bacterial febrile illnesses in children in Kilosa district,
      Tanzania.
AB  - INTRODUCTION: Bacterial etiologies of non-malaria febrile illnesses have
      significantly become important due to high mortality and morbidity, particularly
      in children. Despite their importance, there are few reports on the epidemiology
      of these diseases in Tanzania, and the true burden of such illnesses remains
      unknown. This study aimed to identify the prevalence of leptospirosis,
      brucellosis, typhoid fever and urinary tract infections and their rate of co
      infections with malaria. METHODS: A cross-sectional study was conducted at Kilosa
      district hospital in Tanzania for 6 months. Febrile children aged from 2-13 years
      were recruited from the outpatient department. Patients were screened by
      serological tests such as IgM and IgG ELISA, and microscopic agglutination test.
      RESULTS: A total of 370 patients were enrolled; of these 85 (23.0%) had malaria
      parasites, 43 (11.6%) had presumptive acute leptospirosis and 26/200 (13%) had
      confirmed leptospirosis. Presumptive acute brucellosis due to B. abortus was
      identified among 26 (7.0%) of patients while B. melitensis was detected in 57
      (15.4%) of the enrolled patients. Presumptive typhoid fever due to S. Typhi was
      identified in thirty eight (10.3%) of the participants and 69 (18.6%) had urinary
      tract infections. Patients presented with similar symptoms; therefore, the
      identification of these diseases could not be done based on clinical ground
      alone. Co-infections between malaria and bacterial febrile illnesses were
      observed in 146 patients (39.5%). Although antibacterials and/or anti-malarials
      were prescribed in most patients, some patients did not receive the appropriate
      treatment. CONCLUSION: The study has underscored the importance of febrile
      bacterial diseases including zoonoses such as leptospirosis and brucellosis in
      febrile children, and thus such illnesses should be considered by clinicians in
      the differential diagnoses of febrile diseases. However, access to diagnostic
      tests for discrimination of febrile illnesses is needed. This would allow febrile
      patients to receive the correct diagnoses and facilitation of accurate and prompt
      treatment.

PMID- 25955524
TI  - 4,5-cis unsaturated alpha-GalCer analogues distinctly lead to CD1d-mediated Th1
      biased NKT cell responses.
AB  - The total synthesis of 4,5-cis unsaturated alpha-GalCer analogues was achieved,
      and their immune-response altering activity was assessed in vitro as well as in
      vivo in mice. Using glycosyl iodide as a glycosyl donor, construction of the
      sphingosine unit was shortened by four steps and single alpha-stereoselectivity
      was achieved in good yield (67%). With regard to the therapeutic use of alpha
      GalCer, the novel analogues (1b and 1c) distinctly induced a Th1-biased cytokine
      response, avoiding induction of a contradictory response and overstimulation.

PMID- 25955526
TI  - An Assessment of Indoor Air Quality before, during and after Unrestricted Use of
      E-Cigarettes in a Small Room.
AB  - Airborne chemicals in the indoor environment arise from a wide variety of sources
      such as burning fuels and cooking, construction materials and furniture,
      environmental tobacco smoke as well as outdoor sources. To understand the
      contribution of exhaled e-cigarette aerosol to the pre-existing chemicals in the
      ambient air, an indoor air quality study was conducted to measure volatile
      organic compounds (including nicotine and low molecular weight carbonyls),
      polycyclic aromatic hydrocarbons, tobacco-specific nitrosamines and trace metal
      levels in the air before, during and after e-cigarette use in a typical small
      office meeting room. Measurements were compared with human Health Criteria
      Values, such as indoor air quality guidelines or workplace exposure limits where
      established, to provide a context for potential bystander exposures. In this
      study, the data suggest that any additional chemicals present in indoor air from
      the exhaled e-cigarette aerosol, are unlikely to present an air quality issue to
      bystanders at the levels measured when compared to the regulatory standards that
      are used for workplaces or general indoor air quality. 

PMID- 25955527
TI  - Trends in infant mortality in United States: a brief study of the Southeastern
      states from 2005-2009.
AB  - While overall infant mortality rates have declined over the past several decades,
      the Southeastern states have remained the leading states in high infant death in
      the United States. In this study, we studied the differences in infant mortality
      in the southeastern United States from 2005 through 2009 according to mother's
      characteristics (age of mother, marital status, maternal race, maternal
      education), birth characteristics (month when maternal prenatal care began, birth
      weight), and infant's characteristics (age of infant at death). This paper
      illustrates the significance level of each characteristic of mothers and infants,
      as well as socioeconomic factors that contribute to significant infant mortality
      that impacts subgroups within the US population. Descriptive statistics and
      analysis of variance studies were performed and presented. Statistical analysis
      of the contribution of causes of infant death to infant mortality at the national
      and state level was elaborated. Data suggest that mothers with no prenatal care
      had a very high overall infant death rate (5281.83 and 4262.16 deaths per 100,000
      births in Mississippi and Louisiana, respectively, whereas the US average was
      3074.82 deaths (p < 0.01)). It is suggested that better education and living
      quality should be available and improved for the residents in Alabama, Louisiana,
      and Mississippi. 

PMID- 25955525
TI  - Epigallocatechin 3-gallate ameliorates bile duct ligation induced liver injury in
      mice by modulation of mitochondrial oxidative stress and inflammation.
AB  - Cholestatic liver fibrosis was achieved by bile duct ligation (BDL) in mice.
      Liver injury associated with BDL for 15 days included significant reactive
      oxygen/nitrogen species generation, liver inflammation, cell death and fibrosis.
      Administration of Epigallocatechin 3-Gallate (EGCG) in animals reduced liver
      fibrosis involving parenchymal cells in BDL model. EGCG attenuated BDL-induced
      gene expression of pro-fibrotic markers (Collagen, Fibronectin, alpha 2 smooth
      muscle actin or SMA and connective tissue growth factor or CTGF), mitochondrial
      oxidative stress, cell death marker (DNA fragmentation and PARP activity),
      NFkappaB activity and pro-inflammatory cytokines (TNFalpha, MIP1alpha, IL1beta,
      and MIP2). EGCG also improved BDL induced damages of mitochondrial electron
      transport chain complexes and antioxidant defense enzymes such as glutathione
      peroxidase and manganese superoxide dismutase. EGCG also attenuated hydrogen
      peroxide induced cell death in hepatocytes in vitro and alleviate stellate cells
      mediated fibrosis through TIMP1, SMA, Collagen 1 and Fibronectin in vitro. In
      conclusion, the reactive oxygen/nitrogen species generated from mitochondria
      plays critical pathogenetic role in the progression of liver inflammation and
      fibrosis and this study indicate that EGCG might be beneficial for reducing liver
      inflammation and fibrosis. 

PMID- 25955528
TI  - Molecular detection of a potentially toxic diatom species.
AB  - A few diatom species produce toxins that affect human and animal health. Among
      these, members of the Pseudo-nitzschia genus were the first diatoms unambiguously
      identified as producer of domoic acid, a neurotoxin affecting molluscan shell
      fish, birds, marine mammals, and humans. Evidence exists indicating the
      involvement of another diatom genus, Amphora, as a potential producer of domoic
      acid. We present a strategy for the detection of the diatom species Amphora
      coffeaeformis based on the development of species-specific oligonucleotide probes
      and their application in microarray hybridization experiments. This approach is
      based on the use of two marker genes highly conserved in all diatoms, but endowed
      with sufficient genetic divergence to discriminate diatoms at the species level.
      A region of approximately 450 bp of these previously unexplored marker genes,
      coding for elongation factor 1-a (eEF1-a) and silicic acid transporter (SIT), was
      used to design oligonucleotide probes that were tested for specificity in
      combination with the corresponding fluorescently labeled DNA targets. The results
      presented in this work suggest a possible use of this DNA chip technology for the
      selective detection of A. coffeaeformis in environmental settings where the
      presence of this potential toxin producer may represent a threat to human and
      animal health. In addition, the same basic approach can be adapted to a wider
      range of diatoms for the simultaneous detection of microorganisms used as
      biomarkers of different water quality levels. 

PMID- 25955529
TI  - Ninety day toxicity and toxicokinetics of fluorochloridone after oral
      administration in rats.
AB  - The ninety day toxicity and toxicokinetics of fluorochloridone (FLC) were
      accessed in Wistar rats. Animals were gavaged with FLC at doses of 31.25 mg/kg,
      125 mg/kg and 500 mg/kg for ninety days, followed by thirty days for recovery. On
      the 1st, 60th, 75th and 90th days of the dosing phase, plasma of ten animals of
      all groups treated with FLC was collected for toxicokinetic analysis of FLC by an
      UPLC-MS/MS method. Numerous changes in body weight, hematology, serum chemistry,
      and organ weight ratios were observed by the 45th and 90th dosing day. Most
      changes in groups treated with FLC were absent on the last recovery day. Testis
      and epididymis lesions were consistently seen in histopathological observations
      on the 45th, 90th dosing day and the last recovery day. Repeated administration
      of FLC increased the level of testosterone in serum in male rats on the 90th
      dosing day. FLC plasma concentrations could be detected in all animal drug
      treated groups during the dosing phase, and a dose proportional relationship was
      seen between FLC dose and AUC or Cmax. This study will support future studies on
      the mechanism of FLC-induced toxicity. 

PMID- 25955530
TI  - Intraurban and longitudinal variability of classical pollutants in Krakow,
      Poland, 2000-2010.
AB  - In spite of a dramatic decrease in anthropogenic emissions, ambient
      concentrations of major pollutants have not changed within many urban locations.
      To clarify the relationship between ambient air quality trend and the population
      exposures, we compared the intraurban versus temporal variability of the
      collocated measurements of five major air pollutants including particulate matter
      (PM) with an aerodynamic diameter <10 um (PM10), < 2.5 um (PM2.5), tropospheric
      ozone (O3), sulfur dioxide (SO2), and nitrogen dioxide (NO2), in Krakow, Poland,
      during the 2000-2010 period. Strong seasonal trends and overall absence of
      spatial heterogeneity in PM10 and PM2.5, except in the traffic monitoring site,
      were observed across the monitoring network. The range of median PM2.5
      concentrations during winter (54-64 ug/m3) was 3- to 4-times higher than the
      summer medians (15-26 ug/m3) across the sites during 2009-2010. Furthermore,
      large proportion of PM10 appears to be comprised of PM2.5 (PM2.5/PM10
      concentration ratios range, 0.5-0.7). At each monitoring site, the Pearson's
      correlation coefficients between PM2.5 and PM10 ranged between 0.944 and 0.963,
      suggesting a health-relevance of PM10 monitoring. One ln-unit increase in PM10
      was associated with 92%-100% increase in PM2.5 concentrations in the same
      location. While PM10 did not demonstrate a clear temporal trend, SO2
      concentrations steadily declined by 40% during the 2000-2010 period. Summertime
      median NO2 concentration was acutely elevated (70 mg/m3 vs. 22 mg/m3) at the
      traffic oriented site compared to the city's central monitoring site. The traffic
      and the industrial sites were associated with highest number of days during which
      24-hour mean PM10 and PM2.5 concentrations exceeded the European Union standard.
      Steadily growing contributions by vehicular emissions appear to be associated
      with the absence of clear trend in PM10. Current practices of air quality control
      within Krakow may not be adequate for the protection of the public's health.

PMID- 25955531
TI  - Extremely reduced motion in front of screens: investigating real-world physical
      activity of adolescents by accelerometry and electronic diary.
AB  - This paper reports accelerometer and electronic dairy data on typical daily
      activities of 139 school students from grade six and nine. Recordings covered a
      typical school day for each student and lasted on average for 23 h. Screen
      activities (watching television and using the computer) are compared to several
      other activities performed while sitting (e.g., playing, eating, sitting in
      school, and doing homework). Body movement was continuously recorded by four
      accelerometers and transformed into a motion sore. Our results show that
      extremely low motion scores, as if subjects were freezing, emerge to a greater
      extent in front of screens compared to other investigated activities. Given the
      substantial amount of time young people spend in front of screens and the rising
      obesity epidemic, our data suggest a mechanism for the association of screen time
      and obesity. 

PMID- 25955534
TI  - Gartanin induces autophagy through JNK activation which extenuates caspase
      dependent apoptosis.
AB  - Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death
      worldwide. Development of novel agents to eradicate liver cancer cells is
      required for treatment of HCC. Gartanin, a xanthone-type compound isolated from
      mangosteen, is known to possess potent antioxidant, anti-inflammatory, antifungal
      and antineoplastic properties. In the present study, we investigated the
      cytotoxic effect of gartanin on HCC and explored the cell death mechanism. We
      showed that gartanin induced both the extrinsic and intrinsic apoptotic pathways,
      which were interconnected by caspase-8, -9 and -3 activation. We also provided
      convincing evidence that gartanin induced autophagy in various cancer cells, as
      demonstrated by acridine orange staining of intracellular acidic vesicles, the
      degradation of p62, the conversion of LC3-I to LC3-II and GFP-LC3 punctate
      fluorescence. Additionally, gartanin induced the formation of typical
      autophagosomes and autolysosomes and enhanced the degradation rate of
      intracellular granule(s), including mitochondria. Notably, gartanin-mediated
      apoptotic cell death was further potentiated by pretreatment with autophagy
      inhibitors (3-methyladenine and bafilomycin A1) or small interfering RNAs against
      the autophagic genes (Atg5). These findings suggested that gartanin-mediated
      autophagic response protected against eventual cell death induced by gartanin.
      Moreover, gartanin treatment led to phosphorylation/activation of JNK and JNK
      dependent phosphorylation of Bcl-2. Importantly, JNK inhibitor (SP600125)
      inhibited autophagy yet promoted gartanin-induced apoptosis, indicating a key
      requirement of the JNK-Bcl-2 pathway in the activation of autophagy by gartanin.
      Taken together, our data suggested that the JNK-Bcl-2 pathway was the critical
      regulator of gartanin-induced protective autophagy and a potential drug target
      for chemotherapeutic combination.

PMID- 25955533
TI  - Therapeutic effects of Lactobacillus casei Qian treatment in activated carbon
      induced constipated mice.
AB  - In the present study, the therapeutic effects of Lactobacillus casei Qian (LC
      Qian), the key microorganism in Tibetan yak yoghurt, on activated carbon-induced
      constipation were determined in vivo. ICR mice were treated with LC-Qian for nine
      days by oral administration. The body weight, defecation status, gastrointestinal
      transit and defecation time of mice were assessed, and the serum levels of
      motilin (MTL), gastrin (Gas), endothelin (ET), somatostatin (SS),
      acetylcholinesterase (AChE), substance P (SP) and vasoactive intestinal peptide
      (VIP) were further evaluated. Bisacodyl was used as the positive control. The
      time until the first black stool defecation following carbon intake of the
      normal, control, 100 mg/kg bisacodyl-treated, Lactobacillus bulgaricus (LB)
      treated, LC-Qian (L)-and LC-Qian (H)-treated mice was 93, 231, 121, 194, 172 and
      157 min, respectively. Following treatment with LC-Qian, the gastrointestinal
      transit was increased to 52.4% [LC-Qian (L)] and 65.8% [LC-Qian (H)], while that
      in the group treated with the common lactic acid bacteria of LB was 40.3%. The
      MTL, Gas, ET, AChE, SP and VIP serum levels were significantly increased and
      levels of SS were reduced in mice following LC-Qian treatment compared with those
      in the control mice (P<0.05). Reverse transcription quantitative polymerase chain
      reaction indicated that LC-Qian raised the c-Kit, GDNF as well as SCF mRNA
      expression levels and reduced the TRPV1 and NOS expression levels in tissue of
      the small intestine in mice. These results suggested that lactic acid bacteria
      prevent constipation in mice, among which LC-Qian was the most effective.

PMID- 25955532
TI  - Increased Expression of TGF-beta Signaling Components in a Mouse Model of
      Fibrosis Induced by Submandibular Gland Duct Ligation.
AB  - Transforming growth factor-beta (TGF-beta) is a multi-functional cytokine with a
      well-described role in the regulation of tissue fibrosis and regeneration in the
      liver, kidney and lung. Submandibular gland (SMG) duct ligation and subsequent
      deligation in rodents is a classical model for studying salivary gland damage and
      regeneration. While previous studies suggest that TGF-beta may contribute to
      salivary gland fibrosis, the expression of TGF-beta signaling components has not
      been investigated in relation to mouse SMG duct ligation-induced fibrosis and
      regeneration following ductal deligation. Following a 7 day SMG duct ligation,
      TGF-beta1 and TGF-beta3 were significantly upregulated in the SMG, as were TGF
      beta receptor 1 and downstream Smad family transcription factors in salivary
      acinar cells, but not in ductal cells. In acinar cells, duct ligation also led to
      upregulation of snail, a Smad-activated E-cadherin repressor and regulator of
      epithelial-mesenchymal transition, whereas in ductal cells upregulation of E
      cadherin was observed while snail expression was unchanged. Upregulation of these
      TGF-beta signaling components correlated with upregulation of fibrosis markers
      collagen 1 and fibronectin, responses that were inhibited by administration of
      the TGF-beta receptor 1 inhibitors SB431542 or GW788388. After SMG regeneration
      following a 28 day duct deligation, TGF-beta signaling components and epithelial
      mesenchymal transition markers returned to levels similar to non-ligated
      controls. The results from this study indicate that increased TGF-beta signaling
      contributes to duct ligation-induced changes in salivary epithelium that
      correlate with glandular fibrosis. Furthermore, the reversibility of enhanced TGF
      beta signaling in acinar cells of duct-ligated mouse SMG after deligation
      indicates that this is an ideal model for studying TGF-beta signaling mechanisms
      in salivary epithelium as well as mechanisms of fibrosis initiation and their
      resolution. 

PMID- 25955536
TI  - Adlayer-mediated antibody immobilization to stainless steel for potential
      application to endothelial progenitor cell capture.
AB  - This work describes the straightforward surface modification of 316L stainless
      steel with BTS, S-(11-trichlorosilylundecanyl)-benzenethiosulfonate, a thiol
      reactive trichlorosilane cross-linker molecule designed to form intermediary
      coatings with subsequent biofunctionalization capability. The strategy is more
      specifically exemplified with the immobilization of intact antibodies and their
      Fab' fragments. Both surface derivatization steps are thoroughly characterized by
      means of X-ray photoelectron spectroscopy. The antigen binding capability of both
      types of biofunctionalized surfaces is subsequently assessed by fluorescence
      microscopy. It was determined that BTS adlayers achieve robust immobilization of
      both intact and fragmented antibodies, while preserving antigen binding activity.
      Another key finding was the observation that the Fab' fragment immobilization
      strategy would constitute a preferential option over that involving intact
      antibodies in the context of in vivo capture of endothelial progenitor cells in
      stent applications. 

PMID- 25955537
TI  - Convenience store visits by US adolescents: Rationale for healthier retail
      environments.
AB  - Given interest in the public health impact of convenience stores, it is
      surprising that so little is known about the popularity of these destinations for
      youth. We surveyed 2772 adolescents (age 13-16) from a nationally representative
      web panel of US households. Nearly half (47.5%) of adolescents reported visiting
      convenience stores at least weekly. Significant risk factors for frequent visits
      were age, being African-American, living in rural areas and in areas with higher
      levels of neighborhood deprivation. With approximately 4.1 million US adolescents
      visiting convenience stores at least weekly, new policies and other interventions
      are needed to promote a healthier retail environment for youth. 

PMID- 25955538
TI  - Transcriptional control of fungal cell cycle and cellular events by Fkh2, a
      forkhead transcription factor in an insect pathogen.
AB  - Transcriptional control of the cell cycle by forkhead (Fkh) transcription factors
      is likely associated with fungal adaptation to host and environment. Here we show
      that Fkh2, an ortholog of yeast Fkh1/2, orchestrates cell cycle and many cellular
      events of Beauveria bassiana, a filamentous fungal insect pathogen. Deletion of
      Fkh2 in B. bassiana resulted in dramatic down-regulation of the cyclin-B gene
      cluster and hence altered cell cycle (longer G2/M and S, but shorter G0/G1,
      phases) in unicellular blastospores. Consequently, DeltaFkh2 produced twice as
      many, but smaller, blastospores than wild-type under submerged conditions, and
      formed denser septa and shorter/broader cells in aberrantly branched hyphae. In
      these hyphae, clustered genes required for septation and conidiation were
      remarkedly up-regulated, followed by higher yield and slower germination of
      aerial conidia. Moreover, DeltaFkh2 displayed attenuated virulence and decreased
      tolerance to chemical and environmental stresses, accompanied with altered
      transcripts and activities of phenotype-influencing proteins or enzymes. All the
      changes in DeltaFkh2 were restored by Fkh2 complementation. All together, Fkh2
      dependent transcriptional control is vital for the adaptation of B. bassiana to
      diverse habitats of host insects and hence contributes to its biological control
      potential against arthropod pests. 

PMID- 25955540
TI  - Structural characterization of eutectic aqueous NaCl solutions under variable
      temperature and pressure conditions.
AB  - The structure of amorphous NaCl solutions produced by fast quenching is studied
      as a function of pressure, up to 4 GPa, by combined neutron diffraction
      experiments and classical molecular dynamics simulations. Similarly to LiCl
      solutions the system amorphizes at ambient pressure in a dense phase structurally
      similar to the e-HDA phase in pure water. The measurement of the static structure
      factor as a function of pressure allowed us to validate a new polarizable force
      field developed by Tazi et al., 2012, never tested under non-ambient conditions.
      We infer from simulations that the hydration shells of Na(+) cations form well
      defined octahedra composed of both H2O molecules and Cl(-) anions at low
      pressure. These octahedra are gradually broken by the seventh neighbour moving
      into the shell of first neighbours yielding an irregular geometry. In contrast to
      LiCl solutions and pure water, the system does not show a polyamorphic transition
      under pressure. This confirms that the existence of polyamorphism relies on the
      tetrahedral structure of water molecules, which is broken here. 

PMID- 25955539
TI  - Overexpression of lymphoid enhancer-binding factor-1 (LEF1) is a novel favorable
      prognostic factor in childhood acute lymphoblastic leukemia.
AB  - INTRODUCTION: Lymphoid enhancer-binding factor-1 (LEF1) is a target gene and
      central mediator of the Wnt signaling pathway. High LEF1 expression has been
      reported as a prognostic marker in several types of hematologic malignancies of
      adult patients. METHODS: In this study, LEF1 expression was analyzed by real-time
      polymerase chain reaction (PCR) in 122 children with newly diagnosed ALL treated
      on the China NPCAC97 protocols. Patients' samples were dichotomized at the median
      value of control group and divided into LEF1(low) and LEF1(high) groups. RESULTS:
      The LEF1 mRNA levels in patients with ALL were significantly higher than those of
      normal controls, and the LEF1 levels were dramatically decreased following
      induction therapy. In addition, LEF1(high) patients had lower white blood cell
      (WBC) count at diagnosis and lower minimal residual disease (MRD) levels at the
      time of complete remission as compared to LEF1(low) patients. Finally, our
      studies showed that high LEF1 expression is associated with favorable CR rate and
      overall survival (OS) in childhood ALL (5-year OS: LEF1(high) 92% vs. LEF1(low)
      73%, P = 0.009). High LEF1 level was associated with a favorable relapse-free
      survival in standard-risk patients and also related to a better OS within the
      subgroup of patients with BCR-ABL-negative ALL. CONCLUSION: Overexpression of
      LEF1 is a favorable prognostic factor in childhood ALL. The prognostic impact of
      LEF1 may assist treatment stratification and suggest the need of alternative
      regimens.

PMID- 25955535
TI  - Language outcomes among ELBW infants in early childhood.
AB  - BACKGROUND: Limited data are available evaluating language outcomes of preterm
      infants in early childhood. Furthermore, the relationship between language
      outcomes, medical morbidities and developmental trajectory in early infancy is
      unclear. AIMS: The goal of this study was to evaluate language outcomes among
      extremely low birth weight (ELBW) infants at 30months adjusted age (AA). STUDY
      DESIGN: The Bayley Scales of Infant Development II and the Peabody Picture
      Vocabulary Test or Expressive One Word Picture Vocabulary Test/Receptive One Word
      Picture Vocabulary Test were administered at 30months AA to a prospective cohort
      of ELBW infants who participated in the NICHD Neonatal Network Glutamine Trial
      and Neurodevelopmental Follow-Up Study. A standardized history and physical
      examination and query regarding feeding behaviors were performed at 18months AA
      and 30months AA. RESULTS: Of the 467 infants evaluated, 55% had receptive
      language delay at 30months with 23% having severe delays. Fewer (26%) had
      expressive language delays, with 16% of those being severe delays. Non-English
      speaking infants had poorer performance on all language measures compared to
      English-speaking infants. Forty-seven percent of the cohort required assistance
      with feeds at 18months. These children were more likely to have language delay at
      the 30month assessment compared to infants who could feed themselves.
      CONCLUSIONS: ELBW infants are at risk of language delay in early childhood.
      Additional research is needed to further explore the relationship between early
      predictors of language delay and the use of monolingual language assessments in
      non-English speaking patients with a history of prematurity.

PMID- 25955541
TI  - Healthy Canada by Design. Introduction.

PMID- 25955542
TI  - The unmet demand for walkability: Disparities between preferences and actual
      choices for residential environments in Toronto and Vancouver.
AB  - OBJECTIVES: Individual preferences for residential location, neighbourhood
      character and travel options are not always met. The availability and cost of
      housing and several other factors often require compromise. The primary
      objectives of this study were to examine neighbourhood preferences, quantify
      unmet demand for more walkable environments and explore associations between the
      built environment, travel behaviour and health after controlling for
      neighbourhood preference. METHODS: A web-based, visually oriented residential
      preference survey was conducted with 1,525 adults in the Greater Toronto Area and
      1,223 adults in Metro Vancouver aged 25 and older (5.8% and 11.8% of total
      potential recruits, respectively). Participants were randomly selected from a pre
      recruited panel across a range of objectively calculated walkability and income
      levels at the forward sortation area level. RESULTS: Depending on the
      neighbourhood design attribute, between 45% and 64% of residents in the cities of
      Toronto and Vancouver strongly preferred living in walkable settings, compared
      with between 6% and 15% who strongly preferred auto-oriented places. Of
      participants who perceived their current neighbourhood as very auto-oriented,
      between 11% and 20% of City of Toronto participants and 6% and 30% of City of
      Vancouver participants strongly preferred a very walkable neighbourhood.
      Residents of highly walkable neighbourhoods reported walking significantly more
      for utilitarian purposes, taking public transit more frequently and driving fewer
      kilometres. CONCLUSION: Strong preferences for walking and transit-supportive
      neighbourhoods exist in two of Canada's largest metropolitan regions, with
      considerable unmet demand observed for such environments. The findings provide
      evidence for policies that enable walkability and inform market analysis,
      planning and regulatory approaches that better align with the supply and demand
      of more walkable neighbourhood environments. Providing increased opportunities
      for active transportation can have positive impacts on health-enhancing
      behaviours.

PMID- 25955545
TI  - Healthy Canada by Design: Translating science into action and prevention.

PMID- 25955544
TI  - Application of an evidence-based tool to evaluate health impacts of changes to
      the built environment.
AB  - OBJECTIVES: To create and apply an empirically based health and greenhouse gas
      (GHG) impact assessment tool linking detailed measures of walkability and
      regional accessibility with travel, physical activity, health indicators and GHG
      emissions. METHODS: Parcel land use and transportation system characteristics
      were calculated within a kilometre network buffer around each Toronto postal
      code. Built environment measures were linked with health and demographic
      characteristics from the Canadian Community Health Survey and travel behaviour
      from the Transportation Tomorrow Survey. Results were incorporated into an
      existing software tool and used to predict health-related indicators and GHG
      emissions for the Toronto West Don Lands Redevelopment. RESULTS: Walkability,
      regional accessibility, sidewalks, bike facilities and recreation facility access
      were positively associated with physical activity and negatively related to body
      weight, high blood pressure and transportation impacts. When applied to the West
      Don Lands, the software tool predicted a substantial shift from automobile use to
      walking, biking and transit. Walking and biking trips more than doubled, and
      transit trips increased by one third. Per capita automobile trips decreased by
      half, and vehicle kilometres travelled and GHG emissions decreased by 15% and
      29%, respectively. CONCLUSION: The results presented are novel and among the
      first to link health outcomes with detailed built environment features in Canada.
      The resulting tool is the first of its kind in Canada. This tool can help policy
      makers, land use and transportation planners, and health practitioners to
      evaluate built environment influences on health-related indicators and GHG
      emissions resulting from contrasting land use and transportation policies and
      actions.

PMID- 25955543
TI  - Grassroots projects aimed at the built environment: Association with
      neighbourhood deprivation, land-use mix and injury risk to road users.
AB  - OBJECTIVES: 1) To describe grassroots projects aimed at the built environment and
      associated with active transportation on the Island of Montreal; and 2) to
      examine associations between the number of projects and indicators of
      neighbourhood material and social deprivation and the built environment. METHOD:
      We identified funding agencies and community groups conducting projects on built
      environments throughout the Island of Montreal. Through website consultation and
      a snowballing procedure, we inventoried projects that aimed at transforming built
      environments and that were carried out by community organizations between January
      1, 2006, and November 1, 2010. We coded and validated information about project
      activities and created an interactive map using Geoclip software. Correlational
      analyses quantified associations between number of projects, neighbourhood
      characteristics and deprivation. RESULTS: A total of 134 community organizations
      were identified, and 183 grassroots projects were inventoried. A large number of
      projects were aimed at increasing awareness of/improving active or public
      transportation (n=95), improving road safety (n=84) and enhancing neighbourhood
      beautification and greening (n=69). The correlation between the presence of
      projects and the extent of neighbourhood material deprivation was small
      (Kendall's t=0.26, p<0.001), but in areas with greater social deprivation there
      were more projects (Kendall's t=0.38, p<0.001). Larger numbers of projects were
      also associated with the presence of more extensive land-use mix (Kendall's
      t=0.23, p<0.001) and a greater proportion of road intersections with injured
      pedestrians, cyclists and motor vehicle users (Kendall's t=0.43, p<0.001).
      CONCLUSION: There is significant community mobilization around built environments
      and active transportation. Investigations of the implementation processes and
      impacts are warranted.

PMID- 25955546
TI  - Incorporating consideration of health impacts into land use development approval
      processes: Development of a Health Background Study Framework.
AB  - OBJECTIVES: This project involved development of a Health Background Study (HBS)
      Framework to support consideration of health impacts within municipalities'
      approval process for land use development. PARTICIPANTS: Peel Public Health and
      Toronto Public Health led the project with the participation of planners, urban
      designers, engineers, public health staff and development industry
      representatives. SETTING: Historical growth in the Region of Peel and suburban
      Toronto has resulted in extensive low-density development, creating car-dependent
      communities with disconnected streets and segregated land uses. INTERVENTION: The
      inclusion of an HBS in developers' applications to municipalities is one approach
      by which health-related expectations for the built environment can be established
      within the approval process. Development of the HBS Framework used the six core
      elements of the built environment with the strongest evidence for impact on
      health and was informed by analysis of the provincial and local policy contexts,
      practices of other municipalities and stakeholder interviews. The Framework's
      contents were refined according to feedback from multidisciplinary stakeholder
      workshops. OUTCOMES: The HBS Framework identifies minimum standards for built
      environment core elements that developers need to address in their applications.
      The Framework was created to be simple and instructive with applicability to a
      range of development locations and scales, and to various stages of the
      development approval process. Peel Public Health is leading several initiatives
      to support the use of the HBS as a part of the development application process.
      CONCLUSION: The HBS Framework is a tool that public health and planning can use
      to support the consideration of health impacts within municipalities' land use
      development processes.

PMID- 25955547
TI  - Building the capacity of health authorities to influence land use and
      transportation planning: Lessons learned from the Healthy Canada by Design CLASP
      Project in British Columbia.
AB  - OBJECTIVES: The main objective of the Healthy Canada by Design CLASP Initiative
      in British Columbia (BC) was to develop, implement and evaluate a capacity
      building project for health authorities. The desired outcomes of the project were
      as follows: 1) increased capacity of the participating health authorities to
      productively engage in land use and transportation planning processes; 2) new and
      sustained relationships or collaborations among the participating health
      authorities and among health authorities, local governments and other built
      environment stakeholders; and 3) indication of health authority influence and/or
      application of health evidence and tools in land use and transportation plans and
      policies. PARTICIPANTS: This project was designed to enhance the capacity of
      three regional health authorities, namely Fraser Health, Island Health and
      Vancouver Coastal Health, and their staff. These were considered the project's
      participants. SETTINGS: The BC regions served by the three health authorities
      cover the urban, suburban and rural spectrum across relatively large and diverse
      geographic areas. The populations have broad ranges in socio-economic status,
      demographic profiles and cultural and political backgrounds. INTERVENTION: The
      Initiative provided the three health authorities with a consultant who had
      several years of experience working on land use and transportation planning. The
      consultant conducted situational assessments to understand the baseline knowledge
      and skill gaps, assets and objectives for built environment work for each of the
      participating health authorities. On the basis of this information, the
      consultant developed customized capacity-building work plans for each of the
      health authorities and assisted them with implementation. Capacity-building
      activities were as follows: researching health and built environment strategies,
      policies and evidence; transferring health evidence and promising policies and
      practices from other jurisdictions to local planning contexts; providing training
      and support with regard to health and the built environment to health authority
      staff; bringing together public health staff with local planners for networking;
      and participating in land use planning processes. OUTCOMES: The project helped to
      expand the capacity of participating health authorities to influence land use and
      transportation planning decisions by increasing the content and process expertise
      of public health staff. The project informed structural changes within health
      authorities, such as staffing reallocations to advance built environment work
      after the project. Health authorities also forged new relationships within and
      across sectors, which facilitated knowledge exchange and access of the public
      health sector to opportunities to influence built environment decisions. By the
      end of the project, there was emerging evidence of a health presence in land use
      policy documents. CONCLUSIONS: The project helped to prioritize, accelerate and
      formalize the participating health authorities' involvement in land use and
      transportation planning processes. In the long term, this is expected to lead to
      health policies and programs that consider the built environment, and to built
      environment policies and practices that integrate population health goals,
      thereby reducing the risk of chronic diseases.

PMID- 25955548
TI  - Healthy Toronto by Design: Promoting a healthier built environment.
AB  - Chronic diseases, obesity and sedentary lifestyles are some of the health
      challenges facing Canada today. There is increasing recognition and evidence that
      the way our cities are planned, designed and built can contribute to these
      problems. Many of the policy levers to address the built environment exist
      outside the health sector and at the municipal level in areas such as urban
      planning, transportation, parks and recreation, and housing. The challenge for
      the public health sector is to build and sustain partnerships and collaboration
      across various sectors to ensure that health is considered in built environment
      policies. As the public health unit for the city of Toronto and part of the
      municipal government, Toronto Public Health is in a unique position to provide
      leadership, advocacy and support for healthy municipal public policies related to
      the built environment. This article provides some examples of CLASP (Coalitions
      Linking Action and Science for Prevention) initiatives undertaken to help create
      support for healthy public policies in the built environment and suggests that
      the "Healthy Cities" approach is a useful framework to promote policy change in
      the built environment at the municipal level. 

PMID- 25955549
TI  - Healthy Canada by Design CLASP: Lessons learned from the first phase of an
      intersectoral, cross-provincial, built environment initiative.
AB  - OBJECTIVES: The Healthy Canada by Design (HCBD) CLASP (Coalitions Linking Action
      and Science for Prevention) Initiative promotes the building of communities that
      support health by 1) facilitating the integration of health evidence into built
      environment decision-making; 2) developing new, cross-sector collaboration models
      and tools; and 3) fostering a national community of practice. PARTICIPANTS: A
      coalition of public health professionals, researchers, professional planners and
      non-governmental organization (NGO) staff from across Canada developed,
      implemented and participated in the Initiative. SETTINGS: In the first phase,
      HCBD interventions took place for the most part in large urban and suburban
      settings in Quebec, Ontario and British Columbia. National knowledge transfer and
      exchange (KTE) activities were delivered both locally and nationally.
      INTERVENTION: Project participants developed tools or processes for collaboration
      between the health and the community planning sectors. These were designed to
      increase the capacity of the health sector to influence decisions about land use
      and transportation planning. Tool or process development was accompanied by pilot
      testing, evaluation, and dissemination of findings and lessons learned. On a
      parallel track, NGOs involved with HCBD led national KTE interventions. OUTCOMES:
      The first phase of HCBD demonstrated the potential for public health
      organizations to influence the built environment determinants of cancer and
      chronic diseases. Public health authorities forged relationships with several
      organizations with a stake in built environment decisions, including municipal
      and regional planning departments, provincial governments, federal government
      agencies, researchers, community groups and NGOs. The Initiative accomplished the
      following: 1) created new relationships across sectors and across health
      authorities; 2) improved the knowledge and skills for influencing land use
      planning processes among public health professionals; 3) increased awareness of
      health evidence and intent to change practice among built environment decision
      makers; and 4) facilitated inclusion of health considerations in local plans,
      policies and decisions. CONCLUSIONS: The first phase of HCBD engaged built
      environment stakeholders, including public health professionals, planners,
      researchers, community groups and NGOs, in ways that would be expected to
      influence health risk factors and population health outcomes in the long term.

PMID- 25955550
TI  - Building a community of practice: Healthy Canada by Design CLASP Renewal-
      Postscript.

PMID- 25955551
TI  - Influencing public policies: Two (very good) reasons to look toward scientific
      knowledge in public policy.
AB  - The healthy public policy movement rests on the belief that a range of public
      policies should be at least partly informed by evidence demonstrating the
      positive effects of these policies on population health, health inequalities and
      their determinants. In order to address certain difficulties that the movement
      faces, knowledge produced in various scientific disciplines regarding public
      policies may provide some valuable guidance. In this short commentary, we examine
      how knowledge from the scientific disciplines investigating public policies makes
      it possible to address two difficulties in the development of healthy public
      policies: 1) adequately anticipating the effects of public policies, and 2)
      assessing the political viability of the policies being promoted. Since urban
      traffic policies are of interest to most of the other contributors to this
      supplement, we use examples from this field to illustrate some of our points.

PMID- 25955553
TI  - Children with disabilities in child protection services.

PMID- 25955554
TI  - Novel Detection of Insecticide Resistance Related P450 Genes and Transcriptome
      Analysis of the Hemimetabolous Pest Erthesina fullo (Thunberg) (Hemiptera:
      Heteroptera).
AB  - Erthesina fullo (Thunberg, 1783) is an economically important heteropteran
      species in China. Since only three nucleotide sequences of this species (COI, 16S
      rRNA, and 18S rRNA) appear in the GenBank database so far, no analysis of the
      molecular mechanisms underlying E. fullo's resistance to insecticide and
      environmental stress has been accomplished. We reported a de novo assembled and
      annotated transcriptome for adult E. fullo using the Illumina sequence system. A
      total of 53,359,458 clean reads of 4.8 billion nucleotides (nt) were assembled
      into 27,488 unigenes with an average length of 750 bp, of which 17,743 (64.55%)
      were annotated. In the present study, we identified 88 putative cytochrome P450
      sequences and analyzed the evolution of cytochrome P450 superfamilies, genes of
      the CYP3 clan related to metabolizing xenobiotics and plant natural compounds, in
      E. fullo, increasing the candidate genes for the molecular mechanisms of
      insecticide resistance in P450. The sequenced transcriptome greatly expands the
      available genomic information and could allow a better understanding of the
      mechanisms of insecticide resistance at the systems biology level. 

PMID- 25955555
TI  - Association of the ACE I/D gene polymorphisms with JAK2V617F-positive
      polycythemia vera and essential thrombocythemia.
AB  - The renin-angiotensin system contributes to cell growth, proliferation, and
      differentiation in the bone marrow. We investigated the role of the ACE I/D gene
      polymorphism in 108 polycythemia vera (PV) and essential thrombocytosis (ET)
      patients who were positive for the JAK2V617F mutation, with a thrombosis group
      (TG) of 95 patients who had a history of vascular events, but did not have a
      history of myeloproliferative neoplasms and compared these to a healthy control
      group (CG) of 72 subjects. In the patients, II genotype and I allele frequency
      (p=0.009, odds ratio [OR]=9.716, 95% confidence interval [CI]=1.242-76.00,
      p=0.004, OR=2.019, 95% CI=1.243-3.280, respectively) were found to be higher than
      those in the controls. The DD genotype (p=0.021, OR=0.491, 95% CI=0.268-0.899)
      and D allele (p=0.004, OR=0.495, 95% CI=0.305-0.805) were found to be correlated
      with a decreased risk of a myeloproliferative neoplasm. These findings support
      the hypothesis that the ACE II genotype and I allele may be related to increased
      risk of ET and PV. Conversely, the DD genotype and D allele may be related to
      decreased risk of ET and PV. The results also indicated that the ACE I/D gene
      polymorphism was independent of thrombosis formation.

PMID- 25955556
TI  - Age-specific incidence, risk factors and outcome of acute abdominal aortic
      aneurysms in a defined population.
AB  - BACKGROUND: Contemporary population-based data on age-specific incidence and
      outcome from acute abdominal aortic aneurysm (AAA) events are needed to
      understand the impact of risk factor modification and demographic change, and to
      inform AAA screening policy. METHODS: In a prospective population-based study
      (Oxfordshire, UK, 2002-2014), event rates, incidence, early case fatality and
      long-term outcome from all acute AAA events were determined, both overall and in
      relation to the four main risk factors: smoking, hypertension, male sex and age.
      RESULTS: Over the 12-year interval, 103 incident acute AAA events occurred in the
      study population of 92,728 (men 72.8 per cent; 59.2 per cent 30-day case fatality
      rate). The incidence per 100,000 population per year was 55 in men aged 65-74
      years, but increased to 112 at age 75-84 years and to 298 at age 85 years or
      above. Some 66.0 per cent of all events occurred in those aged 75 years or more.
      The incidence at 65-74 years was highest in male smokers (274 per 100,000
      population per year); 27 (96 per cent) of 28 events in men aged less than 75
      years occurred in ever-smokers. Mean(s.d.) age at event was lowest in current
      smokers (72.2(7.2) years), compared with that in ex-smokers (81.2(7.0) years) and
      never-smokers (83.3(7.9) years) (P < 0.001). Hypertension was the predominant
      risk factor in women (diagnosed in 93 per cent), with 20 (71 per cent) of all 28
      events in women occurring in those aged 75 years or above with hypertension. The
      30-day case fatality rate increased from 40 per cent at age below 75 years to 69
      per cent at age 75 years or more (P = 0.008). CONCLUSION: Two-thirds of acute AAA
      events occurred at age 75 years or above, and more than 25 per cent of events
      were in women. Taken with the strong associations with smoking and hypertension,
      these findings could have implications for AAA screening.

PMID- 25955557
TI  - Analysis of Cynandione A's Anti-Ischemic Stroke Effects from Pathways and Protein
      Protein Interactome.
AB  - Ischemic stroke is the third leading cause of death in the world. Our previous
      study found that cynandione A (CYNA), the main component from the root of
      Cynanchum bungei, exhibits anti-ischemic stroke activity. In this work, we
      investigated the therapeutic mechanisms of CYNA to ischemic stroke at protein
      network level. First, PC12 cells and cerebellar granule neurons were prepared to
      validate the effects of CYNA against glutamate injury. Our experiments suggested
      that CYNA could dose-dependently mitigate glutamate-induced neurons neurotoxicity
      and inhibit glutamate-induced upregulation of KHSRP and HMGB1, further confirming
      the neuroprotective effects of CYNA in vivo. Then, on the pathway sub-networks,
      which present biological processes that can be impacted directly or in periphery
      nodes by drugs via their targets, we found that CYNA regulates 11 pathways
      associated with the biological process of thrombotic or embolic occlusion of a
      cerebral artery. Meanwhile, by defining a network-based anti-ischemic stroke
      effect score, we showed that CYNA has a significantly higher effect score than
      random counterparts, which suggests a synergistic effect of CYNA to ischemic
      stroke. This study may shed new lights on the study of network based
      pharmacology. 

PMID- 25955558
TI  - Derivation of inter-lamellar behaviour of the intervertebral disc annulus.
AB  - The inter-lamellar connectivity of the annulus fibrosus in the intervertebral
      disc has been shown to affect the prediction of the overall disc behaviour in
      computational models. Using a combined experimental and computational approach,
      the inter-lamellar mechanical behaviour of the disc annulus was investigated
      under conditions of radial loading. Twenty-seven specimens of anterior annulus
      fibrosus were dissected from 12 discs taken from four frozen ovine thoracolumbar
      spines. Specimens were grouped depending on their radial provenance within the
      annulus fibrosus. Standard tensile tests were performed. In addition, micro
      tensile tests under microscopy were used to observe the displacement of the
      lamellae and inter-lamellar connections. Finite elements models matching the
      experimental protocols were developed with specimen-specific geometries and
      boundary conditions assuming a known lamellar behaviour. An optimisation process
      was used to derive the interface stiffness values for each group. The assumption
      of a linear cohesive interface was used to model the behaviour of the inter
      lamellar connectivity. The interface stiffness values derived from the
      optimisation process were consistently higher than the corresponding lamellar
      values. The interface stiffness values of the outer annulus were from 43% to 75%
      higher than those of the inner annulus. Tangential stiffness values for the
      interface were from 6% to 39% higher than normal stiffness values within each
      group and similar to values reported by other investigators. These results
      reflect the intricate fibrous nature of the inter-lamellar connectivity and
      provide values for the representation of the inter-lamellar behaviour at a
      continuum level. 

PMID- 25955559
TI  - Air-puff associated quantification of non-linear biomechanical properties of the
      human cornea in vivo.
AB  - With the advent of newer techniques to correct refraction such as flapless laser
      procedure and collagen crosslinking, in vivo estimation of corneal biomechanical
      properties has gained importance. In this study, a new 3-D patient specific
      inverse finite element method of estimating corneal biomechanical properties from
      air-puff applanation was developed. The highlight of the model was inclusion of
      patient-specific corneal tomography, fiber dependent hyperelastic model, cross
      links between collagen lamellae and epithelium layer. A lumped mass, spring and
      dashpot model was included to model the resistance to motion and deformation of
      the eye globe caused by air-puff applanation. 10 normal eyes of 10 human subjects
      were used for the study. 3-D finite element models were constructed and custom
      routines were scripted for performing the inverse calculations. The model for
      each eye was perturbed to estimate the effect of measured intraocular pressure on
      the estimated biomechanical variables. The study demonstrated that the inverse
      method was effective in quantification of material properties and was sensitive
      to intraocular pressure alterations. Specifically, in vivo fiber dependent
      hyperelastic biomechanical properties of human corneas were estimated for the
      first time. 

PMID- 25955560
TI  - Biocompatibility and compressive properties of Ti-6Al-4V scaffolds having Mg
      element.
AB  - Porous scaffolds of Ti-6Al-4V were produced by mixing of this alloy with
      different amount of magnesium (Mg) powders. The mixtures were compacted in steel
      die by applying uniaxial pressure of 500 MPa before sintering the compacts in
      sealed quartz tubes at 900  degrees C for 2 h. Employing Archimedes' principle
      and Image Tool software, the total and open volume percentages of porosities
      within the scaffolds were found to be in the range of 47-64% and 41-47%,
      respectively. XRD results of titanium before and after sintering showed that no
      contamination, neither oxides nor nitrides formed during processes. Compressive
      properties of the scaffolds were studied using an Instron machine. The observed
      compressive strength and Young's module of the scaffolds were in the range of 72
      132 MPa, and 37-47 GPa, respectively. Cell attachment and proliferation rate of
      MG-63 on porous samples were investigated. The results showed that proliferation
      rate increased with increasing Mg content. However no clear differences were
      observed between samples regarding cell attachment, so that bridges were observed
      in all cell gaps within the scaffolds.

PMID- 25955561
TI  - Fiber-matrix integrity, micromorphology and flexural strength of glass fiber
      posts: Evaluation of the impact of rotary instruments.
AB  - Several rotary instruments have been daily employed on clinic to promote cut
      aiming to adjust the length of fiber posts to the radicular conduct, but there is
      no information on the literature about the effects of the different rotary
      instruments and its impact on the micromorphology of surface and mechanical
      properties of the glass fiber post. This study aimed the impact of rotary
      instruments upon fiber-matrix integrity, micromorphology and flexural-strength of
      glass-fiber posts (GFP). GFP (N=110) were divided into 5 groups: Ctrl: as
      received posts, DBc: coarse diamond-bur, DBff: extra-fine diamond-bur, CB:
      carbide-bur, DD: diamond-disc. Cutting procedures were performed under abundant
      irrigation. Posts exposed to rotary instruments were then subjected to 2-point
      inclined loading test (compression 45 degrees ) (n=10/group) and 3-point flexural
      strength test (n=10/group). Fiber-matrix integrity and micromorphology at the cut
      surface were analyzed using a SEM (n=2/group). Cutting procedures did not
      significantly affect the 2-point (51.7+/-4.3-56.7+/-5.1 MPa) (p=0.0233) and 3
      point flexural-strength (671.5+/-35.3-709.1+/-33.1 MPa) (p=0.0968) of the posts
      (One-way ANOVA and Tukey's test). Fiber detachment was observed only at the end
      point of the cut at the margins of the post. Cut surfaces of the CB group were
      smoother than those of the other groups. After 3-point flexural strength test,
      fiber-matrix separation was evident at the tensile side of the post. Rotary
      instruments tested with simultaneous water-cooling did not affect the resistance
      of the tested fiber posts but caused disintegration of the fibers from the matrix
      at the end of the cut, located at the margins.

PMID- 25955562
TI  - Analysis of toughening mechanisms in the Strombus gigas shell.
AB  - A finite element analysis of the fracture mechanisms in the Strombus gigas conch
      shell is presented in this work. The S. gigas shell has a complex
      microarchitecture that consists of three main macroscopic layers of calcium
      carbonate: the inner, middle, and outer layers. Each layer is composed of
      lamellae of calcium carbonate, held together by a cohesive organic protein. As a
      result of this elaborate architecture, the S. gigas shell exhibits a much greater
      damage tolerance than the calcium carbonate by itself, with a work of fracture
      reported to be three magnitudes of order greater. The two main energy dissipating
      factors that contribute to this are multiple, parallel cracking along first-order
      interfaces in the inner and outer layers and crack bridging through the second
      order interfaces of the middle layer. Finite element analysis was conducted to
      simulate and replicate flexural strength and work-of-fracture results obtained in
      the literature for both dry and wet physical bend test specimens. Several
      parameters were varied including protein strength and fracture toughness, initial
      protein damage, and the relative heights of macroscopic layers in order to create
      a model that predicted published, experimental results. The simulations indicate
      that having some initially weakened protein interfaces is key to matching the
      parallel cracking in the inner layer of the physical specimens. The wet models
      exhibit significantly higher work of fracture compared to the dry specimens in
      large part due to a crack growth resistance behavior in the middle layer, which
      was successfully modeled. The parametric studies that have been performed on the
      finite element models provide guidelines for manufacturing the ideal S. gigas
      inspired, biomimetic composite. 

PMID- 25955563
TI  - Quantification of nonlinear elasticity for the evaluation of submillimeter crack
      length in cortical bone.
AB  - The objective of this study was to investigate the sensitivity of the nonlinear
      elastic properties of cortical bone to the presence of a single submillimetric
      crack. Nonlinear elasticity was measured by nonlinear resonant ultrasound
      spectroscopy (NRUS) in 14 human cortical bone specimens. The specimens were
      parallelepiped beams (50*2*2 mm(3)). A central notch of 500 um was made to
      control crack initiation and propagation during four-point bending. The nonlinear
      hysteretic elastic and dissipative parameters alphaf and alphaQ, and Young's
      modulus Eus were measured in dry condition for undamaged (control) specimens and
      in dry and wet conditions for damaged specimens. The length of the crack was
      assessed using synchrotron radiation micro-computed tomography (SR-MUCT) with a
      voxel size of 1.4 MUm. The initial values of alphaf, measured on the intact
      specimens, were remarkably similar for all the specimens (alphaf =-5.5+/-1.5).
      After crack propagation, the nonlinear elastic coefficient alphaf increased
      significantly (p<0.006), with values ranging from -4.0 to -296.7. Conversely, no
      significant variation was observed for alphaQ and Eus. A more pronounced
      nonlinear elastic behavior was observed in hydrated specimens compared to dry
      specimens (p<0.001) after propagation of a single submillimetric crack. The
      nonlinear elastic parameter alphaf was found to be significantly correlated to
      the crack length both in dry (R=0.79, p<0.01) and wet (R=0.84, p<0.005)
      conditions. Altogether these results show that nonlinear elasticity assessed by
      NRUS is sensitive to a single submillimetric crack induced mechanically and
      suggest that the humidity must be strictly controlled during measurements.

PMID- 25955564
TI  - Responsiveness of the Spanish Pelvic Floor Distress Inventory and Pelvic Floor
      Impact Questionnaires Short Forms (PFDI-20 and PFIQ-7) in women with pelvic floor
      disorders.
AB  - OBJECTIVE: To evaluate the responsiveness of the Spanish versions of Pelvic Floor
      Distress Inventory and Pelvic Floor Impact Questionnaire Short Forms (PFDI-20 and
      PFIQ-7), in order to assess symptoms and quality of life in Spanish women with
      pelvic floor disorders. STUDY DESIGN: Prospective observational study to assess
      the responsiveness in 85 women with pelvic floor disorders. PFDI-20 and PFIQ-7
      were completed before and after Physiotherapy intervention. The responsiveness
      was assessed with the p values using the Wilcoxon signed-rank test, the
      standardized response means of the change (SRM) and the effect size (ES).
      RESULTS: The Spanish PFDI-20 and PFIQ-7 and the subscales demonstrated small to
      good responsiveness. The responsiveness was higher for PFDI-20 than for PFIQ-7.
      The statistic for PFDI-20 was moderate to good (ES 0.68 and SRM 0.84; p<0.0001),
      and small to moderate for PFIQ-7 (ES 0.48 and SRM 0.57; p<0.0001). Regarding the
      subscales, the responsiveness was better for Pelvic Organ Prolapse Distress
      Inventory (POPDI) than Pelvic Organ Prolapse Impact Questionnaire (POPIQ) (ES
      0.70 and SRM 0.78; ES 0.42 and SRM 0.47 respectively; p<0.0001). Moderate
      responsiveness was found for Urinary Distress Inventory (UDI) and Urinary Impact
      Questionnaire (UIQ) (ES 0.54 and SRM 0.67; ES 0.52 and SRM 0.61 respectively;
      p<0.0001). Colo-Rectal-Anal Distress Inventory (CRADI) and Colo-Rectal-Anal
      Impact Questionnaire (CRAIQ) showed poor responsiveness, small in both (ES 0.42,
      SRM 0.50 and p<0.0001; ES 0.34, SRM 0.39 respectively; p<0.001). All
      responsiveness was significant. CONCLUSIONS: PFDI-20 and PFIQ-7 Spanish versions
      showed good responsiveness to evaluate the symptoms and the quality of life in
      Spanish women with PFD undergoing Physiotherapy treatment.

PMID- 25955566
TI  - Dual-Responsive pH and Temperature Sensitive Nanoparticles Based on Methacrylic
      Acid and Di(ethylene glycol) Methyl Ether Methacrylate for the Triggered Release
      of Drugs.
AB  - A series of thermo-and pH-responsive poly(methyl methacrylate)-block
      poly[methacrylic acid-co-di(ethylene glycol) methyl ether methacrylate] PMMA-b
      P[MAA-co-DEGMA] block copolymers were synthesized by RAFT polymerization and self
      assembled into micelles. The molar ratio of MAA was altered from 0-12% in order
      to modulate the lower critical solution temperature (LCST) of PDEGMA. The release
      of the drug albendazole from the micelle was strongly dependent on the
      temperature and the LCST value of the polymer. Systems below the LCST released
      the drug slowly while increasing the temperature above the LCST or decreasing the
      pH value to 5 resulted in the burst-like release of the drug. ABZ delivered in
      this pH-responsive drug carrier had a higher toxicity than the free drug or the
      drug delivered in a non-responsive drug carrier. 

PMID- 25955565
TI  - Post-transcriptional inactivation of matrix metalloproteinase-12 after focal
      cerebral ischemia attenuates brain damage.
AB  - This study highlights the possible pathological role of MMP-12 in the context of
      ischemic stroke. Male rats were subjected to a two-hour middle cerebral artery
      occlusion (MCAO) procedure. MMP-12 shRNA expressing plasmid formulation was
      administered to these rats twenty-four hours after reperfusion. The results
      showed a predominant upregulation of MMP-12 (approximately 47, 58, 143, and 265
      folds on days 1, 3, 5, 7 post-ischemia, respectively) in MCAO subjected rats. MMP
      12 expression was localized to neurons, oligodendrocytes and microglia, but not
      astrocytes. Transcriptional inactivation of MMP-12 significantly reduced the
      infarct size. The percent infarct size was reduced from 62.87+/-4.13 to 34.67+/
      5.39 after MMP-12 knockdown compared to untreated MCAO subjected rats. Expression
      of myelin basic protein was increased, and activity of MMP-9 was reduced in
      ischemic rat brains after MMP-12 knockdown. Furthermore, a significant reduction
      in the extent of apoptosis was noticed after MMP-12 knockdown. TNFalpha
      expression in the ipsilateral regions of MCAO-subjected rats was reduced after
      MMP-12 knockdown in addition to the reduced protein expression of apoptotic
      molecules that are downstream to TNFalpha signaling. Specific knockdown of MMP-12
      after focal cerebral ischemia offers neuroprotection that could be mediated via
      reduced MMP-9 activation and myelin degradation as well as inhibition of
      apoptosis.

PMID- 25955567
TI  - High prevalence of cardiovascular disease in South Asians: Central role for brown
      adipose tissue?
AB  - Cardiovascular disease (CVD) is the leading cause of death in modern society.
      Interestingly, the risk of developing CVD varies between different ethnic groups.
      A particularly high risk is faced by South Asians, representing over one-fifth of
      the world's population. Here, we review potential factors contributing to the
      increased cardiovascular risk in the South Asian population and discuss novel
      therapeutic strategies based on recent insights. In South Asians, classical
      ('metabolic') risk factors associated with CVD are highly prevalent and include
      central obesity, insulin resistance, type 2 diabetes, and dyslipidemia. A
      contributing factor that may underlie the development of this disadvantageous
      metabolic phenotype is the presence of a lower amount of brown adipose tissue
      (BAT) in South Asian subjects, resulting in lower energy expenditure and lower
      lipid oxidation and glucose uptake. As it has been established that the increased
      prevalence of classical risk factors in South Asians cannot fully explain their
      increased risk for CVD, other non-classical risk factors must underlie this
      residual risk. In South Asians, the prevalence of "inflammatory" risk factors
      including visceral adipose tissue inflammation, endothelial dysfunction, and HDL
      dysfunction are higher compared with Caucasians. We conclude that a potential
      novel therapy to lower CVD risk in the South Asian population is to enhance BAT
      volume or its activity in order to diminish classical risk factors. Furthermore,
      anti-inflammatory therapy may lower non-classical risk factors in this population
      and the combination of both strategies may be especially effective. 

PMID- 25955569
TI  - Concentrative nucleoside transporter 3 as a prognostic indicator for favorable
      outcome of t(8;21)-positive acute myeloid leukemia patients after cytarabine
      based chemotherapy.
AB  - Although acute myeloid leukemia (AML) exhibits diverse responses to chemotherapy,
      patients harboring the t(8;21) translocation are part of a favorable risk group.
      However, the reason why this subgroup is more responsive to cytarabine-based
      therapy has not been elucidated. In the present study, we analyzed expression
      levels of cytarabine metabolism-related genes in patients diagnosed with AML with
      or without t(8;21) and investigated their correlation with clinical outcomes
      after cytarabine-based therapy. Among the 8 genes studied, expression of the
      concentrative nucleoside transporter 3 (CNT3) gene was significantly higher in
      t(8;21)-positive patients compared to the others in the test population and the
      validation cohort (P<0.001 in Mann-Whitney U test; P<0.002 in Pearson's
      correlation analysis). Additionally, in both multivariate and univariate
      analyses, t(8;21)-positive patients categorized in a higher CNT3 expression
      tertile had longer disease-free survival [hazard ratio (HR), 0.117; 95%
      confidence interval (CI), 0.025-0.557; P=0.008] and overall survival (HR, 0.062;
      95% CI, 0.007-0.521; P=0.010) compared to t(8;21)-positive patients in a lower
      CNT3 expression tertile. Notably, these trends did not occur in t(8;21)-negative
      patients. Our results demonstrate that CNT3 expression is associated with overall
      favorable outcomes and is predictive of clinical outcomes in AML patients with
      t(8;21). This suggests that CNT3 expression can be used to optimize treatment
      strategies for AML patients. 

PMID- 25955570
TI  - Role of ROCK expression in gallbladder smooth muscle contraction.
AB  - Cholelithiasis is a common medical condition whose incidence rate is increasing
      yearly, while its pathogenesis has yet to be elucidated. The present study
      assessed the expression of Rho-kinase (ROCK) in gallbladder smooth muscles and
      its effect on the contractile function of gallbladder smooth muscles during
      gallstone formation. Thirty male guinea pigs were randomly divided into three
      groups: The control group, the gallstone model group and the fasudil interference
      group. The fasting volume (FV) and bile capacity of the gallbladder (FB) as well
      as the total cholesterol (TC) and triglyceride (TG) contents of the gallbladder
      bile were determined. In addition, the gallbladder was dissected to identify
      whether any gallstones had formed. Part of the gallbladder tissue specimens were
      used for immunohistochemical analysis of ROCK expression in gallbladder smooth
      muscles. The results showed that four guinea pigs in the model group and eight in
      the fasudil group displayed gallstone formation, while there was no gallstone
      formation in the control group. The FV and FB were significantly increased in the
      model and fasudil groups. Similarly, the TC and TG contents of gallbladder bile
      were increased in these groups. The positive expression rate of ROCK in
      gallbladder smooth muscles in the model and fasudil groups was significantly
      reduced compared with that in the control group (P<0.05). The results of the
      present study indicated that the reduction of ROCK expression in guinea pig
      gallbladder smooth muscles weakened gallbladder contraction and thereby promoted
      gallstone formation.

PMID- 25955568
TI  - Characterization of glioma stem-like cells from human glioblastomas.
AB  - Glioma stem-like cells (GSCs) could have potential for tumorigenesis, treatment
      resistance, and tumor recurrence (GSC hypothesis). However, the mechanisms
      underlying such potential has remained elusive and few ultrastructural features
      of the cells have been reported in detail. We therefore undertook observations of
      the antigenic characteristics and ultrastructural features of GSCs isolated from
      human glioblastomas. Tumor spheres formed by variable numbers of cells,
      exhibiting a variable appearance in both their size and shape, were frequently
      seen in GSCs expressing the stem cell surface markers CD133 and CD15. Increased
      cell nucleus atypia, mitochondria, rough endoplasmic reticulum, coated vesicles,
      and microvilli, were noted in the GSCs. Furthermore, cells at division phases and
      different phases of the apoptotic process were occasionally observed. These
      findings could imply that GSCs have certain relations with human neural stem
      cells (NSCs) but are primitively different from undifferentiated NSCs. The data
      may provide support for the GSC hypothesis, and also facilitate the establishment
      of future glioblastoma treatments targeting GSCs.

PMID- 25955571
TI  - Selective spleen tyrosine kinase inhibition delays autoimmune arthritis in mice.
AB  - Spleen tyrosine kinase (SYK) has an important role in immunoreceptor signaling,
      and SYK inhibition has accordingly attenuated immune-mediated injury in several
      models. Therefore, the present study examined the effect of SYK inhibition with
      the selective spleen tyrosine kinase inhibitor P505-15 in experimental rheumatoid
      arthritis (RA) using a murine model of collagen-induced arthritis (CIA).
      Treatment with the selective SYK inhibitor P505-15, a small molecule kinase
      inhibitor selective for SYK, led to a reduction in arthritis score and attenuated
      histological damage. P505-15 reduced cartilage destruction and macrophage
      infiltration in CIA mice. In addition, P505-15-treated mice showed lower
      circulating levels of type II-collagen immunoglobulin (Ig)G1 and IgG2 and pro
      inflammatory cytokines. Importantly, P505-15 treatment markedly reduced the
      interleukin 1beta-stimulated inflammatory response in human RA synovial cells.
      Given these encouraging results, a key function for SYK in the development of RA
      was identified, highlighting that SYK may be a potential therapeutic target for
      human RA.

PMID- 25955572
TI  - Evaluation of a high throughput method for the detection of mutations associated
      with thrombosis and hereditary hemochromatosis in Brazilian blood donors.
AB  - BACKGROUND: The aim of this study was to evaluate the OpenArray platform for
      genetic testing of blood donors and to assess the genotype frequencies of
      nucleotide-polymorphisms (SNPs) associated with venous thrombosis (G1691A and
      G20210A), hyperhomocysteinemia (C677T, A1298C), and hereditary hemochromatosis
      (C282Y, H63D and S65C) in blood donors from Sao Paulo, Brazil. METHODS: We
      examined 400 blood donor samples collected from October to November 2011. The
      SNPs were detected using OpenArray technology. The blood samples were also
      examined using a real-time PCR-FRET system to compare the results and determine
      the accuracy of the OpenArray method. RESULTS: We observed 100% agreement in all
      assays tested, except HFE C282Y, which showed 99.75% agreement. The HFE C282Y
      assay was further confirmed through direct sequencing, and the results showed
      that OpenArray analysis was accurate. The calculated frequencies of each SNP were
      FV G1691A 98.8% (G/G), 1.2% (G/A); FII G2021A 99.5% (G/G), 0.5% (G/A); MTHFR
      C677T 45.5% (C/C), 44.8% (C/T), 9.8% (T/T); MTHFR A1298C 60.3% (A/A), 33.6%
      (A/C), 6.1% (C/C); HFE C282Y 96%(G/G), 4%(G/A), HFE H63D 78.1%(C/C), 20.3% (C/G),
      1.6% (G/G); and HFE S65C 98.1% (A/A), 1.9% (A/T). CONCLUSION: Taken together,
      these results describe the frequencies of SNPs associated with diseases and are
      important to enhance our current knowledge of the genetic profiles of Brazilian
      blood donors, although a larger study is needed for a more accurate determination
      of the frequency of the alleles. Furthermore, the OpenArray platform showed a
      high concordance rate with standard FRET RT-PCR.

PMID- 25955573
TI  - Correction: Redefining the septal L-strut in septal surgery.

PMID- 25955574
TI  - Correction: Cell type-specific responses to wingless, hedgehog and
      decapentaplegic are essential for patterning early eye-antenna disc in
      Drosophila.

PMID- 25955575
TI  - Angiotensin II Induces an Increase in Matrix Metalloproteinase 2 Expression in
      Aortic Smooth Muscle Cells of Ascending Thoracic Aortic Aneurysms Through JNK,
      ERK1/2, and p38 MAPK Activation.
AB  - In this study, we hypothesized that angiotensin II (Ang II) induces matrix
      metalloproteinase 2 (MMP-2) upregulation in aneurysmal smooth muscle cells
      (ASMCs) derived from ascending thoracic aortic aneurysms (ATAAs). We compared MMP
      2 protein levels in ascending aortic specimens using Western blot and plasma
      concentrations by enzyme-linked immunosorbent assay between ATAA (n = 40) and
      coronary heart disease patients (n = 40). Additionally, the protein level of
      angiotensinogen (AGT) in the ascending aorta and the plasma concentration of Ang
      II were detected by Western blot and radioimmunoassay, respectively, in ATAA and
      coronary heart disease patients. In ATAA patients, Ang II and MMP-2 plasma levels
      were significantly increased (P < 0.05). Additionally, AGT and MMP-2 protein
      levels in the aorta of ATAA patients were higher (P < 0.01). Enhanced AGT
      suggested that the amount of Ang II in aneurysmal aorta specimens may be also
      increased, which was confirmed by immunofluorescent staining for Ang II.
      Moreover, we investigated the effect of Ang II on MMP-2 upregulation by ASMCs and
      determined the Ang II receptors and intracellular signaling pathways that are
      involved. Our results showed that treatment with Ang II significantly increased
      the expression of MMP-2 through the Ang II type 1 receptor (AT1R) and activated
      the 3 major mitogen-activated protein kinases (MAPKs), JNK, ERK1/2, and p38 MAPK.
      In conclusion, these results indicate that Ang II can induce MMP-2 expression
      elevation through AT1R and MAPK pathways in ASMCs and suggest that there is
      therapeutic potential for angiotensin receptor blocker drugs and MAPK inhibitors
      in the prevention and treatment of ATAAs. 

PMID- 25955576
TI  - Simulation and experimental verification of prompt gamma-ray emissions during
      proton irradiation.
AB  - Irradiation with protons and light ions offers new possibilities for tumor
      therapy but has a strong need for novel imaging modalities for treatment
      verification. The development of new detector systems, which can provide an in
      vivo range assessment or dosimetry, requires an accurate knowledge of the
      secondary radiation field and reliable Monte Carlo simulations. This paper
      presents multiple measurements to characterize the prompt gamma-ray emissions
      during proton irradiation and benchmarks the latest Geant4 code against the
      experimental findings. Within the scope of this work, the total photon yield for
      different target materials, the energy spectra as well as the gamma-ray depth
      profile were assessed. Experiments were performed at the superconducting AGOR
      cyclotron at KVI-CART, University of Groningen. Properties of the gamma-ray
      emissions were experimentally determined. The prompt gamma-ray emissions were
      measured utilizing a conventional HPGe detector system (Clover) and
      quantitatively compared to simulations. With the selected physics list
      QGSP_BIC_HP, Geant4 strongly overestimates the photon yield in most cases,
      sometimes up to 50%. The shape of the spectrum and qualitative occurrence of
      discrete gamma lines is reproduced accurately. A sliced phantom was designed to
      determine the depth profile of the photons. The position of the distal fall-off
      in the simulations agrees with the measurements, albeit the peak height is also
      overestimated. Hence, Geant4 simulations of prompt gamma-ray emissions from
      irradiation with protons are currently far less reliable as compared to
      simulations of the electromagnetic processes. Deviations from experimental
      findings were observed and quantified. Although there has been a constant
      improvement of Geant4 in the hadronic sector, there is still a gap to close. 

PMID- 25955577
TI  - Tuberculous Tracheobronchial Strictures Treated with Balloon Dilation: A Single
      Center Experience in 113 Patients during a 17-year Period.
AB  - PURPOSE: To evaluate the safety and effectiveness of balloon dilation in the
      treatment of tuberculous tracheobronchial strictures (TTBSs) in a series of 113
      patients at a single institution. MATERIALS AND METHODS: The institutional review
      board approved the study and waived the requirement to obtain informed consent.
      Between 1997 and 2014, under bronchoscopic and fluoroscopic guidance, a total of
      167 balloon dilation sessions were performed in 113 consecutive patients (14 male
      and 99 female patients; mean age, 37 years [age range, 17-73 years]), with a
      range of one to eight sessions per patient (mean, 1.5 sessions). Outcomes were
      number and/or frequency of balloon dilations, technical success, primary and
      secondary clinical success, improvement in respiratory status, airway patency
      rate, and alternative treatment after balloon dilation. A two-tailed paired t
      test and the Kaplan-Meier method were used to evaluate the improvement in
      respiratory status and airway patency rate after balloon dilation, respectively.
      RESULTS: Dilation was successful in 82 patients (73%) after single (n = 67) or
      multiple (n = 15) balloon dilations, with a mean follow-up of 30.3 months.
      Clinical failure occurred in 31 patients (27%). In these 31 patients, symptoms
      recurred 1 day to 113 months (mean, 13 months) after repeat balloon dilations.
      These 31 patients required alternative treatment, including temporary stent
      placement (n = 12), cutting balloon dilation (n = 12), radiation-eluting balloon
      dilation (n = 3), and surgery (n = 4). Before, immediately after, and 1 month
      after the procedure, pulmonary function test results showed significant
      improvements in mean forced vital capacity (P < .001), forced expiratory volume
      in 1 second (P = .001), forced expiratory flow in the midexpiratory phase (P =
      .020), and peak expiratory flow (P = .005). CONCLUSION: Balloon dilation of TTBSs
      is a safe, minimally invasive primary treatment that relieved symptoms in a large
      percentage of patients (73%). In patients with TTBSs refractory to balloon
      dilation, temporary stent placement, cutting balloon dilation, or radiation
      eluting balloon dilation can be an alternative treatment.

PMID- 25955578
TI  - Shear-Wave Elastography for the Preoperative Risk Stratification of Follicular
      patterned Lesions of the Thyroid: Diagnostic Accuracy and Optimal Measurement
      Plane.
AB  - PURPOSE: To evaluate the diagnostic accuracy of shear-wave elastography (SWE) for
      the diagnosis of malignancy in follicular lesions and to identify the optimal SWE
      measurement plane. MATERIALS AND METHODS: The institutional review board approved
      this HIPAA-compliant, single-institution, prospective pilot study. Subjects
      scheduled for surgery after a previous fine-needle aspiration report of "atypia
      of undetermined significance" or "follicular lesion of undetermined
      significance," "suspicion for follicular neoplasm," or "suspicion for Hurthle
      cell neoplasm," were enrolled after obtaining informed consent. Subjects
      underwent conventional ultrasonography (US), Doppler evaluation, and SWE
      preoperatively, and their predictive value for thyroid malignancy was evaluated
      relative to the reference standard of surgical pathologic findings. RESULTS:
      Thirty-five patients (12 men, 23 women) with a mean age of 55 years (range, 23-85
      years) and a fine-needle aspiration diagnosis of atypia of undetermined
      significance or follicular lesion of undetermined significance (n = 16),
      suspicion for follicular neoplasm (n = 14), and suspicion for Hurthle cell
      neoplasm (n = 5) were enrolled in the study. Male sex was a statistically
      significant (P = .02) predictor of malignancy, but age was not. No sonographic
      morphologic parameter, including nodule size, microcalcification,
      macrocalcification, halo sign, taller than wide dimension, or hypoechogenicity,
      was associated with malignancy. Similarly, no Doppler feature, including
      intranodular vascularity, pulsatility index, resistive index, or peak-systolic
      velocity, was associated with malignancy. Higher median SWE tissue Young modulus
      estimates from the transverse insonation plane were associated with malignancy,
      yielding an area under the receiver operating characteristic curve of 0.81 (95%
      confidence interval: 0.62, 1.00) for differentiation of malignant from benign
      nodules. At a cutoff value of 22.3 kPa, sensitivity, specificity, positive
      predictive value, and negative predictive value of 82%, 88%, 75%, and 91%,
      respectively, were observed. CONCLUSION: This prospective pilot study indicates
      that SWE may be a valuable tool in preoperative malignancy risk assessment of
      follicular-patterned thyroid nodules.

PMID- 25955579
TI  - Optimizing the US Diagnosis of Biliary Atresia with a Modified Triangular Cord
      Thickness and Gallbladder Classification.
AB  - Purpose To evaluate the diagnostic performance of ultrasonography (US) in the
      identification and exclusion of biliary atresia with a modified triangular cord
      thickness metric together with a gallbladder classification scheme, as well as
      hepatic artery (HA) diameter and liver and spleen size, in a large sample of
      jaundiced infants. Materials and Methods The ethics committee approved this
      study, and written informed parental consent was obtained. In 273 infants with
      conjugated hyperbilirubinemia (total bilirubin level >= 31.2 MUmol/L, with direct
      bilirubin level > indirect bilirubin level), detailed abdominal US was performed
      to exclude biliary atresia. Biliary atresia was found in 129 infants and ruled
      out in 144. A modified triangular cord thickness was measured at the anterior
      branch of the right portal vein, and a gallbladder classification scheme was
      identified that incorporated the appearance of the gallbladder and a gallbladder
      length-to-width ratio of up to 5.2 when the lumen was visualized, as well as HA
      diameter and liver and spleen size. Reference standard diagnosis was based on
      results of one or more of the following: surgery, liver biopsy, cholangiography,
      and clinical follow-up. Area under the receiver operating characteristic curve
      (AUC) analysis, binary logistic regression analysis, Fisher exact test, and
      unpaired t test were performed. Results Triangular cord thickness, HA diameter,
      ratio of gallbladder length to gallbladder width, liver size, and spleen size
      exhibited statistically significant differences (all P < .05) between the group
      with biliary atresia and the group without. AUCs of triangular cord thickness,
      ratio of gallbladder length to width, and HA diameter were 0.952, 0.844, and
      0.838, respectively. Logistic regression analysis demonstrated that these three
      US parameters were significantly associated (all P < .05) with biliary atresia.
      The combination of triangular cord thickness and gallbladder classification could
      yield comparable AUCs (0.915 vs 0.933, P = .400) and a higher sensitivity (96.9%
      vs 92.2%), compared with triangular cord thickness alone. Conclusion By using the
      combination of modified triangular cord thickness and gallbladder classification
      scheme, most infants with biliary atresia could be identified. ((c)) RSNA, 2015. 

PMID- 25955580
TI  - Association of Preoperative US Features and Recurrence in Patients with Classic
      Papillary Thyroid Carcinoma.
AB  - PURPOSE: To investigate whether ultrasonographic (US) features of thyroid nodules
      are associated with tumor recurrence in classic papillary thyroid carcinoma
      (PTC). MATERIALS AND METHODS: This retrospective study was approved by the
      Institutional Review Board, and the need to obtain informed consent was waived. A
      total of 515 patients (mean age, 45.8 years +/- 13.2 [standard deviation]; range,
      17-80 years) who underwent total thyroidectomy and central lymph node dissection
      for classic PTC greater than 10 mm from January 2003 to February 2006 and who
      were followed up for 12 months or longer were included. Malignant-appearing PTCs
      were defined as those showing at least one suspicious US feature among marked
      hypoechogenicity, irregular or microlobulated margin, microcalcifications, and
      taller-than-wide shape. Benign-appearing PTCs were defined as those without any
      suspicious US features. Kaplan-Meier cumulative-event curves for recurrence were
      compared by using the log-rank test. The multivariate Cox proportional hazard
      regression analysis was used to estimate hazard ratios (HRs) of the malignant
      appearing US features for recurrence in the preoperative, postoperative, and
      combined models. RESULTS: Fifty-six (10.9%) of 515 patients had recurrence.
      Malignant-appearing PTCs had lower 5- and 10-year disease-free survival rates
      compared with benign-appearing PTCs (P = .01). In the preoperative model,
      malignant-appearing US features (HR, 3.523; 95% confidence interval [CI]: 1.263,
      9.830) and larger nodule size (HR, 1.074; 95% CI: 1.051, 1.098) were
      independently associated with recurrence. In the combined model, male sex (HR,
      1.990; 95% CI: 1.098, 3.610), malignant-appearing US features (HR, 2.828; 95% CI:
      1.016. 7.870), larger nodule size (HR, 1.067; 95% CI: 1.043, 1.092),
      extrathyroidal extension (HR, 2.590; 95% CI: 1.160, 5.780), and lymph node
      metastasis (HR, 2.511; 95% CI: 1.163, 5.421) were independently associated with
      recurrence. CONCLUSION: The presence of malignant-appearing US features was
      independently associated with recurrence in patients with classic PTC.

PMID- 25955581
TI  - Synthetic Proteins Potently and Selectively Bind the Oncoprotein Gankyrin,
      Modulate Its Interaction with S6 ATPase, and Suppress Gankyrin/MDM2-Dependent
      Ubiquitination of p53.
AB  - Overexpression of the ankyrin repeat oncoprotein gankyrin is directly linked to
      the onset, proliferation, and/or metastasis of many cancers. The role of gankyrin
      in multiple disease-relevant biochemical processes is profound. In addition to
      other cellular processes, gankyrin overexpression leads to decreased cellular
      levels of p53, through a complex that involves MDM2. Thus, inhibition of this
      interaction is an attractive strategy for modulating oncogenic phenotypes in
      gankyrin-overexpressing cells. However, the lack of well-defined, hydrophobic,
      small-molecule binding pockets on the putative ankyrin repeat binding face
      presents a challenge to traditional small-molecule drug discovery. In contrast,
      by virtue of their size and relatively high folding energies, synthetic gankyrin
      binding proteins could, in principle, compete with physiologically relevant PPIs
      involving gankyrin. Previously, we showed that a shape-complementary protein
      scaffold can be resurfaced to bind gankyrin with moderate affinity (KD ~6 MUM).
      Here, we used yeast display high-throughput screening, error-prone PCR, DNA
      shuffling, and protein engineering to optimize this complex. The best of these
      proteins bind gankyrin with excellent affinity (KD ~21 nM), selectively co
      purifies with gankyrin from a complex cellular milieu, modulates an interaction
      between gankyrin and a physiological binding partner (S6 ATPase), and suppresses
      gankyrin/MDM2-dependent ubiquitination of p53. 

PMID- 25955582
TI  - Theoretical Investigation of Random Noise-Limited Signal-to-Noise Ratio in MR
      Based Electrical Properties Tomography.
AB  - In magnetic resonance imaging-based electrical properties tomography (MREPT),
      tissue electrical properties (EPs) are derived from the spatial variation of the
      transmit RF field (B1(+)). Here we derive theoretically the relationship between
      the signal-to-noise ratio (SNR) of the electrical properties obtained by MREPT
      and the SNR of the input B1(+) data, under the assumption that the latter is much
      greater than unity, and the noise in B1(+) at different voxels is statistically
      independent. It is shown that for a given B1(+) data, the SNR of both electrical
      conductivity and relative permittivity is proportional to the square of the
      linear dimension of the region of interest (ROI) over which the EPs are
      determined, and to the square root of the number of voxels in the ROI. The
      relationship also shows how the SNR varies with the main magnetic field (B0)
      strength. The predicted SNR is verified through numerical simulations on a
      cylindrical phantom with an analytically calculated B1(+) map, and is found to
      provide explanation of certain aspects of previous experimental results in the
      literature. Our SNR formula can be used to estimate minimum input data SNR and
      ROI size required to obtain tissue EP maps of desired quality. 

PMID- 25955583
TI  - Spatiotemporal Clutter Filtering of Ultrafast Ultrasound Data Highly Increases
      Doppler and fUltrasound Sensitivity.
AB  - Ultrafast ultrasonic imaging is a rapidly developing field based on the unfocused
      transmission of plane or diverging ultrasound waves. This recent approach to
      ultrasound imaging leads to a large increase in raw ultrasound data available per
      acquisition. Bigger synchronous ultrasound imaging datasets can be exploited in
      order to strongly improve the discrimination between tissue and blood motion in
      the field of Doppler imaging. Here we propose a spatiotemporal singular value
      decomposition clutter rejection of ultrasonic data acquired at ultrafast frame
      rate. The singular value decomposition (SVD) takes benefits of the different
      features of tissue and blood motion in terms of spatiotemporal coherence and
      strongly outperforms conventional clutter rejection filters based on high pass
      temporal filtering. Whereas classical clutter filters operate on the temporal
      dimension only, SVD clutter filtering provides up to a four-dimensional approach
      (3D in space and 1D in time). We demonstrate the performance of SVD clutter
      filtering with a flow phantom study that showed an increased performance compared
      to other classical filters (better contrast to noise ratio with tissue motion
      between 1 and 10mm/s and axial blood flow as low as 2.6 mm/s). SVD clutter
      filtering revealed previously undetected blood flows such as microvascular
      networks or blood flows corrupted by significant tissue or probe motion
      artifacts. We report in vivo applications including small animal fUltrasound
      brain imaging (blood flow detection limit of 0.5 mm/s) and several clinical
      imaging cases, such as neonate brain imaging, liver or kidney Doppler imaging. 

PMID- 25955584
TI  - 4D Blood Flow Reconstruction Over the Entire Ventricle From Wall Motion and Blood
      Velocity Derived From Ultrasound Data.
AB  - We demonstrate a new method to recover 4D blood flow over the entire ventricle
      from partial blood velocity measurements using multiple 3D+t colour Doppler
      images and ventricular wall motion estimated using 3D+t BMode images. We apply
      our approach to realistic simulated data to ascertain the ability of the method
      to deal with incomplete data, as typically happens in clinical practice.
      Experiments using synthetic data show that the use of wall motion improves
      velocity reconstruction, shows more accurate flow patterns and improves mean
      accuracy particularly when coverage of the ventricle is poor. The method was
      applied to patient data from 6 congenital cases, producing results consistent
      with the simulations. The use of wall motion produced more plausible flow
      patterns and reduced the reconstruction error in all patients. 

PMID- 25955585
TI  - Noise Suppression for Dual-Energy CT Through Entropy Minimization.
AB  - In dual energy CT (DECT), noise amplification during signal decomposition
      significantly limits the utility of basis material images. Since clinically
      relevant objects typically contain a limited number of different materials, we
      propose an Image-domain Decomposition method through Entropy Minimization (IDEM)
      for noise suppression in DECT. Pixels of decomposed images are first linearly
      transformed into 2D clusters of data points, which are highly asymmetric due to
      strong signal correlation. An optimal axis is identified in the 2D space via
      numerical search such that the projection of data clusters onto the axis has
      minimum entropy. Noise suppression is performed on each image pixel by estimating
      the center-of-mass value of each data cluster along the direction perpendicular
      to the projection axis. The IDEM method is distinct from other noise suppression
      techniques in that it does not suppress pixel noise by reducing spatial variation
      between neighboring pixels. As supported by studies on Catphan(c)600 and
      anthropomorphic head phantoms, this feature endows our algorithm with a unique
      capability of reducing noise standard deviation on DECT decomposed images by
      approximately one order of magnitude while preserving spatial resolution and
      image noise power spectra (NPS). Compared with a filtering method and recently
      developed iterative method at the same level of noise suppression, the IDEM
      algorithm obtains high-resolution images with less artifacts. It also maintains
      accuracy of electron density measurements with less than 2% bias error. The IDEM
      method effectively suppresses noise of DECT for quantitative use, with appealing
      features on preservation of image spatial resolution and NPS. 

PMID- 25955587
TI  - The glocal forest.
AB  - Spatial ecological patterns reflect the underlying processes that shape the
      structure of species and communities. Mechanisms like intra- and inter-specific
      competition, dispersal and host-pathogen interactions can act over a wide range
      of scales. Yet, the inference of such processes from patterns is a challenging
      task. Here we call attention to a quite unexpected phenomenon in the extensively
      studied tropical forest at the Barro-Colorado Island (BCI): the spatial
      deployment of (almost) all tree species is statistically equivalent, once
      distances are normalized by l0, the typical distance between neighboring
      conspecific trees. Correlation function, cluster statistics and nearest-neighbor
      distance distribution become species-independent after this rescaling. Global
      observables (species frequencies) and local spatial structure appear to be
      interrelated. This "glocality" suggests a radical interpretation of recent
      experiments that show a correlation between species' abundance and the negative
      feedback among conspecifics. For the forest to be glocal, the negative feedback
      must govern spatial patterns over all scales. 

PMID- 25955586
TI  - Protein and Peptide Composition of Male Accessory Glands of Apis mellifera Drones
      Investigated by Mass Spectrometry.
AB  - In honeybees, reproductive females usually mate early in their life with more
      than 10 males in free flight, often within 10 minutes, and then store male
      gametes for up to five years. Because of the extreme polyandry and mating in free
      flight special adaptations in males are most likely. We present here the results
      of an investigation of the protein content of four types of male reproductive
      glands from the Western honeybee (Apis mellifera) drone, namely seminal vesicles
      (secretion in ejaculate), as well as bulbus, cornua and mucus glands (secretions
      for the mating plug). Using high resolution and accuracy mass spectrometry and a
      combination of database searching and de novo sequencing techniques it was
      possible to identify 50 different proteins in total, inside all mentioned glands,
      except in the mucus gland. Most of the proteins are unique for a specific gland
      type, only one of them (H9KEY1/ATP synthase subunit O) was found in three glands,
      and 7 proteins were found in two types of glands. The identified proteins
      represent a wide variety of biological functions and can be assigned to several
      physiological classes, such as protection, energy generation, maintaining optimal
      conditions, associated mainly with vesicula seminalis; signaling, cuticle
      proteins, icarpin and apolipoproteins located mainly in the bulbus and cornua
      glands; and some other classes. Most of the discovered proteins were not found
      earlier during investigation of semen, seminal fluid and tissue of reproductive
      glands of the bee drone. Moreover, we provide here the origin of each protein.
      Thus, the presented data might shed light on the role of each reproductive gland.

PMID- 25955588
TI  - Polymorphism-Dependent Spin-Crossover: Hysteretic Two-Step Spin Transition with
      an Ordered [HS-HS-LS] Intermediate Phase.
AB  - A mononuclear iron(II) complex has been isolated in two polymorphs. Polymorph 1b
      remains high-spin over all temperatures, whereas polymorph 1a undergoes a
      cooperative two-step spin crossover accompanied by symmetry breaking, showing an
      ordered 2:1 high-spin-low-spin intermediate phase. 

PMID- 25955589
TI  - Ethnic Self-Identification, Ethnic Involvement, and Group Differentiation among
      Chinese Youth in the Netherlands.
AB  - Ethnic self-identification among Chinese minority youth living in the Netherlands
      was explored. Four types of ethnic self-identification were differentially
      related to ethnic involvement and to intergroup differentiation, suggesting that
      group identification may be less straightforward than researchers have assumed.
      Collectivism as an individual difference variable was related to ethnic self
      description and to ethnic involvement. In-group favoritism and an in-group
      homogeneity effect (both of which may be a function of the Chinese minority
      position in the Netherlands or of the Chinese collectivist culture) were evident.

PMID- 25955590
TI  - The case of active and inactive quality circles.
AB  - Active and inactive quality circles (QCs; small groups of employees that solve
      organizational problems) were studied during the first 3 months (Times 1, 2, and
      3) and the last 3 months (Times 4, 5, and 6) of their existence. The results
      indicated that both active and inactive QCs tended to have more members during
      the first 3 months than during the last 3 months. Membership in inactive QCs
      decreased significantly from Time 5 to Time 6, in contrast to membership in
      active QCs, which did not change during this period, and active QCs tended to
      have more members than inactive QCs did at Time 6. Thus, a significant decrease
      in QC membership may forecast disbandment. 

PMID- 25955591
TI  - The impact of group discussion on the theory-perseverance bias.
AB  - The theory-perseverance bias was investigated in 3 related studies. In Study 1, a
      test of the hypothesis that group discussion attenuates this bias, male and
      female Canadian undergraduates examined information suggesting that either a
      positive or a negative relationship exists between risk preference and
      firefighting performance; they were then informed that this information was
      fictitious. They then recorded their beliefs regarding the actual relationship
      between these variables (a) immediately, (b) after 7 min of thought, (c) after a
      7-min group discussion, or (d) after perusing a transcript of one of the
      discussions. Only the participants in the first condition made biased judgments.
      Study 2, which used Vinokur and Burnstein's (1974) procedures and which again
      drew a sample of Canadian students, provided support for a persuasive-arguments
      explanation of this group-discussion effect. The results of Study 3, which used
      procedures similar to those of Study 1, ruled out a social-comparison explanation
      for this effect. Factors that might enhance or diminish the effects of group
      discussion on this bias are suggested. 

PMID- 25955592
TI  - Age and embarrassment at others' gaffes.

PMID- 25955593
TI  - Visibility and negotiating flexibility.

PMID- 25955594
TI  - Three-dimensional love.

PMID- 25955595
TI  - Anxiety Level and its Temporal Change among Working Mothers in Calcutta.

PMID- 25955596
TI  - The attributional style of repressive individuals.

PMID- 25955597
TI  - A Novel Bioresorbable Implant for Repair of Orbital Floor Fractures.
AB  - PURPOSE: To describe clinical, radiologic, and safety outcomes of orbital floor
      fracture repair using a novel bioresorbable polycaprolactone (PCL) mesh implant
      (OsteomeshTM, Osteopore International, Singapore). METHODS: This is a prospective
      interventional case series of orbital floor fractures repaired using a novel PCL
      mesh implant. Clinical evaluation was conducted at presentation and
      postoperatively at 1, 4, 12, 24 and 48 weeks. Computed tomography (CT) of the
      orbits was performed 1 year postoperatively. RESULTS: A total of 20 patients were
      recruited. Mean follow up was 50.4 +/- 31.88 weeks. The majority of the patients
      were male (60%) and of Chinese ethnicity (75%), and the mean age was 39.35 (range
      13-69) years. The most common mechanism of injury was assault. The average
      fracture size was 21.9 mm (range 12-32 mm) in the anteroposterior meridian and
      18.65 mm (range 6-27 mm) in the horizontal meridian. Fifty percent of the
      patients were classified as having a large orbital defect (horizontal width >=20
      mm). The binocular single vision (BSV) score improved from 72.1% preoperatively
      to 90.8% postoperatively (P < 0.05) for 17 patients who had pre and postoperative
      charts. BSV improvement did not differ significantly between those with large and
      small orbital fracture sizes. There were features of neobone formation on CT scan
      performed 1.5 years after implantation. CONCLUSION: This bioresorbable implant is
      a promising material for the repair of both small and large orbital floor
      fractures, giving good functional and aesthetic outcomes.

PMID- 25955598
TI  - Methylation of the tryptophan hydroxylase-2 gene is associated with mRNA
      expression in patients with major depression with suicide attempts.
AB  - Tryptophan hydroxylase-2 (TPH2) contributes to alterations in the function of
      neuronal serotonin (5-HT), which are associated with various psychopathologies,
      including major depressive disorder (MDD) or suicidal behavior. The methylation
      of a single CpG site in the promoter region of TPH2 affects gene expression.
      Suicide and MDD are strongly associated and genetic factors are at least
      partially responsible for the variability in suicide risk. The aim of the present
      study was to investigate whether variations in TPH2 methylation in peripheral
      blood samples may predispose patients with MDD to suicide attempts. TPH2 mRNA
      expression levels differed significantly between 50 patients with MDD who had
      attempted suicide (MDD + suicide group) and 75 control patients with MDD (MDD
      group); TPH2 expression levels were significantly decreased (P=0.0005) in the
      patients who had attempted suicide. Furthermore, the frequency of TPH2
      methylation was 36.0% in the MDD + suicide group, while it was 13.0% in the MDD
      group. The results of the present study demonstrated that methylation in the
      promoter region of TPH2 significantly affected the mRNA expression levels of
      TPH2, thus suggesting that methylation of the TPH2 promoter may silence TPH2 mRNA
      expression in MDD patients with or without suicidal behavior. In addition, there
      was a significant correlation between the methylation status of the TPH2 promoter
      and depression, hopelessness and cognitive impairment in the MDD + suicide group.
      In conclusion, the present study demonstrated that TPH2 expression was regulated
      by DNA methylation of the TPH2 promoter region in patients with MDD.

PMID- 25955599
TI  - Development of a high throughput luciferase reporter gene system for screening
      activators and repressors of human collagen Ialpha2 gene expression.
AB  - Fibrosis, which is characterized by the excessive production of matrix proteins,
      occurs in multiple tissues and is associated with increased morbidity and
      mortality. Despite its significant negative impact on patient outcomes, therapies
      targeted to treat fibrosis are currently lacking. Screening for inhibitors of the
      expression of collagen, the primary component of fibrotic lesions, represents an
      option for the identification of novel lead compounds for therapeutic development
      with potentially fewer off-target effects compared with the targeting of
      multifunctional cell signaling pathways. Here we report on the generation of a
      stable luciferase reporter system using a fibroblast cell line, which can be used
      for rapidly screening both activators and repressors of human collagen COL1A2
      gene transcription in a high throughput setting. This in vitro screening tool was
      validated using known agonists (scleraxis, TGF-beta, angiotensin II, CTGF) and
      antagonists (TNF-alpha, pirfenidone) of COL1A2 gene expression. The COL1A2-luc
      NIH-3T3 fibroblast system provides a useful and effective screen for potential
      lead compounds with pro- or anti-fibrotic properties. 

PMID- 25955600
TI  - Drosophila ovipositor extension in mating behavior and egg deposition involves
      distinct sets of brain interneurons.
AB  - Oviposition is a female-specific behavior that directly affects fecundity, and
      therefore fitness. If a fertilized female encounters another male that she has
      evaluated to be of better quality than her previous mate, it would be beneficial
      for her to remate with this male rather than depositing her eggs. Females who
      decided not to remate exhibited rejection behavior toward a courting male and
      engaged in oviposition. Although recent studies of Drosophila melanogaster
      identified sensory neurons and putative second-order ascending interneurons that
      mediate uterine afferents affecting female reproductive behavior, little is known
      about the brain circuitry that selectively activates rejection versus oviposition
      behaviors. We identified the sexually dimorphic pC2l and female-specific pMN2
      neurons, two distinct classes of doublesex (dsx)-expressing neurons that can
      initiate ovipositor extension associated with rejection and oviposition behavior,
      respectively. pC2l interneurons, which induce ovipositor extrusion for rejection
      in females, have homologues that control courtship behavior in males. Activation
      of these two classes of neurons appears to be mutually exclusive and each governs
      hierarchical control of the motor program in the VNC either for rejection or
      oviposition, contributing centrally to the switching on or off of the alternative
      motor programs. 

PMID- 25955601
TI  - A case of tooth autotransplantation after long-term cryopreservation using a
      programmed freezer with a magnetic field.
AB  - This case report describes the treatment of a skeletal Class III malocclusion
      with autotransplantation of a cryopreserved tooth. To gain an esthetic facial
      profile and good occlusion, extraction of bimaxillary premolars and surgical
      therapy were chosen. The patient had chronic apical periodontitis on the lower
      left first molar. Although she did not feel any pain in that region, the tooth
      was considered to have a poor prognosis. Therefore, we cryopreserved the
      extracted premolars to prepare for autotransplantation in the lower first molar
      area because the tooth would probably need to be removed in the future. The teeth
      were frozen by a programmed freezer with a magnetic field (CAS freezer) that was
      developed for tissue cryopreservation and were cryopreserved in -150 degrees C
      deep freezer. After 1.5 years of presurgical orthodontic treatment, bilateral
      sagittal split ramus osteotomy was performed for mandible setback. Improvement of
      the facial profile and the occlusion were achieved in the retention phase. Six
      years after the initial visit, the patient had pain on the lower left first
      molar, and discharge of pus was observed, so we extracted the lower left first
      molar and autotransplanted the cryopreserved premolar. Three years later, healthy
      periodontium was observed at the autotransplanted tooth. This case report
      suggests that long-term cryopreservation of teeth by a CAS freezer is useful for
      later autotransplantation, and this can be a viable technique to replace missing
      teeth. 

PMID- 25955602
TI  - Saying "good-bye" and "thank you" to a legendary figure in orthodontics.

PMID- 25955603
TI  - An Orthodontist looks at 50...

PMID- 25955604
TI  - Re: Mandibular growth comparisons of Class I and Class II division 1
      skeletofacial patterns by Helder B. Jacob, Peter H. Buschang. The Angle Orthod.
      2014;84:755-761.

PMID- 25955605
TI  - Re Response to: Mandibular growth comparisons of Class I and Class II division 1
      skeletofacial patterns by Helder B. Jacob and Peter H. Buschang. The Angle
      Orthod. 2014;84:755-761.

PMID- 25955607
TI  - The use of information and communications technologies in the delivery of
      interprofessional education: A review of evaluation outcome levels.
AB  - Interprofessional education (IPE) in health and human services educational and
      clinical settings has proliferated internationally. The use of information and
      communication technologies (ICTs) in the facilitation of interprofessional
      learning is also growing, yet reviews of the effectiveness of ICTs in the
      delivery of pre- and/or post-licensure IPE have been limited. The current study's
      purpose was to review the evaluation outcomes of IPE initiatives delivered using
      ICTs. Relevant electronic databases and journals from 1996 to 2013 were searched.
      Studies which evaluated the effectiveness of an IPE intervention using ICTs were
      included and analyzed using the Barr et al. modified Kirkpatrick educational
      outcomes typology. Fifty-five studies were identified and a majority reported
      evaluation findings at the level 1 (reaction/satisfaction). Analysis revealed
      that learners react favorably to the use of ICTs in the delivery of IPE, and ICT
      mediated IPE can lead to positive attitudinal and knowledge change. A majority of
      the studies reported positive evaluation outcomes at the learner satisfaction
      level, with the use of web-based learning modalities. The limited number of
      studies at other levels of the outcomes typology and deficiencies in study
      designs indicate the need for more rigorous evaluation of outcomes in ICT
      mediated IPE.

PMID- 25955608
TI  - Digoxin Suppresses Tumor Malignancy through Inhibiting Multiple Src-Related
      Signaling Pathways in Non-Small Cell Lung Cancer.
AB  - Non-small cell lung cancer is the predominant type of lung cancer, resulting in
      high mortality worldwide. Digoxin, a cardiac glycoside, has recently been
      suggested to be a novel chemotherapeutic agent. Src is an oncogene that plays an
      important role in cancer progression and is therefore a potential target for
      cancer therapy. Here, we investigated whether digoxin could suppress lung cancer
      progression through the inhibition of Src activity. The effects of digoxin on
      lung cancer cell functions were investigated using colony formation, migration
      and invasion assays. Western blotting and qPCR assays were used to analyze the
      mRNA and protein expression levels of Src and its downstream proteins, and a cell
      viability assay was used to measure cellular cytotoxicity effects. The results of
      the cell function assays revealed that digoxin inhibited the proliferation,
      invasion, migration, and colony formation of A549 lung cancer cells. Similar
      effects of digoxin were also observed in other lung cancer cell lines.
      Furthermore, we found that digoxin significantly suppressed Src activity and its
      protein expression in a dose- and time-dependent manner as well as reduced EGFR
      and STAT3 activity. Our data suggest that digoxin is a potential anticancer agent
      that may suppress lung cancer progression through inhibiting Src and the activity
      of related proteins. 

PMID- 25955617
TI  - Protein-Protein Communication and Enzyme Activation Mediated by a Synthetic
      Chemical Transducer.
AB  - The design and function of a synthetic "chemical transducer" that can generate an
      unnatural communication channel between two proteins is described. Specifically,
      we show how this transducer enables platelet-derived growth factor to trigger (in
      vitro) the catalytic activity of glutathione-s-transferase (GST), which is not
      its natural enzyme partner. GST activity can be further controlled by adding
      specific oligonucleotides that switch the enzymatic reaction on and off. We also
      demonstrate that a molecular machine, which can regulate the function of an
      enzyme, could be used to change the way a prodrug is activated in a
      "programmable" manner. 

PMID- 25955609
TI  - Deregulation of genes related to iron and mitochondrial metabolism in refractory
      anemia with ring sideroblasts.
AB  - The presence of SF3B1 gene mutations is a hallmark of refractory anemia with ring
      sideroblasts (RARS). However, the mechanisms responsible for iron accumulation
      that characterize the Myelodysplastic Syndrome with ring sideroblasts (MDS-RS)
      are not completely understood. In order to gain insight in the molecular basis of
      MDS-RS, an integrative study of the expression and mutational status of genes
      related to iron and mitochondrial metabolism was carried out. A total of 231 low
      risk MDS patients and 81 controls were studied. Gene expression analysis revealed
      that iron metabolism and mitochondrial function had the highest number of genes
      deregulated in RARS patients compared to controls and the refractory cytopenias
      with unilineage dysplasia (RCUD). Thus mitochondrial transporters SLC25 (SLC25A37
      and SLC25A38) and ALAD genes were over-expressed in RARS. Moreover, significant
      differences were observed between patients with SF3B1 mutations and patients
      without the mutations. The deregulation of genes involved in iron and
      mitochondrial metabolism provides new insights in our knowledge of MDS-RS. New
      variants that could be involved in the pathogenesis of these diseases have been
      identified. 

PMID- 25955619
TI  - Determination of photoluminescence quantum yields of scattering media with an
      integrating sphere: direct and indirect illumination.
AB  - The ever-increasing use of fluorescent nanomaterials and micrometer-sized beads
      in the life and material sciences requires reliable procedures for the
      measurement of the key performance parameter fluorescence quantum yield (Phif) of
      scattering particle dispersions and reference systems to evaluate the performance
      of such measurements. This encouraged us to systematically study, both
      theoretically and experimentally, the optical determination of photoluminescent
      quantum yield as a function of the scattering and absorption properties of the
      sample and the illumination geometry with an integrating sphere method. The
      latter included measurements with a direct and an indirect illumination. As a
      representative and easy-to-prepare reference system, we used ethanolic
      dispersions of 250 nm sized silica particles and the dye rhodamine 101 and
      systematically varied the concentration of the dye and particles within the
      typical ranges of spectroscopic and (bio)analytical applications of fluorescent
      nanomaterials. Based on our measurements, we recommend indirect sample
      illumination geometry for the accurate measurement of Phif of samples with low or
      unknown absorption and high scattering coefficients such as dispersions of
      luminescent particles or fluorescent reporters in biological matrices. This
      finding is of utmost relevance for all (bio)analytical applications of
      fluorescent nanomaterials ranging from particle labels and probes over assay
      platforms to safety barcodes. 

PMID- 25955618
TI  - Fbxw7 regulates hepatocellular carcinoma migration and invasion via Notch1
      signaling pathway.
AB  - Hepatocellular carcinoma (HCC) is one of the most common human malignancies and
      also the leading cause of cancer-related death in the world. The mechanisms
      underlying the progression and metastasis of HCC remain unclear. The E3 ubiquitin
      ligase F-box and WD repeat domain-containing 7 (Fbxw7) is broadly considered as a
      tumor suppressor gene. However, the role of Fbxw7 in HCC is not clear. To
      investigate the expression and biological functions of Fbxw7 in HCC, we examined
      Fbxw7 expression level using HCC tissue microarray and immunohistochemistry. Our
      data showed that Fbxw7 expression is significantly reduced in HCC compared with
      non-cancerous tissues (P<0.05). Fbxw7 levels were significantly associated with
      tumor differentiation (P=0.013), the incidence of portal or hepatic venous
      invasion (P=0.031), metastasis (P=0.027) and AJCC cancer stage (P=0.047). Then,
      we observed a strong correlation between low Fbxw7 expression and a worse 5-year
      survival of HCC patients (P<0.001). Furthermore, multivariate Cox regression
      analyses demonstrated that the Fbxw7 expression (P<0.001) was an independent
      factor for the prediction of the overall survival of HCC patients. We also found
      that both Fbxw7 mRNA and protein levels were significantly reduced in HCC cell
      lines compared with human liver non-tumor cell line. Moreover, our in vitro
      experiments showed a remarkable increase of cell migration and invasion in Fbxw7
      knockdown cells and a decrease in Fbxw7-overexpress cells. In addition, the
      present study demonstrated that Fbxw7 is involved in the migration and invasion
      of HCC cells via regulating Notch1 and the downstream molecules of Notch1. Taken
      together, our findings indicate that Fbxw7 can be used as a prognostic marker; it
      has an important role in HCC progression and inhibits HCC cell migration and
      invasion through the Notch1 signaling pathway.

PMID- 25955620
TI  - AAFP Reiterates Warning to CMS About Provider Network Inadequacy.

PMID- 25955621
TI  - Should family physicians screen for testosterone deficiency in men? Yes:
      screening for testosterone deficiency is worthwhile for most older men.

PMID- 25955622
TI  - Should family physicians screen for testosterone deficiency in men? No: screening
      may be harmful, and benefits are unproven.

PMID- 25955623
TI  - New-onset bullous rash.

PMID- 25955624
TI  - Diagnosis and Treatment of Peptic Ulcer Disease and H. pylori Infection.
AB  - The most common causes of peptic ulcer disease (PUD) are Helicobacter pylori
      infection and use of nonsteroidal anti-inflammatory drugs (NSAIDs). The test-and
      treat strategy for detecting H. pylori is appropriate in situations where the
      risk of gastric cancer is low based on age younger than 55 years and the absence
      of alarm symptoms. Most other patients should undergo upper endoscopy to rule out
      malignancy and other serious causes of dyspepsia. Urea breath tests and stool
      antigen tests are most accurate for identifying H. pylori infection and can be
      used to confirm cure; serologic tests are a convenient but less accurate
      alternative and cannot be used to confirm cure. Treatment choices include
      standard triple therapy, sequential therapy, quadruple therapy, and levofloxacin
      based triple therapy. Standard triple therapy is only recommended when resistance
      to clarithromycin is low. Chronic use of NSAIDs in patients with H. pylori
      infection increases the risk of PUD. Recommended therapies for preventing PUD in
      these patients include misoprostol and proton pump inhibitors. Complications of
      PUD include bleeding, perforation, gastric outlet obstruction, and gastric
      cancer. Older persons are at higher risk of PUD because of high-risk medication
      use, including antiplatelet drugs, warfarin, selective serotonin reuptake
      inhibitors, and bisphosphonates.

PMID- 25955626
TI  - Lung cancer: diagnosis, treatment principles, and screening.
AB  - Lung cancer is classified histologically into small cell and non-small cell lung
      cancers. The most common symptoms of lung cancer are cough, dyspnea, hemoptysis,
      and systemic symptoms such as weight loss and anorexia. High-risk patients who
      present with symptoms should undergo chest radiography. If a likely alternative
      diagnosis is not identified, computed tomography and possibly positron emission
      tomography should be performed. If suspicion for lung cancer is high, a
      diagnostic evaluation is warranted. The diagnostic evaluation has three
      simultaneous steps (tissue diagnosis, staging, and functional evaluation), all of
      which affect treatment planning and determination of prognosis. The least
      invasive method possible should be used. The diagnostic evaluation and treatment
      of a patient with lung cancer require a team of specialists, including a
      pulmonologist, medical oncologist, radiation oncologist, pathologist,
      radiologist, and thoracic surgeon. Non-small cell lung cancer specimens are
      tested for various mutations, which, if present, can be treated with new targeted
      molecular therapies. The family physician should remain involved in the patient's
      care to ensure that the values and wishes of the patient and family are
      considered and, if necessary, to coordinate end-of-life care. Early palliative
      care improves quality of life and may prolong survival. Family physicians should
      concentrate on early recognition of lung cancer, as well as prevention by
      encouraging tobacco cessation at every visit. The U.S. Preventive Services Task
      Force recommends lung cancer screening using low-dose computed tomography in high
      risk patients. However, the American Academy of Family Physicians concludes that
      the evidence is insufficient to recommend for or against screening. Whether to
      screen high-risk patients should be a shared decision between the physician and
      patient.

PMID- 25955625
TI  - Hemoptysis: evaluation and management.
AB  - Hemoptysis is the expectoration of blood from the lung parenchyma or airways. The
      initial step in the evaluation is determining the origin of bleeding.
      Pseudohemoptysis is identified through the history and physical examination. In
      adults, acute respiratory tract infections (e.g., bronchitis, pneumonia),
      bronchiectasis, asthma, chronic obstructive pulmonary disease, and malignancy are
      the most common causes. Tuberculosis is a major cause of hemoptysis in endemic
      regions of the world. Although tuberculosis rates are low in the United States,
      they are increased in persons who are homeless or who were born in other
      countries; consideration for testing should be made on an individual basis.
      Hemodynamic instability, abnormal gas exchange, cardiopulmonary comorbidities,
      and lesions at high risk of massive bleeding warrant inpatient evaluation. Chest
      radiography is recommended as the initial diagnostic test for hemodynamically
      stable patients with hemoptysis. Further evaluation with computed tomography with
      or without bronchoscopy is recommended in patients with massive hemoptysis, those
      with abnormal radiographic findings, and those with risk factors for malignancy
      despite normal radiographic findings.

PMID- 25955627
TI  - Screening for primary hypertension in children and adolescents.

PMID- 25955635
TI  - Lung cancer.

PMID- 25955636
TI  - H. pylori and Stomach Ulcers: What You Should Know.

PMID- 25955637
TI  - The Complete Sequence of the Acacia ligulata Chloroplast Genome Reveals a Highly
      Divergent clpP1 Gene.
AB  - Legumes are a highly diverse angiosperm family that include many agriculturally
      important species. To date, 21 complete chloroplast genomes have been sequenced
      from legume crops confined to the Papilionoideae subfamily. Here we report the
      first chloroplast genome from the Mimosoideae, Acacia ligulata, and compare it to
      the previously sequenced legume genomes. The A. ligulata chloroplast genome is
      174,233 bp in size, comprising inverted repeats of 38,225 bp and single-copy
      regions of 92,798 bp and 4,985 bp [corrected]. Acacia ligulata lacks the
      inversion present in many of the Papilionoideae, but is not otherwise
      significantly different in terms of gene and repeat content. The key feature is
      its highly divergent clpP1 gene, normally considered essential in chloroplast
      genomes. In A. ligulata, although transcribed and spliced, it probably encodes a
      catalytically inactive protein. This study provides a significant resource for
      further genetic research into Acacia and the Mimosoideae. The divergent clpP1
      gene suggests that Acacia will provide an interesting source of information on
      the evolution and functional diversity of the chloroplast Clp protease complex.

PMID- 25955640
TI  - Unaided visual acuity and blur: a simple model.
AB  - PURPOSE: This article proposes a simple model that describes the quantitative
      relationship between unaided visual acuity and blur attributed to refractive
      errors. METHODS: The standard model for describing the relationship between
      visual acuity and blur, as published by Raasch, is used as a starting point to
      develop a simpler model based on heuristic arguments. The basis of Raasch's data
      is augmented by published findings in the range of low-level refractive errors.
      Sphero-cylindrical refractive errors are transformed into a single blur quantity
      b, also termed dioptric distance, which serves as an input in both models. The
      possible influence of the cylinder axis and the pupil size is not included.
      RESULTS: The quite simple model for the unaided minimum angle of resolution, MAR
      ? 1+ b(2), nicely matches available data and improves the SE of the regression by
      a factor of 2 in comparison to Raasch's model. CONCLUSIONS: Both models
      considered in this article describe measurement data equally well. They differ in
      terms of complexity and functional form. The simple model provides a valid
      description for low-level refractive errors, where Raasch's model fails. Actual
      uncertainties in experimental data on unaided visual acuity, especially the
      frequent lack of information on pupil diameter, prevent meaningful numerical
      comparison and the refinement of both models. However, theoretical arguments are
      provided in support of the simple model.

PMID- 25955638
TI  - Development of the Corticospinal and Callosal Tracts from Extremely Premature
      Birth up to 2 Years of Age.
AB  - White matter tracts mature asymmetrically during development, and this
      development can be studied using diffusion magnetic resonance imaging. The aims
      of this study were i. to generate dynamic population-averaged white matter
      registration templates covering in detail the period from 25 weeks gestational
      age to term, and extending to 2 years of age based on DTI and fractional
      anisotropy, ii. to produce tract-specific probability maps of the corticospinal
      tracts, forceps major and forceps minor using probabilistic tractography, and
      iii. to assess the development of these tracts throughout this critical period of
      neurodevelopment. We found evidence for asymmetric development across the fiber
      bundles studied, with the corticospinal tracts showing earlier maturation (as
      measured by fractional anisotropy) but slower volumetric growth compared to the
      callosal fibers. We also found evidence for an anterior to posterior gradient in
      white matter microstructure development (as measured by mean diffusivity) in the
      callosal fibers, with the posterior forceps major developing at a faster rate
      than the anterior forceps minor in this age range. Finally, we report a protocol
      for delineating callosal and corticospinal fibers in extremely premature cohorts,
      and make available population-averaged registration templates and a probabilistic
      tract atlas which we hope will be useful for future neonatal and infant white
      matter imaging studies. 

PMID- 25955641
TI  - Teleretinal imaging for detection of referable macular degeneration.
AB  - PURPOSE: The purpose of this study was to determine the sensitivity and
      specificity for detection of referable age-related macular degeneration (AMD)
      using an existing nonmydriatic telemedicine pathway for diabetic retinopathy
      screening with comparison to same-day face-to-face examination by a retina
      specialist. METHODS: Subjects in this study underwent nonmydriatic and mydriatic
      digital retinal imaging on the same day as stereoscopic dilated examination of
      the macula by a retina specialist and the level of AMD was recorded for each eye.
      Images were graded by two trained readers as nonreferable or referable (AREDS
      [Age-Related Eye Disease Study] grading of level 3 or greater). Sensitivity and
      specificity were calculated by comparing referral recommendations between each
      reader and the retina specialist ("gold standard"). RESULTS: There were 47
      subjects (94 eyes) enrolled in the study. Sensitivity for nonreferable AMD with
      nonmydriatic imaging was 1.0 (reader 1) and 1.0 (reader 2), whereas specificity
      was 0.75 (reader 1) and 0.91 (reader 2). Sensitivity for referable AMD with
      nonmydriatic imaging was 0.84 (reader 1) and 0.88 (reader 2), whereas specificity
      was 0.81 (reader 1) and 0.81 (reader 2). CONCLUSIONS: Our study showed that
      nonmydriatic digital retinal imaging had excellent sensitivity and specificity in
      identifying referable and nonreferable AMD using an existing validated
      telemedicine pathway for diabetic retinopathy screening.

PMID- 25955639
TI  - Pseudomonas aeruginosa Survival at Posterior Contact Lens Surfaces after Daily
      Wear.
AB  - PURPOSE: Pseudomonas aeruginosa keratitis is a sight-threatening complication of
      contact lens wear, yet mechanisms by which lenses predispose to infection remain
      unclear. Here, we tested the hypothesis that tear fluid at the posterior contact
      lens surface can lose antimicrobial activity over time during lens wear. METHODS:
      Daily disposable lenses were worn for 1, 2, 4, 6, or 8 hours immediately after
      removal from their packaging or after presoaking in sterile saline for 2 days to
      remove packaging solution. Unworn lenses were also tested, some coated in tears
      "aged" in vitro for 1 or 8 hours. Lenses were placed anterior surface down into
      tryptic soy agar cradles containing gentamicin (100 MUg/mL) to kill bacteria
      already on the lens and posterior surfaces inoculated with gentamicin-resistant
      P. aeruginosa for 3 hours. Surviving bacteria were enumerated by viable counts of
      lens homogenates. RESULTS: Posterior surfaces of lenses worn by patients for 8
      hours supported more P. aeruginosa growth than lenses worn for only 1 hour, if
      lenses were presoaked before wear (~ 2.4-fold, p = 0.01). This increase was
      offset if lenses were not presoaked to remove packaging solution (p = 0.04 at 2
      and 4 hours). Irrespective of presoaking, lenses worn for 8 hours showed more
      growth on their posterior surface than unworn lenses coated with tear fluid that
      was aged for 8 hours in vitro (~ 8.6-fold, presoaked, p = 0.003; ~ 5.4-fold from
      packaging solution, p = 0.004). Indeed, in vitro incubation did not impact tear
      antimicrobial activity. CONCLUSIONS: This study shows that postlens tear fluid
      can lose antimicrobial activity over time during contact lens wear, supporting
      the idea that efficient tear exchange under a lens is critical for homeostasis.
      Additional studies are needed to determine applicability to other lens types,
      wearing modalities, and relevance to contact lens-related infections.

PMID- 25955642
TI  - Comparison of Self-applied Heat Therapy for Meibomian Gland Dysfunction.
AB  - PURPOSE: To compare the effects on ocular temperature, lipid layer grade, tear
      film stability, and tear meniscus height after a single application of two
      commercially available warm compresses in mild-to-moderate dry eye and to report
      participant treatment preference. METHODS: Forty-one subjects with mild-to
      moderate dry eye symptoms were enrolled in a randomized, paired-eye, investigator
      masked trial. Heat was applied simultaneously to one eye (randomized) with a
      portable eye mask (EyeGiene) and to the contralateral eye with a microwave-heated
      flaxseed eye bag (MGDRx Eye Bag). Outer and inner eyelid temperatures, tear film
      lipid layer grade (LLG), and noninvasive tear film breakup time (NIBUT) were
      measured at baseline and immediately after 10 minutes of device application.
      RESULTS: Outer and inner eyelid temperatures, LLG, and NIBUT did not differ
      before treatment between eyes assigned to eye mask and eye bag therapy. All
      measurements were significantly increased from baseline, after warming with both
      devices (all p < 0.05). Outer and inner eyelid temperature changes were
      significantly greater with the eye bag than with the eye mask (outer eyelid, +3.5
      +/- 1.0 degrees C vs. +2.4 +/- 0.8 degrees C; inner eyelid, +3.5 +/- 1.0 degrees
      C vs. +2.5 +/- 0.9 degrees C; all p < 0.001), although there was no significant
      difference in LLG and NIBUT improvement between treatments (all p > 0.05). A
      majority of subjects (78%) preferred the application of heat with the eye bag
      over the eye mask. CONCLUSIONS: Both the EyeGiene mask and the MGDRx Eye Bag are
      convenient eyelid warming devices that result in clinically and statistically
      significant increases in NIBUT and LLG in patients with mild-to-moderate dry eye
      symptoms. The MGDRx Eye Bag is more effective in raising ocular temperature and
      is the preferred treatment method among subjects.

PMID- 25955643
TI  - Distribution of cataract surgical rate and its economic inequality in Iran.
AB  - PURPOSE: To determine the distribution of the cataract surgical number per
      million population per year (CSR), the CSR in the population older than 50 years
      (CSR 50+) in the provinces of Iran, and their economic inequality in 2010.
      METHODS: As part of the cross-sectional 2011 CSR survey, the provincial CSR and
      CSR 50+ were calculated as the total number of surgeries in major and minor
      centers divided by the total population and the population older than 50 years in
      each province. Economic inequality was determined using the average province
      income, the average urban and rural household incomes, and the percentage of
      urban and rural population in each province. RESULTS: Tehran and Ilam provinces
      had the highest and lowest CSR (12,465 vs. 359), respectively. Fars and Ilam
      provinces had the highest and lowest CSR 50+ (71,381 vs. 2481), respectively. Low
      CSR (<3000) was detected in 9 provinces where 2.4 to 735.7% increase is needed to
      reach the minimum required. High CSR (>5000) was observed in 14 provinces (45.2%)
      where rates were 0.6 to 59.9% higher than the global target. Cataract surgical
      rate increased at higher economic quintiles. Differences between the first,
      second, and fifth (poorest) quintiles were statistically significant. The CSR
      concentration index was 0.1964 (95% confidence interval, 0.0964 to 0.2964).
      CONCLUSIONS: In line with the goals of the Vision 2020 initiative to eliminate
      cataract blindness, more than 70% of geographic areas in Iran have achieved the
      minimum CSR of 3000 or more. However, a large gap still exists in less than 30%
      of areas, mainly attributed to the economic status.

PMID- 25955644
TI  - Protective effects of gallic acid against spinal cord injury-induced oxidative
      stress.
AB  - The present study aimed to investigate the role of gallic acid in oxidative
      stress induced during spinal cord injury (SCI). In order to measure oxidative
      stress, the levels of lipid peroxide, protein carbonyl, reactive oxygen species
      and nitrates/nitrites were determined. In addition, the antioxidant status during
      SCI injury and the protective role of gallic acid were investigated by
      determining glutathione levels as well as the activities of catalase, superoxide
      dismutase, glutathione peroxidase and glutathione-S-transferase. Adenosine
      triphophatase (ATPase) enzyme activities were determined to evaluate the role of
      gallic acid in SCI-induced deregulation of the activity of enzymes involved in
      ion homeostasis. The levels of inflammatory markers such as nuclear factor (NF)
      kappaB and cycloxygenase (COX)-2 were determined by western blot analysis.
      Treatment with gallic acid was observed to significantly mitigate SCI-induced
      oxidative stress and the inflammatory response by reducing the oxidative stress,
      decreasing the expression of NF-kappaB and COX-2 as well as increasing the
      antioxidant status of cells. In addition, gallic acid modulated the activity of
      ATPase enzymes. Thus the present study indicated that gallic acid may have a role
      as a potent antioxidant and anti-inflammatory agent against SCI.

PMID- 25955645
TI  - Cell death pathways and phthalocyanine as an efficient agent for photodynamic
      cancer therapy.
AB  - The mechanisms of cell death can be predetermined (programmed) or not and
      categorized into apoptotic, autophagic and necrotic pathways. The process of
      Hayflick limits completes the execution of death-related mechanisms. Reactive
      oxygen species (ROS) are associated with oxidative stress and subsequent
      cytodamage by oxidizing and degrading cell components. ROS are also involved in
      immune responses, where they stabilize and activate both hypoxia-inducible
      factors and phagocytic effectors. ROS production and presence enhance cytodamage
      and photodynamic-induced cell death. Photodynamic cancer therapy (PDT) uses non
      toxic chemotherapeutic agents, photosensitizer (PS), to initiate a light
      dependent and ROS-related cell death. Phthalocyanines (PCs) are third generation
      and stable PSs with improved photochemical abilities. They are effective inducers
      of cell death in various neoplastic models. The metallated PCs localize in
      critical cellular organelles and are better inducers of cell death than other
      previous generation PSs as they favor mainly apoptotic cell death events. 

PMID- 25955646
TI  - The Drosophila retinoblastoma binding protein 6 family member has two isoforms
      and is potentially involved in embryonic patterning.
AB  - The human retinoblastoma binding protein 6 (RBBP6) is implicated in esophageal,
      lung, hepatocellular and colon cancers. Furthermore, RBBP6 was identified as a
      strong marker for colon cancer prognosis and as a predisposing factor in familial
      myeloproliferative neoplasms. Functionally, the mammalian protein interacts with
      p53 and enhances the activity of Mdm2, the prototypical negative regulator of
      p53. However, since RBBP6 (known as PACT in mice) exists in multiple isoforms and
      pact-/- mice exhibit a more severe phenotype than mdm2-/- mutants, it must
      possess some Mdm2-independent functions. The function of the invertebrate
      homologue is poorly understood. This is complicated by the absence of the Mdm2
      gene in both Drosophila and Caenorhabditis elegans. We have experimentally
      identified the promoter region of Snama, the Drosophila homologue, analyzed
      potential transcription factor binding sites and confirmed the existence of an
      additional isoform. Using band shift and co-immunoprecipitation assays combined
      with mass spectrometry, we found evidence that this gene may be regulated by,
      amongst others, DREF, which regulates hundreds of genes related to cell
      proliferation. The potential transcription factors for Snama fall into distinct
      functional groups, including anteroposterior embryonic patterning and nucleic
      acid metabolism. Significantly, previous work in mice shows that pact-/- induces
      an anteroposterior phenotype in embryos when rescued by simultaneous deletion of
      p53. Taken together, these observations indicate the significance of RBBP6
      proteins in carcinogenesis and in developmental defects. 

PMID- 25955647
TI  - Mechanism of Action of IL-7 and Its Potential Applications and Limitations in
      Cancer Immunotherapy.
AB  - Interleukin-7 (IL-7) is a non-hematopoietic cell-derived cytokine with a central
      role in the adaptive immune system. It promotes lymphocyte development in the
      thymus and maintains survival of naive and memory T cell homeostasis in the
      periphery. Moreover, it is important for the organogenesis of lymph nodes (LN)
      and for the maintenance of activated T cells recruited into the secondary
      lymphoid organs (SLOs). The immune capacity of cancer patients is suppressed that
      is characterized by lower T cell counts, less effector immune cells infiltration,
      higher levels of exhausted effector cells and higher levels of immunosuppressive
      cytokines, such as transforming growth factor beta (TGF-beta). Recombinant human
      IL-7 (rhIL-7) is an ideal solution for the immune reconstitution of lymphopenia
      patients by promoting peripheral T cell expansion. Furthermore, it can antagonize
      the immunosuppressive network. In animal models, IL-7 has been proven to prolong
      the survival of tumor-bearing hosts. In this review, we will focus on the
      mechanism of action and applications of IL-7 in cancer immunotherapy and the
      potential restrictions for its usage. 

PMID- 25955648
TI  - Anti-NR2A/B Antibodies and Other Major Molecular Mechanisms in the Pathogenesis
      of Cognitive Dysfunction in Systemic Lupus Erythematosus.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease that affects
      approximately 1-45.3 per 100,000 people worldwide. Although deaths as a result of
      active and renal diseases have been substantially declining amongst SLE patients,
      disease involving the central nervous system (CNS), collectively termed
      neuropsychiatric systemic lupus erythematosus (NPSLE), remains one of the
      important causes of death in these patients. Cognitive dysfunction is one of the
      most common manifestations of NPSLE, which comprises deficits in information
      processing speed, attention and executive function, in conjunction with
      preservation of speech. Albeit a prevalent manifestation of NPSLE, the
      pathogenetic mechanisms of cognitive dysfunction remain unclear. Recent advances
      in genetic studies, molecular techniques, neuropathology, neuroimaging and
      cognitive science have gleaned valuable insights into the pathophysiology of
      lupus-related cognitive dysfunction. In recent years, a role for autoantibodies,
      molecular and cellular mechanisms in cognitive dysfunction, has been emerging,
      challenging our previous concept of the brain as an immune privileged site. This
      review will focus on the potential pathogenic factors involved in NPSLE,
      including anti-N-methyl-d-aspartate receptor subunit NR2A/B (anti-NR2A/B)
      antibodies, matrix metalloproteinase-9, neutrophil extracellular traps and pro
      inflammatory mediators. Better understanding of these mechanistic processes will
      enhance identification of new therapeutic modalities to halt the progression of
      cognitive decline in SLE patients. 

PMID- 25955649
TI  - Gene Overexpression and RNA Silencing Tools for the Genetic Manipulation of the S
      (+)-Abscisic Acid Producing Ascomycete Botrytis cinerea.
AB  - The phytopathogenic ascomycete Botrytis cinerea produces several secondary
      metabolites that have biotechnical significance and has been particularly used
      for S-(+)-abscisic acid production at the industrial scale. To manipulate the
      expression levels of specific secondary metabolite biosynthetic genes of B.
      cinerea with Agrobacterium tumefaciens-mediated transformation system, two
      expression vectors (pCBh1 and pCBg1 with different selection markers) and one RNA
      silencing vector, pCBSilent1, were developed with the In-Fusion assembly method.
      Both expression vectors were highly effective in constitutively expressing eGFP,
      and pCBSilent1 effectively silenced the eGFP gene in B. cinerea. Bcaba4, a gene
      suggested to participate in ABA biosynthesis in B. cinerea, was then targeted for
      gene overexpression and RNA silencing with these reverse genetic tools. The
      overexpression of bcaba4 dramatically induced ABA formation in the B. cinerea
      wild type strain Bc-6, and the gene silencing of bcaba4 significantly reduced ABA
      production in an ABA-producing B. cinerea strain. 

PMID- 25955650
TI  - Cell adhesion and in vivo osseointegration of sandblasted/acid etched/anodized
      dental implants.
AB  - The authors describe a new type of titanium (Ti) implant as a Modi-anodized (ANO)
      Ti implant, the surface of which was treated by sandblasting, acid etching (SLA),
      and anodized techniques. The aim of the present study was to evaluate the
      adhesion of MG-63 cells to Modi-ANO surface treated Ti in vitro and to
      investigate its osseointegration characteristics in vivo. Four different types of
      Ti implants were examined, that is, machined Ti (control), SLA, anodized, and
      Modi-ANO Ti. In the cell adhesion study, Modi-ANO Ti showed higher initial MG-63
      cell adhesion and induced greater filopodia growth than other groups. In vivo
      study in a beagle model revealed the bone-to-implant contact (BIC) of Modi-ANO Ti
      (74.20%+/-10.89%) was much greater than those of machined (33.58%+/-8.63%), SLA
      (58.47%+/-12.89), or ANO Ti (59.62%+/-18.30%). In conclusion, this study
      demonstrates that Modi-ANO Ti implants produced by sandblasting, acid etching,
      and anodizing improve cell adhesion and bone ongrowth as compared with machined,
      SLA, or ANO Ti implants. These findings suggest that the application of Modi-ANO
      surface treatment could improve the osseointegration of dental implant.

PMID- 25955651
TI  - Mutant GNAQ promotes cell viability and migration of uveal melanoma cells through
      the activation of Notch signaling.
AB  - The occurrence of guanine nucleotide binding protein (G protein), q polypeptide
      (GNAQ) mutations has been found to be high in the majority of uveal melanomas.
      However, the underlying molecular mechanism of GNAQ mutations in modulating uveal
      melanoma is poorly understood. The aim of the present study was to investigate
      the role and underlying mechanism of mutant GNAQ in the regulation of cell
      viability and migration of uveal melanoma cells. Uveal melanoma cells containing
      mutant GNAQ were transfected with scrambled or GNAQ small-interfering RNA.
      Compared with the control, GNAQ knockdown markedly inhibited cell viability and
      migration. However, tumor cells without GNAQ mutations exhibited enhanced
      viability and migration following transfection with HA-GalphaqQL. Additionally,
      GNAQ knockdown significantly downregulated the expression of Jag-1 (Notch
      ligand), Notch intracellular domain and Hes-1 (Notch target gene) in uveal
      melanoma cells. Conversely, the GNAQ overexpression promoted their expression.
      Cell viability and migration induced by GNAQ was significantly inhibited
      following treatment with 5 umol/l MRK003, a Notch signaling inhibitor.
      Furthermore, the transfection of human influenza hemagglutinin A epitope (HA)
      GalphaqQL into tumor cells caused Yes-associated protein (YAP) dephosphorylation
      and nuclear translocation, which stimulated the expression of Jag-1 and Hes-1.
      Positive correlations were observed between the GNAQ and Jag-1 mRNA levels and
      between the GNAQ and Hes-1 mRNA levels. However, no positive correlation was
      observed between the GNAQ and YAP mRNA levels. The results suggested that GNAQ
      mutation induced viability and migration of uveal melanoma cells via Notch
      signaling activation, which is mediated by YAP dephosphorylation and nuclear
      translocation.

PMID- 25955654
TI  - Gelation of Oil upon Contact with Water: A Bioinspired Scheme for the Self-Repair
      of Oil Leaks from Underwater Tubes.
AB  - Molecular organogelators convert oils into gels by forming self-assembled fibrous
      networks. Here, we demonstrate that such gelation can be activated by contacting
      the oil with an immiscible solvent (water). Our gelator is dibenzylidene sorbitol
      (DBS), which forms a low-viscosity sol when added to toluene containing a small
      amount of dimethyl sulfoxide (DMSO). Upon contact with water, DMSO partitions
      into the water, activating gelation of DBS in the toluene. The gel grows from the
      oil/water interface and slowly envelops the oil phase. We have exploited this
      effect for the self-repair of oil leaks from underwater tubes. When a
      DBS/toluene/DMSO solution flows through the tube, it forms a gel selectively at
      the leak point, thereby plugging the leak and restoring flow. Our approach is
      reminiscent of wound-sealing via blood-clotting: there also, inactive gelators in
      blood are activated at the wound site into a fibrous network, thereby plugging
      the wound and restoring blood flow. 

PMID- 25955653
TI  - Nitration of beta-Lactoglobulin but Not of Ovomucoid Enhances Anaphylactic
      Responses in Food Allergic Mice.
AB  - BACKGROUND: We revealed in previous studies that nitration of food proteins
      reduces the risk of de novo sensitization in a murine food allergy model. In
      contrast, in situations with preformed specific IgE antibodies, in vitro
      experiments suggested an increased capacity of effector cell activation by
      nitrated food proteins. OBJECTIVE: The aim of this study was to investigate the
      influence of protein nitration on the effector phase of food allergy. DESIGN:
      BALB/c mice were immunized intraperitoneally (i.p.) with the milk allergen beta
      lactoglobulin (BLG) or the egg allergen ovomucoid (OVM), followed by intragastric
      (i.g.) gavages to induce a strong local inflammatory response and allergen
      specific antibodies. Subsequently, naive and allergic mice were intravenously
      (i.v.) challenged with untreated, sham-nitrated or nitrated BLG or OVM.
      Anaphylaxis was monitored by measuring core body temperature and determination of
      mouse mast cell protease-1 (mMCP-1) levels in blood. RESULTS: A significant drop
      of body temperature accompanied with significantly elevated concentrations of the
      anaphylaxis marker mMCP-1 were only observed in BLG allergic animals challenged
      with nitrated BLG and not in OVM allergic mice challenged with nitrated OVM. SDS
      PAGE and circular dichroism analysis of the differentially modified allergens
      revealed an effect of nitration on the secondary protein structure exclusively
      for BLG together with enhanced protein aggregation. CONCLUSION: Our data suggest
      that nitration affects differently the food allergens BLG and OVM. In the case of
      BLG, structural changes favored dimerization possibly explaining the increased
      anaphylactic reactivity in BLG allergic animals.

PMID- 25955656
TI  - Synergism between tramadol and parecoxib in the orofacial formalin test.
AB  - The aim of this study was to evaluate the interaction between tramadol and
      parecoxib in the orofacial formalin test. Tramadol (10, 31.6, 56, and 100 mg/kg
      ip) or parecoxib (31.6, 56, 100, and 178 mg/kg ip) were administered 10 min
      before formalin (2.5%) injection into the upper lip to characterize the dose
      response curve of each individual drug in the orofacial pain test in mice. Once
      the dose-response curve of each drug was obtained, an experimental effective dose
      50 (ED50 ) value was determined for each drug. The tramadol-parecoxib combination
      was evaluated in four different groups of animals. The isobolographic analysis
      and the interaction index were used to evaluate the nature of interaction between
      both drugs. The isobologram and the interaction index showed increased in the
      antinociceptive effect of the combination. The tramadol-parecoxib combination
      produces a synergism in the second phase of the orofacial formalin test.

PMID- 25955652
TI  - Coadministration of the Three Antigenic Leishmania infantum Poly (A) Binding
      Proteins as a DNA Vaccine Induces Protection against Leishmania major Infection
      in BALB/c Mice.
AB  - BACKGROUND: Highly conserved intracellular proteins from Leishmania have been
      described as antigens in natural and experimental infected mammals. The present
      study aimed to evaluate the antigenicity and prophylactic properties of the
      Leishmania infantum Poly (A) binding proteins (LiPABPs). METHODOLOGY/PRINCIPAL
      FINDINGS: Three different members of the LiPABP family have been described.
      Recombinant tools based on these proteins were constructed: recombinant proteins
      and DNA vaccines. The three recombinant proteins were employed for coating ELISA
      plates. Sera from human and canine patients of visceral leishmaniasis and human
      patients of mucosal leishmaniasis recognized the three LiPABPs. In addition, the
      protective efficacy of a DNA vaccine based on the combination of the three
      Leishmania PABPs has been tested in a model of progressive murine leishmaniasis:
      BALB/c mice infected with Leishmania major. The induction of a Th1-like response
      against the LiPABP family by genetic vaccination was able to down-regulate the IL
      10 predominant responses elicited by parasite LiPABPs after infection in this
      murine model. This modulation resulted in a partial protection against L. major
      infection. LiPABP vaccinated mice showed a reduction on the pathology that was
      accompanied by a decrease in parasite burdens, in antibody titers against
      Leishmania antigens and in the IL-4 and IL-10 parasite-specific mediated
      responses in comparison to control mice groups immunized with saline or with the
      non-recombinant plasmid. CONCLUSION/SIGNIFICANCE: The results presented here
      demonstrate for the first time the prophylactic properties of a new family of
      Leishmania antigenic intracellular proteins, the LiPABPs. The redirection of the
      immune response elicited against the LiPABP family (from IL-10 towards IFN-gamma
      mediated responses) by genetic vaccination was able to induce a partial
      protection against the development of the disease in a highly susceptible murine
      model of leishmaniasis.

PMID- 25955655
TI  - Cerebral activations related to writing and drawing with each hand.
AB  - BACKGROUND: Writing is a sequential motor action based on sensorimotor
      integration in visuospatial and linguistic functional domains. To test the
      hypothesis of lateralized circuitry concerning spatial and language components
      involved in such action, we employed an fMRI paradigm including writing and
      drawing with each hand. In this way, writing-related contributions of dorsal and
      ventral premotor regions in each hemisphere were assessed, together with effects
      in wider distributed circuitry. Given a right-hemisphere dominance for spatial
      action, right dorsal premotor cortex dominance was expected in left-hand writing
      while dominance of the left ventral premotor cortex was expected during right
      hand writing. METHODS: Sixteen healthy right-handed subjects were scanned during
      audition-guided writing of short sentences and simple figure drawing without
      visual feedback. Tapping with a pencil served as a basic control task for the two
      higher-order motor conditions. Activation differences were assessed with
      Statistical Parametric Mapping (SPM). RESULTS: Writing and drawing showed
      parietal-premotor and posterior inferior temporal activations in both hemispheres
      when compared to tapping. Drawing activations were rather symmetrical for each
      hand. Activations in left- and right-hand writing were left-hemisphere dominant,
      while right dorsal premotor activation only occurred in left-hand writing,
      supporting a spatial motor contribution of particularly the right hemisphere.
      Writing contrasted to drawing revealed left-sided activations in the dorsal and
      ventral premotor cortex, Broca's area, pre-Supplementary Motor Area and posterior
      middle and inferior temporal gyri, without parietal activation. DISCUSSION: The
      audition-driven postero-inferior temporal activations indicated retrieval of
      virtual visual form characteristics in writing and drawing, with additional
      activation concerning word form in the left hemisphere. Similar parietal
      processing in writing and drawing pointed at a common mechanism by which such
      visually formatted information is used for subsequent sensorimotor integration
      along a dorsal visuomotor pathway. In this, the left posterior middle temporal
      gyrus subserves phonological-orthographical conversion, dissociating dorsal
      parietal-premotor circuitry from perisylvian circuitry including Broca's area.

PMID- 25955658
TI  - Characterization and Modeling of Nonfilamentary Ta/TaOx/TiO2/Ti Analog Synaptic
      Device.
AB  - A two-terminal analog synaptic device that precisely emulates biological synaptic
      features is expected to be a critical component for future hardware-based
      neuromorphic computing. Typical synaptic devices based on filamentary resistive
      switching face severe limitations on the implementation of concurrent inhibitory
      and excitatory synapses with low conductance and state fluctuation. For
      overcoming these limitations, we propose a Ta/TaOx/TiO2/Ti device with superior
      analog synaptic features. A physical simulation based on the homogeneous
      (nonfilamentary) barrier modulation induced by oxygen ion migration accurately
      reproduces various DC and AC evolutions of synaptic states, including the spike
      timing-dependent plasticity and paired-pulse facilitation. Furthermore, a physics
      based compact model for facilitating circuit-level design is proposed on the
      basis of the general definition of memristor devices. This comprehensive
      experimental and theoretical study of the promising electronic synapse can
      facilitate realizing large-scale neuromorphic systems. 

PMID- 25955659
TI  - Low-Frequency Interlayer Breathing Modes in Few-Layer Black Phosphorus.
AB  - As a new two-dimensional layered material, black phosphorus (BP) is a very
      promising material for nanoelectronics and optoelectronics. We use Raman
      spectroscopy and first-principles theory to characterize and understand the low
      frequency (LF) interlayer breathing modes (<100 cm(-1)) in few-layer BP for the
      first time. Using a laser polarization dependence study and group theory
      analysis, the breathing modes are assigned to Ag symmetry. Compared to the high
      frequency (HF) Raman modes, the LF breathing modes are considerably more
      sensitive to interlayer coupling and, thus, their frequencies show a stronger
      dependence on the number of layers. Hence, they constitute an effective means to
      probe both the crystalline orientation and thickness of few-layer BP.
      Furthermore, the temperature dependence shows that in the temperature range -150
      to 30  degrees C, the breathing modes have a weak anharmonic behavior, in
      contrast to the HF Raman modes that exhibit strong anharmonicity. 

PMID- 25955657
TI  - PKM2 Subcellular Localization Is Involved in Oxaliplatin Resistance Acquisition
      in HT29 Human Colorectal Cancer Cell Lines.
AB  - Chemoresistance is the main cause of treatment failure in advanced colorectal
      cancer (CRC). However, molecular mechanisms underlying this phenomenon remain to
      be elucidated. In a previous work we identified low levels of PKM2 as a putative
      oxaliplatin-resistance marker in HT29 CRC cell lines and also in patients. In
      order to assess how PKM2 influences oxaliplatin response in CRC cells, we
      silenced PKM2 using specific siRNAs in HT29, SW480 and HCT116 cells. MTT test
      demonstrated that PKM2 silencing induced resistance in HT29 and SW480 cells and
      sensitivity in HCT116 cells. Same experiments in isogenic HCT116 p53 null cells
      and double silencing of p53 and PKM2 in HT29 cells failed to show an influence of
      p53. By using trypan blue stain and FITC-Annexin V/PI tests we detected that PKM2
      knockdown was associated with an increase in cell viability but not with a
      decrease in apoptosis activation in HT29 cells. Fluorescence microscopy revealed
      PKM2 nuclear translocation in response to oxaliplatin in HCT116 and HT29 cells
      but not in OXA-resistant HTOXAR3 cells. Finally, by using a qPCR Array we
      demonstrated that oxaliplatin and PKM2 silencing altered cell death gene
      expression patterns including those of BMF, which was significantly increased in
      HT29 cells in response to oxaliplatin, in a dose and time-dependent manner, but
      not in siPKM2-HT29 and HTOXAR3 cells. BMF gene silencing in HT29 cells lead to a
      decrease in oxaliplatin-induced cell death. In conclusion, our data report new
      non-glycolytic roles of PKM2 in response to genotoxic damage and proposes BMF as
      a possible target gene of PKM2 to be involved in oxaliplatin response and
      resistance in CRC cells. 

PMID- 25955660
TI  - A template-free method for stable CuO hollow microspheres fabricated from a metal
      organic framework (HKUST-1).
AB  - Uniform CuO hollow microspheres were successfully achieved from a non-uniform
      metal organic framework by using a template-free method. The process mechanism
      has been revealed to be spherical aggregation and Ostwald ripening. When tested
      in CO oxidation and heat treatment, these assembled microspheres exhibited an
      excellent catalytic performance and show a much better stability than the
      inherited hollow structure from MOFs. 

PMID- 25955661
TI  - Assessment of ventilation and indoor air pollutants in nursery and elementary
      schools in France.
AB  - The aim of this study was to characterize the relationship between Indoor Air
      Quality (IAQ) and ventilation in French classrooms. Various parameters were
      measured over one school week, including volatile organic compounds, aldehydes,
      particulate matter (PM2.5 mass concentration and number concentration), carbon
      dioxide (CO2 ), air temperature, and relative humidity in 51 classrooms at 17
      schools. The ventilation was characterized by several indicators, such as the air
      exchange rate, ventilation rate (VR), and air stuffiness index (ICONE), that are
      linked to indoor CO2 concentration. The influences of the season (heating or non
      heating), type of school (nursery or elementary), and ventilation on the IAQ were
      studied. Based on the minimum value of 4.2 l/s per person required by the French
      legislation for mechanically ventilated classrooms, 91% of the classrooms had
      insufficient ventilation. The VR was significantly higher in mechanically
      ventilated classrooms compared with naturally ventilated rooms. The correlations
      between IAQ and ventilation vary according to the location of the primary source
      of each pollutant (outdoor vs. indoor), and for an indoor source, whether it is
      associated with occupant activity or continuous emission.

PMID- 25955662
TI  - Neonatal screening for alpha-thalassemia by cord hemoglobin Barts: how effective
      is it?
AB  - INTRODUCTION: It has long been recognized that the hemoglobin (Hb) Bart's in cord
      blood is an accurate indicator of alpha-thalassemia and that the level of Hb
      Bart's was increased accordingly with the increasing numbers of the defective
      alpha-genes. METHODS: This study used an automatic capillary electrophoresis
      system to determine the Hb Bart's levels in cord blood. Molecular analyses were
      used to detect various genotypes of alpha-thalassemia. RESULTS: Sixty-nine of the
      total 1169 newborns were found to have an increased Hb Bart's in cord blood, in
      whom the diagnosis of alpha-thalassemia was confirmed by the DNA analysis. The
      remaining 1100 newborns had no detectable Hb Bart's at birth; among these, 45
      carriers of silent alpha-thalassemia were diagnosed by DNA analysis. All the 45
      cases had only the -alpha(3.7) deletion genotype. CONCLUSION: For newborns of one
      alpha-gene mutation, especially for 3.7-kb deletion, the method based on Hb
      Bart's is inadequate and is therefore not reliable for screening.

PMID- 25955663
TI  - Revealing chemical ordering in Pt-Co nanoparticles using electronic structure
      calculations and X-ray photoelectron spectroscopy.
AB  - The high catalytic activity of Pt-Co nanoalloys in oxygen reduction and other
      reactions is usually attributed to their Pt-rich surfaces. However,
      identification of the precise near-surface structure is by no means easily
      achievable experimentally. In this work we systematically analyzed the chemical
      ordering and surface composition of PtXCo(79-X) and PtXCo(140-X) bimetallic
      nanoparticles by means of a recently developed method based on topological energy
      expressions and electronic structure calculations. Pt is found to segregate on
      the surface, especially on corner and edge sites, forming a one atomic layer
      thick skin independent of the size and composition of the nanoparticle. In turn,
      the subsurface shell of the particle is composed mostly of Co, whereas the core
      area has a mixed composition, which depends on the overall stoichiometry. The
      formation of an outer Pt shell is corroborated by thoroughly analyzed data of X
      ray photoelectron spectroscopy experiments performed with various photon energies
      on annealed Pt-Co particles prepared in vacuum by magnetron sputtering. The core
      shell structure of Pt-Co particles is calculated to be more stable than the
      respective L10 structure. The obtained topological energy expressions are shown
      to depend only very moderately on the nanoparticle size, which allowed us to
      apply them to determine the ordering in ~4 nm big PtXCo(1463-X) species. The
      presented results deepen our understanding of the intrinsic structure of Pt-Co
      nanoparticles depending on their size and composition.

PMID- 25955664
TI  - Space and time clustering of adolescents' emergency department use and post-visit
      physician care for mood disorders in Alberta, Canada: A population-based 9-year
      retrospective study.
AB  - OBJECTIVES: We used a statistical cluster detection technique to identify
      geographic areas with higher numbers of adolescents who 1) presented to an
      emergency department (ED) for a mood disorder, and 2) were without a physician
      follow-up visit for mental health within 30 days of an ED visit. METHODS: We
      conducted a population-based analysis of ED visits (n = 6,829) made by
      adolescents aged 10-17 years (n = 5,877) using administrative databases from
      Alberta, Canada (2002-2011). Statistical analyses included summaries, directly
      standardized rates (DSRs per 100,000), and the spatial scan cluster test.
      RESULTS: Sex- and age-adjusted DSRs increased by 21.8% from 2002 to 2011
      (160.2/100,000 to 195.1/100,000). Northern Alberta had consistently higher DSRs
      than other areas of the province and areas in the north, southwest and central
      parts were identified as geographical and temporal clusters with relative risks
      of 1.67, 2.78 and 1.42 respectively. Many of these areas also had higher relative
      risks for adolescents who did not have a mental health-related visit with a
      physician within 30 days of the ED visit. About 32% (n = 1,870) did not have a
      post-ED physician visit. CONCLUSION: The potential clusters identified may
      represent geographic areas with higher disease severity or more acute care sought
      because of less availability of other services. The clusters are not all likely
      to have occurred by chance and further investigations and discussions with local
      health care policy makers about reducing the number of ED visits for mood
      disorders and increasing physician follow-up after the ED visit is an important
      next step.

PMID- 25955667
TI  - Demographic and behavioural characteristics predict bacterial STI reinfection and
      coinfection among a cross-sectional sample of laboratory-confirmed gonorrhea
      cases in a local health region from Saskatchewan, Canada.
AB  - OBJECTIVES: We aimed to identify demographic and behavioural determinants
      associated with risk of repeat STI infection and coinfection with gonorrhea and
      chlamydia in the Regina Qu'Appelle Health Region, Saskatchewan. METHODS: We
      extracted data from a cross-sectional sample of laboratory confirmed gonorrhea
      cases between 2003 and 2012 from the notifiable disease files of the Regina
      Qu'Appelle Health Region. Risk factors for repeater status were examined using
      logistic regression and for coinfection with gonorrhea and chlamydia using mixed
      effects logistic regression to account for multiple diagnoses for individual
      clients. RESULTS: Data from 1,143 cases (representing 1,027 unique individuals)
      and 1,524 reported contacts (representing 1,383 unique individuals) were
      extracted from the 10-year period. Factors associated with repeat infection
      entries in the database included younger age at first visit (p = 0.01),
      coinfection (p = 0.01), and sex trade involvement (p < 0.01). Factors associated
      with coinfection at the time of diagnosis included younger age at diagnosis (p <
      0.001) and reported alcohol or drug abuse (p = 0.04). CONCLUSION: In one of the
      first epidemiologic studies on gonorrhea in Saskatchewan, we have identified age,
      engagement in the sex trade, and drug and alcohol abuse as potential markers to
      identify clients with a high risk of reinfection and coinfection in the Regina
      Qu'Appelle Health Region. This information can help health care professionals in
      Saskatchewan's urban centres personalize their approach to counselling and
      treatment to optimize patient outcomes and disease control efforts, including
      potentially using expedited partner therapy and/or dual therapy where indicated.

PMID- 25955665
TI  - Individual and jurisdictional factors associated with voluntary HIV testing in
      Canada: Results of a national survey, 2011.
AB  - OBJECTIVE: HIV testing remains a central strategy for HIV prevention for its
      ability to link those who test positive to treatment and support. In Canada,
      national guidelines have recently changed as part of standard primary care to
      recommend voluntary HIV testing for those aged 16-64 years. Using results from a
      nationally representative survey, we examined individual and jurisdictional
      factors associated with voluntary testing. METHODS: A total of 2,139 participants
      were sampled using a regionally stratified, two-stage recruitment process.
      English or French interviews (by phone or online) were conducted during May 2011.
      Voluntary testing was defined as testing at least once for reasons other than
      blood donation, insurance purposes, immigration screening or research
      participation. Weighted logistic regression analysis (including socio
      demographic, sexual activity, HIV/AIDS knowledge and jurisdictional factors of
      HIV prevalence and anonymous testing availability) were conducted for the overall
      sample, and stratified by sex. RESULTS: Twenty-nine percent (29%) of survey
      participants reported at least one lifetime voluntary HIV test. For the full
      sample model, the following were associated with increased odds of testing: age
      <60 years, female sex, sexual minority status, perceived HIV knowledge, casual
      sex partner in previous year, and living in a higher-prevalence jurisdiction. For
      men, the strongest factor related to testing was sexual minority status (OR =
      5.15, p < 0.001); for women, it was having a casual sex partner in the previous
      year (OR = 2.57, p = 0.001). For both men and women, residing in a jurisdiction
      with lower HIV prevalence decreased odds of testing. DISCUSSION: Sex differences
      should be considered when designing interventions to increase testing uptake.
      Jurisdictional factors, including HIV prevalence and testing modality, should be
      investigated further.

PMID- 25955668
TI  - Community- and individual-level factors associated with smoking and heavy
      drinking among Aboriginal people in Canada.
AB  - OBJECTIVES: 1) To examine the association between place of residence (i.e., on-
      versus off-communities and between provinces) and daily smoking and heavy
      drinking among Aboriginal people in Canada; and 2) to identify community- and
      individual-level factors that may account for these associations. METHODS: Data
      were from the Aboriginal Peoples Survey (2001). The sample included 52,110
      Aboriginal people (>= 15 years of age). Community-level variables included: place
      of residence, community socio-economic status (SES) and perceived community
      social problems. Individual-level variables included: age, sex, education,
      income, employment status, marital status, Aboriginal heritage and social
      support. Multilevel logistic regressions were conducted to analyze the data.
      RESULTS: Living in First Nations communities (compared with living off
      communities) was associated with daily smoking, and this association was
      accounted for by perceived community social problems. However, the association
      between Inuit communities and daily smoking remained after controlling for all
      covariates (odds ratio (OR) = 1.97, 95% confidence intervals (CI) = 1.44-2.70).
      Residence in First Nations communities was associated with heavy drinking (OR =
      1.54, 95% CI = 1.17-2.04), however this risk became evident only after
      controlling for community SES, which was also positively associated with heavy
      drinking (OR = 1.46, 95% CI = 1.26-1.69). Compared with Saskatchewan, Aboriginal
      people in Atlantic Provinces (OR = 2.80, 95% CI = 2.08-3.78) or Territories (OR =
      1.39, 95% CI = 1.01-1.92) were more likely to engage in heavy drinking.
      CONCLUSION: Studies are needed to better understand the increased risk for
      smoking in Inuit communities and heavy drinking in First Nations communities,
      Atlantic Provinces and Territories, and to identify possible reasons for the
      positive association between community SES and heavy drinking among Aboriginal
      people.

PMID- 25955669
TI  - Correlates of physical activity in First Nations youth residing in First Nations
      and northern communities in Canada.
AB  - OBJECTIVES: Physical activity (PA) can help youth achieve balance among physical,
      mental, emotional and spiritual dimensions of health. The objective was to
      identify individual, family and community factors associated with PA among First
      Nations (FN) youth residing in on-reserve and northern FN communities. METHODS:
      Participants were 4,837 youth (12-17 years of age) responding to the 2008/10
      First Nations Regional Health Survey. Through in-person interviews, youth
      responded to questions about moderate-to-vigorous physical activity (MVPA),
      participation in traditional physical activities, and individuallevel, family and
      community factors. RESULTS: When averaged across all days of the year, 65% of FN
      youth accumulated at least 60 min/day of MVPA and 48% of youth participated in at
      least one traditional FN PA in the previous year. Being male, having a lower
      number of chronic conditions, living in balance physically, living with at least
      one biological parent, having more relatives help youth understand their culture,
      having more community challenges and having more leisure/recreation facilities
      were independently associated with an increased likelihood of accumulating >= 60
      min of MVPA. Younger age, being male, knowledge and use of FN language, living in
      balance spiritually, living with at least one biological parent, having more
      relatives help youth understand their culture, living in a community of <= 300
      people, and perceiving the natural environment and community health programs as
      strengths were independently associated with participation in traditional FN
      physical activities. CONCLUSION: There are several correlates of PA from diverse
      ecological levels among FN youth.

PMID- 25955670
TI  - The association between the interpregnancy interval and autism spectrum disorder
      in a Canadian cohort.
AB  - OBJECTIVES: Two studies reported an increased risk of autistic disorder in
      children conceived less than 12 months after a previous birth. Our objective was
      to examine the association between the interpregnancy interval (IPI) and autism
      spectrum disorder (ASD) in a Canadian cohort. METHODS: Using administrative
      datasets housed at the Manitoba Centre for Health Policy, we identified pairs of
      first- and second-born singleton siblings born between 1988 and 2005. Diagnoses
      of ASD were ascertained by searching physician billing claims, hospital discharge
      abstracts, education data, and a database containing information on individuals
      identified for a 2002-2007 ASD surveillance program in Manitoba. Logistic
      regression models were fit to examine the association between the IPI and ASD in
      41,050 second-born siblings where the first-borns did not have ASD, using IPIs of
      >= 36 months as the reference category and specifying three case groups. Case
      Group 1 included individuals with at least one ASD code (n = 490); Case Group 2
      included those with two or more ASD codes (n = 375); and Case Group 3 comprised
      individuals with a record in the ASD surveillance program database (n = 141).
      RESULTS: The adjusted odds ratios (ORs) for IPIs shorter than 12 months ranged
      from 1.22 (95% CI: 0.91-1.63) for Case Group 1 to 1.72 (95% CI: 0.96-3.06) for
      Case Group 3. When the case groups were restricted to individuals with more
      severe ASD, the ORs increased and were significant for Case Groups 1 and 2.
      CONCLUSION: Our findings also support an association between short IPIs and more
      severe ASD.

PMID- 25955671
TI  - The impact of school policies and practices on students' diets, physical activity
      levels and body weights: A province-wide practice-based evaluation.
AB  - OBJECTIVES: To assess what health promotion policies and practices were adopted
      by schools in Nova Scotia and the extent that these policies and practices
      affected the diet quality, physical activity (PA) and weight status of students.
      METHODS: We developed and administered a 'school practice assessment tool' to
      assess the presence of 72 different school-based health promotion policies and
      practices. Surveys were conducted in 2003 and 2011 to assess diet, PA and weight
      status in approximately 10,000 grade 5 students. We used multilevel regression
      methods to examine changes in these outcomes across schools with varying levels
      of health promotion policies and practices between the two time-points. RESULTS:
      Between 2003 and 2011 the diet quality of students improved, PA decreased and the
      prevalence of childhood obesity increased. Although we did not find consistent or
      significant favourable benefits resulting from higher implementation levels, we
      did observe fewer negative trends among schools at higher levels of
      implementation. CONCLUSION: Our results build on the current gap in knowledge on
      the impact of Health Promoting Schools (HPS) implementation through population
      health interventions, but there is a continued need for further evaluation and
      monitoring of school policies to understand how HPS practices are supporting
      healthier eating and PA for students.

PMID- 25955672
TI  - Fast food intake in Canada: Differences among Canadians with diverse demographic,
      socio-economic and lifestyle characteristics.
AB  - OBJECTIVES: To estimate the contribution of fast food to daily energy intake, and
      compare intake among Canadians with varied demographic, socioeconomic and
      lifestyle characteristics. METHODS: Using the National Cancer Institute method,
      nationally representative estimates of mean usual daily caloric intake from fast
      food were derived from 24-hour dietary recall data from the Canadian Community
      Health Survey Cycle 2.2 (n = 17,509) among participants age >= 2 years. Mean
      daily intake and relative proportion of calories derived from fast food were
      compared among respondents with diverse demographic (age, sex, provincial and
      rural/urban residence), socio-economic (income, education, food security status)
      and health and lifestyle characteristics (physical activity, fruit/vegetable
      intake, vitamin/ mineral supplement use, smoking, binge drinking, body mass index
      (BMI), self-rated health and dietary quality). RESULTS: On average, Canadians
      reported consuming 146 kcal/day from fast food, contributing to 6.3% of usual
      energy intake. Intake was highest among male teenagers (248 kcal) and lowest
      among women >= 70 years of age (32 kcal). Fast food consumption was significantly
      higher among respondents who reported lower fruit and vegetable intake, poorer
      dietary quality, binge drinking, not taking vitamin/mineral supplements (adults
      only), and persons with higher BMI. Socio-economic status, physical activity,
      smoking and self-rated health were not significantly associated with fast food
      intake. CONCLUSION: While average Canadian fast food consumption is lower than
      national US estimates, intake was associated with lower dietary quality and
      higher BMI. Findings suggest that research and intervention strategies should
      focus on dietary practices of children and adolescents, whose fast food intakes
      are among the highest in Canada.

PMID- 25955673
TI  - Tridimensionality of alcohol use in Canada: Patterns of drinking, contexts and
      motivations to drink in the definition of Canadian drinking profiles according to
      gender.
AB  - OBJECTIVES: The aim of this paper is to examine whether there is an underlying
      multidimensional typology of drinking according to gender among a population
      presenting heterogeneous drinking profiles in Canada. METHODS: Latent class
      analysis was chosen to analyze the degree of statistical relationship among three
      indicators of drinking practices: patterns of drinking - i.e., frequency and
      quantity; contexts; and motivations to drink. Multivariate multilogistic
      regressions were conducted to explore the composition of each typology by age and
      education. Participants were selected from the Canadian GENACIS survey (Gender,
      Alcohol, and Culture: An International Study) and comprised 871 men and 843 women
      (N = 1,714) aged between 18 and 77 years and being regular alcohol drinkers
      (consumption at least once a month). Respondents to the GENACIS questionnaire
      completed questions on use, contexts and reasons to drink as well as socio
      economic questions (age and education), adjusted by Canadian province of
      residence. RESULTS: Six profiles were distinguished among men and five among
      women. Men and women share four drinking patterns but present distinctive
      characteristics of drinking. We also observed variability in the relationship
      according to socio-economic status and gender. CONCLUSION: Our results confirmed
      the complexity and variability of drinking practices according to gender in
      Canada and the necessity to focus on gender and social dimensions in order to
      enhance our understanding of alcohol use. This study also reinforces the idea of
      adapting promotion strategies and interventions in public health by gender and
      social status in order to make them more efficient.

PMID- 25955674
TI  - Development of a measure of health care affordability applicable in a publicly
      funded universal health care system.
AB  - OBJECTIVE: Direct measures of health care affordability from the user perspective
      are needed to monitor equitable access to publicly funded health care in Canada.
      The objective of our study was to develop a survey-based measure of healthcare
      affordability applicable to the Canadian context. METHODS: We developed items
      after focus group exploration of access and cost barriers in the healthcare
      trajectory. We administered an initial instrument by telephone to a randomly
      selected sample of 750 respondents in metropolitan, rural, and remote settings in
      Quebec. After analysis we developed a new, self-administered version eliciting
      the frequency of problem access due to five affordability dimensions. This
      version was mailed to a subset of participants. We conducted exploratory and
      confirmatory factor analysis. We used ordinal logistic regression modelling to
      examine how individual items and the subscale score predicted indicators of
      difficult access. We looked for effect modification by income categories.
      RESULTS: The five items load on a single construct with good internal consistency
      (alpha = 0.77). The overall score, 0 to 5, reflects the sum of problems with
      healthcare affordability due to direct and indirect costs. The item and subscale
      scores are sensitive to income status, with affordability problems more prevalent
      among low-income than high-income respondents. Each unit increase in the subscale
      score predicts increased likelihood of unmet needs (OR = 1.54), emergency room
      use (OR = 1.41), and health problem aggravation (OR = 1.80). DISCUSSION: This
      subscale reliably and validly measures cost barriers to medically necessary
      services in Canada, and can potentially be applied in other settings with
      publicly funded health systems. It can be used to monitor and compare healthcare
      equity.

PMID- 25955675
TI  - A scoping review of mental health issues and concerns among immigrant and refugee
      youth in Canada: Looking back, moving forward.
AB  - BACKGROUND: Youth comprise a significant portion of the total immigrant
      population in Canada. Immigrant and refugee youth often have different migration
      trajectories and experiences, which can result in different mental health
      outcomes. Research is emerging in this area, but study findings have not yet been
      consolidated. RESEARCH QUESTION: What is known from the existing literature about
      mental health issues and concerns among immigrant and refugee youth in Canada?
      METHOD: We searched Embase, Health Star, Medline, CINAHL, PsycINFO, and Social
      Science Abstracts databases for the period 1990-2013 for Canadian studies related
      to the mental health of youth born outside Canada. Seventeen studies met
      inclusion criteria. RESULTS: Determinants of mental illness included pre
      migration experiences, number of years since immigration to Canada, post
      migration family and school environment, in- and out-group problems,
      discrimination, and lack of equitable access to health care. Only a few common
      categories of mental illness were identified, and the burden of mental illness
      was shared differently across gender and immigration status, with female youth
      experiencing more mental health problems than male youth. Some studies identified
      fewer emotional and behavioural problems among refugee youth; others reported
      higher rates of psychopathology among refugee youth compared with their Canadian
      born provincial counterparts. Pre-migration experiences and the kinds of trauma
      experienced were important for refugee youth's mental health. Findings also
      indicated the importance of family involvement, school settings as points of care
      and services, and in terms of timing, focusing on the first year of arrival in
      Canada. PRACTICE IMPLICATIONS: Professionals must work across health, social, and
      settlement sectors to address the various pre- and post-migration determinants of
      mental health and illness, and provide more timely and effective services based
      on how and when these determinants affect different groups of youth.

PMID- 25955676
TI  - The ineffectiveness and unintended consequences of the public health war on
      obesity.
AB  - The public health war on obesity has had little impact on obesity prevalence and
      has resulted in unintended consequences. Its ineffectiveness has been attributed
      to: 1) heavy focus on individual-based approaches and lack of scaled-up socio
      environmental policies and programs, 2) modest effects of interventions in
      reducing and preventing obesity at the population level, and 3) inappropriate
      focus on weight rather than health. An unintended consequence of these policies
      and programs is excessive weight preoccupation among the population, which can
      lead to stigma, body dissatisfaction, dieting, disordered eating, and even death
      from effects of extreme dieting, anorexia, and obesity surgery complications, or
      from suicide that results from weight-based bullying. Future public health
      approaches should: a) avoid simplistic obesity messages that focus solely on
      individuals' responsibility for weight and health, b) focus on health outcomes
      rather than weight control, and c) address the complexity of obesity and target
      both individual-level and system-level determinants of health.

PMID- 25955677
TI  - Linking missing data to study outcomes using multiple imputations.

PMID- 25955678
TI  - Re: "Linking missing data to study outcomes using multiple imputations".

PMID- 25955679
TI  - Ebola viral disease: Need for augmented "One Health" approaches in Africa.

PMID- 25955680
TI  - Errata.

PMID- 25955681
TI  - An insertion/deletion polymorphism at miRNA-122 binding site in the IL1A is
      associated with a reduced risk of cervical squamous cell carcinoma.
AB  - OBJECTIVE: Previous studies have shown that miRNA plays a key role in cervical
      carcinogenesis. Interleukin (IL)-1alpha can promote tumor growth, invasion,
      migration, and angiogenesis. An insertion/deletion polymorphism (rs3783553) in
      the IL1A 3' untranslated region may disrupt a binding site for miR-122 and miR
      378 and thus change the transcription of IL-1alpha. The purpose of this study was
      to evaluate the association between the rs3783553 polymorphism and the risk of
      cervical squamous cell carcinoma (CSCC). METHODS: Polymerase chain reaction was
      used to genotype the IL1A rs3783553 polymorphism in 235 patients with CSCC and
      326 controls. RESULTS: We found that the ins/ins genotype had a decreased risk to
      develop CSCC (odds ratio [OR]=0.48, 95% confidence interval [CI], 0.25-0.95).
      However, no significant association was observed between the IL1A rs3783553
      genotype and clinical features. CONCLUSION: These findings indicate that the IL1A
      rs3783553 polymorphism may be associated with the etiology of CSCC.

PMID- 25955682
TI  - Pediatric palliative care in the community.
AB  - Early integration of pediatric palliative care (PPC) for children with life
      threatening conditions and their families enhances the provision of holistic
      care, addressing psychological, social, spiritual, and physical concerns, without
      precluding treatment with the goal of cure. PPC involvement ideally extends
      throughout the illness trajectory to improve continuity of care for patients and
      families. Although current PPC models focus primarily on the hospital setting,
      community-based PPC (CBPPC) programs are increasingly integral to the
      coordination, continuity, and provision of quality care. In this review, the
      authors examine the purpose, design, and infrastructure of CBPPC in the United
      States, highlighting eligibility criteria, optimal referral models to enhance
      early involvement, and fundamental tenets of CBPPC. This article also appraises
      the role of CBPPC in promoting family-centered care. This model strives to
      enhance shared decision making, facilitate seamless handoffs of care, maintain
      desired locations of care, and ease the end of life for children who die at home.
      The effect of legislation on the advent and evolution of CBPPC also is discussed,
      as is an assessment of the current status of state-specific CBPPC programs and
      barriers to implementation of CBPPC. Finally, strategies and resources for
      designing, implementing, and maintaining quality standards in CBPPC programs are
      reviewed.

PMID- 25955683
TI  - Inter-laboratory evaluation of SNP-based forensic identification by massively
      parallel sequencing using the Ion PGMTM.
AB  - Next generation sequencing (NGS) offers the opportunity to analyse forensic DNA
      samples and obtain massively parallel coverage of targeted short sequences with
      the variants they carry. We evaluated the levels of sequence coverage, genotyping
      precision, sensitivity and mixed DNA patterns of a prototype version of the first
      commercial forensic NGS kit: the HID-Ion AmpliSeqTM Identity Panel with 169
      markers designed for the Ion PGMTM system. Evaluations were made between three
      laboratories following closely matched Ion PGMTM protocols and a simple
      validation framework of shared DNA controls. The sequence coverage obtained was
      extensive for the bulk of SNPs targeted by the HID-Ion AmpliSeqTM Identity Panel.
      Sensitivity studies showed 90-95% of SNP genotypes could be obtained from 25 to
      100pg of input DNA. Genotyping concordance tests included Coriell cell-line
      control DNA analyses checked against whole-genome sequencing data from 1000
      Genomes and Complete Genomics, indicating a very high concordance rate of 99.8%.
      Discordant genotypes detected in rs1979255, rs1004357, rs938283, rs2032597 and
      rs2399332 indicate these loci should be excluded from the panel. Therefore, the
      HID-Ion AmpliSeqTM Identity Panel and Ion PGMTM system provide a sensitive and
      accurate forensic SNP genotyping assay. However, low-level DNA produced much more
      varied sequence coverage and in forensic use the Ion PGMTM system will require
      careful calibration of the total samples loaded per chip to preserve the
      genotyping reliability seen in routine forensic DNA. Furthermore, assessments of
      mixed DNA indicate the user's control of sequence analysis parameter settings is
      necessary to ensure mixtures are detected robustly. Given the sensitivity of Ion
      PGMTM, this aspect of forensic genotyping requires further optimisation before
      massively parallel sequencing is applied to routine casework. 

PMID- 25955684
TI  - Conformational landscape and the selectivity of cytochrome P450cam.
AB  - Conformational heterogeneity and dynamics likely contribute to the remarkable
      activity of enzymes but are challenging to characterize experimentally. These
      features are of particular interest within the cytochrome P450 class of
      monooxygenases, which are of great academic, medicinal, and biotechnological
      interest as they recognize a broad range of substrates, such as various lipids,
      steroid precursors, and xenobiotics, including therapeutics. Here, we use linear
      and 2D IR spectroscopy to characterize the prototypical P450, cytochrome P450cam,
      bound to three different substrates, camphor, norcamphor, or thiocamphor, which
      are hydroxylated with high, low, and intermediate regioselectivity, respectively.
      The data suggest that specific interactions with the substrate drive the
      population of two different conformations, one that is associated with high
      regioselectivity and another associated with lower regioselectivity. Although Y96
      mediates a hydrogen bond thought necessary to orient the substrate for high
      regioselectivity, the population and dynamics of the conformational states are
      largely unaltered by the Y96F mutation. This study suggests that knowledge of the
      conformational landscape is central to understanding P450 activity, which has
      important practical ramifications for the design of therapeutics with optimized
      pharmacokinetics, and the manipulation of P450s, and possibly other enzymes, for
      biotechnological applications. 

PMID- 25955685
TI  - miR-206 inhibits metastasis-relevant traits by degrading MRTF-A in anaplastic
      thyroid cancer.
AB  - Thyroid cancer develops from follicular or parafollicular thyroid cells. A higher
      proportion of anaplastic thyroid cancer has an adverse prognosis. New drugs are
      being used in clinical treatment. However, for advanced thyroid malignant
      neoplasm such as anaplastic thyroid carcinoma, the major impediment to successful
      control of the disease is the absence of effective therapies. Elucidating
      molecular mechanism of the disease will help us to further understand the
      pathogenesis and progression of the disease and offer new targets for effective
      therapies. In this study, we found that MRTF-A expression was upregulated in
      metastatic anaplastic thyroid cancer tissues, compared with primary cancer
      tissues and it promoted metastasis-relevant traits in vitro. miR-206 was
      negatively associated with metastasis in anaplastic cancer and it degraded MRTF-A
      by targeting its 3'-UTR in ARO anaplastic thyroid cancer cells. In addition, miR
      206 overexpression inhibited invasion and migration and silencing miR-206
      promoted migration and invasion in the cells. Important, restoration of MRTF-A
      could abrogate miR-206-mediated migration and invasion regulation. Thus, we
      concluded that miR-206 inhibited invasion and metastasis by degrading MRTF-A in
      anaplastic thyroid cancer. 

PMID- 25955686
TI  - meso-Aryl [28]Hexaphyrin Silicon Complexes Bearing Various Si-Substituents and
      1,16-Dihydrohexaphyrin bis-Chlorosilicon Complex.
AB  - Herein, the synthesis of Mobius aromatic [28]hexaphyrin silicon complexes bearing
      various Si-substituents from reactions of [28]hexaphyrin 1 with suitable silicon
      sources in the presence of a base is reported. Si-substituents newly introduced
      are vinyl (4), phenyl (6), hydroxy (7), and hydride groups (8). X-ray
      crystallographic analysis of complexes 6 and 7 has shown trigonal bipyramidal
      penta-coordinated silicon atoms, which are favorable for the hexaphyrin ligands
      to take on smoothly twisted Mobius conformations. N-fused Si-vinyl complex 5 was
      also isolated and structurally well characterized. Through these studies, the Si
      substituent effect has been shown to be relatively small. Reaction of 1 with
      HSiCl3 in CH2Cl2 gave 1,16-dihydrohexaphyrin bis-chlorosilicon complex 9,
      probably through intramolecular hydride transfer from the silane to the pyrrolic
      alpha-carbon.

PMID- 25955687
TI  - Contrasting Sleeve Gastrectomy with Lifestyle Modification Therapy in the
      Treatment of Polycystic Ovary Syndrome.
AB  - AIMS: To explore the feasibility of sleeve gastrectomy (SG) as a treatment for
      polycystic ovary syndrome (PCOS) and its potential to improve clinical efficacy
      in PCOS patients with symptoms of oligomenorrhea. PATIENTS AND METHODS: Twenty
      four obese patients with PCOS underwent laparoscopic SG. Simultaneously, 24 obese
      patients with PCOS received lifestyle modification therapy (LMT). Follow-ups were
      conducted at 3-6 months. Weight loss, menstruation, and improvements in hirsutism
      and metabolic symptoms were compared. RESULTS: In the SG group, 20 patients were
      restored to normal menstrual cycles and ovulation at 3-6 months after surgery.
      Their average androgen levels decreased significantly following surgery (P=.012).
      Conversely, only 6 patients in the LMT group were restored to normal menstrual
      cycles and ovulation after receiving 3 months of treatment. Their average
      preoperative and postoperative androgen levels showed a nonstatistically
      significant decrease (P>.05). Compared with the LMT group, the SG group showed
      more pronounced improvements in menstruation. Additionally, body mass and body
      mass index were significantly reduced in patients in the SG group 3 months after
      the surgeries, with maximum weight loss observed at approximately 6 months after
      surgery. Patients who received LMT showed a gradual weight reduction such that
      body mass decreased significantly after 3 months (P<. 001). Compared with
      patients in the LMT group, patients in the SG group showed greater weight loss
      results (P<.0001). CONCLUSIONS: In patients with PCOS, SG resulted in more marked
      weight loss and better improvements in clinical symptoms compared with LMT.

PMID- 25955689
TI  - Downregulation of CD9 promotes pancreatic cancer growth and metastasis through
      upregulation of epidermal growth factor on the cell surface.
AB  - The expression of CD9 has been shown to be inversely associated with pancreatic
      cancer metastasis but the underlying mechanism remains incompletely understood.
      Using the two closely associated pancreatic cancer cell lines, PaTu-8898s and
      PaTu-8898t, which are metastatic and non-metastatic, respectively, we showed that
      the PaTu-8988s cells expressed a lower level of CD9 but had higher proliferation
      and migration rates than the PaTu-8898t cells. An inverse correlation between CD9
      expression and the cell surface level of epidermal growth factor receptor (EGFR)
      was observed in both cell lines. In the PaTu-8898s cells, overexpression of CD9
      decreased the cell surface expression of EGFR, associated with increased
      expression of dynamin-2, whereas in the PaTu-8898t cells, knockdown of CD9 with
      RNA interference (RNAi) increased the cell surface expression of EGFR, associated
      with decreased expression of dynamin-2. However, the total EGFR level did not
      change by manipulation of CD9 expression, suggesting that CD9 plays a role in
      EGFR endocytosis. Furthermore, in the PaTu-8898ts cells, CD9 overexpression
      decreased the cell proliferation and migration, which were reversed by EGFR
      overexpression, whereas in the PaTu-8898t cells, CD9 knockdown enhanced the cell
      proliferation and migration which were blocked by EGFR RNAi both in vitro and in
      vivo. Thus, in pancreatic cancer cells, downregulation of CD9 may play a role in
      cancer growth and metastasis through, at least in part, enhancing cell surface
      expression of EGFR.

PMID- 25955688
TI  - Methodologies for pre-validation of biofilters and wetlands for stormwater
      treatment.
AB  - BACKGROUND: Water Sensitive Urban Design (WSUD) systems are frequently used as
      part of a stormwater harvesting treatment trains (e.g. biofilters (bio-retentions
      and rain-gardens) and wetlands). However, validation frameworks for such systems
      do not exist, limiting their adoption for end-uses such as drinking water. The
      first stage in the validation framework is pre-validation, which prepares
      information for further validation monitoring. OBJECTIVES: A pre-validation
      roadmap, consisting of five steps, is suggested in this paper. Detailed methods
      for investigating target micropollutants in stormwater, and determining challenge
      conditions for biofilters and wetlands, are provided. METHODS: A literature
      review was undertaken to identify and quantify micropollutants in stormwater.
      MUSIC V5.1 was utilized to simulate the behaviour of the systems based on 30-year
      rainfall data in three distinct climate zones; outputs were evaluated to identify
      the threshold of operational variables, including length of dry periods (LDPs)
      and volume of water treated per event. RESULTS: The paper highlights that a
      number of micropollutants were found in stormwater at levels above various
      worldwide drinking water guidelines (eight pesticides, benzene, benzo(a)pyrene,
      pentachlorophenol, di-(2-ethylhexyl)-phthalate and a total of polychlorinated
      biphenyls). The 95th percentile LDPs was exponentially related to system design
      area while the 5th percentile length of dry periods remained within short
      durations (i.e. 2-8 hours). 95th percentile volume of water treated per event was
      exponentially related to system design area as a percentage of an impervious
      catchment area. CONCLUSIONS: The out-comings of this study show that pre
      validation could be completed through a roadmap consisting of a series of steps;
      this will help in the validation of stormwater treatment systems.

PMID- 25955690
TI  - Differences in the protein expression levels of Trx2 and Prx3 in the hippocampal
      CA1 region between adult and aged gerbils following transient global cerebral
      ischemia.
AB  - The thioredoxin (Trx) and peroxiredoxin (Prx) redox system is associated with
      neuronal damage and neuroprotective effects via the regulation of oxidative
      stress in brain ischemia. In the present study, ischemia-induced changes in the
      protein expression levels of Trx2 and Prx3 in the stratum pyramidale (SP) of the
      hippocampal CA1 region were investigated in adult and aged gerbils, subjected to
      5 min of transient global cerebral ischemia, using immunohistochemistry and
      western blot analysis. In the adult ischemia-group, minimal Trx2 immunoreactivity
      was detected in the SP 2 days after ischemia-reperfusion. In the aged animals,
      the Trx2 immunoreactivity in the sham-group was marginally lower compared with
      that in the adult sham-group. In the aged ischemia-group, Trx2 immunoreactivity
      in the SP was significantly higher 1, 2 and 4 days post-ischemia, compared with
      that in the adult ischemia-group and, in the 5 days post-ischemia group, Trx2
      immunoreactivity was significantly decreased in the SP. Prx3 immunoreactivity in
      the SP of the adult ischemia-group was significantly decreased from 4 days after
      ischemia-reperfusion. In the aged animals, Prx3 immunoreactivity in the sham
      group was also marginally lower compared with that in the adult sham-group. Prx3
      immunoreactivity in the aged ischemia-group was also significantly higher 1, 2
      and 4 days post-ischemia, compared with the adult ischemia-group; however, the
      Prx3 immunoreactivity was significantly decreased 5 days post-ischemia. The
      western blot analyses revealed that the pattern of changes in the protein levels
      of Trx2 and Prx3 in the adult and aged hippocampal CA1 region following ischemic
      damage were similar to the results obtained in the immunohistochemical data.
      These findings indicated that cerebral ischemia lead to different protein
      expression levels of Trx2 and Prx3 in the hippocampal CA1 region between adult
      and aged gerbils, and these differences may be associated with more delayed
      neuronal death in the aged gerbil hippocampus following transient global cerebral
      ischemia.

PMID- 25955691
TI  - A hyposensitive anticancer drug induces higher surface expression and release of
      heat shock proteins in a human hepatocellular carcinoma cell line.
AB  - Heat shock proteins (HSPs) respond to multiple stresses and have been implicated
      as essential immune chaperones that regulate innate and adaptive immunity. The
      exposure of HSPs containing tumour peptide complex to immune surveillance
      elements may elicit a specific anti-tumour response. The present study examined
      the potential of anticancer drugs to induce apoptosis of HepG2 cells and elicit
      the expression of HSP proteins, including HSP70 and gp96, on the membrane or
      their release to the extracellular environment, leading to HSP exposure. In the
      present study, etoposide and carboplatin were classified by an adenosine
      triphosphate assay as representatives of hypersensitive and hyposensitive
      anticancer drugs, respectively. Flow cytometry, immunofluorescence, ELIZA and
      reverse transcription quantitative polymerase chain reaction were all used to
      detect changes in the HSPs. The results demonstrated that etoposide and
      carboplatin induced apoptosis of HepG2 cells. In addition, following treatment
      with etoposide or carboplatin, HSP70/gp96 expression increased, demonstrating a
      'transfer expression' pattern: The cytosol expression decreased while the surface
      expression increased. These alterations progressed steadily with notable
      alterations following treatment with etoposide for 24 h or carboplatin for 72 h.
      Additionally, at the end of treatment, release of HSP70/gp96 to the extracellular
      environment increased. Notably, following treatment with the hyposensitive
      anticancer drug carboplatin for 72 h, the surface expression of gp96 in HepG2
      cells was significantly increased. These results suggest that when combined with
      cancer cell apoptosis, anticancer drugs induce the membrane expression and
      release of HSP70/gp96 in hepatocellular carcinoma (HCC) cells, which may
      represent a crucial event in the immune anti-tumour response. Notably, treatment
      with the hyposensitive anticancer drug for a longer time period resulted in
      greater surface expression and release of gp96, which suggests a potential use
      for hyposensitive anticancer drugs in HSP-based dendritic cell vaccine
      preparation and chemoimmunotherapy for HCC patients.

PMID- 25955692
TI  - Exposure to ambient air pollution in Canada and the risk of adult leukemia.
AB  - There is a paucity of studies investigating adult leukemia and air pollution. To
      address this gap, we analyzed data from a Canadian population-based case-control
      study conducted in 1994-1997. Cases were 1064 adults with incident leukemia and
      controls were 5039 healthy adults. We used data from satellites and fixed-site
      monitoring stations to estimate residential concentrations of NO2 and fine
      particulate matter (PM2.5) for the period prior to diagnosis, starting in 1975
      and ending in 1994. We modeled the average annual exposure of each subject. Odds
      ratios (OR) and their 95% confidence intervals (CI) were estimated using logistic
      regression, adjusted for age, gender, province, smoking, education, body mass
      index, income, and self-reported exposures to ionizing radiation and benzene. We
      found an 'n-shaped' response function between exposure to NO2 and all forms of
      leukemia: from the tenth percentile to the median (4.51 to 14.66 ppb), the OR was
      1.20; 95% CI: 0.97-1.48 and from the 75th percentile to the 90th (22.75 to 29.7
      ppb), the OR was 0.79; 95% CI 0.68-0.93. For PM2.5 we found a response function
      consistent with a linear model, with an OR per 10 MUg/m(3) of 0.97 (95% CI 0.75
      1.26). For chronic lymphocytic leukemia we found response functions that were
      consistent with a simple linear model, with an OR per 5 ppb of NO2 of 0.93 (95%
      CI 0.86-1.00) and an OR per 10 MUg/m(3) of PM2.5 of 0.62 (95% CI 0.42-0.93). In
      summary, for chronic lymphocytic leukemia we found no evidence of an association
      with air pollution and with all forms of leukemia we found weak evidence of an
      association only at low concentrations of NO2. It is possible that these
      inconsistent results may have arisen because of unaccounted urban/rural
      differences or possibly from a selection effect, especially among controls.

PMID- 25955693
TI  - Concentrations and loads of PCBs, dioxins, PAHs, PBDEs, OC pesticides and
      pyrethroids during storm and low flow conditions in a small urban semi-arid
      watershed.
AB  - Urban runoff has been identified in water quality policy documents for San
      Francisco Bay as a large and potentially controllable source of pollutants. In
      response, concentrations of suspended sediments and a range of trace organic
      pollutants were intensively measured in dry weather and storm flow runoff from a
      100% urban watershed. Flow in this highly urban watershed responded very quickly
      to rainfall and varied widely resulting in rapid changes of turbidity, suspended
      sediments and pollutant concentrations. Concentrations of each organic pollutant
      class were within similar ranges reported in other studies of urban runoff,
      however comparison was limited for several of the pollutants given information
      scarcity. Consistently among PCBs, PBDEs, and PAHs, the more hydrophobic
      congeners were transported in larger proportions during storm flows relative to
      low flows. Loads for Water Years 2007-2010 were estimated using regression with
      turbidity during the monitored months and a flow weighted mean concentration for
      unmonitored dry season months. More than 91% of the loads for every pollutant
      measured were transported during storm events, along with 87% of the total
      discharge. While this dataset fills an important local data gap for highly urban
      watersheds of San Francisco Bay, the methods, the uniqueness of the analyte list,
      and the resulting interpretations have applicability for managing pollutant loads
      in urban watersheds in other parts of the world. 

PMID- 25955694
TI  - Metal concentrations and distribution in paint waste generated during bridge
      rehabilitation in New York State.
AB  - Between 1950 and 1980, lead and chromium along with other metals have been used
      in paint coatings to protect bridges from corrosion. In New York State with 4500
      bridges in 11 Regions 2385 of the bridges have been rehabilitated and
      subsequently repainted after 1989 when commercial use of lead based paint was
      prohibited. The purpose of this research was to address the concentration and
      distribution of trace metals in the paint waste generated during bridge
      rehabilitation. Using hypothesis testing and stratified sampling theory, a
      representative sample size of 24 bridges from across the state was selected that
      resulted in 117 paint waste samples. Field portable X-ray fluorescence (FP-XRF)
      analysis revealed metal concentrations ranged from 5 to 168,090 mg kg(-1) for Pb,
      49,367 to 799,210 mg kg(-1) for Fe, and 27 to 425,510 mg kg(-1) for Zn. Eighty
      percent of the samples exhibited lead concentrations greater than 5000 mg kg(-1).
      The elevated iron concentrations may be attributed to the application of steel
      grit as an abrasive blasting material routinely used by state Departments of
      Transportation in the paint removal process. Other metals including Ba and Cr
      were observed in the paint waste as well. As a result of the paint formulation,
      metals were found to be associated in the paint waste (Pb correlated with Cr
      (r=0.85)). The elevated metal concentrations observed raises concern over the
      potential impact of leaching from this waste stream.

PMID- 25955695
TI  - Automobile windshield washer fluid: A potential source of transmission for
      Legionella.
AB  - Epidemiological evidence suggesting driving cars to be a risk factor for
      legionellosis has prompted public health studies to investigate vehicle
      windshield washer fluid as a novel transmission source of this disease. The goal
      of the current study was to investigate whether or not windshield washer fluid
      could serve as a potential source of transmission for Legionella. A wide
      variation in the survival of L. pneumophila was observed when incubated in
      different washer fluids at 25 and 37  degrees C, however, one brand tested
      supported Legionella survival similar to or greater than sterilized deionized
      water. In addition, 1 L of tap water contained in a washer fluid reservoir was
      able to support population growth and survival of Legionella for several months.
      In a field study examining the windshield washer fluid of 12 elementary school
      buses, Legionella were detected from 84% of samples at a high concentration of
      8.1*10(4) CFU/mL. Culturable cells were also detected in aerosolized washer fluid
      during washer fluid spray. By demonstrating survival in certain windshield washer
      fluids, growth within washer fluid reservoirs, and the presence of viable cells
      in bus washer fluid spray, we have provided evidence suggesting the potential for
      a novel route of Legionella exposure.

PMID- 25955696
TI  - Expression and properties of the glyoxysomal and cytosolic forms of isocitrate
      lyase in Amaranthus caudatus L.
AB  - Isocitrate lyase (EC 4.1.3.1) catalyzes the reversible conversion of d-isocitrate
      to succinate and glyoxylate. It is usually associated with the glyoxylate cycle
      in glyoxysomes, although the non-glyoxysomal form has been reported and its
      relation to interconversion of organic acids outside the glyoxylate cycle
      suggested. We investigated the expression of two isocitrate lyase genes and
      activities of the glyoxysomal (ICL1) and cytosolic (ICL2) forms of isocitrate
      lyase in amaranth (Amaranthus caudatus L.) seedlings. Both forms were separated
      and purified. The cytosolic form had a low optimum pH (6.5) and was activated by
      Mn(2+) ions, while Mg(2+) was ineffective, and had a lower affinity to d, l
      isocitrate (Km 63 MUM) as compared to the glyoxysomal form (optimum pH 7.5, K(m)
      45 MUM), which was activated by Mg(2+). The highest ICL1 activity was observed on
      the 3rd day of germination; then the activity and expression of the corresponding
      gene decreased, while the activity of ICL2 and gene expression increased to the
      7th day of germination and then remained at the same level. It is concluded that
      the function of ICL1 is related to the glyoxylate cycle while ICL2 functions
      independently from the glyoxylate cycle and interconverts organic acids in the
      cytosol.

PMID- 25955697
TI  - Salicylic acid and cysteine contribute to arbutin-induced alleviation of angular
      leaf spot disease development in cucumber.
AB  - Arbutin induced suppression of angular leaf spot disease in cucumber resulting
      from lower populations of Pseudomonas syringae pv lachrymans in the infected
      tissues. This study provides insight into mechanisms that may potentially account
      for this effect. In the absence of the pathogen, exogenous arbutin-induced
      expression of PR1, the marker of salicylic acid signaling, increased the content
      of salicylic acid and modulated the cysteine pool. This suggested that arbutin
      promoted cucumber plants to a "primed" state. When challenged with the pathogen,
      the arbutin-treated plants showed strongly reduced infection symptoms 7 days
      after inoculation. At this time point, they were characterized by higher contents
      of free and protein-bound cysteine due to higher cysteine biosynthetic capacity
      related to increased activities of serine acetyltransferase and cysteine synthase
      when compared with plants infected without arbutin treatment. Moreover, in the
      arbutin-treated and infected plants the contents of free salicylic acid and its
      conjugates were also increased, partly owing to its biosynthesis via the
      phenylpropanoid pathway. We suggest that arbutin-induced abrogation of angular
      leaf spot disease in cucumber could be mediated by salicylic acid and cysteine
      based signaling. 

PMID- 25955698
TI  - Doxorubicin impairs the insulin-like growth factor-1 system and causes insulin
      like growth factor-1 resistance in cardiomyocytes.
AB  - BACKGROUND: Insulin-like growth factor-1 (IGF-1) promotes the survival of
      cardiomyocytes by activating type 1 IGF receptor (IGF-1R). Within the myocardium,
      IGF-1 action is modulated by IGF binding protein-3 (IGFBP-3), which sequesters
      IGF-1 away from IGF-1R. Since cardiomyocyte apoptosis is implicated in
      anthracycline cardiotoxicity, we investigated the effects of the anthracycline,
      doxorubicin, on the IGF-1 system in H9c2 cardiomyocytes. METHODS AND RESULTS:
      Besides inducing apoptosis, concentrations of doxorubicin comparable to those
      observed in patients after bolus infusion (0.1-1 uM) caused a progressive
      decrease in IGF-1R and increase in IGFBP-3 expression. Exogenous IGF-1 was
      capable to rescue cardiomyocytes from apoptosis triggered by 0.1 and 0.5 uM, but
      not 1 uM doxorubicin. The loss of response to IGF-1 was paralleled by a
      significant reduction in IGF-1 availability and signaling, as assessed by free
      hormone levels in conditioned media and Akt phosphorylation in cell lysates,
      respectively. Doxorubicin also dose-dependently induced p53, which is known to
      repress the transcription of IGF1R and induce that of IGFBP3. Pre-treatment with
      the p53 inhibitor, pifithrin-alpha, prevented apoptosis and the changes in IGF-1R
      and IGFBP-3 elicited by doxorubicin. The decrease in IGF-1R and increase in IGFBP
      3, as well as apoptosis, were also antagonized by pre-treatment with the
      antioxidant agents, N-acetylcysteine, dexrazoxane, and carvedilol. CONCLUSIONS:
      Doxorubicin down-regulates IGF-1R and up-regulates IGFBP-3 via p53 and oxidative
      stress in H9c2 cells. This leads to resistance to IGF-1 that may contribute to
      doxorubicin-initiated apoptosis. Further studies are needed to confirm these
      findings in human cardiomyocytes and explore the possibility of manipulating the
      IGF-1 axis to protect against anthracycline cardiotoxicity.

PMID- 25955699
TI  - On the relation between Kaiser-Bessel blob and tube of response based modelling
      of the system matrix in iterative PET image reconstruction.
AB  - We investigate the question of how the blob approach is related to tube of
      response based modelling of the system matrix. In our model, the tube of response
      (TOR) is approximated as a cylinder with constant density (TOR-CD) and the cubic
      voxels are replaced by spheres. Here we investigate a modification of the TOR
      model that makes it effectively equivalent to the blob model, which models the
      intersection of lines of response (LORs) with radially variant basis functions
      ('blobs') replacing the cubic voxels. Implications of the achieved equivalence
      regarding the necessity of final resampling in blob-based reconstructions are
      considered. We extended TOR-CD to a variable density tube model (TOR-VD) that
      yields a weighting function (defining all system matrix elements) which is
      essentially identical to that of the blob model. The variable density of TOR-VD
      was modelled by a Gaussian and a Kaiser-Bessel function, respectively. The free
      parameters of both model functions were determined by fitting the corresponding
      weighting function to the weighting function of the blob model. TOR-CD and the
      best-fitting TOR-VD were compared to the blob model with a final resampling step
      (BLOB-RS) and without resampling (BLOB-NRS) in phantom studies. For three
      different contrast ratios and two different voxel sizes, resolution noise curves
      were generated. TOR-VD and BLOB-NRS lead to nearly identical images for all
      investigated contrast ratios and voxel sizes. Both models showed strong Gibbs
      artefacts at 4 mm voxel size, while at 2 mm voxel size there were no Gibbs
      artefacts visible. The spatial resolution was similar to the resolution with TOR
      CD in all cases. The resampling step removed most of the Gibbs artefacts and
      reduced the noise level but also degraded the spatial resolution substantially.
      We conclude that the blob model can be considered just as a special case of a TOR
      based reconstruction. The latter approach provides a more natural description of
      the detection process and allows for modifications that are not readily
      representable within the blob framework. 

PMID- 25955700
TI  - TBI at the Centers for Disease Control and Prevention.

PMID- 25955701
TI  - The Public Health Approach to TBI.

PMID- 25955702
TI  - Comparability of national estimates for traumatic brain injury-related medical
      encounters.
AB  - OBJECTIVE: To describe similarities and differences in the number of civilian
      traumatic brain injury (TBI)-related hospitalizations and emergency department
      visits between national databases that capture US hospital data. PARTICIPANTS:
      TBI-related hospitalizations included in the National Hospital Discharge Survey
      (NHDS) and Healthcare Cost and Utilization Project Nationwide Inpatient Sample
      (HCUP-NIS) and emergency department visits in the National Hospital Ambulatory
      Medical Care Survey (NHAMCS) and HCUP Nationwide Emergency Department Sample
      (HCUP-NEDS) for 2006-2010. DESIGN: Cross-sectional design. MAIN MEASURES:
      Nationwide counts of TBI-related medical encounters. RESULTS: Overall, the
      frequency of TBI is comparable when comparing NHDS with HCUP-NIS and NHAMCS with
      HCUP-NEDS. However, annual counts in both NHDS and NHAMCS are consistently
      unstable when examined in smaller subgroups, such as by age group and injury
      mechanism. Injury mechanism is consistently missing from many more records in
      NHDS compared with HCUP-NIS. CONCLUSION: Given the large sample size of HCUP-NIS
      and HCUP-NEDS, these data can offer a valuable resource for examining TBI-related
      hospitalization and emergency department visits, especially by subgroup. These
      data hold promise for future examinations of annual TBI counts, but ongoing
      comparisons with national probability samples will be necessary to ensure that
      HCUP continues to track with estimates from these data.

PMID- 25955703
TI  - Unemployment in the United States after traumatic brain injury for working-age
      individuals: prevalence and associated factors 2 years postinjury.
AB  - OBJECTIVE: To estimate the prevalence of unemployment and part-time employment in
      the United States for working-age individuals completing rehabilitation for a
      primary diagnosis of traumatic brain injury (TBI) between 2001 and 2010. DESIGN:
      Secondary data analysis. SETTING: Acute inpatient rehabilitation facilities.
      PARTICIPANTS: Patients aged 16 to 60 years at injury who completed inpatient
      rehabilitation for TBI between 2001 and 2010. MAIN OUTCOME MEASURES:
      Unemployment; Part-time employment. RESULTS: The prevalence of unemployment for
      persons in the selected cohort was 60.4% at 2-year postinjury. Prevalence of
      unemployment at 2-year postinjury was significantly associated with the majority
      of categories of age group, race, gender, marital status, primary inpatient
      rehabilitation payment source, education, preinjury vocational status, length of
      stay, and Disability Rating Scale. The direction of association for the majority
      of these variables complement previous research in this area, with only Hispanic
      ethnicity and the FIM Cognitive subscale demonstrating disparate findings. For
      those employed at 2-year postinjury, the prevalence of part-time employment was
      35.0%. The model of prevalence for part-time employment at 2-year postinjury was
      less robust, with significant relationships with some categorical components of
      age group, gender, marital status, primary payment source, preinjury vocational
      status, and Disability Rating Scale. CONCLUSIONS: The prevalence of unemployment
      for patients completing inpatient rehabilitation for TBI was substantial (60.4%).
      The majority of factors found to associate with 2 years' unemployment were
      complementary of previously published research; however, these were often smaller
      in magnitude than previous reports. The prevalence of part-time employment was
      also an issue for this cohort and included 35.0% of all employed individuals. In
      regard to the determination of factors associated with part-time employment,
      additional analyses that include more fine-grained factors associated with
      employment, including physical and psychosocial functioning, are recommended.

PMID- 25955704
TI  - Motorcycle crash-related emergency department visits and hospitalizations for
      traumatic brain injury in North Carolina.
AB  - OBJECTIVE: To examine statewide emergency department (ED) visit data for
      motorcycle crash morbidity and healthcare utilization due to traumatic brain
      injuries (TBIs) and non-TBIs. SETTING: North Carolina ED data (2010-2012) and
      hospital discharge data (2009-2011). POPULATION: Statewide ED visits and
      hospitalizations due to injuries from traffic-related motorcycle crashes
      stratified by TBI status. DESIGN: Descriptive study. MAIN MEASURES: Descriptive
      statistics include age, sex, mode of transport, disposition, expected source of
      payment, hospital length of stay, and hospital charges. RESULTS: Over the study
      period, there were 18 780 ED visits and 3737 hospitalizations due to motorcycle
      crashes. Twelve percent of ED visits for motorcycle crashes and 26% of
      hospitalizations for motorcycle crashes had a diagnosis of TBI. Motorcycle crash
      related hospitalizations with a TBI diagnosis had median hospital charges that
      were nearly $9000 greater than hospitalizations without a TBI diagnosis.
      CONCLUSIONS: Emergency department visits and hospitalizations due to motorcycle
      crashes with a TBI diagnosis consumed more healthcare resources than motorcycle
      crash-related ED visits and hospitalizations without a TBI diagnosis. Increased
      awareness of motorcyclists by other road users and increased use of motorcycle
      helmets are 2 strategies to mitigate the incidence and severity of motorcycle
      crash injuries, including TBIs.

PMID- 25955705
TI  - Trends in Sports- and Recreation-Related Traumatic Brain Injuries Treated in US
      Emergency Departments: The National Electronic Injury Surveillance System-All
      Injury Program (NEISS-AIP) 2001-2012.
AB  - IMPORTANCE: Sports- and recreation-related traumatic brain injuries (SRR-TBIs)
      are a growing public health problem affecting persons of all ages in the United
      States. OBJECTIVE: To describe the trends of SRR-TBIs treated in US emergency
      departments (EDs) from 2001 to 2012 and to identify which sports and recreational
      activities and demographic groups are at higher risk for these injuries. DESIGN:
      Data on initial ED visits for an SRR-TBI from the National Electronic Injury
      Surveillance System-All Injury Program (NEISS-AIP) for 2001-2012 were analyzed.
      SETTING: NEISS-AIP data are drawn from a nationally representative sample of
      hospital-based EDs. PARTICIPANTS: Cases of TBI were identified from approximately
      500,000 annual initial visits for all causes and types of injuries treated in EDs
      captured by NEISS-AIP. MAIN OUTCOME MEASURE(S): Numbers and rates by age group,
      sex, and year were estimated. Aggregated numbers and percentages by discharge
      disposition were produced. RESULTS: Approximately 3.42 million ED visits for an
      SRR-TBI occurred during 2001-2012. During this period, the rates of SRR-TBIs
      treated in US EDs significantly increased in both males and females regardless of
      age (all Ps < .001). For males, significant increases ranged from a low of 45.8%
      (ages 5-9) to a high of 139.8% (ages 10-14), and for females, from 25.1% (ages 0
      4) to 211.5% (ages 15-19) (all Ps < .001). Every year males had about twice the
      rates of SRR-TBIs than females. Approximately 70% of all SRR-TBIs were reported
      among persons aged 0 to 19 years. The largest number of SRR-TBIs among males
      occurred during bicycling, football, and basketball. Among females, the largest
      number of SRR-TBIs occurred during bicycling, playground activities, and
      horseback riding. Approximately 89% of males and 91% of females with an SRR-TBI
      were treated and released from EDs. CONCLUSION AND RELEVANCE: The rates of ED
      treated SRR-TBIs increased during 2001-2012, affecting mainly persons aged 0 to
      19 years and males in all age groups. Increases began to appear in 2004 for
      females and 2006 for males. Activities associated with the largest number of TBIs
      varied by sex and age. Reasons for the reported increases in ED visits are
      unknown but may be associated with increased awareness of TBI through increased
      media exposure and from campaigns, such as the Centers for Disease Control and
      Prevention's Heads Up. Prevention efforts should be targeted by sports and
      recreational activity, age, and sex.

PMID- 25955706
TI  - Reach and knowledge change among coaches and other participants of the online
      course: "concussion in sports: what you need to know".
AB  - OBJECTIVES: To describe the reach of the Heads Up "Concussion in Sports: What You
      Need to Know," online course and to assess knowledge change. SETTING: Online.
      PARTICIPANTS: Individuals who have taken the free online course since its
      inception in May 2010 to July 2013. DESIGN: Descriptive, uncontrolled, before and
      after study design. MAIN MEASURES: Reach is measured by the number of unique
      participants and the number of times the course was completed by state and sport
      coached and the rate of participation per 100,000 population by state. Knowledge
      change is measured by the distribution and mean of pre- and posttest scores by
      sex, primary role (e.g., coach, student, and parent), and sport coached. RESULTS:
      Between May 2010 and July 2013, the online concussion course was completed
      819,223 times, reaching 666,026 unique participants, including residents from all
      US states and the District of Columbia. The distribution of overall scores
      improved from pre- to posttests, with 21% answering all questions correctly on
      the pretest and 60% answering all questions correctly on the posttest.
      CONCLUSION: Online training can be effective in reaching large audiences and
      improving knowledge about emerging health and safety issues such as concussion
      awareness.

PMID- 25955708
TI  - Catalytic Transformation of Aldehydes with Nickel Complexes through eta(2)
      Coordination and Oxidative Cyclization.
AB  - Chemists no longer doubt the importance of a methodology that could activate and
      utilize aldehydes in organic syntheses since many products prepared from them
      support our daily life. Tremendous effort has been devoted to the development of
      these methods using main-group elements and transition metals. Thus, many organic
      chemists have used an activator-(aldehyde oxygen) interaction, namely, eta(1)
      coordination, whereby a Lewis or Bronsted acid activates an aldehyde. In the
      field of coordination chemistry, eta(2) coordination of aldehydes to transition
      metals by coordination of a carbon-oxygen double bond has been well-studied; this
      activation mode, however, is rarely found in transition-metal catalysis. In view
      of the distinctive reactivity of an eta(2)-aldehyde complex, unprecedented
      reactions via this intermediate are a distinct possibility. In this Account, we
      summarize our recent results dealing with nickel(0)-catalyzed transformations of
      aldehydes via eta(2)-aldehyde nickel and oxanickelacycle intermediates. The
      combination of electron-rich nickel(0) and strong electron-donating N
      heterocyclic carbene (NHC) ligands adequately form eta(2)-aldehyde complexes in
      which the aldehyde is highly activated by back-bonding. With Ni(0)/NHC catalysts,
      processes involving intramolecular hydroacylation of alkenes and homo/cross
      dimerization of aldehydes (the Tishchenko reaction) have been developed, and both
      proceed via the simultaneous eta(2) coordination of aldehydes and other pi
      components (alkenes or aldehydes). The results of the mechanistic studies are
      consistent with a reaction pathway that proceeds via an oxanickelacycle
      intermediate generated by the oxidative cyclization with a nickel(0) complex. In
      addition, we have used the eta(2)-aldehyde nickel complex as an effective
      activator for an organosilane in order to generate a silicate reactant. These
      reactions show 100% atom efficiency, generate no wastes, and are conducted under
      mild conditions. 

PMID- 25955707
TI  - Association of activated vitamin D use with myocardial fibrosis and capillary
      supply: results of an autopsy study.

PMID- 25955709
TI  - Highly valence-diversified binuclear uranium complexes of a schiff-base
      polypyrrolic macrocycle: prediction of unusual structures, electronic properties,
      and formation reactions.
AB  - On the basis of relativistic density functional theory calculations, homo- and
      heterovalent binuclear uranium complexes of a polypyrrolic macrocycle in a U-O-U
      bridging fashion have been investigated. These complexes show a variety of
      oxidation states for uranium ranging from III to VI, which have been confirmed by
      the calculated electron-spin density on each metal center. An equatorially 5-fold
      uranyl coordination mode is suitable for hexavalent uranium complexes, while
      silylation of the uranyl oxo is favored by pentavalent uranium. Uranyl oxo
      ligands are not required anymore for the coordination environment of tetra- and
      trivalent uranium because of their replacement by strong donors such as
      tetrahydrofuran and iodine. Optimization of binuclear U(VI)-U(III) complexes with
      various coordinating modes of U(III), donor numbers, and donor types reveals that
      0.5-1.0 electron has been transferred from U(III) to U(VI). Consequently, U(V)
      U(IV) complexes are more favorable. Electronic structures and formation reactions
      of several representative uranium complexes were calculated. For example, a 5f
      based sigma(U-U) bonding orbital is found in the diuranium(IV) complex,
      rationalizing the fact that it shows the shortest U-U distance (3.82 A) among the
      studied binuclear complexes. 

PMID- 25955710
TI  - Acceleration of conventional data acquisition in dynamic contrast enhancement:
      comparing keyhole approaches with compressive sensing.
AB  - Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) has become a
      valuable clinical tool for cancer diagnosis and prognosis. DCE MRI provides
      pharmacokinetic parameters dependent on the extravasation of small molecular
      contrast agents, and thus high temporal resolution and/or spatial resolution is
      required for accurate estimation of parameters. In this article we investigate
      the efficacy of 2 undersampling approaches to speed up DCE MRI: a conventional
      keyhole approach and compressed sensing-based imaging. Data reconstructed from
      variants of these methods has been compared with the full k-space reconstruction
      with respect to data quality and pharmacokinetic parameters Ktrans and ve.
      Overall, compressive sensing provides better data quality and reproducible
      parametric maps than key-hole methods with higher acceleration factors. In
      particular, an undersampling mask based on a priori precontrast data showed high
      fidelity of reconstructed data and parametric maps up to 5* acceleration. 

PMID- 25955711
TI  - A bidirectional model of postural sway using force plate data.
AB  - This work was designed to expand on our previous anterior-posterior postural
      control model to include medial-lateral sway of unperturbed posture during quiet
      standing. The bidirectional model simulates two decoupled inverted pendulums,
      each restricted to sway in either the anterior-posterior (AP) direction (ankle
      strategy) or medial-lateral (ML) direction (hip strategy), and each controlled by
      a Proportional-Integral-Derivative (PID) controller. Postural data was collected
      from 31 healthy participants under different sensory test conditions: eyes
      closed, eyes open, and eyes open with real-time visual feedback. Simulation
      iterations of the bidirectional model were run for each sensory test condition to
      adjust the PID controller parameters until modeled sway metrics did not differ
      significantly from experimental metrics at p <= 0.01. Simulations did not show
      significant changes in the AP sway controller parameters among the 3 sensory test
      conditions. The model did show significant changes in ML sway controller
      parameters, namely stiffness and time delay. Significant differences were also
      seen in the experimental sway metrics under the three different sensory test
      conditions. The multi-sensory evaluation and bidirectional sway model offer
      unique insight for further exploration of postural pathology, control mechanisms
      and planar coupling that includes both ankle and hip strategies. 

PMID- 25955713
TI  - Unconventional gradient coil designs in magnetic resonance imaging.
AB  - In magnetic resonance imaging (MRI), the gradient coils are used to encode the
      spatial positions of protons by varying the magnetic field linearly across the
      imaging subject. With the latest development of MRI technique and new clinical
      and research applications, the gradient coil system requires increasingly
      innovative designs. In this paper, four unconventional gradient coil designs are
      reviewed: (1) local gradient coils; (2) new coil configurations with reduced
      peripheral nerve stimulation (PNS); (3) dedicated structures designed for hybrid
      systems (combining MRI with other medical devices); and (4) the full 3D coil
      designs. For the first type, the development of local gradient coils (mainly head
      coils) is discussed chronologically and divided into three stages: the "golden"
      stage in the 1990s, the "wane" stage in the 2000s, and the "revival" stage in the
      2010s. For the second type, various designs for the reduction of PNS problems
      have been described, including local and whole-body gradient coil systems. For
      the third design, a dedicated gradient coil design for multi-modality combination
      is illustrated with an MRI-LINAC system. Finally, gradient systems with non
      layered coil structure are described in the fourth design type. We hope that this
      review on unconventional gradient coil designs will be useful for the new
      development of MRI technology and emerging medical applications. 

PMID- 25955712
TI  - Review of temperature dependence of thermal properties, dielectric properties,
      and perfusion of biological tissues at hyperthermic and ablation temperatures.
AB  - The application of supraphysiological temperatures (>40 degrees C) to biological
      tissues causes changes at the molecular, cellular, and structural level, with
      corresponding changes in tissue function and in thermal, mechanical and
      dielectric tissue properties. This is particularly relevant for image-guided
      thermal treatments (e.g. hyperthermia and thermal ablation) delivering heat via
      focused ultrasound (FUS), radiofrequency (RF), microwave (MW), or laser energy;
      temperature induced changes in tissue properties are of relevance in relation to
      predicting tissue temperature profile, monitoring during treatment, and
      evaluation of treatment results. This paper presents a literature survey of
      temperature dependence of electrical (electrical conductivity, resistivity,
      permittivity) and thermal tissue properties (thermal conductivity, specific heat,
      diffusivity). Data of soft tissues (liver, prostate, muscle, kidney, uterus,
      collagen, myocardium and spleen) for temperatures between 5 to 90 degrees C, and
      dielectric properties in the frequency range between 460 kHz and 3 GHz are
      reported. Furthermore, perfusion changes in tumors including carcinomas,
      sarcomas, rhabdomyosarcoma, adenocarcinoma and ependymoblastoma in response to
      hyperthmic temperatures up to 46 degrees C are presented. Where appropriate,
      mathematical models to describe temperature dependence of properties are
      presented. The presented data is valuable for mathematical models that predict
      tissue temperature during thermal therapies (e.g. hyperthermia or thermal
      ablation), as well as for applications related to prediction and monitoring of
      temperature induced tissue changes. 

PMID- 25955714
TI  - MicroRNA-29a inhibits cell migration and invasion by targeting Roundabout 1 in
      breast cancer cells.
AB  - Epithelial ovarian cancer (EOC) remains a major gynecological problem, with a
      poor 5-year-survival rate due to distant metastases. The identification of
      microRNAs (miRNAs) may provide a novel avenue for diagnostic and treatment
      regimens for EOC. Several miRNAs have been reported to be involved in the
      progression of EOC, among which miRNA (miR)-137 has been observed to be
      downregulated in the ovarian tissues of patients with EOC. However, the functions
      of miR-137 in EOC cell apoptosis, migration and invasion remain to be elucidated.
      In the present study, the expression of miR-137 was measured in clinical ovarian
      cancer specimens and cell lines using reverse transcription-quantitative
      polymerase chain reaction. The role of miR-137 in the growth and survival of the
      SKOV3 human ovarian cancer cell line was determined using several in vitro
      approaches and in nude mouse models. The results demonstrated that the expression
      of miR-137 was downregulated in the ovarian cancer specimens and cell lines. It
      was also observed that enforced expression of miR-137 in the EOC cell lines
      decreased cell proliferation, clonogenicity, migration and invasion, and induced
      G1 arrest and cell apoptosis in vitro. Notably, the enforced expression of miR
      137 suppressed tumor growth in the nude mice models. These findings suggested
      that miR-137 may act as a tumor suppressor and be used as a potential therapeutic
      agent for the treatment of EOC.

PMID- 25955716
TI  - Correction: Determining disease intervention strategies using spatially resolved
      simulations.

PMID- 25955715
TI  - A1M Ameliorates Preeclampsia-Like Symptoms in Placenta and Kidney Induced by Cell
      Free Fetal Hemoglobin in Rabbit.
AB  - Preeclampsia is one of the most serious pregnancy-related diseases and clinically
      manifests as hypertension and proteinuria after 20 gestational weeks. The
      worldwide prevalence is 3-8% of pregnancies, making it the most common cause of
      maternal and fetal morbidity and mortality. Preeclampsia lacks an effective
      therapy, and the only "cure" is delivery. We have previously shown that increased
      synthesis and accumulation of cell-free fetal hemoglobin (HbF) in the placenta is
      important in the pathophysiology of preeclampsia. Extracellular hemoglobin (Hb)
      and its metabolites induce oxidative stress, which may lead to acute renal
      failure and vascular dysfunction seen in preeclampsia. The human endogenous
      protein, alpha1-microglobulin (A1M), removes cell-free heme-groups and induces
      natural tissue repair mechanisms. Exogenously administered A1M has been shown to
      alleviate the effects of Hb-induced oxidative stress in rat kidneys. Here we
      attempted to establish an animal model mimicking the human symptoms at stage two
      of preeclampsia by administering species-specific cell-free HbF starting mid
      gestation until term, and evaluated the therapeutic effect of A1M on the induced
      symptoms. Female pregnant rabbits received HbF infusions i.v. with or without A1M
      every second day from gestational day 20. The HbF-infused animals developed
      proteinuria and a significantly increased glomerular sieving coefficient in
      kidney that was ameliorated by co-administration of A1M. Transmission electron
      microscopy analysis of kidney and placenta showed both intracellular and
      extracellular tissue damages after HbF-treatment, while A1M co-administration
      resulted in a significant reduction of the structural and cellular changes.
      Neither of the HbF-treated animals displayed any changes in blood pressure during
      pregnancy. In conclusion, infusion of cell-free HbF in the pregnant rabbits
      induced tissue damage and organ failure similar to those seen in preeclampsia,
      and was restored by co-administration of A1M. This study provides preclinical
      evidence supporting further examination of A1M as a potential new therapy for
      preeclampsia. 

PMID- 25955718
TI  - Expression and localization of interleukin 1 beta and interleukin 1 receptor
      (type I) in the bovine endometrium and embryo.
AB  - The interleukin-1 (IL1) system likely mediates mammalian embryo-maternal
      communication. In cattle, we have reported that the uterine fluid of heifers
      carrying early embryos shows downregulated IL1 beta (IL1B), which could lead to
      reduced NFkB expression and dampening of maternal innate immune responses. In
      this work, we assessed the expression of IL 1 beta (IL1B) and its receptor,
      interleukin 1 receptor type I (IL1R1) in the bovine endometrium and embryos by RT
      PCR, immunohistochemistry and Western blot at the time of blastocyst development.
      Day 8 endometrium, both collected from animals after transfer of day 5 embryos
      (ET) and sham transferred (ST), showed IL1B and IL1R1 mRNA transcription and
      protein co-localization. Similarly, day 8 blastocyst, from ET animals and
      entirely produced in vitro, showed IL1R1 mRNA transcription and IL1B and IL1R1
      protein co-localization. IL1B mRNA was detected in the analyzed blastocysts, but
      at very low levels that precluded its quantification. IL1B and IL1R1
      immunostaining was observed in luminal epithelial cells, glandular epithelium and
      stromal cells. The presence of embryos increased endometrial IL1B protein
      locally, while no differences regarding IL1R1 protein and IL1B and IL1R1 mRNA
      were detected. These results suggest that the early preimplantation bovine embryo
      in the maternal tract might interact with the maternal immune system through the
      IL1 system. Such a mechanism may allow the embryo to elicit local endometrial
      responses at early stages, which are required for the development of a receptive
      endometrium. 

PMID- 25955717
TI  - Human Cytomegalovirus miR-UL112-3p Targets TLR2 and Modulates the
      TLR2/IRAK1/NFkappaB Signaling Pathway.
AB  - Human Cytomegalovirus (HCMV) encodes multiple microRNAs (miRNAs) whose functions
      are just beginning to be uncovered. Using in silico approaches, we identified the
      Toll-Like Receptor (TLR) innate immunity pathway as a possible target of HCMV
      miRNAs. Luciferase reporter assay screens further identified TLR2 as a target of
      HCMV miR-UL112-3p. TLR2 plays a major role in innate immune response by detecting
      both bacterial and viral ligands, including HCMV envelope proteins gB and gH.
      TLR2 activates a variety of signal transduction routes including the NFkappaB
      pathway. Furthermore, TLR2 plays an important role in controlling CMV infection
      both in humans and in mice. Immunoblot analysis of cells transfected with a miR
      UL112-3p mimic revealed that endogenous TLR2 is down-regulated by miR-UL112-3p
      with similar efficiency as a TLR2-targeting siRNA (siTLR2). We next found that
      TLR2 protein level decreases at late times during HCMV infection and correlates
      with miR-UL112-3p accumulation in fibroblasts and monocytic THP1 cells.
      Confirming direct miR-UL112-3p targeting, down-regulation of endogenous TLR2 was
      not observed in cells infected with HCMV mutants deficient in miR-UL112-3p
      expression, but transfection of miR-UL112-3p in these cells restored TLR2 down
      regulation. Using a NFkappaB reporter cell line, we found that miR-UL112-3p
      transfection significantly inhibited NFkappaB-dependent luciferase activity with
      similar efficiency as siTLR2. Consistent with this observation, miR-UL112-3p
      transfection significantly reduced the expression of multiple cytokines (IL
      1beta, IL-6 and IL-8) upon stimulation with a TLR2 agonist. Finally, miR-UL112-3p
      transfection significantly inhibited the TLR2-induced post-translational
      activation of IRAK1, a kinase located in the upstream section of the
      TLR2/NFkappaB signaling axis. To our knowledge, this is the first identified
      mechanism of TLR2 modulation by HCMV and is the first report of functional
      targeting of TLR2 by a viral miRNA. These results provide a novel mechanism
      through which a HCMV miRNA regulates the innate immune response by down
      regulating TLR-2 expression. 

PMID- 25955719
TI  - Origin of Emotion Effects on ERP Correlates of Emotional Word Processing: The
      Emotion Duality Approach.
AB  - We distinguish two evaluative systems which evoke automatic and reflective
      emotions. Automatic emotions are direct reactions to stimuli whereas reflective
      emotions are always based on verbalized (and often abstract) criteria of
      evaluation. We conducted an electroencephalography (EEG) study in which 25 women
      were required to read and respond to emotional words which engaged either the
      automatic or reflective system. Stimulus words were emotional (positive or
      negative) and neutral. We found an effect of valence on an early response with
      dipolar fronto-occipital topography; positive words evoked a higher amplitude
      response than negative words. We also found that topographically specific
      differences in the amplitude of the late positive complex were related to the
      system involved in processing. Emotional stimuli engaging the automatic system
      were associated with significantly higher amplitudes in the left-parietal region;
      the response to neutral words was similar regardless of the system engaged. A
      different pattern of effects was observed in the central region, neutral stimuli
      engaging the reflective system evoked a higher amplitudes response whereas there
      was no system effect for emotional stimuli. These differences could not be
      reduced to effects of differences between the arousing properties and
      concreteness of the words used as stimuli. 

PMID- 25955721
TI  - Implementation of interprofessional learning activities in a professional
      practicum: The emerging role of technology.
AB  - To prepare future healthcare professionals to collaborate effectively, many
      universities have developed interprofessional education programs (IPE). Till
      date, these programs have been mostly courses or clinical simulation experiences.
      Few attempts have been made to pursue IPE in healthcare clinical settings. This
      article presents the results of a pilot project in which interprofessional
      learning activities (ILAs) were implemented during students' professional
      practicum and discusses the actual and potential use of informatics in the ILA
      implementation. We conducted a pilot study in four healthcare settings. Our
      analysis is based on focus group interviews with trainees, clinical supervisors,
      ILA coordinators, and education managers. Overall, ILAs led to better
      clarification of roles and understanding of each professional's specific
      expertise. Informatics was helpful for developing a common language about IPE
      between trainees and healthcare professionals; opportunities for future
      application of informatics were noted. Our results support the relevance of ILAs
      and the value of promoting professional exchanges between students of different
      professions, both in academia and in the clinical setting. Informatics appears to
      offer opportunities for networking among students from different professions and
      for team members' professional development. The use of technology facilitated
      communication among the participants. 

PMID- 25955722
TI  - Beneficial effects of an intradialytic cycling training program in patients with
      end-stage kidney disease.
AB  - In chronic kidney disease (CKD), oxidative stress (OS) plays a central role in
      the development of cardiovascular diseases. This pilot program aimed to determine
      whether an intradialytic aerobic cycling training protocol, by increasing
      physical fitness, could reduce OS and improve other CKD-related disorders such as
      altered body composition and lipid profile. Eighteen hemodialysis patients were
      randomly assigned to either an intradialytic training (cycling: 30 min, 55%-60%
      peak power, 3 days/week) group (EX; n = 8) or a control group (CON; n = 10) for 3
      months. Body composition (from dual-energy X-ray absorptiometry), physical
      fitness (peak oxygen uptake and the 6-minute walk test (6MWT)), lipid profile
      (triglycerides (TG), total cholesterol, high-density lipoprotein, and low-density
      lipoprotein (LDL)), and pro/antioxidant status (15-F2alpha-isoprostanes (F2-IsoP)
      and oxidized LDL in plasma; superoxide dismutase, glutathione peroxidase, and
      reduced/oxidized glutathione in erythrocytes) were determined at baseline and 3
      months later. The intradialytic training protocol did not modify body composition
      but had significant effects on physical fitness, lipid profile, and
      pro/antioxidant status. Indeed, at 3 months: (i) performance on the 6MWT was
      increased in EX (+23.4%, p < 0.001) but did not change in CON, (ii) plasma TG
      were reduced in EX (-23%, p < 0.03) but were not modified in CON, and (iii)
      plasma F2-IsoP concentrations were lower in EX than in CON (-35.7%, p = 0.02). In
      conclusion, our results show that 30 min of intradialytic training, 3 times per
      week for 3 months, are enough to exert beneficial effects on the most sensitive
      and reliable marker of lipid peroxidation (IsoP) while improving CKD-associated
      disorders (lipid profile and physical fitness). Intradialytic aerobic cycling
      training represents a useful and easy strategy to reduce CKD-associated
      disorders. These results need to be confirmed with a larger randomized study. 

PMID- 25955727
TI  - Proton-Coupled Electron Transfer Constitutes the Photoactivation Mechanism of the
      Plant Photoreceptor UVR8.
AB  - UVR8 is a novel UV-B photoreceptor that regulates a range of plant responses and
      is already used as a versatile optogenetic tool. Instead of an exogenous
      chromophore, UVR8 uniquely employs tryptophan side chains to accomplish UV-B
      photoreception. UV-B absorption by homodimeric UVR8 induces monomerization and
      hence signaling, but the underlying photodynamic mechanisms are not known. Here,
      by using a combination of time-resolved fluorescence and absorption spectroscopy
      from femto- to microseconds, we provide the first experimental evidence for the
      UVR8 molecular signaling mechanism. The results indicate that tryptophan residues
      at the dimer interface engage in photoinduced proton coupled electron transfer
      reactions that induce monomerization. 

PMID- 25955720
TI  - Muscle Releases Alpha-Sarcoglycan Positive Extracellular Vesicles Carrying miRNAs
      in the Bloodstream.
AB  - In the past few years, skeletal muscle has emerged as an important secretory
      organ producing soluble factors, called myokines, that exert either autocrine,
      paracrine or endocrine effects. Moreover, recent studies have shown that muscle
      releases microRNAs into the bloodstream in response to physical exercise. These
      microRNAs affect target cells, such as hormones and cytokines. The mechanisms
      underlying microRNA secretion are poorly characterized at present. Here, we
      investigated whether muscle tissue releases extracellular vesicles (EVs), which
      carry microRNAs in the bloodstream under physiological conditions such as
      physical exercise. Using density gradient separation of plasma from sedentary and
      physically fit young men we found EVs positive for TSG101 and alpha-sarcoglycan
      (SGCA), and enriched for miR-206. Cytometric analysis showed that the SGCA+ EVs
      account for 1-5% of the total and that 60-65% of these EVs were also positive for
      the exosomal marker CD81. Furthermore, the SGCA-immuno captured sub-population of
      EVs exhibited higher levels of the miR-206/miR16 ratio compared to total plasma
      EVs. Finally, a significant positive correlation was found between the aerobic
      fitness and muscle-specific miRNAs and EV miR-133b and -181a-5p were
      significantly up-regulated after acute exercise. Thus, our study proposes EVs as
      a novel means of muscle communication potentially involved in muscle remodeling
      and homeostasis. 

PMID- 25955729
TI  - Phylogenetic signal dissection identifies the root of starfishes.
AB  - Relationships within the class Asteroidea have remained controversial for almost
      100 years and, despite many attempts to resolve this problem using molecular
      data, no consensus has yet emerged. Using two nuclear genes and a taxon sampling
      covering the major asteroid clades we show that non-phylogenetic signal created
      by three factors--Long Branch Attraction, compositional heterogeneity and the use
      of poorly fitting models of evolution--have confounded accurate estimation of
      phylogenetic relationships. To overcome the effect of this non-phylogenetic
      signal we analyse the data using non-homogeneous models, site stripping and the
      creation of subpartitions aimed to reduce or amplify the systematic error, and
      calculate Bayes Factor support for a selection of previously suggested
      topological arrangements of asteroid orders. We show that most of the previous
      alternative hypotheses are not supported in the most reliable data partitions,
      including the previously suggested placement of either Forcipulatida or
      Paxillosida as sister group to the other major branches. The best-supported
      solution places Velatida as the sister group to other asteroids, and the
      implications of this finding for the morphological evolution of asteroids are
      presented.

PMID- 25955728
TI  - HSA21 Single-Minded 2 (Sim2) Binding Sites Co-Localize with Super-Enhancers and
      Pioneer Transcription Factors in Pluripotent Mouse ES Cells.
AB  - The HSA21 encoded Single-minded 2 (SIM2) transcription factor has key
      neurological functions and is a good candidate to be involved in the cognitive
      impairment of Down syndrome. We aimed to explore the functional capacity of SIM2
      by mapping its DNA binding sites in mouse embryonic stem cells. ChIP-sequencing
      revealed 1229 high-confidence SIM2-binding sites. Analysis of the SIM2 target
      genes confirmed the importance of SIM2 in developmental and neuronal processes
      and indicated that SIM2 may be a master transcription regulator. Indeed, SIM2 DNA
      binding sites share sequence specificity and overlapping domains of occupancy
      with master transcription factors such as SOX2, OCT4 (Pou5f1), NANOG or KLF4. The
      association between SIM2 and these pioneer factors is supported by co
      immunoprecipitation of SIM2 with SOX2, OCT4, NANOG or KLF4. Furthermore, the
      binding of SIM2 marks a particular sub-category of enhancers known as super
      enhancers. These regions are characterized by typical DNA modifications and
      Mediator co-occupancy (MED1 and MED12). Altogether, we provide evidence that SIM2
      binds a specific set of enhancer elements thus explaining how SIM2 can regulate
      its gene network in neuronal features. 

PMID- 25955730
TI  - Association between Polymorphisms in Vascular Endothelial Growth Factor Gene and
      Response to Chemotherapies in Colorectal Cancer: A Meta-Analysis.
AB  - BACKGROUND: Some studies have investigated the effects of polymorphisms in the
      vascular endothelial growth factor (VEGF) gene on responsiveness to chemotherapy
      for colorectal cancer (CRC) and have shown inconclusive results. METHODS:
      Eligible studies that assessed the associations between polymorphisms in the VEGF
      gene and response to chemotherapy in CRC were searched in the PubMed, Embase and
      Medline databases until November 2014. Odds ratios (OR) and 95% confidence
      intervals (CIs) were used to evaluate the associations, using Review Manager
      software, version 5.3. Stratified analysis was also conducted. RESULTS: In the
      overall analysis, a significant association with responsiveness to chemotherapy
      in CRC was identified in CC vs. CA of the VEGF -2578 C/A polymorphism (OR = 1.40,
      95% CI 1.00-1.97, P = 0.05) and in CC+CT vs. TT of the VEGF -460 C/T polymorphism
      (OR = 0.71, 95% CI 0.53-0.96, P = 0.02). In subgroup analysis, a significant
      association was found in excluding anti-angiogenic agent subgroup in three
      comparison models of the VEGF -2578 C/A polymorphism and another three genetic
      models of the VEGF -460 C/T C/A polymorphism. CONCLUSIONS: CC vs. CA of the VEGF 
      2578 C/A polymorphism and CC+CT vs. TT of the VEGF -460 C/T polymorphism might be
      predictive factors of responsiveness to chemotherapy in CRC. However, single
      nucleotide polymorphisms in the VEGF gene lacked sufficient predictive ability to
      determine whether patients with CRC should add anti-angiogenic agents to their
      chemotherapy regimens.

PMID- 25955732
TI  - AAFP challenges payment inequities in primary care, oncology initiatives.

PMID- 25955731
TI  - Dual inhibition of EGFR and MET induces synthetic lethality in triple-negative
      breast cancer cells through downregulation of ribosomal protein S6.
AB  - Triple-negative breast cancer (TNBC) exhibits innate resistance to the EGFR
      inhibition despite high level expression of EGFR. Recently, we found that the
      proliferation of basal-like (BL) subtype TNBC cells is synergistically inhibited
      by combination of EGFR and PI3K/AKT inhibitors. On the contrary, TNBC cells of
      mesenchymal stem-like (MSL) subtype are resistant to these combinations. To
      identify potential synthetic lethal interaction of compounds for treatment of MSL
      subtype TNBC cells, we performed MTT screening of MDA-MB-231 cells with a small
      library of receptor tyrosine kinase inhibitors (RTKIs) in the presence of
      gefitinib, an EGFR inhibitor. We identified MET inhibitors as potent RTKIs that
      caused synthetic lethality in combination with gefitinib in MDA-MB-231 cells. We
      demonstrated that combination of a MET inhibitor SU11274 with various EGFR
      inhibitors resulted in synergistic suppression of cell viability (in MTT assay)
      and cell survival (in colony formation assay) of MSL subtype TNBC cells. We
      further demonstrated that SU11274 alone induced G2 arrest and gefitinib/SU11274
      combination sustained the SU11274-induced G2 arrest in these cells. In addition,
      SU11274/gefitinib combination synergistically reduced the level of ribosomal
      protein S6 (RPS6) in MSL subtype TNBC cells. In addition, knockdown of RPS6
      itself, in both HS578T and MDA-MB-231, markedly reduced the proliferation of
      these cells. Taken together, our data suggest that dual targeting of EGFR and MET
      inhibits the proliferation of MSL subtype TNBC cells through downregulation of
      RPS6.

PMID- 25955733
TI  - The Continuing Evolution of AFP Online.

PMID- 25955734
TI  - The maternal health benefits of breastfeeding.

PMID- 25955735
TI  - FPIN's Clinical Inquiries. Treatments for sciatica.

PMID- 25955736
TI  - Diagnosis and management of generalized anxiety disorder and panic disorder in
      adults.
AB  - Generalized anxiety disorder (GAD) and panic disorder (PD) are among the most
      common mental disorders in the United States, and they can negatively impact a
      patient's quality of life and disrupt important activities of daily living.
      Evidence suggests that the rates of missed diagnoses and misdiagnosis of GAD and
      PD are high, with symptoms often ascribed to physical causes. Diagnosing GAD and
      PD requires a broad differential and caution to identify confounding variables
      and comorbid conditions. Screening and monitoring tools can be used to help make
      the diagnosis and monitor response to therapy. The GAD-7 and the Severity Measure
      for Panic Disorder are free diagnostic tools. Successful outcomes may require a
      combination of treatment modalities tailored to the individual patient. Treatment
      often includes medications such as selective serotonin reuptake inhibitors and/or
      psychotherapy, both of which are highly effective. Among psychotherapeutic
      treatments, cognitive behavior therapy has been studied widely and has an
      extensive evidence base. Benzodiazepines are effective in reducing anxiety
      symptoms, but their use is limited by risk of abuse and adverse effect profiles.
      Physical activity can reduce symptoms of GAD and PD. A number of complementary
      and alternative treatments are often used; however, evidence is limited for most.
      Several common botanicals and supplements can potentiate serotonin syndrome when
      used in combination with antidepressants. Medication should be continued for 12
      months before tapering to prevent relapse.

PMID- 25955737
TI  - Provision of Contraception: Key Recommendations from the CDC.
AB  - The Centers for Disease Control and Prevention has released comprehensive
      recommendations for provision of family planning services. Contraceptive services
      may be addressed in five steps, and counseling may be provided in a tiered
      approach, whereby the most effective options are presented before less effective
      options. Clinicians should discuss all contraceptive methods that can be used
      safely by the patient, regardless of whether a method is available on site and
      even if the patient is an adolescent or a nulliparous woman. Physical assessment
      is usually limited to blood pressure evaluation before starting hormonal
      contraceptives or pelvic examination before placing an intrauterine device.
      Monitoring the patient's weight also may be helpful. If it is reasonably certain
      that the patient is not pregnant, any contraceptive may be started immediately.
      When hormonal contraceptives are selected, one year's supply should be prescribed
      to reduce barriers to use. Condoms should be made readily available.
      Documentation of visits for contraception should include patient understanding of
      use, benefits, and risks, plus an individualized follow-up plan. Bleeding
      irregularities generally are not harmful and may resolve with continued use of
      the contraceptive method. All patients-including adolescents; those who identify
      as lesbian, gay, bisexual, or transgender; and patients with disabilities or
      limited English proficiency-should receive high-quality care in an accommodating,
      nonjudgmental environment. The Centers for Disease Control and Prevention
      supports advance provision of emergency contraceptives. Because no test reliably
      verifies cessation of fertility, it is prudent to consider contraceptive use
      until menopause, or at least until 50 to 55 years of age.

PMID- 25955738
TI  - Nutrition myths and healthy dietary advice in clinical practice.
AB  - Healthy dietary intake is important for the maintenance of general health and
      wellness, the prevention of chronic illness, the optimization of life expectancy,
      and the clinical management of virtually all disease states. Dietary myths (i.e.,
      concepts about nutrition that are poorly supported or contradicted by scientific
      evidence) may stand in the way of healthy dietary intake. Dietary myths exist
      about micronutrients, macronutrients, non-nutrients, and food energy.
      Representative myths of each type include that patients need to focus on
      consuming enough calcium to ensure bone health, dietary fat leads to obesity and
      is detrimental to vascular health, all fiber (whether naturally occurring or
      artificially added) is beneficial, and food calories translate to pounds of body
      weight through a linear relationship and simple arithmetic. A common theme for
      dietary myths is a reductionist view of diet that emphasizes selected food
      constituents as opposed to whole foods. Healthy dietary advice takes a more
      holistic view; consistent evidence supports recommendations to limit the
      consumption of ultraprocessed foods and to eat whole or minimally processed
      foods, generally in a form that is as close to what occurs in nature as possible.
      Family physicians can help dispel myths for patients and give sound nutritional
      advice by focusing on actual foods and broader dietary patterns.

PMID- 25955739
TI  - Caring for Muslim patients who fast during Ramadan.

PMID- 25955746
TI  - PSA Screening for Prostate Cancer.

PMID- 25955743
TI  - A geometric summertime rash.

PMID- 25955748
TI  - Help for anxiety and panic disorders.

PMID- 25955749
TI  - Birth control: what you should know.

PMID- 25955751
TI  - Highlights from the 1st ISCB Latin American Student Council Symposium 2014.
      Introduction.
AB  - This report summarizes the scientific content and activities of the first edition
      of the Latin American Symposium organized by the Student Council of the
      International Society for Computational Biology (ISCB), held in conjunction with
      the Third Latin American conference from the International Society for
      Computational Biology (ISCB-LA 2014) in Belo Horizonte, Brazil, on October 27,
      2014.

PMID- 25955750
TI  - Hearing Loss After Activation of Hearing Preservation Cochlear Implants Might Be
      Related to Afferent Cochlear Innervation Injury.
AB  - OBJECTIVE: Characterize hearing loss (HL) after hearing preservation cochlear
      implantation and determine the association between high charge electrical
      stimulation (ES) and late loss of acoustic hearing. METHODS: A retrospective
      cohort analysis of all hearing preservation implantees at our center (n = 42)
      assayed HL as a function of maximum charge. We analyzed serial audiometry from 85
      patients enrolled in the multicenter Hybrid S8 trial to detail the hearing loss
      greater than 1 month after implantation. Cochleotypic explant cultures were used
      to assess susceptibility to high levels of ES. RESULTS: Early HL after
      implantation tends to be mild and averages 12.2 dB. After activation of the
      Hybrid S8 device, 17 (20%) of 85 patients experienced acceleration of HL.
      Compared with the majority of patients who did not lose significant hearing after
      activation, these patients experienced more severe HL at 1 year. Five patients
      implanted at our center experienced acceleration of HL after high charge
      exposure. In patients implanted at our center, high charge was associated with
      late HL (Pearson 0.366, p = 0.016). In rat cochleotypic explants, high voltage ES
      damaged afferent nerve fibers, reflected by blebbing and a 50% reduction in the
      number of fibers innervating the organ of Corti. In contrast, hair cells
      displayed only minor differences in cell number and morphology. CONCLUSIONS:
      Based on clinical and in vitro data, we theorize that the combination of acoustic
      amplification and ES in the setting of intact hair cells and neural architecture
      may contribute, in part, to cochlear toxicity, perhaps by damaging the afferent
      innervation.

PMID- 25955752
TI  - Optimization of gap derivatives for measuring blood concentration of fabric using
      vibrational spectroscopy.
AB  - Derivatives are common preprocessing tools, typically implemented as Savitzky
      Golay (SG) smoothing derivatives. This work discusses the implementation and
      optimization of fourth-order gap derivatives (GDs) as an alternative to SG
      derivatives for processing infrared spectra before multivariate calibration. Gap
      derivatives approximate the analytical derivative by calculating finite
      differences of spectra without curve fitting. Gap derivatives offer an advantage
      of tunability for spectral data as the distance (gap) over which this finite
      difference is calculated can be varied. Gap selection is a compromise between
      signal attenuation, noise amplification, and spectral resolution. A method and
      discussion of the importance of fourth derivative gap selections are presented as
      well as a comparison to SG preprocessing and lower-order GDs in the context of
      multivariate calibration. In most cases, we found that optimized GDs led to
      calibration models performing comparably to or better than SG derivatives, and
      that optimized fourth-order GDs behaved similarly to matched filters. 

PMID- 25955753
TI  - Differential HIF-1alpha and HIF-2alpha Expression in Mammary Epithelial Cells
      during Fat Pad Invasion, Lactation, and Involution.
AB  - The development and functional cycle of the mammary gland involves a number of
      processes that are caricatured by breast cancer cells during invasion and
      metastasis. Expression of the hypoxia-inducible transcription factors HIF-1 and
      HIF-2 has been associated with metastatic, poor prognosis, and high-grade breast
      cancers. Since hypoxia affects normal epithelial differentiation, we hypothesise
      that HIFs are important for normal breast epithelial development and regeneration
      as well as cancer initiation and progression. Here, we investigated the
      expression of the oxygen-sensitive HIF-alpha subunits during mouse mammary gland
      development, lactation, and involution. In breast epithelial cells, HIF-1alpha
      was expressed during early development, prior to cell polarisation. In contrast,
      expression of HIF-2alpha occurred later and was restricted to a subpopulation of
      luminal epithelial cells in the lactating gland. Mammary gland involution is a
      developmental stage that involves extensive tissue remodelling with cell death
      but survival of tissue stem/progenitor cells. At this stage, HIF-2alpha, but
      little HIF-1alpha, was expressed in CK14-positive epithelial cells. The temporal
      but differential expression of the HIF-alpha subunits during the mammary gland
      life cycle indicates that their expression is controlled by additional factors to
      hypoxia. Further functional studies of the roles of these proteins in the mammary
      gland and breast cancer are warranted. 

PMID- 25955754
TI  - Perspective on the use of sulfated polysaccharides from marine organisms as a
      source of new antithrombotic drugs.
AB  - Thromboembolic diseases are increasing worldwide and always require anticoagulant
      therapy. We still need safer and more secure antithrombotic drugs than those
      presently available. Sulfated polysaccharides from marine organisms may
      constitute a new source for the development of such drugs. Investigation of these
      compounds usually attempts to reproduce the therapeutic effects of heparin.
      However, we may need to follow different routes, focusing particularly in the
      following aspects: (1) defining precisely the specific structures required for
      interaction of these sulfated polysaccharides with proteins of the coagulation
      system; (2) looking for alternative mechanisms of action, distinct from those of
      heparin; (3) identifying side effects (mostly pro-coagulant action and
      hypotension rather than bleeding) and preparing derivatives that retain the
      desired antithrombotic action but are devoid of side effects; (4) considering
      that sulfated polysaccharides with low anticoagulant action on in vitro assays
      may display potent effects on animal models of experimental thrombosis; and
      finally (5) investigating the antithrombotic effect of these sulfated
      polysaccharides after oral administration or preparing derivatives that may
      achieve this effect. If these aspects are successfully addressed, sulfated
      polysaccharides from marine organisms may conquer the frontier of antithrombotic
      therapy and open new avenues for treatment or prevention of thromboembolic
      diseases. 

PMID- 25955755
TI  - Natural Marine and Synthetic Xenobiotics Get on Nematode's Nerves: Neuro
      Stimulating and Neurotoxic Findings in Caenorhabditis elegans.
AB  - Marine algae release a plethora of organic halogenated compounds, many of them
      with unknown ecological impact if environmentally realistic concentrations are
      applied. One major compound is dibromoacetic acid (DBAA) which was tested for
      neurotoxicity in the invertebrate model organism Caenorhabditis elegans (C.
      elegans). This natural compound was compared with the widespread synthetic
      xenobiotic tetrabromobisphenol-A (TBBP-A) found in marine sediments and mussels.
      We found a neuro-stimulating effect for DBAA; this is contradictory to existing
      toxicological reports of mammals that applied comparatively high dosages. For
      TBBP-A, we found a hormetic concentration-effect relationship. As chemicals
      rarely occur isolated in the environment, a combination of both organobromines
      was also examined. Surprisingly, the presence of DBAA increased the toxicity of
      TBBP-A. Our results demonstrated that organohalogens have the potential to affect
      single organisms especially by altering the neurological processes, even with
      promoting effects on exposed organisms. 

PMID- 25955756
TI  - Tilapia Piscidin 4 (TP4) Stimulates Cell Proliferation and Wound Closure in MRSA
      Infected Wounds in Mice.
AB  - Antimicrobial peptides (AMPs) are endogenous antibiotics that directly affect
      microorganisms, and also have a variety of receptor-mediated functions. One such
      AMP, Tilapia piscidin 4 (TP4), was isolated from Nile tilapia (Oreochromis
      niloticus); TP4 has antibacterial effects and regulates the innate immune system.
      The aim of the present study was to characterize the role of TP4 in the
      regulation of wound closure in mice and proliferation of a keratinocyte cell line
      (HaCaT) and fibroblast cell line (Hs-68). In vitro, TP4 stimulated cell
      proliferation and activated collagen I, collagen III, and keratinocyte growth
      factor (KGF) gene expression in Hs-68 cells, which induces keratin production by
      HaCaT cells. This effect was detectable at TP4 concentrations of 6.25 ug/mL in
      both cell lines. In vivo, TP4 was found to be highly effective at combating
      peritonitis and wound infection caused by MRSA in mouse models, without inducing
      adverse behavioral effects or liver or kidney toxicity. Taken together, our
      results indicate that TP4 enhances the survival rate of mice infected with the
      bacterial pathogen MRSA through both antimicrobial and wound closure activities
      mediated by epidermal growth factor (EGF), transforming growth factor (TGF), and
      vascular endothelial growth factor (VEGF). The peptide is likely involved in
      antibacterial processes and regulation of tissue homeostasis in infected wounds
      in mice. Overall, these results suggest that TP4 may be suitable for development
      as a novel topical agent for wound dressing. 

PMID- 25955757
TI  - The effect of dissolved polyunsaturated aldehydes on microzooplankton growth
      rates in the Chesapeake Bay and Atlantic coastal waters.
AB  - Allelopathy is wide spread among marine phytoplankton, including diatoms, which
      can produce cytotoxic secondary metabolites such as polyunsaturated aldehydes
      (PUA). Most studies on diatom-produced PUA have been dedicated to their
      inhibitory effects on reproduction and development of marine invertebrates.
      However, little information exists on their impact on key herbivores in the
      ocean, microzooplankton. This study examined the effects of dissolved 2E,4E
      octadienal and 2E,4E-heptadienal on the growth rates of natural ciliate and
      dinoflagellate populations in the Chesapeake Bay and the coastal Atlantic waters.
      The overall effect of PUA on microzooplankton growth was negative, especially at
      the higher concentrations, but there were pronounced differences in response
      among common planktonic species. For example, the growth of Codonella sp.,
      Leegaardiella sol, Prorodon sp., and Gyrodinium spirale was impaired at 2 nM,
      whereas Strombidium conicum, Cyclotrichium gigas, and Gymnodinium sp. were not
      affected even at 20 nM. These results indicate that PUA can induce changes in
      microzooplankton dynamics and species composition. 

PMID- 25955759
TI  - The anticancer effect of Huaier (Review).
AB  - Trametes robiniophila Murr. (Huaier) is a sandy beige mushroom found on the
      trunks of trees and has been widely used in traditional Chinese medicine (TCM)
      for ~1,600 years. The anticancer effects of Huaier have attracted increasing
      worldwide interest in recent years. Accumulating evidence suggests that the
      anticancer mechanism of Huaier may be associated with various biological
      activities, such as inhibition of cell proliferation, anti-metastasis,
      interference with tumor angiogenesis and tumor-specific immunomodulatory effect.
      Animal and experimental studies suggest that Huaier is a promising anticancer
      agent. Further clinical research is warranted to illustrate the untapped
      chemopreventive and therapeutic potential of Huaier either alone or in
      conjunction with existing therapies.

PMID- 25955758
TI  - Screening biomarkers of bladder cancer using combined miRNA and mRNA microarray
      analysis.
AB  - Biomarkers, such as microRNAs (miRNAs) may be useful for the diagnosis of bladder
      cancer. In order to understand the molecular mechanisms underlying bladder
      cancer, differentially expressed miRNAs (DE-miRNAs) and their target genes in
      bladder cancer were analyzed. In the present study, miRNA and mRNA expression
      profiles (GSE40355) were obtained from the Gene Expression Omnibus. These
      consisted of healthy bladder samples (n=8) and urothelial carcinoma samples (low
      grade, n=8 and high-grade, n=8). DE-miRNAs and differentially expressed genes
      (DEGs) were identified using the limma package and the Benjamin and Hochberg
      method from the multtest package in R. Target genes of DE-miRNAs were screened.
      Associations between DEGs were investigated using STRING, and an interaction
      network was constructed using Cytoscape. Functional and pathway enrichment
      analyses were performed for DEGs from the interaction network. 87 DE-miRNAs and
      2058 DEGs were screened from low-grade bladder cancer samples, and 40 DE-miRNAs
      and 2477 DEGs were screened from high-grade bladder cancer samples. DE-target
      genes were significantly associated with the regulation of cell apoptosis.
      Bladder cancer, non-small cell lung cancer and pancreatic cancer biological
      pathways were found to be enriched. The results of the present study demonstrated
      that E2F transcription factor 1, which is targeted by miR-106b, and cyclin
      dependent kinase inhibitor 2A (CDKN2A) and V-Erb-B2 avian erythroblastic leukemia
      viral oncogene homolog-2, which are targeted by miR-125b, participate in the
      bladder cancer pathway. In conclusion, DE-miRNAs in bladder cancer tissue samples
      and DE-targeted genes, such as miR-106b and CDKN2A, which were identified in the
      present study, may provide the basis for targeted therapy for breast cancer and
      enhance understanding of its pathogenesis.

PMID- 25955760
TI  - Effect of High-Fidelity Simulation on Medical Students' Knowledge about Advanced
      Life Support: A Randomized Study.
AB  - High-fidelity simulation (HFS) is a learning method which has proven effective in
      medical education for technical and non-technical skills. However, its
      effectiveness for knowledge acquisition is less validated. We performed a
      randomized study with the primary aim of investigating whether HFS, in
      association with frontal lessons, would improve knowledge about advanced life
      support (ALS), in comparison to frontal lessons only among medical students. The
      secondary aims were to evaluate the effect of HFS on knowledge acquisition of
      different sections of ALS and personal knowledge perception. Participants
      answered a pre-test questionnaire consisting of a subjective (evaluating personal
      perception of knowledge) and an objective section (measuring level of knowledge)
      containing 100 questions about algorithms, technical skills, team working/early
      warning scores/communication strategies according to ALS guidelines. All students
      participated in 3 frontal lessons before being randomized in group S, undergoing
      a HFS session, and group C, receiving no further interventions. After 10 days
      from the end of each intervention, both groups answered a questionnaire (post
      test) with the same subjective section but a different objective one. The overall
      number of correct answers of the post-test was significantly higher in group S
      (mean 74.1, SD 11.2) than in group C (mean 65.5, SD 14.3), p = 0.0017, 95% C.I.
      3.34 - 13.9. A significantly higher number of correct answers was reported in
      group S than in group C for questions investigating knowledge of algorithms (p =
      0.0001; 95% C.I 2.22-5.99) and team working/early warning scores/communication
      strategies (p = 0.0060; 95% C.I 1.13-6.53). Students in group S showed a
      significantly higher score in the post-test subjective section (p = 0.0074). A
      lower proportion of students in group S confirmed their perception of knowledge
      compared to group C (p = 0.0079). HFS showed a beneficial effect on knowledge of
      ALS among medical students, especially for notions of algorithms and team
      working/early warning scores/communication. 

PMID- 25955763
TI  - Enhanced piezoelectric properties of vertically aligned single-crystalline NKN
      nano-rod arrays.
AB  - Piezoelectric materials capable of converting between mechanical and electrical
      energy have a great range of potential applications in micro- and nano-scale
      smart devices; however, their performance tends to be greatly degraded when
      reduced to a thin film due to the large clamping force by the substrate and
      surrounding materials. Herein, we report an effective method for synthesizing
      isolated piezoelectric nano-materials as means to relax the clamping force and
      recover original piezoelectric properties of the materials. Using this,
      environmentally friendly single-crystalline NaxK1-xNbO3 (NKN) piezoelectric nano
      rod arrays were successfully synthesized by conventional pulsed-laser deposition
      and demonstrated to have a remarkably enhanced piezoelectric performance. The
      shape of the nano-structure was also found to be easily manipulated by varying
      the energy conditions of the physical vapor. We anticipate that this work will
      provide a way to produce piezoelectric micro- and nano-devices suitable for
      practical application, and in doing so, open a new path for the development of
      complex metal-oxide nano-structures. 

PMID- 25955761
TI  - Comparison of overweight and obese military-dependent and civilian adolescent
      girls with loss-of-control eating.
AB  - OBJECTIVE: Limited data suggest that the children of U.S. service members may be
      at increased risk for disordered-eating. To date, no study has directly compared
      adolescent military-dependents to their civilian peers along measures of eating
      pathology and associated correlates. We, therefore, compared overweight and obese
      adolescent female military-dependents to their civilian counterparts along
      measures of eating-related pathology and psychosocial functioning. METHOD:
      Adolescent females with a BMI between the 85th and 97th percentiles and who
      reported loss-of-control eating completed interview and questionnaire assessments
      of eating-related and general psychopathology. RESULTS: Twenty-three military
      dependents and 105 civilians participated. Controlling for age, race, and BMI-z,
      military-dependents reported significantly more binge episodes per month (p <
      0.01), as well as greater eating-concern, shape-concern, and weight-concern (p's
      < 0.01) than civilians. Military-dependents also reported more severe depression
      (p < 0.05). DISCUSSION: Adolescent female military-dependents may be particularly
      vulnerable to disordered-eating compared with civilian peers. This potential
      vulnerability should be considered when assessing military-dependents.

PMID- 25955762
TI  - Biologically active and thermally stable polymeric Schiff base and its metal
      polychelates: Their synthesis and spectral aspects.
AB  - New metal polychelates of Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) obtained by
      the interaction of metal acetates with polymeric Schiff base containing
      formaldehyde and piperazine, have been investigated. Structural and spectroscopic
      properties have been evaluated by elemental analysis, FT-IR and (1)H-NMR.
      Geometry of the chelated polymers was confirmed by magnetic susceptibility
      measurements, UV-Visible spectroscopy and Electron Spin Resonance. The molecular
      weight of the polymer was determined by gel permeation chromatography (GPC).
      Thermogravimetric analysis indicated that metal polychelates were more thermally
      stable than their corresponding ligand. All compounds were screened for their
      antimicrobial activities against Escherichia coli, Staphylococcus aureus,
      Bacillus subtilis, (bacteria) and Candida albicans, Microsporum canis,
      Cryptococcus neoformans (fungi) by agar well diffusion method. Interestingly, the
      polymeric Schiff base was found to be antimicrobial in nature but less effective
      as compared to the metal polychelates. On the basis of thermal and antimicrobial
      behavior, these polymers hold potential applications as thermally resistant
      antimicrobial and antifouling coating materials as well as antimicrobial
      packaging materials. 

PMID- 25955764
TI  - Deletion of Fibrinogen-like Protein 2 (FGL-2), a Novel CD4+ CD25+ Treg Effector
      Molecule, Leads to Improved Control of Echinococcus multilocularis Infection in
      Mice.
AB  - BACKGROUND: The growth potential of the tumor-like Echinococcus multilocularis
      metacestode (causing alveolar echinococcosis, AE) is directly linked to the
      nature/function of the periparasitic host immune-mediated processes. We
      previously showed that Fibrinogen-like-protein 2 (FGL2), a novel CD4+CD25+ Treg
      effector molecule, was over-expressed in the liver of mice experimentally
      infected with E. multilocularis. However, little is known about its contribution
      to the control of this chronic helminth infection. METHODS/FINDINGS: Key
      parameters for infection outcome in E. multilocularis-infected fgl2-/- (AE-fgl2-/
      ) and wild type (AE-WT) mice at 1 and 4 month(s) post-infection were (i) parasite
      load (i. e. wet weight of parasitic metacestode tissue), and (ii) parasite cell
      proliferation as assessed by determining E. multilocularis 14-3-3 gene expression
      levels. Serum FGL2 levels were measured by ELISA. Spleen cells cultured with ConA
      for 48h or with E. multilocularis Vesicle Fluid (VF) for 96h were analyzed ex
      vivo and in-vitro. In addition, spleen cells from non-infected WT mice were
      cultured with rFGL2/anti-FGL2 or rIL-17A/anti-IL-17A for further functional
      studies. For Treg-immune-suppression-assays, purified CD4+CD25+ Treg suspensions
      were incubated with CD4+ effector T cells in the presence of ConA and irradiated
      spleen cells as APCs. Flow cytometry and qRT-PCR were used to assess Treg, Th17-,
      Th1-, Th2-type immune responses and maturation of dendritic cells. We showed that
      AE-fgl2-/- mice exhibited (as compared to AE-WT-animals) (a) a significantly
      lower parasite load with reduced proliferation activity, (b) an increased T cell
      proliferative response to ConA, (c) reduced Treg numbers and function, and (d) a
      persistent capacity of Th1 polarization and DC maturation. CONCLUSIONS: FGL2
      appears as one of the key players in immune regulatory processes favoring
      metacestode survival by promoting Treg cell activity and IL-17A production that
      contributes to FGL2-regulation. Prospectively, targeting FGL2 could be an option
      to develop an immunotherapy against AE and other chronic parasitic diseases.

PMID- 25955765
TI  - Transcriptome profiling of sugarcane roots in response to low potassium stress.
AB  - Sugarcane is the most important crop for supplying sugar. Due to its high
      biomass, sugarcane needs to absorb a large amount of potassium (K) throughout its
      lifecycle. In South China, a deficiency of K available in soil restricts the
      production of sugarcane. Increasing the tolerance of sugarcane to low-K will be
      an effective approach for improving survival of the crop in this area. However,
      there is little information regarding the mechanism of tolerance to low-K stress
      in sugarcane. In this study, a customized microarray was used to analyze the
      changes in the level of transcripts of sugarcane genes 8 h, 24 h and 72 h after
      exposure to low-K conditions. We identified a total of 4153 genes that were
      differentially expressed in at least one of the three time points. The number of
      genes responding to low-K stress at 72 h was almost 2-fold more than the numbers
      at 8 h and 24 h. Gene ontology (GO) analysis revealed that many genes involved in
      metabolic, developmental and biological regulatory processes displayed changes in
      the level of transcripts in response to low-K stress. Additionally, we detected
      differential expression of transcription factors, transporters, kinases,
      oxidative stress-related genes and genes in Ca+ and ethylene signaling pathways;
      these proteins might play crucial roles in improving the tolerance of sugarcane
      to low-K stress. The results of this study will help to better understand the
      molecular mechanisms of sugarcane tolerance to low-K. 

PMID- 25955766
TI  - Tunable Dirac Electron and Hole Self-Doping of Topological Insulators Induced by
      Stacking Defects.
AB  - Via density functional theory based calculations we show that self-doping of the
      surface Dirac cones in three-dimensional Bi2X3 (X = Se, Te) topological
      insulators can be tuned by controlling the sequence of stacking defects in the
      crystal. Twin boundaries inside the Bi2X3 bulk drive either n- or p-type self
      doping of the (0001) topological surface states, depending on the precise
      orientation of the twin. The surface doping may achieve values up to 300 meV and
      can be controlled by the number of defects and their relative position with
      respect to the surface. Its origin relies on the spontaneous polarization
      generated by the dipole moments associated with the lattice defects. Our findings
      open the route to the fabrication of Bi2X3 surfaces with tailored surface charge
      and spin densities in the absence of external electric fields. In addition, in a
      thin film geometry two-dimensional electron and hole Dirac gases with the same
      spin-helicity coexist at opposite surfaces. 

PMID- 25955767
TI  - Transient dynamics of magnetic Co-graphene systems.
AB  - We report the investigation of response time of spin resolved electron traversing
      through a magnetic Co-graphene nano-device. For this purpose, we calculate the
      transient current under a step-like upward pulse for this system from first
      principles using non-equilibrium Green's function (NEGF) formalism within the
      framework of density functional theory (DFT). In the absence of dephasing
      mechanisms, transient current shows a damped oscillatory behavior. The turn-on
      time of the magnetic Co-graphene nano-device was found to be around 5-20
      femtoseconds, while the relaxation time can reach several picoseconds due to the
      damped oscillation of transient current for both majority spin and minority spin.
      The response time was determined by the resonant states below the Fermi level,
      but does not depend on the chirality of graphene and the amplitude of pulse bias.
      Each resonant state contributes to the damped oscillation of transient current
      with the same frequency and different decay rates. The frequency of the
      oscillation is half the pulse bias and the decay rate equals the lifetime of the
      corresponding resonant state. When inelastic phase-relaxing scattering is
      considered, the long duration oscillatory behavior of the transient current is
      suppressed and the relaxation time is reduced to hundreds of femtoseconds. 

PMID- 25955768
TI  - Neurogenic pulmonary edema following Cryptococcal meningoencephalitis associated
      with HIV infection.
AB  - Neurogenic pulmonary edema (NPE) is a clinical syndrome characterized by the
      acute onset of pulmonary edema following a significant central nervous system
      insult. Only a few cases of NPE after Cryptococcal meningitis have been reported.
      We report a case of NPE following Cryptococcal meningoencephalitis. A 40-year-old
      man with no medical history was hospitalized for disturbance of consciousness.
      Blood glucose level was 124 mg/dL. Non-contrast head computed tomography showed
      no abnormalities. Lumbar puncture revealed a pressure of over 300 mm H2 O and
      cerebrospinal fluid (CSF) confirmed a white blood cell count of 65/mm(3) . The
      CSF glucose level was 0 mg/dL. The patient was empirically started on treatment
      for presumptive bacterial and viral meningitis. Four days after, the patient died
      in a sudden severe pulmonary edema. Autopsy was performed. We found at autopsy a
      brain edema with small hemorrhage of the right basal ganglia, severe pulmonary
      edema and mild cardiomegaly. Histologically, dilated Virchow-Robin spaces,
      crowded with Cryptococci were observed. In the right basal ganglia, Virchow-Robin
      spaces were destroyed with hemorrhage and Cryptococci spread to parenchyma of the
      brain. No inflammatory reaction of the lung was seen. Finally, acute pulmonary
      edema in this case was diagnosed as NPE following Cryptococcal
      meningoencephalitis. After autopsy, we found that he was positive for serum
      antibodies to human immunodeficiency virus.

PMID- 25955769
TI  - Surfaces for competitive selective bacterial capture from protein solutions.
AB  - Active surfaces that form the basis for bacterial sensors for threat detection,
      food safety, or certain diagnostic applications rely on bacterial adhesion.
      However, bacteria capture from complex fluids on the active surfaces can be
      reduced by the competing adsorption of proteins and other large molecules. Such
      adsorption can also interfere with device performance. As a result, multiple
      upstream processing steps are frequently employed to separate macromolecules from
      any cells, which remain in the buffer. Here, we present an economical approach to
      capture bacteria, without competitive adsorption by proteins, on engineered
      surfaces that do not employ biomolecular recognition, antibodies, or other
      molecules with engineered sequences. The surfaces are based on polyethylene
      glycol (PEG) brushes that, on their own, repel both proteins and bacteria. These
      PEG brushes backfill the surface around sparsely adsorbed cationic polymer coils
      (here, poly-L-lysine (PLL)). The PLL coils are effectively embedded within the
      brush and produce locally cationic nanoscale regions that attract negatively
      charged regions of proteins or cells against the steric background repulsion from
      the PEG brush. By carefully designing the surfaces to include just enough PLL to
      capture bacteria, but not enough to capture proteins, we achieve sharp
      selectivity where S. aureus is captured from albumin- or fibrinogen-containing
      solutions, but free albumin or fibrinogen molecules are rejected from the
      surface. Bacterial adhesion on these surfaces is not reduced by competitive
      protein adsorption, in contrast to performance of more uniformly cationic
      surfaces. Also, protein adsorption to the bacteria does not interfere with
      capture, at least for the case of S. aureus, to which fibrinogen binds through a
      specific receptor.

PMID- 25955770
TI  - "An impediment to living life": why and how should we measure stiffness in
      polymyalgia rheumatica?
AB  - OBJECTIVES: To explore patients' concepts of stiffness in polymyalgia rheumatica
      (PMR), and how they think stiffness should be measured. METHODS: Eight focus
      groups were held at three centres involving 50 patients with current/previous
      PMR. Each group had at least one facilitator and one rapporteur making field
      notes. An interview schedule was used to stimulate discussion. Interviews were
      recorded, transcribed and analysed using an inductive thematic approach. RESULTS:
      Major themes identified were: symptoms: pain, stiffness and fatigue; functional
      impact; impact on daily schedule; and approaches to measurement. The common
      subtheme for the experience of stiffness was "difficulty in moving", and usually
      considered as distinct from the experience of pain, albeit with a variable
      overlap. Some participants felt stiffness was the "overwhelming" symptom, in that
      it prevented them carrying out "fundamental activities" and "generally living
      life". Diurnal variation in stiffness was generally described in relation to the
      daily schedule but was not the same as stiffness severity. Some participants
      suggested measuring stiffness using a numeric rating scale or a Likert scale,
      while others felt that it was more relevant and straightforward to measure
      difficulty in performing everyday activities rather than about stiffness itself.
      CONCLUSIONS: A conceptual model of stiffness in PMR is presented where stiffness
      is an important part of the patient experience and impacts on their ability to
      live their lives. Stiffness is closely related to function and often regarded as
      interchangeable with pain. From the patients' perspective, visual analogue scales
      measuring pain and stiffness were not the most useful method for reporting
      stiffness; participants preferred numerical rating scales, or assessments of
      function to reflect how stiffness impacts on their daily lives. Assessing
      function may be a pragmatic solution to difficulties in quantifying stiffness.

PMID- 25955772
TI  - Correction: A rational computational study of surface defect-mediated
      stabilization of low-dimensional Pt nanostructures on TiN(100).

PMID- 25955771
TI  - Assessment of pulsed electromagnetic field therapy with Serum YKL-40 and
      ultrasonography in patients with knee osteoarthritis.
AB  - AIM: The use of biomarkers of osteoarthritis (OA) have potential for early
      diagnosis, evaluation of disease severity and monitoring treatment. Serum and
      synovial fluid YKL-40 levels are increased in severe knee OA. Pulsed
      electromagnetic field (PEMF) therapy is a novel treatment method for OA. However,
      studies evaluating the PEMF therapy in treatment of knee OA revealed conflicting
      results. This study was conducted to objectively assess the effect of PEMF
      therapy in patients with knee OA, by using ultrasonographic measurements and a
      novel biomarker, YKL-40. METHODS: Forty patients were randomized into two
      treatment groups. Both groups received conventional physical therapy, while Group
      1 received additional PEMF therapy. The patients were asked to rate their pain on
      a visual analogue scale (VAS) and complete a Western Ontario and McMaster
      Universities Osteoarthritis Index (WOMAC) questionnaire. Serum YKL-40 levels were
      measured, and knee effusion and cartilage degeneration level were evaluated with
      ultrasonography before and after treatment. RESULTS: Pre-treatment YKL-40 level
      was correlated with WOMAC pain subscale (P = 0.032, r = 0.339). VAS and WOMAC
      scores significantly improved in both treatment groups (P < 0.05). The effusion
      in the right knee significantly decreased in Group 1. The change in YKL-40 level
      was not correlated with the change in VAS, WOMAC scores and knee effusion.
      CONCLUSION: This study revealed that adjuvant PEMF therapy has no additional
      effect on pain in patients with knee OA. Serum YKL-40 level seems to be unuseful
      for monitoring the treatment in knee OA.

PMID- 25955773
TI  - Emergence of enterovirus D68 in Denmark, June 2014 to February 2015.
AB  - From June 2014 through February 2015, respiratory samples from 130 Danish
      patients were screened for enterovirus D68 (EV-D68). Fourteen EV-D68 cases were
      detected, of which 12 presented with respiratory symptoms, and eight had known
      underlying disease. The median age of EV-D68 cases was three years (interquartile
      range: 0-30 years). Acute flaccid paralysis (AFP) was not detected although
      Danish EV-D68 strains showed > 98% nt identity with EV-D68-strains from AFP cases
      from the United States and France.

PMID- 25955774
TI  - Chikungunya outbreak in Montpellier, France, September to October 2014.
AB  - In October 2014, an outbreak of 12 autochthonous chikungunya cases, 11 confirmed
      and 1 probable, was detected in a district of Montpellier, a town in the south of
      France colonised by the vector Aedes albopictus since 2010. A case returning from
      Cameroon living in the affected district was identified as the primary case. The
      epidemiological investigations and the repeated vector control treatments
      performed in the area and around places frequented by cases helped to contain the
      outbreak. In 2014, the chikungunya and dengue surveillance system in mainland
      France was challenged by numerous imported cases due to the chikungunya epidemic
      ongoing in the Caribbean Islands. This first significant outbreak of chikungunya
      in Europe since the 2007 Italian epidemic, however, was due to an East Central
      South African (ECSA) strain, imported by a traveller returning from West Africa.
      Important lessons were learned from this episode, which reminds us that the
      threat of a chikungunya epidemic in southern Europe is real.

PMID- 25955775
TI  - Cheese-related listeriosis outbreak, Portugal, March 2009 to February 2012.
AB  - In Portugal, listeriosis has been notifiable since April 2014, but there is no
      active surveillance programme for the disease. A retrospective study involving 25
      national hospitals led to the detection of an outbreak that occurred between
      March 2009 and February 2012. The amount of time between the start of the
      outbreak and its detection was 16 months. Of the 30 cases of listeriosis
      reported, 27 were in the Lisbon and Vale do Tejo region. Two cases were
      maternal/neonatal infections and one resulted in fetal loss. The mean age of the
      non-maternal/neonatal cases was 59 years (standard deviation: 17); 13 cases were
      more than 65 years old. The case fatality rate was 36.7%. All cases were caused
      by molecular serogroup IVb isolates indistinguishable by pulsed-field gel
      electrophoresis and ribotype profiles. Collaborative investigations with the
      national health and food safety authorities identified cheese as the probable
      source of infection, traced to a processing plant. The magnitude of this
      outbreak, the first reported food-borne listeriosis outbreak in Portugal,
      highlights the importance of having an effective listeriosis surveillance system
      in place for early detection and resolution of outbreaks, as well as the need for
      a process for the prompt submission of Listeria monocytogenes isolates for
      routine laboratory typing.

PMID- 25955776
TI  - Monitoring meticillin resistant Staphylococcus aureus and its spread in
      Copenhagen, Denmark, 2013, through routine whole genome sequencing.
AB  - Typing of meticillin resistant Staphylococcus aureus (MRSA) by whole genome
      sequencing (WGS) is performed routinely in Copenhagen since January 2013. We
      describe the relatedness, based on WGS data and epidemiological data, of 341 MRSA
      isolates. These comprised all MRSA (n = 300) identified in Copenhagen in the
      first five months of 2013. Moreover, because MRSA of staphylococcal protein A
      (spa)-type 304 (t304), sequence type (ST) 6 had been associated with a continuous
      neonatal ward outbreak in Copenhagen starting in 2011, 41 t304 isolates collected
      in the city between 2010 and 2012 were also included. Isolates from 2013 found to
      be of t304, ST6 (n=14) were compared to the 41 earlier isolates. In the study,
      isolates of clonal complex (CC) 22 were examined in detail, as this CC has been
      shown to include the hospital-acquired epidemic MRSA (EMRSA-15) clone. Finally,
      all MRSA ST80 were also further analysed, as representatives of an important
      community-acquired MRSA in Europe. Overall the analysis identified 85 spa-types
      and 35 STs from 17 CCs. WGS confirmed the relatedness of epidemiologically linked
      t304 neonatal outbreak isolates. Several non-outbreak related patients had
      isolates closely related to the neonatal isolates suggesting unrecognised
      community chains of transmission and insufficient epidemiological data. Only four
      CC22 isolates were related to EMRSA-15. No community spread was observed among
      the 13 ST80 isolates. WGS successfully replaced conventional typing and added
      information to epidemiological surveillance. Creation of a MRSA database allows
      clustering of isolates based on single nucleotide polymorphism (SNP) calling and
      has improved our understanding of MRSA transmission.

PMID- 25955778
TI  - Erratum for Euro Surveill. 2015;20(15).

PMID- 25955779
TI  - Addendum for Euro Surveill. 2014;19(40).

PMID- 25955780
TI  - Authors correction for Euro Surveill. 2014;19(40).

PMID- 25955781
TI  - Editorial note for Euro Surveill. 2014;19(40).

PMID- 25955783
TI  - Emergent user behavior on Twitter modelled by a stochastic differential equation.
AB  - Data from the social-media site, Twitter, is used to study the fluctuations in
      tweet rates of brand names. The tweet rates are the result of a strongly
      correlated user behavior, which leads to bursty collective dynamics with a
      characteristic 1/f noise. Here we use the aggregated "user interest" in a brand
      name to model collective human dynamics by a stochastic differential equation
      with multiplicative noise. The model is supported by a detailed analysis of the
      tweet rate fluctuations and it reproduces both the exact bursty dynamics found in
      the data and the 1/f noise. 

PMID- 25955782
TI  - Determination of influence of food intake after a single oral dose of mosapride
      in beagle dogs using nonlinear mixed effect modeling.
AB  - The objective of this study was to describe the population pharmacokinetics (PK)
      of mosapride under fasting and fed conditions. A single 5-mg oral dose of
      mosapride was administered to fasted (n = 15) and fed (n = 12) beagle dogs.
      Plasma concentrations of mosapride were subsequently measured by liquid
      chromatography-tandem mass spectrometry. Data were analyzed using modeling
      approaches with the NONMEM 7.2 software. A one-compartment open PK model
      utilizing model event time (MTIME) with first-order absorption and first-order
      elimination was found to be more appropriate than all other PK models tested. The
      absorption rate constants of mosapride were significantly decreased under fed
      conditions, compared to fasting conditions. The observed bootstrap medians of PK
      parameters were generally consistent with the corresponding population mean
      estimates. Furthermore, with the exception of some mosapride concentrations, most
      of observed data fell into the range of the 5th and 95th percentiles of the
      simulated values. Overall, the final model was able to describe the observed
      mosapride concentrations reasonably well. These findings suggest that food intake
      affects both the rate and extent of absorption of mosapride and that the
      pharmacological effect of mosapride can differ significantly depending on food
      intake. 

PMID- 25955784
TI  - Association between interleukin-10-3575T>A (rs1800890) polymorphism and cancer
      risk.
AB  - BACKGROUND: Previous studies investigated the associations of interleukin-10 (IL
      10) polymorphisms with different types of cancer, indicating an influence on
      cancer risk. IL-10-3575T>A (rs1800890) has been studied concerning a potential
      implication in terms of some cancer site risks, but the results from single
      studies are contradictory. METHODS: Eligible articles were identified by a search
      of the PubMed, Web of Science, and Chinese National Knowledge Infrastructure
      (CNKI) databases until November 30, 2014. Crude odds ratios (ORs) with 95%
      confidence intervals (CIs) were used to evaluate the cancer risk by cancer sites,
      ethnicity, and other study features. RESULTS: We identified 15 published studies
      to research the link of the IL-10-3575T>A polymorphism with cancer risk. Our meta
      analysis indicated that the IL-10-3575T>A polymorphism has a significant
      association with decreased melanoma risk in the heterozygote model (OR=0.67, 95%
      CI=0.49-0.92, p=0.02) and dominant model (OR=0.70, 95% CI=0.52-0.95, p=0.01), but
      increased diffuse large B-cell lymphoma (DLBCL) risk in all the different genetic
      models. CONCLUSION: Our analysis suggests that the IL-10-3575T>A mutation may
      associate with melanoma and DLBCL and exert a differential effect in different
      cancer sites. However, other factors may influence the association, and large
      scale multicenter with adequate methodological quality studies are needed to
      confirm the impact on cancer susceptibility.

PMID- 25955786
TI  - Local minimum in fragility for trehalose/glycerol mixtures: implications for
      biopharmaceutical stabilization.
AB  - Approximately a decade ago it was observed that adding a small amount (5 wt %) of
      glycerol to trehalose could substantially improve the stability of enzymes stored
      in these glasses even though the final glass transition temperature (Tg) was
      reduced by ~20 K. This finding inspired great interest in the fast dynamics of
      dehydrated trehalose/glycerol mixtures, leading to the observation that
      suppression of fast dynamics was optimal in the presence of ~5 wt % of glycerol.
      It was also recognized that the fast dynamics should, in theory, be related to
      the fragility of these glass formers, but experimental confirmation of this
      hypothesis has been lacking for trehalose/glycerol mixtures or any other mixtures
      of this nature. In the present study a dynamic mechanical analyzer (DMA) was used
      to determine both the Tg and the kinetic fragility index (m) of
      trehalose/glycerol mixtures within the mass fraction range of 80-100 wt % of
      trehalose. It was found that the fragility index correlated with the mass
      fraction of trehalose in a nonmonotonic manner, with a local minimum between 87.5
      and 95 wt % of trehalose, whereas the composition dependence of Tg was found to
      follow a Gordon-Taylor-like relationship, with no local minimum. The composition
      of 5-12.5 wt % glycerol in trehalose thus yielded a matrix that maximized the
      strong glass-forming contribution of glycerol, while minimizing its Tg lowering
      effect. This quantitative evidence supports speculation about the fragility
      characteristics of these mixtures that has been ongoing for the past decade. The
      DMA-based Tg and fragility determination method developed in this study
      represents a new approach for identifying optimal compositions for preservation
      of biologics. 

PMID- 25955785
TI  - The role of Epstein-Barr virus-encoded microRNA BART7 status of resection margins
      in the prediction of local recurrence after salvage nasopharyngectomy for
      recurrent nasopharyngeal carcinoma.
AB  - BACKGROUND: Local recurrence is the major cause of treatment failure in patients
      who undergo surgical salvage of recurrent nasopharyngeal carcinoma (NPC) after
      radiotherapy. The authors investigated the role of Epstein-Barr virus (EBV)
      encoded Bam HI-A rightward transcript 7 microRNA (BART7) status in resection
      margins in the identification of a subgroup of patients who may benefit from
      adjuvant reradiation after surgery. METHODS: One hundred two consecutive patients
      who had histologically clear resection margins after undergoing nasopharyngectomy
      for recurrent NPC were studied. The status of EBV microRNA BART7 in resection
      margins was investigated and correlated with the pattern of subsequent disease
      recurrence. RESULTS: After a median follow-up of 64 months, 20 patients (19.6%)
      developed local recurrence after surgery despite histologically uninvolved
      margins. The risk of local recurrence in patients with histologically close (<5
      mm) and clear (>=5 mm) margins was 31.6% and 12.5%, respectively. In patients
      with clear histologic margins, those with margins that were positive for EBV
      microRNA BART7 has a significantly higher chance of developing local tumor
      recurrence (P = .016) than those with negative molecular margins. The difference
      was not significant when the histologic clearance at the resection margins was <5
      mm. CONCLUSIONS: Tissue EBV microRNA BART7 is useful for identifying a subgroup
      of patients with histologically clear margins who are at increased risk of
      subsequent local tumor recurrence. Postoperative adjuvant treatment is warranted
      for these patients.

PMID- 25955788
TI  - Impaired Inhibitory Force Feedback in Fixed Dystonia.
AB  - Complex regional pain syndrome (CRPS) is a multifactorial disorder associated
      with an aberrant host response to tissue injury. About 25% of CRPS patients
      suffer poorly understood involuntary sustained muscle contractions associated
      with dysfunctional reflexes that result in abnormal postures (fixed dystonia). A
      recent modeling study simulated fixed dystonia (FD) caused by aberrant force
      feedback. The current study aims to validate this hypothesis by experimentally
      recording the modulation of reflexive force feedback in patients with FD. CRPS
      patients with and without FD, patients with FD but without CRPS, as well as
      healthy controls participated in the experiment. Three task instructions and
      three perturbation characteristics were used to evoke a wide range of responses
      to force perturbations. During position tasks ("maintain posture"), healthy
      subjects as well as patients resisted the perturbations, becoming more stiff than
      when being relaxed (i.e., the relax task). Healthy subjects and CRPS patients
      without FD were both more compliant during force tasks ("maintain force") than
      during relax tasks, meaning they actively gave way to the imposed forces.
      Remarkably, the patients with FD failed to do so. A neuromuscular model was
      fitted to the experimental data to separate the distinct contributions of
      position, velocity and force feedback, as well as co-contraction to the motor
      behavior. The neuromuscular modeling indicated that inhibitory force feedback is
      deregulated in patients with FD, for both CRPS and non-CRPS patients. From
      previously published simulation results and the present experimental study, it is
      concluded that aberrant force feedback plays a role in fixed dystonia. 

PMID- 25955787
TI  - Toxin acidic residue evolutionary function-guided design of de novo peptide drugs
      for the immunotherapeutic target, the Kv1.3 channel.
AB  - During the long-term evolution of animal toxins acting on potassium channels, the
      acidic residues can orientate the toxin binding interfaces by adjusting the
      molecular polarity. Based on the evolutionary function of toxin acidic residues,
      de novo peptide drugs with distinct binding interfaces were designed for the
      immunotherapeutic target, the Kv1.3 channel. Using a natural basic toxin, BmKTX,
      as a template, which contains 2 acidic residues (Asp19 and Asp33), we engineered
      two new peptides BmKTX-19 with 1 acidic residue (Asp33), and BmKTX-196 with 2
      acidic residues (Asp6 and Asp33) through only adjusting acidic residue
      distribution for reorientation of BmKTX binding interface. Pharmacological
      experiments indicated that BmKTX-19 and BmKTX-196 peptides were specific
      inhibitors of the Kv1.3 channel and effectively suppressed cytokine secretion. In
      addition to the structural similarity between the designed and native peptides,
      both experimental alanine-scanning mutagenesis and computational simulation
      further indicated that the binding interface of wild-type BmKTX was successfully
      reoriented in BmKTX-19 and BmKTX-196, which adopted distinct toxin surfaces as
      binding interfaces. Together, these findings indicate not only the promising
      prospect of BmKTX-19 and BmKTX-196 as drug candidates but also the desirable
      feasibility of the evolution-guided peptide drug design for discovering numerous
      peptide drugs for the Kv1.3 channel. 

PMID- 25955789
TI  - Variable Cadence Walking and Ground Adaptive Standing With a Powered Ankle
      Prosthesis.
AB  - This paper describes a control approach that provides walking and standing
      functionality for a powered ankle prosthesis, and demonstrates the efficacy of
      the approach in experiments with a unilateral transtibial amputee subject. Both
      controllers incorporate a finite-state structure that emulates healthy ankle
      joint behavior via a series of piecewise passive impedance functions. The walking
      controller additionally modifies impedance parameters based on estimated cadence,
      while the standing controller modulates the ankle equilibrium angle in order to
      adapt to the ground slope and user posture, and the supervisory controller
      selects between the walking and standing controllers. The system is shown to
      reproduce several essential biomechanical features of the healthy joint during
      walking, particularly relative to a passive prosthesis, and is shown to adapt to
      various cadences. The system is also shown to adapt to slopes over a range of +/
      15 degrees , providing support to the user, as validated by quasi-static
      stiffness measurements recorded by the prosthesis. The subject is shown to place
      more weight on the powered prosthesis than on his passive prosthesis when
      standing on sloped surfaces, particularly at angles of 10 degrees  or greater.
      The authors also demonstrated that the prosthesis typically began providing
      support within 1 s of initial ground contact. Further, the supervisory controller
      was shown to effectively switch between walking and standing, as well as
      determine ground slope just prior to the transition from the standing controller
      to the walking controller, where the estimated ground slope was accurate to
      within 1.25 degrees  for all trials.

PMID- 25955790
TI  - Analysis of changes in microRNA expression profiles in response to the troxerutin
      mediated antioxidant effect in human dermal papilla cells.
AB  - Dermal papilla (DP) cells function as important regulators of the hair growth
      cycle. The loss of these cells is a primary cause of diseases characterized by
      hair loss, including alopecia, and evidence has revealed significantly increased
      levels of reactive oxygen species (ROS) in hair tissue and DP cells in the
      balding population. In the present study, troxerutin, a flavonoid derivative of
      rutin, was demonstrated to have a protective effect against H2O2-mediated
      cellular damage in human DP (HDP) cells. Biochemical assays revealed that
      pretreatment with troxerutin exerted a protective effect against H2O2-induced
      loss of cell viability and H2O2-induced cell death. Further experiments confirmed
      that troxerutin inhibited the H2O2-induced production of ROS and upregulation of
      senescence-associated beta-galactosidase activity. Using microRNA (miRNA)
      microarrays, the present study identified 24 miRNAs, which were differentially
      expressed in the troxerutin-pretreated, H2O2-treated HDP cells. Subsequent
      prediction using bioinformatics analysis revealed that the altered miRNAs were
      functionally involved in several cell signaling pathways, including the mitogen
      activated protein kinase and WNT pathways. Overall, these results indicated that
      ROS-mediated cellular damage was inhibited by troxerutin and suggested that the
      use of troxerutin may be an effective approach in the treatment of alopecia.

PMID- 25955791
TI  - Computing membrane-AQP5-phosphatidylserine binding affinities with hybrid steered
      molecular dynamics approach.
AB  - In order to elucidate how phosphatidylserine (PS6) interacts with AQP5 in a cell
      membrane, we developed a hybrid steered molecular dynamics (hSMD) method that
      involved: (1) Simultaneously steering two centers of mass of two selected
      segments of the ligand, and (2) equilibrating the ligand-protein complex with and
      without biasing the system. Validating hSMD, we first studied vascular
      endothelial growth factor receptor 1 (VEGFR1) in complex with N-(4-Chlorophenyl)
      2-((pyridin-4-ylmethyl)amino)benzamide (8ST), for which the binding energy is
      known from in vitro experiments. In this study, our computed binding energy well
      agreed with the experimental value. Knowing the accuracy of this hSMD method, we
      applied it to the AQP5-lipid-bilayer system to answer an outstanding question
      relevant to AQP5's physiological function: Will the PS6, a lipid having a single
      long hydrocarbon tail that was found in the central pore of the AQP5 tetramer
      crystal, actually bind to and inhibit AQP5's central pore under near
      physiological conditions, namely, when AQP5 tetramer is embedded in a lipid
      bilayer? We found, in silico, using the CHARMM 36 force field, that binding PS6
      to AQP5 was a factor of 3 million weaker than "binding" it in the lipid bilayer.
      This suggests that AQP5's central pore will not be inhibited by PS6 or a similar
      lipid in a physiological environment. 

PMID- 25955792
TI  - A-D-A Type Small Molecules Based on Boron Dipyrromethene for Solution-Processed
      Organic Solar Cells.
AB  - The unique properties of boron dipyrromethene (BODIPY) dyes including facile
      synthesis, high absorption coefficients, and delocalized molecular orbitals as
      well as excellent photochemical and thermal stability, make them promising as
      materials for organic solar cells. Accordingly, in this study three A-D-A
      structural small molecules of BDTT-BODIPY, FL-BODIPY, and TT-BODIPY have been
      synthesized, in which two BODIPY acceptor units are symmetrically conjugated to
      4,8-bis(5-(2-ethylhexyl) thiophen-2-yl)benzo[1,2-b:4,5-b]dithiophene (BDTT), 9,9
      dioctyl-9H-fluorene (FL), and thieno[3,2-b]thiophene (TT) donor cores,
      respectively. The manipulation of the structural parameters significantly
      improves the performances of the BHJ OSCs, which show power conversion
      efficiencies of 4.75%, 1.51%, and 1.67% based on [6,6]-phenyl C71 -butyric acid
      methyl ester (PC71 BM) as the acceptor material and BDTT-BODIPY, FL-BODIPY, and
      TT-BODIPY as the donor materials, respectively.

PMID- 25955793
TI  - Enzymatic bioconjugation of nanoparticles: developing specificity and control.
AB  - Nanoparticles are finding increasing roles in biotechnology for applications as
      contrast agents, probes, sensors, therapeutics and increasingly new value-added
      hybrid materials such as molecular logic devices. In most cases these materials
      must be conjugated to different types of biologicals such as proteins or DNA to
      accomplish this. However, most traditional methods of bioconjugation result in
      heterogeneous attachment and loss of activity. Bioorthogonal chemistries and in
      particular enzymatic labeling chemistries offer new strategies for catalyzing
      specific biomolecular attachment. We highlight current enzymatic labeling methods
      available for bioconjugating nanoparticles, some materials they have been used
      with, and how the resulting bioconjugates were applied. A discussion of the
      benefits and remaining issues associated with this type of bioconjugation
      chemistry and a brief perspective on how this field will develop is also
      provided. 

PMID- 25955794
TI  - MicroRNA-216a inhibits the growth and metastasis of oral squamous cell carcinoma
      by targeting eukaryotic translation initiation factor 4B.
AB  - There is increasing evidence to suggest that microRNAs (miRNAs; miRs) are
      involved in the development of oral squamous cell carcinoma (OSCC). miR-216a has
      been identified as being involved in tumorigenesis, however, the mechanisms of
      miR-216a in various types of cancer, either as a tumor suppressor or as an
      oncogenic miRNA, and the specific regulatory role of miR-216a in OSCC remain to
      be elucidated. The present study demonstrated that the expression of miR-216a was
      significantly reduced in OSCC tissues and cell lines. Overexpression of miR-216a
      significantly suppressed the proliferation, colony formation, migration and
      invasion of the OSCC cells. In addition, eukaryotic translation initiation factor
      4B (EIF4B) was identified as a direct target of miR-216a, which was observed to
      be upregulated in the OSCC tissues. Furthermore, overexpression of EIF4B
      significantly attenuated the antitumor effect of miR-216a, and a negative
      correlation was observed between miR-216a and EIF4B in the OSCC tissues. Taken
      together, these findings indicated that miR-216a has a suppressive role in OSCC
      cells by directly targeting EIF4B, and may function as a potential prognostic
      biomarker and novel therapeutic target.

PMID- 25955795
TI  - MicroRNA-29c targets beta-site amyloid precursor protein-cleaving enzyme 1 and
      has a neuroprotective role in vitro and in vivo.
AB  - Alzheimer's disease (AD), characterized by beta-amyloid deposition and
      neurodegeneration, is the most common cause of dementia worldwide. Emerging
      evidence suggests that ectopic expression of micro (mi)RNAs is involved in the
      pathogenesis of AD. There is increasing evidence that miRNAs expressed in the
      brain are involved in neuronal development, survival and apoptosis. The
      expression of beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) is
      regulated by dysregulated miRNAs in the brain. The present study determined the
      expression levels of the miRNA-29 (miR-29) family in peripheral blood samples of
      patients with AD and demonstrated a marked decrease in the expression of miR-29c
      compared with age-matched controls. In addition, a significant increase in the
      expression of BACE1 was observed in the peripheral blood of patients with AD.
      Correlation analysis revealed that the expression of miR-29c was negatively
      correlated with the protein expression of BACE1 in the peripheral blood samples
      from patients with AD. The present study also investigated the role of miR-29 on
      hippocampal neurons in vitro and in vivo. The results demonstrated that the
      upregulation of miR-29c promoted learning and memory behaviors in SAMP8 mice, at
      least partially, by increasing the activity of protein kinase A/cAMP response
      element-binding protein, involved in neuroprotection. This evidence suggested
      that miR-29c may be a promising potential therapeutic target against AD.

PMID- 25955796
TI  - Peptidyl-oligonucleotide conjugates demonstrate efficient cleavage of RNA in a
      sequence-specific manner.
AB  - Described here is a new class of peptidyl-oligonucleotide conjugates (POCs) which
      show efficient cleavage of a target RNA in a sequence-specific manner. Through
      phosphoramidate attachment of a 17-mer TPsiC-targeting oligonucleotide to
      amphiphilic peptide sequences containing leucine, arginine, and glycine, zero
      linker conjugates are created which exhibit targeted phosphodiester cleavage
      under physiological conditions. tRNA(Phe) from brewer's yeast was used as a model
      target sequence in order to probe different structural variants of POCs in terms
      of selective TPsiC-arm directed cleavage. Almost quantitative (97-100%) sequence
      specific tRNA cleavage is observed for several POCs over a 24 h period with a
      reaction half-life of less than 1 h. Nontargeted cleavage of tRNA(Phe) or HIV-1
      RNA is absent. Structure-activity relationships reveal that removal of the
      peptide's central glycine residue significantly decreases tRNA cleavage activity;
      however, this can be entirely restored through replacement of the peptide's C
      terminal carboxylic acid group with the carboxamide functionality. Truncation of
      the catalytic peptide also has a detrimental effect on POC activity. Based on the
      encouraging results presented, POCs could be further developed with the aim of
      creating useful tools for molecular biology or novel therapeutics targeting
      specific messenger, miRNA, and genomic viral RNA sequences. 

PMID- 25955797
TI  - Ski prevents TGF-beta-induced EMT and cell invasion by repressing SMAD-dependent
      signaling in non-small cell lung cancer.
AB  - Epithelial-mesenchymal transition (EMT) is a key event in cancer metastasis,
      which confers cancer cells with increased motility and invasiveness, and EMT is
      characterized by loss of epithelial marker E-cadherin and gain of mesenchymal
      marker N-cadherin. Transforming growth factor-beta (TGF-beta) signaling is a
      crucial inducer of EMT in various types of cancer. Ski is an important negative
      regulator of TGF-beta signaling, which interacts with SMADs to repress TGF-beta
      signaling activity. Although there is accumulating evidence that Ski functions as
      a promoter or suppressor in human types of cancer, the molecular mechanisms by
      which Ski affects TGF-beta-induced EMT and invasion in non-small cell lung cancer
      (NSCLC) are not largely elucidated. In the present study, we investigated the
      mechanistic role of Ski in NSCLC metastasis. Ski was significantly reduced in
      metastatic NSCLC cells or tissues when compared with non-metastatic NSCLC cells
      or tissues. Moreover, following TGF-beta stimulation Ski-silenced A549 cells had
      more significant features of EMT and a higher invasive activity when compared
      with A549 cells overexpressing Ski. Mechanistically, Ski-silenced and
      overexpressed A549 cells showed an increase and a reduction in the SMAD3
      phosphorylation level, respectively. This was supported by plasminogen activator
      inhibitor-1 (PAI-1) promoter activity obtained in Ski-silenced and overexpressed
      A549 cells. However, after treatment of SIS3 (inhibitor of SMAD3 phosphorylation)
      followed by TGF-beta1 stimulation, we did not observe any effect of Ski on TGF
      beta-induced EMT, and invasion in Ski-silenced and overexpressed A549 cells. In
      conclusion, our findings suggest that Ski represses TGF-beta-induced EMT and
      invasion by inhibiting SMAD-dependent signaling in NSCLC.

PMID- 25955799
TI  - Targeting hypoxia-inducible factor 1 to stimulate tissue vascularization.
AB  - When tissue perfusion is impaired, the resulting reduction in O2 availability
      activates hypoxia-inducible factor 1 (HIF-1), which mediates increased
      transcription of genes encoding multiple angiogenic factors including vascular
      endothelial growth factor, stromal-derived factor 1, placental growth factor, and
      angiopoietins, leading to the mobilization of bone marrow-derived angiogenic
      cells, increased angiogenesis, and arterial remodeling. These HIF- 1-dependent
      responses are impaired by aging or loss of function mutations at the locus
      encoding the HIF-1alpha subunit. in mouse models of limb ischemia and lung
      transplant rejection, the augmentation of HIF-1 activity by gene therapy or
      chemical inducers was associated with maintenance of tissue perfusion that
      prevented limb amputation and allograft rejection, respectively. Thus, targeting
      HIF-1 may be of therapeutic benefit in these clinical contexts and others in
      which impaired tissue perfusion plays a role in disease pathogenesis. 

PMID- 25955800
TI  - Craniovertebral junction instability as an extension of cocaine-induced midline
      destructive lesions: case report.
AB  - With the increasingly widespread illicit use of cocaine, a broad spectrum of
      clinical pathologies related to this form of drug abuse is emerging. The most
      frequently used method of administration of powdered cocaine is intranasal
      inhalation, or "snorting." Consequently, adverse effects of cocaine on the nasal
      tract are common. Habitual nasal insufflations of cocaine can cause mucosal
      lesions. If cocaine use becomes chronic and compulsive, progressive damage of the
      mucosa and perichondrium leads to ischemic necrosis of the septal cartilage and
      perforation of the nasal septum. Occasionally, cocaine-induced lesions cause
      extensive destruction of the osteocartilaginous structures of the nose, sinuses,
      and palate and can mimic other diseases such as tumors, infections, and
      immunological diseases. In the literature currently available, involvement of the
      craniovertebral junction in the cocaine-induced midline destructive lesions
      (CIMDLs) has never been reported. The present case concerns a 44-year-old man who
      presented with long-standing symptoms including nasal obstruction, epistaxis,
      dysphagia, nasal reflux, and severe neck pain. A diagnosis of CIMDL was made in
      light of the patient's history and the findings on physical and endoscopic
      examinations, imaging studies, and laboratory testing. Involvement of the
      craniovertebral junction in the destructive process was evident. For
      neurosurgical treatment, the authors considered the high grade of atlantoaxial
      instability, the poorly understood cocaine-induced lesions of the spine and their
      potential evolution overtime, as well as cocaine abusers' poor compliance. The
      patient underwent posterior craniovertebral fixation. Understanding, classifying,
      and treating cocaine-induced lesions involving the craniovertebral junction are a
      challenge. 

PMID- 25955802
TI  - Predictors of delayed failure of structural kyphoplasty for pathological
      compression fractures in cancer patients.
AB  - OBJECT Pathological compression fractures in cancer patients cause significant
      pain and disability. Spinal metastases affect quality of life near the end of
      life and may require multiple procedures, including medical palliative care and
      open surgical decompression and fixation. An increasingly popular minimally
      invasive technique to treat metastatic instabilities is kyphoplasty. Even though
      it may alleviate pain due to pathological fractures, it may fail. However,
      delayed kyphoplasty failures with retropulsed cement and neural element
      compression have not been well reported. Such failures necessitate open surgical
      decompression and stabilization, and cement inserted during the kyphoplasty
      complicates salvage surgeries in patients with a disease-burdened spine. The
      authors sought to examine the incidence of delayed failure of structural
      kyphoplasty in a series of cement augmentations for pathological compression
      fractures. The goal was to identify risk predictors by analyzing patient and
      disease characteristics to reduce kyphoplasty failure and to prevent excessive
      surgical procedures at the end of life. METHODS The authors retrospectively
      reviewed the records of all patients with metastatic cancer from 2010 to 2013 who
      had undergone a procedure involving cement augmentation for a pathological
      compression fracture at their institution. The authors examined the
      characteristics of the patients, diseases, and radiographic fractures. RESULTS In
      total, 37 patients underwent cement augmentation in 75 spinal levels during 45
      surgeries. Four patients had delayed structural kyphoplasty failure necessitating
      surgical decompression and fusion. The mean time to kyphoplasty failure was 2.88
      +/- 1.24 months. The mean loss of vertebral body height was 16% in the patients
      in whom kyphoplasty failed and 32% in patients in whom kyphoplasty did not fail.
      No posterior intraoperative cement extravasation was observed in the patients in
      whom kyphoplasty had failed. The mean spinal instability neoplastic score was
      10.8 in the patients in whom kyphoplasty failed and 10.1 in those in whom
      kyphoplasty did not fail. Approximately 50% of the kyphoplasty failures occurred
      at junctional spinal levels. All the patients in whom kyphoplasty failed had
      fractures in 3 or more cortical walls before treatment, whereas 46% of patients
      in the nonfailure group had fractures with breaching of 3 or more walls.
      CONCLUSIONS Although rare, delayed failures of structural augmentation with
      cement during kyphoplasty do occur and can lead to additional surgeries. A
      possible predictive index may include wall integrity of the vertebral body,
      competency of the posterior tension band, and location of the kyphoplasty at a
      junctional spinal level. Additional studies are required to confirm these
      findings. 

PMID- 25955803
TI  - Can biomechanical studies make no distinction between different lumbar levels?

PMID- 25955801
TI  - Comparison of structural allograft and traditional autograft technique in
      occipitocervical fusion: radiological and clinical outcomes from a single
      institution.
AB  - OBJECT The authors' objectives were to compare the rate of fusion after
      occipitoatlantoaxial arthrodesis using structural allograft with the fusion rate
      from using autograft, to evaluate correction of radiographic parameters, and to
      describe symptom relief with each graft technique. METHODS The authors assessed
      radiological fusion at 6 and 12 months after surgery and obtained radiographic
      measurements of C1-2 and C2-7 lordotic angles, C2-7 sagittal vertical alignments,
      and posterior occipitocervical angles at preoperative, postoperative, and final
      follow-up examinations. Demographic data, intraoperative details, adverse events,
      and functional outcomes were collected from hospitalization records. Radiological
      fusion was defined as the presence of bone trabeculation and no movement between
      the graft and the occiput or C-2 on routine flexion-extension cervical
      radiographs. Radiographic measurements were obtained from lateral standing
      radiographs with patients in the neutral position. RESULTS At the University of
      Utah, 28 adult patients underwent occipitoatlantoaxial arthrodesis between 2003
      and 2010 using bicortical allograft, and 11 patients were treated using iliac
      crest autograft. Mean follow-up for all patients was 20 months (range 1-108
      months). Of the 27 patients with a minimum of 12 months of follow-up, 18 (95%) of
      19 in the allograft group and 8 (100%) of 8 in the autograft group demonstrated
      evidence of bony fusion shown by imaging. Patients in both groups demonstrated
      minimal deterioration of sagittal vertical alignment at final follow-up.
      Operative times were comparable, but patients undergoing occipitocervical fusion
      with autograft demonstrated greater blood loss (316 ml vs 195 ml). One (9%) of 11
      patients suffered a significant complication related to autograft harvesting.
      CONCLUSIONS The use of allograft in occipitocervical fusion allows a high rate of
      successful arthrodesis yet avoids the potentially significant morbidity and pain
      associated with autograft harvesting. The safety and effectiveness profile is
      comparable with previously published rates for posterior C1-2 fusion using
      allograft. 

PMID- 25955805
TI  - Construction of Identical [2 + 2] Schiff-Base Macrocyclic Ligands by Ln(III) and
      Zn(II) Template Ions Including Efficient Yb(III) Near-Infrared Sensitizers.
AB  - Identical 34-membered [2 + 2] pendent-armed Schiff-base macrocyclic ligands (H4La
      and H4Lb) can be constructed via the condensation reactions between rigid o
      phenylenediamine and extended dialdehydes (H2hpdd/H2pdd) in the presence of
      either Ln(III) or Zn(II) template with remarkable distinction on the ion radii
      and charge. X-ray single-crystal diffraction analyses reveal the formation of
      mononuclear Ln(III) complexes (1-4 and 7) and dinuclear Zn(II) complexes (5 and
      6). It is noted that Ln(III) macrocyclic complexes have eight-coordinate sandwich
      like mononuclear structures fully surrounded by flexible and large-sized
      macrocyclic ligands. Photophysical studies have demonstrated that both H4La and
      H4Lb can serve as effective sensitizers for the Yb(III) ion (2 and 7) exhibiting
      near-infrared emission at 974 nm with high quantum yields in solution (C2H5OH and
      CH3OH, ~1%). Moreover, the quantum yields of two Yb(III) complexes 2 and 7 could
      be increased ~15% in CH3OH under weak alkaline condition (pH = 8-9), while no
      significant changes are observed in C2H5OH by contrast. We think the unique
      sandwich-like macrocyclic structures of Yb(III) complexes 2 and 7 play important
      roles in simultaneously guaranteeing the effective match of the energy levels of
      Yb(III) centers as well as shielding from the solvent molecules and counterions. 

PMID- 25955804
TI  - Promotion of Cancer Cell Proliferation by Cleaved and Secreted Luminal Domains of
      ER Stress Transducer BBF2H7.
AB  - BBF2H7 is an endoplasmic reticulum (ER)-resident transmembrane basic leucine
      zipper (bZIP) transcription factor that is cleaved at the transmembrane domain by
      regulated intramembrane proteolysis in response to ER stress. The cleaved
      cytoplasmic N-terminus containing transcription activation and bZIP domains
      translocates into the nucleus to promote the expression of target genes. In
      chondrocytes, the cleaved luminal C-terminus is extracellularly secreted and
      facilitates proliferation of neighboring cells through activation of Hedgehog
      signaling. In the present study, we found that Bbf2h7 expression levels
      significantly increased by 1.070-2.567-fold in several tumor types including
      glioblastoma compared with those in respective normal tissues, using the ONCOMINE
      Cancer Profiling Database. In some Hedgehog ligand-dependent cancer cell lines
      including glioblastoma U251MG cells, the BBF2H7 C-terminus was secreted from
      cells into the culture media and promoted cancer cell proliferation through
      activation of Hedgehog signaling. Knockdown of Bbf2h7 expression suppressed the
      proliferation of U251MG cells by downregulating Hedgehog signaling. The impaired
      cell proliferation and Hedgehog signaling were recovered by addition of BBF2H7 C
      terminus to the culture medium of Bbf2h7-knockdown U251MG cells. These data
      suggest that the secreted luminal BBF2H7 C-terminus is involved in Hedgehog
      ligand-dependent cancer cell proliferation through activation of Hedgehog
      signaling. Thus, the BBF2H7 C-terminus may be a novel target for the development
      of anticancer drugs. 

PMID- 25955806
TI  - The long-term outcomes of radiosurgery for arteriovenous malformations in
      pediatric and adolescent populations.
AB  - OBJECT Although stereotactic radiosurgery (SRS) has been accepted as a
      therapeutic option for arteriovenous malformations (AVMs) in children and
      adolescents, substantial data are still lacking regarding the outcomes of SRS for
      AVMs in this age group, especially long-term complications. This study aimed to
      clarify the long-term outcomes of SRS for the treatment of AVM in pediatric
      patients aged <= 18 years. METHODS Outcomes of 116 patients who were aged 4-18
      years when they underwent SRS between 1990 and 2009 at the study institute were
      analyzed retrospectively. RESULTS The median follow-up period after SRS was 100
      months, with 6 patients followed up for more than 20 years. Actuarial
      obliteration rates at 3 and 5 years after SRS were 68% and 88%, respectively.
      Five hemorrhages occurred in 851 patient-years of follow-up. The annual bleeding
      rate after SRS before obliteration was calculated as 1.3%, which decreased to
      0.2% after obliteration. Shorter maximum nidus diameter (p = 0.02) and higher
      margin dose (p = 0.03) were associated with a higher obliteration rate. Ten
      patients experienced adverse events after SRS. Of them, 4 patients presented with
      delayed complications years after SRS (range 9-20 years after SRS). CONCLUSIONS
      SRS can reduce the risk of hemorrhage in pediatric and adolescent AVMs, with an
      acceptable risk of complications in the long term. However, adverse events such
      as expanding hematoma and radiation necrosis that can occur after substantial
      follow-up should be taken into account at the time that treatment decisions are
      made and informed consent is obtained. 

PMID- 25955807
TI  - Steal phenomenon in Sturge-Weber syndrome imitating an ictal
      electroencephalography change in the contralateral hemisphere: report of 2 cases.
AB  - Infants with Sturge-Weber syndrome (SWS) are considered for surgery if they
      develop seizures and the seizures prove medically refractory. The authors report
      on 2 infants (15 and 19 months old) with SWS who underwent scalp video
      electroencephalography (EEG) and subsequent functional hemispherotomy for
      intractable partial motor seizures due to extensive left hemispheric
      angiomatosis. They presented with similar interictal and ictal EEG findings.
      Ictal EEG showed abrupt high-amplitude delta slow waves, without evolution on the
      contralateral hemisphere before the build-up of ictal EEG changes on the lesional
      hemisphere. The patients became seizure free after hemispherotomy. The ictal
      contralateral slow waves were not a sign of an ictal hemisphere and may indicate
      prominent ischemic changes resulting from a steal phenomenon of hemispheric
      angiomatosis during seizure. 

PMID- 25955808
TI  - Radiological features of infantile glioblastoma and desmoplastic infantile
      tumors: British Columbia's Children's Hospital experience.
AB  - OBJECT Two of the more common infantile brain tumors, glioblastoma multiforme
      (GBM) and desmoplastic infantile tumors (DITs), can be difficult to distinguish
      on MRI. Both tumors occur in the supratentorial compartment and both have solid
      and cystic components. Differentiating between the 2 on MRI studies could assist
      the surgeon in discussions with family and child management. The authors report
      on their institutional experience with both tumors, focusing on radio-graphic
      features, especially the diffusion studies, which might be useful in
      distinguishing between infantile GBM and DIT. METHODS A retrospective review was
      undertaken of all infantile brain tumors treated at British Columbia's Children's
      Hospital between 1982 and 2012, and cases of GBM and DIT were recorded. Only
      cases that had imaging were included in the study. A literature review was
      completed to identify reported cases of infantile GBM and DIT. Only reports that
      described or included radiological studies (particularly MRI) of the tumors were
      included. Certain radiographic features of the tumors were reviewed, including
      location, size, consistency, pattern of enhancement, and features on MR diffusion
      studies. RESULTS Of 70 cases of infantile brain tumors, 2 GBM cases and 3 DIT
      cases (all 3 of which were desmoplastic infantile gangliogliomas [DIGs]) met the
      inclusion criteria. The radiological studies obtained in all 5 cases were
      reviewed by a neuroradiologist. All 5 patients had supratentorial tumors with
      cystic-solid consistency. Diffusion MRI studies showed restricted diffusion in
      the 2 GBM cases, but no evidence of restricted diffusion in the DIG tumors. The
      GBM tumors were heterogeneously enhancing, and the DIG tumors showed avid and
      homogeneous enhancement. The literature review revealed 29 cases of infantile GBM
      and 32 cases of DIG/DIT that met the inclusion criteria. The tumors were large in
      both groups. The tumors were cystic-solid in consistency in 10 of 30 (33%) of GBM
      cases and 28 of 32 (87.5%) of DIT cases. The contrast enhancement was
      heterogeneous in 9 of 30 (30%) GBM cases, and it was homogeneous and avid in 27
      of 32 (84%) of DIT cases. Diffusion studies were recorded in 2 published
      infantile GBM cases, and in both of them diffusion was restricted. The authors
      only found 1 report that discussed DIG tumor features on MR diffusion studies,
      but the interpretation was difficult and unclear. CONCLUSIONS Magnetic resonance
      imaging, especially diffusion-weighted imaging, may be a useful aid in
      distinguishing between infantile GBM and DIT tumors, with infantile GBM
      demonstrating restricted diffusion. 

PMID- 25955809
TI  - Incidence of seizures on continuous EEG monitoring following traumatic brain
      injury in children.
AB  - OBJECT Seizures may cause diagnostic confusion and be a source of metabolic
      stress after traumatic brain injury (TBI) in children. The incidence of
      electroencephalography (EEG)-confirmed seizures and of subclinical seizures in
      the pediatric population with TBI is not well known. METHODS A routine protocol
      for continuous EEG (cEEG) monitoring was initiated for all patients with moderate
      or severe TBI at a Level 1 pediatric trauma center. Over a 3.5-year period, all
      patients with TBI who underwent cEEG monitoring, both according to protocol and
      those with mild head injuries who underwent cEEG monitoring at the discretion of
      the treating team, were identified prospectively. Clinical data were collected
      and analyzed. RESULTS Over the study period, 594 children were admitted with TBI,
      and 144 of these children underwent cEEG monitoring. One hundred two (71%) of
      these 144 children had moderate or severe TBI. Abusive head trauma (AHT) was the
      most common mechanism of injury (65 patients, 45%) in children with cEEG
      monitoring. Seizures were identified on cEEG in 43 patients (30%). Forty (93%) of
      these 43 patients had subclinical seizures, including 17 (40%) with only
      subclinical seizures and 23 (53%) with both clinical and subclinical seizures.
      Fifty-three percent of patients with seizures experienced status epilepticus. Age
      less than 2.4 years and AHT mechanism were strongly correlated with presence of
      seizures (odds ratios 8.7 and 6.0, respectively). Those patients with only
      subclinical seizures had the same risk factors as the other groups. The presence
      of seizures did not correlate with discharge disposition but was correlated with
      longer hospital stay and intensive care unit stay. CONCLUSIONS Continuous EEG
      monitoring identifies a significant number of subclinical seizures acutely after
      TBI. Children younger than 2.4 years of age and victims of AHT are particularly
      vulnerable to subclinical seizures, and seizures in general. Continuous EEG
      monitoring allows for accurate diagnosis and timely treatment of posttraumatic
      seizures, and may mitigate secondary injury to the traumatized brain. 

PMID- 25955810
TI  - Differentiating infantile tumors with diffusion imaging.

PMID- 25955811
TI  - Pediatric hydrocephalus: systematic literature review and evidence-based
      guidelines. Part 6: Preoperative antibiotics for shunt surgery in children with
      hydrocephalus: a systematic review and meta-analysis.

PMID- 25955812
TI  - Regarding Pediatric Hydrocephalus Guidelines.

PMID- 25955813
TI  - Cell therapy in Duchenne muscular dystrophy treatment: clinical trials overview.
AB  - Duchenne muscular dystrophy (DMD), the most common and most severe form of all
      muscular dystrophies, leads to progressive muscle fiber necrosis, fibroblast
      proliferation, and growth of fibrous tissue and fat. The most common cause of
      death in DMD patients is cardiac and respiratory failure. Current pharmacological
      and other treatment methods do not lead to full recovery. For this reason, new
      alternatives for skeletal muscle regeneration are being investigated.
      Transplantation of myoblasts from healthy donors is one studied approach to
      muscle treatment in DMD patients. However, the results of intramuscular injection
      of in vitro cultured myoblasts are still not satisfactory. The use of autologous
      stem cells is also proposed. Despite many ongoing studies, this therapy is still
      in preliminary testing and requires more experiments. 

PMID- 25955814
TI  - Symptomatic versus Asymptomatic Intervertebral Disc Degeneration: Is Inflammation
      the Key?
AB  - Degenerated intervertebral discs (d-IVDs) contribute to low back pain (LBP) and
      are highly common. While some d-IVDs cause discogenic LBP, others are pain-free.
      Understanding the differences in pathophysiology between painful and pain-free
      intervertebral disc degeneration (IDD), especially the pathogenic signaling
      involved in the regulation of painful d-IVDs, is vital for achieving satisfactory
      effects in clinical treatment. In this review, we revisit recent findings on the
      detection of inflammatory factors in d-IVDs and summarize the differences between
      d-IVDs that are painful and those that are pain-free. We postulate that
      persistent inflammation and innervation are the key factors distinguishing those
      that are symptomatic and those that are not. This highlights the necessity to use
      painful, rather than pain-free, degenerated discs in the mechanistic study of
      disc degeneration and in the development of regenerative approaches, to avoid
      false positive/negative outcomes. Based on previous molecular d-IVD studies, we
      also postulate the signaling events from disc overload/ injury to discogenic
      pain. Although these proposed events are supported by experimental findings, many
      details about how they are interconnected are not addressed and therefore require
      experimental investigation. 

PMID- 25955815
TI  - Role of autophagy in photoreceptor cell survival and death.
AB  - Autophagy, a highly conserved self-degradation process that occurs under both
      physiological and pathological conditions, provides the raw material and energy
      for cell regeneration under normal circumstances. Dysregulated autophagy under
      diseased conditions may cause protein accumulation, organelle dysfunction, and
      even cell death. Recent studies have shown that autophagy regulates the
      structural integrity and physiological functions of retinal photoreceptor cells
      and contributes to the pathogenesis of retinopathies such as retinal detachment,
      age-related macular degeneration, retinitis pigmentosa, and Leber's congenital
      amaurosis. In this review, we discuss the role of autophagy in photoreceptor cell
      survival and death in retinal physiology and diseases, and suggest the
      possibility that autophagy-targeting therapy may be a new strategy for retinal
      diseases marked by photoreceptor cell death. 

PMID- 25955816
TI  - Management of osteoporosis in South Korea.
AB  - Epidemiologic studies have suggested that South Korea is a country with low risk
      rates of osteoporosis and osteoporotic fractures. Recently, the Korean Nationwide
      Databased Osteoporosis Study (KNOS) performed an overall analysis of osteoporosis
      using data from the Health Insurance Review and Assessments (HIRA) database. The
      Korean National Health Insurance Program covers almost 100% of the Korean
      population, and HIRA reviews all information on medication, operation, and
      discharge diagnoses according to ICD-10 codes. Therefore, all information about
      osteoporosis and osteoporotic fractures was obtained from this centralized
      database. This article reviews the KNOS's efforts to characterize the management
      of osteoporosis in South Korea. 

PMID- 25955817
TI  - NPR-A: A Therapeutic Target in Inflammation and Cancer.
AB  - Natriuretic peptide receptor A (NPR-A) is the receptor for atrial natriuretic
      peptide (ANP) and brain natriuretic peptide (BNP). NPR-A plays critical
      physiological and pathophysiological roles in several target cell and tissue
      system processes, such as cell growth, apoptosis, proliferation, and
      inflammation. Accumulating data demonstrate that NPR-A is involved in immune and
      inflammatory reactions and is a potential target in inflammation treatment. It is
      expressed in various cancer cells and is important for tumor growth. A recent
      study indicated that NPR-A signaling can regulate stem cell recruitment and
      angiogenesis. This signaling can serve as a model for studying the linkage
      between inflammation and tumorigenesis. In this review we highlight the
      mechanisms by which NPR-A affects signaling pathways involved in inflammation and
      cancer, and we discuss its potential as a novel target in inflammation, cancer,
      and cancer-related inflammation. 

PMID- 25955818
TI  - The Role Of Semaphorin 3A In The Skeletal System.
AB  - Semaphorin 3A (Sema3A), characterized by a conserved N-terminal "Sema" domain,
      was originally described as an axon guidance molecule. Recent research indicates
      that it performs a critical function in the skeletal system. This review
      highlights recent advances in understanding of the role of Sema3A in the skeletal
      system as a regulator of bone metabolism and as a potential drug target for bone
      disease therapy. We summarize Sema3A functions in osteoblastogenesis and
      osteoclastogenesis, as well as in innervation, and we discuss its multifunctional
      role in various bone diseases such as osteoporosis and low back pain. Despite
      limited research in this field, our aim is to promote further understanding of
      the function of Sema3A in the skeletal system. 

PMID- 25955819
TI  - mTOR, AMPK, and Sirt1: Key Players in Metabolic Stress Management.
AB  - Cells adapt their metabolism and activities in response to signals from their
      surroundings, and this ability is essential for their survival in the face of
      environmental changes. In mammalian tissues a deficit of these mechanisms is
      commonly associated with cellular aging and degenerative diseases related to
      aging, such as cardiovascular disease, cancer, immune system decline, and
      neurological pathologies. Several proteins have been identified as able to
      respond directly to energy, nutrient, and growth factor levels and stress stimuli
      in order to mediate adaptations in the cell. Many of these proteins are enzymes
      that positively or negatively modulate the autophagic process. This review
      focuses on biochemical mechanisms involving enzymes--specifically, mTOR, AMPK,
      and Sirt1--that are currently considered important for these adaptive responses,
      providing an overview of the interactions of the main players in this process.

PMID- 25955820
TI  - Emerging Roles of CCCH-Type Zinc Finger Proteins in Destabilizing mRNA Encoding
      Inflammatory Factors and Regulating Immune Responses.
AB  - Posttranscriptional gene regulation is a rapid and effective way to mediate the
      expression of inflammatory genes. CCCH-type zinc finger proteins are nucleotide
      binding molecules involved in RNA metabolism pathways such as RNA splicing,
      polyadenylation, and messenger RNA (mRNA) decay. Among these proteins,
      tristetraproline, Roquins, and Regnase-1/monocyte chemotactic protein-1-induced
      protein-1 have been recently reported to be responsible for mRNA instability.
      They bind to mRNAs harboring unique motifs and induce mRNA decay. In this review
      we summarize current progress regarding the specific characteristics of sequences
      and structures in the 3' untranslated regions of mRNAs that are recognized by
      tristetraproline, Roquins, and Regnase-1. The target mRNAs to be destabilized by
      those CCCH-type zinc finger proteins also are included. Notably, most target
      mRNAs encode cytokines and other inflammatory mediators, suggesting the immune
      regulation role of CCCH zinc finger proteins. Mice carrying a genetic null allele
      or modification of these genes display severe symptoms of autoimmune diseases.
      Taken together, data show that CCCH-type zinc finger proteins play a crucial role
      in regulating immune response by targeting multiple mRNAs, and including decay.
      Further understanding the functions of these proteins may provide new therapeutic
      targets for immune-related disorders in the future. 

PMID- 25955822
TI  - Responsiveness of selected outcome measures of participation restriction and
      quality of life in patients with multiple sclerosis.
AB  - PURPOSE: To evaluate the responsiveness of two outcome measures of participation
      restriction [as measured by the Community Integration Questionnaire (CIQ)] and
      quality of life [as measured by the Multiple Sclerosis Quality of Life (MSQOL)]
      following a physiotherapy intervention in patients with multiple sclerosis (MS).
      METHOD: A sample of 265 patients completed both instruments first at the time of
      initial visit and then after 4-6 weeks physiotherapy. In addition, patients were
      asked to complete the 7-point global rating scale as an external criterion of
      change at the post-intervention time. The responsiveness was evaluated using the
      receiver operating characteristics (ROC) method and the correlation analysis. Two
      useful statistics were area under the ROC curve (AUC) and the minimally
      clinically important difference (MCID). The AUC and correlation coefficient
      greater than 0.70 were considered as acceptable responsiveness. RESULTS: The CIQ
      achieved the acceptable responsiveness with an AUC of 0.81. However, the AUCs of
      0.61 and 0.66 were obtained for the MSQOL physical and mental, respectively.
      Moreover, good correlation coefficient was obtained for the CIQ (Gamma = 0.76)
      while fair correlations of 0.28 and 0.33 were obtained for the MSQOL physical and
      mental, respectively. The MCIDs were approximately 0.50, 1.5 and 2.5 points for
      the CIQ, MSQOL physical and mental, respectively. CONCLUSIONS: In contrast to the
      MSQOL, the CIQ was responsive outcome measure in detecting changes in
      participation restriction of patients with MS. Moreover, the MCID values obtained
      in this study will help the clinicians and researchers to determine if a patient
      with MS has experienced a true change following physiotherapy intervention.
      IMPLICATIONS FOR REHABILITATION: The results provide valuable information
      regarding to the ability of two outcome measures (i.e. the CIQ and MSQOL) to
      detect treatment effects in patients with MS. In contrast to the MSQOL, the CIQ
      is a responsive measure to changes in participation restriction due to
      physiotherapy. A patient with MS had to change at least 0.50 point on the CIQ,
      1.5 points on the MSQOL physical and 2.5 points on the MSQOL mental to be judged
      as having clinically changed.

PMID- 25955821
TI  - Replication of KCNJ11 (p.E23K) and ABCC8 (p.S1369A) Association in Russian
      Diabetes Mellitus 2 Type Cohort and Meta-Analysis.
AB  - The genes ABCC8 and KCNJ11 have received intense focus in type 2 diabetes
      mellitus (T2DM) research over the past two decades. It has been hypothesized that
      the p.E23K (KCNJ11) mutation in the 11p15.1 region may play an important role in
      the development of T2DM. In 2009, Hamming et al. found that the p.1369A (ABCC8)
      variant may be a causal factor in the disease; therefore, in this study we
      performed a meta-analysis to evaluate the association between these single
      nucleotide polymorphisms (SNPs), including our original data on the Siberian
      population (1384 T2DM and 414 controls). We found rs5219 and rs757110 were not
      associated with T2DM in this population, and that there was linkage
      disequilibrium in Siberians (D'=0.766, r(2)= 0.5633). In addition, the haplotype
      rs757110[T]-rs5219[C] (p.23K/p.S1369) was associated with T2DM (OR = 1.52, 95%
      CI: 1.04-2.24). We included 44 original studies published by June 2014 in a meta
      analysis of the p.E23K association with T2DM. The total OR was 1.14 (95% CI: 1.11
      1.17) for p.E23K for a total sample size of 137,298. For p.S1369A, a meta
      analysis was conducted on a total of 10 studies with a total sample size of
      14,136 and pooled OR of 1.14 [95% CI (1.08-1.19); p = 2 x 10-6]. Our calculations
      identified causal genetic variation within the ABCC8/KCNJ11 region for T2DM with
      an OR of approximately 1.15 in Caucasians and Asians. Moreover, the OR value was
      not dependent on the frequency of p.E23K or p.S1369A in the populations.

PMID- 25955823
TI  - Basic body awareness therapy or exercise therapy for the treatment of chronic
      whiplash associated disorders: a randomized comparative clinical trial.
AB  - PURPOSE: Chronic whiplash-associated disorders (WAD) incur both costs and
      suffering. Treatments that can relieve chronic WAD are therefore needed. Exercise
      therapy (ET) has been shown to provide pain relief. Another often used treatment
      for chronic pain in Scandinavia is basic body awareness therapy (BAT). We
      compared the effectiveness of 10 weeks of twice-weekly, 90-min sessions of either
      ET or BAT in a randomized comparative trial. METHOD: We recruited 113 patients
      suffering from chronic WAD grades I-III and several years' duration of symptoms
      in a primary health care setting. 57 were allocated to ET and 56 to BAT. Primary
      outcome measures were Neck Disability Index and SF-36 v.2. RESULTS: From baseline
      to post-treatment, the BAT group increased their physical functioning (median 5,
      IQR = 15) more than the ET group (median = 0, IQR = 15), p = 0.032, effect size 
      0.54. Three months after the end of treatment, the BAT group had less bodily pain
      (m = 17.5, 95% CI 6.9-17.6) than the ET group (m = 4.9, 95% CI -0.1 to 9.8), p =
      0.044, effect size -0.4. The BAT group had also increased their social
      functioning (m = 13.3, 95% CI 6.6-19.9) more than the ET group (m = 3.5, 95% CI 
      3 to 9.9), p = 0.037, effect size -0.41. No statistically significant differences
      between groups were found for the change of other outcomes. No serious adverse
      effects were found in either groups. CONCLUSIONS: The present trial indicates
      that BAT led to greater improvements than ET for the patients with chronic WAD.
      IMPLICATIONS FOR REHABILATION: Chronic whiplash-associated disorders are
      disabling and incur great costs to society often through inability to work.
      Exercise therapy (ET) may alleviate symptoms of chronic WAD. Basic body awareness
      therapy (BAT) is often a component of multimodal pain rehabilitation programs. In
      this randomized comparative trial, BAT increased physical functioning and led to
      greater pain reduction and social functioning 3 months after the end of
      treatment.

PMID- 25955824
TI  - gamma-Secretase inhibitor inhibits bladder cancer cell drug resistance and
      invasion by reducing epithelial-mesenchymal transition.
AB  - A previous study by our group demonstrated that the expression levels of Notch 1
      and Jagged 1 in bladder cancer cells was significantly lower compared with those
      in normal bladder mucosa, while the expression levels of Notch 1 and Jagged 1 in
      invasive bladder cancer were higher compared with those in superficial bladder
      cancer. The present study investigated the effect of the Notch signaling pathway
      on the drug resistance and invasiveness of bladder cancer cells. It was
      demonstrated that complete inhibition of the Notch signaling pathway induced
      significant morphological changes and inhibited cell proliferation and migration
      (P<0.05). Reverse transcription quantitative polymerase chain reaction and
      western blot analyses revealed that the mRNA and protein expression levels of E
      cadherin were upregulated (P<0.05) and the mRNA and protein expression levels of
      N-cadherin, vimentin and alpha-smooth muscle actin were downregulated (P<0.05).
      The present study concluded that complete inhibition of the Notch signaling
      pathway inhibited cell proliferation and invasion, and reduced drug resistance in
      bladder cancer cells, a phenomenon which may be associated with the inhibition of
      the epithelial-mesenchymal transition.

PMID- 25955825
TI  - Postfunctionalization of BN-embedded polycyclic aromatic compounds for fine
      tuning of their molecular properties.
AB  - New BN-embedded, thiophene-fused, polycyclic aromatic compounds with planar
      geometry were designed and synthesized. The molecules showed excellent stability
      and chemical robustness. Postfunctionalization on this skeleton was demonstrated
      with a series of electrophilic bromination, palladium-catalyzed cross-coupling,
      and Knoevenagel condensation reactions. The pi skeleton remained intact during
      these late-stage transformations. The optical and electronic properties have been
      well tuned through incorporation of electron-rich and -deficient groups on the
      backbone. This work shows the great advantage of the postfunctionalization
      strategy on BN-containing polycyclic aromatic compounds for fast diversification
      and materials screening. 

PMID- 25955826
TI  - Ionic Selectivity and Permeation Properties of Human PIEZO1 Channels.
AB  - Members of the eukaryotic PIEZO family (the human orthologs are noted hPIEZO1 and
      hPIEZO2) form cation-selective mechanically-gated channels. We characterized the
      selectivity of human PIEZO1 (hPIEZO1) for alkali ions: K+, Na+, Cs+ and Li+;
      organic cations: TMA and TEA, and divalents: Ba2+, Ca2+, Mg2+ and Mn2+. All
      monovalent ions permeated the channel. At a membrane potential of -100 mV, Cs+,
      Na+ and K+ had chord conductances in the range of 35-55 pS with the exception of
      Li+, which had a significantly lower conductance of ~ 23 pS. The divalents
      decreased the single-channel permeability of K+, presumably because the divalents
      permeated slowly and occupied the open channel for a significant fraction of the
      time. In cell-attached mode, 90 mM extracellular divalents had a conductance for
      inward currents carried by the divalents of: 25 pS for Ba2+ and 15 pS for Ca2+ at
      -80 mV and 10 pS for Mg2+ at -50 mV. The organic cations, TMA and TEA, permeated
      slowly and attenuated K+ currents much like the divalents. As expected, the
      channel K+ conductance increased with K+ concentration saturating at ~ 45 pS and
      the KD of K+ for the channel was 32 mM. Pure divalent ion currents were of lower
      amplitude than those with alkali ions and the channel opening rate was lower in
      the presence of divalents than in the presence of monovalents. Exposing cells to
      the actin disrupting reagent cytochalasin D increased the frequency of openings
      in cell-attached patches probably by reducing mechanoprotection. 

PMID- 25955827
TI  - The Results of Toric Intraocular Lens Implantation in Patients With Cataract and
      High Astigmatism After Penetrating Keratoplasty.
AB  - OBJECTIVES: To evaluate the results of toric intraocular lens (IOL) implantation
      in patients with cataract and postpenetrating keratoplasty astigmatism. METHODS:
      Seven eyes of 7 patients with cataract and more than 3.5 diopters (D) astigmatism
      following penetrating keratoplasty were included in this retrospective case
      series study. All of the eyes underwent phacoemulsification and Acrysof toric IOL
      (t5-t9) implantation at least 6 months later than the complete suture removal.
      Corrected visual acuity (CVA), manifest astigmatism, the keratometry
      measurements, and complications were assessed. RESULTS: The mean preoperative CVA
      significantly increased (0.7+/-0.3 [range: 0.3-1.3] logMAR to 0.1+/-0.04 [range:
      0.05-0.15] logMAR; P<0.05) at mean 8.71+/-4.11 months after the surgery. The mean
      preoperative corneal astigmatism and the average manifest refractive astigmatism
      at the last visit were 5.4+/-0.9 D (range: 4.25-7 D) and 1.6+/-0.6 D (range: 0.5
      2.5 D), respectively. The mean attempted cylinder correction at spectacle plane
      was 4.3+/-0.9 D (range: 2.4-4.7 D) whereas the mean cylinder correction was 4.6+/
      0.5 D (range: 3.9-5.9 D), showing a slightly tendency for overcorrection. All
      eyes (100%) were within 1 D of predicted residual astigmatism. No complication
      occurred during the follow-up. CONCLUSION: Toric IOL implantation seems to be an
      effective, predictable, and safe procedure in patients with cataract formation
      and high astigmatism after penetrating keratoplasty.

PMID- 25955828
TI  - The NLRP3 Inflammasome Is a Pathogen Sensor for Invasive Entamoeba histolytica
      via Activation of alpha5beta1 Integrin at the Macrophage-Amebae Intercellular
      Junction.
AB  - Entamoeba histolytica (Eh) is an extracellular protozoan parasite of humans that
      invades the colon to cause life-threatening intestinal and extra-intestinal
      amebiasis. Colonized Eh is asymptomatic, however, when trophozoites adhere to
      host cells there is a considerable inflammatory response that is critical in the
      pathogenesis of amebiasis. The host and/or parasite factors that trigger the
      inflammatory response to invading Eh are not well understood. We recently
      identified that Eh adherence to macrophages induces inflammasome activation and
      in the present study we sought to determine the molecular events upon contact
      that coordinates this response. Here we report that Eh contact-dependent
      activation of alpha5beta1 integrin is critical for activation of the NLRP3
      inflammasome. Eh-macrophage contact triggered recruitment of alpha5beta1 integrin
      and NLRP3 into the intercellular junction, where alpha5beta1 integrin underwent
      activation by an integrin-binding cysteine protease on the parasite surface,
      termed EhCP5. As a result of its activation, alpha5beta1 integrin induced ATP
      release into the extracellular space through opening of pannexin-1 channels that
      signalled through P2X7 receptors to deliver a critical co-stimulatory signal that
      activated the NLRP3 inflammasome. Both the cysteine protease activity and
      integrin-binding domain of EhCP5 were required to trigger alpha5beta1 integrin
      that led to ATP release and NLRP3 inflammasome activation. These findings reveal
      engagement of alpha5beta1 integrin across the parasite-host junction is a key
      regulatory step that initiates robust inflammatory responses to Eh. We propose
      that alpha5beta1 integrin distinguishes Eh direct contact and functions with
      NLRP3 as pathogenicity sensor for invasive Eh infection. 

PMID- 25955829
TI  - Function and mechanism of F-box proteins in gastric cancer (Review).
AB  - Gastric cancer (GC) is one of the commonest cancers with high mortality. Despite
      improvement in early detection and treatments, the outcome of advanced GC remains
      unsatisfactory due to the poor understanding of the intricate pathogenesis of GC.
      GC is a multifactorial and multistep disease which involves activation of
      oncogenes and inactivation of tumor suppressor genes. Ubiquitin proteasome system
      (UPS) catalyzing many critical protein substrates is involved in initiation and
      development of cancer. F-box proteins (FBPs) are the main functional components
      of UPS. Accumulated evidence strongly suggests that abnormal regulations of FBPs
      contribute to uncontrolled proliferation, genomic instability and cancer. In this
      review, we discuss how the dysregulated FBPs promote the occurrence and
      development of GC.

PMID- 25955830
TI  - Correction: Genetic Diversity of the Coat Protein of Olive Mild Mosaic Virus
      (OMMV) and Tobacco Necrosis Virus D (TNV-D) Isolates and Its Structural
      Implications.

PMID- 25955831
TI  - Research on laser marking speed optimization by using genetic algorithm.
AB  - Laser Marking Machine is the most common coding equipment on product packaging
      lines. However, the speed of laser marking has become a bottleneck of production.
      In order to remove this bottleneck, a new method based on a genetic algorithm is
      designed. On the basis of this algorithm, a controller was designed and
      simulations and experiments were performed. The results show that using this
      algorithm could effectively improve laser marking efficiency by 25%. 

PMID- 25955832
TI  - Immediate and delayed cochlear neuropathy after noise exposure in pubescent mice.
AB  - Moderate acoustic overexposure in adult rodents is known to cause acute loss of
      synapses on sensory inner hair cells (IHCs) and delayed degeneration of the
      auditory nerve, despite the completely reversible temporary threshold shift (TTS)
      and morphologically intact hair cells. Our objective was to determine whether a
      cochlear synaptopathy followed by neuropathy occurs after noise exposure in
      pubescence, and to define neuropathic versus non-neuropathic noise levels for
      pubescent mice. While exposing 6 week old CBA/CaJ mice to 8-16 kHz bandpass noise
      for 2 hrs, we defined 97 dB sound pressure level (SPL) as the threshold for this
      particular type of neuropathic exposure associated with TTS, and 94 dB SPL as the
      highest non-neuropathic noise level associated with TTS. Exposure to 100 dB SPL
      caused permanent threshold shift although exposure of 16 week old mice to the
      same noise is reported to cause only TTS. Amplitude of wave I of the auditory
      brainstem response, which reflects the summed activity of the cochlear nerve, was
      complemented by synaptic ribbon counts in IHCs using confocal microscopy, and by
      stereological counts of peripheral axons and cell bodies of the cochlear nerve
      from 24 hours to 16 months post exposure. Mice exposed to neuropathic noise
      demonstrated immediate cochlear synaptopathy by 24 hours post exposure, and
      delayed neurodegeneration characterized by axonal retraction at 8 months, and
      spiral ganglion cell loss at 8-16 months post exposure. Although the damage was
      initially limited to the cochlear base, it progressed to also involve the
      cochlear apex by 8 months post exposure. Our data demonstrate a fine line between
      neuropathic and non-neuropathic noise levels associated with TTS in the pubescent
      cochlea. 

PMID- 25955833
TI  - Failure of a Single Varicella Vaccination to Protect Children With Cancer From
      Life-Threatening Breakthrough Varicella.
AB  - We report 2 children with life-threatening breakthrough varicella. Both had
      received 1 varicella vaccination before onset of cancer. Despite treatment with
      intravenous acyclovir, 1 child died of disseminated varicella. Because similar
      fatal cases have been reported, high-risk immunocompromised children with 1
      varicella vaccination may warrant the same varicella prophylaxis as
      immunocompromised children who have never been vaccinated. 

PMID- 25955834
TI  - Comparative Effectiveness of Beta-lactam Versus Macrolide Monotherapy in Children
      with Pneumonia Diagnosed in the Outpatient Setting.
AB  - BACKGROUND: Most children diagnosed with community-acquired pneumonia (CAP) are
      treated in the outpatient setting. The objective of this study was to determine
      the comparative clinical effectiveness of beta-lactam monotherapy and macrolide
      monotherapy in this population. STUDY DESIGN: Children, 1-18 years old, with a
      clinical diagnosis of CAP at an outpatient practice affiliated (n = 71) with
      Geisinger Health System during January 1, 2008 to January 31, 2010 were eligible.
      The primary exposure was receipt of beta-lactam or macrolide monotherapy. The
      primary outcome was treatment failure defined as change in antibiotic
      prescription within 14 days of the initial pneumonia diagnosis. Propensity scores
      were used to determine the likelihood of receiving macrolide monotherapy.
      Treatment groups were matched 1:1, based on propensity score, age group and
      asthma status. Multivariable conditional logistic regression models estimated the
      association between macrolide monotherapy and treatment failures. RESULTS: Of
      1999 children with CAP, 1164 were matched. In the matched cohorts, 24% of
      children had asthma. Patients who received macrolide monotherapy had no
      statistical difference in treatment failure regardless of age when compared with
      patients who received beta-lactam monotherapy. CONCLUSION: Our findings suggest
      that children diagnosed with CAP in the outpatient setting and treated with beta
      lactam or macrolide monotherapy have the same likelihood to fail treatment
      regardless of age.

PMID- 25955836
TI  - Temporal Trends in Patient Characteristics and Outcomes Among Children Enrolled
      in Mozambique's National Antiretroviral Therapy Program.
AB  - BACKGROUND: During 2004-2009, >12,000 children (<15 years old) initiated
      antiretroviral therapy (ART) in Mozambique. Nationally representative outcomes
      and temporal trends in outcomes were investigated. METHODS: Rates of death, loss
      to follow-up (LTFU) and attrition (death or LTFU) were evaluated in a nationally
      representative sample of 1054 children, who initiated ART during 2004-2009 at 25
      facilities randomly selected using probability-proportional-to-size sampling.
      RESULTS: At ART initiation during 2004-2009, 50% were male; median age was 3.3
      years; median CD4% was 13%; median CD4 count was 375 cells/MUL; median weight-for
      age Z score was -2.1. During 2004-2009, median time from HIV diagnosis to care
      initiation declined from 33 to 0 days (P = 0.001); median time from care to ART
      declined from 93 to 62 days (P = 0.004); the percentage aged <2 at ART initiation
      increased from 16% to 48% (P = 0.021); the percentage of patients with prior
      tuberculosis declined from 50% to 10% (P = 0.009); and the percentage with prior
      lymphocytic interstitial pneumonia declined from 16% to 1% (P < 0.001). Over 2652
      person-years of ART, 183 children became LTFU and 26 died. Twelve-month attrition
      was 11% overall but increased from 3% to 22% during 2004-2009, mainly because of
      increases in 12-month LTFU (from 3% to 18%). CONCLUSION: Declines in the
      prevalence of markers of advanced HIV disease at ART initiation probably reflect
      increasing ART access. However, 12-month LTFU increased during program expansion,
      and this negated any program improvements in outcomes that might have resulted
      from earlier ART initiation.

PMID- 25955837
TI  - Monitoring the Impact of Vaccination on Pertussis in Infants Using an Active
      Hospital-based Pediatric Surveillance Network: Results from 17 Years' Experience,
      1996-2012, France.
AB  - BACKGROUND: Despite a high vaccine coverage in France in children, a resurgence
      of pertussis in infants too young to be protected by vaccination was observed in
      the 1990 s, leading to additional vaccination strategies in older age groups.
      This article describes the epidemiologic trends and characteristics of cases
      among infants 0-5 months of age during 17 years of pertussis surveillance through
      Renacoq. METHODS: Renacoq is a sentinel hospital-based voluntary surveillance
      network covering about 30% of hospitalized pertussis pediatric cases. It includes
      microbiologists and pediatricians from 42 large hospitals. RESULTS: Since March
      1996, the network has described 2227 cases of pertussis in infants aged 0-5
      months of whom 67.7% were infants 0-2 months of age. Four epidemic peaks
      occurred. The estimated national average incidence rate for the children aged 0-2
      months decreased significantly between 1996-1998 and 2008-2012 from 264 to 179
      per 100,000. Globally, 18.4% of cases were admitted to an intensive care unit,
      and the average case fatality ratio was 1%. Two-thirds (67.1%) of infants aged 3
      5 months were not correctly vaccinated according to age. Parents accounted for 41
      57% of the infections and siblings for 17-24%. CONCLUSIONS: Renacoq data
      confirmed the risk for young children and the need of timely pertussis
      vaccination. Parents and sibling remain the main source of infection, despite
      addition of boosters targeting sibling and parents. Improving vaccination
      coverage in adults in contact with young infants is needed. The continuation of
      Renacoq surveillance will allow monitoring the impact of additional vaccination
      strategies.

PMID- 25955838
TI  - Lack of K-Dependent Oxidative Stress in Cotton Roots Following Coronatine-Induced
      ROS Accumulation.
AB  - Coronatine [COR] is a novel type of plant growth regulator with similarities in
      structure and property to jasmonate. The objective of this study was to examine
      the relationship between increased root vitality induced by 10 nM COR and
      reactive oxygen species scavenging under potassium (K)-replete (2.5 mM) and K
      deficient (0.05 mM) conditions in hydroponic cultured cotton seedlings. K-replete
      and K-deficient conditions increased root vitality by 2.7- and 3.5-fold,
      respectively. COR treatment significantly decreased lipid peroxidation in cotton
      seedlings determined by reduction in MDA levels. These results suggest that COR
      improves the functioning of both enzymatic and non-enzymatic antioxidant systems.
      Under K-replete and K-deficient conditions, COR significantly increased the
      activities of antioxidant enzymes SOD (only for K-repletion), CAT, GPX, and APX
      comparing; COR also significantly increased DPPH-radical scavenging activity.
      However, COR led to 1.6- and 1.7-fold increases in superoxide anion (O2*-)
      concentrations, and 5.7- and 2.1-fold increases in hydrogen peroxide (H2O2)
      levels, respectively. Additionally, COR intensified the DAB staining of H2O2 and
      the NBT staining of O2*-. Therefore, our results reveal that COR-induced ROS
      accumulation stimulates the activities of most antioxidant enzymes but does not
      induce oxidative stress in cotton roots.

PMID- 25955835
TI  - Effect of Age at Antiretroviral Therapy Initiation on Catch-up Growth Within the
      First 24 Months Among HIV-infected Children in the IeDEA West African Pediatric
      Cohort.
AB  - BACKGROUND: We described malnutrition and the effect of age at antiretroviral
      therapy (ART) initiation on catch-up growth over 24 months among HIV-infected
      children enrolled in the International epidemiologic Databases to Evaluate Aids
      West African paediatric cohort. METHODS: Malnutrition was defined at ART
      initiation (baseline) by a Z score <-2 standard deviations, according to 3
      anthropometric indicators: weight-for-age (WAZ) for underweight, height-for-age
      (HAZ) for stunting and weight-for-height/BMI-for-age (WHZ/BAZ) for wasting.
      Kaplan-Meier estimates for catch-up growth (Z score >=-2 standard deviations) on
      ART, adjusted for gender, immunodeficiency and malnutrition at ART initiation,
      ART regimen, time period and country, were compared by age at ART initiation. Cox
      proportional hazards regression models determined predictors of catch-up growth
      on ART over 24 months. RESULTS: Between 2001 and 2012, 2004 HIV-infected children
      <10 years of age were included. At ART initiation, 51% were underweight, 48% were
      stunted and 33% were wasted. The 24-month adjusted estimates for catch-up growth
      were 69% [95% confidence interval (CI): 57-80], 61% (95% CI: 47-70) and 90% (95%
      CI: 76-95) for WAZ, HAZ and WHZ/BAZ, respectively. Adjusted catch-up growth was
      more likely for children <5 years of age at ART initiation compared with children
      >=5 years for WAZ, HAZ (P < 0.001) and WHZ/BAZ (P = 0.026). CONCLUSIONS:
      Malnutrition among these children is an additional burden that has to be urgently
      managed. Despite a significant growth improvement after 24 months on ART,
      especially in children <5 years, a substantial proportion of children still never
      achieved catch-up growth. Nutritional care should be part of the global
      healthcare of HIV-infected children in sub-Saharan Africa.

PMID- 25955840
TI  - Barley Stripe Mosaic Virus (BSMV) Induced MicroRNA Silencing in Common Wheat
      (Triticum aestivum L.).
AB  - MicroRNAs (miRNAs) play important roles in growth, development, and response to
      environmental changes in plants. Based on the whole-genome shotgun sequencing
      strategy, more and more wheat miRNAs have been annotated. Now, there is a need
      for an effective technology to analyse endogenous miRNAs function in wheat. We
      report here that the modified barley stripe mosaic virus (BSMV)-induced miRNAs
      silencing system can be utilized to silence miRNAs in wheat. BSMV-based miRNA
      silencing system is performed through BSMV-based expression of miRNA target
      mimics to suppress miR159a and miR3134a. The relative expression levels of mature
      miR159a and miR3134a decrease with increasing transcript levels of their target
      genes in wheat plants. In summary, the developed approach is effective in
      silencing endogenous miRNAs, thereby providing a powerful tool for biological
      function analyses of miRNA molecules in common wheat. 

PMID- 25955839
TI  - Differential Gene Expression Profiling of Dystrophic Dog Muscle after MuStem Cell
      Transplantation.
AB  - BACKGROUND: Several adult stem cell populations exhibit myogenic regenerative
      potential, thus representing attractive candidates for therapeutic approaches of
      neuromuscular diseases such as Duchenne Muscular Dystrophy (DMD). We have
      recently shown that systemic delivery of MuStem cells, skeletal muscle-resident
      stem cells isolated in healthy dog, generates the remodelling of muscle tissue
      and gives rise to striking clinical benefits in Golden Retriever Muscular
      Dystrophy (GRMD) dog. This global effect, which is observed in the clinically
      relevant DMD animal model, leads us to question here the molecular pathways that
      are impacted by MuStem cell transplantation. To address this issue, we compare
      the global gene expression profile between healthy, GRMD and MuStem cell treated
      GRMD dog muscle, four months after allogenic MuStem cell transplantation.
      RESULTS: In the dystrophic context of the GRMD dog, disease-related deregulation
      is observed in the case of 282 genes related to various processes such as
      inflammatory response, regeneration, calcium ion binding, extracellular matrix
      organization, metabolism and apoptosis regulation. Importantly, we reveal the
      impact of MuStem cell transplantation on several molecular and cellular pathways
      based on a selection of 31 genes displaying signals specifically modulated by the
      treatment. Concomitant with a diffuse dystrophin expression, a histological
      remodelling and a stabilization of GRMD dog clinical status, we show that cell
      delivery is associated with an up-regulation of genes reflecting a sustained
      enhancement of muscle regeneration. We also identify a decreased mRNA expression
      of a set of genes having metabolic functions associated with lipid homeostasis
      and energy. Interestingly, ubiquitin-mediated protein degradation is highly
      enhanced in GRMD dog muscle after systemic delivery of MuStem cells. CONCLUSIONS:
      Overall, our results provide the first high-throughput characterization of GRMD
      dog muscle and throw new light on the complex molecular/cellular effects
      associated with muscle repair and the clinical efficacy of MuStem cell-based
      therapy.

PMID- 25955841
TI  - Asymmetric lipid membranes: towards more realistic model systems.
AB  - Despite the ubiquity of transbilayer asymmetry in natural cell membranes, the
      vast majority of existing research has utilized chemically well-defined symmetric
      liposomes, where the inner and outer bilayer leaflets have the same composition.
      Here, we review various aspects of asymmetry in nature and in model systems in
      anticipation for the next phase of model membrane studies. 

PMID- 25955842
TI  - In vivo Quantification of the Effects of Radiation and Presence of Hair Follicle
      Pores on the Proliferation of Fibroblasts in an Acellular Human Dermis in a
      Dorsal Skinfold Chamber: Relevance for Tissue Reconstruction following
      Neoadjuvant Therapy.
AB  - INTRODUCTION: In neoadjuvant therapy, irradiation has a deleterious effect on
      neoangiogenesis. The aim of this study was to examine the post-implantation
      effects of neoadjuvant irradiation on the survival and proliferation of
      autologous cells seeded onto an acellular human dermis (hAD; Epiflex).
      Additionally, we examined the influence of dermal hair follicle pores on
      viability and proliferation. We used dorsal skinfold chambers implanted in rats
      and in-situ microscopy to quantify cell numbers over 9 days. METHODS: 24 rats
      received a skinfold chamber and were divided into 2 main groups; irradiated and
      unirradiated. In the irradiated groups 20Gy were applied epicutaneously at the
      dorsum. Epiflex pieces were cut to size 5x5mm such that each piece had either one
      or more visible hair follicle pores, or no such visible pores. Fibroblasts were
      transduced lentiviral with a fluorescent protein for cell tracking. Matrices were
      seeded statically with 2.5x104 fluorescent fibroblasts and implanted into the
      chambers. In each of the two main groups, half of the rats received Epiflex with
      hair follicle pores and half received Epiflex without pores. Scaffolds were
      examined in-situ at 0, 3, 6 and 9 days after transplantation. Visible cells on
      the surface were quantified using ImageJ. RESULTS: In all groups cell numbers
      were decreased on day 3. A treatment-dependent increase in cell numbers was
      observed at subsequent time points. Irradiation had an adverse effect on cell
      survival and proliferation. The number of cells detected in both irradiated and
      non-irradiated subjects was increased in those subjects that received transplants
      with hair follicle pores. DISCUSSION: This in-vivo study confirms that radiation
      negatively affects the survival and proliferation of fibroblasts seeded onto a
      human dermis transplant. The presence of hair follicle pores in the dermis
      transplants is shown to have a positive effect on cell survival and proliferation
      even in irradiated subjects.

PMID- 25955843
TI  - Metformin Causes G1-Phase Arrest via Down-Regulation of MiR-221 and Enhances
      TRAIL Sensitivity through DR5 Up-Regulation in Pancreatic Cancer Cells.
AB  - Although many chemotherapeutic strategies against cancer have been developed,
      pancreatic cancer is one of the most aggressive and intractable types of
      malignancies. Therefore, new strategies and anti-cancer agents are necessary to
      treat this disease. Metformin is a widely used drug for type-2 diabetes, and is
      also known as a promising candidate anti-cancer agent from recent studies in
      vitro and in vivo. However, the mechanisms of metformin's anti-cancer effects
      have not been elucidated. We demonstrated that metformin suppressed the
      expression of miR-221, one of the most well-known oncogenic microRNAs, in human
      pancreatic cancer PANC-1 cells. Moreover, we showed that the down-regulation of
      miR-221 by metformin caused G1-phase arrest via the up-regulation of p27, one of
      the direct targets of miR-221. Tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL) is also a promising agent for cancer treatment. While recent
      studies showed that treatment with only TRAIL was not effective against
      pancreatic cancer cells, the present data showed that metformin sensitized p53
      mutated pancreatic cancer cells to TRAIL. Metformin induced the expressions of
      death receptor 5 (DR5), a receptor for TRAIL, and Bim with a pro-apoptotic
      function in the downstream of TRAIL-DR5 pathway. We suggest that the up
      regulation of these proteins may contribute to sensitization of TRAIL-induced
      apoptosis. The combination therapy of metformin and TRAIL could therefore be
      effective in the treatment of pancreatic cancer. 

PMID- 25955844
TI  - Interrogating the Venom of the Viperid Snake Sistrurus catenatus edwardsii by a
      Combined Approach of Electrospray and MALDI Mass Spectrometry.
AB  - The complete sequence characterization of snake venom proteins by mass
      spectrometry is rather challenging due to the presence of multiple isoforms from
      different protein families. In the present study, we investigated the tryptic
      digest of the venom of the viperid snake Sistrurus catenatus edwardsii by a
      combined approach of liquid chromatography coupled to either electrospray
      (online) or MALDI (offline) mass spectrometry. These different ionization
      techniques proved to be complementary allowing the identification a great variety
      of isoforms of diverse snake venom protein families, as evidenced by the
      detection of the corresponding unique peptides. For example, ten out of eleven
      predicted isoforms of serine proteinases of the venom of S. c. edwardsii were
      distinguished using this approach. Moreover, snake venom protein families not
      encountered in a previous transcriptome study of the venom gland of this snake
      were identified. In essence, our results support the notion that complementary
      ionization techniques of mass spectrometry allow for the detection of even subtle
      sequence differences of snake venom proteins, which is fundamental for future
      structure-function relationship and possible drug design studies. 

PMID- 25955845
TI  - Gut microbial dysbiosis may predict diarrhea and fatigue in patients undergoing
      pelvic cancer radiotherapy: a pilot study.
AB  - Fatigue and diarrhea are the most frequent adverse effects of pelvic
      radiotherapy, while their etiologies are largely unknown. The aim of this study
      is to investigate the correlations between fatigue, diarrhea, and alterations in
      gut microbiota induced by pelvic radiotherapy. During the 5-week treatment of
      pelvic radiotherapy in 11 cancer patients, the general fatigue score
      significantly increased and was more prominent in the patients with diarrhea. The
      fatigue score was closely correlated with the decrease of serum citrulline (an
      indicator of the functional enterocyte mass) and the increases of systemic
      inflammatory proteins, including haptoglobin, orosomuoid, alpha1-antitrypsin and
      TNF-alpha. Serum level of lipopolysaccharide (LPS) was also elevated, especially
      in the patients with diarrhea indicating epithelial barrier breach and
      endotoxemia. Pyrosequencing analysis of 16S rRNA gene revealed that microbial
      diversity, richness, and the Firmicutes/Bacteroidetes ratio were significantly
      altered prior to radiotherapy in patients who later developed diarrhea. Pelvic
      radiotherapy induced further changes in fecal microbial ecology, some of which
      were specific to the patients with or without diarrhea. Our results indicate that
      gut microbial dysbiosis prior to radiation therapy may be exploited to predict
      development of diarrhea and to guide preventive treatment options. Radiation
      induced dysbiosis may contribute to pelvic radiation disease, including
      mucositis, diarrhea, systemic inflammatory response, and pelvic radiotherapy
      associated fatigue in cancer patients. 

PMID- 25955846
TI  - Auditory mismatch negativity and repetition suppression deficits in schizophrenia
      explained by irregular computation of prediction error.
AB  - BACKGROUND: The predictive coding model is rapidly gaining attention in
      schizophrenia research. It posits the neuronal computation of residual variance
      ('prediction error') between sensory information and top-down expectation through
      multiple hierarchical levels. Event-related potentials (ERP) reflect cortical
      processing stages that are increasingly interpreted in the light of the
      predictive coding hypothesis. Both mismatch negativity (MMN) and repetition
      suppression (RS) measures are considered a prediction error correlates based on
      error detection and error minimization, respectively. METHODS: Twenty-five
      schizophrenia patients and 25 healthy controls completed auditory tasks designed
      to elicit MMN and RS responses that were investigated using repeated measures
      models and strong spatio-temporal a priori hypothesis based on previous research.
      Separate correlations were performed for controls and schizophrenia patients,
      using age and clinical variables as covariates. RESULTS: MMN and RS deficits were
      largely replicated in our sample of schizophrenia patients. Moreover, MMN and RS
      measures were strongly correlated in healthy controls, while no correlation was
      found in schizophrenia patients. Single-trial analyses indicated significantly
      lower signal-to-noise ratio during prediction error computation in schizophrenia.
      CONCLUSIONS: This study provides evidence that auditory ERP components relevant
      for schizophrenia research can be reconciled in the light of the predictive
      coding framework. The lack of any correlation between the investigated measures
      in schizophrenia patients suggests a disruption of predictive coding mechanisms
      in general. More specifically, these results suggest that schizophrenia is
      associated with an irregular computation of residual variance between sensory
      input and top-down models, i.e. prediction error.

PMID- 25955847
TI  - Computational Ranking of Yerba Mate Small Molecules Based on Their Predicted
      Contribution to Antibacterial Activity against Methicillin-Resistant
      Staphylococcus aureus.
AB  - The aqueous extract of yerba mate, a South American tea beverage made from Ilex
      paraguariensis leaves, has demonstrated bactericidal and inhibitory activity
      against bacterial pathogens, including methicillin-resistant Staphylococcus
      aureus (MRSA). The gas chromatography-mass spectrometry (GC-MS) analysis of two
      unique fractions of yerba mate aqueous extract revealed 8 identifiable small
      molecules in those fractions with antimicrobial activity. For a more
      comprehensive analysis, a data analysis pipeline was assembled to prioritize
      compounds for antimicrobial testing against both MRSA and methicillin-sensitive
      S. aureus using forty-two unique fractions of the tea extract that were generated
      in duplicate, assayed for activity, and analyzed with GC-MS. As validation of our
      automated analysis, we checked our predicted active compounds for activity in
      literature references and used authentic standards to test for antimicrobial
      activity. 3,4-dihydroxybenzaldehyde showed the most antibacterial activity
      against MRSA at low concentrations in our bioassays. In addition, quinic acid and
      quercetin were identified using random forests analysis and 5-hydroxy pipecolic
      acid was identified using linear discriminant analysis. We also generated a
      ranked list of unidentified compounds that may contribute to the antimicrobial
      activity of yerba mate against MRSA. Here we utilized GC-MS data to implement an
      automated analysis that resulted in a ranked list of compounds that likely
      contribute to the antimicrobial activity of aqueous yerba mate extract against
      MRSA. 

PMID- 25955848
TI  - In situ near-infrared (NIR) versus high-throughput mid-infrared (MIR)
      spectroscopy to monitor biopharmaceutical production.
AB  - The development of biopharmaceutical manufacturing processes presents critical
      constraints, with the major constraint being that living cells synthesize these
      molecules, presenting inherent behavior variability due to their high sensitivity
      to small fluctuations in the cultivation environment. To speed up the development
      process and to control this critical manufacturing step, it is relevant to
      develop high-throughput and in situ monitoring techniques, respectively. Here,
      high-throughput mid-infrared (MIR) spectral analysis of dehydrated cell pellets
      and in situ near-infrared (NIR) spectral analysis of the whole culture broth were
      compared to monitor plasmid production in recombinant Escherichia coli cultures.
      Good partial least squares (PLS) regression models were built, either based on
      MIR or NIR spectral data, yielding high coefficients of determination (R(2)) and
      low predictive errors (root mean square error, or RMSE) to estimate host cell
      growth, plasmid production, carbon source consumption (glucose and glycerol), and
      by-product acetate production and consumption. The predictive errors for biomass,
      plasmid, glucose, glycerol, and acetate based on MIR data were 0.7 g/L, 9 mg/L,
      0.3 g/L, 0.4 g/L, and 0.4 g/L, respectively, whereas for NIR data the predictive
      errors obtained were 0.4 g/L, 8 mg/L, 0.3 g/L, 0.2 g/L, and 0.4 g/L,
      respectively. The models obtained are robust as they are valid for cultivations
      conducted with different media compositions and with different cultivation
      strategies (batch and fed-batch). Besides being conducted in situ with a
      sterilized fiber optic probe, NIR spectroscopy allows building PLS models for
      estimating plasmid, glucose, and acetate that are as accurate as those obtained
      from the high-throughput MIR setup, and better models for estimating biomass and
      glycerol, yielding a decrease in 57 and 50% of the RMSE, respectively, compared
      to the MIR setup. However, MIR spectroscopy could be a valid alternative in the
      case of optimization protocols, due to possible space constraints or high costs
      associated with the use of multi-fiber optic probes for multi-bioreactors. In
      this case, MIR could be conducted in a high-throughput manner, analyzing hundreds
      of culture samples in a rapid and automatic mode. 

PMID- 25955850
TI  - Class-DE Ultrasound Transducer Driver for HIFU Therapy.
AB  - This paper presents a practical implementation of an integrated MRI-compatible
      CMOS amplifier capable of directly driving a piezoelectric ultrasound transducer
      suitable for high-intensity focused ultrasound (HIFU) therapy. The amplifier
      operates in Class DE mode without the need for an output matching network. The
      integrated amplifier has been implemented with the AMS AG H35 CMOS process. A
      class DE amplifier design methodology for driving unmatched piezoelectric loads
      is presented along with simulation and experimental results. The proposed design
      achieves approximately 90% efficiency with over 800 mW of output power at 1010
      kHz. The total die area including pads is 2 mm(2). Compatibility with MRI was
      validated with B1 imaging of a phantom and the amplifier circuit.

PMID- 25955849
TI  - Viral Dose and Immunosuppression Modulate the Progression of Acute BVDV-1
      Infection in Calves: Evidence of Long Term Persistence after Intra-Nasal
      Infection.
AB  - Bovine viral diarrhoea virus (BVDV) infection of cattle causes a diverse range of
      clinical outcomes from being asymptomatic, or a transient mild disease, to
      producing severe cases of acute disease leading to death. Four groups of calves
      were challenged with a type 1 BVDV strain, originating from a severe outbreak of
      BVDV in England, to study the effect of viral dose and immunosuppression on the
      viral replication and transmission of BVDV. Three groups received increasing
      amounts of virus: Group A received 10(2.55)TCID50/ml, group B 10(5.25)TCID50/ml
      and group C 10(6.7)TCID 50/ml. A fourth group (D) was inoculated with a medium
      dose (10(5.25)TCID50/ml) and concomitantly treated with dexamethasone (DMS) to
      assess the effects of chemically induced immunosuppression. Naive calves were
      added as sentinel animals to assess virus transmission. The outcome of infection
      was dose dependent with animals given a higher dose developing severe disease and
      more pronounced viral replication. Despite virus being shed by the low-dose
      infection group, BVD was not transmitted to sentinel calves. Administration of
      dexamethasone (DMS) resulted in more severe clinical signs, prolonged viraemia
      and virus shedding. Using PCR techniques, viral RNA was detected in blood,
      several weeks after the limit of infectious virus recovery. Finally, a recently
      developed strand-specific RT-PCR detected negative strand viral RNA, indicative
      of actively replicating virus, in blood samples from convalescent animals, as
      late as 85 days post inoculation. This detection of long term replicating virus
      may indicate the way in which the virus persists and/or is reintroduced within
      herds.

PMID- 25955851
TI  - Review of Robotic Technology for Stereotactic Neurosurgery.
AB  - The research of stereotactic apparatus to guide surgical devices began in 1908,
      yet a major part of today's stereotactic neurosurgeries still rely on
      stereotactic frames developed almost half a century ago. Robots excel at handling
      spatial information, and are, thus, obvious candidates in the guidance of
      instrumentation along precisely planned trajectories. In this review, we
      introduce the concept of stereotaxy and describe a standard stereotactic
      neurosurgery. Neurosurgeons' expectations and demands regarding the role of
      robots as assistive tools are also addressed. We list the most successful robotic
      systems developed specifically for or capable of executing stereotactic
      neurosurgery. A critical review is presented for each robotic system, emphasizing
      the differences between them and detailing positive features and drawbacks. An
      analysis of the listed robotic system features is also undertaken, in the context
      of robotic application in stereotactic neurosurgery. Finally, we discuss the
      current perspective, and future directions of a robotic technology in this field.
      All robotic systems follow a very similar and structured workflow despite the
      technical differences that set them apart. No system unequivocally stands out as
      an absolute best. The trend of technological progress is pointing toward the
      development of miniaturized cost-effective solutions with more intuitive
      interfaces. 

PMID- 25955852
TI  - Pinning Control Strategies for Synchronization of Linearly Coupled Neural
      Networks With Reaction-Diffusion Terms.
AB  - Two types of coupled neural networks with reaction-diffusion terms are considered
      in this paper. In the first one, the nodes are coupled through their states. In
      the second one, the nodes are coupled through the spatial diffusion terms. For
      the former, utilizing Lyapunov functional method and pinning control technique,
      we obtain some sufficient conditions to guarantee that network can realize
      synchronization. In addition, considering that the theoretical coupling strength
      required for synchronization may be much larger than the needed value, we propose
      an adaptive strategy to adjust the coupling strength for achieving a suitable
      value. For the latter, we establish a criterion for synchronization using the
      designed pinning controllers. It is found that the coupled reaction-diffusion
      neural networks with state coupling under the given linear feedback pinning
      controllers can realize synchronization when the coupling strength is very large,
      which is contrary to the coupled reaction-diffusion neural networks with spatial
      diffusion coupling. Moreover, a general criterion for ensuring network
      synchronization is derived by pinning a small fraction of nodes with adaptive
      feedback controllers. Finally, two examples with numerical simulations are
      provided to demonstrate the effectiveness of the theoretical results. 

PMID- 25955853
TI  - Kernel-Based Least Squares Temporal Difference With Gradient Correction.
AB  - A least squares temporal difference with gradient correction (LS-TDC) algorithm
      and its kernel-based version kernel-based LS-TDC (KLS-TDC) are proposed as policy
      evaluation algorithms for reinforcement learning (RL). LS-TDC is derived from the
      TDC algorithm. Attributed to TDC derived by minimizing the mean-square projected
      Bellman error, LS-TDC has better convergence performance. The least squares
      technique is used to omit the size-step tuning of the original TDC and enhance
      robustness. For KLS-TDC, since the kernel method is used, feature vectors can be
      selected automatically. The approximate linear dependence analysis is performed
      to realize kernel sparsification. In addition, a policy iteration strategy
      motivated by KLS-TDC is constructed to solve control learning problems. The
      convergence and parameter sensitivities of both LS-TDC and KLS-TDC are tested
      through on-policy learning, off-policy learning, and control learning problems.
      Experimental results, as compared with a series of corresponding RL algorithms,
      demonstrate that both LS-TDC and KLS-TDC have better approximation and
      convergence performance, higher efficiency for sample usage, smaller burden of
      parameter tuning, and less sensitivity to parameters. 

PMID- 25955854
TI  - Optimal MAP Parameters Estimation in STAPLE Using Local Intensity Similarity
      Information.
AB  - In recent years, fusing segmentation results obtained based on multiple template
      images has become a standard practice in many medical imaging applications. Such
      multiple-templates-based methods are found to provide more reliable and accurate
      segmentations than the single-template-based methods. In this paper, we present a
      new approach for learning prior knowledge about the performance parameters of
      template images using the local intensity similarity information; we also propose
      a methodology to incorporate that prior knowledge through the estimation of the
      optimal MAP parameters. The proposed method is evaluated in the context of
      segmentation of structures in the brain magnetic resonance images by comparing
      our results with some of the state-of-the-art segmentation methods. These
      experiments have clearly demonstrated the advantages of learning and
      incorporating prior knowledge about the performance parameters using the proposed
      method. 

PMID- 25955855
TI  - Automatic localization of the anterior commissure, posterior commissure, and
      midsagittal plane in MRI scans using regression forests.
AB  - Localizing the anterior and posterior commissures (AC/PC) and the midsagittal
      plane (MSP) is crucial in stereotactic and functional neurosurgery, human brain
      mapping, and medical image processing. We present a learning-based method for
      automatic and efficient localization of these landmarks and the plane using
      regression forests. Given a point in an image, we first extract a set of
      multiscale long-range contextual features. We then build random forests models to
      learn a nonlinear relationship between these features and the probability of the
      point being a landmark or in the plane. Three-stage coarse-to-fine models are
      trained for the AC, PC, and MSP separately using downsampled by 4, downsampled by
      2, and the original images. Localization is performed hierarchically, starting
      with a rough estimation that is progressively refined. We evaluate our method
      using a leave-one-out approach with 100 clinical T1-weighted images and compare
      it to state-of-the-art methods including an atlas-based approach with six
      nonrigid registration algorithms and a model-based approach for the AC and PC,
      and a global symmetry-based approach for the MSP. Our method results in an
      overall error of 0.55 +/-0.30 mm for AC, 0.56 +/-0.28 mm for PC, 1.08( degrees )
      +/-0.66 in the plane's normal direction, and 1.22 +/-0.73 voxels in average
      distance for MSP; it performs significantly better than four registration
      algorithms and the model-based method for AC and PC, and the global symmetry
      based method for MSP. We also evaluate the sensitivity of our method to image
      quality and parameter values. We show that it is robust to asymmetry, noise, and
      rotation. Computation time is 25 s. 

PMID- 25955856
TI  - K+ excretion: the other purpose for puddling behavior in Japanese Papilio
      butterflies.
AB  - To elucidate the purpose of butterfly puddling, we measured the amounts of Na+,
      K+, Ca2+, and Mg2+ that were absorbed or excreted during puddling by male
      Japanese Papilio butterflies through a urine test. All of the butterflies that
      sipped water with a Na+ concentration of 13 mM absorbed Na+ and excreted K+,
      although certain butterflies that sipped solutions with high concentrations of
      Na+ excreted Na+. According to the Na+ concentrations observed in naturally
      occurring water sources, water with a Na+ concentration of up to 10 mM appears to
      be optimal for the health of male Japanese Papilio butterflies. The molar ratio
      of K+ to Na+ observed in leaves was 43.94 and that observed in flower nectars was
      10.93. The Na+ amount in 100 g of host plant leaves ranged from 2.11 to 16.40 mg,
      and the amount in 100 g of flower nectar ranged from 1.24 to 108.21 mg.
      Differences in host plants did not explain the differences in the frequency of
      puddling observed for different Japanese Papilio species. The amounts of Na+, K+,
      Ca2+, and Mg2+ in the meconium of both male and female butterflies were also
      measured, and both males and females excreted more K+ than the other three ions.
      Thus, the fluid that was excreted by butterflies at emergence also had a role in
      the excretion of the excessive K+ in their bodies. The quantities of Na+ and K+
      observed in butterfly eggs were approximately 0.50 MUg and 4.15 MUg,
      respectively; thus, female butterflies required more K+ than male butterflies.
      Therefore, female butterflies did not puddle to excrete K+. In conclusion, the
      purpose of puddling for male Papilio butterflies is not only to absorb Na+ to
      correct deficiencies but also to excrete excessive K+. 

PMID- 25955858
TI  - Binarization With Boosting and Oversampling for Multiclass Classification.
AB  - Using a set of binary classifiers to solve multiclass classification problems has
      been a popular approach over the years. The decision boundaries learnt by binary
      classifiers (also called base classifiers) are much simpler than those learnt by
      multiclass classifiers. This paper proposes a new classification framework,
      termed binarization with boosting and oversampling (BBO), for efficiently solving
      multiclass classification problems. The new framework is devised based on the one
      versus-all (OVA) binarization technique. Unlike most previous work, BBO employs
      boosting for solving the hard-to-learn instances and oversampling for handling
      the class-imbalance problem arising due to OVA binarization. These two features
      make BBO different from other existing works. Our new framework has been tested
      extensively on several multiclass supervised and semi-supervised classification
      problems using five different base classifiers, including neural networks, C4.5,
      k -nearest neighbor, repeated incremental pruning to produce error reduction,
      support vector machine, random forest, and learning with local and global
      consistency. Experimental results show that BBO can exhibit better performance
      compared to its counterparts on supervised and semi-supervised classification
      problems. 

PMID- 25955857
TI  - Dicer-Dependent Biogenesis of Small RNAs and Evidence for MicroRNA-Like RNAs in
      the Penicillin Producing Fungus Penicillium chrysogenum.
AB  - MicroRNAs (miRNAs) are non-coding small RNAs (sRNAs) that regulate gene
      expression in a wide range of eukaryotes. In this study, we analyzed regulatory
      sRNAs in Penicillium chrysogenum, the industrial producer of the beta-lactam
      antibiotic penicillin. To identify sRNAs and microRNA-like RNAs (milRNAs) on a
      global approach, two sRNA sequencing libraries were constructed. One library was
      created with pooled total RNA, obtained from twelve differently grown cultures
      (RNA Mix), and the other with total RNA from a single submerged cultivation
      (?ku70FRT2). Illumina sequencing of both RNA libraries produced 84,322,825 mapped
      reads. To distinguish between Dicer-dependent and independent sRNA formation, we
      further constructed two single dicer gene mutants (?dcl2 and ?dcl1) and a dicer
      double mutant (?dcl2?dcl1) and analyzed an sRNA library from the Dicer-deficient
      double-mutant. We identified 661 Dicer-dependent loci and in silico prediction
      revealed 34 milRNAs. Northern blot hybridization of two milRNAs provided evidence
      for mature milRNAs that are processed either in a complete or partial Dicer
      dependent manner from an RNA precursor. Identified milRNAs share typical
      characteristics of previously discovered fungal milRNAs, like a strong preference
      for a 5' uracil and the typical length distribution. The detection of potential
      milRNA target sites in the genome suggests that milRNAs might play a role in
      posttranscriptional gene regulation. Our data will further increase our knowledge
      of sRNA dependent gene regulation processes, which is an important prerequisite
      to develop more effective strategies for improving industrial fermentations with
      P. chrysogenum. 

PMID- 25955859
TI  - A Novel Extreme Learning Control Framework of Unmanned Surface Vehicles.
AB  - In this paper, an extreme learning control (ELC) framework using the single
      hidden-layer feedforward network (SLFN) with random hidden nodes for tracking an
      unmanned surface vehicle suffering from unknown dynamics and external
      disturbances is proposed. By combining tracking errors with derivatives, an error
      surface and transformed states are defined to encapsulate unknown dynamics and
      disturbances into a lumped vector field of transformed states. The lumped
      nonlinearity is further identified accurately by an extreme-learning-machine
      based SLFN approximator which does not require a priori system knowledge nor
      tuning input weights. Only output weights of the SLFN need to be updated by
      adaptive projection-based laws derived from the Lyapunov approach. Moreover, an
      error compensator is incorporated to suppress approximation residuals, and
      thereby contributing to the robustness and global asymptotic stability of the
      closed-loop ELC system. Simulation studies and comprehensive comparisons
      demonstrate that the ELC framework achieves high accuracy in both tracking and
      approximation. 

PMID- 25955860
TI  - A Stochastic Framework for Robust Fuzzy Filtering and Analysis of Signals-Part I.
AB  - There are numerous applications across all the spectrum of scientific areas that
      demand the mathematical study of signals/data. The two typical study areas of
      theoretical research on signal/data processing are of modeling (i.e.,
      understanding of signal's behavior) and of analysis (i.e., evaluation of given
      signal for finding its association to existing signal models). The objective of
      this paper is to provide a stochastic framework to design both fuzzy filtering
      and analysis algorithms in a unified manner. The signals are modeled via linear
      in-parameters models (e.g., a type of Takagi-Sugeno fuzzy model) based on
      variational Bayes (VB) methodology. This gives rise to the "negative free energy
      maximizing" filtering algorithm. The issue of intractability was handled first by
      carefully choosing the priors as conjugate to the likelihood and then by using
      Stirling approximation for the Gamma function. This paper highlighted that it was
      analytically possible to maximize the information theoretic quantity, "mutual
      information," exactly in the same manner as maximizing "negative free energy" in
      VB methodology. This gives rise to the "variational information maximizing"
      analysis algorithm. The robustness of the methodology against data outliers is
      achieved by modeling the noises with Student- t distributions. The framework
      takes into account the inputs noises as well apart from the usually considered
      output noise. The robustness of the adaptive filtering algorithm against noise is
      shown by a deterministic analysis where an upper bound on the magnitude of
      estimation errors is derived. 

PMID- 25955861
TI  - High Capacity Reversible Data Hiding in Encrypted Images by Patch-Level Sparse
      Representation.
AB  - Reversible data hiding in encrypted images has attracted considerable attention
      from the communities of privacy security and protection. The success of the
      previous methods in this area has shown that a superior performance can be
      achieved by exploiting the redundancy within the image. Specifically, because the
      pixels in the local structures (like patches or regions) have a strong
      similarity, they can be heavily compressed, thus resulting in a large hiding
      room. In this paper, to better explore the correlation between neighbor pixels,
      we propose to consider the patch-level sparse representation when hiding the
      secret data. The widely used sparse coding technique has demonstrated that a
      patch can be linearly represented by some atoms in an over-complete dictionary.
      As the sparse coding is an approximation solution, the leading residual errors
      are encoded and self-embedded within the cover image. Furthermore, the learned
      dictionary is also embedded into the encrypted image. Thanks to the powerful
      representation of sparse coding, a large vacated room can be achieved, and thus
      the data hider can embed more secret messages in the encrypted image. Extensive
      experiments demonstrate that the proposed method significantly outperforms the
      state-of-the-art methods in terms of the embedding rate and the image quality. 

PMID- 25955863
TI  - CCL2, CXCL8, CXCL9 and CXCL10 serum levels increase with age but are not altered
      by treatment with hydroxychloroquine in patients with osteoarthritis of the
      knees.
AB  - AIM: Osteoarthritis (OA) is a major cause of morbidity and incapacity in the
      elderly. This study evaluates serum levels of the chemokines CCL2, CXCL8, CXCL9,
      and CXCL10 in 16 patients with primary OA of the knees, and investigates how
      treatment with hydroxychloroquine (HCQ) for 4 months affects these chemokine
      levels. METHOD: Thirteen elderly patients received a placebo. Healthy control
      groups consisted of 10 elderly individuals (age > 60 years) with no clinical or
      radiological evidence of OA (CT-O), and 10 young adult individuals, (CT-Y group,
      age < 40 years). RESULTS: The CT-Y group presented lower levels of all chemokines
      studied, in comparison to the other groups. HCQ treatment did not alter the serum
      levels of CCL2 (P = 0.80), CXCL8 (P = 0.76), CXCL9 (P = 0.95) and CXCL10 (P =
      0.74) in OA patients. CONCLUSION: Hydroxychloroquine treatment did not alter the
      serum levels of CCL2, CXCL8, CXCL9 or CXCL10 in patients with OA of the knees,
      although increased serum levels correlated with aging for all subjects, including
      controls.

PMID- 25955864
TI  - Controlled motion of electrically neutral microparticles by pulsed direct
      current.
AB  - A controlled motion of electrically neutral microparticles in a conductive liquid
      at high temperatures has not yet been realized under the uniform direct electric
      current field. We propose a simple method, which employs pulsed direct current to
      a conductive liquid metal containing low-conductivity objects at high
      temperature. The electric current enables the low-conductivity particles to pass
      from the centre towards the various surfaces of the high-conductivity liquid
      metal. Most interestingly, the directionality of microparticles can be controlled
      and their speed can be easily regulated by adjusting pulsed current density. We
      find that the movement may arise from the configuration of electrical domains
      which generates a driving force which exceeds the force of gravity and viscous
      friction. All of these features are of potential benefit in separating the
      particles of nearly equal density but distinctly different electrical
      conductivities, and also offer considerable promise for the precise and selective
      positioning of micro-objects or the controlled motion of minute quantities of
      surrounding fluids. 

PMID- 25955862
TI  - The mammalian lectin galectin-8 induces RANKL expression, osteoclastogenesis, and
      bone mass reduction in mice.
AB  - Skeletal integrity is maintained by the co-ordinated activity of osteoblasts, the
      bone-forming cells, and osteoclasts, the bone-resorbing cells. In this study, we
      show that mice overexpressing galectin-8, a secreted mammalian lectin of the
      galectins family, exhibit accelerated osteoclasts activity and bone turnover,
      which culminates in reduced bone mass, similar to cases of postmenopausal
      osteoporosis and cancerous osteolysis. This phenotype can be attributed to a
      direct action of galectin-8 on primary cultures of osteoblasts that secrete the
      osteoclastogenic factor RANKL upon binding of galectin-8. This results in
      enhanced differentiation into osteoclasts of the bone marrow cells co-cultured
      with galectin-8-treated osteoblasts. Secretion of RANKL by galectin-8-treated
      osteoblasts can be attributed to binding of galectin-8 to receptor complexes that
      positively (uPAR and MRC2) and negatively (LRP1) regulate galectin-8 function.
      Our findings identify galectins as new players in osteoclastogenesis and bone
      remodeling, and highlight a potential regulation of bone mass by animal lectins. 

PMID- 25955865
TI  - High Plasma Levels of Neuropeptide Y Correlate With Good Clinical Outcome But are
      not Correlated to Cerebral Blood Flow or Vasospasm After Subarachnoid Hemorrhage.
AB  - BACKGROUND AND PURPOSE: Delayed cerebral ischemia (DCI) is a serious and frequent
      complication following subarachnoid hemorrhage. Treatments with convincing effect
      are lacking and the pathophysiology behind DCI remains poorly understood.
      Neuropeptide Y (NPY) is a potent endogenous vasoconstrictor and a role of NPY in
      the development of DCI has been proposed. This study investigated the
      relationship between plasma-NPY and cerebral blood flow (CBF), cerebral
      vasospasm, DCI, and clinical outcome. METHODS: In 90 patients with subarachnoid
      hemorrhage, NPY was measured in peripheral blood days 2 to 11. Any occurrence of
      DCI was recorded and CBF was quantified day 3 and day 8 using computed tomography
      (CT) perfusion. CT angiography was performed day 8. Clinical outcome was assessed
      after 3 months. RESULTS: No correlation was found between plasma-NPY and CBF or
      angiographic vasospasm. The correlation between reduced plasma-NPY and DCI
      reached borderline statistical significance (P=0.05). Increased levels of NPY
      measured on days 2 to 4 were correlated to good outcome (P=0.006). CONCLUSIONS:
      Our findings in peripheral blood were not supportive of a causal relationship
      between NPY secretion and DCI. Although high levels of plasma-NPY were correlated
      with good clinical outcome, NPY did not show promise as a clinically useful
      biomarker.

PMID- 25955866
TI  - The Opioid-sparing Effect of Intraoperative Dexmedetomidine Infusion After
      Craniotomy.
AB  - BACKGROUND: We conducted a randomized trial to evaluate the opioid-sparing effect
      of an intraoperative infusion of dexmedetomidine (DEX) after craniotomy. METHODS:
      Sixty adult patients scheduled for craniotomy were divided randomly into group A
      (DEX infusion at 0.5 MUg/kg/h for 10 min and then adjusted to 0.2 to 0.5 MUg/kg/h
      from tracheal intubation to incision suturing) and group B (0.9% saline
      infusion). Additional intravenous injections and patient-controlled analgesia
      with morphine were used to control postoperative pain for verbal Numerical Rating
      Scale scores >4. Cumulative morphine consumption, Numerical Rating Scale pain
      score, and the Ramsay Sedation Scale score were evaluated at 1, 2, 4, 6, 8, 12,
      and 24 hours; the incidence of postoperative nausea and vomiting, agitation, and
      respiratory depression were recorded at 24 hours after surgery. RESULTS:
      Postoperative pain scores within 12 hours and Ramsay Sedation Scale scores within
      6 hours of surgery were both significantly lower in group A than in group B
      (P<0.001). Patients in group A required 54.4%, 43.3%, and 31.4% less cumulative
      morphine consumption during the first 4, 12, and 24 hours, respectively. No
      patient in group A and 5 patients in group B presented agitation within 1 hour
      after surgery. Three patients in group A and 9 patients in group B showed
      pruritus (P<0.001). CONCLUSIONS: An intraoperative infusion of DEX reduced
      cumulative morphine consumption and adverse effects after craniotomy.

PMID- 25955867
TI  - Severe disseminated primary herpes simplex infection as skin manifestation of
      GATA2 deficiency.

PMID- 25955868
TI  - Genetic variants in the tumor necrosis factor-related apoptosis-inducing ligand
      and death receptor genes contribute to susceptibility to bladder cancer.
AB  - AIM: The aim of this study was to evaluate the role of polymorphisms of tumor
      necrosis factor-related apoptosis-inducing ligand (TRAIL) and death receptor
      (DR4) genes in bladder cancer susceptibility in a Turkish population. MATERIALS
      AND METHODS: The study group included 91 bladder cancer patients, while the
      control group comprised 139 individuals with no evidence of malignancy. Gene
      polymorphisms of TRAIL C1595T (rs1131580) and DR4 C626G (rs4871857) were
      genotyped by polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) analysis. RESULTS: The frequency of the TRAIL 1595 TT genotype was
      significantly lower in patients with bladder cancer compared to controls
      (p<0.001; odds ratios [OR]=0.143; 95% confidence interval [CI]=0.045-0.454). A
      significantly increased risk for developing bladder cancer was found for the
      group bearing a C allele for TRAIL C1595T polymorphism (p<0.001; OR=1.256; 95%
      CI=1.138-1.386). The observed genotype and allele frequencies of DR4 626 C/G in
      all groups were in agreement with the Hardy-Weinberg equilibrium (p=0.540).
      However, the frequency of DR4 GG genotype was found to be 2.1-fold increased in
      the bladder cancer patients with high-grade tumor, when compared to those having
      low-grade tumor (p=0.036). Additionally, combined genotype analysis showed that
      the frequency of TRAILCT-DR4GG was significantly higher in patients with bladder
      cancer in comparison with those of controls (p=0.037; OR=2.240; 95% CI=1.138
      1.386). CONCLUSIONS: Our study provides new evidence that TRAIL 1595 C allele may
      be used as a low-penetrant risk factor for bladder cancer development in a
      Turkish population. Otherwise, gene-gene interaction analysis revealed that the
      DR4GG genotype may have a predominant effect on the increased risk of bladder
      cancer over the TRAIL CT genotype.

PMID- 25955869
TI  - Ultrasonographic measured optic nerve sheath diameter as an accurate and quick
      monitor for changes in intracranial pressure.
AB  - OBJECT: Ultrasonographic measurement of the optic nerve sheath diameter (ONSD) is
      known to be an accurate monitor of elevated intracranial pressure (ICP). However,
      it is yet unknown whether fluctuations in ICP result in direct changes in ONSD.
      Therefore, the authors researched whether ONSD and ICP simultaneously change
      during tracheal manipulation in patients in the intensive care unit (ICU) who
      have suffered a traumatic brain injury (TBI). MATERIALS: The authors included 18
      ICP-monitored patients who had sustained TBI and were admitted to the ICU. They
      examined the optic nerve sheath by performing ultrasound before, during, and
      after tracheal manipulation, which is known to increase ICP. The correlation
      between ONSD and ICP measurements was determined, and the diagnostic performance
      of ONSD measurement was tested using receiver operating characteristic curve
      analysis. RESULTS: In all patients ICP increased above 20 mm Hg during
      manipulation of the trachea, and this increase was directly associated with a
      dilation of the ONSD of > 5.0 mm. After tracheal manipulation stopped, ICP as
      well as ONSD decreased immediately to baseline levels. The correlation between
      ICP and ONSD was high (R(2) = 0.80); at a cutoff of >= 5.0 mm ONSD, a sensitivity
      of 94%, a specificity of 98%, and an area under the curve of 0.99 (95% CI 0.97
      1.00) for detecting elevated ICP were determined. CONCLUSIONS: In patients who
      have sustained a TBI, ultrasonography of the ONSD is an accurate, simple, and
      rapid measurement for detecting elevated ICP as well as immediate changes in ICP.
      Therefore, it might be a useful tool to monitor ICP, especially in conditions in
      which invasive ICP monitoring is not available, such as at trauma scenes.

PMID- 25955870
TI  - Subcortical anatomy as an anatomical and functional landmark in insulo-opercular
      gliomas: implications for surgical approach to the insular region.
AB  - OBJECT: Little attention has been given to the functional challenges of the
      insular approach to the resection of gliomas, despite the potential damage of
      essential neural networks that underlie the insula. The object of this study is
      to analyze the subcortical anatomy of the insular region when infiltrated by
      gliomas, and compare it with the normal anatomy in nontumoral hemispheres.
      METHODS: Ten postmortem human hemispheres were dissected, with isolation of the
      inferior fronto-occipital fasciculus (IFOF) and the uncinate fasciculus.
      Probabilistic diffusion tensor imaging (DTI) tractography was used to analyze the
      subcortical anatomy of the insular region in 10 healthy volunteers and in 22
      patients with insular Grade II and Grade III gliomas. The subcortical anatomy of
      the insular region in these 22 insular gliomas was compared with the normal
      anatomy in 20 nontumoral hemispheres. RESULTS: In tumoral hemispheres, the
      distances between the peri-insular sulci and the lateral surface of the IFOF and
      uncinate fasciculus were enlarged (p < 0.05). Also in tumoral hemispheres, the
      IFOF was identified in 10 (90.9%) of 11 patients with an extent of resection less
      than 80%, and in 4 (36.4%) of 11 patients with an extent of resection equal to or
      greater than 80% (multivariate analysis: p = 0.03). CONCLUSIONS: Insular gliomas
      grow in the space between the lateral surface of the IFOF and uncinate fasciculus
      and the insular surface, displacing and compressing the tracts medially.
      Moreover, these tracts may be completely infiltrated by the tumor, with a total
      disruption of the bundles. In the current study, the identification of the IFOF
      with DTI tractography was significantly associated with the extent of tumor
      resection. If the IFOF is not identified preoperatively, there is a high
      probability of achieving a resection greater than 80%.

PMID- 25955871
TI  - Letter to the Editor: Trigeminal neuralgia.

PMID- 25955872
TI  - Nonsurgical acute traumatic subdural hematoma: what is the risk?
AB  - OBJECT: The Brain Trauma Foundation has published guidelines on the surgical
      management of traumatic subdural hematoma (SDH). However, no data exist on the
      proportion of patients with SDH that can be selected for conservative management
      and what is the outcome of these patients. The goals of this study were as
      follows: 1) to establish what proportion of patients are initially treated
      conservatively; 2) to determine what proportion of patients will deteriorate and
      require surgical evacuation; and 3) to identify risk factors associated with
      deterioration and delayed surgery. METHODS: All cases of acute traumatic SDH (869
      when inclusion criteria were met) presenting over a 4-year period were reviewed.
      For all conservatively treated SDH, the proportion of delayed surgical
      intervention and the Glasgow Outcome Scale score were taken as outcome measures.
      Multiple factors were compared between patients who required delayed surgery and
      patients without surgery. RESULTS: Of the 869 patients with acute traumatic SDH,
      646 (74.3%) were initially treated conservatively. A good outcome was achieved in
      76.7% of the patients. Only 6.5% eventually required delayed surgery, and the
      median delay for surgery was 9.5 days. Factors associated with deterioration were
      as follows: 1) thicker SDH (p<0.001); 2) greater midline shift (p<0.001); 3)
      location at the convexity (p=0.001); 4) alcohol abuse (p=0.0260); and 5) history
      of falls (p=0.018). There was no significant difference in regard to age, sex,
      Glasgow Coma Scale score, Injury Severity Score, abnormal coagulation, use of
      blood thinners, and presence of cerebral atrophy or white matter disease.
      CONCLUSIONS: The majority of patients with SDH are treated conservatively. Of
      those, only 6.5% later required surgery, for raised intracranial pressure or SDH
      progression. Patients at risk can be identified and followed more carefully.

PMID- 25955873
TI  - Development of the Metronomic Biofeedback Pump for leptomeningeal carcinomatosis:
      technical note.
AB  - Patients with leptomeningeal carcinomatosis face a particularly grim prognosis.
      Current treatment consists of intrathecal delivery of methotrexate (MTX) or
      cytosine arabinoside (Ara-C) via Ommaya reservoir or lumbar puncture. Yet despite
      these interventions, the median survival after diagnosis is only 4-7 months. To
      address inherent shortcomings of current treatments and provide a more effective
      therapeutic approach, the Pharmaco-Kinesis Corporation has developed a novel type
      of implantable pump capable of delivering intrathecal chemotherapy (i.e., MTX) in
      a metronomic fashion with electronic feedback. The Metronomic Biofeedback Pump
      (MBP) consists of 3 components: 1) a 2-lumen catheter; 2) a microfluidic delivery
      pump with 2 reservoirs; and 3) a spectrophotometer monitoring MTX concentrations
      in the CSF. Using an animal model of intraventricular drug delivery, the authors
      demonstrate that the MBP can reliably deliver volumes of 500 MUl/min,
      consistently measure real-time intrathecal MTX concentrations via CSF aspiration,
      and provide biofeedback with the possibility of instant control and delivery
      adjustments. Therefore, this novel approach to chemotherapy minimizes toxic drug
      levels and ensures continuous exposure at precisely adjusted, individualized
      therapeutic levels. Altogether, application of the MBP is expected to increase
      survival of patients with leptomeningeal carcinomatosis, and appropriate Phase I
      and II trials are pending. 

PMID- 25955874
TI  - Treatment biases in traumatic neurosurgical care: a retrospective study of the
      Nationwide Inpatient Sample from 1998 to 2009.
AB  - OBJECT: This study was designed to assess the relationship between insurance
      status and likelihood of receiving a neurosurgical procedure following admission
      for either extraaxial intracranial hemorrhage or spinal vertebral fracture.
      METHODS: A retrospective analysis of the Nationwide Inpatient Sample (NIS; 1998
      2009) was performed. Cases of traumatic extraaxial intracranial hematoma and
      spinal vertebral fracture were identified using International Classification of
      Diseases, Ninth Revision (ICD-9) diagnosis codes. Within this cohort, those
      patients receiving a craniotomy or spinal fusion and/or decompression in the
      context of an admission for traumatic brain or spine injury, respectively, were
      identified using the appropriate ICD-9 procedure codes. RESULTS: A total of
      190,412 patients with extraaxial intracranial hematoma were identified between
      1998 and 2009. Within this cohort, 37,434 patients (19.7%) received a craniotomy.
      A total of 477,110 patients with spinal vertebral fracture were identified. Of
      these, 37,302 (7.8%) received a spinal decompression and/or fusion. On
      multivariate analysis controlling for patient demographics, severity of injuries,
      comorbidities, hospital volume, and hospital characteristics, uninsured patients
      had a reduced likelihood of receiving a craniotomy (odds ratio [OR] 0.76, 95%
      confidence interval [CI] 0.71-0.82) and spinal fusion (OR 0.67, 95% CI 0.64-0.71)
      relative to insured patients. This statistically significant trend persisted when
      uninsured and insured patients were matched on the basis of mortality propensity
      score. Uninsured patients demonstrated an elevated risk-adjusted mortality rate
      relative to insured patients in cases of extraaxial intracranial hematoma. Among
      patients with spinal injury, mortality rates were similar between patients with
      and without insurance. CONCLUSIONS: In this study, uninsured patients were
      consistently less likely to receive a craniotomy or spinal fusion for traumatic
      intracranial extraaxial hemorrhage and spinal vertebral fracture, respectively.
      This difference persisted after accounting for overall injury severity and
      patient access to high- or low-volume treatment centers, and potentially reflects
      a resource allocation bias against uninsured patients within the hospital
      setting. This information adds to the growing literature detailing the benefits
      of health reform initiatives seeking to expand access for the uninsured.

PMID- 25955876
TI  - Support for Obamacare?

PMID- 25955875
TI  - Gamma Knife radiosurgery for facial nerve schwannomas: a multicenter study.
AB  - OBJECT: Facial nerve schwannomas (FNSs) are rare intracranial tumors, and the
      optimal management of these tumors remains unclear. Resection can be undertaken,
      but the tumor's intimate association with the facial nerve makes resection with
      neurological preservation quite challenging. Stereotactic radiosurgery (SRS) has
      been used to treat FNSs, and this study evaluates the outcome of this approach.
      METHODS: At 8 medical centers participating in the North American Gamma Knife
      Consortium (NAGKC), 42 patients undergoing SRS for an FNS were identified, and
      clinical and radiographic data were obtained for these cases. Males outnumbered
      females at a ratio of 1.2:1, and the patients' median age was 48 years (range 11
      76 years). Prior resection was performed in 36% of cases. The mean tumor volume
      was 1.8 cm(3), and a mean margin dose of 12.5 Gy (range 11-15 Gy) was delivered
      to the tumor. RESULTS: At a median follow-up of 28 months, tumor control was
      achieved in 36 (90%) of the 40 patients with reliable radiographic follow-up.
      Actuarial tumor control was 97%, 97%, 97%, and 90% at 1, 2, 3, and 5 years
      postradiosurgery. Preoperative facial nerve function was preserved in 38 of 42
      patients, with 60% of evaluable patients having House-Brackmann scores of 1 or 2
      at last follow-up. Treated patients with a House-Brackmann score of 1 to 3 were
      more likely to demonstrate this level of facial nerve function at last evaluation
      (OR 6.09, 95% CI 1.7-22.0, p = 0.006). Avoidance of temporary or permanent
      neurological symptoms was more likely to be achieved in patients who received a
      tumor margin dose of 12.5 Gy or less (log-rank test, p = 0.024) delivered to a
      tumor of <= 1 cm(3) in volume (log-rank test, p = 0.01). CONCLUSIONS:
      Stereotactic radiosurgery resulted in tumor control and neurological preservation
      in most FNS patients. When the tumor is smaller and the patient exhibits
      favorable normal facial nerve function, SRS portends a better result. The authors
      believe that early, upfront SRS may be the treatment of choice for small FNSs,
      but it is an effective salvage treatment for residual/recurrent tumor that remain
      or progress after resection.

PMID- 25955877
TI  - Vascularized rotational temporal bone flap for repair of anterior skull base
      defects: a novel operative technique.
AB  - Repair of anterior skull base defects with vascularized grafts poses a
      significant challenge, given the location and small number of adequately sized
      vessels for free-flap anastomosis. This is particularly the case in the setting
      of redo surgery or in patients with preexisting soft-tissue trauma. Even more
      difficult is achieving a vascularized bone flap closure of such bony defects. The
      authors report a novel technique involving a rotational temporal bone flap with a
      temporalis muscle vascularized pedicle, which was used to repair an anterior
      fossa bony and soft-tissue defect created by recurrent malignancy. A 55-year-old
      man with history of scalp avulsion during a motor vehicle accident, anterior
      fossa/nasopharyngeal malignant neuroendocrine carcinoma postresection, and bone
      flap infection presented with a recurrence of his skull base malignancy. The
      tumor was located in the anterior fossa, extending interhemispherically and down
      through the cribriform plate, ethmoid air cells, and extending into the
      nasopharyngeal cavity. Resection of the recurrent tumor was performed. The bony
      defect in the anterior skull base was repaired with a novel vascularized
      rotational temporal bone flap, with acceptable separation of the nasopharynx from
      the intracranial cavity. The vascularized rotational temporal bone flap, in which
      a temporalis muscle pedicle is used, provides a novel and easily accessible means
      of vascularized bone closure of anterior skull base defects without the need for
      microsurgical free-flap grafting. 

PMID- 25955878
TI  - Atypical Marginal Zone Hyperplasia Is a Mimic for Lymphoma in Pediatric
      Transplant Recipients: Report of Two Patients.
AB  - Atypical marginal zone hyperplasia (AMZH) of mucosa-associated lymphoid tissue
      (MALT) closely resembles lymphoma in that it shows expansion of the marginal
      zones with prominent intraepithelial B lymphocytes, is immunoglobulin light-chain
      restricted, and may show aberrant CD43 expression. However, unlike lymphoma, it
      does not show rearrangement of the immunoglobulin heavy chain gene
      (immunoglobulin H [IgH]) by polymerase chain reaction (PCR), and it behaves in a
      benign fashion. We identified AMZH in 2 pediatric solid organ transplant
      recipients who presented with adenotonsillar hypertrophy. To date, the patients
      have experienced a self-limited course in the absence of treatment or reduction
      of immunosuppression. Atypical marginal zone hyperplasia is a pitfall for
      posttransplant lymphoproliferative disorder and MALT lymphoma in the pediatric
      solid organ transplant population. In transplant patients with a lambda
      restricted B-cell clone and marginal zone hyperplasia in native MALT sites, PCR
      for IgH and IgK gene rearrangement is essential to prevent misdiagnosis. 

PMID- 25955879
TI  - Difunctionalization of Alkenes via the Visible-Light-Induced
      Trifluoromethylarylation/1,4-Aryl Shift/Desulfonylation Cascade Reactions.
AB  - A novel visible-light-induced trifluoromethylarylation/1,4-aryl
      shift/desulfonylation cascade reaction using CF3SO2Cl as CF3 source was
      described. The protocol provides an efficient approach for the synthesis of alpha
      aryl-beta-trifluoromethyl amides and/or CF3-containing oxindoles as well as the
      isoquinolinediones under benign conditions. 

PMID- 25955880
TI  - Competition between Intra- and Intermolecular Association of Chain Molecules with
      Water-like Solvent.
AB  - Fluid properties and phase behavior of systems such as glycol ethers, carboxylic
      acids, and proteins are affected by the competition between intra- and
      intermolecular hydrogen bonding. Here we study this competition by extending
      Wertheim's first-order thermodynamic perturbation theory to include
      intramolecular hydrogen bonding in chain molecules in the presence of an explicit
      water-like solvent. The theory derived here is found to be in good agreement with
      molecular simulation. It is shown that intramolecular association is most
      important for shorter chains at low temperature, low density, and high chain
      concentration. The theory is also extended into a density functional theory
      formalism to study the effect of intramolecular association on the structuring of
      the different segments of the molecules close to a hydrophobic surface.
      Intramolecular association is found to be enhanced close to the surface, with the
      total density of the system having the most effect on structuring close to the
      surface. 

PMID- 25955881
TI  - Thiadiazolo[3,4-c]pyridine as an Acceptor toward Fast-Switching Green Donor
      Acceptor-Type Electrochromic Polymer with Low Bandgap.
AB  - Thiadiazolo[3,4-c]pyridine (PT), an important analog of benzothiadiazole (BT),
      has most recently been explored as a novel electron acceptor. It exhibits more
      electron-accepting ability and other unique properties and potential advantages
      over BT, thus inspiring us to investigate PT-based donor-acceptor-type (D-A)
      conjugated polymer in electrochromics. Herein, PT was employed for the rational
      design of novel donor-acceptor-type systems to yield a neutral green
      electrochromic polymer poly(4,7-di(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)
      [1,2,5] thiadiazolo[3,4-c]pyridine) (PEPTE). PEPTE revealed a lower bandgap
      (Eg,ele=0.85 eV, Eg,opt=1.12 eV) than its BT analog and also favorable redox
      activity and stability. Furthermore, electrochromic kinetic studies demonstrated
      that PEPTE displayed higher coloration efficiency than BT analog, good optical
      memory, and very fast switching time (0.3 s at all three wavelengths), indicating
      that PT would probably be a promising choice for developing novel neutral green
      electrochromic polymers by matching with various donor units.

PMID- 25955882
TI  - Colloidal drug delivery systems: current status and future directions.
AB  - In this paper, we provide an overview an extensive range of colloidal drug
      delivery systems with special focus on vesicular and particulates systems that
      are being used in research or might be potentially useful as carriers systems for
      drug or active biomolecules or as cell carriers with application in the
      therapeutic field. We present some important examples of commercially available
      drug delivery systems with applications in research or in clinical fields. This
      class of systems is widely used due to excellent drug targeting, sustained and
      controlled release behavior, higher entrapment efficiency of drug molecules,
      prevention of drug hydrolysis or enzymatic degradation, and improvement of
      therapeutic efficacy. These characteristics help in the selection of suitable
      carrier systems for drug, cell, and gene delivery in different fields. 

PMID- 25955883
TI  - Ligand-Appended BBB-Targeted Nanocarriers (LABTNs).
AB  - Delivering therapeutics across the blood brain barrier (BBB) remains the rate
      limiting step in brain medicine research. Three main categories of endogenous
      transportation at BBB that can be used for targeting brain are carrier-mediated
      transport, active efflux transport, and receptor-mediated transport. Various
      approaches using nanocarriers such as liposomes, niosomes, micelles, and
      nanoparticles with manifested surface modifications using either covalent or
      noncovalent methods to append suitable ligands are being intensively explored to
      achieve drug delivery to the brain. Harvested ligands include peptide,
      glutathione, transferrin, and transferrin antibody, lectins, lactic acid, cholera
      toxin B, etc. In this review, we present recent insights into the development of
      safe and efficient brain drug delivery as well as recent advances in BBB
      targeting tactics including antibody-directed enzyme prodrug therapy, a biotin
      avidin conjugated system, and chimeric peptides. This review serves as an
      excellent source of knowledge for budding brain researchers. 

PMID- 25955884
TI  - Clostridium difficile infection: New insights into therapeutic options.
AB  - Clostridium difficile infection (CDI) is an important cause of mortality and
      morbidity in healthcare settings and represents a major social and economic
      burden. The major virulence determinants are large clostridial toxins, toxin A
      (TcdA) and toxin B (TcdB), encoded within the pathogenicity locus. Traditional
      therapies, such as metronidazole and vancomycin, frequently lead to a vicious
      circle of recurrences due to their action against normal human microbiome. New
      disease management strategies together with the development of novel therapeutic
      and containment approaches are needed in order to better control outbreaks and
      treat patients. This article provides an overview of currently available CDI
      treatment options and discusses the most promising therapies under development. 

PMID- 25955885
TI  - Exploiting Conjugated Polyelectrolyte Photophysics toward Monitoring Real-Time
      Lipid Membrane-Surface Interaction Dynamics at the Single-Particle Level.
AB  - Herein we report the real-time observation of the interaction dynamics between
      cationic liposomes flowing in solution and a surface-immobilized charged
      scaffolding formed by the deposition of conjugated polyanion poly[5-methoxy-2-(3
      sulfopropoxy)-1,4-phenylenevinylene (MPS-PPV) onto 100-nm-diameter SiO2
      nanoparticles (NPs). Contact of the freely floating liposomes with the polymer
      coated surfaces led to the formation of supported lipid bilayers (SLBs). The
      interaction of the incoming liposomes with MPS-PPV adsorbed on individual SiO2
      nanoparticles promoted the deaggregation of the polymer conformation and led to
      large emission intensity enhancements. Single-particle total internal reflection
      fluorescence microscopy studies exploited this phenomenon as a way to monitor the
      deformation dynamics of liposomes on surface-immobilized NPs. The MPS-PPV
      emission enhancement (up to 25-fold) reflected on the extent of membrane contact
      with the surface of the NP and was correlated with the size of the incoming
      liposome. The time required for the MPS-PPV emission to reach a maximum (ranging
      from 400 to 1000 ms) revealed the dynamics of membrane deformation and was also
      correlated with the liposome size. Cryo-TEM experiments complemented these
      results by yielding a structural view of the process. Immediately following the
      mixing of liposomes and NPs the majority of NPs had one or more adsorbed
      liposomes, yet the presence of a fully formed SLB was rare. Prolonged incubation
      of liposomes and NPs showed completely formed SLBs on all of the NPs, confirming
      that the liposomes eventually ruptured to form SLBs. We foresee that the single
      particle studies we report herein may be readily extended to study membrane
      dynamics of other lipids including cellular membranes in live cell studies and to
      monitor the formation of polymer-cushioned SLBs. 

PMID- 25955886
TI  - Automated Solution-Phase Synthesis of beta-1,4-Mannuronate and beta-1,4-Mannan.
AB  - The first automated solution-phase synthesis of beta-1,4-mannuronate and beta-1,4
      mannan oligomers has been accomplished by using a beta-directing C-5 carboxylate
      strategy. By utilizing fluorous-tag assisting purification after repeated
      reaction cycles, beta-1,4-mannuronate was synthesized up to a hexasaccharide with
      limited loading of a glycosyl donor (up to 3.5 equiv) for each glycosylation
      cycle due to the homogeneous solution-phase reaction condition. After a global
      reduction of the uronates, the beta-1,4-mannan hexasaccharide was obtained,
      thereby demonstrating a new approach to beta-mannan synthesis. 

PMID- 25955887
TI  - Perceived current and ideal body size in female undergraduates.
AB  - Body image dissatisfaction and disordered eating attitudes and behaviors are
      pervasive problems in Western society, particularly for females. The female "thin
      ideal" is a potent contributor to the growing discontent with the female body and
      research has shown that even females who are normal or underweight, perceive
      themselves as overweight. The goal of the current study was to examine correlates
      of body image satisfaction and the perception of the female body. One hundred and
      sixty six female undergraduates (Mean Age=21.40 years) completed self-report
      measures pertaining to disordered eating (EAT-26) and body dissatisfaction (BIQ
      and ABS). Body image perception and satisfaction were measured using ratings of
      female bodies on a weight perception scale (PFRS). Overall, disordered eating was
      related to a lower ideal body size and greater body dissatisfaction. In support
      of previous research, the most common ideal female body had a BMI categorized as
      underweight. Although females in the current sample reported an ideal that was
      smaller than their current size, participants underestimated their current body
      size, which, given the amount of dieting and weight pressure in present Western
      society, seems counterintuitive. It is possible that thin ideal portrayed in the
      media is increasingly different from and at odds with the average female body. 

PMID- 25955888
TI  - Perfectionism and disordered eating in overweight woman.
AB  - INTRODUCTION: Perfectionism constitutes a risk factor for the development of
      eating disorders. In overweight women, knowledge about the nature of this
      association is scarce. OBJECTIVES: To investigate the relationship between
      perfectionism, eating behaviors and affect in overweight women. METHODS: The
      Portuguese versions of the Eating Disorder Examination Questionnaire/EDEQ, the
      Multidimensional Perfectionism Questionnaire and the Profile of Mood States were
      administered to an outpatient sample of 276 women (mean age=43.85+/-11.89years;
      mean BMI=32.82+/-5.43kg/m(2)). RESULTS: Correlations between Socially Prescribed
      Perfectionism/SPP, EDEQ total (T) and its dimensional scores (Weight and Shape
      Concern and Dissatisfaction/WSCD, Eating Concern/EC, Dietary Restraint/DR) were
      significant (r>.30; p>.001). Self-Oriented Perfectionism/SOP was significantly
      correlated with EDEQ-T, WSCD and DR (r=.20). Participants with high (>M+SD) vs.
      low (<M-SD) SOP and SPP had significantly higher means in EDEQ-T, WSCD, EC and DR
      (p<.001). Linear regression showed that SPP was predictor of EDEQ-T and EC
      (p<.001). CONCLUSIONS: SPP and SOP are related to disordered eating in overweight
      women.

PMID- 25955889
TI  - Synthesis, Antimicrobial and Hypoglycemic Activities of Novel N-(1
      Adamantyl)carbothioamide Derivatives.
AB  - The reaction of 1-adamantyl isothiocyanate 4 with the various cyclic secondary
      amines yielded the corresponding N-(1-adamantyl)carbothioamides 5a-e, 6, 7, 8a-c
      and 9. Similarly, the reaction of 4 with piperazine and trans-2,5
      dimethylpiperazine in 2:1 molar ratio yielded the corresponding N,N'-bis(1
      adamantyl)piperazine-1,4-dicarbothioamides 10a and 10b, respectively. The
      reaction of N-(1-adamantyl)-4-ethoxycarbonylpiperidine-1-carbothioamide 8c with
      excess hydrazine hydrate yielded the target carbohydrazide 11, in addition to 4
      (1-adamantyl)thiosemicarbazide 12 as a minor product. The reaction of the
      carbohydrazide 11 with methyl or phenyl isothiocyanate followed by heating in
      aqueous sodium hydroxide yielded the 1,2,4-triazole analogues 14a and 14b. The
      reaction of the carbohydrazide 11 with various aromatic aldehydes yielded the
      corresponding N'-arylideneamino derivatives 15a-g. The compounds 5a-e, 6, 7, 8a
      c, 9, 10a, 10b, 14a, 14b and 15a-g were tested for in vitro antimicrobial
      activity against certain strains of pathogenic Gram-positive and Gram-negative
      bacteria and the yeast-like fungus Candida albicans. The compounds 5c, 5d, 5e, 6,
      7, 10a, 10b, 15a, 15f and 15g showed potent antibacterial activity against one or
      more of the tested microorganisms. The oral hypoglycemic activity of compounds
      5c, 6, 8b, 9, 14a and 15b was determined in streptozotocin (STZ)-induced diabetic
      rats. Compound 5c produced significant reduction of serum glucose levels,
      compared to gliclazide. 

PMID- 25955890
TI  - Hitting the sweet spot-glycans as targets of fungal defense effector proteins.
AB  - Organisms which rely solely on innate defense systems must combat a large number
      of antagonists with a comparably low number of defense effector molecules. As one
      solution of this problem, these organisms have evolved effector molecules
      targeting epitopes that are conserved between different antagonists of a specific
      taxon or, if possible, even of different taxa. In order to restrict the activity
      of the defense effector molecules to physiologically relevant taxa, these target
      epitopes should, on the other hand, be taxon-specific and easily accessible.
      Glycans fulfill all these requirements and are therefore a preferred target of
      defense effector molecules, in particular defense proteins. Here, we review this
      defense strategy using the example of the defense system of multicellular
      (filamentous) fungi against microbial competitors and animal predators. 

PMID- 25955891
TI  - Catalytic Asymmetric 1,4-Addition Reactions of Simple Alkylnitriles.
AB  - The development of catalytic asymmetric carbon-carbon bond-forming reactions of
      alkylnitriles that do not have an activating group at the alpha-position, under
      proton-transfer conditions, is a challenging research topic. Here, we report
      catalytic asymmetric direct-type 1,4-addition reactions of alkylnitriles with
      alpha,beta-unsaturated amides by using a catalytic amount of potassium
      hexamethyldisilazide (KHMDS) with a chiral macro crown ether. The desired
      reactions proceeded in high yields with good diastereo- and enantioselectivities.
      To our knowledge, this is the first example of catalytic asymmetric direct-type
      1,4-addition reaction of alkylnitriles without any activating group at the alpha
      position. 

PMID- 25955892
TI  - NEW ASPECTS REGARDING NEOADJUVANT RADIOCHEMOTHERAPY IN LOCALLY ADVANCED
      NONINFLAMMATORY BREAST CANCER AND PREDICTIVE FACTORS FOR A PATHOLOGIC COMPLETE
      REMISSION: IGCS-0016 Breast Cancer.

PMID- 25955893
TI  - MANAGEMENT OF MICROMETASTASIS FOUND ON SENTINEL LYMPH NODE BIOPSY USING OSNA IN
      PATIENTS DIAGNOSED WITH EARLY BREAST CANCER: IGCS-0021 Breast Cancer.

PMID- 25955894
TI  - SERIAL RESECTIONS IN METASTATIC BREAST CANCER: IGCS-0035 Breast Cancer.

PMID- 25955895
TI  - COSMETIC OUTCOME ASSESSMENT AFTER NEOADJUVANT RADIOCHEMOTHERAPY IN BREAST CANCER
      PATIENTS: IGCS-0036 Breast Cancer.

PMID- 25955896
TI  - NEOADYUVANT HORMONOTHERAPY IN LOCALLY ADVANCED BREAST CANCER, POSMENOPAUSIC WOMEN
      WITH HORMONAL RECEPTORS POSITIVE: IGCS-0049 Breast Cancer.

PMID- 25955897
TI  - TREATMENT AND OUTCOME OF STAGE I A1 SQUAMOUS CARCINOMA OF THE CERVIX: A
      CLINICOPATHOLOGIC STUDY OF 346 CASES: IGCS-0011 Cervical Cancer.

PMID- 25955898
TI  - APOPTOTIC PATHWAY OF ZINC ON CERVICAL CANCER CELL LINE: IGCS-0020 Cervical
      Cancer.

PMID- 25955900
TI  - CLINICAL OUTCOMES AND HEALTH-RELATED QUALITY OF LIFE OF PATIENTS WHO HAD
      UNDERGONE TOTAL LAPAROSCOPIC VERSUS TOTAL ROBOTIC RADICAL HYSTERECTOMY FOR
      CERVICAL CARCINOMA: IGCS-0024 Cervical Cancer.

PMID- 25955899
TI  - THE VALUE OF CYTOKERATIN 19 AND HUMAN PAPILLOMA VIRUS DNA AS MICROMETASTASIS
      MARKERS IN CERVICAL CANCER PATIENTS WITH INTERMEDIATE RISK FACTORS: IGCS-0022
      Cervical Cancer.

PMID- 25955901
TI  - ATYPICAL HEPATECTOMY FOR LIVER METASTASES FROM CERVICAL CANCER: IGCS-0029
      Cervical Cancer.

PMID- 25955902
TI  - HYPOXIA AND BIOMARKERS EXPRESSION IN CERVICAL CANCER (CC) AND HIGH GRADE SQUAMOUS
      INTRAEPITHELIAL LESIONS (HSIL): IGCS-0037 Cervical Cancer.

PMID- 25955904
TI  - SURVIVAL OF CERVICAL CANCER TYPE SQUAMOUS AND ADENOCARCINOMA IN PATIENTS FROM THE
      NATIONAL CANCER INSTITUTE, BETWEEN 2009-2013, CHILE: IGCS-0050 Cervical Cancer.

PMID- 25955903
TI  - ACCURACY OF 18 F-FDG PET/CT FOR THE DETECTION OF PARA-AORTIC LYMPH NODE
      METASTASIS IN PATIENTS WITH EARLY BULKY AND LOCALLY ADVANCED UTERINE CERVICAL
      CARCINOMA.FIRST NATIONAL EXPERIENCE: IGCS-0046 Cervical Cancer.

PMID- 25955905
TI  - UTERINE CERVICAL CANCER RECURRENCE PATTERN IN HIGUERAS HOSPITAL,TALCAHUANO -
      CHILE,BETWEEN 2003 AND 2014: IGCS-0052 Cervical Cancer.

PMID- 25955906
TI  - CYTOHISTOLOGICAL CORRELATION IN CPU HIGUERAS HOSPITAL, TALCAHUANO - CHILE,
      BETWEEN 2003 AND 2014.: IGCS-0054 Cervical Cancer.

PMID- 25955907
TI  - BIOMARKER ASSESSMENT IN CERVICAL UTERINE CANCER: IGCS-0055 Cervical Cancer.

PMID- 25955908
TI  - AVALIATION OF RESIDUAL DISEASE IN HYSTERECTOMY SPECIMENS AFTER CONIZATION IN
      WOMEN TREATED FOR SQUAMOUS MICROINVASIVE CARCINOMA OF THE UTERINE CERVIX: IGCS
      0064 Cervical Cancer.

PMID- 25955909
TI  - SURVIVAL IN CERVICAL CANCER PATIENTS TREATED BY MINIMALLY INVASIVE SURGERY: IGCS
      0066 Cervical Cancer.

PMID- 25955910
TI  - DISEASE RECURRENCE AFTER LOOP TREATMENT FOR HIGH GRADE CERVICAL INTRAEPITHELIAL
      NEOPLASIA: IGCS-0070 Cervical Cancer.

PMID- 25955911
TI  - CERVICAL CANCER AND PREGNANCY: THREE CASES DURING 2014 IN CARLOS VAN BUREN
      HOSPITAL, VALPARAISO-CHILE: IGCS-0072 Cervical Cancer.

PMID- 25955912
TI  - POSITIVE MARGINS IN COLD KNIFE CONE: PREVALENCE AND RESIDUAL LESIONS: IGCS-0073
      Cervical Cancer.

PMID- 25955913
TI  - LAPAROSCOPIC RADICAL TRACHELECTOMY: TECHNIQUE, FEASIBILITY AND OUTCOMES.
      EXPERIENCE HOSPITAL ITALIANO BUENOS AIRES, ARGENTINA: IGCS-0075 Cervical Cancer.

PMID- 25955914
TI  - VAGINAL RADICAL TRACHELECTOMY. A 10 YEARS EXPERIENCE OF 3 CENTERS IN CHILE: IGCS
      0076 Cervical Cancer.

PMID- 25955915
TI  - EVALUATION OF CONE DEPTH TO ACHIEVE NEGATIVE MARGINS AFTER ELECTROSURGICAL
      TREATMENT FOR HIGH GRADE CERVICAL INTRAEPITHELIAL NEOPLASIA: IGCS-0078 Cervical
      Cancer.

PMID- 25955916
TI  - LAPAROSCOPIC POSTERIOR EXENTERATION IN CERVICAL CANCER: INITIAL EXPERIENCE AT
      HOSPITAL ITALIANO DE BUENOS AIRES: IGCS-0085 Cervical Cancer.

PMID- 25955917
TI  - TREATMENT OUTCOMES OF PATIENTS WITH EARLY STAGE CERVICAL CANCER TREATED WITH
      LAPAROTOMY COMPARED TO ROBOTICALLY ASSISTED LAPAROSCOPIC APPROACH: IGCS-0089
      Cervical Cancer.

PMID- 25955918
TI  - LAPAROSCOPIC PARAAORTIC INFRARENAL LYMPHADENECTOMY: ANATOMICAL ANOMALIES FOUND IN
      OUR SERIES OF CASES AT THE GYNECOLOGIC ONCOLOGY SECTION, DEPARTMENT OF
      GYNECOLOGY, HOSPITAL ITALIANO DE BUENOS AIRES: IGCS-0090 Cervical Cancer.

PMID- 25955919
TI  - O&G RESIDENTS IN BRAZIL WOULD CONSIDER GYNECOLOGIC ONCOLOGY AS A SUBSPECIALTY IF
      IT WERE OFFICIALLY RECOGNIZED AND DON'T FEEL READY TO PERFORM RADICAL
      HYSTERECTOMIES: IGCS-0091 Cervical Cancer.

PMID- 25955920
TI  - CLINICAL ADVANTAGES OF NERVE-SPARING RADICAL HYSTERECTOMY OF CERVICAL CANCER:
      IGCS-0096 Cervical Cancer.

PMID- 25955921
TI  - DETECTION OF E6-E7 MRNA OF HIGH RISK HUMAN PAPILLOMAVIRUS IN NEGATIVE LYMPH NODES
      IN PATIENTS WITH CERVICAL CANCER: A POSSIBLE EARLY BIOMARKER OF SUBCLINICAL
      METASTASIS: IGCS-0104 Cervical Cancer.

PMID- 25955922
TI  - THE ABDOMINAL RADICAL TRACHELECTOMY SPARING THE UTERINE ARTERIES (A.R.T.- S.U.A)
      & THE PELVIC AUTONOMIC PLEXUS (P.P.A.P.) IN CERVICAL CANCER (CC): ONCOLOGICAL &
      FERTILITY OUTCOMES OF THIS NOVEL SURGICAL TECHNIQUE: IGCS-0105 Cervical Cancer.

PMID- 25955923
TI  - GESTATIONAL TROPHOBLASTIC DISEASE: INCREASE OF INCIDENCE IN CARLOS VAN BUREN
      HOSPITAL, VALPARAISO - CHILE: IGCS-0074 Gestational Trophoblastic Neoplasia.

PMID- 25955924
TI  - MOLECULAR CHARACTERIZATION OF GESTATIONAL TROPHOBLASTIC DISEASE: IGCS-0097
      Gestational Trophoblastic Neoplasia.

PMID- 25955926
TI  - LAPAROSCOPIC TREATMENT FOR ISOLATED PARA-AORTIC LYMPH NODE RECURRENCE: IGCS-0086
      Imaging / Staging.

PMID- 25955925
TI  - ROLE OF INDOCYANINE GREEN (ICG) IN SENTINEL NODE MAPPING IN GYNECOLOGIC CANCER: A
      TIME FOR A NEW STANDARD OF CARE?: IGCS-0083 Imaging / Staging.

PMID- 25955927
TI  - ASSESSMENT OF POSTOPERATIVE MORBIDITY RISK AFTER HYSTERECTOMY USING THE SURGICAL
      APGAR SCORE: IGCS-0041 05. Nursing, Symptom Management, Palliation.

PMID- 25955928
TI  - THE RELATIONSHIP BETWEEN SELF-EFFICACY AND ADHERENCE TO PAP TEST IN A GROUP OF
      CHILEAN WOMEN: IGCS-0051 Nursing, Symptom Management, Palliation.

PMID- 25955929
TI  - MOST QUALITY OF LIFE QUESTIONNAIRES USED IN PEER-REVIEWED CERVICAL CANCER
      SURVIVALS SURVEYS ARE NOT DISEASE-SPECIFIC INSTRUMENTS AND HAVE NOT BEEN
      PREVIOUSLY VALIDATED: IGCS-0094 Nursing, Symptom Management, Palliation.

PMID- 25955930
TI  - LIFETIME RISK OF OVARIAN CANCER BASED ON ENDOMETRIOSIS AND OTHER RISK FACTORS:
      IGCS-0014 06. Ovarian Cancer.

PMID- 25955931
TI  - DOES TALC EXPOSURE CAUSE OVARIAN CANCER?: IGCS-0015 Ovarian Cancer.

PMID- 25955932
TI  - SURGICAL STAGING OF OVARIAN CANCER (I FIGO STAGE): IGCS-0018 Ovarian Cancer.

PMID- 25955933
TI  - ADVANCED STAGE OF EPITHELIAL OVARIAN CANCER (II-IV FIGO STAGE). THE ROLE OF LYMPH
      NODE DISSECTION: IGCS-0019 Ovarian Cancer.

PMID- 25955934
TI  - NHE1 PROMOTE CELL PROLIFERATION IN OVARIAN CANCER: A ROLE OF HYPOXIA-INDUCIBLE
      FACTORS.: IGCS-0038 06. Ovarian Cancer.

PMID- 25955935
TI  - DIFFERENTIALLY EXPRESSED MIRNAS AND THEIR SURVIVAL PREDICTION IN THE HIGH GRADE
      SEROUS AND CLEAR CELL OVARIAN CARCINOMA: IGCS-0043 06. Ovarian Cancer.

PMID- 25955937
TI  - IFOSFAMIDUM AS PALLIATIVE TREATMENT FOR ADVANCED OVARIAN CANCER: IGCS-0063 06.
      Ovarian Cancer.

PMID- 25955936
TI  - FIBRIN SEALANT HEMOSTATIC PATCH CLINICAL EFFECTIVENESS EVALUATION IN ADVANCED
      OVARIAN CANCER PATIENTS UNDERWENT PELVIC LYMPHADENECTOMY: INSTITUTIONAL
      EXPERIENCE: IGCS-0062 06. Ovarian Cancer.

PMID- 25955938
TI  - CAN WE IMPROVE DETECTION OF BORDERLINE OVARIAN TUMORS?: IGCS-0065 Ovarian Cancer.

PMID- 25955939
TI  - BRAIN METASTASES FROM EPITHELIAL OVARIAN CANCER: CLINICOPATHOLOGICAL FINDINGS. A
      RETROSPECTIVE SINGLE INSTITUTION STUDY: IGCS-0067 06. Ovarian Cancer.

PMID- 25955940
TI  - CLINICAL MANAGEMENT OF BORDERLINE OVARIAN TUMORS IN DR SOTERO DEL RIO HOSPITAL:
      IGCS-0068 Ovarian Cancer.

PMID- 25955941
TI  - ADVANCED OVARIAN CANCER: A CHILEAN UNIVERSITY HOPITAL EXPERIENCE: IGCS-0077
      Ovarian Cancer.

PMID- 25955942
TI  - SEROUS PSAMMOCARCINOMA OF THE OVARY AND PERITONEUM: LONG TERM RECURRENCE: IGCS
      0080 Ovarian Cancer.

PMID- 25955943
TI  - LEPTIN PROMOTES A MORE AGGRESIVE BEHAVIOR OF OVARIAN CANCER CELLS: A POTENTIAL
      EXPLANATION FOR A WORSE PROGNOSIS IN OBESE OVARIAN CANCER PATIENTS: IGCS-0095
      Ovarian Cancer.

PMID- 25955944
TI  - MOLECULAR FINGERPRINTS OF MIXED ENDOMETRIOID AND SEROUS ADENOCARCINOMA OF THE
      ENDOMETRIUM: IGCS-0044 Uterine Cancer, including Sarcoma.

PMID- 25955945
TI  - UNDIFFERENTIATED ENDOMETRIAL CANCER, A DIFFERENT ENTITY WITH AN AGGRESSIVE
      BEHAVIOR: IGCS-0060 Uterine Cancer, including Sarcoma.

PMID- 25955946
TI  - EARLY STAGE ENDOMETRIAL CANCER: LAPAROSCOPY VS LAPAROTOMY: IGCS-0081 Uterine
      Cancer, including Sarcoma.

PMID- 25955947
TI  - TWO CASE OF ATYPICAL ENDOMETRIAL HYPERPLASIA ASSOCIATED WITH "BIOIDENTICAL"
      HORMONE REPLACEMENT THERAPY: IGCS-0084 Uterine Cancer, including Sarcoma.

PMID- 25955948
TI  - THE SIGNIFICANCE OF PRE-OPERATIVE ENDOMETRIAL SAMPLING IN GRADE 1, LOW RISK
      ENDOMETRIAL CANCERS: IGCS-0088 Uterine Cancer, including Sarcoma.

PMID- 25955949
TI  - ROBOTIC SURGERY INCREASES PATIENT's ACCESS TO MINIMALLY INVASIVE SURGERY FOR
      HYSTERECTOMIES: IGCS-0098 Uterine Cancer, including Sarcoma.

PMID- 25955950
TI  - LASER VAPORIZATION IN VULVAR INTRAEPITHELIAL NEOPLASIA (VIN), VAGINAL
      INTRAEPITHELIAL NEOPLASIA (VAIN) AND CONDYLOMATA ACUMINATA: IGCS-0093 Vulvar and
      Vaginal Cancer.

PMID- 25955951
TI  - PROGNOSTIC SIGNIFICANCE OF TUMOR SIZE IN SQUAMOUS CELL CARCINOMA OF THE VULVA:
      IGCS-0107 Vulvar and Vaginal Cancer.

PMID- 25955952
TI  - Determination of trace metal concentrations in ginseng (Panax Quinquefolius
      (American)) roots for forensic comparison using Inductively Coupled Plasma Mass
      Spectrometry.
AB  - The trace metal content of roots of samples of the American ginseng natural
      herbal plant species (Panax quinquefolius) was investigated as a means of
      differentiating between this species grown on Wisconsin and New Zealand farms,
      and from Canadian and Chinese sources. ICP-MS measurements were undertaken by
      ashing samples of the roots and then digestion with conc. HNO3 and H2O2. There
      was considerable variation in the concentrations of 28 detectable elements along
      the length of a root, between different roots, between different farms/sources
      and between different countries. Statistical processing of the log-transformed
      concentration data was undertaken using principal component analysis (PCA) and
      discriminant function analysis (DFA). Although PCA showed some differentiation
      between samples, a much clearer discrimination of the Panax quinquefolius species
      of ginseng from the four countries was observed using DFA. 88% of the variation
      between countries could be accounted for by only using discriminant function 1
      while 80% of the remaining 12% of the variation between countries is accounted
      for by discriminant function 2. The Fisher Classification Functions classify 98%
      of the 87 samples to the correct country of origin with 97% of the cross
      validated cases correctly classified. The predictive ability of this DFA model
      was further tested by constructing 100 discriminant models each using a random
      selection of the data for two thirds of the 87 sampled ginseng root tops, and
      then using the resulting classification functions to determine correctly the
      country of origin of the remaining third of the cases. The mean success rate of
      the 100 classifications was 92%. These results suggest that measurement and
      statistical analysis of just the trace metal content of the roots of Panax
      quinquefolius promises to be an excellent predictor of the country of origin of
      this ginseng species. 

PMID- 25955953
TI  - Implant Prosthetic Rehabilitation in Controlled HIV-Positive Patients: A
      Prospective Longitudinal Study with 1-Year Follow-Up.
AB  - PURPOSE: The clinical trial aimed to evaluate the survival of implant-prosthetic
      rehabilitation in controlled HIV-positive patients. MATERIALS AND METHODS: This
      mono-centric study included HIV patients with a stable disease, requiring implant
      rehabilitation, with good oral hygiene. Each patient received at least one dental
      implant. After 90 days in the upper jaw and 60 days in the lower jaw, the
      appropriate prosthesis was delivered.Primary outcome measures were prosthetic
      failures, implant failures, peri-implant marginal bone level changes (MBLCs), and
      biological complications (peri-implantitis, pus, pain, paresthesia). Data were
      recorded before the intervention (T0), and 6 (T1) and 12 months (T2) after.
      RESULTS: Implants were positioned in 68 patients (22 females and 46 males; 194
      implants). Two dropouts occurred for exacerbation of the disease before the sixth
      month of follow-up, and 66 patients (with 190 implants) completed the study.
      Forty-eight patients (70.6%) received total removable dentures; 11 patients
      (16.2%) received partial prosthesis, and nine patients (13.2%) received single
      elements.Implant failure occurred in nine patients (15 fixtures out of 190).
      These were early implant failures due to primary infection (five fixtures out of
      190: 2.6%) and to peri-implantitis (10 fixtures out of 190: 5.2%). Prosthetic
      failure was registered in two patients (3% of patients) due to the loss of all
      the fixtures. Pus and pain were observed in 4/7 and 3/7 patients with peri
      implantitis, respectively. No fractures of fixtures or paresthesia were
      registered. At T2, the mean peri-implant MBLC was -1.19 +/- 0.87 mm. CONCLUSIONS:
      Within its limitations, the study showed that in a well-controlled population of
      HIV patients implant rehabilitation can be a suitable options with results
      slightly worse to those obtained in normal population. A higher incidence of peri
      implant infections in the first six months was present pointing to the need of a
      proper protocol for infection control.

PMID- 25955954
TI  - Early diagnosis of osteopenia/osteoporosis by bone mineral density test using DXA
      method in early adulthood-a pre-emptive step towards future bone health.

PMID- 25955955
TI  - Correction: Combined photothermal and photodynamic therapy delivered by PEGylated
      MoS2 nanosheets.

PMID- 25955956
TI  - A pharmacological and phytochemical overview on Satureja.
AB  - CONTEXT: Satureja (Lamiaceae) species are used as flavoring compounds in food,
      pharmaceutical, and cosmetic industries because of its sweetness and simple
      cultivation characteristics. They have traditionally been used as muscle pain
      relievers, tonic, and carminative agents to treat stomach and intestinal
      disorders such as cramps, nausea, indigestion, and diarrhea, due to their
      considerable phytochemical characteristics. OBJECTIVE: This review evaluates some
      information published since 1989 on Satureja genus from a systematic perspective
      in terms of its pharmacological and phytochemical characteristics. MATERIALS AND
      METHODS: Web of Science, PubMed, Scopus, and Google Scholar databases were
      searched up to March 2014. "Satureja" was used as a research term without
      narrowing or limiting research elements. After obtaining all reports from
      database (a total number is about 637), the papers were carefully analyzed in
      order to find data related to the topic of this review. RESULTS: In this review,
      453 reports were used which were published between 1989 and 2014. The study was
      compiled into two sections (Pharmacology and Phytochemistry). In the pharmacology
      section, more than 50 different activities were studied. In the second section,
      in addition to other compounds and inorganic substances, volatiles, phenolic
      acids, and flavonoids were discussed. DISCUSSION AND CONCLUSION: According to our
      contemporary information, Satureja species have been evaluated for their wide
      range of biological activities. However, a small part of these studies have been
      carried out on the active principles. Therefore, in the future, more studies
      should be carried out to identify responsible phytochemicals for the various
      activities.

PMID- 25955957
TI  - Olive oil and its phenolic compounds (hydroxytyrosol and tyrosol) ameliorated
      TCDD-induced heptotoxicity in rats via inhibition of oxidative stress and
      apoptosis.
AB  - CONTEXT: Naturally occurring polyphenols including olive oil (OO) and its
      constituents hydroxytyrosol (HT) and tyrosol (TY), consumed in the Mediterranean
      diet, have shown to treat various ailments due to their remarkable antioxidant
      properties. OBJECTIVE: The present study investigates the hepatoprotective
      effects of OO and its phenolic compounds HT and TY against TCDD-induced
      hepatotoxicity in male Wistar rats. MATERIALS AND METHODS: TCDD was administered
      at a dose of 100 ng/kg p.o. for 20 d. Administration of OO (10 ml/kg; oral), HT
      (0.5 mg/kg; oral), and TY (30 mg/kg; i.p) was started 5 d prior to TCDD
      administration, and continued for 25 d with or without TCDD administration. At
      the end of the experiment (25 d), blood was taken for biochemical analyses and
      liver for the measurement of macromolecular damages, antioxidant status,
      expressions of CYP1A1, and apoptotic factors. RESULTS: TCDD administration
      resulted in significant (p < 0.05) increase in the level of hepatic stress
      markers ALT (101.6 +/- 3.07 IU/l), AST (295.0 +/- 3.0 IU/l), and ALP (266.66 +/-
      3.7 IU/l). Also, biochemical analyses of liver reported elevation in nitrite and
      protein carbonyl content and depletion of NQO1 and HO. However, OO, HT, and TY
      restored the antioxidant status. Protein expressions by Western Blot technique
      showed an increase in the level of CYP1A1 and Bax and a decreased level of Bcl-2
      on TCDD treatment, and vice versa on OO, HT, and TY treatment. DISCUSSION AND
      CONCLUSION: Our work concludes that dietary supplementation of OO, HT, and TY
      could serve as a potential preventive drug for TCDD-induced hepatotoxicity.

PMID- 25955959
TI  - A comparative study of disinfection efficiency and regrowth control of
      microorganism in secondary wastewater effluent using UV, ozone, and ionizing
      irradiation process.
AB  - Ionizing radiation technology was suggested as an alternative method to
      disinfection processes, such as chlorine, UV, and ozone. Although many studies
      have demonstrated the effectiveness of irradiation technology for microbial
      disinfection, there has been a lack of information on comparison studies of
      disinfection techniques and a regrowth of each treatment. In the present study,
      an ionizing radiation was investigated to inactivate microorganisms and to
      determine the critical dose to prevent the regrowth. As a result, it was observed
      that the disinfection efficiency using ionizing radiation was not affected by the
      seasonal changes of wastewater characteristics, such as temperature and
      turbidity. In terms of bacterial regrowth after disinfection, the ionizing
      radiation showed a significant resistance of regrowth, whereas, on-site UV
      treatment is influenced by the suspended solid, temperature, or precipitation.
      The electric power consumption was also compared for the economic feasibility of
      each technique at a given value of disinfection efficiency of 90% (1-log),
      showing 0.12, 36.80, and 96.53 Wh/(L/day) for ionizing radiation, ozone, and UV,
      respectively. The ionizing radiation requires two or three orders of magnitude
      lower power consumption than UV and ozone. Consequently, ionizing radiation can
      be applied as an effective and economical alternative technique to other
      conventional disinfection processes.

PMID- 25955960
TI  - Platinum carbon bond formation via Cu(I) catalyzed Stille-type transmetallation:
      reaction scope and spectroscopic study of platinum-arylene complexes.
AB  - The preparation of Pt(ii) complexes of the type trans-L2Pt(Ar)Cl, L2Pt(Ar)2, and
      L2Pt(Ar)(Ar') (L = PBu3, Ar = arylene) by CuI catalyzed reaction of cis
      (PBu3)2PtCl2 with aryl-stannanes is reported. The reactions proceed at 25-60 
      degrees C in moderate to good yields. The reaction is demonstrated to occur with
      phenyl- and 2-thienyl-stannanes that include a variety of functionality, and all
      of the resulting Pt-aryl complexes were fully characterized by (1)H, (13)C, and
      (31)PNMR spectroscopy, as well as mass spectroscopy. Photophysical properties of
      the L2Pt(Ar)2, and L2Pt(Ar)(Ar') complexes were measured, including steady-state
      absorption, photoluminescence, and photoluminescence quantum yields, in order to
      understand how attachment of the platinum metal influences the excited state
      properties of the arylene ligands. This work affirms that CuI catalyzed coupling
      between Ar-SnR3 and L2PtCl2 is a useful platinum-carbon bond formation reaction. 

PMID- 25955961
TI  - The International Hypoxia Symposium 2015 in Lake Louise: A Report.

PMID- 25955958
TI  - Dual targeting of TNF-alpha and free radical toxic stress as a promising strategy
      to manage experimental polycystic ovary.
AB  - CONTEXT: It is now clear that oxidative stress (OS) and chronic low-grade
      inflammation are two main pathways involved in polycystic ovary syndrome (PCOS)
      pathogenesis. Therefore, simultaneous targeting of these pathways by means of
      carvedilol and Semelil (ANGIPARSTM), as established medicines with dual anti
      cytokine and anti-oxidant potential may be a therapeutic alternative approach to
      the current treatments. OBJECTIVE: The objective of this study is to study the
      protective effects of carvedilol and ANGIPARSTM on inflammatory and oxidative
      response in hyperandrogenism-induced polycystic ovary (PCO). MATERIALS AND
      METHODS: The murine model of PCO was induced by letrozole (1 mg/kg/d; orally) and
      effective doses of carvedilol (10 mg/kg/d; orally) and ANGIPARSTM (2.1 mg/kg/d;
      orally) were administrated for 21 d in PCO and non-PCO healthy rats. Ovarian
      folliculogenesis, sex hormones concentrations, OS, inflammatory, and metabolic
      biomarkers were assessed in serum and ovaries. RESULTS: PCO rats exhibited
      ovarian cystogenesis which was preserved by the application of carvedilol and
      ANGIPARSTM. In comparison with controls, decreased level of the total antioxidant
      power (TAP) and higher levels of reactive oxygen species (ROS) and lipid
      peroxidation (LPO) in serum and ovaries (2.41 +/- 0.67 versus 0.72 +/- 0.11; and
      0.17 +/- 0.04 versus 0.05 +/- 0.01; 5.48 +/- 1.30 versus 10.56 +/- 0.77; and 7.06
      +/- 1.94 versus 17.98 +/- 0.98; p < 0.05, respectively) were detected in PCO
      rats. Moreover, the PCO rats exhibited hyperandrogenism due to a 3.7-fold
      increase in serum testosterone concentration (35.04 +/- 3.17 versus 131.09 +/-
      13.24; p < 0.05) along with a 2.98-fold decrease in serum progesterone (6.19 +/-
      0.40 versus 18.50 +/- 1.03; p < 0.05) and 5.2-fold decrease in serum estradiol
      (9.30 +/- 0.61 versus 48.3 +/- 2.10; p < 0.05) when compared with those of the
      control group. However, similar to the control group, normal levels of OS markers
      and sex hormones were detected in ANGIPARSTM and carvedilol co-treated PCO rats.
      Besides, when compared with controls, increased levels of TNF-alpha (770.75 +/-
      42.06 versus 477.14 +/- 28.77; p < 0.05) and insulin (1.27 +/- 0.10 versus 0.36
      +/- 0.05; p < 0.05) in PCO rats were significantly inhibited by carvedilol and
      ANGIPARSTM co-treatment. DISCUSSION AND CONCLUSION: We evidenced the beneficial
      effects of carvedilol and ANGIPARSTM in PCO, which underpin the new alternative
      approach in using these kinds of medicines in female reproductive disorders.

PMID- 25955962
TI  - Trajectories of marijuana use from adolescence to adulthood predicting
      unemployment in the mid 30s.
AB  - BACKGROUND AND OBJECTIVES: Unemployment (5.5% as of 2015) is a serious social and
      economic problem in our society. Since marijuana use is an important factor
      related to unemployment, identifying the trajectory of the use of marijuana may
      aid intervention programs and research on unemployment. METHODS: Six hundred
      seventy-four participants (53% African-Americans, 47% Puerto Ricans) were
      surveyed (60% females) from ages 14 to 36. The first data collection was held
      when the participants were students attending schools in the East Harlem area of
      New York City. RESULTS: We found that the chronic marijuana use (OR = 4.07, p <
      .001; AOR = 2.58, p < .05) and the late marijuana quitter (OR = 2.91, p < .05)
      trajectory groups were associated with an increased likelihood of unemployment
      compared with the no marijuana use trajectory group. CONCLUSIONS AND SCIENTIFIC
      SIGNIFICANCE: The results suggest that those who use marijuana chronically are at
      greater risk for being unemployed. Consequently, these individuals should have
      access to and participate in marijuana cessation treatment programs in order to
      reduce their risk of unemployment. Unemployment intervention programs should also
      consider focusing on the cessation of the use of marijuana to decrease the
      likelihood of later unemployment.

PMID- 25955963
TI  - Pressure pain thresholds assessed over temporalis, masseter, and frontalis
      muscles in healthy individuals, patients with tension-type headache, and those
      with migraine--a systematic review.
AB  - A systematic review was conducted to identify and summarize the available
      scientific literature addressing pressure pain threshold (PPT) values over the
      temporalis, masseter, and frontalis muscles in healthy humans, patients with
      tension-type headache (TTH), and those with migraine both in males and females.
      Six relevant medical databases for the literature search were included: PubMed,
      Web of Science, Cochrane, CINAHL, BioMed Central, and Embase. The search strategy
      was performed applying 15 keywords (eg, pressure pain threshold, temporalis
      muscle, tension type headache, pressure algometer) and their combinations. A
      total of 156 articles were identified, and 40 relevant articles were included.
      The main outcomes of the systematic review were extracted, and it was
      demonstrated that the PPT values in general were lower in patients compared with
      healthy subjects, and this was especially noted for temporalis in both females
      (migraine: 231.2 +/- 38.3 kPa < TTH: 248.4 +/- 39.3 kPa < healthy: 282.1 +/- 70.8
      kPa) and males (migraine: 225.5 +/- 61.2 kPa < TTH: 264.2 +/- 32.5 kPa < healthy:
      314.8 +/- 63.3 kPa). The masseter muscle seemed to be more sensitive than the
      other 2 muscles, in both females (healthy: masseter 194.1 +/- 62.7 kPa <
      frontalis 277.5 +/- 51.1 kPa < temporalis 282.1 +/- 70.8 kPa) and males (healthy:
      masseter 248.2 +/- 48.4 kPa < temporalis 314.8 +/- 63.3 < frontalis 388 kPa).
      Females had lower PPT values than those of males in temporalis, masseter, and
      frontalis muscles. This work is the first to systematically review the scientific
      literature addressing PPT values over craniofacial muscles of healthy subjects,
      patients with TTH, and those with migraine to provide the PPT value ranges. Based
      on these findings, a set of guidelines was established to assist future studies
      including PPT assessments over craniofacial muscles. 

PMID- 25955964
TI  - Behavioral and neurochemical analysis of ongoing bone cancer pain in rats.
AB  - Cancer-induced bone pain is described as dull, aching ongoing pain. Ongoing bone
      cancer pain was characterized after intratibial injection of breast cancer cells
      in rats. Cancer produced time-dependent bone remodeling and tactile
      hypersensitivity but no spontaneous flinching. Conditioned place preference (CPP)
      and enhanced dopamine (DA) release in the nucleus accumbens (NAc) shell was
      observed after peripheral nerve block (PNB) selectively in tumor-bearing rats
      revealing nociceptive-driven ongoing pain. Oral diclofenac reversed tumor-induced
      tactile hypersensitivity but did not block PNB-induced CPP or NAc DA release.
      Tumor-induced tactile hypersensitivity, and PNB-induced CPP and NAc DA release,
      was blocked by prior subcutaneous implantation of a morphine pellet. In sham
      rats, morphine produced a modest but sustained increase in NAc DA release. In
      contrast, morphine produced a transient 5-fold higher NAc DA release in tumor
      bearing rats compared with sham morphine rats. The possibility that this
      increased NAc DA release reflected the reward of pain relief was tested by
      irreversible blockade of rostral anterior cingulate cortex (rACC) MU-opioid
      receptors (MORs). The rACC MOR blockade prevented the morphine-induced transient
      increased NAc DA release in tumor bearing rats but did not affect morphine
      induced effects in sham-operated animals. Consistent with clinical experience,
      ongoing cancer pain was controlled by morphine but not by a dose of diclofenac
      that reversed evoked hypersensitivity. Additionally, the intrinsic reward of
      morphine can be dissociated from the reward of relief of cancer pain by blockade
      of rACC MOR. This approach allows mechanistic and therapeutic assessment of
      ongoing cancer pain with likely translation relevance. 

PMID- 25955965
TI  - Predictors of the placebo analgesia response in randomized controlled trials of
      chronic pain: a meta-analysis of the individual data from nine industrially
      sponsored trials.
AB  - A large number of analgesics have failed to prove superiority over placebo in
      randomized controlled trials (RCTs), and as this has been related to increasing
      placebo responses, there is currently an interest in specifying predictors of the
      placebo response. The literature on placebo mechanisms suggests that factors
      related to patients' expectations of treatment efficacy are pivotal for the
      placebo response. Also, general characteristics of RCTs have been suggested to
      influence the placebo response. Yet, only few meta-analyses have directly tested
      these hypotheses. Placebo data from 9 industrially sponsored, randomized, double
      blind, placebo-controlled, multicenter phase III trials in 2017 adult patients
      suffering from chronic painful osteoarthritis (hip or knee) or low back pain were
      included. The primary outcome was pain intensity. Based on previous studies, we
      chose 3 expectancy-related primary predictors: type of active medication,
      randomization ratio, and number of planned face-to-face visits. In addition,
      explorative analyses tested whether RCT and patients' characteristics predicted
      the placebo response. Opioid trials, a high number of planned face-to-face
      visits, and randomization ratio predicted the magnitude of the placebo response,
      thereby supporting the expectancy hypothesis. Exploratory models with baseline
      pain intensity, age, washout length, and discontinuation because of adverse
      events accounted for approximately 10% of the variability in the placebo
      response. Based on these results and previous mechanisms studies, we think that
      patients' perception of treatment allocation and expectations toward treatment
      efficacy could potently predict outcomes of RCTs. 

PMID- 25955966
TI  - Dosage compensation can buffer copy-number variation in wild yeast.
AB  - Aneuploidy is linked to myriad diseases but also facilitates organismal
      evolution. It remains unclear how cells overcome the deleterious effects of
      aneuploidy until new phenotypes evolve. Although laboratory strains are extremely
      sensitive to aneuploidy, we show here that aneuploidy is common in wild yeast
      isolates, which show lower-than-expected expression at many amplified genes. We
      generated diploid strain panels in which cells carried two, three, or four copies
      of the affected chromosomes, to show that gene-dosage compensation functions at
      >30% of amplified genes. Genes subject to dosage compensation are under higher
      expression constraint in wild populations-but they show elevated rates of gene
      amplification, suggesting that copy-number variation is buffered at these genes.
      We find that aneuploidy provides a clear ecological advantage to oak strain
      YPS1009, by amplifying a causal gene that escapes dosage compensation. Our work
      presents a model in which dosage compensation buffers gene amplification through
      aneuploidy to provide a natural, but likely transient, route to rapid phenotypic
      evolution. 

PMID- 25955967
TI  - Local chromatin environment of a Polycomb target gene instructs its own
      epigenetic inheritance.
AB  - Inheritance of gene expression states is fundamental for cells to 'remember' past
      events, such as environmental or developmental cues. The conserved Polycomb
      Repressive Complex 2 (PRC2) maintains epigenetic repression of many genes in
      animals and plants and modifies chromatin at its targets. Histones modified by
      PRC2 can be inherited through cell division. However, it remains unclear whether
      this inheritance can direct long-term memory of individual gene expression states
      (cis memory) or instead if local chromatin states are dictated by the
      concentrations of diffusible factors (trans memory). By monitoring the expression
      of two copies of the Arabidopsis Polycomb target gene FLOWERING LOCUS C (FLC) in
      the same plants, we show that one copy can be repressed while the other is
      active. Furthermore, this 'mixed' expression state is inherited through many cell
      divisions as plants develop. These data demonstrate that epigenetic memory of FLC
      expression is stored not in trans but in cis. 

PMID- 25955968
TI  - Malaria-associated atypical memory B cells exhibit markedly reduced B cell
      receptor signaling and effector function.
AB  - Protective antibodies in Plasmodium falciparum malaria are only acquired after
      years of repeated infections. Chronic malaria exposure is associated with a large
      increase in atypical memory B cells (MBCs) that resemble B cells expanded in a
      variety of persistent viral infections. Understanding the function of atypical
      MBCs and their relationship to classical MBCs will be critical to developing
      effective vaccines for malaria and other chronic infections. We show that VH gene
      repertoires and somatic hypermutation rates of atypical and classical MBCs are
      indistinguishable indicating a common developmental history. Atypical MBCs
      express an array of inhibitory receptors and B cell receptor (BCR) signaling is
      stunted in atypical MBCs resulting in impaired B cell responses including
      proliferation, cytokine production and antibody secretion. Thus, in response to
      chronic malaria exposure, atypical MBCs appear to differentiate from classical
      MBCs becoming refractory to BCR-mediated activation and potentially interfering
      with the acquisition of malaria immunity. 

PMID- 25955969
TI  - Low cost, high performance processing of single particle cryo-electron microscopy
      data in the cloud.
AB  - The advent of a new generation of electron microscopes and direct electron
      detectors has realized the potential of single particle cryo-electron microscopy
      (cryo-EM) as a technique to generate high-resolution structures. Calculating
      these structures requires high performance computing clusters, a resource that
      may be limiting to many likely cryo-EM users. To address this limitation and
      facilitate the spread of cryo-EM, we developed a publicly available 'off-the
      shelf' computing environment on Amazon's elastic cloud computing infrastructure.
      This environment provides users with single particle cryo-EM software packages
      and the ability to create computing clusters with 16-480+ CPUs. We tested our
      computing environment using a publicly available 80S yeast ribosome dataset and
      estimate that laboratories could determine high-resolution cryo-EM structures for
      $50 to $1500 per structure within a timeframe comparable to local clusters. Our
      analysis shows that Amazon's cloud computing environment may offer a viable
      computing environment for cryo-EM. 

PMID- 25955971
TI  - BRET evidence that beta2 adrenergic receptors do not oligomerize in cells.
AB  - Bioluminescence resonance energy transfer (BRET) is often used to study
      association of membrane proteins, and in particular oligomerization of G protein
      coupled receptors (GPCRs). Oligomerization of class A GPCRs is controversial, in
      part because the methods used to study this question are not completely
      understood. Here we reconsider oligomerization of the class A beta2 adrenergic
      receptor (beta2AR), and reevaluate BRET titration as a method to study membrane
      protein association. Using inducible expression of the energy acceptor at
      multiple levels of donor expression we find that BRET between beta2AR protomers
      is directly proportional to the density of the acceptor up to ~3,000 acceptors
      MUm(-2), and does not depend on the density of the donor or on the acceptor:donor
      (A:D) stoichiometry. In contrast, BRET between tightly-associating control
      proteins does not depend on the density of the acceptor, but does depend on the
      density of the donor and on the A:D ratio. We also find that the standard
      frameworks used to interpret BRET titration experiments rely on simplifying
      assumptions that are frequently invalid. These results suggest that beta2ARs do
      not oligomerize in cells, and demonstrate a reliable method of assessing membrane
      protein association with BRET. 

PMID- 25955970
TI  - Maturation of a central brain flight circuit in Drosophila requires Fz2/Ca2+
      signaling.
AB  - The final identity of a differentiated neuron is determined by multiple signaling
      events, including activity dependent calcium transients. Non-canonical Frizzled2
      (Fz2) signaling generates calcium transients that determine neuronal polarity,
      neuronal migration, and synapse assembly in the developing vertebrate brain.
      Here, we demonstrate a requirement for Fz2/Ca(2+) signaling in determining the
      final differentiated state of a set of central brain dopaminergic neurons in
      Drosophila, referred to as the protocerebral anterior medial (PAM) cluster.
      Knockdown or inhibition of Fz2/Ca(2+) signaling during maturation of the flight
      circuit in pupae reduces Tyrosine Hydroxylase (TH) expression in the PAM neurons
      and affects maintenance of flight. Thus, we demonstrate that Fz2/Ca(2+)
      transients during development serve as a pre-requisite for normal adult behavior.
      Our results support a neural mechanism where PAM neuron send projections to the
      alpha' and beta' lobes of a higher brain centre, the mushroom body, and function
      in dopaminergic re-inforcement of flight. 

PMID- 25955973
TI  - Correction: Facile synthesis of mesoporous spinel NiCo2O4 nanostructures as
      highly efficient electrocatalysts for urea electro-oxidation.

PMID- 25955974
TI  - Green and blue emitting 3D structured Tb:Ce2(WO4)3 and Tb:Ce10W22O81
      micromaterials.
AB  - In this paper, various microstructures of Ce2(WO4)3 and Ce10W22O81 were prepared
      by applying a hydrothermal synthesis, in a ligand-free environment, and in the
      presence of a dioctyl sodium sulfosuccinate (DSS) surfactant, after which the
      materials were heat treated at a temperature of 900  degrees C. Depending on the
      ratio of cerium ions to sodium tungstate, as well as the reaction pH, two
      different cerium tungstate materials were obtained. The source of cerium, and the
      presence or absence of the surfactant had a significant influence on the
      morphology of the final product. The photoluminescence properties of Tb(3+) doped
      cerium tungstate materials were investigated. Luminescence measurements showed an
      efficient charge transfer from the tungstate groups to the Tb(3+) ions. All the
      materials emitted blue or green light under UV excitation. 

PMID- 25955972
TI  - History of high-risk HPV and Pap test results in a large cohort of patients with
      invasive cervical carcinoma: experience from the largest women's hospital in
      China.
AB  - BACKGROUND: Current cervical cancer screening guidelines recommend screening with
      a Papanicolaou (Pap) test or by cotesting (Pap and human papillomavirus [HPV]).
      Given the importance of high-risk HPV (hrHPV) infection in the development of
      cervical cancer, some studies are now suggesting the use of primary hrHPV testing
      as a possible screening modality. To gain further insight into the role of both
      Pap testing and hrHPV testing, the authors examined prior screening results in a
      population of Chinese patients with invasive cervical carcinoma. METHODS: Cases
      with a histologic diagnosis of invasive cervical carcinoma were retrieved from
      the Obstetrics and Gynecology Hospital of Fudan University from January 2011 to
      October 2014. Prior hrHPV testing and Pap test results within 3 years before the
      cancer diagnosis were recorded. RESULTS: Of 3714 patients with invasive cervical
      carcinoma, over a 46-month period, 525 had prior hrHPV testing using Hybrid
      Capture 2 within 3 years and 238 patients had Pap cytology testing within 1 year
      before the histological diagnosis. Within the 1-year period before diagnosis, the
      overall hrHPV-negative rate was 15.5% (74 of 477 patients) and the Pap-negative
      rate was also 15.5% (37 of 238 patients). Only 9 of 231 patients with both hrHPV
      testing and Pap testing (3.9%) had a double-negative result. Compared with
      squamous cell carcinoma, adenocarcinoma has significantly higher rates of prior
      negative results with both hrHPV and Pap cytology. CONCLUSIONS: The results of
      the current study demonstrated prior results of hrHPV testing and Pap cytology in
      a population of women in China who had not undergone intensive prior screening.
      Both hrHPV testing and Pap cytology were found to have similar negative rates in
      this population and, not surprisingly, there were fewer women who had negative
      testing results using both testing modalities.

PMID- 25955975
TI  - Her life ended jumping from the fifth floor: the importance of scene
      investigation and the need for restrictive means to prevent jumping suicide.
AB  - In January 2014, a dead woman was found lying near the back entrance of a
      building belonging to Bari University Hospital compound. After the external
      examination and identification of the corpse, through history, circumstances, and
      postmortem findings, it was supposed that the woman probably committed suicide,
      by jumping from the nearby building. But only after additional investigation of
      the scene was it possible to locate the window through which the victim had
      jumped, by assessing the height from which she leapt. We underline the importance
      of the examination of the scene. It has to be done with circumspection, even in
      cases that could be considered routine, paying attention to details, not
      excluding things that, at first glance, seem to be unnecessary. Inspection needs
      time, patience and accuracy, knowledge, competence, and intuition and must be the
      result of an efficient team action. Furthermore the occurrence of suicides,
      particularly jumping from a height, among immediate postdischarge psychiatric
      patients, stresses the importance of immediate follow-up treatment and
      alternative preventive strategies, considering, of course, the feasibility of
      structural means. 

PMID- 25955976
TI  - Deadly portal was caught red-handed: the computed tomographic images of the
      source of pulmonary air embolism.

PMID- 25955977
TI  - Screen-Printable and Flexible RuO2 Nanoparticle-Decorated PEDOT:PSS/Graphene
      Nanocomposite with Enhanced Electrical and Electrochemical Performances for High
      Capacity Supercapacitor.
AB  - This work describes a ternary screen-printed electrode system, composed of
      aqueous poly(3,4-ethylenedioxythiophene):poly(4-styrenesulfonic acid) ( PEDOT:
      PSS), graphene, and hydrous ruthenium(IV) oxide (RuO2) nanoparticles for use in
      high-performance electrochemical capacitors. As a polymeric binder, PSS allows
      stable dispersion of graphene and hydrous RuO2 nanoparticles (NPs) in an aqueous
      PEDOT: PSS system through electrostatic stabilization, ensuring better
      utilization of the three components. Additional PSS molecules were added to
      optimize the solution viscosity to obtain screen-printed electrodes. The effects
      of graphene and hydrous RuO2 NPs on the electrical and electrochemical properties
      of PEDOT: PSS were systematically investigated. The graphene sheets greatly
      enhanced the charge-transport properties, such as the doping level and
      conjugation length, through strong pi-pi stacking interactions with the PEDOT
      structure. The hydrous RuO2 NPs anchored to the PEDOT: PSS/graphene surfaces
      facilitated redox reactions with the surrounding electrolyte, and significantly
      enhanced the specific capacitance of the electrode materials. The resulting
      RuO2/PEDOT:PSS/graphene electrode with a thickness of ~5 MUm exhibited high
      conductivity (1570 S cm(-1)), a large specific capacitance (820 F g(-1)), and
      good cycling stability (81.5% after 1000 cycles).

PMID- 25955979
TI  - Quantification of strain induced damage in medial collateral ligaments.
AB  - In the past years, there have been several experimental studies that aimed at
      quantifying the material properties of articular ligaments such as tangent
      modulus, tensile strength, and ultimate strain. Little has been done to describe
      their response to mechanical stimuli that lead to damage. The purpose of this
      experimental study was to characterize strain-induced damage in medial collateral
      ligaments (MCLs). Displacement-controlled tensile tests were performed on 30 MCLs
      harvested from Sprague Dawley rats. Each ligament was monotonically pulled to
      several increasing levels of displacement until complete failure occurred. The
      stress-strain data collected from the mechanical tests were analyzed to determine
      the onset of damage and its evolution. Unrecoverable changes such as increase in
      ligament's elongation at preload and decrease in the tangent modulus of the
      linear region of the stress-strain curves indicated the occurrence of damage.
      Interestingly, these changes were found to appear at two significantly different
      threshold strains (P<0.05). The mean threshold strain that determined the
      increase in ligament's elongation at preload was found to be 2.84% (standard
      deviation (SD) = 1.29%) and the mean threshold strain that caused the decrease in
      the tangent modulus of the linear region was computed to be 5.51% (SD = 2.10%),
      respectively. The findings of this study suggest that the damage mechanisms
      associated with the increase in ligament's elongation at preload and decrease in
      the tangent modulus of the linear region in the stress-strain curves in MCLs are
      likely different. 

PMID- 25955980
TI  - Effect of 1.5% Topical Diclofenac on Clinical Neuropathic Pain.
AB  - BACKGROUND: Neuropathic pain is a condition resulting from injury to the
      peripheral and/or central nervous system. Despite extensive research over the
      last several decades, neuropathic pain remains difficult to manage. METHODS: The
      authors conducted a randomized, placebo-controlled, double-blinded, and crossover
      clinical trial to examine the effect of 1.5% topical diclofenac (TD) on
      neuropathic pain. The authors hypothesized that 1.5% TD would reduce the visual
      pain score and improve both quantitative sensory testing and functional status in
      subjects with neuropathic pain. The authors recruited subjects with postherpetic
      neuralgia and complex regional pain syndrome. The primary outcome was subject's
      visual pain score. RESULTS: Twenty-eight subjects completed the study (12 male
      and 16 female) with the mean age of 48.8 yr. After 2 weeks of topical
      application, subjects in 1.5% TD group showed lower overall visual pain score
      compared with placebo group (4.9 [1.9] vs. 5.6 [2.1], difference: 0.8; 95% CI,
      0.1 to 1.3; P = 0.04) as well as decreased burning pain (2.9 [2.6] vs. 4.3 [2.8],
      difference, 1.4; 95% CI, 0.2 to 2.6; P = 0.01). There were no statistical
      differences in constant pain, shooting pain, or hypersensitivity over the painful
      area between the groups. This self-reported improvement of pain was corroborated
      by the decreased pain summation detected by quantitative sensory testing. There
      were no statistically significant changes in functional status in these subjects.
      There were no complications in both groups. CONCLUSION: The findings indicate
      that 1.5% TD may serve as an effective treatment option for patients with
      neuropathic pain from postherpetic neuralgia and complex regional pain syndrome.

PMID- 25955978
TI  - Selectivity Mechanism of the Voltage-gated Proton Channel, HV1.
AB  - Voltage-gated proton channels, HV1, trigger bioluminescence in dinoflagellates,
      enable calcification in coccolithophores, and play multifarious roles in human
      health. Because the proton concentration is minuscule, exquisite selectivity for
      protons over other ions is critical to HV1 function. The selectivity of the open
      HV1 channel requires an aspartate near an arginine in the selectivity filter
      (SF), a narrow region that dictates proton selectivity, but the mechanism of
      proton selectivity is unknown. Here we use a reduced quantum model to elucidate
      how the Asp-Arg SF selects protons but excludes other ions. Attached to a ring
      scaffold, the Asp and Arg side chains formed bidentate hydrogen bonds that
      occlude the pore. Introducing H3O(+) protonated the SF, breaking the Asp-Arg
      linkage and opening the conduction pathway, whereas Na(+) or Cl(-) was trapped by
      the SF residue of opposite charge, leaving the linkage intact, thus preventing
      permeation. An Asp-Lys SF behaved like the Asp-Arg one and was experimentally
      verified to be proton-selective, as predicted. Hence, interacting acidic and
      basic residues form favorable AspH(0)-H2O(0)-Arg(+) interactions with hydronium
      but unfavorable Asp(-)-X(-)/X(+)-Arg(+) interactions with anions/cations. This
      proposed mechanism may apply to other proton-selective molecules engaged in
      bioenergetics, homeostasis, and signaling. 

PMID- 25955981
TI  - Propensity Score-matched Comparison of Postoperative Adverse Outcomes between
      Geriatric Patients Given a General or a Neuraxial Anesthetic for Hip Surgery: A
      Population-based Study.
AB  - BACKGROUND: The effects of the mode of anesthesia on major adverse postoperative
      outcomes in geriatric patients are still inconclusive. The authors hypothesized
      that a neuraxial anesthetic (NA) rather than a general anesthetic (GA) would
      yield better in-hospital postoperative outcomes for geriatric patients undergoing
      hip surgery. METHODS: The authors used data from Taiwan's 1997-2011 in-patient
      claims database to evaluate the effect of anesthesia on in-hospital outcomes. The
      endpoints were mortality, stroke, transient ischemic stroke, myocardial
      infarction, respiratory failure, and renal failure. Of the 182,307 geriatric
      patients who had hip surgery, a GA was given to 53,425 (29.30%) and an NA to
      128,882 (70.70%). To adjust for baseline differences and selection bias, patients
      were matched on propensity scores, which left 52,044 GA and 52,044 NA patients.
      RESULTS: GA-group patients had a greater percentage and higher odds of adverse in
      hospital outcomes than did NA-group patients: death (2.62 vs. 2.13%; odds ratio
      [OR], 1.24; 95% CI, 1.15 to 1.35; P < 0.001), stroke (1.61 vs. 1.38%; OR, 1.18,
      95% CI, 1.07 to 1.31; P = 0.001), respiratory failure (1.67 vs. 0.63%; OR, 2.71;
      95% CI, 2.38 to 3.01; P < 0.001), and intensive care unit admission (11.03 vs.
      6.16%; OR, 1.95; 95% CI, 1.87 to 2.05; P < 0.001), analyzed using conditional
      logistic regression. Moreover, patients given a GA had longer hospital stays
      (10.77 +/- 8.23 vs. 10.44 +/- 6.67 days; 95% CI, 0.22 to 0.40; P < 0.001) and
      higher costs (New Taiwan Dollars [NT$] 86,606 +/- NT$74,162 vs. NT$74,494 +/-
      NT$45,264; 95% CI, 11,366 to 12,859; P < 0.001). CONCLUSION: For geriatric
      patients undergoing hip surgery, NA was associated with fewer odds of adverse
      outcomes than GA.

PMID- 25955982
TI  - Critical Changes in Cortical Neuronal Interactions in Anesthetized and Awake
      Rats.
AB  - BACKGROUND: Neuronal interactions are fundamental for information processing,
      cognition, and consciousness. Anesthetics reduce spontaneous cortical activity;
      however, neuronal reactivity to sensory stimuli is often preserved or augmented.
      How sensory stimulus-related neuronal interactions change under anesthesia has
      not been elucidated. In this study, the authors investigated the visual stimulus
      related cortical neuronal interactions during stepwise emergence from desflurane
      anesthesia. METHODS: Parallel spike trains were recorded with 64-contact
      extracellular microelectrode arrays from the primary visual cortex of chronically
      instrumented, unrestrained rats (N = 6) at 8, 6, 4, and 2% desflurane anesthesia
      and wakefulness. Light flashes were delivered to the retina by transcranial
      illumination at 5- to 15-s randomized intervals. Information theoretical indices,
      integration and interaction complexity, were calculated from the probability
      distribution of coincident spike patterns and used to quantify neuronal
      interactions before and after flash stimulation. RESULTS: Integration and
      complexity showed significant negative associations with desflurane concentration
      (N = 60). Flash stimulation increased integration and complexity at all
      anesthetic levels (N = 60); the effect on complexity was reduced in wakefulness.
      During stepwise withdrawal of desflurane, the largest increase in integration
      (74%) and poststimulus complexity (35%) occurred before reaching 4% desflurane
      concentration-a level associated with the recovery of consciousness according to
      the rats' righting reflex. CONCLUSIONS: Neuronal interactions in the cerebral
      cortex are augmented during emergence from anesthesia. Visual flash stimuli
      enhance neuronal interactions in both wakefulness and anesthesia; the increase in
      interaction complexity is attenuated as poststimulus complexity reaches plateau.
      The critical changes in cortical neuronal interactions occur during transition to
      consciousness.

PMID- 25955983
TI  - Assisted Ventilation in Patients with Acute Respiratory Distress Syndrome: Lung
      distending Pressure and Patient-Ventilator Interaction.
AB  - BACKGROUND: In patients with acute respiratory distress syndrome (ARDS), the use
      of assisted mechanical ventilation is a subject of debate. Assisted ventilation
      has benefits over controlled ventilation, such as preserved diaphragm function
      and improved oxygenation. Therefore, higher level of "patient control" of
      ventilator assist may be preferable in ARDS. However, assisted modes may also
      increase the risk of high tidal volumes and lung-distending pressures. The
      current study aims to quantify how differences in freedom to control the
      ventilator affect lung-protective ventilation, breathing pattern variability, and
      patient-ventilator interaction. METHODS: Twelve patients with ARDS were
      ventilated in a randomized order with assist pressure control ventilation (PCV),
      pressure support ventilation (PSV), and neurally adjusted ventilatory assist
      (NAVA). Transpulmonary pressure, tidal volume, diaphragm electrical activity, and
      patient-ventilator interaction were measured. Respiratory variability was
      assessed using the coefficient of variation of tidal volume. RESULTS: During
      inspiration, transpulmonary pressure was slightly lower with NAVA (10.3 +/- 0.7,
      11.2 +/- 0.7, and 9.4 +/- 0.7 cm H2O for PCV, PSV, and NAVA, respectively; P <
      0.01). Tidal volume was similar between modes (6.6 [5.7 to 7.0], 6.4 [5.8 to
      7.0], and 6.0 [5.6 to 7.3] ml/kg for PCV, PSV, and NAVA, respectively), but
      respiratory variability was higher with NAVA (8.0 [6.4 to 10.0], 7.1 [5.9 to
      9.0], and 17.0 [12.0 to 36.1] % for PCV, PSV, and NAVA, respectively; P < 0.001).
      Patient-ventilator interaction improved with NAVA (6 [5 to 8] % error) compared
      with PCV (29 [14 to 52] % error) and PSV (12 [9 to 27] % error); P < 0.0001.
      CONCLUSION: In patients with mild-to-moderate ARDS, increasing freedom to control
      the ventilator maintains lung-protective ventilation in terms of tidal volume and
      lung-distending pressure, but it improves patient-ventilator interaction and
      preserves respiratory variability.

PMID- 25955984
TI  - Monte Carlo Investigation of Optical Coherence Tomography Retinal Oximetry.
AB  - Optical coherence tomography (OCT) oximetry explores the possibility to measure
      retinal hemoglobin oxygen saturation level (sO2). We investigated the accuracy of
      OCT retinal oximetry using Monte Carlo simulation in a commonly used four-layer
      retinal model. After we determined the appropriate number of simulated photon
      packets, we studied the effects of blood vessel diameter, signal sampling
      position, physiological sO2 level, and the blood packing factor on the accuracy
      of sO2 estimation in OCT retinal oximetry. The simulation results showed that a
      packing factor between 0.2 and 0.4 yields a reasonably accurate estimation of sO2
      within a 5% error tolerance, which is independent of vessel diameter and sampling
      position, when visible-light illumination is used in OCT. We further explored the
      optimal optical spectral range for OCT retinal oximetry. The simulation results
      suggest that visible spectral range around 560 nm is better suited than near
      infrared spectral range around 800 nm for OCT oximetry to warrant accurate
      measurements. 

PMID- 25955985
TI  - Quantitative Analysis of Bladder Wall Thickness for Magnetic Resonance
      Cystoscopy.
AB  - OBJECTIVE: To find an effective way for quantitative evaluation on wall thickness
      variation of human bladder with/without bladder tumor, a novel pipeline of
      thickness measurement and analysis for magnetic resonance (MR) cystography is
      proposed. METHODS: After the acquisition of volumetric bladder images with a high
      resolution T2-weighted 3-D sequence, the inner and outer borders of the bladder
      wall were segmented simultaneously by a coupled directional level-set method.
      Then, the bladder wall thickness (BWT) was estimated using the Laplacian method.
      To reducing the influence of individual variation and urine filling on wall
      thickness, a thickness normalization using Z-score is performed. Finally, a
      parametric surface mapping strategy was applied to map thickness distribution
      onto a unified sphere surface, for quantitative intra- and intersubject
      comparison between bladders of different shapes. RESULTS: The proposed pipeline
      was tested with a database composed of MR bladder images acquired from 20
      volunteers and 20 patients with bladder cancer. The results indicate that the
      thickness normalization step using Z-score makes the quantitative comparison of
      wall thickness quite possible and there is a significant difference on BWT
      between patients and volunteers. Using the proposed pipeline, we established a
      thickness template for a normal bladder wall based on dataset of all volunteers.
      CONCLUSION: As a first attempt to establish a general pipeline for bladder wall
      analysis, the presented work provides an effective way to achieve the goal of
      evaluating the entire bladder wall for detection and diagnosis of abnormality. In
      addition, it can be easily extended to quantitative analyses of other bladder
      features, such as, intensity-based or texture features.

PMID- 25955986
TI  - Pharmacokinetic Modeling and Biodistribution Estimation Through the Molecular
      Communication Paradigm.
AB  - Targeted drug delivery systems (TDDSs) are therapeutic methods based on the
      injection and delivery of drug-loaded particles. The engineering of TDDSs must
      take into account both the therapeutic effects of the drug at the target delivery
      location and the toxicity of the drug while it accumulates in other regions of
      the body. These characteristics are directly related to how the drug-loaded
      particles distribute within the body, i.e., biodistribution, as a consequence of
      the processes involved in the particle propagation, i.e., pharmacokinetics. In
      this paper, the pharmacokinetics of TDDSs is analytically modeled through the
      abstraction of molecular communication, a novel paradigm in communication theory.
      Not only is the particle advection and diffusion, considered in our previous
      study, included in this model, but also are other physicochemical processes in
      the particle propagation, such as absorption, reaction, and adhesion. In
      addition, the proposed model includes the impact of cardiovascular diseases, such
      as arteriosclerosis and tumor-induced blood vessel leakage. Based on this model,
      the biodistribution at the delivery location is estimated through communication
      engineering metrics, such as channel delay and path loss, together with the drug
      accumulation in the rest of the body. The proposed pharmacokinetic model is
      validated against multiphysics finite-element simulations, and numerical results
      are provided for the biodistribution estimation in different scenarios. Finally,
      based on the proposed model, a procedure to optimize the drug injection rate is
      proposed to achieve a desired drug delivery rate. The outcome of this study is a
      multiscale physics-based analytical pharmacokinetic model. 

PMID- 25955988
TI  - Video deraining and desnowing using temporal correlation and low-rank matrix
      completion.
AB  - A novel algorithm to remove rain or snow streaks from a video sequence using
      temporal correlation and low-rank matrix completion is proposed in this paper.
      Based on the observation that rain streaks are too small and move too fast to
      affect the optical flow estimation between consecutive frames, we obtain an
      initial rain map by subtracting temporally warped frames from a current frame.
      Then, we decompose the initial rain map into basis vectors based on the sparse
      representation, and classify those basis vectors into rain streak ones and
      outliers with a support vector machine. We then refine the rain map by excluding
      the outliers. Finally, we remove the detected rain streaks by employing a low
      rank matrix completion technique. Furthermore, we extend the proposed algorithm
      to stereo video deraining. Experimental results demonstrate that the proposed
      algorithm detects and removes rain or snow streaks efficiently, outperforming
      conventional algorithms. 

PMID- 25955987
TI  - Temporal Sparse Promoting Three Dimensional Imaging of Cardiac Activation.
AB  - A new Cardiac Electrical Sparse Imaging (CESI) technique is proposed to image
      cardiac activation throughout the three-dimensional myocardium from body surface
      electrocardiogram (ECG) with the aid of individualized heart-torso geometry. The
      sparse property of cardiac electrical activity in the time domain is utilized in
      the temporal sparse promoting inverse solution, one formulated to achieve higher
      spatial-temporal resolution, stronger robustness and thus enhanced capability in
      imaging cardiac electrical activity. Computer simulations were carried out to
      evaluate the performance of this imaging method under various circumstances. A
      total of 12 single site pacing and 7 dual sites pacing simulations with
      artificial and the hospital recorded sensor noise were used to evaluate the
      accuracy and stability of the proposed method. Simulations with modeling error on
      heart-torso geometry and electrode-torso registration were also performed to
      evaluate the robustness of the technique. In addition to the computer
      simulations, the CESI algorithm was further evaluated using experimental data in
      an animal model where the noninvasively imaged activation sequences were compared
      with those measured with simultaneous intracardiac mapping. All of the CESI
      results were compared with conventional weighted minimum norm solutions. The
      present results show that CESI can image with better accuracy, stability and
      stronger robustness in both simulated and experimental circumstances. In sum, we
      have proposed a novel method for cardiac activation imaging, and our results
      suggest that the CESI has enhanced performance, and offers the potential to image
      the cardiac activation and to assist in the clinical management of ventricular
      arrhythmias. 

PMID- 25955989
TI  - An Analysis of Intrinsic and Extrinsic Hand Muscle EMG for Improved Pattern
      Recognition Control.
AB  - Pattern recognition control combined with surface electromyography (EMG) from the
      extrinsic hand muscles has shown great promise for control of multiple prosthetic
      functions for transradial amputees. There is, however, a need to adapt this
      control method when implemented for partial-hand amputees, who possess both a
      functional wrist and information-rich residual intrinsic hand muscles. We
      demonstrate that combining EMG data from both intrinsic and extrinsic hand
      muscles to classify hand grasps and finger motions allows up to 19 classes of
      hand grasps and individual finger motions to be decoded, with an accuracy of 96%
      for non-amputees and 85% for partial-hand amputees. We evaluated real-time
      pattern recognition control of three hand motions in seven different wrist
      positions. We found that a system trained with both intrinsic and extrinsic
      muscle EMG data, collected while statically and dynamically varying wrist
      position increased completion rates from 73% to 96% for partial-hand amputees and
      from 88% to 100% for non-amputees when compared to a system trained with only
      extrinsic muscle EMG data collected in a neutral wrist position. Our study shows
      that incorporating intrinsic muscle EMG data and wrist motion can significantly
      improve the robustness of pattern recognition control for application to partial
      hand prosthetic control. 

PMID- 25955990
TI  - Adaptive Threshold Neural Spike Detector Using Stationary Wavelet Transform in
      CMOS.
AB  - Spike detection is an essential first step in the analysis of neural recordings.
      Detection at the frontend eases the bandwidth requirement for wireless data
      transfer of multichannel recordings to extra-cranial processing units. In this
      work, a low power digital integrated spike detector based on the lifting
      stationary wavelet transform is presented and developed. By monitoring the
      standard deviation of wavelet coefficients, the proposed detector can adaptively
      set a threshold value online for each channel independently without requiring
      user intervention. A prototype 16-channel spike detector was designed and tested
      in an FPGA. The method enables spike detection with nearly 90% accuracy even when
      the signal-to-noise ratio is as low as 2. The design was mapped to 130 nm CMOS
      technology and shown to occupy 0.014 mm(2) of area and dissipate 1.7 MUW of power
      per channel, making it suitable for implantable multichannel neural recording
      systems.

PMID- 25955991
TI  - Tandem Stance Avoidance Using Adaptive and Asymmetric Admittance Control for Fall
      Prevention.
AB  - Fall prevention is one of the most important functions of walking assistance
      devices for user's safety. It is preferable that these devices prevent the user
      from being in the state where the risk of falling is high rather than helping
      them recovering from falling motion. During turning, when the user is in the
      tandem stance, a state where both legs form a line along walking direction, a
      support base that is surrounded by two legs becomes small, and a stability margin
      becomes small. This paper therefore aims to prevent the tandem stance by using
      nonwearable robot "intelligent cane" for the elderly or physically challenged
      person. Generally, the behavior of the lower limb follows the upper body turning.
      This paper therefore introduces a cane robot control method which constrains the
      behavior of user's upper body. By adjusting an admittance parameter of the robot
      according to the positions of a support leg, the robot resists to turn while a
      support leg is on the same side of the turning direction. A swing leg on the
      turning direction side therefore freely moves to the turning direction, while a
      swing leg on the opposite direction side of turning hardly move to the turning
      direction.

PMID- 25955992
TI  - Towards Microscale Flight: Fabrication, Stability Analysis, and Initial Flight
      Experiments for 300 MUm * 300 MUm * 1.5 MUm Sized Untethered MEMS Microfliers.
AB  - This paper presents modeling, designs, and initial experimental results
      demonstrating successful untethered microscale flight of stress-engineered
      microscale structures propelled by thermal forces. These MEMS Microfliers are 300
      MUm*300 MUm*1.5 MUm in size and are fabricated out of polycrystalline silicon
      using a surface micromachining process. A concave chassis, created using a novel
      in-situ masked post-release stress-engineering process, promotes static in-flight
      stability. High-speed optical micrography was used to capture image sequences of
      their flight, and this imagery was subsequently used to analyze their mid-flight
      performance. Our analysis, combined with finite element modeling (FEM) confirms
      stable flight of the microfliers within the thermal gradient above the heaters.
      This novel microscale flying platform presented in this paper may pave the way
      for new types of aerial microrobots.

PMID- 25955994
TI  - Robust Nonnegative Patch Alignment for Dimensionality Reduction.
AB  - Dimensionality reduction is an important method to analyze high-dimensional data
      and has many applications in pattern recognition and computer vision. In this
      paper, we propose a robust nonnegative patch alignment for dimensionality
      reduction, which includes a reconstruction error term and a whole alignment term.
      We use correntropy-induced metric to measure the reconstruction error, in which
      the weight is learned adaptively for each entry. For the whole alignment, we
      propose locality-preserving robust nonnegative patch alignment (LP-RNA) and
      sparsity-preserviing robust nonnegative patch alignment (SP-RNA), which are
      unsupervised and supervised, respectively. In the LP-RNA, we propose a locally
      sparse graph to encode the local geometric structure of the manifold embedded in
      high-dimensional space. In particular, we select large p -nearest neighbors for
      each sample, then obtain the sparse representation with respect to these
      neighbors. The sparse representation is used to build a graph, which
      simultaneously enjoys locality, sparseness, and robustness. In the SP-RNA, we
      simultaneously use local geometric structure and discriminative information, in
      which the sparse reconstruction coefficient is used to characterize the local
      geometric structure and weighted distance is used to measure the separability of
      different classes. For the induced nonconvex objective function, we formulate it
      into a weighted nonnegative matrix factorization based on half-quadratic
      optimization. We propose a multiplicative update rule to solve this function and
      show that the objective function converges to a local optimum. Several
      experimental results on synthetic and real data sets demonstrate that the learned
      representation is more discriminative and robust than most existing
      dimensionality reduction methods. 

PMID- 25955993
TI  - Physical and Perceptual Independence of Ultrasonic Vibration and Electrovibration
      for Friction Modulation.
AB  - Two different principles are available to modulate the user perceived roughness
      of a surface: electrovibration and ultrasonic vibration of a plate. The former
      enhances the perceived friction coefficient and the latter reduces it. This paper
      will highlight the independence of the two effects on the physical and perceptual
      point of view to confirm the increased range of sensation and stimulation that
      can be supplied by the two coupled techniques to the users. Firstly, a
      tribometric analysis of the induced lateral force on the finger by the two
      coupled effects will be presented, then a study on the dynamic of the two effects
      will be reported. In the end, a psychophysical experiment on the perception of
      the two coupled techniques will be shown. 

PMID- 25955995
TI  - Approximate Orthogonal Sparse Embedding for Dimensionality Reduction.
AB  - Locally linear embedding (LLE) is one of the most well-known manifold learning
      methods. As the representative linear extension of LLE, orthogonal neighborhood
      preserving projection (ONPP) has attracted widespread attention in the field of
      dimensionality reduction. In this paper, a unified sparse learning framework is
      proposed by introducing the sparsity or L1-norm learning, which further extends
      the LLE-based methods to sparse cases. Theoretical connections between the ONPP
      and the proposed sparse linear embedding are discovered. The optimal sparse
      embeddings derived from the proposed framework can be computed by iterating the
      modified elastic net and singular value decomposition. We also show that the
      proposed model can be viewed as a general model for sparse linear and nonlinear
      (kernel) subspace learning. Based on this general model, sparse kernel embedding
      is also proposed for nonlinear sparse feature extraction. Extensive experiments
      on five databases demonstrate that the proposed sparse learning framework
      performs better than the existing subspace learning algorithm, particularly in
      the cases of small sample sizes.

PMID- 25955996
TI  - Finite-Time Consensus for Multiagent Systems With Cooperative and Antagonistic
      Interactions.
AB  - This paper deals with finite-time consensus problems for multiagent systems that
      are subject to hybrid cooperative and antagonistic interactions. Two consensus
      protocols are constructed by employing the nearest neighbor rule. It is shown
      that under the presented protocols, the states of all agents can be guaranteed to
      reach an agreement in a finite time regarding consensus values that are the same
      in modulus but may not be the same in sign. In particular, the second protocol
      can enable all agents to reach a finite-time consensus with a settling time that
      is not dependent upon the initial states of agents. Simulation results are given
      to demonstrate the effectiveness and finite-time convergence of the proposed
      consensus protocols. 

PMID- 25955997
TI  - Model-Free Dual Heuristic Dynamic Programming.
AB  - Model-based dual heuristic dynamic programming (MB-DHP) is a popular approach in
      approximating optimal solutions in control problems. Yet, it usually requires
      offline training for the model network, and thus resulting in extra computational
      cost. In this brief, we propose a model-free DHP (MF-DHP) design based on finite
      difference technique. In particular, we adopt multilayer perceptron with one
      hidden layer for both the action and the critic networks design, and use delayed
      objective functions to train both the action and the critic networks online over
      time. We test both the MF-DHP and MB-DHP approaches with a discrete time example
      and a continuous time example under the same parameter settings. Our simulation
      results demonstrate that the MF-DHP approach can obtain a control performance
      competitive with that of the traditional MB-DHP approach while requiring less
      computational resources. 

PMID- 25955998
TI  - A Robust Deep Model for Improved Classification of AD/MCI Patients.
AB  - Accurate classification of Alzheimer's disease (AD) and its prodromal stage, mild
      cognitive impairment (MCI), plays a critical role in possibly preventing
      progression of memory impairment and improving quality of life for AD patients.
      Among many research tasks, it is of a particular interest to identify noninvasive
      imaging biomarkers for AD diagnosis. In this paper, we present a robust deep
      learning system to identify different progression stages of AD patients based on
      MRI and PET scans. We utilized the dropout technique to improve classical deep
      learning by preventing its weight coadaptation, which is a typical cause of
      overfitting in deep learning. In addition, we incorporated stability selection,
      an adaptive learning factor, and a multitask learning strategy into the deep
      learning framework. We applied the proposed method to the ADNI dataset, and
      conducted experiments for AD and MCI conversion diagnosis. Experimental results
      showed that the dropout technique is very effective in AD diagnosis, improving
      the classification accuracies by 5.9% on average as compared to the classical
      deep learning methods. 

PMID- 25955999
TI  - Estimation of respiratory rate from photoplethysmographic imaging videos compared
      to pulse oximetry.
AB  - We present a study evaluating two respiratory rate estimation algorithms using
      videos obtained from placing a finger on the camera lens of a mobile phone. The
      two algorithms, based on Smart Fusion and empirical mode decomposition (EMD),
      consist of previously developed signal processing methods to detect features and
      extract respiratory induced variations in photoplethysmographic signals to
      estimate respiratory rate. With custom-built software on an Android phone,
      photoplethysmographic imaging videos were recorded from 19 healthy adults while
      breathing spontaneously at respiratory rates between 6 to 32 breaths/min. Signals
      from two pulse oximeters were simultaneously recorded to compare the algorithms'
      performance using mobile phone data and clinical data. Capnometry was recorded to
      obtain reference respiratory rates. Two hundred seventy-two recordings were
      analyzed. The Smart Fusion algorithm reported 39 recordings with insufficient
      respiratory information from the photoplethysmographic imaging data. Of the 232
      remaining recordings, a root mean square error (RMSE) of 6 breaths/min was
      obtained. The RMSE for the pulse oximeter data was lower at 2.3 breaths/min. RMSE
      for the EMD method was higher throughout all data sources as, unlike the Smart
      Fusion, the EMD method did not screen for inconsistent results. The study showed
      that it is feasible to estimate respiratory rates by placing a finger on a mobile
      phone camera, but that it becomes increasingly challenging at respiratory rates
      greater than 20 breaths/min, independent of data source or algorithm tested. 

PMID- 25956000
TI  - A Fuzzy Kernel Motion Classifier for Autonomous Stroke Rehabilitation.
AB  - Autonomous poststroke rehabilitation systems which can be deployed outside
      hospital with no or reduced supervision have attracted increasing amount of
      research attentions due to the high expenditure associated with the current
      inpatient stroke rehabilitation systems. To realize an autonomous systems, a
      reliable patient monitoring technique which can automatically record and classify
      patient's motion during training sessions is essential. In order to minimize the
      cost and operational complexity, the combination of nonvisual-based inertia
      sensing devices and pattern recognition algorithms are often considered more
      suitable in such applications. However, the high motion irregularity due to
      stroke patients' body function impairment has significantly increased the
      classification difficulty. A novel fuzzy kernel motion classifier specifically
      designed for stroke patient's rehabilitation training motion classification is
      presented in this paper. The proposed classifier utilizes geometrically
      unconstrained fuzzy membership functions to address the motion class overlapping
      issue, and thus, it can achieve highly accurate motion classification even with
      poorly performed motion samples. In order to validate the performance of the
      classifier, experiments have been conducted using real motion data sampled from
      stroke patients with a wide range of impairment level and the results have
      demonstrated that the proposed classifier is superior in terms of error rate
      compared to other popular algorithms.

PMID- 25956001
TI  - Neural Network-Based Control of Networked Trilateral Teleoperation With
      Geometrically Unknown Constraints.
AB  - Most studies on bilateral teleoperation assume known system kinematics and only
      consider dynamical uncertainties. However, many practical applications involve
      tasks with both kinematics and dynamics uncertainties. In this paper, trilateral
      teleoperation systems with dual-master-single-slave framework are investigated,
      where a single robotic manipulator constrained by an unknown geometrical
      environment is controlled by dual masters. The network delay in the teleoperation
      system is modeled as Markov chain-based stochastic delay, then asymmetric
      stochastic time-varying delays, kinematics and dynamics uncertainties are all
      considered in the force-motion control design. First, a unified dynamical model
      is introduced by incorporating unknown environmental constraints. Then, by exact
      identification of constraint Jacobian matrix, adaptive neural network
      approximation method is employed, and the motion/force synchronization with time
      delays are achieved without persistency of excitation condition. The neural
      networks and parameter adaptive mechanism are combined to deal with the system
      uncertainties and unknown kinematics. It is shown that the system is stable with
      the strict linear matrix inequality-based controllers. Finally, the extensive
      simulation experiment studies are provided to demonstrate the performance of the
      proposed approach. 

PMID- 25956002
TI  - Evolving Scale-Free Networks by Poisson Process: Modeling and Degree
      Distribution.
AB  - Since the great mathematician Leonhard Euler initiated the study of graph theory,
      the network has been one of the most significant research subject in
      multidisciplinary. In recent years, the proposition of the small-world and scale
      free properties of complex networks in statistical physics made the network
      science intriguing again for many researchers. One of the challenges of the
      network science is to propose rational models for complex networks. In this
      paper, in order to reveal the influence of the vertex generating mechanism of
      complex networks, we propose three novel models based on the homogeneous Poisson,
      nonhomogeneous Poisson and birth death process, respectively, which can be
      regarded as typical scale-free networks and utilized to simulate practical
      networks. The degree distribution and exponent are analyzed and explained in
      mathematics by different approaches. In the simulation, we display the modeling
      process, the degree distribution of empirical data by statistical methods, and
      reliability of proposed networks, results show our models follow the features of
      typical complex networks. Finally, some future challenges for complex systems are
      discussed. 

PMID- 25956003
TI  - Brominated Flame Retardants and Other Persistent Organohalogenated Compounds in
      Relation to Timing of Puberty in a Longitudinal Study of Girls.
AB  - BACKGROUND: Exposure to hormonally active chemicals could plausibly affect
      pubertal timing, so we are investigating this in the Breast Cancer and the
      Environment Research Program. OBJECTIVES: Our goal was to examine persistent
      organic pollutants (POPs) in relation to pubertal onset. METHODS: Ethnically
      diverse cohorts of 6- to 8-year-old girls (n = 645) provided serum for measure of
      polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs),
      organochlorine pesticides (OCPs), and lipids. Tanner stages [breast (B) and pubic
      hair (PH)], and body mass index (BMI) were measured at up to seven annual clinic
      visits. Using accelerated failure time models, we calculated time ratios (TRs)
      for age at Tanner stages 2 or higher (2+) and POPs quartiles (Q1-4), adjusting
      for confounders (race/ethnicity, site, caregiver education, and income). We also
      calculated prevalence ratios (PRs) of Tanner stages 2+ at time of blood sampling.
      RESULTS: Cross-sectionally, the prevalence of B2+ and PH2+ was inversely related
      to chemical serum concentrations; but after adjustment for confounders, only the
      associations with B2+, not PH2+, were statistically significant. Longitudinally,
      the age at pubertal transition was consistently older with greater chemical
      concentrations; for example: adjusted TR for B2+ and Q4 for SigmaPBDE = 1.05; 95%
      CI: 1.02, 1.08, for SigmaPCB = 1.05; 95% CI: 1.01, 1.08, and for SigmaOCP = 1.10;
      95% CI: 1.06, 1.14, indicating median ages of about 6 and 11 months older than
      least exposed, and with similar effect estimates for PH2+. Adjusting for BMI
      attenuated associations for PCBs and OCPs but not for PBDEs. CONCLUSIONS: This
      first longitudinal study of puberty in girls with serum POPs measurements (to our
      knowledge) reveals a delay in onset with higher concentrations.

PMID- 25956004
TI  - Biased Exposure-Health Effect Estimates from Selection in Cohort Studies: Are
      Environmental Studies at Particular Risk?
AB  - BACKGROUND: The process of creating a cohort or cohort substudy may induce
      misleading exposure-health effect associations through collider stratification
      bias (i.e., selection bias) or bias due to conditioning on an intermediate.
      Studies of environmental risk factors may be at particular risk. OBJECTIVES: We
      aimed to demonstrate how such biases of the exposure-health effect association
      arise and how one may mitigate them. METHODS: We used directed acyclic graphs and
      the example of bone lead and mortality (all-cause, cardiovascular, and ischemic
      heart disease) among 835 white men in the Normative Aging Study (NAS) to
      illustrate potential bias related to recruitment into the NAS and the bone lead
      substudy. We then applied methods (adjustment, restriction, and inverse
      probability of attrition weighting) to mitigate these biases in analyses using
      Cox proportional hazards models to estimate adjusted hazard ratios (HRs) and 95%
      confidence intervals (CIs). RESULTS: Analyses adjusted for age at bone lead
      measurement, smoking, and education among all men found HRs (95% CI) for the
      highest versus lowest tertile of patella lead of 1.34 (0.90, 2.00), 1.46 (0.86,
      2.48), and 2.01 (0.86, 4.68) for all-cause, cardiovascular, and ischemic heart
      disease mortality, respectively. After applying methods to mitigate the biases,
      the HR (95% CI) among the 637 men analyzed were 1.86 (1.12, 3.09), 2.47 (1.23,
      4.96), and 5.20 (1.61, 16.8), respectively. CONCLUSIONS: Careful attention to the
      underlying structure of the observed data is critical to identifying potential
      biases and methods to mitigate them. Understanding factors that influence initial
      study participation and study loss to follow-up is critical. Recruitment of
      population-based samples and enrolling participants at a younger age, before the
      potential onset of exposure-related health effects, can help reduce these
      potential pitfalls. CITATION: Weisskopf MG, Sparrow D, Hu H, Power MC. 2015.
      Biased exposure-health effect estimates from selection in cohort studies: are
      environmental studies at particular risk? Environ Health Perspect 123:1113-1122;
      http://dx.doi.org/10.1289/ehp.1408888.

PMID- 25956005
TI  - Prospective Study of Ambient Particulate Matter Exposure and Risk of Pulmonary
      Embolism in the Nurses' Health Study Cohort.
AB  - BACKGROUND: Pulmonary embolism (PE) is the most serious manifestation of venous
      thromboembolism and a leading cause of sudden death. Several studies have
      suggested associations of venous thromboembolism with short-term particulate
      matter (PM) exposure; evidence on long-term PM and traffic exposure is mixed.
      OBJECTIVES: We examined the association of long-term exposure to PM2.5, PM2.5-10,
      and PM10 (PM with diameter of <= 2.5, 2.5-10, and <= 10 MUm) and distance to
      roadways with overall incident PE and with PE subtypes in a cohort of U.S. women.
      METHODS: The study included 115,745 women from the Nurses' Health Study, followed
      from 1992 through 2008. Incident PE cases were self-reported biennially.
      Nonidiopathic PE were cases for which the medical record revealed an underlying
      health condition related to PE (i.e., surgery, trauma, or malignancy); idiopathic
      PE were cases with no such history. We used spatiotemporal models combining
      spatial smoothing and geographic covariates to quantify exposure at residential
      addresses, and Cox proportional hazards models to calculate hazard ratios (HR)
      and 95% confidence intervals (CIs). RESULTS: PM2.5 averaged over 1 month (HR =
      1.22; 95% CI: 1.04, 1.44) or 12 months (HR = 1.17; 95% CI: 0.93, 1.48) was
      associated with incident PE, after adjusting for known risk factors and PM2.5-10.
      Equivalent analyses restricted to PE subtypes showed a positive association for
      PM2.5 with nonidiopathic PE, but not with idiopathic PE. We did not find evidence
      of an association between distance to roadways and PE risk. CONCLUSIONS: We
      provide evidence that PM in the prior 1 and 12 months is associated with PE risk.
      Our results also suggest that women with underlying health conditions may be more
      susceptible to PE after PM exposure.

PMID- 25956006
TI  - Association of Supply Type with Fecal Contamination of Source Water and Household
      Stored Drinking Water in Developing Countries: A Bivariate Meta-analysis.
AB  - BACKGROUND: Access to safe drinking water is essential for health. Monitoring
      access to drinking water focuses on water supply type at the source, but there is
      limited evidence on whether quality differences at the source persist in water
      stored in the household. OBJECTIVES: We assessed the extent of fecal
      contamination at the source and in household stored water (HSW) and explored the
      relationship between contamination at each sampling point and water supply type.
      METHODS: We performed a bivariate random-effects meta-analysis of 45 studies,
      identified through a systematic review, that reported either the proportion of
      samples free of fecal indicator bacteria and/or individual sample bacteria counts
      for source and HSW, disaggregated by supply type. RESULTS: Water quality
      deteriorated substantially between source and stored water. The mean percentage
      of contaminated samples (noncompliance) at the source was 46% (95% CI: 33, 60%),
      whereas mean noncompliance in HSW was 75% (95% CI: 64, 84%). Water supply type
      was significantly associated with noncompliance at the source (p < 0.001) and in
      HSW (p = 0.03). Source water (OR = 0.2; 95% CI: 0.1, 0.5) and HSW (OR = 0.3; 95%
      CI: 0.2, 0.8) from piped supplies had significantly lower odds of contamination
      compared with non-piped water, potentially due to residual chlorine. CONCLUSIONS:
      Piped water is less likely to be contaminated compared with other water supply
      types at both the source and in HSW. A focus on upgrading water services to piped
      supplies may help improve safety, including for those drinking stored water.

PMID- 25956007
TI  - Exposure to Endocrine-Disrupting Chemicals during Pregnancy and Weight at 7 Years
      of Age: A Multi-pollutant Approach.
AB  - BACKGROUND: Prenatal exposure to endocrine-disrupting chemicals (EDCs) may induce
      weight gain and obesity in children, but the obesogenic effects of mixtures have
      not been studied. OBJECTIVE: We evaluated the associations between pre- and
      perinatal biomarker concentrations of 27 EDCs and child weight status at 7 years
      of age. METHODS: In pregnant women enrolled in a Spanish birth cohort study
      between 2004 and 2006, we measured the concentrations of 10 phthalate
      metabolites, bisphenol A, cadmium, arsenic, and lead in two maternal pregnancy
      urine samples; 6 organochlorine compounds in maternal pregnancy serum; mercury in
      cord blood; and 6 polybrominated diphenyl ether congeners in colostrum. Among 470
      children at 7 years, body mass index (BMI) z-scores were calculated, and
      overweight was defined as BMI > 85th percentile. We estimated associations with
      EDCs in single-pollutant models and applied principal-component analysis (PCA) on
      the 27 pollutant concentrations. RESULTS: In single-pollutant models, HCB
      (hexachlorobenzene), betaHCH (beta-hexachlorocyclohexane), and polychlorinated
      biphenyl (PCB) congeners 138 and 180 were associated with increased child BMI z
      scores; and HCB, betaHCH, PCB-138, and DDE (dichlorodiphenyldichloroethylene)
      with overweight risk. PCA generated four factors that accounted for 43.4% of the
      total variance. The organochlorine factor was positively associated with BMI z
      scores and with overweight (adjusted RR, tertile 3 vs. 1: 2.59; 95% CI: 1.19,
      5.63), and these associations were robust to adjustment for other EDCs. Exposure
      in the second tertile of the phthalate factor was inversely associated with
      overweight. CONCLUSIONS: Prenatal exposure to organochlorines was positively
      associated with overweight at age 7 years in our study population. Other EDCs
      exposures did not confound this association.

PMID- 25956008
TI  - Bidirectional Transfer Study of Polystyrene Nanoparticles across the Placental
      Barrier in an ex Vivo Human Placental Perfusion Model.
AB  - BACKGROUND: Nanoparticle exposure in utero might not be a major concern yet, but
      it could become more important with the increasing application of nanomaterials
      in consumer and medical products. Several epidemiologic and in vitro studies have
      shown that nanoparticles can have potential toxic effects. However, nanoparticles
      also offer the opportunity to develop new therapeutic strategies to treat
      specifically either the pregnant mother or the fetus. Previous studies mainly
      addressed whether nanoparticles are able to cross the placental barrier. However,
      the transport mechanisms underlying nanoparticle translocation across the
      placenta are still unknown. OBJECTIVES: In this study we examined which transport
      mechanisms underlie the placental transfer of nanoparticles. METHODS: We used the
      ex vivo human placental perfusion model to analyze the bidirectional transfer of
      plain and carboxylate modified polystyrene particles in a size range between 50
      and 300 nm. RESULTS: We observed that the transport of polystyrene particles in
      the fetal to maternal direction was significantly higher than for the maternal to
      fetal direction. Regardless of their ability to cross the placental barrier and
      the direction of perfusion, all polystyrene particles accumulated in the
      syncytiotrophoblast of the placental tissue. CONCLUSIONS: Our results indicate
      that the syncytiotrophoblast is the key player in regulating nanoparticle
      transport across the human placenta. The main mechanism underlying this
      translocation is not based on passive diffusion, but is likely to involve an
      active, energy-dependent transport pathway. These findings will be important for
      reproductive toxicology as well as for pharmaceutical engineering of new drug
      carriers.

PMID- 25956009
TI  - Chemical Safety Assessment Using Read-Across: Assessing the Use of Novel Testing
      Methods to Strengthen the Evidence Base for Decision Making.
AB  - BACKGROUND: Safety assessment for repeated dose toxicity is one of the largest
      challenges in the process to replace animal testing. This is also one of the
      proof of concept ambitions of SEURAT-1, the largest ever European Union research
      initiative on alternative testing, co-funded by the European Commission and
      Cosmetics Europe. This review is based on the discussion and outcome of a
      workshop organized on initiative of the SEURAT-1 consortium joined by a group of
      international experts with complementary knowledge to further develop traditional
      read-across and include new approach data. OBJECTIVES: The aim of the suggested
      strategy for chemical read-across is to show how a traditional read-across based
      on structural similarities between source and target substance can be
      strengthened with additional evidence from new approach data--for example,
      information from in vitro molecular screening, "-omics" assays and computational
      models--to reach regulatory acceptance. METHODS: We identified four read-across
      scenarios that cover typical human health assessment situations. For each such
      decision context, we suggested several chemical groups as examples to prove when
      read-across between group members is possible, considering both chemical and
      biological similarities. CONCLUSIONS: We agreed to carry out the complete read
      across exercise for at least one chemical category per read-across scenario in
      the context of SEURAT-1, and the results of this exercise will be completed and
      presented by the end of the research initiative in December 2015.

PMID- 25956010
TI  - Evaluation of an Elementary School-based Educational Intervention for Reducing
      Arsenic Exposure in Bangladesh.
AB  - BACKGROUND: Chronic exposure to well water arsenic (As) remains a major rural
      health challenge in Bangladesh and some other developing countries. Many
      mitigation programs have been implemented to reduce As exposure, although
      evaluation studies for these efforts are rare in the literature. OBJECTIVES: In
      this study we estimated associations between a school-based intervention and
      various outcome measures of As mitigation. METHODS: We recruited 840 children
      from 14 elementary schools in Araihazar, Bangladesh. Teachers from 7 schools were
      trained on an As education curriculum, whereas the remaining 7 schools without
      any training formed the control group. Surveys, knowledge tests, and well-water
      testing were conducted on 773 children both at baseline and postintervention
      follow-up. Urine samples were collected from 210 children from 4 intervention
      schools and the same number of children from 4 control schools. One low-As (< 10
      MUg/L) community well in each study village was ensured during an 18-month
      intervention period. RESULTS: After adjustment for the availability of low-As
      wells and other sociodemographic confounders, children receiving the intervention
      were five times more likely to switch from high- to low-As wells (p < 0.001). We
      also observed a significant decline of urinary arsenic (UAs) (p = < 0.001)
      (estimated beta = -214.9; 95% CI: -301.1, -128.7 MUg/g creatinine) among the
      children who were initially drinking from high-As wells (> Bangladesh standard of
      50 MUg/L) and significantly improved As knowledge attributable to the
      intervention after controlling for potential confounders. CONCLUSIONS: These
      findings offer strong evidence that school-based intervention can effectively
      reduce As exposure in Bangladesh by motivating teachers, children, and parents.

PMID- 25956011
TI  - Transparency of outcome reporting and trial registration of randomized controlled
      trials in top psychosomatic and behavioral health journals: A 5-year follow-up.
AB  - OBJECTIVE: The extent that randomized controlled trials (RCTs) accurately reflect
      intervention effectiveness depends on the completeness and accuracy of published
      results. A previous study found that only 40% of 63 RCTs published in top
      behavioral health journals in 2008-2009 clearly declared primary and secondary
      outcomes and only 21% were registered. The objective of this study was to conduct
      a five-year follow-up to assess outcome reporting clarity, proportion of
      registered trials, and adequacy of outcome registration in RCTs in top behavioral
      health journals. METHOD: Eligible studies were RCTs published in Annals of
      Behavioral Medicine, Health Psychology, Journal of Psychosomatic Research, and
      Psychosomatic Medicine from January 2013 to October 2014. RESULTS: Of 76 RCT
      publications reviewed, only 25 (32.9%) adequately declared primary or secondary
      outcomes, whereas 51 (67.1%) had multiple primary outcomes or did not define
      outcomes. Of the 76 trials, 40 (52.6%) had been registered. Only 3 studies
      registered a single primary outcome and time point of assessment prior to
      enrolling patients, and registered and published outcomes were discrepant in 1 of
      the 3 studies. No studies were adequately registered as per Standard Protocol
      Items: Recommendation for Interventional Trials guidelines. Compared to 5 years
      prior, the proportion of published trials with adequate outcome declaration
      decreased from 39.7% to 32.9% (p=0.514). The proportion of registered trials
      increased from 20.6% to 52.6% (p<0.001). CONCLUSION: The quality of published
      outcome declarations and trial registrations remains largely inadequate. Greater
      attention to trial registration and outcome definition in published reports is
      needed.

PMID- 25956012
TI  - Celiac disease.
AB  - This review will focus on the pathogenesis, clinical manifestations, diagnosis,
      and management of celiac disease (CD). Given an increasing awareness of gluten
      related disorders, medical professionals of all varieties are encountering
      patients with a diagnosis of CD or who are thought to have food intolerance to
      gluten. The prevalence of CD among the general population is estimated to be 1%
      in Western nations, and there is growing evidence for underdiagnosis of the
      disease, especially in non-Western nations that were traditionally believed to be
      unaffected. The development of serologic markers specific to CD has
      revolutionized the ability both to diagnose and monitor patients with the
      disease. Additionally, understanding of the clinical presentations of CD has
      undergone a major shift over the past half century. Although it is well
      understood that CD develops in genetically predisposed subjects exposed to
      gluten, the extent of other environmental factors in the pathogenesis of the
      disease is an area of continued research. Currently, the main therapeutic
      intervention for CD is a gluten-free diet; however, novel nondietary agents are
      under active investigation. Future areas of research should also help us
      understand the relationship of CD to other gluten-related disorders. 

PMID- 25956013
TI  - Non-IgE-mediated gastrointestinal food allergy.
AB  - Non-IgE-mediated gastrointestinal food-induced allergic disorders (non-IgE-GI
      FAs) account for an unknown proportion of food allergies and include food protein
      induced enterocolitis syndrome (FPIES), food protein-induced allergic
      proctocolitis (FPIAP), and food protein-induced enteropathy (FPE). Non-IgE-GI-FAs
      are separate clinical entities but have many overlapping clinical and histologic
      features among themselves and with eosinophilic gastroenteropathies. Over the
      past decade, FPIES has emerged as the most actively studied non-IgE-GI-FA,
      potentially because of acute and distinct clinical features. FPIAP remains among
      the common causes of rectal bleeding in infants, while classic infantile FPE is
      rarely diagnosed. The overall most common allergens are cow's milk and soy; in
      patients with FPIES, rice and oat are also common. The most prominent clinical
      features of FPIES are repetitive emesis, pallor, and lethargy; chronic FPIES can
      lead to failure to thrive. FPIAP manifests with bloody stools in well-appearing
      young breast-fed or formula-fed infants. Features of FPE are nonbloody diarrhea,
      malabsorption, protein-losing enteropathy, hypoalbuminemia, and failure to
      thrive. Non-IgE-GI-FAs have a favorable prognosis; the majority resolve by 1 year
      in patients with FPIAP, 1 to 3 years in patients with FPE, and 1 to 5 years in
      patients with FPIES, with significant differences regarding specific foods. There
      is an urgent need to better define the natural history of FPIES and the
      pathophysiology of non-IgE-GI-FAs to develop biomarkers and novel therapies.

PMID- 25956014
TI  - Advances in basic and clinical immunology in 2014.
AB  - Genetic identification of immunodeficiency syndromes has become more efficient
      with the availability of whole-exome sequencing, expediting the identification of
      relevant genes and complementing traditional linkage analysis and homozygosity
      mapping. New genes defects causing immunodeficiency include phophoglucomutase 3
      (PGM3), cytidine 5' triphosphate synthase 1 (CTPS1), nuclear factor kappaB
      inducing kinase (NIK), cytotoxic T lymphocyte-associated antigen 4 (CTLA4), B
      cell chronic lymphocytic leukemia/lymphoma 10 (BCL10), phosphoinositide-3 kinase
      regulatory subunit 1 (PIK3R1), IL21, and Jagunal homolog 1 (JAGN1). New case
      reports expanded the clinical spectrum of gene defects. For example, a specific
      recombination-activating gene 1 variant protein with partial recombinant activity
      might produce Omenn syndrome or a common variable immunodeficiency phenotype.
      Central and peripheral B-cell tolerance was investigated in patients with several
      primary immunodeficiencies, including common variable immunodeficiency and
      Wiskott-Aldrich syndrome, to explain the occurrence of autoimmunity and
      inflammatory disorders. The role of IL-12 and IL-15 in the enhancement of natural
      killer cell activity was reported. Newborn screening for T-cell deficiency is
      being implemented in more states and is achieving its goal of defining the true
      incidence of severe combined immunodeficiency and providing early treatment that
      offers the highest survival for these patients. Definitive treatment of severe
      immunodeficiency with both hematopoietic stem cell transplantation and gene
      therapy was reported to be successful, with increasing definition of conditions
      needed for optimal outcomes. Progress in HIV infection is directed toward the
      development of an effective vaccine and the eradication of hidden latent virus
      reservoirs. 

PMID- 25956016
TI  - Social relationships and risk of dementia: A systematic review and meta-analysis
      of longitudinal cohort studies.
AB  - It is unclear to what extent poor social relationships are related to the
      development of dementia. A comprehensive systematic literature search identified
      19 longitudinal cohort studies investigating the association between various
      social relationship factors and incident dementia in the general population.
      Relative risks (RRs) with 95% confidence intervals (CIs) were pooled using random
      effects meta-analysis. Low social participation (RR: 1.41 (95% CI: 1.13-1.75)),
      less frequent social contact (RR: 1.57 (95% CI: 1.32-1.85)), and more loneliness
      (RR: 1.58 (95% CI: 1.19-2.09)) were statistically significant associated with
      incident dementia. The results of the association between social network size and
      dementia were inconsistent. No statistically significant association was found
      for low satisfaction with social network and the onset of dementia (RR: 1.25 (95%
      CI: 0.96-1.62). We conclude that social relationship factors that represent a
      lack of social interaction are associated with incident dementia. The strength of
      the associations between poor social interaction and incident dementia is
      comparable with other well-established risk factors for dementia, including low
      education attainment, physical inactivity, and late-life depression. 

PMID- 25956017
TI  - A Brief Educational Intervention Increases Knowledge of the Sugar Content of
      Foods and Drinks but Does Not Decrease Intakes in Scottish Children Aged 10-12
      Years.
AB  - OBJECTIVE: To assess the effectiveness of an educational intervention to improve
      children's knowledge of the sugar content of food and beverages. METHODS: Cluster
      randomized, controlled trial with 268 children (aged 10-12 years) from 14 primary
      schools in Aberdeen, Scotland. The intervention group received 2 interactive
      classroom sessions about sugar. A questionnaire to assess knowledge was completed
      at baseline and 4, 10, and 34 weeks postintervention. Dietary intake was assessed
      by food frequency questionnaire at baseline and on weeks 10 and 34. RESULTS:
      After the intervention, the intervention group demonstrated greater knowledge of
      sugar than did the control group (P < .001), which was sustained at week 34 (P <
      .001). Dietary intakes of sugar did not change postintervention. Pre-intervention
      children underestimated the sugar content of fruit-based beverages. CONCLUSIONS
      AND IMPLICATIONS: Children's knowledge of sugar in food and beverages is limited
      but can be improved through a simple educational intervention. Further
      intervention would be needed to encourage a change in dietary intake.

PMID- 25956018
TI  - Respiratory syncytial virus as a cause of acute respiratory infections in adults.
      An emerging disease?

PMID- 25956019
TI  - Absorbable Screws Versus Metallic Screws for Distal Tibiofibular Syndesmosis
      Injuries: A Meta-Analysis.
AB  - A meta-analysis was performed to investigate the outcomes between absorbable
      screw (AS) and metallic screw (MS) fixation for distal tibiofibular syndesmosis
      injuries (DTSIs). Randomized controlled trials comparing AS versus MS fixation in
      DTSIs were searched systematically, and the outcomes were analyzed using Review
      Manager Software, version 5.2. The risk ratio (RR) or mean difference with the
      95% confidence interval (CI) was calculated using the fixed effects or random
      effects model. A total of 16 studies were included in the meta-analysis. No
      statistically significant difference was found between AS and MS fixation in
      excellent and good functional recovery rate (RR 1.11, 95% CI 1.00 to 1.23, I(2) =
      60%, p = .06), infection (RR 1.66, 95% CI 0.73 to 3.79, I(2) = 0%, p = .23),
      incidence of pain (RR 0.68, 95% CI 0.24 to 1.92, I(2) = 12%, p = .47), screw
      broken (RR 0.31, 95% CI 0.03 to 2.93, I(2) = %, p = .31), heterotopic
      ossification (RR 1.93, 95% CI 0.21 to 17.62, I(2) = 51%, p = .56; 472 cases in 4
      studies), fracture healing time (mean difference -1.88, 95% CI -3.51 to -0.26,
      I(2) = 93%, p = .02,), duration of operation time (mean difference 7.64, 95% CI 
      3.80 to 19.09, I(2) = 98%, p = .19). The incidence of foreign body reaction was
      higher with AS fixation (RR 6.07, 95% CI 2.54 to 14.50, I(2) = 0%, p < .001). The
      reoperation rate was higher with MS fixation (RR 0.08, 95% CI 0.03 to 0.18, I(2)
      = 77%, p < .01). The functional outcomes of AS were as good as those with MS for
      DTSIs. Other than the foreign body reaction, the complications occurring after AS
      fixation were not as serious as those with MS fixation. AS fixation might be a
      preferable alternative for reconstruction of DTSIs.

PMID- 25956020
TI  - Validation of test performance characteristics and minimal clinically important
      difference of the 6-minute walk test in patients with idiopathic pulmonary
      fibrosis.
AB  - BACKGROUND: The 6-minute walk test distance (6MWD) has been shown to be a valid
      and responsive outcome measure in patients with idiopathic pulmonary fibrosis
      (IPF). The analyses were based, however, on a single phase 3 trial and require
      validation in an independent cohort. OBJECTIVE: To confirm the performance
      characteristics and estimates of minimal clinically important difference (MCID)
      of 6MWD in an independent cohort of patients with IPF. METHODS: Patients
      randomized to placebo in the phase 3 CAPACITY trials who had a baseline 6MWD
      measurement were included in these analyses. The 6MWD and other functional
      parameters (lung function, dyspnea, and health-related quality of life) were
      measured at baseline and 24-week intervals. Validity and responsiveness were
      examined using Spearman correlation coefficients. The MCID was estimated using
      distribution- and anchor-based methods. RESULTS: The analysis comprised 338
      patients. Baseline 6MWD was significantly correlated with lung function measures,
      patient-reported outcomes, and quality-of-life measures (validity). Compared with
      baseline 6MWD, change in 6MWD (responsiveness) showed stronger correlations with
      change in lung function parameters and quality-of-life measures. Dyspnea measured
      by the University of California San Diego Shortness of Breath Questionnaire
      showed the strongest correlations with 6MWD (baseline: coefficient -0.35; 48-week
      change: coefficient -0.37; both p < 0.001). The distribution-based analyses of
      MCID using standard error of measurement yielded an MCID of 37 m, and
      distribution-based analyses by effect size resulted in 29.2 m. The MCID by anchor
      based analysis using criterion referencing (health events of hospitalization or
      death) was 21.7 m. CONCLUSIONS: The 6MWD is a valid and responsive clinical
      endpoint, which provides objective and clinically meaningful information
      regarding functional status and near-term prognosis. These results confirm
      previous findings in an independent cohort of patients with IPF.

PMID- 25956021
TI  - Outcomes in patients with community-acquired pneumonia admitted to the intensive
      care unit.
AB  - INTRODUCTION: Severe community-acquired pneumonia (CAP) portends a serious
      prognosis. The temporal trend in outcome of severe CAP is not well established.
      We evaluated the temporal trends in the outcomes of severe CAP. METHODS: This is
      a secondary analysis of 800 patients with severe CAP enrolled in the Community
      Acquired Pneumonia Organization International Cohort. Severe CAP was defined as
      CAP requiring admission to the intensive care unit. Only patients admitted to the
      ICU upon hospital admission were included in this study. We assessed the trend in
      outcomes of these patients during three time periods: Period I (June 2001 to
      April 2004), Period II (May 2004 to January 31 2008), and Period III (February
      2008 to February 2013). RESULTS: After adjustment for other variables, mortality
      was higher for patients admitted during Period II compared with Period I (RR:
      1.46; 95% CI: 1.002 to 2.14; P value = 0.049), and for Period III compared with
      Period I (RR: 1.70; 95% CI: 1.15 to 2.50; P value = 0.008). No significant
      difference in length of stay or time to clinical stability was found among the
      three periods. CONCLUSION: The mortality of patients with severe CAP increased
      over time in our study population. This finding has important health policy
      implications if confirmed by other studies.

PMID- 25956022
TI  - Evaluation of water sampling methodologies for amplicon-based characterization of
      bacterial community structure.
AB  - Reduction in costs of next-generation sequencing technologies has allowed
      unprecedented characterization of bacterial communities from environmental
      samples including aquatic ecosystems. However, the extent to which extrinsic
      factors including sampling volume, sample replication, DNA extraction kits, and
      sequencing target affect the community structure inferred are poorly explored.
      Here, triplicate 1, 2, and 6L volume water samples from the Upper Mississippi
      River were processed to determine variation among replicates and sample volumes.
      Replicate variability significantly influenced differences in the community alpha
      diversity (P=0.046), while volume significantly changed beta-diversity (P=0.037).
      Differences in phylogenetic and taxonomic community structure differed both among
      triplicate samples and among the volumes filtered. Communities from 2L and 6L
      water samples showed similar clustering via discriminant analysis. To assess
      variation due to DNA extraction method, DNA was extracted from triplicate cell
      pellets from four sites along the Upper Mississippi River using the Epicentre
      Metagenomic DNA Isolation Kit for Water and MoBio PowerSoil kit. Operational
      taxonomic units representing <=14% of sequence reads differed significantly among
      all sites and extraction kits used, although differences in diversity and
      community coverage were not significant (P>=0.057). Samples characterized using
      only the V6 region had significantly higher coverage and lower richness and alpha
      diversity than those characterized using V4-V6 regions (P<0.001). Triplicate
      sampling of at least 2L of water provides robust representation of community
      variability, and these results indicate that DNA extraction kit and sequencing
      target displayed taxonomic biases that did not affect the overall biological
      conclusions drawn.

PMID- 25956023
TI  - Carbon nanomaterial-based electrochemical biosensors for label-free sensing of
      environmental pollutants.
AB  - Carbon allotropes such as graphene and carbon nanotubes, have been incorporated
      in electrochemical biosensors for highly sensitive and selective detection of
      various analytes. The superior physical and electrical properties like high
      carrier mobility, ambipolar electric field effect, high surface area, flexibility
      and their compatibility with microfabrication techniques makes these carbon
      nanomaterials easy to integrate in field-effect transistor (FET)/chemiresistor
      type configuration which is suitable for portable and point-of-use/field
      deployable sensors. This review covers the synthesis of carbon nanostructures
      (graphene and CNTs) and their integration into devices using various fabrication
      methods. Finally, we discuss the recent reports showing different sensing
      platforms that incorporate biomolecules like enzymes, antibodies and aptamers as
      recognition elements for fabrication of simple, low cost, compact biosensors that
      can be used for on-site, rapid environmental monitoring of environmental
      pollutants like pathogens, heavy metals, pesticides and explosives. 

PMID- 25956024
TI  - The effect of titanium dioxide (TiO2) nano-objects, and their aggregates and
      agglomerates greater than 100nm (NOAA) on microbes under UV irradiation.
AB  - Today, nanoparticles are used in many products. One of the most common
      nanoparticles is titanium dioxide (TiO2). These particles generate reactive
      oxygen species (ROS) upon UV irradiation. Although nanoparticles are very useful
      in many products, there are concerns about their biological and ecological
      effects when released into the environment. Thus, it was assessed that the effect
      of TiO2 nano-objects, and their aggregates and agglomerates greater than 100nm
      (NOAA) on microbes under UV irradiation by using Escherichia coli and
      Saccharomyces cerevisiae. ROS generation was evaluated by adding TiO2
      nanoparticles and methylene blue to distilled water. We also assessed growth
      inhibition by adding TiO2 nanoparticles and microbes in minimal agar medium.
      Moreover, microbial inactivation was assessed by adding TiO2 nanoparticles and
      microbes to PBS. Upon UV irradiation, TiO2-NOAAs decomposed methylene blue and
      generated ROS. TiO2-NOAAs also decomposed methylene blue in minimal agar medium
      under UV irradiation; however, they did not inhibit microbial growth.
      Surprisingly, TiO2-NOAAs in the medium protect microbes from UV irradiation as
      colony formation was observed only near TiO2-NOAAs. In PBS, TiO2-NOAAs did not
      inactivate microbes but instead protected microbes from lethal UV irradiation.
      These results suggest that the amount of ROS generated by TiO2-NOAAs is not
      enough to inactivate microbes. In fact, our results suggest that TiO2-NOAAs may
      protect microbes from UV irradiations. 

PMID- 25956025
TI  - Treatment of sites contaminated with perfluorinated compounds using biochar
      amendment.
AB  - Per- and polyfluorinated compounds (PFCs) have been attracting increasing
      attention due to their considerable persistence, bioaccumulation, and toxicity.
      Here, we studied the sorption behavior of three PFCs, viz.
      perfluorooctanesulfonic acid (PFOS), perfluorooctanecarboxylic acid (PFOA),
      perfluorohexanesulfonic acid (PFHxS), on one activated carbon (AC) and two
      biochars from different feedstocks, viz. mixed wood (MW) and paper mill waste
      (PMW). In addition, we explored the potential of remediating three natively PFC
      contaminated soils by the addition of AC or biochar. The sorption coefficient
      i.e. Freundlich coefficients LogKF, (MUg/kg)/(MUg/L)(n), for the two biochars
      were 4.61+/-0.11 and 4.41+/-0.05 for PFOS, 3.02+/-0.04 and 3.01+/-0.01 for PFOA,
      and 3.21+/-0.07 and 3.18+/-0.03 for PFHxS, respectively. The AC sorbed the PFCs
      so strongly that aqueous concentrations were reduced to below detection limits,
      implying that the LogKF values were above 5.60. Sorption capacities decreased in
      the order: AC>MW>PMW, which was consistent with the material's surface area and
      pore size distribution. PFC sorption to MW biochar was near-linear (Freundlich
      exponent nF of 0.87-0.90), but non-linear for PMW biochar (0.64-0.73). Addition
      of the AC to contaminated soils resulted in almost complete removal of PFCs from
      the water phase and a significant (i.e. 1-3 Log unit) increase in soil-water
      distribution coefficient LogKd. However, small to no reduction in pore water
      concentration, and no effect on LogKd was found for the biochars. We conclude
      that amendment with AC but not biochar can be a useful method for in situ
      remediation of PFC-contaminated soils.

PMID- 25956026
TI  - An urgent need for building technical capacity for rapid diagnosis of multidrug
      resistant tuberculosis (MDR-TB) among new cases: A case report from Maharashtra,
      India.
AB  - Multidrug-resistant tuberculosis (MDR-TB), the prevalence of which has increased
      across the globe in recent years, is a serious threat to public health. Timely
      diagnosis of MDR-TB, especially among new TB cases, is essential to facilitate
      appropriate treatment, which can prevent further emergence of drug resistance and
      its spread in the population. The present case report from India aims to address
      some operational challenges in diagnosing MDR-TB among new cases and potential
      measures to overcome them. It argues that even after seven years of implementing
      the DOTS-Plus program for controlling MDR-TB, India still lacks the technical
      capacity for rapid MDR-TB diagnosis. The case report underscores an urgent need
      to explore the use of WHO-endorsed techniques such as Xpert MTB/Rif and
      commercial assays such as Genotype MTBDR for rapid diagnosis of MDR-TB among new
      cases. Suitable applications may be found for other TB high-burden countries
      where MDR-TB is a major concern. 

PMID- 25956027
TI  - Binding of calmodulin changes the calcineurin regulatory region to a less dynamic
      conformation.
AB  - Calcineurin (CN) is a Ca(2+)/calmodulin (CaM) activated serine/threonine
      phosphatase, and its regulatory region (CNRR) plays a critical role in the
      coupling of Ca(2+) signals to cellular responses. Ca(2+)/CaM binds to the CNRR,
      resulting in a conformational change that removes an autoinhibitory domain (CN467
      486) from the active site of the phosphatase and activates the enzyme. However,
      almost the entire regulatory region (CN374-521) is not visible in the electron
      density maps of reported structures. In this study, we produced separate CN
      fragments corresponding to the CNRR (CNRR381-521, CN residues 381-521) and
      determined the binding affinity of CNRR381-521 for Ca(2+)/CaM using isothermal
      titration calorimetry (ITC). The structural change in CNRR381-521 induced by
      Ca(2+)/CaM binding was also investigated by Fourier transform infrared
      spectroscopy (FT-IR). The results indicate that Ca(2+)/CaM binding to CNRR381-521
      is an exothermic reaction with a dissociation constant of 2.0*10(-6) M. Binding
      of calmodulin changes the calcineurin regulatory region to a less dynamic
      conformation.

PMID- 25956029
TI  - The Nucleolar Protein GLTSCR2 Is an Upstream Negative Regulator of the Oncogenic
      Nucleophosmin-MYC Axis.
AB  - The transcriptional factor MYC and the nucleophosphoprotein nucleophosmin (NPM)
      act in concert to regulate the proliferation of both normal and cancer cells. MYC
      directly interacts with NPM to form an NPM-MYC binary complex, which is recruited
      to the promoter of MYC target genes to induce the transcription of proteins
      required for transformation, thus forming an oncogenic NPM-MYC axis. However, the
      regulatory molecules and mechanisms that control the transcription of MYC target
      genes by NPM remain to be determined. Herein, we describe a novel function of the
      nucleolar protein glioblastoma tumor-suppressive candidate region gene 2
      (GLTSCR2) in regulating the transcriptional activity of MYC through an NPM
      dependent pathway in SK-BR3 breast cancer cells. GLTSCR2 bound to NPM weakly in
      the nucleolus, but the redistribution of GLTSCR2 to the nucleoplasm increased the
      binding affinity between the two proteins. Enhancing the GLTSCR2-NPM interaction
      competitively inhibited the formation of the NPM-MYC binary complex, resulting in
      a decrease in the recruitment of the NPM-MYC complex to the MYC target gene
      promoter. This process suppressed the transcriptional and transformational
      activities of MYC. Thus, our data demonstrated that GLTSCR2 was an upstream
      negative regulator of the NPM-MYC axis involved in controlling the
      transcriptional activity of MYC, thereby suggesting that GLTSCR2 may be a novel
      candidate molecule for suppressing the growth of cancer cells stimulated by MYC
      hyperactivation. 

PMID- 25956028
TI  - Multiple Mechanisms of Unfolded Protein Response-Induced Cell Death.
AB  - Eukaryotic cells fold and assemble membrane and secreted proteins in the
      endoplasmic reticulum (ER), before delivery to other cellular compartments or the
      extracellular environment. Correctly folded proteins are released from the ER,
      and poorly folded proteins are retained until they achieve stable conformations;
      irreparably misfolded proteins are targeted for degradation. Diverse pathological
      insults, such as amino acid mutations, hypoxia, or infection, can overwhelm ER
      protein quality control, leading to misfolded protein buildup, causing ER stress.
      To cope with ER stress, eukaryotic cells activate the unfolded protein response
      (UPR) by increasing levels of ER protein-folding enzymes and chaperones,
      enhancing the degradation of misfolded proteins, and reducing protein
      translation. In mammalian cells, three ER transmembrane proteins, inositol
      requiring enzyme-1 (IRE1; official name ERN1), PKR-like ER kinase (PERK; official
      name EIF2AK3), and activating transcription factor-6, control the UPR. The UPR
      signaling triggers a set of prodeath programs when the cells fail to successfully
      adapt to ER stress or restore homeostasis. ER stress and UPR signaling are
      implicated in the pathogenesis of diverse diseases, including neurodegeneration,
      cancer, diabetes, and inflammation. This review discusses the current
      understanding in both adaptive and apoptotic responses as well as the molecular
      mechanisms instigating apoptosis via IRE1 and PERK signaling. We also examine how
      IRE1 and PERK signaling may be differentially used during neurodegeneration
      arising in retinitis pigmentosa and prion infection. 

PMID- 25956031
TI  - Endothelial to Mesenchymal Transition Contributes to Endothelial Dysfunction in
      Pulmonary Arterial Hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a progressive disease characterized by
      lung endothelial cell dysfunction and vascular remodeling. Normally, the
      endothelium forms an integral cellular barrier to regulate vascular homeostasis.
      During embryogenesis endothelial cells exhibit substantial plasticity that
      contribute to cardiac development by undergoing endothelial-to-mesenchymal
      transition (EndoMT). We determined the presence of EndoMT in the pulmonary
      vasculature in vivo and the functional effects on pulmonary artery endothelial
      cells (PAECs) undergoing EndoMT in vitro. Histologic assessment of patients with
      systemic sclerosis-associated PAH and the hypoxia/SU5416 mouse model identified
      the presence von Willebrand factor/alpha-smooth muscle actin-positive endothelial
      cells in up to 5% of pulmonary vessels. Induced EndoMT in PAECs by inflammatory
      cytokines IL-1beta, tumor necrosis factor alpha, and transforming growth factor
      beta led to actin cytoskeleton reorganization and the development of a
      mesenchymal morphology. Induced EndoMT cells exhibited up-regulation of
      mesenchymal markers, including collagen type I and alpha-smooth muscle actin, and
      a reduction in endothelial cell and junctional proteins, including von Willebrand
      factor, CD31, occludin, and vascular endothelial-cadherin. Induced EndoMT
      monolayers failed to form viable biological barriers and induced enhanced leak in
      co-culture with PAECs. Induced EndoMT cells secreted significantly elevated
      proinflammatory cytokines, including IL-6, IL-8, and tumor necrosis factor alpha,
      and supported higher immune transendothelial migration compared with PAECs. These
      findings suggest that EndoMT may contribute to the development of PAH.

PMID- 25956030
TI  - Monocyte Traffic, Dorsal Root Ganglion Histopathology, and Loss of Intraepidermal
      Nerve Fiber Density in SIV Peripheral Neuropathy.
AB  - HIV-associated sensory neuropathy remains the most common neurological
      complication of HIV infection and is characterized by dorsal root ganglion (DRG)
      inflammation and intraepidermal nerve fiber density (IENFD) loss. Chronic
      peripheral immune cell activation and accumulation may cause damage to the DRG,
      but has not been fully investigated yet. By using an SIV-infected, CD8-lymphocyte
      depleted rhesus macaque model, we defined immune cells surrounding DRG neurons
      and their role in DRG pathology, measured cell traffic from the bone marrow to
      the DRGs using 5-bromo-2-deoxyuridine (BrdU) pulse, and serially measured IENFD.
      We found an increase in CD68(+) and CD163(+) macrophages in DRGs of SIV-infected
      animals. MAC387(+) recently recruited monocytes/macrophages were increased, along
      with BrdU(+) cells, in the DRGs of SIV-infected macaques. We demonstrated that
      78.1% of all BrdU(+) cells in DRGs were also MAC387(+). The number of BrdU(+)
      monocytes correlated with severe DRG histopathology, which included
      neuronophagia, neuronal loss, and Nageotte nodules. These data demonstrate that
      newly recruited MAC387(+)BrdU(+) macrophages may play a significant role in DRG
      pathogenesis. IENFD decreased early (day 21), consistent with the development of
      sensory neuropathy in SIV-infected macaques. Decreased IENFD was associated with
      elevated BrdU(+) cells in the DRG. These data suggest that increased recruitment
      of macrophages to DRG is associated with severe DRG histopathology and IENFD
      loss. 

PMID- 25956033
TI  - Transcranial direct current stimulation over prefrontal cortex diminishes degree
      of risk aversion.
AB  - Previous studies have established that transcranial direct current stimulation
      (tDCS) is a powerful technique for manipulating the activity of the human
      cerebral cortex. Many studies have found that weighing the risks and benefits in
      decision-making involves a complex neural network that includes the dorsolateral
      prefrontal cortex (DLPFC). We studied whether participants change the balance of
      risky and safe responses after receiving tDCS applied over the right and left
      prefrontal cortex. A total of 60 healthy volunteers performed a risk task while
      they received either anodal tDCS over the right prefrontal cortex, with cathodal
      over the left; anodal tDCS over the left prefrontal cortex, with cathodal over
      the right; or sham stimulation. The participants tended to choose less risky
      options after receiving sham stimulation, demonstrating that the task might be
      highly influenced by the "wealth effect". There was no statistically significant
      change after either right anodal/left cathodal or left anodal/right cathodal
      tDCS, indicating that both types of tDCS impact the participants' degrees of risk
      aversion, and therefore, counteract the wealth effect. We also found gender
      differences in the participants' choices. These findings extend the notion that
      DLPFC activity is critical for risk decision-making. Application of tDCS to the
      right/left DLPFC may impact a person's attitude to taking risks. 

PMID- 25956032
TI  - Oncogenic Activity of miR-650 in Prostate Cancer Is Mediated by Suppression of
      CSR1 Expression.
AB  - Cellular stress response 1 (CSR1) is a tumor suppressor gene whose expression was
      frequently down-regulated in prostate cancer. The mechanism of its down
      regulation, however, is not clear. Here, we show that the 3' untranslated region
      of CSR1 contains a target site of miR-650. High level of miR-650 was found in
      prostate cancer samples and cell lines. Degradation of miR-650 by specific
      inhibitor dramatically increased the expression levels of CSR1. Interaction
      between miR-650 and its target site in the 3' untranslated region was validated
      through luciferase reporter system. Mutation at the target site completely
      abrogated the activity of miR-650 on the 3' untranslated region of CSR1.
      Inhibition of miR-650 reversed the expression suppression of CSR1, suppressed
      colony formation, and blocked cell cycle entry to the S phase of both PC3 and
      DU145 cells. Animal model showed significant decrease of tumor volume, rate of
      metastasis, and mortality of severe combined immunodeficient mice xenografted
      with PC3 or DU145 cells transformed with inhibitor of miR-650. Our analyses
      demonstrate that suppression of CSR1 expression is a novel mechanism critical for
      the oncogenic activity of miR-650. 

PMID- 25956034
TI  - Insulin resistance due to dietary iron overload disrupts inner hair cell ribbon
      synapse plasticity in male mice.
AB  - To evaluate whether cochlear inner hair cells (IHCs) ribbon synapse plasticity
      would be interrupted by insulin resistance (IR) due to dietary iron overload, we
      established an IR model in C57Bl/6 male mice with an iron-enriched diet for 16
      weeks. Glucose levels were measured at weeks 4, 8, 12, 16. Glucose tolerance test
      and insulin tolerance test were performed at week 16 after overnight fasting.
      Then, auditory brainstem responses (ABRs) measurements were performed for hearing
      threshold shifts. After ABR measurements, cochleae were harvested for assessment
      of the number of IHC ribbon synapses by immunostaining, the morphology of
      cochlear hair cells and spiral ganglion neurons (SGNs) by transmission electron
      microscopy or immunostaining. Here, we show that IR due to dietary iron overload
      decreased the number of ribbon synapses, and induced moderate ABR threshold
      elevations. Besides, additional components including outer hair cells (OHCs),
      IHCs, and SGNs were unaffected. Moreover, IR did not disrupt the expression of
      vesicular glutamate transporter 3 (VGLUT3), myosin VIIa and prestin in hair
      cells. These results indicate that IHC ribbon synapses may be more susceptible to
      IR due to dietary iron overload. 

PMID- 25956035
TI  - Interaction of (12)C ions with the mouse retinal response to light.
AB  - Astronauts in orbit reported phosphenes varying in shape and orientation across
      the visual field; incidence was correlated with the radiation flux. Patients with
      skull tumors treated by (12)C ions and volunteers whose posterior portion of the
      eye was exposed to highly ionizing particles in early studies reported comparable
      percepts. An origin in radiation activating the visual system is suggested.
      Bursts (~ 4 ms) of (12)C ions evoked electrophysiological mass responses
      comparable to those to light in the retina of anesthetized wild-type mice at
      threshold flux intensities consistent with the incidence observed in humans. The
      retinal response amplitude increased in mice with ion intensity to a maximum at ~
      2000 ions/burst, to decline at higher intensities; the inverted-U relationship
      suggests complex effects on retinal structures. Here, we show that bursts of
      (12)C ions presented simultaneously to white light stimuli reduced the
      presynaptic mass response to light in the mouse retina, while increasing the
      postsynaptic retinal and cortical responses amplitude and the phase-locking to
      stimulus of cortical low frequency and gamma (~ 25-45 Hz) responses. These
      findings suggest (12)C ions to interfere with, rather than mimicking the light
      action on photoreceptors; a parallel action on other retinal
      structures/mechanisms resulting in cortical activation is conceivable.
      Electrophysiological visual testing appears applicable to monitor the radiation
      effects and in designing countermeasures to prevent functional visual impairment
      during operations in space.

PMID- 25956036
TI  - Meeting the challenges of measuring human immune regulation.
AB  - Data is now emerging that many human diseases not previously considered immune
      diseases have an immunological basis. As such human immunology is in need of more
      standardized systems-wide methods for monitoring immune regulation. Despite
      significant advances in basic immunology research, thousands of patients visiting
      health practitioners daily still have no reliable immunological metrics by which
      to assess the status of their immune health beyond the standard blood count.
      Further investigations are costly, time consuming and often don't offer
      significant insights into the mechanics of immune deviation or regulation. The
      immune system meets many criteria of complex biological networks and therefore
      systems-wide approaches are highly suitable to determining the emergent
      properties of immune responses. Standardization of immune monitoring, the
      development of new technology and integrated informatics approaches are needed in
      order to identify useful hematological and serological markers that are
      informative for immune health. This brief review outlines some of the more
      promising developments in systems immunology. 

PMID- 25956037
TI  - A signaling-enhanced chimeric receptor to activate the ICOS pathway in T cells.
AB  - Activation of the inducible costimulator (ICOS) signaling pathway in T cells is
      difficult to assess with bioassays, because most T cell lines do not
      constitutively express ICOS. Additionally, engagement of ICOS by its natural
      ligand B7 related protein 1 (B7RP1) is insufficient to elicit ICOS signaling, but
      requires simultaneous costimulation of the T cell receptor (TCR) to be effective.
      Here we describe a genetically engineered human T cell line that expresses a
      chimeric receptor (ICOS-CD3) consisting of full-length human ICOS fused at its C
      terminal end to the cytoplasmic domain of human CD3 zeta. When engaged by B7RP1,
      ICOS-CD3 initiated signaling independently of TCR costimulation and induced
      substantially more IL-2 secretion in Jurkat T cells compared to wildtype ICOS. We
      demonstrate that this signaling-enhanced chimeric receptor can be used in simple
      and sensitive bioassays to detect bioactive B7RP1, anti-B7RP1 drugs, and the
      presence of corresponding neutralizing anti-drug antibodies. 

PMID- 25956038
TI  - For3D: Full organ reconstruction in 3D, an automatized tool for deciphering the
      complexity of lymphoid organs.
AB  - To decipher the complex topology of lymphoid structures, we developed an
      automated process called Full Organ Reconstruction in 3D (For3D). A dedicated
      image-processing pipeline is applied to entire collections of immunolabeled
      serial sections, acquired with a slide-scanning microscope. This method is
      automated, flexible and readily applicable in two days to frozen or paraffin
      embedded organs stained by fluorescence or brightfield immunohistochemistry. 3D
      reconstructed organs can be visualized, rotated and analyzed to quantify
      substructures of interest. Usefulness of For3D is exemplified here through
      topological analysis of several mouse lymphoid organs exhibiting a complex
      organization: (i) the thymus, composed of two compartments, a medulla intricately
      imbricated into a surrounding cortex, (ii) lymph nodes, also highly
      compartmentalized into cortex, paracortex and medulla and (iii) the
      vascularization of an EG7 primary thymoma. This open-source algorithm, based on
      ImageJ and Matlab scripts, offers a user-friendly interface and is widely
      applicable to any organ or tissue, hence readily adaptable to a broad range of
      biomedical samples. 

PMID- 25956039
TI  - Phyllodes tumour with heterologous sarcomatous differentiation: Case series with
      literature review.
AB  - INTRODUCTION: Phyllodes tumours are rare fibroepithelial malignancies of the
      breast, accounting for less than 1% of malignant breast tumours. Further
      malignant differentiation of phyllodes tumours can occur, resulting in cases of
      extremely rare heterologous sarcomatous differentiation. PRESENTATION OF CASE:
      Two females in their fifties were diagnosed with malignant phyllodes tumour
      associated with heterologous sarcomatous differentiation. The first patient, aged
      50 had phyllodes tumour with chondrosarcoma, osteosarcoma and ductal carcinoma-in
      situ. The second patient, aged 53 had phyllodes tumour with osteosarcoma and
      liposarcoma. DISCUSSION: The association of phyllodes tumour and heterologous
      sarcomatous differentiation is rare, with only 4 previously reported cases in
      English literature. The paucity of evidence presents challenges in its management
      with uncertain prognosis and monitoring requirements for two aforementioned
      patients. CONCLUSION: Further case series and long-term follow up is required for
      accurate characterisation of phyllodes tumours with heterologous sarcomatous
      differentiation.

PMID- 25956040
TI  - Innominate vein repair after iatrogenic perforation with central venous catheter
      via mini-sternotomy-Case report.
AB  - INTRODUCTION: Iatrogenic damage of the innominate vein is a possible complication
      with extracorporeal central venous line catheter insertion techniques. When
      perforation occurs, the catheter is left in place and surgery is required for
      careful removal and repair of other possible complications, including hemothorax
      and cardiac tamponade. The traditional approach for innominate vein repair is via
      a complete median sternotomy. PRESENTATION OF CASE: A 75-year-old female patient
      with hypertension, diabetes mellitus type two and end stage renal failure,
      coronary artery disease presenting with iatrogenic innominate vein perforation
      and pulmonary effusion status post placement of a tunneled hemodialysis catheter
      through the left subclavian vein. DISCUSSION: The patient underwent a partial
      upper sternotomy into the right fourth intercostal space. Ministernotomy and
      endovascular techniques provide similar outcomes to those of traditional surgical
      approaches. However, with minimal access and trauma, these new methods provide
      better post-operative outcomes for patients. CONCLUSION: The case presented in
      this report suggests a new approach to replace the traditional complete median
      sternotomy in attempts to repair the innominate vein. The mini-sternotomy
      approach provides sufficient visualization of the vessel and surrounding
      structures with minimal post-operative complications and healing time.

PMID- 25956041
TI  - The role of T-cell phenotype and T-cell receptor rearrangement in the diagnosis
      of T-cell malignancies.

PMID- 25956043
TI  - Flow cytometry as a diagnostic support tool in juvenile myelomonocytic leukemia.

PMID- 25956042
TI  - A randomized, phase 2 study of R-CHOP plus enzastaurin vs R-CHOP in patients with
      intermediate- or high-risk diffuse large B-cell lymphoma.

PMID- 25956044
TI  - Primary mediastinal large B-cell lymphoma in pregnancy.

PMID- 25956045
TI  - SET-NUP214 rearrangement in isolation is insufficient to induce leukemia: a
      single center experience.

PMID- 25956046
TI  - Minimal residual disease after long-term interferon-alpha2 treatment: a report on
      hematological, molecular and histomorphological response patterns in 10 patients
      with essential thrombocythemia and polycythemia vera.
AB  - Essential thrombocythemia (ET) and polycythemia vera (PV) are Philadelphia
      chromosome-negative chronic myeloproliferative neoplasms (MPNs) characterized by
      the JAK2 V617F mutation, which can be found in more than 98% of PV patients and
      in ~ 50% of ET patients. Assessment of the JAK2 V617F allele burden by a highly
      sensitive quantitative PCR (qPCR) assay appears to be a useful tool for
      monitoring minimal residual disease (MRD) and evaluating treatment efficacy. This
      report expands and substantiates existing data, showing that IFN-alpha2 is a
      highly potent immunomodulating agent capable of inducing MRD with low-burden JAK2
      V617F, major molecular response (MMR), complete hematological remission (CHR) and
      complete histomorphological normalization of the bone marrow in a sub-set of
      patients with ET and PV after long-term treatment (>= 3.5 years). Furthermore,
      long-lasting hematological, molecular and histomorphological remissions are
      sustained after discontinuation of IFN-alpha2 for up to ~ 5-6 years.

PMID- 25956047
TI  - Floating tablets for controlled release of ofloxacin via compression coating of
      hydroxypropyl cellulose combined with effervescent agent.
AB  - To prolong the residence time of dosage forms within gastrointestinal trace until
      all drug released at desired rate was one of the real challenges for oral
      controlled-release drug delivery system. Herein, we developed a fine floating
      tablet via compression coating of hydrophilic polymer (hydroxypropyl cellulose)
      combined with effervescent agent (sodium bicarbonate) to achieve simultaneous
      control of release rate and location of ofloxacin. Sodium alginate was also added
      in the coating layer to regulate the drug release rate. The effects of the weight
      ratio of drug and the viscosity of HPC on the release profile were investigated.
      The optimized formulations were found to immediately float within 30s and remain
      lastingly buoyant over a period of 12 h in simulated gastric fluid (SGF, pH 1.2)
      without pepsin, indicating a satisfactory floating and zero-order drug release
      profile. In addition, the oral bioavailability experiment in New Zealand rabbits
      showed that, the relative bioavailability of the ofloxacin after administrated of
      floating tablets was 172.19%, compared to marketed common release tablets
      TaiLiBiTuo((r)). These results demonstrated that those controlled-released
      floating tables would be a promising gastro-retentive delivery system for drugs
      acting in stomach.

PMID- 25956048
TI  - Functional peptide nanocarriers for delivery of novel anti-RelA RNA interference
      agents as a topical treatment of atopic dermatitis.
AB  - Small interfering RNAs (siRNAs) are a potential treatment of atopic dermatitis
      (AD) because they can specifically silence the gene expression of AD-related
      factors. However, siRNA alone cannot exert a sufficiently strong therapeutic
      effect due to low delivery efficiency to the target tissues and cells; simply
      increasing the amount used is not possible due to the possibility of off-target
      effects. We previously reported a novel class of therapeutic RNA interference
      (RNAi) agents called nkRNA((r)) and PnkRNA((r)), which have been shown to be
      effective in several disease models, have greater resistance to nuclease
      degradation than canonical siRNAs, and do not induce any immunotoxicity. In the
      present study, we describe a non-invasive and effective transdermal RNAi
      therapeutic system for atopic dermatitis that uses the functional cell
      penetrating stearoyl-oligopeptide OK-102 as a cytoplasm-responsive nanocarrier
      for nkRNA((r)) and PnkRNA((r)). The two RNAi agents were targeted against RelA, a
      subclass of NF-kappaB (nuclear factor kappa B), and, as part of OK-102 complexes,
      they strongly silenced RelA mRNA in macrophage cells and demonstrated a
      significant therapeutic effect in a mouse model of AD. It was shown that OK-102
      complexed RNAi agents were an efficient therapeutic system for AD and caused no
      adverse reactions. 

PMID- 25956049
TI  - Comparison of the oral bioavailability of silymarin-loaded lipid nanoparticles
      with their artificial lipolysate counterparts: implications on the contribution
      of integral structure.
AB  - Both solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs)
      were artificially broken down into lipolysates. Their oral bioavailability, with
      silymarin as a model drug, was compared in dogs to highlight the contribution of
      their integral structure. The lipid nanoparticles were prepared using a
      conventional hot homogenization method, whereas the lipolysates were obtained
      through lipolysis in phospholipid- and bile salt-enriched simulated intestinal
      fluid. More than 80% of vehicle-associated drugs could be transformed into the
      water-soluble form of mixed micelles. Pharmacokinetics analysis in dogs showed a
      decrease in bioavailability of 74.86% and 59.09% for lipolysates compared to
      integral NLCs and SLNs, respectively. It was indicated that lipolysates
      contributed to a majority of drug absorption. Integral nanoparticles were
      superior to their lipolysate counterparts, but only marginally; if the
      approximately 20% of the drug that precipitated during in vitro lipolysis was
      deducted from the overall absorption amount, the superiority of integral
      nanoparticles would be significantly compromised. In conclusion, lipolysis was
      the predominant in vivo absorption mechanism, and the contribution of intact
      lipid nanoparticles was limited. 

PMID- 25956050
TI  - Multifunctional mesoporous silica nanoparticles mediated co-delivery of
      paclitaxel and tetrandrine for overcoming multidrug resistance.
AB  - The objective of the study is to fabricate multifunctional mesoporous silica
      nanoparticles for achieving co-delivery of conventional antitumor drug paclitaxel
      (PTX) and the multidrug resistance reversal agent tetrandrine (TET) expecting to
      overcome multidrug resistance of MCF-7/ADR cells. The nanoparticles were facile
      to prepare by self-assemble in situ drug loading approach. Namely, PTX and TET
      were solubilized in the cetyltrimethylammonium bromide (CTAB) micelles and
      simultaneously silica resources hydrolyze and condense to form nanoparticles. The
      obtained nanoparticles, denoted as PTX/TET-CTAB@MSN, exhibited pH-responsive
      release property with more easily released in the weak acidic environment.
      Studies on cellular uptake of nanoparticles demonstrated TET could markedly
      increase intracellular accumulation of nanoparticles. Furthermore, the PTX/TET
      CTAB@MSN suppressed tumor cells growth more efficiently than only delivery of PTX
      (PTX-CTAB@MSN) or the free PTX. Moreover, the nanoparticle loading drugs with a
      PTX/TET molar ratio of 4.4:1 completely reversed the resistance of MCF-7/ADR
      cells to PTX and the resistance reversion index was 72.3. Mechanism research
      showed that both TET and CTAB could arrest MCF-7/ADR cells at G1 phase; and
      besides PTX arrested cells at G2 phase. This nanocarrier might have important
      potential in clinical implications for co-delivery of multiple drugs to overcome
      MDR. 

PMID- 25956051
TI  - Hyaluronic acid based micelle for articular delivery of triamcinolone,
      preparation, in vitro and in vivo evaluation.
AB  - A novel triamcinolone loaded polymeric micelle was synthesized based on
      hyaluronic acid and phospholipid for articular delivery. The newly developed
      micelle was characterized for physicochemical properties including size, zeta
      potential, differential scanning calorimetry (DSC) analysis and also morphology
      by means of transmission electron microscopy. The biocompatibility of micelle was
      explored by histopathological experiment in rat model. Also biological fate of
      micelle was investigated in rat by means of real time in vivo imaging system.
      Triamcinolone loaded micelle was in the size range of 186 nm with negative zeta
      potential charge. Micelles were spherical in shape with core shell like
      structure. Triamcinolone was released from micelle during 76 h with almost low
      burst effect. DSC analysis showed the conversion of crystalline triamcinolone
      from its crystalline state. Histopathological analysis showed no evidence of
      tissue damage or phagocytic accumulation in knee joint of rat. The real time in
      vivo imaging analysis suggested at least three days retention time of micellar
      system in knee joint post injection.

PMID- 25956053
TI  - Alteration of the P-wave non-linear dynamics near the onset of paroxysmal atrial
      fibrillation.
AB  - The analysis of P-wave variability from the electrocardiogram (ECG) has been
      suggested as an early predictor of the onset of paroxysmal atrial fibrillation
      (PAF). Hence, a preventive treatment could be used to avoid the loss of normal
      sinus rhythm, thus minimising health risks and improving the patient's quality of
      life. In these previous studies the variability of different temporal and
      morphological P-wave features has been only analysed in a linear fashion.
      However, the electrophysiological alteration occurring in the atria before the
      onset of PAF has to be considered as an inherently complex, chaotic and non
      stationary process. This work analyses the presence of non-linear dynamics in the
      P-wave progression before the onset of PAF through the application of the central
      tendency measure (CTM), which is a non-linear metric summarising the degree of
      variability in a time series. Two hour-length ECG intervals just before the
      arrhythmia onset belonging to 46 different PAF patients were analysed. In
      agreement with the invasively observed inhomogeneous atrial conduction preceding
      the onset of PAF, CTM for all the considered P-wave features showed higher
      variability when the arrhythmia was closer to its onset. A diagnostic accuracy
      around 80% to discern between ECG segments far from PAF and close to PAF was
      obtained with the CTM of the metrics considered. This result was similar to
      previous P-wave variability methods based on linear approaches. However, the
      combination of linear and non-linear methods with a decision tree improved
      considerably their discriminant ability up to 90%, thus suggesting that both
      dynamics could coexist at the same time in the fragmented depolarisation of the
      atria preceding the arrhythmia. 

PMID- 25956055
TI  - Twenty weeks of home-based interactive training of children with cerebral palsy
      improves functional abilities.
AB  - BACKGROUND: Home-based training is becoming ever more important with increasing
      demands on the public health systems. We investigated whether individualized and
      supervised interactive home-based training delivered through the internet
      improves functional abilities in children with cerebral palsy (CP). METHODS:
      Thirty four children with CP (aged 9-16; mean age 10.9 +/- 2.4 years) (GMFCS I
      II; MACS I-II) were included in this non-randomized controlled clinical training
      study. 12 children (aged 7-16; mean age: 11.3+/-0.9 years) were allocated to a
      control group in which measurements were performed with 20 weeks interval without
      any intervening training. Daily activities, functional abilities of upper- and
      lower limbs, and balance were evaluated before, immediately after training and 12
      weeks after training. The training consisted of 30 min daily home-based training
      for 20 weeks delivered through the internet. RESULTS: The training group on
      average completed 17 min daily training for the 20 week period (total of 40 h of
      training). The training group showed significant improvements of daily activities
      (AMPS), upper limb function (AHA) and functional tests of lower limbs (sit to
      stand, lateral step up, half knee to standing) after 20 weeks of training. No
      difference was found between the test after 20 weeks of training and the test 12
      weeks after training. No significance was reached for balance after training. No
      difference was found for any parameter for the control group. CONCLUSIONS:
      Interactive home training of children with CP is an efficient way to deliver
      training, which can enable functional motor improvements and increased activity
      to perform daily activities. TRIAL REGISTRATION: ISRCTN13188513 . Date of
      registration: 04/12/2014.

PMID- 25956054
TI  - Accuracy of microRNAs as markers for the detection of neck lymph node metastases
      in patients with head and neck squamous cell carcinoma.
AB  - BACKGROUND: The presence of metastatic disease in cervical lymph nodes of head
      and neck squamous cell carcinoma (HNSCC) patients is a very important determinant
      in therapy choice and prognosis, with great impact in overall survival.
      Frequently, routine lymph node staging cannot detect occult metastases and the
      post-surgical histologic evaluation of resected lymph nodes is not sensitive in
      detecting small metastatic deposits. Molecular markers based on tissue-specific
      microRNA expression are alternative accurate diagnostic markers. Herein, we
      evaluated the feasibility of using the expression of microRNAs to detect
      metastatic cells in formalin-fixed paraffin-embedded (FFPE) lymph nodes and in
      fine-needle aspiration (FNA) biopsies of HNSCC patients. METHODS: An initial
      screening compared the expression of 667 microRNAs in a discovery set comprised
      by metastatic and non-metastatic lymph nodes from HNSCC patients. The most
      differentially expressed microRNAs were validated by qRT-PCR in two independent
      cohorts: i) 48 FFPE lymph node samples, and ii) 113 FNA lymph node biopsies. The
      accuracy of the markers in identifying metastatic samples was assessed through
      the analysis of sensitivity, specificity, accuracy, negative predictive value,
      positive predictive value, and area under the curve values. RESULTS: Seven
      microRNAs highly expressed in metastatic lymph nodes from the discovery set were
      validated in FFPE lymph node samples. MiR-203 and miR-205 identified all
      metastatic samples, regardless of the size of the metastatic deposit.
      Additionally, these markers also showed high accuracy when FNA samples were
      examined. CONCLUSIONS: The high accuracy of miR-203 and miR-205 warrant these
      microRNAs as diagnostic markers of neck metastases in HNSCC. These can be
      evaluated in entire lymph nodes and in FNA biopsies collected at different time
      points such as pre-treatment samples, intraoperative sentinel node biopsy, and
      during patient follow-up. These markers can be useful in a clinical setting in
      the management of HNSCC patients from initial disease staging and therapy
      planning to patient surveillance.

PMID- 25956056
TI  - Bilingual term alignment from comparable corpora in English discharge summary and
      Chinese discharge summary.
AB  - BACKGROUND: Electronic medical record (EMR) systems have become widely used
      throughout the world to improve the quality of healthcare and the efficiency of
      hospital services. A bilingual medical lexicon of Chinese and English is needed
      to meet the demand for the multi-lingual and multi-national treatment. We make
      efforts to extract a bilingual lexicon from English and Chinese discharge
      summaries with a small seed lexicon. The lexical terms can be classified into two
      categories: single-word terms (SWTs) and multi-word terms (MWTs). For SWTs, we
      use a label propagation (LP; context-based) method to extract candidates of
      translation pairs. For MWTs, which are pervasive in the medical domain, we
      propose a term alignment method, which firstly obtains translation candidates for
      each component word of a Chinese MWT, and then generates their combinations, from
      which the system selects a set of plausible translation candidates. RESULTS: We
      compare our LP method with a baseline method based on simple context-similarity.
      The LP based method outperforms the baseline with the accuracies: 4.44% Acc1,
      24.44% Acc10, and 62.22% Acc100, where AccN means the top N accuracy. The
      accuracy of the LP method drops to 5.41% Acc10 and 8.11% Acc20 for MWTs. Our
      experiments show that the method based on term alignment improves the performance
      for MWTs to 16.22% Acc10 and 27.03% Acc20. CONCLUSIONS: We constructed a
      framework for building an English-Chinese term dictionary from discharge
      summaries in the two languages. Our experiments have shown that the LP-based
      method augmented with the term alignment method will contribute to reduction of
      manual work required to compile a bilingual sydictionary of clinical terms.

PMID- 25956058
TI  - A response to a letter to the Editor: "A note on (+)-catechin" by Dr Christophe
      Wiart.

PMID- 25956057
TI  - High expression of KPNA2 defines poor prognosis in patients with upper tract
      urothelial carcinoma treated with radical nephroureterectomy.
AB  - BACKGROUND: To analyze the expression of karyopherin alpha 2 (KPNA2) in upper
      tract urothelial carcinoma (UTUC) and to investigate whether the KPNA2 expression
      provides additional prognostic information following radical nephroureterectomy
      (RNU). METHODS: A tissue microarray (TMA) containing samples from 176 patients
      with UTUC who underwent RNU at our institute was analyzed for KPNA2 expression
      using immunohistochemistry. KPNA2 expression in normal urothelial cell line and
      urothelial carcinoma cell lines was evaluated by western blot analysis. Using RNA
      interference in vitro, the effects of KPNA2 inhibition on cellular viability,
      migration and apoptosis were determined. RESULTS: KPNA2 expression was
      significantly upregulated in the UTUC samples compared with the adjacent normal
      urothelial tissues. High KPNA2 immunoreactivity was identified as a predictor of
      bladder recurrence (hazard ratio [HR]: 2.017, 95% CI 1.13-3.61, p = 0.018), poor
      disease-free survival (DFS, HR: 2.754, 95% CI 1.68-4.51, p = 0.001) and poor
      overall survival (OS, HR: 4.480, 95% CI 1.84-10.89, p = 0.001) for patients with
      UTUC after RNU. Furthermore, high KPNA2 immunoreactivity was independent of the
      conventional predictive factors in a multivariate analysis. Additional in vitro
      experiments revealed that KPNA2 expression was higher in urothelial carcinoma
      cell lines than in normal urothelial cell line. KPNA2 inhibition with a specific
      siRNA decreased cell viability and migration and increased apoptosis in
      urothelial carcinoma cell lines. CONCLUSIONS: KPNA2 is a novel independent
      prognostic marker for bladder recurrence, DFS and OS of UTUC patients who have
      undergone RNU. Moreover, these data suggest that KPNA2 may be a promising
      therapeutic target for UTUC.

PMID- 25956059
TI  - Relative dose intensity and therapy efficacy in different breast cancer molecular
      subtypes: a retrospective study of early stage breast cancer patients treated
      with neoadjuvant chemotherapy.
AB  - To investigate the relationship between chemotherapy dose intensity and therapy
      efficacy of different molecular subtypes. Clinical and pathological features of
      the patients with breast cancer were retreived from the hospital records. 315
      patients were analyzed (251 showed clinical response, 38 acquired pCR). Patients
      with positive ER status, negative PR status, higher Ki67 level and higher RTDI
      had better therapy response. 13.5 and 84.5 % were identified the benchmark of
      Ki67 and RTDI, respectively. As the result of interior-subgroup comparison,
      luminal subgroups acquired better response rate when RTDI >= 84.5 %. In patients
      of luminal breast cancer, tumor size change arose from increasing of dose
      intensity and finally showed reached a plateau after RTDI >= 95 % (r (2) = 0.303,
      p < 0.001). As the result of intersubgroup comparison, TNBC patients were more
      likely to acquired better clinical and pathology response when RDTI < 84.5 %.
      Ki67 change arose sharply from increasing of dose intensity when RDTI < 84.5 % (r
      (2) = 0.656, p < 0.001), whereas the regression curve showed a terminal plateau
      in patients of RDTI >= 84.5 % (r (2) = 0.427, p < 0.001). Given lower RTDI,
      luminal patients are less likely to achieve response, and TNBC patients are
      associated with higher response rate. Dissimilar of therapy efficacy between
      luminal subtype and TNBC becomes inconspicuous as RTDI rises. Chemosensitivity
      may associate with dose intensity, especially in luminal subtypes, and tailored
      therapeutic strategies should be considered.

PMID- 25956061
TI  - Molecular and topological membrane folding determinants of transient receptor
      potential vanilloid 2 channel.
AB  - Transient Receptor Potential (TRP) channels are related to adaptation to the
      environment and somatosensation. The transient receptor potential vanilloid
      (TRPV) subfamily includes six closely evolutionary related ion channels sharing
      the same domain organization and tetrameric arrangement in the membrane. In this
      study we have characterized biochemically TRPV2 channel membrane protein folding
      and transmembrane (TM) architecture. Deleting the first N-terminal 74 residues
      preceding the ankyrin repeat domain (ARD) show a key role for this region in
      targeting the protein to the membrane. We have demonstrated the co-translational
      insertion of the membrane-embedded region of the TRPV2 and its disposition in
      biological membranes, identifying that TM1-TM4 and TM5-TM6 regions can assemble
      as independent folding domains. The ARD is not required for TM domain insertion
      in the membrane. The folding features observed for TRPV2 may be conserved and
      shared among other TRP channels outside the TRPV subfamily. 

PMID- 25956060
TI  - In boar sperm capacitation L-lactate and succinate, but not pyruvate and citrate,
      contribute to the mitochondrial membrane potential increase as monitored via
      safranine O fluorescence.
AB  - Having ascertained using JC-1 as a probe that, in distinction with the controls,
      during capacitation boar sperm maintains high mitochondrial membrane potential
      (DeltaPsi), to gain some insight into the role of mitochondria in capacitation,
      we monitored DeltaPsi generation due to externally added metabolites either in
      hypotonically-treated spermatozoa (HTS) or in intact cells by using safranine O
      as a probe. During capacitation, the addition to HTS of L-lactate and succinate
      but not those of pyruvate, citrate and ascorbate + TMPD resulted in increase of
      DeltaPsi generation. Accordingly, the addition of L-lactate and succinate, but
      not that of citrate, to intact sperm resulted in DeltaPsi generation increased in
      capacitation.

PMID- 25956062
TI  - Overexpression of long non-coding RNA PVT1 in gastric cancer cells promotes the
      development of multidrug resistance.
AB  - BACKGROUND: The development of multidrug resistance (MDR) is a crucial problem of
      therapy failure in gastric cancer, which results in disease recurrence and
      metastasis. Plasmacytoma variant translocation 1 (PVT-1), a long non-coding RNA
      (lncRNA), was previously found to be increased in gastric cancer patients and
      regulated the chemotherapy sensitivity in pancreatic cancer cells. However, the
      role of PVT1 in multidrug resistant Gastric cancer remains largely unexplored.
      METHODS: In this study, the mRNA levels of PVT1 in gastric cancer tissues of
      cisplatin-resistant patients and two kinds of cisplatin-resistant cells
      BGC823/DDP and SGC7901/DDP were detected by qRT-PCR. The influence of PVT1
      knockdown or overexpression on anticancer drug resistance was assessed by
      measuring the cytotoxicity of cisplatin and the rate of apoptosis detected by CCK
      8 assay and flow cytometry, respectively. Further, we investigated the expression
      levels of MDR1, MRP, mTOR and HIF-1alpha by qRT-PCR and western blotting.
      RESULTS: PVT-1 was highly expressed in gastric cancer tissues of cisplatin
      resistant patients and cisplatin-resistant cells. In addition, BGC823/DDP and
      SGC7901/DDP cells transfected with PVT-1 siRNA and treated with cisplatin
      exhibited significant lower survival rate and high percentage of apoptotic tumor
      cells. While, PVT1 overexpression exhibit the anti-apoptotic property in BGC823
      and SGC7901 cells transfected with LV-PVT1-GFP and treated with cisplatin.
      Moreover, qRT-PCR and western blotting revealed that PVT1 up-regulation increased
      the expression of MDR1, MRP, mTOR and HIF-1alpha. CONCLUSIONS: Overexpression of
      LncRNA PVT1 in gastric carcinoma promotes the development of MDR, suggesting an
      efficacious target for reversing MDR in gastric cancer therapy.

PMID- 25956063
TI  - Cu/Zn superoxide dismutase and the proton ATPase Pma1p of Saccharomyces
      cerevisiae.
AB  - In eukaryotes, the Cu/Zn containing superoxide dismutase (SOD1) plays a critical
      role in oxidative stress protection as well as in signaling. We recently
      demonstrated a function for Saccharomyces cerevisiae Sod1p in signaling through
      CK1gamma casein kinases and identified the essential proton ATPase Pma1p as one
      likely target. The connection between Sod1p and Pma1p was explored further by
      testing the impact of sod1Delta mutations on cells expressing mutant alleles of
      Pma1p that alter activity and/or post-translational regulation of this ATPase. We
      report here that sod1Delta mutations are lethal when combined with the T912D
      allele of Pma1p in the C-terminal regulatory domain. This "synthetic lethality"
      was reversed by intragenic suppressor mutations in Pma1p, including an A906G
      substitution that lies within the C-terminal regulatory domain and hyper
      activates Pma1p. Surprisingly the effect of sod1Delta mutations on Pma1-T912D is
      not mediated through the Sod1p signaling pathway involving the CK1gamma casein
      kinases. Rather, Sod1p sustains life of cells expressing Pma1-T912D through
      oxidative stress protection. The synthetic lethality of sod1Delta Pma1-T912D
      cells is suppressed by growing cells under low oxygen conditions or by treatments
      with manganese-based antioxidants. We now propose a model in which Sod1p
      maximizes Pma1p activity in two ways: one involving signaling through CK1gamma
      casein kinases and an independent role for Sod1p in oxidative stress protection. 

PMID- 25956064
TI  - Salvianolic acid B accelerated ABCA1-dependent cholesterol efflux by targeting
      PPAR-gamma and LXRalpha.
AB  - OBJECTIVES: Cholesterol efflux has been thought to be the main and basic
      mechanism by which free cholesterol is transferred from extra hepatic cells to
      the liver or intestine for excretion. Salvianolic acid B (Sal B) has been widely
      used for the prevention and treatment of atherosclerotic diseases. Here, we
      sought to investigate the effects of Sal B on the cholesterol efflux in THP-1
      macrophages. METHODS: After PMA-stimulated THP-1 cells were exposed to 50 mg/L of
      oxLDL and [(3)H] cholesterol (1.0 MUCi/mL) for another 24 h, the effect of Sal B
      on cholesterol efflux was evaluated in the presence of apoA-1, HDL2 or HDL3. The
      expression of ATP binding cassette transporter A1 (ABCA1), peroxisome
      proliferator-activated receptor-gamma (PPAR-gamma), and liver X receptor-alpha
      (LXRalpha) was detected both at protein and mRNA levels in THP-1 cells after the
      stimulation of Sal B. Meanwhile, specific inhibition of PPAR-gamma and LXRalpha
      were performed to investigate the mechanism. RESULTS: The results showed that Sal
      B significantly accelerated apoA-I- and HDL-mediated cholesterol efflux in both
      dose- and time-dependent manners. Meanwhile, Sal B treatment also enhanced the
      expression of ABCA1 at both mRNA and protein levels. Then the data demonstrated
      that Sal B increased the expression of PPAR-gamma and LXRalpha. And the
      application of specific agonists and inhibitors of further confirmed that Sal
      exert the function through PPAR-gamma and LXRalpha. CONCLUSION: These results
      demonstrate that Sal B promotes cholesterol efflux in THP-1 macrophages through
      ABCA1/PPAR-gamma/LXRalpha pathway.

PMID- 25956065
TI  - 2,2,2-Trichloroethanol lengthens the circadian period of Bmal1-driven circadian
      bioluminescence rhythms in U2OS cells.
AB  - 2,2,2-Trichloroethanol (TCOH) is responsible for the pharmacological actions of
      chloral hydrate (CH), and is a major metabolite of trichloroethylene. Human
      exposure to TCOH is known to be increasing. Recently, it was reported that TCOH
      causes a significant phase delay of Per2 expression in mouse liver when injected
      daily over the course of several days. However, it is not clear whether TCOH
      directly modulates the molecular clock. In the present study we used a cell-based
      assay system to test this possibility. We found that the daily oscillation period
      of Bmal1 was lengthened to 3 h following treatment with 1.5 mM TCOH, and
      increased to 5 h with 3 mM TCOH treatment. However, low concentrations of TCOH
      had no noticeable effects. The effect of TCOH on Per2 oscillation was marginal.
      Interestingly, serum from rats anesthetized with CH also modulated Bmal1 period,
      suggesting that exposure to anesthesia should be taken into consideration for
      circadian rhythm studies. In summary, our study reveals a direct regulation of
      TCOH on molecular clock. 

PMID- 25956067
TI  - Asymptomatic heterotopic pancreas in Meckel's diverticulum: a case report and
      review of the literature.
AB  - INTRODUCTION: Heterotopic pancreas is defined as pancreatic tissue without a real
      anatomical or vascular connection to the pancreas. It can be found in the
      stomach, duodenum, jejunum, ileum, Meckel's diverticulum, colon gall bladder,
      umbilicus, fallopian tube, mediastinum, spleen and liver. Complications of
      heterotopic pancreas are inflammation, bleeding, obstruction, malignant
      transformation, carcinoid syndrome, jejunojejunal intussusception and ileus, but
      it is usually asymptomatic and diagnosed only during examinations for other
      diseases. CASE PRESENTATION: An 81-year-old Lithuanian woman was diagnosed with
      caecal cancer and had undergone elective surgery. A right hemicolectomy was
      performed and a Meckel's diverticulum was observed and excised. Histological
      results showed a poorly differentiated G3 adenocarcinoma of her large intestine
      and heterotopic pancreas tissue in the Meckel's diverticulum and mesenteric
      adipose tissue. CONCLUSIONS: Asymptomatic heterotopic pancreas is rarely
      diagnosed, and usually found incidentally during surgical or diagnostic
      interventions. Although it has no symptoms, heterotopic pancreas found during
      surgical procedures should be excised.

PMID- 25956066
TI  - Inhibition of the proliferation and acceleration of migration of vascular
      endothelial cells by increased cysteine-rich motor neuron 1.
AB  - Cysteine-rich motor neuron 1 (CRIM1) is upregulated only in extracellular matrix
      gels by angiogenic factors such as vascular endothelial growth factor (VEGF). It
      then plays a critical role in the tube formation of endothelial cells. In the
      present study, we investigated the effects of increased CRIM1 on other
      endothelial functions such as proliferation and migration. Knock down of CRIM1
      had no effect on VEGF-induced proliferation or migration of human umbilical vein
      endothelial cells (HUVECs), indicating that basal CRIM1 is not involved in the
      proliferation or migration of endothelial cells. Stable CRIM1-overexpressing
      endothelial F-2 cells, termed CR1 and CR2, were constructed, because it was
      difficult to prepare monolayer HUVECs that expressed high levels of CRIM1.
      Proliferation was reduced and migration was accelerated in both CR1 and CR2
      cells, compared with normal F-2 cells. Furthermore, the transient overexpression
      of CRIM1 resulted in decreased proliferation and increased migration of bovine
      aortic endothelial cells. In contrast, neither proliferation nor migration of COS
      7 cells were changed by the overexpression of CRIM1. These results demonstrate
      that increased CRIM1 reduces the proliferation and accelerates the migration of
      endothelial cells. These CRIM1 effects might contribute to tube formation of
      endothelial cells. CRIM1 induced by angiogenic factors may serve as a regulator
      in endothelial cells to switch from proliferating cells to morphological
      differentiation. 

PMID- 25956068
TI  - Clinicopathological review of 156 appendicectomies for acute appendicitis in
      children in Ile-Ife, Nigeria: a retrospective analysis.
AB  - BACKGROUND: Acute appendicitis is one of the most common causes of acute abdomen
      in children. Late surgical intervention is often associated with increase
      morbidity and sometimes fatal outcome. We sought to determine the pattern of
      presentation of acute appendicitis, and the effect of late presentation on
      surgical outcome in children. METHODS: This is a retrospective descriptive study
      done at the paediatric surgical unit of Obafemi Awolowo University Teaching
      Hospitals Complex, Ile-Ife, Nigeria. The hospital records of all 180 patients (15
      years and below) treated for acute appendicitis, between January 1995 and
      December 2012, were reviewed; only 156 patients had adequate records out of which
      139 cases confirmed histologically as having appendicitis were analyzed. RESULTS:
      There were 80 (57.6%) females and 59 (42.4%) males. The age range was 5-15 years
      with mean (SD) age of 11.2 (+/-2.9) years. Most patients (64.7%) were more than
      10 years old. Sixty-four (46%) patients had simple appendicitis while 75 (54%)
      patients had complicated appendicitis. More children with complicated
      appendicitis (63, 84.0%) presented after 24 hours of abdominal pain; and they had
      more vomiting (59, 78.7%), spent longer days on admission (57, 76.0%) and had
      more post- operative complications (34, 45.3%) compared with uncomplicated
      appendicitis (25, 39.1%; 29, 45.3%; 7, 10.9%; 1, 1.6% respectively), and this was
      statistically significant (p < 0.05). No mortality was recorded among these
      children. CONCLUSION: Late presentation was common and was associated with longer
      duration of hospital stay and high morbidity. No mortality was recorded from the
      disease.

PMID- 25956069
TI  - The psychometric properties of Observer OPTION(5), an observer measure of shared
      decision making.
AB  - OBJECTIVES: Observer OPTION(5) was designed as a more efficient version of
      OPTION(12), the most commonly used measure of shared decision making (SDM). The
      current paper assesses the psychometric properties of OPTION(5). METHODS: Two
      raters used OPTION(5) to rate recordings of clinical encounters from two previous
      patient decision aid (PDA) trials (n=201; n=110). A subsample was re-rated two
      weeks later. We assessed discriminative validity, inter-rater reliability, intra
      rater reliability, and concurrent validity. RESULTS: OPTION(5) demonstrated
      discriminative validity, with increases in SDM between usual care and PDA arms.
      OPTION(5) also demonstrated concurrent validity with OPTION(12), r=0.61 (95%CI
      0.54, 0.68) and intra-rater reliability, r=0.93 (0.83, 0.97). The mean difference
      in rater score was 8.89 (95% Credibility Interval, 7.5, 10.3), with intraclass
      correlation (ICC) of 0.67 (95% Credibility Interval, 0.51, 0.91) for the accuracy
      of rater scores and 0.70 (95% Credibility Interval, 0.56, 0.94) for the
      consistency of rater scores across encounters, indicating good inter-rater
      reliability. Raters reported lower cognitive burden when using OPTION(5) compared
      to OPTION(12). CONCLUSIONS: OPTION(5) is a brief, theoretically grounded observer
      measure of SDM with promising psychometric properties in this sample and low
      burden on raters. PRACTICE IMPLICATIONS: OPTION(5) has potential to provide
      reliable, valid assessment of SDM in clinical encounters.

PMID- 25956070
TI  - Functional, interactive and critical health literacy: Varying relationships with
      control over care and number of GP visits.
AB  - OBJECTIVE: The aim of this study is to examine the extent to which functional,
      interactive and critical health literacy are associated with patients' perceived
      control over care and frequency of GP visits. METHODS: Data from the Dutch
      'National Panel of People with Chronic Illness or Disability' was used (N=2508).
      Health literacy was assessed by the Functional, Communicative and Critical Health
      Literacy measure. Perceived control over care was indicated by perceived ability
      to organize care, interact with providers and to perform self-care. By
      multivariate linear and logistic regression analyses, associations between health
      literacy and perceived control over care and subsequently frequency of GP visits
      were studied. RESULTS: Mainly interactive health literacy was associated with
      patients' perceived ability to organize care, interact with healthcare providers
      and perform self-care, whereas only functional health literacy was associated
      with number of GP visits. CONCLUSION: The results imply that some patients' may
      be less able to exert control over their care because of lower health literacy.
      Functional, interactive and critical health literacy vary in their relevance for
      patients' ability to exert control. PRACTICE IMPLICATIONS: Initiatives for
      strengthening patients' role in healthcare may be improved by paying attention to
      patients' health literacy, specifically functional and interactive health
      literacy.

PMID- 25956071
TI  - gamma-Tocotrienol reduces human airway smooth muscle cell proliferation and
      migration.
AB  - AIMS: Vitamin E is an antioxidant that occurs in 8 different forms (alpha, beta,
      gamma, and delta tocopherol and tocotrienol). Clinical trials of tocopherol
      supplementation to assess the impact of antioxidant activity in asthma have
      yielded equivocal results. Tocotrienol exhibits greater antioxidant activity than
      tocopherol in several biological phenomena in vivo and in vitro. We tested the
      effect of tocotrienol on human airway smooth muscle (ASM) cell growth and
      migration, both of which mediate airway remodeling in asthma. MAIN METHODS: We
      measured platelet-derived growth factor-BB (PDGF-BB)-induced ASM cell
      proliferation and migration by colorimetric and Transwell migration assays in the
      presence and absence of gamma-tocotrienol (an isoform of tocotrienol). KEY
      FINDINGS: PDGF-BB-induced ASM cell proliferation and migration were inhibited by
      gamma-tocotrienol. This effect was associated with inhibition of RhoA activation,
      but it had no effect on p42/p44 mitogen-activated protein kinase (MAPK) or Akt1
      activation. We confirmed that pharmacological inhibition of Rho kinase activity
      was sufficient to inhibit PDGF-BB-induced ASM cell proliferation and migration.
      SIGNIFICANCE: gamma-Tocotrienol could impart therapeutic benefits for airway
      remodeling in asthma by inhibiting human ASM cell proliferation and migration.

PMID- 25956074
TI  - (99m)Tc-amitrole as a novel selective imaging probe for solid tumor: In silico
      and preclinical pharmacological study.
AB  - Lactoperoxidase (LPO) inhibitors are very selective for solid tumor due to their
      high binding affinity to the LPO enzyme. A computational study was used to select
      top-ranked LPO inhibitor (alone and in complex with (99m)Tc) with high in silico
      affinity. The novel prepared (99m)Tc-amitrole complex demonstrated both in silico
      and in vivo high affinity toward solid tumors.(99m)Tc-amitrole was radio
      synthesized with a high radiochemical yield (89.7+/-3.25). It showed in vitro
      stability for up to 6h. Its preclinical evaluation in solid tumor-bearing mice
      showed high retention and biological accumulation in solid tumor cells with a
      high Target/Non-Target (T/NT) ratio equal to 4.9 at 60min post-injection. The
      data described previously could recommend (99m)Tc-amitrole as potential targeting
      scintigraphic probe for solid tumor imaging. 

PMID- 25956072
TI  - The 24-h lung-function profile of once-daily tiotropium and olodaterol fixed-dose
      combination in chronic obstructive pulmonary disease.
AB  - BACKGROUND: This study investigated the effects on 24-h lung function and lung
      volume of a once-daily fixed-dose combination (FDC) of the long-acting muscarinic
      antagonist tiotropium and the long-acting beta2-agonist olodaterol in patients
      with chronic obstructive pulmonary disease. METHODS: This was a randomised,
      double-blind, placebo-controlled, Phase III trial with an incomplete crossover
      design. Patients received four of the following six treatment options for 6 weeks
      each: placebo, olodaterol 5 MUg, tiotropium 2.5 MUg, tiotropium 5 MUg, tiotropium
      + olodaterol FDC 2.5/5 MUg and tiotropium + olodaterol FDC 5/5 MUg, all delivered
      via the Respimat((r)) inhaler. The primary end point was forced expiratory volume
      in 1 s (FEV1) area under the curve from 0 to 24 h (AUC0-24) response after 6
      weeks of treatment; key secondary end points were FEV1 AUC from 0 to 12 h and AUC
      from 12 to 24 h, and further end points included lung-volume parameters measured
      using body plethysmography (subset of patients), measures of peak and trough
      FEV1, and incidence of adverse events. RESULTS: A significant improvement in FEV1
      AUC0-24 response was observed with tiotropium + olodaterol 5/5 MUg and 2.5/5 MUg
      versus placebo and monotherapies after 6 weeks of treatment; mean response with
      tiotropium + olodaterol 5/5 MUg versus placebo was 0.280 L (p < 0.0001).
      Differences to monotherapies with tiotropium + olodaterol 5/5 MUg were 0.115 L
      versus olodaterol 5 MUg, 0.127 L versus tiotropium 2.5 MUg and 0.110 L versus
      tiotropium 5 MUg (p < 0.0001 for all comparisons). Secondary end points supported
      these data. No safety concerns were identified. CONCLUSIONS: Overall, this study
      demonstrated improvements in lung function over 24 h with an FDC of tiotropium +
      olodaterol over tiotropium or olodaterol alone, with no observed difference in
      tolerability. ClinicalTrials.gov number: NCT01559116.

PMID- 25956073
TI  - The risk and outcomes of pneumonia in patients on inhaled corticosteroids.
AB  - Corticosteroids are frequently prescribed anti-inflammatory medications. Inhaled
      corticosteroids (ICS) are indicated for Chronic Obstructive Pulmonary Disease
      (COPD) and asthma. ICS are associated with a decrease in exacerbations and
      improved quality of life in COPD, however multiple studies have linked the
      chronic use of ICSs with an increased risk of developing pneumonia, though the
      effect on mortality is unclear. We review the association of ICS with the risk of
      pneumonia and the implications on clinical outcomes. 

PMID- 25956075
TI  - The formulation of a pressurized metered dose inhaler containing theophylline for
      inhalation.
AB  - BACKGROUND: Theophylline (TP) is a bronchodilator used orally to treat chronic
      obstructive pulmonary disease (COPD) that has been associated with multiple side
      effects, tempering its present use. This study aims to improve COPD treatment by
      creating a low-dose pressurized metered dose inhaler (pMDI) inhalable formulation
      of TP. METHODS: Aerosol performance was assessed using Andersen Cascade Impaction
      (ACI). Solubility of TP in HFA 134/ethanol mixture was measured and morphology of
      the particles analyzed with a scanning electron microscope (SEM). Calu-3 cell
      viability, epithelial cell transport and inflammatory-response assays were
      conducted to study the impact of the formulation on lung epithelial cells.
      RESULTS: The mass deposition profile of the formulation showed an emitted dose of
      250.04+/-14.48MUg per 5 actuations, achieving the designed nominal dose
      (50MUg/dose). SEM showed that the emitted particles were hollow with spherical
      morphology. Approximately 98% of TP was transported across Calu-3 epithelial
      cells and the concentration of interleukin-8 secreted from Calu-3 cells following
      stimulation with tissue necrosis factor-alpha (TNF-alpha) resulted in
      significantly lower level of interleukin-8 released from the cells pre-treated
      with TP (1.92+/-0.77ng.ml(-1) TP treated vs. 8.83+/-2.05ng.ml(-1) TNF-alpha
      stimulated, respectively). CONCLUSIONS: The solution pMDI formulation of TP
      developed in present study was shown to be suitable for inhalation and
      demonstrated anti-inflammatory effects at low doses in Calu-3 cell model.

PMID- 25956076
TI  - Diversity in the organization of centromeric chromatin.
AB  - Centromeric chromatin is distinguished primarily by nucleosomes containing the
      histone variant cenH3, which organizes the kinetochore that links the chromosome
      to the spindle apparatus. Whereas budding yeast have simple 'point' centromeres
      with single cenH3 nucleosomes, and fission yeast have 'regional' centromeres
      without obvious sequence specificity, the centromeres of most organisms are
      embedded in highly repetitive 'satellite' DNA. Recent studies have revealed a
      remarkable diversity in centromere chromatin organization among different
      lineages, including some that have lost cenH3 altogether. We review recent
      progress in understanding point, regional and satellite centromeres, as well as
      less well-studied centromere types, such as holocentromeres. We also discuss the
      formation of neocentromeres, the role of pericentric heterochromatin, and the
      structure and composition of the cenH3 nucleosome. 

PMID- 25956077
TI  - Host shoot clipping depresses the growth of weedy hemiparasitic Pedicularis
      kansuensis.
AB  - Root hemiparasitic plants show optimal growth when attached to a suitable host by
      abstracting water and nutrients. Despite the fact that damage to host plants in
      the wild occurs frequently in various forms (e.g. grazing), effects of host
      damage on growth and physiological performance of root hemiparasites remain
      unclear. In this study, host shoot clipping was conducted to determine the
      influence of host damage on photosynthetic and growth performance of a weedy root
      hemiparasite, Pedicularis kansuensis, and its interaction with a host, Elymus
      nutans. Photosynthetic capacity, tissue mineral nutrient content and plant
      biomass of P. kansuensis were significantly improved when attached to a host
      plant. Host clipping had no effect on quantum efficiency (PhiPSII), but
      significantly reduced the growth rate and biomass of P. kansuensis. In contrast,
      clipping significantly improved photosynthetic capacity and accumulation of
      potassium in E. nutans. No significant decrease in biomass was observed in
      clipped host plants. By changing nutrient absorption and allocation, clipping
      affected the interaction between P. kansuensis and its host. Our results showed
      that host clipping significantly suppressed the growth of weedy P. kansuensis,
      but did not affect biomass accumulation in E. nutans. We propose that grazing (a
      dominant way of causing host damage in the field) may have a potential in the
      control against the weedy hemiparasite. 

PMID- 25956078
TI  - Perspective: Stimulated Raman adiabatic passage: The status after 25 years.
AB  - The first presentation of the STIRAP (stimulated Raman adiabatic passage)
      technique with proper theoretical foundation and convincing experimental data
      appeared 25 years ago, in the May 1st, 1990 issue of The Journal of Chemical
      Physics. By now, the STIRAP concept has been successfully applied in many
      different fields of physics, chemistry, and beyond. In this article, we comment
      briefly on the initial motivation of the work, namely, the study of reaction
      dynamics of vibrationally excited small molecules, and how this initial idea led
      to the documented success. We proceed by providing a brief discussion of the
      physics of STIRAP and how the method was developed over the years, before
      discussing a few examples from the amazingly wide range of applications which
      STIRAP now enjoys, with the aim to stimulate further use of the concept. Finally,
      we mention some promising future directions. 

PMID- 25956079
TI  - Communication: Salt-induced water orientation at a surface of non-ionic
      surfactant in relation to a mechanism of Hofmeister effect.
AB  - The behavior of water molecules at the surface of nonionic surfactant
      (monomyristolein) and effects of monovalent ions on the behavior are investigated
      using the heterodyne-detected vibrational sum frequency generation spectroscopy.
      It is found that water molecules at the surface are oriented with their hydrogen
      atoms pointing to the bulk, and that the degree of orientation depends on the
      anion strongly but weakly on the cation. With measured surface potentials in
      those saline solutions, it is concluded that the heterogeneous distribution of
      anions and cations in combination with the nonionic surfactant causes the water
      orientation. This heterogeneous distribution well explains the contrasting order
      of anions and cations with respect to the ion size in the Hofmeister series. 

PMID- 25956080
TI  - Communication: Does a single CH3CN molecule attached to Ru(bipy)3(2+) affect its
      absorption spectrum?
AB  - Tris(bipyridine)ruthenium(II) (Ru(bipy)3 (2+)) is a prototypical transition metal
      coordination complex whose photophysical properties have attracted considerable
      attention. A much debated issue is whether the metal-to-ligand charge transfer
      (MLCT) transition that accounts for the complex's beautiful red color is fully
      delocalized across all three bipyridine ligands or located on just one ligand.
      Here, we show based on gas-phase action spectroscopy that attachment of a single
      acetonitrile molecule does not change the absorption spectrum from that of the
      bare ions, which is indicative of a delocalized state. However, the gas-phase
      spectra of the bare and one solvent molecule complexes are significantly
      blueshifted relative to that obtained in bulk acetonitrile, which suggests that
      in solution the polarizability of many solvent molecules working together can
      localize the MLCT state. Our data clearly show that more than one solvent
      molecule is needed to break the symmetry of the MLCT excited state and reproduce
      its solution-phase characteristics. 

PMID- 25956081
TI  - Communication: Tolman length and rigidity constants of water and their role in
      nucleation.
AB  - A proper understanding of nucleation is crucial in several natural and industrial
      processes. However, accurate quantitative predictions of this phenomenon have not
      been possible. The most popular tool for calculating nucleation rates, classical
      nucleation theory (CNT), deviates by orders of magnitude from experiments for
      most substances. We investigate whether part of this discrepancy can be accounted
      for by the curvature-dependence of the surface tension. To that end, we evaluate
      the leading order corrections for water, the Tolman length and the rigidity
      constants, using square gradient theory coupled with the accurate cubic plus
      association equation of state. The Helfrich expansion is then used to incorporate
      them into the CNT-framework. For water condensation, the modified framework
      successfully corrects the erroneous temperature dependence of the nucleation
      rates given by the classical theory and reproduces experimental nucleation rates.

PMID- 25956082
TI  - Communication: Nucleation of water on ice nanograins: Size, charge, and quantum
      effects.
AB  - The sticking cross sections of water molecules on cold size-selected water
      clusters have been simulated using classical and quantum (path-integral)
      molecular dynamics trajectories under realistic conditions. The integrated cross
      sections for charged clusters show significant size effects with comparable
      trends as in experiments, as well as essentially no sign effect. Vibrational
      delocalization, although it contributes to enlarging the geometric cross
      sections, leads to a counter-intuitive decrease in the dynamical cross section
      obtained from the trajectories. These results are interpreted based on the
      apparent reduction in the effective interaction between the projectile and the
      target owing to zero-point effects. 

PMID- 25956083
TI  - Communication: Intraparticle segregation of structurally homogeneous
      polyelectrolyte microgels caused by long-range Coulomb repulsion.
AB  - Structurally homogeneous polyelectrolyte microgels in dilute aqueous solutions
      are shown to exhibit inhomogeneous density profile including intraparticle
      "phase" coexistence of hollow core and dense "skin." This effect is a consequence
      of long-range Coulomb repulsion of charged groups which appear because of entropy
      driven escape of monovalent counterions into the outer solvent. Excess of the
      charged groups at the periphery of the microgel particle reduces electrostatic
      energy and overall free energy of the system despite a penalty in the elastic
      free energy of strongly stretched subchains in the hole. This finding can serve
      as additional tool controlling encapsulation, transport, and release of high- and
      low-molecular-weight species in processes where the microgels are used as
      delivery systems. 

PMID- 25956084
TI  - Origin invariance in vibrational resonance Raman optical activity.
AB  - A theoretical investigation on the origin dependence of the vibronic
      polarizabilities, isotropic and anisotropic rotational invariants, and scattering
      cross sections in Resonance Raman Optical Activity (RROA) spectroscopy is
      presented. Expressions showing the origin dependence of these polarizabilities
      were written in the resonance regime using the Franck-Condon (FC) and Herzberg
      Teller (HT) approximations for the electronic transition moments. Differently
      from the far-from-resonance scattering regime, where the origin dependent terms
      cancel out when the rotational invariants are calculated, RROA spectrum can
      exhibit some origin dependence even for eigenfunctions of the electronic
      Hamiltonian. At the FC level, the RROA spectrum is completely origin invariant if
      the polarizabilities are calculated using a single excited state or for a set of
      degenerate states. Otherwise, some origin effects can be observed in the
      spectrum. At the HT level, RROA spectrum is origin dependent even when the
      polarizabilities are evaluated from a single excited state but the origin effect
      is expected to be small in this case. Numerical calculations performed for (S)
      methyloxirane, (2R,3R)-dimethyloxirane, and (R)-4-F-2-azetidinone at both FC and
      HT levels using the velocity representation of the electric dipole and quadrupole
      transition moments confirm the predictions of the theory and show the extent of
      origin effects and the effectiveness of suggested ways to remove them. 

PMID- 25956085
TI  - Semiclassical multi-phonon theory for atom-surface scattering: Application to the
      Cu(111) system.
AB  - The semiclassical perturbation theory of Hubbard and Miller [J. Chem. Phys. 80,
      5827 (1984)] is further developed to include the full multi-phonon transitions in
      atom-surface scattering. A practically applicable expression is developed for the
      angular scattering distribution by utilising a discretized bath of oscillators,
      instead of the continuum limit. At sufficiently low surface temperature good
      agreement is found between the present multi-phonon theory and the previous one-,
      and two-phonon theory derived in the continuum limit in our previous study [Daon,
      Pollak, and Miret-Artes, J. Chem. Phys. 137, 201103 (2012)]. The theory is
      applied to the measured angular distributions of Ne, Ar, and Kr scattered from a
      Cu(111) surface. We find that the present multi-phonon theory substantially
      improves the agreement between experiment and theory, especially at the higher
      surface temperatures. This provides evidence for the importance of multi-phonon
      transitions in determining the angular distribution as the surface temperature is
      increased. 

PMID- 25956086
TI  - A new approach to calculate charge carrier transport mobility in organic
      molecular crystals from imaginary time path integral simulations.
AB  - We present a new non-perturbative method to calculate the charge carrier mobility
      using the imaginary time path integral approach, which is based on the Kubo
      formula for the conductivity, and a saddle point approximation to perform the
      analytic continuation. The new method is first tested using a benchmark
      calculation from the numerical exact hierarchical equations of motion method.
      Imaginary time path integral Monte Carlo simulations are then performed to
      explore the temperature dependence of charge carrier delocalization and mobility
      in organic molecular crystals (OMCs) within the Holstein and Holstein-Peierls
      models. The effects of nonlocal electron-phonon interaction on mobility in
      different charge transport regimes are also investigated. 

PMID- 25956087
TI  - Theory of single molecule emission spectroscopy.
AB  - A general theory and calculation framework for the prediction of frequency
      resolved single molecule photon counting statistics is presented. Expressions for
      the generating function of photon counts are derived, both for the case of naive
      "detection" based solely on photon emission from the molecule and also for
      experimentally realizable detection of emitted photons, and are used to
      explicitly calculate low-order photon-counting moments. The two cases of naive
      detection versus physical detection are compared to one another and it is
      demonstrated that the physical detection scheme resolves certain inconsistencies
      predicted via the naive detection approach. Applications to two different models
      for molecular dynamics are considered: a simple two-level system and a two-level
      absorber subject to spectral diffusion. 

PMID- 25956088
TI  - High-order sampling schemes for path integrals and Gaussian chain simulations of
      polymers.
AB  - In this work, we demonstrate that path-integral schemes, derived in the context
      of many-body quantum systems, benefit the simulation of Gaussian chains
      representing polymers. Specifically, we show how to decrease discretization
      corrections with little extra computation from the usual O(1/P(2)) to O(1/P(4)),
      where P is the number of beads representing the chains. As a consequence, high
      order integrators necessitate much smaller P than those commonly used. Particular
      emphasis is placed on the questions of how to maintain this rate of convergence
      for open polymers and for polymers confined by a hard wall as well as how to
      ensure efficient sampling. The advantages of the high-order sampling schemes are
      illustrated by studying the surface tension of a polymer melt and the interface
      tension in a binary homopolymers blend. 

PMID- 25956089
TI  - Finding mechanochemical pathways and barriers without transition state search.
AB  - In covalent mechanochemistry, precise application of mechanical stress to
      molecules of interest ("mechanophores") is used to induce to promote desired
      reaction pathways. Computational prediction of such phenomena and rational
      mechanophore design involves the computationally costly task of finding relevant
      transition-state saddles on force-deformed molecular potential energy surfaces
      (PESs). Finding a transition state often requires an initial guess about the
      pathway by which the reaction will proceed. Unfortunately, chemical intuition
      often fails when predicting likely consequences of mechanical stress applied to
      molecular systems. Here, we describe a fully deterministic method for finding
      mechanochemically relevant transition states and reaction pathways. The method is
      based on the observation that application of a sufficiently high mechanical force
      will eventually destabilize any molecular structure. Mathematically, such
      destabilization proceeds via a "catastrophe" occurring at a critical force where
      the energy minimum corresponding to the stable molecular structure coalesces with
      a transition state. Catastrophe theory predicts the force-deformed PES to have
      universal behavior in the vicinity of the critical force, allowing us to deduce
      the molecular structure of the transition state just below the critical force
      analytically. We then use the previously developed method of tracking transition
      state evolution with the force to map out the entire reaction path and to predict
      the complete force dependence of the reaction barrier. Beyond its applications in
      mechanochemistry, this approach may be useful as a general method of finding
      transition states using fictitious forces to target specific reaction mechanisms.

PMID- 25956090
TI  - Understanding nuclear motions in molecules: Derivation of Eckart frame ro
      vibrational Hamiltonian operators via a gateway Hamiltonian operator.
AB  - A new ro-vibrational Hamiltonian operator, named gateway Hamiltonian operator,
      with exact kinetic energy term, T^, is presented. It is in the Eckart frame and
      it is of the same form as Watson's normal coordinate Hamiltonian. However, the
      vibrational coordinates employed are not normal coordinates. The new Hamiltonian
      is shown to provide easy access to Eckart frame ro-vibrational Hamiltonians with
      exact T^ given in terms of any desired set of vibrational coordinates. A general
      expression of the Eckart frame ro-vibrational Hamiltonian operator is given and
      some of its properties are discussed. 

PMID- 25956091
TI  - Identification of two-step chemical mechanisms using small temperature
      oscillations and a single tagged species.
AB  - In order to identify two-step chemical mechanisms, we propose a method based on a
      small temperature modulation and on the analysis of the concentration
      oscillations of a single tagged species involved in the first step. The
      thermokinetic parameters of the first reaction step are first determined. Then,
      we build test functions that are constant only if the chemical system actually
      possesses some assumed two-step mechanism. Next, if the test functions plotted
      using experimental data are actually even, the mechanism is attributed and the
      obtained constant values provide the rate constants and enthalpy of reaction of
      the second step. The advantage of the protocol is to use the first step as a
      probe reaction to reveal the dynamics of the second step, which can hence be
      relieved of any tagging. The protocol is anticipated to apply to many mechanisms
      of biological relevance. As far as ligand binding is considered, our approach can
      address receptor conformational changes or dimerization as well as competition
      with or modulation by a second partner. The method can also be used to screen
      libraries of untagged compounds, relying on a tracer whose concentration can be
      spectroscopically monitored. 

PMID- 25956092
TI  - Determining the static electronic and vibrational energy correlations via two
      dimensional electronic-vibrational spectroscopy.
AB  - Changes in the electronic structure of pigments in protein environments and of
      polar molecules in solution inevitably induce a re-adaption of molecular nuclear
      structure. Both changes of electronic and vibrational energies can be probed with
      visible or infrared lasers, such as two-dimensional electronic spectroscopy or
      vibrational spectroscopy. The extent to which the two changes are correlated
      remains elusive. The recent demonstration of two-dimensional electronic
      vibrational (2DEV) spectroscopy potentially enables a direct measurement of this
      correlation experimentally. However, it has hitherto been unclear how to
      characterize the correlation from the spectra. In this paper, we present a
      theoretical formalism to demonstrate the slope of the nodal line between the
      excited state absorption and ground state bleach peaks in the spectra as a
      characterization of the correlation between electronic and vibrational transition
      energies. We also show the dynamics of the nodal line slope is correlated to the
      vibrational spectral dynamics. Additionally, we demonstrate the fundamental 2DEV
      spectral line-shape of a monomer with newly developed response functions. 

PMID- 25956093
TI  - Measuring correlated electronic and vibrational spectral dynamics using line
      shapes in two-dimensional electronic-vibrational spectroscopy.
AB  - Two-dimensional electronic-vibrational (2DEV) spectroscopy is an experimental
      technique that shows great promise in its ability to provide detailed information
      concerning the interactions between the electronic and vibrational degrees of
      freedom in molecular systems. The physical quantities 2DEV is particularly suited
      for measuring have not yet been fully determined, nor how these effects manifest
      in the spectra. In this work, we investigate the use of the center line slope of
      a peak in a 2DEV spectrum as a measure of both the dynamic and static
      correlations between the electronic and vibrational states of a dye molecule in
      solution. We show how this center line slope is directly related to the solvation
      correlation function for the vibrational degrees of freedom. We also demonstrate
      how the strength with which the vibration on the electronic excited state couples
      to its bath can be extracted from a set of 2DEV spectra. These analytical
      techniques are then applied to experimental data from the laser dye 3,3'
      diethylthiatricarbocyanine iodide in deuterated chloroform, where we determine
      the lifetime of the correlation between the electronic transition frequency and
      the transition frequency for the backbone C = C stretch mode to be ~1.7 ps.
      Furthermore, we find that on the electronic excited state, this mode couples to
      the bath ~1.5 times more strongly than on the electronic ground state. 

PMID- 25956094
TI  - Potential energy surface of the CO2-N2 van der Waals complex.
AB  - Four-dimensional potential energy surface (4D-PES) of the atmospherically
      relevant CO2-N2 van der Waals complex is generated using the explicitly
      correlated coupled cluster with single, double, and perturbative triple
      excitation (CCSD(T)-F12) method in conjunction with the augmented correlation
      consistent triple zeta (aug-cc-pVTZ) basis set. This 4D-PES is mapped along the
      intermonomer coordinates. An analytic fit of this 4D-PES is performed. Our
      extensive computations confirm that the most stable form corresponds to a T-shape
      structure where the nitrogen molecule points towards the carbon atom of CO2. In
      addition, we located a second isomer and two transition states in the ground
      state PES of CO2-N2. All of them lay below the CO2 + N2 dissociation limit. This
      4D-PES is flat and strongly anisotropic along the intermonomer coordinates. This
      results in the possibility of the occurrence of large amplitude motions within
      the complex, such as the inversion of N2, as suggested in the recent
      spectroscopic experiments. Finally, we show that the experimentally established
      deviations from the C2v structure at equilibrium for the most stable isomer are
      due to the zero-point out-of-plane vibration correction. 

PMID- 25956095
TI  - BH2 revisited: New, extensive measurements of laser-induced fluorescence
      transitions and ab initio calculations of near-spectroscopic accuracy.
AB  - The spectroscopy of gas phase BH2 has not been explored experimentally since the
      pioneering study of Herzberg and Johns in 1967. In the present work, laser
      induced fluorescence (LIF) spectra of the A(2)B1(Piu)-X (2)A1 band system of
      (11)BH2, (10)BH2, (11)BD2, and (10)BD2 have been observed for the first time. The
      free radicals were "synthesized" by an electric discharge through a precursor
      mixture of 0.5% diborane (B2H6 or B2D6) in high pressure argon at the exit of a
      pulsed valve. A total of 67 LIF bands have been measured and rotationally
      analyzed, 62 of them previously unobserved. These include transitions to a wide
      variety of excited state bending levels, to several stretch-bend combination
      levels, and to three ground state levels which gain intensity through Renner
      Teller coupling to nearby excited state levels. As an aid to vibronic assignment
      of the spectra, very high level hybrid ab initio potential energy surfaces were
      built starting from the coupled cluster singles and doubles with perturbative
      triples (CCSD(T))/aug-cc-pV5Z level of theory for this seven-electron system. In
      an effort to obtain the highest possible accuracy, the potentials were corrected
      for core correlation, extrapolation to the complete basis set limit, electron
      correlation beyond CCSD(T), and diagonal Born-Oppenheimer effects. The spin
      rovibronic states of the various isotopologues of BH2 were calculated for
      energies up to 22 000 cm(-1) above the X (000) level without any empirical
      adjustment of the potentials or fitting to experimental data. The agreement with
      the new LIF data is excellent, approaching near-spectroscopic accuracy (a few cm(
      1)) and has allowed us to understand the complicated spin-rovibronic energy level
      structure even in the region of strong Renner-Teller resonances. 

PMID- 25956096
TI  - Temperature dependence of the cross section for the fragmentation of thymine via
      dissociative electron attachment.
AB  - Providing experimental values for absolute Dissociative Electron Attachment (DEA)
      cross sections for nucleobases at realistic biological conditions is a
      considerable challenge. In this work, we provide the temperature dependence of
      the cross section, sigma, of the dehydrogenated thymine anion (T - H)(-) produced
      via DEA. Within the 393-443 K temperature range, it is observed that sigma varies
      by one order of magnitude. By extrapolating to a temperature of 313 K, the
      relative DEA cross section for the production of the dehydrogenated thymine anion
      at an incident energy of 1 eV decreases by 2 orders of magnitude and the absolute
      value reaches approximately 6 * 10(-19) cm(2). These quantitative measurements
      provide a benchmark for theoretical prediction and also a contribution to a more
      accurate description of the effects of ionizing radiation on molecular medium. 

PMID- 25956097
TI  - Collision-induced Raman scattering by rare-gas atoms: The isotropic spectrum of
      Ne-Ne and its mean polarizability.
AB  - We report the room-temperature isotropic collision-induced light scattering
      spectrum of Ne-Ne over a wide interval of Raman shifts, and we compare it with
      the only available experimental spectrum for that system as well as with spectra
      calculated quantum-mechanically with the employ of advanced ab initio-computed
      data for the incremental mean polarizability. The spectral range previously
      limited to 170 cm(-1) is now extended to 485 cm(-1) allowing us to successfully
      solve the inverse-scattering problem toward an analytic model for the mean
      polarizability that perfectly matches our measurements. We also report the
      depolarization ratio of the scattering process, lingering over the usefulness of
      this property for more stringent checks between the various polarizability
      models. 

PMID- 25956098
TI  - Photodissociation resonances of jet-cooled NO2 at the dissociation threshold by
      CW-CRDS.
AB  - Around 398 nm, the jet-cooled-spectrum of NO2 exhibits a well identified
      dissociation threshold (D0). Combining the continuous-wave absorption-based
      cavity ringdown spectroscopy technique and laser induced fluorescence detection,
      an energy range of ~25 cm(-1) is analyzed at high resolution around D0. In
      addition to the usual molecular transitions to long-lived energy levels, ~115
      wider resonances are observed. The position, amplitude, and width of these
      resonances are determined. The resonance width spreads from ~0.006 cm(-1) (i.e.,
      ~450 ps) to ~0.7 cm(-1) (~4 ps) with large fluctuations. The identification of at
      least two ranges of resonance width versus the excess energy can be associated
      with the opening of the dissociation channels NO2->NO(X(2)Pi1/2, v=0,
      J=1/2+O((3)P2) and NO2->NO(X(2)Pi1/2, v=0, J=3/2)+O((3)P2). This analysis
      corroborates the existence of loose transition states close to the dissociation
      threshold as reported previously and in agreement with the phase space theory
      predictions as shown by Tsuchiya's group [Miyawaki et al., J. Chem. Phys. 99, 254
      264 (1993)]. The data are analyzed in the light of previously reported frequency-
      and time-resolved data to provide a robust determination of averaged unimolecular
      dissociation rate coefficients. The density of reactant levels deduced (rhoreac ~
      11levels/cm(-1)) is discussed versus the density of transitions, the density of
      resonances, and the density of vibronic levels.

PMID- 25956099
TI  - Underlying theory of a model for the Renner-Teller effect in tetra-atomic
      molecules: X(2)Piu electronic state of C2H2(+).
AB  - In the present study, we prove the plausibility of a simple model for the Renner
      Teller effect in tetra-atomic molecules with linear equilibrium geometry by ab
      initio calculations of the electronic energy surfaces and non-adiabatic matrix
      elements for the X(2)Piu state of C2H2 (+). This phenomenon is considered as a
      combination of the usual Renner-Teller effect, appearing in triatomic species,
      and a kind of the Jahn-Teller effect, similar to the original one arising in
      highly symmetric molecules. Only four parameters (plus the spin-orbit constant,
      if the spin effects are taken into account), which can be extracted from ab
      initio calculations carried out at five appropriate (planar) molecular
      geometries, are sufficient for building up the Hamiltonian matrix whose
      diagonalization results in the complete low-energy (bending) vibronic spectrum.
      The main result of the present study is the proof that the diabatization scheme,
      hidden beneath the apparent simplicity of the model, can safely be carried out,
      at small-amplitude bending vibrations, without cumbersome computation of non
      adiabatic matrix elements at large number of molecular geometries. 

PMID- 25956100
TI  - Direct non-Born-Oppenheimer variational calculations of all bound vibrational
      states corresponding to the first rotational excitation of D2 performed with
      explicitly correlated all-particle Gaussian functions.
AB  - Direct variational calculations where the Born-Oppenheimer approximation is not
      assumed are done for all rovibrational states of the D2 molecule corresponding to
      first excited rotational level (the N = 1 states). All-particle explicitly
      correlated Gaussian basis functions are used in the calculations. The exponential
      parameters of the Gaussians are optimized with the aid of analytically calculated
      energy gradient determined with respect to these parameters. The results allow to
      determine the ortho-para spin isomerization energies as a function of the
      vibrational quantum number. 

PMID- 25956102
TI  - Mode specificity in bond selective reactions F + HOD -> HF + OD and DF + OH.
AB  - The influence of vibrational excitations in the partially deuterated water (HOD)
      reactant on its bond selective reactions with F is investigated using a full
      dimensional quantum wave packet method on an accurate global potential energy
      surface. Despite the decidedly early barrier of the F + H2O reaction, reactant
      vibrational excitation in each local stretching mode of HOD is found to
      significantly enhance the reaction which breaks the excited bond. In the mean
      time, excitation of the HOD bending mode also enhances the reaction, but with
      much lower efficacy and weaker bond selectivity. Except for low collision
      energies, all vibrational modes are more effective in promoting the bond
      selective reactions than the translational energy. These results are compared
      with the predictions of the recently proposed sudden vector projection model. 

PMID- 25956101
TI  - Electron attachment to the phthalide molecule.
AB  - Phthalide, the simplest chain of conductive polymer thin film, was investigated
      by means of Electron Transmission Spectroscopy, Negative Ion Mass Spectrometry,
      and density functional theory quantum chemistry. It has been found that formation
      of gas-phase long-lived molecular anions of phthalide around 0.7 eV takes place
      through cleavage of a C-O bond of the pentacyclic ring of the parent molecular
      anion to give a vibrationally excited (electronically more stable) open-ring
      molecular anion. The energy of the transition state for ring opening of the
      parent negative ion is calculated to be 0.65 eV above the neutral ground state of
      the molecule. The energy (2.64 eV) evaluated for the corresponding transition
      state in the neutral molecule is much higher, so that the process of electron
      detachment from the anion must lead to a neutral molecule with its initial
      pentacyclic structure. The average lifetime of the molecular negative ions formed
      at an electron energy of 0.75 eV and 80  degrees C is measured to be about 100
      MUs. The known switching effect of thin phthalide films could stem from the
      presence of a similar open/closed transition state also in the polymer. 

PMID- 25956103
TI  - Infrared spectroscopy of Mg-CO2 and Al-CO2 complexes in helium nanodroplets.
AB  - The catalytic reduction of CO2 to produce hydrocarbon fuels is a topic that has
      gained significant attention. Development of efficient catalysts is a key enabler
      to such approaches, and metal-based catalysts have shown promise towards this
      goal. The development of a fundamental understanding of the interactions between
      CO2 molecules and metal atoms is expected to offer insight into the chemistry
      that occurs at the active site of such catalysts. In the current study, we
      utilize helium droplet methods to assemble complexes composed of a CO2 molecule
      and a Mg or Al atom. High-resolution infrared (IR) spectroscopy and optically
      selected mass spectrometry are used to probe the structure and binding of the
      complexes, and the experimental observations are compared with theoretical
      results determined from ab initio calculations. In both the Mg-CO2 and Al-CO2
      systems, two IR bands are obtained: one assigned to a linear isomer and the other
      assigned to a T-shaped isomer. In the case of the Mg-CO2 complexes, the
      vibrational frequencies and rotational constants associated with the two isomers
      are in good agreement with theoretical values. In the case of the Al-CO2
      complexes, the vibrational frequencies agree with theoretical predictions;
      however, the bands from both structural isomers exhibit significant homogeneous
      broadening sufficient to completely obscure the rotational structure of the
      bands. The broadening is consistent with an upper state lifetime of 2.7 ps for
      the linear isomer and 1.8 ps for the T-shaped isomer. The short lifetime is
      tentatively attributed to a prompt photo-induced chemical reaction between the
      CO2 molecule and the Al atom comprising the complex. 

PMID- 25956104
TI  - Quantum dynamics of (16)O + (36)O2 and (18)O + (32)O2 exchange reactions.
AB  - We present quantum dynamical investigations of (16)O + (36)O2 and (18)O + (32)O2
      exchange reactions using a time-independent quantum mechanical method and an
      accurate global potential energy surface of ozone [Dawes et al., J. Chem. Phys.
      135, 081102 (2011)]. Initial state-selected integral cross sections, rate
      constants, and Boltzmann averaged thermal rate constants are obtained and
      compared with earlier experimental and theoretical results. The computed thermal
      rate constants for the oxygen exchange reactions exhibit a negative temperature
      dependence, as found experimentally. They are in better agreement with the
      experiments than the previous studies on the same reactions. 

PMID- 25956105
TI  - Kinetic isotope effect of the (16)O + (36)O2 and (18)O + (32)O2 isotope exchange
      reactions: Dominant role of reactive resonances revealed by an accurate time
      dependent quantum wavepacket study.
AB  - The O + O2 isotope exchange reactions play an important role in determining the
      oxygen isotopic composition of a number of trace gases in the atmosphere, and
      their temperature dependence and kinetic isotope effects (KIEs) provide important
      constraints on our understanding of the origin and mechanism of these and other
      unusual oxygen KIEs important in the atmosphere. This work reports a quantum
      dynamics study of the title reactions on the newly constructed Dawes-Lolur-Li
      Jiang-Guo (DLLJG) potential energy surface (PES). The thermal reaction rate
      coefficients of both the (18)O + (32)O2 and (16)O + (36)O2 reactions obtained
      using the DLLJG PES exhibit a clear negative temperature dependence, in sharp
      contrast with the positive temperature dependence obtained using the earlier
      modified Siebert-Schinke-Bittererova (mSSB) PES. In addition, the calculated KIE
      shows an improved agreement with the experiment. These results strongly support
      the absence of the "reef" structure in the entrance/exit channels of the DLLJG
      PES, which is present in the mSSB PES. The quantum dynamics results on both PESs
      attribute the marked KIE to strong near-threshold reactive resonances, presumably
      stemming from the mass differences and/or zero point energy difference between
      the diatomic reactant and product. The accurate characterization of the
      reactivity for these near-thermoneutral reactions immediately above the reaction
      threshold is important for correct characterization of the thermal reaction rate
      coefficients. 

PMID- 25956106
TI  - High-resolution (e, 2e + ion) study of electron-impact ionization and
      fragmentation of methane.
AB  - The ionization and fragmentation of methane induced by low-energy (E0 = 66 eV)
      electron-impact is investigated using a reaction microscope. The momentum vectors
      of all three charged final state particles, two outgoing electrons, and one
      fragment ion, are detected in coincidence. Compared to the earlier study [Xu et
      al., J. Chem. Phys. 138, 134307 (2013)], considerable improvements to the
      instrumental mass and energy resolutions have been achieved. The fragment
      products CH4 (+), CH3 (+), CH2 (+), CH(+), and C(+) are clearly resolved. The
      binding energy resolution of DeltaE = 2.0 eV is a factor of three better than in
      the earlier measurements. The fragmentation channels are investigated by
      measuring the ion kinetic energy distributions and the binding energy spectra.
      While being mostly in consistence with existing photoionization studies the
      results show differences including missing fragmentation channels and previously
      unseen channels. 

PMID- 25956107
TI  - Thermodynamic scaling of the shear viscosity of Mie n-6 fluids and their binary
      mixtures.
AB  - In this work, we have evaluated the applicability of the so-called thermodynamic
      scaling and the isomorph frame to describe the shear viscosity of Mie n-6 fluids
      of varying repulsive exponents (n = 8, 12, 18, 24, and 36). Furthermore, the
      effectiveness of the thermodynamic scaling to deal with binary mixtures of Mie n
      6 fluids has been explored as well. To generate the viscosity database of these
      fluids, extensive non-equilibrium molecular dynamics simulations have been
      performed for various thermodynamic conditions. Then, a systematic approach has
      been used to determine the gamma exponent value (gamma) characteristic of the
      thermodynamic scaling approach for each system. In addition, the applicability of
      the isomorph theory with a density dependent gamma has been confirmed in pure
      fluids. In both pure fluids and mixtures, it has been found that the
      thermodynamic scaling with a constant gamma is sufficient to correlate the
      viscosity data on a large range of thermodynamic conditions covering liquid and
      supercritical states as long as the density is not too high. Interestingly, it
      has been obtained that, in pure fluids, the value of gamma is directly
      proportional to the repulsive exponent of the Mie potential. Finally, it has been
      found that the value of gamma in mixtures can be deduced from those of the pure
      component using a simple logarithmic mixing rule. 

PMID- 25956108
TI  - A molecular dynamics study of intramolecular proton transfer reaction of
      malonaldehyde in solution based upon a mixed quantum-classical approximation. II.
      Proton transfer reaction in non-polar solvent.
AB  - The intramolecular proton transfer reaction of malonaldehyde in neon solvent has
      been investigated by mixed quantum-classical molecular dynamics (QCMD)
      calculations and fully classical molecular dynamics (FCMD) calculations.
      Comparing these calculated results with those for malonaldehyde in water reported
      in Part I [A. Yamada, H. Kojima, and S. Okazaki, J. Chem. Phys. 141, 084509
      (2014)], the solvent dependence of the reaction rate, the reaction mechanism
      involved, and the quantum effect therein have been investigated. With FCMD, the
      reaction rate in weakly interacting neon is lower than that in strongly
      interacting water. However, with QCMD, the order of the reaction rates is
      reversed. To investigate the mechanisms in detail, the reactions were categorized
      into three mechanisms: tunneling, thermal activation, and barrier vanishing.
      Then, the quantum and solvent effects were analyzed from the viewpoint of the
      reaction mechanism focusing on the shape of potential energy curve and its
      fluctuations. The higher reaction rate that was found for neon in QCMD compared
      with that found for water solvent arises from the tunneling reactions because of
      the nearly symmetric double-well shape of the potential curve in neon. The
      thermal activation and barrier vanishing reactions were also accelerated by the
      zero-point energy. The number of reactions based on these two mechanisms in water
      was greater than that in neon in both QCMD and FCMD because these reactions are
      dominated by the strength of solute-solvent interactions. 

PMID- 25956109
TI  - Relaxation dynamics in a transient network fluid with competing gel and glass
      phases.
AB  - We use computer simulations to study the relaxation dynamics of a model for oil
      in-water microemulsion droplets linked with telechelic polymers. This system
      exhibits both gel and glass phases and we show that the competition between these
      two arrest mechanisms can result in a complex, three-step decay of the time
      correlation functions, controlled by two different localization lengthscales. For
      certain combinations of the parameters, this competition gives rise to an
      anomalous logarithmic decay of the correlation functions and a subdiffusive
      particle motion, which can be understood as a simple crossover effect between the
      two relaxation processes. We establish a simple criterion for this logarithmic
      decay to be observed. We also find a further logarithmically slow relaxation
      related to the relaxation of floppy clusters of particles in a crowded
      environment, in agreement with recent findings in other models for dense chemical
      gels. Finally, we characterize how the competition of gel and glass arrest
      mechanisms affects the dynamical heterogeneities and show that for certain
      combination of parameters these heterogeneities can be unusually large. By
      measuring the four-point dynamical susceptibility, we probe the cooperativity of
      the motion and find that with increasing coupling this cooperativity shows a
      maximum before it decreases again, indicating the change in the nature of the
      relaxation dynamics. Our results suggest that compressing gels to large densities
      produces novel arrested phases that have a new and complex dynamics. 

PMID- 25956110
TI  - Confinement of two-dimensional rods in slit pores and square cavities.
AB  - Using Monte Carlo simulation, we analyse the behaviour of two-dimensional hard
      rods in four different types of geometric confinement: (i) a slit pore where the
      particles are confined between two parallel walls with homeotropic anchoring;
      (ii) a hybrid slit pore formed by a planar and a homeotropic wall; square
      cavities that frustrate the orientational order by imposing either (iii)
      homeotropic or (iv) planar wall anchoring. We present results for the state
      diagram as a function of the packing fraction and the degree of confinement.
      Under extreme confinement, unexpected states appear with lower symmetries than
      those of the corresponding stable states in bulk, such as the formation of states
      that break the anchoring constraints or the symmetry imposed by the surfaces. In
      both types of square cavities, the particles form disclinations at intermediate
      densities. At high densities, however, the elastic stress is relaxed via the
      formation of domain walls where the director rotates abruptly by 90 degrees . 

PMID- 25956111
TI  - Lattice dynamics and chemical bonding in Sb2Te3 from first-principles
      calculations.
AB  - Pressure effects on the lattice dynamics and the chemical bonding of the three
      dimensional topological insulator, Sb2Te3, have been studied from a first
      principles perspective in its rhombohedral phase. Where it is possible to
      compare, theory agrees with most of the measured phonon dispersions. We find that
      the inclusion of relativistic effects, in terms of the spin-orbit interaction,
      affects the vibrational features to some extend and creates large fluctuations on
      phonon density of state in high frequency zone. By investigations of structure
      and electronic structure, we analyze in detail the semiconductor to metal
      transition at ~2 GPa followed by an electronic topological transition at a
      pressure of ~4.25 GPa. 

PMID- 25956112
TI  - First principles-based multiparadigm, multiscale strategy for simulating complex
      materials processes with applications to amorphous SiC films.
AB  - Progress has recently been made in developing reactive force fields to describe
      chemical reactions in systems too large for quantum mechanical (QM) methods. In
      particular, ReaxFF, a force field with parameters that are obtained solely from
      fitting QM reaction data, has been used to predict structures and properties of
      many materials. Important applications require, however, determination of the
      final structures produced by such complex processes as chemical vapor deposition,
      atomic layer deposition, and formation of ceramic films by pyrolysis of polymers.
      This requires the force field to properly describe the formation of other
      products of the process, in addition to yielding the final structure of the
      material. We describe a strategy for accomplishing this and present an example of
      its use for forming amorphous SiC films that have a wide variety of applications.
      Extensive reactive molecular dynamics (MD) simulations have been carried out to
      simulate the pyrolysis of hydridopolycarbosilane. The reaction products all agree
      with the experimental data. After removing the reaction products, the system is
      cooled down to room temperature at which it produces amorphous SiC film, for
      which the computed radial distribution function, x-ray diffraction pattern, and
      the equation of state describing the three main SiC polytypes agree with the data
      and with the QM calculations. Extensive MD simulations have also been carried out
      to compute other structural properties, as well the effective diffusivities of
      light gases in the amorphous SiC film. 

PMID- 25956113
TI  - Influence of ion pairing in ionic liquids on electrical double layer structures
      and surface force using classical density functional approach.
AB  - We explore the influence of ion pairing in room temperature ionic liquids
      confined by planar electrode surfaces. Using a coarse-grained model for the
      aromatic ionic liquid [C4MIM(+)][BF4 (-)], we account for an ion pairing
      component as an equilibrium associating species within a classical density
      functional theory. We investigated the resulting structure of the electrical
      double layer as well as the ensuing surface forces and differential capacitance,
      as a function of the degree of ion association. We found that the short-range
      structure adjacent to surfaces was remarkably unaffected by the degree of ion
      pairing, up to several molecular diameters. This was even the case for 100% of
      ions being paired. The physical implications of ion pairing only become apparent
      in equilibrium properties that depend upon the long-range screening of charges,
      such as the asymptotic behaviour of surface forces and the differential
      capacitance, especially at low surface potential. The effect of ion pairing on
      capacitance is consistent with their invocation as a source of the anomalous
      temperature dependence of the latter. This work shows that ion pairing effects on
      equilibrium properties are subtle and may be difficult to extract directly from
      simulations. 

PMID- 25956114
TI  - A new equation of state of a flexible-chain polyelectrolyte solution: Phase
      equilibria and osmotic pressure in the salt-free case.
AB  - We develop a first-principle equation of state of salt-free polyelectrolyte
      solution in the limit of infinitely long flexible polymer chains in the framework
      of a field-theoretical formalism beyond the linear Debye-Hueckel theory and
      predict a liquid-liquid phase separation induced by a strong correlation
      attraction. As a reference system, we choose a set of two subsystems-charged
      macromolecules immersed in a structureless oppositely charged background created
      by counterions (polymer one component plasma) and counterions immersed in
      oppositely charged background created by polymer chains (hard-core one component
      plasma). We calculate the excess free energy of polymer one component plasma in
      the framework of modified random phase approximation, whereas a contribution of
      charge densities' fluctuations of neutralizing backgrounds we evaluate at the
      level of Gaussian approximation. We show that our theory is in a very good
      agreement with the results of Monte Carlo and MD simulations for critical
      parameters of liquid-liquid phase separation and osmotic pressure in a wide range
      of monomer concentration above the critical point, respectively. 

PMID- 25956115
TI  - Heat capacity anomaly in a self-aggregating system: Triblock copolymer 17R4 in
      water.
AB  - The reverse Pluronic, triblock copolymer 17R4 is formed from poly(propylene
      oxide) (PPO) and poly(ethylene oxide) (PEO): PPO14 - PEO24 - PPO14, where the
      number of monomers in each block is denoted by the subscripts. In water, 17R4 has
      a micellization line marking the transition from a unimer network to self
      aggregated spherical micelles which is quite near a cloud point curve above which
      the system separates into copolymer-rich and copolymer-poor liquid phases. The
      phase separation has an Ising-like, lower consolute critical point with a well
      determined critical temperature and composition. We have measured the heat
      capacity as a function of temperature using an adiabatic calorimeter for three
      compositions: (1) the critical composition where the anomaly at the critical
      point is analyzed, (2) a composition much less than the critical composition with
      a much smaller spike when the cloud point curve is crossed, and (3) a composition
      near where the micellization line intersects the cloud point curve that only
      shows micellization. For the critical composition, the heat capacity anomaly very
      near the critical point is observed for the first time in a Pluronic/water system
      and is described well as a second-order phase transition resulting from the
      copolymer-water interaction. For all compositions, the onset of micellization is
      clear, but the formation of micelles occurs over a broad range of temperatures
      and never becomes complete because micelles form differently in each phase above
      the cloud point curve. The integrated heat capacity gives an enthalpy that is
      smaller than the standard state enthalpy of micellization given by a van't Hoff
      plot, a typical result for Pluronic systems. 

PMID- 25956116
TI  - Polymer translocation into and out of an ellipsoidal cavity.
AB  - Monte Carlo simulations are used to study the translocation of a polymer into and
      out of an ellipsoidal cavity through a narrow pore. We measure the polymer free
      energy F as a function of a translocation coordinate, s, defined to be the number
      of bonds that have entered the cavity. To study polymer insertion, we consider
      the case of a driving force acting on monomers inside the pore, as well as
      monomer attraction to the cavity wall. We examine the changes to F(s) upon
      variation in the shape anisometry and volume of the cavity, the polymer length,
      and the strength of the interactions driving the insertion. For athermal systems,
      the free energy functions are analyzed using a scaling approach, where we treat
      the confined portion of the polymer to be in the semi-dilute regime. The free
      energy functions are used with the Fokker-Planck (FP) equation to calculate mean
      translocation times, as well as translocation time distributions. We find that
      both polymer ejection and insertion are faster for ellipsoidal cavities than for
      spherical cavities. The results are in qualitative agreement with those of a
      Langevin dynamics study in the case of ejection but not for insertion. The
      discrepancy is likely due to out-of-equilibrium conformational behaviour that is
      not accounted for in the FP approach. 

PMID- 25956117
TI  - Entropic attraction: Polymer compaction and expansion induced by nano-particles
      in confinement.
AB  - We investigated nanoparticle (NP)-induced coil-to-globule transition of a semi
      flexible polymer in a confined suspension of ideal NP using Langevin dynamics.
      DNA molecules are often found to be highly compact, bound with oppositely charged
      proteins in a crowded environment within cells and viruses. Recent studies found
      that high concentration of electrostatically neutral NP also condenses DNA due to
      entropically induced depletion attraction between DNA segments. Langevin dynamics
      simulations with a semi-flexible chain under strong confinement were performed to
      investigate the competition between NP-induced monomer-monomer and monomer-wall
      attraction under different confinement heights and NP volume fractions. We found
      that whether NP induce polymer segments to adsorb to the walls and swell or to
      attract one another and compact strongly depends on the relative strength of the
      monomer-wall and the NP-wall interactions. 

PMID- 25956118
TI  - Extended law of corresponding states for protein solutions.
AB  - The so-called extended law of corresponding states, as proposed by Noro and
      Frenkel [J. Chem. Phys. 113, 2941 (2000)], involves a mapping of the phase
      behaviors of systems with short-range attractive interactions. While it has
      already extensively been applied to various model potentials, here we test its
      applicability to protein solutions with their complex interactions. We
      successfully map their experimentally determined metastable gas-liquid binodals,
      as available in the literature, to the binodals of short-range square-well
      fluids, as determined by previous as well as new Monte Carlo simulations. This is
      achieved by representing the binodals as a function of the temperature scaled
      with the critical temperature (or as a function of the reduced second virial
      coefficient) and the concentration scaled by the cube of an effective particle
      diameter, where the scalings take into account the attractive and repulsive
      contributions to the interaction potential, respectively. The scaled binodals of
      the protein solutions coincide with simulation data of the adhesive hard-sphere
      fluid. Furthermore, once the repulsive contributions are taken into account by
      the effective particle diameter, the temperature dependence of the reduced second
      virial coefficients follows a master curve that corresponds to a linear
      temperature dependence of the depth of the square-well potential. We moreover
      demonstrate that, based on this approach and cloud-point measurements only,
      second virial coefficients can be estimated, which we show to agree with values
      determined by light scattering or by Derjaguin-Landau-Verwey-Overbeek (DLVO)
      based calculations. 

PMID- 25956119
TI  - Effect of excluded volume on the rheology and transport dynamics of randomly
      hyperbranched polymers.
AB  - The rheology and transport dynamics of the randomly hyperbranched polymers with
      excluded volume interactions are investigated within the tenets of the Rouse-Zimm
      theory. The excluded volume interactions typically account for an effective co
      volume between the nearest non-bonded monomers, modeled through a delta function
      pseudopotential, while the strength of such interactions is evaluated from the
      possible geometric orientations of the bonds. The mechanical moduli are primarily
      determined by the smaller eigenvalues corresponding to the collective modes.
      These modes with smaller relaxation rates increase with the decrease in the
      strength of excluded volume interaction parameter, while the local modes with
      higher relaxation rates remain unaffected. The internal structure of the randomly
      hyperbranched polymer is reflected in the intermediate frequency regime of the
      mechanical relaxation moduli, where the characteristic power-law behavior implies
      the fractal nature of the randomly hyperbranched polymers. The length of this
      power-law region increases either with the decrease in the strength of excluded
      volume interactions or with the increase in the number of shells of the randomly
      hyperbranched polymer, while the numerical values of the power-law exponents are
      strongly affected by the strength of excluded volume interactions. Intrinsic
      viscosity increases linearly for lower values of the excluded volume interaction
      parameters, while depicting a non-linear trend at higher strengths of excluded
      volume interactions. The randomly hyperbranched polymers are relatively more
      compact compared to the star polymer but less compact than that of dendrimers
      with the same number of monomers and same strength of excluded volume
      interactions. The values of the scaling exponents of the diffusion coefficient
      increase with decreasing the strength of excluded volume interactions. The
      scaling exponents of the diffusion coefficient of randomly hyperbranched polymers
      calculated with excluded volume exactly match with the earlier experimental
      results for hyperbranched polyglycidols in poly(vinyl alcohol) solutions. 

PMID- 25956120
TI  - Volume phase transitions of cholesteric liquid crystalline gels.
AB  - We present a mean field theory to describe anisotropic deformations of a
      cholesteric elastomer without solvent molecules and a cholesteric liquid
      crystalline gel immersed in isotropic solvents at a thermal equilibrium state.
      Based on the neoclassical rubber theory of nematic elastomers, we derive an
      elastic energy and a twist distortion energy, which are important to determine
      the shape of a cholesteric elastomer (or gel). We demonstrate that when the
      elastic energy dominates in the free energy, the cholesteric elastomer causes a
      spontaneous compression in the pitch axis and elongates along the director on the
      plane perpendicular to the pitch axis. Our theory can qualitatively describe the
      experimental results of a cholesteric elastomer. We also predict the first-order
      volume phase transitions and anisotropic deformations of a gel at the cholesteric
      isotropic phase transition temperature. Depending on a chirality of a gel, we
      find a prolate or oblate shape of cholesteric gels. 

PMID- 25956121
TI  - Probing the cross-effect of strains in non-linear elasticity of nearly regular
      polymer networks by pure shear deformation.
AB  - The pure shear deformation of the Tetra-polyethylene glycol gels reveals the
      presence of an explicit cross-effect of strains in the strain energy density
      function even for the polymer networks with nearly regular structure including no
      appreciable amount of structural defect such as trapped entanglement. This result
      is in contrast to the expectation of the classical Gaussian network model (Neo
      Hookean model), i.e., the vanishing of the cross effect in regular networks with
      no trapped entanglement. The results show that (1) the cross effect of strains is
      not dependent on the network-strand length; (2) the cross effect is not affected
      by the presence of non-network strands; (3) the cross effect is proportional to
      the network polymer concentration including both elastically effective and
      ineffective strands; (4) no cross effect is expected exclusively in zero limit of
      network concentration in real polymer networks. These features indicate that the
      real polymer networks with regular network structures have an explicit cross
      effect of strains, which originates from some interaction between network strands
      (other than entanglement effect) such as nematic interaction, topological
      interaction, and excluded volume interaction. 

PMID- 25956122
TI  - Binding kinetics of lock and key colloids.
AB  - Using confocal microscopy and first passage time analysis, we measure and predict
      the rates of formation and breakage of polymer-depletion-induced bonds between
      lock-and-key colloidal particles and find that an indirect route to bond
      formation is accessed at a rate comparable to that of the direct formation of
      these bonds. In the indirect route, the pocket of the lock particle is accessed
      by nonspecific bonding of the key particle with the lock surface, followed by
      surface diffusion leading to specific binding in the pocket of the lock. The
      surprisingly high rate of indirect binding is facilitated by its high entropy
      relative to that of the pocket. Rate constants for forward and reverse
      transitions among free, nonspecific, and specific bonds are reported, compared to
      theoretical values, and used to determine the free energy difference between the
      nonspecific and specific binding states. 

PMID- 25956123
TI  - On the rupture of DNA molecule.
AB  - Using Langevin dynamics simulations, we study effects of the shear force on the
      rupture of a double stranded DNA molecule. The model studied here contains two
      single diblock copolymers interacting with each other. The elastic constants of
      individual segments of diblock copolymer are considered to be different. We
      showed that the magnitude of the rupture force depends on whether the force is
      applied at 3' - 3' - ends or 5' - 5' - ends. Distributions of extension in
      hydrogen bonds and covalent bonds along the chain show the striking differences.
      Motivated by recent experiments, we have also calculated the variation of rupture
      force for different chain lengths. Results obtained from simulations have been
      validated with the analytical calculation based on the ladder model of DNA. 

PMID- 25956124
TI  - A molecular dynamics investigation of the planar elongational rheology of
      chemically identical dendrimer-linear polymer blends.
AB  - The structure and rheology of model polymer blends under planar elongational flow
      have been investigated through nonequilibrium molecular dynamics simulations. The
      polymeric blends consist of linear polymer chains (187 monomers per chain) and
      dendrimer polymers of generations g = 1 - 4. The number fraction, x, of the
      dendrimer species is varied (4%, 8%, and 12%) in the blend melt. We study the
      effect of extension rate, dendrimer generation, and dendrimer number fraction on
      pair distribution functions for different blend systems. We also calculate the
      extension-rate dependent radius of gyration and ratios of the eigenvalues of the
      gyration tensor to study the elongation-induced deformation of the molecules in
      the blend. Melt rheological properties including the first and second extensional
      viscosities are found to fall into the range between those of pure dendrimer and
      pure linear polymer melts, which are correlated with the mass fraction and
      generation of the dendrimers in the blend. 

PMID- 25956125
TI  - An accurate and efficient computation method of the hydration free energy of a
      large, complex molecule.
AB  - The hydration free energy (HFE) is a crucially important physical quantity to
      discuss various chemical processes in aqueous solutions. Although an explicit
      solvent computation with molecular dynamics (MD) simulations is a preferable
      treatment of the HFE, huge computational load has been inevitable for large,
      complex solutes like proteins. In the present paper, we propose an efficient
      computation method for the HFE. In our method, the HFE is computed as a sum of
      <UUV>/2 (<UUV> is the ensemble average of the sum of pair interaction energy
      between solute and water molecule) and the water reorganization term mainly
      reflecting the excluded volume effect. Since <UUV> can readily be computed
      through a MD of the system composed of solute and water, an efficient computation
      of the latter term leads to a reduction of computational load. We demonstrate
      that the water reorganization term can quantitatively be calculated using the
      morphometric approach (MA) which expresses the term as the linear combinations of
      the four geometric measures of a solute and the corresponding coefficients
      determined with the energy representation (ER) method. Since the MA enables us to
      finish the computation of the solvent reorganization term in less than 0.1 s once
      the coefficients are determined, the use of the MA enables us to provide an
      efficient computation of the HFE even for large, complex solutes. Through the
      applications, we find that our method has almost the same quantitative
      performance as the ER method with substantial reduction of the computational
      load. 

PMID- 25956126
TI  - Nitrogen K-edge x-ray absorption near edge structure of pyrimidine-containing
      nucleotides in aqueous solution.
AB  - X-ray absorption near edge structure (XANES) was measured at energies around the
      N K-edge of the pyrimidine-containing nucleotides, cytidine 5'-monophosphate
      (CMP), 2'-deoxythymidine 5'-monophosphate (dTMP), and uridine 5'-monophosphate
      (UMP), in aqueous solutions and in dried films under various pH conditions. The
      features of resonant excitations below the N K-edge in the XANES spectra for CMP,
      dTMP, and UMP changed depending on the pH of the solutions. The spectral change
      thus observed is systematically explained by the chemical shift of the core
      levels of N atoms in the nucleobase moieties caused by structural changes due to
      protonation or deprotonation at different proton concentrations. This
      interpretation is supported by the results of theoretical calculations using
      density functional theory for the corresponding nucleobases in the neutral and
      protonated or deprotonated forms. 

PMID- 25956128
TI  - Bias-dependent effects in planar perovskite solar cells based on CH3NH3PbI(3
      x)Clx films.
AB  - A unique bias-dependent phenomenon in CH3NH3PbI(3-x)Cl(x) based planar perovskite
      solar cells has been demonstrated, in which the photovoltaic parameters derived
      from the current-voltage (I-V) curves are highly dependent on the initial
      positive bias of the I-V measurement. In FTO/CH3NH3PbI(3-x)Cl(x)/Au devices, the
      open-circuit voltage and short-circuit current increased by ca. 337.5% and 281.9%
      respectively, by simply increasing the initial bias from 0.5 V to 2.5 V.

PMID- 25956127
TI  - Improving the Social Skills of Children with HFASD: An Intervention Study.
AB  - The present study examines the efficacy of a social skills and Theory of Mind
      (S.S.ToM) intervention for children with high-functioning ASD. Children were
      taught to identify and consider their peer's mental states, e.g., knowledge,
      emotions, desires, beliefs, intentions, likes and dislikes, while learning
      friendship-making skills and strategies, through the use of visual scaffolds in
      story format. Compared to two control groups, S.S.ToM participants demonstrated
      significantly greater gains on measures of Theory of Mind and social
      responsiveness. At a 3-month follow-up assessment, improvements appeared to have
      been maintained and continued gains were observed. These results provide support
      for the utility of a visually supported Theory of Mind and social skills
      intervention that may be delivered in community settings. 

PMID- 25956129
TI  - Drug delivery with nanospherical supramolecular cell penetrating peptide-taxol
      conjugates containing a high drug loading.
AB  - HYPOTHESIS: Supramolecular nanostructures via small molecule self-assembly hold
      great promise for controlled delivery of hydrophobic anticancer drugs.
      Particularly, taxol has recently been discovered to possess excellent self
      assembly property, which may provide new opportunities to develop a new class of
      functional supramolecular nanomaterials for drug delivery application.
      EXPERIMENTS: A cell penetrating peptide (CPP)-taxol conjugate (Taxol-CPP) was
      designed and synthesized. The self-assembling property of Taxol-CPP was
      investigated and the resultant nanomaterials were well characterized.
      Subsequently, the cytotoxicity of the Taxol-CPP after self-assembly against HepG2
      cancer cells was evaluated. FINDINGS: It is found that the Taxol-CPP possesses a
      high drug loading of 26.4% in each molecule, which is able to self-assemble into
      supramolecular nanospheres. By taking advantages of the self-assembly ability of
      taxol, Taxol-CPP supramolecular nanospheres with a mean size of around 130 nm can
      be obtained, composed of only the functional peptide (CPP) and the drug (taxol).
      Furthermore, we have demonstrated that the Taxol-CPP nanospheres do not
      compromise the taxol's potency, which can also be utilized as the carriers for co
      delivery of another anticancer drug (doxorubicin).

PMID- 25956130
TI  - Expression of SATB1 and HER2 in breast cancer and the correlations with
      clinicopathologic characteristics.
AB  - BACKGROUND: Special AT-rich sequence binding protein 1 (SATB1) is found acting as
      a "genome organizer" that functions as a landing platform to regulate tissue
      specific gene ex-pression. In breast cancer cell lines it has been proven that
      SATB1 could upregulate the expression of the HER2. In this paper, the relevance
      of SATB1 and HER2 expression was assessed in human breast cancer tissues, and
      their influence on tumor histological grade and patients' survival was explored.
      METHODS: Using immunohistochemistry (IHC) and fluorescence in situ hybridization
      (FISH), 169 patients with breast cancer were assessed for SATB1 expression, HER2
      amplification and hormone-receptor (HR) expression. The effects of SATB1
      expression on HER2 and HR expression as well as their association with
      clinicopathologic characteristics were further analyzed by statistical
      evaluation. RESULTS: SATB1 expression was correlated with HER2 expression in
      breast cancer(r = 0.191; p = 0.013). SATB1, HER2 and SATB1/HER2 co-expression was
      negatively correlated with HR expression (r = -0.228, p = 0.003; r = -0.338, p =
      0.000; r = -0.527, p = 0.000, respectively). SATB1 and HER2 single positive and
      their co-expression were all significantly correlated with higher histological
      grade (r = 0.239, p = 0.002; r = 0.160, p = 0.038; r = 0.306, p = 0.003,
      respectively). Multivariate cox regression analyses showed that SATB1 and HER2
      were independent risk factors for breast cancer patients, while HR was a
      protective factor for patients' survival. Comparing to SATB1 or HER2 single
      positive expression, SATB1/HER2 co-expression tended to have even worse
      prognosis. CONCLUSIONS: SATB1 and HER2 performed a synergistic effect in breast
      cancer. Their expression correlated with poorly differentiated breast cancer and
      indicated an unfavorable prognosis. VIRTUAL SLIDES: The virtual slide(s) for this
      article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1400555050159723 .

PMID- 25956131
TI  - Acetyl salicylic acid protected against heat stress damage in chicken myocardial
      cells and may associate with induced Hsp27 expression.
AB  - We investigated whether acetyl salicylic acid (ASA) protects chicken myocardial
      cells from heat stress-mediated damage in vivo and whether the induction of Hsp27
      expression is connected with this function. Pathological changes, damage-related
      enzyme levels, and Hsp27 expression were studied in chickens following heat
      stress (40 +/- 1  degrees C for 0, 1, 2, 3, 5, 7, 10, 15, or 24 h, respectively)
      with or without ASA administration (1 mg/kg BW, 2 h prior). Appearance of
      pathological lesions such as degenerations and karyopyknosis as well as the
      myocardial damage-related enzyme activation indicated that heat stress causes
      considerable injury to the myocardial cells in vivo. Myocardial cell injury was
      most serious in chickens exposed to heat stress without prior ASA administration;
      meanwhile, ASA pretreatment acted protective function against high temperature
      induced injury. Hsp27 expression was induced under all experimental conditions
      but was one-fold higher in the ASA-pretreated animals (0.3138 +/- 0.0340 ng/mL)
      than in untreated animals (0.1437 +/- 0.0476 ng/mL) 1 h after heat stress
      exposure, and such an increase was sustained over the length of the experiment.
      Our findings indicate that pretreatment with ASA protects chicken myocardial
      cells from acute heat stress in vivo with almost no obvious side effects, and
      this protection may involve an enhancement of Hsp27 expression. However, the
      detailed mechanisms underlying this effect require further investigation.

PMID- 25956132
TI  - Identification of pneumococcal colonization determinants in the stringent
      response pathway facilitated by genomic diversity.
AB  - BACKGROUND: Understanding genetic determinants of a microbial phenotype generally
      involves creating and comparing isogenic strains differing at the locus of
      interest, but the naturally existing genomic and phenotypic diversity of
      microbial populations has rarely been exploited. Here we report use of a diverse
      collection of 616 carriage isolates of Streptococcus pneumoniae and their genome
      sequences to help identify a novel determinant of pneumococcal colonization.
      RESULTS: A spontaneously arising laboratory variant (SpnYL101) of a capsule
      switched TIGR4 strain (TIGR4:19F) showed reduced ability to establish mouse nasal
      colonization and lower resistance to non-opsonic neutrophil-mediated killing in
      vitro, a phenotype correlated with in vivo success. Whole genome sequencing
      revealed 5 single nucleotide polymorphisms (SNPs) affecting 4 genes in SpnYL101
      relative to its ancestor. To evaluate the effect of variation in each gene, we
      performed an in silico screen of 616 previously published genome sequences to
      identify pairs of closely-related, serotype-matched isolates that differ at the
      gene of interest, and compared their resistance to neutrophil-killing. This
      method allowed rapid examination of multiple candidate genes and found phenotypic
      differences apparently associated with variation in SP_1645, a RelA/ SpoT homolog
      (RSH) involved in the stringent response. To establish causality, the alleles
      corresponding to SP_1645 were switched between the TIGR4:19F and SpnYL101. The
      wild-type SP_1645 conferred higher resistance to neutrophil-killing and
      competitiveness in mouse colonization. Using a similar strategy, variation in
      another RSH gene (TIGR4 locus tag SP_1097) was found to alter resistance to
      neutrophil-killing. CONCLUSIONS: These results indicate that analysis of
      naturally existing genomic diversity complements traditional genetics approaches
      to accelerate genotype-phenotype analysis.

PMID- 25956134
TI  - Diagnostic performance characteristics of a rapid field test for anthrax in
      cattle.
AB  - Although diagnosis of anthrax can be made in the field with a peripheral blood
      smear, and in the laboratory with bacterial culture or molecular based tests,
      these tests require either considerable experience or specialised equipment. Here
      we report on the evaluation of the diagnostic sensitivity and specificity of a
      simple and rapid in-field diagnostic test for anthrax, the anthrax
      immunochromatographic test (AICT). The AICT detects the protective antigen (PA)
      component of the anthrax toxin present within the blood of an animal that has
      died from anthrax. The test provides a result in 15min and offers the advantage
      of avoiding the necessity for on-site necropsy and subsequent occupational risks
      and environmental contamination. The specificity of the test was determined by
      testing samples taken from 622 animals, not infected with Bacillus anthracis.
      Diagnostic sensitivity was estimated on samples taken from 58 animals, naturally
      infected with B. anthracis collected over a 10-year period. All samples used to
      estimate the diagnostic sensitivity and specificity of the AICT were also tested
      using the gold standard of bacterial culture. The diagnostic specificity of the
      test was estimated to be 100% (99.4-100%; 95% CI) and the diagnostic sensitivity
      was estimated to be 93.1% (83.3-98.1%; 95% CI) (Clopper-Pearson method). Four
      samples produced false negative AICT results. These were among 9 samples, all of
      which tested positive for B. anthracis by culture, where there was a time delay
      between collection and testing of >48h and/or the samples were collected from
      animals that were >48h post-mortem. A statistically significant difference
      (P<0.001; Fishers exact test) was found between the ability of the AICT to detect
      PA in samples from culture positive animals <48h post-mortem, 49 of 49, Se=100%
      (92.8-100%; 95% CI) compared with samples tested >48h post-mortem 5 of 9 Se=56%
      (21-86.3%; 95% CI) (Clopper-Pearson method). Based upon these results a post hoc
      cut-off for use of the AICT of 48h post-mortem was applied, Se=100% (92.8-100%;
      95% CI) and Sp=100% (99.4-100%; 95% CI). The high diagnostic sensitivity and
      specificity and the simplicity of the AICT enables it to be used for active
      surveillance in areas with a history of anthrax, or used as a preliminary tool in
      investigating sudden, unexplained death in cattle. 

PMID- 25956133
TI  - Biological parameters predictive of percent dense red blood cell decrease under
      hydroxyurea.
AB  - BACKGROUND: Dense red blood cells (DRBCs) are associated with chronic clinical
      manifestations of sickle-cell-disease (SCD). Hydroxyurea (HU) decreases the
      percent (%) DRBCs, thereby improving its therapeutic benefits, especially the
      prevention of SCD clinical complications, but parameters influencing %DRBCs
      remain unknown. The purpose of this study was to determine predictive biological
      parameters of %DRBC decline under HU. METHODS: Factors affecting the %DRBC
      decrease in SCD patients HU-treated for >=6 months were analyzed. Biological
      parameters and the %DRBCs were determined before starting HU and after >=6 months
      of HU intake. Bivariate analyses evaluated the impact of each biological
      parameter variation on %DRBC changes under treatment. Multivariate analyses
      assessed the correlations between the decreased %DRBCs and biological parameters.
      RESULTS: The %DRBCs declined by 40.95% after >=6 months on HU. That decrease was
      associated with less hemolysis, however in several analyses on this group of
      patients we did not find a statistically significant correlation between decrease
      in %DRBCs and increase in HbF. Initial %DRBC values were the most relevant
      parameter to predict %DRBC decline. CONCLUSION: Our results strengthen the known
      HU efficacy in SCD management statistically independently of the classical HbF
      biological response. Decreasing %DRBCs is essential to limiting chronic SCD
      symptoms related to DRBCs and predictive factors might help prevent those
      manifestations. The results of this study provide new perspectives on indication
      for HU use, i.e., to prevent SCD-induced organ damage.

PMID- 25956136
TI  - Erratum to: objective volumetric comparison of room air versus carbon dioxide for
      colonic distention at screening CT colonography.

PMID- 25956135
TI  - Emergency visits among end-of-life cancer patients in Taiwan: a nationwide
      population-based study.
AB  - BACKGROUND: An increased number of emergency visits at the end of life may
      indicate poor-quality cancer care. The study aimed to investigate the prevalence
      and utilization of emergency visits and to explore the reasons for emergency
      department (ED) visits among cancer patients at the end of life. METHODS: A
      retrospective cohort study was performed by tracking one year of ambulatory
      medical service records before death. Data were collected from the cancer dataset
      of Taiwan's National Health Insurance Research Database (NHIRD). RESULTS: A total
      of 32,772 (19.2%) patients with malignant cancer visited EDs, and 23,883 patients
      died during the study period. Of these, the prevalence of emergency visits in the
      mortality group was 81.5%, and their ED utilization was significantly increased
      monthly to the end of life. The most frequent types of cancer were digestive and
      peritoneum cancers (34.8%), followed by breast cancer (17.7%) and head and neck
      cancers (13.3%). Older patients, males, and those diagnosed with metastases,
      respiratory or digestive cancer were more likely to use ED services at the end of
      life. Use of an ED service in the nearest community hospital to replace medical
      centers for dying cancer patients would be more acceptable in emergency
      situations. CONCLUSIONS: Our study provided population-based evidence related to
      ED utilization. An understanding of the reasons for such visits could be useful
      in preventing overuse of ED visits to improve the quality of end-of-life care.

PMID- 25956137
TI  - An X0 shim coil for precise magic-angle adjustment.
AB  - A new method for precise setting of the spinning angle to the magic angle by
      using a saddle coil is described. The coil, which is referred to as an X0 shim
      coil, is wound to produce a uniform static magnetic field Bx perpendicular to the
      main magnetic field B0. The magnetic field felt by a sample is a vector sum of
      the main field B0 and the transverse field Bx produced by the X0 shim coil. Hence
      the angle between the spinner axis and the effective magnetic field can be
      controlled by current I supplied to the X0 shim coil, leading to precise angle
      adjustment without backlash accompanied with a mechanical system conventionally
      used. It is shown that the angle range achieved is +/-0.05 degrees  for I=+/-5A
      at B0=7T. 

PMID- 25956138
TI  - Low-dose lung CT processing using weighted intensity averaging over large-scale
      neighborhoods.
AB  - The aim of the proposed work is to improve low-dose lung CT (LDCT) screening
      using the processing of weighted intensity averaging over large-scale
      neighborhoods (WIA-LN). Both current and voltage reductions were considered for
      LDCT imaging. In the WIA-LN method, the processed pixel intensities are
      calculated by weighted averaging intensities among a large neighboring region.
      The weights are determined by the inter-similarity of the surrounding textures. A
      compute unified device architecture based parallelization was applied to
      accelerate the implementation. To evaluate the effectiveness of the proposed
      processing, low-dose lung CT images were obtained under both 75 % reduced tube
      current and 33.3 % reduced tube voltage condition respectively from a 16 detector
      rows Siemens CT. The standard routine standard-dose CT images were also collected
      as the reference images. In addition to clinical data from patients, an
      anthropomorphic lung phantom was also used in the study. Visual comparison and
      statistical qualitative analysis of image quality scores on the datasets are made
      in validation. Compared to the original LDCT images, improved visual and
      qualitative performance can be observed for the processed images. Statistically
      significant improvement of noise/artifacts suppression and nodule structure
      enhancement are achieved by using the proposed method (P < 0.05). The proposed
      method is capable of providing LDCT images under significantly reduced tube
      current and voltage settings in low-dose condition. Quality of the processed
      images was assessed by radiology specialists. Parallelization based algorithm
      optimization was also performed to increase the clinical applicability of the
      proposed processing. 

PMID- 25956140
TI  - Relations among EEG-alpha asymmetry and positivity personality trait.
AB  - The present study investigates cortical structures associated with personality
      dimension of positivity (POS) by using a standardized low-resolution brain
      electromagnetic tomography (sLORETA), which provides EEG localization measures
      that are independent of the recording reference. Resting EEG and self-report
      measures of positivity, self-esteem, life satisfaction, and optimism were
      collected from 51 female undergraduates. EEG was recorded across 29 scalp sites.
      Anterior and posterior source alpha asymmetries of cortical activation were
      obtained by using sLORETA. Based on previous research findings, 10 frontal and 6
      parietal regions of interest (ROI) were derived. Alpha asymmetry in the posterior
      cingulate (i.e., BA23 and BA31) was uniquely associated with both POS scores.
      These areas are, hypothetically, part of a complex default-mode neural network
      (DMN). The activity in the DMN usually increases during tasks that invoke self
      referential processing, such as responding to statements describing one's
      personality, attitudes, or preferences. Importantly, the cortical structures
      associated with POS were different from those associated with indicators. Indeed,
      measures of "optimism" failed to maintain a significant correlation with any of
      the previously significant ROI, but "self-esteem" and "life satisfaction"
      revealed robust associations with alpha asymmetry at the precuneus (i.e., BA7),
      after controlling for POS residual scores. IN CONCLUSION: Present findings
      support the assumption that POS is a basic disposition that reflects the
      concerted activity of brain structures that are essential for integrating self
      referential thought and autobiographical memories and for assigning a positive
      valence to one's experience and attitude toward the future.

PMID- 25956139
TI  - Lower concentrations of chemotactic cytokines and soluble innate factors in the
      lower female genital tract associated with the use of injectable hormonal
      contraceptive.
AB  - Progesterone-based injectable hormonal contraceptives (HCs) potentially modulate
      genital barrier integrity and regulate the innate immune environment in the
      female genital tract, thereby enhancing the risk of STIs or HIV infection. We
      investigated the effects of injectable HC use on concentrations of inflammatory
      cytokines and other soluble factors associated with genital epithelial repair and
      integrity. The concentrations of 42 inflammatory, regulatory, adaptive growth
      factors and hematopoietic cytokines, five matrix metalloproteinases (MMPs), and
      four tissue inhibitors of metalloproteinases (TIMPs) were measured in
      cervicovaginal lavages (CVLs) from 64 HIV-negative women using injectable HCs and
      64 control women not using any HCs, in a matched case-control study. There were
      no differences between groups in the prevalence of bacterial vaginosis (BV;
      Nugent score >=7), or common sexually transmitted infections (STIs). In
      multivariate analyses adjusting for condom use, sex work status, marital status,
      BV and STIs, median concentrations of chemokines (eotaxin, MCP-1, MDC), adaptive
      cytokines (IL-15), growth factors (PDGF-AA) and a metalloproteinase (TIMP-2) were
      significantly lower in CVLs from women using injectable HCs than controls. In
      addition, the pro-inflammatory cytokine IL-12p40 and the chemokine fractalkine
      were less likely to have detectable levels in women using injectable HCs compared
      with those not using HCs. We conclude that injectable HC use was broadly
      associated with an immunosuppressive female genital tract innate immune profile.
      While the relationship between injectable HC use and STI or HIV risk is yet to be
      resolved, our data suggest that the effects of injectable HCs were similar in STI
      positive and STI-negative participants. 

PMID- 25956141
TI  - The neural substrates for the different modalities of movement imagery.
AB  - Research highlights that internal visual, external visual and kinesthetic imagery
      differentially effect motor performance (White & Hardy, 1995; Hardy & Callow,
      1999). However, patterns of brain activation subserving these different imagery
      perspectives and modalities have not yet been established. In the current study,
      we applied the Vividness of Movement Imagery Questionnaire-2 (VMIQ-2) to study
      the brain activation underpinning these types of imagery. Participants with high
      imagery ability (using the VMIQ-2) were selected to participate in the study. The
      experimental conditions involved imagining an action (one item from the VMIQ-2)
      using internal visual imagery, external visual imagery, kinesthetic imagery and a
      perceptual control condition involved looking at a fixation cross. The imagery
      conditions were presented using a block design and the participants' brain
      activation was recorded using 3T fMRI. A post-experimental questionnaire was
      administered to test if participants were able to maintain the imagery during the
      task and if they switched between the imagery perspective/modalities. Four
      participants failed to adhere to the imagery conditions, and their data was
      excluded from analysis. As hypothesized, the different perspectives and
      modalities of imagery elicited both common areas of activation (in the right
      supplementary motor area, BA6) and dissociated areas of activation. Specifically,
      internal visual imagery activated occipital, parietal and frontal brain areas
      (i.e., the dorsal stream) while external visual imagery activated occipital
      ventral stream areas and kinesthetic imagery activated caudate and cerebellum
      areas. These results provide the first central evidence for the visual
      perspectives and modalities delineated in the VMIQ-2, and, initial biological
      validity for the VMIQ-2. However, given that only one item from the VMIQ-2 was
      employed, future fMRI research needs to explore all items to further examine
      these contentions. 

PMID- 25956142
TI  - Domain dependent associations between cognitive functioning and regular voluntary
      exercise behavior.
AB  - Regular exercise has often been suggested to have beneficial effects on
      cognition, but empirical findings are mixed because of heterogeneity in sample
      composition (age and sex); the cognitive domain being investigated; the
      definition and reliability of exercise behavior measures; and study design (e.g.,
      observational versus experimental). Our aim was to scrutinize the domain
      specificity of exercise effects on cognition, while controlling for the other
      sources of heterogeneity. In a population based sample consisting of 472 males
      and 668 females (aged 10-86 years old) we administered the Computerized
      Neurocognitive Battery (CNB), which provided accuracy and speed measures of
      abstraction and mental flexibility, attention, working memory, memory (verbal,
      face, and spatial), language and nonverbal reasoning, spatial ability, emotion
      identification, emotion- and age differentiation, sensorimotor speed, and motor
      speed. Using univariate and multivariate regression models, CNB scores were
      associated with participants' average energy expenditure per week (weekly
      METhours), which were derived from a questionnaire on voluntary regular leisure
      time exercise behavior. Univariate models yielded generally positive associations
      between weekly METhours and cognitive accuracy and speed, but multivariate
      modeling demonstrated that direct relations were small and centered around zero.
      The largest and only significant effect size (beta = 0.11, p < 0.001) was on the
      continuous performance test, which measures attention. Our results suggest that
      in the base population, any chronic effects of voluntary regular leisure time
      exercise on cognition are limited. Only a relation between exercise and attention
      inspires confidence.

PMID- 25956143
TI  - Diastolic pressure-volume quotient (DPVQ) as a novel echocardiographic index for
      estimation of LV stiffness in HFpEF.
AB  - BACKGROUND: End-diastolic pressure-volume relationship and LV stiffness, key
      parameter for diagnosing diastolic dysfunction within Heart failure with
      preserved ejection fraction (HFpEF) patients, can be directly obtained only by
      invasive pressure-volume (PV) measurements. Therefore, we aimed to establish
      diastolic pressure-volume quotient (DPVQ), as a new non-invasive parameter for
      estimation of LV stiffness in HFpEF obtained by 3D echocardiography (3DE) and
      tissue Doppler imaging. METHODS: Twenty-three HFpEF patients with suspected
      diastolic dysfunction, scheduled for invasive pressure-volume loop analyses
      obtained by conductance catheterization were included. PV loop measurements were
      compared with simultaneous 3DE full-volume recordings of the LV and tissue
      Doppler measurements for LV diastolic function. LV filling index E/E' was used
      for estimation of diastolic pressure. Single-beat method was performed to
      calculate LV stiffness constant (beta SB). RESULTS: Fourteen of twenty-three
      patients showed increased and 9/23 revealed normal LV stiffness beta. End
      diastolic, end-systolic and stroke volume obtained by 3DE correlated with those
      from PV loop analysis (r = 0.63, r = 0.57 and r = 0.71, respectively). Estimated
      diastolic pressure and DPVQ correlated with invasive measurements (r = 0.81 and r
      = 0.91, both p < 0.001). Accordingly, calculated stiffness constant beta SB
      revealed a significant correlation with invasive determined stiffness coefficient
      beta (r = 0.73, p < 0.001). DPVQ and beta SB correlated with NT-proBNP plasma
      level (r = 0.67 and r = 0.58, both, p < 0.001). CONCLUSION: 3D echocardiography
      allows accurate non-invasive measurements of diastolic pressure-volume quotient
      which correlates with invasive determined LV stiffness in HFpEF.

PMID- 25956144
TI  - New insights into the aquatic photochemistry of fluoroquinolone antibiotics:
      Direct photodegradation, hydroxyl-radical oxidation, and antibacterial activity
      changes.
AB  - The ubiquity and photoreactivity of fluoroquinolone antibiotics (FQs) in surface
      waters urge new insights into their aqueous photochemical behavior. This study
      concerns the photochemistry of 6 FQs: ciprofloxacin, danofloxacin, levofloxacin,
      sarafloxacin, difloxacin and enrofloxacin. Methods were developed to calculate
      their solar direct photodegradation half-lives (td,E) and hydroxyl-radical
      oxidation half-lives (tOH,E) in sunlit surface waters. The td,E values range from
      0.56 min to 28.8 min at 45 degrees  N latitude, whereas tOH,E ranges from 3.24h
      to 33.6h, suggesting that most FQs tend to undergo fast direct photolysis rather
      than hydroxyl-radical oxidation in surface waters. However, a case study for
      levofloxacin and sarafloxacin indicated that the hydroxyl-radical oxidation
      induced risky photochlorination and resulted in multi-degradation pathways, such
      as piperazinyl hydroxylation and clearage. Changes in the antibacterial activity
      of FQs caused by photodegradation in various waters were further examined using
      Escherichia coli, and it was found that the activity evolution depended on
      primary photodegradation pathways and products. Primary intermediates with intact
      FQ nuclei retained significant antibacterial activity. These results are
      important for assessing the fate and risk of FQs in surface waters.

PMID- 25956145
TI  - Stormwater-related transport of the insecticides bifenthrin, fipronil,
      imidacloprid, and chlorpyrifos into a tidal wetland, San Francisco Bay,
      California.
AB  - Suisun Marsh, in northern San Francisco Bay, is the largest brackish marsh in
      California, and provides critical habitat for many fish species. Storm runoff
      enters the marsh through many creeks that drain agricultural uplands and the
      urban areas of Fairfield and Suisun City. Five creeks were sampled throughout a
      major storm event in February 2014, and analyzed for representatives of several
      major insecticide classes. Concentrations were greatest in creeks with urban
      influence, though sampling was done outside of the primary season for
      agricultural pesticide use. Urban creek waters reached maximum concentrations of
      9.9 ng/l bifenthrin, 27.4 ng/l fipronil, 11.9 ng/l fipronil sulfone, 1462 ng/l
      imidacloprid, and 4.0 ng/l chlorpyrifos. Water samples were tested for toxicity
      to Hyalella azteca and Chironomus dilutus, and while few samples caused
      mortality, 70% of the urban creek samples caused paralysis of either or both
      species. Toxic unit analysis indicated that bifenthrin was likely responsible for
      effects to H. azteca, and fipronil and its sulfone degradate were responsible for
      effects to C. dilutus. These results demonstrate the potential for co-occurrence
      of multiple insecticides in urban runoff, each with the potential for toxicity to
      particular species, and the value of toxicity monitoring using multiple species.
      In the channels of Suisun Marsh farther downstream, insecticide concentrations
      and toxicity diminished as creek waters mixed with brackish waters entering from
      San Francisco Bay. Only fipronil and its degradates remained measurable at 1-10
      ng/l. These concentrations are not known to present a risk based on existing
      data, but toxicity data for estuarine and marine invertebrates, particularly for
      fipronil's degradates, are extremely limited.

PMID- 25956146
TI  - In situ treatment of arsenic contaminated groundwater by aquifer iron coating:
      Experimental study.
AB  - In situ arsenic removal from groundwater by an aquifer iron coating method has
      great potential to be a cost effective and simple groundwater remediation
      technology, especially in rural and remote areas where groundwater is used as the
      main water source for drinking. The in situ arsenic removal technology was first
      optimized by simulating arsenic removal in various quartz sand columns under
      anoxic conditions. The effectiveness was then evaluated in an actual high-arsenic
      groundwater environment. The arsenic removal mechanism by the coated iron
      oxide/hydroxide was investigated under different conditions using scanning
      electron microscopy (SEM)/X-ray absorption spectroscopy, electron probe
      microanalysis, and Fourier transformation infrared spectroscopy. Aquifer iron
      coating method was developed via a 4-step alternating injection of oxidant, iron
      salt and oxygen-free water. A continuous injection of 5.0 mmol/L FeSO4 and 2.5
      mmol/L NaClO for 96 h can form a uniform goethite coating on the surface of
      quartz sand without causing clogging. At a flow rate of 7.2 mL/min of the
      injection reagents, arsenic (as Na2HAsO4) and tracer fluorescein sodium to pass
      through the iron-coated quartz sand column were approximately at 126 and 7 column
      pore volumes, respectively. The retardation factor of arsenic was 23.0, and the
      adsorption capacity was 0.11 mol As per mol Fe. In situ arsenic removal from
      groundwater in an aquifer was achieved by simultaneous injections of As(V) and
      Fe(II) reagents. Arsenic fixation resulted from a process of adsorption/co
      precipitation with fine goethite particles by way of bidentate binuclear
      complexes. Therefore, the study results indicate that the high arsenic removal
      efficiency of the in situ aquifer iron coating technology likely resulted from
      the expanded specific surface area of the small goethite particles, which
      enhanced arsenic sorption capability and/or from co-precipitation of arsenic on
      the surface of goethite particles.

PMID- 25956147
TI  - A comparison between monitoring and dispersion modeling approaches to assess the
      impact of aviation on concentrations of black carbon and nitrogen oxides at Los
      Angeles International Airport.
AB  - Aircraft activity and airport operations can increase combustion-related air
      pollutant concentrations, but it is difficult to distinguish aviation emissions
      from traffic and other local sources. Emission inventories are uncertain and
      dispersion models may not capture aircraft plume complexity; ambient monitoring
      data require detailed statistical analyses to extract aviation signals. The goal
      of this study is to compare two modeling approaches including monitoring-based
      regression models and the EDMS/AERMOD dispersion model, informing improvements
      and allowing quantitation of aviation impacts on air quality through multi
      pollutant sensitivity and multi-monitor fate/transport analyses. Aggregate
      concentration comparisons are similar, though diurnal patterns show potential
      weaknesses in near-field dispersion, treatment of overnight conditions, and
      emission inventory accuracy. 

PMID- 25956148
TI  - Seasonal variation of antibiotics concentration in the aquatic environment: a
      case study at Jianghan Plain, central China.
AB  - 25 antibiotics (macrolides, tetracyclines, fluoroquinolones and sulfonamides)
      were detected in swine wastewater, river water, rivulet water and in groundwater
      samples from multi-level monitoring boreholes (with sampling ports, respectively,
      at 10, 25 and 50 m below the land surface) at Jianghan Plain, central China.
      Except swine wastewater, the antibiotic concentrations in groundwater, river and
      rivulet water were higher in spring than those in winter. Nineteen antibiotics
      were detected at 100% frequencies in all kinds of water samples. In groundwater,
      fluoroquinolones and tetracyclines were the predominant antibiotics and the total
      concentrations of 25 antibiotics commonly decreased with the aquifer depth. Most
      groundwater samples collected in spring had high concentrations of norfloxacin,
      with average values of 65.27 ng . L(-1), 37.28 ng . L(-1) and 46.83 ng . L(-1),
      respectively, at 10, 25 and 50 m deep boreholes. By contrast, the concentrations
      of sulfamethazine and erythromycin were rather low in groundwater, but high in
      surface water. Groundwater samples collected from sites close to rivers or
      rivulets had much higher contents of antibiotics than those from other sites,
      indicating that the dominant source of antibiotics in groundwater should be the
      contaminated rivers or rivulets, rather than the scattered pig and poultry farms
      in the study area.

PMID- 25956149
TI  - The Gastric Band That Is Not to Be : Efficacy, Safety and Performance of the
      EasybandTM: a Multicenter Experience.
AB  - BACKGROUND: Access port problems after laparoscopic adjustable gastric banding
      can be significant complications. The EasybandTM is an innovative type of gastric
      band, whose internal diameter can be adjusted by a telemetrically activated
      motor. The aim of this study was to evaluate safety, efficacy and performance of
      the EasybandTM. METHODS: A total of 110 morbidly obese patients were
      prospectively enrolled. The EasybandTM was implanted laparoscopically by
      experienced bariatric surgeons in six different hospital locations. Patient
      characteristics, surgery details, postoperative weight loss, and complications
      were recorded. Follow-up lasted 2 years. RESULTS: Follow-up was completed by 78.2
      % of the patients. Surgeons rated 71 % of each aspect of EasybandTM implantation
      as "easy" or "very easy". Adjustments were successful in 91 % of the attempts.
      One or more adverse events occurred in 79.1 % of the patients. Thirty-six serious
      adverse events were reported, of which 50 % was device-related. One or more
      functional tests failed in 20.9 % of the devices, 8.2 % passed after a repeated
      test. A reintervention was necessary in 15.5 % of the patients. Mean weight loss
      after 2 years was 24.2 +/- 14.0 kg, mean excess weight loss was 46.1 +/- 24 %.
      CONCLUSION: Excess weight loss with the EasybandTM was comparable with other
      gastric banding devices. Adjustment of the device was simple, non-invasive and
      more acceptable to patients than with a standard access port. However, a high
      incidence of device-related problems requiring surgical explantation occurred.
      The EasybandTM represents a major advance in gastric band design, but significant
      technical problems need to be resolved before further implants can be
      recommended.

PMID- 25956150
TI  - Protective Effect of Porcine Cerebral Hydrolysate Peptides on Learning and Memory
      Deficits and Oxidative Stress in Lead-Exposed Mice.
AB  - In this study, lead acetate solution and porcine cerebral hydrolysate peptides
      (PCHPs) were administered to developing mice. Porcine cerebral protein pretreated
      by ultrasound was hydrolyzed with alcalase, and 11 peptide fragments were
      obtained by Matrix-assisted laser desorption ionization-time of flight mass
      spectrometry (MALDI-TOF MS) analysis of PCHPs. Our data showed that PCHPs
      significantly decreased Pb2+-induced spontaneous locomotor activity, latencies to
      reach the platform, and the time in target quadrant. It also decreased the
      accumulation of lead in the blood and brain of Pb2+-exposed developing mice. Co
      administration of PCHPs and dimercaptosuccinic acid (DMSA) did not only reduce
      the accumulation of lead in blood but also increased the absorption of zinc and
      iron in Pb2+-exposed mice. Administration of PCHPs individually significantly
      enhanced hematopoietic parameters compared with the Pb2+-exposed group. PCHPs
      significantly reduced the levels of reactive oxygen species (ROS) and
      malondialdehyde (MDA) but increased glutathione (GSH) content and anti-oxidant
      enzymes and nitric oxide synthase (NOS) activities in Pb2+-exposed brain. Our
      findings suggest that PCHPs have the ability to protect against Pb2+-exposed
      learning and memory deficits and oxidative damage.

PMID- 25956151
TI  - A Home-Based Diaphragmatic Breathing Retraining in Rural Patients With Heart
      Failure.
AB  - Dyspnea limits physical activity and functional status in heart failure patients.
      This feasibility study examined effects of a diaphragmatic breathing retraining
      (DBR) intervention delivered over 8 weeks with follow-up at 5 months. The
      intervention group (n = 18) was trained at baseline and received four telephone
      calls. An attention control group (n = 18) received four telephone calls with
      general health information. Results from linear mixed model analysis with effect
      sizes (eta(2)) showed dyspnea improved in both groups, with little difference
      between groups. Compared with attention alone, the intervention increased
      physical activity (calories expended; eta(2) = .015) and functional status
      (eta(2) = .013) across the 5-month follow-up and increased activity counts at 8
      weeks (eta(2) = .070). This intervention was feasible and demonstrated promising
      effects on activity and function but not by reducing dyspnea. Patients may have
      increased physical activity because of instructions to use DBR during activities
      of daily living. Further exploration of the intervention's underlying
      physiological effect is needed. 

PMID- 25956152
TI  - The Impact of Sexual Media on Second Language Vocabulary Retrieval.
AB  - Both Islam and Christianity warn their adherents not to view or to display
      obscene matter. Aside from religious consequences in the afterlife for such
      behavior, this study was conducted to determine if viewing sexual media has a
      detrimental effect in earthly life. Adolescents (n = 64) 17-22 years were exposed
      to two types of visual stimuli containing sexual or neutral content for 30 min.
      The participants, seated in rooms with comfortable chairs and provided with
      snacks, were shown a selection of 18 German words via a PowerPoint slideshow,
      which included a picture, an audio recording, and the written form of each word.
      The experimental group, which was exposed to arousing visual stimuli with mild
      sexual content (movie trailers, music video clips, and TV commercials),
      remembered significantly fewer words than the control group, which viewed a
      nature documentary without sexual content. T-test scores revealed that exposure
      to sexually arousing media impaired memory for second language (L2) vocabulary.
      Apart from leading to dire consequences in the hereafter, the results of the
      study demonstrate that viewing obscene material also causes harm in this life.

PMID- 25956153
TI  - Parametric time-to-onset models were developed to improve causality assessment of
      adverse drug reactions from antidiabetic drugs.
AB  - OBJECTIVES: The aim of this study was to investigate whether the time to onset
      (TTO) of common adverse drug reactions (ADRs) of antidiabetic drugs could be
      modeled using parametric distributions and whether these TTO distributions were
      dependent on patient characteristics. Furthermore, information relevant for daily
      clinical practice was to be obtained. STUDY DESIGN AND SETTING: We performed an
      exploratory TTO modeling study, using a cohort of diabetes mellitus patients.
      Four parametric distributions (exponential, lognormal, gamma, and Weibull) were
      compared in terms of their goodness of fit. Covariates that could influence the
      TTO were investigated. In addition, TTO mean and median values were summarized
      for use in clinical practice. RESULTS: Overall, the gamma distribution provided
      the best goodness of fit, although differences with the Weibull distribution were
      negligible in some instances. No differences in TTO distributions between
      different antidiabetic drugs for a given ADR were found. The TTO was influenced
      by suspected concomitant medication for metformin-associated diarrhea. Mean and
      median TTO values were similar for different drug-ADR combinations. CONCLUSION:
      Our study shows that the TTO of common ADRs associated with antidiabetic drugs
      can be modeled using the gamma or Weibull distribution. Furthermore, clinically
      relevant information about these ADRs can be obtained.

PMID- 25956154
TI  - Boundaries of confidentiality in nursing care for mother and child in HIV
      programmes.
AB  - BACKGROUND: Confidentiality lies at the core of medical ethics and is the
      cornerstone for developing and keeping a trusting relationship between nurses and
      patients. In the wake of the HIV epidemic, there has been a heightened focus on
      confidentiality in healthcare contexts. Nurses' follow-up of HIV-positive women
      and their susceptible HIV-exposed children has proved to be challenging in this
      regard, but the ethical dilemmas concerning confidentiality that emerge in the
      process of ensuring HIV-free survival of the third party - the child - have
      attracted limited attention. OBJECTIVE: The study explores challenges of
      confidentiality linked to a third party in nurse-patient relationships in a rural
      Tanzanian HIV/AIDS context. STUDY CONTEXT: The study was carried out in rural and
      semi-urban settings of Tanzania where the population is largely agro-pastoral,
      the formal educational level is low and poverty is rife. The HIV prevalence of
      1.5% is low compared to the national prevalence of 5.1%. METHODS: Data were
      collected during 9 months of ethnographic fieldwork and consisted of participant
      observation in clinical settings and during home visits combined with in-depth
      interviews. The main categories of informants were nurses employed in prevention
      of mother-to-child transmission of HIV programmes and HIV-positive women enrolled
      in these programmes. ETHICAL CONSIDERATIONS: Based on information about the study
      aims, all informants consented to participate. Ethical approval was granted by
      ethics review boards in Tanzania and Norway. FINDINGS AND DISCUSSION: The
      material indicates a delicate balance between the nurses' attempt to secure the
      HIV-free survival of the babies and the mothers' desire to preserve
      confidentiality. Profound confidentiality-related dilemmas emerged in actual
      practice, and indications of a lack of thorough consideration of the implication
      of a patient's restricted disclosure came to light during follow-up of the HIV
      positive women and the third party - the child who is at risk of HIV infection
      through mother's milk. World Health Organization's substantial focus on infant
      survival (Millennium Development Goal-4) and the strong calls for disclosure
      among the HIV-positive are reflected on in the discussion.

PMID- 25956155
TI  - Analysis of anticoagulant prescribing in non-valvular atrial fibrillation and
      development of a clinical tool for guiding anticoagulant selection.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia in the United
      States. Traditionally, warfarin has been used to prevent the occurrence of stroke
      in intermediate-to-high risk patients. Target-specific oral anticoagulants
      (TSOACs) have become a favorable alternative; however, recommendations for
      differentiating between the available TSOACs were lacking within the 2012 CHEST
      guidelines. The objective of this retrospective, observational study was to
      identify current anticoagulation prescribing habits in patients admitted with new
      onset AF, and evaluate the appropriateness of discharge therapy based on national
      guidelines. Additionally, a practice guideline was created for use at our
      institution to stratify appropriate use of TSOACs. Patients were included if they
      were at least 18 years old and were admitted with a primary diagnosis of new
      onset, non-valvular AF between July 1, 2012 and June 30, 2013. CHADS2,
      CHA2DS2VASc, and HAS-BLED scores were calculated based on patient data. Between
      July 2012 and June 2013, 143 patients were included in the study. The average
      CHADS2 score was 1.7, the average CHA2DS2VASc score was 3.0, and the average HAS
      BLED score was 2.4. The use of no antithrombotics decreased as the CHA2DS2VASc
      score increased, aspirin use stayed consistent across risk groups, warfarin use
      increased as the CHA2DS2VASc score increased, and TSOAC use decreased with
      increasing CHA2DS2VASc score. A total of 34 % of study patients were prescribed
      inappropriate treatment upon discharge, based on national guidelines. This study
      demonstrated that patients admitted to our hospital were prescribed appropriate
      therapy the majority of the time; however, 34 % were prescribed inadequate
      antithrombotic therapy compared to current practice guidelines given their
      CHA2DS2VASc score. The development of an institution-specific guideline
      stratifying appropriate use of anticoagulation in this population may increase
      adherence to national guideline recommendations. 

PMID- 25956156
TI  - Human milk fortifier with high versus standard protein content for promoting
      growth of preterm infants: A meta-analysis.
AB  - OBJECTIVE: To compare the growth of preterm infants fed standard protein
      fortified human milk with that containing human milk fortifier (HMF) with a
      higher-than-standard protein content. METHODS: Published articles reporting
      randomized controlled trials and prospective observational intervention studies
      listed on the PubMed(r), Embase(r), CINAHL and Cochrane Library databases were
      searched using the keywords 'fortifier', 'human milk', 'breastfeeding', 'breast
      milk' and 'human milk fortifier'. The mean difference with 95% confidence
      intervals was used to compare the effect of HMF with a higher-than-standard
      protein content on infant growth characteristics. RESULTS: Five studies with 352
      infants with birth weight <= 1750 g and a gestational age <= 34 weeks who were
      fed human milk were included in this meta-analysis. Infants in the experimental
      groups given human milk with higher-than-standard protein fortifier achieved
      significantly greater weight and length at the end of the study, and greater
      weight gain, length gain, and head circumference gain, compared with control
      groups fed human milk with the standard HMF. CONCLUSIONS: HMF with a higher-than
      standard protein content can improve preterm infant growth compared with standard
      HMF.

PMID- 25956157
TI  - Private rare deletions in SEC16A and MAMDC4 may represent novel pathogenic
      variants in familial axial spondyloarthritis.
AB  - OBJECTIVE: Axial spondyloarthritis (AxSpA) represents a group of inflammatory
      axial diseases that share common clinical and histopathological manifestations.
      Ankylosing spondylitis (AS) is the best characterised subset of AxSpA, and its
      genetic basis has been extensively investigated. Given that genome-wide
      association studies account for only 25% of AS heritability, the objective of
      this study was to discover rare, highly penetrant genetic variants in AxSpA
      pathogenesis using a well-characterised, multigenerational family. METHODS: HLA
      B*27 genotyping and exome sequencing was performed on DNA collected from
      available family members. Variant frequency was assessed by mining publically
      available datasets and using fragment analysis of unrelated AxSpA cases and
      unaffected controls. Gene expression was performed by qPCR, and protein
      expression was assessed by western blot analysis and immunofluorescence
      microscopy using patient-derived B-cell lines. Circular dichroism spectroscopy
      was performed to assess the impact of discovered variants on secondary structure.
      RESULTS: This is the first report identifying two rare private familial variants
      in a multigenerational AxSpA family, an in-frame SEC16A deletion and an out-of
      frame MAMDC4 deletion. Evidence suggests the causative mechanism for SEC16A
      appears to be a conformational change induced by deletion of three highly
      conserved amino acids from the intrinsically disordered Sec16A N-terminus and RNA
      mediated decay for MAMDC4. CONCLUSIONS: The results suggest that it is the
      presence of rare syntenic SEC16A and MAMDC4 deletions that increases
      susceptibility to AxSpA in family members who carry the HLA-B*27 allele.

PMID- 25956159
TI  - The PRECIS-2 tool: designing trials that are fit for purpose.

PMID- 25956160
TI  - Piperacillin/tazobactam-induced myoclonic jerks in a man with chronic renal
      failure.

PMID- 25956161
TI  - Crescentic Back Cut: A Novel Technique for the Management of Flap/Defect
      Discrepancies in Rotation Flaps.
AB  - BACKGROUND: Facial reconstruction requires the use of various techniques to
      repair cutaneous defects. Sliding flaps, such as advancement and rotation flaps,
      typically result in tension alterations and skin redundancy, necessitating a
      secondary defect. OBJECTIVE: We describe a back cut technique that allows
      minimization of the scar line and appropriate placement of tension vectors in
      certain locations, which we call the crescentic back cut. METHODS: A patient with
      a surgical defect on his preauricular cheek is repaired by use of a rotation flap
      modified with a crescentic back cut. We briefly review the alternative methods
      for management of flap/defect discrepancies in rotation flaps. RESULTS: The
      crescentic back cut is simple to suture, can be adjusted in length and thickness
      to minimize pedicle transection, and keeps the scar short and within the relaxed
      skin tension lines. CONCLUSION: The crescentic back cut is a useful option to
      manage flap/defect discrepancies in rotation flaps.

PMID- 25956158
TI  - Dissecting the Dual Role of AMPK in Cancer: From Experimental to Human Studies.
AB  - The precise role of 5'AMP-activated kinase (AMPK) in cancer and its potential as
      a therapeutic target is controversial. Although it is well established that
      activation of this energy sensor inhibits the main anabolic processes that
      sustain cancer cell proliferation and growth, AMPK activation can confer on
      cancer cells the plasticity to survive under metabolic stress such as hypoxia and
      glucose deprivation, which are commonly observed in fast growing tumors. Thus,
      AMPK is referred to as both a "conditional" tumor suppressor and "contextual"
      oncogene. To add a further layer of complexity, AMPK activation in human cancer
      tissues and its correlation with tumor aggressiveness and progression appears to
      vary in different contexts. The current review discusses the different faces of
      this metabolic regulator, the therapeutic implications of its modulation, and
      provides an overview of the most relevant data available on AMPK activation and
      AMPK-activating drugs in human studies.

PMID- 25956163
TI  - AIM2 co-immunization favors specific multifunctional CD8(+) T cell induction and
      ameliorates coxsackievirus B3-induced chronic myocarditis.
AB  - Coxsackievirus B3 (CVB3) infection can cause acute myocarditis and chronic
      myocarditis, leading to dilated cardiomyopathy (DCM) with no effective
      therapeutic strategy. Therefore, we investigated the potential of absent in
      melanoma 2 (AIM2) to enhance the therapeutic efficacy of DNA vaccine against CVB3
      induced chronic myocarditis. Mice were infected with CVB3 and then intranasally
      immunized with chitosan-pcDNA3.1 (mock), chitosan-pAIM2 (CS-pAIM2), chitosan-pVP1
      (CS-pVP1), or chitosan-pAIM2 plus chitosan-pVP1 (CS-pAIM2/CS-pVP1) at 7, 21, and
      35d. Therapeutic efficacies of various vaccines were evaluated at day 56d.
      Compared with CS-pVP1 immunization, CS-pAIM2/CS-pVP1 co-immunization
      significantly increased survival rate, improved cardiac function, as well as
      decreased myocardial injury and fibrosis, this result indicated that CVB3-induced
      chronic myocarditis was alleviated. CVB3-specific T lymphocyte proliferation and
      cytotoxic T lymphocyte responses of the CS-pAIM2/CS-pVP1 co-immunization group
      were also increased. More interestingly, CS-pAIM2/CS-pVP1 co-immunization could
      facilitate CVB3-specific multifunctional CD8(+) T cell induction in the
      intestinal mucosa, and this induction was closely correlated with myocardial
      scores, this result indicated that CS-pAIM2/CS-pVP1 vaccine exhibits therapeutic
      efficacy by enhancing multifunctional CD8(+) T cells. This study may represent a
      novel therapy for CVB3-induced chronic myocarditis. 

PMID- 25956164
TI  - Thermodynamics of antibody-antigen interaction revealed by mutation analysis of
      antibody variable regions.
AB  - Antibodies (immunoglobulins) bind specific molecules (i.e. antigens) with high
      affinity and specificity. In order to understand their mechanisms of recognition,
      interaction analysis based on thermodynamic and kinetic parameters, as well as
      structure determination is crucial. In this review, we focus on mutational
      analysis which gives information about the role of each amino acid residue in
      antibody-antigen interaction. Taking anti-hen egg lysozyme antibodies and several
      anti-small molecule antibodies, the energetic contribution of hot-spot and non
      hot-spot residues is discussed in terms of thermodynamics. Here, thermodynamics
      of the contribution from aromatic, charged and hydrogen bond-forming amino acids
      are discussed, and their different characteristics have been elucidated. The
      information gives fundamental understanding of the antibody-antigen interaction.
      Furthermore, the consequences of antibody engineering are analysed from
      thermodynamic viewpoints: humanization to reduce immunogenicity and rational
      design to improve affinity. Amino acid residues outside hot-spots in the
      interface play important roles in these cases, and thus thermodynamic and kinetic
      parameters give much information about the antigen recognition. Thermodynamic
      analysis of mutant antibodies thus should lead to advanced strategies to design
      and select antibodies with high affinity. 

PMID- 25956162
TI  - Natural polymorphism S119R of HIV-1 integrase enhances primary INSTI resistance.
AB  - Integrase strand transfer inhibitors (INSTIs), which block proviral DNA
      integration into the host chromosome, are clinically effective against HIV-1
      isolates exhibiting resistance to other classes of antiretroviral agents.
      Although naturally occurring amino acid variation has been less frequently
      observed in the integrase region, the functional constraints of this variation on
      primary INSTI resistance-associated mutations are not fully understood. In the
      present study, we focused on the S119G/R/P/T (S119X) polymorphisms, which are
      frequently observed in HIV-1 sequences derived from clinical specimens (naive,
      n=458, 26%). The frequency of the S119X polymorphism together with Q148H/R (n=8,
      63%) or N155H (n=12, 83%) was relatively high compared with that of naive group.
      Our in vitro assays revealed that S119G/P/T alone exerted no effect on the
      susceptibility to INSTIs, whereas S119R enhanced the level of INSTI resistance
      induced by well-known INSTI resistance-associated mutations (Y143C, Q148H or
      N155H). Notably, the S119R polymorphism contributed to a significant (5.9-fold)
      increase in dolutegravir resistance caused by G140S/Q148H. Analysis of two cases
      of virological failure during raltegravir-based therapy showed that the
      accumulation and the rapid evolution of primary INSTI resistance-associated
      mutations coincided with the S119R mutation. These data highlight the role of the
      S119X polymorphism in INSTI resistance, and this polymorphism might be linked to
      the potential treatment outcome with INSTI-based therapy. 

PMID- 25956165
TI  - Effects of physical activity in telomere length: Systematic review and meta
      analysis.
AB  - The aim of this systematic review is to assess the effects of exercise on
      telomeres length. We searched the following databases: MEDLINE, EMBASE, Cochrane
      Central Register of Controlled Trials (CENTRAL, The Cochrane Library), Scopus,
      LILACS, SPORTDiscus and Web of Science from inception to August 2014. All
      articles that assessed the effects of exercise in telomere length were included
      in this review. The search strategy used the following combinations of terms:
      telomere AND "motor activity" OR exercise OR "physical activity". Two reviewers,
      working independently, screened all titles and abstracts to identify studies that
      could meet inclusion criteria. Whenever possible, and if appropriate, we
      performed a random-effect meta-analysis of study outcomes. Thirty-seven original
      studies were included in this systematic review, including 41,230 participants.
      Twenty articles did not find statistically significant association, whereas 15
      described a positive association. Two papers found an inverted "U" correlation.
      There is a tendency toward demonstrating an effect of exercise on telomere
      length. Few prospective studies were found, many studies did not reach
      statistical significance and there was an important methodological diversity. For
      this reason, a possible significant association between physical activity and
      telomere length remains an open question. 

PMID- 25956166
TI  - Localization and regulation of PML bodies in the adult mouse brain.
AB  - PML is a tumor suppressor protein involved in the pathogenesis of promyelocytic
      leukemia. In non-neuronal cells, PML is a principal component of characteristic
      nuclear bodies. In the brain, PML has been implicated in the control of embryonic
      neurogenesis, and in certain physiological and pathological phenomena in the
      adult brain. Yet, the cellular and subcellular localization of the PML protein in
      the brain, including its presence in the nuclear bodies, has not been
      investigated comprehensively. Because the formation of PML bodies appears to be a
      key aspect in the function of the PML protein, we investigated the presence of
      these structures and their anatomical distribution, throughout the adult mouse
      brain. We found that PML is broadly expressed across the gray matter, with the
      highest levels in the cerebral and cerebellar cortices. In the cerebral cortex
      PML is present exclusively in neurons, in which it forms well-defined nuclear
      inclusions containing SUMO-1, SUMO 2/3, but not Daxx. At the ultrastructural
      level, the appearance of neuronal PML bodies differs from the classic one, i.e.,
      the solitary structure with more or less distinctive capsule. Rather, neuronal
      PML bodies have the form of small PML protein aggregates located in the close
      vicinity of chromatin threads. The number, size, and signal intensity of neuronal
      PML bodies are dynamically influenced by immobilization stress and seizures. Our
      study indicates that PML bodies are broadly involved in activity-dependent
      nuclear phenomena in adult neurons.

PMID- 25956167
TI  - Surgeon-tailored polypropylene mesh as a tension-free vaginal tape-obturator
      versus original TVT-O for the treatment of female stress urinary incontinence: a
      long-term comparative study.
AB  - INTRODUCTION AND HYPOTHESIS: The objective of the study was to compare the safety
      and efficacy of surgeon-tailored polypropylene mesh (STM) through tension-free
      vaginal tape-obturator (TVT-O) versus original TVT-O in the treatment of stress
      urinary incontinence (SUI) aiming to decrease the cost of treatment. This is
      important in developing countries due to limited health care resources. METHODS:
      A retrospective cohort study was done at the Urology and Gynecology Departments
      (dual-center), Cairo University from May 2007 to June 2010. Women evaluated by
      cough stress test, Stress and Urge Incontinence and Quality of Life Questionnaire
      (SUIQQ), maximum flow rate (Qmax), and abdominal leak point pressure (ALPP) with
      follow-up for at least 48 months were included. Patients with post-void residual
      urine > 100 ml, bladder capacity < 300 ml, or impaired compliance were excluded.
      The effect of different factors on outcome was compared between both groups pre-
      and postoperatively using the paired t, Wilcoxon signed rank, McNemar, chi
      square, Fisher's exact, independent t, or Mann-Whitney tests. RESULTS: STM and
      TVT-O were inserted in 79 and 66 women, respectively. Intrinsic sphincter
      deficiency, ALPP, previous surgeries, associated urgency, urgency urinary
      incontinence (UUI), and prolapse were comparable in both groups. Operative
      duration was longer in STM by 10 min. No significant difference was found between
      both groups in complications (p = 0.462), cure (p = 0.654), and different indices
      of SUIQQ. In STM, 74 (93 %) were cured and 3 (4 %) improved, while SUI persisted
      in 2 (2 %) patients. In TVT-O, 59 (89 %) were cured and 4 (6 %) improved, while
      failure was detected in 3 (4 %) patients. CONCLUSIONS: The 5-year outcome is
      comparable between STM and TVT-O. Furthermore, STM is more economical due to our
      resterilizable modified helical passers and the cheap polypropylene mesh.

PMID- 25956168
TI  - Clinical research in paediatrics: what can we do?

PMID- 25956169
TI  - Better therapies for children: a worldwide search for needed human resources.
AB  - A point has been reached in the pursuit of optimal prescribing for infants,
      children and youth where global deficiencies in inter-professional communication
      are presenting a substantial barrier to progress. In an effort to remedy this
      situation, the International Alliance for Better Medicines for Children (IABMC)
      is seeking to create an international registry of engaged essential personnel. An
      open invitation is extended to all those who wish to partner with others in
      actively addressing the pressing global health challenge represented by gaps in
      the evidence base supporting safe and effective drug therapy for children of all
      ages. Respondents are invited to complete a brief survey at:
      https://www.surveymonkey.com/s/H3GKSHP . 

PMID- 25956170
TI  - Metaphyseal tibial level (MTL) screws: a modified percutaneous technique for
      lateral plateau depression fractures.
AB  - INTRODUCTION: Lateral tibial plateau fractures are more frequent than medial
      fractures, and those with articular depression are particularly challenging
      because of high displacement risk. To prevent secondary subsidence, the gold
      standard is raft screws with a periarticular or anti-glide plate. Graft is used
      to fill the metaphyseal defect created by reduction in the depressed fragment. We
      present a case of Schatzker II fracture managed in a complete percutaneous
      fashion, with a new combined technique of raft screws and interference screw used
      as a support. CASE REPORT: A 51-year-old female sustained a Schatzker II tibial
      plateau fracture. Based on pre-operative CT, direction of reduction force to
      apply was drawn on coronal and sagittal cuts. OPERATIVE TECHNIQUE: Under
      fluoroscopic control, the split component of the fracture was reduced. The
      cortical window was then drilled in the lateral cortex, and a K wire advanced
      under the depressed fragment under fluoroscopic guidance. After fragment
      reduction with a bone impacter, internal fixation was completed by percutaneous
      introduction of two subchondral cortical screws. A bioabsorbable interference
      screw was then introduced in the impacter tunnel to support impacted bone under
      the reduced articular surface. Finally, a cortical screw was introduced, from
      anterior to posterior to prevent screw cut-out. CONCLUSION: The combination of
      subchondral screws in a jail technique with a bioabsorbable interference screw
      that we named metaphyseal tibia level (MTL) screw technique is, to our knowledge,
      not described. The MTL screw promises to be a true percutaneous reduction and
      fixation technique for Schatzker II and III fractures in patients with reasonable
      bone quality.

PMID- 25956171
TI  - Anogenital HIV RNA in Thai men who have sex with men in Bangkok during acute HIV
      infection and after randomization to standard vs. intensified antiretroviral
      regimens.
AB  - INTRODUCTION: HIV transmission risk is highest during acute HIV infection (AHI).
      We evaluated HIV RNA in the anogenital compartment in men who have sex with men
      (MSM) during AHI and compared time to undetectable HIV RNA after three-drug
      versus five-drug antiretroviral therapy (ART) to understand risk for onward HIV
      transmission. METHODS: MSM with AHI (n=54) had blood, seminal plasma and anal
      lavage collected for HIV RNA at baseline, days 3 and 7, and weeks 2, 4, 12 and
      24. Data were compared between AHI stages: 1 (fourth-generation antigen-antibody
      combo immunoassay [IA]-, third-generation IA-, n=15), 2 (fourth-generation IA+,
      third-generation IA-, n=9) and 3 (fourth-generation IA+, third-generation IA+,
      western blot-/indeterminate, n=30) by randomization to five-drug
      (tenofovir+emtricitabine+efavirenz+raltegravir+maraviroc, n=18) versus three-drug
      (tenofovir+emtricitabine+efavirenz, n=18) regimens. RESULTS: Mean age was 29
      years and mean duration since HIV exposure was 15.4 days. Mean baseline HIV RNA
      was 5.5 in blood, 3.9 in seminal plasma and 2.6 log10 copies/ml in anal lavage
      (p<0.001). Blood and seminal plasma HIV RNA were higher in AHI Stage 3 compared
      to Stage 1 (p<0.01). Median time from ART initiation to HIV RNA <50 copies/ml was
      60 days in blood, 15 days in seminal plasma and three days in anal lavage.
      Compared with the three-drug ART, the five-drug ART had a shorter time to HIV RNA
      <1500 copies/ml in blood (15 vs. 29 days, p=0.005) and <50 copies/ml in seminal
      plasma (13 vs. 24 days, p=0.048). CONCLUSIONS: Among MSM with AHI, HIV RNA was
      highest in blood, followed by seminal plasma and anal lavage. ART rapidly reduced
      HIV RNA in all compartments, with regimen intensified by raltegravir and
      maraviroc showing faster HIV RNA reductions in blood and seminal plasma.

PMID- 25956173
TI  - Is bad luck the main cause of cancer?
AB  - A recent study reports that the log lifetime incidence rate across a selection of
      31 cancer types is highly correlated with the log of the estimated tissue
      specific lifetime number of stem cell divisions. This observation, which
      underscores the importance of errors in DNA replication, has been viewed as
      implying that most cancers arise through unavoidable bad luck, leading to the
      suggestion that research efforts should focus on early detection, rather than
      etiology or prevention. We argue that three statistical issues can, if ignored,
      lead analysts to incorrect conclusions. Statistics for traffic fatalities across
      the United States provide an example to demonstrate those inferential pitfalls.
      While the contribution of random cellular events to disease is often
      underappreciated, the role of chance is necessarily difficult to quantify. The
      conclusion that most cases of cancer are fundamentally unpreventable because they
      are the result of chance is unwarranted. 

PMID- 25956172
TI  - Practical problems with clinical guidelines for breast cancer prevention based on
      remaining lifetime risk.
AB  - BACKGROUND: Clinical guidelines for breast cancer chemoprevention and MRI
      screening involve estimates of remaining lifetime risk (RLR); in the United
      States, women with an RLR of 20% or higher meet "high-risk" criteria for MRI
      screening. METHODS: We prospectively followed 1764 women without breast cancer to
      compare the RLRs and 10-year risks assigned by the risk models International
      Breast Cancer Intervention Study (IBIS) and Breast and Ovarian Analysis of
      Disease Incidence and Carrier Estimation Algorithm (BOADICEA) and to compare both
      sets of model-assigned 10-year risks to subsequent incidence of breast cancer in
      the cohort. We used chi-square statistics to assess calibration and the area
      under the receiver operating characteristic curve (AUC) to assess discrimination.
      All statistical tests are two-sided. RESULTS: The models classified different
      proportions of women as high-risk (IBIS = 59.3% vs BOADICEA = 20.1%) using the
      RLR threshold of 20%. The difference was smaller (IBIS = 52.9% vs BOADICEA =
      43.2%) using a 10-year risk threshold of 3.34%. IBIS risks (mean = 4.9%) were
      better calibrated to observed breast cancer incidence (5.2%, 95% confidence
      interval (CI) = 4.2% to 6.4%) than were those of BOADICEA (mean = 3.7%) overall
      and within quartiles of model risk (P = .20 by IBIS and P = .07 by BOADICEA).
      Both models gave similar discrimination, with AUCs of 0.67 (95% CI = 0.61 to
      0.73) using IBIS and 0.68 (95% CI = 0.62 to 0.74) using BOADICEA. Model
      sensitivities at thresholds for a 20% false-positive rate were also similar, with
      41.8% using IBIS and 38.0% using BOADICEA. CONCLUSION: RLR-based guidelines for
      high-risk women are limited by discordance between commonly used risk models.
      Guidelines based on short-term risks would be more useful, as models are
      generally developed and validated under a short fixed time horizon (<=10 years).

PMID- 25956174
TI  - Helicobacter pylori vesicles carrying CagA localize in the vicinity of cell-cell
      contacts and induce histone H1 binding to ATP in epithelial cells.
AB  - Helicobacter pylori produces outer membrane vesicles (OMV), delivering bacterial
      substances including the oncogenic cytotoxin-associated CagA protein to their
      surroundings. We investigated the effects of H. pylori OMV carrying CagA (OMV
      CagA) on cell junctions and ATP-binding proteome of epithelial monolayers, using
      proteomics, mass spectrometry and imaging. OMV-CagA localized in close vicinity
      of ZO-1 tight junction protein and induced histone H1 binding to ATP. We suggest
      the expression of novel events in the interactions between H. pylori OMV and
      epithelia, which may have an influence on host gene transcription and lead to
      different outcomes of an infection and development of cancer. 

PMID- 25956175
TI  - A multicopper oxidase contributes to the copper tolerance of Brucella melitensis
      16M.
AB  - Copper is a potent antimicrobial agent. Multiple mechanisms of copper tolerance
      are utilized by some pathogenic bacteria. BMEII0580, which is significantly
      similar to the multicopper oxidase from Escherichia coli, was predicted to be the
      probable blue copper protein YacK precursor in Brucella melitensis 16M, and was
      designated as Brucella multicopper oxidase (BmcO). A bioinformatics analysis
      indicated that the typical motifs of multicopper oxidases are present in BmcO.
      BmcO, the expression of which was up-regulated by copper, could catalyze the
      oxidation of 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS),
      dimethoxyphenol (DMP) and para-phenylenediamine (pPD), which are widely used as
      substrates for multicopper oxidase. Additionally, BmcO exhibited ferroxidase
      activity, which indicated that it might play an important role in the Fe(2+)
      uptake of B. melitensis. Importantly, the mutant strain 16MDeltabmcO was more
      sensitive to copper than the wild-type strain B. melitensis 16M as well as its
      complementation strain 16MDeltabmcO(bmcO). The infection assays of cells showed
      that similar bacterial numbers of B. melitensis 16M, 16MDeltabmcO and
      16MDeltabmcO(bmcO) strains were recovered from the infected macrophages. This
      result indicated that BmcO was not essential for B. melitensis intracellular
      growth. In conclusion, our results confirm that BmcO is a multicopper oxidase and
      contributes to the copper tolerance of B. melitensis 16M. 

PMID- 25956176
TI  - Correction for Zhang et al., The conserved SOCS box motif in suppressors of
      cytokine signaling binds to elongins B and C and may couple bound proteins to
      proteasomal degradation.

PMID- 25956177
TI  - Correction for Han et al., Quantum dot/antibody conjugates for in vivo cytometric
      imaging in mice.

PMID- 25956178
TI  - Correction for Godar et al., Actor-specific contributions to the deforestation
      slowdown in the Brazilian Amazon.

PMID- 25956179
TI  - Quantifying ligand-cell interactions and determination of the surface
      concentrations of ligands on hydrogel films: The measurement challenge.
AB  - Hydrogels are extensively studied for biomaterials application as they provide
      water swollen noninteracting matrices in which specific binding motifs and enzyme
      sensitive degradation sites can be incorporated to tailor cell adhesion,
      proliferation, and migration. Hydrogels also serve as excellent basis for surface
      modification of biomaterials where interfacial characteristics are decisive for
      implant success or failure. However, the three-dimensional nature of hydrogels
      makes it hard to distinguish between the bioactive ligand density at the hydrogel
      cell interface that is able to interact with cells and the ligands that are
      immobilized inside the hydrogel and not accessible for cells. Here, the authors
      compare x-ray photoelectron spectrometry (XPS), time-of-flight secondary ion mass
      spectroscopy (ToF-SIMS), enzyme linked immunosorbent assay (ELISA), and the
      correlation with quantitative cell adhesion using primary human dermal
      fibroblasts (HDF) to gain insight into ligand distribution. The authors show that
      although XPS provides the most useful quantitative analysis, it lacks the
      sensitivity to measure biologically meaningful concentrations of ligands.
      However, ToF-SIMS is able to access this range provided that there are clearly
      distinguishable secondary ions and a calibration method is found. Detection by
      ELISA appears to be sensitive to the ligand density on the surface that is
      necessary to mediate cell adhesion, but the upper limit of detection coincides
      closely with the minimal ligand spacing required to support cell proliferation.
      Radioactive measurements and ELISAs were performed on amine reactive well plates
      as true 2D surfaces to estimate the ligand density necessary to allow cell
      adhesion onto hydrogel films. Optimal ligand spacing for HDF adhesion and
      proliferation on ultrathin hydrogel films was determined as 6.5 +/- 1.5 nm.

PMID- 25956180
TI  - Development of cup shaped microneedle array for transdermal drug delivery.
AB  - Microneedle technology is one of the attractive methods in transdermal drug
      delivery. However, the clinical applications of this method are limited owing to:
      complexity in the preparation of multiple coating solutions, drug leakage while
      inserting the microneedles into the skin and the outer walls of the solid
      microneedle can hold limited quantity of drug. Here, the authors present the
      fabrication of an array of rectangular cup shaped silicon microneedles, which
      provide for reduced drug leakage resulting in improvement of efficiency of drug
      delivery and possibility of introducing multiple drugs. The fabricated solid
      microneedles with rectangular cup shaped tip have a total height of 200 MUm.
      These cup shaped tips have dimensions: 60 * 60 MUm (length * breadth) with a
      depth of 60 MUm. The cups are filled with drug using a novel in-house built drop
      coating system. Successful drug dissolution was observed when the coated
      microneedle was used on mice. Also, using the above method, it is possible to
      fill the cups selectively with different drugs, which enables simultaneous
      multiple drug delivery.

PMID- 25956181
TI  - Investigation of the antimicrobial activity at safe levels for eukaryotic cells
      of a low power atmospheric pressure inductively coupled plasma source.
AB  - Low power atmospheric pressure inductively coupled thermal plasma sources
      integrated with a quenching device (cold ICP) for the efficient production of
      biologically active agents have been recently developed for potential biomedical
      applications. In the present work, in vitro experiments aimed at assessing the
      decontamination potential of a cold ICP source were carried out on bacteria
      typically associated with chronic wounds and designed to represent a realistic
      wound environment; further in vitro experiments were performed to investigate the
      effects of plasma-irradiated physiological saline solution on eukaryotic cells
      viability. A thorough characterization of the plasma source and process, for what
      concerns ultraviolet (UV) radiation and nitric oxide production as well as the
      variation of pH and the generation of nitrates and nitrites in the treated liquid
      media, was carried out to garner fundamental insights that could help the
      interpretation of biological experiments. Direct plasma treatment of bacterial
      cells, performed at safe level of UV radiation, induces a relevant
      decontamination, both on agar plate and in physiological saline solution, after
      just 2 min of treatment. Furthermore, the indirect treatment of eukaryotic cells,
      carried out by covering them with physiological saline solution irradiated by
      plasma, in the same conditions selected for the direct treatment of bacterial
      cells does not show any noticeable adverse effect to their viability. Some
      considerations regarding the role of the UV radiation on the decontamination
      potential of bacterial cells and the viability of the eukaryotic ones will be
      presented. Moreover, the effects of pH variation, nitrate and nitrite
      concentrations of the plasma-irradiated physiological saline solution on the
      decontamination of bacterial suspension and on the viability of eukaryotic cells
      subjected to the indirect treatment will be discussed. The obtained results will
      be used to optimize the design of the ICP source for an effective production of
      reactive species, while keeping effluent temperature and UV radiation at values
      compatible with biomedical treatments.

PMID- 25956182
TI  - Towards quantitative diagnosis of ossicular fixation: Measurement of stapes
      fixations using magnetically driven ossicles in human temporal bones.
AB  - CONCLUSION: Information on the degree of stapes fixation can be found by
      measuring the ratio of stapes to umbo and stapes to incus velocity. OBJECTIVES:
      To evaluate a method of quantifying ossicular fixation in an ear with elevated
      tympanic membrane. METHOD: Measurements were made on four fresh-frozen human
      temporal bones. After elevating the tympanic membrane, a small magnet was
      attached to the manubrium and an electromagnetic excitation coil was used to
      vibrate the ossicles. The vibration response of the umbo, the tip of the incus
      long process, and the posterior crus of the stapes were measured before and after
      partially fixing the footplate with luting cement. RESULTS: The velocities at the
      different measurement points were unequally affected by the fixation. The
      difference in the velocity ratio between different points provides an indication
      of the degree of footplate fixation.

PMID- 25956183
TI  - Hydrogen sulfide improves resuscitation via non-hibernatory mechanisms in a
      porcine shock model.
AB  - BACKGROUND: Hydrogen sulfide (H2S) has been demonstrated to induce a "suspended
      animation-like" state in rodent models by reversible inhibition of cellular
      respiration and marked metabolic suppression and has been proposed as a potential
      pharmacologic adjunct to resuscitation from shock states. There are few data
      currently available about the mechanisms and efficacy of H2S in larger animals or
      humans. We examined H2S as a pharmacologic adjunct to resuscitation in a porcine
      model of severe traumatic shock. METHODS: Twenty-one adult swine were assigned to
      three study arms: sham, H2S, and saline vehicle controls (SC). All pigs underwent
      laparotomy and instrumentation, and the two study arms then underwent a 35%
      controlled hemorrhage followed by 50 min of truncal ischemia via aortic cross
      clamp. H2S (5 mg/kg) or saline was administered immediately before reperfusion,
      followed by 6 h of resuscitation. Resuscitation requirements, laboratory
      parameters, end-organ histology, and inflammatory product gene expression (by
      reverse transcription-polymerase chain reaction) were measured and compared
      between groups. RESULTS: All animals survived to the 6-h postresuscitation time
      point. Both treatment arms demonstrated severe shock characterized by fluid and
      vasopressor requirements, metabolic acidosis, and hypotension compared with sham
      animals. Animals treated with H2S demonstrated significantly lower resuscitative
      requirements (total epinephrine 727 versus 3052 MUg; P < 0.05), decreased fluid
      requirements, and lower serum lactate levels (7 versus 10 mmol/L) versus SC.
      Cardiac output was slightly decreased with H2S treatment but all other
      hemodynamic and metabolic parameters were equivalent between H2S and C groups.
      Serum liver and kidney biomarkers were unchanged, but administration of H2S was
      associated with a significant improvement in histopathologic liver and kidney
      injury scores compared with SC (both P < 0.05). Both study groups demonstrated
      significantly increased gene expression of hypoxia-inducible factor 1alpha and
      nitric oxide synthase (endogenous nitric oxide synthase, inducible nitric oxide
      synthase [iNOS]2, iNOS3) relative to sham animals. However, H2S was associated
      with increased expression of hypoxia-inducible factor 1alpha and decreased iNOS2
      levels compared with SC. CONCLUSIONS: Administration of H2S in a large-animal
      model of severe traumatic shock resulted in a significant decrease in
      resuscitative requirements, decreased metabolic acidosis, and less end-organ
      histologic injury compared with standard resuscitation. H2S did not induce
      profound metabolic suppression as seen in rodents, and appears to have
      alternative mechanisms of action in large animals.

PMID- 25956184
TI  - Matrix metalloproteinases-9 deficiency impairs liver regeneration through
      epidermal growth factor receptor signaling in partial hepatectomy mice.
AB  - BACKGROUND: Liver regeneration is a complex process regulated by many complex
      mechanisms involving cytokines, growth factors, metabolic networks, and so forth.
      Previous investigations have demonstrated that matrix metalloproteinase-9 (MMP-9)
      is an essential factor in liver regeneration. The present study aimed to explore
      the role of MMP-9 in epidermal growth factor receptor (EGFR) signaling and
      related proliferation signaling factors in a mouse partial hepatectomy (PH)
      model. MATERIALS AND METHODS: MMP-9 knockout (KO) and wild-type mice were used to
      establish the PH model. Liver regeneration was analyzed based on proliferation
      cell nuclear antigen immunohistochemistry and liver weight to body weight ratio.
      Also, EGFR ligands, EGFR, and downstream factors were measured by quantitative
      real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and
      Western blot. RESULTS: MMP-9 KO mice showed a delayed hepatic regenerative
      response after PH. EGFR ligands, including heparin-binding epidermal growth
      factor and amphiregulin, were expressed at significantly lower levels between
      days 1 and 3 posthepatectomy in MMP-9 KO mice. MMP-9 KO mice also inhibited and
      delayed EGFR activation after PH. After PH, the expression of STAT3, NF-kappaB,
      and cyclinD1, all downstream of EGFR, was similar to EGFR activation.
      CONCLUSIONS: Our data provide new evidence supporting a critical role of MMP-9 in
      liver regeneration after PH through activation of EGFR signaling.

PMID- 25956185
TI  - GOBF-ARMA based model predictive control for an ideal reactive distillation
      column.
AB  - This paper discusses the control of an ideal reactive distillation column (RDC)
      using model predictive control (MPC) based on a combination of deterministic
      generalized orthonormal basis filter (GOBF) and stochastic autoregressive moving
      average (ARMA) models. Reactive distillation (RD) integrates reaction and
      distillation in a single process resulting in process and energy integration
      promoting green chemistry principles. Improved selectivity of products, increased
      conversion, better utilization and control of reaction heat, scope for difficult
      separations and the avoidance of azeotropes are some of the advantages that
      reactive distillation offers over conventional technique of distillation column
      after reactor. The introduction of an in situ separation in the reaction zone
      leads to complex interactions between vapor-liquid equilibrium, mass transfer
      rates, diffusion and chemical kinetics. RD with its high order and nonlinear
      dynamics, and multiple steady states is a good candidate for testing and
      verification of new control schemes. Here a combination of GOBF-ARMA models is
      used to catch and represent the dynamics of the RDC. This GOBF-ARMA model is then
      used to design an MPC scheme for the control of product purity of RDC under
      different operating constraints and conditions. The performance of proposed
      modeling and control using GOBF-ARMA based MPC is simulated and analyzed. The
      proposed controller is found to perform satisfactorily for reference tracking and
      disturbance rejection in RDC. 

PMID- 25956186
TI  - Studies on adsorption, reaction mechanisms and kinetics for photocatalytic
      degradation of CHD, a pharmaceutical waste.
AB  - The photocatalytic degradation of chlorhexidine digluconate (CHD), a disinfectant
      and topical antiseptic and adsorption of CHD catalyst surface in dark condition
      has been studied. Moreover, the value of kinetic parameters has been measured and
      the effect of adsorption on photocatalysis has been investigated here.
      Substantial removal was observed during the photocatalysis process, whereas 40%
      removal was possible through the adsorption route on TiO2 surface. The parametric
      variation has shown that alkaline pH, ambient temperature, low initial substrate
      concentration, high TiO2 loading were favourable, though at a certain
      concentration of TiO2 loading, photocatalytic degradation efficiency was found to
      be maximum. The adsorption study has shown good confirmation with Langmuir
      isotherm and during the reaction at initial stage, it followed pseudo-first-order
      reaction, after that Langmuir Hinshelwood model was found to be appropriate in
      describing the system. The present study also confirmed that there is a
      significant effect of adsorption on photocatalytic degradation. The possible
      mechanism for adsorption and photocatalysis has been shown here and process
      controlling step has been identified. The influences of pH and temperature have
      been explained with the help of surface charge distribution of reacting particles
      and thermodynamic point of view respectively. 

PMID- 25956187
TI  - Maintenance Therapy With Cetuximab Every Second Week in the First-Line Treatment
      of Metastatic Colorectal Cancer: The NORDIC-7.5 Study by the Nordic Colorectal
      Cancer Biomodulation Group.
AB  - BACKGROUND: In the NORDIC-7.5 trial, how cetuximab might safely and conveniently
      be added to an intermittent treatment strategy in patients with prospectively
      selected Kirsten rat sarcoma viral oncogene homolog wild type (KRASwt) metastatic
      colorectal cancer (mCRC) was investigated. Patients were treated in a multicenter
      phase II trial with cetuximab in combination with the Nordic bolus FLOX
      (oxaliplatin, 5-fluorouracil, and folinic acid) for 4 months followed by
      maintenance cetuximab. PATIENTS AND METHODS: Patients had KRASwt, nonresectable
      mCRC, no previous chemotherapy, and Eastern Cooperative Group performance status
      of 0 to 2. Patients received 8 courses of Nordic FLOX (oxaliplatin 85 mg/m(2)
      over 1 hour on day 1, and 5-fluorouracil 500 mg/m(2) as a bolus injection,
      followed 30 minutes later with bolus folinic acid 60 mg/m(2) on days 1 and 2).
      Cetuximab was administered every 2 weeks at a dose of 500 mg/m(2) for 16 weeks
      followed by cetuximab as maintenance therapy until disease progression. RESULTS:
      Between July 2008 and September 2010, 152 KRASwt patients were included. The
      response rate was 62% (95% confidence interval [CI], 54%-69%), median progression
      free survival was 8.0 months (95% CI, 7.5-8.9) and median overall survival was
      23.2 (95% CI, 18.1-27.4) months. Twenty-one patients (14%) had later R0-resection
      of metastasis. FLOX with cetuximab was reintroduced in 47 of 85 patients (55%).
      The most common Grade 3/4 nonhematologic adverse events were diarrhea in 14
      patients (9%), skin rash in 13 patients (9%), infection without neutropenia in 11
      patients (7%), and fatigue in 11 patients (7%). CONCLUSION: In a prospectively
      selected KRASwt population, biweekly cetuximab was safely integrated in an
      intermittent chemotherapy strategy and might have added to a longer chemotherapy
      free interval. However, the combination of biweekly cetuximab with chemotherapy
      needs to be validated in trials using FOLFOX (oxaliplatin, fluorouracil, and
      leucovorin) or FOLFIRI (irinotecan, fluorouracil, and leucovorin).

PMID- 25956188
TI  - Aesthetic emotions to art - What they are and what makes them special: Comment on
      "The quartet theory of human emotions: An integrative and neurofunctional model"
      by S. Koelsch et al.

PMID- 25956189
TI  - Quality of life and symptom assessment in randomized clinical trials of bladder
      cancer: A systematic review.
AB  - OBJECTIVES: Patient-reported outcomes (PRO) help patients, caretakers,
      clinicians, and policy makers make informed decisions regarding treatment
      effectiveness. Our objective was to assess the quality of PRO reporting and
      methodological strengths and weaknesses in randomized controlled trials (RCT) in
      bladder cancer. METHODS: A systematic literature search of bladder cancer RCT
      published between January 2004 and March 2014 was performed. Relevant studies
      were evaluated using a predetermined extraction form that included trial
      demographics, clinical and PRO characteristics, and standards of PRO reporting
      based on recommendations of the International Society for Quality of Life
      Research. RESULTS: In total, 9 RCTs enrolling 1,237 patients were evaluated. All
      studies were in patients with nonmetastatic disease. In 5 RCTs, a PRO was the
      primary end point. Most RCTs did not report the mode of administration of the PRO
      instrument or the methods of collecting data. No RCT addressed the statistical
      approaches for missing data. CONCLUSIONS: We found that few RCTs in bladder
      cancer report PRO as an outcome. Efforts to expand PRO reporting to more RCTs and
      improve the quality of PRO reporting according to recognized standards are
      necessary for facilitating clinical decision making.

PMID- 25956190
TI  - Physiological correlates of the flow experience during computer game playing.
AB  - Flow is the subjective experience of effortless attention, reduced self
      awareness, and enjoyment that typically occurs during optimal task performance.
      Previous studies have suggested that flow may be associated with a non-reciprocal
      coactivation of the sympathetic and parasympathetic systems and, on a cortical
      level, with a state of hypofrontality and implicit processing. Here, we test
      these hypotheses, using the computer game TETRIS as model task. The participants
      (n=77) played TETRIS under three conditions that differed in difficulty
      (Easy<Optimal<Difficult). Cardiac and respiratory activities, and the average
      oxygenation changes of the prefrontal cortex were measured continuously with
      functional near infrared spectroscopy (fNIRS) during performance. The Optimal
      condition was characterized by the highest levels of state flow, positive affect,
      and effortless attention. The associations between self-reported psychological
      flow and physiological measures were investigated using a series of repeated
      measures linear mixed model analyses. The results showed that higher flow was
      associated with larger respiratory depth and lower LF. The higher respiratory
      depth during high flow is indicative of a more relaxed state with an increased
      parasympathetic activity, and thus provides partial support for the main
      hypotheses. There was no association between frontal cortical oxygenation and
      flow, even at liberal thresholds; i.e. we found no support that flow is related
      to a state of hypofrontality. 

PMID- 25956191
TI  - Phonetic training and non-native speech perception--New memory traces evolve in
      just three days as indexed by the mismatch negativity (MMN) and behavioural
      measures.
AB  - Language-specific, automatically responding memory traces form the basis for
      speech sound perception and new neural representations can also evolve for non
      native speech categories. The aim of this study was to find out how a three-day
      phonetic listen-and-repeat training affects speech perception, and whether it
      generates new memory traces. We used behavioural identification, goodness rating,
      discrimination, and reaction time tasks together with mismatch negativity (MMN)
      brain response registrations to determine the training effects on native Finnish
      speakers. We trained the subjects the voicing contrast in fricative sounds.
      Fricatives are not differentiated by voicing in Finnish, i.e., voiced fricatives
      do not belong to the Finnish phonological system. Therefore, they are extremely
      hard for Finns to learn. However, only after three days of training, the native
      Finnish subjects had learned to perceive the distinction. The results show
      striking changes in the MMN response; it was significantly larger on the second
      day after two training sessions. Also, the majority of the behavioural indicators
      showed improvement during training. Identification altered after four sessions of
      training and discrimination and reaction times improved throughout training.
      These results suggest remarkable language-learning effects both at the perceptual
      and pre-attentive neural level as a result of brief listen-and-repeat training in
      adult participants. 

PMID- 25956192
TI  - Human epidermal growth factor receptor-2 antibodies enhance the specificity and
      anticancer activity of light-sensitive doxorubicin-labeled liposomes.
AB  - Antibody-mediated targeting therapy has been successful in treating patients with
      cancers by improving the specificity and clinical efficacy. In this study, we
      developed a human epidermal growth factor receptor-2 (HER2) antibody-conjugated
      drug delivery system, using near-infrared (NIR) light-sensitive liposomes
      containing doxorubicin (DOX) and hollow gold nanospheres (HAuNS). We demonstrated
      the specific binding and selective toxicity of the system to HER2-positive tumor
      cells in co-cultures of HER2-positive and -negative cells. Furthermore, the HER2
      antibody-mediated delivery of targeted liposomes was confirmed in a double-tumor
      model in nude mice simultaneously bearing HER2-positive and -negative tumors.
      This induced a >2-fold increased accumulation in the tumors with positive
      expression of HER2 than that with non-targeted liposomes (no HER2-antibody
      conjugation). The combination of targeted liposomes with NIR laser irradiation
      had significant antitumor activity in vivo with the tumor inhibition efficiency
      up to 92.7%, attributed to the increased accumulation in tumors and the double
      efficacy of photothermal-chemotherapy. Moreover, targeted liposomes did not cause
      systemic toxicity during the experiment period, attributable to the reduced dose
      of DOX, the decreased accumulation of liposomes in normal tissues, and the low
      irradiation power. The targeted liposomes provide a multifunctional
      nanotechnology platform for antibody-mediated delivery, light-trigged drug
      release, and combined photothermal-chemotherapy, which may have potential in the
      clinical treatment of cancer. 

PMID- 25956193
TI  - A facile synthesis of versatile Cu2-xS nanoprobe for enhanced MRI and infrared
      thermal/photoacoustic multimodal imaging.
AB  - A novel type of intelligent nanoprobe by using single component of Cu2-xS for
      multimodal imaging has been facilely and rapidly synthesized in scale via thermal
      decomposition followed by biomimetic phospholipid modification, which endows them
      with uniform and small nanoparticle size (ca.15 nm), well phosphate buffer saline
      (PBS) dispersity, high stability, and excellent biocompatibility. The as
      synthesized Cu2-xS nanoprobes (Cu2-xS NPs) are capable of providing contrast
      enhancement for T1-weighted magnetic resonance imaging (MRI), as demonstrated by
      the both in vitro and in vivo imaging investigations for the first time. In
      addition, due to their strong near infrared (NIR) optical absorption, they can
      also serve as a candidate contrast agent for enhanced infrared
      thermal/photoacoustic imaging, to meet the shortfalls of MRI. Hence,
      complementary and potentially more comprehensive information can be acquired for
      the early detection and accurate diagnosis of cancer. Furthermore, negligible
      systematic side effects to the blood and tissue were observed in a relatively
      long period of 3 months. The distinctive multimodal imaging capability with
      excellent hemo/histocompatibility of the Cu2-xS NPs could open up a new molecular
      imaging possibility for detecting and diagnosing cancer or other diseases in the
      future.

PMID- 25956194
TI  - pH-responsive scaffolds generate a pro-healing response.
AB  - A principal challenge in wound healing is a lack of cell recruitment, cell
      infiltration, and vascularization, which occurs in the absence of temporal and
      spatial cues. We hypothesized that a scaffold that expands due to local changes
      in pH may alter oxygen and nutrient transport and the local cell density, leading
      to enhanced cell deposition and survival. In this study, we present a pH
      responsive scaffold that increases oxygen transport, as confirmed by our finite
      element model analysis, and cell proliferation relative to a non-responsive
      scaffold. In vivo, responsive scaffolds induce a pro-healing gene expression
      profile indicative of enhanced angiogenesis, granulation tissue formation, and
      tissue remodeling. Scaffolds that stretch in response to their environment may be
      a hallmark for tissue regeneration.

PMID- 25956195
TI  - Purification and characterization of a novel antibacterial peptide from black
      soldier fly (Hermetia illucens) larvae.
AB  - In this study, we induced and purified a novel antimicrobial peptide exhibiting
      activity against Gram-positive bacteria from the immunized hemolymph of Hermetia
      illucens larvae. The immunized hemolymph was extracted, and the novel defensin
      like peptide 4 (DLP4) was purified using solid-phase extraction and reverse-phase
      chromatography. The purified DLP4 demonstrated a molecular weight of 4267 Da, as
      determined using the matrix-assisted laser desorption/ionization-time-of-flight
      (MALDI-TOF) method. From analysis of DLP4 by N-terminal amino acid sequencing
      using Edman degradation, combined with MALDI-TOF and rapid amplification of cDNA
      ends-polymerase chain reaction (RACE-PCR), the amino acid sequence of the mature
      peptide was determined to be ATCDLLSPFKVGHAACAAHCIARGKRGGWCDKRAVCNCRK. In NCBI
      BLAST, the amino acid sequence of DPL4 was found to be 75% identical to the
      Phlebotomus duboscqi defensin. Analysis of the minimal inhibitory concentration
      (MIC) revealed that DLP4 have antibacterial effects against Gram-positive
      bacteria including methicillin-resistant Staphylococcus aureus (MRSA). The
      expression of DLP4 transcripts in several tissues after bacterial challenge was
      measured by quantitative real-time PCR. Expression of the DLP4 gene hardly
      occurred throughout the body before immunization, but was mostly evident in the
      fat body after immunization.

PMID- 25956196
TI  - Cloning and characterization of two lipopolysaccharide-binding
      protein/bactericidal permeability-increasing protein (LBP/BPI) genes from the sea
      cucumber Apostichopus japonicus with diversified function in modulating ROS
      production.
AB  - Lipopolysaccharide-binding protein and bactericidal permeability-increasing
      protein (LBP/BPI) play crucial role in modulating cellular signals in response to
      Gram-negative bacteria infection. In the present study, two isoforms of LBP/BPI
      genes (designated as AjLBP/BPI1 and AjLBP/BPI2, respectively) were cloned from
      the sea cucumber Apostichopus japonicus by RACE approach. The full-length cDNAs
      of AjLBP/BPI1 and AjLBP/BPI2 were of 1479 and 1455 bp and encoded two secreted
      proteins of 492 and 484 amino acid residues, respectively. Signal peptide, two
      BPI/LBP/CETP and one central domain were totally conserved in the deduced amino
      acid of AjLBP/BPI1 and AjLBP/BPI2. Phylogentic analysis further supported that
      AjLBP/BPI1 and AjLBP/BPI2 belonged to new members of invertebrates LBP/BPI
      family. Spatial expression analysis revealed that both AjLBP/BPI1 and AjLBP/BPI2
      were ubiquitously expressed in all examined tissues with the larger magnitude in
      AjLBP/BPI1. The Vibrio splenfidus challenge and LPS stimulation could
      significantly up-regulate the mRNA expression of both AjLBP/BPI1 and AjLBP/BPI2,
      with the increase of AjLBP/BPI2 expression occurred earlier than that of
      AjLBP/BPI1. More importantly, we found that LPS induced ROS production was
      markedly depressed after AjLBP/BPI1 knock-down, but there was no significant
      change by AjLBP/BPI2 silencing. Consistently, the expression level of
      unclassified AjToll, not AjTLR3, was tightly correlated with that of AjLBP/BPI1.
      Silencing the AjToll also depressed the ROS production in the cultured
      coelomocytes. All these results indicated that AjLBP/BPI1 and AjLBP/BPI2 probably
      played distinct roles in bacterial mediating immune response in sea cucumber, and
      AjLBP/BPI1 depressed coelomocytes ROS production via modulating AjToll cascade.

PMID- 25956197
TI  - Conserved and narrow temperature limits in alpine insects: Thermal tolerance and
      supercooling points of the ice-crawlers, Grylloblatta (Insecta: Grylloblattodea:
      Grylloblattidae).
AB  - For many terrestrial species, habitat associations and range size are dependent
      on physiological limits, which in turn may influence large-scale patterns of
      species diversity. The temperature range experienced by individuals is considered
      to shape the breadth of the thermal niche, with species occupying temporally
      and/or geographically stable climates tolerating a narrow temperature range. High
      elevation environments experience large temperature fluctuations, with frequent
      periods below 0  degrees C, but Grylloblatta (Grylloblattodea: Grylloblattidae)
      occupy climatically stable microhabitats within this region. Here we test
      critical thermal limits and supercooling points for five Grylloblatta populations
      from across a large geographic area, to examine whether the stable microhabitats
      of this group are associated with a narrow thermal niche and assess their
      capacity to tolerate cold conditions. Thermal limits are highly conserved in
      Grylloblatta, despite substantial genetic divergence among populations spanning
      1500 m elevation and being separated by over 500 km. Further, Grylloblatta show
      exceptionally narrow thermal limits compared to other insect taxa with little
      capacity to improve cold tolerance via plasticity. In contrast, upper thermal
      limits were significantly depressed by cold acclimation. Grylloblatta maintain
      coordinated movement until they freeze, and they die upon freezing. Convergence
      of the critical thermal minima, supercooling point and lower lethal limits point
      to adaptation to a cold but, importantly, constant thermal environment. These
      physiological data provide an explanation for the high endemism and patchy
      distribution of Grylloblatta, which relies on subterranean retreats to
      accommodate narrow thermal limits. These retreats are currently buffered from
      temperature fluctuations by snow cover, and a declining snowpack thus places
      Grylloblatta at risk of exposure to temperatures beyond its tolerance capacity.

PMID- 25956199
TI  - Role of SNARE proteins in tumourigenesis and their potential as targets for novel
      anti-cancer therapeutics.
AB  - The function of soluble N-ethylmaleimide-sensitive factor attachment protein
      receptors (SNAREs) in cellular trafficking, membrane fusion and vesicle release
      in synaptic nerve terminals is well characterised. Recent studies suggest that
      SNAREs are also important in the control of tumourigenesis through the regulation
      of multiple signalling and transportation pathways. The majority of published
      studies investigated the effects of knockdown/knockout or overexpression of
      particular SNAREs on the normal function of cells as well as their dysfunction in
      tumourigenesis promotion. SNAREs are involved in the regulation of cancer cell
      invasion, chemo-resistance, the transportation of autocrine and paracrine
      factors, autophagy, apoptosis and the phosphorylation of kinases essential for
      cancer cell biogenesis. This evidence highlights SNAREs as potential targets for
      novel cancer therapy. This is the first review to summarise the expression and
      role of SNAREs in cancer biology at the cellular level, their interaction with
      non-SNARE proteins and modulation of cellular signalling cascades. Finally, a
      strategy is proposed for developing novel anti-cancer therapeutics using targeted
      delivery of a SNARE-inactivating protease into malignant cells. 

PMID- 25956198
TI  - Physiological responses of emerald ash borer larvae to feeding on different ash
      species reveal putative resistance mechanisms and insect counter-adaptations.
AB  - Emerald ash borer, Agrilus planipennis Fairmaire, an Asian wood-boring beetle,
      has devastated ash (Fraxinus spp.) trees in North American forests and landscapes
      since its discovery there in 2002. In this study, we collected living larvae from
      EAB-resistant Manchurian ash (Fraxinus mandschurica), and susceptible white
      (Fraxinus americana) and green (Fraxinus pennsylvanica) ash hosts, and quantified
      the activity and production of selected detoxification, digestive, and
      antioxidant enzymes. We hypothesized that differences in larval physiology could
      be used to infer resistance mechanisms of ash. We found no differences in
      cytochrome P450, glutathione-S-transferase, carboxylesterase, sulfotransferase,
      and tryptic BApNAase activities between larvae feeding on different hosts.
      Despite this, Manchurian ash-fed larvae produced a single isozyme of low
      electrophoretic mobility that was not produced in white or green ash-fed larvae.
      Additionally, larvae feeding on white and green ash produced two serine protease
      isozymes of high electrophoretic mobility that were not observed in Manchurian
      ash-fed larvae. We also found lower activity of beta-glucosidase and higher
      activities of monoamine oxidase, ortho-quinone reductase, catalase, superoxide
      dismutase, and glutathione reductase in Manchurian ash-fed larvae compared to
      larvae that had fed on susceptible ash. A single isozyme was detected for both
      catalase and superoxide dismutase in all larval groups. The activities of the
      quinone-protective and antioxidant enzymes are consistent with the resistance
      phenotype of the host species, with the highest activities measured in larvae
      feeding on resistant Manchurian ash. We conclude that larvae feeding on
      Manchurian ash could be under quinone and oxidative stress, suggesting these may
      be potential mechanisms of resistance of Manchurian ash to EAB larvae, and that
      quinone-protective and antioxidant enzymes are important counter-adaptations of
      larvae for dealing with these resistance mechanisms. 

PMID- 25956200
TI  - Effect of uterine lavage on neutrophil counts in postpartum dairy cows.
AB  - Subclinical endometritis affects approximately 30% of lactating dairy cows,
      causing significant economic losses to the dairy industry. Yet, there is no
      efficient treatment available for this condition. The present study examines the
      effect of uterine lavage in clinically normal cows with sterile saline solution
      at 30 days in milk (DIM) on the percentage of polymorphonuclear cells (PMNs)
      detected with endometrial cytology as an indicator of subclinical endometritis.
      It was hypothesized uterine lavage would be a technique to reduce the number of
      PMNs in the uterus, and hence be beneficial for cows affected by subclinical
      endometritis. Cytology samples were taken by low-volume flushing from 50 Holstein
      Friesian cows on 30 and 40 DIM. On Day 30, cows were clinically examined and
      randomly assigned into a treatment and control group. In the treatment group, the
      cytology sampling on Day 30 was immediately followed by uterine lavage with 500
      600 mL of sterile physiological saline (35-40 degrees C). Cytology sampling was
      repeated in all cows at 40 DIM. Lactation numbers >2, peripheral progesterone
      concentrations >1 ng/mL and uterine lavage at 30 DIM all were significantly
      associated with lesser PMN percentages at 40 DIM (P=0.0041; 0.0187 and 0.0043,
      respectively). Uterine lavage might, therefore, be a useful and practical method
      to decrease the number of PMNs in the uterus of cattle. Results from the current
      study can be used as preliminary data for designing in depth therapeutic
      protocols for treatment of subclinical endometritis in cattle.

PMID- 25956201
TI  - Chemically assisted somatic cell nuclear transfer without micromanipulator in the
      goat: effects of demecolcine, cytochalasin-B, and MG-132 on the efficiency of a
      manual method of oocyte enucleation using a pulled Pasteur pipette.
AB  - The present study aimed to facilitate widespread application of a previously
      described manual method of somatic cell nuclear transfer (SCNT) by investigating
      the effects of demecolcine (a microtubule-depolymerizing chemical), cytochalasin
      B (a microfilament-depolymerizing chemical: 2.5MUg/ml for 15min) and MG-132 (a
      proteasome inhibitor chemical) on the (i) incidence of cytoplasmic protrusion of
      MII chromosomes, (ii) improvement of manual oocyte enucleation, and (iii) in
      vitro and in vivo developmental competence of SCNT embryos in the goat. Following
      in vitro maturation, around 65% of goat oocytes contained a characteristic
      cytoplasmic protrusion of MII-chromosomes. Treatment with demecolcine (0.4MUg/ml
      for 30min) significantly increased this rate to 92.2+/-4.5%. Treatment with MG
      132 (2MUM for 30min) could not improve this rate when used alone (61.4+/-11.5%),
      but when combined with demecolcine (86.4+/-8.1%). Treatment with cytochalasin-B
      completely suppressed this rate whenever used, either alone (7.7+/-5.1%) or in
      combination with demecolcine (3.9+/-1.3%). In a direct comparison, there was no
      significant difference in quantity and quality of embryos propagated by the
      manual vs. micromanipulation-based methods of SCNT (cleavage: 85.3+/-4.5 vs.
      89.5+/-8.9%, blastocyst: 19.5+/-4.3 vs. 24.3+/-4.4%, grade 1 and 2 blastocyst:
      33.8+/-7.1 vs. 29.5+/-6.3%, total cell count: 125+/-11.1 vs. 122+/-10.5,
      respectively). Furthermore, development to live kids at term was not significant
      between the two SCNT methods. From both technical and economical points of view,
      the overall in vitro and in vivo efficiency of this manual method of SCNT proved
      it a simple, fast and efficient alternative for large scale production of cloned
      goats. 

PMID- 25956202
TI  - Effect of a kneeling chair on lumbar curvature in patients with low back pain and
      healthy controls: A pilot study.
AB  - BACKGROUND: The concept of an ideal sitting posture is often used in practice but
      lacks a basis in evidence. OBJECTIVE: We designed a cross-sectional, comparative,
      matched study to determine the effects of chair and posture on lumbar curvature
      in 10 patients with chronic non-specific low back pain (CLBP; mean pain duration
      24 +/- 18 months) and 10 healthy matched controls. METHODS: Pelvic incidence,
      sacral slope and lumbar curvature were measured on computed radiographs by 2
      blinded clinicians for subjects in 2 postures (upright vs slumped sitting) and on
      2 chairs (usual flat chair vs kneeling chair). RESULTS: The reliability of
      measures was excellent (intraclass correlation coefficient>0.9). As hypothesized,
      the expected sacral slope and lumbar lordosis changed between standing and
      sitting on a kneeling chair as compared with a usual chair (P<0.0001) and less in
      patients than controls (P=0.046) for lordosis only. In addition, as expected,
      changes were more pronounced with slumped than upright sitting (P<0.0001). An
      interaction between chairs and postures for lumbar lordosis (P=0.02) indicated
      more pronounced effects of the chair in slumped sitting. Therefore, lumbar
      lordosis was reduced less when sitting on a kneeling chair as compared with a
      usual chair. CONCLUSIONS: Although healthy subjects showed more reduction in
      lordosis between standing and sitting, the chair effect was found in both CLBP
      patients and healthy subjects.

PMID- 25956203
TI  - Perceptions of links between family history and the experience of illness among
      brain-damaged patients and their families.

PMID- 25956204
TI  - Speech myoclonus due to probable pregabalin adverse drug-reaction.

PMID- 25956205
TI  - Levodopa-induced lateral jaw deviation dystonia.

PMID- 25956206
TI  - Is climate change a threat for water uses in the Mediterranean region? Results
      from a survey at local scale.
AB  - Water scarcity and water security are linked, not only through the direct effects
      of water shortages on each water users' access to water, but also because of
      water conflicts generated. Climate change is predicted to raise temperatures in
      the Mediterranean region and reduce rainfall, leading to a reduction in water
      yield and possibly worsening the situation of water resource shortages that
      Mediterranean regions are already experiencing. In its dissemination strategy,
      the EU FP7 CLIMB project addressed water security threats through an analysis of
      water uses and water use rivalries within a few target catchments distributed
      over the Mediterranean region. The present work explores whether climate change
      is locally perceived by stakeholders (water users and managers) as a key issue
      for their water uses and water security. Individual interviews, meetings, and
      compilation of questionnaires were conducted at five sites located in the
      Mediterranean region. The methodology permitted an analysis of water use and its
      evolution in the water management context, an identification of the state of
      awareness of local stakeholders and of the pressures on water use and water use
      rivalries, and a prioritization of water uses. Currently, the main response to
      increasing water demand in the Mediterranean region, while not yet considering
      climate change as a driving force, is a progressive externalization of water
      resources, with limits represented by national borders and technological
      possibilities. Overall, 'climate change' was not mentioned by stakeholders during
      both interviews and in answers to the questionnaires. Even the prospect of
      decreasing precipitation was not considered a relevant or threatening issue in
      the coming 20years. This confirms the need to continue all efforts to disseminate
      the state of knowledge on climate change impacts in the Mediterranean region,
      such as water scarcity, especially to local water managers, as initiated by
      various research programs of the European Commission. 

PMID- 25956207
TI  - Complexity of the cell-cell interactions in the innate immune response after
      cerebral ischemia.
AB  - In response to brain ischemia a cascade of signals leads to the activation of the
      brain innate immune system and to the recruitment of blood borne derived cells to
      the ischemic tissue. These processes have been increasingly shown to play a role
      on stroke pathogenesis. Here, we discuss the key features of resident microglia
      and different leukocyte subsets implicated in cerebral ischemia with special
      emphasis of neutrophils, monocytes and microglia. We focus on how leukocytes are
      recruited to injured brain through a complex interplay between endothelial cells,
      platelets and leukocytes and describe different strategies used to inhibit their
      recruitment. Finally, we discuss the possible existence of different leukocyte
      subsets in the ischemic tissue and the repercussion of different myeloid
      phenotypes on stroke outcome. The knowledge of the nature of these heterogeneous
      cell-cell interactions may open new lines of investigation on new therapies to
      promote protective immune responses and tissue repair after cerebral ischemia or
      to block harmful responses. This article is part of a Special Issue entitled SI:
      Cell Interactions In Stroke. 

PMID- 25956208
TI  - EUROCOURSE lessons learned from and for population-based cancer registries in
      Europe and their programme owners: Improving performance by research programming
      for public health and clinical evaluation.
AB  - Population-based cancer registries (CRs) in Europe have played a supportive,
      sometimes guiding, role in describing geographic variation of cancer epidemics
      and comparisons of oncological practice and preventive interventions since the
      1950s for all types of cancer, separate and simultaneously. This paper deals with
      historical and longitudinal developments of the roughly 160 CRs and their
      programme owners (POs) that emerged since 1927 and accelerating since the late
      70s especially in southern and continental Europe. About 40 million newly
      diagnosed patients were recorded since the 1950s out of a total of 100 million of
      whom almost 20 million are still alive and about 10% annually dying from cancer.
      The perception of unity in diversity and suboptimal comparability in performance
      and governance of CRs was confirmed in the EUROCOURSE (EUROpe against cancer:
      Optimisation of the Use of Registries for Scientific Excellence in research)
      European Research Area (ERA)-net coordination FP7 project of the European
      Commission (EU) which explored best practices, bottlenecks and future challenges
      of CRs. Regional oncologic and public health changes but also academic embedding
      of CRs varied considerably, although Anno 2012 optimal cancer surveillance indeed
      demanded intensive collaboration with professional and institutional stakeholders
      in two major areas (public health and clinical research) and five minor
      overlapping cancer research domains: aetiologic research, mass screening
      evaluation, quality of care, translational prognostics and survivorship. Each of
      these domains address specific study questions, mixes of disciplines,
      methodologies, additional data-sources and funding mechanisms. POs tended to
      become more and more public health institutes, Health ministries, but also
      comprehensive cancer centres and cancer societies through more and more funding
      at project or programme basis. POs were not easy to pin down because of their
      multiple, sometimes competitive (funding) obligations and increasing complexity
      of cancer surveillance. But they also rather seemed to need guiding principles
      for Governance of 'their' CR(s) as well as to appreciate value of collaborative
      research in Europe and shield CRs against unreasonable data protection in case of
      linkages. Despite access to specialised care related shortcomings, especially of
      survival cohort studies, European databases for studies of incidence and survival
      (such as ACCIS and EUREG on the one hand and EUROCARE and RARECARE on the other
      hand) have proved to be powerful means for comparative national or regional
      cancer surveillance. Pooling of comparable data will exhibit much instructive
      variation in time and place. If POs of CRs would consider multinational European
      studies of risk and prognosis of cancer more to serve their own regional or
      national interest, then progress in this field will accelerate and lead to more
      consistent funding from the EU. The current 20 million cancer survivors and their
      care providers are likely to appreciate more feedback. CONCLUSION: Most CRs
      remain uniquely able to report on progress against cancer by studies of variation
      in incidence (in time and place), detection and survival, referral and treatment
      patterns and their (side) effects in unselected patients, the latter especially
      in the (very) elderly. Programming and profiling its multiple and diverse
      clinical and prevention research is likely to promote involvement of public
      health and clinical stakeholders with a population-based research interest,
      increasingly patient groups and licensed 'buyers' of oncologic services.

PMID- 25956209
TI  - Impact of early tumour shrinkage and resection on outcomes in patients with wild
      type RAS metastatic colorectal cancer.
AB  - BACKGROUND: Tumour shrinkage (TS) increases the possibility of resection in
      metastatic colorectal cancer (mCRC) and may improve tumour-related symptoms. Here
      we report prespecified secondary response-related end-points and exploratory
      TS/resection outcomes for patients with RAS wild-type (WT) tumours (no mutations
      in KRAS/NRAS exons 2/3/4) from the PRIME study (NCT00364013). METHODS: PRIME was
      a randomised phase 3 study comparing first-line panitumumab+FOLFOX4 versus
      FOLFOX4 in mCRC patients. Tumour response analyses were conducted to compare
      response rates and their impact on survival outcomes. RESULTS: Overall, 505
      patients had RAS WT mCRC. More patients receiving panitumumab+FOLFOX4 versus
      FOLFOX4 had ?30% (59% versus 38%; P<0.001) or ?20% (72% versus 57%; P<0.001) TS
      at week 8 (early TS); consistent TS benefits were observed over the first
      ~40weeks of treatment. Objective response rate (P=0.003), duration of response
      (P=0.0027), depth of response (P=0.0149), progression-free survival (PFS;
      P=0.0015) and overall survival (OS; P=0.0057) were improved in the
      panitumumab+FOLFOX4 group. Both early TS and resection were associated with
      improved PFS and OS. 2-year OS rates for patients who did (n=64) versus did not
      (n=441) undergo resection were 88% versus 40%; 2-year OS rates for patients who
      did (n=45) versus did not (n=460) undergo complete resection were 96% versus 41%.
      CONCLUSIONS: More patients receiving panitumumab+FOLFOX4 versus FOLFOX4 had ?30%
      or ?20% TS at week 8; PFS and OS were also improved with panitumumab+FOLFOX4. The
      clinical value of achieving early TS in mCRC warrants further investigation.

PMID- 25956211
TI  - Duodenal gastrointestinal stromal tumor: From clinicopathological features to
      surgical outcomes.
AB  - Duodenal gastrointestinal tumors represent an extremely rare subset of stromal
      tumors arising from interstitial cells of Cajal. In the last 30 years the
      comprehension of the pathophysiology and natural history of this previously
      misunderstood clinical entity, in association with developments in endoscopy,
      imaging technology, and immunohistochemistry has resulted in novel diagnostic and
      treatment approaches. This is a comprehensive review of the current data of the
      literature on the various aspects of the diagnosis and treatment of these tumors.
      The duodenum is the less commonly involved site for these tumors in the digestive
      tract. Endoscopy and computed tomography can usually establish the diagnosis,
      confirmed by immunohistochemical staining and occasionally molecular genetic
      analysis. Endoscopic ultrasound with fine needle aspiration has been recently
      found to be the gold diagnostic standard with high sensitivity and specificity
      rates, diagnosing GIST in up to 80% of patients. Due to the complex anatomy of
      the pancreatico-duodenal region optimal therapeutic strategy of duodenal GISTs
      are challenging. Nevertheless surgical resection with microscopically clear
      resection margins seems to be the only potentially curative treatment for non
      metastatic primary GISTs of the duodenum. Imatinib mesylate plays a key role in
      the management of GISTs both as neoadjuvant therapy and in patients with
      recurrent and metastatic disease. Meanwhile, the advances in the comprehension of
      the pathophysiology and natural history of this previously misunderstood clinical
      entity as well as the treatment of these tumors may render feasible, in the near
      future, the advent of newer and more effective treatment options. 

PMID- 25956210
TI  - Elevated intraocular pressure induces Rho GTPase mediated contractile signaling
      in the trabecular meshwork.
AB  - Rho GTPase regulated contractile signaling in the trabecular meshwork (TM) has
      been shown to modulate aqueous humor (AH) outflow and intraocular pressure (IOP).
      To explore whether elevated IOP, a major risk factor for primary open angle
      glaucoma (POAG) influences Rho GTPase signaling in the TM, we recorded AH outflow
      in enucleated contralateral porcine eyes perfused for 4-5 h at either 15 mm or 50
      mm Hg pressure. After perfusion, TM tissue extracted from perfused eyes was
      evaluated for the activation status of Rho GTPase, myosin light chain (MLC),
      myosin phosphatase target substrate 1 (MYPT1), myristoylated alanine-rich C
      kinase substrate (MARCKS) and paxillin. Eyes perfused at 50 mm Hg exhibited a
      significant decrease in AH outflow facility compared with those perfused at 15 mm
      Hg. Additionally, TM tissue from eyes perfused at 50 mm Hg revealed significantly
      increased levels of activated RhoA and phosphorylated MLC, MYPT1, MARCKS and
      paxillin compared to TM tissue derived from eyes perfused at 15 mm Hg. Taken
      together, these observations indicate that elevated IOP-induced activation of Rho
      GTPase-dependent contractile signaling in the TM is associated with increased
      resistance to AH outflow through the trabecular pathway, and demonstrate the
      sensitivity of Rho GTPase signaling to mechanical force in the AH outflow
      pathway. 

PMID- 25956212
TI  - Squamous cell carcinoma of the rectum: The treatment paradigm.
AB  - PURPOSE: This study was planned to clarify the optimal treatment for squamous
      cell carcinoma of the rectum, an histological entity extremely rare. METHODS: Ten
      patients with histologically proven squamous cell carcinoma of the rectum were
      treated with concomitant radiochemotherapy. Radiation therapy was delivered with
      a 3Dconformational multiple field technique to a dose ranging from 45 to 76.5 Gy,
      with 6-15 MV energy photons. Chemotherapy consisted of an antimetabolite drug in
      association with mitomycin C or oxaliplatin. Overall survival and disease free
      survival were considered in months from the end of the concomitant treatment.
      RESULTS: All patients completed programmed radiochemotherapy treatment but two
      patients were excluded to the analysis. Six patients (75%) presented negative
      biopsy 6 months after the end of radiochemotherapy. Seven patients (87.5%) showed
      a tumour regression after initial treatment. Only 1 patient underwent salvage
      surgery. Considering a mean follow-up of 41.75 months, 7 patients are still
      disease free survivors. Only 1 patient developed local recurrence at 6 months and
      he died 14 months after abdomino-perineal resection. CONCLUSION: Primary radio
      chemotherapy, with a curative intent, could be considered the treatment modality
      of choice for squamous carcinoma of the rectum.

PMID- 25956213
TI  - Brain glycogen supercompensation after different conditions of induced
      hypoglycemia and sustained swimming in rainbow trout (Oncorhynchus mykiss).
AB  - Brain glycogen is depleted when used as an emergency energy substrate. In
      mammals, brain glycogen levels rebound to higher than normal levels after a
      hypoglycemic episode and a few hours after refeeding or administration of
      glucose. This phenomenon is called glycogen supercompensation. However, this
      mechanism has not been investigated in lower vertebrates. The aim of this study
      was therefore to determine whether brain glycogen supercompensation occurs in the
      rainbow trout brain. For this purpose, short-term brain glucose and glycogen
      contents were determined in rainbow trout after being subjected to the following
      experimental conditions: i) a 5-day or 10-day fasting period and refeeding; ii) a
      single injection of insulin (4 mg kg(-1)) and refeeding; and iii) sustained
      swimming and injection of glucose (500 mg kg(-1)). Food deprivation during the
      fasting periods and insulin administration both induced a decrease in glucose and
      glycogen levels in the brain. However, only refeeding after 10 days of fasting
      significantly increased the brain glycogen content above control levels, in a
      clear short-term supercompensation response. Unlike in mammals, prolonged
      exercise did not alter brain glucose or glycogen levels. Furthermore, brain
      glycogen supercompensation was not observed after glucose administration in fish
      undergoing sustained swimming. To our knowledge, this is the first study
      providing direct experimental evidence for the existence of a short-term glycogen
      supercompensation response in a teleost brain, although the response was only
      detectable after prolonged fasting.

PMID- 25956214
TI  - Immune-mediated leukopenia due to Chlamydophila pneumoniae pneumonia.

PMID- 25956215
TI  - False pulmonary embolism on computed tomography angiography in two patients with
      thoracic anatomic distortion.

PMID- 25956216
TI  - Serologic profile and clinical markers of Sjogren syndrome in patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: The aim of this study was to evaluate the clinical relevance of
      rheumatoid factor (RF) and antibodies against cyclic citrullinated peptides (anti
      CCP) in patients with Sjogren syndrome (SS) secondary to rheumatoid arthritis
      (RA). METHODS: The study included 118 individuals, and the subjects were divided
      into three groups: rheumatoid arthritis (RA; n = 46), RA with secondary Sjogren
      syndrome (RA/SS; n = 20) and healthy controls (C; n = 52). Clinical and
      laboratory characteristics, including ocular, oral, and serum markers, anti-CCP,
      and rheumatoid factor (RF), were compared in addition to biopsy of labial minor
      salivary glands. RESULTS: The RA group exhibited unstimulated salivary flow rate,
      and Schirmer test results were similar to those for C and higher than those for
      RA/SS (P < .05). Furthermore, the frequency of xerophthalmia and xerostomia was
      similar among the RA and C groups, and much higher in the RA/SS group (P < .05).
      Anti-CCP positivity and serum levels were similar in both RA groups, irrespective
      of SS diagnosis (RA * RA/SS; P > .05). RF presented a similar frequency and serum
      level between the RA and RA/SS groups (P > .05). CONCLUSIONS: Secondary SS seems
      to be a cluster of oral and ocular symptoms among patients with RA. Anti-CCP and
      RF are not relevant to evaluate the presence of SS among these patients.

PMID- 25956217
TI  - Quality of life in patients with oral potentially malignant disorders: a
      systematic review.
AB  - There is a paucity of literature on quality of life (QoL) in patients with oral
      potentially malignant disorders (OPMDs) despite these conditions being relatively
      common, chronic, and potentially debilitating. The aim of this paper is to
      systematically review the literature on QoL in patients with OPMDs. A search from
      electronic databases PUBMED, MEDLINE, and CINAHL Plus retrieved 180 titles after
      removing duplicates, and a further 4 papers were identified by hand searching.
      Study of the abstracts identified 25 truly relevant articles, which were studied
      in full. Of these, 14 met our strict inclusion criteria. Most studies were cross
      sectional; most were from Europe and have evaluated QoL in patients with oral
      lichen planus (OLP). The findings differ but, overall, do not provide evidence
      that patients with OPMDs have a poorer QoL compared with healthy patients.
      Several things may explain this apparently surprising conclusion. First, the
      quality of most articles was moderate or weak; second, most studies assessed QoL
      only in patients with OLP and cannot be generalized to all patients with OPMDs;
      last, direct comparisons between patients with OPMD and healthy controls were
      rarely included. The validity of the QoL instrument used for patients with OLP
      was frequently inadequate. 

PMID- 25956218
TI  - Second opinion reporting in head and neck pathology: the pattern of referrals and
      impact on final diagnosis.
AB  - OBJECTIVE: There is a need for second opinion histopathology referrals,
      especially for patients with head and neck pathology. The objective of this study
      was to determine the pattern and potential impact of referrals to a specialist
      oral and maxillofacial pathologist. STUDY DESIGN: Retrospective analysis of 566
      consecutive referrals with demographic and clinical information was performed.
      The original diagnosis and the specialists' second opinion diagnosis were
      compared to assess for discrepancies and potential effect on patient management.
      RESULTS: Seventy-five percent of cases were referred by general pathologists.
      Salivary gland (30%) and odontogenic tumors (12%) were the most commonly referred
      categories. Of the referred cases, 58 (9%) resulted in a significant change in
      diagnosis, impacting patient management. In 24 cases (4%) the diagnosis was
      revised from benign to malignant, and in 22 (4%) from malignant to benign.
      CONCLUSION: This study highlights the need for referrals to oral and
      maxillofacial pathologists. A second opinion may assist in accurate diagnosis and
      patient management.

PMID- 25956219
TI  - Use of an advanced 3-T MRI movie to investigate articulation.
AB  - OBJECTIVE: To develop a magnetic resonance imaging (MRI) movie to reveal the
      dynamic movement of articulators and teeth. STUDY DESIGN: Five healthy females
      with normal occlusion participated in this study. Various concentrations of MRI
      contrast media (ferric ammonium citrate [FAC]) were tested for visualization of
      teeth, according to facial markers and with the use of a gel. Custom-made
      circuitry was connected to synchronize pronunciation of fricative sounds (/asa/)
      with scans. Three gradient echo sequences (True fast imaging with steady state
      precession [true FISP], FISP, and fast low angle shot [FLASH]) with a segmented
      cine were tested with the use of repetition times (TRs) of 9 ms and 31.5 ms. The
      MRI movie images were superimposed over the boundaries of teeth. The images
      produced during pronunciation, using the two different TRs (9 ms and 31 ms), were
      compared to assess the position of the lips and the tongue. RESULTS: Images
      obtained using the FLASH sequence, with a TR of 9 ms or 31.5 ms, can be used for
      diagnostic purposes. A TR of 9 ms, with 161 continuous images acquired, produced
      the highest-quality images of teeth, with few artifacts present. Pronunciation of
      the consonant "s" was clearly discernable. CONCLUSIONS: Our 3-T MRI movie system,
      with a temporal resolution less than 9 ms, can provide detailed information
      pertaining to variations in speech or oropharyngeal function.

PMID- 25956220
TI  - Site-specific acetaldehyde production and microbial colonization in relation to
      oral squamous cell carcinoma and oral lichenoid disease.

PMID- 25956221
TI  - Statistical assessment of heavy metal pollution in sediments of east coast of
      Tamilnadu using Energy Dispersive X-ray Fluorescence Spectroscopy (EDXRF).
AB  - The study of heavy metal pollution in coastal sediments assumes importance with
      respect to environmental ecology in view of the rapid industrialization and
      increased anthropogenic activities. The concentrations of Mg, Al, K, Ca, Ti, Fe,
      V, Cr, Mn, Co, Ni and Zn were measured in twenty sampling sites along the east
      coast of Tamilnadu, India by energy dispersive X-ray fluorescence spectroscopy
      (EDXRF). Natural background values were used to delineate their origin as
      geogenic or anthropogenic. To interpret and assess the contamination status for
      heavy metals in sediments, four metal pollution indices used such as an
      enrichment factor, a geo-accumulation index, a contamination factor and a
      pollution load index. Multivariate statistical methods were applied to identify
      the source of heavy metals. Heavy metal toxicity risk was assessed using sediment
      quality guidelines. The presented methodology was used to determine the
      anthropogenic origin of heavy metals in the sediment. 

PMID- 25956224
TI  - A study on EEG-based brain electrical source of mild depressed subjects.
AB  - BACKGROUND AND OBJECTIVE: Several abnormal brain regions are known to be linked
      to depression, including amygdala, orbitofrontal cortex (OFC), anterior cingulate
      cortex (ACC), and dorsolateral prefrontal cortex (DLPFC) etc. The aim of this
      study is to apply EEG (electroencephalogram) data analysis to investigate, with
      respect to mild depression, whether there exists dysregulation in these brain
      regions. METHODS: EEG sources were assessed from 9 healthy and 9 mildly depressed
      subjects who were classified according to the Beck Depression Inventory (BDI)
      criteria. t-Test was used to calculate the eye movement data and standardized low
      resolution tomography (sLORETA) was used to correlate EEG activity. RESULTS: A
      comparison of eye movement data between the healthy and mild depressed subjects
      exhibited that mildly depressed subjects spent more time viewing negative
      emotional faces. Comparison of the EEG from the two groups indicated higher theta
      activity in BA6 (Brodmann area) and higher alpha activity in BA38. CONCLUSIONS:
      EEG source location results suggested that temporal pole activity to be
      dysregulated, and eye-movement data analysis exhibited mild depressed subjects
      paid much more attention to negative face expressions, which is also in
      accordance with the results of EEG source location.

PMID- 25956222
TI  - RNA polymerase molecular beacon as tool for studies of RNA polymerase-promoter
      interactions.
AB  - The molecular details of formation of transcription initiation complex upon the
      interaction of bacterial RNA polymerase (RNAP) with promoters are not completely
      understood. One way to address this problem is to understand how RNAP interacts
      with different parts of promoter DNA. A recently developed fluorometric RNAP
      molecular beacon assay allows one to monitor the RNAP interactions with various
      unlabeled DNA probes and quantitatively characterize partial RNAP-promoter
      interactions. This paper focuses on methodological aspects of application of this
      powerful assay to study the mechanism of transcription initiation complex
      formation by Escherichia coli RNA polymerase sigma(70) holoenzyme and its
      regulation by bacterial and phage encoded factors. 

PMID- 25956223
TI  - Hydrogen sulfide and hypoxia-induced changes in TASK (K2P3/9) activity and
      intracellular Ca(2+) concentration in rat carotid body glomus cells.
AB  - Acute hypoxia depolarizes carotid body chemoreceptor (glomus) cells and elevates
      intracellular Ca(2+) concentration ([Ca(2+)]i). Recent studies suggest that
      hydrogen sulfide (H2S) may serve as an oxygen sensor/signal in the carotid body
      during acute hypoxia. To further test such a role for H2S, we studied the effects
      of H2S on the activity of TASK channel and [Ca(2+)]i, which are considered
      important for mediating the glomus cell response to hypoxia. Like hypoxia, NaHS
      (a H2S donor) inhibited TASK activity and elevated [Ca(2+)]i. To inhibit the
      production of H2S, glomus cells were incubated (3h) with inhibitors of
      cystathionine-beta-synthase and cystathionine-gamma-lyase (DL-propargylglycine,
      aminooxyacetic acid, beta-cyano-L-alanine; 0.3 mM). SF7 fluorescence was used to
      assess the level of H2S production. The inhibitors blocked L-cysteine- and
      hypoxia-induced elevation of SF7 fluorescence intensity. In cells treated with
      the inhibitors, hypoxia produced an inhibition of TASK activity and a rise in
      [Ca(2+)]i, similar in magnitude to those observed in control cells. L-cysteine
      produced no effect on TASK activity or [Ca(2+)]i and did not affect hypoxia
      induced inhibition of TASK and elevation of [Ca(2+)]i. These findings suggest
      that under normal conditions, H2S is not a major signal in hypoxia-induced
      modulation of TASK channels and [Ca(2+)]i in isolated glomus cells.

PMID- 25956225
TI  - Analysis of urinary 8-isoprostane as an oxidative stress biomarker by stable
      isotope dilution using automated online in-tube solid-phase microextraction
      coupled with liquid chromatography-tandem mass spectrometry.
AB  - We have developed a simple and sensitive method for the determination of the
      oxidative stress biomarker 8-isoprostane (8-IP) in human urine by automated
      online in-tube solid-phase microextraction (SPME) coupled with liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) using a Zorbax Eclipse XDB-8
      column and 0.1% formic acid/methanol (25/75, v/v) as a mobile phase. Electrospray
      MS/MS for 8-IP was performed on an API 4000 triple quadruple mass spectrometer in
      negative ion mode. The optimum in-tube SPME conditions were 20 draw/eject cycles
      with a sample size of 40 MUL using a Carboxen 1006 PLOT capillary column for the
      extraction. The extracted compounds were easily desorbed from the capillary by
      passage of the mobile phase, and no carryover was observed. Total analysis time
      of this method including online extraction and analysis was about 30 min for each
      sample. The in-tube SPME LC-MS/MS method showed good linearity in the
      concentration range of 20-1000 pg/mL with a correlation coefficient r = 0.9999
      for 8-IP using a stable isotope-labeled internal standard, 8-IP-d4. The detection
      limit of 8-IP was 3.3 pg/mL and the proposed method showed 42-fold higher
      sensitivity than the direct injection method. The intra-day and inter-day
      precisions (relative standard deviations) were below 5.0% and 8.5% (n = 5),
      respectively. This method was applied successfully to the analysis of urine
      samples without pretreatment or interference peaks. The recovery rates of 8-IP
      spiked into urine samples were above 92%. This method is useful for assessing the
      effects of oxidative stress and antioxidant intake.

PMID- 25956226
TI  - Pharmacokinetic profile and metabolite identification of yuanhuapine, a bioactive
      component in Daphne genkwa by ultra-high performance liquid chromatography
      coupled with tandem mass spectrometry.
AB  - Daphne genkwa Sieb. et Zucc. (Thymelaeaceae) is mainly used for the treatment of
      edema, asthma, and cancer in China and Korea for centuries. The major bioactive
      components in D. genkwa are daphnane-type diterpenoids, which showed
      pharmacological activities such as antileukemic, antifertility and skin
      irritants. In this study, the pharmacokinetics and metabolism profile of
      yuanhuapine, an effective and toxic diterpenoid, was investigated in rats. The
      plasma exposure of yuanhuapine was determined by ultra-performance liquid
      chromatography tandem triple-quadrupole mass spectrometry (UPLC-TQ-MS), and the
      pharmacokinetic parameters were calculated using the DAS 2.0 pharmacokinetic
      program. The metabolites were identified through ultra-performance liquid
      chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS)
      and a MetabolynxTM (v4.1) program. After oral administration (5 mg/kg),
      yuanhuapine was slowly absorbed and reached a maximum concentration of 579.20 +/-
      212.85 ng/mL at 7.33 +/- 1.03 h, it also eliminated slowly. As the cumulative
      excretion of yuanhuapine in urine and feces were only 0.7% and 3.3%, we supposed
      that biotransformation in vivo was of significant importance to this component.
      Not only the prototype but also twelve metabolites were found and tentatively
      identified in rat urine after oral administration of yuanhuapine. The metabolic
      pathway mainly involves hydroxylation, methylation, glucuronidation and cysteine
      conjugation during the phase I and phase II biotransformation pathway. All the
      information gained here was useful in understanding the pharmacological actions
      and toxic properties of yuanhuapine, and providing a meaningful basis for
      clinical application of such a bioactive compound of herbal medicines.

PMID- 25956227
TI  - Determination of counterfeit medicines by Raman spectroscopy: Systematic study
      based on a large set of model tablets.
AB  - In the last decade, counterfeit pharmaceutical products have become a widespread
      issue for public health. Raman spectroscopy which is easy, non-destructive and
      information-rich is particularly suitable as screening method for fast
      characterization of chemicals and pharmaceuticals. Combined with chemometric
      techniques, it provides a powerful tool for the analysis and determination of
      counterfeit medicines. Here, for the first time, a systematic study of the
      benefits and limitations of Raman spectroscopy for the analysis of pharmaceutical
      samples on a large set of model tablets, varying with respect to chemical and
      physical properties, was performed. To discriminate between the different
      mixtures, a combination of dispersive Raman spectroscopy performing in
      backscattering mode and principal component analysis was used. The discrimination
      between samples with different coatings, a varying amount of active
      pharmaceutical ingredients and a diversity of excipients were possible. However,
      it was not possible to distinguish between variations of the press power, mixing
      quality and granulation. As a showcase, the change in Raman signals of commercial
      acetylsalicylic acid effervescent tablets due to five different storage
      conditions was monitored. It was possible to detect early small chemical changes
      caused by inappropriate storage conditions. These results demonstrate that Raman
      spectroscopy combined with multivariate data analysis provides a powerful
      methodology for the fast and easy characterization of genuine and counterfeit
      medicines. 

PMID- 25956228
TI  - Exogenous induction of HO-1 alleviates vincristine-induced neuropathic pain by
      reducing spinal glial activation in mice.
AB  - Chemotherapy drugs such as vincristine can produce painful peripheral neuropathy
      for which is still lack of effective treatment. Recent studies have demonstrated
      that neuroinflammation plays an important role in the pathogenesis of neuropathic
      pain. Heme oxygenase 1 (HO-1) was shown to mediate the resolution of
      inflammation. In this study, we investigated the contribution of HO-1 in the
      modulation of vincristine-induced pain and the mechanisms implicated. Injection
      of vincristine induced persistent mechanical allodynia and thermal hyperalgesia
      in mice. The expression of HO-1 mRNA and protein was increased in 2 weeks in the
      spinal cord. Immunostaining showed that HO-1 was mainly expressed in neurons of
      spinal cord dorsal horn in naive animals, but induced in astrocytes and microglia
      after vincristine injection. Intraperitoneal injection of HO-1 inducer increased
      HO-1 expression in the spinal cord and attenuated vincristine-induced pain.
      Persistent induction of HO-1 by intraspinal injection of HO-1-expressing
      lentivirus alleviated vincristine-induced pain for more than 2 weeks.
      Furthermore, vincristine induced activation of glial cells (astrocytes and
      microglia), phosphorylation of MAPKs (JNK, ERK, and p38), and production of TNF
      alpha and monocyte chemoattractant protein-1 in the spinal cord, which were all
      reduced by intrathecal injection of HO-1 inducer. Taken together, our data
      provide the first evidence that induction of HO-1 attenuates vincristine-induced
      neuropathic pain via inhibition of glia-mediated neuroinflammation in the spinal
      cord. This suggests that exogenously induced HO-1 may have potential as therapy
      in chemotherapy-induced neuropathic pain.

PMID- 25956230
TI  - Staged resection for vestibular schwannoma.
AB  - CONCLUSION: Surgery remains the preferred option for large vestibular schwannoma
      (VS). The presence of unpredictable intraoperative difficulties may convince the
      operator to suspend the surgery to avoid risks to patient life. Additional
      surgeries may be mandatory and are better performed using a transcochlear
      approach. High rates of complications, poor facial nerve results, and a
      percentage of incomplete removals should be expected in such unfavorable cases.
      OBJECTIVES: To review the results for nine cases of huge VS treated by staged
      resection. METHOD: A retrospective case review was performed for all nine
      patients who underwent staged resection of VS at the Gruppo Otologico between
      1984-2012. The decision to perform staged surgery was always made intra
      operatively after encountering unpredicted difficulties. RESULTS: The nine
      patients represented 0.3% of all patients who underwent VS surgery during the
      same period. Mean tumor size was 4.7 cm (range = 3.0-6.6 cm). Two cases required
      three surgeries, resulting in a total of 20 operations. In addition, two cases
      required pre-operative ventriculoperitoneal shunt and one required temporary
      tracheotomy. After the final stage of surgery, complete removal had been achieved
      in six of the nine patients. The facial nerve was never preserved anatomically.

PMID- 25956229
TI  - Expression of genes involved in the T cell signalling pathway in circulating
      immune cells of cattle 24 months following oral challenge with Bovine Amyloidotic
      Spongiform Encephalopathy (BASE).
AB  - BACKGROUND: Bovine Amyloidotic Spongiform Encephalopathy (BASE) is a variant of
      classical BSE that affects cows and can be transmitted to primates and mice. BASE
      is biochemically different from BSE and shares some molecular and histo
      pathological features with the MV2 sub-type of human sporadic Creutzfeld Jakob
      Disease (sCJD). RESULTS: The present work examined the effects of BASE on gene
      expression in circulating immune cells. Ontology analysis of genes differentially
      expressed between cattle orally challenged with brain homogenate from cattle
      following intracranial inoculation with BASE and control cattle identified three
      main pathways which were affected. Within the immune function pathway, the most
      affected genes were related to the T cell receptor-mediated T cell activation
      pathways. The differential expression of these genes in BASE challenged animals
      at 10,12 and 24 months following challenge, vs unchallenged controls, was
      investigated by real time PCR. CONCLUSIONS: The results of this study show that
      the effects of prion diseases are not limited to the CNS, but involve the immune
      system and particularly T cell signalling during the early stage following
      challenge, before the appearance of clinical signs.

PMID- 25956231
TI  - Mutation genotypes of RNF213 gene from moyamoya patients in Taiwan.
AB  - Moyamoya disease (MMD) is a disorder characterized by stenosis of bilateral
      internal carotid arteries with compensatory angiogenesis of the perforating blood
      vessels. Familial transmission in MMD is common. Recently, mutations in human
      RNF213 and ACTA2 genes were identified to be responsible for MMD. The present
      study was to determine whether Taiwanese MMD patients carried mutations in these
      two genes. Of the 36 MMD patients, eleven was found to have RNF213 mutations.
      Direct genetic sequencing identified four different RNF213 mutations in the 11
      patients from 8 families: five with a p.R4810K, one with p.A1622V, one with
      p.V3933M, and the other one with p.R4131C. The latter three represent novel
      missense mutations. No mutation in ACTA2 gene was identified. Clinically,
      cerebral infarction was common in patients with an RNF213 mutation (9/11). In
      addition, four mutant patients had developmental delay (4/11) and two had mental
      dysfunction (2/11). The magnetic resonance angiography of asymptomatic mutant
      carriers demonstrated high incidence of multiple stenosis of intracranial vessels
      (3/6, 50%). Since 30.6% (11/36) of Taiwanese moyamoya patients carry an RNF213
      mutation and intracranial arterial stenosis was found in half of the asymptomatic
      mutant carriers, it is suggested that the RNF213 mutation should form part of the
      diagnostic workup for MMD in clinical practice. 

PMID- 25956232
TI  - Link between cerebral blood flow and autonomic function in survivors of internal
      carotid artery occlusion.
AB  - PURPOSE: Symptomatic internal carotid artery occlusion (ICAO) is an important
      cause of cerebral ischemia with poor long-term outcome. Reductions in baroreflex
      function is reported in carotid atherosclerosis and implicated in increased risk
      of recurrent cardiovascular events. A distributed network of forebrain regions
      can exert modulatory influences over the cardio-vagal and baroreflex functions.
      The successful clinical translation of these approaches offers insights into
      underlying modulatory mechanisms and to possible therapeutic strategy. METHODS:
      This study enrolled 20 symptomatic ICAO survivors, 20 patients with small vessel
      disease (SVD) as risk control, and 20 healthy controls. All underwent a
      standardized evaluation of cardiovascular autonomic function testing that
      included baroreflex sensitivity (BRS), Valsalva ratio (VR), and heart rate
      response to deep breathing (HR_DB). The regional cerebral blood flow (rCBF) of
      the central autonomic network (CAN) was obtained from arterial spin-labeling
      magnetic resonance imaging. Parameters of autonomic function between symptomatic
      ICAO survivors with and those without recurrent cardiovascular events were
      compared. RESULTS: Valsalva ratio and HR_DB levels were significantly higher in
      the control group, followed by the SVD and ICAO groups (p=0.009 and p=0.007,
      respectively). Spontaneous BRS and BRS during the early phase II of Valsalva
      maneuver levels were both significantly higher in the control group, followed by
      the SVD and ICAO groups (p<0.001 and p=0.042, respectively). The rCBF of CAN
      inversely correlated with spontaneous BRS. CONCLUSION: Autonomic dysregulation,
      including reduced BRS and impaired cardio-vagal function in the convalescent
      stage ICAO, can persist for a long time. Reduced BRS is inversely correlated with
      CAN activity.

PMID- 25956233
TI  - Gait training in subacute non-ambulatory stroke patients using a full weight
      bearing gait-assistance robot: A prospective, randomized, open, blinded-endpoint
      trial.
AB  - BACKGROUND: This study was a prospective, randomized, open, blinded-endpoint
      trial with the aim of examining whether gait training with a gait-assistance
      robot (GAR) improves gait disturbances in subacute non-ambulatory hemiplegic
      stroke patients more than overground conventional gait training. The GAR adopts a
      robot arm control system with full weight bearing and foot pressure visual
      biofeedback. METHODS: Twenty-six hemiplegic patients were randomly assigned to
      either the GAR-assisted gait training (GAGT) group or the overground conventional
      gait training (OCGT) group. Both groups underwent 60 min of standard physical
      therapy and 20 min of GAGT or OCGT 5 days a week for 4 weeks. The primary outcome
      measure was the Functional Ambulation Classification (FAC). The secondary outcome
      measures were the peak torque of the extensor muscles in the lower extremities
      and a 10-m walking test. The lower extremity function was evaluated using the
      Fugl-Meyer Assessment, and activities of daily living were assessed using the
      Functional Independence Measure. RESULTS: The GAGT group demonstrated
      significantly greater improvements in FAC and peak torque on the unaffected side
      (p=0.02) than the OCGT group. Additionally, gait speed tended to be faster
      (p=0.07) in the GAGT group. CONCLUSIONS: GAGT combined with standard physical
      therapy in subacute non-ambulatory hemiplegic patients led to significant
      improvements in gait and peak torque on the unaffected side compared to OCGT.

PMID- 25956234
TI  - Exome analysis identified a novel missense mutation in the CLPP gene in a
      consanguineous Saudi family expanding the clinical spectrum of Perrault Syndrome
      type-3.
AB  - Perrault syndrome (PRLTS) is a clinically and genetically heterogeneous disorder.
      Both male and female patients suffer from sensory neuronal hearing loss in early
      childhood, and female patients are characterized by premature ovarian failure and
      infertility after puberty. Clinical diagnosis may not be possible in early life,
      because key features of PRLTS, for example infertility and premature ovarian
      failure, do not appear before puberty. Limb spasticity, muscle weakness, and
      intellectual disability have also been observed in PRLTS patients. Mutations in
      five genes, HSD17B4, HARS2, CLPP, LARS2, and C10orf2, have been reported in five
      subtypes of PRLTS. We discovered a consanguineous Saudi family with the PRLTS3
      phenotype showing an autosomal recessive mode of inheritance. The patients had
      developed profound hearing loss, brain atrophy, and lower limb spasticity in
      early childhood. For molecular diagnosis, we complimented genome-wide
      homozygosity mapping with whole exome sequencing analyses and identified a novel
      homozygous mutation in exon 6 of CLPP at chromosome 19p13.3. To our knowledge,
      early onset with regression is a unique feature of these PRLTS patients that has
      not been reported so far. This study broadens the clinical spectrum of PRLTS3. 

PMID- 25956235
TI  - Pharmacokinetic and pharmacodynamic evaluation of ramelteon : an insomnia
      therapy.
AB  - INTRODUCTION: Ramelteon , a selective melatonin receptor agonist, is the first
      member of a novel class of hypnotics. It is approved for the treatment of
      insomnia characterized by sleep onset difficulties in the US and Japan, but not
      in Europe. AREAS COVERED: The main clinical properties as well as safety issues
      of ramelteon are described. Relevant publications reporting ramelteon
      characteristics and its use in insomnia disorder were identified using PubMed and
      SciFinder databases up to January 2015. Additional information was collected from
      the US clinical trials database and from Takeda website. EXPERT OPINION: Despite
      its high prevalence and economic burden, insomnia disorder remains mostly
      untreated. Ramelteon has demonstrated sleep-promoting effects in clinical trials
      and clinical practice, and it is not associated with the adverse effects typical
      of other class of hypnotics. Its efficacy appears to be relatively modest
      compared to current insomnia therapeutics, and its use seems restricted to
      patients with sleep onset difficulties. Assessment of ramelteon effects on sleep
      quality and maintenance, daytime function and of improvements in comorbid
      insomnia conditions deserves further studies. The potential application of
      ramelteon in other pathological conditions could open the way to novel
      therapeutic approaches as well as to new market opportunities.

PMID- 25956236
TI  - F-BAR family proteins, emerging regulators for cell membrane dynamic changes-from
      structure to human diseases.
AB  - Eukaryotic cell membrane dynamics change in curvature during physiological and
      pathological processes. In the past ten years, a novel protein family, Fes/CIP4
      homology-Bin/Amphiphysin/Rvs (F-BAR) domain proteins, has been identified to be
      the most important coordinators in membrane curvature regulation. The F-BAR
      domain family is a member of the Bin/Amphiphysin/Rvs (BAR) domain superfamily
      that is associated with dynamic changes in cell membrane. However, the molecular
      basis in membrane structure regulation and the biological functions of F-BAR
      protein are unclear. The pathophysiological role of F-BAR protein is unknown.
      This review summarizes the current understanding of structure and function in the
      BAR domain superfamily, classifies F-BAR family proteins into nine subfamilies
      based on domain structure, and characterizes F-BAR protein structure, domain
      interaction, and functional relevance. In general, F-BAR protein binds to cell
      membrane via F-BAR domain association with membrane phospholipids and initiates
      membrane curvature and scission via Src homology-3 (SH3) domain interaction with
      its partner proteins. This process causes membrane dynamic changes and leads to
      seven important cellular biological functions, which include endocytosis,
      phagocytosis, filopodium, lamellipodium, cytokinesis, adhesion, and podosome
      formation, via distinct signaling pathways determined by specific domain-binding
      partners. These cellular functions play important roles in many physiological and
      pathophysiological processes. We further summarize F-BAR protein expression and
      mutation changes observed in various diseases and developmental disorders.
      Considering the structure feature and functional implication of F-BAR proteins,
      we anticipate that F-BAR proteins modulate physiological and pathophysiological
      processes via transferring extracellular materials, regulating cell trafficking
      and mobility, presenting antigens, mediating extracellular matrix degradation,
      and transmitting signaling for cell proliferation. 

PMID- 25956237
TI  - Approaches to studying and manipulating the enteric microbiome to improve autism
      symptoms.
AB  - There is a growing body of scientific evidence that the health of the microbiome
      (the trillions of microbes that inhabit the human host) plays an important role
      in maintaining the health of the host and that disruptions in the microbiome may
      play a role in certain disease processes. An increasing number of research
      studies have provided evidence that the composition of the gut (enteric)
      microbiome (GM) in at least a subset of individuals with autism spectrum disorder
      (ASD) deviates from what is usually observed in typically developing individuals.
      There are several lines of research that suggest that specific changes in the GM
      could be causative or highly associated with driving core and associated ASD
      symptoms, pathology, and comorbidities which include gastrointestinal symptoms,
      although it is also a possibility that these changes, in whole or in part, could
      be a consequence of underlying pathophysiological features associated with ASD.
      However, if the GM truly plays a causative role in ASD, then the manipulation of
      the GM could potentially be leveraged as a therapeutic approach to improve ASD
      symptoms and/or comorbidities, including gastrointestinal symptoms. One approach
      to investigating this possibility in greater detail includes a highly controlled
      clinical trial in which the GM is systematically manipulated to determine its
      significance in individuals with ASD. To outline the important issues that would
      be required to design such a study, a group of clinicians, research scientists,
      and parents of children with ASD participated in an interdisciplinary daylong
      workshop as an extension of the 1st International Symposium on the Microbiome in
      Health and Disease with a Special Focus on Autism (www.microbiome-autism.com).
      The group considered several aspects of designing clinical studies, including
      clinical trial design, treatments that could potentially be used in a clinical
      trial, appropriate ASD participants for the clinical trial, behavioral and
      cognitive assessments, important biomarkers, safety concerns, and ethical
      considerations. Overall, the group not only felt that this was a promising area
      of research for the ASD population and a promising avenue for potential treatment
      but also felt that further basic and translational research was needed to clarify
      the clinical utility of such treatments and to elucidate possible mechanisms
      responsible for a clinical response, so that new treatments and approaches may be
      discovered and/or fostered in the future. 

PMID- 25956239
TI  - Introduction.

PMID- 25956240
TI  - Concluding remarks.

PMID- 25956241
TI  - Sex differences in risk of hospitalization among emergency department patients
      with acute asthma.

PMID- 25956242
TI  - [Atypical intussusception caused by inflammatory myofibroblastic tumor].

PMID- 25956238
TI  - Gastrointestinal dysfunction in autism spectrum disorder: the role of the
      mitochondria and the enteric microbiome.
AB  - Autism spectrum disorder (ASD) affects a significant number of individuals
      worldwide with the prevalence continuing to grow. It is becoming clear that a
      large subgroup of individuals with ASD demonstrate abnormalities in mitochondrial
      function as well as gastrointestinal (GI) symptoms. Interestingly, GI
      disturbances are common in individuals with mitochondrial disorders and have been
      reported to be highly prevalent in individuals with co-occurring ASD and
      mitochondrial disease. The majority of individuals with ASD and mitochondrial
      disorders do not manifest a primary genetic mutation, raising the possibility
      that their mitochondrial disorder is acquired or, at least, results from a
      combination of genetic susceptibility interacting with a wide range of
      environmental triggers. Mitochondria are very sensitive to both endogenous and
      exogenous environmental stressors such as toxicants, iatrogenic medications,
      immune activation, and metabolic disturbances. Many of these same environmental
      stressors have been associated with ASD, suggesting that the mitochondria could
      be the biological link between environmental stressors and neurometabolic
      abnormalities associated with ASD. This paper reviews the possible links between
      GI abnormalities, mitochondria, and ASD. First, we review the link between GI
      symptoms and abnormalities in mitochondrial function. Second, we review the
      evidence supporting the notion that environmental stressors linked to ASD can
      also adversely affect both mitochondria and GI function. Third, we review the
      evidence that enteric bacteria that are overrepresented in children with ASD,
      particularly Clostridia spp., produce short-chain fatty acid metabolites that are
      potentially toxic to the mitochondria. We provide an example of this gut-brain
      connection by highlighting the propionic acid rodent model of ASD and the
      clinical evidence that supports this animal model. Lastly, we discuss the
      potential therapeutic approaches that could be helpful for GI symptoms in ASD and
      mitochondrial disorders. To this end, this review aims to help better understand
      the underlying pathophysiology associated with ASD that may be related to
      concurrent mitochondrial and GI dysfunction. 

PMID- 25956243
TI  - FBXL5 modulates HIF-1alpha transcriptional activity by degradation of CITED2.
AB  - CITED2 is a ubiquitously expressed nuclear protein exhibiting a high affinity for
      the cysteine-histidine-rich domain 1 (CH1) of the transcriptional co-activators
      CBP/p300. CITED2 is particularly efficient in the inhibition of the hypoxia
      inducible factor-1alpha (HIF-1alpha) dependent transcription by competing with it
      for the interaction with the CH1 domain. Here we report a direct and specific
      interaction between CITED2 and the F-box and leucine rich repeat protein 5
      (FBXL5), a substrate adaptor protein which is part of E3 ubiquitin ligase
      complexes mediating protein degradation by the proteasome. We demonstrated that
      depletion of FBXL5 by RNA interference led to an increase of CITED2 protein
      levels. Conversely, overexpression of FBXL5 caused the decrease of CITED2 protein
      levels in a proteasome-dependent manner, and impaired the interaction between
      CITED2 and the CH1 domain of p300 in living cells. In undifferentiated mouse
      embryonic stem cells, the overexpression of FBXL5 also reduced Cited2 protein
      levels. Finally, we evidenced that FBXL5 overexpression and the consequent
      degradation of CITED2 enabled the transcriptional activity of the N-terminal
      transactivation domain of HIF-1alpha. Collectively, our results highlighted a
      novel molecular interaction between CITED2 and FBXL5, which might regulate the
      steady state CITED2 protein levels and contribute to the modulation of gene
      expression by HIF-1alpha. 

PMID- 25956244
TI  - A novel multigene cloning method for the production of a motile ATPase.
AB  - With the advent of nanotechnology, new functional modules (e.g., nanomotors,
      nanoprobes) have become essential in several medical fields. Generally,
      mechanical modulators systems are the principal components of most cutting-edge
      technologies in modern biomedical applications. However, the in vivo use of
      motile probes has raised many concerns due to their low sensitivity and non
      biocompatibility. As an alternative, biological enzymatic engines have received
      increased attention. In particular, ATPases, which belong to a class of motile
      enzymes that catalyze chemical metabolic reactions, have emerged as a promising
      motor due to their improved biocompatibility and performance. However, ATPases
      usually suffer from lower functional activity and are difficult to express
      recombinantly in bacteria relative to their conventional and synthetic
      competitors. Here, we report a novel functional modified ATPase with both a
      simple purification protocol and enhanced motile activity. For this mutant
      ATPase, a new bacterial subcloning method was established. The ATPase-encoding
      sequence was redesigned so that the mutant ATPase could be easily produced in an
      Escherichia coli system. The modified thermophilic F1-ATPase (mTF1-ATPase)
      demonstrated 17.8unit/mg ATPase activity. We propose that derivatives of our
      ATPase may enable the development of novel in vitro and in vivo synthetic medical
      diagnostics, as well as therapeutics. 

PMID- 25956245
TI  - Quantification of cell lysis during CHO bioprocesses: Impact on cell count,
      growth kinetics and productivity.
AB  - High cell densities and high viability are critical quality attributes for
      mammalian bioprocesses. Determination of living and dead cell numbers is nowadays
      routinely performed by automated image-based cell analyzers or flow cytometry.
      However, complete lysis of cells is usually neglected by these devices. We
      present a novel method for robust quantification of lysed cell populations over
      the course of a CHO bioprocess. The release of lactate dehydrogenase (LDH) and
      double stranded genomic DNA in culture supernatants were used as markers for cell
      lysis. We considered the degradation of both markers over cultivation time, which
      significantly increased the amount of released LDH and DNA. For correct and
      robust estimation of lysed cell fractions, degradation of both markers over
      cultivation time was considered, where redundancy of markers allowed data
      reconciliation. Calculating the number of cells which were subject to complete
      cell lysis, we could show that this fraction makes up as much as 30% of the total
      produced biomass and is not described by measurements of image-based analyzers.
      Finally, we demonstrate that disregarding cell lysis heavily affects the
      calculation of biomass yields and growth rates and that increasing levels of cell
      lysis are related to decreased productivity. 

PMID- 25956247
TI  - Prediction accuracies for growth and wood attributes of interior spruce in space
      using genotyping-by-sequencing.
AB  - BACKGROUND: Genomic selection (GS) in forestry can substantially reduce the
      length of breeding cycle and increase gain per unit time through early selection
      and greater selection intensity, particularly for traits of low heritability and
      late expression. Affordable next-generation sequencing technologies made it
      possible to genotype large numbers of trees at a reasonable cost. RESULTS:
      Genotyping-by-sequencing was used to genotype 1,126 Interior spruce trees
      representing 25 open-pollinated families planted over three sites in British
      Columbia, Canada. Four imputation algorithms were compared (mean value (MI),
      singular value decomposition (SVD), expectation maximization (EM), and a newly
      derived, family-based k-nearest neighbor (kNN-Fam)). Trees were phenotyped for
      several yield and wood attributes. Single- and multi-site GS prediction models
      were developed using the Ridge Regression Best Linear Unbiased Predictor (RR
      BLUP) and the Generalized Ridge Regression (GRR) to test different assumption
      about trait architecture. Finally, using PCA, multi-trait GS prediction models
      were developed. The EM and kNN-Fam imputation methods were superior for 30 and
      60% missing data, respectively. The RR-BLUP GS prediction model produced better
      accuracies than the GRR indicating that the genetic architecture for these traits
      is complex. GS prediction accuracies for multi-site were high and better than
      those of single-sites while multi-site predictability produced the lowest
      accuracies reflecting type-b genetic correlations and deemed unreliable. The
      incorporation of genomic information in quantitative genetics analyses produced
      more realistic heritability estimates as half-sib pedigree tended to inflate the
      additive genetic variance and subsequently both heritability and gain estimates.
      Principle component scores as representatives of multi-trait GS prediction models
      produced surprising results where negatively correlated traits could be
      concurrently selected for using PCA2 and PCA3. CONCLUSIONS: The application of GS
      to open-pollinated family testing, the simplest form of tree improvement
      evaluation methods, was proven to be effective. Prediction accuracies obtained
      for all traits greatly support the integration of GS in tree breeding. While the
      within-site GS prediction accuracies were high, the results clearly indicate that
      single-site GS models ability to predict other sites are unreliable supporting
      the utilization of multi-site approach. Principle component scores provided an
      opportunity for the concurrent selection of traits with different phenotypic
      optima.

PMID- 25956248
TI  - A systematic review of multisensory cognitive-affective integration in
      schizophrenia.
AB  - The etymology of schizophrenia implies poor functional integration of sensory,
      cognitive and affective processes. Multisensory integration (MSI) is a
      spontaneous perceptual-cognitive process by which relevant information from
      multiple sensory modalities is extracted to generate a holistic experience.
      Deficits in MSI may hinder prompt and appropriate behavioural responses in a
      complex and transient environment. Despite extensive investigation of sensory,
      cognitive and affective processing in patients with schizophrenia, little is
      known about how MSI is affected in the illness. We systemically searched the
      PubMed electronic database and reviewed twenty-nine behavioural and neuroimaging
      studies examining MSI in patients with schizophrenia. The available evidence
      indicates impaired MSI for non-emotional stimuli in schizophrenia, especially for
      linguistic information. There is also evidence for altered MSI for emotional
      stimuli, although findings are inconsistent and may be modality-specific. Brain
      functional alterations in the superior temporal cortex and inferior frontal
      cortex appear to underlie the deficits in both non-emotional and emotional MSI.
      The limitations of the experimental paradigms used and directions for future
      research are also discussed. 

PMID- 25956249
TI  - The association between autism and schizophrenia spectrum disorders: A review of
      eight alternate models of co-occurrence.
AB  - Although now believed to be two distinct disorders, autism spectrum disorders
      (ASD) and schizophrenia spectrum disorders (SSD) share multiple phenotypic
      similarities and risk factors, and have been reported to co-occur at elevated
      rates. In this narrative review, we give a brief overview of the
      phenomenological, genetic, environmental, and imaging evidence for the overlap
      between ASD and SSD, highlighting similarities and areas of distinction. We
      examine eight possible alternate models of explanation for the association and
      comorbidity between the disorders, and set out a research agenda to test these
      models. Understanding how and why these disorders co-occur has important
      implications for diagnosis, treatment, and prognosis, as well as for developing
      fundamental aetiological models of the disorders. 

PMID- 25956250
TI  - Similar effects of intranasal oxytocin administration and acute alcohol
      consumption on socio-cognitions, emotions and behaviour: Implications for the
      mechanisms of action.
AB  - Oxytocin (OT) plays a critical role in the formation of long lasting social
      attachments across a range of mammalian species. Raising intracerebral OT levels
      by intranasal administration of the neuropeptide (inOT) can also have pronounced
      effects on human sociocognitive functioning. inOT has been associated with
      increasing altruism, generosity, empathy and trust while decreasing fear, anxiety
      and stress reactions via neural mechanisms which are yet to be fully elucidated.
      The observation of the prosocial effects of OT has led to speculation about the
      role the peptide might play in some psychiatric conditions and debate as to its
      potential therapeutic uses. Here we note the great similarity in the
      sociocognitive effects that can be induced by inOT and the effects of acute
      consumption of modest does of alcohol. We further reflect on how both compounds
      may act on limbic and prefrontal cortical structures to increase GABAergic
      transmission, thereby facilitating the release of prepotent responses, that is,
      more automatic responses which are associated with earlier developmental stages. 

PMID- 25956252
TI  - Oxytocin and the modulation of pain experience: Implications for chronic pain
      management.
AB  - In an acute environment pain has potential protective benefits. However when pain
      becomes chronic this protective effect is lost and the pain becomes an
      encumbrance. Previously unheralded substances are being investigated in an
      attempt to alleviate the burden of living with chronic pain. Oxytocin, a
      neuropeptide hormone, is one prospective pharmacotherapeutic agent gaining
      popularity. Oxytocin has the potential to modulate the pain experience due to its
      ubiquitous involvement in central and peripheral psychological and physiological
      processes, and thus offers promise as a therapeutic agent. In this review, we
      discuss previous effective applications of oxytocin in pain-free clinical
      populations and its potential use in the modulation of pain experience. We also
      address the slowly growing body of literature investigating the administration of
      oxytocin in clinical and experimentally induced pain in order to investigate the
      potential mechanisms of its reported analgesic actions. We conclude that oxytocin
      offers a potential novel avenue for modulating the experience of pain, and that
      further research into this area is required to map its therapeutic benefit. 

PMID- 25956253
TI  - The brain's code and its canonical computational motifs. From sensory cortex to
      the default mode network: A multi-scale model of brain function in health and
      disease.
AB  - A variety of anatomical and physiological evidence suggests that the brain
      performs computations using motifs that are repeated across species, brain areas,
      and modalities. The computational architecture of cortex, for example, is very
      similar from one area to another and the types, arrangements, and connections of
      cortical neurons are highly stereotyped. This supports the idea that each
      cortical area conducts calculations using similarly structured neuronal modules:
      what we term canonical computational motifs. In addition, the remarkable self
      similarity of the brain observables at the micro-, meso- and macro-scale further
      suggests that these motifs are repeated at increasing spatial and temporal scales
      supporting brain activity from primary motor and sensory processing to higher
      level behaviour and cognition. Here, we briefly review the biological bases of
      canonical brain circuits and the role of inhibitory interneurons in these
      computational elements. We then elucidate how canonical computational motifs can
      be repeated across spatial and temporal scales to build a multiplexing
      information system able to encode and transmit information of increasing
      complexity. We point to the similarities between the patterns of activation
      observed in primary sensory cortices by use of electrophysiology and those
      observed in large scale networks measured with fMRI. We then employ the canonical
      model of brain function to unify seemingly disparate evidence on the
      pathophysiology of schizophrenia in a single explanatory framework. We
      hypothesise that such a framework may also be extended to cover multiple brain
      disorders which are grounded in dysfunction of GABA interneurons and/or these
      computational motifs. 

PMID- 25956251
TI  - Sleep disruption and the sequelae associated with traumatic brain injury.
AB  - Sleep disruption, which includes a loss of sleep as well as poor quality
      fragmented sleep, frequently follows traumatic brain injury (TBI) impacting a
      large number of patients each year in the United States. Fragmented and/or
      disrupted sleep can worsen neuropsychiatric, behavioral, and physical symptoms of
      TBI. Additionally, sleep disruption impairs recovery and can lead to cognitive
      decline. The most common sleep disruption following TBI is insomnia, which is
      difficulty staying asleep. The consequences of disrupted sleep following injury
      range from deranged metabolomics and blood brain barrier compromise to altered
      neuroplasticity and degeneration. There are several theories for why sleep is
      necessary (e.g., glymphatic clearance and metabolic regulation) and these may
      help explain how sleep disruption contributes to degeneration within the brain.
      Experimental data indicate disrupted sleep allows hyperphosphorylated tau and
      amyloid beta plaques to accumulate. As sleep disruption may act as a cellular
      stressor, target areas warranting further scientific investigation include the
      increase in endoplasmic reticulum and oxidative stress following acute periods of
      sleep deprivation. Potential treatment options for restoring the normal sleep
      cycle include melatonin derivatives and cognitive behavioral therapy. 

PMID- 25956254
TI  - BDNF Val66Met polymorphism and hippocampal volume in neuropsychiatric disorders:
      A systematic review and meta-analysis.
AB  - BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved
      in neurogenesis and synaptic plasticity in the central nervous system, especially
      in the hippocampus, and has been implicated in the pathophysiology of several
      neuropsychiatric disorders. Its Val66Met polymorphism (refSNP Cluster Report:
      rs6265) is a functionally relevant single nucleotide polymorphism affecting the
      secretion of BDNF and is implicated in differences in hippocampal volumes.
      METHODS: This is a systematic meta-analytical review of findings from imaging
      genetic studies on the impact of the rs6265 SNP on hippocampal volumes in
      neuropsychiatric patients with major depressive disorder, anxiety, bipolar
      disorder or schizophrenia. RESULTS: The overall sample size of 18 independent
      clinical cohorts comprised 1695 patients. Our results indicated no significant
      association of left (Hedge's g=0.08, p=0.12), right (g=0.07, p=0.22) or bilateral
      (g=0.07, p=0.16) hippocampal volumes with BDNF rs6265 in neuropsychiatric
      patients. There was no evidence for a publication bias or any demographic,
      clinical, or methodological moderating effects. Both Val/Val homozygotes (g=0.32,
      p=0.004) and Met-carriers (g=0.20, p=0.004) from the patient sample had
      significantly smaller hippocampal volumes than the healthy control sample with
      the same allele. The magnitude of these effects did not differ between the two
      genotypes. CONCLUSION: This meta-analysis suggests that there is no association
      between this BDNF polymorphism and hippocampal volumes. For each BDNF genotype,
      the hippocampal volumes were significantly lower in neuropsychiatric patients
      than in healthy controls.

PMID- 25956255
TI  - Time windows matter in ADHD-related developing neuropsychological basic deficits:
      A comprehensive review and meta-regression analysis.
AB  - Normative development of neuropsychological functions that are assumed to
      underlie attention deficit/hyperactivity disorder (ADHD) may show transition
      periods, i.e., periods of heightened developmental discontinuity and reduced
      differential continuity. During such periods differences between ADHD cases and
      controls in these functions might be obscured because assessments probably not
      only reflect individual differences in the ADHD-related deviation but also
      individual differences in speed/onset of the transition. Our review focuses on
      executive inhibitory control (IC) and delay aversion/discounting (DA) because
      normative developmental processes of these characteristics are relatively well
      described. For complex IC performance a transition period can be assumed in
      preschool years, for DA around puberty. Published meta-analyses on
      neuropsychological IC tasks and a meta-regression analysis of 23 case-control
      comparisons in DA tasks comprising 1395 individuals with ADHD and 1195 controls
      confirmed our assumption. Effect sizes of case-control comparisons were
      significantly larger outside transition periods, i.e., in age-periods of relative
      developmental continuity. An increasingly precise identification of such time
      windows could contribute to the understanding of the etiological pathways of
      ADHD. 

PMID- 25956256
TI  - Hearing voices in the resting brain: A review of intrinsic functional
      connectivity research on auditory verbal hallucinations.
AB  - Resting state networks (RSNs) are thought to reflect the intrinsic functional
      connectivity of brain regions. Alterations to RSNs have been proposed to underpin
      various kinds of psychopathology, including the occurrence of auditory verbal
      hallucinations (AVH). This review outlines the main hypotheses linking AVH and
      the resting state, and assesses the evidence for alterations to intrinsic
      connectivity provided by studies of resting fMRI in AVH. The influence of
      hallucinations during data acquisition, medication confounds, and movement are
      also considered. Despite a large variety of analytic methods and designs being
      deployed, it is possible to conclude that resting connectivity in the left
      temporal lobe in general and left superior temporal gyrus in particular are
      disrupted in AVH. There is also preliminary evidence of atypical connectivity in
      the default mode network and its interaction with other RSNs. Recommendations for
      future research include the adoption of a common analysis protocol to allow for
      more overlapping datasets and replication of intrinsic functional connectivity
      alterations. 

PMID- 25956257
TI  - Comparative and cost effectiveness of telemedicine versus telephone counseling
      for smoking cessation.
AB  - BACKGROUND: In rural America, cigarette smoking is prevalent and health care
      providers lack the time and resources to help smokers quit. Telephone quitlines
      are important avenues for cessation services in rural areas, but they are poorly
      integrated with local health care resources. OBJECTIVE: The intent of the study
      was to assess the comparative effectiveness and cost effectiveness of two models
      for delivering expert tobacco treatment at a distance: telemedicine counseling
      that was integrated into smokers' primary care clinics (Integrated Telemedicine
      ITM) versus telephone counseling, similar to telephone quitline counseling,
      delivered to smokers in their homes (Phone). METHODS: Smokers (n=566) were
      recruited offline from 20 primary care and safety net clinics across Kansas. They
      were randomly assigned to receive 4 sessions of ITM or 4 sessions of Phone
      counseling. Patients in ITM received real-time video counseling, similar to
      Skype, delivered by computer/webcams in clinic exam rooms. Three full-time
      equivalent trained counselors delivered the counseling. The counseling duration
      and content was the same in both groups and was available in Spanish or English.
      Both groups also received identical materials and assistance in selecting and
      obtaining cessation medications. The primary outcome was verified 7-day point
      prevalence smoking abstinence at month 12, using an intent-to-treat analysis.
      RESULTS: There were no significant baseline differences between groups, and the
      trial achieved 88% follow-up at 12 months. Verified abstinence at 12 months did
      not significantly differ between ITM or Phone (9.8%, 27/280 vs 12%, 34/286;
      P=.406). Phone participants completed somewhat more counseling sessions than ITM
      (mean 2.6, SD 1.5 vs mean 2.4, SD 1.5; P=.0837); however, participants in ITM
      were significantly more likely to use cessation medications than participants in
      Phone (55.9%, 128/280 vs 46.1%, 107/286; P=.03). Compared to Phone participants,
      ITM participants were significantly more likely to recommend the program to a
      family member or friend (P=.0075). From the combined provider plus participant
      (societal) perspective, Phone was significantly less costly than ITM.
      Participants in ITM had to incur time and mileage costs to travel to clinics for
      ITM sessions. From the provider perspective, counseling costs were similar
      between ITM (US $45.46, SD 31.50) and Phone (US $49.58, SD 33.35); however, total
      provider costs varied widely depending on how the clinic space for delivering ITM
      was valued. CONCLUSIONS: Findings did not support the superiority of ITM over
      telephone counseling for helping rural patients quit smoking. ITM increased
      utilization of cessation pharmacotherapy and produced higher participant
      satisfaction, but Phone counseling was significantly less expensive. Future
      interventions could combine elements of both approaches to optimize
      pharmacotherapy utilization, counseling adherence, and satisfaction. Such an
      approach could commence with a telemedicine-delivered clinic office visit for
      pharmacotherapy guidance, and continue with telephone or real-time video
      counseling delivered via mobile phones to flexibly deliver behavioral support to
      patients where they most need it-in their homes and communities. TRIAL
      REGISTRATION: Clinicaltrials.gov NCT00843505;
      http://clinicaltrials.gov/ct2/show/NCT00843505 (Archived by WebCite at
      http://www.webcitation.org/6YKSinVZ9).

PMID- 25956258
TI  - MTHFR deficiency or reduced intake of folate or choline in pregnant mice results
      in impaired short-term memory and increased apoptosis in the hippocampus of wild
      type offspring.
AB  - Genetic or nutritional disturbances in one-carbon metabolism, with associated
      hyperhomocysteinemia, can result in complex disorders including pregnancy
      complications and neuropsychiatric diseases. In earlier work, we showed that mice
      with a complete deficiency of methylenetetrahydrofolate reductase (MTHFR), a
      critical enzyme in folate and homocysteine metabolism, had cognitive impairment
      with disturbances in choline metabolism. Maternal demands for folate and choline
      are increased during pregnancy and deficiencies of these nutrients result in
      several negative outcomes including increased resorption and delayed development.
      The goal of this study was to investigate the behavioral and neurobiological
      impact of a maternal genetic deficiency in MTHFR or maternal nutritional
      deficiency of folate or choline during pregnancy on 3-week-old Mthfr(+/+)
      offspring. Mthfr(+/+) and Mthfr(+/-) females were placed on control diets (CD);
      and Mthfr(+/+) females were placed on folate-deficient diets (FD) or choline
      deficient diets (ChDD) throughout pregnancy and lactation until their offspring
      were 3weeks of age. Short-term memory was assessed in offspring, and hippocampal
      tissue was evaluated for morphological changes, apoptosis, proliferation and
      choline metabolism. Maternal MTHFR deficiency resulted in short-term memory
      impairment in offspring. These dams had elevated levels of plasma homocysteine
      when compared with wild-type dams. There were no differences in plasma
      homocysteine in offspring. Increased apoptosis and proliferation was observed in
      the hippocampus of offspring from Mthfr(+/-) mothers. In the maternal FD and ChDD
      study, offspring also showed short-term memory impairment with increased
      apoptosis in the hippocampus; increased neurogenesis was observed in ChDD
      offspring. Choline acetyltransferase protein was increased in the offspring
      hippocampus of both dietary groups and betaine was decreased in the hippocampus
      of FD offspring. Our results reveal short-term memory deficits in the offspring
      of dams with MTHFR deficiency or dietary deficiencies of critical methyl donors.
      We suggest that deficiencies in maternal one-carbon metabolism during pregnancy
      can contribute to hippocampal dysfunction in offspring through apoptosis or
      altered choline metabolism.

PMID- 25956260
TI  - Modernisation, smoking and chronic disease: Of temporality and spatiality in
      global health.
AB  - This article explores the spatio-temporal logics at work in global health.
      Influenced by ideas of time-space compression, the global health literature
      argues that the world is characterised by a convergence of disease patterns and
      biomedical knowledge. While not denying the influence of these temporalities and
      spatialities of globalisation within the global health and chronic disease field,
      the article argues that they sit alongside other, often-conflicting notions of
      time and space. To do so, it explores the spatio-temporal logics that underpin a
      highly influential epidemiological model of the smoking epidemic. Unlike the
      temporalities and spatialities of sameness described in much of the global health
      literature, the article shows that this model is articulated around temporalities
      and spatialities of difference. This is not the difference celebrated by
      postmoderns, but the difference of modernisation theorists built around nations,
      sequential stages and progress. Indeed, the model, in stark contrast to the 'one
      world, one time, one health' globalisation mantra, divides the world into nation
      states and orders them along epidemiological, geographical and development lines.

PMID- 25956259
TI  - Human adipose-derived stem cells partially rescue the stroke syndromes by
      promoting spatial learning and memory in mouse middle cerebral artery occlusion
      model.
AB  - INTRODUCTION: Growing evidence has brought stem cell therapy to the forefront as
      new promising approaches towards stroke treatment. Of all candidate seeding
      cells, adipose-derived stem cells (ADSCs) are considered as one of the most
      appropriate for stroke treatment. However, previous experimental data could not
      reach to an agreement on the efficacy of ADSC transplantation for treating stroke
      in vivo as well as its mechanism which hinders their further clinical
      translational application. METHODS: To explore their in vivo mechanism of hADSC
      administration on neurological injury, hADSC were labeled with Enhanced Green
      Fluorescence Protein expressing FG12 lentivirus and injected into MCAO mouse
      infarct area by in situ way. Neurological function was evaluated by Rogers
      Scaling System and their spatial learning and memory was determined by Morris
      Test. 2,3,5-triphenyltetrazolium chloride was carried out to compare the infarct
      area among groups. Histoimmunostaining was used to track the injected hADSCs for
      their in vivo migration, transdifferentiation and integration with the endogenous
      neuronal circuitry. To better address the underlying rescuing mechanism, qRT-PCR
      was performed on neural markers of MBP, MAP2, GFAP, microglia marker of Iba1.
      RESULTS: It was found that hADSCs could promote both spatial learning and memory
      of MCAO mice. Co-localization of GFP and MAP2 were found in the whole cortex with
      significantly (P<0.01) higher percentage at the contralateral cortex compared
      with the ipsilateral cortex. Low percentage of GFP and GFAP co-localized cells
      were found at whole cortex. Meanwhile, Iba1(+) microglia and GFAP(+) astrocyte
      cells were significantly (P<0.05) suppressed by hADSC injection. CONCLUSIONS:
      hADSCs could transdifferentiate into neuron like cells (MAP2(+)) in vivo and
      probably used as seeding cells for replacement based stem cell therapy of stroke.
      Also, significant immunomodulation was found. Meanwhile hADSCs could
      significantly protect the endogenous neuron survival. This study demonstrated
      that hADSC intervention with MCAO mice could apparently ameliorate stroke
      symptoms by direct cell replacement, enhanced immnunosuppression and increasing
      the viability of endogenous neurons.

PMID- 25956261
TI  - Effect of different rehydration temperatures on the survival of human vitrified
      warmed oocytes.
AB  - PURPOSE: To evaluate the effect of different exposure temperatures during the
      dilution process on the survival rate of vitrified oocytes and following
      development. METHODS: Patients were divided at random into two groups for
      different dilution temperature (20-22  degrees C, RT group; 37  degrees C,37 
      degrees C group) according to computer-generated random numbers on the day of
      oocyte warming. The survival and fertilization rates of vitrified oocytes as well
      as the implantation and clinical pregnancy rates of the resulting embryos were
      recorded. RESULTS: A total of 662 and 676 oocytes were warmed in the 37  degrees
      C group and RT group, respectively, and significant difference was observed in
      the survival rate between 37  degrees C group (88.37%) and RT group (79.88%) (P =
      0.0000). There was significant difference between the survival rate of 37 
      degrees C group (87.27%) and RT group (75.64%) in nondonor patients (P = 0.0001).
      Multiple linear regression analysis showed that dilution temperature (beta =
      0.079, P = 0.017) and clinical outcomes of fresh cycles (beta = 0.063, P = 0.001)
      were significantly and independently associated with survival rate. No
      significant difference was found between the 37  degrees C group and RT group in:
      fertilization rate (66.67 versus 65.37%), implantation rate (20.0 versus 19.46%),
      clinical pregnancy rate (37.5 versus 35.0%). CONCLUSIONS: In conclusion, the
      results of this study give supportive evidence of the application of 37  degrees
      C in the dilution process, especially for oocytes of poor quality. Further
      studies with well-controlled experimental groups are needed to optimize protocols
      for human oocyte vitrification.

PMID- 25956262
TI  - Healthy twin live-birth after ionophore treatment in a case of theophylline
      resistant Kartagener syndrome.
AB  - PURPOSE: To evaluate whether it is a feasible option to target the oocyte (with
      Ca(2+)-ionophore) in case that sperm motility cannot be restored in Kartagener
      syndrome. METHODS: A case of a male Kartagener syndrome with exclusively immotile
      spermatozoa that did not react to the dimethylxanthine theophylline. Thus, half
      of the associated oocytes were treated for 15 min with the ready-to-use-
      ionophore CultActive immediately after ICSI whereas the other 50 % were injected
      with routine ICSI without artificial oocyte activation. Rates of fertilization,
      blastulation, pregnancy and live birth were evaluated. RESULTS: Fertilization
      check revealed that none of the conventionally injected but 4/6 (66.7 %) of the
      artificially activated oocytes showed two pronuclei. Three embryos were of good
      and one of fair quality. Corresponding blastocyst formation rate was 3 out of 4
      (75 %). A double embryo transfer led to a healthy twin birth in the 34th week of
      gestation (two boys with a birth weight of 1724 g and 2199 g). CONCLUSIONS: This
      case indicates that Ca(2+)-ionophore treatment in cycles from theophylline
      resistant Kartagener syndrome patients is a feasible option. The future will show
      if routine application of A23187 in Kartagener or primary cilia dyskinesis
      patients will be of benefit.

PMID- 25956263
TI  - Assessment of aneuploidy formation in human blastocysts resulting from donated
      eggs and the necessity of the embryos for aneuploidy screening.
AB  - PURPOSE: To examine the prevalence of aneuploidy in human blastocysts resulting
      from donated eggs and embryo implantation after transfer of normal euploid
      embryos. Also, to assess the necessity of preimplantation genetic screening (PGS)
      for embryos produced with donor eggs. METHODS: Blastocysts from donor-recipient
      cycles were biopsied for PGS (PGS group) and the samples were analyzed with DNA
      microarray. Euploid blastocysts were transferred to the recipients, and both
      clinical pregnancy and embryo implantation were examined and compared with
      embryos without PGS (control group). RESULTS: After PGS, 39.1 % of blastocysts
      were abnormal, including aneuploidy and euploid with partial chromosome deletion
      and/or duplication. Transfer of normal euploid blastocysts brought about 72.4 %
      of clinical pregnancy, 65.5 % of ongoing/delivery and 54.9 % of embryo
      implantation rates; these rates were slightly higher than those in the control
      group (66.7, 54.0 and 47.8 %, respectively), but there was no statistical
      difference between the two groups. By contrast, the miscarriage rate was higher
      in the control group (19.2 %) than in the PGS group (9.5 %), but no statistical
      difference was observed. Transfer of two or more embryos did not significantly
      increase the ongoing/delivery rates in both groups, but significantly increased
      the twin pregnancy rates (50.0 % in the PGS group and 43.8 % in the control
      group). CONCLUSION(S): High proportions of human blastocysts derived from donor
      eggs are aneuploid. Although pregnancy and embryo implantation rates were
      increased, and miscarriage rates were reduced by transfer of embryos selected by
      PGS, the efficiency was not significantly different as compared to the control,
      suggesting that PGS may be necessary only in some specific situations, such as
      single embryo transfer.

PMID- 25956265
TI  - When three is a crowd: on keeping outsiders out!

PMID- 25956264
TI  - High mobility group box 1 protein polymorphism affects susceptibility to
      recurrent pregnancy loss by up-regulating gene expression in chorionic villi.
AB  - PURPOSE: Inflammation in chorionic villi is involved in the development of
      recurrent pregnancy loss (RPL). High mobility group box 1 protein (HMGB1) plays
      critical roles in inflammation and expression of the protein can be found in
      chorionic villi. The purpose of the study was to investigate the association
      between HMGB1 genetic polymorphisms and susceptibility to RPL and to examine the
      mechanism underlying this correlation. METHODS: Two HMGB1 polymorphisms,
      rs2249825C/G and rs1412125T/C, were examined in 112 RPL patients and 118 healthy
      controls by the polymerase chain reaction-restriction fragment length
      polymorphism assay. RESULTS: Percentage of rs2249825GG was significantly
      increased in patients than in controls (Odd ratio [OR] =2.33, 95 % confidence
      interval [CI]: 1.18-4.58, P = 0.013). Also, prevalence of rs2249825G allele was
      significantly higher in RPL cases (OR = 1.77, 95 % CI: 1.20-2.62, P = 0.004).
      Function analysis of rs2249825C/G revealed that the polymorphism did not affect
      serum level of HMGB1. Interestingly, we found significantly increased level of
      HMGB1 in chorionic villi from RPL patients. Moreover, patients with rs2249825GG
      genotype presented significantly elevated level of HMGB1 in chorionic villi
      compared to those with CG or CC genotypes. CONCLUSIONS: These results suggest
      that HMGB1 rs2249825C/G polymorphism is associated with increased risk of RPL and
      can elevate gene expression in chorionic villi.

PMID- 25956266
TI  - The potential role of advanced glycation end products (AGEs) and soluble
      receptors for AGEs (sRAGE) in the pathogenesis of adult-onset still's disease.
AB  - BACKGROUND: Accumulating evidence has demonstrated a pathogenic role of advanced
      glycation end products (AGEs) and receptors for AGEs (RAGE) in inflammation.
      Soluble RAGE (sRAGE), with the same ligands-binding capacity as full-length RAGE,
      acts as a "decoy" receptor. However, there has been scanty data regarding AGEs
      and sRAGE in adult-onset Still's disease (AOSD). This study aimed to investigate
      AGEs and sRAGE levels in AOSD patients and examine their association with
      clinical characteristics. METHODS: Using ELISA, plasma levels of AGEs and sRAGE
      were determined in 52 AOSD patients, 36 systemic lupus erythematosus(SLE)
      patients and 16 healthy controls(HC). Their associations with activity parameters
      and disease courses were evaluated. RESULTS: Significantly higher median levels
      of AGEs were observed in active AOSD patients (16.75 pg/ml) and active SLE
      patients (14.80 pg/ml) than those in HC (9.80 pg/ml, both p < 0.001). AGEs levels
      were positively correlated with activity scores (r = 0.836, p < 0.001), ferritin
      levels (r = 0.372, p < 0.05) and CRP levels (r = 0.396, p < 0.005) in AOSD
      patients. Conversely, significantly lower median levels of sRAGE were observed in
      active AOSD patients (632.2 pg/ml) and active SLE patients (771.6 pg/ml) compared
      with HC (1051.7 pg/ml, both p < 0.001). Plasma sRAGE levels were negatively
      correlated with AOSD activity scores (r = -0.320, p < 0.05). In comparison to
      AOSD patients with monocyclic pattern, significantly higher AGEs levels were
      observed in those with polycyclic or chronic articular pattern. With treatment,
      AGEs levels declined while sRAGE levels increased in parallel with the decrease
      in disease activity. CONCLUSION: The elevation of AGEs levels with concomitant
      decreased sRAGE levels in active AOSD patients, suggests their pathogenic role in
      AOSD.

PMID- 25956267
TI  - Evaluation of dental implants as a risk factor for the development of
      bisphosphonate-related osteonecrosis of the jaw in breast cancer patients.
AB  - It remains unclear whether dental implants are a risk factor for the development
      of bisphosphonate-related osteonecrosis of the jaw (BRONJ). We retrospectively
      evaluated the status of dental implants in patients given intravenous
      bisphosphonates (BPs) in a breast cancer cohort to elucidate the risk for BRONJ
      at the implant site. We established a BRONJ oral monitoring program for 247
      breast cancer patients given intravenous BP in our institution. The 3-year
      cumulative incidence rate was determined. The systemic and local risk factors of
      44 patients who completed comprehensive oral examinations were evaluated by
      logistic regression analysis. The 3-year cumulative incidence rate of the 247
      patients was 0.074 % (8/247, 95 % CI 0.0081-0.014). In the 44 orally examined
      patients, 6 (13.6 %: 6/44) had dental implants. Of these 6 patients, 1 developed
      BRONJ at the implant site. There were no significant differences in the age,
      total BP treatment period, number of residual teeth, time of regular oral
      monitoring, oral hygiene level, or dental implant insertion. Although a case of
      ONJ was identified, dental implants which were inserted before intravenous BP
      administration were not a risk factor for the development of ONJ in breast cancer
      patients. 

PMID- 25956268
TI  - Parental smoking, maternal alcohol, coffee and tea consumption during pregnancy,
      and childhood acute leukemia: the ESTELLE study.
AB  - PURPOSE: To investigate the role of parental smoking during pre-conception and
      pregnancy, maternal beverage consumption (alcohol, coffee and tea) during
      pregnancy and their possible interactions, in the etiology of childhood acute
      leukemia (CL). METHODS: The ESTELLE study included 747 cases of CL [636 cases of
      acute lymphoblastic leukemia (ALL) and 100 cases of acute myeloblastic leukemia
      (AML)] diagnosed in France in 2010-2011 and 1,421 population controls frequency
      matched with the cases on age and gender. Data were obtained from structured
      telephone questionnaires administered to the mothers. The odds ratios (OR) and
      their 95 % confidence intervals were estimated using unconditional logistic
      regression models adjusted for potential confounders. RESULTS: AML, but not ALL,
      was non-significantly associated with alcohol drinking during pregnancy [OR = 1.3
      (0.8-2.0)] with a significant positive dose-response trend (p-trend = 0.02). Pre
      conception paternal smoking was significantly associated with ALL [OR = 1.2 (1.1
      1.5)] and AML [OR = 1.5 (1.0-2.3)]. CL was not associated with maternal smoking
      [OR = 1.0 (0.8-1.2)], or maternal coffee [OR = 0.9 (0.8-1.1)] or tea drinking [OR
      = 0.9 (0.8-1.1)] during pregnancy. However, a high consumption of coffee (>2
      cups/day) was significantly associated with ALL [OR = 1.3 (1.0-1.8)].
      CONCLUSIONS: The findings constitute additional evidence that maternal alcohol
      drinking during pregnancy may be involved in AML, and that paternal smoking
      before pregnancy may be a risk factor for CL. The role of maternal coffee
      drinking in CL remains unclear and should be investigated further in consortium
      analyses and in large birth cohort studies with exposure assessment more
      contemporaneous with the exposure, before the occurrence of the disease.

PMID- 25956269
TI  - Survival among Black and White patients with renal cell carcinoma in an equal
      access health care system.
AB  - PURPOSE: Unequal access to health care may be a reason for shorter survival among
      Black patients with renal cell carcinoma (RCC) than among their White
      counterparts. No studies have investigated survival disparity among RCC patients
      in an equal-access health care delivery system. This study aimed to examine
      racial differences in survival among clear cell RCC patients in the Department of
      Defense's (DoD) Military Health System (MHS), which provides equal access to care
      to all persons. METHODS: The study used the DoD's Automated Central Tumor
      Registry to identify 2056 White patients and 370 Black patients diagnosed with
      clear cell RCC between 1988 and 2004. The subjects were followed through 2007
      with a median follow-up time of 4.8 years. Kaplan-Meier survival curves were
      compared and a Cox model was used to estimate the hazard ratios (HRs) associated
      with survival by race. RESULTS: During follow-up, 1,027 White and 158 Black
      patients died. The Kaplan-Meier curves showed that Black patients had more
      favorable overall survival than did White patients (log rank p = 0.031). After
      adjustment for demographic, tumor, and treatment variables, the Cox model showed
      no statistically significant racial difference overall (adjusted HR 1.07, 95 % CI
      0.90-1.28) or stratified by age, sex or tumor stage. However, among patients who
      did not undergo surgery, Black patients had poorer survival than White patients.
      CONCLUSIONS: The lack of racial difference in survival among RCC patients in the
      MHS may be related to equal access to health care. Improved access could reduce
      the survival disparity among RCC patients in the general population.

PMID- 25956271
TI  - Associations between diabetes medication use and risk of second breast cancer
      events and mortality.
AB  - PURPOSE: Diabetes and certain diabetes medications have been shown to influence
      breast cancer (BC) risk. Less is known about their relation to BC outcomes. Our
      objective was to evaluate the effects of diabetes and diabetes medications on
      risk of second breast cancer events (SBCE) and mortality. METHODS: This
      population-based cohort study was conducted among women diagnosed with early
      stage (I-II) BC and enrolled in an integrated health plan. Exposures of interest
      were diabetes and medication classes including insulin, metformin, and
      sulfonylureas. Outcomes of interest were SBCE defined as recurrence or second
      primary BC, BC-specific mortality, and all-cause mortality. We used multivariable
      Cox proportional hazards models to estimate hazard ratios (HR) and 95 %
      confidence intervals (CI) for diabetes and medication use while accounting for
      potential confounders and competing risks. RESULTS: Among 4,216 women, 13 %
      developed SBCE during a median follow-up of 6.3 years. 610 women had diabetes of
      which 76 % used oral diabetes medication and/or insulin. Findings suggested that
      diabetes increased the risk of recurrence (HR = 1.57; 95 % CI 1.09-2.25) but not
      overall SBCE (HR = 1.29; 95 % CI 0.94-1.76) or second primary BC (HR = 0.74; 95 %
      CI 0.39-1.41). Among women with diabetes, insulin use was associated with
      increased risks of recurrence (HR = 1.94; 95 % CI 1.08-3.48) and all-cause
      mortality (HR = 2.33; 95 % CI 1.70-3.20). Metformin use was associated with lower
      all-cause mortality (HR = 0.55; 95 % CI 0.38-0.79). CONCLUSIONS: Our findings
      show an association between diabetes and increased recurrence risk, and risk may
      be greater among insulin users. Metformin may reduce all-cause mortality among BC
      survivors. Given the growing breast cancer survivor population, further research
      in larger, more diverse populations is warranted.

PMID- 25956270
TI  - Proceedings of the second international molecular pathological epidemiology (MPE)
      meeting.
AB  - Disease classification system increasingly incorporates information on pathogenic
      mechanisms to predict clinical outcomes and response to therapy and intervention.
      Technological advancements to interrogate omics (genomics, epigenomics,
      transcriptomics, proteomics, metabolomics, metagenomics, interactomics, etc.)
      provide widely open opportunities in population-based research. Molecular
      pathological epidemiology (MPE) represents integrative science of molecular
      pathology and epidemiology. This unified paradigm requires multidisciplinary
      collaboration between pathology, epidemiology, biostatistics, bioinformatics, and
      computational biology. Integration of these fields enables better understanding
      of etiologic heterogeneity, disease continuum, causal inference, and the impact
      of environment, diet, lifestyle, host factors (including genetics and immunity),
      and their interactions on disease evolution. Hence, the Second International MPE
      Meeting was held in Boston in December 2014, with aims to: (1) develop conceptual
      and practical frameworks; (2) cultivate and expand opportunities; (3) address
      challenges; and (4) initiate the effort of specifying guidelines for MPE. The
      meeting mainly consisted of presentations of method developments and recent data
      in various malignant neoplasms and tumors (breast, prostate, ovarian and
      colorectal cancers, renal cell carcinoma, lymphoma, and leukemia), followed by
      open discussion sessions on challenges and future plans. In particular, we
      recognized need for efforts to further develop statistical methodologies. This
      meeting provided an unprecedented opportunity for interdisciplinary
      collaboration, consistent with the purposes of the Big Data to Knowledge, Genetic
      Associations and Mechanisms in Oncology, and Precision Medicine Initiative of the
      US National Institute of Health. The MPE meeting series can help advance
      transdisciplinary population science and optimize training and education systems
      for twenty-first century medicine and public health. 

PMID- 25956272
TI  - Silicone impression material foreign body in the middle ear: Two case reports and
      literature review.
AB  - We report two cases of impression material foreign body in the middle ear. The
      first case had been affected with chronic otitis media. The silicone flowed into
      the middle ear through a tympanic membrane perforation during the process of
      making an ear mold. About 4 years and 8 months after, the patient had severe
      vertigo and deafness. We found bone erosion of the prominence of the lateral
      semicircular canal and diagnosed labyrinthitis caused by silicone impression
      material. In the second case silicone flowed into the canal wall down mastoid
      cavity. Both cases required surgery to remove the foreign body. The clinical
      courses in such cases are variable and timing of surgery is sometimes difficult.
      In addition to reporting these two cases, we present here a review of the
      literature regarding impression material foreign bodies. 

PMID- 25956273
TI  - Who is at higher risk of hypertension? Socioeconomic status differences in blood
      pressure among Polish adolescents: a population-based ADOPOLNOR study.
AB  - In Poland, there is no data on parental socioeconomic status (SES) as a potent
      risk factor in adolescent elevated blood pressure, although social differences in
      somatic growth and maturation of children and adolescents have been recorded
      since the 1980s. This study aimed to evaluate the association between parental
      SES and blood pressure levels of their adolescent offspring. A cross-sectional
      survey was carried out between 2009 and 2010 on a sample of 4941 students (2451
      boys and 2490 girls) aged 10-18, participants in the ADOPOLNOR study. The
      depended outcome variable was the level of blood pressure (optimal, pre- and
      hypertension) and explanatory variables included place of residence and
      indicators of parental SES: family size, parental educational attainments and
      occupation status, income adequacy and family wealth. The final selected model of
      the multiple multinomial logistic regression analysis (MLRA) with backward
      elimination procedure revealed the multifactorial dependency of blood pressure
      levels on maternal educational attainment, paternal occupation and income
      adequacy interrelated to urbanization category of the place of residence after
      controlling for family history of hypertension, an adolescent's sex, age and
      weight status. Consistent rural-to-urban and socioeconomic gradients were found
      in prevalence of elevated blood pressure, which increased with continuous lines
      from large cities through small- to medium-sized cities to villages and from high
      SES to low-SES familial environments. The adjusted likelihood of developing
      systolic and diastolic hypertension decreased with each step increase in maternal
      educational attainment and increased urbanization category. The likelihood of
      developing prehypertension decreased with increased urbanization category,
      maternal education, paternal employment status and income adequacy. Weight status
      appeared to be the strongest confounder of adolescent blood pressure level and,
      at the same time, a mediator between their blood pressure and parental SES.
      CONCLUSION: The findings of the present study confirmed socioeconomic disparities
      in blood pressure levels among adolescents. This calls for regularly performed
      blood pressure assessment and monitoring in the adolescent population. It is
      recommended to focus on obesity prevention and socioeconomic health inequalities
      by further trying to improve living and working conditions in adverse rural
      environments.

PMID- 25956274
TI  - Propofol-alfentanyl versus midazolam-alfentanyl in inducing procedural amnesia of
      upper gastrointestinal endoscopy in children--blind randomised trial.
AB  - In paediatric patients, esophagogastroduodenoscopy (EGD) is commonly performed
      with the use of sedation. The aim of the study was to compare the effectiveness
      of propofol and midazolam in providing procedural amnesia and controlling
      behaviour in children undergoing diagnostic EGD. Children (9-16 years),
      classified to the first or second class of the American Society of
      Anaesthesiologists' physical status classification referred for EGD, were
      randomly assigned to receive propofol with alfentanyl or midazolam with
      alfentanyl for sedation during the procedure. Within 120 min after the procedure,
      patients were repeatedly investigated for memory of the procedure and for memory
      of pain intensity during EGD with the use of the visual analogue scale. Activity
      and cooperation of the patient during the procedure was assessed with the
      relative adequacy scale. Of the 51 children, 48 completed the study. Propofol was
      significantly better than midazolam in inducing amnesia of procedural pain (mean
      difference 11.53 mm; 95 % confidence interval [CI] 0.96 to 22.10), loss of memory
      of the procedure (relative risk 0.4; 95 % CI 0.21 to 0.59) and controlling
      behaviour (relative risk 2.12; 95 % CI 1.33 to 3.36). CONCLUSION: In children
      sedated for EGD, propofol is significantly better than midazolam at providing
      procedural amnesia and controlling behaviour during the procedure.

PMID- 25956275
TI  - Influence of body mass index status on urinary creatinine and specific gravity
      for epidemiological study of children.
AB  - In epidemiological studies, urinary biomonitoring is a valid approach to assess
      the association between environmental chemical exposure and children's health.
      Many clinical biomarkers (e.g., endogenous metabolites) are also based on
      analysis of urine. Considering the variability in urinary output, urinary
      concentrations of chemicals are commonly adjusted by creatinine and specific
      gravity (SG). However, there is a lack of systematic evaluation of their
      appropriateness for children. Furthermore, urinary SG and creatinine excretion
      could be influenced by body mass index (BMI), but the effect of BMI status on the
      two correction factors is unknown. We measured SG and creatinine concentrations
      of repeated first morning urine samples collected from 243 primary school
      children (8-11 years) over 5 consecutive weekdays. Urinary SG presented a higher
      temporal consistency compared with creatinine. Urinary SG was associated with sex
      (p < 0.001), whereas sex (p =0.034) and BMI (p = 00.008) were associated with
      urinary creatinine levels. Inter-day collection time was not associated with SG
      or creatinine after excluding the effect of Monday as a confounder. When
      stratified by BMI status, none of the factors were associated with creatinine
      among the overweight and obese children. CONCLUSION: Generally, SG is preferable
      for correcting the variability in urinary output for children although creatinine
      correction may also perform well in overweight and obese children. SG correction
      is recommended for epidemiological exposure analysis in children based on urinary
      levels of exogenous or endogenous metabolites.

PMID- 25956276
TI  - Trained breathing-induced oxygenation acutely reverses cardiovascular autonomic
      dysfunction in patients with type 2 diabetes and renal disease.
AB  - AIMS: Cardiovascular autonomic dysfunction, evaluated as baroreflex sensitivity
      (BRS), could be acutely corrected by slow breathing or oxygen administration in
      patients with type 1 diabetes, thus suggesting a functional component of the
      disorder. We tested this hypothesis in patients with the type 2 diabetes with or
      without renal impairment. METHODS: Twenty-six patients with type 2 diabetes (aged
      61.0 +/- 0.8 years, mean +/- SEM; duration of diabetes 10.5 +/- 2 years, BMI 29.9
      +/- 0.7 kg/m(2), GFR 68.1 +/- 5.6 ml/min) and 24 healthy controls (aged 58.5 +/-
      1.0 years) were studied. BRS was obtained from recordings of RR interval and
      systolic blood pressure fluctuations during spontaneous and during slow, deep (6
      breaths/min) controlled breathing in conditions of normoxia or hyperoxia (5 l/min
      oxygen). RESULTS: During spontaneous breathing, diabetic patients had lower RR
      interval and lower BRS compared with the control subjects (7.1 +/- 1.2 vs. 12.6
      +/- 2.0 ms/mmHg, p < 0.025). Deep breathing and oxygen administration
      significantly increased arterial saturation, reduced RR interval and increased
      BRS in both groups (to 9.6 +/- 1.8 and 15.4 +/- 2.4 ms/mmHg, respectively, p <
      0.05, hyperoxia vs. normoxia). Twelve diabetic patients affected by chronic
      diabetic kidney disease (DKD) presented a significant improvement in the BRS
      during slow breathing and hyperoxia (p < 0.025 vs. spontaneous breathing during
      normoxia). CONCLUSIONS: Autonomic dysfunction present in patients with type 2
      diabetes can be partially reversed by slow breathing, suggesting a functional
      role of hypoxia, also in patients with DKD. Interventions known to relieve tissue
      hypoxia and improve autonomic function, like physical activity, may be useful in
      the prevention and management of complications in patients with diabetes.

PMID- 25956277
TI  - Association between GT-repeat polymorphism at heme oxygenase-1 gene promoter and
      gastric cancer and metastasis.
AB  - HO-1 gene encodes heme oxygenase-1 enzyme that catalyzes the oxidation of heme to
      carbon monoxide (CO). It has also been suggested that cells could be protected by
      the enzyme against stress. A (GT) n dinucleotide repeat at HO-1 promoter is a
      polymorphic region and modulates gene transcription and associated with some of
      diseases. In this study, length of polymorphism GT tandem repeat has been
      determined and classified into two alleles short (<=28) and long (>=29). In
      present study, association between GT-repeat polymorphism at heme oxygenase-1
      gene promoter and increased risk of gastric cancer and metastasis was
      investigated. Blood samples from 100 control individuals and 60 gastric cancer
      cases had taken. Genotypic frequencies of (GT) n repeat for samples were
      determined using PCR technique and polyacrylamide PAGE electrophoresis. At final,
      higher frequency alleles were sequenced. Our results show that S-allele is
      significantly higher in cases in comparison with control groups (p = 0/000, odds
      ratio (OR) = 4/154). It has been shown that individuals with S/S and S/L
      genotypes are at high risk of having gastric cancer (p = 0/000, OR = 3/789).
      Statistic data show association between SS genotype and risk of gastric cancer
      metastasis (p = 0.017, OR = 3.889). But, there is no significant association
      between clinicopathological characteristics of the patients and risk of gastric
      cancer metastasis (p > 0.05). Significant association was found between short
      allele (SS + SL genotypes) and risk of gastric cancer, and also strong
      association was found between SS genotype and risk of gastric cancer metastasis.

PMID- 25956278
TI  - gamma-Synuclein confers both pro-invasive and doxorubicin-mediated pro-apoptotic
      properties to the colon adenocarcinoma LS 174T cell line.
AB  - gamma-synuclein, a neuronal protein of the synuclein family, is involved in
      carcinogenesis. To investigate its role in colorectal cancer carcinogenesis, we
      overexpressed gamma-synuclein in LS 174T colon adenocarcinoma cell line (termed
      LS 174T-gammasyn). When compared with untransfected/mock transfectants, LS 174T
      gammasyn had higher mobility in scratch wound assay, tend to scatter more in cell
      scattering assay, and had enhanced lamellipodia and filopodia formation in cell
      spreading assay. Enhanced adhesion of LS 174T-gammasyn to fibronectin and
      collagen and significantly higher proliferation rate showed that gamma-synuclein
      was able to increase extracellular matrix interaction and promoted proliferation
      of LS 174T. Higher invasiveness of LS 174T-gammasyn was evidenced by enhanced
      invasion to the bottom of the basement membrane in Boyden chamber assay. However,
      LS 174T-gammasyn were significantly more vulnerable to doxorubicin, vincristine
      and hydrogen peroxide insults, via apoptotic cell death. LS 174T-gammasyn also
      had reduced anchorage-independent growth as shown by reduced colony formation and
      reduced anoikis resistance. We found that overexpression of gamma-synuclein
      confers both pro-invasive and doxorubicin-mediated pro-apoptotic properties to LS
      174T, where the former was mediated through enhanced cyclic adenosine
      monophosphate response element binding protein (CREB) phosphorylation, while the
      latter involved hepatocyte growth factor (HGF) downregulation and subsequent
      downstream signalling pathways possibly involving extracellular signal-regulated
      kinases (ERK)1/2, p38alpha, c-Jun N-terminal kinase (JNK) pan and Signal
      Transducers and Activators of Transcription (STATs). This unexpected contrasting
      finding as compared to other similar studies on colon cancer cell lines might be
      correlated with the degree of tumour advancement from which the cell lines were
      derived from.

PMID- 25956279
TI  - Homocysteine: new tumor marker in pleural fluid.
AB  - There are no published studies examining the utility of total homocysteine (HCY)
      in pleural fluid. The aim was to measure the accuracy of pleural fluid HCY
      concentration for diagnosis of malignant pleural effusion (MPE). We studied
      pleural fluids obtained by thoracocentesis in patients with pleural effusion.
      Pleural fluid HCY concentration was measured by immunonephelometry using N Latex
      HCY reagent with monoclonal antibody in automated analyzers BNII (Siemens
      Diagnostics(r)). Patients were classified into two groups according to the
      etiology of pleural effusion: benign pleural effusions (BPE) and MPE. Pleural
      effusion was categorized as MPE if malignant cells were demonstrated in pleural
      fluid or pleural biopsy. The accuracy of pleural fluid HCY concentration for
      diagnosis of MPE was determined using receiver operating characteristic (ROC)
      techniques by analyzing the area under the ROC curve (AUC). We studied 89
      patients with ages between 1 and 96 years old (median = 66). Forty-eight patients
      were BPE and 41 were MPE. Pleural fluid HCY concentration was significantly
      higher in patients with MPE (median = 13.70 MUmol/L) than in those with BPE
      (median = 8.05 MUmol/L). The AUC value was 0.833 (95 % confidence interval (CI)
      0.739-0.903). The optimal cutoff value was 13.1 MUmol/L exhibiting 56.1 % (95 %
      CI 39.8-71.5) sensitivity and 85.4 % (95 % CI 72.2-93.9) specificity. Pleural
      fluid HCY concentration showed high diagnostic accuracy to predict whether a
      pleural effusion is benign or malignant. Pleural fluid HCY concentration may be
      measured easily and quickly in automated analyzers and could be a tumor marker
      commonly used for diagnosis of MPE.

PMID- 25956281
TI  - Teruhisa Kazui (18 May 1941-8 February 2015): a giant of aortic surgery.

PMID- 25956280
TI  - Long-term results of fractionated stereotactic radiotherapy as third-line
      treatment in acromegaly.
AB  - The treatment of acromegaly is based on surgery, drugs, and radiotherapy as a
      third-line option. Fractionated stereotactic radiotherapy (FSRT) is a new
      technique with a need for long-term evaluation. The purpose of the study was to
      evaluate long-term results of FSRT in acromegaly. Overall, 34 patients [sex ratio
      1.12, age 45 (5-65) years] with a pituitary adenoma of 24.5 (9-76) mm including
      20 invasive tumors were treated by radiotherapy in fractionated stereotactic
      conditions delivering 50 gy in 27 sessions. Baseline growth hormone (GH) and IGF1
      levels were 18 (+/-14.5) and 632.6 (+/-339) ug/L, respectively. Indications of
      FSRT were failure of surgery and drug treatments (n = 30) or
      contraindication/refusal of surgery (n = 4). Hormonal control was defined by
      normal age- and sex-adjusted IGF1. Remission was defined by hormonal control
      after withdrawal of drugs for a minimum of three consecutive months. Data were
      analyzed in SPSS software with a significance level at p < 0.05. After a mean
      follow-up of 152 months, hormonal control was achieved in 33 patients (97 %) with
      withdrawal of drugs in 13 patients (38.2 %) without any recurrence. Factors found
      to be significantly associated to remission in a multivariate Cox regression were
      lower baseline hormone levels (GH and IGF1) and smaller tumor size. Tumor control
      was achieved in all patients. Acquired hypopituitarism after radiotherapy was the
      main side effect reported with a rate of 39 %. FSRT seems to be an effective and
      well tolerated third-line treatment of acromegaly, particularly adapted to macro
      adenomas treatment.

PMID- 25956282
TI  - Impact of interactive voice response technology on primary adherence to
      bisphosphonate therapy: a randomized controlled trial.
AB  - Osteoporosis (weak bones) is a disorder that has high morbidity, mortality, and
      healthcare utilization. Effective treatment is available for this disorder, but
      many patients choose not to start therapy. This is the first study showing an
      intervention that increases the initiation rates to medications for osteoporosis.
      INTRODUCTION: One out of six patients prescribed an oral bisphosphonate does not
      initiate therapy, a phenomenon known as primary non-adherence. Reasons for
      bisphosphonate primary non-adherence have been identified, but not interventions
      that positively impact primary adherence rates. The purpose of this study is to
      determine the effectiveness of interactive voice response technology to improve
      oral bisphosphonate primary adherence. METHODS: This was a prospective,
      randomized controlled trial conducted in January-December 2014 at Kaiser
      Permanente Colorado, an integrated healthcare system. Adults with a new oral
      bisphosphonate prescription for osteoporosis or osteopenia which was not
      purchased within 14-20 days of being ordered were included. There were 127 and
      118 patients in the intervention group and control groups, respectively. The
      intervention group received an interactive voice response phone call followed by
      a letter 1 week later if primary non-adherence continued, whereas the control
      group did not receive any outreach. The primary outcome was the proportion of
      patients who purchased their oral bisphosphonate within 25 days of randomization.
      RESULTS: There were 62/127 (48.8%) intervention patients and 36/118 (30.5%)
      control patients who purchased their bisphosphonate prescription within 25 days
      of randomization (OR = 2.17, 95% CI 1.29-3.67). When adjusted for age, sex,
      history of bone mineral density scan and fracture, the odds ratio for
      intervention versus control group was 2.3 (95% CI 1.34-3.94). CONCLUSION: An
      interactive voice response phone call and follow-up letter significantly improved
      primary adherence to oral bisphosphonate therapy. Such an intervention could be
      considered for improving primary adherence rates to other medication classes.

PMID- 25956283
TI  - Effect of vitamin D supplementation alone on muscle function in postmenopausal
      women: a randomized, double-blind, placebo-controlled clinical trial.
AB  - The present study investigates the effects of vitamin D on muscle function in
      postmenopausal women. It has been shown that vitamin D supplementation in
      postmenopausal women with hypovitaminosis D provides significant protective
      factor against sarcopenia, with significant increases in muscle strength and
      control of progressive loss of lean mass. INTRODUCTION: We aimed to evaluate the
      effect of supplementation of vitamin D (VITD) alone on muscle function in younger
      postmenopausal women. METHODS: In this double-blind, placebo-controlled clinical
      trial, 160 Brazilian postmenopausal women were randomized into two groups: VITD
      group consisting of patients receiving vitamin D3 1000 IU/day orally (n = 80) or
      placebo group (n = 80). Women with amenorrhea for more than 12 months and age 50
      65 years, with a history of falls (previous 12 months), were included. The
      intervention time was 9 months, with assessments at two points, start and end.
      Lean mass was estimated by total-body dual-energy X-ray absorptiometry (DXA) and
      muscle strength by handgrip strength and chair rising test. The plasma
      concentrations of 25-hydroxyvitamin D [25(OH)D] were measured by high-performance
      liquid chromatography (HPLC). Statistical analysis was by intention to treat
      (ITT), using ANOVA, Student's t test, and Tukey's test. RESULTS: After 9 months,
      average values of 25(OH)D increased from 15.0 +/- 7.5 to 27.5 +/- 10.4 ng/ml
      (+45.4%) in the VITD group and decreased from 16.9 +/- 6.7 to 13.8 +/- 6.0 ng/ml
      (-18.5%) in the placebo group (p < 0.001). In the VITD group, there was
      significant increase in muscle strength (+25.3%) of the lower limbs by chair
      rising test (p = 0.036). In women in the placebo group, there was considerable
      loss (-6.8%) in the lean mass (p = 0.030). CONCLUSION: The supplementation of
      vitamin D alone in postmenopausal women provided significant protective factor
      against the occurrence of sarcopenia, with significant increases in muscle
      strength and control of progressive loss of lean mass.

PMID- 25956284
TI  - Low pulmonary function is related with a high risk of sarcopenia in community
      dwelling older adults: the Korea National Health and Nutrition Examination Survey
      (KNHANES) 2008-2011.
AB  - Sarcopenia is the age-related reduction of skeletal muscle mass in older
      individuals. Respiratory muscle strength may be related to skeletal muscle mass
      and, thus, the present study attempted to estimate the risk of sarcopenia
      relative to decreased pulmonary function. The present findings demonstrated that
      low pulmonary function was associated with low muscle mass in community-dwelling
      older adults. INTRODUCTION: Lean body mass is related to pulmonary function in
      patients with chronic obstructive pulmonary disease (COPD). However, the
      relationship between muscle mass and pulmonary function in healthy older adults
      has yet to be clarified. Thus, the present study investigated the association of
      pulmonary function with muscle mass in an older community-dwelling Korean
      population. METHODS: This study included 463 disease-free subjects over 65 years
      of age who underwent anthropometric measurements, laboratory tests, spirometry,
      and the estimation of appendicular skeletal muscle (ASM) mass in the 2008-2011
      Korea National Health and Nutrition Examination Survey (KNHANES). Low muscle mass
      was defined as the value of ASM divided by height squared (ASM/height(2)) that
      was less than two standard deviations (SD) below the sex-specific mean of the
      young reference group. RESULTS: Forced expiratory volume in 1 s (FEV1[L]) and
      forced vital capacity (FVC[L]) were positively correlated with ASM/height(2) in
      males (p < 0.001 and p = 0.001, respectively) but not in females (p = 0.360 and p
      = 0.779, respectively). A univariate logistic regression analysis revealed that
      males with low FEV1 or FVC were more likely to have low muscle mass (odds ratio
      [OR] = 3.11, 95% confidence interval [CI] 1.62-5.99 for FEV1; OR = 1.99, 95% CI
      1.13-3.53 for FVC); similar results were found for females, but the significance
      was lower (OR = 11.37, 95% CI 0.97-132.91 for FEV1; OR = 7.31, 95% CI 1.25-42.74
      for FVC). After adjusting for age, smoking, and moderate physical activity, a low
      FEV1 value was associated with low muscle mass in both males (OR = 2.90, 95% CI
      1.50-5.63) and females (OR = 9.15, 95% CI 1.53-54.77). CONCLUSIONS: Using
      nationally representative data from the 2008-2011 KNHANES, low pulmonary function
      was found to be associated with low muscle mass in community-dwelling older
      Korean adults.

PMID- 25956285
TI  - Bone structure assessed by HR-pQCT, TBS and DXL in adult patients with different
      types of osteogenesis imperfecta.
AB  - Bone microarchitecture by high-resolution peripheral quantitative computed
      tomography (HR-pQCT) was assessed in adult patients with mild, moderate, and
      severe osteogenesis imperfecta (OI). The trabecular bone score (TBS), bone
      mineral density (BMD) by dual-energy X-ray absorptiometry (DXA), and dual X-ray
      and laser (DXL) at the calcaneus were likewise assessed in patients with OI.
      Trabecular microstructure and BMD in particular were severely altered in patients
      with OI. INTRODUCTION: OI is characterized by high fracture risk but not
      necessarily by low BMD. The main purpose of this study was to assess bone
      microarchitecture and BMD at different skeletal sites in different types of OI.
      METHODS: HR-pQCT was performed in 30 patients with OI (mild OI-I, n = 18 (41.8
      [34.7, 55.7] years) and moderate to severe OI-III-IV, n = 12 (47.6 [35.3, 58.4]
      years)) and 30 healthy age-matched controls. TBS, BMD by DXA at the lumbar spine
      and hip, as well as BMD by DXL at the calcaneus were likewise assessed in
      patients with OI only. RESULTS: At the radius, significantly lower trabecular
      parameters including BV/TV (p = 0.01 and p < 0.0001, respectively) and trabecular
      number (p < 0.0001 and p < 0.0001, respectively) as well as an increased
      inhomogeneity of the trabecular network (p < 0.0001 and p < 0.0001, respectively)
      were observed in OI-I and OI-III-IV in comparison to the control group. Similar
      results for trabecular parameters were found at the tibia. Microstructural
      parameters were worse in OI-III-IV than in OI-I. No significant differences were
      found in cortical thickness and cortical porosity between the three subgroups at
      the radius. The cortical thickness of the tibia was thinner in OI-I (p < 0.001),
      but not OI-III-IV, when compared to controls. CONCLUSIONS: Trabecular BMD and
      trabecular bone microstructure in particular are severely altered in patients
      with clinical OI-I and OI-III-IV. Low TBS and DXL and their significant
      associations to HR-pQCT parameters of trabecular bone support this conclusion.

PMID- 25956286
TI  - A double-blind, randomized, Phase III, multicenter study in 358 pediatric
      subjects receiving isotretinoin therapy demonstrates no effect on pediatric bone
      mineral density.
AB  - This study compared the effects of pediatric acne treatment with two isotretinoin
      formulations on bone mineral density. We demonstrated no difference in the effect
      of the two formulations. No effect on pediatric bone mineral density was
      identified for either formulation. INTRODUCTION: Isotretinoin (13-cis-retinoic
      acid) is a treatment for recalcitrant nodular acne with a purported effect on
      bone mineral density (BMD). The side effects of isotretinoin on vertebral bone
      were evaluated to assess the safety of a new FDA-approved isotretinoin
      formulation: Lidose-isotretinoin (Cip-Iso). METHODS: This double-blind,
      randomized, phase III, active control, parallel-group, multicenter study compared
      the safety, efficacy, and non-inferiority of CIP-Iso to a marketed reference
      product, Accutane(r), in severe recalcitrant nodular acne subjects. Three hundred
      fifty-eight pediatric male and female subjects aged between 12 and 17 years
      underwent 20 weeks of treatment with PA lumbar spine dual X-ray absorptiometry
      (DXA) measurements obtained for bone mineral density (BMD) and Z-scores, 5.5
      months apart on visits 1 and 8. One hundred sixty-eight of 358 subjects had
      height adjusted Z-scores (HAZ) calculated. RESULTS: There was no difference in
      the least squares (LS) mean Z-score or HAZ of the two drugs at visit 1 or 8. The
      mean and LS mean Z-score and HAZ were greater than zero at visits 1 and 8 for
      both drugs. The change in the LS mean spine Z-score, but not HAZ, between visits,
      was statistically significant for both drugs. There was a mean increase in BMD
      (g/cm(2)) for both products between visits. CONCLUSIONS: There is no difference
      in the effect of two formulations of isotretinoin on spine bone density after 6
      months of treatment. BMD increased and the small change in spine Z-score over
      treatment disappeared after height adjustment. Mean positive Z-scores and HAZ in
      the study were likely due to the exclusion of low and inclusion of high Z-score
      subjects.

PMID- 25956287
TI  - Quality of life in patients with venous thromboembolism and atrial fibrillation
      treated with coumarin anticoagulants.
AB  - INTRODUCTION: Little is known about the overall quality of life (QOL) in patients
      newly diagnosed with venous thromboembolism (VTE) and atrial fibrillation (AF).
      We studied QOL in patients with VTE and AF immediately after the start of
      anticoagulant therapy, and after three months of treatment. Furthermore we
      identified whether QOL was affected by age, gender and nationality. MATERIALS AND
      METHODS: The European pharmacogenetics of anticoagulant therapy (EU-PACT) study
      was a multicentre, randomized controlled trial of patients aged >18years
      diagnosed with VTE or AF. QOL was assessed using EuroQol 5 dimensions (EQ-5D)
      questionnaires. RESULTS: The EQ-5D questionnaires were completed by 187 patients
      with VTE and 660 patients with AF. The QOL in patients diagnosed with VTE or AF
      was significantly impaired, however, during a 3months treatment period, patients
      experienced an improvement (p<0.05). The QOL in patients diagnosed with VTE
      improved with increasing age, with similar effects seen in men and women. Men and
      women diagnosed with AF differed in QOL (respectively 0.84 and 0.74, p<0.05), and
      QOL decreased with age. Comparison between countries showed significant
      differences in the EQ-Index score at follow-up of patients with VTE, and in both
      EQ-Index score and EQ-VAS of patients with AF. CONCLUSIONS: The QOL in patients
      with VTE and AF is strongly reduced directly after the start of anticoagulant
      treatment, but improves within 3months. Moreover, QOL is influenced by
      demographic and disease-specific variables. These findings provide useful
      information for future cost-effectiveness studies.

PMID- 25956288
TI  - Establishing a reference range for thrombin generation using a standard plasma
      significantly improves assay precision.
AB  - BACKGROUND: Thrombin generation is a global coagulation assay which appears to be
      an effective method for assessing the potential for an individual's plasma to
      coagulate. However for this assay to become accepted in routine clinical practice
      it requires standardization. OBJECTIVES: To establish a reference range for the
      NIBSC reference plasma (TGT-RP) which can then become an internal quality control
      (IQC) for thrombin generation assays. PATIENTS/METHODS: Thrombin generation was
      measured in TGT-RP in 153 independent experiments using 4 assay conditions; 1 pM
      tissue factor (TF) or 5 pM TF +/- thrombomodulin (TM). A target value +/- 2 SD
      was calculated to provide an acceptance range under the 4 conditions. A plasma
      sample from a healthy volunteer was subsequently tested in 11 separate
      experiments using the TGT-RP for (i) normalisation and (ii) exclusion of
      experimental results when the TGT-RP results did not fall within the established
      acceptance range. RESULTS: An acceptance range was established for TGT-RP for the
      4 assay conditions. Normalisation of all results from a healthy volunteer reduced
      inter-assay variability significantly (ETP: p=0.0003; Peak: p=0.001). Exclusion
      of results from the volunteer when concurrently run TGT-RP results fell outside
      the acceptance range reduced inter-assay variability significantly when reporting
      raw data (ETP: p=0.001; Peak: p=0.004). However normalisation of this data had no
      beneficial effect (ETP: p=0.126; Peak: p=0.232). CONCLUSIONS: Our work represents
      further progress in the standardization of thrombin generation techniques with
      the establishment of an IQC reference range. Using an IQC reduces inter-assay
      variability, whilst allowing reporting of raw data and ensures production of
      accurate and reproducible data.

PMID- 25956289
TI  - Sexual (Minority) Trajectories, Mental Health, and Alcohol Use: A Longitudinal
      Study of Youth as They Transition to Adulthood.
AB  - Lesbian, gay, bisexual, and queer/questioning youth health disparities are well
      documented; however, study limitations restrict our understanding of how the
      temporal interplay among domains of sexuality (attraction, behavior, and
      identity) situate individuals to be more or less at risk for poor mental health
      and alcohol use across the transition to adulthood. Four waves of data from the
      National Longitudinal Study of Adolescent to Adult Health (n = 12,679; 51.29 %
      female) were used with repeated measures latent class analysis to estimate sexual
      trajectory groups designated by prospective reports of romantic attraction,
      sexual/romantic behavior, and sexual identity from adolescence to adulthood. Five
      unique trajectories emerged: two heterosexual groups (heterosexual early daters
      [58.37 %] and heterosexual later daters [29.83 %]) and three sexual minority
      groups (heteroflexible [6.44 %], later bisexually identified [3.32 %], and LG[B]
      identified [2.03 %]). These sexual trajectories differentiate risk for depressive
      symptomology, suicidal thoughts and behaviors, and alcohol use during adolescence
      and early adulthood. Groups where individuals first reported same-sex attraction
      and sexual minority identities in adulthood (heteroflexible and later bisexually
      identified) had similar levels of depression, suicidality, and greater substance
      use than those who largely reported same-sex attraction and behavior during
      adolescence (the LG[B] identified group). These later recognition groups showed
      greater risk for poor outcomes in waves where they also first reported these
      changes in attraction, behaviors, and identities. The emergence of three sexual
      minority groups reveal within-group differences in sexuality and sexual
      trajectories and how these experiences relate to risk and timing of risk across
      the transition to adulthood. 

PMID- 25956291
TI  - Parental Influences on Adolescents' Negative Attitudes Toward Immigrants.
AB  - Attitudes toward immigrants are a core component of adolescents' social
      identities. Although in a globalized world positive attitudes are functional,
      negative views toward immigrant are widespread. This study investigates the
      parent-adolescent transmission of attitudes toward immigrants between age 12 and
      16. In a longitudinal five-wave cohort-sequential multi-informant survey study on
      German adolescents (N = 1289; 52.9 % female) and their parents (mothers N = 772;
      fathers N = 654), self-reported attitudes toward immigrants were measured at each
      time point. Changes in the adolescents' attitudes were predicted by maternal and
      paternal self-reported attitudes across time. Predictions of short-term changes
      revealed that the major effect of the parents' attitudes takes place in early
      adolescence (between grade 6 and 7). The prediction of the adolescents' long-term
      attitude changes indicates that these effects sustain until the age of 16. No
      between-parent differences were found. The results are discussed in terms of
      early adolescence being a sensitive period for parental effects on the
      development of adolescents' attitudes toward immigrants. 

PMID- 25956290
TI  - DRD4 Genotype and the Developmental Link of Peer Social Preference with Conduct
      Problems and Prosocial Behavior Across Ages 9-12 Years.
AB  - The peer environment is among the most important factors for children's
      behavioral development. However, not all children are equally influenced by their
      peers, which is potentially due to their genetic make-up. The dopamine receptor
      D4 gene (DRD4) is a potential candidate gene that may influence children's
      susceptibility to the peer environment. In the present study, we explored whether
      variations in the DRD4 gene moderated the association between children's social
      standing in the peer group (i.e., social preference among classmates) with
      subsequent conduct problems and prosocial behavior among 405 (51% females)
      elementary school children followed annually throughout early adolescence (ages 9
      12 years). The behavioral development of children with and without the DRD4 7
      repeat allele was compared. The results indicated that children who had higher
      positive social preference scores (i.e., who were more liked relative to disliked
      by their peers) showed less conduct problem development in subsequent years
      relative to children who had lower positive social preference scores. In
      contrast, children who had more negative preference scores (i.e., who were more
      disliked relative to liked among peers) showed more conduct problem development
      in subsequent years, relative to children who had less negative preference
      scores. However, these effects only occurred when children had a 7-repeat allele.
      For children who did not have a 7-repeat allele, the level of social preference
      was not associated with subsequent conduct problems. No evidence for gene
      environment interaction effects for prosocial behavior was found. The
      implications for our understanding of conduct problem development and its
      prevention are discussed.

PMID- 25956292
TI  - Detection of a novel herpesvirus from bats in the Philippines.
AB  - Bats are natural hosts of many zoonotic viruses. Monitoring bat viruses is
      important to detect novel bat-borne infectious diseases. In this study, next
      generation sequencing techniques and conventional PCR were used to analyze
      intestine, lung, and blood clot samples collected from wild bats captured at
      three locations in Davao region, in the Philippines in 2012. Different viral
      genes belonging to the Retroviridae and Herpesviridae families were identified
      using next generation sequencing. The existence of herpesvirus in the samples was
      confirmed by PCR using herpesvirus consensus primers. The nucleotide sequences of
      the resulting PCR amplicons were 166-bp. Further phylogenetic analysis identified
      that the virus from which this nucleotide sequence was obtained belonged to the
      Gammaherpesvirinae subfamily. PCR using primers specific to the nucleotide
      sequence obtained revealed that the infection rate among the captured bats was 30
      %. In this study, we present the partial genome of a novel gammaherpesvirus
      detected from wild bats. Our observations also indicate that this herpesvirus may
      be widely distributed in bat populations in Davao region.

PMID- 25956293
TI  - Cell signalling during blastocyst morphogenesis.
AB  - Blastocyst morphogenesis is prepared for even before fertilisation. Information
      stored within parental gametes can influence both maternal and embryonic gene
      expression programmes after egg activation at fertilisation. A complex network of
      intrinsic, cell-cell mediated and extrinsic, embryo-environment signalling
      mechanisms operates throughout cleavage, compaction and cavitation. These
      signalling events not only ensure developmental progression, cell differentiation
      and lineage allocation to inner cell mass (embryo proper) and trophectoderm
      (future extraembryonic lineages) but also provide a degree of developmental
      plasticity ensuring survival in prevailing conditions by adaptive responses.
      Indeed, many cellular functions including differentiation, metabolism, gene
      expression and gene expression regulation are subject to plasticity with short-
      or long-term consequences even into adult life. The interplay between intrinsic
      and extrinsic signals impacting on blastocyst morphogenesis is becoming clearer.
      This has been best studied in the mouse which will be the focus of this chapter
      but translational significance to human and domestic animal embryology will be a
      focus in future years. 

PMID- 25956294
TI  - Amino acids and conceptus development during the peri-implantation period of
      pregnancy.
AB  - The dialogue between the mammalian conceptus (embryo/fetus and associated
      membranes) involves signaling for pregnancy recognition and maintenance of
      pregnancy during the critical peri-implantation period of pregnancy when the
      stage is set for implantation and placentation that precedes fetal development.
      Uterine epithelial cells secrete and/or transport a wide range of molecules,
      including nutrients, collectively referred to as histotroph that are transported
      into the fetal-placental vascular system to support growth and development of the
      conceptus. The availability of uterine-derived histotroph has long-term
      consequences for the health and well-being of the fetus and the prevention of
      Developmental Origins of Health and Disease (DOHAD). Although mechanisms
      responsible for differential growth and development of the conceptus resulting in
      DOHAD phenomena remain unclear, epigenetic events involving methylation of DNA
      are likely mechanisms. Histotroph includes serine and methionine which can
      contribute to the one carbon pool, and arginine, lysine and histidine residues
      which may be targets of methylation. It is also clear that supplementing the diet
      with arginine enhances fetal-placental development in rodents, swine and humans
      through mechanisms that remain to be elucidated. However, molecules secreted by
      conceptuses such as interferon tau in ruminants, estrogens and interferons in
      pigs and chorionic gonadotrophin, along with progesterone, regulate expression of
      genes for nutrient transporters. Understanding mechanisms whereby select
      nutrients regulate expression of genes in cell signaling pathways critical to
      conceptus development, implantation and placentation is required for improving
      successful establishment and maintenance of pregnancy in mammals. 

PMID- 25956295
TI  - The role of hexosamine biosynthesis and signaling in early development.
AB  - Although the culture requirements and the metabolic profile of the
      preimplantation embryo have been thoroughly investigated since their first
      successful culture in a defined medium, now more than 50 years ago (Whitten,
      Nature 177:96, 1956), it is only recently that we have begun to appreciate the
      impact of the environment on life-course trajectory. The mechanisms involved in
      how nutrient availability may potentially modulate developmental potential are
      consequently not well defined. Originally thought of as simple energy substrates
      and biosynthetic precursors, the currently emerging paradigm suggests that
      nutrients may act in non-classical roles to impact on developmental potential.
      This is now an area of considerable activity thanks to pioneering epidemiological
      studies (Barker et al., BMJ 298:564-7, 1989) that have led to the establishment
      of the Developmental Origins of Health and Disease (DoHAD) hypothesis and a whole
      new field of research activity. The period prior to implantation is of particular
      interest as this has been identified as a critical window of developmental
      sensitivity to environmental or nutrient stress (Fleming et al., Biol Reprod
      71:1046-54, 2004a). This review seeks specifically to explore the pivotal role of
      glucose in early mouse development and the mechanisms by which it may impact on
      the cellular functions of the developing embryo. The emerging paradigm suggests
      that this humble hexose sugar may be at the heart of a rather sophisticated
      mechanism of cellular control that not only impacts on cellular proliferation and
      viability in the short term but on cellular memory through to the next
      generation. 

PMID- 25956296
TI  - Molecular biology of the stress response in the early embryo and its stem cells.
AB  - Stress is normal during early embryogenesis and transient, elevated stress is
      commonplace. Stress in the milieu of the peri-implantation embryo is a summation
      of maternal hormones, and other elements of the maternal milieu, that signal
      preparedness for development and implantation. Examples discussed here are
      leptin, adrenaline, cortisol, and progesterone. These hormones signal maternal
      nutritional status and provide energy, but also signal stress that diverts
      maternal and embryonic energy from an optimal embryonic developmental trajectory.
      These hormones communicate endocrine maternal effects and local embryonic effects
      although signaling mechanisms are not well understood. Other in vivo stresses
      affect the embryo such as local infection and inflammation, hypoxia,
      environmental toxins such as benzopyrene, dioxin, or metals, heat shock, and
      hyperosmotic stress due to dehydration or diabetes. In vitro, stresses include
      shear during handling, improper culture media and oxygen levels,
      cryopreservation, and manipulations of the embryo to introduce sperm or
      mitochondria. We define stress as any stimulus that slows stem cell accumulation
      or diminishes the ability of cells to produce normal and sufficient parenchymal
      products upon differentiation. Thus stress deflects downwards the normal
      trajectories of development, growth and differentiation. Typically stress is
      inversely proportional to embryonic developmental and proliferative rates, but
      can be proportional to induction of differentiation of stem cells in the peri
      implantation embryo. When modeling stress it is most interesting to produce a
      'runting model' where stress exposures slow accumulation but do not create
      excessive apoptosis or morbidity. Windows of stress sensitivity may occur when
      major new embryonic developmental programs require large amounts of energy and
      are exacerbated if nutritional flow decreases and removes energy from the normal
      developmental programs and stress responses. These windows correspond to zygotic
      genome activation, the large mRNA program initiated at compaction, ion pumping
      required for cavitation, the differentiation of the first lineages, integration
      with the uterine environment at implantation, rapid proliferation of stem cells,
      and production of certain lineages which require the highest energy and are most
      sensitive to mitochondrial inhibition. Stress response mechanisms insure that
      stem cells for the early embryo and placenta survive at lower stress exposures,
      and that the organism survives through compensatory and prioritized stem cell
      differentiation, at higher stress exposures. These servomechanisms include a
      small set of stress enzymes from the 500 protein kinases in the kinome; the part
      of the genome coding for protein kinases that hierarchically regulate the
      activity of other proteins and enzymes. Important protein kinases that mediate
      the stress response of embryos and their stem cells are SAPK, p38MAPK, AMPK,
      PI3K, Akt, MEK1/2, MEKK4, PKA, IRE1 and PERK. These stress enzymes have cytosolic
      function in cell survival at low stress exposures and nuclear function in
      modifying transcription factor activity at higher stress exposures. Some of the
      transcription factors (TFs) that are most important in the stress response are
      JunC, JunB, MAPKAPs, ATF4, XBP1, Oct1, Oct4, HIFs, Nrf2/KEAP, NFKB, MT1, Nfat5,
      HSF1/2 and potency-maintaining factors Id2, Cdx2, Eomes, Sox2, Nanog, Rex1, and
      Oct4. Clearly the stress enzymes have a large number of cytosolic and nuclear
      substrates and the TFs regulate large numbers of genes. The interaction of stress
      enzymes and TFs in the early embryo and its stem cells are a continuing central
      focus of research. In vitro regulation of TFs by stress enzymes leads to
      reprogramming of the stem cell when stress diminishes stem cell accumulation.
      Since more differentiated product is produced by fewer cells, the process
      compensates for fewer cells. Coupled with stress-induced compensatory
      differentiation of stem cells is a tendency to prioritize differentiation by
      increasing the first essential lineage and decreasing later lineages. These
      mechanisms include stress enzymes that regulate TFs and provide stress-specific,
      shared homeostatic cellular and organismal responses of prioritized
      differentiation. 

PMID- 25956297
TI  - Survival signalling in the preimplantation embryo.
AB  - The development of the preimplantation embryo (from fertilisation until the
      formation of the differentiated blastocyst) occurs without a requirement for
      exogenous mitogenic or survival signals. This distinguishes the behaviour of
      cells in the early embryo from all other normal cells. The discovery that
      fertilisation triggers the production and release of potent bioactive mediators
      by the embryo that act back on membrane receptors demonstrated the presence of
      closed autocrine embryotrophic loops. It is now clear that these ligands act in
      concert with paracrine mediators normally present within the reproductive tract
      to support the normal development of the embryo. These ligands act via receptors
      expressed by the embryo to activate signalling transduced by 1-o
      phosphatidylinositol-3-kinase and the resultant formation of phosphatidylinositol
      3,4,5-trisphosphate. This polyphosphorylated membrane phospholipid acts as a
      docking site for proteins possessing the PH domain. These include PDK1, AKT and
      phospholipase C. The activation of these proteins accounts for the initiation of
      new transcription from the embryonic genome to form a pro-survival, anti
      apoptotic transcriptome and the post-transcriptional activation of pro-survival
      signalling within embryonic cells. This includes the attenuation of action of pro
      apoptotic signals, such as P53. The production of embryotrophic ligands after
      fertilisation bootstraps development by the activation of transcription from the
      embryonic genome, followed by the activation of pro-survival settings within
      embryo cells. 

PMID- 25956298
TI  - Intracellular Ca2+ signaling and preimplantation development.
AB  - The key, versatile role of intracellular Ca2+ signaling during egg activation
      after fertilization has been appreciated for several decades. More recently,
      evidence has accumulated supporting the concept that cytoplasmic Ca2+ is also a
      major signaling nexus during subsequent development of the fertilized ovum. This
      chapter will review the molecular reactions that regulate intracellular Ca2+
      levels and cell function, the role of Ca2+ signaling during egg activation and
      specific examples of repetitive Ca2+ signaling found throughout pre- and peri
      implantation development. Many of the upstream and downstream pathways utilized
      during egg activation are also critical for specific processes that take place
      during embryonic development. Much remains to be done to elucidate the full
      complexity of Ca2+ signaling mechanisms in preimplantation embryos to the level
      of detail accomplished for egg activation. However, an emerging concept is that
      because this second messenger can be modulated downstream of numerous receptors
      and is able to bind and activate multiple cytoplasmic signaling proteins, it can
      help the coordination of development through up- and downstream pathways that
      change with each embryonic stage.

PMID- 25956299
TI  - Female tract cytokines and developmental programming in embryos.
AB  - In the physiological situation, cytokines are pivotal mediators of communication
      between the maternal tract and the embryo. Compelling evidence shows that
      cytokines emanating from the oviduct and uterus confer a sophisticated mechanism
      for 'fine-tuning' of embryo development, influencing a range of cellular events
      from cell survival and metabolism, through division and differentiation, and
      potentially exerting long-term impact through epigenetic remodelling. The balance
      between survival agents, including GM-CSF, CSF1, LIF, HB-EGF and IGFII, against
      apoptosis-inducing factors such as TNFalpha, TRAIL and IFNg, influence the course
      of preimplantation development, causing embryos to develop normally, adapt to
      varying maternal environments, or in some cases to arrest and undergo demise.
      Maternal cytokine-mediated pathways help mediate the biological effects of embryo
      programming, embryo plasticity and adaptation, and maternal tract quality
      control. Thus maternal cytokines exert influence not only on fertility and
      pregnancy progression but on the developmental trajectory and health of
      offspring. Defining a clear understanding of the biology of cytokine networks
      influencing the embryo is essential to support optimal outcomes in natural and
      assisted conception. 

PMID- 25956300
TI  - [Drug use and driving].
AB  - Some drugs are known to impair driving because they can change the vision or
      hearing, and/or disrupt the intellectual or motor abilities: impaired vigilance,
      sedation, disinhibition effect, the coordination of movement disorders and the
      balance. The doctor during prescribing and the pharmacist during deliverance of
      drug treatment should inform their patients of the potential risks of drugs on
      driving or operating machinery. The driver has direct responsibility, who hired
      him and him alone, to follow the medical advice received. The pictograms on the
      outer packaging of medicinal products intended to classify substances according
      to their risk driving: The driver can whether to observe simple precautions
      (level one "be prudent"), or follow the advice of a health professional (level
      two "be very careful"), or if it is totally not drive (level three "danger
      caution: do not drive"). This classification only evaluates the intrinsic danger
      of drugs but not the individual variability. Medicines should be taken into
      account also the conditions for which the medication is prescribed. It is
      important to inform the patient on several points. 

PMID- 25956301
TI  - [Driving license and mellitus diabetes].
AB  - For the "light group" as for the "heavy group" driving license cannot be issued
      or renewed to the applicant or drivers suffering from a condition that may
      constitute or lead to functional disability jeopardize road safety when driving a
      motor vehicle. The decision to issue or renew the license by the prefectural
      authority is taken on the advice of the departmental medical commission or a
      licensed physician. The decree of August 31, 2010 establishes the list of medical
      conditions incompatible with obtaining or maintaining the driving license or
      which may give rise to the issue of driving license limited validity. "Diabetes
      mellitus treated with medications that can cause hypoglycemia" belongs to this
      list. If the medical control of driving ability comes at the initiative of the
      user, the treating physician should firstly ensure the understanding of
      prescribed treatments that can cause hypoglycaemic episodes and other by
      informing diabetic person she must pass a medical examination of fitness to drive
      in a licensed physician. 

PMID- 25956302
TI  - Total thyroidectomy versus lobectomy as initial operation for small unilateral
      papillary thyroid carcinoma: A meta-analysis.
AB  - INTRODUCTION: Consensus guidelines have recommended total thyroidectomy for
      papillary thyroid carcinoma (PTC) > 1 cm. However, the optimal surgical approach
      for small and unilateral (<=1 cm) PTC remains controversial. METHODS: A meta
      analysis was performed using MEDLINE and EMBASE databases to identify all studies
      investigating at thyroid surgery options, total thyroidectomy (TT) versus thyroid
      lobectomy (TL), for PTC <= 1 cm. The primary endpoints were locoregional
      recurrence and mortality rates. RESULTS: The initial literature search identified
      305 publications (1980-2014). Six studies met the inclusion criteria comprising
      2939 patients (2002-2013). Among these patients, 2134 (72.6%) underwent TT and
      805 (27.4%) underwent TL. Mean follow-up was 10.9 +/- 3.4 years (range, 1 month
      to 54 years). Overall, the recurrence rate was 5.4%: 4.4% in the TT group and
      8.3% in the TL group (p < 0.001; RR 0.50, 95% CI 0.37-0.67). The mortality rates
      were 0.3% (8 cases) versus 1.1% (9 cases) in TT and TL groups, respectively (p =
      0.14; RR 0.43, 95% CI 0.17-1.09). CONCLUSION: TT was associated with lower
      recurrence rates, possibly due to a more complete nodal dissection of the central
      neck compartment at the time of initial surgery. Based on these data, it is
      unclear to establish a definitive correlation between the extent of thyroid
      resection and long-term survival rates due to the small number of mortality
      events. However, there is a trend toward lower mortality rates in the TT group.
      Other factors need to be taken into consideration while planning thyroid
      resection for small PTC, such as multifocality, locoregional involvement, mode of
      presentation and age at diagnosis. Refinement of current guidelines for the
      optimal surgical management of PTC <1 cm may be warranted.

PMID- 25956303
TI  - Response of unilamellar DPPC and DPPC:SM vesicles to hypo and hyper osmotic
      shocks: A comparison.
AB  - DPPC and DPPC:SM large unilamellar vesicles (LUVs), prepared by extrusion,
      readily respond to osmotic shocks (hypo- and hyper-osmotic) by water
      influx/efflux (evaluated by changes in turbidity) and by entrapped calcein
      liberation (measured by an increase in dye fluorescence intensity). On the other
      hand, small unilamellar vesicles (SUVs) prepared by sonication are almost
      osmotically insensitive. LUVs water transport, both in hypo- and hyper-osmotic
      conditions, takes place faster than calcein ejection towards the external
      solvent. Similarly, response to a hypotonic imbalance is faster than that
      associated to a hypertonic stress. This difference is particularly noticeable for
      the increase in calcein fluorescence intensity and can be related to the large
      reorganization of the bilayer needed to form pores and/or to adsorb the dye to
      the inner leaflet of the vesicle after water efflux. Conversely, addition of SM
      to the vesicles barely modify the rate of calcein permeation across the bilayer. 

PMID- 25956305
TI  - How to read a receiver operating characteristic curve.

PMID- 25956306
TI  - RNA-Seq Quantification of Hepatic Drug Processing Genes in Germ-Free Mice.
AB  - Intestinal bacteria have been shown to be important in regulating host
      intermediary metabolism and contributing to obesity. However, relatively less is
      known about the effect of intestinal bacteria on the expression of hepatic drug
      processing genes in the host. This study characterizes the expression of hepatic
      drug-processing genes in germ-free (GF) mice using RNA-Seq. Total RNA were
      isolated from the livers of adult male conventional and GF C57BL/6J mice (n = 3
      per group). In the livers of GF mice, the mRNA of the aryl hydrocarbon receptor
      target gene Cyp1a2 was increased 51%, and the mRNA of the peroxisome proliferator
      activated receptor alpha (PPARalpha) target gene Cyp4a14 was increased 202%.
      Conversely, the mRNA of the constitutive androstane receptor (CAR) target gene
      Cyp2b10 was decreased 57%, and the mRNA of the pregnane X receptor target gene
      Cyp3a11 was decreased 87% in GF mice. Although other non-Cyp phase-1 enzymes in
      the livers of GF mice were only moderately affected, there was a marked down
      regulation in the phase-2 enzymes glutathione S-transferases p1 and p2, as well
      as a marked up-regulation in the major bile acid transporters Na(+)-taurocholate
      cotransporting polypeptide and organic anion-transporting polypeptide 1b2, and
      the cholesterol transporter ATP-binding cassette transporter Abcg5/Abcg8. This
      study demonstrates that intestinal bacteria regulate the expression of a large
      number of drug-processing genes, which suggests that intestinal bacteria are
      responsible for some individual differences in drug responses.

PMID- 25956304
TI  - Age-dependent therapeutic effects of liver X receptor-alpha activation in murine
      polymicrobial sepsis.
AB  - The severity of sepsis is significantly affected by advanced age; however, age
      dependent molecular mechanisms of this susceptibility are unknown. Nuclear liver
      X receptor-alpha (LXRalpha) is a regulator of lipid metabolism with associated
      anti-inflammatory properties. Here, we investigated the role of LXRalpha in age
      dependent lung injury and outcome of sepsis. Male C57BL/6, LXRalpha-deficient
      (LXRalpha(-/-)) and wild type (WT) (LXRalpha(+/+)) mice of different ages were
      subjected to sepsis by cecal ligation and puncture (CLP). In pharmacological
      studies, treatment with the LXRalpha ligand T0901317 reduced lung neutrophil
      infiltration in C57BL/6 mice aged from 1 to 8 mo when compared with vehicle
      treated animals subjected to CLP. The LXRalpha ligand improved survival in young
      mice (2-3 mo old) but did not affect survival or neutrophil infiltration in
      mature adult mice (11-13 mo old). Immunoblotting revealed an age-dependent
      decrease of lung LXRalpha levels. Young LXRalpha(-/-) mice (2-3 mo old) exhibited
      earlier mortality than age-matched WT mice after CLP. Lung damage and neutrophil
      infiltration, lung activation of the pro-inflammatory NF-kappaB and plasma IL-6
      levels were higher in LXRalpha(-/-) mice 18 h after CLP compared with
      LXRalpha(+/+) mice. This study suggests that the anti-inflammatory properties of
      LXRalpha in sepsis are age-dependent and severely compromised in mature adult
      animals. 

PMID- 25956307
TI  - Trepopnoea due to aneurysm of the descending thoracic aorta compressing the
      heart: an unusual occurrence.

PMID- 25956308
TI  - Improved false negative rate of axillary status using sentinel lymph node biopsy
      and ultrasound-suspicious lymph node sampling in patients with early breast
      cancer.
AB  - BACKGROUND: The false negative rate of sentinel lymph node biopsy (SLNB) is 5
      10%, and results in improper patient management. The study was to assess the
      value of ultrasound-suspicious axillary lymph node biopsy (USALNB) in patients
      with early breast cancer, and to compare SLNB combined with USALNB (SLNB +
      USALNB) with SLNB alone. METHODS: From January 2010 to July 2013, 216 patients
      with early breast cancer were enrolled consecutively at the Department of Breast
      and Thyroid Surgery, Qianfoshan Hospital, Shandong University. All patients
      underwent wire localization of the suspicious node by color Doppler
      ultrasonography, followed by SLNB 2-3 hours later, suspicious node
      lymphadenectomy, and level >= II axillary dissection (as the gold standard). The
      predictive values of node status between SLNB + USALNB and SLNB alone were
      compared. RESULTS: The success rate of SLNB was 99.1% (214/216). After axillary
      dissection, 71 patients were confirmed with axillary lymph node metastases by
      pathological examinations. Eight false negatives were observed using SLNB alone,
      resulting in sensitivity of 88.7%, specificity of 100%, false negative rate of
      11.3%, and false positive rate of 0% in predicting the axillary node status. SLNB
      + USALNB resulted in sensitivity of 97.2%, specificity of 100%, false negative
      rate of 2.8%, and false positive rate of 0%. The false negative rate of SLNB +
      USALNB was significantly different from that of SLNB alone (P = 0.031).
      CONCLUSIONS: SLNB + USALNB seems to be a low-risk procedure that might be useful
      in reducing the false negative rate of SLNB, improving the accuracy of axillary
      nodes evaluation in early breast cancer.

PMID- 25956310
TI  - Stinging insect allergy: state of the art 2015.
AB  - Stinging insect allergy is responsible for more than 10% of all cases of
      anaphylaxis. The potential culprit insects are diverse and vary with geography.
      The incidence of insect allergy is declining in some areas and increasing in
      others, possibly due to effects of climate change, introduction of species into
      new areas, outdoor recreational activities, and movement of human populations
      that brings insects into contact with a greater number of people. Flying
      Hymenoptera and imported fire ant stings are responsible for the majority of
      patients evaluated for insect anaphylaxis. The most efficient means of
      identifying allergy to insects is skin testing although falsely positive and
      negative results occur. The limitations of testing coupled with the natural
      temporal variability of allergic sensitivity complicate the interpretation of
      test results. The clinical history is of paramount importance to be certain that
      the test results are relevant; therefore, screening or testing before a history
      of a sting reaction is not advisable. Mast cell disorders are associated with
      severe anaphylaxis from insect stings and should be considered in affected
      subjects. Insect immunotherapy, using venoms for most insects and whole-body
      extracts for imported fire ants, is proven effective in reducing the likelihood
      of anaphylaxis due to subsequent stings from 40%-60% to less than 5%. Future
      clinical application of component testing or in vitro cellular tests, such as the
      basophil activation test, may improve optimal choices for immunotherapy.

PMID- 25956309
TI  - Genome-wide association study of susceptibility loci for breast cancer in
      Sardinian population.
AB  - BACKGROUND: Despite progress in identifying genes associated with breast cancer,
      many more risk loci exist. Genome-wide association analyses in genetically
      homogeneous populations, such as that of Sardinia (Italy), could represent an
      additional approach to detect low penetrance alleles. METHODS: We performed a
      genome-wide association study comparing 1431 Sardinian patients with non
      familial, BRCA1/2-mutation-negative breast cancer to 2171 healthy Sardinian blood
      donors. DNA was genotyped using GeneChip Human Mapping 500 K Arrays or Genome
      Wide Human SNP Arrays 6.0. To increase genomic coverage, genotypes of additional
      SNPs were imputed using data from HapMap Phase II. After quality control
      filtering of genotype data, 1367 cases (9 men) and 1658 controls (1156 men) were
      analyzed on a total of 2,067,645 SNPs. RESULTS: Overall, 33 genomic regions (67
      candidate SNPs) were associated with breast cancer risk at the p <  0(-6) level.
      Twenty of these regions contained defined genes, including one already associated
      with breast cancer risk: TOX3. With a lower threshold for preliminary
      significance to p < 10(-5), we identified 11 additional SNPs in FGFR2, a well
      established breast cancer-associated gene. Ten candidate SNPs were selected,
      excluding those already associated with breast cancer, for technical validation
      as well as replication in 1668 samples from the same population. Only SNP
      rs345299, located in intron 1 of VAV3, remained suggestively associated (p-value,
      1.16 x 10(-5)), but it did not associate with breast cancer risk in pooled data
      from two large, mixed-population cohorts. CONCLUSIONS: This study indicated the
      role of TOX3 and FGFR2 as breast cancer susceptibility genes in BRCA1/2-wild-type
      breast cancer patients from Sardinian population.

PMID- 25956311
TI  - When can immunotherapy for insect sting allergy be stopped?
AB  - BACKGROUND: Stings by Hymenoptera (honey bees, vespids, ants) can cause systemic
      allergic reactions (SARs). Venom immunotherapy (VIT) is highly effective and
      reduces an allergic patient's risk of a recurrent SAR to less than 5-20%. The
      risk of a recurrent SAR to a re-sting decreases the longer VIT is continued. The
      recommended duration of VIT is at least 3 to 5 years. RISK FACTORS: Risk factors
      for recurrent SARs to a sting after stopping VIT have been identified and
      discussed: Recommendations concerning stopping VIT: For patients without any of
      the identified risk factors, VIT should be continued for 5 rather than 3 years.
      In patients with definite risk factors, a longer duration of VIT has to be
      discussed before stopping it. In mast cell disorders, VIT for life is
      recommended. Because of the residual risk of SARs after VIT, all patients are
      advised to carry an epinephrine autoinjector indefinitely and to continue to take
      measures to avoid Hymenoptera stings.

PMID- 25956312
TI  - Elevation of the head of bed to treat supraesophageal reflux: controlling the
      trigger and reducing the "drip".

PMID- 25956313
TI  - IgE to Poppy Seed and Morphine Are Not Useful Tools to Diagnose Opiate Allergy.
AB  - BACKGROUND: Correct diagnosis of genuine IgE-mediated opiate allergy poses a
      significant challenge, mainly because of uncertainties associated with opiate
      skin testing and the unavailability of drug-specific IgE (sIgE) assays. Recently,
      it has been suggested that sIgE to poppy seed extract and morphine would be
      reliable in the diagnosis of opiate allergy. However, given the high prevalence
      of sIgE antibodies to these compounds in an allergic population, the predictive
      value of these tests leaves significant doubts. OBJECTIVE: This study aims at
      verifying the predictive value of positive poppy seed and morphine sIgE assays
      results. METHODS: A total of 22 individuals with a positive sIgE to poppy seed or
      morphine were selected. All had controlled drug challenges with increasing doses
      of morphine and/or codeine. Of these, 18 patients had an additional basophil
      activation test (BAT) with morphine and codeine. RESULTS: None of the 22 patients
      demonstrated objective or subjective symptoms on provocation with morphine and/or
      codeine. Regarding BAT with morphine and codeine, expression of CD63 on basophils
      from 14 opiate tolerant individuals remained comparable to spontaneous expression
      by resting cells. The remaining 4 patients were classified as nonresponders.
      CONCLUSION: Positive sIgE results to poppy seed and morphine are not per se
      predictive for genuine opiate allergy and should not be used in isolation to
      diagnose morphine or codeine allergy. To avoid overdiagnosis, for the time being,
      we propose to supplement serological diagnosis with an oral provocation test.
      Whether BAT might help to discriminate between clinical reactivity and
      sensitization remains to be confirmed in larger collaborative studies.

PMID- 25956314
TI  - Is the use of epinephrine a good marker of severity of allergic reactions during
      oral food challenges?

PMID- 25956315
TI  - Frequent episodes of adult soybean allergy during and following the pollen
      season.

PMID- 25956316
TI  - Moxifloxacin hypersensitivity: Uselessness of skin testing.

PMID- 25956317
TI  - 6-year-old boy with recurrent sinopulmonary infections and lymphadenopathy.

PMID- 25956318
TI  - Eosinophilic granulomatosis with polyangiitis (Churg-Strauss vasculitis).

PMID- 25956319
TI  - Transcript variability and physiological correlates in the fathead minnow ovary:
      Implications for sample size, and experimental power.
AB  - Fundamental studies characterizing transcript variability in teleost tissues are
      needed if molecular endpoints are to be useful for regulatory ecotoxicology. The
      objectives of this study were to (1) measure transcript variability of
      steroidogenic enzymes and steroid receptors in the fathead minnow (FHM;
      Pimephales promelas) ovary to better determine normal variability and the sample
      sizes needed to detect specific effect sizes and to (2) determine how expression
      patterns related to higher level endpoints used in some regulatory ecotoxicology
      programs (e.g. relative gonad size). Estrogen receptor 2b (esr2b) and 5alpha
      reductase a3 (srd5a3) showed high variability in the ovary (CV>1.0) while
      progesterone receptor (pgr), androgen receptor (ar), and esr2a showed
      comparatively low variability (CV=~0.5--0.7). Using these estimates, a power
      analysis revealed that sample sizes for real-time PCR experiments would need to
      be>20 to detect a 2-fold change for 7 of the transcripts examined; thus many
      molecular studies conducted in the fish ovary may have insufficient power to
      detect smaller effects. Two transcripts were correlated to steroid production in
      the ovary; cyp19a1 levels were positively correlated to in vitro E2 production,
      while ar levels were negatively correlated to in vitro T production. Thus, these
      transcripts may be informative molecular surrogates for ovarian steroid
      production. No transcript investigated showed any correlation to GSI, condition,
      or body weight/length. Molecular approaches in fish are increasingly used to
      assess biological impacts of chemical stressors; however additional studies are
      required that determine how molecular variability relates to higher level
      biological endpoints. 

PMID- 25956321
TI  - Monocytic elastase-mediated apolipoprotein-E degradation: Potential involvement
      of microglial elastase-like proteases in apolipoprotein-E proteolysis in brains
      with Alzheimers disease.
AB  - Impaired clearance of soluble Abeta (amyloid-beta) promotes Abeta aggregation in
      brains with Alzheimer's disease (AD), while apolipoprotein-E (ApoE) in microglia
      mediates Abeta clearance. We studied the protease responsible for ApoE(4)
      degradation in human peripheral monocyte extracts, which are from the same
      lineage as microglia. We detected the hydrolytic activity for ApoE(4) in high
      salt extracts with 2 M NaCl and found that the activity was inhibited by a serine
      protease inhibitor and an elastase-specific inhibitor, but not by other protease
      inhibitors. The extracts exhibited higher activity for the elastase substrate,
      and we followed the activity with ion-exchange and gel-filtration chromatography.
      Through silver staining, we partially purified a protein of 28 kDa, which was
      clarified as elastase by liquid chromatography-tandem mass spectrometry. These
      observations suggest that elastase is the key protease for ApoE(4) degradation.
      We also detected ApoE(4) hydrolytic activity in high-salt extracts in mouse
      microglial (BV-2) cell lysates, and showed that the ApoE(4) fragments by the BV-2
      extracts differed from the fragments by the monocyte extracts. Though the ApoE(4)
      degradation by the extracts was not inhibited with elastase-specific inhibitors,
      it was inhibited by an elastase-specific monoclonal antibody, suggesting that
      elastase-like proteases in microglia differ from those of monocytes.
      Immunohistochemistry revealed that both elastase and ApoE were expressed in the
      senile plaques of brains with AD. In vitro studies also disclosed the
      localization of elastase in the microglial cell line, BV-2. Our results suggest
      that elastase-like proteases in the microglial cells surrounding Abeta plaques
      are responsible for ApoE degradation in the brain.

PMID- 25956320
TI  - Critical residues involved in Toll-like receptor 4 activation by cationic lipid
      nanocarriers are not located at the lipopolysaccharide-binding interface.
AB  - DiC14-amidine is a cationic lipid that was originally designed as a lipid
      nanocarrier for nucleic acid transport, and turned out to be a Toll-like receptor
      4 (TLR4) agonist as well. We found that while E. coli lipopolysaccharide (LPS) is
      a TLR4 agonist in all species, diC14-amidine nanoliposomes are full agonists for
      human, mouse and cat receptors but weak horse agonists. Taking advantage of this
      unusual species specificity, we used chimeric constructs based on the human and
      horse sequences and identified two regions in the human TLR4 that modulate the
      agonist activity of diC14-amidine. Interestingly, these regions lie outside the
      known LPS-binding domain. Competition experiments also support our hypothesis
      that diC14-amidine interacts primarily with TLR4 hydrophobic crevices located at
      the edges of the TLR4/TLR4* dimerization interface. We have characterized
      potential binding modes using molecular docking analysis and suggest that diC14
      amidine nanoliposomes activate TLR4 by facilitating its dimerization in a process
      that is myeloid differentiation 2 (MD-2)-dependent and cluster of differentiation
      14 (CD14)-independent. Our data suggest that TLR4 may be activated through
      binding at different anchoring points, expanding the repertoire of TLR4 ligands
      to non-MD-2-binding lipids.

PMID- 25956322
TI  - Unraveling the mechanism responsible for the contrasting tolerance of
      Synechocystis and Synechococcus to Cr(VI): Enzymatic and non-enzymatic
      antioxidants.
AB  - Two unicellular cyanobacteria, Synechocystis and Synechococcus, showed
      contrasting tolerance to Cr(VI); with Synechococcus being 12-fold more tolerant
      than Synechocystis to potassium dichromate. The mechanism responsible for this
      differential sensitivity to Cr(VI) was explored in this study. Total content of
      photosynthetic pigments as well as photosynthetic activity decreased at lower
      concentration of Cr(VI) in Synechocystis as compared to Synechococcus.
      Experiments with (51)Cr showed Cr to accumulate intracellularly in both the
      cyanobacteria. At lower concentrations, Cr(VI) caused excessive ROS generation in
      Synechocystis as compared to that observed in Synechococcus. Intrinsic levels of
      enzymatic antioxidants, i.e., superoxide dismutase, catalase and 2-Cys
      peroxiredoxin were considerably higher in Synechococcus than Synechocystis.
      Content of total thiols (both protein as well as non-protein) and reduced
      glutathione (GSH) was also higher in Synechococcus as compared to Synechocystis.
      This correlated well with higher content of carbonylated proteins observed in
      Synechocystis than Synechococcus. Additionally, in contrast to Synechocystis,
      Synechococcus exhibited better tolerance to other oxidative stresses like high
      intensity light and H2O2. The data indicate that the disparity in the ability to
      detoxify ROS could be the primary mechanism responsible for the differential
      tolerance of these cyanobacteria to Cr(VI). 

PMID- 25956323
TI  - Estrogenicity and intersex in juvenile rainbow trout (Oncorhynchus mykiss)
      exposed to Pine/Eucalyptus pulp and paper production effluent in Chile.
AB  - Pulp and paper mill effluents (PPMEs) have been shown to increase gonad size,
      cause early maturation, and disrupt hormone functions in native and non-native
      Chilean fish. In this study, we assessed reproductive (plasma vitellogenin; VTG,
      gonad development) and metabolic (ethoxyresorufin-O-deethylase activity; EROD)
      end points, relative liver size (LSI) and condition factor (K) of juvenile female
      and male rainbow trout exposed to effluents. Unlike previous studies, which have
      focus either on the specific effects of effluent on fish in laboratory exposures
      or biotic population statuses downstream of discharge sites, we simultaneously
      assessed the impacts of PPMES on trout using two approaches: (1) laboratory
      exposures of tertiary treated PPME produced from processing Eucalyptus globulus
      or Pinus radiata; and (2) in situ bioassay downstream of the combined discharge
      of the same pulp mill. Despite an increase in the average gonadosomatic index
      (GSI) in exposed fish, no statistical differences in gonad size between exposed
      and unexposed individuals was detected. However, both female and male fish
      exposed to effluents showed significantly higher concentrations of plasma VTG, so
      more in fish exposed to Eucalyptus-based effluent when compared to Pinus PPME. In
      addition, male fish showed intersex characteristics in all exposure assays
      (Eucaliptus and Pinus) and, despite the low concentration of effluent in the
      river (<1% [v/v]), similar responses were observed in the caged fish. Finally,
      EROD activity was induced in both in situ exposures and laboratory assays at the
      higher PPME concentration (60-85% PPME). This study confirms estrogenic effects
      in Chilean fish exposed to PPME and the necessity for biological effects
      monitoring in addition to the assessment of physical-chemical endpoints as
      required in current government regulations. 

PMID- 25956325
TI  - Molecular structure, spectroscopic characterization of (S)-2-Oxopyrrolidin-1-yl
      Butanamide and ab initio, DFT based quantum chemical calculations.
AB  - The experimental and theoretical spectra of (S)-2-Oxopyrrolidin-1-yl Butanamide
      (S2OPB) were studied. FT-IR and FT-Raman spectra of S2OPB in the solid phase were
      recorded and analyzed in the range 4000-450 and 5000-50 cm(-1) respectively. The
      structural and spectroscopic analyses of S2OPB were calculated using ab initio
      Hartree Fock (HF) and density functional theory calculations (B3PW91, B3LYP) with
      6-31G(d,p) basis set. A complete vibrational interpretation has been made on the
      basis of the calculated Potential Energy Distribution (PED). The HF, B3LYP and
      B3PW91 methods based NMR calculation has been used to assign the (1)H NMR and
      (13)C NMR chemical shift of S2OPB. Comparative study on UV-Vis spectral analysis
      between the experimental and theoretical (B3PW91, B3LYP) methods and the global
      chemical parameters and local descriptor of reactivity through the Fukui function
      were performed. Finally the thermodynamic properties of S2OPB were calculated at
      different temperatures and the corresponding relations between the properties and
      temperature were also studied.

PMID- 25956326
TI  - Investigation of Fluorescence Resonance Energy Transfer between Fluorescein and
      Rhodamine 6G.
AB  - Fluorescence Resonance Energy Transfer between two organic dyes Fluorescein and
      Rhodamine 6G was investigated in aqueous solution in presence and absence of
      synthetic clay laponite. Spectroscopic studies suggest that both the dyes were
      present mainly as monomer in solution. Fluorescence Resonance Energy Transfer
      occurred from Fluorescein to Rhodamine 6G in solutions. Energy transfer
      efficiency increases in presence of laponite and the maximum efficiency was
      72.00% in aqueous laponite dispersion. Energy transfer efficiency was found to be
      pH sensitive. It has been demonstrated that with proper calibration it is
      possible to use the present system under investigation to sense pH over a wide
      range from 1.5 to 8.0. 

PMID- 25956327
TI  - Study on DNA binding behavior and light switch effect of new coumarin-derived
      Ru(II) complexes.
AB  - A new ligand mhcip (mhcip=2-(4-methyl-7-hydroxyl-8-coumarinyl)imidazo[4,5-f]
      [1,10]phenanthroline) and its ruthenium complexes, [Ru(L)2mhcip](2+) (L=bpy (2,2'
      bipyridine), phen (1,10-phenanthroline)), have been synthesized and
      characterized. The introduction of coumarin ring may play an important role in
      the strong fluorescence of the complexes. Intercalative binding mode between both
      complexes and CT-DNA was determined by UV-visible spectroscopy, fluorescence
      spectroscopy and viscosity measurements. The two complexes show efficient DNA
      photocleavage under irradiation at 365 nm. The cycling of light switch off and on
      has been achieved for both complexes through the introduction of Cu(2+) and EDTA
      in the absence or presence of DNA.

PMID- 25956328
TI  - Impact of the different electron-releasing subunits on the dye-sensitized solar
      cell performance of new triphenylamine-benzimidazole based molecules.
AB  - New triphenylamine-benzimidazole type small molecules with different electron
      releasing groups were designed and synthesized to investigate their photovoltaic
      performances in dye sensitized solar cells (DSSCs). Their good visible
      absorptions covering the 400-535 nm in addition to suitable lowest unoccupied
      molecular orbital (LUMO) energy levels between -3.03 and -3.11 eV make good
      candidates them for DSSC devices. Fluorescence quenching studies of the dyes with
      pristine titania support the good electron injection to conduction band of TiO2.
      Time resolved measurements of the dyes in solutions indicate the occurence of
      charge generation during the excited state. One of the used dyes in DSSC devices,
      TPA5a, carrying a methoxy group in triphenylamine part of the structure, gave
      much higher power conversion efficiency (PCE) value of 4.31% as compared to the
      other derivatives. Device fabricated from TPA5a dye gives good external quantum
      efficiency (EQE) value above 70% at 460 nm. Also, electron impedance spectroscopy
      (EIS) analysis of the devices gives a good explanation of the understanding of
      the cell performances.

PMID- 25956324
TI  - Cell death disguised: The mitochondrial permeability transition pore as the c
      subunit of the F(1)F(O) ATP synthase.
AB  - Ion transport across the mitochondrial inner and outer membranes is central to
      mitochondrial function, including regulation of oxidative phosphorylation and
      cell death. Although essential for ATP production by mitochondria, recent
      findings have confirmed that the c-subunit of the ATP synthase also houses a
      large conductance uncoupling channel, the mitochondrial permeability transition
      pore (mPTP), the persistent opening of which produces osmotic dysregulation of
      the inner mitochondrial membrane and cell death. This review will discuss recent
      advances in understanding the molecular components of mPTP, its regulatory
      mechanisms and how these contribute directly to its physiological as well as
      pathological roles. 

PMID- 25956329
TI  - Effective intercalation of sodium dodecylsulfate (SDS) into hydrocalumite:
      Mechanism discussion via near-infrared and mid-infrared investigations.
AB  - The intercalation of an anionic surfactant, sodium dodecylsulfate (SDS), into
      hydrocalumite (CaAl-LDH-Cl) was investigated in this study. To understand the
      intercalation behavior, X-ray diffraction (XRD), mid-infrared spectroscopy (MIR),
      near-infrared spectroscopy (NIR) and scanning electron microscopy (SEM) were
      undertaken. The near-infrared spectra indicated a special spectral range from
      6000 to 5600 cm(-1)and prominent bands of CaAl-LDH-Cl intercalated with SDS
      around 8388 cm(-1). This band was assigned to the second overtone of the first
      fundamental of CH stretching vibrations of SDS, and it could be used to
      determinate the result of CaAl-LDH-Cl modified by SDS. Moreover, the results
      revealed that different adsorption behaviors were observed at different (high and
      low) concentrations of SDS. When the SDS concentration was around 0.2 mol L(-1),
      anion exchange intercalation occurred and the interlayer distance expanded to
      about 3.25 nm. When SDS concentration was 0.005 mol L(-1), the surface adsorption
      of DS(-) was the major anion exchange event.

PMID- 25956330
TI  - Raman and infrared spectroscopic study of turquoise minerals.
AB  - Raman and infrared spectra of three well-defined turquoise samples,
      CuAl6(PO4)4(OH)8.4H2O, from Lavender Pit, Bisbee, Cochise county, Arizona;
      Kouroudaiko mine, Faleme river, Senegal and Lynch Station, Virginia were studied,
      interpreted and compared. Observed Raman and infrared bands were assigned to the
      stretching and bending vibrations of phosphate tetrahedra, water molecules and
      hydroxyl ions. Approximate O-H?O hydrogen bond lengths were inferred from the
      Raman and infrared spectra. No Raman and infrared bands attributable to the
      stretching and bending vibrations of (PO3OH)(2-) units were observed. 

PMID- 25956331
TI  - Structural, thermal and optical properties of KTi(0.92)La(0.08)OPO4 and
      KTi(0.94)Nd(0.06)OPO4.
AB  - KTi0.92La0.08OPO4 (KTP:La) and KTi0.94Nd0.06OPO4 (KTP:Nd) single crystals are
      grown using high temperature top seeded flux growth technique. The strain derived
      from doping is calculated from Williamson-Hall relation. The packing structure
      and lattice parameter of the grown crystals are analyzed using single crystal X
      ray diffraction. The bonding, distortion and change in inter-atomic distances by
      strain effects of doping are assessed by Raman spectroscopy. Thermal stabilities
      of grown crystals are evaluated by specific heat capacity measurement. Pronounced
      high specific heat capacity is recorded as 1.16 J/gK at 498 K for KTP:Nd. Second
      harmonic generation intensities are measured for KTP:Nd and KTP:La single
      crystal.

PMID- 25956332
TI  - Surface enhanced Raman scattering of new acridine based fluorophore adsorbed on
      silver electrode.
AB  - 4,5-Bis(N,N-di(2-hydroxyethyl)iminomethyl)acridine (BHIA) is a new acridine based
      fluoroionophore and a highly-selective sensor for cadmium ion. The direct
      interaction of the aromatic nitrogen atom with a surface is impossible since
      there are bulky substituents in the 4,5-positions of the acridine fragment.
      Nevertheless BHIA molecule shows a reliable SERS spectrum while adsorbed on a
      silver electrode. The analysis of SERS spectra pH dependence reveals that BHIA
      species adsorbed on a surface can exist in both non-protonated and protonated
      forms. The adsorption of BHIA from alkaline solution is accompanied by
      carbonaceous species formation at the surface. The intensity of such "carbon
      bands" turned out to be related with the supporting electrolyte (KCl)
      concentration. Upon lowering the electrode potential the SERS spectra of BHIA do
      not undergo changes but the intensity of bands decreases. This indicates that the
      adsorption mechanism on the silver surface is realized via aromatic system of
      acridine fragment. In case of such an adsorption mechanism the chelate fragment
      of the BHIA molecule is capable of interaction with the solution components.
      Addition of Cd(2+) ions to a system containing BHIA adsorbed on a silver
      electrode in equilibrium with the solution leads to the formation of BHIA/Cd(2+)
      complex which desorption causes the loss of SERS signal. 

PMID- 25956333
TI  - Higher vitamin D intake during pregnancy is associated with reduced risk of
      dental caries in young Japanese children.
AB  - PURPOSE: The intrauterine environment, including maternal nutrition status, may
      affect the development, formation, and mineralization of children's teeth. We
      assessed the relationship between self-reported maternal dietary vitamin D intake
      during pregnancy and the risk of dental caries among young Japanese children.
      METHODS: This study is based on a prospective analysis of 1210 Japanese mother
      child pairs. Information on maternal intake during pregnancy was collected using
      a validated diet history questionnaire. Data on oral examination at 36-46 months
      of age were obtained from the mothers, who transcribed the information from their
      maternal and child health handbooks to our self-administered questionnaire.
      Children were classified as having dental caries if one or more primary teeth had
      decayed or had been filled. RESULTS: Compared with the lowest quartile of
      maternal vitamin D intake during pregnancy, adjusted odds ratios (95% confidence
      intervals) for quartiles 2, 3, and 4 were 1.06 (0.72-1.56), 0.53 (0.34-0.81), and
      0.67 (0.44-1.02), respectively (P for trend = .01). When maternal vitamin D
      intake was treated as a continuous variable, the adjusted odds ratio (95%
      confidence interval) was 0.94 (0.89-0.995). CONCLUSIONS: Higher maternal vitamin
      D intake during pregnancy may be associated with a lower risk of dental caries in
      children.

PMID- 25956334
TI  - Single particle tomography in EMAN2.
AB  - Single particle tomography (SPT or subtomogram averaging) offers a powerful
      alternative to traditional 2-D single particle reconstruction for studying
      conformationally or compositionally heterogeneous macromolecules. It can also
      provide direct observation (without labeling or staining) of complexes inside
      cells at nanometer resolution. The development of computational methods and tools
      for SPT remains an area of active research. Here we present the EMAN2.1 SPT
      toolbox, which offers a full SPT processing pipeline, from particle picking to
      post-alignment analysis of subtomogram averages, automating most steps. Different
      algorithm combinations can be applied at each step, providing versatility and
      allowing for procedural cross-testing and specimen-specific strategies. Alignment
      methods include all-vs-all, binary tree, iterative single-model refinement,
      multiple-model refinement, and self-symmetry alignment. An efficient angular
      search, Graphic Processing Unit (GPU) acceleration and both threaded and
      distributed parallelism are provided to speed up processing. Finally, automated
      simulations, per particle reconstruction of subtiltseries, and per-particle
      Contrast Transfer Function (CTF) correction have been implemented. Processing
      examples using both real and simulated data are shown for several structures. 

PMID- 25956335
TI  - Helium ion microscopy and ultra-high-resolution scanning electron microscopy
      analysis of membrane-extracted cells reveals novel characteristics of the
      cytoskeleton of Giardia intestinalis.
AB  - Giardia intestinalis presents a complex microtubular cytoskeleton formed by
      specialized structures, such as the adhesive disk, four pairs of flagella, the
      funis and the median body. The ultrastructural organization of the Giardia
      cytoskeleton has been analyzed using different microscopic techniques, including
      high-resolution scanning electron microscopy. Recent advances in scanning
      microscopy technology have opened a new venue for the characterization of
      cellular structures and include scanning probe microscopy techniques such as
      ultra-high-resolution scanning electron microscopy (UHRSEM) and helium ion
      microscopy (HIM). Here, we studied the organization of the cytoskeleton of G.
      intestinalis trophozoites using UHRSEM and HIM in membrane-extracted cells. The
      results revealed a number of new cytoskeletal elements associated with the
      lateral crest and the dorsal surface of the parasite. The fine structure of the
      banded collar was also observed. The marginal plates were seen linked to a
      network of filaments, which were continuous with filaments parallel to the main
      cell axis. Cytoplasmic filaments that supported the internal structures were seen
      by the first time. Using anti-actin antibody, we observed a labeling in these
      filamentous structures. Taken together, these data revealed new surface
      characteristics of the cytoskeleton of G. intestinalis and may contribute to an
      improved understanding of the structural organization of trophozoites. 

PMID- 25956336
TI  - Neonates and isomerism: Are the rules different?

PMID- 25956337
TI  - Total arch for type A dissection?

PMID- 25956338
TI  - Greater asymmetric wall shear stress in Sievers' type 1/LR compared with 0/LAT
      bicuspid aortic valves after valve-sparing aortic root replacement.
AB  - OBJECTIVE: To evaluate the role of commissure orientation on downstream blood
      flow patterns and ascending aortic wall shear stress (WSS) in patients with
      bicuspid aortic valves (BAV) after valve-sparing aortic root replacement (V
      SARR). METHODS: Nineteen BAV patients after V-SARR (9 Sievers' type 1/LR [type 1
      valve with fusion of the left and right cusps] and 10 Sievers' type 0/LAT
      ["naturally perfect"; type 0 valve without the presence of a raphe, and with the
      2 commissures oriented right-anterior-to-left-posterior]) were imaged using time
      resolved 3-D phase contrast magnetic resonance imaging. A control group of 5
      unoperated tricuspid aortic valve patients were used for comparison purposes.
      Wall shear stress and eccentricity of flow normalized to aortic diameter were
      measured in planes placed perpendicular to the axis of the ascending aorta at the
      level of the sinotubular junction (proximal ascending), main pulmonary artery
      (mid-ascending), and origin of the brachiocephalic (distal ascending). RESULTS:
      The ratio of WSS along the outer curvature to that along the inner curvature was
      greater in Sievers' type 1/LR patients compared with Sievers' type 0/LAT patients
      in the proximal (3.8 +/- 1.6 vs 2.1 +/- 0.9, P = .009) and mid- ascending aorta
      (4.5 +/- 2.4 vs 2.4 +/- 1.3, P = .027). Relative to control normal tricuspid
      patients, Sievers' type 1/LR BAV patients had a higher WSS ratio in the mid
      ascending aorta (4.5 +/- 2.4 vs 1.2 +/- 1.2, P = .007). Conversely, WSS in
      Sievers' type 0/LAT patients was not different than in normal tricuspid patients.
      CONCLUSIONS: After V-SARR, BAV cusp morphology has a major impact on the pattern
      of blood flow and WSS in the ascending aorta.

PMID- 25956339
TI  - MicroRNAs: Panacea or Pandora's box?

PMID- 25956340
TI  - The effect of coexisting squamous cell lesions on prognosis in patients with
      cervical adenocarcinoma in situ.
AB  - OBJECTIVE: The aim of this study was to assess the relative incidences of
      cervical adenocarcinoma in situ (AIS) and squamous cell carcinoma in situ (sCIS)
      and to determine the effect of coexisting squamous cell lesions on prognosis in
      patients with cervical AIS. STUDY DESIGN: We performed a retrospective review of
      patients diagnosed with AIS or sCIS who underwent cervical conization at a
      University hospital between 2000 and 2011. RESULTS: A total of 1184 patients with
      cervical carcinoma in situ were included. The ratio of sCIS to AIS was 16:1.
      Among 71 patients with AIS, AIS with coexisting squamous cell lesions and AIS
      alone were detected in 41 patients (58%) and 30 patients (42%), respectively.
      During the median follow-up of 57.1 months, 5 episodes of AIS recurrences and one
      episode of invasive recurrence occurred. The recurrence rate was significantly
      higher in patients with AIS alone than in patients with AIS and coexisting
      squamous cell lesions (17% versus 2%; P=0.043). CONCLUSION: These results suggest
      that patients with cervical AIS and coexisting squamous cell lesions have a more
      favorable prognosis than patients with AIS alone.

PMID- 25956341
TI  - Efficacy and tolerability of early administration of valnemulin hydrochloride
      premix on epizootic rabbit enteropathy.
AB  - A blinded, randomised, placebo-controlled clinical trial was conducted to
      evaluate the efficacy and safety of valnemulin hydrochloride premix during an
      outbreak of epizootic rabbit enteropathy (ERE) when administered in feed for 21
      consecutive days after confirmation of the first ERE case. Administration of
      valnemulin at 20 and 35 parts per million (ppm) significantly reduced mortality
      by 11% and 7.6%, respectively, when compared with the non-medicated control group
      (23% mortality). Non-ERE related adverse events, including dysbacteriosis,
      enterotoxaemia and pneumonia, occurred in all groups at similar frequencies
      (untreated: 1.8%; 20 ppm valnemulin: 2.8%; 35 ppm valnemulin: 1.3%).
      Administration of valnemulin did not affect feed consumption or body weight gain;
      treated rabbits had sustained weight gain and feed conversion rates (FCRs).
      However, from days 7 to 21 of the outbreak, untreated rabbits had significantly
      lower daily weight gains and higher FCRs than medicated rabbits, suggesting a
      protective effect of valnemulin during the peak of the disease. Untreated rabbits
      exhibited compensatory growth from days 21 to 28, when the last observation was
      made. FCRs for the entire study were similar among all three groups. Impaction
      and diarrhoea were more frequent in untreated animals, with a poor prognosis,
      while tympanism was more common in valnemulin-treated rabbits that survived. In
      conclusion, early administration of valnemulin hydrochloride premix at 20 or 35
      ppm is efficacious and safe for the treatment of naturally occurring ERE. 

PMID- 25956342
TI  - The effects of surgery-induced immunosuppression and angiogenesis on tumour
      growth.
AB  - Surgical removal of primary tumours can help in the treatment of cancer but
      carries the risk of triggering the proliferation of dormant micrometastases. Many
      experimental and clinical studies have demonstrated that anti-angiogenic
      mechanisms and immune surveillance are essential to inhibit metastatic tumour
      cells from growing. As surgical stress often induces a reduction in anti
      angiogenic factors in parallel with increases in angiogenic factors and
      suppression of immune surveillance during the post-operative period, new
      strategies for peri-operative immunostimulation and chemotherapy are required.
      This review summarises the factors and proposed mechanisms underlying the effects
      of surgery on immunosuppression and angiogenesis. 

PMID- 25956343
TI  - Expression and clinical relevance of paired box protein 7 and sex determining
      region Y-box 2 in canine corticotroph pituitary adenomas.
AB  - Pituitary-dependent hypercortisolism is a common endocrinopathy in dogs, caused
      by an adrenocorticotrophic hormone secreting pituitary tumour of the anterior or
      intermediate lobe. The prognosis of intermediate lobe adenomas is worse than that
      of anterior lobe adenomas, indicating the possible usefulness of melanotropic
      markers as prognosticators. Another possible origin of pituitary adenomas is
      found in cancer stem cells. The aim of the present study was to investigate the
      expression of melanotroph specific transcription factor paired box protein 7
      (Pax7) and stem cell marker and reprogramming factor sex determining region Y-box
      2 (Sox2) and to relate their expression to clinical parameters. The mean +/- SD
      of labelling index (LI) for Pax7 was 8.6% +/- 21.7% in the adenomas; 1/6 controls
      had positive staining (LI, 15.2%). For Sox2, the LI in the adenomas was 16.9% +/-
      15.2% and 19.5% +/- 11.6% in the controls. Pax7 expression was significantly
      higher in enlarged pituitaries, compared to non-enlarged pituitaries (P = 0.05),
      but Pax7 or Sox2 immunopositivity did not correlate to other clinical parameters
      such as histological diagnosis, survival time or disease-free interval. Gene
      expression of Pax7 target genes, such as proconvertase 2 (PC2), pro
      opiomelanocortin (POMC), and dopamine D2 receptor (DRD2), was significantly lower
      in the adenoma samples compared to normal tissue, indicating that Pax7 signalling
      was not activated in adenomas. It was suggested that Pax7 and Sox2 remain
      interesting targets for molecular investigations into their role in pituitary
      tumorigenesis, but were unsuitable as clinical prognosticators in dogs. 

PMID- 25956344
TI  - Molecular and immunohistochemical studies do not support a role for
      papillomaviruses in canine oral squamous cell carcinoma development.
AB  - Oral squamous cell carcinomas (OSCCs) are common neoplasms of dogs and are of
      unknown cause. Whereas papillomaviruses (PVs) are an established cause of human
      OSCCs, few studies have investigated canine OSCCs for a PV aetiology. In humans,
      a PV aetiology can be determined by detecting PV DNA and PV-induced increased
      p16(CDKN2A) protein (p16) within the OSCC. In this study, PCR, using four
      different primer sets and p16 immunohistochemistry, was used to evaluate 28
      canine OSCCs for a possible PV aetiology. None of the primers amplified PV DNA
      from any of the OSCCs although four neoplasms contained intense p16
      immunostaining. Intense p16 immunostaining would indicate a PV aetiology in a
      human OSCC but the absence of PV DNA suggests that the increase in p16 was not
      due to PV infection. Overall the results indicated that PVs are not a significant
      cause of canine OSCCs. 

PMID- 25956345
TI  - Clinical use of dipeptidyl peptidase-4 and sodium-glucose cotransporter 2
      inhibitors in combination therapy for type 2 diabetes mellitus.
AB  - OBJECTIVE: To review the efficacy, safety, and tolerability of combination
      treatment regimens including a dipeptidyl peptidase-4 (DPP-4) inhibitor and/or
      sodium-glucose cotransporter 2 (SGLT2) inhibitor for type 2 diabetes mellitus
      (T2DM). METHODS: Clinical trials of combination therapies including a DPP-4
      and/or SGLT2 inhibitor were identified through a PubMed database search. To be
      included, studies had to have a primary end point of change from baseline to >=24
      weeks in glycated hemoglobin, include >=1 other oral antidiabetic drug (OAD), and
      have randomized more than 200 patients. Results were limited to medications
      approved by the US Food and Drug Administration at the time of the search (March
      2015). RESULTS: A total of 1534 articles for the DPP-4 inhibitor class and 434
      articles for the SGLT2 inhibitor class were retrieved from PubMed. Of these, 33
      articles from the DPP-4 inhibitor class and 24 articles from the SGLT2 inhibitor
      class were included for review. In each study, the addition of a DPP-4 or SGLT2
      inhibitor as a second or third agent resulted in improved glycemic control versus
      comparator arms. Reductions in weight or lack of weight gain were consistently
      observed, as were low rates of hypoglycemic events, particularly when the
      combination regimen also included metformin. Overall, the pattern of adverse
      events observed in combination treatment groups was consistent with the known
      effects of the individual agents. CONCLUSION: Combination treatment with a DPP-4
      and/or SGLT2 inhibitor is an efficacious option for patients with T2DM starting
      pharmacological therapy, or for patients who have received treatment but require
      additional glycemic control. Study findings indicate that the underlying
      mechanisms of action of DPP-4 inhibitors and SGLT2 inhibitors complement a
      variety of OADs.

PMID- 25956346
TI  - Assessing the performance characteristics and clinical forces in simulated shape
      memory bone staple surgical procedure: The significance of SMA material model.
AB  - This work is focused on the detailed computer simulation of the key stages
      involved in a shape memory alloy (SMA) osteosynthesis bone stapling procedure. To
      this end, a recently developed three-dimensional constitutive SMA material model
      was characterized from test data of three simple uniaxial-isothermal-tension
      experiments for powder metallurgically processed nickel-rich NiTi (PM/NiTi-P)
      material. The calibrated model was subsequently used under the complex,
      thermomechanical loading conditions involved in the surgical procedure using the
      body-temperature-activated PM/NiTi-P bone staple. Our aim here is to assess the
      immediate and post-surgical performance characteristics of the stapling operation
      using the material model. From this study: (1) it was found that adequate
      compressive forces were developed by the PM/NiTi-P bone staple, with the tendency
      of this force to even increase under sustained thermal loading due to the
      intrinsic "inverse relaxation phenomena" in the SMA material, (2) the simulation
      results correlated well with those from experimental measurements, (3) the body
      temperature-activated PM/NiTi-P staple was proved to be clinically viable,
      providing a stable clamping force needed for speedy coaptation of the fractured
      bones, and (4) these realistic assessments crucially depend on the use of
      suitable and comprehensive SMA material models. 

PMID- 25956347
TI  - Novel diagnostic tools and solutions for multiple sclerosis treatment: a patent
      review (2009 - 2014).
AB  - INTRODUCTION: With > 2 million people affected by multiple sclerosis (MS)
      worldwide, the elucidation of its etiopathogenesis is of highest interest.
      Ongoing research in medicine, molecular biology, chemistry and physics aims to
      improve the life of MS patients by increasing efficacy and decreasing adverse
      side effects of presently available drugs. A precise diagnosis of this complex
      disease, which can take different courses, is fundamental to finding an efficient
      treatment strategy. AREAS COVERED: We present a summary of diagnostic and
      therapeutic patents granted between 2009 and 2014. Diagnostic inventions use both
      genetic and proteomic approaches or measure cerebral venous hemodynamics.
      Instead, new treatments rely on small molecules and/or the active manipulation of
      proteins that are involved in the pathogenesis of MS. EXPERT OPINION: There are
      some promising approaches among recently published patents. In particular,
      genetic profiling for diagnosis, combination of novel drugs with FDA-approved
      drugs to reduce side effects, and the personalisation of MS treatments according
      to a more defined diagnosis are considered as important. In the light of the
      latest developments, we discuss the complex picture of MS, which we assume to be
      different events connected by a causal chain consisting of circulatory
      abnormalities, altered redox processes in CNS immune cells, oligodendropathy,
      inflammation and finally autoimmunity.

PMID- 25956348
TI  - Virus safety of islet cell transplantation from transgenic pigs to marmosets.
AB  - Transplantation of pig islet cells for the treatment of diabetes may be a more
      effective approach compared with the application of insulin. However, before
      introduction into the clinic, efficacy and safety of this treatment have to be
      shown. Non-human primate models may be used for this, despite the fact that they
      are characterised by several limitations. Here we investigate the prevalence of
      porcine endogenous retroviruses (PERVs), which are present in the genome of all
      pigs and which may infect human cells, as well as of porcine herpes viruses in
      donor pigs and their potential transmission to non-human primate recipients.
      Despite the fact that all three subtypes of PERV were present in all and porcine
      cytomegalovirus (PCMV) was found in some of the pigs, neither PERVs nor PCMV were
      found in the recipient animals under the experimental conditions applied. Porcine
      lymphotropic herpes viruses (PLHV) were not found in the donor pigs, hepatitis E
      virus (HEV) was not found in the recipients. 

PMID- 25956349
TI  - [Morbidity of pelvic lymphadenectomy and para-aortic lymphadenectomy in
      endometrial cancer].
AB  - The aim of this study was to evaluate the complication rate of pelvic and para
      aortic lymphadenectomy in the management of endometrial cancer following the
      changes to the recommendations of INCa 2010. This is a retrospective study of 208
      patients operated for endometrial cancer between July 2010 and March 2014 in two
      referral centers. Eighty lymphadenectomy were performed, 65 with hysterectomy and
      bilateral annexectomy and 18 lymphadenectomy were performed for restaging.
      Complications assessment is based on the Dindo Clavien classification. We report
      17 severe complications (grade 3a and over) (P<0.001), including 14 among
      patients receiving lymphadenectomy. Morbidity increases with the number of
      lymphnodes removed and their positivity (P<0.001). The para-aortic
      lymphadenectomy is primarily responsible for complications (P <0.001). We
      describe 7 lower limbs lymphedema, 12 nerve injuries, 8 ileus, 5 venous or
      arterial thromboembolism, 17 blood transfusions, 13 lymphoceles including 9
      infected. The rate of intraoperative complications on a first lymphadenectomy is
      8% while it reached 22% for restaging. Restaging is significantly more at risk of
      serious complications (P=0.03) with two deaths. Twenty-four chronic disorders
      with impaired quality of life (2 without lymphadenectomy) are reported. They are
      present in 50% of restaging (P=0.033 compared to first lymphadenectomy).
      Lymphadenectomy is a source of severe morbidity (17.5%) with 2.5% mortality. The
      benefit of this surgery should probably be discussed again.

PMID- 25956350
TI  - [Impact of radiotherapy on female fertility].
AB  - Radiation therapy may have deleterious effects on female fertility. It can cause
      ovarian dysfunction, uterine damages or disrupt the hypothalamic-pituitary axis.
      These effects occur at varying dose levels usually relatively low compared to the
      prescribed doses. Other co-factors influence the effects of radiation therapy on
      fertility, such as age or therapy with alkylating agents. This review aims to
      make an update on the current state of knowledge about the impact of radiotherapy
      on female fertility. 

PMID- 25956351
TI  - Transplantation of cryopreserved human umbilical cord blood-derived endothelial
      progenitor cells induces recovery of carotid artery injury in nude rats.
AB  - INTRODUCTION: Transplantation of endothelial progenitor cells (EPCs) restores
      endothelial function in patients with endothelial dysfunction and initial
      denudation. The goal of the present study was to determine the effect of
      cryopreserved human umbilical cord blood (UCB)-derived EPC infusion on the repair
      of carotid artery injury in nude rats. METHODS: Mononuclear cells (MNCs) from
      human cryopreserved UCB and peripheral blood (PB) of patients with cardiovascular
      diseases and healthy volunteers were cultured in a conditioned medium. The in
      vitro migration, proliferation, adhesion, and survival capacities, as well as
      paracrine cytokine release of EPCs were investigated. EPC homing, induced
      reendothelialization, and the effect on neointima formation were also assessed in
      vivo. RESULTS: Patient-derived PB EPCs (PPB-EPCs) displayed decreased migration,
      proliferation, adhesion, and survival capabilities as compared to PB-EPCs from
      healthy volunteers (HPB-EPCs) and cryopreserved UCB-EPCs. However, there was no
      difference in the release of vascular endothelial growth factor (VEGF) and
      stromal cell derived factor 1 (SDF-1) between the three groups. Two weeks after
      transplantation, more labeled UCB-EPCs and HPB-EPCs than PPB-EPCs were found by
      cell tracking in the injury zone. Administration of PPB-EPCs, HPB-EPCs, and UCB
      EPCs enhanced reendothelialization and inhibited neointima formation compared to
      the saline control. However, UCB-EPC and HPB-EPC infusion showed a greater
      improvement than PPB-EPCs. CONCLUSIONS: Cryopreserved UCB-MNCs derived EPCs and
      HPB-EPCs show better responses to cytokines and vascular injury than PPB-EPCs.
      Thus, cryopreservation and delivery of cryopreserved autogenous UCB-EPCs or HPB
      EPCs may be a promising vasculoprotective approach for patients with multiple
      cardiovascular risk factors.

PMID- 25956352
TI  - Non-celiac gluten sensitivity and rheumatic diseases.
AB  - Celiac disease is an autoimmune systemic disease having among its clinical
      manifestations frequent symptoms common to rheumatologic diseases such as
      musculoskeletal pain, asthenia, and cognitive fatigue. It is associated with
      other autoimmune diseases like Sjogren disease. It is a well-characterized
      disease with specific diagnostic tests. Non-celiac gluten sensitivity is an
      emerging entity with symptoms similar to celiac disease, but without specific
      diagnostic tests. The concept of non-celiac gluten sensitivity and its diagnostic
      problems are reviewed, and the hypothesis of its association with fibromyalgia,
      spondyloarthritis, and autoimmune conditions is proposed. Clinical observations
      supporting the hypothesis are described, highlighting the benefit of treating non
      celiac gluten sensitivity. 

PMID- 25956353
TI  - Efficacy of Tenofovir-based Rescue Therapy in Lamivudine-resistant Chronic
      Hepatitis B Patients With Failure of Lamivudine and Adefovir Combination.
AB  - PURPOSE: In chronic hepatitis B patients, lamivudine (LAM) and adefovir (ADV)
      combination therapy is commonly used as a rescue therapy for LAM resistance, but
      it often results in incomplete viral suppression. We investigated the antiviral
      efficacy of tenofovir (TDF)/LAM combination therapy versus TDF monotherapy in LAM
      resistant chronic hepatitis B (CHB) patients who failed to respond to LAM plus
      ADV rescue therapy. METHODS: Among 108 patients with LAM-resistant CHB who had a
      partial virologic response (VR) to LAM and ADV combination therapy, Eighty one
      patients were finally included in this study. FINDINGS: Resistance to ADV (ADV-R)
      was present in 32 patients (39.5%), and the remaining 49 patients (60.5%) had a
      partial virologic response to LAM/ADV combination (ADV-P). The study subjects
      were treated with TDF alone (n=15) or TDF/LAM combination (n=66). VR was achieved
      in 61 patients (75.3%). The rates of VR at 6 and 12 months were not significantly
      different between TDF monotherapy and TDF/LAM combination therapy groups (46.7
      vs. 68.2% at 6 months, and 66.7 vs. 75.9% at 12 months, log-rank P=0.357).
      Treatment efficacy of TDF alone or TDF/LAM combination was not statistically
      different according to pre-existing ADV or LAM resistant strains. In multivariate
      analysis, absolute HBV DNA levels at the start of TDF rescue treatment (P<0.001;
      OR, 0.556; 95% CI, 0.422-0.731) were the only significantly associated with VR.
      IMPLICATIONS: TDF monotherapy was as effective as TDF/LAM combination therapy in
      maintaining viral suppression in patients with LAM-resistant patients who failed
      to respond to LAM/ADV combination therapy.

PMID- 25956354
TI  - Opening toward life: experiences of basic body awareness therapy in persons with
      major depression.
AB  - Although there is a vast amount of research on different strategies to alleviate
      depression, knowledge of movement-based treatments focusing on body awareness is
      sparse. This study explores the experiences of basic body awareness therapy
      (BBAT) in 15 persons diagnosed with major depression who participated in the
      treatment in a randomized clinical trial. Hermeneutic phenomenological
      methodology inspired the approach to interviews and data analysis. The
      participants' experiences were essentially grasped as a process of enhanced
      existential openness, opening toward life, exceeding the tangible corporeal
      dimension to also involve emotional, temporal, and relational aspects of life.
      Five constituents of this meaning were described: vitality springing forth,
      grounding oneself, recognizing patterns in one's body, being acknowledged and
      allowed to be oneself, and grasping the vagueness. The process of enhanced
      perceptual openness challenges the numbness experienced in depression, which can
      provide hope for change, but it is connected to hard work and can be emotionally
      difficult to bear. Inspired by a phenomenological framework, the results of this
      study illuminate novel clinical and theoretical insight into the meaning of BBAT
      as an adjunctive approach in the treatment of depression. 

PMID- 25956355
TI  - Metabolic changes in type 2 diabetes are reflected in peripheral blood cells,
      revealing aberrant cytotoxicity, a viral signature, and hypoxia inducible factor
      activity.
AB  - BACKGROUND: Metabolic syndrome (MetS) is characterized by central obesity,
      insulin resistance, dysglycemia, and a pro-atherogenic plasma lipid profile. MetS
      creates a high risk for development of type 2 diabetes (T2DM) and cardiovascular
      disease (CVD), presumably by altering inflammatory responses. Presently, it is
      unknown how the chronic metabolic disturbances in acute hyperglycemia, MetS and
      T2DM affect the immune activity of peripheral blood cells. METHODS: We performed
      genome-wide expression analysis of peripheral blood cells obtained from patients
      with T2DM (n = 6) and age-, sex- , BMI- and blood pressure-matched obese
      individuals with MetS (n = 4) and lean healthy normoglycemic controls (n = 3),
      both under fasting conditions and after controlled induction of acute
      hyperglycemia during a 70 min hyperglycemic clamp. Differential gene expression
      during fasting conditions was confirmed by real-time PCR, for which we included
      additional age-, sex-, BMI-, and blood pressure-matched obese individuals with (n
      = 4) or without (n = 4) MetS. RESULTS: Pathway and Gene ontology analysis applied
      to baseline expression profiles of peripheral blood cells from MetS and T2DM
      patients revealed metabolic changes, highly similar to a reoviral infection gene
      signature in T2DM patients. Transcription factor binding site analysis indicated
      that increased HIF-1alpha activity, a transcription factor induced by either
      hypoxia or oxidative stress, is responsible for this aberrant metabolic profile
      in peripheral blood cells from T2DM patients. Acute hyperglycemia in healthy
      controls resulted in reduced expression of cytotoxicity-related genes,
      representing NK- and CD8(+) cells. In obese controls, MetS and especially T2DM
      patients, baseline expression of genes involved in cytotoxicity was already low,
      compared to healthy controls and did not further decrease upon acute
      hyperglycemia. CONCLUSIONS: The reduced activity of cytotoxic genes in T2DM is
      explained by chronic hyperglycemia, but its acute effects are restricted to
      healthy controls. Genome expression of circulating leukocytes from T2DM patients
      differs from MetS individuals by a specific reovirus signature. Our data thus
      suggest a role for suppressed anti-viral capacity in the etiology of diabetes.

PMID- 25956356
TI  - Zodiac: A Comprehensive Depiction of Genetic Interactions in Cancer by
      Integrating TCGA Data.
AB  - BACKGROUND: Genetic interactions play a critical role in cancer development.
      Existing knowledge about cancer genetic interactions is incomplete, especially
      lacking evidences derived from large-scale cancer genomics data. The Cancer
      Genome Atlas (TCGA) produces multimodal measurements across genomics and features
      of thousands of tumors, which provide an unprecedented opportunity to investigate
      the interplays of genes in cancer. METHODS: We introduce Zodiac, a computational
      tool and resource to integrate existing knowledge about cancer genetic
      interactions with new information contained in TCGA data. It is an evolution of
      existing knowledge by treating it as a prior graph, integrating it with a
      likelihood model derived by Bayesian graphical model based on TCGA data, and
      producing a posterior graph as updated and data-enhanced knowledge. In short,
      Zodiac realizes "Prior interaction map + TCGA data -> Posterior interaction map."
      RESULTS: Zodiac provides molecular interactions for about 200 million pairs of
      genes. All the results are generated from a big-data analysis and organized into
      a comprehensive database allowing customized search. In addition, Zodiac provides
      data processing and analysis tools that allow users to customize the prior
      networks and update the genetic pathways of their interest. Zodiac is publicly
      available at www.compgenome.org/ZODIAC. CONCLUSIONS: Zodiac recapitulates and
      extends existing knowledge of molecular interactions in cancer. It can be used to
      explore novel gene-gene interactions, transcriptional regulation, and other types
      of molecular interplays in cancer.

PMID- 25956357
TI  - Detecting overall survival benefit derived from survival postprogression rather
      than progression-free survival.
AB  - Broglio and Berry (2009) examined the impact of survival postprogression (SPP) on
      overall survival (OS) when progression-free survival (PFS) was used to assess
      treatment effect in metastatic cancer. Their simulation studies found no
      statistical difference in OS because of dilution effect from SPP, although there
      was a statistical difference in PFS between treatment arms. Recently, two phase
      III clinical trials showed efficacy of experimental treatments in OS, but not
      PFS. These results seem counterintuitive, because it may be reasonable to
      consider that the effect of treatment in prolonging PFS can influence OS
      prolongation. We conducted simulations to examine the role of SPP in OS under the
      assumption that only SPP, and not PFS, differed between treatment arms. We also
      explored the impact of patient heterogeneity on the OS analysis. Our study offers
      a reasonable explanation for the two phase III trials and recommends further
      discussion of PFS as an adequate endpoint and what role SPP might play in OS to
      evaluate current treatment regimens. 

PMID- 25956358
TI  - Dysregulation of energy balance by trichothecene mycotoxins: Mechanisms and
      prospects.
AB  - Trichothecenes are toxic metabolites produced by fungi that constitute a
      worldwide hazard for agricultural production and both animal and human health.
      More than 40 countries have introduced regulations or guidelines for food and
      feed contamination levels of the most prevalent trichothecene, deoxynivalenol
      (DON), on the basis of its ability to cause growth suppression. With the
      development of analytical tools, evaluation of food contamination and exposure
      revealed that a significant proportion of the human population is chronically
      exposed to DON doses exceeding the provisional maximum tolerable daily dose.
      Accordingly, a better understanding of trichothecene impact on health is needed.
      Upon exposure to low or moderate doses, DON and other trichothecenes induce
      anorexia, vomiting and reduced weight gain. Several recent studies have addressed
      the mechanisms by which trichothecenes induce these symptoms and revealed a
      multifaceted action targeting gut, liver and brain and causing dysregulation in
      neuroendocrine signaling, immune responses, growth hormone axis, and central
      neurocircuitries involved in energy homeostasis. Newly identified trichothecene
      toxicosis biomarkers are just beginning to be exploited and already open up new
      questions on the potential harmful effects of chronic exposure to DON at
      apparently asymptomatic very low levels. This review summarizes our current
      understanding of the effects of DON and other trichothecenes on food intake and
      weight growth. 

PMID- 25956359
TI  - A theoretical model of the endothelial cell morphology due to different
      waveforms.
AB  - Endothelial cells are key units in the regulatory biological process of blood
      vessels. They represent an interface to transmit variations on the fluid dynamic
      changes. They are able to adapt its cytoskeleton, by means of microtubules
      reorientation and F-actin reorganization, due to new mechanical environments.
      Moreover, they are responsible for initiating a huge cascade of biological
      processes, such as the release of endothelins (ET-1), in charge of the
      constriction of the vessel and growth factors such as TGF-beta and PDGF. Although
      a huge efforts have been made in the experimental characterization and
      description of these two issues the computational modeling has not gained such an
      attention. In this work we study the 3D remodeling of endothelial cells based on
      the main features of blood flow. In particular we study how different oscillatory
      shear index and the time average wall shear stresses modify the endothelial cell
      shape. We found our model fitted the experimental works presented before in in
      vitro studies. We also include our model within a computational fluid dynamics
      simulation of a carotid artery to evaluate endothelial cell shape index which is
      a key predictor of atheroma plaque formation. Moreover, our approach can be
      coupled with models of collagen and smooth muscle cell growth, where remodeling
      and the associated release of chemical substance are involved. 

PMID- 25956360
TI  - Seminal role of deletion of amino acid residues in H1-S2 and S-loop regions in
      eukaryotic beta-tubulin investigated from docking and dynamics perspective.
AB  - Tubulin is the fundamental unit of microtubules. It is reported to effect
      different functions like cell division, chromosomal segregation, motility and
      intracellular transportation. alpha- and beta-tubulin associate laterally and
      longitudinally to form protofilaments. Both the subunits are structurally
      identical to each other except for the deletions reported in H1-S2 and S loop
      regions in eukaryotic beta-tubulin. These deletions mimic the ancestral tubulin
      protein named Latest Common FtsZ-Tubulin Ancestor (LCFTA) with a shorter S-loop
      region resulting in weak dimerization. However, in eukaryotic beta tubulin, the
      significance of this shorter region remains elusive till date. The main objective
      of this study was to model variants of beta tubulin (betamut1, betamut2 and
      betamut3) with inserts that lengthened the loop, and to compare them with the
      native alpha- and beta-subunits to understand their biological significance.
      Further, one more mutant was modeled with the intention of understanding the
      counter effect of additional deletion of amino acid residues from both H1-S2 and
      S-loop regions; this mutant was designated as betamut4. Our study confirms that
      the insertion of amino acid residues considerably increases the protein-protein
      interactions in betamut1-betamut1, betamut2-betamut2 and betamut3-betamut3
      compared to their native beta-subunit. Similarly, the binding affinity of GTP
      also increases in betamut2 and betamut3 as compared to the wild type. However,
      these deletions result in decreased protein-protein and ligand interactions in
      wild beta tubulin and betamut4, as compared to betamut1, betamut2,and betamut3.
      Therefore, we conclude here that residual inserts in the H1-S2 and S loop sub
      segments bring about conformational changes in regions critically involved in
      lateral interactions and in the nucleotide binding site, thus altering the
      binding affinities between the dimers and the ligands. Regarding the biological
      importance of such deletions in wild beta tubulin, these deletions result in
      flexible M-loop leading to weak protein-protein interaction. This could be an
      adaptive feature playing a crucial role in protofilament dissociation during GTP
      hydrolysis, because of weak dimerization. 

PMID- 25956361
TI  - Primary cilia mechanics affects cell mechanosensation: A computational study.
AB  - Primary cilia (PC) are mechanical cell structures linked to the cytoskeleton and
      are central to how cells sense biomechanical signals from their environment.
      However, it is unclear exactly how PC mechanics influences cell mechanosensation.
      In this study we investigate how the PC mechanical characteristics are involved
      in the mechanotransduction process whereby cilium deflection under fluid flow
      induces strains on the internal cell components that regulate the cell's
      mechanosensitive response. Our investigation employs a computational approach in
      which a finite element model of a cell consisting of a nucleus, cytoplasm,
      cortex, microtubules, actin bundles and a primary cilium was used together with a
      finite element representation of a flow chamber. Fluid-structure interaction
      analysis was performed by simulating perfusion flow of 1mm/s on the cell model.
      Simulations of cells with different PC mechanical characteristics, showed that
      the length and the stiffness of PC are responsible for the transmission of
      mechanical stimuli to the cytoskeleton. Fluid flow deflects the cilium, with the
      highest strains found at the base of the PC and in the cytoplasm. The PC
      deflection created further strains on the cell nucleus but did not influence
      microtubules and actin bundles significantly. Our results indicate that PC
      deflection under fluid flow stimulation transmits mechanical strain primarily to
      other essential organelles in the cytoplasm, such as the Golgi complex, that
      regulate cells' mechanoresponse. The simulations further suggest that cell
      mechanosensitivity can be altered by targeting PC length and rigidity. 

PMID- 25956362
TI  - Genome-wide screen of ovary-specific DNA methylation in polycystic ovary
      syndrome.
AB  - OBJECTIVE: To compare genome-wide DNA methylation profiles in ovary tissue from
      women with polycystic ovary syndrome (PCOS) and healthy controls. DESIGN: Case
      control study matched for age and body mass index. SETTING: University-affiliated
      hospital. PATIENT(S): Ten women with PCOS who underwent ovarian drilling to
      induce ovulation and 10 healthy women who were undergoing laparoscopic
      sterilization, hysterectomy for benign conditions, diagnostic laparoscopy for
      pelvic pain, or oophorectomy for nonovarian indications. INTERVENTION(S): None.
      MAIN OUTCOME MEASURE(S): Genome-wide DNA methylation patterns determined by
      immunoprecipitation and microarray (MeDIP-chip) analysis. RESULT(S): The
      methylation levels were statistically significantly higher in CpG island shores
      (CGI shores), which lie outside of core promoter regions, and lower within gene
      bodies in women with PCOS relative to the controls. In addition, high CpG content
      promoters were the most frequently hypermethylated promoters in PCOS ovaries but
      were more often hypomethylated in controls. Second, 872 CGIs, specifically
      methylated in PCOS, represented 342 genes that could be associated with various
      molecular functions, including protein binding, hormone activity, and
      transcription regulator activity. Finally, methylation differences were validated
      in seven genes by methylation-specific polymerase chain reaction. These genes
      correlated to several functional families related to the pathogenesis of PCOS and
      may be potential biomarkers for this disease. CONCLUSION(S): Our results
      demonstrated that epigenetic modification differs between PCOS and normal
      ovaries, which may help to further understand the pathophysiology of this
      disease.

PMID- 25956363
TI  - Ectopic pregnancy after in vitro fertilization: differences between fresh and
      frozen-thawed cycles.
AB  - OBJECTIVE: To evaluate whether the uterine environment is associated with the
      risk of ectopic implantation by comparing outcomes of fresh and frozen-thawed
      embryo transfers. DESIGN: Retrospective historical cohort. SETTING: Not
      applicable. PATIENT(S): We used the Society for Assisted Reproductive
      Technologies (SART) database to identify pregnancies that resulted from fresh and
      frozen blastocyst transfers from 2008 to 2011. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): We determined the proportion of ectopic (EP) versus
      intrauterine-only pregnancies resulting from fresh or frozen embryo transfers in
      autologous and donor-oocyte cycles. Generalized estimation equation regression
      models were used to adjust for maternal and treatment characteristics. RESULT(S):
      Among 103,070 cycles that resulted in a clinical pregnancy, 1.38% were ectopic.
      The odds of EP were 65% lower in women who had a frozen compared with a fresh
      transfer in autologous cycles. Donor-oocyte transfers had lower odds of EP
      compared with autologous cycles, with no difference between fresh and frozen
      donor transfers. Women who had both a fresh and a frozen transfer with autologous
      oocytes had a higher risk of EP in their fresh cycles compared with their frozen
      cycles. CONCLUSION(S): Embryo transfers in cycles without ovarian
      hyperstimulation, such as frozen or donor cycles, were associated with lower
      rates of EP compared with fresh autologous cycles, suggesting that a difference
      in the tubal-uterine environment contributes to abnormal implantation after IVF.

PMID- 25956364
TI  - Use of reproductive technology for sex selection for nonmedical reasons.
AB  - Because these practices are ethically controversial, clinics are encouraged to
      develop and make available their policies on the provision of nonmedical sex
      selection, and to accommodate their employees' decisions about whether or not to
      participate in such treatment. Practitioners offering assisted reproductive
      services are under no ethical obligation to provide or refuse to provide
      nonmedically indicated methods of sex selection. This document replaces two
      documents previously published by the ASRM Ethics Committee, titled, "Sex
      selection and preimplantation genetic diagnosis" (Fertil Steril 2004;82:S245-8)
      and "Preconception gender selection for nonmedical reasons" (Fertil Steril
      2004;82:S232-5). 

PMID- 25956365
TI  - Health-related quality of life in pregnancy and postpartum among women with
      assisted conception in Canada.
AB  - OBJECTIVE: To study the effects of mode of conception (spontaneous vs. assisted)
      on health-related quality of life (HRQoL) throughout pregnancy and in the
      postpartum period. DESIGN: Secondary analysis of data from the All Our Babies
      cohort. SETTING: Not applicable. PATIENT(S): A total of 243 women with assisted
      conception and 3,309 women with spontaneous conception. INTERVENTION(S): Short
      Form 12 (SF-12) health survey administered by means of questionnaires at <25
      weeks, 34-36 weeks of gestation, and 4 months postpartum. MAIN OUTCOME
      MEASURE(S): Changes in the SF-12 Physical (PCS) and Mental (MCS) Component
      Summary scores from pregnancy to postpartum. RESULT(S): The PCS scores were lower
      during pregnancy and at <25 weeks and 34-36 weeks of gestation among women with
      assisted conception, but were equivalent to those of women with spontaneous
      conception by 4 months postpartum. The MCS scores were higher at <25 weeks among
      women with assisted conception, but by 34-36 weeks of gestation and at 4 months
      postpartum they were similar regardless of the method of conception. Analysis of
      covariance showed no significant differences for the changes in PCS and MCS
      scores from pregnancy to postpartum between assisted and spontaneous conception
      groups, after adjusting for covariates. CONCLUSION(S): Women with assisted
      conception may report lower physical and better mental health during pregnancy
      than women with spontaneous conception. At 4 months postpartum, there were no
      differences in self-reported HRQoL between modes of conception. Women with
      assisted conception may benefit from support and reassurance that perception of
      suboptimal health may improve over pregnancy and into the postpartum period.

PMID- 25956366
TI  - Laparoscopic vaginoplasty using a single peritoneal flap: 10 years of experience
      in the creation of a neovagina in patients with Mayer-Rokitansky-Kuster-Hauser
      syndrome.
AB  - OBJECTIVE: To assess anatomical and functional outcomes of a novel laparoscopic
      vaginoplasty technique using a single peritoneal flap (SPF) in patients with
      Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. DESIGN: Prospective follow-up
      study. SETTING: University-based tertiary-care hospital. PATIENT(S): Patients
      with MRKH syndrome (n = 83) and randomly selected frequency-matched age
      comparable healthy women serving as controls (n = 85). INTERVENTION(S): From
      March 2004 to March 2014, a total of 83 patients with MRKH syndrome underwent
      laparoscopic vaginoplasty using an SPF. MAIN OUTCOME MEASURE(S): Intraoperative
      parameters, postoperative parameters, and anatomical outcomes were recorded. The
      functional results of patients who became sexually active were assessed using the
      Female Sexual Function Index (FSFI) questionnaire and were compared with those of
      the controls. RESULT(S): Laparoscopic vaginoplasty using an SPF was successfully
      performed in all 83 patients, with no intraoperative complications. The mean
      operative time and intraoperative blood loss were, respectively, 71.2 +/- 18.9
      minutes and 88.5 +/- 57.2 ml. The mean length and width of the neovagina at the 6
      month follow-up examination were, respectively, 8.2 +/- 0.8 cm and 3.0 +/- 0.6
      cm. Anatomical success was achieved in all patients. At 12 months after surgery,
      functional success, as assessed by the FSFI questionnaire, was achieved in 95.3%
      of patients. The FSFI scores did not differ significantly between patients with
      MRKH and healthy women in a control group. CONCLUSION(S): Laparoscopic
      vaginoplasty using an SPF may be a feasible and effective approach that has
      satisfactory anatomical and functional outcomes for patients with MRKH syndrome.

PMID- 25956367
TI  - PON1 polymorphisms are associated with polycystic ovary syndrome susceptibility,
      related traits, and PON1 activity in Indian women with the syndrome.
AB  - OBJECTIVE: To investigate the association of paraoxonase 1 (PON1) polymorphisms
      (L55M and Q192R) with polycystic ovary syndrome (PCOS) susceptibility and its
      related traits in Indian women. DESIGN: Case-control study. SETTING: Academic
      research institute, infertility, and endocrinology clinics. PATIENT(S): Controls
      (n = 326), women with PCOS (n = 482). INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Genotypic and allelic frequency distribution, genotype-phenotype
      association, different PON1 activities (lactonase, arylesterase, and
      paraoxonase). RESULT(S): The genotypic and allelic frequency distributions of the
      L55M polymorphism were significantly different between lean controls and lean
      women with PCOS, and this polymorphism reduced the risk of PCOS development in
      lean but not in obese Indian women. Furthermore, this polymorphism was
      significantly associated with decreased 2-hour glucose, apolipoprotein B, free
      and bioavailable T, and free androgen index concurrent with increased sex hormone
      binding globulin (SHBG) and FSH levels only in lean women with PCOS. However,
      Q192R polymorphism showed comparable genotypic frequency distribution between
      controls and women with PCOS. PON1 lactonase and arylesterase activities were
      significantly decreased in women with PCOS compared with controls. PON1
      polymorphisms were shown to influence its activities. CONCLUSION(S): Our study
      showed that L55M, but not Q192R, polymorphism is significantly associated with
      reduced PCOS susceptibility only in lean women and also impacts glucose
      metabolism, lipid parameters, and hyperandrogenemia in them. Our study therefore
      suggests the possibility of differential genetic pathophysiology of PCOS between
      lean and obese women.

PMID- 25956368
TI  - Adverse pregnancy outcomes after in vitro fertilization: effect of number of
      embryos transferred and plurality at conception.
AB  - OBJECTIVE: To evaluate risks for adverse pregnancy outcomes by number of embryos
      transferred (ET) and fetal heartbeats (FHB) in assisted reproductive technology
      conceived singleton live births. DESIGN: Longitudinal cohort using cycles
      reported to the Society for Assisted Reproductive Technology Clinic Outcomes
      Reporting System between 2004 and 2008 among women who were treated and gave
      birth in Massachusetts. SETTING: Not applicable. PATIENT(S): Assisted
      reproductive technology data on 6,073 births between 2004 and 2008 were linked to
      vital records and hospital data. Likelihood of ET >=3 vs. 1-2, FHB >1 vs. 1, and
      risks of preterm birth (PTB, <37 weeks' gestation), low birth weight (LBW, <2,500
      g), and small-for-gestational-age birth weight (SGA, <10th percentile) with FHB
      >1 were modeled with binary logistic regression using a backward-stepping
      algorithm, and presented as adjusted odds ratios (95% confidence intervals).
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): ET >=3, FHB >1, PTB, LBW, and
      SGA. RESULT(S): Higher ET was significantly more likely with older maternal age,
      intracytoplasmic sperm injection, assisted hatching, cleavage-stage embryos, and
      thawed embryos. The likelihood of FHB >1 with >=3 ET vs. 1-2 ET was 2.04 (1.68
      2.48). Risks of PTB and LBW with FHB >1 were 1.63 (1.27-2.09) and 1.81 (1.36
      2.39), respectively; the risk of SGA was not significant. Nulliparity was
      associated with higher risks of PTB (1.34 [1.12-1.59]), LBW (1.48 [1.20-1.83]),
      and SGA (2.17 [1.69-2.78]). CONCLUSION(S): Number of embryos transferred was
      strongly associated with FHBs, with twice the risk of FHB >1 with >=3 ET vs. 1-2
      ET. Increasing FHBs were associated with significantly greater risks for PTB and
      LBW outcomes.

PMID- 25956369
TI  - Paternal age and mental health of offspring.
AB  - The influence of paternal age on the risk for sporadic forms of Mendelian
      disorders is well known, but a burgeoning recent literature demonstrates, in
      addition, a paternal age effect for complex neuropsychiatric conditions,
      including schizophrenia, autism, bipolar disorder, and even for learning
      potential, expressed as intelligence. Mental illness is costly to patients, their
      family, and the public health system, accounting for the largest portion of
      disability costs in our economy. The delayed onset of neuropsychiatric conditions
      and lack of physical manifestations at birth are common frequencies in the
      population that have obscured the recognition that a portion of the risks for
      mental conditions is associated with paternal age. Identification of these risk
      pathways may be leveraged for knowledge about mental function and for future
      screening tests. However, only a small minority of at-risk offspring are likely
      to have such a psychiatric or learning disorder attributable to paternal age,
      including the children of older fathers. 

PMID- 25956370
TI  - Medroxyprogesterone acetate is an effective oral alternative for preventing
      premature luteinizing hormone surges in women undergoing controlled ovarian
      hyperstimulation for in vitro fertilization.
AB  - OBJECTIVE: To investigate the use of medroxyprogesterone acetate (MPA) to prevent
      LH surge during controlled ovarian hyperstimulation (COH) and to compare cycle
      characteristics and pregnancy outcomes in subsequently frozen-thawed ET (FET)
      cycles. DESIGN: A prospective controlled study. SETTING: Tertiary-care academic
      medical center. PATIENT(S): Three hundred patients undergoing
      IVF/intracytoplasmic sperm injection treatment. INTERVENTION(S): In the study
      group, hMG and MPA were administered simultaneously beginning on cycle day 3.
      Ovulation was induced with a GnRH agonist or cotriggered by a GnRH agonist and
      hCG when dominant follicles matured. A short protocol was used in the control
      group. Viable embryos were cryopreserved for later transfer in both protocols.
      MAIN OUTCOME MEASURE(S): The primary outcome measure was the number of oocytes
      retrieved. Secondary outcomes included the number of mature oocytes, the
      incidence of premature LH surge, and clinical pregnancy outcomes from FETs.
      RESULT(S): The number of oocytes retrieved in the study group was similar to
      those in the controls (9.9 +/- 6.7 vs. 9.0 +/- 6.0), and higher doses of hMG were
      administered. In the study group, LH suppression persisted during ovarian
      stimulation, and the incidence of premature LH surge was 0.7% (1/150). No
      statistically significant differences were found in the clinical pregnancy rates
      (47.8% vs. 43.3%), implantation rates (31.9% vs. 27.7%), and live-birth rates
      (42.6% vs. 35.5%) in the study group and controls. CONCLUSION(S): The results
      show that MPA is an effective oral alternative for the prevention of premature LH
      surge in woman undergoing COH. This finding will help establish a new regimen for
      ovarian stimulation in combination with embryo cryopreservation. CLINICAL TRIAL
      REGISTRATION NUMBER: ChiCTR-ONRC-14004419.

PMID- 25956371
TI  - Safety of ovarian conservation and fertility preservation in advanced borderline
      ovarian tumors.
AB  - OBJECTIVE: To assess the impact of a fertility-sparing approach on disease
      recurrence in women with advanced borderline ovarian tumors. DESIGN: Historic
      cohort study. SETTING: A tertiary referral center for gynecological oncology
      patients and a university teaching hospital. PATIENT(S): Consecutive patients
      with advanced borderline ovarian tumors defined as stage IC and above, treated at
      a single institution during a span of 30 years. INTERVENTION(S): Data on surgical
      approach (e.g., fertility sparing, ovarian conserving) as well as histopathology,
      disease stage, CA-125 level, and use of chemotherapy were collected from the
      medical records, and their impact on disease recurrence was assessed. MAIN
      OUTCOME MEASURE(S): Recurrence-free interval. Its association with the type of
      surgery and with other clinical and pathological features was assessed using the
      Kaplan Meier and Cox proportional hazards methods. RESULT(S): Fifty-nine patients
      with advanced disease were identified. Median follow-up was 55.3 months. Mean age
      at diagnosis was 35 years. Most of the tumors (51, 84.4%) had serous histology.
      Twenty-seven patients (45.8%) developed recurrences and 6 (10%) died of their
      disease. Mean time to recurrence was 30.6 months. Of 44 women <=40 years, 33
      (75%) had a fertility-sparing procedure. Fertility preservation was not
      associated with disease recurrence. A total of 34 pregnancies and 26 live births
      were documented among 21 patients attempting conception. CONCLUSION(S):
      Borderline ovarian tumors carry a favorable prognosis, even at an advanced stage.
      Fertility preservation was not found to be associated with an increased risk of
      relapse in young patients with advanced disease, and may be reasonably
      considered.

PMID- 25956373
TI  - High responders and patients with a good prognosis are not immune to the negative
      impact on live birth rate of elevated P on the day of triggering.

PMID- 25956372
TI  - Whole-exome sequencing identifies novel homozygous mutation in NPAS2 in family
      with nonobstructive azoospermia.
AB  - OBJECTIVE: To investigate the genetic cause of nonobstructive azoospermia (NOA)
      in a consanguineous Turkish family through homozygosity mapping followed by
      targeted exon/whole-exome sequencing to identify genetic variations. DESIGN:
      Whole-exome sequencing (WES). SETTING: Research laboratory. PATIENT(S): Two
      siblings in a consanguineous family with NOA. INTERVENTION(S): Validating all
      variants passing filter criteria with Sanger sequencing to confirm familial
      segregation and absence in the control population. MAIN OUTCOME MEASURE(S):
      Discovery of a mutation that could potentially cause NOA. RESULT(S): A novel
      nonsynonymous mutation in the neuronal PAS-2 domain (NPAS2) was identified in a
      consanguineous family from Turkey. This mutation in exon 14 (chr2: 101592000 C>G)
      of NPAS2 is likely a disease-causing mutation as it is predicted to be damaging,
      it is a novel variant, and it segregates with the disease. Family segregation of
      the variants showed the presence of the homozygous mutation in the three brothers
      with NOA and a heterozygous mutation in the mother as well as one brother and one
      sister who were both fertile. The mutation is not found in the single-nucleotide
      polymorphism database, the 1000 Genomes Project, the Baylor College of Medicine
      cohort of 500 Turkish patients (not a population-specific polymorphism), or the
      matching 50 fertile controls. CONCLUSION(S): With the use of WES we identified a
      novel homozygous mutation in NPAS2 as a likely disease-causing variant in a
      Turkish family diagnosed with NOA. Our data reinforce the clinical role of WES in
      the molecular diagnosis of highly heterogeneous genetic diseases for which
      conventional genetic approaches have previously failed to find a molecular
      diagnosis.

PMID- 25956374
TI  - Human immunodeficiency virus (HIV) and infertility treatment: a committee
      opinion.
AB  - Human immunodeficiency virus (HIV) is a serious but manageable chronic disease
      that affects persons of reproductive age, many of whom express a desire for
      biologic parenthood. This document is a revision of the original document of the
      same name, last published in 2010 (Fertil Steril 2010;94:11-5). 

PMID- 25956375
TI  - A novel 47.2 Mb duplication on chromosomal bands Xq21.1-25 associated with mental
      retardation.
AB  - We present array comparative genomic hybridization (aCGH) characterization of a
      novel Xq21.1-25 duplication in a 2-year-old girl with facial dysmorphism, mental
      retardation and short stature. Analysis of aCGH results revealed a 47,232kb
      duplication region that harbored 231 RefSeq genes, including 32 OMIM genes. Ten
      genes (i.e., ZNF711, SRPX2, RAB40AL, MID2, ACSL4, PAK3, UBE2A, UPF3B, CUL4B, and
      GRIA3) in the duplication interval have been associated with mental retardation.
      We discuss the genotype-phenotype correlation in this case. Our case provides
      evidence for an association of mental retardation with X chromosome duplication. 

PMID- 25956376
TI  - Evolution of a novel nuclear receptor subfamily with emphasis on the member from
      the Pacific oyster Crassostrea gigas.
AB  - Nuclear receptors (NRs) belong to the transcription factor superfamily that
      regulates development, homeostasis, differentiation, and reproduction in
      metazoans via control of gene expression. Recently, rapid advances in genome
      projects on various metazoans have provided new opportunities for studying the
      evolution and function of NRs. Typically structured NRs are divided into six
      subfamilies. Here, the gene for a typically structured NR (CgNR8A1) was cloned
      from the Pacific oyster Crassostrea gigas. However, this novel receptor could not
      be assigned to a known NR subfamily. By data mining, nine other CgNR8A1 gene
      homologs were identified in metazoans such as cnidarians, mollusks, annelids,
      echinoderms, hemichordates, and cephalochordates. Phylogenetic analysis showed
      that these receptors belonged to a novel NR subfamily, hereafter designated as
      NR8. Evolutionary analysis revealed that the NR8 subfamily was phylogenetically
      the third-oldest NR subfamily, and it originated from a common ancestor of
      Eumetazoa; several gene loss events occurred independently in ancestors of
      vertebrates, ecdysozoans, and platyhelminths, which do not have NR8 members.
      Furthermore, the function of CgNR8A1 was investigated to provide an insight into
      the functions of this novel NR subfamily. A nuclear localization signal peptide,
      GKHRNKKPRLD, was identified in CgNR8A1, and a recombinant full-length protein of
      CgNR8A1 was localized in the nuclei of HeLa cells. The mRNA expression profile of
      CgNR8A1 suggested that it might be involved in the embryogenesis of C. gigas. The
      electrophoretic mobility shift assay showed that CgNR8A1 binds strongly to
      conserved DNA core motifs DR0, DR2, and DR4 and weakly to DR1, DR3, DR5, Half,
      and Pal0. In summary, the novel NR8 subfamily identified in this study improves
      our understanding of NR evolution, and the functional analysis of CgNR8A1
      provided further insights into the functions of NR8A1s. 

PMID- 25956377
TI  - Testing the Feasibility and Psychometric Properties of a Mobile Diary (myWHI) in
      Adolescents and Young Adults With Headaches.
AB  - BACKGROUND: Headaches are prevalent among teens and young adults. Self-monitoring
      is essential for managing headaches and can be accomplished with the help of
      electronic headache diaries. An increasing number of electronic headache diaries
      exist, yet the absence of quality standards compromises their use for research
      and clinical purposes. OBJECTIVE: Our goal was to develop and test the usability,
      feasibility, and psychometric properties of an electronic diary iPhone
      application for self-monitoring by adolescents and young adults with headaches.
      METHODS: We used an iterative participatory design to develop and test our
      electronic headache diary. Participants aged 14-28 years old with recurrent
      headaches were recruited internationally. Screening and consent were conducted
      online. Following completion of an online pre-questionnaire, participants
      downloaded the diary to use in their natural environment for 14 days. An online
      post-questionnaire was completed following testing. The diary's usability and
      feasibility were tested first and determined to be complete when improvements to
      the diary did not result in a statistically significant impact on indicators of
      feasibility and adherence. Interviews were conducted with participants of
      usability and feasibility testing. The psychometric properties of the diary were
      then tested, and a case study analysis of one participant was completed. RESULTS:
      Three cycles to test the usability and feasibility were conducted. Each cycle
      included 11-19 unique participants ranging in age from 16 to 28 years. Following
      the testing period for each cycle, 15% to 25% of participants took part in the
      post-cycle interview. Participants perceived the final version of the diary as
      useful, easy to learn, and efficient to use. Psychometric properties were then
      tested with a sample of 65 participants (6 aged 14-17 years old; 59 aged 18-28
      years old). All items in the diary had substantial between- and within-subjects
      variability (percent of variance for the two participant groups ranged from 20.64
      to 75.60 and 23.74 to 79.21, respectively). Moreover, the Migraine Disability
      Assessment (MIDAS) included in the diary had adequate between-subjects
      reliability (R1F=0.66, RKF=0.98), but low within-subjects reliability (RC=0.51).
      Critical elements of the diary demonstrated adequate convergent and concurrent
      validity, particularly in the older age group (18-28 years). The validity of some
      critical elements of the diary could not be explored in the younger age group due
      to the small subgroup size. The case study provides an example of the potential
      utility of the diary. CONCLUSIONS: Our electronic headache diary was shown to be
      a usable and feasible self-monitoring tool when used by adolescents and young
      adults with headaches for 14 days. This study provides preliminary support of its
      psychometric properties. Our diary has the potential for helping users to better
      understand their headaches and, consequently, to change behaviors to improve self
      management of their headaches. Its effectiveness as a component of an
      intervention will be the focus of future research.

PMID- 25956378
TI  - Classification of fungal and bacterial lytic polysaccharide monooxygenases.
AB  - BACKGROUND: Lytic polysaccharide monooxygenases are important enzymes for the
      decomposition of recalcitrant biological macromolecules such as plant cell wall
      and chitin polymers. These enzymes were originally designated glycoside hydrolase
      family 61 and carbohydrate-binding module family 33 but are now classified as
      auxiliary activities 9, 10 and 11 in the CAZy database. To obtain a systematic
      analysis of the divergent families of lytic polysaccharide monooxygenases we used
      Peptide Pattern Recognition to divide 5396 protein sequences resembling enzymes
      from families AA9 (1828 proteins), AA10 (2799 proteins) and AA11 (769 proteins)
      into subfamilies. RESULTS: The results showed that the lytic polysaccharide
      monooxygenases have two conserved regions identified by conserved peptides
      specific for each AA family. The peptides were used for in silico PCR discovery
      of the lytic polysaccharide monooxygenases in 79 fungal and 95 bacterial genomes.
      The bacterial genomes encoded 0-7 AA10s (average 0.6). No AA9 or AA11 were found
      in the bacteria. The fungal genomes encoded 0-40 AA9s (average 7) and 0-15 AA11s
      (average 2) and two of the fungi possessed a gene encoding a putative AA10. The
      AA9s were mainly found in plant cell wall-degrading asco- and basidiomycetes in
      agreement with the described role of AA9 enzymes. In contrast, the AA11 proteins
      were found in 36 of the 39 ascomycetes and in only two of the 32 basidiomycetes
      and their abundance did not correlate to the degradation of cellulose and
      hemicellulose. CONCLUSIONS: These results provides an overview of the sequence
      characteristics and occurrence of the divergent AA9, AA10 and AA11 families and
      pave the way for systematic investigations of the of lytic polysaccharide
      monooxygenases and for structure-function studies of these enzymes.

PMID- 25956379
TI  - Combining docking-based comparative intermolecular contacts analysis and k
      nearest neighbor correlation for the discovery of new check point kinase 1
      inhibitors.
AB  - Check point kinase 1 (Chk1) is an important protein in G2 phase checkpoint arrest
      required by cancer cells to maintain cell cycle and to prevent cell death.
      Therefore, Chk1 inhibitors should have potential as anti-cancer therapeutics.
      Docking-based comparative intermolecular contacts analysis (dbCICA) is a new
      three-dimensional quantitative structure activity relationship method that
      depends on the quality and number of contact points between docked ligands and
      binding pocket amino acid residues. In this presented work we implemented a novel
      combination of k-nearest neighbor/genetic function algorithm modeling coupled
      with dbCICA to select critical ligand-Chk1 contacts capable of explaining anti
      Chk1 bioactivity among a long list of inhibitors. The finest set of contacts were
      translated into two valid pharmacophore hypotheses that were used as 3D search
      queries to screen the National Cancer Institute's structural database for new
      Chk1 inhibitors. Three potent Chk1 inhibitors were discovered with IC50 values
      ranging from 2.4 to 69.7 uM.

PMID- 25956380
TI  - Persistence of Methanosaeta populations in anaerobic digestion during process
      instability.
AB  - Anaerobic digestion is a sustainable technology for the treatment of organic
      waste and production of biogas. Acetoclastic methanogenesis accounts for the
      majority of methane production in anaerobic digestion. Therefore, sustaining
      robust acetoclastic methanogens is important for stable process performance. Due
      to faster growth kinetics at high acetate concentrations, it has been considered
      that Methanosarcina would be more prevalent than Methanosaeta in unstable
      anaerobic digestion processes which frequently experience high acetate levels.
      Methanogen population dynamics were monitored in multiple continuous anaerobic
      digesters for 500 days. Results from quantitative polymerase chain reaction
      analysis show that Methanosaeta dominated over Methanosarcina in anaerobic
      digestion at high acetate levels up to 44 mM, suggesting the potential of
      Methanosaeta as a robust and efficient acetoclastic candidate for resilient
      anaerobic methane conversion. Further efforts are needed to identify mechanisms
      contributing to the unexpected competitiveness of these methanogens at high
      acetate levels observed in this study. 

PMID- 25956381
TI  - Three-dimensional spheroid cell culture of umbilical cord tissue-derived
      mesenchymal stromal cells leads to enhanced paracrine induction of wound healing.
AB  - INTRODUCTION: The secretion of trophic factors by mesenchymal stromal cells has
      gained increased interest given the benefits it may bring to the treatment of a
      variety of traumatic injuries such as skin wounds. Herein, we report on a three
      dimensional culture-based method to improve the paracrine activity of a specific
      population of umbilical cord tissue-derived mesenchymal stromal cells (UCX(r))
      towards the application of conditioned medium for the treatment of cutaneous
      wounds. METHODS: A UCX(r) three-dimensional culture model was developed and
      characterized with respect to spheroid formation, cell phenotype and cell
      viability. The secretion by UCX(r) spheroids of extracellular matrix proteins and
      trophic factors involved in the wound-healing process was analysed. The skin
      regenerative potential of UCX(r) three-dimensional culture-derived conditioned
      medium (CM3D) was also assessed in vitro and in vivo against UCX(r) two
      dimensional culture-derived conditioned medium (CM2D) using scratch and
      tubulogenesis assays and a rat wound splinting model, respectively. RESULTS:
      UCX(r) spheroids kept in our three-dimensional system remained viable and
      multipotent and secreted considerable amounts of vascular endothelial growth
      factor A, which was undetected in two-dimensional cultures, and higher amounts of
      matrix metalloproteinase-2, matrix metalloproteinase-9, hepatocyte growth factor,
      transforming growth factor beta1, granulocyte-colony stimulating factor,
      fibroblast growth factor 2 and interleukin-6, when compared to CM2D. Furthermore,
      CM3D significantly enhanced elastin production and migration of keratinocytes and
      fibroblasts in vitro. In turn, tubulogenesis assays revealed increased capillary
      maturation in the presence of CM3D, as seen by a significant increase in
      capillary thickness and length when compared to CM2D, and increased branching
      points and capillary number when compared to basal medium. Finally, CM3D-treated
      wounds presented signs of faster and better resolution when compared to untreated
      and CM2D-treated wounds in vivo. Although CM2D proved to be beneficial, CM3D
      treated wounds revealed a completely regenerated tissue by day 14 after
      excisions, with a more mature vascular system already showing glands and hair
      follicles. CONCLUSIONS: This work unravels an important alternative to the use of
      cells in the final formulation of advanced therapy medicinal products by
      providing a proof of concept that a reproducible system for the production of
      UCX(r)-conditioned medium can be used to prime a secretome for eventual clinical
      applications.

PMID- 25956382
TI  - Evaluation of the Biological Properties and the Enzymatic Stability of
      Glycosylated Luteinizing Hormone-Releasing Hormone Analogs.
AB  - The enzymatic stability, antitumor activity, and gonadotropin stimulatory effects
      of glycosylated luteinizing hormone-releasing hormone (LHRH) analogs were
      investigated in this study. Conjugation of carbohydrate units, including lactose
      (Lac), glucose (GS), and galactose (Gal) to LHRH peptide protected the peptide
      from proteolytic degradation and increased the peptides' half-lives in human
      plasma, rat kidney membrane enzymes, and liver homogenate markedly. Among all
      seven modified analogs, compound 1 (Lac-[Q(1)][w(6)]LHRH) and compound 6 (GS(4)
      [w(6)]LHRH) were stable in human plasma during 4 h of experiment. The half-lives
      of compounds 1 and 6 improved significantly in kidney membrane enzymes (from 3
      min for LHRH to 68 and 103 min, respectively). The major cleavage sites for most
      of the glycosylated compounds were found to be at Trp(3)-Ser(4) and Ser(4)-Tyr(5)
      in compounds 1-5. Compound 6 was hydrolyzed at Ser(4)-Tyr(5) and the sugar
      conjugation site. The antiproliferative activity of the glycopeptides was
      evaluated on LHRH receptor-positive prostate cancer cells. The glycosylated LHRH
      derivatives had a significant growth inhibitory effect on the LNCaP cells after a
      48-h treatment. It was demonstrated that compound 1 significantly increased the
      release of luteinizing hormone (LH) at 5 and 10 nM concentrations and compound 5
      (GS-[Q(1)]LHRH) stimulated the release of follicle-stimulating hormone (FSH) at 5
      nM concentration in dispersed rat pituitary cells (p < 0.05). In our studies,
      compound 1-bearing lactose and D-Trp was the most stable and active and is a
      promising candidate for future preclinical investigations in terms of in vitro
      biological activity and metabolic stability.

PMID- 25956383
TI  - Effect of Device Design and Formulation on the In Vitro Comparability for Multi
      Unit Dose Dry Powder Inhalers.
AB  - The focus of this investigation was to understand the design space to achieve
      comparable in vitro performance of two multi-unit dose dry powder inhalers (DPIs)
      Flixotide(r) Accuhaler(r) (reference product) and MultiHaler(r) (test product).
      Flow field, pressure drop and particle trajectories within the test and reference
      DPI devices were modelled via computational fluid dynamics (CFD). Micronized
      fluticasone propionate (FP) was characterized to determine particle size
      distribution (PSD), specific surface area (SSA) and surface interfacial
      properties using cohesive-adhesive balance (CAB). CFD simulations suggested that
      the pressure drop and airflow velocity in the MultiHaler(r) were greater than
      Accuhaler(r). Two modified test devices (MOD MH 1 and MOD MH 2) were manufactured
      with the introduction of by-pass channels in the airflow path, which achieved
      comparable specific resistance and airflow path between the test and reference
      devices. Assessment of reference product formulation in modified test devices
      suggested that MOD MH 2 achieved comparable in vitro performance to the reference
      product. CAB analysis suggested that adhesion of all FP batches to lactose was
      different, with batch D showing greatest and batch A least adhesion to lactose.
      Test DPI formulations were manufactured using four different batches of FP with
      milled or sieved lactose, and showed that batch A FP formulated with sieved
      lactose in MOD MH 2 device demonstrated the highest degree of similarity to the
      Accuhaler(r) in vitro deposition. Application of CFD modelling and material
      characterization of formulation raw materials enabled the modification of device
      and formulation critical material attributes to create an in vitro comparable
      device/formulation system to the reference product.

PMID- 25956384
TI  - A Review of Clinical Translation of Inorganic Nanoparticles.
AB  - Inorganic nanoparticles are widely used for therapeutic and diagnostic purposes
      as they offer unique features as compared with their organic and polymeric
      counterparts. As such, inorganic nanoparticles represent an exciting opportunity
      to develop drug delivery and imaging systems that are poised to tackle unique
      challenges which are currently unaddressed in clinical settings. Despite these
      clear advantages, very few inorganic nanoparticle systems have entered the
      clinic. Here, we review the current clinical landscape of inorganic nanoparticle
      systems and their opportunities and challenges, with particular emphasis on gold
      , iron-oxide- and silica-based nanoparticle systems. Key examples of inorganic
      nanoparticles that are currently being investigated in the clinic (e.g., trials
      which are recruiting or currently active but not completed) are highlighted,
      along with the preclinical work that these examples have leveraged to transition
      from the lab to the clinic.

PMID- 25956386
TI  - Development of the care programme for the last days of life for older patients in
      acute geriatric hospital wards: a phase 0-1 study according to the Medical
      Research Council Framework.
AB  - BACKGROUND: The effects of the Liverpool Care Pathway (LCP) have never been
      investigated in older patients dying in acute geriatric hospital wards and its
      content and implementation have never been adapted to this specific setting.
      Moreover, the LCP has recently been phased out in the UK hospitals. For that
      reason, this study aims to develop a new care programme to improve care in the
      last days of life for older patients dying in acute geriatric wards. METHODS: We
      conducted a phase 0-1 study according to the Medical Research Council Framework.
      Phase 0 consisted of a review of existing LCP programmes from the UK, Italy, and
      the Netherlands, a literature review to identify key factors for a successful LCP
      implementation and an analysis of the concerns raised in the UK. In phase 1, we
      developed a care programme for the last days of life for older patients dying in
      acute geriatric wards based on the results of phase 0. The care programme was
      reviewed and refined by two nurses and two physicians working in an acute
      geriatric ward and by two experts from Italy and the Netherlands. RESULTS: Phase
      0 resulted in the identification of nine important components within the LCP
      programmes, five key factors for a successful LCP implementation and a summary of
      the LCP concerns raised in the UK. Based on these findings we developed a new
      care programme consisting of (1) an adapted LCP document or Care Guide for the
      older patients dying in an acute geriatric ward, (2) supportive documentation,
      and (3) an implementation guide to assist health care staff in implementing the
      care programme on the acute geriatric ward. CONCLUSIONS: Based on the existing
      LCP programmes and taking into account the key factors for successful LCP
      implementation as well as the concerns raised in the UK, we developed a care
      programme for the last days of life and modelled it to the acute geriatric
      hospital wards after gaining feedback from health professionals caring for older
      hospitalized patients.

PMID- 25956385
TI  - The CSAW Study (Can Shoulder Arthroscopy Work?) - a placebo-controlled surgical
      intervention trial assessing the clinical and cost effectiveness of arthroscopic
      subacromial decompression for shoulder pain: study protocol for a randomised
      controlled trial.
AB  - BACKGROUND: Arthroscopic subacromial decompression (ASAD) is a commonly performed
      surgical intervention for shoulder pain. The rationale is that removal of a bony
      acromial spur relieves symptoms by decompressing rotator cuff tendons passing
      through the subacromial space. However, the efficacy of this procedure is
      uncertain. The objective of this trial was to compare the efficacy and cost
      effectiveness of ASAD in patients with subacromial pain using appropriate control
      groups, including placebo intervention. METHODS/DESIGN: The trial is a three
      group, parallel design, pragmatic, randomised controlled study. The intervention
      content for each group (ASAD, active monitoring with specialist reassessment
      (AMSR) and investigational shoulder arthroscopy only (AO)) enables assessment of
      (1) the efficacy of the surgery against no surgery; (2) the need for a specific
      component of the surgery-namely, removal of the bony spur; and (3) quantification
      of the placebo effect. Concealed allocation was performed using a 1:1:1
      randomisation ratio and using age, sex, baseline Oxford Shoulder Score (OSS) and
      centre as minimisation criteria. The primary outcome measure is the OSS at 6
      months post randomisation. A total of 300 patients recruited over 24 months from
      a minimum of 14 UK shoulder units over 24 months were required to detect a
      difference of 4.5 points on the OSS (standard deviation, 9) with 90% power and to
      allow for 15% loss to follow-up. Secondary outcomes include cost-effectiveness,
      pain, complications and patient satisfaction. A substantial qualitative research
      component is included. The primary analysis will be conducted on the modified
      intention-to-treat analysis. Sensitivity analysis will be used to assess the
      robustness of the results with regard to the underlying assumptions about missing
      data using multiple imputation. DISCUSSION: This trial uses an innovative design
      to account for the known placebo effects of surgery, but it also will delineate
      the mechanism for any benefit from surgery. The investigational AO group is
      considered a placebo intervention (not sham surgery), as it includes all
      components of subacromial decompression except the critical surgical element.
      Some discussion is also dedicated to the challenges of conducting placebo surgery
      trials. TRIAL REGISTRATIONS: UK Clinical Research Network UKCRN12104. Registered
      22 May 2012. International Standard Randomised Controlled Trial ISRCTN33864128 .
      Registered 22 June 2012. ClinicalTrials.gov NCT01623011 . Registered 15 June
      2012.

PMID- 25956388
TI  - Lung cancer and metastasis: new opportunities and challenges.
AB  - Lung cancer continues to attract special attention since the real number of lung
      cancer mortality and incidence in 2014 was definitely higher than those estimated
      numbers according to the report from World Health Organization. The present
      special issue highly focuses on advanced discovery and development of lung cancer
      and metastasis and discusses about potential opportunities and challenges to be
      faced. The present issue explores clinical applications of cancer
      immunotherapies, gene therapies, radiotherapies, or target-oriented therapies. A
      new and novel methodology can be used to identify differential interactions of
      driver genes, cancer-predictive genes, subtype-specific genes, or disease
      exclusive genes or gene pairs from imbalanced or heterogeneous datasets. We also
      demonstrate the importance of lung cancer-specific gene mutations, epigenetics,
      gene sequencing, heterogeneity, or biomarker discovery. Clinical bioinformatics
      is emphasized as a critical tool and merging science. Novel therapies are
      designed and expected on basis of oncogenic molecular aberrations in lung cancer.

PMID- 25956387
TI  - Protocol for the detection and nutritional management of high-output stomas.
AB  - INTRODUCTION: An issue of recent research interest is excessive stoma output and
      its relation to electrolyte abnormalities. Some studies have identified this as a
      precursor of dehydration and renal dysfunction. A prospective study was performed
      of the complications associated with high-output stomas, to identify their
      causes, consequences and management. MATERIALS AND METHODS: This study was
      carried out by a multidisciplinary team of surgeons, gastroenterologists,
      nutritionists and hospital pharmacists. High-output stoma (HOS) was defined as
      output >=1500 ml for two consecutive days. The subjects included in the study
      population, 43 patients with a new permanent or temporary stoma, were classified
      according to the time of HOS onset as early HOS (<3 weeks after initial surgery)
      or late HOS (>=3 weeks after surgery). Circumstances permitting, a specific
      protocol for response to HOS was applied. Each patient was followed up until the
      fourth month after surgery. RESULTS: Early HOS was observed in 7 (16%) of the
      sample population of 43 hospital patients, and late HOS, in 6 of the 37 (16%) non
      early HOS population. By type of stoma, nearly all HOS cases affected ileostomy,
      rather than colostomy, patients. The patients with early HOS remained in hospital
      for 18 days post surgery, significantly longer than those with no HOS (12 days).
      The protocol was applied to the majority of EHOS patients and achieved 100%
      effectiveness. 50% of readmissions were due to altered electrolyte balance.
      Hypomagnesaemia was observed in 33% of the late HOS patients. CONCLUSION: The
      protocol developed at our hospital for the detection and management of HOS
      effectively addresses possible long-term complications arising from poor
      nutritional status and chronic electrolyte alteration.

PMID- 25956389
TI  - Bilateral congenital seudarthrosis of the clavicle. A clinical case.
AB  - Congenital pseudarthrosis of the clavicle is a rare malformation in which the
      aetiology is still unclear. Bilateral involvement is exceptional. Although it is
      a congenital malformation, it may not be diagnosed until late childhood, with
      patients presenting with a painless deformity of the middle third of the clavicle
      in the absence of prior trauma. The treatment is controversial, and may be
      surgical, depending on the functional impact and aesthetics. A case of bilateral
      involvement is presented, together with a review of the relevant literature.

PMID- 25956390
TI  - Occam's razor or Hickam's dictum: a rare case of pulmonary embolism after
      myocardial infarction and stroke from aortic arch thrombi.

PMID- 25956391
TI  - Ebola virus disease managed with blood product replacement and point of care
      tests in Sierra Leone.

PMID- 25956392
TI  - Acute hospital care: how much activity is attributable to caring for patients
      with dementia?
AB  - BACKGROUND: People with dementia are among the most frequent service users in the
      acute hospital. Despite this, the acute hospital is not organized in a manner
      that best addresses their needs. METHODS: We examined acute dementia care over a
      3-year period from 2010 to 2012 in a 600-bed university hospital, to clarify the
      service activity and costs attributable to acute dementia care. RESULTS: Nine
      hundred and twenty-nine patients with dementia were admitted during the study
      period, accounting for 1433/69 718 (2%) of all inpatient episodes, comprising 44
      449/454 169 (10%) of total bed days. The average length of stay was 31.0 days in
      the dementia group and 14.1 days in those >65 years without dementia. The average
      hospital care cost was almost three times more (?13 832) per patient with
      dementia, compared with (?5404) non-dementia patients, accounting for 5% (almost
      ?20 000 000) of the total hospital casemix budget for the period. DISCUSSION:
      Service activity attributable to dementia care in the acute hospital is
      considerable. Moreover, given the fact that a significant minority of cognitive
      impairment goes unrecognized after acute admissions, it is likely that this is
      under-representative of the full impact of dementia in acute care. Although the
      money currently being spent on acute dementia care is considerable, it is being
      used to provide a service that does not meet its user needs adequately. It is
      clear that acute hospitals need to provide a more 'dementia friendly' service for
      acutely unwell older persons.

PMID- 25956393
TI  - Verification of the reliability and validity of a Japanese version of the Quality
      of Life in Childhood Epilepsy Questionnaire (QOLCE-J).
AB  - OBJECTIVE: A Japanese version of the Quality of Life in Childhood Epilepsy
      Questionnaire (QOLCE-J) was developed using international guidelines as a QOL
      scale for childhood epilepsy; its reliability and validity were examined,
      focusing on Japanese pediatric epilepsy patients applicability. METHODS: A pilot
      test questionnaire survey was conducted; involving parents of pediatric epilepsy
      patients aged 4-15 undergoing outpatient treatment. 278 responses were obtained
      and analyzed. RESULTS: Internal consistency for the 16 QOLCE-J subscales, except
      for <depression>, was sufficient, and a high overall coefficient alpha was
      obtained. The intraclass correlation coefficient was also high, supporting the
      test-retest reliability of this version. Associations among the subscales, high
      correlations of r>0.7 were observed among <attention/concentration>, <memory>,
      and <language>, representing cognitive and behavioral aspects, and among these
      and <behavior>. In contrast, correlations among others were moderate or weaker.
      Furthermore, correlations of r>0.35 were observed among the subscales of the SDQ
      (Strength and Difficulties Questionnaire) used as an external criterion and the
      QOLCE-J, confirming the criterion validity of the study version. Analysis of
      associations between the total QOLCE-J score and pathology of epilepsy, found
      significant correlation with age of onset and frequency of seizures, ADL, and
      antiepileptics side effects' symptoms. QOLCE has mostly been used in treatment
      resistant pediatric patients, the influence of interictal period presently
      observed, like antiepileptic side effects' symptoms; suggest usefulness for
      pediatric patients with seizures under control. CONCLUSIONS: The QOLCE-J with
      sufficient reliability and validity may be applicable as a QOL scale for Japanese
      children with epilepsy.

PMID- 25956395
TI  - Oculomotor nerve palsy induced by internal carotid artery aneurysm: prognostic
      factors for recovery.
AB  - BACKGROUND: Aneurysms at the posterior face of the internal carotid artery can
      lead to oculomotor nerve palsy (ONP) with an uncertain prognosis of recovery post
      treatment. The aim of this study was to define the prognostic factors for ONP
      recovery, with particular interest in treatment modality (surgery or endovascular
      techniques). METHOD: A literature review was performed to select the most
      pertinent prognostic factors. A retrospective study was then performed to
      determine whether these factors had significantly modified the prognosis of ONP
      recovery in our series of patients. RESULTS: In the literature, factors linked to
      poorer outcome were age, vascular risk factors, initial ONP severity and delay
      before treatment; better recovery was associated with surgical treatment. Between
      2000 and 2013, 23 consecutive patients were treated in our department for ONP
      inducing aneurysms: 14 by endovascular embolization and 9 by surgical clipping
      and aneurysm puncture. Mean follow-up was 48.8 months. After treatment, overall
      recovery occurred in 87% of cases, always within 6 months. Apart from treatment
      modality, no selected prognostic factor significantly modified the quality or
      timing of ONP recovery. In the endovascular group, four patients recovered
      completely, seven partially and three did not recover. In the surgical group,
      seven patients recovered completely and two partially. Surgery was significantly
      associated with a more complete and earlier ONP recovery (p < 0.05). CONCLUSIONS:
      Surgery was associated with a more complete and earlier ONP recovery as compared
      to endovascular treatment, confirming the results of previous studies. However,
      conclusions must be confirmed by a prospective randomized study.

PMID- 25956394
TI  - Extended evaluation of a phase 1/2 trial on dosing, safety, immunogenicity, and
      overall survival after immunizations with an advanced-generation Ad5 [E1-, E2b-]
      CEA(6D) vaccine in late-stage colorectal cancer.
AB  - A phase 1/2 clinical trial evaluating dosing, safety, immunogenicity, and overall
      survival on metastatic colorectal cancer (mCRC) patients after immunotherapy with
      an advanced-generation Ad5 [E1-, E2b-]-CEA(6D) vaccine was performed. We report
      our extended observations on long-term overall survival and further immune
      analyses on a subset of treated patients including assessment of cytolytic T cell
      responses, T regulatory (Treg) to T effector (Teff) cell ratios, flow cytometry
      on peripheral blood mononuclear cells (PBMCs), and determination of HLA-A2
      status. An overall survival of 20 % (median survival 11 months) was observed
      during long-term follow-up, and no long-term adverse effects were reported.
      Cytolytic T cell responses increased after immunizations, and cell-mediated
      immune (CMI) responses were induced whether or not patients were HLA-A2 positive
      or Ad5 immune. PBMC samples from a small subset of patients were available for
      follow-up immune analyses. It was observed that the levels of carcinoembryonic
      antigen (CEA)-specific CMI activity decreased from their peak values during
      follow-up in five patients analyzed. Preliminary results revealed that activated
      CD4+ and CD8+ T cells were detected in a post-immunization sample exhibiting high
      CMI activity. Treg to Teff cell ratios were assessed, and samples from three of
      five patients exhibited a decrease in Treg to Teff cell ratio during the
      treatment protocol. Based upon the favorable safety and immunogenicity data
      obtained, we plan to perform an extensive immunologic and survival analysis on
      mCRC patients to be enrolled in a randomized/controlled clinical trial that
      investigates Ad5 [E1-, E2b-]-CEA(6D) as a single agent with booster
      immunizations.

PMID- 25956396
TI  - Unusual case of posterior fossa syndrome and bilateral hypertrophic olivary
      degeneration after surgical removal of a large fourth ventricle ependymoma in an
      adult.

PMID- 25956397
TI  - Endoscopic lavage for antibiotic unresponsive severe Acinetobacter baumanii
      ventriculitis: an unexplored treatment option.

PMID- 25956398
TI  - Oxime derivatives with larvicidal activity against Aedes aegypti L.
AB  - Oximes containing secondary metabolites constitute an important group of
      bioactive compounds and have been described and frequently updated in the
      literature due to their pharmacological properties. Thus, the aim of this study
      was to evaluate the larvicidal activity of a series of fourteen structurally
      related [1,4]-Benzoquinone mono-oximes on third-instar Aedes aegypti larvae and
      to investigate structure-activity relationships (SAR) of these compounds. Results
      of larvicidal assay revealed that all oximes were found to have larvicidal
      activity. Compound 2,6-dimethyl-[1,4]-benzoquinone oxime tosylate (11) was the
      most bioactive (LC50 = 9.858 ppm), followed by 2-methyl-[1,4]-benzoquinone oxime
      tosylate (9) (LC50 = 14.450 ppm). [1,4]-benzoquinone oxime (1) exhibited the
      lowest potency, with an LC50 = 121.181 ppm. The molecular characteristics which
      may help to understand the assayed compounds larvicidal activity were identified.
      SAR indicates that the addition of alkyl groups attached to the ring, number,
      position in the unsaturated cyclic structure, and size of these groups influence
      the larvicidal activity. Moreover, the lipophilicity seems to play an important
      role in increasing the larvicidal effect, because, in general, tosyl-containing
      products were more potent than products containing free OH.

PMID- 25956399
TI  - Identification and characterization of a microneme protein (NcMIC6) in Neospora
      caninum.
AB  - Neospora caninum, an Apicomplexa parasite, is the causative agent of neosporosis.
      As described for other members of Apicomplexa, microneme proteins (MICs) play a
      key role in attachment and invasion of host cells by N. caninum. Herein we
      identified N. caninum microneme protein 6 (NcMIC6) that is orthologous to
      Toxoplasma gondii microneme protein 6 (TgMIC6). The open reading frame of the
      NcMIC6 gene is 984 bp and encodes a 327 amino acid peptide. Sequence analysis
      showed that NcMIC6 included a signal peptide, a transmembrane region, three
      epidermal growth factor-like (EGF) domains, and two low complexity regions.
      Antibodies raised against recombinant NcMIC6 recognized an approximately 35-kDa
      native MIC6 protein in Western blots of N. caninum tachyzoites.
      Immunofluorescence analysis showed that NcMIC6 had a polar labeling pattern,
      which was consistent with localization of micronemes in the apical region. Pulse
      invasion assays showed that NcMIC6 translocated from the apical tip to the
      posterior end of the parasites. Secretion assays demonstrated that NcMIC6 was
      released into the supernatants. Importantly, it was clearly revealed by co
      immunoprecipitation that NcMIC6 formed a complex with other two soluble microneme
      proteins (NcMIC1 and NcMIC4). In conclusion, identification and characterization
      of the novel microneme protein NcMIC6 may contribute to understanding how this
      protein functions during the parasite motility and host cell invasion.

PMID- 25956400
TI  - First record of Chilodonella piscicola (Ciliophora: Chilodonellidae) from two
      endangered fishes, Schizothorax o'connori and Oxygymnocypris stewartii in Tibet.
AB  - Schizothorax o'connori and Oxygymnocypris stewartii are two endangered endemic
      Tibetan fishes that thrive in the Lhasa River at an average altitude over 4000 m.
      During artificial reproduction of endemic Tibetan fishes, the juvenile fish of S.
      o'connori and O. stewartii experienced mass mortality event. The causative agent
      is diagnosed to be a ciliate parasite, Chilodonella piscicola (syn. C. cyprini),
      which is common in various fishes. Here, we supplemented its description based on
      the morphological and molecular data. The body of C. piscicola is oval, 30-60 *
      25-40 MUm in vivo. Cyrtos is hook-like, composed of 9-10 toothed nematodesmal
      rods. Somatic kineties usually contain seven right kineties and nine left
      kineties. Two parallel circumoral kineties revolve round the cyrtos, and one
      preoral kinety extends to the anterior end of the fourth left-most kinety.
      Terminal fragment kinety is linear and on the top left of dorsal side. Sequence
      alignments revealed that the present SSU rDNA and ITS1-5.8S-ITS2 sequences are
      both most similar to the sequences of C. uncinata with the similarities of 98.2
      and 99.5%. The phylogenetic analyses showed that C. piscicola is sister to other
      Chilodonella species, whereas C. cyprini (FJ873805) cluster with Tetrahymena
      species. Molecular analysis shows that the ITS1-5.8S-ITS2 sequence of C. cyprini
      in GenBank is unreliable. Our study extended the host range of C. piscicola and
      supplemented and revised the molecular data. Besides, as far as we know, this is
      the first record of C. piscicola in Tibetan plateau.

PMID- 25956401
TI  - Ischemic Conditioning Is Safe and Effective for Octo- and Nonagenarians in Stroke
      Prevention and Treatment.
AB  - Symptomatic intracranial arterial stenosis (SIAS) is very common in octo- and
      nonagenarians, especially in the Chinese population, and is likely the most
      common cause of stroke recurrence worldwide. Clinical trials demonstrate that
      endovascular treatment, such as stenting, may not be suitable for octogenarians
      with systemic diseases. Hence, less invasive methods for the octogenarian
      patients are urgently needed. Our previous study (unique identifier: NCT01321749)
      showed that repetitive bilateral arm ischemic preconditioning (BAIPC) reduced the
      incidence of stroke recurrence by improving cerebral perfusion (confirmed by
      single photon emission computed tomography and transcranial Doppler sonography)
      in patients younger than 80 years of age; however, the safety and effectiveness
      of BAIPC on stroke prevention in octo- and nonagenarians with SIAS are still
      unclear. The objective of this study was to evaluate the safety and effectiveness
      of BAIPC in reducing stroke recurrence in octo- and nonagenarian patients with
      SIAS. Fifty-eight patients with SIAS were enrolled in this randomized controlled
      prospective study for 180 consecutive days. All patients enrolled in the study
      received standard medical management. Patients in the BAIPC group (n = 30)
      underwent 5 cycles consisting of bilateral arm ischemia followed by reperfusion
      for 5 min each twice daily. Those in the control group (n = 28) underwent sham
      BAIPC twice daily. Blood pressure, heart rate, local skin status, plasma
      myoglobin, and plasma levels of thrombotic and inflammatory markers were
      documented in both groups before beginning the study and for the first 30 days.
      Finally, the incidences of stroke recurrence and magnetic resonance imaging
      during the 180 days of treatment were compared. Compared with the control, BAIPC
      had no adverse effects on blood pressure, heart rate, local skin integrity, or
      plasma myoglobin, and did not induce cerebral hemorrhage in the studied cohort.
      BAIPC reduced plasma high sensitive C-reactive protein, interleukin-6,
      plasminogen activator inhibitor-1, leukocyte count, and platelet aggregation rate
      and elevated plasma tissue plasminogen activator (all p < 0.01). In 180 days, 2
      infarctions and 7 transient ischemic attacks were observed in the BAIPC group
      compared with 8 infarctions and 11 transient ischemic attacks in the sham BAIPC
      group (p < 0.05). BAIPC may safely inhibit stroke recurrence, protect against
      brain ischemia, and ameliorate plasma biomarkers of inflammation and coagulation
      in octo- and nonagenarians with SIAS. A multicenter trial is ongoing. CLINICAL
      TRIAL REGISTRATION: www.clinicaltrials.gov, unique identifier: NCT01570231.

PMID- 25956402
TI  - Satisfaction with information and unmet information needs in men and women with
      cancer.
AB  - PURPOSE: Information needs in cancer patients are high but often not fulfilled.
      This study aimed to examine the level of perceived information, information
      satisfaction, and unmet needs in a large sample of cancer patients. Further, we
      explored associations with emotional distress and quality of life accounting for
      gender. METHODS: In a multicenter, cross-sectional study in Germany, 4020 cancer
      patients (mean age 58 years, 51 % women) were evaluated. We obtained self-reports
      of information level, information satisfaction, and unmet needs, measured
      depressive symptoms with the Patient Health Questionnaire (PHQ-9), symptoms of
      anxiety with the Generalized Anxiety Disorder Scale (GAD-7), and health-related
      quality of life with the European Organisation for Research and Treatment of
      Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). RESULTS: Seventy
      two to 88 % of participants reported to be well informed regarding various
      aspects of their disease, except of psychological support (38 %). However, unmet
      information needs were also prevalent in 36 to 48 %. Gender differences found
      were generally small. Although men felt less informed about psychological
      support, they expressed fewer needs for further information regarding this topic.
      Irrespective of gender, patients who were less satisfied with information
      received and had more unmet needs reported more anxiety, depression, and lower
      quality of life. Up to three quarters of those classified as most severely
      distressed reported unmet needs for information about psychological support.
      CONCLUSIONS: In this largest study to date, we found high levels of both
      information received and satisfaction with information, but also considerable
      amounts of unmet needs, particularly regarding psychological support.
      IMPLICATIONS FOR CANCER SURVIVORS: Provision of information about psychosocial
      support seems important to increase utilization of support offers among
      distressed cancer survivors.

PMID- 25956403
TI  - beta3-Adrenoceptor-mediated relaxation of rat and human urinary bladder: roles of
      BKCa channels and Rho kinase.
AB  - Previous studies suggest that the large-conductance Ca(2+)-activated K(+) (BKCa)
      channel and Rho-kinase play major roles in the control of urinary bladder tone.
      Here, we investigated their involvement in beta-adrenoceptor (AR)-mediated
      relaxation of rat and human bladder. Concentration-response curves of
      isoprenaline and mirabegron-induced bladder relaxation were generated against
      passive tension and KCl- and carbachol-induced tone, in the absence or presence
      of the BKCa channel inhibitor iberiotoxin (100 nM) or the Rho-kinase inhibitor
      Y27,632 (1 MUM). Myosin light chain (MLC) phosphorylation was studied by Western
      blot. In rat, iberiotoxin only slightly altered isoprenaline- and mirabegron
      induced relaxation against KCl-induced tone but attenuated relaxation by both
      agonists against carbachol-induced tone. Y27,632 enhanced isoprenaline- or
      mirabegron-induced relaxation only against carbachol-induced tone. In humans,
      iberiotoxin slightly enhanced relaxation by both agonists against carbachol
      induced pre-contraction. Y27,632 did not change isoprenaline-induced relaxation
      but enhanced that by mirabegron. Under passive tension, MLC phosphorylation was
      markedly reduced by both beta-AR agonists, an effect insensitive to Y27,632. In
      the presence of carbachol, both beta-AR agonists increased MLC phosphorylation,
      an effect reduced by Y27,632 only in the presence of 1 MUM carbachol. These
      results indicate that the extent of BKCa channel and Rho-kinase involvement in
      relaxation induced by beta-AR agonists depends on pre contractile stimulus and
      species. 

PMID- 25956404
TI  - Adjuvant Transarterial Chemoembolization Following Liver Resection for
      Intrahepatic Cholangiocarcinoma Based on Survival Risk Stratification.
AB  - BACKGROUND: The effectiveness of adjuvant transarterial chemoembolization (TACE)
      for intrahepatic cholangiocarcinoma (ICC) after hepatectomy remains unclear. This
      study was performed to identify ICC patients who would benefit from adjuvant
      TACE. PATIENTS AND METHODS: The study included 553 patients who underwent
      hepatectomy for ICC between January 2008 and February 2011 at the Eastern
      Hepatobiliary Surgery Hospital and who were treated with or without TACE (122
      with TACE and 431 without TACE). Survival risk stratification was performed using
      the established prognostic nomogram (ICC nomogram). The predictive performance
      was evaluated by concordance index and calibration. The tumor recurrence and
      overall survival (OS) rates were analyzed by the Kaplan-Meier method before and
      after propensity score matching (PSM). RESULTS: The predictive performance of the
      ICC nomogram was demonstrated by the well-fitted calibration curves and an
      optimal c-index of 0.71 for OS prediction. In the whole cohort, the 5-year
      recurrence and OS rates between the TACE and non-TACE groups were significantly
      different (5-year recurrence: 72.9% vs. 78.1%; OS: 38.4% vs. 29.7%). After 1:1
      PSM, the TACE and non-TACE groups (122 patients each) had similar 5-year
      recurrence and OS rates (5-year recurrence: 72.9% vs. 74.2%; OS: 38.4% vs.
      36.0%). By survival risk stratification based on ICC nomogram, only the patients
      in the lowest tertile (nomogram scores >=77) benefited from adjuvant TACE (TACE
      vs. non-TACE groups: 90.4% vs. 95.9% for 5-year recurrence; 21.3% vs. 6.2% for 5
      year OS). CONCLUSION: Adjuvant TACE following liver resection might be suitable
      for ICC patients with high ICC nomogram scores (>=77). IMPLICATIONS FOR PRACTICE:
      The accurate predictive performance of the established prognostic nomogram for
      intrahepatic cholangiocarcinoma (ICC) following liver resection was reconfirmed
      in an independent cohort with 553 patients. Based on the survival risk
      stratification using the nomogram, adjuvant transarterial chemoembolization
      following liver resection might be suitable only for ICC patients with high
      scores from the nomogram.

PMID- 25956406
TI  - "How Long Do I Have?"-Story of a Myeloma Patient.

PMID- 25956405
TI  - A Retrospective Evaluation of Vemurafenib as Treatment for BRAF-Mutant Melanoma
      Brain Metastases.
AB  - BACKGROUND: RAF inhibitors are an effective therapy for patients with BRAF-mutant
      melanoma and brain metastasis. Efficacy data are derived from clinical studies
      enriched with physiologically fit patients; therefore, it is of interest to
      assess the real-world experience of vemurafenib in this population. Tumor
      specific genetic variants that influence sensitivity to RAF kinase inhibitors
      also require investigation. METHODS: Records of patients with BRAF-mutant
      melanoma and brain metastases who were treated with vemurafenib were reviewed.
      Clinical data were extracted to determine extracranial and intracranial objective
      response rates, progression-free survival (PFS), overall survival (OS), and
      safety. A bait-capture, next-generation sequencing assay was used to identify
      mutations in pretreatment tumors that could explain primary resistance to
      vemurafenib. RESULTS: Among patients with intracranial disease treated with
      vemurafenib, 27 were included in survival analyses and 22 patients were
      assessable for response. The extracranial and intracranial objective response
      rates were 71% and 50%, respectively. Discordant responses were observed between
      extracranial and intracranial metastatic sites in 4 of 19 evaluable patients.
      Median PFS was 4.1 months (95% confidence interval [CI]: 2.6-7.9); median
      intracranial PFS was 4.6 months (95% CI: 2.7-7.9), median OS was 7.5 months (95%
      CI: 4.3-not reached), with a 30.4% 1-year OS rate. Outcomes were influenced by
      performance status. Vemurafenib was tolerable, although radiation-induced
      dermatitis occurred in some patients who received whole-brain radiotherapy.
      Adequate samples for next-generation sequencing analysis were available for seven
      patients. Melanomas categorized as "poorly sensitive" (>=20% tumor growth, new
      lesions, or <=50% shrinkage for <4 months) harbored co-occurring mutations in
      genes predicted to activate the phosphatidylinositol 3-kinase-AKT (PI3K-AKT)
      pathway. CONCLUSION: Vemurafenib is highly active in BRAF-mutant melanoma brain
      metastases but has limited activity in patients with poor performance status. The
      safety and efficacy of concurrent radiotherapy and RAF inhibition requires
      careful clinical evaluation. Combination strategies blocking the MAPK and PI3K
      AKT pathway may be warranted in a subset of patients. IMPLICATIONS FOR PRACTICE:
      Vemurafenib is active for BRAF-mutant intracranial melanoma metastases in an
      unselected patient population typical of routine oncologic practice. Patients
      with poor performance status appear to have poor outcomes despite vemurafenib
      therapy. Preliminary data indicate that co-occurring or secondary alterations in
      the phosphatidylinositol 3-kinase-AKT (PI3K-AKT) pathway are involved in
      resistance to RAF inhibition, thus providing a rationale for dual MAPK and PI3K
      AKT pathway inhibition in this patient population.

PMID- 25956407
TI  - Cervical Cancer Screening Among Adult Women in China, 2010.
AB  - INTRODUCTION: Cervical cancer is one of the most commonly diagnosed cancers among
      women in China. The World Health Organization (WHO) recommends routine screening
      for cervical cancer, and the WHO Global Monitoring Framework suggests that every
      nation monitors cervical cancer screening. However, little information is
      available on cervical cancer screening behavior among women in China. METHODS: We
      used data from the 2010 China Chronic Disease and Risk Factor Surveillance System
      that included 51,989 women aged 18 years and older. We report the proportion of
      women who reported ever having had a Papanicolaou (Pap) test, stratified by
      sociodemographic characteristics and geographic region. Multivariable logistic
      regression modeling was performed to adjust for potential confounders. RESULTS:
      Overall, 21% of 51,989 women reported having ever had a Pap test. The highest
      proportion was reported among women aged 30-39 years (30.1%, 95% confidence
      interval, 26.8%-33.4%). In all geographic regions, women in rural areas were
      consistently less likely than women in urban areas to report having had a Pap
      test. Among women who reported ever having a Pap test, 82% reported having the
      most recent test in the past 3 years. Factors associated with reporting ever
      having a test were being aged 30-49 years, higher education, being married, and
      having urban health insurance. CONCLUSION: Our results indicate that screening
      programs need to be strengthened along with a more intense focus on specific
      demographic groups. National cervical cancer screening guidelines and
      comprehensive implementation strategies are needed to make screening services
      available and accessible to all women. IMPLICATIONS FOR PRACTICE: This study is
      the largest nationwide and population-based assessment of self-reported history
      of Pap test for cervical cancer screening in China. This article describes
      cervical cancer screening behavior among women and examines key demographic and
      geographic factors. Only one fifth of Chinese women reported having ever had a
      Pap test for cervical cancer screening. The results highlight the urgent need to
      develop national cervical cancer screening guidelines and strategies that make
      screening services widely available, accessible, and acceptable to all women,
      especially to those who reside in rural areas and those with no health insurance.

PMID- 25956408
TI  - Capillaries in the olfactory bulb but not the cortex are highly susceptible to
      virus-induced vascular leak and promote viral neuroinvasion.
AB  - Viral neuroinvasion is a critical step in the pathogenesis of viral encephalitis.
      Multiple mechanisms of neuroinvasion have been identified, but their relative
      contribution to central nervous system (CNS) infection remains unclear for many
      viruses. In this study, we examined neuroinvasion of the mosquito-borne
      bunyavirus La Crosse (LACV), the leading cause of pediatric viral encephalitis in
      the USA. We found that the olfactory bulb (OB) and tract were the initial areas
      of CNS virus infection in mice. Removal of the OB reduced the incidence of LACV
      induced disease demonstrating the importance of this area to neuroinvasion.
      However, we determined that infection of the OB was not due to axonal transport
      of virus from olfactory sensory neurons as ablation of these cells did not affect
      viral pathogenesis. Instead, we found that OB capillaries were compromised
      allowing leakage of virus-sized particles into the brain. Analysis of OB
      capillaries demonstrated specific alterations in cytoskeletal and Rho GTPase
      protein expression not observed in capillaries from other brain areas such as the
      cortex where leakage did not occur. Collectively, these findings indicate that
      LACV neuroinvasion occurs through hematogenous spread in specific brain regions
      where capillaries are prone to virus-induced activation such as the OB.
      Capillaries in these areas may be "hot spots" that are more susceptible to
      neuroinvasion not only for LACV, but other neurovirulent viruses as well.

PMID- 25956409
TI  - Microglia inflict delayed brain injury after subarachnoid hemorrhage.
AB  - Inflammatory changes have been postulated to contribute to secondary brain injury
      after aneurysmal subarachnoid hemorrhage (SAH). In human specimens after SAH as
      well as in experimental SAH using mice, we show an intracerebral accumulation of
      inflammatory cells between days 4 and 28 after the bleeding. Using bone marrow
      chimeric mice allowing tracing of all peripherally derived immune cells, we
      confirm a truly CNS-intrinsic, microglial origin of these immune cells,
      exhibiting an inflammatory state, and rule out invasion of myeloid cells from the
      periphery into the brain. Furthermore, we detect secondary neuro-axonal injury
      throughout the time course of SAH. Since neuronal cell death and microglia
      accumulation follow a similar time course, we addressed whether the occurrence of
      activated microglia and neuro-axonal injury upon SAH are causally linked by
      depleting microglia in vivo. Given that the amount of neuronal cell death was
      significantly reduced after microglia depletion, we conclude that microglia
      accumulation inflicts secondary brain injury after SAH. 

PMID- 25956410
TI  - Antifibrinolytic drugs for acute traumatic injury.
AB  - BACKGROUND: Uncontrolled bleeding is an important cause of death in trauma
      victims. Antifibrinolytic treatment has been shown to reduce blood loss following
      surgery and may also be effective in reducing blood loss following trauma.
      OBJECTIVES: To assess the effect of antifibrinolytic drugs in patients with acute
      traumatic injury. SEARCH METHODS: We ran the most recent search in January 2015.
      We searched the Cochrane Injuries Group's Specialised Register, The Cochrane
      Library, Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed
      Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase Classic+Embase
      (OvidSP), PubMed and clinical trials registries. SELECTION CRITERIA: Randomised
      controlled trials of antifibrinolytic agents (aprotinin, tranexamic acid [TXA],
      epsilon-aminocaproic acid and aminomethylbenzoic acid) following acute traumatic
      injury. DATA COLLECTION AND ANALYSIS: From the results of the screened electronic
      searches, bibliographic searches, and contacts with experts, two authors
      independently selected trials meeting the inclusion criteria, and extracted data.
      One review author assessed the risk of bias for key domains.Outcome measures
      included: mortality at end of follow-up (all-cause); adverse events (specifically
      vascular occlusive events [myocardial infarction, stroke, deep vein thrombosis or
      pulmonary embolism] and renal failure); number of patients undergoing surgical
      intervention or receiving blood transfusion; volume of blood transfused; volume
      of intracranial bleeding; brain ischaemic lesions; death or disability.We rated
      the quality of the evidence as 'high', 'moderate', 'low' or 'very low' according
      to the GRADE approach. MAIN RESULTS: Three trials met the inclusion criteria.Two
      trials (n = 20,451) assessed the effect of TXA. The larger of these (CRASH-2, n =
      20,211) was conducted in 40 countries and included patients with a variety of
      types of trauma; the other (n = 240) restricted itself to those with traumatic
      brain injury (TBI) only.One trial (n = 77) assessed aprotinin in participants
      with major bony trauma and shock.The pooled data show that antifibrinolytic drugs
      reduce the risk of death from any cause by 10% (RR 0.90, 95% CI 0.85 to 0.96; P =
      0.002) (quality of evidence: high). This estimate is based primarily on data from
      the CRASH-2 trial of TXA, which contributed 99% of the data.There is no evidence
      that antifibrinolytics have an effect on the risk of vascular occlusive events
      (quality of evidence: moderate), need for surgical intervention or receipt of
      blood transfusion (quality of evidence: high). There is no evidence for a
      difference in the effect by type of antifibrinolytic (TXA versus aprotinin)
      however, as the pooled analyses were based predominantly on trial data concerning
      the effects of TXA, the results can only be confidently applied to the effects of
      TXA. The effects of aprotinin in this patient group remain uncertain.There is
      some evidence from pooling data from one study (n = 240) and a subset of data
      from CRASH-2 (n = 270) in patients with TBI which suggest that TXA may reduce
      mortality although the estimates are imprecise, the quality of evidence is low,
      and uncertainty remains. Stronger evidence exists for the possibility of TXA
      reducing intracranial bleeding in this population. AUTHORS' CONCLUSIONS: TXA
      safely reduces mortality in trauma patients with bleeding without increasing the
      risk of adverse events.  TXA should be given as early as possible and within
      three hours of injury, as further analysis of the CRASH-2 trial showed that
      treatment later than this is unlikely to be effective and may be harmful.
      Although there is some promising evidence for the effect of TXA in patients with
      TBI, substantial uncertainty remains.Two ongoing trials being conducted in
      patients with isolated TBI should resolve these remaining uncertainties.

PMID- 25956411
TI  - The hybrid approach for palliation of hypoplastic left heart syndrome:
      Intermediate results of a single-center experience.
AB  - INTRODUCTION: Hypoplastic left heart syndrome (HLHS) is a major cause of cardiac
      death during the first week of life. The hybrid approach is a reliable,
      reproducible treatment option for patients with HLHS. Herein we report our
      results using this approach, focusing on its efficacy, safety and late outcome.
      METHODS: We reviewed prospectively collected data on patients treated for HLHS
      using a hybrid approach between July 2007 and September 2014. RESULTS: Nine
      patients had a stage 1 hybrid procedure, with seven undergoing a comprehensive
      stage 2 procedure. One patient completed the Fontan procedure. Five patients
      underwent balloon atrial septostomy after the hybrid procedure; in three
      patients, a stent was placed across the atrial septum. There were three deaths:
      two early after the hybrid procedure and one early after stage two palliation.
      Overall survival was 66%. CONCLUSIONS: In our single-center series, the hybrid
      approach for HLHS yields intermediate results comparable to those of the Norwood
      strategy. The existence of dedicated teams for the diagnosis and management of
      these patients, preferably in high-volume centers, is of major importance in this
      condition.

PMID- 25956412
TI  - Dual chamber permanent pacemaker implantation by femoral approach.

PMID- 25956413
TI  - Synthesis and evaluation of constrained phosphoramidate inhibitors of prostate
      specific membrane antigen.
AB  - Prostate-specific membrane antigen (PSMA) is a cell-surface enzyme-biomarker that
      is actively pursued for targeted delivery of imaging and therapeutic agents for
      prostate cancer. Our lab has developed PSMA inhibitors based on a phosphoramidate
      scaffold, which has shown both high selectivity for PSMA-positive tumors and
      rapid clearance in vivo when radiolabeled with (18)F. However, this scaffold
      exhibits hydrolytic instability under low pH and high temperature conditions,
      barring the use of other imaging or therapeutic radionuclides such as (68)Ga or
      (177)Lu. Previous studies in our lab have shown a trend in increasing acid
      stability as the distance between the phosphoramidate core and the alpha
      carboxylate of the P1 residue is increased. Therefore, a new generation of
      phosphoramidate inhibitors was developed based on trans-4-hydroxyproline as the
      P1 residue to restrict the interaction of the alpha-carboxylate to the
      phosphoramidate core. These hydroxyproline inhibitors demonstrated comparable
      IC50 values to earlier generations as well as enhanced thermal and acid
      stability. 

PMID- 25956414
TI  - Incorporation of an acyclic alkynyl nucleoside analog into siRNA improves
      silencing activity and nuclease resistance.
AB  - In order to improve the silencing activity and nuclease resistance of small
      interfering RNA (siRNA), we designed and synthesized an acyclic thymidine analog
      containing 4-pentyne-1,2-diol instead of d-ribofuranose. The incorporation of
      this analog into siRNAs at specific positions in the strands was found to enhance
      the silencing activity of siRNAs and to increase the resistance of the siRNA to
      hydrolytic degradation by a 3' exonuclease. 

PMID- 25956415
TI  - A fluorescent bisboronic acid compound that selectively labels cells expressing
      oligosaccharide Lewis X.
AB  - Two fluorescent diboronic acid compounds (6a and 6b) with a dipeptide linker were
      synthesized as potential sensors for cell surface saccharide Lewis X (Le(X)).
      Compound 6a with a dipeptide (H-Asp-Ala-) as the linker was found to selectively
      label CHOFUT4 cells, which express Le(x), at micromolar concentrations, while non
      Le(x)-expressing control cells were not labeled. 

PMID- 25956416
TI  - Design, synthesis and preliminary evaluation of (18)F-labelled 1,8-naphthyridin-
      and quinolin-2-one-3-carboxamide derivatives for PET imaging of CB2 cannabinoid
      receptor.
AB  - In the present work, we report the synthesis of new aryliodonium salts used as
      precursors of single-stage nucleophilic (18)F radiofluorination. The
      corresponding unlabelled fluorinated derivatives showed to be CB2 cannabinoid
      receptor specific ligands, with Ki values in the low nanomolar range and high
      CB2/CB1 selectivity. The radiolabelled compound [(18)F]CB91, was successfully
      formulated for in vivo administration, and its preliminary biodistribution was
      assessed with microPET/CT. This tracer presented a reasonable in vivo stability
      and a preferential extraction in the tissues that constitutionally express CB2
      cannabinoid receptor. The results obtained indicate [(18)F]CB91 as a possible
      candidate marker of CB2 cannabinoid receptor distribution. This study would open
      the way to further validation of this tracer for assessing pathologies for which
      the expression of this receptor is modified. 

PMID- 25956417
TI  - Effects of L-carnitine on follicular survival and graft function following
      autotransplantation of cryopreserved-thawed ovarian tissues.
AB  - The aim of this study was to investigate the effects of L-carnitine (LC) on
      follicular survival and ovarian function following cryopreservation-thawing and
      autotransplantation of ovarian tissues. ICR mice were divided into three groups:
      control; saline group (cryopreservation+autograft+saline); and LC group
      (cryopreservation+autograft+L-carnitine). The ovarian tissues from control group,
      saline group, and LC group were histological assessed. There were no significant
      differences in the percentage of morphologically normal primordial follicles
      between the LC group and the saline group. After 28 days of autotransplantation,
      apoptosis rates, plasma malondialdehyde (MDA), progesterone (P4) and estradiol
      (E2) concentrations, and follicular densities of grafts were evaluated. Apoptosis
      rate and the concentration of MDA in the LC group were significantly lower than
      those in the saline group. The concentration of E2 and follicular densities of
      grafts in LC group were significantly higher than that in saline group. LC
      inhibits follicle apoptosis and increases follicular survival and function of
      ovarian graft.

PMID- 25956418
TI  - Detection of 5-fluorouracil surface contamination in near real time.
AB  - OBJECTIVES: Contamination of workplace surfaces by antineoplastic drugs presents
      an exposure risk for healthcare workers. Traditional instrumental methods to
      detect contamination such as gas chromatography-mass spectrometry (GC-MS) or
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) are sensitive and
      accurate but expensive and incapable of producing results in real time. This
      limits their utility in preventing worker exposure. We are currently developing
      monitors based on lateral flow immunoassay that can detect drug contamination in
      near real time. In this report, we describe the laboratory performance of a 5
      fluorouracil (5-FU) monitor. METHODS: The monitor was evaluated by spiking
      ceramic, vinyl, composite, stainless steel, and glass surfaces of 100 cm(2) area
      with 5-FU masses of 0, 5, 10, 25, 50, and 100 ng. The surface was sampled with a
      wetted cotton swab, the swab was extracted with buffer, and the resulting
      solution was applied to a lateral flow monitor. Two ways of evaluating the
      response of these monitors were used: an electronic method where a lateral flow
      reader was used for measuring line intensities, and a visual method where the
      intensity of the test line was visually compared to the control line. RESULTS:
      The 5-FU monitor is capable of detecting 10 ng/100 cm(2) (0.1 ng/cm(2)) using the
      electronic reader and 25 ng/100 cm(2) (0.25 ng/cm(2)) using the visual comparison
      method for the surfaces studied. The response of the monitors was compared to LC
      MS/MS results for the same samples for validation and there was good correlation
      of the two methods but some differences in absolute response, especially at
      higher spiking levels for the surface samples.

PMID- 25956419
TI  - Development of a combination antibiogram for Pseudomonas aeruginosa bacteremia in
      an oncology population.
AB  - PURPOSE: Development of a combination antibiogram to identify combinations of
      antibiotics that have the highest likelihood of attaining one active agent in the
      empiric management of presumed Pseudomonas aeruginosa bacteremia. METHODS:
      Patients with cancer and P. aeruginosa bacteremia from January 1 to December 31,
      2012 were included in this analysis. The primary outcome was identification of
      effective combinations of beta-lactam and non-betalactam agents. An effective
      combination was defined as one which achieved in-vitro activity to greater than
      or equal to 85% of isolates collected. Furthermore, the addition of the non-beta
      lactam agent was required to increase the in-vitro activity by at least 5% over
      beta-lactam monotherapy. Multiple secondary outcomes were evaluated. RESULTS: One
      hundred and twenty-three P. aeruginosa isolates were included from 99 patients.
      Single agent beta-lactam sensitivities ranged from 72.4 to 79.7%. Combination
      regimen sensitivities ranged from 73.5 to 96.7%. All combination regimens that
      included a beta-lactam plus an aminoglycoside were found to be effective per the
      study definition. Independent risk factors for MDR P. aeruginosa were receipt of
      intravenous (IV) antibiotics within 90 days and hospital length of stay (LOS)
      greater than or equal to five days. Increasing the number of antibiotics received
      was associated with a decrease in survival to hospital discharge. CONCLUSIONS:
      Effective combination regimens included all beta-lactam aminoglycoside regimens.
      Receipt of IV antibiotics within 90 days and hospital LOS greater than or equal
      to five days were independent risk factors for MDR isolates.

PMID- 25956420
TI  - Pazopanib- and bevacizumab-induced reversible heart failure in a patient with
      metastatic renal cell carcinoma: A case report.

PMID- 25956421
TI  - Fosaprepitant for the prevention of nausea and vomiting in patients receiving
      BEAM or high-dose melphalan before autologous hematopoietic stem cell transplant.
AB  - PURPOSE: To assess the impact of single-dose fosaprepitant on nausea and emesis
      after BEAM and high-dose melphalan conditioning regimens for autologous
      hematopoietic stem cell transplantation. METHODS: In a single-center cohort study
      patients receiving melphalan containing hematopoietic stem cell transplantation
      regimens who received a one-time dose of 150 mg IV fosaprepitant (n = 56) were
      compared to a historical control (n = 70). RESULTS: The primary endpoint of no
      emesis from melphalan administration through five days afterward was 80% for the
      fosaprepitant group versus 66% in the control group (p = 0.068). Addition of
      fosaprepitant demonstrated significant improvement in emetic episodes per patient
      during the entire assessment period (p = 0.011) and days 1-5 after melphalan (p =
      0.045). Fosaprepitant resulted in no substantial nausea during the entire
      assessment period in 37% of high-dose melphalan patients and 57% of BEAM
      patients. CONCLUSIONS: Further studies are suggested to investigate the optimal
      number and timing of doses of fosaprepitant in this setting.

PMID- 25956423
TI  - A collection of evidence for the impact of the economic recession on road
      fatalities in Great Britain.
AB  - There was a considerable reduction in the number of fatalities on British roads
      between 2007 and 2010. This substantial change led to debate as to the cause of
      the reduction. Multiple sources of information and evidence have been collated
      including STATS19 road accident data, population data, socio-demographic data,
      economic patterns, weather trends and traffic and vehicle data. Summary analyses
      of these data sources show a reduction in overall traffic, a large reduction in
      HGV traffic, a reduction in young male drivers, a reduction in speeding, and a
      reduction in drink driving during the recession period. All of these reductions
      can be associated with a reduction in fatal accidents and have led to the
      conclusion that the economic recession changed behaviours in such a way that
      fewer people were killed on the roads in Britain during this period. 

PMID- 25956422
TI  - Pegfilgrastim use and bone pain: a cohort study of community-based cancer
      patients.
AB  - PURPOSE: Bone pain is a common adverse effect of the granulocyte colony
      stimulating factors filgrastim and pegfilgrastim. However, the incidence of
      reported bone pain varies and therapies to mitigate this adverse effect are
      limited to case reports and one randomized controlled trial. The purpose of this
      study was to describe pegfilgrastim use, the incidence and treatment of bone
      pain, and rate of severe or febrile neutropenia among cancer patients receiving
      pegfilgrastim at a metropolitan, hospital-based, community cancer center.
      METHODS: This retrospective chart review included the first 100 adult oncology
      patients who received at least one dose of pegfilgrastim from 1 January 2012 to
      31 December 2012. Descriptive analyses were used to evaluate the primary and
      secondary outcomes. RESULTS: Of the identified cases, 69 cancer patients were
      evaluable. Most patients (74%) received pegfilgrastim for primary prophylaxis.
      Pegfilgrastim-associated bone pain occurred in 19% and loratadine was the most
      common medication used to treat it. Among the patients who received pegfilgrastim
      for primary prophylaxis, 8% were hospitalized for febrile neutropenia. Among
      those hospitalized for febrile neutropenia, 64% had not received pegfilgrastim
      for primary prophylaxis. CONCLUSIONS: Pegfilgrastim is commonly used for primary
      prophylaxis during the first cycle of chemotherapy. Hospitalizations for febrile
      neutropenia occurred most commonly among patients without primary prophylaxis.
      Pegfilgrastim-associated bone pain occurred in a similar percentage, as reported
      in randomized controlled trials but less than that reported by survey. Loratadine
      was the most commonly employed medication to mitigate this adverse effect.

PMID- 25956424
TI  - Herbal drugs against cardiovascular disease: traditional medicine and modern
      development.
AB  - Herbal products have been used as conventional medicines for thousands of years,
      particularly in Eastern countries. Thousands of clinical and experimental
      investigations have focused on the effects and mechanisms-of-action of herbal
      medicine in the treatment of cardiovascular diseases (CVDs). Considering the
      history of clinical practice and the great potentials of herb medicine and/or its
      ingredients, a review on this topic would be helpful. This article discusses
      possible effects of herbal remedies in the prevention and treatment of CVDs.
      Crucially, we also summarize some underlying pharmacological mechanisms for herb
      products in cardiovascular regulations, which might provide interesting
      information for further understanding the effects of herbal medicines, and boost
      the prospect of new herbal products against CVDs. 

PMID- 25956425
TI  - [Engagement of the German Society of Neuroradiology in the European Society of
      Neuroradiology and the Union Europeenne des Medecins Specialistes].

PMID- 25956426
TI  - Apoptosis in muscle-to-meat aging process: The omic witness.
AB  - Meat derives from a muscle that undergoes a great number of biochemical and
      physiological changes. The anoxic condition established from the moment of animal
      sacrifice forces muscle cells to a sort of reaction, resulting in methodical
      programmed cell death to avoid necrosis. The duality autophagy and/or apoptosis
      is at the center of the scientific debate about the biological processes driving
      the muscle to meat conversion. Here we report an omic time course overview
      carried on proteome, phosphoproteome and metabolome of Piedmontese longissimus
      thoracis muscle searching for clues helping us to extricate through the dilemma.
      The survey depicts a progressive physiological impairing and our evidences push
      towards the apoptotic behavior: the proteomic time course trend of annexin A2,
      RKIP, HSPB6, alphaB crystalline, adenylate kinase, DJ-1 and 31kDa actin fragment;
      the 0-1day increased phosphorylation of myosin 2 and synaptopodin and the
      metabolomic time course trend of key metabolic indicators, like GSH/GSSG ratio,
      taurine and nitrotyrosine. The employed techniques provide strong indications
      about the likely apoptotic behavior of aging meat in muscle-to-meat conversion
      process. BIOLOGICAL SIGNIFICANCE: Our work underlines compelling evidences of the
      apoptotic behavior of Piedmontese beef muscle cells undergoing the muscle-to-meat
      process, whereas no autophagic clues are inferred from this omic investigation.

PMID- 25956427
TI  - Understanding different facets of cardiovascular diseases based on model systems
      to human studies: a proteomic and metabolomic perspective.
AB  - Cardiovascular disease has remained as the largest cause of morbidity and
      mortality worldwide. From dissecting the disease aetiology to identifying
      prognostic markers for better management of the disease is still a challenge for
      researchers. In the post human genome sequencing era much of the thrust has been
      focussed towards application of advanced genomic tools along with evaluation of
      traditional risk factors. With the advancement of next generation proteomics and
      metabolomics approaches it has now become possible to understand the protein
      interaction network & metabolic rewiring which lead to the perturbations of the
      disease phenotype. Further, elucidating different post translational
      modifications using advanced mass spectrometry based methods have provided an
      impetus towards in depth understanding of the proteome. The past decade has
      observed a plethora of studies where proteomics has been applied successfully to
      identify potential prognostic and diagnostic markers as well as to understand the
      disease mechanisms for various types of cardiovascular diseases. In this review,
      we attempted to document relevant proteomics based studies that have been
      undertaken either to identify potential biomarkers or have elucidated newer
      mechanistic insights into understanding the patho-physiology of cardiovascular
      disease, primarily coronary artery disease, cardiomyopathy, and myocardial
      ischemia. We have also provided a perspective on the potential of proteomics in
      combating this deadly disease. BIOLOGICAL SIGNIFICANCE: This review has
      catalogued recent studies on proteomics and metabolomics involved in
      understanding several cardiovascular diseases (CVDs). A holistic systems biology
      based approach, of which proteomics and metabolomics are two very important
      components, would help in delineating various pathways associated with complex
      disorders like CVD. This would ultimately provide better mechanistic
      understanding of the disease biology leading to development of prognostic
      biomarkers. This article is part of a Special Issue entitled: Proteomics in
      India.

PMID- 25956428
TI  - Levels of asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase
      inhibitor, and risk of coronary artery disease: A meta-analysis based on 4713
      participants.
AB  - BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of
      endothelial nitric oxide synthase by competing with L-arginine. As a result, the
      expression of nitric oxide decreases and endothelial dysfunction occurs. Studies
      have evaluated the association between the serum ADMA level and risk of coronary
      artery disease. However, conflicting results have been obtained. METHODS: Pubmed,
      Web of Science, Embase, Ovid, Cochrane databases were searched to identify
      eligible studies published in English until December 2014. Association was
      assessed on the basis of weighted mean differences (WMD) with 95% confidence
      intervals (CIs). Publication bias was analysed using Begg's and Egger's tests.
      Sensitivity analysis was performed to evaluate result stability. RESULTS: A total
      of 16 case-control studies with 2939 patients and 1774 controls were included in
      the meta-analysis. Pooled result indicated that patients with coronary artery
      disease yielded a higher ADMA level than healthy controls (WMD: 0.248, 95% CI:
      0.156-0.340; p = 1.16 e-7). Sensitivity analysis suggested that our meta-analysis
      result was stable. Subgroup analysis found a similar pattern in patients with
      myocardial infarction (WMD: 0.397, 95% CI: 0.112-0.683; p = 0.0106), stable
      angina pectoris (WMD: 0.197, 95% CI: 0.031-0.364; p = 0.02) and unstable angina
      pectoris (WMD: 0.857, 95% CI: 0.293-1.420; p = 0.003). CONCLUSIONS: Meta-analysis
      results indicated that an increased ADMA level is associated with an increased
      risk of coronary artery disease.

PMID- 25956429
TI  - National Health Action Party beats Liberal Democrats in three seats and vows to
      fight on.

PMID- 25956430
TI  - Effects of pubertal timing on deviant behaviors in Taiwan: A longitudinal
      analysis of 7th- to 12th-grade adolescents.
AB  - We investigated the relationship between pubertal timing and deviant behaviors in
      Taiwan using Taiwan Youth Project (TYP) data. The TYP used multistage-stratified
      and class-clustered methods in 40 randomly selected schools. We analyzed 1541
      adolescents (770 boys; 50.0%) who self-reported their deviant behaviors in 7th,
      8th, 10th, and 12th grades. Participants were assigned to early- (n = 244;
      15.8%), on-time- (n = 992; 64.4%), and late- (n = 305; 19.8%) puberty groups, and
      one-way analysis of variance and latent growth modeling were used to examine the
      frequency of deviant behaviors between them. Early-puberty adolescents had more
      deviant behaviors (mean = 0.43, SD = 0.74) than did late-puberty adolescents
      during 7th grade (mean = 0.27, SD = 0.59; p = 0.004), but not after 8th grade.
      There were no significant differences in the deviance level between on-time
      puberty and early- and late-puberty adolescents. Moreover, puberty was not
      correlated with the growth of deviant behaviors, which decreased with age.
      However, boys seemed to engage in more deviant behaviors at the beginning, but
      their engagement seemed to decline faster than it did for girls. In sum, the
      deviance of early-puberty adolescents seemed to diminish as they got older. 

PMID- 25956431
TI  - Prognostic value of tumor suppressors in osteosarcoma before and after
      neoadjuvant chemotherapy.
AB  - BACKGROUND: Primary bone cancers are among the deadliest cancer types in
      adolescents, with osteosarcomas being the most prevalent form. Osteosarcomas are
      commonly treated with multi-drug neoadjuvant chemotherapy and therapy success as
      well as patient survival is affected by the presence of tumor suppressors. In
      order to assess the prognostic value of tumor-suppressive biomarkers, primary
      osteosarcoma tissues were analyzed prior to and after neoadjuvant chemotherapy.
      METHODS: We constructed a tissue microarray from high grade osteosarcoma samples,
      consisting of 48 chemotherapy naive biopsies (BXs) and 47 tumor resections (RXs)
      after neoadjuvant chemotherapy. We performed immunohistochemical stainings of
      P53, P16, maspin, PTEN, BMI1 and Ki67, characterized the subcellular localization
      and related staining outcome with chemotherapy response and overall survival.
      Binary logistic regression analysis was used to analyze chemotherapy response and
      Kaplan-Meier-analysis as well as the Cox proportional hazards model was applied
      for analysis of patient survival. RESULTS: No significant associations between
      biomarker expression in BXs and patient survival or chemotherapy response were
      detected. In univariate analysis, positive immunohistochemistry of P53 (P =
      0.008) and P16 (P16; P = 0.033) in RXs was significantly associated with poor
      survival prognosis. In addition, presence of P16 in RXs was associated with poor
      survival in multivariate regression analysis (P = 0.003; HR = 0.067) while
      absence of P16 was associated with good chemotherapy response (P = 0.004; OR =
      74.076). Presence of PTEN on tumor RXs was significantly associated with an
      improved survival prognosis (P = 0.022). CONCLUSIONS: Positive
      immunohistochemistry (IHC) of P16 and P53 in RXs was indicative for poor overall
      patient survival whereas positive IHC of PTEN was prognostic for good overall
      patient survival. In addition, we found that P16 might be a marker of
      osteosarcoma chemotherapy resistance. Therefore, our study supports the use of
      tumor RXs to assess the prognostic value of biomarkers.

PMID- 25956433
TI  - Elevation of cardiovascular risk by non-steroidal anti-inflammatory drugs.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most frequently
      used medications. NSAIDs profoundly modify prostaglandin homeostasis through
      inhibition of the enzyme, cyclooxygenase (COX), especially COX-2. COX-2
      inhibition is associated with adverse cardiovascular outcomes as demonstrated by
      recent trials using this type of drug. This review explores the latest available
      data, including recent, randomized, clinical trials, controversies, and
      pathophysiology of the adverse effects of COX-inhibition. 

PMID- 25956432
TI  - Adhesion G Protein-Coupled Receptors: From In Vitro Pharmacology to In Vivo
      Mechanisms.
AB  - The adhesion family of G protein-coupled receptors (aGPCRs) comprises 33 members
      in humans. aGPCRs are characterized by their enormous size and complex modular
      structures. While the physiologic importance of many aGPCRs has been clearly
      demonstrated in recent years, the underlying molecular functions have only
      recently begun to be elucidated. In this minireview, we present an overview of
      our current knowledge on aGPCR activation and signal transduction with a focus on
      the latest findings regarding the interplay between ligand binding, mechanical
      force, and the tethered agonistic Stachel sequence, as well as implications on
      translational approaches that may derive from understanding aGPCR pharmacology. 

PMID- 25956434
TI  - Temporal evolution on MRI of successful treatment of rabies.
AB  - Rabies is a nearly uniformly fatal disease for individuals who develop clinical
      symptoms. We report a case of a patient with paralytic rabies who survived after
      being treated with what is now known as Milwaukee protocol. This is only the
      third known case of rabies survival after being treated with the protocol. We
      present sequential magnetic resonance imaging (MRI) findings of the brain and
      lumbar spine throughout the course of her treatment. In doing so, we provide
      insight into the temporal evolution of MRI findings in the brain and lumbar
      spine. 

PMID- 25956435
TI  - GI hemorrhage arising from splenic artery: intraprocedure cone-beam CT as problem
      solving tool to aide in safe catheterization of offending vessel.
AB  - We present the case of a 67-year-old female with melena and hypotension who was
      found to have a bleeding splenic artery pseudoaneurysm subjacent to a large
      gastric ulcer on computed tomographic angiography. The lesion was
      angiographically occult on standard anteroposterior and oblique projections. The
      offending vessel was identified on intraprocedure cone-beam computed tomography
      (CT). This case illustrates the value of intraprocedure cone-beam CT as a problem
      solving tool for the interventional radiologist. 

PMID- 25956436
TI  - Differentiation of true-progression from pseudoprogression in glioblastoma
      treated with radiation therapy and concomitant temozolomide by GLCM texture
      analysis of conventional MRI.
AB  - Twenty-two patients with pathologically confirmed glioblastoma who had received
      concurrent CCRT with TMZ underwent conventional MRI including T1-weighted
      imaging(T1WI), T2-weighted imaging(T2WI), fluid attenuated inversion
      recovery(FLAIR)and contrast-enhanced T1WI(T1Ce). Five GLCM texture maps of
      contrast, energy, entropy, correlation and homogeneity were generated for each
      MRI series. Of the aforementioned 5 texture features, the most significant
      features were contrast and correlation on T2WI with areas under ROC curve of
      0.883 and 0.892, respectively, and they had the same sensitivity of 75%,
      specificity of 100%, accuracy of 86.4%, PPV of 100% and NPV of 76.9% in
      differentiation true progression from pseudoprogression. 

PMID- 25956437
TI  - The Marine Strategy Framework Directive and the ecosystem-based approach -
      pitfalls and solutions.
AB  - The European Marine Strategy Framework Directive aims at good environmental
      status (GES) in marine waters, following an ecosystem-based approach, focused on
      11 descriptors related to ecosystem features, human drivers and pressures.
      Furthermore, 29 subordinate criteria and 56 attributes are detailed in an EU
      Commission Decision. The analysis of the Decision and the associated operational
      indicators revealed ambiguity in the use of terms, such as indicator, impact and
      habitat and considerable overlap of indicators assigned to various descriptors
      and criteria. We suggest re-arrangement and elimination of redundant criteria and
      attributes avoiding double counting in the subsequent indicator synthesis, a
      clear distinction between pressure and state descriptors and addition of criteria
      on ecosystem services and functioning. Moreover, we suggest the precautionary
      principle should be followed for the management of pressures and an evidence
      based approach for monitoring state as well as reaching and maintaining GES. 

PMID- 25956438
TI  - Nearshore dynamics of artificial sand and oil agglomerates.
AB  - Weathered oil can mix with sediment to form heavier-than-water sand and oil
      agglomerates (SOAs) that can cause beach re-oiling for years after a spill. Few
      studies have focused on the physical dynamics of SOAs. In this study, artificial
      SOAs (aSOAs) were created and deployed in the nearshore, and shear stress-based
      mobility formulations were assessed to predict SOA response. Prediction
      sensitivity to uncertainty in hydrodynamic conditions and shear stress
      parameterizations were explored. Critical stress estimates accounting for large
      particle exposure in a mixed bed gave the best predictions of mobility under
      shoaling and breaking waves. In the surf zone, the 10-cm aSOA was immobile and
      began to bury in the seafloor while smaller size classes dispersed alongshore.
      aSOAs up to 5 cm in diameter were frequently mobilized in the swash zone. The
      uncertainty in predicting aSOA dynamics reflects a broader uncertainty in
      applying mobility and transport formulations to cm-sized particles.

PMID- 25956439
TI  - Scallop larvae hatcheries as source of bacteria carrying genes encoding for non
      enzymatic phenicol resistance.
AB  - The main aim of the study was to evaluate the role of scallop hatcheries as
      source of the floR and cmlA genes. A number of 133 and 121 florfenicol-resistant
      strains were isolated from scallop larval cultures prior to their transfer to
      seawater and from effluent samples from 2 commercial hatcheries and identified by
      16S rRNA gene sequence analysis, observing a predominance of the Pseudomonas,
      Pseudoalteromonas and Halomonas genera and exhibiting an important incidence of
      co-resistance to streptomycin, oxytetracycline and co-trimoxazole. A high
      percentage of strains from both hatcheries carried the floR gene (68.4% and 89.3%
      of strains), whereas a lower carriage of the cmlA gene was detected (27.1% and
      54.5% of strains). The high prevalence of floR-carrying bacteria in reared
      scallop larvae and hatchery effluents contributes to enrich the marine resistome
      in marine environments, prompting the need of a continuous surveillance of these
      genes in the mariculture environments. 

PMID- 25956440
TI  - Bio-indicator bacteria & environmental variables of the coastal zones: The
      example of the Gulluk Bay, Aegean Sea, Turkey.
AB  - In this study bio-indicator bacteria and environmental variable parameters were
      investigated in the coastal areas of the Gulluk Bay, Aegean Sea, Turkey. The
      seawater samples which were taken from surface (0-30cm) were tested regarding
      total and fecal coliform, streptococci and nutrients from May to February in 2012
      2013. The primary hydrographic parameters were recorded using multiparameter (YSI
      556) in situ at the sampling stations. The highest fecal pollution stress and
      indicator bacteria values were observed in the period between June and August.
      The finding showed that bacterial pollution sources of the study area, especially
      in the summer season, under the control of increasing anthropogenic activities.
      The finding showed that terrestrial pollution sources carry a potential risk for
      public and ecosystem health and the sustainable use of living sources.
      Precautions should be formulated and put into action immediately in order to
      protect the region from bacteriological risks. 

PMID- 25956441
TI  - Integrated environmental mapping and monitoring, a methodological approach to
      optimise knowledge gathering and sampling strategy.
AB  - New technology has led to new opportunities for a holistic environmental
      monitoring approach adjusted to purpose and object of interest. The proposed
      integrated environmental mapping and monitoring (IEMM) concept, presented in this
      paper, describes the different steps in such a system from mission of survey to
      selection of parameters, sensors, sensor platforms, data collection, data
      storage, analysis and to data interpretation for reliable decision making. The
      system is generic; it can be used by authorities, industry and academia and is
      useful for planning- and operational phases. In the planning process the
      systematic approach is also ideal to identify areas with gap of knowledge. The
      critical stages of the concept is discussed and exemplified by two case studies,
      one environmental mapping and one monitoring case. As an operational system, the
      IEMM concept can contribute to an optimised integrated environmental mapping and
      monitoring for knowledge generation as basis for decision making. 

PMID- 25956442
TI  - Efficient extraction and detection of aromatic toxicants from crude oil and tar
      balls using multiple cyclodextrin derivatives.
AB  - Herein we report the efficient extraction of aromatic analytes from crude oil and
      tar balls using multiple cyclodextrin derivatives. The known propensity of the
      cyclodextrins to bind hydrophobic guests in their hydrophobic interiors enhanced
      the extraction of aromatic analytes from the oil layer to the aqueous layer, with
      methyl-beta-cyclodextrin and beta-cyclodextrin providing the most significant
      enhancement in extraction efficiencies of aromatic toxicants (69% aromatic
      toxicants in aqueous layer in the presence of methyl-beta-cyclodextrin compared
      to 47% in cyclodextrin-free solution for tar ball oil extraction), and provide
      optimal tunability for developing efficient extraction systems. The cyclodextrin
      derivatives also promoted efficient energy transfer in the aqueous solutions,
      with up to 86% efficient energy transfer observed in the presence of gamma
      cyclodextrin compared to 50% in the absence of cyclodextrin for oil spill oil
      extraction. Together, this dual function extraction followed by detection system
      has potential in the development of environmental remediation systems. 

PMID- 25956443
TI  - Daily variations in pathogenic bacterial populations in a monsoon influenced
      tropical environment.
AB  - Changing climatic conditions have influenced the monsoon pattern in recent years.
      Variations in bacterial population in one such tropical environment were observed
      everyday over two years and point out intra and inter annual changes driven by
      the intensity of rainfall. Vibrio spp. were abundant during the monsoon and so
      were faecal coliforms. Vibrio alginolyticus were negatively influenced by
      nitrate, whereas, silicate and rainfall positively influenced Vibrio
      parahaemolyticus numbers. It is also known that pathogenic bacteria are
      associated with the plankton. Changes in the abundance of plankton, which are
      governed mainly by environmental changes, could be responsible for variation in
      pathogenic bacterial abundance during monsoon, other than the land runoff due to
      precipitation and influx of fresh water. 

PMID- 25956444
TI  - Integrated treatment of molasses distillery wastewater using microfiltration
      (MF).
AB  - To achieve zero-liquid discharge, high pressure reverse osmosis (RO) of effluent
      is being employed by molasses based alcohol distilleries. Low pressure and thus
      less energy intensive microfiltration (MF) is well established for particulate
      separation but is not suitable for removal of dissolved organics and color. This
      work investigates two schemes incorporating MF for molasses distillery wastewater
      (a) chemical coagulation followed by treatment in a membrane bioreactor (MBR)
      using MF and (b) electrocoagulation followed by MF. The performance was assessed
      in terms of COD and color reduction; the conversion of the generated sludge into
      a zeolite desiccant was also examined. A comparison of the schemes indicates
      electrocoagulation followed by MF through a 0.1 MUm membrane to be most
      effective. By hydrothermal treatment, electrocoagulated sludge can be transformed
      into a porous NaX zeolite with a surface area of 86 m(2)/g, which is comparable
      to commercial desiccants. 

PMID- 25956445
TI  - Determinants of Job Satisfaction and Turnover Intent in Home Health Workers: The
      Role of Job Demands and Resources.
AB  - Based on the job demands-resources (JD-R) model, this study explored the impact
      of job demands (physical injury and racial/ethnic discrimination) and resources
      (self-confidence in job performance and recognition by
      supervisor/organization/society) on home health workers' employee outcomes (job
      satisfaction and turnover intent). Using data from the National Home Health Aide
      Survey (N = 3,354), multivariate models of job satisfaction and turnover intent
      were explored. In both models, the negative impact of demands (physical injury
      and racial/ethnic discrimination) and the positive impact of resources (self
      confidence in job performance and recognition by supervisor and organization)
      were observed. The overall findings suggest that physical injury and
      discrimination should be prioritized in prevention and intervention efforts to
      improve home health workers' safety and well-being. Attention also needs to be
      paid to ways to bolster work-related efficacy and to promote an organizational
      culture of appreciation and respect.

PMID- 25956446
TI  - Clinician Perspectives on Challenges to Patient Centered Care at the End of Life.
AB  - Discussions regarding patient preferences for resuscitation are often delayed and
      preferences may be neglected, leading to the receipt of unwanted medical care. To
      better understand barriers to the expression and realization of patients' end of
      life wishes, a preventive ethics team in one Veterans Affairs Medical Center
      conducted a survey of physicians, nurses, social workers, and respiratory
      therapists. Surveys were analyzed through qualitative analysis, using sorting
      methodologies to identify themes. Analysis revealed barriers to patient wishes
      being identified and followed, including discomfort conducting end-of-life
      discussions, difficulty locating patients' preferences in medical records,
      challenges with expiring do not resuscitate (DNR) orders, and confusion over
      terminology. Based on these findings, the preventive ethics team proposed new
      terminology for code status preferences, elimination of the local policy for
      expiration of DNR orders, and enhanced systems for storing and retrieving
      patients' end-of-life preferences. Educational efforts were initiated to
      facilitate implementation of the proposed changes.

PMID- 25956447
TI  - The c.1364C>A (p.A455E) Mutation in the CFTR Pseudogene Results in an Incorrectly
      Assigned Carrier Status by a Commonly Used Screening Platform.
AB  - Cystic fibrosis (CF) is one of the most common recessive conditions among whites,
      with an estimated carrier frequency of 1 in 25 in the United States. Population
      based CF carrier screening was implemented in the United States in 2001. The
      number of mutations screened by each laboratory may vary; however, the 23 most
      common CF mutations recommended for screening by the American College of Medical
      Genetics and American College of Obstetricians and Gynecologists are included in
      all platforms. The c.1364C>A (p.A455E) mutation located in exon 10 of the CFTR
      gene is one of the 23 mutations. Because CFTR exon 10 and its flanking intronic
      regions are duplicated and transposed onto several other chromosomes of the human
      genome during evolution and function as unprocessed pseudogenes, variations in
      the CFTR pseudogenes may confound CF screening results for mutations located in
      exon 10 of the CFTR gene. We report an incorrectly identified carrier status for
      the c.1364C>A (p.A455E) mutation in a healthy individual using the Hologic InPlex
      CF assay. Further analysis revealed that the mutation resides in one of the CFTR
      pseudogenes. Because most commercial kits and laboratory-developed tests for CF
      carrier screening involve a short amplicon encompassing this mutation, this
      finding suggests that individuals with the c.1364C>A (p.A455E) mutation may
      require further investigation to avoid a false assignment of CF carrier status. 

PMID- 25956448
TI  - Evaluation of HER2 Gene Status in Breast Cancer Samples with Indeterminate
      Fluorescence in Situ Hybridization by Quantitative Real-Time PCR.
AB  - Administration of drugs targeting HER2 (official symbol ERBB2) is an important
      component of therapy for breast cancer patients with HER2
      amplification/overexpression as determined by in situ hybridization (ISH) and
      immunohistochemistry (IHC). In approximately 5% of breast cancers, ISH assays
      fail. In these cases, HER2 protein expression is evaluated by IHC alone that may
      yield false negatives/positives for poor-quality samples. Therefore, we developed
      a method that was based on quantitative real-time PCR applicable for DNA from
      formalin-fixed, paraffin-embedded tissue samples. Its limit of detection was
      determined with breast cancer cell lines and validated with 223 breast cancer
      patient samples. On the basis of comparisons with fluorescent ISH (FISH) and IHC
      data, the sensitivity of the new method was 94.2% and 95.1%, its specificity was
      100% and 99.1%, and overall concordance between results obtained with the
      quantitative real-time PCR method and FISH/IHC was 97.6% for both methods. The
      quantitative real-time PCR method was then used to evaluate the HER2 status of
      198 of 3696 breast cancer tissues that yielded indeterminate FISH results. The
      HER2 copy number was successfully determined in 69.2% of these indeterminate
      samples. Thus, the DNA-based technique appears to be a specific, sensitive method
      for determining HER2 copy numbers when the FISH assay fails, which may complement
      IHC tests. 

PMID- 25956449
TI  - Aromatic L-amino acid decarboxylase deficiency diagnosed by clinical metabolomic
      profiling of plasma.
AB  - Aromatic L-amino acid decarboxylase (AADC) deficiency is an inborn error of
      metabolism affecting the biosynthesis of serotonin, dopamine, and catecholamines.
      We report a case of AADC deficiency that was detected using the Global MAPS
      platform. This is a novel platform that allows for parallel clinical testing of
      hundreds of metabolites in a single plasma specimen. It uses a state-of-the-art
      mass spectrometry platform, and the resulting spectra are compared against a
      library of ~2500 metabolites. Our patient is now a 4 year old boy initially seen
      at 11 months of age for developmental delay and hypotonia. Multiple tests had not
      yielded a diagnosis until exome sequencing revealed compound heterozygous
      variants of uncertain significance (VUS), c.286G>A (p.G96R) and c.260C>T (p.P87L)
      in the DDC gene, causal for AADC deficiency. CSF neurotransmitter analysis
      confirmed the diagnosis with elevated 3-methoxytyrosine (3-O-methyldopa).
      Metabolomic profiling was performed on plasma and revealed marked elevation in 3
      methoxytyrosine (Z-score +6.1) consistent with the diagnosis of AADC deficiency.
      These results demonstrate that the Global MAPS platform is able to diagnose AADC
      deficiency from plasma. In summary, we report a novel and less invasive approach
      to diagnose AADC deficiency using plasma metabolomic profiling.

PMID- 25956450
TI  - Novel missense mutations in PNPLA2 causing late onset and clinical heterogeneity
      of neutral lipid storage disease with myopathy in three siblings.
AB  - Neutral lipid storage disease with myopathy (NLSD-M) is a rare autosomal
      recessive disorder characterised by an abnormal accumulation of triacylglycerol
      into cytoplasmic lipid droplets (LDs). NLSD-M patients are mainly affected by
      progressive myopathy, cardiomyopathy and hepatomegaly. Mutations in the PNPLA2
      gene cause variable phenotypes of NLSD-M. PNPLA2 codes for adipose triglyceride
      lipase (ATGL), an enzyme that hydrolyses fatty acids from triacylglycerol. This
      report outlines the clinical and genetic findings in a NLSD-M Italian family with
      three affected members. In our patients, we identified two novel PNPLA2 missense
      mutations (p.L56R and p.I193F). Functional data analysis demonstrated that these
      mutations caused the production of ATGL proteins able to bind to LDs, but with
      decreased lipase activity. The oldest brother, at the age of 38, had weakness and
      atrophy of the right upper arm and kyphosis. Now he is 61 years old and is unable
      to raise arms in the horizontal position. The second brother, from the age of 44,
      had exercise intolerance, cramps and pain in lower limbs. He is currently 50
      years old and has an asymmetric distal amyotrophy. One of the two sisters, 58
      years old, presents the same PNPLA2 mutations, but she is still oligo-symptomatic
      on neuromuscular examination with slight triceps muscle involvement. She suffered
      from diabetes and liver steatosis. This NLSD-M family shows a wide range of intra
      familial phenotypic variability in subjects carrying the same mutations, both in
      terms of target-organs and in terms of rate of disease progression.

PMID- 25956451
TI  - Rapid and reproducible determination of active gibberellins in citrus tissues by
      UPLC/ESI-MS/MS.
AB  - Phytohormone determination is crucial to explain the physiological mechanisms
      during growth and development. Therefore, rapid and precise methods are needed to
      achieve reproducible determination of phytohormones. Among many others,
      gibberellins (GAs) constitute a family of complex analytes as most of them share
      similar structure and chemical properties although only a few hold biological
      activity (namely GA1; GA3; GA4 and GA7). A method has been developed to extract
      GAs from plant tissues by mechanical disruption using ultrapure water as solvent
      and, in this way, ion suppression was reduced whereas sensitivity increased.
      Using this methodology, the four active GAs were separated and quantified by UPLC
      coupled to MS/MS using the isotope-labeled internal standards [(2)H2]-GA1 and
      [(2)H2]-GA4. To sum up, the new method provides a fast and reproducible protocol
      to determine bioactive GAs at low concentrations, using minimal amounts of sample
      and reducing the use of organic solvents. 

PMID- 25956452
TI  - Regulation of ascorbic acid biosynthesis and recycling during root development in
      carrot (Daucus carota L.).
AB  - Ascorbic acid (AsA), also known as vitamin C, is an essential nutrient in fruits
      and vegetables. The fleshy root of carrot (Daucus carota L.) is a good source of
      AsA for humans. However, the metabolic pathways and molecular mechanisms involved
      in the control of AsA content during root development in carrot have not been
      elucidated. To gain insights into the regulation of AsA accumulation and to
      identify the key genes involved in the AsA metabolism, we cloned and analyzed the
      expression of 21 related genes during carrot root development. The results
      indicate that AsA accumulation in the carrot root is regulated by intricate
      pathways, of which the l-galactose pathway may be the major pathway for AsA
      biosynthesis. Transcript levels of the genes encoding l-galactose-1-phosphate
      phosphatase and l-galactono-1,4-lactone dehydrogenase were strongly correlated
      with AsA levels during root development. Data from this research may be used to
      assist breeding for improved nutrition, quality, and stress tolerance in carrots.

PMID- 25956453
TI  - Disturbed temporal dynamics of brain synchronization in vision loss.
AB  - Damage along the visual pathway prevents bottom-up visual input from reaching
      further processing stages and consequently leads to loss of vision. But
      perception is not a simple bottom-up process - rather it emerges from activity of
      widespread cortical networks which coordinate visual processing in space and
      time. Here we set out to study how vision loss affects activity of brain visual
      networks and how networks' activity is related to perception. Specifically, we
      focused on studying temporal patterns of brain activity. To this end, resting
      state eyes-closed EEG was recorded from partially blind patients suffering from
      chronic retina and/or optic-nerve damage (n = 19) and healthy controls (n = 13).
      Amplitude (power) of oscillatory activity and phase locking value (PLV) were used
      as measures of local and distant synchronization, respectively. Synchronization
      time series were created for the low- (7-9 Hz) and high-alpha band (11-13 Hz) and
      analyzed with three measures of temporal patterns: (i) length of synchronized
      /desynchronized-periods, (ii) Higuchi Fractal Dimension (HFD), and (iii)
      Detrended Fluctuation Analysis (DFA). We revealed that patients exhibit less
      complex, more random and noise-like temporal dynamics of high-alpha band
      activity. More random temporal patterns were associated with worse performance in
      static (r = -.54, p = .017) and kinetic perimetry (r = .47, p = .041). We
      conclude that disturbed temporal patterns of neural synchronization in vision
      loss patients indicate disrupted communication within brain visual networks
      caused by prolonged deafferentation. We propose that because the state of brain
      networks is essential for normal perception, impaired brain synchronization in
      patients with vision loss might aggravate the functional consequences of reduced
      visual input. 

PMID- 25956454
TI  - Angiogenesis in salivary gland tumors: from clinical significance to treatment.
AB  - INTRODUCTION: Salivary gland tumors (SGTs) represent a rare cancer entity,
      consisting of various morphological features that complicate diagnosis. Their
      diversity in terms of morphology and clinical course makes defining risk factors
      difficult, while the molecular steps responsible for SGT development remain
      unclear. Angiogenesis, a hallmark of cancer development, is considered as an
      attractive target. AREAS COVERED: This review aims to summarize the available
      research regarding angiogenesis in SGTs from clinical significance to treatment
      options. EXPERT OPINION: The available data suggest that microvessel density
      (MVD) evaluation may be capable of discriminating between benign and malignant
      SGTs, while the use of CD105 antibody seems to be the most suitable. Substantial
      evidence also suggests that MVD and VEGF expression could be used as prognostic
      factors in malignant SGTs. Although several agents have shown antiangiogenic
      activities in adenoid cystic carcinoma cells and xenograft tumors, limited
      effectiveness in the existing clinical trials was noted. Further studies are
      strongly recommended for the validation of already well-known and the
      identification of novel prognostic and predictive angiogenic markers. There is
      also a strong demand for relatively larger cohorts, homogenous samples referring
      to same histological SGT subtypes and including an equivalent number of low- and
      high-grade SGTs.

PMID- 25956455
TI  - Galectin-9 as an important marker in the differential diagnosis between oral
      squamous cell carcinoma, oral leukoplakia and oral lichen planus.
AB  - OBJECTIVES: To evaluate the expression of Galectins (Gal) 1, 3 and 9,
      Metalloproteinase 3 (MMP-3) and mast cell density in oral lesions of patients
      with potentially malignant disorders (PMD) and oral squamous cell carcinomas
      (OSCC) by comparison with the controls. STUDY DESIGN: We selected 40 cases of
      PMD, 40 OSCC and 13 with normal histopathological profile. Immunohistochemistry
      was performed for Gal-1, Gal-3, Gal-9 and MMP-3. RESULTS: Gal-9 was significantly
      higher in patients with OSCC than in others groups (p < 0.001). Gal-1 expression
      was significantly lower in patients with leukoplakia than those with OSCC and
      controls (p = 0.0001). Gal-3 was significantly lower in patients with OSCC than
      those with leukoplakia (p = 0.03). MMP-3 was lower in patients with leukoplakia
      in comparison with the lichen planus group (p = 0.013). CONCLUSION: The increased
      expression of Gal-9 may be helpful to differentiate of OSCC from other oral
      cavity lesions.

PMID- 25956456
TI  - Organ inflammation in porcine Escherichia coli sepsis is markedly attenuated by
      combined inhibition of C5 and CD14.
AB  - Sepsis is an infection-induced systemic inflammatory syndrome, potentially
      causing organ failure. We previously showed attenuating effects on inflammation,
      thrombogenicity and haemodynamics by inhibiting the Toll-like receptor co-factor
      CD14 and complement factor C5 in a porcine Escherichia coli-induced sepsis model.
      The present study explored the effect on organ inflammation in these pigs. Tissue
      samples were examined from the combined treatment group (n = 8), the positive (n
      = 8) and negative (n = 6) control groups after 4h of sepsis. Inflammatory
      biomarkers were measured using ELISA, multiplex and qPCR analysis. Combined
      inhibition of C5 and CD14 markedly attenuated IL-1beta by 31-66% (P < 0.05) and
      IL-6 by 54-96% (P < 0.01) in liver, kidney, lung and spleen; IL-8 by 65-100% in
      kidney, lung, spleen, and heart (P < 0.05) and MCP-1 by 46-69% in liver, kidney,
      spleen and heart (P < 0.05). Combined inhibition significantly attenuated tissue
      factor mRNA upregulation in spleen (P < 0.05) and IP-10 mRNA upregulation in four
      out of five organs. Finally, C5aR mRNA downregulation was prevented in heart and
      kidney (P < 0.05). Combined inhibition of C5 and CD14 thus markedly attenuated
      inflammatory responses in all organs examined. The anti-inflammatory effects
      observed in lung and heart may explain the delayed haemodynamic disturbances
      observed in septic pigs receiving combined inhibition of C5 and CD14.

PMID- 25956457
TI  - The membrane attack complex as an inflammatory trigger.
AB  - The final common pathway of all routes of complement activation involves the non
      enzymatic assembly of a complex comprising newly formed C5b with the plasma
      proteins C6, C7, C8 and C9. When assembly occurs on a target cell membrane the
      forming complex inserts into and through the bilayer to create a pore, the
      membrane attack complex (MAC). On some targets, pore formation causes rapid lytic
      destruction; however, most nucleated cell targets resist lysis through a
      combination of ion pumps, membrane regulators and active recovery processes.
      Cells survive but not without consequence. The MAC pore causes ion fluxes and
      directly or indirectly impacts several important signalling pathways that in turn
      activate a diverse series of events in the cell, many of which are highly pro
      inflammatory. Although this non-lytic, pro-inflammatory role of MAC has been
      recognised for thirty years, no consensus signalling pathway has emerged. Recent
      work, summarised here, has implicated specific signalling routes and, in some
      cells, inflammasome involvement, opening the door to novel approaches to therapy
      in complement-driven pathologies.

PMID- 25956458
TI  - Capreomycin oleate microparticles for intramuscular administration: Preparation,
      in vitro release and preliminary in vivo evaluation.
AB  - Capreomycin sulfate (CS) is a second-line drug used for the treatment of
      multidrug-resistant tuberculosis (MDR-TB). The adverse effects profile and
      uncomfortable administration scheme of CS has led to the development of
      formulations based on liposomes and polymeric microparticles. However, as CS is a
      water-soluble peptide that does not encapsulate properly into hydrophobic
      particulate matrices, it was necessary to reduce its aqueous solubility by
      forming the pharmacologically active capreomycin oleate (CO) ion pair. The aim of
      this research was to develop a new formulation of CO for intramuscular injection,
      based on biodegradable microparticles that encapsulate CO in order to provide a
      controlled release of the drug with reduced local and systemic adverse effects.
      The CO-loaded microparticles prepared by spray drying or solvent emulsion
      evaporation were characterized in their morphology, encapsulation efficiency, in
      vitro/in vivo kinetics and tissue tolerance. Through scanning electron microscopy
      it was confirmed that the microparticles were monodisperse and spherical, with an
      optimal size for intramuscular administration. The interaction between CO and the
      components of the microparticle matrix was confirmed on both formulations by X
      ray powder diffraction and differential scanning calorimetry analyses. The
      encapsulation efficiencies for the spray-dried and emulsion-evaporation
      microparticles were 92% and 56%, respectively. The in vitro kinetics performed on
      both formulations demonstrated a controlled and continuous release of CO from the
      microparticles, which was successfully reproduced on an in vivo rodent model. The
      results of the histological analysis demonstrated that none of the formulations
      produced significant tissue damage on the site of injection. Therefore, the
      results suggest that injectable CO microparticles obtained by spray drying and
      solvent emulsion-evaporation could represent an interesting therapeutic
      alternative for the treatment of MDR-TB. 

PMID- 25956459
TI  - [Postoperative dehiscence of the abdominal wound and its impact on excess
      mortality, hospital stay and costs].
AB  - INTRODUCTION: The objectives of this study were to investigate the relationship
      between several factors and the incidence of postoperative abdominal wall
      dehiscence (POAD), and to estimate the influence of POAD on in-hospital
      mortality, excess length of stay and costs. METHODS: Retrospective observational
      study of a sample of abdominal surgery patients from a minimal basic data set of
      87 Spanish hospitals during 2008-2010. RESULTS: Among 323,894 admissions for
      abdominal surgery reviewed there were 2,294 patients with POAD. Elderly patients,
      male, with non-elective admission, with alcohol, tobacco or drugs abuse, and with
      more comorbidities had higher incidence. POAD patients had an increase in in
      hospital death (mortality excess of 107.5%), excess length of stay (15.6 days)
      and higher cost (14,327 euros). CONCLUSIONS: Certain demographic and behavioral
      variables, and several comorbidities are associated with the incidence of POAD,
      and this complication shows an increase in in-hospital mortality, the length of
      hospital stay and costs. Preventive measures might decrease the incidence of POAD
      and its impact on health and extra-costs.

PMID- 25956460
TI  - [Syringocystadenoma papilliferum].

PMID- 25956461
TI  - Ocular toxoplasmosis: lessons from Brazil.

PMID- 25956462
TI  - Reply: To PMID 25524494.

PMID- 25956463
TI  - Accuracy of the refractive prediction determined by multiple currently available
      intraocular lens power calculation formulas in small eyes.

PMID- 25956464
TI  - Effects of monoterpenes on ion channels of excitable cells.
AB  - Monoterpenes are a structurally diverse group of phytochemicals and a major
      constituent of plant-derived 'essential oils'. Monoterpenes such as menthol,
      carvacrol, and eugenol have been utilized for therapeutical purposes and food
      additives for centuries and have been reported to have anti-inflammatory,
      antioxidant and analgesic actions. In recent years there has been increasing
      interest in understanding the pharmacological actions of these molecules. There
      is evidence indicating that monoterpenes can modulate the functional properties
      of several types of voltage and ligand-gated ion channels, suggesting that some
      of their pharmacological actions may be mediated by modulations of ion channel
      function. In this report, we review the literature concerning the interaction of
      monoterpenes with various ion channels. 

PMID- 25956466
TI  - Cytosine modifications in myeloid malignancies.
AB  - Aberrant DNA methylation is a hallmark of many cancers, including the myeloid
      malignancies acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).
      The discovery of TET-mediated demethylation of 5-methylcytosine (5mC) and
      technological advancements in next-generation sequencing have permitted the
      examination of other cytosine modifications, namely 5-hydroxymethylcytosine
      (5hmC), in these myeloid malignancies on a genome-wide scale. Due to the
      prominence of mutations in epigenetic modifiers that can influence cytosine
      modifications in these disorders, including IDH1/2, TET2, and DNMT3A, many recent
      studies have evaluated the relative levels, distribution, and functional
      consequences of cytosine modifications in leukemic cells. Furthermore, several
      therapies are being used to treat AML and MDS that target various proteins within
      the cytosine modification pathway in an effort to revert the abnormal epigenetic
      patterns that contribute to the diseases. In this review, we provide an overview
      of cytosine modifications and selected technologies currently used to distinguish
      and analyze these epigenetic marks in the genome. Then, we discuss the role of
      mutant enzymes, including DNMT3A, TET2, IDH1/2, and the transcription factor,
      WT1, in disrupting normal patterns of 5mC and 5hmC in AML and MDS. Finally, we
      describe several therapies, both standard, front-line treatments and new drugs in
      clinical trials, aimed at inhibiting the proteins that ultimately lead to
      aberrant cytosine modifications in these diseases. 

PMID- 25956467
TI  - Therapeutic uses of somatostatin and its analogues: Current view and potential
      applications.
AB  - Somatostatin is an endogeneous cyclic tetradecapeptide hormone that exerts
      multiple biological activities via five ubiquitously distributed receptor
      subtypes. Classified as a broad inhibitory neuropeptide, somatostatin has anti
      secretory, anti-proliferative and anti-angiogenic effects. The clinical use of
      native somatostatin is limited by a very short half-life (1 to 3min) and the
      broad spectrum of biological responses. Thus stable, receptor-selective agonists
      have been developed. The majority of these somatostatin therapeutic agonists bind
      strongly to two of the five receptor subtypes, although recently an agonist of
      wider affinity has been introduced. Somatostatin agonists are established in the
      treatment of acromegaly with recently approved indications in the therapy of
      neuroendocrine tumours. Potential therapeutic uses for somatostatin analogues
      include diabetic complications like retinopathy, nephropathy and obesity, due to
      inhibition of IGF-1, VEGF together with insulin secretion and effects upon the
      renin-angiotensin-aldosterone system. Wider uses in anti-neoplastic therapy may
      also be considered and recent studies have further revealed anti-inflammatory and
      anti-nociceptive effects. This review provides a comprehensive, current view of
      the biological functions of somatostatin and potential therapeutic uses, informed
      by the wide range of pharmacological advances reported since the last published
      review in 2004 by P. Dasgupta. The pharmacology of somatostatin receptors is
      explained, the current uses of somatostatin agonists are discussed, and the
      potential future of therapeutic applications is explored. 

PMID- 25956465
TI  - Metabolic consequences of oncogenic IDH mutations.
AB  - Specific point mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2)
      occur in a variety of cancers, including acute myeloid leukemia (AML), low-grade
      gliomas, and chondrosarcomas. These mutations inactivate wild-type enzymatic
      activity and convey neomorphic function to produce d-2-hydroxyglutarate (d-2HG),
      which accumulates at millimolar levels within tumors. d-2HG can impact alpha
      ketoglutarate-dependent dioxygenase activity and subsequently affect various
      cellular functions in these cancers. Inhibitors of the neomorphic activity of
      mutant IDH1 and IDH2 are currently in Phase I/II clinical trials for both solid
      and blood tumors. As IDH1 and IDH2 represent key enzymes within the tricarboxylic
      acid (TCA) cycle, mutations have significant impact on intermediary metabolism.
      The loss of some wild-type metabolic activity is an important, potentially
      deleterious and therapeutically exploitable consequence of oncogenic IDH
      mutations and requires continued investigation in the future. Here we review how
      IDH1 and IDH2 mutations influence cellular metabolism, epigenetics, and other
      biochemical functions, discussing these changes in the context of current efforts
      to therapeutically target cancers bearing these mutations. 

PMID- 25956469
TI  - The outcome of second-look GI endoscopy in persistent gut GVHD post allogeneic
      stem cell transplantation.

PMID- 25956468
TI  - Circulating Tumor Cells in Biochemical Recurrence of Prostate Cancer.
AB  - OBJECTIVE: Circulating tumor cells (CTCs) have known prognostic implications in
      metastatic castration-resistant prostate cancer, but little is known regarding
      its utility in biochemical recurrence (BR) of prostate cancer. The primary
      objectives were to determine whether CTCs are measurable in patients with BR and
      whether it can reliably predict prostate-specific antigen (PSA) increase and PSA
      doubling times (PSADTs). METHODS: BR was identified in patients after
      prostatectomy or radiation or both, with a PSA increase of >= 0.2 for prior
      prostatectomy or > 2 mg/dL increase for post-nadir in prior radiotherapy. CTCs
      were enumerated at baseline at the time of study entry using the CellSearch
      (Janssen Diagnostics, Raritan, NJ) test. RESULTS: The median age for all 36
      patients accrued was 69.5 years (range, 51-91) with a median PSA of 1.65 ng/mL
      (range, 0.2-65.8). Gleason scores ranged from 5 to 9 (median, 7). The majority
      had prostatectomy (n = 25), external beam radiotherapy (n = 9), CyberKnife
      (Accuray, Sunnyvale, CA) (n = 1), and combined radiohormonal therapy (n = 1).
      PSADT ranged from 0.35 to 55 months, with a median of 7.43 months. The incidence
      of positive CTCs was 8.3% (3 patients), of whom 2 had biopsy-proven bony lesions
      on presenting with equivocal scans and PSADTs of 2.27 and 3.08 months,
      respectively. The third CTC-positive patient had a PSADT of 4.99 months.
      CONCLUSIONS: Obtaining CTCs in unselected patients presenting with BR has a
      relatively low yield. However, obtaining a positive CTC raises the suspicion of
      the presence of metastatic disease and may have utility for longitudinal follow
      ups of patients with BR.

PMID- 25956470
TI  - The Severity of Bowel Dysfunction in Patients with Neurogenic Bladder.
AB  - PURPOSE: Patients with neurological conditions often experience severe
      debilitating lower urinary and bowel dysfunction in addition to the physical
      disabilities. However, only the bladder has received the attention of medical
      providers with neurogenic bowel being poorly understood and characterized.
      MATERIALS AND METHODS: This is a cross-sectional analysis of a prospective
      institutional neurogenic bladder database from 2010 to 2013. RESULTS: Of the 175
      patients 60.6% had traumatic spinal cord injury and 18.3% had multiple sclerosis.
      Median +/- SD FISI (Fecal Incontinence Severity Index) scores were 18.0 +/- 1.39
      (moderate). The median neurogenic bowel dysfunction score was 11.0 +/- 0.63
      (moderate). Those scores were worse in those patients with spinal cord injury and
      spina bifida compared to those with other diseases and in younger patients (each
      p = 0.020), and those in the spinal cord injury group with higher levels of
      injury (p = 0.0046). Based on the Bristol stool scale 65% of patients had
      abnormal stool consistency, mostly constipation. None of the FISI, Bristol or
      neurogenic bowel dysfunction scores correlated significantly with SF-12(r)
      quality of life measures. However, bladder symptom scores on M-ISI (Michigan
      Incontinence Symptom Index) (p = 0.05) and AUA-SI (American Urological
      Association symptom index) (p = 0.03) correlated with FISI severity while the
      neurogenic bowel dysfunction score correlated with M-ISI (rho = 0.29, p = 0.02).
      Patients with abnormal stool consistency on the Bristol scale reported more
      urgency and stress incontinence on M-ISI. CONCLUSIONS: Bowel dysfunction is
      common among patients with neurogenic bladder. Those with worse bladder symptoms
      also experience worse bowel dysfunction. This highlights the importance of
      addressing both bowel and bladder dysfunction in this often poorly understood
      population.

PMID- 25956471
TI  - Airway-centered interstitial fibrosis: etiology, clinical findings and prognosis.
AB  - BACKGROUND: Airway-centered Interstitial Fibrosis (ACIF) is a common pathologic
      pattern observed in our practice. OBJECTIVES: The objectives of this study are to
      describe the causes associated with ACIF in a large sample of patients and its
      effect on survival. METHODS: A retrospective study in three centers of
      interstitial lung disease in Sao Paulo, between January of 1995 and December of
      2012. The surgical lung biopsy specimens were reviewed by three pathologists. The
      clinical, functional and tomographic findings were analyzed by a standardized
      protocol. RESULTS: There were 68 cases of ACIF, most of them women. The mean age
      was 57 +/- 12 yr. Dyspnea, cough, restrictive pattern at spirometry and oxygen
      desaturation at exercise were common. A reticular pattern with
      peribronchovascular infiltrates was found in 79% of the cases. The etiologies of
      ACIF were hypersensitivity pneumonitis in 29 (42.6%), gastroesophageal reflux
      disease in 17 (25.0%), collagen vascular disease in 4 (5.9%), a combination of
      them in 15 cases and idiopathic in 3 (4.4%). The median survival was 116 months
      (95% CI = 58.5 - 173.5). Lower values of oxygen saturation at rest, presence of
      cough and some histological findings--organizing tissue in the airways,
      fibroblastic foci and microscopic honeycombing--were predictors of worse
      survival. CONCLUSIONS: ACIF is an interstitial lung disease with a better
      survival when compared with IPF. The main etiologies are HP and GERD. The oxygen
      saturation at rest, the presence of cough and some histological findings are
      predictors of survival.

PMID- 25956472
TI  - Safety and feasibility of volumetric laser endomicroscopy in patients with
      Barrett's esophagus (with videos).
AB  - BACKGROUND: Volumetric laser endomicroscopy (VLE) produces high-resolution, cross
      sectional surface, and subsurface images for detecting neoplasia, targeting
      biopsies, and guiding real-time treatment. OBJECTIVE: To evaluate the safety and
      feasibility of the Nvision VLE system. DESIGN: Prospective, multicenter study.
      SETTING: Tertiary-care medical centers. PATIENTS: One hundred patients with
      suspected Barrett's esophagus, including 52 patients with prior endotherapy.
      INTERVENTIONS: The first-generation Nvision VLE Imaging System, a balloon
      centered, rotating optical probe provided images of the mucosa and submucosa
      through a 6-cm segment length and 360 degrees  scan of the distal esophagus. MAIN
      OUTCOME MEASUREMENTS: Acquisition of a complete, 6-cm scan from the distal
      esophagus, demographic and procedural data, and final histologic diagnosis.
      RESULTS: VLE imaging was successfully performed in 87 cases. After VLE imaging,
      biopsy specimens were obtained in 77 patients and mucosal resection was performed
      in 20 patients. The final pathologic diagnoses of the patients studied were
      adenocarcinoma (4 patients), high-grade dysplasia (10 patients), low-grade
      dysplasia (11 patients), indefinite (5 patients), intestinal metaplasia (29
      patients), and normal squamous cells (18 patients). VLE was not completed in 13
      of 100 (13%) because of optical probe and console issues. There were 2 minor
      adverse events (mucosal lacerations not requiring therapy). LIMITATIONS: This was
      a feasibility study with a first-generation device. There was no direct
      histopathologic correlation with the VLE images or any comparative analysis with
      white-light endoscopy or narrow-band imaging findings. CONCLUSION: VLE is a safe
      procedure for patients with suspected or confirmed Barrett's esophagus. Real-time
      VLE images enabled visualization of the mucosa and submucosa in 87% of cases.
      Further studies are needed to evaluate the in vivo diagnostic accuracy and
      clinical utility of VLE.

PMID- 25956473
TI  - Docosahexaenoic acid regulates gene expression in HUVEC cells treated with
      polycyclic aromatic hydrocarbons.
AB  - The molecular mechanism of inflammation and carcinogenesis induced by exposure of
      polycyclic aromatic hydrocarbons (PAHs) is not clearly understood. Our study was
      undertaken due to the strong pro-carcinogenic potential and reactivity of PAH
      metabolites, as well as the susceptibility of polyunsaturated fatty acids to
      oxidation. The aim of this study was to evaluate the pro- or anti-inflammatory
      impact of n-3 docosahexaenoic acid on human primary umbilical vein endothelial
      cells (HUVEC) exposed to polycyclic aromatic hydrocarbons. We analysed the
      influence of docosahexaenoic acid (DHA) and/or PAHs supplementation on the fatty
      acid profile of cell membranes, on cyclooxygenase-2 (COX-2), aryl hydrocarbon
      receptor (AHR), and glutathione S transferase Mu1 (GSTM1) protein expression as
      well as on the prostaglandin synthase 2 (PTGS2), AHR, GSTM1, PLA2G4A, and
      cytochrome P450 CYP1A1 gene expression. We observed that COX-2 and AHR protein
      expression was increased while GSTM1 expression was decreased in cells exposed to
      DHA and PAHs. Docosahexaenoic acid down-regulated CYP1A1 and up-regulated the AHR
      and PTGS2 genes. Our findings suggested that DHA contributes significantly to
      alleviate the harmful effects caused by PAHs in endothelial cells. Moreover,
      these results suggest that a diet rich in n-3 fatty acids is helpful to reduce
      the harmful effects of PAHs exposure on human living in heavily polluted areas.

PMID- 25956474
TI  - Hepato-protective effect of resveratrol against acetaminophen-induced liver
      injury is associated with inhibition of CYP-mediated bioactivation and regulation
      of SIRT1-p53 signaling pathways.
AB  - Resveratrol (RES) has been shown to possess many pharmacological activities
      including protective effect against liver damage induced by hepatotoxins. In the
      present study, the hepato-protective effect of RES against acetaminophen (APAP)
      induced liver injury in mice and the involved mechanisms was investigated. This
      study clearly demonstrated that administration of RES three days before APAP
      treatment significantly alleviated APAP-induced hepatotoxicity, as evidenced by
      morphological, histopathological, and biochemical assessments such as GSH content
      and serum ALT/AST activity. Treatment with RES resulted in significant inhibition
      of CYP2E1, CYP3A11, and CYP1A2 activities, and then caused significant inhibition
      of the bioactivation of APAP into toxic metabolite NAPQI. Pretreatment with RES
      significantly reduced APAP-induced JNK activation to protect against
      mitochondrial injury. Additionally, RES treatment significantly induced SIRT1 and
      then negatively regulated p53 signaling to induce cell proliferation-associated
      proteins including cyclin D1, CDK4, and PCNA to promote hepatocyte proliferation.
      This study demonstrated that RES prevents APAP-induced hepatotoxicity by
      inhibition of CYP-mediated APAP bioactivation and regulation of SIRT1, p53,
      cyclin D1 and PCNA to facilitate liver regeneration following APAP-induced liver
      injury.

PMID- 25956475
TI  - Human hydroxylated metabolites of BDE-47 and BDE-99 are glucuronidated and
      sulfated in vitro.
AB  - Polybrominated diphenyl ethers (PBDEs) were used worldwide as additive flame
      retardants and are classified as persistent, bioaccumulable and toxic
      environmental pollutants. In humans, the hydroxylated metabolites of 2,2',4,4'
      tetrabromodiphenyl ether (BDE-47) and 2,2',4,4',5-pentabromodiphenyl ether (BDE
      99) formed in vitro have also been detected in vivo. To further characterize the
      metabolism of BDE-47 and BDE-99 and to identify candidate markers for monitoring
      the human exposure to PBDEs using non-invasive approaches, glucuronidation and
      sulfation of hydroxylated metabolites of BDE-47 and BDE-99 were investigated
      using human liver microsomes and cytoplasm, respectively. The formed Phase II
      metabolites were analyzed by liquid chromatography-tandem mass spectrometry using
      a novel approach to develop analytical methods in absence of authentic standards.
      All available standards for hydroxylated metabolites of BDE-47 and BDE-99 were
      glucuronidated and sulfated, showing that glucuronidation and sulfation are part
      of the metabolism pathway of BDE-47 and BDE-99 in vitro. The major glucuronidated
      and sulfated analogs of hydroxylated metabolites of BDE-47 were (a) 2,4-DBP-Gluc
      and 5-Gluc-BDE-47, and (b) 2'-Sulf-BDE-28, 4-Sulf-BDE-42 and 3-Sulf-BDE-47,
      respectively. The major glucuronidated and sulfated analogs of hydroxylated
      metabolites of BDE-99 were (a) 2,4,5-TBP-Gluc and 6'-Gluc-BDE-99, and (b) 3'-Sulf
      BDE-99 and 5'-Sulf-BDE-99, respectively. Apparent Km values associated with the
      formation of sulfated metabolites of BDE-47 and BDE-99 were ten times lower than
      those of the corresponding glucuronidated metabolites, suggesting that sulfated
      rather than glucuronidated metabolites of OH-PBDEs might be used as markers of
      human exposure to PBDEs using a non-invasive approach based on urine sample
      collection.

PMID- 25956476
TI  - Expression of Lysine-specific demethylase 1 in human epithelial ovarian cancer.
AB  - BACKGROUND: Lysine-specific demethylase 1(LSD1) is implicated in the
      tumorigenesis and progression in various cancers. However, the expression of LSD1
      in epithelial ovarian cancer and its clinical significance has not been examined
      in detail. METHODS: Immunohistochemical was used to detect the expression of LSD1
      in normal ovarian epithelial tissues, cystadenoma, borderline cystadenoma, and
      cystadenocarcinoma. Next, the correlations between expression of LSD1 and
      clinicopathological features was assessed in 96 species of serous
      cystadenocarcinoma and 36 species of mucinous cystadenocarcinoma. RESULTS:
      Immunohistochemical results showed that the expression of LSD1 was gradually
      increased from benign cystadenoma and borderline cystadenoma to
      cystadenocarcinoma. The positive ratio of LSD1 expression was 50% in normal
      ovarian epithelial tissues, 72% in serous cystadenoma, 73% in mucinous
      cystadenoma, 82% in borderline serous cystadenoma, 83% in borderline mucinous
      cystadenoma, 94% in serous cystadenocarcinoma and 92% in mucinous
      cystadenocarcinoma, respectively. LSD1 expression levels were associated with
      International Federation of Gynecology and Obstetrics stage and lymphatic
      metastasis in both serous and mucinous cystadenocarcinoma samples. Kaplan-Meier
      curves suggested that overall survival time of patients with high LSD1 expression
      was significantly shorter than that of patients with low LSD1 expression.
      Multivariate Cox proportional hazard regression indicated that higher LSD1
      expression was a significant independent predictor of poor survival of EOC
      patients (P = 0.016). CONCLUSIONS: These results suggest that LSD1 may be
      involved in carcinogenesis and progression with promising therapeutic potential
      for epithelial ovarian cancer.

PMID- 25956477
TI  - Comparison of left atrial dimensions in CT and echocardiography as predictors of
      long-term success after catheter ablation of atrial fibrillation.
AB  - PURPOSE: Left atrium (LA) size is a common predictor of ablation outcomes in
      atrial fibrillation (AF), but different LA diameters have not been adequately
      studied yet. We aimed to find the best predictor of ablation outcomes using
      single-linear LA dimensions by computed tomography (CT) or echocardiography.
      METHODS: Patients (n = 103, 72 males, 59 +/- 9 years) undergoing AF ablation were
      analyzed. LA diameter (LA-D) was measured by transthoracic echocardiography
      (parasternal long axis). After 3D reconstruction of CT data (EnSite Verismo, SJM,
      MN), maximal LA dimensions were measured on a coronal plane (superior-inferior,
      SI, and transversal, TV) and a sagittal plane (anterior-posterior, AP). Volume
      (LAV) was rendered after LA appendage and pulmonary vein exclusion. RESULTS:
      Patients with persistent AF (n = 40) had significantly larger LA size than those
      with paroxysmal AF (n = 63). After 26 +/- 14 months, 31 (30 %) patients had AF
      recurrence. Univariate Cox regression analysis revealed that LA-D, LA-SI, LA-TV,
      LAV, and LAV-index (LAV/body surface area) were associated with AF recurrence.
      Multivariate Cox regression analysis revealed that LAV was the strongest
      independent predictor of AF recurrence (HR = 1.011 per ml, 95 % CI 1.003-1.020, p
      = 0.002). LA-TV had the best correlation with LAV (r = 0.69, p < 0.01) and was
      the strongest single-linear predictor (HR = 1.07 per mm, 95 % CI 1.022-1.121, p =
      0.004). Independent of LA-D, an LA-TV>74.5 mm predicted AF recurrence similarly
      to LAV>126 ml. CONCLUSIONS: LA dilatation, especially on the coronal plane, is
      associated with reduced long-term success after catheter ablation. LA-TV is the
      best linear predictor of AF recurrence, stronger than the commonly used LA-D.

PMID- 25956478
TI  - Axillary vein puncture using fluoroscopic landmarks: a safe and effective
      approach for implantable cardioverter defibrillator leads.
AB  - PURPOSE: Axillary vein puncture is an effective method for pacemaker lead
      insertion with less complications compared with subclavian vein puncture;
      however, there are limited data on implantable cardioverter defibrillator (ICD)
      implantation with this technique. We reported our experience with a blind
      axillary vein puncture using fluoroscopic landmarks consisting of the outer edge
      of the first rib and the body surface of the second rib for ICD lead
      implantation. METHODS: The study population included 103 consecutive patients
      (mean age 59 +/- 9 years) referred for ICD implantation using axillary vein
      puncture without contrast venography. An 18-gauge needle was advanced toward the
      outer edge of the fist rib below the clavicle or the body surface of the second
      rib. If the vein was not entered, the needle was withdrawn and the puncture was
      repeated with slight variations of needle direction for a maximum of four times,
      then contrast-guided vein puncture was performed. RESULTS: The total implanted
      leads were 152 including 103 right ventricular leads, 35 right atrial leads, and
      14 left ventricular epicardial leads. Blind axillary vein puncture was successful
      obtained in 96 (93.2 %) patients. The rate of success was higher using the body
      surface of the second rib compared with the outer edge of the first rib (88.7 vs.
      100 %; p = 0.04).Contrast venography was required in seven (6.8 %) patients
      because of vein course abnormality (n = 5) or vasospasm (n = 2). No acute
      complications or device-related complications were recorded during a mean follow
      up of 12 +/- 5 months. CONCLUSIONS: Axillary vein access using fluoroscopic
      landmarks, especially the body surface of the second rib, is an effective
      approach for ICD implantation and offers the potential to avoid complications
      usually observed with traditional subclavian vein approach.

PMID- 25956479
TI  - Electrolyte and hemodynamic changes following percutaneous left atrial appendage
      ligation with the LARIAT device.
AB  - PURPOSE: The left atrial appendage (LAA) is a well-known source of atrial
      natriuretic peptide (ANP) and therefore plays an important role in homeostasis.
      The neurohormonal impact of epicardial exclusion of the LAA with the LARIAT
      procedure is unknown. In this proof-of-concept study, we postulated that LAA
      exclusion would impact homeostasis as evidenced by changes in electrolytes and
      blood pressure (BP). METHODS: A total of 76 patients who underwent successful LAA
      exclusion were enrolled in this retrospective observational study utilizing a
      prospective registry. Electrolytes, BP, and heart rate (HR) were monitored before
      LARIAT and post-LARIAT (24 and 72 h and 6 months). RESULTS: There was a
      significant reduction of systolic BP (mmHg) at 24 h (113.3 +/- 16.0; p < 0.0001)
      and 72 h (119.0 +/- 18.4 mmHg; p < 0.0001) post-LARIAT when compared with pre
      LARIAT BP (138.2 +/- 21.3). The reduction in systolic BP persisted at 6-month
      follow-up (128.8 +/- 17.3; p = 0.0005). There was significant reduction in serum
      sodium (mmol/L) at 24 h (135.4 +/- 3.6; p < 0.0001) and 72 h (136.3 +/- 3.7; p <
      0.001) post-LARIAT when compared to pre-LARIAT (138.7 +/- 3.2). The reduction in
      sodium was not persistent at 6-month follow-up (138.4 +/- 3.3; p = 0.453).
      CONCLUSIONS: LAA exclusion results in an early and persistent decrease in
      systolic BP. Additionally, there is an early decline in serum sodium, which
      normalizes at long-term follow-up. The underlying mechanism leading to these
      changes is not entirely clear; however, it is likely related to neurohormonal
      changes post LAA exclusion.

PMID- 25956480
TI  - Superior efficacy of pulmonary vein isolation with online contact force
      measurement persists after the learning period: a prospective case control study.
AB  - PURPOSE: Use of online contact force (CF) measurement during circumferential
      pulmonary vein (PV) isolation (CPVI) for atrial fibrillation (AF) has
      demonstrated improvements in procedural parameters and mid-term clinical outcome.
      However, it is unknown if experience gained with CF measuring catheters improves
      the efficacy of subsequent CPVI procedures performed without CF measurement.
      METHODS: This prospective trial compared procedural results of CPVI performed
      without a CF measuring catheter to a control group performed with a CF measuring
      catheter, by an operator with prior experience with CF technology.. RESULTS:
      Thirty-six eligible paroxysmal (n = 27) or persistent (n = 9) AF patients were
      consecutively enrolled. Twelve patients underwent CPVI with the non-CF catheter
      (CF- group) in a recall period and 24 with the CF catheter (CF+ group). After the
      first circumferential lesion set, the number of PV pairs requiring additional
      touch-up lesions to achieve electrical isolation was significantly less in the
      CF+ group (2 of 48 (4.2 %) vs. 7 of 24 (29.2 %) in the CF+ and CF- groups,
      respectively, p = 0.005). The procedure time was significantly lower in the CF+
      group (117.9 +/- 23.3 vs. 134.1 +/- 25.3 min, p = 0.033). Radiofrequency (RF) and
      fluoroscopy time did not differ between groups (31.5 +/- 7.1 vs. 31.8 +/- 7.0 min
      and 11.8 +/- 5.6 vs. 11.0 +/- 5.8 min in the CF+ and the CF- group, respectively)
      CONCLUSIONS: With the use of online CF measurement, PV isolation is more
      frequently complete following the first circumferential lesion set. A previous
      learning period with direct CF feedback is not a substitute for real-time direct
      CF measurement to maintain this advantage.

PMID- 25956481
TI  - Erratum: Dumping syndrome following nissen fundoplication in an adult patient
      diagnosed by continuous online 13C/12C monitoring of (13)C-Octanoic acid breath
      test "a case report".

PMID- 25956482
TI  - Multifaceted roles of FHY3 and FAR1 in light signaling and beyond.
AB  - FAR-RED ELONGATED HYPOCOTYLS3 (FHY3) and FAR-RED-IMPAIRED RESPONSE1 (FAR1),
      initially identified as crucial components of phytochrome A (phyA)-mediated far
      red (FR) light signaling in Arabidopsis thaliana, are the founding members of the
      FAR1-related sequence (FRS) family of transcription factors present in most
      angiosperms. These proteins share extensive similarity with the Mutator-like
      transposases, indicative of their evolutionary history of 'molecular
      domestication'. Here we review emerging multifaceted roles of FHY3/FAR1 in
      diverse developmental and physiological processes, including UV-B signaling,
      circadian clock entrainment, flowering, chloroplast biogenesis, chlorophyll
      biosynthesis, programmed cell death, reactive oxygen species (ROS) homeostasis,
      abscisic acid (ABA) signaling, and branching. The domestication of FHY3/FAR1 may
      enable angiosperms to better integrate various endogenous and exogenous signals
      for coordinated regulation of growth and development, thus enhancing their
      fitness and adaptation.

PMID- 25956483
TI  - Macular morphologic findings on optical coherence tomography after microincision
      vitrectomy for proliferative diabetic retinopathy.
AB  - PURPOSE: To investigate macular morphology on spectral-domain optical coherence
      tomography (SD-OCT) images after microincision vitrectomy for vitreous hemorrhage
      associated with proliferative diabetic retinopathy (PDR). METHODS: In this
      retrospective case series, 69 eyes (57 consecutive patients) that underwent 23
      gauge microincision vitrectomy for vitreous hemorrhage due to PDR were
      investigated. Qualitative and quantitative characteristics on SD-OCT images
      [central retinal thickness, external limiting membrane (ELM), and the ellipsoid
      zone, epiretinal membranes involving the fovea, and hyperreflective foci at the
      fovea] were assessed 6 months postoperatively. Their association with the
      logarithm of the minimum angle of resolution visual acuity (logMAR VA) was
      evaluated. RESULTS: The ELM was disrupted in 15 and the ellipsoid zone in 27
      eyes, and associated significantly (P < 0.001, for both comparisons) with poor
      visual outcomes 6 months postoperatively. Hyperreflective foci in the outer
      retinal layers were associated with either a disrupted ELM or ellipsoid zone and
      poor prognoses (P < 0.001, for all comparisons). The accumulation of
      hyperreflective foci at the fovea in five eyes was correlated significantly (P <
      0.001) with poorer logMAR VA. Twenty-nine eyes had center-involved diabetic
      macular edema 6 months postoperatively, whereas the central thickness was not
      correlated with the logMAR VA (R = -0.148, P = 0.224). Eight eyes with either
      epiretinal membrane on SD-OCT images had greater central thickness (P = 0.003),
      although there were no differences in the logMAR VA between eyes with and without
      it (P = 0.648). CONCLUSIONS: Foveal photoreceptor damage is associated with poor
      visual outcomes after microincision vitrectomy for vitreous hemorrhage due to
      PDR.

PMID- 25956484
TI  - A Co-blended Locust Bean Gum and Polymethacrylate-NaCMC Matrix to Achieve Zero
      Order Release via Hydro-Erosive Modulation.
AB  - Locust bean gum (LBG) was blended with a cellulose/methacrylate-based
      interpolyelectrolyte complex (IPEC) to assess the hydro-erosive influence of
      addition of a polysaccharide on the disposition and drug delivery properties
      inherent to IPEC matrix. The addition of LBG modulated the drug (levodopa)
      release characteristics of the IPEC by reducing excessive swelling and preventing
      bulk erosion. After 8 h in pH 4.5 dissolution medium, gravimetric analysis
      established that IPEC tablet matrix eroded by 30% of the initial weight due to
      bulk erosion while LBG-blended IPEC (LBG-b-IPEC) demonstrated surface erosion
      accounting to 62% of initial weight (596->226.8 mg). Mathematical modeling of the
      drug release data depicted a transformation from non-Fickian mechanism (IPEC
      matrices) to zero-order drug release pattern (LBG-b-IPEC matrices) with the
      linearity of release profile being close to 1 (R (2) = 0.99). Physicochemical
      characterizations employing Fourier transform infrared spectroscopy (FTIR) and
      differential scanning calorimetry (DSC) explicated that LBG interacted with IPEC
      by its hydrophilic groups associating with the existing water-holding bodies of
      IPEC to produce compact matrices. The lattice atomistic modeling elucidated that
      LBG acted as a linker with the formation of intra- and intermolecular hydrogen
      bonds generating a highly stabilized polysaccharide-polyelectrolytic structure
      which influenced the improved properties observed.

PMID- 25956485
TI  - Comparison of Univariate and Multivariate Models of 13C SSNMR and XRPD Techniques
      for Quantification of Nimodipine Polymorphs.
AB  - The focus of the present investigation was to explore the use of solid-state
      nuclear magnetic resonance ((13)C ssNMR) and X-ray powder diffraction (XRPD) for
      quantification of nimodipine polymorphs (form I and form II) crystallized in a
      cosolvent formulation. The cosolvent formulation composed of polyethylene glycol
      400, glycerin, water, and 2.5% drug, and was stored at 5 degrees C for the drug
      crystallization. The (13)C ssNMR and XRPD data of the sample matrices containing
      varying percentages of nimodipine form I and form II were collected. Univariate
      and multivariate models were developed using the data. Least square method was
      used for the univariate model generation. Partial least square and principle
      component regressions were used for the multivariate models development. The
      univariate models of the (13)C ssNMR were better than the XRPD as indicated by
      statistical parameters such as correlation coefficient, R (2), root mean square
      error, and standard error. On the other hand, the XRPD multivariate models were
      better than the (13)C ssNMR as indicated by precision and accuracy parameters.
      Similar values were predicted by the univariate and multivariate models for
      independent samples. In conclusion, the univariate and multivariate models of
      (13)C ssNMR and XRPD can be used to quantitate nimodipine polymorphs.

PMID- 25956486
TI  - Topical Delivery of 5-Fluorouracil from PheroidTM Formulations and the In Vitro
      Efficacy Against Human Melanoma.
AB  - Drug delivery vehicles can influence the topical delivery and the efficacy of an
      active pharmaceutical ingredient (API). In this study, the influence of PheroidTM
      technology, which is a unique colloidal drug delivery system, on the skin
      permeation and antimelanoma efficacy of 5-fluorouracil were investigated. Lotions
      containing PheroidTM with different concentrations of 5-fluorouracil were
      formulated then used in Franz cell skin diffusion studies and tape stripping. The
      in vitro efficacy of 5-fluorouracil against human melanoma cells (A375) was
      investigated using a flow cytometric apoptosis assay. Statistically significant
      concentrations of 5-fluorouracil diffused into and through the skin with
      PheroidTM formulations resulting in an enhanced in vitro skin permeation from the
      4.0% 5-fluorouracil lotion (p < 0.05). The stratum corneum-epidermis and
      epidermis-dermis retained 5-fluorouracil concentrations of 2.31 and 6.69 MUg/ml,
      respectively, after a diffusion study with the 4.0% PheroidTM lotion. Subsequent
      to the apoptosis assay, significant differences were observed between the effect
      of 13.33 MUg/ml 5-fluorouracil in PheroidTM lotion and the effects of the
      controls. The results obtained suggest that the PheroidTM drug delivery system
      possibly enhances the flux and delivery of 5-fluorouracil into the skin.
      Therefore, using PheroidTM could possibly be advantageous with respect to topical
      delivery of 5-fluorouracil.

PMID- 25956487
TI  - Probiotics can improve the clinical outcomes of hepatic encephalopathy: An update
      meta-analysis.
AB  - INTRODUCTION: Although the efficacy of probiotics has been extensively studied in
      hepatic encephalopathy (HE), the results remain controversial. The objective of
      this study is to identify and update the association between probiotics and HE.
      METHODS: Up to December 2014, we searched Medline, Embase, Web of Science,
      Cochrane CENTRAL, and SinoMed of China for all relevant articles about probiotics
      and HE. Jadad score was used to evaluate the quality of studies. Pooled relative
      risk (RR), publication bias and heterogeneity were assessed. RESULTS: Nine
      studies met the inclusion criteria. Probiotics was associated with improvement of
      minimal HE and prophylaxis of overt HE [RR 1.52; 95% confidence intervals (95%
      CI) 1.00-2.33]. Studies with probiotics showed reduction of ammonia concentration
      [standard mean difference (SMD) -0.32, 95% CI -0.54 to -0.11]. Probiotics could
      reduce physical and psychosocial sickness impact profile (SIP) score with weight
      mean difference (WMD) -3.13 (95% CI -4.10 to -2.17) and WMD -3.50 (95% CI -4.91
      to -2.08), respectively. Similar result was obtained with total SIP score (WMD 
      4.83; 95% CI -6.24 to -3.43). Reduction of severe adverse events, defined as
      minimal HE developing into overt HE, hospitalizations, infections or unrelated
      emergency room (ER) visits, was observed in HE with probiotics (RR 0.59; 95% CI
      0.39-0.90). CONCLUSION: Our pooled results indicated that probiotics was
      associated with improvement of minimal HE, prophylaxis of overt HE, and reduction
      of SIP score and severe adverse events. Large well-designed randomised controlled
      trials are needed to confirm these results.

PMID- 25956488
TI  - Sorafenib-induced hand-foot syndrome.

PMID- 25956489
TI  - Helicobacter pylori in celiac disease and in duodenal intraepithelial
      lymphocytosis: Active protagonist or innocent bystander?
AB  - BACKGROUND AND OBJECTIVE: Helicobacter pylori (H. pylori) infection influences
      duodenal inflammation. Consequently, in celiac disease and in duodenal
      intraepithelial lymphocytosis, the bacterium could affect the clinical
      histological manifestations. The aim of this work was to evaluate the prevalence
      and the potential role of H. pylori infection in celiac disease and duodenal
      intraepithelial lymphocytosis. METHODS: H. pylori status was reviewed in 154
      patients with celiac disease or duodenal intraepithelial lymphocytosis and in a
      control population. This retrospective study was performed at Molinette hospital,
      university of Torino, Italy. RESULTS: H. pylori prevalence was 36% in celiac
      disease patients, 19% in case of duodenal intraepithelial lymphocytosis and 41%
      in controls (P<0.05 vs. duodenal intraepithelial lymphocytosis). H. pylori
      prevalence was not significantly different between celiac disease patients with
      or without iron deficiency anemia (22% vs. 39%) and it was higher in patients
      with milder duodenal lesions: 50% in Marsh-Oberhuber classification type 1-2 vs.
      33% in type 3. Celiac disease patients had a mean intraepithelial lymphocytes
      count greater than that of duodenal intraepithelial lymphocytosis patients (52
      vs. 44 intraepithelial lymphocytes per 100 epithelial cells). Both in celiac
      disease and in duodenal intraepithelial lymphocytosis patients, H. pylori
      infection was associated with an increase in intraepithelial lymphocytes count,
      but this difference was not significant. CONCLUSION: H. pylori prevalence was
      similar in celiac disease patients and in controls and higher in patients with
      milder duodenal lesions. There was no association between H. pylori infection and
      duodenal intraepithelial lymphocytosis.

PMID- 25956490
TI  - Association between portal vein thrombosis and risk of bleeding in liver
      cirrhosis: A systematic review of the literature.
AB  - AIMS: A systematic review of the literature was conducted to explore the
      association of portal vein thrombosis (PVT) with the risk of bleeding in liver
      cirrhosis. METHODS: PubMed, EMBASE, and Cochrane library databases were searched
      for all relevant papers, which compared the prevalence of bleeding at baseline
      and/or incidence of bleeding during follow-up between cirrhotic patients with and
      without PVT. RESULTS: Eighteen papers were eligible for this systematic review.
      The heterogeneity among studies was marked with regards to the treatment
      modalities, sources of bleeding, lengths of follow-up, and ways of data
      expression. But most of their findings were homozygous and suggested that the
      cirrhotic patients with PVT were more likely to have previous histories of
      bleeding at their admission and to develop de novo bleeding and/or rebleeding
      during the short- and long-term follow-up. The association of PVT with the risk
      of bleeding might be weakened in the multivariate analyses. Additionally, as for
      the cirrhotic patients with gastric variceal bleeding treated with
      medical/endoscopic therapy, the association of PVT with the risk of rebleeding
      remained controversial in 2 studies; as for the cirrhotic patients undergoing
      transjugular intrahepatic portosystemic shunts for the management of variceal
      bleeding, a pre-existing PVT was not associated with the risk of rebleeding.
      CONCLUSIONS: Based on a systematic review of the literature, there was a positive
      association between the presence of PVT and risk of bleeding in liver cirrhosis
      in most of clinical conditions. However, whether PVT aggravated the development
      of bleeding during follow-up needed to be further explored.

PMID- 25956491
TI  - Investigation of acetaminophen toxicity in HepG2/C3a microscale cultures using a
      system biology model of glutathione depletion.
AB  - We have integrated in vitro and in silico information to investigate
      acetaminophen (APAP) and its metabolite N-acetyl-p-benzoquinone imine (NAPQI)
      toxicity in liver biochip. In previous works, we observed higher cytotoxicity of
      HepG2/C3a cultivated in biochips when exposed to 1 mM of APAP for 72 h as
      compared to Petri cultures. We complete our investigation with the present in
      silico approach to extend the mechanistic interpretation of the intracellular
      kinetics of the toxicity process. For that purpose, we propose a mathematical
      model based on the coupling of a drug pharmacokinetic model (PK) with a systemic
      biology model (SB) describing the reactive oxygen species (ROS) production by
      NAPQI and the subsequent glutathione (GSH) depletion. The SB model was
      parameterized using (i) transcriptomic data, (ii) qualitative results of time
      lapses ROS fluorescent curves for both control and 1-mM APAP-treated experiments,
      and (iii) additional GSH literature data. The PK model was parameterized (i)
      using the in vitro kinetic data (at 160 MUM, 1 mM, 10 mM), (ii) using the
      parameters resulting from a physiologically based pharmacokinetic (PBPK)
      literature model for APAP, and (iii) by literature data describing NAPQI
      formation. The PK-SB model predicted a ROS increase and GSH depletion due to the
      NAPQI formation. The transition from a detoxification phase and NAPQI and ROS
      accumulation was predicted for a NAPQI concentration ranging between 0.025 and
      0.25 MUM in the cytosol. In parallel, we performed a dose response analysis in
      biochips that shows a reduction of the final hepatic cell number appeared in
      agreement with the time and doses associated with the switch of the NAPQI
      detoxification/accumulation. As a result, we were able to correlate in vitro
      extracellular APAP exposures with an intracellular in silico ROS accumulation
      using an integration of a coupled mathematical and experimental liver on chip
      approach.

PMID- 25956492
TI  - Reliability and reproducibility of quantitative assessment of left ventricular
      function and volumes with 3-slice segmentation of cine steady-state free
      precession short axis images.
AB  - OBJECTIVES: Quantitative assessment of left ventricular (LV) functional
      parameters in cardiac MR requires time-consuming contour tracing across multiple
      short axis images. This study assesses global LV functional parameters using 3
      slice segmentation on steady state free precision (SSFP) cine short axis images
      and compares the results with conventional multi-slice segmentation of LV.
      METHODS: Data were collected from 61 patients who underwent cardiac MRI for
      various clinical indications. Semi-automated cardiac MR software was used to
      trace LV contours both at multiple slices from base to apex as well as just 3
      slices (base, mid, and apical) by two readers. Left ventricular ejection fraction
      (LVEF), LV volumes, and LV mass were calculated using both methods. RESULTS:
      Bland-Altman plot revealed narrow limits of agreement (-4.4% to 5.1%) between
      LVEF obtained by the two methods. Bland-Altman analysis showed slightly wider
      limits of agreement between end-diastolic volumes (-5.0 to 12.0%; -3.9 to 8.5
      ml/m(2)), end-systolic volumes (-10.9 to 14.7%; -4.1 to 6.5 ml/m(2)), and LV mass
      (-5.2 to 12.7%; -4.8 to 10.2g/m(2)) obtained by the two methods. There was a
      small mean difference between LV volumes and LV mass obtained using multi-slice
      and 3-slice segmentation. No statistically significant difference existed between
      the LV parameters obtained by the two readers using 3-slice segmentation
      (p>0.05). Multi-slice assessment required approximately 15 min per study while 3
      slice assessment required less than 5 min. CONCLUSIONS: 3-slice segmentation of
      the left ventricle at basal, mid, and apical levels on cine SSFP short axis
      images can provide rapid and reliable assessment of LVEF with good
      reproducibility. The 3-slice method also provides a reasonable estimate of the LV
      volumes and LV mass.

PMID- 25956493
TI  - Value of CT angiography in anterior circulation large vessel occlusive stroke:
      Imaging findings, pearls, and pitfalls.
AB  - Hyperacute stroke imaging is playing an increasingly important role in
      determining management decisions in acute stroke patients, particularly patients
      with large vessel occlusive stroke who may benefit from endovascular
      intervention. CT angiography (CTA) is an important tool in the work-up of the
      acute stroke patient. It reliably detects large occlusive thrombi in proximal
      cerebral arteries and is a quick and highly accurate method in identifying
      candidates for endovascular stroke treatment. In this article we review the
      imaging findings on CTA in acute large vessel occlusive stroke using a pictorial
      case based approach. We retrospectively reviewed CTA studies in 48 patients
      presenting with acute anterior circulation large vessel occlusive stroke who were
      brought for intra-arterial acute stroke intervention. We discuss and illustrate
      patterns of proximal intracranial arterial occlusion, collateralization to the
      occluded territory, as well as reviewing some important pearls, pitfalls and
      teaching points in CTA assessment of the acute stroke patient. Performed from the
      level of the aortic arch CTA also gives valuable information regarding the state
      of other vessels in the acute stroke patient, identifying additional significant
      vascular stenoses or occlusions, and as we illustrate, can demonstrate other
      clinically significant findings which may impact on patient management and
      outcome. 

PMID- 25956494
TI  - Comparison of T1rho imaging between spoiled gradient echo (SPGR) and balanced
      steady state free precession (b-FFE) sequence of knee cartilage at 3T MRI.
AB  - PURPOSE: To investigate the difference in T1rho profiles of the entire femoral
      cartilage between SPGR and b-FFE sequences at 3.0T. MATERIALS AND METHODS: 20
      healthy volunteers were enrolled in this study. T1rho images of each subject were
      acquired with two types of pulse sequences: SPGR and b-FFE. Femoral cartilage
      segmentation was performed by two independent raters slice-by-slice using Matlab.
      Inter- and intra-observer reproducibility between the two imaging protocols was
      calculated. The relative signal intensity (SI) of cartilage, subchondral bone
      marrow, joint effusion, and the relative signal contrast between structures of
      the knee were quantitatively measured. The difference in T1rho values between
      SPGR and b-FFE sequences was statistically analyzed using the Wilcoxon signed
      rank test. RESULTS: The average T1rho value of the entire femoral cartilage with
      b-FFE was significantly higher compared to SPGR (p<0.05). The reproducibility of
      the segmented area and T1rho values was superior with SPGR compared to b-FFE. The
      inter-class correlation coefficient was 0.846 on SPGR and 0.824 on b-FFE. The
      intra-class correlation coefficient of T1rho values was 0.878 on SPGR and 0.836
      on b-FFE. The two imaging techniques demonstrated different signal and contrast
      characteristics. The relative SI of fluid was significantly higher on SPGR, while
      the relative SI of subchondral bone was significantly higher on b-FFE (p<0.001).
      There were also significant differences in the relative contrast between fluid
      cartilage, fluid-subchondral bone, and cartilage-subchondral bone between the two
      sequences (all p<0.001). CONCLUSION: We need to pay attention to differences in
      T1rho values between SPGR and b-FFE in clinical applications.

PMID- 25956495
TI  - Polyradiculopathy secondary to severe hypertriglyceridemia.
AB  - A 74-year-old man presented with a subacute severe thoracic polyradiculopathy
      affecting the T4-T8 dermatomes bilaterally. Extensive investigation demonstrated
      markedly raised triglyceride levels of 44 mmol/L (<1.7). The patient's unique
      presentation is discussed alongside a review of triglyceride-induced
      neurotoxicity and therapeutic management. 

PMID- 25956496
TI  - Rheumatoid lung.

PMID- 25956497
TI  - Detection of alkaptonuria in a 1-week-old infant.
AB  - Alkaptonuria is a rare disorder that results from an inherited deficiency of
      aromatic amino acid metabolism. Only 21% of the children under the age of 1 year
      having the disease are identified in clinics. We report a case of a 1-week-old
      child of a first-degree consanguineous couple with a symptom of frequent nappy
      staining. Analysis of urine showed a homogentisic acid concentration exceeding
      200 mg/dL. The physical examination revealed that the child was healthy. The
      parents' watchfulness and the close attention paid to the child were the keys to
      the early detection of this rare disease. After identifying the disease, adequate
      follow-up of the patient is important to reduce further complications. Anti
      inflammatory therapy and increasing the muscle strength by exercises such as
      swimming would be useful to restrict joint pains and immobilisation. A low
      protein diet also could be recommended; that fact is yet to be proven by clinical
      trials. 

PMID- 25956498
TI  - Biotinidase deficiency mimicking primary immune deficiencies.
AB  - Biotinidase deficiency (BD) is an inborn metabolic disorder inherited in an
      autosomal recessive manner. Partially due to high consanguinity rates in Turkey,
      BD incidence is high in Turkey. If left untreated, neurological abnormalities
      including seizures, hypotonia, sensorineural deafness, alopecia, egzamatous skin
      rash and candidiasis may occur. Three-years-old girl was admitted to hospital
      with recurrent infections, candidiasis and egzamatous skin rash. Immunological
      evaluation was normal. Associated deafness and consanguinity of the parents
      suggested BD which has been proven by enzyme activity measurement. With this
      report, we want to emphasise that BD can be the underlying cause of recurrent
      infections and candidiasis. 

PMID- 25956499
TI  - Involving Medical Students in Informed Consent: A Pilot Study.
AB  - INTRODUCTION: Studies have reported that patients often sign consent documents
      without understanding the content. Written paperwork, audio-visual materials, and
      decision aids have shown to consistently improve patients' knowledge. How
      informed consent should be taken is not properly taught at most universities in
      Germany. MATERIALS AND METHODS: In this cross-sectional study, we investigated
      how much information about their procedure our patients retain. In particular, it
      should be elucidated whether an additional conversation between patients and
      properly prepared medical students shortly before surgery as an adjunct to
      informed consent can be introduced as a new teaching unit aimed to increase the
      understanding of surgery by patients and students. Informed consent of all
      patients had been previously obtained by three surgical residents 1-3 days in
      advance. All patients had received a copy of their consent form. The same
      residents developed assessment forms for thyroidectomy, laparoscopic
      cholecystectomy, umbilical hernia repair, and Lichtenstein procedure for inguinal
      hernia, respectively, containing 3-4 major common complications (e.g., bile duct
      injury, hepatic artery injury, stone spillage, and retained stones for
      laparoscopic cholecystectomy) and briefed the medical students before seeing the
      patients. Structured one-to-one interviews between students (n = 9) and patients
      (n = 55) based on four different assessment forms were performed and recorded by
      students. Both patients and students were asked to assess the new teaching unit
      using a short structured questionnaire. RESULTS: Although 100% of patients said
      at the beginning of their interview to have understood and memorized the risks of
      their imminent procedure, 5.8% (3/55) were not even able to indicate the correct
      part of the body where the incision would take place. Only 18.2% (10/55) of the
      patients were able to mention 2 or more complications, and 45.3% (25/55) could
      not even recall a single one. 96.4% (53/55) of the patients and 100% (9/9) of the
      students taking part in this teaching unit found that this exercise represents a
      significant improvement of clinical teaching and recommended to introduce this
      teaching unit as a standard on the normal wards. CONCLUSION AND OUTLOOK: Students
      teaching patients (SteP) appears to be an easy and cost-efficient tool to improve
      patients' education and students' learning. Students become aware of how
      difficult it is to explain surgical procedures and complications to patients and
      patients are better informed about their treatment. We plan to (i) introduce the
      STeP protocol as a standard teaching project in daily clinical routine and (ii)
      continue the pilot study to reach representative student and patient numbers for
      a possible final statement and derived recommendation.

PMID- 25956500
TI  - Localization of sesquiterpene lactone biosynthesis in cells of capitate glandular
      trichomes of Helianthus annuus (Asteraceae).
AB  - Capitate glandular trichomes (CGT) of sunflower, Helianthus annuus, synthesize
      bioactive sesquiterpene lactones (STLs) within a short period of only a few days
      during trichome development. In the current project, the subcellular localization
      of H. annuus germacrene A monooxygenase (HaGAO), a key enzyme of the STL
      biosynthesis in sunflower CGT, was investigated. A polyclonal antibody raised
      against this enzyme was used for immunolabelling. HaGAO was found in secretory
      and stalk cells of CGT. This correlated with the appearance of smooth endoplasmic
      reticulum in both cell types. Stalk cells and secretory cells differed in form,
      size and types of plastids, but both had structures necessary for secretion. No
      HaGAO-specific immunoreaction was found in sunflower leaf tissue outside of CGT
      or in developing CGT before the secretory phase had started. Our results
      indicated that not only secretory cells but also nearly all cells of the CGT were
      involved in the biosynthesis of STL and that this process was not linked to the
      presence or absence of a specific type of plastid.

PMID- 25956501
TI  - Autophagy in the fat body cells of the cave cricket Troglophilus neglectus
      Krauss, 1878 (Rhaphidophoridae, Saltatoria) during overwintering.
AB  - The cave cricket Troglophilus neglectus regularly overwinters for 4-5 months in
      hypogean habitats. Winter dormancy is a natural starvation period, providing the
      opportunity to study autophagy under natural conditions. We aimed to evaluate the
      autophagic activity in adipocytes and urocytes of the fat body in three time
      frames: directly before overwintering, in the middle of dormancy, and at its end.
      For this purpose, we sampled individuals in caves. The cell ultrastructure was
      studied by transmission electron microscopy (TEM) and the abundance of
      autophagosomes by immunofluorescence microscopy (IFM), applying the widely used,
      specific immunolabeling marker microtubule-associated protein 1 light chain 3
      (LC3). Before overwintering, TEM revealed scarce autophagosomes and residual
      bodies in the adipocytes and none in the urocytes. Congruently, IFM showed a very
      limited or no reaction. In the middle and at the end of overwintering, in both
      cell types, phagophores, autophagosomes, autolysosomes, and residual bodies were
      identified by TEM, while LC3 immunolabeling for detecting autophagosomes showed a
      conspicuous positive reaction. Both methods revealed that there were no
      significant differences between the sexes in any time frame. Minimal autophagic
      activity was detected before the winter dormancy, and it gradually intensified
      till the end of overwintering, probably because reserve proteins in protein
      granula are not composed of all the required amino acids. We conclude that in T.
      neglectus, autophagy is a substantial response to starvation and supports
      homeostatic processes during winter dormancy by supplying cells with nutrients.

PMID- 25956502
TI  - Evolutionary conservation of TORC1 components, TOR, Raptor, and LST8, between
      rice and yeast.
AB  - Target of rapamycin (TOR) is a conserved eukaryotic serine/threonine kinase that
      functions as a central controller of cell growth. TOR protein is structurally
      defined by the presence several conserved domains such as the HEAT repeat, focal
      adhesion target (FAT), FKBP12/rapamycin binding (FRB), kinase, and FATC domains
      starting from the N-terminus. In most eukaryotes, TOR forms two distinct physical
      and functional complexes, which are termed as TOR complex 1 (TORC1) and TORC2.
      However, plants contain only TORC1 components, i.e., TOR, Raptor, and LST8. In
      this study, we analyzed the gene structure and functions of TORC components in
      rice to understand the properties of the TOR complex in plants. Comparison of the
      locations of introns in these genes among rice and other eukaryotes showed that
      they were well conserved among plants except for Chlamydomonas. Moreover, the
      intron positions in the coding sequence of human Raptor and LST8 were closer to
      those of plants than of fly or nematode. Complementation tests of rice TOR
      (OsTOR) components in yeast showed that although OsTOR did not complement yeast
      tor mutants, chimeric TOR, which consisted of the HEAT repeat and FAT domain from
      yeast and other regions from rice, rescued the tor mutants, indicating that the
      HEAT repeat and FAT domains are important for species-specific signaling.
      OsRaptor perfectly complemented a kog1 (yeast Raptor homolog) mutant, and OsLST8
      partially complemented an lst8 mutant. Together, these data suggest the
      importance of the N-terminal region of the TOR, HEAT, and FAT domains for
      functional diversification of the TOR complex. 

PMID- 25956504
TI  - The Pharmacokinetics and Tissue Distribution of Honokiol and its Metabolites in
      Rats.
AB  - Honokiol (HK) is the main bioactive compound isolated from the bark of Magnolia
      officinalis. The present work is the first to report the pharmacokinetics and
      distribution of HK and its two metabolites of hydroxylated HK conjugated with
      glucuronic and sulfuric acid (M1) and HK monoglucuronide (M2) in plasma, liver,
      kidney and brain following oral administration of HK (40 mg/kg) to healthy Wistar
      rats. The results showed that only HK but not M1 or M2 was found in brain.
      Additionally, our work indicated that M2 not HK was the major compound in liver
      and plasma. The elimination of HK in liver, kidney and brain, and M2 in liver and
      kidney was more rapid than in plasma. The finding suggested that some of the
      pharmacological activity of HK might be generated by M2 but not HK. 

PMID- 25956503
TI  - Activation of Notch1 signalling promotes multi-lineage differentiation of c
      Kit(POS)/NKX2.5(POS) bone marrow stem cells: implication in stem cell
      translational medicine.
AB  - INTRODUCTION: Transplantation of bone marrow mesenchymal stem cells (BMSCs) can
      repair injured hearts. However, whether BMSC populations contain cells with
      cardiac stem cell characteristics is ill-defined. We report here that Notch
      signalling can promote differentiation of c-Kit(POS)/NKX2.5(POS) BMSCs into
      cardiomyocyte-like cells. METHODS: Total BMSCs were isolated from Sprague-Dawley
      rat femurs and c-Kit(POS) cells were purified. c-Kit(POS)/NKX2.5(POS) cells were
      isolated by single-cell cloning, and the presence of cardiomyocyte, smooth muscle
      cell (SMC), and endothelial cell differentiation markers assessed by
      immunofluorescence staining and semi-quantitative reverse-transcription
      polymerase chain reaction (RT-PCR) analysis. Levels of c-Kit and Notch1-4 in
      total BMSCs and c-Kit(POS)/NKX2.5(POS) BMSCs were quantitated by flow cytometry.
      Following infection with an adenovirus over-expressing Notch1 intracellular
      domain (NICD), total BMSCs and c-Kit(POS)/NKX2.5(POS) cells were assessed for
      differentiation to cardiomyocyte, SMC, and endothelial cell lineages by
      immunofluorescence staining and real-time quantitative RT-PCR. Total BMSCs and c
      Kit(POS)/NKX2.5(POS) cells were treated with the Notch1 ligand Jagged1 and
      markers of cardiomyocyte, SMC, and endothelial cell differentiation were examined
      by immunofluorescence staining and real-time quantitative RT-PCR analysis.
      RESULTS: c-Kit(POS)/NKX2.5(POS) cells were present among total BMSC populations,
      and these cells did not express markers of adult cardiomyocyte, SMC, or
      endothelial cell lineages. c-Kit(POS)/NKX2.5(POS) BMSCs exhibited a multi-lineage
      differentiation potential similar to total BMSCs. Following sorting, the c-Kit
      level in c-Kit(POS)/NKX2.5(POS) BMSCs was 84.4%. Flow cytometry revealed that
      Notch1 was the predominant Notch receptor present in total BMSCs and c
      Kit(POS)/NKX2.5(POS) BMSCs. Total BMSCs and c-Kit(POS)/NKX2.5(POS) BMSCs
      overexpressing NICD had active Notch1 signalling accompanied by differentiation
      into cardiomyocyte, SMC, and endothelial cell lineages. Treatment of total BMSCs
      and c-Kit(POS)/NKX2.5(POS) BMSCs with exogenous Jagged1 activated Notch1
      signalling and drove multi-lineage differentiation, with a tendency towards
      cardiac lineage differentiation in c-Kit(POS)/NKX2.5(POS) BMSCs. CONCLUSIONS: c
      Kit(POS)/NKX2.5(POS) cells exist in total BMSC pools. Activation of Notch1
      signalling contributed to multi-lineage differentiation of c-Kit(POS)/NKX2.5(POS)
      BMSCs, favouring differentiation into cardiomyocytes. These findings suggest that
      modulation of Notch1 signalling may have potential utility in stem cell
      translational medicine.

PMID- 25956505
TI  - Re: Re: Cross-sectional audit on the relevance of Elevated National Early Warning
      Score in medical patients at a Model 2 hospital in Ireland.

PMID- 25956506
TI  - Induction of anterior gradient 2 (AGR2) plays a key role in insulin-like growth
      factor-1 (IGF-1)-induced breast cancer cell proliferation and migration.
AB  - Anterior gradient 2 (AGR2) is a promising anti-tumor target associated with
      estrogen receptor expression and metastatic progression of breast cancer. Insulin
      like growth factor-1 (IGF-1) is another potent factor that stimulates breast
      cancer progression and mediates anti-estrogen drug resistance. However, the
      precise mechanism and connections between these two factors in breast cancer drug
      resistance have not been fully elucidated. Here, for the first time, we decipher
      that IGF-1 remarkably induces AGR2 in the MCF7 cell line, through an estrogen
      response element (ERE) between -802 and -808 bp and a leucine zipper
      transcription factor-binding site located between -972 and -982 bp on the AGR2
      promoter. We also found that the ERK1/2 and AKT pathways mediate estrogen
      receptor-alpha at the upstream of ERE and that the JNK pathway activates the
      leucine zipper site through the c-Jun/c-Fos complex. Additionally, our data
      suggest that knockdown of AGR2 reduces IGF-1-induced cell proliferation,
      migration and cell cycle progression. Therefore, we report that AGR2 is a key
      modulator involved in IGF-1-induced breast cancer development. We propose that
      the identification of the mechanism linking the IGF-1/insulin signal and AGR2
      promoter activation is important, because it provides insights into the
      development of anti-breast cancer drugs.

PMID- 25956507
TI  - Obstetric and psychological characteristics of women seeking multiple abortions
      in the region of Monastir (Tunisia): results of a cross-sectional design.
AB  - BACKGROUND: Repeat abortion is a public health concern favored by many obstetric
      and social factors. The purpose of our study was to identify associated factors
      to repeated abortion in the region of Monastir (Tunisia). Common mental disorders
      (CMD) such as anxiety and depression were also evaluated in women seeking
      voluntary repeated abortion. METHODS: We carried out a cross sectional study
      between January and April 2013 in the Reproductive Health Center (RHC) of the
      region of Monastir in Tunisia (This study is part of a prospective design on
      mental disorders and intimate partner violence among women seeking abortions in
      the RHC). Among women referred to the RHC we selected those seeking voluntary
      abortion (medical or surgical method). Data on women's demographic characters,
      knowledge and practices about contraceptive methods and abortion were collected
      the abortion day via a structured questionnaire. Data about anxiety and
      depression status were evaluated during the post-abortal control visit at 3-4
      weeks following pregnancy termination. RESULTS: Of the 500 interviewed women, 211
      (42.2 %; CI95% [37.88 - 46.52]) were seeking repeated abortions. Multivariate
      analysis showed that increased age, lower level of women school education, single
      status, poor knowledge about birth control methods and history of conflict/abuse
      by a male partner, were uniquely associated with undergoing repeat compared with
      initial abortion. CMD were significantly higher in women undergoing second or
      subsequent abortion (51.1 %) single and lower educated women. Women relating a
      history of conflicts/abuse report more CMD than others (30.6 % vs 20.8 %).
      CONCLUSION: Health facilities providing abortion services need to pay more
      attention to women seeking repeat abortion. Further studies are needed to well
      establish the relation between the number of abortion and the occurrence and the
      severity of CMD.

PMID- 25956508
TI  - Variation of the group 5 grass pollen allergen content of airborne pollen in
      relation to geographic location and time in season.
AB  - BACKGROUND: Allergies to grass pollen are the number one cause of outdoor hay
      fever. The human immune system reacts with symptoms to allergen from pollen.
      OBJECTIVE: We investigated the natural variability in release of the major group
      5 allergen from grass pollen across Europe. METHODS: Airborne pollen and
      allergens were simultaneously collected daily with a volumetric spore trap and a
      high-volume cascade impactor at 10 sites across Europe for 3 consecutive years.
      Group 5 allergen levels were determined with a Phl p 5-specific ELISA in 2
      fractions of ambient air: particulate matter of greater than 10 MUm in diameter
      and particulate matter greater than 2.5 MUm and less than 10 MUm in diameter.
      Mediator release by ambient air was determined in FcepsilonRI-humanized
      basophils. The origin of pollen was modeled and condensed to pollen potency maps.
      RESULTS: On average, grass pollen released 2.3 pg of Phl p 5 per pollen. Allergen
      release per pollen (potency) varied substantially, ranging from less than 1 to 9
      pg of Phl p 5 per pollen (5% to 95% percentile). The main variation was locally
      day to day. Average potency maps across Europe varied between years. Mediator
      release from basophilic granulocytes correlated better with allergen levels per
      cubic meter (r(2) = 0.80, P < .001) than with pollen grains per cubic meter (r(2)
      = 0.61, P < .001). In addition, pollen released different amounts of allergen in
      the non-pollen-bearing fraction of ambient air, depending on humidity.
      CONCLUSION: Across Europe, the same amount of pollen released substantially
      different amounts of group 5 grass pollen allergen. This variation in allergen
      release is in addition to variations in pollen counts. Molecular aerobiology (ie,
      determining allergen in ambient air) might be a valuable addition to pollen
      counting.

PMID- 25956509
TI  - Different IgE recognition of mite allergen components in asthmatic and
      nonasthmatic children.
AB  - BACKGROUND: House dust mites (HDMs) represent one of the most important inducers
      of respiratory allergies worldwide. OBJECTIVE: We sought to investigate the IgE
      and IgG reactivity profiles to a comprehensive panel of HDM allergens in children
      with allergic asthma and to compare them with those of nonasthmatic atopic
      children. METHODS: Sera from clinically well-characterized asthmatic children
      with HDM allergy (n = 105), nonasthmatic children (n = 53), and nonatopic
      nonasthmatic children (n = 53) were analyzed for IgE and IgG reactivity to a
      panel of 7 HDM allergens (nDer p 1, rDer p 2, rDer p 5, rDer p 7, rDer p 10, rDer
      p 21, and rDer p 23) by means of allergen microarray technology. RESULTS:
      Asthmatic children with HDM allergy more frequently showed an IgE response to
      each of the HDM allergens and recognized more allergens than nonasthmatic
      children with HDM allergy. Furthermore, IgE levels to certain HDM allergens (nDer
      p 1, P = .002; rDer p 2, P = .007; rDer p 5, P = .031; and rDer p 23, P < .001)
      were significantly higher in asthmatic children than in children without asthma.
      By contrast, fewer asthmatic children showed IgG reactivity to HDM allergens than
      nonasthmatic children, but allergen-specific IgG levels were comparable.
      CONCLUSION: The IgE and IgG reactivity profiles to HDM allergens, as well as IgE
      levels to certain allergen components, differed considerably between children
      with and without asthmatic symptoms caused by HDM allergy. In fact, asthmatic
      children were characterized by an expanded IgE repertoire regarding the numbers
      of recognized allergen components and by increased specific IgE levels.

PMID- 25956511
TI  - Hypoxia-Inducible Factor-2alpha Limits Natural Killer T Cell Cytotoxicity in
      Renal Ischemia/Reperfusion Injury.
AB  - Natural killer T (NKT) cells are the major early-acting immune cell type and
      fundamental immune modulators in ischemia-reperfusion injury (IRI). Because
      lymphocytes are exposed to various oxygen tensions under pathophysiologic
      conditions, we hypothesize that hypoxia-inducible factors (HIFs) have roles in
      NKT cell activation, and thus determine the final outcome of renal IRI. In this
      study, we used Lck-Cre transgenic mice to specifically disrupt HIF-2alpha in
      T/NKT cells and found that HIF-2alpha knockout led to upregulated Fas ligand
      expression on peripheral NKT cells, but not on conventional T cells. HIF-2alpha
      knockout promoted infiltration of NKT cells into ischemic kidneys and exacerbated
      IRI, which could be mitigated by in vivo NK1.1(+) cell depletion or Fas ligand
      blockade. Compared with wild-type NKT cells, HIF-2alpha(-/-) NKT cells adoptively
      transferred to Rag1-knockout mice elicited more severe renal injury, and these
      mice were not protected by CGS21680, an adenosine A2A receptor agonist.
      Mechanistically, hypoxia-induced expression of adenosine A2A receptor in NKT
      cells and CGS21680-induced cAMP production in thymocytes were HIF-2alpha
      dependent. Hydrogen peroxide-induced Fas ligand expression on thymic wild-type
      NKT cells was significantly attenuated by CGS21680 treatment, but this effect was
      lost in HIF-2alpha(-/-) NKT cells. Finally, CGS21680 and LPS, an inducer of HIF
      2alpha in endothelium, synergistically reduced renal IRI substantially, but this
      effect was absent in Mx1-Cre-induced global HIF-2alpha-knockout mice. Taken
      together, our results reveal a hypoxia/HIF-2alpha/adenosine A2A receptor axis
      that restricts NKT cell activation when confronted with oxidative stress and thus
      protects against renal IRI. 

PMID- 25956510
TI  - Proteinase 3-ANCA Vasculitis versus Myeloperoxidase-ANCA Vasculitis.
AB  - In patients with GN or vasculitis, ANCAs are directed against proteinase 3 (PR3)
      or myeloperoxidase (MPO). The differences between PR3-ANCA-associated vasculitis
      (AAV) and MPO-AAV described in the past have been supplemented during the last
      decade. In this review, we discuss the differences between these two small-vessel
      vasculitides, focusing especially on possible etiologic and pathophysiologic
      differences. PR3-AAV is more common in northern parts of the world, whereas MPO
      AAV is more common in southern regions of Europe, Asia, and the Pacific, with the
      exception of New Zealand and Australia. A genetic contribution has been
      extensively studied, and there is a high prevalence of the HLA-DPB1*04:01 allele
      in patients with PR3-AAV as opposed to patients with MPO-AAV and/or healthy
      controls. Histologically, MPO-AAV and PR3-AAV are similar but show qualitative
      differences when analyzed carefully. Clinically, both serotypes are difficult to
      distinguish, but quantitative differences are present. More organs are affected
      in PR3-AAV, whereas renal limited vasculitis occurs more often in patients with
      MPO-AAV. For future clinical trials, we advocate classifying patients by ANCA
      serotype as opposed to the traditional disease type classification. 

PMID- 25956512
TI  - Role of NF-kappaB activation and VEGF gene polymorphisms in VEGF up regulation in
      non-proliferative and proliferative diabetic retinopathy.
AB  - The present study was aimed to investigate the relation between nuclear factor
      kappa beta (NFkappaB) activation and downstream up-regulation of vascular
      endothelial growth factor (VEGF) in diabetic retinopathy (DR). Moreover the study
      was intended to evaluate the role of VEGF gene single nucleotide polymorphisms
      (SNPs) in DR occurrence and to investigate the functional relevance of VEGF gene
      SNPs in terms of VEGF expression in DR. Serum level of VEGF, VEGF R1 (receptor
      1), VEGF R 2 (receptor 2) and NFkappaB (p50/65) activity was measured by enzyme
      linked immune sorbent assay. Genotyping and allelic composition of different SNPs
      i.e., rs2010963, rs3025039, rs1570360 and rs 2071559 were investigated by Taqman
      SNP genotyping assay. VEGF, NFkappaB p50/p65, and VEGF R1 & R2 gene expressions
      were quantified by real time quantitative polymerase chain reaction. Increased
      NFkappaB p50/p65 activity and expressions were observed in non proliferative
      diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) subjects
      compared to type 2 diabetes mellitus without retinopathy (DNR) group.
      Significantly elevated levels of serum VEGF and highest VEGF expression were
      found among PDR subjects compared to DNR or NPDR subjects. CC genotype and C
      allele of rs2010963 and TT genotype and T allele of rs3025039 were significantly
      over represented among PDR subjects compared to DNR group. Increased activation
      of NFkappabeta in NPDR and PDR subjects might involve increased up regulation of
      VEGF. VEGF SNPs i.e., rs2010963 C allele and rs3025039 T allele might be
      associated with PDR occurrence and in turn regulates VEGF expression among PDR
      subjects.

PMID- 25956514
TI  - Differential responses of C3 and CAM native Brazilian plant species to a SO2- and
      SPMFe-contaminated Restinga.
AB  - Aiming to evaluate responses in terms of growth rates, physiological parameters,
      and degree of sensitivity to SO2 and SPMFe in Eugenia uniflora L. (Myrtaceae, a
      C3 species) and Clusia hilariana Schlecht (Clusiaceae, a CAM species); saplings
      were exposed to emissions from a pelletizing factory for 7 months. The species
      were distributed along a transect (200, 500, 800, 1400, and 1700 m away from the
      emission source), and analyses were performed after 71, 118, and 211 days of
      exposure to the pollutants. E. uniflora received higher superficial deposition of
      particulate iron. The highest total iron foliar contents were observed 200 m away
      from the emission source in both plant species, while the highest total sulfur
      foliar contents were observed 200 m away in C. hilariana and 800 m away in E.
      uniflora. E. uniflora presented decreased values of height growth rate, number of
      necrotic leaves, chlorophyll analysis (SPAD index) and transpiration, in relation
      to the distances from the emission source. C. hilariana showed decreased values
      of height growth rate, number of leaves, number of necrotic leaves, total ionic
      permeability, stomatal conductance, transpiration, net CO2 assimilation, and
      total dry matter, in relation to distances from the emission source. In relation
      to the days of exposure, both species presented increased number of necrotic
      leaves and foliar phytotoxicity index, and decreased values in the chlorophyll
      analysis. The two native plant species, both of which occur in the Brazilian
      Restinga, showed damage when exposed to emissions from an iron ore pelletizing
      factory. C. hilariana was considered the most sensitive species due to the
      decreased values in a higher number of variables after exposition. 

PMID- 25956515
TI  - Evaluation of the pollution and human health risks posed by heavy metals in the
      atmospheric dust in Ebinur Basin in Northwest China.
AB  - Recently, a large amount of research assessing pollution levels and the related
      health risks posed by atmosphere dust has been undertaken worldwide. However,
      little work has been done in the oases of the arid regions of Northwest China. In
      this paper, we studied the pollution and health risks over a year of seven heavy
      metals in the atmospheric dust of Ebinur Basin, a typical oasis in Northwest
      China. The results showed the following: (1) The annual amount of atmospheric
      deposition in Ebinur Basin was 298.23 g m(-2) and the average monthly atmospheric
      deposition was 25.06 g m(-2). The average and maximum values of the seven heavy
      metals measured were all below the National Soil Environmental Quality Standards
      (2nd). (2) Heavy metals of Cu, Cr, and As in the atmospheric deposition mainly
      originated from the natural geological background, while Zn came from human
      activity. This study also showed that among the seven measured heavy metals, the
      ratios of the no-pollution status of Pb, Cd, and Hg were higher than those of
      others with moderate degrees of pollution also accounting for a certain ratio.
      (3) The carcinogenic risks from As, Cd, and Cr were all lower than the
      corresponding standard limit values, and these metals are considered not harmful
      to the health of the basin. However, there is a relatively high risk of exposure
      for children from hand-to-mouth intake, which is worthy of attention. This
      research showed that both human activity and natural factors, such as wind and
      altitude, influenced the heavy metal contents in the atmospheric dust of the
      study area. Furthermore, recent human activity in the study area had the most
      negative influence on the accumulation of the heavy metals and the corresponding
      health risks, especially for Hg, Pb, and Cd, which is worthy of attention. 

PMID- 25956513
TI  - Emerging and priority contaminants with endocrine active potentials in sediments
      and fish from the River Po (Italy).
AB  - There is a substantial lack of information on most priority pollutants, related
      contamination trends, and (eco)toxicological risks for the major Italian
      watercourse, the River Po. Targeting substances of various uses and origins, this
      study provides the first systematic data for the River Po on a wide set of
      priority and emerging chemicals, all characterized by endocrine-active
      potentials. Flame retardants, natural and synthetic hormones, surfactants,
      personal care products, legacy pollutants, and other chemicals have been
      investigated in sediments from the River Po and its tributary, the River Lambro,
      as well as in four fish species from the final section of the main river. With
      few exceptions, all chemicals investigated could be tracked in the sediments of
      the main Italian river for tens or hundreds of kilometres downstream from the
      Lambro tributary. Nevertheless, the results indicate that most of these
      contaminants, i.e., TBBPA, TCBPA, TBBPA-bis, DBDPE, HBCD, BPA, OP, TCS, TCC,
      AHTN, HHCB, and DDT, individually pose a negligible risk to the River Po. In
      contrast, PBDE, PCB, natural and synthetic estrogens, and to a much lower extent
      NP, were found at levels of concern either to aquatic life or human health.
      Adverse biological effects and prohibition of fish consumption deserve research
      attention and management initiatives, also considering the transport of
      contaminated sediments to transitional and coastal environments of the Italian
      river. 

PMID- 25956516
TI  - Combined removal of a BTEX, TCE, and cis-DCE mixture using Pseudomonas sp.
      immobilized on scrap tyres.
AB  - The simultaneous aerobic removal of a mixture of benzene, toluene, ethylbenzene,
      and o,m,p-xylene (BTEX); cis-dichloroethylene (cis-DCE); and trichloroethylene
      (TCE) from the artificially contaminated water using an indigenous bacterial
      isolate identified as Pseudomonas plecoglossicida immobilized on waste scrap
      tyres was investigated. Suspended and immobilized conditions were compared for
      the removal of these volatile organic compounds. For the immobilized system,
      toluene, benzene, and ethylbenzene were completely removed, while the highest
      removal efficiencies of 99.0 +/- 0.1, 96.8 +/- 0.3, 73.6 +/- 2.5, and 61.6 +/-
      0.9% were obtained for o-xylene, m,p-xylene, TCE, and cis-DCE, respectively. The
      sorption kinetics of contaminants towards tyre surface was also evaluated, and
      the sorption capacity generally followed the order of toluene > benzene > m,p
      xylene > o-xylene > ethylbenzene > TCE > cis-DCE. Scrap tyres showed a good
      capability for the simultaneous sorption and bioremoval of BTEX/cis-DCE/TCE
      mixture, implying a promising waste material for the removal of contaminant
      mixture from industrial wastewater or contaminated groundwater.

PMID- 25956517
TI  - Potential of Ranunculus acris L. for biomonitoring trace element contamination of
      riverbank soils: photosystem II activity and phenotypic responses for two soil
      series.
AB  - Foliar ionome, photosystem II activity, and leaf growth parameters of Ranunculus
      acris L., a potential biomonitor of trace element (TE) contamination and
      phytoavailability, were assessed using two riverbank soil series. R. acris was
      cultivated on two potted soil series obtained by mixing a TE (Cd, Cu, Pb, and Zn)
      contaminated technosol with either an uncontaminated sandy riverbank soil (A) or
      a silty clay one slightly contaminated by TE (B). Trace elements concentrations
      in the soil-pore water and the leaves, leaf dry weight (DW) yield, total leaf
      area (TLA), specific leaf area (SLA), and photosystem II activity were measured
      for both soil series after a 50-day growth period. As soil contamination
      increased, changes in soluble TE concentrations depended on soil texture.
      Increase in total soil TE did not affect the leaf DW yield, the TLA, the SLA, and
      the photosystem II activity of R. acris over the 50-day exposure. The foliar
      ionome did not reflect the total and soluble TE concentrations in both soil
      series. Foliar ionome of R. acris was only effective to biomonitor total and
      soluble soil Na concentrations in both soil series and total and soluble soil Mo
      concentrations in the soil series B. 

PMID- 25956518
TI  - Improvement in phytoremediation potential of Solanum nigrum under cadmium
      contamination through endophytic-assisted Serratia sp. RSC-14 inoculation.
AB  - The growth of hyperaccumulator plants is often compromised by increased toxicity
      of metals like cadmium (Cd). However, extraction of such metals from the soil can
      be enhanced by endophytic microbial association. Present study was aimed to
      elucidate the potential of microbe-assisted Cd phytoextraction in
      hyperaccumulator Solanum nigrum plants and their interactions under varied Cd
      concentrations. An endophytic bacteria Serratia sp. RSC-14 was isolated from the
      roots of S. nigrum. In addition to Cd tolerance up to 4 mM, the RSC-14 exhibited
      phosphate solubilization and secreted plant growth-promoting phytohormones such
      as indole-3-acetic acid (54 MUg/mL). S. nigrum plants were inoculated with RSC-14
      and were grown in different concentrations of Cd (0, 10, and 30 mg Cd kg(-1)
      sand). Results revealed that Cd treatment caused significant cessation in plant
      growth, biomass, and chlorophyll content, whereas significantly higher
      malondialdehyde (MDA) and electrolyte production in leaves were observed in a
      dose-dependent manner. Conversely, RSC-14 inoculation relived the toxic effects
      of Cd-induced stress by significantly increasing root/shoot growth, biomass
      production, and chlorophyll content and decreasing MDA and electrolytes contents.
      Ameliorative effects on host growth were also observed by the regulation of metal
      induced oxidative stress enzymes such as catalase, peroxidase, and polyphenol
      peroxidase. Activities of these enzymes were significantly reduced in RSC-14
      inoculated plants as compared to control plants under Cd treatments. The lower
      activities of stress responsive enzymes suggest modulation of Cd stress by RSC
      14. The current findings support the beneficial uses of Serratia sp. RSC-14 in
      improving the phytoextraction abilities of S. nigrum plants in Cd contamination. 

PMID- 25956519
TI  - National monitoring of nicotine use in Czech and Slovak Republic based on
      wastewater analysis.
AB  - The aim of this study was to compare estimation of nicotine use in Slovakia (SR)
      and the Czech Republic (CR) based on cotinine analysis in wastewater from seven
      selected wastewater treatment plants (WWTPs) with conventional estimation based
      on tobacco product sales. Urinary bio-markers of nicotine use were analyzed by
      liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The study
      was performed concurrently at all the WWTPs (from 11 to 18 March 2014).
      Representative 24 h composite samples were analyzed with on line SPE/LC-MS/MS
      method. Based on the average residence time of wastewater in the sewers and the
      average time in the sampling device, specific correction coefficients were
      designed to improve estimation of nicotine consumption. Nicotine ingestion level
      was back-calculated and expressed as mass of pure drug consumed per day and per
      1000 inhabitants for selected cities of both countries (mean, 2.2 g for Piestany
      and 8.0 g for Nitra, respectively). Consequently, the cigarette consumption
      results were recalculated for each country separately and compared with the data
      of both national statistical offices (2362 cigarettes/year/person--SR and 2088
      cigarettes/year/person--CR). Our results highly correspond to the data of
      national statistical offices (up to 99.9% in SR and to 96% in CR). The average
      amount of money invested in cigarette sales was estimated in the capitals of both
      countries. It is about 1 million EUR/day for Prague and about 0.3 million EUR/day
      for Bratislava. The calculation of nicotine consumption, utilizing a specific
      correction coefficient, is the correct way to obtain more accurate data in drug
      studies of this kind, thus allowing a better drug abuse assessment.

PMID- 25956520
TI  - Laparoscopic versus open wedge resection for gastrointestinal stromal tumors of
      the stomach: a single-center 8-year retrospective cohort study of 156 patients
      with long-term follow-up.
AB  - BACKGROUND: The aim of this study was to compared laparoscopic (LWR) and open
      wedge resection (OWR) for the treatment of gastric gastrointestinal stromal
      tumors (GISTs). METHODS: The data of 156 consecutive GISTs patients underwent LWR
      or OWR between January 2006 and December 2013 were collected retrospectively. The
      surgical outcomes and the long-term survival rates were compared. Besides, a
      rapid systematic review and meta-analysis were conducted. RESULTS:
      Clinicopathological characteristics of the patients were similar between the two
      groups. The LWR group was associated with less intraoperative blood loss (67.3
      vs. 142.7 ml, P < 0.001), earlier postoperative flatus (2.3 vs. 3.2 days, P <
      0.001), earlier oral intake (3.2 vs. 4.1 days, P < 0.001) and shorter
      postoperative hospital stay (6.0 vs. 8.0 days, P = 0.001). The incidence of
      postoperative complications was lower in LWR group but did not reach statistical
      significance (4/90, 4.4% vs. 8/66, 12.1%, P = 0.12). No significant difference
      was observed in 3-year relapse-free survival rate between the two groups (98.6%
      vs. 96.4%, P > 0.05). The meta-analysis revealed similar results except less
      overall complications in the LWR group (RR = 0.49, 95% CI, 0.25 to 0.95, P =
      0.04). And the recurrence risk was similar in two group (RR = 0.80, 95% CI, 0.28
      to 2.27, P > 0.05). CONCLUSIONS: LWR is a technically and oncologically safe and
      feasible approach for gastric GISTs compared with OWR. Moreover, LWR appears to
      be a preferable choice with mini-invasive benefits.

PMID- 25956521
TI  - The Ll.LtrB intron from Lactococcus lactis excises as circles in vivo: insights
      into the group II intron circularization pathway.
AB  - Group II introns are large ribozymes that require the assistance of intron
      encoded or free-standing maturases to splice from their pre-mRNAs in vivo. They
      mainly splice through the classical branching pathway, being released as RNA
      lariats. However, group II introns can also splice through secondary pathways
      like hydrolysis and circularization leading to the release of linear and circular
      introns, respectively. Here, we assessed in vivo splicing of various constructs
      of the Ll.LtrB group II intron from the Gram-positive bacterium Lactococcus
      lactis. The study of excised intron junctions revealed, in addition to branched
      intron lariats, the presence of perfect end-to-end intron circles and
      alternatively circularized introns. Removal of the branch point A residue
      prevented Ll.LtrB excision through the branching pathway but did not hinder
      intron circle formation. Complete intron RNA circles were found associated with
      the intron-encoded protein LtrA forming nevertheless inactive RNPs. Traces of
      double-stranded head-to-tail intron DNA junctions were also detected in L. lactis
      RNA and nucleic acid extracts. Some intron circles and alternatively circularized
      introns harbored variable number of non-encoded nucleotides at their splice
      junction. The presence of mRNA fragments at the splice junction of some intron
      RNA circles provides insights into the group II intron circularization pathway in
      bacteria. 

PMID- 25956523
TI  - A Cannulated Tri-Tapered Femoral Stem for Total Hip Arthroplasty: Clinical and
      Radiological Results at Ten Years.
AB  - We report the ten-year clinical and radiological outcomes of a novel cannulated,
      tri-tapered femoral stem, used in primary total hip arthroplasty (110 stems in 98
      patients). At ten years, two Tri-taper stems had been revised for infection and
      dislocation. The mean Oxford Hip Score improved from 13.46 pre-operatively, to
      37.04. Radiological analysis revealed radiolucent lines in 57 cases, but none
      exceeded 2 mm thickness. Stem subsidence was identified in 63 cases, with mean
      distal tip migration of 3.8 mm. Survivorship with revision for aseptic loosening
      as the end point was 100% at 10 years. Stem survival with revision for any cause
      was 98.2% (95% CI, 92.9% to 99.5%). The ten-year results of the Tri-taper stem
      are comparable to other polished, tapered femoral stems.

PMID- 25956522
TI  - Difference in Stem Alignment Between the Direct Anterior Approach and the
      Posterolateral Approach in Total Hip Arthroplasty.
AB  - The purpose of this study was to investigate the effects of different surgical
      approaches, the posterolateral approach (PLA) and the direct anterior approach
      (DAA), on postoperative femoral anteversion and stem coronal and sagittal
      alignment in total hip arthroplasty (THA), and to identify the factors related to
      postoperative femoral anteversion and stem alignment. A total of 209 hips of 181
      patients were evaluated. THA was performed through the PLA in 80 hips and through
      the DAA in 129 hips. Femoral anteversion and stem alignment were measured on
      postoperative computed tomography images. The factor related to postoperative
      anteversion change was preoperative femoral anteversion, and the surgical
      approaches did not affect the postoperative anteversion change, while surgical
      approach did have an effect on stem sagittal alignment. 

PMID- 25956524
TI  - The Outcome of 241 Charnley Total Hip Arthroplasties Performed by One Surgeon 30
      to 40 Years Ago.
AB  - We present the outcome of 241 consecutive low friction arthroplasties (LFAs)
      performed by one surgeon (GH) 30 to 40 years ago. The overall survival rate at 30
      years with revision for any reason or removal of the components as the end point
      was 53% (43.2-62.8%) when 40 hips remained in the study. Cox regression analysis
      for the possible risk factors of age, gender and diagnosis revealed higher risk
      of the overall failure in younger patients, and higher risk of failure due to
      loosening in younger patients and in those with congenital hip disease. Our
      follow-up study at 30 to 40 years following Charnley LFA can be used as a
      benchmark for comparison with the newer methods of total hip arthroplasty.

PMID- 25956525
TI  - MRI Based Comparison of Tibial Bone Coverage by Five Knee Prosthesis:
      Anthropometric Study in Indians.
AB  - This MRI based study evaluates morphological differences of proximal tibia (total
      cross-sectional area, mediolateral and anteroposterior distance) 8-10 mm distal
      to the lateral tibial plateau. We evaluated the difference in the coverage of the
      tibial surface between symmetric and asymmetric tibial trays and difference in
      coverage between males and females. 150 patients who underwent MRI scans for
      sports related soft tissue injury without osteoarthritis were studied. The tibial
      trays of the 5 total knee arthroplasty designs (4 symmetric and 1 asymmetric)
      were scanned. Mean total tibial coverage of all designs was more than 80%.
      Asymmetric baseplate had maximum total tibial coverage and maximum rate of
      optimal fit, with only 2% absolute overhang posterolaterally. Females had better
      tibial coverage as compared to males. 

PMID- 25956526
TI  - Revision of Articular Surface Replacement (ASR) Total Hip Arthroplasty:
      Correlation of Perioperative Data and Early Post-Revision Outcome Results.
AB  - The articular surface replacement (ASR) total hip arthroplasty (THA) showed
      accelerated failure rates due to adverse-reaction to metal debris (ARMD).
      Literature correlating preoperative with intraoperative revision findings
      respectively post-revision outcome results are rare. 30 of 99 available ASR THA
      were revised due to ARMD. Mean post-revision follow-up term was 2.3 years. In
      part, preoperative data did not correlate with intraoperative revision findings.
      ARMD was even found in asymptomatic patients with non-elevated ion levels.
      Postoperative pain and metal ions decreased significantly (P <= 0.016). Cobalt
      decreased faster than chrome. Patients with intraoperative pseudotumors,
      osteolysis or bilateral THA did not have higher pre- or postoperative ion values
      (P >= 0.053). Females showed higher postoperative chrome levels (P=0.031). One
      major post-revision complication (femoral nerve palsy) and one re-revision (late
      onset infection) occurred.

PMID- 25956527
TI  - Identification of HECT E3 ubiquitin ligase family genes involved in stem cell
      regulation and regeneration in planarians.
AB  - E3 ubiquitin ligases constitute a large family of enzymes that modify specific
      proteins by covalently attaching ubiquitin polypeptides. This post-translational
      modification can serve to regulate protein function or longevity. In spite of
      their importance in cell physiology, the biological roles of most ubiquitin
      ligases remain poorly understood. Here, we analyzed the function of the HECT
      domain family of E3 ubiquitin ligases in stem cell biology and tissue
      regeneration in planarians. Using bioinformatic searches, we identified 17 HECT
      E3 genes that are expressed in the Schmidtea mediterranea genome. Whole-mount in
      situ hybridization experiments showed that HECT genes were expressed in diverse
      tissues and most were expressed in the stem cell population (neoblasts) or in
      their progeny. To investigate the function of all HECT E3 ligases, we inhibited
      their expression using RNA interference (RNAi) and determined that orthologs of
      huwe1, wwp1, and trip12 had roles in tissue regeneration. We show that huwe1 RNAi
      knockdown led to a significant expansion of the neoblast population and death by
      lysis. Further, our experiments showed that wwp1 was necessary for both neoblast
      and intestinal tissue homeostasis as well as uncovered an unexpected role of
      trip12 in posterior tissue specification. Taken together, our data provide
      insights into the roles of HECT E3 ligases in tissue regeneration and demonstrate
      that planarians will be a useful model to evaluate the functions of E3 ubiquitin
      ligases in stem cell regulation. 

PMID- 25956528
TI  - Ten Mistakes To Avoid When Injecting Botulinum Toxin.
AB  - Injection of botulinum toxin is currently the most common cosmetic procedure in
      the United States, and in recent years it has become-together with dermal fillers
      the mainstay of therapy for the prevention and treatment of facial aging.
      However, in some cases the treatment may lead to a somewhat unnatural appearance,
      usually caused by loss of facial expression or other telltale signs. In the
      present article, we review the 10 mistakes that should be avoided when injecting
      botulinum toxin. We also reflect on how treatment with botulinum toxin influences
      us through our facial expressions, both in terms of how we feel and what others
      perceive. 

PMID- 25956529
TI  - Current understanding of the pathophysiology of systemic juvenile idiopathic
      arthritis (sJIA) and target-directed therapeutic approaches.
AB  - Because of its distinct clinical and laboratory features, reflecting systemic
      inflammation, sJIA can be distinguished from other forms of JIA which usually
      present as a milder phenotype. The exact pathophysiology of sJIA, however,
      remains unknown. Profound dysregulation of innate pro- and anti-inflammatory
      cytokines, and rapid clinical response to cytokine blocking strategies in sJIA
      patients suggest impaired control mechanisms in innate immune cells contributing
      to sJIA pathogenesis. Endogenous TLR ligands, such as S100 protein complexes,
      enhance the pro-inflammatory phenotype. Associations with polymorphisms in
      cytokine genes and their receptors suggest a genetic component. Furthermore,
      genetic associations that have been reported in familial hemophagocytic
      lympohistiocytosis also exist in patients with sJIA-associated macrophage
      activation syndrome, a severe complication of sJIA. Reported mutations in single
      genes, however, are too weak to confer sJIA, suggesting a multi-factorial mode of
      inheritance. We provide an overview of current pathophysiological concepts, state
      of-the-art treatment regimens, and unanswered questions in sJIA. 

PMID- 25956530
TI  - A case of XMEN syndrome presented with severe auto-immune disorders mimicking
      autoimmune lymphoproliferative disease.

PMID- 25956532
TI  - [Management of complications of fissure and fistula surgery].
AB  - BACKGROUND: Fistula-in-ano and anal fissures are common proctological diseases.
      In most cases of anal fissures conservative treatment provides good clinical
      results, whereas for fistula-in-ano operative treatment is the only option.
      OBJECTIVE: The most important and for the patient most stressful long-term
      complication is postoperative incontinence, especially as the deliberate
      severance of the anal sphincter musculature is part of the treatment for many
      patients. In this article the causes and treatment options are discussed.
      RESULTS: The therapy of choice for patients with persisting symptoms caused by an
      anal fissure is fissurectomy. Incontinence disorders develop due to severance of
      parts of the internal sphincter or resection of the anoderm. In patients with
      anal fistulas the occurrence of incontinence disorders depends on the anatomical
      relationship of the fistula to the sphincter, the surgical procedure and also on
      pre-existing damage, e.g. from childbirth or other sphincter trauma and scar
      formation, notably in patients with multiple surgical interventions. Severance of
      the sphincter muscles in proximal transsphincteric and suprasphincteric fistulas
      in particular bears a high risk of postoperative incontinence. Data from the
      literature regarding postoperative fecal incontinence vary enormously due to
      different follow-up intervals and also variable definitions of the term fecal
      incontinence. CONCLUSION: Options for the treatment of postoperative fecal
      incontinence are limited. Treatment of postoperative incontinence should first be
      conservative. Surgical repair of damaged sphincter muscles is often of limited
      success and sacral nerve stimulation might be an option in selected patients.
      Especially in patients with fissure-in-ano the indications for surgery should be
      strictly adhered to. For fistula-in-ano the least invasive and most sphincter
      preserving procedure should be selected.

PMID- 25956533
TI  - Bone status of Indian children and adolescents with type 1 diabetes mellitus.
AB  - OBJECTIVE: Low bone mineral density has been reported in children and adolescents
      with type 1 diabetes (T1DM). The aims of this cross-sectional study were to study
      growth, serum IGF1 concentrations and bone health parameters assessed by Dual
      Energy X-ray Absorptiometry (DXA). METHODS: Height was measured and converted to
      Z scores (HAZ). Serum IGF1 concentrations were measured (ELISA) in a subset. Bone
      mineral content for total body (less head) (TBBMC) and lumbar spine was measured
      (n=170, 77 boys, 6-16years old) and converted to Z scores using local normative
      data. RESULT: Mean age was 11.1+/-3.8years, disease duration was 2.2+/-2.5years
      and HbA1C was 10.1+/-1.8%. Diabetic children were shorter than reference
      population (HAZ -0.6+/-1.1); Z scores for height and total body bone area (TBBA)
      for height were <-2SD in 12% & 6% respectively. Serum IGF1 Z scores were lower
      amongst group with longer disease duration (-1.58+/-1.3 vs -2.63+/-0.7; P=0.037).
      Disease duration (beta=-0.180, P=0.000) and metabolic control (HbA1C; beta=
      0.096, P=0.042) were negative predictors of HAZ and TBBA for height Z in younger
      children. Using the Molgaard approach, children with longer disease duration had
      lower HAZ (-0.31+/-0.92 vs -1.28+/-1.11; P=0.000; "short bones") and TBBA for
      height Z scores (0.12+/-1.62 vs -0.53+/-0.94; P=0.044; "slender bones"). Older
      children (tanner stages 4 and 5) had lower BMC and BA as compared to reference
      population possibly due to delayed growth spurt. CONCLUSION: Longer duration of
      diabetes was associated with shorter and slender but appropriately mineralized
      bones. Small and slender bones in diabetic children may increase risk of
      fragility fractures in the future. This article is part of a Special Issue
      entitled "Bone and diabetes".

PMID- 25956531
TI  - The gut microbiome in autoimmunity: Sex matters.
AB  - Autoimmune diseases like rheumatoid arthritis are multifactorial in nature,
      requiring both genetic and environmental factors for onset. Increased
      predisposition of females to a wide range of autoimmune diseases points to a
      gender bias in the multifactorial etiology of these disorders. However, the
      existing evidence to date has not provided any conclusive mechanism of gender
      bias beyond the role of hormones and sex chromosomes. The gut microbiome, which
      impacts the innate and adaptive branches of immunity, not only influences the
      development of autoimmune disorders but may interact with sex-hormones to
      modulate disease progression and sex-bias. Here, we review the current
      information on gender bias in autoimmunity and discuss the potential of
      microbiome-derived biomarkers to help unravel the complex interplay between
      genes, environment and hormones in rheumatoid arthritis.

PMID- 25956534
TI  - 5-Fluoruracil blocked giant cell tumor progression by suppressing
      osteoclastogenesis through NF-kappaB signals and blocking angiogenesis.
AB  - Giant cell tumor of bone (GCTB) is a bone destroying tumor comprised of spindle
      like stromal cells and monocytes of myeloid lineage that are differentiated into
      osteoclast-like multinucleated giant cells. Nuclear factor-Kappa B (NF-kappaB)
      has been identified to be essential for GCT progression. Herein, we found that 5
      Fluorouracil (5-FU), a widely used chemotherapeutics, is a promising anticancer
      agent for GCT both targeting spindle-like stromal cells and osteoclast giant
      cells through NF-kappaB pathway. In this study, in vitro 5-FU not only directly
      blocked both stromal cell- and RANKL-induced osteoclastogenesis through NF-kappaB
      pathway, but also indirectly inhibited osteoclast formation and angiogenesis by
      suppressing the expression of osteoclast-activating factors including IL-1beta,
      MCP-1 and tumor angiogenesis factor VEGF in stromal cells. In vivo, we found that
      5-FU blocked GCT progression through NF-kappaB pathway by utilizing our chick
      embryo chorioallantoic membrane (CAM) model. Taken together, our results suggest
      that 5-FU can inhibit GCT development by suppressing osteoclast formation through
      NF-kappaB pathway and blocking angiogenesis, and may serve as a novel agent in
      the treatment of GCT. 

PMID- 25956535
TI  - Efficient soluble expression of active recombinant human cyclin A2 mediated by E.
      coli molecular chaperones.
AB  - Bacterial expression of human proteins continues to present a critical challenge
      in protein crystallography and drug design. While human cyclin A constructs have
      been extensively characterized in complex with cyclin dependent kinase 2 (CDK2),
      efforts to express the monomeric human cyclin A2 in Escherichia coli in a stable
      form, without the kinase subunit, have been laden with technical difficulties,
      including solubility, yield and purity. Here, optimized conditions are described
      with the aim of generating for first time, sufficient quantities of human
      recombinant cyclin A2 in a soluble and active form for crystallization and ligand
      characterization purposes. The studies involve implementation of a His-tagged
      heterologous expression system under conditions of auto-induction and mediated by
      molecular chaperone-expressing plasmids. A high yield of human cyclin A2 was
      obtained in natively folded and soluble form, through co-expression with groups
      of molecular chaperones from E. coli in various combinations. A one-step affinity
      chromatography method was utilized to purify the fusion protein products to
      homogeneity, and the biological activity confirmed through ligand-binding
      affinity to inhibitory peptides, representing alternatives for the key
      determinants of the CDK2 substrate recruitment site on the cyclin regulatory
      subunit. As a whole, obtaining the active cyclin A without the CDK partner
      (referred to as monomeric in this work) in a straightforward and facile manner
      will obviate protein--production issues with the CDK2/cyclin A complex and enable
      drug discovery efforts for non-ATP competitive CDK inhibition through the cyclin
      groove.

PMID- 25956536
TI  - Construction and development of a novel expression system of Streptomyces.
AB  - Streptomyces is well known to be an attractive host for producing large amounts
      of proteins with potent biological activities into the culture supernatant. To
      expand its expression system, we constructed a novel expression plasmid for gene
      expression in Streptomyces by inserting the promoter (P(tg)) and the signal
      peptide (SP(tg)) of transglutaminase (TGase) from Streptomyces hygroscopicus
      WSH03-13 into vector pIJ86, followed by multiple cloning sites and a
      transcriptional terminator fd (fd-ter). The secretion capacity of the vector was
      further enhanced by optimizing the signal peptidase cleavage site and a rare
      codon of SP(tg), yielding expression vector pSG02. Using this vector, TGase was
      actively and greatly expressed in the supernatant in several Streptomyces
      strains. In addition, the heterologous proteins aminopeptidase from Bacillus
      subtilis Zj016 (BSAP) and phenylalanine ammonia-lyase from Rhodotorula glutinis
      (PAL) were also expressed in various Streptomyces strains by this vector. This
      expression system should be useful for the expression of other proteins.

PMID- 25956537
TI  - The Impact of Endoscopic Inflammation and Mucosal Healing on Health-related
      Quality of Life in Ulcerative Colitis Patients.
AB  - BACKGROUND: Health-related quality of life [HRQoL] is impaired in ulcerative
      colitis and is correlated to clinical disease activity. The recent shift towards
      more objective treatment goals like mucosal healing generates a need for
      evaluating the association between endoscopic disease activity, mucosal healing
      and HRQoL. METHODS: In this cross-sectional study, patients with either active or
      inactive ulcerative colitis underwent sigmoidoscopy. Clinical disease activity
      was assessed by the Simple Clinical Colitis Activity Index [SCCAI], endoscopic
      inflammation by the Mayo Endoscopic Subscore [MES], and HRQoL by the Short
      Inflammatory Bowel Disease Questionnaire [SIBDQ] and Short Health Scale [SHS].
      RESULTS: A total of 110 patients, 71% with active disease, had a median SCCAI
      score of 3 and a median MES score of 1. Patients in clinical remission had a mean
      SIBDQ of 60 and SHS of 6. HRQoL decreased significantly with increasing clinical
      (SIBDQ [chi(2) = 61.8, p < 0.0001] and SHS [chi(2) = 63.4, p < 0.0001]) and
      endoscopic disease activity (SIBDQ [chi(2) = 33.1, p < 0.0001] and SHS [chi(2) =
      40.3, p < 0.0001]). Mucosal healing was associated with a higher HRQoL than
      active inflammation (59/46, p < 0.0001 [SIBDQ] and 7/20, p < 0.0001 [SHS]).
      Decreased HRQoL was observed with more extensive disease. Linear regression
      revealed strong association between SIBDQ and SHS. CONCLUSIONS: Not only clinical
      disease activity but also endoscopic inflammation and disease extent were
      associated with decreased HRQoL. Patients with mucosal healing had significant
      higher HRQoL, emphasising the importance of this treatment goal. Both SHS and
      SIBDQ are easy to use and to implement, and were strongly correlated.

PMID- 25956538
TI  - The Impact of Clinical Information on the Assessment of Endoscopic Activity:
      Characteristics of the Ulcerative Colitis Endoscopic Index Of Severity [UCEIS].
AB  - BACKGROUND AND AIMS: To determine whether clinical information influences
      endoscopic scoring by central readers using the Ulcerative Colitis Endoscopic
      Index of Severity [UCEIS; comprising 'vascular pattern', 'bleeding', 'erosions
      and ulcers']. METHODS: Forty central readers performed 28 evaluations, including
      2 repeats, from a library of 44 video sigmoidoscopies stratified by Mayo Clinic
      Score. Following training, readers were randomised to scoring with ['unblinded',
      n = 20, including 4 control videos with misleading information] or without
      ['blinded', n 20] clinical information. A total of 21 virtual Central Reader
      Groups [CRGs], of three blinded readers, were created. Agreement criteria were
      pre-specified. Kappa [kappa] statistics quantified intra- and inter-reader
      variability. RESULTS: Mean UCEIS scores did not differ between blinded and
      unblinded readers for any of the 40 main videos. UCEIS standard deviations [SD]
      were similar [median blinded 0.94, unblinded 0.93; p = 0.97]. Correlation between
      UCEIS and visual analogue scale [VAS] assessment of overall severity was high [r
      blinded = 0.90, unblinded = 0.93; p = 0.02]. Scores for control videos were
      similar [UCEIS: p >= 0.55; VAS: p >= 0.07]. Intra- [kappa 0.47-0.74] and inter
      reader [kappa 0.40-0.53] variability for items and full UCEIS was 'moderate'-to
      'substantial', with no significant differences except for intra-reader
      variability for erosions and ulcers [kappa blinded: 0.47 vs unblinded: 0.74; p
      0.047]. The SD of CRGs was lower than for individual central readers [0.54 vs
      0.95; p < 0.001]. Correlation between blinded UCEIS and patient-reported symptoms
      was high [stool frequency: 0.76; rectal bleeding: 0.82; both: 0.81]. CONCLUSIONS:
      The UCEIS is minimally affected by knowledge of clinical details, strongly
      correlates with patient-reported symptoms, and is a suitable instrument for
      trials. CRGs performed better than individuals.

PMID- 25956539
TI  - What is Disease Progression in Crohn's Disease and how can it be Measured?

PMID- 25956540
TI  - Efficacy of cilostazol on inhibition of platelet aggregation, inflammation and
      myonecrosis in acute coronary syndrome patients undergoing percutaneous coronary
      intervention: The ACCEL-LOADING-ACS (ACCELerated Inhibition of Platelet
      Aggregation, Inflammation and Myonecrosis by Adjunctive Cilostazol Loading in
      Patients With Acute Coronary Syndrome) study.

PMID- 25956541
TI  - Synergistic fungicidal activity of the lipopeptide bacillomycin D with
      amphotericin B against pathogenic Candida species.
AB  - In the present study, the synergism of the lipopeptide bacillomycin D in
      combination with the polyene amphotericin B against pathogenic Candida species is
      described along with their potential cytotoxicity against mammalian cells.
      Bacillomycin D inhibited the growth of various Candida species at minimal
      concentrations from 12.5 to 25 MUg ml(-1). Furthermore, it showed a synergistic
      effect with the antifungal drug amphotericin B in inhibiting the growth of
      Candida strains, with fractional inhibitory concentration indices ranging from
      0.28 to 0.5. Time killing studies revealed a >2-log reduction in the viability of
      Candida albicans ATCC 10231 cells after 3 h incubation with the combination
      amphotericin B plus bacillomycin D, at their subinhibitory concentration.
      Interestingly, when the two drugs were used together at those dosages displaying
      a synergism in the anti-Candida activity, no cytotoxic effect was observed
      against mammalian cells. Therefore, the combination bacillomycin D/amphotericin B
      may represent a valid alternative to conventional antifungals for topical
      treatment of C. albicans infections. To the best of our knowledge, this is the
      first report describing the in vitro interaction between the antifungal drug
      amphotericin B and bacillomycin D against pathogenic Candida species. 

PMID- 25956542
TI  - Dekkera bruxellensis--spoilage yeast with biotechnological potential, and a model
      for yeast evolution, physiology and competitiveness.
AB  - Dekkera bruxellensis is a non-conventional yeast normally considered a spoilage
      organism in wine (off-flavours) and in the bioethanol industry. But it also has
      potential as production yeast. The species diverged from Saccharomyces cerevisiae
      200 mya, before the whole genome duplication. However, it displays similar
      characteristics such as being Crabtree- and petite positive, and the ability to
      grow anaerobically. Partial increases in ploidy and promoter rewiring may have
      enabled evolution of the fermentative lifestyle in D. bruxellensis. On the other
      hand, it has genes typical for respiratory yeasts, such as for complex I or the
      alternative oxidase AOX1. Dekkera bruxellensis grows more slowly than S.
      cerevisiae, but produces similar or greater amounts of ethanol, and very low
      amounts of glycerol. Glycerol production represents a loss of energy but also
      functions as a redox sink for NADH formed during synthesis of amino acids and
      other compounds. Accordingly, anaerobic growth required addition of certain amino
      acids. In spite of its slow growth, D. bruxellensis outcompeted S. cerevisiae in
      glucose-limited cultures, indicating a more efficient energy metabolism and/or
      higher affinity for glucose. This review tries to summarize the latest
      discoveries about evolution, physiology and metabolism, and biotechnological
      potential of D. bruxellensis. 

PMID- 25956543
TI  - Tissue PAH, blood cell and tissue changes following exposure to water
      accommodated fractions of crude oil in alligator gar, Atractosteus spatula.
AB  - Alligator gar Atractosteus spatula acclimated to brackish water (9 ppt) were
      exposed to water accommodated fraction oil loadings (surrogate to Macondo
      Deepwater Horizon, northern Gulf of Mexico) of 0.5 and 4.0 gm oil/L tank water
      for 48 h. The surrogate oil was approximately 98% alkanes and alkynes and 2%
      petroleum aromatic hydrocarbons. The 2% petroleum aromatic hydrocarbons were
      predominately naphthalene. After 48 h, naphthalene levels in fish liver exposed
      to 0.5 or 4 gm oil/L were 547.79 and 910.68 ppb, while muscle levels were 214.11
      and 253.84 ppb. There was a significant decrease in peripheral blood lymphocyte
      numbers and a significant reduction of granulocytes in the kidney marrow of the
      same fish. Tissue changes included hepatocellular vacuolization and necrosis,
      necrotizing pancreatitis, renal eosinophilia, and splenic congestion. After 7
      days recovery, liver naphthalene levels decreased to 43.59 and 43.20 ppb, while
      muscle levels decreased to 9.74, and 16.78 ppb for oil exposures of 0, 0.5 or 4
      g/L. In peripheral blood and kidney marrow, blood cell counts returned to normal.
      The severity of liver and kidney lesions lessened after 7 days recovery in non
      oiled water, but splenic congestion remained in all gar.

PMID- 25956544
TI  - The influence of fire-coral colony size and agonistic behaviour of territorial
      damselfish on associated coral reef fish communities.
AB  - Branching hydrocorals from the genus Millepora play an important ecological role
      in South Atlantic reefs, where branching scleractinian corals are absent.
      Previous studies have shown a high proportion of reef fish species using
      branching fire-coral colonies as shelter, breeding, and feeding sites. However,
      the effects of Millepora spp. colony size and how the agonistic behaviour of a
      competitive damselfish affect the associated reef fish community are still
      unknown. The present study examined how fire-coral colony volume and the presence
      of a highly territorial and aggressive damselfish (Brazilian endemic Stegastes
      fuscus) affects the reef fish community associated with the fire-coral Millepora
      alcicornis. M. alcicornis colonies were surveyed from September 2012 to April
      2013 at Tamandare Reefs off Northeast Brazil. Our results show that the abundance
      and richness of coral associated fish was positively correlated with M.
      alcicornis coral colony volume. Additionally, behaviour of S. fuscus, the most
      abundant reef fish species found associated with fire-coral colonies (almost 57%
      of the fish community), was also influenced by fire-coral colony volume. There
      was a clear trend of increased agonistic behaviour and feeding on coral polyps as
      colony volume increased. This trend was reversed for the non-occupational
      swimming category, which decreased as M. alcicornis colony volume increased.
      Behavioural ontogenetic changes were also detected for S. fuscus individuals.
      Juveniles mainly showed two distinct behaviours: sheltered on coral branches and
      feeding on coral polyps. In contrast, adults presented greater equitability among
      the behavioural categories, mostly non-occupational swimming around coral
      colonies and agonistic behaviour. Lastly, S. fuscus individuals actively defended
      fire-coral colonies from intruders. A large number of agonistic interactions
      occurred against potential food competitors, which were mainly roving herbivores,
      omnivores, and sessile invertebrate feeders. To our knowledge, the present study
      provides the first evidence that through habitat competition, the presence of S.
      fuscus may affect reef fish communities associated with M. alcicornis coral
      colonies. Our findings also indicate that S. fuscus uses M. alcicornis coral
      colonies as part of their territory for shelter and foraging. In conclusion, M.
      alcicornis fire-coral colonies are extremely important habitats for reef fishes
      and the size and presence of a territorial damselfish are relevant variables for
      associated reef fish community.

PMID- 25956545
TI  - Effect of different dental articulating papers on SEMG activity during maximum
      clenching.
AB  - This study evaluated the influence of two different occlusal indicators
      (articulating papers of 40MUm and 200MUm) on muscular activity of the temporalis
      anterior (TA) and superficial masseter (MS) during maximum voluntary clenches
      (MVC), using surface electromyography (SEMG). It was hypothesized that an
      articulating paper positioned between dental arches during MVC elicits a
      different muscular activity compared with the occlusion on natural dentition
      (without the occlusal indicator). 30 healthy adult subjects with a complete,
      natural dentition were recruited; SEMG activity was recorded in the following
      experimental conditions: MVC with cotton rolls for standardization purposes; MVC
      on natural dentition; MVC onto the 40MUm or 200MUm paper indicator positioned on
      right or left side of the dental arch. Percentage Overlapping Coefficient (POC;
      separate values obtained for TA and MS), antero-posterior coefficient (APC) and
      total muscle activities (IMP) were the analyzed SEMG parameters. The use of an
      occlusal indicator statistically changed POC_TA, POC_MS and IMP median values
      (p<0.05). Both 40MUm and 200MUm occlusal papers did not significantly affect APC
      values (P=0.86). A pronounced asymmetric muscular activity has been recorded with
      the introduction of an interocclusal media. All indices of muscular activity did
      not differ between sexes (Kruskal Wallis test, P>0.05). In conclusion, the
      examined articulating papers affected two specific SEMG parameters (POC and IMP);
      the recorded muscular activity with the occlusal indicator varied regardless left
      or right side positioning, and independently from tested paper thicknesses. 

PMID- 25956546
TI  - Muscle shear elastic modulus is linearly related to muscle torque over the entire
      range of isometric contraction intensity.
AB  - Muscle shear elastic modulus is linearly related to muscle torque during low
      level contractions (<60% of Maximal Voluntary Contraction, MVC). This measurement
      can therefore be used to estimate changes in individual muscle force. However, it
      is not known if this relationship remains valid for higher intensities. The aim
      of this study was to determine: (i) the relationship between muscle shear elastic
      modulus and muscle torque over the entire range of isometric contraction and (ii)
      the influence of the size of the region of interest (ROI) used to average the
      shear modulus value. Ten healthy males performed two incremental isometric little
      finger abductions. The joint torque produced by Abductor Digiti Minimi was
      considered as an index of muscle torque and elastic modulus. A high coefficient
      of determination (R(2)) (range: 0.86-0.98) indicated that the relationship
      between elastic modulus and torque can be accurately modeled by a linear
      regression over the entire range (0% to 100% of MVC). The changes in shear
      elastic modulus as a function of torque were highly repeatable. Lower R(2) values
      (0.89+/-0.13 for 1/16 of ROI) and significantly increased absolute errors were
      observed when the shear elastic modulus was averaged over smaller ROI, half, 1/4
      and 1/16 of the full ROI) than the full ROI (mean size: 1.18+/-0.24cm(2)). It
      suggests that the ROI should be as large as possible for accurate measurement of
      muscle shear modulus. 

PMID- 25956547
TI  - Residual force enhancement in humans: Current evidence and unresolved issues.
AB  - Following an active lengthening contraction while maintaining activation
      constant, isometric force is elevated above that of a purely isometric
      contraction at the same final muscle length. This fundamental property of
      skeletal muscle is referred to as residual force enhancement. While the
      contractile mechanisms of residual force enhancement are still highly-debated,
      from an applied perspective this review focuses on the potential physiological
      relevance of residual force enhancement in human movement. Moreover, this work
      aims to highlight commonalities as well as discrepancies to well accepted history
      dependent properties analyzed in muscle preparations. This will help to identify
      aspects of residual force enhancement in vivo requiring further research. In the
      first part of this review a phenomenological description of residual force
      enhancement in vivo as observed in numerous experiments will be presented. These
      include voluntary as well as electrically stimulated contractions of isolated
      small muscles up to coordinated multi-joint contractions of humans at maximal and
      submaximal activation level. Secondly, we show that residual force enhancement
      during voluntary contractions is not necessarily purely mechanical in nature, but
      also influenced by neural control in terms of more efficient activation,
      increased excitability, saving of metabolic energy, and maintains muscle function
      in acutely and chronically altered neuromuscular states like fatigue, muscle
      damage and aging. Finally, this review focuses on implications of residual force
      enhancement for human movement and future directions for research on residual
      force enhancement in the context of human motor control. 

PMID- 25956548
TI  - Neuromuscular strategies contributing to faster multidirectional agility
      performance.
AB  - The aim of this study was to first determine differences in neuromuscular
      strategy between a faster and slower agility performance, and second compare
      differences in muscle activation strategy employed when performing two closely
      executed agility movements. Participants recruited from an elite female
      basketball team completed an ultrasound to determine quadriceps muscle-cross
      sectional area; reactive isometric mid-thigh pull to determine the rate of muscle
      activation, rate of force development, pre-motor time and motor time; and
      multidirectional agility tests completing two directional changes in response to
      a visual stimulus. Peak and average relative muscle activation of the rectus
      femoris, vastus medialis, vastus lateralis, biceps femoris, semitendinosus and
      gastrocnemius were measured 100ms prior to heel strike (pre-heel strike) and
      across stance phase for both directional changes. Faster agility performance was
      characterized by greater pre-heel strike muscle activity and greater anterior
      muscle activation during stance phase resulting in greater hip and knee extension
      increasing propulsive impulse. Differences between directional changes appear to
      result from processing speed, where a greater delay in refractory times during
      the second directional change resulted in greater anterior muscle activation,
      decelerating the body while movement direction was determined. 

PMID- 25956549
TI  - Validation of the Lymphoedema Quality-of-Life Questionnaire (LYMQOL) in Dutch
      Patients Diagnosed with Lymphoedema of the Lower Limbs.
AB  - BACKGROUND: The Lymphoedema Quality-of-Life Questionnaire is a validated disease
      specific instrument to measure the impact of lymphoedema on patients' lives. In
      this study, we tested its psychometric properties and validated the use of the
      questionnaire in its Dutch translation. METHODS: We obtained the answers to a
      standardised questionnaire, including Lymphoedema Quality-of-Life Questionnaire
      and Short-Form (36) Health Survey, twice at an interval of 2 weeks in 60 patients
      with lower limb lymphoedema. Feasibility was tested on the basis of missing
      responses and response distribution. Structure was studied using factor analysis.
      The reliability of the Lymphoedema Quality-of-Life Questionnaire was assessed
      using Crohnbach's alpha and test-retest reliability. Construct validity was
      tested by correlating Lymphoedema Quality-of-Life Questionnaire scores with the
      Short-Form (36) Health Survey scores. RESULTS: The response rate was 88.2%. One
      of the 22 items missed >10% of responses; another showed a borderline ceiling
      effect. Internal consistency was good and test-retest reliability was excellent.
      The Lymphoedema Quality-of-Life Questionnaire correlated well with the physical
      component of the Short-Form (36) Health Survey and moderately with the mental
      component, suggesting that its construct validity was good. CONCLUSION: The Dutch
      Lymphoedema Quality-of-Life Questionnaire can be used for health-related quality
      of-life research in lower limb lymphoedema patients.

PMID- 25956550
TI  - Confluence of the right internal iliac vein into a compressed left common iliac
      vein.
AB  - The authors describe the abnormal confluence of the right internal iliac vein
      into a left common iliac vein compressed by the overlying right common iliac
      artery. The prevalence of this combination of abnormalities, evaluated in
      cadavers and in living subjects by CT, was 0.9%. The possible obstacle to venous
      pelvic return by these anomalies is pointed out. 

PMID- 25956551
TI  - Type 2 myocardial infarction: A descriptive analysis and comparison with type 1
      myocardial infarction.
AB  - BACKGROUND: While 'plaque rupture' is the paradigm of type 1 myocardial
      infarction (T1MI), T2MI is myocardial necrosis secondary to oxygen supply-demand
      mismatch. Being a heterogeneous and rather newly defined group, data are lacking
      about T2MI. METHODS: A retrospective review of medical records of patients
      diagnosed with T2MI in the Rabin Cardiology Center, Israel between the years 2007
      and 2012 was performed. Following a descriptive analysis, we used multivariate
      time dependent models to estimate the association of T2MI with the risk for 30
      day, 1-year, and 5-year all-cause-mortality and major adverse cardiovascular
      events (MACE), and compared it to a T1MI group matched for age, gender and
      electrocardiographic changes. RESULTS: The study included 107 T2MI (and 107 T1MI)
      patients. Sepsis, anemia, and atrial fibrillation were the most common
      etiologies. Triple anti-thrombotic therapy was given to 22% of T2MI patients (vs.
      82% of T1MI patients, p<0.001). Twenty-five percent were managed using urgent
      percutaneous coronary intervention. Angiography unmasked acute plaque rupture in
      29% of T2MI patients group. Compared to T1MI, T2MI was associated with higher all
      cause-mortality rate: adjusted-hazard-ratio 7.14 (1.31-38.9) at 30 days, 3.42
      (1.51-7.75) at 1 year, and 2.08 (1.14-3.81) at 5 years follow-up. MACE risk was
      consistent between T2 and T1MI patients. CONCLUSIONS: The most common T2MI
      triggers are sepsis, anemia, and atrial fibrillation. Compared to a T1MI
      population, T2MI is associated with higher short- and long-term mortality rates
      but equal cardiovascular mortality and MACE risk. As many as 30% may harbor
      plaque rupture and in fact have T1MI.

PMID- 25956552
TI  - Simultaneous fat and bone assessment in hospitalized heart failure patients using
      non-contrast-enhanced computed tomography.
AB  - BACKGROUND: Heart failure (HF) is associated with adverse metabolic influences
      and provokes fat loss as well as bone and muscle loss at the terminal stages.
      Pericardial fat is an ectopic fat depot that can potentially affect the
      myocardium, but the role of pericardial fat in HF is unclear. We sought to
      characterize pericardial fat in HF, particularly in association with bone tissue
      using cardiac computed tomography (CT). METHODS: In 61 consecutive hospitalized
      HF patients with left ventricular ejection fraction <=50%, pericardial fat volume
      (PFV), CT density in the thoracic vertebrae, and ectopic calcification in the
      aortic valve were assessed simultaneously using electrocardiogram-gated non
      contrast-enhanced CT. RESULTS: The mean PFV was 93.5+/-50.6cm(3), which might
      reflect the total body fat measured with dual energy X-ray absorptiometry
      (Pearson's r=0.48, p=0.01). The PFV index, defined as the PFV/body surface area,
      was significantly higher among older patients (>65 years; 63.5+/-30.6cm(3)/m(2)
      vs. 42.7+/-17.1cm(3)/m(2), p<0.01) and among patients with atrial fibrillation
      (AF; 70.9+/-36.4cm(3)/m(2) vs. 48.8+/-21.2cm(3)/m(2), p<0.01) and hypertension
      (60.7+/-29.3cm(3)/m(2) vs. 41.5+/-18.2cm(3)/m(2), p<0.01) compared to patients
      without these conditions. The PFV indices were comparable between the patients
      with and without ischemic etiology, diabetes, and renal dysfunction. Patients
      with increased PFV indices (above the median) exhibited lower CT density in the
      thoracic vertebrae (134+/-41 Hounsfield units vs. 161+/-57 Hounsfield units,
      p=0.04), and were more likely to have aortic valve calcification (48% vs. 18%,
      p=0.02) and N-telopeptide (bone resorption marker; 20.7+/-5.2nmolBCE/mmolCr vs.
      25.5+/-5.9nmolBCE/mmolCr, p=0.03) levels than those without increased PFV
      indices. CONCLUSIONS: We simultaneously assessed the pericardial fat and bone
      tissue of HF patients with CT and successfully characterized AF, hypertension,
      and advanced age as factors that are associated with increased PFV. PFV was
      correlated with bone tissues and alterations in bone turnover.

PMID- 25956554
TI  - Informed choice and the nanny state: learning from the tobacco industry.
AB  - OBJECTIVES: To examine the 'nanny state' arguments used by tobacco companies,
      explore the cognitive biases that impede smokers' ability to make fully informed
      choices, and analyse the implications for those working to limit the harmful
      effects of other risk products. STUDY DESIGN: A critical analysis of the
      practices engaged in by the tobacco industry, the logic on which they relied, and
      the extent to which their work has informed approaches used by other industries.
      RESULTS: The tobacco industry's deliberate strategy of challenging scientific
      evidence undermines smokers' ability to understand the harms smoking poses and
      questions arguments that smoking is an informed choice. Cognitive biases
      predispose smokers to discount risk information, particularly when this evidence
      is disputed and framed as uncertain. Only state intervention has held the tobacco
      industry to account and begun ameliorating the effects of their sustained
      duplicity. Evidence other industries are now adopting similar tactics,
      particularly use of 'nanny state' claims to oppose proportionate interventions,
      is concerning. CONCLUSIONS: Some marketing strategies have deliberately mis
      informed consumers thus directly contributing to many public health problems. Far
      from removing free choice, government policies that restrain commercial
      communications and stimuli are prerequisites necessary to promote free choice.

PMID- 25956553
TI  - Dysregulated cholinergic network as a novel biomarker of poor prognostic in
      patients with head and neck squamous cell carcinoma.
AB  - BACKGROUND: In airways, a proliferative effect is played directly by cholinergic
      agonists through nicotinic and muscarinic receptors activation. How tumors
      respond to aberrantly activated cholinergic signalling is a key question in
      smoking-related cancer. This research was addressed to explore a possible link of
      cholinergic signalling changes with cancer biology. METHODS: Fifty-seven paired
      pieces of head and neck squamous cell carcinoma (HNSCC) and adjacent non
      cancerous tissue (ANCT) were compared for their mRNA levels for ACh-related
      proteins and ACh-hydrolyzing activity. RESULTS: The measurement in ANCT of
      acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities (5.416 +/
      0.501 mU/mg protein and 6.350 +/- 0.599 mU/mg protein, respectively)
      demonstrated that upper respiratory tract is capable of controlling the
      availability of ACh. In HNSCC, AChE and BChE activities dropped to 3.584 +/-
      0.599 mU/mg protein (p = 0.002) and 3.965 +/- 0.423 mU/mg protein (p < 0.001).
      Moreover, tumours with low AChE activity and high BChE activity were associated
      with shorter patient overall survival. ANCT and HNSCC differed in mRNA levels for
      AChE-T, alpha3, alpha5, alpha9 and beta2 for nAChR subunits. Tobacco exposure had
      a great impact on the expression of both AChE-H and AChE-T mRNAs. Unaffected and
      cancerous pieces contained principal AChE dimers and BChE tetramers. The lack of
      nerve-born PRiMA-linked AChE agreed with pathological findings on nerve terminal
      remodelling and loss in HNSCC. CONCLUSIONS: Our results suggest that the low AChE
      activity in HNSCC can be used to predict survival in patients with head and neck
      cancer. So, the ChE activity level can be used as a reliable prognostic marker.

PMID- 25956556
TI  - Can healthy people benefit from health apps?

PMID- 25956555
TI  - Preventing avoidable sight loss: a public health priority.

PMID- 25956557
TI  - Distress tolerance in OCD and anxiety disorders, and its relationship with
      anxiety sensitivity and intolerance of uncertainty.
AB  - There is a growing interest in the role of distress tolerance (i.e., the capacity
      to withstand negative emotions) in the onset and maintenance of anxiety. However,
      both empirical and theoretical knowledge regarding the role of distress tolerance
      in the anxiety disorders is relatively under examined. Accumulating evidence
      supports the relationship between difficulties tolerating distress and anxiety in
      nonclinical populations; however, very few studies have investigated distress
      tolerance in participants with diagnosed anxiety disorders. Individuals with
      social anxiety disorder (SAD), generalized anxiety disorder (GAD), panic disorder
      with and without agoraphobia (PD/A) and obsessive-compulsive disorder (OCD)
      completed measures of distress tolerance (DT), conceptually related measures
      (i.e., anxiety sensitivity (AS), intolerance of uncertainty (IU)), and anxiety
      symptom severity. Results showed that DT was negatively associated with AS and
      IU. DT was correlated with GAD, SAD and OCD symptoms, but not PD/A symptoms, in
      individuals with those respective anxiety disorders. DT was no longer a
      significant predictor of OCD or anxiety disorder symptom severity when AS and IU
      were also taken into account. There were no between group differences on DT
      across OCD and the anxiety disorder groups. Implications for the role of distress
      tolerance in anxiety pathology are discussed. 

PMID- 25956558
TI  - The correlates of obsessive-compulsive, schizotypal, and borderline personality
      disorders in obsessive-compulsive disorder.
AB  - We assessed correlates of obsessive-compulsive (OCPD), schizotypal (SPD) and
      borderline (BPD) personality disorders in 110 obsessive-compulsive disorder (OCD)
      patients. We found OCD patients with OCPD (20.9%) to exhibit higher rates of
      hoarding and bipolar disorders, increased severity of hoarding and symmetry,
      lower prevalence of unacceptable thoughts involving sex and religion and less non
      planning impulsivity. Conversely, OCD patients with SPD (13.6%) displayed more
      frequently bipolar disorder, increased severity of depression and OCD
      neutralization, greater prevalence of "low-order" behaviors (i.e., touching),
      lower low-planning impulsivity and greater "behavioral" compulsivity. Finally, in
      exploratory analyses, OCD patients with BPD (21.8%) exhibited lower education,
      higher rates of several comorbid psychiatric disorders, greater frequency of
      compulsions involving interpersonal domains (e.g. reassurance seeking), increased
      severity of depression, anxiety and OCD dimensions other than symmetry and
      hoarding, more motor and non-planning impulsivity, and greater "cognitive"
      compulsivity. These findings highlight the importance of assessing personality
      disorders in OCD samples. 

PMID- 25956559
TI  - [Effect of an educational intervention on the attitudes of the nurses of primary
      care on depression].
AB  - OBJECTIVE: To describe nurse attitudes toward depression, using a standardized
      questionnaire and to evaluate how a training workshop can modify or influence
      these attitudes. METHODS: A prospective study based on the application of the
      Depression Attitude Questionnaire, before and six months after, participating in
      a training day on the nursing role in the management of depression in Primary
      Care. The sample consisted of 40 Primary Care nurses from 10 health centers in
      the province of Tarragona. RESULTS: Nurses are in a neutral position when
      considering the management of depressed patients as a difficult task, or to feel
      comfortable in this task, but there is a high degree of acceptance of the claim
      that the time spent caring for depressed patients is rewarding. In general, there
      was little significant difference in the mean scores for the different items of
      the Depression Attitude Questionnaire, before and six months, after the training
      intervention. CONCLUSIONS: The attitude towards the management of depression in
      Primary Care and to the role that nurses can play in this task is generally
      favorable. Fruitful training and organizational initiatives can be established in
      order to define and structure the nursing role in the management of depression in
      Primary Care.

PMID- 25956560
TI  - Exploring 1,4-dihydroxyanthraquinone as long-range emissive ratiometric
      fluorescent probe for signaling Zn(2+)/PO4(3-): Ensemble utilization for live
      cell imaging.
AB  - Fluorescent 1,4-dihydroxyanthraquinone 1 was found to demonstrate its ratiometric
      signaling property upon interaction with divalent zinc (Zn(2+)). While the probe
      itself exhibited fluorescence emission in the yellow region (lambdaem=544 nm and
      567 nm), binding with Zn(2+) induced strong emission in the orange region
      (lambdaem=600 nm) which was mainly due to a combination of CHEF and ICT
      mechanism. The probe was found to be highly sensitive toward the detection of
      zinc and the limit of detection (LOD) was calculated to be 9*10(-7) M. The
      possibility of using this probe for real-time analysis was strongly supported by
      the striking stability of fluorescence signal for more than five days with
      similar fluorescence intensity as observed during instant signaling. The present
      probe works within physiological pH range and is devoid of any interference
      caused by the same group elements such as Cd(2+)/Hg(2+). The probe possesses
      excellent excitation/emission wavelength profile and can penetrate cell membrane
      to image low concentration of zing inside living system. The in situ formed zinc
      probe ensemble was further explored as ratiometric sensing platform for detecting
      another bio-relevant analyte phosphate anion through a zinc-displacement
      approach.

PMID- 25956561
TI  - The effects of heavy metals and their interactions with polycyclic aromatic
      hydrocarbons on the oxidative stress among coke-oven workers.
AB  - Heavy metals and polycyclic aromatic hydrocarbons (PAHs) are predominate toxic
      constituents of particulate air pollution that may be related to the increased
      risk of cardiopulmonary events. We aim to investigate the effects of the toxic
      heavy metals (arsenic, As; cadmium, Cd; chromium, Cr; nickel, Ni; and lead, Pb),
      and their interactions with PAHs on oxidative stress among coke-oven workers. A
      total of 1333 male workers were recruited in this study. We determined their
      urinary levels of As, Cd, Cr, Ni, Pb, twelve PAH metabolites, 8
      hydroxydeoxyguanosine (8-OHdG), and 8-iso-prostaglandin-F2alpha (8-iso
      PGF2alpha). Multivariate linear regression models were used to analyze the
      effects of these metals and their interactions with PAHs on 8-OHdG and 8-iso
      PGF2alpha levels. It was found that only urinary As and Ni showed marginal or
      significant positive linear dose-dependent effects on 8-OHdG in this study
      population, especially among smokers (beta=0.103, P=0.073 and beta=0.110,
      P=0.002, respectively). After stratifying all participants by the quartiles of
      SigmaOH-PAH, all five metals showed linear association with 8-OHdG in the highest
      quartile subgroup (Q4) of SigmaOH-PAHs. However, these five urinary metals showed
      significantly consistent linear associations with 8-iso-PGF2alpha in all subjects
      and each stratum. Urinary SigmaOH-PAHs can significant modify the effects of
      heavy metals on oxidative stress, while co-exposure to both high levels of
      SigmaOH-PAHs and heavy metals render the workers with highest 8-OHdG and 8-iso
      PGF2alpha (all P(interaction)<=0.005). This study showed evidence on the
      interaction effects of heavy metals and PAHs on increasing the oxidative stress,
      and these results warrant further investigation in more longitudinal studies.

PMID- 25956562
TI  - [Anti-VEGF therapy in the treatment of anterior segment neovascularization
      secondary to central retinal vein occlusion].
AB  - PURPOSE: To evaluate the benefit of anti-VEGF in the treatment of anterior
      segment neovascularization (ASNV), a severe complication of ischemic central
      retinal vein occlusion (CRVO). PATIENTS AND METHODS: This is a retrospective case
      series of consecutive patients with ASNV secondary to CRVO treated with anti
      VEGF. Ophthalmic parameters were recorded for each visit: measurement of best
      visual acuity (VA), intraocular pressure (IOP), iris examination, gonioscopy and
      fundus examination, and as necessary, fluorescein angiography and optical
      coherence tomography. Minimum follow-up was 6 months. RESULTS: Nineteen patients
      (19 eyes) received intravitreal injections of anti-VEGF in association with
      panretinal photocoagulation (PRP). In patients who had uncomplicated rubeosis
      iridis without elevated IOP (n=6), after a mean of 3 injections, VA was stable in
      4 patients and improved by two lines in 2 patients. In patients with early
      neovascular glaucoma (NVG) (n=13), IOP reduction was observed in all eyes within
      1 week after injection but increased secondarily after an average of 45 days,
      although the rubeosis had definitively disappeared, which suggested that the
      change in IOP was independent of ASNV. After a mean of 6 injections in
      combination with filtering or cyclodestructive surgery, IOP finally stabilized,
      but VA decreased in all patients. Three patients (50%) with stage III ASNV
      progressed to stage IV ASNV in spite of anti-VEGF treatment. CONCLUSION: In all
      eyes, anti-VEGF treatment stopped neovascularization and helped to control IOP.
      However, vision was preserved only in the eyes with uncomplicated rubeosis at the
      time of diagnosis. Since only 32% of eyes were diagnosed at this stage, the
      authors suggest the prevention of ASNV by careful screening and follow-up of
      patients at risk, and the performance of PRP in CRVO with extensive retinal non
      perfusion prior to the onset of rubeosis.

PMID- 25956563
TI  - Mannose-binding lectin in chronic hepatitis C in children.
AB  - OBJECTIVE: To investigate effect of mannose-binding lectin (MBL) genetic
      polymorphisms and phenotype in chronic hepatitis C and its impact on response to
      antiviral therapy in children. METHODS: Fifty four children with chronic
      hepatitis C, aged 2.5-18 years were enrolled. Forty-five children were treated
      with interferon-alpha (IFN-alpha) alone (n = 2) or IFN-alpha and ribavirin (n =
      43). Twenty-one children who responded to antiviral therapy were defined as
      sustained responders to therapy (IFN-SR). Before therapy, MBL genotypes and serum
      MBL levels (by ELISA) were determined. MBL genotype distribution and levels were
      correlated to disease characteristics and response to therapy. RESULTS: Children
      with chronic hepatitis C who did not respond to antiviral therapy (IFN-NR)
      presented more frequently MBL2 polymorphisms, although this did not reach
      significance (p = 0.08). MBL levels were significantly lower in children
      classified as IFN-NR when compared to children defined as IFN-SR (1.623 ng/ml vs.
      3.699 ng/ml), (p = 0.04). Serum activity levels of ALT and AST were higher in
      children with A/O MBL genotype when compared to group with A/A genotype (p <
      0.05). CONCLUSIONS: Our findings suggest negative effect of MBL deficiency
      (defined by genotype and phenotype) on progression of chronic hepatitis C in
      children and response to antiviral therapy.

PMID- 25956566
TI  - Detection of K-complexes and sleep spindles (DETOKS) using sparse optimization.
AB  - BACKGROUND: This paper addresses the problem of detecting sleep spindles and K
      complexes in human sleep EEG. Sleep spindles and K-complexes aid in classifying
      stage 2 NREM human sleep. NEW METHOD: We propose a non-linear model for the EEG,
      consisting of a transient, low-frequency, and an oscillatory component. The
      transient component captures the non-oscillatory transients in the EEG. The
      oscillatory component admits a sparse time-frequency representation. Using a
      convex objective function, this paper presents a fast non-linear optimization
      algorithm to estimate the components in the proposed signal model. The low
      frequency and oscillatory components are used to detect K-complexes and sleep
      spindles respectively. RESULTS AND COMPARISON WITH OTHER METHODS: The performance
      of the proposed method is evaluated using an online EEG database. The F1 scores
      for the spindle detection averaged 0.70 +/- 0.03 and the F1 scores for the K
      complex detection averaged 0.57 +/- 0.02. The Matthews Correlation Coefficient
      and Cohen's Kappa values were in a range similar to the F1 scores for both the
      sleep spindle and K-complex detection. The F1 scores for the proposed method are
      higher than existing detection algorithms. CONCLUSIONS: Comparable run-times and
      better detection results than traditional detection algorithms suggests that the
      proposed method is promising for the practical detection of sleep spindles and K
      complexes.

PMID- 25956565
TI  - Biocompatibility assessment of spark plasma-sintered alumina-titanium cermets.
AB  - Alumina-titanium materials (cermets) of enhanced mechanical properties have been
      lately developed. In this work, physical properties such as electrical
      conductivity and the crystalline phases in the bulk material are evaluated. As
      these new cermets manufactured by spark plasma sintering may have potential
      application for hard tissue replacements, their biocompatibility needs to be
      evaluated. Thus, this research aims to study the cytocompatibility of a novel
      alumina-titanium (25 vol. % Ti) cermet compared to its pure counterpart, the
      spark plasma sintered alumina. The influence of the particular surface properties
      (chemical composition, roughness and wettability) on the pre-osteoblastic cell
      response is also analyzed. The material electrical resistance revealed that this
      cermet may be machined to any shape by electroerosion. The investigated specimens
      had a slightly undulated topography, with a roughness pattern that had similar
      morphology in all orientations (isotropic roughness) and a sub-micrometric
      average roughness. Differences in skewness that implied valley-like structures in
      the cermet and predominance of peaks in alumina were found. The cermet presented
      a higher surface hydrophilicity than alumina. Any cytotoxicity risk associated
      with the new materials or with the innovative manufacturing methodology was
      rejected. Proliferation and early-differentiation stages of osteoblasts were
      statistically improved on the composite. Thus, our results suggest that this new
      multifunctional cermet could improve current alumina-based biomedical devices for
      applications such as hip joint replacements. 

PMID- 25956567
TI  - P2X3 receptors and sensitization of autonomic reflexes.
AB  - A great deal of basic and applied physiology and pharmacology in sensory and
      autonomic neuroscience has teased apart mechanisms that drive normal perception
      of mechanical, thermal and chemical signals and convey them to CNS, the
      distinction of fiber types and receptors and channels that mediate them, and how
      they may become dysfunctional or maladaptive in disease. Likewise, regulation of
      efferent autonomic traffic to control organ reflexes has been well studied. In
      both afferent and efferent limbs, a wide array of potential therapeutic
      mechanisms has surfaced, some of which have progressed into clinic, if not full
      regrastration. One conversation that has been less well progressed relates to how
      the afferent limb and its sensitization shapes the efferent outputs, and where
      modulation may offer new therapeutic avenues, especially for poorly addressed and
      common signs and symptoms of disease. Therapeutics for CV disease (HF,
      hypertension), respiratory disease (asthma, COPD), urological disease (OAB), GI
      disease (IBS), and inter alia, have largely focused on the efferent control of
      effector cells to modulate movement, contraction and secretion; medicinal needs
      remain with limits to efficacy, AEs and treatment resistance being common. We now
      must turn, in the quest for improved therapeutics, to understand how sensation
      from these organs becomes maladapted and sensitized in disease, and what
      opportunities may arise for improved therapeutics given the abundance of targets,
      many pharmacologically untapped, on the afferent side. One might look at the
      treatment resistant hypertension and the emerging benefit of renal denervation;
      or urinary bladder overactivity / neurogenic bladder and the emergence of
      neuromodulation, capsaicin instillation or botox injections to attenuate
      sensitized reflexes, as examples of merely the start of such progress. This
      review examines this topic more deeply, as applies to four major organ systems
      all sharing a great need from unsatisfied patients. 

PMID- 25956568
TI  - Adiponectin deletion impairs insulin signaling in insulin-sensitive but not
      insulin-resistant 3T3-L1 adipocytes.
AB  - AIMS: Previous reports have demonstrated that the adipocyte-derived peptide
      adiponectin is closely associated with insulin resistance due to its insulin
      sensitizing and anti-inflammatory properties in peripheral tissues; however the
      autocrine effects of adiponectin remain elusive. This study investigated
      regulatory effects of adiponectin on glucose transport and insulin signaling in
      insulin-sensitive or insulin-resistant 3T3-L1 adipocytes. MAIN METHODS: 3T3-L1
      fibroblasts were transfected with non-target or adiponectin (ADN) siRNA and
      differentiated. Chronic treatment with insulin (24h, 100 nM) was employed to
      induce insulin resistance in differentiated adipocytes. Insulin-stimulated
      glucose transport was measured and protein and mRNA levels were assessed by
      Western blot and RT-PCR. KEY FINDINGS: Prolonged incubation with insulin
      significantly reduced insulin-stimulated glucose uptake, suggesting the
      development of insulin resistance and adiponectin mRNA expression. In this
      insulin-resistant condition, adiponectin deletion did not alter insulin
      stimulated glucose uptake. In insulin-sensitive adipocytes, adiponectin ablation
      reduced insulin-stimulated glucose uptake, expression of IRS-1 and GLUT4, and
      GLUT4 translocation to the membrane. Adiponectin knockdown did not affect the
      activation of AKT and p38MAPK (phosphorylation form/total form), but
      significantly decreased the activation of AMPK in insulin-responsive adipocytes.
      SIGNIFICANCE: Adiponectin deficiency suppresses insulin-induced glucose uptake,
      insulin signaling, and the AMPK pathway only in insulin-responsive 3T3-L1
      adipocytes.

PMID- 25956569
TI  - Adjustment method for embedded metrology engine in an EM773 series
      microcontroller.
AB  - This paper presents the problems of implementation and adjustment (calibration)
      of a metrology engine embedded in NXP's EM773 series microcontroller. The
      metrology engine is used in a smart metering application to collect data about
      energy utilization and is controlled with the use of metrology engine adjustment
      (calibration) parameters. The aim of this research is to develop a method which
      would enable the operators to find and verify the optimum parameters which would
      ensure the best possible accuracy. Properly adjusted (calibrated) metrology
      engines can then be used as a base for variety of products used in smart and
      intelligent environments. This paper focuses on the problems encountered in the
      development, partial automatisation, implementation and verification of this
      method. 

PMID- 25956564
TI  - Maturing human pluripotent stem cell-derived cardiomyocytes in human engineered
      cardiac tissues.
AB  - Engineering functional human cardiac tissue that mimics the native adult
      morphological and functional phenotype has been a long held objective. In the
      last 5 years, the field of cardiac tissue engineering has transitioned from
      cardiac tissues derived from various animal species to the production of the
      first generation of human engineered cardiac tissues (hECTs), due to recent
      advances in human stem cell biology. Despite this progress, the hECTs generated
      to date remain immature relative to the native adult myocardium. In this review,
      we focus on the maturation challenge in the context of hECTs, the present state
      of the art, and future perspectives in terms of regenerative medicine, drug
      discovery, preclinical safety testing and pathophysiological studies.

PMID- 25956571
TI  - Repeatability of tear meniscus evaluation using spectral-domain Cirrus(r) HD-OCT
      and time-domain Visante(r) OCT.
AB  - PURPOSE: To investigate the intra-rater, inter-rater and inter-device
      repeatability of a spectral-domain OCT (Cirrus) and a time-domain OCT (Visante)
      for tear meniscus height (TMH) and area (TMA) measurements. METHODS: 20
      participants with no known eye disease were recruited. Both eyes of participants
      were imaged with both OCTs under the similar conditions. The inferior tear
      meniscus was imaged at 6 o'clock position whereas the superior meniscus was
      imaged at 12 o'clock position. Data from the right eyes was analyzed. Two raters
      independently measured TMH and TMA using the OCT images, and one rater repeated
      the measurements. Intra-rater, inter-rater and inter-device repeatability of
      measurements were assessed using Bland-Altman plots and pooled standard
      deviation. RESULTS: For intra-rater repeatability, TMH and TMA measurements were
      more repeatable in Cirrus than Visante (95% limits of agreement (LOA): TMH (MUm),
      -22 to 66 (Cirrus), -125 to 45 (Visante); TMA (MUm(2)), -1632 to 5331 (Cirrus), 
      38,050 to 21,874 (Visante)). For inter-rater agreement, TMH and TMA were also
      more repeatable in Cirrus than Visante (95%LOA: TMH (MUm), -29 to 107 (Cirrus), 
      215 to 252 (Visante); TMA (MUm(2)), -6650 to 9567 (Cirrus), -33,119 to 39,272
      (Visante)). Inter-device agreement was poor (95%LOA: TMH (MUm), -158 to 150; TMA
      (MUm(2)), -32,903 to 14,076). There was no significant difference in inferior TMH
      between Cirrus and Visante (p>0.05). Inferior TMA was significantly lower in
      Cirrus by a mean difference of 10,223MUm(2) (95% confidence interval, 5479,
      14,966) (p=0.0002). CONCLUSION: Spectral-domain OCT is superior to time-domain
      OCT for intra-rater and inter-rater repeatability of TMH and TMA measurements.

PMID- 25956570
TI  - Efficient cellular solid-state NMR of membrane proteins by targeted protein
      labeling.
AB  - Solid-state NMR spectroscopy (ssNMR) has made significant progress towards the
      study of membrane proteins in their native cellular membranes. However, reduced
      spectroscopic sensitivity and high background signal levels can complicate these
      experiments. Here, we describe a method for ssNMR to specifically label a single
      protein by repressing endogenous protein expression with rifampicin. Our results
      demonstrate that treatment of E. coli with rifampicin during induction of
      recombinant membrane protein expression reduces background signals for different
      expression levels and improves sensitivity in cellular membrane samples. Further,
      the method reduces the amount of time and resources needed to produce membrane
      protein samples, enabling new strategies for studying challenging membrane
      proteins by ssNMR. 

PMID- 25956572
TI  - Treatment of Sjogren's syndrome dry eye using 0.03% tacrolimus eye drop:
      Prospective double-blind randomized study.
AB  - OBJECTIVE: To describe the clinical efficacy of the treatment of Sjogren's
      syndrome dry eye using 0.03% tacrolimus eye drop. DESIGN: Prospective double
      blind randomized study. SETTING: Institutional outpatient clinic. PARTICIPANTS:
      Forty-eight eyes of twenty-four patients with dry eye related to Sjogren syndrome
      were enrolled in this study. The patients were randomized in 2 groups: tacrolimus
      (n=14) and vehicle (n=10) group. INTERVENTION: The tacrolimus group received a
      vial containing tacrolimus 0.03% (almond oil as vehicle) and the other group
      received the almond oil vehicle. All patients were instructed to use the eye
      drops every 12h in the lower conjunctival sac. MAIN OUTCOME MEASURES: Schirmer I
      test, break-up-time (BUT), corneal fluorescein and Rose Bengal staining scores
      were evaluated in all patients one day before the treatment (baseline), 7, 14, 28
      and 90 days after treatment with the eye drops. RESULTS: The average fluorescein
      and Rose Bengal scores improved statistically after 7 days of treatment and even
      more after 90 days. The average Schirmer I and BUT values were unchanged after 7,
      14 and 21 days but did show an improvement relative to baseline after 28 days of
      treatment. Schirmer I, BUT, fluorescein and Rose Bengal did not show any
      statistical significance in the vehicle group. CONCLUSION: Topical 0.03%
      tacrolimus eye drop improved tear stability and ocular surface status in cases of
      inflammatory or SS-related dry eye. TRIAL REGISTRATION: ClinicalTrials.gov
      Identifier: NCT01850979.

PMID- 25956573
TI  - Comparison of keratometry and white-to-white measurements obtained by Lenstar
      with those obtained by autokeratometry and corneal topography.
AB  - PURPOSE: To compare anterior eye segment measurements obtained using low optical
      coherence reflectometry (LENSTAR LS900, Haag-Streit), autokeratometry (RC-5000,
      Tomey) and corneal topography (Topolyzer, Wavelight). METHODS: In 46 healthy
      subjects, flat keratometry (Kf), steep keratometry (Ks), mean keratometry (Km)
      and white-to-white (WTW) distance were measured by Lenstar, Tomey RC-5000 and
      Topolyzer. RESULTS: Kf and Km measurements of Lenstar were significantly steeper
      than Tomey RC-5000 (both p<0.001), but the 95% LoA of them were narrow (-0.22 to
      0.46D, -0.16 to 0.36D, respectively). There were no significant differences
      between the Kf and Km measurements of Lenstar and Topolyzer, with a narrow 95%
      LoA. There were no significant differences between the Ks measurements of Lenstar
      and Tomey RC-5000, and Lenstar and Topolyzer. A good agreement was found between
      them with 95% LoA of -0.40 to 0.56D, and -0.56 to 0.64D, respectively. WTW
      measurements with Lenstar were greater than those with Tomey RC-5000 and
      Topolyzer (p=0.042, p<0.01, respectively). A good agreement existed between the
      WTW obtained by Lenstar and Topolyzer, Tomey RC-5000, with 95% LoA ranging from 
      0.13 to 0.74mm and -0.33 to 0.51mm. CONCLUSIONS: Generally good agreement was
      found between the Lenstar and Tomey RC-5000, Topolyzer for K and WTW
      measurements. In clinical practice, K and WTW measurements obtained by Lenstar
      and Tomey RC-5000, Topolyzer can be used interchangeably.

PMID- 25956574
TI  - Minimum Safe Pathologic Excision Margins for Primary Cutaneous Melanomas (1-2 mm
      in Thickness): Analysis of 2131 Patients Treated at a Single Center.
AB  - OBJECTIVE: This study was designed to determine the minimum safe pathologic
      excision margin for primary cutaneous melanomas 1.01-2.00-mm thick (T2) and to
      identify prognostic factors that influence survival in these patients.
      BACKGROUND: Several studies have shown previously that "narrow" clinical excision
      margins (1-2 cm in vivo) are as safe as "wide" excision margins (4-5 cm) for
      management of primary T2 melanomas. However, pathologic margins are likely to be
      a better predictor of recurrence than clinical margins. METHODS:
      Clinicopathologic and follow-up data for 2131 T2 melanoma patients treated at
      Melanoma Institute Australia between January 1992 and May 2012 were analyzed.
      RESULTS: Of the 2131 patients, those who had a pathologic excision margin of <8
      mm (equivalent to 1 cm in vivo) had poorer prognosis in terms of disease-free
      survival compared with the 8-16-mm group (equivalent to 1-2 cm in vivo; P =
      0.044). When comparing 8-mm with 16-mm pathologic margins, no differences were
      observed in any of the survival outcomes. Only the deep margin proved to be an
      independent predictor of local and in-transit recurrence-free survival (P =
      0.003) in all excision margin categories. Pathologic excision margins <8 mm were
      associated with worse regional node recurrence-free survival and distant
      recurrence-free survival compared with margins >=8 mm (P = 0.049 and P = 0.045;
      respectively). However, these results failed to translate into a statistically
      significant difference in melanoma-specific survival. CONCLUSIONS: The results of
      this study suggest that if a peripheral/radial pathologic excision margin for a
      T2 primary cutaneous melanoma is <8 mm consideration should be given to
      performing a wider excision.

PMID- 25956575
TI  - Surgical Outcomes of Lung Cancer in Patients with Combined Pulmonary Fibrosis and
      Emphysema.
AB  - PURPOSE: Lung cancers in patients with combined pulmonary fibrosis and emphysema
      (CPFE) are increasing. Objective of this investigation was to identify which
      clinicopathological features significantly affected surgical outcome of these
      patients. METHODS: Among 4313 patients with primary lung cancers who underwent
      surgery between January 2008 and December 2010 in nine institutions in Japan, 265
      had CPFE. We retrospectively compared 2176 and 157 patients without and with
      CPFE, respectively, and further analyzed 233 patients with CPFE whose detailed
      information was available. CPFE was defined as upper lobe emphysema and lower
      lobe fibrosis. RESULTS: The rates of postoperative morbidity and mortality were
      higher and overall survival was poorer in patients with, than without CPFE. Among
      233 patients with CPFE, the median values of %VC and FEV1.0 % were 98.4 and 71.5
      %, respectively. The histological types comprised 111 squamous cell carcinomas
      and 84 adenocarcinomas. Surgical procedures included 203 standard
      lobectomies/pneumonectomies and 30 lesser resections. Five patients (2 %)
      developed postoperative acute exacerbation of interstitial pneumonia. Six and 15
      patients (3 and 6 %) died within 30- and 90-postoperative-day, respectively.
      Cancer was the cause of death at 90-day in only one patient. The 3-year overall
      survival rate for all patients was 58.4 %. Multivariate analysis showed that male
      sex, advanced age, advanced clinical stage and lower %VC predict a poor
      prognosis. CONCLUSIONS: Patients with lung cancer and CPFE had poor prognoses
      regardless of apparently good pulmonary function and showed quite high
      postoperative mortality rates. A lower %VC that might reflect the severity of
      pulmonary fibrosis was associated with poor prognoses.

PMID- 25956576
TI  - Same-Day Discharge After Laparoscopic Hysterectomy for Endometrial Cancer.
AB  - PURPOSE: The aim of this study was to investigate the relationship between same
      day discharge (SDD) and postoperative complications within 30 days of
      laparoscopic hysterectomy for endometrial cancer and endometrial intraepithelial
      neoplasia (EIN). METHODS: This single-institution retrospective cohort included
      all patients who underwent conventional and robotic-assisted laparoscopic
      hysterectomy for endometrial cancer or EIN in a large teaching hospital between
      2011 and 2013. Temporal trends in frequency of SDD and rates of postoperative
      complications were investigated to assess whether adoption of routine SDD was
      associated with increased postoperative complications. Associations between SDD
      and postoperative complications were also investigated in univariate and
      multivariate models. RESULTS: Overall, 696 patients underwent laparoscopic
      hysterectomy. Of these, 37.1 % had pelvic lymphadenectomy, 3.0 % had para-aortic
      lymphadenectomy, and 9.3 % underwent omentectomy. The rate of SDD increased from
      3.9 to 69.6 % during the study period (p < 0.001), and the frequency of
      postoperative readmission, unscheduled surgery, infection, and composite
      complications within 30 days of hysterectomy did not differ during the study
      period. The composite complication rate did not differ significantly between
      patients who underwent surgery before and after the adoption of routine SDD (rate
      ratio 0.7, 95 % CI 0.4-1.2, p = 0.24). After controlling for demographic,
      intraoperative, and comorbid factors, patients who underwent SDD were not at
      increased risk for postoperative complications. CONCLUSIONS: Adoption of routine
      SDD after laparoscopic surgery for endometrial cancer and EIN did not result in
      increased complication rates within our institution. A larger prospective study
      is required to definitively establish the safety of this approach.

PMID- 25956577
TI  - Impact of Total Lymph Node Count on Staging and Survival After Neoadjuvant
      Chemoradiation Therapy for Rectal Cancer.
AB  - PURPOSE: Current guidelines recommend that a minimum of 12 lymph nodes (LNs) be
      dissected to accurately stage rectal cancer patients. Neoadjuvant chemoradiation
      therapy (CRT) decreases the number of LNs retrieved at surgery. The purpose of
      this study was to assess the impact of the number of LNs dissected on overall
      survival (OS) for localized rectal cancer patients treated with neoadjuvant CRT.
      METHODS: Treatment data were obtained on all patients treated for rectal cancer
      (2000-2013) in the National Oncology Data AllianceTM, a proprietary database of
      merged tumor registries. Eligible patients were treated with neoadjuvant CRT
      followed by surgery and had complete data on number of positive LNs, number of
      LNs examined, and treatment dates (n = 4565). RESULTS: Hazard ratios for OS
      decreased sequentially with increasing number of LNs examined until a maximum
      benefit was achieved with examination of eight LNs. On multivariate analysis,
      age, sex, race, marital status, grade, ypT stage, ypN stage, type of surgery,
      margin status, presence of pathologically confirmed metastasis at surgery, and
      number of LNs examined were significant predictors of OS. CONCLUSIONS:
      Examination of eight or more LNs in rectal cancer patients treated with
      neoadjuvant CRT resulted in accurate staging and assignment into prognostic
      groups with an ensuing improvement in OS by stage. This study suggests that eight
      LNs is the threshold for an adequate lymph node dissection after neoadjuvant CRT.

PMID- 25956578
TI  - Insertion of a Stent in Obstructive Colon Cancer Can Induce a Metastatic Process
      in an Experimental Murine Model.
AB  - BACKGROUND: Colonic self-expanding metallic stents (SEMS) are used in obstructive
      colorectal cancer patients as a bridge to surgery. However, its oncologic safety
      remains uncertain. Therefore, we attempted to clarify this further with an
      experimental study and constructed a mouse model of colonic cancer. METHODS: CT26
      cells were injected in the rectal wall, and to mimic SEMS, a cardiac stent was
      inserted under endoscopy in occlusive (75 % lumen occlusion) tumors. We set up a
      control group (n = 22) and a stent group (n = 16), and the findings were
      compared. We focused on serum lactate dehydrogenase (LDH) concentrations,
      circulating tumor cells, survival time, peritoneal carcinomatosis, liver
      metastases, and bioluminescence. RESULTS: One week after stent insertion, the
      serum LDH concentrations were significantly higher in the stent group (506 +/-
      203 IU/L) compared to the controls (229 +/- 52 IU/L) (P = 0.005). The average
      survival time before sacrifice was significantly lower in the stent group (15.2
      +/- 1 days) compared to the controls (20 +/- 5 days) (P = 0.005). The presence of
      a peritoneal carcinomatosis was more frequently observed in the stent group (75
      %) than in the controls (50 %). Liver metastases were observed in 19 % of the
      stent group compared to the controls (4.5 %) (P = 0.29). After multivariate
      analysis, the stent group was still found to be associated with significantly
      lower survival time (P = 0.002). CONCLUSIONS: These observations led us to
      conclude that in our mouse model, SEMS resulted in an increased metastatic
      process and a shorter survival time. We suggest, therefore, that the utmost
      caution be exercised when opting for a stent as a bridge to surgery.

PMID- 25956579
TI  - Surgical Management of Breast Cancer in 2010-2011 SEER Registries by Hormone and
      HER2 Receptor Status.
AB  - BACKGROUND: Although locoregional recurrence is known to affect overall survival
      for operable breast cancer, the impact of receptor status on locoregional control
      is debated. Currently, hormone receptor (HR) and human epidermal growth factor
      receptor-2 (HER2) status are generally not considered relevant to surgical
      choice. This study examines recent population-level surgical trends with regard
      to receptor status. METHODS: We used the Surveillance, Epidemiology, and End
      Results (SEER) data to identify stage I-III female breast cancers diagnosed from
      2010 to 2011. Patients were categorized by HR and HER2 receptor status.
      Univariate and multivariate logistic regressions were used to assess factors
      associated with undergoing mastectomy and the choice of contralateral
      prophylactic mastectomy (CPM). RESULTS: The overall mastectomy rate for the
      87,504 women diagnosed in 2010-2011 was 43.4 %. On multivariate analysis, the
      odds of receiving mastectomy was greater for HER2-positive disease with either HR
      negative or HR-positive status, than for women with HER2-negative/HR-positive
      disease (odds ratio 1.73 and 1. 31, respectively; all p values <0.001). Age,
      stage, marital status, race, and year of diagnosis also correlated with
      mastectomy. Triple-negative breast cancer (TNBC) was associated with CPM, while
      HER2 status was not. The mastectomy rate, which increased overall from 2006 to
      2010, has continued to increase for stage III disease but has decreased for stage
      I disease. Mastectomy rates overall were lower in 2011 than 2010 (p = 0.012).
      CONCLUSIONS: HER2-positive disease and TNBC were independent predictors of more
      extensive surgery in this large, recent, population-based cohort. Although
      mastectomy rates have continued to increase for stage III disease, mastectomy
      rates overall were lower in 2011 than in previous years.

PMID- 25956580
TI  - A colorectal cancer prediction model using traditional and genetic risk scores in
      Koreans.
AB  - BACKGROUND: Genome-wide association studies have identified numerous single
      nucleotide polymorphisms (SNPs) as associated with colorectal cancer (CRC) risk
      in populations of European descent. However, their utility for predicting risk to
      CRC in Asians remains unknown. A case-cohort study (random sub-cohort N=1,685)
      from the Korean Cancer Prevention Study-II (KCPS-II) (N=145,842) was used. Twenty
      three SNPs identified in previous 47 studies were genotyped on the KCPS-II sub
      cohort members. A genetic risk score (GRS) was calculated by summing the number
      of risk alleles over all SNPs. Prediction models with or without GRS were
      evaluated in terms of the area under the receiver operating characteristic curve
      (AUROC) and the continuous net reclassification index (NRI). RESULTS: Seven of 23
      SNPs showed significant association with CRC and rectal cancer in Koreans, but
      not with colon cancer alone. AUROCs (95% CI) for traditional risk score (TRS)
      alone and TRS plus GRS were 0.73 (0.69-0.78) and 0.74 (0.70-0.78) for CRC, and
      0.71 (0.65-0.77) and 0.74 (0.68-0.79) for rectal cancer, respectively. The NRI
      (95% CI) for a prediction model with GRS compared to the model with TRS alone was
      0.17 (-0.05-0.37) for CRC and 0.41 (0.10-0.68) for rectal cancer alone.
      CONCLUSION: Our results indicate genetic variants may be useful for predicting
      risk to CRC in the Koreans, especially risk for rectal cancer alone. Moreover,
      this study suggests effective prediction models for colon and rectal cancer
      should be developed separately.

PMID- 25956581
TI  - Reduced middle cingulate gyrus volume in late-onset schizophrenia in a Chinese
      Han population: a voxel-based structural MRI study.

PMID- 25956582
TI  - The amount of C1q-adiponectin complex is higher in the serum and the complex
      localizes to perivascular areas of fat tissues and the intimal-medial layer of
      blood vessels of coronary artery disease patients.
AB  - BACKGROUND: The complement component C1q triggers activation of the classical
      immune pathway and can bind to adiponectin (APN). Recently, some studies have
      been reported that serum C1q-APN/total APN ratio correlates with atherosclerosis
      and coronary artery disease (CAD). We assessed the relationships between C1q
      related variables and the severity of CAD, and investigated the localization of
      the C1q-APN complex. METHODS: The sample included 153 subjects comprising healthy
      controls and patients with subclinical or overt CAD. We measured the serum
      concentrations of C1q, total APN, and high-molecular weight (HMW)-APN, and the
      amount of C1q-APN complex. We identified the sites of C1q-APN complex deposition
      in various adipose tissues and blood vessels. RESULTS: Serum concentrations of
      C1q and HMW-APN and the C1q/HMW-APN ratio were independently associated with the
      severity of coronary stenosis. The amount of C1q-APN complex was significantly
      higher in patients with CAD compared with controls. C1q and APN co-localized in
      perivascular areas of subcutaneous, visceral, and pericardial fat tissues, and
      the internal mammary artery of patients with severe CAD. CONCLUSIONS: Serum C1q
      concentration and the C1q/HMW-APN ratio were independent markers of coronary
      artery stenosis. The amount of C1q-APN complex was significantly greater in serum
      from CAD patients. C1q and APN co-localized to perivascular areas in adipose
      tissue and blood vessels. The association between the increased amount of the C1q
      APN complex and CAD should be investigated further.

PMID- 25956583
TI  - Discrete Aspects of FGF21 In Vivo Pharmacology Do Not Require UCP1.
AB  - A primary target of the pleiotropic metabolic hormone FGF21 is adipose tissue,
      where it initiates a gene expression program to enhance energy expenditure, an
      effect presumed to be centered on augmented UCP1 expression and activity. In UCP1
      null (UCP1KO) mice, we show that the effect of FGF21 to increase the metabolic
      rate is abolished. However, in contrast to prior expectations, we found that
      increased UCP1-dependent thermogenesis is only partially required to achieve the
      beneficial effects of FGF21 treatment. In UCP1KO mice, there appears to be an
      underlying reduction in food intake following FGF21 administration, facilitating
      weight loss equal to that observed in wild-type animals. Furthermore, we show
      that UCP1-dependent thermogenesis is not required for FGF21 to improve glycemic
      control or to reduce circulating cholesterol or free fatty acids. These data
      indicate that several important metabolic endpoints of FGF21 are UCP1
      independent; however, the contribution of UCP1-dependent thermogenesis to other
      discrete aspects of FGF21 biology requires further study.

PMID- 25956584
TI  - Continuing Education on Suicide Assessment and Crisis Intervention: What Can We
      Learn About the Needs of Mental Health Professionals in Community Practice?
AB  - This study examined the impact of a 1-day continuing education training for
      mental health professionals on knowledge and confidence around suicide assessment
      and intervention. Data on knowledge, confidence and the utility of information
      were collected through pretests and posttests at 12 trainings at local community
      agencies. Findings indicate that a continuing education workshop can increase
      knowledge and self-confidence. Several participant characteristics were
      associated with knowledge and confidence at pretest; only being trained as a
      mental health professional and previous training remained significant at
      posttest. Participants identified training components which were new and useful.
      Implications for training and education are discussed.

PMID- 25956585
TI  - Diversity and N-acyl-homoserine lactone production by Gammaproteobacteria
      associated with Avicennia marina rhizosphere of South Indian mangroves.
AB  - The diversity of N-acyl-homoserine lactone (AHL)-producing rhizosphere bacterial
      community associated with Avicennia marina in the mangrove ecosystems of South
      India was investigated. Approximately 800 rhizobacteria were isolated from A.
      marina, and they were screened for the production of AHL using two biosensors,
      Chromobacterium violaceum CV026 and Agrobacterium tumefaciens NTL4 (pZLR4). Among
      the total isolates screened, 7% of the rhizobacteria showed positive induction
      for AHL signals. The BOX-PCR profile of 56 positive isolates represented 11
      distinct genotypic groups. Phylogenetic analyses of the 16S rRNA sequences of 16
      representatives showed that the isolates belonged to the class
      Gammaproteobacteria, which represented six different genera: Pseudomonas,
      Aeromonas, Vibrio, Photobacterium, Serratia and Halomonas. The study also
      identified three AHL-producing species, namely, Photobacterium halotolerans MSSRF
      QS48, Vibrio xiamenensis MSSRF QS47 and Pseudomonas sp. MSSRF QS1 that had not
      been reported previously. AHL profiling by TLC detected short chains C4, C6 and
      C8-HSL, and long chains C10 and C12-HSL with both unsubstituted and substituted
      side chains among the 16 representative AHL positives. This is the first report
      concerning the diversity of AHL-producing Gammaproteobacteria from mangrove
      ecosystems exhibiting diverse AHL profiles.

PMID- 25956586
TI  - Neurovascular structures of the mandibular angle and condyle: a comprehensive
      anatomical review.
AB  - BACKGROUND: Various surgical interventions including esthetic surgery, salivary
      gland excision, and open reduction of fracture have been performed in the area
      around the mandibular angle and condyle. This study aimed to comprehensively
      review the anatomy of the neurovascular structures on the angle and condyle with
      recent anatomic and clinical research. METHODS AND RESULTS: We provide detailed
      information about the branching and distributing patterns of the neurovascular
      structures at the mandibular angle and condyle, with reported data of
      measurements and proportions from previous anatomical and clinical research. Our
      report should serve to help practitioners gain a better understanding of the area
      in order or reduce potential complications during local procedures. Reckless
      manipulation during mandibular angle reduction could mutilate arterial branches,
      not only from the facial artery, but also from the external carotid artery. The
      transverse facial artery and superficial temporal artery could be damaged during
      approach and incision in the condylar area. The marginal mandibular branch of the
      facial nerve can be easily damaged during submandibular gland excision or facial
      rejuvenation treatment. The main trunk of the facial nerve and its upper and
      lower distinct divisions have been damaged during parotidectomy, rhytidectomy,
      and open reductions of condylar fractures. CONCLUSION: By revisiting the
      information in the present study, surgeons will be able to more accurately
      prevent procedure-related complications, such as iatrogenic vascular accidents on
      the mandibular angle and condyle, complete and partial facial palsy, gustatory
      sweating (Frey syndrome), and traumatic neuroma after parotidectomy.

PMID- 25956587
TI  - Maternal early-life trauma and affective parenting style: the mediating role of
      HPA-axis function.
AB  - A history of childhood trauma is associated with increased risk for
      psychopathology and interpersonal difficulties in adulthood and, for those who
      have children, impairments in parenting and increased risk of negative outcomes
      in offspring. Physiological and behavioral mechanisms are poorly understood. In
      the current study, maternal history of childhood trauma was hypothesized to
      predict differences in maternal affect and HPA axis functioning. Mother-infant
      dyads (N = 255) were assessed at 6 months postpartum. Mothers were videotaped
      during a 3-min naturalistic interaction, and their behavior was coded for
      positive, neutral, and negative affect. Maternal salivary cortisol was measured
      six times across the study visit, which also included an infant stressor
      paradigm. Results showed that childhood trauma history predicted increased
      neutral affect and decreased mean cortisol in the mothers and that cortisol
      mediated the association between trauma history and maternal affect. Maternal
      depression was not associated with affective measures or cortisol. Results
      suggest that early childhood trauma may disrupt the development of the HPA axis,
      which in turn impairs affective expression during mother-infant interactions in
      postpartum women. Interventions aimed at treating psychiatric illness in
      postpartum women may benefit from specific components to assess and treat trauma
      related symptoms and prevent secondary effects on parenting.

PMID- 25956588
TI  - Transdermal estradiol treatment during breastfeeding: maternal and infant serum
      concentrations.
AB  - We examined estradiol (E2) and estrone (E1) concentrations in breastfeeding
      mother-infant dyads. The mothers had postpartum depression and were participants
      in a randomized clinical trial with three treatments (transdermal E2, sertraline,
      and placebo). Neither infant E1 and E2 concentrations nor infant growth differed
      across the treatments. Transdermal E2 administration of 50 to 200 mcg/day for
      breastfeeding women did not affect infant E1 or E2 concentrations or infant
      growth.

PMID- 25956590
TI  - Union is strength: matrix elasticity and microenvironmental factors codetermine
      stem cell differentiation fate.
AB  - Stem cells are an attractive cellular source for regenerative medicine and tissue
      engineering applications due to their multipotency. Although the elasticity of
      the extracellular matrix (ECM) has been shown to have crucial impacts in
      directing stem cell differentiation, it is not the only contributing factor. Many
      researchers have recently attempted to design microenvironments that mimic the
      stem cell niche with combinations of ECM elasticity and other cues, such as ECM
      physical properties, soluble biochemical factors and cell-cell interactions,
      thereby driving cells towards their preferred lineages. Here, we briefly discuss
      the effect of matrix elasticity on stem cell lineage specification and then
      summarize recent advances in the study of the combined effects of ECM elasticity
      and other cues on the differentiation of stem cells, focusing on two aspects:
      biophysical and biochemical factors. In the future, biomedical scientists will
      continue investigating the union strength of matrix elasticity and
      microenvironmental cues for manipulating stem cell fates. 

PMID- 25956589
TI  - History of childhood sexual abuse and risk of prenatal and postpartum depression
      or depressive symptoms: an epidemiologic review.
AB  - The objective of this review is to summarize the literature (and to the extent
      possible, report the magnitude and direction of the association) concerning
      history of childhood sexual abuse (CSA) and depression or depressive symptoms
      among pregnant and postpartum women. Publications were identified through
      literature searches of seven databases (PubMed, EMBASE, PyscINFO, CINAHL, Web of
      Science, BIOSIS, and Science Direct) using keywords including "child abuse,"
      "depression," "pregnancy," "prenatal," "pregnancy," and "postpartum." The
      literature search yielded seven eligible studies on the prenatal period and
      another seven studies on the postpartum period. All but one prenatal study
      observed statistically significant positive associations of CSA with depression
      or depressive symptoms during pregnancy. Findings on the association of CSA with
      postpartum depression or depressive symptoms were inconsistent; pooled unadjusted
      and adjusted odds ratios were 1.82 (95 % confidence interval (CI) 0.92, 3.60) and
      1.20 (95 % CI 0.81, 1.76). In sum, findings suggest a positive association of
      history of CSA with depression and depressive symptoms in the prenatal period.
      Findings on the postpartum period were inconsistent. Clinical and public health
      implications of evidence from the available literature are discussed, as are
      desirable study design characteristics of future research. 

PMID- 25956591
TI  - Osteogenic priming of mesenchymal stem cells by chondrocyte-conditioned factors
      and mineralized matrix.
AB  - Transient cartilage and a mineralizing microenvironment play pivotal roles in
      mesenchymal cell ossification during bone formation. In order to recreate these
      microenvironmental cues, C3H10T1/2 murine mesenchymal stem cells (MSCs) were
      exposed to chondrocyte-conditioned medium (CM) and seeded onto three-dimensional
      mineralized scaffolds for bone regeneration. Expansion of C3H10T1/2 cells with CM
      resulted in enhanced expression levels of chondrogenic markers such as aggrecan,
      type II collagen, type X collagen, and Sox9, rather than of osteogenic genes.
      Interestingly, CM expansion led to reduced expression levels of osteogenic genes
      such as alkaline phosphatase (ALP), type I collagen, osteocalcin, and Runx2.
      However, CM-expanded C3H10T1/2 cells showed enhanced osteogenic differentiation
      as indicated by increased ALP and Alizarin Red S staining upon osteogenic factor
      exposure. In vivo, CM-expanded C3H10T1/2 mesenchymal cells were seeded onto
      mineralized scaffolds (fabricated with polydopamine and coated with simulated
      body fluids) and implanted into critical-sized calvarial-defect mouse models.
      After 8 weeks of implantation, mouse skulls were collected, and bone tissue
      regeneration was evaluated by micro-computed tumography and Masson's trichrome
      staining. In accordance with the in vitro analysis, CM-expanded C3H10T1/2 cells
      gave enhanced bone mineral deposition. Thus, chondrocyte-conditioned factors and
      a mineralized microenvironment stimulate the bone formation of MSCs. 

PMID- 25956592
TI  - Contribution of demographic and behavioral factors on the changing incidence
      rates of oropharyngeal and oral cavity cancers in northern California.
AB  - BACKGROUND: It is unknown to what extent patient demographics, smoking, and
      alcohol use have contributed to changes in oropharyngeal and oral cavity cancer
      incidence rates. METHODS: We performed a cohort study of Kaiser Permanente health
      plan members, ages 20 to 89, for years 1995-2010 (n = 2.2 million annual
      members). Poisson Regression models estimated calendar trends in cancer rates
      both adjusted for and stratified by age, sex, smoking, and alcohol abuse history.
      RESULTS: We identified 1,383 human papillomavirus (HPV)-related and 1,344 HPV
      unrelated oral cavity and oropharyngeal cancer cases. With adjustment for age and
      sex, HPV-related cancer incidence rates increased 3.8% per year (P < 0.001)
      between 1995 and 2010, whereas rates for HPV-unrelated cancers decreased 2.4% per
      year (P < 0.001). For years 2007 to 2010, with additional adjustment for smoking
      and alcohol abuse, results were nonsignificant, but similar in magnitude. The
      increasing rates for HPV-related cancers were more prominent among nonsmokers
      (+14.5%) compared with smokers (-2.5%; P-interaction = 0.058). The decreased
      rates for HPV-unrelated sites were more prominent among those >= 60 years (
      11.0%) compared with those <60 years (+16.8%; P-interaction = 0.006), among
      smokers (-9.7%) compared with nonsmokers (+8.4%; P-interaction = 0.055), and
      among those with an alcohol abuse history (-20.4%) compared with those without a
      history (+5.8%; P-interaction = 0.009). CONCLUSIONS: The observed increasing HPV
      related cancer rates are most evident among nonsmokers, whereas the decreasing
      HPV-unrelated cancer rates are least evident among younger individuals,
      nonsmokers, and those without an alcohol abuse history. IMPACT: Continued
      vigilance for oropharyngeal and oral cavity cancer is warranted, including among
      those without traditional risk factors such as smoking and alcohol abuse.

PMID- 25956593
TI  - Comparative evaluation of sump drainage by trocar puncture, percutaneous catheter
      drainage versus operative drainage in the treatment of Intra-abdominal abscesses:
      a retrospective controlled study.
AB  - BACKGROUND: Intra-abdominal and pelvic abscesses are common and result from
      various illnesses. Percutaneous drainage applies limitedly to well-localized
      abscesses with appropriate density while surgical drainage usually causes
      significant physiological disturbance. We herein illustrated an innovative choice
      "sump drainage with trocar puncture" for the management of intra-abdominal
      abscesses and compare it with conventional percutaneous and surgical drainage in
      terms of clinical outcomes and prognosis. METHODS: Medical records of a total of
      75 patients with abscesses were retrospectively retrieved and scrutinized. Data
      consisted of demographics, abscesses characteristics and treatment outcomes
      including postoperative complication, duration of hospitalization, postoperative
      recurrence of abscesses, subsequent surgery, ultimate stoma creation and survival
      rate. All enrolled patients were divided into trocar group (n = 30), percutaneous
      group (n = 20) and surgical group (n = 25) according to the therapeutic
      modalities. One-way ANOVA and t-test with Welch's correction were used in
      continuous variables, and Chi-squared test as well as Fisher's exact test for
      categorical variables. The cumulative incidence of subsequent surgery and
      ultimate stoma creation was also indicated by the Kaplan-Meier method and
      compared by log-rank test. RESULTS: The risk of ultimate stoma creation (p =
      0.0069) and duration of postoperative hospitalization (p = 0.0077) were
      significantly decreased in trocar group compared with the surgical group.
      Patients receiving trocar puncture also tended to be less likely to have
      subsequent surgery (p = 0.097). Patients in trocar group displayed a lower rate
      of postoperative complication than the percutaneous (p = 0.0317) and surgical
      groups (p = 0.0175). As for Kaplan-Meier analysis, the cumulative incidence of
      ultimate stoma creation of the patients using sump drainage was also
      significantly different among three groups during follow-up period (p = 0.011).
      CONCLUSION: This novel technique "sump drainage by trocar puncture" could produce
      better clinical outcomes and prognosis than conventional percutaneous drainage
      and surgical intervention. It might become an optimal choice in the management of
      intra-abdominal abscesses in the future.

PMID- 25956594
TI  - Pursuing Pleasures of Productivity: University Students' Use of Prescription
      Stimulants for Enhancement and the Moral Uncertainty of Making Work Fun.
AB  - This article presents ethnographic data on the use of prescription stimulants for
      enhancement purposes by university students in New York City. The study shows
      that students find stimulants a helpful tool in preventing procrastination,
      particularly in relation to feeling disinterested, overloaded, or insecure. Using
      stimulants, students seek pleasure in the study situation, for example, to get
      rid of unpleasant states of mind or intensify an already existing excitement. The
      article illustrates the notion that enhancement strategies do not only concern
      productivity in the quantitative sense of bettering results, performances, and
      opportunities. Students also measure their own success in terms of the
      qualitative experience of working hard. The article further argues that taking an
      ethnographic approach facilitates the study of norms in the making, as students
      experience moral uncertainty-not because they improve study skills and results
      but because they enhance the study experience, making work fun. The article
      thereby seeks to nuance simplistic neoliberal ideas of personhood. 

PMID- 25956595
TI  - A "three delays" model for severe sepsis in resource-limited countries.
AB  - PURPOSE: The developing world carries the greatest burden of sepsis-related
      mortality, but success in managing severe sepsis in resource-limited countries
      (RLCs) remains challenging. A "three delays" model has been developed to describe
      factors influencing perinatal mortality in developing nations. This model has
      been validated across different World Health Organization regions and has
      provided the framework for policymakers to plan targeted interventions. Here, we
      propose a three delays model for severe sepsis in RLCs. MATERIALS AND METHODS: A
      literature review was performed using the PubMed, Google Scholar, and Ovid
      databases. Additional sources were found after review of the reference lists from
      retrieved articles. RESULTS: We propose a three delays model for severe sepsis in
      adults in RLCs. The model highlights limitations in the 3 basic pillars of sepsis
      management: (1) sepsis recognition and diagnosis at the time of triage, (2)
      initial focused resuscitation, and (3) postresuscitation clinical monitoring and
      reassessment. CONCLUSIONS: Characterizing the major barriers to effective
      treatment of severe sepsis in RLCs frames the problem in a language common to
      global health circles, which may stimulate further research, streamline
      treatment, and reduce sepsis-related mortality in the developing world.

PMID- 25956596
TI  - Selective label-free electrochemical impedance measurement of glycated
      haemoglobin on 3-aminophenylboronic acid-modified eggshell membranes.
AB  - We propose a novel alternative approach to long-term glycaemic monitoring using
      eggshell membranes (ESMs) as a new immobilising platform for the selective label
      free electrochemical sensing of glycated haemoglobin (HbA1c), a vital clinical
      index of the glycaemic status in diabetic individuals. Due to the unique features
      of a novel 3-aminophenylboronic acid-modified ESM, selective binding was obtained
      via cis-diol interactions. This newly developed device provides clinical
      applicability as an affinity membrane-based biosensor for the identification of
      HbA1c over a clinically relevant range (2.3 - 14 %) with a detection limit of
      0.19%. The proposed membrane-based biosensor also exhibited good reproducibility.
      When analysing normal and abnormal HbA1c levels, the within-run coefficients of
      variation were 1.68 and 1.83%, respectively. The run-to-run coefficients of
      variation were 1.97 and 2.02%, respectively. These results demonstrated that this
      method achieved the precise and selective measurement of HbA1c. Compared with a
      commercial HbA1c kit, the results demonstrated excellent agreement between the
      techniques (n = 15), demonstrating the clinical applicability of this sensor for
      monitoring glycaemic control. Thus, this low-cost sensing platform using the
      proposed membrane-based biosensor is ideal for point-of-care diagnostics.

PMID- 25956597
TI  - A novel non-invasive sampling method using buccal mucosa cells for determination
      of coenzyme Q10.
AB  - Coenzyme Q10 (CoQ10) is an important cofactor in the mitochondrial respiratory
      chain and a potent endogenous antioxidant. CoQ10 deficiency is often associated
      with numerous diseases, and patients can benefit from CoQ10 supplementation,
      being more effective when diagnosed and treated early. Due to the increased
      interest in CoQ10 deficiency, several methods for CoQ10 analysis from plasmatic,
      muscular, fibroblast, and platelet matrices have been developed. These sampling
      techniques are not only highly invasive but also too traumatic for periodic
      clinical monitoring. In the present work, we describe the development and
      validation of a novel non-invasive sampling method for quantification of CoQ10 in
      buccal mucosa cells (BMCs) by microHPLC. This method is suitable for using in a
      routine laboratory and useful for sampling patients in pediatry. CoQ10
      correlation was demonstrated between BMCs and plasma levels (Spearman r, 0.4540;
      p < 0.001). The proposed method is amenable to be applied in the post treatment
      monitoring, especially in pediatric patients as a non-invasive sample collection.
      More studies are needed to assess whether this determination could be used for
      diagnosis and if this matrix could replace the traditional ones. 

PMID- 25956598
TI  - Gold-nanoparticle extraction and reversed-electrode-polarity stacking mode
      combined to enhance capillary electrophoresis sensitivity for conjugated
      nucleosides and oligonucleotides containing thioether linkers.
AB  - We present a capillary electrophoresis method for determining two different C8
      conjugated deoxyadenosines, and for oligonucleotides containing them, in which a
      psoralen or an acridine molecule is bonded to the base via a short alkyl chain
      containing sulfur ethers at both ends. The sensitivity of the micellar
      electrokinetic chromatography (MEKC) method was increased by using two
      preconcentration techniques, micro solid-phase extraction (MUSPE) followed by
      reversed-electrode-polarity stacking mode (REPSM). Variables that affect the
      efficiency of the extraction in MUSPE and preconcentration by REPSM, including
      the type and volume of extraction nanoparticle, concentration, and injection
      time, were investigated. Under the optimum conditions, enrichment factors
      obtained were in the range 360-400. The limits of detection (LODs) at a signal-to
      noise ratio of 3 ranged from 2 to 5 nmol L(-1). The relative recoveries of
      labelled adenosines from water samples were 95-103%. The proposed method provided
      high enrichment factors and good precision and accuracy with a short analysis
      time. On the basis of the advantages of simplicity, high selectivity, high
      sensitivity, and good reproducibility, the proposed method may have great
      potential for biochemical applications.

PMID- 25956599
TI  - Multivariate modelling on biomass properties of cassava stems based on an
      experimental design.
AB  - Based on a factorial experimental design (three locations * three cultivars *
      five harvest times * four replicates) conducted with the objective of
      investigating variations in fuel characteristics of cassava stem, a multivariate
      data matrix was formed which was composed of 180 samples and 10 biomass
      properties for each sample. The properties included as responses were two
      different calorific values and ash, N, S, Cl, P, K, Ca, and Mg content. Overall
      principal component analysis (PCA) revealed a strong clustering for the growing
      locations, but overlapping clusters for the cultivar types and almost no useful
      information about harvest times. PCA using a partitioned data set (60 * 10) for
      each location revealed a clustering of cultivars. This was confirmed by soft
      independent modelling of class analogy (SIMCA) and partial-least-squares
      discriminant analysis (PLS-DA), and indicated that the locations gave meaningful
      information about the differences in cultivar, whereas harvest time was not found
      to be a differentiating factor. Using the PLS technique, it was revealed that
      ash, K, and Cl content were the most important responses for PLS-DA models.
      Furthermore, using PLS regression of fuel and soil variables it was also revealed
      that fuel K and ash content were correlated with the soil P, Si, Ca, and K
      content, whereas fuel Cl content was correlated with soil pH and content of
      organic carbon, N, S, and Mg in the soil. Thus, the multivariate modelling used
      in this study reveals the possibility of performing rigorous analysis of a
      complex data set when an analysis of variance may not be successful. 

PMID- 25956600
TI  - FRET-based homogeneous immunoassay on a nanoparticle-based photonic crystal.
AB  - The potential of fluorescence resonance energy transfer (FRET) in a photonic
      crystal (PC) nanostructured array to enhance the speed and sensitivity of a
      protein-based immunoassay was tested. Forty-nanometer carboxylated particles
      conjugated with donor-labeled capture antibodies were trapped by electrophoresis
      and used as a FRET energy donor. The PC array was able to enhance fluorescent
      excitation and emission by phase matching. To provide a proof of concept for this
      FRET-based homogeneous assay on a PC chip, an immunoassay was tested with a
      simple immunoglobulin G (IgG)-based reaction. A standard curve was generated by
      testing two different antibody reaction times: 20 min. and 1 min. The results
      were compared directly to those obtained from a FRET assay that used a modern,
      high-sensitivity plate reader with a 96-well plate and a reaction time of 1 h.
      The rabbit-IgG detection limits of the FRET-based homogeneous assay on the PC
      were 0.001 and 0.1 MUg/mL for incubation times of 20 and 1 min, respectively; the
      sensitivities were 10(3) and 10 times better than the 96-well plate reader,
      respectively. Thus, FRET on a PC immunoplatform was shown to be a facile,
      effective, rapid, and sensitive detection technology. 

PMID- 25956601
TI  - Erratum to: Novel polystyrene/antibody nanoparticle-coated capillary for
      immunoaffinity in-tube solid-phase microextraction.

PMID- 25956602
TI  - Gender- and region-dependent changes of redox biomarkers in the brain of
      successfully aging LOU/C rats.
AB  - The LOU/C (LOU) rat is an obesity resistant strain with higher longevity and
      healthspan than common rats. The management of oxidative stress being important
      to successful aging, we characterized this process in the aging LOU rat.
      Male/female LOU rats were euthanized at 4, 20, and 29 months. Macrodissected
      hippocampus, striatum, parietal cortex, cerebellum were assayed for tissue
      concentrations of glutathione (GSH), gamma-glutamyl-cysteine-synthetase (gamma
      GCS), total thiols, protein carbonyls, mRNAs of clusterin and the known
      protective enzymes thioredoxine-1 (TRX-1), glutaredoxine-1 (GLRX-1), superoxide
      dismutase-1 (SOD-1). Brain levels of GSH, gamma-GCS, total thiols remained
      constant with age, except for GSH and gamma-GCS which decreases in females.
      Clusterin, TRX-1, GLRX-1, SOD-1 mRNA levels were maintained or increased in the
      hippocampus with age. Age-dependency of the markers differed between sexes, with
      SOD-1 and TRX-1 decreases out of hippocampus in females. Since antioxidants were
      reported to decrease with age in the brain of Wistar rats, maintenance of GSH
      levels and of protective enzymes mRNA levels in the LOU rat brain could
      contribute to the preservation of cognitive functions in old age. Altogether, the
      successful aging of LOU rats may, at least in part, involve the conservation of
      functional antioxidant mechanisms in the brain, supporting the oxidative stress
      theory of aging. 

PMID- 25956603
TI  - Progressive age-associated activation of JNK associates with conduction
      disruption in the aged atrium.
AB  - Connexin43 (Cx43) is critical for maintaining electrical conduction across atrial
      muscle. During progressive ageing atrial conduction slows associating with
      increasing susceptibility to arrhythmias. Changes in Cx43 protein expression, or
      its phosphorylation status, can instigate changes in the conduction of the
      cardiac action potential. This study investigated whether increased levels of
      activated c-jun N-terminal kinase (JNK) is responsible for the decline of Cx43
      during ageing. Right atria from guinea pigs aged between 1 day and 38 months of
      age were examined. The area of the intercalated disc increased with age
      concurrent with a 75% decline in C43 protein expression. An age-dependent
      increase in activated-JNK correlated with a rise in phosphorylated Cx43, but also
      slowing of action potential conduction velocity across the atria from 0.38+/-0.01
      m/s at 1 month of age to 0.30+/-0.01 m/s at 38 months. The JNK activator
      anisomycin increased activated JNK in myocytes and reduced Cx43 protein
      expression simulating ageing. The JNK inhibitor SP600125, was found to eradicate
      almost all trace of Cx43 protein. We conclude that in vivo activation of JNK
      increases with age leading to the loss of Cx43 protein resulting in impaired
      conduction and contributing to the increasing risk of atrial arrhythmias with
      advancing age.

PMID- 25956604
TI  - Neuronal mechanisms of motor learning and motor memory consolidation in healthy
      old adults.
AB  - It is controversial whether or not old adults are capable of learning new motor
      skills and consolidate the performance gains into motor memory in the offline
      period. The underlying neuronal mechanisms are equally unclear. We determined the
      magnitude of motor learning and motor memory consolidation in healthy old adults
      and examined if specific metrics of neuronal excitability measured by magnetic
      brain stimulation mediate the practice and retention effects. Eleven healthy old
      adults practiced a wrist extension-flexion visuomotor skill for 20 min (MP, 71.3
      years), while a second group only watched the templates without movements
      (attentional control, AC, n = 11, 70.5 years). There was 40 % motor learning in
      MP but none in AC (interaction, p < 0.001) with the skill retained 24 h later in
      MP and a 16 % improvement in AC. Corticospinal excitability at rest and during
      task did not change, but when measured during contraction at 20 % of maximal
      force, it strongly increased in MP and decreased in AC (interaction, p = 0.002).
      Intracortical inhibition at rest and during the task decreased and facilitation
      at rest increased in MP, but these metrics changed in the opposite direction in
      AC. These neuronal changes were especially profound at retention. Healthy old
      adults can learn a new motor skill and consolidate the learned skill into motor
      memory, processes that are most likely mediated by disinhibitory mechanisms.
      These results are relevant for the increasing number of old adults who need to
      learn and relearn movements during motor rehabilitation.

PMID- 25956606
TI  - Cone-beam Computed Tomography Analysis of the Root Canal Morphology of Maxillary
      First and Second Premolars in a Spanish Population.
AB  - INTRODUCTION: We investigated the root canal configuration of maxillary premolars
      in a Spanish population by using cone-beam computed tomography. METHODS: Images
      of 804 maxillary first and second premolars were obtained from 620 patients who
      underwent cone-beam computed tomography scanning during preoperative assessment
      (before implant surgery, orthodontic treatment, dentoalveolar trauma diagnosis,
      or difficult root canal treatment). We determined tooth position, number of
      roots, root canal configuration (Vertucci's classification), number of root
      canals, and number of apical foramina per root and used the chi(2) test to
      analyze the correlation between root number and tooth position. RESULTS: In the
      maxillary first premolar group (n = 430), 46% (n = 198) had 1 root, 51.4% (n =
      221) had 2 roots, and 2.6% (n = 11) had 3 roots. Most exhibited a type IV canal
      configuration (n = 227, 52.8%). Single-rooted teeth had a more variable canal
      configuration, whereas most 2-rooted teeth showed a type IV configuration (n =
      215, 97.3%). In the maxillary second premolar group (n = 374), 82.9% (n = 310)
      had 1 root, 15.5% (n = 58) had 2 roots, and 1.6% (n = 6) had 3 roots. The
      majority of single-rooted second premolars exhibited a type I configuration (n =
      147, 47.2%). Overall, type VIII canals were only observed in 3-rooted teeth. No
      statistical correlation was evident between root number and gender and tooth
      position. CONCLUSIONS: There was a high frequency of 2-rooted and single-rooted
      teeth among maxillary first and second premolars, respectively. The canal
      morphology of single-rooted teeth was highly variable.

PMID- 25956605
TI  - Temporal-controlled Dexamethasone Releasing Chitosan Nanoparticle System Enhances
      Odontogenic Differentiation of Stem Cells from Apical Papilla.
AB  - INTRODUCTION: The spatial and temporal control of stem cell differentiation into
      odontoblast-like cells remains one of the major challenges in regenerative
      endodontic procedures. The current study aims to synthesize and compare the
      effect of dexamethasone (Dex) release from 2 variants of Dex-loaded chitosan
      nanoparticles (CSnp) on the odontogenic differentiation of stem cells from apical
      papilla (SCAP). METHODS: Two variants of Dex-loaded CSnp were synthesized by
      encapsulation (Dex-CSnpI) and adsorption (Dex-CSnpII) methods. The
      physicochemical characterization of Dex-CSnpI and Dex-CSnpII was assessed by
      transmission electron microscopy, Zetasizer, and Fourier transform infrared
      spectroscopy, whereas the Dex release kinetics was assessed by spectrophotometry.
      A previously characterized SCAP cell line was cultured onto CSnp, Dex-CSnpI, or
      Dex-CSnpII. The biomineralization potential was determined by alizarin red
      staining. Alkaline phosphatase, dentin sialophosphoprotein, and dentin matrix
      protein-1 gene expressions were analyzed by real-time reverse-transcription
      polymerase chain reaction. RESULTS: Dex-CSnpI resulted in slower release of Dex
      compared with Dex-CSnpII, but both demonstrated sustained release of Dex for 4
      weeks. Biomineralization of SCAP was significantly higher (P < .05) in presence
      of Dex-CSnpII compared with that in Dex-CSnpI at 3 weeks. Alkaline phosphatase
      gene expression was significantly higher in the presence of Dex-CSnpII compared
      with Dex-CSnpI, with peak expression seen at 2 weeks (P < .05). The expression of
      odontogenic specific marker dentin matrix protein-1 was significantly higher in
      presence of Dex-CSnpII compared with Dex-CSnpI at 3 weeks (P < .05). CONCLUSIONS:
      Collectively, these data suggest that sustained release of Dex results in
      enhanced odontogenic differentiation of SCAP. These findings highlight the
      potential of temporal-controlled delivery of bioactive molecules to direct the
      spatial- and temporal-controlled odontogenic differentiation of dental stem
      cells.

PMID- 25956607
TI  - Dentinogenic Activity of Biodentine in Deep Cavities of Miniature Swine Teeth.
AB  - INTRODUCTION: The aim of the present study was to evaluate comparatively the
      bioactivity potential of a calcium silicate-based material (Biodentine;
      Septodont, Saint-Maur-des-fosses Cedex, France) after the restoration of deep
      dentinal cavities of miniature swine teeth with or without the application of a
      calcium hydroxide-containing pulp protective base (Dycal; Caulk Lab, Milford,
      DE). METHODS: Thirty-three permanent teeth (premolars, canines, and incisors) of
      3 miniature swine were used. Class V cavities were prepared on the buccal surface
      of teeth. The cavities were restored with Biodentine in the presence (control
      group) or absence (experimental group) of a Dycal protective base. The pulpal
      tissue responses were histologically and histomorphometrically assessed at
      postoperative periods of 3 and 8 weeks. Three specimens were further evaluated
      with scanning electron microscopy. The maximum thickness of the postoperatively
      formed mineralized matrix beneath the cavity floor was measured. Data were
      statistically analyzed by the Kruskal-Wallis and the Mann-Whitney U tests.
      RESULTS: A bacterial staining reaction along the cavity walls or intense
      inflammatory infiltration in the pulp was not detected in any of the specimens. A
      continuous zone of the postoperatively formed mineralized matrix mostly of
      atubular structure with scattered defects and cellular inclusions and
      occasionally followed by a thin zone with tubular morphology was detected in all
      specimens of the control group and 13 of 18 experimental group teeth. In the
      remaining teeth of the experimental group, a separate zone composed of the
      osteotypic mineralized matrix and soft tissues was noted between the circumpulpal
      and the newly formed matrix. Scanning electron microscopy confirmed the fibrous
      structural morphology of the tertiary dentin. A significantly higher rate of the
      postoperatively formed mineralized matrix had been formed in the teeth of the
      experimental group in both periods of 3 and 8 weeks (P < .01). CONCLUSIONS: The
      present investigation indicates that under the present experimental conditions
      tertiary dentin with occasional intermediate formation of osteodentin is observed
      after the application of Biodentine in the presence or absence of a Dycal
      protective base. The thickness of the tertiary dentine zone was significantly
      higher in the absence of Dycal.

PMID- 25956608
TI  - Expression and Distribution of Receptor Activator of Nuclear Factor Kappa B,
      Receptor Activator of Nuclear Factor Kappa B Ligand, and Osteoprotegerin in
      Periradicular Cysts.
AB  - INTRODUCTION: The receptor activator of nuclear factor kappa B (RANK)-RANK ligand
      (RANKL)-osteoprotegerin (OPG) system is important in osteoclastogenesis and may
      play a role in the development of apical periodontitis. This immunohistochemical
      study evaluated the distribution of the expression of these regulators of bone
      resorption in periradicular cysts. METHODS: Biopsy specimens from 40 consecutive
      periradicular cysts registered in the files of the Oral Pathology Laboratory were
      selected for the study on the basis of an initial analysis of archived
      histopathologic slides. Sections were stained with hematoxylin-eosin for
      preliminary analysis, and then silanized slides were used for immunohistochemical
      reactions with anti-RANK, anti-RANKL, and anti-OPG antibodies by the
      immunoperoxidase technique. The expression of these molecules in different tissue
      compartments and in the inflammatory infiltrate of cysts was compared. RESULTS:
      Analysis of the distribution of each marker in different areas of the cyst
      revealed no significant difference in the expression of RANK, RANKL, or OPG in
      areas of normal epithelium when compared with areas of hyperplastic epithelium.
      As for the connective tissue, higher expression of both RANK (P < .05) and RANKL
      (P < .05), but not OPG, was observed in the chronic inflammatory infiltrate, in
      comparison with the acute infiltrate. When the expression of the 3 molecules was
      compared per area of the cystic lesion, higher expression of RANK in comparison
      with OPG was verified in the areas of both normal and hyperplastic epithelium.
      RANKL was also significantly more expressed in the normal epithelium than OPG (P
      < .05). In the connective tissue, RANK expression was higher than OPG in both
      chronic and mixed infiltrates (P < .05) and also higher than RANKL expression in
      mixed infiltrate (P < .05). RANKL expression in chronic infiltrate was higher in
      comparison with OPG expression (P < .05). CONCLUSIONS: The results demonstrated
      that the type of inflammatory infiltrate present in periradicular cysts appears
      to influence the expression of RANK, RANKL, and OPG. The chronic infiltrate is
      likely to have increased osteolytic activity because of a higher RANKL/OPG ratio.

PMID- 25956609
TI  - Driver's behavioural changes with new intelligent transport system interventions
      at railway level crossings--A driving simulator study.
AB  - Improving safety at railway level crossings is an important issue for the
      Australian transport system. Governments, the rail industry and road
      organisations have tried a variety of countermeasures for many years to improve
      railway level crossing safety. New types of intelligent transport system (ITS)
      interventions are now emerging due to the availability and the affordability of
      technology. These interventions target both actively and passively protected
      railway level crossings and attempt to address drivers' errors at railway
      crossings, which are mainly a failure to detect the crossing or the train and
      misjudgement of the train approach speed and distance. This study aims to assess
      the effectiveness of three emerging ITS that the rail industry considers
      implementing in Australia: a visual in-vehicle ITS, an audio in-vehicle ITS, as
      well as an on-road flashing beacons intervention. The evaluation was conducted on
      an advanced driving simulator with 20 participants per trialled technology, each
      participant driving once without any technology and once with one of the ITS
      interventions. Every participant drove through a range of active and passive
      crossings with and without trains approaching. Their speed approach of the
      crossing, head movements and stopping compliance were measured. Results showed
      that driver behaviour was changed with the three ITS interventions at passive
      crossings, while limited effects were found at active crossings, even with
      reduced visibility. The on-road intervention trialled was unsuccessful in
      improving driver behaviour; the audio and visual ITS improved driver behaviour
      when a train was approaching. A trend toward worsening driver behaviour with the
      visual ITS was observed when no trains were approaching. This trend was not
      observed for the audio ITS intervention, which appears to be the ITS intervention
      with the highest potential for improving safety at passive crossings. 

PMID- 25956610
TI  - Impact of sleep difficulty on single and repeated injuries in adolescents.
AB  - Injuries are frequent and may be caused by sleep difficulty in youth. This study
      assessed the impact of sleep difficulty on single and repeated school and out-of
      school injuries and the confounding role of socioeconomic factors and school,
      behaviour and health-related difficulties among adolescents. The study population
      included 1559 middle-school adolescents from north-eastern France (mean age 13.5,
      SD 1.3) who completed at the end of school year a self-administered questionnaire
      to gather school and out-of-school injuries during the school year, and to assess
      sleep difficulty and previous injury risk factors which were socioeconomic
      factors (family structure, parents' education, father's occupation, and family
      income), school performance, obesity, alcohol/tobacco/cannabis/hard drugs use,
      health status, psychological health, and involvement-in-violence. For sleep
      difficulty and behaviour and health-related difficulties their first occurring
      over adolescent's life course was gathered. Multinomial logistic regression
      models were used retaining only sleep difficulty and other risk factors which had
      started before the school year (thus before the injuries studied). School and out
      of-school injuries and sleep difficulty were frequent. The adolescents with sleep
      difficulty without medical treatment had a higher risk of single school and out
      of-school injuries (gender-age-adjusted odds ratio gaOR 1.86 and 1.76,
      respectively) and a much higher risk of repeated school and out-of-school
      injuries (>=2 injuries; gaOR 2.43 and 3.73, respectively). The adolescents with
      persistent sleep difficulty despite a medical treatment also had a higher risk of
      single school and out-of-school injury (gaOR 2.31 and 1.78, respectively), and a
      much higher risk of repeated school and out-of-school injuries (gaOR 4.92 and
      4.36, respectively). Socioeconomic factors had a moderate contribution (<27%)
      while school, behaviour and health-related difficulties had a high contribution
      (reaching 71%) to the association between sleep difficulty and single/repeated
      injuries. The role of these factors differed between single/repeated school/out
      of-school injuries. Injury prevention should focus on screening and monitoring
      sleep difficulty and previous difficulties, especially among adolescents with
      socioeconomic difficulties, via physician-parent-school-adolescent
      collaborations. 

PMID- 25956611
TI  - Motivating patient adherence to allergic rhinitis treatments.
AB  - Patient nonadherence significantly burdens the treatment of allergic rhinitis
      (AR). Fewer than half of prescribed doses of intranasal corticosteroid medication
      are taken. The challenges for immunotherapies are even greater. While sustained
      treatment for 3 to 5 years is required for full benefit, most patients receiving
      immunotherapy, either subcutaneous or sublingual, stop treatment within the first
      year. Although research into interventions to improve AR adherence is lacking,
      lessons learned from adherence interventions in other chronic health conditions
      can be applied to AR. Two well-established, overriding models of care-the chronic
      care model and patient-centered care-can improve adherence. The patient-centered
      care model includes important lessons for allergy providers in their daily
      practice, including understanding and targeting modifiable barriers to adherence.
      Additionally, recent studies have begun to leverage health information and
      communication technologies to reach out to patients and promote adherence,
      extending patient-centered interventions initiated by providers during office
      visits.

PMID- 25956612
TI  - [Panniculitis of the thigh and lung emphysema in a 54-year-old patient].
AB  - This article reports a case of febrile, symmetrical and painful soft tissue
      swelling on both thighs in a 54-year-old otherwise healthy male patient.
      Histologically, necrotizing panniculitis of subcutaneous adipose tissue was
      described as a marker manifestation of a previously unknown alpha-1-antitrypsin
      (A1AT) deficiency with pulmonary emphysema and low plasma A1AT levels. The PiZZ
      homozygous form of A1AT could be diagnosed by gene sequencing. Complete remission
      of panniculitis could be achieved by A1AT replacement therapy. 

PMID- 25956614
TI  - Role of Chlamydia pneumoniae and Helicobacteria pylori in the development of
      tympanosclerosis.
AB  - The etiology of tympanosclerosis (TS) is not known, but TS commonly develops
      secondary to acute and chronic otitis media (COM). Since calcification process in
      TS resembles that of atherosclerosis (AS), pathogens that are related to
      pathogenesis of AS may be involved in development of TS. This prospective and
      controlled study, performed at a tertiary referral center, investigated a
      possible relationship between the presence of Chlamydia (C.) pneumoniae and
      Helicobacter (H.) pylori and the development of a tympanosclerotic plaque. The
      presence of C. pneumoniae was examined in the surgical specimens of 62 patients
      (29 females and 33 males; age range 10-70 years, mean age 30.8 +/- 13.3 years),
      including 30 patients with TS, 14 patients with cholesteatoma, and 18 patients
      with chronic suppurative otitis media (CSOM). The presence of H. pylori was
      examined in the surgical specimens of 88 patients (41 females and 47 males; age
      range 6-70 years, mean age 32.5 +/- 14.8 years), including 35 patients with TS,
      22 patients with cholesteatoma, 20 patients with CSOM, and 11 patients with
      otosclerosis. Tympanosclerotic plaques and control specimens from the
      cholesteatoma, polypoid mucosa, or mucosal portion of the perforations and stapes
      supra structure were examined for the presence of H. pylori and/or C. pneumoniae
      using real-time polymerase chain reaction analysis. The analysis demonstrated
      that specimens from the tympanosclerotic plaques and the other types of COM were
      all negative for C. pneumoniae and H. pylori. An association between C.
      pneumoniae or H. pylori infection and the development of TS or other types of COM
      could not be established.

PMID- 25956613
TI  - Comparative clinical study between the effect of fenofibrate alone and its
      combination with pentoxifylline on biochemical parameters and liver stiffness in
      patients with non-alcoholic fatty liver disease.
AB  - BACKGROUND: Non-alcoholic fatty liver disease is a common health problem
      associated with increased liver and vascular specific complications. AIM: The
      purpose of this study was to assess and compare the effect of fenofibrate alone
      or in combination with pentoxifylline on the measured biochemical parameters,
      inflammatory pathway and liver stiffness in patients with non-alcoholic fatty
      liver disease. METHODS: The study design was randomized controlled trial. From
      July 2013 to June 2014, we recruited 90 non-alcoholic fatty liver patients from
      the Internal Medicine Department at Tanta University Hospital, Egypt. They were
      classified randomly into two groups to receive fenofibrate 300 mg daily or
      fenofibrate 300 mg daily plus pentoxifylline 1200 mg/day in three divided doses
      for 24 weeks. Fasting blood sample was obtained before and 24 weeks after
      treatment for biochemical analysis of liver and lipid panels, tumor necrosis
      factor-alpha, hyaluronic acid, transforming growth factor beta 1, fasting plasma
      insulin and fasting glucose. Liver stiffness measurement was carried out using
      fibro-scan. Data were statistically analyzed by paired and unpaired Student's t
      test. RESULTS: The data obtained suggests that adding pentoxifylline to
      fenofibrate does not provide a beneficial effect on lipid panel, but has a
      beneficial effect on indirect biochemical markers of hepatic fibrosis, a direct
      marker linked to matrix deposition (hyaluronic acid), a cytokine/growth factor
      linked to liver fibrosis (transforming growth factor beta 1), the inflammatory
      pathway, insulin resistance and liver stiffness as compared to fenofibrate alone.
      CONCLUSION: The combination pentoxifylline plus fenofibrate may represent a new
      therapeutic strategy for non-alcoholic fatty liver disease as it resulted in more
      beneficial effects on direct and indirect markers of liver fibrosis, liver
      stiffness, insulin resistance and inflammatory pathway implicated in NAFLD.

PMID- 25956615
TI  - Delayed-onset hearing loss in pediatric candidates for cochlear implantation.
AB  - The objective of this study was to evaluate the clinical significance of delayed
      onset hearing loss in children. Seventy-three children who underwent cochlear
      implantation (CI) were included. They were divided into a congenital hearing loss
      group (n = 50) and a delayed-onset hearing loss group (n = 23). The age at
      diagnosis of hearing loss, age at the beginning of auditory habilitation, the age
      at CI, and the postimplant speech perception abilities were compared between the
      two groups. Children in the congenital hearing loss group were confirmed to have
      hearing loss at a mean age of 0.3 years, and those in the delayed-onset hearing
      loss group were diagnosed with hearing loss at a mean age of 2.0 years. Auditory
      habilitation began at a mean age of 0.4 and 2.0 years, and CI was performed at a
      mean age of 1.4 and 2.6 years, respectively. Children in the congenital hearing
      loss group had better scores on speech perception tests than those in the delayed
      onset hearing loss group, but the differences were not significant. About half of
      the children with delayed-onset hearing loss (57 %) had risk factors associated
      with delayed-onset hearing loss. A high prevalence of delayed-onset hearing loss
      was noted in the group of children who underwent CI. Risk factors for hearing
      loss were not found in 43 % of children with delayed-onset hearing loss.
      Universal screening for delayed-onset hearing loss needs to be performed during
      early childhood.

PMID- 25956616
TI  - The sensitivity and accuracy of a cone beam CT in detecting the chorda tympani.
AB  - The facial recess approach through posterior tympanotomy is the standard approach
      in cochlear implantation surgery. The size of the facial recess is highly
      variable, depending on the course of the chorda tympani. Despite their clinical
      importance, little is known about the sensitivity and accuracy of imaging studies
      in the detection of the chorda tympani. A total of 13 human temporal bones were
      included in this study. All of the temporal bones were submitted to a cone beam
      CT (Accuitomo, Morita, Japan). The multi-planar reconstruction images were
      rotated around the mastoid portion of the facial nerve to locate the branches of
      the facial nerve. A branch was diagnosed as the chorda tympani when it entered
      the tympanic cavity near the notch of Rivinus. The distance between the
      bifurcation and the tip of the short crus of the incus was measured. In all
      temporal bones, the canal of the chorda tympani or the posterior canaliculus was
      detected. In the CT-based evaluation, the average distance from the bifurcation
      to the incus short crus was 12.6 mm (8.3-15.8 mm). The actual distance after
      dissection was 12.4 mm (8.2-16.4 mm). The largest difference between the
      distances evaluated with the two procedures was 1.1 mm. Cone beam CT is very
      useful in detecting the course of the chorda tympani within the temporal bone.
      The measured distance is accurate.

PMID- 25956617
TI  - Ferulic acid regulates hepatic GLUT2 gene expression in high fat and fructose
      induced type-2 diabetic adult male rat.
AB  - GLUT2 is a bidirectional glucose transporter present in liver, kidney and
      pancreas. Studies have shown over-expression of GLUT2 in diabetic conditions.
      Ferulic acid (FA) is an antidiabetic phenolic phytocompound which is reported to
      regulate GLUT4 in vitro. The objective of our study is to evaluate the role of FA
      in the regulation of hepatic GLUT2 expression and the underlying mechanism. Male
      Wistar rats were divided into 5 groups: control, diabetic (diabetes was induced
      by giving high fat diet and high fructose water for 60 days), diabetic rats
      treated with FA (50mg/kg body weight/day, orally for 30 days), diabetic rats
      treated with metformin (50mg/kg body weight/day, orally for 30 days) and control
      rats treated with FA (50mg/kg body weight/day orally for 30 days). After 30 days
      treatment, animals were perfused and liver was dissected out. Glucose uptake and
      oxidation, expression of GLUT2 and binding of transcription factors - SREBP1c,
      HNF1alpha and HNF3beta with GLUT2 gene promoter were studied. Over-expression of
      GLUT2 in hepatic tissue was found in high fat and fructose- induced type-2
      diabetic animals. FA treatment reduced the GLUT2 expression in diabetic animals
      by impairing the interaction between these transcription factors (SREBP1c,
      HNF1alpha and HNF3beta) and GLUT2 gene promoter. 

PMID- 25956618
TI  - A concept ideation framework for medical device design.
AB  - Medical device design is a challenging process, often requiring collaboration
      between medical and engineering domain experts. This collaboration can be best
      institutionalized through systematic knowledge transfer between the two domains
      coupled with effective knowledge management throughout the design innovation
      process. Toward this goal, we present the development of a semantic framework for
      medical device design that unifies a large medical ontology with detailed
      engineering functional models along with the repository of design innovation
      information contained in the US Patent Database. As part of our development,
      existing medical, engineering, and patent document ontologies were modified and
      interlinked to create a comprehensive medical device innovation and design tool
      with appropriate properties and semantic relations to facilitate knowledge
      capture, enrich existing knowledge, and enable effective knowledge reuse for
      different scenarios. The result is a Concept Ideation Framework for Medical
      Device Design (CIFMeDD). Key features of the resulting framework include function
      based searching and automated inter-domain reasoning to uniquely enable
      identification of functionally similar procedures, tools, and inventions from
      multiple domains based on simple semantic searches. The significance and
      usefulness of the resulting framework for aiding in conceptual design and
      innovation in the medical realm are explored via two case studies examining
      medical device design problems. 

PMID- 25956619
TI  - Atom probe tomography of a Ti-Si-Al-C-N coating grown on a cemented carbide
      substrate.
AB  - The elemental distribution within a Ti-Si-Al-C-N coating grown by physical vapour
      deposition on a Cr-doped WC-Co cemented carbide substrate has been investigated
      by atom probe tomography. Special attention was paid to the coating/substrate
      interface region. The results indicated a diffusion of substrate binder phase
      elements into the Ti-N adhesion layer. The composition of this layer, and the Ti
      Al-N interlayer present between the adhesion layer and the main Ti-Si-Al-C-N
      layer, appeared to be sub-stoichiometric. The analysis of the interlayer showed
      the presence of internal surfaces, possibly grain boundaries, depleted in Al. The
      composition of the main Ti-Al-Si-C-N layer varied periodically in the growth
      direction; layers enriched in Ti appeared with a periodicity of around 30 nm.
      Laser pulsing resulted in a good mass resolution that made it possible to
      distinguish between N(+) and Si(2+) at 14 Da.

PMID- 25956620
TI  - Extracranial growth of glioblastoma multiforme.
AB  - We present a 59-year-old woman who noted an enlarging lump on her forehead 6
      months after a left frontotemporal craniotomy for tumor resection and
      chemoradiation of her primary glioblastoma multiforme (GBM). GBM is a highly
      aggressive intracranial neoplasm associated with the shortest survival time of
      any primary central nervous system malignancy. Extracranial metastasis is rare,
      especially without previous surgical disruption of the dura and calvarium, which
      has been postulated to cause seeding of the extracranial space with tumor cells.
      This patient's MRI revealed tumor recurrence for which she underwent repeat
      resection. Histopathology confirmed GBM with unmethylated O-6-methylguanine-DNA
      methyltransferase and wildtype isocitrate dehydrogenase 1 status, as well as
      tumor invasion through the bone and subdermal space. The genetic and molecular
      factors that predict extracranial invasion remain unclear and require further
      investigation. Emerging data on circulating tumor cells in GBM patients indicate
      that extraaxial metastasis may be part of the disease course in some,
      particularly in long term survivors. Furthermore, the proximity of calvarial and
      scalp lesions to previous surgical sites and the time course in which they emerge
      after surgery suggests that iatrogenic seeding may also play a role in
      metastasis. With heightened awareness of the phenomenon, surgical strategies such
      as watertight approximation of the dura, bone flap replacement, or changing
      surgical instruments once the intradural component is complete may prove useful
      to prevent seeding. Prophylactic craniospinal irradiation may also be an
      appropriate tool in patients at high risk for metastasis, although this
      population is difficult to identify.

PMID- 25956621
TI  - Galectin-3 in Atrial Fibrillation: A Novel Marker of Atrial Remodeling or Just
      Bystander?

PMID- 25956622
TI  - Comparison of Five-Year Outcome of Percutaneous Coronary Intervention With
      Coronary Artery Bypass Grafting in Triple-Vessel Coronary Artery Disease (from
      the Coronary Revascularization Demonstrating Outcome Study in Kyoto PCI/CABG
      Registry Cohort-2).
AB  - Studies evaluating long-term (>=5 years) outcomes of percutaneous coronary
      intervention (PCI) using drug-eluting stents compared with coronary artery bypass
      grafting (CABG) in patients with triple-vessel coronary artery disease (TVD) are
      still limited. We identified 2,978 patients with TVD (PCI: n = 1,824, CABG: n =
      1,154) of 15,939 patients with first coronary revascularization enrolled in the
      Coronary Revascularization Demonstrating Outcome Study in Kyoto PCI/CABG Registry
      Cohort-2. The primary outcome measure in the present analysis was a composite of
      death, myocardial infarction (MI), and stroke. Median follow-up duration for the
      surviving patients was 1,973 days (interquartile range 1,700 to 2,244). The
      cumulative 5-year incidence of death/MI/stroke was significantly higher in the
      PCI group than in the CABG group (28.2% vs 24.0%, log-rank p = 0.006). After
      adjusting for confounders, the excess risk of PCI relative to CABG for
      death/MI/stroke remained significant (hazard ratio [HR] 1.38, 95% confidence
      interval [CI] 1.13 to 1.68, p = 0.002). The excess risks of PCI relative to CABG
      for all-cause death, MI, and any coronary revascularization were also significant
      (HR 1.38, 95% CI 1.10 to 1.74, p = 0.006; HR 2.81, 95% CI 1.69 to 4.66, p <0.001;
      and HR 4.10, 95% CI 3.32 to 5.06, p <0.001, respectively). The risk for stroke
      was not significantly different between the PCI and CABG groups (HR 0.88, 95% CI
      0.61 to 1.26, p = 0.48). There were no interactions for the primary outcome
      measure between the mode of revascularization (PCI or CABG) and the subgroup
      factors such as age, diabetes, and Synergy Between PCI With Taxus and Cardiac
      Surgery score. In conclusion, CABG compared with PCI was associated with better
      long-term outcome in patients with TVD.

PMID- 25956623
TI  - Cardiac arrest in patients before and after the inception of takotsubo syndrome.

PMID- 25956624
TI  - Balancing the Risk of Bleeding and Stroke in Patients With Atrial Fibrillation
      After Percutaneous Coronary Intervention (from the AVIATOR Registry).
AB  - Patients with atrial fibrillation (AF) who underwent percutaneous coronary
      intervention (PCI) are at elevated risk for bleeding and thromboembolic ischemic
      events. Currently, guidelines on antithrombotic treatment for these patients are
      based on weak consensus. We describe patterns and determinants of antithrombotic
      prescriptions in this population. The Antithrombotic Strategy Variability in
      Atrial Fibrillation and Obstructive Coronary Disease Revascularized with PCI
      Registry was an international observational study of 859 consecutive patients
      with AF who underwent PCI from 2009 to 2011. Patients were stratified by
      treatment at discharge with either dual antiplatelet therapy (DAPT; aspirin plus
      clopidogrel) or triple therapy (TT; warfarin plus DAPT). Bleeding and
      thromboembolism risks were assessed by the HAS-BLED and CHADS2 scores,
      respectively, and predictors of TT prescription at discharge were identified.
      Major adverse cardiovascular events and clinically relevant bleeding (Bleeding
      Academic Research Consortium score >=2) at 1-year follow-up were compared across
      antithrombotic regimens. Compared with patients on DAPT (n = 488; 57%), those
      given TT (n = 371; 43%) were older, with higher CHADS2 scores, lower left
      ventricular ejection fraction, and more often had permanent AF, single-vessel
      coronary artery disease, and bare-metal stents. In multivariate analysis,
      increasing thromboembolic risk (CHADS2) was associated with a higher rate of TT
      prescription at discharge (intermediate vs low CHADS2: odds ratio 2.2, 95%
      confidence interval [CI] 2.0 to 3.3, p <0.01; high vs low CHADS2: odds ratio 1.6,
      95% CI 2.6 to 4.3, p <0.01 for TT). However, there was no significant association
      between bleeding risk and TT prescription in the overall cohort or within each
      CHADS2 risk stratum. The rates of major adverse cardiovascular events were
      similar for patients discharged on TT or DAPT (20% vs 17%, adjusted hazard ratio
      0.8, 95% CI 0.5 to 1.1, p = 0.19), whereas the rate of Bleeding Academic Research
      Consortium >=2 bleeding was higher in patients discharged on TT (11.5% vs 6.4%,
      adjusted hazard ratio 1.8, 95% CI 1.1 to 2.9, p = 0.02). In conclusion, the
      choice of the intensity of antithrombotic therapy correlated more closely with
      the risk of ischemic rather than bleeding events in this cohort of patients with
      AF who underwent PCI.

PMID- 25956625
TI  - Reply: To PMID 25604929.

PMID- 25956626
TI  - Single-Nucleotide Polymorphisms of Tight Junction Component Claudin-1 Associated
      with Leukoaraiosis.
AB  - BACKGROUND: The blood-brain barrier (BBB) plays a major role in the development
      of leukoaraiosis (LA). The junctional complex of BBB consists of tight junction
      (TJ) and adherens junction (AJ). Claudin-1 is the integral component of TJ. The
      aim of this study was to evaluate whether genetic variations in claudin-1 gene
      are associated with the development of LA. METHODS: LA has to be diagnosed based
      on images. A total of 228 LA cases and 203 controls were enrolled from the
      individuals who underwent brain magnetic resonance imaging with obtainable
      vascular risk factors. Genotyping of claudin-1 single-nucleotide polymorphisms
      (SNPs) (rs17501010, rs893051, and rs9290927) was performed by real-time
      polymerase chain reaction with LightSNiP reagents (coupled primer and probe) and
      FastStart DNAMaster HybProbe (Roche Diagnostic, GmBH, Mannheim, Germany) in
      LightCycler 2.0. RESULTS: Among the 3 SNPs of claudin-1, a significant genetic
      difference was found only between control and LA (both LA-periventricular white
      matter [PVWM] and LA-subcortical deep white matter) with SNP rs9290927. However,
      their haplotypes G-G-T and G-C-A were significantly different between LA-PVWM and
      control, which increase the development of LA-PVWM with odds ratios of 1.45 and
      .57, respectively. CONCLUSIONS: This study demonstrated first evidence of genetic
      polymorphism of TJ component claudin-1 and their haplotypes associated with LA.

PMID- 25956627
TI  - Surgical Outcomes for Cervical Carotid Artery Stenosis: Treatment Strategy for
      Bilateral Cervical Carotid Artery Stenosis.
AB  - BACKGROUND: Carotid endarterectomy (CEA) and carotid stenting (CAS) are
      beneficial procedures for patients with high-grade cervical carotid stenosis.
      However, it is sometimes difficult to manage patients with bilateral carotid
      stenosis. To decide the treatment strategy, one of the most important questions
      is whether contralateral stenosis increases the risk of patients undergoing CEA.
      METHODS: This retrospective study included 201 patients with carotid stenosis who
      underwent a total of 219 consecutive procedures (CEA 189/CAS 30). We
      retrospectively analyzed outcomes in patients with carotid stenosis who were
      treated with either CEA or CAS and evaluated whether or not contralateral lesions
      increases the risk of patients undergoing CEA or CAS. Furthermore, we
      retrospectively verified our treatment strategy for bilateral carotid stenosis.
      RESULTS: The incidences of perioperative complications were 5.3% in the CEA
      patients and 6.7% in the CAS patients, respectively. There was no significant
      difference between these 2 groups. The existences of contralateral occlusion
      and/or contralateral stenosis were not associated with perioperative
      complications in both the groups. There were 32 patients with bilateral severe
      carotid stenosis (>50%). Of those, 13 patients underwent bilateral
      revascularizations; CEA followed by CEA in 8, CEA followed by CAS in 3, CAS
      followed by CEA + coronary artery bpass grafting in 1, and CAS followed by CAS in
      1. CONCLUSIONS: Our date showed that the existence of contralateral carotid
      lesion was not associated with perioperative complications, and most of our cases
      with bilateral carotid stenosis initially underwent CEA.

PMID- 25956628
TI  - Cardiovascular disease and sudden cardiac death: between genetics and genomics.

PMID- 25956629
TI  - Auditory P300 as a predictor of short-term prognosis in subjects at clinical high
      risk for psychosis.
AB  - BACKGROUND: The aim of this study was to investigate whether P300 could predict
      the short-term prognosis of subjects at clinical high risk (CHR) for psychosis
      who do not convert to psychotic disorder (non-converters). METHOD: CHR subjects
      were examined with auditory P300 at baseline, and their clinical state was
      regularly assessed up to 2 years. 45 CHR non-converters were divided into
      remitter and non-remitter groups. Repeated-measures analysis of variance (ANOVA)
      was performed to compare baseline P300 between the two groups. Multiple
      regression analysis was used to identify factors predicting symptomatic or
      functional improvement in CHR subjects during the follow-up period. RESULTS:
      There were no group differences in P300 amplitude or latency between CHR
      remitters and non-remitters. In the multiple regression analysis, P300 amplitude
      at Pz (beta=0.206, 95% confidence interval [95CI]=0.035 to 0.567, p=0.028)
      significantly predicted later amelioration of the Scale of Prodromal Symptoms
      (SOPS) negative symptoms. Improvement in SOPS general symptoms was significantly
      predicted by P300 amplitude at Pz (beta=0.255, 95CI=0.065 to 0.455, p=0.010) and
      mood stabilizer use (beta=0.199, 95CI=0.081 to 4.154, p=0.042). CONCLUSIONS:
      These results indicate that P300 may be a possible predictor of improvement in
      negative and general symptoms in CHR non-converters. Our findings support the
      recommendation that a broader concept of assessment guidelines is needed to
      forecast clinical outcome and provide appropriate interventions for CHR non
      converters.

PMID- 25956631
TI  - Language as a biomarker in those at high-risk for psychosis.

PMID- 25956632
TI  - Response to: NMDA hypofunction attenuates driver inputs in higher order thalamic
      nuclei: An alternative view.

PMID- 25956630
TI  - Protein expression of targets of the FMRP regulon is altered in brains of
      subjects with schizophrenia and mood disorders.
AB  - Fragile X mental retardation protein (FMRP) is an RNA binding protein with 842
      target mRNAs in mammalian brain. Silencing of the fragile X mental retardation 1
      (FMR1) gene leads to loss of expression of FMRP and upregulated metabotropic
      glutamate receptor 5 (mGluR5) signaling resulting in the multiple physical and
      cognitive deficits associated with fragile X syndrome (FXS). Reduced FMRP
      expression has been identified in subjects with autism, schizophrenia, bipolar
      disorder, and major depression who do not carry the mutation for FMR1. Our
      laboratory has recently demonstrated altered expression of four downstream
      targets of FMRP-mGluR5 signaling in brains of subjects with autism: homer 1,
      amyloid beta A4 precursor protein (APP), ras-related C3 botulinum toxin substrate
      1 (RAC1), and striatal-enriched protein tyrosine phosphatase (STEP). In the
      current study we investigated the expression of the same four proteins in lateral
      cerebella of subjects with schizophrenia, bipolar disorder, and major depression
      and in frontal cortex of subjects with schizophrenia and bipolar disorder. In
      frontal cortex we observed: 1) reduced expression of 120 kDa form of APP in
      subjects with schizophrenia and bipolar disorder; 2) reduced expression of 61 kDa
      and 33k Da forms of STEP in subjects with schizophrenia; 3) reduced expression of
      88 kDa form of APP in subjects with bipolar disorder; and 3) trends for reduced
      expression of 88 kDa form of APP and homer 1 in subjects with schizophrenia and
      bipolar disorder, respectively. In lateral cerebella there was no group
      difference, however we observed increased expression of RAC1 in subjects with
      bipolar disorder, and trends for increased RAC1 in subjects with schizophrenia
      and major depression. Our results provide further evidence that proteins involved
      in the FMRP-mGluR5 signaling pathway are altered in schizophrenia and mood
      disorders.

PMID- 25956633
TI  - Inflammatory markers are associated with general cognitive abilities in
      schizophrenia and bipolar disorder patients and healthy controls.
AB  - BACKGROUND: The mechanisms underlying cognitive impairment in schizophrenia and
      bipolar disorders are largely unknown. Immune abnormalities have been found in
      both disorders, and inflammatory mediators may play roles in cognitive function.
      We investigated if inflammatory markers are associated with general cognitive
      abilities. METHODS: Participants with schizophrenia spectrum (N=121) and bipolar
      spectrum (N=111) disorders and healthy controls (N=241) were included. General
      intellectual abilities were assessed using the Wechsler Abbreviated Scale of
      Intelligence (WASI). Serum concentrations of the following immune markers were
      measured: Soluble tumor necrosis factor receptor 1 (sTNF-R1), interleukin 1
      receptor antagonist (IL-1Ra), osteoprotegerin, von Willebrand factor, C-reactive
      protein, interleukin-6 and CD40 ligand. RESULTS: After adjusting for age, sex and
      diagnostic group, significant negative associations with general cognitive
      function were found for sTNF-R1 (p=2*10(-5)), IL-1Ra (p=0.002) and sCD40 ligand
      (p=0.003). Among patients, the associations remained significant (p=0.006,
      p=0.005 and p=0.02) after adjusting for possible confounders including education,
      smoking, psychotic and affective symptoms, body mass index, cortisol, medication
      and time of blood sampling. Subgroup analysis, showed that general cognitive
      abilities were significantly associated with IL-1Ra and sTNF-R1 in schizophrenia
      patients, with sCD40L and IL-1Ra in bipolar disorder patients and with sTNF-R1 in
      healthy controls. CONCLUSION: The study shows significant negative associations
      between inflammatory markers and general cognitive abilities after adjusting for
      possible confounders. The findings strongly support a role for inflammation in
      the neurophysiology of cognitive impairment.

PMID- 25956634
TI  - Jumping to conclusions and the persistence of delusional beliefs in first episode
      psychosis.
AB  - BACKGROUND: Cognitive biases may contribute to delusion persistence. We tested
      this in a longitudinal study of first episode psychosis (FEP). METHODS: 34 FEP
      patients completed assessments of delusions and Jumping to Conclusions (JTC) at
      baseline and 12-month follow-up. RESULTS: JTC was associated with baseline
      delusion severity (t(32)=2.7, p=0.01). Baseline delusions persisted at follow-up
      for 8/20 participants (40%), who all jumped to conclusions (8/8, 100%), compared
      to half of those with no or changeable delusions (14/26, 54%; chi(2) (df=1)=5.7,
      p=0.03; Phi=0.4). CONCLUSION: Findings implicate cognitive biases in delusion
      persistence, and support the potential to reduce delusions through reasoning
      focused interventions.

PMID- 25956635
TI  - The influence of endoparasites on selected production parameters in pigs in
      various housing systems.
AB  - The aim of the study was to determine the level of lean meat content and daily
      gains of 400 fatteners infected by endoparasites and kept in two systems (shallow
      and deep litter). Slaughter evaluation of the pigs was conducted according to the
      EUROP carcass classification. In order to evaluate the average daily gains (g)
      during finishing period, body weights were investigated twice: at the beginning
      and at the end of the finishing period. The housing system affected the presence
      of Ascaris suum and Oesophagostomum spp. Infestation was found to be higher on
      shallow than on deep litter, and it significantly affected selected fattening and
      slaughter parameters of the fatteners. Infected animals were characterized by
      gains approximately 60 g lower than those of uninfected ones, while meatiness was
      higher in fatteners which were not infected at the end of the fattening period
      compared to animals with parasites (55.2% vs. 52.0%). 

PMID- 25956636
TI  - Serum DHEA-S increases in dogs naturally infected with Ehrlichia canis.
AB  - Adrenocortical disturbances are expected in canine ehrlichiosis due to the
      immunological challenges caused by infection and consequent inflammation. Thus,
      this study aimed to evaluate the occurrence of adrenocortical hormonal
      alterations in dogs naturally infected with Ehrlichia canis (n = 21) as
      positively confirmed by the presence of anti-E. canis antibodies (Dot-ELISA) and
      nested PCR (nPCR). Serum dehydroepiandrosterone sulfate (DHEA-S) concentrations
      were assessed via ELISA before and one hour after ACTH stimulation. Another 10
      healthy dogs were subjected to the same stimulation protocol and used as
      controls. The results revealed that baseline and post-ACTH DHEA-S concentrations
      were significantly greater in sick dogs, regardless of gender, and this finding
      illustrates the stress induced by naturally acquired ehrlichiosis in dogs. 

PMID- 25956637
TI  - Characterization of antigen-presenting cells from the porcine respiratory system.
AB  - Antigen-presenting cells (APCs) are strategically placed in all anatomic sites
      with high antigen exposure such as the respiratory system. The aim of this study
      was to evaluate phenotypic and functional properties of APCs from the lung (L
      Cs), mediastinal lymph node (LN-Cs) and bronchoalveolar lavage cells (BAL-Cs).
      The APCs were first analyzed based on forward scatter and side scatter profiles
      and the selection of MHC-II(high)CD172a(+) cells (referred to as APCs); then the
      expression of CD1a, CD163, CD206, CD16 and CD11R3 was evaluated in the APCs. The
      results showed that CD1a, CD163 and CD206 were differentially expressed among L
      Cs, LN-Cs and BAL-Cs, suggesting the phenotype MHC-II(high)CD172a(+)CD1a(low/
      )CD163(low)CD206(-) for L-Cs and MHC-II(high)CD172a(+)CD1a(+)CD163(low/-)CD206(+)
      for LN-Cs. BAL-Cs were MHC-II(high)CD172a(+)CD1a(-)CD163(high)CD206(+/-). The
      functional characteristics of L-Cs and LN-Cs were different from those of BAL-Cs,
      confirming that L-Cs and LN-Cs resemble specialized APCs. In conclusion, we
      present the characterization of APCs from L-Cs, LN-Cs and BAL-Cs of the porcine
      respiratory system. 

PMID- 25956638
TI  - Interactions between Microcystis aeruginosa and coexisting amoxicillin
      contaminant at different phosphorus levels.
AB  - Microcystis aeruginosa was cultured with 0.05-5 mg L(-1) of phosphorus and
      exposed to 200-500 ng L(-1) of amoxicillin for seven days. Amoxicillin presented
      no significant effect (p>0.05) on the growth of M. aeruginosa at phosphorus
      levels of 0.05 and 0.2 mg L(-1), but stimulated algal growth as a hormesis effect
      at phosphorus levels of 1 and 5 mg L(-1). Phosphorus and amoxicillin affected the
      contents of chlorophyll-a, adenosine triphosphate (ATP) and malondialdehyde, the
      expression of psbA and rbcL, as well as the activities of adenosinetriphosphatase
      and glutathione S-transferase in similar manners, but regulated the production
      and release of microcystins and the activities of superoxide dismutase and
      peroxidase in different ways. Increased photosynthesis activity was related with
      the ATP consumption for the stress response to amoxicillin, and the stress
      response was enhanced as the phosphorus concentration increased. The
      biodegradation of amoxicillin by M. aeruginosa increased from 11.5% to 28.2% as
      the phosphorus concentration increased. Coexisting amoxicillin aggravated M.
      aeruginosa pollution by increasing cell density and concentration of
      microcystins, while M. aeruginosa alleviated amoxicillin pollution via
      biodegradation. The interactions between M. aeruginosa and amoxicillin were
      significantly regulated by phosphorus (p<0.05) and led to a complicated situation
      of combined pollution.

PMID- 25956639
TI  - Titanium dioxide nanoparticles modulate the toxicological response to cadmium in
      the gills of Mytilus galloprovincialis.
AB  - We investigated the influence of titanium dioxide nanoparticles (nano-TiO2) on
      the response to cadmium in the gills of the marine mussel Mytilus
      galloprovincialis in terms of accumulation and toxicity. Mussels were in vivo
      exposed to nano-TiO2, CdCl2, alone and in combination. Several cellular
      biomarkers were investigated in gills: ABC transport proteins and
      metallothioneins at gene/protein (abcb1, abcc-like and mt-20) and functional
      level, GST activity, NO production and DNA damage (Comet assay). Accumulation of
      total Cd and titanium in gills as in whole soft tissue was also investigated.
      Significant responses to Cd exposure were observed in mussel gills as up
      regulation of abcb1 and mt-20 gene transcription, increases in total MT content,
      P-gp efflux and GST activity, DNA damage and NO production. Nano-TiO2 alone
      increased P-gp efflux activity and NO production. When combined with Cd, nano
      TiO2 reduced the metal-induced effects by significantly lowering abcb1 gene
      transcription, GST activity, and DNA damage, whereas, additive effects were
      observed on NO production. A lower concentration of Cd was observed in the gills
      upon co-exposure, whereas, Ti levels were unaffected. A competitive effect in
      uptake/accumulation of nano-TiO2 and Cd seems to occur in gills. A confirmation
      is given by the observed absence of adsorption of Cd onto nano-TiO2 in sea water
      media. 

PMID- 25956640
TI  - Selective preparation of zeolite X and A from flyash and its use as catalyst for
      biodiesel production.
AB  - This work discusses the utilization of flyash for synthesis of heterogeneous
      catalyst for transesterification. Different types of zeolites were synthesized
      from alkali fusion followed by hydrothermal treatment of coal flyash as source
      material. The synthesis conditions were optimized to obtain highly crystalline
      zeolite based on degree of crystallinity and cation exchange capacity (CEC). The
      effect of CEC, acid treatment, Si/Al ratio and calcination temperature (800, 900
      and 1000  degrees C) on zeolite formation was also studied. Pure, single phase
      and highly crystalline zeolite was obtained at flyash/NaOH ratio (1:1.2), fusion
      temperature (550  degrees C), fusion time (1 h), hydrothermal temperature (110 
      degrees C) and hydrothermal time (12h). The synthesized zeolite was ion-exchanged
      with potassium and was used as catalyst for transesterification of mustard oil to
      obtain a maximum conversion of 84.6% with 5 wt% catalyst concentration, 12:1
      methanol to oil molar ratio, reaction time of 7 h at 65  degrees C. The catalyst
      was reused for 3 times with marginal reduction in activity.

PMID- 25956641
TI  - Continuous removal of zinc from wastewater and mine dump leachate by a microalgal
      biofilm PSBR.
AB  - Bio-removal of heavy metals from wastewater by microalgae has been investigated
      for decades. However, technical and economical limitations of cultivation systems
      for microalgae still impair progress toward application. Recently, a novel type
      of bioreactor for (immobilized) biofilm cultivation, the Porous Substrate
      Bioreactor (PSBR), has been shown to optimize biomass feedstock production and
      harvest, offering novel possibilities for application in the treatment of
      wastewater. We used two types of laboratory-scale Twin-Layer PSBRs to remove zinc
      (2-3 mg Zn L(-1)) from synthetic wastewater and real mine dump leachate in a
      continuous and batch process. The selection and use of a biofilm of a Zn
      resistant strain of the green alga Stichococcus bacillaris (EC50 of 28.9 mg Zn L(
      1) based on Pulse-amplitude modulated (PAM) chlorophyll fluorescence analysis)
      led to a high zinc absorption capacity of 15-19 mg Z ng(-1) algal dry matter. The
      removal capacity for zinc correlated positively with biomass production and was
      thus, light dependent. Bio-removal properties observed here combined with biomass
      productivities of PSBR systems compare favorably with other algal-based bio
      sorption technologies.

PMID- 25956642
TI  - Trihalomethanes (THMs) precursor fractions removal by coagulation and adsorption
      for bio-treated municipal wastewater: Molecular weight, hydrophobicity/hydrophily
      and fluorescence.
AB  - Due to concerns over health risk of disinfection byproducts (DBPs), removal of
      trihalomethanes (THMs) precursor from bio-treated wastewater by coagulation and
      adsorption was investigated in this study. Ultrafiltration (UF) membranes and
      nonionic resins were applied to fractionate THMs precursor into various molecular
      weight (MW) fractions and hydrophobic/hydrophilic fractions. Characteristics of
      coagulated water and adsorbed water were evaluated by the three-dimensional
      excitation and emission matrix (3DEEM) fluorescence spectroscopy. Results showed
      that coagulation and adsorption were suitable for removing different
      hydrophobic/hydrophilic and fluorescent fractions. Coagulation decreased THMs
      concentration in hydrophobic acids (HoA) fraction from 59 MUg/L to 39 MUg/L,
      while the lowest THMs concentration (9 MUg/L) in hydrophilic substances (HiS)
      fraction was obtained in adsorbed water. However, both coagulation and adsorption
      were ineffective for removing fractions with MW<5 kDa. Although coagulation and
      adsorption processes could reduce THMs formation, some specific THMs formation
      potential (STHMFP) in residual dissolved organic matter (DOM) fractions increased
      in this study. Hydrophobic acid and hydrophilic fractions increased after
      coagulation treatment, and low MW and hydrophobic fractions increased after
      adsorption treatment. In addition, active carbon adsorbed more organic matter
      than coagulant, but brominated disinfection byproducts (Br-DBPs) in adsorbed
      water turned to the major THMs species after chlorination.

PMID- 25956643
TI  - Effect of clay minerals and nanoparticles on chromium fractionation in soil
      contaminated with leather factory waste.
AB  - This study was conducted to investigate the effect of time, clay minerals and
      nanoparticles (NPs) on chromium (Cr) fractionation in a soil contaminated with
      leather factory waste (LFW). Soil was mixed with LFW, then, the contaminated
      soils were treated with clay minerals (bentonite and zeolite) and nanoparticles
      (MgO, TiO2 and ZnO) at 5% and 1%, respectively. The samples were incubated for 15
      180 days at 25  degrees C and constant moisture. After incubation, Cr in control
      and treated soils was fractionated by the sequential extraction procedure. The
      distribution of various Cr fractions in control soil indicated that the greatest
      amounts of Cr were found in the residual fraction (RES) followed by the carbonate
      (CAR), organic matter (OM) and exchangeable (EXC) fractions. The addition of LFW
      in soils increased Cr concentration in all fractions. The higher proportion of
      EXC fraction in the soil treated with LFW indicates its higher potential of
      leaching and runoff transport. In all treated soils, the RES fraction was
      increased, while EXC and OM fractions were decreased during incubation. The
      results indicated that NPs are effective adsorbent for the removal of Cr ions
      from LFW treated soil, and they could be useful in reducing their environment
      risk.

PMID- 25956644
TI  - Co-sequestration of Zn(II) and phosphate by gamma-Al2O3: From macroscopic to
      microscopic investigation.
AB  - Little information is available concerning co-sorbing oxyanion and metal
      contaminants in the environment, yet in most metal-contaminated areas, co
      contamination by phosphate is common. In this study, the mutual effects of
      phosphate and Zn(II) on their interaction with gamma-Al2O3 are investigated by
      batch experiments and X-ray absorption fine structure spectroscopy (XAFS)
      technique. The results show that the co-sorption of phosphate on gamma-Al2O3
      modifies both the extent of Zn(II) sorption and the local atomic structures of
      sorbed Zn(II) ions. Multiple mechanisms are involved in Zn(II) retention in the
      presence of phosphate, including electrostatic interaction, binary and ternary
      surface complexation, and the formation of Zn(II)-phosphate polynuclear
      complexes. At pH 6.5, type III ternary surface complexation occurs concurrently
      with binary Zn-alumina surface complexation at low phosphate concentrations,
      whereas the formation of type III ternary surface complexes is promoted as the
      phosphate concentration increases. With further increasing phosphate
      concentration, Zn(II)-phosphate polynuclear complexes are formed. At pH 8.0, Zn
      dominantly forms type III ternary surface complexes in the presence of phosphate.
      The results of this study indicate the variability of Zn complexation on oxide
      surface and the importance of combining macroscopic observations with XAFS
      capable of determining metal complex formation mechanism for ternary system. 

PMID- 25956645
TI  - Pro-inflammatory responses of RAW264.7 macrophages when treated with ultralow
      concentrations of silver, titanium dioxide, and zinc oxide nanoparticles.
AB  - To cellular systems, nanoparticles are considered as foreign particles. Upon
      particles and cells contact, innate immune system responds by activating the
      inflammatory pathway. However, excessive inflammation had been linked to various
      diseases ranging from allergic responses to cancer. Common nanoparticles, namely
      silver, titanium dioxide, and zinc oxide exist in the environment as well as in
      consumer products at ultralow level of 10(-6)-10(-3) MUg mL(-1). However, so far
      the risks of such low NPs concentrations remain unexplored. Therefore, we
      attempted to screen the pro-inflammatory responses after ultralow concentration
      treatments of the three nanoparticles on RAW264.7 macrophages, which are a part
      of the immune system, at both cellular and gene levels. Even though cytotoxicity
      was only observed at nanoparticles concentrations as high as 10 MUg mL(-1),
      through the level of NF-kappaB and upregulation of pro-inflammatory genes, we
      observed activation of the induction of genes encoding pro-inflammatory cytokines
      starting already at 10(-7) MUg mL(-1). This calls for more thorough
      characterization of nanoparticles in the environment as well as in consumer
      products to ascertain the health and safety of the consumers and living systems
      in general.

PMID- 25956646
TI  - Plasma filtering techniques for nuclear waste remediation.
AB  - Nuclear waste cleanup is challenged by the handling of feed stocks that are both
      unknown and complex. Plasma filtering, operating on dissociated elements, offers
      advantages over chemical methods in processing such wastes. The costs incurred by
      plasma mass filtering for nuclear waste pretreatment, before ultimate disposal,
      are similar to those for chemical pretreatment. However, significant savings
      might be achieved in minimizing the waste mass. This advantage may be realized
      over a large range of chemical waste compositions, thereby addressing the
      heterogeneity of legacy nuclear waste. 

PMID- 25956647
TI  - Cement kiln dust (CKD)-filter sand permeable reactive barrier for the removal of
      Cu(II) and Zn(II) from simulated acidic groundwater.
AB  - The hydraulic conductivity and breakthrough curves of copper and zinc
      contaminants were measured in a set of continuous column experiments for 99 days
      using cement kiln dust (CKD)-filter sand as the permeable reactive barrier. The
      results of these experiments proved that the weight ratios of the cement kiln
      dust-filter sand (10:90 and 20:80) are adequate in preventing the loss of
      reactivity and hydraulic conductivity and, in turn, avoiding reduction in the
      groundwater flow. These results reveal a decrease in the hydraulic conductivity,
      which can be attributed to an accumulation of most of the quantity of the
      contaminant masses in the first sections of the column bed. Breakthrough curves
      for the description of the temporal contaminant transport within the barrier were
      found to be more representative by the Belter-Cussler-Hu and Yan models based on
      the coefficient of determination and Nash-Sutcliffe efficiency. The longevity of
      the barrier was simulated for the field scale, based on the laboratory column
      tests and the values verified that cement kiln dust can be effectively used in
      the future, as the reactive material in permeable reactive barrier technology.
      These results signify that the longevity of the barrier is directly proportional
      to its thickness and inversely to the percentage of the CKD used. 

PMID- 25956648
TI  - Translocation of uranium from water to foodstuff while cooking.
AB  - The present work report the unusual uranium uptake by foodstuff, especially those
      rich in carbohydrates like rice when they are cooked in water, contaminated with
      uranium. The major staple diet in South Asia, rice, was chosen to study its
      interaction with UO2(2+), the active uranium species in water, using inductively
      coupled plasma mass spectrometry. Highest uptake limit was checked by cooking
      rice at very high uranium concentration and it was found to be good scavenger of
      uranium. To gain insight into the mechanism of uptake, direct interaction of
      UO2(2+) with monosaccharides was also studied, using electrospray ionization mass
      spectrometry taking mannose as a model. The studies have been done with dissolved
      uranium salt, uranyl nitrate hexahydrate (UO2(NO3)2.6H2O), as well as the
      leachate of a stable oxide of uranium, UO2(s), both of which exist as UO2(2+) in
      water. Among the eight different rice varieties investigated, Karnataka Ponni
      showed the maximum uranium uptake whereas unpolished Basmati rice showed the
      minimum. Interaction with other foodstuffs (potato, carrot, peas, kidney beans
      and lentils) with and without NaCl affected the extent of chemical interaction
      but was not consistent with the carbohydrate content. Uranium interaction with D
      mannose monitored through ESI-MS, under optimized instrumental parameters,
      identified the peaks corresponding to uranyl adduct with mannose monomer, dimer
      and trimer and the species were confirmed by MS/MS studies. The product ion mass
      spectra showed peaks illustrating water loss from the parent ion as the collision
      energy was increased, an evidence for the strong interaction of uranium with
      mannose. This study would constitute the essential background for understanding
      interaction of uranium with various foods. Extension of this work would involve
      identification of foodstuff as green heavy metal scavengers.

PMID- 25956649
TI  - Assembly constraints drive co-evolution among ribosomal constituents.
AB  - Ribosome biogenesis, a central and essential cellular process, occurs through
      sequential association and mutual co-folding of protein-RNA constituents in a
      well-defined assembly pathway. Here, we construct a network of co-evolving
      nucleotide/amino acid residues within the ribosome and demonstrate that assembly
      constraints are strong predictors of co-evolutionary patterns. Predictors of co
      evolution include a wide spectrum of structural reconstitution events, such as
      cooperativity phenomenon, protein-induced rRNA reconstitutions, molecular packing
      of different rRNA domains, protein-rRNA recognition, etc. A correlation between
      folding rate of small globular proteins and their topological features is known.
      We have introduced an analogous topological characteristic for co-evolutionary
      network of ribosome, which allows us to differentiate between rRNA regions
      subjected to rapid reconstitutions from those hindered by kinetic traps.
      Furthermore, co-evolutionary patterns provide a biological basis for deleterious
      mutation sites and further allow prediction of potential antibiotic targeting
      sites. Understanding assembly pathways of multicomponent macromolecules remains a
      key challenge in biophysics. Our study provides a 'proof of concept' that
      directly relates co-evolution to biophysical interactions during multicomponent
      assembly and suggests predictive power to identify candidates for critical
      functional interactions as well as for assembly-blocking antibiotic target sites.

PMID- 25956650
TI  - YeastFab: the design and construction of standard biological parts for metabolic
      engineering in Saccharomyces cerevisiae.
AB  - It is a routine task in metabolic engineering to introduce multicomponent
      pathways into a heterologous host for production of metabolites. However, this
      process sometimes may take weeks to months due to the lack of standardized
      genetic tools. Here, we present a method for the design and construction of
      biological parts based on the native genes and regulatory elements in
      Saccharomyces cerevisiae. We have developed highly efficient protocols (termed
      YeastFab Assembly) to synthesize these genetic elements as standardized
      biological parts, which can be used to assemble transcriptional units in a single
      tube reaction. In addition, standardized characterization assays are developed
      using reporter constructs to calibrate the function of promoters. Furthermore,
      the assembled transcription units can be either assayed individually or applied
      to construct multi-gene metabolic pathways, which targets a genomic locus or a
      receiving plasmid effectively, through a simple in vitro reaction. Finally, using
      beta-carotene biosynthesis pathway as an example, we demonstrate that our method
      allows us not only to construct and test a metabolic pathway in several days, but
      also to optimize the production through combinatorial assembly of a pathway using
      hundreds of regulatory biological parts. 

PMID- 25956651
TI  - PockDrug-Server: a new web server for predicting pocket druggability on holo and
      apo proteins.
AB  - Predicting protein pocket's ability to bind drug-like molecules with high
      affinity, i.e. druggability, is of major interest in the target identification
      phase of drug discovery. Therefore, pocket druggability investigations represent
      a key step of compound clinical progression projects. Currently computational
      druggability prediction models are attached to one unique pocket estimation
      method despite pocket estimation uncertainties. In this paper, we propose
      'PockDrug-Server' to predict pocket druggability, efficient on both (i) estimated
      pockets guided by the ligand proximity (extracted by proximity to a ligand from a
      holo protein structure) and (ii) estimated pockets based solely on protein
      structure information (based on amino atoms that form the surface of potential
      binding cavities). PockDrug-Server provides consistent druggability results using
      different pocket estimation methods. It is robust with respect to pocket boundary
      and estimation uncertainties, thus efficient using apo pockets that are
      challenging to estimate. It clearly distinguishes druggable from less druggable
      pockets using different estimation methods and outperformed recent druggability
      models for apo pockets. It can be carried out from one or a set of apo/holo
      proteins using different pocket estimation methods proposed by our web server or
      from any pocket previously estimated by the user. PockDrug-Server is publicly
      available at: http://pockdrug.rpbs.univ-paris-diderot.fr. 

PMID- 25956653
TI  - xVis: a web server for the schematic visualization and interpretation of
      crosslink-derived spatial restraints.
AB  - The identification of crosslinks by mass spectrometry has recently been
      established as an integral part of the hybrid structural analysis of protein
      complexes and networks. The crosslinking analysis determines distance restraints
      between two covalently linked amino acids which are typically summarized in a
      table format that precludes the immediate and comprehensive interpretation of the
      topological data. xVis displays crosslinks in clear schematic representations in
      form of a circular, bar or network diagram. The interactive graphs indicate the
      linkage sites and identification scores, depict the spatial proximity of
      structurally and functionally annotated protein regions and the evolutionary
      conservation of amino acids and facilitate clustering of proteins into
      subcomplexes according to the crosslink density. Furthermore, xVis offers two
      options for the qualitative assessment of the crosslink identifications by
      filtering crosslinks according to identification scores or false discovery rates
      and by displaying the corresponding fragment ion spectrum of each crosslink for
      the manual validation of the mass spectrometric data. Our web server provides an
      easy-to-use tool for the fast topological and functional interpretation of
      distance information on protein complex architectures and for the evaluation of
      crosslink fragment ion spectra. xVis is available under a Creative Commons
      Attribution-ShareAlike 4.0 International license at
      http://xvis.genzentrum.lmu.de/. 

PMID- 25956652
TI  - Versatile genetic assembly system (VEGAS) to assemble pathways for expression in
      S. cerevisiae.
AB  - We have developed a method for assembling genetic pathways for expression in
      Saccharomyces cerevisiae. Our pathway assembly method, called VEGAS (Versatile
      genetic assembly system), exploits the native capacity of S. cerevisiae to
      perform homologous recombination and efficiently join sequences with terminal
      homology. In the VEGAS workflow, terminal homology between adjacent pathway genes
      and the assembly vector is encoded by 'VEGAS adapter' (VA) sequences, which are
      orthogonal in sequence with respect to the yeast genome. Prior to pathway
      assembly by VEGAS in S. cerevisiae, each gene is assigned an appropriate pair of
      VAs and assembled using a previously described technique called yeast Golden Gate
      (yGG). Here we describe the application of yGG specifically to building
      transcription units for VEGAS assembly as well as the VEGAS methodology. We
      demonstrate the assembly of four-, five- and six-gene pathways by VEGAS to
      generate S. cerevisiae cells synthesizing beta-carotene and violacein. Moreover,
      we demonstrate the capacity of yGG coupled to VEGAS for combinatorial assembly. 

PMID- 25956654
TI  - ProtPhylo: identification of protein-phenotype and protein-protein functional
      associations via phylogenetic profiling.
AB  - ProtPhylo is a web-based tool to identify proteins that are functionally linked
      to either a phenotype or a protein of interest based on co-evolution. ProtPhylo
      infers functional associations by comparing protein phylogenetic profiles (co
      occurrence patterns of orthology relationships) for more than 9.7 million non
      redundant protein sequences from all three domains of life. Users can query any
      of 2048 fully sequenced organisms, including 1678 bacteria, 255 eukaryotes and
      115 archaea. In addition, they can tailor ProtPhylo to a particular kind of
      biological question by choosing among four main orthology inference methods based
      either on pair-wise sequence comparisons (One-way Best Hits and Best Reciprocal
      Hits) or clustering of orthologous proteins across multiple species (OrthoMCL and
      eggNOG). Next, ProtPhylo ranks phylogenetic neighbors of query proteins or
      phenotypic properties using the Hamming distance as a measure of similarity
      between pairs of phylogenetic profiles. Candidate hits can be easily and flexibly
      prioritized by complementary clues on subcellular localization, known protein
      protein interactions, membrane spanning regions and protein domains. The
      resulting protein list can be quickly exported into a csv text file for further
      analyses. ProtPhylo is freely available at http://www.protphylo.org. 

PMID- 25956655
TI  - Mitochondrial translocation of APE1 relies on the MIA pathway.
AB  - APE1 is a multifunctional protein with a fundamental role in repairing nuclear
      and mitochondrial DNA lesions caused by oxidative and alkylating agents.
      Unfortunately, comprehensions of the mechanisms regulating APE1 intracellular
      trafficking are still fragmentary and contrasting. Recent data demonstrate that
      APE1 interacts with the mitochondrial import and assembly protein Mia40
      suggesting the involvement of a redox-assisted mechanism, dependent on the
      disulfide transfer system, to be responsible of APE1 trafficking into the
      mitochondria. The MIA pathway is an import machinery that uses a redox system for
      cysteine enriched proteins to drive them in this compartment. It is composed by
      two main proteins: Mia40 is the oxidoreductase that catalyzes the formation of
      the disulfide bonds in the substrate, while ALR reoxidizes Mia40 after the
      import. In this study, we demonstrated that: (i) APE1 and Mia40 interact through
      disulfide bond formation; and (ii) Mia40 expression levels directly affect APE1's
      mitochondrial translocation and, consequently, play a role in the maintenance of
      mitochondrial DNA integrity. In summary, our data strongly support the hypothesis
      of a redox-assisted mechanism, dependent on Mia40, in controlling APE1
      translocation into the mitochondrial inner membrane space and thus highlight the
      role of this protein transport pathway in the maintenance of mitochondrial DNA
      stability and cell survival. 

PMID- 25956656
TI  - The relationship between Glasgow Prognostic Score and serum tumor markers in
      patients with advanced non-small cell lung cancer.
AB  - BACKGROUND: Glasgow Prognostic Score (GPS) has been reported as a powerful
      prognostic tool for patients with advanced non-small cell lung cancer (NSCLC).
      The aim of this study was to assess the relationship between GPS and prognosis
      related tumor markers in patients with advanced NSCLC. METHODS: We included 138
      advanced NSCLC patients and twenty healthy controls in the study. GPS was
      calculated by combined serum C-reactive protein (CRP) and albumin. Three serum
      tumor markers, which included cytokeratin 19 fragment antigen 21-1 (CYFRA21-1),
      carcinoembryonic antigen (CEA) and tissue polypeptide specific antigen (TPS),
      were detected by enzyme-linked immunosorbent assay (ELISA). GPS and tumor markers
      were all assessed before chemotherapy. All patients received at least 2 courses
      of cisplatin-based chemotherapy. After that, 2 to 5 years follow-up was
      conducted. RESULTS: Median levels of CYFRA21-1 were 1.5 ng/ml (0.1-3.1 ng/ml) in
      healthy controls, and 4.6 ng/ml (0.7-35.2 ng/ml) in GPS 0 advanced NSCLC, 11.2
      ng/ml (0.4-89.2) ng/ml in GPS 1 advanced NSCLC, and 15.7 ng/ml (2.9-134.6 ng/ml)
      in GPS 2 advanced NSCLC, respectively. Median levels of CYFRA21-1 were higher in
      NSCLC patients than in healthy controls, and CYFRA21-1 increased gradually
      according to GPS category in NSCLC patients (P< 0.05). Similar results were found
      for median levels of CEA and TPS in healthy controls and NSCLC patients (P <
      0.05). In NSCLC patients, positive correlations were found between CYFRA21-1 and
      GPS, CEA and GPS, TPS and GPS. The Spearman's rank correlation coefficient were
      0.67 (P < 0.05), 0.61 (P < 0.05) and 0.55 (P < 0.05), respectively. Survival
      analyses showed GPS was an independent prognostic factor for advanced NSCLC.
      CYFRA21-1(>3.3 ng/ml) and TPS (>80 U/l) were related with the prognosis of
      advanced NSCLC by univariate analyses, but multivariate analyses showed CYFRA21
      1, TPS and CEA were not the independent prognostic factors for advanced NSCLC.
      CONCLUSIONS: Our results showed GPS were positive correlated with CYFRA21-1, CEA
      and TPS in patients with advanced NSCLC. However, GPS was more efficient in
      predicting prognosis of advanced NSCLC than these three single prognosis related
      tumor markers.

PMID- 25956657
TI  - Endoscopic ultrasound findings predict the recurrence of esophageal varices after
      endoscopic band ligation: a prospective cohort study.
AB  - OBJECTIVE: Variceal recurrence following endoscopic band ligation (EBL) is
      common. Esophageal collateral veins (ECV) are observed by endoscopic ultrasound
      (EUS) in patients with portal hypertension. The aim of the present study was to
      assess the role of EUS in predicting the recurrence of esophageal varices
      following EBL. MATERIAL AND METHODS: Forty patients who had undergone EBL for
      eradication of varices were examined over a 12-month period to detect variceal
      recurrence. EUS was performed before ligation to detect and describe the type,
      grade, and the number of ECV. EUS findings obtained prior to EBL were compared in
      the variceal recurrence and non-recurrence groups. RESULTS: Of the 40 patients,
      19 (47.5%) had variceal recurrence within 12 months of EBL. Univariate logistic
      regression analysis showed that severe peri-ECV (p < 0.001), multiple peri-ECV (p
      < 0.001), and the presence of perforating veins (p < 0.014) were statistically
      significantly related to the variceal recurrence after EBL. Multivariate logistic
      regression model found that only severe peri-ECV (odds ratio [OR] = 24.39; 95%
      confidence interval [CI]: 2.34-253.78) and multiple peri-ECV (OR = 24.39; 95% CI:
      2.34-253.78) remained as independent prognostic factors for variceal recurrence.
      The sensitivity and specificity of multivariate logistic regression model in
      predicting variceal recurrence was 89.2% and 90.5%, respectively (prognostic
      value (AUC) = 0.946). CONCLUSION: Recurrence rate of esophageal varices after EBL
      is high (47.5%). EUS can clearly depict ECV and has a value in predicting
      variceal recurrence after EBL; severe peri-ECV and multiple peri-ECV were
      significant and independent prognostic factors associated with variceal
      recurrence risk.

PMID- 25956658
TI  - The role of the dermatologist in detecting elder abuse and neglect.
AB  - The National Research Council of the National Academies defines elder
      mistreatment as: (1) intentional actions that cause harm or create serious risk
      of harm (whether or not harm is intended) to a vulnerable elder by a caregiver or
      other person who stands in a trust relationship to the elder; or (2) failure by a
      caregiver to satisfy the elder's basic needs or to protect the elder from harm.
      Estimates of the prevalence of elder abuse have ranged from 2.2% to 18.4%.
      Dermatologists are uniquely positioned to identify and manage suspected cases of
      elder abuse given their expertise in distinguishing skin lesions of abuse from
      organic medical disease and their patient populations with strong elderly
      representation. This article discusses aspects of both the screening and
      management of elder abuse with particular relevance to dermatologists. Like
      physicians across medical specialties, dermatologists must be familiar with those
      aspects of elder abuse in screening, diagnosis, management, and reporting that
      are unique to their field and to those aspects that are applicable to all health
      care providers. 

PMID- 25956659
TI  - Systemic granulocyte colony-stimulating factor (G-CSF) enhances wound healing in
      dystrophic epidermolysis bullosa (DEB): Results of a pilot trial.
AB  - BACKGROUND: Chronic nonhealing wounds are the norm in patients with inherited
      epidermolysis bullosa (EB), especially those with dystrophic EB (DEB). A possible
      benefit in wound healing after subcutaneous treatment with granulocyte colony
      stimulating factor (G-CSF) was suggested from an anecdotal report of a patient
      given this during stem cell mobilization before bone-marrow transplantation.
      OBJECTIVE: We sought to determine whether benefit in wound healing in DEB skin
      might result after 6 daily doses of G-CSF and to confirm its safety. METHODS:
      Patients were assessed for changes in total body blister and erosion counts,
      surface areas of selected wounds, and specific symptomatology after treatment.
      RESULTS: Seven patients with DEB (recessive, 6; dominant, 1) were treated daily
      with subcutaneous G-CSF (10 MUg/kg/dose) and reevaluated on day 7. For all
      patients combined, median reductions of 75.5% in lesional size and 36.6% in
      blister/erosion counts were observed. When only the 6 responders were considered,
      there were median reductions of 77.4% and 38.8% of each of these measured
      parameters, respectively. No adverse side effects were noted. LIMITATIONS:
      Limitations include small patient number, more than 1 DEB subtype included, and
      lack of untreated age-matched control subjects. CONCLUSIONS: Subcutaneous G-CSF
      may be beneficial in promoting wound healing in some patients with DEB when
      conventional therapies fail.

PMID- 25956660
TI  - Combination therapy with 308-nm excimer laser, topical tacrolimus, and short-term
      systemic corticosteroids for segmental vitiligo: A retrospective study of 159
      patients.
AB  - BACKGROUND: Segmental vitiligo (SV) is characterized by a unilateral and
      localized distribution, early onset, and stable disease after rapid progression.
      And SV is often associated with poor response to various treatment modalities.
      OBJECTIVE: We sought to evaluate the effectiveness of combination therapy with
      308-nm excimer laser, topical tacrolimus, and short-term systemic corticosteroids
      for SV, and to search for factors associated with the treatment response.
      METHODS: A retrospective interventional case-series study was performed on 159
      patients with SV who were treated with the combination therapy for more than 3
      months. RESULTS: The rate of 75% or more repigmentation was 50.3% after a median
      treatment duration of 12.1 months; 36.5% and 13.8% of the patients showed nearly
      complete (75%-99%) and complete (100%) repigmentation, respectively.
      Multivariable analysis showed the following to be independent factors with poor
      response: disease duration longer than 12 months (odds ratio 0.372, 95%
      confidence interval 0.157-0.882, P = .025), poliosis (odds ratio 0.494, 95%
      confidence interval 0.247-0.988, P = .046), and plurisegmental subtype (odds
      ratio 0.175, 95% confidence interval 0.065-0.474, P = .001). LIMITATIONS: This
      was a retrospective study. CONCLUSION: The combination therapy is effective for
      SV. Prolonged disease duration, poliosis, and plurisegmental subtype were shown
      to be independent prognostic factors of poor response in patients with SV.

PMID- 25956661
TI  - Efficacy and safety of tavaborole topical solution, 5%, a novel boron-based
      antifungal agent, for the treatment of toenail onychomycosis: Results from 2
      randomized phase-III studies.
AB  - BACKGROUND: Onychomycosis, a fungal nail infection, can impact quality of life.
      OBJECTIVE: We sought to evaluate the efficacy and safety of tavaborole topical
      solution, 5% for treatment of toenail onychomycosis. METHODS: In 2 phase-III
      trials, adults with distal subungual onychomycosis affecting 20% to 60% of a
      target great toenail were randomized 2:1 to tavaborole or vehicle once daily for
      48 weeks. The primary end point was complete cure of the target great toenail
      (completely clear nail with negative mycology) at week 52. Secondary end points
      included completely or almost clear nail, negative mycology, completely or almost
      clear nail plus negative mycology, and safety. RESULTS: Rates of negative
      mycology (31.1%-35.9% vs 7.2%-12.2%) and complete cure (6.5% and 9.1% vs 0.5% and
      1.5%) significantly favored tavaborole versus vehicle (P <= .001). Completely or
      almost clear nail rates also significantly favored tavaborole versus vehicle
      (26.1%-27.5% vs 9.3%-14.6%; P < .001). Rates of completely or almost clear nail
      plus negative mycology (15.3%-17.9% vs 1.5%-3.9%) were significantly greater for
      tavaborole versus vehicle (P < .001). Application-site reactions with tavaborole
      included exfoliation (2.7%), erythema (1.6%), and dermatitis (1.3%). LIMITATIONS:
      Duration of follow-up is a limitation. CONCLUSION: Tavaborole demonstrates a
      favorable benefit-risk profile in treatment of toenail onychomycosis.

PMID- 25956663
TI  - Hospital practice explains variation in outcomes in extremely premature infants,
      US study finds.

PMID- 25956662
TI  - Allergenicity characteristics of germinated soybean proteins in a BALB/c mouse
      model.
AB  - Soybean proteins are widely used in many food products. However they also
      commonly cause food allergy. This study aimed to characterize the allergenicity
      of germinated soybean proteins in a BALB/c mouse model. Mice were orally
      sensitized with germinated soybean proteins or soybean proteins using cholera
      toxin as adjuvant. Anaphylactic shock reactions as well as changes in body
      temperature, specific antibody levels, mast cell protease-1 (mMCP-1)
      concentrations, morphological structure of duodenum, and cytokines were
      determined after the mice were challenged with germinated soybean proteins or
      soybean proteins. In contrast to soybean proteins, oral sensitization to
      germinated soybean proteins did not result in anaphylactic shock symptoms or
      decreased body temperature in mice. However, a minor damage of the intestinal
      villus existed after the challenge. A tendency toward decreased allergen-specific
      IgE, IgG and IgG1 levels, and mMCP-1 concentration was observed, accompanied by a
      repression of IL-4, IL-5, IL-13 and IFN-gamma production in spleen cell cultures.
      Results indicate that germinated soybean proteins did not provoke remarkable
      allergic reactions compared to soybean proteins. Germinated soybean proteins have
      the potential to be a safe dietary formula for humans at risk of soybean allergy.
      However, additional studies on the underlying mechanisms and clinical trials are
      necessary. 

PMID- 25956664
TI  - Intracranial involvement by multiple myeloma.
AB  - Intracranial involvement is a rare complication of multiple myeloma. It results
      either from direct extra-osseous spread from adjacent skeletal plasmacytomas or
      extra-medullary disease via haematogenous dissemination. The imaging appearances
      are non-specific, and dural, leptomeningeal, and parenchymal involvement can all
      occur. The purpose of this review is to illustrate the various neuroimaging
      appearances of this rare entity, focusing on MRI. 

PMID- 25956665
TI  - Diagnostic yield and impact of MRI for acute ischaemic stroke in patients
      presenting with dizziness and vertigo.
AB  - AIM: To identify predictors of acute ischaemic stroke (AIS) and evaluate the
      diagnostic yield and impact of magnetic resonance imaging (MRI) in patients
      imaged for dizziness and vertigo. MATERIALS AND METHODS: Patients imaged using
      MRI, including diffusion-weighted imaging (DWI) with or without computed
      tomography (CT), for dizziness and vertigo over a 2-year period were identified
      retrospectively. MRI findings were categorised as "acute ischaemic stroke",
      "significant", or "non-significant". We reviewed the medical records to identify
      presenting symptoms and signs, vascular risk factors, duration of symptoms, and
      pre- and post-MRI clinical management in patients with proven stroke. RESULTS:
      One hundred and eighty-eight patients were included: 39 with vertebrobasilar AIS
      (20.7%), 32 (17%) with a significant but non-ischaemic abnormality, and 117
      (62.2%) with a normal or non-related abnormality. The sensitivity of CT in
      diagnosing AIS was 9.52% (95% CI: 1.67-31.8%). Posterior inferior cerebellar
      artery (PICA) territory infarcts were the most common (38.5%). Patients with AIS
      were significantly more likely to be older than 50 years (p = 0.04), have a
      greater number of cardiovascular risk factors (p < 0.01), shorter duration of
      symptoms (p = 0.03), and at least one neurological sign (p = 0.02). DWI MRI had a
      diagnostic impact on 21.6% patients with stroke. CONCLUSION: MRI plays an
      important role in differentiating peripheral and central aetiology when this
      proves challenging clinically. Predictors of AIS were identified that aid patient
      selection for MRI, to increase the yield and impact of neuroimaging.

PMID- 25956667
TI  - Case study of Brugada syndrome presenting initially as acute myocardial
      infarction.

PMID- 25956666
TI  - Models for treating depression in specialty medical settings: a narrative review.
AB  - OBJECTIVE: This review answered two questions: (a) what types of specialty
      medical settings are implementing models for treating depression, and (b) do
      models for treating depression in specialty medical settings effectively treat
      depression symptoms? METHOD: We searched Medline/Pubmed to identify articles,
      published between January 1990 and May 2013, reporting on models for treating
      depression in specialty medical settings. Included studies had to have adult
      participants with comorbid medical conditions recruited from outpatient,
      nonstandard primary care settings. Studies also had to report specific, validated
      depression measures. RESULTS: Search methods identified nine studies (six
      randomized controlled trials, one nonrandomized controlled trial and two
      uncontrolled trials), all representing integrated care for depression, in three
      specialty settings (oncology, infectious disease, neurology). Most studies (N=7)
      reported greater reductions in depression among patients receiving integrated
      care compared to usual care, particularly in oncology clinics. CONCLUSIONS:
      Integrated care for depression in specialty medical settings can improve
      depression outcomes. Additional research is needed to understand the
      effectiveness of incorporating behavioral and/or psychological treatments into
      existing methods. When developing or selecting a model for treating depression in
      specialty medical settings, clinicians and researchers will benefit from choosing
      specific components and measures most relevant to their target populations.

PMID- 25956668
TI  - Fascia Iliaca (FICB) block in the emergency department for adults with neck of
      femur fractures: A review of the literature.
AB  - OBJECTIVE: To ascertain the efficacy of fascia iliaca block for providing
      analgesia for adults with proximal femoral fractures when compared with standard
      management. The potential for non-medical practitioners to deliver this block was
      also assessed. METHOD: Medline and CINAHL were searched, as were the reference
      lists from located articles. The title was reviewed and eligibility determined by
      this and abstract. The full text was then reviewed. A wide range of papers were
      included. The Cochrane library was also searched as were case reports. RESULTS:
      179 papers were identified, of which 12 were included for review after
      eligibility sorting and removal of duplicates. These comprised 2 randomised
      control trials, an audit, a literature review, 5 cohort studies, NICE guidelines
      and an interventional uncontrolled trial. The Cochrane library revealed no
      studies that met the search criteria. 2 case reports detailing adverse outcomes
      were identified. All papers showed FICB to have a similar or greater efficacy to
      systemic treatment, with fewer adverse side effects. CONCLUSIONS: FICB is an
      effective method of providing analgesia in these patients without the undesirable
      side effects of systemic opioids. Non- medical practitioners are capable of
      administering this block.

PMID- 25956669
TI  - Clinician enteral feeding preferences for very preterm babies in the UK.

PMID- 25956670
TI  - Prenatal therapy in transient abnormal myelopoiesis: a systematic review.
AB  - OBJECTIVE: To systematically review current evidence regarding prenatal diagnosis
      and management of transient abnormal myelopoiesis (TAM) in fetuses with trisomy
      21. A novel case of GATA1-positive TAM, in which following serial in utero blood
      transfusion clinical improvement and postnatal remission were observed, is
      included. SEARCH STRATEGY AND DATA COLLECTION: A systematic search of electronic
      databases (inception to October 2014) and reference lists, hand-searching of
      journals and expert contact. All confirmed cases of prenatal TAM were included
      for analysis. Data on study characteristics, design and quality were obtained.
      RESULTS: Of 73 potentially relevant citations identified, 22 studies were
      included, describing 39 fetuses. All studies included comprised single case or
      small cohort studies; overall quality was 'very low'. Fetal/neonatal outcome was
      poor; 12 stillbirths (30.8%), 4 neonatal deaths (10.2%) and 7 infant deaths
      (17.9%). In two cases, the pregnancy was terminated (5.1%). TAM was primarily
      detected in the third trimester (79.4%), and in 14 a retrospective diagnosis was
      made postpartum. Ultrasound features indicative of TAM included hepatomegaly+/
      splenomegaly (79.5%), hydrops fetalis (30.8%), pericardial effusion (23.1%) and
      aberrant liquor volume (15.4%). When performed, liver function tests were
      abnormal in 91.6% of cases. CONCLUSIONS: Prenatal TAM presents a challenging
      diagnosis, and prognosis is poor, with consistently high mortality. A low
      threshold to measure haematological and biochemical markers is advised when
      clinical features typical of TAM are detected in the context of trisomy 21.
      Larger prospective studies are warranted to accurately ascertain the role of
      GATA1 analysis and potential value of prenatal therapy.

PMID- 25956671
TI  - High-risk HPV detection and genotyping by APTIMA HPV using cervical samples.
AB  - High-risk human papillomavirus (HPV) detection and genotyping is critical for
      cervical cancer screening. Testing of 967 cervical cytology specimens in
      PreservCyt preservative revealed similar positivity rates for HC2 (13.8%) and
      APTIMA HPV (AHPV) tests (13.5%, p=0.89) and high overall agreement (94.6%,
      kappa=0.77). A trend towards higher HPV16 positivity rates by the Cobas HPV test
      (23.0%, 26/113) compared to the AHPV genotyping assay (19.5%, 22/113; p=0.125)
      was noted. No cross-contamination was detected with AHPV in a challenge
      experiment. 

PMID- 25956672
TI  - Detection and absolute quantitation of Tomato torrado virus (ToTV) by real time
      RT-PCR.
AB  - Tomato torrado virus (ToTV) causes serious damage to the tomato industry and
      significant economic losses. A quantitative real-time reverse-transcription
      polymerase chain reaction (RT-qPCR) method using primers and a specific
      TaqMan((r)) MGB probe for ToTV was developed for sensitive detection and
      quantitation of different ToTV isolates. A standard curve using RNA transcripts
      enabled absolute quantitation, with a dynamic range from 10(4) to 10(10) ToTV RNA
      copies/ng of total RNA. The specificity of the RT-qPCR was tested with twenty
      three ToTV isolates from tomato (Solanum lycopersicum L.), and black nightshade
      (Solanum nigrum L.) collected in Spain, Australia, Hungary and France, which
      covered the genetic variation range of this virus. This new RT-qPCR assay enables
      a reproducible, sensitive and specific detection and quantitation of ToTV, which
      can be a valuable tool in disease management programs and epidemiological
      studies. 

PMID- 25956673
TI  - In vitro leishmanicidal activity of 1,3-disubstituted 5-nitroindazoles.
AB  - The antiprotozoal activity of some indazole-derived amines (2, 3, 5-8) as well as
      that of some simple structurally related 3-alkoxy-1-alkyl-5-nitroindazoles (1, 4)
      against promastigote and amastigote forms of Leishmania infantum and Leishmania
      braziliensis is reported. In some cases, these compounds showed in vitro
      activities against the different morphological forms of Leishmania similar to or
      higher than those of the reference drug glucantime; this fact, along with low
      unspecific cytotoxicities against macrophages shown by some of them, led to good
      selectivity indexes (SI). The high efficiency of some 5-nitroindazoles against
      the mentioned protozoa was confirmed by further in vitro studies on infection
      rates. Complementary analyses by (1)H NMR of the changes on the metabolites
      excreted by parasites after treatment with the more active indazole derivatives
      in many cases showed the decreased excretion of succinate and increased levels of
      acetate, lactate and alanine, as well as, in some cases, the appearance of
      glycine and pyruvate as new metabolites. Damage caused by indazoles at the
      glycosomal or mitochondrial level are consistent with these metabolic changes as
      well as with the huge ultrastructural alterations observed by transmission
      electron microscopy (TEM), especially affecting the mitochondria and other
      cytoplasmic organelles. 

PMID- 25956674
TI  - Cigarette smoking and risk of hip fracture in women: a meta-analysis of
      prospective cohort studies.
AB  - BACKGROUND AND OBJECTIVES: Whether cigarette smoking can increase the risk of hip
      fracture in women is unclear. This meta-analysis, which pooled results from 10
      prospective cohort studies, was performed to derive a more precise estimation
      between cigarette smoking and the risk of hip fracture in women. MATERIALS AND
      METHODS: Pubmed, Cochrane Central Register of Controlled Trials and ISI Web of
      Science were systematically searched to identify relevant studies. A meta
      analysis was performed to examine the association among 10 studies. The pooled
      risk estimates were calculated by using both random- and fixed-effects model.
      Heterogeneity among articles and their publications bias were also tested. All of
      the statistical analyses were performed using the software programs STATA
      (version 12.0). RESULTS: Relative risk was significantly increased in current
      female smokers (pooled RR, 1.30; 95%CI, 1.16-1.45). The association was
      significant among the high-dose smokers (more than 15 cigarettes per day) while
      not among the low-does smokers (less than 15 cigarettes per day). Omission of any
      single study had little effect on the pooled risk estimate. Former smokers had a
      similar RR of hip fracture (RR, 1.02; 95%CI, 0.93-1.11) to published papers.
      Smoking cessation for >=10 years leads to a significant decline in risk.
      CONCLUSIONS: Smoking is associated with an increased hip fracture risk in women.
      Cessation of smoking for >=10 years had a decreased impact on risk of hip
      fracture. Given the inconsistency among the studies in the choice of adjustments,
      the associations between cigarette smoking and risk of hip fracture in women
      await further investigation.

PMID- 25956675
TI  - Finding new sources from "using different plants as the same herb": A case study
      of Huang-lian in Northwest Yunnan, China.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Traditional and local medicinal knowledge would
      be useful for finding pharmaceutical resources. Ethnopharmacological methods,
      especially quantitative analysis could help us to pre-screen herbs in field
      studies. "Using different plants as the same herb" is common in both traditional
      and local medicinal systems in China. In terms of medicine safety, it is not best
      choice, for it would lead to difficulty in controlling the quality, safety and
      efficacy of herbs. However, from the perspective of finding new resources for
      pharmaceutical industry, it would be beneficial. The usage of Huang-lian is one
      of the typical examples of "using different plants as the same herb". According
      to the previous Phytochemical and Pharmacological studies, berberine is the
      common effective compound of most of the species used as Huang-lian. Recently,
      berberine and other effective compounds of Huang-lian have gained much more
      attention and will become more popular in both medicinal researches and
      pharmaceutical industry. In our preliminary field work, we found that dozens of
      plant species might be used as Huang-lian by local people in Northwest Yunnan, an
      area well known by its rich biodiversity and culture diversity. These herbs might
      have potential value for pharmaceutical industry, for example, it could be used
      as the new resources to extract berberine and other effective compounds. Due to
      this, it is very necessary to collect, identify, document, and analyze the herbs
      used as Huang-lian in NW Yunnan. In the present study, we focused on that how to
      use traditional and local medicinal knowledge to find resources for
      pharmaceutical industry. MATERIAL AND METHODS: In the field work, interviews and
      participative observation were used. In the quantitative analysis of the local
      knowledge, Informant consensus factor (Fic), Use value (UV) and Relative
      frequency of citation (RFC) were used. RESULTS AND DISCUSSION: A total of 230 key
      informants were interviewed and 29 plant species belonging to 8 families and 11
      genera used as Huang-lian were collected in the study area. Diarrhoea had the
      highest value of Fic.xiana had the highest value of UV and RFC. The main
      effective compounds of most of these species were related to the protoberberine
      group of isoquinoline alkaloids, e.g. berberine, jatrorrhizin and palmatine,
      according to the previous phytochemical studies. CONCLUSION: The range of sources
      of Huang-lian were very wide in NW Yunnan. Treating diarrhoea was the most common
      use of these species, most of which contained berberine. Based on the results of
      quantitative analysis, M. duclouxiana may had the greatest potential to future
      uses, e.g. as a resource for pharmaceutical industry. In the present study, we
      did not discuss whether the herbs used as Huang-lian could replace the standard
      Huang-lian in traditional or local medicine or not, and we just wanted to explore
      how this phenomenon could be used to find new resources for pharmaceutical
      industry.

PMID- 25956676
TI  - Liver enzyme abnormalities in taking traditional herbal medicine in Korea: A
      retrospective large sample cohort study of musculoskeletal disorder patients.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The objective of this study is to report the
      incidence of liver injury from herbal medicine in musculoskeletal disease
      patients as large-scale studies are scarce. Considering that herbal medicine is
      frequently used in patients irrespective of liver function in Korea, we
      investigated the prevalence of liver injury by liver function test results in
      musculoskeletal disease patients. MATERIALS AND METHODS: Of 32675 inpatients
      taking herbal medicine at 7 locations of a Korean medicine hospital between 2005
      and 2013, we screened for liver injury in 6894 patients with liver function tests
      (LFTs) at admission and discharge. LFTs included t-bilirubin, AST, ALT, and ALP.
      Liver injury at discharge was assessed by LFT result classifications at admission
      (liver injury, liver function abnormality, and normal liver function). In
      analyses for risk factors of liver injury at discharge, we adjusted for age, sex,
      length of stay, conventional medicine intake, HBs antigen/antibody, and liver
      function at admission. RESULTS: A total 354 patients (prevalence 5.1%) had liver
      injury at admission, and 217 (3.1%) at discharge. Of the 354 patients with liver
      injury at admission, only 9 showed a clinically significant increase after herbal
      medicine intake, and 225 returned to within normal range or showed significant
      liver function recovery. Out of 4769 patients with normal liver function at
      admission, 27 (0.6%) had liver injury at discharge. In multivariate analyses for
      risk factors, younger age, liver function abnormality at admission, and HBs
      antigen positive were associated with injury at discharge. CONCLUSIONS: The
      prevalence of liver injury in patients with normal liver function taking herbal
      medicine for musculoskeletal disease was low, and herbal medicine did not
      exacerbate liver injury in most patients with injury prior to intake.

PMID- 25956677
TI  - The role of visual saliency for the allocation of attention: Evidence from
      spatial neglect and hemianopia.
AB  - Visual scanning and exploration of natural scenes not only depends on specific
      objects, but also on local features. Models of spatial attention propose that
      features such as orientation or colour are processed pre-attentively and in
      parallel. According to these models attention interferes at a later stage, where
      features are combined into a representation of visual saliency. Saliency is a
      good predictor of ocular fixations during scanning of static pictures. Here, we
      tested whether fixations of patients with left spatial neglect, hemianopia, or
      both can be predicted based on local image content. Participants were asked to
      freely scan natural images while saccades and ocular fixations were registered.
      Hemianopic patients produced a similar distribution of fixations and relied
      similarly on picture saliency as healthy controls. In contrast, neglect patients
      looked to image regions with increased saliency and higher local orientation and
      intensity thresholds on the neglected side of space. The reliance on increased
      saliency during visual exploration was predicted by damage to subcortical regions
      interconnecting the inferior parietal and lateral premotor cortex. These findings
      suggest that spatial neglect leads to a combined attentive and pre-attentive
      deficit in the processing of saliency and feature information. 

PMID- 25956678
TI  - Development of a Novel Phosphorylated AMPK Protection Assay for High-Throughput
      Screening Using TR-FRET Assay.
AB  - AMP-activated protein kinase (AMPK), a conserved heterotrimeric kinase, serves as
      an energy sensor maintaining energy balance at both cellular and whole-body
      levels and plays multiple beneficial roles in carbohydrate and lipid metabolism,
      which makes AMPK an attractive target for diabetes and other metabolic disorders.
      To date, establishment of the physiologically relevant biochemical assay for AMPK
      has not been reported. Here we developed a phosphorylated AMPK protection assay
      based on a time-resolved fluorescence resonance energy transfer (TR-FRET) assay,
      using the protein phosphatase 2A (PP2A) to dephosphorylate AMPK. The partially
      dephosphorylated AMPK by PP2A had lower activity than phosphorylated AMPK. This
      specific TR-FRET assay for AMPK was optimized in the 384-well format and produced
      similar EC(50) values for AMPK activators AMP and A769662 and a similar IC(50)
      value for AMPK inhibitor compound C, as previously reported. Under the optimized
      conditions, the assay Z' factor calculated over 160 data points has an optimal
      value greater than 0.5, which is suitable for high-throughput screening. In
      conclusion, this phosphorylated AMPK protection assay we developed is very
      robust, sensitive, and simple to perform and may be useful as a high-throughput
      assay for identifying AMPK activators with the ability of preventing activated
      AMPK against dephosphorylation by phosphatase in the physiological conditions.

PMID- 25956679
TI  - Inosine and hypoxanthine as novel biomarkers for cardiac ischemia: from bench to
      point-of-care.
AB  - Cardiac ischemia associated with acute coronary syndrome and myocardial
      infarction is a leading cause of mortality and morbidity in the world. A rapid
      detection of the ischemic events is critically important for achieving timely
      diagnosis, treatment and improving the patient's survival and functional
      recovery. This minireview provides an overview on the current biomarker research
      for detection of acute cardiac ischemia. We primarily focus on inosine and
      hypoxanthine, two by-products of ATP catabolism. Based on our published findings
      of elevated plasma concentrations of inosine/hypoxanthine in animal laboratory
      and clinical settings, since 2006 we have originally proposed that these two
      purine molecules can be used as rapid and sensitive biomarkers for acute cardiac
      ischemia at its very early onset (within 15 min), hours prior to the release of
      heart tissue necrosis biomarkers such as cardiac troponins. We further developed
      a chemiluminescence technology, one of the most affordable and sensitive
      analytical techniques, and we were able to reproducibly quantify and
      differentiate total hypoxanthine concentrations in the plasma samples from
      healthy individuals versus patients suffering from ischemic heart disease.
      Additional rigorous clinical studies are needed to validate the plasma
      inosine/hypoxanthine concentrations, in conjunction with other current cardiac
      biomarkers, for a better revelation of their diagnostic potentials for early
      detection of acute cardiac ischemia.

PMID- 25956680
TI  - Biliary and duodenal drainage for reducing the radiotoxic risk of antineoplastic
      131I-hypericin in rat models.
AB  - Necrosis targeting radiopharmaceutical (131)I-hypericin ((131)I-Hyp) has been
      studied for the therapy of solid malignancies. However, serious side effects may
      be caused by its unwanted radioactivity after being metabolized by the liver and
      excreted via bile in the digestive tract. Thus the aim of this study was to
      investigate two kinds of bile draining for reducing them. Thirty-eight normal
      rats were intravenously injected with (131)I-Hyp, 24 of which were subjected to
      the common bile duct (CBD) drainage for gamma counting of collected bile and
      tissues during 1-6, 7-12, 13-18, and 19-24 h (n = 6 each group), 12 of which were
      divided into two groups (n = 6 each group) for comparison of the drainage
      efficiency between CBD catheterization and duodenum intubation by collecting
      their bile at the first 4 h. Afterwards the 12 rats together with the last two
      rats which were not drained were scanned via single-photon emission computerized
      tomography/computed tomography (SPECT/CT) to check the differences. The images
      showed that almost no intestinal radioactivity can be found in those 12 drained
      rats while discernible radioactivity in the two undrained rats. The results also
      indicated that the most of the radioactivity was excreted from the bile within
      the first 12 h, accounting to 92% within 24 h. The radioactive metabolites in the
      small and large intestines peaked at 12 h and 18 h, respectively. No differences
      were found in those two ways of drainages. Thus bile drainage is highly
      recommended for the patients who were treated by (131)I-Hyp if human being and
      rats have a similar excretion pattern. This strategy can be clinically achieved
      by using a nasobiliary or nasoduodenal drainage catheter. 

PMID- 25956681
TI  - Budesonide inhalation ameliorates endotoxin-induced lung injury in rabbits.
AB  - Acute respiratory distress syndrome (ARDS) is a serious clinical problem that has
      a 30-50% mortality rate. Budesonide has been used to reduce lung injury. This
      study aims to investigate the effects of nebulized budesonide on endotoxin
      induced ARDS in a rabbit model. Twenty-four rabbits were randomized into three
      groups. Rabbits in the control and budesonide groups were injected with
      endotoxin. Thereafter, budesonide or saline was instilled, ventilated for four
      hours, and recovered spontaneous respiratory. Peak pressure, compliance, and
      PaO2/FiO2 were monitored for 4 h. After seven days, PaO2/FiO2 ratios were
      measured. Wet-to-dry weight ratios, total protein, neutrophil elastase, white
      blood cells, and percentage of neutrophils in BALF were evaluated. TNF-alpha, IL
      1beta, IL-8, and IL-10 in BALF were detected. Lung histopathologic injury and
      seven-day survival rate of the three groups were recorded. Peak pressure was
      downregulated, but compliance and PaO2/FiO2 were upregulated by budesonide.
      PaO2/FiO2 ratios significantly increased due to budesonide. Wet-to-dry weight
      ratios, total protein, neutrophil elastase, white blood cells and percentage of
      neutrophils in BALF decreased in the budesonide group. TNF-alpha, IL-1beta, and
      IL-8 levels decreased in BALF, while IL-10 levels increased in the budesonide
      group. Lung injuries were reduced and survival rate was upregulated by
      budesonide. Budesonide effectively ameliorated respiratory function, attenuated
      endotoxin-induced lung injury, and improved the seven-day survival rate. 

PMID- 25956682
TI  - Utilization of TALEN and CRISPR/Cas9 technologies for gene targeting and
      modification.
AB  - The capability to modify the genome precisely and efficiently offers an extremely
      useful tool for biomedical research. Recent developments in genome editing
      technologies such as transcription activator-like effector nuclease and the
      clustered regularly interspaced short palindromic repeats system have made genome
      modification available for a number of organisms with relative ease. Here, we
      introduce these genome editing techniques, compare and contrast each technical
      approach and discuss their potential to study the underlying mechanisms of human
      disease using patient-derived induced pluripotent stem cells. 

PMID- 25956683
TI  - Wnt5a attenuates hypoxia-induced pulmonary arteriolar remodeling and right
      ventricular hypertrophy in mice.
AB  - Hypoxic pulmonary hypertension (HPH), which is characterized by pulmonary
      arteriolar remodeling and right ventricular hypertrophy, is still a life
      threatening disease with the current treatment strategies. The underlying
      molecular mechanisms of HPH remain unclear. Our previously published study showed
      that Wnt5a, one of the ligands in the Wnt family, was critically involved in the
      inhibition of hypoxia-induced pulmonary arterial smooth muscle cell proliferation
      by downregulation of beta-catenin/cyclin D1 in vitro. In this study, we
      investigated the possible functions and mechanisms of Wnt5a in HPH in vivo.
      Recombinant mouse Wnt5a (rmWnt5a) or phosphate buffered saline (PBS) was
      administered to male C57/BL6 mice weekly from the first day to the end of the two
      or four weeks after exposed to hypoxia (10% O2). Hypoxia-induced pulmonary
      hypertension was associated with a marked increase in beta-catenin/cyclin D1
      expression in lungs. Right ventricular systolic pressure and right ventricular
      hypertrophy index were reduced in animals treated with rmWnt5a compared with PBS.
      Histology showed less pulmonary vascular remodeling and right ventricular
      hypertrophy in the group treated with rmWnt5a than with PBS. Treatment with
      rmWnt5a resulted in a concomitant reduction in beta-catenin/cyclin D1 levels in
      lungs. These data demonstrate that Wnt5a exerts its beneficial effects on HPH by
      regulating pulmonary vascular remodeling and right ventricular hypertrophy in a
      manner that is associated with reduction in beta-catenin/cyclin D1 signaling. A
      therapy targeting the beta-catenin/cyclin D1 signaling pathway might be a
      potential strategy for HPH treatment. 

PMID- 25956684
TI  - Advanced glycation end-products and insulin signaling in granulosa cells.
AB  - Advanced glycation end-products (AGEs) may interfere with insulin intracellular
      signaling and glucose transport in human granulosa cells, potentially affecting
      ovarian function, follicular growth, linked with diminished fertility. The
      potential interaction of AGEs with insulin signaling pathways and glucose
      transport was investigated in human granulosa KGN cells. KGN cells were cultured
      with variable concentrations of human glycated albumin (HGA, 50-200 ug/mL) or
      insulin (100 ng/mL). Combined treatments of KGN cells with insulin (100 ng/mL)
      and HGA (200 ug/mL) were also performed. p-AKT levels and glucose transporter
      type 4 (Glut-4) translocation analysis were performed by Western blot.
      Phosphatidylinositol-3-kinase (PI3K)-specific signaling was checked by using the
      PI3K-inhibitor, LY294002. p-AKT levels were significantly increased following
      insulin treatment compared to basal levels or HGA exposure. This insulin-mediated
      AKT-phosphorylation was PI3K-specific and it was inhibited after combined
      treatment of insulin and HGA. Furthermore, Glut-4 translocation from the
      cytoplasm to the membrane compartments of KGN cells was remarkably reduced after
      the combined treatment of insulin and HGA. The present findings support that AGEs
      interfere with insulin signaling in granulosa cells and prevent Glut-4 membrane
      translocation suggesting that intra ovarian AGEs accumulation, from endogenous or
      exogenous sources, may contribute to the pathophysiology of states characterized
      with anovulation and insulin resistance such as polycystic ovary syndrome.

PMID- 25956685
TI  - Interleukin-10 gene-carrying bifidobacteria ameliorate murine ulcerative colitis
      by regulating regulatory T cell/T helper 17 cell pathway.
AB  - Ulcerative colitis (UC) is a chronic inflammatory bowel disease suggested to be
      closely related to the imbalance of regulatory T cell/T helper 17 cell
      (Treg/Th17) signaling. Previously, we constructed an interleukin-10 (IL-10)
      expression vector, BL-hIL-10, and proved that it ameliorates dextran sulfate
      sodium-induced intestinal inflammation in mice. In this study, we further
      explored the mechanisms underlying BL-hIL-10 treatment from the Treg/Th17
      imbalance perspective. Our results showed that the oral administration of BL-hIL
      10 reduced the UC inflammation in mice significantly, which was assessed by
      disease activity index, spleen index, and pathological changes in colon tissue.
      Moreover, the mice after BL-hIL-10 treatment had increased proportion of Treg
      cells while Th17 cells decreased greatly, leading to the reconstruction of
      Treg/Th17 balance. Furthermore, the Th17 cell-secreted factors, such as IL-6, IL
      17, and IL-23, were reduced, but the Treg-related factors, IL-10 and Transforming
      growth factor-beta1 (TGF-beta1), were elevated accordingly. Finally, Western blot
      confirmed the inhibition of nuclear hypoxia-inducible factor-1alpha (HIF-1alpha)
      and cytoplasmic mechanistic target of rapamycin (mTOR) and signal transducer and
      activator of transcription 3 (STAT3) in intestinal tissues. In conclusion, oral
      administration of BL-hIL-10 can alleviate the inflammation responses of UC in
      murine model through the restoration of Treg/Th17 imbalance, which might be at
      least partially due to the inhibition of hypoxia-mTOR-HIF-1alpha-Th17 axis as
      well as IL-6-STAT3-HIF-1alpha-Th17 pathway. 

PMID- 25956687
TI  - The validity of the GENEActiv wrist-worn accelerometer for measuring adult
      sedentary time in free living.
AB  - OBJECTIVES: Based on self-reported measures, sedentary time has been associated
      with chronic disease and mortality. This study examined the validity of the wrist
      worn GENEactiv accelerometer for measuring sedentary time (i.e. sitting and
      lying) by posture classification, during waking hours in free living adults.
      DESIGN: Fifty-seven participants (age=18-55 years 52% male) were recruited using
      convenience sampling from a large metropolitan Australian university. METHODS:
      Participants wore a GENEActiv accelerometer on their non-dominant wrist and an
      activPAL device attached to their right thigh for 24-h (00:00 to 23:59:59).
      Pearson's Correlation Coefficient was used to examine the convergent validity of
      the GENEActiv and the activPAL for estimating total sedentary time during waking
      hours. Agreement was illustrated using Bland and Altman plots, and intra
      individual agreement for posture was assessed with the Kappa statistic. RESULTS:
      Estimates of average total sedentary time over 24-h were 623 (SD 103) min/day
      from the GENEActiv, and 626 (SD 123) min/day from the activPAL, with an
      Intraclass Correlation Coefficient of 0.80 (95% confidence intervals 0.68-0.88).
      Bland and Altman plots showed slight underestimation of mean total sedentary time
      for GENEActiv relative to activPAL (mean difference: -3.44min/day), with moderate
      limits of agreement (-144 to 137min/day). Mean Kappa for posture was 0.53 (SD
      0.12), indicating moderate agreement for this sample at the individual level.
      CONCLUSIONS: The estimation of sedentary time by posture classification of the
      wrist-worn GENEActiv accelerometer was comparable to the activPAL. The GENEActiv
      may provide an alternative, easy to wear device based measure for descriptive
      estimates of sedentary time in population samples.

PMID- 25956686
TI  - From humble beginnings to success in the clinic: Chimeric antigen receptor
      modified T-cells and implications for immunotherapy.
AB  - In the past 50 years, disease burden has steadily shifted from infectious disease
      to cancer. Standard chemotherapy has long been the mainstay of cancer medical
      management, and despite vast efforts towards more targeted and personalized drug
      therapy, many cancers remain refractory to treatment, with high rates of relapse
      and poor prognosis. Recent dramatic immunotherapy clinical trials have
      demonstrated that engineering T-cells with chimeric antigen receptors (CARs) to
      target CD19 can lead to complete remission in relapsed or refractory B-cell
      malignancies, generating a great deal of enthusiasm in the field. Here we provide
      a comprehensive overview of the history of adoptive T-cell therapy, including
      CARs, in solid tumors as well as hematologic malignancies. CAR therapy has the
      potential to fundamentally transform cancer treatment with specific and even
      personalized targeting of tissue- and tumor-specific antigens. However, before
      CARs become standard first-line treatment modalities, critical issues regarding
      efficacy, combinatorial regimens, and mechanisms of treatment failure and
      toxicity will need to be addressed. 

PMID- 25956688
TI  - Effectiveness of neuromuscular taping on pronated foot posture and walking
      plantar pressures in amateur runners.
AB  - OBJECTIVES: To determine the effect kinesiotaping (KT) versus sham kinesiotaping
      (sham KT) in the repositioning of pronated feet after a short running. DESIGN:
      Prospective, randomised, double-blinded, using a repeated-measures design with no
      cross-over. METHODS: 116 amateur runners were screened by assessing the post-run
      (45min duration) foot posture to identify pronated foot types (defined by Foot
      Posture Index [FPI] score of >=6). Seventy-three runners met the inclusion
      criteria and were allocated into two treatment groups, KT (n=49) and sham KT
      (n=24). After applying either the KT or sham KT and completing 45min of running
      (mean speed of 12km/h), outcome measures were collected (FPI and walking
      Pedobarography). RESULTS: FPI was reduced in both groups, more so in the KT group
      (mean FPI between group difference=0.9, CI 0.1-1.9), with a score closer to
      neutral. There were statistically significant differences between KT and sham KT
      (p<.05 and p<.01) in pressure time integral, suggesting that sham KT had a
      greater effect. CONCLUSIONS: KT may be of some assistant to clinicians in
      correction of pronated foot posture in a short-term. There was no effect of KT,
      however on pressure variables at heel strike or toe-off following a short
      duration of running, the sham KT technique had a greater effect. LEVEL OF
      EVIDENCE: Therapy, level 1b.

PMID- 25956689
TI  - Neuroepithelial structures associated with neurogenous subgemmal plaque of the
      tongue: an autopsy finding.

PMID- 25956690
TI  - 123I-MIBG Imaging: Patient Preparation and Technologist's Role.
AB  - The radiopharmaceutical (123)I-metaiodobenzylguanidine (MIBG) was approved by the
      Food and Drug Administration in March 2013 for the assessment of myocardial
      sympathetic innervation in the evaluation of patients with heart failure and an
      ejection fraction of no more than 35%. Almost any well-equipped nuclear medicine
      or nuclear cardiology laboratory can perform this test, although there is a need
      for special attention to patient preparation, dose calibration, and proper timing
      of the image acquisition. This article reviews the role of the nuclear medicine
      technologist and some practical aspects of cardiac sympathetic (123)I-MIBG
      imaging of which the laboratory team needs to be mindful. 

PMID- 25956692
TI  - An Analysis of 3 Common CardioGen-82 82Rb Infusion System Injection Methods and
      Their Impact on Clinical Volume and Image Counts.
AB  - In the wake of the Food and Drug Administration (FDA) recall, many clinics have
      had to reduce their examination volumes to meet the new generator volume usage
      requirements. This review tests 3 common infusion methods and how they affect
      patient dose, generator volume usage, image counts, and generator volume limits.
      METHODS: Three common configurations of the (82)Rb infusion system settings-
      standard 50-mL, volume-limiting, and bolus methods--were tested to determine how
      they affect patient dose, generator volume, and image counts. Each injection
      configuration was tested daily for the duration of 3 consecutive generators by
      injection into separate vials. Each injection configuration was also infused into
      a beaker and imaged to determine the impact of image counts for each method. The
      total estimated volumes for multiple examination and quality assurance clinical
      situations were simulated to observe the use of each method relative to the new
      FDA volume alert and expiration limits. RESULTS: Vial tests confirmed that the
      bolus method used the least amount of volume per infusion and stayed the most
      consistent throughout the life of the generator. The bolus method also produced a
      lower patient dose after approximately 10 d of use. The beaker tests in the
      scanner showed that the standard 50-mL method produced the greatest number of
      total counts for the flow and uptake images. On the basis of the estimated total
      volume simulations, the bolus method allowed for the most examinations over the
      life of the generator while staying within the new FDA limits. CONCLUSION: All 3
      methods for augmenting the (82)Rb infusion system produced different outcomes for
      patient dose, image counts, and total generator volume use. The standard 50-mL
      method ensured the maximum amount of counts available for imaging throughout the
      life of the generator. The bolus method provided a consistent and predictable
      amount of volume use. The volume-limiting method fell somewhere in the middle of
      volume predictability and count preservation.

PMID- 25956691
TI  - Geometric Calibration and Image Reconstruction for a Segmented Slant-Hole
      Stationary Cardiac SPECT System.
AB  - A dedicated stationary cardiac single-photon emission computed tomography (SPECT)
      system with a novel segmented slant-hole collimator has been developed. The goal
      of this paper is to calibrate this new imaging geometry with a point source.
      METHODS: Unlike the commercially available dedicated cardiac SPECT systems, which
      are specialized and can be used only to image the heart, our proposed cardiac
      system is based on a conventional SPECT system but with a segmented slant-hole
      collimator replacing the collimator. For a dual-head SPECT system, 2 segmented
      collimators, each with 7 sections, are arranged in an L-shaped configuration such
      that they can produce a complete cardiac SPECT image with only one gantry
      position. A calibration method was developed to estimate the geometric parameters
      of each collimator section as well as the detector rotation radius, under the
      assumption that the point source location is calculated using the central-section
      data. With a point source located off the rotation axis, geometric parameters for
      each collimator section can be estimated independently. The parameters estimated
      individually are further improved by a joint objective function that uses all
      collimator sections simultaneously and incorporates the collimator symmetry
      information. RESULTS: Estimation results and images reconstructed from estimated
      parameters are presented for both simulated and real data acquired from a
      prototype collimator. The calibration accuracy was validated by computer
      simulations with an error of about 0.1 degrees  for the slant angles and about 1
      mm for the rotation radius. Reconstructions of a heart-insert phantom did not
      show any image artifacts of inaccurate geometric parameters. CONCLUSION: Compared
      with the detector's intrinsic resolution, the estimation error is small and can
      be ignored. Therefore, the accuracy of the calibration is sufficient for cardiac
      SPECT imaging.

PMID- 25956693
TI  - 99mTc-Tilmanocept: A Novel Molecular Agent for Lymphatic Mapping and Sentinel
      Lymph Node Localization.
AB  - Preoperative lymphatic mapping in conjunction with intraoperative gamma-probe
      detection is widely used for sentinel node localization in melanoma, breast
      cancer, and other malignancies. (99m)Tc-radiocolloids have been the standard
      radiotracers used for sentinel node mapping. (99m)Tc-tilmanocept is a receptor
      binding molecular imaging agent approved by the U.S. Food and Drug Administration
      for lymphatic mapping and lymph node localization in breast cancer, melanoma,
      clinically node-negative squamous cell carcinoma of the oral cavity, and other
      solid tumors. It has several advantages over conventional radiocolloids,
      including rapid injection site clearance, high sentinel node extraction, and low
      distal node accumulation, which can lead to efficient resource use. 

PMID- 25956694
TI  - Publication productivity in nuclear medicine.
AB  - Publications form the knowledge base of any profession. Patterns in professional
      publications provide insight into the profession's maturity and global status. To
      our knowledge, publication productivity in nuclear medicine technology has not
      been reported. A recent study on publication productivity in radiography and
      radiation therapy provided interesting insight; however, a sampling bias resulted
      in study flaws. METHODS: The most productive medical radiation technologists were
      determined by collecting data from 7 key, international peer-reviewed journals
      for the medical radiation sciences over a 5-y period. A full list of the
      technologists' publications, for the 5-y period, was obtained using a PubMed and
      ResearchGate search, and the authors were analyzed. RESULTS: In total, 165
      medical radiation technologists were identified who had published 3 or more
      articles between 2009 and 2013. Of these authors, 55.2% (91/165) were
      radiographers, 35.2% (58/165) were radiation therapists, and 9.6% (16/165) were
      nuclear medicine technologists. Overall, the majority of the most prolific
      authors were academics (104/165; 63.0%). After we applied a correction factor
      (the productivity per member of the registered workforce), radiography had the
      fewest authors publishing, compared with the relative workflow sizes. CONCLUSION:
      Nuclear medicine technologists demonstrated a high degree of productivity both
      absolutely and relatively. Consequently, nuclear medicine technologists have a
      productive research culture and command a large footprint within and outside the
      key medical radiation science journals.

PMID- 25956695
TI  - Pharmacokinetics of enzalutamide, an anti-prostate cancer drug, in rats.
AB  - We characterized the pharmacokinetics of enzalutamide, a novel anti-prostate
      cancer drug, in rats after intravenous and oral administration in the dose range
      0.5-5 mg/kg. Tissue distribution, liver microsomal stability, and plasma protein
      binding were also examined. After intravenous injection, systemic clearance,
      volumes of distribution at steady state (Vss), and half-life (T1/2) remained
      unaltered as a function of dose, with values in the ranges of 80.4-86.3 mL/h/kg,
      1020-1250 mL/kg, and 9.13-10.6 h, respectively. Following oral administration,
      absolute oral bioavailability was 89.7 % and not dose-dependent. The recoveries
      of enzalutamide in urine and feces were 0.0620 and 2.04 %, respectively.
      Enzalutamide was distributed primarily in 10 tissues (brain, liver, kidneys,
      testis, heart, spleen, lungs, gut, muscle, and adipose) and tissue-to-plasma
      ratios of enzalutamide ranged from 0.406 (brain) to 10.2 (adipose tissue).
      Further, enzalutamide was stable in rat liver microsomes, and its plasma protein
      binding was 94.7 %. In conclusion, enzalutamide showed dose-independent
      pharmacokinetics at intravenous and oral doses of 0.5-5 mg/kg. Enzalutamide
      distributed primarily to 10 tissues and appeared to be eliminated primarily by
      metabolism. 

PMID- 25956696
TI  - Finding new scaffolds of JAK3 inhibitors in public database: 3D-QSAR models &
      shape-based screening.
AB  - The STAT/JAK3 pathway is a well-known therapeutic target in various diseases (ex.
      rheumatoid arthritis and psoriasis). The therapeutic advantage of JAK3 inhibition
      motivated to find new scaffolds with desired DMPK. For the purpose, in silico
      high-throughput sieves method is developed consisting of a receptor-guided three
      dimensional quantitative structure-activity relationship study and shape-based
      virtual screening. We developed robust and predictive comparative molecular field
      analysis (q (2) = 0.760, r (2) = 0.915) and comparative molecular similarity
      index analysis (q (2) = 0.817, r (2) = 0.981) models and validated these using a
      test set, which produced satisfactory predictions of 0.925 and 0.838,
      respectively. 

PMID- 25956697
TI  - Induction of human leukemia cell differentiation via PKC/MAPK pathways by
      arsantin, a sesquiterpene lactone from Artemisia santolina.
AB  - Sesquiterpene lactone compounds have received considerable attention in
      pharmacological research due to their therapeutic effects including anti-cancer
      and anti-inflammatory activities. In this report, we investigated the effect of
      arsantin, a sesquiterpene lactone compound present in Artemisia santolina, on
      cellular differentiation in the human promyelocytic leukemia HL-60 cell culture
      system. Arsantin significantly induced HL-60 cell differentiation in a
      concentration-dependent manner. Cytofluorometric analysis indicated that arsantin
      induced HL-60 cell differentiation predominantly into granulocytes. Both PKC and
      MAPK inhibitors suppressed the HL-60 cell differentiation induced by arsantin.
      Moreover, treatment with arsantin increased protein levels of PKCalpha and
      PKCbetaII isoforms, and also induced increased protein levels and phosphorylation
      form of MAPKs in HL-60 cells. Importantly, arsantin synergistically enhanced
      differentiation of HL-60 cells in a dose-dependent manner when combined with
      either low doses of 1,25-(OH)2D3 or ATRA. The ability to enhance the
      differentiation potential of 1,25-(OH)2D3 or ATRA by arsantin may improve
      outcomes in the therapy of acute promyelocytic leukemia. 

PMID- 25956698
TI  - A new serum cystatin C formula for estimating glomerular filtration rate in
      newborns.
AB  - BACKGROUND: The levels of serum cystatin C (CysC) and creatinine (Cr) were
      determined in small-for-gestational-age (SGA) babies and compared with those for
      normal term newborns appropriate for gestational age (AGA), at birth and 3 days
      later. We then compared a number of cysC-based, Cr-based and combined formulas
      for estimation of glomerular filtration rate (GFR) with the neonatal reference
      GFR. METHODS: Fifty full-term SGA and 50 AGA newborns were enrolled in the study.
      Kidney volume measurements were performed by ultrasound for each newborn.
      RESULTS: At birth, the mean level of CysC in SGA babies was 1.48 +/- 0.30 mg/l in
      cord blood and 1.38 +/- 0.18 mg/l in day 3 blood samples, and the mean Cr level,
      determined simultaneously, was 67.08 +/- 17.62 and 55.62 +/- 14.91 MUmol/l,
      respectively. These levels did not differ significantly from those determined in
      AGA babies. A 10 % reduction in kidney volume was associated with an increase in
      CysC value of 9.3 % in cord blood. The Cr-based and Schwartz-combined equations
      underestimated GFR relative to CysC-based and Zappitelli-based equations at birth
      and 3 days later. CONCLUSIONS: A newly constructed Cys-C based formula which
      includes kidney volume and body surface area in the calculations for GFR is a
      reliable marker of GFR compared with neonatal reference clearance values.

PMID- 25956699
TI  - Congenital nephrotic syndrome with dysmorphic features and death in early
      infancy: Answers.

PMID- 25956700
TI  - Protein intake in infancy and kidney size and function at the age of 6 years: The
      Generation R Study.
AB  - BACKGROUND: High protein intake has been linked to kidney growth and function.
      Whether protein intake is related to kidney outcomes in healthy children is
      unclear. METHODS: We examined the associations between protein intake in infancy
      and kidney outcomes at age 6 years in 2968 children participating in a population
      based cohort study. Protein intake at 1 year was assessed using a food-frequency
      questionnaire and was adjusted for energy intake. At age 6 years we measured the
      kidney volume and urinary albumin/creatinine ratio (ACR) of all participating
      children, and we estimated glomerular filtration rate (eGFR) using serum
      creatinine and cystatin C levels. RESULTS: In models adjusted for age, sex, body
      surface area, and sociodemographic factors, a higher protein intake was
      associated with a lower ACR and a higher eGFR but was not consistently associated
      with kidney volume. However, after further adjustment for additional dietary and
      lifestyle factors, such as sodium intake, diet quality, and television watching,
      higher protein intake was no longer associated with kidney function. No
      differences in associations were observed between animal and vegetable protein
      intake. CONCLUSIONS: Our findings show that protein intake in early childhood is
      not independently associated with kidney size or function at the age of 6 years.
      Further study is needed on other early life predictors of kidney size and
      function in later life.

PMID- 25956701
TI  - Management dilemmas in pediatric nephrology: Cystinosis.
AB  - BACKGROUND: Cystinosis is a rare, inherited autosomal recessive disease caused by
      the accumulation of free cystine in lysosomes. It is treated by the
      administration of cysteamine, which should be monitored by trough white blood
      cell (WBC) cystine measurements to ensure effective treatment. CASE
      DIAGNOSIS/TREATMENT: The index case had an older brother who had previously been
      diagnosed with cystinosis, allowing early diagnosis of the index case at the age
      of 5 months. Cysteamine therapy was started at the age of 3 years; however,
      monitoring of WBC cystine levels did not occur on a regular basis during most of
      his life. Growth retardation improved after correction of electrolyte
      disturbances, the initiation of cysteamine therapy and treatment with recombinant
      human growth hormone. Renal replacement therapy was started at the age of 11
      years, and renal transplantation was performed at the age of 12 years. Extra
      renal cystine accumulation caused multiple endocrinopathies (including adrenal
      insufficiency, hypothyroidism and primary hypogonadism), neurological symptoms,
      pancytopenia owing to splenomegaly and portal hypertension due to nodular
      regenerative hyperplasia, aggravated by splenic vein thrombosis and partial
      portal vein thrombosis. The patient died of diffuse intra-abdominal bleeding
      caused by severe portal hypertension. CONCLUSION: Cysteamine treatment should be
      started as early as possible, and dosage should be monitored and adapted based on
      trough WBC cystine levels. RELEVANT INTERNATIONAL GUIDELINE: Emma F et al. (2014)
      Nephropathic cystinosis: an international consensus document. Nephrol Dial
      Transplant 29:iv87-iv94.

PMID- 25956702
TI  - Accelerated rejection, thrombosis, and graft failure with angiotensin II type 1
      receptor antibodies.
AB  - BACKGROUND: Angiotensin II type 1 receptor antibodies (AT1R-Abs) have been
      implicated in renal transplant rejection and failure; however, the mechanism of
      allograft damage, patterns of clinical presentation, and response to
      desensitization of AT1R-Abs have not been clearly established. CASE
      DIAGNOSIS/TREATMENT: We present the case of a 7-year-old boy with preformed AT1R
      Abs who developed accelerated vascular and cellular rejection and renal allograft
      thrombosis despite desensitization and treatment with angiotensin receptor
      blockade. Although an association between AT1R-Abs and microvascular occlusion
      has been previously described, we are the first to describe an association
      between AT1R-Abs and renal artery thrombosis, leading to devastating early
      allograft failure. CONCLUSIONS: This case highlights the risk of allograft
      thrombosis associated with AT1R-Abs and illustrates that previous treatments
      utilized for AT1R-Abs may not always be effective. Further studies are needed to
      better characterize the mechanisms of AT1R-Ab pathogenesis and to establish safe
      levels of AT1R-Abs both pre- and post-transplantation. Given the outcome of this
      patient and the evidence of pro-coagulatory effects of AT1R-Abs, we suggest that
      the presence of AT1R-Ab may be a risk factor for thrombosis. The role of
      treatment with anti-coagulation and novel immunomodulatory agents such as
      tocilizumab and bortezomib require further investigation.

PMID- 25956703
TI  - mTOR-Dependent Suppression of Remnant Liver Regeneration in Liver Failure After
      Massive Liver Resection in Rats.
AB  - BACKGROUND AND AIMS: Massive hepatectomy often leads to fatal liver failure
      because of a small remnant liver volume. The aim of this study was to investigate
      the potential mechanisms leading to liver failure. METHODS: Sprague-Dawley rats
      had performed a sham operation, 85 % partial hepatectomy (PH) or 90 % PH, and all
      had free access to water with or without supplemented glucose. Liver function and
      survival were evaluated. Liver parenchymal injury was assessed by evaluating
      hepatic pathology, blood biochemistry, and apoptotic and necrotic alterations.
      The regeneration response was assessed by the weight gain of the remnant liver,
      hepatocyte proliferation markers, and regeneration-related molecules. RESULTS:
      The 90 % hepatectomy resulted in a significantly lower survival rate and impaired
      liver function; however, no significant more serious liver parenchymal injuries
      were detected. TNF-alpha, HGF, myc and IL-6 were either similarly expressed or
      overexpressed; however, the increase in remnant liver weight, mitotic index, and
      the presence of Ki-67 and PCNA were significantly lower in the 90 %
      hepatectomized rats. mTOR, p70S6K and 4EBP1 were not activated in the remnant
      liver after a 90 % hepatectomy as obviously as those after an 85 % hepatectomy,
      which was concomitant with the higher expression of phospho-AMPK and a lower
      intrahepatic ATP level. Glucose treatment significantly improved the survival
      rate of 90 %-hepatectomized rats. CONCLUSIONS: Suppression of remnant liver
      regeneration was observed in the 90 % PH and contributed to fatal liver failure.
      This suppressed liver regenerative capacity was related to the inhibited
      activation of mTOR signaling.

PMID- 25956704
TI  - Diabetes-related autoantibodies in diabetic gastroparesis.
AB  - BACKGROUND: Detection of islet autoantibodies [anti-glutamic acid decarboxylase
      antibody (GADA), anti-islet cell antibody (ICA), anti-insulin antibody (IAA)] in
      patients with diabetes usually indicates an autoimmune origin, suggesting type 1
      diabetes (T1DM). The aim of our study was to determine whether islet
      autoantibodies are present in patients with diabetic gastroparesis and whether
      they associate with delayed gastric emptying, severity of GI symptoms, or
      diagnosed type of diabetes. METHODS: Patients with diabetic gastroparesis
      completed: (1) Demographic Questionnaire assessing type of diabetes, associated
      symptoms and control of glucose and (2) Patient Assessment of GI Symptoms
      assessing symptoms severity. Blood was drawn for GADA, anti-islet cell ICA-IAA,
      and Hgb-A1c. Medical records were reviewed for gastric emptying tests and to
      confirm type of diabetes. RESULTS: Sixteen patients (12 T1DM; 4 diagnosed T2DM)
      with diabetic gastroparesis were evaluated. Six of the 16 patients tested
      positive for GADA, but none were positive for either ICA or IAA. Five of 12 T1DM
      patients had positive GADA, compared to one of four diagnosed as T2DM. The
      presence of antibodies was associated with the age of onset of gastroparesis
      symptoms, but not related to gastric emptying delay, symptom severity, HBA1c
      levels, or age. CONCLUSIONS: This pilot study demonstrated that of the three
      tested antibodies in long-term diabetic gastroparesis patients, GADA was the most
      prevalent positive antibody with no detection of ICA or IAA. Positive GADA was
      seen in 42 % of T1DM compared to 25 % of phenotypic T2DM. However, the presence
      of antibody was not associated with severity of gastric emptying or GI symptoms.
      Thus, detection of an autoimmune form of diabetes, primarily T1DM, should be
      investigated using GADA.

PMID- 25956705
TI  - Yield of Repeat Endoscopy in Barrett's Esophagus with No Dysplasia and Low-Grade
      Dysplasia: A Population-Based Study.
AB  - BACKGROUND: The yield of early repeat endoscopy in patients with Barrett's
      esophagus (BE) is not well established. AIMS: To determine how often early repeat
      endoscopy detected missed dysplasia or esophageal adenocarcinoma (EAC) in a
      population-based cohort of patients with BE. Secondary aims were to identify risk
      factors for missed dysplasia/EAC and compare detection of prevalent versus
      incident HGD/EAC. METHODS: A population-based cohort of BE subjects in Olmsted
      County, MN, was studied. Patients with initial non-dysplastic BE or low-grade
      dysplasia (LGD) who underwent repeat endoscopy within 24 months were included.
      Those with a worse histologic diagnosis on repeat endoscopy were considered to
      have missed dysplasia/EAC. Baseline characteristics among patients with and
      without missed dysplasia/EAC were compared. The absolute numbers of asymptomatic
      prevalent or missed, and incident HGD/EAC in the entire cohort were ascertained.
      RESULTS: Of 488 BE cases, 210 were included for the primary aim of this study.
      Repeat endoscopy revealed four HGD/EAC (1.9 %) and 16 LGD (8.8 %) for a combined
      miss rate of 9.5 %. Long-segment BE (LSBE) and lack of PPI use were predictors of
      missed dysplasia/EAC (P = 0.008), but adherence to biopsy protocol was not.
      Increased prevalent HGD/EAC (n = 30) rather than incident HGD/EAC (n = 22) was
      identified during a median 4.8 years of follow-up in this cohort. CONCLUSIONS:
      Dysplasia/EAC is commonly missed at initial BE diagnosis, particularly in
      patients with LSBE and no PPI use. Efforts should be made to enhance the
      sensitivity of detecting dysplasia/neoplasia around the time of initial BE
      diagnosis.

PMID- 25956706
TI  - Correlation of Biomarker Expression in Colonic Mucosa with Disease Phenotype in
      Crohn's Disease and Ulcerative Colitis.
AB  - BACKGROUND: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and
      ulcerative colitis (UC), are characterized by chronic intestinal inflammation due
      to immunological, microbial, and environmental factors in genetically predisposed
      individuals. Advances in the diagnosis, prognosis, and treatment of IBD require
      the identification of robust biomarkers that can be used for molecular
      classification of diverse disease presentations. We previously identified five
      genes, RELA, TNFAIP3 (A20), PIGR, TNF, and IL8, whose mRNA levels in colonic
      mucosal biopsies could be used in a multivariate analysis to classify patients
      with CD based on disease behavior and responses to therapy. AIM: We compared
      expression of these five biomarkers in IBD patients classified as having CD or
      UC, and in healthy controls. RESULTS: Patients with CD were characterized as
      having decreased median expression of TNFAIP3, PIGR, and TNF in non-inflamed
      colonic mucosa as compared to healthy controls. By contrast, UC patients
      exhibited decreased expression of PIGR and elevated expression of IL8 in colonic
      mucosa compared to healthy controls. A multivariate analysis combining mRNA
      levels for all five genes resulted in segregation of individuals based on disease
      presentation (CD vs. UC) as well as severity, i.e., patients in remission versus
      those with acute colitis at the time of biopsy. CONCLUSION: We propose that this
      approach could be used as a model for molecular classification of IBD patients,
      which could further be enhanced by the inclusion of additional genes that are
      identified by functional studies, global gene expression analyses, and genome
      wide association studies.

PMID- 25956707
TI  - Immediate effects of retinoic acid on gene expression in primary murine
      osteoblasts.
AB  - Consistent with clinical observations demonstrating that hypervitaminosis A is
      associated with increased skeletal fracture risk, we have previously found that
      dietary retinol deprivation partially corrects the bone mineralization defects in
      a mouse model of X-linked hypophosphatemic rickets. That retinol-dependent
      signaling pathways impact the skeleton is further supported by various findings
      demonstrating a negative influence of retinoic acid (RA) on bone-forming
      osteoblasts. We hypothesized that RA would directly regulate the expression of
      specific target genes in osteoblasts, and we aimed to identify these by genome
      wide expression analyses. Here we show that high dietary retinol intake in mice
      causes low bone mass associated with increased osteoclastogenesis and decreased
      osteoblastogenesis, but intact bone matrix mineralization. We additionally found
      that short-term treatment of primary osteoblasts with RA causes a rapid induction
      of specific genes involved in either retinol-dependent signaling (i.e. Rara,
      Crabp2) or skeletal remodeling (i.e. Twist2, Tnfsf11). In contrast, neither
      expression of established osteoblast differentiation markers nor the
      proliferation rate was immediately affected by RA administration. Collectively,
      our data suggest that the negative effects of vitamin A on skeletal integrity are
      explainable by an immediate influence of RA signaling on specific genes in
      osteoblasts that in turn influence bone remodeling. 

PMID- 25956708
TI  - Pilot study of modified FOLFOX6 adjuvant chemotherapy for high-risk rectal cancer
      treated with neoadjuvant chemoradiotherapy.
AB  - PURPOSE: Neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal
      excision is considered the standard of care for patients with locally advanced
      adenocarcinoma of the middle/low rectum. The present study evaluated the
      feasibility of using modified FOLFOX6 regimen as an adjuvant treatment for high
      risk patients with locally advanced rectal cancer (LARC) treated with neoadjuvant
      CRT. METHODS: Forty patients with LARC (ypT3-4 or N+) treated with neoadjuvant
      CRT were enrolled at Kyungpook National University Medical Center (Daegu, Korea)
      between December 2011 and December 2012. All the patients underwent rectal
      surgery with curative intent 8 weeks after the end of the neoadjuvant treatment.
      Adjuvant chemotherapy using modified FOLFOX6 regimen was then delivered for 3
      months. RESULTS: The treatments were generally well tolerated. Dose reduction was
      recorded in 11 of the 40 patients (27.5 %). The incidence of febrile neutropenia
      was 5 %, the incidence of grade 3 or 4 asthenia was 10 %, and the incidence of
      grade 3 gastrointestinal adverse events was 5 % during treatment. Treatment
      discontinuation caused by toxic effects or any other reasons was observed in six
      patients (15 %). The reasons for discontinuation were asthenia (n = 2, 5 %),
      diarrhea (n = 2, 5 %), acute renal failure (n = 1, 2.5 %), and relapse during
      chemotherapy (n = 1, 2.5 %). With a median follow-up duration of 18 months, six
      patients (15 %) relapsed and one patient (2.5 %) died of disease progression. The
      estimated 3-year disease-free survival and overall survival rates were 84.2 and
      97.3 %, respectively. CONCLUSIONS: Postoperative adjuvant modified FOLFOX6
      regimen was found to be feasible for patients with LARC treated with neoadjuvant
      CRT.

PMID- 25956709
TI  - Direct and indirect targeting of MYC to treat acute myeloid leukemia.
AB  - PURPOSE: Acute myeloid leukemia (AML) is the most common acute leukemia in adults
      and is often resistant to conventional therapies. The MYC oncogene is commonly
      overexpressed in AML but has remained an elusive target. We aimed to examine the
      consequences of targeting MYC both directly and indirectly in AML overexpressing
      MYC/Myc due to trisomy 8/15 (human/mouse), FLT3-ITD mutation, or gene
      amplification. METHODS: We performed in vivo knockdown of Myc (shRNAs) and both
      in vitro and in vivo experiments using four drugs with indirect anti-MYC
      activity: VX-680, GDC-0941, artemisinin, and JQ1. RESULTS: shRNA knockdown of Myc
      in mice prolonged survival, regardless of the mechanism underlying MYC
      overexpression. VX-680, an aurora kinase inhibitor, demonstrated in vitro
      efficacy against human MYC-overexpressing AMLs regardless of the mechanism of MYC
      overexpression, but was weakest against a MYC-amplified cell line. GDC-0941, a
      PI3-kinase inhibitor, demonstrated efficacy against several MYC-overexpressing
      AMLs, although only in vitro. Artemisinin, an antimalarial, did not demonstrate
      consistent efficacy against any of the human AMLs tested. JQ1, a bromodomain and
      extra-terminal bromodomain inhibitor, demonstrated both in vitro and in vivo
      efficacy against several MYC-overexpressing AMLs. We also confirmed a decrease in
      MYC levels at growth inhibitory doses for JQ1, and importantly, sensitivity of
      AML cell lines to JQ1 appeared independent of the mechanism of MYC
      overexpression. CONCLUSIONS: Our data support growing evidence that JQ1 and
      related compounds may have clinical efficacy in AML treatment regardless of the
      genetic abnormalities underlying MYC deregulation.

PMID- 25956710
TI  - Towards a genealogy of pharmacological practice.
AB  - Following Foucault's work on disciplinary power and biopolitics, this article
      maps an initial cartography of the research areas to be traced by a genealogy of
      pharmacological practice. Pharmacology, as a practical activity, refers to the
      creation, production and sale of drugs/medication. This work identifies five
      lines of research that, although often disconnected from each other, may be
      observed in the specialized literature: (1) pharmaceuticalization; (2) regulation
      of the pharmaceutical industry; (3) the political-economic structure of the
      pharmaceutical industry; (4) consumption/consumerism of medications; (5) and bio
      knowledge. The article suggests that a systematic analysis of these areas leads
      one to consider pharmacological practice a sui generis apparatus of power, which
      reaches beyond the purely disciplinary and biopolitical levels to encompass
      molecular configurations, thereby giving rise not only to new types of government
      over life, but also to new struggles for life, extending from molecular to
      population-wide levels. 

PMID- 25956711
TI  - Ocular wavefront analysis of aspheric compared with spherical monofocal
      intraocular lenses in cataract surgery: Systematic review with metaanalysis.
AB  - This review was conducted to compare the physical effect of aspheric IOL
      implantation on wavefront properties with that of spherical IOL implantation. The
      peer-reviewed literature was systematically searched in Medline, Embase, Web of
      Science, Biosis, and the Cochrane Library according to the Cochrane Collaboration
      method. Inclusion criteria were randomized controlled trials comparing the use of
      aspheric versus spherical monofocal IOL implantation that assessed visual acuity,
      contrast sensitivity, or quality of vision. A secondary outcome was ocular
      wavefront analysis; spherical aberration, higher-order aberrations (HOAs), coma,
      and trefoil were evaluated. Effects were calculated as standardized mean
      differences (Hedges g) and were pooled using random-effect models. Thirty-four of
      43 studies provided data for wavefront analysis. Aspheric monofocal IOL
      implantation resulted in less ocular spherical aberration and fewer ocular HOAs
      than spherical IOLs. This might explain the better contrast sensitivity in
      patients with aspheric IOLs.

PMID- 25956712
TI  - Cyclodialysis cleft with late hypotony maculopathy after inadvertent cannula
      detachment during cataract surgery.
AB  - We present the case of a 69-year-old woman who presented with hypotony several
      years after an inadvertent cannula detachment presumably formed a cyclodialysis
      cleft during phacoemulsification cataract extraction and posterior chamber
      intraocular lens implantation in her right eye. To our knowledge, this is the
      first report of late hypotony maculopathy as a result of inadvertent cannula
      release.

PMID- 25956713
TI  - Transscleral suture fixation following recurrent toric intraocular lens rotation.
AB  - We describe a surgical technique of transscleral suture fixation for recurrent
      rotation of a double-loop hydrophilic acrylic toric intraocular lens (IOL) in the
      capsular bag. Two 9-0 polypropylene sutures are placed in the proximal and distal
      angulations of 1 of the IOL haptics through the capsular bag. The clockwise and
      counterclockwise traction provided by these sutures prevents rotation of the IOL
      in either direction. This technique can be used in cases of spontaneous
      postoperative IOL rotation to achieve stabilization. In the case we describe, the
      IOL remained stable 11 months following transscleral suture fixation at the
      desired axis.

PMID- 25956714
TI  - The Reporting Of MEdication use in Observational studies (ROMEO) Statement.

PMID- 25956715
TI  - Analysis of evidence supporting the Federation of Bosnia and Herzegovina
      reimbursement medicines lists: role of the WHO Essential Medicines List, Cochrane
      systematic reviews and technology assessment reports.
AB  - PURPOSE: We compared recently introduced Basic Medicines Lists of the Federation
      of Bosnia and Herzegovina (BH) (FBH Basic Lists (FBLs)) with the World Health
      Organization (WHO) Essential Medicines List (EML) and the evidence supporting the
      inclusion of additional medicines on FBLs. METHODS: The sources of data included
      the 18th edition of the EML and the following FBLs: 2013 Hospital List, 2013 A
      List in Outpatient Setting, and 2012 List financed by the Federal Solidarity
      Fund. For medicines found on FBLs but not on EML, we searched the Cochrane
      Database of Systematic Reviews (CSR) and public health technology assessment
      (HTA) reports for evidence. RESULTS: FBLs had 134 medicines and 17 combinations
      that were not on EML, as well as 9 medicines deleted and 4 rejected from EML. EML
      had 82 medicines and 10 combinations of medicines not included in FBLs. Out of
      125 medicines on FBLs but not on EML, 52 (42%) had good CSR evidence supporting
      their inclusion (n = 38) or exclusion (n = 14). For the rest (n = 74), we found
      24 favourable HTA reports. For the total of 89 medicines (27%) listed on FBLs, we
      found no evidence (EML, CSR, HTA reports) good enough to justify their inclusion
      in FBLs. CONCLUSIONS: In circumstances of scarce financial resources, greater
      reliance on well-established, proven list is crucial. Independent, unbiased, high
      quality evidence such as WHO EML, CSR and HTA reports (national or international
      with local adaptations) should be used when deciding on medicine reimbursement.

PMID- 25956716
TI  - Small-study effects and time trends in diagnostic test accuracy meta-analyses: a
      meta-epidemiological study.
AB  - BACKGROUND: Small-study effects and time trends have been identified in meta
      analyses of randomized trials. We evaluated whether these effects are also
      present in meta-analyses of diagnostic test accuracy studies. METHODS: A
      systematic search identified test accuracy meta-analyses published between May
      and September 2012. In each meta-analysis, the strength of the associations
      between estimated accuracy of the test (diagnostic odds ratio (DOR), sensitivity,
      and specificity) and sample size and between accuracy estimates and time since
      first publication were evaluated using meta-regression models. The regression
      coefficients over all meta-analyses were summarized using random effects meta
      analysis. RESULTS: Forty-six meta-analyses and their corresponding primary
      studies (N = 859) were included. There was a non-significant relative change in
      the DOR of 1.01 per 100 additional participants (95% CI 1.00 to 1.03; P = 0.07).
      In the subgroup of imaging studies, there was a relative increase in sensitivity
      of 1.13 per 100 additional diseased subjects (95% CI 1.05 to 1.22; P = 0.002).
      The relative change in DOR with time since first publication was 0.94 per 5 years
      (95% CI 0.80 to 1.10; P = 0.42). Sensitivity was lower in studies published later
      (relative change 0.89, 95% CI 0.80 to 0.99; P = 0.04). CONCLUSIONS: Small-study
      effects and time trends do not seem to be as pronounced in meta-analyses of test
      accuracy studies as they are in meta-analyses of randomized trials. Small-study
      effects seem to be reversed in imaging, where larger studies tend to report
      higher sensitivity.

PMID- 25956717
TI  - Transfusion after acute upper gastrointestinal haemorrhage.

PMID- 25956718
TI  - Restrictive versus liberal blood transfusion for acute upper gastrointestinal
      bleeding (TRIGGER): a pragmatic, open-label, cluster randomised feasibility
      trial.
AB  - BACKGROUND: Transfusion thresholds for acute upper gastrointestinal bleeding are
      controversial. So far, only three small, underpowered studies and one single
      centre trial have been done. Findings from the single-centre trial showed reduced
      mortality with restrictive red blood cell (RBC) transfusion. We aimed to assess
      whether a multicentre, cluster randomised trial is a feasible method to
      substantiate or refute this finding. METHODS: In this pragmatic, open-label,
      cluster randomised feasibility trial, done in six university hospitals in the UK,
      we enrolled all patients aged 18 years or older with new presentations of acute
      upper gastrointestinal bleeding, irrespective of comorbidity, except for
      exsanguinating haemorrhage. We randomly assigned hospitals (1:1) with a computer
      generated randomisation sequence (random permuted block size of 6, without
      stratification or matching) to either a restrictive (transfusion when haemoglobin
      concentration fell below 80 g/L) or liberal (transfusion when haemoglobin
      concentration fell below 100 g/L) RBC transfusion policy. Neither patients nor
      investigators were masked to treatment allocation. Feasibility outcomes were
      recruitment rate, protocol adherence, haemoglobin concentration, RBC exposure,
      selection bias, and information to guide design and economic evaluation of the
      phase 3 trial. Main exploratory clinical outcomes were further bleeding and
      mortality at day 28. We did analyses on all enrolled patients for whom an outcome
      was available. This trial is registered, ISRCTN85757829 and NCT02105532.
      FINDINGS: Between Sept 3, 2012, and March 1, 2013, we enrolled 936 patients
      across six hospitals (403 patients in three hospitals with a restrictive policy
      and 533 patients in three hospitals with a liberal policy). Recruitment rate was
      significantly higher for the liberal than for the restrictive policy (62% vs 55%;
      p=0.04). Despite some baseline imbalances, Rockall and Blatchford risk scores
      were identical between policies. Protocol adherence was 96% (SD 10) in the
      restrictive policy vs 83% (25) in the liberal policy (difference 14%; 95% CI 7
      21; p=0.005). Mean last recorded haemoglobin concentration was 116 (SD 24) g/L
      for patients on the restrictive policy and 118 (20) g/L for those on the liberal
      policy (difference -2.0 [95% CI -12.0 to 7.0]; p=0.50). Fewer patients received
      RBCs on the restrictive policy than on the liberal policy (restrictive policy 133
      [33%] vs liberal policy 247 [46%]; difference -12% [95% CI -35 to 11]; p=0.23),
      with fewer RBC units transfused (mean 1.2 [SD 2.1] vs 1.9 [2.8]; difference -0.7
      [-1.6 to 0.3]; p=0.12), although these differences were not significant. We noted
      no significant difference in clinical outcomes. INTERPRETATION: A cluster
      randomised design led to rapid recruitment, high protocol adherence, separation
      in degree of anaemia between groups, and non-significant reduction in RBC
      transfusion in the restrictive policy. A large cluster randomised trial to assess
      the effectiveness of transfusion strategies for acute upper gastrointestinal
      bleeding is both feasible and essential before clinical practice guidelines
      change to recommend restrictive transfusion for all patients with acute upper
      gastrointestinal bleeding. FUNDING: NHS Blood and Transplant Research and
      Development.

PMID- 25956719
TI  - Assessment of immunotoxicity of dibutyl phthalate using live zebrafish embryos.
AB  - This study set out to understand the immune-toxic effects of dibutyl phthalate
      (DBP) using transgenic, albino or AB line zebrafish. Zebrafish embryos were
      exposed to different concentrations of DBP, and the immune cells formation,
      phagocytosis ability were measured after a short-term exposure to DBP for 6 h
      post-fertilization (hpf) to 72 or 96 hpf. Exposure to DBP was found to inhibit
      the neutrophils and macrophage formation in a concentration-dependent manner. The
      ability of macrophage phagocytosis was all decreased after exposure to DBP,
      indicating the occurrence of immunotoxicity. The respiratory burst was induced,
      and the transcription levels of T/B cell-related genes rag1/2 were up-regulated.
      The overall results indicate that DBP in aquatic environment greatly influence
      the immune system in fish, and zebrafish embryos can serve as a reliable model
      for the developmental immunotoxicity of toxic-chemicals.

PMID- 25956720
TI  - Effects of fenugreek (Trigonella foenum graecum) on gilthead seabream (Sparus
      aurata L.) immune status and growth performance.
AB  - The possible effect of dietary administration of fenugreek (Trigonella foenum
      graecum) on gilthead seabream (Sparus aurata L.) immune status and growth
      performance was studied. Fish were divided into 4 groups before being fed with
      commercial diet supplemented with 0% (control), 1%, 5% and 10% of fenugreek seeds
      for 4 weeks. The effects of the diets were analysed on the cellular (respiratory
      burst activity and leucocyte peroxidase content) and humoral (complement
      activity, antiprotease, total protein, peroxidase, and IgM level) immune
      parameters, as well as growth and haematological parameters (WBC and RBC counts).
      The results recorded enhancement in all the assayed parameters in fish fed
      fenugreek diets comparing to control fish. The expression of several immune
      related genes in head-kidney (MHC1, CSF-1R, IL-8, and IgM) and different
      antioxidant enzyme genes in liver (GR, CAT and SOD) of seabream specimens were
      also investigated. Again, the highest fenugreek doses tested provoked significant
      up-regulation in most of immune-related genes and antioxidant enzyme genes (p <
      0.05). No adverse effects were observed on intestine and liver morphology on fish
      fed fenugreek diets. The present results suggest that the fenugreek seed,
      specially the highest dosage used in the present work could be considered a good
      food supplement to improve the immune status and increase the production of
      gilthead seabream.

PMID- 25956721
TI  - Identification and functional characterization of the CSF1R gene from grass carp
      Ctenopharyngodon idellus and its use as a marker of monocytes/macrophages.
AB  - Colony-stimulating factor 1 receptor (CSF1R) is an important regulator of
      monocytes/macrophages (MO/MPhi). Although CSF1R gene has been identified and
      functionally studied in many fish, the precise role of CSF1R in grass carp
      (Ctenopharyngodon idellus) remains unclear. In this study, we determined the cDNA
      sequence of CSF1R (CiCSF1R) from a teleost fish, grass carp. Sequence comparison
      and phylogenetic tree analysis showed that CiCSF1R was most closely related to
      the CSF1R of zebrafish. The CiCSF1R transcript was mainly expressed in the
      spleen, head kidney, and head kidney-derived MO/MPhi, and its expression was
      altered in various tissues upon Aeromonas hydrophila infection. We prepared
      antibodies for neutralization of CiCSF1R on grass carp MO/MPhi. CiCSF1R
      neutralization or knockdown led to anti-inflammatory status in MO/MPhi upon A.
      hydrophila infection. CiCSF1R neutralization or knockdown also decreased the
      phagocytic activity of MO/MPhi. Flow cytometric analysis showed that more than
      85% of grass carp MO/MPhi were CiCSF1R-positive cells. The percentage of CiCSF1R
      positive cells in the head kidney of grass carp was above 10%, whereas it was
      only 5% and 4% in the spleen and liver, respectively. In conclusion, CSF1R is a
      specific surface marker of grass carp MO/MPhi, and it regulates the functions of
      MO/MPhi.

PMID- 25956722
TI  - Profiling immune response in zebrafish intestine, skin, spleen and kidney bath
      vaccinated with a live attenuated Vibrio anguillarum vaccine.

PMID- 25956723
TI  - Cluster Hepaticojejunostomy Is a Useful Technique Enabling Secure Reconstruction
      of Severely Damaged Hilar Bile Ducts.
AB  - Secure reconstruction of multiple hepatic ducts severely damaged by tumor
      invasion or iatrogenic injury is very difficult. If percutaneous or endoscopic
      biliary stenting fails, one or more percutaneous transhepatic biliary drainage
      (PTBD) tubes must be maintained in place for the rest of the patient's life. To
      cope with such difficult situations, we present a surgical technique termed
      cluster hepaticojejunostomy (HJ), which can be coupled with palliative bile duct
      resection. The cluster HJ technique consisted of applying multiple internal
      biliary stents and a single wide porto-enterostomy to surrounding connective
      tissues. We present a preliminary study with six patients. Five perihilar
      cholangiocarcinoma patients undergoing palliative bile duct resection received
      this procedure. Follow-up PTBD tubogram and hepatobiliary scintigraphy were
      performed at 1-2 weeks after surgery, after which the PTBD tubes were removed. No
      patient showed surgical complications, and the 6-month patency rate of clustered
      HJ was 80%. Another patient with laparoscopic cholecystectomy-associated major
      bile duct injury showed no biliary complications in the 5-year period following
      this procedure. Based on the results of this study, the cluster HJ technique may
      be a useful surgical method enabling the secure reconstruction of severely
      damaged hilar bile ducts.

PMID- 25956725
TI  - Should we restrict erythrocyte transfusion in early goal directed protocols?
AB  - BACKGROUND: Early goal-directed therapy has been endorsed in the guidelines of
      the Surviving Sepsis Campaign as a key strategy among patients presenting with
      severe sepsis or septic shock. But more importantly, early goal-directed therapy
      also became standard care for non-septic critically ill patients and was adopted
      for high-risk surgical patients. DISCUSSION: Importantly, transfusion of red
      blood cells is a central part of many protocols of early goal-directed therapy to
      indicate the need for use of inotropes and red blood cells, as both central
      venous saturation and hematocrit are used as transfusion triggers. However,
      burgeoning data has strongly linked transfusion with worse clinical outcomes. If
      correct, could these early goal-directed therapy 'bundles' have better outcome if
      a restrictive transfusion practice is adopted? SUMMARY: Early goal-directed
      therapy has evolved as standard care for most of critically ill patients, and
      many protocols contain transfusion of red blood cells targeting high hemoglobin
      level as a key element. As red blood cell transfusions are associated with
      increased morbidity and mortality, transfusion thresholds need to be more
      individualized.

PMID- 25956724
TI  - The Impact of Tumor Size on Long-Term Survival Outcomes After Resection of
      Solitary Hepatocellular Carcinoma: Single-Institution Experience with 2558
      Patients.
AB  - BACKGROUND: According to the 7th AJCC TNM staging system, solitary hepatocellular
      carcinoma (HCC) is classified as T1 or T2 based on microvascular invasion (MVI)
      regardless of tumor size. This study intended to evaluate the prognostic impact
      of tumor size on survival outcomes after macroscopic curative resection of
      solitary HCC. METHODS: Patients who underwent R0 resection of solitary HCC <10 cm
      (n = 2558) were selected for study. Follow-up lasted >=24 months or until death.
      RESULTS: HCC was detected during regular health screening or routine follow-up in
      2054 cases (80.3%). Hepatitis B virus (HBV) infection was associated in 2127
      (83.2%). Mean patient age was 54.4 +/- 9.9 years. Anatomical resection was
      performed in 1786 (69.8%). MVI was identified in 407 (16.0%) which therefore
      became stage T2; the other 2150 became stage T1. Tumor recurrence and patient
      survival rates were 24.9 and 95.0% after 1 year, 49.6 and 84.1% after 3 years,
      57.7 and 75.0 % after 5 years, and 67.3 and 56.6% after 10 years, respectively.
      Multivariate analysis showed that non-anatomical resection, MVI, and tumor size
      >5 cm were independent risk factors for both tumor recurrence and overall patient
      survival. Long-term survival correlated negatively with tumor size and MVI.
      Subgroup analysis with MVI and size cutoff of 5 cm revealed a significant
      survival difference (p = 0.000). Tumor size >5 cm was not a significant
      prognostic factor in non-HBV patients. CONCLUSIONS: These results suggest that
      the prognostic impact of tumor size may be underestimated in the current version
      of the AJCC staging system and that solitary HCC staging could be improved with
      inclusion of tumor size cutoff of 5 cm in HBV-associated patients. Further
      validation is necessary with multicenter studies.

PMID- 25956726
TI  - [Ulnar-sided wrist pain in sports: TFCC lesions and fractures of the hook of the
      hamate bone as uncommon diagnosis].
AB  - Injuries to the hand and wrist are common sports injuries. The diagnosis and
      therapy of wrist injuries are becoming more important, especially in increasingly
      more popular ball-hitting sports, such as golf, tennis and baseball. Ulnar-sided
      wrist pain is initially often misdiagnosed and treated as tenosynovitis or
      tendinitis but tears of the triangular fibrocartilage complex (TFCC) and
      fractures of the hook of hamate bone, which can also occur in these sports are
      seldomly diagnosed. The aim of this study was to conduct a systematic review of
      the literature focussing on TFCC lesions and fractures of the hook of the hamate
      bone in racquet sports, baseball and golf. A systematic review of the literature
      was performed in PubMed on the occurrence of TFCC lesions and fractures of the
      hook of the hamate bone. All studies and case reports were included. Because of
      the rarity of these injuries there were no exclusion criteria concerning the
      number of cases. Injuries associated with ball-hitting sports, such as TFCC
      lesions and fractures of hook of the hamate bone are still underrepresented in
      the current literature on sports injuries. The diagnosis and treatment of these
      injuries are often delayed and can severely handicap the performance and career
      of affected professional as well as amateur athletes. 

PMID- 25956727
TI  - Cost-effectiveness of a fixed-dose combination of solifenacin and oral controlled
      adsorption system formulation of tamsulosin in men with lower urinary tract
      symptoms associated with benign prostatic hyperplasia.
AB  - BACKGROUND: Storage symptoms, associated with benign prostatic hyperplasia (BPH),
      often co-exist with voiding symptoms in men with lower urinary tract symptoms
      (LUTS). Storage symptoms are likely to be most bothersome, and may not be
      adequately resolved by treatment with alpha-blocker or antimuscarinic
      monotherapy. A recent randomised controlled phase 3 trial (NEPTUNE) demonstrated
      that a fixed-dose combination (FDC) of solifenacin 6 mg plus an oral controlled
      absorption system (OCASTM) formulation of tamsulosin (TOCAS, 0.4 mg) improved
      storage symptoms, as well as quality of life, compared with TOCAS alone in men
      with moderate-to-severe storage symptoms and voiding symptoms. This analysis
      aimed to assess the cost-effectiveness of a FDC tablet of solifenacin 6 mg plus
      TOCAS relative to tolterodine plus tamsulosin given concomitantly, from the
      perspective of the UK National Health Service (NHS). METHODS: A Markov model was
      developed for men aged >=45 years with LUTS/BPH who have moderate-to-severe
      storage symptoms and voiding symptoms. The model calculated cost-effectiveness
      over an analytical time horizon of 1 year and estimated total treatment costs,
      quality adjusted life years (QALYs) and incremental cost-effectiveness ratio.
      RESULTS: The FDC tablet of solifenacin 6 mg plus TOCAS was associated with lower
      total annual costs (L860 versus L959) and increased QALYs (0.839 versus 0.836),
      and was therefore dominant compared with tolterodine plus tamsulosin. Time
      horizon, discontinuation or withdrawal rates, drug cost and utility values were
      the main drivers of cost-effectiveness. The probability that the FDC tablet of
      solifenacin 6 mg plus TOCAS is cost-effective was 100% versus tolterodine plus
      tamsulosin, at a willingness-to-pay threshold of L20,000/QALY gained.
      CONCLUSIONS: The FDC tablet of solifenacin 6 mg plus TOCAS provides important
      clinical benefits and is a cost-effective treatment strategy in the UK NHS
      compared with tolterodine plus tamsulosin for men with both storage and voiding
      LUTS/BPH.

PMID- 25956728
TI  - Severe Acute Orthopnea: Ipilimumab-Induced Bilateral Phrenic Nerve Neuropathy.
AB  - Ipilimumab is a monoclonal antibody used in the treatment of unresectable or
      metastatic melanoma. Several immune-related adverse events including potential
      fatal events have been reported following its use. We report a case of a 66-year
      old man who presented with severe acute exertional dyspnea and orthopnea
      following administration of ipilimumab for metastatic melanoma. Although various
      peripheral neuropathy syndromes associated with ipilimumab have been reported,
      bilateral phrenic nerve paralysis has not been previously reported. This case
      also highlights the clinical features of bilateral phrenic nerve neuropathy.
      Pulmonologists have to be aware of these unusual immune-related respiratory
      adverse events in patients being treated with monoclonal antibodies. 

PMID- 25956730
TI  - IGFBP special issue - introduction.

PMID- 25956729
TI  - First learned words are not forgotten: Age-of-acquisition effects in the tip-of
      the-tongue experience.
AB  - A large body of evidence indicates that the age at which a word is acquired
      predicts the time required to retrieve that word during speech production. Here
      we explored whether age of acquisition also predicts the experience of being
      unable to produce a known word at a particular moment. Italian speakers named a
      sequence of pictures in Experiment 1 or retrieved a word as a response to a
      definition in Experiment 2. In both experiments, the participants were instructed
      to indicate when they were in a tip-of-the-tongue (TOT) state. Generalized mixed
      effects models performed on the TOT and correct responses revealed that word
      frequency and age of acquisition predicted the TOT states. Specifically, low
      frequency words elicited more TOTs than did high-frequency words, replicating
      previous findings. In addition, late-acquired words elicited more TOTs than did
      early-acquired words. Further analyses revealed that the age of acquisition was a
      better predictor of TOTs than was word frequency. The effects of age of
      acquisition were similar with subjective and objective measures of age of
      acquisition, and persisted when several psycholinguistic variables were taken
      into consideration as predictors in the generalized mixed-effects models. We
      explained these results in terms of weaker semantic-to-phonological connections
      in the speech production system for late-acquired words. 

PMID- 25956731
TI  - IL-1beta enhances vascular smooth muscle cell proliferation and migration via
      P2Y2 receptor-mediated RAGE expression and HMGB1 release.
AB  - Vascular smooth muscle cells (VSMCs) are the major cell type in blood vessel
      walls, and their proliferation and migration play important roles in the
      development of atherosclerosis. Recently, it has been reported that IL-1beta
      mediates the inflammatory response through the upregulation of the P2Y2 receptor
      (P2Y2R). Thus, we examined the role of P2Y2R in IL-1beta-mediated proliferation
      and migration of VSMCs and the underlying molecular mechanisms. VSMCs were
      pretreated with IL-1beta for 24h to upregulate P2Y2R expression. The cells were
      then stimulated with UTP or ATP for the indicated times, and cell proliferation
      and migration and the related signaling pathways were examined. The equipotent
      P2Y2R agonists ATP and UTP enhanced proliferation, RAGE expression and HMGB1
      secretion in IL-1beta-pretreated VSMCs. Additionally, pretreatment with IL-1beta
      enhanced UTP-mediated VSMC migration and MMP-2 release, but these effects were
      not observed in the P2Y2R-siRNA- or RAGE-siRNA-transfected VSMCs. Next, the
      signaling molecules involved in P2Y2R-mediated cell proliferation and migration
      were determined. The ERK, AKT, PKC, Rac-1 and ROCK2 pathways were involved in UTP
      induced cell proliferation and migration, MMP-2 and HMGB1 secretion and RAGE
      expression in the IL-1beta-pretreated VSMCs. UTP induced the phosphorylation of
      ERK, AKT and PKC and the translocation of Rac-1 and ROCK2 from cytosol to
      membrane as well as stress fiber formation, which were markedly increased in the
      IL-1beta-pretreated VSMCs but not in the P2Y2R-siRNA-transfected VSMCs. These
      results demonstrate that pro-inflammatory cytokines associated with
      atherosclerosis, such as IL-1beta, can accelerate the process of atherosclerosis
      through the upregulation of P2Y2R. 

PMID- 25956732
TI  - Wogonin inhibits LPS-induced vascular permeability via suppressing MLCK/MLC
      pathway.
AB  - Wogonin, a naturally occurring monoflavonoid extracted from the root of
      Scutellaria baicalensis Georgi, has been shown to have anti-inflammatory and anti
      tumor activities and inhibits oxidant stress-induced vascular permeability.
      However, the influence of wogonin on vascular hyperpermeability induced by
      overabounded inflammatory factors often appears in inflammatory diseases and
      tumor is not well known. In this study, we evaluate the effects of wogonin on LPS
      induced vascular permeability in human umbilical vein endothelial cells (HUVECs)
      and investigate the underlying mechanisms. We find that wogonin suppresses the
      LPS-stimulated hyperactivity and cytoskeleton remodeling of HUVECs, promotes the
      expression of junctional proteins including VE-Cadherin, Claudin-5 and ZO-1, as
      well as inhibits the invasion of MDA-MB-231 across EC monolayer. Miles vascular
      permeability assay proves that wogonin can restrain the extravasated Evans in
      vivo. The mechanism studies reveal that the expressions of TLR4, p-PLC, p-MLCK
      and p-MLC are decreased by wogonin without changing the total steady state
      protein levels of PLC, MLCK and MLC. Moreover, wogonin can also inhibit KCl
      activated MLCK/MLC pathway, and further affect vascular permeability.
      Significantly, compared with wortmannin, the inhibitor of MLCK/MLC pathway,
      wogonin exhibits similar inhibition effects on the expression of p-MLCK, p-MLC
      and LPS-induced vascular hyperpermeability. Taken together, wogonin can inhibit
      LPS-induced vascular permeability by suppressing the MLCK/MLC pathway, suggesting
      a therapeutic potential for the diseases associated with the development of both
      inflammatory and tumor. 

PMID- 25956733
TI  - Prevalence and predictors of high-on treatment platelet reactivity with
      ticagrelor in ACS patients undergoing stent implantation.
AB  - BACKGROUND: Residual high-on treatment platelet reactivity (HRPR) predicts
      outcomes and major cardiovascular events. Ticagrelor has provided pharmacological
      and clinical evidence of more predictable and more potent antiplatelet effect as
      compared to clopidogrel. However, so far, few data have investigated the
      prevalence and predictors of HRPR in unselected patients treated with ticagrelor,
      that is therefore the aim of the current study. METHODS AND RESULTS: Our
      population is represented by 195 patients undergoing coronary stenting for ACS
      and receiving ASA and ticagrelor. Platelet function was assessed by multiplate
      impedance aggregometry (MEA) between 1 and 3months after stenting. Main clinical
      features and biochemistry parameters were collected. HRPR for ticagrelor was
      defined for aggregation>417 AUC after MEA-ADP stimulation. A total of 26
      patients, (13.3%), displayed HRPR with ticagrelor. Older age (>=70years,
      p=0.002), hypertension (p=0.02) previous myocardial infarction (p=0.04), therapy
      with nitrates and beta-blockers (p=0.02), diuretics (p=0.03) and fasting
      glycaemia (p=0.05) were associated to HRPR with ticagrelor. By multivariate
      analysis, age>=70years (OR [95%CI]=4.6[1.55-13.8], p=0.006), concomitant therapy
      with beta-blockers (OR [95%CI]=3.2[1.06-9.6], p=0.04) and platelets count
      (OR[95%CI]=1.0007 [1-1.016], p=0.05) were identified as independent predictors of
      HRPR with ticagrelor. CONCLUSION: The present study firstly demonstrates that the
      occurrence of HRPR in patients treated with ticagrelor is not so futile, as it
      was observed in 13% of patients treated with ticagrelor. Older age, beta-blockers
      administration and platelets count are independent predictors of HRPR with
      ticagrelor.

PMID- 25956734
TI  - Aberrant mitochondrial RNA in the role of aging and aging associated diseases.
AB  - Accumulations of mitochondrial DNA (mtDNA) mutations associated with aging are
      evident in multiple human tissues. The role of mtDNA mutations can be observed in
      an aging animal model such as homozygous knock-in PolgA mice, which have a large
      colonial expansion of mtDNA mutations. They develop reduced lifespan and
      premature onset of age-related phenotypes, that are also observed in clinical
      practice like mitochondrial aging acceleration with anti-retroviral therapy
      through clonal expansion of mtDNA mutations. These clonally expanded mtDNA
      mutations maintain transcription ability which could result in an accumulation of
      abnormal mitochondrial RNA (mtRNA) in the affected cells. Compensation-effect
      doctrine states that accumulated mtDNA mutations in the cell must reach a set
      threshold before they have a negative effect on cell function due to compensation
      effects from normal cellular mtDNA. In contrast to this theory, we suggest that
      an accumulation of aberrant mtRNA transcribed from mtDNA mutations negatively
      influences cellular function through complex internal and external mitochondrial
      pathways, and might be an important cause of aging and aging-associated diseases.

PMID- 25956735
TI  - Is nonalcoholic fatty liver disease an endogenous alcoholic fatty liver disease? 
      A mechanistic hypothesis.
AB  - Nonalcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD)
      are so similar that only a detailed history of alcohol intake can distinguish one
      from the other. Because subjects with NAFLD produce significantly more endogenous
      ethanol (EE) than controls, some researchers suspected that these similarities
      are not merely coincidental. For this reason, it was attempted to show that NAFLD
      is actually an endogenous alcoholic fatty liver disease (EAFLD). However,
      negligible blood-alcohol concentration (BAC) and the inability of gut microbiota
      to produce hepatotoxic concentrations of EE rejected this hypothesis. To clarify
      these conflicting results, we provide a mechanistic framework explaining how
      NAFLD may be an EAFLD. First of all, the key finding is that ethanol is a
      prodrug, enabling the idea that AFLD may develop with negligible/absent BAC.
      Second, extrahepatic acetaldehyde (ACD) alone recapitulates AFLD and is about 330
      fold more hepatotoxic than that generated inside the liver. Third, gut microbiota
      can even produce much larger amounts of EE than those currently considered
      cirrhotogenic for man. Fourth, an extensive gut-liver axis first-pass metabolism
      of ethanol prevents the development of significant BAC in NAFLD. Fifth, all genes
      involved in EE metabolism are upregulated in the livers of patients with
      nonalcoholic steatohepatitis (NASH). Last, overexpression of the gene encoding
      alcohol dehydrogenase (ADH) 4 implicates liver exposure to high concentrations of
      EE. In conclusion, this work provides mechanistic explanation supporting the
      assumption that NAFLD may indeed be an EAFLD. If validated by further testing,
      the hypothesis may help develop novel therapeutic and preventive strategies
      against this ubiquitous condition. 

PMID- 25956736
TI  - Brown adipocytes, cardiac protection and a common adipo- and myogenic stem
      precursor in aged human hearts.
AB  - New data on adult stem cells (ASCs) are continuously added by research for use in
      regenerative medicine. However organ-specific ASC markers are incompletely
      explored. It was demonstrated that in non-cardiac brown adipose tissue (BAT)
      CD133+ cells differentiate in cardiomyocytes, and such BAT-derived cells induce
      bone marrow-derived cells into cardiomyocytes, thus being a promising source for
      cardiac stem cell therapy. During embryogenesis the subepicardial fat derives
      from BAT. Although it was not specifically investigated in human adult or aged
      hearts, it is actually known that metabolically active BAT can be found in many
      adult humans, is related to antiobesity effects, and it may derive from
      stem/progenitor cells. Stro-1 can safely identify in situ cardiac stem cells
      (CSCs) with myogenic and adipogenic potential. It was therefore raised the
      hypothesis of subepicardial differentiation of CSCs in BAT in adult/aged hearts,
      which could be viewed, such as in infants, as a mechanism of protection. This
      could be determined by the reactivation of an embryologic differentiation pattern
      in which brown adipocytes and muscle cells derive from a common stem ancestor.
      Such quiescent common stem ancestors could be suggested in adult, or aged, human
      hearts, when subepicardial BAT is found, and if a Stro-1+/CD133+/Isl-1+ phenotype
      of CSCs is determined. 

PMID- 25956738
TI  - Interaction between Hanseniaspora uvarum and Saccharomyces cerevisiae during
      alcoholic fermentation.
AB  - During wine fermentation, Saccharomyces clearly dominate over non-Saccharomyces
      wine yeasts, and several factors could be related to this dominance. However, the
      main factor causing the reduction of cultivable non-Saccharomyces populations has
      not yet been fully established. In the present study, various single and mixed
      fermentations were performed to evaluate some of the factors likely responsible
      for the interaction between Saccharomyces cerevisiae and Hanseniaspora uvarum.
      Alcoholic fermentation was performed in compartmented experimental set ups with
      ratios of 1:1 and 1:9 and the cultivable population of both species was followed.
      The cultivable H. uvarum population decreased sharply at late stages when S.
      cerevisiae was present in the other compartment, similarly to alcoholic
      fermentations in non-compartmented vessels. Thus, cell-to-cell contact did not
      seem to be the main cause for the lack of cultivability of H. uvarum. Other
      compounds related to fermentation performance (such as sugar and ethanol) and/or
      certain metabolites secreted by S. cerevisiae could be related to the sharp
      decrease in H. uvarum cultivability. When these factors were analyzed, it was
      confirmed that metabolites from S. cerevisiae induced lack of cultivability in H.
      uvarum, however ethanol and other possible compounds did not seem to induce this
      effect but played some role during the process. This study contributes to a new
      understanding of the lack of cultivability of H. uvarum populations during the
      late stages of wine fermentation. 

PMID- 25956737
TI  - Novel DNA packaging recognition in the unusual bacteriophage N15.
AB  - Phage lambda's cosB packaging recognition site is tripartite, consisting of 3
      TerS binding sites, called R sequences. TerS binding to the critical R3 site
      positions the TerL endonuclease for nicking cosN to generate cohesive ends. The
      N15 cos (cos(N15)) is closely related to cos(lambda), but whereas the cosB(N15)
      subsite has R3, it lacks the R2 and R1 sites and the IHF binding site of
      cosB(lambda). A bioinformatic study of N15-like phages indicates that cosB(N15)
      also has an accessory, remote rR2 site, which is proposed to increase packaging
      efficiency, like R2 and R1 of lambda. N15 plus five prophages all have the rR2
      sequence, which is located in the TerS-encoding 1 gene, approximately 200 bp
      distal to R3. An additional set of four highly related prophages, exemplified by
      Monarch, has R3 sequence, but also has R2 and R1 sequences characteristic of cosB
      lambda. The DNA binding domain of TerS-N15 is a dimer.

PMID- 25956739
TI  - Prospective randomised trial comparing unlinked, modular bicompartmental knee
      arthroplasty and total knee arthroplasty: a five years follow-up.
AB  - BACKGROUND: A significant proportion of patients with knee osteoarthritis have
      articular degeneration that is limited to the medial and patellofemoral
      compartments. The objective of this study was to compare clinical outcomes of
      unlinked bicompartmental knee arthroplasty (BCA) and total knee arthroplasty
      (TKA) at 5years in this subset of patients. METHODS: 48 patients were randomised
      into two groups: unlinked, modular bicompartmental arthroplasty and total knee
      arthroplasty. Data on demographics and clinical outcomes were collected (Bartlett
      Knee Score, Oxford Knee Score, Knee Society Score). Data on intra-operative blood
      loss in both groups were also recorded. RESULTS: Out of the 48 patients, 26
      underwent BCA and 22 had TKA. Both groups shared similar demographic profiles. At
      five years post surgery, there was significant improvement across all functional
      scores in both groups. However, there was no significant difference in outcome
      scores in the BCA group compared to the TKA group. The drop in serum haemoglobin
      levels postoperatively was 1.55 and 2.30g/dl for the BCA and TKA groups
      respectively (p<.001). The total amount of blood loss was 397 and 647ml
      respectively (p=.001). CONCLUSIONS: Unlinked, modular BCA results in similar
      clinical and functional scores as TKA for medial and patellofemoral arthritis in
      the mid-term. Intra-operative blood loss was significantly lower in the BCA group
      compared to the TKA group. BCA is a viable option for a select group of young and
      active patients with the advantage of reduced intra-operative blood loss and
      equivalent functional outcomes as TKA.

PMID- 25956740
TI  - Late antibody-mediated rejection after heart transplantation: Mortality, graft
      function, and fulminant cardiac allograft vasculopathy.
AB  - BACKGROUND: Late antibody-mediated rejection (AMR) after heart transplantation is
      suspected to be associated with a poor short-term prognosis. METHODS: A
      retrospective single-center observational study was performed. Late AMR was
      defined as AMR occurring at least 1 year after heart transplantation. The study
      included all consecutive patients with proven and treated late acute AMR at the
      authors' institution between November 2006 and February 2013. The aim was to
      analyze the prognosis after late AMR, including mortality, recurrence of AMR,
      left ventricular ejection fraction, and cardiac allograft vasculopathy (CAV).
      Selected endomyocardial biopsy specimens obtained before AMR were also blindly
      reviewed to identify early histologic signs of AMR. RESULTS: The study included
      20 patients treated for late AMR. Despite aggressive immunosuppressive therapies
      (100% of patients received intravenous methylprednisolone, 90% received
      intravenous immunoglobulin [IVIg],85% received plasmapheresis, 45% received
      rituximab), the prognosis remained poor. Survival after late AMR was 80% at 1
      month, 60% at 3 months, and 50% at 1 year. All early deaths (<3 months, n = 8)
      were directly attributable to graft dysfunction or to complication of the intense
      immunosuppressive regimen. Among survivors at 3 months (n = 12), histologic
      persistence or recurrence of AMR, persistent left ventricular dysfunction, and
      fulminant CAV were common (33%, 33%, and 17% of patients). Microvascular
      inflammation was detected in at least 1 biopsy specimen obtained before AMR in 13
      patients (65%). CONCLUSIONS: Prognosis after late AMR is poor despite aggressive
      immunosuppressive therapies. Fulminant CAV is a common condition in these
      patients. Microvascular inflammation is frequent in endomyocardial biopsy
      specimens before manifestation of symptomatic AMR.

PMID- 25956741
TI  - Inhibition of the ERCC1-XPF structure-specific endonuclease to overcome cancer
      chemoresistance.
AB  - ERCC1-XPF is a structure-specific endonuclease that is required for the repair of
      DNA lesions, generated by the widely used platinum-containing cancer
      chemotherapeutics such as cisplatin, through the Nucleotide Excision Repair and
      Interstrand Crosslink Repair pathways. Based on mouse xenograft experiments,
      where ERCC1-deficient melanomas were cured by cisplatin therapy, we proposed that
      inhibition of ERCC1-XPF could enhance the effectiveness of platinum-based
      chemotherapy. Here we report the identification and properties of inhibitors
      against two key targets on ERCC1-XPF. By targeting the ERCC1-XPF interaction
      domain we proposed that inhibition would disrupt the ERCC1-XPF heterodimer
      resulting in destabilisation of both proteins. Using in silico screening, we
      identified an inhibitor that bound to ERCC1-XPF in a biophysical assay, reduced
      the level of ERCC1-XPF complexes in ovarian cancer cells, inhibited Nucleotide
      Excision Repair and sensitised melanoma cells to cisplatin. We also utilised high
      throughput and in silico screening to identify the first reported inhibitors of
      the other key target, the XPF endonuclease domain. We demonstrate that two of
      these compounds display specificity in vitro for ERCC1-XPF over two other
      endonucleases, bind to ERCC1-XPF, inhibit Nucleotide Excision Repair in two
      independent assays and specifically sensitise Nucleotide Excision Repair
      proficient, but not Nucleotide Excision Repair-deficient human and mouse cells to
      cisplatin. 

PMID- 25956742
TI  - Systematic review of coaching to enhance surgeons' operative performance.
AB  - BACKGROUND: There is increasing attention on the coaching of surgeons and
      trainees to improve performance but no comprehensive review on this topic. The
      purpose of this review is to summarize the quantity and the quality of studies
      involving surgical coaching methods and their effectiveness. METHODS: We
      performed a systematic literature search through PubMed and PsychINFO by using
      predefined inclusion criteria. Evidence for main outcome categories was evaluated
      with the Grading of Recommendations Assessment, Development, and Evaluation
      (GRADE) system and the Medical Education Research Study Quality Instrument
      (MERSQI). RESULTS: Of a total 3,063 articles, 23 met our inclusion criteria; 4
      randomized controlled trials and 19 observational studies. We categorized the
      articles into 4 groups on the basis of the outcome studied: perception, attitude
      and opinion; technical skills; nontechnical skills; and performance measures.
      Overall strength of evidence for each outcome groups was as follows: Perception,
      attitude, and opinion (Grading of Recommendations Assessment, Development, and
      Evaluation: Very Low, Medical Education Research Study Quality Instrument
      [MERSQI]: 10); technical skills (randomized controlled trials: High, 13.1;
      Observation studies: Very Low, 11.5); nontechnical skills (Very Low, 12.4) and
      performance measures (Very Low, 13.6). Simulation was the most used setting for
      coaching; more than half of the studies deployed an experienced surgeon as a
      coach and showed that coaching was effective. CONCLUSION: Surgical coaching
      interventions have a positive impact on learners' perception and attitudes, their
      technical and nontechnical skills, and performance measures. Evidence of impact
      on patient outcomes was limited, and the quality of research studies was
      variable. Despite this, our systematic review of different coaching interventions
      will benefit future coaching strategies and implementation to enhance operative
      performance.

PMID- 25956743
TI  - Reappraisal of pancreatic enucleations: A single-center experience of 126
      procedures.
AB  - BACKGROUND: Parenchyma-sparing pancreatectomies, especially enucleations, could
      avoid disappointing functional results associated with standard resections for
      benign/low-grade pancreatic neoplasms. This study aimed to assess short- and long
      term outcomes in a large, single-center series of enucleations. METHODS: All 126
      patients who underwent enucleation for benign/low-grade neoplasms between 1996
      and 2011 were included retrospectively. RESULTS: Lesions were mainly incidentally
      diagnosed (71%), most often located in the head (46%), and with a median size of
      20 mm. Enucleations were mainly performed for branch-duct intraductal papillary
      mucinous neoplasm (30%), nonfunctioning pancreatic neuroendocrine tumors (29%),
      and mucinous cystadenoma (21%). Overall mortality was 0.8% and morbidity 63%,
      mainly owing to pancreatic fistula (57%). Most were significant clinically, that
      is, grade B or C (41%), but managed conservatively (85%). Reoperation rate was
      3%, mainly owing to hemorrhage. Postoperative de novo diabetes was 0.8%, and
      exocrine insufficiency never observed. The 1-, 3-, and 5-year recurrence-free
      survival were 100%, 98%, and 93%, respectively. CONCLUSION: Enucleation is
      associated with substantial morbidity, especially pancreatic fistula.
      Enucleations as an alternative to standard resection are best indicated for
      small, benign, and low-grade lesions located far from the main pancreatic duct.
      Enucleations should be proposed to young and fit patients able to tolerate
      postoperative morbidity and who could benefit from the excellent long-term
      results.

PMID- 25956744
TI  - [Blood transfusion and inflammation as of yesterday, today and tomorrow].
AB  - Blood transfusion is made possible principally by use of donated homologous
      components that - in turn - can be perceived as sources of danger by recipients.
      This may create an innate immune response dominated by inflammation, especially
      when transfusion is repeated. Residual leukocytes in blood components can source
      inflammatory lesions but considerably less than used to be prior to systematic,
      early and stringent - in process - leukoreduction. Every blood component can
      cause inflammation, though barely in the case of therapeutic plasma (in such a
      case, this is mainly restricted to allergy). Iron that may be freed by red blood
      cells but also processing and storage lesions such as the emission of
      microparticles can reveal themselves as pro-inflammatory. Platelets in platelet
      components represent the main source of inflammatory and/or allergic hazards in
      transfusion; this is linked with processing and storage lesions but also with the
      platelet physiology itself. It is of utmost importance to avoid inflammatory
      adverse events in patients that are fragile because of their primary condition
      and/or treatment; this stands for their safety, as inflammation can be extremely
      severe and even lethal, and also for their comfort; this increases efficacy of
      transfusion programs while reducing the overall costs.

PMID- 25956745
TI  - Development of titanium oxide layer containing nanocrystalline zirconia particles
      with tetragonal structure: Structural and biological characteristics.
AB  - This study investigated the microstructural, mechanical and biological properties
      of oxide layers containing tetragonal zirconia (t-ZrO2) particles on pure
      titanium produced by plasma electrolytic oxidation (PEO) process. For this
      purpose, PEO processes were carried out at an AC current density of 200mA/cm(2)
      for 180s in potassium pyrophosphate (K4P2O7) electrolytes with and without t-ZrO2
      powder. Structural investigations using transmission electron microscopy
      exhibited that the present nanocrystalline oxide layer evidenced the successful
      incorporation of a myriad of t-ZrO2 particles working as an intermediate medium
      to reinforce the adhesion strength between the substrate and oxide layer.
      Regarding biomimetic apatite formation, the t-ZrO2 particles uniformly spread
      were of considerable importance in triggering the nucleation and growth of
      biomimetic apatite on the surface of the oxide layer immersed in a simulated body
      fluid solution. The growth and proliferation rates of the osteoblasts (MC3T3-E1)
      cultured on the oxide layer with t-ZrO2 particles were higher than that without t
      ZrO2 particles due to the higher roughness providing the better sites for the
      filopodia extension and interlocking. 

PMID- 25956746
TI  - Estimation of the adhesive force distribution for the flagellar adhesion of
      Escherichia coli on a glass surface.
AB  - The effects of the presence or absence of microbial flagella and the microbial
      motility on the colloidal behaviors of microbial cells were quantitatively
      evaluated. The microbial cell attachment and detachment processes on a glass
      surface were observed directly using a parallel-plate flow chamber. Wild-type,
      flagellar paralyzed, and nonflagellated Escherichia coli strains were used as
      model microbial cells. In the cell attachment tests, the microbial adhesion rate
      in a 160mM NaCl solution was approximately 10 times higher than that in a 10mM
      solution, for all E. coli strains. The colloidal behavior of the microbial cells
      agreed well with the predictions of the DLVO theory. In addition, the microbial
      flagella and motility did not significantly affect the cell attachment,
      regardless of the existence of a potential barrier between the cell and the glass
      substratum. In the cell detachment tests, the cumulative number of microbial
      cells detached from the glass substratum with increasing flow rate was fit well
      with the Weibull distribution function. The list of strains arranged in order of
      increasing median drag force required to remove them was nonflagellated strain,
      flagellar paralyzed strain, and wild-type strain. These results indicated that
      the flagella and the flagellar motility inhibited the cell detachment from the
      glass substratum. Furthermore, a large external force would likely be required to
      inhibit the microbial adhesion in the early stage of the biofilm formation. 

PMID- 25956748
TI  - Esophageal neoplasia arising from subsquamous buried glands after an apparently
      successful photodynamic therapy or radiofrequency ablation for Barrett's
      associated neoplasia.
AB  - OBJECTIVE: Photodynamic therapy (PDT) and radiofrequency ablation (RFA) are
      effective non-surgical options for the treatment of Barrett's esophagus (BE)
      associated neoplasia. Development of subsquamous intestinal metaplasia after
      successful PDT and/or RFA is a recognized phenomenon; however, the occurrence of
      neoplasia arising from buried glands is a rare complication. METHODS: This is a
      prospective case series of patients treated with PDT and/or RFA from 1999 to 2014
      at University College London Hospital for neoplasia associated with BE, whose
      outcomes were analyzed retrospectively. Prior to any ablative therapy any visible
      nodularity was removed with endoscopic mucosal resection (EMR). After successful
      PDT and/or HALO RFA treatment, defined as a complete reversal of dysplasia and
      metaplasia, patients underwent endoscopic follow up using the Seattle protocol.
      RESULTS: A total of 288 patients were treated, 91 with PDT between 1999 and 2010,
      173 with RFA between 2007 and 2014, and 24 with both PDT and RFA for neoplasia
      associated with BE. Subsquamous neoplasia occurred in seven patients (7/288, 2%).
      The first patient developed subsquamous invasive adenocarcinoma and underwent
      curative surgery. Another five patients with subsquamous neoplasia (either high
      grade dysplasia or intramucosal cancer) were treated successfully with EMR. The
      final patient developed subsquamous invasive esophagogastric junctional
      adenocarcinoma with liver metastases. CONCLUSION: Development of subsquamous
      neoplasia after an apparently successful PDT and/or RFA is a rare but recognized
      complication. Clinicians should be aware of this phenomenon and have a low
      threshold for performing an EMR. Thorough surveillance following successful PDT
      and/or RFA ensuring high-quality endoscopy is required.

PMID- 25956747
TI  - Short loop length and high thermal stability determine genomic instability
      induced by G-quadruplex-forming minisatellites.
AB  - G-quadruplexes (G4) are polymorphic four-stranded structures formed by certain G
      rich nucleic acids, with various biological roles. However, structural features
      dictating their formation and/or function in vivo are unknown. In S. cerevisiae,
      the pathological persistency of G4 within the CEB1 minisatellite induces its
      rearrangement during leading-strand replication. We now show that several other
      G4-forming sequences remain stable. Extensive mutagenesis of the CEB25
      minisatellite motif reveals that only variants with very short (<= 4 nt) G4 loops
      preferentially containing pyrimidine bases trigger genomic instability. Parallel
      biophysical analyses demonstrate that shortening loop length does not change the
      monomorphic G4 structure of CEB25 variants but drastically increases its thermal
      stability, in correlation with the in vivo instability. Finally, bioinformatics
      analyses reveal that the threat for genomic stability posed by G4 bearing short
      pyrimidine loops is conserved in C. elegans and humans. This work provides a
      framework explanation for the heterogeneous instability behavior of G4-forming
      sequences in vivo, highlights the importance of structure thermal stability, and
      questions the prevailing assumption that G4 structures with short or longer loops
      are as likely to form in vivo.

PMID- 25956749
TI  - [Anticoagulation in the aged patient with atrial fibrillation: What are
      prescribing cardiologists, geriatricians and general practitioners?].
AB  - OBJECTIVE: To assess prescribing of anticoagulants in atrial fibrillation (AF) in
      the elderly, both a quantitative point of view (rate of anticoagulation) and
      qualitative (type of anticoagulation). Determinants of prescribing and non
      prescribing were also analysed. METHODS: Prospective survey of practice, based on
      one clinical case and questionnaire conducted in 60 practitioners (20
      cardiologists [C], 20 geriatricians [G] and 20 general practitioners [GP]).
      RESULTS: In reading the clinical case, 88.3% of physicians would have initiated a
      treatment; three types of treatments would have been chosen: AVK (68.3%), ODA
      (20.0%) and platelet antiaggregant (11.7%). Criteria taken into account to
      initiate anticoagulation varied according to the specialty. Cardiologists
      considered more the age criteria (C: 95.0%, G: 75.0%, MG: 60.0%; P<0.05),
      diabetes (C: 90.0%, G: 60.0%, MG: 55.0%; P<0.05), hypertension (C: 85.0%, G:
      55.0%, MG: 60.0%; P<0.05) and female gender (C: 80.0%, G: 35.0%, MG: 25.0%;
      P<0.05). The quality of renal function was however a more secondary criteria (C:
      15.0%, G: 5.0%, MG: 0.0%; P<0.05). General practitioners considered most
      frequently the presence of underlying heart disease (C: 35.0%, G: 5.0%, MG:
      45.0%; P<0.05) as well as usual cardiovascular risk factors (overweight,
      dyslipidaemia; P<0.05). Risk of bleeding, however, was observed by 76.7% of
      physicians in the clinical situation presented (C: 70.0%, G: 75.0%, MG: 85.0%;
      P<0.05). CONCLUSION: This survey confirms that the FA remains under
      anticoagulated in the elderly and the barriers to the prescription of oral
      anticoagulation are often without rational basis.

PMID- 25956752
TI  - Effects of religiosity and spirituality on the treatment response in patients
      with depressive disorders.
AB  - BACKGROUND: Few studies have investigated the roles of religiosity and
      spirituality in predicting treatment response among psychiatric patients with
      depressive disorders. METHODS: In total, 232 outpatients with depressive
      disorders completed measurements of psychological symptoms, religiosity, and
      spirituality at baseline. A response was defined as Clinical Global Impression
      Improvement scale (CGI-I) score of 1 or 2 at the last visit during a 6-month
      treatment period. Univariate analyses and logistic regression analysis were used
      to identify predictors of treatment response. RESULTS: In univariate analyses,
      treatment response was associated with marital status, longer treatment duration,
      less severe baseline symptoms, higher personal importance of religion, and higher
      spirituality. In logistic regression analysis, subjective important
      considerations for religion and spirituality were significantly related with
      treatment response after controlling for marital status, treatment duration, and
      baseline symptom severity. Of these variables, spirituality remained a
      significant predictor in the final model. CONCLUSIONS: These findings suggest
      that higher spirituality may independently contribute to favorable treatment
      responses among depressed patients in addition to other demographic and clinical
      factors.

PMID- 25956751
TI  - Age at onset of DSM-IV pathological gambling in a non-treatment sample: Early-
      versus later-onset.
AB  - BACKGROUND: Pathological gambling (PG) is a prevalent and impairing public health
      problem. In this study we assessed age at onset in men and women with PG and
      compared the demographic and clinical picture of early- vs. later-onset
      individuals. We also compared age at onset in PG subjects and their first-degree
      relatives with PG. METHOD: Subjects with DSM-IV PG were recruited during the
      conduct of two non-treatment clinical studies. Subjects were evaluated with
      structured interviews and validated questionnaires. Early-onset was defined as PG
      starting prior to age 33years. RESULTS: Age at onset of PG in the 255 subjects
      ranged from 8 to 80years with a mean (SD) of 34.0 (15.3) years. Men had an
      earlier onset than women. 84% of all subjects with PG had developed the disorder
      by age 50years. Early-onset subjects were more likely to be male, to prefer
      action games, and to have substance use disorders, antisocial personality
      disorder, attention deficit/hyperactivity disorder, trait impulsiveness, and
      social anxiety disorder. Later-onset was more common in women and was associated
      with a preference for slots and a history of sexual abuse. CONCLUSIONS: Age at
      onset of PG is bimodal and differs for men and women. Early-onset PG and later
      onset PG have important demographic and clinical differences. The implications of
      the findings are discussed.

PMID- 25956750
TI  - Randomized phase III clinical trial comparing the combination of capecitabine and
      oxaliplatin (CAPOX) with the combination of 5-fluorouracil, leucovorin and
      oxaliplatin (modified FOLFOX6) as adjuvant therapy in patients with operated high
      risk stage II or stage III colorectal cancer.
AB  - BACKGROUND: The aim of the trial was to compare two active adjuvant chemotherapy
      regimens in patients with early stage colorectal cancer (CRC). METHODS: Patients
      were assigned to oxaliplatin, leucovorin and 5-FU for 12 cycles (group A,
      FOLFOX6) or oxaliplatin and capecitabine for eight cycles (group B, CAPOX).
      Primary endpoint was disease-free survival (DFS). Tumors were classified as
      mismatch repair proficient (pMMR) or deficient (dMMR) according to MLH1, PMS2,
      MSH2 and MSH6 protein expression. KRAS exon two and BRAF V600E mutational status
      were also assessed. RESULTS: Between 2005 and 2008, 441 patients were enrolled,
      with 408 patients being eligible. After a median follow-up of 74.7 months, 3-year
      DFS was 79.8 % (95 % CI 76.5-83.4) in the FOLFOX group and 79.5 % (95 % CI 75.9
      83.1) in the CAPOX group (p = 0.78). Three-year OS was 87.2 % (95 % CI 84.1-91.1)
      in the FOLFOX and 86.9 % (95 % CI 83.4-89.9) in the CAPOX group (p = 0.84). Among
      306 available tumors, 11.0 % were dMMR, 34.0 % KRAS mutant and 4.9 % BRAF mutant.
      Multivariate analysis showed that primary site in the left colon, earlier TNM
      stage and the presence of anemia at diagnosis were associated with better DFS and
      overall survival (OS), while grade one-two tumors were associated with better OS.
      Finally, a statistically significant interaction was detected between the primary
      site and MMR status (p = 0.010), while KRAS mutated tumors were associated with
      shorter DFS. However, the sample was too small for safe conclusions. CONCLUSIONS:
      No significant differences were observed in the efficacy of FOLFOX versus CAPOX
      as adjuvant treatment in high-risk stage II or stage III CRC patients, but
      definitive conclusions cannot be drawn because of the small sample size. TRIAL
      REGISTRATION: ANZCTR 12610000509066 . Date of Registration: June 21, 2010.

PMID- 25956753
TI  - Changes in malondialdehyde and C-reactive protein concentrations after lifestyle
      modification are related to different metabolic syndrome-associated
      pathophysiological processes.
AB  - AIMS: Metabolic syndrome (MetS) is often accompanied by pro-oxidative and pro
      inflammatory processes. Lifestyle modification (LiSM) may act as primary
      treatment for these processes. This study aimed to elucidate influencing factors
      on changes of malondialdehyde (MDA) and C-reactive protein (CRP) concentrations
      after a LiSM intervention. METHODS: Sixty subjects (53 yrs, 84% women) clinically
      approved to attend a 20 weeks LiSM-program were submitted to weekly nutritional
      counseling and physical activities combining aerobic (3 times/week) and
      resistance (2 times/week) exercises. Before and after intervention they were
      assessed for anthropometric, clinical, cardiorespiratory fitness test (CRF) and
      laboratory markers. Statistical analyses performed were multiple regression
      analysis and backward stepwise with p<0.05 and R(2) as influence index. RESULTS:
      LiSM was responsible for elevations in CRF, healthy eating index (HEI), total
      plasma antioxidant capacity (TAP) and HDL-C along with reductions in waist
      circumference measures and MetS (47-40%) prevalence. MDA and CRP did not change
      after LiSM, however, we observed that MDA concentrations were positively
      influenced (R(2)=0.35) by fasting blood glucose (beta=0.64) and HOMA-IR
      (beta=0.58) whereas CRP concentrations were by plasma gamma-glutamyltransferase
      activity (beta=0.54; R(2)=0.29). CONCLUSIONS: Pro-oxidant and pro-inflammatory
      states of MetS can be attenuated after lifestyle modification if glucose
      metabolism homeostasis were recovered and if liver inflammation were reduced,
      respectively.

PMID- 25956754
TI  - Sutureless 3f Enable valve implantation concomitant with mitral valve surgery.
AB  - OBJECTIVE: Interest in aortic sutureless bioprostheses is growing. Here, we
      evaluate the feasibility of performing aortic sutureless valve replacement
      concomitant with mitral valve surgery using the 3f Enable prosthesis. METHODS: Of
      the 198 3f Enable(r) valve implantation procedures carried out in our unit
      between March 2011 and October 2014, 15 were performed concomitant with mitral
      valve surgery (8 bioprosthetic replacements and 7 annuloplasties). RESULTS: The
      mean age and logistic EuroSCORE were 76 +/- 6 years and 10.2 +/- 4.8,
      respectively. The procedural success rate of aortic sutureless valve implantation
      was 100%. Mean cross-clamping and cardiopulmonary bypass times were 113.9 +/- 35
      and 150- +/- 43 min, respectively. No reclamping in response to a sutureless
      paravalvular leakage (PVL) was needed. One grade 1 leak was observed at the time
      of discharge. There was no perioperative mortality. Pacemaker implantation was
      required in 1 case (6.6%). Initial follow-up (median = 8 months, range 1-6)
      showed no new aortic PVL; mean and peak transprosthetic gradients and the orifice
      area were 11.1 +/- 2.5 and 18.4 +/- 4.9 mmHg and 1.7 +/- 0.4 cm(2), respectively.
      One grade 2 and two grade 1 mitral valve leaks were detected following
      annuloplasty. CONCLUSIONS: 3f Enable(r) sutureless valve implantation combined
      with mitral valve surgery appears feasible and the results presented here are
      encouraging. This procedure has the potential to simplify surgery in a cohort of
      high-risk patients for whom transcatheter aortic valve replacement is not an
      effective option. Larger studies should be conducted to confirm these
      observations.

PMID- 25956755
TI  - Aortic atresia with interrupted aortic arch: a combination incompatible with
      life?

PMID- 25956756
TI  - Mini-partial heart autotransplantation: a different way to perform the Cox-maze
      III.
AB  - The Cox-maze III procedure is the gold standard for the surgical treatment of
      atrial fibrillation. Because of its complexity, this procedure has not been
      widely accepted by cardiac surgeons. We describe a technique that allows one to
      work on the mitral valve while more safely performing the standard 'cut-and-sew'
      Cox-maze III procedure at the same time. 

PMID- 25956758
TI  - The panic disorder screener (PADIS): Development of an accurate and brief
      population screening tool.
AB  - The Panic Disorder Screener (PADIS) was developed as a new screener to identify
      panic disorder in the community and to assess severity of symptoms. The PADIS was
      developed to fill a gap in existing screening measures, as there are no brief
      panic screeners available that assess severity. The current study aimed to test
      the performance of the screener relative to the Patient Health Questionnaire
      panic scale (PHQ-panic). The 4-item PADIS was administered to 12,336 young
      Australian adults, together with the PHQ-panic. A subsample of 1674 participants
      also completed a phone-based clinical interview to determine whether they met DSM
      IV criteria for panic disorder. The PADIS (77% sensitivity, 84% specificity) had
      higher sensitivity for identifying panic disorder based on clinical criteria than
      the PHQ-panic (57% sensitivity, 91% specificity), although with reduced
      specificity. Administration of the PADIS required a mean of 1.9 items, compared
      to 4.7 items for the PHQ-panic. Each one-point increase in PADIS score was
      associated with 69% increased odds of meeting clinical criteria for panic
      disorder. The PADIS was found to be a valid, reliable and brief panic screener
      that is freely available for use in research and clinical settings. 

PMID- 25956757
TI  - Urine podocyte mRNAs mark disease activity in IgA nephropathy.
AB  - BACKGROUND: Podocyte depletion is a major mechanism driving glomerulosclerosis.
      We and others have previously projected from model systems that podocyte-specific
      mRNAs in the urine pellet might serve as glomerular disease markers. We evaluated
      IgA nephropathy (IgAN) to test this concept. METHODS: From 2009 to 2013, early
      morning voided urine samples and kidney biopsies from IgAN patients (n = 67) were
      evaluated in comparison with urine samples from healthy age-matched volunteers (n
      = 28). Urine podocyte (podocin) mRNA expressed in relation to either urine
      creatinine concentration or a kidney tubular marker (aquaporin 2) was tested as
      markers. RESULTS: Urine podocyte mRNAs were correlated with the severity of
      active glomerular lesions (segmental glomerulosclerosis and acute extracapillary
      proliferation), but not with non-glomerular lesions (tubular atrophy/interstitial
      fibrosis) or with clinical parameters of kidney injury (serum creatinine and
      estimated glomerular filtration rate), or with degree of accumulated podocyte
      loss at the time of biopsy. In contrast, proteinuria correlated with all
      histological and clinical markers. Glomerular tuft podocyte nuclear density (a
      measure of cumulative podocyte loss) correlated with tubular atrophy/interstitial
      fibrosis, estimated-glomerular filtration rate and proteinuria, but not with
      urine podocyte markers. In a subset of the IgA cohort (n = 19, median follow-up
      period = 37 months), urine podocyte mRNAs were significantly decreased after
      treatment, in contrast to proteinuria which was not significantly changed.
      CONCLUSIONS: Urine podocyte mRNAs reflect active glomerular injury at a given
      point in time, and therefore provide both different and additional clinical
      information that can complement proteinuria in the IgAN decision-making paradigm.

PMID- 25956759
TI  - Screening instruments for a population of older adults: The 10-item Kessler
      Psychological Distress Scale (K10) and the 7-item Generalized Anxiety Disorder
      Scale (GAD-7).
AB  - Screening tools that appropriately detect older adults' mental disorders are of
      great public health importance. The present study aimed to establish cutoff
      scores for the 10-item Kessler Psychological Distress (K10) and the 7-item
      Generalized Anxiety Disorder (GAD-7) scales when screening for depression and
      anxiety. We used data from participants (n = 1811) in the Enquete sur la Sante
      des Aines-Service study. Depression and anxiety were measured using DSM-V and DSM
      IV criteria. Receiver operating characteristic (ROC) curve analysis provided an
      area under the curve (AUC) of 0.767 and 0.833 for minor and for major depression
      when using K10. A cutoff of 19 was found to balance sensitivity (0.794) and
      specificity (0.664) for minor depression, whereas a cutoff of 23 was found to
      balance sensitivity (0.692) and specificity (0.811) for major depression. When
      screening for an anxiety with GAD-7, ROC analysis yielded an AUC of 0.695; a
      cutoff of 5 was found to balance sensitivity (0.709) and specificity (0.568). No
      significant differences were found between subgroups of age and gender. Both K10
      and GAD-7 were able to discriminate between cases and non-cases when screening
      for depression and anxiety in an older adult population of primary care service
      users.

PMID- 25956760
TI  - Could autonomous motivation hold the key to successfully implementing lifestyle
      changes in affective disorders? A multicentre cross sectional study.
AB  - There is a need for theoretically-based research on the motivational processes
      linked to the adoption and maintenance of an active lifestyle in people with
      affective disorders. Within the Self-Determination Theory (SDT) framework, we
      investigated the SDT tenets in people with major depressive disorder or bipolar
      disorder by examining the factor structure of the Behavioural Regulation in
      Exercise Questionnaire-2 (BREQ-2) and by investigating associations between
      motivation, the Positive and Negative Affect Scale (PANAS) and International
      Physical Activity Questionnaire (IPAQ) scores. A total of 165 patients (105 ?)
      (45.6 +/- 14.2 years) agreed to participate. An exploratory factor analysis
      demonstrated sufficient convergence with the original factor for amotivation, and
      external and introjected regulation. The items of identified and intrinsic
      regulation loaded on the same factor, which was labelled autonomous regulation.
      Significant correlations were found between the total IPAQ score and the
      subscales amotivation, external regulation, introjected regulation and autonomous
      regulation. The relative autonomy index (RAI) was associated with the PANAS
      scores. Differences in RAI were found between physically inactive and active
      participants. Our results suggest that in people with affective disorders the
      level of autonomous motivation may play an important role in the adoption and
      maintenance of health promoting behaviours.

PMID- 25956762
TI  - Access all areas? An area-level analysis of accessibility to general practice and
      community pharmacy services in England by urbanity and social deprivation.
AB  - OBJECTIVES: (1) To determine the percentage of the population in England that has
      access to a general practitioner (GP) premises within a 20 min walk (the
      accessibility); (2) explore the relationship between the walking distance to a GP
      premises and urbanity and social deprivation and (3) compare accessibility of a
      GP premises to that of a community pharmacy--and how this may vary by urbanity
      and social deprivation. DESIGN: This area-level analysis spatial study used
      postcodes for all GP premises and community pharmacies in England. Each postcode
      was assigned to a population lookup table and Lower Super Output Area (LSOA). The
      LSOA was then matched to urbanity (urban, town and fringe, or village, hamlet and
      isolated dwellings) and deprivation decile (using the Index of Multiple
      Deprivation score 2010). PRIMARY OUTCOME MEASURE: Living within a 20 min walk of
      a GP premises. RESULTS: Overall, 84.8% of the population is estimated to live
      within a 20 min walk of a GP premises: 81.2% in the most affluent areas, 98.2% in
      the most deprived areas, 94.2% in urban and 19.4% in rural areas. This is
      consistently lower when compared with the population living within a 20 min walk
      of a community pharmacy. CONCLUSIONS: Our study shows that the vast majority of
      the population live within a 20 min walk of a GP premises, with higher
      proportions in the most deprived areas--a positive primary care law. However,
      more people live within a 20 min walk of a community pharmacy compared with a GP
      premises, and this potentially has implications for the commissioning of future
      services from these healthcare providers in England.

PMID- 25956761
TI  - Deviant white matter structure in adults with attention-deficit/hyperactivity
      disorder points to aberrant myelination and affects neuropsychological
      performance.
AB  - Attention-deficit/hyperactivity disorder (ADHD) in childhood is characterized by
      gray and white matter abnormalities in several brain areas. Considerably less is
      known about white matter microstructure in adults with ADHD and its relation with
      clinical symptoms and cognitive performance. In 107 adult ADHD patients and 109
      gender-, age- and IQ-matched controls, we used diffusion tensor imaging (DTI)
      with tract-based spatial statistics (TBSS) to investigate whole-skeleton changes
      of fractional anisotropy (FA) and mean, axial, and radial diffusivity (MD, AD,
      RD). Additionally, we studied the relation of FA and MD values with symptom
      severity and cognitive performance on tasks measuring working memory, attention,
      inhibition, and delay discounting. In comparison to controls, participants with
      ADHD showed reduced FA in corpus callosum, bilateral corona radiata, and thalamic
      radiation. Higher MD and RD were found in overlapping and even more widespread
      areas in both hemispheres, also encompassing internal and external capsule,
      sagittal stratum, fornix, and superior lateral fasciculus. Values of FA and MD
      were not associated with symptom severity. However, within some white matter
      clusters that distinguished patients from controls, worse inhibition performance
      was associated with reduced FA and more impulsive decision making was associated
      with increased MD. This study shows widespread differences in white matter
      integrity between adults with persistent ADHD and healthy individuals. Changes in
      RD suggest aberrant myelination as a pathophysiological factor in persistent
      ADHD. The microstructural differences in adult ADHD may contribute to poor
      inhibition and greater impulsivity but appear to be independent of disease
      severity. 

PMID- 25956763
TI  - Use of Hybridization Chain Reaction-Fluorescent In Situ Hybridization To Track
      Gene Expression by Both Partners during Initiation of Symbiosis.
AB  - The establishment of a productive symbiosis between Euprymna scolopes, the
      Hawaiian bobtail squid, and its luminous bacterial symbiont, Vibrio fischeri, is
      mediated by transcriptional changes in both partners. A key challenge to
      unraveling the steps required to successfully initiate this and many other
      symbiotic associations is characterization of the timing and location of these
      changes. We report on the adaptation of hybridization chain reaction-fluorescent
      in situ hybridization (HCR-FISH) to simultaneously probe the spatiotemporal
      regulation of targeted genes in both E. scolopes and V. fischeri. This method
      revealed localized, transcriptionally coregulated epithelial cells within the
      light organ that responded directly to the presence of bacterial cells while, at
      the same time, provided a sensitive means to directly show regulated gene
      expression within the symbiont population. Thus, HCR-FISH provides a new approach
      for characterizing habitat transition in bacteria and for discovering host tissue
      responses to colonization. 

PMID- 25956764
TI  - Depth-Dependent Survival of Escherichia coli and Enterococci in Soil after Manure
      Application and Simulated Rainfall.
AB  - Once released, manure-borne bacteria can enter runoff via interaction with the
      thin mixing layer near the soil surface. The objectives of this work were to
      document temporal changes in profile distributions of manure-borne Escherichia
      coli and enterococci in the near-surface soil layers after simulated rainfalls
      and to examine differences in survival of the two fecal indicator bacteria.
      Rainfall simulations were performed in triplicate on soil-filled boxes with grass
      cover and solid manure application for 1 h with rainfall depths of 30, 60, and 90
      mm. Soil samples were collected weekly from depth ranges of 0 to 1, 1 to 2, 2 to
      5, and 5 to 10 cm for 1 month. Rainfall intensity was found to have a significant
      impact on the initial concentrations of fecal indicator bacteria in the soil.
      While total numbers of enterococci rapidly declined over time, E. coli
      populations experienced initial growth with concentration increases of 4, 10, and
      25 times the initial levels at rainfall treatment depths of 30, 60, and 90 mm,
      respectively. E. coli populations grew to the approximately the same level in all
      treatments. The 0- to 1-cm layer contained more indicator bacteria than the
      layers beneath it, and survival of indicator bacteria was better in this layer,
      with decimation times between 12 and 18 days after the first week of growth. The
      proportion of bacteria in the 0- to 1-cm layer grew with time as the total number
      of bacteria in the 0- to 10-cm layer declined. The results of this work indicate
      the need to revisit the bacterial survival patterns that are assumed in water
      quality models. 

PMID- 25956765
TI  - Enterocin F4-9, a Novel O-Linked Glycosylated Bacteriocin.
AB  - Enterococcus faecalis F4-9 isolated from Egyptian salted-fermented fish produces
      a novel bacteriocin, termed enterocin F4-9. Enterocin F4-9 was purified from the
      culture supernatant by three steps, and its molecular mass was determined to be
      5,516.6 Da by mass spectrometry. Amino acid and DNA sequencing showed that the
      propeptide consists of 67 amino acid residues, with a leader peptide containing a
      double glycine cleavage site to produce a 47-amino-acid mature peptide. Enterocin
      F4-9 is modified by two molecules of N-acetylglucosamine beta-O-linked to Ser37
      and Thr46. The O-linked N-acetylglucosamine moieties are essential for the
      antimicrobial activity of enterocin F4-9. Further analysis of the enterocin F4-9
      gene cluster identified enfC, which has high sequence similarity to a
      glycosyltransferase. The antimicrobial activity of enterocin F4-9 covered a
      limited range of bacteria, including, interestingly, a Gram-negative strain,
      Escherichia coli JM109. Enterocin F4-9 is sensitive to protease, active at a wide
      pH range, and moderately resistant to heat. 

PMID- 25956766
TI  - Role of Extracellular Structures of Escherichia coli O157:H7 in Initial
      Attachment to Biotic and Abiotic Surfaces.
AB  - Infection by human pathogens through the consumption of fresh, minimally
      processed produce and solid plant-derived foods is a major concern of the U.S.
      and global food industries and of public health services. Enterohemorrhagic
      Escherichia coli O157:H7 is a frequent and potent foodborne pathogen that causes
      severe disease in humans. Biofilms formed by E. coli O157:H7 facilitate cross
      contamination by sheltering pathogens and protecting them from cleaning and
      sanitation operations. The objective of this research was to determine the role
      that several surface structures of E. coli O157:H7 play in adherence to biotic
      and abiotic surfaces. A set of isogenic deletion mutants lacking major surface
      structures was generated. The mutant strains were inoculated onto fresh spinach
      and glass surfaces, and their capability to adhere was assessed by adherence
      assays and fluorescence microscopy methods. Our results showed that filament
      deficient mutants bound to the spinach leaves and glass surfaces less strongly
      than the wild-type strain did. We mimicked the switch to the external environment
      during which bacteria leave the host organism and adapt to lower ambient
      temperatures of cultivation or food processing-by decreasing the temperature from
      37 degrees C to 25 degrees C and 4 degrees C. We concluded that flagella and some
      other cell surface proteins are important factors in the process of initial
      attachment and in the establishment of biofilms. A better understanding of the
      specific roles of these structures in early stages of biofilm formation can help
      to prevent cross-contaminations and foodborne disease outbreaks. 

PMID- 25956767
TI  - Energy Conservation Model Based on Genomic and Experimental Analyses of a Carbon
      Monoxide-Utilizing, Butyrate-Forming Acetogen, Eubacterium limosum KIST612.
AB  - Eubacterium limosum KIST612 is one of the few acetogens that can produce butyrate
      from carbon monoxide. We have used a genome-guided analysis to delineate the path
      of butyrate formation, the enzymes involved, and the potential coupling to ATP
      synthesis. Oxidation of CO is catalyzed by the acetyl-coenzyme A (CoA)
      synthase/CO dehydrogenase and coupled to the reduction of ferredoxin. Oxidation
      of reduced ferredoxin is catalyzed by the Rnf complex and Na(+) dependent.
      Consistent with the finding of a Na(+)-dependent Rnf complex is the presence of a
      conserved Na(+)-binding motif in the c subunit of the ATP synthase. Butyrate
      formation is from acetyl-CoA via acetoacetyl-CoA, hydroxybutyryl-CoA, crotonyl
      CoA, and butyryl-CoA and is consistent with the finding of a gene cluster that
      encodes the enzymes for this pathway. The activity of the butyryl-CoA
      dehydrogenase was demonstrated. Reduction of crotonyl-CoA to butyryl-CoA with
      NADH as the reductant was coupled to reduction of ferredoxin. We postulate that
      the butyryl-CoA dehydrogenase uses flavin-based electron bifurcation to reduce
      ferredoxin, which is consistent with the finding of etfA and etfB genes next to
      it. The overall ATP yield was calculated and is significantly higher than the one
      obtained with H2 + CO2. The energetic benefit may be one reason that butyrate is
      formed only from CO but not from H2 + CO2. 

PMID- 25956768
TI  - The Host Genotype and Environment Affect Strain Types of Bifidobacterium longum
      subsp. longum Inhabiting the Intestinal Tracts of Twins.
AB  - To investigate the influences of host genotype and environment on Bifidobacterium
      longum subsp. longum inhabiting human intestines at the strain level, six pairs
      of twins, divided into two groups (children and adults), were recruited. Each
      group consisted of two monozygotic (MZ) twin pairs and one dizygotic (DZ) twin
      pair. Child twins had been living together from birth, while adult twins had been
      living separately for 5 to 10 years. A total of 345 B. longum subsp. longum
      isolates obtained from 60 fecal samples from these twins were analyzed by
      multilocus sequence typing (MLST), and 35 sequence types (STs) were finally
      acquired. Comparison of strains within and between the twin pairs showed that no
      strains with identical STs were observed between unrelated individuals or within
      adult DZ twin pairs. Eight STs were found to be monophyletic, existing within MZ
      twins and child DZ twins. The similarity of strain types within child cotwins was
      significantly higher than that within adult cotwins, which indicated that
      environment was one of the important determinants in B. longum subsp. longum
      strain types inhabiting human intestines. However, although these differences
      between MZ and DZ twins were observed, it is still difficult to reach an exact
      conclusion about the impact of host genotype. This is mainly because of the
      limited number of subjects tested in the present study and the lack of strain
      types tracing in the same twin pairs from birth until adulthood. 

PMID- 25956769
TI  - Intracellular Accumulation of Glycine in Polyphosphate-Accumulating Organisms in
      Activated Sludge, a Novel Storage Mechanism under Dynamic Anaerobic-Aerobic
      Conditions.
AB  - Dynamic anaerobic-aerobic feast-famine conditions are applied to wastewater
      treatment plants to select polyphosphate-accumulating organisms to carry out
      enhanced biological phosphorus removal. Acetate is a well-known substrate to
      stimulate this process, and here we show that different amino acids also are
      suitable substrates, with glycine as the most promising. (13)C-labeled glycine
      and nuclear magnetic resonance (NMR) were applied to investigate uptake and
      potential storage products when activated sludge was fed with glycine under
      anaerobic conditions. Glycine was consumed by the biomass, and the majority was
      stored intracellularly as free glycine and fermentation products. Subsequently,
      in the aerobic phase without addition of external substrate, the stored glycine
      was consumed. The uptake of glycine and oxidation of intracellular metabolites
      took place along with a release and uptake of orthophosphate, respectively.
      Fluorescence in situ hybridization combined with microautoradiography using (3)H
      labeled glycine revealed uncultured actinobacterial Tetrasphaera as a dominant
      glycine consumer. Experiments with Tetrasphaera elongata as representative of
      uncultured Tetrasphaera showed that under anaerobic conditions it was able to
      take up labeled glycine and accumulate this and other labeled metabolites to an
      intracellular concentration of approximately 4 mM. All components were consumed
      under subsequent aerobic conditions. Intracellular accumulation of amino acids
      seems to be a novel storage strategy for polyphosphate-accumulating bacteria
      under dynamic anaerobic-aerobic feast-famine conditions. 

PMID- 25956770
TI  - Semiquantitative Performance and Mechanism Evaluation of Carbon Nanomaterials as
      Cathode Coatings for Microbial Fouling Reduction.
AB  - In this study, we examine bacterial attachment and survival on a titanium (Ti)
      cathode coated with various carbon nanomaterials (CNM): pristine carbon nanotubes
      (CNT), oxidized carbon nanotubes (O-CNT), oxidized-annealed carbon nanotubes (OA
      CNT), carbon black (CB), and reduced graphene oxide (rGO). The carbon
      nanomaterials were dispersed in an isopropyl alcohol-Nafion solution and were
      then used to dip-coat a Ti substrate. Pseudomonas fluorescens was selected as the
      representative bacterium for environmental biofouling. Experiments in the absence
      of an electric potential indicate that increased nanoscale surface roughness and
      decreased hydrophobicity of the CNM coating decreased bacterial adhesion. The
      loss of bacterial viability on the noncharged CNM coatings ranged from 22% for CB
      to 67% for OA-CNT and was dependent on the CNM dimensions and surface chemistry.
      For electrochemical experiments, the total density and percentage of inactivation
      of the adherent bacteria were analyzed semiquantitatively as functions of
      electrode potential, current density, and hydrogen peroxide generation. Electrode
      potential and hydrogen peroxide generation were the dominant factors with regard
      to short-term (3-h) bacterial attachment and inactivation, respectively. Extended
      time electrochemical experiments (12 h) indicated that in all cases, the density
      of total deposited bacteria increased almost linearly with time and that the rate
      of bacterial adhesion was decreased 8- to 10-fold when an electric potential was
      applied. In summary, this study provides a fundamental rationale for the
      selection of CNM as cathode coatings and electric potential to reduce microbial
      fouling. 

PMID- 25956771
TI  - Optimization of Methanotrophic Growth and Production of Poly(3-Hydroxybutyrate)
      in a High-Throughput Microbioreactor System.
AB  - Production of poly(3-hydroxybutyrate) (P3HB) from methane has economic and
      environmental advantages over production by agricultural feedstock.
      Identification of high-productivity strains and optimal growth conditions is
      critical to efficient conversion of methane to polymer. Current culture
      conditions, including serum bottles, shake flasks, and agar plates, are labor
      intensive and therefore insufficient for systematic screening and isolation. Gas
      chromatography, the standard method for analysis of P3HB content in bacterial
      biomass, is also incompatible with high-throughput screening. Growth in aerated
      microtiter plates coupled with a 96-well Nile red flow-cytometric assay creates
      an integrated microbioreactor system for high-throughput growth and analysis of
      P3HB-producing methanotrophic cultures, eliminating the need for individual
      manipulation of experimental replicates. This system was tested in practice to
      conduct medium optimization for P3HB production in pure cultures of Methylocystis
      parvus OBBP. Optimization gave insight into unexpected interactions: for example,
      low calcium concentrations significantly enhanced P3HB production under nitrogen
      limited conditions. Optimization of calcium and copper concentrations in the
      growth medium increased final P3HB content from 18.1% to 49.4% and P3HB
      concentration from 0.69 g/liter to 3.43 g/liter while reducing doubling time from
      10.6 h to 8.6 h. The ability to culture and analyze thousands of replicates with
      high mass transfer in completely mixed culture promises to streamline medium
      optimization and allow the detection and isolation of highly productive strains.
      Applications for this system are numerous, encompassing analysis of biofuels and
      other lipid inclusions, as well as analysis of heterotrophic and photosynthetic
      systems. 

PMID- 25956772
TI  - Stoichiometric Assembly of the Cellulosome Generates Maximum Synergy for the
      Degradation of Crystalline Cellulose, as Revealed by In Vitro Reconstitution of
      the Clostridium thermocellum Cellulosome.
AB  - The cellulosome is a supramolecular multienzyme complex formed by species
      specific interactions between the cohesin modules of scaffoldin proteins and the
      dockerin modules of a wide variety of polysaccharide-degrading enzymes.
      Cellulosomal enzymes bound to the scaffoldin protein act synergistically to
      degrade crystalline cellulose. However, there have been few attempts to
      reconstitute intact cellulosomes due to the difficulty of heterologously
      expressing full-length scaffoldin proteins. We describe the synthesis of a full
      length scaffoldin protein containing nine cohesin modules, CipA; its deletion
      derivative containing two cohesin modules, DeltaCipA; and three major
      cellulosomal cellulases, Cel48S, Cel8A, and Cel9K, of the Clostridium
      thermocellum cellulosome. The proteins were synthesized using a wheat germ cell
      free protein synthesis system, and the purified proteins were used to
      reconstitute cellulosomes. Analysis of the cellulosome assembly using size
      exclusion chromatography suggested that the dockerin module of the enzymes
      stoichiometrically bound to the cohesin modules of the scaffoldin protein. The
      activity profile of the reconstituted cellulosomes indicated that cellulosomes
      assembled at a CipA/enzyme molar ratio of 1/9 (cohesin/dockerin = 1/1) and showed
      maximum synergy (4-fold synergy) for the degradation of crystalline substrate and
      ~2.4-fold-higher synergy for its degradation than minicellulosomes assembled at a
      DeltaCipA/enzyme molar ratio of 1/2 (cohesin/dockerin = 1/1). These results
      suggest that the binding of more enzyme molecules on a single scaffoldin protein
      results in higher synergy for the degradation of crystalline cellulose and that
      the stoichiometric assembly of the cellulosome, without excess or insufficient
      enzyme, is crucial for generating maximum synergy for the degradation of
      crystalline cellulose. 

PMID- 25956773
TI  - Effects of Abiotic and Biotic Stresses on the Internalization and Dissemination
      of Human Norovirus Surrogates in Growing Romaine Lettuce.
AB  - Human norovirus (NoV) is the major causative agent of fresh-produce-related
      outbreaks of gastroenteritis; however, the ecology and persistence of human NoV
      in produce systems are poorly understood. In this study, the effects of abiotic
      and biotic stresses on the internalization and dissemination of two human NoV
      surrogates (murine norovirus 1 [MNV-1] and Tulane virus [TV]) in romaine lettuce
      were determined. To induce abiotic stress, romaine lettuce was grown under
      drought and flood conditions that mimic extreme weather events, followed by
      inoculation of soil with MNV-1 or TV. Independently, lettuce plants were infected
      with lettuce mosaic virus (LMV) to induce biotic stress, followed by inoculation
      with TV. Plants were grown for 14 days, and viral titers in harvested tissues
      were determined by plaque assays. It was found that drought stress significantly
      decreased the rates of both MNV-1 and TV internalization and dissemination. In
      contrast, neither flood stress nor biotic stress significantly impacted viral
      internalization or dissemination. Additionally, the rates of TV internalization
      and dissemination in soil-grown lettuce were significantly higher than those for
      MNV-1. Collectively, these results demonstrated that (i) human NoV surrogates can
      be internalized via roots and disseminated to shoots and leaves of romaine
      lettuce grown in soil, (ii) abiotic stress (drought) but not biotic stress (LMV
      infection) affects the rates of viral internalization and dissemination, and
      (iii) the type of virus affects the efficiency of internalization and
      dissemination. This study also highlights the need to develop effective measures
      to eliminate internalized viruses in fresh produce. 

PMID- 25956774
TI  - Phytobeneficial Properties of Bacteria Isolated from the Rhizosphere of Maize in
      Southwestern Nigerian Soils.
AB  - Biocontrol agents isolated outside Africa have performed inconsistently under
      field conditions in Africa. The development of indigenous phytobeneficial
      microbial strains that suit local environments may help enhance competitiveness
      with in situ microorganisms and effectiveness at suppressing local pathogen
      strains. We isolated bacteria from the rhizosphere of maize growing in
      southwestern Nigeria and assessed them for growth-promoting characteristics. The
      best isolates were characterized using 16S rRNA genes and were further evaluated
      in the greenhouse on maize seedlings. Four isolates (EBS8, IGBR11, EPR2, and
      ADS14) were outstanding in in vitro assays of antagonistic activity against a
      local strain of Fusarium verticillioides, phosphate solubilization efficiency,
      chitinase enzyme activity, and indole-3-acetic acid production. Inoculation of
      maize seeds with these isolates resulted in >=95% maize seed germination and
      significantly enhanced radicle and plumule length. In the greenhouse, maize
      seedling height, stem girth, number of leaves, leaf area, shoot mass (dry
      matter), and nutrient contents were significantly enhanced. The bioprotectant and
      phytobeneficial effects were strongest and most consistent for isolate EBS8,
      which was identified as a Bacillus strain by 16S rRNA gene analysis. As a
      bacterial strain that exhibits multiple growth-promoting characteristics and is
      adapted to local conditions, EBS8 should be considered for the development of
      indigenous biological fertilizer treatments. 

PMID- 25956775
TI  - Thermal Inactivation Kinetics of Human Norovirus Surrogates and Hepatitis A Virus
      in Turkey Deli Meat.
AB  - Human noroviruses (HNoV) and hepatitis A virus (HAV) have been implicated in
      outbreaks linked to the consumption of presliced ready-to-eat deli meats. The
      objectives of this research were to determine the thermal inactivation kinetics
      of HNoV surrogates (murine norovirus 1 [MNV-1] and feline calicivirus strain F9
      [FCV-F9]) and HAV in turkey deli meat, compare first-order and Weibull models to
      describe the data, and calculate Arrhenius activation energy values for each
      model. The D (decimal reduction time) values in the temperature range of 50 to 72
      degrees C calculated from the first-order model were 0.1 +/- 0.0 to 9.9 +/- 3.9
      min for FCV-F9, 0.2 +/- 0.0 to 21.0 +/- 0.8 min for MNV-1, and 1.0 +/- 0.1 to
      42.0 +/- 5.6 min for HAV. Using the Weibull model, the tD = 1 (time to destroy 1
      log) values for FCV-F9, MNV-1, and HAV at the same temperatures ranged from 0.1
      +/- 0.0 to 11.9 +/- 5.1 min, from 0.3 +/- 0.1 to 17.8 +/- 1.8 min, and from 0.6
      +/- 0.3 to 25.9 +/- 3.7 min, respectively. The z (thermal resistance) values for
      FCV-F9, MNV-1, and HAV were 11.3 +/- 2.1 degrees C, 11.0 +/- 1.6 degrees C, and
      13.4 +/- 2.6 degrees C, respectively, using the Weibull model. The z values using
      the first-order model were 11.9 +/- 1.0 degrees C, 10.9 +/- 1.3 degrees C, and
      12.8 +/- 1.7 degrees C for FCV-F9, MNV-1, and HAV, respectively. For the Weibull
      model, estimated activation energies for FCV-F9, MNV-1, and HAV were 214 +/- 28,
      242 +/- 36, and 154 +/- 19 kJ/mole, respectively, while the calculated activation
      energies for the first-order model were 181 +/- 16, 196 +/- 5, and 167 +/- 9
      kJ/mole, respectively. Precise information on the thermal inactivation of HNoV
      surrogates and HAV in turkey deli meat was generated. This provided calculations
      of parameters for more-reliable thermal processes to inactivate viruses in
      contaminated presliced ready-to-eat deli meats and thus to reduce the risk of
      foodborne illness outbreaks. 

PMID- 25956777
TI  - Metabolism of Doubly para-Substituted Hydroxychlorobiphenyls by Bacterial
      Biphenyl Dioxygenases.
AB  - In this work, we examined the profile of metabolites produced from the doubly
      para-substituted biphenyl analogs 4,4'-dihydroxybiphenyl, 4-hydroxy-4'
      chlorobiphenyl, 3-hydroxy-4,4'-dichlorobiphenyl, and 3,3'-dihydroxy-4,4'
      chlorobiphenyl by biphenyl-induced Pandoraea pnomenusa B356 and by its biphenyl
      dioxygenase (BPDO). 4-Hydroxy-4'-chlorobiphenyl was hydroxylated principally
      through a 2,3-dioxygenation of the hydroxylated ring to generate 2,3-dihydro
      2,3,4-trihydroxy-4'-chlorobiphenyl and 3,4-dihydroxy-4'-chlorobiphenyl after the
      removal of water. The former was further oxidized by the biphenyl dioxygenase to
      produce ultimately 3,4,5-trihydroxy-4'-chlorobiphenyl, a dead-end metabolite. 3
      Hydroxy-4,4'-dichlorobiphenyl was oxygenated on both rings. Hydroxylation of the
      nonhydroxylated ring generated 2,3,3'-trihydroxy-4'-chlorobiphenyl with
      concomitant dechlorination, and 2,3,3'-trihydroxy-4'-chlorobiphenyl was
      ultimately metabolized to 2-hydroxy-4-chlorobenzoate, but hydroxylation of the
      hydroxylated ring generated dead-end metabolites. 3,3'-Dihydroxy-4,4'
      dichlorobiphenyl was principally metabolized through a 2,3-dioxygenation to
      generate 2,3-dihydro-2,3,3'-trihydroxy-4,4'-dichlorobiphenyl, which was
      ultimately converted to 3-hydroxy-4-chlorobenzoate. Similar metabolites were
      produced when the biphenyl dioxygenase of Burkholderia xenovorans LB400 was used
      to catalyze the reactions, except that for the three substrates used, the BPDO of
      LB400 was less efficient than that of B356, and unlike that of B356, it was
      unable to further oxidize the initial reaction products. Together the data show
      that BPDO oxidation of doubly para-substituted hydroxychlorobiphenyls may
      generate nonnegligible amounts of dead-end metabolites. Therefore, biphenyl
      dioxygenase could produce metabolites other than those expected, corresponding to
      dihydrodihydroxy metabolites from initial doubly para-substituted substrates.
      This finding shows that a clear picture of the fate of polychlorinated biphenyls
      in contaminated sites will require more insights into the bacterial metabolism of
      hydroxychlorobiphenyls and the chemistry of the dihydrodihydroxylated metabolites
      derived from them. 

PMID- 25956776
TI  - Giardia spp. Are Commonly Found in Mixed Assemblages in Surface Water, as
      Revealed by Molecular and Whole-Genome Characterization.
AB  - Giardia is the most common parasitic cause of gastrointestinal infections
      worldwide, with transmission through surface water playing an important role in
      various parts of the world. Giardia duodenalis (synonyms: G. intestinalis and G.
      lamblia), a multispecies complex, has two zoonotic subtypes, assemblages A and B.
      When British Columbia (BC), a western Canadian province, experienced several
      waterborne giardiasis outbreaks due to unfiltered surface drinking water in the
      late 1980s, collection of isolates from surface water, as well as from humans and
      beavers (Castor canadensis), throughout the province was carried out. To better
      understand Giardia in surface water, 71 isolates, including 29 from raw surface
      water samples, 29 from human giardiasis cases, and 13 from beavers in watersheds
      from this historical library were characterized by PCR. Study isolates also
      included isolates from waterborne giardiasis outbreaks. Both assemblages A and B
      were identified in surface water, human, and beavers samples, including a mixture
      of both assemblages A and B in waterborne outbreaks. PCR results were confirmed
      by whole-genome sequencing (WGS) for one waterborne outbreak and supported the
      clustering of human, water, and beaver isolates within both assemblages. We
      concluded that contamination of surface water by Giardia is complex, that the
      majority of our surface water isolates were assemblage B, and that both
      assemblages A and B may cause waterborne outbreaks. The higher-resolution data
      provided by WGS warrants further study to better understand the spread of
      Giardia. 

PMID- 25956778
TI  - Liposome-Encapsulated Bacteriophages for Enhanced Oral Phage Therapy against
      Salmonella spp.
AB  - Bacteriophages UAB_Phi20, UAB_Phi78, and UAB_Phi87 were encapsulated in
      liposomes, and their efficacy in reducing Salmonella in poultry was then studied.
      The encapsulated phages had a mean diameter of 309 to 326 nm and a positive
      charge between +31.6 and +35.1 mV (pH 6.1). In simulated gastric fluid (pH 2.8),
      the titer of nonencapsulated phages decreased by 5.7 to 7.8 log units, whereas
      encapsulated phages were significantly more stable, with losses of 3.7 to 5.4 log
      units. The liposome coating also improved the retention of bacteriophages in the
      chicken intestinal tract. When cocktails of the encapsulated and nonencapsulated
      phages were administered to broilers, after 72 h the encapsulated phages were
      detected in 38.1% of the animals, whereas the nonencapsulated phages were present
      in only 9.5%. The difference was significant. In addition, in an in vitro
      experiment, the cecal contents of broilers promoted the release of the phages
      from the liposomes. In broilers experimentally infected with Salmonella, the
      daily administration of the two cocktails for 6 days postinfection conferred
      similar levels of protection against Salmonella colonization. However, once
      treatment was stopped, protection by the nonencapsulated phages disappeared,
      whereas that provided by the encapsulated phages persisted for at least 1 week,
      showing the enhanced efficacy of the encapsulated phages in protecting poultry
      against Salmonella over time. The methodology described here allows the liposome
      encapsulation of phages of different morphologies. The preparations can be stored
      for at least 3 months at 4 degrees C and could be added to the drinking water and
      feed of animals. 

PMID- 25956779
TI  - Yersinia enterocolitica Isolates from Wild Boars Hunted in Lower Saxony, Germany.
AB  - Yersiniosis is strongly associated with the consumption of pork contaminated with
      enteropathogenic Yersinia enterocolitica, which is harbored by domestic pigs
      without showing clinical signs of disease. In contrast to data on Y.
      enterocolitica isolated from conventionally reared swine, investigations into the
      occurrence of Y. enterocolitica in wild boars in Germany are rare. The objectives
      of the study were to get knowledge about these bacteria and their occurrence in
      wild boars hunted in northern Germany by isolation of the bacteria from the
      tonsils, identification of the bioserotypes, determination of selected virulence
      factors, macrorestriction analysis, multilocus sequence typing (MLST), and
      testing of antimicrobial susceptibility. Altogether, tonsils from 17.1% of 111
      tested wild boars were positive for Y. enterocolitica by culture methods. All but
      two isolates belonged to biotype (BT) 1A, with the majority of isolates bearing a
      ystB nucleotide sequence which was revealed to have 85% identity to internal
      regions of Y. enterocolitica heat-stable enterotoxin type B genes. The remaining
      Y. enterocolitica isolates were identified to be BT 1B and did not carry the
      virulence plasmid. However, two BT 1A isolates carried the ail gene.
      Macrorestriction analysis and results from MLST showed a high degree of genetic
      diversity of the isolates, although the region where the samples were taken was
      restricted to Lower Saxony, Germany, and wild boars were shot during one hunting
      season. In conclusion, most Y. enterocolitica isolates from wild boars
      investigated in this study belonged to biotype 1A. Enteropathogenic Y.
      enterocolitica bioserotypes 4/O:3 and 2/O:9, usually harbored by commercially
      raised pigs in Europe, could not be identified. 

PMID- 25956780
TI  - Variation of radiocesium concentrations in cedar pollen in the Okutama area since
      the Fukushima Daiichi Nuclear Power Plant accident.
AB  - Due to releases of radionuclides in the Fukushima Daiichi Nuclear Power Plant
      accident, radiocesium ((134)Cs and (137)Cs) has been incorporated into large
      varieties of plant species and soil types. There is a possibility that
      radiocesium taken into plants is being diffused by pollen. Radiocesium
      concentrations in cedar pollen have been measured in Ome City, located in the
      Okutama area of metropolitan Tokyo, for the past 3 y. In this research, the
      variation of radiocesium concentrations was analysed by comparing data from 2011
      to 2014. Air dose rates at 1 m above the ground surface in Ome City from 2011 to
      2014 showed no significant difference. Concentration of (137)Cs contained in the
      cedar pollen in 2012 was about half that in 2011. Between 2012 and 2014, the
      concentration decreased by approximately one-fifth, which was similar to the
      result of a press release distributed by the Japanese Ministry of Agriculture,
      Forestry and Fisheries. 

PMID- 25956781
TI  - A high natural radiation area in Khao-Than hot spring, Southern Thailand.
AB  - Natural radioactivity in Khao-Than hot spring area, Surat Thani Province,
      Thailand was investigated. Gamma dose survey indicated a possible high radiation
      risk for this area. Rock, soil and hot spring mud samples were collected and
      analysed by a low background gamma spectrometer. The activity concentrations of
      (226)Ra, (232)Th and (40)K in samples were 151-139 092 (mean = 13 794), 12-596
      (127), 24-616 (215) Bq kg(-1), respectively. X-ray diffraction and Fourier
      transform infrared spectroscopy indicated that quartz and calcite (CaCO3) are the
      main constituents in mud samples with varying contents. In conclusion, this study
      area was reasonably classified as a high natural background radiation area. The
      source of radium in this area is supposed to be related to the fault fluids
      enriched in radium that precipitated with calcium in the carbonate terrain and
      partly absorbed by high cation exchange capacity clays. 

PMID- 25956782
TI  - Estimation of attached and unattached progeny of 222Rn and 220Rn concentration
      using deposition based progeny sensors.
AB  - The attached and unattached radon and thoron progeny concentrations have been
      calculated using deposition-based progeny sensors in Mansa, Muktsar, Bathinda and
      Faridkot districts of Punjab, India. The total (attached + unattached)
      equilibrium-equivalent (222)Rn concentration (EECRA + U) and total (attached +
      unattached) equilibrium-equivalent (220)Rn concentration (EECTA + U) were found
      to vary from 9 to 46 Bqm(-3) and 0.5 to 3.1 Bq m(-3), respectively. The
      concentrations of attached progeny nuclides for both (222)Rn and (220)Rn have
      been found to be greater than the unattached progeny nuclides in the dwellings of
      studied area. An attempt has also been made to assess the effective dose for
      (222)Rn and (220)Rn in the studied area. The radiation dose originated from
      (222)Rn and (220)Rn progeny is low and health risk is negligible. 

PMID- 25956783
TI  - Feasibility study for the assessment of the exposed dose with TENORM added in
      consumer products.
AB  - Consumer products including naturally occurring radioactive material have been
      distributed widely in human life. The potential hazard of the excessively added
      technically enhanced naturally occurring radioactive material (TENORM) in
      consumer products should be assessed. The aim of this study is to evaluate the
      organ equivalent dose and the annual effective dose with the usage of the TENORM
      added in paints. The activities of gammas emitted from natural radionuclides in
      the five types of paints were measured with the high-purity germanium detector,
      and the annual effective dose was assessed with the computational human phantom
      and the Monte Carlo method. The results show that uranium and thorium series were
      mainly measured over the five paints. Based on the exposure scenario of the
      paints in the room, the highest effective dose was evaluated as <1 mSv y(-1) of
      the public dose limit. 

PMID- 25956784
TI  - Natural radioactivity and effective dose due to the bottom sea and estuaries
      marine animals in the coastal waters around Peninsular Malaysia.
AB  - Malaysia is among the countries with the highest fish consumption in the world
      and relies on seafood as a main source of animal protein. Thus, the radioactivity
      in the mostly consumed marine animals such as fishes, crustaceans and molluscs
      collected from the coastal waters around Peninsular Malaysia has been determined
      to monitor the level of human exposure by natural radiation via seafood
      consumption. The mean activity concentrations of naturally occurring
      radionuclides (226)Ra ((238)U), (228)Ra ((232)Th) and (40)K ranged from 0.67 +/-
      0.19 Bq kg(-1) (Perna viridis) to 1.20 +/- 0.70 Bq kg(-1) (Rastrelliger), from
      0.19 +/- 0.17 Bq kg(-1) (Teuthida) to 0.82 +/- 0.67 Bq kg(-1) (Caridea) and from
      34 +/- 13 Bq kg(-1) (Caridea) to 48 +/- 24 Bq kg(-1) (Teuthida), respectively.
      The mean annual committed effective dose due to the individual radionuclides
      shows an order of (228)Ra > (226)Ra > (40)K in all marine samples. The obtained
      doses are less than the global internal dose of 290 uSv y(-1) set by the United
      Nations Scientific Committee on the Effects of Atomic Radiation, discarding any
      significant radiological risks to the populace of Peninsular Malaysia. 

PMID- 25956785
TI  - Measurement of the stochastic radial dose distribution for a 30-MeV proton beam
      using a wall-less tissue-equivalent proportional counter.
AB  - The frequency distribution of the lineal energy, y, of a 30-MeV proton beam was
      measured as a function of the radial distance from the beam path, and the dosed
      mean of y, y-(D), was obtained to investigate the radial dependence of y-(D). A
      wall-less tissue-equivalent proportional counter, in a cylindrical volume with
      simulated diameters of 0.36, 0.72 and 1.44 um was used for the measurement of y
      distributions, yf(y). The measured values of yf(y) summed in the radial direction
      agreed fairly well with the corresponding data taken from the microdosimetric
      calculations using the PHITS code. The y-(D) value of the 30-MeV proton beam
      presented its smallest value at r = 0.0 and gradually increased with radial
      distance, and the y-(D) values of heavy ions such as iron showed rapid decrease
      with radial distance. This experimental result demonstrated that the stochastic
      deposited energy distribution of high-energy protons in the microscopic region is
      rather constant in the core as well as in the penumbra region of the track
      structure.

PMID- 25956786
TI  - Measurement of 90Sr in contaminated Fukushima soils using liquid scintillation
      counter.
AB  - A method based on liquid scintillation counting system has been developed for the
      measurement of (90)Sr in Fukushima soil samples due to contamination of (134)Cs
      and (137)Cs. Three soil samples were collected within 30 km radius from the
      Fukushima Daiichi Nuclear Power Plant (FDNPP). Activity concentration of (134)Cs
      and (137)Cs were measured using a gamma spectroscopy system with high-purity
      germanium detector. (90)Sr contamination is little elevated but comparable with
      the background contamination level that originated from atmospheric nuclear
      weapon tests, whereas radiocesium contamination has increased significantly.
      Activity concentration of (90)Sr in the soil samples varied in the range of
      10.4+/-0.6-22.0+/-1.2 Bq kg(-1). Activity concentrations of (134)Cs and (137)Cs
      in the soil samples were in the range of 28.2+/-0.2-56.3+/-0.2 kBq kg(-1) and
      35.2+/-0.1-70.2+/-0.2 kBq kg(-1), respectively (reference date for decay
      correction is 1 December 2011). 

PMID- 25956787
TI  - Exposure assessment of microwave ovens and impact on total exposure in WLANs.
AB  - In situ exposure of electric fields of 11 microwave ovens is assessed in an
      occupational environment and in an office. Measurements as a function of distance
      without load and with a load of 275 ml of tap water were performed at distances
      of <1 m. The maximal measured field was 55.2 V m(-1) at 5 cm from the oven
      (without load), which is 2.5 and 1.1 times below the International Commission on
      Non-Ionizing Radiation Protection reference level for occupational exposure and
      general public exposure, respectively. For exposure at distances of >1 m, a model
      of the electric field in a realistic environment is proposed. In an office
      scenario, switching on a microwave oven increases the median field strength from
      91 to 145 mV m(-1) (+91 %) in a traditional Wireless Local Area Network (WLAN)
      deployment and from 44 to 92 mV m(-1) (+109 %) in an exposure-optimised WLAN
      deployment. 

PMID- 25956788
TI  - Pooled Bayesian meta-analysis of two Polish studies on radiation-induced cancers.
AB  - The robust Bayesian regression method was applied to perform meta-analysis of two
      independent studies on influence of low ionising radiation doses on the
      occurrence of fatal cancers. The re-analysed data come from occupational exposure
      analysis of nuclear workers in Swierk (Poland) and from ecological study of
      cancer risk from natural background radiation in Poland. Such two different types
      of data were analysed, and three popular models were tested: constant, linear and
      quadratic dose-response dependencies. The Bayesian model selection algorithm was
      used for all models. The Bayesian statistics clearly indicates that the popular
      linear no-threshold (LNT) assumption is not valid for presented cancer risks in
      the range of low doses of ionising radiation. The subject of LNT hypothesis use
      in radiation risk prediction and assessment is also discussed. 

PMID- 25956789
TI  - Letter to the Editor.

PMID- 25956790
TI  - In vitro platelet activation, aggregation and platelet-granulocyte complex
      formation induced by surface modified single-walled carbon nanotubes.
AB  - Surface modification of single-walled carbon nanotubes (SWCNTs) such as
      carboxylation, amidation, hydroxylation and pegylation is used to reduce the
      nanotube toxicity and render them more suitable for biomedical applications than
      their pristine counterparts. Toxicity can be manifested in platelet activation as
      it has been shown for SWCNTs. However, the effect of various surface
      modifications on the platelet activating potential of SWCNTs has not been tested
      yet. In vitro platelet activation (CD62P) as well as the platelet-granulocyte
      complex formation (CD15/CD41 double positivity) in human whole blood were
      measured by flow cytometry in the presence of 0.1mg/ml of pristine or various
      surface modified SWCNTs. The effect of various SWCNTs was tested by whole blood
      impedance aggregometry, too. All tested SWCNTs but the hydroxylated ones activate
      platelets and promote platelet-granulocyte complex formation in vitro.
      Carboxylated, pegylated and pristine SWCNTs induce whole blood aggregation as
      well. Although pegylation is preferred from biomedical point of view, among the
      samples tested by us pegylated SWCNTs induced far the most prominent activation
      and a well detectable aggregation of platelets in whole blood. 

PMID- 25956791
TI  - Dose-dependent lipid peroxidation induction on ex vivo intestine tracts exposed
      to chyme samples from fumonisins contaminated corn samples.
AB  - Fumonisins (FBs), Fusarium mycotoxins common food contaminant, are a potent
      inducer of oxidative stress and lipid peroxidation in intestinal cells. In order
      to verify this toxic effect in intestine tract, the aim was to assess lipid
      peroxidation (as malondialdehyde MDA increased levels) on intestine rat samples
      exposed to chyme samples from in vitro digestion of FBs contaminated corn
      samples. Naturally (9.61+/-3.2 MUg/gr), artificially (726+/-94 MUg/gr) and spiked
      corn samples at EU permitted FBs levels were digested and added to luminal side
      of Ussing chamber for 120 min. Fumonisins-free corn sample was used as control.
      The MDA increase was observed just in 83% of intestine samples exposed at EU FBs
      levels and the digestion process seems to reduce this incidence (50% of samples).
      Malondialdehyde levels were FBs dose- and subject-related and ranged from 0.07+/
      0.01 to 3.59+/-0.6 nmol/mg. Highest incidence and MDA % increment (I) were found
      when intestine tracts were exposed to chymes from artificially corn sample. The
      induction of lipid peroxidation induced by FBs could be due to interactions
      between FBs and intestinal membranes, with consequent modifications in membrane
      permeability and oxygen diffusion-concentration, as suggested by other authors.

PMID- 25956792
TI  - Breastfeeding Patterns in Preterm Infants Born at 28-33 Gestational Weeks.
AB  - BACKGROUND: Studies of breastfeeding patterns during preterm infants' first year
      of life are scarce but are important for providing breastfeeding mothers of
      preterm infants with optimal support. OBJECTIVE: This study aimed to describe
      breastfeeding patterns in preterm infants up to 1 year of corrected age. METHODS:
      As part of a larger study on kangaroo mother care in Sweden, a 24-hour
      breastfeeding diary was sent home after discharge from hospital, and at 2, 6, and
      12 months of the infant's corrected age. Eighty-three mothers responded to the
      follow-up questionnaires, and the number of respondents to the breastfeeding
      diary was 48 at discharge, 43 at 2 months, 22 at 6 months, and 8 at 12 months.
      Infants were born at a median (range) gestational age of 32 (28-33) weeks.
      Breastfeeding patterns were analyzed according to durations, frequencies per 24
      hours, and intervals between sessions. RESULTS: In exclusively breastfed infants,
      the median (range) breastfeeding session frequency was 14 (8-26) times per 24
      hours including 4 (1-9) times per night after discharge (n = 24) and 10 (6-25)
      times per 24 hours including 2 (0-5) times per night at 2 months (n = 23). In
      partially breastfed infants, the median (range) frequency was 5 (1-14) times per
      24 hours including 2 (0-4) times per night at 6 months (n = 20) and 5.5 (1-12)
      times per 24 hours including 2 (0-3) times per night at 12 months (n = 8).
      CONCLUSION: Mothers reported large variations in breastfeeding patterns, with
      higher median breastfeeding session frequencies than previously described in term
      infants in affluent settings.

PMID- 25956793
TI  - What does it take to evolve an enhancer? A simulation-based study of factors
      influencing the emergence of combinatorial regulation.
AB  - There is widespread interest today in understanding enhancers, which are
      regulatory elements typically harboring several transcription factor binding
      sites and mediating the combinatorial effect of transcription factors on gene
      expression. The evolution of enhancers poses interesting unanswered questions,
      for example, the evolutionary time taken for a typical enhancer to emerge or the
      factors shaping its evolution. Existing approaches to cis-regulatory evolution
      have often ignored the combinatorial nature and varied biochemical mechanisms of
      gene regulation encoded in enhancers. We report on our investigation of enhancer
      evolution through the use of PEBCRES, a framework for evolutionary simulation of
      enhancers that employs a mechanistic and well-supported sequence-to-expression
      model to assign fitness to the evolving enhancer genotype. We estimated the time
      necessary to evolve, from genomic background, enhancers capable of driving
      complex gene expression patterns similar to those involved in early development
      in Drosophila. We found the time-to-evolve to range between 0.5 and 10 Myr, and
      to vary greatly with the target expression pattern, complexity of the real
      enhancer known to encode that pattern, and the strength of input from specific
      transcription factors. To our knowledge, this is the first estimate of waiting
      times for realistic enhancers to evolve. The in silico evolved enhancers had,
      with a few interesting exceptions, site compositions similar to those seen in
      real enhancers for the same patterns. Our simulations also revealed that certain
      features of an enhancer might evolve not due to their biological function but as
      aids to the evolutionary process itself. 

PMID- 25956794
TI  - Transposable Elements and DNA Methylation Create in Embryonic Stem Cells Human
      Specific Regulatory Sequences Associated with Distal Enhancers and Noncoding
      RNAs.
AB  - Despite significant progress in the structural and functional characterization of
      the human genome, understanding of the mechanisms underlying the genetic basis of
      human phenotypic uniqueness remains limited. Here, I report that transposable
      element-derived sequences, most notably LTR7/HERV-H, LTR5_Hs, and L1HS, harbor
      99.8% of the candidate human-specific regulatory loci (HSRL) with putative
      transcription factor-binding sites in the genome of human embryonic stem cells
      (hESC). A total of 4,094 candidate HSRL display selective and site-specific
      binding of critical regulators (NANOG [Nanog homeobox], POU5F1 [POU class 5
      homeobox 1], CCCTC-binding factor [CTCF], Lamin B1), and are preferentially
      located within the matrix of transcriptionally active DNA segments that are
      hypermethylated in hESC. hESC-specific NANOG-binding sites are enriched near the
      protein-coding genes regulating brain size, pluripotency long noncoding RNAs,
      hESC enhancers, and 5-hydroxymethylcytosine-harboring regions immediately
      adjacent to binding sites. Sequences of only 4.3% of hESC-specific NANOG-binding
      sites are present in Neanderthals' genome, suggesting that a majority of these
      regulatory elements emerged in Modern Humans. Comparisons of estimated creation
      rates of novel TF-binding sites revealed that there was 49.7-fold acceleration of
      creation rates of NANOG-binding sites in genomes of Chimpanzees compared with the
      mouse genomes and further 5.7-fold acceleration in genomes of Modern Humans
      compared with the Chimpanzees genomes. Preliminary estimates suggest that
      emergence of one novel NANOG-binding site detectable in hESC required 466 years
      of evolution. Pathway analysis of coding genes that have hESC-specific NANOG
      binding sites within gene bodies or near gene boundaries revealed their
      association with physiological development and functions of nervous and
      cardiovascular systems, embryonic development, behavior, as well as development
      of a diverse spectrum of pathological conditions such as cancer, diseases of
      cardiovascular and reproductive systems, metabolic diseases, multiple
      neurological and psychological disorders. A proximity placement model is proposed
      explaining how a 33-47% excess of NANOG, CTCF, and POU5F1 proteins immobilized on
      a DNA scaffold may play a functional role at distal regulatory elements. 

PMID- 25956796
TI  - Pazopanib: a new drug for pancreatic neuroendocrine tumours.

PMID- 25956795
TI  - Pazopanib and depot octreotide in advanced, well-differentiated neuroendocrine
      tumours: a multicentre, single-group, phase 2 study.
AB  - BACKGROUND: Treatment options for advanced, well-differentiated neuroendocrine
      tumours (NETs) remain scarce. Pazopanib is an orally bioavailable, small
      molecule, multitargeted kinase inhibitor that inhibits VEGF receptors 1, 2, and
      3. We did a study of the efficacy of pazopanib with depot octreotide in patients
      with advanced NETs. METHODS: We did a parallel cohort study of patients with
      metastatic or locally advanced grade 1-2 carcinoid tumours or pancreatic NETs, by
      use of a single-group, two-stage design. Patients received pazopanib 800 mg
      orally once per day and octreotide at their preprotocol dosage. The primary
      endpoint was the proportion of patients achieving an objective response, as
      assessed by investigators, by intention-to-treat analysis. This study is
      registered with ClinicalTrials.gov, identifier NCT00454363, and was completed in
      March, 2014. FINDINGS: Between April 12, 2007, and July 2, 2009, we enrolled 52
      patients, including 32 individuals with pancreatic NETs and 20 individuals with
      carcinoid tumours. Seven (21.9%, 95% CI 11.0-38.8) of 32 patients with pancreatic
      NETs achieved an objective response. We detected no responses in the first stage
      of the cohort with carcinoid tumours, and we terminated accrual at 20 patients.
      Toxic effects included one patient with grade 4 hypertriglyceridaemia and one
      with grade 4 thrombosis, with the most common grade three events being
      aminotransferase increases and neutropenia, each of which happened in 3 patients.
      In all 52 patients, the most frequently observed toxic effects were fatigue (39
      [75%]), nausea (33 [63%]), diarrhoea (33 [63%]), and hypertension (28 [54%]).
      INTERPRETATION: Treatment with pazopanib is associated with tumour response for
      patients with pancreatic NETs, but not for carcinoid tumours; a randomised
      controlled phase 3 study to assess pazopanib in advanced pancreatic NETs is
      warranted. FUNDING: US National Cancer Institute of the National Institutes of
      Health.

PMID- 25956798
TI  - Aphid Sex Pheromone Compounds Interfere with Attraction of Common Green Lacewings
      to Floral Bait.
AB  - Common green lacewings (Chrysoperla carnea complex) form a group of generalist
      predators important for biological control. Several reports show attraction of
      these insects to plant volatiles, and a highly attractive ternary compound floral
      bait has been developed. With aphids being a preferred prey of larvae, one might
      expect these lacewings to be attracted to aphid semiochemicals, for instance, to
      aphid sex pheromones, as found for several other green lacewing species. However,
      in a previous study, we found that traps containing aphid sex pheromone compounds
      (1R,4aS,7S,7aR)-nepetalactol (NEPOH), (4aS,7S,7aR)-nepetalactone (NEPONE), and a
      ternary floral bait attracted fewer individuals than those containing the ternary
      floral bait alone. In the present study, possible causes for this effect of NEPOH
      and NEPONE on trap capture were studied. We established that C. carnea complex
      catches in traps with a ternary floral lure were not influenced by the presence
      of Chrysopa formosa individuals in traps (attracted by NEPOH and NEPONE) or by
      synthetic skatole (a characteristic component of Chrysopa defense secretion). A
      direct negative effect of NEPOH and NEPONE on attraction of C. carnea complex was
      found, suggesting active avoidance of these aphid sex pheromone components. This
      finding is surprising as the larvae of these lacewings prey preferentially on
      aphids. Possible mechanisms underlying this phenomenon are discussed. 

PMID- 25956797
TI  - An algorithm for assessment and treatment of postherniorrhaphy pain.
AB  - BACKGROUND: Inguinal pain after groin hernia repair is a challenging issue. About
      50 % of postherniorrhaphy pain allegedly is neuropathic, treatment of which is
      cumbersome given the limited efficacy of current therapeutic modalities. Possibly
      a clear protocol assessing the type of pain and treating it accordingly could
      improve its treatment. METHODS: A prospective study was done to evaluate an
      algorithm in patients with chronic postherniorrhaphy groin pain, aiming to select
      those with neuropathic pain and to treat appropriately. Treatment consisted of
      ultrasound-guided nerve blocks as an initial treatment for neuropathic pain. If
      long-term pain reduction proved inadequate, peripheral nerve stimulation was
      offered. RESULT: After our diagnostic workup consisting of anamnesis, physical
      examination and imaging, 68 patients out of 105 were diagnosed as having non
      neuropathic pain. These patients were referred to the most appropriate
      consultant, treated accordingly or sometimes pain appeared to be self-limiting.
      Thirty-seven (35 %) patients were diagnosed as having neuropathic pain with a
      median NRS of 7 (range 4-9) and were referred for further treatment to our pain
      clinic. The majority (21 of 28 patients) suffered ileo-inguinal nerve
      involvement. After ultrasound-guided nerve blocks, a permanent reduction in pain
      was achieved in 18 patients (62 %) with a median post-treatment NRS of 1 (range 0
      3). In six patients to which an additional peripheral nerve stimulator (PNS) was
      offered, pain reduction to a level of mild complaints with a median NRS of 2
      (range 1-8) was observed. In total, 24 of the 28 patients (83 %) diagnosed with
      neuropathic postherniorrhaphy pain achieved significant pain reduction after
      algorithm-based treatment. CONCLUSIONS: In the present study, we implemented a
      diagnostic workup for patients with postherniorrhaphy inguinal pain to select
      those with neuropathic pain. Eighty-three percent of the patients with
      neuropathic groin pain obtained significant improvement of their pain scores
      after our protocolled treatment. The effect was achieved by nerve infiltrations
      and in some cases by an implanted PNS when the former was unsuccessful.

PMID- 25956799
TI  - Choking under social pressure: social monitoring among the lonely.
AB  - Lonely individuals may decode social cues well but have difficulty putting such
      skills to use precisely when they need them--in social situations. In four
      studies, we examined whether lonely people choke under social pressure by asking
      participants to complete social sensitivity tasks framed as diagnostic of social
      skills or nonsocial skills. Across studies, lonely participants performed worse
      than nonlonely participants on social sensitivity tasks framed as tests of social
      aptitude, but they performed just as well or better than the nonlonely when the
      same tasks were framed as tests of academic aptitude. Mediational analyses in
      Study 3 and misattribution effects in Study 4 indicate that anxiety plays an
      important role in this choking effect. This research suggests that lonely
      individuals may not need to acquire social skills to escape loneliness; instead,
      they must learn to cope with performance anxiety in interpersonal interactions.

PMID- 25956800
TI  - Best of 2014.

PMID- 25956801
TI  - Acceleration of callus formation during fracture healing using basic fibroblast
      growth factor-kidney disease domain-collagen-binding domain fusion protein
      combined with allogenic demineralized bone powder.
AB  - BACKGROUND: To repair fractures with large bone defects or gaps, demineralized
      allogenic bone matrix (DBM) is often applied to the fracture site. However,
      studies have shown that the use of DBM alone has limited efficacy for repairing
      fractures. In the present study, we developed an allogenic demineralized bone
      powder (DBP) with basic fibroblast-derived growth factor containing a polycystic
      kidney disease (PKD) domain and collagen-binding domain (CBD) from Clostridium
      histolyticum collagenase (ColH) and investigated the stimulatory effects of bFGF
      PKD-CBD combined with allogenic DBP on bone growth in a mouse femur fracture
      model. METHODS: DBP mixed with either phosphate-buffered saline (PBS) (DBP/PBS),
      0.58 nmol basic fibroblast growth factor (bFGF) (0.58 nmol DBP/bFGF), 0.058 nmol
      bFGF-PKD-CBD (0.058 nmol DBP/bFGF-PKD-CBD), or 0.58 nmol bFGF-PKD-CBD (0.58 nmol
      DBP/bFGF-PKD-CBD) was grafted into fracture sites. RESULTS: bFGF-PKD-CBD/DBP
      composite accelerates callus formation in a bone fracture model in mice and
      clearly showed that the composite also increases bone mineral density at fracture
      sites compared to bFGF/DBP. In addition, bFGF-PKD-CBD/DBP increased callus volume
      and bone mineral content to similar levels in fractures treated with a tenfold
      higher amount of bFGF at 4 weeks. CONCLUSIONS: Our results suggest that bFGF-PKD
      CBD/DBP may be useful for promoting fracture healing in the clinical setting.

PMID- 25956802
TI  - Ethnic disparity in defensive coping endothelial responses: The SABPA study.
AB  - OBJECTIVES: Defensive coping (DefS) in Blacks has been associated with greater
      cardiovascular risk than in their White counterparts. We examined associations
      between endothelial function mental stress responses and markers of vascular
      structure in a bi-ethnic cohort. METHODS: We examined vascular function and
      structure in 368 Black (43.84+/-8.31years) and White Africans (44.78+/
      10.90years). Fasting blood samples, 24h blood pressure, left carotid intima-media
      thickness of the far wall (L-CIMTf), and left carotid cross-sectional wall area
      (L-CSWA) values were obtained. von Willebrand factor (VWF), endothelin-1 (ET-1)
      and nitric oxide metabolite (NOx) responses to the Stroop mental stress test were
      calculated to assess endothelial function. DefS was assessed using the Coping
      Strategy Indicator questionnaire. Interaction between main effects was
      demonstrated for 283 participants with DefS scores above the mean of 26 for L
      CIMTf. RESULTS: Blunted stress responses for VWF (men 16.71% vs. 51.10%; women
      0.85% vs. 42.09%, respectively) and NOx (men -64.52% vs. 74.89%; women -76.16%
      vs. 113.29%, respectively) were evident in the DefS Blacks compared to the DefS
      Whites (p<0.001). ET-1 increased more in Blacks (men 150% and women 227%,
      p<0.001) compared to the Whites (men 61.25% and women 35.49%, p<0.001).
      Ambulatory pulse pressure, but not endothelial function markers, contributed to L
      CIMTf (DeltaR(2)=0.11 p<0.001), and L-CSWA (DeltaR(2)=0.08, p<0.001) in DefS
      African men but not in any other group. CONCLUSIONS: Blunted stress-induced NOx
      and VWF responses and augmented ET-1 responses in DefS Blacks indicate
      endothelial dysfunction. DefS may facilitate disturbed endothelial responses and
      enforce vascular remodelling via compensatory increases in pulse pressure in
      Black men. These observations may indicate an increased risk of cardiovascular
      incidents via functional and structural changes of the vasculature in DefS
      Blacks.

PMID- 25956803
TI  - Stable isotope labelling methods in mass spectrometry-based quantitative
      proteomics.
AB  - Mass-spectrometry based proteomics has evolved as a promising technology over the
      last decade and is undergoing a dramatic development in a number of different
      areas, such as; mass spectrometric instrumentation, peptide identification
      algorithms and bioinformatic computational data analysis. The improved
      methodology allows quantitative measurement of relative or absolute protein
      amounts, which is essential for gaining insights into their functions and
      dynamics in biological systems. Several different strategies involving stable
      isotopes label (ICAT, ICPL, IDBEST, iTRAQ, TMT, IPTL, SILAC), label-free
      statistical assessment approaches (MRM, SWATH) and absolute quantification
      methods (AQUA) are possible, each having specific strengths and weaknesses.
      Inductively coupled plasma mass spectrometry (ICP-MS), which is still widely
      recognised as elemental detector, has recently emerged as a complementary
      technique to the previous methods. The new application area for ICP-MS is
      targeting the fast growing field of proteomics related research, allowing
      absolute protein quantification using suitable elemental based tags. This
      document describes the different stable isotope labelling methods which
      incorporate metabolic labelling in live cells, ICP-MS based detection and post
      harvest chemical label tagging for protein quantification, in addition to
      summarising their pros and cons. 

PMID- 25956804
TI  - Long-term trends in tourism climate index scores for 40 stations across Iran: the
      role of climate change and influence on tourism sustainability.
AB  - Tourism is a rapidly growing international sector and relies intrinsically on an
      amenable climate to attract visitors. Climate change is likely to influence the
      locations preferred by tourists and the time of year of peak travel. This study
      investigates the effect of climate change on the Tourism Climate Index (TCI) for
      Iran. The paper first calculates the monthly TCI for 40 cities across Iran for
      each year from 1961 to 2010. Changes in the TCI over the study period for each of
      the cities are then explored. Increases in TCI are observed for at least one
      station in each month, whilst for some months no decreases occurred. For October,
      the maximum of 45% of stations demonstrated significant changes in TCI, whilst
      for December only 10% of stations demonstrated change. The stations Kashan,
      Orumiyeh, Shahrekord, Tabriz, Torbat-e-Heidarieh and Zahedan experienced
      significant increases in TCI for over 6 months. The beginning of the change in
      TCI is calculated to have occurred from 1970 to 1980 for all stations. Given the
      economic dependence on oil exports, the development of sustainable tourism in
      Iran is of importance. This critically requires the identification of locations
      most suitable for tourism, now and in the future, to guide strategic investment.

PMID- 25956805
TI  - Increased mortality associated with extreme-heat exposure in King County,
      Washington, 1980-2010.
AB  - Extreme heat has been associated with increased mortality, particularly in
      temperate climates. Few epidemiologic studies have considered the Pacific
      Northwest region in their analyses. This study quantified the historical (May to
      September, 1980-2010) heat-mortality relationship in the most populous Pacific
      Northwest County, King County, Washington. A relative risk (RR) analysis was used
      to explore the relationship between heat and all-cause mortality on 99th
      percentile heat days, while a time series analysis, using a piece-wise linear
      model fit, was used to estimate the effect of heat intensity on mortality,
      adjusted for temporal trends. For all ages, all causes, we found a 10% (1.10 (95%
      confidence interval (CI), 1.06, 1.14)) increase in the risk of death on a heat
      day versus non-heat day. When considering the intensity effect of heat on all
      cause mortality, we found a 1.69% (95% CI, 0.69, 2.70) increase in the risk of
      death per unit of humidex above 36.0 degrees C. Mortality stratified by cause and
      age produced statistically significant results using both types of analyses for:
      all-cause, non-traumatic, circulatory, cardiovascular, cerebrovascular, and
      diabetes causes of death. All-cause mortality was statistically significantly
      modified by the type of synoptic weather type. These results demonstrate that
      heat, expressed as humidex, is associated with increased mortality on heat days,
      and that risk increases with heat's intensity. While age was the only individual
      level characteristic found to modify mortality risks, statistically significant
      increases in diabetes-related mortality for the 45-64 age group suggests that
      underlying health status may contribute to these risks.

PMID- 25956807
TI  - Erratum to: Effects of heat stress on the gene expression of nutrient
      transporters in the jejunum of broiler chickens (Gallus gallus domesticus).

PMID- 25956806
TI  - Biological effects of the electrostatic field: red blood cell-related alterations
      of oxidative processes in blood.
AB  - The aim of this study was to determine activities of pro-/antioxidant enzymes,
      reactive oxygen species (ROS) content, and oxidative modification of proteins and
      lipids in red blood cells (RBCs) and blood plasma of rats exposed to
      electrostatic field (200 kV/m) during the short (1 h) and the long periods (6
      day, 6 h daily). Short-term exposure was characterized by the increase of
      oxidatively damaged proteins in blood of rats. This was strongly expressed in RBC
      membranes. After long-term action, RBC content in peripheral blood was higher
      than in control (P < 0.01) and the attenuation of prooxidant processes was shown.
      HIGHLIGHTS: External electrostatic field (200 kV/m) alters the balance in pro
      /antioxidant processes. We examine oxidative processes in plasma and RBC
      (hemolysate and membranes). Biological effects of static electric field depend on
      exposure time. Acute action of electrostatic field (ESF) characterized by
      activation of the prooxidant processes. Long-term exposure reflected with
      prevalence of antioxidant activities.

PMID- 25956808
TI  - Endophytic bacteria from wheat grain as biocontrol agents of Fusarium graminearum
      and deoxynivalenol production in wheat.
AB  - In Uruguay, Fusarium graminearum is the most common species that infects wheat
      and is responsible for Fusarium head blight (FHB) and contamination of grain with
      deoxynivalenol (DON). The aim of this work was to select bacterial endophytes
      isolated from wheat grain to evaluate their antagonistic ability against F.
      graminearum and DON production in vitro and under field conditions. Four strains
      identified as Bacillus megaterium (BM1) and Bacillus subtilis (BS43, BSM0 y BSM2)
      significantly reduced fungal growth and spore germination of F. graminearum. This
      antagonist activity remained unchanged after the bacterial cultures were heat
      treated. Under field conditions, treatments with antagonist BM1 was the most
      effective, reducing the FHB incidence and severity by 93 and 54 %, respectively,
      and the production of DON by 89.3 %.

PMID- 25956811
TI  - [Histological workup of enucleated eyes].
AB  - The appraisal of enucleated eyes presents a particular challenge to pathologists.
      In German-speaking countries, this task has mostly been in the hands of
      ophthalmologists. It requires particular ophthalmologic knowledge including
      nosology, implants, surgical procedures, and nomenclature. This CME article
      teaches the basics needed for pathologic appraisal of enucleated eyes. The first
      part focusses on the macroscopic evaluation and describes the exterior and
      interior of the eye. Competent interpretation of the macroscopic findings is
      crucial to identify adequate cutting planes for histology. Anatomic landmarks on
      the globe's exterior and common section planes are described. Diseases that
      typically lead to enucleation will be explained in detail and illustrated with
      images. In the second part of this article, a histologic description of eye
      specific tissue types is provided. 

PMID- 25956809
TI  - Axon diameter and axonal transport: In vivo and in vitro effects of androgens.
AB  - Testosterone is a sex hormone involved in brain maturation via multiple molecular
      mechanisms. Previous human studies described age-related changes in the overall
      volume and structural properties of white matter during male puberty. Based on
      this work, we have proposed that testosterone may induce a radial growth of the
      axon and, possibly, modulate axonal transport. In order to determine whether this
      is the case we have used two different experimental approaches. With electron
      microscopy, we have evaluated sex differences in the structural properties of
      axons in the corpus callosum (splenium) of young rats, and tested consequences of
      castration carried out after weaning. Then we examined in vitro the effect of the
      non-aromatizable androgen Mibolerone on the structure and bidirectional transport
      of wheat-germ agglutinin vesicles in the axons of cultured sympathetic neurons.
      With electron microscopy, we found robust sex differences in axonal diameter
      (males>females) and g ratio (males>females). Removal of endogenous testosterone
      by castration was associated with lower axon diameter and lower g ratio in
      castrated (vs. intact) males. In vitro, Mibolerone influenced the axonal
      transport in a time- and dose-dependent manner, and increased the axon caliber as
      compared with vehicle-treated neurons. These findings are consistent with the
      role of testosterone in shaping the axon by regulating its radial growth, as
      predicted by the initial human studies. 

PMID- 25956813
TI  - [Pulmonary neuroendocrine tumors in the new WHO 2015 classification: Start of
      breaking new grounds?].
AB  - CLASSIFICATION: In the recently published 4th edition of the World Health
      Organization (WHO) classification of tumors of the lungs, pleura, thymus and
      heart, all neuroendocrine tumors of the lungs (pNET) are presented for the first
      time in one single chapter following adenocarcinoma and squamous cell carcinoma
      and before large cell carcinoma. In this classification, high grade small cell
      lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) are
      differentiated from intermediate grade atypical carcinoids (AC) and low grade
      typical carcinoids as well as from preinvasive lesions (DIPNECH). In the 3rd WHO
      classification from 2004, which dealt with resection specimens, SCLC and
      carcinoids each had a separate chapter and LCNEC was previously listed in the
      chapter on large cell carcinoma of the lungs. The new WHO classification is for
      the first time also applicable to lung biopsies. DIAGNOSTICS: Normally, common
      features of all pNET are a neuroendocrine morphology (as far as detectable in
      small biopsies) and expression of the neuroendocrine (NE) markers (chromogranin
      A, synaptophysin and CD56/NCAM). An immunohistochemical positive staining of at
      least one NE marker was already recommended in the 3rd edition of the WHO
      classification (2004) only for LCNEC. Differentiating features are a small or
      large cell cytomorphology/histomorphology, nuclear criteria and the mitotic rate
      (for SCLC >10 with a median of 80, for LCNEC >10 median 70, for AC 2 - 10, for TC
      < 2 each per 2 mm(2)). Tumor cell necrosis usually occurs in SCLC and LCNEC,
      partially in AC and not in TC. The guideline Ki67 proliferation rates are given
      for the first time in the new WHO classification for SCLC as 50-100 %, for LCNEC
      40-80 %, for AC up to 20 % and for TC up to 5 %. MOLECULAR PATHOLOGY: Molecular
      alterations occur in SCLC and LCNEC in large numbers and are very variable in
      quality. In AC and TC they occur much less frequently and are relatively similar.
      CONCLUSION: The direct comparison of all pNET in one chapter facilitates the
      differential diagnostics of these tumors, provides a better transparency
      especially of LCNEC and allows a further comprehensive development of the
      clinical practical and scientific evaluation of pNET. Although a separate
      terminology of pNET is maintained for the lungs, a careful approach towards the
      gastroentero-pancreatic NET (gepNET) can be observed.

PMID- 25956814
TI  - Access site complications following transfemoral coronary procedures: comparison
      between traditional compression and angioseal vascular closure devices for
      haemostasis.
AB  - BACKGROUND: Vascular closure devices such as angioseal are used as alternatives
      to traditional compression haemostasis. Although the safety and efficacy of
      angioseal are confirmed, their use remains controversial because of the potential
      complications of these devices compared with those of traditional compression
      haemostasis. The aim of this study was to compare the access site complication
      rate, the predictive factors for these complications, and patient comfort levels
      after coronary procedures with traditional compression or angioseal haemostasis.
      METHODS: Data were collected from a cardiac unit in a medical center in northern
      Taiwan. A total of 130 adult patients were recruited and equally divided into two
      groups according to the method of haemostasis used after the coronary procedure:
      a traditional compression group and an angioseal group. We observed the incidence
      of access site complications, including bleeding, oozing, haematoma formation,
      and arteriovenous fistula formation. In addition, we used a 0-10 numeric rating
      scale to assess soreness, numbness, and back and groin access site pain after 1 h
      of catheter removal and immediately before getting out of bed. RESULTS: The
      overall incidence of complications was 3.8 % (n = 5), which was not significantly
      different between the two groups (p = .06). The propensity score--adjusted
      multivariate analyses revealed that the only independent predictor for access
      site complications was an age of >70 years (OR, 10.44; 95 % CI, 1.81-60.06; p =
      .009). Comfort levels were higher in the angioseal group than in the traditional
      compression group. CONCLUSIONS: Angioseal used after coronary procedures did not
      increase the incidence of complications relative to that associated with
      traditional compression haemostasis; however, it increased patient comfort
      levels. Health personnel should pay special attention to the predictive factor
      for access site complications after coronary procedures, such as age >70 years.

PMID- 25956816
TI  - Effects of kelp phenolic compounds on the feeding-associated mobility of the
      herbivore snail Tegula tridentata.
AB  - Tegula tridentata, is a common herbivore gastropod inhabiting the subtidal
      Lessonia trabeculata kelp forest, which tends to show higher densities after kelp
      harvesting. We investigated if harvested kelp beds may harbor higher densities of
      herbivore invertebrates, and the underlying mechanisms. Thus, we evaluated if the
      exudates of L. trabeculata change the seawater levels of soluble phenols, known
      to have a deterrent effect against the feeding behavior of some herbivore
      invertebrates. Finally we investigated whether the increase in T. tridentata
      densities in harvested kelp grounds could be related to a decrease in the
      seawater levels of soluble phenols. Our results showed that the density of
      invertebrate herbivores increased up to 32% in harvested kelp grounds. We provide
      the first estimate of the rate of phenolic exudation by L. trabeculata, and we
      demonstrate that T. tridentata changes its food dependent movement in the
      presence of exudates with synthetic phloroglucinol. We suggest that the recovery
      of harvested kelp ecosystems can be jeopardized by increased herbivory triggered
      by water-borne changes in the levels of herbivore deterrent compounds. 

PMID- 25956815
TI  - Non-dopamine receptor ligands for the treatment of Parkinson's disease. Insight
      into the related chemical/property space.
AB  - Extensive biochemical and clinical studies have increasingly recognized
      Parkinson's disease as a highly complex and multi-faceted neurological disorder
      having branched non-motor symptoms including sleep disorders, pain, constipation,
      psychosis, depression, and fatigue. A wide range of biological targets in the
      brain deeply implicated in this pathology resulted in a plethora of novel small
      molecule compounds with promising activity. This review thoroughly describes the
      chemical space of non-dopamine receptor ligands in terms of diversity,
      isosteric/bioisosteric morphing, and molecular descriptors. 

PMID- 25956817
TI  - Response to the Article on Dimethyl Sulfoxide-Cryopreserved Platelets Published
      in Transfusion Medicine Reviews Volume 28(4).

PMID- 25956818
TI  - Oviposition in the blood-sucking insect Rhodnius prolixus is modulated by host
      odors.
AB  - BACKGROUND: Triatomine bugs are blood-sucking insects, vectors of Chagas disease.
      Despite their importance, their oviposition behavior has received relatively
      little attention. Some triatomines including Rhodnius prolixus stick their eggs
      to a substrate. It is known that mechanical cues stimulate oviposition in this
      species. However, it is not clear if chemical signals play a role in this
      behavior. We studied the role of host cues, including host odor, in the
      oviposition behavior of the triatomine R. prolixus. METHODS: Tests were carried
      out in an experimental arena and stimuli consisted of a mouse or hen feathers.
      The number of eggs laid and the position of those eggs with respect to the
      stimulus source were recorded. Data were analyzed using the Mann-Whitney and
      Kruskal-Wallis tests. RESULTS: Both a mouse and hen feathers stimulated
      oviposition. In addition, hen feathers evoked a particular spatial distribution
      of eggs that was not observed in the case of mouse. CONCLUSIONS: We propose that
      volatile chemical cues from the host play a role in the oviposition behavior of
      triatomines that stick their eggs. Thus, host odor would stimulate and spatially
      guide oviposition.

PMID- 25956820
TI  - The influence of the channel size on the reduction of side effects in
      microchannel proton therapy.
AB  - The potential of proton microchannel radiotherapy to reduce radiation effects in
      the healthy tissue but to keep tumor control the same as in conventional proton
      therapy is further elucidated. The microchannels spread on their way to the tumor
      tissue resulting in different fractions of the healthy tissue covered with doses
      larger than the tumor dose, while the tumor gets homogeneously irradiated. The
      aim of this study was to evaluate the effect of increasing channel width on
      potential side effects in the normal tissue. A rectangular 180 * 180 um(2) and
      two Gaussian-type dose distributions of sigma = 260 um and sigma = 520 um with an
      interchannel distance of 1.8 mm have been applied by 20-MeV protons to a 3D human
      skin model in order to simulate the widened channels and to compare the
      irradiation effects at different endpoints to those of a homogeneous proton
      irradiation. The number of protons applied was kept constant at all irradiation
      modes resulting in the same average dose of 2 Gy. All kinds of proton
      microchannel irradiation lead to higher cell viability and produce significantly
      less genetic damage than homogeneous proton irradiation, but the reduction is
      lower for the wider channel sizes. Our findings point toward the application of
      microchannel irradiation for clinical proton or heavy ion therapy to further
      reduce damage of normal tissues while maintaining tumor control via a homogeneous
      dose distribution inside the tumor.

PMID- 25956819
TI  - Vapoenucleation of the prostate using a high-power thulium laser: a one-year
      follow-up study.
AB  - BACKGROUND: Prostate vaporization and enucleation is a novel treatment option for
      bladder outlet obstruction caused by benign prostate enlargement. This surgical
      technique, however, has not yet been standardized. We present our findings of
      using a high-power thulium laser to accomplish vapoenucleation of the prostate
      (ThuVEP). METHODS: We prospectively collected and analyzed data from 29 patients
      who underwent ThuVEP between August 2010 and May 2012. The control group included
      30 patients who underwent traditional transurethral resection of the prostate
      (TURP). Operative variables, patient profiles, preoperative and postoperative
      urine flow rates, prostate volume (measured using transrectal ultrasonography),
      and the international prostate symptom score (IPSS) were recorded and analyzed
      using a two-tailed Student's t-test and analysis of variance. RESULTS: The ages
      (mean +/- SD) of the patients were 76.1 +/- 9.4 and 72.6 +/- 7.4 years (p = 0.28)
      in the ThuVEP and TURP groups, respectively. The average urinary flow rates
      before and 12 months after the operation (volume/maximum flow/average flow) were
      243.3/10.5/5.0 and 302.8/17.6/9.4 (in mL, mL/s, mL/s, respectively) in the ThuVEP
      group and 247.2/10.8/4.6 and 369.9/20.8/12.0, respectively, in the TURP group.
      Preoperative and postoperative IPSSs were 17.1 +/- 5.0 and 6.5 +/- 3.8,
      respectively, in the ThuVEP group and 18.2 +/- 4.5 and 6.2 +/- 3.3, respectively,
      in the TURP group. The mean ratio of the estimated postoperative residual
      prostate volume to the preoperative total volume was 0.47 (p = 0.449) in both
      groups. The overall complication rate was 20.7% in the ThuVEP group and 30.0% in
      the TURP group. CONCLUSIONS: One year of follow-up showed that ThuVEP and TURP
      effectively alleviated subjective and objective voiding symptoms with a low rate
      of complications. Thus, vapoenucleation using a high-power laser is feasible in
      elderly patients. TRIAL REGISTRATION: ISRCTN registry with study ID
      ISRCTN52339705 . Date assigned: 06/03/2015.

PMID- 25956821
TI  - Modeling radiation-induced cell death: role of different levels of DNA damage
      clustering.
AB  - Some open questions on the mechanisms underlying radiation-induced cell death
      were addressed by a biophysical model, focusing on DNA damage clustering and its
      consequences. DNA "cluster lesions" (CLs) were assumed to produce independent
      chromosome fragments that, if created within a micrometer-scale threshold
      distance (d), can lead to chromosome aberrations following mis-rejoining; in
      turn, certain aberrations (dicentrics, rings and large deletions) were assumed to
      lead to clonogenic cell death. The CL yield and d were the only adjustable
      parameters. The model, implemented as a Monte Carlo code called BIophysical
      ANalysis of Cell death and chromosome Aberrations (BIANCA), provided simulated
      survival curves that were directly compared with experimental data on human and
      hamster cells exposed to photons, protons, alpha-particles and heavier ions
      including carbon and iron. d = 5 MUm, independent of radiation quality, and CL
      yields in the range ~2-20 CLs Gy(-1) cell(-1), depending on particle type and
      energy, led to good agreement between simulations and data. This supports the
      hypothesis of a pivotal role of DNA cluster damage at sub-micrometric scale,
      modulated by chromosome fragment mis-rejoining at micrometric scale. To
      investigate the features of such critical damage, the CL yields were compared
      with experimental or theoretical yields of DNA fragments of different sizes,
      focusing on the base-pair scale (related to the so-called local clustering), the
      kbp scale ("regional clustering") and the Mbp scale, corresponding to chromatin
      loops. Interestingly, the CL yields showed better agreement with kbp fragments
      rather than bp fragments or Mbp fragments; this suggests that also regional
      clustering, in addition to other clustering levels, may play an important role,
      possibly due to its relationship with nucleosome organization in the chromatin
      fiber. 

PMID- 25956823
TI  - A misunderstood comment, on a misattributed error in a study manuscript: pulsed
      radiofrequency treatment as compared to conventional radiofrequency neurotomy for
      facet joint pain.

PMID- 25956822
TI  - Does nutrient sensing determine how we "see" food?
AB  - The ability to "see" both incoming and circulating nutrients plays an essential
      role in the maintenance of energy homeostasis. As such, nutrient-sensing
      mechanisms in both the gastrointestinal tract and the brain have been implicated
      in the regulation of energy intake and glucose homeostasis. The intestinal wall
      is able to differentiate individual nutrients through sensory machinery expressed
      in the mucosa and provide feedback signals, via local gut peptide action, to
      maintain energy balance. Furthermore, both the hypothalamus and hindbrain detect
      circulating nutrients and respond by controlling energy intake and glucose
      levels. Conversely, nutrient sensing in the intestine plays a role in stimulating
      food intake and preferences. In this review, we highlight the emerging evidence
      for the regulation of energy balance through nutrient-sensing mechanisms in the
      intestine and the brain, and how disruption of these pathways could result in the
      development of obesity and type 2 diabetes.

PMID- 25956824
TI  - [Stem cell transplantation for multiple sclerosis. Hamburg experiences and state
      of international research].
AB  - BACKGROUND: Autologous hematopoietic stem cell transplantation (aHSCT) is still
      not the standard treatment for highly inflammatory multiple sclerosis (MS). Even
      though randomized controlled trials are lacking, predictors for treatment
      response have been established. Since 2007, ten patients have received aHSCT in
      Hamburg. OBJECTIVE: To present observational data from patients treated in
      Hamburg and a review of the literature. METHODS: Descriptive statistics were used
      for evaluating the course of the expanded disability status scale (EDSS) as a
      measure for clinical outcome, magnetic resonance imaging (MRI) and
      neuropsychology. New gadolinium and T2-MRI uptake lesions per scan were compared.
      In addition, a systematic review of the currently available literature was
      performed. RESULTS: The Hamburg series can be divided in two groups, one group
      including four patients with chronic progressive MS with low inflammatory
      activity (median EDSS = 6.25, 0.5 relapses per year, no gadolinium-enhancing
      lesions) and the other group including six patients with mild to moderate
      disability, relapses and inflammatory activity (median EDSS = 4.25, 1 relapse per
      year, 2 gadolinium-enhancing lesions). The median follow-up was 2.4 years. While
      the first group did not seem to benefit from aHSCT, an improvement in five out of
      six patients was observed in the second group. New T2 lesions occurred within the
      first 6 months but gadolinium-enhancing lesions were not observed (p < 0.05). A
      systematic literature search identified a higher efficacy of aHSCT in younger,
      less disabled MS patients with inflammatory activity, similar to the findings
      from Hamburg. CONCLUSION: Cohort reports describe aHSCT as a safe and efficient
      treatment option in highly inflammatory MS. Based on these data aHSCT seems to be
      a reasonable option in selected patients with highly inflammatory MS but a
      randomized controlled trial is warranted.

PMID- 25956825
TI  - Assessing the Quality of Osteoporosis Care in Practice.
AB  - BACKGROUND: Patients with osteoporosis can sustain fractures following falls or
      other minimal trauma. This risk of fracture can be reduced through appropriate
      diagnostic testing, pharmacologic therapy, and other readily measured standards
      of care. OBJECTIVES: Our aim was to develop a credible clinical performance
      assessment to measure physicians' quality of osteoporosis care, and determine
      reasonable performance standards for both competent and excellent care. DESIGN:
      This was a retrospective cohort study. PARTICIPANTS: Three hundred and eighty one
      general internists and subspecialists with time-limited board certification were
      included in the study. MAIN MEASURES: Performance rates on eight evidence-based
      measures were obtained from the American Board of Internal Medicine (ABIM)
      Osteoporosis Practice Improvement Module(r) (PIM), a web-based tool that uses
      medical chart reviews to help physicians assess and improve care. We applied a
      patented methodology, using an adaptation of the Angoff standard-setting method
      and the Dunn-Rankin method, with an expert panel skilled in osteoporosis care to
      form a composite and establish standards for both competent and excellent care.
      Physician and practice characteristics, including a practice infrastructure score
      based on the Physician Practice Connections Readiness Survey (PPC-RS), were used
      to examine the validity of the inferences made from the composite scores. KEY
      RESULTS: The mean composite score was 67.54 out of 100 maximum points with a
      reliability of 0.92. The standard for competent care was 46.87, and for excellent
      care it was 83.58. Both standards had high classification accuracies (0.95).
      Sixteen percent of physicians performed below the competent care standard, while
      22 % met the excellent care standard. Specialists scored higher than generalists,
      and better practice infrastructure was associated with higher composite scores,
      providing some validity evidence. CONCLUSIONS: We developed a rigorous
      methodology for assessing physicians' osteoporosis care. Clinical performance
      feedback relative to absolute standards of care provides physicians with a
      meaningful approach to self-evaluation to improve patient care.

PMID- 25956827
TI  - Antioxidant and acetylcholinesterase inhibition properties of novel bromophenol
      derivatives.
AB  - In this study, series of novel bromophenol derivatives were synthesized and
      investigated for their antioxidant and AChE inhibition properties. Novel
      brominated diarylmethanones were obtained from the acylation reactions of benzoic
      acids with substituted benzenes. One of the bromodiarylmethanone was synthesized
      from the bromination of diarylmethanone with molecular bromine. All
      diarylmethanones were converted into their bromophenol derivatives with BBr3. The
      antioxidant activities of all synthesized compounds were elucidated by using
      various bioanalytical assays. Radical scavenging activities of compounds 10-24
      were evaluated by means of DPPH and ABTS(+) scavenging activities. In addition,
      reducing ability of 10-24 were determined by Fe(3+), Cu(2+), and [Fe(3+)
      (TPTZ)2](3) reducing activities. alpha-Tocopherol, trolox, BHA, and BHT were used
      as positive antioxidant and radical scavenger molecules. On the other hand, IC50
      values were calculated for DPPH, ABTS(+) scavenging, and AChE inhibition effects
      of novel compounds. The results obtained from the current studies clearly show
      that novel bromophenol derivatives 20-24 have considerable antioxidant,
      antiradical, and AChE inhibition effects. 

PMID- 25956826
TI  - Functional Status Outperforms Comorbidities in Predicting Acute Care Readmissions
      in Medically Complex Patients.
AB  - OBJECTIVE: To examine functional status versus medical comorbidities as
      predictors of acute care readmissions in medically complex patients. DESIGN:
      Retrospective database study. SETTING: U.S. inpatient rehabilitation facilities.
      PARTICIPANTS: Subjects included 120,957 patients in the Uniform Data System for
      Medical Rehabilitation admitted to inpatient rehabilitation facilities under the
      medically complex impairment group code between 2002 and 2011. INTERVENTIONS: A
      Basic Model based on gender and functional status was developed using logistic
      regression to predict the odds of 3-, 7-, and 30-day readmission from inpatient
      rehabilitation facilities to acute care hospitals. Functional status was measured
      by the FIM((r)) motor score. The Basic Model was compared to six other predictive
      models-three Basic Plus Models that added a comorbidity measure to the Basic
      Model and three Gender-Comorbidity Models that included only gender and a
      comorbidity measure. The three comorbidity measures used were the Elixhauser
      index, Deyo-Charlson index, and Medicare comorbidity tier system. The c-statistic
      was the primary measure of model performance. MAIN OUTCOME MEASURES: We
      investigated 3-, 7-, and 30-day readmission to acute care hospitals from
      inpatient rehabilitation facilities. RESULTS: Basic Model c-statistics predicting
      3-, 7-, and 30-day readmissions were 0.69, 0.64, and 0.65, respectively. The best
      performing Basic Plus Model (Basic+Elixhauser) c-statistics were only 0.02 better
      than the Basic Model, and the best-performing Gender-Comorbidity Model
      (Gender+Elixhauser) c-statistics were more than 0.07 worse than the Basic Model.
      CONCLUSIONS: Readmission models based on functional status consistently
      outperform models based on medical comorbidities. There is opportunity to improve
      current national readmission risk models to more accurately predict readmissions
      by incorporating functional data.

PMID- 25956828
TI  - In vivo protein targets for increased quinoprotein adduct formation in aged
      substantia nigra.
AB  - The selective vulnerability of dopaminergic neurons in the substantia nigra pars
      compacta in Parkinson's disease, a late age onset neurodegenerative disorder,
      indicates the involvement of dopamine metabolism in the pathogenesis. Dopamine
      oxidation produces dopamine o-quinone, which covalently modifies cysteinyl
      proteins forming quinoprotein adduct. Although quinoprotein formation correlates
      with increased dopaminergic neurotoxicity, the in vivo protein targets for
      quinone modification remain unclear. Using two-dimensional gel electrophoresis
      and nitroblue tetrazolium/glycinate redox-cycling staining, we compared
      quinoprotein adducts in the substantia nigra of 2- and 15-month old rats and for
      the first time identified the in vivo protein targets with increased quinone
      modification in aged substantia nigra. Interestingly, several key enzymes in
      energy metabolism and mitochondrial function were selectively modified by quinone
      during aging. In vitro analyses confirmed that two of identified enzymes, l
      lactate dehydrogenase (LDH) and malate dehydrogenase (MDH), were readily
      conjugated by dopamine o-quinone, resulting in a significant reduction in enzyme
      activity. Since the proteomic approach to detect quinoprotein adducts represents
      a single analysis comparing pools of substantia nigra from young or old rats,
      these findings need to be verified in the future. Nonetheless, our results reveal
      that the enzymatic activity of LDH and MDH can be compromised by quinone
      modification, suggesting a role of energy metabolism impairment in the selective
      vulnerability of aged substantia nigra dopaminergic neurons in Parkinson's
      disease. 

PMID- 25956830
TI  - Enzyme replacement therapy of a novel humanized mouse model of globoid cell
      leukodystrophy.
AB  - An inherited deficiency of beta-galactosylceramidase (GALC) causes the lysosomal
      storage disease globoid cell leukodystrophy (GLD). The disease is characterized
      by the accumulation of the cytotoxic metabolite psychosine
      (galactosylsphingosine), causing rapid degeneration of myelinating cells. Most
      patients suffer from the infantile form of GLD with onset of disease between 3
      and 6 months after birth and death by 2 years of age. The most widely used animal
      model of GLD, the twitcher mouse, presents with an even more rapid course of
      disease and death around 40 days of age. We have generated a novel "humanized"
      mouse model of GLD by inserting a human GALC cDNA containing an adult-onset
      patient mutation into the murine GALC gene. Humanized GALC mice exhibit
      pathological hallmarks of GLD including psychosine accumulation,
      neuroinflammation, CNS infiltration of macrophages, astrogliosis and
      demyelination. Residual GALC activities in mouse tissues are low and the mice
      display a median lifespan of 46 days. Due to the expression of the human
      transgene, the mice do not develop an immune response against rhGALC, rendering
      the animal model suitable for therapies based on human enzyme. Intravenously
      injected rhGALC was able to surmount the blood-brain barrier and was targeted to
      lysosomes of brain macrophages, astrocytes and neurons. High-dose enzyme
      replacement therapy started at postnatal day 21 reduced the elevated psychosine
      levels in the peripheral and central nervous system by 14-16%, but did not
      ameliorate neuroinflammation, demyelination and lifespan. These results may
      indicate that treatment must be started earlier before pathology occurs.

PMID- 25956829
TI  - Neonatal sensory nerve injury-induced synaptic plasticity in the trigeminal
      principal sensory nucleus.
AB  - Sensory deprivation studies in neonatal mammals, such as monocular eye closure,
      whisker trimming, and chemical blockade of the olfactory epithelium have revealed
      the importance of sensory inputs in brain wiring during distinct critical
      periods. But very few studies have paid attention to the effects of neonatal
      peripheral sensory nerve damage on synaptic wiring of the central nervous system
      (CNS) circuits. Peripheral somatosensory nerves differ from other special sensory
      afferents in that they are more prone to crush or severance because of their
      locations in the body. Unlike the visual and auditory afferents, these nerves
      show regenerative capabilities after damage. Uniquely, damage to a somatosensory
      peripheral nerve does not only block activity incoming from the sensory receptors
      but also mediates injury-induced neuro- and glial chemical signals to the brain
      through the uninjured central axons of the primary sensory neurons. These
      chemical signals can have both far more and longer lasting effects than sensory
      blockade alone. Here we review studies which focus on the consequences of
      neonatal peripheral sensory nerve damage in the principal sensory nucleus of the
      brainstem trigeminal complex. 

PMID- 25956831
TI  - Morphometric Atlas Selection for Automatic Brachial Plexus Segmentation.
AB  - PURPOSE: The purpose of this study was to determine the effects of atlas
      selection based on different morphometric parameters, on the accuracy of
      automatic brachial plexus (BP) segmentation for radiation therapy planning. The
      segmentation accuracy was measured by comparing all of the generated automatic
      segmentations with anatomically validated gold standard atlases developed using
      cadavers. METHODS AND MATERIALS: Twelve cadaver computed tomography (CT) atlases
      (3 males, 9 females; mean age: 73 years) were included in the study. One atlas
      was selected to serve as a patient, and the other 11 atlases were registered
      separately onto this "patient" using deformable image registration. This
      procedure was repeated for every atlas as a patient. Next, the Dice and Jaccard
      similarity indices and inclusion index were calculated for every registered BP
      with the original gold standard BP. In parallel, differences in several
      morphometric parameters that may influence the BP segmentation accuracy were
      measured for the different atlases. Specific brachial plexus-related CT-visible
      bony points were used to define the morphometric parameters. Subsequently,
      correlations between the similarity indices and morphometric parameters were
      calculated. RESULTS: A clear negative correlation between difference in
      protraction-retraction distance and the similarity indices was observed (mean
      Pearson correlation coefficient = -0.546). All of the other investigated Pearson
      correlation coefficients were weak. CONCLUSIONS: Differences in the shoulder
      protraction-retraction position between the atlas and the patient during planning
      CT influence the BP autosegmentation accuracy. A greater difference in the
      protraction-retraction distance between the atlas and the patient reduces the
      accuracy of the BP automatic segmentation result.

PMID- 25956832
TI  - Tumor Induction in Mice After Localized Single- or Fractionated-Dose Irradiation:
      Differences in Tumor Histotype and Genetic Susceptibility Based on Dose
      Scheduling.
AB  - PURPOSE: To investigate differences in tumor histotype, incidence, latency, and
      strain susceptibility in mice exposed to single-dose or clinically relevant,
      fractioned-dose gamma-ray radiation. METHODS AND MATERIALS: C3Hf/Kam and C57BL/6J
      mice were locally irradiated to the right hindlimb with either single large doses
      between 10 and 70 Gy or fractionated doses totaling 40 to 80 Gy delivered at 2
      Gy/d fractions, 5 d/wk, for 4 to 8 weeks. The mice were closely evaluated for
      tumor development in the irradiated field for 800 days after irradiation, and all
      tumors were characterized histologically. RESULTS: A total of 210 tumors were
      induced within the radiation field in 788 mice. An overall decrease in tumor
      incidence was observed after fractionated irradiation (16.4%) in comparison with
      single-dose irradiation (36.1%). Sarcomas were the predominant postirradiation
      tumor observed (n=201), with carcinomas occurring less frequently (n=9). The
      proportion of mice developing tumors increased significantly with total dose for
      both single-dose and fractionated schedules, and latencies were significantly
      decreased in mice exposed to larger total doses. C3Hf/Kam mice were more
      susceptible to tumor induction than C57BL/6J mice after single-dose irradiation;
      however, significant differences in tumor susceptibilities after fractionated
      radiation were not observed. For both strains of mice, osteosarcomas and
      hemangiosarcomas were significantly more common after fractionated irradiation,
      whereas fibrosarcomas and malignant fibrous histiocytomas were significantly more
      common after single-dose irradiation. CONCLUSIONS: This study investigated the
      tumorigenic effect of acute large doses in comparison with fractionated radiation
      in which both the dose and delivery schedule were similar to those used in
      clinical radiation therapy. Differences in tumor histotype after single-dose or
      fractionated radiation exposures provide novel in vivo evidence for differences
      in tumor susceptibility among stromal cell populations.

PMID- 25956833
TI  - Forgone but not forgotten: the effects of partial and full feedback in "harsh"
      and "kind" environments.
AB  - In a perfect world, the choice of any course of action would lead to a
      satisfactory outcome, and we would obtain feedback about both our chosen course
      and those we have chosen to forgo. In reality, however, we often face harsh
      environments in which we can only minimize losses, and we receive impoverished
      feedback. In these studies, we examined how decision makers dealt with these
      challenges in a simple task in which we manipulated three features of the
      decision: The outcomes from the available options were either mostly positive or
      mostly negative (kind or harsh environment); feedback was either full or partial
      (outcomes revealed for all options or only for the chosen option); and for the
      final 20 trials in a sequence, participants either chose on each trial or set an
      "advance-directive" policy. The propensity to choose the better option was
      explained by several factors: Full feedback was more beneficial in harsh than in
      kind environments; policy decisions encouraged better decisions and ameliorated
      the adverse impact of a harsh environment; and beliefs about the value of
      strategy diversification predicted switch rates and choice quality. The results
      suggest a subtle interplay between bottom-up and top-down processes: Although
      harsh environments encourage poor choices, and some decision makers choose less
      well than others, this need not imply that the decision maker has failed to
      identify the better option. 

PMID- 25956834
TI  - Lifestyle Intervention in Gastroesophageal Reflux Disease.
AB  - BACKGROUND & AIMS: Gastroesophageal reflux disease (GERD) affects up to 30% of
      adults in Western populations and is increasing in prevalence. GERD is associated
      with lifestyle factors, particularly obesity and tobacco smoking, which also
      threatens the patient's general health. GERD carries the risk of several adverse
      outcomes and there is widespread use of potent acid-inhibitors, which are
      associated with long-term adverse effects. The aim of this systematic review was
      to assess the role of lifestyle intervention in the treatment of GERD. METHODS:
      Literature searches were performed in PubMed (from 1946), EMBASE (from 1980), and
      the Cochrane Library (no start date) to October 1, 2014. Meta-analyses,
      systematic reviews, randomized clinical trials (RCTs), and prospective
      observational studies were included. RESULTS: Weight loss was followed by
      decreased time with esophageal acid exposure in 2 RCTs (from 5.6% to 3.7% and
      from 8.0% to 5.5%), and reduced reflux symptoms in prospective observational
      studies. Tobacco smoking cessation reduced reflux symptoms in normal-weight
      individuals in a large prospective cohort study (odds ratio, 5.67). In RCTs, late
      evening meals increased time with supine acid exposure compared with early meals
      (5.2% point change), and head-of-the-bed elevation decreased time with supine
      acid exposure compared with a flat position (from 21% to 15%). CONCLUSIONS:
      Weight loss and tobacco smoking cessation should be recommended to GERD patients
      who are obese and smoke, respectively. Avoiding late evening meals and head-of
      the-bed elevation is effective in nocturnal GERD.

PMID- 25956835
TI  - Incidence of Interval Colorectal Cancer Among Inflammatory Bowel Disease Patients
      Undergoing Regular Colonoscopic Surveillance.
AB  - BACKGROUND & AIMS: Surveillance is recommended for patients with long-term
      inflammatory bowel disease because they have an increased risk of colorectal
      cancer (CRC). To study the effectiveness of surveillance, we determined the
      incidence of CRC after negative findings from surveillance colonoscopies
      (interval CRC). METHODS: We collected data from 1273 patients with ulcerative
      colitis or Crohn's disease, enrolled in a surveillance program at 7 hospitals in
      The Netherlands, who underwent 4327 surveillance colonoscopies from January 1,
      2000, through January 1, 2014. Patients were followed up from their first
      surveillance colonoscopy until the last surveillance colonoscopy, colectomy, or
      CRC. Factors that might have contributed to the occurrence of CRC were
      categorized as inadequate procedures (ie, inadequate bowel preparation),
      inadequate surveillance (CRC occurring outside the appropriate surveillance
      interval), or inadequate management of dysplasia (CRC diagnosed in the same
      colonic segment as a previous diagnosis of dysplasia). The remaining CRC cases
      were classified as true interval CRCs. RESULTS: CRC was diagnosed in 17 patients
      (1.3%), with an incidence of 2.5 per 1000 years of follow-up evaluation. Factors
      that might account for the occurrence of CRC were identified in 12 patients
      (70%). These were inadequate colonoscopies in 4 patients (24%), inadequate
      surveillance intervals in 9 patients (53%), and inadequate management of
      dysplasia in 2 patients (12%). The remaining 5 cases of CRC (30%) were classified
      as true interval CRCs. CONCLUSIONS: In a retrospective analysis of patients with
      inflammatory bowel disease participating in a surveillance program, the incidence
      of CRC was only 1%, which supports the implementation of longer surveillance
      intervals. However, the fact that 30% of CRC cases were interval cancers
      indicates the need for variable surveillance intervals based on risk factors for
      CRC.

PMID- 25956836
TI  - Features of Patients With Crohn's Disease and Hidradenitis Suppurativa.
AB  - BACKGROUND & AIMS: There have been reports of an association between Crohn's
      disease and hidradenitis suppurativa, a chronic, relapsing, inflammatory
      condition of the skin. We investigated features of hidradenitis suppurativa in
      patients with Crohn's disease by analyzing clinical data and performing a
      literature review. METHODS: We performed a retrospective study by using
      information from the Mount Sinai Medical Center database from 2003 through 2013;
      International Classification of Diseases, 9th Revision codes were used to
      identify patients who had both Crohn's disease and hidradenitis suppurativa. We
      identified a total of 18 patients with inflammatory bowel disease (15 with
      Crohn's disease, 3 with ulcerative colitis) and hidradenitis suppurativa. We also
      performed a systematic search for publications listed in PubMed through December
      2013. RESULTS: We identified 15 patients with Crohn's disease and hidradenitis
      suppurativa who met the inclusion criteria (11 women, 4 men). Nine patients were
      black, 5 were white, and 1 was Asian. Regions most affected by hidradenitis
      suppurativa included the axilla (53%), inguinal region (47%), and perianal region
      (73%). Seven patients had colonic Crohn's disease, and 8 had ileocolonic Crohn's
      disease; 10 patients had perianal disease. Fourteen patients received medical
      treatment for hidradenitis suppurativa and for Crohn's disease. Twelve patients
      were treated with tumor necrosis factor inhibitors for Crohn's disease (11
      received infliximab and 4 received adalimumab). Nine patients required dose
      escalation; 11 responded to tumor necrosis factor inhibitors, and 8 required
      surgery. Four patients were treated with tumor necrosis factor inhibitors for
      hidradenitis suppurativa (all with infliximab). Three required a dose escalation;
      4 responded to tumor necrosis factor inhibitors, and 3 required surgery.
      CONCLUSIONS: Crohn's disease and hidradenitis suppurativa are severe inflammatory
      conditions that can develop in the same patient. They frequently require
      increased medical and surgical therapy.

PMID- 25956837
TI  - Effects of Comorbidities on Outcomes of Patients With Intraductal Papillary
      Mucinous Neoplasms.
AB  - BACKGROUND & AIMS: Intraductal papillary mucinous neoplasms (IPMNs) of the
      pancreas occur mostly in older individuals. Individual life expectancy and risk
      of death from other factors must be carefully considered in analyzing the risks
      that IPMNs pose. We investigated whether there is a subset of patients with IPMNs
      and a high risk of dying from other causes who would not benefit from pancreatic
      surgery. METHODS: We collected data from 725 patients at Massachusetts General
      Hospital who underwent resection or have been under observation for IPMNs from
      1992 through 2012. Comorbidities were classified according to the age-adjusted
      Charlson comorbidity index (CACI). Causes of death were recorded, and survival
      data were analyzed by the Kaplan-Meier method. RESULTS: The patients' median CACI
      score was 3; 10% of patients had CACI of 7 or more. Of the entire cohort, 55%
      underwent resection, and the remaining 45% have been under observation. After a
      median follow-up period of 5 years, 177 patients died (24%, 55% of deaths within
      5 years of diagnosis); 78% of deaths were not related to IPMNs. The median
      survival time for all patients with CACI score of 7 or more was 43 months.
      Multivariate regression analysis revealed that the chance of non-IPMN-related
      death within 3 years of diagnosis is 11-fold higher for patients with CACI score
      of 7 or more than for patients with lower scores. CONCLUSIONS: The CACI can be
      used to identify patients with a high risk of death from factors other than IPMNs
      within a few years after diagnosis. These patients are therefore not likely to
      benefit from further IPMN observation or pancreatic resection.

PMID- 25956838
TI  - Water Exchange Is the Least Painful Colonoscope Insertion Technique and Increases
      Completion of Unsedated Colonoscopy.
AB  - BACKGROUND & AIMS: Unsedated colonoscopy is acceptable for diagnostic,
      surveillance, and screening indications worldwide. However, insertion of the
      colonoscope can be painful; it is not clear which technique is least painful and
      thereby increases the likelihood of colonoscopy completion. We performed a head
      to-head comparison of air insufflation (AI), carbon dioxide (CO2) insufflation,
      water immersion (WI), and water exchange (WE) to determine which combination of
      insertion techniques produces the least amount of pain. METHODS: In a patient
      blinded prospective trial, 624 subjects were assigned randomly to groups that
      underwent colonoscopy with AI-AI, CO2-CO2, WI-AI, WE-AI, WI-CO2, or WE-CO2
      insertion and withdrawal techniques, including on-demand sedation, at the St.
      Barbara Hospital (Iglesias, Italy) or the Vitkovice Hospital (Ostrava, Czech
      Republic), from October 2013 through June 2014. The primary outcome was real-time
      maximum insertion pain (0 = none, 10 = worst), recorded by an unblinded nurse
      assistant. At discharge, a blinded observer recorded the recalled maximum
      insertion pain and patients' and investigators' guesses about method or gas used.
      RESULTS: Patients and investigators correctly guessed the method used for fewer
      than 44% of procedures, confirming adequate blinding. The correlation between
      real-time and recalled maximum insertion pain (r = 0.9; P < .0005) confirmed
      internal validation of the primary outcome. The WE group had the lowest scores:
      mean pain values were 5.2 for AI-AI (95% confidence interval [CI], 4.6-5.8), 4.9
      for CO2-CO2 (95% CI, 4.3-5.4), 4.3 for WI-CO2 (95% CI, 3.8-4.9), 4.0 for WI-AI
      (95% CI, 3.5-4.5), 3.1 for WE-CO2 (95% CI, 2.7-3.4), and 3.1 for WE-AI (95% CI,
      2.7-3.6) (P < .0005). The highest proportions of patients completing unsedated
      colonoscopy were in the WE groups. WE groups also had significantly better colon
      cleanliness, particularly in the transverse and right colon (P < .0005). One
      limitation of the study was that colonoscopists and assistants were not blinded
      to water-aided insertion methods. CONCLUSIONS: In a prospective study of
      colonoscopy insertion methods, CO2 insufflation did not reduce real-time maximum
      insertion pain. Compared with AI or CO2, WI and WE reduced insertion pain. The
      least painful technique was WE, which significantly increased completion of
      unsedated colonoscopy and bowel cleanliness without prolonging insertion time.
      ClinicalTrials.gov number: NCT01954862.

PMID- 25956839
TI  - Investigation of Dysphagia After Antireflux Surgery by High-resolution Manometry:
      Impact of Multiple Water Swallows and a Solid Test Meal on Diagnosis, Management,
      and Clinical Outcome.
AB  - BACKGROUND & AIMS: Management of patients with dysphagia, regurgitation, and
      related symptoms after antireflux surgery is challenging. This prospective, case
      control study tested the hypothesis that compared with standard high-resolution
      manometry (HRM) with single water swallows (SWS), adding multiple water swallows
      (MWS) and a solid test meal increases diagnostic yield and clinical impact of
      physiological investigations. METHODS: Fifty-seven symptomatic and 12
      asymptomatic patients underwent HRM with SWS, MWS, and a solid test meal.
      Dysphagia and reflux were assessed by validated questionnaires. Diagnostic yield
      of standard and full HRM studies with 24-hour pH-impedance monitoring was
      compared. Pneumatic dilatation was performed for outlet obstruction on HRM
      studies. Clinical outcome was assessed by questionnaires and an analogue scale
      with "satisfactory" defined as at least 40% symptom improvement requiring no
      further treatment. RESULTS: Postoperative esophagogastric junction pressure was
      similar in all groups. Abnormal esophagogastric junction morphology (double high
      pressure band) was more common in symptomatic than in control patients (13 of 57
      vs 0 of 12, P = .004). Diagnostic yield of HRM was 11 (19%), 11 (19%), and 33 of
      57 (58%), with SWS, MWS, and solids, respectively (P < .001); it was greatest for
      solids in patients with dysphagia (19 of 27, 70%). Outlet obstruction was present
      in 4 (7%), 11 (19%), and 15 of 57 patients (26%) with SWS, MWS, and solids,
      respectively (P < .009). No asymptomatic control had clinically relevant
      dysfunction on solid swallows. Dilatation was performed in 12 of 15 patients with
      outlet obstruction during the test meal. Symptom response was satisfactory, good,
      or excellent in 7 of 12 (58%) with no serious complications. CONCLUSIONS: The
      addition of MWS and a solid test meal increases the diagnostic yield of HRM
      studies in patients with symptoms after fundoplication and identifies additional
      patients with outlet obstruction who benefit from endoscopic dilatation.

PMID- 25956841
TI  - Sex Hormones, Sex Hormone-Binding Globulin, and Liver Fat: Which Came First, the
      Chicken or the Egg?

PMID- 25956840
TI  - Vaccination and Risk for Developing Inflammatory Bowel Disease: A Meta-Analysis
      of Case-Control and Cohort Studies.
AB  - BACKGROUND & AIMS: Environmental factors may play a key role in the pathogenesis
      of inflammatory bowel disease (IBD). Whether vaccination is associated causally
      with IBD is controversial. We performed a meta-analysis of case-control and
      cohort studies on the association between vaccination and the risk for IBD.
      METHODS: Studies and abstracts investigating the relationship between vaccination
      and subsequent risk for developing IBD were reviewed. Childhood or adult
      immunizations with any vaccine type, at any dose, and with any vaccine schedule
      were used as inclusion criteria. RESULTS: Eleven studies were included in the
      systematic review and meta-analysis: 8 case-control studies and 3 cohort studies.
      Studied vaccines were bacille Calmette-Guerin), vaccines against diphtheria,
      tetanus, smallpox, poliomyelitis, pertussis, H1N1, measles, rubella, mumps, and
      the combined measles, mumps, and rubella vaccine. Only a few details about
      vaccine type or route of administration were found in studies. Overall, there was
      no association between childhood immunization and risk for developing IBD:
      bacille Calmette-Guerin, relative risk (RR) of 1.04 (95% confidence interval
      [CI], 0.78-1.38), diphtheria, RR of 1.24 (95% CI, 0.80-1.94), tetanus, RR of 1.27
      (95% CI, 0.77-2.08), smallpox, RR of 1.08 (95% CI, 0.70-1.67), poliomyelitis, RR
      of 1.79 (95% CI, 0.88-3.66), an measles containing vaccines, RR of 1.33 (95% CI,
      0.31-5.80) in cohort studies, and RR of 0.85 (95% CI, 0.60-1.20) in case-control
      studies. Subgroup analysis for Crohn's disease (CD) and ulcerative colitis (UC)
      found an association between the poliomyelitis vaccine and risk for developing CD
      (RR, 2.28; 95% CI, 1.12-4.63) or UC (RR, 3.48; 95% CI, 1.2-9.71). The RR of
      developing IBD after H1N1 vaccination was 1.13 (95% CI, 0.97-1.32). CONCLUSIONS:
      Results of this meta-analysis show no evidence supporting an association between
      childhood immunization or H1N1 vaccination in adults and risk of developing IBD.
      The association between the poliomyelitis vaccine and the risk for CD or UC
      should be analyzed with caution because of study heterogeneity.

PMID- 25956842
TI  - Identification of circulating MicroRNAs as novel potential biomarkers for
      hepatocellular carcinoma detection: a systematic review and meta-analysis.
AB  - BACKGROUND: MicroRNAs (miRNAs) in body fluids such as serum and plasma can be
      stably detected and used as potential biomarkers in hepatocellular carcinoma
      (HCC) diagnosis. OBJECTIVE: To systematically evaluate circulating miRNAs from
      HCC expression profiling studies and to determine miRNA biomarkers for HCC
      detection. METHODS: A systematic review and meta-analysis of published studies
      were carried out for comparing the circulating miRNA expressions between HCC
      patients and healthy people, hepatitis, or cirrhosis patients. A miRNA ranking
      system that considered the number of comparisons in agreement and total number of
      samples was used. Then the summary receiver-operating characteristic curve (sROC)
      results of the top miRNAs were combined to further evaluate their diagnostic
      value using Meta-disc 1.4. RESULTS: In the 17 included studies, three circulating
      miRNAs (miR-21, miR-122, and miR-223) were repeatedly reported three times or
      more in both HCC patients vs. healthy controls and vs. other hepatitis or
      cirrhosis patients. In further analysis, the area under curve (AUC) of sROC for
      miR-21, miR-122 and miR-223 in discriminating HCC patients from healthy people
      are 0.9293, 0.8128, and 0.8597, respectively. CONCLUSIONS: Circulating miR-21 has
      highest level of diagnostic efficiency among three miRNAs candidate biomarkers
      (miR-21, miR-122, and miR-223) for detection of HCC.

PMID- 25956843
TI  - Aerosolised liposomal amphotericin B to prevent aspergillosis in acute myeloid
      leukaemia: Efficacy and cost effectiveness in real-life.
AB  - Chemotherapy-induced neutropenia can be complicated by invasive pulmonary
      aspergillosis (IPA). In 2008, liposomal amphotericin B (L-AmB) inhalation was
      shown to prevent IPA in a placebo-controlled trial. Patients with acute myeloid
      leukaemia (AML) are the subset of haematology patients at high risk for IPA. In
      2008, L-AmB inhalation prophylaxis became the standard of care for all AML
      patients in Erasmus MC. In this study, the efficacy and cost effectiveness of L
      AmB inhalation were evaluated in a prospective cohort of AML patients. In total,
      127 consecutive AML patients received chemotherapy and prophylactically inhaled L
      AmB during their first and second chemotherapy cycles; 108 patients treated for
      AML at the same sites from 2005-2008 served as controls. A standardised
      diagnostic protocol was used and probable/proven IPA served as the primary
      endpoint. Diagnostic and therapeutic costs were also comprehensively analysed and
      compared. A significant decrease in probable/proven IPA in the L-AmB inhalation
      group was observed (L-AmB 9.5% vs. controls 23.4%; P=0.0064). Systemic antifungal
      therapy given at any time during the entire AML therapy decreased from 52.8% to
      29.9%. Per-patient equipment and drug costs for L-AmB inhalation (1292 ?/patient)
      were more than compensated for by a decrease in costs for diagnostics and
      therapeutic voriconazole use (-1816 ?/patient). No serious adverse events related
      to L-AmB inhalation were observed. In an unselected AML patient group, L-AmB
      inhalation resulted in a significant and substantial decrease in IPA and was cost
      saving. Now that azole resistance is more frequent, non-azole-based prophylaxis
      may become an attractive strategy. 

PMID- 25956844
TI  - Ceftazidime/avibactam tested against Gram-negative bacteria from intensive care
      unit (ICU) and non-ICU patients, including those with ventilator-associated
      pneumonia.
AB  - Ceftazidime/avibactam consists of ceftazidime combined with the novel non-beta
      lactam beta-lactamase inhibitor avibactam, which inhibits Ambler classes A, C and
      some D enzymes. Clinical isolates were collected from 71 US medical centres in
      2012-2013 and were tested for susceptibility at a central laboratory by reference
      broth microdilution methods. Results for 4381 bacterial isolates from intensive
      care unit (ICU) patients as well as those from ventilator-associated pneumonia
      (VAP) (n=435) were analysed and compared with those of 14 483 organisms from non
      ICU patients. beta-Lactamase-encoding genes were evaluated for 966
      Enterobacteriaceae by a microarray-based assay. Ceftazidime/avibactam was active
      against 99.8/100.0% of Enterobacteriaceae (MIC90, 0.25/0.25mg/L) from ICU/non-ICU
      patients (2948/10,872 strains), including isolates from VAP (99.1%), multidrug
      resistant (MDR) strains (99.3%), extensively drug-resistant (XDR) strains (96.5%)
      and meropenem-non-susceptible strains (98.0%), at MICs of <=8mg/L. Against
      Enterobacteriaceae, susceptibility rates for ceftazidime, piperacillin/tazobactam
      and meropenem (ICU/non-ICU) were 86.1/91.8%, 88.0/94.3% and 97.8/99.2%,
      respectively. Meropenem was active against 75.1/85.4% of MDR Enterobacteriaceae
      and 8.1/27.1% of XDR Enterobacteriaceae from ICU/non-ICU patients. When tested
      against Pseudomonas aeruginosa, ceftazidime/avibactam inhibited 95.6/97.5% of
      isolates from ICU/non-ICU (842/2240 isolates), 97.3% of isolates from VAP, 80.7%
      of ceftazidime-non-susceptible and 80.7% of MDR isolates at <=8mg/L.
      Susceptibility rates for P. aeruginosa from ICU/non-ICU were 77.7/86.9% for
      ceftazidime, 71.2/82.2% for piperacillin/tazobactam and 76.6/84.7% for meropenem.
      In summary, lower susceptibility rates were observed among ICU compared with non
      ICU isolates. Ceftazidime/avibactam exhibited potent activity against a large
      collection of Gram-negative organisms from ICU and non-ICU patients and provided
      greater coverage than currently available beta-lactams. 

PMID- 25956845
TI  - Editorial - May 2015.

PMID- 25956847
TI  - Growth of rat parotid glands is inhibited by liquid diet feeding.
AB  - This study investigated how liquid diet feeding affects the growth of parotid
      glands. We weaned 21-day-old rats and thereafter fed them a pellet diet (control
      group) or a liquid diet (experimental group) for 0, 1, 2, 4, or 8 weeks. Their
      parotid glands were excised, weighed, examined, and tested for 5-bromo-2'
      deoxyuridine (BrdU) and cleaved caspase-3 (Casp-3) as markers of proliferation
      and apoptosis, respectively. Parotid gland weights were consistently smaller in
      experimental animals than in controls. Morphometrical analysis showed that
      control group acinar cells increased in area during the experiment, but
      experimental group acinar cells were almost unchanged. Labeling indices of BrdU
      in acinar cells in both groups declined during the experiment, but were
      consistently lower in the experimental group than in controls. Casp-3-positive
      acinar cells were rare in both groups, which consistently express significantly
      similar Casp-3 levels. Ultrastructurally, terminal portions of the experimental
      parotid glands consisted of a few acinar cells that were smaller than those in
      controls. Control acinar cells showed mitotic figures within short experimental
      periods, but not in experimental glands. These observations indicate that liquid
      diet feeding inhibits growth of parotid glands in growing rats through
      suppression of growth and proliferation of individual acinar cells, but not
      through apoptosis. 

PMID- 25956846
TI  - Towards the computational design of protein post-translational regulation.
AB  - Protein post-translational modifications (PTMs) are a fast and versatility
      mechanism used by the cell to regulate the function of proteins in response to
      changing conditions. PTMs can alter the activity of proteins by allosteric
      regulation or by controlling protein interactions, localization and abundance.
      Recent advances in proteomics have revealed the extent of regulation by PTMs and
      the different mechanisms used in nature to exert control over protein function
      via PTMs. These developments can serve as the foundation for the rational design
      of protein regulation. Here we review the advances in methods to determine the
      function of PTMs, protein allosteric control and examples of rational design of
      PTM regulation. These advances create an opportunity to move synthetic biology
      forward by making use of a level of regulation that is of yet unexplored.

PMID- 25956848
TI  - Intracellular diglycerides in relation to glycaemic control in the myocardium: A
      pilot study in humans.
AB  - AIM: Intramyocellular diglycerides have been implicated in the development of
      insulin resistance in skeletal muscle. In the myocardium, excess lipid storage
      may also contribute to the appearance of diabetic cardiomyopathy, while
      diglycerides may have certain cardio-protective functions. However, little is
      known on intracellular diglyceride accumulation in the human heart. We aimed to
      determine diglyceride accumulation in the human myocardium in relation to
      diabetes status. METHODS: Six diabetic and six non-diabetic aged human subjects
      undergoing by-pass surgery participated in the study. Subjects were matched for
      age and body mass index. Intracellular diglyceride levels were measured in heart
      biopsy samples. Additional samples were taken from pectoralis major muscle that
      served as control. Whole body glycaemic control was assessed as the percent
      glycated haemoglobin. RESULTS: Intracellular diglycerides were significantly
      higher in the myocardium compared to pectoralis major (P<0.05). Although not
      statistically significant, diabetic subjects tended to accumulate smaller amounts
      of diglycerides compared to non-diabetic subjects in the myocardium. A linear
      negative correlation was observed between myocardial diglycerides and glycaemic
      control (r=0.632, P<0.05). CONCLUSIONS: Our data suggest that poor glycaemic
      control and diabetes may be associated with a defective accumulation of
      myocardial diglycerides, possibly blunting intracellular processes and
      contributing to the development of cardiomyopathy.

PMID- 25956849
TI  - Ceftaroline fosamil for the treatment of hospital-acquired pneumonia and
      ventilator-associated pneumonia.
AB  - OBJECTIVES: Ceftaroline fosamil is a novel cephalosporin with bactericidal
      activity against common pathogens associated with hospital-acquired pneumonia
      (HAP) and ventilator-associated pneumonia (VAP). Ceftaroline is inactive against
      extended-spectrum beta-lactamase-producing or AmpC-overexpressing
      Enterobacteriaceae and has limited activity against Pseudomonas aeruginosa.
      CAPTURE is a multicenter, retrospective study designed to collect information on
      contemporary clinical use of ceftaroline fosamil in the USA. Data on off-label
      use of ceftaroline fosamil for the treatment of patients with HAP/VAP between
      September 2013 and March 2014 are presented. METHODS: Data were collected at
      participating study centers by randomized selection and review of patients'
      charts, and included patients' demographics, disease characteristics, pathogens
      isolated, antibiotic treatment and clinical outcomes. Patients receiving at least
      four consecutive doses of ceftaroline fosamil, with data available for
      determination of clinical cure, comprised the evaluable population. Clinical
      success was defined as either clinical cure with no further need for antibiotics
      treatment, or clinical improvement with a switch to another antibiotic. RESULTS:
      A total of 40 patients were evaluated: 27 with HAP and 13 with VAP. Demographics
      for patients with HAP and VAP were similar (59% male, mean age of 63 years and
      54% male, mean age of 58 years, respectively). The clinical success rates were
      75% overall, 82% in patients with HAP and 62% in patients with VAP. Clinical
      success rates for patients with methicillin-resistant Staphylococcus aureus
      (MRSA) isolated were 58% in patients with HAP and 57% in patients with VAP.
      Ceftaroline fosamil was used as a second-line therapy in majority of patients
      (85%) with clinical success rates of 79% similar to the published literature.
      CONCLUSION: The CAPTURE study data support further evaluation of ceftaroline
      fosamil as an effective treatment option for HAP and VAP when a ceftaroline
      susceptible etiologic pathogen is identified, including MRSA, or as a concurrent
      therapy when resistant Gram-negative pathogens are suspected.

PMID- 25956850
TI  - Three-dimensional, soft neotissue arrays as high throughput platforms for the
      interrogation of engineered tissue environments.
AB  - Local signals from tissue-specific extracellular matrix (ECM) microenvironments,
      including matrix adhesive ligand, mechanical elasticity and micro-scale geometry,
      are known to instruct a variety of stem cell differentiation processes. Likewise,
      these signals converge to provide multifaceted, mechanochemical cues for highly
      specific tissue morphogenesis or regeneration. Despite accumulated knowledge
      about the individual and combined roles of various mechanochemical ECM signals in
      stem cell activities on 2-dimensional matrices, the understandings of
      morphogenetic or regenerative 3-dimenstional tissue microenvironments remain very
      limited. To that end, we established high-throughput platforms based on soft,
      fibrous matrices with various combinatorial ECM proteins meanwhile highly-tunable
      in elasticity and 3-dimensional geometry. To demonstrate the utility of our
      platform, we evaluated 64 unique combinations of 6 ECM proteins (collagen I,
      collagen III, collagen IV, laminin, fibronectin, and elastin) on the adhesion,
      spreading and fate commitment of mesenchymal stem cell (MSCs) under two substrate
      stiffness (4.6 kPa, 20 kPa). Using this technique, we identified several
      neotissue microenvironments supporting MSC adhesion, spreading and
      differentiation toward early vascular lineages. Manipulation of the matrix
      properties, such as elasticity and geometry, in concert with ECM proteins will
      permit the investigation of multiple and distinct MSC environments. This paper
      demonstrates the practical application of high through-put technology to
      facilitate the screening of a variety of engineered microenvironments with the
      aim to instruct stem cell differentiation.

PMID- 25956851
TI  - Injectable microcryogels reinforced alginate encapsulation of mesenchymal stromal
      cells for leak-proof delivery and alleviation of canine disc degeneration.
AB  - In situ crosslinked thermo-responsive hydrogel applied for minimally invasive
      treatment of intervertebral disc degeneration (IVDD) may not prevent extrusion of
      cell suspension from injection site due to high internal pressure of
      intervertebral disc (IVD), causing treatment failure or osteophyte formation. In
      this study, mesenchymal stromal cells (MSCs) were encapsulated in alginate
      precursor and loaded into previously developed macroporous PGEDA-derived
      microcryogels (PMs) to form three-dimensional (3D) microscale cellular niches,
      enabling non-thermo-responsive alginate hydrogel to be injectable. The PMs
      reinforced alginate hydrogel showed superior elasticity compared to alginate
      hydrogel alone and could well protect encapsulated cells through injection.
      Chondrogenic committed MSCs in the injectable microniches expressed higher level
      of nucleus pulposus (NP) cell markers compared to 2D cultured cells. In an ex
      vivo organ culture model, injection of MSCs-laden PMs into NP tissue prevented
      cell leakage, improved cell retention and survival compared to free cell
      injection. In canine IVDD models, alleviated degeneration was observed in MSCs
      laden PMs treated group after six months which was superior to other treated
      groups. Our results provide in-depth demonstration of injectable alginate
      hydrogel reinforced by PMs as a leak-proof cell delivery system for augmented
      regenerative therapy of IVDD in canine models.

PMID- 25956853
TI  - Targeted delivery of CXCR4-siRNA by scFv for HER2(+) breast cancer therapy.
AB  - Therapeutics based on short interfering RNAs (siRNAs) have great potential to
      treat human diseases. However, the clinical application of siRNAs has been
      limited by their poor intracellular uptake, low serum stability, and inability to
      target specific cells. In this study, we addressed this lack of specificity by
      synthesizing a molecularly targeted CXCR4-siRNA (CXCR4si) for the treatment of
      HER2(+) breast cancers using a HER2-scFv-arginine nonamer peptide fusion protein
      (e23sFv-9R) as an siRNA carrier. The e23sFv-9R binding siRNA is able to
      specifically deliver the siRNA to HER2(+) breast cancer cells and concentrate and
      persist in orthotopic HER2(+) breast cancer xenografts for at least 36 h. CXCR4si
      delivered by e23sFv-9R inhibited CXCR4 gene expression, reduced proliferation and
      metastasis and induced apoptosis in the HER2(+) breast cancer BT-474 cell line in
      vitro. Moreover, the systemic delivery of CXCR4si by e23sFv-9R is able to
      suppress tumor growth, reduce metastasis and prolong survival in mice bearing
      HER2(+) xenografts. This approach causes no systemic toxicity and does not
      activate the innate immune response, suggesting that a fusion protein carrying
      CXCR4si shows promise in the treatment of HER2-overexpressing breast cancer.

PMID- 25956854
TI  - Synthesis of a novel, sequentially active-targeted drug delivery nanoplatform for
      breast cancer therapy.
AB  - Breast cancer is the leading cause of cancer deaths among women. Paclitaxel
      (PTX), an important breast cancer medicine, exhibits reduced bioavailability and
      therapeutic index due to high hydrophobicity and indiscriminate cytotoxicity. PTX
      encapsulation in one-level active targeting overcomes such barriers, but enhances
      toxicity to normal tissues with cancer-similar expression profiles. This research
      attempted to overcome this challenge by increasing selectivity of cancer cell
      targeting while maintaining an ability to overcome traditional pharmacological
      barriers. Thus, a multi-core, multi-targeting construct for tumor specific
      delivery of PTX was fabricated with (i) an inner-core prodrug targeting the
      cancer-overexpressed cathepsin B through a cathepsin B-cleavable tetrapeptide
      that conjugates PTX to a poly(amidoamine) dendrimer, and (ii) the encapsulation
      of this prodrug (PGD) in an outer core of a RES-evading, folate receptor (FR)
      targeting liposome. Compared to traditional FR-targeting PTX liposomes, this
      sequentially active-targeted dendrosome demonstrated better prodrug retention, an
      increased cytotoxicity to cancer cells (latter being true when FR and cathepsin B
      activities were both at moderate-to-high levels) and higher tumor reduction. This
      research may eventually evolve a product platform with reduced systemic toxicity
      inherent with traditional chemotherapy and localized toxicity inherent to single
      target nanoplatforms, thereby allowing for better tolerance of higher therapeutic
      load in advanced disease states. 

PMID- 25956855
TI  - Role of Zscan4 in secondary murine iPSC derivation mediated by protein extracts
      of ESC or iPSC.
AB  - Previously, we found that the delivery of mouse ES (mES) cell-derived proteins to
      adult fibroblasts enables the full reprogramming of these cells, converting them
      to mouse pluripotent stem cells (protein-iPS cells) without transduction of
      defined factors. During reprogramming, global gene expression and epigenetic
      status such as DNA methylation and histone modifications convert from somatic to
      ES-equivalent status. mES cell extract-derived iPS cells are biologically and
      functionally indistinguishable from mES cells in its potential in differentiation
      both in vitro and in vivo. Furthermore, these cells show complete developmental
      potency. However, the efficiency of generating iPS by treatment with extract from
      mES cells is still low. In this report, we demonstrated that protein extracts of
      mouse iPS cells that were previously generated by mES cell extract treatment were
      able to reprogram somatic cells to become ES-like cells (secondary protein-iPS
      cells). We confirmed that fetal animals (E12.5) could be derived from these
      cells. Surprisingly, the efficiency of forming Oct4-positive colonies was
      remarkably improved by treatment of somatic cells with mouse iPS cell extract in
      comparison to treatment with mES cell extract. By screening the genes
      differentially expressed between mouse iPS and mES cells, Zscan4, which is known
      to enhance telomere elongation and stabilize genomic DNA, was identified as a
      strong candidate to promote efficiency of reprogramming. Interestingly, treatment
      with protein extracted from mES cells overexpressing Zscan4 enhanced formation of
      Oct4-positive colonies. Our results provide an efficient and safe strategy for
      reprogramming somatic cells by using mouse iPS cell extract. Zscan4 might be a
      key molecule involved in the demonstrated improvement of reprogramming
      efficiency.

PMID- 25956852
TI  - Docetaxel-carboxymethylcellulose nanoparticles target cells via a SPARC and
      albumin dependent mechanism.
AB  - Cellax, a polymer-docetaxel (DTX) conjugate that self-assembled into 120 nm
      particles, displayed significant enhancements in safety and efficacy over native
      DTX across a number of primary and metastatic tumor models. Despite these
      exciting preclinical data, the underlying mechanism of delivery of Cellax remains
      elusive. Herein, we demonstrated that serum albumin efficiently adsorbed onto the
      Cellax particles with a 4-fold increased avidity compared to native DTX, and the
      uptake of Cellax by cells was primarily driven by an albumin and SPARC (secreted
      protein acidic and rich in cysteine, an albumin binder) dependent internalization
      mechanism. In the SPARC-positive cells, a >2-fold increase in cellular
      internalization of Cellax was observed in the presence of albumin. In the SPARC
      negative cells, no difference in Cellax internalization was observed in the
      presence or absence of albumin. Evaluation of the internalization mechanism using
      endocytotic inhibitors revealed that Cellax was internalized predominantly via a
      clathrin-mediated endocytotic mechanism. Upon internalization, it was
      demonstrated that Cellax was entrapped within the endo-lysosomal and
      autophagosomal compartments. Analysis of the tumor SPARC level with tumor growth
      inhibition of Cellax in a panel of tumor models revealed a positive and linear
      correlation (R(2) > 0.9). Thus, this albumin and SPARC-dependent pathway for
      Cellax delivery to tumors was confirmed both in vitro and in vivo.

PMID- 25956856
TI  - Functional G894T (rs1799983) polymorphism and intron-4 VNTR variant of nitric
      oxide synthase (NOS3) gene are susceptibility biomarkers of obesity among
      Tunisians.
AB  - OBJECTIVE: The endothelial nitric oxide synthase (NOS3) has been shown to play a
      role in the modulation of lipolysis. The goal of this study was to examine the
      impact of the G894T (rs1799983) and a 27 bp variable number of tandem repeats
      (VNTR 4a/b) of NOS3 gene on obesity in a sample of the Tunisian population.
      RESEARCH METHODS AND PROCEDURES: The study included 211 normal weight subjects
      and 183 obese patients. NOS3 G894T and 4a/b variants were determined by PCR
      analysis and examined for association with obesity-related traits. The effect of
      obesity on forearm skin blood flow (FSBF) response to acetylcholine, an
      endothelium-dependent vasodilator was determined by laser Doppler iontophoresis.
      RESULTS: In case-control studies, both G894T and 4a/b variants were associated
      with obesity. A significantly increased risk of obesity was found with the
      NOS3(G894T) TT genotype (OR:2.62, P=0.04). This association remains significant
      after adjustments for age and gender (OR: 2.93, P=0.03). A higher risk was also
      observed for carriers of the G894T allele (OR: 1.72, P=0.001). Stratified
      analysis by gender revealed that obese men (but not women) had significantly
      higher frequency of TT genotypes compared to controls (9.9% vs. 2.9%, P=0.01).
      Carriers of the 4b allele presented a significantly higher risk of obesity than
      non-carriers even after adjustments for age and gender (OR (95%CI): 1.72 (1.16
      2.56), P=0.004). Correlations with anthropometric parameters revealed that
      carriers of TT and bb genotypes had significantly higher body mass index compared
      to those homozygous for the G and a alleles (P=0.0004). CONCLUSION: This study
      provides the first evidence for the association of G894T and 4a/b variants with
      body mass index and the risk of obesity in Tunisians. These polymorphisms did not
      exhibit, however any significant association with both metabolic traits and
      vascular function.

PMID- 25956857
TI  - Predictive validity of the post-enrolment English language assessment tool for
      commencing undergraduate nursing students.
AB  - BACKGROUND: Nursing students with English as an additional language (EAL) may
      underperform academically. The post-enrolment English language assessment (PELA)
      is used in literacy support, but its predictive validity in identifying those at
      risk of underperformance remains unknown. OBJECTIVES: To validate a PELA, as a
      predictor of academic performance. DESIGN: Prospective survey design. SETTING:
      The study was conducted at a university located in culturally and linguistically
      diverse areas of western Sydney, Australia. PARTICIPANTS: Commencing
      undergraduate nursing students who were Australian-born (n=1323, 49.6%) and born
      outside of Australia (n=1346, 50.4%) were recruited for this study. The 2669 (67%
      of 3957) participants provided consent and completed a first year nursing unit
      that focussed on developing literacy skills. METHOD: Between 2010 and 2013,
      commencing students completed the PELA and English language acculturation scale
      (ELAS), a previously validated instrument. The grading levels of the PELA tool
      were: Level 1 (proficient), Level 2 (borderline), and Level 3 (poor, and
      requiring additional support). RESULTS: Participants with a PELA Level 2 or 3
      were more likely to be: a) non-Australian-born (chi(2): 520.6, df: 2, p<0.001);
      b) spoke a language other than English at home (chi(2): 490.2, df: 2, p<0.001);
      and c) an international student (chi(2): 225.6, df: 2, p<0.001). There was an
      inverse relationship between participants' ELAS scores and PELA levels (r=-0.52,
      p<0.001), and those graded as 'proficient' with a PELA Level 1 were more likely
      to obtain higher scores in their: i) unit essay assessment (chi(2): 40.2, df: 2,
      p<0.001); ii) final unit mark (chi(2): 218.6, df: 2, p<0.001), and attain a
      higher GPA (chi(2): 100.8, df: 2, p<0.001). CONCLUSION: The PELA is a useful
      screening tool in identifying commencing nursing students who are at risk of
      academic underachievement.

PMID- 25956858
TI  - Identifying student knowledge and perception of what is valuable to professional
      practice: A mixed method study.
AB  - BACKGROUND: Bachelor of Nursing programmes are designed to prepare Registered
      Nurses for professional practice. The Bachelor of Nursing curriculum under
      discussion was shaped by the conceptual framework of primary health care
      philosophy, including themes of social justice, Indigenous health, caring
      philosophy, and the advancement of the discipline through research, scholarship
      and application of nursing knowledge and evidence-based practice. OBJECTIVES:
      This study was designed to identify what students and graduates found valuable in
      a Bachelor of Nursing curriculum conceptual framework and what value they placed
      on a conceptual framework and underpinning themes. DESIGN: A small study was
      designed to identify the student perceptions of themes which may be valuable to
      the new curriculum of the Bachelor of Nursing. A mixed methodology was selected
      as being appropriate to allow students to indicate the value that previous and
      completing students placed on each of these items and to explore their
      perceptions. SETTINGS: The setting for this small study was a regional university
      in NSW, Australia. PARTICIPANTS: Previous and completing (final year) students
      were invited to complete the online survey and any who were willing to be
      interviewed were asked to provide their contact details. METHODS: The research
      was conducted via a questionnaire through Survey Monkey, using a Likert scale and
      open responses and follow up interviews were conducted with willing participants.
      RESULTS: A total of 128 responses to the survey were received and ten were
      interviewed. Overall responses were positive. Students were aware of and valued
      all aspects of the current and proposed conceptual framework. There were some
      themes; however which were better understood than others. CONCLUSIONS: The
      majority of graduated students indicated that they were well prepared for the
      workforce. All aspects of the conceptual framework of the curriculum were valued
      by the majority of students.

PMID- 25956859
TI  - Epigenetic modifications in DNA could mimic oxidative DNA damage: A double-edged
      sword.
AB  - Methylation of cytosine at the C5 position (5mC) represents an epigenetic
      modification that plays a fundamental role in embryonic development,
      transcriptional regulation, and other processes. It can also be a mutational
      hotspot at CpG dinucleotides as a result of spontaneous hydrolytic deamination of
      5mC to thymine. The resulting G . T mismatch pair is recognized by thymine DNA
      glycosylase (TDG) and revereted to a G . C pair. Recent studies have shown that
      5mC is consecutively catalyzed into 5-hydroxymethylcytosine (5hmC), 5
      formylcytosine (5fC), and 5-carboxylcytosine (5caC) by a DNA dioxygenase from the
      ten-eleven translocation (TET) family. Two oxidative cytosine derivatives, 5fC
      and 5caC, are eliminated by TDG during active DNA demethylation. Therefore, TDG
      has versatile roles in epigenetic regulation to control the gene expression as
      well as the DNA repair pathway to prevent mutagenesis. 5fC and 5caC serve as
      intermediate products of active DNA demethylation and also behave as DNA damages
      that threaten genomic integrity. Here, we discuss the potential functions of 5mC
      oxidative derivatives in epigenetic modification and DNA damage.

PMID- 25956860
TI  - The hidden side of unstable DNA repeats: Mutagenesis at a distance.
AB  - Structure-prone DNA repeats are common components of genomic DNA in all kingdoms
      of life. In humans, these repeats are linked to genomic instabilities that result
      in various hereditary disorders, including many cancers. It has long been known
      that DNA repeats are not only highly polymorphic in length but can also cause
      chromosomal fragility and stimulate gross chromosomal rearrangements, i.e.,
      deletions, duplications, inversions, translocations and more complex shuffles.
      More recently, it has become clear that inherently unstable DNA repeats
      dramatically elevate mutation rates in surrounding DNA segments and that these
      mutations can occur up to ten kilobases away from the repetitive tract, a
      phenomenon we call repeat-induced mutagenesis (RIM). This review describes
      experimental data that led to the discovery and characterization of RIM and
      discusses the molecular mechanisms that could account for this phenomenon. 

PMID- 25956861
TI  - Multifaceted control of DNA repair pathways by the hypoxic tumor
      microenvironment.
AB  - Hypoxia, as a pervasive feature in the microenvironment of solid tumors, plays a
      significant role in cancer progression, metastasis, and ultimately clinical
      outcome. One key cellular consequence of hypoxic stress is the regulation of DNA
      repair pathways, which contributes to the genomic instability and mutator
      phenotype observed in human cancers. Tumor hypoxia can vary in severity and
      duration, ranging from acute fluctuating hypoxia arising from temporary blockages
      in the immature microvasculature, to chronic moderate hypoxia due to sparse
      vasculature, to complete anoxia at distances more than 150 MUM from the nearest
      blood vessel. Paralleling the intra-tumor heterogeneity of hypoxia, the effects
      of hypoxia on DNA repair occur through diverse mechanisms. Acutely, hypoxia
      activates DNA damage signaling pathways, primarily via post-translational
      modifications. On a longer timescale, hypoxia leads to transcriptional and/or
      translational downregulation of most DNA repair pathways including DNA double
      strand break repair, mismatch repair, and nucleotide excision repair.
      Furthermore, extended hypoxia can lead to long-term persistent silencing of
      certain DNA repair genes, including BRCA1 and MLH1, revealing a mechanism by
      which tumor suppressor genes can be inactivated. The discoveries of the hypoxic
      modulation of DNA repair pathways have highlighted many potential ways to target
      susceptibilities of hypoxic cancer cells. In this review, we will discuss the
      multifaceted hypoxic control of DNA repair at the transcriptional, post
      transcriptional, and epigenetic levels, and we will offer perspective on the
      future of its clinical implications.

PMID- 25956862
TI  - Exonuclease 1-dependent and independent mismatch repair.
AB  - DNA mismatch repair (MMR) acts to repair mispaired bases resulting from
      misincorporation errors during DNA replication and also recognizes mispaired
      bases in recombination (HR) intermediates. Exonuclease 1 (Exo1) is a 5' -> 3'
      exonuclease that participates in a number of DNA repair pathways. Exo1 was
      identified as an exonuclease that participates in Saccharomyces cerevisiae and
      human MMR where it functions to excise the daughter strand after mispair
      recognition, and additionally Exo1 functions in end resection during HR. However,
      Exo1 is not absolutely required for end resection during HR in vivo. Similarly,
      while Exo1 is required in MMR reactions that have been reconstituted in vitro,
      genetics studies have shown that it is not absolutely required for MMR in vivo
      suggesting the existence of Exo1-independent and Exo1-dependent MMR subpathways.
      Here, we review what is known about the Exo1-independent and Exo1-dependent
      subpathways, including studies of mutations in MMR genes that specifically
      disrupt either subpathway.

PMID- 25956864
TI  - Emerging role of protein phosphatases changes the landscape of phospho-signaling
      in DNA damage response.
AB  - Phosphorylation signaling networks have primarily been studied from an activation
      perspective, with protein phosphatases viewed as simple counter-balances that
      functioned passively in the wake of kinase activity. Indeed, there have been only
      sporadic efforts to investigate the independent role of phosphatases in DNA
      damage response (DDR). However, global phosphoproteomic analysis of the DDR
      revealed that over one-third of observed phosphorylation sites were down
      regulated within minutes of DNA damage, suggesting a more robust role for
      phosphatases in DNA repair. Consistent with these observations, recent studies
      reveal that dephosphorylation of DNA repair factors during specific phases of the
      cell cycle may be a pre-requisite for their participation in the DDR. Here, we
      summarize recent literature and speculate on the emerging role of phosphatases in
      the DDR. 

PMID- 25956863
TI  - Yet another job for Dna2: Checkpoint activation.
AB  - Mec1 (ATR in humans) is the principal kinase responsible for checkpoint
      activation in response to replication stress and DNA damage in Saccharomyces
      cerevisiae. Checkpoint initiation requires stimulation of Mec1 kinase activity by
      specific activators. The complexity of checkpoint initiation in yeast increases
      with the complexity of chromosomal states during the different phases of the cell
      cycle. In G1 phase, the checkpoint clamp 9-1-1 is both necessary and sufficient
      for full activation of Mec1 kinase whereas in G2/M, robust checkpoint function
      requires both 9-1-1 and the replisome assembly protein Dpb11 (human TopBP1). A
      third activator, Dna2, is employed specifically during S phase to stimulate Mec1
      kinase and to initiate the replication checkpoint. Dna2 is an essential nuclease
      helicase that is required for proper Okazaki fragment maturation, for double
      strand break repair, and for protecting stalled replication forks. Remarkably,
      all three Mec1 activators use an unstructured region of the protein, containing
      two critically important aromatic residues, in order to activate Mec1. A role for
      these checkpoint activators in channeling aberrant replication structures into
      checkpoint complexes is discussed. 

PMID- 25956865
TI  - BRCA1: Beyond double-strand break repair.
AB  - Since its discovery, the BRCA1 tumor suppressor has been shown to play a role in
      multiple DNA damage response pathways. Here, we will review the involvement of
      BRCA1 in base-excision DNA repair and highlight its clinical implications. 

PMID- 25956867
TI  - Porcine small intestinal submucosa (SIS) myringoplasty in children: A randomized
      controlled study.
AB  - INTRODUCTION: A novel bioactive material for tissue graft, derived from porcine
      small intestinal mucosa (SIS) has been marketed. This material promotes early
      vessel growth, provides scaffolding for the remodeling tissues, and is
      inexpensive and ready-to-use. We evaluated efficacy, safety, and surgery time of
      SIS myringoplasty, in comparison with autologous temporalis fascia (PTF) repair
      in children in a prospective, two-group (SIS and PTF) randomized, blinded study
      at a tertiary-care pediatric institution. MATERIALS AND METHODS: 404 children
      with tympanic membrane (TM) repair were randomly assigned to receive SIS or PTF
      myringoplasty. Primary outcome was the healing of the TM at 6 months. Secondary
      outcomes were surgical time, and adverse events. Long-term follow-up ranging from
      11 to 2 years was obtained in all enrolled children. Audiometric tests as pure
      tone thresholds were applied in all patients. The Fisher's exact test and the
      Kriskal-Wallis test were applied for statistical analysis. RESULTS AND
      DISCUSSIONS: Four-hundred-thirty-two TM perforations were treated, 217 in the SIS
      and 215 in the PTF groups. There were 209 stable TM closures in the SIS (96.3%)
      and 204 (94.8%) in the PTF arm. This difference was not statistically significant
      (odds ratio=0.4, 95%; confidence interval=0.12-1.41). SIS myringoplasty yielded
      reduced surgical time. No adverse reaction to SIS was encountered. Audiometric
      tests revealed no statistically significant difference in the two groups.
      CONCLUSIONS: SIS myringoplasty is a safe and effective method for TM closure in
      children with reduced surgical time, as compared to PTF.

PMID- 25956868
TI  - Chemopreventive efficacy of menthol on carcinogen-induced cutaneous carcinoma
      through inhibition of inflammation and oxidative stress in mice.
AB  - Inflammation and oxidative stress have been implicated in various pathological
      processes including skin tumorigenesis. Skin cancer is the most common form of
      cancer responsible for considerable morbidity and mortality, the treatment
      progress of which remains slow though. Therefore, chemoprevention and other
      strategies are being considered. Menthol has shown high anticancer activity
      against various human cancers, but its effect on skin cancer has never been
      evaluated. We herein investigated the chemopreventive potential of menthol
      against 9,10-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13
      acetate (TPA)-induced inflammation, oxidative stress and skin carcinogenesis in
      female ICR mice. Pretreatment with menthol at various doses significantly
      suppressed tumor formation and growth, and markedly reduced tumor incidence and
      volume. Moreover, menthol inhibited TPA-induced skin hyperplasia and
      inflammation, and significantly suppressed the expression of cyclooxygenase-2
      (COX-2). Furthermore, pretreatment with menthol inhibited the formation of
      reactive oxygen species and affected the activities of a battery of antioxidant
      enzymes in the skin. The expressions of NF-kappaB, Erk and p38 were down
      regulated by menthol administration. Thus, inflammation and oxidative stress
      collectively played a crucial role in the chemopreventive efficacy of menthol on
      the murine skin tumorigenesis. 

PMID- 25956866
TI  - Biochemical mechanism of DSB end resection and its regulation.
AB  - DNA double-strand breaks (DSBs) in cells can undergo nucleolytic degradation to
      generate long 3' single-stranded DNA tails. This process is termed DNA end
      resection, and its occurrence effectively commits to break repair via homologous
      recombination, which entails the acquisition of genetic information from an
      intact, homologous donor DNA sequence. Recent advances, prompted by the
      identification of the nucleases that catalyze resection, have revealed intricate
      layers of functional redundancy, interconnectedness, and regulation. Here, we
      review the current state of the field with an emphasis on the major questions
      that remain to be answered. Topics addressed will include how resection initiates
      via the introduction of an endonucleolytic incision close to the break end, the
      molecular mechanism of the conserved MRE11 complex in conjunction with Sae2/CtIP
      within such a model, the role of BRCA1 and 53BP1 in regulating resection
      initiation in mammalian cells, the influence of chromatin in the resection
      process, and potential roles of novel factors. 

PMID- 25956869
TI  - The endocannabinoid system and associative learning and memory in zebrafish.
AB  - In zebrafish the medial pallium of the dorsal telencephalon represents an
      amygdala homolog structure, which is crucially involved in emotional associative
      learning and memory. Similar to the mammalian amygdala, the medial pallium
      contains a high density of endocannabinoid receptor CB1. To elucidate the role of
      the zebrafish endocannabinoid system in associative learning, we tested the
      influence of acute and chronic administration of receptor agonists (THC,
      WIN55,212-2) and antagonists (Rimonabant, AM-281) on two different learning
      paradigms. In an appetitively motivated two-alternative choice paradigm, animals
      learned to associate a certain color with a food reward. In a second set-up, a
      fish shuttle-box, animals associated the onset of a light stimulus with the
      occurrence of a subsequent electric shock (avoidance conditioning). Once fish
      successfully had learned to solve these behavioral tasks, acute receptor
      activation or inactivation had no effect on memory retrieval, suggesting that
      established associative memories were stable and not alterable by the
      endocannabinoid system. In both learning tasks, chronic treatment with receptor
      antagonists improved acquisition learning, and additionally facilitated reversal
      learning during color discrimination. In contrast, chronic CB1 activation
      prevented aversively motivated acquisition learning, while different effects were
      found on appetitively motivated acquisition learning. While THC significantly
      improved behavioral performance, WIN55,212-2 significantly impaired color
      association. Our findings suggest that the zebrafish endocannabinoid system can
      modulate associative learning and memory. Stimulation of the CB1 receptor might
      play a more specific role in acquisition and storage of aversive learning and
      memory, while CB1 blocking induces general enhancement of cognitive functions. 

PMID- 25956871
TI  - The effects of chronic fluoxetine treatment following injury of medial frontal
      cortex in mice.
AB  - Injury of the brain is a leading cause of long-term disability. Recent evidence
      indicates that the selective serotonin reuptake inhibitor drug fluoxetine may be
      beneficial when administered following brain injury. However, its potential to
      promote recovery and the mechanisms by which it might do so require further
      characterization. In the present experiment, fluoxetine was administered to mice
      for 4 weeks following injury of medial frontal cortex (MFC). MFC injury altered
      behavior, reducing locomotion, decreasing swim speed in the Morris water task,
      and decreasing anxiety-like behavior in the elevated plus maze. Fluoxetine
      treatment did not affect these behavioral alterations, but it did increase the
      social dominance of the injured mice, as assessed by the tube test. Fluoxetine
      treatment also hastened learning of a T-maze position discrimination task,
      independently of lesion condition. Anatomically, fluoxetine failed to decrease
      lesion size, increase the survival of cells born 1-week post injury in the
      hippocampal dentate gyrus, or reverse the reduction in spine density in layer
      II/III pyramidal neurons in cingulate cortex caused by the lesions. Fluoxetine
      did, however, increase the dendritic arborization of these cells, which was
      reduced in the mice with lesions. Thus, while not all the effects of MFC injury
      were ameliorated, the behavioral outcome of mice with MFC injuries was improved,
      and one of the neuroanatomical sequelae of the lesions counteracted, by chronic
      fluoxetine, further contributing to the evidence that fluoxetine could be a
      useful treatment following brain injury. 

PMID- 25956870
TI  - Repeated social defeat stress enhances the anxiogenic effect of bright light on
      operant reward-seeking behavior in rats.
AB  - Repeated stress can trigger episodes of depression, along with symptoms of
      anhedonia and anxiety. Although often modeled separately, anxiogenic factors
      potently modulate hedonic, or appetitive, behavior. While repeated stress can
      increase anxiety and decrease appetitive behavior, it is not clear whether
      repeated stress can influence the impact of anxiogenic factors on appetitive
      behavior. This study tests whether repeated stress shifts behavior in a task that
      measures anxiogenic-appetitive balance. To test this, adult male rats were
      trained to lever press for sucrose pellet reward, and the effect of anxiogenic
      bright light on this behavior was measured. The impact of the bright light
      anxiogenic stimulus on lever pressing was compared between groups exposed to
      either daily repeated social defeat stress or control handling. We found that
      repeated stress reduced exploration in the open field and decreased social
      interaction, but had minimal effect on baseline lever pressing for reward.
      Repeated stress substantially enhanced the effect of anxiogenic bright light on
      lever pressing. This effect was greater two days after the last stress exposure,
      and began to diminish within two weeks. These data demonstrate that the
      anxiogenic and anhedonic features induced by repeated stress can be separately
      measured, and that the impact of anxiogenic stimuli can be greatly enhanced after
      repeated stress, even in the face of appetitive drive. The data also demonstrate
      that some apparent anhedonic-like effects of repeated stress can be due to
      increased sensitivity to anxiogenic stimuli, and may reflect an imbalance in an
      appetitive approach-withdrawal continuum. 

PMID- 25956872
TI  - Midfoot Charcot Neuroarthropathy in Patients With Diabetes: The Impact of Foot
      Ulceration on Self-Reported Quality of Life.
AB  - INTRODUCTION: Charcot neuroarthropathy (CN) and diabetic foot ulceration (DFU)
      are serious complications of diabetes mellitus (DM) that can result in infection,
      hospitalization, amputation, and have been shown to negatively affect quality of
      life (QOL). To the best of our knowledge, there are no studies in the literature
      that have specifically compared QOL in patients with diabetic CN without DFU to a
      group of patients with diabetic CN and concurrent DFU. The aim of this study was
      to compare self-reported assessments of QOL in patients with CN to a group of
      patients with CN and concomitant midfoot ulceration. MATERIALS AND METHODS: We
      compared a group of 35 diabetic patients with midfoot CN and no ulcer to a group
      of 22 diabetic patients with midfoot CN and concurrent DFU. Self-reported outcome
      was assessed using the Medical Outcome Study Short Form 36 (SF-36) health survey
      and Foot and Ankle Ability Measure (FAAM). RESULTS: No significant differences
      were found when comparing the 2 groups utilizing the SF-36 and FAAM with the
      exception that CN patients without foot ulcers had lower mean scores on the
      Bodily Pain Subscale. Both groups demonstrated negative impact on physical QOL
      and lower extremity function to a greater degree than mental QOL. CONCLUSION: The
      presence of ulceration does not appear to significantly impact QOL in patients
      with CN when compared to patients with CN without ulceration. LEVELS OF EVIDENCE:
      Prognostic, Level III: Case control.

PMID- 25956873
TI  - Pictorial Review and Basic Principles of Foot and Ankle Hardware Extraction.
AB  - This pictorial review presents basic principles of the types of hardware
      extraction commonly encountered in foot and ankle surgical practice. We review
      the indications, contraindications and complications of hardware removal
      including pain, intra-articular fixation, and carcinogenesis, as well as special
      considerations in pediatric patients and in the setting of infection. Figures are
      then used to describe the appropriate techniques for use of the screwdriver
      shafts, conical extraction screws, extraction bolts, hollow reamers, and other
      instruments found in most hardware extraction sets. LEVELS OF EVIDENCE:
      Therapeutic, Level V: Expert opinion.

PMID- 25956874
TI  - Claw Toe Deformity of the Foot due to Foreign Body Granuloma.
AB  - We present a case of dynamic claw deformity of the right third toe due to a
      foreign body granuloma adhering to the flexor digitorum longus (FDL) tendon at
      the level of the body of the metacarpal bone. The deformity was completely
      corrected after removal of the granuloma and lengthening of the FDL tendon. A 25
      year-old woman presented with pain and claw deformity of the right third toe,
      which corrected with ankle plantar flexion. Ultrasound and magnetic resonance
      imaging suggested the presence of foreign body granuloma of the right FDL tendon
      at the level of body of third metacarpal bone. On removal of the granuloma and Z
      plasty of the FDL tendon, there was complete correction of the claw. In the
      reported literature, claw deformity is seen with compartment syndrome or ankle
      fractures due to fixed length phenomenon or checkrein deformity of the flexor
      tendons usually at the level of medial part of the ankle. Here, we present a case
      of checkrein claw deformity of the FDL tendon due to a foreign body granuloma.
      LEVELS OF EVIDENCE: Therapeutic, Level IV: Case study.

PMID- 25956875
TI  - A Short-Term Retrospective of First Metatarsophalangeal Joint Arthrodesis Using a
      Plate With PocketLock Fixation.
AB  - BACKGROUND: Various techniques have been described for arthrodesis of the first
      metatarsophalangeal (MTP) joint. The purpose of this study was to retrospectively
      review the results of fixation for the first MTP arthrodesis of patients treated
      using dome-shaped reamers to prepare the joint surfaces and a novel MTP Plate
      with PocketLock fixation. METHODS: Between July 2012 and November 2013, 16 feet
      in 16 patients were treated with a first MTP arthrodesis with a MTP Plate with
      PocketLock fixation. The mean patient age was 58.8 years (range, 46-82 years).
      Physical and radiographic examinations were performed at follow-up visits. The
      average follow-up period was 17.3 months. The radiographs were examined for union
      (3 bridging cortices), time to union, hardware failure, or other radiographic
      complications. The charts were reviewed to assess AOFAS-MTP-IP (American
      Orthopaedic Foot & Ankle Society metatarsophalangeal-interphalangeal) scores and
      postoperative complications. RESULTS: Fusion was seen in 11 of 16 feet (68.8%)
      and partial union in 1 patient (6.3%). Five nonunions (31.2%) were noted in the
      sample group: All were symptomatic and required revision surgery. No malunions
      were identified in our sample. One hardware failure was documented in a nonunion
      patient. The mean time to osseous union was 81.7 +/- 15.9 days. The preoperative
      AOFAS MTP-IP score was 55.6 and the postoperative score was 64.7. CONCLUSION: The
      high nonunion and revision surgery rates demonstrate that this particular plate
      should be used with caution for a first MTP joint arthrodesis. LEVEL OF EVIDENCE:
      Therapeutic, Level IV: Case series.

PMID- 25956876
TI  - In Vivo Talocrural Joint Contact Mechanics With Functional Ankle Instability.
AB  - BACKGROUND: Functional ankle instability (FAI) may involve abnormal kinematics
      and contact mechanics during ankle internal rotation. Understanding of these
      abnormalities is important to prevent secondary problems in patients with FAI.
      However, there are no in vivo studies that have investigated talocrural joint
      contact mechanics during weightbearing ankle internal rotation. The objective of
      this study to determine talocrural contact mechanics during weightbearing ankle
      internal rotation in patients with FAI. METHODS: Twelve male subjects with
      unilateral FAI (age range, 18-26 years) were enrolled. Computed tomography and
      fluoroscopic imaging of both lower extremities were obtained during weightbearing
      passive ankle joint complex rotation. Three-dimensional bone models created from
      the computed tomographic images were matched to the fluoroscopic images to
      compute 6 degrees of freedom for talocrural joint kinematics. The closest contact
      area in the talocrural joint in ankle neutral rotation and maximum internal
      rotation during either dorsiflexion or plantar flexion was determined using
      geometric bone models and talocrural joint kinematics data. RESULTS: The closest
      contact area in the talus shifted anteromedially during ankle dorsiflexion
      internal rotation, whereas it shifted posteromedially during ankle plantar
      flexion-internal rotation. The closest contact area in FAI joints was
      significantly more medial than that in healthy joints during maximum ankle
      internal rotation and was associated with excessive talocrural internal rotation
      or inversion. DISCUSSION: This study demonstrated abnormal talocrural kinematics
      and contact mechanics in FAI subjects. Such abnormal kinematics may contribute to
      abnormal contact mechanics and may increase cartilage stress in FAI joints. LEVEL
      OF EVIDENCE: Therapeutic, Level IV: cross-sectional case-control study.

PMID- 25956877
TI  - Protective effect of high concentration of BN52021 on retinal contusion in cat
      eyes.
AB  - BACKGROUND: Blunt injuries/contusion on eyes might cause retina blunt trauma.
      This study is to evaluate the protective function of BN52021 against retinal
      trauma. METHODS: A total of 70 cats, 6 months old, were divided into six groups:
      Group A to E (n = 12) and normal control (N) group (n = 10). The right eyes in
      Group A to E were contused. All experiments were performed under general
      anesthetization. Retrobulbar injections of medication in right eyes were
      performed. Cats were administrated with 0.5 mL of normal saline (NS), dimethyl
      sulphoxide, 0.2 g/L BN52021, 1 g/L BN52021 and 5 g/L BN52021, respectively. Cats
      in Group N were administrated with 0.5 mL of NS. Intraocular pressure (IOP),
      flash electroretinogram (ERG), and retinal nerve fiber layer (RNFL) thickness
      were measured. Hematoxylin and eosin (HE) staining and transmission electron
      microscope (TEM) were detected. RESULTS: No significant difference was observed
      in IOP levels among groups. Comparing with cats in Group N, those in Group A to E
      showed significant lower amplitudes of rod a- and b-waves (P < 0.05). Amplitudes
      of rod a- and b-waves were increased by administration of high concentration of
      BN52021 (>= 1 g/L). Moreover, high concentration of BN52021 decreased the RNFL
      thickness increased by contusion. Axons in RNFL in Group E arranged neatly at 7
      days after modeling. CONCLUSIONS: The degenerated axons caused by contusion were
      repaired by BN52021. The administration of high concentration of (>= 1 g/L)
      BN52021 could partially repair retinal function in contused cat eyes.

PMID- 25956878
TI  - Deletion of GIRK2 Subunit of GIRK Channels Alters the 5-HT1A Receptor-Mediated
      Signaling and Results in a Depression-Resistant Behavior.
AB  - BACKGROUND: Targeting dorsal raphe 5-HT1A receptors, which are coupled to G
      protein inwardly rectifying potassium (GIRK) channels, has revealed their
      contribution not only to behavioral and functional aspects of depression but also
      to the clinical response to its treatment. Although GIRK channels containing
      GIRK2 subunits play an important role controlling excitability of several brain
      areas, their impact on the dorsal raphe activity is still unknown. Thus, the goal
      of the present study was to investigate the involvement of GIRK2 subunit
      containing GIRK channels in depression-related behaviors and physiology of
      serotonergic neurotransmission. METHODS: Behavioral, functional, including in
      vivo extracellular recordings of dorsal raphe neurons, and neurogenesis studies
      were carried out in wild-type and GIRK2 mutant mice. RESULTS: Deletion of the
      GIRK2 subunit promoted a depression-resistant phenotype and determined the
      behavioral response to the antidepressant citalopram without altering hippocampal
      neurogenesis. In dorsal raphe neurons of GIRK2 knockout mice, and also using GIRK
      channel blocker tertiapin-Q, the basal firing rate was higher than that obtained
      in wild-type animals, although no differences were observed in other firing
      parameters. 5-HT1A receptors were desensitized in GIRK2 knockout mice, as
      demonstrated by a lower sensitivity of dorsal raphe neurons to the inhibitory
      effect of the 5-HT1A receptor agonist, 8-OH-DPAT, and the antidepressant
      citalopram. CONCLUSIONS: Our results indicate that GIRK channels formed by GIRK2
      subunits determine depression-related behaviors as well as basal and 5-HT1A
      receptor-mediated dorsal raphe neuronal activity, becoming alternative
      therapeutic targets for psychiatric diseases underlying dysfunctional serotonin
      transmission.

PMID- 25956879
TI  - The ambiguous ripening nature of the fig (Ficus carica L.) fruit: a gene
      expression study of potential ripening regulators and ethylene-related genes.
AB  - The traditional definition of climacteric and non-climacteric fruits has been put
      into question. A significant example of this paradox is the climacteric fig
      fruit. Surprisingly, ripening-related ethylene production increases following pre
      or postharvest 1-methylcyclopropene (1-MCP) application in an unexpected auto
      inhibitory manner. In this study, ethylene production and the expression of
      potential ripening-regulator, ethylene-synthesis, and signal-transduction genes
      are characterized in figs ripening on the tree and following preharvest 1-MCP
      application. Fig ripening-related gene expression was similar to that in tomato
      and apple during ripening on the tree, but only in the fig inflorescence-drupelet
      section. Because the pattern in the receptacle is different for most of the
      genes, the fig drupelets developed inside the syconium are proposed to function
      as parthenocarpic true fruit, regulating ripening processes for the whole
      accessory fruit. Transcription of a potential ripening regulator, FcMADS8,
      increased during ripening on the tree and was inhibited following 1-MCP
      treatment. Expression patterns of the ethylene-synthesis genes FcACS2, FcACS4,
      and FcACO3 could be related to the auto-inhibition reaction of ethylene
      production in 1-MCP-treated fruit. Along with FcMADS8 suppression, gene
      expression analysis revealed upregulation of FcEBF1, and downregulation of FcEIL3
      and several FcERFs by 1-MCP treatment. This corresponded with the high
      storability of the treated fruit. One FcERF was overexpressed in the 1-MCP
      treated fruit, and did not share the increasing pattern of most FcERFs in the
      tree-ripened fig. This demonstrates the potential of this downstream ethylene
      signal-transduction component as an ethylene-synthesis regulator, responsible for
      the non-climacteric auto-inhibition of ethylene production in fig. 

PMID- 25956880
TI  - PacCYP707A2 negatively regulates cherry fruit ripening while PacCYP707A1 mediates
      drought tolerance.
AB  - Sweet cherry is a non-climacteric fruit and its ripening is regulated by abscisic
      acid (ABA) during fruit development. In this study, four cDNAs (PacCYP707A1-4)
      encoding 8'-hydroxylase, a key enzyme in the oxidative catabolism of ABA, were
      identified in sweet cherry fruits using tobacco rattle virus-induced gene
      silencing (VIGS) and particle bombardment approaches. Quantitative real-time PCR
      confirmed significant down-regulation of target gene transcripts in VIGS-treated
      cherry fruits. In PacCYP707A2-RNAi-treated fruits, ripening and fruit colouring
      were promoted relative to control fruits, and both ABA accumulation and PacNCED1
      transcript levels were up-regulated by 140%. Silencing of PacCYP707A2 by VIGS
      significantly altered the transcripts of both ABA-responsive and ripening-related
      genes, including the ABA metabolism-associated genes NCED and CYP707A, the
      anthocyanin synthesis genes PacCHS, PacCHI, PacF3H, PacDFR, PacANS, and PacUFGT,
      the ethylene biosynthesis gene PacACO1, and the transcription factor PacMYBA. The
      promoter of PacMYBA responded more strongly to PacCYP707A2-RNAi-treated fruits
      than to PacCYP707A1-RNAi-treated fruits. By contrast, silencing of PacCYP707A1
      stimulated a slight increase in fruit colouring and enhanced resistance to
      dehydration stress compared with control fruits. These results suggest that
      PacCYP707A2 is a key regulator of ABA catabolism that functions as a negative
      regulator of fruit ripening, while PacCYP707A1 regulates ABA content in response
      to dehydration during fruit development. 

PMID- 25956881
TI  - The floral transcriptome of ylang ylang (Cananga odorata var. fruticosa) uncovers
      biosynthetic pathways for volatile organic compounds and a multifunctional and
      novel sesquiterpene synthase.
AB  - The pleasant fragrance of ylang ylang varieties (Cananga odorata) is mainly due
      to volatile organic compounds (VOCs) produced by the flowers. Floral scents are a
      key factor in plant-insect interactions and are vital for successful pollination.
      C. odorata var. fruticosa, or dwarf ylang ylang, is a variety of ylang ylang that
      is popularly grown in Southeast Asia as a small shrub with aromatic flowers.
      Here, we describe the combined use of bioinformatics and chemical analysis to
      discover genes for the VOC biosynthesis pathways and related genes. The scented
      flowers of C. odorata var. fruticosa were analysed by gas chromatography/mass
      spectrometry and a total of 49 VOCs were identified at four different stages of
      flower development. The bulk of these VOCs were terpenes, mainly sesquiterpenes.
      To identify the various terpene synthases (TPSs) involved in the production of
      these essential oils, we performed RNA sequencing on mature flowers. From the RNA
      sequencing data, four full-length TPSs were functionally characterized. In vitro
      assays showed that two of these TPSs were mono-TPSs. CoTPS1 synthesized four
      products corresponding to beta-thujene, sabinene, beta-pinene, and alpha
      terpinene from geranyl pyrophosphate and CoTPS4 produced geraniol from geranyl
      pyrophosphate. The other two TPSs were identified as sesqui-TPSs. CoTPS3
      catalysed the conversion of farnesyl pyrophosphate to alpha-bergamotene, whereas
      CoTPS2 was found to be a multifunctional and novel TPS that could catalyse the
      synthesis of three sesquiterpenes, beta-ylangene, beta-copaene, and beta
      cubebene. Additionally, the activities of the two sesqui-TPSs were confirmed in
      planta by transient expression of these TPS genes in Nicotiana benthamiana leaves
      by Agrobacterium-mediated infiltration. 

PMID- 25956882
TI  - Multigene manipulation of photosynthetic carbon assimilation increases CO2
      fixation and biomass yield in tobacco.
AB  - Over the next 40 years it has been estimated that a 50% increase in the yield of
      grain crops such as wheat and rice will be required to meet the food and fuel
      demands of the increasing world population. Transgenic tobacco plants have been
      generated with altered combinations of sedoheptulose-1,7-bisphosphatase, fructose
      1,6-bisphosphate aldolase, and the cyanobacterial putative-inorganic carbon
      transporter B, ictB, of which have all been identified as targets to improve
      photosynthesis based on empirical studies. It is shown here that increasing the
      levels of the three proteins individually significantly increases the rate of
      photosynthetic carbon assimilation, leaf area, and biomass yield. Furthermore,
      the daily integrated measurements of photosynthesis showed that mature plants
      fixed between 12-19% more CO2 than the equivalent wild-type plants. Further
      enhancement of photosynthesis and yield was observed when sedoheptulose-1,7
      bisphosphatase, fructose-1,6-bisphosphate aldolase, and ictB were over-expressed
      together in the same plant. These results demonstrate the potential for the
      manipulation of photosynthesis, using multigene-stacking approaches, to increase
      crop yields. 

PMID- 25956883
TI  - Comparative proteomics of root plasma membrane proteins reveals the involvement
      of calcium signalling in NaCl-facilitated nitrate uptake in Salicornia europaea.
AB  - Improving crop nitrogen (N) use efficiency under salinity is essential for the
      development of sustainable agriculture in marginal lands. Salicornia europaea is
      a succulent euhalophyte that can survive under high salinity and N-deficient
      habitat conditions, implying that a special N assimilation mechanism may exist in
      this plant. In this study, phenotypic and physiological changes of S. europaea
      were investigated under different nitrate and NaCl levels. The results showed
      that NaCl had a synergetic effect with nitrate on the growth of S. europaea. In
      addition, the shoot nitrate concentration and nitrate uptake rate of S. europaea
      were increased by NaCl treatment under both low N and high N conditions,
      suggesting that nitrate uptake in S. europaea was NaCl facilitated. Comparative
      proteomic analysis of root plasma membrane (PM) proteins revealed 81 proteins,
      whose abundance changed significantly in response to NaCl and nitrate. These
      proteins are involved in metabolism, cell signalling, transport, protein folding,
      membrane trafficking, and cell structure. Among them, eight proteins were calcium
      signalling components, and the accumulation of seven of the above-mentioned
      proteins was significantly elevated by NaCl treatment. Furthermore, cytosolic
      Ca(2+) concentration ([Ca(2+)]cyt) was significantly elevated in S. europaea
      under NaCl treatment. The application of the Ca(2+) channel blocker LaCl3 not
      only caused a decrease in nitrate uptake rate, but also attenuated the promoting
      effects of NaCl on nitrate uptake rates. Based on these results, a possible
      regulatory network of NaCl-facilitated nitrate uptake in S. europaea focusing on
      the involvement of Ca(2+) signalling was proposed. 

PMID- 25956884
TI  - AINTEGUMENTA-LIKE genes have partly overlapping functions with AINTEGUMENTA but
      make distinct contributions to Arabidopsis thaliana flower development.
AB  - AINTEGUMENTA (ANT) is an important regulator of Arabidopsis flower development
      that has overlapping functions with the related AINTEGUMENTA-LIKE6 (AIL6) gene in
      floral organ initiation, identity specification, growth, and patterning. Two
      other AINTEGUMENTA-LIKE (AIL) genes, AIL5 and AIL7, are expressed in developing
      flowers in spatial domains that partly overlap with those of ANT. Here, it is
      shown that AIL5 and AIL7 also act in a partially redundant manner with ANT. The
      results demonstrate that AIL genes exhibit unequal genetic redundancy with roles
      for AIL5, AIL6, and AIL7 only revealed in the absence of ANT function. ant ail5
      and ant ail7 double mutant flowers show alterations in floral organ positioning
      and growth, sepal fusion, and reductions in petal number. In ant ail5, petals are
      often replaced by filaments or dramatically reduced in size. ant ail7 double
      mutants produce increased numbers of carpels, which have defects in valve fusion
      and a loss of apical tissues. The distinct phenotypes of ant ail5, ant ail7 and
      the previously characterized ant ail6 indicate that AIL5, AIL6, and AIL7 make
      unique contributions to flower development. These distinct roles are also
      supported by genetic analyses of ant ail triple mutants. While ant ail5 ail6
      triple mutants closely resemble ant ail6 double mutants, ant ail5 ail7 triple
      mutants exhibit more severe deviations from the wild type than either ant ail5 or
      ant ail7 double mutants. Furthermore, it is shown that AIL5, AIL6, and AIL7 act
      in a dose dependent manners in ant and other mutant backgrounds. 

PMID- 25956887
TI  - Simulating the human brain: Scientists have started various major projects to
      simulate and understand the brain, but many neuroscientists remain sceptical
      about their scope and aims.

PMID- 25956885
TI  - Comparative transcriptome profiling approach to glean virulence and
      immunomodulation-related genes of Fasciola hepatica.
AB  - BACKGROUND: Fasciola hepatica causes chronic liver disease, fasciolosis, leading
      to significant losses in the livestock economy and concerns for human health in
      many countries. The identification of F. hepatica genes involved in the
      parasite's virulence through modulation of host immune system is utmost important
      to comprehend evasion mechanisms of the parasite and develop more effective
      strategies against fasciolosis. In this study, to identify the parasite's
      putative virulence genes which are associated with host immunomodulation, we
      explored whole transcriptome of an adult F. hepatica using current transcriptome
      profiling approaches integrated with detailed in silico analyses. In brief, the
      comparison of the parasite transcripts with the specialised public databases
      containing sequence data of non-parasitic organisms (Dugesiidae species and
      Caenorhabditis elegans) or of numerous pathogens and investigation of the
      sequences in terms of nucleotide evolution (directional selection) and cytokine
      signaling relation were conducted. RESULTS: NGS of the whole transcriptome
      resulted in 19,534,766 sequence reads, yielding a total of 40,260 transcripts
      (N50 = 522 bp). A number of the parasite transcripts (n = 1,671) were predicted
      to be virulence-related on the basis of the exclusive homology with the pathogen
      associated data, positive selection or relationship with cytokine signaling. Of
      these, a group of the virulence-related genes (n = 62), not previously described,
      were found likely to be associated with immunomodulation based on in silico
      functional categorisation, showing significant sequence similarities with various
      immune receptors (i.e. MHC I class, TGF-beta receptor, toll/interleukin-1
      receptor, T-cell receptor, TNF receptor, and IL-18 receptor accessory protein),
      cytokines (i.e. TGF-beta, interleukin-4/interleukin-13 and TNF-alpha), cluster of
      differentiations (e.g. CD48 and CD147) or molecules associated with other
      immunomodulatory mechanisms (such as regulation of macrophage activation). Some
      of the genes (n = 5) appeared to be under positive selection (Ka/Ks > 1),
      imitating proteins associated with cytokine signaling (through sequence
      homologies with thrombospondin type 1, toll/interleukin-1 receptor, TGF-beta
      receptor and CD147). CONCLUSIONS: With a comparative transcriptome profiling
      approach, we have identified a number of potential immunomodulator genes of F.
      hepatica (n = 62), which are firstly described here, could be employed for the
      development of better strategies (including RNAi) in the battle against both
      zoonotically and economically important disease, fasciolosis.

PMID- 25956886
TI  - A sulfur-based transport pathway in Cu+-ATPases.
AB  - Cells regulate copper levels tightly to balance the biogenesis and integrity of
      copper centers in vital enzymes against toxic levels of copper. PIB -type Cu(+)
      ATPases play a central role in copper homeostasis by catalyzing the selective
      translocation of Cu(+) across cellular membranes. Crystal structures of a copper
      free Cu(+)-ATPase are available, but the mechanism of Cu(+) recognition, binding,
      and translocation remains elusive. Through X-ray absorption spectroscopy, ATPase
      activity assays, and charge transfer measurements on solid-supported membranes
      using wild-type and mutant forms of the Legionella pneumophila Cu(+)-ATPase
      (LpCopA), we identify a sulfur-lined metal transport pathway. Structural analysis
      indicates that Cu(+) is bound at a high-affinity transmembrane-binding site in a
      trigonal-planar coordination with the Cys residues of the conserved CPC motif of
      transmembrane segment 4 (C382 and C384) and the conserved Met residue of
      transmembrane segment 6 (M717 of the MXXXS motif). These residues are also
      essential for transport. Additionally, the studies indicate essential roles of
      other conserved intramembranous polar residues in facilitating copper binding to
      the high-affinity site and subsequent release through the exit pathway. 

PMID- 25956889
TI  - Invited review articles: do they inform or do they advertise?

PMID- 25956888
TI  - Autocrine VEGF maintains endothelial survival through regulation of metabolism
      and autophagy.
AB  - Autocrine VEGF is necessary for endothelial survival, although the cellular
      mechanisms supporting this function are unknown. Here, we show that--even after
      full differentiation and maturation--continuous expression of VEGF by endothelial
      cells is needed to sustain vascular integrity and cellular viability. Depletion
      of VEGF from the endothelium results in mitochondria fragmentation and
      suppression of glucose metabolism, leading to increased autophagy that
      contributes to cell death. Gene-expression profiling showed that endothelial VEGF
      contributes to the regulation of cell cycle and mitochondrial gene clusters, as
      well as several--but not all--targets of the transcription factor FOXO1. Indeed,
      VEGF-deficient endothelium in vitro and in vivo showed increased levels of FOXO1
      protein in the nucleus and cytoplasm. Silencing of FOXO1 in VEGF-depleted cells
      reversed expression profiles of several of the gene clusters that were de
      regulated in VEGF knockdown, and rescued both cell death and autophagy
      phenotypes. Our data suggest that endothelial VEGF maintains vascular homeostasis
      through regulation of FOXO1 levels, thereby ensuring physiological metabolism and
      endothelial cell survival.

PMID- 25956890
TI  - Course and outcome of Early Lyme borreliosis in patients with hematological
      malignancies.
AB  - Patients with erythema migrans and underlying hematological malignancy more often
      had signs of disseminated Lyme borreliosis and more frequently needed antibiotic
      retreatment than sex-, age-, and antibiotic treatment-matched immunocompetent
      persons with erythema migrans. However, the outcome was excellent in both groups.

PMID- 25956892
TI  - Reply to Solnick.

PMID- 25956893
TI  - Editorial Commentary: Failure of Adjunctive Valacyclovir to Improve Outcomes in
      Herpes Simplex Encephalitis.

PMID- 25956894
TI  - Reply to Solnick.

PMID- 25956891
TI  - Herpes Simplex Encephalitis: Lack of Clinical Benefit of Long-term Valacyclovir
      Therapy.
AB  - BACKGROUND: Despite the proven efficacy of acyclovir (ACV) therapy, herpes
      simplex encephalitis (HSE) continues to cause substantial morbidity and
      mortality. Among patients with HSE treated with ACV, the mortality rate is
      approximately 14%-19%. Among survivors, 45%-60% have neuropsychological sequelae
      at 1 year. Thus, improving therapeutic approaches to HSE remains a high priority.
      METHODS: Following completion of a standard course of intravenous ACV, 87 adult
      patients with HSE (confirmed by positive polymerase chain reaction [PCR] for
      herpes simplex virus DNA in cerebrospinal fluid) were randomized to receive
      either valacyclovir (VACV) 2 g thrice daily (n = 40) or placebo tablets (n = 47)
      for 90 days (12 tablets of study medication daily). The primary endpoint was
      survival with no or mild neuropsychological impairment at 12 months, as measured
      by the Mattis Dementia Rating Scale (MDRS). Logistic regression was utilized to
      assess factors related to the primary endpoint. RESULTS: The demographic
      characteristics of the 2 randomization groups were statistically similar with no
      significant differences in age, sex, or race. At 12 months, there was no
      significant difference in the MDRS scoring for VACV-treated vs placebo
      recipients, with 85.7% and 90.2%, respectively, of patients demonstrating no or
      mild neuropsychological impairment (P = .72). No significant study-related
      adverse events were encountered in either treatment group. CONCLUSIONS: Following
      standard treatment with intravenous ACV for PCR-confirmed HSE, an additional 3
      month course of oral VACV therapy did not provide added benefit as measured by
      neuropsychological testing 12 months later in a population of relatively high
      functioning survivors. CLINICAL TRIALS REGISTRATION: NCT00031486.

PMID- 25956895
TI  - Sporotrichosis in the Central Nervous System Caused by Sporothrix brasiliensis.

PMID- 25956896
TI  - Incidence and clinical relevance of heterotopic ossification after internal
      fixation of acetabular fractures: retrospective cohort and case control study.
AB  - OBJECTIVE: The aim of the study was to evaluate predictors and clinical relevance
      of heterotopic ossification (HO) in patients treated for acetabular fractures in
      a tertiary referral centre. PATIENTS AND METHODS: The study is a retrospective
      cohort study with a nested case-control study. All patients treated with internal
      fixation of acetabular fractures from January 2004 to October 2013. Ninety
      patients had postoperative imaging available at 6 and 12 months postoperatively
      and received no prophylaxis. Plain radiographs were used to grade HO. The Hip
      disability and Osteoarthritis Outcome Score (HOOS) was used to compare outcomes
      between patients suffering from HO with patients who did not. RESULTS: Sixteen
      patients (17.7%) suffered from HO. According to the Brooker classification, 5 had
      class I, 4 class II, 3 class III and 4 class IV HO. Traumatic brain injury (TBI)
      was the only significant risk factor for developing HO (odds ratio (OR) 8.6, 95%
      confidence interval (CI) (1.693-43.753), p = 0.014). The HO rate in patients with
      an anterior (ilioinguinal) or posterior (Kocher-Langenbeck) surgical approach was
      20% and 21% respectively, and the HO rate in patients with a combined approach
      was much lower at 11%. Neither fracture type nor gender nor age increased the
      risk of HO significantly. The outcome measured by HOOS was not significantly
      different between patients with HO and patients in the control group. Patients
      with HO Brooker class II-IV had slightly lower (effect estimate +4.25, 95% CI (
      10.2 to +12.10), p = 0.220) HOOS compared to the majority of the control group.
      CONCLUSION: A very low rate of HO was found compared to the HO rates described in
      other studies with similar patient cohorts who received prophylaxis. Based on our
      findings and the current literature, we do not recommend giving prophylaxis
      against HO to patients after internal fixation of acetabular fractures.

PMID- 25956898
TI  - Thought-Action-Fusion.

PMID- 25956897
TI  - Increased Cerebellar Functional Connectivity With the Default-Mode Network in
      Unaffected Siblings of Schizophrenia Patients at Rest.
AB  - The default-mode network (DMN) is vital in the neurobiology of schizophrenia, and
      the cerebellum participates in the high-order cognitive network such as the DMN.
      However, the specific contribution of the cerebellum to the DMN abnormalities
      remains unclear in unaffected siblings of schizophrenia patients. Forty-six
      unaffected siblings of schizophrenia patients and 46 healthy controls were
      recruited for a resting-state scan. The images were analyzed using the functional
      connectivity (FC) method. The siblings showed significantly increased FCs between
      the left Crus I and the left superior medial prefrontal cortex (MPFC), as well as
      between the lobule IX and the bilateral MPFC (orbital part) and right superior
      MPFC compared with the controls. No significantly decreased FC was observed in
      the siblings relative to the controls. The analyses were replicated in 49 first
      episode, drug-naive patients with schizophrenia, and the results showed that the
      siblings and the patients shared increased FCs between the left Crus I and the
      left superior MPFC, as well as between the lobule IX and the left MPFC (orbital
      part) compared with the controls. These findings suggest that increased
      cerebellar-DMN connectivities emerge earlier than illness onset, which highlight
      the contribution of the cerebellum to the DMN alterations in unaffected siblings.
      The shared increased cerebellar-DMN connectivities between the patients and the
      siblings may be used as candidate endophenotypes for schizophrenia. 

PMID- 25956899
TI  - Phase II Study of Afatinib as Third-Line Treatment for Patients in Korea With
      Stage IIIB/IV Non-Small Cell Lung Cancer Harboring Wild-Type EGFR.

PMID- 25956900
TI  - Real-world study of everolimus in advanced progressive neuroendocrine tumors.

PMID- 25956902
TI  - A multicentre comparative study on the efficacy of intravenous ferric
      carboxymaltose and iron sucrose for correcting preoperative anaemia in patients
      undergoing major elective surgery British Journal of Anaesthesia, 2015; 107(3):
      477-78, DOI 10.1093/bja/aer242.

PMID- 25956901
TI  - Mode of anaesthesia for preterm Caesarean delivery: secondary analysis from the
      Maternal-Fetal Medicine Units Network Caesarean Registry.
AB  - BACKGROUND: Preterm delivery is often performed by Caesarean section. We
      investigated modes of anaesthesia and risk factors for general anaesthesia among
      women undergoing preterm Caesarean delivery. METHODS: Women undergoing Caesarean
      delivery between 24(+0) and 36(+6) weeks' gestation were identified from a
      multicentre US registry. The mode of anaesthesia was classified as neuraxial
      anaesthesia (spinal, epidural, or combined spinal and epidural) or general
      anaesthesia. Logistic regression was used to identify patient characteristic,
      obstetric, and peripartum risk factors associated with general anaesthesia.
      RESULTS: Within the study cohort, 11 539 women had preterm Caesarean delivery;
      9510 (82.4%) underwent neuraxial anaesthesia and 2029 (17.6%) general
      anaesthesia. In our multivariate model, African-American race [adjusted odds
      ratio (aOR)=1.9; 95% confidence interval (CI)=1.7-2.2], Hispanic ethnicity
      (aOR=1.5; 95% CI=1.2-1.8), other race (aOR=1.4; 95% CI=1.1-1.9), and haemolysis,
      elevated liver enzymes and low platelets (HELLP) syndrome or eclampsia (aOR=2.8;
      95% CI=2.2-3.5) were independently associated with receiving general anaesthesia
      for preterm Caesarean delivery. Women with an emergency Caesarean delivery
      indication had the highest odds for general anaesthesia (aOR=3.5; 95% CI=3.1
      3.9). For every 1 week decrease in gestational age at delivery, the adjusted odds
      of general anaesthesia increased by 13%. CONCLUSIONS: In our study cohort, nearly
      one in five women received general anaesthesia for preterm Caesarean delivery.
      Although potential confounding by unmeasured factors cannot be excluded, our
      findings suggest that early gestational age at delivery, emergent Caesarean
      delivery indications, hypertensive disease, and non-Caucasian race or ethnicity
      are associated with general anaesthesia for preterm Caesarean delivery.

PMID- 25956903
TI  - Meta- analysis and meta-regression analysis of the associations between sex and
      the operative outcomes of carotid endarterectomy.
AB  - BACKGROUND: Subgroup analyses from randomized controlled trials (RCT) of carotid
      endarterectomy (CEA) for both symptomatic and asymptomatic carotid stenosis
      suggest less benefit in women compared to men, due partly to higher age
      independent peri-operative risk. However, a meta-analysis of case series and
      databases focussing on CEA-related gender differences has never been
      investigated. METHODS: A systematic review of all available publications
      (including case series, databases and RCTs) reporting data on the association
      between sex and procedural risk of stroke and/or death following CEA from 1980 to
      2015 was investigated. Pooled Peto odds ratios of the procedural risk of stroke
      and/or death were obtained by Mantel-Haenszel random-effects meta-analysis. The
      I(2) statistic was used as a measure of heterogeneity. Potential publication bias
      was assessed with the Egger test and represented graphically with Begg funnel
      plots of the natural log of the OR versus its standard error. Additional
      sensitivity analyses were undertaken to evaluate the potential effect of key
      assumptions and study-level factors on the overall results. Meta-regression
      models were formed to explore potential heterogeneity as a result of potential
      risk factors or confounders on outcomes. A tria sequential analysis (TSA) was
      performed with the aim to maintain an over- all 5% risk of type I error, being
      the standard in most meta- analyses and systematic reviews. RESULTS: 58 articles
      reported combined stroke and mortality rates within 30 days of treatment. In the
      unselected overall meta-analysis, the incidence of stroke and death in the male
      and female groups differed significantly (Peto OR, 1,162; 95% CI, 1.067-1.266; P
      = .001), revealing a worse outcome for female patients. Moderate heterogeneity
      among the studies was identified (I(2) = 36%), and the possibility of publication
      bias was low (P = .03). In sensitivity analyses the meta-analysis of case series
      with gender aspects as a secondary outcome showed a significantly increased risk
      for 30-day stroke and death in women compared to men (Peto OR, 1.390; 95% CI,
      1.148-1.684; P = .001), In contrast, meta-analysis of databases (Peto OR, 1.025;
      95% CI, 0.958-1.097; P = .474) and case series with gender related outcomes as a
      primary aim (Peto OR, 1.202; 95% CI, 0.925-1.561; P = .168) demonstrated no
      increase in operative risk of stroke and death in women compared to men.
      CONCLUSIONS: Meta-analyses of case series and databases dealing with CEA reveal
      inconsistent results regarding gender differences related to CEA-procedure and
      should not be transferred into clinical practice.

PMID- 25956905
TI  - Selective modulation of the functions of a conserved DNA motor by a histone fold
      complex.
AB  - Budding yeast Mph1 helicase and its orthologs drive multiple DNA transactions.
      Elucidating the mechanisms that regulate these motor proteins is central to
      understanding genome maintenance processes. Here, we show that the conserved
      histone fold MHF complex promotes Mph1-mediated repair of damaged replication
      forks but does not influence the outcome of DNA double-strand break repair.
      Mechanistically, scMHF relieves the inhibition imposed by the structural
      maintenance of chromosome protein Smc5 on Mph1 activities relevant to replication
      associated repair through binding to Mph1 but not DNA. Thus, scMHF is a function
      specific enhancer of Mph1 that enables flexible response to different genome
      repair situations. 

PMID- 25956906
TI  - Stability of micronutrients and phytochemicals of grapefruit jam as affected by
      the obtention process.
AB  - Fruits are widely revered for their micronutrient properties. They serve as a
      primary source of vitamins and minerals as well as of natural phytonutrients with
      antioxidant properties. Jam constitutes an interesting way to preserve fruit.
      Traditionally, this product is obtained by intense heat treatment that may cause
      irreversible loss of these bioactive compounds responsible for the health-related
      properties of fruits. In this work, different grapefruit jams obtained by
      conventional, osmotic dehydration (OD) without thermal treatment and/or microwave
      (MW) techniques were compared in terms of their vitamin, organic acid and
      phytochemical content and their stability through three months of storage. If
      compared with heating, osmotic treatments lead to a greater loss of organic acids
      and vitamin C during both processing and storage. MW treatments permit jam to be
      obtained which has a similar nutritional and functional value than that obtained
      when using a conventional heating method, but in a much shorter time. 

PMID- 25956904
TI  - LIN28 cooperates with WNT signaling to drive invasive intestinal and colorectal
      adenocarcinoma in mice and humans.
AB  - Colorectal cancer (CRC) remains a major contributor to cancer-related mortality.
      LIN28A and LIN28B are highly related RNA-binding protein paralogs that regulate
      biogenesis of let-7 microRNAs and influence development, metabolism, tissue
      regeneration, and oncogenesis. Here we demonstrate that overexpression of either
      LIN28 paralog cooperates with the Wnt pathway to promote invasive intestinal
      adenocarcinoma in murine models. When LIN28 alone is induced genetically, half of
      the resulting tumors harbor Ctnnb1 (beta-catenin) mutation. When overexpressed in
      Apc(Min/+) mice, LIN28 accelerates tumor formation and enhances proliferation and
      invasiveness. In conditional genetic models, enforced expression of a LIN28
      resistant form of the let-7 microRNA reduces LIN28-induced tumor burden, while
      silencing of LIN28 expression reduces tumor volume and increases tumor
      differentiation, indicating that LIN28 contributes to tumor maintenance. We
      detected aberrant expression of LIN28A and/or LIN28B in 38% of a large series of
      human CRC samples (n = 595), where LIN28 expression levels were associated with
      invasive tumor growth. Our late-stage CRC murine models and analysis of primary
      human tumors demonstrate prominent roles for both LIN28 paralogs in promoting CRC
      growth and progression and implicate the LIN28/let-7 pathway as a therapeutic
      target. 

PMID- 25956907
TI  - Gene expression associated with white syndromes in a reef building coral,
      Acropora hyacinthus.
AB  - BACKGROUND: Corals are capable of launching diverse immune defenses at the site
      of direct contact with pathogens, but the molecular mechanisms of this activity
      and the colony-wide effects of such stressors remain poorly understood. Here we
      compared gene expression profiles in eight healthy Acropora hyacinthus colonies
      against eight colonies exhibiting tissue loss commonly associated with white
      syndromes, all collected from a natural reef environment near Palau. Two types of
      tissues were sampled from diseased corals: visibly affected and apparently
      healthy. RESULTS: Tag-based RNA-Seq followed by weighted gene co-expression
      network analysis identified groups of co-regulated differentially expressed genes
      between all health states (disease lesion, apparently healthy tissues of diseased
      colonies, and fully healthy). Differences between healthy and diseased tissues
      indicate activation of several innate immunity and tissue repair pathways
      accompanied by reduced calcification and the switch towards metabolic reliance on
      stored lipids. Unaffected parts of diseased colonies, although displaying a trend
      towards these changes, were not significantly different from fully healthy
      samples. Still, network analysis identified a group of genes, suggestive of
      altered immunity state, that were specifically up-regulated in unaffected parts
      of diseased colonies. CONCLUSIONS: Similarity of fully healthy samples to
      apparently healthy parts of diseased colonies indicates that systemic effects of
      white syndromes on A. hyacinthus are weak, which implies that the coral colony is
      largely able to sustain its physiological performance despite disease. The genes
      specifically up-regulated in unaffected parts of diseased colonies, instead of
      being the consequence of disease, might be related to the originally higher
      susceptibility of these colonies to naturally occurring white syndromes.

PMID- 25956908
TI  - Vitamin D, carotid intima-media thickness and bone structure in patients with
      type 2 diabetes.
AB  - Despite aggressive treatment of cardiovascular disease (CVD) risk factors
      individuals with type 2 diabetes (T2D) still have increased risk of
      cardiovascular morbidity and mortality. The primary aim of this study was to
      examine the cross-sectional association between total (25-hydroxy vitamin D
      (25(OH)D)) and risk of CVD in patients with T2D. Secondary objective was to
      examine the association between 25(OH)D and bone health. A Danish cohort of
      patients with T2D participating in a randomised clinical trial were analysed. In
      total 415 patients (68% men, age 60+/-9 years (mean+/-s.d.), duration of diabetes
      12+/-6 years), including 294 patients (71%) treated with insulin. Carotid intima
      media thickness (IMT) and arterial stiffness (carotid artery distensibility
      coefficient (DC) and Young's elastic modulus (YEM)) were measured by ultrasound
      scan as indicators of CVD. Bone health was assessed by bone mineral density and
      trabecular bone score measured by dual energy X-ray absorptiometry. In this
      cohort, 214 patients (52%) were vitamin D deficient (25(OH)D <50 nmol/l). Carotid
      IMT was 0.793+/-0.137 mm, DC was 0.0030+/-0.001 mmHg, YEM was 2354+/-1038 mmHg
      and 13 (3%) of the patients were diagnosed with osteoporosis. A 25(OH)D level was
      not associated with carotid IMT or arterial stiffness (P>0.3) or bone health
      (P>0.6) after adjustment for CVD risk factors. In conclusion, 25(OH)D status was
      not associated with carotid IMT, arterial stiffness or bone health in this cohort
      of patients with T2D. To explore these associations and the association with
      other biomarkers further, multicentre studies with large numbers of patients are
      required. 

PMID- 25956909
TI  - An unusual case of respiratory arrest.

PMID- 25956910
TI  - Academic detailing of general practitioners by a respiratory physician for
      diagnosis and management of refractory breathlessness: a randomised pilot study.
AB  - BACKGROUND: Academic detailing (AD; also known as educational visiting)
      facilitates the translation of evidence into practice and has been widely adopted
      internationally to facilitate practice change. The potential of AD linked to a
      specific patient and delivered by a specialist physician to general practitioners
      has not been evaluated. This pilot study assessed the feasibility and
      acceptability of AD on the knowledge and confidence of GPs caring for people with
      advanced cancer who had breathlessness at the end of life. METHODS: In this
      randomised controlled pilot, 35 patient/GP dyads were randomised to AD or usual
      care. Key messages included: ensuring reversible causes were optimally treated;
      non-pharmacological and pharmacological treatments were considered; and oxygen
      considered for hypoxaemic patients. RESULTS: Acceptability: The majority of GPs
      randomised to AD agreed to participate, reporting benefits to practice. The
      majority of GPs in the control group requested a copy of academic detailing
      written materials at study completion. Feasibility: AD visits to GPs' offices
      could be timetabled reasonably easily, with 24 detailing visits occurring. Self
      reported knowledge and beliefs: Ninety two percent of GPs reported the topics
      covered in the AD sessions were useful, with 83% reporting an increase in
      knowledge and confidence. AD sessions resulted in 58% of GPs reporting a change
      in their approach to the management of breathlessness. By contrast, 81% of the
      usual care group reported low confidence in the management and knowledge of
      breathlessness. CONCLUSION: AD was acceptable and feasible to participating GPs.
      This pilot supports proceeding to a fully powered study.

PMID- 25956911
TI  - The Exposure Advantage: Early Exposure to a Multilingual Environment Promotes
      Effective Communication.
AB  - Early language exposure is essential to developing a formal language system, but
      may not be sufficient for communicating effectively. To understand a speaker's
      intention, one must take the speaker's perspective. Multilingual exposure may
      promote effective communication by enhancing perspective taking. We tested
      children on a task that required perspective taking to interpret a speaker's
      intended meaning. Monolingual children failed to interpret the speaker's meaning
      dramatically more often than both bilingual children and children who were
      exposed to a multilingual environment but were not bilingual themselves. Children
      who were merely exposed to a second language performed as well as bilingual
      children, despite having lower executive-function scores. Thus, the communicative
      advantages demonstrated by the bilinguals may be social in origin, and not due to
      enhanced executive control. For millennia, multilingual exposure has been the
      norm. Our study shows that such an environment may facilitate the development of
      perspective-taking tools that are critical for effective communication. 

PMID- 25956912
TI  - Competence Judgments Based on Facial Appearance Are Better Predictors of American
      Elections Than of Korean Elections.
AB  - Competence judgments based on facial appearance predict election results in
      Western countries, which indicates that these inferences contribute to decisions
      with social and political consequence. Because trait inferences are less
      pronounced in Asian cultures, such competence judgments should predict Asian
      election results less accurately than they do Western elections. In the study
      reported here, we compared Koreans' and Americans' competence judgments from face
      to-trait inferences for candidates in U.S. Senate and state gubernatorial
      elections and Korean Assembly elections. Perceived competence was a far better
      predictor of the outcomes of real elections held in the United States than of
      elections held in Korea. When deciding which of two candidates to vote for in
      hypothetical elections, however, Koreans and Americans both voted on the basis of
      perceived competence inferred from facial appearance. Combining actual and
      hypothetical election results, we conclude that for Koreans, competence judgments
      from face-to-trait inferences are critical in voting only when other information
      is unavailable. However, in the United States, such competence judgments are
      substantially important, even in the presence of other information. 

PMID- 25956913
TI  - Significance of KRAS/PAK1/Crk pathway in non-small cell lung cancer oncogenesis.
AB  - BACKGROUND: Key effector(s) of mutated KRAS in lung cancer progression and
      metastasis are unknown. Here we investigated the role of PAK1/Crk axis in
      transduction of the oncogenic KRAS signal in non-small cell lung cancer (NSCLC).
      METHODS: We used NSCLC clinical specimens to examine the correlation among KRAS
      mutations (codon 12, 13 and 61); PAK1/Crk axis activation [p-PAK1(Thr423), p
      Crk(Ser41)]; and adhesion molecules expression by immunohistochemistry. For
      assessing the role of proto-oncogene c-Crk as a KRAS effector, we inhibited KRAS
      in NSCLC cells by a combination of farnesyltransferase inhibitor (FTI) and
      geranylgeranyltransferase inhibitor (GGTI) and measured p-Crk-II(Ser41) by
      western blotting. Finally, we disrupted the signaling network downstream of KRAS
      by blocking KRAS/PAK1/Crk axis with PAK1 inhibitors (i.e., IPA-3, FRAX597 or
      FRAX1036) along with partial inhibition of all other KRAS effectors by
      prenylation inhibitors (FTI + GGTI) and examined the motility, morphology and
      proliferation of the NSCLC cells. RESULTS: Immunohistochemical analysis
      demonstrated an inverse correlation between PAK1/Crk phosphorylation and E
      cadherin/p120-catenin expression. Furthermore, KRAS mutant tumors expressed
      higher p-PAK1(Thr423) compared to KRAS wild type. KRAS prenylation inhibition by
      (FTI + GGTI) completely dephosphorylated proto-oncogene c-Crk on Serine 41 while
      Crk phosphorylation did not change by individual prenylation inhibitors or
      diluent. Combination of PAK1 inhibition and partial inhibition of all other KRAS
      effectors by (FTI + GGTI) dramatically altered morphology, motility and
      proliferation of H157 and A549 cells. CONCLUSIONS: Our data provide evidence that
      proto-oncogene c-Crk is operative downstream of KRAS in NSCLC. Previously we
      demonstrated that Crk receives oncogenic signals from PAK1. These data in
      conjunction with the work of others that have specified the role of PAK1 in
      transduction of KRAS signal bring forward the importance of KRAS/PAK1/Crk axis as
      a prominent pathway in the oncogenesis of KRAS mutant lung cancer.

PMID- 25956914
TI  - Pharmacogenetics and the print media: what is the public told?
AB  - BACKGROUND: Pharmacogenetics is a rapidly growing field that aims to identify the
      genes that influence drug response. This science can be used as a powerful tool
      to tailor drug treatment to the genetic makeup of individuals. The present study
      explores the coverage of the topic of pharmacogenetics and its potential benefit
      in personalised medicine by the UK newsprint media. METHODS: The LexisNexis
      database was used to identify and retrieve full text articles from the 10 highest
      circulation national daily newspapers and their Sunday equivalents in the UK.
      Content analysis of newspaper articles which referenced pharmacogenetic testing
      was carried out. A second researcher coded a random sample (21%) of newspaper
      articles to establish the inter-rater reliability of coding. RESULTS: Of the 256
      articles captured by the search terms, 96 articles (with pharmacogenetics as a
      major component) met the study inclusion criteria. The majority of articles over
      stated the benefits of pharmacogenetic testing while paying less attention to the
      associated risks. Overall beneficial effects were mentioned 5.3 times more
      frequently than risks (p < 0.001). The most common illnesses for which
      pharmacogenetically based personalised medicine was discussed were cancer,
      cardiovascular disease and CNS diseases. Only 13% of newspaper articles that
      cited a specific scientific study mentioned this link in the article. There was a
      positive correlation between the size of the article and both the number of
      benefits and risks stated (P < 0.01). CONCLUSION: More comprehensive coverage of
      the area of personalised medicine within the print media is needed to inform
      public debate on the inclusion of pharmacogentic testing in routine practice.

PMID- 25956915
TI  - The prevalence of clinically diagnosed ankylosing spondylitis and its clinical
      manifestations: a nationwide register study.
AB  - INTRODUCTION: Prevalence estimates of ankylosing spondylitis vary considerably,
      and there are few nationwide estimates. The present study aimed to describe the
      national prevalence of clinically diagnosed ankylosing spondylitis in Sweden,
      stratified according to age, sex, geographical, and socio-economic factors, and
      according to subgroups with ankylosing spondylitis-related clinical
      manifestations and pharmacological treatment. METHODS: All individuals diagnosed
      with ankylosing spondylitis according to the World Health Organization
      International Classification of Disease codes, between 1967 and 2009, were
      identified from the National Patient Register. Data regarding disease
      manifestations, patient demographics, level of education, pharmacological
      treatment, and geographical region were retrieved from the National Patient
      Register and other national registers. RESULTS: A total of 11,030 cases with an
      ankylosing spondylitis diagnosis (alive, living in Sweden, and 16 to 64 years old
      in December 2009) were identified in the National Patient Register, giving a
      point prevalence of 0.18% in 2009. The prevalence was higher in northern Sweden,
      and lower in those with a higher level of education. Men had a higher prevalence
      of ankylosing spondylitis (0.23% versus 0.14%, P < 0.001), a higher frequency of
      anterior uveitis (25.5% versus 20.0%, P < 0.001) and were more likely to receive
      tumor necrosis factor inhibitors than women (15.6% versus 11.8% in 2009, P <
      0.001). Women were more likely than men to have peripheral arthritis (21.7%
      versus 15.3%, P < 0.001), psoriasis (8.0% versus 6.9%, P = 0.03), and treatment
      with oral corticosteroids (14.0% versus 10.4% in 2009, P < 0.001). CONCLUSION:
      This nationwide, register-based study demonstrated a prevalence of clinically
      diagnosed ankylosing spondylitis of 0.18%. It revealed phenotypical and treatment
      differences between the sexes, as well as geographical and socio-economic
      differences in disease prevalence.

PMID- 25956917
TI  - Empirical population and public health ethics: A review and critical analysis to
      advance robust empirical-normative inquiry.
AB  - The field of population and public health ethics (PPHE) has yet to fully embrace
      the generation of evidence as an important project. This article reviews the
      philosophical debates related to the 'empirical turn' in clinical bioethics, and
      critically analyses how PPHE has and can engage with the philosophical
      implications of generating empirical data within the task of normative inquiry. A
      set of five conceptual and theoretical issues pertaining to population health
      that are unresolved and could potentially benefit from empirical PPHE approaches
      to normative inquiry are discussed. Each issue differs from traditional empirical
      bioethical approaches, in that they emphasize (1) concerns related to the
      population, (2) 'upstream' policy-relevant health interventions - within and
      outside of the health care system and (3) the prevention of illness and disease.
      Within each theoretical issue, a conceptual example from population and public
      health approaches to HIV prevention and health promotion is interrogated. Based
      on the review and critical analysis, this article concludes that empirical
      normative approaches to population and public health ethics would be most
      usefully pursued as an iterative project (rather than as a linear project), in
      which the normative informs the empirical questions to be asked and new empirical
      evidence constantly directs conceptualizations of what constitutes morally robust
      public health practices. Finally, a conceptualization of an empirical population
      and public health ethics is advanced in order to open up new interdisciplinary
      'spaces', in which empirical and normative approaches to ethical inquiry are
      transparently (and ethically) integrated.

PMID- 25956916
TI  - Estrogen receptor beta impacts hormone-induced alternative mRNA splicing in
      breast cancer cells.
AB  - BACKGROUND: Estrogens play an important role in breast cancer (BC) development
      and progression; when the two isoforms of the estrogen receptor (ERalpha and
      ERbeta) are co-expressed each of them mediate specific effects of these hormones
      in BC cells. ERbeta has been suggested to exert an antagonist role toward the
      oncogenic activities of ERalpha, and for this reason it is considered an
      oncosuppressor. As clinical evidence regarding a prognostic role for this
      receptor subtype in hormone-responsive BC is still limited and conflicting, more
      knowledge is required on the biological functions of ERbeta in cancer cells. We
      have previously described the ERbeta and ERalpha interactomes from BC cells,
      identifying specific and distinct patterns of protein interactions for the two
      receptors. In particular, we identified factors involved in mRNA splicing and
      maturation as important components of both ERalpha and ERbeta pathways. Guided by
      these findings, here we performed RNA sequencing to investigate in depth the
      differences in the early transcriptional events and RNA splicing patterns induced
      by estradiol in cells expressing ERalpha alone or ERalpha and ERbeta. RESULTS:
      Exon skipping was the most abundant splicing event in the post-transcriptional
      regulation by estradiol. We identified several splicing events induced by ERalpha
      alone and by ERalpha+ERbeta, demonstrating for the first time that ERbeta
      significantly affects estrogen-induced splicing in BC cells, as revealed by
      modification of a subset of ERalpha-dependent splicing by ERbeta, as well as by
      the presence of splicing isoforms only in ERbeta+cells. In particular, we
      observed that ERbeta+BC cell lines exhibited around 2-fold more splicing events
      than the ERbeta- cells. Interestingly, we identified putative direct targets of
      ERbeta-mediated alternative splicing by correlating the genomic locations of
      ERbeta and ERalpha binding sites with estradiol-induced differential splicing in
      the corresponding genes. CONCLUSIONS: Taken together, these results demonstrate
      that ERbeta significantly affects estrogen-induced early transcription and mRNA
      splicing in hormone-responsive BC cells, providing novel information on the
      biological role of ERbeta in these tumors.

PMID- 25956918
TI  - Effectiveness of combination therapy with nifedipine GITS: a prospective, 12-week
      observational study (AdADOSE).
AB  - BACKGROUND: Observational studies can provide important information on the
      efficacy and safety of antihypertensive agents in the real-life clinical setting.
      AdADOSE was a large observational study to assess the effectiveness of nifedipine
      GITS in combination with other antihypertensive agent(s). The study was also the
      first to examine the role of combination therapy with nifedipine GITS in the
      Middle East, Pakistan and Russia, regions that are associated with particularly
      high cardiovascular risk. METHODS: AdADOSE was a 12-week, international,
      multicenter, prospective, observational study. Patients with hypertension (ie,
      blood pressure [BP] >140/90 mm Hg, or >130/80 mm Hg in patients at high or very
      high cardiovascular risk) received once-daily nifedipine GITS (30, 60 or 90 mg)
      in combination with another antihypertensive or as add-on to existing therapy.
      The primary study endpoint was the proportion of patients who achieved the target
      BP of <140/90 mm Hg (or <130/80 mm Hg for those at high or very high
      cardiovascular risk). Study outcomes are reported by descriptive statistics.
      RESULTS: The study enrolled 4497 patients (n = 4477, safety population; n = 3430,
      efficacy population). Baseline mean systolic/diastolic BP (SBP/DBP) was
      166.4/99.7 mm Hg; 85.2 % of patients had received prior antihypertensive
      treatment, and 90.6 % had >= 1 concomitant diseases. Following combination
      treatment with nifedipine GITS, target BP was achieved by 64.8% of patients
      without concomitant diseases, and by 56.5%, 32.3% and 22.6% with 1, 2-3 and >3
      concomitant diseases, respectively. The proportion of patients achieving target
      BP was 51.5% in previously untreated and 33.7% in previously treated patients.
      Nifedipine GITS combination treatment provided mean SBP/DBP changes of -36.1/
      18.8 mm Hg in all patients, -40.2/-21.5 mm Hg in previously untreated patients,
      and -35.6/-18.4 mm Hg in previously treated patients, with similar BP reductions
      irrespective of the number of concomitant diseases. Drug-related adverse events
      (AEs) were reported in 2.6% patients. There were no serious AEs and only 0.8% of
      patients discontinued due to drug-related AEs. CONCLUSIONS: Combination therapy
      with nifedipine GITS in a real-life observational setting was highly effective in
      reducing SBP/DBP in a range of hypertensive patients, with low rates of treatment
      related AEs. TRIAL REGISTRATION:  TRIAL REGISTRATION: at ClinicalTrials.gov
      registration number NCT01118286 .

PMID- 25956920
TI  - The need for a personalized approach for prostate cancer management.
AB  - The stratification of patients for treatment of prostate cancer is based on very
      general parameters like prostate-specific antigen, Gleason score, and TNM
      classification. We use these rough parameters for selection of active
      surveillance, active treatment, and even for the treatment selection in
      metastasized or castration-resistant prostate cancers. Up to now, we have not
      used individualized genetic classifiers for detailed sub-stratification, thus
      treating all patients as equal, and being only moderately successful. With the
      expected increase in systemic treatments, there is an apparent need for such
      classifiers. We will address these needs in this short commentary. 

PMID- 25956919
TI  - Biochemical and Kinetic Characterization of the Eukaryotic Phosphotransacetylase
      Class IIa Enzyme from Phytophthora ramorum.
AB  - Phosphotransacetylase (Pta), a key enzyme in bacterial metabolism, catalyzes the
      reversible transfer of an acetyl group from acetyl phosphate to coenzyme A (CoA)
      to produce acetyl-CoA and Pi. Two classes of Pta have been identified based on
      the absence (Pta(I)) or presence (Pta(II)) of an N-terminal regulatory domain.
      Pta(I) has been fairly well studied in bacteria and one genus of archaea;
      however, only the Escherichia coli and Salmonella enterica Pta(II) enzymes have
      been biochemically characterized, and they are allosterically regulated. Here, we
      describe the first biochemical and kinetic characterization of a eukaryotic Pta
      from the oomycete Phytophthora ramorum. The two Ptas from P. ramorum, designated
      PrPta(II)1 and PrPta(II)2, both belong to class II. PrPta(II)1 displayed positive
      cooperativity for both acetyl phosphate and CoA and is allosterically regulated.
      We compared the effects of different metabolites on PrPta(II)1 and the S.
      enterica Pta(II) and found that, although the N-terminal regulatory domains share
      only 19% identity, both enzymes are inhibited by ATP, NADP, NADH,
      phosphoenolpyruvate (PEP), and pyruvate in the acetyl-CoA/Pi-forming direction
      but are differentially regulated by AMP. Phylogenetic analysis of bacterial,
      archaeal, and eukaryotic sequences identified four subtypes of Pta(II) based on
      the presence or absence of the P-loop and DRTGG subdomains within the N-terminal
      regulatory domain. Although the E. coli, S. enterica, and P. ramorum enzymes all
      belong to the IIa subclass, our kinetic analysis has indicated that enzymes
      within a subclass can still display differences in their allosteric regulation. 

PMID- 25956921
TI  - Synergism Between Anticholinergic and Oxime Treatments Against Sarin-Induced
      Ocular Insult in Rats.
AB  - Eye exposure to the extremely toxic organophosphorus sarin results in long-term
      miosis and visual impairment. As current treatment using atropine or homatropine
      eye drops may lead to considerable visual side effects, alternative combined
      treatments of intramuscular (im) oximes (16.8 umol/kg, im) with atropine (0.5
      mg/kg, im) or with the short acting antimuscarinic tropicamide (0.5%; w/v) eye
      drops were thus evaluated. The combined treatments efficacy following topical
      exposure to sarin (1 ug) was assessed by measuring pupil width and light reflex
      using an infra-red based digital photographic system. Results showed that the
      combined treatment of various oximes with atropine or with topical tropicamide
      eye drops rapidly reversed the sarin-induced miosis and presented a long-term
      improvement of 67-98% (oxime+tropicamide) or 84-109% (oxime+atropine) in pupil
      widening as early as 10-min following treatment. This recovery was shown to
      persist for at least 8-h following exposure. All combined treatments facilitated
      the ability of the iris to contract following sarin insult as tested by a light
      reflex response.Our findings emphasize the high efficacy of im oxime treatment
      combined with either atropine im or tropicamide eye drops in counteracting sarin
      induced ocular insult. Therefore, in a mass casualty scenario the systemic
      combined treatment may be sufficient to ameliorate sarin-induced ocular insult
      with no need for additional, topical anticholinergic treatment at least in the
      initial stage of intoxication. For very mild casualties, who are unlikely to
      receive im treatment, the combined oxime (im) with topical tropicamide treatment
      may be sufficient in ameliorating the ocular insult. 

PMID- 25956922
TI  - Dynamic phenotypes of degenerative myxomatous mitral valve disease: quantitative
      3-dimensional echocardiographic study.
AB  - BACKGROUND: Fibro-elastic deficiency (FED) and diffuse myxomatous degeneration
      (DMD) are phenotypes of degenerative mitral valve disease defined
      morphologically. Whether physiological differences in annular and valvular
      dynamics exist between these phenotypes remains unknown. METHODS AND RESULTS: We
      performed triple quantitation of cardiac remodeling and of mitral regurgitation
      severity and of annular and valvular dimensions by real-time 3-dimensional
      transesophageal-echocardiography. Forty-nine patients with degenerative mitral
      valve disease classified as FED (n=31) and DMD (n=18) by surgical observation
      showed no difference in age (65+/-10 versus 59+/-13; P=0.5), body surface area
      (2.0+/-0.2 versus 2.0+/-0.2 m(2); P=0.5), left ventricular and atrial dimensions
      (all P>0.55), and mitral regurgitation regurgitant orifice (P=0.62). On average,
      annular dimensions were larger in DMD versus FED, but height was similar
      resulting in lower saddle shape. Dynamically, annular DMD versus FED display
      poorer contraction and saddle-shape accentuation in early systole and abnormal
      enlargement, particularly intercommissural, in late-systole (all P<0.05).
      Valvular dynamics showed stable valvular area in systole in FED versus
      considerable systolic increased area in DMD (P<0.001). Prolapse height and volume
      increased little throughout systole in FED versus marked increase in DMD
      (P<0.001). CONCLUSIONS: Our novel observations show that FED and DMD, although
      both labeled myxomatous, display considerable physiological phenotypic
      differences. In DMD, the annular increased size and profoundly abnormal dynamics
      demonstrate DMD-specific annular degeneration compared with the enlarged but
      relatively normal FED annulus. DMD does not incur more severe mitral
      regurgitation, despite larger prolapse and valve redundancy, underscoring
      potential compensatory role of tissue redundancy of DMD (or aggravating role of
      tissue paucity of FED) on mitral regurgitation severity.

PMID- 25956923
TI  - Dynamic changes of the mitral valve annulus: new look at mitral valve diseases.

PMID- 25956924
TI  - Utility of a novel inflammatory marker, GlycA, for assessment of rheumatoid
      arthritis disease activity and coronary atherosclerosis.
AB  - INTRODUCTION: GlycA is a novel inflammatory biomarker measured using nuclear
      magnetic resonance (NMR). Its NMR signal primarily represents glycosylated acute
      phase proteins. GlycA was associated with inflammation and development of
      cardiovascular disease in initially healthy women. We hypothesized that GlycA is
      a biomarker of disease activity and is associated with coronary artery
      atherosclerosis in patients with rheumatoid arthritis (RA). METHODS: We conducted
      a cross-sectional study of 166 patients with RA and 90 control subjects. GlycA
      was measured from an NMR signal originating from N-acetylglucosamine residues on
      circulating glycoproteins. The relationship between GlycA and RA disease activity
      (Disease Activity Score based on 28 joints (DAS28)) and coronary artery calcium
      score was determined. RESULTS: GlycA concentrations were higher in patients with
      RA (median (interquartile range): 398 MUmol/L (348 to 473 MUmol/L)) than control
      subjects (344 MUmol/L (314 to 403 MUmol/L) (P < 0.001). In RA, GlycA was strongly
      correlated with DAS28 based on erythrocyte sedimentation rate (DAS28-ESR) and
      DAS28 based on C-reactive protein (DAS28-CRP) and their components, including
      tender and swollen joint counts, global health score, ESR and CRP (all P <
      0.001). The area under the receiver operating characteristic curve for GlycA's
      ability to differentiate between patients with low versus moderate to high
      disease activity based on DAS28-CRP was 0.75 (95% confidence interval (CI): 0.68,
      0.83). For each quartile increase in GlycA, the odds of having coronary artery
      calcium increased by 48% (95% CI: 4%, 111%), independent of age, race and sex (P
      = 0.03). CONCLUSION: GlycA is a novel inflammatory marker that may be useful for
      assessment of disease activity and is associated with coronary artery
      atherosclerosis in patients with RA.

PMID- 25956925
TI  - The metaphyseal bone defect in distal radius fractures and its implication on
      trabecular remodeling-a histomorphometric study (case series).
AB  - BACKGROUND: The invention of the locking plate technology leads to alterations of
      treatment strategies at metaphyseal fracture sites with the concept of
      spontaneous remodeling of trabecular bone voids. Whereas trabecular regeneration
      has been proven in experimental animal studies, no histologic data exist on human
      fracture healing with special emphasis on bone voids. METHODS: In order to
      qualify the trabecular bone remodeling capacity in vivo, bone specimens from the
      metaphyseal bone void were analyzed 14 months after trauma using quantitative
      histomorphometry. Twenty-five patients with an unstable dorsally displaced distal
      radius fracture were fixed with a palmar locking plate without additional bone
      graft or substitute. At implant removal, specimens from the previous compression
      void were harvested with a trephine in a volar-dorsal direction. In 16 patients,
      histomorphometric analysis could be performed, comparing the dorsal trabecular
      network with the volar, non-compressed ultrastructure. RESULTS: Significant
      differences for bone volume/total volume (BV/TV), trabecular number (TbN) and
      trabecular separation (TbSp), but not for trabecular thickness (TbTh) and osteoid
      volume/total volume (OV/TV), were detected. Neither patient age, defect size nor
      gender had a significant influence on bone remodeling. CONCLUSIONS: The results
      of this study indicate that trabecular bone remodeling does not lead to pre
      trauma bone quality in metaphyseal bone compression voids following reduction and
      application of a locking plate.

PMID- 25956926
TI  - What is the effect of a combined physical activity and fall prevention
      intervention enhanced with health coaching and pedometers on older adults'
      physical activity levels and mobility-related goals? Study protocol for a
      randomised controlled trial.
AB  - BACKGROUND: Physical inactivity and falls in older people are important public
      health problems. Health conditions that could be ameliorated with physical
      activity are particularly common in older people. One in three people aged 65
      years and over fall at least once annually, often resulting in significant
      injuries and ongoing disability. These problems need to be urgently addressed as
      the population proportion of older people is rapidly rising. This trial aims to
      establish the impact of a combined physical activity and fall prevention
      intervention compared to an advice brochure on objectively measured physical
      activity participation and mobility-related goal attainment among people aged
      60+. METHODS/DESIGN: A randomised controlled trial involving 130 consenting
      community-dwelling older people will be conducted. Participants will be
      individually randomised to a control group (n = 65) and receive a fall prevention
      brochure, or to an intervention group (n = 65) and receive the brochure plus
      physical activity promotion and fall prevention intervention enhanced with health
      coaching and a pedometer. Primary outcomes will be objectively measured physical
      activity and mobility-related goal attainment, measured at both six and 12 months
      post randomisation. Secondary outcomes will include: falls, the proportion of
      people meeting the physical activity guidelines, quality of life, fear of
      falling, mood, and mobility limitation. Barriers and enablers to physical
      activity participation will be measured 6 months after randomisation. General
      linear models will be used to assess the effect of group allocation on the
      continuously-scored primary and secondary outcome measures, after adjusting for
      baseline scores. Between-group differences in goal attainment (primary outcome)
      will be analysed with ordinal regression. The number of falls per person-year
      will be analysed using negative binomial regression models to estimate the
      between-group difference in fall rates after one year (secondary outcome).
      Modified Poisson regression models will compare groups on dichotomous outcome
      measures. Analyses will be pre-planned, conducted while masked to group
      allocation and will use an intention-to-treat approach. DISCUSSION: This trial
      will address a key gap in evidence regarding physical activity and fall
      prevention for older people and will evaluate a program that could be directly
      implemented within Australian health services. TRIAL REGISTRATION:
      ACTRN12614000016639, 7/01/2014.

PMID- 25956927
TI  - In Vivo Mechanical Characterization of the Distraction Callus During Bone
      Consolidation.
AB  - Understanding the evolution of callus mechanical properties over time provides
      insights in the mechanobiology of fracture healing and tissue differentiation,
      can be used to validate numerical models, and informs clinical practice. Bone
      transport experiments were performed in sheep, in which a distractor type
      Ilizarov was implanted. The forces through the fixator evolution were measured
      and the callus stiffness was estimated from these forces. Computerized tomography
      images were taken and bone volume of the callus at different stages was obtained.
      The results showed that the maximum bone tissue production rate (0.146 cm3/day)
      was achieved 20 days after the end of the distraction phase. 50 days after the
      end of the distraction phase, the callus was ossified completely and had its
      maximum volume, 6-10 cm3 In addition, 80-90% of the load sustained by the
      operated limb was recovered and the callus stiffness increased exponentially
      until 5.4-11.4 kN/mm, still below 10% of the healthy level of callus stiffness.
      The effects of the bony bridging of the callus and the time of the fixator
      removal on callus force, stiffness and volume were analyzed. These outcomes
      allowed relating quantifiable biological aspects (callus volume and tissue
      production rate) with mechanical parameters (callus force and stiffness) using
      data from the same experiment.

PMID- 25956929
TI  - Maximizing antimalarial efficacy and the importance of dosing strategies.
AB  - Artemisinin-based combination therapies (ACTs) are the cornerstone for the
      treatment of malaria. However, confirmed resistance to artemisinins in South-East
      Asia, and reports of reduced efficacy of ACTs raise major concerns for malaria
      treatment and control. Without new drugs to replace artemisinins, it is essential
      to define dosing strategies that maximize therapeutic efficacy, limit the spread
      of resistance, and preserve the clinical value of ACTs. It is important to
      determine the extent to which reduced efficacy of ACTs reflects true resistance
      versus sub-optimal dosing, and quantify other factors that determine treatment
      failure. Pooled analyses of individual patient data from multiple clinical
      trials, by investigators in the Worldwide Antimalarial Resistance Network, have
      shown high overall efficacy for three widely used ACTs, artemether-lumefantrine,
      artesunate-amodiaquine, and dihydroartemisinin-piperaquine. Analyses also
      highlight that suboptimal dosing leads to increased risk of treatment failure,
      especially among children. In the most recent study, an analysis of clinical
      trials of artesunate-amodiaquine, widely used among children in Africa, revealed
      a superior efficacy for fixed-dose combination tablets compared to loose non
      fixed dose combinations. This highlights the benefits of fixed-dose combinations
      as a practical strategy for ensuring optimal antimalarial dosing and maximizing
      efficacy. Please see related article: http://www.biomedcentral.com/1741
      7015/13/66.

PMID- 25956930
TI  - Characterization of extended-spectrum beta-lactamases and antimicrobial
      resistance of Klebsiella pneumoniae in intra-abdominal infection isolates in
      Latin America, 2008-2012. Results of the Study for Monitoring Antimicrobial
      Resistance Trends.
AB  - The Study for Monitoring Antimicrobial Resistance Trends has monitored the in
      vitro activity of several recommended antimicrobials used in the management of
      intra-abdominal infections (IAIs) globally since 2002. In this report, we
      document the changing susceptibility patterns to recommended antimicrobials in
      Klebsiella pneumoniae isolates from patients with IAIs in 11 Latin American
      countries between 2008 and 2012 and describe the beta-lactamases encoded by
      phenotypically extended-spectrum beta-lactamase (ESBL)-positive and ertapenem
      nonsusceptible isolates. Overall, the incidence of phenotypically ESBL-positive
      K. pneumoniae did not change significantly from 2008 (40.4%) to 2012 (41.2%) (P >
      0.05). However, trend analysis documented an increase in isolates encoding K.
      pneumoniae carbapenemase (KPC) or both KPC and an ESBL. Decreasing susceptibility
      (P < 0.05) was noted for cefepime, ceftazidime, ceftriaxone, ertapenem, and
      imipenem among all K. pneumoniae, as well as for cefepime, cefotaxime, cefoxitin,
      ceftriaxone, ertapenem, and imipenem among ESBL-positive isolates, while
      susceptibility of ESBL-negative isolates to ampicillin-sulbactam actually
      increased (P < 0.05).

PMID- 25956928
TI  - Enhanced expression of ROCK in left atrial myocytes of mitral regurgitation: a
      potential mechanism of myolysis.
AB  - BACKGROUND: Severe mitral regurgitation (MR) may cause myolysis in the left
      atrial myocytes. Myolysis may contribute to atrial enlargement. However, the
      relationship between Rho-associated kinase (ROCK) and myolysis in the left atrial
      myocytes of MR patients remain unclear. METHODS: This study comprised 22 patients
      with severe MR [12 with atrial fibrillation (AF) and ten in sinus rhythm]. Left
      atrial appendage tissues were obtained during surgery. Normal left atrial tissues
      were purchased. Immunofluorescence histochemical and immunoblotting studies were
      performed. RESULTS: The expression of ROCK2 in the myolytic left atrial myocytes
      of MR AF patients (p = 0.009) and MR sinus patients (p = 0.011) were
      significantly higher than that of the normal subjects. Similarly, the expression
      of ROCK1 in the myolytic left atrial myocytes of MR AF patients was significantly
      higher than that of the normal subjects (p = 0.010), and the expression of ROCK1
      in the myolytic left atrial myocytes of MR sinus patients was higher than that of
      the normal subjects (p = 0.091). Immunofluorescence study revealed significant co
      localization and juxtaposition of ROCK2 and cleaved caspase-3 in the left atrial
      myocytes both in the MR AF group (Pearson's coefficient = 0.74 +/- 0.03) and the
      MR sinus group (Pearson's coefficient = 0.73 +/- 0.02). Similarly,
      immunofluorescence study revealed significant co-localization and juxtaposition
      of ROCK1 and cleaved caspase-3 in the left atrial myocytes both in the MR AF
      group (Pearson's coefficient = 0.65 +/- 0.03) and the MR sinus group (Pearson's
      coefficient = 0.65 +/- 0.03). Correlation analysis demonstrated that there was a
      significant direct relationship between the expression of ROCK2 in the myolytic
      left atrial myocytes and left atrial diameter in the MR patients (p = 0.041; r =
      0.440). Moreover, the ratio of phosphorylated myosin-binding subunit of myosin
      light chain phosphatase (pMBS)/total MBS of left atrial tissues was significantly
      higher in the MR AF group (p < 0.04) and the MR sinus group (p < 0.04) compared
      with the normal control group. CONCLUSIONS: The enhanced expression of ROCKs
      might be involved in the myolysis of the left atrial myocytes of MR patients.

PMID- 25956931
TI  - Small hospitals matter: insights from the emergence and spread of vancomycin
      resistant enterococci in 2 public hospitals in inner Brazil.
AB  - Although vancomycin-resistant enterococci (VRE) are reported in Brazil since
      1996, data on their impact over settings of different complexity are scarce. We
      performed a study aimed at identifying determinants of VRE emergence and spread
      in a public hospital consortium (comprising 2 hospitals, with 318 and 57 beds) in
      inner Brazil. Molecular typing and case-control studies (addressing predictors of
      acquisition or clonality) were performed. Among 122 authocthonous isolates, 106
      were Enterococcus faecium (22 clones), and 16, Enterococcus faecalis (5 clones).
      Incidence was greater in the small-sized hospital, and a previous admission to
      this hospital was associated with greater risk of VRE colonization or infection
      during admission to the larger one. Overall risk factors included comorbidities,
      procedures, and antimicrobials (piperacillin-tazobactam, cefepime, and imipenem).
      Risk factors varied among different hospitals, species, and clones. Our findings
      demonstrate that VRE can spread within low-complexity facilities and from these
      to larger hospitals. 

PMID- 25956933
TI  - A new angiographic imaging platform reduces radiation exposure for patients with
      liver cancer treated with transarterial chemoembolization.
AB  - OBJECTIVES: To quantify the reduction of radiation liver cancer patients are
      exposed to during transarterial chemoembolization (TACE), while maintaining
      diagnostic image quality, using a new C-arm imaging platform. METHODS: In this
      prospective, HIPAA-compliant, IRB-approved, two-arm trial, 78 consecutive
      patients with primary or secondary liver cancer were treated with TACE on a C-arm
      imaging platform before and after an upgrade incorporating optimized acquisition
      parameters and advanced real-time image processing algorithms. Dose area product
      (DAP) and radiation time of each digital fluoroscopy (DF), digital subtraction
      angiography (DSA) and cone beam CT (CBCT) were recorded. DSA image quality was
      assessed by two blinded and independent readers on a four-rank scale. RESULTS:
      Both cohorts showed no significant differences with regard to patient
      characteristics and tumour burden. The new system resulted in a statistically
      significant reduction of cumulative DAP of 66% compared to the old platform
      (median 132.9 vs. 395.8 Gy cm(2)). Individually, DAP of DF, DSA and CBCT
      decreased by 52%, 79% and 15% (p < 0.01, p < 0.01, p = 0.51), respectively. No
      statistically significant differences in DSA image quality were found between the
      two imaging platforms. CONCLUSIONS: The new imaging platform significantly
      reduced radiation exposure for TACE procedures without increased radiation time
      or negative impact on DSA image quality. KEY POINTS: * The new C-arm system
      allowed reduction of radiation exposure by two thirds * The procedure's course
      was not affected by the new platform * No decrease in DSA image quality was
      observed after the radiation reduction.

PMID- 25956932
TI  - Lipid metabolism and Type VII secretion systems dominate the genome scale
      virulence profile of Mycobacterium tuberculosis in human dendritic cells.
AB  - BACKGROUND: Mycobacterium tuberculosis continues to kill more people than any
      other bacterium. Although its archetypal host cell is the macrophage, it also
      enters, and survives within, dendritic cells (DCs). By modulating the behaviour
      of the DC, M. tuberculosis is able to manipulate the host's immune response and
      establish an infection. To identify the M. tuberculosis genes required for
      survival within DCs we infected primary human DCs with an M. tuberculosis
      transposon library and identified mutations with a reduced ability to survive.
      RESULTS: Parallel sequencing of the transposon inserts of the surviving mutants
      identified a large number of genes as being required for optimal intracellular
      fitness in DCs. Loci whose mutation attenuated intracellular survival included
      those involved in synthesising cell wall lipids, not only the well-established
      virulence factors, pDIM and cord factor, but also sulfolipids and PGL, which have
      not previously been identified as having a direct virulence role in cells. Other
      attenuated loci included the secretion systems ESX-1, ESX-2 and ESX-4, alongside
      many PPE genes, implicating a role for ESX-5. In contrast the canonical ESAT-6
      family of ESX substrates did not have intra-DC fitness costs suggesting an
      alternative ESX-1 associated virulence mechanism. With the aid of a gene-nutrient
      interaction model, metabolic processes such as cholesterol side chain catabolism,
      nitrate reductase and cysteine-methionine metabolism were also identified as
      important for survival in DCs. CONCLUSION: We conclude that many of the virulence
      factors required for survival in DC are shared with macrophages, but that
      survival in DCs also requires several additional functions, such as cysteine
      methionine metabolism, PGLs, sulfolipids, ESX systems and PPE genes.

PMID- 25956934
TI  - Improved visualization of breast cancer features in multifocal carcinoma using
      phase-contrast and dark-field mammography: an ex vivo study.
AB  - OBJECTIVES: Conventional X-ray attenuation-based contrast is inherently low for
      the soft-tissue components of the female breast. To overcome this limitation, we
      investigate the diagnostic merits arising from dark-field mammography by means of
      certain tumour structures enclosed within freshly dissected mastectomy samples.
      METHODS: We performed grating-based absorption, absolute phase and dark-field
      mammography of three freshly dissected mastectomy samples containing bi- and
      multifocal carcinoma using a compact, laboratory Talbot-Lau interferometer.
      Preoperative in vivo imaging (digital mammography, ultrasound, MRI),
      postoperative histopathological analysis and ex vivo digital mammograms of all
      samples were acquired for the diagnostic verification of our results. RESULTS: In
      the diagnosis of multifocal tumour growth, dark-field mammography seems superior
      to standard breast imaging modalities, providing a better resolution of small,
      calcified tumour nodules, demarcation of tumour boundaries with desmoplastic
      stromal response and spiculated soft-tissue strands extending from an invasive
      ductal breast cancer. CONCLUSIONS: On the basis of selected cases, we demonstrate
      that dark-field mammography is capable of outperforming conventional mammographic
      imaging of tumour features in both calcified and non-calcified tumours. Presuming
      dose optimization, our results encourage further studies on larger patient
      cohorts to identify those patients that will benefit the most from this promising
      additional imaging modality. KEY POINTS: * X-ray dark-field mammography provides
      significantly improved visualization of tumour features * X-ray dark-field
      mammography is capable of outperforming conventional mammographic imaging * X-ray
      dark-field mammography provides imaging sensitivity towards highly dispersed
      calcium grains.

PMID- 25956935
TI  - Scaled signal intensity of uterine fibroids based on T2-weighted MR images: a
      potential objective method to determine the suitability for magnetic resonance
      guided focused ultrasound surgery of uterine fibroids.
AB  - OBJECTIVES: Magnetic Resonance-guided Focused Ultrasound Surgery (MRgFUS) is a
      non-invasive method to treat uterine fibroids. To help determine the patient
      suitability for MRgFUS, we propose a new objective measure: the scaled signal
      intensity (SSI) of uterine fibroids in T2 weighted MR images (T2WI). METHODS:
      Forty three uterine fibroids in 40 premenopausal women were included in this
      retrospective study. SSI of each fibroid was measured from the screening T2WI by
      standardizing its mean signal intensity to a 0-100 scale, using reference
      intensities of rectus abdominis muscle (0) and subcutaneous fat (100).
      Correlation between the SSI and the non-perfused volume (NPV) ratio (a measure
      for treatment success) was calculated. RESULTS: Pre-treatment SSI showed a
      significant inverse-correlation with post treatment NPV ratio (p < 0.05). When
      dichotomizing NPV ratio at 45 %, the optimal cut off value of the SSI was found
      to be 16.0. CONCLUSIONS: A fibroid with SSI value 16.0 or less can be expected to
      have optimal responses. The SSI of uterine fibroids in T2WI can be suggested as
      an objective parameter to help in patient selection for MRgFUS. KEY POINTS: *
      Signal intensity of fibroid in MR images predicts treatment response to MRgFUS. *
      Signal intensity is standardized into scaled form using adjacent tissues as
      references. * Fibroids with SSI less than 16.0 are expected to have optimal
      responses.

PMID- 25956936
TI  - CT Radiogenomic Characterization of EGFR, K-RAS, and ALK Mutations in Non-Small
      Cell Lung Cancer.
AB  - OBJECTIVES: To assess the association between CT features and EGFR, ALK, KRAS
      mutations in non-small cell lung cancer. METHODS: Patients undergoing chest CT
      and testing for the above gene mutations were included. Qualitative evaluation of
      CTs included: lobe; lesion diameter; shape; margins; ground-glass opacity;
      density; cavitation; air bronchogram; pleural thickening; intratumoral necrosis;
      nodules in tumour lobe; nodules in non-tumour lobes; pleural retraction;
      location; calcifications; emphysema; fibrosis; pleural contact; pleural effusion.
      Statistical analysis was performed to assess association of features with each
      gene mutation. ROC curves for gene mutations were drawn; the corresponding area
      under the curve was calculated. P-values <0.05 were considered significant.
      RESULTS: Of 285 patients, 60/280 (21.43 %) were positive for EGFR mutation;
      31/270 (11.48 %) for ALK rearrangement; 64/240 (26.67 %) for KRAS mutation. EGFR
      mutation was associated with air bronchogram, pleural retraction, females, non
      smokers, small lesion size, and absence of fibrosis. ALK rearrangements were
      associated with age and pleural effusion. KRAS mutation was associated with round
      shape, nodules in non-tumour lobes, and smoking. CONCLUSIONS: This study
      disclosed associations between CT features and alterations of EGFR (air
      bronchogram, pleural retraction, small lesion size, absence of fibrosis), ALK
      (pleural effusion) and KRAS (round lesion shape, nodules in non-tumour lobes).
      KEY POINTS: Air bronchogram, pleural retraction, small size relate to EGFR
      mutation in NSCLC. Pleural effusion and younger age relate to ALK mutation. Round
      lesion shape, nodules in non-tumour lobes relate to KRAS mutation.

PMID- 25956937
TI  - Ultrasound-guided core-needle biopsy in thyroid nodules. A study of 676
      consecutive cases with surgical correlation.
AB  - OBJECTIVES: To analyze the diagnostic accuracy of ultrasound-guided core-needle
      biopsy (CNB) of thyroid nodules. METHODS: Of 3517 CNBs performed using an 18G
      spring-loaded device in one institution, we retrospectively reviewed 676 nodules
      in 629 consecutive patients who underwent surgery. CNB and pathological
      examination were compared. CNB diagnosis was standardized in four categories:
      insufficient (I), benign (B), follicular lesion (FOL), and malignant (M). Main
      outcome measures were predictive positive values (PPV), false positives (FP), and
      false negatives (FN). RESULTS: CNB showed a low rate of insufficient and FOL
      diagnoses (5.8 % and 4.5 %). On surgery, there were eight FNs in 374 benign CNBs
      and three FPs in 148 malignant CNBs. The 154 nodules classified as FOL in CNB
      included, at surgery, 122 neoplasms; 28 of them malignant. PPV for malignancy of
      a malignant CNB was 98 %, and for a CNB diagnosis of FOL 18.2 %. Sensitivity for
      malignancy if CNB of FOL and M are considered positive was 95.6. Only one major
      complication was observed. CONCLUSIONS: CNB is reliable, safe, and accurate to
      evaluate thyroid nodules and can be an alternative technique to FNA. It has low
      rate of non-diagnostic and undetermined cases, with high sensitivity and PPV. KEY
      POINTS: Thyroid core-needle biopsy (CNB) has high sensitivity and PPV. Pitfalls
      of CNB are rare. Pitfalls are due to cystic cancer, histological heterogeneity,
      and mistakes in analysis. CNB is a reliable, safe, and accurate method to
      approach thyroid nodules. CNB can be used primarily or after insufficient or
      indeterminate FNA.

PMID- 25956938
TI  - Visual assessment of early emphysema and interstitial abnormalities on CT is
      useful in lung cancer risk analysis.
AB  - OBJECTIVES: Screening for lung cancer should be limited to a high-risk
      population, and abnormalities in low-dose computed tomography (CT) screening
      images may be relevant for predicting the risk of lung cancer. Our aims were to
      compare the occurrence of visually detected emphysema and interstitial
      abnormalities in subjects with and without lung cancer in a screening population
      of smokers. METHODS: Low-dose chest CT examinations (baseline and latest
      possible) of 1990 participants from The Danish Lung Cancer Screening Trial were
      independently evaluated by two observers who scored emphysema and interstitial
      abnormalities. Emphysema (lung density) was also measured quantitatively.
      RESULTS: Emphysema was seen more frequently and its extent was greater among
      participants with lung cancer on baseline (odds ratio (OR), 1.8, p = 0.017 and p
      = 0.002) and late examinations (OR 2.6, p < 0.001 and p < 0.001). No significant
      difference was found using quantitative measurements. Interstitial abnormalities
      were more common findings among participants with lung cancer (OR 5.1, p < 0.001
      and OR 4.5, p < 0.001).There was no association between presence of emphysema and
      presence of interstitial abnormalities (OR 0.75, p = 0.499). CONCLUSIONS: Even
      early signs of emphysema and interstitial abnormalities are associated with lung
      cancer. Quantitative measurements of emphysema-regardless of type-do not show the
      same association. KEY POINTS: * Visually detected emphysema on CT is more
      frequent in individuals who develop lung cancer. * Emphysema grading is higher in
      those who develop lung cancer. * Interstitial abnormalities, including discrete
      changes, are associated with lung cancer. * Quantitative lung density
      measurements are not useful in lung cancer risk prediction. * Early CT signs of
      emphysema and interstitial abnormalities can predict future risk.

PMID- 25956939
TI  - Abundance and Diversity of CO2-Assimilating Bacteria and Algae Within Red
      Agricultural Soils Are Modulated by Changing Management Practice.
AB  - Elucidating the biodiversity of CO(2)-assimilating bacterial and algal
      communities in soils is important for obtaining a mechanistic view of terrestrial
      carbon sinks operating at global scales. "Red" acidic soils (Orthic Acrisols)
      cover large geographic areas and are subject to a range of management practices,
      which may alter the balance between carbon dioxide production and assimilation
      through changes in microbial CO(2)-assimilating populations. Here, we determined
      the abundance and diversity of CO(2)-assimilating bacteria and algae in acidic
      soils using quantitative PCR and terminal restriction fragment length
      polymorphism (T-RFLP) of the cbbL gene, which encodes the key CO(2) assimilation
      enzyme (ribulose-1,5-bisphosphate carboxylase/oxygenase) in the Calvin cycle.
      Within the framework of a long-term experiment (Taoyuan Agro-ecosystem,
      subtropical China), paddy rice fields were converted in 1995 to four alternative
      land management regimes: natural forest (NF), paddy rice (PR), maize crops (CL),
      and tea plantations (TP). In 2012 (17 years after land use transformation), we
      collected and analyzed the soils from fields under the original and converted
      land management regimes. Our results indicated that fields under the PR soil
      management system harbored the greatest abundance of cbbL copies (4.33 * 10(8)
      copies g(-1) soil). More than a decade after converting PR soils to natural,
      rotation, and perennial management systems, a decline in both the diversity and
      abundance of cbbL-harboring bacteria and algae was recorded. The lowest abundance
      of bacteria (0.98 * 10(8) copies g(-1) soil) and algae (0.23 * 10(6) copies g(-1)
      soil) was observed for TP soils. When converting PR soil management to
      alternative management systems (i.e., NF, CL, and TP), soil edaphic factors (soil
      organic carbon and total nitrogen content) were the major determinants of
      bacterial autotrophic cbbL gene diversity. In contrast, soil phosphorus
      concentration was the major regulator of algal cbbL community composition. Our
      results provide new insights into the diversity, abundance, and modulation of
      organisms responsible for microbial autotrophic CO(2) fixation in red acidic
      soils subjected to changing management regimes.

PMID- 25956940
TI  - Molecular Mechanisms of Enhanced Bacterial Growth on Hexadecane with Red Clay.
AB  - Red clay was previously used to enhance bioremediation of diesel-contaminated
      soil. It was speculated that the enhanced degradation of diesel was due to
      increased bacterial growth. In this study, we selected Acinetobacter oleivorans
      DR1, a soil-borne degrader of diesel and alkanes, as a model bacterium and
      performed transcriptional analysis using RNA sequencing to investigate the
      cellular response during hexadecane utilization and the mechanism by which red
      clay promotes hexadecane degradation. We confirmed that red clay promotes the
      growth of A. oleivorans DR1 on hexadecane, a major component of diesel, as a sole
      carbon source. Addition of red clay to hexadecane-utilizing DR1 cells highly
      upregulated beta-oxidation, while genes related to alkane oxidation were highly
      expressed with and without red clay. Red clay also upregulated genes related to
      oxidative stress defense, such as superoxide dismutase, catalase, and
      glutaredoxin genes, suggesting that red clay supports the response of DR1 cells
      to oxidative stress generated during hexadecane utilization. Increased membrane
      fluidity in the presence of red clay was confirmed by fatty acid methyl ester
      analysis at different growth phases, suggesting that enhanced growth on
      hexadecane could be due to increased uptake of hexadecane coupled with
      upregulation of downstream metabolism and oxidative stress defense. The
      monitoring of the bacterial community in soil with red clay for a year revealed
      that red clay stabilized the community structure. 

PMID- 25956941
TI  - Trafficking of the signature protein of intra-erythrocytic Plasmodium berghei
      induced structures, IBIS1, to P. falciparum Maurer's clefts.
AB  - Remodeling of the host red blood cell by Plasmodium falciparum is well
      established and crucial for infection and parasite virulence. Host cell
      modifications are not exclusive to human Plasmodium parasites and also occur in
      hepatocytes and erythrocytes infected with murine Plasmodium parasites. The
      recently described intra-erythrocytic P. berghei-induced structures (IBIS) share
      similarities to P. falciparum Maurer's clefts. It is shown here that a potential
      candidate IBIS1 homologue in P. falciparum, PfHYP12 (PF3D7_1301400), is partially
      exported into the erythrocyte cytoplasm. To analyze a potential similarity
      between IBIS and Maurer's clefts we expressed the signature protein of IBIS in P.
      falciparum parasites. Visualization of the tagged protein revealed that PbIBIS1
      can be exported by P. falciparum and localizes to Maurer's clefts in P.
      falciparum-infected erythrocytes, which indicates that IBIS and Maurer's clefts
      may be evolutionarily conserved parasite-induced structures in infected
      erythrocytes. 

PMID- 25956942
TI  - Pulmonary manifestation of a condition resembling Kasabach-Merritt syndrome in a
      woman with abdominal angiomatosis associated with consumptive coagulopathy-
      surgical management: a case report.
AB  - INTRODUCTION: Kasabach-Merritt syndrome is a benign condition characterized by
      hemangiomatosis, severely disseminated intravascular consumption coagulopathy,
      and thrombocytopenia. The mortality rate increases from 12% to 30% in hemorrhagic
      cases. In general, the symptoms primarily manifest in the gastrointestinal tract,
      the skin, and the subcutaneous tissue. There is no publication about pulmonary
      manifestation of angiomatosis in combination with vascular malformation and
      hemoptysis. This is the first description of a Kasabach-Merritt syndrome-like
      condition in the lung. CASE PRESENTATION: We present the case of a 29-year-old
      German woman with angiomatosis and associated pulmonary vascular malformation in
      her lower left lobe with a Kasabach-Merritt syndrome like condition. It was
      detected after hemoptysis. We also present our case observations and management.
      CONCLUSION: In a case of angiomatosis with an associated pulmonary lobar vascular
      malformation, lobectomy can be safely performed to prevent life-threatening
      bleeding.

PMID- 25956944
TI  - Potential of the chemical dinotefuran in the control of Rhipicephalus sanguineus
      (Latreille, 1806) (Acari: Ixodidae) semi-engorged female ticks.
AB  - Ticks are vectors of several pathogens to vertebrates, including the human being.
      They produce lesions on the hosts during the blood feeding and great economic
      losses. Several chemical acaricides have been used in an attempt to control tick
      infestations; however these substances are harmful to both the human being and
      non-target organisms, and to the environment. Therefore, there is a need to fight
      these ectoparasites through less harmful methods, less aggressive to the
      environment, non-target organisms and to the human health. The present study
      examined the efficacy of dinotefuran on the susceptibility of Rhipicephalus
      sanguineus semi-engorged females exposed to different concentrations of the
      product. Its lethal concentration of 50% (LC50) at 95% confidence interval was
      determined. The ticks were immersed in Petri dishes containing different
      concentrations of dinotefuran or distilled water for 5 minutes and then dried and
      maintained in an incubator for 7 days. The results showed the daily number of
      dead R. sanguineus semi-engorged females after being treated with different
      concentrations of dinotefuran. The mortality data in bioassay 2 were subjected to
      Probit analysis, where a LC50 of 10,182.253 ppm (8725.987-13,440.084) and 95%
      confidence interval were estimated. The susceptibility of R. sanguineus semi
      engorged females to dinotefuran in higher concentrations of the acaricide was
      demonstrated, indicating that its effect is probably dose-dependent. In addition,
      the action of dinotefuran was slow and gradual, interfering in the development
      and growth of the individuals throughout the observation period (7 days).

PMID- 25956943
TI  - Real-Time Evolution of a Subtelomeric Gene Family in Candida albicans.
AB  - Subtelomeric regions of the genome are notable for high rates of sequence
      evolution and rapid gene turnover. Evidence of subtelomeric evolution has relied
      heavily on comparisons of historical evolutionary patterns to infer trends and
      frequencies of these events. Here, we describe evolution of the subtelomeric TLO
      gene family in Candida albicans during laboratory passaging for over 4000
      generations. C. albicans is a commensal and opportunistic pathogen of humans and
      the TLO gene family encodes a subunit of the Mediator complex that regulates
      transcription and affects a range of virulence factors. We identified 16 distinct
      subtelomeric recombination events that altered the TLO repertoire. Ectopic
      recombination between subtelomeres on different chromosome ends occurred
      approximately once per 5000 generations and was often followed by loss of
      heterozygosity, resulting in the complete loss of one TLO gene sequence with
      expansion of another. In one case, recombination within TLO genes produced a
      novel TLO gene sequence. TLO copy number changes were biased, with some TLOs
      preferentially being copied to novel chromosome arms and other TLO genes being
      frequently lost. The majority of these nonreciprocal recombination events
      occurred either within the 3' end of the TLO coding sequence or within a
      conserved 50-bp sequence element centromere-proximal to TLO coding sequence.
      Thus, subtelomeric recombination is a rapid mechanism of generating genotypic
      diversity through alterations in the number and sequence of related gene family
      members.

PMID- 25956945
TI  - Effects of 5,8-dimethylthieno[2,3-b]quinoline-2-carboxylic acid on the
      antioxidative defense and lipid membranes in Plasmodium berghei-infected
      erythrocytes.
AB  - Plasmodium parasites degrade hemoglobin producing reactive oxygen species as
      toxic byproducts which are detoxified by a series of antioxidant mechanisms.
      Quinoline compounds have demonstrated activity against hemoglobin degradation
      with 5,8-dimethylthieno[2,3-b]quinoline-2-carboxylic acid (TQCA) representing a
      recent compound inhibiting this process. Thus, this study was undertaken to
      determine the ability of TQCA to modify the oxidative status in Plasmodium
      berghei-infected erythrocytes. After hemolysis, activities of superoxide
      dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione
      reductase (GR) and dehydrogenase enzymes as well as lipid peroxidation were
      investigated by spectrophotometry. Saturated and unsaturated fatty acids were
      determined by gas-liquid chromatography and the in vivo effects of TQCA were
      confirmed by a malaria murine model (Rane test). The activity of glucose-6
      phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH) in
      infected cells was diminished by this compound compared to control infection in
      75.1 +/- 3.5% and 26.5 +/- 0.3%, respectively, while that of GPx and GR was also
      lowered (p <0.05). As an adaptive response we appreciated a 2.3-fold increase of
      SOD activity compared to control infection. Lipid peroxidation and the
      saturated/unsaturated fatty acids ratio were also decreased by this quinoline
      derivate in 49.2 +/- 1.32% and 37 +/- 0.06%, respectively, protecting the cells
      from hemolysis caused by the infection. The in vitro results were in concordance
      with the potential in vivo activity of this compound in an established malaria
      murine model in which TQCA showed significant decrease in the parasitemia levels
      and increased the mean survival days of infected mice. In conclusion, the
      antioxidant defense represents a biochemical target for TQCA actions as a potent
      antimalarial whose effects were also confirmed in vivo.

PMID- 25956946
TI  - Evaluation of immune protective efficacies of Eimeria tenella EtMic1 polypeptides
      with different domain recombination displayed on yeast surface.
AB  - In the present study, three different live oral vaccines using the EBY100/pCTCON
      2 yeast surface display system with different Eimeria tenella microneme-1
      (EtMic1) protein domain recombination were constructed and their protective
      efficacies against homologous challenge were compared by evaluating the body
      weight gains, relative growth rate, cecal lesion scores, oocyst output, oocyst
      decrease ratio, anti-coccidial index, the serum antibody levels and the
      proliferation ability of blood lymphocytes. The results indicated that all the
      three constructed live oral vaccines expressing different EtMic1 polypeptides
      provided excellent protection against homologous challenge by significantly
      increasing weight gains, reducing cecal lesions, achieving a high ACI, elevating
      specific antibody response and splenocyte proliferation ability compared with
      controls. The yeasts displaying the EtMic1 polypeptide-III (expressed TSP-2, TSP
      3 and TSP-4 domains) provided better protection against challenge than the yeasts
      displaying either the EtMic1 polypeptide-I (expressed I-domain, TSP-1 and TSP-2)
      or polypeptide-II (expressed I-domain and all the five TSP domains) did.
      Considering the exclusion of antibiotic resistant gene in the system, the strain
      EBY100 of Saccharomyces cerevisiae may be a better choice for coccidian antigen
      delivery.

PMID- 25956947
TI  - Development of a new oxygen consumption rate assay in cultures of Acanthamoeba
      (Protozoa: Lobosea) and its application to evaluate viability and amoebicidal
      activity in vitro.
AB  - A new fluorometric method has been developed for measuring the oxygen consumption
      rate (OCR) of Acanthamoeba cultures in microplates and for screening molecules
      with amoebicidal activity against this microorganism. The use of a biofunctional
      matrix (containing an oxygen-sensitive fluorogenic probe) attached to the
      microplate wells allowed continuous measurement of OCR in the medium, hence
      assessment of amoebic growth. The new OCR method applied to cell viability
      yielded a linear relationship and monitoring was much quicker than with indirect
      viability assays previously used. In addition, two drugs were tested in a
      cytotoxicity assay monitored by the new OCR viability test. With this procedure,
      the standard amoebicidal drug chlorhexidine digluconate showed an IC50 of 3.53 +
      1.3 mg/l against Acanthamoeba polyphaga and 3.19 + 1.2 mg/l against Acanthamoeba
      castellanii, whereas a cationic dendrimer [G1Si(NMe3+)4] showed an IC50 of 6.42 +
      1.3 mg/l against A. polyphaga. These data agree with previous studies conducted
      in our laboratory. Therefore, the new OCR method has proven powerful and quick
      for amoebicidal drug screening and is likely to be applied in biochemical studies
      concerning protozoa respiration and metabolism.

PMID- 25956948
TI  - Babesia divergens apical membrane antigen-1 (BdAMA-1): A poorly polymorphic
      protein that induces a weak and late immune response.
AB  - Babesiosis is an important veterinary and zoonotic tick borne disease caused by
      the hemoprotozoan Babesia spp. which infects red blood cell of its vertebrate
      host. In order to control the infection, vaccination that targets molecules
      involved in the invasion process of red blood cells could provide a good
      alternative to chemotherapy. Among these molecules, Apical Membrane Antigen-1
      (AMA-1) has been described as an excellent vaccine candidate in Plasmodium spp.
      In this paper, we have investigated AMA-1 of Babesia divergens (BdAMA-1) as
      vaccine candidate by evaluating its polymorphism and by studying the humoral
      response against BdAMA-1 of sheep experimentally infected with B. divergens.
      Polymorphism of BdAMA-1 was investigated by sequencing the corresponding gene of
      9 B. divergens isolates from different geographical areas in France. Two Bdama-1
      haplotypes (A and B) could be defined based on 2 non-synonymous point mutations.
      In silico prediction of linear epitopes revealed that the antigenicity of the 2
      haplotypes is very similar. Antibody production against the extracellular domain
      of BdAMA-1 is weak and late, between 1 and 5 months after the inoculation of
      parasites. Both IgG1 and IgG2 are components of the anti-BdAMA-1 response. These
      results indicate that while BdAMA-1 may not be an immuno-dominant antigen, it
      could induce a mixed type 1 and type 2 immune response. In light of these
      results, the potential of BdAMA-1 as vaccine candidate is discussed.

PMID- 25956949
TI  - Online-haemodiafiltration vs. conventional haemodialysis: a cross-over study.
AB  - BACKGROUND: The main short-term advantages of haemodiafiltration (HDF) are
      supposedly better removal of Beta2-microglobulin (beta2-m) and phosphate, and
      better haemodynamic stability. The main disadvantage is higher costs. The aim of
      the study was to compare the clinical and biological parameters associated with
      HDF and high-flux haemodialysis (HD), using a cross-over design, while
      maintaining the same dialysis parameters. METHODS: All patients on a 3 * 4 hours
      schedule were observed during 3 identical 6-months periods: HDF1 - HD - HDF2. The
      mean values for the 2 last months of each period were compared. RESULTS: A total
      of 51 patients (76 % males, 45 % diabetic) with a mean age of 74 +/- 15 years,
      and who had been on dialysis for 49 +/- 60 months were included. The mean blood
      flow (329 +/- 27 ml/min), dialysate flow (500 ml/min), and convection volumes
      (21.6 +/- 3.2 L) were recorded. Patient medications were not changed. Predialysis
      blood pressure, phosphataemia, calcaemia, iPTH, Kt/V, nPNA and intradialytic
      events were similar throughout the 3 periods. Only serum albumin (34. 4 +/- 3.6,
      35.9 +/- 3.4, 34.1 +/- 4 g/L, p < 0. 0001) and beta2-m serum levels (26.1 +/-
      5.4, 28 +/- 6, 26.5 +/- 5 mg/L, p < 0.001, values shown for HDF1, HD, HDF2,
      respectively) were significantly lower during the HDF periods. Factor associated
      with higher delta serum albumin levels between HD and HDF periods was mainly a
      lower convection volume. CONCLUSION: Comparing HDF and HD, we did not observe any
      differences in haemodynamic stability or in serum phosphate levels. Only serum
      beta2-m (-6% vs. HD) and albumin (-5% vs. HD) levels changed. The long-term
      clinical consequences of these biochemical differences should be prospectively
      assessed.

PMID- 25956950
TI  - A Gonadotropin-Releasing Hormone (GnRH) Stimulation Test Before and After GnRH
      Analogue Treatment for Central Precocious Puberty: Has the GnRH Test been
      Adequately Simplified?
AB  - OBJECTIVE: To investigate and simplify the gonadotropin-releasing hormone (GnRH)
      stimulation test for assessing pubertal activation and suppression. METHODS: The
      authors identified 72 girls diagnosed with central precocious puberty who were
      treated with a GnRH analogue (GnRHa). Patients who underwent an assessment
      regarding GnRHa-mediated puberty suppression had been diagnosed via the GnRH
      stimulation test prior to GnRHa treatment. The authors analyzed the diagnostic
      values of the during/before-treatment LH levels at different time points by a
      receiver-operating characteristic (ROC) curve. RESULTS: Before GnRHa treatment,
      the mean luteinizing hormone (LH) level was higher at the 30-min test time point
      than at baseline or the 15, 60, 90, and 120-min points (P < 0.001). After GnRHa
      treatment, the LH levels were suppressed in 62 patients (86.1%) and inadequately
      suppressed in 10 (13.9%). The LH level was higher at the 30-min test time point
      than those at baseline or the 45 and 60-min level (P < 0.001). The area under the
      curve in a post-GnRHa treatment was greatest at 30 min. CONCLUSIONS: The
      simplified GnRH test is adequate for evaluating pubertal activation (30 and/or 45
      min time points of the GnRH test) and suppression (the 30-min time point).

PMID- 25956951
TI  - Form Follows Function: A Model for Clinical Supervision of Genetic Counseling
      Students.
AB  - Supervision plays a vital role in genetic counselor training, yet models
      describing genetic counseling supervision processes and outcomes are lacking.
      This paper describes a proposed supervision model intended to provide a framework
      to promote comprehensive and consistent clinical supervision training for genetic
      counseling students. Based on the principle "form follows function," the model
      reflects and reinforces McCarthy Veach et al.'s empirically derived model of
      genetic counseling practice - the "Reciprocal Engagement Model" (REM). The REM
      consists of mutually interactive educational, relational, and psychosocial
      components. The Reciprocal Engagement Model of Supervision (REM-S) has similar
      components and corresponding tenets, goals, and outcomes. The 5 REM-S tenets are:
      Learning and applying genetic information are key; Relationship is integral to
      genetic counseling supervision; Student autonomy must be supported; Students are
      capable; and Student emotions matter. The REM-S outcomes are: Student understands
      and applies information to independently provide effective services, develop
      professionally, and engage in self-reflective practice. The 16 REM-S goals are
      informed by the REM of genetic counseling practice and supported by prior
      literature. A review of models in medicine and psychology confirms the REM-S
      contains supervision elements common in healthcare fields, while remaining unique
      to genetic counseling. The REM-S shows promise for enhancing genetic counselor
      supervision training and practice and for promoting research on clinical
      supervision. The REM-S is presented in detail along with specific examples and
      training and research suggestions. 

PMID- 25956952
TI  - Virtopsy Computed Tomography in Trauma: Normal Postmortem Changes and Pathologic
      Spectrum of Findings.
AB  - Virtopsy or virtual autopsy is an emerging technique, developed to supplement
      traditional forensic autopsy. Virtopsy can be done by using imaging techniques
      such as computed tomography (CT) and magnetic resonance imaging. Virtopsy CT
      comprises a pan-body noncontrast CT scan obtained after death. Virtopsy CT is
      useful in trauma cases as it can provide an overview of injuries sustained by the
      victim; detect craniofacial, cerebral, thoracic, and osseous injuries; and
      suggest putative causes of death. This can reduce the time taken for forensic
      autopsy and sometimes obviate the need for a forensic autopsy. However, virtopsy
      CT reporting is not exactly synonymous with interpreting antemortem contrast
      enhanced CT images as postmortem decompositional changes also occur. Awareness of
      imaging appearances of both postmortem putrefactive changes and pathologic
      findings is essential to avoid errors in interpretation and enable estimation of
      cause of death in patients with trauma. 

PMID- 25956953
TI  - Indole based peptidomimetics as anti-inflammatory and anti-hyperalgesic agents:
      Dual inhibition of 5-LOX and COX-2 enzymes.
AB  - The indoles bearing a tosyl group at N-1 and a dipeptide substituent at C-3 were
      screened for anti-inflammatory and anti-hyperalgesic activities. Some of the
      compounds made significant reduction in the dextran induced swelling and
      capsaicin induced pain in the albino mice. About 95% reversal in capsaicin
      induced pain occurred in the presence of 5 mg kg(-1) of compound 7b, 7d and 7h
      while diclofenac showed 90% reversal when its 10 mg kg(-1) dose was used. In
      order to examine the mode of action of these compounds; COX-1, COX-2 and 5-LOX
      enzyme immunoassays were performed. The IC50 of compound 7b for COX-2 and 5-LOX
      were in the nM range: 5-LOX, IC50 = 2.0 nM; COX-2, IC50 = 6.3 nM, selectivity for
      COX-2 over COX-1 was 351. The interactions of the compounds with COX-2 and 5-LOX
      were supported by the physical parameters including Ki, Ka and DeltaG. The most
      potent compounds 7b, 7d and 7h showed no toxicity to the animals and were
      identified as the promising leads for anti-inflammatory drugs. 

PMID- 25956954
TI  - A Prospective, Randomized Comparison of Intramuscular Phloroglucinol Versus Oral
      Misoprostol for Cervix Pretreatment Before Diagnostic Hysteroscopy.
AB  - The aim of this study was to compare the effectiveness and safety of
      intramuscular phloroglucinol and oral misoprostol for cervix pretreatment before
      diagnostic hysteroscopy. Several modalities for cervical priming and pain
      reduction have been adopted to reduce the complications related to cervical
      dilatation before hysteroscopy. Among them, the prostaglandin analog misoprostol
      is the most frequently used agent. Phloroglucinol, a spasmolytic, has also been
      showed to have an effect in inducing cervical dilatation but is rarely used
      before hysteroscopy. One hundred twenty outpatients undergoing anesthesia-free
      diagnostic hysteroscopy were randomly assigned to receive 80 mg intramuscular
      phloroglucinol and 400 mg oral misoprostol before diagnostic hysteroscopy. The
      main outcome measures were preoperative cervical width, visual analog scales
      (VAS) for pain, cervical passage time, and adverse reactions. Intramuscular
      phloroglucinol resulted in a significantly wider cervical width, lower VAS pain
      score, shorter cervical passage time, and a lower adverse effects rate compared
      with oral misoprostol. Intramuscular phloroglucinol is more effective and safer
      than oral misoprostol in inducing proper cervical priming and may be the optimal
      choice for cervical pretreatment before diagnostic hysteroscopy. 

PMID- 25956955
TI  - HaploShare: identification of extended haplotypes shared by cases and evaluation
      against controls.
AB  - Recent founder mutations may play important roles in complex diseases and
      Mendelian disorders. Detecting shared haplotypes that are identical by descent
      (IBD) could facilitate discovery of these mutations. Several programs address
      this, but are usually limited to detecting pair-wise shared haplotypes and not
      providing a comparison of cases and controls. We present a novel algorithm and
      software package, HaploShare, which detects extended haplotypes that are shared
      by multiple individuals, and allows comparisons between cases and controls.
      Testing on simulated and real cases demonstrated significant improvements in
      detection power and reduction of false positive rate by HaploShare relative to
      other programs. 

PMID- 25956956
TI  - Systemic glucocorticoid therapy: risk factors for reported adverse events and
      beliefs about the drug. A cross-sectional online survey of 820 patients.
AB  - Despite systemic glucocorticoids are widely used, risk factors for most of their
      adverse events and patients' beliefs about the drug are poorly known. An online
      survey was conducted between February and July 2013 through the website
      www.cortisone-info.fr . Demographic (e.g., age, gender) and therapeutic (e.g.,
      type of prescribed glucocorticoid, duration of prescription) data were collected.
      Patients were further asked to answer questions about glucocorticoid-induced
      adverse events and their beliefs about efficacy and safety of the drug. Risk
      factors for adverse events and efficacy/safety beliefs were assessed using
      multivariate logistic regression models. Eight hundred twenty questionnaires were
      analyzed (women 74.3 %; median age 49 [34-62] years, median equivalent prednisone
      dosage 20 [10-48] mg/day). The most frequently reported adverse events were
      insomnia (n = 477, 58.2 %), mood disturbances (n = 411, 50.1 %), hyperphagia (n =
      402, 49.0 %), and lipodystrophy (n = 387, 47.2 %). The risk of some adverse
      events (e.g., weight gain, easy bruising) increased with the duration of exposure
      while other adverse events (e.g., insomnia, mood disorders, epigastric pain) were
      present since the first days of exposure. The risk of hirsutism, altered wound
      healing, mood disturbances, weight gain, lipodystrophy, hyperphagia, and
      epigastric pain decreased with age. Cutaneous disorders, morphological changes,
      and epigastric pain were more frequently reported by women. Interestingly,
      patients prescribed prednisolone reported less adverse events than those
      prescribed prednisone. No adverse event, demographical or prescribing
      characteristics were associated with beliefs about efficacy while factors
      associated with safety concerns were age (OR: 1.2 [1.1-1.3] per 10-year
      increase), osteoporosis (OR: 3.3 [1.4-7.9]), easy bruising (OR: 1.6 [1.1-2.3]),
      insomnia (OR: 1.7 [1.2-2.4]), and weight gain (OR: 1.6 [1.1-2.2]). These results
      may help clinicians to adapt information speech, therapeutic education, and
      clinical and laboratory monitoring of patients prescribed glucocorticoid therapy.

PMID- 25956957
TI  - Is articular pain in rheumatoid arthritis correlated with ultrasound power
      Doppler findings?
AB  - OBJECTIVE: The study is addressed to determine if there is a correlation between
      intra-articular power Doppler (PD) and pain symptoms in patients with rheumatoid
      arthritis (RA). METHODS: A cross-sectional study of patients with established RA
      was rolled out. Seventy-two patients with chronic swelling at metacarpophalangeal
      (MCP) joints were consecutively enrolled in the study and divided into two groups
      (painful and painless). In the painful group, the inclusion criteria were pain in
      the visual analog scale (VAS), from 0 to 10 cm, of at least 4 cm and 0 in the
      painless group. All two to five MCP joints, bilaterally, were scanned by
      ultrasound (US) searching for intra-articular PD presence. Any value of p < 0.05
      was considered significant. RESULTS: Patients in the painful group had longer
      morning stiffness, worse 28-joint disease activity score (DAS 28), and health
      assessment questionnaire (HAQ) indexes. There were no association between pain
      and gray scale (GS) synovitis, odds ratio (OR) = 0.9 (0.6-1.2), p = 0.485; and
      pain and intra-articular PD, OR = 0.8 (0.6-1.2), p = 0.244. CONCLUSION: Intra
      articular PD was not correlated with pain symptom in this study.

PMID- 25956959
TI  - A Potential Immune Therapy for Mesothelioma.

PMID- 25956958
TI  - 18F-FDG PET/CT in a case of bilateral lacrimal gland infiltration by mantle cell
      lymphoma.

PMID- 25956960
TI  - Evaluating an ER Degrader for Breast Cancer.

PMID- 25956961
TI  - Sequence- vs. chip-assisted genomic selection: accurate biological information is
      advised.
AB  - BACKGROUND: The development of next-generation sequencing technologies (NGS) has
      made the use of whole-genome sequence data for routine genetic evaluations
      possible, which has triggered a considerable interest in animal and plant
      breeding fields. Here, we investigated whether complete or partial sequence data
      can improve upon existing SNP (single nucleotide polymorphism) array-based
      selection strategies by simulation using a mixed coalescence - gene-dropping
      approach. RESULTS: We simulated 20 or 100 causal mutations (quantitative trait
      nucleotides, QTN) within 65 predefined 'gene' regions, each 10 kb long, within a
      genome composed of ten 3-Mb chromosomes. We compared prediction accuracy by cross
      validation using a medium-density chip (7.5 k SNPs), a high-density (HD, 17 k)
      and sequence data (335 k). Genetic evaluation was based on a GBLUP method. The
      simulations showed: (1) a law of diminishing returns with increasing number of
      SNPs; (2) a modest effect of SNP ascertainment bias in arrays; (3) a small
      advantage of using whole-genome sequence data vs. HD arrays i.e. ~4%; (4) a minor
      effect of NGS errors except when imputation error rates are high (>=20%); and (5)
      if QTN were known, prediction accuracy approached 1. Since this is obviously
      unrealistic, we explored milder assumptions. We showed that, if all SNPs within
      causal genes were included in the prediction model, accuracy could also
      dramatically increase by ~40%. However, this criterion was highly sensitive to
      either misspecification (including wrong genes) or to the use of an incomplete
      gene list; in these cases, accuracy fell rapidly towards that reached when all
      SNPs from sequence data were blindly included in the model. CONCLUSIONS: Our
      study shows that, unless an accurate prior estimate on the functionality of SNPs
      can be included in the predictor, there is a law of diminishing returns with
      increasing SNP density. As a result, use of whole-genome sequence data may not
      result in a highly increased selection response over high-density genotyping.

PMID- 25956962
TI  - The adaptive human parental brain: implications for children's social
      development.
AB  - Although interest in the neurobiology of parent-infant bonding is a century old,
      neuroimaging of the human parental brain is recent. After summarizing current
      comparative research into the neurobiology of parenting, here I chart a global
      'parental caregiving' network that integrates conserved structures supporting
      mammalian caregiving with later-evolving networks and implicates parenting in the
      evolution of higher order social functions aimed at maximizing infant survival.
      The response of the parental brain to bonding-related behavior and hormones,
      particularly oxytocin, and increased postpartum brain plasticity demonstrate
      adaptation to infant stimuli, childrearing experiences, and cultural contexts.
      Mechanisms of biobehavioral synchrony by which the parental brain shapes, and is
      shaped by, infant physiology and behavior emphasize the brain basis of caregiving
      for the cross-generation transmission of human sociality. 

PMID- 25956963
TI  - Pacing for treatment and prevention of atrial fibrillation: Is there an end to
      this story?

PMID- 25956964
TI  - A prospective study of supraventricular activity and incidence of atrial
      fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) episodes are thought to be started by an
      electrical trigger reaching susceptible atria. Such a trigger could be present
      long before the occurrence of sustained symptomatic arrhythmia. OBJECTIVE: We
      sought to determine whether supraventricular extrasystoles (SVESs) and
      supraventricular tachycardias (SVTs) measured at 24-hour Holter electrocardiogram
      were associated with an increased incidence of AF. METHODS: In 1998-2000, 389
      individuals (44% men; mean age 65 years) were examined using 24-hour Holter
      electrocardiogram. Six individuals with known prevalent AF were excluded. After a
      mean follow-up of 10.3 years, there were 45 cases of incident AF. Hazard ratios
      (HRs) were computed using multivariable Cox regression adjusting for age, sex,
      systolic blood pressure, height, weight, smoking, and homeostatic model
      assessment of insulin resistance. RESULTS: Frequency of SVESs as well as SVT
      episodes per hour were independent predictors of incident AF (HR per log unit
      1.38; 95% confidence interval 1.14-1.68; P = .001 and HR 1.95; 95% confidence
      interval 1.21-3.13; P = .006, respectively). Further adjustment for education
      level, alcohol use, use of medication, and physical activity did not
      substantially alter the results, nor did analysis using competing risks
      regression accounting for a competing risk of death. The maximum duration of SVT
      or the heart rate at SVT was not significantly associated with the incidence of
      AF. CONCLUSION: SVESs and SVTs independently predict AF. The prognostic
      significance was similar for SVESs, SVTs, and a combination of the two. Repeated
      efforts to detect AF could be of merit in individuals with frequent
      supraventricular activity.

PMID- 25956965
TI  - Pacemaker implantation in pediatric heart transplant recipients: Predictors,
      outcomes, and impact on survival.
AB  - BACKGROUND: Little is known about the incidence of permanent pacemaker (PPM)
      implantation after heart transplantation (HTx) in the pediatric population.
      OBJECTIVE: The purpose of this study was to investigate the incidence,
      predictors, and outcomes of acute need for PPM implantation in pediatric HTx
      recipients. METHODS: We queried the United Network for Organ Sharing (UNOS)
      database for all pediatric (age <18 years) patients who received HTx (1994-2014).
      Regression models are reported for prediction of PPM implantation. RESULTS: A
      total of 6156 patients were analyzed, of whom 69 (1.1%) required posttransplant
      PPM implantation acutely. PPM use decreased over the study period (hazard ratio
      [HR] 0.95, P = .01). Compared with the non-PPM group, PPM group was more likely
      to be older (10 vs 5.0 years, P <.001), used antiarrhythmics (35.6% vs 18.3%, P =
      .006), required intraaortic balloon pump (2.9% vs 0.5%, P = .049), and had
      undergone biatrial anastomosis (68.1% vs 48.2%, P = .007). In a multivariable
      model, PPM implantation was predicted by higher donor age (HR 1.05, P = .002),
      biatrial anastomosis (HR 2.53, P = .04) and antiarrhythmic use (HR 2.12, P =
      .02). After adjusting for baseline characteristics, PPM recipients were at
      increased risk for posttransplant infection (47.8% vs 26.4%, P = .001) and
      dialysis (15.9% vs 6.6%, P = .003). Adjusted graft survival did not differ
      between the 2 groups (P = .78). CONCLUSION: Acute postoperative PPM implantation
      in pediatric HTx recipients is rare and has decreased over time. Acute PPM use is
      associated with biatrial anastomosis, antiarrhythmic use, and older donor age.
      Although PPM recipients had higher incidences of infections and dialysis, PPM
      implantation did not adversely impact survival.

PMID- 25956966
TI  - Stimulant therapy in children with attention-deficit/hyperactivity disorder and
      concomitant long QT syndrome: A safe combination?
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is prevalent in about
      11% of children in the United States. As such, ADHD is expected to be present in
      patients with long QT syndrome (LQTS), a rare, potentially lethal but highly
      treatable cardiac channelopathy. ADHD-directed stimulant therapy is relatively
      contraindicated in patients with LQTS because of concern for LQTS-triggered
      events. OBJECTIVE: The purpose of this study was to evaluate the ADHD-directed
      treatment, outcome, and frequency of LQTS-triggered events in patients with LQTS
      and concomitant ADHD. METHODS: A retrospective electronic medical record review
      of 357 pediatric patients with LQTS evaluated between 1999 and 2014 was performed
      to determine the prevalence of concomitant ADHD and the incidence of LQTS
      triggered events in patients with LQTS, with or without concomitant ADHD.
      RESULTS: Overall, 28 patients (8%) were diagnosed with LQTS concomitant ADHD.
      There were no phenotypic differences between patients with LQTS and ADHD, and
      LQTS alone. ADHD-directed stimulant therapy was stopped or advised against in 19
      patients (68%) at the time of first evaluation or after diagnosis. None of the 15
      stimulant-treated patients experienced LQTS-triggered events in a combined 56
      person-years of treatment. Perhaps paradoxically, there was a statistically lower
      LQTS-triggered event rate in the stimulant-treated ADHD group compared to the
      LQTS alone cohort. CONCLUSION: Among patients with mild- to moderate-risk LQTS,
      we found a prevalence of ADHD similar to that in the general population, which
      can be treated effectively and safely with stimulant therapy. Physicians should
      find reassurance in the low adverse event rate and should weigh the potential
      effects of suboptimal treatment of ADHD with the theoretical proarrhythmic risk
      from stimulant medications.

PMID- 25956967
TI  - Small-conductance Ca2+ -activated K+ channels and cardiac arrhythmias.
AB  - Small-conductance Ca2+ -activated K+ (SK, KCa2) channels are unique in that they
      are gated solely by changes in intracellular Ca2+ and, hence, function to
      integrate intracellular Ca2+ and membrane potentials on a beat-to-beat basis.
      Recent studies have provided evidence for the existence and functional
      significance of SK channels in the heart. Indeed, our knowledge of cardiac SK
      channels has been greatly expanded over the past decade. Interests in cardiac SK
      channels are further driven by recent studies suggesting the critical roles of SK
      channels in human atrial fibrillation, the SK channel as a possible novel
      therapeutic target in atrial arrhythmias, and upregulation of SK channels in
      heart failure in animal models and in human heart failure. However, there remain
      critical gaps in our knowledge. Specifically, blockade of SK channels in cardiac
      arrhythmias has been shown to be both antiarrhythmic and proarrhythmic. This
      contemporary review provides an overview of the literature on the role of cardiac
      SK channels in cardiac arrhythmias and serves as a discussion platform for the
      current clinical perspectives. At the translational level, development of SK
      channel blockers as a new therapeutic strategy in the treatment of atrial
      fibrillation and the possible proarrhythmic effects merit further considerations
      and investigations.

PMID- 25956968
TI  - Yishen Jiangzhuo Granules affect tubulointerstitial fibrosis via a mitochondrion
      mediated apoptotic pathway.
AB  - OBJECTIVE: To investigate the effect of Yishen Jiangzhuo Granules, YSJZG) on
      mitochondrial injury and regeneration and renal tubular epithelial cell apoptosis
      in chronic renal failure (CRF) rats and explore its mechanism from molecular
      pathology, gene, protein levels, and relative pathway. METHODS: The CRF rat model
      was established using 5/6 nephrectomy. Sixty rats were randomly divided into six
      groups: sham-operation group, model (CRF) group, Niaoduqing Granules-treated
      group [5 g/(kg.day)], low-, moderate-, and high-dose [L-YSJZG, M-YSJZG, H-YSJZG
      at 3, 6, and 9 g/(kg day)] YSJZG-treated group (n=10 each). The levels of serum
      creatinine (Scr), blood urea nitrogen (BUN), and 24-h urine protein were assessed
      after 10 weeks of treatment. The tubulointerstitial injury and collagen
      deposition were evaluated using periodic acid-schiff stain and Masson staining.
      Renal tubular epithelial cell apoptosis was assessed using the terminal
      deoxynucleotidyl transferase dUTP nick end labeling assay, mitochondrial injury
      was observed using an electron microscope, and superoxide dismutase (SOD),
      glutathione (GSH) and malondialdehyde (MDA) levels were assessed using
      chromometry. Transforming growth factor-beta1 (TGF-beta1) expression was assessed
      using immunohistochemistry. The expressions of Bax, Bcl-2, peroxisome
      proliferator-activated receptor gamma coactivator- 1alpha (PGC-1alpha),
      mitochondrial transcription factor A (Tfam), mitogen-activated protein kinases
      (MAPK) phosphorylation were evaluated by Western blot. RESULTS: YSJZG decreased
      the 24-h urine protein, BUN, Scr, remnant kidney weight-to-body weight ratio,
      renal tubular injury, deposition of collagen, and the apoptosis of renal tubular
      epithelial cells in a dose-dependent manner. YSJZG dose-dependently restored the
      number and structure of mitochondria and the expression of Tfam and PCG-1alpha,
      up-regulated the expression of Bcl-2, and inhibited the expression of Bax. YSJZG
      also dose-dependently inhibited TGF-beta1 expression, increased SOD and GSH
      activity, decreased the MDA level, and inhibited p38MAPK and pERK1/2
      phosphorylation (all P<0.01). CONCLUSION: YSJZG improved the renal function in
      rats with CRF and inhibited the progression of tubulointerstitial fibrosis by
      dose-dependently alleviating mitochondrial injury, restoring the expression of
      Tfam and PCG-1alpha, and inhibiting renal tubular epithelial cell apoptosis
      through inhibiting activation of reactive oxygen species-MAPK signaling.

PMID- 25956969
TI  - Vasorelaxation effect of gastrodin on isolated thoracic aorta rings of rats.
AB  - OBJECTIVE: To study the effect of gastrodin on isolated thoracic aorta rings of
      rats and to investigate the potential mechanism. METHODS: A perfusion model of
      isolated thoracic aorta rings of rats was applied. The effect of cumulative
      gastrodin (5, 50, 100,150, 200, and 250 MUmol/L) on endothelium-intact aorta
      rings was investigated. The same procedure was applied to observe the effect of
      gastrodin on endothelium-intact/denuded aorta rings pre-contracted with 10(-6)
      mol/L phenylephrine hydrochloride (PE). The aorta rings incubated by 200 mmol/L
      gastrodin in the Ca(2+)-free (K-H) solution was contracted by using PE. The
      effect of 200 mmol/L gastrodin on endothelium-denuded aorta rings pre-contracted
      with 60 mmol/L KCl was also observed. RESULTS: Compared with the denuded
      gastrodin group, the intact gastrodin group could significantly relax the PE
      contracted aorta rings (P<0.01). In Ca(2+)-free (K-H) solution KHS, the PE
      induced contraction rate of aorta rings pre-incubated by gastrodin was 6.5%+/
      0.7%, which was significantly less than the control group (11.8%+/-0.9%,P<0.01).
      However, after 3 mmol/L CaCl2 was added, the Ca(2+)-induced contraction in the
      gastrodin group (51.7%+/-2.4%) was similar to that in the control group (49.8%+/
      2.8%). The contractile rate of rings in the KCl-contracted gastrodin group
      (96.3%+/-0.6%) was not significantly different from that in the control group
      (96.8%+/-1.2%). CONCLUSIONS: Gastrodin has the effect of vasorelaxation on
      isolated thoracic aorta rings of rats. The mechanism of the vasorelaxation of
      gastrodin may mainly work through the inhibition of inositol 1, 4, 5
      trisphosphosphate receptor on the sarcoplasmic reticulum of the arterial smooth
      muscle, which leads to the reduction of the Ca(2+) released from the sarcoplasmic
      reticulum.

PMID- 25956971
TI  - Ambiguity between self and other: Individual differences in action attribution.
AB  - Individuals differ in their ability to attribute actions to self or other. This
      variance is thought to explain, in part, the experience of voice-hearing.
      Misattribution can also be context-driven. For example, causal ambiguity can
      arise when the actions of two or more individuals are coordinated and produce
      similar effects (e.g., music-making). Experience in such challenging contexts may
      refine skills of action attribution. Forty participants completed a novel finger
      tapping task which parametrically manipulated the proportion of control that
      'self' versus 'other' possessed over resulting auditory tones. Results showed
      that action misattribution peaked in the middle of the self-to-other continuum
      and was biased towards other. This pattern was related to both high hallucination
      proneness and to low musical-experience. Findings suggest not only that causal
      ambiguity plays a key role in agency but also that action attribution abilities
      may improve with practice, potentially providing an avenue for remediation of the
      positive symptoms of schizophrenia. 

PMID- 25956972
TI  - The assessment of parental stress and support in the neonatal intensive care unit
      using the Parent Stress Scale - Neonatal Intensive Care Unit.
AB  - PROBLEM: Parental stress in the neonatal intensive care unit (NICU) has been
      reported, however identifying modifiable stress factors and looking for
      demographic parent factors related to stress has not been well researched. AIM:
      This study aims to identify the most stressful elements for parents in the
      neonatal intensive care unit. METHODS: Parents of babies in an Australian
      neonatal intensive care unit (N=73) completed both the Parent Stress Scale -
      Neonatal Intensive Care Unit and a survey of parent and baby demographic and
      support experience variables (Parent Survey) over an 18-month period. FINDINGS:
      Older parental age, very premature birth and twin birth were significantly
      associated with a higher Parent Stress Scale - Neonatal Intensive Care Unit
      score. Having a high score in the Relationship and Parental Role scale was
      strongly associated with attendance at the parent support group. CONCLUSION:
      These results indicate the variables associated with stress and this knowledge
      can be used by teams within hospitals to provide better supportive emotional care
      for parents.

PMID- 25956970
TI  - Comparative analysis of mesenchymal stem cell and embryonic tendon progenitor
      cell response to embryonic tendon biochemical and mechanical factors.
AB  - INTRODUCTION: Advances in tendon engineering with mesenchymal stem cells (MSCs)
      are hindered by a need for cues to direct tenogenesis, and markers to assess
      tenogenic state. We examined the effects of factors involved in embryonic tendon
      development on adult MSCs, and compared MSC responses to that of embryonic tendon
      progenitor cells (TPCs), a model system of tenogenically differentiating cells.
      METHODS: Murine MSCs and TPCs subjected to cyclic tensile loading, transforming
      growth factor-beta2 (TGFbeta2), and fibroblast growth factor-4 (FGF4) in vitro
      were assessed for proliferation and mRNA levels of scleraxis, TGFbeta2,
      tenomodulin, collagen type I and elastin. RESULTS: Before treatment, scleraxis
      and elastin levels in MSCs were lower than in TPCs, while other tendon markers
      expressed at similar levels in MSCs as TPCs. TGFbeta2 alone and combined with
      loading were tenogenic based on increased scleraxis levels in both MSCs and TPCs.
      Loading alone had minimal effect. FGF4 downregulated tendon marker levels in MSCs
      but not in TPCs. Select tendon markers were not consistently upregulated with
      scleraxis, demonstrating the importance of characterizing a profile of markers.
      CONCLUSIONS: Similar responses as TPCs to specific treatments suggest MSCs have
      tenogenic potential. Potentially shared mechanisms of cell function between MSCs
      and TPCs should be investigated in longer term studies.

PMID- 25956973
TI  - Principles of chromatin organization in yeast: relevance of polymer models to
      describe nuclear organization and dynamics.
AB  - Nuclear organization can impact on all aspects of the genome life cycle. This
      organization is thoroughly investigated by advanced imaging and chromosome
      conformation capture techniques, providing considerable amount of datasets
      describing the spatial organization of chromosomes. In this review, we will focus
      on polymer models to describe chromosome statics and dynamics in the yeast
      Saccharomyces cerevisiae. We suggest that the equilibrium configuration of a
      polymer chain tethered at both ends and placed in a confined volume is consistent
      with the current literature, implying that local chromatin interactions play a
      secondary role in yeast nuclear organization. Future challenges are to reach an
      integrated multi-scale description of yeast chromosome organization, which is
      crucially needed to improve our understanding of the regulation of genomic
      transaction. 

PMID- 25956974
TI  - CD4+ T cell polyfunctional profile in HIV-TB coinfection are similar between
      individuals with latent and active TB infection.
AB  - CD4+ T cell counts of HIV-infected individuals with pulmonary TB (PTB) are higher
      than with other opportunistic infections suggesting that progression to PTB is
      not merely due to T cell depletion but also dysfunction. There are limited data
      examining T cell functional signatures in human HIV-TB co-infection particularly
      in PTB which accounts for about 80% of active TB disease overall. We examined a
      cohort of HIV-infected anti-retroviral naive individuals in Kampala, Uganda, a TB
      endemic area using multiparametric flow cytometry analysis to determine IFN
      gamma, IL-2, IL-17, and TNF-alpha production in CD4+ memory T cell subsets. The
      cytokine frequency and polyfunctionality profile of Mycobacterium tuberculosis
      (MTB)-specific CD4+ T cells in HIV-infected persons with latent TB infection
      (LTBI) or PTB is comparable. This similarity suggests that LTBI may represent a
      smoldering state of persistent MTB replication rather than dormant infection.
      This may be a contributory mechanism to the significantly increased risk of
      progression to PTB in this population. 

PMID- 25956975
TI  - Involvement of cAMP-PKA pathway in adenosine A1 and A2A receptor-mediated
      regulation of acetaldehyde-induced activation of HSCs.
AB  - The present study was undertaken to investigate the mechanism by which adenosine
      receptors (ARs)-mediated the cAMP/PKA/CREB signal pathway regulates the
      activation of acetaldehyde-induced hepatic stellate cells (HSCs). Primary HSCs
      were isolated from SD rats, cultured in vitro, and activated with different
      concentrations of acetaldehyde at different time points. Quantitative real-time
      PCR and Western blotting were used to quantify both protein and mRNA levels of
      the four AR (A1R, A2AR, A2BR, and A3R) in rat HSCs. Selective inhibitors of PDEs
      and the Gi/o protein pathway, general AR agonists, and AR subtype specific agents
      were used to study the AR signaling. The level of cAMP was measured by radio
      immunoassay, and the expression of alpha-SMA, collagen type I and III, PKA and p
      CREB were also detected by Western blotting. Acetaldehyde could significantly
      promote HSC proliferation, with a maximum stimulatory effect observed at 48 h
      after exposure to 200 MUM acetaldehyde. All four AR subtypes could be present in
      rat HSCs, and the mRNA and protein expression levels for A2AR and A1R in much
      greater abundance than those for A2BR and A3R. The expression of A2AR and A1R was
      significantly increased in acetaldehyde-induced HSCs as compared with that of
      control group, whereas the expression of A2BR and A3R remained unaffected by the
      addition of acetaldehyde. Curiously, there is coupling of A2AR to the Gs-AC
      signaling, as well as coupling of A1R to the Gi/o-AC signaling pathway in
      acetaldehyde-induced HSCs. Both the A2AR and A1R antagonists could suppress the
      activation of HSC, although they have opposing effects on cAMP signal
      transduction. These results suggested that a combination of cAMP/PKA/CREB signals
      via A2AR and A1R likely mediate the activation of acetaldehyde-induced HSCs, and
      A1R coupled to the Gi/o-AC signaling pathway may be masked by the more
      predominant A2AR that coupled to the Gs-AC signaling pathway.

PMID- 25956976
TI  - Non-coding transcription by RNA polymerase II in yeast: Hasard or necessite?
AB  - Recent developments of microarrays and deep sequencing techniques have unveiled
      an unexpected complexity of the eukaryotic transcriptome, demonstrating that
      virtualy the entire genome is transcribed by RNA polymerase II (RNAPII).
      Transcription occurring outside of annotated regions is generally referred to as
      pervasive transcription and leads to the production of several classes of non
      coding RNAs (ncRNAs). In this review we will discuss the metabolism and
      functional significance of these ncRNAs in the yeast Saccharomyces cerevisiae. We
      will discuss the mechanisms that the cell has adopted to prevent potentially
      disruptive interference between pervasive transcription and the expression of
      canonical genes. We will explore the possible reasons that justify the
      evolutionary conserved maintenance of extensive genomic transcription. 

PMID- 25956977
TI  - Characterization and expression analysis of Calmodulin (CaM) in orange-spotted
      grouper (Epinephelus coioides) in response to Vibrio alginolyticus challenge.
AB  - Vibrio alginolyticus containing the highly toxic extracellular product is one of
      the most serious threats to grouper survival and its minimum lethal dose is
      approximately 500 CFU/g fish body weight in grouper. To study the toxic effects
      of V. alginolyticus on the immune system in teleost, Calmodulin (CaM), an
      important molecular indicator gene, was cloned from the orange-spotted grouper
      (Epinephelus coioides). The full-length Ec-CaM consisted of a 5'-UTR of 103 bp,
      an ORF of 450 bp and a 3'-UTR of 104 bp. The Ec-CaM gene encoded a protein of 149
      amino acids with an estimated molecular mass of 16.4 kDa and a predicted
      isoelectric point of 3.93. The deduced amino acid sequence showed that Ec-CaM
      contained four highly conserved EF-hand domains known to be critical for the
      function of CaM. Ec-CaM was widely expressed and the highest expression level was
      observed in liver. Following V. alginolyticus challenge, a sharp increase level
      of respiratory burst activity and apoptosis ratio were observed. Further analyses
      of CaM expression and p53 expression in liver, kidney and spleen by qRT-PCR
      demonstrated that the up-regulated expression of CaM and p53 were observed in the
      vibrio challenge group. Western blotting analysis confirmed that the Ec-CaM
      protein was strongly induced in liver at 12 h post-injection, while a sharp
      increase of p53 protein expression was observed at 24 h post-injection. These
      results showed CaM expression serving as a potential molecular indicator may help
      to assess the toxicological effects of V. alginolyticus on the ROS generation and
      apoptotic process in grouper.

PMID- 25956978
TI  - Interactive effects of sulfur and chromium on antioxidative defense systems and
      BnMP1 gene expression in canola (Brassica napus L.) cultivars differing in Cr(VI)
      tolerance.
AB  - Plants suffer with combined stress of sulfur (S) deficiency and hexavalent
      chromium [Cr(VI)] in soils. There are a few reports on the interactive effects of
      S-deficiency and Cr(VI) stress. Therefore, the interactions between S nutrition
      and Cr(VI) stress were investigated in hydroponically grown canola (Brassica
      napus L.) cultivars differing in Cr(VI) tolerance. The relatively Cr(VI)-tolerant
      (NK Petrol) and Cr(VI)-susceptible (Sary) cultivars were grown in S-sufficient
      nutrient solution and then exposed to variable S concentrations [deficient (0 mM
      S, -S) and sufficient (1 mM S, +S)]. The seedlings were then exposed to 100 MUM
      Cr(VI) for 3 days. S-deficiency (-S/-Cr) and combined stress (-S/+Cr) caused a
      significant decrease in growth parameters of Sary than NK Petrol (P < 0.05). In 
      S/+Cr treatment, Cr accumulation in Sary was significantly higher than NK Petrol.
      The higher level of Cr in Sary increased lipid peroxidation and decreased
      chlorophyll content. The activities of antioxidant enzymes and cysteine content
      were significantly higher in NK Petrol than in Sary under combined stress. The
      levels of ascorbate (AsA) and glutathione (GSH) were significantly decreased by S
      deficiency. The expression level of metallothionein gene (BnMP1) in the tolerant
      NK Petrol was increased by -S/+Cr treatment. However, expression level of BnMP1
      gene in the susceptible Sary was enhanced by +S/+Cr treatment. This result
      suggests metallothionein (MT) may be involved in Cr(VI) tolerance under S
      deficient condition. In conclusion, S nutrition influenced Cr accumulation and
      enhanced tolerance caused by a positive effect on defense systems and gene
      expression.

PMID- 25956979
TI  - Physiological and biochemical response to drought stress in the leaves of
      Aegiceras corniculatum and Kandelia obovata.
AB  - Drought stress is one of the major abiotic stresses that affects plant growth and
      metabolism adversely around the world. According to this research, the effect of
      drought stress on the activity of antioxidative enzymes, soluble sugar, protein
      and lipid peroxidation were studied in leaves of two mangrove plants, Kandelia
      obovata and Aegiceras corniculatum. The result showed that superoxide dismutase
      (SOD) and peroxidase (POD) varied significantly between the leaves and roots
      studied. The activities increased in different stress levels. The production rate
      of O 2 (-.) changed with the activity of SOD and POD. Lipid peroxidation was
      enhanced and Glycine betaine (GB) could decrease the level of malonaldehyde in
      order to reduce the damage of membrane system. The content of soluble sugar and
      protein also increased under drought stress and GB helped to eliminate the
      accumulation of them which somehow enhance the ability of defensing the plants
      under drought stress. These results indicated that antioxidative activity may
      play an important role in A. corniculatum and K. obovata and that cell membrane
      in leaves of K. obovata had greater stability than those of A. corniculatum.
      Exogenous application of GB had positive effects on A. corniculatum and K.
      obovata under drought stress which could be products exogenously applied to
      mangrove plants in order to alleviates the adverse effects.

PMID- 25956981
TI  - Spatial and vertical distribution of bacterial community in the northern South
      China Sea.
AB  - Microbial communities are highly diverse in coastal oceans and response rapidly
      with changing environments. Learning about this will help us understand the
      ecology of microbial populations in marine ecosystems. This study aimed to assess
      the spatial and vertical distributions of the bacterial community in the northern
      South China Sea. Multi-dimensional scaling analyses revealed structural
      differences of the bacterial community among sampling sites and vertical depth.
      Result also indicated that bacterial community in most sites had higher diversity
      in 0-75 m depths than those in 100-200 m depths. Bacterial community of samples
      was positively correlation with salinity and depth, whereas was negatively
      correlation with temperature. Proteobacteria and Cyanobacteria were the dominant
      groups, which accounted for the majority of sequences. The alpha-Proteobacteria
      was highly diverse, and sequences belonged to Rhodobacterales bacteria were
      dominant in all characterized sequences. The current data indicate that the
      Rhodobacterales bacteria, especially Roseobacter clade are the diverse group in
      the tropical waters.

PMID- 25956980
TI  - Spatial variation of phytoplankton community structure in Daya Bay, China.
AB  - Daya Bay is one of the largest and most important gulfs in the southern coast of
      China, in the northern part of the South China Sea. The phylogenetic diversity
      and spatial distribution of phytoplankton from the Daya Bay surface water and the
      relationship with the in situ water environment were investigated by the clone
      library of the large subunit of ribulose-1, 5-bisphosphate carboxylase (rbcL)
      gene. The dominant species of phytoplankton were diatoms and eustigmatophytes,
      which accounted for 81.9 % of all the clones of the rbcL genes. Prymnesiophytes
      were widely spread and wide varieties lived in Daya Bay, whereas the quantity was
      limited. The community structure of phytoplankton was shaped by pH and salinity
      and the concentration of silicate, phosphorus and nitrite. The phytoplankton
      biomass was significantly positively affected by phosphorus and nitrite but
      negatively by salinity and pH. Therefore, the phytoplankton distribution and
      biomass from Daya Bay were doubly affected by anthropic activities and natural
      factors.

PMID- 25956982
TI  - Pb uptake and tolerance in the two selected mangroves with different root
      lignification and suberization.
AB  - Metal pollution has been widely reported in mangrove wetlands; however, the
      mechanisms involved in metal detoxification by mangroves are still poorly
      understood. This study aimed to investigate the possible function of root
      lignification/suberization on Pb uptake and tolerance in mangroves. Two
      mangroves, Acanthus ilicifolius and Rhizophora stylosa with different root
      lignification/suberization were selected as plant materials; the former exhibits
      a thin exodermis and low lignification/suberization, while the latter possesses a
      thick exodermis and high lignification/suberization. A pot trial with addition of
      Pb was conducted to investigate the differences in Pb uptake and tolerance
      between the two mangroves. The experiment of rhizobox was designed to explore Pb
      dynamics and availabilities in the rhizosphere soils, besides, the ability of Pb
      uptake by the excised roots and X-ray analysis for Pb distribution within roots
      were also detected. The results revealed that R. stylosa exhibited relatively
      higher Pb tolerance together with less Pb accumulations when compared to A.
      ilicifolius. For both species, lower proportion of exchangeable and Carbonate Pb
      and higher higher Fe-Mn oxides Pb were observed in the rhizosphere zone when
      compared to the respective non-rhizosphere zone. The results from metal uptake by
      the excised roots and X-ray analysis clearly showed that the thick
      lignified/suberized exodermis of R. stylosa could more efficiently delay Pb
      entering into the roots, leading to less Pb accumulation. In summary, the present
      study proposes a barrier property of the lignified/suberized exodermis in dealing
      with the stresses of Pb.

PMID- 25956983
TI  - Differences in root aeration, iron plaque formation and waterlogging tolerance in
      six mangroves along a continues tidal gradient.
AB  - Mangrove is a special coastal forest along tropical and subtropical intertidal
      shores. However, how mangroves adapt to tidal flooding and the mechanisms
      involved in mangrove zonation are still poorly understood. In this study, a pot
      trial with different tide treatments was conducted to investigate the differences
      in root anatomy, porosity, radial oxygen loss, iron plaque formation and
      waterlogging tolerance among six mangroves along a continuous tidal gradient. The
      index of waterlogging tolerance illustrated that Sonneratia apetala possessed the
      highest index, followed by Aeguceras corniculatum/Kandelia, Rhizophora stylosa,
      Heritiera littorlis and Thespesia populnea. Waterlogging tolerances of the
      mangroves were found to be positively correlated with their root porosity, radial
      oxygen loss and iron plaque formation. Waterlogging-sensitive species such as
      landward semi-mangroves exhibited small root porosity and ROL, while waterlogging
      tolerant species such as seaward pioneer and rhizophoraceous mangroves exhibited
      extensive porosity, ROL and iron plaque formation. Nevertheless, grater root
      porosity and iron plaque formation were detected in permanent waterlogged plants
      when compared to drained plants. In conclusion, The present study proposes a
      structural adaptive strategy to tidal flooding in mangroves, such that the
      mangroves with higher root porosity, ROL and iron plaque appeared to exhibit
      higher waterlogging tolerance and adaptability in anaerobic foreshores.

PMID- 25956984
TI  - Geographical distribution and risk assessment of persistent organic pollutants in
      golden threads (Nemipterus virgatus) from the northern South China Sea.
AB  - Fish are often used as good bioindicators to monitor the occurrence of persistent
      organic pollutants (POPs) on different scales in recent years. Forty-five golden
      threads (Nemipterus virgatus) were collected from six sampling sites in the
      northern South China Sea (SCS) to investigate the geographical distribution of
      polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs),
      dichlorodiphenyltrichloroethane and its metabolites (DDTs). Concentrations of
      PBDEs, PCBs, and DDTs ranged from 1.3-36.0, 2.3-76.5, 8.3-228 ng/g lipid weight,
      respectively. The highest PBDEs and DDTs concentrations were found in golden
      threads from Shantou, owing to the intensive electronic waste recycling
      activities and rapid development of agriculture. Samples from Haikou had the
      highest levels of PCBs, probably due to the existence of many shipbuilding yards
      in the past years. The concentrations of PBDEs and PCBs were found in a
      decreasing trend from east to west and from north to south, while DDTs
      concentrations had no obvious trend in the distribution. PCBs were the most
      prevalent contaminants in Xiamen and Yangjiang, while DDTs were the dominant
      compounds at the other four sampling sites. Different profiles of POPs at each
      sampling site may attribute to different pollution sources in the northern SCS.
      Ratios of (DDD + DDE)/DDTs in golden threads suggested the probability of fresh
      input of DDT in the northern SCS. The estimated daily intakes of PBDEs, PCBs and
      DDTs were 0.030-0.069, 0.167-0.258 and 0.105-1.88 ng/kg/day, respectively, which
      were significantly lower than the acceptable daily intake, suggesting that
      consumption of golden threads from the northern SCS would not subject the
      residents in the coastal areas of SCS to significant health risk.

PMID- 25956985
TI  - Glucosamine: fructose-6-phosphate amidotransferase in the white shrimp
      Litopenaeus vannamei: characterization and regulation under alkaline and cadmium
      stress.
AB  - Heavy metal residues and chemical contaminators considered as relevant sources of
      aquatic environmental pollutants have a generally immunosuppressive effect on
      aquatic organisms, depressing metabolic activities and immune response.
      Glutamine: fructose-6-phosphate aminotransferase (GFAT, EC2.6.1.16) is the first,
      and rate-limiting, enzyme in the hexosamine biosynthetic pathway, and is involved
      in the regulation of chitin biosynthesis and glycosylation of proteins. We have
      isolated and characterized GFAT from the white shrimp Litopenaeus vannamei. Amino
      acid sequence similarity of the Lv-GFAT (L.vannamei-GFAT) was highest to GFATs
      isolated from insects and mammals (83 % similarity to that of Haemaphysalis
      longicornis). The open-reading frame of the Lv-GFAT codes for a protein of 41.6
      kDa with a calculated isoelectric point of 5.03. RT-PCR assays showed that
      endogenous Lv-GFAT mRNA is most strongly expressed in the intestine. Further
      analysis of Lv-GFAT gene expression in hepatopancreas by quantitative real-time
      PCR demonstrated that Lv-GFAT transcript levels increased when the shrimp were
      exposed to alkaline pH (9.3) and cadmium stress, but the time when its mRNA
      expression level peaked differed under these stresses. We also first expressed
      the recombinant protein of GFAT from shrimps in Escherichia coli. Western blot
      analyses confirmed that the Lv-GFAT protein was strongly expressed in the
      hepatopancreas after exposure to the LC-Cd stress. These results suggest that Lv
      GFAT expression is stimulated by alkaline pH and cadmium stress and that it may
      play important roles in resistance of shrimp to environmental stresses.

PMID- 25956986
TI  - Genetics and mechanism of resistance to deltamethrin in the house fly, Musca
      domestica L., from Pakistan.
AB  - Deltamethrin (a pyrethroid insecticide) has widely been used against the house
      fly, Musca domestica, a pest found in livestock facilities worldwide. Although,
      cases of both metabolic and physiological resistance to deltamethrin have been
      reported in different parts of the world, no studies have been reported to
      characterize this resistance in house flies from Pakistan. In the present study,
      we investigated a field strain of house flies for potential to develop resistance
      to deltamethrin. Also, its stability, possible mechanisms and cross-resistance
      potential to other insecticides. Before the selection experiments, the field
      strain showed 8.41-, 3.65-, 8.39-, 2.68-, 19.17- and 5.96-fold resistance to
      deltamethrin, bifenthrin, lambda-cyhalothrin, chlorpyrifos, profenofos and
      spinosad, respectively, compared with the reference strain (Lab-susceptible).
      Continuous selection of the field strain (Delta-SEL) with deltamethrin for six
      generations (G1-G6) in the laboratory increased the resistance ratio to 176.34
      after bioassay at G7. The Delta-SEL strain was reared for the next four
      generations without exposure to deltamethrin and bioassayed at G11 which revealed
      that the resistance was stable. The Delta-SEL strain at G7 showed cross
      resistance to all other insecticides except spinosad, when compared to the
      bioassays before the selection experiment (G1). Crosses between Delta-SEL and Lab
      susceptible strains revealed an autosomal and incomplete dominant mode of
      resistance to deltamethrin. A direct test using a monogenic inheritance model
      revealed that the resistance was governed by more than one factor. Moreover,
      synergism studies with the enzyme inhibitors PBO and DEF reduced the resistance
      to deltamethrin in the selected strain up to 2.51- and 2.19-fold, respectively,
      which revealed that the resistance was possibly due to microsomal oxidase and
      esterase activity. It is concluded that the resistance to deltamethrin was
      autosomal and incompletely dominant. The high cross-resistance of bifenthrin,
      lambda-cyhalothrin, chlorpyrifos and profenofos in the Delta-SEL strain suggests
      that other insecticides would be necessary to counter the resistance. These
      results are therefore suggestive for implications in the management of
      insecticide resistance in house flies. 

PMID- 25956987
TI  - Differential roles of inflammation and apoptosis in initiation of mid-gestational
      abortion in malaria-infected C57BL/6 and A/J mice.
AB  - INTRODUCTION: Plasmodium chabaudi AS-infection in pregnant A/J and C57BL/6J mice
      results in mid-gestational pregnancy loss. Although associated with increased
      systemic and placental pro-inflammatory responses and coagulopathy, the molecular
      mechanisms that underlie poor pregnancy outcomes in these mice are not yet fully
      understood. This study investigates the relationships between inflammation,
      apoptosis and malaria-induced pregnancy loss. METHODS: Infection with P. chabaudi
      AS in early murine pregnancy and term human placental tissues from an endemic
      setting were assessed by histology, immunohistochemistry, TUNEL staining, real
      time PCR, flow cytometry, western blot, and ELISA. RESULTS: Quantitative PCR
      reveals accumulation of lymphocytes and monocytes and upregulation of chemokines
      that attract these cell types in malaria-exposed mid-gestational A/J conceptuses.
      Monocyte accumulation is confirmed by flow cytometry and placental
      immunohistochemistry. Concurrent with initiation of malaria-induced abortion,
      markers of apoptosis are evident in the junctional zone, but not the labyrinth,
      of A/J placentae. In contrast, mid-gestation conceptuses in infected C57BL/6J
      lack evidence for monocyte accumulation, exhibiting low or no in situ placental
      staining despite trophoblast immunoreactivity for the monokine, CCL2.
      Additionally, placental apoptosis is not consistently observed, and when evident,
      appears after malaria-induced abortion typically initiates. Similarly,
      trophoblast apoptosis in term human placental malaria is not observed. Of those
      studied, a sole common feature of malaria-induced abortion in A/J and C57BL/6J
      mice is elevation of plasma tumor necrosis factor. DISCUSSION: Consistent with
      our previous observations, tumor necrosis factor is likely to be a central driver
      of malaria-induced pregnancy loss in both strains, but likely operates through
      mechanisms distinct from placental apoptosis in C57BL/6J mice.

PMID- 25956988
TI  - Hypoxia is an effective stimulus for vesicular release of ATP from human
      umbilical vein endothelial cells.
AB  - INTRODUCTION: Hypoxia induces dilatation of the umbilical vein by releasing
      autocoids from endothelium; prostaglandins (PGs), adenosine and nitric oxide (NO)
      have been implicated. ATP is vasoactive, thus we tested whether hypoxia releases
      ATP from primary Human Umbilical Vein Endothelial Cells (HUVEC). METHODS: HUVEC
      were grown on inserts under no-flow conditions. ATP was assayed by luciferin
      luciferase and visualised by quinacrine labeling. Intracellular Ca(2+)
      ([Ca(2+)]i) was imaged with Fura-2. RESULTS: ATP release occurred constitutively
      and was increased by hypoxia (PO2: 150-8 mmHg), ~10-fold more from apical, than
      basolateral surface. Constitutive ATP release was decreased, while hypoxia
      induced release was abolished by brefeldin or monensin A, inhibitors of vesicular
      transport, and LY294002 or Y27632, inhibitors of phosphoinositide 3-kinases
      (PI3K) and Rho-associated protein kinase (ROCK). ATP release was unaffected by NO
      donor, but increased by calcium ionophore, by >60-fold from apical, but <25% from
      basolateral surface. Hypoxia induced a small increase in [Ca(2+)]i compared with
      ATP (10 MUM); hypoxia inhibited the ATP response. Quinacrine-ATP fluorescent loci
      in the perinuclear space, were diminished by hypoxia and monensin, whereas
      brefeldin A increased fluorescence intensity, consistent with inhibition of
      anterograde transport. DISCUSSION: Hypoxia within the physiological range
      releases ATP from HUVEC, particularly from apical/adluminal surfaces by
      exocytosis, via an increase in [Ca(2+)]i, PI3K and ROCK, independently of NO. We
      propose that hypoxia releases ATP at concentrations sufficient to induce
      umbilical vein dilation via PGs and NO and improve fetal blood flow, but curbs
      amplification of ATP release by autocrine actions of ATP, so limiting its pro
      inflammatory effects.

PMID- 25956989
TI  - Caring for dementia: a population-based study examining variations in guideline
      consistent medical care.
AB  - BACKGROUND: Evidence indicates that early detection and management of dementia
      care can improve outcomes. We assess variations in dementia care based on
      processes outlined in clinical guidelines by the BC Ministry of Health. METHOD: A
      population-based retrospective cohort study of community-dwelling seniors using
      patient-level administrative data in British Columbia, Canada. Guidelines
      measured: laboratory testing, imaging, prescriptions, complete examination,
      counseling, and specialist referral. RESULTS: Older patients were less likely to
      receive guideline-consistent medical care. Patients in higher income categories
      had higher odds of receiving counseling (confidence interval or CI 1.13-153) and
      referrals (15.1 CI 1.18-1.95) compared with those of lower income. Over a quarter
      of the cohort received an antipsychotic (28%) or nonrecommended benzodiazepine
      (26%). Individuals living within "rural" health authorities or of low income were
      more likely to receive antipsychotic treatment. CONCLUSION: Patterns of
      inequality by age and income may signal barriers to care, particularly for
      management of dementia care processes.

PMID- 25956990
TI  - Cortical microinfarcts on 3T MRI: Clinical correlates in memory-clinic patients.
AB  - INTRODUCTION: This is the first study to assess cerebral microinfarcts (CMIs) on
      3 tesla (3T) magnetic resonance imaging (MRI) in a memory clinic population.
      METHODS: We included 238 consecutive patients (aged 72.5 +/- 9.1 years) from a
      memory clinic in Singapore. All patients underwent extensive neurological and
      neuropsychological testing and 3T MRI on the same day. Cortical CMI rating
      criteria were adapted from a previous study on 7T MRI. We analyzed the frequency
      and association of cortical CMIs with demographic, clinical, cognition, and other
      MRI findings. RESULTS: Seventy-five patients (32%) had cortical CMIs (median 1,
      range 1-43). Patients with CMIs showed worse cognitive functioning on MMSE, and
      in the domains of language and visuoconstruction. The presence of CMIs was
      related to other markers of small vessel disease, but most strongly larger
      cortical infarcts. Patients with CMIs were more often diagnosed with vascular
      dementia. DISCUSSION: Cortical CMIs on 3T MRI are a novel marker of
      cerebrovascular disease in dementia.

PMID- 25956991
TI  - Sex differences in immune responses to infectious diseases.
AB  - PURPOSE: The influence of sex hormones is recognized to account for the
      susceptibility and distinct outcomes of diverse infectious diseases. METHODS:
      This review discusses several variables including differences in behavior and
      exposure to pathogens, genetic, and immunological factors. CONCLUSION:
      Understanding sex-based differences in immunity during different infectious
      diseases is crucial in order to provide optimal disease management for both
      sexes.

PMID- 25956992
TI  - Stabilization of Alpha-Synuclein Oligomers In Vitro by the Neurotransmitters,
      Dopamine and Norepinephrine: The Effect of Oxidized Catecholamines.
AB  - Aggregation of the protein alpha-synuclein has been identified in the
      pathogenesis of Parkinson's disease and is initiated by the folding of the
      protein monomer into an amyloid form of insoluble fibrils. The neurotransmitters
      dopamine and norepinephrine have been shown to both inhibit the formation of
      these fibrils and disaggregate existing fibrils, yielding the more toxic
      oligomeric form of alpha-synuclein. This study characterizes the stable oligomers
      formed through the aggregation and disaggregation processes in the presence of
      these catecholamines, and suggests differences in oligomer formation depending on
      the extent of oxidation of the neurotransmitter at the time of oligomerization.
      Unique oligomers are also stabilized, likely formed from the aggregation of
      monomeric alpha-synuclein and a proteolytic fragment of alpha-synuclein; however,
      proteolytic fragments do not form as readily in the presence of these
      neurotransmitters. These findings suggest novel pathways for the formation of
      alpha-synuclein oligomers in the presence of neurotransmitters, particularly
      oxidized forms. 

PMID- 25956994
TI  - TNF-alpha stimulates MMP-3 production via PGE2 signalling through the NF-kB and
      p38 MAPK pathway in a murine cementoblast cell line.
AB  - BACKGROUND: Cementoblasts are considered to play an important role in the
      homeostasis of periodontal tissues under both physiologic and pathologic
      conditions. Matrix metalloproteinases (MMPs) is the key family of enzymes
      participating in extracellular matrix remodelling. In the present study, the
      effects and regulatory mechanisms of tumour necrosis factor (TNF)-alpha on the
      expression of MMPs and their inhibitors (tissue inhibitor of metalloproteinases;
      TIMPs) were investigated. MATERIALS AND METHODS: OCCM-30, an immortalised murine
      cementoblast cell line, was stimulated with TNF-alpha at 1 and 10ng/ml for 24h.
      The expression of Mmp-2, Mmp-3, Mmp-13, Mmp-14, Timp-1, and Timp-2 as well as
      PGE2 was determined. Inhibitors of MAPKs, PI3K/Akt, NF-kB and Cox-2 were employed
      to reveal possible TNF-alpha induced regulatory signalling pathway(s). The mRNA
      and protein expression were analysed by (semi)quantitative real-time PCR and
      enzyme-linked immunosorbent assay (ELISA), respectively. RESULTS: TNF-alpha dose
      dependently stimulated MMP-3 expression by cementoblasts. This was found for mRNA
      as well as protein expression. No significant differences were found in the mRNA
      expression of Mmp-2, Mmp-13, Mmp-14, Timp-1, and Timp-2 upon TNF-alpha
      stimulation. The level of PGE2, however, was significantly increased along with
      MMP-3. Treatment with a selective Cox-2 inhibitor resulted in partial suppression
      of TNF-alpha-induced Mmp-3 mRNA expression. Addition of PGE2 enhanced Mmp-3 mRNA
      in a dose dependent manner, suggesting an inductive effect of TNF-alpha partly
      via PGE2. The up-regulation of Mmp-3 by TNF-alpha was completely suppressed by a
      combination of NF-kB and p38 MAPK inhibitors, while partial suppression was found
      with each inhibitor. The effect of PGE2 on Mmp-3 expression was abolished by
      treating cells with an NF-kB inhibitor; a p38 MAPK inhibitor had only a small
      effect. CONCLUSIONS: The present study indicates that cementoblasts respond to
      TNF-alpha by increasing MMP-3 production partially via PGE2 and signalling
      through the NF-kB and p38 MAPK pathway. MMP-3 may participate in periodontal
      tissue degradation/remodelling.

PMID- 25956993
TI  - Capillary dysfunction: its detection and causative role in dementias and stroke.
AB  - In acute ischemic stroke, critical hypoperfusion is a frequent cause of hypoxic
      tissue injury: As cerebral blood flow (CBF) falls below the ischemic threshold of
      20 mL/100 mL/min, neurological symptoms develop and hypoxic tissue injury evolves
      within minutes or hours unless the oxygen supply is restored. But is ischemia the
      only hemodynamic source of hypoxic tissue injury? Reanalyses of the equations we
      traditionally use to describe the relation between CBF and tissue oxygenation
      suggest that capillary flow patterns are crucial for the efficient extraction of
      oxygen: without close capillary flow control, "functional shunts" tend to form
      and some of the blood's oxygen content in effect becomes inaccessible to tissue.
      This phenomenon raises several questions: Are there in fact two hemodynamic
      causes of tissue hypoxia: Limited blood supply (ischemia) and limited oxygen
      extraction due to capillary dysfunction? If so, how do we distinguish the two,
      experimentally and in patients? Do flow-metabolism coupling mechanisms adjust CBF
      to optimize tissue oxygenation when capillary dysfunction impairs oxygen
      extraction downstream? Cardiovascular risk factors such as age, hypertension,
      diabetes, hypercholesterolemia, and smoking increase the risk of both stroke and
      dementia. The capillary dysfunction phenomenon therefore forces us to consider
      whether changes in capillary morphology or blood rheology may play a role in the
      etiology of some stroke subtypes and in Alzheimer's disease. Here, we discuss
      whether certain disease characteristics suggest capillary dysfunction rather than
      primary flow-limiting vascular pathology and how capillary dysfunction may be
      imaged and managed.

PMID- 25956995
TI  - The effects of sodium hypochlorite and chlorhexidine irrigants on the
      antibacterial activities of alkaline media against Enterococcus faecalis.
AB  - OBJECTIVE: Sodium hypochlorite (NaOCl), chlorhexidine (CHX) and calcium hydroxide
      are common intracanal medicaments. The present study aimed to evaluate the
      effects of NaOCl and CHX on the antibacterial activities of alkaline media
      against Enterococcus faecalis. DESIGNS: The survival rates of planktonic and
      biofilm E. faecalis were evaluated by plate counts after 1 min of pretreatment
      with NaOCl and CHX, and time-kill assays were then used to assess subsequent pH
      alkaline challenges. Dead and living cells in the E. faecalis biofilm were
      assessed with SYTO 9 and PI staining in combination with confocal laser scanning
      microscopy following exposure to NaOCl or CHX and subsequent alkaline challenges
      by common root canal irrigation and dressing procedures. RESULTS: One minute of
      pretreatment with 2% CHX, 0.2% CHX, or 5.25% NaOCl in combination with a
      subsequent alkaline challenge significantly decreased planktonic E. faecalis
      survival rates, but pretreatment with 1% NaOCl did not. The E. faecalis biofilm
      survival rates were reduced in the subsequent alkaline challenge following CHX
      pretreatment but gradually increased following NaOCl pretreatment. Similarly,
      CLSM analysis revealed that the greatest proportions of dead E. faecalis cells in
      the biofilms were presented in the CHX and alkaline treatment group. CONCLUSION:
      CHX might be more effective in improving the antibacterial activities of alkaline
      root canal medicaments against E. faecalis than NaOCl during routine root canal
      therapy procedures.

PMID- 25956996
TI  - Assessment of the current Canadian rhinology workforce.
AB  - BACKGROUND: The Canadian Rhinologic workforce and future needs are not well
      defined. The objective of this study was to define the current demographics and
      practice patterns of the Canadian Rhinologic workforce. Outcomes from this study
      can be used to perform rhinologic workforce needs assessments. METHODS: A
      national survey was administered to all Canadian otolaryngologists who were
      identified to have a clinical practice composed of >50% rhinology. RESULTS: 42
      surgeons participated in the survey (65% response rate). The mean age was 46 (SD
      10.1) years and the average age of planned retirement was 66 (SD 4.0). Eighty
      three percent of respondents had completed a rhinology fellowship and 17%
      practiced exclusively rhinology. Thirty three percent hold advanced degrees.
      Forty two percent of surgeons felt their access to operative time was
      insufficient. Six percent of surgeons reported not having access to image guided
      surgery. Fourteen percent felt that there were too many practicing rhinologists
      in Canada while 17% believed there were too few practicing rhinologists.
      Seventeen percent have advised their residents to pursue other fields due to a
      perceived lack of future jobs. Overall, 66% of respondents were satisfied with
      their income, and 83% were satisfied with their careers. CONCLUSIONS: This study
      has demonstrated that there is a perceived mismatch between the current supply of
      Rhinology labor and the capacity to treat patients in a timely manner. Outcomes
      from this study will begin to improve Rhinologic workforce planning in Canada and
      reduce the gap between patient demand and access to high quality care.

PMID- 25956997
TI  - Synthesis and evaluation of 4-[18F]fluoropropoxy-3-iodobenzylguanidine
      ([18F]FPOIBG): A novel 18F-labeled analogue of MIBG.
AB  - INTRODUCTION: Radioiodinated meta-iodobenzylguanidine (MIBG), a norepinephrine
      transporter (NET) substrate, has been extensively used as an imaging agent to
      study the pathophysiology of the heart and for the diagnosis and treatment of
      neuroendocrine tumors. The goal of this study was to develop an (18)F-labeled
      analogue of MIBG that like MIBG itself could be synthesized in a single
      radiochemical step. Towards this end, we designed 4-fluoropropoxy-3
      iodobenzylguanidine (FPOIBG). METHODS: Standards of FPOIBG and 4-fluoropropoxy-3
      bromobenzylguanidine (FPOBBG) as well as their tosylate precursors for labeling
      with (18)F, and a tin precursor for the preparation of radioiodinated FPOIBG were
      synthesized. Radiolabeled derivatives were synthesized by nucleophilic
      substitution and electrophilic iododestannylation from the corresponding
      precursors. Labeled compounds were evaluated for NET transporter recognition in
      in vitro assays using three NET-expressing cell lines and in biodistribution
      experiments in normal mice, with all studies performed in a paired-label format.
      Competitive inhibition of [(125)I]MIBG uptake by unlabeled benzylguanidine
      compounds was performed in UVW-NAT cell line to determine IC50 values. RESULTS:
      [(18)F]FPOIBG was synthesized from the corresponding tosylate precursor in 5.2 +/
      0.5% (n = 6) overall radiochemical yields starting with aqueous fluoride in
      about 105 min. In a paired-label in vitro assay, the uptake of [(18)F]FPOIBG at
      2h was 10.2 +/- 1.5%, 39.6 +/- 13.4%, and 13.3 +/- 2.5%, in NET-expressing SK-N
      SH, UVW-NAT, and SK-N-BE(2c) cells, respectively, while these values for
      [(125)I]MIBG were 57.3 +/- 8.1%, 82.7 +/- 8.9%, and 66.3 +/- 3.6%. The
      specificity of uptake of both tracers was demonstrated by blocking with
      desipramine. The (125)I-labeled congener of FPOIBG gave similar results. On the
      other hand, [(18)F]FPOBBG, a compound recently reported in the literature,
      demonstrated much higher uptake, albeit less than that of co-incubated
      [(125)I]MIBG. IC50 values for FPOIBG were higher than those obtained for MIBG and
      FPOBBG. Unlike the case with [(18)F]FPOBBG, the heart uptake [(18)F]FPOIBG in
      normal mice was significantly lower than that of MIBG. CONCLUSION: Although
      [(18)F]FPOIBG does not appear to warrant further consideration as an (18)F
      labeled MIBG analogue, analogues wherein the iodine in it is replaced with a
      chlorine, fluorine or hydrogen might be worth pursuing. ADVANCES IN KNOWLEDGE AND
      IMPLICATIONS FOR PATIENT CARE: An (18)F-labeled analogue of the well-known
      radiopharmaceutical MIBG could have significant impact, potentially improving
      imaging of NET related disease in cardiology and in the imaging of neuroendocrine
      tumors. Although (18)F-labeled analogues of MIBG have been reported including
      LMI1195, we undertook this work hypothesizing that based on its greater
      structural similarity to MIBG, FPOIBG might be a better analogue than LMI1195.

PMID- 25956999
TI  - Full-field ERG in diabetic retinopathy: a screening tool?

PMID- 25956998
TI  - Vascular endothelial growth factor levels in tears of patients with retinal vein
      occlusion.
AB  - PURPOSE: We measured vascular endothelial growth factor (VEGF) levels in tear
      fluid and serum in patients with retinal vein occlusion (RVO). PATIENTS AND
      METHODS: Eight patients with RVO due to secondary macular oedema were examined.
      VEGF levels were measured by enzyme-linked immunosorbent assay. All patients had
      a full ophthalmic examination (visual acuity, slit lamp biomicroscopy, perimetry,
      and fluorescein angiography). Central retinal thickness (CRT) was examined using
      optical coherence tomography (OCT). Tear and serum samples were collected and
      examinations were performed at diagnosis and 1 and 4 weeks later. RESULTS: VEGF
      levels in the tears of RVO eyes were significantly higher than in fellow eyes at
      diagnosis and after both 1 and 4 weeks (paired t test, p1 = 0.01, p2 = 0.02, p3 =
      0.006). We found a weak but significant positive correlation between VEGF levels
      in tear fluid and serum of patients with RVO (r = 0.21), while this correlation
      tended to be stronger between the fellow eyes and serum levels (r = 0.33).
      CONCLUSION: To the best of our knowledge, we are the first to report an increased
      level of VEGF in the tear fluid of patients with RVO. Alterations of VEGF levels
      in tears may be useful for determining stages of RVO. This non-invasive and
      objective method may also be helpful for estimating the severity of macular
      oedema and efficacy of treatment.

PMID- 25957000
TI  - Retinal nerve fiber layer structure abnormalities in patients with Neuro-Behcet's
      disease.
AB  - PURPOSE: Our aim was the evaluation of retinal nerve fiber layer (RNFL) and
      central macular thickness (CMT) in patients with Neuro-Behcet's disease (NBD) and
      to compare the results with healthy control subjects. METHODS: We recruited 50
      eyes of 25 patients with NBD and 42 eyes of 21 age-matched healthy control
      subjects. Patients and control subjects underwent a thorough ophthalmic
      examination, including retinal nerve fiber layer and macular thickness
      measurements by optical coherence tomography. RESULTS: No significant difference
      was found between groups for age, sex, intra-ocular pressure and central corneal
      thickness measurements. The average RNFL in patients with NBD was significantly
      lower than that of healthy controls (86.92 +/- 18.36 MUm vs. 99.74 +/- 8.73 MUm;
      p = 0.00). There was significant thinning of the RNFL in three of four quadrants
      of the peripapillary area, superior (107.22 +/- 30.91 MUm vs. 125.57 +/- 20.97
      MUm; p = 0.00), inferior (110.36 +/- 25.57 MUm vs. 132.19 +/- 12.71 MUm; p =
      0.00) and nasal (68.84 +/- 18.47 MUm vs. 74.98 +/- 11.42 MUm; p = 0.05), in
      patients with NBD. Average CMT was significantly lower in NBD patients than in
      control subjects (244.06 +/- 26.25 MUm vs. 261.69 +/- 25.71 MUm; p = 0.00).
      CONCLUSIONS: There are significant differences in average RNFL and CMT between
      the two groups. RNFL and CMT thicknesses are reduced in patients with NBD
      compared with the healthy controls.

PMID- 25957001
TI  - Mean platelet volume in retinopathy of prematurity.

PMID- 25957002
TI  - Activation of the G protein-coupled estrogen receptor, but not estrogen receptor
      alpha or beta, rapidly enhances social learning.
AB  - Social learning is a highly adaptive process by which an animal acquires
      information from a conspecific. While estrogens are known to modulate learning
      and memory, much of this research focuses on individual learning. Estrogens have
      been shown to enhance social learning on a long-term time scale, likely via
      genomic mechanisms. Estrogens have also been shown to affect individual learning
      on a rapid time scale through cell-signaling cascades, rather than via genomic
      effects, suggesting they may also rapidly influence social learning. We therefore
      investigated the effects of 17beta-estradiol and involvement of the estrogen
      receptors (ERs) using the ERalpha agonist propyl pyrazole triol, the ERbeta
      agonist diarylpropionitrile, and the G protein-coupled ER 1 (GPER1) agonist G1 on
      the social transmission of food preferences (STFP) task, within a time scale that
      focused on the rapid effects of estrogens. General ER activation with 17beta
      estradiol resulted in a modest facilitation of social learning, with mice showing
      a preference up to 30min of testing. Specific activation of the GPER1 also
      rapidly enhanced social learning, with mice showing a socially learned preference
      up to 2h of testing. ERalpha activation instead shortened the expression of a
      socially learned food preference, while ERbeta activation had little to no
      effects. Thus, rapid estrogenic modulation of social learning in the STFP may be
      the outcome of competing action at the three main receptors. Hence, estrogens'
      rapid effects on social learning likely depend on the specific ERs present in
      brain regions recruited during social learning. 

PMID- 25957003
TI  - Randomized trials of endoscopic therapy and transjugular intrahepatic
      portosystemic shunt versus portacaval shunt for emergency and elective treatment
      of bleeding gastric varices in cirrhosis.
AB  - IMPORTANCE: Bleeding esophageal varices has been studied extensively, but
      bleeding gastric varices (BGV) has received much less investigation. However, BGV
      has been reported in <= 30% of patients with acute variceal bleeding. In our
      studies of 1,836 bleeding cirrhotics, 12.7% were bleeding from gastric varices.
      BGV mortality rate of 45-55% has been reported. The BGV literature has mainly
      involved retrospective case reports, often with short-term follow-up. OBJECTIVE:
      We sought to describe the results of a prospective, randomized, controlled trial
      (RCT) in unselected, consecutive patients with BGV comparing endoscopic therapy
      (ET) with portacaval shunt (PCS; n = 518), and later comparing emergency
      transjugular intrahepatic portosystemic shunt (TIPS) with emergency portacaval
      shunt (EPCS; n = 70). DESIGN, SETTING, AND PARTICIPANTS: Initially, our RCT
      involved 518 patients with BGV comparing ET with direct PCS regarding control of
      bleeding, mortality rate, and disability. When entry of patients ended, the RCT
      was expanded to compare emergency TIPS with EPCS (n = 70). This RCT of BGV was
      separate from our other RCTs of bleeding esophageal varices. INTERVENTIONS:
      Initially, ET was compared with PCS. In the second part of our RCT, emergency
      TIPS was compared with emergency PCS (EPCS). MAIN OUTCOME MEASURES: Outcomes were
      survival, control of bleeding, portal-systemic encephalopathy (PSE), quality of
      life, and direct costs of care. In the RCT of ET versus PCS, 28 and 30%,
      respectively, were in Child class C. In the expanded RCT of TIPS versus EPCS, 40
      and 41%, respectively, were in Child class C. Permanent control of BGV was
      achieved in 97-100% of patients treated by emergency or elective PCS, compared
      with 27-29% by ET. TIPS was even less effective, achieving long-term control of
      BGV in only 6%. Survival rates after PCS were greater at all time intervals and
      in all Child classes (P < .001). Repeated episodes of PSE occurred in 50% of TIPS
      patients, 16-17% treated by ET, and 8-11% treated by PCS. Shunt stenosis or
      occlusion occurred in 67% of TIPS patients, in contrast with 0-2% of PCS
      patients. CONCLUSION: These results support the conclusion that PCS is uniformly
      effective, whereas ET and TIPS are not very effective.

PMID- 25957004
TI  - Penetrating injury to the inferior vena cava.

PMID- 25957005
TI  - Non-diabetic renal disease in diabetic patients: How to identify? When to biopsy?

PMID- 25957006
TI  - Relationship between circadian blood pressure variability and function of islet
      alpha and beta cell in type 2 diabetes with dyssomnia.
AB  - AIMS: To investigate the relationship between circadian blood pressure (BP)
      variability and function of islet alpha and beta cell in type 2 diabetes (T2D)
      with dyssomnia. METHODS: Patients with T2D were divided into dyssomnia group and
      non-dyssomnia group by PSQI. OGTT, insulin and glucagon-releasing test were
      tested, and ambulatory BP was monitored for 24 hours to compare two groups with
      alpha and beta cell, circadian BP variability and fasting and post-meal BP
      variability. The correlation and regression analysis were made between PSQI and
      other indicators. RESULTS: In dyssomnia group, 1 Glucagon, glucagon/insulin ratio
      and AUCG were significantly higher (P < 0.05). 2 Fasting insulin (13.32 +/- 4.54
      mIU/L), AUCI (8.51 +/- 0.54) and HOMA-IR (4.62 +/- 1.11) were high (P < 0.05).
      But ISI (-4.27 +/- 0.77) was low (P < 0.05). 3 Mean 24-hour and nighttime SBP and
      DBP, as well as their standard deviations and coefficients of variation, were all
      higher in the dyssomnia group (P < 0.05). Multiple stepwise regression analysis
      showed that PSQI score was positively related to AUCG, HOMA-IR, nighttime SBP,
      and negatively related to ISI and nocturnal BP fall (P < 0.05). CONCLUSION:
      Dyssomnia may cause abnormal circadian BP variability through various mechanisms.
      Improving dyssomnia can help to better function the islet alpha and beta cell and
      restore normal circadian BP variability.

PMID- 25957007
TI  - Active inference, communication and hermeneutics.
AB  - Hermeneutics refers to interpretation and translation of text (typically ancient
      scriptures) but also applies to verbal and non-verbal communication. In a
      psychological setting it nicely frames the problem of inferring the intended
      content of a communication. In this paper, we offer a solution to the problem of
      neural hermeneutics based upon active inference. In active inference, action
      fulfils predictions about how we will behave (e.g., predicting we will speak).
      Crucially, these predictions can be used to predict both self and others--during
      speaking and listening respectively. Active inference mandates the suppression of
      prediction errors by updating an internal model that generates predictions--both
      at fast timescales (through perceptual inference) and slower timescales (through
      perceptual learning). If two agents adopt the same model, then--in principle-
      they can predict each other and minimise their mutual prediction errors.
      Heuristically, this ensures they are singing from the same hymn sheet. This paper
      builds upon recent work on active inference and communication to illustrate
      perceptual learning using simulated birdsongs. Our focus here is the neural
      hermeneutics implicit in learning, where communication facilitates long-term
      changes in generative models that are trying to predict each other. In other
      words, communication induces perceptual learning and enables others to
      (literally) change our minds and vice versa.

PMID- 25957008
TI  - [Alzheimer's disease].
AB  - Alzheimer's disease is a progressive neurodegenerative disorder with
      characteristic neuropathological changes. It is the most common form of dementia.
      As a definitive diagnosis requires a neuropathological examination, clinical
      criteria have been established for the diagnostics of a probable Alzheimer's
      disease. In addition to the articles in this issue that focus on the imaging of
      dementia, this article provides a brief overview of clinically relevant aspects
      of Alzheimer's disease. 

PMID- 25957009
TI  - [Normal pressure hydrocephalus].
AB  - CLINICAL ISSUE: Normal pressure hydrocephalus (NPH) is a disorder found mainly in
      the elderly (> 60 years) with an increasing prevalence with age and is one of the
      few treatable causes of dementia. If untreated NPH often leads to severe motor,
      psychomotor and irreversible cognitive deficits. The pathogenesis is not yet
      fully understood. Clinical symptoms consist of the (not always complete)
      classical triad of equilibrium and gait disturbances followed later by
      incontinence and dementia. Symptoms often show a gradual progression to
      irreversibility in non-treated patients; therefore, early diagnosis and treatment
      are mandatory. Important differential diagnoses are Parkinson's disease (similar
      gait), Alzheimer's disease and vascular dementia, not least due to the high
      comorbidity of these conditions with NPH. STANDARD RADIOLOGICAL METHODS: The
      standard radiological method for evaluation of NPH is conventional cross
      sectional imaging that typically shows ventriculomegaly (Evans' index > 0.3 and
      cella media index < 4) often combined with the so-called disproportionately
      enlarged subarachnoid space hydrocephalus (DESH) pattern (tight convexity sulci
      and enlarged sylvian fissure). These findings should be differentiated from
      ventriculomegaly in atrophy combined with enlarged convexity sulci. METHODICAL
      INNOVATIONS: Special magnetic resonance imaging (MRI) techniques can be used to
      evaluate cerebrospinal fluid (CSF) flow but are not yet part of the diagnostic
      guidelines. ACHIEVEMENTS/PRACTICAL RECOMMENDATIONS: Combined with cross-sectional
      imaging, well-established clinical and invasive diagnostic tests, such as
      repeated spinal tap or lumbar drainage with re-evaluation of clinical symptoms
      lead to a diagnosis and help with preoperative patient selection for CSF
      diversion. Ventriculoperitoneal CSF shunting has proven to be safe and is the
      only known successful therapy for NPH.

PMID- 25957010
TI  - Interval versus continuous aerobic exercise training in breast cancer survivors-
      a pilot RCT.
AB  - BACKGROUND: Exercise therapy is being explored in a variety of cancer populations
      to counteract treatment-related deconditioning. Higher intensity interval
      protocols are being prescribed to improve physical function and attenuate
      surrogates of comorbidity in non-cancer populations. The purpose of this study is
      to explore the safety of higher intensity exercise stimuli on cardiorespiratory
      fitness (VO2peak) in breast cancer survivors. METHODS: Postmenopausal breast
      cancer survivors were randomized into three groups: supervised aerobic interval
      training (AIT), supervised continuous moderate exercise training (CMT), and an
      unsupervised control group (CON). For 6 weeks, AIT exercised between 70 and 100%
      VO2peak, while CMT exercised between 60 and 70% VO2peak. Both groups followed a
      matched-work design. RESULTS: Thirty-three participants completed the study (age,
      57.2 (9) years; weight, 67.6 (12) kg) with no adverse advents. Between-group
      baseline values were non-significant. VO2peak at baseline (25.3 (5.4) mL.kg(
      1).min(-1)) was below population norms. Compared to CON, cardiorespiratory
      fitness improved in AIT and CMT by 12% (P < 0.001) with no significant difference
      between exercise groups. AIT had a greater influence on lower extremity strength
      (P = 0.026) and body weight (P = 0.031). CONCLUSION: This pilot study provides
      evidence that similar to CMT, AIT can safely increase VO2peak in a small group of
      breast cancer survivors. Further exploration of the benefits of implementing
      higher intensity training protocols is warranted.

PMID- 25957011
TI  - Feasibility of a quality improvement strategy integrating psychosocial care into
      28 medical cancer centers (HuCare project).
AB  - PURPOSE: This study examines the development and feasibility of a quality
      improvement strategy for the translation of evidence-based psychosocial care into
      clinical practice. METHODS: The project involved all staff (oncologists,
      psychologists, and nurses) of the participating centers. Recommendations
      concerned: improvement of clinician communication skills; use of a patient
      question prompt list; assignment of a specialist nurse to each patient; screening
      for psychological distress and social needs; opportunity to attend a Point of
      Information and Support. The implementation strategy hinged on context analysis
      and problem solving. Four to six visits were held in each center by the project
      team to assist staff in identifying obstacles, finding solutions, and
      strengthening motivation. The primary variable was the adherence percentage to
      the recommendations (proportion of subjects receiving each intervention). The
      number of centers that failed to reach the objective was also reported (adherence
      percentage <75%). RESULTS: Twenty-seven of twenty-eight centers completed the
      study. Lack of resources was the most commonly perceived barrier
      preimplementation. Five-hundred-forty-five clinicians were actively involved in
      the project and completed training. The adherence percentage for each
      recommendation was greater than 85% except for the question prompt list (78%; 95%
      CI, 73-83%), where seven centers did not reach the objective. CONCLUSIONS: Our
      findings demonstrate that evidence-based interventions to improve the
      psychosocial care of people with cancer can be implemented in a diverse range of
      oncology wards. This requires the involvement and motivation of the entire staff
      of the ward, support by an expert team, and promotion by policymakers.

PMID- 25957012
TI  - Psychosocial factors associated with adherence for self-management behaviors in
      women with breast cancer-related lymphedema.
AB  - PURPOSE: Cognitive and affective psychosocial factors have been found to underlie
      adherence to preventive behaviors in women at risk of developing lymphedema
      following treatment for breast cancer. The aim of this study was to determine if
      these factors are associated with adherence to self-management behaviors for
      women diagnosed with breast cancer-related lymphedema (BCRL). METHODS: Women with
      BCRL were recruited through a community-based breast cancer organization and
      three Australian lymphedema treatment clinics. Participants completed an online
      questionnaire assessing demographics, medical history, adherence to self
      management behaviors, psychosocial variables (personal control, treatment
      control, consequences, distress, and self-regulation of affect), and knowledge
      about lymphedema self-management. RESULTS: A total of 166 women participated in
      the study. Participants reported adhering to a mean of five out of seven
      behaviors, with 19.5% of participants adhering to all seven behaviors. Adherence
      to individual behaviors ranged from 65% (self-lymphatic drainage) to 98.2% (skin
      care). Greater knowledge about lymphedema was significantly correlated with
      higher adherence. Hierarchical multiple linear regression analysis indicated that
      only medical history factors (time since diagnosis and having undergone hormone
      replacement therapy) predicted a significant amount of the variance in adherence.
      CONCLUSION: These findings highlight the importance of patient knowledge for
      optimal adherence to a self-management regimen. In addition, medical history
      factors may identify if a patient is at risk of nonadherence. The lack of
      association of adherence with other psychosocial factors considered in this study
      indicates that factors underlying adherence in affected women differ considerably
      from those factors prompting preventive behavior adherence in the at-risk
      population.

PMID- 25957013
TI  - Motivation and preferences of exercise programmes in patients with inoperable
      metastatic lung cancer: a need assessment.
AB  - OBJECTIVES: The aim of this study is to investigate the motivation, ability,
      preferences, and perceived potential facilitating factors/barriers of patients
      with inoperable metastatic lung cancer towards exercise programmes. METHODS: This
      is a cross-sectional study using survey adopting the Theory of Planned Behaviour
      (TPB) to obtain patients' experience recruited through Odette Cancer Centre,
      Sunnybrook Health Sciences Complex. Results were expressed in percentages, P
      value, and Spearman's rho. RESULTS: Sixty patients were recruited from January
      2014 to April 2014. Patients generally had a high level across TPB measures, with
      63% of them indicating that they have the motivation to exercise. Significant
      association in relation to motivation was established on attitudes (importance, P
      = 0.005, rho = 0.326; helpfulness, P = 0.015, rho = 0.348; and easiness, P =
      0.001, rho = 0.375) and subjective norm of close members (P = 0.0069, rho =
      0.348) and healthcare professionals (P = 0.012, rho = 0.328). Being a non-smoker
      (P = 0.042, rho = 0.311), having a past exercise history prior to diagnosis (P =
      0.000, rho = 0.563), and absence of COPD (P = 0.016, rho = -0.312) were also
      shown to have a significant association with motivation to exercise. DISCUSSIONS
      AND CONCLUSIONS: Patients were motivated to participate in an exercise programme
      despite contrary belief; however, they might have limited ability and preferred
      light intensity type of exercise such as walking. Their motivation to exercise
      was driven by different factors when compared to other cancer patient
      populations. Thus, it is important for healthcare professionals to understand the
      factors influencing their motivation and increase their awareness (only 26% of
      patients indicated receiving advice regarding exercise) to better the care
      towards patients with metastatic lung cancer.

PMID- 25957014
TI  - [Introduction to the Thematic Series "Targeted therapies in lung cancers"].

PMID- 25957015
TI  - [The place of extra-corporeal oxygenation in pulmonary diseases].
AB  - Extra-corporeal membrane oxygenation (ECMO) effectively replaces the lung in
      providing oxygenation and carbon dioxide (CO2) removal. For some years, and in
      parallel to the H1N1 influenza pandemic, this technique has gained interest in
      relation to significant technological improvements, leading to new concepts of
      "awake and mobile ECMO" or rehabilitation with ECMO. Finally, the publication of
      randomized controlled trials giving encouraging results in the adult respiratory
      distress syndrome (ARDS) has helped to validate this technique and further
      studies are warranted. This general review aims to outline the definition,
      classification and principles of ECMO and to give some current information about
      the indications and possibilities of the technique to the pulmonologist and
      intensivist. Further possible uses for this technique include extra-corporeal
      removal of CO2 during hypercapnic respiratory failure and assistance during lung
      transplantation from the preoperative to the early postoperative period. 

PMID- 25957016
TI  - Immunohistochemical localization of tenascin-C in rat periodontal ligament with
      reference to alveolar bone remodeling.
AB  - We investigated the immunohistochemical localization of tenascin-C in 8-week-old
      rat periodontal ligaments. Tenascin-C immunoreactivity was detected in zones
      along with cementum and alveolar bone, and more intensely on the resorption
      surface of alveolar bone than on the formation surface. On the resorbing surface,
      tenascin-C immunoreactivity was detected in Howship's lacunae without
      osteoclasts, and in the interfibrous space of the periodontal ligaments,
      indicating that this molecule works as an adhesion molecule between bone and
      fibers of periodontal ligaments. Upon experimental tooth movement by inserting
      elastic bands (Waldo method), the physiological resorption surface of alveolar
      bone under compressive force showed enhanced bone resorption and enhanced
      tenascin-C immunoreactivity. However, on the physiological bone formation surface
      under compressive force, bone resorption was seen only occasionally, and no
      enhanced tenascin-C immunoreactivity was noted. In an experiment involving
      excessive occlusal loading to rat molars, transient bone resorption occurred
      within interradicular septa, but no enhanced tenascin-C immunoreactivity was seen
      in the periodontal ligaments. These results indicate that tenascin-C works
      effectively on the bone resorbing surface of physiological alveolar bone
      remodeling sites, rather than on the non-physiological transient bone resorbing
      surface. Fibronectin immunoreactivity was distributed evenly in the periodontal
      ligaments under experimental conditions. Co-localization of tenascin-C and
      fibronectin immunoreactivity was observed in many regions, but mutually exclusive
      expression patterns were also seen in some regions, indicating that fibronectin
      might not be directly involved in alveolar bone remodeling, but may play a role
      via interaction with tenascin-C. 

PMID- 25957017
TI  - Dissociated large-scale functional connectivity networks of the precuneus in
      medication-naive first-episode depression.
AB  - An imbalance in neural activity within large-scale networks appears to be an
      important pathophysiological aspect of depression. Yet, there is little consensus
      regarding the abnormality within the default mode network (DMN) in major
      depressive disorder (MDD). In the present study, 16 first-episode, medication
      naive patients with MDD and 16 matched healthy controls underwent functional
      magnetic resonance imaging (fMRI) at rest. With the precuneus (a central node of
      the DMN) as a seed region, functional connectivity (FC) was measured across the
      entire brain. The association between the FC of the precuneus and overall symptom
      severity was assessed using the Hamilton Depression Rating Scale. Patients with
      MDD exhibited a more negative relationship between the precuneus and the non-DMN
      regions, including the sensory processing regions (fusiform gyrus, postcentral
      gyrus) and the secondary motor cortex (supplementary motor area and precentral
      gyrus). Moreover, greater severity of depression was associated with greater anti
      correlation between the precuneus and the temporo-parietal junction as well as
      stronger positive connectivity between the precuneus and the dorsomedial
      prefrontal cortex. These results indicate that dissociated large-scale networks
      of the precuneus may contribute to the clinical expression of depression in MDD. 

PMID- 25957018
TI  - Maternal cardiac evaluation during uncomplicated twin pregnancy with emphasis on
      the diastolic function.
AB  - OBJECTIVE: The objective of the study was to evaluate the longitudinal changes in
      maternal systolic and diastolic function in a series of women carrying an
      uncomplicated twin pregnancy. STUDY DESIGN: A series of women carrying a twin
      pregnancy underwent standard M-mode, 2-dimensional color Doppler, and tissue
      Doppler transthoracic echocardiography during the first (11-13 weeks), the second
      (20-23 weeks), the third (28-32 weeks) trimesters, and the postpartum (6 months
      after delivery). RESULTS: From January 2012 to September 2013, 30 women with an
      uncomplicated twin pregnancy were included in this prospective study. All the
      pregnancies were diamniotic including 24 dichorionic and 6 monochorionic sets.
      Overall, 60 live births were observed with a mean gestational age at delivery of
      37 +/- 1 weeks and a mean birthweight of 2532 +/- 313 g. During pregnancy a
      significant worsening of left ventricle systolic function expressed by ejection
      fraction, fractional shortening and S1 longitudinal contractility decrease was
      observed. These findings also persisted at postpartum assessment. Regarding
      diastolic function, our data showed a significant progressive reduction of pulsed
      Doppler E-wave velocity and an increase of A-wave from the first to the third
      trimester. Similar changes were documented for tissue Doppler E1 and A1 peak
      velocities assessed at the level of the mitral and tricuspid annulus. After
      delivery diastolic findings returned to values comparable with those obtained in
      the first trimester. CONCLUSION: In uncomplicated twin gestations, significant
      changes in maternal systolic and diastolic function occur from the first to the
      third trimester. Moreover, although diastolic parameters normalize after
      pregnancy, a relative systolic dysfunction seems to persist after delivery.

PMID- 25957019
TI  - Morbidity associated with cesarean delivery in the United States: is placenta
      accreta an increasingly important contributor?
AB  - OBJECTIVE: The purpose of this study was to examine cesarean delivery morbidity
      and its predictors in the United States. STUDY DESIGN: We used 2000-2011
      Nationwide Inpatient Sample data to identify cesarean deliveries and records with
      12 potential cesarean delivery complications, including placenta accreta. We
      estimated cesarean delivery morbidity rates and rate changes from 2000-2011, and
      fitted Poisson regression models to assess the relative incidence of morbidity
      among repeat vs primary cesarean deliveries and explore its predictors. RESULTS:
      From 2000-2011, 76 in 1000 cesarean deliveries (97 in 1000 primary and 48 in 1000
      repeat cesarean deliveries) were accompanied by >=1 of 12 complications. The
      unadjusted composite cesarean delivery morbidity rate increased by 3.6% only
      among women with a primary cesarean delivery (P < .001); the unadjusted rate of
      placenta accreta increased by 30.8% only among women with a repeat cesarean
      deliveries (P = .025). The adjusted rate of overall composite cesarean delivery
      morbidity decreased by 1% annually from 2000-2011 (P < .001). Compared with women
      with a primary cesarean delivery, those women who underwent a repeat cesarean
      delivery were one-half as likely (incidence rate ratio, 0.50; 95% CI, 0.49-0.50)
      to experience a complication, but 2.13 (95% CI, 1.98-2.29) times more likely to
      have a placenta accreta diagnosis. Both cesarean delivery morbidity and placenta
      accreta were positively associated with age >30 years, non-Hispanic black
      race/ethnicity, the presence of a chronic medical condition, and delivery in
      urban, teaching, or larger hospitals. CONCLUSION: Overall, cesarean delivery
      morbidity declined modestly from 2000-2011, but placenta accreta became an
      increasingly important contributor to repeat cesarean delivery morbidity.
      Clinicians should maintain a high index of suspicion for abnormal placentation
      and make adequate preparations for patients who need cesarean deliveries.

PMID- 25957020
TI  - Cell free DNA testing-interpretation of results using an online calculator.
AB  - All pregnant women, regardless of age, should be offered screening or invasive
      testing for chromosomal abnormalities at <20 weeks' gestation. Noninvasive
      prenatal screening for fetal aneuploidy with the use of cell-free DNA (cfDNA) is
      a screening method that offers high sensitivity and specificity in validation
      studies and has reduced the need for unnecessary invasive procedures.
      Laboratories often advertise and report a test's sensitivity and specificity as a
      means to describe the test's accuracy. The positive predictive value (PPV) of a
      screening test (the proportion of positive results that are truly positive) is a
      function of the prevalence of the condition in a population and often is not
      reported in direct-to-patient advertising. False-positive cfDNA screening tests
      have been reported, and there is evidence that some women are deciding to
      terminate their pregnancy without confirmatory testing. We believe that
      laboratories should disclose the patient-specific PPV of cfDNA screening for
      aneuploidy on result reports. To assist with counseling patients about the
      benefits, risks, and limitations of aneuploidy screening with the use of cfDNA
      and to demonstrate the relationship between an a priori risk and PPV, we
      developed a web-based calculator to estimate the PPV of the 4 commercially
      available cfDNA testing platforms for which data have been published. Estimates
      are made with the use of a patient's age and gestational age-related risk of
      trisomy 21, 18 and 13 or an a priori risk that is based on other findings. This
      web-based calculator is an aid for providers and genetic counselors to illustrate
      the relationship between disease prevalence and a test's PPV. It has enhanced our
      counseling of patients both before they elect noninvasive prenatal screening and
      after they receive a positive result. 

PMID- 25957023
TI  - Customized silicone implant for the correction of acquired and congenital chest
      wall deformities: A valuable option with pectus excavatum.
AB  - BACKGROUND: Surgical remodeling and correction of congenital and acquired chest
      wall deformities (CWD) is undertaken many times for cosmesis. Although reportedly
      minimally invasive, commonly used Nuss procedure for correction of pectus
      excavatum (PE) is not without complications. Nuss procedure is also not suitable
      for complex deformities and Poland syndrome cases. Insertion of custom-made
      silicone implants for the reconstruction of defects has been adopted from adult
      plastic reconstructive surgery as primary repair of CWD or rescue procedure for
      recurrence of PE after recurrence or residual deformity. METHODS: We present our
      experience with CWD reconstruction in children with customized silicone
      prosthesis made from a surgically implantable liquid silicone rubber (NuSil MED
      4805, Ca). RESULTS: Since 2006 we treated 26 patients with CWD: six were children
      (age <17years, median 14.6) with PE. Implants were custom made for each patient's
      chest. The implants were inserted under general anesthesia. Postoperatively all
      patients were fully satisfied with the cosmetic result and subjective patient
      satisfaction remained excellent at follow-up in all the children. Only one child
      developed postoperative complications (seroma). CONCLUSIONS: Customized silicone
      implant for PE in the pediatric age is an alternative therapeutic method, as
      primary or rescue treatment, with equally good cosmetic outcome, fewer
      significant complications, less postoperative pain and a faster recovery.

PMID- 25957022
TI  - Evaluating maternal recovery from labor and delivery: bone and levator ani
      injuries.
AB  - OBJECTIVE: We sought to describe occurrence, recovery, and consequences of
      musculoskeletal (MSK) injuries in women at risk for childbirth-related pelvic
      floor injury at first vaginal birth. STUDY DESIGN: Evaluating Maternal Recovery
      from Labor and Delivery is a longitudinal cohort design study of women recruited
      early postbirth and followed over time. We report here on 68 women who had birth
      related risk factors for levator ani (LA) muscle injury, including long second
      stage, anal tears, and/or older maternal age, and who were evaluated by MSK
      magnetic resonance imaging at both 7 weeks and 8 months' postpartum. We
      categorized magnitude of injury by extent of bone marrow edema, pubic bone
      fracture, LA muscle edema, and LA muscle tear. We also measured the force of LA
      muscle contraction, urethral pressure, pelvic organ prolapse, and incontinence.
      RESULTS: In this higher-risk sample, 66% (39/59) had pubic bone marrow edema, 29%
      (17/59) had subcortical fracture, 90% (53/59) had LA muscle edema, and 41%
      (28/68) had low-grade or greater LA tear 7 weeks' postpartum. The magnitude of LA
      muscle tear did not substantially change by 8 months' postpartum (P = .86), but
      LA muscle edema and bone injuries showed total or near total resolution (P <
      .05). The magnitude of unresolved MSK injuries correlated with magnitude of
      reduced LA muscle force and posterior vaginal wall descent (P < .05) but not with
      urethral pressure, volume of demonstrable stress incontinence, or self-report of
      incontinence severity (P > .05). CONCLUSION: Pubic bone edema and subcortical
      fracture and LA muscle injury are common when studied in women with certain risk
      factors. The bony abnormalities resolve, but levator tear does not, and is
      associated with levator weakness and posterior-vaginal wall descent.

PMID- 25957024
TI  - Enterocystoplasty 30-day outcomes from National Surgical Quality Improvement
      Program Pediatric 2012.
AB  - INTRODUCTION: Enterocystoplasty is an important procedure in the management of
      children with difficult neurogenic bladder. We report on short-term complications
      as captured by National Surgical Quality Improvement Program (NSQIP) Pediatric.
      METHODS: We analyzed NSQIP Pediatric 30-day perioperative data on 114 patients
      who underwent enterocystoplasty in 2012 and compared those with and without
      complications. RESULTS: Neurogenic bladder was the most common diagnosis. The
      proportion of the children who underwent two or more procedures was 71.9%, in
      addition to enterocystoplasty, most commonly appendicovesicostomy. Median length
      of hospital stay was 8 days (mean 9.7 days, range 2 to 46 days). Thirty-day
      complication rate was 33.3%, and the most common complications were urinary tract
      infections (9.6%), wound complications (8.7%), blood transfusions (6.1%), and
      sepsis (3.5%). Reoperation rate and readmission rate were 9.6% and 13.2%,
      respectively. No statistically significant differences in perioperative
      characteristics were found between children with and without postoperative
      complications. Addition of appendicovesicostomy or bladder neck continence
      procedures was not associated with significantly increased complications.
      CONCLUSION: Enterocystoplasty is associated with significant perioperative
      morbidity, and reasonable expectations should be set during preoperative
      counseling.

PMID- 25957021
TI  - Use and attitudes of obstetricians toward 3 high-risk interventions in MFMU
      Network hospitals.
AB  - OBJECTIVE: We sought to evaluate the frequency of, and factors associated with,
      the use of 3 evidence-based interventions: antenatal corticosteroids for fetal
      lung maturity, progesterone for prevention of recurrent preterm birth, and
      magnesium sulfate for fetal neuroprotection. STUDY DESIGN: A self-administered
      survey was conducted from January through May 2011 among obstetricians from 21
      hospitals that included 30 questions regarding their knowledge, attitudes, and
      practice of the 3 evidence-based interventions and the 14-item short version of
      the Team Climate for Innovation survey. Frequency of use of each intervention was
      ascertained from an obstetrical cohort of women between January 2010 and February
      2011. RESULTS: A total of 329 obstetricians (74% response rate) who managed
      16,946 deliveries within the obstetrical cohort participated in the survey. More
      than 90% of obstetricians reported that they incorporated each intervention into
      routine practice. Actual frequency of administration in women eligible for the
      treatments was 93% for corticosteroids, 39% for progesterone, and 71% for
      magnesium sulfate. Provider satisfaction with quality of treatment evidence was
      97% for corticosteroids, 82% for progesterone, and 57% for magnesium sulfate.
      Obstetricians perceived that barriers to treatment were most frequent for
      progesterone (76%), 30% for magnesium sulfate, and 17% for corticosteroids.
      Progesterone use was more frequent among patients whose provider reported the
      quality of the evidence was above average to excellent compared with poor to
      average (42% vs 25%, respectively; P < .001), and they were satisfied with their
      knowledge of the intervention (41% vs 28%; P = .02), and was less common among
      patients whose provider reported barriers to hospital or pharmacy drug delivery
      (31% vs 42%; P = .01). Corticosteroid administration was more common among
      patients who delivered at hospitals with 24 hours a day-7 days a week maternal
      fetal medicine specialist coverage (93% vs 84%; P = .046), CONCLUSION:
      Obstetricians in Maternal-Fetal Medicine Units Network hospitals frequently use
      these evidence-based interventions; however, progesterone use was found to be
      related to their assessment of evidence quality. Neither progesterone nor the
      other interventions were associated with overall climate of innovation within a
      hospital as measured by the Team Climate for Innovation. National Institutes of
      Health Consensus Conference Statements may also have an impact on use; there is
      such a statement for antenatal corticosteroids but not for progesterone for
      preterm prevention or magnesium sulfate for fetal neuroprotection.

PMID- 25957025
TI  - Re-evaluating the need for hospital admission and observation of pediatric
      traumatic brain injury after a normal head CT.
AB  - There is no consensus on the optimal management of pediatric patients with
      suspected trauma brain injury and a normal head CT. This study characterizes the
      clinical outcomes of patients with a normal initial CT scan of the head. A
      retrospective chart review of pediatric blunt trauma patients who underwent head
      CT for closed head injury at two trauma centers was performed. Charts were
      reviewed for demographics, neurologic function, CT findings, and complications.
      631 blunt pediatric trauma patients underwent a head CT. 63% had a negative CT,
      7% had a non-displaced skull fracture, and 31% had an intracranial hemorrhage
      and/or displaced skull fracture. For patients without intracranial injury, the
      mean age was 8 years, mean ISS was 5, and 92% had a GCS of 13-15 on arrival. All
      patients with an initial GCS of 13-15 and no intracranial injury were eventually
      discharged to home with a normal neurologic exam and no patient required
      craniotomy. Not admitting those children with an initial GCS of 13-15, normal CT
      scan, and no other injuries would have saved 1.8 +/- 1.5 hospital days per
      patient. Pediatric patients who have sustained head trauma, have a negative CT
      scan, and present with a GCS 13-15 can safely be discharged home without
      admission.

PMID- 25957026
TI  - Prognostic factors and concomitant anomalies in neonatal gastric perforation.
AB  - OBJECTIVE: Neonatal gastric perforation is a rare and serious issue. This study
      aimed to highlight the vital clinical features and identify prognostic factors in
      such cases. DESIGN, SETTING, PATIENTS, INTERVENTIONS, AND MEASUREMENTS: Medical
      charts from January 1997 through December 2008 were reviewed retrospectively.
      Neonates with a diagnosis of gastric perforation were included. RESULTS: Thirteen
      patients were identified with a male:female ratio of 9:4. Five (38%) were preterm
      infants. The mortality rate was 30% (4/13), and the median age of onset was 3
      days (range: 1-14 days). The most common presenting sign was abdominal
      distension, followed by respiratory distress and vomiting. Except for one patient
      in whom gastric perforation was diagnosed during surgical repair for
      gastroschisis, all patients had pneumoperitoneum on admission; 70% and 46% of
      patients had peritonitis and sepsis, respectively. Concomitant gastrointestinal
      (GI) tract anomalies or disorders included ischemic bowel/necrotizing
      enterocolitis (5 patients), intestinal malrotation (2), duodenal web (1), hiatal
      hernia (1), and gastroschisis (1), which necessitated secondary operations during
      hospitalization in 5 patients. Seven patients had leukopenia on admission, and 9
      developed thrombocytopenia in the following 48 h. All patients who died presented
      with leukopenia on admission and thrombocytopenia in the following 48 h, yielding
      sensitivity and specificity rates of 100% and 67%, respectively. CONCLUSIONS:
      Neonatal gastric perforation is often concomitant with GI anomalies or
      inflammatory/infectious disease. Patients who were outborn and those with
      leucopenia, peritonitis, and thrombocytopenia development within 48 h were at
      risk for poor outcome.

PMID- 25957027
TI  - Long-term follow-up after esophageal replacement in children: 45-Year single
      center experience.
AB  - PURPOSE: We evaluated the results of esophagocoloplasty (ECP) in children by
      performing a 45-year retrospective cohort study in a single center. MATERIALS AND
      METHODS: We collected all of the medical charts of patients who underwent ECP at
      our hospital from January 1969 to January 2014. We reviewed the medical history
      for each patient and then contacted the patients by phone to obtain responses to
      a questionnaire. The questionnaire evaluated the following four areas: overall
      general state, gastrointestinal function, dependence on the Health Sanitary
      System, and their aesthetic satisfaction. RESULTS: We contacted 96 patients, and
      72 completed our questionnaire. There were 45 males and 27 female respondents,
      with a mean age of 34.5 years. The mean Karnofsky performance status index was
      96.4%. There were excellent scores obtained from 55 patients and fairly good
      scores from 16 patients. There was 1 patient with a low score, and there were no
      scores reported below 70%. Most patients (58/72) reported regular bowel habits,
      and no patients required drugs or other measures to facilitate defecation.
      Gastroesophageal reflux was present in 51 patients, and 62.8% have bothersome
      symptoms. Twenty-five patients used pharmacological therapies. Forty-eight
      patients (66.6%) were satisfied with the aesthetic result of surgery (mean score
      in a scale from 0 to 5, is 3). CONCLUSIONS: ECP can be used in children who
      require esophageal substitution. The resulting long-term QoL is acceptable.
      However, the aesthetic outcomes remain a problem.

PMID- 25957028
TI  - MicroRNA-146a-5p attenuates neuropathic pain via suppressing TRAF6 signaling in
      the spinal cord.
AB  - Glia-mediated neuroinflammation plays an important role in the pathogenesis of
      neuropathic pain. Our recent study demonstrated that TNF receptor associated
      factor-6 (TRAF6) is expressed in spinal astrocytes and contributes to the
      maintenance of spinal nerve ligation (SNL)-induced neuropathic pain. MicroRNA
      (miR)-146a is a key regulator of the innate immune response and was shown to
      target TRAF6 and reduce inflammation. In this study, we found that in cultured
      astrocytes, TNF-alpha, IL-1beta, or lipopolysaccharide (LPS) induced rapid TRAF6
      upregulation and delayed miR-146a-5p upregulation. In addition, miR-146a-5p mimic
      blocked LPS-induced TRAF6 upregulation, as well as LPS-induced c-Jun N-terminal
      kinase (JNK) activation and chemokine CCL2 expression in astrocytes. Notably, LPS
      incubation with astrocytes enhanced the DNA binding activity of AP-1 to the
      promoters of mir-146a and ccl2. TRAF6 siRNA or JNK inhibitor SP600125
      significantly reduced LPS-induced miR-146a-5p increase in astrocytes. In vivo,
      intrathecal injection of TNF-alpha or LPS increased spinal TRAF6 expression.
      Pretreatment with miR-146a-5p mimic alleviated TNF-alpha- or LPS-induced
      mechanical allodynia and reduced TRAF6 expression. Finally, SNL induced miR-146a
      5p upregulation in the spinal cord at 10 and 21days. Intrathecal injection of miR
      146a-5p mimic attenuated SNL-induced mechanical allodynia and decreased spinal
      TRAF6 expression. Taken together, the results suggest that (1) miR-146a-5p
      attenuates neuropathic pain partly through inhibition of TRAF6 and its downstream
      JNK/CCL2 signaling, (2) miR-146a-5p is increased by the activation of TRAF6/JNK
      pathway. Hence, miR-146a-5p may be a novel treatment for chronic neuropathic
      pain. 

PMID- 25957029
TI  - Primary Ewing sarcoma of the cavernous sinus.
AB  - INTRODUCTION: Ewing sarcoma (ES) is a part of a larger family of round blue-cell
      tumors that occasionally manifest as osseous or extraosseous lesions adjacent to
      or within the central nervous system (CNS). Although a large body of literature
      exists on ES of bone, data are lacking on tumors with cranial or spinal
      components that affect the CNS. Moreover, primary intracranial ES has been
      uncommonly reported, and its location in the cavernous sinus is extremely rare,
      with only a few cases reported in literature. METHOD: We describe a case of a 15
      year-old boy who presented initially with a seizure along with acute abducens,
      trochlear, and oculomotor nerve pareses. Magnetic resonance imaging (MRI)
      revealed a cavernous sinus mass. Given the rapid growth and aggressive nature of
      the mass, a biopsy of the lesion was performed. Microscopic examination of the
      specimen showed immunohistological features consistent with ES. The patient was
      treated with multi-agent chemotherapy and fractionated radiation therapy. RESULT:
      Clinical assessment 7 months after completion of chemotherapy and 4 months after
      completion of radiotherapy revealed that the patient's ocular motility and
      alignment had improved significantly, and MRI showed almost complete
      disappearance of the tumor. CONCLUSION: This is one of only six cases of
      extraosseous primary intracranial ES of the cavernous sinus reported in
      literature to date. The availability of multi-agent chemotherapy and fractionated
      radiation therapy in this patient resulted in his marked clinical and imaging
      improvement. It remains to be seen if this therapy will result in long-term
      control or cure of the lesion in our patient. In the meantime, increasing
      awareness and identification of children primary intracranial ES will hopefully
      allow a better understanding of the molecular biology of this tumor and the
      development of standardized treatment regimens.

PMID- 25957030
TI  - A new model of detrusor overactivity in conscious rats induced by retinyl acetate
      instillation.
AB  - INTRODUCTION: A credible animal overactive bladder model used in basic research
      is an indispensable harbinger of safe and ethical clinical trials on human
      subjects. Our objective was to develop a new animal model of a hyperactive
      bladder that will be void of inflammatory urothelium lesions and display
      significant sensitivity to muscarinic receptor antagonists. METHODS: To examine
      the influence of 0.75% retinyl acetate solution on cystometric parameters, it was
      infused into the bladder for 5min. Cystometric studies with physiological saline
      were performed in conscious unrestrained rats 3days later. To examine the
      influence of retinyl acetate, acetic acid or cyclophosphamide on morphology of
      urinary bladders, the bladders were subjected to histopathological examination.
      RESULTS: We demonstrated that in rats subject to previous 5-minute bladder
      instillations with retinyl acetate, an increase of basal pressure, threshold
      pressure, micturition voiding pressure, bladder contraction duration, relaxation
      time, detrusor overactivity index, nonvoiding contraction frequency and amplitude
      occurs. On the other hand, a decrease in voided volume, post-void residual,
      volume threshold, voiding efficiency, intercontraction interval, bladder
      compliance and volume threshold to elicit nonvoiding contractions was observed.
      Administration of oxybutynin chloride (0.5mg/kg, i.v.) reversed changes of
      cystometric parameters evoked by retinyl acetate. Contrary to acetic acid and
      cyclophosphamide, bladders subjected to retinyl acetate infusion had no signs of
      bladder inflammation. DISCUSSION: The results obtained indicate that transient
      infusion of 0.75% retinyl acetate can induce detrusor overactivity, which is
      often observed in patients with overactive bladder syndrome (OAB). In addition,
      it was demonstrated that stimulating afferent C-fibres using retinyl acetate did
      not induce evident histopathological inflammatory lesions in the urinary bladder
      wall. It appears that in the future this model can prove useful in gaining more
      knowledge on the pathophysiology of OAB, and contribute to the preparation of
      new, more effective options of OAB pharmacotherapy.

PMID- 25957031
TI  - Comparing mouse and human pluripotent stem cell derived cardiac cells: Both
      systems have advantages for pharmacological and toxicological screening.
AB  - Pluripotent stem cells offer an unparalleled opportunity to investigate cardiac
      physiology, pharmacology, toxicology and pathophysiology. In this paper we
      describe the use of both mouse (Nkx2-5(eGFP/w)) and human (NKX2-5(eGFP/w))
      pluripotent stem cell reporter lines, differentiated toward cardiac lineage, for
      live single cell high acquisition rate calcium imaging. We also assess the
      potential of NKX2-5(eGFP/w) cardiac lineage cells for use toxicological screening
      as well as establish their sensitivity to a shift between low and high oxygen
      environments. Differentiated mouse Nkx2-5(eGFP/w) cells demonstrated a wide range
      of spontaneous oscillation rates that could be reduced by ryanodine (10MUM),
      thapsigargin (1MUM) and ZD7288 (10MUM). In contrast human NKX2-5(eGFP/w) cell
      activity was only reduced by thapsigargin (1MUM). Human cell survival was
      sensitive to the addition of trastuzumab and doxorubicin, while the switch from a
      low to a high oxygen environment affected oscillation frequency. We suggest that
      the human NKX2-5(eGFP/w) cells are less suitable for studies of compounds
      affecting cardiac pacemaker activity than mouse Nkx2-5(eGFP/w) cells, but are
      very suitable for cardiac toxicity studies. 

PMID- 25957032
TI  - Impact of postoperative chemotherapy in patients with locally advanced
      gastroesophageal adenocarcinoma treated with perioperative chemotherapy strategy.
AB  - BACKGROUND: The aim of this study was to determine the clinical impact of
      postoperative chemotherapy (POC) in patients with locally advanced
      gastroesophageal adenocarcinoma and determine the predictors of delivery of
      planned POC. METHODS: All consecutive patients with locally advanced
      gastroesophageal adenocarcinoma treated by perioperative chemotherapy (PCT) at
      our center were selected. Overall survival and disease-free survival were
      compared in patients who did not undergo planned POC (nondelivery of nPOC group)
      and patients who underwent POC (POC group). RESULTS: Among 385 patients who
      underwent esophagectomies or gastrectomies, PCT was performed in 110 patients. Of
      these, 74 (67%) patients underwent POC. Predictors of overall survival included
      postoperative morbidity, pT3-4 stage, R1 resection, and delivery of more than 1
      cycle of POC. Factors predicting POC application included postoperative
      morbidity, esophagectomy, and body mass index. CONCLUSIONS: Two cycles of POC
      were necessary to improve survival in patients with gastroesophageal
      adenocarcinoma.

PMID- 25957033
TI  - Academic Goal Orientation and Cardiovascular Reactivity in a Performance
      Situation.
AB  - The present study investigated whether students' academic goal orientation
      (learning goals, performance goals, work avoidance) and their individual
      competence beliefs (their academic self-concept) can predict motivation-related
      cardiovascular activation patterns in a demanding performance situation. A sample
      of seventy-two undergraduate students rated their academic goal orientation as
      well as their competence beliefs and completed a mental arithmetic task. Heart
      rate (HR), blood pressure, pre-ejection period (PEP) as well as cardiac output
      (CO) and total peripheral resistance were monitored continuously during rest and
      task exposure. Students scoring higher on work avoidance showed smaller increases
      in HR and CO, and a smaller shortening of the PEP. A lower academic self-concept
      was associated with attenuated CO reactivity and a smaller shortening of the PEP.
      Learning and performance goals were unrelated to cardiovascular activity. The
      attenuated cardiac activity observed for work avoidance and competence beliefs
      was interpreted in terms of reduced task engagement resulting from lower success
      importance. 

PMID- 25957034
TI  - Puddles - A trigger for heterogeneous chemical influx into the unsaturated zone.
AB  - Spatial heterogeneity in the chemical concentration of interstitial water in the
      vadose zone was previously observed under apparently homogeneous surface
      conditions on two leveled fields sprinkler irrigated with treated sewage
      effluents on the phreatic Coastal Plain aquifer of Israel. This phenomenon
      greatly hampers the monitoring of groundwater quality. In this study we report on
      the presence of puddles of different size and shape that were sporadically
      observed in these fields. Temporal variability noted in the concentration of
      treated sewage effluents components in the puddles were considered to be related
      to evapotranspiration and degradation. For example: increases in the electrical
      conductivity (up to 1.32 mS/cm), and in the concentrations of chloride (up to 521
      mg/L), dissolved organic carbon (up to 28.4 mg/L), and carbamazepine (up to 780
      ng/L) and decreases in the concentrations of nitrate (up to 20.1mg/L) and
      caffeine (3,396 ng/L). Variable trends in concentration were observed for
      sulfamethoxazole, venlafaxine, 10-hydroxy-10,11-dihydrocarbamazepine and o
      desmethylvenlafaxine. The presence of puddles was not necessarily related to
      areas with high irrigation water input. It is postulated that the continuous
      chemical variability in the puddles, whose location and size are also variable,
      determine a heterogeneous influx of solutes into the soil and subsequently into
      the vadose zone.

PMID- 25957035
TI  - Evolution of water chemistry during Marcellus Shale gas development: A case study
      in West Virginia.
AB  - Hydraulic fracturing (HF) has been used with horizontal drilling to extract gas
      and natural gas liquids from source rock such as the Marcellus Shale in the
      Appalachian Basin. Horizontal drilling and HF generates large volumes of waste
      water known as flowback. While inorganic ion chemistry has been well
      characterized, and the general increase in concentration through the flowback is
      widely recognized, the literature contains little information relative to organic
      compounds and radionuclides. This study examined the chemical evolution of liquid
      process and waste streams (including makeup water, HF fluids, and flowback) in
      four Marcellus Shale gas well sites in north central West Virginia.
      Concentrations of organic and inorganic constituents and radioactive isotopes
      were measured to determine changes in waste water chemistry during shale gas
      development. We found that additives used in fracturing fluid may contribute to
      some of the constituents (e.g., Fe) found in flowback, but they appear to play a
      minor role. Time sequence samples collected during flowback indicated increasing
      concentrations of organic, inorganic and radioactive constituents. Nearly all
      constituents were found in much higher concentrations in flowback water than in
      injected HF fluids suggesting that the bulk of constituents originate in the
      Marcellus Shale formation rather than in the formulation of the injected HF
      fluids. Liquid wastes such as flowback and produced water, are largely recycled
      for subsequent fracturing operations. These practices limit environmental
      exposure to flowback. 

PMID- 25957036
TI  - OH radical-initiated oxidation degradation and atmospheric lifetime of N
      ethylperfluorobutyramide in the presence of O2/NOx.
AB  - The OH radical-initiated oxidation degradation of N-ethylperfluorobutyramide
      (EtFBA) in the presence of O2/NOx was investigated theoretically by using density
      functional theory (DFT). All possible pathways involved in the oxidation process
      were presented and discussed. The study shows that the H abstraction from the
      C(2)H(2) group in EtFBA is the most energetically favorable because of the lowest
      barrier and highest exothermicity. Canonical variational transition-state (CVT)
      theory with small curvature tunneling (SCT) contribution was used to predict the
      rate constants over the temperature range of 180-370 K. At 296 K, the calculated
      overall rate constant of EtFBA with OH radicals is 2.50 * 10(-12)cm(3)molecule(
      1)s(-1). The atmospheric lifetime of EtFBA determined by OH radicals is short,
      about 4.6 days at 296K. However, the atmospheric lifetimes of its primary
      oxidation products, C3F7C(O)N(H)C(O)CH3, C3F7C(O)N(H)CH2CHO and C3F7C(O)NH2, are
      much longer, about 30-50 days. It demonstrates the possibility that the
      atmospheric oxidation degradation of polyfluorinated amides (PFAMs) contributes
      to the burden of observed perfluorinated pollutants in the Arctic region. This
      study reveals for the first time that the water molecule plays an important
      catalytic effect on several key elementary steps and promotes the degradation
      potential of EtFBA.

PMID- 25957037
TI  - Physicochemical and sorptive properties of biochars derived from woody and
      herbaceous biomass.
AB  - It is unclear how the properties of biochar control its ability to sorb metals.
      In this work, physicochemical properties of a variety of biochars, made from four
      types of feedstock at three pyrolysis temperatures (300, 450 and 600 degrees C)
      were compared to their ability to sorb arsenic (As) and lead (Pb) in aqueous
      solutions. Experimental results showed that both feedstock types and pyrolysis
      temperature affected biochar's production rate, i.e., ratio of mass of biochar
      and biomass, thermal stability, elemental composition, non-combustible component
      (NCC) content, pH values, surface areas and thus their sorption ability to the
      two metals in aqueous solution. In general, the high temperature biochars had low
      O/C and H/C ratios, were more carbonized with larger surface area, and were more
      concentrated with alkaline cations. In addition, biochars made from woody
      feedstocks had larger surface area, but lower NCC contents than that made from
      grasses under the same conditions. Although all the tested biochars removed both
      As and Pb from aqueous solutions, they showed different sorption abilities
      because of the variations in properties. Statistical analyses suggested that
      feedstock type affected the sorption ability of the biochars to both As and Pb
      significantly (p<0.001). Pyrolysis temperature, however, showed little influence
      on biochar sorption of Pb in aqueous solutions. Statistical analyses also showed
      that electrostatic interaction played an important role in controlling the
      sorption of both As(V) and Pb(II) onto the biochar. Other mechanisms, such as
      precipitation and surface complexation, could also control the sorption of Pb(II)
      onto the biochars. 

PMID- 25957038
TI  - Non-contact mapping-guided ablation of ventricular arrhythmias originating from
      the pulmonary artery.
AB  - AIMS: To identify unique electrophysiological characteristics of pulmonary artery
      (PA) ventricular arrhythmias (VA) and determine long-term clinical outcomes
      following non-contact mapping (NCM)-guided ablation. METHODS AND RESULTS: The NCM
      array was deployed in consecutive patients undergoing clinically indicated
      ablation of outflow tract (OT) VA with left bundle branch block morphology,
      inferior axis and the precordial lead transition zone >= V3. Activation, pace and
      NCM mapping parameters, and electrocardiogram analysis of PA VA patients were
      compared with 50 patients with right ventricular OT (RVOT) or aortic coronary
      cusps (ACC) foci. Of 170 consecutive patients, 20 (12%) patients (8 male, 39.7 +/
      12.8 years old) with PA VA were identified. Electrocardiogram morphologies of PA
      ventricular tachycardia (VT) (located 10.8 +/- 15.1 mm above the PV) were
      indistinguishable from RVOT VT, particularly those arising from the septal RVOT.
      Pulmonary artery VT can be mapped and ablated by targeting the site of earliest
      activation on NCM maps, with success rates of 90% after a single procedure,
      without anti-arrhythmics and mean follow-up of >5 years. Pace-mapping in the PA
      is complicated by frequent inability to capture (P < 0.01). Small far-field
      atrial potentials and smaller ventricular electrograms were more frequently
      recorded at successful sites of ablation in the PA (P < 0.05). CONCLUSION: Non
      contact mapping is a useful technique to map PA VT and ablation at sites of
      earliest activation above the pulmonary valve is associated with excellent long
      term clinical success.

PMID- 25957040
TI  - Preface.

PMID- 25957039
TI  - Prospective randomized comparison between a fixed '2C3L' approach vs. stepwise
      approach for catheter ablation of persistent atrial fibrillation.
AB  - AIMS: This prospective clinical trial was designed to evaluate the efficacy of an
      ablation strategy, namely '2C3L', in the treatment of persistent atrial
      fibrillation (AF); and to compare its efficacy with that of the 'stepwise'
      approach, which has been acknowledged as a promising ablation technique for
      persistent AF. METHODS AND RESULTS: The '2C3L' technique is a fixed ablation
      approach consisting of bilateral circumferential pulmonary vein antrum isolation
      (PVAI) and three linear ablation lesion sets across the mitral isthmus, left
      atrial roof, and cavo-tricuspid isthmus. One hundred and forty-six patients with
      persistent AF were randomized to undergo ablation by using the '2C3L' or the
      'stepwise' technique (n = 73, respectively). The primary endpoint was freedom
      from any atrial tachyarrhythmia off antiarrhythmic drug (AAD) after a single
      procedure at follow-up. Twelve months after a single procedure, there was no
      difference in sinus rhythm (SR) maintenance rate between the two groups (67% for
      '2C3L' vs. 60% for 'stepwise', P = 0.394; 95% confidence interval of between
      group difference -8.7 to 22.4%). The procedure (222 +/- 42 vs. 263 +/- 41 min),
      fluoroscopy (41 +/- 9 vs. 55 +/- 8 min), and radiofrequency (RF) (107 +/- 32 vs.
      128 +/- 38 min) time were significantly shorter in the '2C3L' group (all P <
      0.001). At 25 +/- 5 months after the first procedure, 57.5 and 52.1% of patients
      from the '2C3L' group and the 'stepwise' group were in SR off AAD (P = 0.494),
      respectively. CONCLUSIONS: For catheter ablation of persistent AF, the '2C3L'
      strategy is a fixed approach associated with clinical efficacy similar to that of
      the 'stepwise' approach but with less RF delivery, fewer X-ray exposure, and
      shorter procedural time.

PMID- 25957041
TI  - Characterisation of major histocompatibility complex class I genes at the fetal
      maternal interface of marsupials.
AB  - Major histocompatibility complex class I molecules (MHC-I) are expressed at the
      cell surface and are responsible for the presentation of self and non-self
      antigen repertoires to the immune system. Eutherian mammals express both
      classical and non-classical MHC-I molecules in the placenta, the latter of which
      are thought to modulate the maternal immune response during pregnancy. Marsupials
      last shared a common ancestor with eutherian mammals such as humans and mice over
      160 million years ago. Since, like eutherians, they have an intra-uterine
      development dependent on a placenta, albeit a short-lived and less invasive one,
      they provide an opportunity to investigate the evolution of MHC-I expression at
      the fetal-maternal interface. We have characterised MHC-I mRNA expression in
      reproductive tissues of the tammar wallaby (Macropus eugenii) from the time of
      placental attachment to day 25 of the 26.5 day pregnancy. Putative classical MHC
      I genes were expressed in the choriovitelline placenta, fetus, and gravid
      endometrium throughout the whole of this period. The MHC-I classical sequences
      were phylogenetically most similar to the Maeu-UC (50/100 clones) and Maeu-UA
      genes (7/100 clones). Expression of three non-classical MHC-I genes (Maeu-UD,
      Maeu-UK and Maeu-UM) were also present in placental samples. The results suggest
      that expression of classical and non-classical MHC-I genes in extant marsupial
      and eutherian mammals may have been necessary for the evolution of the ancestral
      therian placenta and survival of the mammalian fetus at the maternal-fetal
      interface.

PMID- 25957042
TI  - Examining the Usability of Touch Screen Gestures for Older and Younger Adults.
AB  - OBJECTIVE: We examined the usability issues associated with four touch screen
      gestures (clicking, dragging, zooming, and rotating) among older and younger
      users. BACKGROUND: It is especially important to accommodate older users'
      characteristics to ensure the accessibility of information and services that are
      important to their quality of life. METHOD: Forty older and 40 younger
      participants completed four experiments, each of which focused on one gesture.
      The effects of age, type of touch screen (surface acoustic wave vs. optical),
      inclination angle (30 degrees , 45 degrees , 60 degrees , and 75 degrees ), and
      user interface factors (clicking: button size and spacing; dragging: dragging
      direction and distance; zooming: design of zooming gesture; rotating: design of
      rotating gesture) on user performance and satisfaction were examined. RESULTS:
      Button sizes that are larger than 15.9 * 9.0 mm led to better performance and
      higher satisfaction. The effect of spacing was significant only when the button
      size was notably small or large. Rightward and downward dragging were preferred
      to leftward and upward dragging, respectively. The younger participants favored
      direct manipulation gestures using multiple fingers, whereas the older
      participants preferred the click-to design. The older participants working with
      large inclination angles of 60 degrees  to 75 degrees  reported a higher level of
      satisfaction than the older participants working with smaller angles. CONCLUSION:
      We proposed a set of design guidelines for touch screen user interfaces and
      discussed implications for the selection of appropriate technology and the
      configuration of the workspace. APPLICATION: The implications are useful for the
      design of large touch screen applications, such as desktop computers, information
      kiosks, and health care support systems.

PMID- 25957043
TI  - Comparing the Effectiveness of Alerts and Dynamically Annotated Visualizations
      (DAVs) in Improving Clinical Decision Making.
AB  - OBJECTIVE: The aim of this study was to compare the effectiveness of two types of
      real-time decision support, an interrupting pop-up alert and a noninterrupting
      dynamically annotated visualization (DAV), in reducing clinically inappropriate
      diagnostic imaging orders. BACKGROUND: Alerts in electronic health record
      software are frequently disregarded due to high false-alarm rates, interruptions,
      and uncertainty about what triggered the alert. In other settings, providing
      visualizations and improving understandability of the guidance has been shown to
      improve overall decision making. METHOD: Using a between-subject design, we
      examined the effect of two forms of decision support, alerts and DAVs, on
      reducing the proportion of inappropriate diagnostic imaging orders for 11
      patients in a simulated environment. Nine attending and 11 resident physicians
      with experience using an electronic health record were randomly assigned to the
      form of decision support. Secondary measures were self-reported
      understandability, algorithm transparency, and clinical relevance. RESULTS: Fewer
      inappropriate diagnostic imaging tests were ordered with DAVs than with alerts
      (18% vs. 34%, p < .001). The DAV was rated higher for all three secondary
      measures (p < .001) for all participants. CONCLUSION: DAVs were more effective
      than alerts in reducing inappropriate imaging orders and were preferred for all
      patient scenarios, especially scenarios where guidance was ambiguous or based on
      inaccurate information. APPLICATION: Creating visualizations that are permanently
      displayed and vary in the strength of their guidance can mitigate the risk of
      system performance degradation due to incomplete or incorrect data. This
      interaction paradigm may be applicable for other settings with high false-alarm
      rates or where there is a need to reduce interruptions during decision making.

PMID- 25957044
TI  - Perioperative Management of Hypertension in Hand Surgery Patients.

PMID- 25957046
TI  - Family and Work Influences on Stress, Anxiety and Depression Among Bisexual
      Latino Men in the New York City Metropolitan Area.
AB  - The empirical exploration of mental health problems among bisexual Latino men is
      scarce. Bisexual men experience stress because of their non-conforming sexuality
      from multiple-sources. In this study we focus on the family and work
      environments. We conducted a mixed-methods study to examine the impacts of these
      social environments among behavioral bisexual Latino men in New York City (N =
      142). Using the Brief Symptom Inventory we measured stress, depression, and
      anxiety, and used specific scales to measure familial and work social
      environmental stress factors. We also measured four cultural factors to assess
      their potential influence on our hypothesized stressors. To test our hypothesis
      we used linear regression with stress, depression and anxiety as the primary
      outcome variables. Our results indicated that bisexual Latino men experienced
      negative mental health outcomes due to pressures in their familial and work
      environments. Stress was the strongest predictor of anxiety and depression among
      the men in the study. After taking stress into account, familial factors were
      stronger predictors of negative mental health outcomes than work factors.
      Cultural factors such as acculturation and length of living in the United States
      were not associated with negative mental health outcomes in our sample. Our
      findings suggest the importance of addressing stress, anxiety and depression
      among behaviorally bisexual men, and suggest that addressing family-based
      stressors is critical for this population. This research should inform future
      studies addressing this underserved population and provide mental health
      providers with a foundation for working with bisexual Latino men. 

PMID- 25957045
TI  - Nativity and Perceived Healthcare Quality.
AB  - Perceptions of healthcare quality are lower among foreign- than US-born
      individuals. The objective of the study was to identify possible explanations for
      this disparity. Data were from 6202 respondents to cycles 1 and 2 of the Health
      Information National Trends Survey 4 conducted 2011-2013, including 5425 US-born
      and 777 foreign-born respondents. Perceived quality of healthcare was lower among
      foreign-born than US-born respondents, accounted for, to some degree (19.5 %), by
      foreign-born respondents experiencing relatively less patient-centered healthcare
      provider communication than US-born respondents. More patient-centered provider
      communication was associated with receiving higher quality healthcare in all
      respondents. Having a regular provider was associated with perceived quality of
      care in foreign-born but not US-born respondents, and the reverse was true for
      frequency of care. Patient centered provider communication and continuity of care
      may be key targets for improving quality of care for foreign-born individuals.

PMID- 25957047
TI  - Reptin physically interacts with p65 and represses NF-kappaB activation.
AB  - Reptin and Pontin belong to the AAA+ ATPase family of DNA helicases. Both
      proteins are present in several chromatin-remodeling machineries and are involved
      in transcriptional regulation, DNA repair, and telomerase activity, but they also
      function independently from each other. Here we report the identification of p65
      as an interacting partner of Reptin. Using reporter gene assays, we show Reptin
      inhibits NF-kappaB transactivation after TNFalpha stimulation. Reptin is mainly
      localized in the cytoplasm and impedes NF-kappaB activation by inhibiting IkappaB
      alpha degradation and restraining p65 nuclear translocation. These results reveal
      a novel mechanism for the control of NF-kappaB pathway by cytoplasmic Reptin. 

PMID- 25957049
TI  - The radiation resistance and cobalt biosorption activity of yeast strains
      isolated from the Lanyu low-level radioactive waste repository in Taiwan.
AB  - The ubiquitous nature of microbes has made them the pioneers in radionuclides
      adsorption and transport. In this study, the radiation resistance and nuclide
      biosorption capacity of microbes isolated from the Lanyu low-level radioactive
      waste (LLRW) repository in Taiwan was assessed, the evaluation of the possibility
      of using the isolated strain as biosorbents for (60)Co and Co (II) from
      contaminated aqueous solution and the potential impact on radionuclides release.
      The microbial content of solidified waste and broken fragments of containers at
      the Lanyu LLRW repository reached 10(5) CFU/g. Two yeast strains, Candida
      guilliermondii (CT1) and Rhodotorula calyptogenae (RT1) were isolated. The
      radiation dose necessary to reduce the microbial count by one log cycle of CT1
      and RT1 was 2.1 and 0.8 kGy, respectively. Both CT1 and RT1 can grow under a
      radiation field with dose rate of 6.8 Gy/h, about 100 times higher than that on
      the surface of the LLRW container in Lanyu repository. CT1 and RT1 had the
      maximum (60)Co biosorption efficiency of 99.7 +/- 0.1% and 98.3 +/- 0.2%,
      respectively in (60)Co aqueous solution (700 Bq/mL), and the (60)Co could stably
      retained for more than 30 days in CT 1. Nearly all of the Co was absorbed and
      reached equilibrium within 1 h by CT1 and RT1 in the 10 MUg/g Co (II) aqueous
      solution. Biosorption efficiency test showed almost all of the Co (II) was
      adsorbed by CT1 in 20 MUg/g Co (II) aqueous solution, the efficiency of
      biosorption by RT1 in 10 MUg/g of Co (II) was lower. The maximum Co (II) sorption
      capacity of CT1 and RT1 was 5324.0 +/- 349.0 MUg/g (dry wt) and 3737.6 +/- 86.5
      MUg/g (dry wt), respectively, in the 20 MUg/g Co (II) aqueous solution.
      Experimental results show that microbial activity was high in the Lanyu LLRW
      repository in Taiwan. Two isolated yeast strains, CT1 and RT1 have high potential
      for use as biosorbents for (60)Co and Co (II) from contaminated aqueous solution,
      on the other hand, but may have the impact on radionuclides release from LLRW
      repository. 

PMID- 25957048
TI  - Achieving high signal-to-noise in cell regulatory systems: Spatial organization
      of multiprotein transmembrane assemblies of FGFR and MET receptors.
AB  - How is information communicated both within and between cells of living systems
      with high signal to noise? We discuss transmembrane signaling models involving
      two receptor tyrosine kinases: the fibroblast growth factor receptor (FGFR) and
      the MET receptor. We suggest that simple dimerization models might occur
      opportunistically giving rise to noise but cooperative clustering of the receptor
      tyrosine kinases observed in these systems is likely to be important for signal
      transduction. We propose that this may be a more general prerequisite for high
      signal to noise in transmembrane receptor signaling. 

PMID- 25957050
TI  - Shewanella mangrovi sp. nov., an acetaldehyde-degrading bacterium isolated from
      mangrove sediment.
AB  - A taxonomic study was carried out on strain YQH10T, which was isolated from
      mangrove sediment collected from Zhangzhou, China during the screening of
      acetaldehyde-degrading bacteria. Cells of strain YQH10T were Gram-stain-negative
      rods and pale brown-pigmented. Growth was observed at salinities from 0 to 11%
      and at temperatures from 4 to 42  degrees C. Phylogenetic analysis based on 16S
      rRNA gene sequences indicated that strain YQH10T is affiliated to the genus
      Shewanella, showing the highest similarity with Shewanella haliotis DW01T (95.7%)
      and other species of the genus Shewanella (91.4-95.6 %). The principal fatty
      acids were iso-C15 : 0 and C17 : 1omega8c. The major respiratory quinone was Q-8.
      The polar lipids comprised phosphatidylethanolamine and phosphatidylglycerol. The
      genomic DNA had a G+C content of 48.3 mol%. Strain YQH10T can completely degrade
      0.02% (w/v) acetaldehyde on 2216E at 28  degrees C within 48 h. Based on these
      phenotypic and genotypic data, strain YQH10T represents a novel species of the
      genus Shewanella, for which the name Shewanella mangrovi sp. nov. is proposed.
      The type strain is YQH10T ( = MCCC 1A00830T = JCM 30121T).

PMID- 25957051
TI  - Ferruginibacter paludis sp. nov., isolated from wetland freshwater, and emended
      descriptions of Ferruginibacter lapsinanis and Ferruginibacter alkalilentus.
AB  - A Gram-staining-negative, aerobic and rod-shaped bacterium, designated HME8881T,
      was isolated from a freshwater wetland located in the Republic of Korea. A
      phylogenetic analysis based on 16S rRNA gene sequences showed that strain
      HME8881T grouped with members of the genus Ferruginibacter. The most closely
      related species were Ferruginibacter lapsinanis HU1-HG42T (95.6%),
      Ferruginibacter alkalilentus HU1-GD23T (95.1%), 'Ferruginibacter profundus' DS48
      5-3 (94.7%) and Ferruginibacter yonginensis HME8442T (93.4%). The major fatty
      acids were iso-C15 : 0, summed feature 3 (comprising C16 : 1omega7c and/or C16 :
      1omega6c), iso-C15 : 1G, C16 : 0 and iso-C17 : 0 3-OH. A polar lipid analysis
      revealed phosphatidylethanolamine, two unidentified aminolipids, three
      unidentified aminophospholipids, two unidentified phospholipids and two
      unidentified lipids. DNA G+C content was 37.7 mol%. These results suggest that
      strain HME8881T represents a novel species of the genus Ferruginibacter, for
      which the name Ferruginibacter paludis sp. nov., is proposed with the type strain
      HME8881T ( = KCTC 42121T = CECT 8366T). In addition, emended descriptions of
      Ferruginibacter lapsinanis and Ferruginibacter alkalilentus are also proposed on
      the basis of new data obtained during this study.

PMID- 25957053
TI  - Marinithermofilum abyssi gen. nov., sp. nov. and Desmospora profundinema sp.
      nov., isolated from a deep-sea sediment, and emended description of the genus
      DesmosporaYassin et al. 2009.
AB  - Two novel filamentous bacteria, strains SCSIO 11157T and SCSIO 11154T, were
      isolated from a deep-sea sediment sample. Strain SCSIO 11157T grew optimally at
      55-60  degrees C, while strain SCSIO 11154T grew optimally at 40  degrees C. Both
      strains produced aerial and substrate mycelia. Phylogenetic analysis of the 16S
      rRNA gene sequences of strains SCSIO 11157T and SCSIO 11154T showed that the
      isolates were affiliated to the family Thermoactinomycetaceae. The two isolates
      contained ll-diaminopimelic acid as the cell-wall diamino acid, and did not have
      diagnostic sugars. The major polar lipids of strain SCSIO 11157T were
      diphosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylethanolamine
      and phosphatidylglycerol, and the major polar lipids of SCSIO 11154T were
      diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. The
      predominant menaquinone of both strains was MK-7. The major cellular fatty acids
      of strain SCSIO 11157T were iso-C15 : 0, C18 : 1omega9c and iso-C17 : 0, and
      strain SCSIO 11154T contained iso-C15 : 0 and iso-C17 : 0 as major fatty acids.
      The DNA G+C contents of strains SCSIO 11157T and SCSIO 11154T were 54.2 and 51.8
      mol %, respectively. On the basis of its phenotypic and phylogenetic properties,
      strain SCSIO 11157T represents a novel species in the new genus, for which we
      propose the name Marinithermofilum abyssi gen. nov., sp. nov. The type strain of
      Marinithermofilum abyssi is SCSIO 11157T ( = CGMCC 1.15179T = NBRC 109939T).
      Strain SCSIO 11154T represents a novel species of the genus Desmospora, for which
      we propose the name Desmospora profundinema sp. nov. The type strain is SCSIO
      11154T ( = DSM 45903T = NBRC 109626T). 

PMID- 25957052
TI  - Rheinheimera aestuari sp. nov., a marine bacterium isolated from coastal
      sediment.
AB  - A Gram-stain-negative, strictly aerobic, non-pigmented, motile bacterium with a
      single polar flagellum, designated H29T, was isolated from coastal sediment of
      Jeju Island, South Korea. Cells were non-spore-forming rods showing catalase- and
      oxidase-positive reactions. Growth of strain H29T was observed at 10-40  degrees
      C (optimum, 20-25  degrees C) and pH 6.0-9.0 (optimum, pH 7.0-8.0), and in the
      presence of 1-4% (w/v) NaCl (optimum, 2-3%). Strain H29T contained C16 : 0, iso
      C15 : 0 3-OH and summed feature 3 (comprising C16 : 1omega7c/C16 : 1omega6c) as
      the major fatty acids and ubiquinone-8 (Q-8) as the sole isoprenoid quinone.
      Phosphatidylethanolamine and phosphatidylglycerol were identified as the major
      polar lipids. The G+C content of the genomic DNA was 46.5 mol%. Phylogenetic
      analyses based on 16S rRNA gene sequences showed that strain H29T formed a
      phyletic lineage with Rheinheimera hassiensis E48T within the genus Rheinheimera
      of the family Chromatiaceae. Strain H29T was most closely related to Rheinheimera
      pacifica KMM 1406T, Rheinheimera muenzenbergensis E49T, Rheinheimera hassiensis
      E48T and Rheinheimera baltica OSBAC1T with 97.8%, 97.6%, 97.4% and 97.2% 16S rRNA
      gene sequence similarities, respectively. However, DNA-DNA hybridization values
      of strain H29T with type strains of these species were lower than 70%. On the
      basis of the phenotypic, chemotaxonomic and molecular properties, strain H29T
      represents a novel species of the genus Rheinheimera, for which the name
      Rheinheimeraaestuarii sp. nov. is proposed. The type strain is H29T ( = KACC
      18251T = JCM 30404T).

PMID- 25957054
TI  - Accelerated Bone Formation in Distracted Alveolar Bone After Injection of
      Recombinant Human Bone Morphogenetic Protein-2.
AB  - BACKGROUND: This study evaluates the effect of recombinant human bone
      morphogenetic protein-2 (rhBMP-2) on the quality and quantity of regenerated bone
      when injected into distracted alveolar bone. METHODS: Sixteen adult beagle dogs
      were assigned to either the control or rhBMP-2 group. After distraction was
      completed, an rhBMP-2 dose of 330 MUg in 0.33 mL was injected slowly into the
      distracted alveolar crest of the mesial, middle, and distal parts of the alveolar
      bone in the experimental group. Histologic and microcomputed tomography analyses
      of regenerated bone were done after 2 and 6 weeks of consolidation. RESULTS:
      After 6 weeks of consolidation, the vertical defect height in the middle of the
      regenerated bone was significantly lower in the rhBMP-2 group (2.2 mm) than in
      the control group (3.4 mm) (P <0.05). Additionally, the width of the regenerated
      bone was significantly greater in the rhBMP-2 group (4.3 mm) than in the control
      group (2.8 mm) (P <0.05). The bone density and volume of regenerated bone in the
      rhBMP-2 group were greater than in the control group after 6 weeks of
      consolidation (P <0.001). CONCLUSION: Injection of rhBMP-2 into regenerated bone
      after a distraction osteogenesis procedure significantly increased bone volume in
      the dentoalveolar distraction site and improved both the width and height of the
      alveolar ridge and increased the bone density.

PMID- 25957055
TI  - Non-schwannomatosis lesions of the internal acoustic meatus-a diagnostic
      challenge and management: a series report of nine cases.
AB  - Vestibular schwannomas (VS) are the most common lesions of cerebellopontine angle
      (CPA) corresponding to 76-91 % of the cases. Usually, these lesions present
      typical CT and MRI findings. Non-schwannomatous tumors restricted to the internal
      auditory meatus (IAM) are rare and their preoperative radiological diagnosis may
      be difficult. This article describes nine surgically treated intrameatal non
      schwannomatous lesions (NSL) and reviews the literature. In the last 16 years, a
      total of 471 patients with diagnosis of VS were operated on in our department.
      Preoperatively, 42 patients had diagnosis of intrameatal schwannomas, but surgery
      revealed in nine cases NSL (3 meningiomas, 3 arachnoiditis/neuritis, 1 cavernoma,
      1 vascular loop, and 1 arachnoid cyst). Most frequent symptoms presented by
      patients with NSL were hearing loss 89 % (8/9) of patients, tinnitus 78 % (7/9),
      and vertigo 33 % (3/9). Almost all lesions (8/9) presented MRI findings of
      isointense signal in T1W with contrast enhancement. The only exception was the
      arachnoid cyst with intracystic bleeding, which was hyperintense in T1W that is
      not enhanced with contrast. This series shows an occurrence of 21.4 % of non
      schwannomatous tumors in 42 cases of lesions restricted to the IAM. Whenever a
      solely intrameatal enhanced tumor is detected, it is necessary to think about
      other diagnostic possibilities rather than VS. Therapeutic management may be
      changed, specially if radiosurgical treatment is considered. 

PMID- 25957057
TI  - Coronary venous interventions: failed strategy or inadequately explored?

PMID- 25957056
TI  - Impact of Intravenous Lysine Acetylsalicylate Versus Oral Aspirin on Prasugrel
      Inhibited Platelets: Results of a Prospective, Randomized, Crossover Study (the
      ECCLIPSE Trial).
AB  - BACKGROUND: Prasugrel and ticagrelor, new P2Y12-adenosine diphosphate receptor
      antagonists, are associated with greater pharmacodynamic inhibition and reduction
      of cardiovascular events compared with clopidogrel in patients with an acute
      coronary syndrome. However, evidence is lacking about the effects of achieving
      faster and stronger cyclooxygenase inhibition with intravenous lysine
      acetylsalicylate (LA) compared with oral aspirin on prasugrel-inhibited
      platelets. METHODS AND RESULTS: This was a prospective, randomized, single
      center, open, 2-period crossover platelet function study conducted in 30 healthy
      volunteers. Subjects were randomly assigned to receive a loading dose of
      intravenous LA 450 mg plus oral prasugrel 60 mg or loading dose of aspirin 300 mg
      plus prasugrel 60 mg orally in a crossover fashion after a 2-week washout period
      between treatments. Platelet function was evaluated at baseline, 30 minutes, 1 h,
      4 h, and 24 h using light transmission aggregometry and vasodilator-stimulated
      phosphoprotein phosphorylation. The primary end point of the study, inhibition of
      platelet aggregation after arachidonic acid 1.5 mmol/L at 30 minutes, was
      significantly higher in subjects treated with LA compared with aspirin: 85.3%
      versus 44.3%, respectively, P=0.003. This differential effect was observed at 1
      hour (P=0.002) and 4 hours (P=0.048), but not at 24 hours. Subjects treated with
      LA presented less variability and faster and greater inhibition of platelet
      aggregation with arachidonic acid compared with aspirin. CONCLUSIONS: The
      administration of intravenous LA resulted in a significant reduction of platelet
      reactivity compared with oral aspirin on prasugrel-inhibited platelets. Loading
      dose of LA achieves an earlier platelet inhibition and with less variability than
      aspirin. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT02243137.

PMID- 25957058
TI  - Resistance training improves capacity to delay neuromuscular fatigue in older
      adults.
AB  - The purpose of this study was to investigate the effects of short term resistance
      exercise on neuromuscular fatigue threshold (PWCFT), strength, functional
      performance, and body composition in older adults. Twenty-three participants
      (71.2 +/- 6.0 yr) were randomly assigned to 6 weeks of resistance exercise (EXE)
      or control (CONT). A submaximal cycle ergometer test, physical working capacity
      at fatigue threshold, was used to determine PWCFT. Strength was assessed with
      predicted leg extension 1-RM and functional performance with time to complete 5
      chair rises (CHAIR) and walk an 8-ft course (WALK). PWCFT, 1-RM and CHAIR
      significantly (p<0.05) improved in the EXE (27%, 24%, 27%) compared with CONT (
      0.1%, 7%, 6%), respectively. The results of this study suggest that short term
      EXE improved strength, functionality and the capacity to delay the onset of
      neuromuscular fatigue in older adults.

PMID- 25957059
TI  - The association of falls and various physical activities in Chinese
      nonagenarians/centenarians.
AB  - Little is known about the relationship between falls and various physical
      activities in the oldest old people. This study was conducted to observe the
      association of fall with various exercise habits and farm work in very old
      people. In this cross-sectional study of a Chinese cohort of men and women aged
      90-108 years, we observed the association of fall with habitual (current and
      former) farm work and exercise in very old people. The population included 805
      unrelated Chinese nonagenarians and centenarians (68.94% of the subjects were
      women, with a mean age of 93.70 years). In the women, the subjects with a
      continuing exercise habit had a significantly lower prevalence of fall than those
      without an exercise habit; the subjects who had never exercised had a
      significantly higher prevalence of fall than those who exercised. In men, there
      was no significant difference in the prevalence of these habits between the
      subjects with and without fall. After adjusting for age, gender, body mass index,
      educational levels, life styles, vision levels and temperament, we found that
      current habitual farm work (OR=1.755 95% CI (1.107, 2.780)) and exercise OR=0.666
      95% CI (0.445, 0.997) had a significant odds ratio for fall; among the females,
      continuing exercise (vs. having never exercised) had a significant odds ratio for
      fall (OR=0.620 95% CI (0.395, 0.973)). Habitual farm work might be positively
      associated with fall; however, habitual exercise might be negatively associated
      with fall in Chinese long-lived old people. 

PMID- 25957060
TI  - Perspectives on the Etiology of Violence in Later Life.
AB  - This article focuses on the development of a conceptual framework for explaining
      the etiology of violence in later life by various groups involved in the field of
      elder abuse. In this study, we explore this through eight focus groups with
      different professionals involved in the field of elder abuse and older persons
      themselves and in interviews with 35 experts in the field. Our findings show that
      dependency, vulnerability, power and control, social isolation, stress, and care
      burden play a central role in their explanations for the occurrence of violence
      in later life. The role of a history of violence in violence in later life is
      equivocal. The complexity and ambiguity of dependency and vulnerability, the
      notion of mutual dependency, and diverse attitudes and expectations toward them
      that arise with the aging process are distinct features of violence in later life
      that were found.

PMID- 25957061
TI  - Altered Eating Behaviors in Female Victims of Intimate Partner Violence.
AB  - Little is known about altered eating behaviors that are associated with the
      experience of intimate partner violence (IPV) victimization. Our aim was to
      explore the experiences and perspectives of IPV victims regarding their eating
      behaviors and their attitudes toward and use of food. We conducted focus groups
      and individual interviews with 25 IPV victims identified at a domestic violence
      agency and asked them about their eating behaviors and how, if at all, these
      behaviors related to their experience of IPV. Qualitative analysis of the
      transcribed encounters identified themes explicating the relationship between
      their eating behaviors and experiences of IPV. All women described altered eating
      behaviors related to IPV that were categorized into several major themes: (a)
      somatization (victims experience significant somatic symptoms as a result of
      abuse); (b) avoiding abuse (victims modify their eating behaviors to avoid
      abuse); (c) coping (victims use food to handle the psychological effects of
      abuse); (d) self-harm (victims use food to hurt themselves as a reaction to the
      abuse); and (e) challenging abusive partners (victims use their eating behaviors
      to retaliate against their abusers). IPV can provoke altered eating behaviors in
      victims that may be harmful, comforting, or a source of strength in their abusive
      relationships. Understanding the complex relationship between IPV and victims'
      altered eating behaviors is important in promoting healthy eating among victims.

PMID- 25957062
TI  - Contested Discourses in Multidisciplinary Sexual Assault Response Teams (SARTs).
AB  - This qualitative study explored how law enforcement officers, forensic nurses,
      and rape crisis advocates who are members of coordinated service delivery models
      such as Sexual Assault Response Teams (SARTs) describe their process of engaging
      with one another and managing their differences in professional orientation,
      statutory obligations, and power. Using semi-structured interviews with 24 SART
      responders including rape crisis center advocates, law enforcement, and medical
      personnel, we examined the ways that SART members discursively construct one
      another's role in the team and how this process points to unresolved tensions
      that can manifest in conflict. The findings in this study indicate that
      interdisciplinary power was negotiated through discursive processes of
      establishing and questioning the relative authority of team members to dictate
      the work of the team, expertise in terms of knowledge and experience working in
      the field of rape response, and the credibility of one another as qualified
      experts who reliably act in victims' and society's best interests. Implications
      of these findings for understanding and preventing the emergence of conflict in
      SARTs are discussed.

PMID- 25957063
TI  - Gender Norms in Portuguese College Students' Judgments in Familial Homicides: Bad
      Men and Mad Women.
AB  - The gender of the offender has been proved to be an important factor in judicial
      sentencing. In this study, we analyze the judgments of College students regarding
      perpetrators of familial homicides to evaluate the presence of these gender norms
      and biases in the larger society. The sample included 303 college students (54.8%
      female) enrolled in several social sciences and engineering courses. Participants
      were asked to read 12 vignettes based on real crimes taken from Portuguese
      newspapers. Half were related to infanticide, and half were related to intimate
      partner homicide. The sex of the offender was orthogonally manipulated to the
      type of crime. The results show that gender had an important impact on sentences,
      with males being more harshly penalized by reasons of perversity and women less
      penalized by reason of mental disorders. In addition, filicide was more heavily
      penalized than was intimate partner homicide. The results also revealed a
      tendency toward a retributive conception of punishment. We discuss how gender
      norms in justice seem to be embedded in society as well as the need for
      intervention against the punitive tendency of this population.

PMID- 25957064
TI  - School Indicators of Violence Experienced and Feeling Unsafe of Dutch LGB Versus
      Non-LGB Secondary Students and Staff, 2006-2010.
AB  - Gender and sexual orientation are expressed in heterosexual, lesbian (L), gay
      (G), bisexual (B), transgender (T), or queer (Q) interests and behavior. Compared
      with heterosexual persons, LGBTQ persons seem to experience more antisocial
      behavior, including negative discrimination and violence. To assess differences
      in LGBTQ-related discrimination in schools, the question for this research is "Do
      the degrees of violence experienced and feeling unsafe of LGBTQ students and
      staff in a school differ from those of non-LGBTQ students and staff in the same
      school?" Secondary analysis was carried out on data from a Dutch national digital
      monitor survey on safety in secondary schools. In 2006, 2008, and 2010,
      participation amounted to 570 schools, 18,300 teaching and support staff, and
      216,000 students. Four indicators were constructed at the school level: two
      Mokken Scale means assessing severity of violence experienced and two Alpha Scale
      means assessing feeling unsafe. Analysis of mean differences showed that LGB
      students experienced more violence and felt less safe than non-LGB students; LGB
      staff felt less safe in school than non-LGB staff. When LGB students experienced
      more violence at school than non-LGB students, LGB students also felt less safe
      than non-LGB students for all 3 years. No such relationships existed for LGB
      staff, or between LGB staff and LGB students. No significant relationships were
      found between the four LGB school indicators and contextual school variables. The
      outcomes and uniqueness of the study are discussed. Recommendations are made to
      improve assessment and promote prosocial behavior of students and staff in
      schools.

PMID- 25957065
TI  - Estimating osteoporotic fracture risk following a wrist fracture: a tale of two
      systems.
AB  - The WHO fracture risk assessment (FRAX) and Canadian Association of Radiologists
      and Osteoporosis Canada (CAROC) tools can both be used to determine an
      individual's 10-year risk of osteoporotic fracture. However, these tools differ
      in their risk calculation. For participants <65 years with a wrist fracture, FRAX
      provides a lower fracture risk estimate than CAROC resulting in fewer decisions
      to initiate therapy. PURPOSE: The purpose of the current report is to compare
      fracture risk prediction rates using the CAROC and the FRAX(r) tools. METHODS:
      Individuals >=50 years with a distal radius fracture resulting from a fall from
      standing height or less were recruited from a single orthopedic clinic.
      Participants underwent a DXA scan of their lumbar spine and hip. Femoral neck
      (FN) bone mineral density (BMD) and fracture risk factors were used to determine
      each participant's 10-year fracture risk using both fracture risk assessment
      tools. Participants were categorized as low (<10 %), moderate (10-20 %), or high
      (>20 %) risk. Stratified by age (<65 years, >65 years), the proportion of
      participants in each category was compared between the tools. RESULTS: Analyses
      included 60 participants (mean age 65.7 +/- 9.6 years). In those <65 years (n =
      26), the proportion of individuals at low, moderate, and high risk differed
      between the FRAX and CAROC tools (p < 0.0001). FRAX categorized 69 % as low
      (CAROC 0 %) and 3 % as high (CAROC 12 %) risk. For individuals >65 years, almost
      all were at least at moderate risk (FRAX 79 %, CAROC 53 %), but fewer were at
      high risk using FRAX (18 vs. 47 %, p < 0.0003). CONCLUSION: For participants <65
      years with a wrist fracture, FRAX provides a lower estimate of 10-year fracture
      risk than CAROC resulting in fewer decisions to initiate therapy. However, almost
      all participants >65 years were at moderate or high risk under both FRAX and
      CAROC and should at least be considered for pharmacotherapy.

PMID- 25957066
TI  - Association and relative importance of multiple obesity measures with bone
      mineral density: the National Health and Nutrition Examination Survey 2005-2006.
AB  - All obesity measures were positively associated with femoral neck bone mineral
      density (BMD), but not with lumbar spine BMD. Hip circumference was the most
      important obesity measure in relation to BMD. PURPOSE: Multiple measures are used
      to quantify obesity; different obesity measures have diverse relationship with
      BMD. Which obesity measure has the most important value in relation to BMD is
      still poorly understood. We examined the association between multiple obesity
      measures and BMD and determined the relative importance (RI, percentage of
      variation) of multiple obesity measures associated with BMD. METHODS: Data from
      5287 men and women aged between 8 and 69 years (mean age = 29 years) in the
      National Health and Nutrition Examination Survey 2005-2006 were analyzed. Body
      mass index (BMI), waist circumference, hip circumference, body fat mass (FM)
      index, total body FM, abdominal FM, and appendicular FM were considered the
      exposures and femoral neck and lumbar spine BMD the outcomes. RESULTS: In the
      multivariable analysis, greater BMI and hip circumference were associated with
      increased BMD at the lumbar spine and femoral neck (all P < 0.001). The remaining
      obesity variables were positively associated with increased femoral neck BMD only
      (all P < 0.001). RI of all obesity measures associated with femoral neck BMD was
      much greater than that associated with lumbar spine BMD. Moreover, hip
      circumference had higher RI (19.8 for femoral neck BMD; 7.0 for lumbar spine BMD)
      than other obesity measures (all RIs <=14.1 for femoral neck BMD; all RIs <=3.5
      for lumbar spine BMD) in relation to BMD. CONCLUSIONS: All obesity measures were
      positively associated with femoral neck BMD, but not with lumbar spine BMD. Hip
      circumference was the most important obesity measure in relation to BMD.

PMID- 25957067
TI  - Theoretical study of microbubble dynamics in sonoporation.
AB  - Sonoporation is a promising technology for promoting the transfer of drug or gene
      into cells using ultrasound-mediated microbubbles that transiently break up the
      cell membrane. In this article, a model is established to analyze the dynamics of
      ultrasound-mediated microbubble near the cell membrane, which may be especially
      useful for understanding the mechanisms of sonoporation. In the model, the
      velocity potential of fluid on the microbubble surface and on the cell membrane
      is obtained by the unsteady Bernoulli equations, and it is solved by using the
      boundary integral equations. By numerically analyzing the model, the typical
      microbubble dynamics near the cell membrane are enumerated, which may be mainly
      governed by mechanical index. The model also established the connections among
      the parameters of ultrasound exposure, microbubble characteristics, and cell
      membrane properties in sonoporation. 

PMID- 25957068
TI  - Nanoprobing the acidification process during intracellular uptake and
      trafficking.
AB  - Many nanoparticular drug delivery approaches rely on a detailed knowledge of the
      acidification process during intracellular trafficking of endocytosed
      nanoparticles (NPs). Therefore we produced a nanoparticular pH sensor composed of
      the fluorescent pH-sensitive dual wavelength dye carboxy seminaphthorhodafluor-1
      (carboxy SNARF-1) coupled to the surface of amino-functionalized polystyrene NPs
      (SNARF-1-NP). By applying a calibration fit function to confocal laser scanning
      microscopy (CLSM) images, local pH values were determined. The acidification and
      ripening process of endo/lysosomal compartments containing nanoparticles was
      followed over time and was found to progress up to 6h to reach an equilibrium pH
      distribution (maximum pH5.2 [+/-0.2]). The SNARF-1-NP localization in
      endo/lysosomal compartments was confirmed by transmission electron microscopy
      (TEM) and quantitative co-localization analysis with fluorescent endolysosomal
      marker Rab-proteins by confocal laser scanning microscopy (CLSM). The herein
      described nanoparticular pH-sensor is a versatile tool to monitor dynamic pH
      processes inside the endolysosomal compartments. FROM THE CLINICAL EDITOR: In
      this interesting article, the authors elegantly designed a nanoparticular pH
      sensor with fluorescence probe with the capability to measure intracellular and
      intravesicular pH changes. The application of this method would enable the
      further understanding of nanoparticle uptake and intracellular physiology.

PMID- 25957069
TI  - Backbone chemical shift assignments for the sensor domain of the Burkholderia
      pseudomallei histidine kinase RisS: "missing" resonances at the dimer interface.
AB  - Using a deuterated sample, all the observable backbone (1)H(N), (15)N, (13)C(a),
      and (13)C' chemical shifts for the dimeric, periplasmic sensor domain of the
      Burkholderia pseudomallei histidine kinase RisS were assigned. Approximately one
      fifth of the amide resonances are "missing" in the (1)H-(15)N HSQC spectrum and
      map primarily onto alpha-helices at the dimer interface observed in a crystal
      structure suggesting this region either undergoes intermediate timescale motion
      (MUs-ms) and/or is heterogeneous. 

PMID- 25957070
TI  - Lessons learned in the analysis of high-dimensional data in vaccinomics.
AB  - The field of vaccinology is increasingly moving toward the generation, analysis,
      and modeling of extremely large and complex high-dimensional datasets. We have
      used data such as these in the development and advancement of the field of
      vaccinomics to enable prediction of vaccine responses and to develop new vaccine
      candidates. However, the application of systems biology to what has been termed
      "big data," or "high-dimensional data," is not without significant challenges
      chief among them a paucity of gold standard analysis and modeling paradigms with
      which to interpret the data. In this article, we relate some of the lessons we
      have learned over the last decade of working with high-dimensional, high
      throughput data as applied to the field of vaccinomics. The value of such
      efforts, however, is ultimately to better understand the immune mechanisms by
      which protective and non-protective responses to vaccines are generated, and to
      use this information to support a personalized vaccinology approach in creating
      better, and safer, vaccines for the public health. 

PMID- 25957071
TI  - Estimates of pertussis vaccine effectiveness in United States air force pediatric
      dependents.
AB  - BACKGROUND: Pertussis vaccination compliance is critical for reduction in the
      prevalence of disease; however, the current acellular pertussis vaccine may not
      provide sufficient protection from infection. This study examined acellular
      pertussis vaccine effectiveness (VE) for Air Force dependents less than 12 years
      of age. METHODS: We conducted a case-control study among Air Force pediatric
      dependents from 2011 to 2013, comparing cases with positive pertussis test
      results to controls who received the same lab tests with a negative result. Our
      study population was categorized by age group and vaccination status based on the
      Centers for Disease Control and Prevention recommended pertussis vaccination
      schedule. VE was calculated with respect to vaccination status and pertussis lab
      results. RESULTS: We compared 27 pertussis laboratory positive cases with 974
      pertussis laboratory negative controls, 2 months to <12 years old. Comparing
      completely vaccinated to non-vaccinated patients, the overall VE was 78.3% (95%
      confidence interval (CI): 48.6, 90.8; p<0.001). VE was highest among those 15
      months to <6 years old: 97.6% (95% CI: 78.5, 99.7; p<0.001). Children 6 to <12
      years old had the lowest VE: 48.5% (95% CI: -74.0, 84.7; p=0.28). Comparing
      partially vaccinated patients to nonvaccinated patients yielded 64.2% (95% CI: 
      7.2, 88.1; p=0.06) overall VE. CONCLUSIONS: Acellular pertussis vaccination was
      effective at preventing laboratory confirmed pertussis among our Air Force
      pediatric dependent population, with highest protection among completely
      vaccinated, young children. Older children received the lowest amount of
      protection. Partial vaccination had near significant protection. Our overall
      calculated pertussis VE corroborates other pertussis VE studies looking at
      similar age groups.

PMID- 25957072
TI  - The photoelectrochemical exploration of multifunctional TiO2 mesocrystals and its
      enzyme-assisted biosensing application.
AB  - Mesocrystals, as the assemblies of crystallographically oriented nanocrystals,
      have single-crystal-like atom structures and scattering features but with much
      higher porosity than single-crystalline materials, making them promising
      substitutes for conventional single crystals in photoelectrochemical application.
      As a proof-of-concept, a series of photoelectrochemical tests were investigated
      to understand the influence of the differences between them on
      photoelectrochemical activity. Expectedly, comparing with TiO2 single crystals,
      TiO2 mesocrystals demonstrated higher photoelectrochemical capability, which
      provides unique new opportunities for materials design in the fields of solar
      energy conversion and catalysis. Therefore, an elegant photoelectrochemical
      biosensing platform was firstly developed by virtue of carbon nanohorns with
      outstanding electrical conductivity support multifunctional TiO2 mesocrystals to
      accelerate the transfer of photogenerated electrons, and then horseradish
      peroxidase was introduced through the immune recognition reaction for enzyme
      assisted in situ generating CdS QDs. The multiplex amplification strategy
      successfully achieved the ultrasensitive detection of alpha-fetoprotein antigen.
      Promisingly, the successful application of multiplex amplification strategy
      affords a rational and practical consideration for the fabrication of new and
      high-performance photoelectrochemical sensing devices. 

PMID- 25957073
TI  - A cationic surfactant-decorated liquid crystal sensing platform for simple and
      sensitive detection of acetylcholinesterase and its inhibitor.
AB  - In this paper, construction of the liquid crystal (LC)-based sensing platform for
      simple and sensitive detection of acetylcholinesterase (AChE) and its inhibitor
      using a cationic surfactant-decorated LC interface was demonstrated. A change of
      the optical images of LCs from bright to dark appearance was observed when the
      cationic surfactant, myristoylcholine chloride (Myr), was transferred onto the
      aqueous/LC interface, due to the formation of a stable surfactant monolayer at
      the interface. A dark-to-bright change of the optical appearance was then
      observed when AChE was transferred onto the Myr-decorated LC interface. The
      sensitivity of this new type of LC-based sensor is 3 orders of magnitude higher
      in the serum albumin solution than that only in the buffer solution. Noteworthy
      is that the AChE LC sensor shows a very high sensitivity for the detection of the
      enzyme inhibitor, which is around 1 fM. The constructed low-cost LC-based sensor
      is quite simple and convenient, showing high promise for label-free detection of
      AChE and its inhibitors.

PMID- 25957074
TI  - A rapid fluorescence "switch-on" assay for glutathione detection by using carbon
      dots-MnO2 nanocomposites.
AB  - Glutathione (GSH) serves many cellular functions and plays crucial roles in human
      pathologies. Simple and sensitive sensors capable of detecting GSH would be
      useful tools to understand the mechanism of diseases. In this work, a rapid
      fluorescence "switch-on" assay was developed to detect trace amount of GSH based
      on carbon dots-MnO2 nanocomposites, which was fabricated through in situ
      synthesis of MnO2 nanosheets in carbon dots colloid solution. Due to the
      formation of carbon dots-MnO2 nanocomposites, fluorescence of carbon dots could
      be quenched efficiently by MnO2 nanosheeets through fluorescence resonance energy
      transfer (FRET). However, the presence of GSH would reduce MnO2 nanosheets to
      Mn(2+) ions and subsequently release carbon dots, which resulted in sufficient
      recovery of fluorescent signal. This proposed assay demonstrated highly
      selectivity toward GSH with a detection limit of 300nM. Moreover, this method has
      also shown sensitive responses to GSH in human serum samples, which indicated its
      great potential to be used in disease diagnosis. As no requirement of any further
      functionalization of these as-prepared nanomaterials, this sensing system shows
      remarkable advantages including very fast and simple, cost-effective as well as
      environmental-friendly, which suggest that this new strategy could serve as an
      efficient tool for analyzing GSH level in biosamples. 

PMID- 25957075
TI  - Ratiometric analyses at critical temperatures can magnify the signal intensity of
      FRET-based sugar sensors with periplasmic binding proteins.
AB  - Fluorescence resonance energy transfer (FRET)-based sensors transduce ligand
      recognition into a change in the fluorophore spectrum, as ligand binding alters
      the distance between and orientation of two fluorescent proteins. Here, we report
      a dramatic increase in the signal intensity of FRET-based sugar sensors with
      bacterial periplasmic binding proteins (PBPs) in the binding moiety, by
      increasing the analysis temperature, usually higher than 50 degrees C. The
      increased signal intensity results from a sudden decrease in background signal at
      critical temperatures, while recovering the maximum FRET ratios in the presence
      of ligands. When tested with a maltose sensor using a maltose-binding protein as
      the binding moiety, the FRET ratio at the critical temperature, 55 degrees C, was
      17-fold higher than at ambient temperatures. Similar effects were observed using
      analogous sensors for allose, arabinose, and glucose, providing highly dynamic
      and quantitative ratio changes at the critical temperatures. The proposed
      mechanism underlying the signal improvement is thermal relaxation of the binding
      proteins at the critical temperature; this hypothesis was supported by the
      results of intrinsic tryptophan fluorescence and circular dichroism experiments.
      In summary, this study shows that the conformational relaxation of proteins under
      specific conditions can be leveraged for highly sensitive and rapid measurements
      of ligands using FRET-based sensors. 

PMID- 25957076
TI  - Inhibition of microbial growth on air cathodes of single chamber microbial fuel
      cells by incorporating enrofloxacin into the catalyst layer.
AB  - The inevitable growth of aerobic bacteria on the surface of air cathodes is an
      important factor reducing the performance stability of air cathode single-chamber
      membrane-free microbial fuel cells (MFCs). Thus searching for effective methods
      to inhibit the cathodic microbial growth is critical for the practical
      application of MFCs. In this study, enrofloxacin (ENR), a broad spectrum
      fluoroquinolone antibiotic, was incorporated into the catalyst layer of activated
      carbon air cathodes (ACACs) to inhibit the cathodic microbial growth. The biomass
      content on ACACs was substantially reduced by 60.2% with ENR treatment after 91
      days of MFCs operation. As a result of the inhibited microbial growth, the oxygen
      reduction catalytic performance of the ENR treated ACACs was much stable compared
      to the fast performance decline of the untreated control. Consequently, a quite
      stable electricity production was obtained for the MFCs with the ENR treated
      ACACs, in contrast with a 22.5% decrease in maximum power density of the MFCs
      with the untreated cathode. ENR treatment of ACACs showed minimal effects on the
      anode performance. These results indicate that incorporating antibiotics into
      ACACs should be a simple and effective strategy to inhibit the microbial growth
      and improve the long-term stability of the performance of air cathode and the
      electricity production of MFCs. 

PMID- 25957077
TI  - Incidence and predictors of attrition from antiretroviral care among adults in a
      rural HIV clinic in Coastal Kenya: a retrospective cohort study.
AB  - BACKGROUND: Scale up of antiretroviral therapy (ART) has led to substantial
      declines in HIV related morbidity and mortality. However, attrition from ART care
      remains a major public health concern and has been identified as one of the key
      reportable indicators in assessing the success of ART programs. This study
      describes the incidence and predictors of attrition among adults initiating ART
      in a rural HIV clinic in Coastal Kenya. METHODS: A retrospective cohort study
      design was used. Adults (>= 15 years) initiated ART between January 2008 and
      December 2010 were followed up for two years. Attrition was defined as
      individuals who were either reported dead or lost to follow up (LFU, >= 180 days
      late since the last clinic visit). Kaplan Meier survival probabilities and
      Weibull baseline hazard regression analyses were used to model the incidence and
      predictors of time to attrition. RESULTS: Of the 928 eligible participants, 308
      (33.2% [95% CI, 30.2 - 36.3]) underwent attrition at an incident rate of 23.1
      (95% CI, 20.6 - 25.8)/100 pyo. Attrition at 6 and 12 months was 18.4% (95% CI,
      16.0 - 21.1) and 23.2% (95% CI, 19.9 - 25.3) respectively. Gender (male vs.
      female, adjusted hazard ratio [95% CI], p-value: 1.5 [1.1 - 2.0], p = 0.014), age
      (15 - 24 vs. >= 45 years, 2.2 [1.3 - 3.7], p = 0.034) and baseline CD4 T-cell
      count (100 - 350 cells/uL vs. < 100 cells/uL, 0.5 [0.3 - 0.7], p = 0.002) were
      independent predictors of time to attrition. CONCLUSIONS: A third of individuals
      initiating ART were either reported dead or LFU during two years of care, with
      more than a half of these occurring within six months of treatment initiation.
      Practical and sustainable biomedical interventions and psychosocial support
      systems are warranted to improve ART retention in this setting.

PMID- 25957078
TI  - Hepatitis C seroprevalence and HIV co-infection in sub-Saharan Africa: a
      systematic review and meta-analysis.
AB  - BACKGROUND: An estimated 150 million people worldwide are infected with hepatitis
      C virus (HCV). HIV co-infection accelerates the progression of HCV and represents
      a major public health challenge. We aimed to determine the epidemiology of HCV
      and the prevalence of HIV co-infection in sub-Saharan Africa. METHODS: We
      searched Medline and Embase (Ovid) from Jan 1, 2002, to Dec 31, 2014, for studies
      containing data for HCV seroprevalence in different population groups in WHO
      defined regions of sub-Saharan Africa. We estimated pooled regional prevalence
      estimates with a DerSimonian-Laird random-effects model. Data were further
      stratified by risk factor and HIV status. FINDINGS: We included 213 studies from
      33 countries in sub-Saharan Africa, comprising 287 separate cohorts with 1 198
      167 individuals. The pooled HCV seroprevalence from all cohorts was 2.98% (95% CI
      2.86-3.10). The pooled HCV seroprevalence was 2.65% (95% CI 2.53-2.78) across all
      185 low-risk cohorts, 3.04% (2.23-3.84) in antenatal clinic groups, 1.99% (1.86
      2.12) in blood donors, but 6.9% (6.1-7.5) in other general population cohorts.
      The pooled seroprevalence of HCV was 11.87% (95% CI 7.05-16.70) across all high
      risk groups and 9.95% (6.79-13.11) in patients with liver disease. 101 cohorts
      included HIV-positive samples tested for HCV (42 648 individuals), with a pooled
      seroprevalence of 5.73% (95% CI 4.90-6.56). INTERPRETATION: We recorded a high
      seroprevalence of HCV across populations of sub-Saharan Africa, including in HIV
      positive adults, with evidence of regional variation in the general population.
      Monitoring of antenatal HCV prevalence might be a helpful indicator of population
      trends in HCV infection; however, larger population surveys are needed to monitor
      these trends. Access to prevention and treatment needs to be improved for both
      monoinfected and co-infected individuals. FUNDING: None.

PMID- 25957079
TI  - Relief and worries about hepatitis C in sub-Saharan Africa.

PMID- 25957080
TI  - Identification of influential events concerning the Antarctic ozone hole over
      southern Brazil and the biological effects induced by UVB and UVA radiation in an
      endemic treefrog species.
AB  - The increased incidence of solar ultraviolet radiation (UV) due to ozone
      depletion has been affecting both terrestrial and aquatic ecosystems and it may
      help to explain the enigmatic decline of amphibian populations in specific
      localities. In this work, influential events concerning the Antarctic ozone hole
      were identified in a dataset containing 35 years of ozone measurements over
      southern Brazil. The effects of environmental doses of UVB and UVA radiation were
      addressed on the morphology and development of Hypsiboas pulchellus tadpole
      (Anura: Hylidae), as well as on the induction of malformation after the
      conclusion of metamorphosis. These analyzes were complemented by the detection of
      micronucleus formation in blood cells. 72 ozone depletion events were identified
      from 1979 to 2013. Surprisingly, their yearly frequency increased three-fold
      during the last 17 years. The results clearly show that H. pulchellus tadpole are
      much more sensitive to UVB than UVA light, which reduces their survival and
      developmental rates. Additionally, the rates of micronucleus formation by UVB
      were considerably higher compared to UVA even after the activation of photolyases
      enzymes by a further photoreactivation treatment. Consequently, a higher
      occurrence of malformation was observed in UVB-irradiated individuals. These
      results demonstrate the severe genotoxic impact of UVB radiation on this treefrog
      species and its importance for further studies aimed to assess the impact of the
      increased levels of solar UVB radiation on declining species of the Hylidae
      family. 

PMID- 25957081
TI  - Effects from a short-term exposure to copper or cadmium in gravid females of the
      livebearer fish (Gambusia affinis).
AB  - We investigated the reproductive effects of a 10-day maternal metal exposure in
      the live-bearing western mosquitofish. We exposed gravid females to 0.15uM copper
      or cadmium and monitored reproduction-related variables over the subsequent 8
      month breeding season. Females gave birth to 1-5 broods, a number not affected by
      the exposure. Their first brood's size was reduced following exposure to either
      metal, while this effect was still evident for the second brood of copper-exposed
      females. Metal-exposed females also had more premature births, abortions, and
      broods containing dead offspring; these last two effects were still evident in
      second broods. The time-till-first-birth was reduced while the time-interval
      between first and second brood was increased in cadmium-exposed females, but not
      in copper-exposed ones. This study demonstrated that short-term metal exposure
      affects a variety of reproductive measures and that effects can still occur in
      broods that developed well after the end of the females' exposure. 

PMID- 25957082
TI  - Assessing temporal and spatial variation in sensitivity of communities of
      periphyton sampled from agroecosystem to, and ability to recover from, atrazine
      exposure.
AB  - Lotic systems in agriculturally intensive watersheds can experience short-term
      pulsed exposures of pesticides as a result of runoff associated with rainfall
      events following field applications. Of special interest are herbicides that
      could potentially impair communities of primary producers, such as those
      associated with periphyton. Therefore, this study examined agroecosystem-derived
      lotic periphyton to assess (1) variation in community sensitivity to, and ability
      to recover from, acute (48h) exposure to the photosystem II (PSII)-inhibiting
      herbicide atrazine across sites and time, and (2) attempt to determine the
      variables (e.g., community structure, hydrology, water quality measures) that
      were predictive for observed differences in sensitivity and recovery. Periphyton
      were sampled from six streams in the Midwestern U.S. on four different dates in
      2012 (April to August). Field-derived periphyton were exposed in the laboratory
      to concentrations of atrazine ranging from 10 to 320MUg/L for 48h, followed by
      untreated media for evaluation of recovery for 48h. Effective quantum yield of
      PSII was measured after 24h and 48h exposure and 24h and 48h after replacement of
      media. Inhibition of PSII EC50 values ranged from 53 to >320ug/L. The majority of
      periphyton samples (16 out of 22) exposed to atrazine up to 320ug/L recovered
      completely by 48h after replacement of media. Percent inhibition of effective
      quantum yield of PSII in periphyton (6 of 22 samples) exposed to 320ug/L atrazine
      that were significantly lower than controls after 48h ranged from 2% to 24%. No
      distinct spatial or temporal trends in sensitivity and recovery potential were
      observed over the course of the study. Conditional inference forest analysis and
      variation partitioning were used to investigate potential associations between
      periphyton sensitivity to and ability to recover from exposure to atrazine.
      Although certain environmental variables (i.e., proximity of high flow/velocity
      events and dissolved solutes) were significantly associated with sensitivity to
      atrazine, recovery was not significantly associated with any variables, which is
      predicted by the rapid reversible binding at PSII. Consistent and rapid recovery
      of effective quantum yield of PSII across sites and sampling dates indicates that
      acute exposure to atrazine is unlikely to adversely affect function of these
      communities in their current state in intensive agroecosystems. 

PMID- 25957083
TI  - Posttraumatic stress disorder and cancer risk: a nationwide cohort study.
AB  - The association between stress and cancer incidence has been studied for more
      than seven decades. Despite plausible biological mechanisms and evidence from
      laboratory studies, findings from clinical research are conflicting. The
      objective of this study was to examine the association between PTSD and various
      cancer outcomes. This nation-wide cohort study included all Danish-born residents
      of Denmark from 1995 to 2011. The exposure was PTSD diagnoses (n = 4131). The
      main outcomes were cancer diagnoses including: (1) all malignant neoplasms; (2)
      hematologic malignancies; (3) immune-related cancers; (4) smoking- and alcohol
      related cancers; (5) cancers at all other sites. Standardized incidence ratios
      (SIR) were calculated. Null associations were found between PTSD and nearly all
      cancer diagnoses examined, both overall [SIR for all cancers = 1.0, 95 %
      confidence interval (CI) = 0.88, 1.2] and in analyses stratified by gender, age,
      substance abuse history and time since PTSD diagnosis. This study is the most
      comprehensive examination to date of PTSD as a predictor of many cancer types.
      Our data show no evidence of an association between PTSD and cancer in this
      nationwide cohort.

PMID- 25957084
TI  - Antibiotic exposure in the first year of life and later treated asthma, a
      population based birth cohort study of 143,000 children.
AB  - Several epidemiological studies reported an association between antibiotic
      consumption in the first year of life and later asthma, but results are
      conflicting and affected by potential biases. We examined this controversial
      issue in a population-based birth cohort. Using administrative data, we
      identified 143,163 children born in 1995-2011 in Friuli-Venezia Giulia (Italy)
      (median follow-up 5.25 years, 927,350 person-years). Antibiotic prescriptions in
      the first year of life and subsequent treated asthma (defined as >=2 anti
      asthmatic drug prescriptions within a 12-month period) were retrieved from drug
      prescription records. We estimated incidence rate ratios (IRR) using Poisson
      regression models, adjusted for perinatal variables and for hospitalizations for
      infections in the first year of life. We identified 34,957 new-onset asthma
      cases. Antibiotic consumption in the first year of life increased the risk of new
      onset asthma [IRR 1.51, 95% confidence interval (CI) 1.48-1.54] with a dose
      response relationship (p-trend <0.001). The risk was highest for asthma
      identified at 13-35 months of life (IRR 2.07, 95% CI 2.00-2.14), but remained
      statistically significant for asthma identified at 36-71 months (IRR 1.17, 95% CI
      1.14-1.21) and at >=72 months (IRR 1.15, 95% CI 1.08-1.22). Antibiotics increased
      the risk of current asthma at >=6 years (IRR 1.35, 95% CI 1.30-1.41) and at >=13
      years of age (IRR 1.19, 95% CI 1.08-1.33). Antibiotic exposure in infancy is
      associated with an increased risk of asthma up to adolescence. The association
      detected at older ages is not explained by reverse causation; however,
      confounding by respiratory infections not leading to hospital admission cannot be
      excluded.

PMID- 25957085
TI  - The carboxy-terminal tail or the intracellular loop 3 is required for beta
      arrestin-dependent internalization of a mammalian type II GnRH receptor.
AB  - The type II GnRH receptor (GnRH-R2) in contrast to mammalian type I GnRH receptor
      (GnRH-R1) has a cytosolic carboxy-terminal tail. We investigated the role of beta
      arrestin 1 in GnRH-R2-mediated signalling and mapped the regions in GnRH-R2
      required for recruitment of beta-arrestin, employing internalization assays. We
      show that GnRH-R2 activation of ERK is dependent on beta-arrestin and protein
      kinase C. Appending the tail of GnRH-R2 to GnRH-R1 enabled GRK- and beta-arrestin
      dependent internalization of the chimaeric receptor. Surprisingly, carboxy
      terminally truncated GnRH-R2 retained beta-arrestin and GRK-dependent
      internalization, suggesting that beta-arrestin interacts with additional elements
      of GnRH-R2. Mutating serine and threonine or basic residues of intracellular loop
      3 did not abolish beta-arrestin 1-dependent internalization but a receptor
      lacking these basic residues and the carboxy-terminus showed no beta-arrestin 1
      dependent internalization. Our results suggest that basic residues at the amino
      terminal end of intracellular loop 3 or the carboxy-terminal tail are required
      for beta-arrestin dependent internalization. 

PMID- 25957087
TI  - 9-Demethoxy-medicarpin promotes peak bone mass achievement and has bone
      conserving effect in ovariectomized mice: Positively regulates osteoblast
      functions and suppresses osteoclastogenesis.
AB  - We report a new bone anabolic and anti-catabolic pterocarpan 9-demethoxy
      medicarpin (DMM) for the management of postmenopausal osteoporosis. DMM promoted
      osteoblast functions via activation of P38MAPK/BMP-2 pathway and suppressed
      osteoclastogenesis in bone marrow cells (BMCs). In calvarial osteoblasts, DMM
      blocked nuclear factor kappaB (NFkappaB) signaling and inhibited the mRNA levels
      of pro-inflammatory cytokines. DMM treatment led to increased OPG
      (osteoprotegrin) and decreased transcript levels of TRAP (tartarate resistant
      acid phosphatase), RANK (receptor activator of NFkappaB) and RANKL (RANK ligand)
      in osteoblast-osteoclast co-cultures. Immature female SD rats administered with
      DMM exhibited increased bone mineral density, bone biomechanical strength, new
      bone formation and cortical bone parameters. Ovx mice administered with DMM led
      to significant restoration of trabecular microarchitecture and had reduced
      formation of osteoclasts and increased formation of osteoprogenitor cells in
      BMCs. DMM exhibited no uterine estrogenicity. Overall, these results demonstrate
      the therapeutic potential of DMM for the management of postmenopausal
      osteoporosis. 

PMID- 25957086
TI  - IGFBP-1 hyperphosphorylation in response to leucine deprivation is mediated by
      the AAR pathway.
AB  - Insulin-like growth factor-1 (IGF-I) is the key regulator of fetal growth. IGF-I
      bioavailability is markedly diminished by IGF binding protein-1 (IGFBP-1)
      phosphorylation. Leucine deprivation strongly induces IGFBP-1
      hyperphosphorylation, and plays an important role in fetal growth restriction
      (FGR). FGR is characterized by decreased amino acid availability, which activates
      the amino acid response (AAR) and inhibits the mechanistic target of rapamycin
      (mTOR) pathway. We investigated the role of AAR and mTOR in mediating IGFBP-1
      secretion and phosphorylation in HepG2 cells in leucine deprivation. mTOR
      inhibition (rapamycin or raptor + rictor siRNA), or activation (DEPTOR siRNA)
      demonstrated a role of mTOR in leucine deprivation-induced IGFBP-1 secretion but
      not phosphorylation. When the AAR was blocked (U0126, or ERK/GCN2 siRNA), both
      IGFBP-1 secretion and hyperphosphorylation (pSer101/pSer119/pSer169) due to
      leucine deprivation were prevented. CK2 inhibition by TBB also attenuated IGFBP-1
      phosphorylation in leucine deprivation. These results suggest that the AAR and
      mTOR independently regulate IGFBP-1 secretion and phosphorylation in response to
      decreased amino acid availability. 

PMID- 25957088
TI  - Co-administration of insulin with a gonadotropin partly improves ovulatory
      responses of estrogen-deficient mice.
AB  - Administration of 17-betaestradiol (E2) with pregnant mare serum gonadotropin
      (PMSG) and human chorionic gonadotropin (hCG) can induce ovulation in estrogen
      deficient (ArKO) mice; nevertheless, ovulatory efficiency and rate are low. In
      this study, effects of insulin on the ovulatory responses were investigated. In
      ArKO ovary, hCG signal was found to be transmitted in an uncoordinated manner
      when phosphorylation levels of signaling molecules are examined. Co
      administration of insulin with hCG improved the transmission of hCG signal as
      well as the ovulatory efficiency in ArKO mice. It also improved the ovulatory
      rate but far below the wild-type rate. Gene expression analysis demonstrated that
      Cyp11a1 and Cyp17a1 mRNAs were significantly induced 4 h after PMSG
      administration in the wild-type ovary, but not in ArKO ovary. Collectively, these
      results suggest that insulin improves ovulatory responses of ArKO mice, but it
      fails to ameliorate follicular dysfunctions caused possibly by an inappropriate
      intraovarian milieu during follicular maturation. 

PMID- 25957089
TI  - Is this the right normalization? A diagnostic tool for ChIP-seq normalization.
AB  - BACKGROUND: Chip-seq experiments are becoming a standard approach for genome-wide
      profiling protein-DNA interactions, such as detecting transcription factor
      binding sites, histone modification marks and RNA Polymerase II occupancy.
      However, when comparing a ChIP sample versus a control sample, such as Input DNA,
      normalization procedures have to be applied in order to remove experimental
      source of biases. Despite the substantial impact that the choice of the
      normalization method can have on the results of a ChIP-seq data analysis, their
      assessment is not fully explored in the literature. In particular, there are no
      diagnostic tools that show whether the applied normalization is indeed
      appropriate for the data being analyzed. RESULTS: In this work we propose a novel
      diagnostic tool to examine the appropriateness of the estimated normalization
      procedure. By plotting the empirical densities of log relative risks in bins of
      equal read count, along with the estimated normalization constant, after
      logarithmic transformation, the researcher is able to assess the appropriateness
      of the estimated normalization constant. We use the diagnostic plot to evaluate
      the appropriateness of the estimates obtained by CisGenome, NCIS and CCAT on
      several real data examples. Moreover, we show the impact that the choice of the
      normalization constant can have on standard tools for peak calling such as MACS
      or SICER. Finally, we propose a novel procedure for controlling the FDR using
      sample swapping. This procedure makes use of the estimated normalization constant
      in order to gain power over the naive choice of constant (used in MACS and
      SICER), which is the ratio of the total number of reads in the ChIP and Input
      samples. CONCLUSIONS: Linear normalization approaches aim to estimate a scale
      factor, r, to adjust for different sequencing depths when comparing ChIP versus
      Input samples. The estimated scaling factor can easily be incorporated in many
      peak caller algorithms to improve the accuracy of the peak identification. The
      diagnostic plot proposed in this paper can be used to assess how adequate
      ChIP/Input normalization constants are, and thus it allows the user to choose the
      most adequate estimate for the analysis.

PMID- 25957090
TI  - Cardiac lipoma in the interventricular septum: a case report.
AB  - Primary cardiac tumors are rare. The cardiac lipoma cases have been sparsely
      reported. We report a case of interventricular septal lipoma complicated with
      mild tricuspid regurgitation in a 65-year-old Chinese male. The patient presented
      with shortness of breath after exertion. His diagnosis was made with
      echocardiogram, cardiac magnetic resonance imaging, cardiac computed tomography
      and post-operative histopathology. The patient underwent tumor resection and
      postoperative recovery was uneventful. He was asymptomatic with no recurrence at
      8-month follow-up. 

PMID- 25957092
TI  - Video-assisted thoracic surgery for pulmonary sequestration.
AB  - Bronchopulmonary sequestration is a rare developmental abnormality. Most cases
      are asymptomatic and found incidentally. The definitive treatment for
      bronchopulmonary sequestration is surgical excision. An 18-year-old man was
      admitted to our clinic with longstanding cough, fever, and dense sputum. Chest
      computed tomography identified cystic bronchiectasis in common areas of the left
      lower lobe, and parenchymal destruction with air-fluid levels. A left lower
      lobectomy was performed via a video-thoracoscopic approach. 

PMID- 25957091
TI  - Supravalvular aortic stenosis after arterial switch operation.
AB  - Supravalvular aortic stenosis as a late complication of transposition of the
      great arteries is very rare, and only a few cases have been reported. We describe
      the case of a 14-year-old girl who developed supravalvular aortic stenosis as a
      late complication of the arterial switch operation for transposition of the great
      arteries. The narrowed ascending aorta was replaced with a graft. The right
      pulmonary artery was transected to approach the ascending aorta which adhered
      severely to the main pulmonary trunk, and we obtained a good operative field. 

PMID- 25957093
TI  - Spontaneous rib fractures.
AB  - BACKGROUND: Other than trauma, rib fracture can occur spontaneously due to a
      severe cough or sneeze. In this study, patients with spontaneous rib fractures
      were analyzed according to age, sex, underlying pathology, treatment, and
      complications. METHODS: Twelve patients who presented between February 2009 and
      February 2011 with spontaneous rib fracture were reviewed retrospectively. The
      patients' data were evaluated according to anamnesis, physical examination, and
      chest radiographs. RESULTS: The ages of the patients ranged from 34 to 77 years
      (mean 55.91 +/- 12.20 years), and 7 (58.4%) were male. All patients had severe
      cough and chest pain. The fractures were most frequently between 4th and 9th
      ribs; multiple rib fractures were detected in 5 (41.7%) patients. Eight (66.7%)
      patients had chronic obstructive pulmonary disease, 2 (16.7%) had bronchial
      asthma, and 2 (16.7%) had osteoporosis. Bone densitometry revealed a high risk of
      bone fracture in all patients. Patients with chronic obstructive pulmonary
      disease or bronchial asthma had been treated with high-dose steroids for over a
      year. CONCLUSIONS: Spontaneous rib fracture due to severe cough may occur in
      patients with osteoporosis, chronic obstructive pulmonary disease, or bronchial
      asthma, receiving long-term steroid therapy. If these patients have severe chest
      pain, chest radiography should be performed to check for bone lesions.

PMID- 25957094
TI  - Antidepressant-like effect of food-derived pyroglutamyl peptides in mice.
AB  - The N-terminal glutamine residue, exposed by enzymatic cleavage of precursor
      proteins, is known to be modified to a pyroglutamyl residue with a cyclic
      structure in not only endogenous but also food-derived peptides. We investigated
      the effects of wheat-derived pyroglutamyl peptides on emotional behaviors.
      Pyroglutamyl leucine (pyroGlu-Leu, pEL) and pyroglutamyl glutaminyl leucine
      (pyroGlu-Gln-Leu, pEQL) exhibited antidepressant-like activity in the tail
      suspension and forced swim tests in mice. pEQL exhibited more potent
      antidepressant-like activity than pEL after i.p. and i.c.v. administration. pEQL
      exhibited antidepressant-like activity at a lower dose than Gln-Gln-Leu,
      suggesting that pyroglutamyl peptide had more potent activity. To examine whether
      pyroglutamyl peptides increased hippocampus neurogenesis, associated with the
      effects of antidepressants, we measured 5-bromo-2'-deoxyuridine (BrdU)
      incorporation. pEL and pEQL increased BrdU-positive cells in the dentate gyrus of
      the hippocampus. Intriguingly, pEL did not increase hippocampal mRNA and protein
      expression of brain-derived neurotrophic factor (BDNF), which is a factor
      associated with both neuropoietic and antidepressive effects. Thus, pyroglutamyl
      peptides may enhance hippocampal neurogenesis via a pathway independent of BDNF.
      We also confirmed that pEL and pEQL were produced in the subtilisin digest of
      major wheat proteins, glutenin and gliadin, after heat treatment. pEL and pEQL
      are the first peptides derived from wheat proteins to be shown to exhibit an
      antidepressant-like activity. 

PMID- 25957095
TI  - Risks and benefits of low molecular-weight heparin and target-specific oral
      anticoagulant use for thromboprophylaxis in medically ill patients.
AB  - Venous thromboembolism is the third most common cardiovascular disease and a
      major cause of inpatient mortality as over 50 % of deep vein thrombosis and
      pulmonary embolism are undetected in medically treated patients. Several agents
      are approved for thromboprophylaxis, including warfarin, unfractionated heparin,
      low molecular-weight heparins, fondaparinux, and target-specific oral
      anticoagulants. The purpose of this literature review is to discuss the increased
      risk of venous thromboembolism in medically ill patients and the literature
      surrounding the efficacy and tolerability of low molecular-weight heparins and
      target-specific oral anticoagulants for this indication. PubMed, MEDLINE,
      EBSCOhost, and clinicaltrials.gov were used as search engines in the literature
      review. Search limits included articles containing human subjects, scholarly
      (peer-reviewed) journals written in English, and publication dates from 2004 to
      2014. Animal studies, non-English articles, and publications dated prior to 2004
      were excluded. Recurrent venous thromboembolism remains an ongoing problem
      affecting thousands of people in the non-surgical population annually. With
      limited data, it is not likely that target-specific oral anticoagulants will soon
      replace low molecular-weight heparins or even be considered an alternative until
      efficacy and tolerability have been established. Until further evidence is
      disclosed, low molecular-weight heparins and fondaparinux (in the absence of
      renal dysfunction and low body weight) should continue to be utilized as first
      line agents for thromboprophylaxis in medically ill patients. The use of apixaban
      and rivaroxaban is discouraged for thromboprophylaxis in medically ill patients. 

PMID- 25957097
TI  - A single-amino-acid mutation in hepatitis C virus NS5A disrupts physical and
      functional interaction with the transcription factor HNF-1alpha.
AB  - Hepatitis C virus (HCV) infection often causes extrahepatic manifestations, such
      as type 2 diabetes. We previously reported that HCV infection induces the
      lysosomal degradation of the transcription factor HNF-1alpha via an interaction
      with viral NS5A, thereby suppressing GLUT2 gene expression. However, the
      molecular mechanism of NS5A-induced degradation of HNF-1alpha is largely unknown.
      We aimed to identify the determinants necessary for the degradation of HNF-1alpha
      induced by NS5A. Coimmunoprecipitation analysis revealed that the POU specific
      (POUs) domain spanning from aa 91 to 181 of HNF-1alpha is responsible for the
      interaction of NS5A. We also found that the region from aa 121 to 126 of NS5A,
      which is known as the binding motif of the HCV replication factor FKBP8, is
      important for the degradation of HNF-1alpha. A NS5A V121A mutation disrupted the
      NS5A-HNF-1alpha interaction as well as the degradation of HNF-1alpha. Our
      findings suggest that NS5A Val121 is crucial for viral pathogenesis. 

PMID- 25957096
TI  - Isolation of the Thogoto virus from a Haemaphysalis longicornis in Kyoto City,
      Japan.
AB  - Ticks transmit viruses responsible for severe emerging and re-emerging infectious
      diseases, some of which have a significant impact on public health. In Japan,
      little is known about the distribution of tick-borne viruses. In this study, we
      collected and tested ticks to investigate the distribution of tick-borne
      arboviruses in Kyoto, Japan, and isolated the first Thogoto virus (THOV) to our
      knowledge from Haemaphysalis longicornis in far-eastern Asia. The Japanese
      isolate was genetically distinct from a cluster of other isolates from Africa,
      Europe and the Middle East. Various cell lines derived from mammals and ticks
      were susceptible to the isolate, but it was not pathogenic in mice. These results
      advance understanding of the distribution and ecology of THOV. 

PMID- 25957098
TI  - Latent infection of myeloid progenitors by human cytomegalovirus protects cells
      from FAS-mediated apoptosis through the cellular IL-10/PEA-15 pathway.
AB  - Latent infection of primary CD34(+) progenitor cells by human cytomegalovirus
      (HCMV) results in their increased survival in the face of pro-apoptotic signals.
      For instance, we have shown previously that primary myeloid cells are refractory
      to FAS-mediated killing and that cellular IL-10 (cIL-10) is an important survival
      factor for this effect. However, how cIL-10 mediates this protection is unclear.
      Here, we have shown that cIL-10 signalling leading to upregulation of the
      cellular factor PEA-15 mediates latency-associated protection of CD34(+)
      progenitor cells from the extrinsic death pathway.

PMID- 25957099
TI  - Microsphere-Based Rapamycin Delivery, Systemic Versus Local Administration in a
      Rat Model of Renal Ischemia/Reperfusion Injury.
AB  - PURPOSE: The increasing prevalence and treatment costs of kidney diseases call
      for innovative therapeutic strategies that prevent disease progression at an
      early stage. We studied a novel method of subcapsular injection of monodisperse
      microspheres, to use as a local delivery system of drugs to the kidney. METHODS:
      We generated placebo- and rapamycin monodisperse microspheres to investigate
      subcapsular delivery of drugs. Using a rat model of acute kidney injury,
      subcapsular injection of placebo and rapamycin monodisperse microspheres
      (monospheres) was compared to subcutaneous injection, mimicking systemic
      administration. RESULTS: We did not find any adverse effects related to the
      delivery method. Irrespective of the injection site, a similar low dose of
      rapamycin was present in the circulation. However, only local intrarenal delivery
      of rapamycin from monospheres led to decreased macrophage infiltration and a
      significantly lower amount of myofibroblasts in the kidney, where systemic
      administration did not. Local delivery of rapamycin did cause a transient
      increase in the deposition of collagen I, but not of collagen III. CONCLUSIONS:
      We conclude that therapeutic effects can be increased when rapamycin is delivered
      subcapsularly by monospheres, which, combined with low systemic concentrations,
      may lead to an effective intrarenal delivery method.

PMID- 25957100
TI  - Comparison of health-related quality of life among children with cystic fibrosis
      and their parents in two Eastern European countries.
AB  - BACKGROUND: In the optimal care of cystic fibrosis (CF) patients, not only
      medical parameters are respected but also health-related quality of life (HRQOL).
      The aim of our study was to compare HRQOL of CF patients from two Eastern
      European countries. METHODS: 141 patients with CF (6-18 years) and 102 parents
      completed the Cystic Fibrosis Questionnaire-Revised (CFQ-R). Data about disease
      severity, type of children's education and questions about parents' employment
      status were collected. RESULTS: In the patient group, a significant difference
      was found only in Treatment burden, whereas in the parent group, there were
      significant differences in Treatment burden, Emotional functioning, Eating and
      Digestive symptoms between the two countries. School attendance was revealed as
      an important factor influencing HRQOL. CONCLUSIONS: Observed differences in
      evaluation of HRQOL may be caused by different therapeutic and diagnostic
      challenges between countries. To identify possible presence of psychosocial
      problems, monitoring of HRQOL is recommended.

PMID- 25957101
TI  - Neuroimaging and Anxiety: the Neural Substrates of Pathological and Non
      pathological Anxiety.
AB  - Advances in the use of noninvasive neuroimaging to study the neural correlates of
      pathological and non-pathological anxiety have shone new light on the underlying
      neural bases for both the development and manifestation of anxiety. This review
      summarizes the most commonly observed neural substrates of the phenotype of
      anxiety. We focus on the neuroimaging paradigms that have shown promise in
      exposing this relevant brain circuitry. In this way, we offer a broad overview of
      how anxiety is studied in the neuroimaging laboratory and the key findings that
      offer promise for future research and a clearer understanding of anxiety. 

PMID- 25957102
TI  - A modified Mohler technique for patients with unilateral cleft lip based on
      geometric principles--A primary report.
AB  - OBJECTIVE: The Mohler technique is one of the most popular methods to repair
      unilateral cleft lip (UCL) among the modified Millard methods, but it is still
      imperfect. We successfully designed a modified Mohler method based on geometric
      principles and observed its clinical effect. MATERIALS AND METHODS:
      Photogrammetry was performed in 56 patients who underwent UCL repair with the new
      technique. The symmetry ratios were assessed for sn-cphi, cphi-sbal, ch-sbal, ch
      cphi, and vh preoperatively and 1 week after surgery, and were also compared with
      values in healthy control individuals. RESULTS: Preoperatively, all distances on
      the cleft side were shorter to different degrees. One week after surgery, results
      showed well-healed wounds with full, symmetric, and continuous vermilion. On the
      cleft side, the sn-cphi was 6.13% longer than the non-cleft, and the others were
      shorter (cphi-sbal: 5.904%; ch-sbal: 1.760%; ch-cphi: 6.234%). The symmetry
      ratios had differences of significance between preoperative values and those 1
      week after surgery (p = 0.000, respectively). Moreover, the vermilion height on
      the cleft side was 1.026% thicker. When compared with the matched control group,
      with the exception of SRcphi-sbal (p = 0.072) and SRch-sbal (p = 0.139), there
      were significant differences (p = 0.000, respectively). All distances in the
      matched control group were not absolutely symmetric. CONCLUSIONS: The modified
      Mohler technique seems widely applicable, marking accurate, and less flexible.

PMID- 25957103
TI  - Can we use serum copeptin levels as a biomarker in obstructive sleep apnea
      syndrome?
AB  - OBJECTIVE: The aim of this study was to compare serum copeptin levels in patients
      with obstructive sleep apnea syndrome (OSA) and simple snorers without sleep
      apnea; and to investigate relationships between copeptin levels and
      polysomnographic parameters. METHODS: Serum copeptin levels were determined using
      enzyme-linked immunosorbent assay in 47 patients with OSA and 12 patients without
      OSA (control group). Full-night polysomnography was performed in each patient.
      Patients with OSA were divided into three groups according to their Apnea
      Hypopnea Index (AHI) scores: mild OSA (5 < AHI < 15), moderate OSA (15 < AHI <
      30), and severe OSA (AHI > 30). RESULTS: A total of 59 patients were included in
      the study. There were 23 female (39.0%) and 36 male (61.0%) subjects. The range
      of ages of study subjects was between 27 and 63 (mean 44.75 +/- 9.64) years.
      According to the AHI values, patients were classified into four groups: simple
      snoring (n = 13), mild OSA (n = 10), moderate OSA (n = 15), and severe OSA (n =
      21). Statistically significant differences between AHI groups in terms of age,
      Epworth score, and neck circumference. According to multiple comparison results
      for age, the difference between simple snoring and moderate OSA was statistically
      significant. According to multiple comparison results for Epworth score, the
      difference between simple snoring and severe OSA was statistically significant.
      According to multiple comparison results for neck circumference, a similar result
      was found like Epworth Sleepiness Scale score. The difference between AHI groups
      by gender was tested by a Pearson chi(2) test and was found to be statistically
      significant. There was no statistically significant difference among AHI groups
      in terms of copeptin. There was a statistically significant correlation of
      copeptin with AHI during rapid eye movement (REM) sleep; however, the correlation
      coefficient was not sufficiently large. CONCLUSIONS: Increased serum copeptin
      concentration may reflect a response to stress in some diseases. This is well
      documented especially in cardiovascular diseases; however, we could not find any
      difference in OSA groups in terms of copeptin levels.

PMID- 25957104
TI  - The use of anatomically drop-shaped bioactive glass S53P4 implants in the
      reconstruction of orbital floor fractures--A prospective long-term follow-up
      study.
AB  - An isolated fracture of the orbital floor needs reconstruction if there is a
      clear herniation of adipose tissue or of the rectus inferior muscle into the
      maxillary sinus. A prospective study was carried out treating 20 patients with an
      isolated blow-out fracture of the orbital floor or with a combined zygomatico
      orbito-maxillary complex fracture, using a newly designed anatomically drop
      shaped implants made of bioactive glass (BAG) S53P4. Computed tomography (CT) was
      performed immediately postoperatively to confirm the correct position of the
      plate. The patients were followed up for an average of 32 months clinically and
      radiologically with magnetic resonance imaging (MRI) for an average of 31 months.
      None of the patients had any signs of complications related to the implant and
      the clinical outcome was very good. None of the patients had persisting diplopia.
      The level of the pupillas was normal in 15 of 20 patients. Minor hypo-ophthalmos
      ranging from 0.5 to 1.0 mm was observed in three patients, and moderate hypo
      ophthalmos of 2.0 mm was seen in one patient. Hyperophthalmos of 1.0 mm was seen
      in one patient. Minor enophthalmos on the operated side ranging from 0.5 to 1.0
      mm was seen in eight patients. Mild to moderate paraesthesia of the infraorbital
      nerve was observed in six patients. The immediate postoperative CT and the long
      term follow-up MRI revealed that the drop-shaped BAG implants retained their
      correct position in the orbital floor and did not show any evidence of losing
      their original shape or material resorption. No adverse tissue reaction was
      associated with the material. Due to the anatomical drop shape, the implants
      could successfully maintain the orbital volume and compensate for the retrobulbar
      adipose tissue atrophy.

PMID- 25957105
TI  - Systematic review of "filling" procedures for lip augmentation regarding types of
      material, outcomes and complications.
AB  - BACKGROUND: The ideal lip augmentation technique provides the longest period of
      efficacy, lowest complication rate, and best aesthetic results. A myriad of
      techniques have been described for lip augmentation, but the optimal approach has
      not yet been established. This systematic review with meta-regression will focus
      on the various filling procedures for lip augmentation (FPLA), with the goal of
      determining the optimal approach. METHODS: A systematic search for all English,
      French, Spanish, German, Italian, Portuguese and Dutch language studies involving
      FPLA was performed using these databases: Elsevier Science Direct, PubMed,
      Highwire Press, Springer Standard Collection, SAGE, DOAJ, Sweetswise, Free E
      Journals, Ovid Lippincott Williams & Wilkins, Willey Online Library Journals, and
      Cochrane Plus. The reference section of every study selected through this
      database search was subsequently examined to identify additional relevant
      studies. RESULTS: The database search yielded 29 studies. Nine more studies were
      retrieved from the reference sections of these 29 studies. The level of evidence
      ratings of these 38 studies were as follows: level Ib, four studies; level IIb,
      four studies; level IIIb, one study; and level IV, 29 studies. Ten studies were
      prospective. CONCLUSIONS: This systematic review sought to highlight all the
      quality data currently available regarding FPLA. Because of the considerable
      diversity of procedures, no definitive comparisons or conclusions were possible.
      Additional prospective studies and clinical trials are required to more
      conclusively determine the most appropriate approach for this procedure. LEVEL OF
      EVIDENCE: IV.

PMID- 25957106
TI  - Application of high resolution synchrotron micro-CT radiation in dental implant
      osseointegration.
AB  - The purpose of this study was to describe a refined method using high-resolution
      synchrotron radiation microtomography (SRmicro-CT) to evaluate osseointegration
      and peri-implant bone volume fraction after titanium dental implant insertion.
      SRmicro-CT is considered gold standard evaluating bone microarchitecture. Its
      high resolution, high contrast, and excellent high signal-to-noise-ratio all
      contribute to the highest spatial resolutions achievable today. Using SRmicro-CT
      at a voxel size of 5 MUm in an experimental goat mandible model, the peri-implant
      bone volume fraction was found to quickly increase to 50% as the radial distance
      from the implant surface increased, and levelled out to approximately 80% at a
      distance of 400 MUm. This method has been successful in depicting the bone and
      cavities in three dimensions thereby enabling us to give a more precise answer to
      the fraction of the bone-to-implant contact compared to previous methods. 

PMID- 25957107
TI  - Effect of Chinese herbal medicine on vascular functions during 60-day head-down
      bed rest.
AB  - PURPOSE: Chinese herbal medicine is a promising countermeasure against
      cardiovascular dysfunction associated with a sedentary lifestyle. We examined the
      impact of the Chinese herb, Taikong Yangxin, on the micro- and macrovascular
      dysfunction associated with a 60-day bed rest. METHODS: Fourteen healthy men were
      randomly divided into two groups: those given herbal supplement, and the control
      group; the two groups underwent a 60-day bed rest. The macrovasculature was
      assessed by sonography. Skin microvascular functions were assessed with laser
      Doppler. The plasma level of endothelial microparticles (EMPs), markers of
      endothelial injury, was determined. RESULTS: Bed rest induced a 33 % decrease in
      the femoral artery diameter and compliance whereas carotid wall thickness,
      diameter, and compliance remained unchanged. The early phase of endothelium
      dependent vasodilation to ACh was unmodified by bed rest, while the late phase
      was reduced by 30 % along with a twofold increase in EMPs. In those given Taikong
      Yangxin, the early phase was amplified by 2.5-fold, and the effects of bed rest
      on the late phase were prevented. CONCLUSION: These findings indicate that
      Taikong Yangxin ameliorates endothelium-dependent vasodilation, likely by
      improving the NO pathway. The study suggests Taikong Yangxin as a new
      countermeasure to prevent the changes in microvascular function induced by
      physical inactivity.

PMID- 25957108
TI  - Re: Use of Phosphodiesterase Type 5 Inhibitors May Adversely Impact Biochemical
      Recurrence after Radical Prostatectomy: U. Michl, F. Molfenter, M. Graefen, P.
      Tennstedt, S. Ahyai, B. Beyer, L. Budaus, A. Haese, H. Heinzer, S. J. Oh, G.
      Salomon, T. Schlomm, T. Steuber, I. Thederan, H. Huland and D. Tilki J Urol
      2015;193:479-483.

PMID- 25957109
TI  - Regarding "Distal peripheral neuropathy after open and arthroscopic shoulder
      surgery: an under-recognized complication".

PMID- 25957110
TI  - Regarding "Distal peripheral neuropathy after open and arthroscopic shoulder
      surgery: an under-recognized complication".

PMID- 25957111
TI  - Surgical management of the infected reversed shoulder arthroplasty: a French
      multicenter study of reoperation in 32 patients.
AB  - BACKGROUND: In a retrospective multicenter study, we evaluated the efficiency and
      outcomes of the different therapeutic options for infection after reversed
      shoulder arthroplasty. METHODS: Thirty-two patients were reoperated on for
      infection after reversed shoulder arthroplasty between 1996 and 2011. The mean
      age was 71 (55-83) years. The involved implants were primary prostheses in 23
      cases and revision prostheses in 9 cases. The average preoperative Constant score
      was 34 (11-69). Six of these patients needed 2 successive procedures. A total of
      38 procedures were performed: debridement (13), 1-stage (5) or 2-stage revision
      (14), or implant removal (6). At last follow-up (mean, 36 months; range, 12-137
      months), every patient had clinical, biologic, and radiographic evaluation.
      RESULTS: Infections were largely caused by coagulase-negative staphylococci (56%)
      and Propionibacterium acnes (59%). The complication rate was 26%. At last follow
      up, 26 patients were free of infection (81%). The final Constant score was 46 (12
      75). After debridement with implant retention, the mean Constant score was 51 (29
      75), but the healing rate was only 54%. Implant revision (1 or 2 stage) led to
      better functional results than implant removal (46 vs. 25; P = .001), with
      similar healing rates (73% and 67%, respectively). Patients with low initial
      impairment (Constant score > 30) were not significantly improved by surgical
      treatment. CONCLUSION: Debridement is the less aggressive option but exposes
      patients to healing failure. It should be proposed as a first treatment attempt.
      Revision of the implant is technically challenging but preserves shoulder
      function, with no higher rate of residual infection compared with implant
      removal.

PMID- 25957112
TI  - Preseason shoulder range of motion screening as a predictor of injury among youth
      and adolescent baseball pitchers.
AB  - BACKGROUND: Approximately 6 million youngsters play organized baseball yearly,
      and injuries are common. Defining of risk factors for injuries in the throwing
      shoulder has largely been confined to the professional thrower. Unfortunately,
      these risk factors apply to only 1% of pitchers at risk for injury. Risk factors
      for injury in youth pitchers have received far less attention than those in more
      mature professional pitchers. Development of such an understanding would help
      clarify injury prevention efforts for the other 99% of pitchers actively
      participating in competitive baseball. This study intended to determine the
      ability of range of motion (ROM) measures to predict arm injuries in baseball
      pitchers aged 8 to 18 years. METHODS: Supine passive shoulder ROM was assessed in
      115 pitchers with a digital inclinometer. Two trials of ROM were measured before
      the season. Arm injuries were prospectively tracked. Receiver operating
      characteristic curves were used to identify athletes who were at high risk for
      injury. Statistical significance was set a priori (alpha = .05). RESULTS: There
      were 33 injured and 82 uninjured pitchers. Side-to-side differences of horizontal
      adduction >15 degrees  and internal rotation >13 degrees  may discriminate
      between those adolescent pitchers at 4 and 6 times greater risk of injury,
      respectively. CONCLUSION: Preseason ROM differences were able to identify those
      adolescents at high risk for injury during the season. It appears that the risk
      profile for adolescent pitchers includes horizontal adduction differences that
      differ from the established prospective profile in adult pitchers.

PMID- 25957114
TI  - Fine-mapping and validating qHTSF4.1 to increase spikelet fertility under heat
      stress at flowering in rice.
AB  - KEY MESSAGE: This study fine mapped and validated a QTL on rice chromosome 4 that
      increases spikelet fertility under high temperature (over 37  degrees C) at the
      flowering stage. Climate change has a negative effect on crop production and food
      security. Understanding the genetic mechanism of heat tolerance and developing
      heat-tolerant varieties is essential to cope with future global warming.
      Previously, we reported on a QTL (qHTSF4.1) from an IR64/N22 population
      responsible for rice spikelet fertility under high-temperature stress at the
      flowering stage. To further fine map and validate the effect of qHTSF4.1, PCR
      based SNP markers were developed and used to genotype BC2F2, BC3F2, BC3F3, and
      BC5F2 populations from the same cross. The interval of the QTL was narrowed down
      to about 1.2 Mb; however, further recombination was not identified even with a
      large BC5F2 population that was subsequently developed and screened. The sequence
      in the QTL region is highly conserved and a large number of genes in the same
      gene family were observed to be clustered in the region. The QTL qHTSF4.1
      consistently increased spikelet fertility in all of the backcross populations.
      This was confirmed using 24 rice varieties. Most of the rice varieties with the
      QTL showed a certain degree of heat tolerance under high-temperature conditions.
      In a BC5F2 population with clean background of IR64, QTL qHTSF4.1 increased
      spikelet fertility by about 15%. It could be an important source for enhancing
      heat tolerance in rice at the flowering stage. PCR-based SNP markers developed in
      this study can be used for QTL introgression and for pyramiding with other
      agronomically important QTLs/genes through marker-assisted selection.

PMID- 25957113
TI  - Microarchitectural and mechanical characterization of the sickle bone.
AB  - Individuals with sickle cell disease often experience acute and chronic bone pain
      due to occlusive events within the tissue vasculature that result in ischemia,
      necrosis, and organ degeneration. Macroscopically, sickle bone is identified in
      clinical radiographs by its reduced mineral density, widening of the marrow
      cavity, and thinning of the cortical bone due to the elevated erythroid
      hyperplasia accompanying the disease. However, the microstructural architecture
      of sickle bone and its role in mechanical functionality is largely unknown. This
      study utilized micro-CT and biomechanical testing to determine the relationship
      between the bone morphology, tissue mineral density, and trabecular and cortical
      microarchitecture of 10- and 21-week-old femurs from transgenic sickle male mice
      and littermates with sickle trait, as well as a wild-type control. While bone
      tissue mineral density did not vary among the genotypes at either age, variation
      in bone microstructure were observed. At 10 weeks, healthy and trait mice
      exhibited similar morphology within the cortical and trabecular bone, while
      sickle mice exhibited highly connected trabeculae. Within older femurs, sickle
      and trait specimens displayed significantly fewer trabeculae, and the remaining
      trabeculae had a more deteriorated geometry based on the structure model index.
      Thinning of the cortical region in sickle femurs contributed to the displayed
      flexibility with a significantly lower elastic modulus than the controls at both
      10- and 21-weeks old. Wild-type and trait femurs generally demonstrated similar
      mechanical properties; however, trait femurs had a significantly higher modulus
      than sickle and wild-type control at 21-weeks. Overall, these data indicate that
      the progressive damage to the microvasculature caused by sickle cell disease,
      results in deleterious structural changes in the bone tissue's microarchitecture
      and mechanics. 

PMID- 25957115
TI  - Development of Gossypium anomalum-derived microsatellite markers and their use
      for genome-wide identification of recombination between the G. anomalum and G.
      hirsutum genomes.
AB  - KEY MESSAGE: We reported the first development of Gossypium anomalum -derived
      microsatellite markers and identification of recombination between sexually
      incompatible species by a synthesized hexaploid on genome level. To continue to
      develop improved cotton varieties, it is essential to transfer desired characters
      from diploid wild cotton species such as Gossypium anomalum to cultivated
      allotetraploid cotton species. However, interspecific reproductive barriers limit
      gene transfer between species. In a previous study, we used colchicine treatment
      to produce a synthesized hexaploid derived from an interspecific hybrid between
      Gossypium hirsutum and G. anomalum and demonstrated its hybridity and doubled
      status using morphological, cytological and molecular marker methods. In the
      current study, to effectively monitor G. anomalum genome components in the G.
      hirsutum background, we developed 5974 non-redundant G. anomalum-derived SSR
      primer pairs using RNA-Seq technology, which were combined with a publicly
      available physical map. Based on this combined map and segregation data from the
      BC2F1 population, we identified a set of 230 informative G. anomalum-specific SSR
      markers distributed on the chromosomes, which cover 95.72% of the cotton genome.
      After analyzing BC2F1 segregation data, 50 recombination types from 357
      recombination events were identified, which cover 81.48% of the corresponding G.
      anomalum genome. A total of 203 recombination events occurred on chromosome 11,
      accounting for 56.86% of the recombination events on all chromosomes.
      Recombination hotspots were observed at marker intervals JAAS1148-NAU5100 on
      chromosome 1 and JAAS0426-NAU998 on chromosome 2. Therefore, all G. anomalum
      chromosomes are capable of recombining with At chromosomes in G. hirsutum. This
      study represents an important step towards introgressing desirable traits into
      cultivated cotton from the wild cotton species G. anomalum.

PMID- 25957116
TI  - D-dimer testing cannot rule out thromboembolism after major lower extremity
      arthroplasties and thromboprophylaxis treatment.
AB  - PURPOSE: Our previous study showed, for the first time, that a guideline
      recommended thromboprophylactic strategy reduced the prevalence of venous
      thromboembolism (VTE) including venous thromboembolism and pulmonary embolism
      after arthroplasties of the major lower extremities, such as total hip
      arthroplasty (THA) or total or partial knee arthroplasty (TPKA), to 4.4 %. In
      this retrospective study, we examined the diagnostic value of D-dimer for VTE and
      try to confirm the low prevalence of VTE after THA or TPKA. METHODS: This was a
      retrospective study including 380 procedures of 361 patients who underwent
      elective 129 TPKA or 251 THA, as well as multidetector computed tomography (MDCT)
      on postoperative day 7 with D-timer testing to screen for VTE. In 303 of 380
      procedures, D-timer testing was performed on the same day as MDCT. The
      antithrombotic prophylaxes included medical and mechanical therapy and early
      ambulation. RESULTS: The prevalence of VTE was 4.5 % (17 cases) (95 % confidence
      interval 2.4-6.6 %). The D-dimer level was significantly greater in patients with
      VTE than in those without (13.4 +/- 11.1 vs 10.1 +/- 6.5 MUg/mL). At the lowest
      cut-off value of 4.0 MUg/mL, D-dimer testing ruled out VTE in only 26 of 303
      cases with 1 (6 %) false negative result. CONCLUSIONS: The low incidence of
      postoperative VTE with the strict anticoagulation strategy was confirmed in this
      validation study. D-dimer testing is not useful for excluding VTE postoperatively
      in patients who undergo THA or TPKA.

PMID- 25957117
TI  - PD-1 and CD103 Are Widely Coexpressed on Prognostically Favorable Intraepithelial
      CD8 T Cells in Human Ovarian Cancer.
AB  - alphaE(CD103)beta7 is a TGFbeta-regulated integrin that mediates retention of
      lymphocytes in peripheral tissues by binding to E-cadherin expressed on
      epithelial cells. We recently reported that alphaE(CD103)beta7 specifically
      demarcates intraepithelial CD8(+) tumor-infiltrating lymphocytes (CD8 TIL) in
      ovarian cancer and that CD103(+) TIL have a surface profile consistent with an
      active effector phenotype (HLA-DR(+), Ki67(+), and CD127(lo)). These findings led
      us to hypothesize that, over time, CD103-mediated retention of CD8 TIL within the
      tumor epithelium might result in chronic stimulation by tumor antigen, which in
      turn might lead to an exhausted phenotype. To investigate this possibility, we
      evaluated PD-1 expression in a large cohort of ovarian tumors (N = 489) with
      known CD103(+) TIL content. PD-1(+) cells were present in 38.5% of high-grade
      serous carcinomas (HGSC), but were less prevalent in other histologic subtypes.
      PD-1(+) TIL were strongly associated with increased disease-specific survival in
      HGSC (HR, 0.4864; P = 0.0007). Multicolor immunohistochemistry and flow cytometry
      revealed a high degree of PD-1 and CD103 coexpression, specifically within the
      CD8 TIL compartment. PD-1(+)CD103(+) CD8 TIL were quiescent when assessed
      directly ex vivo yet were capable of robust cytokine production after
      pharmacologic stimulation. Moreover, they showed negligible expression of
      additional exhaustion-associated markers, including TIM-3, CTLA-4, and LAG-3.
      Thus, as hypothesized, CD103(+) CD8 TIL express PD-1 and appear quiescent in the
      tumor microenvironment. However, these cells retain functional competence and
      demonstrate strong prognostic significance. We speculate that, after standard
      treatment, PD-1(+)CD103(+) CD8 TIL might regain functional antitumor activity, an
      effect that potentially could be augmented by immune modulation.

PMID- 25957118
TI  - Neurotoxicity of trimethyltin in rat cochlear organotypic cultures.
AB  - Trimethyltin (TMT), which has a variety of applications in industry and
      agricultural, is a neurotoxin that is known to affect the auditory system as well
      as central nervous system of humans and experimental animals. However, the
      mechanisms underlying TMT-induced auditory dysfunction are poorly understood. To
      gain insights into the neurotoxic effect of TMT on the peripheral auditory
      system, we treated cochlear organotypic cultures with concentrations of TMT
      ranging from 5 to 100 MUM for 24 h. Interestingly, TMT preferentially damaged
      auditory nerve fibers and spiral ganglion neurons in a dose-dependent manner, but
      had no noticeable effects on the sensory hair cells at the doses employed. TMT
      induced damage to auditory neurons was associated with significant soma
      shrinkage, nuclear condensation, and activation of caspase-3, biomarkers
      indicative of apoptotic cell death. Our findings show that TMT is exclusively
      neurotoxicity in rat cochlear organotypic culture and that TMT-induced auditory
      neuron death occurs through a caspase-mediated apoptotic pathway. 

PMID- 25957119
TI  - Changes over the last decade in carotid atherosclerosis in patients with end
      stage kidney disease.
AB  - OBJECTIVE: Therapies for chronic kidney disease have changed greatly over the
      last decade. The aim of this study was to examine the changes in the clinical
      characteristics and carotid atherosclerosis of patients with end-stage kidney
      disease (ESKD) over the last 9 years. METHODS: A cross-sectional study of 150
      consecutive patients with ESKD who had initiated maintenance dialysis between
      January 2005 and December 2013 was conducted. The patients' mean age was 68 +/-
      13 years. The group comprised 73% men, and 63% of the patients had diabetic
      nephropathy. The carotid artery-intima media thicknesses and the plaque scores
      (PS) were measured using carotid artery ultrasonography within 3 months of
      dialysis initiation. Changes in the patients' carotid atherosclerosis and
      clinical characteristics over the years were examined by categorizing the
      patients into 3 groups representing 3-year intervals based on when dialysis was
      initiated. RESULTS: The PS declined from 12.8 to 5.4 (P = 0.001). Low-density
      lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol
      levels declined over the 9-year period (P = 0.005 and P = 0.006, respectively),
      and the ratio of statin users increased markedly from 24% to 54% (P = 0.001).
      Univariate regression analysis identified a positive correlation between the PS
      and LDL-C (r = 0.281; P = 0.01), and a strong positive correlation was found
      between the PS and LDL-C after adjusting for various risk factors for
      atherosclerosis. CONCLUSION: Carotid atherosclerosis in patients with ESKD has
      decreased over the past 9 years, which may be a consequence of improvements in
      dyslipidemia management.

PMID- 25957120
TI  - Comparison of angiotensin-(1-7), losartan and their combination on
      atherosclerotic plaque formation in apolipoprotein E knockout mice.
AB  - AIMS: Inhibition of the classical renin-angiotensin system (RAS) has been proved
      to reduce atherosclerosis. Recently, angiotensin-(1-7) [Ang-(1-7)], a new
      component of RAS, has been shown to attenuate atherosclerosis formation. However,
      direct comparison of Ang-(1-7) and angiotensin II type 1 receptor blocker (ARB)
      on atherogenesis is sparse. Here, we investigated whether large dose of Ang-(1-7)
      and losartan are equivalent or the combination of both is superior in reducing
      atherosclerotic plaque formation. METHODS AND RESULTS: In vivo, we established an
      atherosclerosis model in ApoE-/- mice. All mice were fed a high fat diet during
      experiments. Mice were divided into control, Ang-(1-7), losartan, Ang-(1
      7)+losartan groups for 4 weeks treatment. Ang-(1-7) did not change the blood
      pressure (BP) levels, while losartan produced a significant decrease in systolic
      BP. The attenuation of Ang-(1-7) and losartan in atherosclerosis plaque formation
      was similar. However, the decrease of atherosclerosis in mice with combination of
      Ang-(1-7) and losartan was more remarkable relative to that of Ang-(1-7) or
      losartan alone. The decreases of macrophages infiltration, superoxide production
      and improvement of endothelium function in aortic lesions were more significant
      in combination group. In vitro study, we found that combination of Ang-(1-7) and
      losartan notably inhibited VSMCs proliferation and migration. CONCLUSIONS: The
      anti-atherosclerosis effects of Ang-(1-7) and losartan in early lesion formation
      were equivalent. Combination use of both agents further enhanced the beneficial
      effects. Ang-(1-7) might add additional beneficial effect for patients with
      adequate ARB treatment.

PMID- 25957121
TI  - Analysis of medial deviation of center of pressure after initial heel contact in
      forefoot varus.
AB  - BACKGROUND/PURPOSE: After initial heel contact, the rearfoot everts and causes
      medial deviation of the center of pressure (CoP). Although rearfoot angle in
      single-limb stance has been associated with forefoot varus (FV) >= 8 degrees ,
      medial CoP deviation has not. METHODS: After 12 participants with FV < 8 degrees 
      (neutral group) and 11 participants with FV >= 8 degrees  (FV group) stepped one
      heel initially onto an array of pressure sensors parallel to its Y coordinate
      axis, when the CoP of array deviated most medially, the X coordinate of the CoP
      of each row was calculated to find the most medial CoP of the row. Starting since
      the row with the most medial CoP just began to have the same sensors with
      pressures >0 kPa as when it had the most medial CoP, the medial deviations of the
      CoP of the array, the most medial CoP of the row, and its relative position in
      the row (CoP%), were compared between neutral and FV groups. RESULTS: The medial
      deviations of the most medial CoP of the row (1.1 +/- 0.6 vs. 1.6 +/- 0.3 mm, p =
      0.049) and CoP% (2.9 +/- 1.4 vs. 4.2 +/- 1.1%, p = 0.023) were significantly
      different between neutral and FV groups, whereas that of the CoP of the array
      (1.1 +/- 0.6 vs. 1.4 +/- 0.6 mm, p = 0.36) was not. CONCLUSION: The most medial
      CoP of the row and CoP% detected increased medial CoP deviation in FV >= 8
      degrees , and may be applied to other clinical conditions where rearfoot angle
      and CoP of the array after initial heel contact cannot detect significant
      differences.

PMID- 25957122
TI  - Occurrence of Clostridium difficile in two types of wastewater treatment plants.
AB  - Wastewater is a potential environmental source of Clostridium difficile, although
      a direct link with community-acquired C. difficile infection (CA-CDI) in humans
      has not yet been established. The present study was performed to determine the
      occurrence of C. difficile in two types of wastewater treatment plants (WWTPs) in
      Isfahan, Iran. A total of 95 samples were taken from a conventional activated
      sludge treatment plant and a waste stabilization ponds system, and analyzed for
      the presence of C. difficile. C. difficile was found in 13.6% (3/22) of digested
      sludge samples. However, no C. difficile was detected in inlet and outlet samples
      or in raw sludge of activated sludge. C. difficile was also detected in 5% (2/40)
      of the samples from waste stabilization ponds. Polymerase chain reaction (PCR)
      analysis showed that all strains of C. difficile detected were toxigenic (tcdB
      gene positive). This study shows that C. difficile was present in WWTPs, which
      might constitute a potential source of community-acquired C. difficile infection.

PMID- 25957123
TI  - Preparing long probes by an asymmetric polymerase chain reaction-based approach
      for multiplex ligation-dependent probe amplification.
AB  - To clearly discriminate the results of simultaneous screening and quantification
      of up to 40 different targets-DNA sequences, long probes from 100 to 500 nt,
      rather than smaller or similar-sized synthetic ones, were adopted for multiplex
      ligation-dependent probe amplification (MLPA). To prepare the long probes,
      asymmetric polymerase chain reaction (PCR) was employed to introduce non
      complementary stuffers in between the two parts of the MLPA probe with specially
      designed primers, then restriction enzymes were selected to digest the double
      stranded DNAs, and finally polyacrylamide gel electrophoresis was used to purify
      the single-stranded DNAs (i.e., the long probes). By using this approach, 12 long
      probes were prepared and used to identify genetically modified (GM) maize. Our
      experimental results show that the prepared long probes were in full accordance
      with the designed ones and could be assembled in 4-, 7-, and 10-plex MLPA
      analysis without losing result specificity and accuracy, showing they were as
      effective and reliable in MLPA analysis as those prepared with M13-derived
      vectors. This novel asymmetric PCR-based approach does not need expensive
      equipment, special reagents, or complicated operations when compared with
      previous methods. Therefore, our new approach could make MLPA analysis more
      independent, efficient, and economical.

PMID- 25957125
TI  - Phagocytosis-coupled flow cytometry for detection and size discrimination of
      anionic polystyrene particles.
AB  - Flow cytometry was evaluated for its capacity to detect and distinguish a wide
      size range (20-2000 nm) of fluorescent polystyrene particles (PSPs). Side scatter
      and fluorescence parameters could predict dispersed PSP sizes down to 200 nm, but
      the forward scatter parameter was not discriminatory. Confocal microscopy of flow
      sorted fractions confirmed that dispersed PSPs appeared as a single sharp peak on
      fluorescence histograms, whereas agglomerated PSPs were detected as smaller
      adjacent peaks. Particles as small as 200 nm could also be detected by flow
      cytometry after they were first phagocytized by J774A.1 murine macrophages.
      Confocal microscopy demonstrated that these PSPs were internalized within the
      cytoplasm. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and
      calcein-AM (acetoxymethyl ester) assays showed that they were not cytotoxic.
      Internalized PSP size correlated to both cellular side scatter (R(2)=0.9821) and
      fluorescence intensity (R(2)=0.9993). Furthermore, PSPs of various sizes could be
      distinguished when J774A.1 cells were loaded with a single size of PSP and mixed
      with cells containing other sizes. However, spectra of cells loaded with a
      mixture of PSP sizes resembled those containing only the largest PSP. These data
      demonstrate the capacity and limitations of phagocytosis-coupled flow cytometry
      to distinguish between dispersed and agglomerated states and detect a wide size
      range of particles.

PMID- 25957124
TI  - All-in-one assay for beta-d-galactoside sialyltransferases: Quantification of
      productive turnover, error hydrolysis, and site selectivity.
AB  - Sialyltransferases are important enzymes of glycobiology and the related
      biotechnologies. The development of sialyltransferases calls for access to quick,
      inexpensive, and robust analytical tools. We have established an assay for
      simultaneous characterization of sialyltransferase activity, error hydrolysis,
      and site selectivity. The described assay does not require expensive substrates,
      is very sensitive (limit of detection=0.3 MUU), and is easy to perform. It is
      based on sialylation of nitrophenyl galactosides; the products thereof are
      separated and quantified by ion pair reversed phase high-performance liquid
      chromatography with ultraviolet detection.

PMID- 25957126
TI  - A continuous spectrophotometric assay for monitoring adenosine 5'-monophosphate
      production.
AB  - A number of biologically important enzymes release adenosine 5'-monophosphate
      (AMP) as a product, including aminoacyl-tRNA synthetases, cyclic AMP (cAMP)
      phosphodiesterases, ubiquitin and ubiquitin-like ligases, DNA ligases, coenzyme A
      (CoA) ligases, polyA deadenylases, and ribonucleases. In contrast to the
      abundance of assays available for monitoring the conversion of adenosine 5'
      triphosphate (ATP) to ADP, there are relatively few assays for monitoring the
      conversion of ATP (or cAMP) to AMP. In this article, we describe a homogeneous
      assay that continuously monitors the production of AMP. Specifically, we have
      coupled the conversion of AMP to inosine 5'-monophosphate (IMP) (by AMP
      deaminase) to the oxidation of IMP (by IMP dehydrogenase). This results in the
      reduction of oxidized nicotine adenine dinucleotide (NAD(+)) to reduced nicotine
      adenine dinucleotide (NADH), allowing AMP formation to be monitored by the change
      in the absorbance at 340 nm. Changes in AMP concentrations of 5 MUM or more can
      be reliably detected. The ease of use and relatively low expense make the AMP
      assay suitable for both high-throughput screening and kinetic analyses.

PMID- 25957127
TI  - Detection of 3-phenoxybenzoic acid in river water with a colloidal gold-based
      lateral flow immunoassay.
AB  - 3-Phenoxybenzoic acid (3-PBA) is a general metabolite of synthetic pyrethroids.
      It could be used as a generic biomarker for multiple pyrethroids exposure for
      human or pyrethroid residues in the environment. In this study, monoclonal
      antibodies (mAbs) against 3-PBA were developed by using PBA-bovine serum albumin
      (BSA) as an immunogen. In the competitive enzyme-linked immunosorbent assay
      (ELISA) format, the I50 and I10 values of purified mAbs were 0.63 and 0.13
      MUg/ml, respectively, with a dynamic range between 0.19 and 2.04 MUg/ml. Then,
      the colloidal gold (CG)-based lateral flow immunoassay was established based on
      the mAbs. The working concentration of coating antigen and CG-labeled antibodies
      and the blocking effects were investigated to get optimal assay performance. The
      cutoff value for the assay was 1 MUg/ml 3-PBA, and the detection time was within
      10 min. A total of 40 river water samples were spiked with 3-PBA at different
      levels and determined by the lateral flow immunoassay without any sample
      pretreatments. The negative false rate was 2.5%, and no positive false results
      were observed at these levels. This lateral flow immunoassay has the potential to
      be an on-site screening method for monitoring 3-PBA or pyrethroid residues in
      environmental samples.

PMID- 25957128
TI  - Pre-labeling of diverse protein samples with a fixed amount of Cy5 for sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis analysis.
AB  - A pre-labeling protocol based on Cy5 N-hydroxysuccinimide (NHS) ester labeling of
      proteins has been developed for one-dimensional sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) analysis. We show that a fixed
      amount of sulfonated Cy5 can be used in the labeling reaction to label proteins
      over a broad concentration range-more than three orders of magnitude. The optimal
      amount of Cy5 was found to be 50 to 250pmol in 20MUl using a Tris-HCl labeling
      buffer at pH 8.7. Labeling protein samples with a fixed amount of dye in this
      range balances the requirements of sub-nanogram detection sensitivity and low dye
      to-protein (D/P) ratios for SDS-PAGE. Simulations of the labeling reaction
      reproduced experimental observations of both labeling kinetics and D/P ratios.
      Two-dimensional electrophoresis was used to examine the labeling of proteins in a
      cell lysate using both sulfonated and non-sulfonated Cy5. For both types of Cy5,
      we observed efficient labeling across a broad range of molecular weights and
      isoelectric points. 

PMID- 25957130
TI  - A Dangerous Ride: A Case of Traumatic Splenic Rupture.

PMID- 25957129
TI  - Intestinal Failure: The Long and Short of the Matter.

PMID- 25957131
TI  - Cooperation of distinct Rac-dependent pathways to stabilise E-cadherin adhesion.
AB  - The precise mechanisms via which Rac1 is activated by cadherin junctions are not
      fully known. In keratinocytes Rac1 activation by cadherin junctions requires EGFR
      signalling, but how EGFR does so is unclear. To address which activator could
      mediate E-cadherin signalling to Rac1, we investigated EGFR and two Rac1 GEFs,
      SOS1 and DOCK180. EGFR RNAi prevented junction-induced Rac1 activation and led to
      fragmented localization of E-cadherin at cadherin contacts. In contrast,
      depletion of another EGFR family member, ErbB3, did not interfere with either
      process. DOCK180 RNAi, but not SOS1, prevented E-cadherin-induced Rac1
      activation. However, in a strong divergence from EGFR RNAi phenotype, DOCK180
      depletion did not perturb actin recruitment or cadherin localisation at
      junctions. Rather, reduced DOCK180 levels impaired the resistance to mechanical
      stress of pre-formed cell aggregates. Thus, within the same cell type, EGFR and
      DOCK180 regulate Rac1 activation by newly-formed contacts, but control separate
      cellular events that cooperate to stabilise junctions. 

PMID- 25957132
TI  - Usefulness of peroral endoscopic myotomy for treating achalasia in children:
      experience from a single center.
AB  - INTRODUCTION: Achalasia is a rare esophageal motility disorder in the pediatric
      population. Peroral endoscopic myotomy (POEM) has been demonstrated to be
      effective and safe for the treatment of achalasia as a novel endoscopic
      technique, but data involving its utility in pediatric patients are limited. We
      aimed to assess the safety and efficacy of POEM for pediatric patients with
      achalasia. MATERIALS AND METHODS: Between July 2012 and August 2014, five
      consecutive pediatric patients (2 female and 3 male, with a median age of 15
      years) with achalasia underwent POEM in our center. Diagnosis was based on
      symptoms, manometry, radiology and endoscopy. Preoperative and postoperative
      symptoms scores, and manometry outcomes were recorded and analyzed. RESULTS:
      Procedure was performed successfully in all patients, and the median time
      required for the procedure was 50 min (range 40-90 min). There were no
      mortalities and no serious intraoperative and postoperative complications. The
      median length of myotomy was 8 cm (range 6-11 cm). During a median follow-up
      period of 18 months, treatment success (Eckardt score <=3) was achieved in all
      patients. There was a significant improvement of symptoms relief, dysphagia score
      and lower esophageal sphincter pressure decrease after POEM. No patient developed
      gastroesophageal reflux disease. CONCLUSION: Our study suggests that POEM is a
      safe and effective technique for treating pediatric achalasia. Further studies
      with long-term follow-up in large-volume pediatric patients are warranted to
      clearly define the durability of the procedure.

PMID- 25957133
TI  - Spatial pattern separation differences in older adult carriers and non-carriers
      for the apolipoprotein E epsilon 4 allele.
AB  - We examined the performance of healthy young (n=57) and older adults (n=43)
      genotyped as apolipoprotein E-epsilon4 (APOE-epsilon4) carriers or APOE-epsilon4
      non-carriers on a delayed match-to-sample task involving varying degrees of
      spatial interference hypothesized to assess spatial pattern separation. Older
      adult epsilon4 carriers were further divided into "impaired" and "unimpaired"
      groups based on their performance on a standardized test of verbal memory. We
      found that performance on the spatial pattern separation test increased as a
      function of decreased spatial interference across all groups. The older epsilon4
      carriers in the impaired group performed significantly worse (p<.05) than
      unimpaired epsilon4 carriers, epsilon4 non-carriers, and young adults. The data
      suggest that spatial pattern separation may be less efficient in a subset of
      healthy older adults with subtle memory decline who are carriers of the epsilon4
      allele. However, pattern separation performance may be comparable to that of
      young adults in a subset of older adult epsilon4 carriers and more broadly among
      non-carriers. Our findings offer additional evidence that pattern separation may
      vary in older adults, and they provide novel insight into pattern separation
      efficiency in epsilon4-positive older adults. 

PMID- 25957134
TI  - Latent memory facilitates relearning through molecular signaling mechanisms that
      are distinct from original learning.
AB  - A highly conserved feature of memory is that it can exist in a latent, non
      expressed state which is revealed during subsequent learning by its ability to
      significantly facilitate (savings) or inhibit (latent inhibition) subsequent
      memory formation. Despite the ubiquitous nature of latent memory, the mechanistic
      nature of the latent memory trace and its ability to influence subsequent
      learning remains unclear. The model organism Aplysia californica provides the
      unique opportunity to make strong links between behavior and underlying cellular
      and molecular mechanisms. Using Aplysia, we have studied the mechanisms of
      savings due to latent memory for a prior, forgotten experience. We previously
      reported savings in the induction of three distinct temporal domains of memory:
      short-term (10min), intermediate-term (2h) and long-term (24h). Here we report
      that savings memory formation utilizes molecular signaling pathways that are
      distinct from original learning: whereas the induction of both original
      intermediate- and long-term memory in naive animals requires mitogen activated
      protein kinase (MAPK) activation and ongoing protein synthesis, 2h savings memory
      is not disrupted by inhibitors of MAPK or protein synthesis, and 24h savings
      memory is not dependent on MAPK activation. Collectively, these findings reveal
      that during forgetting, latent memory for the original experience can facilitate
      relearning through molecular signaling mechanisms that are distinct from original
      learning. 

PMID- 25957135
TI  - The Relationship Between Digit Ratio (2D:4D) and Sexual Orientation in Men from
      China.
AB  - We examined the relationship between 2D:4D digit ratio and sexual orientation in
      men from China and analyzed the influences of the components used to assess
      sexual orientation and the criteria used to classify individuals as homosexual on
      this relationship. A total of 309 male and 110 female participants took part in a
      web-based survey. Our results showed that heterosexual men had a significantly
      lower 2D:4D than heterosexual women and exclusively homosexual men had a
      significantly higher left 2D:4D than heterosexual men whereas only exclusively
      homosexual men had a significantly higher right 2D:4D than heterosexual men when
      sexual orientation was assessed via sexual attraction. The left 2D:4D showed a
      significant positive correlation with sexual identity, sexual attraction, and
      sexual behavior, and the right 2D:4D showed a significant positive correlation
      with sexual attraction. The effect sizes for differences in 2D:4D between
      homosexual and heterosexual men varied according to criteria used to classify
      individuals as homosexual and sexual orientation components; the more stringent
      the criteria (scores closer to the homosexual category), the larger the effect
      sizes; further, sexual attraction yielded the largest effect size. There were no
      significant effects of age and latitude on Chinese 2D:4D. This study contributes
      to the current understanding of the relationship between 2D:4D and male sexual
      orientation.

PMID- 25957136
TI  - The Imperialism of Historical Arrogance: Where Is the Past in the DSM's Idea of
      Sexuality?
AB  - This article questions the historical awareness of the DSM-5 by investigating
      first the treatment of prostitution from the Victorian period to today as a means
      of medicalizing desire; and second, by looking at the category of hebephilia,
      where modern medicalizing classifications are criticized for ignoring ancient
      evidence. By this comparative method, the article shows how ignoring historical
      evidence allows the social and ideological elements in the work of defining
      psychological sexual diseases to remain concealed. 

PMID- 25957137
TI  - Reactive arthritis in relation to internal derangements of the temporomandibular
      joint: a case control study.
AB  - The aim of this study was to find out if reactive arthritis was involved in the
      aetiology of chronic closed lock of the temporomandibular joint (TMJ) by looking
      for bacterial antigens in the synovial membrane of the TMJ, and by studying the
      antibody serology and carriage of human leucocyte antigen (HLA) B27 in patients
      with chronic closed lock. Patients with reciprocal clicking and healthy subjects
      acted as controls. We studied a total of 43 consecutive patients, 15 with chronic
      closed lock, 13 with reciprocal clicking, and 15 healthy controls with no
      internal derangements of the TMJ. Venous blood samples were collected from all
      subjects for measurement of concentrations of HLA tissue antigen and serology
      against Chlamydia trachomatis, Yersinia enterocolitica, Salmonella spp.,
      Campylobacter jejuni, and Mycoplasma pneumoniae. Samples of synovial tissue from
      patients with closed lock and reciprocal clicking were obtained during discectomy
      and divided into two pieces, the first of which was tested by strand displacement
      amplification for the presence of C trachomatis, and the second of which was
      analysed for the presence of species-specific bacterial DNA using 16s rRNA pan
      polymerase chain reaction (PCR). There were no significant differences between
      the groups in the incidence of antibodies against M pneumoniae, Salmonella spp.
      or Y enterocolitica. No patient had antibodies towards C trachomatis or C jejuni.
      We found no bacterial DNA in the synovial fluid from any patient. The HLA B27
      antigen was present in 2/15 subjects in both the closed lock and control groups,
      and none in the reciprocal clicking group. In conclusion, reactive arthritis does
      not seem to be the mechanism of internal derangement of the TMJ. 

PMID- 25957138
TI  - Contrasted effects of natural complex mixtures of PAHs and metals on oxygen cycle
      in a microbial mat.
AB  - The contamination of polluted environments is often due to a complex mixture of
      pollutants sometimes at trace levels which nevertheless may have significant
      effects on the diversity and functioning of organisms. The aim of this study was
      to assess the functional responses of a microbial mat exposed to a natural
      complex mixture of PAHs and metals as a function of the maturation stage of the
      biofilm. Microbial mats sampled in a slightly polluted environment were exposed
      to contaminated water of a retention basin of an oil refinery. The responses of
      the microbial mats differed according to season. In spring 2012, strong
      inhibition of both oxygen production and respiration was observed relative to the
      control, with rates representing less than 5% of the control after 72 h of
      incubation. A decrease of microbial activities was followed by a decrease of the
      coupling between autotrophs and heterotrophs. In contrast, in autumn 2012, no
      significant changes for oxygen production and respiration were observed and the
      coupling between autotrophs and heterotrophs was not altered. The differences
      observed between the spring and autumn mats might be explained by the maturity of
      the microbial mat with dominance of heterotrophic bacteria in spring, and diatoms
      and cyanobacteria in autumn, as well as by the differences in the chemical
      composition of the complex mixture of PAHs and metals.

PMID- 25957139
TI  - Non-symbiotic N2-fixation and phosphate-solubility in Gangetic alluvial soil as
      influenced by pre-emergence herbicide residues.
AB  - An experiment has been conducted under laboratory conditions to investigate the
      effect of two pre-emergence herbicides viz., thiobencarb (at 1.5 and 4.5 kg a.i.
      ha(-1)) and pretilachlor (at 0.5 and 1.5 kg a.i. ha(-1)), on the changes of
      growth and activities of aerobic non-symbiotic N2-fixing bacteria and phosphate
      solubilizing microorganisms in relation to availability of mineral nitrogen and
      soluble phosphorus in the Gangetic alluvial soil (Typic Haplustept) of West
      Bengal, India. Application of herbicides, in general, significantly increased
      growth and activities of microorganisms, resulting in greater release of
      available nitrogen and soluble phosphorus in soil; and the stimulation was more
      pronounced when the herbicides were applied at their lower concentrations
      (recommended field application rates), more so with thiobencarb, as compared to
      pretilachlor. As compared to untreated control, application of thiobencarb at
      lower concentration increased the proliferation of aerobic non-symbiotic N2
      fixing bacteria, phosphate-solubilizing microorganisms and non-symbiotic N2
      fixing capacity of soil to the extent of 54.0, 44.6 and 31.7%, respectively; and
      accumulated the highest amount of available nitrogen (37.8%) and phosphorus
      (54.5%) in soil, while pretilachlor at field application rate highly induced
      (37.2%) phosphate-solubilizing capacity of soil. At higher concentration,
      pretilachlor was superior to thiobencarb in augmenting the growth and activities
      of phosphate-solubilizers. The results of the present study also indicated that
      gradual increase in concentration of the herbicides over their recommended field
      application rates was not much conducive for growth and activities of
      microorganisms, and subsequent release of nutrients in soil.

PMID- 25957140
TI  - Ecotoxicological assessment of cimetidine and determination of its potential for
      endocrine disruption using three test organisms: Daphnia magna, Moina macrocopa,
      and Danio rerio.
AB  - Cimetidine is a histamine H2-receptor antagonist used for treatment of
      gastrointestinal disorders. It is often detected in aquatic environments, but its
      ecotoxicological effects have not been well studied. Thus, ecotoxicity of
      cimetidine was evaluated using Daphnia magna and Moina macrocopa, and zebrafish
      (Danio rerio), and a predicted no effect concentration (PNEC) was derived. In D.
      magna, 48 h immobilization EC50 was determined at 394.9 mg L(-1). However,
      reproduction damages in D. magna were not found even at the maximum exposure
      level (30 mg L(-1)). For M. macrocopa, 48 h EC50 was found at 175.8 mg L(-1) and
      the 7 d reproduction no observed effect concentration (NOEC) was 1.1 mg L(-1).
      For D. rerio, 40 d growth NOEC was determined at 100 mg L(-1), the highest
      experimental concentration. The PNEC of cimetidine was estimated at 0.1 mg L(-1)
      based on M. macrocopa 7d reproduction NOEC. In 14 d adult zebrafish exposure,
      endocrine disruption potentials of cimetidine were observed. In male, decrease in
      plasma 17beta-estradiol and testosterone levels, up-regulation of gonadal cyp17,
      and down-regulation of hepatic eralpha were observed at 300 mg L(-1). In female,
      increase in plasma E2 level and down-regulation of hepatic cyp1a were noted at 3
      mg L(-1). Endocrine disruption effects were also observed in early life stage
      exposure. Up-regulation of erbeta at 17d, and cyp19a and vtg at 40 d post
      fertilization were detected at 100 mg L(-1), and co-occurrence of ovary and
      putative testis was observed at as low as 1.1 mg L(-1). The results indicate that
      there is little evidence for cimetidine to cause direct ecological impact at the
      current ambient levels in the aquatic environment. However potential consequences
      of endocrine disruption following long-term exposure in aquatic environment
      deserves further investigation.

PMID- 25957141
TI  - Silicon as neuroprotector or neurotoxic in the human neuroblastoma SH-SY5Y cell
      line.
AB  - Silicon (Si) is a trace element that has been considered to be an environmental
      contaminant for many years, although different studies have recently reported it
      is an essential element for living cells. The present study tested the ability of
      different concentrations of Si G57TM to induce neuroprotection or neurotoxicity
      over 24 h in the SH-SY5Y human neuroblastoma cell line. Cell viability, cellular
      proliferation, LDH release, ROS, antioxidant capacity, TBARS, caspase-3, -8 and 
      9, DNA fragmentation, and TNF-alpha levels were evaluated. Low Si doses (50-250
      ng mL(-1)) increased the cell viability and reduced caspase-3 and -8 activities
      and TNF-alpha level. The increase in cell viability was independent of any
      proliferative effect as there was no variation in cyclin E and PCNA levels. At
      higher concentrations, Si increased caspase-3, as well as TBARS, LDH, DNA
      fragmentation, and TNF-alpha releases. Altogether, these results suggest that Si
      could act either as a neuroprotector or a neurotoxic agent depending on the
      concentration tested. This study emphasizes the importance of developing new
      neuroprotective therapies based on low Si doses.

PMID- 25957142
TI  - Severe emphysematous pyelonephritis mimicking intestinal obstruction.
AB  - Emphysematous pyelonephritis is a severe necrotizing infection characterized by
      the presence of gas and/or fluid in the renal parenchyma, collecting system, or
      perirenal tissues. Emphysematous pyelonephritis with approximately 15 cm air
      fluid level, diffused ureteral involvement, and the accumulation of gas in liver
      and peritoneal cavity is very rare. Here, we reported a severe emphysematous
      pyelonephritis with multiple huge air-fluid level mimicking intestinal
      obstruction and with the accumulation of gas in liver and ureter in computed
      tomography imaging. The patient was successfully managed by percutaneous
      nephrostomy combined with medical treatment.

PMID- 25957143
TI  - Modified carotid sinus massage using an ultrasonography for maximizing vagal
      tone: a crossover simulation study.
AB  - INTRODUCTION: The aim of this study was to ascertain if a modified carotid sinus
      massage (CSM) using ultrasonography is superior to the conventional CSM for vagal
      tone generation. METHODS: This was a prospective, crossover, clinical trial
      including 30 subjects with sinus rhythm. Participants were paired, and they
      performed 2 types of CSM to each other. To perform the conventional technique,
      pressure was exerted at the point where the maximal impulse of the carotid pulse
      was palpated. In the modified technique, participants localized the point of
      maximal diameter just above the bifurcation of the common carotid artery using
      ultrasonography and applied pressure to that point. Mean differences between
      premaneuver and postmaneuver R-R intervals and heart rates were compared. The
      distance from the midline of the neck (x distance) to the angle of the mandible
      (y distance) was measured, and the mean distance between the 2 techniques was
      compared. RESULTS: The baseline mean premaneuver R-R interval and heart rate did
      not differ significantly between the 2 techniques. The postmaneuver R-R interval
      and heart rate as well as the mean R-R interval and heart rate differences were
      significantly greater in the modified CSM. The mean location determined using the
      modified CSM was located 0.8 cm lateral and 0.8 cm superior to the mean location
      of the conventional CSM. CONCLUSION: The modified CSM using ultrasonography might
      be more useful than the conventional CSM in reverting episodes of paroxysmal
      supraventricular tachycardia and may be a suitable alternative for treating the
      same in the emergency department.

PMID- 25957144
TI  - Prognosis of Critically ill patients in the ED and value of perfusion index
      measurement: a cross-sectional study.
AB  - OBJECTIVE: Critically ill patients have high mortality and admission rates
      requiring early recognition and a rapid management. In the present study, we
      evaluated the prognostic parameters in these patients and the value of perfusion
      index measurement as a novel tool for accomplishing emergency department (ED)
      triage. METHODS: Seven hundred seventy patients admitted to the critical care
      area of the ED in a month composed the study population. Perfusion index and
      vital signs (blood pressure, pulse rate, body temperature, pulse oximeter, and
      respiration rate) of the study patients were recorded to the study form. The
      communication data, admitting time, comorbidities, capillary refilling time, and
      blood gas analysis findings if obtained were recorded. Outcome of patients at the
      end of the ED period such as discharge, admission to the hospital, and death were
      also recorded. Outcome of patients at 15th and 30th days was identified by
      telephone call follow-up or from hospital records. RESULTS: Two hundred seventy
      eight patients (36.1%) were admitted to the hospital, 454 patients (59%) were
      discharged, 3 patients (0.4%) died in the ED, 25 patients (3.2%) were transferred
      to another hospital, and 10 patients (1.3%) refused treatment and left the ED.
      Sixty patients (7.8%), 39 (5.1%) of whom had died in 15 days' period, were dead
      at the end of 30-day follow-up period. Respiratory rate and pulse oximetry were
      significant parameters in hospital admission. Systolic blood pressure, diastolic
      blood pressure, pulse rate, respiratory rate, pulse oximetry, lactate levels in
      blood gas analysis, and ED length of stay were significant variables in 30-day
      mortality rate. Patients who were admitted to the hospital had higher rates of
      fever and diabetes. Patients who had died in the 30-day follow-up period had
      higher rates of diabetes and malignancy. In logistic regression analysis, the
      predictors of hospital admission were hypotension, fever, and pulse oximetry,
      whereas the predictors of 30-day mortality were systolic blood pressure,
      respiratory rate, pulse oximetry, and presence of malignancy. CONCLUSIONS:
      Perfusion index as a novel triage instrument was found to be an insignificant
      tool in predicting hospital admission and mortality of critically ill patients in
      the ED. However, diabetes and malignancy were found to be independent factors in
      determining the prognosis of these patients in addition to vital signs and should
      be considered by ED physicians either in triage field or inside the ED.

PMID- 25957145
TI  - Imaging utilization from the ED: no difference between observation and admitted
      patients.
AB  - OBJECTIVES: This study aims to determine the use of diagnostic imaging in
      emergency department (ED) observation units, particularly relative to inpatients
      admitted from the ED. STUDY DESIGN: Retrospective, descriptive analysis. METHODS:
      Our database of ED patients was retrospectively reviewed to identify patients
      managed in the observation unit or admitted to inpatient services. In February
      2014, we randomly selected 105 ED observation patients and 108 patients admitted
      to inpatient services from the ED. Electronic medical records were reviewed to
      assess diagnosis as well as type and quantity of imaging tests obtained. RESULTS:
      Eighty (76%) ED observation patients underwent imaging tests (radiographs, 39%;
      computed tomography, 25%; magnetic resonance imaging (MRI), 24%; ultrasound, 8%;
      other, 4%); 85 inpatients (79%) underwent imaging tests while in the ED
      (radiographs, 52%; computed tomography, 30%; MRI, 8%; ultrasound, 9%; other, 1%).
      There was no significant difference in overall imaging use between ED observation
      patients and inpatients, but ED observation patients were more likely to undergo
      MRI (P=.0243). The most common presenting diagnoses to the ED observation unit
      were neurologic complaints (25%), abdominal pain (17%), and cardiac symptoms
      (16%). CONCLUSION: There is no difference in the overall use of imaging in
      patients transferred to the ED observation unit vs those directly admitted from
      the ED. However, because ED observation unit patients tend to be accountable for
      a higher proportion of their health care bill, the impact of imaging in these
      patients is likely substantive.

PMID- 25957146
TI  - Use of extracorporeal membrane oxygenation in severe cardiac or respiratory
      failure.

PMID- 25957147
TI  - Description of procedures performed on patients by emergency medical services
      during mass casualty incidents in the United States.
AB  - BACKGROUND: Emergency medical services (EMS) preparedness is essential to reduce
      morbidity and mortality from mass casualty incidents (MCIs). OBJECTIVES: We
      sought to describe types and frequencies of common procedures performed during
      MCIs by EMS providers at different service levels. METHODS: This study was
      carried out using the 2012 US National EMS Public-Release Research Dataset
      maintained by the National Emergency Medical Services Information System.
      Emergency medical services activations coded as MCI at dispatch or by EMS
      personnel were included. The Center for Medicare and Medicaid Services service
      level was used for the level of service provided. A descriptive analysis
      characterizing the most common procedure types and frequencies by service level
      was carried out. RESULTS: Among the 19831189 EMS activations in the 2012 national
      data set, 53334 activations had an MCI code, of which 26110 activations were
      included. There were 8179 advanced life support (31.3%), 5811 basic life support
      (22.3%), 399 air medical transport (air transport fixed or rotary) (1.5%), and 38
      specialty care transport (0.2%) activations. A total of 107 different procedure
      types were reported. The most common procedures by procedure count were "spine
      immobilization" (21.8%) followed by "venous access extremity" (14.1%) and
      "assessment adult" (13.4%). A similar order was found for procedure frequencies
      by included EMS activations (24.1%, 19.3%, and 18.3%, respectively). Top 20
      procedures had different frequencies by levels of care except for "medical
      director control" (P = .19). CONCLUSIONS: Advanced EMS interventions are not
      frequent during MCIs in the United States. Emergency medical services systems
      with other types of providers or MCI response patterns might report different
      findings.

PMID- 25957148
TI  - Genomic redistribution of GR monomers and dimers mediates transcriptional
      response to exogenous glucocorticoid in vivo.
AB  - Glucocorticoids (GCs) are commonly prescribed drugs, but their anti-inflammatory
      benefits are mitigated by metabolic side effects. Their transcriptional effects,
      including tissue-specific gene activation and repression, are mediated by the
      glucocorticoid receptor (GR), which is known to bind as a homodimer to a
      palindromic DNA sequence. Using ChIP-exo in mouse liver under endogenous
      corticosterone exposure, we report here that monomeric GR interaction with a half
      site motif is more prevalent than homodimer binding. Monomers colocalize with
      lineage-determining transcription factors in both liver and primary macrophages,
      and the GR half-site motif drives transcription, suggesting that monomeric
      binding is fundamental to GR's tissue-specific functions. In response to
      exogenous GC in vivo, GR dimers assemble on chromatin near ligand-activated
      genes, concomitant with monomer evacuation of sites near repressed genes. Thus,
      pharmacological GCs mediate gene expression by favoring GR homodimer occupancy at
      classic palindromic sites at the expense of monomeric binding. The findings have
      important implications for improving therapies that target GR. 

PMID- 25957149
TI  - Expression of enterovirus 71 virus-like particles in transgenic enoki (Flammulina
      velutipes).
AB  - No commercial vaccines are currently available for enterovirus 71 (EV71)
      infection. Oral virus-like particle (VLP) vaccines are regarded as a better
      choice for prevention from food-borne diseases compared with injected whole virus
      vaccines. Unfortunately, the application of oral VLP vaccines produced from
      transgenic plants was limited due to the concerns of gene contamination.
      Alternatively, using transgenic mushrooms retains the advantages of transgenic
      plants and tremendously reduce risks of gene contamination. Polycistronic
      expression vectors harboring the glyceraldehyde-3-phospho-dehydrogenase promoter
      to codrive EV71 structural protein P1 and protease 3C using the 2A peptide of
      porcine teschovirus-1 were constructed and introduced into Flammulina velutipes
      via Agrobacterium tumefaciens-mediated transformation. The analyses of the
      genomic PCR, Southern blotting, and RT-PCR showed that the genes of P1 and 3C
      were integrated into the chromosomal DNA through a single insertion, and their
      resulting mRNAs were transcribed. The Western blotting analysis combined with LC
      MS/MS demonstrated that EV71 VLPs were composed of the four subunit proteins
      digested from P1 polyprotein by 3C protease. Through the use of a single particle
      electron microscope, images of 1705 particles with diameter similar to the EV71
      viron were used for 3D reconstruction. Protrusions were observed on the surface
      in the 2D class averages, and a 3D reconstruction of the VLPs was obtained. In
      conclusion, EV71 VLPs were successfully produced in transgenic F. velutipes using
      a polycistronic expression strategy, which indicates that this approach is
      promising for the development of oral vaccines produced in mushrooms. 

PMID- 25957150
TI  - Expression of bioactive anti-CD20 antibody fragments and induction of ER stress
      response in Arabidopsis seeds.
AB  - Seed-based expression system is an attractive platform for the production of
      recombinant proteins in molecular farming. Despite the many advantages of
      molecular farming, little is known about the effect of the different subcellular
      accumulation of recombinant proteins on the endoplasmic reticulum (ER) quality
      control system in host plants. In this study, we analyzed the expression of anti
      CD20 antibody fragments in seeds of Arabidopsis thaliana (ecotype Columbia) and
      corresponding glycosylation mutants, and evaluated the influence of three
      different signal sequences on the expression levels of scFv-Fc of C2B8. The
      highest protein accumulation level, with a maximum of 6.12 % total soluble
      proteins, was observed upon fusing proteins to the signal peptide of Arabidopsis
      seed storage albumin 2. The ER stress responses in developing seeds at 13 days
      post-anthesis were also compared across different transgenic lines under normal
      and heat shock conditions. Based on the gene expression profiles of ER stress
      transducers, our results suggest that accumulation of antibody fragments in the
      ER exerts more stress on ER homeostasis. In addition, quantitative PCR results
      also implicate enhanced activation of ER-associated degradation in transgenic
      lines. Last but not the least, we also demonstrate the anti-tumor potency of
      plant-derived proteins by showing the anti-tumor activity of purified scFv-Fc
      proteins against Daudi cells. Together, our data implies that better
      understanding of the interaction between exogenous protein production and the
      cellular quality control system of the host plant is necessary for the
      development of an optimal expression strategy that will be especially beneficial
      to commercial protein manufacturing.

PMID- 25957151
TI  - Unveiling characteristics of a bioelectrochemical system with polarity reversion
      for simultaneous azo dye treatment and bioelectricity generation.
AB  - A novel bioelectrochemical system (BES) operated with polarity reversion was
      explored for simultaneous anaerobic/aerobic treatment of azo dye and production
      of bioelectricity under extremely low buffer. The Congo red was first decolorized
      in anode, with completed color removal in 35 h. The resultant decolorization
      intermediates were then mineralized after the anode reversed to aerobic
      biocathode, evidenced by 55 % chemical oxygen demand (COD) removal in 200 h. The
      mineralization efficiency was further increased to 70 % when the period of the
      half-cycle was prolonged to 375 h. Meanwhile, the BES produced a continuous
      stable positive/negative alternate voltage output under 5 mM phosphate buffer
      because of the self-neutralization of the accumulated protons and hydroxyl ions
      in electrolyte. The electrode performance was significantly improved, which was
      indicated by alleviated electrode polarization, due to in situ use of accumulated
      protons and hydroxyl ions and enhanced electron transfer in the presence of Congo
      red and its degradation intermediates, which resulted in 1.05-fold increases in
      maximum power density (67.5 vs. 32.9 mW/m(2)). An analysis of the microbial
      diversity in the biofilm revealed that the biofilm was dominated by facultative
      bacteria with functional roles in contaminant degradation and electricity
      generation.

PMID- 25957152
TI  - Overexpression and characterization of a glucose-tolerant beta-glucosidase from
      T. aotearoense with high specific activity for cellobiose.
AB  - Thermoanaerobacterium aotearoense P8G3#4 produced beta-glucosidase (BGL)
      intracellularly when grown in liquid culture on cellobiose. The gene bgl,
      encoding beta-glucosidase, was cloned and sequenced. Analysis revealed that the
      bgl contained an open reading frame of 1314 bp encoding a protein of 446 amino
      acid residues, and the product belonged to the glycoside hydrolase family 1 with
      the canonical glycoside hydrolase family 1 (GH1) (beta/alpha)8 TIM barrel fold.
      Expression of pET-bgl together with a chaperone gene cloned in vector pGro7 in
      Escherichia coli dramatically enhanced the crude enzyme activity to a specific
      activity of 256.3 U/mg wet cells, which resulted in a 9.2-fold increase of that
      obtained from the expression without any chaperones. The purified BGL exhibited
      relatively high thermostability and pH stability with its highest activity at 60 
      degrees C and pH 6.0. In addition, the activities of BGL were remarkably
      stimulated by the addition of 5 mM Na(+) or K(+). The enzyme showed strong
      ability to hydrolyze cellobiose with a K m and V max of 25.45 mM and 740.5 U/mg,
      respectively. The BGL was activated by glucose at concentration varying from 50
      to 250 mM and tolerant to glucose inhibition with a K i of 800 mM glucose. The
      supplement of the purified BGL to the sugarcane bagasse hydrolysis mixture
      containing a commercial cellulase resulted in about 20 % enhancement of the
      released reducing sugars. These properties of the purified BGL should have
      important practical implication in its potential applications for better
      industrial production of glucose or bioethanol started from lignocellulosic
      biomass.

PMID- 25957154
TI  - Fruit peels support higher yield and superior quality bacterial cellulose
      production.
AB  - Fruit peels, also known as rinds or skins, are wastes readily available in large
      quantities. Here, we have used pineapple (PA) and watermelon (WM) peels as
      substrates in the culture media (containing 5 % sucrose and 0.7 % ammonium
      sulfate) for production of bacterial cellulose (BC). The bacterial culture used
      in the study, Komagataeibacter hansenii produced BC under static conditions as a
      pellicle at the air-liquid interface in standard Hestrin and Schramm (HS) medium.
      The yield obtained was ~3.0 g/100 ml (on a wet weight basis). The cellulosic
      nature of the pellicle was confirmed by CO2, H2O, N2, and SO2 (CHNS) analysis and
      Fourier transform infrared (FT-IR) spectroscopy. Scanning electron microscopy
      (SEM) and atomic force microscopy (AFM) of the pellicle revealed the presence of
      flat twisted ribbonlike fibrils (70-130 nm wide). X-ray diffraction analysis
      proved its crystalline nature (matching cellulose I) with a crystallinity index
      of 67 %. When K. hansenii was grown in PA and WM media, BC yields were threefolds
      or fourfolds higher than those obtained in HS medium. Interestingly, textural
      characterization tests (viz., SEM, crystallinity index, resilience, hardness,
      adhesiveness, cohesiveness, springiness, shear energy and stress, and energy
      required for puncturing the pellicle) proved that the quality of BC produced in
      PA and WM media was superior to the BC produced in HS medium. These findings
      demonstrate the utility of the newly designed media for getting higher yields and
      better quality of BC, which could make fermentative production of BC more
      attractive on a commercial scale.

PMID- 25957153
TI  - The production of omega-hydroxy palmitic acid using fatty acid metabolism and
      cofactor optimization in Escherichia coli.
AB  - Hydroxylated fatty acids (HFAs) are used as important precursors for bulk and
      fine chemicals in the chemical industry. Here, to overproduce long-chain (C16
      C18) fatty acids and hydroxy fatty acid, their biosynthetic pathways including
      thioesterase (Lreu_0335) from Lactobacillus reuteri DSM20016, beta-hydroxyacyl
      ACP dehydratase (fabZ) from Escherichia coli, and a P450 system (i.e., CYP153A
      from Marinobacter aquaeolei VT8 and camA/camB from Pseudomonas putida ATCC17453)
      were overexpressed. Acyl-CoA synthase (fadD) involved in fatty acid degradation
      by beta-oxidation was also deleted in E. coli BW25113. The engineered E. coli
      FFA4 strain without the P450 system could produce 503.0 mg/l of palmitic (C16)
      and 508.4 mg/l of stearic (C18) acids, of which the amounts are ca. 1.6- and 2.3
      fold higher than those of the wild type. On the other hand, the E. coli HFA4
      strain including the P450 system for omega-hydroxylation could produce 211.7 mg/l
      of omega-hydroxy palmitic acid, which was 42.1 +/- 0.1 % of the generated
      palmitic acid, indicating that the hydroxylation reaction was the rate
      determining step for the HFA production. For the maximum production of omega
      hydroxy palmitic acid, NADH, i.e., an essential cofactor for P450 reaction, was
      overproduced by the integration of NAD(+)-dependent formate dehydrogenase (FDH)
      from Candida boidinii into E. coli chromosome and the deletion of alcohol
      dehydrogenase (ADH). Finally, the NADH-level-optimized E. coli strain produced
      610 mg/l of omega-hydroxy palmitic acid (omega-HPA), which was almost a threefold
      increase in its yield compared to the same strain without NADH overproduction.

PMID- 25957155
TI  - Unexploited potential of some biotechnological techniques for biofertilizer
      production and formulation.
AB  - The massive application of chemical fertilizers to support crop production has
      resulted in soil, water, and air pollution at a global scale. In the same time,
      this situation escalated consumers' concerns regarding quality and safety of food
      production which, due to increase of fertilizer prices, have provoked
      corresponding price increase of food products. It is widely accepted that the
      only solution is to boost exploitation of plant-beneficial microorganisms which
      in conditions of undisturbed soils play a key role in increasing the availability
      of minerals that otherwise are inaccessible to plants. This review paper is
      focused on the employment of microbial inoculants and their production and
      formulation. Special attention is given to biotechniques that are not fully
      exploited as tools for biofertilizer manufacturing such as microbial co
      cultivation and co-immobilization. Another emerging area includes
      biotechnological production and combined usage of microorganisms/active natural
      compounds (biostimulants) such as plant extracts and exudates, compost extracts,
      and products like strigolactones, which improve not only plant growth and
      development but also plant-microbial interactions. The most important potential
      and novel strategies in this field are presented as well as the tendencies that
      will be developed in the near future.

PMID- 25957156
TI  - Drug use and childhood-, military- and post-military trauma exposure among women
      and men veterans.
AB  - BACKGROUND: The current study was undertaken to examine whether posttraumatic
      stress symptoms (PTSS) and depressive symptoms mediated the association between
      trauma exposure (combat-related trauma and non-combat traumas occurring before,
      during, and after military service), and drug abuse symptoms use among male and
      female veterans. METHODS: Participants were 2304 (1851 male, 453 female) veterans
      who took part in a multi-site research study conducted through the Department of
      Veterans Affairs Mid-Atlantic Mental Illness Research, Education and Clinical
      Center (VISN 6 MIRECC). Path analytic models were used to determine the
      association between problematic past-year drug use and combat-related and non
      combat trauma experienced before, during, or after the military and whether
      current post-traumatic stress symptoms or depressive symptoms mediated these
      associations. RESULTS: For both male and female veterans, depressive symptoms
      significantly mediated the effects of pre- and post-military trauma on drug abuse
      symptoms. CONCLUSION: Mental health providers who work with trauma-exposed Iraq
      and Afghanistan era veterans should assess for drug use, depressive symptoms, and
      life-span trauma (i.e., not only combat-related traumas) as part of a thorough
      trauma-based assessment for both men and women.

PMID- 25957158
TI  - The vaginal and gastrointestinal microbiomes in gynecologic cancers: a review of
      applications in etiology, symptoms and treatment.
AB  - The human microbiome is the collection of microorganisms in the body that exist
      in a mutualistic relationship with the host. Recent studies indicate that
      perturbations in the microbiome may be implicated in a number of diseases,
      including cancer. More specifically, changes in the gut and vaginal microbiomes
      may be associated with a variety of gynecologic cancers, including cervical
      cancer, uterine cancer, and ovarian cancer. Current research and gaps in
      knowledge regarding the association between the gut and vaginal microbiomes and
      the development, progression, and treatment of gynecologic cancers are reviewed
      here. In addition, the potential use of probiotics to manage symptoms of these
      gynecologic cancers is discussed. A better understanding of how the microbiome
      composition is altered at these sites and its interaction with the host may aid
      in prevention, optimization of current therapies, development of new therapeutic
      agents and/or dosing regimens, and possibly limit the side effects associated
      with cancer treatment.

PMID- 25957159
TI  - Ivermectin binds to Haemonchus contortus tubulins and promotes stability of
      microtubules.
AB  - Haemonchus contortus is a nematode of livestock that can cause severe disease and
      mortality. Ivermectin, an anti-parasitic drug that targets glutamate-gated
      chloride channels, is widely used in humans, livestock, companion animals and
      agriculture. Although an association between genetic changes to beta-tubulin and
      exposure to ivermectin has been previously reported, direct binding between
      ivermectin and tubulin has not been demonstrated to date. Tubulin/microtubules
      are key targets for many anti-mitotic drugs used in anti-parasite and cancer
      therapies. We now report that ivermectin exposure increased the rate and extent
      of polymerisation of H. contortus recombinant alpha- and beta-tubulin, and
      protected the parasitic alpha- and beta-tubulins from limited trypsin
      proteolysis. Direct binding between ivermectin and the tubulin monomers exhibited
      low micromolar affinities, as determined using surface plasmon resonance.
      Subsequent equilibrium dialysis indicated that ivermectin and Taxol compete for
      binding to tubulin, supporting our molecular modelling that predicts ivermectin
      interacts with the Taxol binding pocket of both parasitic and mammalian tubulins.
      Collectively, our data indicate that ivermectin can bind to and stabilise
      microtubules (i.e., alter the tubulin polymerisation equilibrium) and this can
      then lead to mitotic arrest. This work extends the range of known pharmacological
      effects of ivermectin, and reveals its potential as an anti-mitotic agent.

PMID- 25957157
TI  - Non-smoker exposure to secondhand cannabis smoke II: Effect of room ventilation
      on the physiological, subjective, and behavioral/cognitive effects.
AB  - INTRODUCTION: Cannabis is the most widely used illicit drug. Many individuals are
      incidentally exposed to secondhand cannabis smoke, but little is known about the
      effects of this exposure. This report examines the physiological, subjective, and
      behavioral/cognitive effects of secondhand cannabis exposure, and the influence
      of room ventilation on these effects. METHODS: Non-cannabis-using individuals
      were exposed to secondhand cannabis smoke from six individuals smoking cannabis
      (11.3% THC) ad libitum in a specially constructed chamber for 1h. Chamber
      ventilation was experimentally manipulated so that participants were exposed
      under unventilated conditions or with ventilation at a rate of 11 air
      exchanges/h. Physiological, subjective and behavioral/cognitive measures of
      cannabis exposure assessed after exposure sessions were compared to baseline
      measures. RESULTS: Exposure to secondhand cannabis smoke under unventilated
      conditions produced detectable cannabinoid levels in blood and urine, minor
      increases in heart rate, mild to moderate self-reported sedative drug effects,
      and impaired performance on the digit symbol substitution task (DSST). One urine
      specimen tested positive at using a 50 ng/ml cut-off and several specimens were
      positive at 20 ng/ml. Exposure under ventilated conditions resulted in much lower
      blood cannabinoid levels, and did not produce sedative drug effects, impairments
      in performance, or positive urine screen results. CONCLUSIONS: Room ventilation
      has a pronounced effect on exposure to secondhand cannabis smoke. Under extreme,
      unventilated conditions, secondhand cannabis smoke exposure can produce
      detectable levels of THC in blood and urine, minor physiological and subjective
      drug effects, and minor impairment on a task requiring psychomotor ability and
      working memory.

PMID- 25957160
TI  - Evolution of seasonal transmission patterns in avian blood-borne parasites.
AB  - In temperate regions, many vector-borne parasites maximise their transmission
      prospects by adjusting reproduction to seasonal cycles of host susceptibility and
      vector availability. Nevertheless, in these regions there are areas where
      environmental conditions are favourable throughout the year, so that parasites
      could benefit from a year-round transmission strategy. We analysed how different
      transmission strategies (strict summer transmission, extended summer transmission
      - including spring and autumn, and year round transmission) have evolved among
      the different genetic lineages of Haemoproteus parabelopolskyi, an avian blood
      borne parasite shared by three sibling species of passerine hosts. Our results
      indicate that the ancestral state of this clade of parasites had a strict summer
      transmission with the blackcap (Sylvia atricapilla) as the host. Other
      transmission strategies and switches to the other host species (Sylvia abyssinica
      and Sylvia borin) evolved recently, several times, independently. This suggests
      that, although year-round transmission is ecologically successful at present,
      seasonal transmission may have become more stable over evolutionary time.
      Switches from strict summer to an extended or year-round transmission strategy
      could have ecological consequences, if they promote the spread of parasites into
      more distant regions, transported by the migrating bird hosts. Therefore, a
      deeper knowledge of how different parasite transmission strategies are structured
      among birds in temperate areas is essential for understanding how disease
      emergence risks may develop in the future. 

PMID- 25957162
TI  - Educational trajectories after childhood cancer: When illness experience matters.
AB  - With the increase in survival from childhood cancer, research has increasingly
      focused on the educational and professional achievements of childhood cancer
      survivors. Yet, if large-scale studies provide an acute description of the
      current situation of childhood cancer survivors, little is known about their
      trajectories and the social processes shaping these trajectories. Using a
      qualitative methodology, drawing from a life course perspective, this study
      sought to describe the role of childhood cancer and its side effects in
      educational trajectories, as perceived by the participants. We investigated
      related processes of social adjustment to cancer, that is to say, choices or
      decisions that survivors related to the illness in the making of their career
      plans. Eighty long-term French childhood cancer survivors participating in the
      Euro2K longitudinal study were interviewed through in-depth, face-to-face
      interviews undertaken in 2011-2012. There were various types of impact described
      by respondents of the diagnosis of cancer on their trajectories. These varied
      according to gender. In women, childhood cancer tended to result in poor
      educational achievement, or in steering the individual towards a health care or
      child care occupation. This was justified by a desire to return the support that
      had been offered to them as patients. In men, however, childhood cancer led to a
      shift in career plans, because of physical sequelae, or because of concerns about
      their future health. Paradoxically, this limitation had a positive impact in
      their occupational achievement, as most of these men disregarded blue-collar jobs
      and chose more qualified white-collar occupations. Overall, findings suggest that
      childhood cancer influenced educational trajectories and, thus, socioeconomic
      status in adulthood, through mechanisms embedded in gender norms. These
      mechanisms could explain gender inequalities in educational achievement after
      childhood cancer reported in large-scale cohort studies. 

PMID- 25957161
TI  - Conserved Amblyomma americanum tick Serpin19, an inhibitor of blood clotting
      factors Xa and XIa, trypsin and plasmin, has anti-haemostatic functions.
AB  - Tick saliva serine protease inhibitors (serpins) facilitate tick blood meal
      feeding through inhibition of protease mediators of host defense pathways. We
      previously identified a highly conserved Amblyomma americanum serpin 19 that is
      characterised by its reactive center loop being 100% conserved in ixodid ticks.
      In this study, biochemical characterisation reveals that the ubiquitously
      transcribed A. americanum serpin 19 is an anti-coagulant protein, inhibiting the
      activity of five of the eight serine protease blood clotting factors. Pichia
      pastoris-expressed recombinant (r) A. americanum serpin 19 inhibits the enzyme
      activity of trypsin, plasmin and blood clotting factors (f) Xa and XIa, with
      stoichiometry of inhibition estimated at 5.1, 9.4, 23.8 and 28, respectively.
      Similar to typical inhibitory serpins, recombinant A. americanum serpin 19 forms
      irreversible complexes with trypsin, fXa and fXIa. At a higher molar excess of
      recombinant A. americanum serpin 19, fXIIa is inhibited by 82.5%, and thrombin
      (fIIa), fIXa, chymotrypsin and tryptase are inhibited moderately by 14-29%. In
      anti-hemostatic functional assays, recombinant A. americanum serpin 19 inhibits
      thrombin but not ADP and cathepsin G activated platelet aggregation, delays
      clotting in recalcification and thrombin time assays by up to 250s, and up to 40s
      in the activated partial thromboplastin time assay. Given A. americanum serpin 19
      high cross-tick species conservation, and specific reactivity of recombinant A.
      americanum serpin 19 with antibodies to A. americanum tick saliva proteins, we
      conclude that recombinant A. americanum serpin 19 is a potential candidate for
      development of a universal tick vaccine. 

PMID- 25957163
TI  - Access to critical medicines: When are compulsory licenses effective in price
      negotiations?
AB  - Governments of developing countries can be in a vulnerable position with respect
      to patent protected drugs supplied by foreign firms, if the technology cannot be
      licensed or independently developed by local firms. In such instances, one
      possible solution is to negotiate for a price-drop with the patent holder in lieu
      of issuing a compulsory license. The present paper develops a game theoretic
      model of such bargaining and shows that while compulsory licenses do not occur
      under complete information, they can be issued under incomplete information. The
      model is tested against real episodes of compulsory licenses to derive policy
      insight. 

PMID- 25957164
TI  - Validation of a nurses' views on electronic medical record systems (EMR)
      questionnaire in Turkish health system.
AB  - Using of EMR in health services and organizations is steadily increasing for
      quality improvement, cost effectiveness and performance development. However, no
      validated national and international instruments (scale, questionnaire, index,
      and inventory) have assessed the effectiveness, satisfaction, health care
      savings, patient safety and cost minimization of electronic medical and health
      systems from the viewpoint and perceptions of nurses in Turkish health services.
      The perceptions of health care professionals especially physicians and nurses can
      contribute important information that may predict their acceptance of EMR and
      desired mode of use for EMR, evaluation performance of EMR thus guiding EMR
      implementation in hospitals. This article is a report of validation of the
      instrument to measure nurses' views on the use, quality and user satisfaction
      with EMR in Turkish health system. Items in the questionnaire were designed and
      obtained following O.G. Otieno, H. Toyama, M. Asonuma, M. Kanai-Pak, K. Naitoh's
      questionnaire about Use, Quality and User Satisfaction with EMR systems.
      Reliability and validity were examined and investigated in terms of responses
      from 487 nurses from one education hospital in Ankara, Turkey. This study was
      planned and conducted at a university hospital. The validation process was based
      on construct validity in this study. The response rate was 74.92%. Cronbach's
      alphas of three factors (use, quality and satisfaction of EMR) ranged from 0.78
      to 0.94. Goodness-of-fit indices from the confirmatory factor analysis showed a
      reasonable model fit. Results of confirmatory factor analysis showed that chi2
      statistic indicated significant result (p < 0.001) and model fit was acceptable
      according to relative chi2 statistic (chi2/df = 2.8 < 5). Further validation of
      the instrument could yield positive results in health systems in the different
      countries. Also further validation and reliability studies could be planned on
      physicians and other health professionals.

PMID- 25957165
TI  - Real-time feedback for improving compliance to hand sanitization among healthcare
      workers in an open layout ICU using radiofrequency identification.
AB  - The aim of this study is to increase hand sanitizer usage among healthcare
      workers by developing and implementing a low-cost intervention using RFID and
      wireless mesh networks to provide real-time alarms for increasing hand hygiene
      compliance during opportune moments in an open layout Intensive Care Unit (ICU).
      A wireless, RFID based system was developed and implemented in the ICU. The ICU
      beds were divded into an intervention arm (n = 10) and a control arm (n = 14).
      Passive RFID tags were issued to the doctors, nurses and support staff of the
      ICU. Long range RFID readers were positioned strategically. Sensors were placed
      beneath the hand sanitizers to record sanitizer usage. The system would alert the
      HCWs by flashing a light if an opportune moment for hand sanitization was
      detected. A significant increase in hand sanitizer use was noted in the
      intervention arm. Usage was highest during the early part of the workday and
      decreased as the day progressed. Hand wash events per person hour was highest
      among the ancilliary staff followed by the doctors and nurses. Real-time feedback
      has potential to increase hand hygiene compliance among HCWs. The system
      demonstrates the possibility of automating compliance monitoring in an ICU with
      an open layout. 

PMID- 25957166
TI  - Batf2/Irf1 induces inflammatory responses in classically activated macrophages,
      lipopolysaccharides, and mycobacterial infection.
AB  - Basic leucine zipper transcription factor Batf2 is poorly described, whereas Batf
      and Batf3 have been shown to play essential roles in dendritic cell, T cell, and
      B cell development and regulation. Batf2 was drastically induced in IFN-gamma
      activated classical macrophages (M1) compared with unstimulated or IL-4-activated
      alternative macrophages (M2). Batf2 knockdown experiments from IFN-gamma
      activated macrophages and subsequent expression profiling demonstrated important
      roles for regulation of immune responses, inducing inflammatory and host
      protective genes Tnf, Ccl5, and Nos2. Mycobacterium tuberculosis (Beijing strain
      HN878)-infected macrophages further induced Batf2 and augmented host-protective
      Batf2-dependent genes, particularly in M1, whose mechanism was suggested to be
      mediated through both TLR2 and TLR4 by LPS and heat-killed HN878 (HKTB)
      stimulation experiments. Irf1 binding motif was enriched in the promoters of
      Batf2-regulated genes. Coimmunoprecipitation study demonstrated Batf2 association
      with Irf1. Furthermore, Irf1 knockdown showed downregulation of IFN-gamma- or
      LPS/HKTB-activated host-protective genes Tnf, Ccl5, Il12b, and Nos2.
      Conclusively, Batf2 is an activation marker gene for M1 involved in gene
      regulation of IFN-gamma-activated classical macrophages, as well as LPS/HKTB
      induced macrophage stimulation, possibly by Batf2/Irf1 gene induction. Taken
      together, these results underline the role of Batf2/Irf1 in inducing inflammatory
      responses in M. tuberculosis infection.

PMID- 25957167
TI  - Generation of TCR-engineered T cells and their use to control the performance of
      T cell assays.
AB  - The systematic assessment of the human immune system bears huge potential to
      guide rational development of novel immunotherapies and clinical decision making.
      Multiple assays to monitor the quantity, phenotype, and function of Ag-specific T
      cells are commonly used to unravel patients' immune signatures in various disease
      settings and during therapeutic interventions. When compared with tests measuring
      soluble analytes, cellular immune assays have a higher variation, which is a
      major technical factor limiting their broad adoption in clinical immunology. The
      key solution may arise from continuous control of assay performance using TCR
      engineered reference samples. We developed a simple, stable, robust, and scalable
      technology to generate reference samples that contain defined numbers of
      functional Ag-specific T cells. First, we show that RNA-engineered lymphocytes,
      equipped with selected TCRs, can repetitively deliver functional readouts of a
      controlled size across multiple assay platforms. We further describe a concept
      for the application of TCR-engineered reference samples to keep assay performance
      within or across institutions under tight control. Finally, we provide evidence
      that these novel control reagents can sensitively detect assay variation
      resulting from typical sources of error, such as low cell quality, loss of
      reagent stability, suboptimal hardware settings, or inaccurate gating. 

PMID- 25957168
TI  - Thymic involution perturbs negative selection leading to autoreactive T cells
      that induce chronic inflammation.
AB  - Thymic involution and the subsequent amplified release of autoreactive T cells
      increase the susceptibility toward developing autoimmunity, but whether they
      induce chronic inflammation with advanced age remains unclear. The presence of
      chronic low-level proinflammatory factors in elderly individuals (termed
      inflammaging) is a significant risk factor for morbidity and mortality in
      virtually every chronic age-related disease. To determine how thymic involution
      leads to the persistent release and activation of autoreactive T cells capable of
      inducing inflammaging, we used a Foxn1 conditional knockout mouse model that
      induces accelerated thymic involution while maintaining a young periphery. We
      found that thymic involution leads to T cell activation shortly after thymic
      egress, which is accompanied by a chronic inflammatory phenotype consisting of
      cellular infiltration into non-lymphoid tissues, increased TNF-alpha production,
      and elevated serum IL-6. Autoreactive T cell clones were detected in the
      periphery of Foxn1 conditional knockout mice. A failure of negative selection,
      facilitated by decreased expression of Aire rather than impaired regulatory T
      cell generation, led to autoreactive T cell generation. Furthermore, the young
      environment can reverse age-related regulatory T cell accumulation in naturally
      aged mice, but not inflammatory infiltration. Taken together, these findings
      identify thymic involution and the persistent activation of autoreactive T cells
      as a contributing source of chronic inflammation (inflammaging).

PMID- 25957169
TI  - Genetic variation in SP-A2 leads to differential binding to Mycoplasma pneumoniae
      membranes and regulation of host responses.
AB  - Mycoplasma pneumoniae is an extracellular pathogen that colonizes mucosal
      surfaces of the respiratory tract and is associated with asthma exacerbations.
      Previous reports demonstrate that surfactant protein-A (SP-A) binds live M.
      pneumoniae and mycoplasma membrane fractions (MMF) with high affinity. Humans
      express a repertoire of single-amino acid genetic variants of SP-A that may be
      associated with lung disease, and our findings demonstrate that allelic
      differences in SP-A2 (Gln223Lys) affect the binding to MMF. We show that SP-A(-/
      ) mice are more susceptible to MMF exposure and have significant increases in
      mucin production and neutrophil recruitment. Novel humanized SP-A2-transgenic
      mice harboring the hSP-A2 223K allele exhibit reduced neutrophil influx and mucin
      production in the lungs when challenged with MMF compared with SP-A(-/-) mice.
      Conversely, mice expressing hSP-A2 223Q have increased neutrophil influx and
      mucin production that are similar to SP-A(-/-) mice. Using tracheal epithelial
      cell cultures, we show that enhanced mucin production to MMF occurs in the
      absence of SP-A and is not dependent upon neutrophil recruitment. Increased
      phosphorylation of the epidermal growth factor receptor (EGFR) was evident in the
      lungs of MMF-challenged mice when SP-A was absent. Pharmacologic inhibition of
      EGFR prior to MMF challenge dramatically reduced mucin production in SP-A(-/-)
      mice. These findings suggest a protective role for SP-A in limiting MMF
      stimulated mucin production that occurs through interference with EGFR-mediated
      signaling. SP-A interaction with the EGFR signaling pathway appears to occur in
      an allele-specific manner that may have important implications for SP-A
      polymorphisms in human diseases.

PMID- 25957170
TI  - Cutting edge: T follicular helper cell differentiation is defective in the
      absence of Bcl6 BTB repressor domain function.
AB  - T follicular helper (Tfh) cells are essential for germinal centers (GCs) and most
      long-term humoral immunity. Differentiation of Tfh cells depends on the
      transcriptional repressor B cell CLL/lymphoma 6 (Bcl6). Bcl6 mediates gene
      repression via the recruitment of corepressors. Currently, it is unknown how Bcl6
      recruits corepressors to regulate gene expression of Tfh cells. In this article,
      we demonstrate, using a mutant form of Bcl6 with two BTB (bric-a-brac, tramtrack,
      broad-complex) mutations that abrogate corepressor binding, that the Bcl6 BTB
      domain is required for proper differentiation of Tfh and GC-Tfh cells in vivo.
      Importantly, we also observe a significant defect in GC B cell development. These
      results are consistent in multiple contexts, including a novel lymphocytic
      choriomeningitis virus nucleoprotein-specific TCR-transgenic mouse model. Taken
      together, these data suggest that the Bcl6 BTB domain is a key mediator of the
      differentiation of Tfh cells.

PMID- 25957172
TI  - Quantitative profiling of immune repertoires for minor lymphocyte counts using
      unique molecular identifiers.
AB  - Emerging high-throughput sequencing methods for the analyses of complex structure
      of TCR and BCR repertoires give a powerful impulse to adaptive immunity studies.
      However, there are still essential technical obstacles for performing a truly
      quantitative analysis. Specifically, it remains challenging to obtain
      comprehensive information on the clonal composition of small lymphocyte
      populations, such as Ag-specific, functional, or tissue-resident cell subsets
      isolated by sorting, microdissection, or fine needle aspirates. In this study, we
      report a robust approach based on unique molecular identifiers that allows
      profiling Ag receptors for several hundred to thousand lymphocytes while
      preserving qualitative and quantitative information on clonal composition of the
      sample. We also describe several general features regarding the data analysis
      with unique molecular identifiers that are critical for accurate counting of
      starting molecules in high-throughput sequencing applications.

PMID- 25957171
TI  - Neonatal exposure to pneumococcal phosphorylcholine modulates the development of
      house dust mite allergy during adult life.
AB  - Currently, ~20% of the global population suffers from an allergic disorder.
      Allergies and asthma occur at higher rates in developed and industrialized
      countries. It is clear that many human atopic diseases are initiated neonatally
      and herald more severe IgE-mediated disorders, including allergic asthma, which
      is driven by the priming of Th2 effector T cells. The hygiene hypothesis attempts
      to link the increased excessively sanitary conditions early in life to a default
      Th2 response and increasing allergic phenomena. Despite the substantial
      involvement of IgE Abs in such conditions, little attention has been paid to the
      effects of early microbial exposure on the B cell repertoire prior to the
      initiation of these diseases. In this study, we use Ab-binding assays to
      demonstrate that Streptococcus pneumoniae and house dust mite (HDM) bear similar
      phosphorylcholine (PC) epitopes. Neonatal C57BL/6 mice immunized with a PC
      bearing pneumococcal vaccine expressed increased frequencies of PC-specific B
      cells in the lungs following sensitizing exposure to HDM as adults. Anti-PC IgM
      Abs in the lung decreased the interaction of HDM with pulmonary APCs and were
      affiliated with lowered allergy-associated cell infiltration into the lung, IgE
      production, development of airway hyperresponsiveness, and Th2 T cell priming.
      Thus, exposure of neonatal mice to PC-bearing pneumococci significantly reduced
      the development of HDM-induced allergic disease during adult life. Our findings
      demonstrate that B cells generated against conserved epitopes expressed by
      bacteria, encountered early in life, are also protective against the development
      of allergic disease during adult life.

PMID- 25957173
TI  - GPs role identifying young people who self-harm: a mixed methods study.
AB  - BACKGROUND: Self-harm is common among young people and is evident in increasingly
      younger age groups. Many young people who self-harm do visit their GP but do not
      access specialist support. GP's can find it challenging to raise and discuss this
      sensitive subject with young people during short consultations. OBJECTIVE: To
      explore GP's capabilities, motivations and opportunities for discussing self-harm
      and to identify barriers to and enablers for proactively discussing self-harm
      with young people. DESIGN AND SETTING: An exploratory, mixed methods study was
      designed comprising an online survey and a qualitative interview study with GPs
      in the South West of England. METHODS: An online survey was completed by 28 GPs.
      Ten GPs took part by telephone, in semi-structured interviews. Quantitative data
      was analysed using descriptive statistical techniques and thematic analysis was
      used to analyse the qualitative data. Findings from the quantitative and
      qualitative analysis are synthesized to illustrate GPs' skills, knowledge and
      perceptions about young people who self-harm. RESULTS: Experienced GPs may
      underestimate the prevalence of self-harm in young people, particularly in the 11
      14 age range. While consultations with young people and their carers can be
      challenging, GPs acknowledge that it is their role to provide support for young
      people who self-harm. GPs would welcome training for themselves and other
      practice staff in talking to young people and practical information about self
      harm. CONCLUSION: All primary care staff who provide frontline support to young
      people should receive education and practical training in talking about self
      harm.

PMID- 25957175
TI  - Modeling of the OX1R-orexin-A complex suggests two alternative binding modes.
AB  - BACKGROUND: Interactions between the orexin peptides and their cognate OX1 and
      OX2 receptors remain poorly characterized. Site-directed mutagenesis studies on
      orexin peptides and receptors have indicated amino acids important for ligand
      binding and receptor activation. However, a better understanding of specific
      pairwise interactions would benefit small molecule discovery. RESULTS: We
      constructed a set of three-dimensional models of the orexin 1 receptor based on
      the 3D-structures of the orexin 2 receptor (released while this manuscript was
      under review), neurotensin receptor 1 and chemokine receptor CXCR4, conducted an
      exhaustive docking of orexin-A16-33 peptide fragment with ZDOCK and RDOCK, and
      analyzed a total of 4301 complexes through multidimensional scaling and
      clustering. The best docking poses reveal two alternative binding modes, where
      the C-terminus of the peptide lies deep in the binding pocket, on average about 5
      6 A above Tyr(6.48) and close to Gln(3.32). The binding modes differ in the about
      100 degrees  rotation of the peptide; the peptide His26 faces either the
      receptor's fifth transmembrane helix or the seventh helix. Both binding modes are
      well in line with previous mutation studies and partake in hydrogen bonding
      similar to suvorexant. CONCLUSIONS: We present two binding modes for orexin-A
      into orexin 1 receptor, which help rationalize previous results from site
      directed mutagenesis studies. The binding modes should serve small molecule
      discovery, and offer insights into the mechanism of receptor activation.

PMID- 25957176
TI  - Response of a polymer network to the motion of a rigid sphere.
AB  - In view of recent microrheology experiments we re-examine the problem of a rigid
      sphere oscillating inside a dilute polymer network. The network and its solvent
      are treated using the two-fluid model. We show that the dynamics of the medium
      can be decomposed into two independent incompressible flows. The first, dominant
      at large distances and obeying the Stokes equation, corresponds to the collective
      flow of the two components as a whole. The other, governing the dynamics over an
      intermediate range of distances and following the Brinkman equation, describes
      the flow of the network and solvent relative to one another. The crossover
      between these two regions occurs at a dynamic length scale which is much larger
      than the network's mesh size. The analysis focuses on the spatial structure of
      the medium's response and the role played by the dynamic crossover length. We
      examine different boundary conditions at the sphere surface. The large-distance
      collective flow is shown to be independent of boundary conditions and network
      compressibility, establishing the robustness of two-point microrheology at large
      separations. The boundary conditions that fit the experimental results for inert
      spheres in entangled F-actin networks are those of a free network, which does not
      interact directly with the sphere. Closed-form expressions and scaling relations
      are derived, allowing for the extraction of material parameters from a
      combination of one- and two-point microrheology. We discuss a basic deficiency of
      the two-fluid model and a way to bypass it when analyzing microrheological data. 

PMID- 25957177
TI  - The nematode C. elegans as a complex viscoelastic fluid.
AB  - The viscoelastic material properties of the model organism C. elegans were probed
      with a micropipette deflection technique and modelled with the standard linear
      solid model. Dynamic relaxation measurements were performed on the millimetric
      nematode to investigate its viscous characteristics in detail. We show that the
      internal properties of C. elegans can not be fully described by a simple
      Newtonian fluid. Instead, a power-law fluid model was implemented and shown to be
      in excellent agreement with experimental results. The nematode exhibits shear
      thinning properties and its complex fluid characteristics were quantified. The
      bending-rate dependence of the internal damping coefficient of C. elegans could
      affect its gait modulation in different external environments. 

PMID- 25957174
TI  - Sodium channel Nav1.7 in vascular myocytes, endothelium, and innervating axons in
      human skin.
AB  - BACKGROUND: The skin is a morphologically complex organ that serves multiple
      complementary functions, including an important role in thermoregulation, which
      is mediated by a rich vasculature that is innervated by sympathetic and sensory
      endings. Two autosomal dominant disorders characterized by episodes of severe
      pain, inherited erythromelalgia (IEM) and paroxysmal extreme pain disorder (PEPD)
      have been directly linked to mutations that enhance the function of sodium
      channel Nav1.7. Pain attacks are accompanied by reddening of the skin in both
      disorders. Nav1.7 is known to be expressed at relatively high levels within both
      dorsal root ganglion (DRG) and sympathetic ganglion neurons, and mutations that
      enhance the activity of Nav1.7 have been shown to have profound effects on the
      excitability of both cell-types, suggesting that dysfunction of sympathetic
      and/or sensory fibers, which release vasoactive peptides at skin vasculature, may
      contribute to skin reddening in IEM and PEPD. RESULTS: In the present study, we
      demonstrate that smooth muscle cells of cutaneous arterioles and arteriole-venule
      shunts (AVS) in the skin express sodium channel Nav1.7. Moreover, Nav1.7 is
      expressed by endothelial cells lining the arterioles and AVS and by sensory and
      sympathetic fibers innervating these vascular elements. CONCLUSIONS: These
      observations suggest that the activity of mutant Nav1.7 channels in smooth muscle
      cells of skin vasculature and innervating sensory and sympathetic fibers
      contribute to the skin reddening and/or pain in IEM and PEPD.

PMID- 25957178
TI  - Diffusive and thermodiffusive transfer of magnetic nanoparticles in porous media.
AB  - Experimental results on mass transfer within a thin porous layer saturated with
      ferrofluid are outlined in this paper. From the analysis of particle
      concentration distribution across the layer it is shown that both the mass
      diffusion and the Soret coefficients of nanoparticles are remarkably less than
      those measured in free fluid. The particle transport coefficient changes due to
      an external uniform magnetic field qualitatively well agree with the predictions
      of existing theoretical research. The magnetic field that is oriented
      transversely to the porous layer causes an increase in the diffusion coefficient
      and a decrease in the Soret coefficient whilst the longitudinal field causes a
      reduction of the mass diffusion and an intensification of the particle
      thermodiffusion. 

PMID- 25957179
TI  - Macroscopic force experienced by extended objects in granular flows over a very
      broad Froude-number range : Macroscopic granular force on extended object.
AB  - This paper revisits a great number of data from previous studies about the
      macroscopic force experienced by either objects moving at constant speed and
      depth inside static granular materials or motionless objects subject to steady
      granular flows. It focuses on extended objects whose immersed height is equal or
      close to the thickness of the surrounding granular medium. A simple scaling
      argument allows demarcating quasi-static from speed-squared force contributions
      for all the data from different geometries over a very broad range of Froude
      number. However, a wide scatter of the data is observed in the quasi-static
      regime. In the first step, a mean-field model is proposed to describe the average
      force. Mass and momentum balances are applied to a control volume, namely the
      expected volume of grains disturbed by the object, which is assumed to extend
      across the whole width and the entire height of the granular system. This allows
      defining an equivalent length scale which is computed by fitting the force
      predicted by the model to the available force data. In the second step, a
      circular shape is assumed for the effective mobilized domain and the associated
      diameter can be directly extracted from the computed equivalent length scale.
      This effective diameter is found to vary linearly with both the object width and
      the thickness of the granular layer moving around the extended object or the
      immersed depth of the object. The scaling highlights the key role played by the
      geometry which may enhance the force in the quasi-static regime. 

PMID- 25957181
TI  - Analysis of correlation between white matter changes and functional responses in
      thalamic stroke: a DTI & EEG study.
AB  - Diffusion tensor imaging (DTI) allows in vivo structural brain mapping and
      detection of microstructural disruption of white matter (WM). One of the commonly
      used parameters for grading the anisotropic diffusivity in WM is fractional
      anisotropy (FA). FA value helps to quantify the directionality of the local tract
      bundle. Therefore, FA images are being used in voxelwise statistical analyses
      (VSA). The present study used Tract-Based Spatial Statistics (TBSS) of FA images
      across subjects, and computes the mean skeleton map to detect voxelwise knowledge
      of the tracts yielding to groupwise comparison. The skeleton image illustrates WM
      structure and shows any changes caused by brain damage. The microstructure of WM
      in thalamic stroke is investigated, and the VSA results of healthy control and
      thalamic stroke patients are reported. It has been shown that several skeleton
      regions were affected subject to the presence of thalamic stroke (FWE, p < 0.05).
      Furthermore the correlation of quantitative EEG (qEEG) scores and
      neurophysiological tests with the FA skeleton for the entire test group is also
      investigated. We compared measurements that are related to the same fibers across
      subjects, and discussed implications for VSA of WM in thalamic stroke cases, for
      the relationship between behavioral tests and FA skeletons, and for the
      correlation between the FA maps and qEEG scores.Results obtained through the
      regression analyses did not exceed the corrected statistical threshold values for
      multiple comparisons (uncorrected, p < 0.05). However, in the regression analysis
      of FA values and the theta band activity of EEG, cingulum bundle and corpus
      callosum were found to be related. These areas are parts of the Default Mode
      Network (DMN) where DMN is known to be involved in resting state EEG theta
      activity. The relation between the EEG alpha band power values and FA values of
      the skeleton was found to support the cortico-thalamocortical cycles for both
      subject groups. Further, the neurophysiological tests including Benton Face
      Recognition (BFR), Digit Span test (DST), Warrington Topographic Memory test
      (WTMT), California Verbal Learning test (CVLT) has been regressed with the FA
      skeleton maps for both subject groups. Our results corresponding to DST task were
      found to be similar with previously reported findings for working memory and
      episodic memory tasks. For the WTMT, FA values of the cingulum (right) that plays
      a role in memory process was found to be related with the behavioral responses.
      Splenium of corpus callosum was found to be correlated for both subject groups
      for the BFR.

PMID- 25957182
TI  - The Big Five Factor Marker Adjectives Are Not Especially Popular Words. Are They
      Superior Descriptors?
AB  - Vocabularies of natural languages evolve over time. Useful words become more
      popular and useless concepts disappear. In this study, the frequency of the use
      of 295 English, 100 German, and 114 French personality adjectives in book texts
      and Twitter messages as qualifiers of the words person, woman, homme, femme, and
      Person was studied. Word frequency data were compared to factor loadings from
      previous factor analytic studies on personality terms. The correlation between
      the popularity of an adjective and its highest primary loading in five- and six
      factor models was low (-0.12 to 0.17). The Big five (six) marker adjectives were
      not more popular than "blended" adjectives that had moderate loadings on several
      factors. This finding implies that laymen consider "blended" adjectives as
      equally useful descriptors compared to adjectives that represent core features of
      the five (six) factors. These results are compatible with three hypotheses: 1)
      laymen are not good at describing personality, 2) the five (six) factors are
      artifacts of research methods, 3) the interaction of the five (six) factors is
      not well understood.

PMID- 25957180
TI  - Colloquium: Mechanical formalisms for tissue dynamics.
AB  - The understanding of morphogenesis in living organisms has been renewed by
      tremendous progress in experimental techniques that provide access to cell scale,
      quantitative information both on the shapes of cells within tissues and on the
      genes being expressed. This information suggests that our understanding of the
      respective contributions of gene expression and mechanics, and of their crucial
      entanglement, will soon leap forward. Biomechanics increasingly benefits from
      models, which assist the design and interpretation of experiments, point out the
      main ingredients and assumptions, and ultimately lead to predictions. The newly
      accessible local information thus calls for a reflection on how to select
      suitable classes of mechanical models. We review both mechanical ingredients
      suggested by the current knowledge of tissue behaviour, and modelling methods
      that can help generate a rheological diagram or a constitutive equation. We
      distinguish cell scale ("intra-cell") and tissue scale ("inter-cell")
      contributions. We recall the mathematical framework developed for continuum
      materials and explain how to transform a constitutive equation into a set of
      partial differential equations amenable to numerical resolution. We show that
      when plastic behaviour is relevant, the dissipation function formalism appears
      appropriate to generate constitutive equations; its variational nature
      facilitates numerical implementation, and we discuss adaptations needed in the
      case of large deformations. The present article gathers theoretical methods that
      can readily enhance the significance of the data to be extracted from recent or
      future high throughput biomechanical experiments. 

PMID- 25957183
TI  - eMoms: Electronically-mediated weight interventions for pregnant and postpartum
      women. Study design and baseline characteristics.
AB  - BACKGROUND: The influence of childbearing in the development of obesity is
      situated within two different but related contexts: pregnancy-related weight gain
      and weight gain prevention and control in young adult women. Pregnancy related
      weight gain contributes to long-term weight retention in childbearing women.
      OBJECTIVE: To present the study design, data collection procedures, recruitment
      challenges, and the baseline characteristics for the eMoms of Rochester study, a
      randomized clinical trial testing the effect of electronically-mediated
      behavioral interventions to prevent excessive gestational weight gain (GWG) and
      postpartum weight retention among women aged 18-35 years of diverse income and
      racial/ethnic backgrounds in an urban setting. DESIGN: Randomized double blind
      clinical trial. A total of 1722 women at or below 20 weeks of gestation were
      recruited primarily from obstetric practices and randomized to 3 treatment
      groups: control arm; intervention arm with access to intervention during
      pregnancy and control at postpartum (e-intervention 1); and intervention arm with
      access to intervention during pregnancy and postpartum (e-intervention 2).
      Enrollment and consent were completed via study staff or online. Data were
      collected via online surveys, medical charts, and measurement of postpartum
      weights. The primary endpoints are gaining more weight than recommended by the
      Institution of Medicine guidelines and weight retained at 12 months postpartum.
      CONCLUSION: This study will provide evidence on the efficacy of behavioral
      interventions in the prevention of excessive GWG and postpartum weight retention
      with potential dissemination to obstetric practices and/or health insurances.
      ClinicalTrials.gov #NCT01331564.

PMID- 25957184
TI  - Definitive radiation therapy in locally advanced non-small cell lung cancer:
      Executive summary of an American Society for Radiation Oncology (ASTRO) evidence
      based clinical practice guideline.
AB  - PURPOSE: To provide guidance to physicians and patients with regard to the use of
      definitive external beam radiation therapy (RT) in locally advanced non-small
      cell lung cancer (LA NSCLC) based on available medical evidence complemented by
      consensus-based expert opinion. METHODS AND MATERIALS: A panel authorized by the
      American Society for Radiation Oncology (ASTRO) Board of Directors and Guidelines
      Subcommittee conducted 3 systematic reviews on the following topics: (1) ideal
      radical RT dose fractionation for RT alone; (2) ideal radical RT dose
      fractionation for chemoradiation; and (3) ideal timing of radical radiation
      therapy with systemic chemotherapy. Practice guideline recommendations were
      approved using an a priori-defined consensus-building methodology supported by
      ASTRO and approved tools for the grading of evidence quality and the strength of
      guideline recommendations. RESULTS: For patients managed by RT alone, a minimum
      dose of 60 Gy of RT is recommended. Dose escalation beyond 60 Gy in the context
      of combined modality concurrent chemoradiation has not been found to be
      associated with any clinical benefits. In the context of combined modality
      therapy, chemotherapy and radiation should ideally be given concurrently to
      maximize survival, local control, and disease response rate. CONCLUSIONS: A
      consensus and evidence-based clinical practice guideline for the definitive
      radiotherapeutic management of LA NSCLC has been created that addresses 3
      important questions.

PMID- 25957185
TI  - Adjuvant radiation therapy in locally advanced non-small cell lung cancer:
      Executive summary of an American Society for Radiation Oncology (ASTRO) evidence
      based clinical practice guideline.
AB  - PURPOSE: To provide guidance to physicians and patients with regard to the use of
      adjuvant external beam radiation therapy (RT) in locally advanced non-small cell
      lung cancer (LA NSCLC) based on available medical evidence complemented by
      consensus-based expert opinion. METHODS AND MATERIALS: A panel authorized by the
      American Society for Radiation Oncology (ASTRO) Board of Directors and Guidelines
      Subcommittee conducted 2 systematic reviews on the following topics: (1)
      indications for postoperative adjuvant RT and (2) indications for preoperative
      neoadjuvant RT. Practice guideline recommendations were approved using an a
      priori-defined consensus-building methodology supported by ASTRO and approved
      tools for the grading of evidence quality and the strength of guideline
      recommendations. RESULTS: For patients who have undergone surgical resection,
      high-level evidence suggests that use of postoperative RT does not influence
      survival, but optimizes local control for patients with N2 involvement, and its
      use in the setting of positive margins or gross primary/nodal residual disease is
      recommended. No high-level evidence exists for the routine use of preoperative
      induction chemoradiation therapy; however, modern surgical series and a post-hoc
      Intergroup 0139 clinical trial analysis suggest that a survival benefit may exist
      if patients are properly selected and surgical techniques/postoperative care is
      optimized. CONCLUSIONS: A consensus and evidence-based clinical practice
      guideline for the adjuvant radiotherapeutic management of LA NSCLC has been
      created addressing 2 important questions.

PMID- 25957186
TI  - Modeled risk of ischemic heart disease following left breast irradiation with
      deep inspiration breath hold.
AB  - PURPOSE: Deep inspiration breath hold (DIBH) dramatically reduces radiation dose
      to the heart during radiation therapy (RT) for left-sided breast cancer, but the
      subsequent risk of radiation-related ischemic heart disease (IHD) is unknown. Our
      primary objective was to quantify the risk of IHD following RT with DIBH using
      modeled risk estimates (MRE). METHODS AND MATERIALS: Patients with stage 0-III
      left-sided breast cancer who received RT with DIBH were retrospectively studied.
      Computed tomography simulations were performed with DIBH and during free
      breathing (FB) for comparison of dosimetry. Patients were classified as high
      risk, at risk, or at optimal risk for IHD and baseline risk estimates for IHD
      were obtained from historic controls. The excess relative risk of IHD because of
      left breast RT was calculated using patient-specific dosimetry and an existing
      dose-effect model. MRE were determined from the sum of baseline risk estimates
      and excess risk. RESULTS: Between 2002 and 2011, 111 patients were treated using
      DIBH and 104 were available for analysis. MRE for 10-year risk of IHD with DIBH
      and FB were 3.25% (interquartile range [IQR], 1.20-3.44) and 3.64% (IQR, 1.43
      3.81) (P < .0001), respectively. MRE for lifetime risk of IHD with DIBH and FB
      were 9.71% (IQR, 1.98-16.62) and 10.28% (IQR, 2.05-16.97) (P < .0001),
      respectively. MRE were significantly reduced by use of DIBH in all risk groups.
      The largest absolute risk reduction resulting from the DIBH technique was
      observed in patients at high risk for IHD. The median relative risk reduction in
      MRE resulting from DIBH was 11.4% (range, 0-32.0) and 6.4% (range, 0-23.4) at 10
      years and throughout the patients' lifetime, respectively. After a median follow
      up of 7.0 years (range, 1.3-11.2), the estimated 10-year freedom from IHD was
      99.0% (95% confidence interval 93.4-99.8). CONCLUSIONS: RT with DIBH may provide
      breast cancer survivors a clinically significant reduction in the risk of IHD.

PMID- 25957187
TI  - Natural history of testicular size in boys with varicoceles.
AB  - INTRODUCTION: Testicular size is commonly used as a proxy for future fertility in
      adolescent boys diagnosed with varicoceles. Surgery is often performed based on a
      15-20% reduction in volume of the ipsilateral testicle when compared to the
      unaffected side. Recent European Association of Urology guidelines, however, have
      highlighted the risk of overtreatment. Data on the natural progression of
      testicular size discrepancy are limited in this population. To evaluate the role
      of a non-surgical approach, the present study reports on testicular size
      progression in 35 boys with left-sided varicoceles managed with observation
      alone. METHODS: In the present study, 103 consecutive boys who were seen for
      varicocele were retrospectively evaluated; the 35 who were seen for at least
      three sequential visits by the same pediatric urologist for a unilateral left
      varicocele were selected. In the present practice, surgical management of
      varicoceles in teens is offered, but not recommended unless surgery is being
      performed for another reason (3/103). The Prader orchidometric testicular volumes
      that were documented for all visits were recorded and the volume of the left
      testicle as a percentage of the right was calculated. This analysis was performed
      for the entire population, and subgroup analysis was conducted for boys with a
      Grade 3 varicocele, with >10% asymmetry at diagnosis, and by dividing the
      population into prepubertal and pubertal age groups. Boys with bilateral
      varicoceles, concurrent testicular masses, or volumes recorded by a nurse
      practitioner were excluded from the study. RESULTS: The mean left testicular
      volume in the population was found to measure 96%, 95% and 96% of the right at
      the first, second and third visit (median interval was 2.0 years), respectively.
      Among the 26 boys seen for a fourth visit (median 3.3 years) and the 15 seen for
      a fifth visit (median 4.3 years), the mean left testicular volumes were 98% and
      97% of the right at diagnosis and 97% at both the fourth and fifth visits
      (Figure). Likewise, no differences were seen after dividing the population into
      prepubertal (9-11 years, n = 9) and pubertal (12-14 years, n = 26) groups. Among
      the 13 (37%) boys with a Grade 3 varicocele at presentation, the left testicular
      volume was 95% (SD 11.4) of the right and remained unchanged by the third visit
      (96%, P = 0.69). In addition, among the 11 boys (31%) with greater than 10% size
      difference at the first visit, the left testicle measured 82% of the right (SD
      5.3) at diagnosis and increased to 92% (SD 6.3) by the third visit (P < 0.001).
      DISCUSSION: In the 35 boys observed over a median of 2.0 years or three
      consecutive visits, there was no worsening of testicular asymmetry. This finding
      is consistent with some previous observational data on pediatric varicoceles, but
      carries the advantages of a narrower age range and longitudinal follow-up in all
      patients. At the same time, these results differ from other studies that show no
      improvement or worsening of asymmetry during follow-up. This difference is
      attributed to the inherent characteristics of the present study population and
      the choice of orchidometer for measurement. The present data have the advantage
      of excluding selection bias. Recognizing that this study is a retrospective,
      single-operator study with a small sample size, prospective, randomized trials
      are recommended to weigh surgery vs observation in adolescent varicocele
      patients. CONCLUSIONS: No progression in atrophy/hypotrophy of the left testis
      was found in a series of 35 consecutive patients who were followed non-surgically
      for left-sided varicocele. Our data thus support observation as management for
      childhood varicocele in younger teens.

PMID- 25957188
TI  - Commentary to: No effect of basic bladder advice in enuresis--A randomized
      controlled trial.

PMID- 25957189
TI  - Insights into the mechanisms underlying the antitumor activity of an
      oxidovanadium(IV) compound with the antioxidant naringenin. Albumin binding
      studies.
AB  - Naringenin, a natural antioxidant present in grapefruit, oranges and the skin of
      tomatoes showed low antioxidant properties among other flavonoids due to its
      structural characteristics. Since many flavonoids were shown to have cell-killing
      and antioxidant activities, naringenin was investigated herein. In parallel with
      its antioxidant activities the flavonoid showed very low cytotoxicity at
      concentrations up to 100 MUM against lung (A549) and breast (SKBr3 and MDAMB231)
      cancer cell lines. Furthermore, a newly-synthesized and characterized complex of
      naringenin and oxidovanadium(IV) ([V(IV)O(nar)2] . 2H2O, VOnar, with weak
      ferromagnetic coupling) was also studied. As a result, VOnar acted as a better
      compound on cell-killing and antioxidant activities (in vitro) than naringenin.
      The anti-proliferative effect of VOnar was accompanied by reactive oxygen species
      (ROS) generation, cell membrane and DNA damages, cell cycle arrest, caspase 3/7
      activation and mitochondrial potential reduction. The higher parameters observed
      for the MDAMB231 cell line have been related to its low glutathione (GSH)
      content. The assays of the interaction of bovine serum albumin (BSA) with the
      complex showed the affinity of protein toward it and that there is only one
      binding site on the BSA molecule. However, metal complexation decreased the
      binding affinity to BSA of naringenin probably due to a steric hindrance of the
      complex.

PMID- 25957190
TI  - Effects of nutritional programing on growth and metabolism caused by albumen
      removal in an avian model.
AB  - In mammalian models of prenatal undernutrition the maternal diet is manipulated,
      exerting both nutritional and hormonal effects on the offspring. In contrast, in
      the chicken, strictly nutritional effects can be applied. Prenatal protein
      undernutrition in chickens was induced by partial replacement of albumen with
      saline during early embryonic development (albumen-deprived group) and results
      were compared with a sham-manipulated and a non-manipulated group. Body weight of
      the albumen-deprived hens was reduced throughout the entire experimental period
      (0-55 weeks). The reproductive capacity was diminished in the albumen-deprived
      hens as reflected in the reduced number of eggs and lower egg weight. The plasma
      triiodothyronine levels were increased in the albumen-deprived group compared
      with the non-manipulated hens, but not the sham-manipulated hens. An oral glucose
      tolerance test (OGTT) at 10 weeks of age revealed a decreased glucose tolerance
      in the albumen-deprived hens. During adulthood, an age-related loss of glucose
      tolerance was observed in the hens, leading to disappearance of treatment
      differences in the OGTT. The offspring of the albumen-deprived hens (PA chicks)
      had reduced body weight until at least 3 weeks of age. In addition, the PA chicks
      had a decreased relative residual yolk weight at hatching. An insulin tolerance
      test revealed increased sensitivity to insulin for the PA chicks compared with
      the offspring of the non-manipulated (PN) and sham-manipulated hens (PS). In
      conclusion, prenatal protein undernutrition by albumen removal caused long-term
      effects on body weight, reproductive performance, and physiology.

PMID- 25957191
TI  - The involvement of gonadotropin inhibitory hormone and kisspeptin in the
      metabolic regulation of reproduction.
AB  - Recently, kisspeptin (KP) and gonadotropin inhibitory hormone (GnIH), two
      counteracting neuropeptides, have been acknowledged as significant regulators of
      reproductive function. KP stimulates reproduction while GnIH inhibits it. These
      two neuropeptides seem to be pivotal for the modulation of reproductive activity
      in response to internal and external cues. It is well-documented that the current
      metabolic status of the body is closely linked to its reproductive output.
      However, how reproductive function is regulated by the body's energy status is
      less clear. Recent studies have suggested an active participation of hypothalamic
      KP and GnIH in the modulation of reproductive function according to available
      metabolic cues. Expression of KISS1, the KP encoding gene, is decreased while
      expression of RFRP (NPVF), the gene encoding GnIH, is increased in metabolic
      deficiency conditions. The lower levels of KP, as suggested by a decrease in
      KISS1 gene mRNA expression, during metabolic deficiency can be corrected by
      administration of exogenous KP, which leads to an increase in reproductive
      hormone levels. Likewise, administration of RF9, a GnIH receptor antagonist, can
      reverse the inhibitory effect of fasting on testosterone in monkeys. Together, it
      is likely that the integrated function of both these hypothalamic neuropeptides
      works as a reproductive output regulator in response to a change in metabolic
      status. In this review, we have summarized literature from nonprimate and primate
      studies that demonstrate the involvement of KP and GnIH in the metabolic
      regulation of reproduction.

PMID- 25957192
TI  - Regionalizing land use impacts on farmland birds.
AB  - The environmental impacts of land use vary regionally. Differences in
      geomorphology, climate, landscape structure, and biotope inventories are regarded
      as the main causes of this variation. We present a methodological approach for
      identifying regional responses in land use type to large-scale changes and the
      implications for the provision of habitat for farmland birds. The methodological
      innovations of this approach are (i) the coupling of impact assessments with
      economic models, (ii) the linking of cropping techniques at the plot scale with
      the regional distribution of land use, and (iii) the integration of statistical
      or monitoring data on recent states. This approach allows for the regional
      differentiation of farmers' responses to changing external conditions and for
      matching the ecological impacts of land use changes with regional environmental
      sensitivities. An exemplary scenario analysis was applied for a case study of an
      area in Germany, assessing the impacts of increased irrigation and the promotion
      of energy cropping on farmland birds, evaluated as a core indicator for farmland
      biodiversity. The potential effects on farmland birds were analyzed based on the
      intrinsic habitat values of the crops and cropping techniques. The results
      revealed that the strongest decrease in habitat availability for farmland birds
      occurred in regions with medium-to-low agricultural yields. As a result of the
      limited cropping alternatives, the increase in maize production was highest in
      marginal regions for both examined scenarios. Maize production replaced many
      crops with good-to-medium habitat suitability for birds. The declines in habitat
      quality were strongest in regions that are not in focus for conservation efforts
      for farmland birds. 

PMID- 25957193
TI  - Sampling of riverine litter with citizen scientists--findings and
      recommendations.
AB  - The quantity and composition of litter at riversides and in the surface waters,
      as well as the occurrence of illegal dumping sites, were studied along four
      rivers in Chile. Data generated by volunteers were compared to the results from a
      professional survey, using an identical protocol. Litter was found in
      considerable quantities at the riversides and in the surface waters at all the
      sites investigated. A generalized linear mixed model analysis showed that the
      recorded litter densities did not differ between volunteers and professionals,
      even after controlling for river, site, or distance between sampling locations,
      demonstrating that the volunteers successfully applied the sampling protocol.
      Differences occurred with respect to litter composition, which is most likely due
      to difficulties in the classification of litter items and particles and to the
      underestimation of litter present in surface water samples. Even though this
      study was only conducted at a small number of rivers and sites, a comparatively
      consistent pattern of direct and intentional litter deposition at riversides was
      recorded, highlighting that river basins require more protection. The results
      also show that the citizen science approach can be a suitable means for more
      extensive litter surveys at riversides and in other natural environments. 

PMID- 25957194
TI  - Assessment of trace metal pollution in sediments and intertidal fauna at the
      coast of Cameroon.
AB  - Coastal systems act as a boundary between land and sea. Therefore, assessing
      pollutant concentrations at the coast will provide information on the impact that
      land-based anthropogenic activities have on marine ecosystems. Sediment and fauna
      samples from 13 stations along the whole coast of Cameroon were analyzed to
      assess the level of trace metal pollution in sediments and intertidal fauna.
      Sediments showed enrichment of As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, V, and Zn.
      However, pollution of greater concern was observed for Cd, Cr, Cu, Ni, and Zn at
      the northern stations. Some sites recorded trace metal levels higher than
      recommended in sediment quality guidelines. Species diversity was low, and high
      bioaccumulation of trace metals was observed in biological samples. Some edible
      gastropod species accumulated trace metals above the safety limits of the World
      Health Organization, European Medicine Agency, and the US Environment Protection
      Agency. Although industrial pollution is significant along Cameroon's coast,
      natural pollution from the volcano Mount Cameroon is also of concern. 

PMID- 25957195
TI  - Bioaccumulation of metals in three freshwater mussel species exposed in situ
      during and after dredging at a coal ash spill site (Tennessee Valley Authority
      Kingston Fossil Plant).
AB  - On December 22, 2008, a dike containing coal fly ash at the Tennessee Valley
      Authority Kingston Fossil Plant (TN, USA) failed, and within months, dredging
      operations began to remove ash-contaminated sediments. The purpose of this study
      was to investigate differences in the bioaccumulation of metals in three mussel
      species during and after dredging operations. Mussels were caged for
      approximately 1 year during dredging and after, and then mussel condition index
      values and As, Cd, Cr, Pb, Ni, Se, Hg, U, Fe, Mg, Al, Sb, Ba, Be, Co, Cu, Mn, Mo,
      Ag, Sr, Tl, V, and Zn concentrations in soft tissue were determined via
      inductively coupled plasma-mass spectrometery. Overall, the differences observed
      in metal bioaccumulation and mussel health suggest that mussels in the immediate
      downstream area of the dredging site may have been impacted, as evidenced by a
      significant decrease in mussel condition index values, but that this impact did
      not result in increased tissue concentrations of metals.

PMID- 25957196
TI  - The roles of emotional competence and social problem-solving in the relationship
      between physical abuse and adolescent suicidal ideation in China.
AB  - The study investigated the relationship among physical abuse, positive
      psychological factors including emotional competence and social problem-solving,
      and suicidal ideation among adolescents in China. The possible moderating effects
      of emotional competence and social problem-solving in the association between
      physical abuse and adolescent suicidal ideation were also studied. A cross
      sectional survey employing convenience sampling was conducted and self
      administered questionnaires were collected from 527 adolescents with mean age of
      14 years from the schools in Shanghai. Results showed that physical abuse was
      significantly and positively related to suicidal ideation in both male and female
      adolescents. Emotional competence was not found to be significantly associated
      with adolescent suicidal ideation, but rational problem-solving, a sub-scale of
      social problem-solving, was shown to be significantly and negatively associated
      with suicidal ideation for males, but not for females. However, emotional
      competence and rational problem-solving were shown to be a significant and a
      marginally significant moderator in the relationship between physical abuse and
      suicidal ideation in females respectively, but not in males. High rational
      problem-solving buffered the negative impact of physical abuse on suicidal
      ideation for females. Interestingly, females with higher empathy and who reported
      being physically abused by their parents have higher suicidal ideation. Findings
      are discussed and implications are stated. It is suggested to change the
      attitudes of parents on the concept of physical abuse, guide them on appropriate
      attitudes, knowledge and skills in parenting, and enhance adolescents' skills in
      rational problem-solving. 

PMID- 25957197
TI  - Association of autistic traits in adulthood with childhood abuse, interpersonal
      victimization, and posttraumatic stress.
AB  - Persons with autistic traits may be at elevated risk for interpersonal
      victimization across the life course. Children with high levels of autistic
      traits may be targeted for abuse, and deficits in social awareness may increase
      risk of interpersonal victimization. Additionally, persons with autistic traits
      may be at elevated risk of posttraumatic stress disorder (PTSD) symptoms
      subsequent to trauma. We examined retrospectively reported prevalence of
      childhood abuse, trauma victimization and PTSD symptoms by autistic traits among
      adult women in a population-based longitudinal cohort, the Nurses' Health Study
      II (N=1,077). Autistic traits were measured by the 65-item Social Responsiveness
      Scale. We estimated odds ratios (OR) for childhood sexual and physical/emotional
      abuse and PTSD symptoms by quintiles of autistic traits. We examined possible
      mediation of PTSD risk by abuse and trauma type. Women in the highest versus
      lowest quintile of autistic traits were more likely to have been sexually abused
      (40.1% versus 26.7%), physically/emotionally abused (23.9% versus 14.3%), mugged
      (17.1% versus 10.1%), pressured into sexual contact (25.4% versus 15.6%) and have
      high PTSD symptoms (10.7% versus 4.5%). Odds of PTSD were elevated in women in
      the top three quintiles of autistic traits compared with the reference group (OR
      range=1.4 to 1.9). Childhood abuse exposure partly accounted for elevated risk of
      PTSD in women with autistic traits. We identify for the first time an association
      between autistic traits, childhood abuse, trauma victimization, and PTSD. Levels
      of autistic traits that are highly prevalent in the general population are
      associated with abuse, trauma and PTSD. 

PMID- 25957198
TI  - Clinical pharmacokinetic and pharmacodynamic profile of lacosamide.
AB  - Lacosamide-a third-generation antiepileptic drug available in multiple
      formulations-was first approved in 2008 as adjunctive therapy for partial-onset
      seizures (POS) in adults. In 2014, lacosamide was approved as monotherapy for POS
      by the US Food and Drug Administration (FDA). A loading dose administration was
      approved in 2013 by the European Medicines Agency and in 2014 by the FDA. Unlike
      traditional sodium channel blockers affecting fast inactivation, lacosamide
      selectively enhances sodium channel slow inactivation. This mechanism of action
      results in stabilization of hyperexcitable neuronal membranes, inhibition of
      neuronal firing and reduction in long-term channel availability without affecting
      physiological function. Lacosamide is rapidly absorbed, with maximum plasma
      concentrations reached 0.5-4 h after intake. Oral bioavailability is high (100 %)
      for a dose up to 800 mg. Bioavailability is irrespective of food intake.
      Variability in pharmacokinetic parameters is low (coefficients of variation
      almost all <20 %). The pharmacokinetic profile of lacosamide is consistent in
      healthy subjects and across different patient populations studied. Lacosamide
      elimination from plasma occurs with a terminal half-life of approximately 13 h in
      young subjects and 14-16 h in elderly subjects; this difference does not impact
      the dose regimen. Lacosamide produces a pharmacodynamic effect that is closely
      correlated with its plasma concentration. The pharmacokinetic and pharmacodynamic
      relationship for reduction of seizure frequency can be described by a maximum
      effect (E max) model. Lacosamide does not induce or inhibit cytochrome P450
      enzymes or known drug transporter systems, has low protein binding of less than
      15 % and, because it has multiple elimination pathways, it has no clinically
      relevant interactions with commonly prescribed medications. 

PMID- 25957199
TI  - Inhibitory effect of l-mimosine on bleomycin-induced pulmonary fibrosis in rats:
      Role of eIF3a and p27.
AB  - It has also been shown that the decreased expression of eukaryotic translation
      initiation factor 3a (eIF3a) by L-mimosine caused cell cycle arrest. Our previous
      study has found that eIF3a is involved in bleomycin-induced pulmonary fibrosis.
      Whether the eIF3a/p27 signal pathway is involved in the inhibitory effect of L
      mimosine on bleomycin-induced pulmonary fibrosis remains unknown. Pulmonary
      fibrosis was induced by intratracheal instillation of bleomycin (5 mg/kg) in
      rats. Primary pulmonary fibroblasts were cultured to investigate the
      proliferation by BrdU incorporation method and flow cytometry. The expression of
      eIF3a, p27, alpha-SMA, collagen I and collagen III was analyzed by qPCR and
      Western blot. In vivo, L-mimosine treatment significantly ameliorated the
      bleomycin-mediated histological fibrosis alterations and blocked collagen
      deposition concomitantly with reversing bleomycin-induced expression up
      regulation of eIF3a, alpha-SMA, collagen I and collagen III (both mRNA and
      protein) and expression down- regulation of p27. In vitro, L-mimosine remarkably
      attenuated proliferation of pulmonary fibroblasts and expression of alpha-SMA,
      collagen I and collagen III induced by TGF-beta1, and this inhibitory effect of L
      mimosine was accompanied by inhibiting eIF3a expression and increasing p27
      expression. Knockdown of eIF3a gene expression reversed TGF-beta1-induced
      proliferation of fibroblasts, down-regulation of p27 expression and up-regulation
      of alpha-SMA, collagen I, and collagen III expression. These results suggest that
      L-mimosine inhibited the progression of bleomycin-induced pulmonary fibrosis in
      rats via the eIF3a/p27 pathway.

PMID- 25957200
TI  - Molecular mechanisms of synergy of corneal muscarinic and nicotinic acetylcholine
      receptors in upregulation of E-cadherin expression.
AB  - Corneal epithelial erosion is one of the most common problems in clinical
      ophthalmology. Despite significant progress in understanding how the cornea
      heals, clinically available pharmacological therapies that can promote repair and
      prevent visual complications remain limited. We have recently demonstrated that
      the acetylcholine (ACh) axis of corneal epithelium plays an important role in
      regulation and coordination of distinct activities of corneal epithelial cells
      (CEC) mediating re-epithelialization, but mechanisms remained unclear. We
      hypothesized that the grounds for synergistic effects of corneal ACh receptors
      lie within the signaling pathways linking different receptors to specific
      elements of the CEC pro-epithelialization activities. In this study, we sought to
      elucidate the molecular mechanisms of cooperation of corneal muscarinic and
      nicotinic ACh receptors (mAChRs and nAChRs) in upregulation of E-cadherin
      expression. The roles of individual corneal mAChRs and nAChRs subtypes were
      investigated by in-cell western assay of the ACh-treated CEC, in which different
      ACh receptor genes were silenced by receptor-specific shRNAs. Functional
      inactivation of M3, but not M4, mAChR subtype, or alpha3 or alpha7, but not
      alpha9, nAChR subunit significantly inhibited E-cadherin expression. To gain a
      mechanistic insight, we blocked the key steps of the downstream signaling
      pathways. Results demonstrated that cholinergic agonists can upregulate E
      cadherin expression by activating M3 mAChR, and alpha3beta2 and alpha7 nAChRs via
      the common signaling cascade Ca(2+)-CaMKII-PKC-Ras-Raf-MEK-ERK. Activation of
      alpha7 nAChR can launch the Ras-Raf-MEK-ERK cascade both indirectly, through the
      Ca(2+)-CaMKII-PKC step, and directly, perhaps, due to its direct interaction with
      Ras. Although the biological significance of such redundancy remained to be
      elucidated, results of the present study point to a new direction to
      pharmacologically accelerate corneal re-epithelialization, and should have
      salient clinical implication. 

PMID- 25957201
TI  - [Nonconvulsive status epilepticus; progress in clinical practice and research].
AB  - Mainly after 2000, we have reported novel manifestations of nonconvulsive status
      epilepticus (NCSE), such as reversible protracted coma, posthyperventilation
      apnea, and higher brain dysfunctions, including Kluver-Bucy syndrome. In this
      review, we discuss the progress in clinical practice and research of NCSE with
      best available evidence, especially the spectrum of electroencephalographic
      abnormalities in NCSE, clinical manifestations of malignant NCSE, relationship
      between sudden unexpected death in epilepsy (SUDEP) and NCSE, and a strategy for
      real-time neuromonitoring. In addition, we propose some new concepts, NCSE, such
      as the antiepileptic drug-responsive neurological deficit (ADND), critical NCSE,
      fosphenytoin challenge test, epilepsy-related organ dysfunction (Epi-ROD), and a
      Neurocritical Score (Integrated Scale) for the comprehensive and serial
      evaluation of neurocritical conditions. We emphasize the need for the
      neuromonitoring of NCSE of broader neurological and neurocritical manifestations
      not only in the intensive care unit but also in the emergency room, outpatient
      clinic, inpatient ward, and social settings. 

PMID- 25957202
TI  - [Association between Elderly Onset Epilepsy and Dementia].
AB  - Japan is experiencing an increase in the number of patients with dementia, and
      the incidence of epilepsy is high among the elderly. A survey of patients with
      epilepsy who were admitted to our hospital's neurology department showed that new
      onset epilepsy occurred more frequently in elderly patients. In addition, a
      greater proportion of elderly patients had dementia as an underlying disease.
      Although the prevalence of epilepsy in dementia varies, higher brain dysfunctions
      are known to be related to epilepsy. Because a symptom of epilepsy may be
      mistaken for dementia, it is important to understand the association between
      epilepsy and dementia, including their tendencies and characteristics. 

PMID- 25957203
TI  - [Nonconvulsive status epilepticus in neurological emergencies].
AB  - According to the 2010 neuroresuscitation guideline, status epilepticus (SE) is a
      critical condition that causes respiratory and circulation dysfunction, including
      "acute consciousness disturbance" and "elevated intracranial pressure." There are
      two types of SE: general convulsive SE (GCSE) and nonconvulsive SE (NCSE). GCSE
      is easily diagnosed because the patients show continuous convulsions. In
      contrast, NCSE can only be diagnosed by electroencephalography (EEG), which can
      delay diagnosis. Moreover, GCSE and NCSE occasionally manifest in the same
      patient and alternate. Here, we describe the case of a 64-year-old male patient
      who experienced losses of consciousness mimicking stroke. We could not diagnose
      these episodes as NCSE until the patient had a general continuous convulsion. In
      this case, the delayed diagnosis of NCSE resulted in uncontrollable GCSE that
      required intensive management, including mechanical ventilation under sedation.
      It is important to recognize that NCSE can cause consciousness disturbance and to
      initiate treatment as soon as possible to improve patient prognosis. This could
      be achieved by performing an EEG earlier, such as at the scene of emergencies. 

PMID- 25957204
TI  - [Electroencephalographic features of nonconvulsive status epilepticus].
AB  - Continuous EEG monitoring (cEEG) has been recently applied in a neurocritical
      care setting in the US. The purpose of cEEG is primarily to detect nonconvulsive
      status epilepticus (NCSE) and secondarily, to evaluate the treatment of NCSE. It
      is difficult to diagnose NCSE in cEEG because of its variability. In the American
      Clinical Neurophysiology Society's Standardized Critical Care EEG Terminology
      2012, EEG localization is placed under major term 1 and is classified as
      Lateralized (L), Generalized (G), Bilateral Independent (BI), and Multifocal
      (Mf). Morphology is placed under major term 2 and is classified as periodic,
      rhythmic, and spike-and-wave. Although there are no unequivocal criteria for the
      diagnosis of NCSE, the appearance of spatial and temporal changes in the EEG is
      essential for diagnosis. 

PMID- 25957205
TI  - [Ring (20) chromosome epileptic syndrome].
AB  - Ring (20) chromosome epilepsy syndrome is characterized by highly refractory
      epilepsy that is often associated with non-pathognomonic, electroencephalographic
      (EEG) changes. Seizures typically begin during the stage of childhood around the
      age of 6 years. Nonconvulsive status epilepticus (NCSE) is the most common
      seizure types and is distinguished by a long-lasting, confusional state that is
      often associated with EEG patterns in the form of prolonged, high-voltage slow
      waves with occasional spike/sharp components. Patients with this syndrome suffer
      from intractable seizures with cognitive decline and frequent epileptic episodes.
      Accompanying features of this rare disorder, such as superficial minor dysmorphic
      abnormalities if any, mental retardation and behavioral changes are quite
      variable. Because of the variability in clinical presentation, in particular the
      lack of clear dysmorphic features, the clinical diagnosis of this disorder can be
      delayed before being diagnosed genetically. Most patients with this syndrome have
      chromosomal changes in the form of a mosaic. High levels of mosaicism correlate
      well with a lower age of onset and severe cognitive impairment. Here, we
      emphasize the importance of early G-banding chromosomal analysis when patients
      present with unexplainable severe seizures and repetitive NCSE, even in the
      absence of any dysmorphic features suggestive of a chromosomal disorder. 

PMID- 25957206
TI  - [Memory engram of brain circuit].
AB  - How are memories stored in the brain and retrieved on demand? This is a
      frequently asked question. Indeed, we acquire new memories daily and remember old
      ones. However, how we can memorize one-time experiences is yet to be
      investigated. Here, we review possible mechanisms by which memories are
      maintained in neural networks. 

PMID- 25957207
TI  - [Clinical significance of sudomotor evaluation for neurological diagnosis].
AB  - Human sweating is functionally classified into thermoregulatory, emotional, and
      gustatory sweating. Several central and peripheral nervous structures are
      involved in the sudomotor systems. Therefore, an anatomical understanding of the
      sudomotor systems and clinical evaluation of its function are useful for regional
      neurological diagnose. In addition, some neurological diseases may present
      characteristic abnormalities of sweating. This systematic review summarizes the
      anatomy, physiology, and symptomatology of sweating as well as the clinical
      characteristics of abnormal sweating in neurological disorders. 

PMID- 25957208
TI  - [New findings and concepts on production and absorption of cerebrospinal fluid:
      reconsiderations and revisions of an unquestioningly accepted dogma of 100
      years].
AB  - It has been recently pointed out that there are fallacies in the bulk flow
      theory, a dogmatic idea of cerebrospinal fluid (CSF) physiology, which assumes
      that CSF is produced by the choroid plexus and circulates unidirectionally from
      the ventricles to the subarachnoid space to be absorbed by the arachnoid villi in
      the parietal region. Therefore, CSF physiology now needs to be reconsidered.
      Since there is free exchange of water between the CSF and the brain interstitial
      fluid (ISF), when considering the dynamics of water in the brain, we should
      regard these two fluid compartments collectively as brain extracellular fluid. In
      this review, I discuss the contentious issues in the traditional theory of CSF
      physiology, and then introduce new understandings of the production and
      absorption of the brain extracellular fluid, such as the capillary theory
      asserting that brain ISF is produced and absorbed mainly at the cerebral
      capillaries, the brain lymphatic drainage pathway, and the non-existence of
      unidirectional CSF circulation. 

PMID- 25957209
TI  - [Neuro-otological Studies of Patients Suffering from Dizziness with Cerebrospinal
      Fluid Hypovolemia after Traffic Accident-associated Whiplash Injuries].
AB  - Vertigo and dizziness are common clinical manifestations after traffic accident
      associated whiplash injury. Recently, Shinonaga et al. (2001) suggested that more
      than 80% of patients with whiplash injury complaining of these symptoms showed
      cerebrospinal (CSF) hypovolemia on radioisotope (RI) cisternography (111In-DTPA).
      However, neuro-otological studies to investigate the pathophysiological
      mechanisms underlying these symptoms have been insufficient. In the present
      study, patients complaining of these symptoms with CSF hypovolemia after traffic
      accidents were investigated with posturography and electronystagmography (ENG).
      Fourteen patients (4 men, 10 women; 24-52 yr) were examined with posturography
      and showed parameters (tracking distance & area) significantly (p<0.01) larger
      than those of healthy subjects. Among them, five cases (1 man, 4 women; 31-52 yr)
      were further investigated with ENG. The slow phase peak velocities of optokinetic
      nystagmus (OKN) and optokinetic-after nystagmus (OKAN) were significantly
      (p<0.01) reduced (62.64+/-6.9 SD deg/sec, 60.76+/-10.74 SD deg/sec, respectively)
      and frequencies of OKN were reduced (139.7+/-10.75 SD), while the ocular smooth
      pursuit was relatively preserved. Magnetic resonance images (sagittal view) of
      these five patients demonstrated the downward displacement of the cerebellar
      tonsils and flattening of the pons, which are characteristic features of CSF
      hypovolemia, called "brain sagging." Our results suggest that brain sagging due
      to CSF hypovolemia impairs vestibular and vestibulocerebellar functions, which
      may cause dizziness and vertigo.

PMID- 25957210
TI  - [Magnetic Resonance Imaging Improvement in a Patient with Wilson's Disease
      Following Treatment with Trientine Hydrochloride and Zinc Acetate].
AB  - A 37-year-old male patient presented with psychiatric symptoms, dysarthria, limb
      dystonia, increased tendon reflexes, and a Kayser-Fleischer ring in his late
      teens. Laboratory examinations showed decreased concentrations of serum copper
      and ceruloplasmin, and increased urinary copper levels. Magnetic resonance
      imaging (MRI) showed high-signal-intensity lesions in the bilateral putamen,
      globus pallidus, thalamus, and brainstem on T2-weighted images (T2WI). Based on
      the MRI results and laboratory data, we diagnosed this patient with Wilson's
      disease (WD). He was treated with trientine hydrochloride and zinc acetate. Four
      months after the initiation of treatment, the patient'symptoms began to improve.
      On a follow-up MRI that was obtained 6 years after treatment, the high-signal
      intensity lesions on the T2WI had disappeared completely. However, the low-signal
      intensity lesions in the basal ganglia had spread to the caudate nuclei. Here, we
      discuss the characteristics of the MRI changes in WD following treatment. The
      Pathological basis for the low-signal-intensity lesions on T2WI in WD remains
      unclear. Our results suggest that this lesion may reflect the accumulation of
      materials other than copper.

PMID- 25957211
TI  - The rice transcription factor OsWRKY47 is a positive regulator of the response to
      water deficit stress.
AB  - OsWRKY47 is a divergent rice transcription factor belonging to the group II of
      the WRKY family. A transcriptomic analysis of the drought response of transgenic
      rice plants expressing P SARK ::IPT, validated by qPCR, indicated that OsWRKY47
      expression was induced under drought stress in P SARK ::IPT plants. A PCR
      assisted site selection assay (SELEX) of recombinant OsWRKY47 protein showed that
      the preferred sequence bound in vitro is (G/T)TTGACT. Bioinformatics analyses
      identified a number of gene targets of OsWRKY47; among these two genes encode a
      Calmodulin binding protein and a Cys-rich secretory protein. Using Oswrk47
      knockout mutants and transgenic rice overexpressing OsWRKY47 we show that the
      transcription of these putative targets were regulated by OsWRKY47. Phenotypic
      analysis carried out with transgenic rice plants showed that Oswrky47 mutants
      displayed higher sensitivity to drought and reduced yield, while plants
      overexpressing OsWRKY47 were more tolerant. 

PMID- 25957213
TI  - Synthesis of lemonose derivatives: methyl 4-amino-3-O,4-N-carbonyl-2,4,6-trideoxy
      3-C-methyl-alpha-l-lyxo-pyranoside and its phenyl thioglycoside.
AB  - Lemonose is a component of the antibiotic lemonomycin and other antibiotics and
      natural products. Three routes to the synthesis of the title compound, a
      protected, desmethyl derivative of lemonose, from l-rhamnose or its glycal, were
      investigated based on electrophilic cyclization, epoxidation-ring opening, and
      deoxygenation of an intermediate that was used in the synthesis of the amino
      sugar callipeltose. The deoxygenation route was successful and it provided the
      title compound, which was then converted to a phenyl thioglycoside. 

PMID- 25957214
TI  - Safety of clean urologic operations without prophylaxis antibiotic therapy in
      Cipto Mangunkusumo Hospital, Jakarta: A double-blind randomized controlled trial
      study.
AB  - OBJECTIVE: This study was conducted to identify the safety measures of performing
      clean urologic operations without administration of prophylaxis antibiotics.
      METHODS: We conducted a double-blind randomized controlled trial with patients
      who underwent clean urologic operations in Cipto Mangunkusumo Hospital, Jakarta,
      Indonesia, from April 2013 to January 2014. The local and systemic infection
      states were compared between the prophylaxis and placebo groups. Local infection
      was identified as surgical site infection and systemic infection as fever and
      leukocytosis. RESULTS: A total of 42 patients participated in the study (21
      patients in each group), comprising 14 (33.3%) children and 28 (66.7%) adults.
      The most frequently performed operation was surgical sperm retrieval. No patients
      in either group were found to have local or systemic infection. However, there
      was a statistical difference in the white blood cell counts between the two
      groups (p = 0.003), although there was no sign of local or systemic infection in
      any of the patients. CONCLUSION: Clean urologic operations without prophylaxis
      antibiotic therapy can be safely applied to urologic patients.

PMID- 25957215
TI  - Cardiomyocyte mitochondrial respiration is reduced by receptor for advanced
      glycation end-product signaling in a ceramide-dependent manner.
AB  - Cigarette smoke exposure is associated with an increased risk of cardiovascular
      complications. The role of advanced glycation end products (AGEs) is already well
      established in numerous comorbidities, including cardiomyopathy. Given the role
      of AGEs and their receptor, RAGE, in activating inflammatory pathways, we sought
      to determine whether ceramides could be a mediator of RAGE-induced altered heart
      mitochondrial function. Using an in vitro model, we treated H9C2 cardiomyocytes
      with the AGE carboxy-methyllysine before mitochondrial respiration assessment. We
      discovered that mitochondrial respiration was significantly impaired in AGE
      treated cells, but not when cotreated with myriocin, an inhibitor of de novo
      ceramide biosynthesis. Moreover, we exposed wild-type and RAGE knockout mice to
      secondhand cigarette smoke and found reduced mitochondrial respiration in the
      left ventricular myocardium from wild-type mice, but RAGE knockout mice were
      protected from this effect. Finally, conditional overexpression of RAGE in the
      lungs of transgenic mice elicited a robust increase in left ventricular ceramides
      in the absence of smoke exposure. Taken together, these findings suggest a RAGE
      ceramide axis as an important contributor to AGE-mediated disrupted cardiomyocyte
      mitochondrial function. 

PMID- 25957216
TI  - Reduced vascular responses to soluble guanylyl cyclase but increased sensitivity
      to sildenafil in female rats with type 2 diabetes.
AB  - Impaired nitric oxide (NO), soluble guanylyl cyclase (sGC), and cyclic guanosine
      monophosphate (cGMP) signaling (NO-sGC-cGMP) has been implicated in the
      pathogenesis of diabetic vascular dysfunction. Efforts to directly target this
      signaling have led to the development of sGC agonists that activate the heme
      group of sGC (stimulators) or preferentially activate sGC when the heme is
      oxidized (activators). In this study, we hypothesized that resistance arteries
      from female rats with spontaneous type 2 diabetes (Goto-Kakizaki rats, GK) would
      have reduced vasodilatory responses to heme-dependent sGC activation and
      increased responses to heme-independent sGC activation compared with control rats
      (Wistar). Endothelium-dependent and -independent relaxation was assessed in
      isolated segments from mesenteric resistance arteries (MA) mounted in a wire
      myograph. GK MA had reduced responses to acetylcholine (pEC50: 7.96 +/- 0.06 vs.
      7.66 +/- 0.05, P < 0.05) and sodium nitroprusside (pEC50: 8.34 +/- 0.05 vs. 7.77
      +/- 0.04, P < 0.05). There were no group differences in 8-bromoguanosine cGMP
      induced relaxation and protein kinase G1 expression (P > 0.05). GK MA had
      attenuated responses to BAY 41-2272 (heme-dependent sGC stimulator; pEC50: 7.56
      +/- 0.05 vs. 6.93 +/- 0.06, P < 0.05) and BAY 58-2667 (heme-independent sGC
      activator; pEC50: 10.82 +/- 0.07 vs. 10.27 +/- 0.08, P < 0.05) and increased
      sensitivity to sildenafil [phosphodiesterase 5 (PDE5) inhibitor; pEC50: 7.89 +/-
      0.14 vs. 8.25 +/- 0.13, P < 0.05]. Isolated resistance arteries from female rats
      of reproductive age that spontaneously develop type 2 diabetes have increased
      sensitivity to PDE5 inhibition and reduced responsiveness to sGC activators and
      stimulators.

PMID- 25957217
TI  - In vitro particulate matter exposure causes direct and lung-mediated indirect
      effects on cardiomyocyte function.
AB  - Particulate matter (PM) exposure induces a pathological response from both the
      lungs and the cardiovascular system. PM is capable of both manifestation into the
      lung epithelium and entrance into the bloodstream. Therefore, PM has the capacity
      for both direct and lung-mediated indirect effects on the heart. In the present
      studies, we exposed isolated rat cardiomyocytes to ultrafine particulate matter
      (diesel exhaust particles, DEP) and examined their contractile function and
      calcium handling ability. In another set of experiments, lung epithelial cells
      (16HBE14o- or Calu-3) were cultured on permeable supports that allowed access to
      both the basal (serosal) and apical (mucosal) media; the basal media was used to
      culture cardiomyocytes to model the indirect, lung-mediated effects of PM on the
      heart. Both the direct and indirect treatments caused a reduction in
      contractility as evidenced by reduced percent sarcomere shortening and reduced
      calcium handling ability measured in field-stimulated cardiomyocytes. Treatment
      of cardiomyocytes with various anti-oxidants before culture with DEP was able to
      partially prevent the contractile dysfunction. The basal media from lung
      epithelial cells treated with PM contained several inflammatory cytokines, and we
      found that monocyte chemotactic protein-1 was a key trigger for cardiomyocyte
      dysfunction. These results indicate the presence of both direct and indirect
      effects of PM on cardiomyocyte function in vitro. Future work will focus on
      elucidating the mechanisms involved in these separate pathways using in vivo
      models of air pollution exposure. 

PMID- 25957219
TI  - How to improve the overall quality of cardiac morphometric data.
AB  - By the mid-1990s, experts realized that drugs leading to improved ventricular
      remodeling were doing something remarkable in cardiac patients. The "age of
      cardiac remodeling" had begun. This created an experimental need for high-quality
      assessment of changes in cardiac tissue composition, including myocyte shape,
      myocardial fibrosis/collagen, and vascular remodeling. Many working in the field
      today have little or no training related to recognition of fixation artifacts or
      common errors associated with quantitative morphology. Unfortunately, such skills
      had become somewhat of a lost art during the ages of cardiac physiology in the
      mid-20th century and molecular biology, gaining prominence by the mid-1970s.
      Consequently, cardiac remodeling studies today are often seriously flawed to the
      point where data are not reproducible and subsequent researchers may be chasing
      the molecular basis of a nonexistent or erroneous phenotype. The current
      unacceptably high incidence of irreproducible data is a serious waste of time and
      resources as recently noted in comments by the National Institutes of Health
      director. The goal of this "how to" article is to share some lessons I have
      learned during nearly 40 years of assessing morphological changes in the heart.
      It is possible for any laboratory to routinely publish highly reproducible
      morphological data that stand the test of time and contribute to our fundamental
      knowledge of cardiac remodeling and the molecular mechanisms that drive it. 

PMID- 25957212
TI  - Do Surgeons Treat Their Patients Like They Would Treat Themselves?
AB  - BACKGROUND: There is substantial unexplained geographical and surgeon-to-surgeon
      variation in rates of surgery. One would expect surgeons to treat patients and
      themselves similarly based on best evidence and accounting for patient
      preferences. QUESTIONS/PURPOSES: (1) Are surgeons more likely to recommend
      surgery when choosing for a patient than for themselves? (2) Are surgeons less
      confident in deciding for patients than for themselves? METHODS: Two hundred
      fifty-four (32%) of 790 Science of Variation Group (SOVG) members reviewed 21
      fictional upper extremity cases (eg, distal radius fracture, De Quervain
      tendinopathy) for which surgery is optional answering two questions: (1) What
      treatment would you choose/recommend: operative or nonoperative? (2) On a scale
      from 0 to 10, how confident are you about this decision? Confidence is the degree
      that one believes that his or her decision is the right one (ie, most
      appropriate). Participants were orthopaedic, trauma, and plastic surgeons, all
      with an interest in treating upper extremity conditions. Half of the participants
      were randomized to choose for themselves if they had this injury or illness. The
      other half was randomized to make treatment recommendations for a patient of
      their age and gender. For the choice of operative or nonoperative, the overall
      recommendation for treatment was expressed as a surgery score per surgeon by
      dividing the number of cases they would operate on by the total number of cases
      (n = 21), where 100% is when every surgeon recommended surgery for every case.
      For confidence, we calculated the mean confidence for all 21 cases per surgeon;
      overall score ranges from 0 to 10 with a higher score indicating more confidence
      in the decision for treatment. RESULTS: Surgeons were more likely to recommend
      surgery for a patient (44.2% +/- 14.0%) than they were to choose surgery for
      themselves (38.5% +/- 15.4%) with a mean difference of 6% (95% confidence
      interval [CI], 2.1%-9.4%; p = 0.002). Surgeons were more confident in deciding
      for themselves than they were for a patient of similar age and gender (self: 7.9
      +/- 1.0, patient: 7.5 +/- 1.2, mean difference: 0.35 [CI, 0.075-0.62], p =
      0.012). CONCLUSIONS: Surgeons are slightly more likely to recommend surgery for a
      patient than they are to choose surgery for themselves and they choose for
      themselves with a little more confidence. Different perspectives, preferences,
      circumstantial information, and cognitive biases might explain the observed
      differences. This emphasizes the importance of (1) understanding patients'
      preferences and their considerations for treatment; (2) being aware that surgeons
      and patients might weigh various factors differently; (3) giving patients more
      autonomy by letting them balance risks and benefits themselves (ie, shared
      decision-making); and (4) assessing how dispassionate evidence-based decision
      aids help inform the patient and influences their decisional conflict. LEVEL OF
      EVIDENCE: Level III, diagnostic study.

PMID- 25957218
TI  - Sustained release nitrite therapy results in myocardial protection in a porcine
      model of metabolic syndrome with peripheral vascular disease.
AB  - Metabolic syndrome (MetS) reduces endothelial nitric oxide (NO) bioavailability
      and exacerbates vascular dysfunction in patients with preexisting vascular
      diseases. Nitrite, a storage form of NO, can mediate vascular function during
      pathological conditions when endogenous NO is reduced. The aims of the present
      study were to characterize the effects of severe MetS and obesity on
      dyslipidemia, myocardial oxidative stress, and endothelial NO synthase (eNOS)
      regulation in the obese Ossabaw swine (OS) model and to examine the effects of a
      novel, sustained-release formulation of sodium nitrite (SR-nitrite) on coronary
      vascular reactivity and myocardial redox status in obese OS subjected to critical
      limb ischemia (CLI). After 6 mo of an atherogenic diet, obese OS displayed a MetS
      phenotype. Obese OS had decreased eNOS functionality and NO bioavailability. In
      addition, obese OS exhibited increased oxidative stress and a significant
      reduction in antioxidant enzymes. The efficacy of SR-nitrite therapy was examined
      in obese OS subjected to CLI. After 3 wk of treatment, SR-nitrite (80 mg . kg(-1)
      . day(-1) bid po) increased myocardial nitrite levels and eNOS function.
      Treatment with SR-nitrite reduced myocardial oxidative stress while increasing
      myocardial antioxidant capacity. Ex vivo assessment of vascular reactivity of
      left anterior descending coronary artery segments demonstrated marked improvement
      in vasoreactivity to sodium nitroprusside but not to substance P and bradykinin
      in SR-nitrite-treated animals compared with placebo-treated animals. In
      conclusion, in a clinically relevant, large-animal model of MetS and CLI,
      treatment with SR-nitrite enhanced myocardial NO bioavailability, attenuated
      oxidative stress, and improved ex vivo coronary artery vasorelaxation.

PMID- 25957220
TI  - Increased superoxide production and altered nitric oxide-mediated relaxation in
      the aorta of young but not old male relaxin-deficient mice.
AB  - The vascular effects of exogenous relaxin (Rln) treatment are well established
      and include decreased myogenic reactivity and enhanced relaxation responses to
      vasodilators in small resistance arteries. These vascular responses are reduced
      in older animals, suggesting that Rln is less effective in mediating arterial
      function with aging. The present study investigated the role of endogenous Rln in
      the aorta and the possibility that vascular dysfunction occurs more rapidly with
      aging in Rln-deficient (Rln(-/-)) mice. We compared vascular function and
      underlying vasodilatory pathways in the aorta of male wild-type (Rln(+/+)) and
      Rln(-/-) mice at 4 and 16 mo of age using wire myography. Superoxide production,
      but not nitrotyrosine or NADPH oxidase expression, was significantly increased in
      the aorta of young Rln(-/-) mice, whereas endothelial nitric oxide (NO) synthase
      and basal NO availability were both significantly decreased compared with
      Rln(+/+) mice. In the presence of the cyclooxygenase inhibitor indomethacin,
      sensitivity to ACh was significantly decreased in young Rln(-/-) mice,
      demonstrating altered NO-mediated relaxation that was normalized in the presence
      of a membrane-permeable SOD or ROS scavenger. These vascular phenotypes were not
      exacerbated in old Rln(-/-) mice and, in most cases, did not differ significantly
      from old Rln(+/+) mice. Despite the vascular phenotypes in Rln(-/-) mice,
      endothelium-dependent and -independent vasodilation were not adversely affected.
      Our data show a role for endogenous Rln in reducing superoxide production and
      maintaining NO availability in the aorta but also demonstrate that Rln deficiency
      does not compromise vascular function in this artery or exacerbate endothelial
      dysfunction associated with aging. 

PMID- 25957222
TI  - Effects of milrinone and epinephrine or dopamine on biventricular function and
      hemodynamics in an animal model with right ventricular failure after pulmonary
      artery banding.
AB  - Right ventricular (RV) failure due to chronic pressure overload is a main
      determinant of outcome in congenital heart disease. Medical management is
      challenging because not only contractility but also the interventricular
      relationship is important for increasing cardiac output. This study evaluated the
      effect of milrinone alone and in combination with epinephrine or dopamine on
      hemodynamics, ventricular performance, and the interventricular relationship. RV
      failure was induced in 21 Danish landrace pigs by pulmonary artery banding. After
      10 wk, animals were reexamined using biventricular pressure-volume conductance
      catheters. The maximum pressure in the RV increased by 113% (P < 0.0001) and end
      diastolic volume by 43% (P < 0.002), while left ventricular (LV) pressure
      simultaneously decreased (P = 0.006). Concomitantly, mean arterial pressure (MAP;
      -16%, P = 0.01), cardiac index (CI; -23%, P < 0.0001), and mixed venous oxygen
      saturation (SvO2 ; -40%, P < 0.0001) decreased. Milrinone increased CI (11%, P =
      0.008) and heart rate (HR; 21%, P < 0.0001). Stroke volume index (SVI) decreased
      (7%, P = 0.03), although RV contractility was improved. The addition of either
      epinephrine or dopamine further increased CI and HR in a dose-dependent manner
      but without any significant differences between the two interventions. A more
      pronounced increase in biventricular contractility was observed in the dopamine
      treated animals. LV volume was reduced in both the dopamine and epinephrine
      groups with increasing doses In the failing pressure overloaded RV, milrinone
      improved CI and increased contractility. Albeit additional dose-dependent effects
      of both epinephrine and dopamine on CI and contractility, neither of the
      interventions improved SVI due to reduced filling of the LV. 

PMID- 25957221
TI  - GABA and glycine receptors in the nucleus ambiguus mediate tachycardia elicited
      by chemical stimulation of the hypothalamic arcuate nucleus.
AB  - We have previously reported that stimulation of the hypothalamic arcuate nucleus
      (ARCN) by microinjections of N-methyl-d-aspartic acid (NMDA) elicits tachycardia,
      which is partially mediated via inhibition of vagal inputs to the heart. The
      neuronal pools and neurotransmitters in them mediating tachycardia elicited from
      the ARCN have not been identified. We tested the hypothesis that the tachycardia
      elicited from the ARCN may be mediated by inhibitory neurotransmitters in the
      nucleus ambiguus (nAmb). Experiments were done in urethane-anesthetized,
      artificially ventilated, male Wistar rats. In separate groups of rats, unilateral
      and bilateral microinjections of muscimol (1 mM), gabazine (0.01 mM), and
      strychnine (0.5 mM) into the nAmb significantly attenuated tachycardia elicited
      by unilateral microinjections of NMDA (10 mM) into the ARCN. Histological
      examination of the brains showed that the microinjections sites were within the
      targeted nuclei. Retrograde anatomic tracing from the nAmb revealed direct
      bilateral projections from the ARCN and hypothalamic paraventricular nucleus to
      the nAmb. The results of the present study suggest that tachycardia elicited by
      stimulation of the ARCN by microinjections of NMDA is mediated via GABAA and
      glycine receptors located in the nAmb. 

PMID- 25957226
TI  - Working with uncertainty: A grounded theory study of health-care professionals'
      experiences of working with children and adolescents with chronic fatigue
      syndrome.
AB  - This grounded theory study explores conceptualisations of chronic fatigue
      syndrome/myalgic encephalomyelitis from semi-structured interviews with 10 health
      care professionals working with children and adolescents. The findings suggest
      that a lack of a clear empirical understanding of chronic fatigue
      syndrome/myalgic encephalomyelitis leads to 'working with uncertainty', whereby
      health-care professionals utilise previous experiences to make sense of the
      condition and inform their clinical practice. How health-care professionals make
      sense of chronic fatigue syndrome/myalgic encephalomyelitis may influence the
      labels given to young people and the interventions they receive. The findings
      provide insight into a currently understudied area, and highlight potential
      avenues for further research and clinical practice.

PMID- 25957224
TI  - Clopidogrel With Aspirin in Acute Minor Stroke or Transient Ischemic Attack
      (CHANCE) Trial: One-Year Outcomes.
AB  - BACKGROUND: The Clopidogrel in High-risk patients with Acute Non-disabling
      Cerebrovascular Events (CHANCE) trial showed that the combined treatment of
      clopidogrel and aspirin decreases the 90-day risk of stroke without increasing
      hemorrhage in comparison with aspirin alone, but provided insufficient data to
      establish whether the benefit persisted over a longer period of time beyond the
      trial termination. We report the 1-year follow-up outcomes of this trial. METHODS
      AND RESULTS: The trial was a randomized, double-blind, placebo-controlled trial
      conducted at 114 centers in China. We randomly assigned 5170 patients within 24
      hours after onset of minor stroke or high-risk transient ischemic attack to
      clopidogrel-aspirin therapy (loading dose of 300 mg of clopidogrel on day 1,
      followed by 75 mg of clopidogrel per day for 90 days, plus 75 mg of aspirin per
      day for the first 21 days) or to the aspirin-alone group (75 mg/d for 90 days).
      The primary outcome was stroke event (ischemic or hemorrhagic) during 1-year
      follow-up. Differences in outcomes between groups were assessed by using the Cox
      proportional hazards model. Stroke occurred in 275 (10.6%) patients in the
      clopidogrel-aspirin group, in comparison with 362 (14.0%) patients in the aspirin
      group (hazard ratio, 0.78; 95% confidence interval, 0.65-0.93; P=0.006). Moderate
      or severe hemorrhage occurred in 7 (0.3%) patients in the clopidogrel-aspirin
      group and in 9 (0.4%) patients in the aspirin group (P=0.44). CONCLUSIONS: The
      early benefit of clopidogrel-aspirin treatment in reducing the risk of subsequent
      stroke persisted for the duration of 1-year of follow-up. CLINICAL TRIAL
      REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589.

PMID- 25957223
TI  - (In)activity-related neuroplasticity in brainstem control of sympathetic outflow:
      unraveling underlying molecular, cellular, and anatomical mechanisms.
AB  - More people die as a result of physical inactivity than any other preventable
      risk factor including smoking, high cholesterol, and obesity. Cardiovascular
      disease, the number one cause of death in the United States, tops the list of
      inactivity-related diseases. Nevertheless, the vast majority of Americans
      continue to make lifestyle choices that are creating a rapidly growing burden of
      epidemic size and impact on the United States healthcare system. It is imperative
      that we improve our understanding of the mechanisms by which physical inactivity
      increases the incidence of cardiovascular disease and how exercise can prevent or
      rescue the inactivity phenotype. The current review summarizes research on
      changes in the brain that contribute to inactivity-related cardiovascular
      disease. Specifically, we focus on changes in the rostral ventrolateral medulla
      (RVLM), a critical brain region for basal and reflex control of sympathetic
      activity. The RVLM is implicated in elevated sympathetic outflow associated with
      several cardiovascular diseases including hypertension and heart failure. We
      hypothesize that changes in the RVLM contribute to chronic cardiovascular disease
      related to physical inactivity. Data obtained from our translational rodent
      models of chronic, voluntary exercise and inactivity suggest that functional,
      anatomical, and molecular neuroplasticity enhances glutamatergic
      neurotransmission in the RVLM of sedentary animals. Collectively, the evidence
      presented here suggests that changes in the RVLM resulting from sedentary
      conditions are deleterious and contribute to cardiovascular diseases that have an
      increased prevalence in sedentary individuals. The mechanisms by which these
      changes occur over time and their impact are important areas for future study. 

PMID- 25957227
TI  - Effect of perceived stress on depression of Chinese "Ant Tribe" and the
      moderating role of dispositional optimism.
AB  - This study examines the moderating role of dispositional optimism on the
      relationship between perceived stress and depression of the Chinese "Ant Tribe."
      A total of 427 participants from an Ant Tribe community completed the measures of
      perceived stress, optimism, and depression. The structural equation modeling
      (SEM) analysis showed that dispositional optimism moderated the association
      between perceived stress and depression. The Ant Tribe with high perceived stress
      reported higher scores in depression than those with low perceived stress at low
      dispositional optimism level. However, the impact of perceived stress on
      depression was insignificant in the high dispositional optimism group.

PMID- 25957228
TI  - A systematic review of the effectiveness of interventions using the Common Sense
      Self-Regulatory Model to improve adherence behaviours.
AB  - This systematic review assessed the effectiveness of the Common Sense Self
      Regulatory Model in the design of interventions to improve adherence behaviours.
      Of nine eligible studies, six reported improvements in adherence behaviours and
      three showed moderate to large effects on return to work and lifestyle
      recommendations. Four studies stated how Common Sense Self-Regulatory Model
      constructs were addressed in the intervention and five measured illness
      perceptions as outcomes. Evidence was found for targeting cure/control
      perceptions in studies aimed at improving adherence behaviours. Future studies
      need to measure illness perceptions pre- and post-intervention to enable
      mediational analyses to assess the effect of Common Sense Self-Regulatory Model
      interventions on improving health outcomes.

PMID- 25957225
TI  - CD11c+ Dendritic Cells Accelerate the Rejection of Older Cardiac Transplants via
      Interleukin-17A.
AB  - BACKGROUND: Organ transplantation has seen an increased use of organs from older
      donors over the past decades in an attempt to meet the globally growing shortage
      of donor organs. However, inferior transplantation outcomes when older donor
      organs are used represent a growing challenge. METHODS AND RESULTS: Here, we
      characterize the impact of donor age on solid-organ transplantation using a
      murine cardiac transplantation model. We found a compromised graft survival when
      older hearts were used. Shorter graft survival of older hearts was independent of
      organ age per se, because chimeric young or old organs repopulated with young
      passenger leukocytes showed comparable survival times. Transplantation of older
      organs triggered more potent alloimmune responses via intragraft CD11c+ dendritic
      cells augmenting CD4+ and CD8+ T-cell proliferation and proinflammatory cytokine
      production, particularly that of interleukin-17A. Of note, depletion of donor
      CD11c+ dendritic cells before engraftment, neutralization of interleukin-17A, or
      transplantation of older hearts into IL-17A(-/-) mice delayed rejection and
      reduced alloimmune responses to levels observed when young hearts were
      transplanted. CONCLUSIONS: These results demonstrate a critical role of old donor
      CD11c+ dendritic cells in mounting age-dependent alloimmune responses with an
      augmented interleukin-17A response in recipient animals. Targeting interleukin
      17A may serve as a novel therapeutic approach when older organs are transplanted.

PMID- 25957229
TI  - Deletion of the gene for adiponectin accelerates diabetic nephropathy in the Ins2
      (+/C96Y) mouse.
AB  - AIMS/HYPOTHESIS: Diabetic nephropathy is one of the most common forms of chronic
      kidney disease. The role of adiponectin in the development of diabetic
      nephropathy has not been elucidated, and the aim of the present study was to
      investigate the hypothesis that deletion of the gene for adiponectin would
      accelerate diabetic nephropathy in the Akita mouse. METHODS: We followed four
      groups of mice from 4 weeks to 16 weeks of age (n >= 10 in each group): wild-type
      (WT) (Ins2 (+/+) Adipoq(+/+)) mice; APN(-/-) (Ins2(+/+) Adipoq(-/-)) mice; Akita
      (Ins2(+/C96Y) Adipoq(+/+)) mice and Akita/APN(-/-) (Ins2(+/C96Y) Adipoq(-/-))
      mice. The mice were then killed and diabetic kidney injury was assessed. In vitro
      experiments were performed in primary mesangial cells. RESULTS: Mice from both
      diabetic groups exhibited increased glomerular adiponectin receptor 1 (adipoR1)
      expression, kidney hypertrophy, glomerular enlargement, increased albuminuria and
      tissue oxidative stress compared with the WT control. Deletion of the adiponectin
      gene had no effect on glycaemia. However, Akita/APN(-/-) mice exhibited a greater
      extent of renal hypertrophy. In vitro, adiponectin attenuated high-glucose
      induced phosphorylation of mammalian target of rapamycin (mTOR) and ribosomal
      protein S6 kinase (S6K). A higher level of fibrosis was observed in the
      tubulointerstitial and glomerular compartments of the Akita/APN(-/-) mice and
      adiponectin was found to inhibit TGFbeta-induced Smad2 and Smad3 phosphorylation
      in vitro. There was an exaggerated inflammatory response in the Akita/APN(-/-)
      mice. Adiponectin also inhibited high-glucose-induced activation of nuclear
      factor kappaB (NFkappaB) in mesangial cells. CONCLUSIONS/INTERPRETATION: Our data
      suggest that adiponectin is an important determinant of the kidney response to
      high glucose in vivo and in vitro.

PMID- 25957230
TI  - The future of brown adipose tissues in the treatment of type 2 diabetes.
AB  - The recent recognition that humans possess active depots of brown adipose tissue
      has boosted the interest in this tissue as a potential target for the prevention
      and treatment of obesity and related metabolic disorders. Furthermore, it was
      also revealed that brown adipose tissue (BAT) in humans may consist of so-called
      beige or brite adipocytes. So far, cold exposure is recognised as the strongest
      activator of BAT in humans, but there is much ongoing research focused on finding
      alternative activators of BAT. The consequences of long-term BAT activation
      and/or cold exposure on metabolic health are still unknown, and this represents
      an area of intensive research. This is one of a series of commentaries under the
      banner '50 years forward', giving personal opinions on future perspectives in
      diabetes, to celebrate the 50th anniversary of Diabetologia (1965-2015).

PMID- 25957231
TI  - A model for the role of gut bacteria in the development of autoimmunity for type
      1 diabetes.
AB  - Several lines of evidence suggest a role for the gut microbiome in type 1
      diabetes. Treating diabetes-prone rodents with probiotics or antibiotics prevents
      the development of the disorder. Diabetes-prone rodents also have a distinctly
      different gut microbiome compared with healthy rodents. Recent studies in
      children with a high genetic risk for type 1 diabetes demonstrate significant
      differences in the gut microbiome between children who develop autoimmunity for
      the disease and those who remain healthy. However, the differences in microbiome
      composition between autoimmune and healthy children are not consistent across all
      studies because of the strong environmental influences on microbiome composition,
      particularly diet and geography. Controlling confounding factors of microbiome
      composition uncovers bacterial associations with disease. For example, in a human
      cohort from a single Finnish city where geography is confined, a strong
      association between one dominant bacterial species, Bacteroides dorei, and type 1
      diabetes was discovered (Davis-Richardson et al. Front Microbiol 2014;5:678).
      Beyond this, recent DNA methylation analyses suggest that a thorough epigenetic
      analysis of the gut microbiome may be warranted. These studies suggest a testable
      model whereby a diet high in fat and gluten and low in resistant starch may be
      the primary driver of gut dysbiosis. This dysbiosis may cause a lack of butyrate
      production by gut bacteria, which, in turn, leads to the development of a
      permeable gut followed by autoimmunity. The bacterial community responsible for
      these changes in butyrate production may vary around the world, but bacteria of
      the genus Bacteroides are thought to play a key role. 

PMID- 25957232
TI  - Comparison of HOMA-IR, HOMA-beta% and disposition index between US white men and
      Japanese men in Japan in the ERA JUMP study: was the calculation of disposition
      index legitimate? Reply to Yamauchi K, Sato Y, Nakasone Y et al [letter].

PMID- 25957233
TI  - Transcript profiling of aquaporins during basidiocarp development in Laccaria
      bicolor ectomycorrhizal with Picea glauca.
AB  - Sporocarp formation is part of the reproductive stage in the life cycle of many
      mycorrhizal macrofungi. Sporocarp formation is accompanied by a transcriptomic
      switch and profound changes in regulation of the gene families that play crucial
      roles in the sporocarp initiation and maturation. Since sporocarp growth requires
      efficient water delivery, in the present study, we investigated changes in
      transcript abundance of six fungal aquaporin genes that could be cloned from the
      ectomycorrhizal fungus Laccaria bicolor strain UAMH8232, during the initiation
      and development of its basidiocarp. Aquaporins are intrinsic membrane proteins
      facilitating the transmembrane transport of water and other small neutral
      molecules. In controlled-environment experiments, we induced basidiocarp
      formation in L. bicolor, which formed ectomycorrhizal associations with white
      spruce (Picea glauca) seedlings. We profiled transcript abundance corresponding
      to six fungal aquaporin genes at six different developmental stages of
      basidiocarp growth and development. We also compared physiological parameters of
      non-inoculated to mycorrhizal seedlings with and without the presence of
      basidiocarps. Two L. bicolor aquaporins--JQ585592, a functional channel for CO2,
      NO and H2O2, and JQ585595, a functional water channel--showed the greatest degree
      of upregulation during development of the basidiocarp. Our findings point to the
      importance of aquaporin-mediated transmembrane water and CO2 transport during
      distinct stages of basidiocarp development.

PMID- 25957234
TI  - Colonic polyposis syndromes--an experience from a tertiary centre in South India.
AB  - BACKGROUND: Several polyposis syndromes of the gastrointestinal tract have been
      recognized which carry increased risk for cancer and have a genetic
      predisposition. There is a paucity of literature regarding the occurrence and the
      burden of colonic polyposis syndromes in the Indian subcontinent. This study
      attempts to highlight this hitherto unaddressed burden and the associated
      increased risk for inherited colonic cancer in this geographical location.
      METHODS: A retrospective study of various colonic polyposis syndromes encountered
      at a tertiary centre in South India over a period of 8 years (2005 to 2012) was
      performed. The diagnosis in each case was made histologically with
      clinicopathological correlation. RESULTS: Fifty cases were identified as
      belonging to a colonic polyposis syndrome, during the study period. There were 27
      males and 23 females with a median age of 36.5 years (range 19 months to 78
      years). The commonest syndrome was familial adenomatous polyposis (n = 27; 54 %)
      followed by Peutz-Jeghers syndrome (n = 11), attenuated familial adenomatous
      polyposis (n = 7), juvenile polyposis syndrome (n = 3), hyperplasic polyposis
      syndrome (n = 1) and Cronkhite-Canada syndrome (n = 1). Colonic malignancy was
      documented at first presentation in 22 patients (44 %). CONCLUSIONS: Our study
      highlights the various colonic polyposis syndromes encountered in a tertiary care
      institution in Southern India.

PMID- 25957235
TI  - Surface activity and flocculation behavior of polyethylene glycol-functionalized
      silica nanoparticles.
AB  - Colloidal silica nanoparticles have been functionalized with methyl polyethylene
      glycol silane (mPEG silane) and the PEGylated particles have been characterized
      with focus on exploring their surface chemical properties. The degree of surface
      functionalization was quantified using NMR diffusometry, and the measurements
      showed that the silane binds covalently to the silica surface. Samples with
      surface coverages ranging from 0.068 to 0.315 MUmol silane/m(2) have been
      analyzed. The functionalized particles proved to be surface active and showed a
      significant reduction in surface charge and zeta potential with increasing degree
      of PEG functionalization. All samples showed colloidal stability at neutral pH
      and above within the range studied. At lower pH, the samples with low surface
      coverage displayed a reversible flocculation behavior, while samples with a high
      surface coverage and samples without functionalization remained stable. This
      suggests that steric stabilization is effective at low pH when the surface
      coverage is high enough; electrostatic stabilization is effective for samples
      without functionalization; and that inter-particle PEG-silica interactions cause
      flocculation of particles with too low degrees of PEG functionalization.

PMID- 25957236
TI  - DNA-modulated photo-transformation of AgCl to silver nanoparticles: visiting the
      formation mechanism.
AB  - Solution-phase synthesis and post-synthetic bio-modification have continued to
      play a dominant role in preparation of nanostructured biomaterials. Heterogeneous
      nucleation and growth that occur much more often in nature, however, remain
      rarely explored in nano-biomaterials research. We have newly developed a DNA
      modulated photoconversion approach to uniform silver nanoparticles that afford
      DNA-directed recognition and multi-mode imaging. The present study was aimed at
      understanding the rapid heterogeneous nucleation and growth of AgNPs at the solid
      liquid interface with the aid of DNA. Dynamic changes in absorbance, size and
      morphology of silver nanostructures were monitored and analyzed to clarify the
      growth kinetics, which indicated a synthetic route involving synchronous growth
      of silver nanostructures and the fragmentation and consumption of AgCl. Various
      stabilizers, including polymer and amino acids, were assessed and compared with
      respect to the efficacy in photoconversion of AgCl. DNA was found to offer the
      best monodispersity and the smallest diameter for the resultant AgNPs, due to its
      strong interactions to silver species as well as excellent charge dispersion
      ability. By controlling the physicochemical property of DNA through choice of pH
      and ionic strength, we have demonstrated tunable structure and composition of the
      nanoparticles. 

PMID- 25957237
TI  - Molecular mechanisms of the impact of smoke-oxidants.
AB  - Tobacco smoke is a source of many xenobiotics and free radicals. Reactive oxygen
      species can affect the body both directly and indirectly, through the activation
      of both signalling pathways and transcription factors (NF-kappaB and AP-1). One
      of the most important signalling cascades which can affect the oxidants in smoke
      are mitogen-activated protein kinases (MAPK). The mechanism of MAPK pathways
      activation by reactive oxygen species depends on the stimulation of specific
      tyrosine kinases and protein tyrosine phosphatases inactivation. An activated MAP
      protein can initiate AP-1 signalling and interact with many other transcription
      factors. The components of tobacco smoke with oxidation-reduction properties can
      have an effect on NF-kappaB signalling. Binding of NF-kappaB and AP-1 with DNA is
      a complicated process, in which coactivators exhibiting internal histone
      acetyltransferase activity are involved. The balance between histone deacetylases
      and acetylases is important for the regulation of inflammatory response in the
      lungs. Tobacco smoke causes increased acetylase activity and decreased
      deacetylase activity in epithelial lung cells. The result is an increase in the
      activation of NF-kappaB and AP-1. Oxygen free radicals from tobacco smoke can
      change the redox status of cells, which can in turn induce the activation of
      transcription factors, chromatin remodelling and intensified genes transcription
      for inflammatory mediators. 

PMID- 25957238
TI  - Salvaging an implant with damaged internal threads.

PMID- 25957239
TI  - In vitro evaluation of accuracy and precision of automated robotic tooth
      preparation system for porcelain laminate veneers.
AB  - STATEMENT OF PROBLEM: Controlling tooth reduction for porcelain laminate veneers
      (PLVs) in fractions of millimeters is challenging. PURPOSE: The purpose of this
      study was to assess an automated robotic tooth preparation system for PLVs for
      accuracy and precision compared with conventional freehand tooth preparation.
      MATERIAL AND METHODS: Twenty maxillary central incisor tooth models were divided
      into 2 groups. Ten were assigned to a veneer preparation with a robotic arm
      according to preoperative preparation design-specific guidelines (experimental
      group). Ten were assigned to conventional tooth preparation by a clinician
      (control group). Initially, all tooth models were scanned with a 3- dimensional
      (3D) laser scanner, and a tooth preparation for PLVs was designed on a 3D image.
      Each tooth model was attached to a typodont. For the experimental group, an
      electric high-speed handpiece with a 0.9-mm-diameter round diamond rotary cutting
      instrument was mounted on the robotic arm. The teeth were prepared automatically
      according to the designed image. For the control group, several diamond rotary
      cutting instruments were used to prepare the tooth models according to
      preoperative preparation design guidelines. All prepared tooth models were
      scanned. The preoperative preparation design image and scanned postoperative
      preparation images were superimposed. The dimensional difference between those 2
      images was measured on the facial aspect, finish line, and incisal edge.
      Differences between the experimental and the control groups from the 3D design
      image were computed. Accuracy and precision were compared for all sites and
      separately for each tooth surface (facial, finish line, incisal). Statistical
      analyses were conducted with a permutation test for accuracy and with a modified
      robust Brown-Forsythe Levene-type test for precision (alpha=.05). RESULTS: For
      accuracy for all sites, the mean absolute deviation was 0.112 mm in the control
      group and 0.133 mm in the experimental group. No significant difference was found
      between the 2 (P=.15). For precision of all sites, the standard deviation was
      0.141 mm in the control group and 0.185 mm in the experimental group. The
      standard deviation in the control group was significantly lower (P=.030). In
      terms of accuracy for the finish line, the control group was significantly less
      accurate (P=.038). For precision, the standard deviation in the control group was
      significantly higher at the finish line (P=.034). CONCLUSIONS: For the data from
      all sites, the experimental procedure was able to prepare the tooth model as
      accurately as the control, and the control procedure was able to prepare the
      tooth model with better precision. The experimental group showed better accuracy
      and precision at the finish line.

PMID- 25957240
TI  - Influence of CAD/CAM tool and material on tool wear and roughness of dental
      prostheses after milling.
AB  - STATEMENT OF PROBLEM: Computer-aided design/computer-aided manufacturing
      (CAD/CAM) machining influences the surface roughness of dental restorations and
      tool wear. Roughness must be suitable to meet clinical requirements, and the tool
      must last as long as possible. PURPOSE: The purpose of this pilot study was to
      investigate the influence of the CAD/CAM tool-material couple on tool wear and
      surface roughness after milling. MATERIAL AND METHODS: Three tools (Lyra conical
      tool O1 mm; GACD SASU, Lyra conical tool O1.05 mm; GACD SASU, and Cerec cylinder
      pointed tool 12S; Sirona Dental Systems GmbH) and 3 CAD/CAM materials (Lava
      Ultimate; 3M ESPE, Mark II; VITA Zahnfabrik H. Rauter GmbH, and Enamic; VITA
      Zahnfabrik H. Rauter GmbH) were tested. The tool wear of 6 tool-material couples
      at a feed rate of 2 m/min was analyzed before and after 8 minutes of flank and
      climb milling with optical and scanning electron microscopy (SEM) observations
      and tool weighing. The surface roughness after milling was observed for 9 tool
      material couples for flank and climb milling. Feed rates of 1, 2, 3, and 4.8
      m/min were used for each couple. Ra, Rt, Rz, Sa, Sq, and Sz roughness criteria
      were measured. A paired comparison of tool-material couples was conducted with
      the Kruskal-Wallis test. RESULTS: The Mark II material led to more severe tool
      wear. Milling of Lava Ultimate resulted in chip deposits on the tool grit. The
      Cerec cylinder pointed tool 12S was less worn for each material tested. The Cerec
      cylinder pointed tool 12S and the Lyra conical tool O1.05 mm provided similar
      roughness measurements for the 3 materials tested. The Lyra conical tool O1.05 mm
      tool provided better roughness than the Lyra conical tool O1 mm tool for the
      Enamic material. CONCLUSION: Tool lifetime calculated by volume of milled
      material removed should be the measure provided by CAD/CAM manufacturers instead
      of a number of blocks. This tool lifetime should be provided for the milling
      conditions associated with the material milled. Material hardness and tool grit
      are key factors for achieving a given roughness.

PMID- 25957241
TI  - Effect of simulated mastication on the surface roughness of three ceramic
      systems.
AB  - STATEMENT OF PROBLEM: Zirconia complete coverage crowns are being widely used as
      restorations because of their high strength and improved esthetics. Data are
      sparse about the change in surface roughness of this ceramic material after
      repeated mastication cycles of opposing enamel. PURPOSE: The purpose of this
      study was to investigate changes in the surface roughness after being subjected
      to 3-body wear-opposing human enamel of 3 types of ceramics: dense sintered
      yttrium-stabilized zirconia (Z); lithium disilicate (L); and a conventional low
      fusing feldspathic porcelain (P) treated to impart a rough, smooth, or glazed
      surface. MATERIAL AND METHODS: Twenty-four specimens of each of the Z and L
      ceramic were sectioned from computer-aided design and computer-aided
      manufacturing blocks into rectangular plates (15*12*2 mm). Twenty-four specimens
      of the feldspathic porcelain were formed into disks (12-mm diameter) from powders
      compressed in a silicone mold. All specimens (n=72) were prepared according to
      the manufacturers' recommendations. Specimens of each ceramic group were placed
      into 1 of 3 groups: group R, rough surface finish; group S, smooth surface
      finish; and group G, glazed surface finish. A total of 72 specimens (9 groups
      with 8 specimens each) was placed in a 3-body wear simulator, with standardized
      enamel specimens (n=72) acting as the substrate. The changes in surface roughness
      of the ceramic specimens were evaluated after 50,000 cycles. Data were analyzed
      by a repeated measures 3-way ANOVA mixed procedure with the Satterthwaite method
      for degrees of freedom and maximum likelihood estimation of the covariance
      parameters (alpha=.05). RESULTS: Data showed that the PS group exhibited the
      largest change in surface roughness, becoming significantly rougher (P<.004). The
      LR group became significantly smoother (P=.012). CONCLUSIONS: The surfaces of
      monolithic zirconia ceramic and lithium disilicate did not become as rough as the
      surface of conventional feldspathic porcelain after enamel wear.

PMID- 25957242
TI  - Impact of lateral occlusion schemes: A systematic review.
AB  - STATEMENT OF PROBLEM: Although several lateral occlusion philosophies have been
      proposed in the literature, there is a lack of compelling evidence supporting any
      scheme. PURPOSE: The purpose of this systematic review was to investigate the
      clinical implications of different lateral occlusion schemes. MATERIAL AND
      METHODS: A literature search was completed through PubMed (MEDLINE), Google
      Scholar, and Cochrane Library, up to January 2014. The literature search aimed to
      retrieve 2 study categories: group 1: comparative studies; group 2: clinical
      outcome studies. The inclusion criteria were peer-reviewed human clinical studies
      published in English. The search was further supplemented by manual searching
      through the reference lists of the selected studies. RESULTS: The initial search
      revealed a total of 680 studies; however, after applying the inclusion criteria,
      26 studies were found suitable for the analysis (13 for group 1 and 13 for group
      2). The most commonly evaluated lateral occlusion schemes were canine-guided
      occlusion (CGO) and group function occlusion (GFO). Group 1 studies evaluated the
      impact of lateral occlusion schemes on muscular electromyographic (EMG) activity,
      condylar displacement, mastication, and mandibular movement. Group 2 studies
      evaluated the impact of restored occlusion on longevity, patient comfort, and
      pathologic consequences. CGO was associated with narrower mastication and less
      EMG activity of the masticatory muscles during clenching. GFO was associated with
      wider mandibular movement and quicker mastication. During mastication, there was
      no difference in EMG activity between the 2 lateral occlusion schemes.
      Furthermore, the long-term studies indicated that there is no difference between
      the 2 schemes in patient comfort and restoration longevity. CONCLUSION: Although
      there are immediate differences between the different lateral occlusion schemes,
      patients have the capability to successfully adapt to CGO or GFO.

PMID- 25957243
TI  - Degradation of abamectin by newly isolated Stenotrophomonas maltophilia ZJB-14120
      and characterization of its abamectin-tolerance mechanism.
AB  - An abamectin (ABM)-degrading bacterium, Stenotrophomonas maltophilia ZJB-14120,
      was isolated and identified. This strain is capable of degrading 84.82% of ABM at
      an initial concentration of 200 mg/L over a 48 h incubation period. This strain
      showed efficient biodegradation ability (7.81 mg/L/h) to ABM and high tolerance
      (1000 mg/L) to all macrolides tested. In addition to ABM, emamectin, erythromycin
      and spiramycin can also be degraded by this strain. Modifications involving
      either reduction of the double bond between C22-C23 or replacement of the C25
      group of ABM with a cyclohexyl group can completely inhibit biodegradation of
      ABM. The ABM-degrading capability of strain ZJB-14120 is likely to be intrinsic
      to its metabolism and could be inhibited by incubating with erythromycin,
      azithromycin, spiramycin or rifampicin. A new and successive degradation pathway
      was proposed based on metabolite analysis. Although there is evidence for
      metabolite inhibition, this strain has high ABM degradation activity and
      reusability. Further investigation showed that activated macrolide efflux pump(s)
      and an undetermined mechanism for regulating the intracellular ABM concentration
      are responsible for normal uptake of essential metabolites while pumping out
      excess harmful compounds. Strain ZJB-14120 may provide efficient treatment of
      water and soil contaminated by toxic levels of abamectin and emamectin. 

PMID- 25957244
TI  - Genetic characterization and expression of leucocin B, a class IId bacteriocin
      from Leuconostoc carnosum 4010.
AB  - Leuconostoc carnosum 4010 is an antimicrobial strain used as a protective culture
      in vacuum-packed meats. In this study, we showed that, in addition to
      antilisterial class IIa bacteriocins leucocin A and C, the strain also produces
      class IId bacteriocin leucocin B, the antimicrobial activity of which is limited
      to the genera Leuconostoc and Weissella. Two novel genes, lebBI encoding the
      leucocin B precursor with a double-glycine-type leader and putative immunity
      protein LebI, were identified on L. carnosum 4010 plasmid pLC4010-1. LebI
      contains three transmembrane spans and shares 55% identity with the mesentericin
      B105 immunity protein. Genes lebBI were shown to be transcribed in 4010 by RT-PCR
      analysis. The secretion of leucocin B in L. carnosum 4010 was shown by spot-on
      lawn and SDS-gel overlay methods with a Leuconostoc strain sensitive to leucocin
      B but resistant to leucocins A and C. In addition, leucocins A and B from L.
      carnosum 4010 were cloned as SSusp45 fusions in heterologous host Lactococcus
      lactis and the secretion of active bacteriocins was detected on indicator plates.

PMID- 25957245
TI  - [Sleep disorders in dementia patients].
AB  - Dementia is characterized by cognitive and also behavioral and psychological
      symptoms of dementia (BPSD). The most prominent BPSD are depression and apathy
      but sleep disorders also complicate the clinical course of dementia. These
      symptoms are a severe burden for patients and caregivers and are difficult to
      treat partly due to comorbidities. Common sleep disorders in dementia are
      insomnia, hypersomnia, circadian rhythm alterations and aberrant nocturnal motor
      behavior. Sleep duration and rapid eye movement (REM) sleep are reduced. The
      diagnostic assessment of sleep disorders should include an evaluation of the
      underlying risk factors and a detailed sleep history for which several assessment
      instruments are available. The therapy of sleep disorders of dementia is
      primarily nonpharmacological: sleep counseling, sleep hygiene regulation,
      relaxation and psychotherapy techniques are given priority. Pharmacological
      treatment often has severe side effects in this elderly, vulnerable population
      and can only be considered if other nonpharmacological options have been
      unsuccessful. The application of medication should be limited in time and dosage.
      The pharmacological therapeutic options are critically discussed in detail. 

PMID- 25957246
TI  - [Risk scores for community acquired pneumonia in elderly and geriatric patients].
AB  - BACKGROUND: Community-acquired pneumonia (CAP) is still an important and serious
      disease for elderly and geriatric patients. AIMS: For epidemiological and
      clinical reasons it is important to collate the frequencies of the various
      degrees of severity of CAP and to obtain information on the spread and degree of
      the threat to the various risk groups by CAP. In outpatient treatment a simple to
      execute prognosis score can be used to objectify the assessment of the clinical
      status of a patient and to support therapeutic decision-making. For this purpose
      knowledge of the appropriate instruments should be available to potential users.
      MATERIAL AND METHODS: Since the 1990s a variety of risk scores for stratification
      of CAP have been developed and evaluated. This article presents the content and
      value of the available risk scores whereby the advantages and disadvantages of
      the individual scores are critically compared. Special emphasis is placed on the
      importance of the risk scores for geriatric patients. RESULTS: At present the
      decision about outpatient or inpatient treatment is primarily based on the risk
      score CRB-65. Criteria for intensive care unit admissions are provided by the
      modified American Thoracic Society (ATS) set of criteria. Overall, risk scores
      are less reliable for elderly patients than for younger adults. CONCLUSION: For
      treatment decisions for the elderly, functional aspects should also be considered
      in addition to the aspects of risk scores discussed here. In particular, the
      decision about inpatient admission for elderly, geriatric CAP patients should be
      made on an individual basis taking the benefit-risk relationship into
      consideration.

PMID- 25957248
TI  - Discrimination in Health Care: Correlates of Health Care Discrimination Among
      Black Males.
AB  - Using data from the Indiana Black Men's Health Study ( N = 455), a community
      based sample of adult Black men, the primary aim of this study was to explore
      factors of health care discrimination, and to examine if such reports differed by
      age and the frequency of race thoughts. Approximately one in four men reported
      experiencing discrimination in the health care setting. Results from the
      multivariable logistic regression models suggested that frequent race thoughts
      (odds ratio [ OR]: 1.89, p < .05), not having health insurance ( OR: 1.80, p <
      .05), and increased depressive symptomology ( OR: 1.06, p < .01) were positively
      associated with reports of health care discrimination. A multiplicative
      interaction coefficient of age and frequency of race thoughts was included to
      determine if health care discrimination differed by age and frequency of race
      thoughts ( OR: 1.03, p = .08). Results from the predicted probability plot
      suggested that the likelihood of experiencing health care discrimination
      decreases with age ( OR: 0.97, p < .05). In particular, results suggested that
      between the ages of 33 and 53 years, Black men who experienced frequent race
      thoughts were more likely to report experiences of discrimination in the health
      care setting than men of the same age that did not experience frequent race
      thoughts. These results highlight the need for empirical work to better
      understand the experiences of Black men, a group less likely to utilize health
      care services than most adult groups within the health care setting.

PMID- 25957249
TI  - A Qualitative Study of African American/Black MSM's Experiences of Participating
      in a Substance Use and Sexual Risk Reduction Intervention.
AB  - The majority of new HIV infections in the United States are among men who have
      sex with men (MSM), and African American/Black MSM are especially affected.
      Employing a grounded theory approach, this study presents qualitative data from
      21 African American/Black MSM who participated in a substance use and sexual risk
      reduction intervention trial (Project ROOM [men Reaching Out to Other Men]) in
      South Florida. African American/Black MSM from Project ROOM reduced their
      substance use and sexual risk behaviors at a faster rate than other men in the
      study. The present study examines how the experiences of participation in Project
      ROOM influenced the behavior change among African American/Black MSM. In-depth
      interviews indicate that study assessments enhanced African American/Black men's
      mindfulness and self-realization of behaviors leading to behavior modification
      and changes in social relationships. Furthermore, these findings suggest that
      interventions tailored to the social environment of HIV transmission and
      substance use behaviors are key to reducing risk behaviors among this population.

PMID- 25957250
TI  - Diabetes Self-Management Behaviors, Medical Care, Glycemic Control, and Self
      Rated Health in U.S. Men by Race/Ethnicity.
AB  - Men, particularly minorities, have higher rates of diabetes as compared with
      their counterparts. Ongoing diabetes self-management education and support by
      specialists are essential components to prevent the risk of complications such as
      kidney disease, cardiovascular diseases, and neurological impairments. Diabetes
      self-management behaviors, in particular, as diet and physical activity, have
      been associated with glycemic control in the literature. Recommended medical care
      for diabetes may differ by race/ethnicity. This study examined data from the
      National Health and Nutrition Examination Surveys, 2007 to 2010 for men with
      diabetes (N = 646) from four racial/ethnic groups: Mexican Americans, other
      Hispanics, non-Hispanic Blacks, and non-Hispanic Whites. Men with adequate
      dietary fiber intake had higher odds of glycemic control (odds ratio = 4.31,
      confidence interval [1.82, 10.20]), independent of race/ethnicity. There were
      racial/ethnic differences in reporting seeing a diabetes specialist. Non-Hispanic
      Blacks had the highest odds of reporting ever seeing a diabetes specialist
      (84.9%) followed by White non-Hispanics (74.7%), whereas Hispanics reported the
      lowest proportions (55.2% Mexican Americans and 62.1% other Hispanics). Men
      seeing a diabetes specialist had the lowest odds of glycemic control (odds ratio
      = 0.54, confidence interval [0.30, 0.96]). The results of this study suggest that
      diabetes education counseling may be selectively given to patients who are not in
      glycemic control. These findings indicate the need for examining referral systems
      and quality of diabetes care. Future studies should assess the effectiveness of
      patient-centered medical care provided by a diabetes specialist with
      consideration of sociodemographics, in particular, race/ethnicity and gender.

PMID- 25957251
TI  - Dose-dependent expression of CLIP2 in post-Chernobyl papillary thyroid
      carcinomas.
AB  - A previous study on papillary thyroid carcinomas (PTC) in young patients who were
      exposed to (131)iodine from the Chernobyl fallout revealed an exclusive gain of
      chromosomal band 7q11.23 in exposed cases compared to an age-matched control
      cohort. CLIP2, a gene located within band 7q11.23 was shown to be differentially
      expressed between exposed and non-exposed cases at messenger RNA and protein
      level. Therefore, a standardized procedure for CLIP2 typing of PTCs has been
      developed in a follow-up study. Here we used CLIP2 typing data on 117 post
      Chernobyl PTCs from two cohorts of exposed patients with individual dose
      estimates and 24 non-exposed controls to investigate a possible quantitative dose
      response relationship of the CLIP2 marker. The 'Genrisk-T' cohort consisted of 45
      PTCs and the 'UkrAm' cohort of 72 PTCs. Both cohorts differed in mean dose (0.59
      Gy Genrisk-T, 1.2 Gy UkrAm) and mean age at exposure (AaE) (2 years Genrisk-T, 8
      years UkrAm), whilst the median latency (16 years Genrisk-T, 18 years UkrAm) was
      comparable. We analyzed the association between the binary CLIP2 typing and
      continuous thyroid dose with logistic regression. A clear positive dose-response
      relationship was found for young PTC cases [age at operation (AaO) < 20 years,
      AaE < 5 years]. In the elder age group a higher proportion of sporadic tumors is
      assumed due to a negligible dose response, suggesting different molecular
      mechanisms in sporadic and radiation-induced cases. This is further supported by
      the association of elder patients (AaO > 20 years) with positivity for BRAF V600E
      mutation.

PMID- 25957252
TI  - Identification of genes involved in the phosphate metabolism in Cryptococcus
      neoformans.
AB  - Cryptococcus neoformans is a pathogenic basidiomycetous yeast that can cause life
      threatening meningoencephalitis in immuno-compromized patients. To propagate in
      the human body, this organism has to acquire phosphate that functions in cellular
      signaling pathways and is also an essential component of nucleic acids and
      phospholipids. Thus it is reasonable to assume that C. neoformans (Cn) possesses
      a phosphate regulatory system (PHO system) analogous to that of other fungi. By
      BLAST searches using the amino acid sequences of the components of the PHO system
      of Saccharomyces cerevisiae (Sc), we found potential counterparts to ScPHO genes
      in C. neoformans, namely, acid phosphatase (CnPHO2), the cyclin-dependent protein
      kinase (CDK) inhibitor (CnPHO81), Pho85-cyclin (CnPHO80), and CDK (CnPHO85).
      Disruption of each candidate gene, except CnPHO85, followed by phenotypic
      analysis, identified most of the basic components of the CnPHO system. We found
      that CnPHO85 was essential for the growth of C. neoformans, having regulatory
      function in the CnPHO system. Genetic screening and ChIP analysis, showed that
      CnPHO4 encodes a transcription factor that binds to the CnPHO genes in a Pi
      dependent manner. By RNA-seq analysis of the wild-type and the regulatory mutants
      of the CnPHO system, we found C. neoformans genes whose expression is controlled
      by the regulators of the CnPHO system. Thus the CnPHO system shares many
      properties with the ScPHO system, but expression of those CnPHO genes that encode
      regulators is controlled by phosphate starvation, which is not the case in the
      ScPHO system (except ScPHO81). We also could identify some genes involved in the
      stress response of the pathogenic yeast, but CnPho4 appeared to be responsible
      only for phosphate starvation. 

PMID- 25957253
TI  - The stimulatory effect of the TLR4-mediated adjuvant glucopyranosyl lipid A is
      well preserved in old age.
AB  - Many subunit vaccines require adjuvants to improve their limited immunogenicity.
      Various adjuvant candidates targeting toll-like receptors (TLRs) are currently
      under development including the synthetic TLR4 agonist glucopyranosyl lipid A
      (GLA). GLA has been investigated in the context of influenza vaccine, which is of
      particular importance for the elderly population. This study investigates the
      effect of GLA on antigen-presenting cells from young (median age 29 years, range
      26-33 years) and older (median age 72 years, range 61-78 years) adults. Treatment
      with GLA efficiently increases the expression of co-stimulatory molecules on
      human monocyte-derived dendritic cells (DC) as well as on ex vivo myeloid DC.
      Expression of co-stimulatory molecules is less pronounced on ex vivo monocytes.
      Production of pro-inflammatory cytokines (IL-6, TNF-alpha, IL-12) as well as of
      the anti-inflammatory cytokine IL-10 is induced in monocyte-derived DC. In PBMC
      cultures myeloid DC and to an even greater extent monocytes produce TNF-alpha and
      IL-6 after stimulation with GLA. Production of IL-12 can also be observed in
      these cultures. There are no age-related differences in the capacity of GLA to
      induce expression of co-stimulatory molecules or production of cytokines by human
      antigen-presenting cells. Therefore, TLR4 agonists like GLA are particularly
      promising candidates as adjuvants of vaccines designed for elderly individuals. 

PMID- 25957254
TI  - Cartilage and chondrocyte response to extreme muscular loading and impact
      loading: Can in vivo pre-load decrease impact-induced cell death?
AB  - BACKGROUND: Impact loading causes cartilage damage and cell death. Pre-loading
      prior to impact loading may protect cartilage and chondrocytes. However, there is
      no systematic evidence and understanding of the effects of pre-load strategies on
      cartilage damage and chondrocyte death. This study aimed at determining the
      effects of the pre-load history on impact-induced chondrocyte death in an intact
      joint. METHODS: Patellofemoral joints from 42 rabbits were loaded by controlled
      quadriceps muscle contractions and an external impacter. Two extreme muscular
      loading conditions were used: (i) a short-duration, high intensity, static muscle
      contraction, and (ii) a long-duration, low-intensity, cyclic muscle loading
      protocol. A 5-Joule centrally-oriented, gravity-accelerated impact load was
      applied to the joints. Chondrocyte viability was quantified following the
      muscular loading protocols, following application of the isolated impact loads,
      and following application of the impact loads that were preceded by the muscular
      pre-loads. Joint contact pressures were measured for all loading conditions by a
      pressure-sensitive film. FINDINGS: Comparing to cartilage injured by impact
      loading alone, cartilage pre-loaded by static, maximal intensity, short-term
      muscle loads had lower cell death, while cartilage pre-loaded by repetitive, low
      intensity, long-term muscular loads has higher cell death. The locations of peak
      joint contact pressures were not strongly correlated with the locations of
      greatest cell death occurrence. INTERPRETATION: Static, high intensity, short
      muscular pre-load protected cells from impact injury, whereas repetitive, low
      intensity, prolonged muscular pre-loading to the point of muscular fatigue left
      the chondrocytes vulnerable to injury. However, cell death seems to be unrelated
      to the peak joint pressures.

PMID- 25957255
TI  - Insights into the amplification of bacterial resistance to erythromycin in
      activated sludge.
AB  - Wastewater treatment plants are significant reservoirs for antimicrobial
      resistance. However, little is known about wastewater treatment effects on the
      variation of antibiotic resistance. The shifts of bacterial resistance to
      erythromycin, a macrolide widely used in human medicine, on a lab-scale activated
      sludge system fed with real wastewater was investigated from levels of bacteria,
      community and genes, in this study. The resistance variation of total
      heterotrophic bacteria was studied during the biological treatment process, based
      on culture dependent method. The alterations of bacterial community resistant to
      erythromycin and nine typical erythromycin resistance genes were explored with
      molecular approaches, including high-throughput sequencing and quantitative
      polymerase chain reaction. The results revealed that the total heterotrophs
      tolerance level to erythromycin concentrations (higher than 32 mg/L) was
      significantly amplified during the activated sludge treatment, with the
      prevalence increased from 9.6% to 21.8%. High-throughput sequencing results
      demonstrated an obvious increase of the total heterotrophic bacterial diversity
      resistant to erythromycin. Proteobacteria and Bacteroidetes were the two dominant
      phyla in the influent and effluent of the bioreactor. However, the prevalence of
      Proteobacteria decreased from 76% to 59% while the total phyla number increased
      greatly from 18 to 29 through activated sludge treatment. The gene proportions of
      erm(A), mef(E) and erm(D) were greatly amplified after biological treatment. It
      is proposed that the transfer of antibiotic resistance genes through the variable
      mixtures of bacteria in the activated sludge might be the reason for the
      antibiotic resistance amplification. The amplified risk of antibiotic resistance
      in wastewater treatment needs to be paid more attention.

PMID- 25957256
TI  - Inverted verrucous carcinoma of the buttock mimicking abscess and gossypiboma: MR
      and pathologic correlation.
AB  - Verrucous carcinoma (VC) is an uncommon, low-grade variant of squamous cell
      carcinoma. Its benign histologic appearance and indolent course may lead to a
      delayed diagnosis. We report a rare case of an inverted verrucous carcinoma of
      the buttock presenting as a slow-growing subcutaneous lesion with a draining
      sinus and no exophytic component, clinically mimicking abscess and gossypiboma,
      with magnetic resonance imaging (MRI) and pathologic correlation. Biopsy of the
      lesional base is mandatory for accurate diagnosis. An enhancement pattern with a
      convoluted undulating appearance in a subcutaneous lesion displayed on MRI should
      raise a consideration of inverted VC in the differential diagnosis. 

PMID- 25957257
TI  - Small-Fiber Neuropathy: A Diabetic Microvascular Complication of Special
      Clinical, Diagnostic, and Prognostic Importance.
AB  - Damage of small nerve fibers may lead to a large variety of clinical symptoms.
      Small-fiber neuropathy underlies the symptoms of painful diabetic neuropathy,
      which may decrease quality of life. It also contributes to the poor prognosis of
      diabetic neuropathy because it plays a key role in the pathogenesis of foot
      ulceration and autonomic neuropathy. Impairment of small nerve fibers is
      considered the earliest alteration in the course of diabetic neuropathy.
      Therefore, assessment of functional and morphological abnormalities of small
      nerve fibers may enable timely diagnosis. The definition, symptoms, and clinical
      significance of small-fiber neuropathy are considered in the present review. An
      apparently more complex interaction between small-fiber impairment and
      microcirculation is extensively discussed. Diagnostic modalities include
      morphometric and functional methods. Corneal confocal microscopy and punch skin
      biopsy are considered gold standards, but noninvasive functional tests are also
      diagnostically useful. However, in routine clinical practice, small-fiber
      neuropathy is diagnosed by its typical clinical presentation. Finally, prompt
      treatment should be initiated following diagnosis. 

PMID- 25957258
TI  - Uric Acid and Peripheral Arterial Disease.

PMID- 25957259
TI  - The Relation Between Neutrophil-Lymphocyte Ratio and Endothelial Dysfunction.

PMID- 25957260
TI  - Studies on the molecular docking and amino Acid residues involving in recognition
      of substrate in proline iminopeptidase by site-directed mutagenesis.
AB  - The proline iminopeptidase (PchPiPA) of Phanerochaete chrysosporium catalyze
      specifically hydrolysis of N-terminal proline from peptides. The substrate Pro
      pNA was docked into the catalytic pocket and several amino acid residues were
      identified to interact or associate with the substrate. Eight residues were
      selected for site-directed mutagenesis. The wild-type and mutant proteins were
      expressed in Escherichia coli and purified. Kinetic parameters were calculated by
      hydrolyzing Pro-pNA for these enzymes. Substitution of two Glu residues (Glu198
      and Glu227) which interact with the substrate via formation of hydrogen bond, led
      to deleterious effect on catalytic efficiency (k(cat)/K(m)) due to decrease of
      k(cat) and increase of K(m). Four Phe residues consisting of catalytic pocket and
      surrounding the docked substrate, were substituted with Ala, resulting in
      decrease in k(cat)/K(m) to various extents. Substitution of two residues (Val267
      and Cys267) localized at the deep end of the catalytic pocket also yielded
      negative influence on the substrate hydrolysis. Besides, all the mutants except
      E227Q exhibited lower thermostability than the wild-type did, indicating that
      these mutations may modulate the local structure. In conclusion, these amino acid
      residues may play an important role in maintaining local environment of the
      impacted catalytic pocket and be involved in recognizing or positioning the
      substrate.

PMID- 25957261
TI  - Finite element implementation of a multiscale model of the human lens capsule.
AB  - An axisymmetric finite element implementation of a previously described
      structural constitutive model for the human lens capsule (Burd in Biomech Model
      Mechanobiol 8(3):217-231, 2009) is presented. This constitutive model is based on
      a hyperelastic approach in which the network of collagen IV within the capsule is
      represented by an irregular hexagonal planar network of hyperelastic bars,
      embedded in a hyperelastic matrix. The paper gives a detailed specification of
      the model and the periodic boundary conditions adopted for the network component.
      Momentum balance equations for the network are derived in variational form. These
      balance equations are used to develop a nonlinear solution scheme to enable the
      equilibrium configuration of the network to be computed. The constitutive model
      is implemented within a macroscopic finite element framework to give a multiscale
      model of the lens capsule. The possibility of capsule wrinkling is included in
      the formulation. To achieve this implementation, values of the first and second
      derivatives of the strain energy density with respect to the in-plane stretch
      ratios need to be computed at the local, constitutive model, level. Procedures to
      determine these strain energy derivatives at equilibrium configurations of the
      network are described. The multiscale model is calibrated against previously
      published experimental data on isolated inflation and uniaxial stretching of ex
      vivo human capsule samples. Two independent example lens capsule inflation
      analyses are presented. 

PMID- 25957262
TI  - Ethical challenges in orthopedic surgery.
AB  - Despite our recent attention to ethical issues in orthopedics, we are still faced
      with multiple conflicts of interest that continue to pose ethical dilemmas to the
      practicing physician. Using four case scenarios, we review the potential
      conflicts of interest and the dilemmas posed by these frequently encountered
      situations. The ethical conflicts confronted in resident training, the
      introduction of new technology, physician advertising, and the obligations of the
      sports team physician are reviewed and discussed. The basic principles of medical
      ethics, including acting for the good of the patients and doing no harm, are
      discussed in the context of the four case scenarios. 

PMID- 25957263
TI  - Resistance to receptor tyrosine kinase inhibition in cancer: molecular mechanisms
      and therapeutic strategies.
AB  - Drug resistance is a major factor that limits the efficacy of targeted cancer
      therapies. In this review, we discuss the main known mechanisms of resistance to
      receptor tyrosine kinase inhibitors, which are the most prevalent class of
      targeted therapeutic agent in current clinical use. Here we focus on bypass track
      resistance, which involves the activation of alternate signaling molecules by
      tumor cells to bypass inhibition and maintain signaling output, and consider the
      problems of signaling pathway redundancy and how the activation of different
      receptor tyrosine kinases translates into intracellular signal transduction in
      different cancer types. This information is presented in the context of research
      strategies for the discovery of new targets for pharmacological intervention,
      with the goal of overcoming resistance in order to improve patient outcomes. 

PMID- 25957264
TI  - Regulatory B cells in human inflammatory and autoimmune diseases: from mouse
      models to clinical research.
AB  - B cells have been generally considered to be positive regulators of immune
      responses because of their ability to produce antigen-specific antibodies and to
      activate T cells through antigen presentation. Impairment of B cell development
      and function may cause inflammatory and autoimmune diseases. Recently, specific B
      cell subsets that can negatively regulate immune responses have been described in
      mouse models of a wide variety of inflammatory and autoimmune diseases. The
      concept of those B cells, termed regulatory B cells, is now recognized as
      important in the murine immune system. Among several regulatory B cell subsets,
      IL-10-producing regulatory B cells are the most widely investigated. On the basis
      of discoveries from studies of such mice, human regulatory B cells that produce
      IL-10 in most cases are becoming an active area of research. There have been
      emerging data suggesting the importance of human regulatory B cells in various
      diseases. Revealing the immune regulation mechanisms of human regulatory B cells
      in human inflammatory and autoimmune diseases could lead to the development of
      novel B cell targeted therapies. This review highlights the current knowledge on
      regulatory B cells, mainly IL-10-producing regulatory B cells, in animal models
      of inflammatory and autoimmune diseases and in clinical research using human
      samples. 

PMID- 25957265
TI  - Signals controlling the development and activity of regulatory B-lineage cells.
AB  - The fundamental concepts surrounding B cells with inhibitory function (regulatory
      B cells) are now being established. In the context of autoimmune and inflammatory
      animal models, B cells play an immunomodulatory role via IL-10 production and
      contribute to limitation of the pathogenesis. Recent studies have notably
      identified the human counterparts of these cells, which have been suggested to be
      relevant to the pathophysiology of disease. Clear criteria to identify these cell
      subsets and the key molecular mechanisms underlying their physiological features
      are required for understanding the big picture of regulatory B cells.
      Plasmablasts have recently been identified as a major IL-10-producing regulatory
      B-cell subset and Ca(2+) signaling has furthermore been found to contribute to B
      cell IL-10 expression. In this review, the signaling components controlling IL-10
      dependent B-cell regulatory function and the development of IL-10-competent/
      producing B cells and plasmablasts are discussed. 

PMID- 25957266
TI  - Innate response activator B cells: origins and functions.
AB  - Innate response activator (IRA) B cells are a subset of B-1a derived B cells that
      produce the growth factors granulocyte macrophage colony stimulating factor and
      IL-3. In mouse models of sepsis and pneumonia, B-1a B cells residing in serosal
      sites recognize bacteria, migrate to the spleen or lung, and differentiate to IRA
      B cells that then contribute to the host response by amplifying inflammation and
      producing polyreactive IgM. In atherosclerosis, IRA B cells accumulate in the
      spleen, where they promote extramedullary hematopoiesis and activate classical
      dendritic cells. In this review, we focus on the ontogeny and function of IRA B
      cells in acute and chronic inflammation. 

PMID- 25957267
TI  - The cell surface receptor Slamf6 modulates innate immune responses during
      Citrobacter rodentium-induced colitis.
AB  - The homophilic cell surface receptors CD150 (Slamf1) and CD352 (Slamf6) are known
      to modulate adaptive immune responses. Although the Th17 response was enhanced in
      Slamf6(-/-) C57BL/6 mice upon oral infection with Citrobacter rodentium, the
      pathologic consequences are indistinguishable from an infection of wild-type
      C57BL/6 mice. Using a reporter-based binding assay, we show that Slamf6 can
      engage structures on the outer cell membrane of several Gram(-) bacteria.
      Therefore, we examined whether Slamf6, like Slamf1, is also involved in innate
      responses to bacteria and regulates peripheral inflammation by assessing the
      outcome of C. rodentium infections in Rag(-/-) mice. Surprisingly, the pathology
      and immune responses in the lamina propria of C. rodentium-infected Slamf6(-/-)
      Rag(-/-) mice were markedly reduced as compared with those of Rag(-/-) mice.
      Infiltration of inflammatory phagocytes into the lamina propria was consistently
      lower in Slamf6(-/-) Rag(-/-) mice than in Rag(-/-) animals. Concomitant with the
      reduced systemic translocation of the bacteria was an enhanced production of IL
      22, suggesting that Slamf6 suppresses a mucosal protective program. Furthermore,
      administering a mAb (330) that inhibits bacterial interactions with Slamf6 to
      Rag(-/-) mice ameliorated the infection compared with a control antibody. We
      conclude that Slamf6-mediated interactions of colonic innate immune cells with
      specific Gram(-) bacteria reduce mucosal protection and enhance inflammation,
      contributing to lethal colitis that is caused by C. rodentium infections in Rag(
      /-) mice.

PMID- 25957268
TI  - Inflammatory response of endothelial cells to a human endogenous retrovirus
      associated with multiple sclerosis is mediated by TLR4.
AB  - The MSRV (multiple sclerosis-associated retrovirus) belongs to the human
      endogenous retrovirus HERV-W family. The envelope protein originating from the
      MSRV has been found in most patients with multiple sclerosis (MS). This protein
      (Env-ms) has pro-inflammatory properties for several types of immune cells and
      could therefore play a role in MS pathogenesis by promoting the leukocyte
      diapedesis observed in the central nervous system of patients. Our study aims to
      analyze the effects of Env-ms on the blood-brain barrier (BBB) at a molecular and
      functional level. We demonstrate that the recombinant MSRV envelope is able to
      stimulate several inflammatory parameters in a human BBB in vitro model, the
      HCMEC/D3 brain endothelial cell line. Indeed, Env-ms induces over-expression of
      ICAM-1, a major mediator of leukocyte adhesion to endothelial cells, in a dose
      dependent manner as well as a strong dose-dependent production of the pro
      inflammatory cytokines IL-6 and IL-8. Furthermore, using a silencing approach
      with siRNAs, we show that Env-ms is recognized via the Toll-like receptor 4
      receptor, a pattern recognition receptor of innate immunity present on
      endothelial cells. We also show, using functional assays, that treatment of brain
      endothelial cells with Env-ms significantly stimulated the adhesion and the
      transmigration of activated immune cells through a monolayer of endothelial
      cells. These findings support the hypothesis that MSRV could be involved in the
      pathogenesis of MS disease or at least in maintenance of inflammatory conditions,
      thus fueling the auto-immune disorder. MSRV could also play a role in other
      chronic inflammatory diseases. 

PMID- 25957269
TI  - A Community Study on the Relationship of Posttraumatic Cognitions to
      Internalizing and Externalizing Psychopathology in Taiwanese Children and
      Adolescents.
AB  - A growing number of studies indicate that posttraumatic cognitions play a crucial
      role in the development and maintenance of posttraumatic stress disorder (PTSD).
      However, the effects of posttraumatic cognitions on general psychopathology
      beyond PTSD remain unclear. The current study aimed to validate the Chinese
      version of the Child Posttraumatic Cognitions Inventory (CPTCI-C) and to
      investigate the relationship between posttraumatic cognitions and
      psychopathology. A community sample of 285 school-aged children and adolescents
      (aged 9-17, 160 [56.1 %] female) reported their trauma-related cognitions on the
      CPTCI-C and completed measures of symptoms of PTSD, depression, and generalized
      anxiety. Parents reported their children's internalizing and externalizing
      problems. We validated a revised version of the CPTCI-C based on the results of
      confirmatory factor analyses. The resulting evidence suggests that this revised
      CPTCI-C possesses good internal consistency, fair 6-week temporal stability, and
      good concurrent validity. In addition to significant correlations between
      posttraumatic cognitions and internalizing and externalizing psychopathology,
      after controlling for age, gender, and trauma types, both the revised CPTCI-C
      subscale scores conveyed unique contributions to psychological distress while
      only the maladaptive appraisals of the trauma remained weakly associated with
      externalizing problems. Structural equation modeling analysis showed that
      maladaptive appraisals of the trauma had a direct longitudinal impact on chronic
      PTSD severity. No mediation effect of posttraumatic cognitions on the
      relationship between acute and chronic PTSD activity was observed. The
      implications of our findings are discussed for the specificity of posttraumatic
      cognitions to posttraumatic internalizing psychopathology and cognitive
      interventions that target negative trauma-related cognitions.

PMID- 25957271
TI  - Influence of Light Intensity on Growth and Pigment Production by Monascus ruber
      in Submerged Fermentation.
AB  - To reduce environmental problems caused by glycerine accumulation and to make the
      production of biodiesel more profitable, crude glycerin without treatment was
      used as substrate for obtaining higher value-added bioproducts. Monascus ruber is
      a filamentous fungus that produces pigments, particularly red ones, which are
      used for coloring foods (rice wine and meat products). The interest in developing
      pigments from natural sources is increasing due to the restriction of using
      synthetic dyes. The effects of temperature, pH, microorganism morphology,
      aeration, nitrogen source, and substrates have been studied in the cultivation of
      M. ruber. In this work, it was observed that light intensity is also an important
      factor that should be considered for understanding the metabolism of the fungus.
      In M. ruber cultivation, inhibition of growth and pigment production was observed
      in Petri dishes and blaffed flasks exposed to direct illumination. Growth and
      pigment production were higher in Petri dishes and flasks exposed to red light
      and in the absence of light. Radial growth rate of M. ruber in plates in darkness
      was 1.50 mm day(-1) and in plates exposed to direct illumination was 0.59 mm day(
      1). Maximum production of red pigments (8.32 UA) and biomass (8.82 g L(-1)) were
      obtained in baffled flasks covered with red film and 7.17 UA of red pigments, and
      7.40 g L(-1) of biomass was obtained in flasks incubated in darkness. Under
      conditions of 1248 lux of luminance, the maximum pigment production was 4.48 UA,
      with production of 6.94 g L(-1) of biomass, indicating that the fungus has
      photoreceptors which influence the physiological responses.

PMID- 25957272
TI  - Characteristics and Applicability of Phytase of the Yeast Pichia anomala in
      Synthesizing Haloperoxidase.
AB  - The phytase of the yeast Pichia anomala is a histidine acid phosphatase based on
      signature sequences and catalytic amino acids identified by site-directed
      mutagenesis. Among modulators, N-bromosuccinimide and butanedione inhibit
      phytase, while Ca(2+) and Ni(2+) stimulate slightly. Vanadate exhibits
      competitive inhibition of phytase, making it bifunctional to act as
      haloperoxidase. Molecular docking supports vanadate to share its binding site
      with phytate. The T 1/2, activation energy (E a ), temperature quotient (Q 10),
      activation energy of thermal inactivation (Ed), and enthalpy (DeltaH d (0) ) of
      the enzyme are 4.0 min (80  degrees C), 27.72 kJ mol(-1), 2.1, 410.62 kJ mol(-1),
      and ~407.8 kJ mol(-1) (65-80  degrees C), respectively. The free energy of the
      process (DeltaG d (o) ) increases from 49.56 to 71.58 kJ mol(-1) with rise in
      temperature, while entropy of inactivation (DeltaS d (0) ) remains constant at
      ~1.36 kJ mol(-1) K(-1). The supplementation of whole wheat dough with rPPHY
      resulted in 72.5 % reduction in phytic acid content of bread. These
      characteristics confirm that the phytase has adequate thermostability for its
      applicability as a food and feed additive.

PMID- 25957273
TI  - Comparison of Aerobic and Anaerobic Biodegradation of Sugarcane Vinasse.
AB  - Vinasse is the main liquid waste from ethanol production, and it has a
      considerable pollution potential. Biological treatment is a promising alternative
      to reduce its organic load. The aim of this study was to analyze the
      biodegradation of sugarcane juice vinasse in aerobic and anaerobic conditions.
      The content of carbohydrates, proteins and volatile fatty acids was evaluated.
      Vinasse samples showed a high biodegradability (>96.5 %) and low percentage of
      inert chemical oxygen demand (COD) (<3.2 %) in both aerobic and anaerobic
      conditions. The rates of substrate utilization were slightly higher in aerobic
      reactors, but COD stabilization occurred simultaneously in the anaerobic
      reactors, confirming its suitability for anaerobic digestion. Inert COD in
      anaerobic conditions was lower than in aerobic conditions. On the other hand, COD
      from metabolic products in the anaerobic reactors was higher than in the aerobic
      ones, indicating an increased release of soluble microbial products (SMPs) by
      anaerobic microorganisms. The results indicated that carbohydrates were
      satisfactorily degraded and protein-like substances were the major components
      remaining after biological degradation of vinasse.

PMID- 25957270
TI  - Organization of chlorophyll biosynthesis and insertion of chlorophyll into the
      chlorophyll-binding proteins in chloroplasts.
AB  - Oxygenic photosynthesis requires chlorophyll (Chl) for the absorption of light
      energy, and charge separation in the reaction center of photosystem I and II, to
      feed electrons into the photosynthetic electron transfer chain. Chl is bound to
      different Chl-binding proteins assembled in the core complexes of the two
      photosystems and their peripheral light-harvesting antenna complexes. The
      structure of the photosynthetic protein complexes has been elucidated, but
      mechanisms of their biogenesis are in most instances unknown. These processes
      involve not only the assembly of interacting proteins, but also the functional
      integration of pigments and other cofactors. As a precondition for the
      association of Chl with the Chl-binding proteins in both photosystems, the
      synthesis of the apoproteins is synchronized with Chl biosynthesis. This review
      aims to summarize the present knowledge on the posttranslational organization of
      Chl biosynthesis and current attempts to envision the proceedings of the
      successive synthesis and integration of Chl into Chl-binding proteins in the
      thylakoid membrane. Potential auxiliary factors, contributing to the control and
      organization of Chl biosynthesis and the association of Chl with the Chl-binding
      proteins during their integration into photosynthetic complexes, are discussed in
      this review. 

PMID- 25957274
TI  - Markerless Deletion System for Escherichia coli Using Short Homologous Sequences
      and Positive-Negative Selectable Cassette.
AB  - Red homologous recombination has been extensively used in recombineering. Because
      foreign sequences, such as antibiotic resistance genes, FRT-sites, or loxP-sites,
      are often unwanted in mutant Escherichia coli, we established a markerless
      deletion system containing short homologous sequences, a positive-selectable
      marker (kan), and a negative-selectable marker (sacB) for E. coli. For markerless
      deletion of a specific region of the E. coli genome, a two-step recombination
      procedure using two different PCR fragments, which were amplified from pUC57-kan
      sacB and pUC57-298, was performed. The generation of a pheA-tyrA deficient mutant
      demonstrated that this markerless deletion system was a simple and efficient
      method to generate markerless chromosomal deletions in E. coli.

PMID- 25957275
TI  - Expression and Characterization of a Novel Thermo-Alkalistable Lipase from
      Hyperthermophilic Bacterium Thermotoga maritima.
AB  - A gene coding for lipase (Tm1350) from the hyperthermophilic bacterium Thermotoga
      maritima MSB8 was cloned and overexpressed by Escherichia coli. The enzyme can
      degrade substrates with both short and long acyl chain lengths. The apparent Km
      and Vmax values for p-nitrophenyl butyrate were 8 mM and 333 U/mg, respectively.
      The enzyme displayed optimal activity at pH 7.5 and 70  degrees C, maintained 66
      % of the original activity after 8 h of incubation, and its half-lives at pHs 9
      and 10 were 8 and 1 h. The activity of Tm1350 was stimulated up to 131 or 151 %
      of the original activity by incubating with 4 M urea or 20 % (v/v) methanol, and
      90.1 or 70.2 % of the activity was maintained after 8 h incubation of the enzyme
      in 20 or 75 % (v/v) of the methanol, showing potential for biodiesel production.
      The activity of the enzyme without cysteine residue was stimulated up to 618 and
      550 % of the original activity by incubating with dithiothreitol (DTT) and
      reduced glutathione (GSH) at a concentration of 1 mM. However, the circular
      dichroism spectra of the enzyme have no obvious change after DTT treatment. It is
      speculated that DTT interacts with potential residues in some key active sites
      without influence of structure.

PMID- 25957276
TI  - A Genome-Wide Survey of Date Palm Cultivars Supports Two Major Subpopulations in
      Phoenix dactylifera.
AB  - The date palm (Phoenix dactylifera L.) is one of the oldest cultivated trees and
      is intimately tied to the history of human civilization. There are hundreds of
      commercial cultivars with distinct fruit shapes, colors, and sizes growing mainly
      in arid lands from the west of North Africa to India. The origin of date palm
      domestication is still uncertain, and few studies have attempted to document
      genetic diversity across multiple regions. We conducted genotyping-by-sequencing
      on 70 female cultivar samples from across the date palm-growing regions,
      including four Phoenix species as the outgroup. Here, for the first time, we
      generate genome-wide genotyping data for 13,000-65,000 SNPs in a diverse set of
      date palm fruit and leaf samples. Our analysis provides the first genome-wide
      evidence confirming recent findings that the date palm cultivars segregate into
      two main regions of shared genetic background from North Africa and the Arabian
      Gulf. We identify genomic regions with high densities of geographically
      segregating SNPs and also observe higher levels of allele fixation on the
      recently described X-chromosome than on the autosomes. Our results fit a model
      with two centers of earliest cultivation including date palms autochthonous to
      North Africa. These results adjust our understanding of human agriculture history
      and will provide the foundation for more directed functional studies and a better
      understanding of genetic diversity in date palm. 

PMID- 25957277
TI  - Intrinsic Toxicity of Unchecked Heterochromatin Spread Is Suppressed by Redundant
      Chromatin Boundary Functions in Schizosacchromyces pombe.
AB  - Effective boundary mechanisms halt the spread of repressive histone methylation.
      In the fission yeast Schizosacchromyces pombe, two factors/elements required for
      boundary function have been described, the jmjC protein Epe1 and binding sites
      for the RNA polymerase III transcription factor TFIIIC. Perplexingly, individual
      mutation of Epe1 or TFIIIC sites produces only mild boundary defects, and no
      other boundary factors have been identified. To approach these issues, we
      developed a synthetic reporter gene tool that uses a tethered Clr4 histone H3K9
      methyltransferase and monitors the ability of a DNA element to block
      heterochromatin spread. The inverted repeat (IR) that flanks the mat2/3 silent
      mating-type cassette region demonstrates strong boundary activity compared to
      sequences that flank pericentromeric heterochromatic repeats. Rather than acting
      in the same inhibitory pathway, Epe1 and TFIIIC sites mediate boundary function
      of the IR via the two parallel and largely redundant pathways. We also use the
      system to demonstrate that HP1/Swi6 promotes boundary activity in addition to
      promoting silencing and acts in the same pathway as Epe1. Inhibition of
      heterochromatin spread at the endogenous IR element also requires either Epe1 or
      TFIIIC sites. Strikingly, mutation of both mechanisms results in growth
      inhibition that is associated with the spread of heterochromatin over many
      kilobases to the nearest essential gene and the near-complete silencing of
      several intervening euchromatic genes. The growth defect is reversed by deletion
      of clr4+, indicating that the redundant boundary mechanisms protect cells from
      intrinsic toxicity caused by the spread of heterochromatin. 

PMID- 25957278
TI  - Age-related differences in the P3 amplitude in change blindness.
AB  - Observers often miss visual changes in the environment when they co-occur with
      other visual disruptions. This phenomenon is called change blindness. Previous
      research has shown that change blindness increases with age. The aim of the
      current study was to explore the role of post-perceptual stimulus processing in
      age differences. Therefore, the P3 component of the event-related potential was
      measured while younger, middle-aged, and older participants performed a change
      detection task under different task demands. Older adults detected fewer changes
      than younger adults, even when the task was very easy. Detected changes elicited
      greater P3 amplitudes than undetected changes in younger adults. This effect was
      reduced or even absent for middle-aged and older participants, irrespective of
      task demands. Because this P3 effect is supposed to reflect participants'
      confidence in change detection, less confidence in own responses may explain the
      decline of change detection performance in normal aging. 

PMID- 25957280
TI  - The RAMC at Belsen 1945: typhus revisited.
AB  - OBJECTIVE: The Royal Army Medical Corps (RAMC) has justly regarded its relief of
      the appalling conditions found in the liberated Nazi concentration camp at Bergen
      Belsen in April 1945 as one of its more glorious achievements. This view has, in
      the last decade, come under attack from historians who have, inter alia,
      criticised the nature and speed of the medical measures employed by the British.
      This has focused particularly on the management of the typhus epidemic,
      erroneously claimed to be the major disease killer of the survivors, and which
      was the catalyst for the premature German surrender of the camp to the
      approaching Allies about 3 weeks before the end of the war. This review examines
      the veracity of this statement and the nature of the evidence on which it was
      based. METHODS: Review of all the relevant extant primary source written evidence
      both published and archived in major collections in London, Washington and
      Belsen, in addition to the relevant subsequent secondary evidence. RESULTS:
      Disprove the ill-considered and scientifically flawed attempts to discredit the
      RAMC and demonstrate that the RAMC can be shown to have made the correct
      prioritising decisions in relieving starvation as well as in implementing the
      appropriate public health anti-typhus measures and to have acquitted itself
      honourably. DISCUSSION: Underlines the pitfalls of basing sweeping conclusions on
      an imperfectly understood inadequate selection of the available evidence.

PMID- 25957279
TI  - Does the anticipation of compatible partner reactions facilitate action planning
      in joint tasks?
AB  - Observing another human's actions influences action planning, but what about
      merely anticipating them? In joint action settings where a partner's subsequent
      actions are a consequence of one's own actions, such contingent partner reactions
      can be regarded as action effects. Therefore, just like automatic effects they
      might facilitate those of a person's actions that overlap with them in relevant
      features. In Experiments 1 and 2, the spatial compatibility of contingent partner
      reactions was manipulated and compared with the influence of automatic effects.
      Experiment 1 used a simplistic scenario in which lateral keypress actions by the
      subject were responded to by mouse movements of a partner producing spatially
      compatible or incompatible visual effects. Experiment 2 transferred the paradigm
      to a more complex task in which subjects manually relocated virtual objects on a
      multi-touch display, and these or other objects were subsequently manipulated by
      the partner. In Experiment 1, compatible partner reactions speeded up subjects'
      preceding actions, whereas in Experiment 2 the influence was not statistically
      reliable. To test whether influences of partner reaction compatibility could be
      found in such naturalistic settings at all, Experiment 3 also used a multi-touch
      setting but varied temporal instead of spatial compatibility, which has several
      methodological advantages. This time, a compatibility effect emerged in subjects'
      movement initiation times, whereas contrast effects were found for movement
      durations. These findings indicate that the principles of ideomotor action
      control can be extended to joint action settings. At the same time, they also
      emphasize the importance of task features in determining whether our own
      behaviour is influenced by anticipations of another person's reactions. 

PMID- 25957281
TI  - Calcium negatively regulates meprin beta activity and attenuates substrate
      cleavage.
AB  - The meprin beta metalloproteinase is an important enzyme in extracellular matrix
      turnover, inflammation, and neurodegeneration in humans and mice. Previous
      studies showed a diminished cleavage of certain meprin beta substrates in the
      presence of calcium, although the mechanism was not clear. With the help of a
      specific fluorogenic peptide assay and the human amyloid precursor protein as
      substrate, we demonstrated that the influence of calcium is most likely a direct
      effect on human meprin beta itself. Analyzing the crystal structures of pro- and
      mature meprin beta helped to identify a cluster of negatively charged amino acids
      forming a potential calcium binding site. Mutation of 2 of these residues (D204A
      and D245A) led to severe differences in proteolytic activity and cellular
      localization of meprin beta. D245A was almost completely inactive and largely
      stored into intracellular vesicles, indicating severe misfolding of the protein.
      Astonishingly, D204A was not transported to the cell surface, but exhibited
      strong beta-secretase activity, resulting in massive accumulation of Abeta
      peptides. This could be explained by constitutive maturation of this meprin beta
      mutant already in the early secretory pathway. We hypothesize that lacking D204
      abrogates the capability of binding calcium in the catalytic domain, an important
      step for proper folding of the propeptide and subsequent inhibition of the
      protease. This is supported by the inhibition constant of calcium for meprin beta
      (inhibitory constant 50 = 11 mM), which resembles the physiologic concentrations
      found in the endoplasmic reticulum. For instance, it was shown for amyotrophic
      lateral sclerosis that a loss of calcium in the endoplasmic reticulum leads to
      the misfolding of calcium-dependent proteins, which might also be relevant for
      proper function of meprin beta.

PMID- 25957282
TI  - Activation of autophagy in human skeletal muscle is dependent on exercise
      intensity and AMPK activation.
AB  - In humans, nutrient deprivation and extreme endurance exercise both activate
      autophagy. We hypothesized that cumulating fasting and cycling exercise would
      potentiate activation of autophagy in skeletal muscle. Well-trained athletes were
      divided into control (n = 8), low-intensity (LI, n = 8), and high-intensity (HI,
      n = 7) exercise groups and submitted to fed and fasting sessions. Muscle biopsy
      samples were obtained from the vastus lateralis before, at the end, and 1 h after
      a 2 h LI or HI bout of exercise. Phosphorylation of ULK1(Ser317) was higher after
      exercise (P < 0.001). In both the fed and the fasted states, LC3bII protein level
      and LC3bII/I were decreased after LI and HI (P < 0.05), while p62/SQSTM1 was
      decreased only 1 h after HI (P < 0.05), indicating an increased autophagic flux
      after HI. The autophagic transcriptional program was also activated, as evidenced
      by the increased level of LC3b, p62/SQSTM1, GabarapL1, and Cathepsin L mRNAs
      observed after HI but not after LI. The increased autophagic flux after HI
      exercise could be due to increased AMP-activated protein kinase alpha (AMPKalpha)
      activity, as both AMPKalpha(Thr172) and ACC(Ser79) had a higher phosphorylation
      state after HI (P < 0.001). In summary, the most effective strategy to activate
      autophagy in human skeletal muscle seems to rely on exercise intensity more than
      diet.

PMID- 25957283
TI  - Epidemiology of traumatic spinal cord injuries in Austria 2002-2012.
AB  - PURPOSE: The aim of this study was to analyse the epidemiological patterns
      (mortality, incidence of non-fatal cases and overall incidence), of traumatic
      spinal cord injuries (TSCI) in 2002-2012 in Austria. METHODS: TSCI-related deaths
      and hospital admissions in Austria 2002-2012 were obtained from Statistics
      Austria and analysed. Mortality rates, as well as non-fatal and overall incidence
      rates were calculated and compared across the age spectrum and by sex.
      Additionally, the main causes and demographic characteristics of victims were
      analysed. RESULTS: The crude overall incidence rate of TSCI was 16.96, CI 95 %
      16.95-16.97 and the standardized incidence rate was 13.98, CI 95 % 13.97-13.99
      per million (annual average rate). An annual increase in fatality rates was
      observed occurring mostly in the age group >65 years (Kendall's Tau = 0.1). Falls
      (mortality rate 19.58, CI 95 % 19.57-19.59) and injuries at home (incidence rate
      56.57, CI 95 % 56.56-56.58) were the principal causes of fatal and non-fatal
      TSCI, respectively. Injuries to the neck region were the most common. All
      indicators were the highest for the age group >65 years: non-fatal incidence rate
      23.55, CI 95 % 23.54-23.56; mortality rate 21.4, CI 95 % 21.39-21.41; and overall
      incidence rate 47.9, CI 95 % 47.89-47.91. A clear male dominance was observed
      (incidence rate ratio 1.9, CI 95 % 1.4-2.7). CONCLUSION: The population >65 years
      has been at the highest risk of TSCI in Austria for the analysed period and
      therefore preventive activities should be focused on this group. The increasing
      overall incidence of TSCI was driven by the increasing mortality rates that were
      highest in the age group >65 years. We advocate harmonization of epidemiological
      reporting especially regarding aetiology of TSCI in order to better inform policy
      makers and prevention.

PMID- 25957284
TI  - Analysis of the relationship between coronal and sagittal deformities in
      adolescent idiopathic scoliosis.
AB  - PURPOSE: To characterize the sagittal alignment of each Lenke type and
      investigate the relationship between coronal and sagittal deformities in
      adolescent idiopathic scoliotic (AIS) patients. METHODS: A cohort of 184 subjects
      with AIS was retrospectively recruited. Radiographic data were measured and
      collected, including the Lenke types, Cobb angles of structural curves, and
      sagittal spino-pelvic parameters. Subjects were grouped according to their
      genders, Lenke curve types, lumbar modifiers and the amount of coronal structural
      curves. The sagittal alignment was then compared between the different groups,
      and correlation analysis was also taken between coronal and sagittal parameters.
      Besides, each subject's Roussouly type was decided and its distribution was
      compared among different Lenke types. RESULTS: The cohort included 59 males and
      125 females, averagely aged at 15.5 +/- 3.3 years old. Most sagittal parameters
      except thoracic kyphosis (TK) and pelvic tilt (PT) were similar among different
      Lenke types, while all the sagittal parameters were similar between males and
      females. The groups with different lumbar modifiers had similar sagittal
      parameters except TK, which was also true for the groups with different amounts
      of coronal curves. 42.4 % of the cohort belonged to Roussouly type 3, and the
      distribution of Roussouly types was comparable among all Lenke types. All
      sagittal parameters except C7 translation ratio were significantly different
      among Roussouly types (P < 0.05). Correlation analysis showed that main thoracic
      (MT) was negatively correlated with lumbar lordosis (LL, r = -0.324), sacral
      slope (r = -0.321) and spino-sacral angle (r = -0.363). Partial correlation
      analysis found that thoracolumbar/lumbar was negatively correlated with TK (r = 
      0.464) and LL (r = -0.422) when MT was controlled. CONCLUSIONS: The influence of
      coronal deformity on sagittal parameters was limited and mainly reflected in the
      deviation of TK. Most coronal and sagittal parameters were not significantly
      correlated, and the coronal deformity types did not change the global sagittal
      postural patterns.

PMID- 25957285
TI  - Cervical Cancer Knowledge, Perceptions and Screening Behaviour Among Female
      University Students in Ghana.
AB  - Cervical cancer is becoming a leading cause of death among women in developing
      countries. Nevertheless, little is known regarding knowledge and perception of
      cervical cancer and screening behaviour particularly among female tertiary
      students in Ghana. This study sought to examine the knowledge and perceptions of
      cervical cancer and screening behaviour among female students in the University
      of Cape Coast and Ghana Institute of Management and Public Administration in
      Ghana. A cross-sectional survey design was adopted for the study. Systematic and
      stratified random sampling techniques were used to select 410 participants for
      the study. The study found that the participants lacked knowledge on specific
      risk factors and symptoms of cervical cancer. Also, even though the participants
      had a fair perception of cervical cancer, they had a poor cervical cancer
      screening behaviour. Awareness of cervical cancer was significantly influenced by
      religious affiliation while cervical cancer screening was significantly
      determined by the working status of the participants. Specific knowledge on
      cervical cancer and its risk factors as well as regular screening behaviour is
      paramount to the prevention of cervical cancer. Consequently, the University
      Health Services should focus on promoting regular cervical cancer awareness
      campaigns and screening among the students particularly, females.

PMID- 25957286
TI  - The reporting of clinical signs in laboratory animals: FELASA Working Group
      Report.
AB  - Observing and reporting clinical signs in laboratory animals is necessary for
      many reasons: the assessment of animal welfare, compliance with the principle of
      refinement (e.g. humane endpoints), regulatory compliance (e.g. reporting
      severity) and, importantly, as a scientific outcome, e.g. in animal models of
      disease or safety studies. Developments in the reporting of clinical signs will
      enhance the scientific value gained from animal experiments and further address
      the ethical cost. This paper discusses systematic approaches to the observation
      and reporting of clinical signs in animals (to be) used for research. Glossaries
      from public and corporate institutions have been consulted and a reference
      glossary has been set up, providing terminology to be tailored for institutional
      or project-specific use. The clinical examination of animals must be carried out
      by competent and specifically trained staff in a systematic way and repeated at
      adequate intervals and clinical observations must be registered effectively to
      allow this information to be used. The development of institutional or project
      specific glossaries and the use of handwritten records or automated databases are
      discussed in detail. Among the users are animal care staff, veterinarians and
      researchers who will need to agree on a given set of clinical signs to be
      monitored routinely or as a scientific read-out and to train for the proper
      application. The paper introduces a long list of clinical signs with scientific
      terminology, descriptions and explanations as a reference glossary to be
      published and maintained online as a living document supported by the authors as
      an editorial committee. 

PMID- 25957287
TI  - A Leukemia-Associated CD34/CD123/CD25/CD99+ Immunophenotype Identifies FLT3
      Mutated Clones in Acute Myeloid Leukemia.
AB  - PURPOSE: We evaluated leukemia-associated immunophenotypes (LAIP) and their
      correlation with fms-like tyrosine kinase 3 (FLT3) and nucleophosmin (NPM1) gene
      mutational status in order to contribute a better identification of patients at
      highest risk of relapse in acute myeloid leukemia (AML). EXPERIMENTAL DESIGN:
      Bone marrow samples from 132 patients with AML were analyzed by nine-color
      multiparametric flow cytometry. We confirmed the presence of the mutation in
      diagnostic samples and in sorted cells by conventional RT-PCR and by patient
      specific RQ-PCR. RESULTS: Within the CD34(+) cell fraction, we identified a
      discrete population expressing high levels of the IL3 receptor alpha-chain
      (CD123) and MIC-2 (CD99) in combination with the IL2 receptor alpha-chain (CD25).
      The presence of this population positively correlated with the internal tandem
      duplications (ITD) mutation in the FLT3 gene (r = 0.71). Receiver operating
      characteristics showed that, within the CD34(+) cell fraction a percentage of
      CD123/CD99/CD25(+) cells >=11.7% predicted FLT3-ITD mutations with a specificity
      and sensitivity of >90%. CD34/CD123/CD99/CD25(+) clones were also detectable at
      presentation in 3 patients with FLT3 wild-type/NPM1(+) AML who relapsed with FLT3
      ITD/NPM1(+) AML. Quantitative real-time PCR designed at relapse for each FLT3-ITD
      in these three cases confirmed the presence of low copy numbers of the mutation
      in diagnostic samples. CONCLUSIONS: Our results suggest that the
      CD34/CD25/CD123/CD99(+) LAIP is strictly associated with FLT3-ITD-positive cells.

PMID- 25957289
TI  - Descriptive Epidemiology of Unintentional Burn Injuries Admitted to a Tertiary
      Level Government Hospital in Nepal: Gender-Specific Patterns.
AB  - This study describes the epidemiology of unintentional adult burn injury
      admissions in a tertiary hospital in Nepal, from 2002 to 2013, focusing on gender
      specific patterns. Chi-square tests and Wilcoxon Rank Sum tests were performed.
      There were 819 unintentional burn admissions: 52% were male and 58% younger than
      35 years. The median percentage total body surface area burned (interquartile
      range) was greater in females than in males (P < .001): 28% (17-40) versus 20%
      (12-35), and female mortality was higher (32% vs 11%). A higher proportion
      females were illiterate than males (48% vs 17%). Burns occurred at home (67%),
      work (28%), and public places (5%); gender-specific patterns were observed. Flame
      burns accounted for 77%, electricity 13%, and scalds 8%. Kerosene (31%) and
      biomass (27%) were the major fuels. Cooking, heating, and lighting were the main
      activities associated with burn injury. Results support interventions to reduce
      the use of open fires and kerosene and to promote electrical safety. 

PMID- 25957288
TI  - Spinal Myxopapillary Ependymomas Demonstrate a Warburg Phenotype.
AB  - PURPOSE: Myxopapillary ependymoma (MPE) is a distinct histologic variant of
      ependymoma arising commonly in the spinal cord. Despite an overall favorable
      prognosis, distant metastases, subarachnoid dissemination, and late recurrences
      have been reported. Currently, the only effective treatment for MPE is gross
      total resection. We characterized the genomic and transcriptional landscape of
      spinal ependymomas in an effort to delineate the genetic basis of this disease
      and identify new leads for therapy. EXPERIMENTAL DESIGN: Gene expression
      profiling was performed on 35 spinal ependymomas, and copy number profiling was
      done on an overlapping cohort of 46 spinal ependymomas. Functional validation
      experiments were performed on tumor lysates consisting of assays measuring
      pyruvate kinase M activity (PKM), hexokinase activity (HK), and lactate
      production. RESULTS: At a gene expression level, we demonstrate that spinal grade
      II and MPE are molecularly and biologically distinct. These are supported by
      specific copy number alterations occurring in each histologic variant. Pathway
      analysis revealed that MPE are characterized by increased cellular metabolism,
      associated with upregulation of HIF1alpha. These findings were validated by
      Western blot analysis demonstrating increased protein expression of HIF1alpha,
      HK2, PDK1, and phosphorylation of PDHE1A. Functional assays were performed on MPE
      lysates, which demonstrated decreased PKM activity, increased HK activity, and
      elevated lactate production. CONCLUSIONS: Our findings suggest that MPE may be
      driven by a Warburg metabolic phenotype. The key enzymes promoting the Warburg
      phenotype: HK2, PKM2, and PDK are targetable by small-molecule
      inhibitors/activators, and should be considered for evaluation in future clinical
      trials for MPE.

PMID- 25957290
TI  - Alterations of lung microbiota in a mouse model of LPS-induced lung injury.
AB  - Acute lung injury (ALI) and the more severe acute respiratory distress syndrome
      are common responses to a variety of infectious and noninfectious insults. We
      used a mouse model of ALI induced by intratracheal administration of sterile
      bacterial wall lipopolysaccharide (LPS) to investigate the changes in innate lung
      microbiota and study microbial community reaction to lung inflammation and
      barrier dysfunction induced by endotoxin insult. One group of C57BL/6J mice
      received LPS via intratracheal injection (n = 6), and another received sterile
      water (n = 7). Bronchoalveolar lavage (BAL) was performed at 72 h after
      treatment. Bacterial DNA was extracted and used for qPCR and 16S rRNA gene-tag
      (V3-V4) sequencing (Illumina). The bacterial load in BAL from ALI mice was
      increased fivefold (P = 0.03). The community complexity remained unchanged
      (Simpson index, P = 0.7); the Shannon diversity index indicated the increase of
      community evenness in response to ALI (P = 0.07). Principal coordinate analysis
      and analysis of similarity (ANOSIM) test (P = 0.005) revealed a significant
      difference between microbiota of control and ALI groups. Bacteria from families
      Xanthomonadaceae and Brucellaceae increased their abundance in the ALI group as
      determined by Metastats test (P < 0.02). In concordance with the 16s-tag data,
      Stenotrohomonas maltophilia (Xanthomonadaceae) and Ochrobactrum anthropi
      (Brucellaceae) were isolated from lungs of mice from both groups. Metabolic
      profiling of BAL detected the presence of bacterial substrates suitable for both
      isolates. Additionally, microbiota from LPS-treated mice intensified IL-6-induced
      lung inflammation in naive mice. We conclude that the morbid transformation of
      ALI microbiota was attributed to the set of inborn opportunistic pathogens
      thriving in the environment of inflamed lung, rather than the external infectious
      agents. 

PMID- 25957291
TI  - Plasma gelsolin improves lung host defense against pneumonia by enhancing
      macrophage NOS3 function.
AB  - Plasma gelsolin (pGSN) functions as part of the "extracellular actin-scavenging
      system," but its potential to improve host defense against infection has not been
      studied. In a mouse model of primary pneumococcal pneumonia, recombinant human
      pGSN (rhu-pGSN) caused enhanced bacterial clearance, reduced acute inflammation,
      and improved survival. In vitro, rhu-pGSN rapidly improved lung macrophage uptake
      and killing of bacteria (Streptococcus pneumoniae, Escherichia coli, and
      Francisella tularensis). pGSN triggers activating phosphorylation (Ser(1177)) of
      macrophage nitric oxide synthase type III (NOS3), an enzyme with important
      bactericidal functions in lung macrophages. rhu-pGSN failed to enhance bacterial
      killing by NOS3(-/-) macrophages in vitro or bacterial clearance in NOS3(-/-)
      mice in vivo. Prophylaxis with immunomodulators may be especially relevant for
      patients at risk for secondary bacterial pneumonia, e.g., after influenza.
      Treatment of mice with pGSN challenged with pneumococci on postinfluenza day 7
      (the peak of enhanced susceptibility to secondary infection) caused a ~15-fold
      improvement in bacterial clearance, reduced acute neutrophilic inflammation, and
      markedly improved survival, even without antibiotic therapy. pGSN is a potential
      immunomodulator for improving lung host defense against primary and secondary
      bacterial pneumonia. 

PMID- 25957292
TI  - Linking progression of fibrotic lung remodeling and ultrastructural alterations
      of alveolar epithelial type II cells in the amiodarone mouse model.
AB  - Chronic injury of alveolar epithelial type II cells (AE2 cells) represents a key
      event in the development of lung fibrosis in animal models and in humans, such as
      idiopathic pulmonary fibrosis (IPF). Intratracheal delivery of amiodarone to mice
      results in a profound injury and macroautophagy-dependent apoptosis of AE2 cells.
      Increased autophagy manifested in AE2 cells by disturbances of the intracellular
      surfactant. Hence, we hypothesized that ultrastructural alterations of the
      intracellular surfactant pool are signs of epithelial stress correlating with the
      severity of fibrotic remodeling. With the use of design-based stereology, the
      amiodarone model of pulmonary fibrosis in mice was characterized at the light and
      ultrastructural level during progression. Mean volume of AE2 cells, volume of
      lamellar bodies per AE2 cell, and mean size of lamellar bodies were correlated to
      structural parameters reflecting severity of fibrosis like collagen content.
      Within 2 wk amiodarone leads to an increase in septal wall thickness and a
      decrease in alveolar numbers due to irreversible alveolar collapse associated
      with alveolar surfactant dysfunction. Progressive hypertrophy of AE2 cells and
      increase in mean individual size and total volume of lamellar bodies per AE2 cell
      were observed. A high positive correlation of these AE2 cell-related
      ultrastructural changes and the deposition of collagen fibrils within septal
      walls were established. Qualitatively, similar alterations could be found in IPF
      samples with mild to moderate fibrosis. We conclude that ultrastructural
      alterations of AE2 cells including the surfactant system are tightly correlated
      with the progression of fibrotic remodeling. 

PMID- 25957293
TI  - Combination of erythromycin and dexamethasone improves corticosteroid sensitivity
      induced by CSE through inhibiting PI3K-delta/Akt pathway and increasing GR
      expression.
AB  - Corticosteroid insensitivity, which is induced by cigarette smoke extract (CSE),
      is a significant barrier when treating chronic obstructive pulmonary disease
      (COPD). Erythromycin (EM) has been shown to have an anti-inflammatory role in
      some chronic airway inflammatory diseases, particularly diffuse panbronchiolitis
      and cystic fibrosis. Here, we explored whether the combination therapy of EM and
      dexamethasone (Dex) reverses corticosteroid insensitivity and investigated the
      molecular mechanism by which this occurs. We demonstrated that the combination of
      EM and Dex restored corticosteroid sensitivity in peripheral blood mononuclear
      cells (PBMCs) from COPD patients and U937 cells after CSE exposure. Moreover,
      pretreatment with 10, 50, or 100 MUg/ml EM reversed the HDAC2 protein reduction
      induced by CSE exposure in a dose-dependent manner. U937 cells exposed to CSE
      show a reduction in histone deacetylase (HDAC) activity, which was potently
      reversed by EM or combination treatment. Although 10 and 17.5% CSE increased
      phosphorylated Akt (PAkt) expression in a concentration-dependent manner,
      preapplication of EM and the combination treatment in particular blocked this
      PAkt increase. Total Akt levels were unaffected by CSE or EM treatments.
      Furthermore, the combination treatment enhanced glucocorticoid receptor (GR)alpha
      expression. Our results demonstrate that the combination therapy of EM and Dex
      can restore corticosteroid sensitivity through inhibition of the PI3K-delta/Akt
      pathway and enhancing GRalpha expression. 

PMID- 25957296
TI  - Pseudo-Gaucher Cells in Thalassemia Intermedia.

PMID- 25957297
TI  - Embracing and resisting climate identities in the Australian press: Sceptics,
      scientists and politics.
AB  - This article charts the development of a label that appeared early on in
      Australian debates on climate change, namely 'greenhouse sceptics'. We explore
      who uses the label, for what purposes and with which effects, and how this label
      may contribute to the development of social representations in the climate
      debate. Our findings show that over the last 25 years, 'greenhouse sceptic' has
      been used by journalists and climate scientists to negativize those criticizing
      mainstream climate science, but that it has also been used, even embraced, by
      Australian climate sceptics to label themselves in order to construct a positive
      identity modelled on celebrity sceptics in the United States. We found that the
      label was grounded in religious metaphors that frame mainstream science as a
      catastrophist and alarmist religious cult. Overall, this article provides
      detailed insights into the genealogy of climate scepticism in a particular
      cultural and historical context.

PMID- 25957295
TI  - Nrf2 reduces allergic asthma in mice through enhanced airway epithelial
      cytoprotective function.
AB  - Asthma development and pathogenesis are influenced by the interactions of airway
      epithelial cells and innate and adaptive immune cells in response to allergens.
      Oxidative stress is an important mediator of asthmatic phenotypes in these cell
      types. Nuclear erythroid 2-related factor 2 (Nrf2) is a redox-sensitive
      transcription factor that is the key regulator of the response to oxidative and
      environmental stress. We previously demonstrated that Nrf2-deficient mice have
      heightened susceptibility to asthma, including elevated oxidative stress,
      inflammation, mucus, and airway hyperresponsiveness (AHR) (Rangasamy T, Guo J,
      Mitzner WA, Roman J, Singh A, Fryer AD, Yamamoto M, Kensler TW, Tuder RM, Georas
      SN, Biswal S. J Exp Med 202: 47-59, 2005). Here we dissected the role of Nrf2 in
      lung epithelial cells and tested whether genetic or pharmacological activation of
      Nrf2 reduces allergic asthma in mice. Cell-specific activation of Nrf2 in club
      cells of the airway epithelium significantly reduced allergen-induced AHR,
      inflammation, mucus, Th2 cytokine secretion, oxidative stress, and airway
      leakiness and increased airway levels of tight junction proteins zonula occludens
      1 and E-cadherin. In isolated airway epithelial cells, Nrf2 enhanced epithelial
      barrier function and increased localization of zonula occludens-1 to the cell
      surface. Pharmacological activation of Nrf2 by 2-trifluoromethyl-2'
      methoxychalone during the allergen challenge was sufficient to reduce allergic
      inflammation and AHR. New therapeutic options are needed for asthma, and this
      study demonstrates that activation of Nrf2 in lung epithelial cells is a novel
      potential therapeutic target to reduce asthma susceptibility. 

PMID- 25957294
TI  - Role of macrophage migration inhibitory factor in age-related lung disease.
AB  - The prevalence of many common respiratory disorders, including pneumonia, chronic
      obstructive lung disease, pulmonary fibrosis, and lung cancer, increases with
      age. Little is known of the host factors that may predispose individuals to such
      diseases. Macrophage migration inhibitory factor (MIF) is a potent upstream
      regulator of the immune system. MIF is encoded by variant alleles that occur
      commonly in the population. In addition to its role as a proinflammatory
      cytokine, a growing body of literature demonstrates that MIF influences diverse
      molecular processes important for the maintenance of cellular homeostasis and may
      influence the incidence or clinical manifestations of a variety of chronic lung
      diseases. This review highlights the biological properties of MIF and its
      implication in age-related lung disease. 

PMID- 25957298
TI  - Still stressed but feeling better: Well-being in autism spectrum disorder
      families as children become adults.
AB  - The transition to adulthood and adulthood itself have been identified as times of
      stress for parents of individuals with autism spectrum disorder. Longitudinal
      studies, however, show improvements in the well-being of mothers of adolescents
      and young adults with autism spectrum disorder. This article presents a cross
      sectional study of 102 Spanish parents (51 mothers and 51 fathers) of 102
      individuals with autism spectrum disorder. The aim was to examine parental well
      being (evaluated based on stress, anxiety, depression and psychological well
      being) in three groups of parents of adults, adolescents and young children with
      autism spectrum disorder. In addition, the relationships between parental well
      being and the characteristics of their children, social support, parental age and
      sense of coherence were analysed. The results showed that although parental
      stress and psychological well-being levels were similar across the groups,
      depression and anxiety were lower in parents of adolescents or adults compared
      with parents of young children. Different factors predicted different measures of
      parental well-being, but sense of coherence emerged as the main predictive factor
      for all parental well-being measures. These findings are discussed in relation to
      parental adaptation over the lifespan and the implications for interventions in
      autism spectrum disorder families. 

PMID- 25957299
TI  - Conscientious objection: personal and professional ethics in the public square.
AB  - English law expects health professionals to have, and act upon, consciences, but
      formal conscience clauses are not the main legal recognition of this expectation.
      Rather, they should be regarded as an anomaly with roots in very specific
      political settlements between society and health professions, whose legitimacy is
      historically contingent, and as an aspect of the 'price' to be paid for securing
      services. There are sound reasons for the protection of conscientious discretion
      as an aspect of professional identify, but specific rights of personal
      conscientious objection are difficult to reconcile with legitimate public
      expectations of comprehensive and non-discriminatory services. Professional
      identities include moral commitments, such as the privileging of patient safety
      over administrative convenience. These should not be permitted to be overridden
      by personal moralities during the course of service delivery (as opposed to
      debating in the abstract what the proper courses of action should be).
      Consequently, formal conscientious objection clauses should be reduced to a
      minimum and regularly revisited. It is generally more satisfactory to address
      clashes between the personal moralities of professionals and public expectations
      through more flexible means, enabling accommodation of a plurality of views where
      possible but acknowledging that this is a matter of striking an appropriate
      balance. Employment law rather than healthcare law provides the best mechanism
      for regulating this process. 

PMID- 25957300
TI  - Voices of discontent? Conscience, compromise, and assisted dying.
AB  - If some form of assisted dying is to be legalised, we are likely to hear voices
      of discontent, not least from the medical profession and some of its members, who
      might be expected to provide the service. The profession generally favours a
      position of opposition, premised on an ethic of 'caring not killing', which might
      be said to convey its 'professional conscience'. There will, of course, also be
      individual conscientious objectors. In this article, we initially explore the
      nature and sources of conscience and we argue that conscience does merit respect.
      We also recognise that professionals, qua professionals, are bound to serve their
      patients, some of whom will want (and may be entitled to) that which their
      doctors do not wish to provide. Reflecting on the different values in issue, we
      suggest that there is a case for principled compromise which would afford
      professionals a limited right to conscientiously object, while also protecting
      patients. We then relate these reflections to assisted dying specifically. In the
      absence of any definitive steer from the purported integrity of medicine, we
      suspect that the profession could adopt a neutral stance on this divisive issue.
      We nevertheless anticipate individual objections if the law does move to embrace
      assisted dying, and we argue that such objections should be respected, according
      to the terms of the compromise model we defend. 

PMID- 25957301
TI  - Total cost and cost predictors in systemic lupus erythematosus - 8-years follow
      up of a Swedish inception cohort.
AB  - OBJECTIVE: To study the annual direct and indirect costs in systemic lupus
      erythematosus (SLE) and how age, disease manifestations, disease activity, and
      organ damage influence total costs and predicted costs for SLE. METHODS: Clinical
      data on all patients with a diagnosis of SLE living in a defined area in southern
      Sweden during eight years were linked to health authority registries and the
      social insurance system which contain data on cost. Cost data on four matched
      population controls for each patient were also extracted. The controls were
      matched for age, sex, and area of residence. RESULTS: Data from 127 patients with
      SLE and 508 population controls were extracted. The mean annual total cost for
      SLE patients was SEK 180,520 ($30,093); the highest costs were found in the
      subgroup with nephritis SEK 229,423 ($38,246). The total costs for the patient
      group were significantly higher (p < 0.05) compared to the population controls of
      SEK 59,985 ($10,000). Of the total costs, 72% were due to indirect costs, 3% to
      SLE-specific pharmaceuticals, and the remaining 25% were in- and outpatient
      related costs. During the study period, inpatient days decreased by 60%, while
      outpatient contacts increased by 25%. Age (inverse relation), increasing disease
      activity, and acquired organ damage were significant predictors of total costs
      (all p < 0.05). CONCLUSION: The total annual costs for unselected SLE patients
      were found to be three times those for matched population controls. Important
      predictors of total costs were found.

PMID- 25957302
TI  - Subcellular size.
AB  - All of the same conceptual questions about size in organisms apply equally at the
      level of single cells. What determines the size, not only of the whole cell, but
      of all of its parts? What ensures that subcellular components are properly
      proportioned relative to the whole cell? How does alteration in organelle size
      affect biochemical function? Answering such fundamental questions requires us to
      understand how the size of individual organelles and other cellular structures is
      determined. Knowledge of organelle biogenesis and dynamics has advanced rapidly
      in recent years. Does this knowledge give us enough information to formulate
      reasonable models for organelle size control, or are we still missing something? 

PMID- 25957304
TI  - Retracting Soft Tissue in Minimally Invasive Hip Arthroplasty Using a Robotic
      Arm: A Comparison Between a Semiactive Retractor Holder and Human Assistants in a
      Cadaver Study.
AB  - BACKGROUND: All surgical procedures in orthopedics involve the retraction of soft
      tissue. In this study, the performance of 3 assistants holding the medial
      retractor during minimally invasive hip arthroplasty was compared with a
      semiactive retractor holder in a cadaver setup. METHODS: A total of 40
      measurements on 3 cadavers were carried out with each subject (3 human, 1 robot)
      measuring each cadaver 10 times. The retractor was equipped with a sensor array
      on both sides, to measure variations of the retracting pressures over a 2-minute
      interval. RESULTS: The semiactive retractor holder showed an almost constant
      performance compared with the test subjects. There was no significant reduction
      of the applied pressure and almost no variation during the 2-minute interval and
      across all measurements. CONCLUSIONS: The performance of the semiactive retractor
      holder was more stable than that of a human assistant, making it suitable for
      intraoperative usage.

PMID- 25957303
TI  - Schwann Cells: Development and Role in Nerve Repair.
AB  - Schwann cells develop from the neural crest in a well-defined sequence of events.
      This involves the formation of the Schwann cell precursor and immature Schwann
      cells, followed by the generation of the myelin and nonmyelin (Remak) cells of
      mature nerves. This review describes the signals that control the embryonic phase
      of this process and the organogenesis of peripheral nerves. We also discuss the
      phenotypic plasticity retained by mature Schwann cells, and explain why this
      unusual feature is central to the striking regenerative potential of the
      peripheral nervous system (PNS). 

PMID- 25957305
TI  - The presence of brain white matter lesions in relation to preeclampsia and
      migraine.
AB  - INTRODUCTION: Identifying female-specific risk markers for cerebrovascular
      disease is becoming increasingly important. Both migraine and preeclampsia have
      been associated with higher incidence of brain white matter lesions (WML) and
      stroke. We assessed the association between WML and migraine among formerly
      (pre)eclamptic women. METHODS: A total of 118 women (76 formerly (pre)eclamptic
      and 42 control women) were screened for migraine and WML presence. Independent
      effects of migraine and (pre)eclampsia on WML were assessed. RESULTS: Migraine
      prevalence did not differ between the (pre)eclamptic (26/76; 34%); and control
      group (10/42; 24%), p = 0.17. Age-adjusted regression analysis failed to show a
      significant independent effect of migraine (OR 1.14; 95% CI 0.47-2.76; p = 0.77)
      on WML presence, and showed a non-significant effect of (pre)eclampsia (OR 2.30;
      95% CI 0.90-5.83; p = 0.08). CONCLUSION: Migraine prevalence was not found to be
      an independent risk factor for WML prevalence in formerly (pre)eclamptic women.
      Since this study had a small sample size, larger prospective studies are needed
      to examine female-specific risk factors for WML and its consequences.

PMID- 25957307
TI  - Th17 polarization of memory Th cells in early arthritis: the vasoactive
      intestinal peptide effect.
AB  - Several studies in humans indicate the implication of Th17 cells in RA. Therapies
      targeting their pathogenicity, as well as their plasticity to the Th17/1
      phenotype, could ameliorate the progression of the pathology. The neuroendocrine
      environment has a major impact on the differentiation of lymphoid cells. VIP is
      present in the microenvironment of the joint, and its known therapeutic effects
      are supported by several studies on RA. We examine the ability of VIP to modulate
      the differentiation of Th17 cells. Peripheral blood CD4(+)CD45RO(+) T cells from
      HD and eRA patients were expanded under Th17-polarizing conditions in the
      presence of TGF-beta. After 7 days, the higher IL-17A, IL-21, and IL-9 levels and
      lower IL-22 levels indicate the nonpathogenic profile for Th17 cells in HD. In
      contrast, Th17 cells from eRA patients produced significantly more IL-22 and IFN
      gamma, and these cells show a more Th17/1 profile, indicating a pathogenic
      phenotype. Interestingly, when VIP was present in the Th17 conditioned medium,
      increased levels of IL-10 and IL-9 were detected in HD and eRA patients. VIP also
      reduced the levels of IL-22 in eRA patients. These data suggest that VIP reduces
      the pathogenic profile of the Th17-polarized cells. This effect was accompanied
      by an increased in the Treg/Th17 profile, as shown by the increase levels of
      Foxp3. In conclusion, this report addresses a novel and interesting question on
      the effect of VIP on human Th17 cells and adds clinical relevance by analyzing,
      in parallel, HD and eRA patients. 

PMID- 25957306
TI  - CCR5 susceptibility to ligand-mediated down-modulation differs between human T
      lymphocytes and myeloid cells.
AB  - CCR5 is a chemokine receptor expressed on leukocytes and a coreceptor used by HIV
      1 to enter CD4(+) T lymphocytes and macrophages. Stimulation of CCR5 by
      chemokines triggers internalization of chemokine-bound CCR5 molecules in a
      process called down-modulation, which contributes to the anti-HIV activity of
      chemokines. Recent studies have shown that CCR5 conformational heterogeneity
      influences chemokine-CCR5 interactions and HIV-1 entry in transfected cells or
      activated CD4(+) T lymphocytes. However, the effect of CCR5 conformations on
      other cell types and on the process of down-modulation remains unclear. We used
      mAbs, some already shown to detect distinct CCR5 conformations, to compare the
      behavior of CCR5 on in vitro generated human T cell blasts, monocytes and MDMs
      and CHO-CCR5 transfectants. All human cells express distinct antigenic forms of
      CCR5 not detected on CHO-CCR5 cells. The recognizable populations of CCR5
      receptors exhibit different patterns of down-modulation on T lymphocytes compared
      with myeloid cells. On T cell blasts, CCR5 is recognized by all antibodies and
      undergoes rapid chemokine-mediated internalization, whereas on monocytes and
      MDMs, a pool of CCR5 molecules is recognized by a subset of antibodies and is not
      removed from the cell surface. We demonstrate that this cell surface-retained
      form of CCR5 responds to prolonged treatment with more-potent chemokine analogs
      and acts as an HIV-1 coreceptor. Our findings indicate that the regulation of
      CCR5 is highly specific to cell type and provide a potential explanation for the
      observation that native chemokines are less-effective HIV-entry inhibitors on
      macrophages compared with T lymphocytes. 

PMID- 25957309
TI  - Hospital standardised mortality ratios--their use and misuse.

PMID- 25957308
TI  - Genetic and cellular dissection of the activation of AM14 rheumatoid factor B
      cells in a mouse model of lupus.
AB  - The RF-specific AM14 tg BCR has been used as a model to dissect the mechanisms of
      B cell tolerance to ICs containing nucleic acids. We have shown previously that
      AM14 RF B cells break tolerance in the TC mouse model of lupus through the dual
      engagement of the AM14 BCR and TLR9. In this study, we showed that neither the
      expression of Sle1 or Sle2 susceptibility loci alone was sufficient to activate
      AM14 RF B cells, suggesting that the production of antichromatin IgG2a(a) autoAg
      mediated by Sle1 and an intrinsically higher B cell activation mediated by Sle2
      were required. We also showed that the B6 genetic background enhanced the
      selection of AM14 RF B cells to the MZB cell compartment regardless of the
      expression of the Sle loci and therefore, of their activation into AFCs.
      Furthermore, some AM14 RF B cells were selected into the B-1a compartment, where
      they did not differentiate into AFCs. Therefore, it is unlikely that the
      selection of AM14 RF B cells to the MZB or B-1a cell compartments in TC.AM14(a)
      mice is responsible for their breach of tolerance. Finally, we showed that the
      presence of expression of Sle1 in non-tg cells, most likely T cells, is necessary
      for the activation of AM14 RF B cells into AFCs. Overall, these results suggest a
      threshold model of activation of AM14 RF B cells on the B6 background with
      additive genetic and cellular contribution of multiple sources. 

PMID- 25957310
TI  - Characterization of the inflammatory phenotype of Mycobacterium avium subspecies
      paratuberculosis using a novel cell culture passage model.
AB  - Understanding the pathogenic mechanisms of Mycobacterium avium subspecies
      paratuberculosis (MAP) and the host responses to Johne's disease is complicated
      by the multi-faceted disease progression, late-onset host reaction and the lack
      of available ex vivo infection models. We describe a novel cell culture passage
      model that mimics the course of infection in vivo. The developed model simulates
      the interaction of MAP with the intestinal epithelial cells, followed by
      infection of macrophages and return to the intestinal epithelium. MAP
      internalization triggers a minimal inflammatory response. After passage through a
      macrophage phase, bacterial reinfection of MDBK epithelial cells, representing
      the late phase of intestinal mucosal infection, is associated with increased
      synthesis of the pro-inflammatory transcripts of IL-6, CCL5, IL-8 and IL-18,
      paired with decreased levels of TGFbeta. Transcriptome analysis of MAP from each
      stage of epithelial cell infection identified increased expression of lipid
      biosynthesis and lipopeptide modification genes in the inflammatory phenotype of
      MAP. Total lipid analysis by HPLC-ES/MS indicates different lipidomic profiles
      between the two phenotypes and a unique set of lipids composing the inflammatory
      MAP phenotype. The presence of selected upregulated lipid-modification gene
      transcripts in samples of ileal tissue from cows diagnosed with Johne's disease
      supports and validates the model. By using the relatively simple cell culture
      passage model, we show that MAP alters its lipid composition during intracellular
      infection and acquires a pro-inflammatory phenotype, which likely is associated
      with the inflammatory phase of Johne's disease. 

PMID- 25957311
TI  - Experimental evolution can unravel the complex causes of natural selection in
      clinical infections.
AB  - It is increasingly clear that rapid evolutionary dynamics are an important
      process in microbial ecology. Experimental evolution, wherein microbial evolution
      is observed in real-time, has revealed many instances of appreciable evolutionary
      change occurring on very short timescales of a few days or weeks in response to a
      variety of biotic and abiotic selection pressures. From clinical infections,
      including the chronic bacterial lung infections associated with cystic fibrosis
      that form a focus of my research, there is now abundant evidence suggesting that
      rapid evolution by infecting microbes contributes to host adaptation, treatment
      failure and worsening patient prognosis. However, disentangling the drivers of
      natural selection in complex infection environments is extremely challenging and
      limits our understanding of the selective pressures acting upon microbes in
      infections. Controlled evolution experiments can make a vital contribution to
      this by determining the causal links between predicted drivers of natural
      selection and the evolutionary responses of microbes. Integration of experimental
      evolution into studies of clinical infections is a key next step towards a better
      understanding of the causes and consequences of rapid microbial evolution in
      infections, and discovering how these evolutionary processes might be influenced
      to improve patient health.A video of this Prize Lecture, presented at the Society
      for General Microbiology Annual Conference 2015, can be viewed via this link:
      Michael A. Brockhurst https://www.youtube.com/watch?v=N1bodVSl27E. 

PMID- 25957312
TI  - Validation of multilevel regression and poststratification methodology for small
      area estimation of health indicators from the behavioral risk factor surveillance
      system.
AB  - Small area estimation is a statistical technique used to produce reliable
      estimates for smaller geographic areas than those for which the original surveys
      were designed. Such small area estimates (SAEs) often lack rigorous external
      validation. In this study, we validated our multilevel regression and
      poststratification SAEs from 2011 Behavioral Risk Factor Surveillance System data
      using direct estimates from 2011 Missouri County-Level Study and American
      Community Survey data at both the state and county levels. Coefficients for
      correlation between model-based SAEs and Missouri County-Level Study direct
      estimates for 115 counties in Missouri were all significantly positive (0.28 for
      obesity and no health-care coverage, 0.40 for current smoking, 0.51 for diabetes,
      and 0.69 for chronic obstructive pulmonary disease). Coefficients for correlation
      between model-based SAEs and American Community Survey direct estimates of no
      health-care coverage were 0.85 at the county level (811 counties) and 0.95 at the
      state level. Unweighted and weighted model-based SAEs were compared with direct
      estimates; unweighted models performed better. External validation results
      suggest that multilevel regression and poststratification model-based SAEs using
      single-year Behavioral Risk Factor Surveillance System data are valid and could
      be used to characterize geographic variations in health indictors at local levels
      (such as counties) when high-quality local survey data are not available. 

PMID- 25957315
TI  - Population structure and genetic diversity of the perennial medicinal shrub
      Plumbago.
AB  - Knowledge of the natural genetic variation and structure in a species is
      important for developing appropriate conservation strategies. As genetic
      diversity analysis among and within populations of Plumbago zeylanica remains
      unknown, we aimed (i) to examine the patterns and levels of morphological and
      genetic variability within/among populations and ascertain whether these
      variations are dependent on geographical conditions; and (ii) to evaluate genetic
      differentiation and population structure within the species. A total of 130
      individuals from 13 populations of P. zeylanica were collected, covering the
      entire distribution area of species across India. The genetic structure and
      variation within and among populations were evaluated using inter-simple sequence
      repeat (ISSR) and randomly amplified DNA polymorphism (RAPD) markers. High levels
      of genetic diversity and significantly high genetic differentiation were revealed
      by both the markers among all studied populations. High values of among
      population genetic diversity were found, which accounted for 60 % of the total
      genetic variance. The estimators of genetic diversity were higher in northern and
      eastern populations than in southern and western populations indicating the
      possible loss of genetic diversity during the spread of this species to Southern
      India. Bayesian analysis, unweighted pair group method with arithmetic average
      cluster analysis and principal coordinates analysis all showed similar results. A
      significant isolation-by-distance pattern was revealed in P. zeylanica by ISSR (r
      = 0.413, P = 0.05) and RAPD (r = 0.279, P = 0.05) analysis. The results obtained
      suggest an urgent need for conservation of existing natural populations along
      with extensive domestication of this species for commercial purpose. 

PMID- 25957313
TI  - Confrontation, Consolidation, and Recognition: The Oocyte's Perspective on the
      Incoming Sperm.
AB  - From the oocyte's perspective, the incoming sperm poses a significant challenge.
      Despite (usually) arising from a male of the same species, the sperm is a
      "foreign" body that may carry with it additional, undesirable factors such as
      transposable elements (mainly retroposons) into the egg. These factors can arise
      either during spermatogenesis or while the sperm is moving through the epididymis
      or the female genital tract. Furthermore, in addition to the paternal genome, the
      sperm also carries its own complex repertoire of RNAs into the egg that includes
      mRNAs, lncRNAs, and sncRNAs. Last, the paternal genome itself is efficiently
      packaged into a protamine (nucleo-toroid) and histone (nucleosome)-based
      chromatin scaffold within which much of the RNA is embedded. Taken together, the
      sperm delivers a far more complex package to the egg than was originally thought.
      Understanding this complexity, at both the compositional and structural level,
      depends largely on investigating sperm chromatin from both the genomic (DNA
      packaging) and epigenomic (RNA carriage and extant histone modifications)
      perspectives. Why this complexity has arisen and its likely purpose requires us
      to look more closely at what happens in the oocyte when the sperm gains entry and
      the processes that then take place preparing the paternal (and maternal) genomes
      for syngamy. 

PMID- 25957314
TI  - Mycobacterial Growth.
AB  - In this work, we review progress made in understanding the molecular
      underpinnings of growth and division in mycobacteria, concentrating on work
      published since the last comprehensive review ( Hett and Rubin 2008). We have
      focused on exciting work making use of new time-lapse imaging technologies
      coupled with reporter-gene fusions and antimicrobial treatment to generate
      insights into how mycobacteria grow and divide in a heterogeneous manner. We try
      to reconcile the different observations reported, providing a model of how they
      might fit together. We also review the topic of mycobacterial spores, which has
      generated considerable discussion during the last few years. Resuscitation
      promoting factors, and regulation of growth and division, have also been actively
      researched, and we summarize progress in these areas. 

PMID- 25957316
TI  - Testing models for the leaf economics spectrum with leaf and whole-plant traits
      in Arabidopsis thaliana.
AB  - The leaf economics spectrum (LES) describes strong relationships between multiple
      functional leaf traits that determine resource fluxes in vascular plants. Five
      models have been proposed to explain these patterns: two based on patterns of
      structural allocation, two on venation networks and one on resource allocation to
      cell walls and cell contents. Here we test these models using data for leaf and
      whole-plant functional traits. We use structural equation modelling applied to
      multiple ecotypes, recombinant inbred lines, near isogenic lines and vascular
      patterning mutants of Arabidopsis thaliana that express LES trait variation. We
      show that a wide variation in multiple functional traits recapitulates the LES at
      the whole-plant scale. The Wright et al. (2004) model and the Blonder et al.
      (2013) venation network model cannot be rejected by data, while two simple models
      and the Shipley et al. (2006) allocation model are rejected. Venation networks
      remain a key hypothesis for the origin of the LES, but simpler explanations also
      cannot be ruled out. 

PMID- 25957317
TI  - Sex-Chromosome Homomorphy in Palearctic Tree Frogs Results from Both Turnovers
      and X-Y Recombination.
AB  - Contrasting with birds and mammals, poikilothermic vertebrates often have
      homomorphic sex chromosomes, possibly resulting from high rates of sex-chromosome
      turnovers and/or occasional X-Y recombination. Strong support for the latter
      mechanism was provided by four species of European tree frogs, which inherited
      from a common ancestor (~ 5 Ma) the same pair of homomorphic sex chromosomes
      (linkage group 1, LG1), harboring the candidate sex-determining gene Dmrt1. Here,
      we test sex linkage of LG1 across six additional species of the Eurasian Hyla
      radiation with divergence times ranging from 6 to 40 Ma. LG1 turns out to be sex
      linked in six of nine resolved cases. Mapping the patterns of sex linkage to the
      Hyla phylogeny reveals several transitions in sex-determination systems within
      the last 10 My, including one switch in heterogamety. Phylogenetic trees of DNA
      sequences along LG1 are consistent with occasional X-Y recombination in all
      species where LG1 is sex linked. These patterns argue against one of the main
      potential causes for turnovers, namely the accumulation of deleterious mutations
      on nonrecombining chromosomes. Sibship analyses show that LG1 recombination is
      strongly reduced in males from most species investigated, including some in which
      it is autosomal. Intrinsically low male recombination might facilitate the
      evolution of male heterogamety, and the presence of important genes from the sex
      determination cascade might predispose LG1 to become a sex chromosome.

PMID- 25957319
TI  - UK child survival in a European context: recommendations for a national Countdown
      Collaboration.

PMID- 25957320
TI  - Neonatal screening for hereditary tyrosinaemia: are we there yet?

PMID- 25957318
TI  - Soup to Tree: The Phylogeny of Beetles Inferred by Mitochondrial Metagenomics of
      a Bornean Rainforest Sample.
AB  - In spite of the growth of molecular ecology, systematics and next-generation
      sequencing, the discovery and analysis of diversity is not currently integrated
      with building the tree-of-life. Tropical arthropod ecologists are well placed to
      accelerate this process if all specimens obtained through mass-trapping, many of
      which will be new species, could be incorporated routinely into phylogeny
      reconstruction. Here we test a shotgun sequencing approach, whereby mitochondrial
      genomes are assembled from complex ecological mixtures through mitochondrial
      metagenomics, and demonstrate how the approach overcomes many of the taxonomic
      impediments to the study of biodiversity. DNA from approximately 500 beetle
      specimens, originating from a single rainforest canopy fogging sample from
      Borneo, was pooled and shotgun sequenced, followed by de novo assembly of
      complete and partial mitogenomes for 175 species. The phylogenetic tree obtained
      from this local sample was highly similar to that from existing mitogenomes
      selected for global coverage of major lineages of Coleoptera. When all sequences
      were combined only minor topological changes were induced against this reference
      set, indicating an increasingly stable estimate of coleopteran phylogeny, while
      the ecological sample expanded the tip-level representation of several lineages.
      Robust trees generated from ecological samples now enable an evolutionary
      framework for ecology. Meanwhile, the inclusion of uncharacterized samples in the
      tree-of-life rapidly expands taxon and biogeographic representation of lineages
      without morphological identification. Mitogenomes from shotgun sequencing of
      unsorted environmental samples and their associated metadata, placed robustly
      into the phylogenetic tree, constitute novel DNA "superbarcodes" for testing
      hypotheses regarding global patterns of diversity. 

PMID- 25957321
TI  - A new pathway in the control of the initiation of puberty: the MKRN3 gene.
AB  - Pubertal timing is influenced by complex interactions among genetic, nutritional,
      environmental, and socioeconomic factors. The role of MKRN3, an imprinted gene
      located in the Prader-Willi syndrome critical region (chromosome 15q11-13), in
      pubertal initiation was first described in 2013 after the identification of
      deleterious MKRN3 mutations in five families with central precocious puberty
      (CPP) using whole-exome sequencing analysis. Since then, additional loss-of
      function mutations of MKRN3 have been associated with the inherited premature
      sexual development phenotype in girls and boys from different ethnic groups. In
      all of these families, segregation analysis clearly demonstrated autosomal
      dominant inheritance with complete penetrance, but with exclusive paternal
      transmission, consistent with the monoallelic expression of MKRN3 (a maternally
      imprinted gene). Interestingly, the hypothalamic Mkrn3 mRNA expression pattern in
      mice correlated with a putative inhibitory input on puberty initiation. Indeed,
      the initiation of puberty depends on a decrease in factors that inhibit the
      release of GnRH combined with an increase in stimulatory factors. These recent
      human and animal findings suggest that MKRN3 plays an inhibitory role in the
      reproductive axis to represent a new pathway in pubertal regulation. 

PMID- 25957322
TI  - Determinants of intravaginal practices among HIV-infected women in Zambia using
      conjoint analysis.
AB  - Intravaginal practices (IVPs) are associated with an increased risk of bacterial
      vaginosis and may play a role in HIV transmission. The objective of this study
      was to identify the importance of factors underlying the decision to engage in
      IVP using conjoint analysis; a novel statistical technique used to quantify
      health-related decisions. This study was a cross-sectional study. HIV-infected
      women in Zambia completed audio computer-administered self-interview
      questionnaires assessing demographic, risk factors and IVPs. Reasons for engaging
      in IVPs were explored using conjoint questionnaires. Conjoint analysis was used
      to identify the relative importance of factors for engaging in IVPs. Results of
      the conjoint analysis demonstrated that hygiene was the most important reason for
      engaging in IVPs (mean importance score = 61, SD = 24.3) followed by partner's
      preference (mean importance score = 20, SD = 14.4) and health (mean importance
      score = 17, SD = 13.5). When making the decision to engage in IVPs, women rank
      the importance of hygiene, partner preference and health differently, according
      to their personal characteristics. The use of conjoint analysis to define the
      characteristics of women more likely to engage in specific practices should be
      used to develop tailored rather than standardised IVP interventions, and such
      interventions should be incorporated into clinical practice and women's health
      programmes. 

PMID- 25957323
TI  - Impact of HIV infection on tuberculous pleural effusion.
AB  - The nature of tuberculosis (TB), being one of the most common opportunistic
      infections, is different among HIV-infected patients than HIV-negative patients.
      A retrospective study was conducted on HIV-positive and HIV-negative patients
      with new TB pleural effusion who were admitted to the National Research Institute
      of Tuberculosis and Lung Diseases in Tehran, Iran from 2005 to 2012. The two
      groups were compared with respect to clinical, imaging, mycobacteriologic and
      histopathologic characteristics of TB pleural effusion. In all, 42 HIV-positive
      and 132 HIV-negative cases of TB pleural effusion were included. Bilateral
      pleural effusion was statistically more common in the HIV-positive group (p =
      0.004, OR = 3.81, 95% CI: 1.46-9.94) without any correlation with CD4 cell count.
      Pulmonary infiltration was found in 81% of HIV-positive and 49.2% of HIV-negative
      patients (p = 0.001, OR = 4.38, 95% CI: 1.88-10.1). Mycobacteriologic studies led
      to the diagnosis of TB in 66.6% of HIV-infected and 49.2% of HIV-negative
      patients. In 23.8% of HIV-positive and 50.7% of HIV-negative patients TB was
      ultimately diagnosed by pleural biopsy. HIV remained significantly associated
      with positive culture of pleural fluid in multivariate analysis. The diagnostic
      approach to TB pleural effusion in HIV-infected patients may be different. The
      diagnostic yield of mycobacteriologic studies was higher among HIV-positive
      patients, which may help in reducing the need for invasive procedures like
      pleural biopsy.

PMID- 25957324
TI  - Prevalence and risk factors of cervical squamous intraepithelial lesions among
      HIV-infected women in Dar es Salaam, Tanzania.
AB  - To determine the prevalence and predictors of cervical squamous intraepithelial
      lesions (SIL) among HIV-infected women in Tanzania, a cross-sectional study was
      conducted among HIV-infected women at HIV care and treatment clinics. A
      Papanicolaou (Pap) smear was used as a screening tool for detection of cervical
      SIL. From December 2006 to August 2009, 1365 HIV-infected women received cervical
      screening. The median age was 35 (interquartile range [IQR]: 30-42) years, and
      the median CD4 + cell count was 164 (IQR: 80-257) cells/mm(3). The prevalence of
      cervical SIL was 8.7% (119/1365). In multivariate analysis, older age (>=50
      versus 30-<40 years: prevalence ratio [PR], 2.36; 95% confidence interval [CI],
      1.45-3.84, p for trend = 0.001), lower CD4 + cell counts (<100 versus >=200
      cells/mm(3): PR, 1.55; 95% CI, 1.01-2.36, p for trend = 0.03) and cervical
      inflammation (PR, 1.73; 95% CI, 1.16-2.60, p = 0.008) were associated with an
      increased risk of cervical SIL. Women with advanced WHO HIV disease stage (IV
      versus I/II: PR, 3.45; 95% CI, 1.35-8.85, p for trend = 0.01) had an increased
      risk for high-grade SIL. In resource-limited settings where it is not feasible to
      provide cervical cancer prevention services to all HIV-infected women, greater
      efforts should focus on scaling-up services among those who are older than 50
      years, with lower CD4 cell counts and advanced HIV disease stage. 

PMID- 25957325
TI  - Use of aspirin and statins for the primary prevention of myocardial infarction
      and stroke in patients with human immunodeficiency virus infection.
AB  - This retrospective, cross-sectional study evaluated whether HIV-infected patients
      received aspirin and statins for the primary prevention of myocardial infarction
      and stroke. Among the 258 patients included, 50.4% (n = 130/258) of the patients
      had a high risk of myocardial infarction and 14% (n = 36/258) of stroke. Overall,
      43.1% (n = 56/130) and 50% (n = 18/36) of the patients were prescribed aspirin
      for the primary prevention of myocardial infarction and stroke, respectively.
      Among the patients who required statin therapy, 42.5% (n = 34/80) and 37.1% (n =
      13/35) of patients received it for the primary prevention of myocardial
      infarction and stroke, respectively. The patients who had hypertension (odds
      ratio 3.8, 95% confidence interval 1.5-10.9) and diabetes mellitus (odds ratio
      5.6, 95% confidence interval 2.6-12.4) were more likely to receive aspirin.
      Interventions are needed to improve provider awareness of the use of aspirin and
      statins in the primary prevention of myocardial infarction and stroke in HIV
      infected patients. 

PMID- 25957326
TI  - Rectal chlamydia infection in women at high risk of chlamydia attending Canberra
      Sexual Health Centre.
AB  - Chlamydia is the most commonly notified sexually transmitted infection in
      Australia. Australian guidelines recommend urogenital screening in asymptomatic
      men and women, and rectal screening in men who have sex with men or women
      reporting anal sex/symptoms. International studies describe a rectal chlamydia
      prevalence in women of 5% to 21%. We found that in women at high risk of
      chlamydia, 57% (32/56) tested positive for rectal chlamydia. Of these, 97%
      (31/32) had concurrent urogenital chlamydia. Women with urogenital chlamydia were
      significantly more likely to have a positive rectal result (chi(2), p = 0.000).
      Neither anal symptoms nor reported anal sex were associated with a positive
      rectal chlamydia test. The recommended treatment of rectal chlamydia differs
      substantially from that of urogenital chlamydia, raising the possibility that
      Australian women are being regularly undertreated due to a lack of rectal
      testing. Untreated rectal chlamydia may increase the risk of persistent
      infection, reproductive tract reinfection, complications and transmission.
      Further work is needed to determine the optimal management of chlamydia in women.

PMID- 25957327
TI  - Prevalence and correlates of Trichomonas vaginalis infection among female sex
      workers in a city in Yunnan Province, China.
AB  - Sexual transmission is the fastest growing route of HIV transmission in China,
      and Trichomonas vaginalis(TV) can facilitate HIV transmission and acquisition.
      Our goal was to determine the prevalence and correlates of TV infection among
      female sex workers (FSWs). This cross-sectional study was conducted in a city of
      Yunnan Province in southern China, with confidential face-to-face interviews and
      laboratory tests for TV (wet mount) and other sexually transmitted infections. A
      total of 734 FSWs participated in the study. The prevalence of TV was 9.0% (95%
      confidence interval [CI] 7.02-11.30). In multivariate analyses, adjusted odds
      ratios of TV infection were 3.0 (95% CI 1.47-6.01) for herpes simplex virus type
      2 seropositive, 2.4 (95% CI 1.37-4.14) for Chlamydia trachomatis infection, 2.6
      (95% CI 1.30-5.31) for genital ulcer, 1.9 (95% CI 1.11-3.30) for starting age in
      commercial sex <20 years, and 0.5 (95% CI 0.27-0.87) for vaginal douching. We
      found a relatively high prevalence of TV infection among FSWs in Yunnan Province.
      A range of control strategies that include TV screening are recommended among
      FSWs, which could contribute significantly to the disruption of transmission by
      the provision of immediate treatment.

PMID- 25957328
TI  - Reply to the letter to the editor 'ALK FISH rearranged and amplified tumor with
      negative immunohistochemistry: a rare and challenging case concerning ALK status
      screening in lung cancer' by Uguen et al.

PMID- 25957330
TI  - Chemoradiation, surgery and adjuvant chemotherapy versus induction chemotherapy
      followed by chemoradiation and surgery: long-term results of the Spanish GCR-3
      phase II randomized trial?.
AB  - BACKGROUND: The primary results of our phase II randomized trial suggested that
      compared with conventional preoperative chemoradiation (CRT), the addition of
      chemotherapy (CT) before CRT and surgery allows most patients receive their
      planned treatment with a better toxicity profile without compromising the
      pathological complete response and complete resection rates. We now report the 5
      year outcomes. PATIENTS AND METHODS: Patients with distal or middle third, T3-T4
      and/or N+ rectal adenocarcinoma selected by magnetic resonance imaging, were
      randomly assigned to arm A-preoperative CRT followed by surgery and four cycles
      of postoperative adjuvant capecitabine and oxaliplatin (CAPOX)-or arm B-four
      cycles of CAPOX followed by CRT and surgery. The following 5-year actuarial
      outcomes were assessed: the cumulative incidence of local relapse (LR) and
      distant metastases (DM), disease-free (DFS) and overall survival (OS). RESULTS: A
      total of 108 eligible patients were randomly assigned to arm A (n = 52) or arm B
      (n = 56). With a median follow-up of 69.5 months, 5-year DFS was 64% in arm A and
      62% in arm B (P = 0.85) and 5-year OS was 78% in arm A and 75% in arm B (P =
      0.64). The 5-year cumulative incidence of LR was 2% and 5% (P = 0.61) and 5-year
      cumulative incidence of DM was 21% and 23%; (P = 0.79) in arms A and B,
      respectively. CONCLUSION: Both treatment approaches yield similar outcomes. Given
      the lower acute toxicity and improved compliance with induction CT compared with
      adjuvant CT, integrating effective systemic therapy before CRT and surgery is a
      promising strategy and should be examined in phase III trials.

PMID- 25957329
TI  - Variations in genes involved in dormancy associated with outcome in patients with
      resected colorectal liver metastases.
AB  - BACKGROUND: Tumor dormancy has been described as a state of hibernation. Dormancy
      can be switched to proliferation by different pathways, which may play a critical
      role in tumor recurrence. In this study, we investigated genetic variations
      within genes involved in tumor dormancy and their association with recurrence and
      outcome in patients with colorectal liver metastases (CLM) who underwent
      neoadjuvant bevacizumab-based chemotherapy. PATIENTS AND METHODS: Genomic DNA was
      extracted from resected CLM (FFPE) from 149 patients. Single-nucleotide
      polymorphisms (SNPs) in 14 genes associated with dormancy were analyzed by direct
      Sanger DNA sequencing and evaluated for response, recurrence-free survival (RFS),
      overall survival (OS) and recurrence patterns. RESULTS: NME1 rs34214448 C>A was
      significantly associated with RFS in univariable analysis (P = 0.039) and with
      intrahepatic recurrence (P = 0.014). NOTCH3 rs1044009 T>C and CD44 rs8193 C>T
      showed a significant difference in 3-year OS rates (P = 0.004 and P = 0.042,
      respectively). With respect to radiological response, CD44 rs8193 C>T variant
      genotypes were associated with a significantly higher response rate (P = 0.033).
      Recursive partitioning analyses revealed that Dll4 rs12441495 C>G, NME1
      rs34214448 C>A and NOTCH3 rs1044009 T>C were the dominant SNPs predicting
      histological response, RFS and OS, respectively. CONCLUSION: Our data suggest
      that gene variations within genes involved in tumor dormancy pathways are
      associated with response and outcome in patients with resected CLM. These data
      may lead to new and more effective treatment strategies targeting tumor dormancy.

PMID- 25957331
TI  - Cardiorespiratory fitness and brain volume and white matter integrity: The CARDIA
      Study.
AB  - OBJECTIVE: We hypothesized that greater cardiorespiratory fitness is associated
      with lower odds of having unfavorable brain MRI findings. METHODS: We studied 565
      healthy, middle-aged, black and white men and women in the CARDIA (Coronary
      Artery Risk Development in Young Adults) Study. The fitness measure was symptom
      limited maximal treadmill test duration (Maxdur); brain MRI was measured 5 years
      later. Brain MRI measures were analyzed as means and as proportions below the
      15th percentile (above the 85th percentile for white matter abnormal tissue
      volume). RESULTS: Per 1-minute-higher Maxdur, the odds ratio for having less
      whole brain volume was 0.85 (p = 0.04) and for having low white matter integrity
      was 0.80 (p = 0.02), adjusted for age, race, sex, clinic, body mass index,
      smoking, alcohol, diet, physical activity, education, blood pressure, diabetes,
      total cholesterol, and lung function (plus intracranial volume for white matter
      integrity). No significant associations were observed between Maxdur and abnormal
      tissue volume or blood flow in white matter. Findings were similar for
      associations with continuous brain MRI measures. CONCLUSIONS: Greater physical
      fitness was associated with more brain volume and greater white matter integrity
      measured 5 years later in middle-aged adults.

PMID- 25957332
TI  - Comprehensive Opportunities for Research and Teaching Experience (CORTEX): A
      mentorship program.
AB  - OBJECTIVE: We developed a program to promote medical student interest in pursuing
      a career in neurology. This program focuses on medical student mentorship. It
      also offers opportunities in teaching and clinical research in order to provide
      students with marketable skills for an academic career in neurology. METHODS:
      Through this program, students are provided with guidance in developing a fourth
      year clerkship schedule and an application package for residency programs.
      Students are involved and mentored in clinical research. Opportunities are also
      provided for students to teach their peers, with sessions focusing on examination
      preparation. RESULTS: Since the implementation of this program in 2010, the
      number of students entering into the field of neurology from our institution
      significantly increased from 14 students between 2006 and 2010, to 30 students
      between 2011 and 2014 (p < 0.05). Medical student research productivity increased
      from 7 publications during 2006-2010, to 22 publications, 14 poster
      presentations, and a book chapter after implementation of this program in 2010 (p
      < 0.05). CONCLUSIONS: In this mentoring program, students are prepared for
      residency application and provided with research and teaching opportunities.
      Students develop a highly desirable academic skill set for residency and have
      matched at top-ranked institutions. This program has been successful in improving
      student productivity in clinical research and garnering student interest in
      neurology.

PMID- 25957333
TI  - Prevalence, knowledge, and treatment of transient ischemic attacks in China.
AB  - OBJECTIVES: To investigate the prevalence, knowledge, and treatment of TIA in a
      Chinese adult population. METHODS: We conducted a complex, multistage,
      probability sampling-designed, cross-sectional, nationwide survey of 98,658
      Chinese adults in 2010. Possible TIA cases were first identified by symptoms
      recall or self-reported history of TIA through face-to-face interviews, and the
      final diagnosis was then made by expert neurologists through phone interviews or
      record review. RESULTS: The age-standardized prevalence of TIA was 2.27%.
      Clinically, only 16.0% of the participants were diagnosed before the study. The
      prevalence of TIA was higher in women and in patients who were older, had less
      education, were current smokers, lived in rural or undeveloped areas, and had a
      history of stroke, hypertension, myocardial infarction, dyslipidemia, or
      diabetes. Based on the survey responses, approximately 3.08% of Chinese adults
      had knowledge of TIA. Among patients with TIA, only 5.02% received treatment and
      4.07% received guideline-recommended therapy. CONCLUSIONS: TIA is prevalent and
      an estimated 23.9 million people in China may have experienced a TIA. Public
      knowledge on TIA is very limited. TIA appears to be largely undiagnosed and
      untreated in China. There is an urgent need to develop strategies to improve the
      identification and appropriate management of TIA.

PMID- 25957334
TI  - Reactivation of herpesvirus under fingolimod: A case of severe herpes simplex
      encephalitis.

PMID- 25957335
TI  - Increasing student recruitment into neurology: Joining the family.

PMID- 25957336
TI  - Central paroxysmal positional nystagmus: Characteristics and possible mechanisms.
AB  - OBJECTIVE: The diagnosis of central paroxysmal positional nystagmus (CPPN) is
      challenging, and the mechanisms require further elucidation. This study aimed to
      determine the characteristics and mechanisms of CPPN. METHODS: Seventeen patients
      with CPPN were subjected to analyses of their clinical findings, MRI lesions, and
      oculographic data on spontaneous and positional nystagmus. RESULTS: The direction
      of CPPN was mostly aligned with that of the head motion during the positioning,
      and 3 types of CPPN were identified: downbeat nystagmus on straight-head hanging,
      upbeat nystagmus on uprighting, and apogeotropic nystagmus during supine head
      roll test. The direction of CPPN was aligned with the vector sum of the
      rotational axes of the semicircular canals that were normally inhibited during
      the positioning. The intensity of evoked nystagmus was at its peak initially and
      then decreased exponentially over time. The time constants (TC) of the vertical
      CPPN ranged from 3 to 8 seconds, which corresponds to the TC of the vertical
      rotational vestibulo-ocular reflex. Sixteen patients (94.1%) showed more than one
      type of CPPN. Furthermore, persistent downbeat or apogeotropic positional
      nystagmus was associated in 11 patients (64.7%). Most patients with CPPN from a
      circumscribed brain lesion showed an involvement of the cerebellar nodulus or
      uvula. CONCLUSION: CPPN may be ascribed to enhanced responses of the vestibular
      afferents due to lesions involving the nodulus and uvula. CPPN could be
      differentiated from benign paroxysmal positional nystagmus by positional
      nystagmus induced in multiple planes, temporal patterns of nystagmus intensity,
      and associated neurologic findings suggestive of central pathologies.

PMID- 25957337
TI  - The Use of Dialectical Behavior Therapy (DBT) in Music Therapy: A Sequential
      Explanatory Study.
AB  - BACKGROUND: There are published examples of how dialectical behavior therapy
      (DBT) and music therapy are effectively being used as separate therapies in the
      treatment of individuals with a variety of mental health disorders. However,
      research examining DBT-informed music therapy is limited. OBJECTIVE: The purpose
      of this study was to determine whether music therapists working in mental health
      settings are implementing components of DBT in their work, and if so, how and
      why; and if not, why not and what is their level of interest in such work.
      METHODS: We used a sequential explanatory mixed-methods research design
      implemented in two phases. Phase 1 was a quantitative survey of board-certified
      music therapists (n=260). Due to a low survey response rate (18%), and to enhance
      the validity of the findings, Phase 2, an embedded qualitative procedure in the
      form of interviews with clinicians experienced in the DBT approach, was added to
      the study. Both survey and interviews inquired about DBT training, use of DBT
      informed music therapy, music therapy experiences used to address DBT skills, and
      experiences of implementing DBT-informed music therapy. RESULTS: Respondents
      indicating they implement DBT-informed music therapy (38.3%) are using components
      and adaptations of the standard DBT protocol. Advantages of implementing DBT
      informed music therapy were identified, and more than half of the respondents who
      do not implement DBT in their music therapy practice also perceived this work as
      at least somewhat important. Disadvantages were also identified and support the
      need for further research. CONCLUSIONS: Components of DBT are used in music
      therapy and are valued, but there is a lack of empirical evidence to inform,
      refine, and guide practice.

PMID- 25957338
TI  - Self-Regulation and Infant-Directed Singing in Infants with Down Syndrome.
AB  - BACKGROUND: Infants learn how to regulate internal states and subsequent behavior
      through dyadic interactions with caregivers. During infant-directed (ID) singing,
      mothers help infants practice attentional control and arousal modulation, thus
      providing critical experience in self-regulation. Infants with Down syndrome are
      known to have attention deficits and delayed information processing as well as
      difficulty managing arousability, factors that may disrupt their efforts at self
      regulation. OBJECTIVE: The researcher explored responses to ID singing in infants
      with Down syndrome (DS) and compared them with those of typically developing (TD)
      infants. Behaviors measured included infant gaze and affect as indicators of self
      regulation. METHODS: Participants included 3- to 9-month-old infants with and
      without DS who were videotaped throughout a 2-minute face-to-face interaction
      during which their mothers sang to them any song(s) of their choosing. Infant
      behavior was then coded for percentage of time spent demonstrating a specific
      gaze or affect type. RESULTS: All infants displayed sustained gaze more than any
      other gaze type. TD infants demonstrated intermittent gaze significantly more
      often than infants with DS. Infant status had no effect on affect type, and all
      infants showed predominantly neutral affect. CONCLUSIONS: Findings suggest that
      ID singing effectively maintains infant attention for both TD infants and infants
      with DS. However, infants with DS may have difficulty shifting attention during
      ID singing as needed to adjust arousal levels and self-regulate. High levels of
      neutral affect for all infants imply that ID singing is likely to promote a calm,
      curious state, regardless of infant status.

PMID- 25957339
TI  - Smoking and (Not) Voting: The Negative Relationship Between a Health-Risk
      Behavior and Political Participation in Colorado.
AB  - INTRODUCTION: Considerable evidence suggests that cigarette smokers are an
      increasingly marginalized population, involved in fewer organizations and
      activities and with less interpersonal trust than their nonsmoking counterparts.
      However, only two previous studies, both among Swedish populations, have
      investigated smokers' attitudes toward political systems and institutions. The
      current, cross-sectional study examines smoking in relation to voting, a direct
      behavioral measure of civic and political engagement that at least partly
      reflects trust in formal political institutions. METHODS: Secondary analyses were
      conducted of interview data from 11 626 respondents in the Colorado Tobacco
      Attitudes and Behaviors Survey. Data were collected via telephone between October
      2005 and mid-April 2006 and included respondents' reported voting behavior in the
      2004 national election; the participation rate was 89.7%. Balanced multiple
      logistic regression was used to examine associations between smoking and voting
      while controlling for other covariates known to be associated with both
      variables. RESULTS: In the final model, daily smokers were less than half as
      likely as nonsmokers to report having voted in the election. CONCLUSIONS: The
      results suggest possible consonance with previous work linking smoking with
      political mistrust. Possible causal mechanisms are discussed. This study is the
      first to link a health-risk behavior with electoral participation, and provides
      initial evidence that smoking is negatively associated with political
      participation. Future research should investigate how public health might enhance
      tobacco control efforts by taking nonvoting behavior into consideration, or
      creatively combining smoking cessation interventions with voter registration and
      other civic engagement work, particularly among socioeconomically disadvantaged
      populations.

PMID- 25957341
TI  - Audible handheld Doppler ultrasound and peripheral arterial disease.

PMID- 25957340
TI  - Predictors of Cigarette Smoking Progression Among a School-Based Sample of
      Adolescents in Irbid, Jordan: A Longitudinal Study (2008-2011).
AB  - INTRODUCTION: Little evidence regarding longitudinal predictors of cigarette
      smoking progression is available from developing countries. This study aimed to
      identify gender-specific individual and social predictors of cigarette smoking
      progression among a school-based sample of adolescents in Irbid, Jordan. METHODS:
      A total of 1781 seventh graders (participation rate 95%) were enrolled and
      completed an annual self-administered questionnaire from 2008 through 2011.
      Students who reported "ever-smoking a cigarette" at baseline or in the subsequent
      follow-up but not being "heavy daily smokers" (>10 cigarettes per day) were
      eligible for this analysis (N = 669). Grouped-time survival analyses were used to
      identify predictors of cigarette smoking progression in boys and girls. RESULTS:
      Among the study sample, 38.3% of students increased the frequency and /or amount
      of cigarette smoking during the 3 years of follow-up. Among individual factors,
      the urge to smoke in the morning predicted smoking progression for boys and
      girls. The independent predictors of cigarette smoking progression were friends'
      smoking and attending public schools in boys, and siblings' smoking in girls.
      Discussing the dangers of smoking with family members was protective for girls.
      CONCLUSION: Boys and girls progressed similarly in cigarette smoking once they
      initiated the habit. Progression among girls was solely family-related, while it
      was peer-related for boys.

PMID- 25957342
TI  - Reply to letter to editor: Audible handheld Doppler ultrasound determines
      reliable and inexpensive exclusion of significant peripheral arterial disease.

PMID- 25957343
TI  - Kinetics of endothelialization of the multilayer flow modulator and single-layer
      arterial stents.
AB  - The multilayer flow modulator (MFM; Cardiatis, Isnes, Belgium) is a self
      expandable mesh of braided cobalt alloy wires, used for treatment of aortic and
      peripheral aneurysms. To further improve our understanding of this novel
      technology, the endothelialization kinetics of the MFM was investigated and
      compared with those of two marketed single-layer stents. Five porcine animal
      models were used in which a total of 19 stents were implanted in the iliac and
      carotid arteries between one and five weeks before sacrifice. All 19 stents were
      successfully delivered. For all devices, nonsignificant signs of inflammation or
      thrombosis were noted, and there was no evidence of local intolerance. The MFM
      developed a thin layer of endothelial cells earlier and was associated with less
      neointimal development than the two single-layer stents. A differing phenomenon
      of integration was also revealed and hypothesized as endothelialization from
      adhesion of circulating endothelial progenitor cells, as well as adhesion from
      the arterial wall, and also by the differences in trauma exposed to the arterial
      wall. 

PMID- 25957345
TI  - Electron microscopy study of a vascular prosthesis destructed in vivo reveals
      fractures in Dacron fibers.
AB  - The genuine destruction of a synthetic prosthesis wall, as a late complication of
      vascular surgery, is extremely rare. We report a case of a 64-year-old male who
      had his 12-year-old femoropopliteal synthetic graft explanted due to two large
      pseudoaneurysms in the middle section of the graft. Microscopic evaluation
      demonstrated the areas of focal thinning along the entire prosthesis wall, with
      "foreign body" type reaction in the adjacent connective tissue. Transmission
      electron microscopy showed longitudinal fractures of Dacron fibers interposed
      with cellular structures, suggesting that destruction must have taken place
      significantly earlier. The problems of limited graft durability and graft
      surveillance are discussed. 

PMID- 25957344
TI  - Management of isolated calf vein thrombosis in cancer patients.
AB  - The treatment of isolated calf vein thrombosis remains widely debated. This study
      highlights the characteristics of isolated calf vein thrombosis in cancer
      patients and compares to isolated calf vein thrombosis in patients without
      history of cancer. Between July 2013 and April 2014, a retrospective chart review
      of consecutive patients with isolated calf vein thrombosis was performed
      recording patient risk factors, ultrasound characteristics of the thrombus,
      treatment modalities, long-term recurrence of venous-thromboembolism, incidence
      of bleeding, and mortality. Of 131 patients with isolated calf vein thrombosis,
      53 (40.1%) had history of cancer. Isolated calf vein thrombosis occurred at an
      older age in cancer patients (66.7 vs 58.5 years, p = 0.004). The anatomical
      characteristics of isolated calf vein thrombosis on ultrasound were comparable in
      both groups. Isolated calf vein thrombosis in cancer patients was less likely to
      be treated with anticoagulation (60.4% vs 80.8%, p = 0.018). However, a trend
      towards higher incidence of bleeding after initiation of anticoagulation for
      isolated calf vein thrombosis in cancer patients (11.3% vs 6.4%, p = 0.351) was
      noted. Mortality in cancer patients was higher (37.7% vs 9.00%, p < 0.001) but
      was unrelated to isolated calf vein thrombosis or its treatment. In conclusion,
      the risks of bleeding seem to exceed the benefits of anticoagulation in
      approximately 50% of cancer patients with isolated calf vein thrombosis. The
      management of isolated calf vein thrombosis does not seem to impact the survival
      of cancer patients. 

PMID- 25957346
TI  - Understanding illness experiences of employees with common mental health
      disorders.
AB  - BACKGROUND: Common mental health disorders (CMHDs) are a leading cause of
      sickness absence. To address this, a Fit for Work Service (FFWS) was introduced
      in Greater Manchester, UK, in 2010, offering case-managed and multidisciplinary
      interventions to early-stage sickness absentees experiencing physical health
      conditions and/or associated psychosocial problems, to enable a speedy return to
      work. AIMS: To explore the illness experiences of employees who contacted or were
      referred to the Greater Manchester FFWS (GM-FFWS). METHODS: A qualitative in
      depth study, using narrative interviews with GM-FFWS service users who
      experienced mental ill-health. Interviews were recorded, transcribed and analysed
      for key themes. RESULTS: There were 21 interviews available for analysis.
      Multiple disruptive life events overwhelmed employees' capacity to cope,
      triggering mental ill-health. For some individuals, the onset of mental ill
      health was unexpected and had profound psychological effects on participants'
      sense of self and personal identity. In certain cases, previous bouts of
      emotional distress contributed to an underlying psychology of low self-esteem.
      Mobilizing resources was often a significant factor in supporting recovery. The
      illness experience led to a process of self-re-evaluation among some
      participants. CONCLUSIONS: Disruptive events at work have the potential to
      threaten an individual's sense of self. Employee's experiences of CMHDs can only
      be fully understood if there is awareness of how these experiences emerge from a
      person's biography and subsequently inform their responses to contemporary life
      events. The design of future clinical and non-clinical workplace interventions
      should take account of these biographical aspects of the illness experience.

PMID- 25957347
TI  - INPS: predicting the impact of non-synonymous variations on protein stability
      from sequence.
AB  - MOTIVATION: A tool for reliably predicting the impact of variations on protein
      stability is extremely important for both protein engineering and for
      understanding the effects of Mendelian and somatic mutations in the genome. Next
      Generation Sequencing studies are constantly increasing the number of protein
      sequences. Given the huge disproportion between protein sequences and structures,
      there is a need for tools suited to annotate the effect of mutations starting
      from protein sequence without relying on the structure. Here, we describe INPS, a
      novel approach for annotating the effect of non-synonymous mutations on the
      protein stability from its sequence. INPS is based on SVM regression and it is
      trained to predict the thermodynamic free energy change upon single-point
      variations in protein sequences. RESULTS: We show that INPS performs similarly to
      the state-of-the-art methods based on protein structure when tested in cross
      validation on a non-redundant dataset. INPS performs very well also on a newly
      generated dataset consisting of a number of variations occurring in the tumor
      suppressor protein p53. Our results suggest that INPS is a tool suited for
      computing the effect of non-synonymous polymorphisms on protein stability when
      the protein structure is not available. We also show that INPS predictions are
      complementary to those of the state-of-the-art, structure-based method mCSM. When
      the two methods are combined, the overall prediction on the p53 set scores
      significantly higher than those of the single methods. AVAILABILITY AND
      IMPLEMENTATION: The presented method is available as web server at
      http://inps.biocomp.unibo.it. CONTACT: piero.fariselli@unibo.it SUPPLEMENTARY
      INFORMATION: Supplementary Materials are available at Bioinformatics online.

PMID- 25957348
TI  - INSPEcT: a computational tool to infer mRNA synthesis, processing and degradation
      dynamics from RNA- and 4sU-seq time course experiments.
AB  - MOTIVATION: Cellular mRNA levels originate from the combined action of multiple
      regulatory processes, which can be recapitulated by the rates of pre-mRNA
      synthesis, pre-mRNA processing and mRNA degradation. Recent experimental and
      computational advances set the basis to study these intertwined levels of
      regulation. Nevertheless, software for the comprehensive quantification of RNA
      dynamics is still lacking. RESULTS: INSPEcT is an R package for the integrative
      analysis of RNA- and 4sU-seq data to study the dynamics of transcriptional
      regulation. INSPEcT provides gene-level quantification of these rates, and a
      modeling framework to identify which of these regulatory processes are most
      likely to explain the observed mRNA and pre-mRNA concentrations. Software
      performance is tested on a synthetic dataset, instrumental to guide the choice of
      the modeling parameters and the experimental design. AVAILABILITY AND
      IMPLEMENTATION: INSPEcT is submitted to Bioconductor and is currently available
      as Supplementary Additional File S1. CONTACT: mattia.pelizzola@iit.it
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 25957350
TI  - BinDNase: a discriminatory approach for transcription factor binding prediction
      using DNase I hypersensitivity data.
AB  - MOTIVATION: Transcription factors (TFs) are a class of DNA-binding proteins that
      have a central role in regulating gene expression. To reveal mechanisms of
      transcriptional regulation, a number of computational tools have been proposed
      for predicting TF-DNA interaction sites. Recent studies have shown that genome
      wide sequencing data on open chromatin sites from a DNase I hypersensitivity
      experiments (DNase-seq) has a great potential to map putative binding sites of
      all transcription factors in a single experiment. Thus, computational methods for
      analysing DNase-seq to accurately map TF-DNA interaction sites are highly needed.
      RESULTS: Here, we introduce a novel discriminative algorithm, BinDNase, for
      predicting TF-DNA interaction sites using DNase-seq data. BinDNase implements an
      efficient method for selecting and extracting informative features from DNase I
      signal for each TF, either at single nucleotide resolution or for larger regions.
      The method is applied to 57 transcription factors in cell line K562 and 31
      transcription factors in cell line HepG2 using data from the ENCODE project.
      First, we show that BinDNase compares favourably to other supervised and
      unsupervised methods developed for TF-DNA interaction prediction using DNase-seq
      data. We demonstrate the importance to model each TF with a separate prediction
      model, reflecting TF-specific DNA accessibility around the TF-DNA interaction
      site. We also show that a highly standardised DNase-seq data (pre)processing is a
      requisite for accurate TF binding predictions and that sequencing depth has on
      average only a moderate effect on prediction accuracy. Finally, BinDNase's
      binding predictions generalise to other cell types, thus making BinDNase a
      versatile tool for accurate TF binding prediction. AVAILABILITY AND
      IMPLEMENTATION: R implementation of the algorithm is available in:
      http://research.ics.aalto.fi/csb/software/bindnase/. CONTACT:
      juhani.kahara@aalto.fi SUPPLEMENTARY INFORMATION: Supplemental data are available
      at Bioinformatics online.

PMID- 25957349
TI  - Tax4Fun: predicting functional profiles from metagenomic 16S rRNA data.
AB  - MOTIVATION: The characterization of phylogenetic and functional diversity is a
      key element in the analysis of microbial communities. Amplicon-based sequencing
      of marker genes, such as 16S rRNA, is a powerful tool for assessing and comparing
      the structure of microbial communities at a high phylogenetic resolution. Because
      16S rRNA sequencing is more cost-effective than whole metagenome shotgun
      sequencing, marker gene analysis is frequently used for broad studies that
      involve a large number of different samples. However, in comparison to shotgun
      sequencing approaches, insights into the functional capabilities of the community
      get lost when restricting the analysis to taxonomic assignment of 16S rRNA data.
      RESULTS: Tax4Fun is a software package that predicts the functional capabilities
      of microbial communities based on 16S rRNA datasets. We evaluated Tax4Fun on a
      range of paired metagenome/16S rRNA datasets to assess its performance. Our
      results indicate that Tax4Fun provides a good approximation to functional
      profiles obtained from metagenomic shotgun sequencing approaches. AVAILABILITY
      AND IMPLEMENTATION: Tax4Fun is an open-source R package and applicable to output
      as obtained from the SILVAngs web server or the application of QIIME with a SILVA
      database extension. Tax4Fun is freely available for download at
      http://tax4fun.gobics.de/. CONTACT: kasshau@gwdg.de SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 25957351
TI  - Using combined evidence from replicates to evaluate ChIP-seq peaks.
AB  - MOTIVATION: Chromatin Immunoprecipitation followed by sequencing (ChIP-seq)
      detects genome-wide DNA-protein interactions and chromatin modifications,
      returning enriched regions (ERs), usually associated with a significance score.
      Moderately significant interactions can correspond to true, weak interactions, or
      to false positives; replicates of a ChIP-seq experiment can provide co-localised
      evidence to decide between the two cases. We designed a general methodological
      framework to rigorously combine the evidence of ERs in ChIP-seq replicates, with
      the option to set a significance threshold on the repeated evidence and a minimum
      number of samples bearing this evidence. RESULTS: We applied our method to Myc
      transcription factor ChIP-seq datasets in K562 cells available in the ENCODE
      project. Using replicates, we could extend up to 3 times the ER number with
      respect to single-sample analysis with equivalent significance threshold. We
      validated the 'rescued' ERs by checking for the overlap with open chromatin
      regions and for the enrichment of the motif that Myc binds with strongest
      affinity; we compared our results with alternative methods (IDR and jMOSAiCS),
      obtaining more validated peaks than the former and less peaks than latter, but
      with a better validation. AVAILABILITY AND IMPLEMENTATION: An implementation of
      the proposed method and its source code under GPLv3 license are freely available
      at http://www.bioinformatics.deib.polimi.it/MSPC/ and http://mspc.codeplex.com/,
      respectively. CONTACT: marco.morelli@iit.it SUPPLEMENTARY INFORMATION:
      Supplementary Material are available at Bioinformatics online.

PMID- 25957352
TI  - Interactive analysis of large cancer copy number studies with Copy Number
      Explorer.
AB  - Copy number abnormalities (CNAs) such as somatically-acquired chromosomal
      deletions and duplications drive the development of cancer. As individual tumor
      genomes can contain tens or even hundreds of large and/or focal CNAs, a major
      difficulty is differentiating between important, recurrent pathogenic changes and
      benign changes unrelated to the subject's phenotype. Here we present Copy Number
      Explorer, an interactive tool for mining large copy number datasets. Copy Number
      Explorer facilitates rapid visual and statistical identification of recurrent
      regions of gain or loss, identifies the genes most likely to drive CNA formation
      using the cghMCR method and identifies recurrently broken genes that may be
      disrupted or fused. The software also allows users to identify recurrent CNA
      regions that may be associated with differential survival. AVAILABILITY AND
      IMPLEMENTATION: Copy Number Explorer is available under the GNU public license
      (GPL-3). Source code is available at:
      https://sourceforge.net/projects/copynumberexplorer/ CONTACT:
      scott.newman@emory.edu.

PMID- 25957353
TI  - Gener: a minimal programming module for chemical controllers based on DNA strand
      displacement.
AB  - : Gener is a development module for programming chemical controllers based on DNA
      strand displacement. Gener is developed with the aim of providing a simple
      interface that minimizes the opportunities for programming errors: Gener allows
      the user to test the computations of the DNA programs based on a simple two
      domain strand displacement algebra, the minimal available so far. The tool allows
      the user to perform stepwise computations with respect to the rules of the
      algebra as well as exhaustive search of the computation space with different
      options for exploration and visualization. Gener can be used in combination with
      existing tools, and in particular, its programs can be exported to Microsoft
      Research's DSD tool as well as to LaTeX. AVAILABILITY AND IMPLEMENTATION: Gener
      is available for download at the Cosbi website at
      http://www.cosbi.eu/research/prototypes/gener as a windows executable that can be
      run on Mac OS X and Linux by using Mono. CONTACT: ozan@cosbi.eu.

PMID- 25957354
TI  - MemGen: a general web server for the setup of lipid membrane simulation systems.
AB  - MOTIVATION: Molecular dynamics simulations provide atomic insight into the
      physicochemical characteristics of lipid membranes and hence, a wide range of
      force field families capable of modelling various lipid types have been developed
      in recent years. To model membranes in a biologically realistic lipid
      composition, simulation systems containing multiple different lipids must be
      assembled. RESULTS: We present a new web service called MemGen that is capable of
      setting up simulation systems of heterogenous lipid membranes. MemGen is not
      restricted to certain lipid force fields or lipid types, but instead builds
      membranes from uploaded structure files which may contain any kind of amphiphilic
      molecule. MemGen works with any all-atom or united-atom lipid representation.
      AVAILABILITY AND IMPLEMENTATION: MemGen is freely available without registration
      at http://memgen.uni-goettingen.de. CONTACT: jhub@gwdg.de SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 25957356
TI  - Sarcocystis fayeri-Induced Granulomatous and Eosinophilic Myositis in 2 Related
      Horses.
AB  - This report describes 2 genetically related paint mares, case Nos. 1 and 2,
      presented to the Oklahoma State University Boren Veterinary Medical Teaching
      Hospital for chronic weight loss and abnormal gait, respectively. Notable
      findings in both cases included marked persistent eosinophilia and multiple
      intramuscular lateral thoracic masses. Histologic examination of masses revealed
      eosinophilic, centrally necrotic granulomas and marked eosinophilic myositis.
      Granulomas in case No. 1 also contained intralesional Sarcocystis sp material,
      and adjacent muscle fibers contained intact protozoal cysts. Case No. 1 developed
      severe refractory muscle pain and recurrent esophageal dysphagia. At necropsy,
      disseminated, grossly visible granulomas were present throughout all examined
      striated muscles. Nested polymerase chain reaction of the 18S rRNA gene revealed
      >99% homology with Sarcocystis fayeri. Sarcocystis spp are apicomplexan protozoa
      that infect striated muscle of many omnivorous species, typically without
      inciting clinical disease. Sarcocystosis should be considered a rare cause of
      granulomatous eosinophilic myositis and choke in horses. 

PMID- 25957355
TI  - High and Low Affinity Urea Root Uptake: Involvement of NIP5;1.
AB  - Urea is the most widespread nitrogen (N) fertilizer worldwide and is rapidly
      degraded in soil to ammonium by urease. Ammonium is either taken up by plant
      roots or is further processed to nitrate by soil microorganisms. However, urea
      can be taken up by roots and is further degraded to ammonium by plant urease for
      assimilation. When urea is supplied under sterile conditions, it acts as a poor N
      source for seedlings or adult Arabidopsis thaliana plants. Here, the gene
      expression of young seedlings exposed to urea and ammonium nitrate nutrition was
      compared. Several primary metabolism and transport genes, including those for
      nitrate and urea, were differentially expressed in seedlings. However, urease and
      most major intrinsic proteins were not differentially expressed, with the
      exception of NIP6;1, a urea-permeable channel, which was repressed. Furthermore,
      little overlap with the gene expression with ammonium as the sole N source was
      observed, confirming that pure urea nutrition is not associated with the ammonium
      toxicity syndrome in seedlings. The direct root uptake of urea was increased
      under boron deficiency, in both the high and low affinity range. This activity
      was entirely mediated by the NIP5;1 channel, which was confirmed to transport
      urea when expressed in oocytes. The uptake of urea in the high and low affinity
      range was also determined for maize and wheat roots. The urea uptake by maize
      roots was only about half that of wheat, but was not stimulated by boron
      deficiency or N deficiency in either species. This analysis identifies novel
      components of the urea uptake systems in plants, which may become agronomically
      relevant to urea uptake and utilization, as stabilized urea fertilizers become
      increasingly popular. 

PMID- 25957357
TI  - Benign and Malignant Proliferative Fibro-osseous and Osseous Lesions of the Oral
      Cavity of Dogs.
AB  - Ossifying fibroma (OF) and fibrous dysplasia (FD) are benign, intraosseous,
      proliferative fibro-osseous lesions (PFOLs) characterized by replacement of
      normal bone by a fibrous matrix with various degrees of mineralization and
      ossification. Osteomas are benign tumors composed of mature, well-differentiated
      bone. Clinical, imaging, and histologic features of 15 initially diagnosed benign
      PFOLs and osteomas of the canine oral cavity were evaluated. Final diagnoses
      after reevaluation were as follows: OF (3 cases), FD (4 cases), low-grade
      osteosarcoma (LG-OSA) (3 cases), and osteoma (5 cases). Histology alone often did
      not result in a definitive diagnosis for PFOL. OF appeared as a well
      circumscribed, radiopaque mass with some degree of bone lysis on imaging. Most
      lesions of FD showed soft tissue opacity with bone lysis and ill-defined margins.
      Low-grade OSA appeared as a lytic lesion with a mixed opacity and ill-defined
      margins. Osteomas were characterized by a mineralized, expansile, well
      circumscribed lesion. Although histologic features of PFOLs were typically bland,
      the lesions diagnosed as LG-OSA had some features of malignancy (eg, bone
      invasion or a higher mitotic index). Treatment varied widely. Of the 10 dogs with
      benign PFOL or osteoma with known outcome (10/12), 9 showed either complete
      response (6/10) or stable disease (3/10) after treatment. Of the 2 dogs with LG
      OSA with known outcome, 1 showed complete response after curative intent surgery,
      but 1 patient had recurrence after partial maxillectomy. Definitive diagnosis of
      mandibular/maxillary PFOL is challenging via histopathologic examination alone,
      and accurate diagnosis is best achieved through assimilation of clinical,
      imaging, and histopathologic features. 

PMID- 25957358
TI  - World Small Animal Veterinary Association Renal Pathology Initiative:
      Classification of Glomerular Diseases in Dogs.
AB  - Evaluation of canine renal biopsy tissue has generally relied on light
      microscopic (LM) evaluation of hematoxylin and eosin-stained sections ranging in
      thickness from 3 to 5 um. Advanced modalities, such as transmission electron
      microscopy (TEM) and immunofluorescence (IF), have been used sporadically or
      retrospectively. Diagnostic algorithms of glomerular diseases have been
      extrapolated from the World Health Organization classification scheme for human
      glomerular disease. With the recent establishment of 2 veterinary nephropathology
      services that evaluate 3-um sections with a panel of histochemical stains and
      routinely perform TEM and IF, a standardized objective species-specific approach
      for the diagnosis of canine glomerular disease was needed. Eight veterinary
      pathologists evaluated 114 parameters (lesions) in renal biopsy specimens from 89
      dogs. Hierarchical cluster analysis of the data revealed 2 large categories of
      glomerular disease based on the presence or absence of immune complex deposition:
      The immune complex-mediated glomerulonephritis (ICGN) category included cases
      with histologic lesions of membranoproliferative or membranous patterns. The
      second category included control dogs and dogs with non-ICGN (glomerular
      amyloidosis or focal segmental glomerulosclerosis). Cluster analysis performed on
      only the LM parameters led to misdiagnosis of 22 of the 89 cases-that is, ICGN
      cases moved to the non-ICGN branch of the dendrogram or vice versa, thereby
      emphasizing the importance of advanced diagnostic modalities in the evaluation of
      canine glomerular disease. Salient LM, TEM, and IF features for each pattern of
      disease were identified, and a preliminary investigation of related
      clinicopathologic data was performed. 

PMID- 25957360
TI  - Content usage and the most frequently read articles of 2014.

PMID- 25957359
TI  - Electronic health record innovations for healthier patients and happier doctors.
AB  - This special issue explores a range of health information technology (HIT) issues
      that can help primary care practices and patients. Findings address the design of
      HIT systems, primarily electronic health records (EHRs), the utility of various
      functionalities, and implementation strategies that ensure the greatest value.
      The articles also remind us that, while HIT can support the delivery of care, it
      is not a panacea. To be effective, functionality needs to be relevant and timely
      for both the clinician and patient. Prompts and better documentation can improve
      care, and "prompt fatigue" is not inevitable. Information presented within EHRs
      needs to be actionable. There is an ongoing tension between information overload
      and the right-and helpful-information. Even the order of presentation of
      information can make a difference in the outcome. Whether supported by HIT or
      not, basic tenants of care, such as including the whole care team in trainings,
      communicating with other providers, and engaging patients, remain essential. The
      studies in this issue will prove useful for informatics developers, practices and
      health systems making HIT decisions, and care teams refining HIT to support the
      needs of their patients. 

PMID- 25957361
TI  - Health information technology needs help from primary care researchers.
AB  - While health information technology (HIT) efforts are beginning to yield
      measurable clinical benefits, more is needed to meet the needs of patients and
      clinicians. Primary care researchers are uniquely positioned to inform the
      evidence-based design and use of technology. Research strategies to ensure
      success include engaging patient and clinician stakeholders, working with
      existing practice-based research networks, and using established methods from
      other fields such as human factors engineering and implementation science.
      Policies are needed to help support primary care researchers in evaluating and
      implementing HIT into everyday practice, including expanded research funding,
      strengthened partnerships with vendors, open access to information systems, and
      support for the Primary Care Extension Program. Through these efforts, the goal
      of improved outcomes through HIT can be achieved. 

PMID- 25957362
TI  - Family physician geriatricians do mostly geriatric care: is this a problem for
      our specialty?

PMID- 25957363
TI  - Reported practice patterns among family physicians with a geriatrics certificate
      of added qualifications.
AB  - Practice patterns of family physicians with additional certification are unknown
      but are important to workforce planners and policymakers, who may presume that
      all family physicians provide primary care to patients of all ages. We found that
      a majority of family medicine geriatricians self-report practicing primarily
      geriatric medicine. 

PMID- 25957364
TI  - Physician Information Needs and Electronic Health Records (EHRs): Time to
      Reengineer the Clinic Note.
AB  - BACKGROUND: Primary care physicians face cognitive overload daily, perhaps
      exacerbated by the form of electronic health record documentation. We examined
      physician information needs to prepare for clinic visits, focusing on past clinic
      progress notes. METHODS: This study used cognitive task analysis with 16 primary
      care physicians in the scenario of preparing for office visits. Physicians
      reviewed simulated acute and chronic care visit notes. We collected field notes
      and document highlighting and review, and we audio-recorded cognitive interview
      while on task, with subsequent thematic qualitative analysis. Member checks
      included the presentation of findings to the interviewed physicians and their
      faculty peers. RESULTS: The Assessment and Plan section was most important and
      usually reviewed first. The History of the Present Illness section could provide
      supporting information, especially if in narrative form. Physicians expressed
      frustration with the Review of Systems section, lamenting that the forces driving
      note construction did not match their information needs. Repetition of
      information contained in other parts of the chart (eg, medication lists) was
      identified as a source of note clutter. A workflow that included a patient
      summary dashboard made some elements of past notes redundant and therefore a
      source of clutter. CONCLUSIONS: Current ambulatory progress notes present more
      information to the physician than necessary and in an antiquated format. It is
      time to reengineer the clinic progress note to match the workflow and information
      needs of its primary consumer.

PMID- 25957365
TI  - Impact of an Electronic Health Record (EHR) Reminder on Human Papillomavirus
      (HPV) Vaccine Initiation and Timely Completion.
AB  - BACKGROUND: The initiation and timely completion of the human papillomavirus
      (HPV) vaccine in young women is critical. We compared the initiation and
      completion of the HPV vaccine among women in 2 community-based networks with
      electronic health records: 1 with a prompt and reminder system (prompted cohort)
      and 1 without (unprompted cohort). METHODS: Female patients aged 9 to 26 years
      seen between March 1, 2007, and January 25, 2010, were used as the retrospective
      cohort. Patient demographics and vaccination dates were extracted from the
      electronic health records. RESULTS: Patients eligible for the vaccine included
      6019 from the prompted cohort and 9096 from the unprompted cohort. Mean age at
      initiation was 17.3 years in the prompted cohort and 18.1 years in the unprompted
      cohort. Significantly more (P < .001) patients initiated the vaccine in the
      prompted cohort (34.9%) compared with the unprompted cohort (21.5%). African
      Americans aged 9 to 18 years with >=3 visits during the observation period were
      significantly more likely to initiate in the prompted cohort (P < .001). The
      prompted cohort was significantly more likely (P < .001) to complete the vaccine
      series in a timely manner compared with the unprompted cohort. CONCLUSION: More
      patients aged 9 to 26 years initiated and achieved timely completion of the HPV
      vaccine series in clinics using an electronic health record system with prompts
      compared with clinics without prompts.

PMID- 25957366
TI  - Prompting Primary Care Providers about Increased Patient Risk As a Result of
      Family History: Does It Work?
AB  - BACKGROUND: Electronic health records have the potential to facilitate family
      history use by primary care physicians (PCPs) to provide personalized care. The
      objective of this study was to determine whether automated, at-the-visit tailored
      prompts about family history risk change PCP behavior. METHODS: Automated,
      tailored prompts highlighting familial risk for heart disease, stroke, diabetes,
      and breast, colorectal, or ovarian cancer were implemented during 2011 to 2012.
      Medical records of a cohort of community-based primary care patients, aged 35 to
      65 years, who previously participated in our Family Healthware study and had a
      moderate or strong familial risk for any of the 6 diseases were subsequently
      reviewed. The main outcome measures were PCP response to the prompts, adding
      family history risk to problem summary lists, and patient screening status for
      each disease. RESULTS: The 492 eligible patients had 847 visits during the study
      period; 152 visits had no documentation of response to a family history prompt.
      Of the remaining 695 visits, physician responses were reviewed family history (n
      = 372, 53.5%), discussed family history (n = 159, 22.9%), not addressed (n = 155,
      22.3%), and reviewed family history and ordered tests/referrals (n = 5, 0.7%).
      There was no significant change in problem summary list documentation of risk
      status or screening interventions for any of the 6 diseases. CONCLUSIONS: No
      change occurred upon instituting simple, at-the-visit family history prompts
      geared to improve PCPs' ability to identify patients at high risk for 6 common
      conditions. The results are both surprising and disappointing. Further studies
      should examine physicians' perception of the utility of prompts for family
      history risk.

PMID- 25957367
TI  - Point-of-Care Estimated Radiation Exposure and Imaging Guidelines Can Reduce
      Pediatric Radiation Burden.
AB  - INTRODUCTION: The steady increase in the use of computed tomography (CT) has
      particular concerns for children. Family physicians must often select pediatric
      imaging without any decision support. We hypothesized that point-of-care decision
      support would lead to the selection of imaging that lowered radiation exposure
      and improved guideline congruence. METHODS: Our double-blind, randomized
      simulation included family physicians in the Military Health System. Participants
      initially reviewed a pediatric hematuria scenario and selected imaging without
      decision support. Participants were subsequently randomized to either receive
      imaging-appropriateness guidelines and then estimated radiation exposure
      information or receive estimated radiation information then guidelines; imaging
      selections were required after each step. The primary outcome was the selected
      imaging modality with point-of-care decision support. RESULTS: The first arm
      increased CT ordering after viewing the guidelines (P = .008) but then decreased
      it after reviewing radiation exposure information (P = .007). In the second arm
      radiation information decreased CT and plain film use (P = not significant), with
      a subsequent increase in ultrasound and CT after the guideline presentation (P =
      .05). CONCLUSIONS: Decision support during a simulated pediatric scenario helped
      family physicians select imaging that lowered radiation exposure and was aligned
      with current guidelines, especially when presented with radiation information
      after guideline review. This information could help inform electronic medical
      record design.

PMID- 25957368
TI  - Clinical reminders designed and implemented using cognitive and organizational
      science principles decrease reminder fatigue.
AB  - BACKGROUND: Response rates to point-of-care clinical reminders typically decrease
      over time. We hypothesized that this "reminder fatigue" could be prevented by (1)
      applying sound human factors engineering and cognitive science principles in
      designing the reminder system, and (2) implementing the reminders with rigorous
      attention to organizational science principles. METHODS: This was a retrospective
      cohort enumeration from January 1, 2006, through July 31, 2012, in a set of 5
      academically affiliated family medicine practices. We modeled the odds ratio of
      clinician action in response to a reminder according to the number of reminders
      issued during the encounter, the number of problems on the patient's problem
      list, patient age, and time (number of months since launch) using logistic
      regression with clustering by encounter. RESULTS: There were issued 988,149
      reminders at 453,537 encounters during the sampling frame. Action was taken in
      response to 60.1% of reminders, and discussion or consideration was documented in
      another 26.8%. The odds ratios for action in response to reminders over time, by
      number of prompts during the encounter, and by number of problems were 1.01,
      1.18, and 1.02, respectively. Key design features included issuing reminders only
      when a service was due, allowing clinicians to attend to reminders when doing so
      fit their workflow (vs forcing attention at a specific time), keeping reminders
      very short and simple (action item only, no explicative material), and a team
      meeting and buy-in process before each new reminder was implemented. CONCLUSIONS:
      Reminder fatigue over time, with increasing numbers of reminders and with
      increasing complexity of patients, is not inevitable. A reminder system designed
      and implemented in accordance with the principles of cognitive science and human
      factors engineering can prevent reminder fatigue.

PMID- 25957369
TI  - Learning from primary care meaningful use exemplars.
AB  - BACKGROUND: Submission of clinical quality measures (CQMs) data are 1 of 3 major
      requirements for providers to receive meaningful use (MU) incentive payments
      under the 2009 Health Information Technology for Economic and Clinical Health
      (HITECH) Act. Some argue that CQMs are the most important component of MU.
      Developing an evidence base for how practices can successfully use electronic
      health records (EHRs) to achieve improvement in CQMs is essential and may benefit
      from the study of exemplars who have successfully implemented EHRs and
      demonstrated high performance on CQMs. METHODS: Conducted in PPRNet, a national
      primary care practice-based research network, this study used a multimethod
      approach combining an EHR-based CQM performance assessment, a provider survey,
      and focus groups among high CQM performers. Practices whose providers had
      attested for stage 1 MU were eligible for the study. Performance on 21 CQMs
      included in the 2014 MU CQM set and a summary measure was assessed as of October
      1, 2013, through an automated data extract and standard analytic procedures. A
      web-based provider survey, conducted in November to December 2013, assessed
      provider agreement, staff education, use of EHR reminders, standing orders, and
      EHR-based patient education related to the 21 CQMs. The survey also had more
      general questions about the practices' use of EHR functionality and quality
      improvement (QI) strategies. Statistical analyses using general linear mixed
      models assessed the associations between responses to the survey and CQM
      performance, adjusted for several practice covariates. Three focus groups, held
      in early 2014, provided an opportunity for clinicians to provide their
      perspectives on the validity of the statistical analyses and to provide context
      specific examples from their practice that supported their assessment. RESULTS:
      Seventy-one practices completed the study, and 319 (92.1%) of their providers
      completed the survey. There was wide variability in performance on the 21 CQMs
      among the practices. Mean performance ranged from 89.8% for tobacco use screening
      and counseling to 12.9% for chlamydia screening. In bivariate analyses, more
      positive associations were found between CQM performance and staff education, use
      of standing orders, and EHR reminders than for provider agreement or EHR-based
      patient education. In multivariate analyses, EHR reminders were most frequently
      associated with individual CQM performance; several EHR, practice QI, and
      administrative variables were associated with the summary quality measure.
      CONCLUSIONS: Purposeful use of EHR functionality coupled with staff education in
      a milieu where QI is valued and supported is associated with higher performance
      on CQM.

PMID- 25957370
TI  - The use of medical scribes in health care settings: a systematic review and
      future directions.
AB  - BACKGROUND: Electronic health records (EHRs) hold promise to improve
      productivity, quality, and outcomes; however, using EHRs can be cumbersome,
      disruptive to workflow, and off-putting to patients and clinicians. One proposed
      solution to this problem is the use of medical scribes. The purpose of this
      systematic review is to summarize the literature investigating the effect of
      medical scribes on health care productivity, quality, and outcomes. Implications
      for future research are discussed. METHODS: A keyword search of the Cochrane
      Library, OvidSP Medline database, and Embase database from January 2000 through
      September 2014 was performed using the terms scribe or scribes in the title or
      abstract. To ensure no potentially eligible articles were missed, a second search
      was done using Google Scholar. English-language, peer-reviewed studies assessing
      the effect of medical scribes on health care productivity, quality, and outcomes
      were retained. Identified studies were assessed and the findings reported.
      RESULTS: Five studies were identified. Three studies assessed scribe use in an
      emergency department, 1 in a cardiology clinic, and 1 in a urology clinic. Two of
      3 studies reported scribes had no effect on patient satisfaction; 2 of 2 reported
      improved clinician satisfaction; 2 of 3 reported an increase in the number of
      patients; 2 of 2 reported an increase in the number of relative value units per
      hour; 1 of 1 reported increased revenue; 3 of 4 reported improved time-related
      efficiencies; and 1 of 1 reported improved patient-clinician interactions.
      CONCLUSIONS: Available evidence suggests medical scribes may improve clinician
      satisfaction, productivity, time-related efficiencies, revenue, and patient
      clinician interactions. Because the number of studies is small, and because each
      study suffered important limitations, confidence in the reliability of the
      evidence is significantly constrained. Given the nascent state of the science,
      methodologically rigorous and sufficiently powered studies are greatly needed.

PMID- 25957372
TI  - Impact of and Satisfaction with a New eConsult Service: A Mixed Methods Study of
      Primary Care Providers.
AB  - OBJECTIVES: We have improved access to specialist care and decreased wait times
      in our region through the development and implementation of the Champlain BASE
      (Building Access to Specialists through eConsultation) service. This secure, web
      based tool allows primary care providers (PCPs) quick access to specialist advice
      for their patients and often helps to avoid the need for a face-to-face referral.
      Our successful implementation of eConsult in our region provides a unique
      opportunity to examine PCPs' satisfaction and overall perspective on using the
      service. METHODS: Following the closure of each case, PCPs completed a short
      survey with multiple-choice and open-ended questions regarding the eConsult. All
      eConsults submitted between April 15, 2011, and December 31, 2013, were analyzed.
      We calculated satisfaction scores from the survey and conducted a constant
      comparison thematic analysis on those cases where the PCP elected to leave a text
      response. RESULTS: We analyzed 2,052 eConsults completed during the study period.
      In 91% and 93% of eConsults, PCPs reported a high value for their patients and
      themselves, respectively. In 554 eConsults, PCPs elected to leave a written
      response. Three major themes emerged: PCP appreciation of the eConsult service,
      perceived benefits for the quality of patient care, and attitudes towards using a
      new health technology. High satisfaction was expressed with quick response times,
      helpfulness of responses, and reassurance reported. Most PCPs felt eConsult had a
      positive impact on patient care by also providing reassurance to patients,
      reducing burden of time and travel, and offering educational opportunities to
      PCPs applicable to future cases. CONCLUSION: PCPs showed a high level of
      satisfaction with eConsult's quick turnaround time and quality of specialist
      advice. Our results illustrate the advantages of using asynchronous virtual
      platforms to increase access to specialty care from a PCP perspective.

PMID- 25957371
TI  - Planning for Action: The Impact of an Asthma Action Plan Decision Support Tool
      Integrated into an Electronic Health Record (EHR) at a Large Health Care System.
AB  - INTRODUCTION: Asthma is a chronic airway disease that can be difficult to manage,
      resulting in poor outcomes and high costs. Asthma action plans assist patients
      with self-management, but provider compliance with this recommendation is limited
      in part because of guideline complexity. This project aimed to embed an
      electronic asthma action plan decision support tool (eAAP) into the medical
      record to streamline evidence-based guidelines for providers at the point of
      care, create individualized patient handouts, and evaluate effects on disease
      outcomes. METHODS: eAAP development occurred in 4 phases: web-based prototype
      creation, multidisciplinary team engagement, pilot, and system-wide
      dissemination. Medical record and hospital billing data compared frequencies of
      asthma exacerbations before and after eAAP receipt with matched controls.
      RESULTS: Between December 2012 and September 2014, 5174 patients with asthma
      (~10%) received eAAPs. Results showed an association between eAAP receipt and
      significant reductions in pediatric asthma exacerbations, including 33% lower
      odds of requiring oral steroids (P < .001), compared with controls. Equivalent
      adult measures were not statistically significant. CONCLUSIONS: This study
      supports existing evidence that patient self-management plays an important role
      in reducing asthma exacerbations. We show the feasibility of leveraging
      technology to provide guideline-based decision support through an eAAP,
      addressing known challenges of implementation into routine practice.

PMID- 25957373
TI  - Interspecialty communication supported by health information technology
      associated with lower hospitalization rates for ambulatory care-sensitive
      conditions.
AB  - BACKGROUND: Practice tools such as health information technology (HIT) have the
      potential to support care processes, such as communication between health care
      providers, and influence care for "ambulatory care-sensitive conditions" (ACSCs).
      ACSCs are conditions for which good outpatient care can potentially prevent the
      need for hospitalization. To date, associations between such primary care
      practice capabilities and hospitalizations for ambulatory care-sensitive
      conditions have been primarily limited to smaller, local studies or unique
      delivery systems rather than nationally representative studies of primary care
      physicians in the United States. METHODS: We analyzed a nationally representative
      sample of 1,819 primary care physicians who responded to the Center for Studying
      Health System Change's Physician Survey. We linked 3 years of Medicare claims
      (2007 to 2009) with these primary care physician survey respondents. This linkage
      resulted in the identification of 123,760 beneficiaries with one or more of 4
      ambulatory care-sensitive chronic conditions (diabetes, chronic obstructive
      pulmonary disease, asthma, and congestive heart failure) for whom these
      physicians served as the usual provider. Key independent variables of interest
      were physicians' practice capabilities, including communication with specialists,
      use of care managers, participation in quality and performance measurement, use
      of patient registries, and HIT use. The dependent variable was a summary measure
      of ambulatory care-sensitive hospitalizations for one or more of these 4
      conditions. RESULTS: Higher provider-reported levels of communication between
      primary care and specialist physicians were associated with lower rates of
      potentially avoidable hospitalizations. While there was no significant main
      effect between HIT use and ACSC hospitalizations, the associations between
      interspecialty communication and ACSC hospitalizations were magnified in the
      presence of higher HIT use. For example, patients in practices with both the
      highest level of interspecialty communication and the highest level of HIT use
      had lower odds of ambulatory care-sensitive hospitalizations than did those in
      practices with lower interspecialty communication and high HIT use (adjusted odds
      ratio, 0.70; 95% confidence limits, 0.59, 0.82). CONCLUSIONS: Greater primary
      care and specialist communication is associated with reduced hospitalizations for
      ambulatory care-sensitive conditions. This effect was magnified in the presence
      of higher provider-reported HIT use, suggesting that coordination of care with
      support from HIT is important in the treatment of ambulatory care-sensitive
      conditions.

PMID- 25957374
TI  - Prioritization of patients for comprehensive medication review by a clinical
      pharmacist in family medicine.
AB  - BACKGROUND: This pilot study describes and evaluates the clinical pharmacy
      priority (CP2) score. We hypothesize that patients with high CP2 scores are more
      likely to receive a medication recommendation after comprehensive medication
      review (CMR) than patients with lower scores. Prioritization of patients for CMR
      by a clinical pharmacist in family medicine could enhance the provision of
      interprofessional care within the patient-centered medical home. METHODS: The CP2
      score was developed collaboratively by the research team and is derived from 11
      patient-specific factors extracted from the electronic health record. To evaluate
      the utility of the score, CMR was performed prospectively by a clinical
      pharmacist for patients with appointments between October 1 and December 31,
      2012, at 2 University of Colorado family medicine clinics. RESULTS: CMR was
      performed for 1107 patient appointments. Of these, 101 were identified as having
      received a medication recommendation from the clinical pharmacist. For patients
      with a CP2 score of 0 to 2, 2 of 588 charts (0.3%) reviewed received a
      recommendation (level 1). The proportion increased to 37 of 358 (10.3%) for
      scores of 3 to 7 (level 2), 40 of 119 (33.6%) for scores of 8 to 10 (level 3),
      and 22 of 42 (52.4%) for scores of >=11 (level 4). Compared with CP2 scores in
      level 1, patient appointments were more likely to receive a medication
      recommendation after CMR in level 2 (relative risk [RR], 30.4; 95% confidence
      interval [CI], 7.4-125.3), in level 3 (RR, 98.8; 95% CI, 24.2-403.3), and in
      level 4 (RR, 154; 95% CI, 37.5-632.8). CONCLUSIONS: Patients with higher CP2
      scores were more likely to receive a medication recommendation after CMR by a
      clinical pharmacist than patients with lower scores. The CP2 score could be used
      by clinical pharmacists in family medicine to enhance the efficient and effective
      delivery of interprofessional care.

PMID- 25957375
TI  - Internal jugular vein septic thrombophlebitis (lemierre syndrome) as a
      complication of pharyngitis.
AB  - Sore throat is a common presenting complaint in the outpatient setting. Most
      cases are nonbacterial in origin, but those that are bacterial are usually the
      result of group A beta-hemolytic streptococcus. Guidelines exist to help
      physicians decide whether to treat with an antibiotic. Lemierre syndrome is a
      dangerous potential sequela of pharyngitis that results in septic
      thrombophlebitis of the internal jugular (IJ) vein. A high index of suspicion is
      needed to consider this diagnosis in the workup of pharyngitis and should be
      aggressively treated once identified. Consideration should be given to completing
      blood cultures and neck imaging because of clinical suspicion. The case study
      discussed here illustrates the presentation, evaluation, and treatment of
      Lemierre syndrome. 

PMID- 25957376
TI  - Prevalence of guttae in the graft following corneal transplantation.
AB  - AIM: To evaluate the prevalence of guttae in donor grafts following corneal
      transplantation and to examine the possible effect of guttae on postoperative
      results. METHODS: Retrospective cohort study. We reviewed the medical records of
      all keratoplasties performed at the Villa Serena-Villa Igea private hospitals
      (Forli, Italy) between January 2005 and July 2014. Endothelial specular
      microscopy images were examined to identify the presence of guttae. Donor's age,
      patient's age, indication for surgery, surgical procedure, postoperative visual
      acuity, and endothelial cell density were also noted. RESULTS: A total of 11 068
      postoperative specular microscopy pictures were available for 1116 of 2332 eyes
      (47.9%) that underwent keratoplasty at our institution. Guttae were identified in
      42 of 946 eyes (4.44%) following penetrating or endothelial keratoplasty, and in
      3 of 170 eyes (1.76%) following anterior lamellar keratoplasty. Twenty-seven of
      these photos demonstrated a few isolated scattered guttae, nine showed widespread
      guttae with small patches, and nine demonstrated large patches of guttae. Last
      documented best spectacle-corrected visual acuity did not differ between patients
      with or without guttae (logarithm of the minimum angle of resolution (logMAR)
      0.22+/-0.24 (approximately 20/32) vs 0.29+/-0.45 (approximately 20/40), p=0.25)
      nor did the groups differ in their 24-month postoperative endothelial cell
      density (1633+/-427 vs 1555+/-454 cells/mm(2), p=0.56). No graft with
      postoperative guttae failed during the follow-up period of this study.
      CONCLUSIONS: Guttae can be found in approximately 4% of post-keratoplasty grafts.
      At least for the initial two postoperative years, they do not negatively affect
      vision, endothelial cell density or graft survival.

PMID- 25957377
TI  - A model of the ocular pharmacokinetics involved in the therapy of neovascular age
      related macular degeneration with ranibizumab.
AB  - BACKGROUND: To develop a model of the pharmacokinetics of vascular endothelial
      growth factor (VEGF-A) determined in samples of aqueous humour from patients with
      neovascular age-related macular degeneration (AMD) treated with ranibizumab
      (Lucentis). METHODS: Post hoc analysis of data from 31 eyes of 31 patients with
      AMD treated with ranibizumab gathered in a non-randomised, prospective clinical
      study. VEGF-A concentrations were measured in 440 aqueous humour samples by
      Luminex multiplex bead analysis (Luminex, Austin, Texas, USA). RESULTS: The
      kinetics of recovery of VEGF-A from suppression by ranibizumab were well
      described by a simple model: VEGF-A is produced at a constant individual rate;
      VEGF-A and ranibizumab disperse rapidly within the vitreous chamber and bind with
      a known affinity; both are eliminated at identical rates from the vitreous
      chamber in a constant but individual flow into the anterior chamber, and are
      finally cleared by draining into the peripheral circulation. Average rates of
      VEGF-A production were predicted to be 5.8 fmol/day (range: 2.7-10.1 fmol), and
      elimination half-times predicted to be 3.5 days (range: 2.3-5.5 days). The
      duration of complete VEGF-A suppression in the aqueous humour averaged 41 days
      (range: 28-67 days). CONCLUSIONS: The ocular pharmacokinetics of VEGF-A and
      ranibizumab have been linked for the first time in a simple and plausible model
      which suggests that it might be possible to anticipate individual VEGF-A
      suppression times. CLINICAL TRIAL NUMBER: NCT01213667.

PMID- 25957379
TI  - Re: Combined associations of genetic and environmental risk factors: implications
      for prevention of breast cancer.

PMID- 25957380
TI  - Precise and feasible measurements of lateral calcaneal lengthening osteotomies by
      radiostereometric analysis in cadaver feet.
AB  - OBJECTIVES: Lengthening osteotomies of the calcaneus in children are in general
      grafted with bone from the iliac crest. Artificial bone grafts have been
      introduced, however, their structural and clinical durability has not been
      documented. Radiostereometric analysis (RSA) is a very accurate and precise
      method for measurements of rigid body movements including the evaluation of joint
      implant and fracture stability, however, RSA has not previously been used in
      clinical studies of calcaneal osteotomies. We assessed the precision of RSA as a
      measurement tool in a lateral calcaneal lengthening osteotomy (LCLO). METHODS:
      LCLO was performed in six fixed adult cadaver feet. Tantalum markers were
      inserted on each side of the osteotomy and in the cuboideum. Lengthening was done
      with a plexiglas wedge. A total of 24 radiological double examinations were
      obtained. Two feet were excluded due to loose and poorly dispersed markers.
      Precision was assessed as systematic bias and 95% repeatability limits. RESULTS:
      Systematic bias was generally below 0.10 mm for translations. Precision of
      migration measurements was below 0.2 mm for translations in the osteotomy.
      CONCLUSION: RSA is a precise tool for the evaluation of stability in LCLO. Cite
      this article: Bone Joint Res 2015;4:78-83.

PMID- 25957378
TI  - Unifying screening processes within the PROSPR consortium: a conceptual model for
      breast, cervical, and colorectal cancer screening.
AB  - General frameworks of the cancer screening process are available, but none
      directly compare the process in detail across different organ sites. This limits
      the ability of medical and public health professionals to develop and evaluate
      coordinated screening programs that apply resources and population management
      strategies available for one cancer site to other sites. We present a trans-organ
      conceptual model that incorporates a single screening episode for breast,
      cervical, and colorectal cancers into a unified framework based on clinical
      guidelines and protocols; the model concepts could be expanded to other organ
      sites. The model covers four types of care in the screening process: risk
      assessment, detection, diagnosis, and treatment. Interfaces between different
      provider teams (eg, primary care and specialty care), including communication and
      transfer of responsibility, may occur when transitioning between types of care.
      Our model highlights across each organ site similarities and differences in
      steps, interfaces, and transitions in the screening process and documents the
      conclusion of a screening episode. This model was developed within the National
      Cancer Institute-funded consortium Population-based Research Optimizing Screening
      through Personalized Regimens (PROSPR). PROSPR aims to optimize the screening
      process for breast, cervical, and colorectal cancer and includes seven research
      centers and a statistical coordinating center. Given current health care reform
      initiatives in the United States, this conceptual model can facilitate the
      development of comprehensive quality metrics for cancer screening and promote
      trans-organ comparative cancer screening research. PROSPR findings will support
      the design of interventions that improve screening outcomes across multiple
      cancer sites. 

PMID- 25957381
TI  - Activity of ceftazidime/avibactam against isogenic strains of Escherichia coli
      containing KPC and SHV beta-lactamases with single amino acid substitutions in
      the Omega-loop.
AB  - OBJECTIVES: The objective of this study was to explore the activity of
      ceftazidime and ceftazidime/avibactam against a collection of isogenic strains of
      Escherichia coli DH10B possessing SHV and KPC beta-lactamases containing single
      amino acid substitutions in the Omega-loop (residues 164-179). METHODS:
      Ceftazidime and ceftazidime/avibactam MICs were determined by the agar dilution
      method for a panel of isogenic E. coli strains expressing SHV-1 and KPC-2 with
      amino acid substitutions at positions 164, 167, 169 or 179. Two KPC-2 beta
      lactamase variants that possessed elevated MICs of ceftazidime/avibactam were
      selected for further biochemical analyses. RESULTS: Avibactam restored
      susceptibility to ceftazidime for all Omega-loop variants of SHV-1 with MICs <8
      mg/L. In contrast, several of the Arg164 and Asp179 variants of KPC-2
      demonstrated MICs of ceftazidime/avibactam >8 mg/L. beta-Lactamase kinetics
      showed that the Asp179Asn variant of KPC-2 demonstrated enhanced kinetic
      properties against ceftazidime. The Ki app, k2/K and koff of the Arg164Ala and
      Asp179Asn variant KPC-2 beta-lactamases indicated that avibactam effectively
      inhibited these enzymes. CONCLUSIONS: Several KPC-2 variants demonstrating
      ceftazidime resistance as a result of single amino acid substitutions in the
      Omega-loop were not susceptible to ceftazidime/avibactam (MICs >8 mg/L). We
      hypothesize that this observation is due to the stabilizing interactions (e.g.
      hydrogen bonds) of ceftazidime within the active site of variant beta-lactamases
      that prevent avibactam from binding to and inhibiting the beta-lactamase. As
      ceftazidime/avibactam is introduced into the clinic, monitoring for new KPC-2
      variants that may exhibit increased ceftazidime kinetics as well as resistance to
      this novel antibiotic combination will be important.

PMID- 25957383
TI  - Pharmacokinetics of high dosage of linezolid in two morbidly obese patients.

PMID- 25957382
TI  - Identification of dfrA14 in two distinct plasmids conferring trimethoprim
      resistance in Actinobacillus pleuropneumoniae.
AB  - OBJECTIVES: The objective of this study was to determine the distribution and
      genetic basis of trimethoprim resistance in Actinobacillus pleuropneumoniae
      isolates from pigs in England. METHODS: Clinical isolates collected between 1998
      and 2011 were tested for resistance to trimethoprim and sulphonamide. The genetic
      basis of trimethoprim resistance was determined by shotgun WGS analysis and the
      subsequent isolation and sequencing of plasmids. RESULTS: A total of 16 (out of
      106) A. pleuropneumoniae isolates were resistant to both trimethoprim (MIC >32
      mg/L) and sulfisoxazole (MIC >=256 mg/L), and a further 32 were resistant only to
      sulfisoxazole (MIC >=256 mg/L). Genome sequence data for the trimethoprim
      resistant isolates revealed the presence of the dfrA14 dihydrofolate reductase
      gene. The distribution of plasmid sequences in multiple contigs suggested the
      presence of two distinct dfrA14-containing plasmids in different isolates, which
      was confirmed by plasmid isolation and sequencing. Both plasmids encoded
      mobilization genes, the sulphonamide resistance gene sul2, as well as dfrA14
      inserted into strA, a streptomycin-resistance-associated gene, although the gene
      order differed between the two plasmids. One of the plasmids further encoded the
      strB streptomycin-resistance-associated gene. CONCLUSIONS: This is the first
      description of mobilizable plasmids conferring trimethoprim resistance in A.
      pleuropneumoniae and, to our knowledge, the first report of dfrA14 in any member
      of the Pasteurellaceae. The identification of dfrA14 conferring trimethoprim
      resistance in A. pleuropneumoniae isolates will facilitate PCR screens for
      resistance to this important antimicrobial.

PMID- 25957384
TI  - Within-host diversity of MRSA antimicrobial resistances.
AB  - OBJECTIVES: MRSA is a major antimicrobial resistance (AMR) pathogen. The
      reservoir of infecting isolates is colonization, which is the site of
      evolutionary selection. The aim was to identify if AMRs in colonizing MRSA
      populations diversified and potential mechanisms of resistance gene transfer in
      vivo. METHODS: Nasal swabs from 38 MRSA carriers admitted to hospital were plated
      and 20 individual colonies from each patient tested for phenotypic antibiotic
      susceptibility and genetically for lineage, carriage of four prophages and three
      plasmid families. Free bacteriophages were detected in swabs as well as their
      capacity for transducing resistance genes. RESULTS: Nine (24%) patients carried
      phenotypic AMR variants and 24 (63%) carried prophage and plasmid variants. If a
      single colony was selected for testing, the probability of detecting all AMR in
      that patient was 87%. Sixty-four different AMR and mobile genetic element (MGE)
      profiles were detected, mostly in the MRSA CC22 background (where CC stands for
      clonal complex), with up to 8 profiles per patient. Nearly half of the patients
      carried detectable free bacteriophages and phages successfully transduced
      resistance genes between laboratory and patient isolates in vitro. WGS showed
      MRSA core genomes were stable, while AMR and MGEs varied. CONCLUSIONS: 'Clouds'
      of MRSA variants that have acquired or lost AMR and MGEs are common in nasal
      colonizing populations and bacteriophages may play an important role in gene
      transfer. Accurate estimation of AMR and genetic variability has implications for
      diagnostics, epidemiology, antimicrobial stewardship and understanding the
      evolutionary selection of AMR in colonizing populations.

PMID- 25957385
TI  - Identification of AKB-48 and 5F-AKB-48 Metabolites in Authentic Human Urine
      Samples Using Human Liver Microsomes and Time of Flight Mass Spectrometry.
AB  - The occurrence of structurally related synthetic cannabinoids makes the
      identification of unique markers of drug intake particularly challenging. The aim
      of this study was to identify unique and abundant metabolites of AKB-48 and 5F
      AKB-48 for toxicological screening in urine. Investigations of authentic urine
      samples from forensic cases in combination with human liver microsome (HLM)
      experiments were used for identification of metabolites. HLM incubations of AKB
      48 and 5F-AKB-48 along with 35 urine samples from authentic cases were analyzed
      with liquid chromatography quadrupole tandem time of flight mass spectrometry.
      Using HLMs 41 metabolites of AKB-48 and 37 metabolites of 5F-AKB-48 were
      identified, principally represented by hydroxylation but also ketone formation
      and dealkylation. Monohydroxylated metabolites were replaced by di- and
      trihydroxylated metabolites within 30 min. The metabolites from the HLM
      incubations accounted for on average 84% (range, 67-100) and 91% (range, 71-100)
      of the combined area in the case samples for AKB-48 and 5F-AKB-48, respectively.
      While defluorinated metabolites accounted for on average 74% of the combined area
      after a 5F-AKB-48 intake only a few identified metabolites were shared between
      AKB-48 and 5F-AKB-48, illustrating the need for a systematic approach to identify
      unique metabolites. HLMs in combination with case samples seem suitable for this
      purpose. 

PMID- 25957387
TI  - Metabolic Crosstalk: Interactions between the Phenylpropanoid and Glucosinolate
      Pathways in Arabidopsis.

PMID- 25957386
TI  - Regulation of histone methylation and reprogramming of gene expression in the
      rice inflorescence meristem.
AB  - Rice inflorescence meristem (IM) activity is essential for panicle development
      and grain production. How chromatin and epigenetic mechanisms regulate IM
      activity remains unclear. Genome-wide analysis revealed that in addition to genes
      involved in the vegetative to reproductive transition, many metabolic and protein
      synthetic genes were activated in IM compared with shoot apical meristem and that
      a change in the H3K27me3/H3K4me3 ratio was an important factor for the
      differential expression of many genes. Thousands of genes gained or lost H3K27me3
      in IM, and downregulation of the H3K27 methyltransferase gene SET DOMAIN GROUP
      711 (SDG711) or mutation of the H3K4 demethylase gene JMJ703 eliminated the
      increase of H3K27me3 in many genes. SDG711-mediated H3K27me3 repressed several
      important genes involved in IM activity and many genes that are silent in the IM
      but activated during floral organogenesis or other developmental stages. SDG711
      overexpression augmented IM activity and increased panicle size; suppression of
      SDG711 by RNA interference had the opposite effect. Double knockdown/knockout of
      SDG711 and JMJ703 further reduced panicle size. These results suggest that SDG711
      and JMJ703 have agonistic functions in reprogramming the H3K27me3/H3K4me3 ratio
      and modulating gene expression in the IM. 

PMID- 25957388
TI  - MicroRNAs: new players in inflammatory bowel disease.

PMID- 25957389
TI  - Allogeneic cell transplant expands bone marrow distribution by colonizing
      previously abandoned areas: an FDG PET/CT analysis.
AB  - Mechanisms of hematopoietic reconstitution after bone marrow (BM) transplantation
      remain largely unknown. We applied a computational quantification software
      application to hybrid 18F-fluorodeoxyglucose positron emission tomography
      (PET)/computed tomography (CT) images to assess activity and distribution of the
      hematopoietic system throughout the whole skeleton of recently transplanted
      patients. Thirty-four patients underwent PET/CT 30 days after either adult stem
      cell transplantation (allogeneic cell transplantation [ACT]; n = 18) or cord
      blood transplantation (CBT; n = 16). Our software automatically recognized
      compact bone volume and trabecular bone volume (IBV) in CT slices. Within IBV,
      coregistered PET data were extracted to identify the active BM (ABM) from the
      inactive tissue. Patients were compared with 34 matched controls chosen among a
      published normalcy database. Whole body ABM increased in ACT and CBT when
      compared with controls (12.4 +/- 3 and 12.8 +/- 6.8 vs 8.1 +/- 2.6 mL/kg of ideal
      body weight [IBW], P < .001). In long bones, ABM increased three- and sixfold in
      CBT and ACT, respectively, compared with controls (0.9 +/- 0.9 and 1.7 +/- 2.5 vs
      0.3 +/- 0.3 mL/kg IBW, P < .01). These data document an unexpected distribution
      of transplanted BM into previously abandoned BM sites. 

PMID- 25957390
TI  - The PI3K/mTOR inhibitor PF-04691502 induces apoptosis and inhibits
      microenvironmental signaling in CLL and the Eu-TCL1 mouse model.
AB  - Current treatment strategies for chronic lymphocytic leukemia (CLL) involve a
      combination of conventional chemotherapeutics, monoclonal antibodies, and
      targeted signaling inhibitors. However, CLL remains largely incurable, with drug
      resistance and treatment relapse a common occurrence, leading to the search for
      novel treatments. Mechanistic target of rapamycin (mTOR)-specific inhibitors have
      been previously assessed but their efficacy is limited due to a positive feedback
      loop via mTOR complex 2 (mTORC2), resulting in activation of prosurvival
      signaling. In this study, we show that the dual phosphatidylinositol 3-kinase
      (PI3K)/mTOR inhibitor PF-04691502 does not induce an mTORC2 positive feedback
      loop similar to other PI3K inhibitors but does induce substantial antitumor
      effects. PF-04691502 significantly reduced survival coincident with the induction
      of Noxa and Puma, independently of immunoglobulin heavy chain variable region
      mutational status, CD38, and ZAP-70 expression. PF-04691502 inhibited both anti
      immunoglobulin M-induced signaling and overcame stroma-induced survival signals
      and migratory stimuli from CXCL12. Equivalent in vitro activity was seen in the
      EMU-TCL1 murine model of CLL. In vivo, PF-04691502 treatment of tumor-bearing
      animals resulted in a transient lymphocytosis, followed by a clear reduction in
      tumor in the blood, bone marrow, spleen, and lymph nodes. These data indicate
      that PF-04691502 or other dual PI3K/mTOR inhibitors in development may prove
      efficacious for the treatment of CLL, increasing our armamentarium to
      successfully manage this disease. 

PMID- 25957391
TI  - AMC 048: modified CODOX-M/IVAC-rituximab is safe and effective for HIV-associated
      Burkitt lymphoma.
AB  - The toxicity of dose-intensive regimens used for Burkitt lymphoma prompted
      modification of cyclophosphamide, vincristine, doxorubicin, high-dose
      methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) for
      HIV-positive patients. We added rituximab, reduced and/or rescheduled
      cyclophosphamide and methotrexate, capped vincristine, and used combination
      intrathecal chemotherapy. Antibiotic prophylaxis and growth factor support were
      required; highly active antiretroviral therapy (HAART) was discretionary.
      Thirteen AIDS Malignancy Consortium centers enrolled 34 patients from 2007 to
      2010. Median age was 42 years (range, 19-55 years), 32 of 34 patients were high
      risk, 74% had stage III to IV BL and CD4 count of 195 cells per MUL (range, 0-721
      cells per MUL), and 5 patients (15%) had CD4 <100 cells per MUL. Twenty-six
      patients were receiving HAART; viral load was <100 copies per mL in 12 patients.
      Twenty-seven patients had at least one grade 3 to 5 toxicity, including 20
      hematologic, 14 infectious, and 6 metabolic. None had grade 3 to 4 mucositis.
      Five patients did not complete treatments because of adverse events. Eleven
      patients died, including 1 treatment-related and 8 disease-related deaths. The 1
      year progression-free survival was 69% (95% confidence interval [CI], 51%-82%)
      and overall survival was 72% (95% CI, 53%-84%); 2-year overall survival was 69%
      (95% CI, 50%-82%). Modifications of the CODOX-M/IVAC regimen resulted in a grade
      3 to 4 toxicity rate of 79%, which was lower than that in the parent regimen
      (100%), without grade 3 to 4 mucositis. Despite a 68% protocol completion rate,
      the 1-year survival rate compares favorably with 2 studies that excluded HIV
      positive patients. This trial was registered at http://clinicaltrials.gov as
      #NCT00392834. 

PMID- 25957393
TI  - Central nervous system relapse in peripheral T-cell lymphomas: a Swedish Lymphoma
      Registry study.
AB  - Central nervous system (CNS) relapse in non-Hodgkin lymphoma (NHL) carries a very
      poor prognosis. Risk factors and outcome have been studied in aggressive B-cell
      lymphomas, but very little is known about the risk in peripheral T-cell lymphoma
      (PTCL). We aimed at analyzing risk factors for CNS involvement at first relapse
      or progression, as well as the outcome of these patients, in a large population
      based cohort of patients with PTCL. Twenty-eight out of 625 patients (4.5%)
      developed CNS disease over time. In multivariable analysis, disease
      characteristics at diagnosis independently associated with an increased risk for
      later CNS involvement were involvement of more than 1 extranodal site (hazard
      ratio [HR], 2.60; 95% confidence interval [CI], 1.07-6.29; P = .035) and skin
      (HR, 3.51; 95% CI, 1.26-9.74; P = .016) and gastrointestinal involvement (HR,
      3.06; 95% CI, 1.30-7.18; P = .010). The outcome of relapsed/refractory patients
      was very poor, and CNS involvement was not associated with a significantly worse
      outcome compared with relapsed/refractory patients without CNS involvement in
      multivariable analysis (HR, 1.6; 95% CI, 0.96-2.6; P = .074). The results from
      the present study indicate that CNS relapse in PTCL occurs at a frequency similar
      to what is seen in aggressive B-cell lymphomas, but the poor outcomes in relapse
      are largely driven by systemic rather than CNS disease. 

PMID- 25957392
TI  - SF3B1 mutation identifies a distinct subset of myelodysplastic syndrome with ring
      sideroblasts.
AB  - Refractory anemia with ring sideroblasts (RARS) is a myelodysplastic syndrome
      (MDS) characterized by isolated erythroid dysplasia and 15% or more bone marrow
      ring sideroblasts. Ring sideroblasts are found also in other MDS subtypes, such
      as refractory cytopenia with multilineage dysplasia and ring sideroblasts (RCMD
      RS). A high prevalence of somatic mutations of SF3B1 was reported in these
      conditions. To identify mutation patterns that affect disease phenotype and
      clinical outcome, we performed a comprehensive mutation analysis in 293 patients
      with myeloid neoplasm and 1% or more ring sideroblasts. SF3B1 mutations were
      detected in 129 of 159 cases (81%) of RARS or RCMD-RS. Among other patients with
      ring sideroblasts, lower prevalence of SF3B1 mutations and higher prevalence of
      mutations in other splicing factor genes were observed (P < .001). In
      multivariable analyses, patients with SF3B1 mutations showed significantly better
      overall survival (hazard ratio [HR], .37; P = .003) and lower cumulative
      incidence of disease progression (HR = 0.31; P = .018) compared with SF3B1
      unmutated cases. The independent prognostic value of SF3B1 mutation was retained
      in MDS without excess blasts, as well as in sideroblastic categories (RARS and
      RCMD-RS). Among SF3B1-mutated patients, coexisting mutations in DNA methylation
      genes were associated with multilineage dysplasia (P = .015) but had no effect on
      clinical outcome. TP53 mutations were frequently detected in patients without
      SF3B1 mutation, and were associated with poor outcome. Thus, SF3B1 mutation
      identifies a distinct MDS subtype that is unlikely to develop detrimental
      subclonal mutations and is characterized by indolent clinical course and
      favorable outcome. 

PMID- 25957394
TI  - Antipsychotic medication in schizophrenia: a review.
AB  - INTRODUCTION: Antipsychotic medications are mainstays in the treatment of
      schizophrenia and a range of other psychotic disorders. SOURCES OF DATA: Recent
      meta-analyses of antipsychotic efficacy and tolerability have been included in
      this review, along with key papers on antipsychotic use in schizophrenia and
      other psychotic illnesses. AREAS OF AGREEMENT: The heterogeneity in terms of
      individuals' response to antipsychotic treatment and the current inability to
      predict response leads to a trial-and-error strategy with treatment choice.
      Clozapine is the only effective medication for treatment-resistant schizophrenia.
      AREAS OF CONTROVERSY: There are a significant number of side effects associated
      with antipsychotic use. With a reduction in the frequency of extrapyramidal side
      effects with the use of second-generation antipsychotics, there has been a
      significant shift in the side effect burden, with an increase in the risk of
      cardiometabolic dysfunction. GROWING POINTS: There exist small and robust
      efficacy differences between medications (other than clozapine), and response and
      tolerability to each antipsychotic drug vary, with there being no first-line
      antipsychotic drug that is suitable for all patients. AREAS TIMELY FOR DEVELOPING
      RESEARCH: A focus on the different symptom domains of schizophrenia may lead to
      endophenotypic markers being identified, e.g. for negative symptoms and cognitive
      deficits (as well as for positive symptoms) that can promote the development of
      novel therapeutics, which will rationally target cellular and molecular targets,
      rather than just the dopamine 2 receptor. Future developments will target
      additional processes, including glutamatergic, cholinergic and cannabinoid
      receptor targets and will utilize personalized medicine techniques, such as
      pharmacogenetic variants and biomarkers allowing for a tailored and safer use of
      antipsychotics.

PMID- 25957395
TI  - Personalized reference intervals for platelet count reduce the number of subjects
      with unexplained thrombocytopenia.

PMID- 25957397
TI  - Bureaucracy is forcing GPs to quit under "euphemism of early retirement".

PMID- 25957396
TI  - Resistance to ABT-199 induced by microenvironmental signals in chronic
      lymphocytic leukemia can be counteracted by CD20 antibodies or kinase inhibitors.

PMID- 25957398
TI  - It will take up to 31 years to deliver number of GPs promised by political
      parties, says RCGP.

PMID- 25957399
TI  - Thematic Minireview Series: The State of the Cytoskeleton in 2015.
AB  - The study of cytoskeletal polymers has been an active area of research for more
      than 70 years. However, despite decades of pioneering work by some of the
      brightest scientists in biochemistry, cell biology, and physiology, many central
      questions regarding the polymers themselves are only now starting to be answered.
      For example, although it has long been appreciated that the actin cytoskeleton
      provides contractility and couples biochemical responses with mechanical stresses
      in cells, only recently have we begun to understand how the actin polymer itself
      responds to mechanical loads. Likewise, although it has long been appreciated
      that the microtubule cytoskeleton can be post-translationally modified, only
      recently have the enzymes responsible for these modifications been characterized,
      so that we can now begin to understand how these modifications alter the
      polymerization and regulation of microtubule structures. Even the septins in
      eukaryotes and the cytoskeletal polymers of prokaryotes have yielded new insights
      due to recent advances in microscopy techniques. In this thematic series of
      minireviews, these topics are covered by some of the very same scientists who
      generated these recent insights, thereby providing us with an overview of the
      State of the Cytoskeleton in 2015. 

PMID- 25957400
TI  - Differential Regulation of NOTCH2 and NOTCH3 Contribute to Their Unique Functions
      in Vascular Smooth Muscle Cells.
AB  - Notch signaling is a key regulator of vascular smooth muscle cell (VSMC)
      phenotypes, including differentiation, proliferation, and cell survival. However,
      the exact contribution of the individual Notch receptors has not been thoroughly
      delineated. In this study, we identify unique roles for NOTCH2 and NOTCH3 in
      regulating proliferation and cell survival in cultured VSMCs. Our results
      indicate that NOTCH2 inhibits PDGF-B-dependent proliferation and its expression
      is decreased by PDGF-B. In contrast, NOTCH3 promotes proliferation and receptor
      expression is increased by PDGF-B. Additionally, data show that NOTCH3, but not
      NOTCH2 protects VSMCs from apoptosis and apoptosis mediators degrade NOTCH3
      protein. We identified three pro-survival genes specifically regulated by NOTCH3
      in cultured VSMCs and in mouse aortas. This regulation is mediated through MAP
      kinase signaling, which we demonstrate can be activated by NOTCH3, but not
      NOTCH2. Overall, this study highlights discrete roles for NOTCH2 and NOTCH3 in
      VSMCs and connects these roles to specific upstream regulators that control their
      expression. 

PMID- 25957401
TI  - Septin Form and Function at the Cell Cortex.
AB  - Septins are GTP-binding proteins that form filaments and higher-order structures
      on the cell cortex of eukaryotic cells and associate with actin and microtubule
      cytoskeletal networks. When assembled, septins coordinate cell division and
      contribute to cell polarity maintenance and membrane remodeling. These functions
      manifest themselves via scaffolding of cytosolic proteins and cytoskeletal
      networks to specific locations on membranes and by forming diffusional barriers
      that restrict lateral diffusion of proteins embedded in membranes. Notably, many
      neurodegenerative diseases and cancers have been characterized as having
      misregulated septins, suggesting that their functions are relevant to diverse
      diseases. Despite the importance of septins, little is known about what features
      of the plasma membrane influence septin recruitment and alternatively, how
      septins influence plasma membrane properties. Septins have been localized to the
      cell cortex at the base of cilia, the mother-bud neck of yeast, and branch points
      of filamentous fungi and dendritic spines, in cleavage furrows, and in retracting
      membrane protrusions in mammalian cells. These sites all possess some degree of
      curvature and are likely composed of distinct lipid pools. Depending on the
      context, septins may act alone or in concert with other cytoskeletal elements to
      influence and sense membrane properties. The degree to which septins react to
      and/or induce changes in shape and lipid composition are discussed here. As
      septins are an essential player in basic biology and disease, understanding the
      interplay between septins and the plasma membrane is critical and may yield new
      and unexpected functions. 

PMID- 25957402
TI  - DAP12 Stabilizes the C-terminal Fragment of the Triggering Receptor Expressed on
      Myeloid Cells-2 (TREM2) and Protects against LPS-induced Pro-inflammatory
      Response.
AB  - Triggering receptor expressed on myeloid cells 2 (TREM2) is a DAP12-associated
      receptor expressed in microglia, macrophages, and other myeloid-derived cells.
      Previous studies have suggested that TREM2/DAP12 signaling pathway reduces
      inflammatory responses and promotes phagocytosis of apoptotic neurons. Recently,
      TREM2 has been identified as a risk gene for Alzheimer disease (AD). Here, we
      show that DAP12 stabilizes the C-terminal fragment of TREM2 (TREM2-CTF), a
      substrate for gamma-secretase. Co-expression of DAP12 with TREM2 selectively
      increased the level of TREM2-CTF with little effects on that of full-length
      TREM2. The interaction between DAP12 and TREM2 is essential for TREM2-CTF
      stabilization as a mutant form of DAP12 with disrupted interaction with TREM2
      failed to exhibit such an effect. Silencing of either Trem2 or Dap12 gene
      significantly exacerbated pro-inflammatory responses induced by
      lipopolysaccharides (LPS). Importantly, overexpression of either full-length
      TREM2 or TREM2-CTF reduced LPS-induced inflammatory responses. Taken together,
      our results support a role of DAP12 in stabilizing TREM2-CTF, thereby protecting
      against excessive pro-inflammatory responses. 

PMID- 25957403
TI  - Osmotic Stress Reduces Ca2+ Signals through Deformation of Caveolae.
AB  - Caveolae are membrane invaginations that can sequester various signaling
      proteins. Caveolae have been shown to provide mechanical strength to cells by
      flattening to accommodate increased volume when cells are subjected to hypo
      osmotic stress. We have previously found that caveolin, the main structural
      component of caveolae, specifically binds Galphaq and stabilizes its activation
      state resulting in an enhanced Ca(2+) signal upon activation. Here, we show that
      osmotic stress caused by decreasing the osmolarity in half reversibly changes the
      configuration of caveolae without releasing a significant portion of caveolin
      molecules. This change in configuration due to flattening leads to a loss in Cav1
      Galphaq association. This loss in Galphaq/Cav1 association due to osmotic stress
      results in a significant reduction of Galphaq/phospholipase Cbeta-mediated Ca(2+)
      signals. This reduced Ca(2+) response is also seen when caveolae are reduced by
      treatment with siRNA(Cav1) or by dissolving them by methyl-beta-cyclodextran. No
      change in Ca(2+) release with osmotic swelling can be seen when growth factor
      pathways are activated. Taken together, these results connect the mechanical
      deformation of caveolae to Galphaq-mediated Ca(2+) signals. 

PMID- 25957404
TI  - Actin Mechanics and Fragmentation.
AB  - Cell physiological processes require the regulation and coordination of both
      mechanical and dynamical properties of the actin cytoskeleton. Here we review
      recent advances in understanding the mechanical properties and stability of actin
      filaments and how these properties are manifested at larger (network) length
      scales. We discuss how forces can influence local biochemical interactions,
      resulting in the formation of mechanically sensitive dynamic steady states.
      Understanding the regulation of such force-activated chemistries and dynamic
      steady states reflects an important challenge for future work that will provide
      valuable insights as to how the actin cytoskeleton engenders
      mechanoresponsiveness of living cells. 

PMID- 25957405
TI  - Bacterial Filament Systems: Toward Understanding Their Emergent Behavior and
      Cellular Functions.
AB  - Bacteria use homologs of eukaryotic cytoskeletal filaments to conduct many
      different tasks, controlling cell shape, division, and DNA segregation. These
      filaments, combined with factors that regulate their polymerization, create
      emergent self-organizing machines. Here, we summarize the current understanding
      of the assembly of these polymers and their spatial regulation by accessory
      factors, framing them in the context of being dynamical systems. We highlight how
      comparing the in vivo dynamics of the filaments with those measured in vitro has
      provided insight into the regulation, emergent behavior, and cellular functions
      of these polymeric systems. 

PMID- 25957406
TI  - Stress-resistant Translation of Cathepsin L mRNA in Breast Cancer Progression.
AB  - The cysteine protease cathepsin L (CTSL) is often thought to act as a tumor
      promoter by enhancing tumor progression and metastasis. This goes along with
      increased CTSL activity in various tumor entities; however, the mechanisms
      leading to high CTSL levels are incompletely understood. With the help of the
      polyoma middle T oncogene driven breast cancer mouse model expressing a human
      CTSL genomic transgene, we show that CTSL indeed promotes breast cancer
      metastasis to the lung. During tumor formation and progression high expression
      levels of CTSL are maintained by enduring translation of CTSL mRNA.
      Interestingly, human breast cancer specimens expressed the same pattern of 5'
      untranslated region (UTR) splice variants as the transgenic mice and the human
      cancer cell line MDA-MB 321. By polyribosome profiling of tumor tissues and human
      breast cancer cells, we observe an intrinsic resistance of CTSL to stress-induced
      shutdown of translation. This ability can be attributed to all 5' UTR variants of
      CTSL and is not dependent on a previously described internal ribosomal entry site
      motif. In conclusion, we provide in vivo functional evidence for overexpressed
      CTSL as a promoter of lung metastasis, whereas high CTSL levels are maintained
      during tumor progression due to stress-resistant mRNA translation. 

PMID- 25957407
TI  - The Familial British Dementia Mutation Promotes Formation of Neurotoxic Cystine
      Cross-linked Amyloid Bri (ABri) Oligomers.
AB  - Familial British dementia (FBD) is an inherited neurodegenerative disease
      believed to result from a mutation in the BRI2 gene. Post-translational
      processing of wild type BRI2 and FBD-BRI2 result in the production of a 23
      residue long Bri peptide and a 34-amino acid long ABri peptide, respectively, and
      ABri is found deposited in the brains of individuals with FBD. Similarities in
      the neuropathology and clinical presentation shared by FBD and Alzheimer disease
      (AD) have led some to suggest that ABri and the AD-associated amyloid beta
      protein (Abeta) are molecular equivalents that trigger analogous pathogenic
      cascades. But the sequences and innate properties of ABri and Abeta are quite
      different, notably ABri contains two cysteine residues that can form disulfide
      bonds. Thus we sought to determine whether ABri was neurotoxic and if this
      activity was regulated by oxidation and/or aggregation. Crucially, the type of
      oxidative cross-linking dramatically influenced both ABri aggregation and
      toxicity. Cyclization of Bri and ABri resulted in production of biologically
      inert monomers that showed no propensity to assemble, whereas reduced ABri and
      reduced Bri aggregated forming thioflavin T-positive amyloid fibrils that lacked
      significant toxic activity. ABri was more prone to form inter-molecular disulfide
      bonds than Bri and the formation of covalently stabilized ABri oligomers was
      associated with toxicity. These results suggest that extension of the C-terminal
      of Bri causes a shift in the type of disulfide bonds formed and that structures
      built from covalently cross-linked oligomers can interact with neurons and
      compromise their function and viability. 

PMID- 25957408
TI  - Structural Studies of Potassium Transport Protein KtrA Regulator of Conductance
      of K+ (RCK) C Domain in Complex with Cyclic Diadenosine Monophosphate (c-di-AMP).
AB  - Although it was only recently identified as a second messenger, c-di-AMP was
      found to have fundamental importance in numerous bacterial functions such as ion
      transport. The potassium transporter protein, KtrA, was identified as a c-di-AMP
      receptor. However, the co-crystallization of c-di-AMP with the protein has not
      been studied. Here, we determined the crystal structure of the KtrA RCK_C domain
      in complex with c-di-AMP. The c-di-AMP nucleotide, which adopts a U-shaped
      conformation, is bound at the dimer interface of RCK_C close to helices alpha3
      and alpha4. c-di-AMP interacts with KtrA RCK_C mainly by forming hydrogen bonds
      and hydrophobic interactions. c-di-AMP binding induces the contraction of the
      dimer, bringing the two monomers of KtrA RCK_C into close proximity. The KtrA
      RCK_C was able to interact with only c-di-AMP, but not with c-di-GMP, 3',3-cGAMP,
      ATP, and ADP. The structure of the KtrA RCK_C domain and c-di-AMP complex would
      expand our understanding about the mechanism of inactivation in Ktr transporters
      governed by c-di-AMP. 

PMID- 25957409
TI  - Intermediate Filaments Play a Pivotal Role in Regulating Cell Architecture and
      Function.
AB  - Intermediate filaments (IFs) are composed of one or more members of a large
      family of cytoskeletal proteins, whose expression is cell- and tissue type
      specific. Their importance in regulating the physiological properties of cells is
      becoming widely recognized in functions ranging from cell motility to signal
      transduction. IF proteins assemble into nanoscale biopolymers with unique strain
      hardening properties that are related to their roles in regulating the mechanical
      integrity of cells. Furthermore, mutations in the genes encoding IF proteins
      cause a wide range of human diseases. Due to the number of different types of IF
      proteins, we have limited this short review to cover structure and function
      topics mainly related to the simpler homopolymeric IF networks composed of
      vimentin, and specifically for diseases, the related muscle-specific desmin IF
      networks. 

PMID- 25957410
TI  - Building the Microtubule Cytoskeleton Piece by Piece.
AB  - The microtubule (MT) cytoskeleton gives cells their shape, organizes the cellular
      interior, and segregates chromosomes. These functions rely on the precise
      arrangement of MTs, which is achieved by the coordinated action of MT-associated
      proteins (MAPs). We highlight the first and most important examples of how
      different MAP activities are combined in vitro to create an ensemble function
      that exceeds the simple addition of their individual activities, and how the
      Xenopus laevis egg extract system has been utilized as a powerful intermediate
      between cellular and purified systems to uncover the design principles of self
      organized MT networks in the cell. 

PMID- 25957411
TI  - Mutations in Nature Conferred a High Affinity Phosphatidylinositol 4,5
      Bisphosphate-binding Site in Vertebrate Inwardly Rectifying Potassium Channels.
AB  - All vertebrate inwardly rectifying potassium (Kir) channels are activated by
      phosphatidylinositol 4,5-bisphosphate (PIP2) (Logothetis, D. E., Petrou, V. I.,
      Zhang, M., Mahajan, R., Meng, X. Y., Adney, S. K., Cui, M., and Baki, L. (2015)
      Annu. Rev. Physiol. 77, 81-104; Furst, O., Mondou, B., and D'Avanzo, N. (2014)
      Front. Physiol. 4, 404-404). Structural components of a PIP2-binding site are
      conserved in vertebrate Kir channels but not in distantly related animals such as
      sponges and sea anemones. To expand our understanding of the structure-function
      relationships of PIP2 regulation of Kir channels, we studied AqKir, which was
      cloned from the marine sponge Amphimedon queenslandica, an animal that represents
      the phylogenetically oldest metazoans. A requirement for PIP2 in the maintenance
      of AqKir activity was examined in intact oocytes by activation of a co-expressed
      voltage-sensing phosphatase, application of wortmannin (at micromolar
      concentrations), and activation of a co-expressed muscarinic acetylcholine
      receptor. All three mechanisms to reduce the availability of PIP2 resulted in
      inhibition of AqKir current. However, time-dependent rundown of AqKir currents in
      inside-out patches could not be re-activated by direct application to the inside
      membrane surface of water-soluble dioctanoyl PIP2, and the current was
      incompletely re-activated by the more hydrophobic arachidonyl stearyl PIP2. When
      we introduced mutations to AqKir to restore two positive charges within the
      vertebrate PIP2-binding site, both forms of PIP2 strongly re-activated the mutant
      sponge channels in inside-out patches. Molecular dynamics simulations validate
      the additional hydrogen bonding potential of the sponge channel mutants. Thus,
      nature's mutations conferred a high affinity activation of vertebrate Kir
      channels by PIP2, and this is a more recent evolutionary development than the
      structures that explain ion channel selectivity and inward rectification. 

PMID- 25957413
TI  - The immunologically active oligosaccharides isolated from wheatgrass modulate
      monocytes via Toll-like receptor-2 signaling.

PMID- 25957412
TI  - Writing and Reading the Tubulin Code.
AB  - Microtubules give rise to intracellular structures with diverse morphologies and
      dynamics that are crucial for cell division, motility, and differentiation. They
      are decorated with abundant and chemically diverse posttranslational
      modifications that modulate their stability and interactions with cellular
      regulators. These modifications are important for the biogenesis and maintenance
      of complex microtubule arrays such as those found in spindles, cilia, neuronal
      processes, and platelets. Here we discuss the nature and subcellular distribution
      of these posttranslational marks whose patterns have been proposed to constitute
      a tubulin code that is interpreted by cellular effectors. We review the enzymes
      responsible for writing the tubulin code, explore their functional consequences,
      and identify outstanding challenges in deciphering the tubulin code. 

PMID- 25957414
TI  - Identification of transcriptional factors and key genes in primary osteoporosis
      by DNA microarray.
AB  - BACKGROUND: A number of genes have been identified to be related with primary
      osteoporosis while less is known about the comprehensive interactions between
      regulating genes and proteins. We aimed to identify the differentially expressed
      genes (DEGs) and regulatory effects of transcription factors (TFs) involved in
      primary osteoporosis. MATERIAL/METHODS: The gene expression profile GSE35958 was
      obtained from Gene Expression Omnibus database, including 5 primary osteoporosis
      and 4 normal bone tissues. The differentially expressed genes between primary
      osteoporosis and normal bone tissues were identified by the same package in R
      language. The TFs of these DEGs were predicted with the Essaghir A method. DAVID
      (The Database for Annotation, Visualization and Integrated Discovery) was applied
      to perform the GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and
      Genomes) pathway enrichment analysis of DEGs. After analyzing regulatory effects,
      a regulatory network was built between TFs and the related DEGs. RESULTS: A total
      of 579 DEGs was screened, including 310 up-regulated genes and 269 down-regulated
      genes in primary osteoporosis samples. In GO terms, more up-regulated genes were
      enriched in transcription regulator activity, and secondly in transcription
      factor activity. A total 10 significant pathways were enriched in KEGG analysis,
      including colorectal cancer, Wnt signaling pathway, Focal adhesion, and MAPK
      signaling pathway. Moreover, total 7 TFs were enriched, of which CTNNB1, SP1, and
      TP53 regulated most up-regulated DEGs. CONCLUSIONS: The discovery of the enriched
      TFs might contribute to the understanding of the mechanism of primary
      osteoporosis. Further research on genes and TFs related to the WNT signaling
      pathway and MAPK pathway is urgent for clinical diagnosis and directing treatment
      of primary osteoporosis.

PMID- 25957415
TI  - CSN6 deregulation impairs genome integrity in a COP1-dependent pathway.
AB  - Understanding genome integrity and DNA damage response are critical to cancer
      treatment. In this study, we identify CSN6's biological function in regulating
      genome integrity. Constitutive photomorphogenic 1 (COP1), an E3 ubiquitin ligase
      regulated by CSN6, is downregulated by DNA damage, but the biological
      consequences of this phenomenon are poorly understood. p27(Kip1) is a critical
      CDK inhibitor involved in cell cycle regulation, but its response to DNA damage
      remains unclear. Here, we report that p27(Kip1) levels are elevated after DNA
      damage, with concurrent reduction of COP1 levels. Mechanistic studies showed that
      during DNA damage response COP1's function as an E3 ligase of p27 is compromised,
      thereby reducing the ubiquitin-mediated degradation of p27(Kip1). Also, COP1
      overexpression leads to downregulation of p27(Kip1), thereby promoting the
      expression of mitotic kinase Aurora A. Overexpression of Aurora A correlates with
      poor survival. These findings provide new insight into CSN6-COP1-p27(Kip1)-Aurora
      A axis in DNA damage repair and tumorigenesis.

PMID- 25957416
TI  - Activation of hypoxia signaling induces phenotypic transformation of glioma
      cells: implications for bevacizumab antiangiogenic therapy.
AB  - Glioblastoma (GBM) is the most common and deadly primary brain tumor in adults.
      Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth
      factor (VEGF), can attenuate tumor-associated edema and improve patient symptoms
      but based on magnetic resonance imaging, is associated with non-enhancing tumor
      progression and possibly gliosarcoma differentiation. To gain insight into these
      findings, we investigated the role of hypoxia and epithelial-mesenchymal
      transition (EMT)-associated proteins in GBM. Tumor markers of hypoxia and EMT
      were upregulated in bevacizumab-treated tumors from GBM patients compared to
      untreated counterparts. Exposure of glioma cells to 1% oxygen tension increased
      cell proliferation, expression of EMT-associated proteins and enhanced cell
      migration in vitro. These phenotypic changes were significantly attenuated by
      pharmacologic knockdown of hypoxia-inducible Factor 1alpha (HIF1alpha) or
      HIF2alpha, indicating that HIFs represent a therapeutic target for mesenchymal
      GBM cells. These findings provide insights into potential development of novel
      therapeutic targeting of angiogenesis-specific pathways in GBM. 

PMID- 25957419
TI  - Oxidative stress in chronic kidney disease.
AB  - Patients with chronic kidney disease (CKD) have high incidence rates of
      cardiovascular disease and malignancy. Several factors contribute to these
      conditions. Structural characteristics in CKD, loss of renal energy, and uremia
      result in an imbalance between free radical production and antioxidant defenses.
      Also, CKD patients usually have multiple cardiovascular risk factors like
      diabetes mellitus, dyslipidemia, and hypertension. These conditions are
      associated with oxidative stress, which can trigger the inflammatory process and
      accelerate renal injury progression. There are some clinical biomarkers to detect
      oxidative stress and antioxidant status in CKD patients. Antioxidant therapies
      may be beneficial in reducing oxidative stress, lowering uremic cardiovascular
      toxicity, and improving survival. Therefore, their roles in CKD patients have
      been evaluated in several studies as a new target for therapeutic intervention.
      This review provides an overview of oxidative stress mechanisms, clinical
      squeals, biomarkers, and possible antioxidant therapies in CKD patients. 

PMID- 25957417
TI  - Intraperitoneal administration of tumor-targeting Salmonella typhimurium A1-R
      inhibits disseminated human ovarian cancer and extends survival in nude mice.
AB  - Peritoneal disseminated cancer is highly treatment resistant. We here report the
      efficacy of intraperitoneal (i.p.) administration of tumor-targeting Salmonella
      typhimurium A1-R in a nude mouse model of disseminated human ovarian cancer. The
      mouse model was established by intraperitoneal injection of the human ovarian
      cancer cell line SKOV3-GFP. Seven days after implantation, mice were treated with
      S. typhimurium A1-R via intravenous (i.v.) or i.p. administration at the same
      dose, 5 * 10(7) CFU, once per week. Both i.v. and i.p. treatments effected
      prolonged survival compared with the untreated control group (P=0.025 and
      P<0.001, respectively). However, i.p. treatment was less toxic than i.v.
      TREATMENT: Tumor-specific targeting of S. typhimurium A1-R was confirmed with
      bacterial culture from tumors and various organs and tumor or organ colony
      formation after i.v. or i.p. injection. Selective tumor targeting was most
      effective with i.p. administration. The results of the present study show S.
      typhimurium A1-R has promising clinical potential for disseminated ovarian
      cancer, especially via i.p. administration.

PMID- 25957420
TI  - Prolonging nephrogenesis in preterm infants: a new approach for prevention of
      kidney disease in adulthood?
AB  - Chronic kidney disease represents a dramatic worldwide resource-consuming
      problem. This problem is of increasing importance even in preterm infants, since
      nephrogenesis may go on only for a few weeks (4 to 6 weeks) after birth. Recent
      literature focusing on traditional regenerative medicine does not take into
      account the presence of a high number of active endogenous stem cells in the
      preterm kidney, which represents a unique opportunity for starting regenerative
      medicine in the perinatal period. Pluripotent cells of the blue strip have the
      capacity to generate new nephrons, improving kidney function in neonates and
      potentially protecting them from developing chronic kidney disease and end-stage
      renal disease in adulthood. There is a marked interindividual neonatal
      variability of nephron numbers. Moreover, the renal stem/progenitor cells appear
      as densely-packed small cells with scant cytoplasm, giving rise to a blue
      appearing strip in hematoxylin-eosin-stained kidney sections ("the blue strip").
      There are questions concerning renal regenerative medicine: among preliminary
      data, the simultaneous expression of Wilms tumor 1 and thymosin beta4 in
      stem/progenitor cells of the neonatal kidney may bring new prospects for renal
      regeneration applied to renal stem cells that reside in the kidney itself. A
      potential approach could be to prolong the 6 weeks of postnatal renal growth of
      nephrons or to accelerate the growth of nephrons during the 6 weeks or both.
      Considering what we know today about perinatal programming, this could be an
      important step for the future to reduce the incidence and global health impact of
      chronic kidney disease. 

PMID- 25957418
TI  - Ectopic expression of a novel CD22 splice-variant regulates survival and
      proliferation in malignant T cells from cutaneous T cell lymphoma (CTCL)
      patients.
AB  - CD22 is a member of the Sialic acid-binding Ig-like lectin (Siglec) family of
      lectins described to be exclusively present in B lymphocytes and B cell-derived
      neoplasms. Here, we describe a novel splice form of CD22 (designated CD22a??N),
      which lacks the N-terminal domain as demonstrated by exon-specific RT-PCR and
      differential recognition by anti-CD22 antibodies. Importantly, CD22a??N mRNA is
      expressed in skin lesions from 39 out of 60 patients with cutaneous T cell
      lymphoma (CTCL), whereas few patients (6 out of 60) expresses full-length, wild
      type CD22 (CD22wt). In addition, IHC staining of tumor biopsies confirmed the
      expression of CD22 in CD4+ T cells. Moreover, four out of four malignant T cell
      lines express CD22: Two cell lines express CD22a??N (MyLa2059 and PB2B) and two
      express CD22wt (MAC-1 and MAC-2A). siRNA-mediated silencing of CD22 impairs
      proliferation and survival of malignant T cells, demonstrating a functional role
      for both CD22a??N and CD22wt in these cells.In conclusion, we provide the first
      evidence for an ectopic expression of CD22 and a novel splice variant regulating
      malignant proliferation and survival in CTCL. Analysis of expression and function
      of CD22 in cutaneous lymphomas may form the basis for development of novel
      targeted therapies for our patients. 

PMID- 25957422
TI  - Localized cystic disease of kidney.

PMID- 25957421
TI  - A multilevel model for services provided to patients with chronic kidney disease.
AB  - Chronic kidney disease (CKD) is a general health problem with high rates of
      mortality and morbidity. The increasing prevalence of CKD has led to the
      recognition of the fact that it needs special care. One approach to CKD
      management is to present a model of care for the disease. A model of care for CKD
      was developed by drawing on the literature, including guidelines for CKD care,
      and by using previous experiences in providing care for patients with diabetes
      mellitus and CKD. The model focuses on training, identification of patients,
      care, follow-up, and evaluation of patients. In this study, two levels were
      defined for providing care to patients with CKD. The first level involves care
      provided by family physicians, while the second level was defined as community
      health services for CKD. Establishment of at least 1 CKD community health service
      at each capital city of any province seems to be an effective factor in improving
      services provided to patients with CKD. 

PMID- 25957423
TI  - Role of vitamin D in improvement in changes of podocyte P-cadherin/beta-catenin
      complex induced by diabetic conditions.
AB  - INTRODUCTION: This study aimed to investigate the effect of vitamin D on the
      pathologic changes of podocyte beta-catenin and P-cadherin and podocyte
      permeability induced by diabetic conditions. MATERIALS AND METHODS: We cultured
      mouse podocytes under normal glucose (5 mM, control); high glucose (HG, 30 mM);
      advanced glycosylation end products (AGE)-added; and HG plus AGE-added conditions
      and treated with vitamin D. The distribution of podocyte beta-catenin and P
      cadherin was shown by confocal microscopy, and protein levels of beta-catenin and
      P-cadherin by Western blotting. Podocytes were incubated with vitamin D at the
      concentrations of 10 nM and 50 nM for 6, 24, and 48 hours. RESULTS: The dextran
      filtration through monolayered podocytes tended to increase in AGE and HG
      condition compared to that in B5 at 16 hours in permeability assay, which was
      improved by vitamin D. In confocal imaging, the distribution of beta-catenin and
      P-cadherin were internally concentrated by diabetic conditions, which was
      ameliorated by vitamin D. In Western blotting, HG and AGE decreased beta-catenin
      protein levels at 6, 24, and 48 hours and vitamin D improved the decreased beta
      catenin protein levels at 6, 24, and 48 hours. Advanced glycosylation end
      products also decreased P-cadherin protein amount by 22.9% and 59.1% (P <.01) at
      24 hours, respectively, which was improved by vitamin D. CONCLUSIONS: Our results
      suggest that HG and AGE have an influence on the redistribution of beta-catenin
      and P-cadherin and amount of beta-catenin protein of podocytes, thereby causing
      hyperpermeability, which can be reversed by vitamin D.

PMID- 25957424
TI  - Attenuation of Inflammation by Emodin in Lipopolysaccharide-induced Acute Kidney
      Injury via Inhibition of Toll-like Receptor 2 Signal Pathway.
AB  - INTRODUCTION: Emodin, an anthraquinone derivative from the Chinese herb Radix et
      Rhizoma Rhe, has been reported to possess anti-inflammatory property in vivo and
      in vitro. However, the effect of emodin on inflammation in lipopolysaccharide
      (LPS)-induced acute kidney injury as an immunomodulator has yet to be determined.
      This study aimed to investigate whether emodin had protective effects against LPS
      induced acute kidney injury by inhibiting toll-like receptor 2 (TLR2) signal
      pathway in normal rat kidney epithelial cells (NRK-52E). MATERIALS AND METHODS:
      The NRK-52E cells were incubated with LPS with and without the indicated
      concentrations of emodin for 24 hours. The TLR2 and NF-kappaB protein level was
      detected by Western blot method. Tumor necrosis factor (TNF)-alpha, interleukin
      (IL)-1beta, and IL-6 protein levels were measured using an enzyme-linked
      immunosorbent assay. The mRNA expression of TLR2, NF-kappaB, TNF-alpha, IL-1beta,
      and IL-6 was detected using a real-time polymersase chain reaction. RESULTS: A
      concentration of 102 ng/mL of LPS significantly upregulated mRNA and protein
      levels of TLR2 and NF-kappaB and increased TNF-alpha, IL-1beta, and IL-6 mRNA and
      protein levels. At doses of 20 uM and 40 uM, emodin was able to inhibit LPS
      induced TLR2, NF-kappaB, TNF-alpha, IL-1beta and IL-6 mRNA and protein
      expressions in cultured NRK-52E cells. CONCLUSIONS: These results demonstrate
      that an elevated expression of inflammatory cytokines and TLR2 in cells
      stimulated by LPS were simultaneously inhibited by emodin. Therefore, emodin
      attenuates the inflammation by inhibiting TLR2-mediated NF-kappaB signal pathway,
      which may contribute to the immune inflammation regulation of emodin in LPS
      induced acute kidney injury.

PMID- 25957425
TI  - Aldosterone Synthase CYP11B2 Gene Promoter Polymorphism in a Turkish Population
      With Chronic Kidney Disease.
AB  - INTRODUCTION: It has been shown that gene polymorphisms influence the development
      and progression of chronic kidney disease (CKD). Many studies have indicated that
      aldosterone synthase CYP11B2 gene polymorphism (-344C>T) influences the
      aldosterone level, urinary aldosterone excretion, blood pressure, and left
      ventricular size and mass. We aimed to investigate whether there is an effect of
      CYP11B2 -344 C>T polymorphism on the development of CKD in a Turkish population.
      MATERIAL AND METHODS: A total of 240 patients with stage 5 CKD and 240 age- and
      sex-matched healthy individuals were included in the study. Genotyping of CYP11B2
      gene -344 T>C promoter polymorphism was carried out using polymerase chain
      reaction and restriction fragment length polymorphism methods. RESULTS: No
      significant differences were found in the genotype distribution of CYP11B2 -344
      C>T polymorphism between the patients and controls; however, -344 C>T
      polymorphism was significantly more frequent among the CKD patients with diabetes
      mellitus as compared to those with it (P = .02). Diabetic CKD patients with TC
      genotype had a 2-fold increased risk for development of the disease than the CKD
      patients without diabetes mellitus (odds ratio, 2.21; 95% confidence interval,
      1.04 to 4.67). CONCLUSIONS: Our study suggests that the CYP11B2 gene -344 C>T
      polymorphism may have an effect on the development of CKD in diabetic patients.

PMID- 25957426
TI  - Paradoxical effects of atorvastatin on renal tubular cells: an experimental
      investigation.
AB  - INTRODUCTION: Atorvastatin has antioxidant activity and has been reported to
      increase blood antioxidant capacity. This study aimed to evaluate the effect of
      different doses of atorvastatin on gentamicin-induced kidney injury. MATERIALS
      AND METHODS: In this experimental study, 30 male Wistar rats were designated into
      6 equal groups for a 7-day period of intraperitoneal injections of gentamicin and
      atorvastatin. Group 1 received gentamicin, 80 mg/kg. Group 2 received phosphate
      buffer as the vehicle of atorvastatin. All rats in groups 3, 4, and 5 received
      gentamicin, 80 mg/kg/d, and then, after a 1-hour interval, atorvastatin was
      injected for 7 days as follow: group 3, 10 mg/kg/d; group 4, 50 mg/kg/d; and
      group 5, 150 mg/kg/d. Rats in group 6 received only 150 mg of atorvastatin. On
      the 8th day, blood samples were collected for evaluation of creatinine and blood
      urea nitrogen levels, and the animals' kidneys were dissected out for
      histopathological examinations. RESULTS: Morphological damages to the tubular
      cells in groups 3 and 4 were less than those in groups 1 and 5. Injuries to the
      renal tubular cells in the rats of group 5 (gentamicin and atorvastatin, 150
      mg/kg/d) and in group 6 (atorvastatin 150 mg/kg/d alone) were more extensive than
      those in group 1. CONCLUSIONS: The none-dose-dependent effect of atorvastatin in
      inducing renal tubular cell protection and renal tubular toxicity of atorvastatin
      in higher dose suggest administration of low-dose atorvastatin in critical
      conditions associated with renal tubular cell protection.

PMID- 25957427
TI  - Effect of infliximab on renal injury due to methotrexate in rat.
AB  - INTRODUCTION: Methotrexate, an antagonist of folic acid used in the treatment of
      many cancers and inflammatory diseases, is associated with side effects that
      limit its usage. Infliximab has been reported to have a protective effect against
      nephrotoxicity induced by some drugs and ischemic reperfusion. We aimed to
      investigate whether infliximab has a protective effect against methotrexate
      induced nephrotoxicity. MATERIALS AND METHODS: We administered methotrexate at a
      dose of 20 mg/kg as a single intraperitoneal injection in 10 rats (methotrexate
      group). Another group of 10 rats received a single dose of infliximab, 7 mg/kg,
      intraperitoneally (infliximab group). The methotrexate and infliximab group
      received a similar single injection of infliximab 72 hours prior to methotrexate
      injection. After 72 hours a single dose of methotrexate, 20 mg/kg, was
      administered intraperitoneally. Five days after methotrexate injection, blood
      samples were collected and the kidney tissues were removed for biochemical and
      histological examination. RESULTS: The methotrexate group had significantly
      higher tissue levels of tumor necrosis factor-alpha (P = .008), interleukin-1beta
      (P = .04), nitric oxide (P < .001), and adenosine deaminase (P < .001) than the
      methotrexate and infliximab group after the 5-day study. The methotrexate group
      also had significantly higher total histological scores (P < .001) and carbonic
      anhydrase-II activity (P < .001) when compared to the methotrexate and infliximab
      group. CONCLUSIONS: Infliximab has a strong protective effect against
      methotrexate-induced nephrotoxicity by suppressing cytokines release. It may
      decrease methotrexate-induced nephrotoxicity by regulating carbonic anhydrase-II
      enzyme activities and slowing down purine metabolism.

PMID- 25957428
TI  - A novel mutation pattern of kidney anion exchanger 1 gene in patients with distal
      renal tubular acidosis in Iran.
AB  - INTRODUCTION: Mutations of the anion exchanger 1 (AE1) gene encoding the kidney
      anion exchanger 1 can result in autosomal dominant or autosomal recessive form of
      distal renal tubular acidosis (DRTA). This study aimed to report deletion
      mutations of the AE1 and its impact on Iranian children with DRTA. MATERIALS AND
      METHODS: Twelve children with DRTA referred to Ali Asghar Children Hospital were
      investigated for all AE1 gene exons through polymerase chain reaction
      amplification, DNA sequencing, and bioinformatics analysis. RESULTS: Eleven of 12
      patients (91.7%) showed an alteration in AE1 gene with a real hot spot in its
      exons 11 or 15. Homozygote and heterozygote deletions were confirmed in exon 15
      in 5 (41.7%) and 3 (25.0%), respectively. Two patients (16.7%) showed homozygote
      deletions in exon 11 of AE1 gene, and 1 patient (8.3%) showed point mutation in
      exon 11. The 3-dimensional structures of the native and these mutant kidney AE1
      proteins were determined by the multitemplate method using the Phyre and Hidden
      Markov Model algorithms. CONCLUSIONS: Parents' consanguinity of these patients
      reveals that cousins are at a high risk for DRTA. This study is considered as a
      pilot study showing the importance of AE1 mutations in Iranian children with DRTA
      and further studies is recommended in this geographic region of the world. These
      models suggest that alteration in the structures leads to alteration in function
      and change in the current role of AE1.

PMID- 25957430
TI  - Growth Arrest-specific 6 Protein and Matrix Gla Protein in Hemodialysis Patients.
AB  - INTRODUCTION: Plasma protein growth arrest-specific 6 (GAS6) and matrix Gla
      protein (MGP) are crucial mediators of vascular calcification and are involved in
      the development of vascular complications in chronic kidney diseases. This study
      was set out to investigate the relationship between plasma GAS6 levels and MGP in
      patients with end-stage renal disease on maintenance hemodialysis. MATERIALS AND
      METHODS: Forty-six hemodialysis and 46 healthy individuals with normal kidneys
      were recruited. Plasma GAS6 and MGP concentrations and related biochemical
      factors were quantified as well as collection of data on clinical
      characteristics. RESULTS: Plasma GAS6 levels were significantly higher in the
      hemodialysis patients as compared with the control group (763.52 +/- 187.91 pg/mL
      versus 421.63 +/- 189.91 pg/mL, P < .001). Plasma MGP concentration was
      significantly lower in the hemodialysis patients than the control group (52.35 +/
      12.35 ng/mL versus 6.60 +/- 19.54 ng/mL, P < .001). The levels of GAS6 were
      inversely associated with MGP (r = -0.341, P = .02) in the hemodialysis patients.
      CONCLUSIONS: Increased GAS6 and decreased MGP levels in hemodialysis patients, as
      mediators of induction or prevention of vascular calcification, and their inverse
      correlation may suggest that there might be a role in increased calcification
      process in hemodialysis patients or only as a secondary phenomenon of advanced
      kidney failure. Their direct role on vascular calcification needs further studies
      in the future.

PMID- 25957429
TI  - Diagnostic urinary proteome profile for immunoglobulin a nephropathy.
AB  - INTRODUCTION: Immunoglobulin A (IgA) nephropathy, the most common type of
      glomerulonephritis, is only diagnosed by invasive kidney biopsy. Urine proteome
      panel might help in noninvasive diagnosis and also better understanding of
      pathogenesis of IgA nephropathy. MATERIALS AND METHODS: Second mid-stream urine
      samples of 13 patients with biopsy-proven IgA nephropathy and 8 healthy controls
      were investigated by means of nanoscale liquid chromatography tandem mass
      spectrometry. Multivariate analysis of quantified label-free proteins was
      performed by the principal component analysis and partial least squares models.
      RESULTS: A total number of 493 unique proteins were quantified by nanoscale
      liquid chromatography tandem mass spectrometry, of which 46 proteins were
      considered as putative biomarkers of IgA nephropathy, after multivariate analysis
      and additional filter criterion and comparing the patients and the controls. Some
      of the significant differentially expressed proteins were CD44, glycoprotein 2,
      vasorin, epidermal growth factor, CLM9, protocadherin, utreoglobin, dipeptidyl
      peptidase IV, NHL repeat-containing protein 3, and SLAM family member 5. These
      proteins were related to various involved pathogenic pathways of inflammatory
      response and complement system. CONCLUSIONS: This proteome profile could be
      utilized in the diagnosis of IgA nephropathy. In addition, providing a
      noninvasive diagnostic tool, it may shed light on the pathogenesis of IgA
      nephropathy.

PMID- 25957431
TI  - Adipsic hypernatremic myopathy.
AB  - Chronic hypernatremia due to adipsia is very rare and occasionally presents with
      muscle weakness and rhabdomyolysis. We report a patient with chronic
      hypernatremia without thirst sensation who presented with muscle weakness and was
      treated successfully with prescribed water intake. 

PMID- 25957432
TI  - Nephroquiz 8: perioperative management of paraganglioma.

PMID- 25957433
TI  - Re: association of programmed cell death 1 and programmed cell death 1 ligand
      gene polymorphisms with delayed graft function and acute rejection in kidney
      allograft recipients.

PMID- 25957434
TI  - Bullous Eruption Associated With Dihydropyridines With Cross Reactivity.
AB  - The spectrum of cutaneous eruptions associated with dihydropyridines is
      extensive, varying from exanthemas to severe adverse events. We report a case of
      bullous eruption, one month after starting nicardipine and lercanidipine. The
      same symptoms recurred few days after taking nitrendipine. 

PMID- 25957435
TI  - Androgen deprivation with or without radiation therapy for clinically node
      positive prostate cancer.
AB  - BACKGROUND: Clinically lymph node-positive (cN+) prostate cancer (PCa) is an
      often-fatal disease. Its optimal management remains largely undefined given a
      lack of prospective, randomized data to inform practice. We sought to describe
      modern practice patterns in the management of cN+ PCa and assess the effect of
      adding radiation therapy (RT) to androgen deprivation therapy (ADT) on survival
      using the National Cancer Data Base. METHODS: Patients with cN+ PCa and without
      distant metastases diagnosed between 2004 and 2011 were included. Five-year
      overall survival for patients diagnosed between 2004 and 2006 and treated with
      ADT alone or ADT+RT were compared. Propensity score (PS) matching was used to
      balance baseline characteristics, and Cox multivariate regression analysis was
      used to estimate hazard ratios (HRs) for all-cause mortality. RESULTS: Of 3540
      total patients, 32.2% were treated with ADT alone and 51.4% received ADT+RT.
      Compared with ADT alone, patients treated with ADT+RT were younger and more
      likely to have private insurance, lower comorbidity scores, higher Gleason
      scores, and lower PSA values. After PS matching, 318 patients remained in each
      group. Compared with ADT alone, ADT+RT was associated with a 50% decreased risk
      of five-year all-cause mortality (HR = 0.50, 95% CI = 0.37 to 0.67, two-sided P <
      .001; crude OS rate: 71.5% vs 53.2%). CONCLUSIONS: Using a large national
      database, we have identified a statistically significant survival benefit for
      patients with cN+ PCa treated with ADT+RT. These data, if appropriately validated
      by randomized trials, suggest that a substantial proportion of such patients at
      high risk for prostate cancer death may be undertreated, warranting a
      reevaluation of current practice guidelines.

PMID- 25957437
TI  - Short-Term Smoking Cessation in English Resident Adults of Bangladeshi Origin: A
      Service Review.
AB  - INTRODUCTION: Cigarette smoking in English residents of Bangladeshi origin,
      particularly men, exceeds national estimates. Cessation outcomes and potential
      predictors of successful cigarette smoking cessation in this group await
      identification. METHODS: This service review reports cessation outcomes and
      predictors of success for 324 adult English resident Bangladeshi origin smokers
      recruited into a project providing a specialist tobacco cessation service.
      Interview measures included sociodemographics, tobacco use and dependence.
      Cessation data (self-reported and validated) at 4 weeks was also collected.
      Cessation rate and predictors of successful cessation, modeled using multiple
      logistic regressions, are reported. RESULTS: Clients' mean age was 45.59 (SD =
      13.83) years. Thirty-three (10%) were females. Mean level of small area
      deprivation was 56.98 (SD = 5.37). Initial mean expired air carbon monoxide score
      was 11.66 parts per million (SD = 7.17). Thirty-eight per cent used combination
      nicotine replacement therapy (NRT) with behavioral support. Sixty-nine percent
      reported successful smoking cessation after 4 weeks, validated with carbon
      monoxide (mean =1.23 parts per million, SD = 1.32). Predictors of successful
      cessation were use of combined NRT with behavioral support (OR = 1.82, 95% CI =
      1.07, 3.09), and community recruitment (OR = 1.85, 95% CI = 1.07, 3.22).
      CONCLUSIONS: English adult smokers of Bangladeshi origin resident in a highly
      disadvantaged locality, accessing community outreach services to help them quit
      and using NRT have validated short-term success rates greater than that
      locality's general population who access National Health Service Stop Smoking
      Services to quit.

PMID- 25957436
TI  - Severe malaria in children: A descriptive report from Kinshasa, the Democratic
      Republic of Congo.
AB  - The decline of susceptibility of Plasmodium falciparum to chloroquine and
      sulfadoxine-pyrimethamine resulted in the change of drug policy. This policy has
      probably changed the facies of the severe form of malaria. A prospective study
      was conducted in Kinshasa, the Democratic Republic of Congo. Data on children
      aged <=13 years, diagnosed with severe malaria were analyzed. In total, 378
      children were included with an overall median age of 8 years (age range: 1-13
      years). Dark urine was seen in 25.1% of cases. Metabolic acidosis (85.2%),
      hypoglycemia (62.2%) and hemoglobin <=5 g/dl (39.1%) were the common laboratories
      features. Severe malaria anemia, cerebral malaria and Blackwater fever (BWF) were
      found in 39.1, 30.1 and 25.4%, respectively. Mortality rate was 4%. BWF emerges
      as a frequent form of severe malaria in our midst. Availing artemisin-based
      combination treatments in the health care system is a priority to reduce the
      incidence of BWF in our environment. 

PMID- 25957438
TI  - Waterpipe Tobacco Smoking Prevalence and Correlates in 25 Eastern Mediterranean
      and Eastern European Countries: Cross-Sectional Analysis of the Global Youth
      Tobacco Survey.
AB  - INTRODUCTION: Waterpipe tobacco smoking is highly prevalent among young people in
      some settings. There is an absence of nationally representative prevalence
      studies of waterpipe tobacco use and dual use with other tobacco products in
      young people. METHODS: We conducted a secondary analysis of the Global Youth
      Tobacco Survey, a nationally representative cross-sectional study of students
      aged 13-15 years. Of 180 participating countries, 25 included optional waterpipe
      tobacco smoking questions: 15 Eastern Mediterranean and 10 Eastern European
      countries. We calculated the prevalence of current (past 30-day) waterpipe
      tobacco use, including dual waterpipe and other tobacco use, and used logistic
      regression models to identify sociodemographic correlates of waterpipe tobacco
      smoking. Individual country results were combined in a random effects meta
      analysis. RESULTS: Waterpipe tobacco smoking prevalence was highest in Lebanon
      (36.9%), the West Bank (32.7%) and parts of Eastern Europe (Latvia 22.7%, the
      Czech Republic 22.1%, Estonia 21.9%). These countries also recorded greater than
      10% prevalence of dual waterpipe and cigarette use. In a meta-analysis, higher
      odds of waterpipe tobacco smoking were found among males (Adjusted odds ratio
      [AOR] = 1.37, 95% confidence interval [CI] = 1.18% to 1.59%), cigarette users
      (AOR = 6.95, 95% CI = 5.74% to 8.42%), those whose parents (AOR = 1.54, 95% CI =
      1.31% to 1.82%) or peers smoked (AOR = 3.53, 95% CI = 2.97% to 4.20%) and those
      whose parents had higher educational attainment (Father, AOR = 1.47, 95% CI =
      1.14% to 1.89%; Mother, AOR = 1.62, 95% CI = 1.07% to 2.46%). We report on
      regional- and country income-level differences. CONCLUSIONS: Waterpipe tobacco
      smoking, including dual waterpipe and cigarette use, is alarmingly high in
      several Eastern Mediterranean and Eastern European countries. Ongoing waterpipe
      tobacco smoking surveillance is warranted.

PMID- 25957439
TI  - Ovarian reserve alterations in premenopausal women with chronic inflammatory
      rheumatic diseases: impact of rheumatoid arthritis, Behcet's disease and
      spondyloarthritis on anti-Mullerian hormone levels.
AB  - OBJECTIVE: Recent publications have shown a negative influence of SLE on female
      ovarian reserve. Other authors have not found a significant impact of Crohn's
      disease or early RA on anti-Mullerian hormone (AMH) levels. This study aimed to
      investigate the potential effect of Behcet's disease (BD), RA and SpA on ovarian
      reserve as reflected by serum AMH levels. METHODS: Serum samples from 33 RA, 32
      SpA and 30 BD patients without previous cytotoxic treatment were analysed and
      compared with age-matched, healthy controls. AMH was quantified using a standard
      ELISA with a standard value of 1-8 ng/ml; values <1 ng/ml defined a reduced
      ovarian reserve. RESULTS: Median age was 26, 28.5 and 33 years and median disease
      duration was 6, 5.9 and 7 years for RA, SpA and BD patients, respectively.
      Compared with healthy controls, patients had significantly reduced AMH levels,
      with a median value for RA of 1.8 ng/ml (control 2.4 ng/ml; P = 0.009), for SpA
      of 1.5 ng/ml (control 2.3 ng/ml; P = 0.013) and for BD of 1.1 ng/ml (control 1.9
      ng/ml; P = 0.007). HLA-B27 had a negative influence on ovarian reserve in SpA
      patients, whereas other serological parameters did not in the other diseases.
      CONCLUSION: This is the first study to show a reduced ovarian reserve in patients
      with RA, SpA or BD. Together with our findings in SLE, we conclude a negative
      influence of chronic rheumatic diseases on ovarian reserve.

PMID- 25957440
TI  - Development of the Sjogren's Syndrome Responder Index, a data-driven composite
      endpoint for assessing treatment efficacy.
AB  - OBJECTIVES: To determine which outcome measures detected rituximab efficacy in
      the Tolerance and Efficacy of Rituximab in Sjogren's Disease (TEARS) trial and to
      create a composite endpoint for future trials in primary SS (pSS). METHODS: Post
      hoc analysis of the multicentre randomized placebo-controlled double-blind TEARS
      trial. The results were validated using data from two other randomized controlled
      trials in pSS, assessing rituximab (single-centre trial in the Netherlands) and
      infliximab, respectively. RESULTS: Five outcome measures were improved by
      rituximab in the TEARS trial: patient-assessed visual analogue scale scores for
      fatigue, oral dryness and ocular dryness, unstimulated whole salivary flow and
      ESR. We combined these measures into a composite endpoint, the SS Responder Index
      (SSRI), and we defined an SSRI-30 response as a >=30% improvement in at least two
      of five outcome measures. In TEARS, the proportions of patients with an SSRI-30
      response in the rituximab and placebo groups at 6, 16 and 24 weeks were 47% vs
      21%, 50% vs 7% and 55% vs 20%, respectively (P < 0.01 for all comparisons). SSRI
      30 response rates after 12 and 24 weeks in the single-centre rituximab trial were
      68% (13/19) vs 40% (4/10) and 74% (14/19) vs 40% (4/10), respectively. No
      significant differences in SSRI-30 response rates were found between infliximab
      and placebo at any of the time points in the infliximab trial. CONCLUSION: A core
      set of outcome measures used in combination suggests that rituximab could be
      effective and infliximab ineffective in pSS. The SSRI might prove useful as the
      primary outcome measure for future therapeutic trials in pSS.

PMID- 25957441
TI  - A case of relapsing neurosarcoidosis with brain nodules and hydrocephalus
      successfully treated by corticosteroid and methotrexate.

PMID- 25957442
TI  - Colorectal cancer: to stack or sequence therapy?

PMID- 25957443
TI  - Doug Lowy becomes acting director of National Cancer Institute.

PMID- 25957444
TI  - Programmed death protein 1 inhibitors making inroads in multiple cancers.

PMID- 25957447
TI  - Understanding random cancers.

PMID- 25957452
TI  - Weekend emergency   admissions and mortality   in England and Wales.

PMID- 25957453
TI  - Aligning incentives to fulfil the promise of personalised medicine.

PMID- 25957456
TI  - The hepatic buttress: A novel surgical technique to treat an intrapericardial
      diaphragmatic defect after hybrid myocardial ablation.

PMID- 25957454
TI  - Subclinical seizures identified by postoperative electroencephalographic
      monitoring are common after neonatal cardiac surgery.
AB  - OBJECTIVES: The American Clinical Neurophysiology Society recommends continuous
      electroencephalographic monitoring after neonatal cardiac surgery because
      seizures are common, often subclinical, and associated with worse neurocognitive
      outcomes. We performed a quality improvement project to monitor for postoperative
      seizures in neonates with congenital heart disease after surgery with
      cardiopulmonary bypass. METHODS: We implemented routine continuous
      electroencephalographic monitoring and reviewed the results for an 18-month
      period. Clinical data were collected by chart review, and continuous
      electroencephalographic tracings were interpreted using standardized American
      Clinical Neurophysiology Society terminology. Electrographic seizures were
      classified as electroencephalogram-only or electroclinical seizures. Multiple
      logistic regression was used to assess associations between seizures and
      potential clinical and electroencephalogram predictors. RESULTS: A total of 161
      of 172 eligible neonates (94%) underwent continuous electroencephalographic
      monitoring. Electrographic seizures occurred in 13 neonates (8%) beginning at a
      median of 20 hours after return to the intensive care unit after surgery.
      Neonates with all types of congenital heart disease had seizures. Seizures were
      electroencephalogram only in 11 neonates (85%). Status epilepticus occurred in 8
      neonates (62%). In separate multivariate models, delayed sternal closure or
      longer deep hypothermic circulatory arrest duration was associated with an
      increased risk for seizures. Mortality was higher among neonates with than
      without seizures (38% vs 3%, P < .001). CONCLUSIONS: Continuous
      electroencephalographic monitoring identified seizures in 8% of neonates after
      cardiac surgery with cardiopulmonary bypass. The majority of seizures had no
      clinical correlate and would not have been otherwise identified. Seizure
      occurrence is a marker of greater illness severity and increased mortality.
      Further study is needed to determine whether seizure identification and
      management lead to improved outcomes.

PMID- 25957457
TI  - [Surgery for pancreatic cancer: Evidence-based surgical strategies].
AB  - Pancreatic cancer surgery represents a challenge for surgeons due to its
      technical complexity, the potential complications that may appear, and ultimately
      because of its poor survival. The aim of this article is to summarize the
      scientific evidence regarding the surgical treatment of pancreatic cancer in
      order to help surgeons in the decision making process in the management of these
      patients .Here we will review such fundamental issues as the need for a biopsy
      before surgery, the type of pancreatic anastomosis leading to better results, and
      the need for placement of drains after pancreatic surgery will be discussed. 

PMID- 25957458
TI  - Molecular diagnosis of toxoplasmosis: value of the buffy coat for the detection
      of circulating Toxoplasma gondii.
AB  - Early detection of Toxoplasma tachyzoites circulating in blood using PCR is
      recommended for immunosuppressed patients at high risk for disseminated
      toxoplasmosis. Using a toxoplasmosis mouse model, we show that the sensitivity of
      detection is higher using buffy coat isolated from a large blood volume than
      using whole blood for this molecular monitoring. 

PMID- 25957460
TI  - Review of Non-Bacterial Infections in Respiratory Medicine: Viral Pneumonia.
AB  - Although bacteria are the main pathogens involved in community-acquired
      pneumonia, a significant number of community-acquired pneumonia are caused by
      viruses, either directly or as part of a co-infection. The clinical picture of
      these different pneumonias can be very similar, but viral infection is more
      common in the pediatric and geriatric populations, leukocytes are not generally
      elevated, fever is variable, and upper respiratory tract symptoms often occur;
      procalcitonin levels are not generally affected. For years, the diagnosis of
      viral pneumonia was based on cell culture and antigen detection, but since the
      introduction of polymerase chain reaction techniques in the clinical setting,
      identification of these pathogens has increased and new microorganisms such as
      human bocavirus have been discovered. In general, influenza virus type A and
      syncytial respiratory virus are still the main pathogens involved in this entity.
      However, in recent years, outbreaks of deadly coronavirus and zoonotic influenza
      virus have demonstrated the need for constant alert in the face of new emerging
      pathogens. Neuraminidase inhibitors for viral pneumonia have been shown to reduce
      transmission in cases of exposure and to improve the clinical progress of
      patients in intensive care; their use in common infections is not recommended.
      Ribavirin has been used in children with syncytial respiratory virus, and in
      immunosuppressed subjects. Apart from these drugs, no antiviral has been shown to
      be effective. Prevention with anti-influenza virus vaccination and with
      monoclonal antibodies, in the case of syncytial respiratory virus, may reduce the
      incidence of pneumonia. 

PMID- 25957459
TI  - Novel culture medium for the axenic growth of Balamuthia mandrillaris.
AB  - Until now, for axenic cultivation of Balamuthia mandrillaris, the BM-3 culture
      medium and the Modified Chang's special medium have been the only ones
      recommended, but they have some disadvantages, as both require many components
      and their preparations are laborious. Therefore, we developed a novel culture
      medium for B. mandrillaris axenic cultivation. Each one of the 11 components of
      BM-3 was combined with Cerva's medium as basal culture medium. Ten strains of B.
      mandrillaris including the reference strain CDC:V039 and 9 environmental isolates
      were used during trials. After testing all combinations, the basal medium
      complemented with 10* Hank's balanced salt solution was the only one that
      supported confluent growth of B. mandrillaris. Cell shape and motility of
      trophozoites were normal. This developed medium is as useful as BM-3 for
      axenization. The development of a cheaper and easy-to-prepare medium for B.
      mandrillaris opens the possibility of increasing its study. 

PMID- 25957461
TI  - The use of poetry writing in nurse education: An evaluation.
AB  - BACKGROUND: Arts based approaches have been used in health education in various
      ways e.g. to develop emotional awareness, reduce anxiety and stress and assess
      communication skills. OBJECTIVES: This evaluation aimed to explore the use of
      poetry writing as a way for undergraduate nursing students to consider their
      feelings about important practice issues. METHODS: 42 first year undergraduate
      nursing students were asked to write a poem which focussed on an important
      nursing issue e.g. compassion, communication or the therapeutic role of the
      nurse. They were then asked to read the poem aloud to a small group and discuss
      its meaning. RESULTS: 60% (n=24) of students reported that the exercise had
      increased understanding of their chosen subject, 75% (n=30) stated that they had
      learned something about themselves and 65% (n=26) of students stated that they
      had enjoyed the poetry writing exercise. Qualitative comments suggested that the
      use of poetry enabled greater understanding of others' experiences, promoted open
      and honest reflection on feelings and supported the development of confidence.
      CONCLUSION: There is a need for teaching methods which engage and develop
      students' imagination, if they are going to be adequately prepared for the
      demands of nursing practice. Poetry writing and discussion supports the
      development of confidence, therapeutic communication skills and the ability to
      think creatively.

PMID- 25957462
TI  - Different ECG manifestations of left ventricular hypertrophy in presence of
      intermittent LBBB and RBBB.
AB  - An 86-year-old female with aortic stenosis was qualified for invasive correction
      of the valvular heart disease. She developed a severe ventricular hypertrophy
      (LVH) and had an intermittent left bundle branch block (LBBB) and right bundle
      branch block (RBBB). We report the case of a single electrocardiographic
      examination showing changes specific for LVH, present in all forms of
      intraventricular conduction. The case perfectly depicts how the intracardiac
      vectors of depolarization change due to bundle branch blocks and how it effects
      QRS complex morphology. 

PMID- 25957464
TI  - Prediction of ultrasonic pulse velocity for enhanced peat bricks using adaptive
      neuro-fuzzy methodology.
AB  - Ultrasonic pulse velocity is affected by defects in material structure. This
      study applied soft computing techniques to predict the ultrasonic pulse velocity
      for various peats and cement content mixtures for several curing periods. First,
      this investigation constructed a process to simulate the ultrasonic pulse
      velocity with adaptive neuro-fuzzy inference system. Then, an ANFIS network with
      neurons was developed. The input and output layers consisted of four and one
      neurons, respectively. The four inputs were cement, peat, sand content (%) and
      curing period (days). The simulation results showed efficient performance of the
      proposed system. The ANFIS and experimental results were compared through the
      coefficient of determination and root-mean-square error. In conclusion, use of
      ANFIS network enhances prediction and generation of strength. The simulation
      results confirmed the effectiveness of the suggested strategies. 

PMID- 25957463
TI  - ERbeta induces the differentiation of cultured osteoblasts by both Wnt/beta
      catenin signaling pathway and estrogen signaling pathways.
AB  - Although 17beta-estradial (E2) is known to stimulate bone formation, the
      underlying mechanisms are not fully understood. Recent studies have implicated
      the Wnt/beta-catenin pathway as a major signaling cascade in bone biology. The
      interactions between Wnt/beta-catenin signaling pathway and estrogen signaling
      pathways have been reported in many tissues. In this study, E2 significantly
      increased the expression of beta-catenin by inducing phosphorylations of GSK3beta
      at serine 9. ERbeta siRNAs were transfected into MC3T3-E1 cells and revealed that
      ERbeta involved E2-induced osteoblasts proliferation and differentiation via
      Wnt/beta-catenin signaling. The osteoblast differentiation genes (BGP, ALP and
      OPN) and proliferation related gene (cyclin D1) expression were significantly
      induced by E2-mediated ERbeta. Furthermore immunofluorescence and
      immunoprecipitation analysis demonstrated that E2 induced the accumulation of
      beta-catenin protein in the nucleus which leads to interaction with T-cell
      specific transcription factor/lymphoid enhancer binding factor (TCF/LEF)
      transcription factors. Taken together, these findings suggest that E2 promotes
      osteoblastic proliferation and differentiation by inducing proliferation-related
      and differentiation-related gene expression via ERbeta/GSK-3beta-dependent
      Wnt/beta-catenin signaling pathway. Our findings provide novel insights into the
      mechanisms of action of E2 in osteoblastogenesis. 

PMID- 25957465
TI  - Endocan-1 concentrations in maternal and fetal plasma and placentae in pre
      eclampsia in the third trimester of pregnancy.
AB  - INTRODUCTION: Endocan-1 has been proposed as a possible biomarker and predictor
      of vascular endothelial related pathologies. Thus, we hypothesised that Endocan-1
      levels would be up-regulated in maternal plasma and placentae from women with pre
      eclampsia. The aim of our study was to compare Endocan-1 concentrations in
      maternal/fetal plasma and placentae from normotensive and pre-eclamptic
      pregnancies. METHODS: Observational and case-controlled study, at the Sao Lucas
      Hospital, Brazil. Placental biopsies, maternal/umbilical venous (fetal) plasma
      were taken from 67 normotensive and 50 pre-eclamptic women. Endocan-1 levels were
      quantified using MagPlex(TH)-C and analysed by Analysis of Covariance and Pearson
      correlation. The null hypothesis was rejected at p<0.05. RESULTS: Higher levels
      of Endocan-1 were found in maternal plasma in the pre-eclamptic group (mean
      ratio=1.49; 95% confidence interval: 1.19-1.85, p=0.001), with a moderate effect
      size (Cohen's D=0.84). Placental Endocan-1 levels (MUg/g) were lower in pre
      eclampsia (1.52 [1.10, 2.40] vs. 2.24 [1.32, 3.75], p=0.033) and fetal Endocan-1
      concentration (ng/ml) did not show any difference between groups (3.10 [2.60,
      4.54] vs. 2.91 [2.20, 3.66] p=0.085). In addition, an up-regulation of maternal
      plasma Endocan-1 in the pre-eclamptic group was observed when stratified in
      relation to gestational age, systolic blood pressure and proteinuria (p<0.05, for
      all). Furthermore, a positive correlation between Endocan-1 concentration in
      maternal vs. fetal plasma was also found (r=0.258, p=0.015). For the matched
      samples, a negative correlation between Endocan-1 in maternal/fetal plasma with
      birthweights, placental weights and gestational age at delivery was observed
      (p<0.05 for all). DISCUSSION: Endocan-1 is increased in women with pre-eclampsia
      for all strata, which highlight the importance of this molecule as a possible
      biomarker. The negative correlations between Endocan-1 and clinical data suggest
      that this molecule may also be involved with prematurity and low birth weight,
      which warrants further investigations.

PMID- 25957467
TI  - Circulating microRNAs for the prediction of metastasis in breast cancer patients
      diagnosed with early stage disease.
AB  - Breast cancer is the second most common malignancy diagnosed in women worldwide.
      The greatest cause of breast cancer mortality is development of metastasis. For
      many women metastasis is an early event in breast cancer which goes undetected
      until its presentation, thus there is an urgent need for the development of
      biomarkers to predict those patients at greatest risk. The expression of a group
      of small non-coding RNAs, termed microRNAs, has been shown to be altered in
      tumours. Furthermore, microRNAs identified as being highly expressed in breast
      cancer tumours can also be detected in the circulation. Circulating microRNAs are
      an emerging field of biomarker research which have the benefit of being able to
      be obtained non-invasively and analysed rapidly and relatively cheaply. Here the
      potential use of circulating miRNAs to detect metastasis in discussed and the
      current barriers to their progression to the clinic. 

PMID- 25957466
TI  - Compartmentalization of acute phase reactants Interleukin-6, C-Reactive Protein
      and Procalcitonin as biomarkers of intra-amniotic infection and chorioamnionitis.
AB  - BACKGROUND: The arsenal of maternal and amniotic fluid (AF) immune response to
      local or systemic infection includes among others the acute-phase reactants IL-6,
      C-Reactive Protein (CRP) and Procalcitonin (PCT). If these molecules can be used
      as non-invasive biomarkers of intra-amniotic infection (IAI) in the subclinical
      phase of the disease remains incompletely known. METHODS: We used time-matched
      maternal serum, urine and AF from 100 pregnant women who had an amniocentesis to
      rule out IAI in the setting of preterm labor, PPROM or systemic inflammatory
      response (SIR: pyelonephritis, appendicitis, pneumonia) to infection. Cord blood
      was analyzed in a subgroup of cases. We used sensitive immunoassays to quantify
      the levels of inflammatory markers in the maternal blood, urine and AF
      compartment. Microbiological testing and placental pathology was used to
      establish infection and histological chorioamnionitis. RESULTS: PCT was not a
      useful biomarker of IAI in any of the studied compartments. Maternal blood IL-6
      and CRP levels were elevated in women with subclinical IAI. Compared to
      clinically manifest chorioamnionitis group, women with SIR have higher maternal
      blood IL-6 levels rendering some marginal diagnostic benefit for this condition.
      Urine was not a useful biological sample for assessment of IAI using either of
      these three inflammatory biomarkers. CONCLUSIONS: In women with subclinical IAI,
      the large overlapping confidence intervals and different cut-offs for the
      maternal blood levels of IL-6, CRP and PCT likely make interpretation of their
      absolute values difficult for clinical decision-making.

PMID- 25957468
TI  - Testing in Microbiome-Profiling Studies with MiRKAT, the Microbiome Regression
      Based Kernel Association Test.
AB  - High-throughput sequencing technology has enabled population-based studies of the
      role of the human microbiome in disease etiology and exposure response. Distance
      based analysis is a popular strategy for evaluating the overall association
      between microbiome diversity and outcome, wherein the phylogenetic distance
      between individuals' microbiome profiles is computed and tested for association
      via permutation. Despite their practical popularity, distance-based approaches
      suffer from important challenges, especially in selecting the best distance and
      extending the methods to alternative outcomes, such as survival outcomes. We
      propose the microbiome regression-based kernel association test (MiRKAT), which
      directly regresses the outcome on the microbiome profiles via the semi-parametric
      kernel machine regression framework. MiRKAT allows for easy covariate adjustment
      and extension to alternative outcomes while non-parametrically modeling the
      microbiome through a kernel that incorporates phylogenetic distance. It uses a
      variance-component score statistic to test for the association with analytical p
      value calculation. The model also allows simultaneous examination of multiple
      distances, alleviating the problem of choosing the best distance. Our simulations
      demonstrated that MiRKAT provides correctly controlled type I error and adequate
      power in detecting overall association. "Optimal" MiRKAT, which considers
      multiple candidate distances, is robust in that it suffers from little power loss
      in comparison to when the best distance is used and can achieve tremendous power
      gain in comparison to when a poor distance is chosen. Finally, we applied MiRKAT
      to real microbiome datasets to show that microbial communities are associated
      with smoking and with fecal protease levels after confounders are controlled for.

PMID- 25957470
TI  - [Renal involvement in glycogen storage disease type 1: Practical issues].
AB  - AIM: To investigate risk factors of renal complications in glycogen storage
      disease type I, in order to identify practical implications for renal
      preservation. METHODS: A retrospective study of 38 patients with glycogen storage
      disease type I. RESULTS: The patients studied were 8.6 years old in average (1.5
      to 22 years) and were followed during 7.4 +/- 4.5 years. Hypercalciuria was
      detected in 23 patients and was related to acidosis (P=0.028), higher lactate
      levels (5.9 +/- 3.5 versus 3.7 +/- 1.7 mmol/L; P=0.013) and smaller height (-2.1
      +/- 1.5 SD versus -0.8 +/- 1.5 SD; P=0.026). Urolithiasis was diagnosed in 7
      cases. Glomerular disease (19/38) was more frequent in cases with severe
      hypertriglyceridemia (P=0.042) and occurred at an older age (P=0.007).
      Microalbuminuria occurred in 15/31 cases; ACE inhibitors were prescribed in only
      8 cases. The frequency of renal complications did not differ according to the
      diet group (continuous enteral feeding or uncooked starch). Logistic regression
      concluded as risk factors: lactic acidosis for tubular disease and age>10 years
      for glomerular disease. CONCLUSIONS: Renal involvement is common in glycogen
      storage disease type I patients. Tubular abnormalities are precocious, related to
      lactic acidosis and may be detected by monitoring of urinary calcium. Glomerular
      hyperfiltration is the first stage of a progressive glomerular disease and is
      related to age. Practical implications for renal preservation are discussed based
      on our results and literature.

PMID- 25957471
TI  - Crystal structure of Cry51Aa1: A potential novel insecticidal aerolysin-type beta
      pore-forming toxin from Bacillus thuringiensis.
AB  - The structures of several Bacillus thuringiensis (Bt) insecticidal crystal
      proteins have been determined by crystallographic methods and a close
      relationship has been explicated between specific toxicities and conserved three
      dimensional architectures. In this study, as a representative of the coleopteran-
      and hemipteran-specific Cry51A group, the complete structure of Cry51Aa1 protoxin
      has been determined by X-ray crystallography at 1.65 A resolution. This is the
      first report of a coleopteran-active Bt insecticidal toxin with high structural
      similarity to the aerolysin-type beta-pore forming toxins (beta-PFTs). Moreover,
      study of featured residues and structural elements reveal their possible roles in
      receptor binding and pore formation events. This study provides new insights into
      the action of aerolysin-type beta-PFTs from a structural perspective, and could
      be useful for the control of coleopteran and hemipteran insect pests in
      agricultures. 

PMID- 25957472
TI  - Immunogenicity characterization of the multi-epitope vaccine CTB-UE with chitosan
      CpG as combination adjuvants against Helicobacter pylori.
AB  - Urease is considered as an excellent vaccine candidate antigen against
      Helicobacter pylori (H. pylori) infection. Our previous study reported a novel
      multi-epitope vaccine CTB-UE which was composed of the mucosal adjuvant cholera
      toxin B subunit (CTB) and five cell epitopes from urease subunits. Murine
      experiments indicated that it could induce cellular and humoral immune responses
      intensively and attenuate H. pylori infection effectively in mice model. However,
      the body expression and lack of suitable adjuvant of this epitope vaccine
      restricted its application. In this study, new recombinant Escherichia coli
      strains was established to increase the solubility by fusing thioredoxin (Trx)
      and the combination adjuvants which composed of the chitosan and CpG were adopted
      to enhance the immunogenicity of CTB-UE for oral immunization. The experimental
      results indicated that the levels of IgG2a, IgG1 and IgA in the serum and the
      levels of sIgA in stomach, intestine and feces were significantly higher in the
      vaccinated group compared with the model control group. Additionally, chitosan
      CpG combination adjuvants changed the ratio of IgG2a/IgG1 and conferred Th1/Th17
      mediated protective immune responses. These results demonstrate that the oral
      vaccine with chitosan-CpG as combination adjuvants may be a promising vaccine
      candidate against H. pylori infection. 

PMID- 25957473
TI  - Regulation of the ryanodine receptor by anti-apoptotic Bcl-2 is independent of
      its BH3-domain-binding properties.
AB  - The regulation of intracellular Ca(2+) signaling is an important aspect of how
      anti-apoptotic B-cell lymphoma 2 (Bcl-2) proteins regulate cell death and cell
      survival. At the endoplasmic reticulum (ER) the Bcl-2 homology (BH) 4 domain of
      Bcl-2 is known to bind to and inhibit both inositol 1,4,5-trisphosphate receptors
      (IP3Rs) and ryanodine receptors (RyRs). Besides this, drugs that target the
      hydrophobic cleft of Bcl-2 have been reported to deplete ER Ca(2+) stores in an
      IP3R- and RyR-dependent way. This suggests that the hydrophobic cleft of Bcl-2
      may also be involved in regulating these ER-located Ca(2+)-release channels.
      However, the contribution of the hydrophobic cleft on the binding and regulatory
      properties of Bcl-2 to either IP3Rs or RyRs has until now not been studied. Here,
      the importance of the hydrophobic cleft of Bcl-2 in binding to and inhibiting the
      RyR was assessed by using a genetic approach based on site-directed mutagenesis
      of Bcl-2's hydrophobic cleft and a pharmacological approach based on the
      selective Bcl-2 hydrophobic cleft inhibitor, ABT-199. Both binding assays and
      single-cell Ca(2+) measurements indicated that RyR binding and the inhibition of
      RyR-mediated Ca(2+) release by Bcl-2 is independent of its hydrophobic cleft. 

PMID- 25957469
TI  - Autosomal-Dominant Multiple Pterygium Syndrome Is Caused by Mutations in MYH3.
AB  - Multiple pterygium syndrome (MPS) is a phenotypically and genetically
      heterogeneous group of rare Mendelian conditions characterized by multiple
      pterygia, scoliosis, and congenital contractures of the limbs. MPS typically
      segregates as an autosomal-recessive disorder, but rare instances of autosomal
      dominant transmission have been reported. Whereas several mutations causing
      recessive MPS have been identified, the genetic basis of dominant MPS remains
      unknown. We identified four families affected by dominantly transmitted MPS
      characterized by pterygia, camptodactyly of the hands, vertebral fusions, and
      scoliosis. Exome sequencing identified predicted protein-altering mutations in
      embryonic myosin heavy chain (MYH3) in three families. MYH3 mutations underlie
      distal arthrogryposis types 1, 2A, and 2B, but all mutations reported to date
      occur in the head and neck domains. In contrast, two of the mutations found to
      cause MPS in this study occurred in the tail domain. The phenotypic overlap among
      persons with MPS, coupled with physical findings distinct from other conditions
      caused by mutations in MYH3, suggests that the developmental mechanism underlying
      MPS differs from that of other conditions and/or that certain functions of
      embryonic myosin might be perturbed by disruption of specific residues and/or
      domains. Moreover, the vertebral fusions in persons with MPS, coupled with
      evidence of MYH3 expression in bone, suggest that embryonic myosin plays a role
      in skeletal development.

PMID- 25957474
TI  - Hypomyelinating leukodystrophy-associated missense mutation in HSPD1 blunts
      mitochondrial dynamics.
AB  - Myelin-forming glial cells undergo dynamic morphological changes in order to
      produce mature myelin sheaths with multiple layers. In the central nervous system
      (CNS), oligodendrocytes differentiate to insulate neuronal axons with myelin
      sheaths. Myelin sheaths play a key role in homeostasis of the nervous system, but
      their related disorders lead not only to dismyelination and repeated
      demyelination but also to severe neuropathies. Hereditary hypomyelinating
      leukodystrophies (HLDs) are a group of such diseases affecting oligodendrocytes
      and are often caused by missense mutations of the respective responsible genes.
      Despite increasing identification of gene mutations through advanced nucleotide
      sequencing technology, studies on the relationships between gene mutations and
      their effects on cellular and subcellular aberrance have not followed at the same
      rapid pace. In this study, we report that an HLD4-associated (Asp-29-to-Gly)
      mutant of mitochondrial heat shock 60-kDa protein 1 (HSPD1) causes short-length
      morphologies and increases the numbers of mitochondria due to their aberrant
      fission and fusion cycles. In experiments using a fluorescent dye probe, this
      mutation decreases the mitochondrial membrane potential. Also, mitochondria
      accumulate in perinuclear regions. HLD4-associated HSPD1 mutant blunts
      mitochondrial dynamics, probably resulting in oligodendrocyte malfunction. This
      study constitutes a first finding concerning the relationship between disease
      associated HSPD1 mutation and mitochondrial dynamics, which may be similar to the
      relationship between another disease-associated HSPD1 mutation (MitCHAP-60
      disease) and aberrant mitochondrial dynamics. 

PMID- 25957475
TI  - Motilin stimulates pepsinogen secretion in Suncus murinus.
AB  - Motilin and ghrelin are gastrointestinal hormones that stimulate the migrating
      motor complex (MMC) of gastrointestinal motility during the fasting state. In
      this study, we examined the effect of motilin and ghrelin on pepsinogen secretion
      in anesthetized suncus (house musk shrew, Suncus murinus), a ghrelin- and motilin
      producing mammal. By using a gastric lumen-perfusion system, we found that the
      intravenous administration of carbachol and motilin stimulated pepsinogen
      secretion, the latter in a dose-dependent manner, whereas ghrelin had no effect.
      We then investigated the pathways of motilin-induced pepsinogen secretion using
      acetylcholine receptor antagonists. Treatment with atropine, a muscarinic
      acetylcholine receptor antagonist, completely inhibited both carbachol and
      motilin-induced pepsinogen secretion. Motilin-induced pepsinogen secretion was
      observed in the vagotomized suncus. This is the first report demonstrating that
      motilin stimulates pepsinogen secretion, and suggest that this effect occurs
      through a cholinergic pathway in suncus. 

PMID- 25957476
TI  - Enhancement of the FGFR1 signaling in the FGFR1-5-HT1A heteroreceptor complex in
      midbrain raphe 5-HT neuron systems. Relevance for neuroplasticity and depression.
AB  - New findings show existence of FGFR1-5-HT1A heteroreceptor complexes in 5-HT
      nerve cells of the dorsal and median raphe nuclei of the rat midbrain and
      hippocampus. Synergistic receptor-receptor interactions in these receptor
      complexes indicated their enhancing role in hippocampal plasticity. The existence
      of FGFR1-5-HT1A heteroreceptor complexes also in midbrain raphe 5-HT nerve cells
      open up the possibility that antidepressant drugs by increasing extracellular 5
      HT levels can cause an activation of the FGF-2/FGFR1 mechanism in these nerve
      cells as well. Therefore, the agonist modulation of the FGFR1-5-HT1A
      heteroreceptor complexes and their specific role is now determined in rat
      medullary raphe RN33B cells and in the caudal midline raphe area of the midbrain
      rich in 5-HT nerve cells. The combined i.c.v. treatment with FGF-2 and the 5-HT1A
      agonist 8-OHDPAT synergistically increased FGFR1 and ERK1/2 phosphorylation in
      the raphe midline area of the midbrain and in the RN33B cells. Cotreatment with
      FGF2 and the 5-HT1A agonist induced RN33B cell differentiation as seen from
      development of an increased number and length of extensions per cell and their
      increased 5-HT immunoreactivity. These signaling and differentiation events were
      dependent on the receptor interface since they were blocked by incubation with
      TMV but not by TMII of the 5-HT1A receptor. Taken together, the 5-HT1A
      autoreceptors by being part of a FGFR1-5-HT1A heteroreceptor complex in the
      midbrain raphe 5-HT nerve cells appears to have also a trophic role in the
      central 5-HT neuron systems besides playing a key role in reducing the firing of
      these neurons. 

PMID- 25957477
TI  - Endoscopic radial incision and cutting procedure for a colorectal anastomotic
      stricture.

PMID- 25957479
TI  - Fake out: a giant fibroepithelial polyp mimicking a rectal tumor.

PMID- 25957478
TI  - Endoscopy/EUS-guided fiducial marker placement in patients with esophageal
      cancer: a comparative analysis of 3 types of markers.
AB  - BACKGROUND: Markers placed at the borders of esophageal tumors are potentially
      useful to facilitate radiotherapy (RT) target delineation, which offers the
      possibility of image-guided RT. OBJECTIVE: To evaluate and compare the
      feasibility and technical benefit of endoscopy/EUS-guided marker placement of 3
      different types of markers in patients with esophageal cancer referred for RT.
      DESIGN: Prospective, single-center, feasibility and comparative study. SETTING:
      Tertiary-care medical center. PATIENTS: Thirty patients with esophageal cancer
      who were referred for RT. INTERVENTIONS: Patients underwent endoscopy/EUS-guided
      implantation of 1 type of marker. A solid gold marker (SM) with fixed dimensions,
      a flexible coil-shaped gold marker (FM) with hand-cut length (2-10 mm), and a
      radiopaque hydrogel marker (HG) were used. Technical feasibility and adverse
      events were registered. CT scans and cone-beam CT scans (CBCT) acquired during RT
      were analyzed to determine and compare the visibility and continuous clear
      visibility of the implanted markers. MAIN OUTCOME MEASUREMENTS: Technical
      feasibility, technical benefit, and adverse events of 3 types of markers.
      RESULTS: A total of 101 markers were placed in 30 patients. Implantation was
      technically feasible in all patients without grade 3 to 4 adverse events. Two
      patients with asymptomatic mediastinitis and one with asymptomatic pneumothorax
      were seen. Visibility on CT scan of all 3 types of implanted markers was adequate
      for target delineation. Eighty percent of FMs remained continuously visible over
      the treatment period on CBCT, significantly better than SMs (63%) and HGs (11%)
      (P = .015). When we selected FMs >=5 mm, 90.5% remained visible on CBCT between
      implantation and the end of RT. LIMITATIONS: Single-center, nonrandomized design.
      CONCLUSION: Endoscopy/EUS-guided fiducial marker placement for esophageal cancer
      is both safe and feasible and can be used for target volume delineation purposes
      on CT. Our results imply a significant advantage of FMs over SMs and HGs,
      regarding visibility and continuous clear visibility over the treatment period. (
      CLINICAL TRIAL REGISTRATION NUMBER: NTR4724.).

PMID- 25957480
TI  - Theme Series--UPR in cancer.

PMID- 25957481
TI  - Therapeutic values, chemical constituents and toxicity of Taiwanese Dysosma
      pleiantha--a review.
AB  - Dysosma pleiantha (Hance) Woodson also called as Bajiaolian belongs to the family
      Berberidaceae, is widely used in Taiwan as traditional Chinese herbal medicine
      for more than thousands of years. It is usually recommended by various
      traditional Chinese medical doctors and herbal pharmacies for general remedies
      including postpartum recovery, treatment of weakness, neck mass, acne, hepatoma,
      lumbago, snakebite, tumor growth and dysmenorrhea. In the textbooks of
      traditional Chinese medicine, there is limited information about the toxicity of
      Bajiaolian. Podophyllotoxin, a lignan is the main toxic ingredient of Bajiaolian
      rhizome. Therefore, Bajiaolian is documented as the fifth highest cause of
      poisoning among the herbal medicine in Taiwan. Since the therapeutic and toxic
      doses are very close, Bajiaolian poisoning cases are frequently reported in
      Taiwan. Moreover, Dysosma poisoning cases are difficult to diagnosis because
      physicians are unfamiliar with this medicine's multiple clinical presentations in
      different stages of intoxication. Therefore, the objective of this review is to
      represent the collective information available in literatures regarding D.
      pleiantha, a cytotoxic lignan containing medicinal plant. Specifically, the
      literatures have been reviewed for articles pertaining to chemical constituents,
      properties, therapeutical benefits, toxicity, poisoning symptoms, toxic as well
      as therapeutic dose and medical management.

PMID- 25957482
TI  - Basement membrane protein nidogen-1 is a target of meprin beta in cisplatin
      nephrotoxicity.
AB  - Meprins are oligomeric metalloproteinases that are abundantly expressed in the
      brush-border membranes of renal proximal tubules. During acute kidney injury
      (AKI) induced by cisplatin or ischemia-reperfusion, membrane-bound meprins are
      shed and their localization is altered from the apical membranes toward the
      basolateral surface of the proximal tubules. Meprins are capable of cleaving
      basement membrane proteins in vitro, however, it is not known whether meprins are
      able to degrade extracellular matrix proteins under pathophysiological conditions
      in vivo. The present study demonstrates that a basement membrane protein, nidogen
      1, is cleaved and excreted in the urine of mice subjected to cisplatin-induced
      nephrotoxicity, a model of AKI. Cleaved nidogen-1 was not detected in the urine
      of untreated mice, but during the progression of cisplatin nephrotoxicity, the
      excretion of cleaved nidogen-1 increased in a time-dependent manner. The meprin
      inhibitor actinonin markedly prevented urinary excretion of the cleaved nidogen
      1. In addition, meprin beta-deficient mice, but not meprin alpha-deficient mice,
      subjected to cisplatin nephrotoxicity significantly suppressed excretion of
      cleaved nidogen-1, further suggesting that meprin beta is involved in the
      cleavage of nidogen-1. These studies provide strong evidence for a
      pathophysiological link between meprin beta and urinary excretion of cleaved
      nidogen-1 during cisplatin-induced AKI.

PMID- 25957483
TI  - Enzyme activity and gene expression profiles of Xanthobacter autotrophicus GJ10
      during aerobic biodegradation of 1,2-dichloroethane.
AB  - Xanthobacter autotrophicus GJ10 has been widely studied because of its ability to
      degrade halogenated compounds, especially 1,2-dichloroethane (1,2-DCA), which is
      achieved through chromosomal as well as plasmid pAUX1 encoded 1,2-DCA degrading
      genes. This work described the gene expression and enzyme activity profiles as
      well as the intermediates formed during the 1,2-DCA degradation by this organism.
      A correlation between gene expression, enzyme activity and metabolic
      intermediates, after the induction of GJ10 grown culture with 1,2-DCA, was
      established at different time intervals. Haloalkane dehalogenase (dhlA) and
      haloacid dehalogenase (dhlB) were constitutively expressed while the expression
      of alcohol dehydrogenase (max) and aldehyde dehydrogenase (ald) was found to be
      inducible. The DhlA and DhlB activities were relatively higher compared to that
      of the inducible enzymes, Max and Ald. To the best of our knowledge, this is the
      first study to correlate gene expression profiles with enzyme activity and
      metabolite formation during 1,2-DCA degradation process in GJ10. Findings from
      this study may assist in fully understanding the mechanism of 1,2-DCA degradation
      by GJ10. It could also assist in the design and implementation of appropriate
      bioaugmentation strategies for complete removal of 1,2-DCA from contaminated
      environment. 

PMID- 25957484
TI  - Neurobiology of insight deficits in schizophrenia: An fMRI study.
AB  - Prior research has shown insight deficits in schizophrenia to be associated with
      specific neuroimaging changes (primarily structural) especially in the prefrontal
      sub-regions. However, little is known about the functional correlates of impaired
      insight. Seventeen patients with schizophrenia (mean age 40.0+/-10.3; M/F=14/3)
      underwent fMRI on a Philips 3.0 T Achieva system while performing on a self
      awareness task containing self- vs. other-directed sentence stimuli. SPM5 was
      used to process the imaging data. Preprocessing consisted of realignment,
      coregistration, and normalization, and smoothing. A regression analysis was used
      to examine the relationship between brain activation in response to self-directed
      versus other-directed sentence stimuli and average scores on behavioral measures
      of awareness of symptoms and attribution of symptoms to the illness from Scale to
      Assess Unawareness of Mental Disorders. Family Wise Error correction was employed
      in the fMRI analysis. Average scores on awareness of symptoms (1=aware;
      5=unaware) were associated with activation of multiple brain regions, including
      prefrontal, parietal and limbic areas as well as basal ganglia. However, average
      scores on correct attribution of symptoms (1=attribute; 5=misattribute) were
      associated with relatively more localized activation of prefrontal cortex and
      basal ganglia. These findings suggest that unawareness and misattribution of
      symptoms may have different neurobiological basis in schizophrenia. While symptom
      unawareness may be a function of a more complex brain network, symptom
      misattribution may be mediated by specific brain regions. 

PMID- 25957485
TI  - Clozapine potentiation of GABA mediated cortical inhibition in treatment
      resistant schizophrenia.
AB  - BACKGROUND: Cortical inhibition (CI) deficits have been demonstrated in
      schizophrenia using transcranial magnetic stimulation (TMS). These CI deficits
      may be related to decreased GABA activity which may be involved in schizophrenia
      pathophysiology. Previous cross-sectional studies have also demonstrated greater
      CI in patients treated with clozapine than other typical/atypical antipsychotics.
      However, it is not clear if these differences in CI are a result of treatment
      resistant illness which necessitates clozapine or are related to clozapine
      treatment. METHODS: TMS measures of CI (i.e., cortical silent period (CSP) and
      short-interval cortical inhibition (SICI)) were measured over the motor cortex in
      16 patients with schizophrenia before starting clozapine, then 6 weeks and 6
      months after starting clozapine. RESULTS: CSP was significantly longer after 6
      weeks of treatment with clozapine (p=0.014). From 6 weeks to 6 months, there was
      no significant difference in CSP (p>0.05). Short-interval cortical inhibition
      (SICI) was not significantly different at any time after treatment with clozapine
      (p>0.05). CONCLUSIONS: This prospective-longitudinal study demonstrates that
      treatment with clozapine is associated with an increase in GABAB mediated
      inhibitory neurotransmission. Potentiation of GABAB may be a novel
      neurotransmitter mechanism that is involved in the pathophysiology and treatment
      of schizophrenia.

PMID- 25957488
TI  - Tissue specific response to DNA damage: C. elegans as role model.
AB  - The various symptoms associated with hereditary defects in the DNA damage
      response (DDR), which range from developmental and neurological abnormalities and
      immunodeficiency to tissue-specific cancers and accelerated aging, suggest that
      DNA damage affects tissues differently. Mechanistic DDR studies are, however,
      mostly performed in vitro, in unicellular model systems or cultured cells,
      precluding a clear and comprehensive view of the DNA damage response of
      multicellular organisms. Studies performed in intact, multicellular animals
      models suggest that DDR can vary according to the type, proliferation and
      differentiation status of a cell. The nematode Caenorhabditis elegans has become
      an important DDR model and appears to be especially well suited to understand in
      vivo tissue-specific responses to DNA damage as well as the impact of DNA damage
      on development, reproduction and health of an entire multicellular organism. C.
      elegans germ cells are highly sensitive to DNA damage induction and respond via
      classical, evolutionary conserved DDR pathways aimed at efficient and error-free
      maintenance of the entire genome. Somatic tissues, however, respond differently
      to DNA damage and prioritize DDR mechanisms that promote growth and function. In
      this mini-review, we describe tissue-specific differences in DDR mechanisms that
      have been uncovered utilizing C. elegans as role model. 

PMID- 25957490
TI  - CtIP: A DNA damage response protein at the intersection of DNA metabolism.
AB  - The mammalian CtIP protein and its orthologs in other eukaryotes promote the
      resection of DNA double-strand breaks and are essential for meiotic
      recombination. Here we review the current literature supporting the role of CtIP
      in DNA end processing and the importance of CtIP endonuclease activity in DNA
      repair. We also examine the regulation of CtIP function by post-translational
      modifications, and its involvement in transcription- and replication-dependent
      functions through association with other protein complexes. The tumor suppressor
      function of CtIP likely is dependent on a combination of these roles in many
      aspects of DNA metabolism. 

PMID- 25957487
TI  - Accessing DNA damage in chromatin: Preparing the chromatin landscape for base
      excision repair.
AB  - DNA damage in chromatin comes in many forms, including single base lesions that
      induce base excision repair (BER). We and others have shown that the structural
      location of DNA lesions within nucleosomes greatly influences their accessibility
      to repair enzymes. Indeed, a difference in the location of uracil as small as one
      half turn of the DNA backbone on the histone surface can result in a 10-fold
      difference in the time course of its removal in vitro. In addition, the cell has
      evolved several interdependent processes capable of enhancing the accessibility
      of excision repair enzymes to DNA lesions in nucleosomes, including post
      translational modification of histones, ATP-dependent chromatin remodeling and
      interchange of histone variants in nucleosomes. In this review, we focus on
      different factors that affect accessibility of BER enzymes to nucleosomal DNA. 

PMID- 25957491
TI  - Selective formation of mannosyl-L-arabitol lipid by Pseudozyma tsukubaensis
      JCM16987.
AB  - To develop a structural homolog of mannosylerythritol lipids (MELs), Pseudozyma
      tsukubaensis JCM16987 (known to be a specific producer of the diastereomer type
      of mono-acetylated MEL (MEL-B)) was cultivated in medium containing 4 % (w/v)
      olive oil as the primary carbon source and 4 % L-arabitol as the supplemental
      sugar alcohol. Based on thin-layer chromatography (TLC), the glycolipid extract
      showed two major spots corresponding to MEL-B and an unknown glycolipid (GL1).
      Based on high-performance liquid chromatography after acid hydrolysis, GL1 from
      the L-arabitol culture showed two primary peaks identical to mannose and arabitol
      using the sugar analysis column, and one peak identical to L-arabitol was
      detected using the chiral resolution column. Based on NMR analysis, GL1 was
      identified as mono-acetylated mannosyl-L-arabitol lipid (MLAL-B) consisting of
      mannose, with L-arabitol as the sugar moiety. The observed critical micelle
      concentration (CMC) and surface tension at the CMC (gammaCMC) of MLAL-B were 1.2
      * 10(-5) M and 32.8 mN/m, which were significantly higher than MEL-B (CMC = 3.1 *
      10(-6) M and gammacmc = 26.1 mN/m). Furthermore, based on a water-penetration
      scan, MLAL-B efficiently formed lamellar phase (Lalpha) and myelins at a broad
      concentration range. Thus, the present glycolipid showed higher hydrophilicity
      and/or water solubility and increased our understanding of environmentally
      advanced biosurfactants.

PMID- 25957492
TI  - The gene expression profile of resistant and susceptible Bombyx mori strains
      reveals cypovirus-associated variations in host gene transcript levels.
AB  - High-throughput paired-end RNA sequencing (RNA-Seq) was performed to investigate
      the gene expression profile of a susceptible Bombyx mori strain, Lan5, and a
      resistant B. mori strain, Ou17, which were both orally infected with B. mori
      cypovirus (BmCPV) in the midgut. There were 330 and 218 up-regulated genes, while
      there were 147 and 260 down-regulated genes in the Lan5 and Ou17 strains,
      respectively. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and
      Genomes (KEGG) enrichment for differentially expressed genes (DEGs) were carried
      out. Moreover, gene interaction network (STRING) analyses were performed to
      analyze the relationships among the shared DEGs. Some of these genes were related
      and formed a large network, in which the genes for B. mori cuticular protein RR-2
      motif 123 (BmCPR123) and the gene for B. mori DNA replication licensing factor
      Mcm2-like (BmMCM2) were key genes among the common up-regulated DEGs, whereas the
      gene for B. mori heat shock protein 20.1 (Bmhsp20.1) was the central gene among
      the shared down-regulated DEGs between Lan5 vs Lan5-CPV and Ou17 vs Ou17-CPV.
      These findings established a comprehensive database of genes that are
      differentially expressed in response to BmCPV infection between silkworm strains
      that differed in resistance to BmCPV and implied that these DEGs might be
      involved in B. mori immune responses against BmCPV infection.

PMID- 25957493
TI  - Identification of two novel regulatory genes involved in pristinamycin
      biosynthesis and elucidation of the mechanism for AtrA-p-mediated regulation in
      Streptomyces pristinaespiralis.
AB  - In this study, using a transposon-based strategy, two novel regulatory genes were
      identified as being involved in the biosynthesis of both pristinamycin I (PI) and
      II (PII) in Streptomyces pristinaespiralis, including a TetR-family regulatory
      gene atrA-p (SSDG_00466) and an orphan histidine kinase gene SSDG_02492. The
      mechanism by which AtrA-p exerted a positive role in pristinamycin production was
      elucidated. We showed that deletion of atrA-p resulted in a delayed production of
      both PI and PII as well as reduced PII production. Transcriptional analysis
      integrated with electrophoretic mobility shift assays (EMSAs) demonstrated that
      AtrA-p played a positive role in pristinamycin production by directly activating
      the transcription of two cluster-situated regulatory genes, spbR and papR5, which
      encode a gamma-butyrolactone receptor protein and a TetR-family repressor,
      respectively. The precise AtrA-p-binding sites upstream of these two targets were
      determined, which allowed the identification of a relatively conserved binding
      motif comprising two 5-nt inverted repeats separated by a variable 5-nt sequence
      (5'-GGAAT-n5-ATTCC-3') possibly required for the regulation of AtrA-like
      regulators in Streptomyces. Base substitutions of the AtrA-p-binding sites on the
      genome caused similar decreases in spbR and papR5 transcription as those observed
      in ?atrA-p. Taken together, herein, a novel mechanism for AtrA-dependent
      regulation of antibiotic biosynthesis was revealed in S. pristinaespiralis, which
      is distinct from those of its homologs, AtrA-c from Streptomyces coelicolor, AtrA
      g from Streptomyces griseus, and AtrA from Streptomyces roseosporus that perform
      their effects in antibiotic biosynthesis directly via pathway-specific activator
      genes or the biosynthetic structural genes.

PMID- 25957489
TI  - Preventing replication fork collapse to maintain genome integrity.
AB  - Billions of base pairs of DNA must be replicated trillions of times in a human
      lifetime. Complete and accurate replication once and only once per cell division
      cycle is essential to maintain genome integrity and prevent disease. Impediments
      to replication fork progression including difficult to replicate DNA sequences,
      conflicts with transcription, and DNA damage further add to the genome
      maintenance challenge. These obstacles frequently cause fork stalling, but only
      rarely cause a failure to complete replication. Robust mechanisms ensure that
      stalled forks remain stable and capable of either resuming DNA synthesis or being
      rescued by converging forks. However, when failures do happen the fork collapses
      leading to genome rearrangements, cell death and disease. Despite intense
      interest, the mechanisms to repair damaged replication forks, stabilize them, and
      ensure successful replication remain only partly understood. Different models of
      fork collapse have been proposed with varying descriptions of what happens to the
      DNA and replisome. Here, I will define fork collapse and describe what is known
      about how the replication checkpoint prevents it to maintain genome stability. 

PMID- 25957494
TI  - Biosynthesis of hydrocarbons and volatile organic compounds by fungi:
      bioengineering potential.
AB  - Recent advances in the biological production of fuels have relied on the
      optimization of pathways involving genes from diverse organisms. Several recent
      articles have highlighted the potential to expand the pool of useful genes by
      looking to filamentous fungi. This review highlights the enzymes and organisms
      used for the production of a variety of fuel types and commodity chemicals with a
      focus on the usefulness and promise of those from filamentous fungi. 

PMID- 25957486
TI  - Chromatin plasticity in response to DNA damage: The shape of things to come.
AB  - DNA damage poses a major threat to cell function and viability by compromising
      both genome and epigenome integrity. The DNA damage response indeed operates in
      the context of chromatin and relies on dynamic changes in chromatin organization.
      Here, we review the molecular bases of chromatin alterations in response to DNA
      damage, focusing on core histone mobilization in mammalian cells. Building on our
      current view of nucleosome dynamics in response to DNA damage, we highlight open
      challenges and avenues for future development. In particular, we discuss the
      different levels of regulation of chromatin plasticity during the DNA damage
      response and their potential impact on cell function and epigenome maintenance. 

PMID- 25957495
TI  - Global alterations of the transcriptional landscape during yeast growth and
      development in the absence of Ume6-dependent chromatin modification.
AB  - Chromatin modification enzymes are important regulators of gene expression and
      some are evolutionarily conserved from yeast to human. Saccharomyces cerevisiae
      is a major model organism for genome-wide studies that aim at the identification
      of target genes under the control of conserved epigenetic regulators. Ume6
      interacts with the upstream repressor site 1 (URS1) and represses transcription
      by recruiting both the conserved histone deacetylase Rpd3 (through the co
      repressor Sin3) and the chromatin-remodeling factor Isw2. Cells lacking Ume6 are
      defective in growth, stress response, and meiotic development. RNA profiling
      studies and in vivo protein-DNA binding assays identified mRNAs or transcript
      isoforms that are directly repressed by Ume6 in mitosis. However, a comprehensive
      understanding of the transcriptional alterations, which underlie the complex
      ume6Delta mutant phenotype during fermentation, respiration, or sporulation, is
      lacking. We report the protein-coding transcriptome of a diploid MAT a/alpha wild
      type and ume6/ume6 mutant strains cultured in rich media with glucose or acetate
      as a carbon source, or sporulation-inducing medium. We distinguished direct from
      indirect effects on mRNA levels by combining GeneChip data with URS1 motif
      predictions and published high-throughput in vivo Ume6-DNA binding data. To gain
      insight into the molecular interactions between successive waves of Ume6
      dependent meiotic genes, we integrated expression data with information on
      protein networks. Our work identifies novel Ume6 repressed genes during growth
      and development and reveals a strong effect of the carbon source on the
      derepression pattern of transcripts in growing and developmentally arrested
      ume6/ume6 mutant cells. Since yeast is a useful model organism for chromatin
      mediated effects on gene expression, our results provide a rich source for
      further genetic and molecular biological work on the regulation of cell growth
      and cell differentiation in eukaryotes. 

PMID- 25957496
TI  - Weaning critically ill patients from mechanical ventilation: A prospective cohort
      study.
AB  - PURPOSE: A proposal was made at the International Consensus Conference to
      classify weaning of patients in intensive care units from mechanical ventilation
      into simple, difficult, and prolonged weaning groups based on the difficulty and
      length of the weaning process. The objective of the present study was to
      determine the incidence and outcome of weaning according to these new categories.
      METHODS: We examined the weaning of patients in intensive care units from
      mechanical ventilation in a prospective multicenter cohort study. RESULTS: In
      total, 343 patients were included in the final analysis. Simple, difficult, and
      prolonged weaning occurred in 200 (58%), 99 (29%), and 44 (13%) patients,
      respectively. Hospital mortality rates were higher for patients in the prolonged
      weaning group than in the simple and difficult weaning groups. Multivariate
      analysis revealed that a lower Glasgow Coma Scale score (P < .014) and
      hypercapnia at the beginning of the first spontaneous breathing trial (P = .038)
      were independent predictors of prolonged weaning. CONCLUSIONS: Patients who
      experienced prolonged weaning had significantly higher mortality rates than
      patients who experienced either simple or difficult weaning. A lower Glasgow Coma
      Scale score and hypercapnia at the beginning of the weaning process were
      independent risk factors for prolonged weaning.

PMID- 25957499
TI  - Safety profile and feasibility of early physical therapy and mobility for
      critically ill patients in the medical intensive care unit: Beginning experiences
      in Korea.
AB  - PURPOSE: To evaluate risk factors for potential safety events during mobility
      physical therapy sessions in the medical intensive care unit. METHODS: The safety
      profiles and potential risk factors of 99 patients who were admitted to the
      medical intensive care unit of a single teaching hospital in Korea between May 1
      and December 31, 2013, were retrospectively evaluated. RESULTS: A total of 26
      potential safety events (5.0%; 95% confidence interval [CI], 3.4%-7.3%) during
      520 mobilization sessions were observed in 17 (17.2%; 95% CI, 10.6%-26.4%) of 99
      patients. The common potential safety events were as follows in order of
      frequency: 11 events of tachypnea or bradypnea (2.1%; 95% CI, 1.1%-3.9%), 6
      events of desaturation (1.2 %; 95% CI, 0.5%-2.6%), 4 events of tachypnea or
      bradycardia (0.8%; 95% CI, 0.3%-2.1%), 4 events of patients' intolerance (0.8%;
      95% CI, 0.3%-2.1%), and 1 event of tracheostomy tube removal (0.2%; 95% CI, 0%
      1.2%). In multivariate analysis, the use of extracorporeal membrane oxygenation
      was associated with potential adverse events with an adjusted odds ratio of 5.8
      (95% CI, 2.2-15.6), respectively. CONCLUSION: Early mobility physical therapy
      performed by a newly established group was feasible for critically ill patients
      in Korea. However, potential safety events need to be monitored carefully for
      patients with extracorporeal membrane oxygenation support.

PMID- 25957497
TI  - alpha-1-Acid glycoprotein as a biomarker for the early diagnosis and monitoring
      the prognosis of sepsis.
AB  - OBJECTIVE: To explore the value of alpha-1-acid glycoprotein (AGP) for the early
      diagnostic and prognostic assessment of patients with sepsis. METHODS: Eighty
      five patients with systemic inflammatory response syndrome (SIRS) and 192
      patients with sepsis were enrolled. White blood cell counts and serum levels of
      AGP, C-reactive protein, and procalcitonin were tested on the day of admission to
      intensive care unit (ICU; day 1) and the following days 3, 5, 7, and 10. RESULTS:
      The sepsis group exhibited significantly higher levels of AGP than did the SIRS
      group on day 1 (P < .05); the area under the curve (AUC) of AGP was 0.869 with a
      specificity of 0.902 on diagnosis of sepsis. The differences were statistically
      significant among sepsis subgroups. On prognostic assessment, the areas under the
      curve of AGP, Sequential Organ Failure Assessment (SOFA) scores, and SOFA + AGP
      on ICU admission were 0.793, 0.813, and 0.878, respectively. The results of
      logistic regression showed that the odds ratios of AGP, SOFA, Acute Physiology
      and Chronic Health Evaluation II, and the length of ICU stay were 1.450, 1.212,
      1.673, and 1.130. CONCLUSIONS: alpha-1-Acid glycoprotein could distinguish sepsis
      from SIRS and also be used to effectively assess the severity of sepsis. In
      addition, combined AGP and SOFA scores had a great predicting value in prognosis
      of sepsis.

PMID- 25957500
TI  - Extracoronary Thoracic and Coronary Artery Calcifications on Chest CT for Lung
      Cancer Screening: Association with Established Cardiovascular Risk Factors - The
      "CT-Risk" Trial.
AB  - RATIONALE AND OBJECTIVES: To investigate the correlation between prevalence and
      degree of coronary artery calcification (CAC) and extracoronary calcifications
      (ECCs), scored quantitatively according to Agatston and semiquantitatively by
      visual analysis, in chest computed tomography (CT) studies obtained for lung
      cancer screening in asymptomatic subjects and in patients with known coronary
      heart disease (CHD), and to compare the association of ECC and CAC to established
      cardiovascular risk factors. MATERIALS AND METHODS: Prospective study on 501
      males (67 +/- 8 years) with a history of working dust exposure who underwent
      nongated low-dose chest CT for lung cancer screening. Of these, 63 (12.6%) had a
      history of CHD, the remaining 438 subjects (87.4%) were clinically asymptomatic
      and without a history of CHD. On the day of the CT study, subjects underwent a
      thorough clinical examination including blood tests and completed a standardized
      questionnaire to establish a complete medical history. ECC and CAC scores were
      quantified according to Agatston and, in addition, by visual rating of calcium
      load of individual vessel territories on a five-point scale from "absent" to
      "extensive." Results were correlated with the respective subjects' cardiovascular
      risk factors and with the presence or absence of CHD. RESULTS: ECC scores
      correlated significantly with CAC scores (two-sided Spearman 0.515; P < .001).
      ECC scores were associated significantly (P < .001) with cardiovascular risk
      factors (smoking history, hypertension, diabetes, and hypercholesterolemia) and
      with subjects' Framingham/prospective cardiovascular munster study scores,
      whereas CAC scores were associated only with the presence of
      hypercholesterolemia. CAC scores were strongly associated with CHD than ECC
      scores (area under the curve, 0.88 vs. 0.66 at receiver operating characteristic
      analysis). Visual scoring of ECC/CAC load correlated closely with the respective
      Agatston values (P < .001) and revealed the same association (or lack thereof)
      with cardiovascular risk factors/CHD. CONCLUSIONS: In nongated low-dose CT for
      lung cancer screening, CAC and ECC load can be accurately established by visual
      analysis. ECC and CAC scores correlate closely, but not perfectly. There is a
      strong association between established cardiovascular risk factors and ECC load,
      but not CAC load, providing further evidence that ECC scoring may complement CAC
      scoring for broader risk assessment, for example, regarding prediction of
      extracoronary vascular events.

PMID- 25957498
TI  - Pharmacologic prevention and treatment of delirium in intensive care patients: A
      systematic review.
AB  - PURPOSE: The purpose of the study is to determine if pharmacologic approaches are
      effective in prevention and treatment of delirium in critically ill patients.
      MATERIALS AND METHODS: We performed a systematic search to identify publications
      (from January 1980 to September 2014) that evaluated the pharmacologic
      interventions to treat or prevent delirium in intensive care unit (ICU) patients.
      RESULTS: From 2646 citations, 15 studies on prevention (6729 patients) and 7
      studies on treatment (1784 patients) were selected and analyzed. Among studies
      that evaluated surgical patients, the pharmacologic interventions were associated
      with a reduction in delirium prevalence, ICU length of stay, and duration of
      mechanical ventilation, but with high heterogeneity (respectively, I(2) = 81%, P
      = .0013; I(2) = 97%, P < .001; and I(2) = 97%). Considering treatment studies,
      only 1 demonstrated a significant decrease in ICU length of stay using
      dexmedetomidine compared to haloperidol (Relative Risk, 0.62 [1.29-0.06]; I(2) =
      97%), and only 1 found a shorter time to resolution of delirium using quetiapine
      (1.0 [confidence interval, 0.5-3.0] vs 4.5 [confidence interval, 2.0-7.0] days; P
      = .001). CONCLUSION: The use of antipsychotics for surgical ICU patients and
      dexmedetomidine for mechanically ventilated patients as a preventive strategy may
      reduce the prevalence of delirium in the ICU. None of the studied agents that
      were used for delirium treatment improved major clinical outcome, including
      mortality.

PMID- 25957501
TI  - Trends in CT Utilization for Pediatric Fall Patients in US Emergency Departments.
AB  - RATIONALE AND OBJECTIVES: Falls are a common cause of emergency department (ED)
      visits in the United States. We evaluated trends in computed tomography (CT)
      utilization for pediatric fall victims in the United States from 2001 to 2010.
      MATERIALS AND METHODS: Using the National Hospital Ambulatory Medical Care Survey
      from 2001 to 2010, we identified all visits of pediatric (aged <18 years)
      patients presenting to EDs after falls. This database surveys approximately 500
      EDs per year for 4 weeks providing national estimates on ED resource utilization
      and outcomes. We studied trends in CT utilization and proportion of visits with
      life-threatening conditions after falls. We also studied the association between
      CT utilization rates and demographic characteristics and admission status.
      RESULTS: A total of 9763 unweighted observations for a total of 32,432,686
      pediatric fall patients were seen in US EDs from 2001 to 2010. The proportion of
      pediatric fall patients receiving CT increased from 5.3% in 2001 to a peak of
      16.6% in 2009 and decreased to 11.3% in 2010, whereas the proportion of pediatric
      fall patients with life-threatening conditions fluctuated between 1.2% and 3.3%
      during this period. In multivariate logistic regression analysis, each increasing
      year was independently associated with CT utilization (odds ratio [OR], 1.15; 95%
      confidence interval [CI], 1.14-1.16). Patients aged 0-1 years had higher odds of
      CT utilization than patients aged 13-17 years (OR, 2.27; 95% CI, 2.26-2.27).
      CONCLUSIONS: There was a twofold increase in CT utilization among pediatric fall
      visits from 2001 to 2010. When controlling for demographic and clinical
      variables, increasing year was independently associated with CT utilization.
      These findings suggest that CT may be overutilized among pediatric fall patients.

PMID- 25957502
TI  - The Value of Nonenhanced Single-Source Dual-Energy CT for Differentiating
      Metastases From Adenoma in Adrenal Glands.
AB  - RATIONALE AND OBJECTIVES: To evaluate the value of the nonenhanced single-source
      dual-energy computed tomography (ssDECT) in differentiating metastases from
      adenomas in adrenal glands. MATERIALS AND METHODS: This retrospective study was
      approved by our Institutional Review Board, and written informed consent was
      waived. One hundred twelve patients (66 men:46 women; mean age, 58 years) with 63
      adrenal metastases (AMs) and 64 adrenal adenomas (AAs) underwent a plain dual
      energy spectral CT imaging from August 2011 to December 2013 were included. The
      fat (water) density (DFa [Wa]) from the material decomposition (MD) images and CT
      number and effective atomic number (eff-Z) from the virtual monochromatic
      spectral (VMS) image sets were measured for the AMs and AAs. The spectral
      Hounsfield unit (HU) curve (CT number as a function of photon energy from 40 to
      140 keV) was generated, and its slope (K) was calculated. The difference of these
      parameters between AMs and AAs was statistically compared by the Wilcoxon rank
      sum test. Receiver operating characteristic curve (ROC) curves were used to
      compare the diagnostic efficacies of these measures in the identification of AAs
      and AMs. The distribution of spectral HU curve was analyzed using the chi-square
      test in terms of its slope K: ascending (K > 0.1), straight (-0.1 <= K <= 0.1),
      and descending (K < -0.1). RESULTS: 1) The CT number (medium, range) of
      metastases (50.47, 29.93 HU at 40 keV and 29.00, 9.36 HU at 140 keV) was
      significantly higher than that of adenomas (-0.76, 33.04 to 13.73, 18.96 HU) at
      each energy level from 40 to 140 keV (P < .05). 2) The fat concentration of
      metastases (-177.37, 296.38 mg/mL) was statistically lower than that of adenomas
      (126.73, 328.07 mg/mL; P < .05). 3) The eff-Z of metastases (7.76, 0.23) was
      significantly higher than that of adenomas (7.42, 0.32; P < .05). 4) With CT
      number of VMS image at 40 keV of 21.78 HU as a threshold, the sensitivity and
      specificity for differentiating metastases from adenomas was 92.1% and 76.6%,
      respectively, and the area under the ROC curve was 0.90. 5) The spectral curve
      types included 3.2% (2 of 63) ascending, 20.6% (13 of 63) straight, and 76.2% (48
      of 63) descending for the metastases, whereas the corresponding numbers were
      60.9% (39 of 64), 21.9% (14 of 64), and 17.2% (11 of 64) for the adenomas. The
      difference was statistically significant (X(2) = 56.63; P < .05). CONCLUSIONS:
      The nonenhanced ssDECT enables a multiparametric approach to provide an excellent
      sensitivity for identifying AMs from AAs.

PMID- 25957504
TI  - Individual differences in involvement of the visual object recognition system
      during visual word recognition.
AB  - Individuals with dyslexia often evince reduced activation during reading in left
      hemisphere (LH) language regions. This can be observed along with increased
      activation in the right hemisphere (RH), especially in areas associated with
      object recognition - a pattern referred to as RH compensation. The mechanisms of
      RH compensation are relatively unclear. We hypothesize that RH compensation
      occurs when the RH object recognition system is called upon to supplement an
      underperforming LH visual word form recognition system. We tested this by
      collecting ERPs while participants with a range of reading abilities viewed
      words, objects, and word/object ambiguous items (e.g., "SMILE" shaped like a
      smile). Less experienced readers differentiate words, objects, and ambiguous
      items less strongly, especially over the RH. We suggest that this lack of
      differentiation may have negative consequences for dyslexic individuals
      demonstrating RH compensation. 

PMID- 25957503
TI  - Baicalein inhibits prostate cancer cell growth and metastasis via the caveolin
      1/AKT/mTOR pathway.
AB  - Prostate cancer (PCa) is lethal type of genitourinary cancer due to its high
      morbidity and gradual resistance to androgen deprivation therapy. Accumulating
      evidence has recently suggested that the daily intake of flavonoids is negatively
      correlated with the risk of cancer. In this study, we aimed to investigate the
      potential effects of baicalein on androgen-independent PCa cells and the
      underlying mechanisms through which baicalein exerts its actions. Cell viability
      and flow cytometric apoptosis assays indicated that baicalein potently suppressed
      the growth and induced the apoptosis of DU145 and PC-3 cells in a time- and dose
      dependent manner. Consistently, the inhibitory effects of baicalein on migration
      and invasion were also observed in vitro. Mechanistically, we found that
      baicalein can suppress caveolin-1 and the phosphorylation of AKT and mTOR in a
      time- and dose-dependent manner. Moreover, the inhibition of the activation of
      AKT with LY294002 significantly promoted the apoptosis and metastasis induced by
      baicalein. In conclusion, these findings suggested that baicalein can induce
      apoptosis and inhibit metastasis of androgen-independent PCa cells through
      inhibition of the caveolin-1/AKT/mTOR pathway, which implies that baicalein may
      be a potential therapeutic agent for the treatment of androgen-independent
      prostate cancer patients. 

PMID- 25957507
TI  - [A case report on embolism prevention in atrial fibrillation/flutter: dual
      antiplatelet therapy, please no!].

PMID- 25957505
TI  - Electrical stimulation mapping of nouns and verbs in Broca's area.
AB  - Electric stimulation mapping (ESM) is frequently used during brain surgery to
      localise higher cognitive functions to avoid post-chirurgical disabilities.
      Experiments with brain imaging techniques and neuropsychological studies showed
      differences in the cortical representation and processing of nouns and verbs. The
      goal of the present study was to investigate whether electric stimulation in
      specific sites in the frontal cortex disrupted noun and verb production
      selectively. We found that most of the stimulated areas showed disruption of both
      verbs and nouns at the inferior frontal gyrus. However, when selective effects
      were obtained, verbs were more prone to disruption than nouns with important
      individual differences. The overall results indicate that selective impairments
      can be observed at inferior and middle frontal regions and the action naming task
      seems to be more suitable to avoid post-chirurgical language disabilities, as it
      shows a greater sensitivity to disruption with ESM than the classical object
      naming task. 

PMID- 25957510
TI  - Autopsy findings for a case of acute gastric volvulus in a child.
AB  - Acute gastric volvulus resulting in abdominal compartment syndrome was determined
      to be the cause of death in a 4-year-old girl who presented with abdominal
      distension. At about 1AM on the day of her death, she was brought to our
      emergency medical center. Physical examination and plain abdominal X-ray revealed
      pronounced gastric dilatation. A decompression procedure was performed, followed
      by observation. She went into cardiopulmonary arrest around 1PM on the same day
      and died. Postmortem investigation, including an autopsy and computed tomography
      (CT), was performed to determine the cause of death. The findings included that
      the stomach was severely distended. Evidence was seen of mucosal hemorrhage in
      the gastric mucosa on the greater curvature side, which was thinned in places but
      without perforation. No necrosis of the gastric mucosa was observed; reversible
      changes were evident on histopathological examination. The postmortem CT images
      suggested that the pyloric region was positioned cranioventrally to the cardiac
      region. None of the findings indicated sudden blockage, and the cause of death
      was determined to be acute gastric volvulus resulting in abdominal compartment
      syndrome. The abnormal placement of the organs was difficult to determine based
      on physical examination alone; postmortem CT and careful examination were helpful
      in conducting the autopsy in this case. 

PMID- 25957509
TI  - Surgical site infection in high-energy peri-articular tibia fractures with intra
      wound vancomycin powder: a retrospective pilot study.
AB  - BACKGROUND: Surgical site infections (SSI) continue to be a significant source of
      morbidity despite the introduction of perioperative intravenous antibiotics. Our
      objective was to assess the efficacy of local vancomycin powder on lowering deep
      SSI rates in high-energy tibial plateau and pilon fractures. MATERIALS AND
      METHODS: A retrospective review of all tibial plateau and pilon fractures treated
      in 2012 at our level I trauma center identified 222 patients. Of these, 107
      patients sustained high-energy injuries that required staged fixation, and 93 had
      minimum 6 month follow-up. Ten patients received 1 gram vancomycin powder
      directly into the surgical wound at the time of definitive fixation, and the
      remaining 83 patients served as controls. SSI was defined according to criteria
      from the Centers for Disease Control. Demographic data, patient comorbidities,
      injury and treatment details, and infection details were recorded. Descriptive
      and comparative statistics were performed. RESULTS: Amongst the vancomycin powder
      group, 1 patient (10 %) developed a deep SSI; in the control group, 14 (16.7 %)
      developed deep SSI. The rate of deep SSI between the groups was not statistically
      significantly different (P = 1.0). The groups were statistically similar with
      regard to injuries, treatment, comorbidities, and infectious outcomes (P values
      range = 0.06-1.0). CONCLUSIONS: The application of local vancomycin powder into
      surgical wounds of high-energy tibial plateau and pilon fractures did not reduce
      the rate of deep SSI in this retrospective review. There is a need to find
      effective, cheap, and widely available methods for prevention of SSI. Basic
      science and larger prospective clinical studies are needed to further delineate
      the role of local vancomycin powder as a modality to reduce deep SSI in extremity
      trauma.

PMID- 25957506
TI  - Exploiting the yeast stress-activated signaling network to inform on stress
      biology and disease signaling.
AB  - Healthy cells utilize intricate systems to monitor their environment and mount
      robust responses in the event of cellular stress. Whether stress arises from
      external insults or defects due to mutation and disease, cells must be able to
      respond precisely to mount the appropriate defenses. Multi-faceted stress
      responses are generally coupled with arrest of growth and cell-cycle progression,
      which both limits the transmission of damaged materials and serves to reallocate
      limited cellular resources toward defense. Therefore, stress defense versus rapid
      growth represent competing interests in the cell. How eukaryotic cells set the
      balance between defense versus proliferation, and in particular knowledge of the
      regulatory networks that control this decision, are poorly understood. In this
      perspective, we expand upon our recent work inferring the stress-activated
      signaling network in budding yeast, which captures pathways controlling stress
      defense and regulators of growth and cell-cycle progression. We highlight
      similarities between the yeast and mammalian stress responses and explore how
      stress-activated signaling networks in yeast can inform on signaling defects in
      human cancers. 

PMID- 25957508
TI  - Nitric oxide-associated chondrocyte apoptosis in trauma patients after high
      energy lower extremity intra-articular fractures.
AB  - BACKGROUND: The primary goal of this study was to identify nitric oxide (NO)
      induced apoptosis in traumatized chondrocytes in intra-articular lower extremity
      fractures and the secondary goal was to identify the timeline of NO-induced
      apoptosis after injury. MATERIALS AND METHODS: This is a prospective collection
      of samples of human cartilage harvested at the time of surgery to measure
      apoptotic cell death and the presence of NO by immunohistochemistry. Three
      patients met the criteria for control subjects and eight patients sustained high
      energy intra-articular fractures and were included in the study. Subjects who
      sustained intra-articular acetabular, tibial, calcaneal and talus fracture had
      articular cartilage harvested at the time of surgical intervention. All 8
      patients underwent open reduction and internal fixation of the displaced intra
      articular fractures. The main outcome measures were rate of apoptosis, degree of
      NO-induced apoptosis in chondrocytes, and the timeline of NO-induced apoptosis
      after high-energy trauma. RESULTS: The percentage of apoptotic chondrocytes was
      higher in impacted samples than in normal cartilage (56 vs 4 %), confirming the
      presence of apoptosis after intra-articular fracture. The percentage of cells
      with NO was greater in apoptotic cells than in normal cells (59 vs 20 %),
      implicating NO-induction of apoptosis. The correlation between chondrocyte
      apoptosis and increasing time from injury was found to be -0.615, indicating a
      decreasing rate of apoptosis post injury. CONCLUSIONS: The data showed the
      involvement of NO-induced apoptosis of chondrocytes after high-energy trauma,
      which decreased with time from injury.

PMID- 25957512
TI  - Liquid based microbiological transport systems: conformity assessment of two
      commercial devices.
AB  - We compared two types of liquid-based microbiology devices for microorganism
      viability according to standardized quantitative elution method CLSI M40-A2. The
      eSwab(r) met CLSI acceptance criteria of viability maintenance for all
      microorganisms tested. The Sigma-Transwab(r) failed to meet CLSI acceptance
      criteria for Peptostreptococcus anaerobius, Prevotella melaninogenica,
      Fusobacterium nucleatum and Haemophilus influenzae. 

PMID- 25957513
TI  - The Integral Method, a new approach to quantify bactericidal activity.
AB  - The bactericidal activity (BA) of antimicrobial agents is generally derived from
      the results of killing assays. A reliable quantitative characterization and
      particularly a comparison of these substances, however, are impossible with this
      information. We here propose a new method that takes into account the course of
      the complete killing curve for assaying BA and that allows a clear-cut
      quantitative comparison of antimicrobial agents with only one number. The new
      Integral Method, based on the reciprocal area below the killing curve, reliably
      calculates an average BA [log10 CFU/min] and, by implementation of the agent's
      concentration C, the average specific bactericidal activity SBA=BA/C [log10
      CFU/min/mM]. Based on experimental killing data, the pertaining BA and SBA values
      of exemplary active halogen compounds were established, allowing quantitative
      assertions. N-chlorotaurine (NCT), chloramine T (CAT), monochloramine (NH2Cl),
      and iodine (I2) showed extremely diverging SBA values of 0.0020+/-0.0005, 1.11+/
      0.15, 3.49+/-0.22, and 291+/-137log10 CFU/min/mM, respectively, against
      Staphylococcus aureus. This immediately demonstrates an approximately 550-fold
      stronger activity of CAT, 1730-fold of NH2Cl, and 150,000-fold of I2 compared to
      NCT. The inferred quantitative assertions and conclusions prove the new method
      suitable for characterizing bactericidal activity. Its application comprises the
      effect of defined agents on various bacteria, the consequence of temperature
      shifts, the influence of varying drug structure, dose-effect relationships,
      ranking of isosteric agents, comparison of competing commercial antimicrobial
      formulations, and the effect of additives.

PMID- 25957511
TI  - TM7 detection in human microbiome: Are PCR primers and FISH probes specific
      enough?
AB  - TM7 appears important and omnipresent because it is repeatedly detected by
      molecular techniques in diverse environments. Here we report that most of primers
      and FISH probes thought to be TM7-specific do hybridize with multiple species
      from oral and vaginal cavity. This calls for re-examination of TM7 distribution
      and abundance. 

PMID- 25957515
TI  - Claudin switching: Physiological plasticity of the Tight Junction.
AB  - Tight Junctions (TJs) are multi-molecular complexes in epithelial tissues that
      regulate paracellular permeability. Within the TJ complex, claudins proteins span
      the paracellular space to form a seal between adjacent cells. This seal allows
      regulated passage of ions, fluids, and solutes, contingent upon the complement of
      claudins expressed. With as many as 27 claudins in the human genome, the TJ seal
      is complex indeed. This review focuses on changes in claudin expression within
      the epithelial cells of the gastrointestinal tract, where claudin differentiation
      results in several physiologically distinct TJs within the lifetime of the cell.
      We also review mechanistic studies revealing that TJs are highly dynamic, with
      the potential to undergo molecular remodeling while structurally intact.
      Therefore, physiologic Tight Junction plasticity involves both the adaptability
      of claudin expression and gene specific retention in the TJ; a process we term
      claudin switching. 

PMID- 25957514
TI  - Proposal of a new cutoff for Nugent criteria in the diagnosis of bacterial
      vaginosis.
AB  - OBJECTIVES: Treatment for lower genital tract infections is the major demand for
      gynecological services in public and private health centers in Brazil. The aims
      of this study were to evaluate the diagnostic resources proposed by Amsel,
      comparing them with the microflora evaluation by the Nugent score and thus
      propose a new cutoff point in this rating score, showing the complementarity of
      both diagnostic criteria. METHODS: A total of 136 female patients aged between 18
      and 69years were evaluated and had their vaginal discharge samples collected.
      RESULTS: Diagnosis based on the isolated analysis of the Amsel's criteria may
      lead clinicians to apply inadequate treatment techniques. When patients were
      evaluated according to the Amsel criteria, it was seen that the presence of clue
      cells had a higher Kappa index in the vaginosis diagnosis; when patients were
      distributed according to the Nugent criteria in relation to each Amsel criterion,
      it was observed that clue cells differentiate positive patients more efficiently
      than the Nugent criteria. In the proposed cutoff point, the identification of
      clue cells complied with pH alterations. It also complied with the positive
      Nugent score (>=7). However, when clue cells were analyzed by both Amsel and
      Nugent methods, the diagnostic conclusion was reached once this was the parameter
      with a higher Kappa value. CONCLUSION: The Amsel method could be used as a
      screening tool whereas the Nugent score could serve as a confirmatory resource of
      diagnosis, considering a new assessment cutoff point (negative 0-6 and positive
      >=7).

PMID- 25957516
TI  - Assembly and function of claudins: Structure-function relationships based on
      homology models and crystal structures.
AB  - The tetra-span transmembrane proteins of the claudin family are critical
      components of formation and function of tight junctions (TJ). Homo- and
      heterophilic side-by-side (cis) and intercellular head-to-head (trans)
      interactions of 27 claudin-subtypes regulate tissue-specifically the paracellular
      permeability and/or tightness between epithelial or endothelial cells. This
      review highlights the functional impact that has been identified for particular
      claudin residues by relating them to structural features and architectural
      characteristics in the light of structural advances, which have been contributed
      by homology models, cryo-electron microscopy and crystal structures. The
      differing contributions to the TJ functionalities by claudins are dissected for
      the transmembrane region, the first and the second extracellular loop of claudins
      separately. Their particular impact to oligomerisation and TJ strand- and pore
      formation is surveyed. Detailed knowledge about structure-function relationships
      about claudins helps to reveal the molecular mechanisms of TJ assembly and
      regulation of paracellular permeability, which is yet not fully understood. 

PMID- 25957517
TI  - Dendritic cells and monocyte-derived cells: Two complementary and integrated
      functional systems.
AB  - Dendritic cells (DC) are professional antigen sensing and presenting cells that
      link innate and adaptive immunity. Within the DC population multiple
      subpopulations exist, each possessing distinct phenotypic and functional
      properties, together forming a complex cellular network capable of integrating
      multiple environmental signals and determining immunity or tolerance.
      Inflammatory monocyte-derived DC are considered a subtype of DC generated upon
      inflammation. However, we now know that rather than being a bona fide DC subtype,
      these monocyte-derived cells (MC) more likely represent a distinct type of highly
      plastic cell that is able to acquire a multitude of functional capabilities, some
      of which are shared with DC. In this review, we will first discuss the latest
      developments in our understanding of the organization of the DC and MC networks
      in both mouse and human and of the functional specializations of their
      subpopulations. Finally, we will discuss how DC and MC form two complementary and
      integrated functional systems. 

PMID- 25957518
TI  - [Ocular lesions of artificial depigmentation].
AB  - PURPOSE: To evaluate the type and frequency of the ocular lesions found in
      patients practicing artificial depigmentation. PATIENTS AND METHOD: We conducted
      a prospective study over 3 months involving 108 patients, of whom 72 underwent
      depigmentation, and 36 did not, representing the controls. RESULTS: Among
      patients undergoing depigmentation, 100% were female, of whom 34.72% developed
      ocular lesions. Exogenous ochronosis lesions of the eyelid predominated (34.72%),
      followed by ocular ochronosis (25.81%). Cataract (19.35%) and glaucoma (6.45%)
      were the least frequent. Among the untreated, only 19.44% had ocular lesions.
      These included cataract (57.14%) and glaucoma (42.86%). Ocular lesions were more
      frequent in patients using products containing hydroquinone. CONCLUSION:
      Artificial depigmentation is responsible for ocular lesions of variable severity.
      Our study highlights the importance of the raising awareness amongst the general
      population of the complications of artificial depigmentation, particularly the
      ocular lesions.

PMID- 25957519
TI  - [Dengue fever-related edematous maculopathy and foveolitis: Natural history
      documented by Optical Coherence Tomography].

PMID- 25957521
TI  - Healing of venous ulcers using compression therapy: Predictions of a mathematical
      model.
AB  - Venous Leg Ulceration (VLU) is a chronic condition for which healthcare systems
      worldwide face rising treatment costs. VLU can be due to sustained venous
      hypertension which causes the veins to become cuffed with fibrin, inhibiting the
      supply of nutrients to the wound site. For patients that cannot tolerate
      compression therapy with an inelastic short stretch (SS) bandage, the mainstay
      treatment, an elastic three layered (3L) bandage is an alternative. In this
      paper, a mathematical model is developed to investigate whether the healing of
      venous ulcers under SS and 3L bandages occurs at different rates and to postulate
      the reason for any difference. The two treatments were applied to a simplified
      wound geometry, under the assumption that the rate limiting step of healing is
      the supply of oxygen to the wounded tissue. Clinical data of wound size over time
      under the two treatments from Weller et al. (2012) was used to fit key, unknown,
      model parameters using a least squares approach. Numerical results are presented
      for the oxygen distribution within the wound space, using the fitted parameter
      values. The 3L bandage allows more oxygen flow into the wound than the SS bandage
      and, hence, the 3L bandage results in faster healing, however the difference is
      more significant for wounds of larger initial size. The model can be used as a
      predictive tool in a clinical setting to estimate the time to heal for a wound of
      a given initial size, treated with either a SS or 3L bandage. 

PMID- 25957522
TI  - Founder of systems chemistry and foundational theoretical biologist: Tibor Ganti
      (1933-2009).
AB  - With his chemoton theory theoretical biologist and chemical engineer Tibor Ganti
      was one of the most outstanding intellects behind systems chemistry and the at
      the foundations of theoretical biology. A brief review of his oeuvre is
      presented. This essay introduces a special issue dedicated to his memory. 

PMID- 25957520
TI  - [Early postoperative intraocular pressure after phacoemulsification: Normal
      patients versus glaucoma patients].
AB  - OBJECTIVE: To compare intraocular pressure (IOP) during the first month following
      cataract surgery among patients with primary open-angle glaucoma (POAG) and non
      glaucomatous patients. MATERIALS AND METHODS: This longitudinal observational
      study included 19 glaucoma patients and 18 healthy patients scheduled for
      phacoemulsification with IOL implantation between December 2013 and April 2014.
      IOP was measured preoperatively, on the day of surgery (j0), the next day (j1),
      one week (j7) and one month after (M1). The usual antiglaucoma medications were
      continued without any modification compared to the preoperative medications. Oral
      treatment with a carbonic anhydrase inhibitor was initiated in the case of ocular
      hypertension above 30mmHg. RESULTS: IOP in glaucoma patients was 18.42 and
      21.16mmHg respectively at j0 and j1 versus 12.94 and 13.78mmHg in non
      glaucomatous patients. The difference was significant with P=0.05. There was also
      more ocular hypertension over 30mmHg in the POAG group (31.5% vs. none in the non
      glaucomatous group, P<0.05). CONCLUSION: Glaucoma patients, even stabilized on
      topical medications, are more likely to experience IOP spikes immediately after
      uncomplicated cataract surgery. High risk patients should have closer monitoring
      with IOP measurement the day of or the day after surgery. Further studies are
      needed to evaluate the effectiveness of prophylactic anti-hypertensive treatment.

PMID- 25957523
TI  - Chloroquine-induced scratching is mediated by NO/cGMP pathway in mice.
AB  - Chloroquine (CQ), a 4-aminoquinoline drug, has long been used in the treatment
      and prevention of malaria. However its side effect generalized pruritus
      contributes to treatment failures, and consequently results in the development of
      chloroquine resistant strains of Plasmodium falciparum. It was proposed that the
      administration of CQ correlated with increase in nitric oxide (NO) production.
      Nitric oxide is involved in some pruritic disorders such as atopic dermatitis,
      psoriasis and scratching behavior evoked by pruritogens like substance P.
      Therefore, the aim of this study was to investigate the involvement of NO/cGMP
      pathway in CQ-induced scratching in mice. Scratching behaviors were recorded by a
      camera after intradermal (ID) injection of CQ in the shaved rostral back of the
      mice. The results obtained show that CQ elicited scratching in a dose-dependent
      manner with a peak effective dose of 400MUg/site. Injection of non-specific NOS
      inhibitor, N-nitro-l-arginine methyl ester or neuronal NOS selective inhibitor
      and 7-nitroindazole, reduced CQ-induced scratching significantly. On the other
      hand, administration of aminoguanidine as inducible NOS inhibitor has no
      inhibitory effect on this behavior. Also, injection of l-arginine as a precursor
      of NO significantly increased this response. Conversely, accumulation of cGMP by
      sildenafil as a selective phosphodiesterase type 5 inhibitor, potentiated the
      scratching behavior by CQ. This study therefore shows that CQ-induced scratching
      behavior is mediated by the NO/cGMP pathway. 

PMID- 25957524
TI  - Embelin lipid nanospheres for enhanced treatment of ulcerative colitis -
      Preparation, characterization and in vivo evaluation.
AB  - Aim of the present study is to develop embelin lipid nanospheres (LNE) for better
      treatment of ulcerative colitis. Embelin LNs were developed using soya bean
      oil/virgin coconut oil as liquid lipid carrier and soya/egg lecithin as
      stabilizer by hot homogenization followed by ultrasonication technique. The
      particle size of LNEs ranged from 196.1+/-3.57 to 269.2+/-1.05nm with narrow
      polydispersity index values whereas zeta potential was from -36.6 to -62.0mV.
      Embelin was successfully incorporated into lipid nanospheres with entrapment
      efficiency about 99%. There was no interaction between embelin and selected
      liquid lipids which was confirmed by FTIR studies. In vitro drug release studies
      performed using Franz diffusion cell and results showed sustained release of
      embelin. Embelin LNs were stabilized with egg and soya lecithin, embelin release
      from these LNs followed Higuchi model and first order model, respectively,
      however mechanism of drug release in both LNs was non-Fickian. In vivo studies
      were carried out using acetic acid induced ulcerative colitis rat model and
      results revealed that treatment with embelin LNs significantly reduced clinical
      activity and macroscopic scores compared to embelin conventional suspension.
      Treatment with embelin LNs decreased MPO, LDH and LPO levels, increased reduced
      GSH levels which indicated better treatment of ulcerative colitis was achieved.
      This was also confirmed by improved histopathological conditions. Thus embelin
      LNs could be favourably used for treatment of ulcerative colitis. 

PMID- 25957527
TI  - Measurement of unlabeled and stable isotope-labeled homoarginine, arginine and
      their metabolites in biological samples by GC-MS and GC-MS/MS.
AB  - Circulating and excretory L-homoarginine (hArg) and asymmetric dimethylarginine
      (ADMA) are cardiovascular risk factors. L-Arginine (Arg) is the common precursor
      of hArg and ADMA. This protocol describes gas chromatography-mass spectrometry
      (GC-MS) and gas chromatography-mass spectrometry-mass spectrometry (GC-MS/MS)
      methods for the quantitative determination of hArg, Arg and ADMA in biological
      samples, including human plasma, urine and sputum. Aliquots (10 uL) of native
      urine, plasma or serum ultrafiltrate (cutoff, 10 kDa), and acetone-deproteinized
      sputum samples are evaporated to dryness. Then, amino acids are derivatized to
      their methyl ester N-pentafluoropropionyl derivatives. In parallel,
      trideuteromethyl ester N-pentafluoropropionyl derivatives of hArg, Arg and ADMA
      are de novo synthesized from the unlabelled amino acids and used as internal
      standards. Alternatively, commercially available stable isotope-labeled analogs
      of hArg, Arg and ADMA are used as internal standards, and they are added to the
      native biological samples. Quantification is performed by selected ion monitoring
      in GC-MS and selected reaction monitoring in GC-MS/MS. By these protocols,
      unlabelled and stable isotope-labeled hArg, Arg and their metabolites including
      ADMA and ornithine can be measured equally accurately and precisely by GC-MS and
      GC-MS/MS in several different biological fluids in experimental and clinical
      settings.

PMID- 25957528
TI  - Taurine increases testicular function in aged rats by inhibiting oxidative stress
      and apoptosis.
AB  - In males, the decline of androgen synthesis, spermatogenesis and sexual function
      are the main phenotypes of aging, which may be attributed to testicular
      dysfunction. Taurine can act as an antioxidant, a testosterone secretion
      stimulator, a sperm membrane stabilizer and motility factor, and an anti
      apoptotic agent. Recent observational studies suggested that taurine may play an
      important role in spermatogenesis, but to date whether taurine has anti-aging
      effects on testes remains unknown. We found that in aged rats testicular SDH and
      G6PDH activities, marker enzymes of testes, serum testosterone, testicular 3beta
      HSD and 17beta-HSD mRNA expression levels were significantly increased by taurine
      treatment. Taurine administration also markedly raised the sperm count, viability
      and motility, decreased the sperm abnormality. Our data suggested that taurine
      can postpone testicular function deterioration in aged rats. Importantly, we
      observed obvious elevation of testicular antioxidant enzymes (SOD, GSH, GSH-Px)
      activities, and remarkable reduction of ROS and MDA by taurine administration,
      indicating taurine can decrease testicular oxidative stress and lipid
      peroxidation in aged rats. Finally, we found taurine effectively reduced
      testicular DNA fragmentation, increased testicular Bcl-2 protein expression, and
      decreased cytochrome c, Bax, Fas, FasL and caspase-3 expression, suggesting
      taurine can prohibit aged testicular apoptosis by mitochondrial dependent and
      independent signal pathway. In summary, our results indicated that taurine can
      suppress testicular function deterioration by increasing antioxidant ability and
      inhibiting apoptosis. 

PMID- 25957530
TI  - Case report of a guide wire loss and migration after central venous access.
AB  - We report a case of guide wire loss and migration after central venous access for
      spinal deformity surgery. Guide wire migration was noticed on a follow-up full
      spine x-ray 69 days postoperatively. Percutaneous retrieval was successfully
      performed using endovascular techniques. With this case report, we want to
      highlight the fact that one could miss other pathologies visible on these full
      spine x-rays when concentrating only on the measurement of spinopelvic
      parameters.

PMID- 25957526
TI  - Diabetes and Behavioral Learning Principles: Often Neglected yet Well-Known and
      Empirically Validated Means of Optimizing Diabetes Care Behavior.
AB  - Managing diabetes is known to be invasive, pervasive, and unrelenting, making
      adherence to the treatment regimen difficult to accomplish. Ongoing clinical and
      research efforts have attempted to address the struggles faced by youth and
      adults with diabetes. Recent research supports the integration of behavioral
      interventions into clinical practice to assist patients and families with the
      goal of improving health outcomes. Empirically supported and well-documented
      behavioral learning principles, particularly positive reinforcement, are often
      underutilized in modern diabetes care. We posit that most diabetes care providers
      are aware of these principles. However, the constraints of today's medical
      systems have become significant barriers to purposefully and consistently
      applying them to promote improved diabetes care. We provide a brief overview of
      basic behavioral principles and common barriers to implementation, discuss
      relevant interventions, and present several examples of applications in clinical
      settings. We conclude with recommendations to raise awareness regarding the
      importance of consistently integrating relevant behavioral learning principles
      and interventions into diabetes care settings. 

PMID- 25957534
TI  - The effect of pattern overlap on the accuracy of high resolution electron
      backscatter diffraction measurements.
AB  - High resolution, cross-correlation-based, electron backscatter diffraction (EBSD)
      measures the variation of elastic strains and lattice rotations from a reference
      state. Regions near grain boundaries are often of interest but overlap of
      patterns from the two grains could reduce accuracy of the cross-correlation
      analysis. To explore this concern, patterns from the interior of two grains have
      been mixed to simulate the interaction volume crossing a grain boundary so that
      the effect on the accuracy of the cross correlation results can be tested. It was
      found that the accuracy of HR-EBSD strain measurements performed in a FEG-SEM on
      zirconium remains good until the incident beam is less than 18 nm from a grain
      boundary. A simulated microstructure was used to measure how often pattern
      overlap occurs at any given EBSD step size, and a simple relation was found
      linking the probability of overlap with step size.

PMID- 25957532
TI  - Ten years of subproteome investigations in lactic acid bacteria: A key for food
      starter and probiotic typing.
AB  - The definition of safety and efficacy of food-employed bacteria as well as
      probiotic strains is a continuous, often unattended, challenge. Proteomic
      techniques such as 2DE, DIGE and LC/LC-MS/MS are suitable and powerful tools to
      reveal new aspects (positive and negative) of "known" and "unknown" strains that
      can be employed in food making and as nutraceutical supplements for human health.
      Unfortunately, these techniques are not used as extensively as it should be wise.
      The present report describes the most significant results obtained by our
      research group in 10years of study on subproteomes in bacteria, chiefly lactic
      acid bacteria. Production of desired and undesired metabolites, differences
      between strains belonging to same species but isolated from different ecological
      niches, the effect of cryoprotectants on survival to lyophilization as well as
      the adhesive capability of strains, were elucidated by analysis of cytosolic,
      membrane-enriched, surface and extracellular proteomes. The present review opens
      a window on a yet largely underexplored field and highlights the huge potential
      of subproteome investigations for more rational choice of microbial strains as
      food starters, probiotics and for production of nutraceuticals. These analyses
      will hopefully contribute to manufacturing safer and healthier food and food
      supplements in the near future. This article is part of a Special Issue entitled:
      HUPO 2014. 

PMID- 25957531
TI  - Adjusting for Baseline Covariates in Net Benefit Regression: How You Adjust
      Matters.
AB  - BACKGROUND AND OBJECTIVE: The literature has shown that different baseline
      adjustment approaches lead to different results when examining cost and quality
      adjusted life-years. To our knowledge, the concept of baseline adjustment in a
      net benefit (NB) regression has not been studied. The purpose of the study was to
      explore the impact of different baseline adjustment approaches in an NB framework
      on the cost effectiveness of an intervention using person-level data. METHODS:
      This study used data from a randomized controlled trial that evaluated the
      effectiveness of a multifactorial falls prevention intervention for older home
      care clients. The outcome was the number of falls at the 6-month follow-up. The
      cost variable was the total healthcare costs from a societal perspective.
      Incremental NB values were estimated using four baseline adjustment approaches:
      (1) the change in NB is the dependent variable; (2) the NB at follow-up is the
      dependent variable without adjusting for baseline values; (3) the NB at follow-up
      is the dependent variable adjusting for baseline NB; and (4) the NB at follow-up
      is also the dependent variable adjusting for baseline cost and effect separately.
      RESULTS: With adjustment of baseline values (Approach 1, 3, 4), the intervention
      was not cost effective when compared to usual care. Conversely, without baseline
      adjustment (Approach 2), the intervention was cost effective if decision-makers'
      willingness-to-pay per fall prevented was CAN$10,000 or greater. CONCLUSIONS:
      This study showed that different baseline adjustment approaches in a cost
      effectiveness analysis can lead to different results. Future research is needed
      to determine the most appropriate adjustment approach in planning economic
      evaluation using NB regression.

PMID- 25957529
TI  - Single-injection thoracic paravertebral block and postoperative analgesia after
      mastectomy: a retrospective cohort study.
AB  - BACKGROUND: The treatment of postoperative pain after mastectomy is an area of
      increasing interest, as this treatment option is now considered a standard of
      care for those affected by breast cancer. Thoracic paravertebral nerve block
      (tPVB) using local anesthetics administered before mastectomy can theoretically
      provide postoperative analgesia, thereby facilitating a more comfortable and
      shorter hospitalization. METHODS: In this retrospective cohort study, we aimed to
      determine the duration and degree to which tPVB provides postoperative analgesia
      in patients who underwent either unilateral or bilateral mastectomy (n = 182). We
      retrospectively examined the numeric rating scale (NRS) for pain scores recorded
      by nursing staff throughout individual patient hospitalizations, looking
      specifically at the following time points: arrival from the postanesthesia care
      unit to the surgical wards, noon on postoperative day 1 (POD1), and discharge. We
      also examined the number of days until patients were discharged from the
      hospital. RESULTS: Our results revealed a statistically significant decrease in
      NRS in pain scores for patients who had received a tPVB (n = 92) on arrival from
      the postanesthesia care unit to the surgical wards (mean NRS decrease of 1.9
      points; 99% confidence interval [CI], -3.0 to -0.8; P < .001) but did not show
      statistically significant decreases in NRS for pain scores for patients at noon
      on POD1 (mean NRS decrease of 0.3 points at noon on POD1, P = .43) or at
      discharge (mean NRS decrease of 0.1 point at discharge, P = .65). Moreover, use
      of tPVB did not have an impact on time until discharge (average decrease of 0.5
      hours; 95% CI, -6 to +5 hours, P = .87). CONCLUSIONS: Single-injection tPVB
      appears to provide meaningful postoperative analgesia in the immediate
      postoperative period after mastectomy but not after the first day of surgery.

PMID- 25957533
TI  - Quantitative proteomic analysis of the cellulolytic system of Clostridium
      termitidis CT1112 reveals distinct protein expression profiles upon growth on
      alpha-cellulose and cellobiose.
AB  - Clostridium termitidis CT1112 is an anaerobic, mesophilic, cellulolytic bacterium
      with potential applications in consolidated bioprocessing of lignocellulosic
      biomass. To understand how C. termitidis degrades lignocellulose, iTRAQ-based 2D
      HPLC-MS/MS proteomics was used to measure protein expression in cell lysates and
      extracellular (secretome) fractions of C. termitidis grown on alpha-cellulose and
      cellobiose at both exponential and stationary growth phases. Exoglucanases (GH48,
      GH9), endoglucanases (GH5, GH8, GH9), hemicellulases including xylanases (GH8,
      GH10, GH11, GH30) and mannanase (GH26) as well as extracellular adhesion proteins
      and cellulosome associated proteins, exhibited higher expression on cellulose
      grown cells. The expression of these proteins increased with a decrease in growth
      rate. Non-cellulosomal proteins however did not change significantly between
      substrate conditions, although there were a few exceptions. Collectively, these
      would contribute to hydrolysis of lignocellulosic material for uptake through ABC
      sugar transport proteins. On cellobiose, chitinases (GH18) were expressed
      abundantly. Although a large number of proteins were shared between the fractions
      analyzed, some proteins were detected exclusively in the cellular fraction, while
      others were detected in the secretome. This study reports for the first time on
      the cellulolytic machinery employed by C. termitidis to hydrolyze cellulosic
      substrate and provides an understanding of how this microbe deconstructs biomass.
      BIOLOGICAL SIGNIFICANCE: The genome of C. termitidis CT1112 contains genes for a
      wide variety of carbohydrate active enzymes. Based on bioinformatics analyses,
      many of these genes appear to encode cellulosome-associated proteins, while
      others may be secreted extracellularly. To understand how C. termitidis degrades
      and depolymerizes cellulosic substrates, cells were grown on simple and complex
      carbohydrates, and quantitative 4-plex iTRAQ-based 2D HPLC-MS/MS proteomics was
      applied to measure protein expression levels in biological replicates of both
      cell lysates and extracellular protein (secretome) fractions, at exponential and
      stationary phases of growth. The resulting data have provided insight into the
      range of substrates that may be hydrolyzed by C. termitidis, and may be useful in
      determining potential industrial applications of C. termitidis in biomass to
      bioenergy production via consolidated bioprocessing.

PMID- 25957525
TI  - The evolving understanding of the contribution of lipid metabolism to diabetic
      kidney disease.
AB  - Although diabetes is mainly diagnosed based on elevated glucose levels,
      dyslipidemia is also observed in these patients. Chronic kidney disease (CKD), a
      frequent occurrence in patients with diabetes, is associated with major
      abnormalities in circulating lipoproteins and renal lipid metabolism. At
      baseline, most renal epithelial cells rely on fatty acids as their energy source.
      CKD, including that which occurs in diabetes, is characterized by tubule
      epithelial lipid accumulation. Whether this is due to increased uptake or greater
      local fatty acid synthesis is unknown. We have recently shown that CKD also leads
      to decreased fatty acid oxidation, which might be an additional mechanism leading
      to lipid accumulation. Defective fatty acid utilization causes energy depletion
      resulting in increased apoptosis and dedifferentiation, which in turn contributes
      to fibrosis and CKD progression. Enhanced fatty acid oxidation in the kidney
      induced by fenofibrate, a peroxisomal proliferator-activated receptor (PPAR)
      alpha agonist, showed benefit in mouse models of CKD. Fenofibrate treatment also
      reduced albuminuria in patients with diabetes in multiple clinical trials. Taken
      together, these findings suggest that further understanding of lipid metabolism
      in diabetic kidney disease may lead to novel therapeutic approaches. 

PMID- 25957535
TI  - Idiopathic ankylosis of lumbar spine after nonfusion surgery.

PMID- 25957539
TI  - A case of symptomatic cervical spine calcinosis in systemic sclerosis.

PMID- 25957538
TI  - Post-traumatic cervical nerve root avulsion: direct and indirect magnetic
      resonance myelography findings.

PMID- 25957536
TI  - Spinal cord stimulation: a review of the safety literature and proposal for
      perioperative evaluation and management.
AB  - BACKGROUND CONTEXT: There is currently no consensus on appropriate perioperative
      management of patients with spinal cord stimulator implants. Magnetic resonance
      imaging (MRI) is considered safe under strict labeling conditions. Electrocautery
      is generally not recommended in these patients but sometimes used despite known
      risks. PURPOSE: The aim was to discuss the perioperative evaluation and
      management of patients with spinal cord stimulator implants. STUDY DESIGN: A
      literature review, summary of device labeling, and editorial were performed,
      regarding the safety of spinal cord stimulator devices in the perioperative
      setting. METHODS: A literature review was performed, and the labeling of each
      Food and Drug Administration (FDA)-approved spinal cord stimulation system was
      reviewed. The literature review was performed using PubMed and the FDA website
      (www.fda.gov). RESULTS: Magnetic resonance imaging safety recommendations vary
      between the models. Certain systems allow for MRI of the brain to be performed,
      and only one system allows for MRI of the body to be performed, both under strict
      labeling conditions. Before an MRI is performed, it is imperative to ascertain
      that the system is intact, without any lead breaks or low impedances, as these
      can result in heating of the spinal cord stimulation (SCS) and injury to the
      patient. Monopolar electrocautery is generally not recommended for patients with
      SCS; however, in some circumstances, it is used when deemed required by the
      surgeon. When cautery is necessary, bipolar electrocautery is recommended. Modern
      electrocautery units are to be used with caution as there remains a risk of
      thermal injury to the tissue in contact with the SCS. As with MRI, electrocautery
      usage in patients with SCS systems with suspected breaks or abnormal impedances
      is unsafe and may cause injury to the patient. CONCLUSIONS: Spinal cord
      stimulation is increasingly used in patients with pain of spinal origin,
      particularly to manage postlaminectomy syndrome. Knowledge of the safety concerns
      of SCS and appropriate perioperative evaluation and management of the SCS system
      can reduce risks and improve surgical planning.

PMID- 25957537
TI  - Modified partial pedicle subtraction osteotomy for the correction of post
      traumatic thoracolumbar kyphosis.
AB  - BACKGROUND CONTEXT: Pedicle subtraction osteotomy (PSO) is the most commonly
      recommended technique for the correction of local post-traumatic thoracolumbar
      deformity; however, the surgical results are not always satisfactory because the
      possibly damaged upper disc is preserved, and all the posterior elements are
      resected. PURPOSE: The aim was to compare the results of standard PSO and
      modified PSO in the treatment of post-traumatic thoracolumbar kyphosis. STUDY
      DESIGN: This was a retrospective multicenter comparative clinical study. PATIENT
      SAMPLE: A total of 86 patients were included in the final analysis. OUTCOME
      MEASURES: The outcome measures included local Cobb angle of the kyphosis, visual
      analog scale (VAS) score, and Oswestry disability index (ODI) score. METHODS: The
      upper disc was resected, and the inferior wall of the index pedicle and the lower
      facet joint were preserved in the modified PSO. Patients with focal kyphosis
      greater than 30 degrees  who were treated with one-level osteotomy, without the
      presence of spine neoplasm, infection, or previous surgery, were included. The
      measurements included the VAS score, ODI score, and preoperative and
      postoperative Cobb angles. RESULTS: Forty-two patients in the modified PSO group
      and 44 in the standard PSO group were included in the final analysis. The mean
      surgical time and blood loss were similar between the two groups. Both the VAS
      and ODI scores had improved significantly at the final follow-up in the two
      groups. The mean Cobb angle significantly improved from 39.6 degrees  to 5.6
      degrees  in the modified PSO group and from 39.1 degrees  to 4.8 degrees  in the
      standard PSO group, with no significant difference between the two groups
      preoperatively or at the final follow-up. CONCLUSIONS: The modified PSO provides
      an alternative method with which to correct kyphotic deformity in patients with
      post-traumatic thoracolumbar kyphosis.

PMID- 25957540
TI  - Spinal Schwannoma presenting due to torsion and hemorrhage: case report and
      review of literature.
AB  - BACKGROUND CONTEXT: The presentation of a tumor due to torsion, with hemorrhage
      from presumed reperfusion injury as a result of infarction of the lesion, is
      extremely rare and may be different than typical tumor presentation. PURPOSE: The
      aim was to describe a patient with a rare case of twisted intradural nerve sheath
      myxoid Schwannoma. STUDY DESIGN: This was a case report and a review of
      literature. METHODS: A patient presented with acute onset of severe pain was
      found to have minimally enhanced intradural extramedullary cystic lesion. The
      patient underwent bilateral L2 and L3 laminectomy and microsurgically assisted
      intradural exploration. RESULTS: At laminectomy and intradural exploration, it
      was found to be a Schwannoma, which had rotated above and below, with obvious
      color change consistent with either infarction or hemorrhage. Because the color
      change ceased abruptly at the site of the torsion, we presumed that the mechanism
      of the hemorrhage in and around the Schwannoma found at pathologic evaluation was
      due to the torsion. The torsion caused vascular insufficiency (likely venous) and
      produced subsequent reperfusion-related hemorrhage, because of the compression of
      the vascular supply coming from the proximal and distal ends of the root of
      origin. The patient did well with complete resolution of his symptoms and 11
      years of pain relief. CONCLUSIONS: This acute infarction of the tumor and the
      associated nerve caused the acute pain syndrome that is not commonly associated
      with lumbar Schwannomas. Patients with acute onset of severe radiating pain may
      have torsion of a benign tumor arising from the nerve in question.

PMID- 25957541
TI  - Participation of hMLH1, p63, and MDM2 proteins in the pathogenesis of syndromic
      and nonsyndromic keratocystic odontogenic tumors.
AB  - OBJECTIVES: To evaluate the expression of hMLH1, p63, and MDM2 in Gorlin syndrome
      associated keratocystic odontogenic tumors (SKOTs) and nonsyndromic keratocystic
      odontogenic tumors (NSKOTs). STUDY DESIGN: Seventeen primary NSKOTs, 17 SKOTs,
      and 8 recurrent NSKOTs were analyzed by using immunohistochemistry. RESULTS: No
      significant differences in the hMLH1, p63, or MDM2 labeling indices were observed
      between groups (P = .398; P = .232; P = .426, respectively). Higher hMLH1
      immunoexpression was found in the basal layer of primary NSKOTs. Most KOTs
      exhibited p63 immunoexpression in the upper layers of the epithelium. MDM2
      immunoexpression was observed in the upper epithelial layers of SKOTs and
      recurrent NSKOTs. CONCLUSION: It was not possible to correlate the
      immunoexpression of hMLH1, p63, and MDM2 in SKOTs and primary and recurrent
      NSKOTs, suggesting that these proteins exert independent effects on the
      development of these groups of tumors.

PMID- 25957542
TI  - Effect of Kaempferia parviflora Extract on Physical Fitness of Soccer Players: A
      Randomized Double-Blind Placebo-Controlled Trial.
AB  - BACKGROUND: Physical fitness is a fundamental prerequisite for soccer players.
      Kaempferia parviflora is an herbal plant that has been used in some Asian
      athletes with the belief that it might prevent fatigue and improve physical
      fitness. This study aimed to determine the effects of Kaempferia parviflora on
      the physical fitness of soccer players. MATERIAL AND METHODS: Sixty soccer
      players who routinely trained at a sports school participated in a double-blind
      placebo-controlled trial and were randomly allocated to the treatment group or
      the placebo group. The participants in both groups were given either 180 mg of
      Kaempferia parviflora extract in capsules or a placebo once daily for 12 weeks.
      Baseline data were collected using the following 6 tests of physical performance:
      a sit-and-reach test, a hand grip strength test, a back-and-leg strength test, a
      40-yard technical test, a 50-metre sprint test, and a cardiorespiratory fitness
      test. All of the tests were performed every 4 weeks throughout the 12-week study
      period. RESULTS: The study showed that after treatment with Kaempferia
      parviflora, the right-hand grip strength was significantly increased at weeks 4,
      8, and 12. The left-hand grip strength was significantly increased at week 8.
      However, the back-and-leg strength, the 40-yard technical test, the sit-and-reach
      test, the 50-metre sprint test, and the cardiorespiratory fitness test results of
      the treatment group were not significantly different from those of the placebo
      group. CONCLUSIONS: Taking Kaempferia parviflora supplements for 12 weeks may
      significantly enhance some physical fitness components in soccer players.

PMID- 25957544
TI  - Does a brace influence clinical outcomes after arthroscopic rotator cuff repair?
AB  - PURPOSE: The goal of this study was to report the clinical effects of two
      different braces after rotator cuff repair. METHODS: Forty patients who underwent
      an arthroscopic rotator cuff repair were prospectively allocated in this study.
      Twenty patients were immobilized in 15 degrees  external rotation brace (ER
      Group), and twenty were immobilised in an internal rotation sling (IR Group). For
      all patients, four surveys were done: in the immediate pre-operative period (T0),
      at 1 month (T1), at 3 months (T2) and at 6 months after surgery (T3). Range of
      motion and pain were evaluated by an independent physician. Self-Assessment
      Scales [(University California Los Angeles Shoulder Rating Scale (UCLA),
      Disability of the Arm Shoulder and Hand (DASH), Visual Analog Scale (VAS), Simple
      Shoulder Test (SST) and Physician Assessment Scale (Constant)] were also
      administered. RESULTS: Abduction and ER2 (external rotation with arm in
      abduction) were significantly greater in the ER group at T1, T2 and T3, ER1
      (external rotation with arm at side) was significantly greater in the ER group at
      T1 and T2, IR2 (internal rotation) was significantly greater in the ER group at
      T1, and FFL (forward flexion) was significantly greater in the ER group at T1.
      VAS was significantly lower in the ER group at T1 and T2 and T3. About the Self
      Assessment Shoulder Scales after 3 and 6 months, no differences were found. SST
      showed a lesser functional limitation for the ER group at T3. CONCLUSIONS:
      Patients operated with isolated superior or posterosuperior rotator cuff tear
      immobilised with brace in 15 degrees  of ER position showed less pain and a
      better passive range of motion at short time after surgery.

PMID- 25957543
TI  - Intramedullary clavicle fixation with single large fragmentary screw.
AB  - BACKGROUND: The treatment of clavicle fractures has historically been
      nonoperative, but several studies have recently shown the merits of operative
      management for specific fractures patterns. We developed a novel technique
      utilizing a 6.5-mm cannulated screw for fixation of displaced midshaft clavicle
      fractures. MATERIALS AND METHODS: We present 15 consecutive patients treated with
      this technique between 2007 and 2012. All patients were male, and all 15 suffered
      a traumatic injury involving a fall directly onto the affected side. Mean time
      from injury to surgery was 12 days (range 3-24 days). Decision for surgery was
      based on the displacement and shortening of the fracture, either at least 20 mm
      of shortening or displacement with no bony apposition. After surgery, all
      patients were placed in an abduction brace for 6 weeks. No motion was allowed for
      the first 3 weeks, followed by passive shoulder motion below 90 degrees  of
      forward flexion under the supervision of a therapist for the next 3 weeks.
      RESULTS: All 15 patients progressed to union at an average of 5.7 months (range 3
      12). Three patients had superficial wound infections. Hardware removal was
      performed in 6 of the 15 patients at an average of 12 months (range 5-24). All
      patients regained full range of motion and strength in comparison with
      contralateral extremity. CONCLUSION: This novel technique limits soft tissue
      stripping. It has the advantages of using an implant familiar to most
      orthopedists and available in most hospital settings. We believe this technique
      is ideally suited for transverse fractures patterns, less than 14 days old, in
      males greater than 180 cm with clavicles large enough to accommodate a 6.5-mm
      screw.

PMID- 25957545
TI  - Complex proximal humerus fractures: Hertel's criteria reliability to predict head
      necrosis.
AB  - BACKGROUND: The risk of post-traumatic humeral head avascular necrosis (AVN),
      regardless of the treatment, has a high reported incidence. In 2004, Hertel et
      al. stated that the most relevant predictors of ischemia after intracapsular
      fracture treated with osteosynthesis are the calcar length, medial hinge
      integrity and some specific fracture types. Based on Hertel's model, the purpose
      of this study is to evaluate both its reliability and weaknesses in our series of
      267 fractures, assessing how the anatomical configuration of fracture, the
      quality of reduction and its maintenance were predictive of osteonecrosis
      development, and so to suggest a treatment choice algorithm. MATERIALS AND
      METHODS: A retrospective study, level of evidence IV, was conducted to duly
      assess the radiographic features of 267 fractures treated from 2004 to 2010
      following Hertel's criteria treated with open reduction and internal fixation by
      angular stability plates and screws. The average age was 65.2 years. The average
      follow-up was 28.3 +/- 17.0 months. The percentage of AVN, the quality and
      maintenance of reduction obtained during surgery were evaluated. RESULTS: The AVN
      incidence was 3.7 %. No significant correlation with gender, age and fracture
      type was found. At the last follow-up X-ray, only 30 % presented all Hertel's
      good predictors in the AVN group, 4.7 % in the non-AVN group (p < 0.05). About
      quality of reduction in the AVN group, it was poor in 50 %; while in the non-AVN
      group, it was poor in 3.4 % (p < 0.05). Four patients with AVN were symptomatic,
      and three needed a second surgery. CONCLUSIONS: Hertel's criteria are important
      in the surgical planning, but they are not sufficient: an accurate evaluation of
      the calcar area fracture in three planes is required. All fractures involving
      calcar area should be studied with CT.

PMID- 25957546
TI  - Triceps tendon rupture: the knowledge acquired from the anatomy to the surgical
      repair.
AB  - Triceps injuries are relatively uncommon in most traumatic events, and the distal
      triceps tendon ruptures are rare. Recently, the knowledge of this tendon lesion
      has increased, and it seems to be related to more precise diagnostic and clinical
      assessments. The most common mechanism of injury remains a forceful eccentric
      contraction of the muscle, while several other risk factors have been studied as
      chronic renal failure, endocrine disorders, metabolic bone diseases as well as
      steroid use. Olecranon bursitis and local corticosteroid injections may also play
      a role. The commonest site of rupture is at the tendon's insertion into the
      olecranon and rarely at the myotendinous junction or intramuscularly. The
      surgical intervention is recommended in acute complete ruptures, and non
      operative treatment is reserved for patients with major comorbidities, as well as
      for partial ruptures with little functional disability and in low demanding
      patients. Various techniques and approaches as the direct repair to bone, the
      tendon augmentation, the anconeus rotation flap and the Achilles tendon allograft
      have been proposed for the management of these challenging injuries. The goal of
      surgical management should be an anatomical repair of the injured tendon by
      selection of a procedure with a low complication rate and one that allows early
      mobilization. This manuscript focuses the triceps tendon ruptures starting from
      the anatomy to the diagnosis and entity of the triceps tendon injuries, as well
      as the indications and guidelines for the management. 

PMID- 25957547
TI  - Short- to mid-term follow-up effectiveness of US-guided focal extracorporeal
      shock wave therapy in the treatment of elbow lateral epicondylitis.
AB  - BACKGROUND: Lateral epicondylitis of the elbow is a common and disabling overuse
      syndrome. Several treatment modalities are currently available for this
      condition, but the optimal treatment method remains undefined. Extracorporeal
      shock wave therapy (ESWT) has been widely used in the last 10 years, although
      conflicting results are present in the literature. MATERIALS AND METHODS: In this
      study, we evaluated 36 patients (37 elbows), with a mean follow-up time of 24.8
      months. Focal ESWT was administered by means of an electromagnetic generator
      equipped with in-line ultrasound guidance, during one or more cycles of 3-4
      weekly sessions. In the setting of the study, patients were clinically evaluated
      and subjective satisfaction and rate of relapse were investigated. RESULTS: A
      positive response was described in 75.7 % of the patients after treatment. Mean
      quickDASH score and VAS attested at 5.5 and 1.1, respectively. Roles and Maudsley
      score was rated as I or II in 33 cases. Four patients resulted not responders to
      the therapy, while 5 patients complained one or more episodes of symptoms
      relapse. No influence on the final outcome was evident with respect to
      demographic features and previous therapies as well. Response rate to further
      ESWT cycles in patients refractory to the first cycle of ESWT was 33.3 %.
      CONCLUSIONS: Focal ESWT represents a valuable and safe solution in case of elbow
      lateral epicondylitis, both in newly diagnosed and previously treated cases,
      representing a definitive treatment in the majority of patients. Patients
      refractory to a 3- to 4-session ESWT cycle have lower chances of positive
      response after further ESWT cycles.

PMID- 25957548
TI  - Outcomes after surgical treatment of missed Monteggia fractures in children.
AB  - BACKGROUND: Chronic dislocation of the radial head treatment in Monteggia
      fracture dislocation is still controversial. We present a large series of
      patients treated in our Institution. MATERIALS AND METHODS: The outcome of 22
      children treated surgically between 1988 and 2011 for post-traumatic chronic
      radial head dislocation is reported. There were 12 girls and 10 boys with a mean
      age at surgery of 7.2 years (4.1-13.6). The mean interval between injury and
      treatment was 15.7 months (1-128). Nine patients underwent open reduction with
      removal of interposed tissue and repair (7) or Bell-Tawse reconstruction (2) of
      the annular ligament. Ten patients underwent osteotomy, gradual lengthening and
      angulation of the ulna by external fixation. Two patients underwent angular
      osteotomy of the proximal ulna with open wedge, open reduction in the radial head
      and reconstruction of the annular ligament. One patient admitted to the hospital
      10 years after injury underwent radial head excision at 13.7 years of age.
      RESULTS: After a mean follow-up of 5.5 years (1-24.3), the radial head stayed
      reduced in 15 patients and subluxated in 5. In one case, redislocation occurred.
      All patients but five were pain-free. The elbow performance score (Kim score) was
      excellent in 14 cases, good in four and fair in four, with a mean score of 91,
      corresponding to a good result. Complications included a transient posterior
      interosseus nerve palsy (1), and one non-union of the ulna. DISCUSSION AND
      CONCLUSION: Chronic Monteggia lesions must be treated. The clinical outcomes are
      usually better than the congruency of the radiocapitellar joint.

PMID- 25957549
TI  - Co-analgesic therapy for arthroscopic supraspinatus tendon repair pain using a
      dietary supplement containing Boswellia serrata and Curcuma longa: a prospective
      randomized placebo-controlled study.
AB  - BACKGROUND: The cuff tendon that is most prone to full-thickness rotator cuff
      tears is the supraspinatus (SSP). Arthroscopic SSP repair ensures good to
      satisfactory mid- to long-term clinical outcomes. However, the intense
      postoperative pain reduces rehabilitation compliance and is cause of patient
      dissatisfaction. Many natural compounds act by inhibiting inflammatory pathways
      in a similar way to anti-inflammatory drugs MATERIALS AND METHODS: This was a
      prospective randomized trial designed to assess the analgesic effect of a dietary
      supplement (DS) containing Boswellia serrata and Curcuma longa in a population of
      subjects with full-thickness SSP tendon tear treated by arthroscopy. Three weeks
      before surgery, patients were randomized to receive Tendisulfur((r)) (group T) or
      a placebo (group P) for 2 months. The primary outcome measure was subjective VAS
      pain. Secondary outcomes measures were Constant-Murley score simple shoulder
      test, and patient global assessment (PGA) scores. Patients were assessed
      immediately at baseline and subsequently at 1, 2, 4, 6, 8, 12, and 24 weeks.
      RESULTS: Stratification of pain scores and subscores demonstrated significantly
      lower overall pain scores in group T versus group P at 1 week (p = 0.0477), and
      lower but not significantly different scores on week 2 (p = 0.0988); at
      subsequent time points, differences were not significant (p > 0.05). PGA scores
      were good in all subjects. CONCLUSIONS: In conclusion, this study provides
      objective data on the effect of a DS containing natural substances, added to
      standard analgesics, on postoperative RC pain. DS alleviated short and partially
      mid-term pain, while long-term pain was unchanged. This limitation can probably
      be addressed by a dosage increase over the first 4 weeks and by extending
      treatment by 1 or 2 months.

PMID- 25957554
TI  - Experimental therapies in the neuronal ceroid lipofuscinoses.
AB  - The neuronal ceroid lipofuscinoses represent a group of severe childhood
      lysosomal storage diseases. With at least 13 identified variants they are the
      most common cause of inherited neurodegeneration in children. These diseases
      share common pathological characteristics including motor problems, vision loss,
      seizures, and cognitive decline, culminating in premature death. Currently, no
      form of the disease can be treated or cured, with only palliative care to
      minimise discomfort. This review focuses on current and potentially ground
      breaking clinical trials, including small molecule, enzyme replacement, stem
      cell, and gene therapies, in the development of effective treatments for the
      various disease subtypes. This article is part of a Special Issue entitled:
      "Current Research on the Neuronal Ceroid Lipofuscinoses (Batten Disease)". 

PMID- 25957551
TI  - Transphyseal elbow fracture in newborn: review of literature.
AB  - Transphyseal elbow fracture is a rare entity in newborns, and in the last
      century, only case reports or small case series have been published; however,
      precise epidemiological data lack. Such fractures occur more often in emergency
      Caesarian section or vaginal delivery. The differential diagnosis with elbow
      dislocation can be challenging. Radiography, arthrography, magnetic resonance,
      ultrasound or a combination of these have already been described to make
      diagnosis, but guidelines for the management of this injury in the neonate are
      not well established. A review of the literature of the last century about distal
      transphyseal fracture of the humerus in newborns was performed. A bibliographic
      search was conducted accessing usual medical databases. The work-up methods,
      treatments, results at follow-up and the rate of complications were collected.
      Twenty case reports or small retrospective case series reporting a total of 33
      cases were included. A posteromedial displacement of the radioulnar complex was
      found in 21 elbows (64 %). Four patients (12 %) underwent surgical treatment,
      whilst 29 (88 %) were managed without surgery. An attempt of reduction was
      reported in 23 cases (69 %). At follow-up, 88 % recovered completely the carrying
      angle and 80 % range of motion. A relationship between the type of treatment
      (conservative or surgical, with attempt of reduction or not) and results at
      follow-up could not be demonstrated. The most common complication was cubitus
      varus. Transphyseal elbow fractures are rare among newborns. Regardless of the
      treatment choice, such lesions are in most cases associated with a good
      prognosis.

PMID- 25957553
TI  - Nail-preserving modified lateral subperiosteal approach for subungual glomus
      tumour: a novel surgical approach.
AB  - PURPOSE: Glomus tumours are benign, vascular neoplasms arising from glomus body
      and are often found near the fingertips. Complete surgical excision of the tumour
      must be ensured to avoid its recurrence. Several surgical approaches for its
      excision have been described in the literature; however, most of the approaches
      are associated with nail deformity in the post-operative period or fail to offer
      a complete exposure of the tumour. We wish to share our experience with our
      described nail-preserving modified lateral subperiosteal approach, where on
      account of the distal curve over the pulp tip, we achieve a large flap yielding
      an excellent exposure of the tumour mass. METHODS: We retrospectively evaluated
      30 patients with subungual glomus tumour who were operated using this approach at
      a mean follow-up of 35.33 months. All patients were assessed for relief in the
      pre-operative symptoms, nail deformity, recurrence or any other complications.
      RESULTS: All wounds healed well without any possible wound complications such as
      wound dehiscence, suture margin necrosis or infection. At the end of the follow
      up, all patients were relieved of the pre-operative symptoms. There was no
      evidence of deformity of nail or fingertip. No patient had recurrence. All the
      operated fingers were functionally normal. CONCLUSIONS: Nail-preserving modified
      lateral subperiosteal approach does not damage the nail bed or interosseous
      supports to the distal phalanx. It is a very simple, less time-consuming approach
      for the resection of subungual tumours, and we would like to recommend it to our
      fellow orthopaedic surgeons.

PMID- 25957550
TI  - Arthroscopic joint debridement and capsular release in primary and post-traumatic
      elbow osteoarthritis: a retrospective blinded cohort study with minimum 24-month
      follow-up.
AB  - BACKGROUND: Elbow osteoarthritis (OA) is a degenerative condition which in the
      advanced stage can severely impair joint mobility. Conservative treatment remains
      the first choice; surgery should be considered in case of failure in patients
      prepared to adhere to a demanding rehabilitation protocol. We assess the
      effectiveness of arthroscopic joint debridement and capsular release in a series
      of patients with primary and post-traumatic elbow arthritis. MATERIALS AND
      METHODS: Forty-eight subjects (40 males, eight females; mean age 48 years) with a
      preoperative diagnosis of primary (19, 40 %) or post-traumatic OA (29, 60 %) were
      evaluated at a mean follow-up of 44 months. Outcome measures were active range of
      motion (ROM), pain score, Oxford elbow score (OES), and Mayo elbow performance
      score (MEPS). OA severity was graded into three classes (I-III) based on X-ray
      findings. Statistical significance was set at 5 %. RESULTS: At the final follow
      up evaluation, active flexion/extension increased significantly (p < 0.01);
      pronation and supination improved, but the difference was not significant (p >
      0.05). The pain score improved from 7.2 to 4.3 (p < 0.01). Both OES and MEPS
      improved significantly (p < 0.001). Patients with post-traumatic OA had better
      ROM (p = 0.0391) and clinical scores (OES, p = 0.011; MEPS, p = 0.010). ROM and
      clinical scores were lower but not significantly so in class II than in class I
      patients. A smooth coronoid and olecranon fossa was found in 38 (79 %) patients
      and a preserved ulnotrochlear joint space in 40 (80 %). CONCLUSIONS: Elbow OA has
      become more common as a result of earlier diagnosis and an increased number of
      acute injuries involving the joint. Arthroscopy is an effective technique to
      treat OA which provides the best results with the correct indications.
      Prospective studies are needed to help develop guidelines enabling selection of
      the best treatment option.

PMID- 25957552
TI  - Strength recovery after arthroscopic anterosuperior cuff repair: analysis of a
      consecutive series.
AB  - PURPOSE: The purpose of this study was to look at the functional outcomes of
      arthroscopic repair of anterosuperior rotator cuff tears. METHODS: Sixty-one
      patients who underwent arthroscopic repair of anterosuperior cuff tears were
      retrospectively reviewed. At a minimum 6 months of follow-up, shoulder functional
      outcome scores including the Constant score (CS), simple shoulder test (SST) and
      visual analogic scale (VAS) were collected. Strength recovery for supraspinatus
      and subscapularis was investigated. RESULTS: All patients (mean age 59 +/- 7)
      were available at a mean follow-up of 18 +/- 7 months. The average CS improved
      from 30.8 +/- 10.2 preoperatively to 76.5 +/- 12.0 postoperatively, average SST
      from 2.6 +/- 2.0 to 8.8 +/- 2.9 and average VAS pain scale from 3.8 +/- 1 to 0.5
      +/- 0.5 (p < 0.0001). Strength at belly-press and Jobe tests significantly
      improved (p < 0.0001). All patients with the exception of one were satisfied with
      the intervention. CONCLUSIONS: Arthroscopic repair of anterosuperior rotator cuff
      tears provides a significant improvement in pain relief and shoulder function.
      Strength recovery is demonstrated in medium correlation with tendon healing.

PMID- 25957555
TI  - Sensitization to autoimmune hepatitis in group VIA calcium-independent
      phospholipase A2-null mice led to duodenal villous atrophy with apoptosis, goblet
      cell hyperplasia and leaked bile acids.
AB  - Chronic bowel disease can co-exist with severe autoimmune hepatitis (AIH) in an
      absence of primary sclerosing cholangitis. Genetic background may contribute to
      this overlap syndrome. We previously have shown that the deficiency of iPLA2beta
      causes an accumulation of hepatocyte apoptosis, and renders susceptibility for
      acute liver injury. We here tested whether AIH induction in iPLA2beta-null mice
      could result in intestinal injury, and whether bile acid metabolism was altered.
      Control wild-type (WT) and female iPLA2beta-null (iPLA2beta(-/-)) mice were
      intravenously injected with 10mg/kg concanavalinA (ConA) or saline for 24h. ConA
      treatment of iPLA2beta(-/-) mice caused massive liver injury with increased liver
      enzymes, fibrosis, and necrosis. While not affecting WT mice, ConA treatment of
      iPLA2beta(-/-) mice caused severe duodenal villous atrophy concomitant with
      increased apoptosis, cell proliferation, globlet cell hyperplasia, and endotoxin
      leakage into portal vein indicating a disruption of intestinal barrier. With the
      greater extent than in WT mice, ConA treatment of iPLA2beta(-/-) mice increased
      jejunal expression of innate response cytokines CD14, TNF-alpha, IL-6, and SOCS3
      as well as chemokines CCL2 and the CCL3 receptor CCR5. iPLA2beta deficiency in
      response to ConA-induced AIH caused a significant decrease in hepatic and biliary
      bile acids, and this was associated with suppression of hepatic Cyp7A1, Ntcp and
      ABCB11/Bsep and upregulation of intestinal FXR/FGF15 mRNA expression. The
      suppression of hepatic Ntcp expression together with the loss of intestinal
      barrier could account for the observed bile acid leakage into peripheral blood.
      Thus, enteropathy may result from acute AIH in a susceptible host such as
      iPLA2beta deficiency. 

PMID- 25957556
TI  - 17AAG improves histological and functional outcomes in a rat CCI model through
      autophagy activation and apoptosis attenuation.
AB  - Traumatic brain injury (TBI) is caused by both primary and secondary injury
      mechanisms, all of which cause neuronal cell death and functional deficits. Both
      apoptosis and autophagy participated in neuronal cell death and functional loss
      induced following TBI. Preclinical findings implicate that 17-allylamino
      demethoxygeldanamycin (17-AAG), an anticancer drug in clinical, present
      neuroprotection actions in multiple neurological disorders, but whether 17-AAG is
      capable of modulating neuronal autophagy has never been addressed. The present
      study was designed to determine the hypothesis that17-AAG treatment could confer
      neuroprotection in a rat model of TBI. We also used an autophagy inhibitor 3
      methyladenine (3-MA) as well as an autophagy inducer rapamycin (RAPA) to test its
      underlining mechanisms. Our results showed that post-TBI administration of 17-AAG
      could attenuate brain edema, decrease neuronal death, as well as improve the
      recovery of motor function. Afterwards, in our model, 17-AAG treatment protected
      against TBI-induced apoptosis activation as well as enhanced neuronal autophagy.
      The present study provides novel clues in understanding the mechanisms of which
      17-AAG exerts its neuroprotective activity on neurological disorders. 

PMID- 25957557
TI  - Chunk decomposition contributes to forming new mental representations: An ERP
      study.
AB  - Whereas previous studies mainly focused on the role of chunk decomposition on how
      to break impasse in insight occurrence, our study aimed to investigate the role
      of chunk decomposition in forming new mental representations. For this purpose,
      the Chinese riddle comprehension task was employed in which the riddle involves
      either tight or loose chunk decomposition. The event-related potentials (ERPs)
      were measured after the onset of an answer hint, with which participants were
      instructed to comprehend the Chinese riddles. The behavioral results showed that
      participants performed worse on riddle comprehension in tight chunk condition
      than in loose chunk condition. In addition, we found larger N100 and P300
      deflections in the former condition than in the latter condition. These findings
      suggest that early perceptual processing is crucially required by chunk
      decomposition, which contributes to forming new mental representations by
      integrating the perceptual and semantic information. 

PMID- 25957558
TI  - Alterations in the blood-spinal cord barrier in TDP-43 conditional knockout mice.
AB  - We investigated whether the loss of motor neuron-specific TDP-43 protein causes
      any change in the blood-spinal cord barrier (BSCB) in the spinal cord of TDP-43
      conditional knockout (TDP CKO) mice. The TDP CKO mice were divided into four
      groups: early presymptomatic, late presymptomatic, early symptomatic, and late
      symptomatic stages. The spinal cords were pathologically examined. TDP CKO mice
      showed the activation of MAC-2 (macrophages/microglia) and fibrinogen exclusively
      in the anterior horn from the early symptomatic through the late symptomatic
      stages. Immunohistochemical and western blot analyses detected no reduction in
      tight junction proteins in TDP CKO mice as compared to age-matched wild-type mice
      at any stage. Electron-microscopically, TDP CKO mice showed vacuoles in the
      cytoplasm of most endothelial cells at the early symptomatic stage. The
      endothelium occasionally exhibited swollen cytoplasm by edematous fluid with the
      intact tight junction. The cytoplasm of the pericytes was relatively well
      preserved in contrast to the endothelial disruption. Extravascular or
      perivascular spaces were frequently edematous and vacuolated. At other stages,
      the BSCB was well preserved as in the controls. Thus, the temporary and
      reversible breakdown of the BSCB with leakage or increased permeability at the
      early symptomatic stage observed in this study could be a direct pathogenic
      consequence of the loss of TDP-43 protein, and the temporal impairment of BSCB,
      in turn, might contribute to the motor neuron degeneration in TDP CKO mice. 

PMID- 25957559
TI  - Dishevelled-2 regulates cocaine-induced structural plasticity and Rac1 activity
      in the nucleus accumbens.
AB  - Chronic cocaine exposure increases the density of dendritic spines on medium
      spiny neurons (MSNs), the predominant neuronal cell type of the nucleus accumbens
      (NAc), a key brain reward region. We recently showed that suppression of Rac1, a
      small GTPase, is a critical mediator of this structural plasticity, but the
      upstream determinants of Rac1 activity in this context remain to be elucidated.
      In this study we examined whether isoforms of Dishevelled, a key hub protein of
      multiple branches of Wnt signaling, including Rac1, are regulated in the NAc by
      chronic cocaine, and whether these Dishevelled isoforms control Rac1 activity in
      this brain region in vivo. We found that chronic cocaine administration decreased
      expression of Dishevelled-2, and several other Wnt signaling components, in the
      NAc, and that overexpression of Dishevelled-2, but not Dishevelled-1, conversely
      upregulated Rac1 activity and prevented the cocaine induction of dendritic spines
      on NAc MSNs. We posit that the cocaine-induced downregulation of Dishevelled-2 in
      the NAc is an upstream regulator of Rac1 activity and plays an important role in
      the dynamic structural plasticity of NAc MSNs seen in response to chronic cocaine
      exposure. 

PMID- 25957562
TI  - Production of transgenic beef cattle rich in n-3 PUFAs by somatic cell nuclear
      transfer.
AB  - OBJECTIVES: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are beneficial to
      human health. However, the n-3 PUFAs contents of the livestock meat that we
      consume daily are relatively low. Utilization of transgenic technology to
      increase n-3 PUFAs contents in livestock may solve this problem. RESULTS: The
      omega-3 fatty acid desaturase (FAD3), encoded by fat1 gene derived from
      Caenorhabditis elegans (C. elegans), converts omega-6 polyunsaturated fatty acids
      (n-6 PUFAs) to n-3 PUFAs. In the study, a plasmid containing the codon-optimized
      C. elegans fat1 gene (mfat1) was constructed and used to produce transgenic beef
      cattle by somatic cell nuclear transfer. Fourteen transgenic calves were
      obtained, and the ratio of n-6 to n-3 PUFAs in the transgenic calves decreased
      from 5.33: 1 to 0.95: 1 compared with negative controls. CONCLUSIONS: Our results
      demonstrated that the codon-optimized C. elegans mfat1 gene can be functionally
      expressed in the beef cattle and converts n-6 PUFAs to n-3 PUFAs.

PMID- 25957561
TI  - Direct intracerebral delivery of a miR-33 antisense oligonucleotide into mouse
      brain increases brain ABCA1 expression. [Corrected].
AB  - The ATP-binding cassette transporter A1 (ABCA1) is a membrane bound protein that
      serves to efflux cholesterol and phospholipids onto lipid poor apolipoproteins
      during HDL biogenesis. Increasing the expression and activity of ABCA1 have
      beneficial effects in experimental models of various neurologic and
      cardiovascular diseases including Alzheimer's disease. Despite the beneficial
      effects of liver X receptor (LXR) agonists--compounds that increase ABCA1
      expression--in preclinical studies, their therapeutic utility is limited by
      systemic adverse effects on lipid metabolism. Interestingly, microRNA-33 (miR-33)
      inhibition increases ABCA1 expression and activity in rodents and non-human
      primates without severe metabolic adverse effects. Herein, we demonstrate that
      treatment of cultured mouse neurons, astrocytes and microglia with an antisense
      oligonucleotide (ASO) targeting miR-33 increased ABCA1 expression, which was
      accompanied by increased cholesterol efflux and apoE secretion in astrocytic
      cultures. We also show that intracerebral delivery of an ASO targeting miR-33
      leads to increased ABCA1 expression in cerebral cortex or subcortical structures
      such as hippocampus. These findings highlight an effective strategy for
      increasing brain ABCA1 expression/activity for relevant mechanistic studies.
      [Corrected]

PMID- 25957560
TI  - Deletion of aquaporin-4 is neuroprotective during the acute stage of micro
      traumatic brain injury in mice.
AB  - Micro traumatic brain injury (TBI) is the most common type of brain injury, but
      the mechanisms underlying it are poorly understood. Aquaporin-4 (AQP4) is a water
      channel expressed in astrocyte end-feet, which plays an important role in brain
      edema. However, little is known about the role of AQP4 in micro TBI. Here, we
      examined the role of AQP4 in the pathogenesis of micro TBI in a closed-skull
      brain injury model, using two-photon microscopy. Our results indicate that AQP4
      deletion reduced cell death, water content, astrocyte swelling and lesion volume
      during the acute stage of micro TBI. Our data revealed that astrocyte swelling is
      a decisive pathophysiological factor in the acute phase of this form of micro
      brain injury. Thus, treatments that inhibit AQP4 could be used as a
      neuroprotective strategy for micro TBI. 

PMID- 25957563
TI  - Research advances in expansins and expansion-like proteins involved in
      lignocellulose degradation.
AB  - Biofuel derived from lignocellulosic biomass has attracted considerable attention
      as a renewable energy source. Nevertheless, the conversion of lignocellulose into
      fermentable sugars is inherently difficult because of the complex structures of
      lignocelluloses. Accessory proteins, like expansins, have a non-hydrolytic
      disruptive effect on crystalline cellulose and can synergistically cooperate with
      cellulase to improve hydrolysis efficiency. This review summarizes recent studies
      on expansins and expansin-like proteins, in terms of their expression and
      purification, synergism in lignocellulose hydrolysis, structure-function studies
      and binding characteristics. Future research prospects are also presented. This
      review provides a discussion of expansins in the context of lignocellulose
      hydrolysis. 

PMID- 25957567
TI  - Regulation of white adipogenesis and its relation to ectopic fat accumulation and
      cardiovascular risk.
AB  - The subcutaneous adipose tissue (SAT) is the largest and least harmful adipose
      depot to store excess lipids. However, SAT has a limited ability to expand and
      recruit new cells. When the SAT adipose cells become expanded (hypertrophic
      obesity), this leads to a dysregulated and dysfunctional SAT and the accumulation
      of ectopic fat in many depots. Increased hepatic and visceral fat are well-known
      ectopic fat depots and reflect the inability of SAT to accommodate excess fat.
      Ectopic fat also leads to paracrine and endocrine effects and promotes the
      metabolic profile of the Metabolic Syndrome. In addition, ectopic fat
      accumulation in and around the heart and vessels are considered to be active and
      cross talk with the tissues, thereby enhancing several aspects associated with
      the risk of developing cardiovascular disease and atherosclerosis. 

PMID- 25957564
TI  - Improvement of 1,3-propanediol production in Klebsiella pneumoniae by moderate
      expression of puuC (encoding an aldehyde dehydrogenase).
AB  - OBJECTIVE: To improve 1,3-propanediol production in Klebsiella pneumoniae, the
      effects of puuC expression in lactate- and lactate/2,3-butanediol-deficient
      strains were assessed. RESULTS: Overexpression of puuC (encoding an aldehyde
      dehydrogenase) inhibited 1,3-propanediol production and increased 3
      hydroxypropionic acid formation in both lactate- and lactate/2,3-butanediol
      deficient strains. An improvement in 1,3-propanediol production was only achieved
      in a lactate-deficient strain via moderate expression of puuC; at the end of the
      fermentation, 1,3-propanediol productivity increased by 14% compared with the
      control. Further comparative analysis of the metabolic flux distributions in
      different strains indicated that 3-hydroxypropionic acid formation could play a
      considerable role in cell metabolism in K. pneumoniae. CONCLUSION: An improvement
      in 3-hydroxypropionic acid formation would be beneficial for cell metabolism,
      which can be accomplished by enhancing 1,3-propanediol productivity in a lactate
      deficient strain via moderate expression of puuC.

PMID- 25957570
TI  - Changes in levels of biomarkers of exposure and biological effect in a controlled
      study of smokers switched from conventional cigarettes to reduced-toxicant
      prototype cigarettes.
AB  - BACKGROUND: Development of cigarettes that reduce exposure to harmful smoke
      constituents is a suggested tobacco harm reduction strategy, but robust methods
      for measurement of change are required. We investigated whether changes in
      biomarkers of exposure (BoE), effective dose (BoED) and biological effect (BoBE)
      could be detected after switching from conventional cigarettes to a reduced
      toxicant-prototype cigarette (RTP). METHODS: Regular smokers of 6-8mg ISO tar
      yield cigarettes were recruited in Hamburg, Germany, and supplied with a
      conventional 7mg ISO tar yield cigarette for 2weeks then switched to the same
      cigarette with a different tipping paper (control) or the RTP for 6months.
      Subjects smoked mostly at home and attended five residential clinic visits where
      urine and blood samples were collected for analysis. Primary endpoints were
      changes in specific biomarker levels compared with non-smoker background levels.
      Changes in daily cigarette consumption were also investigated. RESULTS: BoE
      levels in controls generally increased over the study period, whereas most BoE
      and all BoED significantly declined in RTP smokers. Most BoBE data were similar
      across groups and/or too variable within individuals to detect changes. Increased
      daily cigarette consumption was affected by supply of free cigarettes, perceived
      shorter smoking time per cigarette than usual brands, and perceived reduced harm.
      CONCLUSIONS: Despite increased cigarette consumption, reductions in BoE and BoED
      were detectable.

PMID- 25957572
TI  - Synthesis of novel poly-hydroxyl functionalized acridine derivatives as
      inhibitors of alpha-Glucosidase and alpha-Amylase.
AB  - In this study a novel series of poly-hydroxyl functionalized acridine derivatives
      (L1-L9) was synthesized and their inhibitory activities against alpha-Glucosidase
      (alpha-Gls) and alpha-Amylase (alpha-Amy) were evaluated, spectroscopically. The
      synthetic compounds consist of three different substructures, including a 4-(4
      aminophenoxy) phenyl group (R3), an acridine moiety (R2) and a poly-hydroxy chain
      (R1). The results indicate that among the synthetic compounds, L5 with a
      chromeno[3',4':5,6]pyrido[2,3-d]pyrimidine moiety demonstrates the highest
      inhibitory activity against both yeast and rat alpha-Gls enzymes. Also, L2 with
      the thioxo-pyrido[2,3-d:6,5-d'] dipyrimidine moiety plays an important role in
      the inhibition of yeast alpha-Gls. In addition, the results may suggest a
      significant role for the nature of sugar moiety of the synthetic compounds in
      their inhibitory action against alpha-Gls. Moreover, in comparison with Acarbose,
      which is a widely used anti-diabetic drug, these compounds show negligible
      inhibitory activity against pancreatic alpha-Amy, which is important in the term
      of their reduced susceptibility for possible development of the intestinal
      disturbance side effects. Results of this study may suggest these synthetic
      compounds as novel molecular templates for construction of potentially anti
      diabetic drugs with the ability for more convenient management of postprandial
      hyperglycemia. 

PMID- 25957571
TI  - Regulatory action and moderate decrease in methylphenidate use among ADHD
      diagnosed patients aged five and under in Korea.
AB  - In December 2009, Korean regulatory agency announced that methylphenidate, a drug
      used to treat attention deficit-hyperactivity disorder (ADHD), should not be used
      in children aged five and under due to the risk of sudden cardiac death. This
      study examined the impact of regulatory action and prescribing patterns. We
      conducted a time series analysis using the Korea National Health Insurance
      Service database. Study subjects included children under 18years old with ADHD
      from January 2007 to December 2011. Contraindicated use of methylphenidate was
      defined as use of methylphenidate at least once in children aged five and under.
      We selected additional control points (2007, 2008, and 2010) and compared the
      methylphenidate use one year before and after each point. We calculated relative
      and absolute reductions, and 95% confidence intervals. The total number of ADHD
      patients was 376,298. Overall, there was a 70.87% relative reduction (95% CI:
      63.33%-79.31%) and a 0.93% absolute reduction (95% CI: 0.51%-0.60%) of
      methylphenidate use. The relative and absolute reductions were 27.61% (95% CI:
      24.76%-30.78%) and 0.31% (95% CI: 0.21%-0.41%) in 2007; 43.58% (95% CI: 38.02%
      49.96%) and 0.35% (95% CI: 0.27%-0.43%) in 2008; 46.52% (95% CI: 38.86%-55.70%)
      and 0.21 (95% CI: 0.15%-0.27%) in 2009; and 10.20% (95% CI: 8.32%-12.50%) and
      0.02% (95% CI: 0.02%-0.07%) in 2010. Korean regulatory action led to a moderate
      decrease in contraindicated methylphenidate use even after the steep decline
      before the regulatory action. 

PMID- 25957565
TI  - Multi-dimensional glycan microarrays with glyco-macroligands.
AB  - Glycan microarray has become a powerful high-throughput tool for examining
      binding interactions of carbohydrates with the carbohydrate binding biomolecules
      like proteins, enzymes, antibodies etc. It has shown great potential for
      biomedical research and applications, such as antibody detection and profiling,
      vaccine development, biomarker discovery, and drug screening. Most glycan
      microarrays were made with monovalent glycans immobilized directly onto the array
      surface via either covalent or non-covalent bond, which afford a multivalent
      glycans in two dimensional (2D) displaying. A variety of glyco-macroligands have
      been developed to mimic multivalent carbohydrate-protein interactions for
      studying carbohydrate-protein interactions and biomedical research and
      applications. Recently, a number of glyco-macroligands have been explored for
      glycan microarray fabrication, in particular to mimick the three dimensional (3D)
      multivalent display of cell surface carbohydrates. This review highlights these
      recent developments of glyco-macroligand-based microarrays, predominantly, novel
      glycan microarrays with glyco-macroligands like glycodendrimers, glycopolymers,
      glycoliposomes, neoglycoproteins, and glyconanoparticles with the effort in
      controlling the density and orientation of glycans on the array surface, which
      facilitate both their binding specificity and affinity and thus the high
      performance of glycan microarrays.

PMID- 25957573
TI  - Association of SSR markers with functional traits from heat stress in diverse
      tall fescue accessions.
AB  - BACKGROUND: Heat stress is a critical threat to tall fescue in transitional and
      warm climate zones. Identification of association between molecular markers and
      heat tolerance-related functional traits would promote the efficient selection of
      heat tolerant tall fescue cultivars. Association analysis of heat tolerance
      related traits was conducted in 100 diverse tall fescue accessions consisting of
      93 natural genotypes originating from 33 countries and 7 turf-type commercial
      cultivars. RESULTS: The panel displayed significant genetic variations in growth
      rate (GR), turfgrass quality (TQ), survival rate (SR), chlorophyll content (CHL)
      and evapotranspiration rate (ET) in greenhouse and growth chamber trials. Two
      subpopulations were detected in the panel of accessions by 1010 SSR alleles with
      90 SSR markers, but no obvious relative kinship was observed. 97 and 67 marker
      alleles associated with heat tolerance-related traits were identified in
      greenhouse trial and growth chamber trial (P < 0.01) using mix linear model,
      respectively. Due to different experimental conditions of the two trials, 2 SSR
      marker alleles associated with GR and ET were simultaneously identified at P <
      0.01 level in two trials in response to heat stress. CONCLUSION: High-temperature
      induced great variations of functional traits in tall fescue accessions. And the
      identified marker alleles associated with functional traits could provide
      important information about heat tolerance genetic pathways, and be used for
      molecular assisted breeding to enhance tall fescue performance under heat stress.

PMID- 25957574
TI  - Randomized controlled trial on drowning prevention for parents with children aged
      below five years in Bangladesh: a study protocol.
AB  - BACKGROUND: Drowning is the third leading cause of death for children aged 0-4
      years in many Asian countries, and is a serious but neglected health problem in
      low and middle-income countries like Bangladesh. The aim of the study is to
      outline the study protocol of a trial to test the efficacy of a mobile coach
      based intervention for the prevention of childhood drowning. METHOD/DESIGN: A two
      arm cluster randomized community trial will be conducted to test the efficacy of
      the mobile coach intervention for childhood drowning on parents with children
      below five years of age and compared to an assessment only control group. A total
      of 1680 parents in the villages with children aged below five years of age will
      participate. The village will be used as a randomized unit, randomly assigned to
      an intervention group (N = 840) receiving the mobile coach based intervention or
      an assessment only control group (N = 840). An individualized mobile coach
      intervention based on the demographic data and the individual will be developed,
      and SMSs, audio messages, videos and images about childhood drowning will be sent
      to the participants of the intervention group over a period of six months. The
      participants will receive per week one text message (SMS) and image and one video
      and audio text per month. The primary outcome measure will be increased knowledge
      and safety awareness, and behaviour practice about childhood drowning assessed at
      the six-month follow-up, and the secondary outcome measure will be the reduced
      incidence of childhood drowning in Bangladesh. The study assistants conducting
      the baseline and the follow-up assessments will be blinded regarding the group
      assignment. DISCUSSION: This is the first study testing a fully mobile coach
      intervention for childhood drowning prevention in Bangladesh. It is hoped that
      the programme will offer an effective and inexpensive way to prevent childhood
      drowning among children aged below five years and also increase the awareness of
      parents concerning the risks to their children from drowning. TRIAL REGISTRATION:
      ISRCTN13774693, 08/03/2015.

PMID- 25957569
TI  - Interfacial reaction of Sn(II) on mackinawite (FeS).
AB  - The interaction of Sn(II) with metastable, highly reactive mackinawite is a
      complex process due to transient changes of the mackinawite surface in the
      sorption process. In this work, we show that tin redox state and local structure
      as investigated by Sn-K X-ray absorption spectroscopy (XAS) change with pH. We
      observe at pH<7 that divalent Sn forms two short (2.38 A) Sn-S bonds to the S
      terminated surface of mackinawite, and two longer (2.59 A) Sn-S bonds pointing
      most likely towards the solution phase, in line with a SnS4 innersphere sorption
      complex. Precipitation of SnS or formation of a solid solution with mackinawite
      could be excluded. At pH>9, Sn(II) is completely oxidized to Sn(IV) by an
      Fe(II)/Fe(III) (hydr)oxide, most likely green rust, forming on the surface of
      mackinawite. Six O atoms at 2.04 A and 6 Fe atoms at 3.29 A indicate a structural
      incorporation by green rust, with Sn(IV) substituting for Fe in the crystal
      structure. The transition between Sn(II) and Sn(IV) and between sulfur and oxygen
      coordination takes place at a pH of 7 to 8 and an Eh of -250 mV, close to the
      thermodynamically predicted transitions from mackinawite to Fe (hydr)oxide and
      from sulfide to sulfate. The uptake processes of Sn(II) by mackinawite are
      largely in line with the uptake processes of divalent cations with soft Lewis
      acid character like Cd, Hg and Pb, and lead to a strong retention of Sn with
      logRd values from 5 to 7 across the investigated pH range of 5 to 11.

PMID- 25957566
TI  - Cellular metabolism of unnatural sialic acid precursors.
AB  - Carbohydrates, in addition to their metabolic functions, serve important roles as
      receptors, ligands, and structural molecules for diverse biological processes.
      Insight into carbohydrate biology and mechanisms has been aided by metabolic
      oligosaccharide engineering (MOE). In MOE, unnatural carbohydrate analogs with
      novel functional groups are incorporated into cellular glycoconjugates and used
      to probe biological systems. While MOE has expanded knowledge of carbohydrate
      biology, limited metabolism of unnatural carbohydrate analogs restricts its use.
      Here we assess metabolism of SiaDAz, a diazirine-modified analog of sialic acid,
      and its cell-permeable precursor, Ac4ManNDAz. We show that the efficiency of
      Ac4ManNDAz and SiaDAz metabolism depends on cell type. Our results indicate that
      different cell lines can have different metabolic roadblocks in the synthesis of
      cell surface SiaDAz. These findings point to roles for promiscuous intracellular
      esterases, kinases, and phosphatases during unnatural sugar metabolism and
      provide guidance for ways to improve MOE.

PMID- 25957577
TI  - Efficacy of virtual reality-based intervention on balance and mobility disorders
      post-stroke: a scoping review.
AB  - Rehabilitation interventions involving virtual reality (VR) technology have been
      developed for the promotion of functional independence post stroke. A scoping
      review was performed to examine the efficacy of VR-based interventions on balance
      and mobility disorders post stroke. Twenty-four articles in the English language
      examining VR game-based interventions and outcomes directed at balance and
      mobility disorders were included. Various VR systems (customized and commercially
      available) were used as rehabilitation tools. Outcome measures included
      laboratory and clinical measures of balance and gait. Outcome measures of dynamic
      balance showed significant improvements following VR-based interventions as
      compared to other interventions. Further, it was observed that VR-based
      intervention may have favorable effects in improving walking speed and the
      ability to deal with environmental challenges, which may also facilitate
      independent community ambulation. VR-based therapy thus has the potential to be a
      useful tool for balance and gait training for stroke rehabilitation. Utilization
      of motor learning principles related to task-related training may have been an
      important factor leading to positive results. Other principles such as
      repetition, feedback etc. were used in studies but were not explored explicitly
      and may need to be investigated to further improve the strength of results.
      Lastly, robust study designs with appropriate attention towards the intensity and
      dose-response aspects of VR training, clear study objectives and suitable
      outcomes would further aid in determining evidence-based efficacy for VR game
      based interventions in the future. 

PMID- 25957568
TI  - Subclinical atherosclerosis and subsequent cognitive function.
AB  - OBJECTIVE: To examine the relationship between measures of subclinical
      atherosclerosis and subsequent cognitive function. METHOD: Participants from the
      Dallas Heart Study (DHS), a population-based multiethnic study of cardiovascular
      disease pathogenesis, were re-examined 8 years later (DHS-2) with the Montreal
      Cognitive Assessment (MoCA); N = 1904, mean age = 42.9, range 8-65. Associations
      of baseline measures of subclinical atherosclerosis (coronary artery calcium,
      abdominal aortic plaque, and abdominal aortic wall thickness) with MoCA scores
      measured at follow-up were examined in the group as a whole and in relation to
      age and ApoE4 status. RESULTS: A significant linear trend of successively lower
      MoCA scores with increasing numbers of atherosclerotic indicators was observed
      (F(3, 1150) = 5.918, p = .001). CAC was weakly correlated with MoCA scores (p =
      .047) and MoCA scores were significantly different between participants with and
      without CAC (M = 22.35 vs 23.69, p = 0.038). With the exception of a small
      association between abdominal AWT and MoCA in subjects over age 50, abdominal AWT
      and abdominal aortic plaque did not correlate with MoCA total score (p >= .052).
      Cognitive scores and atherosclerosis measures were not impacted by ApoE4 status
      (p >= .455). CONCLUSION: In this ethnically diverse population-based sample,
      subclinical atherosclerosis was minimally associated with later cognitive
      function in middle-aged adults.

PMID- 25957575
TI  - Diffuse leptomeningeal gliomatosis initially presenting with intraventricular
      hemorrhage: a case report and literature review.
AB  - BACKGROUND: Primary diffuse leptomeningeal gliomatosis (PDLG) is a lethal
      neoplasm that is characterized by glioma cells exclusively infiltrating into
      cerebral and spinal meninges. Intraventricular hemorrhage as an initial symptom
      in PDLG patient has not been reported in the literatures. CASE PRESENTATION: A 39
      year-old man initially presented with intraventricular hemorrhage. The patient
      had an improved outcome at the early stage of hemorrhagic course; however, the
      clinical condition began to a sudden turn for deterioration with intracranial
      hypertension and cerebral hernia on day 15 after admission. Cerebral CT and MRI
      showed diffuse patchy signals with enhancement in bilateral cerebellopontine
      angle cistern, suprasellar cistern, ambient cistern, quadrigeminal cistern,
      bilateral cerebellum, cerebral hemisphere, and upper cervical cord surface.
      Pathological examination revealed that numerous spindled cells were scant of
      cytoplasm with hyperchromatic nuclei and various mitotic figures.
      Immunohistochemistry showed that the cells were positive to glial fibrillary
      acidic protein (GFAP) with about 5% Ki-67 positive labeling. The pathological
      findings were consistent with the diagnostic criteria of anaplastic astrocytoma
      (WHO grade III). CONCLUSION: We reported an interesting case that PDLG initially
      presented with intraventricular hemorrhage that might be caused by astrocytoma
      rupturing into pial vessels.

PMID- 25957578
TI  - Hospital discharges for fever and neutropenia in pediatric cancer patients:
      United States, 2009.
AB  - BACKGROUND: Fever and neutropenia (FN) is a common complication of pediatric
      cancer treatment, but hospital utilization patterns for this condition are not
      well described. METHODS: Data were analyzed from the Kids' Inpatient Database
      (KID), an all-payer US hospital database, for 2009. Pediatric FN patients were
      identified using: age <=19 years, urgent or emergent admit type, non-transferred,
      and a combination of ICD-9-CM codes for fever and neutropenia. Sampling weights
      were used to permit national inferences. RESULTS: Pediatric cancer patients
      accounted for 1.5 % of pediatric hospital discharges in 2009 (n = 110,967), with
      10.1 % of cancer-related discharges meeting FN criteria (n = 11,261). Two-fifths
      of FN discharges had a "short length of stay" (SLOS) of <=3 days, which accounted
      for approximately $65.5 million in hospital charges. Upper respiratory infection
      (6.0 %) and acute otitis media (AOM) (3.7 %) were the most common infections
      associated with SLOS. Factors significantly associated with SLOS included living
      in the Midwest region (OR = 1.65, 1.22-2.24) or West region (OR 1.54, 1.11-2.14)
      versus Northeast, having a diagnosis of AOM (OR = 1.39, 1.03-1.87) or viral
      infection (OR = 1.63, 1.18-2.25) versus those without those comorbidities, and
      having a soft tissue sarcoma (OR = 1.47, 1.05-2.04), Hodgkin lymphoma (OR = 2.33,
      1.62-3.35), or an ovarian/testicular tumor (OR = 1.76, 1.05-2.95) compared with
      patients without these diagnoses. CONCLUSION: FN represents a common precipitant
      for hospitalizations among pediatric cancer patients. SLOS admissions are rarely
      associated with serious infections, but contribute substantially to the burden of
      hospitalization for pediatric FN.

PMID- 25957579
TI  - Predictors of Ominous Outcome in Infants who Undergo Cardiac Surgery and
      Cardiopulmonary By-Pass: S100B Protein.
AB  - S100B protein has been recently proposed as a consolidated marker of brain damage
      and death in adult, children and newborn patients. The present study evaluates
      whether the longitudinal measurement of S100B at different perioperative time
      points may be a useful tool to identify the occurrence of perioperative early
      death in congenital heart disease (CHD) newborns. We conducted a case-control
      study in 88 CHD infants, without pre-existing neurological disorders or other co
      morbidities, of whom 22 were complicated by perioperative death in the first week
      from surgery. Control group was composed by 66 uncomplicated CHD infants matched
      for age at surgical procedure. Blood samples were drawn at five predetermined
      timepoints before during and after surgery. In all CHD children, S100B levels
      showed a pattern characterized by a significant increase in protein's
      concentration from hospital admission up to 24-h after procedure reaching their
      maximum peak (P<0.01) during cardiopulmonary by-pass and at the end of the
      surgical procedure. Moreover, S100B concentrations in CHD death group were
      significantly higher (P<0.01) than controls at all monitoring time-points. The
      ROC curve analysis showed that S100B measured before surgical procedure was the
      best predictor of perioperative death, among a series of clinical and laboratory
      parameters, reaching at a cut-off of 0.1 ug/L a sensitivity of 100% and a
      specificity of 63.7%. The present data suggest that in CHD infants biochemical
      monitoring in the perioperative period is becoming possible and S100B can be
      included among a series of parameters for adverse outcome prediction. 

PMID- 25957576
TI  - Identification of phlebotomine sand flies using one MALDI-TOF MS reference
      database and two mass spectrometer systems.
AB  - BACKGROUND: Rapid, accurate and high-throughput identification of vector
      arthropods is of paramount importance in surveillance programmes that are
      becoming more common due to the changing geographic occurrence and extent of many
      arthropod-borne diseases. Protein profiling by MALDI-TOF mass spectrometry
      fulfils these requirements for identification, and reference databases have
      recently been established for several vector taxa, mostly with specimens from
      laboratory colonies. METHODS: We established and validated a reference database
      containing 20 phlebotomine sand fly (Diptera: Psychodidae, Phlebotominae) species
      by using specimens from colonies or field-collections that had been stored for
      various periods of time. RESULTS: Identical biomarker mass patterns
      ('superspectra') were obtained with colony- or field-derived specimens of the
      same species. In the validation study, high quality spectra (i.e. more than 30
      evaluable masses) were obtained with all fresh insects from colonies, and with
      55/59 insects deep-frozen (liquid nitrogen/-80  degrees C) for up to 25 years. In
      contrast, only 36/52 specimens stored in ethanol could be identified. This
      resulted in an overall sensitivity of 87 % (140/161); specificity was 100 %.
      Duration of storage impaired data counts in the high mass range, and thus cluster
      analyses of closely related specimens might reflect their storage conditions
      rather than phenotypic distinctness. A major drawback of MALDI-TOF MS is the
      restricted availability of in-house databases and the fact that mass
      spectrometers from 2 companies (Bruker, Shimadzu) are widely being used. We have
      analysed fingerprints of phlebotomine sand flies obtained by automatic routine
      procedure on a Bruker instrument by using our database and the software
      established on a Shimadzu system. The sensitivity with 312 specimens from 8 sand
      fly species from laboratory colonies when evaluating only high quality spectra
      was 98.3 %; the specificity was 100 %. The corresponding diagnostic values with
      55 field-collected specimens from 4 species were 94.7 % and 97.4 %, respectively.
      CONCLUSIONS: A centralized high-quality database (created by expert taxonomists
      and experienced users of mass spectrometers) that is easily amenable to customer
      oriented identification services is a highly desirable resource. As shown in the
      present work, spectra obtained from different specimens with different
      instruments can be analysed using a centralized database, which should be
      available in the near future via an online platform in a cost-efficient manner.

PMID- 25957580
TI  - Identification of an anti-TB compound targeting the tyrosyl-tRNA synthetase.
AB  - OBJECTIVES: Drug-resistant Mycobacterium tuberculosis poses a great threat to
      human health. Tyrosyl-tRNA synthetase (TyrRS) is one of the aminoacyl tRNA
      synthetases that catalyse the attachment of amino acids to their cognate tRNAs
      and are essential for protein synthesis. There are several distinctive
      differences between bacterial and human TyrRS and therefore it could be a
      potential target for developing antimicrobial agents. This study aimed to
      identify a new anti-TB agent targeting M. tuberculosis TyrRS (MtTyrRS). METHODS:
      We first used Mycobacterium smegmatis for a phenotypic screening of 20 000
      compounds. The hit compounds were then screened with MtTyrRS. The interaction
      between hit compound IMB-T130 and the target protein was analysed by surface
      plasmon resonance (SPR) assay and molecular docking experiments. The target of
      IMB-T130 was further confirmed by the overexpression of the target protein. The
      antibacterial activity of IMB-T130 against various standard and clinical drug
      resistant M. tuberculosis strains was evaluated using the microplate Alamar blue
      assay. RESULTS: Compound IMB-T130 was identified as a hit compound that inhibits
      the growth of M. smegmatis and the in vitro activity of MtTyrRS. The interaction
      between IMB-T130 and MtTyrRS was confirmed by SPR assay and molecular docking
      analysis. The higher MIC for a strain overexpressing the target protein also
      suggests that MtTyrRS is likely to be the target of IMB-T130. IMB-T130 shows
      excellent anti-TB activity and low cytotoxicity. CONCLUSIONS: IMB-T130 inhibits
      the growth of MDR-TB and XDR-TB by targeting MtTyrRS. Because of its low
      cytotoxicity against mammalian cells, IMB-T130 is a promising new agent against
      drug-resistant M. tuberculosis.

PMID- 25957581
TI  - Emergence and spread of O16-ST131 and O25b-ST131 clones among faecal CTX-M
      producing Escherichia coli in healthy individuals in Hunan Province, China.
AB  - OBJECTIVES: The objectives of this study were to determine CTX-M-producing
      Escherichia coli ST131 strain prevalence in stool specimens from healthy subjects
      in central China and to molecularly characterize clonal groups. METHODS: From
      November 2013 to January 2014, stool specimens from healthy individuals in Hunan
      Province were screened for ESBL-producing E. coli using chromogenic medium and
      CTX-M genotypes and phylogenetic groups were determined. ST131 clonal groups were
      detected by PCR and characterized for antibiotic resistance, fimH, gyrA and parC
      alleles, plasmid-mediated quinolone resistance determinants, virulence genotypes
      and PFGE patterns. RESULTS: Among 563 subjects, 287 (51.0%) exhibited the
      presence of faecal ESBL-producing E. coli, all of which produced CTX-M enzymes.
      The most common CTX-M genotypes were CTX-M-14 (48.4%), CTX-M-15 (27.5%) and CTX-M
      27 (15.0%). Of the 287 CTX-M-producing isolates, 32 (11.1%) belonged to the ST131
      clone. O16-ST131 isolates were dominant (75%) and contained the fimH41 allele.
      The remaining eight (25%) ST131 isolates were of the O25b subgroup and contained
      fimH30 or fimH41. Ciprofloxacin resistance was found in 100% of the O25b-ST131
      isolates, whereas only 8% of the O16-ST131 isolates were resistant. All of the
      O25b-ST131 isolates except one showed gyrA1AB and parC1aAB mutations; most of the
      O16-ST131 isolates had gyrA1A and parC1b mutations. The virulence genotypes of
      O16-ST131 resembled those of the O25b-ST131 isolates. The 32 ST131 isolates
      formed one large group at the 64% similarity level. They comprised 15 PFGE groups
      (defined at >=85% similarity). CONCLUSIONS: O16-ST131 isolates have emerged as
      the predominant type of ST131 isolate in faecal CTX-M-producing E. coli in
      healthy individuals in China.

PMID- 25957582
TI  - Central Nervous System and Peripheral Expression of CCL19, CCL21 and Their
      Receptor CCR7 in Experimental Model of Multiple Sclerosis.
AB  - It is well documented that inflammatory chemokines play a significant role in the
      development of multiple sclerosis (MS) and its model, experimental autoimmune
      encephalomyelitis (EAE). Recently, the involvement of homeostatic (or lymphoid)
      chemokines in the pathogenesis of autoimmune diseases has become an object of
      intensive study. In this work, quantitative analysis of CCL19, CCL21 and CCR7
      expression in the central nervous system (CNS), as well as in inflammatory
      mononuclear cells isolated from several organs during the first attack, remission
      and the second attack of chronic-relapsing EAE (ChREAE), was performed. Using
      real-time PCR, RNAse Protection Assay and immunohistochemistry, the expression of
      both chemokines, as well as of their common receptor CCR7, was analyzed in the
      brain, spleen, lymph nodes and peripheral blood mononuclear cells. Increased
      expression of CCL19 and CCL21 was observed mostly in mononuclear inflammatory
      cells isolated from the CNS during active ChREAE. At the same time the expression
      of CCR7 in blood mononuclear leukocytes was reduced. This observation extends our
      current knowledge about the possible role of chemokines CCL19, CCL21 and their
      receptor CCR7 in the pathogenesis of ChREAE and, by extension, MS. 

PMID- 25957583
TI  - Transdifferentiation of Bone Marrow Mesenchymal Stem Cells into the Islet-Like
      Cells: the Role of Extracellular Matrix Proteins.
AB  - Pancreatic islet implantation has been recently shown to be an efficient method
      of treatment for type 1 diabetes. However, limited availability of donor islets
      reduces its use. Bone morrow would provide potentially unlimited source of stem
      cells for generation of insulin-producing cells. This study was performed to
      evaluate the influence of extracellular matrix proteins like collagen, laminin,
      and vitronectin on bone marrow mesenchymal stem cells (BM-MSCs)
      transdifferentiation into islet-like cells (ILCs) in vitro. To our knowledge,
      this is the first report evaluating the importance of vitronectin in
      transdifferentiation of BM-MSCs into ILCs. Rat BM-MSCs were induced to ILCs using
      four-step protocol on plates coated with collagen type IV, laminin type I and
      vitronectin type I. Quantitative real-time PCR was performed to detect gene
      expression related to pancreatic beta cell development. The induced cells
      expressed islet-related genes including: neurogenin 3, neurogenic differentiation
      1, paired box 4, NK homeobox factor 6.1, glucagon, insulin 1 and insulin 2.
      Laminin but not collagen type IV or vitronectin enhanced expression of insulin
      and promoted formation of islet-like structures in monolayer culture. Laminin
      triggered transdifferentiation of BM-MSCs into ILCs. 

PMID- 25957586
TI  - ARL6IP6, a susceptibility locus for ischemic stroke, is mutated in a patient with
      syndromic Cutis Marmorata Telangiectatica Congenita.
AB  - Cutis Marmorata Telangiectatica Congenita (CMTC) is a congenital localized or
      generalized vascular anomaly, usually sporadic in occurrence. It can be
      associated with other cutaneous or systemic manifestations. About 300 cases have
      been reported. The molecular etiology remains largely unknown. The main purpose
      of this study is to delineate the molecular basis for a syndromic CMTC phenotype
      in a consanguineous Saudi family. Clinical phenotyping including detailed
      neurological imaging, followed by autozygosity mapping and trio whole exome
      sequencing (WES) are also studied. We have identified a homozygous truncating
      mutation in ARL6IP6 as the likely cause of a syndromic form of CMTC associated
      with major dysmorphism, developmental delay, transient ischemic attacks and
      cerebral vascular malformations. This gene was previously implicated by genome
      wide association study (GWAS) as a susceptibility locus to ischemic stroke in
      young adults. We identify ARL6IP6 as a novel candidate gene for a syndromic form
      of CMTC. This suggests that ischemic stroke or transient ischemic attacks (TIA)
      may represent, at least in some cases, the mild end of a phenotypic spectrum that
      has at its severe end autosomal recessive CMTC. This finding contributes to a
      growing appreciation of the continuum of Mendelian and common complex diseases. 

PMID- 25957584
TI  - The role of purinergic signaling in the etiology of migraine and novel
      antimigraine treatment.
AB  - Etiopathogenesis of migraine involves different structures of the central nervous
      system: the trigeminal nerve with nuclei located in the brain stem, vascular
      system, and the cerebral cortex as well as diverse mechanisms and pathological
      processes. The multidirectional action of purines in different cell types (blood
      vessels, neurons, and satellite glial cells) and through different types of
      purinergic receptors contributes to the etiopathogenesis of migraine pain.
      Adenosine triphosphate (ATP) and its derivatives are involved in initiation and
      propagation of migrenogenic signals in several ways: they participate in
      vasomotor mechanism, cortical spreading depression, and in fast transmission or
      cross-excitation based on the satellite glial cells in trigeminal ganglion.
      Contribution of purinergic signaling in the conduction of pain is realized
      through the activation of P1 and P2 receptors expressed widely in the central
      nervous system: on the neurons and glial cells as well as on the smooth muscles
      and endothelium in the vascular system. Therefore, the purinergic receptors can
      be an excellent target for pharmacologists constructing new antimigraine
      therapeutics. Moreover, the mechanisms facilitating ATP and adenosine degradation
      may prevent vasodilatation and thus avoid a secondary central sensitization
      during a migraine attack. Thus, agonists and antagonists of P receptors as well
      as ecto-enzymes metabolizing nucleotides/nucleosides could gain the growing
      attention as therapeutic agents. 

PMID- 25957585
TI  - Cytochrome c oxidase deficit is associated with the seizure onset zone in young
      patients with focal cortical dysplasia Type II.
AB  - It has been postulated that mitochondrial dysfunction may be an important factor
      in epileptogenesis of intractable epilepsy. The current study tests the
      hypothesis that mitochondrial Complex IV (CIV) or cytochrome c oxidase
      dysfunction is associated with the seizure onset zone (SOZ) in patients with
      focal cortical dysplasia (FCD). Subjects were selected based on: age <19y;
      epilepsy surgery between May, 2010 and October, 2011; pathological diagnosis of
      isolated focal cortical dysplasia Type I (FCDI) or Type II (FCDII); and
      sufficient residual cortical tissue to conduct analysis of electron transport
      chain complex (ETC) activity in SOZ and adjacent cortical regions. In this
      retrospective study, patients were identified who had sufficient unfixed, frozen
      brain tissue for biochemical analysis in tissue homogenates. Specimens were
      subtyped using ILAE classification for FCD, and excluded if diagnosed with FCD
      Type III or dual pathology. Analysis of ETC activity in resected tissues was
      conducted independently and without knowledge of the identity, diagnosis, or
      clinical status of individual subjects. Seventeen patients met the inclusion
      criteria, including 6 FCDI and 11 FCDII. Comparison of adjacent cortical
      resections showed decreased CIV activity in the SOZ of the FCDII group (P =
      0.003), but no significant CIV difference in adjacent tissues of the FCDI group.
      Because of the importance of CIV as the terminal and rate-limiting complex in the
      mitochondrial electron transport chain, these authors conclude that 1) a deficit
      of CIV is associated with the SOZ of patients with FCDII; 2) CIV deficiency may
      contribute to the spectrum of FCD neuropathology; and 3) further investigation of
      CIV in FCD may lead to the discovery of new targets for neuroprotective therapies
      for patients with intractable epilepsy. 

PMID- 25957587
TI  - Copy number variation in the human Y chromosome in the UK population.
AB  - We have assessed copy number variation (CNV) in the male-specific part of the
      human Y chromosome discovered by array comparative genomic hybridization (array
      CGH) in 411 apparently healthy UK males, and validated the findings using SNP
      genotype intensity data available for 149 of them. After manual curation taking
      account of the complex duplicated structure of Y-chromosomal sequences, we
      discovered 22 curated CNV events considered validated or likely, mean 0.93 (range
      0-4) per individual. 16 of these were novel. Curated CNV events ranged in size
      from <1 kb to >3 Mb, and in frequency from 1/411 to 107/411. Of the 24 protein
      coding genes or gene families tested, nine showed CNV. These included a large
      duplication encompassing the AMELY and TBL1Y genes that probably has no
      phenotypic effect, partial deletions of the TSPY cluster and AZFc region that may
      influence spermatogenesis, and other variants with unknown functional
      implications, including abundant variation in the number of RBMY genes and/or
      pseudogenes, and a novel complex duplication of two segments overlapping the AZFa
      region and including the 3' end of the UTY gene.

PMID- 25957588
TI  - Anthropometric study of the proximal radius: does radial head implant fit in all
      cases?
AB  - PURPOSE: The purpose of this study was to evaluate anthropometry of the radial
      head and neck and compare the results with radial head prosthesis in current use.
      METHODS: A total of 144 cases were analysed that underwent antero-posterior (AP)
      elbow radiographs in full supination and extension position between January 2013
      and April 2013. Mean age was 54.3 years (range, 21-79). The distance between the
      articular surface and the radial tuberosity, the height of the radial head, the
      diameter of the radial head, and the width of the proximal radioulnar joint were
      measured. The specifications of 13 products from nine companies were compared
      with the parameters. RESULTS: The mean distance between the articular surface and
      the radial tuberosity was 19.6 mm. Mean height, diameter, and width of the
      proximal radioulnar joint were 10.6, 22.0, and 8.9 mm, respectively. A violation
      of the distal biceps insertion will occur in up to 87.5 % of the cases when some
      of the bipolar implants were used. The height of some of the implant heads was
      larger than the height of head in our study. Although the height and diameter of
      the radial head were similar to those of previous reports, the distance between
      the articular surface of the head and radial tuberosity was different.
      CONCLUSION: The anatomical parameters of the proximal radius of the cases,
      especially the distance between the articular surface of the head and the radial
      tuberosity, and the radial head implant specifications should be assessed when
      selecting a radial head implant.

PMID- 25957589
TI  - The oblique fracture of the manubrium sterni caused by a seatbelt--a rare injury?
      Treatment options based on the experiences gained in a level I trauma centre.
AB  - INTRODUCTION: Sternal fractures are rare with 3-8 % out of the total number of
      trauma cases mostly caused by direct impact to the anterior chest wall. Most
      cases described are due to motor vehicle crash either caused by direct impact to
      the steering wheel or by the seat belt. Fractures mainly occur to the sternal
      body. Only rarely are cases of manubrium fractures described in literature, for
      example, in relationship with a direct impact to the shoulder which caused an
      oblique fracture near to the sternoclavicular joint. Three patients with
      profoundly dislocated oblique manubrium fracture were admitted to our Level I
      Trauma Center in 2012 and 2013. Those patients suffered from instability of the
      upper sternum and the shoulder girdle. MATERIAL AND METHODS: Between January 2012
      and October 2013, a total of 538 trauma patients were admitted to the emergency
      room and received whole body CT-scan. They were analysed retrospectively for
      sternal fractures. In cases of instability and dislocation, fracture
      stabilisation was performed by anterior plating through a medial approach using
      low profile titanium plates (MatrixRib(r)). RESULTS: Seventy-nine (14.7 %)
      patients showed sternal fracture, out of which 13 (2.4 %) patients showed a
      fracture of manubrium, ten caused by seatbelt. In three cases stabilization was
      performed. Follow up showed sufficient consolidation without complications.
      DISCUSSION: A total of 16.5 % of sternal fractures were localized at the
      manubrium, mostly caused by seat belt. Fractures without significant dislocation
      seemed to be stable and healed well under conservative treatment. Dislocation in
      this region leads to unstable shoulder girdle. Anterior plating provides
      sufficient stabilisation and allowed consolidation.

PMID- 25957590
TI  - Fluoroscopy assessment during anterior minimally invasive hip replacement is more
      accurate than with the posterior approach.
AB  - PURPOSE: Acetabular component position is important for stability and wear.
      Fluoroscopy can improve the accuracy of acetabular component placement in the
      posterior approach and the direct anterior approach (DAA). The purpose of this
      study was to determine if the direct anterior approach in the supine position
      facilitates the accurate use of fluoroscopy and improves acetabular component
      position. METHODS: This retrospective, comparative study of 60 THAs with
      fluoroscopic guidance (30 in posterior approach group and 30 in DAA group) was
      performed by one surgeon from 2012 to 2014 at a single institution. Demographic
      and perioperative data were compared using the Kolmogorov-Smirnov test to
      determine if they were statistically different. The difference between the
      measured intra-operative and postoperative values for both inclination and
      anteversion were analysed respectively. RESULTS: In the posterior approach group
      we found an average inclination on intra-operative fluoroscopy (IFluoro) of 36.8
      degrees  +/- 3.72 degrees , an average anteversion on intra-operative fluoroscopy
      (AFluoro) of 25.6 degrees  +/- 3.64 degrees , an average inclination on
      postoperative standing AP pelvis X-ray (IAP X-ray) of 39.29 degrees  +/- 4.58
      degrees  and an average anteversion on postoperative standing AP pelvis X-ray
      (AAP X-ray) of 21.31 degrees  +/- 4.04 degrees . In the DAA group we found an
      average DAA IFluoro of 42.32 degrees  +/- 1.91 degrees , an average DAA AFluoro
      of 22.3 degrees  +/- 1.41 degrees , an average DAA IAP X-ray of 42.98 degrees  +/
      1.81 degrees  and an average DAA AAP X-ray of 22.88 degrees  +/- 1.38 degrees .
      A difference was seen in variability using Kolmogorov-Smirnov test for
      inclination and anteversion with significant higher variation of measurements in
      the posterior approach group (p = 0.022 and p < 0.001 respectively). No
      statistically significant difference was seen in the DAA group using the
      fluoroscopy for inclination and anteversion. CONCLUSION: Using fluoroscopy in the
      direct anterior approach, we achieved better intra-operative assessment of cup
      orientation resulting in decreased variability of acetabular cup anteversion than
      when used in the posterior approach. At least some of the improvement was due to
      the fact that the fluoroscopic image in the supine position was more accurate as
      measured against the postoperative standing AP pelvis. This study may influence
      the choice of approach in total hip replacement.

PMID- 25957592
TI  - TALL score for prediction of oncological outcomes after radical
      nephroureterectomy for high-grade upper tract urothelial carcinoma.
AB  - PURPOSE: We created a prognostic tool for the prediction of oncologic outcomes
      after radical nephroureterectomy (RNU) for high-grade non-metastatic upper tract
      urothelial carcinoma (UTUC). METHODS: UTUC collaboration was utilized to include
      586 patients who underwent RNU for non-metastatic high-grade UTUC. Survival
      outcomes were compared according to a score defined based on the sum of the
      independent prognostic variables. RESULTS: The study included 382 males with a
      median age 70 years (range 28-97). Independent prognostic factors included: T (t
      stage), A (architecture), LVI (lympho-vascular invasion) and L (lymphadenectomy).
      TALL score (1-7) was the sum of T (<=T1 = 1, T2 = 2, T3 = 3 and T4 = 4), A
      (papillary = 0 and sessile = 1), LVI (absent = 0 and present = 1) and L
      (lymphadenectomy = 0 and no lymphadenectomy = 1). Five-year disease-free survival
      (DFS) and cancer-specific survival (CSS) were stratified into four risk
      categories according to the TALL score: low (TALL 0-2; 86 % DFS and 90 % CSS),
      intermediate (TALL = 3; 71 % DFS and 75 % CSS), high (TALL = 4; 57 % DFS and 58 %
      CSS) and very high risk (TALL >= 5; 34 % DFS and 38 % CSS) using Kaplan-Meier
      survival analyses. TALL score was externally validated in a single-center cohort
      of 85 UTUC patients. CONCLUSIONS: We developed a multivariable prognostic tool
      for the prediction of oncological outcomes after RNU for high-grade UTUC. The
      score can be used for patient counseling, selection for adjuvant systemic
      therapies and design of clinical trials.

PMID- 25957591
TI  - Downstream effects of endocannabinoid on blood cells: implications for health and
      disease.
AB  - Endocannabinoids (eCBs), among which N-arachidonoylethanolamine (AEA) and 2
      arachidonoylglycerol (2-AG) are the most biologically active members, are
      polyunsaturated lipids able to bind cannabinoid, vanilloid and peroxisome
      proliferator-activated receptors. Depending on the target engaged, these
      bioactive mediators can regulate different signalling pathways, at both central
      and peripheral levels. The biological action of eCBs is tightly controlled by a
      plethora of metabolic enzymes which, together with the molecular targets of these
      substances, form the so-called "endocannabinoid system". The ability of eCBs to
      control manifold peripheral functions has received a great deal of attention,
      especially in the light of their widespread distribution in the body. In
      particular, eCBs are important regulators in blood, where they modulate
      haematopoiesis, platelet aggregation and apoptosis, as well as chemokine release
      and migration of immunocompetent cells. Here, we shall review the current
      knowledge on the pathophysiological roles of eCBs in blood. We shall also discuss
      the involvement of eCBs in those disorders affecting the haematological system,
      including cancer and inflammation. Knowledge gained to date underlines a
      fundamental role of the eCB system in blood, thus suggesting that it may
      represent a therapeutic promise for a broad range of diseases involving impaired
      hematopoietic cell functions. 

PMID- 25957593
TI  - T cells, mast cells and microvascular density in diffuse large B cell lymphoma.
AB  - Diffuse large B cell lymphoma (DLBCL) is recognized as the most common form of
      non-Hodgkin lymphoma (NHL), accounting for about 40 % of all cases of NHL. Among
      the cellular components of the tumor inflammatory infiltrate, T cells and mast
      cells have been demonstrated to be correlated with tumor angiogenesis. In this
      report, we have investigated CD3 and tryptase expression and their relationship
      with microvascular density (MVD) in DLBCL patients. Moreover, we determined the
      significance of CD3 expression in bulky and non-bulky disease. CD3 expression was
      significantly lower in bulky disease patients when compared to non-bulky ones.
      CD3 showed a positive correlation with tryptase and MVD, while multiple
      regression analysis efficaciously predicted MVD depending on CD3 and tryptase as
      predictors, supporting a complex interplay between these cells in sustaining
      tumor angiogenesis in DLBCL patients. 

PMID- 25957594
TI  - Comparison of breast cancer risk in women with and without systemic lupus
      erythematosus in a Medicare population.
AB  - Studies have suggested a decreased breast cancer risk in women with systemic
      lupus erythematosus. However, these studies enrolled younger patients identified
      primarily from lupus clinics. We compared the 5-year incidence of breast cancer
      among women with and without a diagnosis of SLE in a large population-based study
      of Medicare beneficiaries. We used a 20 % sample to create a cohort of 3,670,138
      women from 2006 Medicare claims data with and without SLE at baseline. The study
      had 80 % power to detect whether the 5-year breast cancer incidence in the SLE
      cohort was 13 % higher or lower than the non-SLE cohort. Of the 18,423 women with
      SLE, 21 % were African American and 53 % were >=65 years. The absolute age
      adjusted risk for breast cancer in women with SLE was 2.23 (95 % CI 1.94-2.55)
      and 2.14 (95 % CI 1.96-2.34) in controls per 100 women. The overall absolute age
      and race adjusted incidence rate was 1.04 (95 % CI 0.90-1.21). Among women with
      SLE from "Others" (Hispanic, Native American, and/or Asian), the age-adjusted
      risk for breast cancer was 2.44 per 100 women (95 % CI 1.07-2.18), and age
      adjusted incidence rate was 1.52 (95 % CI 1.07-2.18). In contrast to prior clinic
      based studies, this population-based cohort study showed that the risk of breast
      cancer in women with SLE was not lower than in women without SLE. Women with SLE
      should follow routine breast cancer screening recommendations for their age group
      to avoid delay in diagnosis, because the presence of SLE may affect selection of
      early breast cancer therapies.

PMID- 25957595
TI  - Circulating tumor cell clusters-associated gene plakoglobin and breast cancer
      survival.
AB  - Breast cancer recurrence is a major cause of the disease-specific death.
      Circulating tumor cells (CTCs) are negatively associated with breast cancer
      survival. Plakoglobin, a cell adhesion protein, was recently reported as a
      determinant of CTCs types, single or clustered ones. Here, we aim to summarize
      the studies on the roles of plakoglobin and evaluate the association of
      plakoglobin and breast cancer survival. Plakoglobin as a key component in both
      cell adhesion and the signaling pathways was briefly reviewed first. Then the
      double-edge functions of plakoglobin in tumors and its association with CTCs and
      breast cancer metastasis were introduced. Finally, based on an open-access
      database, the association between plakoglobin and breast cancer survival was
      investigated using univariate and multivariate survival analyses. Plakoglobin may
      be a molecule functioning as a double-edge sword. Loss of plakoglobin expression
      leads to increased motility of epithelial cells, thereby promoting epithelial
      mesenchymal transition and further metastasis of cancer. However, studies also
      show that plakoglobin can function as an oncogene. High expression of plakoglobin
      results in clustered tumor cells in circulation with high metastatic potential in
      breast cancer and shortened patient survival. Plakoglobin may be a potential
      prognostic biomarker that can be exploited to develop as a therapeutic target for
      breast cancer. 

PMID- 25957596
TI  - Inhibitory Effect of Fluoride on Na+,K+ ATPase Activity in Human Erythrocyte
      Membrane.
AB  - The present study was performed to evaluate the role of long-term consumption of
      excessive fluoride on electrolyte homeostasis and their transporting mechanisms
      in erythrocytes of subjects afflicted with dental and skeletal fluorosis. A total
      of 620 adult (20-50 years) Indian residents participated in this study: 258 men
      and 242 women exposed to high concentrations of fluoride and 120 age and gender
      matched control subjects. Erythrocytes were isolated from blood samples, washed,
      and used for the estimation of intraerythrocyte sodium and potassium
      concentrations. Na+,K+ ATPase activity was determined spectrophotometrically from
      a ghost erythrocyte membrane prepared by osmotic lysis. Erythrocyte analytes were
      correlated with the water and serum fluoride concentrations by Pearson's
      bivariate correlation and regression analysis. Results indicated a significant
      increase in intraerythrocyte sodium (F=14306.265, P<0.0001) in subjects from
      endemic fluorosis study groups as compared to controls. A significant (P<0.05)
      positive correlation of intracellular sodium was found with water and serum
      fluoride concentrations. Mean concentration of intraerythrocytic potassium ions
      showed significant reduction (F=9136.318, P<0.0001) in subjects exposed to
      fluoride. A significant (P<0.05) negative correlation of potassium ions was noted
      with water and serum fluoride concentrations. Na+,K+ ATPase activity was
      significantly declined (F=1572.763, P<0.0001) in subjects exposed to fluoride. A
      significant (P<0.05) inverse relationship of Na+,K+ ATPase activity was revealed
      with water and serum fluoride concentrations.

PMID- 25957597
TI  - Selenium Content in the Liver of Wistar Rats Fed Diets of Different Fatty Acid
      Quality.
AB  - The purpose of this work was to measure the amounts of selected mineral elements
      (sodium, calcium, iron, selenium, magnesium, zinc, copper, and manganese) in the
      liver of Wistar rats and evaluate possible correlations between the levels of
      these minerals and the lipid metabolism in the studied animals. Three
      experimental groups each containing six Wistar rats were designed. Each group was
      fed a different diet. The control group was fed a diet prepared with fresh
      soybean oil and named control group--CG. The second group (named experimental
      group B--EGB) and third group (named experimental group C--EGC) were fed a diet
      containing soybean oil that had been used to fry different foods for four or ten
      cycles, respectively. The mineral elements in Wistar rat livers were measured by
      inductively coupled plasma optical emission spectrometry (ICP OES). Only the
      elements calcium and selenium differed significantly between the control and
      experimental groups. There was a significant reduction of 33% for Ca and 41% for
      Se in the EGB in comparison to the control group. The reduction in mineral
      concentration, especially Se, is the result of interactions with fatty acid
      metabolism. The animals in the EGC exhibited more intracytoplasmic accumulation
      of fat and more intense vasodilatation, in relation to the other groups.
      Collectively, evidence hereby collected suggests that impaired dietary lipid
      quality in otherwise balanced diets can reduce hepatic Se levels and potentially
      harm liver function.

PMID- 25957598
TI  - ADHD symptomatology is best conceptualized as a spectrum: a dimensional versus
      unitary approach to diagnosis.
AB  - The aim of this paper is to build a case for the utility of conceptualizing ADHD,
      not as a unitary disorder that contains several subtypes, but rather as a marker
      of impairment in attention and/or impulsivity that can be used to identify one of
      several disorders belonging to a spectrum. The literature will be reviewed to
      provide an overview of what is known about ADHD in terms of heterogeneity in
      symptomatology, neuropsychology, neurobiology, as well as comorbidity with other
      diseases and treatment options. The data from these areas of research will be
      critically analyzed to support the construct of a spectrum of disorders that can
      capture the great variability that exists between individuals with ADHD and can
      discriminate between separate disorders that manifest similar symptoms. The
      symptoms associated with ADHD can be viewed as dimensional markers that point to
      a spectrum of related disorders that have as part of their characteristics
      impairments of attention and impulsivity. The spectrum can accommodate
      symmetrically and asymmetrically comorbid psychiatric disorders associated with
      ADHD as well as the wide heterogeneity known to be a part of the ADHD disorder.
      Individuals presenting with impairments associated with ADHD should be treated as
      having a positive marker for a spectrum disorder that has as part of its
      characteristics impairments of attention and/or impulsivity. The identification
      of impairment in attention and/or impulsivity should be a starting point for
      further testing rather than being an endpoint of diagnosis that results in
      pharmacological treatment that may or may not be the optimal therapy. Rather than
      continuing to attribute a large amount of heterogeneity in symptom presentation
      as well as a high degree of symmetric and asymmetric comorbidity to a single
      disorder, clinical evaluation should turn to the diagnosis of the type of
      attentional deficit and/or impulsivity an individual has in order to colocate the
      individual's disorder on a spectrum that captures the heterogeneity in
      symptomatology, the symmetrical and asymmetrical comorbidity, as well as
      subthreshold presentation and other variants often worked into the disorder of
      ADHD. The spectrum model can accommodate not only the psychophysiological
      profiles of patients, but is also consistent with what is known about the
      functional heterogeneity of the prefrontal cortex as well as the construct that
      cognitive processes are supported by overlapping and collaborative networks. 

PMID- 25957599
TI  - The association of emotional lability and emotional and behavioral difficulties
      among children with and without ADHD.
AB  - Children with ADHD often demonstrate a pattern of emotional lability
      characterized by sudden and intense shifts in affect. Emotional lability has been
      linked to emotional and behavioral problems in children with and without ADHD,
      but few studies have examined emotional lability over time. This study examined
      the effects of emotional lability over time on the behavioral and emotional
      difficulties of children with and without ADHD using an ecological momentary
      assessment (EMA) methodology. One hundred and two children aged 8-12 years (56
      with ADHD and 46 without ADHD) and their parents completed baseline measures of
      the children's behavioral and emotional difficulties. Parents then completed a 28
      day 3-times daily EMA assessment protocol to rate their child's emotional
      lability. Results suggested that emotional lability was associated with
      internalizing and/or externalizing diagnoses independent of ADHD diagnostic
      status, but was not directly associated with ADHD. Hierarchical regression
      analyses supported ADHD diagnostic status as a moderator of the association of
      greater EMA-derived emotional lability with children's behavioral difficulties,
      such that greater emotional lability was associated with greater behavioral
      difficulties among children with ADHD but not among children without ADHD.
      Results indicated that greater emotional lability was directly linked with
      greater emotional difficulties and that this relation was not moderated by ADHD
      diagnostic status. Overall, this study suggested that emotional lability is
      related to emotional difficulties independent of ADHD, but is differentially
      related to behavioral difficulties among children with and without ADHD. 

PMID- 25957600
TI  - Regulatory role of guanine nucleotide exchange factor (GEF) Dock180
      phosphorylation on Tyr/Ser in mediation of gastric mucosal Rac1 activation in
      response to Helicobacter pylori and ghrelin.
AB  - A small GTPase, Rac1, is recognized as an important modulator of the inflammatory
      responses to bacterial lipopolysaccharide (LPS) by affecting the processes of
      phospholipase C activation. The activation of Rac1 involves the exchange of GDP
      for GTP and is catalyzed by the guanine nucleotide exchange factors (GEFs). Here,
      we report on the gastric mucosal GEF, Dock180, activation in response to H.
      pylori PS, and the hormone, ghrelin. We show that stimulation of gastric mucosal
      cells with the LPS leads to up-regulation in Dock180 phosphorylation on Tyr and
      Ser that is accompanied by a massive rise in Rac1-GTP level, while the effect of
      ghrelin, manifested by a drop in Dock180 phosphorylation on Ser, is associated
      with a decrease in Rac1-GTP formation. Furthermore, we demonstrate that
      phosphorylation on Tyr remains under the control of the Src family protein
      tyrosine kinases (SFK-PTKs), and is accompanied by Dock180 membrane
      translocation, while phosphorylation of the membrane-localized Dock180 on Ser
      represents the stimulatory contribution of protein kinase Cdelta (PKCdelta) to
      Dock180 activation. Moreover, we reveal that the interaction between Dock180 and
      PKCdelta is dependent on Dock180 Tyr phosphorylation as well as the activity of
      PKCdelta. Thus, our findings point to the involvement of PKCdelta in the LPS
      induced up-regulation of Dock180 activation, and suggest the modulatory mechanism
      of ghrelin influence on the gastric mucosal inflammatory responses to H. pylori. 

PMID- 25957601
TI  - Effect and timing of non-surgical treatment prior to periodontal regeneration: a
      systematic review.
AB  - OBJECTIVES: The aim of this systematic review was to assess the study design and
      reporting of studies on periodontal regeneration, with respect to the effect of
      the provision of non-surgical periodontal therapy (NSPT) before surgery.
      MATERIALS AND METHODS: A systematic search of the literature was conducted for
      studies on periodontal regeneration on Medline and EMBASE, complemented by a
      manual search. Initially, 3310 potentially eligible articles were identified.
      RESULTS: A total of 293 studies were included in the review. Nearly 10% of
      studies did not include NSPT in the study protocol before regenerative surgery,
      while 14% of papers did not report this aspect. Seventy-six percent of studies
      reported that non-surgical subgingival debridement was performed before
      periodontal surgery (2 weeks to 6 months before surgery according to the
      different studies). However, no papers reported clinical and radiographic data
      before and after NSPT prior to periodontal surgery. Only 45% of papers reported
      timing of reassessment following NSPT, prior to proceeding with regenerative
      surgery. CONCLUSIONS: This review highlights the lack of reporting information on
      non-surgical periodontal therapy prior to periodontal regenerative surgery,
      calling for a revision of the current clinical protocols and of the study designs
      of periodontal regenerative surgery studies. CLINICAL RELEVANCE: Periodontal
      regenerative surgery protocols should take into account the possible effects of
      non-surgical periodontal therapy in the clinical and radiographic healing of
      intrabony defects.

PMID- 25957603
TI  - Fluoroscopic control allows for precise tunnel positioning in MPFL
      reconstruction.
AB  - PURPOSE: In MPFL reconstruction, anatomical graft positioning is required to
      restore physiological joint biomechanics and patellofemoral stability.
      Considerable rates of non-anatomical femoral tunnel placement exist. The purpose
      of this study was to analyse whether intraoperative fluoroscopic control is
      applicable to reduce variability of femoral tunnel positioning. METHODS: Femoral
      tunnel positions of 116 consecutive MPFL reconstructions applying intraoperative
      fluoroscopic images were analysed. Tunnel positions were determined by two
      independent observers according to Schottle's radiographic measurement method.
      Mean positions, standard deviations and ranges were calculated to determine the
      variability of the tunnel positions. Interclass correlation coefficient (ICC) was
      calculated. RESULTS: The mean anterior/posterior distances from the anatomical
      insertion of the MPFL to the centre of the femoral tunnel were 2.34 mm (range 0.0
      5.9 mm) and 1.7 mm (range 0.1-7.3 mm, SD 1.3) for proximal/distal deviations;
      95.7 % (111/116) of femoral tunnel positions were found to be within the
      anatomical insertion area defined by Schottle. Interobserver tunnel position
      measurements were highly reliable (ICC: depth 0.979; height 0.979). CONCLUSION:
      The study demonstrates that intraoperative fluoroscopic control is a feasible and
      effective method that enables to create reproducible and precise anatomical
      femoral tunnel positions in MPFL reconstruction. Accordingly, the routine use of
      intraoperative fluoroscopy can be recommended. Furthermore, the results indicate
      Schottle's method as a reliable method for intraoperative control and
      postoperative analysis of femoral tunnel positioning. LEVEL OF EVIDENCE: IV.

PMID- 25957602
TI  - Multidrug-related leukocytoclastic vasculitis raising suspicion of sexual
      homicide-things are not always what they seem.
AB  - Ambiguous findings during external examination of a deceased in combination with
      dubious autopsy findings can raise doubts concerning the manner and cause of
      death. We report the case of a 35-year-old female deceased who had suffered from
      a borderline personality and depressive disorder with suicidal ideation. At the
      death scene, the body showed massive facial swelling accompanied by complete
      reddening of the skin of the face, with patchy skin abrasions on the forehead and
      neck, and purple bruise-like discolorations distributed symmetrically over both
      shoulders, elbows, hands, hips, knees, lower legs, and feet, raising the
      suspicion of underlying massive external blunt force injury. Police investigators
      strongly suspected sexual homicide. At autopsy, dissection in layers revealed
      massive subcutaneous hemorrhages as the cause of the reddish skin discolorations.
      Toxicological analyses showed fatal levels of lamotrigine with additional proof
      of zopiclone, zolpidem, diphenhydramine, O-desmethylvenlafaxine, pregabalin,
      tramadol, and modafinil in venous blood. Histologically, both the macroscopically
      impressive purple skin changes with underlying bleeding into the subcutaneous
      tissue and the skin abrasions were due to leukocytoclastic vasculitis, a form of
      acute hypersensitivity vasculitis that was a reaction to the multiple therapeutic
      drugs that the woman had taken shortly before death. The manner of death was
      classified as suicide, and sexual homicide was ruled out. 

PMID- 25957604
TI  - Knee multi-ligament reconstruction: a historical note on the fundamental
      landmarks.
AB  - Several eminent surgeons made breakthroughs in knee surgery throughout the
      nineteenth and twentieth centuries. Before that, knee injuries were only treated
      conservatively and it was thanks to the progress made in the field of
      biomechanics and biology that new surgical treatments were proposed. The history
      of medicine recalls some illustrious surgeons such as Thomas Annandale and Mayo
      Robson who were the first to perform and describe their revolutionary experience
      regarding meniscal and anterior cruciate ligament surgery. Less famous are the
      forefathers of multi-ligament reconstructive surgery: the purpose of this paper
      was to shed some light on the pioneers of this particular field of orthopaedic
      practice, which is gaining increasing interest in current clinical practice.
      Level of evidence V. 

PMID- 25957606
TI  - Diagnosis and classification of chondral knee injuries: comparison between
      magnetic resonance imaging and arthroscopy.
AB  - PURPOSE: To compare the magnetic resonance imaging (MRI) findings of patients
      undergoing knee arthroscopy for chondral lesions. The hypothesis was that MRI
      displays low sensitivity in the diagnosis and classification of chondral
      injuries. METHODS: A total of 83 knees were evaluated. The MRIs were performed
      using the same machine (GE SIGNA HDX 1.45 T). The MRI results were compared with
      the arthroscopy findings, and an agreement analysis was performed. Thirty-eight
      of the 83 MRI exams were evaluated by another radiologist for inter-observer
      agreement analysis. These analyses were performed using the kappa (kappa)
      coefficient. RESULTS: The highest incidence of chondral injury was in the patella
      (14.4 %). The kappa coefficient was 0.31 for the patellar surface; 0.38 for the
      trochlea; 0.46 for the medial femoral condyle; 0.51 for the lateral femoral
      condyle; and 0.19 for the lateral plateau. After dividing the injuries into two
      groups (ICRS Grades 0-II and Grades III and IV), the following kappa coefficients
      were obtained as follows: 0.49 (patella); 0.53 (trochlea); 0.46 (medial femoral
      condyle); 0.43 (medial plateau); 0.67 (lateral femoral condyle); and 0.51
      (lateral plateau). The MRI sensitivity was 76.4 % (patella), 88.2 % (trochlea),
      69.7 % (medial femoral condyle), 85.7 % (medial plateau), 81.8 % (lateral femoral
      condyle) and 75 % (lateral plateau). Comparing the radiologists' evaluations, the
      following kappa coefficients were obtained as follows: 0.73 (patella); 0.63
      (trochlea); 0.84 (medial femoral condyle); 0.72 (medial plateau); 0.77 (lateral
      femoral condyle); and 0.91 (lateral plateau). CONCLUSION: Compared with
      arthroscopy, MRI displays moderate sensitivity for detecting and classifying
      chondral knee injuries. It is an important image method, but we must be careful
      in the assessment of patients with suspected chondral lesions. LEVEL OF EVIDENCE:
      III.

PMID- 25957605
TI  - Minimally invasive Oxford medial unicompartmental knee arthroplasty in young
      patients.
AB  - PURPOSE: Advanced knee arthritis in young patients is a challenging problem that
      may necessitate surgical treatment. There are few published studies of mobile
      bearing unicompartmental knee arthroplasty (UKA) in young patients, while
      indications have expanded to its use in this demanding patient group. METHODS:
      The clinical and radiographic results of the first 118 consecutive Oxford medial
      UKAs (OUKA) using a minimally invasive technique (phase 3) in 101 patients 60
      years of age or younger at the time of surgery were evaluated. Median age at
      surgery was 57 (25-60) years. Kaplan-Meier survivorship analysis was used to
      estimate implant survival. RESULTS: Mean time of follow-up evaluation was five
      (SD 1.6) years. At final follow-up, three patients (three knees) had died, and
      two patients (three knees) were lost to follow-up. Five knees were revised: three
      for unexplained pain, one for early infection and one for bearing fracture. There
      was one impending revision for progression of osteoarthritis in the lateral
      compartment. The radiographic review demonstrated that 5 % of the knees had
      progressive arthritis in the lateral knee compartment, of those 2 % with full
      joint space loss and pain. The Kaplan-Meier survival analysis, using revision for
      any reason as the endpoint, estimated the five-year survival rate at 97 % (95 %
      CI 91-99). Ninety-six per cent of the non-revised patients were satisfied with
      the outcome, and 4 % were dissatisfied. The mean Oxford knee score was 41 (SD 7),
      with 6 % of the knees having a poor result. The mean AKSS was 89 (SD 14), mean
      flexion was 129 degrees  (SD 13) and the mean UCLA score was 6.8 (SD 1.5).
      CONCLUSION: Minimally invasive Oxford medial UKA was reliable and effective in
      this young and active patient cohort providing high patient satisfaction at mid
      term follow-up. Progressive arthritis in the lateral knee compartment was a
      relevant failure mode in this age group. Most revisions were performed for
      unexplained pain, while we did not find loosening or wear in any patient. LEVEL
      OF EVIDENCE: IV.

PMID- 25957608
TI  - Does increased femoral antetorsion predispose to cartilage lesions of the
      patellofemoral joint?
AB  - PURPOSE: The purpose of this study was to investigate whether there was a
      relationship between femoral neck antetorsion and the presence and pattern of
      osteoarthritis of the patellofemoral joint. It was hypothesized that an increased
      femoral neck antetorsion (1) correlates with osteoarthritic changes of the
      lateral facet of the patellofemoral joint and (2) correlates with an increased
      lateral trochlear height and a decreased sulcus angle. METHODS: Seventy-eight
      formalin-embedded cadaveric lower extremities from thirty-nine subjects with a
      median age of 74 years (range 60-88) were used. Surrounding soft tissues of the
      lower limb were removed. The femoral neck antetorsion was measured and referenced
      to the transepicondylar axis and the posterior condylar line. The height of the
      medial and lateral facet of the trochlea and the sulcus angle was measured. The
      location and the degree of patellofemoral cartilage degeneration were recorded. A
      Pearson's correlation analysis was performed to correlate the femoral neck
      antetorsion with the measured knee parameters. RESULTS: No significant
      correlation could be found between the femoral antetorsion and cartilage
      degeneration of the lateral patellofemoral joint (n.s.), the height of the
      lateral trochlea (n.s.) and the sulcus angle (n.s.). CONCLUSION: This study could
      not document that the femoral neck antetorsion and subsequent internal rotation
      of the distal femur correlated with the degree of degeneration of the lateral
      facet of the patellofemoral joint. Clinically, femoral internal rotation may play
      a minor role in the development of lateral patellofemoral joint degeneration.

PMID- 25957607
TI  - Do ground reaction forces during unilateral and bilateral movements exhibit
      compensation strategies following ACL reconstruction?
AB  - PURPOSE: The aims of the study were (1) to evaluate the leg asymmetry assessed
      with ground reaction forces (GRFs) during unilateral and bilateral movements of
      different knee loads in anterior cruciate ligament (ACL) reconstructed patients
      and (2) to investigate differences in leg asymmetry depending on the
      International Knee Documentation Committee Subjective Form (IKDC) in order to
      identify potential compensation strategies. METHODS: The knee function of 50 ACL
      reconstructed (patella tendon) patients was examined at 31 +/- 7 months after the
      surgery. GRFs were quantified during the sit-to-stand and stand-to-sit test, the
      step-up and step-down test, and the two- and one-leg vertical jump. Further, the
      IKDC score, the anterior-posterior knee laxity, and the concentric torque of the
      quadriceps and hamstring muscles were evaluated. RESULTS: Differences between the
      operated and non-operated leg were found in the knee laxity, the quadriceps
      torque, and GRFs. The patients with low IKDC scores demonstrated greater leg
      asymmetries in GRFs compared to the patients with high IKDC scores. CONCLUSIONS:
      ACL reconstructed patients showed GRF asymmetries during unilateral and bilateral
      movements of different knee loads. Three compensation strategies were found in
      patients with low subjective knee function: (1) a reduced eccentric load, (2) an
      inter-limb compensation during bilateral movements, and (3) the avoidance of high
      vertical impact forces. These compensation strategies may be indicative of a
      protective adaptation to avoid excessive ACL strain. GRF measurements are
      practicable and efficient tools to identify individual compensation strategies
      during early rehabilitation.

PMID- 25957609
TI  - Intra-articular peroneal nerve incarceration following multi-ligament knee
      injury.
AB  - Knee dislocation with a common peroneal nerve injury is a serious problem. A case
      of multi-ligamentous knee injury with the unusual and interesting finding of a
      common peroneal nerve rupture incarcerated within the knee joint is presented.
      MRI and arthroscopic images are used to document this occurrence. To date, there
      are no published reports of a similar finding in the English orthopaedic
      literature. Level of evidence IV. 

PMID- 25957610
TI  - Reconstruction of the lateral ulnar collateral ligament of the elbow: a
      comparative biomechanical study.
AB  - PURPOSE: Posterolateral rotatory instability (PLRI) of the elbow is the result of
      an insufficient lateral collateral ligament complex (LCLC). Single-bundle
      reconstruction of the lateral ulnar collateral ligament (LUCL) represents the
      standard treatment method for chronic PLRI. However, cases of recurrent
      instability after LUCL reconstruction have been reported. The dual-reconstruction
      procedure has been described to anatomically restore the LUCL as well as the
      radial collateral ligament (RCL). It was hypothesized that anatomic
      reconstruction of the LCLC provides increased stability compared with the
      conventional technique. METHODS: Posterolateral rotatory displacement was
      assessed in eight fresh-frozen human elbows with a maximum load of 20 N. Data
      were obtained in 0 degrees , 30 degrees , 60 degrees , 90 degrees  and 120
      degrees  of elbow flexion for native specimens, dissected LCLC and three
      reconstruction methods: (1) single-bundle LUCL reconstruction, (2) single-bundle
      LUCL reconstruction with RCL augmentation, (3) dual-reconstruction technique
      (LUCL + RCL). RESULTS: All reconstruction methods were able to sufficiently
      restore posterolateral rotatory stability of the elbow over the full range of
      motion. There were no significant differences between the intact specimens and
      either reconstruction method. Dissection of the LCLC significantly increased PLRI
      compared with the other groups (p < 0.001). CONCLUSION: The less invasive dual
      reconstruction technique is confirmed as a safe procedure for anatomic LCLC
      reconstruction. Primary stability is equal, yet not superior to conventional LUCL
      reconstruction. Hence, this biomechanical study does not confirm the hypothesis
      that more anatomic reconstruction techniques could reduce the risk of recurrent
      instability when compared to conventional LUCL reconstruction.

PMID- 25957611
TI  - Clinically relevant anatomy and what anatomic reconstruction means.
AB  - BACKGROUND: Within the past 20 years, knee ligament injuries have been
      increasingly reported in the literature to be treated with anatomic
      reconstructions over soft tissue advancements or sling-type procedures to
      recreate the native anatomy and restore knee function. Historically, early
      clinician scientists published on the qualitative anatomy of the knee, which
      provided a foundation for the initial knee biomechanical studies in the
      nineteenth and twentieth centuries. Similarly, the work of early sports medicine
      orthopaedic clinician scientists in the late twentieth century formed the basis
      for the quantitative anatomic and functional robotic biomechanical studies found
      currently in the sports medicine orthopaedic literature. The development of an
      anatomic reconstruction first requires an appreciation of the quantitative
      anatomy and function of each major stabilizing component of the knee. PURPOSE:
      This paper provides an overview of the initial qualitative anatomic studies from
      which the initial knee ligament surgeries were based and expands to recent
      detailed quantitative studies of the major knee ligaments and the renewed recent
      focus on anatomic surgical reconstructions. CONCLUSIONS: Anatomic repairs and
      reconstructions of the anterior cruciate ligament, posterior cruciate ligament,
      medial collateral ligament and posterolateral corner attempt to restore knee
      function by rebuilding or restoring the native anatomy. The basis of anatomic
      reconstruction techniques is a detailed understanding of quantitative knee
      anatomy. Additionally, an appreciation of the function of each component is
      necessary to ensure surgical success. LEVEL OF EVIDENCE: V.

PMID- 25957612
TI  - All-polyethylene tibial components generate higher stress and micromotions than
      metal-backed tibial components in total knee arthroplasty.
AB  - PURPOSE: Most total knee arthroplasty tibial components are metal-backed, but an
      alternative tibial component made entirely of polyethylene (all-polyethylene
      design) exists. While several clinical studies have shown that all-poly design
      performs similarly to the metal-backed, the objective of this study is to perform
      a biomechanical comparison. METHODS: Loads, constraints and geometries during a
      squat activity at 120 degrees  of flexion were obtained from a validated
      musculoskeletal model and applied to a finite element model. Stresses in the
      tibia and micromotions at the bone-implant interface were evaluated for several
      implant configurations: (1) three different thicknesses of the cement penetration
      under the baseplate (2, 3 and 4 mm), (2) the presence or absence of a cement
      layer around the stem of the tibial tray and (3) three different bone conditions
      (physiological, osteopenic and osteoporotic bone). RESULTS: All-polyethylene
      tibial components resulted in significantly higher (p < 0.001) and more uneven
      stress distributions in the cancellous bone under the baseplate (peak difference:
      +128.4 %) and fivefold increased micromotions (p < 0.001). Performance of both
      implant designs worsened with poorer bone quality with peaks in stress and
      micromotion variations of +40.8 and +54.0 %, respectively (p < 0.001).
      Performance improvements when the stem was cemented were not statistically
      significant (n.s.). CONCLUSION: The metal-backed design showed better
      biomechanical performance during a squat activity at 120 degrees  of flexion
      compared to the all-polyethylene design. These results should be considered when
      selecting the appropriate tibial component for a patient, especially in the
      presence of osteoporotic bone or if intense physical activity is foreseen.

PMID- 25957613
TI  - Comparison of Brostrom technique, suture anchor repair, and tape augmentation for
      reconstruction of the anterior talofibular ligament.
AB  - PURPOSE: Recently, tape augmentation for Brostrom repair has been introduced in
      order to improve the primary stability of the reconstructed anterior talofibular
      ligament (ATFL). The biomechanical effect of tape augmentation suture anchor (SA)
      repair is not known yet. The aim of the present study was to compare construct
      stability of the traditional Brostrom (TB) repair compared with a stand alone SA
      repair (SutureTak, Arthrex) and SA repair combined with tape augmentation
      (InternalBrace, Arthrex) internal brace (IB) of the ATFL. METHODS: Eighteen fresh
      frozen human anatomic lower leg specimens were randomly assigned to three
      different groups: TB group, SA group, and IB augmentation group. In vivo torsion
      conditions in ankle sprain were carried out quasi-statically (0.5 degrees /s).
      Torque (Nm) required to resist as well as the rotary displacement ( degrees ) of
      the load frame was recorded. Intergroup differences for age, bone mineral density
      (BMD), angle at failure, and torque at failure were analysed using ANOVA.
      RESULTS: In the TB group, ATFL reconstruction failed at an angle of 24.1 degrees
      , in the SA group failure occurred at 35.5 degrees , and in the IB group it
      failed at 46.9 degrees  (p = 0.02). Torque at failure reached 5.7 Nm for the TB
      repair, 8.0 Nm for the SA repair, and 11.2 Nm for the IB group (p = 0.04). There
      was no correlation between angle at ATFL failure, torque at failure, and BMD for
      the SA or IB groups. CONCLUSION: The present biomechanical study reveals
      statistically superior performance in terms of angle at failure as well as
      failure torque for the IB group compared to the other reconstruction methods. BMD
      did not influence the construct stability in the SA repair groups.

PMID- 25957614
TI  - New insights on the role of the insular cortex and habenula in OSA.
AB  - PURPOSE: Abnormal structure or function in the central nervous system (CNS) can
      also affect obstructive sleep apnea (OSA). Because human afferent and motor
      pathways that regulate apnea are still poorly understood, it is not possible to
      modify the behavior of motor neurons to control airway function. The purpose of
      this article is to clear the central control mechanism of genioglossus (GG) and
      to discuss how altered activity in the limbic system and its related structures
      might affect OSA development, in order to provide help for the treatment of this
      disease. METHODS: Functional magnetic resonance imaging (fMRI) data from previous
      studies on OSA-related brain damage in human beings plus the data from clinical
      and animal experiments are summarized. These articles are overviewed to discuss
      the roles of the limbic system-the insular cortex (Ic), the habenula (Hb), and
      CNS-in the pathogenesis and mechanisms of OSA. RESULTS: The Ic, which relays
      signals through the Hb, may play a role in OSA because activating the Ic causes
      the Hb to suppress activity of the raphe nucleus (RN), resulting in lower levels
      of 5-hydroxytryptamine (5-HT) that decreases the muscle tone of the GG. This
      leads to airway collapse. CONCLUSIONS: The Ic may be an important region in the
      development of OSA. Altered activity in the limbic system and its related
      structures could also be associated with OSA.

PMID- 25957615
TI  - Effect of APAP and heated humidification with a heated breathing tube on
      adherence, quality of life, and nasopharyngeal complaints.
AB  - PURPOSE: Positive airway pressure (PAP) therapy adherence can be affected by
      rhinitis sicca and xerostomia complaints. Additional heated humidification (HH)
      is the appropriate method when such complaints arise. The aim of this study was
      to determine if HH with a supplementary heated breathing tube can increase
      adherence, reduce subjective nasopharyngeal complaints (NPC), and improve
      sleepiness (ESS: Epworth Sleepiness Scale) and quality of life (FOSQ: Functional
      Outcome of Sleep Questionnaire). METHODS: We subdivided 72 obstructive sleep
      apnea (OSA) patients into two groups before therapy initiation. The NPC risk
      group consists of subjects with NPC and the low-risk group without. The risk
      group was identified by a score of >9 in a 5-item 25-point NPC questionnaire and
      pathological ESS. All patients were eligible for automatic CPAP devices (APAP),
      which were randomly configured with or without HH during 6 weeks. RESULTS: The
      adherence differences with and without HH were not significant in the NPC risk
      group (330 +/- 103 vs. 281 +/- 118 min/night) and in the low-risk group (330 +/-
      116 vs. 321 +/- 89). NPC and ESS scores in the risk group were both significantly
      reduced with HH. Daily function (FOSQ) in the risk group was significantly
      improved with HH (90.0 +/- 11.9 vs. 82.0 +/- 12.0 (p < 0.05)). CONCLUSION: HH
      showed a tendency to improve APAP adherence. The adherence in both groups was
      quite high, and for that reason, it is difficult to show a statistically
      significant effect. A differentiation into NPC risk groups before starting PAP
      treatment is useful. HH reduces side effects and sleepiness and improves quality
      of life in an NPC risk group.

PMID- 25957616
TI  - What can impulse oscillometry and pulmonary function testing tell us about
      obstructive sleep apnea: a case-control observational study?
AB  - PURPOSE: This study aims to determine whether functional residual capacity (FRC)
      in obese patients with obstructive sleep apnea (OSA) decreases more than in
      patients without OSA because of decreased outward recoil from chest wall mass
      loading as well as increased lung inward recoil. METHODS: Subjects who were
      overweight and obese to various degrees with normal spirometric values underwent
      overnight polysomnography to determine the presence or absence of OSA and were
      labeled as cases or controls. Lung volume and respiratory mechanical properties
      were measured by plethysmograph and impulse oscillometry, respectively. RESULTS:
      A total of 76 men and 31 women were diagnosed with OSA (cases); 64 men and 33
      women without OSA were confirmed as controls. Expiratory reserve volume and FRC
      were significantly decreased in cases compared with controls. Respiratory
      impedance and resistance at 5 Hz were significantly higher in cases than in
      controls, although reactance at low frequencies was significantly lower in cases
      than in controls. Reactance at 5 Hz (Xrs5) was found to be independently highly
      correlated with the severity of OSA as defined by the Apnea-Hypopnea Index and
      was significantly correlated with FRC. CONCLUSIONS: FRC is significantly
      decreased in overweight or obese patients with OSA compared with those without
      OSA, which may be attributed to an increase in lung elastic recoil. The stronger
      correlation between Xrs5 and OSA severity might indicate upper airway stenosis,
      and abnormally increased lung elastic recoil may contribute to OSA.

PMID- 25957617
TI  - Sleep disorders in pregnancy and their association with pregnancy outcomes: a
      prospective observational study.
AB  - PURPOSE: Sleep disturbances such as insomnia, nocturnal awakenings, restless legs
      syndrome, habitual snoring, and excessive daytime sleepiness are frequent during
      pregnancy, and these have been linked to adverse maternal and fetal outcomes.
      METHODS: A prospective observational study was performed in high-risk Indian
      pregnant women. We used modified Berlin questionnaire (MBQ), Pittsburgh sleep
      quality index (PSQI), International Restless Legs Syndrome Study Group 2011
      criteria, and Epworth sleepiness scale to diagnose various sleep disorders, such
      as symptomatic OSA, poor sleep quality and insomnia, RLS, and excessive daytime
      sleepiness, respectively, in successive trimesters of pregnancy. Outcome
      variables of interest were development of gestational hypertension (GH),
      gestational diabetes mellitus (GDM), and cesarean delivery (CS); the Apgar
      scores; and low birth weight (LBW). The relationship between sleep disorders and
      outcomes was explored using logistic regression analysis. RESULTS: Outcome data
      were obtained in 209 deliveries. As compared to nonsnorers, women who reported
      snoring once, twice, and thrice or more had odds ratios for developing GH-4.0 (95
      % CI 1.3-11.9), 1.5 (95 % CI 0.5-4.5), and 2.9 (95 % CI 1.0-8.2) and for
      undergoing CS-5.3 (95 % CI 1.7-16.3), 4.9 (95 % CI 1.8-13.1), and 5.1 (95 % CI
      1.9-14.9), respectively. Pregnant women who were persistently positive on MBQ had
      increased odds for GH and CS. CONCLUSIONS: Snoring and high-risk MBQ in pregnant
      women are strong risk factors for GH and CS. In view of the significant morbidity
      and health care costs, simple screening of pregnant women with questionnaires
      such as MBQ may have clinical utility.

PMID- 25957618
TI  - Poor sleep quality associated with obesity in men.
AB  - OBJECTIVE: The objective of this study is to examine the association between
      sleep quality and obesity status. METHODS: A cross-sectional study of 3225
      Chinese participants aged 18 to 65 years was conducted in Beijing in 2007. Body
      mass index (BMI) was classified according to the Working Group on Obesity in
      China, and sleep quality was assessed by the modified Pittsburg Sleep Quality
      Index questionnaire. Logistic regression models were applied to estimate the odds
      ratios (OR) and 95 % CIs of obesity by sleep quality adjusted for potential
      confounders. Two sets of potential confounders were used in the adjusted models.
      Model 1 was adjusted for sex and age. Model 2 was further adjusted for education
      level, occupation, marriage status, smoking, alcohol consumption, body pain, and
      health status. RESULTS: Poor sleep quality was significantly negatively
      associated with overweight/obesity in men but not in women. Additional adjustment
      for education level, occupation, marriage status, smoking, alcohol consumption,
      body pain, and health status did not attenuate the association (OR = 1.41 with 95
      % CI 1.03-1.93; P < 0.05) among men. The adjusted OR per sleep quality score hour
      was 1.07 (1.01-1.14) for overweight/obesity, suggesting that for one score
      increase in sleep quality, obesity/overweight risk increased by 7 % in men.
      CONCLUSION: Sleep quality was negatively associated with overweight/obesity in
      Chinese men but not in women.

PMID- 25957619
TI  - The molecular diversity scope of 1,3-indandione in organic synthesis.
AB  - Indandione is an important starting material that has drawn great attention in
      various organic transformations because of its attributes, such as low cost, easy
      to handle and eco-friendliness generally affording the corresponding products in
      excellent yields. In this review, we summarize recent data describing the most
      important MCRs reactions in which one of the starting materials is indandione.
      This review will also present two-, three-, four-, and five-component and one-pot
      reactions for the functionalization of indandione with the to increase awareness
      on the versatility of using this compound among organic chemists. 

PMID- 25957620
TI  - Store-operated calcium entry compensates fast ER calcium loss in resting
      hippocampal neurons.
AB  - The endoplasmic reticulum (ER) acts as a dynamic calcium store and is involved in
      the generation of specific patterns of calcium signals in neurons. Calcium is
      mobilized from the ER store by multiple signaling cascades, and neuronal activity
      is known to regulate ER calcium levels. We asked how neurons regulate ER calcium
      levels in the resting state. Direct ER calcium imaging showed that ER calcium was
      lost quite rapidly from the somatic and dendritic ER when resting neurons were
      transiently kept under calcium-free conditions. Interestingly, free ER and free
      cytosolic calcium was lost continuously across the plasma membrane and was not
      held back in the cytosol, implying the presence of a prominent calcium influx
      mechanism to maintain ER calcium levels at rest. When neurons were treated
      acutely with inhibitors of store-operated calcium entry (SOCE), an immediate
      decline in ER calcium levels was observed. This continuous SOCE-like calcium
      entry did not require the activation of a signaling cascade, but was rather a
      steady-state phenomenon. The SOCE-like mechanism maintains medium-high ER calcium
      levels at rest and is essential for balanced resting calcium levels in the ER and
      cytosol. 

PMID- 25957623
TI  - Western Juniper Management: Assessing Strategies for Improving Greater Sage
      grouse Habitat and Rangeland Productivity.
AB  - Western juniper (Juniperus occidentalis subsp. occidentalis) range expansion into
      sagebrush steppe ecosystems has affected both native wildlife and economic
      livelihoods across western North America. The potential listing of the greater
      sage-grouse (Centrocercus urophasianus) under the U.S. Endangered Species Act has
      spurred a decade of juniper removal efforts, yet limited research has evaluated
      program effectiveness. We used a multi-objective spatially explicit model to
      identify optimal juniper removal sites in Northeastern California across weighted
      goals for ecological (sage-grouse habitat) and economic (cattle forage
      production) benefits. We also extended the analysis through alternative case
      scenarios that tested the effects of coordination among federal agencies,
      budgetary constraints, and the use of fire as a juniper treatment method. We
      found that sage-grouse conservation and forage production goals are somewhat
      complementary, but the extent of complementary benefits strongly depends on
      spatial factors and management approaches. Certain management actions
      substantially increase achievable benefits, including agency coordination and the
      use of prescribed burns to remove juniper. Critically, our results indicate that
      juniper management strategies designed to increase cattle forage do not
      necessarily achieve measurable sage-grouse benefits, underscoring the need for
      program evaluation and monitoring.

PMID- 25957621
TI  - The Cholangiopathies.
AB  - Cholangiocytes (ie, the epithelial cells that line the bile ducts) are an
      important subset of liver cells. They are actively involved in the modification
      of bile volume and composition, are activated by interactions with endogenous and
      exogenous stimuli (eg, microorganisms, drugs), and participate in liver injury
      and repair. The term cholangiopathies refers to a category of chronic liver
      diseases that share a central target: the cholangiocyte. The cholangiopathies
      account for substantial morbidity and mortality given their progressive nature,
      the challenges associated with clinical management, and the lack of effective
      medical therapies. Thus, cholangiopathies usually result in end-stage liver
      disease requiring liver transplant to extend survival. Approximately 16% of all
      liver transplants performed in the United States between 1988 and 2014 were for
      cholangiopathies. For all these reasons, cholangiopathies are an economic burden
      on patients, their families, and society. This review offers a concise summary of
      the biology of cholangiocytes and describes a conceptual framework for
      development of the cholangiopathies. We also present the recent progress made in
      understanding the pathogenesis of and how this knowledge has influenced therapies
      for the 6 common cholangiopathies-primary biliary cirrhosis, primary sclerosing
      cholangitis, cystic fibrosis involving the liver, biliary atresia, polycystic
      liver disease, and cholangiocarcinoma-because the latest scientific progress in
      the field concerns these conditions. We performed a search of the literature in
      PubMed for published papers using the following terms: cholangiocytes, biliary
      epithelia, cholestasis, cholangiopathy, and biliary disease. Studies had to be
      published in the past 5 years (from June 1, 2009, through May 31, 2014), and non
      English studies were excluded.

PMID- 25957624
TI  - Shaping the Herders' "Mental Maps": Participatory Mapping with Pastoralists' to
      Understand Their Grazing Area Differentiation and Characterization.
AB  - Understanding the perception of environmental resources by the users is an
      important element in planning its sustainable use and management. Pastoralist
      communities manage their vast grazing territories and exploit resource
      variability through strategic mobility. However, the knowledge on which
      pastoralists' resource management is based and their perception of the grazing
      areas has received limited attention. To improve this understanding and to
      document this knowledge in a way that can be communicated with 'outsiders', we
      adopted a participatory mapping approach using satellite imagery to explore how
      Borana pastoralists of southern Ethiopia differentiated and characterized their
      grazing areas. The Borana herders conceptualized their grazing areas as set of
      distinctive grazing units each having specific names and characteristics. The
      precise location and the borders of each grazing unit were identified on the
      satellite image. In naming of the grazing units, the main differentiating
      criteria were landforms, vegetation types, prevalence of wildlife species, and
      manmade features. Based on the dominant soil type, the grazing units were
      aggregated into seasonal grazing areas that were described using factors such as
      soil drainage properties, extent of woody cover, main grass species, and
      prevalence of ecto-parasites. Pastoralists ranking of the seasonal grazing areas
      according to their suitability for cattle grazing matched with vegetation
      assessment results on the abundance of desirable fodder varieties. Approaching
      grazing area differentiation from the pastoralists' perspectives improves the
      understanding of rangeland characteristics that pastoralists considered important
      in their grazing management and visualization of their mental representation in
      digital maps eases communication of this knowledge.

PMID- 25957622
TI  - Increased DNA damage and repair deficiency in granulosa cells are associated with
      ovarian aging in rhesus monkey.
AB  - PURPOSE: Ovarian aging is closely tied to the decline in ovarian follicular
      reserve and oocyte quality. During the prolonged reproductive lifespan of the
      female, granulosa cells connected with oocytes play critical roles in maintaining
      follicle reservoir, oocyte growth and follicular development. We tested whether
      double-strand breaks (DSBs) and repair in granulosa cells within the follicular
      reservoir are associated with ovarian aging. METHODS: Ovaries were sectioned and
      processed for epi-fluorescence microscopy, confocal microscopy, and
      immunohistochemistry. DNA damage was revealed by immunstaining of gammaH2AX foci
      and telomere damage by gammaH2AX foci co-localized with telomere associated
      protein TRF2. DNA repair was indicated by BRCA1 immunofluorescence. RESULTS: DSBs
      in granulosa cells increase and DSB repair ability, characterized by BRCA1 foci,
      decreases with advancing age. gammaH2AX foci increase in primordial, primary and
      secondary follicles with advancing age. Likewise, telomere damage increases with
      advancing age. In contrast, BRCA1 foci in granulosa cells of primordial, primary
      and secondary follicles decrease with monkey age. BRCA1 positive foci in the
      oocyte nuclei also decline with maternal age. CONCLUSIONS: Increased DSBs and
      reduced DNA repair in granulosa cells may contribute to ovarian aging. Discovery
      of therapeutics that targets these pathways might help maintain follicle reserve
      and postpone ovarian dysfunction with age.

PMID- 25957626
TI  - Ketamine may be related to minor troponin elevations in children undergoing minor
      procedures in the ED.
AB  - OBJECTIVE: Ketamine is a dissociative anesthetic agent that has an increased
      frequency of usage in the last years particularly in emergency departments. In
      the present study, we aimed to determine whether ketamine is related to
      myocardial injury in children undergoing minor procedures. METHOD: Children
      younger than 18 years undergoing procedural sedation secondary to minor trauma
      composed the study population. Patients were administered ketamine with a dose of
      1.5 mg/kg via intravenous route. QT interval was measured by Bazett's formula,
      and QT dispersion was determined by taking the average of 3 different QT
      intervals. High-sensitive troponin levels were measured before and 3 hours after
      the ketamine administration. RESULTS: A total of 30 patients were included into
      the study. Study subjects had a median age of 2 years (interquartile range, 1-4
      years). There were 2 patients among the study patients who had troponin
      elevations 3 hours after the ketamine administrations. High-sensitive troponin
      levels of these 2 at the time of preketamine, 3, 5, and 24 hours after the
      ketamine administration were as follows: 5, 29, 15, and 5 ng/L and 3, 44, 41, and
      4 ng/L, respectively. There was no difference before and after the ketamine
      administration for the corrected QT intervals and QT dispersions. CONCLUSION:
      Ketamine may be related to minor troponin elevations in children undergoing
      procedural sedation without a permanent cardiac dysfunction.

PMID- 25957625
TI  - Safety and feasibility of the laryngeal tube when used by EMTs during out-of
      hospital cardiac arrest.
AB  - BACKGROUND: Ventilation is still one key element of advanced life support.
      Emergency medical technicians (EMTs) without training in advanced airway
      management usually use bag valve mask ventilation (BVM). Bag valve mask
      ventilation requires proper training and yet may be difficult and ineffective.
      Supraglottic airway devices, such as the laryngeal tube (LT), have been proposed
      as alternatives. Safety and feasibility are unclear if used by EMTs with limited
      training only. We compared efficacy of the LT to BVM for out-of-hospital cardiac
      arrest in a primarily volunteer-based emergency medical services. METHODS: This
      is a prospective multicenter observational cohort study. We compared safety
      (injuries and regurgitation) and feasibility (successful ventilation) in patients
      who received BVM, LT, or fallback to BVM after LT and controlled for potential
      confounders using logistic regression. RESULTS: A total of 517 cases were
      documented, 395 (76.7%) with LT, 74 (14.4%) with BVM, and 48 (9.3%) where EMTs
      fell back from LT to BVM. There was no difference between groups regarding
      demographics (71 +/- 17 years; 37% female) and initial rhythm (44% shockable).
      Placement of LT at first attempt was possible in 300 cases (76%), and at second
      attempt, in 91 cases (23%). Compared to BVM (22 cases [30%]), ventilation was
      more frequently successful with LT in 367 cases (93%; adjusted risk ratio, 3.1
      [95% confidence interval, 1.3-7.1]; P < .01) and less successful with LT to BVM
      in 7 cases (15%; 0.3 [0.1-0.7]; P = .01). Five injuries (1.3%) were documented.
      Regurgitation was observed 8 (11%), 22 (6%; P < .01), and 8 times (17%; P < .01),
      respectively. CONCLUSIONS: Use of the LT during out-of-hospital cardiac arrest by
      EMTs with only basic training appears safe and feasible. Compared to BVM, success
      rates were higher. Injuries were relatively rare.

PMID- 25957628
TI  - Male age and female mate choice in a synchronizing katydid.
AB  - In acoustically communicating species, females often evaluate the frequency
      content, signal duration and the temporal signal pattern to gain information
      about the age of the signaller. This is different in the synchronizing bush
      cricket Mecopoda elongata where females select males on the basis of relative
      signal timing in duets. In a longitudinal approach, we recorded songs of M.
      elongata males produced 2 weeks (young male) and 9 weeks (old male) after their
      ultimate moult. Signal timing of both age categories was studied in acoustic
      interactions, and female preference was investigated in choice situations. Young
      male chirps were significantly shorter and contained less energy compared to "old
      chirps". In mixed-age duets younger males timed their chirps as leader
      significantly more often. Females preferred the young male chirp when broadcast
      as leader over the old male chirp, but choice was random when the old male chirp
      was leader. This choice asymmetry was abolished after reducing the duration of
      the "old chirp". Results were mirrored in response of a bilateral pair of
      auditory neurons, where the asymmetry in spike count and first-spike latency
      correlated with behaviour. We suggest that older males may compensate their
      disadvantage in a more complex chorus situation. 

PMID- 25957627
TI  - Biomechanical force induces the growth factor production in human periodontal
      ligament-derived cells.
AB  - Although many reports have been published on the functional roles of periodontal
      ligament (PDL) cells, the mechanisms involved in the maintenance and homeostasis
      of PDL have not been determined. We investigated the effects of biomechanical
      force on growth factor production, phosphorylation of MAPKs, and intracellular
      transduction pathways for growth factor production in human periodontal ligament
      (hPDL) cells using MAPK inhibitors. hPDL cells were exposed to mechanical force
      (6 MPa) using a hydrostatic pressure apparatus. The levels of growth factor mRNA
      and protein were examined by real-time RT-PCR and ELISA. The phosphorylation of
      MAPKs was measured using BDTM CBA Flex Set. In addition, MAPKs inhibitors were
      used to identify specific signal transduction pathways. Application of
      biomechanical force (equivalent to occlusal force) increased the synthesis of
      VEGF-A, FGF-2, and NGF. The application of biomechanical force increased the
      expression levels of phosphorylated ERK and p38, but not of JNK. Furthermore, the
      levels of VEGF-A and NGF expression were suppressed by ERK or p38 inhibitor. The
      growth factors induced by biomechanical force may play a role in the mechanisms
      of homeostasis of PDL.

PMID- 25957629
TI  - Fingolimod induces the transition to a nerve regeneration promoting Schwann cell
      phenotype.
AB  - Successful regeneration of injured peripheral nerves is mainly attributed to the
      plastic behavior of Schwann cells. Upon loss of axons, these cells trans
      differentiate into regeneration promoting repair cells which provide trophic
      support to regrowing axons. Among others, activation of cJun was revealed to be
      involved in this process, initiating the stereotypic pattern of Schwann cell
      phenotype alterations during Wallerian degeneration. Nevertheless, the ability of
      Schwann cells to adapt and therefore the nerve's potential to regenerate can be
      limited in particular after long term denervation or in neuropathies leading to
      incomplete regeneration only and thus emphasizing the need for novel therapeutic
      approaches. Here we stimulated primary neonatal and adult rat Schwann cells with
      Fingolimod/FTY720P and investigated its impact on the regeneration promoting
      phenotype. FTY720P activated a number of de-differentiation markers including
      cJun and interfered with maturation marker and myelin expression. Functionally,
      FTY720P treated Schwann cells upregulated growth factor expression and these
      cells enhanced dorsal root ganglion neurite outgrowth on inhibitory substrates.
      Our results therefore provide strong evidence that FTY720P application supports
      the generation of a repair promoting cellular phenotype and suggest that
      Fingolimod could be used as treatment for peripheral nerve injuries and diseases.

PMID- 25957631
TI  - Relation between left atrial wall composition by late gadolinium enhancement and
      complex fractionated atrial electrograms in patients with persistent atrial
      fibrillation: influence of non-fibrotic substrate in the left atrium.
AB  - The complex fractioned atrial electrogram (CFAE) has been considered as the
      catheter ablation target of left atrium (LA) under persistent atrial fibrillation
      (PeAF). We evaluated the relation between the LA wall composition by late
      gadolinium enhancement cardiac magnetic resonance (LGE-CMR) and the CFAE in
      patients with PeAF. Forty-three patients underwent LGE-CMR and CFAE mapping
      before catheter ablation for PeAF. The LA wall substrates were classified into
      three: the fibrotic, intermediate, and normal substrates by using two thresholds
      of 2 standard deviation (2-SD) and 6-SD above the mean signal from the normal
      myocardium. For each of 12 preselected LA wall regions, the composition ratios
      (CRs) of fibrotic, indeterminate, and normal substrates were calculated as a
      percentage to the volume of LA wall region, and compared depending on the CFAE,
      respectively. The CR of normal substrate was significantly greater at the LA wall
      region with CFAE (52 +/- 38% vs. 20 +/- 28%, P < 0.01) than without CFAE. In
      contrast, the LA wall region with CFAE showed significantly lower CRs of
      intermediate substrate (39 +/- 34% vs. 57 +/- 31%, P < 0.01) and fibrotic
      substrate (7 +/- 17% vs. 21 +/- 24%, P < 0.01) than did the LA wall region
      without CFAE, respectively. Thus, the high CR (>18%) of normal substrate
      predicted the CFAE at the corresponding LA wall region with 71% sensitivity and
      62% specificity. In conclusion, the evaluation of LA wall normal substrate by LGE
      CMR might be useful to predict the CFAE occurrence before catheter ablation of
      PeAF.

PMID- 25957632
TI  - Whole exome sequencing and the clinician: we need clinical skills and functional
      validation in variant filtering.
AB  - Whole exome sequencing (WES) is a recently developed technique in genetics
      research that attempts to identify causative mutations in complex, undiagnosed
      genetic conditions. Causative mutations are usually identified after filtering
      the hundreds of variants on WES from an individual's DNA selected by the
      phenotype. We investigated a patient with a slowly progressive chronic axonal
      distal motor neuropathy and extrapyramidal syndrome using WES, in whom common
      genetic mutations had been excluded. Variant filtering identified potentially
      deleterious mutations in three known disease genes: DCTN1, KIF5A and NEFH, which
      have been all associated with similar clinical presentations of amyotrophic
      lateral sclerosis, Parkinsonism and/or hereditary spastic paraplegia. Predicting
      the functional effect of the mutations were analysed in parallel with detailed
      clinical investigations. This case highlights the difficulties and pitfalls of
      applying WES in patients with complex neurological diseases and serves as an
      instructive tale. 

PMID- 25957633
TI  - Acute optic neuropathy associated with a novel MFN2 mutation.
AB  - Mutations in the mitofusin 2 (MFN2) gene cause CMT2A the most common form of
      autosomal dominant axonal Charcot-Marie-Tooth (CMT). In addition, mutations in
      MFN2 have been shown to be responsible for Hereditary Motor Sensory Neuropathy
      type VI (HSMN VI), a rare early-onset axonal CMT associated with optic
      neuropathy. Most reports of HMSN VI presented with a sub-acute form of optic
      neuropathy. Herein, we report a CMT2A patient, who developed very rapidly
      progressing severe optic neuropathy. A 40-year-old Caucasian man was evaluated
      for gait disturbance and lower limbs weakness, slowly progressed over the last 2
      years. Due to clinical data and family history, a diagnosis of CMT2 was made. The
      novel heterozygous c.775C > T (p.Arg259Cys) mutation in MFN2 was detected in the
      patient and his clinical affected mother. Interestingly, the patient developed a
      severe sudden bilateral visual deterioration few years early, with clinical and
      instrumental picture suggestive of acute bilateral optic neuropathy. Our report
      expands the spectrum of MFN2-related manifestation because it indicates that
      visual symptoms of HMSN VI may enter in the differential with acquired or
      hereditary acute optic neuropathies, and that severe optic neuropathy is not
      invariably an early manifestation of the disease but may occur as disease
      progressed. This report could have an impact on clinicians who evaluate patients
      with otherwise unexplainable bilateral acute-onset optic neuropathy, especially
      if associated with a motor and sensory axonal neuropathy. 

PMID- 25957630
TI  - A novel closed-body model of spinal cord injury caused by high-pressure air
      blasts produces extensive axonal injury and motor impairments.
AB  - Diffuse axonal injury is thought to be the basis of the functional impairments
      stemming from mild traumatic brain injury. To examine how axons are damaged by
      traumatic events, such as motor vehicle accidents, falls, sports activities, or
      explosive blasts, we have taken advantage of the spinal cord with its extensive
      white matter tracts. We developed a closed-body model of spinal cord injury in
      mice whereby high-pressure air blasts targeted to lower thoracic vertebral levels
      produce tensile, compressive, and shear forces within the parenchyma of the
      spinal cord and thereby cause extensive axonal injury. Markers of cytoskeletal
      integrity showed that spinal cord axons exhibited three distinct pathologies:
      microtubule breakage, neurofilament compaction, and calpain-mediated spectrin
      breakdown. The dorsally situated axons of the corticospinal tract primarily
      exhibited microtubule breakage, whereas all three pathologies were common in the
      lateral and ventral white matter. Individual axons typically demonstrated only
      one of the three pathologies during the first 24h after blast injury, suggesting
      that the different perturbations are initiated independently of one another. For
      the first few days after blast, neurofilament compaction was frequently
      accompanied by autophagy, and subsequent to that, by the fragmentation of
      degenerating axons. TuJ1 immunolabeling and mice with YFP-reporter labeling each
      revealed more extensive microtubule breakage than did betaAPP immunolabeling,
      raising doubts about the sensitivity of this standard approach for assessing
      axonal injury. Although motor deficits were mild and largely transient, some
      aspects of motor function gradually worsened over several weeks, suggesting that
      a low level of axonal degeneration continued past the initial wave. Our model can
      help provide further insight into how to intervene in the processes by which
      initial axonal damage culminates in axonal degeneration, to improve outcomes
      after traumatic injury. Importantly, our findings of extensive axonal injury also
      caution that repeated trauma is likely to have cumulative adverse consequences
      for both brain and spinal cord. 

PMID- 25957634
TI  - Centronuclear myopathies: genotype-phenotype correlation and frequency of defined
      genetic forms in an Italian cohort.
AB  - Centronuclear myopathies (CNMs) are a group of clinically and genetically
      heterogeneous muscle disorders. To date, mutation in 7 different genes has been
      reported to cause CNMs but 30 % of cases still remain genetically undefined.
      Genetic investigations are often expensive and time consuming. Clinical and
      morphological clues are needed to facilitate genetic tests and to choose the best
      approach for genetic screening. We aimed to describe genotype-phenotype
      correlation in an Italian cohort of patients affected by CNMs, to define the
      relative frequencies of its defined genetic forms and to draw a diagnostic
      algorithm to address genetic investigations. We recruited patients with CNMs from
      all the Italian tertiary neuromuscular centers following clinical and
      histological criteria. All selected patients were screened for the four
      'canonical' genes related to CNMs: MTM1, DNM2, RYR1 and BIN1. Pathogenetic
      mutations were found in 38 of the 54 screened patients (70 %), mostly in patients
      with congenital onset (25 of 30 patients, 83 %): 15 in MTM1, 6 in DNM2, 3 in RYR1
      and one in TTN. Among the 13 patients with a childhood-adolescence onset,
      mutations were found in 6 patients (46 %), all in DNM2. In the group of the 11
      patients with adult onset, mutations were identified in 7 patients (63 %), again
      in DNM2, confirming that variants in this gene are relatively more common in late
      onset phenotypes. The present study provides the relative molecular frequency of
      centronuclear myopathy and of its genetically defined forms in Italy and also
      proposes a diagnostic algorithm to be used in clinical practice to address
      genetic investigations. 

PMID- 25957636
TI  - Executive dysfunction predicts social cognition impairment in amyotrophic lateral
      sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of the motor
      system with recognised extra-motor and cognitive involvement. This cross
      sectional study examined ALS patients' performance on measures requiring social
      inference, and determined the relationship between such changes and variations in
      mood, behaviour, personality, empathy and executive function. Fifty-five ALS
      patients and 49 healthy controls were compared on tasks measuring social
      cognition and executive function. ALS patients also completed measures examining
      mood, behaviour and personality. Regression analyses explored the contribution of
      executive function, mood, behaviour and personality to social cognition scores
      within the ALS sample. A between-group MANOVA revealed that, the ALS group was
      impaired relative to controls on two composite scores for social cognition and
      executive function. Patients also performed worse on individual tests of
      executive function measuring cognitive flexibility, response inhibition and
      concept formation, and on individual aspects of social cognition assessing the
      attribution of emotional and mental states. Regression analyses indicated that
      ALS-related executive dysfunction was the main predictor of social cognition
      performance, above and beyond demographic variables, behaviour, mood and
      personality. On at least some aspects of social cognition, impaired performance
      in ALS appears to be secondary to executive dysfunction. The profile of cognitive
      impairment in ALS supports a cognitive continuum between ALS and frontotemporal
      dementia. 

PMID- 25957635
TI  - Review of delirium in patients with Parkinson's disease.
AB  - Parkinson's disease (PD) is common and has a number of associated
      neuropsychiatric disturbances. Of these, delirium has historically been under
      recognised. Delirium is an acute disturbance of attention and awareness that
      fluctuates, and is accompanied by an additional disturbance of cognition. As
      delirium is known to carry a particularly poor prognosis in terms of morbidity
      and mortality, and the relationship between delirium and dementia is becoming
      better defined, we completed a literature review of delirium in the context of
      PD. A literature search was completed using the databases PubMed, Embase and Ovid
      Medline. PubMed (1945-2014) was searched in September 2014; Embase (1974-2014);
      and Ovid Medline (1946-2014) in October 2014. The search terms 'delirium' and
      'Parkinsons' in combination were used. Large studies using a robust definition of
      delirium were lacking in PD. There is the suggestion that PD is a risk factor for
      delirium and that delirium negatively impacts upon the motor symptom trajectory.
      Deficits in the neurotransmitters dopamine and acetylcholine are implicated in
      the pathophysiology of delirium in PD. Systemic inflammation also appears to have
      a role. Treatment of delirium in PD should include medication review and cautious
      use of atypical antipsychotics where pharmacological treatment is indicated. Of
      the atypical antipsychotics studied, quetiapine has the least extrapyramidal side
      effects. Evidence suggests a specific link between delirium and PD but well
      designed clinical studies to evaluate the prevalence, impact and treatment of
      delirium in PD are required. Given the potential to improve outcomes through
      delirium prevention we conclude that delirium in PD is an area worthy of further
      study. 

PMID- 25957637
TI  - Clinical variability in ataxia-telangiectasia.
AB  - Ataxia-telangiectasia (A-T) is an autosomal recessive inherited disease
      characterized by progressive childhood-onset cerebellar ataxia, oculomotor
      apraxia, choreoathetosis and telangiectasias of the conjunctivae. Further
      symptoms may be immunodeficiency and frequent infections, and an increased risk
      of malignancy. As well as this classic manifestation, several other non-classic
      forms exist, including milder or incomplete A-T phenotypes caused by homozygous
      or compound heterozygous mutations in the ATM gene. Recently, ATM mutations have
      been found in 13 Canadian Mennonites with early-onset, isolated, predominantly
      cervical dystonia, in a French family with generalized dystonia and in an Indian
      family with dopa-responsive cervical dystonia. In this article, we will describe
      a Turkish family with three affected sibs. Their phenotypes range from pure
      cervical dystonia associated with hand tremor to truncal and more generalized
      dystonic postures. Exome sequencing has revealed the potentially pathogenic
      compound heterozygous variants p.V2716A and p.G301VfsX19 in the ATM gene. The
      variants segregated perfectly with the phenotypes within the family. Both
      mutations detected in ATM have been shown to be pathogenic, and the alpha
      fetoprotein, a marker of ataxia telangiectasia, was found to be increased. This
      report supports recent literature showing that ATM mutations are not exclusively
      associated with A-T but may also cause a more, even intra-familial variable
      phenotype in particular in association with dystonia. 

PMID- 25957639
TI  - Walking function in clinical monitoring of multiple sclerosis by telemedicine.
AB  - Walking limitation is a key component of disability in patients with multiple
      sclerosis (MS), but the information on daily walking activity and disability over
      time is limited. To determine, (1) the agreement between the standard
      measurements of MS-related disability [expanded disability status scale (EDSS),
      functional systems (FS) and ambulation index (AI)] obtained by conventional and
      remote evaluation using a multimedia platform; (2) the usefulness of monitoring 6
      min walk test (6MWT) and average daily walking activity (aDWA) to better
      characterize patients disability. Twenty-five patients (EDSS score 1.0-6.5) were
      evaluated every 3 months for the first year, and aDWA repeated at year 2. Remote
      visits included the recording of a video with self-performed neurological
      examination and specific multimedia questionnaires. aDWA was measured by a
      triaxial accelerometer. All but two patients completed the study. Modest
      agreement between conventional and multimedia EDSS was found for EDSS <= 4.0
      (kappa = 0.2) and good for EDSS >= 4.5 (kappa = 0.6). For the overall sample,
      pyramidal, cerebellar and brainstem FS showed the greatest agreement (kappa =
      0.7). SR-AI showed a modest agreement for EDSS <= 4.0 and good for EDSS >= 4.5
      (kappa = 0.3 and 0.6, respectively). There was a strong correlation between
      conventional and 6MWT measured by accelerometer (r = 0.76). The aDWA correlated
      strongly with the EDSS (r = -0.86) and a cut-off point of 3279.3 steps/day
      discriminated patients with ambulatory impairment. There was a significant
      decline in aDWA over 2 years in patients with ambulatory impairment that were not
      observed by standard measurements of disability. MS clinical monitoring by
      telemedicine is feasible, but the observed lower agreement in less disabled
      patients emphasizes the need to optimize the assessment methodology.
      Accelerometers capture changes that may indicate deterioration over time.

PMID- 25957640
TI  - Very late-onset neuromyelitis optica spectrum disorder beyond the age of 75.
AB  - Aquaporin-4 antibody (AQP4-Ab)-positive neuromyelitis optica spectrum disorder
      (NMOSD) is a rare but often severe autoimmune disease with median onset around 40
      years of age. We report characteristics of three very-late-onset NMOSD (including
      complete NMO) patients >75 years of age, in whom this diagnosis initially seemed
      unlikely because of their age and age-associated concomitant diseases, and
      briefly review the literature. All three patients, aged 79, 82 and 88 years,
      presented with a spinal cord syndrome as the first clinical manifestation of AQP4
      Ab-positive NMOSD. They all had severe relapses unless immunosuppressive therapy
      was initiated, and one untreated patient died of a fatal NMOSD course. Two
      patients developed side effects of immunosuppression. We conclude that a first
      manifestation of NMOSD should be considered even in patients beyond the age of 75
      years with a compatible syndrome, especially longitudinally extensive myelitis.
      Early diagnosis and treatment are feasible and highly relevant. Special attention
      is warranted in the elderly to recognize adverse effects of immunosuppressive
      therapies as early as possible.

PMID- 25957638
TI  - Cognitive impairment and memory disorders in relapsing-remitting multiple
      sclerosis: the role of white matter, gray matter and hippocampus.
AB  - Cognitive disorders occur in up to 65 % of multiple sclerosis (MS) patients; they
      have been correlated with different MRI measures of brain tissue damage, whole
      and regional brain atrophy. The hippocampal involvement has been poorly
      investigated in cognitively impaired (CI) MS patients. The objective of this
      study is to analyze and compare brain tissue abnormalities, including hippocampal
      atrophy, in relapsing-remitting MS (RRMS) patients with and without cognitive
      deficits, and to investigate their role in determining cognitive impairment in
      MS. Forty-six RRMS patients [20 CI and 26 cognitively preserved (CP)] and 25 age,
      sex and education-matched healthy controls (HCs) underwent neuropsychological
      evaluation and 3-Tesla anatomical MRI. T2 lesion load (T2-LL) was computed with a
      semiautomatic method, gray matter volume and white matter volume were estimated
      using SIENAX. Hippocampal volume (HV) was obtained by manual segmentation. Brain
      tissues volumes were compared among groups and correlated with cognitive
      performances. Compared to HCs, RRMS patients had significant atrophy of WM, GM,
      left and right Hippocampus (p < 0.001). Compared to CP, CI RRMS patients showed
      higher T2-LL (p = 0.02) and WM atrophy (p = 0.01). In the whole RRMS group,
      several cognitive tests correlated with brain tissue abnormalities (T2-LL, WM and
      GM atrophy); only verbal memory performances correlated with left hippocampal
      atrophy. Our results emphasize the role of T2-LL and WM atrophy in determining
      clinically evident cognitive impairment in MS patients and provide evidence that
      GM and hippocampal atrophy occur in MS patients regardless of cognitive status.

PMID- 25957641
TI  - Associations between co-medications and survival in ALS-a cohort study from
      Austria.
AB  - The aim of this study was to evaluate associations between co-medications and
      survival of patients with amyotrophic lateral sclerosis (ALS). Prescription
      databases of the Austrian sickness funds covering more than 5 million people
      formed the basis of this study. ALS cases were deduced from riluzole
      prescriptions during the study period from January 1, 2008, to June 30, 2012.
      After adjusting for potential confounding factors associations between co
      medications and ALS survival were analyzed. A total of 522 ALS patients could be
      identified during the study period. Sixteen of the most frequently used drug
      classes were considered for the survival analyses of which two were nominally
      associated with ALS survival. Proton pump inhibitors (PPI) were negatively
      correlated with survival (HR 1.34, 95 % CI 1.04-1.73) and centrally acting muscle
      relaxants (CAMR) showed a positive association (HR 0.56, 95 % CI 0.39-0.81).
      After correcting for multiple testing, the association between CAMR and ALS
      survival remained significant (p = 0.03). In conclusion, this is the first study
      systematically evaluating potential associations between commonly used drugs and
      ALS disease course. We report a positive association between CAMR use and
      survival, which may have derived from an indication bias representing the better
      prognosis of the upper motor neuron predominant disease variant. However, this is
      still interesting since it demonstrates the sensitivity of our study design to
      pick up survival effects. The use of large prescription registries could thus
      provide a valuable basis to find clues to underlying pathophysiological
      mechanisms in ALS. 

PMID- 25957642
TI  - A novel HTRA1 exon 2 mutation causes loss of protease activity in a Pakistani
      CARASIL patient.

PMID- 25957643
TI  - Neuroimaging in diagnosis of atypical polyradiculoneuropathies: report of three
      cases and review of the literature.
AB  - Neuroimaging is increasingly used in the study of peripheral nerve diseases, and
      sometimes may have a pivotal role in the diagnostic process. We report on three
      patients with atypical chronic inflammatory polyradiculoneuropathy (CIDP) in whom
      magnetic resonance imaging (MRI) and nerve Ultrasound (US) were crucial for a
      correct diagnostic work-out. A literature review on MRI and US in acquired
      demyelinating polyneuropathies is also provided. Awareness of the imaging
      features of CIDP will assist in confirmation of the diagnosis, institution of the
      appropriate therapy, and prevention of inadequate or delayed treatment in
      atypical CIDP. 

PMID- 25957644
TI  - Clinical and electroencephalographic on-off effect of amantadine in chronic non
      traumatic minimally conscious state.

PMID- 25957645
TI  - Resistance to wheat yellow mosaic virus in Madsen wheat is controlled by two
      major complementary QTLs.
AB  - KEY MESSAGE: Wheat yellow mosaic virus resistance of Madsen is governed by two
      complementary QTLs, Qym1 and Qym2 , located on chromosome arms 2DL and 3BS. Wheat
      yellow mosaic, caused by Wheat yellow mosaic virus (WYMV), is one of the most
      serious wheat diseases in East Asia. In this study, recombinant inbred lines
      (RILs, F9) from a cross between cultivars Madsen (resistant) and Hokushin
      (susceptible) grown in a WYMV-infected nursery field were tested for the presence
      of WYMV in leaves by enzyme-linked immunosorbent assay (ELISA) and genotyped by
      using genome-wide molecular markers. Two major QTLs were detected: Qym1 located
      between Xgwm539 and Xgwm349 on chromosome 2DL and Qym2 located between Xbarc147
      and Xwmc623 on chromosome 3BS. The resistance alleles for both QTLs originated
      from Madsen. The third QTL Qym3 located near Xwmc457 on chromosome 4D, where the
      resistant allele for this QTL originated from Hokushin. Although the Qym3 was
      rather minor, it was essential to complement Qym1 and Qym2 for complete avoidance
      of WYMV infection. Near-isogenic lines carrying the resistance QTLs were
      developed by repeated backcrosses using Madsen as the donor parent and Hokushin
      as the recurrent parent. The lines that were resistant to WYMV (as tested by
      ELISA) were homozygous for the Madsen alleles at both Qym1 and Qym2. Qym1
      dominance was partial, whereas that of Qym2 was nearly complete. Qym1 was closely
      linked to Xwmc41; Qym2 was closely linked to Xwmc754. These markers will be
      useful in marker-assisted selection in wheat breeding for WYMV resistance; this
      study will facilitate cloning the WYMV resistance genes.

PMID- 25957646
TI  - Comparative fine mapping of the Wax 1 (W1) locus in hexaploid wheat.
AB  - KEY MESSAGE: By applying comparative genomics analyses, a high-density genetic
      linkage map of the Wax 1 ( W1 ) locus was constructed as a framework for map
      based cloning. Glaucousness is described as the scattering effect of visible
      light from wax deposited on the cuticle of plant aerial organs. In wheat, the wax
      on leaves and stems is mainly controlled by two sets of genes: glaucousness loci
      (W1 and W2) and non-glaucousness loci (Iw1 and Iw2). Bulked segregant analysis
      (BSA) and simple sequence repeat (SSR) mapping showed that Wax1 (W1) is located
      on chromosome arm 2BS between markers Xgwm210 and Xbarc35. By applying
      comparative genomics analyses, colinearity genomic regions of the W1 locus on
      wheat 2BS were identified in Brachypodium distachyon chromosome 5, rice
      chromosome 4 and sorghum chromosome 6, respectively. Four STS markers were
      developed using the Triticum aestivum cv. Chinese Spring 454 contig sequences and
      the International Wheat Genome Sequencing Consortium (IWGSC) survey sequences. W1
      was mapped into a 0.93 cM genetic interval flanked by markers XWGGC3197 and
      XWGGC2484, which has synteny with genomic regions of 56.5 kb in Brachypodium, 390
      kb in rice and 31.8 kb in sorghum. The fine genetic map can serve as a framework
      for chromosome landing, physical mapping and map-based cloning of the W1 in
      wheat.

PMID- 25957648
TI  - Neuropsychological investigations in obsessive-compulsive disorder: A systematic
      review of methodological challenges.
AB  - The inconsistent nature of the neuropsychology literature pertaining to obsessive
      compulsive disorder (OCD) has long been recognized. However, individual studies,
      systematic reviews, and recent meta-analytic reviews were unsuccessful in
      establishing a consensus regarding a disorder-specific neuropsychological
      profile. In an attempt to identify methodological factors that may contribute to
      the inconsistency that is characteristic of this body of research, a systematic
      review of methodological factors in studies comparing OCD patients and non
      psychiatric controls on neuropsychological tests was conducted. This review
      covered 115 studies that included nearly 3500 patients. Results revealed a range
      of methodological weaknesses. Some of these weaknesses have been previously noted
      in the broader neuropsychological literature, while some are more specific to
      psychiatric disorders, and to OCD. These methodological shortcomings have the
      potential to hinder the identification of a specific neuropsychological profile
      associated with OCD as well as to obscure the association between neurocognitive
      dysfunctions and contemporary neurobiological models. Rectifying these weaknesses
      may facilitate replicability, and promote our ability to extract cogent,
      meaningful, and more unified inferences regarding the neuropsychology of OCD. To
      that end, we present a set of methodological recommendations to facilitate future
      neuropsychology research in psychiatric disorders in general, and in OCD in
      particular. 

PMID- 25957647
TI  - Gene expression profiles of FABP genes in protochordates, Ciona intestinalis and
      Branchiostoma belcheri.
AB  - Fatty-acid-binding proteins (FABPs) are small intracellular proteins associated
      with the transportation of fatty acids. Members of the FABPs share similar amino
      acid sequences and tertiary structures and form, together with a member of the
      cellular retinol-binding proteins (CRBPs), the intracellular-lipid-binding
      protein (iLBP) family. In vertebrates, several types of FABP have been isolated
      and classified into three subfamilies: 2-4. In invertebrates, several FABP
      related proteins have been reported in protostomes and amphioxus; however, little
      is known about the relationship between their phylogenetic positions and
      expression patterns. We have performed a genome-wide survey of FABP-related genes
      in protochordates: amphioxus Branchiostoma belcheri and the ascidian Ciona
      intestinalis. Comprehensive BLAST searches in NCBI and the Ciona Ghost Database
      by using amino acid sequences of all FABPs have revealed that the ascidian C.
      intestinalis and amphioxus B. belcheri contain six and seven FABP-related genes
      in their haploid genomes, respectively. Expression pattern analyses by whole
      mount in situ hybridization in Ciona transparent juveniles and serial-section in
      situ hybridizations in adult amphioxus have revealed that all genes are mainly
      expressed in the postpharyngeal digestive tract. In particular, the expression of
      FABP-related genes of subfamily-2 (liver/ileum type) and subfamily-3 (intestinal
      type) in the ascidian pyloric gland and amphioxus hepatic cecum provides insight
      into the evolution of hepatic-related structures of chordates and FABP-related
      genes. 

PMID- 25957649
TI  - Revisiting attentional processing of non-emotional cues in social anxiety: A
      specific impairment for the orienting network of attention.
AB  - People with social anxiety disorder (SAD) exhibit an attentional bias for threat
      (AB). Nevertheless, the focus on AB for emotional stimuli has led to neglect the
      exploration of basic attention deficits for non-emotional material among SAD
      patients. This study aimed to investigate the integrity of the attentional system
      in SAD. The Attention Network Test was used to precisely explore attentional
      deficits, and centrally the differential deficit across the three attentional
      networks, namely alerting (allowing to achieve and maintain a state of
      alertness), orienting (allowing to select information from sensory input by
      engaging or disengaging attention to one stimulus among others and/or shifting
      the attentional resources from one stimulation to another), and executive control
      (involving the top-down control of attention and allowing to resolve response
      conflicts). Twenty-five patients with SAD were compared to 25 matched controls.
      SAD patients exhibited a specific impairment for the orienting network (p <
      0.001) but preserved performance for the alerting and executive networks.
      Complementary analyses revealed that this impairment may result from a faster
      attentional engagement to task-irrelevant material. The orienting impairment was
      highly correlated with the intensity of the social anxiety symptoms, but did not
      correlate either with trait-anxiety, state-anxiety, or depressive symptoms.

PMID- 25957650
TI  - The use of the Gait Deviation Index for the evaluation of participants following
      total hip arthroplasty: An explorative randomized trial.
AB  - INTRODUCTION: In this paper, the Gait Deviation Index (GDI) was used as a
      convenient method to evaluate pre-to-postoperative gait pattern changes after
      total hip arthroplasty and identify factors which might be predictive of outcome.
      DESIGN: Three-dimensional gait data from a randomized clinical trial was used to
      determine changes in gait quality in participants walking at self-selected speed.
      Upon completion of the first assessment, the participants were randomly assigned
      to either resurfacing hip arthroplasty or conventional hip arthroplasty. The
      outcome was changes in overall gait 'quality' measured with GDI during the 6
      month post-surgery follow-up period. RESULTS: 38 participants with severe
      unilateral primary hip osteoarthritis took part in the trial. We found no
      difference in change scores between the two treatment groups; 1.9 [95%CI: -0.3 to
      4.0] or between change scores for the non-operated and the operated limbs; 0.3
      [95%CI: -2.3 to 1.7]. However, the score for the two groups (pooled data)
      improved after surgery by 4.4 [95%CI: 1.8-7.0]. The single level regression
      analysis identified the preoperative GDI score as a strong predictor of outcome
      (p<0.001). CONCLUSION: Six months after surgery, there was no additional effect
      of resurfacing hip arthroplasty on GDI scores compared with conventional hip
      arthroplasty. Participants with the most pathological preoperative gait pattern
      improved the most. The GDI increased, which indicates an overall improvement in
      gait pathology after surgery. TRIAL REGISTRATION: NCT01229293.

PMID- 25957651
TI  - Generalised cognitive motor interference in multiple sclerosis.
AB  - Researchers have examined cognitive motor interference (CMI) for lower extremity
      function in MS, but have not examined this in the upper extremity. This study
      examined CMI for both lower and upper extremity motor tasks in persons with MS
      and without MS. Eighty-two persons walked on a GAITRite electronic walkway
      (velocity) and performed the nine-hole peg test (NHPT, seconds) without (single
      task) and with a cognitive challenge (dual task). The data were analysed with
      mixed-factor ANOVA and Pearson correlations. When comparing MS and controls,
      there were statistical significant and exceptionally large Task main effects on
      gait velocity (etap(2)=.41; F1,60=55.78; p<.005) and NHPT performance
      (etap(2)=.62; F1,60=127.8; p<.005). When considering disability status among
      those with MS, there were statistically significant and large Task main effects
      on velocity (etap(2)=.38; F1,60=37.3; p<.005) and NHPT test (etap(2)=.62;
      F1,60=95.7; p<.005). The dual task cost of walking and performing the NHPT were
      significantly correlated in the entire sample, those with MS and controls, and in
      those with MS who had mild, moderate, and severe disability (all |r|>.450). CMI
      occurs in both the lower and upper extremities, and is comparable between persons
      with and without MS and across MS disability level. 

PMID- 25957652
TI  - Consistent accuracy in whole-body joint kinetics during gait using wearable
      inertial motion sensors and in-shoe pressure sensors.
AB  - To analyze human motion such as daily activities or sports outside of the
      laboratory, wearable motion analysis systems have been recently developed. In
      this study, the joint forces and moments in whole-body joints during gait were
      evaluated using a wearable motion analysis system consisting of an inertial
      motion measurement system and an in-shoe pressure sensor system. The magnitudes
      of the joint forces and the moments in nine joints (cervical, thoracic, lumbar,
      right shoulder, right elbow, right wrist, right hip, right knee, and right ankle)
      during gait were calculated using the wearable system and the conventional
      system, respectively, based on a standard inverse dynamics analysis. The averaged
      magnitudes of the joint forces and moments of five subjects were compared between
      the wearable and conventional systems in terms of the Pearson's correlation
      coefficient and the normalized root mean squared error to the maximum value from
      the conventional system. The results indicated that both the joint forces and
      joint moments in human whole body joints using wearable inertial motion sensors
      and in-shoe pressure sensors were feasible for normal motions with a low speed
      such as walking, although the lower extremity joints showed the strongest
      correlation and overall the joint moments were associated with relatively smaller
      correlation coefficients and larger normalized root mean squared errors in
      comparison with the joint forces. The portability and mobility of this wearable
      system can provide wide applicability in both clinical and sports motion
      analyses. 

PMID- 25957653
TI  - The archaeology, chronology and stratigraphy of Madjedbebe (Malakunanja II): A
      site in northern Australia with early occupation.
AB  - Published ages of >50 ka for occupation at Madjedbebe (Malakunanja II) in
      Australia's north have kept the site prominent in discussions about the
      colonisation of Sahul. The site also contains one of the largest stone artefact
      assemblages in Sahul for this early period. However, the stone artefacts and
      other important archaeological components of the site have never been described
      in detail, leading to persistent doubts about its stratigraphic integrity. We
      report on our analysis of the stone artefacts and faunal and other materials
      recovered during the 1989 excavations, as well as the stratigraphy and
      depositional history recorded by the original excavators. We demonstrate that the
      technology and raw materials of the early assemblage are distinctive from those
      in the overlying layers. Silcrete and quartzite artefacts are common in the early
      assemblage, which also includes edge-ground axe fragments and ground haematite.
      The lower flaked stone assemblage is distinctive, comprising a mix of long
      convergent flakes, some radial flakes with faceted platforms, and many small thin
      silcrete flakes that we interpret as thinning flakes. Residue and use-wear
      analysis indicate occasional grinding of haematite and woodworking, as well as
      frequent abrading of platform edges on thinning flakes. We conclude that previous
      claims of extensive displacement of artefacts and post-depositional disturbance
      may have been overstated. The stone artefacts and stratigraphic details support
      previous claims for human occupation 50-60 ka and show that human occupation
      during this time differed from later periods. We discuss the implications of
      these new data for understanding the first human colonisation of Sahul.

PMID- 25957654
TI  - Isotopic evidence for Last Glacial climatic impacts on Neanderthal gazelle
      hunting territories at Amud Cave, Israel.
AB  - The Middle Paleolithic site of Amud Cave, Israel, was occupied by Neanderthals at
      two different time periods, evidenced by two chronologically and
      stratigraphically distinct depositional sub-units (B4 and B2/B1) during MIS 4 and
      MIS 3, respectively. The composition of both hunted large fauna and naturally
      deposited micromammalian taxa is stable at the site over time, despite a ~ 10 ky
      gap between the two occupation phases. However, while gazelle is the most
      ubiquitous hunted species throughout the occupation, isotopic analysis showed
      that there is a marked change in Neanderthal hunting ranges between the early
      (B4) and late (B2/B1) phases. Hunting ranges were reconstructed by comparing
      oxygen, carbon, and strontium isotopes from gazelle tooth enamel with modern
      isotope data from the Amud Cave region. This region is characterized by extensive
      topographic, lithological, and pedological heterogeneity. During the early
      occupation phase negative oxygen isotope values, low radiogenic (87)Sr/(86)Sr
      ratios, and low Sr concentrations reveal restricted gazelle hunting in the high
      elevations west of Amud Cave. In the late occupation phase, hunting ranges became
      more diverse, but concentrate at low elevations closer to the site. Climatic
      proxies indicate that conditions were drier in the early occupation phase, which
      may have pushed gazelle populations into higher, more productive foraging areas.
      This study showed that Neanderthals adjusted their hunting territories
      considerably in relation to varying environmental conditions over the course of
      occupation in Amud Cave. It highlights the utility of multiple isotope analysis
      in enhancing the resolution of behavioral interpretations based on faunal remains
      and in reconstructing past hunting behaviors of Paleolithic hominins.

PMID- 25957656
TI  - C-type lectin domain family 12, member A: A common denominator in Behcet's
      syndrome and acute gouty arthritis.
AB  - C-type lectin domain family 12, member A (CLEC12A) is a C-type lectin-like
      pattern recognition receptor capable of recognizing monosodium urate crystals.
      Monosodium urate crystals, the causative agents of gout are also among the danger
      associated molecular patterns reflecting cellular injury/cell death. In response
      to monosodium urate crystals, CLEC12A effectively inhibits granulocyte and
      monocyte/macrophage functions and hence acts as a negative regulator of
      inflammation. Behcet's syndrome and gout are autoinflammatory disorders sharing
      certain pathological (neutrophilic inflammation), clinical (exaggerated response
      to monosodium urate crystals) and therapeutic (colchicine) features. We propose
      the hypothesis that decreased expression of CLEC12A is a common denominator in
      the hyperinflammatory responses observed in Behcet's syndrome and gout. Major
      lines of evidence supporting this hypothesis are: (1) Downregulation/deficiency
      of CLEC12A is associated with hyperinflammatory responses. (2) CLEC12A
      polymorphisms with functional and clinical implications have been documented in
      other inflammatory diseases. (3) Colchicine, a fundamental therapeutic agent used
      both in Behcet's syndrome and gout is shown to oppose the downregulation of
      CLEC12A. (4) Behcet's syndrome and gout are characterized by a hyperinflammatory
      response to monosodium urate crystals and other than gout, Behcet's syndrome is
      the only inflammatory condition exhibiting this exaggerated response. (5)
      Genomewide linkage and association studies of Behcet's syndrome collectively
      point to 12p12-13, the chromosomal region harboring CLEC12A. (6) Patients with
      severe forms of Behcet's syndrome underexpress CLEC12A with respect to patients
      with mild forms of the disease. If supported by well-designed, rigorous
      experiments, the forementioned hypothesis pertinent to CLEC12A will carry
      important implications for therapy, designing experimental models, and uncovering
      immunopathogenic mechanisms in Behcet's syndrome and gout. 

PMID- 25957655
TI  - Role of medial abrasion phenomenon in the pathogenesis of knee osteoarthritis.
AB  - Osteoarthritis of the knee affects a large population worldwide and is associated
      with an extremely high economic burden largely attributable to the effects of
      disability, comorbid disease, and the expense of treatment. Since the initiating
      events that result in the cartilage degradation are poorly understood, there has
      been very limited success in demonstrating disease modification in clinical
      trials of potential therapies. Medial plica related medial abrasion phenomenon
      has recently been identified to have close relationship with medial compartment
      osteoarthritis. We hypothesized that this abrasion phenomenon will elicit
      lifelong interplay between pathologic medial plica and the facing medial femoral
      condyle and might play a role in the pathogenesis of knee osteoarthritis by both
      physical and chemical effects. After evaluating current evidence, we designed a
      study to prove that the concentrations of total protein, cartilage degrading
      related cytokines (tumor necrosis factor-alpha and interleukin-1beta) and enzyme
      (matrix metalloproteinase-3) are higher in the medial compartment of the knee
      having the phenomenon of medial abrasion. The accumulating data and findings
      about medial abrasion phenomenon might be important for the understanding of the
      pathogenesis or progression of this common disease. We hope that our hypothesis
      will stimulate further studies verifying if medial abrasion phenomenon plays more
      roles in the pathogenesis of knee osteoarthritis. Further clinical observations
      for its appropriate treatment based on this hypothesis are also mandatory for the
      benefits of patients. 

PMID- 25957657
TI  - The bond force constant and bulk modulus of small fullerenes using density
      functional theory and finite element analysis.
AB  - Dedicated bond force constant and bulk modulus of C n fullerenes (n = 20, 28, 36,
      50, 60) are computed using density functional theory (DFT). DFT predicts bond
      force constants of 611, 648, 675, 686, and 691 N/m, for C20, C28, C36, C50, and
      C60, respectively, indicating that the bond force constant increases for larger
      fullerenes. The bulk modulus predicted by DFT increases with decreased fullerene
      diameter, from 0.874 TPa for C60 to 1.830 TPa for C20. The bond force constants
      predicted by DFT are then used as an input for finite element analysis (FEA) of
      the fullerenes, considered as spatial frames in structural models where the bond
      stiffness is represented by the DFT-computed bond force constant. In agreement
      with DFT, FEA predicts that smaller fullerenes are stiffer, and underestimates
      the bulk modulus with respect to DFT. The difference between the FEA and DFT
      predictions of the bulk modulus decreases as the size of the fullerene increases,
      from 20.9% difference for C20 to only 4% difference for C60. Thus, it is
      concluded that knowing the appropriate bond force constant, FEA can be used as a
      plausible approximation to model the elastic behavior of small fullerenes.

PMID- 25957659
TI  - Computational simulation study on the anion recognition properties of
      functionalized tetraphenyl porphyrins.
AB  - The anion recognitions of tetra-(2-formamido) phenyl porphyrin (APP), tetra-(2
      ureido) phenyl porphyrin (UPP), and their zinc derivatives (ZnAPP and ZnUPP) to
      three anions (Cl(-), H2PO4 (-), CH3COO(-)) were studied using quantum mechanical
      calculations (QM) and molecular dynamics (MD) simulations. The density functional
      theory (DFT) calculations at M06-2X/6-31G (d, p) level indicated that the anion
      recognition ability of ZnAPP was better than that of APP, and the anion
      selectivity was in the order Cl(-) < H2PO4 (-) < CH3COO(-). The selectivity
      trends for ZnUPP and UPP were found to be H2PO4 (-) < Cl(-) < CH3COO(-). The
      structures, thermodynamic properties, and recognition mechanisms were discussed
      in detail. The 2 ns MD simulations were then carried out for anion@ZnAPP and
      anion@ZnUPP complexes in mixed solvent DMSO/water. The MD simulation results
      showed that anion@ZnUPP complexes exhibited higher stability than anion@ZnAPP,
      which was in good agreement with QM results. H-bonds formed between the anions
      and the side-chains of receptors, and zinc coordination bonds with anions
      contributed significantly to the stability of complexes. The anion selectivity of
      ZnAPP and ZnUPP in the solvent phase were also discussed and compared with those
      in the gas phase. 

PMID- 25957660
TI  - 2'-Hydroxyflavanone: A promising molecule for kidney cancer prevention.
AB  - Kidney cancer, also known as renal cell carcinoma (RCC), is one of the top 10
      diagnosed cancers in the USA, and the incidence is rising. Despite major
      improvements in drug therapy strategies, RCC remains a deadly malignancy if not
      found and removed in its early stages. RCC is so highly drug-resistant that no
      effective life-prolonging regimen of cytotoxic chemotherapy has been demonstrated
      for RCC, despite several decades of effort. It is also highly radiation
      resistant, thus circumventing therapies to prevent local recurrence or to control
      metastatic disease. In the last few years, extensive research has been conducted
      to elucidate the functional significance of the plant-derived compounds, and
      their derivatives, as anticancer agents. This review is focussed on a chemo
      dietary prevention strategy against RCC using a citrus-derived compound called 2'
      hydroxyflavanone. RCC is frequently caused by VHL gene mutations, which
      contribute to 75% of all RCCs. These mutations are positively linked to cigarette
      smoking, and exposure to the tobacco carcinogen, N-nitrosodimethylamine and
      benzopyrene, can disrupt VHL. According to in vitro and preclinical mouse
      studies, 2'-hydroxyflavanone can both protect the VHL locus and prevent the
      progression of VHL-mutant cancer. Human clinical trials examining the effect of
      supplementation of 2'-hydroxyflavanone, either alone or in combination with
      chemotherapeutic drugs, on RCC prevention have not been conducted, although there
      is considerable potential for 2'-hydroxyflavanone and its derivatives to be
      developed as RCC chemoprevention agents. Therefore, the discovery of plant
      derived cancer therapies, such as 2'-hydroxyflavanone, offers a new strategy for
      combating this highly resistant cancer. 

PMID- 25957658
TI  - A quantum mechanics-based halogen bonding scoring function for protein-ligand
      interactions.
AB  - A quantum mechanics-based scoring function for halogen bonding interaction,
      namely XBScore(QM), is developed based on 18,135 sets of geometrical and
      energetical parameters optimized at M06-2X/aug-cc-pVDZ level. Applying the
      function on typical halogen bonding systems from Protein Data Bank demonstrates
      its strong ability of predicting halogen bonding as attractive interaction with
      strength up to -4 kcal mol(-1). With a diverse set of proteins complexed with
      halogenated ligands, a systematic evaluation demonstrates the integrative
      advantage of XBScore(QM) over 12 other scoring functions on halogen bonding in
      four aspects, viz. pseudo docking power, ranking power, scoring power, and
      genuine docking power. Thus, this study not only provides a practicable scoring
      function of halogen bonding for high throughput virtual screening, but also
      serves as a benchmark for evaluating the performance of current scoring functions
      on characterizing halogen bonding. 

PMID- 25957663
TI  - Vaccines4Kids: Assessing the impact of text message reminders on immunization
      rates in infants.
AB  - The purpose of this study was to examine the effect text messages (TM)
      immunization reminders have on immunization rates in the first 7 months of life.
      This randomized-control trial enrolled 57 parent/infant dyads and had a 74%
      completion rate (43) at the end of the study period. The study was approved by
      Committee on Human Subjects at the University of Hawaii Institutional Board
      Review. All participants completed a demographics form and a Barriers to
      Immunization Survey (SHOTS survey) at the start and end of the study. Parents
      received TM at 4, 7, 12, 15, 20, & 23 weeks of child's age. The intervention
      group received immunization reminders and the control group received healthy baby
      messages. In the overall mixed model, between enrollment and 7 months of age, the
      barriers to immunizations decreased for all parents significantly. There were no
      significant differences in immunization rates between groups at 7 months of age.
      Positive responses from regarding TM interventions show this is a promising
      intervention, but further research is required regarding how to address behavior
      change and motivation for health prevention behaviors with TM. 

PMID- 25957662
TI  - Involvement of two microRNAs in the early immune response to DNA vaccination
      against a fish rhabdovirus.
AB  - Mechanisms that account for the high protective efficacy in teleost fish of a DNA
      vaccine expressing the glycoprotein (G) of Viral hemorrhagic septicemia virus
      (VHSV) are thought to involve early innate immune responses mediated by
      interferons (IFNs). Microribonucleic acids (miRNAs) are a diverse class of small
      (18-22 nucleotides) endogenous RNAs that potently mediate post-transcriptional
      silencing of a wide range of genes and are emerging as critical regulators of
      cellular processes, including immune responses. We have recently reported that
      miR-462 and miR-731 were strongly induced in rainbow trout infected with VHSV. In
      this study, we analyzed the expression of these miRNAs in fish following
      administration of the DNA vaccine and their potential functions. Quantitative RT
      PCR analysis revealed the increased levels of miR-462, and miR-731 in the
      skeletal muscle tissue at the site of vaccine administration and in the liver of
      vaccinated fish relative to empty plasmid backbone-injected controls. The
      increased expression of these miRNAs in the skeletal muscle correlated with the
      increased levels of the type I interferon (IFN)-inducible gene Mx, type I IFN and
      IFN-gamma genes at the vaccination site. Intramuscular injection of fish with
      either type I IFN or IFN-gamma plasmid construct resulted in the upregulation of
      miR-462 and miR-731 at the site of injection, suggesting that the induction of
      these miRNAs is elicited by IFNs. To analyze the function of miR-462 and miR-731,
      specific silencing of these miRNAs using anti-miRNA oligonucleotides was
      conducted in poly I:C-treated rainbow trout fingerlings. Following VHSV
      challenge, anti-miRNA-injected fish had faster development of disease and higher
      mortalities than control fish, indicating that miR-462/731 may be involved in IFN
      mediated protection conferred by poly I:C. 

PMID- 25957661
TI  - Synthesis of aryl dihydrothiazol acyl shikonin ester derivatives as anticancer
      agents through microtubule stabilization.
AB  - The high incidence of cancer and the side effects of traditional anticancer drugs
      motivate the search for new and more effective anticancer drugs. In this study,
      we synthesized 17 kinds of aryl dihydrothiazol acyl shikonin ester derivatives
      and evaluated their anticancer activity through MTT assay. Among them, C13 showed
      better antiproliferation activity with IC50=3.14 +/- 0.21 MUM against HeLa cells
      than shikonin (IC50=5.75 +/- 0.47 MUM). We then performed PI staining assay, cell
      cycle distribution, and cell apoptosis analysis for C13 and found that it can
      cause cell arrest in G2/M phase, which leads to cell apoptosis. This derivative
      can also reduce the adhesive ability of HeLa cells. Docking simulation and
      confocal microscopy assay results further indicated that C13 could bind well to
      the tubulin at paclitaxel binding site, leading to tubulin polymerization and
      mitotic disruption.

PMID- 25957665
TI  - Rotavirus landscape in Africa-Towards prevention and control: A report of the 8th
      African rotavirus symposium, Livingstone, Zambia.
AB  - The 8th African Rotavirus Symposium was held in Livingstone, Zambia from the 12
      13 June 2014. Over 130 delegates from 35 countries - 28 from African nations -
      participated in this symposium, which included scientists, clinicians,
      immunisation managers, public health officials, policymakers and vaccine
      manufacturers. The theme for the symposium was Rotavirus Landscape in Africa
      Towards Prevention and Control. At the time of the symposium, a total of 21
      African countries had introduced the rotavirus vaccine into their national
      immunisation schedules. This meeting was particularly timely and relevant to
      review early data on vaccine adoption and impact from these countries. The
      concluding panel discussion proposed several recommendations for areas of focus
      moving forward in rotavirus advocacy and research. 

PMID- 25957664
TI  - Epidemiological and genetic analysis of a 2014 outbreak of hepatitis A in Japan.
AB  - Hepatitis A virus (HAV) is one of the most common causes of feces-transmitted
      acute hepatitis worldwide. In Japan, most of HAV infections have been sporadic
      cases and a relatively low number of cases (approximately 100-150) of acute
      hepatitis A were reported in 2012 and 2013. However, in 2014, 342 cases were
      reported as of week 22. In order to characterize the viral agents causing this
      outbreak, we collected stool or sera (and both for three case) from patients with
      hepatitis A from many regions throughout Japan and performed genotyping of the
      VP1/P2A regions of HAV. We then used a multiple-alignment algorithm to compare
      the nucleotide sequences with those of reference strains. Phylogenetic tree
      analyses revealed that the 159 HAV isolates were divided into three subgenotypes:
      IA (137 cases), IB (4 cases), and IIIA (18 cases). The most unique feature of
      this outbreak was that for most subgenotype IA cases (103 out of 137 IA cases)
      the sequences analyzed shared 100% homology. Interestingly, the peak week for
      these IA infections was almost the same nationwide, suggesting that the epidemic
      of hepatitis A caused by this subgenotype IA strain may have expanded from a
      single source possibly because of one food-borne or waterborne source that was
      distributed nationwide at once. 

PMID- 25957666
TI  - Modular vaccine packaging increases packing efficiency.
AB  - BACKGROUND: Within a typical vaccine supply chain, vaccines are packaged into
      individual cylindrical vials (each containing one or more doses) that are bundled
      together in rectangular "inner packs" for transport via even larger groupings
      such as cold boxes and vaccine carriers. The variability of vaccine inner pack
      and vial size may hinder efficient vaccine distribution because it constrains
      packing of cold boxes and vaccine carriers to quantities that are often
      inappropriate or suboptimal in the context of country-specific vaccination
      guidelines. METHODS: We developed in Microsoft Excel (Microsoft Corp., Redmond,
      WA) a spreadsheet model that evaluated the impact of different packing schemes
      for the Benin routine regimen plus the introduction of the Rotarix vaccine.
      Specifically, we used the model to compare the current packing scheme to that of
      a proposed modular packing scheme. RESULTS: Conventional packing of a Dometic
      RCW25 that aims to maximize fully-immunized children (FICs) results in 123 FICs
      and a packing efficiency of 81.93% compared to a maximum of 155 FICs and 94.1%
      efficiency for an alternative modular packaging system. CONCLUSIONS: Our analysis
      suggests that modular packaging systems could offer significant advantages over
      conventional vaccine packaging systems with respect to space efficiency and
      potential FICs, when they are stored in standard vaccine carrying devices. This
      allows for more vaccines to be stored within the same volume while also
      simplifying the procedures used by field workers to pack storage devices.
      Ultimately, modular packaging systems could be a simple way to help increase
      vaccine coverage worldwide.

PMID- 25957667
TI  - Clinical management of patients with gastric neuroendocrine neoplasms associated
      with chronic atrophic gastritis.

PMID- 25957669
TI  - High salt intake: detrimental not only for blood pressure, but also for bone
      health?

PMID- 25957668
TI  - Steroidal contraceptive use is associated with lower bone mineral density in
      polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a common condition affecting reproductive
      aged women with features including hyperandrogenism and menstrual irregularity
      frequently treated with hormonal steroidal contraceptives. Women with PCOS appear
      to have lower bone mineral density (BMD). While steroidal contraceptives may
      positively affect bone health, their effect on BMD in PCOS is not known. The aim
      of this study was to assess BMD in women with PCOS according to recent
      contraceptive use. A cross-sectional analysis of 95 pre-menopausal overweight or
      obese sedentary women with PCOS [age 29.4 +/- 6.4 years, body mass index (BMI)
      36.1 +/- 5.3 kg/m(2)] who either recently took steroidal contraceptives (ceased 3
      months prior) or were not taking steroidal contraceptives was conducted. Clinical
      outcomes included BMD, anthropometry, insulin, glucose, reproductive hormones,
      dietary intake and vitamin use. BMD was significantly lower for women who used
      contraceptives compared to those who did not (mean difference 0.06 g/cm(2) 95 %
      confidence interval -0.11, -0.02, p = 0.005). In regression models, lower BMD was
      independently associated with contraceptive use (beta = -0.05, 95 % CI -0.094, 
      0.002, p = 0.042), higher testosterone (beta = -0.03, 95 % CI -0.05, -0.0008, p =
      0.043) and lower BMI (beta = 0.006, 95 % CI 0.002, 0.01, p = 0.007) (r (2) =
      0.22, p = 0.001 for entire model). We report for the first time that overweight
      and obese women with PCOS with recent steroidal contraceptive use had lower BMD
      in comparison to non-users independent of factors known to contribute to BMD.
      Whether this observation is directly related to steroidal contraceptive use or
      other factors requires further investigation.

PMID- 25957670
TI  - Clinical outcomes following hospital-wide implementation of prolonged-infusion
      cefepime and ceftazidime.

PMID- 25957671
TI  - Relationship between serum uric acid, metabolic syndrome and resting heart rate
      in Chinese elderly.
AB  - OBJECTIVE: Both serum uric acid (SUA) and resting heart rate (RHR) are positively
      associated with metabolic syndrome (MetS). However, little is known regarding the
      relationship between SUA and RHR. We aimed to investigate the relationship
      between SUA and RHR in the elderly with MetS. METHODS: With a retrospective
      observational analysis, 867 Chinese elderly subjects (437 males and 430 females)
      were divided into 4 groups according to SUA quartiles. We first investigated the
      relationship between SUA and MetS. Then we evaluated whether there is an
      independent association of SUA with RHR in these subjects. RESULTS: There were
      significant differences of MetS incidence in groups of Quartile 1-4 in male and
      female (all P<0.01). Female had higher MtS incidence than male (53.49% versus
      43.24%; P=0.003). After adjusting age, sex and diuretics usage, SUA levels
      intimately correlate with RHR, creatinine, waist-to-height ratio, waist
      circumference, high-sensitivity C-reactive protein (hsCRP) and white blood cells
      (all r>0.30, P<0.05). When RHR exceeded 86bpm, after adjusting for various known
      risk factors, Odds ratios of concomitant SUA level were 1.243, 1.908, and 2.194
      in the second, third, and fourth urate quartile respectively compared to the
      first quartile. ROC curve analysis demonstrated statistically significant value
      of RHR for hyperuricemia diagnosis (area under the curve was 0.702 with 95% CI of
      0.605-0.791, P=0.000). CONCLUSION: The SUA has significant correlation with RHR
      in MetS. RHR appears to be a potentially detective marker to predict the elevated
      SUA and cardio-metabolic risk in Chinese elderly.

PMID- 25957673
TI  - Predicting drug-target interaction for new drugs using enhanced similarity
      measures and super-target clustering.
AB  - Predicting drug-target interaction using computational approaches is an important
      step in drug discovery and repositioning. To predict whether there will be an
      interaction between a drug and a target, most existing methods identify similar
      drugs and targets in the database. The prediction is then made based on the known
      interactions of these drugs and targets. This idea is promising. However, there
      are two shortcomings that have not yet been addressed appropriately. Firstly,
      most of the methods only use 2D chemical structures and protein sequences to
      measure the similarity of drugs and targets respectively. However, this
      information may not fully capture the characteristics determining whether a drug
      will interact with a target. Secondly, there are very few known interactions,
      i.e. many interactions are "missing" in the database. Existing approaches are
      biased towards known interactions and have no good solutions to handle possibly
      missing interactions which affect the accuracy of the prediction. In this paper,
      we enhance the similarity measures to include non-structural (and non-sequence
      based) information and introduce the concept of a "super-target" to handle the
      problem of possibly missing interactions. Based on evaluations on real data, we
      show that our similarity measure is better than the existing measures and our
      approach is able to achieve higher accuracy than the two best existing
      algorithms, WNN-GIP and KBMF2K. Our approach is available at
      http://web.hku.hk/~liym1018/projects/drug/drug.html or
      http://www.bmlnwpu.org/us/tools/PredictingDTI_S2/METHODS.html. 

PMID- 25957672
TI  - A comparative study of the human urinary mycotoxin excretion patterns in
      Bangladesh, Germany, and Haiti using a rapid and sensitive LC-MS/MS approach.
AB  - An improved "dilute and shoot" LC-MS/MS multibiomarker approach was used to
      monitor urinary excretion of 23 mycotoxins and their metabolites in human
      populations from Asia (Bangladesh), Europe (Germany), and the Caribbean region
      (Haiti). Deoxynivalenol (DON), deoxynivalenol-3-glucuronide (DON-3-GlcA), T-2
      toxin (T-2), HT-2-toxin (HT-2), HT-2-toxin-4-glucuronide (HT-2-4-GlcA), fumonisin
      B1 (FB1), aflatoxins (AFB1, AFB2, AFG1, AFG2, AFM1), zearalenone (ZEA),
      zearalanone (ZAN), their urinary metabolites alpha-zearalanol (alpha-ZEL) and
      beta-zearalanol (beta-ZEL), and corresponding 14-O-glucuronic acid conjugates
      (ZEA-14-GlcA, ZAN-14-GlcA, beta-ZEL, alpha/beta-ZEL-14-GlcA), ochratoxin A (OTA),
      and ochratoxin alpha (OTalpha) as well as enniatin B (EnB) and dihydrocitrinone
      (DH-CIT) were among these compounds. Eight urinary mycotoxin biomarkers were
      detected (AFM1, DH-CIT, DON, DON-GLcA, EnB, FB1, OTA, and alpha-ZEL). DON and DON
      GlcA were exclusively detected in urines from Germany and Haiti whereas urinary
      OTA and DH-CIT concentrations were significantly higher in Bangladeshi samples.
      AFM1 was present in samples from Bangladesh and Haiti only. Exposure was
      estimated by the calculation of probable daily intakes (PDI), and estimates
      suggested occasional instances of toxin intakes that exceed established tolerable
      daily intakes (TDI). The detection of individual mycotoxin exposure by biomarker
      based approaches is a meaningful addition to the classical monitoring of the
      mycotoxin content of the food supply.

PMID- 25957674
TI  - Measuring the neutralization potency of influenza A virus hemagglutinin
      stalk/stem-binding antibodies in polyclonal preparations by microneutralization
      assay.
AB  - The discovery of broadly-neutralizing antibodies that bind to the hemagglutinin
      stalk/stem domain has opened exciting new avenues for the development of
      "universal" influenza virus vaccines and therapeutics. Unlike strain-specific
      antibodies which bind to the hemagglutinin head domain and inhibit receptor
      binding, antibodies that bind to the stalk domain function to inhibit later
      stages of infection. The hemagglutination inhibition assay has long been the
      standard for evaluating titers of neutralizing hemagglutinin-specific antibodies
      in serum. The assay has the beneficial properties of being relatively rapid, easy
      to-perform, and requires very little specialized equipment. Historically,
      hemagglutination inhibition titers of 40 or above against a given strain of
      influenza has been considered a correlate of protection on a population level.
      Unfortunately, this assay cannot be used to measure titers of hemagglutinin stalk
      specific antibodies due to their lack of hemagglutination inhibiting activity.
      This has necessitated the development of novel reagents and assays capable of
      sensitive and specific detection of broadly-neutralizing HA stalk-binding
      antibodies in polyclonal mixtures. Here, we describe a novel microneutralization
      based assay that utilizes recombinant influenza A viruses expressing chimeric
      hemagglutinin molecules and 'exotic' neuraminidase to measure titers of broadly
      neutralizing antibodies in polyclonal preparations. 

PMID- 25957675
TI  - In tight times, companies fill the funding gap.
AB  - With federal budgets under pressure, scientists turn to corporations for research
      support. 

PMID- 25957676
TI  - Figuring fact from fiction: unbiased polling of memory T cells.
AB  - Immunization generates several memory T cell subsets that differ in their
      migratory properties, anatomic distribution, and, hence, accessibility to
      investigation. In this issue, Steinert et al. demonstrate that what was believed
      to be a minor memory cell subset in peripheral tissues has been dramatically
      underestimated. Thus, current models of protective immunity require revision.

PMID- 25957677
TI  - Shedding light on glioma growth.
AB  - Cancer is known for opportunistically utilizing resources from its surroundings
      for its own growth and survival. In this issue of Cell, Venkatesh et al.
      demonstrate that this also occurs in the brain, identifying neuronal activity
      induced secretion of neuroligin-3 as a novel mechanism promoting glioma
      proliferation.

PMID- 25957678
TI  - Rods Feed Cones to Keep them Alive.
AB  - Cone photoreceptors, responsible for high-resolution and color vision,
      progressively degenerate following the death of rod photoreceptors in the
      blinding disease retinitis pigmentosa. Ait-Ali et al. describe a molecular
      mechanism by which RdCVF, a factor normally released by rods, controls glucose
      entry into cones, enhancing their survival.

PMID- 25957679
TI  - Three Cell Fusions during Double Fertilization.
AB  - Fertilization of both egg and central cell is a major distinguishing feature of
      flowering plants. Now, Maruyama et al. report a third cell fusion event between
      the persistent synergid and the fertilized central cell shortly after double
      fertilization in Arabidopsis. This causes rapid dilution of pollen tube
      attractant(s), preventing polytubey. 

PMID- 25957681
TI  - Genesis of chromatin and transcription dynamics in the origin of species.
AB  - Histone proteins compact and stabilize the genomes of Eukarya and Archaea. By
      forming nucleosome(-like) structures they restrict access of DNA-binding
      transcription regulators to cis-regulatory DNA elements. Dynamic competition
      between histones and transcription factors is facilitated by different classes of
      proteins including ATP-dependent remodeling enzymes that control assembly,
      access, and editing of chromatin. Here, we summarize the knowledge on dynamics
      underlying transcriptional regulation across the domains of life with a focus on
      ATP-dependent enzymes in chromatin structure or in TATA-binding protein activity.
      These insights suggest directions for future studies on the evolution of
      transcription regulation and chromatin dynamics. 

PMID- 25957680
TI  - Making sense of transcription networks.
AB  - When transcription regulatory networks are compared among distantly related
      eukaryotes, a number of striking similarities are observed: a larger-than
      expected number of genes, extensive overlapping connections, and an apparently
      high degree of functional redundancy. It is often assumed that the complexity of
      these networks represents optimized solutions, precisely sculpted by natural
      selection; their common features are often asserted to be adaptive. Here, we
      discuss support for an alternative hypothesis: the common structural features of
      transcription networks arise from evolutionary trajectories of "least resistance"
      -that is, the relative ease with which certain types of network structures are
      formed during their evolution.

PMID- 25957682
TI  - Quantifying Memory CD8 T Cells Reveals Regionalization of Immunosurveillance.
AB  - Memory CD8 T cells protect against intracellular pathogens by scanning host cell
      surfaces; thus, infection detection rates depend on memory cell number and
      distribution. Population analyses rely on cell isolation from whole organs, and
      interpretation is predicated on presumptions of near complete cell recovery.
      Paradigmatically, memory is parsed into central, effector, and resident subsets,
      ostensibly defined by immunosurveillance patterns but in practice identified by
      phenotypic markers. Because isolation methods ultimately inform models of memory
      T cell differentiation, protection, and vaccine translation, we tested their
      validity via parabiosis and quantitative immunofluorescence microscopy of a mouse
      memory CD8 T cell population. We report three major findings: lymphocyte
      isolation fails to recover most cells and biases against certain subsets,
      residents greatly outnumber recirculating cells within non-lymphoid tissues, and
      memory subset homing to inflammation does not conform to previously hypothesized
      migration patterns. These results indicate that most host cells are surveyed for
      reinfection by segregated residents rather than by recirculating cells that
      migrate throughout the blood and body.

PMID- 25957683
TI  - IL-7-Induced Glycerol Transport and TAG Synthesis Promotes Memory CD8+ T Cell
      Longevity.
AB  - Memory T cells are critical for long-term immunity against reinfection and
      require interleukin-7 (IL-7), but the mechanisms by which IL-7 controls memory T
      cell survival, particularly metabolic fitness, remain elusive. We discover that
      IL-7 induces expression of the glycerol channel aquaporin 9 (AQP9) in virus
      specific memory CD8+ T cells, but not naive cells, and that AQP9 is vitally
      required for their long-term survival. AQP9 deficiency impairs glycerol import
      into memory CD8+ T cells for fatty acid esterification and triglyceride (TAG)
      synthesis and storage. These defects can be rescued by ectopic expression of TAG
      synthases, which restores lipid stores and memory T cell survival. Finally, we
      find that TAG synthesis is a central component of IL-7-mediated survival of human
      and mouse memory CD8+T cells. This study uncovers the metabolic mechanisms by
      which IL-7 tailors the metabolism of memory T cells to promote their longevity
      and fast response to rechallenge.

PMID- 25957684
TI  - Non-coding RNA Generated following Lariat Debranching Mediates Targeting of AID
      to DNA.
AB  - Transcription through immunoglobulin switch (S) regions is essential for class
      switch recombination (CSR), but no molecular function of the transcripts has been
      described. Likewise, recruitment of activation-induced cytidine deaminase (AID)
      to S regions is critical for CSR; however, the underlying mechanism has not been
      fully elucidated. Here, we demonstrate that intronic switch RNA acts in trans to
      target AID to S region DNA. AID binds directly to switch RNA through G
      quadruplexes formed by the RNA molecules. Disruption of this interaction by
      mutation of a key residue in the putative RNA-binding domain of AID impairs
      recruitment of AID to S region DNA, thereby abolishing CSR. Additionally,
      inhibition of RNA lariat processing leads to loss of AID localization to S
      regions and compromises CSR; both defects can be rescued by exogenous expression
      of switch transcripts in a sequence-specific manner. These studies uncover an RNA
      mediated mechanism of targeting AID to DNA. 

PMID- 25957685
TI  - RNA exosome-regulated long non-coding RNA transcription controls super-enhancer
      activity.
AB  - We have ablated the cellular RNA degradation machinery in differentiated B cells
      and pluripotent embryonic stem cells (ESCs) by conditional mutagenesis of core
      (Exosc3) and nuclear RNase (Exosc10) components of RNA exosome and identified a
      vast number of long non-coding RNAs (lncRNAs) and enhancer RNAs (eRNAs) with
      emergent functionality. Unexpectedly, eRNA-expressing regions accumulate R-loop
      structures upon RNA exosome ablation, thus demonstrating the role of RNA exosome
      in resolving deleterious DNA/RNA hybrids arising from active enhancers. We have
      uncovered a distal divergent eRNA-expressing element (lncRNA-CSR) engaged in long
      range DNA interactions and regulating IgH 3' regulatory region super-enhancer
      function. CRISPR-Cas9-mediated ablation of lncRNA-CSR transcription decreases its
      chromosomal looping-mediated association with the IgH 3' regulatory region super
      enhancer and leads to decreased class switch recombination efficiency. We propose
      that the RNA exosome protects divergently transcribed lncRNA expressing enhancers
      by resolving deleterious transcription-coupled secondary DNA structures, while
      also regulating long-range super-enhancer chromosomal interactions important for
      cellular function.

PMID- 25957686
TI  - Endogenous tRNA-Derived Fragments Suppress Breast Cancer Progression via YBX1
      Displacement.
AB  - Upon exposure to stress, tRNAs are enzymatically cleaved, yielding distinct
      classes of tRNA-derived fragments (tRFs), yielding distinct classes of tRFs. We
      identify a novel class of tRFs derived from tRNA(Glu), tRNA(Asp), tRNA(Gly), and
      tRNA(Tyr) that, upon induction, suppress the stability of multiple oncogenic
      transcripts in breast cancer cells by displacing their 3' untranslated regions
      (UTRs) from the RNA-binding protein YBX1. This mode of post-transcriptional
      silencing is sequence specific, as these fragments all share a common motif that
      matches the YBX1 recognition sequence. Loss-of-function and gain-of-function
      studies, using anti-sense locked-nucleic acids (LNAs) and synthetic RNA mimetics,
      respectively, revealed that these fragments suppress growth under serum
      starvation, cancer cell invasion, and metastasis by breast cancer cells. Highly
      metastatic cells evade this tumor-suppressive pathway by attenuating the
      induction of these tRFs. Our findings reveal a tumor-suppressive role for
      specific tRNA-derived fragments and describe a molecular mechanism for their
      action. This transcript displacement-based mechanism may generalize to other
      tRNA, ribosomal-RNA, and sno-RNA fragments. 

PMID- 25957687
TI  - Rod-derived cone viability factor promotes cone survival by stimulating aerobic
      glycolysis.
AB  - Rod-derived cone viability factor (RdCVF) is an inactive thioredoxin secreted by
      rod photoreceptors that protects cones from degeneration. Because the secondary
      loss of cones in retinitis pigmentosa (RP) leads to blindness, the administration
      of RdCVF is a promising therapy for this untreatable neurodegenerative disease.
      Here, we investigated the mechanism underlying the protective role of RdCVF in
      RP. We show that RdCVF acts through binding to Basigin-1 (BSG1), a transmembrane
      protein expressed specifically by photoreceptors. BSG1 binds to the glucose
      transporter GLUT1, resulting in increased glucose entry into cones. Increased
      glucose promotes cone survival by stimulation of aerobic glycolysis. Moreover, a
      missense mutation of RdCVF results in its inability to bind to BSG1, stimulate
      glucose uptake, and prevent secondary cone death in a model of RP. Our data
      uncover an entirely novel mechanism of neuroprotection through the stimulation of
      glucose metabolism. 

PMID- 25957688
TI  - Structural snapshots of actively translating human ribosomes.
AB  - Macromolecular machines, such as the ribosome, undergo large-scale conformational
      changes during their functional cycles. Although their mode of action is often
      compared to that of mechanical machines, a crucial difference is that, at the
      molecular dimension, thermodynamic effects dominate functional cycles, with
      proteins fluctuating stochastically between functional states defined by
      energetic minima on an energy landscape. Here, we have used cryo-electron
      microscopy to image ex-vivo-derived human polysomes as a source of actively
      translating ribosomes. Multiparticle refinement and 3D variability analysis
      allowed us to visualize a variety of native translation intermediates.
      Significantly populated states include not only elongation cycle intermediates in
      pre- and post-translocational states, but also eEF1A-containing decoding and
      termination/recycling complexes. Focusing on the post-translocational state, we
      extended this assessment to the single-residue level, uncovering striking details
      of ribosome-ligand interactions and identifying both static and functionally
      important dynamic elements. 

PMID- 25957689
TI  - Mitochondrial ClpX Activates a Key Enzyme for Heme Biosynthesis and
      Erythropoiesis.
AB  - The mitochondrion maintains and regulates its proteome with chaperones primarily
      inherited from its bacterial endosymbiont ancestor. Among these chaperones is the
      AAA+ unfoldase ClpX, an important regulator of prokaryotic physiology with poorly
      defined function in the eukaryotic mitochondrion. We observed phenotypic
      similarity in S. cerevisiae genetic interaction data between mitochondrial ClpX
      (mtClpX) and genes contributing to heme biosynthesis, an essential mitochondrial
      function. Metabolomic analysis revealed that 5-aminolevulinic acid (ALA), the
      first heme precursor, is 5-fold reduced in yeast lacking mtClpX activity and that
      total heme is reduced by half. mtClpX directly stimulates ALA synthase in vitro
      by catalyzing incorporation of its cofactor, pyridoxal phosphate. This activity
      is conserved in mammalian homologs; additionally, mtClpX depletion impairs
      vertebrate erythropoiesis, which requires massive upregulation of heme
      biosynthesis to supply hemoglobin. mtClpX, therefore, is a widely conserved
      stimulator of an essential biosynthetic pathway and uses a previously
      unrecognized mechanism for AAA+ unfoldases.

PMID- 25957690
TI  - Widespread Proteome Remodeling and Aggregation in Aging C. elegans.
AB  - Aging has been associated with a progressive decline of proteostasis, but how
      this process affects proteome composition remains largely unexplored. Here, we
      profiled more than 5,000 proteins along the lifespan of the nematode C. elegans.
      We find that one-third of proteins change in abundance at least 2-fold during
      aging, resulting in a severe proteome imbalance. These changes are reduced in the
      long-lived daf-2 mutant but are enhanced in the short-lived daf-16 mutant. While
      ribosomal proteins decline and lose normal stoichiometry, proteasome complexes
      increase. Proteome imbalance is accompanied by widespread protein aggregation,
      with abundant proteins that exceed solubility contributing most to aggregate
      load. Notably, the properties by which proteins are selected for aggregation
      differ in the daf-2 mutant, and an increased formation of aggregates associated
      with small heat-shock proteins is observed. We suggest that sequestering proteins
      into chaperone-enriched aggregates is a protective strategy to slow proteostasis
      decline during nematode aging.

PMID- 25957692
TI  - SnapShot: Insulin/IGF1 Signaling.
AB  - The insulin/IGF1signaling pathway (ISP) plays an essential role in long-term
      health. Some perturbations in this pathway are associated with diseases such as
      type 2 diabetes; other perturbations extend lifespan in worms, flies, and mice.
      The ISP regulates many biological processes, including energy storage, apoptosis,
      transcription, and cellular homeostasis. Such regulation involves precise
      rewiring of temporal events in protein phosphorylation networks. For an animated
      version of this Enhanced SnapShot, please visit
      http://www.cell.com/cell/enhanced/odonoghue. 

PMID- 25957691
TI  - Prospective derivation of a living organoid biobank of colorectal cancer
      patients.
AB  - In Rspondin-based 3D cultures, Lgr5 stem cells from multiple organs form ever
      expanding epithelial organoids that retain their tissue identity. We report the
      establishment of tumor organoid cultures from 20 consecutive colorectal carcinoma
      (CRC) patients. For most, organoids were also generated from adjacent normal
      tissue. Organoids closely recapitulate several properties of the original tumor.
      The spectrum of genetic changes within the "living biobank" agrees well with
      previous large-scale mutational analyses of CRC. Gene expression analysis
      indicates that the major CRC molecular subtypes are represented. Tumor organoids
      are amenable to high-throughput drug screens allowing detection of gene-drug
      associations. As an example, a single organoid culture was exquisitely sensitive
      to Wnt secretion (porcupine) inhibitors and carried a mutation in the negative
      Wnt feedback regulator RNF43, rather than in APC. Organoid technology may fill
      the gap between cancer genetics and patient trials, complement cell-line- and
      xenograft-based drug studies, and allow personalized therapy design. PAPERCLIP.

PMID- 25957693
TI  - Pulsatile tinnitus and an unusual ossicular anomaly.

PMID- 25957694
TI  - Metagenetic tools for the census of marine meiofaunal biodiversity: An overview.
AB  - Marine organisms belonging to meiofauna (size range: 20-500 MUm) are amongst the
      most abundant and highly diversified metazoans on Earth including 22 over 35
      known animal Phyla and accounting for more than 2/3 of the abundance of metazoan
      organisms. In any marine system, meiofauna play a key role in the functioning of
      the food webs and sustain important ecological processes. Estimates of meiofaunal
      biodiversity have been so far almost exclusively based on morphological analyses,
      but the very small size of these organisms and, in some cases, the insufficient
      morphological distinctive features limit considerably the census of the
      biodiversity of this component. Molecular approaches recently applied also to
      small invertebrates (including meiofauna) can offer a new momentum for the census
      of meiofaunal biodiversity. Here, we provide an overview on the application of
      metagenetic approaches based on the use of next generation sequencing platforms
      to study meiofaunal biodiversity, with a special focus on marine nematodes. Our
      overview shows that, although such approaches can represent a useful tool for the
      census of meiofaunal biodiversity, there are still different shortcomings and
      pitfalls that prevent their extensive use without the support of the classical
      taxonomic identification. Future investigations are needed to address these
      problems and to provide a good match between the contrasting findings emerging
      from classical taxonomic and molecular/bioinformatic tools.

PMID- 25957695
TI  - A transcriptome resource for Antarctic krill (Euphausia superba Dana) exposed to
      short-term stress.
AB  - Euphausia superba is a keystone species in Antarctic food webs. However, the
      continued decrease in stock density raises concerns over the resilience and
      adaptive potential of krill to withstand the current rate of environmental
      change. We undertook a transcriptome-scale approach (454 pyrosequencing) as a
      baseline for future studies addressing the physiological response of krill to
      short-term food shortage and natural UV-B stress. The final assembly resulted in
      a total of 26,415 contigs, 39.8% of which were putatively annotated. Exploratory
      analyses indicate an overall reduction in protein synthesis under food shortage
      while UV stress resulted in the activation of photo-protective mechanisms. 

PMID- 25957696
TI  - Draft genome sequence of Vitellibacter vladivostokensis KMM 3516(T): a protease
      producing bacterium.
AB  - Type strain Vitellibacter vladivostokensis KMM 3516(T) (=NBRC 16718(T)) belongs
      to the phylum Cytophaga-Flavobacterium-Bacteroides. To date, no genomes of the
      Vitellibacter spp. have been reported, and their metabolic pathways are unknown.
      This study reports the draft genome sequence of V. vladivostokensis. Moreover,
      mining of genes associated with proteolytic enzymes was performed to provide
      insights for further enzyme characterization. 

PMID- 25957698
TI  - Night or darkness, which intensifies the feeling of fear?
AB  - Nighttime fear is a phenomenon in which people feel more afraid of threats at
      night. Despite the vast amount of psychological research on nighttime fear,
      previous researchers have not accurately distinguished between "night" and
      "darkness", both of which play important roles in nighttime fear. We collected
      physiological (skin conductance response and heart rate) and psychological (self
      report) data simultaneously to investigate the effects of "night" and "darkness"
      on fearful feelings and whether these effects were moderated by the mode of
      stimulus delivery (i.e., visual or auditory). Specifically, two tasks were
      employed in which time (day vs. night), illumination (light vs. darkness) and
      stimulus type (fearful vs. neutral) were manipulated. Participants (n=128) were
      exposed to visual and auditory oddball tasks consisting of fearful and neutral
      stimuli. The results indicated that there were significant increases in fear
      responses at night, and the difference between day and night was significant for
      fear stimuli but not for neutral events. Furthermore, these effects were
      consistent over different sensory modalities (visual and auditory). The results
      of this study underscore the importance of the day-night cycle in fear-related
      information processing and suggest that further attention needs to be paid to the
      influence of the biological circadian rhythm on these processes. The current
      findings could inform a deeper understanding of anxiety and fear-related
      disorders, and thus, we invite future studies to illuminate the underlying
      neurobiological mechanisms therein. 

PMID- 25957697
TI  - Smoking's effects on respiratory sinus arrhythmia in adolescent smokers.
AB  - Respiratory sinus arrhythmia (RSA) has emerged as an indicator of how well the
      body maintains homeostasis and flexibly responds to environmental demands.
      Previous research has shown that smoking has both acute and chronic effects on
      RSA in adults. More recent work has focused on adolescent smokers because the
      natural decrease in RSA over the lifespan might be hastened by smoking at an
      early age. The goal of the current study, then, was to examine the acute effects
      of smoking on RSA and mean heart rate (HR) in a group of adolescent smokers.
      Participants completed two experimental sessions separated by 6-10 weeks, during
      which resting electrocardiogram (EKG) data were collected before and after
      smoking or not smoking a single cigarette ad libitum. Results indicate that
      smoking significantly decreased resting RSA and increased mean HR. In addition,
      those who smoked their first cigarette earlier in life (i.e., before age 8 or 10)
      evidenced a greater decrease in RSA during their smoking session relative to
      those who tried smoking after age 10. Importantly, these findings are largely
      consistent with the adult literature and suggest that smoking has acute effects
      on both RSA and HR in adolescence.

PMID- 25957699
TI  - Nasal delivery of analgesic ketorolac tromethamine thermo- and ion-sensitive in
      situ hydrogels.
AB  - Ketorolac tromethamine (KT) was potent to treat moderate to moderately severe
      pains. However, KT solutions for nasal delivery lost quickly from the nasal
      route. Thermo- and ion-sensitive in-situ hydrogels (ISGs) are appropriate for
      nasal drug delivery because the intranasal temperature maintains ~37  degrees C
      and nasal fluids consist of plentiful cations. In this study, a novel nasal
      thermo- and ion-sensitive ISG of KT was prepared with thermo-sensitive poloxamer
      407 (P407) and ion-sensitive deacetylated gellan gum (DGG). The optimal
      formulation of the KT ISG consisted of 3% (w/v) DGG and 18% (w/v) P407 and its
      viscosity was up to 7.63 Pas at 37  degrees C. Furthermore, penetration enhancers
      and bacterial inhibitors were added and their fractions in the ISG were optimized
      based on transmucosal efficiencies and toxicity on toad pili. Sulfobutyl ether
      beta-cyclodextrin of 2.5% (w/v) and chlorobutanol of 0.5% (w/v) were chosen as
      the penetration enhancer and the bacterial inhibitor, respectively. The Fick's
      diffusion and dissolution of KT could drive it continuous release from the dually
      sensitive ISG according to the in vitro investigation. Two methods, writhing
      frequencies induced by acetic acid and latency time of tails retracting from hot
      water, were used to evaluate the pharmacodynamics of the KT ISG on the mouse
      models. The writhing frequencies significantly decreased and the latency time of
      tail retracting was obviously prolonged (p<0.05) for the KT ISG compared to the
      control. The thermo- and ion-sensitive KT ISG had appropriate gelation
      temperature, sustained drug release, improved intranasal absorption, obvious
      pharmacodynamic effect, and negligible nasal ciliotoxicity. It is a promising
      intranasal analgesic formulation.

PMID- 25957700
TI  - Preparation and characterization of the ion-fixed mixed micelles with superior
      stability.
AB  - The inherent instability of micelles remains a main challenge for antitumor drug
      delivery, the objective of this study is to prepare and characterize the ion
      fixed mixed micelles with significantly improved stability. The mixed micelles
      and ion-fixed mixed micelles combining the carboxy-containing PLA (PLA-COO(-))
      and mPEG-PLA were formed by inserting PLA-COO(-) into micellar core without and
      with metal ions, respectively. The critical micelle concentration (CMC) of mixed
      micelle depended on the origin PLA length in the mPEG-PLA, whereas kinetic
      stability of the mixed micelles was significantly improved, irrespective of the
      PLA length. However, curcumin (Cur)-loaded mixed micelles did not show higher
      physical stability upon dilution and Cur-micelle bonding constant due to the
      lower loading space. On the contrary, the ion-fixed mixed micelles formed in the
      presence of CaCl2 solution showed a high physical stability upon dilution due to
      the solidification of micellar core by forming the more hydrophobic (PLA-COO(-))2
      Ca(2+) complex. The Cur-loaded ion-fixed mixed micelles showed the comparable
      cellular uptake of Cur and cytotoxicity in comparison with mPEG-PLA micelles. Our
      study highlights a universal combining strategy of ion-fixed mixed micelles with
      superior stability to individual micelles for antitumor drug delivery. 

PMID- 25957701
TI  - Supercritical fluid assisted production of micrometric powders of the labile
      trypsin and chitosan/trypsin composite microparticles.
AB  - Supercritical fluid assisted atomization introduced by a hydrodynamic cavitation
      mixer (SAA-HCM) was used to prepare micrometric particles of a labile protein,
      i.e., trypsin from aqueous solution without use of any organic solvents. The
      trypsin particles precipitated had various morphologies under different process
      conditions, with particle diameters ranging from 0.2 to 4 MUm. FTIR, SDS-PAGE, CD
      and fluorescence spectra were performed to analyze the structural stability of
      the protein, and trypsin retained above 70% of the biological activity. Besides,
      chitosan was selected as the polymer carrier in an effort to prepare trypsin
      composite microparticles via SAA-HCM process. The influences of chitosan
      molecular weight, polymer/protein ratio and solution concentration on the
      particle morphology and size distribution were investigated in detail. Non
      coalescing spherical composite microparticles with a narrow particle distribution
      (0.2-3 MUm) could be obtained. The SAA-HCM prepared particles were amorphous as
      demonstrated by XRD and had a loading efficiency about 90%. The protein release
      profiles of the composite microparticles were evaluated using both the immersion
      condition and a Franz diffusion cell. Finally, the distribution of the protein
      within the particles was characterized through CLSM analysis of FITC-labeled
      trypsin-loaded chitosan microparticles. The SAA-HCM process is demonstrated to be
      a protein-friendly and promising technique for production of protein and
      polymer/protein composite particles formulations from aqueous solutions for drug
      delivery systems.

PMID- 25957702
TI  - Liposomes containing cholesterol analogues of botanical origin as drug delivery
      systems to enhance the oral absorption of insulin.
AB  - In fear of animal-associated diseases, there is a trend in searching for non
      animal derived substitutes for existing excipients in the pharmaceutical
      industries. This paper aimed to screen cholesterol analogues as membrane
      stabilizers of liposomes from botanical sterols, including beta-sitosterol,
      stigmasterol, ergosterol and lanosterol. Liposomes containing four kinds of
      sterols were prepared and evaluated in vitro and in vivo as oral delivery system
      of insulin. Liposomes containing beta-sitosterol (Si-Lip), stigmasterol (St-Lip)
      and lanosterol (La-Lip) was found not to protect insulin against degradation.
      Only 10% of the initial insulin in liposomes was preserved after a 30 min
      exposure to simulated gastric fluids. However, the protective ability of
      liposomes containing ergosterol (Er-Lip) was similar to that of liposomes
      containing sodium glycocholate (Sgc-Lip) and superior to that of liposomes
      containing cholesterol (Ch-Lip). In addition, the blood glucose level can
      decrease to about 50% of initial level after oral Er-Lip which was significantly
      superior to the in vivo performance of Si-Lip and Ch-Lip and similar to Sgc-Lip.
      Er-Lips of ergosterol/phospholipids ratios of 1:4 or 1:6 exerts more pronounced
      protective ability of insulin in simulated gastrointestinal fluids and
      hypoglycemic effects in rats than other formulations. Furthermore, Er-Lips
      exerted low toxicity to Caco-2 cells through a cell viability study. Meahwhile,
      insulin permeability was significantly increased across Caco-2 monolayers by
      encapsulating in Er-Lip. It was concluded that ergosterol could be used as a
      substitute for cholesterol and bile salt derivatives in liposomes to enhance oral
      bioavailability of insulin.

PMID- 25957703
TI  - Curcumin-piperine mixtures in self-microemulsifying drug delivery system for
      ulcerative colitis therapy.
AB  - Curcumin (CUR) is a poorly water-soluble drug and its absorption is very low. In
      this study, CUR and piperine (PIP) were co-encapsulated into the nanoformulation
      called self-microemulsifying drug delivery system (SMEDDS) to improve the
      stability and water-solubility of CUR and enhance its anti-colitis activity. The
      formulation of CUR-PIP-SMEDDS was prepared to encapsulate two hydrophobic
      components CUR and PIP, and then was characterized by assessing appearance,
      morphology, particle size, zeta potential and drug encapsulation efficiency. The
      appearance of CUR-PIP-SMEDDS remained clarified and transparent, and the
      microemulsion droplets appeared spherical without aggregation. The mean size of
      microemulsion droplet formed from CUR-PIP-SMEDDS was 15.87 +/- 0.76 nm, and the
      drug encapsulation efficiency of SMEDDS for CUR and PIP were (94.34 +/- 2.18)%
      and (90.78 +/- 2.56)%, respectively. The vitro stability investigation of CUR-PIP
      SMEDDS in colon tissue suggested that using SMEDDS as a delivery vehicle and co
      encapsulated with PIP, CUR was more stable than drug solution in colons site.
      Meanwhile, the anti-inflammatory activity of CUR-PIP-SMEDDS was evaluated on DSS
      induced colitis model. The results showed that CUR-PIP-SMEDDS exhibited definite
      anti-colitis activity by directing CUR-PIP-SMEDDS to inflammatory colon tissue
      through retention enema administration. Our study illustrated that the developed
      CUR-PIP-SMEDDS formulation was a potential carrier for developing colon-specific
      drug delivery system of CUR for ulcerative colitis treatment.

PMID- 25957704
TI  - Taste masked thin films printed by jet dispensing.
AB  - Taste masking of bitter active substances is an emerging area in the
      pharmaceutical industry especially for paediatric/geriatric medications. In this
      study we introduce the use of jet dispensing as a taste masking technology by
      printing mucosal thin films of three model bitter substances, Cetirizine HCl,
      Diphenylhydramine HCl and Ibuprofen. The process was used to dispense aqueous
      drugs/polymer solutions at very high speed where eventually the drugs were
      embedded in the polymer matrix. The in vivo evaluation of jet-dispensed mucosal
      films showed excellent taste masking for drug loadings from 20 to 40%. Jet
      dispensing was proved to make uniform, accurate and reproducible thin films with
      excellent content uniformity. 

PMID- 25957705
TI  - The biopharmaceutics of successful controlled release drug product: Segmental
      dependent permeability of glipizide vs. metoprolol throughout the intestinal
      tract.
AB  - The purpose of this work was to study the challenges and prospects of regional
      dependent absorption in a controlled-release scenario, through the oral
      biopharmaceutics of the sulfonylurea antidiabetic drug glipizide. The BCS
      solubility class of glipizide was determined, and its physicochemical properties
      and intestinal permeability were thoroughly investigated, both in-vitro (PAMPA
      and Caco-2) and in-vivo in rats. Metoprolol was used as the low/high permeability
      class boundary marker. Glipizide was found to be a low-solubility compound. All
      intestinal permeability experimental methods revealed similar trend; a mirror
      image small intestinal permeability with opposite regional/pH-dependency was
      obtained, a downward trend for glipizide, and an upward trend for metoprolol. Yet
      the lowest permeability of glipizide (terminal Ileum) was comparable to the
      lowest permeability of metoprolol (proximal jejunum). At the colon, similar
      permeability was evident for glipizide and metoprolol, that was higher than
      metoprolol's jejunal permeability. We present an analysis that identifies
      metoprolol's jejunal permeability as the low/high permeability class benchmark
      anywhere throughout the intestinal tract; we show that the permeability of both
      glipizide and metoprolol matches/exceeds this threshold throughout the entire
      intestinal tract, accounting for their success as controlled-release dosage form.
      This represents a key biopharmaceutical characteristic for a successful
      controlled-release dosage form. 

PMID- 25957707
TI  - Isolated congenital maxillomandibular synechiae.
AB  - INTRODUCTION: Congenital maxillomandibular syngnathia, or fusion of the jaws, is
      a rare condition that has a broad spectrum of presentations. The restricted mouth
      opening can lead to issues with feeding, swallowing, and respiration resulting in
      failure to thrive and temporomandibular joint ankylosis. Early recognition and
      treatment is necessary for proper growth and development. CASE REPORT: We report
      a 1-day-old male with isolated bilateral soft tissue alveolar fibrous bands. He
      presented with difficulty feeding secondary to trismus. No bony or muscular
      involvement in the synechiae was noted and the remainder of the physical exam was
      unremarkable. The bilateral alveolar synechiae were divided under local
      anesthesia using surgical scissors. The patient immediately showed improvement in
      mouth opening and had resolution of his feeding problems. He is now gaining
      weight and developing appropriately. DISCUSSION: The accompanying review of the
      literature demonstrates only 11 cases worldwide of isolated maxillomandibular
      fusion. Depending upon the composition of the synechiae, simple surgical division
      under local anesthesia can be curative.

PMID- 25957706
TI  - Cystic fibrosis-related bone disease in children: Examination of peripheral
      quantitative computed tomography (pQCT) data.
AB  - BACKGROUND: The investigation of skeletal health data beyond dual X-ray
      absorptiometry (DXA) is limited in young individuals with CF. We assessed
      volumetric bone mineral densities (BMD), and bone and muscle parameters using
      peripheral quantitative computed tomography (pQCT) in individuals with CF and
      controls, 7.00-17.99 years. METHODS: Peripheral QCT (XCT 3000, Stratec)
      measurements were made in 53 individuals with CF and 53 controls. Bone mineral
      content (BMC), total volumetric BMD (vBMD) and cross sectional area (CSA) of the
      bone were measured at the 4% and 66% sites of the non-dominant tibia and radius.
      Additionally, trabecular vBMD and bone strength index (BSIc) were measured at the
      4% sites, and cortical vBMD, muscle CSA (mCSA) and strength strain index (SSI)
      were measured at the 66% sites. RESULTS: Pre-pubertal males with CF had greater
      trabecular vBMD (p=0.01) and total vBMD (p=0.00) at 4% tibia, and greater total
      vBMD (p=0.02) at 4% radius. Pre-pubertal females with CF had greater total vBMD
      at 66% tibia (p=0.02) and radius (p=0.04), and cortical vBMD (p=0.04) at the
      radius. At puberty, the CF cohort had less BMC at 4% tibia (males, p=0.02;
      females, p=0.01), and smaller mCSA at 66% tibia (males, p=0.02; females, p=0.01).
      Pubertal CF females had a smaller bone CSA (p=0.01) at 4% tibia, and lower bone
      strength (SSI) at the tibia (p=0.00) and radius (p=0.05) sites. CONCLUSIONS: Bone
      strength parameters were not compromised prior to puberty in this CF cohort. At
      puberty, the bone phenotype changed for this CF cohort, showing several deficits
      compared to the controls. However, bone strength was adapting to the mechanical
      demands of the muscle. Altered bone parameters and their implications for lowered
      bone strength with increased age may be greatly influenced by: the CF cohort
      remaining smaller for age and/or a reduced bone strain, secondary to reduced
      muscle force.

PMID- 25957708
TI  - Negative suction approach to remove living leeches from the nasal cavity.
AB  - OBJECTIVE: To explore a method for removing a living leech from the nasal cavity.
      MATERIALS AND METHODS: A total of 5 patients with nasal leech were examined.
      Nasal endoscopy revealed the presence of a wriggling leech in the nasal cavities
      of each of these patients. A negative suction tube with an inner diameter of 3 mm
      and a negative pressure of 30-40 kp was used to remove these leeches. In each
      case, this suction tube was aimed at the free end of the leech, and the leech was
      gradually and slowly sucked into the tube. The suckers of the removed leeches
      were examined to ensure that no leech fragments remained within each patient.
      RESULTS: In all 5 cases, the intact leech was successfully removed. No surgical
      complications occurred. CONCLUSIONS: The negative suction method can successfully
      remove nasal leeches.

PMID- 25957709
TI  - Leptin, adipocytes and breast cancer: Focus on inflammation and anti-tumor
      immunity.
AB  - More than one million new cases of breast cancer are diagnosed worldwide each
      year and more than 400,000 deaths are caused by the disease. The origin of this
      pathology is multifactorial and involved genetic, hormonal, environmental and
      nutritional factors including obesity in postmenopausal women. The role played by
      the adipose tissue and their secretions, ie adipokines, is beginning to be
      recognized. Plasma adipokine levels, which are modulated during obesity, could
      have "remote" effects on mammary carcinogenesis. Breast cancer cells are
      surrounded and locally influenced by an adipocyte microenvironment, which is
      probably more extensive in obese people. Hence, leptin appears to be strongly
      involved in mammary carcinogenesis and may contribute to the local pro
      inflammatory mechanisms, especially in obese patients, who have increased
      metastatic potential and greater risk of mortality. This review presents the
      multifaceted role of leptin in breast cancer development and the different
      molecular pathways involved such as inflammation, oxidative stress and antitumor
      immunity.

PMID- 25957710
TI  - Functional dynamics of claudin expression in Japanese medaka (Oryzias latipes):
      Response to environmental salinity.
AB  - Salinity regulation of 13 claudin paralogs was investigated in osmoregulatory
      organs of euryhaline Japanese medaka. They were identified by blast-search in the
      medaka genome database based on representation in osmoregulatory organs of other
      teleosts. Our hypothesis was that, because of their sequence similarities to
      mammalian orthologs previously characterized as barrier- and ion-selective
      channel-forming proteins, these paralogs would respond to salinity according to
      expected modulation of osmoregulatory function. Cldn10c, -10d, -10e, -10f, -27a, 
      28a, -28b and -30c had 4- to 100-fold higher expression in gill than other
      examined organs. Two splice variants of cldn10b were predominantly expressed in
      kidney, while cldn15a, -15b and -25 were found mainly in intestine. In gills,
      cldn27a, -28a, -28b and -30c did not change between fresh water (FW) and seawater
      (SW)-acclimated fish, while cldn10c, -10d, -10e, and -10f were most abundant in
      SW. Short-term SW transfer induced up-regulation of cldn10 gill paralogs after 1
      day, decrease in cldn28b and no difference for cldn27a, -28a and -30c. The
      reverse pattern was observed after FW transfer of SW medaka. Intestinal cldn15a
      and -25 did not differ between FW and SW fish. However, cldn15b was 10-fold
      higher in FW than SW, suggesting a role in functional modulation of the intestine
      related to water and salt transport. In kidney, cldn10bs were elevated in SW
      fish, suggesting a role in paracellular ion transport in the marine nephron.
      Based on in silico analysis, most gill Cldn10s were predicted to form cation
      pores, whereas Cldn27a, 28a, 28b and 30c may increase epithelial resistance.

PMID- 25957711
TI  - [Fungal infectivities of implanted catheters due to Candida sp. Biofilms
      formation and resistance].
AB  - BACKGROUND: Candidemia are the most common fungal infections in hospitals.
      However, the catheters are subject to be altered by Candida biofilms which
      increase the risk of invasive nosocomial infections due to the high resistance to
      antifungal agents. Therefore, the minimum inhibitory concentrations of planktonic
      (MIC) and sessile cells (CIMS) were evaluated. METHODS: To review the in vivo
      biofilms structures of Candida sp. formed on the inner and/or external surfaces
      of collected catheters, we used scanning electron microscopy (SEM). The level of
      biofilm resistance was assessed against two conventional antifungal agents:
      amphotericin B (AmB), which belongs to the class of polyenes, and fluconazole
      (FLZ) which is an azole. RESULTS: The SEM observation of biofilms of Candida sp.
      reveals complex structures. Compared to MICs, the calculation of CIMS showed an
      increase of 32 times with AmB and of 128 times with FLZ. CONCLUSION: Catheters
      offer an ideal surface to Candida sp. to form biofilms. This complex structure
      induces the increase of the resistance of sessile cells against two antifungal
      agents, AmB and FLZ.

PMID- 25957712
TI  - [Evaluation of mixed biofilm formation between Candida albicans and a variety of
      bacterial species isolated from peripheral catheters at Tlemcen CHU. First study
      in Algeria].
AB  - INTRODUCTION: Mixed-species biofilms constitute a reservoir of infection for a
      group of bacteria and yeasts that coexist on the same support. Peripheral venous
      catheters make up a good surface for the attachment of microorganisms that
      promote biofilm formation and this requires complex strategies for antimicrobial
      treatments. OBJECTIVE: No such studies on formation mixed biofilms have ever been
      conducted in Algeria. Therefore, we evaluated the potential for the formation of
      mixed-species biofilms by Candida albicans and some bacterial species isolated
      from peripheral vascular catheters at the University Hospital of Tlemcen, in
      Algeria. RESULTS: The results obtained showed that C. albicans have the potential
      to form mixed biofilms with three bacteria (Enterobacter cloacae, Bordetella spp.
      and Serratia liquefaciens) isolated from the same catheter as the yeasts. The
      amount of biofilms produced varies depending on the species and the composition
      of the growth medium. Observations by scanning electron microscopy showed that
      the structure of the mixed biofilm depends on the surface support the biofilm was
      formed on, and varies with the species. CONCLUSION: A competition was noted
      between bacteria and yeasts; it depends on the composition of the medium and its
      pH, which both play an important role in promoting the dominance of one over the
      other.

PMID- 25957713
TI  - Clinical utility of transperineal template-guided mapping biopsy of the prostate
      after negative magnetic resonance imaging-guided transrectal biopsy.
AB  - PURPOSE: We evaluated the prostate cancer detection with transperineal template
      guided mapping biopsy in patients with elevated prostate-specific antigen and
      negative magnetic resonance imaging (MRI)-guided biopsy. MATERIALS AND METHODS:
      Totally 75 patients underwent transperineal template-guided mapping biopsy for
      prior negative MRI-guided (cognitive registration) biopsy during April 2013 to
      August 2014. Primary objective was to report clinically significant cancer
      detection in this cohort of patients. Significant cancer was defined using
      varying thresholds of MCL or Gleason grade 3+4 or greater or both. Cancers with
      more than 80% of positive core length anterior to the level of urethra were
      termed anterior zone cancer. Secondary objective was to evaluate the potential
      clinical and radiological predictors for significant cancer detection. RESULTS:
      The mean age was 61.6 +/- 6.5 years and median prostate-specific antigen was 10.4
      ng/dl (7.9-18) with a mean MRI target size of 7.2mm (4-11). Transperineal
      template-guided mapping biopsy identified cancer in 36% (27/75) patients and
      66.6% (18/27) of them were anterior zone cancers. The rates of detection of
      clinically significant and insignificant cancer according to the several
      definitions used range from 22.7% to 30.7% and 5.3% to 13.3%, respectively.
      Multivariate analysis did not identify any predictors for finding clinically
      significant and anterior cancers in this group of patients. CONCLUSION:
      Transperineal template-guided mapping biopsy appears to be an excellent biopsy
      protocol for downstream management following negative MRI-guided biopsy. Most of
      the cancers detected were predominantly anterior tumors.

PMID- 25957715
TI  - Toxicity of naphthenic acid fraction components extracted from fresh and aged oil
      sands process-affected waters, and commercial naphthenic acid mixtures, to
      fathead minnow (Pimephales promelas) embryos.
AB  - Naphthenic acids (NAs) are constituents of oil sands process-affected water
      (OSPW). These compounds can be both toxic and persistent and thus are a primary
      concern for the ultimate remediation of tailings ponds in northern Alberta's oil
      sands regions. Recent research has focused on the toxicity of NAs to the highly
      vulnerable early life-stages of fish. Here we examined fathead minnow embryonic
      survival, growth and deformities after exposure to extracted NA fraction
      components (NAFCs), from fresh and aged oil sands process-affected water (OSPW),
      as well as commercially available NA mixtures. Commercial NA mixtures were
      dominated by acyclic O2 species, while NAFCs from OSPW were dominated by bi- and
      tricyclic O2 species. Fathead minnow embryos less than 24h old were reared in
      tissue culture plates terminating at hatch. Both NAFC and commercial NA mixtures
      reduced hatch success, although NAFCs from OSPW were less toxic (EC50=5-12mg/L,
      nominal concentrations) than commercial NAs (2mg/L, nominal concentrations). The
      toxicities of NAFCs from aged and fresh OSPW were similar. Embryonic heart rates
      at 2 days post-fertilization (dpf) declined with increasing NAFC exposure,
      paralleling patterns of hatch success and rates of cardiovascular abnormalities
      (e.g., pericardial edemas) at hatch. Finfold deformities increased in exposures
      to commercial NA mixtures, not NAFCs. Thus, commercial NA mixtures are not
      appropriate surrogates for NAFC toxicity. Further work clarifying the mechanisms
      of action of NAFCs in OSPW, as well as comparisons with additional aged sources
      of OSPW, is merited. 

PMID- 25957714
TI  - Chemotherapy and radiotherapy in nasopharyngeal carcinoma: an update of the MAC
      NPC meta-analysis.
AB  - BACKGROUND: A previous individual patient data meta-analysis by the Meta-Analysis
      of Chemotherapy in Nasopharynx Carcinoma (MAC-NPC) collaborative group to assess
      the addition of chemotherapy to radiotherapy showed that it improves overall
      survival in nasopharyngeal carcinoma. This benefit was restricted to patients
      receiving concomitant chemotherapy and radiotherapy. The aim of this study was to
      update the meta-analysis, include recent trials, and to analyse separately the
      benefit of concomitant plus adjuvant chemotherapy. METHODS: We searched PubMed,
      Web of Science, Cochrane Controlled Trials meta-register, ClinicalTrials.gov, and
      meeting proceedings to identify published or unpublished randomised trials
      assessing radiotherapy with or without chemotherapy in patients with non
      metastatic nasopharyngeal carcinoma and obtained updated data for previously
      analysed studies. The primary endpoint of interest was overall survival. All
      trial results were combined and analysed using a fixed-effects model. The
      statistical analysis plan was pre-specified in a protocol. All data were analysed
      on an intention-to-treat basis. FINDINGS: We analysed data from 19 trials and
      4806 patients. Median follow-up was 7.7 years (IQR 6.2-11.9). We found that the
      addition of chemotherapy to radiotherapy significantly improved overall survival
      (hazard ratio [HR] 0.79, 95% CI 0.73-0.86, p<0.0001; absolute benefit at 5 years
      6.3%, 95% CI 3.5-9.1). The interaction between treatment effect (benefit of
      chemotherapy) on overall survival and the timing of chemotherapy was significant
      (p=0.01) in favour of concomitant plus adjuvant chemotherapy (HR 0.65, 0.56-0.76)
      and concomitant without adjuvant chemotherapy (0.80, 0.70-0.93) but not adjuvant
      chemotherapy alone (0.87, 0.68-1.12) or induction chemotherapy alone (0.96, 0.80
      1.16). The benefit of the addition of chemotherapy was consistent for all
      endpoints analysed (all p<0.0001): progression-free survival (HR 0.75, 95% CI
      0.69-0.81), locoregional control (0.73, 0.64-0.83), distant control (0.67, 0.59
      0.75), and cancer mortality (0.76, 0.69-0.84). INTERPRETATION: Our results
      confirm that the addition of concomitant chemotherapy to radiotherapy
      significantly improves survival in patients with locoregionally advanced
      nasopharyngeal carcinoma. To our knowledge, this is the first analysis that
      examines the effect of concomitant chemotherapy with and without adjuvant
      chemotherapy as distinct groups. Further studies on the specific benefits of
      adjuvant chemotherapy after concomitant chemoradiotherapy are needed. FUNDING:
      French Ministry of Health (Programme d'actions integrees de recherche VADS),
      Ligue Nationale Contre le Cancer, and Sanofi-Aventis.

PMID- 25957716
TI  - Investigation of olive mill wastewater (OMW) ozonation efficiency with the use of
      a battery of selected ecotoxicity and human toxicity assays.
AB  - The effects of olive mill wastewater (OMW) on a battery of biological assays,
      before and during the ozonation process, were investigated in order to assess
      ozone's efficiency in removing phenolic compounds from OMW and decreasing the
      concomitant OMW toxicity. Specifically, ozonated-OMW held for 0, 60, 120, 300,
      420, 540min in a glass bubble reactor, showed a drastic reduction of OMW total
      phenols (almost 50%) after 300min of ozonation with a concomitant decrease of OMW
      toxicity. In particular, the acute toxicity test primarily performed in the fairy
      shrimp Thamnocephalus platyurus (Thamnotoxkit FTM screening toxicity test) showed
      a significant attenuation of OMW-induced toxic effects, after ozonation for a
      period of 120 and in a lesser extent 300min, while further treatment resulted in
      a significant enhancement of ozonated-OMW toxic effects. Furthermore, ozonated
      OMW-treated mussel hemocytes showed a significant attenuation of the ability of
      OMW to cause cytotoxic (obtained by the use of NRRT assay) effects already after
      an ozonation period of 120 and to a lesser extent 300min. In accordance with the
      latter, OMW-mediated oxidative (enhanced levels of superoxide anions and lipid
      peroxidation by-products) and genotoxic (induction of DNA damage) effects were
      diminished after OMW ozonation for the aforementioned periods of time. The latter
      was also revealed by the use of cytokinesis block micronucleus (CBMN) assay in
      human lymphocytes exposed to different concentrations of both raw- and ozonated
      OMW for 60, 120 and 300min. Those findings revealed for a first time the
      existence of a critical time point during the OMW ozonation process that could be
      fundamentally used for evaluating OMW ozonation as a pretreatment method of OMW. 

PMID- 25957717
TI  - Presenting symptoms of GBA-related Parkinson's disease.
AB  - BACKGROUND: Mutations in the Glucocerebrosidase gene (GBA) are associated with
      Parkinson's disease (PD). It has been shown that GBA-related PD (PD-GBA) patients
      had an earlier age at PD onset and more prevalent non-motor symptoms when
      compared to "sporadic" PD patients without such mutations (sPD). AIM: To explore
      whether presenting symptoms differ between PD-GBA and sPD patients. METHODS:
      Demographic and clinical features (including presenting symptoms) were collected
      for 578 PD patients. Sequence analysis was performed for exons 8-11 of the GBA
      gene for all participants. RESULTS: 39 PD patients (6.7%) with GBA mutations were
      compared to 539 PD patients without them. Although no statistically significant
      differences were found regarding the presenting symptoms, we observed that pain
      was more frequently reported as an initial problem in the PD-GBA (10.3%) than in
      the sPD group (3.0%) (chi square p = 0.039; logistic regression analysis OR =
      3.74; p = 0.024). CONCLUSIONS: Overall, the presenting symptoms were similar in
      PD-GBA and sPD patients, with the exception that pain might be more frequent in
      PD-GBA.

PMID- 25957718
TI  - Immobilization of nitrate reductase onto epoxy affixed silver nanoparticles for
      determination of soil nitrates.
AB  - Epoxy glued silver nanoparticles were used as immobilization support for nitrate
      reductase (NR). The resulting epoxy/AgNPs/NR conjugates were characterized at
      successive stages of fabrication by scanning electron microscopy and fourier
      transform infrared spectroscopy. The immobilized enzyme system exhibited
      reasonably high conjugation yield (37.6+/-0.01 MUg/cm(2)), with 93.54+/-0.88%
      retention of specific activity. Most favorable working conditions of pH,
      temperature and substrate concentration were ascertained to optimize the
      performance of epoxy/AgNPs/NR conjugates for soil nitrate quantification. The
      analytical results for soil nitrate determination were consistent, reliable and
      reproducible. Minimum detection limit of the method was 0.05 mM with linearity
      from 0.1 to 11.0 mM. The % recoveries of added nitrates (0.1 and 0.2 mM)
      were<95.0% and within-day and between-day coefficients of variations were 0.556%
      and 1.63% respectively. The method showed good correlation (R(2)=0.998) with the
      popular Griess reaction method. Epoxy/AgNPs bound NR had a half-life of 18 days
      at 4  degrees C and retained 50% activity after 15 reuses.

PMID- 25957719
TI  - An indigenous Halomonas BVR1 strain immobilized in crosslinked chitosan for
      adsorption of lead and cadmium.
AB  - Biomacromolecules play an important role in the adsorption of metals. In this
      context, we have studied the potential of an indigenous Halomonas BVR1 strain
      (isolated from an electronic industry effluent) immobilized in a glutaraldehyde
      crosslinked chitosan matrix for the adsorption of lead and cadmium. Adequate
      physico-chemical characterizations and the study of thermodynamic and kinetic
      parameters authenticated the experimental observations and the interaction
      mechanism. The adsorption was facile in the pH range 5-7 and pseudo second order
      kinetic model was favourable for both the metals. The Langmuir adsorption
      capacities for lead and cadmium were found to be 24.15 mg g(-1) and 23.88 mg g(
      1) respectively. The negative DeltaG values confirmed the thermodynamic
      feasibility and this lucid approach highlights the utility of green methodology
      for heavy metal adsorption.

PMID- 25957720
TI  - Nitric oxide-releasing chitosan film for enhanced antibacterial and in vivo wound
      healing efficacy.
AB  - Nitric oxide (NO) is a promising therapeutic agent with antibacterial and wound
      healing properties. However, the gaseous state and short half-life of NO
      necessitate a formulation that can control its storage and release. In this
      study, we developed NO-releasing films (CS/NO film) composed of chitosan (CS) and
      S-nitrosoglutathione (GSNO) as a NO donor. Thermal analysis demonstrated
      molecular dispersion of GSNO in the films. In vitro release study revealed that
      NO release from CS/NO films followed Korsmeyer-Peppas model with Fickian
      diffusion kinetics. Moreover, the CS/NO film showed a stronger antibacterial
      activity against Pseudomonas aeruginosa (Gram-negative) and Staphylococcus aureus
      (Gram-positive) than the CS film. Further, the CS/NO film accelerated wound
      healing and epithelialization in a rat model of full-thickness wounds as compared
      to the CS film. Histopathological studies revealed that CS/NO films favorably
      enhanced the re-epithelialization and reconstruction of wounded skin. Therefore,
      our results suggest that CS/NO films could be a suitable formulation for treating
      full-thickness wounds. 

PMID- 25957721
TI  - Sulfated modification, characterization and property of a water-insoluble
      polysaccharide from Ganoderma atrum.
AB  - Sulfated modification was carried out to modify a water-insoluble polysaccharide
      from Ganoderma atrum (AGAP). The effects of sulfation on structure,
      physicochemical and functional properties of AGAP were investigated. Three
      sulfated derivatives were prepared, designated as S-1, S-2 and S-3 with degree of
      substitution (DS) of 0.35, 0.74 and 1.14, respectively. AGAP was elucidated as an
      alpha-(1->3)-glucan with few branches terminated by single mannose or xylose
      residues. The molecular weight (Mw) and radius of gyration (Rg) were estimated to
      be 1665 kDa and 65.49 nm, respectively. After sulfated modification, non
      selective sulfation occurred preferably at O-6, partially at O-2 and O-4
      positions of the glucosyl residues. The water-solubility of the derivatives was
      significantly improved in a DS-dependent manner. Mw of the derivatives showed a
      sharp decrease, and the chain conformation was estimated to be expanded stiff in
      phosphate buffer. In vitro tests showed that sulfated modification improved its
      antioxidant activities and anti-proliferative ability against S-180 tumor cells.
      This study suggested that sulfated modification was an effective approach to
      improve the water-solubility and functional properties of insoluble
      polysaccharides.

PMID- 25957723
TI  - Functional Neuronavigation-Guided Transparieto-Occipital Cortical Resection of
      Meningiomas in Trigone of Lateral Ventricle.
AB  - BACKGROUND: This study investigated whether functional neuronavigation can be
      used to remove lesions in the lateral ventricle while preserving patients'
      neurologic functionality. METHODS: A total of 60 patients with lateral
      ventricular meningiomas were divided into study and control groups (n = 30 each).
      Diffusion tensor and blood oxygenation level-dependent functional magnetic
      resonance imaging were used for fiber tracking and eloquent cortex localization,
      respectively, in the study group. The surgical approach was based on coregistered
      data sets from 3-D lesion and brain structure reconstructions. Patients in the
      control group underwent anatomic neuronavigation-guided surgery. The patients'
      demographics, degree of resection, visual field, language score, movement,
      preoperative and postoperative Karnofsky Performance Status (KPS) scores, and
      surgical complications were recorded. RESULTS: Tumors were completely removed in
      both groups. Patients in the study group had a higher rate of visual field
      preservation than controls (P = 0.01). The two groups had similar motor and
      language functions after surgery, except that fewer cases of transient aphasia
      were observed in the former (P < 0.05). KPS scores for the study and control
      groups were 80 (70-80) and 70 (60-70), respectively (P < 0.01), at 2 weeks and 90
      (80-100) and 85 (70-90), respectively (P = 0.022), at 3 months after surgery.
      CONCLUSIONS: Functional neuronavigation preserved neurologic functionality and
      was especially beneficial for protecting optical functionality and for the rapid
      recovery of patients.

PMID- 25957722
TI  - Validity of the Lateral Supraorbital Approach as a Minimally Invasive Corridor
      for Orbital Lesions.
AB  - BACKGROUND: Many approaches were recommended for surgical treatment of orbital
      lesions via either transorbital or transcranial routes. The frontolateral
      craniotomy through eyebrow skin incision (lateral supraorbital approach) is a
      combined cranio-orbital approach that could be used in different orbital lesions.
      OBJECTIVES: To evaluate the efficacy and safety of the lateral supraorbital
      approach for resection of orbital lesions. PATIENTS AND METHODS: Ten patients
      with different orbital lesions were treated by this minimally invasive technique.
      The technique is described in details. The postoperative outcome was evaluated
      with casting light on the specific parameters related to this approach. RESULTS:
      This study included 6 females and 4 males, ranging in age from 2 years to 65
      years with mean age of 37.3 years. Proptosis was the most common presenting
      complaint. Six patients were operated on via the right supraorbital approach, and
      4 patients via the left supraorbital approach. Various pathological lesions were
      treated. The excision was total in 7 patients, subtotal in 1 patient, and partial
      in 2 patients. Two patients suffered transient supraorbital hypothesia, 1 patient
      showed temporary superficial wound infection with CSF leak and 1 patient died
      within 6 months. CONCLUSION: The lateral supraorbital approach is a minimally
      invasive approach that provides excellent exposure of the superior, lateral, and
      medial orbit, as well as the orbital apex.

PMID- 25957724
TI  - Open Transcranial Resection of Small (<35 mm) Meningiomas of the Anterior Midline
      Skull Base in Current Microsurgical Practice.
AB  - OBJECTIVE: Despite technical surgical advance, the ultimate management of midline
      anterior skull base meningiomas remains to be defined. Open transcranial surgery
      is usually the first treatment option for large meningiomas, while less invasive
      techniques such as endoscopic surgery or radiosurgery might represent an
      alternative to open microsurgery for smaller lesions. The aim of our study is to
      investigate the outcome of open transcranial microsurgery in the resection of
      small (<35 mm) meningiomas of the midline anterior cranial base. METHODS:
      Clinical and surgical data from 43 patients affected by small midline anterior
      skull base meningiomas operated via an open transcranial approach were
      retrospectively reviewed. RESULTS: The tumor diameter on its major axis ranged
      from 12 to 35 mm, with a mean diameter of 28 mm. Gross total resection (Simpson
      grades I-II) was achieved in 100% of cases through a pterional approach.
      Postoperative overall morbidity was 9%. It was 3% among patients <70 years. No
      mortality was reported. Postoperative visual outcome was significantly associated
      with preoperative visual performance (P = 0.02), but not with preoperative optic
      nerve compression as detected by magnetic resonance imaging (P = 0.116). Age >70
      years was associated with postoperative visual impairment, although not
      significantly (P = 0.06). Visual function was preserved or improved in 95% of
      cases, in 100% of patients <70 years, and in 71% of patients with preoperative
      visual impairment. CONCLUSIONS: In our experience, open transcranial surgery
      proved safe and effective for midline anterior skull base meningiomas smaller
      than 35 mm in all patients <70 years and in patients >70 years without
      preoperative visual deficit. Our data are consistent with the literature.
      Conversely, the standard of treatment for the subgroup of patients >70 years with
      preoperative visual deficit has not yet been defined. This specific subgroup of
      patients offers a topic for further investigation.

PMID- 25957725
TI  - Simulation Training Curricula for Neurosurgical Residents: Cervical Foraminotomy
      and Durotomy Repair Modules.
AB  - INTRODUCTION: Since 2010, the Congress of Neurological Surgeons (CNS) has offered
      a neurosurgical skills simulation course for residents and medical students. The
      authors describe their experience with incorporation of two neurosurgical skills
      simulation modules into the dedicated resident training curriculum of a single
      ACGME-accredited training program, using lumbar dural repair (5) and posterior
      cervical laminoforaminotomy modules from the CNS simulation initiative (6).
      METHODS: Each of the available 22 neurosurgery residents at a single residency
      program was given two 20-question pretests for a cervical laminoforaminotomy and
      durotomy repair module as a basic test of regional anatomy, general disease
      knowledge, surgical decision making, and recently published literature. This was
      followed by a faculty-directed skills simulation course and concluded with a
      final 20 question post-test. RESULTS: Posterior cervical laminoforaminotomy was
      performed once by each resident, and grading was conducted using the
      predetermined OSATs. The overall score was 56.1 (70%, range 26-76, maximum 80
      points) with a trend towards higher scores with advanced levels of training. All
      residents completed the durotomy repair OSATs for a total of three trials. Of a
      maximum composite score of 60, a mean 37.2 (62%, range 15-58) was scored by the
      residents (Table 3). The mean OSAT scores for each durotomy trial was 2.66, 3.15,
      and 3.48 on each success test. A trend towards higher scores in advanced years of
      training was observed, but did not reach statistical significance (Figure 3).
      CONCLUSIONS: Duty hour limitations and regulatory pressure for enhanced quality
      and outcomes may limit access of neurosurgical residents to fundamental skills
      training. Fundamental skills training as part of a validated simulation
      curriculum can mitigate this challenge to residency education. National
      development of effective technical simulation modules for use in individual
      residency training programs is a promising strategy to achieve these goals.

PMID- 25957726
TI  - Acute Brain Injury after Subarachnoid Hemorrhage.

PMID- 25957727
TI  - Looking Beyond the Surface of Adult Moyamoya Disease: Brain Magnetic Resonance
      Imaging Microstructural Changes and Cognitive Dysfunction.

PMID- 25957728
TI  - Primary Endoscopic Transnasal Transsphenoidal Surgery for Magnetic Resonance
      Image-Positive Cushing Disease: Outcomes of a Series over 14 Years.
AB  - BACKGROUND: There are scant data of endoscopic transsphenoidal surgery (ETS) with
      adjuvant therapies of Cushing disease (CD). OBJECTIVE: To report the remission
      rate, secondary management, and outcomes of a series of CD patients. METHODS:
      Patients with CD with magnetic resonance imaging (MRI)-positive adenoma who
      underwent ETS as the first and primary treatment were included. The diagnostic
      criteria were a combination of 24-hour urine-free cortisol, elevated serum
      cortisol levels, or other tests (e.g., inferior petrosal sinus sampling). All
      clinical and laboratory evaluations and radiological examinations were reviewed.
      RESULTS: Forty consecutive CD patients, with an average age of 41.0 years, were
      analyzed with a mean follow-up of 40.2 +/- 29.6 months. These included 22
      patients with microadenoma and 18 with macroadenoma, including 9 cavernous
      invasions. The overall remission rate of CD after ETS was 72.5% throughout the
      entire follow-up. Patients with microadenoma or noninvasive macroadenoma had a
      higher remission rate than those who had macroadenoma with cavernous sinus
      invasion (81.8% or 77.8% vs. 44.4%, P = 0.02). After ETS, the patients who had
      adrenocorticotropic hormone-positive adenoma had a higher remission rate than
      those who had not (76.5% vs. 50%, P = 0.03). In the 11 patients who had
      persistent/recurrent CD after the first ETS, 1 underwent secondary ETS, 8
      received gamma-knife radiosurgery (GKRS), and 2 underwent both. At the study end
      point, two (5%) of these CD patients had persistent CD and were under the
      medication of ketoconazole. CONCLUSION: For MRI-positive CD patients, primary
      (i.e., the first) ETS yielded an overall remission rate of 72.5%. Adjuvant
      therapies, including secondary ETS, GKRS, or both, yielded an ultimate remission
      rate of 95%.

PMID- 25957729
TI  - Cancer Etiology, Bad Luck, and Ecological Fallacy.

PMID- 25957730
TI  - Antiplatelets Versus Anticoagulation for Cervical Arterial Dissection.

PMID- 25957731
TI  - Prevalence of behavioural risk factors for cardiovascular disease in adolescents
      in low-income and middle-income countries: an individual participant data meta
      analysis.
AB  - BACKGROUND: Although overt manifestations of cardiovascular disease (CVD) rarely
      emerge before adulthood, CVD risk factors are often present in adolescents.
      However, the prevalence and magnitude of behavioural CVD risk factors in
      adolescents in low-income and middle-income countries remains unclear. We
      estimated the magnitude and co-occurrence of behavioural CVD risk factors in
      adolescents aged 12-15 years for 65 low-income and middle-income countries
      between 2003 and 2011. METHODS: We extracted Global School-Based Student Health
      Surveys (GSHS) datasets from the Centers for Disease Control and Prevention (CDC)
      website. Pooled prevalence estimates of current tobacco use, alcohol use, low
      fruit and vegetable intake, low physical activity, obesity and co-occurrence of
      CVD risk factors for WHO regions and overall, was calculated with random-effects
      meta-analysis. We explored potential sources of heterogeneity for each CVD risk
      factor through random-effects meta-regression analysis. FINDINGS: Between 2003
      and 2011, of 169 369 adolescents, 12.1% (95% CI 10.2-14.1) used tobacco, 15.7%
      (12.3-19.5) used alcohol, 74.3% (71.9 -76.5) had low fruit and vegetable intake,
      71.4% (69.5-73.3) reported low physical activity and 7.1% (5.6-8.7) were obese.
      The pooled regional prevalence of exposure to three or more CVD risk factors was
      lowest in the southeast Asian region (3.8%, 95% CI 1.2-7.5) and highest in the
      western Pacific region (18.6%, 12.8-25.3). Substantial heterogeneities within and
      across regions were not fully explained by major study characteristics.
      INTERPRETATION: In low-income and middle-income countries, adolescents carry a
      substantial burden of behavioural CVD risk factors, which tend to co-occur.
      Surveillance, prevention, detection, and control initiatives are a global health
      priority. FUNDING: None.

PMID- 25957732
TI  - Cardiovascular health promotion in adolescents: a vital investment.

PMID- 25957734
TI  - Optimal ADF STEM imaging parameters for tilt-robust image quantification.
AB  - An approach towards experiment design and optimisation is proposed for achieving
      improved accuracy of ADF STEM quantification. In particular, improved robustness
      to small sample mis-tilts can be achieved by optimising detector collection and
      probe convergence angles. A decrease in cross section is seen for tilted samples
      due to the reduction in channelling, resulting in a quantification error, if this
      is not taken into account. At a smaller detector collection angle the increased
      contribution from elastic scattering, which initially increases with tilt, can be
      used to offset the decrease in the TDS signal. 

PMID- 25957733
TI  - The influence of zinc chloride and zinc oxide nanoparticles on air-time survival
      in freshwater mussels.
AB  - The purpose of this study was to determine the cumulative effects of exposure to
      either dissolved zinc or nanozinc oxide (nanoZnO) and air-time survival in
      freshwater mussels. Mussels were exposed to each forms of zinc for 96h then
      placed in air to determine survival time. A sub-group of mussels before and after
      7days of exposure to air were kept aside for the determination of the following
      biomarkers: arachidonate-dependent cyclooxygenase (COX) and peroxidase
      (inflammation and oxidative stress), lipid metabolism (total lipids, esterases
      activity, HO-glycerol, acetyl CoA and phospholipase A2) and lipid damage (lipid
      peroxidation [LPO]). The results showed that air-time survival was decreased from
      a mean value of 18.5days to a mean value of 12days in mussels exposed to 2.5mg/L
      of nanoZnO although it was not lethal based on shell opening at concentrations
      below 50mg/L after 96h. In mussels exposed to zinc only, the median lethal
      concentration was estimated at 16mg/L (10-25 95% CI). The air-time survival did
      not significantly change in mussels exposed to the same concentration of
      dissolved Zn. Significant weight losses were observed at 0.5mg/L of nanoZnO and
      at 2.5mg/L for dissolved zinc chloride, and were also significantly correlated
      with air-time survival (r=0.53; p<0.01). Air exposure significantly increased COX
      activity in control mussels and in mussels exposed to 0.5mg/L of nanoZnO and zinc
      chloride. The data also suggested fatty acid breakdown and beta-oxidation.
      Mussels exposed to contaminants are more susceptible to prolonged exposure to air
      during low water levels. 

PMID- 25957735
TI  - Editorial: Care of adults with Down syndrome: Gaps and needs.

PMID- 25957736
TI  - Laparoscopic cholecystectomy in elderly patients: an evaluation of immunity.
AB  - OBJECTIVE: We sought to investigate the impact of laparoscopic cholecystectomy
      (LC) on the inflammatory response and immunological function of elderly patients
      compared with that on the younger ones. METHODS: Between June 2012 and June 2013,
      this prospective study investigated a total of 112 patients having the surgery of
      LC due to symptomatic cholelithiasis or polyps, among whom 52 were elderly
      patients with the age beyond 65 years old and the remaining 60 were younger than
      the age. Peripheral venous blood samples were taken from these patients prior to
      surgery and on post-operative days 1, 3 and 7, respectively. The perioperative
      clinical outcomes and immunological function results were analyzed and compared
      between the two groups divided by age. RESULTS: The demographics of the two
      groups did not differ except for the age. Surgical trauma seemed more serious for
      elderly patients as illustrated by the longer operating time, hospital stay and
      more quantity of patients got complication. Both groups indicated changes in
      inflammatory and immune aspects. Compared with the younger ones, elderly patients
      showed less quantity of preoperative basic immune cells, delayed immune responses
      after the surgical trauma of LC and hyporeactivity of inflammatory response when
      accepting LC. CONCLUSIONS: An examination of the inflammatory reaction and immune
      response after LC demonstrated that there are significant differences observed in
      two groups divided by age. Further studies with more samples are required to
      determine the exact relationship of perioperative immune change and higher
      adverse outcome rate of aged people.

PMID- 25957737
TI  - The impact of incontinence management on informal caregivers' quality of life.
AB  - BACKGROUND: The presence of incontinence symptoms might affect the quality of
      life (QoL) of those providing informal care to people suffering from them,
      causing social isolation, financial problems, psychological and physical
      exhaustion. AIMS: This study aimed at assessing whether urinary and/or fecal
      incontinence in people aged 60 and over affects the level of burden in their
      informal caregivers. METHODS: QoL was assessed amongst 304 informal caregivers of
      older people suffering from urinary and/or fecal incontinence, and compared to
      that reported by 305 caregivers of non-incontinent older relatives, all living in
      Italy. All participants were administered a questionnaire focused on:
      characteristics and conditions of the cared for; details of the care activity;
      emotions experienced by caregivers; attitudes of caregivers; reasons for
      providing care; availability of information and support; demographics. RESULTS:
      Findings show that, when no incontinence was reported, the longer was the
      caregiving situation, the better was the caregivers' QoL, which was instead
      negatively affected by the lack of a support network. As for caregivers'
      feelings, neither positive nor negative emotions influenced their QoL in a
      significant way. In terms of caregiver's role, those who felt overwhelmed or
      loaded with responsibility reported a lower QoL, while the opposite was found
      among those who felt rewarded and supported, even when incontinence-of any kind
      was present. CONCLUSIONS: The management of incontinence does have a negative
      impact on caregivers' QoL, but subjective factors might play a mitigating role on
      such an impact.

PMID- 25957738
TI  - Lazaroid U-74389G inhibits the osteoblastic differentiation of IL-1beta-indcued
      aortic valve interstitial cells through glucocorticoid receptor and inhibition of
      NF-kappaB pathway.
AB  - BACKGROUND: Aortic valve calcification is characterized as the active process of
      aortic valve interstitial cells (AVICs), and considered as an inflammatory
      disease. As an antioxidant, the anti-inflammatory activity of Lazaroid has been
      exhibited in various models. We hypothesized that Lazaroid U-74389G would inhibit
      the osteoblastic differentiation of AVICs induced by IL-1beta. METHODS: Normal
      tricuspid aortic valve leaflets were collected from patients with acute aortic
      dissection (Type A) undergoing the Bentall procedure. AVICs were isolated and
      stimulated with IL-1beta in presence or absence of U-74389G in culture. Cell
      lysates were analyzed for osteogenic markers and nuclear factor-kappaB using real
      time PCR and Immunoblotting. Culture media was analyzed for IL-6 and IL-8 with
      enzyme-linked immunosorbent assay. Alizarin Red Staining was adopted to
      demonstrate the calcium deposition. RESULTS: The expression of alkaline
      phosphatase and bone morphogenetic protein, accompanied by the production of IL-6
      and IL-8, was up-regulated in response to IL-1beta and was inhibited by the
      addition of U-74389G. The NF-kappaB pathway was activated by IL-1beta and
      involved in the suppression of U-74389G on osteoblastic differentiation in AVICs.
      The negative effects of U-74389G on ostengenic gene expression and mineralization
      of AVICs were blocked by glucocorticoid receptor antagonist mifepristone and the
      NF-kappaB inhibitor Bay 11-7082. CONCLUSIONS: U-74389G inhibits the pro
      osteogenic response to IL-1beta stimulation in AVICs. The osteoblastic
      differentiation and mineralization of AVICs were inhabited by U-74389G though the
      modulation of NF-kappaB activation, and this pathway could be potential
      therapeutic targets for medical treatment of calcified aortic valve disease.

PMID- 25957740
TI  - Equivalent Survival With Mastectomy or Breast-conserving Surgery Plus Radiation
      in Young Women Aged < 40 Years With Early-Stage Breast Cancer: A National
      Registry-based Stage-by-Stage Comparison.
AB  - BACKGROUND: Studies have shown that young patients with early-stage breast cancer
      (BC) are increasingly undergoing mastectomy instead of breast-conserving therapy
      (BCT) consisting of lumpectomy and radiation. We examined the difference in
      outcomes in young women (aged < 40 years) who had undergone BCT versus
      mastectomy. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End
      Results database was queried for women aged < 40 years with stage I or II
      invasive BC treated with surgery from 1998 to 2003. Breast cancer-specific
      survival (BCSS) and overall survival (OS) were evaluated using Kaplan-Meier
      survival analysis and the log-rank test between treatment types. RESULTS: Of the
      7665 women, 3249 received BCT and 2627 underwent mastectomy without radiation.
      When separated by stage (I, IIA, and IIB), with a median follow-up duration of
      111 months, the BCT and mastectomy-only groups showed no statistically
      significant differences in BCSS and OS. Overall, the age group of 35 to 39 years
      (66% of total) was associated with better 10-year BCSS (88%) and OS (86.1%)
      compared with the younger patients aged 20 to 34 years (34% of total). The latter
      group had a 10-year BCSS and OS of 84.1% and 82.3%, respectively (P < .001 for
      both BCSS and OS). However, when the patients of each age group were further
      subdivided by stage, the BCT group continued to show noninferior BCSS and OS
      compared with the mastectomy group in all subgroups. CONCLUSION: The results of
      our study suggest that although young age might be a poor prognostic factor for
      BC, no evidence has shown that these patients will have better outcomes after
      mastectomy than after BCT.

PMID- 25957741
TI  - Quercetin protects mouse liver against nickel-induced DNA methylation and
      inflammation associated with the Nrf2/HO-1 and p38/STAT1/NF-kappaB pathway.
AB  - Quercetin (QE), a natural flavonoid, has been reported to have many benefits and
      medicinal properties. However, its protective effects against nickel (Ni) induced
      injury in liver have not been clarified. The aim of the present study was to
      investigate the effects of quercetin on hepatic DNA methylation and inflammation
      in mice exposed to nickel. ICR mice were exposed to nickel sulfate with or
      without quercetin co-administration for 20 days. Our results showed that
      quercetin administration significantly inhibited nickel-induced liver injury,
      which was indicated by diagnostic indicators. In exploring the underlying
      mechanisms of quercetin action, we found that quercetin decreased total DNA
      methyltransferases (DNMTs) activity and DNA methylation level of the NF-E2
      related factor 2 (Nrf2) DNA in livers of nickel-treated mice. Quercetin also
      induced Nrf2 nuclear translocation and heme oxygenase-1 (HO-1) activity.
      Moreover, quercetin decreased production of pro-inflammatory markers including
      TNF-alpha, IL-1beta and iNOS. Quercetin significantly inhibited the p38 and
      signal transducer and activator of transcription 1 (STAT1) activation, which in
      turn inactivated NF-kappaB and the inflammatory cytokines in livers of the nickel
      treated mice. In conclusion, these results suggested that the inhibition of
      nickel-induced inflammation by quercetin is associated with its ability to
      modulate Nrf2/HO-1 and p38/STAT1/NF-kappaB signaling pathway. 

PMID- 25957739
TI  - Prognostic Modeling in Pathologic N1 Breast Cancer Without Elective Nodal
      Irradiation After Current Standard Systemic Management.
AB  - OBJECTIVE: This study was conducted to establish a prognostic model in patients
      with pathologic N1 (pN1) breast cancer who have not undergone elective nodal
      irradiation (ENI) under the current standard management and to suggest possible
      indications for ENI. METHODS: We performed a retrospective study with patients
      with pN1 breast cancer who received the standard local and preferred adjuvant
      chemotherapy treatment without neoadjuvant chemotherapy and ENI from January 2005
      to June 2011. Most of the indicated patients received endocrine and trastuzumab
      therapy. RESULTS: In 735 enrolled patients, the median follow-up period was 58.4
      months (range, 7.2-111.3 months). Overall, 55 recurrences (7.4%) developed, and
      locoregional recurrence was present in 27 patients (3.8%). Recurrence-free
      survival was significantly related to lymphovascular invasion (P = .04, hazard
      ratio [HR], 1.83; 95% confidence interval [CI], 1.03-2.88), histologic grade (P =
      .03, HR, 2.57; 95% CI, 1.05-6.26), and nonluminal A subtype (P = .02, HR, 3.04;
      95% CI, 1.23-7.49) in multivariate analysis. The prognostic model was established
      by these 3 prognostic factors. Recurrence-free survival was less than 90% at 5
      years in cases with 2 or 3 factors. CONCLUSIONS: The prognostic model has
      stratified risk groups in pN1 breast cancer without ENI. Patients with 2 or more
      factors should be considered for ENI.

PMID- 25957742
TI  - The protective role of olive oil hydroxytyrosol against oxidative alterations
      induced by mercury in human erythrocytes.
AB  - Hydroxytyrosol (HT) is a phenolic antioxidant naturally occurring in virgin olive
      oil. In this study, we investigated the possible protective effects of HT on the
      oxidative and morphological alterations induced by mercury (Hg) in intact human
      erythrocytes. These cells preferentially accumulate this toxic heavy metal. More
      importantly, Hg-induced echinocyte formation correlates with increased
      coagulability of these cells. Our results indicate that HT treatment (10-50 uM)
      prevents the increase in hemolysis and Reactive Oxygen Species (ROS) generation
      induced by exposure of cells to micromolar HgCl2 concentrations as well as the
      decrease in GSH intracellular levels. Moreover, as indicated by scanning electron
      microscopy, the morphological alterations are also significantly reduced by HT co
      treatment. Taken together our data provide the first experimental evidence that
      HT has the potential to counteract mercury toxicity. The reported effect may be
      regarded as an additional mechanism underlying the beneficial cardio-protective
      effects of this dietary antioxidant, also endowed with significant anti
      atherogenic and anti-inflammatory properties. 

PMID- 25957743
TI  - Acute toxicological studies of the main organosulfur compound derived from Allium
      sp. intended to be used in active food packaging.
AB  - Some plant extracts have been proposed as potential alternative to the use of
      synthetic preservatives in the food industry. Among those, extracts from Allium
      species exhibit interesting antimicrobial and antioxidant properties for the food
      packaging industry. The present work aims to assess the usefulness and potential
      safety of the major organosulfur compound present in a commercial Allium sp.
      extract (PROALLIUM AP(r)), namely propyl thiosulfinate oxide (PTSO). For this
      purpose, its antimicrobial activity was studied in a wide range of
      microorganisms. Moreover, cytotoxicity and ultrastructural cellular damages
      caused by PTSO were studied in two human cell lines, Caco-2 and HepG2, being the
      colonic cells more sensitive to this compound. Finally, the protective role of
      PTSO against an induced oxidative situation was evaluated in the human intestinal
      Caco-2 cells. The results revealed damage at high concentration, although no
      significant adverse effects were recorded for the concentration to be used in
      food packaging. Moreover, the in vivo study also revealed the potential safety
      use at the established concentrations. In addition, the antimicrobial properties
      and the antioxidant role of PTSO were confirmed. Therefore, this compound could
      be considered as a good natural alternative to synthetic preservatives used in
      the food packaging industry. 

PMID- 25957744
TI  - Semiautomatic computer-aided classification of degenerative lumbar spine disease
      in magnetic resonance imaging.
AB  - BACKGROUND: Computer-aided diagnosis (CAD) methods for detecting and classifying
      lumbar spine disease in Magnetic Resonance imaging (MRI) can assist radiologists
      to perform their decision-making tasks. In this paper, a CAD software has been
      developed able to classify and quantify spine disease (disc degeneration,
      herniation and spinal stenosis) in two-dimensional MRI. METHODS: A set of 52
      lumbar discs from 14 patients was used for training and 243 lumbar discs from 53
      patients for testing in conventional two-dimensional MRI of the lumbar spine. To
      classify disc degeneration according to the gold standard, Pfirrmann
      classification, a method based on the measurement of disc signal intensity and
      structure was developed. A gradient Vector Flow algorithm was used to extract
      disc shape features and for detecting contour abnormalities. Also, a signal
      intensity method was used for segmenting and detecting spinal stenosis. Novel
      algorithms have also been developed to quantify the severity of these
      pathologies. Variability was evaluated by kappa (k) and intra-class correlation
      (ICC) statistics. RESULTS: Segmentation inaccuracy was below 1%. Almost perfect
      agreement, as measured by the k and ICC statistics, was obtained for all the
      analyzed pathologies: disc degeneration (k=0.81 with 95% CI=[0.75..0.88]) with a
      sensitivity of 95.8% and a specificity of 92.6%, disc herniation (k=0.94 with 95%
      CI=[0.87..1]) with a sensitivity of 60% and a specificity of 87.1%, categorical
      stenosis (k=0.94 with 95% CI=[0.90..0.98]) and quantitative stenosis (ICC=0.98
      with 95% CI=[0.97..0.98]) with a sensitivity of 70% and a specificity of 81.7%.
      DISCUSSION: The proposed methods are reproducible and should be considered as a
      possible alternative when compared to reference standards.

PMID- 25957745
TI  - Image-based computational simulation of sub-endothelial LDL accumulation in a
      human right coronary artery.
AB  - Accumulation of low density lipoproteins (LDL) in the vessel wall is suggested as
      the initiator of atherosclerosis and coronary stenosis. This process is
      associated with the performance of endothelium layer that regulates entering of
      macromolecules to the vessel wall. Therefore, the present study aims to
      investigate sub-endothelial accumulation of LDL molecules in a coronary tree and
      predict atherosclerosis prone sites. Non-Newtonian blood flow is simulated for
      normal and hypertensive conditions through the lumen of a right coronary artery
      reconstructed from computed tomography (CT) images. A three-pore model is
      implemented as the endothelium boundary condition and hence, plasma flow and LDL
      transport are simulated within the arterial wall. Based on the pore model,
      endothelium pathways divide into normal junctions, vesicles and leaky junctions.
      Most of LDL molecules pass through the leaky junctions that arise at locations
      with low wall shear stress (WSS). Results indicate that increase in the number of
      leaky junctions at branch points with low WSS can lead to both elevated levels of
      sub-endothelial LDL accumulation and atherosclerosis risk. Findings reveal that
      at the branch points with disturbed flow, sub-endothelial concentration of LDL
      for the hypertensive condition is higher than the normal condition, however for
      the rest of regions with uniform geometry and unidirectional flow, this is
      reversed. Comparisons of non-Newtonian and Newtonian flows show mean increases of
      34% and 13% in the sub-endothelial concentrations of Newtonian flows during the
      normal and hypertensive conditions, respectively. 

PMID- 25957746
TI  - Thoracic cavity definition for 3D PET/CT analysis and visualization.
AB  - X-ray computed tomography (CT) and positron emission tomography (PET) serve as
      the standard imaging modalities for lung-cancer management. CT gives anatomical
      details on diagnostic regions of interest (ROIs), while PET gives highly specific
      functional information. During the lung-cancer management process, a patient
      receives a co-registered whole-body PET/CT scan pair and a dedicated high
      resolution chest CT scan. With these data, multimodal PET/CT ROI information can
      be gleaned to facilitate disease management. Effective image segmentation of the
      thoracic cavity, however, is needed to focus attention on the central chest. We
      present an automatic method for thoracic cavity segmentation from 3D CT scans. We
      then demonstrate how the method facilitates 3D ROI localization and visualization
      in patient multimodal imaging studies. Our segmentation method draws upon digital
      topological and morphological operations, active-contour analysis, and key organ
      landmarks. Using a large patient database, the method showed high agreement to
      ground-truth regions, with a mean coverage=99.2% and leakage=0.52%. Furthermore,
      it enabled extremely fast computation. For PET/CT lesion analysis, the
      segmentation method reduced ROI search space by 97.7% for a whole-body scan, or
      nearly 3 times greater than that achieved by a lung mask. Despite this reduction,
      we achieved 100% true-positive ROI detection, while also reducing the false
      positive (FP) detection rate by >5 times over that achieved with a lung mask.
      Finally, the method greatly improved PET/CT visualization by eliminating false
      PET-avid obscurations arising from the heart, bones, and liver. In particular,
      PET MIP views and fused PET/CT renderings depicted unprecedented clarity of the
      lesions and neighboring anatomical structures truly relevant to lung-cancer
      assessment. 

PMID- 25957747
TI  - Permeability test for transdermal and local therapeutic patches using Skin PAMPA
      method.
AB  - Using the skin as absorption site presents unique advantages that have
      facilitated the progression of transdermal drug delivery in the past decades.
      Efforts in drug research have been devoted to find a quick and reproducible model
      for predicting the skin permeation of molecules. The Parallel Artificial Membrane
      Permeability Assay (PAMPA) has been extended for prediction of transdermal
      permeation by developing a model with completely artificial membrane, which can
      mimic the permeation through the stratum corneum. The present study aims to
      extend the Skin PAMPA method for testing transdermal and local therapeutic
      patches. The original method was modified and seven commercially available
      transdermal and local therapeutic patches with four different active
      pharmaceutical ingredients (nicotine, fentanyl, rivastigmine and ketoprofen) were
      studied. Data were compared to the declared delivery rates that are indicated by
      the manufacturers. Ex vivo permeation study was also performed in order to
      compare the permeated amount of the released drugs obtained by the two methods.
      The flux across the artificial membrane as well as the human skin (ex vivo) has
      been calculated and compared to the in vivo flux deduced from the labelled
      delivery rate and the active area of the patches. The results suggest that Skin
      PAMPA system can serve as a useful tool for evaluation and classification of the
      transdermal patches. 

PMID- 25957748
TI  - Comparing treatment effects of oral THC on simulated and on-the-road driving
      performance: testing the validity of driving simulator drug research.
AB  - RATIONALE: The driving simulator provides a safe and controlled environment for
      testing driving behaviour efficiently. The question is whether it is sensitive to
      detect drug-induced effects. OBJECTIVE: The primary aim of the current study was
      to investigate the sensitivity of the driving simulator for detecting drug
      effects. As a case in point, we investigated the dose-related effects of oral
      ?(9)-tetrahydrocannabinol (THC), i.e. dronabinol, on simulator and on-the-road
      driving performance in equally demanding driving tasks. METHOD: Twenty-four
      experienced driver participants were treated with dronabinol (Marinol(r); 10 and
      20 mg) and placebo. Dose-related effects of the drug on the ability to keep a
      vehicle in lane (weaving) and to follow the speed changes of a lead car (car
      following) were compared within subjects for on-the-road versus in-simulator
      driving. Additionally, the outcomes of equivalence testing to alcohol-induced
      effects were investigated. RESULTS: Treatment effects found on weaving when
      driving in the simulator were comparable to treatment effects found when driving
      on the road. The effect after 10 mg dronabinol was however less strong in the
      simulator than on the road and inter-individual variance seemed higher in the
      simulator. There was, however, a differential treatment effect of dronabinol on
      reactions to speed changes of a lead car (car following) when driving on the road
      versus when driving in the simulator. CONCLUSION: The driving simulator was
      proven to be sensitive for demonstrating dronabinol-induced effects particularly
      at higher doses. Treatment effects of dronabinol on weaving were comparable with
      driving on the road but inter-individual variability seemed higher in the
      simulator than on the road which may have potential effects on the clinical
      inferences made from simulator driving. Car following on the road and in the
      simulator were, however, not comparable.

PMID- 25957749
TI  - Upregulation of Slc38a1 Gene Along with Promotion of Neurosphere Growth and
      Subsequent Neuronal Specification in Undifferentiated Neural Progenitor Cells
      Exposed to Theanine.
AB  - We have shown marked promotion of both cluster growth and neuronal specification
      in pluripotent P19 cells with overexpression of solute carrier 38a1 (Slc38a1),
      which is responsible for membrane transport of glutamine. In this study, we
      evaluated pharmacological profiles of the green tea amino acid ingredient
      theanine, which is a good substrate for glutamine transporters, on proliferation
      and neuronal specification in neural progenitor cells from embryonic rat
      neocortex. Sustained exposure to theanine, but not glutamine, accelerated the
      growth of neurospheres composed of proliferating cells and 3-(4,5-dimethyl-2
      thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) reducing activity at
      concentrations of 1-100 MUM in undifferentiated progenitor cells. Such prior
      exposure to theanine promoted spontaneous and induced commitment to a neuronal
      lineage with concomitant deteriorated astroglial specification. Selective
      upregulation was seen in the expression of Slc38a1 in progenitor cells cultured
      with theanine. Similarly significant increases in cluster growth and MTT reducing
      activity were found in P19 cells cultured with theanine for 4 days. Luciferase
      activity was doubled in a manner sensitive to the deletion of promoter regions in
      P19 cells with a luciferase reporter plasmid of the Slc38a1 promoter after
      sustained exposure to theanine for 4 days. Overexpression of X-box binding
      protein-1 led to a marked increase in luciferase activity in P19 cells
      transfected with the Slc38a1 reporter plasmid. These results suggest that
      theanine accelerates cellular proliferation and subsequent neuronal specification
      through a mechanism relevant to upregulation of Slc38a1 gene in undifferentiated
      neural progenitor cells.

PMID- 25957750
TI  - Spatial Learning Requires mGlu5 Signalling in the Dorsal Hippocampus.
AB  - We examined the role of hippocampal metabotropic glutamate receptor 5 (mGlu5) in
      spatial learning and memory. Although it has been shown that mGlu5 signalling is
      required for certain forms of learning and memory, its role in spatial learning
      is unclear since studies using pharmacological or knockout mice models provide
      inconsistent findings. Additionally, the location in the brain where mGlu5
      signalling may modulate such learning is yet to be precisely delineated. We
      stereotaxically injected rAAV-Cre into the dorsal hippocampus of mGlu5(loxP/loxP)
      mice to knockdown mGlu5 in that region. We show for the first time that knockdown
      of mGlu5 in the dorsal hippocampus is sufficient to impair spatial learning in
      Morris Water Maze. Locomotor activity and memory retrieval were unaffected by the
      mGlu5 knockdown. Taken together, these findings support a key role for dorsal
      hippocampal mGlu5 signalling in spatial learning.

PMID- 25957751
TI  - Child advocacy center multidisciplinary team decision and its association to
      child protective services outcomes.
AB  - Limited studies exist evaluating the multidisciplinary team (MDT) decision-making
      process and its outcomes. This study evaluates the MDT determination of the
      likelihood of child sexual abuse (CSA) and its association to the outcome of the
      child protective services (CPS) disposition. A retrospective cohort study of CSA
      patients was conducted. The MDT utilized an a priori Likert rating scale to
      determine the likelihood of abuse. Subjects were dichotomized into high versus
      low/intermediate likelihood of CSA as determined by the MDT. Clinical and
      demographic characteristics were compared based upon MDT and CPS decisions.
      Fourteen hundred twenty-two patients were identified. A high likelihood for abuse
      was determined in 997 cases (70%). CPS substantiated or indicated the allegation
      of CSA in 789 cases (79%, Kappa 0.54). Any CSA disclosure, particularly moderate
      risk disclosure (AOR 59.3, 95% CI 26.50-132.80) or increasing total number of CSA
      disclosures (AOR 1.3, 95% CI 1.11-1.57), was independently associated with a high
      likelihood for abuse determination. Specific clinical features associated with
      discordant cases in which MDT determined high likelihood for abuse and CPS did
      not substantiate or indicate CSA included being white or providing a low risk CSA
      disclosure or other non-CSA disclosure. MDT determination regarding likelihood of
      abuse demonstrated moderate agreement to CPS disposition outcome. CSA disclosure
      is predictive of the MDT determination for high likelihood of CSA. Agreement
      between MDT determination and CPS protection decisions appear to be driven by the
      type of disclosures, highlighting the importance of the forensic interview in
      ensuring appropriate child protection plans. 

PMID- 25957752
TI  - Physical maltreatment of children with autism in Henan province in China: A cross
      sectional study.
AB  - The aim of this study was to investigate the frequency of child physical
      maltreatment (CPM) in children with autism aged 2-5 years in Henan province
      (China), and to explore the risk factors for severe CPM in these children. This
      cross-sectional study was performed at the Psychology Clinic of the Third
      Affiliated Hospital of Zhengzhou University between September 2012 and September
      2013 with 180 parents of children with autism. Children and parents had no
      history of any cognitive therapy. The childhood autism rating scale (CARS) was
      used to evaluate the severity of autism in children. Data on parental CPM during
      the past 3 months were collected from parental self-reporting. Logistic
      regression was used to investigate the risk factors of severe CPM. CPM was self
      reported by 88% of the parents of children with autism. One hundred and fifty
      four of these cases were in the minor CPM group (86%) and 64 in the severe CPM
      group (36%). Most cases of severe CPM were unlikely to have caused injury.
      Univariate analyses showed that child's age (p=.018), age started to speak
      (p=.043) and CARS score (p=.048) were associated with severe CPM. Child's age
      (p=.011) and CARS score (p=.041) were independently associated with severe CPM.
      The risk of severe CPM increased with age and CARS score. Our findings showed
      that CPM is widespread in families of children with autism in Central China and
      more knowledge should be provided to parents of children with autism,
      particularly in cases of severe autism (those with high CARS scores). 

PMID- 25957753
TI  - Reducing soil erosion and nutrient loss on sloping land under crop-mulberry
      management system.
AB  - Sloping croplands could result in soil erosion, which leads to non-point source
      pollution of the aquatic system in the Three Gorges Reservoir Region. Mulberry, a
      commonly grown cash plant in the region, is traditionally planted in contour
      hedgerows as an effective management practice to control soil erosion and non
      point source pollution. In this field study, surface runoff and soil N and P loss
      on sloping land under crop-mulberry management were investigated. The experiments
      consisted of six crop-mulberry treatments: Control (no mulberry hedgerow with
      mustard-corn rotation); T1 (two-row contour mulberry with mustard-corn rotation);
      T2 (three-row contour mulberry with mustard-corn rotation); T3 (border mulberry
      and one-row contour mulberry with mustard-corn rotation); T4 (border mulberry
      with mustard-corn rotation); T5 (two-row longitudinal mulberry with mustard). The
      results indicated that crop-mulberry systems could effectively reduce surface
      runoff and soil and nutrient loss from arable slope land. Surface runoff from T1
      (342.13 m(3) hm(-2)), T2 (260.6 m(3) hm(-2)), T3 (113.13 m(3) hm(-2)), T4 (114
      m(3) hm(-2)), and T5 (129 m(3) hm(-2)) was reduced by 15.4, 35.6, 72.0, 71.8, and
      68.1%, respectively, while soil loss from T1 (0.21 t hm(-2)), T2 (0.13 t hm(-2)),
      T3 (0.08 t hm(-2)), T4 (0.11 t hm(-2)), and T5 (0.12 t hm(-2)) was reduced by
      52.3, 70.5, 81.8, 75.0, and 72.7%, respectively, as compared with the control.
      Crop-mulberry ecosystem would also elevate soil N by 22.3% and soil P by 57.4%,
      and soil nutrient status was contour-line dependent.

PMID- 25957754
TI  - Assessment of Spectral Doppler for an Array-Based Preclinical Ultrasound Scanner
      Using a Rotating Phantom.
AB  - Velocity measurement errors were investigated for an array-based preclinical
      ultrasound scanner (Vevo 2100, FUJIFILM VisualSonics, Toronto, ON, Canada). Using
      a small-size rotating phantom made from a tissue-mimicking material, errors in
      pulse-wave Doppler maximum velocity measurements were observed. The extent of
      these errors was dependent on the Doppler angle, gate length, gate depth, gate
      horizontal placement and phantom velocity. Errors were observed to be up to 172%
      at high beam-target angles. It was found that small gate lengths resulted in
      larger velocity errors than large gate lengths, a phenomenon that has not
      previously been reported (e.g., for a beam-target angle of 0 degrees , the error
      was 27.8% with a 0.2-mm gate length and 5.4% with a 0.98-mm gate length). The
      error in the velocity measurement with sample volume depth changed depending on
      the operating frequency of the probe. Some edge effects were observed in the
      horizontal placement of the sample volume, indicating a change in the array
      aperture size. The error in the velocity measurements increased with increased
      phantom velocity, from 22% at 2.4 cm/s to 30% at 26.6 cm/s. To minimise the
      impact of these errors, an angle-dependent correction factor was derived based on
      a simple ray model of geometric spectral broadening. Use of this angle-dependent
      correction factor reduces the maximum velocity measurement errors to <25% in all
      instances, significantly improving the current estimation of maximum velocity
      from pulse-wave Doppler ultrasound. 

PMID- 25957755
TI  - Simulation of Low-Intensity Ultrasound Propagating in a Beagle Dog Dentoalveolar
      Structure to Investigate the Relations between Ultrasonic Parameters and Cementum
      Regeneration.
AB  - The therapeutic effect of low-intensity pulsed ultrasound on orthodontically
      induced inflammatory root resorption is believed to be brought about through
      mechanical signals induced by the low-intensity pulsed ultrasound. However, the
      stimulatory mechanism triggering dental cell response has not been clearly
      identified yet. The aim of this study was to evaluate possible relations between
      the amounts of new cementum regeneration and ultrasonic parameters such as
      pressure amplitude and time-averaged energy density. We used the finite-element
      method to simulate the previously published experiment on ultrasonic wave
      propagation in the dentoalveolar structure of beagle dogs. Qualitative relations
      between the thickness of the regenerated cementum in the experiment and the
      ultrasonic parameters were observed. Our results indicated that the areas of the
      root surface with greater ultrasonic pressure were associated with larger amounts
      of cementum regeneration. However, the establishment of reliable quantitative
      correlations between ultrasound parameters and cementum regeneration requires
      more experimental data and simulations. 

PMID- 25957756
TI  - Arterial supply to the soleus muscle: an anatomical study with emphasis on its
      application in the pedicle flap surgery.
AB  - PURPOSE: To study the various patterns in the extra muscular part of arterial
      supply to the soleus muscle. METHODS: The study was carried out using 38 adult
      cadaveric lower limbs which were available from the Department of Anatomy of our
      institution. The vascular branches to the soleus were identified and traced till
      their point of entry into the soleus. These were considered as extramuscular
      branches (EMB) to the soleus. The distances of first and last branches from each
      artery were measured from the apex of head of fibula to their point of entry into
      the soleus and were expressed as proportion to the length of soleus. RESULTS: The
      present study observed that the soleus muscle is supplied by EMB of popliteal,
      posterior tibial and peroneal arteries. In 42.1% cases, there was no direct EMB
      from the popliteal artery to the soleus. The EMB of popliteal artery were located
      between 3.2 and 24.6% of the length of soleus. The EMB from the posterior tibial
      and peroneal arteries were located between 6.8-97.1% and 5.7-94.9% of the length
      of soleus, respectively. The proximal 25% of length of soleus received EMB from
      all the three arteries. CONCLUSIONS: The present study has provided additional
      information on the various patterns in the extra muscular part of arterial supply
      to the soleus muscle. This knowledge is important to the plastic and orthopedic
      surgeons while performing the pedicle flap surgeries. Our opinion is that the
      proximally based soleal muscle flaps are more beneficial in the surgical
      practice.

PMID- 25957757
TI  - Increased resolution of aromatic cross peaks using alternate 13C labeling and
      TROSY.
AB  - For typical globular proteins, contacts involving aromatic side chains would
      constitute the largest number of distance constraints that could be used to
      define the structure of proteins and protein complexes based on NOE contacts.
      However, the (1)H NMR signals of aromatic side chains are often heavily
      overlapped, which hampers extensive use of aromatic NOE cross peaks. Some of this
      overlap can be overcome by recording (13)C-dispersed NOESY spectra. However, the
      resolution in the carbon dimension is rather low due to the narrow dispersion of
      the carbon signals, large one-bond carbon-carbon (C-C) couplings, and line
      broadening due to chemical shift anisotropy (CSA). Although it has been noted
      that the CSA of aromatic carbons could be used in TROSY experiments for enhancing
      resolution, this has not been used much in practice because of complications
      arising from large aromatic one-bond C-C couplings, and 3D or 4D carbon dispersed
      NOESY are typically recorded at low resolution hampering straightforward peak
      assignments. Here we show that the aromatic TROSY effect can optimally be used
      when employing alternate (13)C labeling using 2-(13)C glycerol, 2-(13)C pyruvate,
      or 3-(13)C pyruvate as the carbon source. With the elimination of the strong one
      bond C-C coupling, the TROSY effect can easily be exploited. We show that (1)H
      (13)C TROSY spectra of alternately (13)C labeled samples can be recorded at high
      resolution, and we employ 3D NOESY aromatic-TROSY spectra to obtain valuable
      intramolecular and intermolecular cross peaks on a protein complex.

PMID- 25957758
TI  - Heart valve calcification in patients with type 2 diabetes and nonalcoholic fatty
      liver disease.
AB  - PURPOSE: Aortic valve sclerosis (AVS) and mitral annulus calcification (MAC) are
      two powerful predictors of adverse cardiovascular outcomes in patients with type
      2 diabetes, but the etiology of valvular calcification is uncertain. Nonalcoholic
      fatty liver disease (NAFLD) is an emerging cardiovascular risk factor and is very
      common in type 2 diabetes, but whether NAFLD is associated with valvular
      calcification in this group of patients is presently unknown. METHODS: We
      undertook a cross-sectional study of 247 consecutive type 2 diabetic outpatients
      with no previous history of heart failure, valvular heart diseases (aortic
      stenosis, mitral stenosis, moderate or severe aortic and mitral regurgitation) or
      hepatic diseases. Presence of MAC and AVS was detected by echocardiography. NAFLD
      was diagnosed by ultrasonography. RESULTS: Overall, 139 (56.3%) patients had no
      heart valve calcification (HVC-0), 65 (26.3%) patients had one valve affected
      (HVC-1) and 43 (17.4%) patients had both valves affected (HVC-2). 175 (70.8%)
      patients had NAFLD and the prevalence of this disease markedly increased in
      patients with HVC-2 compared with either HVC-1 or HVC-0 (86.1% vs. 83.1% vs.
      60.4%, respectively; p < 0.001). NAFLD was significantly associated with AVS
      and/or MAC (unadjusted-odds ratio 3.51, 95% CI 1.89-6.51, p < 0.001). Adjustments
      for age, sex, waist circumference, smoking, blood pressure, hemoglobin A1c, LDL
      cholesterol, kidney function parameters, medication use and echocardiographic
      variables did not appreciably weaken this association (adjusted-odds ratio 2.70,
      95% CI 1.23-7.38, p < 0.01). CONCLUSIONS: Our results show that NAFLD is an
      independent predictor of cardiac calcification in both the aortic and mitral
      valves in patients with type 2 diabetes.

PMID- 25957759
TI  - Transient global amnesia and Takotsubo syndrome: would cerebral blood flow brain
      scan be of any help?

PMID- 25957760
TI  - Maternal and neonatal outcomes of Hepatitis C positive women attending a
      midwifery led drug and alcohol service: A West Australian perspective.
AB  - BACKGROUND: the Women and Newborn Drug and Alcohol Service (WANDAS) is a
      specialist, midwifery-led service providing pregnancy care to women dealing with
      alcohol and other drug (AOD) use, at the sole tertiary maternity hospital in
      Western Australia. AIM: to assess the antenatal, intrapartum and neonatal
      outcomes of women with Hepatitis C (HCV) who attended the WANDAS service between
      2009 and 2012. DESIGN: this retrospective cohort study used data obtained from
      computerised midwifery records. Univariate comparisons between those who were HCV
      positive and those who were not, were performed. Multivariable logistic
      regression was utilised to investigate the simultaneous factors associated with
      being HCV positive and an opiate user. FINDINGS: the incidence of HCV in this
      cohort was 37% (213 of 570). Compared to those who were HCV negative those who
      were positive were more likely to: be older (P<0.001); use opioids in pregnancy
      (P<0.001); be an intravenous drug user (P<0.001); engage in polysubstance use
      (P<0.001); and receive an induction of labour (P=0.036). There were no
      intrapartum characteristics found to be significant at a multivariate level
      associated with being HCV positive and an opiate user, but there were a couple of
      neonatal complications. These were having a baby admitted to Special Care Nursery
      (OR 1.95, 95% CI 1.33-2.88, P<0.001) and a baby at increased risk of being
      diagnosed with neonatal abstinence syndrome (OR 3.40, 95% CI 2.24-5.15, P<0.001).
      CONCLUSION: our findings highlight the complexity of caring for pregnant women
      who are HCV positive, they also highlight that all pregnant women who are AOD
      users are an at risk population. IMPLICATIONS FOR PRACTICE: these results improve
      our understanding of the obstetric and midwifery issues associated with caring
      for pregnant women who are HCV positive and the value of provision of specialist
      care from a multidisciplinary team, led by a consultant midwife.

PMID- 25957761
TI  - Sudden onset of Chiari malformation type 1 in a young child after trauma.
AB  - INTRODUCTION: Chiari 1 malformation is a rare craniovertebral junction
      malformation accounting up to 1 case in every 1000 newborns per year. It is
      characterized by herniation of cerebellar tonsils below the foramen magnum
      sometimes with syringomyelia. Usually, patients have a long history of slowly
      progressive neurological symptoms. Uncommonly, Chiari 1 malformation could
      present with a sudden onset, also after trauma. Few cases are reported about
      young children. METHODS: The authors report a case of a 6-month child with
      symptoms at onset after a mild trauma. The pertinent literature is reviewed.
      CONCLUSIONS: Symptoms of Chiari 1 malformation are usually slowly progressive.
      Few cases have been reported of the sudden onset of symptoms, some of these after
      trauma. In young children, the clinical setting could be insidious and
      potentially lethal. A sudden onset of Chiari 1 malformation must be considered as
      a consequence of trauma, usually after performing a brain MRI. Management of
      these cases is still controversial, and surgery may be indicated in managing
      symptoms; however, it seems to not affect clinical outcome.

PMID- 25957762
TI  - Low-grade ependymoma with late metastasis: autopsy case study and literature
      review.
AB  - INTRODUCTION: Ependymoma metastasis occurs usually along with local recurrence
      within 7 years after the initial diagnosis. Later spinal metastasis without local
      recurrence after the surgical resection has been rarely reported in patients with
      low-grade ependymomas but not with high-grade ependymomas. Here, we present a
      case with autopsy revealing late extensive supratentorial metastasis of a fourth
      ventricle classic WHO grade II ependymoma with no local recurrence or spinal
      metastasis. METHODS: A 4-year-old boy underwent a gross total resection (GTR) of
      the fourth ventricle ependymoma and postoperative radiation therapy. Follow-up
      MRI showed no recurrence for the next 7 years, but a half year later, extra-axial
      tumors in the left cerebellopontine angle and right frontal lobe were observed.
      GTR of the left cerebellopontine angle ependymoma was performed, followed by
      additional radiation therapy. RESULTS: He was stable for the following 2 years
      before MRI revealed growth of the right frontal tumor and new lesions. GTR of the
      right frontal tumor demonstrated similar pathologic features of ependymoma.
      Despite chemotherapy, follow-up MRIs exhibited increasing numbers and sizes of
      supratentorial tumors but no infratentorial or spinal tumors. He died 15 years
      after the initial diagnosis. Postmortem brain examination confirmed the
      supratentorial subarachnoid dissemination with multifocal metastases of classic
      ependymomas but no recurrence at the infratentorial sites. CONCLUSION: Our case
      study and literature review suggest that low-grade ependymomas under the current
      WHO classification have the risk of late metastasis. Therefore, long-term follow
      up of the whole neuroaxis is more important for the patients with low-grade
      ependymomas even in the absence of local recurrence.

PMID- 25957763
TI  - An extraocular non-invasive transscleral LED-endoilluminator for eye speculum
      integration.
AB  - PURPOSE: Conventional chandelier-endoilluminators used for pars-plana vitrectomy
      consist of a light-emitting tip attached to an optical fibre. The tip requires
      introduction into the ocular space through an incision. To achieve complete
      illumination of the intraocular space, the introduction of more than just one tip
      is sometimes necessary. An extraocular vitreoretinal LED-endoilluminator
      discussed in this paper represents a new approach to illuminate the intraocular
      space. The light source is integrated into a speculum and firmly apposed to the
      sclera. This approach offers the advantage of effectively illuminating the
      interior of the eye even though the procedure is non-invasive. Furthermore, this
      approach significantly reduces the risk of damage to the retina by phototoxic
      effects. METHODS: A round white LED was used as a light source. By integrating
      the light source into a speculum, the LED was firmly held against the sclera.
      Thus, the ocular space was illuminated transsclerally. As a result, indirect
      uniform illumination of the complete intraocular space was achieved. The
      prototype was developed considering the relevant international standards. Porcine
      eyes were used because their properties are similar to those of human eyes.
      RESULTS: Porcine eyes could be acceptably illuminated with the selected LED. The
      LED-endoilluminator conforms with international standards for endoillumination.
      Thus, possible photochemical and thermal risks are considered and reduced to a
      minimum. CONCLUSIONS: A novel LED-endoilluminator which can be attached to a
      speculum was developed. The system does not need any connection to an external
      light source and, consequently, also avoids usage of an optical fibre. Regular
      and uniform illumination of the intraocular space was achieved by transmitted and
      scattered visible irradiation, avoiding an incision. The duration of potential
      light exposure, compared to existing illumination systems, can be significantly
      increased. This is also true when the illuminator is not directly placed over the
      pars-plana and the distance to the retina is reduced. Only a part of the light
      reaches the retina and the fraction of short wavelength becomes very small.
      Increased safety of the system results from now being able to increase the
      exposure time and reduce phototoxic stress to the retina.

PMID- 25957764
TI  - Serum and aqueous xanthine oxidase levels, and mRNA expression in anterior lens
      epithelial cells in pseudoexfoliation.
AB  - PURPOSE: The aim of this study was to determine serum and aqueous xanthine
      oxidase (XO) levels, and mRNA expression in anterior lens epithelial cells in
      pseudoexfoliation (PEX). METHODS: In this prospective study, serum, aqueous and
      anterior lens capsules were taken from 21 patients with PEX and 23 normal
      subjects who had undergone routine cataract surgery. Serum and aqueous XO levels
      were analyzed using the colorimetric method. mRNA expression of XO in anterior
      lens epithelial cells was evaluated using reverse transcription polymerase chain
      reaction analysis. RESULTS: Serum XO levels (means +/- standard deviations) were
      207.0 +/- 86.1 IU/mL and 240.6 +/- 114.1 IU/mL in the normal and PEX groups,
      respectively (p = 0.310). Aqueous XO levels (means +/- standard deviations) were
      65.5 +/- 54.3 IU/mL in the normal group and 130.5 +/- 117.4 IU/mL in the PEX
      group (p = 0.028). There was a 2.9 fold decrease in mRNA expression in anterior
      lens epithelial cells of PEX, which is significantly lower than the normal group
      (p = 0.01). CONCLUSIONS: Higher aqueous XO levels lacking associated different
      serum XO suggests higher oxidative stress in the aqueous. Higher aqueous XO
      levels in PEX with decreased mRNA expression in anterior lens epithelial cells
      indicate possible overexpression of XO in other structures related to the
      aqueous.

PMID- 25957765
TI  - Mean platelet volume in retinopathy of prematurity.

PMID- 25957767
TI  - Biselyngbyasides, cytotoxic marine macrolides, are novel and potent inhibitors of
      the Ca(2+) pumps with a unique mode of binding.
AB  - Biselyngbyasides (BLSs), macrolides from a marine cyanobacterium, are cytotoxic
      natural products whose target molecule is unknown. Here we report that BLSs are
      high affinity (Ki~10 nM) inhibitors of Ca(2+)-pumps with a unique binding mode.
      The crystal structures of the Ca(2+)-pump in complex with BLSs at 3.2-3.5 A
      resolution show that BLSs bind to the pump near the cytoplasmic surface of the
      transmembrane region. The crystal structures and activity measurement of BLS
      analogs allow us to identify the structural features that confer high potency to
      BLSs as inhibitors of the pump.

PMID- 25957766
TI  - Induction of heat shock protein HSPA6 (HSP70B') upon HSP90 inhibition in cancer
      cell lines.
AB  - Genome-wide transcript profiling to elucidate responses to HSP90 inhibition
      revealed strong induction of HSPA6 in MCF-7 cells treated with 17-AAG. Time- and
      dose dependent induction of HSPA6 (confirmed by qPCR and Western Blots) occurred
      also upon treatment with Radicicol, another HSP90 inhibitor. HSPA6 was not
      detectable in untreated cells or cells treated with toxins that do not inhibit
      HSP90, or upon applying oxidative stress. Thus, HSPA6 induction is not a general
      response to cytotoxic insults. Modulation of HSPA6 levels by siRNA-mediated
      inhibition or recombinant expression did not influence 17-AAG mediated cell
      death. HSPA6 induction as a consequence of HSP90 inhibition occurs in various
      (but not all) cell lines and may be a more specific marker for HSP90 inhibition
      than induction of other HSP70 proteins. 

PMID- 25957768
TI  - Candida albicans erythroascorbate peroxidase regulates intracellular
      methylglyoxal and reactive oxygen species independently of D-erythroascorbic
      acid.
AB  - Candida albicans D-erythroascorbate peroxidase (EAPX1), which can catalyze the
      oxidation of D-erythroascorbic acid (EASC) to water, was observed to be inducible
      in EAPX1-deficient and EAPX1-overexpressing cells via activity staining. EAPX1
      deficient cells have remarkably increased intracellular reactive oxygen species
      and methylglyoxal independent of the intracellular EASC content. The increased
      methylglyoxal caused EAPX1-deficient cells to activate catalase-peroxidase and
      cytochrome c peroxidase, which led to defects in cell growth, viability,
      mitochondrial respiration, filamentation and virulence. These findings indicate
      that EAPX1 mediates cell differentiation and virulence by regulating
      intracellular methylglyoxal along with oxidative stresses, regardless of
      endogenous EASC biosynthesis or alternative oxidase expression.

PMID- 25957770
TI  - Chemical chronobiology: Toward drugs manipulating time.
AB  - Circadian clocks are endogenous timing systems orchestrating the daily regulation
      of a huge variety of physiological, metabolic and behavioral processes. These
      clocks are important for health - in mammals, their disruption leads to a diverse
      number of pathologies. While genetic and biochemical approaches largely uncovered
      the molecular bases of circadian rhythm generation, chemical biology strategies
      targeting the circadian oscillator by small chemical compounds are increasingly
      developed. Here, we review the recent progress in the identification of small
      molecules modulating circadian rhythms. We focus on high-throughput screening
      approaches using circadian bioluminescence reporter cell lines as well as
      describe alternative mechanistic screens. Furthermore, we discuss the potential
      for chemical optimization of small molecule ligands with regard to the recent
      progress in structural chronobiology. 

PMID- 25957769
TI  - Clec4g (LSECtin) interacts with BACE1 and suppresses Abeta generation.
AB  - beta-Site amyloid precursor protein cleaving enzyme-1 (BACE1) is a central
      molecule in Alzheimer's disease (AD). It cleaves amyloid precursor protein (APP)
      to produce the toxic amyloid-beta (Abeta) peptides. Thus, a novel BACE1 modulator
      could offer a new therapeutic strategy for AD. We report that C-type lectin-like
      domain family 4, member g (Clec4g, also designated as LSECtin) interacts with
      BACE1 in mouse brain and cultured cells. Overexpression of Clec4g suppressed
      BACE1-mediated Abeta generation, and affected the intracellular distribution of
      BACE1 but not its catalytic activity. These results highlight a novel role of
      Clec4g in negatively regulating BACE1 function. 

PMID- 25957771
TI  - Transforming growth factor beta and bone morphogenetic protein actions in brain
      tumors.
AB  - Members of the transforming growth factor beta (TGF-beta) family are implicated
      in the biology of several cancers. Here we focus on malignancies of the brain and
      examine the TGFbeta and the bone morphogenetic protein (BMP) signaling branches
      of the family. These pathways exhibit context-dependent actions during
      tumorigenesis, acting either as tumor suppressors or as pro-tumorigenic agents.
      In the brain, the TGF-betas associate with oncogenic development and progression
      to the more malignant state. Inversely, the BMPs suppress tumorigenic potential
      by acting as agents that induce tumor cell differentiation. The latter has been
      best demonstrated in grade IV astrocytomas, otherwise known as glioblastoma
      multiforme. We discuss how the actions of TGF-betas and BMPs on cancer stem cells
      may explain their effects on tumor progression, and try to highlight intricate
      mechanisms that may link tumor cell differentiation to invasion. The focus on TGF
      beta and BMP and their actions in brain malignancies provides a rich territory
      for mechanistic understanding of tumor heterogeneity and suggests ways for
      improved therapeutic intervention, currently being addressed by clinical trials. 

PMID- 25957772
TI  - Reducing systems protecting the bacterial cell envelope from oxidative damage.
AB  - Exposure of cells to elevated levels of reactive oxygen species (ROS) damages
      DNA, membrane lipids and proteins, which can potentially lead to cell death. In
      proteins, the sulfur-containing residues cysteine and methionine are particularly
      sensitive to oxidation, forming sulfenic acids and methionine sulfoxides,
      respectively. The presence of protection mechanisms to scavenge ROS and repair
      damaged cellular components is therefore essential for cell survival. The
      bacterial cell envelope, which constitutes the first protection barrier from the
      extracellular environment, is particularly exposed to the oxidizing molecules
      generated by the host cells to kill invading microorganisms. Therefore, the
      presence of oxidative stress defense mechanisms in that compartment is crucial
      for cell survival. Here, we review recent findings that led to the identification
      of several reducing pathways protecting the cell envelope from oxidative damage.
      We focus in particular on the mechanisms that repair envelope proteins with
      oxidized cysteine and methionine residues and we discuss the major questions that
      remain to be solved. 

PMID- 25957773
TI  - Architectural hallmarks of the pluripotent genome.
AB  - Pluripotent stem cells (PSCs) have the ability to self-renew and are capable of
      generating all embryonic germ layers (Evans and Kaufman, 1981; Thomson et al.,
      1998). PSCs can be isolated from early embryos or may be induced via
      overexpression of pluripotency transcription factors in differentiated cells
      (Takahashi and Yamanaka, 2006). As PSCs hold great promise for regenerative
      medicine, the mechanisms underlying pluripotency and induction thereof are
      studied intensively. Pluripotency is characterized by a unique transcriptional
      program that is in part controlled by an exceptionally plastic regulatory
      chromatin landscape. In recent years, 3D genome configuration has emerged as an
      important regulator of transcriptional control and cellular identity (Taddei et
      al., 2004 [4]; Lanctot et al., 2007 [5]; Gibcus and Dekker, 2013; Misteli, 2009
      [7]). Here we provide an overview of recent findings on the 3D genome
      organization in PSCs and discuss its putative functional role in regulation of
      the pluripotent state. 

PMID- 25957774
TI  - A toolbox for miRNA analysis.
AB  - MicroRNAs (miRNAs) are small regulatory RNAs, which mediate selective repression
      of gene expression. miRNAs play important roles in many natural and pathological
      processes. Numerous tools were developed for their detection and functional
      analysis. There are many excellent articles covering different areas of miRNA
      biology in detail. At the same time, I think there are many colleagues who face a
      miRNA-related research problem and would appreciate having an introductory
      general overview of tools for miRNA analysis, which would help them in
      considering available options. Accordingly, this review provides an elementary
      roadmap to navigate among available tools for miRNA analysis. The most common
      problems and errors observed in miRNA research are also discussed. 

PMID- 25957775
TI  - Cloning and characterization of the Escherichia coli Heptosyltransferase III:
      Exploring substrate specificity in lipopolysaccharide core biosynthesis.
AB  - Bacterial lipopolysaccharide (LPS) molecules are an important cell surface
      component that enables adhesion to surfaces and cell motility, amongst other
      functions. In Escherichia coli, there are multiple Heptosyltransferase enzymes
      involved in the biosynthesis of the core region of LPS. Here we describe the
      first ever cloning, expression, purification and characterization of
      Heptosyltransferase III (HepIII) from E. coli, which catalyzes the addition of an
      L-glycero-D-manno-heptose (Hep) residue to the growing LPS core via an alpha(1
      >7) bond. Inspired by results from our lab on the E. coli HepI, we assessed the
      catalytic efficiency with phospho-Hep2-Kdo2-Lipid A (PH2K2LA) and two deacylated
      analogues.

PMID- 25957776
TI  - 50 years forward: beta cells.
AB  - Our understanding of beta cell development and function has increased
      substantially these past 50 years but much remains to be learned before this
      knowledge can be put to clinical use. A comprehensive business plan will be
      necessary to develop a detailed molecular and functional blueprint of the beta
      cell in health and disease based on an integrated approach involving all
      necessary research disciplines. This blueprint will provide a platform for the
      development of novel therapeutic strategies for the treatment of both major forms
      of diabetes, foremost among them beta cell replacement therapy. This is one of a
      series of commentaries under the banner '50 years forward', giving personal
      opinions on future perspectives in diabetes, to celebrate the 50th anniversary of
      Diabetologia (1965-2015).

PMID- 25957777
TI  - Are the metabolic changes of pregnancy reversible in the first year postpartum?
AB  - AIMS/HYPOTHESIS: Maternal metabolic alterations are essential to achieve healthy
      pregnancy outcomes, but increasing maternal parity may be associated with long
      term metabolic dysfunction risk. As existing data are limited by study design,
      our aim was to employ robust metabolic measures to determine whether or not
      physiological pregnancy alterations in maternal metabolic function persist at 1
      year postpartum. METHODS: We evaluated 21 healthy women, of whom 11 had an
      interval pregnancy (IP) and assessment at preconception, during pregnancy and 1
      year postpartum, and 10 had no IP and assessment at baseline and a 1 year
      interval. Assessment measures included body composition, insulin sensitivity and
      response, and basal metabolic rate. For each measure, IP vs no IP and time
      intervals within each group were compared using nonparametric analyses, reporting
      median (IQR). RESULTS: IP and no IP women were similar at enrolment, and no IP
      women had similar metabolic profiles at enrolment and the 1 year interval. IP
      women exhibited expected metabolic changes during pregnancy compared with
      preconception. In IP women, preconception and postpartum measures, including fat
      mass (20.7 [13.7-37.4] kg vs 18.4 [13.8-41.3] kg; p = 0.2), total insulin
      response (AUC 11,459 [9,230-13,696] pmol/ml * min vs 11,522 [5,882-17,404]
      pmol/ml * min; p = 0.9), insulin sensitivity (0.12 [0.06-0.13] mg [kg fat-free
      mass (FFM)](-1) min(-1) vs 0.11 [0.10-0.15] mg [kg FFM](-1) min(-1); p = 0.1) and
      basal metabolic rate (0.092 [0.092-0.105] kJ min(-1) FFM vs 0.096 [0.088-0.096]
      kJ min(-1) FFM; p = 0.5), were similar. CONCLUSIONS/INTERPRETATION: Our findings
      suggest pregnancy might not irreversibly alter maternal metabolic profile,
      measured at preconception through to 1 year postpartum. This result might be
      explained by a return to pre-pregnancy weight.

PMID- 25957778
TI  - Easy preparation of enantiomerically enriched heteroaromatic alcohols through
      lipase-catalyzed acylation with succinic anhydride under unconventional
      activation.
AB  - This study reports the lipase-catalyzed resolution of heteroaromatic secondary
      alcohols by succinic anhydride under different activation conditions by
      convenient procedure with succinic anhydride. The effects of succinic anhydride
      and the nature of the heteroatom are discussed in standard conditions in the
      kinetic resolution with lipases. The results recorded under microwave activation
      and ultrasonication is compared. (R)-4-chromanol was obtained in optically pure
      form (ee > 99%) with a high selectivity E > 200 by Pseudomonas cepacia lipase
      (PCL) in diethyl ether, using microwave radiation and under ultrasonication. The
      reaction time is reduced compared to the conventional heating with a better
      control of the selectivity of the lipase PCL. A significant effect of the nature
      of the heteroatoms on the reactivity and selectivity of the lipase with succinic
      anhydride has been disclosed, regardless the conditions of activation. This
      method proved to be clean, fast, interesting alternative, and facilitates the use
      of a cyclic anhydride, by microwave or ultrasound especially with secondary
      alcohols. The process is a valuable prerequisite for the preparative scale
      production of enantiomerically heteroaromatic alcohols in sustainable chemistry.

PMID- 25957779
TI  - A retrospective analysis of dentofacial deformities and orthognathic surgeries
      using the index of orthognathic functional treatment need (IOFTN).
AB  - OBJECTIVES: To assess the functional needs of orthognathic cases treated in
      Northampton General Hospital using the index of orthognathic functional treatment
      need (IOFTN). MATERIALS AND METHODS: A retrospective study was conducted on 78
      subjects (54 female and 24 males, 10-54 years, mean (SD) age=21.88 (6.98) years)
      who had orthognatic surgery in Northampton General Hospital or were in
      preparation for it (5 case). The sample represents a period between February 1997
      and December 2014. The components of IOFTN and Dental Health Component (DHC) of
      the Index of Orthodontic Treatment Need (IOTN) as well as Malocclusion type were
      recorded. RESULTS: Class III malocclusion/skeletal pattern was the most prevalent
      type (approximately 49%). There were 1, 36, 3, and 38 subjects with Class I,
      Class II Division I, Class II Division II, and Class III malocclusions,
      respectively. In terms of sagittal skeletal relationship, there were 2, 37, and
      39 subjects with Class I, Class II, and Class III skeletal bases, respectively.
      The most prevalent IOFTN score in our sample was the 5.2 (29.5%), followed by 5.3
      (15.5%), 4.2 (13%), 4.3 (11.5%). Overall, 92.3% were classified as in great and
      very great functional needs according to the IOFTN. Similarly, 84.6% scored as
      grade 4 or 5, according to the IOTN (DHC). The bimaxillary type osteotomy was the
      most prevalent type (61.5%). CONCLUSIONS: Using IOFTN, 92.3% of our sample were
      classified as having great and very great functional needs. IOFTN is a simple and
      reliable tool to identify patients in need of orthognathic surgery and can be
      used in resource allocation for patients with highest functional needs.

PMID- 25957780
TI  - Plastic bronchitis arising from solitary influenza B infection: A report of two
      cases in children.
AB  - Plastic bronchitis (PB) is characterized by thick, inspissated, tracheobronchial
      casts. It is classified as either inflammatory or acellular based on the content
      of the endobronchial casts. PB has never been reported in a healthy child with
      solitary influenza B infection. This study is a retrospective case series of two
      children who presented to our institution in acute respiratory distress.
      Emergency rigid bronchoscopy was performed with extraction of casts from the L
      mainstem bronchus in both patients. Influenza B was the only isolate identified.
      In otherwise healthy children with respiratory distress, influenza B-mediated
      inflammatory PB must be considered in the differential diagnosis. 

PMID- 25957782
TI  - Molecular subtypes, stem cells and heterogeneity: Implications for personalised
      therapy in glioma.
AB  - We discuss a number of recent developments that have led to new concepts
      regarding the biology of gliomas. Collective tissue banking, large-scale genomic,
      transcriptomic and methylomic expression profiling, and discoveries such as
      isocitrate dehydrogenase gene mutation and the C-phosphate-G island methylation
      phenotype have improved glioma classification schemes. Furthermore, the discovery
      of glioma stem cells has both enhanced and complicated our understanding. Gene
      signatures describing a proneural versus mesenchymal subtype within glioblastoma
      multiforme is reflected in both parental tumour as well as glioma stem cells and
      correlates with differential prognosis and response to radiation and
      chemotherapy. Finally, we discuss how these factors integrate with the known
      heterogeneity within brain cancers and the implications of this for the
      development of personalised therapy. 

PMID- 25957781
TI  - Genome-wide mapping of histone H3 lysine 4 trimethylation in Eucalyptus grandis
      developing xylem.
AB  - BACKGROUND: Histone modifications play an integral role in plant development, but
      have been poorly studied in woody plants. Investigating chromatin organization in
      wood-forming tissue and its role in regulating gene expression allows us to
      understand the mechanisms underlying cellular differentiation during xylogenesis
      (wood formation) and identify novel functional regions in plant genomes. However,
      woody tissue poses unique challenges for using high-throughput chromatin
      immunoprecipitation (ChIP) techniques for studying genome-wide histone
      modifications in vivo. We investigated the role of the modified histone H3K4me3
      (trimethylated lysine 4 of histone H3) in gene expression during the early stages
      of wood formation using ChIP-seq in Eucalyptus grandis, a woody biomass model.
      RESULTS: Plant chromatin fixation and isolation protocols were optimized for
      developing xylem tissue collected from field-grown E. grandis trees. A "nano-ChIP
      seq" procedure was employed for ChIP DNA amplification. Over 9 million H3K4me3
      ChIP-seq and 18 million control paired-end reads were mapped to the E. grandis
      reference genome for peak-calling using Model-based Analysis of ChIP-Seq. The
      12,177 significant H3K4me3 peaks identified covered ~1.5% of the genome and
      overlapped some 9,623 protein-coding genes and 38 noncoding RNAs. H3K4me3 library
      coverage, peaking ~600 - 700 bp downstream of the transcription start site, was
      highly correlated with gene expression levels measured with RNA-seq. Overall,
      H3K4me3-enriched genes tended to be less tissue-specific than unenriched genes
      and were overrepresented for general cellular metabolism and development gene
      ontology terms. Relative expression of H3K4me3-enriched genes in developing
      secondary xylem was higher than unenriched genes, however, and highly expressed
      secondary cell wall-related genes were enriched for H3K4me3 as validated using
      ChIP-qPCR. CONCLUSIONS: In this first genome-wide analysis of a modified histone
      in a woody tissue, we optimized a ChIP-seq procedure suitable for field-collected
      samples. In developing E. grandis xylem, H3K4me3 enrichment is an indicator of
      active transcription, consistent with its known role in sustaining pre-initiation
      complex formation in yeast. The H3K4me3 ChIP-seq data from this study paves the
      way to understanding the chromatin landscape and epigenomic architecture of
      xylogenesis in plants, and complements RNA-seq evidence of gene expression for
      the future improvement of the E. grandis genome annotation.

PMID- 25957783
TI  - Xanthomatous hypophysitis.
AB  - We present a 69-year-old woman who presented with chronic headaches and was found
      to have a pituitary mass on MRI, which was biopsied and said to be lymphocytic
      hypophysitis. The woman was placed on prednisone and followed with routine eye
      examinations. Two years later, the lesion gradually increased in size and the
      woman developed a decrease in peripheral vision in the right eye. An MRI showed
      abutment of the right optic nerve by the mass. A repeat endoscopic
      transsphenoidal biopsy/resection of the pituitary lesion was performed.
      Histopathological analysis of the specimen was consistent with diagnosis of
      xanthomatous hypophysitis (XH). XH is an inflammatory disorder of the pituitary
      gland characterized by an infiltration of lipid-laden histiocytes, also known as
      xanthoma cells. The mass was biopsied and a diagnosis of lymphocytic hypophysitis
      was made. The woman reported improved visual acuity and peripheral vision
      postoperatively. One year after the second resection, her visual symptoms
      worsened. Repeat MRI revealed expansion of the residual pituitary tissue. She was
      referred to the radiation oncology department for external beam radiation therapy
      and was placed on a maintenance dose of steroids. Since undergoing radiation
      therapy, her vision has improved slightly and her 3month MRI revealed stable
      lesion size. This woman illustrates a rare pituitary pathology presented with a
      literature review of published patients describing xanthomatous hypophysitis. A
      discussion of the clinical presentation, epidemiology, etiology, diagnosis,
      histology and treatment is provided. 

PMID- 25957784
TI  - Impact of neo-adjuvant Sorafenib treatment on liver transplantation in HCC
      patients - a prospective, randomized, double-blind, phase III trial.
AB  - BACKGROUND: Liver Transplantation (LT) is treatment of choice for patients with
      hepatocellular carcinoma (HCC) within MILAN Criteria. Tumour progression and
      subsequent dropout from waiting list have significant impact on the survival.
      Transarterial chemoembolization (TACE) controls tumour growth in the treated HCC
      nodule, however, the risk of tumour development in the untreated liver is
      increased by simultaneous release of neo-angiogenic factors. Due to its anti
      angiogenic effects, Sorafenib delays the progression of HCC. Aim of this study
      was to determine whether combination of TACE and Sorafenib improves tumour
      control in HCC patients on waiting list for LT. METHODS: Fifty patients were
      randomly assigned on a 1:1 ratio in double-blinded fashion at four centers in
      Germany and treated with TACE plus either Sorafenib (n = 24) or placebo (n = 26).
      The end of treatment was development of progressive disease according to mRECIST
      criteria or LT. The primary endpoint of the trial was the Time-to-Progression
      (TTP). Other efficacy endpoints were Tumour Response, Progression-free Survival
      (PFS), and Time-to-LT (TTLT). RESULTS: The median time of treatment was 125 days
      with Sorafenib and 171 days with the placebo. Fourteen patients (seven from each
      group) developed tumour progression during the course of the study period. The
      Hazard Ratio of TTP was 1.106 (95% CI: 0.387, 3.162). The results of the
      Objective Response Rate, Disease Control Rate, PFS, and TTLT were comparable in
      both groups. The incidence of AEs was comparable in the placebo group (n = 23,
      92%) and in the Sorafenib group (n = 23, 96%). Twelve patients (50%) on Sorafenib
      and four patients (16%) on placebo experienced severe treatment-related AEs.
      CONCLUSION: The TTP is similar after neo-adjuvant treatment with TACE and
      Sorafenib before LT compared to TACE and placebo. The Tumour Response, PFS, and
      TTLT were comparable. The safety profile of the Sorafenib group was similar to
      that of the placebo group. TRIAL REGISTRATION: ISRCTN24081794.

PMID- 25957786
TI  - Strategies to reduce water stress in Euro-Mediterranean river basins.
AB  - A portfolio of water management strategies now exists to contribute to reach
      water demand and supply targets. Among them, integrated water resource management
      has a large potential for reducing water disagreement in water scarcity regions.
      Many of the strategies are based on well tested choices and technical know-how,
      with proven benefits for users and environment. This paper considers water
      management practices that may contribute to reduce disagreement in water scarcity
      areas, evaluating the management alternatives in the Mediterranean basins of
      Europe, a region that exemplifies other water scarcity regions in the world.
      First, we use a model to compute water availability taking into account water
      management, temporal heterogeneity, spatial heterogeneity and policy options, and
      then apply this model across 396 river basins. Second, we use a wedge approach to
      illustrate policy choices for selected river basins: Thrace (Greece),
      Guadalquivir, Ebro, Tagus and Duero (Spain), Po (Italy) and Rhone (France). At
      the wide geographical level, the results show the multi-determinant complexities
      of climate change impacts and adaptation measures and the geographic nature of
      water resources and vulnerability metrics. At the local level, the results show
      that optimisation of water management is the dominating strategy for defining
      adaptation pathways. Results also show great sensitivity to ecological flow
      provision, suggesting that better attention should be paid to defining methods to
      estimate minimum ecological flows in water scarcity regions. For all scales,
      average water resource vulnerability computed by traditional vulnerability
      indicators may not be the most appropriate measure to inform climate change
      adaptation policy. This has large implications to applied water resource studies
      aiming to derive policy choices, and it is especially interesting in basins
      facing water scarcity. Our research aims to contribute to shape realistic water
      management options at the regional level and therefore provide information to
      climate change, agricultural and water policies. 

PMID- 25957785
TI  - Transdisciplinary synthesis for ecosystem science, policy and management: The
      Australian experience.
AB  - Mitigating the environmental effects of global population growth, climatic change
      and increasing socio-ecological complexity is a daunting challenge. To tackle
      this requires synthesis: the integration of disparate information to generate
      novel insights from heterogeneous, complex situations where there are diverse
      perspectives. Since 1995, a structured approach to inter-, multi- and trans
      disciplinary(1) collaboration around big science questions has been supported
      through synthesis centres around the world. These centres are finding an
      expanding role due to ever-accumulating data and the need for more and better
      opportunities to develop transdisciplinary and holistic approaches to solve real
      world problems. The Australian Centre for Ecological Analysis and Synthesis
      (ACEAS <http://www.aceas.org.au>) has been the pioneering ecosystem science
      synthesis centre in the Southern Hemisphere. Such centres provide analysis and
      synthesis opportunities for time-pressed scientists, policy-makers and managers.
      They provide the scientific and organisational environs for virtual and face-to
      face engagement, impetus for integration, data and methodological support, and
      innovative ways to deliver synthesis products. We detail the contribution, role
      and value of synthesis using ACEAS to exemplify the capacity for synthesis
      centres to facilitate trans-organisational, transdisciplinary synthesis. We
      compare ACEAS to other international synthesis centres, and describe how it
      facilitated project teams and its objective of linking natural resource science
      to policy to management. Scientists and managers were brought together to
      actively collaborate in multi-institutional, cross-sectoral and transdisciplinary
      research on contemporary ecological problems. The teams analysed, integrated and
      synthesised existing data to co-develop solution-oriented publications and
      management recommendations that might otherwise not have been produced. We
      identify key outcomes of some ACEAS working groups which used synthesis to tackle
      important ecosystem challenges. We also examine the barriers and enablers to
      synthesis, so that risks can be minimised and successful outcomes maximised. We
      argue that synthesis centres have a crucial role in developing, communicating and
      using synthetic transdisciplinary research. 

PMID- 25957788
TI  - Perceived discontinuities and continuities in transdisciplinary scientific
      working groups.
AB  - We examine the DataONE (Data Observation Network for Earth) project, a
      transdisciplinary organization tasked with creating a cyberinfrastructure
      platform to ensure preservation of and access to environmental science and
      biological science data. Its objective was a difficult one to achieve, requiring
      innovative solutions. The DataONE project used a working group structure to
      organize its members. We use organizational discontinuity theory as our lens to
      understand the factors associated with success in such projects. Based on
      quantitative and qualitative data collected from DataONE members, we offer
      recommendations for the use of working groups in transdisciplinary synthesis.
      Recommendations include welcome diverse opinions and world views, establish
      shared communication practices, schedule periodic synchronous face-to-face
      meetings, and ensure the active participation of bridge builders or knowledge
      brokers such as librarians who know how to ask questions about disciplines not
      their own. 

PMID- 25957787
TI  - Identifying sources of ozone to three rural locations in Nevada, USA, using
      ancillary gas pollutants, aerosol chemistry, and mercury.
AB  - Ozone (O3) is a secondary air pollutant of long standing and increasing concern
      for environmental and human health, and as such, the US Environmental Protection
      Agency will revise the National Ambient Air Quality Standard of 75 ppbv to <= 70
      ppbv. Long term measurements at the Great Basin National Park (GBNP) indicate
      that O3 in remote areas of Nevada will exceed a revised standard. As part of the
      Nevada Rural Ozone Initiative, measurements of O3 and other air pollutants were
      made at 3 remote sites between February 2012 and March 2014, GBNP, Paradise
      Valley (PAVA), and Echo Peak (ECHO). Exceptionally high concentrations of each
      air pollutant were defined relative to each site as mixing ratios that exceeded
      the 90th percentile of all hourly data. Case studies were analyzed for all
      periods during which mean daily O3 exceeded the 90th percentile concurrently with
      a maximum 8-h average (MDA8) O3 that was "exceptionally high" for the site (65
      ppbv at PAVA, 70 ppbv at ECHO and GBNP), and of potential regulatory
      significance. An MDA8 >= 65 ppbv occurred only five times at PAVA, whereas this
      occurred on 49 and 65 days at GBNP and ECHO, respectively. The overall
      correlation between O3 and other pollutants was poor, consistent with the large
      distance from significant primary emission sources. Mean CO at these locations
      exceeded concentrations reported for background sites in 2000. Trajectory
      residence time calculations and air pollutant concentrations indicate that
      exceedances at GBNP and ECHO were promoted by air masses originating from
      multiple sources, including wildfires, transport of pollution from southern
      California and the marine boundary layer, and transport of Asian pollution
      plumes. Results indicate that the State of Nevada will exceed a revised O3
      standard due to sources that are beyond their control.

PMID- 25957789
TI  - Increased risk of second primary malignancies following uterine cancer: a
      population-based study in Taiwan over a 30-year period.
AB  - BACKGROUND: Previous studies assessing second primary malignancies (SPMs) after
      uterine cancer have been conducted in Western populations with conflicting
      results. This study aimed to define the incidence and risk of SPMs in Taiwanese
      patients with an initial diagnosis of uterine cancer. METHODS: Using population
      based data from the Taiwan Cancer Registry for the period 1979-2008, we
      quantified standardized incidence ratios (SIRs) among 11,571 women with an
      initial diagnosis of uterine cancer. RESULTS: Among the 11,571 women, 555 (4.80%)
      developed at least one SPM during 69,987 person-years of follow-up. There was a
      71% increased risk of SPM following uterine cancer (SIR=1.71, 95% CI, 1.57-1.86),
      with higher risks in the vagina/vulva (SIR=9.06), small intestine (SIR=8.45),
      ovary (SIR=4.15), urinary bladder (SIR=2.31), kidney (SIR=2.24), colorectum
      (SIR=2.24), lung (SIR=1.96), and breast (SIR=1.43). The risk of SPM was found to
      be the highest within the first 5 years after diagnosis of uterine cancer, with
      surveillance bias possibly contributing to the extremely high risk observed in
      the first follow-up year. The overall risk and pattern of SPM development
      observed in this study differed from those previously reported in Western
      populations, possibly because of the methodology and shorter follow-up period
      employed in this study. The cumulative incidence of SPMs was significantly higher
      in older patients (>=50 years) than in younger patients (P<0.001). CONCLUSIONS:
      To our knowledge, this is the first study in an Asian population to report 71%
      increased risk in SPMs in women previously diagnosed with uterine cancer. A
      younger age at diagnosis of uterine cancer conferred an increased risk of second
      malignancies, and SPMs worsened survivorship in patients who survived uterine
      cancer.

PMID- 25957790
TI  - Differential effects of duration of sleep fragmentation on spatial learning and
      synaptic plasticity in pubertal mice.
AB  - STUDY OBJECTIVE: To examine the differential effects of acute and chronic sleep
      fragmentation (SF) on spatial learning and memory, and hippocampal long-term
      potentiation (LTP) in pubertal mice. METHODS: Two studies were performed during
      which adolescent C57/Bl6 mice were subjected to acute-SF 24h a day * 3 days or
      chronic-SF for 12h a day * 2 weeks using a programmable rotating lever that
      provides tactile stimulus with controls housed in similar cages. Spatial learning
      and memory was examined using the Morris water maze, and long-term potentiation
      (LTP) was evaluated after stimulation of Schaffer collaterals in CA1 hippocampus
      post SF. Actigraphy was used during the period of SF to monitor rest-activity
      patterns. Electroencephalographic (EEG) recordings were acquired for analysis of
      vigilance state patterns and delta-power. Serum corticosterone was measured to
      assess stress levels. RESULTS: Acute-SF via tactile stimulation negatively
      impacted spatial learning, as well as LTP maintenance, compared to controls with
      no tactile stimulation. While actigraphy showed significantly increased motor
      activity during SF in both groups, EEG data indicated that overall sleep
      efficiency did not differ between baseline and SF days, but significant increases
      in number of wakeful bouts and decreases in average NREM and REM bout lengths
      were seen during lights-on. Acute sleep fragmentation did not impact
      corticosterone levels. CONCLUSIONS: The current results indicate that, during
      development in pubertal mice, acute-SF for 24h a day * 3 days negatively impacted
      spatial learning and synaptic plasticity. Further studies are needed to determine
      if any inherent long-term homeostatic mechanisms in the adolescent brain afford
      greater resistance to the deleterious effects of chronic-SF.

PMID- 25957791
TI  - Role of the planar cell polarity pathway in regulating ectopic hair cell-like
      cells induced by Math1 and testosterone treatment.
AB  - Planar cell polarity (PCP) signaling regulates cochlear extension and coordinates
      orientation of sensory hair cells in the inner ear. Retroviral-mediated
      introduction of the Math1 transcription factor leads to the transdifferentiation
      of some mature supporting cells into hair cells. Testosterone, a gonadal sex
      steroid hormone, is associated with neuroprotection and regeneration in Central
      Nervous System (CNS) development. Experiments were performed in vitro using Ad5
      EGFP-Math1/Ad5-Math1 in neonatal mouse cochleas. Establishment of ectopic hair
      cell like cell(HCLC) polarity in the lesser epithelial ridge (LER) with or
      without testosterone-3-(O-carboxymethyl) oxime bovine serum albumin (testosterone
      BSA) treatment was investigated to determine the role of the PCP pathway in
      regulating ectopic regenerated (HCLCs) through induction by Math1 and
      testosterone treatment. After Math1 infection, new ectopic regenerated HCLCs were
      detected in the LER. After the HCLCs developed actin-rich stereocilia, the basal
      bodies moved from the center to the distal side. Moreover, the narrower, non
      sensory LER region meant that the convergent extension (CE) was also established
      after transfection with Math1. After 9 days of in vitro testosterone-BSA
      treatment, more Edu(+), Sox2(+), and HCLC cells were observed in the LER with an
      accompanying downregulation of E-cadherin. Interestingly, the CE of the Ad5-EGFP
      math1 treated LER is altered, but the intrinsic cellular polarity of the HCLCs is
      not obviously changed. In summary, our results indicate that PCP signaling is
      involved in the development of ectopic HCLCs and the CE of the ectopic sensory
      region is altered by testosterone-BSA through downregulation of cell-cell
      adhesion. Testosterone-BSA and Math1 treatment could promote an increase in HCLCs
      in the LER through proliferation and transdifferentiation. 

PMID- 25957792
TI  - The accumulation of brain water-free sodium is associated with ischemic damage
      independent of the blood pressure in female rats.
AB  - Estrogen deficiency worsens ischemic stroke outcomes. In ovariectomized (OVX(+))
      rats fed a high-salt diet (HSD), an increase in the body Na(+)/water ratio, which
      characterizes water-free Na(+) accumulation, was associated with detrimental
      vascular effects independent of the blood pressure (BP). We hypothesized that an
      increase in brain water-free Na(+) accumulation is associated with ischemic brain
      damage in OVX(+)/HSD rats. To test our hypothesis we divided female Wistar rats
      into 4 groups, OVX(+) and OVX(-) rats fed HSD or a normal diet (ND), and
      subjected them to transient cerebral ischemia. The brain Na(+)/water ratio was
      increased even in OVX(+)/ND rats and augmented in OVX(+)/HSD rats. The increase
      in the brain Na(+)/water ratio was positively correlated with expansion of the
      cortical infarct volume without affecting the BP. Interestingly, OVX(+) was
      associated with the decreased expression of ATP1alpha3, a subtype of the Na(+)
      efflux pump. HSD increased the expression of brain Na(+) influx-related molecules
      and the mineralocorticoid receptor (MR). The pretreatment of OVX(+)/HSD rats with
      the MR antagonist eplerenone reduced brain water-free Na(+) accumulation, up
      regulated ATP1alpha3, down-regulated MR, and reduced the cortical infarct volume.
      Our findings show that the increase in the brain Na(+)/water ratio elicited by
      estrogen deficiency or HSD is associated with ischemic brain damage BP
      independently, suggesting the importance of regulating the accumulation of brain
      water-free Na(+). The up-regulation of ATP1alpha3 and the down-regulation of MR
      may provide a promising therapeutic strategy to attenuate ischemic brain damage
      in postmenopausal women. 

PMID- 25957793
TI  - The impact of lipid-based nutrient supplementation on anti-malarial antibodies in
      pregnant women in a randomized controlled trial.
AB  - BACKGROUND: Malaria and undernutrition frequently coexist, especially in pregnant
      women and young children. Nutrient supplementation of these vulnerable groups
      might reduce their susceptibility to malaria by improving immunity. METHODS:
      Antibody immunity to antigens expressed by a placental-binding parasite isolate,
      a non-placental binding parasite isolate, merozoites and schizonts at enrolment
      (before 20 gestation weeks) and at 36 gestation weeks were measured in 1,009
      Malawian pregnant women receiving a daily lipid-based nutrient supplement,
      multiple micronutrients or iron and folic acid, who were participants in a
      randomized clinical trial assessing the effects of nutrient supplementation on
      pregnancy outcomes and child development (registration ID: NCT01239693). RESULTS:
      Antibodies to placental-binding isolates significantly increased while antibodies
      to most merozoite antigens declined over pregnancy. Overall, after adjustment for
      covariates, the type of supplementation did not influence antibody levels at 36
      gestation weeks or the rate of change in antibody levels from enrolment to 36
      weeks. A negative association between maternal body mass index and opsonizing
      antibodies to placental-binding antigens (coefficient (95% CI) -1.04 (-1.84, 
      0.24), was observed. Similarly, women with higher socioeconomic status had
      significantly lower IgG and opsonizing antibodies to placental-binding antigens.
      Neither of these associations was significantly influenced by the supplementation
      type. CONCLUSIONS: In the current cohort nutrient supplementation did not affect
      anti-malarial antibody responses, but poor and undernourished mothers should be a
      priority group in future trials.

PMID- 25957794
TI  - A hyper-connected but less efficient small-world network in the substance
      dependent brain.
AB  - BACKGROUND: The functional interconnections of the addicted brain may differ from
      the non-addicted population in important ways, but prioranalytic approaches were
      usually limited to the study of connections between a few number of selected
      brain regions. Recent approaches enable examination of the vast functional
      interactions within the entire brain, the functional connectome (FCM). The
      purpose of this study was to characterize FCM alterations in addiction using
      resting state functional Magnetic Resonance Imaging (rsfMRI) and to assess their
      relations to addiction-related symptoms. METHODS: rsfMRI data were acquired from
      20 chronic polydrug users whose primary diagnosis was cocaine dependence (DRUG)
      and 19 age-matched non-drug using healthy controls (CTL). FCM was assessed using
      graph theoretical analysis. RESULTS: Among the assessed 90 brain subdivisions,
      DRUG showed stronger functional connectivity. After controlling functional
      connectivity difference and the resultant network density, DRUG showed reduced
      communication efficiency and reduced small-worldness. CONCLUSIONS: The increased
      connection strength in drug users' brain suggests an elevated dynamic resting
      state that may enable a rapid, semi-automatic, execution of behaviors directed
      toward drug-related goals.The reduced FCM communication efficiency and reduced
      small-worldness suggest a loss of normal inter-regional communications and
      topology features that makes it difficult to inhibit the drug seeking behavior.

PMID- 25957795
TI  - The periovulatory endocrine milieu affects the uterine redox environment in beef
      cows.
AB  - BACKGROUND: In cattle, recent studies have shown positive associations between
      pre-ovulatory concentrations of estradiol (E2), progesterone (P4) at early
      diestrus and fertility. However, information on cellular and molecular mechanisms
      through which sex steroids regulate uterine function to support early pregnancy
      is lacking. Based on endometrial transcriptome data, objective was to compare
      function of the redox system in the bovine uterus in response to different
      periovulatory endocrine milieus. METHODS: We employed an animal model to control
      growth of the pre-ovulatory follicle and subsequent corpus luteum (CL). The large
      follicle-large CL group (LF-LCL, N=42) presented greater levels of E2 on the day
      of GnRH treatment (D0; 2.94 vs. 1.27 pg/mL; P=0.0007) and P4 at slaughter on D7
      (3.71 vs. 2.62 ng/mL, P=0.01), compared with the small follicle-small CL group
      (SF-SCL, N=41). Endometrium and uterine washings (N=9, per group) were collected
      for analyses of variables associated with the uterine redox system. RESULTS: The
      SF-SCL group had lower endometrial catalase (0.5 vs. 0.79 U/mg protein, P<0.001)
      and glutathione peroxidase (GPx; 2.0 vs. 2.43 nmol beta-nicotinamide adenine
      dinucleotide phosphate reduced/min/mg protein, P=0.04) activity, as well as
      higher lipid peroxidation (28.5 vs. 17.43 nmol malondialdehyde/mg of protein,
      P<0.001) and superoxide dismutase (SOD) activity (44.77 vs. 37.76 U; P=0.04).
      There were no differences in the endometrial reactive species (RS) or glutathione
      (GSH) concentrations between the groups. The uterine washing samples showed no
      differences in the concentrations of RS or GSH or in total SOD activity (P>0.1).
      Additionally, catalase, GPx4, SOD1 and SOD2 gene expression was lower in the SF
      SCL group than in the LF-LCL group. CONCLUSIONS: We concluded that the
      intrauterine environment of cows from the LF-LCL group exhibited higher
      antioxidant activity than that of the cows from the SF-SCL group. We speculate
      that uterine receptivity and fertility are associated with an optimal redox
      environment, such as that present in the animals in the LF-LCL group.

PMID- 25957796
TI  - Continuous flow left ventricular assist device implantation concomitant with
      aortic arch replacement and aortic valve closure in a patient with end-stage
      heart failure associated with bicuspid aortic valve.
AB  - Left ventricular assist device (LVAD) implantation has become an established
      treatment for patients with end-stage heart failure as a bridge to cardiac
      transplantation. During LVAD implantation, some patients require concomitant
      surgeries, including tricuspid valve repair, aortic valve repair or replacement,
      and patent foramen ovale closure. However, concomitant aortic surgeries are rare
      in patients requiring LVAD implantation. We successfully performed total arch
      replacement with an open distal technique, aortic valve closure, and continuous
      flow LVAD implantation simultaneously. 

PMID- 25957797
TI  - BRAF Immunohistochemistry Using Clone VE1 is Strongly Concordant with BRAF(V600E)
      Mutation Test in Papillary Thyroid Carcinoma.
AB  - The aim of this study was to investigate the concordance between BRAF(V600E)
      mutation test and immunohistochemistry (IHC) and determine the diagnostic
      accuracy of IHC for papillary thyroid carcinoma (PTC) through a systematic
      review, meta-analysis, and diagnostic test accuracy review. The current
      systematic review and meta-analysis included 1141 PTCs in 11 eligible studies. We
      investigated the concordance rate and performed subgroup analysis using tissue
      and cytologic samples. Diagnostic test accuracy review was conducted and
      calculated using the value of area under curve (AUC) on the summary receiver
      operating characteristic (SROC) curve. The positive rate of BRAF IHC was 79.1%
      (903 of 1141 cases), and the BRAF(V600E) mutation was found in 76.6% (874 of 1141
      cases). The concordance rates were 0.921 (95% confidence interval (CI) 0.877
      0.950) and 0.894 (95% CI 0.801-0.946) in IHC positive and negative subgroups,
      respectively. In the diagnostic test accuracy review, the pooled sensitivity and
      specificity were 0.97 (95% CI 0.95-0.98) and 0.78 (95% CI 0.72-0.83). The value
      of AUC on SROC curve was 0.983, and diagnostic odds ratio was 164.28 (95% CI
      57.69-467.80). Our results showed that BRAF IHC was strongly concordant with BRAF
      mutation test and had high diagnostic accuracy in BRAF mutation analysis of PTC.

PMID- 25957798
TI  - Cognitive enhancing agents in schizophrenia and bipolar disorder.
AB  - Cognitive dysfunction is a core feature of schizophrenia and is also present in
      bipolar disorder (BD). Whereas decreased intelligence precedes the onset of
      psychosis in schizophrenia and remains relatively stable thereafter; high
      intelligence is a risk factor for bipolar illness but cognitive function
      decreases after onset of symptoms. While in schizophrenia, many studies have been
      conducted on the development of cognitive enhancing agents; in BD such studies
      are almost non-existent. This review focuses on the pharmacological agents with
      putative effects on cognition in both schizophrenia and bipolar illness;
      specifically agents targeting the dopaminergic, cholinergic and glutamatergic
      neurotransmitter pathways in schizophrenia and the cognitive effects of lithium,
      anticonvulsants and antipsychotics in BD. In the final analysis we conclude that
      cognitive enhancing agents have not yet been produced convincingly for
      schizophrenia and have hardly been studied in BD. Importantly, studies should
      focus on other phases of the illness. To be able to treat cognitive deficits
      effectively in schizophrenia, patients in the very early stages of the illness,
      or even before - in the ultra-high risk stages - should be targeted. In contrast,
      cognitive deficits occur later in BD, and therefore drugs should be tested in BD
      after the onset of illness. Hopefully, we will then find effective drugs for the
      incapacitating effects of cognitive deficits in these patients. 

PMID- 25957799
TI  - CNS biomarkers: Potential from a regulatory perspective: Case study - Focus in
      low hippocampus volume as a biomarker measured by MRI.
AB  - Our objectives are to describe the procedure for qualification advice and opinion
      from EU regulators on the use of novel methodologies in drug development, the key
      stakeholders involved and the evidence requirements for qualification opinion. We
      present a case study of the request from the Coalition Against Major Disease
      (CAMD) Consortium of the Critical Path (C-Path) Institute for EU regulators'
      qualification opinion on the use of low hippocampal volume as a biomarker for
      population enrichment in clinical trials of novel drugs in Alzheimer's disease
      (AD). We discuss the main concerns from the regulators, data analysis requests
      and guidance during the qualification. EU regulators concluded that low
      hippocampal volume, measured by vMRI and considered as a dichotomized variable
      (low volume or not), appears to help enriching recruitment into clinical trials
      aimed at studying drugs that potentially slow the progression of the pre-dementia
      stage of AD. The biomarker qualification procedure is a dynamic process in which
      pharmaceutical companies and research consortia can submit further data to update
      the qualifications and improve the predictive value of the biomarkers. 

PMID- 25957800
TI  - A hydrophobic interaction chromatography strategy for purification of inactivated
      foot-and-mouth disease virus.
AB  - A purification scheme based on hydrophobic interaction chromatography was
      developed to separate inactivated foot-and-mouth disease virus (FMDV) from crude
      supernatant. About 92% recovery and 8.8-fold purification were achieved on Butyl
      Sepharose 4 FF. Further purification on Superdex 200 resulted in another 29-fold
      purification, with 92% recovery. The columns were coupled through an intermediate
      ultrafiltration unit to concentrate the virus. The entire process was completed
      in about 3.5h, with 75% final FMDV recovery, and 247-fold purification. The final
      product had purity above 98%, with over 99.5% of host cell DNA removed. High
      performance size exclusion chromatography (HPSEC), Western blot, dynamic light
      scattering (DLS), and transmission electron microscopy (TEM) indicated that the
      purified virus contained the required antigen, and was structurally intact with a
      spherical shape and a particle size of 28 nm.

PMID- 25957801
TI  - Healthcare providers' perspectives on the social reintegration of patients after
      surgical fistula repair in the eastern Democratic Republic of Congo.
AB  - OBJECTIVE: To understand perspectives of local health providers on the social
      reintegration of patients who have undergone fistula repair in the eastern
      Democratic Republic of Congo. METHODS: In a qualitative study, semi-structured
      individual interviews were conducted with patient-care professionals working with
      women with fistula at HEAL Africa Hospital (Goma) and Panzi Hospital (Bukavu)
      between June and August 2011. The interviews were transcribed and themes elicited
      through manual coding. RESULTS: Overall, 41 interviews were conducted. Successful
      surgical repair was reported to be the most important factor contributing to
      patients' ability to lead a normal life by all providers. Family acceptance
      especially from the husband-was deemed crucial for reintegration by 39 (95%)
      providers, and 29 (71%) believed this acceptance was more important than the
      ability to work. Forty (98%) providers felt that, on the basis of African values,
      future childbearing was key for family acceptance. Because of poor access and the
      high cost of cesarean deliveries, 28 (68%) providers were concerned about fistula
      recurrence. CONCLUSION: Providers view postsurgical childbearing as crucial for
      social reintegration after fistula repair. However, cesarean deliveries are
      costly and often inaccessible. More work is needed to improve reproductive health
      access for women after fistula repair.

PMID- 25957802
TI  - Five-year follow-up of two types of contraceptive device fitted during elective
      cesarean delivery.
AB  - OBJECTIVE: To present follow-up data for patients fitted with a copper
      intrauterine contraceptive device (IUCD) or the levonorgestrel intrauterine
      system (IUS) during cesarean delivery. METHODS: Between March 2006 and December
      2011, a prospective study was undertaken of women who were scheduled to have a
      repeat cesarean for a singleton pregnancy and had chosen to undergo
      intraoperative fitting of an IUCD or the IUS. Participants were followed up for
      up to 5 years using transvaginal ultrasonography, clinical evaluation, and a
      questionnaire. RESULTS: Among 143 participants, 63 requested the IUCD and 80 the
      IUS. Misalignment was more common at 6 weeks with the IUS (37 [46.3%] patients)
      than with the IUCD (22 [34.9%]; P=0.06). Spontaneous expulsion occurred in the
      IUCD group only (4 [6.3%] patients). No pregnancies were reported in the IUS
      group, whereas 4 (6.3%) women with the IUCD became pregnant. CONCLUSION: Although
      misalignment of an IUCD or the IUS is fairly common after intraoperative
      insertion, the contraceptive performance and menstrual pattern are not affected.
      Therefore, there is no need to remove or replace a misaligned IUCD or IUS.

PMID- 25957803
TI  - The end is not the end: remnants of tRNA precursors live on to sponge up small
      regulatory RNAs.
AB  - Natural RNA sponges sequestering cellular noncoding RNA molecules have been found
      in diverse organisms. In this issue, Lalaouna et al. (2015) report another type
      of RNA sponge, showing that stable intermediates of bacterial tRNA processing
      control endogenous small RNAs.

PMID- 25957804
TI  - Regulating transcription traffic around DSBs.
AB  - If a double-strand break (DSB) occurs and either a DNA polymerase or RNA
      polymerase is coming along, how do we save the train? In this issue of Molecular
      Cell, Ui et al. (2015) describe a connection between an elongation factor and a
      repressive complex to prevent transcription in proximity to a DSB.

PMID- 25957806
TI  - Virus and Immune-Mediated Encephalitides: Epidemiology, Diagnosis, Treatment, and
      Prevention.
AB  - Virus encephalitis remains a major cause of acute neurological dysfunction and
      permanent disability among children worldwide. Although some disorders, such as
      measles encephalomyelitis, subacute sclerosing panencephalitis, and varicella
      zoster virus-associated neurological conditions, have largely disappeared in
      resource-rich regions because of widespread immunization programs, other
      disorders, such as herpes simplex virus encephalitis, West Nile virus-associated
      neuroinvasive disease, and nonpolio enterovirus-induced disorders of the nervous
      system, cannot be prevented. Moreover, emerging viral disorders pose new,
      potential threats to the child's nervous system. This review summarizes current
      information regarding the epidemiology of virus encephalitis, the diagnostic
      methods available to detect central nervous system infection and identify viral
      pathogens, and the available treatments. The review also describes immune
      mediated disorders, including acute disseminated encephalomyelitis and N-methyl-D
      aspartate receptor antibody encephalitis, conditions that mimic virus
      encephalitis and account for a substantial proportion of childhood encephalitis. 

PMID- 25957805
TI  - Proximal Left Anterior Descending Artery Acute Occlusion With an Unusual
      Electrocardiographic Pattern: Not Everything Is ST Elevation.

PMID- 25957807
TI  - Complete genome sequence of Bacillus pumilus W3: A strain exhibiting high laccase
      activity.
AB  - Here we report the full genome sequence of Bacillus pumilus W3, which was
      isolated from raw gallnut honey in Nandan County, Guangxi Province of China,
      showing high CotA-laccase activity. The W3 strain contains 3,745,123bp with GC
      content of 41.39%, and contains 3695 protein-coding genes, 21 rRNAs and 70 tRNAs.

PMID- 25957808
TI  - Ten advances defining sudden cardiac death.
AB  - Recent advances in the field of sudden cardiac death (SCD) include the
      recognition that 50% of SCD occurs as initial presentation of any heart disease
      and that many of these individuals may have been considered to be low risk. The
      presenting dysrhythmia in patients with cardiac arrests has changed over time
      such that pulseless electrical activity and asystole is more frequently
      encountered as compared with ventricular tachyarrhythmias. While the use of
      implantable defibrillators has been a tremendous advance in patients at risk for
      ventricular tachyarrhythmias, the use of automatic external defibrillators and
      wearable defibrillators is a recent advance that allows for potential SCD
      prevention in more patients. Finally, the area of medical genetics is an evolving
      discipline, which may enable clinicians to better individualize therapy for
      patients with genetic predispositions to cardiac dysrhythmias. 

PMID- 25957809
TI  - The continued importance of optimal medical therapy with or without
      revascularization in diabetic patients with coronary artery disease.

PMID- 25957810
TI  - Ethnobotanical survey of medicinal plants used in the Maseru district of Lesotho.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ethnobotanical knowledge in Lesotho is passed on
      orally from one generation to another. As a result it has not been well
      documented. Existing publications have relied on previous literature and are
      limited either in terms of scope or coverage. Furthermore, some of them are out
      of print. Therefore, there are gaps in the documentation of medicinal plants used
      in Lesotho. AIM OF THE STUDY: The purpose of the current study is to investigate
      common ailments in Lesotho's traditional medicine and document plants that are
      used in treating such ailments. MATERIALS AND METHODS: Interviews were conducted
      in five urban and four rural areas of the capital town of Maseru, by means of
      questionnaires to elicit information on medicinal plant use to cure common
      ailments. The informants were 20 males and seven females comprising 15
      traditional healers, 11 herbalists and one pharmacist. RESULTS: Reproductive
      ailments were found to be the most commonly treated, followed by respiratory,
      degenerative and digestive problems. A list of the 80 plants used for treating
      the common ailments is given. A total of 44 families is represented, with
      Asteraceae, Fabaceae, Asphodelaceae and Poaceae families having the highest
      number of species used for medicinal purposes. The most frequently mentioned
      medicinal plants in interviews include; Elephantorrhiza elephantina, Pentanisia
      prunelloides, Hypoxis hermerocallidea, Eriocephalus sp., Salvia runcinata,
      Scabiosa columbaria, Dicoma anomala, Morella serrata, Xysmalobium undulatum, and
      Leobordea lanceolata. Due to the high demand of medicinal plants, some species
      such as L. lanceolata, Tephrosia capensis, E. elephantina, D. anomala and P.
      prunelloides were reported as over-harvested. In some cases animal products are
      added to the medicinal plants to enhance their curative abilities. CONCLUSIONS: A
      total of 80 plants were recorded in the study as treating 38 common ailments in
      the Maseru district of Lesotho. Records of eight medicinal plants and 146 new
      medicinal uses of 34 plants that were not recorded elsewhere in literature are
      reported in the current study for the first time. The new records of medicinal
      plants used in traditional healing practices in Lesotho clearly show the need to
      document these practices, and the wealth of new knowledge gained with the current
      study reinforces the importance of extending the study to other parts of Lesotho.

PMID- 25957811
TI  - LC-MS/MS based studies on the anti-depressant effect of hypericin in the chronic
      unpredictable mild stress rat model.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: St John's Wort (Hypericum perforatum, SJW) is a
      widely used herbal medicine in western countries but also an important Uygur drug
      in China. Hypericin (HY) is the main components in SJW extracts, which is used to
      treat fatigue, weakness, and mild depression. The aim of this study was to
      investigate the anti-depression effects of HY on chronic unpredictable mild
      stress (CUMS) model rats and identify the possible mechanisms. MATERIALS AND
      METHODS: In this study, the protective effects of HY on CUMS-induced depression
      in rats were investigated by using a combination of behavioral assessments and
      urinary metabolites analysis. Urinary metabolites analyses were performed using
      LC-MS/MS in conjunction with principal components analysis (PCA) after oral
      administration of either HY or Venlafaxine (VF) for 27 days. During the procedure
      of experiment, food consumption, body weight, adrenal gland, thymus and spleen
      indices, behavior scores, sucrose consumption, and stress hormone levels were
      measured. RESULTS: Changes in the classic behavioral tests and pharmacological
      biochemical indices reflected that HY alleviated the symptoms of depression in a
      shorter period than VF, which was used as positive control for antidepression.
      Metabolites analysis of urine revealed that HY affected excitatory amino acids
      and monoamine neurotransmitter metabolites. Remarkably, urinary valine was
      increased remarkably by HY, even much higher than CUMS group. These results
      provide important mechanistic insights into the protective effects of HY against
      CUMS-induced depression and metabolic dysfunction. CONCLUSION: As the most
      important active ingredient in SJW extracts, HY possesses the better protective
      effect against CUMS-induced depression symptoms and metabolic disturbances.

PMID- 25957814
TI  - mRNA metabolism and neuronal disease.
AB  - To serve as templates for translation eukaryotic mRNAs undergo an elaborate
      processing and maturation pathway. In eukaryotes this process comprises the
      synthesis of mRNA precursors, their processing and transport to the site of
      translation and eventually their decay. During the entire life cycle, mRNAs
      interact with distinct sets of trans-acting factors that determine their fate at
      any given phase of gene expression. Recent studies have shown that mutations in
      components acting in trans on mRNAs are frequent causes of a large variety of
      different human disorders. The etiology of most of these diseases is, however,
      only poorly understood, mostly because the consequences for mRNA-metabolism are
      unclear. Here we discuss three prominent genetic diseases that fall into this
      category, namely spinal muscular atrophy (SMA), retinitis pigmentosa (RP) and X
      linked syndromic mental retardation (XLMR). Whereas SMA and RP can be directly
      linked to mRNA processing, XLMR results from mutations in the mRNA surveillance
      system. We discuss how defects in mRNA maturation and turnover might lead to the
      tissue specific defects seen in these diseases. 

PMID- 25957813
TI  - Engineering alpha4beta2 nAChRs with reduced or increased nicotine sensitivity via
      selective disruption of consensus sites in the M3-M4 cytoplasmic loop of the
      alpha4 subunit.
AB  - The alpha4beta2 neuronal nicotinic acetylcholine receptor (nAChR) plays a crucial
      role in nicotine addiction. These receptors are known to desensitize and up
      regulate after chronic nicotine exposure, but the mechanism remains unknown.
      Currently, the structure and functional role of the intracellular domains of the
      nAChR are obscure. To study the effect of subunit phosphorylation on alpha4beta2
      nAChR function and expression, eleven residues located in the M3-M4 cytoplasmic
      loop were mutated to alanine and aspartic acid. Two-electrode voltage clamp and
      125I-labeled epibatidine binding assays were performed on Xenopus oocytes to
      assess agonist activation and receptor expression. When ACh was used as an
      agonist, a decrease in receptor activation was observed for the majority of the
      mutations. When nicotine was used as an agonist, four mutations exhibited a
      statistically significant hypersensitivity to nicotine (S438D, S469A, Y576A, and
      S589A). Additionally, two mutations (S516D and T536A) that displayed normal
      activation with ACh displayed remarkable reductions in sensitivity to nicotine.
      Binding assays revealed a constitutive up-regulation in these two nicotine
      mutations with reduced nicotine sensitivity. These results suggest that consensus
      phosphorylation residues in the M3-M4 cytoplasmic loop of the alpha4 subunit play
      a crucial role in regulating alpha4beta2 nAChR agonist selectivity and functional
      expression. Furthermore, these results suggest that disruption of specific
      interactions at PKC putative consensus sites can render alpha4beta2 nAChRs almost
      insensitive to nicotine without substantial effects on normal AChR function.
      Therefore, these PKC consensus sites in the M3-M4 cytoplasmic loop of the alpha4
      nAChR subunit could be a target for smoking cessation drugs.

PMID- 25957812
TI  - Targeting histone deacetylase 6 mediates a dual anti-melanoma effect: Enhanced
      antitumor immunity and impaired cell proliferation.
AB  - The median survival for metastatic melanoma is in the realm of 8-16 months and
      there are few therapies that offer significant improvement in overall survival.
      One of the recent advances in cancer treatment focuses on epigenetic modifiers to
      alter the survivability and immunogenicity of cancer cells. Our group and others
      have previously demonstrated that pan-HDAC inhibitors induce apoptosis, cell
      cycle arrest and changes in the immunogenicity of melanoma cells. Here we
      interrogated specific HDACs which may be responsible for this effect. We found
      that both genetic abrogation and pharmacologic inhibition of HDAC6 decreases in
      vitro proliferation and induces G1 arrest of melanoma cell lines without inducing
      apoptosis. Moreover, targeting this molecule led to an important upregulation in
      the expression of tumor associated antigens and MHC class I, suggesting a
      potential improvement in the immunogenicity of these cells. Of note, this anti
      melanoma activity was operative regardless of mutational status of the cells.
      These effects translated into a pronounced delay of in vivo melanoma tumor growth
      which was, at least in part, dependent on intact immunity as evidenced by the
      restoration of tumor growth after CD4+ and CD8+ depletion. Given our findings, we
      provide the initial rationale for the further development of selective HDAC6
      inhibitors as potential therapeutic anti-melanoma agents. 

PMID- 25957815
TI  - Seroprevalence of chronic hepatitis B, as determined from dried blood spots,
      among children and their mothers in central Lao People's Democratic Republic: a
      multistage, stratified cluster sampling survey.
AB  - BACKGROUND: There is limited information regarding the prevalence of hepatitis B
      in Lao PDR, where the hepatitis disease burden is substantial. Thus, reliable
      seroprevalence data is needed for the disease, based on probability sampling.
      METHODS: A stratified, multistage, cluster sampling survey of hepatitis B surface
      antigen (HBsAg) positivity among children aged 5-9 years and their mothers aged
      15-45 years was conducted. Participants were selected randomly from the central
      region of Lao PDR via probability-proportional-to-size sampling. Blood samples
      were collected onto filter paper and subsequently analyzed using a
      chemiluminescent microparticle immunoassay. RESULTS: A total of 911 mother-and
      child pairs were collected; the seroprevalence of HBsAg was estimated to be 2.1%
      (95% confidence interval 0.8-3.4%) among children and 4.1% (95% confidence
      interval 2.6-5.5%) in their mothers after taking into account the sampling design
      and the weight of each sample. The children's HBsAg positivity was positively
      associated with maternal infection and being born in a non-health facility, while
      the maternal infection status was not associated with any background
      characteristic. CONCLUSIONS: Lao PDR has a relatively lower HBsAg prevalence in
      the general population compared to surrounding countries. To ensure comparability
      to other countries and to future data, rapid field tests are recommended for a
      nationwide prevalence survey.

PMID- 25957816
TI  - Optimizing diagnostic testing for Clostridium difficile: The perceptions of
      physicians and nurses on when to order testing for C difficile.
AB  - Physicians and nurses at a single hospital were surveyed on which risk factors
      were most important in deciding to order Clostridium difficile diagnostic
      testing. Disagreement between physicians and nurses on the relative importance of
      several of the risk factors warrants further investigation. 

PMID- 25957817
TI  - A multifaceted prevention program to reduce infection after cesarean section:
      Interventions assessed using an intensive postdischarge surveillance system.
AB  - BACKGROUND: We assessed the effects of the components of a multifaceted and
      evidence-based caesarean-section surgical site infection (SSI) prevention program
      on the SSI rate after cesarean section using a postdischarge surveillance (PDS)
      system. METHODS: Multiple prevention interventions were serially implemented. SSI
      case finding was undertaken through active inpatient surveillance and intensive
      PDS using a standardized form at the 6-week postdischarge visit. SSI diagnosis
      was made using the Centers for Disease Control and Prevention standardized
      criteria. All cesarean deliveries between July 2007 and December 2012 were
      included. Changes in SSI rate were analyzed using segmented regression analysis.
      RESULTS: Nine thousand four hundred forty-two cesarean sections were assessed
      during the study period. PDS forms were completed for 7,985 women (85%). SSI was
      detected in 451 cases (5.6%): 91% were superficial, 9% were deep/organ-space
      infections. The SSI rate decreased incrementally from 8.2% at baseline to 4.1%;
      significant decreases were observed after optimizing antibiotic prophylaxis
      timing, using a surgical safety checklist, and enhancing prenatal education to
      discourage prehospital self-removal of hair. Nonelective surgeries or those
      undertaken after >12 hours of rupture of membranes had a significantly higher
      rate compared with those without either risk factor (6.3% vs 3.2%; P < .001).
      CONCLUSIONS: A multifaceted SSI prevention strategy, with periodic feedback of
      data, led to a significant reduction in SSI rates after cesarean section.

PMID- 25957818
TI  - [New oral anticoagulants and prostate biopsy: Which usual precaution should we
      use?].
AB  - INTRODUCTION: In 2013, more than 30,000 prostate biopsies have been performed in
      France. Bleeding complications are not rare. It imposes meticulous perioperative
      management in order to avoid them. In a close future, new oral anticoagulants
      (NOAC) will probably substitute vitamin K antagonist in many indications. The
      management of these new drugs is not really familiar in urology. The authors have
      specified it by using a systematic literature search in association to guidelines
      analysis edited by learned society. METHODS: This article is based on a
      systematic literature search by using Pubmed database and by consulting
      international learned society of urology, anesthesiology or cardiology and the
      French National Agency of Drugs Security. RESULTS: There was no guidelines edited
      by urological learned society. A standardized protocol adapted to prostate
      biopsies has been suggested using French Anesthesiologist and Hemostasian
      guidelines. The authors recommended stopping the oral anticoagulant treatment 5
      days prior the biopsy. A bridge, by using a curative dose of heparin, was
      required during the preoperative period in order to manage the bleeding risk. It
      must be stopped 12 hours or 24 hours before biopsy (standard or low molecular
      weight heparin). Contrary to vitamin K antagonist, the re-initiation of the oral
      should begin 6-8 hours after procedure. The treatment should not overlap with
      heparin. The NOAC anticoagulant effect is quickly effective after 2 to 4 hours.
      The treatment should be re-initiated directly after the biopsy, in the absence of
      bleeding complications. CONCLUSIONS: The perioperative management of new oral
      anticoagulants seems to be more simple than vitamin K antagonist (VKA) during
      prostate biopsy. A standardized protocol should be recommended.

PMID- 25957819
TI  - Commentary on 'Trends in Major Lower Limb Amputations Related to Peripheral
      Arterial Disease in Hungary. A Nationwide Study (2004-2012)'.

PMID- 25957820
TI  - In the End, It All Comes Down to the Beginning!

PMID- 25957821
TI  - A novel method for diagnosis of smear-negative tuberculosis patients by combining
      a random unbiased Phi29 amplification with a specific real-time PCR.
AB  - In this study, we develop a novel method for diagnosis of smear-negative
      tuberculosis patients by performing a random unbiased Phi29 amplification prior
      to the use of a specific real-time PCR. The limit of detection (LOD) of the
      conventional real-time PCR was 100 colony-forming units (CFU) of MTB
      genome/reaction, while the REPLI real-time PCR assay could detect 0.4
      CFU/reaction. In comparison with the conventional real-time PCR, REPLI real-time
      PCR shows better sensitivity for the detection of smear-negative tuberculosis (P
      = 0.015). 

PMID- 25957823
TI  - Characterization of a collection of plasmid-containing bacteria isolated from an
      on-farm biopurification system used for pesticide removal.
AB  - Biopurification systems (BPS) are complex soil-related and artificially-generated
      environments usually designed for the removal of toxic compounds from
      contaminated wastewaters. The present study has been conducted to isolate and
      characterize a collection of cultivable plasmid-carrying bacterial isolates
      recovered from a BPS established for the decontamination of wastewater generated
      in a farmyard. Out of 1400 isolates, a collection of 75 plasmid-containing
      bacteria was obtained, of which 35 representative isolates comprising in total at
      least 50 plasmids were chosen for further characterization. Bacterial hosts were
      taxonomically assigned by 16S ribosomal RNA gene sequencing and phenotypically
      characterized according to their ability to grow in presence of different
      antibiotics and heavy metals. The study demonstrated that a high proportion of
      the isolates was tolerant to antibiotics and/or heavy metals, highlighting the on
      farm BPS enrichment in such genetic traits. Several plasmids conferring such
      resistances in the bacterial collection were detected to be either mobilizable or
      selftransmissible. Occurrence of broad host range plasmids of the incompatibility
      groups IncP, IncQ, IncN and IncW was examined with positive results only for the
      first group. Presence of the IS1071 insertion sequence, frequently associated
      with xenobiotics degradation genes, was detected in DNA obtained from 24 of these
      isolates, strongly suggesting the presence of yet-hidden catabolic activities in
      the collection of isolates. The results showed a remarkable diversity in the
      plasmid mobilome of cultivable bacteria in the BPS with the presence of abundant
      resistance markers of different types, thus providing a suitable environment to
      investigate the genetic structure of the mobile genetic pool in a model on-farm
      biofilter for wastewater decontamination in intensive agricultural production. 

PMID- 25957822
TI  - HPV16 antibodies as risk factors for oropharyngeal cancer and their association
      with tumor HPV and smoking status.
AB  - BACKGROUND: Antibodies (Abs) to the HPV16 proteome increase risk for HPV
      associated OPC (HPVOPC). The goal of this study was to investigate the
      association of a panel of HPV16 Abs with risk for OPC as well as the association
      of these Abs with tumor HPV and smoking status among patients with OPC. METHODS:
      IgG Abs to the HPV16 antigens E1, E2, E4, E5, E6, E7, L1, L2 were quantified
      using a programmable ELISA assay. Sera were obtained from 258 OPC patients at
      diagnosis and 250 healthy controls. HPV16 tumor status was measured by PCR for
      137 cases. Multivariable logistic regression was used to calculate odds ratios
      for the association of HPV16 Abs with risk for OPC. RESULTS: HPV16 E1, E2, E4,
      E5, E6, E7 and L1-specific IgG levels were elevated in OPC patients compared to
      healthy controls (p<0.05). After multivariable adjustment, Ab positivity for NE2,
      CE2, E6, and/or E7 was associated with OPC risk (OR [95% CI], 249.1 [99.3
      624.9]). Among patients with OPC, Ab positivity for these antigens was associated
      with tumor HPV status, especially among never or light smokers (OR [95% CI], 6.5
      [2.1-20.1] and OR [95% CI], 17.5 [4.0-77.2], respectively). CONCLUSIONS:
      Antibodies to HPV16 proteins are associated with increased risk for HPVOPC. Among
      patients with OPC, HPV16 Abs are associated with tumor HPV status, in particular
      among HPV positive patients with no or little smoking history.

PMID- 25957825
TI  - Federated queries of clinical data repositories: Scaling to a national network.
AB  - Federated networks of clinical research data repositories are rapidly growing in
      size from a handful of sites to true national networks with more than 100
      hospitals. This study creates a conceptual framework for predicting how various
      properties of these systems will scale as they continue to expand. Starting with
      actual data from Harvard's four-site Shared Health Research Information Network
      (SHRINE), the framework is used to imagine a future 4000 site network,
      representing the majority of hospitals in the United States. From this it becomes
      clear that several common assumptions of small networks fail to scale to a
      national level, such as all sites being online at all times or containing data
      from the same date range. On the other hand, a large network enables researchers
      to select subsets of sites that are most appropriate for particular research
      questions. Developers of federated clinical data networks should be aware of how
      the properties of these networks change at different scales and design their
      software accordingly. 

PMID- 25957824
TI  - Rural vs. non-rural differences and longitudinal bone changes by DXA and pQCT in
      men aged 20-66 years: A population-based study.
AB  - The purpose of this research was to determine whether there were differences in
      estimated means and rates of change in BMC, bone area, BMD and measures of bone
      geometry among men (n=544) from three distinct populations (Hutterite [rural],
      rural non-Hutterite, non-rural), and whether activity levels or calcium intake
      explain these population differences. Men were enrolled in the South Dakota Rural
      Bone Health Study and followed for 7.5 years to estimate means and rates of
      change in bone mass, density, size and geometry. Femoral neck (FN) and spine
      measurements were obtained every 18 months by DXA and distal radius (4% and 20%)
      measurements by pQCT. Activity measurements and calcium intake were obtained
      quarterly for the first 3 years and at 54, 72, and 90 months. Rural men had
      greater percent time in moderate plus vigorous activity (mean +/- SD: 22 +/- 10
      vs. 15 +/- 8%, p<0.001) and greater lean mass (69 +/- 9 vs. 66 +/- 10 kg, p=0.05)
      than non-rural men. Both rural populations (Hutterite and rural men) had larger
      femoral neck (FN) bone area and greater 20% radius cross-sectional area than non
      rural men ([least square means +/- SE] FN area: 5.90 +/- 0.02 and 5.86 +/- 0.02
      vs. 5.76 +/- 0.03 cm(2), p<0.001 and p=0.03 respectively and cross-sectional
      area: 171.0 +/-1.3 and 165.5 +/- 1.5 vs. 150.3 +/- 1.6mm(2), both p<0.001).
      Despite lower cortical vBMD in Hutterite and rural men compared to non-rural men
      (1182 +/- 2 and 1187 +/- 2 vs. 1192 +/- 2 mm(2), p<0.001 and p=0.06
      respectively), bone strength (pSSI) was greater (429 +/- 5 and 422 +/- 5 vs. 376
      +/- 6 mm(3), both p<0.001). The rates of change in femoral neck BMC and aBMD and
      trabecular vBMD also differed by rural lifestyle, with greater losses among non
      rural men in their 20s and 60s compared to both Hutterite and rural populations
      (time-by-age-by-group interactions, both p<0.01). Physical activity was not found
      to be a potential mediator of population differences. Baseline calcium intake was
      associated with FN aBMD (p=0.04), and increases in calcium intake were associated
      with spine BMC (p=0.04) and inversely associated with cortical area (p=0.02).
      There was some evidence for mediation by either baseline calcium intake or
      changes in calcium intake over the study period, but the influence on population
      differences were negligible. We speculate that rural-non-rural differences in
      bone occur earlier in life or are a result of factors that have not yet been
      identified.

PMID- 25957827
TI  - Seifert SM et al (Clin Infect Dis 2015; 60:804-10).

PMID- 25957826
TI  - Making pharmacogenomic-based prescribing alerts more effective: A scenario-based
      pilot study with physicians.
AB  - To facilitate personalized drug dosing (PDD), this pilot study explored the
      communication effectiveness and clinical impact of using a prototype clinical
      decision support (CDS) system embedded in an electronic health record (EHR) to
      deliver pharmacogenomic (PGx) information to physicians. We employed a conceptual
      framework and measurement model to access the impact of physician characteristics
      (previous experience, awareness, relative advantage, perceived usefulness),
      technology characteristics (methods of implementation-semi-active/active,
      actionability-low/high) and a task characteristic (drug prescribed) on
      communication effectiveness (usefulness, confidence in prescribing decision), and
      clinical impact (uptake, prescribing intent, change in drug dosing). Physicians
      performed prescribing tasks using five simulated clinical case scenarios,
      presented in random order within the prototype PGx-CDS system. Twenty-two
      physicians completed the study. The proportion of physicians that saw a relative
      advantage to using PGx-CDS was 83% at the start and 94% at the conclusion of our
      study. Physicians used semi-active alerts 74-88% of the time. There was no
      association between previous experience with, awareness of, and belief in a
      relative advantage of using PGx-CDS and improved uptake. The proportion of
      physicians reporting confidence in their prescribing decisions decreased
      significantly after using the prototype PGx-CDS system (p=0.02). Despite
      decreases in confidence, physicians perceived a relative advantage to using PGx
      CDS, viewed semi-active alerts on most occasions, and more frequently changed
      doses toward doses supported by published evidence. Specifically, sixty-five
      percent of physicians reduced their dosing, significantly for capecitabine
      (p=0.002) and mercaptopurine/thioguanine (p=0.03). These findings suggest a need
      to improve our prototype such that PGx CDS content is more useful and delivered
      in a way that improves physician's confidence in their prescribing decisions. The
      greatest increases in communication effectiveness and clinical impact of PGx-CDS
      are likely to be realized through continued focus on content, content delivery,
      and tailoring to physician characteristics. 

PMID- 25957828
TI  - Epidemiology and clinical profiles of Mycoplasma pneumoniae infection in
      hospitalized infants younger than one year.
AB  - BACKGROUND: Mycoplasma pneumoniae (M. pneumoniae) is an important pathogen of
      community-acquired pneumonia in children, but the epidemiology and clinical
      features of M. pneumoniae infection in infants are reported in only a few
      studies. This study aims to evaluate possible age-related differences in the
      presenting clinical features in infants with M. pneumoniae infection. METHODS: 24
      month longitudinal study on lower respiratory tract infection (LRTI) caused by M.
      pneumoniae, confirmed by both serology and polymerase chain reaction, was
      performed. Medical records of patients were reviewed for demographic, clinical
      and microbiological characteristics. RESULTS: Out of 2174 infants with LRTI
      admitted to the Children's Hospital Affiliated to Soochow University in Jiangsu
      Province, 80 were diagnosed with M. pneumoniae infection. We found that 15 were
      aged 1 to <5 months; 29 were aged 5 to <9 months; and 36 were aged 9 to <12
      months. M. pneumoniae infection mainly occurred in August to October. The
      presence of fever with a maximum temperature of >39.0  degrees C for >=3 days was
      more common in the 9 to <12 month age group (P < 0.05). Laboratory tests showed
      that the infants aged 9-12 months had a higher peripheral leukocyte (P = 0.035)
      and neutrophil (P = 0.015) count and a higher CRP level (P = 0.041). Moreover,
      the median length of hospitalization for infants aged 1 to <5 months was shorter
      than that in the other two groups. CONCLUSION: Our work provides important
      clinical information about infants with M. pneumoniae infection and highlights
      that younger infants with M. pneumoniae infection may have a milder clinical
      course than older infants.

PMID- 25957829
TI  - Ipilimumab-induced hypophysitis: review of the literature.
AB  - PURPOSE: Ipilimumab is a human monoclonal antibody against cytotoxic T-lymphocyte
      antigen 4 available as an immunotherapy mainly for advanced melanoma. It induces
      an activation of T cells, resulting in an immune-mediated anti-tumor response and
      also immune-related adverse events, including hypophysitis. The aim of this
      review is to identify and discuss features concerning ipilimumab-induced
      hypophysitis (IIH). DESIGN: A MEDLINE research of all years of publication of IIH
      was conducted. We gathered information regarding clinical, radiologic and
      laboratory features of 71 cases recorded in the literature. RESULTS: In our
      review, IIH was more frequent among older and male patients. Fatigue and headache
      were the most frequent initial clinical manifestations of IIH and enlargement of
      the pituitary gland at MRI was present in the majority of patients. Those who
      received more than 3 cycles of ipilimumab had more fatigue (p = 0.04) and
      arthritis (p = 0.04). Adrenal insufficiency was more prevalent in men (p =
      0.007). Glucocorticoid therapy and hormone replacement were required in most
      patients and pituitary function recovery was uncommon. Low prolactin at diagnosis
      tended to predict permanent pituitary dysfunction (p = 0.07). CONCLUSION:
      Hypopituitarism as a consequence of IIH, if not promptly recognized, can lead to
      potentially fatal events, such as adrenal insufficiency. IIH can be easily
      managed with glucocorticoids and hormonal replacement; therefore, physicians
      should be familiar with the key aspects of this condition. More studies to
      develop screening protocols and therapeutic intervention algorithms should be
      performed to decrease morbidity related to IIH.

PMID- 25957830
TI  - Fluorescent sensing of pyrophosphate anion in synovial fluid based on DNA
      attached magnetic nanoparticles.
AB  - In this work, a new fluorescent method for sensitive detection of pyrophosphate
      anion (P2O7(4-), PPi) in the synovial fluid was developed using fluorophore
      labeled single-stranded DNA-attached Fe3O4 NPs. The sensing approach is based on
      the strong affinity of PPi to Fe3O4 NPs and highly efficient fluorescent
      quenching ability of Fe3O4 NPs for fluorophore labeled single-stranded DNA. In
      the presence of PPi, the fluorescence would enhance dramatically due to
      desorption of fluorophore labeled single-stranded DNA from the surface of Fe3O4
      NPs, which allowed the analysis of PPi in a very simple manner. The proposed
      sensing system allows for the sensitive determination of PPi in the range of 2.0
      * 10(-7)-4 * 10(-6)M with a detection limit of 76 nM. Importantly, the protocol
      exhibits excellent selectivity for the determination of PPi over other phosphate
      containing compounds. The method was successfully applied to the determination of
      PPi in the synovial fluid, which suggests our proposed method has great potential
      for diagnostic purposes.

PMID- 25957831
TI  - Graphene-CNT nanohybrid aptasensor for label free detection of cardiac biomarker
      myoglobin.
AB  - We report a label free electrochemical detection of cardiac bio-marker myoglobin
      (Mb) on aptamer functionalized rGO/CNT nanostructured electrodes by measuring its
      direct electron transfer (DET). Configured as a highly responsive aptasensor, the
      newly developed biosensing platform exhibits synergistic effect of the nano
      hybrid functional construct by combining good electrical properties and the
      facile chemical functionality of nanohybrid for the compatible bio-interface
      development. The specific anti-Mb aptamer was generated by five iterative SELEX
      (Systematic evolution of ligands by exponential enrichment) rounds, showing high
      senstivity (KD ~65 pM). The aptamer functionalized rGO/CNT nanostructured
      electrodes demonstrated a significant increase in signal response with a
      detection limit of ~0.34 ng/mL in the dynamic response range between 1 ng/mL and
      4 ug/mL for Mb. The newly developed DET assay format presents a promising
      candidate in point-of-care diagnosis for routine screening of Mb in patient's
      samples.

PMID- 25957832
TI  - Intense Raman scattering on hybrid Au/Ag nanoplatforms for the distinction of MMP
      9-digested collagen type-I fiber detection.
AB  - Well-ordered Au-nanorod arrays were fabricated using the focused ion beam method
      (denoted as fibAu_NR). Au or Ag nanoclusters (NCs) of various sizes and
      dimensions were then deposited on the fibAu_NR arrays using electron beam
      deposition to improve the surface-enhanced Raman scattering (SERS) effect, which
      was verified using a low concentration of crystal violet (10(-)(5)M) as the probe
      molecule. An enhancement factor of 6.92 * 10(8) was obtained for NCsfibAu_NR,
      which is attributed to the combination of intra-NC and NR localized surface
      plasmon resonance. When 4-aminobenzenethiol (4-ABT)-coated Au or Ag nanoparticles
      (NPs) were attached to NCsfibAu_NR, the small gaps between 4-ABT-coated NPs and
      intra-NCs allowed detection at the single-molecule level. Hotspots formed at the
      interfaces of NCs/NRs and NPs/NCs at a high density, producing a strong local
      electromagnetic effect. Raman spectra from as-prepared type I collagen (Col-I)
      and Ag-NP-coated Col-I fibers on NCsfibAu_NR were compared to determine the
      quantity of amino acids in their triple helix structure. Various concentrations
      of matrix-metalloproteinase-9-digested Col-I fibers on NCsfibAu_NR were
      qualitatively examined at a Raman laser wavelength of 785nm to determine the
      changes of amino acids in the Col-I fiber structure. The results can be used to
      monitor the growth of healing Col-I fibers in a micro-environment.

PMID- 25957833
TI  - Simultaneous detection of multiple bioactive pollutants using a multiparametric
      biochip for water quality monitoring.
AB  - Water is a renewable resource but yet finite. Its sustainable usage and the
      maintenance of a good quality are essential for an intact environment, human life
      and a stable economy. Emerging technologies aim for a continuous monitoring of
      water quality, overcoming periodic analytical sampling, and providing information
      on the current state of inshore waters in real time. So does the here presented
      cell-based sensor system which uses RLC-18 cells (rat liver cells) as the
      detection layer for the detection of water pollutants. The electrical read-out of
      the system, cellular metabolism, oxygen consumption and morphological integrity
      detects small changes in the water quality and indicates a possible physiological
      damage caused. A generalized functional linear model was implemented in order to
      regress the chemicals present in the sample on the electrical read-out. The
      chosen environmental pollutants to test the system were chlorpyrifos, an
      organophosphate pesticide, and tetrabromobisphenol A, a flame retardant. Each
      chemical gives a very characteristic response, but the toxicity is mitigated if
      both chemicals are present at once. This will focus our attention on the
      statistical approach which is able to discriminate between these pollutants. 

PMID- 25957834
TI  - A peptide-based fluorescent chemosensor for multianalyte detection.
AB  - A novel multifunctional peptide fluorescent chemosensor (DP-3) with a lysine
      backbone and double sides conjugated with histidine and dansyl groups has been
      designed and synthesized by solid phase synthesis. This chemosensor is a
      promising analytical tool for detecting Zn(2+), Cu(2+), and S(2-) based on
      different mechanisms in 100% aqueous solutions, and intracellular biosensing has
      been successfully actualized. The peptide beacon structure of DP-3 makes it more
      stable and capable of achieving multianalyte detection, especially for sulfide
      ions. Until now, there have been few examples of using a peptide fluorescent
      chemosensor to detect anions with a continuous method. As designed, DP-3 exhibits
      excellent cell permeation and low biotoxicity and displays high selectivity and
      sensitivity, with Zn(2+) and Cu(2+) detection limits of 82 nM and 78 nM,
      respectively. This study raises the new possibility of a highly selective peptide
      fluorescent chemosensor for multifunctional detection, including cation and
      anions, by different mechanisms in environmental and biological systems. We
      expect that this work will inspire the development of a multifunctional beacon
      peptide-based fluorescent chemosensor library using modifiable lateral and
      terminal groups for a variety of practical applications in physiological and
      pathological events.

PMID- 25957835
TI  - Site-directed mutagenesis of tobacco anionic peroxidase: Effect of additional
      aromatic amino acids on stability and activity.
AB  - Tobacco anionic peroxidase (TOP) is known to effectively catalyze luminol
      oxidation without enhancers, in contrast to horseradish peroxidase (HRP). To
      pursue structure-activity relationship studies for TOP, two amino acids have been
      chosen for mutation, namely Thr151, close to the heme plane, and Phe140 at the
      entrance to the active site pocket. Three mutant forms TOP F140Y, T151W and
      F140Y/T151W have been expressed in Escherichia coli, and reactivated to yield
      active enzymes. Single-point mutations introducing additional aromatic amino acid
      residues at the surface of TOP exhibit a significant effect on the enzyme
      catalytic activity and stability as judged by the results of steady-state and
      transient kinetics studies. TOP T151W is up to 4-fold more active towards a
      number of aromatic substrates including luminol, whereas TOP F140Y is 2-fold more
      stable against thermal inactivation and 8-fold more stable in the reaction
      course. These steady-state observations have been rationalized with the help of
      transient kinetic studies on the enzyme reaction with hydrogen peroxide in a
      single turnover regime. The stopped-flow data reveal (a) an increased stability
      of F140Y Compound I towards hydrogen peroxide, and thus, a higher operational
      stability as compared to the wild-type enzyme, and (b) a lesser leakage of
      oxidative equivalents from TOP T151W Compound I resulting in the increased
      catalytic activity. The results obtained show that TOP unique properties can be
      further improved for practical applications by site-directed mutagenesis.

PMID- 25957836
TI  - The epinephrine increases tyrosine hydroxylase expression through upregulating
      thioredoxin-1 in PC12 cells.
AB  - Epinephrine is a stress hormone which is sharply increased in response to acute
      stress and is continuously elevated during persistent stress. Thioredoxin-1 (Trx
      1) is a redox regulating protein and is induced under various stresses. Our
      previous study has shown that epinephrine induces the expression of Trx-1.
      Tyrosine hydroxylase (TH) is the major rate-limiting enzyme in catecholamine
      biosynthesis in response to stress. However, how TH is regulated by epinephrine
      is still unknown. In the present study, we found that epinephrine increased the
      expression of TH in a dose- and time-dependent manner in PC12 cells, which was
      inhibited by propranolol (beta-adrenergic receptor inhibitor), but not by
      phenoxybenzamine (alpha-adrenergic receptor inhibitor). The increase of TH was
      also inhibited by SQ22536 (adenylyl cyclase inhibitor), H-89(PKA inhibitor) and
      LY294002 (phosphatidylinositol 3 kinase inhibitor). More importantly,
      overexpression of Trx-1 significantly enhanced the expression of TH, while Trx-1
      siRNA suppressed TH expression induced by epinephrine. These results suggest that
      Trx-1 is involved in TH expression induced by epinephrine in PC12 cells. 

PMID- 25957837
TI  - Fine particulate matter and the risk of autism spectrum disorder.
AB  - The causes of autism spectrum disorder (ASD) are not well known. Recent
      investigations have suggested that air pollution, including PM2.5, may play a
      role in the onset of this condition. The objective of the present work was to
      investigate the association between prenatal and early childhood exposure to fine
      particulate matter (PM2.5) and risk for childhood ASD. A population-based case
      control study was conducted in children born between January 1, 2005 and December
      31, 2009 in six counties in Southwestern Pennsylvania. ASD cases were recruited
      from specialty autism clinics, local pediatric practices, and school-based
      special needs services. ASD cases were children who scored 15 or above on the
      Social Communication Questionnaire (SCQ) and had written documentation of an ASD
      diagnosis. Controls were children without ASD recruited from a random sample of
      births from the Pennsylvania state birth registry and frequency matched to cases
      on birth year, gender, and race. A total of 217 cases and 226 controls were
      interviewed. A land use regression (LUR) model was used to create person- and
      time-specific PM2.5 estimates for individual (pre-pregnancy, trimesters one
      through three, pregnancy, years one and two of life) and cumulative (starting
      from pre-pregnancy) key developmental time periods. Logistic regression was used
      to investigate the association between estimated exposure to PM2.5 during key
      developmental time periods and risk of ASD, adjusting for mother's age,
      education, race, and smoking. Adjusted odds ratios (AOR) were elevated for
      specific pregnancy and postnatal intervals (pre-pregnancy, pregnancy, and year
      one), and postnatal year two was significant, (AOR=1.45, 95% CI=1.01-2.08). We
      also examined the effect of cumulative pregnancy periods; noting that starting
      with pre-pregnancy through pregnancy, the adjusted odds ratios are in the 1.46
      1.51 range and significant for pre-pregnancy through year 2 (OR=1.51, 95% CI=1.01
      2.26). Our data indicate that both prenatal and postnatal exposures to PM2.5 are
      associated with increased risk of ASD. Future research should include multiple
      pollutant models and the elucidation of the biological mechanism for PM2.5 and
      ASD. 

PMID- 25957839
TI  - Porous titanium manufactured by a novel powder tapping method using spherical
      salt bead space holders: Characterisation and mechanical properties.
AB  - Porous Ti with open porosity in the range of 70-80% has been made using Ti powder
      and a particulate leaching technique using porous, spherical, NaCl beads. By
      incorporating the Ti powder into a pre-existing network of salt beads, by tapping
      followed by compaction, salt dissolution and "sintering", porous structures with
      uniform density, pore and strut sizes and a predictable level of connectivity
      have been produced, showing a significant improvement on the structures made by
      conventional powder mixing processes. Parts made using beads with sizes in the
      range of 0.5-1.0 mm show excellent promise as porous metals for medical devices,
      showing structures and porosities similar to those of commercial porous metals
      used in this sector, with inter-pore connections that are similar to trabecular
      bone. The elastic modulus (0.86 GPa) is lower than those for commercial porous
      metals and more closely matches that of trabecular bone and good compressive
      yield strength is retained (21 MPa). The ability to further tailor the structure,
      in terms of the density and the size of the pores and interconnections has also
      been demonstrated by immersion of the porous components in acid.

PMID- 25957838
TI  - Reliability of perfluoroalkyl substances in plasma of 100 women in two
      consecutive pregnancies.
AB  - The potential toxicity of background exposure to perfluoroalkyl substances
      (PFASs) is currently under active investigation. Such investigations typically
      rely on a single measure of PFAS concentration, yet the longer-term reliability
      of a single measure has not been well characterized, especially among
      reproductive-aged women. Our aim was to investigate the association between PFAS
      plasma concentrations of 100 women in two consecutive pregnancies and explore
      changes in plasma concentration related to reproductive factors. The women in our
      study were enrolled in the Norwegian Mother and Child Cohort Study (MoBa) from
      2003 to 2009. About half of them breastfed exclusively for 6 months and the rest
      of the participants did not breastfeed between the two consecutive pregnancies
      (median time between pregnancies: 18 months). Maternal blood was collected at mid
      pregnancy and plasma was analyzed for 10 PFASs. Statistical analyses were
      restricted to 6 PFASs that were quantifiable in more than 80% of the samples. We
      estimated the correlation between repeated PFAS measurements, the percentage
      change between pregnancies and the effect of several reproductive factors in
      multivariate linear regression models of PFAS concentrations in the second
      pregnancy. The Pearson correlation coefficient between repeated PFAS measurements
      was, for perfluorooctane sulfonate (PFOS), 0.80; perfluorooctanoate (PFOA), 0.50;
      perfluorohexane sulfonate (PFHxS), 0.74; perfluorononanoate (PFNA), 0.39;
      perfluoroundecanoate (PFUnDA), 0.71; and perfluorodecanoate (PFDA), 0.60.
      Adjustment for maternal age, delivery year, and time and breastfeeding between
      pregnancies did not substantially affect the observed correlations. We found 44
      47% median reductions in the concentrations of PFOS, PFOA and PFHxS between
      pregnancies, while the change in concentrations between pregnancies was smaller
      and more variable for PFNA, PFUnDA and PFDA. The variation in plasma
      concentrations in the second pregnancy was mainly accounted for by the
      concentration in the first pregnancy; for PFOS, PFOA, and PFNA, breastfeeding
      also accounted for a substantial proportion. In conclusion, we found the
      reliability of PFAS measurements in maternal plasma to be moderate to high, and
      in these data, several factors, especially breastfeeding, were related to plasma
      concentrations. 

PMID- 25957840
TI  - The aqueous humor outflow pathways in glaucoma: A unifying concept of disease
      mechanisms and causative treatment.
AB  - Intraocular pressure (IOP) is the critical risk factor for glaucoma, a
      neurodegenerative disease and frequent cause of blindness worldwide. As of today,
      all effective strategies to treat glaucoma aim at lowering IOP. IOP is generated
      and maintained via the aqueous humor circulation system in the anterior eye.
      Aqueous humor is secreted by the ciliary processes and exits the eye through the
      trabecular meshwork (TM) or the uveoscleral outflow pathways. The TM outflow
      pathways provide resistance to aqueous humor outflow and IOP builds up in
      response to it. In the normal eye, the resistance is localized in the inner wall
      region, which comprises the juxtacanalicular connective tissue (JCT) and the
      inner wall endothelium of Schlemm's canal (SC). Outflow resistance in the inner
      wall region is lowered through the contraction of the ciliary muscle or the
      relaxation of contractile myofibroblasts in the posterior part of the TM and the
      adjacent scleral spur. Patients with primary open-angle glaucoma (POAG), the most
      frequent form of glaucoma, typically suffer from an abnormally high outflow
      resistance of the inner wall region. There is increasing evidence that the
      increase in TM outflow resistance in POAG is the result of a characteristic
      change in the biological properties of the resident cells in the JCT, which
      increasingly acquire the phenotype of contractile myofibroblasts. This scenario
      strengthens simultaneously both their actin cytoskeleton and their directly
      associated extracellular matrix fibrils, leads to overall stiffening of the
      tissue, and is modulated by transforming growth factor-beta (TGF-beta)/connective
      tissue growth factor (CTGF) signaling. Essentially comparable changes appear to
      occur in SC endothelial cells in glaucoma. Causative therapy concepts targeting
      the aqueous outflow pathways in glaucoma should aim at interfering with this
      process either by attenuating TM or SC stiffness, and/or by modulating TGF
      beta/CTGF signaling. 

PMID- 25957841
TI  - Historical Perspectives on the Behavioral Function of the Insula.

PMID- 25957843
TI  - Report on KOSMOS Summer University at the School of Analytical Sciences Adlershof
      (Berlin): limits and scales in analytical sciences.

PMID- 25957842
TI  - Determination of agmatine using isotope dilution UPLC-tandem mass spectrometry:
      application to the characterization of the arginine decarboxylase pathway in
      Pseudomonas aeruginosa.
AB  - A method has been developed for the direct determination of agmatine in bacterial
      culture supernatants using isotope dilution ultra performance liquid
      chromatography (UPLC)-tandem mass spectrometry (UPLC-MS/MS). Agmatine
      determination in bacterial supernatants is comprised of spiking culture or
      isolate supernatants with a fixed concentration of uniformly labeled
      (13)C5,(15)N4-agmatine (synthesized by decarboxylation of uniformly labeled
      (13)C6,(15)N4-arginine using arginine decarboxylase from Pseudomonas aeruginosa)
      as an internal standard, followed by derivatization with 4-fluoro-7-nitro-2,1,3
      benzoxadiazole (NBDF) to improve the reversed-phase chromatographic retention
      characteristics of agmatine, as well as the selectivity and sensitivity of UPLC
      MS/MS detection of this amine in complex biologically derived mixtures.
      Intrasample precisions for measurement of agmatine in culture supernatants
      average 4.1% (relative standard deviation). Calibration curves are linear over
      the range 5 nM to 10 MUM, and the detection limit is estimated at 1.5 nM. To
      demonstrate the utility of the method, agmatine levels in supernatants of
      overnight cultures of wild-type (UCBPP-PA14), as well as arginine decarboxylase
      and agmatine deiminase mutant strains of P. aeruginosa strain UCBPP-PA14 were
      measured. This method verified that the mutant strains are lacking the specific
      metabolic capabilities to produce and metabolize agmatine. In addition,
      measurement of agmatine in supernatants of a panel of clinical isolates from
      patients with cystic fibrosis revealed that three of the P. aeruginosa isolates
      hyper-secreted agmatine into the supernatant, hypothesized to be a result of a
      mutation in the aguA gene. Because agmatine has potential inflammatory activities
      in the lung, this phenotype may be a virulence factor for P. aeruginosa in the
      lung environment of cystic fibrosis patients.

PMID- 25957844
TI  - Bio-layer interferometry of a multivalent sulfated virus nanoparticle with
      heparin-like anticoagulant activity.
AB  - Heparin is a sulfated glycosaminoglycan that is routinely used as an
      anticoagulant. It is typically purified from bovine or porcine sources, leading
      to heterogeneity that poses several challenges when used clinically. We have
      found that the bacteriophage Qbeta can be selectively sulfated to yield virus
      like nanoparticles (sulf-VLP) that elicit anticoagulant activity similar to
      heparin. In an effort to explore the binding interactions that heparin-like VLPs
      make with cationic targets, described herein are bio-layer interferometry studies
      utilizing the BLItz platform that evaluate the interaction of sulf-VLP with the
      cationic peptide CDK5 (50% Lys). Streptavidin biosensors modified with biotin
      CDK5 were found to bind strongly to sulf-VLP and not to the underivatized
      nanoparticle. Titration of sulf-VLP yielded concentration-dependent sensorgrams,
      permitting calculation of rate and equilibrium constants: k(on) = (8 +/- 3) *
      10(6) s(-1) for the association phase, k(off )= (5 +/- 2) * 10(-3) M s(-1) for
      the dissociation phase, yielding an overall dissociation constant K(D)~ 1 nM.
      Fitting was best achieved using an equation possessing both exponential and
      linear terms, suggesting a mechanism more complex than 1:1 binding. To mitigate
      multivalency and rebinding effects, experiments were conducted with protamine
      (~70% Arg) added during the dissociation phase, leading to more pronounced
      dissociation curves and k off values that yielded a near-linear relationship with
      protamine concentration.

PMID- 25957845
TI  - Decreased level of phosphatidylcholine (16:0/20:4) in multiple myeloma cells
      compared to plasma cells: a single-cell MALDI-IMS approach.
AB  - Lipid metabolic changes under diseased conditions, particularly in solid tumors,
      are attracting increased attention. However, in non-solid tumors, including most
      hematopoietic tumors, lipid analyses are scarce. Multiple myeloma (MM) is a
      plasma cell disorder arising from bone marrow, and the lipid status of MM cells
      has not been reported yet. In this study, we analyzed flow cytometry-sorted
      single MM cells and normal plasma cells (NPCs) using matrix-assisted laser
      desorption/ionization-imaging mass spectrometry (MALDI-IMS), a two-dimensional
      label-free mass spectrometry technique for biomolecular analysis, to obtain
      specific lipid information. We isolated 1.31-5.77% of MM cells and 0.03-0.24% of
      NPCs using fluorescence-activated cell sorting (FACS). Analysis of purified cells
      using MALDI-IMS at the single-cell level revealed that the peak intensity and ion
      signals of phosphatidylcholine [PC (16:0/20:4) + H](+) at m/z 782.5 were
      significantly decreased in MM cells compared to NPCs. By examining particular
      cell populations rather than cell mixtures, our method can become a suitable tool
      for the analysis of rare cell populations at the single-cell level and advance
      the understanding of MM progression.

PMID- 25957846
TI  - Assessing the role of chemical components in cellular responses to atmospheric
      particle matter (PM) through chemical fractionation of PM extracts.
AB  - In order to further our understanding of the influence of chemical components and
      ultimately specific sources of atmospheric particulate matter (PM) on pro
      inflammatory and other adverse cellular responses, we promulgate and apply a
      suite of chemical fractionation tools to aqueous aerosol extracts of PM samples
      for analysis in toxicity assays. We illustrate the approach with a study that
      used water extracts of quasi-ultrafine PM (PM0.25) collected in the Los Angeles
      Basin. Filtered PM extracts were fractionated using Chelex, a weak anion
      exchanger diethylaminoethyl (DEAE), a strong anion exchanger (SAX), and a
      hydrophobic C18 resin, as well as by desferrioxamine (DFO) complexation that
      binds iron. The fractionated extracts were then analyzed using high-resolution
      sector field inductively coupled plasma mass spectrometry (SF-ICPMS) to determine
      elemental composition. Cellular responses to the fractionated extracts were
      probed in an in vitro rat alveolar macrophages model with measurement of reactive
      oxygen species (ROS) production and the cytokine tumor necrosis factor-alpha (TNF
      alpha). The DFO treatment that chelates iron was very effective at reducing the
      cellular ROS activity but had only a small impact on the TNF-alpha production. In
      contrast, the hydrophobic C18 resin treatment had a small impact on the cellular
      ROS activity but significantly reduced the TNF-alpha production. The use of
      statistical methods to integrate the results across all treatments led to the
      conclusion that sufficient iron must be present to participate in the chemistry
      needed for ROS activity, but the amount of ROS activity is not proportional to
      the iron solution concentration. ROS activity was found to be most related to
      cationic mono- and divalent metals (i.e., Mn and Ni) and oxyanions (i.e., Mo and
      V). Although the TNF-alpha production was not significantly affected by the
      chelexation of iron, it was greatly impacted by the removal of organics with the
      C18 resin and all other metal removal methods, suggesting that iron is not a
      critical pathway leading to TNF-alpha production, but a wide range of soluble
      metals and organic compounds in particulate matter play a role. Although the
      results are specific to the Los Angeles Basin, where the samples used in the
      study were collected, the method employed in the study can be widely employed to
      study the role of components of particulate matter in in vitro or in vivo assays.

PMID- 25957847
TI  - Biomimetic biosensor to distinguish between inhibitory and non-inhibitory factor
      VIII antibodies.
AB  - Patients with hereditary or acquired haemophilia A may develop inhibitory factor
      VIII (FVIII) antibodies. These disrupt FVIII activity predominantly by preventing
      the formation of the tenase complex, leading to a serious bleeding disorder.
      Antibodies without inhibiting activity, however, can also be found when screening
      patients with haemophilia A under FVIII supplementation. Therefore, the detection
      of only these allo- or autoantibodies from plasma is not sufficient. Rather, the
      characterization of the antibody-induced effects on the coagulation cascade
      should be considered due to its great diagnostic importance. Currently,
      inhibitory activities are detected by the functional Bethesda assay, which
      directly measures the delay in clotting time by the patient plasma. However, this
      assay does not provide information on the cause of the inhibition. Here, we
      report the development of a surface plasmon resonance (SPR) biosensor that has
      the potential to integrate both quantitative and functional information on
      patient antibody characteristics in one measurement. Recombinant FVIII protein
      was immobilized on the sensor surface to detect antibodies from patient plasma.
      The interaction of the FIX- and FXa-clotting proteins with the formed anti
      FVIII/FVIII complex could be detected subsequently within the same SPR
      measurement cycle. Inhibitory antibodies led to the prevention of these
      interactions. Thus, discrimination between the clinically relevant inhibitory and
      non-inhibitory antibodies was enabled. In a group of 16 patients with inhibitory
      antibodies (both ELISA- and Bethesda-positive), 5 patients with non-inhibitory
      antibodies (ELISA-positive but Bethesda-negative) and 12 healthy controls,
      diagnostic sensitivity and specificity data of 100% for the FIX interaction were
      achieved using this biomimetic biosensor approach. The new method allows for
      detection and quantification, as well as for evaluation of inhibitory activity of
      allo- and autoantibodies, using small sample volume and short analysis time.

PMID- 25957848
TI  - Synthesis of magnetic biocomposite for efficient adsorption of azo dye from
      aqueous solution.
AB  - A novel magnetic biocomposite was synthesized using metal chlorides and aquatic
      macrophytes by co-precipitation method. The resulting product, magnetic
      biocomposite was characterized by Fourier transform infrared spectra (FTIR), X
      ray diffraction (XRD), Energy-dispersive X-ray spectroscopy (EDX) and Scanning
      electron microscope (SEM). The adsorption performance of the magnetic
      biocomposite was tested with removal of Metanil Yellow dye from aqueous solution.
      The effect of influencing parameters such as initial dye concentration, solution
      pH and agitation were investigated. The equilibrium isotherm was well described
      by the Langmuir model with the with maximum adsorption capacity of 90.91mg/g.
      Adsorption kinetics experiments were carried out and the data were well fitted by
      a pseudo-second-order equation. The results revealed that the magnetic
      biocomposite could efficiently adsorb the azo dyes from aqueous solution, and the
      spent adsorbents could be recovered completely by magnetic separation process.
      Therefore, the prepared magnetic biocomposite could thus be used as promising
      adsorbent for the removal of azo dyes from polluted water. 

PMID- 25957849
TI  - Emerging biorefinery technologies for Indian forest industry to reduce GHG
      emissions.
AB  - The production of biofuels as alternative energy source over fossil fuels has
      gained immense interest over the years as it can contribute significantly to
      reduce the greenhouse gas (GHG) emissions from energy production and utilization.
      Also with rapidly increasing fuel price and fall in oil wells, the present
      scenario forces us to look for an alternative source of energy that will help us
      in the operation of industrial as well as the transportation sector. The pulp
      mills in India are one of the many options. The pulp mills in India can help us
      to produce bio-fuels by thermo-chemical/biochemical conversion of black liquor
      and wood residues. These technologies include extraction of hemi-cellulose from
      wooden chips and black liquor, lignin from black liquor, methanol from evaporator
      condensates, biogas production from waste sludge, syngas production from biomass
      using gasification and bio-oil production from biomass using pyrolysis. The
      objective of this paper is to overview these emerging bio-refinery technologies
      that can be implemented in Indian Forest Industry to get bio-fuels, bio-chemicals
      and bio-energy to reduce GHG emissions. 

PMID- 25957850
TI  - Radiotherapy and PGEMOX/GELOX regimen improved prognosis in elderly patients with
      early-stage extranodal NK/T-cell lymphoma.
AB  - The optimal treatment strategy for elderly patients with natural killer/T-cell
      lymphoma (NKTCL) remains to be established. A total of 63 elderly patients with
      newly diagnosed NKTCL were retrospectively reviewed. Among the patients with
      stage I-II disease, 58.3 % received radiotherapy (RT) +/- chemotherapy, and 41.7
      % received chemotherapy alone. Compared with chemotherapy alone, RT +/-
      chemotherapy elicited a significantly higher overall response rate (ORR) (100 vs.
      57.1 %, P < 0.001) and substantially prolonged 5-year overall survival (OS) (55.3
      vs. 18.0 %, P < 0.001) in patients with stage I-II disease. Compared with other
      chemotherapeutic regimens, pegaspargase plus gemcitabine and oxaliplatin
      (PGEMOX)/L-asparaginase plus gemcitabine and oxaliplatin (GELOX) was associated
      with a significantly higher ORR (92.9 vs. 51.6 %, P = 0.009) and a significantly
      improved 5-year OS (78.6 vs. 23.9 %, P = 0.010) in patients with stage I-II
      disease. Nine patients with stage I-II disease who were treated with PGEMOX/GELOX
      followed by RT had an encouraging outcome (5-year OS 100 %, 5-year progression
      free survival (PFS) 85.7 %), which was superior to that of patients receiving
      other regimens followed by RT. In conclusion, RT played an important role for
      elderly patients with early-stage NKTCL, and the PGEMOX/GELOX regimen was
      superior to other regimens. The combination of them may be a promising treatment
      option. 

PMID- 25957851
TI  - Prostate-specific membrane antigen-radioguided surgery for metastatic lymph nodes
      in prostate cancer.
AB  - With the advent of (68)Ga-labeled prostate-specific membrane antigen-N,N'-bis[2
      hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid ((68)Ga-PSMA
      HBED-CC) positron emission tomography (PET) hybrid imaging in prostate cancer
      (PCa), even small metastatic lymph nodes (LNs) can be visualized. However,
      intraoperative detection of such LNs may not be easy owing to their inconspicuous
      morphology and/or atypical localization. The aim of our feasibility study was to
      evaluate PSMA-radioguided surgery for detection of metastatic LNs. One patient
      with primary PCa and evidence of LN metastases and four PCa patients with
      evidence of recurrent disease to regional LNs on (68)Ga-PSMA-HBED-CC PET hybrid
      imaging received an intravenous injection of an (111)In-PSMA investigation and
      therapy agent 24h before surgery. Metastatic LNs were tracked intraoperatively
      using a gamma probe with acoustic and visual feedback. All radioactive-positive
      LN specimens detected in vivo were confirmed by ex vivo measurements and
      corresponded to PSMA-avid metastatic disease according to histopathology
      analysis. Intraoperative use of the gamma probe detected all PSMA-positive
      lesions identified on preoperative (68)Ga-PSMA-HBED-CC PET. Detection of small
      subcentimeter metastatic LNs was facilitated, and PSMA-radioguided surgery in two
      patients revealed additional lesions close to known tumor deposits that were not
      detected by preoperative (68)Ga-PSMA-HBED-CC PET. However, greater patient
      numbers and long-term follow-up data are needed to determine the future role of
      PSMA-radioguided surgery. 

PMID- 25957852
TI  - Student perceptions of a healthy university.
AB  - As complex environments within which individuals and populations operate,
      universities present important contexts for understanding and addressing health
      issues. The healthy university is an example of the settings approach, which
      adopts a whole system perspective, aiming to make places within which people,
      learn, live, work and play supportive to health and well-being. The UK Healthy
      Universities Network has formulated an online toolkit, which includes a Self
      Review Tool, intended to enable universities to assess what actions they need to
      take to develop as a healthy university. This paper presents findings from
      consultative research undertaken with students from universities in England,
      Scotland and Wales, which explored what they believe, represents a healthy
      university. METHODS: Student surveys and focus groups were used to collect data
      across eleven universities in England, Scotland and Wales. A priori themes were
      used to develop our own model for a healthy university, and for the thematic
      coding phase of analysis. FINDINGS: A healthy university would promote student
      health and well-being in every aspect of its business from its facilities and
      environment through to its curriculum. Access to reasonably priced healthy food
      and exercise facilities were key features of a healthy university for students in
      this study. The Self-Review Tool has provided a crucial start for universities
      undertaking the journey towards becoming a healthy university. In looking to the
      future both universities and the UK Healthy Universities Network will now need to
      look at what students want from their whole university experience, and consider
      how the Self-Review Tool can help universities embrace a more explicit conceptual
      framework. CONCLUSION: The concept of a healthy university that can tailor its
      facilities and supportive environments to the needs of its students will go some
      way to developing students who are active global citizens and who are more likely
      to value and prioritise health and well-being, in the short and long term through
      to their adult lives.

PMID- 25957853
TI  - Reliability and relative validity of three physical activity questionnaires in
      Taizhou population of China: the Taizhou Longitudinal Study.
AB  - OBJECTIVE: To examine the test-retest reliabilities and relative validities of
      the Chinese version of short International Physical Activity Questionnaire (IPAQ
      S-C), the Global Physical Activity Questionnaire (GPAQ-C), and the Total Energy
      Expenditure Questionnaire (TEEQ-C) in a population-based prospective study, the
      Taizhou Longitudinal Study (TZLS). STUDY DESIGN: A longitudinal comparative
      study. METHODS: A total of 205 participants (male: 38.54%) aged 30-70 years
      completed three questionnaires twice (day one and day nine) and physical activity
      log (PA-log) over seven consecutive days. The test-retest reliabilities were
      evaluated using intra-class correlation coefficients (ICCs) and the relative
      validities were estimated by comparing the data from physical activity
      questionnaires (PAQs) and PA-log. RESULTS: Good reliabilities were observed
      between the repeated PAQs. The ICCs ranged from 0.51 to 0.80 for IPAQ-C, 0.67 to
      0.85 for GPAQ-C, and 0.74 to 0.94 for TEEQ-C, respectively. Energy expenditure of
      most PA domains estimated by the three PAQs correlated moderately with the
      results recorded by PA-log except the walking domain of IPAQ-S-C. The partial
      correlation coefficients between the PAQs and PA-log ranged from 0.44 to 0.58 for
      IPAQ-S-C, 0.26 to 0.52 for GPAQ-C, and 0.41 to 0.72 for TEEQ-C, respectively.
      Bland-Altman plots showed acceptable agreement between the three PAQs and PA-log.
      CONCLUSION: The three PAQs, especially TEEQ-C, were relatively reliable and valid
      for assessment of physical activity and could be used in TZLS.

PMID- 25957854
TI  - Cardiac autonomic function during sleep: effects of alcohol dependence and
      evidence of partial recovery with abstinence.
AB  - Chronic alcoholism is associated with the development of cardiac and peripheral
      autonomic nervous system (ANS) pathology. The aim of the present study was to
      evaluate the extent to which recovery in ANS function could be demonstrated over
      the first 4 months of abstinence. Fifteen alcoholics (7 women) were studied on
      three occasions: within a month of detoxification, at approximately 2 months post
      detox, and at 4 months post-detox. Thirteen control subjects (6 women) were also
      studied on three occasions with inter-study intervals matching those of the
      alcoholics. Six alcoholics relapsed, 48.7 +/- 27.9 days following the initial PSG
      session. ANS function was assessed in the first part of stable non-rapid eye
      movement sleep. Frequency-domain power spectral analysis of heart rate
      variability (HRV) produced variables including: heart rate (HR), total power (TP;
      an index representing total HR variability), High Frequency power (HFa; an index
      reflecting cardiac vagal modulation), HF proportion of total power (HFprop
      sympathovagal balance), and HF peak frequency (HFpf; an index reflecting
      respiration rate). Overall, high total and high frequency variability and low
      sympathovagal balance and myocardial contractility are considered as desired
      conditions to promote cardiovascular health. At initial assessment, alcoholics
      had a higher HR (p < 0.001) and respiratory rate (p < 0.01), and lower vagal
      activity (HFa; p < 0.01) than controls. Alcoholics showed evidence of recovery in
      HR (p = 0.039) and HFa (p = 0.031) with 4 months of abstinence. Alcoholics with
      higher TP at the initial visit showed a greater improvement in TP from the
      initial to the 4 month follow-up session (r = 0.75, p < 0.05). Alcoholics showed
      substantial recovery in HR and vagal modulation of HRV with 4 months of
      abstinence, with evidence that the extent of recovery in HRV may be partially
      determined by the extent of alcohol dependence-related insult to the cardiac ANS
      system. These data support other studies showing recovery in a number of ANS,
      central nervous system, and behavioral domains with abstinence, even in those
      with long-term dependence.

PMID- 25957856
TI  - The Psychological Context of Sexual Compulsivity Among Men Who Have Sex with Men.
AB  - Among men who have sex with men (MSM), sexual compulsivity is associated with
      overlapping psychosocial and behavioral health problems. Because difficulties
      with emotion regulation are thought to be one important feature, this study
      examined whether affective states and traumatic stress symptoms were
      independently associated with key dimensions of sexual compulsivity. Data were
      collected in San Francisco for the Urban Men's Health Study-2002 from May 24,
      2002 to January 19, 2003. In total, 711 MSM recruited via probability-based
      sampling completed a mail-in questionnaire that assessed psychological factors
      and substance use. Dissociation related to traumatic stress and any stimulant use
      in the past 6 months were independently associated with more frequent sexual
      thoughts or urges. Increased anger and HIV-positive serostatus were independently
      associated with a greater perception that sexual behavior is difficult to
      control. Clinical research is needed to examine if interventions targeting
      emotion regulation and traumatic stress can boost the effectiveness of HIV
      prevention efforts among MSM who experience difficulties related to managing
      sexual behaviors.

PMID- 25957855
TI  - Assessment and treatment of insomnia in adult patients with alcohol use
      disorders.
AB  - Insomnia in patients with alcohol dependence has increasingly become a target of
      treatment due to its prevalence, persistence, and associations with relapse and
      suicidal thoughts, as well as randomized controlled studies demonstrating
      efficacy with behavior therapies and non-addictive medications. This article
      focuses on assessing and treating insomnia that persists despite 4 or more weeks
      of sobriety in alcohol-dependent adults. Selecting among the various options for
      treatment follows a comprehensive assessment of insomnia and its multifactorial
      causes. In addition to chronic, heavy alcohol consumption and its effects on
      sleep regulatory systems, contributing factors include premorbid insomnia; co
      occurring medical, psychiatric, and other sleep disorders; use of other
      substances and medications; stress; environmental factors; and inadequate sleep
      hygiene. The assessment makes use of history, rating scales, and sleep diaries as
      well as physical, mental status, and laboratory examinations to rule out these
      factors. Polysomnography is indicated when another sleep disorder is suspected,
      such as sleep apnea or periodic limb movement disorder, or when insomnia is
      resistant to treatment. Sobriety remains a necessary, first-line treatment for
      insomnia, and most patients will have some improvement. If insomnia-specific
      treatment is needed, then brief behavioral therapies are the treatment of choice,
      because they have shown long-lasting benefit without worsening of drinking
      outcomes. Medications work faster, but they generally work only as long as they
      are taken. Melatonin agonists; sedating antidepressants, anticonvulsants, and
      antipsychotics; and benzodiazepine receptor agonists each have their benefits and
      risks, which must be weighed and monitored to optimize outcomes. Some relapse
      prevention medications may also have sleep-promoting activity. Although it is
      assumed that treatment for insomnia will help prevent relapse, this has not been
      firmly established. Therefore, insomnia and alcohol dependence might be best
      thought of as co-occurring disorders, each of which requires its own treatment.

PMID- 25957857
TI  - Social Cognition Variables and Victimization as Predictors of Sexual Debut Among
      Adolescents in South Africa and Tanzania: A Multi-group SEM Analysis.
AB  - Early sexual debut is common in South Africa and Tanzania, with potentially
      negative reproductive health outcomes. The role of violence as a predictor of
      sexual debut was studied, in a context of predictors borrowed from social
      cognition models. Data were taken from cluster-randomized trials of school-based
      HIV prevention interventions in three sites in South Africa and Tanzania.
      Analyses consisted of descriptive statistics and multi-group structural equation
      modelling. The basic model functioned fairly well for Cape Town, but less well
      for Mankweng and Dar es Salaam (low R(2) values). Attitudes were the strongest
      predictor of intention. Adding socio-demographic variables to the model did not
      reduce the associations much and neither did subsequent inclusion of violence.
      Sexual debut was strongly associated with victimization; adding violence also
      substantially increased R(2) for sexual debut. Besides social cognition factors,
      intimate partner violence should be addressed in future research on reproductive
      health interventions for adolescents. 

PMID- 25957858
TI  - Inter-joint coordination strategies during unilateral stance following first
      time, acute lateral ankle sprain: A brief report.
AB  - BACKGROUND: This investigation combined measures of inter-joint coordination and
      stabilometry to evaluate eyes-open (condition 1) and eyes-closed (condition 2)
      static unilateral stance performance in a group of participants with an acute,
      first-time lateral ankle sprain injury in comparison to a control group. METHODS:
      Sixty-six participants with an acute first-time lateral ankle sprain and 19 non
      injured controls completed three 20-second unilateral stance task trials in
      conditions 1 and 2. An adjusted coefficient of multiple determination statistic
      was used to compare stance limb 3-D kinematic data for similarity in the aim of
      establishing patterns of inter-joint coordination for these groups. FINDINGS:
      Between-group analyses revealed significant differences in stance limb inter
      joint coordination strategies for conditions 1 and 2. Injured participants
      displayed increases in ankle-hip linked coordination compared to controls in
      condition 1 (sagittal/frontal plane: 0.12 [0.09] vs 0.06 [0.04]; eta(2)=.16) and
      condition 2 (sagittal/frontal plane: 0.18 [0.13] vs 0.08 [0.06]; eta(2)=0.37).
      INTERPRETATION: Participants with acute first-time lateral ankle sprain exhibit a
      hip-dominant coordination strategy for static unilateral stance compared to non
      injured controls.

PMID- 25957859
TI  - Giant cell arteritis: diagnosis and treatment.
AB  - Giant cell arteritis is the most common primary systemic vasculitis in adults.
      The condition is granulomatous arteritis of large and medium vessels, which
      occurs almost exclusively in patients aged 50 years or more. This article reviews
      the diagnosis and treatment of the disease. 

PMID- 25957860
TI  - Epstein-Barr virus-positive primary cutaneous follicle centre lymphoma; an age
      related phenomenon?
AB  - Primary cutaneous follicle centre lymphoma is the most frequently encountered
      primary cutaneous B cell lymphoma, often presenting in the head and neck region.
      Treatment is locally directed with surgery and/or radiotherapy. The prognosis is
      usually excellent with only local recurrences and generally no dissemination to
      extracutaneous sites. Epstein-Barr virus (EBV) is frequently encountered in
      lymphoproliferative disorders associated with immunosuppression, typically
      iatrogenic and congenital, or acquired as a consequence of a human
      immunodeficiency virus infection. More recently, age-related immune senescence
      has been proposed as a main driver in the evolution of EBV-positive
      lymphoproliferative disorders. We report a 50-year-old male presenting with a 2-3
      year history of an inflamed eruption centred on the forehead and scalp.
      Incisional biopsy showed pathological features typical of primary cutaneous
      follicle centre lymphoma (PCFCL), and in the absence of systemic disease, he was
      treated with local radical radiotherapy. A cutaneous relapse occurred 10 months
      after initial diagnosis and 29 months after completing radiotherapy, he presented
      with a right-sided submandibular lymph node mass. Pathological examination of an
      excised node showed an EBV-positive diffuse large B cell lymphoma. Retrospective
      examination of the presenting PCFCL also showed the neoplastic lymphoid cells to
      be positive for EBV, both by in situ hybridization and on immunohistochemical
      staining for LMP1. EBV-associated PCFCL is an extremely rare occurrence. We
      speculate that, in this case, the EBV-positive lymphoma has most likely arisen as
      a consequence of age-related immune senescence, thereby further expanding the
      pathological spectrum of age-related EBV-associated B cell lymphoproliferations. 

PMID- 25957862
TI  - Olfactory impairment in older adults is associated with poorer diet quality over
      5 years.
AB  - PURPOSE: Decreased smell could cause appetite suppression and malnutrition.
      However, there is a paucity of longitudinal data between olfaction and
      nutritional status in older adults. We aimed to prospectively examine the
      relationship between olfactory impairment and overall diet quality (reflecting
      adherence to dietary guidelines) in a population-based cohort of older adults.
      METHODS: We used 5-year follow-up data from 557 adults (aged 60+ years at
      baseline) whose olfaction was measured using the San Diego Odor Identification
      Test (SDOIT). Dietary data were collected using a validated semiquantitative food
      frequency questionnaire. A total diet score (TDS) was calculated for intake of
      selected food groups and nutrients for each participant as described in the
      national dietary guidelines. Final scores ranged from 0 to 20; higher scores
      indicated closer adherence to dietary guidelines. RESULTS: After adjusting for
      all potential confounders, older adults with moderate/severe olfactory impairment
      (SDOIT score <= 3; lower scores indicate impairment) compared with those with no
      olfactory impairment had significantly lower adjusted mean (+/-SE) TDS, 9.09
      (0.40) versus 9.94 (0.10), p = 0.04. Women with moderate/severe impaired
      olfaction (i.e., scored poorly on the odor identification test) compared with
      those with normal olfaction had significantly lower adjusted mean TDS, 8.87
      (0.69) versus 10.31 (0.13), p = 0.04. No associations were observed between
      olfaction and TDS in men. CONCLUSIONS: Olfactory impairment in older women could
      signal an increased risk of poorer diet quality, defined as adherence to national
      dietary guidelines. Additional longitudinal studies are needed to confirm or
      refute the observed link between olfactory loss and overall patterns of food
      intake in older adults.

PMID- 25957861
TI  - Epidemiology, Diagnosis, and Management of Esophageal Adenocarcinoma.
AB  - Esophageal adenocarcinoma (EAC) is rapidly increasing in incidence in Western
      cultures. Barrett's esophagus is the presumed precursor lesion for this cancer.
      Several other risk factors for this cancer have been described, including chronic
      heartburn, tobacco use, white race, and obesity. Despite these known
      associations, most patients with EAC present with symptoms of dysphagia from late
      stage tumors; only a small number of patients are identified by screening and
      surveillance programs. Diagnostic analysis of EAC usually commences with upper
      endoscopy followed by cross-sectional imaging. Endoscopic ultrasonography is
      useful to assess the local extent of disease as well as the involvement of
      regional lymph nodes. T1a EAC may be treated endoscopically, and some patients
      with T1b disease may also benefit from endoscopic therapy. Locally advanced
      disease is generally managed with esophagectomy, often accompanied by neoadjuvant
      chemoradiotherapy or chemotherapy. The prognosis is based on tumor stage;
      patients with T1a tumors have an excellent prognosis, whereas few patients with
      advanced disease have long-term survival. 

PMID- 25957864
TI  - Factors that increase diagnostic yield of surgical lung biopsy in pediatric
      oncology patients.
AB  - PURPOSE: Recent data demonstrate that surgical lung biopsy in immunocompromised
      children, including oncology patients, alters therapy in only 50% of cases. We
      hypothesized that there are factors identifiable preoperatively which can predict
      the patients who will or will not benefit from surgical biopsy. METHODS: We
      reviewed the medical records of all children with malignancy who underwent
      surgical lung biopsy between 2004 and 2013 at a single institution, excluding
      those children who had previously undergone a solid organ or bone marrow
      transplant. RESULTS: Eighty lung wedge biopsies were performed (median age 13
      years, IQR 5.25-16; 63% male, n=50) 53 (66%) of which led to a change in patient
      management. The majority of biopsies were performed to diagnose a new mass or
      differentiate infection from metastases (mass group) (n=68, 85%), and 12 biopsies
      (15%) were performed to diagnose a known infection for antibiotic guidance
      (infection group). Children in the infection group were more likely to be febrile
      preoperatively, were more likely to be an inpatient preoperatively, and had a
      lower absolute neutrophil count at the time of biopsy. Patients in the infection
      group had higher postoperative mortality rates and higher rates of major
      complications. CONCLUSION: In pediatric oncology patients, surgical lung biopsy
      has a lower diagnostic yield and higher complication rate when performed for
      antibiotic guidance. Prior to proceeding with biopsy in this high-risk patient
      population, surgeons and oncologists should carefully weigh the potential risks
      and benefits.

PMID- 25957865
TI  - Predicting temporal shifts in the spring occurrence of overwintered Scotinophara
      lurida (Hemiptera: Pentatomidae) and rice phenology in Korea with climate change.
AB  - Climate change could shift the phenology of insects and plants and alter their
      linkage in space and time. We examined the synchrony of rice and its insect pest,
      Scotinophara lurida (Burmeister), under the representative concentration pathways
      (RCP) 8.5 climate change scenario by comparing the mean spring immigration time
      of overwintered S. lurida with the mean rice transplanting times in Korea. The
      immigration time of S. lurida was estimated using an overwintered adult flight
      model. The rice transplanting time of three cultivars (early, medium, and medium
      late maturing) was estimated by forecasting the optimal cultivation period using
      leaf appearance and final leaf number models. A temperature increase
      significantly advanced the 99% immigration time of S. lurida from Julian day
      192.1 in the 2000s to 178.4 in the 2050s and 163.1 in the 2090s. In contrast,
      rice transplanting time was significantly delayed in the early-maturing cultivar
      from day 141.2 in the 2000s to 166.7 in the 2050s and 190.6 in the 2090s, in the
      medium-maturing cultivar from day 130.6 in the 2000s to 156.6 in the 2050s and
      184.7 in the 2090s, and in the medium-late maturing cultivar from day 128.5 in
      2000s to 152.9 in the 2050s and 182.3 in the 2090s. These simulation results
      predict a significant future phenological asynchrony between S. lurida and rice
      in Korea.

PMID- 25957863
TI  - A novel canine kidney cell line model for the evaluation of neoplastic
      development: karyotype evolution associated with spontaneous immortalization and
      tumorigenicity.
AB  - The molecular mechanisms underlying spontaneous neoplastic transformation in
      cultured mammalian cells remain poorly understood, confounding recognition of
      parallels with the biology of naturally occurring cancer. The broad use of
      tumorigenic canine cell lines as research tools, coupled with the accumulation of
      cytogenomic data from naturally occurring canine cancers, makes the domestic dog
      an ideal system in which to investigate these relationships. We developed a
      canine kidney cell line, CKB1-3T7, which allows prospective examination of the
      onset of spontaneous immortalization and tumorigenicity. We documented the
      accumulation of cytogenomic aberrations in CKB1-3T7 over 24 months in continuous
      culture. The majority of aberrations emerged in parallel with key phenotypic
      changes in cell morphology, growth kinetics, and tumor incidence and latency.
      Focal deletion of CDKN2A/B emerged first, preceding the onset and progression of
      tumorigenic potential, and progressed to a homozygous deletion across the cell
      population during extended culture. Interestingly, CKB1-3T7 demonstrated a
      tumorigenic phenotype in vivo prior to exhibiting loss of contact inhibition in
      vitro. We also performed the first genome-wide characterization of the canine
      tumorigenic cell line MDCK, which also exhibited CDKN2A/B deletion. MDCK and CKB1
      3T7 cells shared several additional aberrations that we have reported previously
      as being highly recurrent in spontaneous canine cancers, many of which, as with
      CDKN2A/B deletion, are evolutionarily conserved in their human counterparts. The
      conservation of these molecular events across multiple species, in vitro and in
      vivo, despite their contrasting karyotypic architecture, is a powerful indicator
      of a common mechanism underlying emerging neoplastic activity. Through integrated
      cytogenomic and phenotypic characterization of serial passages of CKB1-3T7 from
      initiation to development of a tumorigenic phenotype, we present a robust and
      readily accessible model (to be made available through the American Type Culture
      Collection) of spontaneous neoplastic transformation that overcomes many of the
      limitations of earlier studies.

PMID- 25957867
TI  - The application of thrombin generation in real life clinical situations.

PMID- 25957866
TI  - Association between red blood cell distribution width (RDW) and carotid artery
      atherosclerosis (CAS) in patients with primary ischemic stroke.
AB  - BACKGROUND: The present study aimed to explore the association between RDW and
      CAS in patients with ischemic stroke, expecting to find a new and significant
      diagnosis index for clinical practice. METHODS: This cross-sectional study
      involves 432 consecutive patients with primary ischemic stroke (within 72 h). All
      subjects were confirmed by magnetic resonance imaging, and underwent physical
      examination, laboratory tests and carotid ultrasonography check. Finally, 392
      patients were included according to the exclusion criteria. The odds ratios of
      independent variables were calculated using stepwise multiple logistic
      regression. RESULTS: Carotid intimal-medial thickness (IMT) and RDW are both
      significantly different between CAS group and control group. Univariate analyses
      show that high-sensitive C-reactive protein (Hs-CRP) and RDW (r=0.436) are both
      in significantly positive association with IMT. Stepwise multiple logistic
      regression shows that RDW is an independent protective factor of CAS in patients
      with ischemic stroke. Compared with the lowest quartile, the second to fourth
      quartiles are 1.13 (95% CI: 1.13-3.05), 2.02 (95% CI: 1.66-4.67), and 3.10 (95%
      CI: 2.46-7.65), respectively. CONCLUSION: The present study suggested that RDW
      level were higher than non-CAS in patients with primary ischemic stroke. Our
      results facilitated a bridge to connect RDW with ischemic stroke and further
      confirmed the role of RDW in the progression of the ischemic stroke.

PMID- 25957868
TI  - Effect of n-alkanes on lipid bilayers depending on headgroups.
AB  - Phase behavior and structural properties were examined for phospholipid bilayers
      having different headgroups (DMPC, DMPS and DMPE) with added n-alkanes to study
      effect of flexible additives. Change in the temperatures of main transition of
      the lipid/alkane mixtures against the length of added alkanes depends largely on
      the headgroup. Theoretical analysis of the change of the temperature of
      transition indicates that the headgroup dependence is dominantly originated in
      the strong dependence of total enthalpy on the headgroups. The results of X-ray
      diffraction show that the enthalpic stabilization due to enhanced packing of acyl
      chains of the lipid by alkanes in the gel phase causes the headgroup-dependent
      change in the phase transition behavior. The enhanced packing in the gel phase
      also leads to easy emergence of the subgel phase with very short relaxation time
      at room temperature in the DMPE-based bilayers. 

PMID- 25957869
TI  - Baseline study of morphometric traits of wild Capsicum annuum growing near two
      biosphere reserves in the Peninsula of Baja California for future conservation
      management.
AB  - BACKGROUND: Despite the ecological and socioeconomic importance of wild Capsicum
      annuum L., few investigations have been carried out to study basic
      characteristics. The peninsula of Baja California has a unique characteristic
      that it provides a high degree of isolation for the development of unique highly
      diverse endemic populations. The objective of this study was to evaluate for the
      first time the growth type, associated vegetation, morphometric traits in plants,
      in fruits and mineral content of roots, stems and leaves of three wild
      populations of Capsicum in Baja California, Mexico, near biosphere reserves.
      RESULTS: The results showed that the majority of plants of wild Capsicum annuum
      have a shrub growth type and were associated with communities consisting of 43
      species of 20 families the most representative being Fabaceae, Cactaceae and
      Euphorbiaceae. Significant differences between populations were found in plant
      height, main stem diameter, beginning of canopy, leaf area, leaf average and
      maximum width, stems and roots dry weights. Coverage, leaf length and dry weight
      did not show differences. Potassium, sodium and zinc showed significant
      differences between populations in their roots, stems and leaves, while magnesium
      and manganese showed significant differences only in roots and stems, iron in
      stems and leaves, calcium in roots and leaves and phosphorus did not show
      differences. Average fruit weight, length, 100 fruits dry weight, 100 fruits pulp
      dry weight and pulp/seeds ratio showed significant differences between
      populations, while fruit number, average fruit fresh weight, peduncle length,
      fruit width, seeds per fruit and seed dry weight, did not show differences.
      CONCLUSIONS: We concluded that this study of traits of wild Capsicum, provides
      useful information of morphometric variation between wild populations that will
      be of value for future decision processes involved in the management and
      preservation of germplasm and genetic resources.

PMID- 25957870
TI  - Outcomes in the offspring of mothers with pre-diabetes during pregnancy: a
      protocol for a systematic review.
AB  - BACKGROUND: Despite the increasing prevalence of pre-diabetes worldwide, there is
      insufficient literature on the impact of gestational pre-diabetes on offspring
      outcomes. The objective of this systematic review is to determine the risk of
      developing adverse outcomes for the offspring in women with pre-diabetes compared
      to women with normal glucose levels and women with gestational diabetes mellitus.
      METHODS/DESIGN: A systematic search of the published literature will be conducted
      for experimental and observational studies that report outcomes in the offspring
      of mothers with pre-diabetes during pregnancy. Databases including EMBASE,
      PsycINFO, and PubMed will be searched from 1979 (the year when the terms impaired
      glucose tolerance and pre-diabetes were coined) to December 2014. Screening of
      identified articles and data extraction will be conducted in duplicate and
      independently. Methodological quality of the included studies will be assessed
      using the Newcastle-Ottawa scale. Discrepancies will be resolved by consensus or
      by consulting a third author. Meta-analyses will be performed, and findings will
      be reported according to the preferred reporting items for systematic reviews and
      meta-analyses (PRISMA) and the meta-analysis of observational studies in
      epidemiology (MOOSE) guidelines. DISCUSSION: Determining the effect of pre
      diabetes on offspring outcome will be important for clinicians providing care to
      pregnant women and their offspring. This review will also identify any gaps in
      the current literature on this topic and provide direction for future research in
      this area of study. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015015536.

PMID- 25957872
TI  - Late Reactivation of Cherubism in a Patient With New-Onset Polycystic Ovary
      Syndrome.
AB  - PURPOSE: The aim of the present study was to describe a case of cherubism with
      late progression, after skeletal maturity had been reached, that coincided with a
      recent diagnosis of polycystic ovary syndrome (PCOS). PATIENTS AND METHODS: We
      reviewed the published data and searched for any reported association between
      cherubism and PCOS. We also reviewed the cases of late reactivation of cherubism.
      RESULTS: This is, to our knowledge, the first case report of cherubism associated
      with PCOS. CONCLUSION: Cherubism is a rare condition, which, in its normal
      course, becomes quiescent after puberty. Only a few cases of late growth have
      been reported. The understanding of the condition has evolved in recent years,
      with a better appreciation of the underlying genetics and pathogenesis of the
      disease. However, much remains unknown about this rare entity. We describe a case
      of cherubism reactivation that coincided with changes related to PCOS. Both PCOS
      and cherubism are associated with a low-grade inflammatory state.

PMID- 25957871
TI  - Knowledge-based radiation therapy (KBRT) treatment planning versus planning by
      experts: validation of a KBRT algorithm for prostate cancer treatment planning.
AB  - BACKGROUND: A knowledge-based radiation therapy (KBRT) treatment planning
      algorithm was recently developed. The purpose of this work is to investigate how
      plans that are generated with the objective KBRT approach compare to those that
      rely on the judgment of the experienced planner. METHODS: Thirty volumetric
      modulated arc therapy plans were randomly selected from a database of prostate
      plans that were generated by experienced planners (expert plans). The anatomical
      data (CT scan and delineation of organs) of these patients and the KBRT algorithm
      were given to a novice with no prior treatment planning experience. The
      inexperienced planner used the knowledge-based algorithm to predict the dose that
      the OARs receive based on their proximity to the treated volume. The population
      based OAR constraints were changed to the predicted doses. A KBRT plan was
      subsequently generated. The KBRT and expert plans were compared for the achieved
      target coverage and OAR sparing. The target coverages were compared using the
      Uniformity Index (UI), while 5 dose-volume points (D10, D30, D50, D70 and D90)
      were used to compare the OARs (bladder and rectum) doses. Wilcoxon matched-pairs
      signed rank test was used to check for significant differences (p<0.05) between
      both datasets. RESULTS: The KBRT and expert plans achieved mean UI values of 1.10
      +/- 0.03 and 1.10 +/- 0.04, respectively. The Wilcoxon test showed no
      statistically significant difference between both results. The D90, D70, D50, D30
      and D10 values of the two planning strategies, and the Wilcoxon test results
      suggests that the KBRT plans achieved a statistically significant lower bladder
      dose (at D30), while the expert plans achieved a statistically significant lower
      rectal dose (at D10 and D30). CONCLUSIONS: The results of this study show that
      the KBRT treatment planning approach is a promising method to objectively
      incorporate patient anatomical variations in radiotherapy treatment planning.

PMID- 25957873
TI  - Automatic Superimposition of Palatal Fiducial Markers for Accurate Integration of
      Digital Dental Model and Cone Beam Computed Tomography.
AB  - PURPOSE: Obtaining a detailed dentition image is important for 3-dimensional
      orthognathic surgical simulation. The purpose of the present study was to
      evaluate the accuracy of a method using automatic superimposition of intraoral
      fiducial markers for integrating the digital dental model with the cone beam
      computed tomography (CBCT) scan. PATIENTS AND METHODS: A preliminary test was
      performed on a plastic skull model for the proper selection of the size and
      number of the fiducial markers fixed to the palatal plate. Five patients were
      enrolled in the present study. Plaster dental models were taken and scanned.
      Integration of the upper dental and occlusion dental image with the CBCT scan was
      performed by superimposition of the markers. The occlusion dental image was used
      to connect the lower dental image and the corresponding position of the CBCT
      mandibular dentition. The root mean square difference (RMSD) was used to evaluate
      the accuracy of fiducial marker superimposition, and the Euclidean distances were
      measured between 2 occlusion surfaces to evaluate the registration accuracy.
      RESULTS: The RMSD was less than 0.13 mm in the superimposition of fiducial
      markers, and the Euclidean distance was less than 0.28 mm in the occlusal surface
      deviation. The results showed high accuracy on integration. The patients reported
      good tolerance to the markers. CONCLUSION: This superimposition method provided
      high accuracy for the replacement of dentition using CBCT and was patient- and
      user-friendly for clinical application.

PMID- 25957874
TI  - Oral Rehabilitation of Adult Edentulous Siblings Severely Lacking Alveolar Bone
      Due to Ectodermal Dysplasia: A Report of 2 Clinical Cases and a Literature
      Review.
AB  - The oral conditions of adult edentulous patients with ectodermal dysplasia (ED)
      often lead to decreased physical and psychological health, and the negative
      effects can become as extreme as social and psychological isolation. However,
      restoring oral function of adult edentulous patients with ED using zygomatic
      implants (ZIs) or conventional implants (CIs) remains challenging for dentists
      because of the severe atrophy of these patients' alveolar ridges. This report
      describes 2 cases of adult edentulous siblings with ED; they exhibited severe
      alveolar bone atrophy and were treated with ZIs and CIs as bases to augment the
      bone in their anterior jaws. For these patients, bone augmentation was completed
      with an autogenous fibular graft. Although there was mild evidence of bone graft
      resorption in the maxilla, the bone augmentation procedures were successful in
      the 2 patients. Effective osseointegration of the implants was obtained. After
      placement, the functional and esthetic results of the oral rehabilitation were
      acceptable. More importantly, restoration of the patients' oral function enhanced
      their self-confidence and self-esteem. Therefore, restoring oral function in
      adult patients with ED and edentulous jaws using ZIs and CIs as the bases for
      bone augmentation is an effective approach. 

PMID- 25957875
TI  - Incorporating Simulation Into Oral and Maxillofacial Surgery Residency Education
      and Training: Christiana Care's Method.

PMID- 25957876
TI  - Differences Among Deviations, Genders, and Observers in the Perception of Eye and
      Nose Asymmetry.
AB  - PURPOSE: This study investigated the degree and range of recognition of canting
      of the interpupillary line and deviation of the nose, which were regarded as
      "normal," "acceptable," and "needing surgical correction," according to different
      observer groups. MATERIALS AND METHODS: Four different groups (40 each for
      laypeople, dental students, general dentists, and orthodontists) rated 11
      simulated asymmetric images with canted eyes and a deviated nose separately. The
      raters categorized each image as normal, socially "acceptable" and not requiring
      correction, or abnormal and would benefit from correction. Survival analysis was
      used to evaluate the scope of perception. RESULTS: The degree of recognition for
      eye-canting and nose deviation was 2.31 and 2.92, respectively. Eye-canting and
      nose deviation had lower degrees of recognition in the clockwise direction (2.13
      degrees ) and on the left side (2.65 degrees ), respectively. Women showed a
      lower degree of the "upper limit of the acceptable range" for canted eyes, and
      men showed a lower "degree of recognition" and "upper limit of the acceptable
      range" for a deviated nose. Orthodontists showed a larger upper limit of the
      acceptable range for eye-canting (P < .001). CONCLUSIONS: The perceptions of
      asymmetry of canted eyes and deviated nose were affected by gender, direction of
      asymmetry, and observer groups.

PMID- 25957877
TI  - Dislocation of Mandibular Condyle Into Middle Cranial Fossa: Two Alternative
      Methods for Two Patients.
AB  - Dislocation of the mandibular condyle into the middle cranial fossa is rare, and
      the number of cases discussed in published studies is limited. Various treatment
      routes have been suggested, and the entire published data are based on the
      presentations of single cases. The present report presents 2 cases of dislocation
      of the mandibular condyle into the middle cranial fossa. The first case was
      treated with closed reduction in the early stage; however, the second case, which
      was treated in the late stage, required open reduction. Both the methods of
      reduction and the key aspects of diagnosis are discussed. 

PMID- 25957878
TI  - Faculty Time in Dental School-Based OMS Department.

PMID- 25957879
TI  - Angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism is not a
      risk factor for hypertension in SLE nephritis.
AB  - SLE is a systemic autoimmune disease with high prevalence of hypertension. Around
      40-75 % of SLE patients develop nephritis, a major cause of hypertension and
      mortality. Angiotensin-converting enzyme (ACE) maintains the blood pressure and
      blood volume homeostasis. An insertion/deletion (I/D) polymorphism in intron 16
      of ACE gene was reported to influence the development of hypertension, nephritis,
      and cardiovascular diseases in different ethnic populations. Despite compelling
      evidence for the high prevalence of hypertension in individuals with SLE,
      underlying factors for its development are not well studied. With this
      background, we analyzed the influence of ACE insertion/deletion polymorphism on
      susceptibility to SLE, development of nephritis and hypertension, other clinical
      features and autoantibody phenotype in South Indian SLE patients. Three hundred
      patients with SLE and 460 age and sex similar ethnicity matched individuals were
      included as patients and healthy controls, respectively. The ACE gene
      insertion/deletion polymorphism was analyzed by PCR. Insertion (I) and deletion
      (D) alleles were observed to be equally distributed among patients (57 and 43 %)
      and controls (59 and 41 %), respectively. The mutant (D) allele did not confer
      significant risk for SLE (II vs. ID: p = 0.4, OR 1.15, 95 % CI 0.8-1.6; II vs.
      DD: p = 0.34, OR 1.22, 95 % CI 0.8-1.85). There was no association of the ACE
      genotype or the allele with development of lupus nephritis (II vs. ID: p = 0.19,
      OR 1.41, 95 % CI 0.84-2.36; II vs. DD: p = 0.41, OR 0.74, 95 % CI 0.38-1.41) or
      hypertension (II vs. ID: p = 0.85, OR 0.9, 95 % CI 0.43-1.8; II vs. DD: p = 0.66,
      OR 1.217, 95 % CI 0.5-2.8). The presence of mutant allele (D) was not found to
      influence any clinical features or autoantibody phenotype. The insertion/deletion
      polymorphism of the ACE gene is not a genetic risk factor for SLE and does not
      influence development of hypertension or lupus nephritis in South Indian Tamils.

PMID- 25957880
TI  - Axial spondyloarthritis: the heart of the matter.
AB  - A variety of cardiovascular clinical manifestations have been described in
      patients with spondyloarthritis, especially in well-established ankylosing
      spondylitis. These include both structural heart disease, conduction defects and
      ischemic heart disease. The true prevalence of cardiovascular involvement in
      patients with axial spondyloarthritis, including non-radiographic disease needs
      to be further defined. 

PMID- 25957882
TI  - Solid-state NMR studies of Ziegler-Natta and metallocene catalysts.
AB  - Ziegler-Natta catalysts are the workhorses of polyolefin production. However,
      although they have been used and intensively studied for half a century, there is
      still no comprehensive picture of their mechanistic operation. New techniques are
      needed to gain more insight in these catalysts. Solid-state NMR has reached a
      high level of sophistication over the last few decades and holds great promise
      for providing a deeper insight in Ziegler-Natta catalysis. This review outlines
      the possibilities for solid-state NMR to characterize the different components
      and interactions in Ziegler-Natta and metallocene catalysts. An overview is given
      of some of the expected mechanisms and the resulting polymer microstructure and
      other characteristics. In the second part of this review we present studies that
      have used solid-state NMR to investigate the composition of Ziegler-Natta and
      metallocene catalysts or the interactions between their components. 

PMID- 25957881
TI  - Effect of diagnostic testing on medicines used by febrile children less than five
      years in 12 malaria-endemic African countries: a mixed-methods study.
AB  - BACKGROUND: In 2010, WHO revised guidelines to recommend testing all suspected
      malaria cases prior to treatment. Yet, evidence to assess programmes is largely
      derived from limited facility settings in a limited number of countries. National
      surveys from 12 sub-Saharan African countries were used to examine the effect of
      diagnostic testing on medicines used by febrile children under five years at the
      population level, including stratification by malaria risk, transmission season,
      source of care, symptoms, and age. METHODS: Data were compiled from 12
      Demographic and Health Surveys in 2010-2012 that reported fever prevalence,
      diagnostic test and medicine use, and socio-economic covariates (n=16,323 febrile
      under-fives taken to care). Mixed-effects logistic regression models quantified
      the influence of diagnostic testing on three outcomes (artemisinin combination
      therapy (ACT), any anti-malarial or any antibiotic use) after adjusting for data
      clustering and confounding covariates. For each outcome, interactions between
      diagnostic testing and the following covariates were separately tested: malaria
      risk, season, source of care, symptoms, and age. A multiple case study design was
      used to understand varying results across selected countries and sub-national
      groups, which drew on programme documents, published research and expert
      consultations. A descriptive typology of plausible explanations for quantitative
      results was derived from a cross-case synthesis. RESULTS: Significant variability
      was found in the effect of diagnostic testing on ACT use across countries (e.g.,
      Uganda OR: 0.84, 95% CI: 0.66-1.06; Mozambique OR: 3.54, 95% CI: 2.33-5.39). Four
      main themes emerged to explain results: available diagnostics and medicines;
      quality of care; care-seeking behaviour; and, malaria epidemiology. CONCLUSIONS:
      Significant country variation was found in the effect of diagnostic testing on
      paediatric fever treatment at the population level, and qualitative results
      suggest the impact of diagnostic scale-up on treatment practices may not be
      straightforward in routine conditions given contextual factors (e.g., access to
      care, treatment-seeking behaviour or supply stock-outs). Despite limitations,
      quantitative results could help identify countries (e.g., Mozambique) or issues
      (e.g., malaria risk) where facility-based research or programme attention may be
      warranted. The mixed-methods approach triangulates different evidence to
      potentially provide a standard framework to assess routine programmes across
      countries or over time to fill critical evidence gaps.

PMID- 25957883
TI  - Immobilization antigen vaccine adjuvanted by parasitic heat shock protein 70C
      confers high protection in fish against cryptocaryonosis.
AB  - The immobilization antigen (iAg) has been demonstrated as a protective immunogen
      against Cryptocaryon irritans infection. In this study, C-terminal domain of heat
      shock protein 70 cloned from C. irritans (Hsp70C) was tested for its immuno
      stimulatory effects. The iAg and Hsp70C cDNAs were constructed independently in
      secretory forms and were encapsulated in chitosan nanoparticles. In the first
      immunization trial, grouper fingerlings orally intubated with iAg and iAg:Hsp70C
      presented 96% and 100% relative percent survival (RPS), respectively, after a
      lethal challenge. In the second trial, both iAg and iAg:Hsp70C groups showed 100%
      RPS and the skin trophont burden was significantly lowered. The iAg:Hsp70C still
      provides a significantly high protection of 51% RPS at 49 days post immunization,
      when an even more serious lethal infection occurs. RT-qPCR results showed that
      Hsp70C could up-regulate the expression of i) T cell markers: Cluster of
      Differentiation 8 alpha (CD8alpha) and CD4, ii) cytokine genes: Interferon gamma
      (IFNgamma), Tumor Necrosis Factor alpha (TNFalpha) and Interleukin 12 p40 (IL
      12/P40), iii) antibody genes: Immunoglobulin M heavy chain (IgMH) and IgTH, and
      iv) major histocompatibility complex (MHC-I & MHC-II), in the spleen of
      iAg:Hsp70C group. Furthermore, significantly high levels of iAg-specific IgM was
      detected in skin mucus which efficiently immobilized live theronts in iAg- and
      iAg:Hsp70C-immunized fish at 5 weeks post immunization. Hsp70C significantly
      increased the number of nonspecific CD8(+) skin leucocytes which exerted
      cytotoxicity against theronts, although cytotoxic activity showed no difference
      among the various groups. Because of this complementary cooperation of cellular
      and humoral immune responses, Hsp70C enhances the efficacy of iAg vaccine and
      constrains C. irritans infection. In view of the severe loss caused by
      cryptocaryonosis, application of this parasitic vaccine in farmed and ornamental
      fish, is worthy to be considered.

PMID- 25957884
TI  - Liver functional metabolomics discloses an action of L-leucine against
      Streptococcus iniae infection in tilapias.
AB  - Streptococcus iniae seriously affects the intensive farming of tilapias. Much
      work has been conducted on prevention and control of S. iniae infection, but
      little published information on the metabolic response is available in tilapias
      against the bacterial infection, and no metabolic modulation way may be adopted
      to control this disease. The present study used GC/MS based metabolomics to
      characterize the metabolic profiling of tilapias infected by a lethal dose (LD50)
      of S. iniae and determined two characteristic metabolomes separately responsible
      for the survival and dying fishes. A reversal changed metabolite, decreased and
      increased l-leucine in the dying and survival groups, respectively, was
      identified as a biomarker which featured the difference between the two
      metabolomes. More importantly, exogenous l-leucine could be used as a metabolic
      modulator to elevate survival ability of tilapias infected by S. iniae. These
      results indicate that tilapias mount metabolic strategies to deal with bacterial
      infection, which can be regulated by exogenous metabolites such as l-leucine. The
      present study establishes an alternative way, metabolic modulation, to cope with
      bacterial infections. 

PMID- 25957885
TI  - Immunolocalization of tumor necrosis factor alpha in turbot (Scophthalmus
      maximus, L.) tissues.
AB  - Tumor necrosis factor alpha (TNFalpha) is a cytokine involved in a broad spectrum
      of cellular and organismal responses. Its main function, as a potent pro
      inflammatory mediator, has been demonstrated in numerous teleost species and
      there are many reports on the modulation of TNFalpha gene expression under
      pathological conditions. Nevertheless, there is still scarce knowledge about the
      tissue distribution and type of cells that express this cytokine in fish species,
      which would help to further investigate its biological activities. These studies
      are hampered by the lack of molecular markers for teleost that hinder the
      development of morphological techniques, like immunohistochemistry. The aim of
      this work was to develop an immunohistochemical technique for the detection of
      TNFalpha in paraffin-embedded organs from healthy turbot (Scophthalmus maximus),
      an economically-important marine fish species. A commercial anti-human TNFalpha
      antibody, whose specificity was confirmed by western blot analysis, was used.
      Immunoreactive cells were observed in higher numbers in the lymphohematopoietic
      organs, kidney, spleen and thymus, although TNFalpha-positive cells were also
      present in the digestive tract, liver, heart, gills and skin. Similarly to non
      fish species, monocytes/macrophages appeared to be the main producers of this
      cytokine; nevertheless, the presence of immunoreactive rodlet cells in different
      tissues was also reported. The nature and distribution of the labeled cells
      appeared to be related with a strategic localization for defense response to
      antigenic challenge. The relative abundance of TNFalpha-positive cells in the
      lymphohematopoietic organs also suggests that this cytokine may have a broader
      role in the normal physiology of those organs. The immunohistochemical technique
      allowed the in-situ characterization of TNFalpha expression, representing a valid
      tool to investigate the immune response of turbot. 

PMID- 25957886
TI  - Dietary pantothenic acid deficiency and excess depress the growth, intestinal
      mucosal immune and physical functions by regulating NF-kappaB, TOR, Nrf2 and MLCK
      signaling pathways in grass carp (Ctenopharyngodon idella).
AB  - This study investigated the effects of dietary pantothenic acid (PA) on the
      growth, intestinal mucosal immune and physical barrier, and relative mRNA levels
      of signaling molecules in the intestine of grass carp (Ctenopharyngodon idella).
      A total of 540 grass carp (253.44 +/- 0.69 g) were fed six diets with graded
      levels of PA (PA1, PA15, PA30, PA45, PA60 and PA75 diets) for 8 weeks. The
      results indicated that compared with PA deficiency (PA1 diet) and excess (PA75
      diet) groups, optimal PA supplementation increased (P < 0.05): (1) percent weight
      gain (PWG), feed intake and feed efficiency; (2) lysozyme activity, complement 3
      content, liver-expressed antimicrobial peptide 2 and hepcidin, interleukin 10,
      transforming growth factor beta1 and inhibitor of kappaBalpha mRNA levels in some
      intestinal segments; (3) activities and mRNA levels of copper/zinc superoxide
      dismutase, manganese superoxide dismutase, catalase, glutathione peroxidase,
      glutathione S-transferases and glutathione reductase, and NF-E2-related factor 2
      (Nrf2) mRNA level in the whole intestine; (4) Claudin b, Claudin 3, Claudin c,
      Occludin and ZO-1 mRNA levels in some intestinal segments of grass carp.
      Conversely, optimal PA supplementation decreased (P < 0.05): (1) tumor necrosis
      factor alpha, interleukin 1beta, interferon gamma2, interleukin 8, nuclear factor
      kappaB P65 (NF-kappaB P65), IkappaB kinase alpha, IkappaB kinase beta, IkappaB
      kinase gamma and target of rapamycin (TOR) mRNA expression levels in some
      intestinal segments; (2) reactive oxygen species, malondialdehyde and protein
      carbonyl contents, and Kelch-like ECH-associating protein 1a, Kelch-like ECH
      associating protein 1b in the intestine; (3) Claudin 12, Claudin 15a and myosin
      light-chain kinase (MLCK) mRNA levels in some intestinal segments of grass carp.
      In conclusion, optimum PA promoted growth, intestinal mucosal immune and physical
      function, as well as regulated mRNA levels of signaling molecules NF-kappaB P65,
      TOR, Nrf2 and MLCK in grass carp intestine. Based on the quadratic regression
      analysis of PWG and intestinal lysozyme activity, the optimal PA levels in grass
      carp (253.44-745.25 g) were estimated to be 37.73 mg/kg and 41.38 mg/kg diet,
      respectively.

PMID- 25957887
TI  - Prospective study of serum uric acid levels and incident metabolic syndrome in a
      Korean rural cohort.
AB  - OBJECTIVE: Recent studies have demonstrated an association between serum uric
      acid (SUA) levels and metabolic syndrome (MetS). However, paucity of available
      data regarding the cause and effect relationship between SUA and MetS in healthy
      adults is still a big challenge which remains to be studied. Therefore, we
      investigated whether SUA predicts new onset of MetS in a population-based cohort
      study. METHODS: The study included 1590 adults (661 men and 929 women) aged 40-70
      years without MetS at baseline (2005-2008) and subjects were prospectively
      followed for 2.6 years. To evaluate the relationship between SUA and MetS, we
      divided the aforementioned subjects into quintiles (SUA-I to SUA-V) from the
      lowest to the highest values of SUA. SUA was measured by the enzymatic
      colorimetric method. We used category-free net reclassification improvement (NRI)
      and integrated discrimination improvement (IDI) to characterize the performance
      of predicted model. RESULTS: During a mean of 2.6 years of follow-up, 261(16.4%)
      adults developed MetS. MetS variables were significantly related to the baseline
      SUA level. Waist circumference (WC), blood pressure (BP), and serum triglyceride
      (TG) were significantly higher in the highest quintile of SUA compared to the
      lowest SUA quintile in men and women. After adjustment for age, total cholesterol
      and low-density lipoprotein cholesterol (LDL-C) in men and women, subjects in the
      fifth quintiles of SUA showed significantly higher ORs for incident MetS. The
      association between hyperuricemia and new onset of MetS were consistently
      stronger in women than men. Additionally, among women, we found an improvement in
      the area under the ROC curve in the models that added SUA to core components of
      MetS. CONCLUSION: Our study suggests that SUA is significantly correlated with
      future risk of WC, BP, TG and may predicted as a risk factor for developing MetS.
      SUA may have a clinical role in predicting new-onset metabolic syndrome among
      women. Large prospective study is needed to reveal the clinical significance of
      SUA in metabolic disease.

PMID- 25957888
TI  - All-trans retinoic acid up-regulates the human CD2AP gene expression through
      Sp1/Sp3 binding sites.
AB  - All-trans retinoic acid (ATRA), an active metabolite of vitamin A, plays an
      important role in regulating cell differentiation, proliferation, and apoptosis.
      It was reported that ATRA could cause an up-regulation of protein expression of
      CD2AP in nephrotic animals. However, the mechanism of ATRA-mediated up-regulation
      is not well understood. In the present study, deletion analysis and luciferase
      assays demonstrated that ATRA caused a marked increase in the activity of the
      CD2AP promoter, and the region between nt -599 and -328 from the transcription
      start site, where there are two clusters of Sp1/3 binding sites, was
      indispensable for ATRA-mediated up-regulation. Chromatin immunoprecipitation
      assays revealed that ATRA activated the CD2AP transcription through enhancing the
      DNA-binding activity of Sp1 and Sp3 with the CD2AP promoter. Taken together, this
      study provided evidence for the first time showing the stimulating effect of ATRA
      on CD2AP and new therapeutic strategies for the treatment of nephritic syndrome
      and other associated diseases of CD2AP deficiency. 

PMID- 25957889
TI  - Induction of a Th1 immune response and suppression of IgE via immunotherapy with
      a recombinant hybrid molecule encapsulated in liposome-protamine-DNA
      nanoparticles in a model of experimental allergy.
AB  - Liposome-protamine-DNA nanoparticles (LPD) are safe, effective, and non-toxic
      adjuvants that induce Th1-like immune responses. We hypothesized that
      encapsulation of allergens into liposomes could be an appropriate option for
      immunotherapy. The present study evaluated the immunotherapeutic potential of a
      recombinant hybrid molecule (rHM) encapsulated in LPD nanoparticles in a murine
      model of Chenopodium album allergy. BALB/c mice were sensitized with the allergen
      in alum, and the immunotherapy procedure was performed by subcutaneous injections
      of LPD-rHM, rHM, or empty LPD at weekly intervals. Sensitized mice developed a
      Th2-biased immune response characterized by strong specific IgG1 and IgE
      production, IL-4, and the transcription factor GATA3 in spleen cell cultures.
      Treatment with the LPD-rHM resulted in a reduction in IgE and a marked increase
      in IgG2a. The LPD-rHM induced allergen-specific responses with relatively high
      interferon-gamma production, as well as expression of the transcription factor T
      bet in stimulated splenocytes. In addition, lymphoproliferative responses were
      higher in the LPD-rHM-treated mice than in the other groups. Removal of the
      nanoparticles from the rHM resulted in a decrease in the allergen's
      immunogenicity. These results indicate that the rHM complexed with LPD
      nanoparticles has a marked suppressive effect on the allergic response and caused
      a shift toward a Th1 pathway. 

PMID- 25957890
TI  - Clinical significance of day 5 peripheral blast clearance rate in the evaluation
      of early treatment response and prognosis of patients with acute myeloid
      leukemia.
AB  - BACKGROUND: Minimal residual disease detection in the bone marrow is usually
      performed in patients with acute myeloid leukemia undergoing one course of
      induction chemotherapy. To optimize the chemotherapy strategies, more practical
      and sensitive markers are needed to monitor the early treatment response during
      induction. For instance, peripheral blood (PB) blast clearance rate may be
      considered as such a monitoring marker. METHODS: PB blasts were monitored through
      multiparameter flow cytometry (MFC). Absolute counts were determined before
      treatment (D0) and at specified time points of induction chemotherapy (D3, D5,
      D7, and D9). The cut-off value of D5 peripheral blast clearance rate (D5-PBCR)
      was defined through receiver operating characteristic (ROC) analysis. Prognostic
      effects were compared among different patient groups according to D5-PBCR cut-off
      value. RESULTS: D5-PBCR cut-off value was determined as 99.55%. Prognostic
      analysis showed that patients with D5-PBCR >=99.55% more likely achieved complete
      remission (94.6% vs. 56.1%, P < 0.001) and maintained a relapse-free status than
      other patients (80.56% vs. 57.14%, P = 0.027). Survival analysis revealed that
      relapse-free survival (RFS) and overall survival (OS) were longer in patients
      with D5-PBCR >=99.55% than in other patients (two-year OS: 71.0% vs. 38.7%, P =
      0.011; two-year RFS: 69.4% vs. 30.7%, P = 0.026). In cytogenetic-molecular
      intermediate-risk group, a subgroup with worse outcome could be distinguished on
      the basis of D5-PBCR (<99.55%; OS: P = 0.033, RFS: P = 0.086). CONCLUSIONS: An
      effective evaluation method of early treatment response was established by
      monitoring PB blasts through MFC. D5-PBCR cut-off value (99.55%) can be a
      reliable reference to predict treatment response and outcome in early stages of
      chemotherapy. The proposed marker may be used in induction regimen modification
      and help optimize cytogenetic-molecular prognostic risk stratification.

PMID- 25957891
TI  - Influence of BCL2-938C>A and BAX-248G>A promoter polymorphisms in the development
      of AML: case-control study from South India.
AB  - B-cell lymphoma 2 (BCL2) and BCL2-associated X protein (BAX) proteins are anti
      apoptotic and pro-apoptotic determinants of mitochondrial-mediated apoptosis, and
      their relative expression determines the cell fate. The promoter polymorphisms in
      these genes were shown to alter the protein function or expression and exert an
      impact on apoptosis regulation. Deregulation in the expression of any of these
      genes leads to disruption of cellular homeostasis and malignant transformation.
      The present study was aimed to determine the association of BCL2-938C>A and BAX
      248G>A promoter polymorphisms with origin and progression of acute myeloid
      leukemia (AML). We also have performed combined genotype analysis to evaluate the
      cumulative effect of risk genotypes in the AML development. These polymorphisms
      were genotyped by polymerase chain reaction- restriction fragment length
      polymorphism (PCR-RFLP) in 221 AML patients and 305 age- and sex-matched healthy
      controls. Our study revealed that BCL2-938CA (p = 0.018) and BAX-248GG (0.043)
      genotypes were significantly associated with increased risk for AML occurrence.
      BAX-248A allele had shown decreased risk for AML. The combined analysis had shown
      that BCL2-938CA+AA-BAX-248GG group had a 1.63-fold (95 % CI: 1.08-2.45, p = 0.02)
      increased risk for AML. None of the clinical variables had shown any significant
      association with both polymorphisms. With respect to complete remission (CR)
      rate, BAX-248GG genotype (p = 0.002) and G allele (p = 0.009) had conferred
      significant risk for complete remission failure. Although the log rank test was
      not significant, survival analysis had shown a trend where BCL2-938CA genotype,
      and BAX-248GG had reduced median disease-free survival (DFS) of 9 and 10 months,
      respectively. In conclusion, BCL2-938C>A and BAX-248G>A gene polymorphisms might
      contribute to the origin of AML. Moreover, influence of BAX-248GG genotype on CR
      and DFS rate suggests that the BAX-248G>A polymorphism can serve as marker for
      poor prognosis in AML.

PMID- 25957892
TI  - Treatment of Dutch rat models of glioma using EphrinA1-PE38/GM-CSF chitosan
      nanoparticles by in situ activation of dendritic cells.
AB  - Although dendritic cells (DCs) used in DC-based immunotherapy are loaded with
      tumor-associated antigens, the antitumor immune response is effectively
      stimulated in cytotoxic specific T lymphocytes (CTLs), thereby achieving targeted
      killing of tumor cells without harming surrounding normal cells. This makes it a
      highly promising new form of therapy. In this study, we successfully created
      chitosan-coated EphrinA1-PE38/GM-CSF nanoparticles and transplanted them into
      tumor-bearing rats, resulting in the effective killing of glioma tissue and a
      prolonged life span. Further immunohistochemistry and flow cytometry studies
      revealed that the treatment was effective in increasing the number of dendritic
      cell activations under an immunomodulatory response. These results suggest that
      chitosan-coated EphrinA1-PE38/GM-CSF nanoparticles may be effective in inducing
      in situ activation of DCs in glioma-bearing rats, thereby generating DC vaccines
      in vivo.

PMID- 25957894
TI  - Seroprevalence of measles and rubella virus antibodies in the population of the
      Community of Madrid, 2008-2009.
AB  - The seroprevalence (SP) of measles and rubella virus antibodies is presented by
      age groups obtained in the IV Serosurvey of the Region of Madrid (2008-2009). The
      target population is composed of residents with ages ranging between 2 and 60
      years in the Region of Madrid. A two-stage cluster sample is used. The SP of
      measles virus antibodies is 97.8% (CI 95%: 97.3-98.2). The highest SP is observed
      in the 2-5 year and 41-60 year age groups. The point estimate does not reach 95%
      in the 16-20 and 21-30 year age groups. The SP of rubella virus antibodies is
      97.2% (CI 95%: 96.5-97.7). The SP is over 95% in all of the age groups. In
      immigrant women between the ages of 16 and 49, the SP is 95.9% (CI 95%: 93.7
      97.4). The identification of groups susceptible to the measles virus in young
      adults could lead to outbreaks as a result of importing the virus. The
      circulation of the rubella virus is possible among immigrant women aged between
      16 and 49 years, which could lead to the appearance of SRC cases. Epidemiological
      surveillance will allow the impact on the measles and rubella elimination plan to
      be determined in the future. 

PMID- 25957895
TI  - Haunting the HOXA Locus: Two Faces of lncRNA Regulation.
AB  - Long non-coding RNAs (lncRNAs) regulate diverse biological functions through
      mechanisms ascribed to the lncRNA transcript itself. Now in Cell Stem Cell, Yin
      et al. (2015) use CRISPR/Cas9-mediated genome editing to demonstrate discrete and
      opposing roles for the lncRNA Haunt transcript and DNA at the HOXA locus during
      ESC differentiation. 

PMID- 25957893
TI  - Career plans of primary care midwives in the Netherlands and their intentions to
      leave the current job.
AB  - BACKGROUND: In labour market policy and planning, it is important to understand
      the motivations of people to continue in their current job or to seek other
      employment. Over the last decade, besides the increasingly medical approach to
      pregnancy and childbirth and decreasing home births, there were additional
      dramatic changes and pressures on primary care midwives and midwifery care.
      Therefore, it is important to re-evaluate the career plans of primary care
      midwives and their intentions to leave their current job. METHODS: All 108
      primary care midwives of 20 selected midwifery care practices in the Netherlands
      were invited to fill out a written questionnaire with questions regarding career
      plans and intentions to leave. Bivariate analyses were carried out to compare
      career plans and work-related and personal characteristics and attitudes towards
      work among the group of midwives who indicated that they intended to leave their
      current job (ITL group) and those who indicated they had no intention to leave
      (NITL group). Significant predictors of ITL were included in the multiple binary
      logistic regression with 'intention to leave' as the dependent variable. RESULTS:
      In 2010, 32.7% of the 98 participating primary care midwives surveyed had
      considered an intention to leave their current type of job in the past year.
      Fewer ITL midwives wanted to be a self-employed practitioner with the full range
      of primary care tasks and work full-time. Significant predictors of the primary
      care midwives' intention to leave included a lower overall score on the job
      satisfaction scale (OR = 0.18; 95% CI = 0.06-0.58; p = 0.004) and being between
      30 and 45 years old (OR = 2.69; 95% CI = 1.04-7.0; p = 0.041). CONCLUSION: Our
      study shows that, despite significant changes in the reproductive, maternal and
      newborn health service delivery that impact on independent midwifery practice,
      the majority of primary care midwives intended to stay in primary care. The
      absence of job satisfaction, and being in the age group between 30 and 45 years
      old, is associated with primary care midwives' intention to leave their current
      job. Ongoing monitoring will be important in the future.

PMID- 25957896
TI  - Pushing and pulling on adult neural stem cells.
AB  - How plastic is adult neurogenesis? In this issue of Cell Stem Cell, Sierra et al.
      (2015) use epilepsy models to probe how hippocampal neural stem cells (NSCs)
      respond to graded pathological conditions. They uncover changes in cell fate
      potential upon NSC activation, but it comes at a cost. 

PMID- 25957898
TI  - What Endothelial Cells from Patient iPSCs Can Tell Us about Aortic Valve Disease.
AB  - In a recent issue of Cell, Theodoris et al. (2015) used a complex systems biology
      approach to model vascular aortic calcification caused by mutations in the NOTCH1
      gene. Comparison of endothelial cells from patient hiPSCs and genetically matched
      controls under fluid flow revealed novel mechanisms underlying the disease. 

PMID- 25957897
TI  - Forces of Change: Mechanics Underlying Formation of Functional 3D Organ Buds.
AB  - 3D organ buds that can recapitulate organ function have myriad applications for
      regenerative and personalized medicine. Here, Takebe et al. (2015) describe a
      generalized method for organ bud formation, demonstrating that mechanosensitive
      mesenchymal stem cells drive condensation of heterotypic cell mixtures to create
      buds from diverse organs. 

PMID- 25957899
TI  - Converting a Problem into an Opportunity: mtDNA Heteroplasmy Shift.
AB  - The transmission of mitochondrial DNA (mtDNA) disease from a mother with a
      heteroplasmic mtDNA mutation to her children is unpredictable. In a recent issue
      of Cell, Reddy et al. (2015) present the potential for mitochondrial-targeted
      nucleases to remove mutated mtDNA through the induction of heteroplasmy shift in
      oocytes and zygotes. 

PMID- 25957900
TI  - Of Mice and Man: Differential DNMT Dependence in Mammalian ESCs.
AB  - Liao et al. (2015) recently reported on the effects of disrupting DNA
      methyltransferase activity in human embryonic stem cells (hESCs). This work
      highlights key differences between mammalian ESC models upon the loss of these
      essential proteins and provides comprehensive base resolution methylome maps of
      DNMT targets during human development. 

PMID- 25957901
TI  - Stem cell patents after the america invents act.
AB  - Under the newly passed Leahy-Smith America Invents Act (AIA), the U.S. Patent and
      Trademark Office may hear new challenges to stem cell patents. Here, we explore
      how the new law affects challenges to stem cell patents, focusing on two recent
      cases, and discuss the future of stem cell patent disputes. 

PMID- 25957902
TI  - Stem cell heterogeneity and plasticity in epithelia.
AB  - Epithelia cover the surfaces and line the cavities of the body. Recent studies
      have highlighted the existence of multiple stem cell compartments within
      individual epithelia that exhibit striking plasticity in response to tissue
      damage, transplantation, or tumor development. New knowledge about the
      composition of the epithelial niche and the transcription factor networks that
      maintain cell identity has provided new insights into the extrinsic and intrinsic
      regulation of stem cell behavior. In addition new in vitro tissue substitutes
      allow better integration of data from human and mouse models.

PMID- 25957905
TI  - New trends in guided nanotherapies for digestive cancers: A systematic review.
AB  - Digestive tract tumors are among the most common and deadliest malignancies
      worldwide, mainly due to late diagnosis and lack of efficient therapeutics.
      Current treatments essentially rely on surgery associated with (neo)adjuvant
      chemotherapy agents. Despite an upfront response, conventional drugs often fail
      to eliminate highly aggressive clones endowed with chemoresistant properties,
      which are responsible for tumor recurrence and disease dissemination. Synthetic
      drugs also present severe adverse systemic effects, hampering the administration
      of biologically effective dosages. Nanoencapsulation of chemotherapeutic agents
      within biocompatible polymeric or lipid matrices holds great potential to improve
      the pharmacokinetics and efficacy of conventional chemotherapy while reducing
      systemic toxicity. Tagging nanoparticle surfaces with specific ligands for cancer
      cells, namely monoclonal antibodies or antibody fragments, has provided means to
      target more aggressive clones, further improving the selectivity and efficacy of
      nanodelivery vehicles. In fact, over the past twenty years, significant research
      has translated into a wide array of guided nanoparticles, providing the molecular
      background for a new generation of intelligent and more effective anti-cancer
      agents. Attempting to bring awareness among the medical community to emerging
      targeted nanopharmaceuticals and foster advances in the field, we have conducted
      a systematic review about this matter. Emphasis was set on ongoing preclinical
      and clinical trials for liver, colorectal, gastric and pancreatic cancers. To the
      best of our knowledge this is the first systematic and integrated overview on
      this field. Using a specific query, 433 abstracts were gathered and narrowed to
      47 manuscripts when matched against inclusion/exclusion criteria. All studies
      showed that active targeting improves the effectiveness of the nanodrugs alone,
      while lowering its side effects. The main focus has been on hepatocarcinomas,
      mainly by exploring glycans as homing molecules. Other ligands such as
      peptides/small proteins and antibodies/antibody fragments, with affinity to
      either tumor vasculature or tumor cells, have also been widely and successfully
      applied to guide nanodrugs to gastrointestinal carcinomas. Conversely, few
      solutions have been presented for pancreatic tumors. To this date only three
      nanocomplexes have progressed beyond pre-clinical stages: i) PK2, a galactosamine
      functionalized polymeric-DOX formulation for hepatocarcinomas; ii) MCC-465, an
      anti-(myosin heavy chain a) immunoliposome for advanced stage metastatic solid
      tumors; and iii) MBP-426, a transferrin-liposome-oxaliplatin conjugate, also for
      advanced stage tumors. Still, none has been approved for clinical use. However,
      based on the high amount of pre-clinical studies showing enthusiastic results,
      the number of clinical trials is expected to increase in the near future. A more
      profound understanding about the molecular nature of chemoresistant clones and
      cancer stem cell biology will also contribute to boost the field of guided
      nanopharmacology towards more effective solutions. 

PMID- 25957903
TI  - Myocardial Infarction Activates CCR2(+) Hematopoietic Stem and Progenitor Cells.
AB  - Following myocardial infarction (MI), myeloid cells derived from the
      hematopoietic system drive a sharp increase in systemic leukocyte levels that
      correlates closely with mortality. The origin of these myeloid cells, and the
      response of hematopoietic stem and progenitor cells (HSPCs) to MI, however, is
      unclear. Here, we identify a CCR2(+)CD150(+)CD48(-) LSK hematopoietic subset as
      the most upstream contributor to emergency myelopoiesis after ischemic organ
      injury. This subset has 4-fold higher proliferation rates than CCR2(
      )CD150(+)CD48(-) LSK cells, displays a myeloid differentiation bias, and
      dominates the migratory HSPC population. We further demonstrate that the myeloid
      translocation gene 16 (Mtg16) regulates CCR2(+) HSPC emergence. Mtg16(-/-) mice
      have decreased levels of systemic monocytes and infarct-associated macrophages
      and display compromised tissue healing and post-MI heart failure. Together, these
      data provide insights into regulation of emergency hematopoiesis after ischemic
      injury and identify potential therapeutic targets to modulate leukocyte output
      after MI. 

PMID- 25957906
TI  - Engineering of a novel adjuvant based on lipid-polymer hybrid nanoparticles: A
      quality-by-design approach.
AB  - The purpose of this study was to design a novel and versatile adjuvant intended
      for mucosal vaccination based on biodegradable poly(DL-lactic-co-glycolic acid)
      (PLGA) nanoparticles (NPs) modified with the cationic surfactant
      dimethyldioctadecylammonium (DDA) bromide and the immunopotentiator trehalose
      6,6'-dibehenate (TDB) (CAF01) to tailor humoral and cellular immunity
      characterized by antibodies and Th1/Th17 responses. Such responses are important
      for the protection against diseases caused by intracellular bacteria such as
      Chlamydia trachomatis and Mycobacterium tuberculosis. The hybrid NPs were
      engineered using an oil-in-water single emulsion method and a quality-by-design
      approach was adopted to define the optimal operating space (OOS). Four critical
      process parameters (CPPs) were identified, including the acetone concentration in
      the water phase, the stabilizer [polyvinylalcohol (PVA)] concentration, the lipid
      to-total solid ratio, and the total concentration. The CPPs were linked to
      critical quality attributes consisting of the particle size, polydispersity index
      (PDI), zeta-potential, thermotropic phase behavior, yield and stability. A
      central composite face-centered design was performed followed by multiple linear
      regression analysis. The size, PDI, enthalpy of the phase transition and yield
      were successfully modeled, whereas the models for the zeta-potential and the
      stability were poor. Cryo-transmission electron microscopy revealed that the main
      structural effect on the nanoparticle architecture is caused by the use of PVA,
      and two different morphologies were identified: i) A PLGA core coated with one or
      several concentric lipid bilayers, and ii) a PLGA nanoshell encapsulating lipid
      membrane structures. The optimal formulation, identified from the OOS, was
      evaluated in vivo. The hybrid NPs induced antibody and Th1/Th17 immune responses
      that were similar in quality and magnitude to the response induced by DDA/TDB
      liposomes, showing that the adjuvant properties of DDA/TDB are maintained in the
      PLGA hybrid matrix. This study demonstrates the complexity of formulation design
      for the engineering of a hybrid lipid-polymer nanoparticle adjuvant. 

PMID- 25957904
TI  - Neuronal hyperactivity accelerates depletion of neural stem cells and impairs
      hippocampal neurogenesis.
AB  - Adult hippocampal neurogenesis is believed to maintain a range of cognitive
      functions, many of which decline with age. We recently reported that radial
      neural stem cells (rNSCs) in the hippocampus undergo activation-dependent
      conversion into astrocytes, a mechanism that over time contributes to a reduction
      in the rNSC population. Here, we injected low and high levels of kainic acid (KA)
      in the dentate gyrus to assess whether neuronal hyperexcitation, a hallmark of
      epileptic disorders, could accelerate this conversion. At low levels of KA,
      generating epileptiform activity without seizures, we indeed found increased rNSC
      activation and conversion into astrocytes. At high levels, generating sustained
      epileptic seizures, however, we find that rNSCs divide symmetrically and that
      both mother and daughter cells convert into reactive astrocytes. Our results
      demonstrate that a threshold response for neuronal hyperexcitation provokes a
      dramatic shift in rNSC function, which impairs adult hippocampal neurogenesis in
      the long term. 

PMID- 25957907
TI  - Xenopus laevis oocyte maturation is affected by metal chlorides.
AB  - Few studies have been conducted using Xenopus laevis germ cells as oocytes,
      though these cells offer many advantages allowing both electrophysiological
      studies and morphological examination. Our aim was to investigate the effects of
      metal (cadmium, lead, cobalt and zinc) exposures using cell biology approaches.
      First, cell survival was evaluated with both phenotypical and
      electrophysiological approaches. Secondly, the effect of metals on oocyte
      maturation was assessed with morphological observations and electrophysiological
      recordings. From survival experiments, our results showed that metal chlorides
      did not affect cell morphology but strongly depolarized X. laevis oocyte resting
      potential. In addition, cadmium chloride was able to inhibit progesterone-induced
      oocyte maturation. By contrast, zinc, but also to a lesser extent cadmium, cobalt
      and lead, were able to enhance spontaneous oocyte maturation in the absence of
      progesterone stimulation. Finally, electrophysiological recordings revealed that
      some metal chlorides (lead, cadmium) exposures could disturb calcium signaling in
      X. laevis oocyte by modifying calcium-activated chloride currents. Our results
      demonstrated the high sensitivity of X. laevis oocytes toward exogenous metals
      such as lead and cadmium. In addition, the cellular events recorded might have a
      predictive value of effects occurring later on the ability of oocytes to be
      fertilized. Together, these results suggest a potential use of this cellular lab
      model as a tool for ecotoxicological assessment of contaminated fresh waters. 

PMID- 25957908
TI  - Biomarker Discovery in Cerebral Vasospasm after Aneurysmal Subarachnoid
      Hemorrhage.
AB  - BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating problem.
      Overall, the mortality rate associated with aSAH is 32% to 67%, which makes it
      the most lethal type of hemorrhagic stroke. Once the aneurysm has been treated,
      cerebral vasospasm is the leading cause of morbidity and mortality associated
      with aSAH. Thus, ability to effectively prevent or treat cerebral vasospasm could
      result in significantly improved survival and quality of life for aSAH patients.
      Unfortunately, partly because of poor understanding of the mechanisms of
      vasospasm, current diagnosis and treatment can be inconsistent and/or
      ineffective. Current treatment methods include primarily medical therapy and
      endovascular methods. Alone, or in combination, these measures can be of benefit
      in some patients. However, they are not uniformly efficacious and, on an
      individual basis, they can present significant risks. These risks include stroke,
      cardiovascular compromise, and death. More effective diagnosis and treatment
      strategies could significantly improve patient outcomes after aSAH.
      Unfortunately, clinically reliable biomarker for cerebral vasospasm has yet to be
      identified. Biomarker discovery may facilitate earlier diagnosis of vasospasm and
      improved monitoring of the response to treatment. It may help in stratifying
      patients into categories of risk to develop vasospasm, which could subsequently
      guide therapy. Indeed, biomarker research may suggest "vasospasm phenotypes" that
      can be used to guide the most effective type of therapy for that particular
      patient. The purpose of this manuscript is to review the current cerebral
      vasospasm biomarker literature. METHODS: An extensive PubMed literature search
      was performed. We identified over 100 English language articles with key words
      cerebral vasospasm and biomarkers. Some of these articles and related references
      were used as the basis of this review. We focused on related human studies
      performed within the past 10 years. RESULTS: In this review, we focus on recent
      work identifying molecular markers of cerebral vasospasm following aSAH and the
      current understanding of the utility of these markers. We highlight novel
      approaches such as the use of cellular microparticles for the evaluation of
      cerebral vasospasm. CONCLUSIONS: Although multiple molecules have been proposed,
      no single molecule has been shown to be a clinically reliable biomarker for
      cerebral vasospasm. This is not surprising based on the complex pathogenesis of
      cerebral vasospasm. Indeed, it is unlikely that a single biomarker will be
      clinically effective and reliable for predicting cerebral vasospasm. Instead,
      cerebral vasospasm may be best predicted by a panel of markers and the temporal
      progression of their relative levels after aSAH. Many such candidate molecules
      are reviewed herein and can be categorized as markers of cell damage,
      inflammation, changes in metabolism and vascular tone as well as microparticle
      derived biomarkers. Among these, microparticle-derived biomarkers seem to be
      promising and lend themselves to further study. Biomarker discovery may
      facilitate earlier diagnosis of vasospasm and improved monitoring of the response
      to treatment. Ultimately, it may guide in the development of safer and more
      effective therapies for the most dreaded of aSAH complications.

PMID- 25957909
TI  - COX-2 rs20417 Polymorphism Is Associated with Stroke and White Matter Disease.
AB  - BACKGROUND: To investigate the effect of COX-2 polymorphism and its product,
      prostaglandin E2 (PGE2), on stroke risk in an endemic area for Chagas disease. In
      a separate cohort, to investigate the effect of COX-2 polymorphisms on the total
      burden of cerebral white matter disease. METHODS: Cases were outpatients with
      ischemic stroke; controls were stroke-free subjects from 2 outpatient clinics
      (heart failure and caregivers of a movement disorders clinic). We extracted DNA
      from total blood to investigate the rs20417 COX-2 polymorphism. Serologic tests
      (Enzime-linked immunosorbent assay) were performed to confirm Trypanosoma cruzi
      infection and to quantify PGE2 levels. In the Boston cohort, white matter
      hyperintensity volume (WMHv) was quantified on the admission brain magnetic
      resonance images of subjects with ischemic stroke, who also donated DNA for the
      COX-2 gene region analysis. RESULTS: We studied 44 patients with stroke and 96
      controls (46 with heart failure and 50 caregivers) in the Brazilian cohort; and
      788 stroke patients (302 cardioembolic and 486 noncardioembolic) in the Boston
      cohort. In the Brazilian cohort, rs20417 polymorphism was associated with both
      stroke (P = 5 * 10(-6)) and decreased PGE2 levels (P = 4 * 10(-5)); similarly,
      Chagas was associated with stroke (P = 4 * 10(-3)) and decreased PGE2 levels (P =
      7 * 10(-3)). In the Boston cohort, rs20417 polymorphism was associated with
      increased WMHv among noncardioembolic (P = .037), but not among cardioembolic
      stroke patients. CONCLUSIONS: Variation in COX-2 gene is associated with both
      symptomatic and silent brain cerebrovascular disease. This candidate gene region
      should be tested in population-based samples.

PMID- 25957911
TI  - The role of dopamine in the pursuit of nutritional value.
AB  - Acquiring enough food to meet energy expenditure is fundamental for all
      organisms. Thus, mechanisms have evolved to allow foods with high nutritional
      value to be readily detected, consumed, and remembered. Although taste is often
      involved in these processes, there is a wealth of evidence supporting the
      existence of taste-independent nutrient sensing. In particular, post-ingestive
      mechanisms arising from the arrival of nutrients in the gut are able to drive
      food intake and behavioural conditioning. The physiological mechanisms underlying
      these effects are complex but are believed to converge on mesolimbic dopamine
      signalling to translate post-ingestive sensing of nutrients into reward and
      reinforcement value. Discerning the role of nutrition is often difficult because
      food stimulates sensory systems and post-ingestive pathways in concert. In this
      mini-review, I discuss the various methods that may be used to study post
      ingestive processes in isolation including sham-feeding, non-nutritive
      sweeteners, post-ingestive infusions, and pharmacological and genetic methods.
      Using this structure, I present the evidence that dopamine is sensitive to
      nutritional value of certain foods and examine how this affects learning about
      food, the role of taste, and the implications for human obesity. 

PMID- 25957910
TI  - Local Vasogenic Edema without Cerebral Hyperperfusion after Direct
      Revascularization Surgery for Moyamoya Disease.
AB  - Superficial temporal artery-middle cerebral artery anastomosis is generally used
      as the standard surgical treatment for moyamoya disease to prevent cerebral
      ischemic attacks. Although the main potential complications associated with this
      treatment are cerebral hyperperfusion and ischemia, the adverse impacts of
      revascularization surgery remain unclear. Of the 142 consecutive surgeries for
      moyamoya disease at our hospital from 2008, we herein presented 2 cases of adult
      onset moyamoya disease that manifested local vasogenic edema at the site of
      anastomosis without cerebral hyperperfusion; 1 in a 31-year-old woman presented
      with transient ischemic attack and the other in a 22-year-old man manifested as
      minor completed stroke. Both patients underwent superficial temporal artery
      middle cerebral artery anastomosis, resulting in the formation of a reversible
      high-signal-intensity lesion at the site of anastomosis on T2-weighted images
      along with an increase in apparent diffusion coefficient values, whereas
      diffusion-weighted images showed no changes. Neither hyperperfusion nor
      hypoperfusion, as assessed by single-photon emission computed tomography with N
      isopropyl[123I]-p-iodoamphetamine, was observed postoperatively. In light of the
      increased risk of the further progression of vasogenic edema to intracerebral
      hemorrhage, these patients were treated with prophylactic blood pressure lowering
      and the intravenous infusion of a free radical scavenger. They did not have any
      further cerebrovascular events during the follow-up period. Regional vasogenic
      edema without cerebral hyperperfusion, possibly due to cerebral
      ischemia/reperfusion injury, may be another novel entity that needs to be
      considered as a potential complication after extracranial-intracranial bypass for
      moyamoya disease. Strict postoperative management should be used to avoid
      hemorrhagic transformation. 

PMID- 25957912
TI  - Coordination in oro-pharyngeal biomechanics during human swallowing.
AB  - In swallowing, the tongue contacts against the hard palate to generate pressure
      for propelling a bolus from the oral cavity into the pharynx. Meanwhile, the
      hyoid and larynx move upward and forward to facilitate the bolus from the pharynx
      into the esophagus. It has been well known that sequential coordination between
      those actions is critical for safety accomplishment of swallowing. However, the
      absence of noninvasive assessment for it limits the detection to the
      physiological symptom of dysphagia. We applied a sensor sheet on the hard palate
      to measure tongue contact pressure and a bend sensor on the frontal neck to
      monitor the laryngeal movement, which was synchronized with hyoid motion for
      assessing the coordination between both actions in 14 healthy male subjects when
      swallowing 5ml of water. The sequential order of tongue pressure and hyoid
      movement was successfully displayed. Tongue pressure was produced after slight
      movement of the hyoid and closely to the hyoid elevation, then reached a maximum
      when the hyoid stabilized in the most anterior-superior position, and ceased
      concurrently with the onset of hyoid descent. Additionally, the synchronized data
      from both sensors showed positive correlations between identified time points on
      the laryngeal signal waveform and onset, peak and offset of tongue pressure. Our
      sensing system successfully showed the coordination between tongue pressure
      production and hyoid motion, and could be a simple and noninvasive method for
      clinicians to evaluate the oral and pharyngeal stages of swallowing. 

PMID- 25957913
TI  - Circadian synchronization determines critical day length for seasonal responses.
AB  - A photoperiodic species initiates fat deposition (in migrants) and gonadal
      recrudescence in response to a specific duration of natural daylight, called
      critical day length (CD), when light extends in the inductive phase of the
      endogenous circadian rhythm of photoinducibility (CRP). The molecular basis of
      species-specificCD, determined by the entrainment of the CRP, has been poorly
      understood. To investigate this, we measured expression levels of genes
      implicated in the photoperiod-induced changes in reproduction (EYA3, TSH beta,
      DIO2, DIO3, GNRH and GNIH) and metabolism (SIRT1, HMGCR, FASN and PPAR alpha) in
      photosensitive redheaded buntings subjected to light-dark cycles of varying
      period lengths (T-photocycles). Buntings were exposed to six T22, T24 or T26
      photocycles, with 1h additional light at night falling at different phases of the
      entrained CRP (T2211L=6L:4D:1L:11D; T2411L=6L:4D:1L:13D,T2412L=6L:5D:1L:12D,
      T2413L=6L:6D:1L:11D; T2612L=6L:5D:1L:14D). Photoinduction at genetic and
      phenotypic levels in T2412L and T2413L, not T2411L, groups confirmed CD being
      close to 12h in buntings under T24. Compared to T24, exposure to T22 advanced CD
      by 1h, as evidenced by photoinduction in the T2211L, not T226L, group. Similarly,
      CD appeared to be delayed under T26, with no photoinduction in the T2612L group.
      Further, to show that induction of response under a T-photocycle was because of
      the interaction of inductive phase of the CRP with 1h during the dark period in
      each cycle, not with the 6h main light periods falling 2h earlier each successive
      24hday in a T22 paradigm, a group of buntings was exposed to 6L:16D (T226L), to
      which they did not respond. The mRNA expression of genes, particularly TSH beta,
      DIO2, DIO3 and PPAR alpha, was significantly correlated with changes in
      reproductive and metabolic phenotypes. These results suggest CRP-entrainment
      based genetic regulation of the CD, and extend the idea that synchronization with
      environment is a critical measure in a seasonal species for its temporal
      adaptation in the wild. 

PMID- 25957914
TI  - Downregulation of microRNA-451 in non-alcoholic steatohepatitis inhibits fatty
      acid-induced proinflammatory cytokine production through the AMPK/AKT pathway.
AB  - Mechanisms associated with the progression of non-alcoholic fatty liver disease
      (NAFLD) remain unclear. We attempted to identify the pattern of altered gene
      expression at different time points in a high fat diet (HFD)-induced NAFLD mouse
      model. The early up-regulated genes are mainly involved in the innate immune
      responses, while the late up-regulated genes represent the inflammation
      processes. Although recent studies have shown that microRNAs play important roles
      in hepatic metabolic functions, the pivotal role of microRNAs in the progression
      of NAFLD is not fully understood. We investigated the functions of miR-451, which
      was identified as a target gene in the inflammatory process in NAFLD. miR-451
      expression was significantly decreased in the palmitate (PA)-exposed HepG2 cells
      and in liver tissues of HFD-induced non-alcoholic steatohepatitis (NASH) mice.
      Its decreased expressions were also observed in liver specimens of NASH patients.
      In vitro analysis of the effect of miR-451 on proinflammatory cytokine provided
      evidence for negative regulation of PA-induced interleukin (IL)-8 and tumor
      necrosis factor-alpha (TNF-alpha) production. Furthermore, miR-451 over
      expression inhibited translocation of the PA-induced NF-kappaB p65 subunit into
      the nucleus. Our result showed that Cab39 is a direct target of miRNA-451 in
      steatotic cells. Further study showed that AMPK activated through Cab39 inhibits
      NF-kappaB transactivation induced in steatotic HepG2 cells. miR-451 over
      expression in steatotic cells significantly suppressed PA-induced inflammatory
      cytokine. These results provide new insights into the negative regulation of miR
      451 in fatty acid-induced inflammation via the AMPK/AKT pathway and demonstrate
      potential therapeutic applications for miR-451 in preventing the progression from
      simple steatosis to severely advanced liver disease. 

PMID- 25957915
TI  - The increased Sprouty4 expression in response to serum is transcriptionally
      controlled by Specific protein 1.
AB  - Sprouty proteins control length and intensity of the intracellular signal
      transduction cascade activated by mitogens in the cellular environment. As part
      of a negative feedback loop, their expression is supposed to be elevated by the
      same factors. In this report, Sprouty4 expression in response to serum and the
      underlying regulatory mechanisms were investigated. We verified that Sprouty4
      expression is activated by serum addition in all tested cells independent of
      their origin. Strict correlation between Sprouty4 protein levels and promoter
      activity indicates mainly transcriptional regulation of Sprouty4 serum
      responsiveness. Induction of the mitogen-activated protein kinase pathway is
      required for Sprouty4 promoter activation in the presence of serum. Nonetheless,
      signal transduction via this pathway is not sufficient to fully induce the
      Sprouty4 promoter. Instead, deletion and mutation analysis identified two
      annotated Specific protein 1 binding sites as the critical cis-elements
      responsible for conferring the serum induction of the promoter. Corroborating,
      repressed Specific protein 1 activity or levels result in constitutive lowered
      transcriptional activity of the Sprouty4 promoter. These data demonstrate that
      Specific protein 1 plays a crucial role in the regulation of Sprouty4 in response
      to serum. 

PMID- 25957916
TI  - GroEL-GroES assisted folding of multiple recombinant proteins simultaneously over
      expressed in Escherichia coli.
AB  - Folding of aggregation prone recombinant proteins through co-expression of
      chaperonin GroEL and GroES has been a popular practice in the effort to optimize
      preparation of functional protein in Escherichia coli. Considering the demand for
      functional recombinant protein products, it is desirable to apply the chaperone
      assisted protein folding strategy for enhancing the yield of properly folded
      protein. Toward the same direction, it is also worth attempting folding of
      multiple recombinant proteins simultaneously over-expressed in E. coli through
      the assistance of co-expressed GroEL-ES. The genesis of this thinking was
      originated from the fact that cellular GroEL and GroES assist in the folding of
      several endogenous proteins expressed in the bacterial cell. Here we present the
      experimental findings from our study on co-expressed GroEL-GroES assisted folding
      of simultaneously over-expressed proteins maltodextrin glucosidase (MalZ) and
      yeast mitochondrial aconitase (mAco). Both proteins mentioned here are relatively
      larger and aggregation prone, mostly form inclusion bodies, and undergo GroEL-ES
      assisted folding in E. coli cells during over-expression. It has been reported
      that the relative yield of properly folded functional forms of MalZ and mAco with
      the exogenous GroEL-ES assistance were comparable with the results when these
      proteins were overexpressed alone. This observation is quite promising and
      highlights the fact that GroEL and GroES can assist in the folding of multiple
      substrate proteins simultaneously when over-expressed in E. coli. This method
      might be a potential tool for enhanced production of multiple functional
      recombinant proteins simultaneously in E. coli. 

PMID- 25957918
TI  - Nutritional state modulates growth hormone-stimulated lipolysis.
AB  - Growth hormone (GH) regulates several processes in vertebrates, including two
      metabolically disparate processes: promotion of growth, an anabolic action, and
      mobilization of stored lipid, a catabolic action. In this study, we used
      hepatocytes isolated from continuously fed and long-term (4weeks) fasted rainbow
      trout (Oncorhynchus mykiss) as a model to investigate the mechanistic basis of
      the anabolic and catabolic actions of GH. Our hypothesis was that nutritional
      state modulates the lipolytic responsiveness of cells by adjusting the signal
      transduction pathways to which GH links. GH stimulated lipolysis as measured by
      increased glycerol release in both a time- and concentration-related manner from
      cells of fasted fish but not from cells of fed fish. Expression of mRNAs that
      encode the lipolytic enzyme hormone-sensitive lipase (HSL), HSL1 and HSL2, also
      was stimulated by GH in cells from fasted fish and not in cells from fed fish.
      Activation of the signaling pathways that mediate GH action also was studied. In
      cells from fed fish, GH activated the JAK-STAT, PI3K-Akt, and ERK pathways,
      whereas in cells from fasted fish, GH activated the PLC/PKC and ERK pathways. In
      hepatocytes from fasted fish, blockade of PLC/PKC and of the ERK pathway
      inhibited GH-stimulated lipolysis and GH-stimulated HSL mRNA expression, whereas
      blockade of JAK-STAT or of the PI3K-Akt pathway had no effect on lipolysis or HSL
      expression stimulated by GH. These results indicate that during fasting GH
      activates the PLC/PKC and ERK pathways resulting in lipolysis but during periods
      of feeding GH activates a different complement of signal elements that do not
      promote lipolysis. These findings suggest that the responsiveness of cells to GH
      depends on the signal pathways to which GH links and helps resolve the growth
      promoting and lipid catabolic actions of GH. 

PMID- 25957917
TI  - Transfection of isolated rainbow trout, Oncorhynchus mykiss, granulosa cells
      through chemical transfection and electroporation at 12 degrees C.
AB  - Over-expression or inhibition of gene expression can be efficiently used to
      analyse the functions and/or regulation of target genes. Modulation of gene
      expression can be achieved through transfection of exogenous nucleic acids into
      target cells. Such techniques require the development of specific protocols to
      transfect cell cultures with nucleic acids. The aim of this study was to develop
      a method of transfection suitable for rainbow trout granulosa cells in primary
      culture. After the isolation of rainbow trout granulosa cells, chemical
      transfection of cells with a fluorescent morpholino oligonucleotide (MO) was
      tested using FuGENE HD at 12  degrees C. Electroporation was also employed to
      transfect these cells with either a plasmid or MO. Transfection was more
      efficient using electroporation (with the following settings: 1200 V/40 ms/1p)
      than chemical transfection, but electroporation by itself was deleterious,
      resulting in a decrease of the steroidogenic capacity of the cells, measured via
      estradiol production from its androgenic substrate. The disturbance of cell
      biology induced by the transfection method per se should be taken into account in
      data interpretation when investigating the effects of under- or over-expression
      of candidate genes.

PMID- 25957919
TI  - Human hospitalisations due to dog bites in Ireland (1998-2013): Implications for
      current breed specific legislation.
AB  - The aim of this study was to examine the efficacy of the current breed specific
      legislation in Ireland by investigating all dog bite hospital admissions
      throughout Ireland since that legislation was introduced. Data for statistical
      analyses were acquired through the National Hospital In-Patient Enquiry Scheme.
      In years 1998-2013, a total of 3164 human hospitalisations (admissions for dog
      bite) occurred in Ireland. Incidence of hospitalisations increased over this
      period (P <0.001). Male humans were at greater risk than females of dog bite
      hospitalisation (P = 0.015). Children under 10 years were identified as an at
      risk group. The present legislation is not effective as a dog bite mitigation
      strategy in Ireland and may be contributing to a rise in hospitalisations. 

PMID- 25957920
TI  - Effects of doxycycline on haematology, blood chemistry and peripheral blood
      lymphocyte subsets of healthy dogs and dogs naturally infected with Ehrlichia
      canis.
AB  - Canine monocytic ehrlichiosis (CME), caused by Ehrlichia canis, is a vector-borne
      disease with a worldwide distribution. It has been proposed that the
      pathogenesis, clinical severity and outcome of disease caused by Ehrlichia spp.
      can be attributed to the immune response rather than to any direct rickettsial
      effect. Moreover, doxycycline, the antimicrobial of choice for the treatment of
      CME, has immunomodulatory and anti-inflammatory properties associated with blood
      leukocyte proliferation function, cytokine synthesis, and matrix
      metalloproteinase activity. In order to assess the potential effects of
      doxycycline, dependent and independent of its antimicrobial activity, the present
      study compared changes in haematology, blood chemistry and circulating lymphocyte
      subpopulations in 12 healthy dogs and 20 dogs with CME after doxycycline therapy.
      Some changes were recorded only in the CME affected dogs, probably due to the
      antimicrobial effect of doxycycline. However, increases in mean corpuscular
      haemoglobin, mean corpuscular haemoglobin concentration, platelet count and
      alpha2-globulins, and decreased plasma creatinine were observed in both healthy
      and CME affected dogs. The absolute count of B lymphocytes (CD21(+)) increased
      initially, but then decreased until the end of the study period in both groups. A
      potential effect of doxycycline unrelated to its antimicrobial activity against
      E. canis is suggested, taking into account the results observed both in healthy
      dogs and in dogs with CME. 

PMID- 25957921
TI  - Infrared thermography of the udder after experimentally induced Escherichia coli
      mastitis in cows.
AB  - The study aimed to use infrared thermography (IRT) to evaluate the changes in
      udder surface temperature after induction of Escherichia coli mastitis in the
      right hind quarter. Over a time period of 24 h before to 24 h post-inoculation,
      thermograms of both hind quarters were taken every 2 h to determine maximum
      (Tmax) and average (Tavg) temperatures. Differences in both maximum and average
      temperatures (DTmax and DTavg) were calculated, as well as temperature
      differences between both hind quarters. All cows developed signs of clinical
      mastitis with a significant increase in DTmax and DTavg with Tmax at 13 h post
      inoculation for the (non-infected) left hind quarters. The results demonstrate
      that detection of mastitis using IRT is possible if the interval between
      examinations does not exceed 2 h. 

PMID- 25957922
TI  - Perspectives on the pathogenesis and treatment of canine monocytic ehrlichiosis
      (Ehrlichia canis).

PMID- 25957924
TI  - Urban/rural variation in the influence of widowhood on mortality risk: A cohort
      study of almost 300,000 couples.
AB  - Death of a spouse is associated with increased mortality risk for the surviving
      partner (the widowhood effect). We investigated whether the effect magnitude
      varied between urban, rural and intermediate areas, assembling death records
      (2001-2009) for a prospective cohort of 296,125 married couples in Northern
      Ireland. The effect was greatest during the first six months of widowhood in all
      areas and for both sexes. Subsequently, the effect was attenuated among men in
      rural and intermediate areas but persisted in urban areas (HRs and 95% CIs: rural
      1.09 [0.99, 1.21]; urban 1.35 [1.26, 1.44]). Among women the effect was
      attenuated in all areas (rural 1.06 [0.96, 1.17]; urban 1.09 [1.01, 1.17]). The
      impacts of spousal bereavement varied between urban and more rural areas,
      possibly due to variation in social support provided by the wider community. We
      identify men in urban areas as being in greatest need of such support and a
      possible target for health interventions. 

PMID- 25957925
TI  - "Nature is there; its free": Urban greenspace and the social determinants of
      health of immigrant families.
AB  - In this article, we draw on a 2012 Montreal-based study that examined the
      embodied, every day practices of immigrant children and families in the context
      of urban greenspaces such as parks, fields, backyards, streetscapes, gardens,
      forests and rivers. Results suggest that activities in the natural environment
      serve as a protective factor in the health and well-being of this population,
      providing emotional and physical nourishment in the face of adversity. Using the
      Social Determinants of Health model adopted by the World Health Organization
      (WHO, 1998), we analyze how participants accessed urban nature to minimize the
      effects of inadequate housing, to strengthen social cohesion and reduce emotional
      stress. We conclude with a discussion supporting the inclusion of the natural
      environment in the Social Determinants of Health Model. 

PMID- 25957923
TI  - Towards early inclusion of children in tuberculosis drugs trials: a consensus
      statement.
AB  - Children younger than 18 years account for a substantial proportion of patients
      with tuberculosis worldwide. Available treatments for paediatric drug-susceptible
      and drug-resistant tuberculosis, albeit generally effective, are hampered by high
      pill burden, long duration of treatment, coexistent toxic effects, and an overall
      scarcity of suitable child-friendly formulations. Several new drugs and regimens
      with promising activity against both drug-susceptible and drug-resistant strains
      have entered clinical development and are either in various phases of clinical
      investigation or have received marketing authorisation for adults; however, none
      have data on their use in children. This consensus statement, generated from an
      international panel of opinion leaders on childhood tuberculosis and
      incorporating reviews of published literature from January, 2004, to May, 2014,
      addressed four key questions: what drugs or regimens should be prioritised for
      clinical trials in children? Which populations of children are high priorities
      for study? When can phase 1 or 2 studies be initiated in children? What are the
      relevant elements of clinical trial design? The consensus panel found that
      children can be included in studies at the early phases of drug development and
      should be an integral part of the clinical development plan, rather than studied
      after regulatory approval in adults is obtained. 

PMID- 25957926
TI  - Novel biomarkers in cardiology: MicroRNAs in atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common sustained chronic cardiac arrhythmia
      in clinical practice, which increases the risk of stroke and thromboembolism and
      is an independent predictor of mortality. The underlying mechanisms involved in
      the development of AF have yet to be fully elucidated. However, once initiated,
      AF tends to self-perpetuate, owing to structural and electrical remodeling in the
      atria. MicroRNAs (miRNAs) represent a sizable sub-group of small non-coding RNAs,
      which degrades or inhibits the translation of their target mRNAs, thus regulating
      gene expression and playing an important role in a wide range of biologic
      processes. Clinically, there is increasing evidence of the potential diagnostic
      role of miRNAs as biomarkers, representing a novel therapeutic target in AF. The
      aim of this review is to provide an exhaustive overview of the role of miRNAs in
      AF and to discuss the diagnostic and therapeutic potential of miRNAs in this
      arrhythmia. 

PMID- 25957927
TI  - Clinical trials of N-acetylcysteine in psychiatry and neurology: A systematic
      review.
AB  - N-acetylcysteine (NAC) is recognized for its role in acetaminophen overdose and
      as a mucolytic. Over the past decade, there has been growing evidence for the use
      of NAC in treating psychiatric and neurological disorders, considering its role
      in attenuating pathophysiological processes associated with these disorders,
      including oxidative stress, apoptosis, mitochondrial dysfunction,
      neuroinflammation and glutamate and dopamine dysregulation. In this systematic
      review we find favorable evidence for the use of NAC in several psychiatric and
      neurological disorders, particularly autism, Alzheimer's disease, cocaine and
      cannabis addiction, bipolar disorder, depression, trichotillomania, nail biting,
      skin picking, obsessive-compulsive disorder, schizophrenia, drug-induced
      neuropathy and progressive myoclonic epilepsy. Disorders such as anxiety,
      attention deficit hyperactivity disorder and mild traumatic brain injury have
      preliminary evidence and require larger confirmatory studies while current
      evidence does not support the use of NAC in gambling, methamphetamine and
      nicotine addictions and amyotrophic lateral sclerosis. Overall, NAC treatment
      appears to be safe and tolerable. Further well designed, larger controlled trials
      are needed for specific psychiatric and neurological disorders where the evidence
      is favorable. 

PMID- 25957928
TI  - Should pharmacotherapy of digoxin be reviewed in male patients with heart failure
      in the case of association with carvedilol?

PMID- 25957929
TI  - Chronic alcoholic donors in heart transplantation: A mortality meta-analysis.

PMID- 25957930
TI  - Noninvasive vagus nerve stimulation: A novel feasible approach for
      cardioprotection during ischemia-reperfusion injury.

PMID- 25957931
TI  - Leriche-syndrome despite regular sport and non-compaction suggest neuromuscular
      disease.

PMID- 25957932
TI  - Prevalence of general and abdominal obesity among children and adolescents with
      different sitting height ratios in Shandong, China.

PMID- 25957933
TI  - Sleepiness, sleep, and use of sleepiness countermeasures in shift-working long
      haul truck drivers.
AB  - Driver sleepiness is a prevalent phenomenon among professional drivers working
      unconventional and irregular hours. For compromising occupational and traffic
      safety, sleepiness has become one of the major conundrums of road transportation.
      To further elucidate the phenomenon, an on-road study canvassing the under
      explored relationship between working hours and sleepiness, sleep, and use of
      sleepiness countermeasures during and outside statutory rest breaks was
      conducted. Testing the association between the outcomes and working hours,
      generalized estimating equations models were fitted on a data collected from 54
      long-haul truck drivers (mean 38.1 +/- 10.5 years, one female) volunteering in
      the 2-week study. Unobtrusive data-collection methods applied under naturalistic
      working and shift conditions included the Karolinska Sleepiness Scale (KSS)
      measuring sleepiness, a combination of actigraphy and sleep-log measuring sleep,
      and self-report questionnaire items incorporated into the sleep-log measuring the
      use of sleepiness countermeasures during and outside statutory rest breaks.
      Drivers' working hours were categorized into first and consecutive night, morning
      and day/evening shifts based on shift timing. The results reveal severe
      sleepiness (KSS>=7) was most prevalent on the first night (37.8%) and least on
      the morning (10.0%) shifts. Drivers slept reasonably well prior to duty hours,
      with main sleep being longest prior to the first night (total sleep time 7:21)
      and shortest prior to the morning (total sleep time 5:43) shifts. The proportion
      of shifts whereby drivers reported using at least one sleepiness countermeasure
      outside statutory rest breaks was approximately 22% units greater for the night
      than the non-night shifts. Compared to the day/evening shifts, the odds of severe
      sleepiness were greater only on the first night shifts (OR 6.4-9.1 with 95%
      confidence intervals, depending on the statistical model), the odds of
      insufficient daily sleep were higher especially prior to the consecutive night
      shifts (OR 3.5 with 95% confidence intervals), and the odds of using efficient
      sleepiness countermeasures outside statutory rest breaks were greater on the
      first as well as consecutive night shifts (OR 4.0-4.6 with 95% confidence
      intervals). No statistically significant association was found between shift type
      and use of efficient sleepiness countermeasures during statutory rest breaks. In
      all, the findings demonstrate marked differences in the occurrence of severe
      sleepiness at the wheel, sleep preceding duty hours, and the use of sleepiness
      countermeasures between different shift types. In addition, although drivers
      slept reasonably well in connection with different shift types, the findings
      imply there is still room for improvement in alertness management among this
      group of employees.

PMID- 25957934
TI  - Impact of alcohol checks and social norm on driving under the influence of
      alcohol (DUI).
AB  - This study investigated the influence of alcohol checks and social norm on self
      reported driving under the influence of alcohol above the legal limit (DUI). The
      analysis was based on the responses of 12,507 car drivers from 19 European
      countries to the SARTRE-4 survey (2010). The data were analysed by means of a
      multiple logistic regression-model on two levels: (1) individual and (2) national
      level. On the individual level the results revealed that driving under the
      influence (DUI) was positively associated with male gender, young age (17-34),
      personal experience with alcohol checks, the perceived likelihood of being
      checked for alcohol, perceived drunk driving behaviour of friends (social norm)
      and was negatively associated with higher age (55+). On a national level, the
      results showed a negative association with a lower legal alcohol limit (BAC
      0.2g/l compared with BAC 0.5g/l) and the percentage of drivers checked for
      alcohol. DUI was positively associated with the percentage of respondents in the
      country that reported that their friends drink and drive (social norm). The
      comparison of the results obtained on national and individual levels shows a
      paradoxical effect of alcohol checks: Countries with more alcohol checks show
      lower DUI (negative association) but respondents who have been personally checked
      for alcohol show a higher chance of DUI (positive association). Possible
      explanations of this paradox are discussed. The effects of the social norm
      variable (perceived drunk driving behaviour of friends) are positively associated
      with DUI on both levels. 

PMID- 25957935
TI  - Perimitral atrial tachycardia passing through a completely blocked mitral isthmus
      line?

PMID- 25957936
TI  - Layer modeling of zinc removal from metallic mixture of waste printed circuit
      boards by vacuum distillation.
AB  - A layer model was established to elucidate the mechanism of zinc removal from the
      metallic mixture of waste printed circuit boards by vacuum distillation. The
      removal process was optimized by response surface methodology, and the optimum
      operating conditions were the chamber pressure of 0.1Pa, heating temperature of
      923K, heating time of 60.0min, particle size of 70 mesh (0.212mm) and initial
      mass of 5.25g. Evaporation efficiency of zinc, the response variable, was 99.79%,
      which indicates that the zinc can be efficiently removed. Based on the
      experimental results, a mathematical model, which bears on layer structure,
      evaporation, mass transfer and condensation, interprets the mechanism of the
      variable effects. Especially, in order to reveal blocking effect on the zinc
      removal, the Blake-Kozeny-Burke-Plummer equation was introduced into the mass
      transfer process. The layer model can be applied to a wider range of metal
      removal by vacuum distillation. 

PMID- 25957937
TI  - A geological reconnaissance of electrical and electronic waste as a source for
      rare earth metals.
AB  - The mining of material resources requires knowledge about geogenic and
      anthropogenic deposits, in particular on the location of the deposits with the
      comparatively highest concentration of raw materials. In this study, we develop a
      framework that allows the establishment of analogies between geological and
      anthropogenic processes. These analogies were applied to three selected products
      containing rare earth elements (REE) in order to identify the most concentrated
      deposits in the anthropogenic cycle. The three identified anthropogenic deposits
      were characterised according to criteria such as "host rock", "REE
      mineralisation" and "age of mineralisation", i.e. regarding their "geological"
      setting. The results of this characterisation demonstrated that anthropogenic
      deposits have both a higher concentration of REE and a longer mine life than the
      evaluated geogenic deposit (Mount Weld, Australia). The results were further
      evaluated by comparison with the geological knowledge category of the United
      Nations Framework Classification for Fossil Energy and Mineral Reserves and
      Resources 2009 (UNFC-2009) to determine the confidence level in the deposit
      quantities. The application of our approach to the three selected cases shows a
      potential for recovery of REE in anthropogenic deposits; however, further
      exploration of both potential and limitations is required. 

PMID- 25957938
TI  - Rare earth elements and critical metal content of extracted landfilled material
      and potential recovery opportunities.
AB  - Rare earth elements (REEs), Platinum group metals (PGMs) and other critical
      metals currently attract significant interest due to the high risks of supply
      shortage and substantial impact on the economy. Their uses in many applications
      have made them present in municipal solid waste (MSW) and in commercial and
      industrial waste (C&I), since several industrial processes produce by-products
      with high content of these metals. With over 4000 landfills in the UK alone, the
      aim of this study was to assess the existence of these critical metals within
      landfills. Samples collected from four closed landfills in UK were subjected to a
      two-step acid digestion to extract 27 metals of interest. Concentrations across
      the four landfill sites were 58+/-6mgkg(-1) for REEs comprising 44+/-8mgkg(-1)
      for light REEs, 11+/-2mgkg(-1) for heavy REEs and 3+/-1mgkg(-1) for Scandium (Sc)
      and 3+/-1.0mgkg(-1) of PGMs. Compared to the typical concentration in ores, these
      concentrations are too low to achieve a commercially viable extraction. However,
      content of other highly valuable metals (Al and Cu) was found in concentrations
      equating to a combined value across the four landfills of around $400 million,
      which increases the economic viability of landfill mining. Presence of critical
      metals will mainly depend on the type of waste that was buried but the recovery
      of these metals through landfill mining is possible and is economically feasible
      only if additional materials (plastics, paper, metallic items and other) are also
      recovered for reprocessing. 

PMID- 25957939
TI  - Co-digestion of food waste in a municipal wastewater treatment plant: Comparison
      of batch tests and full-scale experiences.
AB  - The effects of co-digestion of food waste in a municipal wastewater treatment
      plant (WWTP) were studied in batch tests. The results obtained were compared with
      the mass balance of a digester at a full-scale WWTP for a one-year period without
      and with the addition of co-substrate. The specific methane yield calculated from
      the balance was 18% higher than the one in the batch tests, suggesting a
      stimulation of methane generation by co-digestion. It was hypothesized that this
      increase was caused by shifting the C/N ratio of raw sludge (8.8) to a more
      favourable ratio of the added food waste (17.7). In addition, potential benefits
      by adding food waste for energy autarky was investigated. While just 25% of the
      total energy demand of the plant could be recovered by biogas generation when no
      co-substrate was fed, this percentage has more than doubled when food waste was
      added at a ratio of 10% (w/w). 

PMID- 25957940
TI  - Augmentation of cognitive and behavioural therapies (CBT) with d-cycloserine for
      anxiety and related disorders.
AB  - BACKGROUND: A significant number of patients who suffer with anxiety and related
      disorders (that is post-traumatic stress disorder (PTSD), social anxiety disorder
      (SAnD), panic disorder with or without agoraphobia (PD), specific phobia (SPh)
      and obsessive compulsive disorder (OCD)) fail to respond optimally to first-line
      treatment with medication or cognitive and behavioural therapies. The addition of
      d-cycloserine (DCS) to cognitive and behavioural therapies may improve treatment
      response by impacting the glutamatergic system. This systematic review aimed to
      investigate the effects of adding DCS to cognitive and behavioural therapies by
      synthesising data from relevant randomised controlled trials and following the
      guidelines recommended by Cochrane. OBJECTIVES: To assess the effect of DCS
      augmentation of cognitive and behavioural therapies compared to placebo
      augmentation of cognitive and behavioural therapies in the treatment of anxiety
      and related disorders. Additionally, to assess the efficacy and tolerability of
      DCS across different anxiety and related disorders. SEARCH METHODS: This review
      fully incorporates studies identified from a search of the Cochrane Depression,
      Anxiety and Neurosis Controlled Trials Register (CCDANCTR) to 12 March 2015. This
      register includes relevant randomised controlled trials (RCTs) from: the Cochrane
      Library (all years), EMBASE (1974 to date), MEDLINE (1950 to date), PsycINFO
      (1967 to date), the World Health Organization's trials portal (ICTRP) and
      ClinicalTrials.gov . Reference lists from previous meta-analyses and reports of
      RCTs were also checked. No restrictions were placed on language, setting, date or
      publication status. SELECTION CRITERIA: All RCTs of DCS augmentation of cognitive
      and behavioural therapies versus placebo augmentation of cognitive and
      behavioural therapies for anxiety and related disorders were included. DATA
      COLLECTION AND ANALYSIS: Two authors (RO and TA) independently assessed RCTs for
      eligibility and inclusion, extracted outcomes and risk of bias data and entered
      these into a customised extraction form. Investigators were contacted to obtain
      missing data. In addition, data entry and analysis were performed by two review
      authors (KSW and HB). MAIN RESULTS: Twenty-one published RCTs, with 788
      participants in outpatient settings, were included in the review. Sixteen studies
      had an age range of 18 to 75 years, while four investigated paediatric
      populations aged 8 to 17 years and one included children, adolescents and adults.
      The 21 RCTs investigated OCD (number of RCTs (N) = 6), PTSD (N = 5), SAnD (N =
      5), SPh (N = 3) and PD (N = 2). Most information from the studies was rated as
      having either low risk or unclear risk of bias.There was no evidence of a
      difference between DCS augmentation of cognitive and behavioural therapies and
      placebo augmentation of cognitive and behavioural therapies for the treatment of
      anxiety and related disorders in adults at the endpoint (treatment responders, N
      = 9, risk ratio (RR) 1.10; 95% confidence interval (CI) 0.89 to 1.34; number of
      participants (n) = 449; low quality evidence) and between 1 and 12 months follow
      up (N = 7, RR 1.08; 95% CI 0.90 to 1.31; n = 383). DCS augmentation of cognitive
      and behavioural therapies was not superior to placebo augmentation of cognitive
      and behavioural therapies for children and adolescents, both at the endpoint (N =
      4, RR 1.01; 95% CI 0.78 to 1.31; n = 121; low quality evidence) and between 3 and
      12 months follow-up (N = 3, RR 0.86; 95% CI 0.67 to 1.09; n = 91).There was no
      evidence of a difference in treatment acceptability for DCS augmentation of
      cognitive and behavioural therapies compared with placebo augmentation of
      cognitive and behavioural therapies in adults (N = 16, RR 0.88; 95% CI 0.61 to
      1.25; n = 740), nor in children and adolescents (N = 4, RR 0.90; 95% CI 0.17 to
      4.69; n = 131). These conclusions were based on moderate quality evidence for
      adults, and very low quality evidence for children and adolescents. Although the
      observed difference was small, it is noteworthy that there was a high efficacy of
      exposure-based therapies alone in the included trials. Due to the limited number
      of studies, subgroup analysis of moderating factors for clinical and
      methodological effect could not take place. AUTHORS' CONCLUSIONS: This review
      found no evidence of a difference between DCS augmentation of cognitive and
      behavioural therapies and placebo augmentation of cognitive and behavioural
      therapies for treating anxiety and related disorders in children, adolescents and
      adults. These findings are based on low quality evidence from heterogenous
      studies with small sample sizes and incomplete data for clinical response, which
      precludes us from drawing conclusions on the use of DCS augmentation of cognitive
      and behavioural therapies at this stage. Given there is some promising
      preliminary data from individual studies, further research is necessary to assess
      DCS compared with placebo augmentation of cognitive and behavioural therapies,
      and determine mechanisms of action as well as magnitude of effect in anxiety and
      related disorders.

PMID- 25957941
TI  - Increasing the activity of immobilized enzymes with nanoparticle conjugation.
AB  - The efficiency and selectivity of enzymatic catalysis is useful to a plethora of
      industrial and manufacturing processes. Many of these processes require the
      immobilization of enzymes onto surfaces, which has traditionally reduced enzyme
      activity. However, recent research has shown that the integration of
      nanoparticles into enzyme carrier schemes has maintained or even enhanced
      immobilized enzyme performance. The nanoparticle size and surface chemistry as
      well as the orientation and density of immobilized enzymes all contribute to the
      enhanced performance of enzyme-nanoparticle conjugates. These improvements are
      noted in specific nanoparticles including those comprising carbon (e.g., graphene
      and carbon nanotubes), metal/metal oxides and polymeric nanomaterials, as well as
      semiconductor nanocrystals or quantum dots. 

PMID- 25957942
TI  - Frequent brief on-site simulation training and reduction in 24-h neonatal
      mortality--an educational intervention study.
AB  - AIM OF THE STUDY: "Helping Babies Breathe" (HBB) is a simulation-based
      educational program developed to help reduce perinatal mortality worldwide. A one
      day HBB training course did not improve clinical management of neonates. The
      objective was to assess the impact of frequent brief (3-5 min weekly) on-site HBB
      simulation training on newborn resuscitation practices in the delivery room and
      the potential impact on 24-h neonatal mortality. METHODS: Before/after
      educational intervention study in a rural referral hospital in Northern Tanzania.
      Baseline data was collected from 01.02.2010 to 31.01.2011 and post-intervention
      data from 01.02.2011 to 31.01.2012. All deliveries were observed by research
      assistants who recorded information about labor, newborn delivery room
      management, perinatal characteristics, and neonatal outcomes. A newborn simulator
      was placed in the labor ward and frequent brief HBB simulation training was
      implemented on-site; 3-min of weekly paired practice, assisted by local-trainers.
      Local-trainers also facilitated 40-min monthly re-trainings. Outcome measures
      were; delivery room management of newborns and 24-h neonatal outcomes (normal,
      admitted to a neonatal area, death, or stillbirths). RESULTS: There were 4894
      deliveries pre and 4814 post-implementation of frequent brief simulation
      training. The number of stimulated neonates increased from 712(14.5%) to
      785(16.3%) (p = 0.016), those suctioned increased from 634(13.0%) to 762(15.8%)
      (p <= 0.0005). Neonates receiving bag mask ventilation decreased from 357(7.3%)
      to 283(5.9%) (p = 0.005). Mortality at 24-h decreased from 11.1/1000 to 7.2/1000
      (p = 0.040). CONCLUSION: On-site, brief and frequent HBB simulation training
      appears to facilitate transfer of new knowledge and skills into clinical practice
      and to be accompanied by a decrease in neonatal mortality.

PMID- 25957943
TI  - Public knowledge of automatic external defibrillators in a large U.S. urban
      community.
AB  - BACKGROUND: Sudden cardiac arrest (SCA) strikes over 40,000 people in the public
      environment annually in the U.S., but despite evidence-based interventions such
      as prompt CPR and defibrillation, less than 25% of patients survive public SCA
      events. Effective use of automated external defibrillators (AEDs), especially by
      lay bystanders, represents an important strategy to improve survival rates.
      Previous investigations in Europe and Asia have demonstrated variable public
      awareness of AEDs; layperson knowledge of AEDs in the U.S. is poorly
      characterized. OBJECTIVE: To measure understanding of AEDs among the general
      public, at multiple sites within a busy urban transportation system. METHODS:
      Surveys were administered at two high-volume train stations in Philadelphia,
      Pennsylvania between April and June, 2013. RESULTS: A total of 514 surveys were
      completed. Two thirds (66%) of respondents were able to correctly identify an AED
      and its purpose, and just over half (58%) of respondents reported willingness to
      use an AED in an emergency situation. Less than 10% of respondents presented with
      a hypothetical SCA scenario spontaneously mentioned using an AED when asked what
      actions they would take. CONCLUSIONS: In this cross-sectional survey, public
      knowledge about AEDs and their use was high; however, a smaller number of
      respondents expressed thoughts of using the device in an emergency situation and
      demonstrated willingness to serve as a responder. Increased education and
      training efforts, as well as potential interventions such as 911 dispatcher
      assisted AED use may help improve bystander response in SCA events.

PMID- 25957944
TI  - Psychological impact on dispatched local lay rescuers performing bystander
      cardiopulmonary resuscitation.
AB  - AIM: We studied the short-term psychological impact and post-traumatic stress
      disorder (PTSD)-related symptoms in lay rescuers performing cardiopulmonary
      resuscitation (CPR) after a text message (TM)-alert for out-of-hospital-cardiac
      arrest, and assessed which factors contribute to a higher level of PTSD-related
      symptoms. METHODS: The lay rescuers received a TM-alert and simultaneously an
      email with a link to an online questionnaire. We analyzed all questionnaires from
      February 2013 until October 2014 measuring the short-term psychological impact.
      We interviewed by telephone all first arriving lay rescuers performing bystander
      CPR and assessed PTSD-related symptoms with the Impact of Event Scale (IES) 4-6
      weeks after the resuscitation. IES-scores 0-8 reflected no stress, 9-25 mild, 26
      43 moderate, and 44-75 severe stress. A score >= 26 indicated PTSD
      symptomatology. RESULTS: Of all alerted lay rescuers, 6572 completed the online
      questionnaire. Of these, 1955 responded to the alert and 507 assisted in the
      resuscitation. We interviewed 203 first arriving rescuers of whom 189 completed
      the IES. Of these, 41% perceived no/mild short-term impact, 46% bearable impact
      and 13% severe impact. On the IES, 81% scored no stress and 19% scored mild
      stress. None scored moderate or severe stress. Using a multivariable logistic
      regression model we identified three factors with an independent impact on mild
      stress level: no automated external defibrillator connected by the lay rescuer,
      severe short-term impact, and no (very) positive experience. CONCLUSION: Lay
      rescuers alerted by text messages, do not show PTSD-related symptoms 4-6 weeks
      after performing bystander CPR, even if they perceive severe short-term
      psychological impact.

PMID- 25957945
TI  - A matter of identity - Phenotype and differentiation potential of human somatic
      stem cells.
AB  - Human somatic stem cells with neural differentiation potential can be valuable
      for developing cell-based therapies, including treatment of birth-related
      defects, while avoiding issues associated with cell reprogramming. Precisely
      defining the "identity" and differentiation potential of somatic stem cells from
      different sources, has proven difficult, given differences in sets of specific
      markers, protocols used and lack of side-by-side characterization of these cells
      in different studies. Therefore, we set to compare expression of mesenchymal and
      neural markers in human umbilical cord-derived mesenchymal stem cells (UC-MSCs),
      pediatric adipose-derived stem cells (p-ADSCs) in parallel with human neural stem
      cells (NSCs). We show that UC-MSCs at a basal level express mesenchymal and so
      called "neural" markers, similar to that we previously reported for the p-ADSCs.
      All somatic stem cell populations studied, independently from tissue and patient
      of origin, displayed a remarkably similar expression of surface markers, with the
      main difference being the restricted expression of CD133 and CD34 to NSCs.
      Expression of certain surface and neural markers was affected by the expansion
      medium used. As predicted, UC-MSCs and p-ADSCs demonstrated tri-mesenchymal
      lineage differentiation potential, though p-ADSCs display superior chondrogenic
      differentiation capability. UC-MSCs and p-ADSCs responded also to neurogenic
      induction by up-regulating neuronal markers, but crucially they appeared
      morphologically immature when compared with differentiated NSCs. This highlights
      the need for further investigation into the use of these cells for neural
      therapies. Crucially, this study demonstrates the lack of simple means to
      distinguish between different cell types and the effect of culture conditions on
      their phenotype, and indicates that a more extensive set of markers should be
      used for somatic stem cell characterization, especially when developing
      therapeutic approaches. 

PMID- 25957947
TI  - The fibrillin microfibril scaffold: A niche for growth factors and
      mechanosensation?
AB  - The fibrillins, large extracellular matrix molecules, are polymerized to form
      "microfibrils." The fibrillin microfibril scaffold is populated by microfibril
      associated proteins and by growth factors, which are likely to be latent. The
      scaffold, associated proteins, and bound growth factors, together with cellular
      receptors that can sense the microfibril matrix, constitute the fibrillin
      microenvironment. Activation of TGFbeta signaling is associated with the Marfan
      syndrome, which is caused by mutations in fibrillin-1. Today we know that
      mutations in fibrillin-1 cause the Marfan syndrome as well as Weill-Marchesani
      syndrome (and other acromelic dysplasias) and result in opposite clinical
      phenotypes: tall or short stature; arachnodactyly or brachydactyly; joint
      hypermobility or stiff joints; hypomuscularity or hypermuscularity. We also know
      that these different syndromes are associated with different structural
      abnormalities in the fibrillin microfibril scaffold and perhaps with specific
      cellular receptors (mechanosensors). How does the microenvironment, framed by the
      microfibril scaffold and populated by latent growth factors, work? We must await
      future investigations for the molecular and cellular mechanisms that will answer
      this question. However, today we can appreciate the importance of the fibrillin
      microfibril niche as a contextual environment for growth factor signaling and
      potentially for mechanosensation. 

PMID- 25957946
TI  - Chemoattraction of bone marrow-derived stem cells towards human endometrial
      stromal cells is mediated by estradiol regulated CXCL12 and CXCR4 expression.
AB  - Bone marrow derived cells engraft to the uterine endometrium and contribute to
      endometriosis. The mechanism by which these cells are mobilized and directed to
      the endometrium has not been previously characterized. We demonstrate that human
      endometrial stromal cells (hESCs) produce the chemokine CXCL12 and that bone
      marrow cells (BMCs) express the CXCL12 receptor, CXCR4. Treatment with
      physiological levels of estradiol (E2) induced both CXCL12 and CXCR4 expression
      in hESCs and BMCs, respectively. BMCs migrated towards hESCs conditioned media; a
      CXCR4 antagonist blocked migration indicating that CXCL12 acting through its
      receptor, CXCR4, is necessary for chemoattraction of BM cells to human
      endometrial cells. E2 increased both CXCL12 expression in endometrial cells and
      CXCR4 expression in BM cells, further enhancing chemoattraction. E2 induced
      CXCL12/CXCR4 expression in endometrium and BM, respectively, drives migration of
      stem cells to the endometrium. The E2-CXCL12/CXCR4 signaling pathway may be
      useful in determining treatments for endometrial disorders, and may be
      antagonized to block stem cell migration to endometriosis. 

PMID- 25957948
TI  - Introduction to the mini-review series "Extracellular determinants of cell
      signaling".

PMID- 25957950
TI  - The Confidence Information Ontology: a step towards a standard for asserting
      confidence in annotations.
AB  - Biocuration has become a cornerstone for analyses in biology, and to meet needs,
      the amount of annotations has considerably grown in recent years. However, the
      reliability of these annotations varies; it has thus become necessary to be able
      to assess the confidence in annotations. Although several resources already
      provide confidence information about the annotations that they produce, a
      standard way of providing such information has yet to be defined. This lack of
      standardization undermines the propagation of knowledge across resources, as well
      as the credibility of results from high-throughput analyses. Seeded at a workshop
      during the Biocuration 2012 conference, a working group has been created to
      address this problem. We present here the elements that were identified as
      essential for assessing confidence in annotations, as well as a draft ontology-
      the Confidence Information Ontology--to illustrate how the problems identified
      could be addressed. We hope that this effort will provide a home for discussing
      this major issue among the biocuration community. Tracker URL:
      https://github.com/BgeeDB/confidence-information-ontology Ontology URL:
      https://raw.githubusercontent.com/BgeeDB/confidence-information
      ontology/master/src/ontology/cio-simple.obo

PMID- 25957949
TI  - ADAMTS proteins as modulators of microfibril formation and function.
AB  - The ADAMTS (a disintegrin-like and metalloproteinase domain with thrombospondin
      type 1 motifs) protein superfamily includes 19 secreted metalloproteases and 7
      secreted ADAMTS-like (ADAMTSL) glycoproteins. The possibility of functional
      linkage between ADAMTS proteins and fibrillin microfibrils was first revealed by
      a human genetic consilience, in which mutations in ADAMTS10, ADAMTS17, ADAMTSL2
      and ADAMTSL4 were found to phenocopy rare genetic disorders caused by mutations
      affecting fibrillin-1 (FBN1), the major microfibril component in adults. The
      manifestations of these ADAMTS gene disorders in humans and animals suggested
      that they participated in the structural and regulatory roles of microfibrils.
      Whereas two such disorders, Weill-Marchesani syndrome 1 and Weill-Marchesani-like
      syndrome involve proteases (ADAMTS10 and ADAMTS17, respectively), geleophysic
      dysplasia and isolated ectopia lentis in humans involve ADAMTSL2 and ADAMTSL4,
      respectively, which are not proteases. In addition to broadly similar
      dysmorphology, individuals affected by Weill-Marchesani syndrome 1, Weill
      Marchesani-like syndrome or geleophysic dysplasia each show characteristic
      anomalies suggesting molecule-, tissue-, or context-specific functions for the
      respective ADAMTS proteins. Ectopia lentis occurs in each of these conditions
      except geleophysic dysplasia, and is due to a defect in the ciliary zonule, which
      is predominantly composed of FBN1 microfibrils. Together, this strongly suggests
      that ADAMTS proteins are involved either in microfibril assembly, stability, and
      anchorage, or the formation of function-specific supramolecular networks having
      microfibrils as their foundation. Here, the genetics and molecular biology of
      this subset of ADAMTS proteins is discussed from the perspective of how they
      might contribute to fully functional or function-specific microfibrils. 

PMID- 25957951
TI  - Coping with breast cancer and relapse: Stability of coping and long-term outcomes
      in an observational study over 10 years.
AB  - Many studies dealing with relationships between coping and breast cancer were
      based on a single measurement of coping behaviour. Assessments were taking place
      soon after surgery of primary breast cancer, and effects on long-term outcomes
      were considered. In our study it was examined whether coping behaviours are
      stable over time and whether they were associated with breast cancer recurrence.
      The analyses were based on a long-term study with initially 254 patients with
      three interviews and an outcome assessment within a total study period of 10
      years. Data were collected by means of qualitative interviews and standardized
      questionnaires. Ways of coping in terms of helplessness, denial, mastery, and
      hope/optimism were classified by interviewer-based ratings within the framework
      of a standardized rating procedure. The reliability of rating standards was
      assured by continuous training and by estimating inter-rater agreements. Outcome
      measures were drawn from registries and patients' files. Coping behaviours over
      three interviews within six years after surgery turned out to be highly variable,
      and the respective correlations were low. For none of the four ways of coping
      associations with recurrence emerged. Coping in response to breast cancer was not
      stable over time, so we may conclude that the results of one measurement assessed
      early in the disease course should not be considered as constant over longer time
      periods. Coping behaviours were unrelated with recurrence, a finding that might
      be relieving from a patient perspective. 

PMID- 25957953
TI  - Behavioural responses of Eastern grey squirrels, Sciurus carolinensis, to cues of
      risk while foraging.
AB  - Previous studies have shown that Eastern grey squirrels modify their behaviour
      while foraging to offset risks of social and predatory costs, but none have
      simultaneously compared whether such modifications are performed at a cost to
      foraging. The present study directly compares how grey squirrels respond to cues
      of these risks while foraging. We simulated social risk and predatory risk using
      acoustic playbacks of stimuli that grey squirrels might be exposed to at a
      foraging patch: calls of conspecifics, heterospecifics (competitor and non
      competitor) and predators. We found that grey squirrels responded to predator,
      heterospecific competitor and conspecific playbacks by altering their foraging
      and vigilance behaviours. Foraging was most disrupted by increased vigilance when
      we played calls of predators. Squirrels' response to calls of heterospecific
      competitors did not differ from their response to conspecific calls, and they
      resumed foraging more quickly after both compared to predator calls: whereas they
      showed little response to calls of non-competitor heterospecifics and a white
      noise control. We conclude that squirrels respond differentially to calls made by
      conspecifics, heterospecific competitors and predators, with the most pronounced
      response being to calls of predators. We suggest that squirrels may view
      conspecific and corvid vocalisations as cues of potential conflict while
      foraging, necessitating increased vigilance. 

PMID- 25957952
TI  - A hydrophobic proline-rich motif is involved in the intracellular targeting of
      temperature-induced lipocalin.
AB  - Temperature-induced lipocalins (TILs) play an essential role in the response of
      plants to different abiotic stresses. In agreement with their proposed role in
      protecting membrane lipids, TILs have been reported to be associated to cell
      membranes. However, TILs show an overall hydrophilic character and do not contain
      any signal for membrane targeting nor hydrophobic sequences that could represent
      transmembrane domains. Arabidopsis TIL (AtTIL) is considered the ortholog of
      human ApoD, a protein known to associate to membranes through a short hydrophobic
      loop protruding from strands 5 and 6 of the lipocalin beta-barrel. An equivalent
      loop (referred to as HPR motif) is also present between beta-strands 5 and 6 of
      TILs. The HPR motif, which is highly conserved among TIL proteins, extends over
      as short stretch of eight amino acids and contains four invariant proline
      residues. Subcellular localization studies have shown that TILs are targeted to a
      variety of cell membranes and organelles. We have also found that the HPR motif
      is necessary and sufficient for the intracellular targeting of TILs. Modeling
      studies suggest that the HPR motif may directly anchor TILs to cell membranes,
      favoring in this way further contact with the polar group of membrane lipids.
      However, some particular features of the HPR motif open the possibility that
      targeting of TILs to cell membranes could be mediated by interaction with other
      proteins. The functional analysis of the HPR motif unveils the existence of novel
      mechanisms involved in the intracellular targeting of proteins in plants. 

PMID- 25957954
TI  - Marble-burying is enhanced in 3xTg-AD mice, can be reversed by risperidone and it
      is modulable by handling.
AB  - Translational research on behavioural and psychological symptoms of dementia
      (BPSD) is relevant to the study the neuropsychiatric symptoms that strongly
      affect the quality of life of the human Alzheimer's disease (AD) patient and
      caregivers, frequently leading to early institutionalization. Among the
      ethological behavioural tests for rodents, marble burying is considered to model
      the spectrum of anxiety, psychotic and obsessive-compulsive like symptoms. The
      present work was aimed to study the behavioural interactions of 12 month-old male
      3xTg-AD mice with small objects using the marble-burying test, as compared to the
      response elicited in age-matched non-transgenic (NTg) mice. The distinction of
      the classical 'number of buried marbles' but also those left 'intact' and those
      'changed' of position of marbles or partially buried (the transitional level of
      interaction) provided new insights into the modelling of BPSD-like alterations in
      this AD model. The analysis revealed genotype differences in the behavioural
      patterns and predominant behaviors. In the NTg mice, predominance was shown in
      the 'changed or partially buried', while interactions with marble were enhanced
      in 3xTg-AD mice resulting in an increase of marble burying. Besides, genotype
      dependent meaningful correlations were found, with the marble test pattern of
      3xTg-AD mice being directly related to neophobia in the corner tests. In both
      genotypes, the increase of burying was reversed by chronic treatment with
      risperidone (1mg/kg, s.c.). In 3xTg-AD mice, the repetitive handling of animals
      during the treatment also exerted modulatory effects. These distinct patterns
      further characterize the modelling of BPSD-like symptoms in the 3xTg-AD mice, and
      provide another behavioural tool to assess the benefits of preventive and/or
      therapeutic strategies, as well as the potential action of risk factors for AD,
      in this animal model. 

PMID- 25957955
TI  - [Aquagenic palmoplantar keratodermas].

PMID- 25957957
TI  - Influence of metastatic disease on the usefulness of uracil pharmacokinetics as a
      screening tool for DPD activity in colorectal cancer patients.
AB  - PURPOSE: Dihydropyrimidine dehydrogenase (DPD) deficiency can lead to severe
      toxicity in patients treated with a standard dose of a fluoropyrimidine such as 5
      fluorouracil or capecitabine (CAP). Administration of oral uracil and subsequent
      measurement of uracil and dihydrouracil (DHU) plasma concentrations has been used
      to identify patients with DPD deficiency. Liver metastasis might influence
      systemic DPD activity. The aim of the study was to investigate the effect of
      metastatic disease on the pharmacokinetics of uracil and DHU after oral
      administration of uracil. METHODS: 500 mg/m(2) uracil was administered orally to
      12 subjects with stages II-III colorectal cancer (CRC) who were treated in the
      adjuvant setting and to 12 subjects with stage IV metastasized CRC, all treated
      with CAP containing therapy. All subjects had a normal DPD activity defined as >6
      nmol/mg/h determined in peripheral blood mononuclear cells. RESULTS: The mean
      uracil clearance [CL 51.7 (SD 6.4) vs. 46.7 (SD 13.0) l/h], area under the curve
      [AUC0-220min 20.6 (SD 6.4) vs. 21.0 (SD 5.7) h mg/l], elimination half-life [t
      1/2 21 (SD 7) vs. 21 (SD 8) min], maximum concentration time [T max 27 (SD 9) vs.
      25 (SD 9) min], volume of distribution [V 26.58 (SD 10.11) vs. 21.10 (SD 8.48) l]
      and the elimination constant [k el 2.01 (SD 0.56) vs. 2.41 (SD 0.72) h(-1)] did
      not differ significantly (p > 0.05) non-metastatic CRD versus metastatic CRC.
      CONCLUSIONS: Metastasis does not alter uracil pharmacokinetics and is similar in
      CRC patients with and without metastasis. Therefore, the uracil test dose could
      be used as a DPD phenotype test in both adjuvantly treated and metastatic CRC
      patients using similar cutoff criteria to identify patients with DPD deficiency.

PMID- 25957958
TI  - Extension of the Calvert formula to patients with severe renal insufficiency.
AB  - PURPOSE: The Calvert formula was derived from the study among patients with
      glomerular filtration rates (GFRs) of 33-135 ml/min, and it remains unclear
      whether the formula can be used to calculate optimal and safe dosages of
      carboplatin in patients with severe renal insufficiency. We evaluated the utility
      of this formula in patients with severe renal insufficiency. METHODS: For
      pharmacokinetic analysis, we studied nine adult Japanese patients with advanced
      cancer who had an estimated GFR of lower than 30 ml/min/1.73 m(2), as calculated
      by the Japanese equation for estimating GFR, or who were receiving hemodialysis.
      The dose of carboplatin was calculated with the Calvert formula, in which GFR was
      measured by inulin clearance or was assumed to be 0 in patients requiring
      hemodialysis. Hemodialysis was started 23 h after the end of carboplatin
      infusion. RESULTS: Although there was a significant correlation between the
      estimated and measured carboplatin clearance, the estimated clearance was
      consistently higher than the measured clearance [mean prediction error +/-
      standard deviation = 41.0 +/- 26.3 %] in all seven patients with renal
      insufficiency (GFR, median 21.4, range 7.8-31.4 ml/min) and in the two
      hemodialysis patients. Actual areas under the concentration-time curve (AUC)
      (mg/ml min) were 5.4, 5.7, 6.2, and 9.0 for the four patients with a target AUC
      (mg/ml min) of 5; 5.7, 6.2, and 7.1 for the three patients with a target AUC
      (mg/ml min) of 4; and 5.1 and 8.7 for the two hemodialysis patients with a target
      AUC (mg/ml min) of 5. The measured clearance of carboplatin ranged from 23.0 to
      51.3 ml/min in the seven patients not receiving hemodialysis. The pre
      hemodialysis carboplatin clearance in the hemodialysis patients was 20.5 and 11.1
      ml/min, respectively. CONCLUSION: For adult patients with severe renal
      insufficiency, the Calvert formula causes carboplatin overdosing by
      overestimating the carboplatin clearance.

PMID- 25957959
TI  - Editorial: New Frontiers in East Asian Psycholinguistics.

PMID- 25957956
TI  - T Cells-Protective or Pathogenic in Alzheimer's Disease?
AB  - Alzheimer's disease (AD) is the most common cause of dementia, and is
      characterised by deposits of amyloid beta (Abeta), neurofibrillary tangles and
      neuronal loss. Neuroinflammatory changes have been identified as a feature of the
      disease, and recent studies have suggested a potential role for the peripheral
      immune system in driving these changes and, ultimately, the associated neuronal
      degeneration. A number of reports have detailed changes in the activation state
      and subtype of T cells in the circulation and CSF of AD patients and there is
      evidence of T cell infiltration into the brain. In this review, we examine the
      possible impact of T cell infiltration in the progression of pathology in AD and
      consider the data obtained from animal models of the disease. We consider how
      these cells infiltrate the brain, particularly in AD, and discuss whether the
      presence of T cells in the AD brain is protective or pathogenic. Finally we
      evaluate the current therapies, particularly those that involve immunization. 

PMID- 25957960
TI  - The prognostic value of cerebrospinal fluid characteristics in dogs without deep
      pain perception due to thoracolumbar disc herniation.
AB  - Providing a pre-operative prognosis for dogs presented with absent deep pain
      perception (DPP) is extremely challenging, as the overall recovery rates widely
      vary. This study assesses the possible correlation between the severity of spinal
      cord injury and CSF cytology in 31 paraplegic dogs presented with absent DPP due
      to acute thoracolumbar intervertebral disc herniation (TL-IVDH). All dogs
      underwent surgical decompression immediately following diagnosis. CSF TNCC,
      macrophage percentage and macrophage to monocyte (MPhi:M) ratio were
      significantly higher in dogs that failed to regain DPP within 10 days post
      operatively and in dogs that failed to regain ambulation at the end of the study
      period (P< 0.05). MPhi:M of 0.73 and higher corresponded to a sensitivity of 54%
      and specificity of 100% for prediction of a negative long-term outcome. CSF TNCC,
      macrophage percentage and MPhi:M ratio effectively predicted regaining DPP and
      the long-term outcome in dogs that lost DPP due to acute TL-IVDH. 

PMID- 25957961
TI  - High-resolution Crystal Structure of Dimeric VP40 From Sudan ebolavirus.
AB  - Ebolaviruses cause severe hemorrhagic fever. Central to the Ebola life cycle is
      the matrix protein VP40, which oligomerizes and drives viral budding. Here we
      present the crystal structure of the Sudan virus (SUDV) matrix protein. This
      structure is higher resolution (1.6 A) than previously achievable. Despite
      differences in the protein purification, we find that it still forms a stable
      dimer in solution, as was noted for other Ebola VP40s. Although the N-terminal
      domain interface by which VP40 dimerizes is conserved between Ebola virus and
      SUDV, the C-terminal domain interface by which VP40 dimers may further assemble
      is significantly smaller in this SUDV assembly. 

PMID- 25957963
TI  - Adenovirus-Vectored Vaccine Provides Postexposure Protection to Ebola Virus
      Infected Nonhuman Primates.
AB  - Ebola virus (EBOV) causes lethal disease in up to 90% of EBOV-infected humans.
      Among vaccines, only the vesicular stomatitis virus platform has been successful
      in providing postexposure protection in nonhuman primates. Here, we show that an
      adjuvanted human adenovirus serotype 5 (Ad5)-vectored vaccine (Ad5-Zaire EBOV
      glycoprotein) protected 67% (6 of 9) and 25% (1 of 4) of cynomolgus macaques when
      administered 30 minutes and 24 hours following EBOV challenge, respectively. The
      treatment also protected 33% of rhesus macaques (1 of 3) when given at 24 hours.
      The results highlight the utility of adjuvanted Ad5 vaccines for rapid
      immunization against EBOV. 

PMID- 25957962
TI  - State-of-the-Art Workshops on Medical Countermeasures Potentially Available for
      Human Use Following Accidental Exposures to Ebola Virus.
AB  - The ongoing outbreak of Ebola in West Africa has raised a general awareness that
      at present there are no Ebola-specific medical countermeasures (MCMs) with proven
      effectiveness. This paper recapitulates discussions held at the 6th International
      Filovirus Symposium in March 2014 as well as the subsequent design of a
      randomized clinical trial design for treating Ebola virus-infected patients
      evacuated from West Africa to the United States. A number of different drugs or
      biologics were critically reviewed and 3 different postexposure strategies were
      identified as being farthest along in development; passive immunotherapy with
      monoclonal antibodies, postexposure vaccination with constructs involving viral
      vectors (such as vesicular stomatitis virus), and antisense compounds directly
      targeting the viral genome such as modified phosphorodiamidate morpholino
      oligomer-based compounds and small interfering RNA products. At the time of the
      meetings, there were no investigational new drugs (INDs) in place for the
      candidate MCMs. Developers and sponsors of these candidate products were strongly
      encouraged to prepare pre-IND packets and submit pre-IND meeting requests to the
      Food and Drug Administration. Some of these investigational products have already
      been used under emergency authorizations to treat patients in Africa as well as
      patients evacuated to the United States or Western Europe. 

PMID- 25957964
TI  - A Single-Vector, Single-Injection Trivalent Filovirus Vaccine: Proof of Concept
      Study in Outbred Guinea Pigs.
AB  - The filoviruses, Marburg marburgvirus (MARV), Zaire ebolavirus (ZEBOV), and Sudan
      ebolavirus (SEBOV), cause severe and often fatal hemorrhagic fever in humans and
      nonhuman primates (NHPs). Monovalent recombinant vesicular stomatitis virus
      (rVSV)-based vaccine vectors, which encode a filovirus glycoprotein (GP) in place
      of the VSV glycoprotein, have shown 100% efficacy against homologous filovirus
      challenge in rodent and NHP studies. Here, we examined the utility of a single
      vector, single-injection trivalent rVSV vector expressing MARV, ZEBOV, and SEBOV
      GPs to protect against MARV-, ZEBOV-, and SEBOV-induced disease in outbred
      Hartley guinea pigs where we observed protection from effects of all 3
      filoviruses. 

PMID- 25957965
TI  - Soluble Glycoprotein Is Not Required for Ebola Virus Virulence in Guinea Pigs.
AB  - Ebola virus (EBOV) uses transcriptional editing to express several glycoproteins
      (GPs), including secreted soluble GP (sGP) and structural GP1,2, from a single
      gene. Recombinant viruses predominantly expressing GP1,2 are known to rapidly
      mutate and acquire an editing site predominantly expressing sGP in vivo,
      suggesting an important role of this protein during infection. Therefore, we
      generated a recombinant virus that is no longer able to express sGP and assessed
      its virulence in the EBOV guinea pig model. Surprisingly, although this virus
      remained genetically stable, it did not show any significant attenuation in vivo,
      showing that sGP is not required for virulence in this model. 

PMID- 25957966
TI  - Immune Response to Marburg Virus Angola Infection in Nonhuman Primates.
AB  - BACKGROUND: The 2005 outbreak of Marburg virus (MARV) infection in Angola was the
      most lethal MARV infection outbreak in history, with a case-fatality rate (90%)
      similar to that for Zaire ebolavirus (EBOV) infection. However, very little is
      known about the pathogenicity of MARV Angola, as few studies have been conducted
      to date. Therefore, the immune response was examined in MARV Angola-infected
      nonhuman primates. METHODS: Cynomolgus macaques were infected with MARV Angola
      and monitored for survival. The effect of MARV Angola on the immune system was
      examined by immunophenotyping whole-blood and by analyzing cytokine and chemokine
      levels in plasma and spleen specimens, using flow cytometry. RESULTS: The
      prominent clinical findings were rapid onset of disease and death (mean time
      after infection, 6.7 days), fever, depression, anorexia, petechial rash, and
      lymphopenia. Specifically, T, B, and natural killer cells were severely depleted
      in the blood by day 6. The typical cytokine storm was present, with levels of
      interferon gamma, tumor necrosis factor, interleukin 6, and CCL2 rising in the
      blood early during infection. CONCLUSIONS: MARV Angola displayed the same
      virulence and disease pathology as EBOV. MARV Angola appears to cause a more
      rapid onset and severe outcome of infection than other MARV strains.

PMID- 25957967
TI  - Simple enucleation for the treatment of highly complex renal tumors:
      Perioperative, functional and oncological results.
AB  - AIM: To assess the role of simple enucleation (SE) for the treatment of highly
      complex renal tumors. METHODS: Overall, 96 Preoperative Aspects and Dimensions
      Used for an Anatomical (PADUA) classification score 10 to 13 renal tumors were
      treated with SE at our institution. All conventional perioperative variables,
      surgical, functional and oncological results were gathered in a prospectively
      maintained database. Survival curves were generated using a Kaplan-Meier method.
      Univariate analysis assessed the outcome differences. RESULTS: Mean (+/- 1s.d.)
      clinical tumor diameter was 4.8 (+/- 1.6 cm). 70.8% of patients had >= cT1b
      stage. The PADUA score was recorded as 10, 11, 12 and 13 in 57.3%, 29.2%, 11.5%,
      and 2.1% of tumors respectively. Overall, 76 patients were treated with an open
      approach and 20 robotically. Mean warm ischemia time (WIT) was 19.2 min, and WIT
      greater than 25 min occurred in 14.6% of cases. Positive surgical margin (PSM)
      rate was 3.6% and trifecta was achieved in 64.3% of patients. Postoperative
      surgical complications occurred in 24% of patients, with 14.6% Clavien-Dindo
      grade 1-2, 8.3% grade 3, and 1% grade 4. Five-year cancer specific survival
      (CSS), recurrent free survival (RFS), and overall survival (OS) rates resulted
      96.1%, 90.8% and 88.0%, respectively. Overall, 4.2% of patients experienced
      progressive disease. At follow-up, the mean decrease of eGFR from preoperative
      value was 13.9 ml/min. This was not significantly correlated with PADUA score (p
      = 0.69). The surgical approach was neither a predictor of Trifecta outcome, nor
      of postoperative complications, WIT > 25 min or PSM rate. CONCLUSIONS: SE is an
      effective treatment for highly-complex renal tumors, with a potential key role to
      widen the NSS (nephron sparing surgery) indications according to guidelines.

PMID- 25957968
TI  - Soy protein is beneficial but high-fat diet and voluntary running are detrimental
      to bone structure in mice.
AB  - Physical activity and soy protein isolate (SPI) augmentation have been reported
      to be beneficial for bone health. We hypothesized that combining voluntary
      running and SPI intake would alleviate detrimental changes in bone induced by a
      high-fat diet. A 2 * 2 * 2 experiment was designed with diets containing 16% or
      45% of energy as corn oil and 20% SPI or casein fed to sedentary or running male
      C57BL/6 mice for 14 weeks. Distal femurs were assessed for microstructural
      changes. The high-fat diet significantly decreased trabecular number (Tb.N) and
      bone mineral density (BMD) and increased trabecular separation (Tb.Sp). Soy
      protein instead of casein, regardless of fat content, in the diet significantly
      increased bone volume fraction, Tb.N, connectivity density, and BMD and decreased
      Tb.Sp. Voluntary running, regardless of fat content, significantly decreased bone
      volume fraction, Tb.N, connectivity density, and BMD and increased Tb.Sp. The
      high-fat diet significantly decreased osteocalcin and increased tartrate
      resistant acid phosphatase 5b (TRAP 5b) concentrations in plasma. Plasma
      concentrations of osteocalcin were increased by both SPI and running. Running
      alleviated the increase in TRAP 5b induced by the high-fat diet. These findings
      demonstrate that a high-fat diet is deleterious, and SPI is beneficial to
      trabecular bone properties. The deleterious effect of voluntary running on
      trabecular structural characteristics indicates that there may be a maximal
      threshold of running beyond which beneficial effects cease and detrimental
      effects occur. Increases in plasma osteocalcin and decreases in plasma TRAP 5b in
      running mice suggest that a compensatory response occurs to counteract the
      detrimental effects of excessive running. 

PMID- 25957969
TI  - A note on (+)-catechin.

PMID- 25957971
TI  - Antibacterial activity and mutagenesis of sponge-associated Pseudomonas
      fluorescens H41.
AB  - Marine sponges (phylum Porifera) are well known to harbour a complex and diverse
      bacterial community. Some of these sponge-associated bacteria have been shown to
      be the real producers of secondary metabolites with a wide range of activities
      from antimicrobials to anticancer agents. Previously, we revealed that the strain
      Pseudomonas fluorescens H41 isolated from the sponge Haliclona sp. (collected at
      the coast of Rio de Janeiro, Brazil) showed a strong antimicrobial activity
      against clinical and marine bacteria. Thus, in this study the genes involved in
      the antimicrobial activity of P. fluorescens H41 were identified. To this end, a
      library of mutants was generated via miniTnphoA3 transposon mutagenesis and the
      resulting clones were characterized for their antimicrobial activity. It was
      demonstrated that genes involved in the biosynthesis of the pyoverdine
      siderophore are related to the inhibitory activity of P. fluorescens H41.
      Therefore, this strain might play an important role in the biocontrol of the host
      sponge. 

PMID- 25957970
TI  - From adolescents to adults with congenital heart disease: the role of transition.
AB  - Improved surgical care during the last decades, together with advances in medical
      management, led to a remarkable increase in survival of patients with congenital
      heart disease (CHD). However, aging of the CHD population brings new challenges,
      and loss of follow-up of adolescents and adults with CHD is a major concern. It
      is crucial to optimize the transfer of patients with CHD from paediatric to adult
      health care services to prevent loss to follow-up. The transition process plays a
      central role in the future health and follow-up of the patient. The aim of this
      review is to explain and discuss the clinical impact of the transition process in
      adolescents with CHD. We will also discuss specific CHD adolescents' problems.
      CONCLUSION: Adolescence is a crucial phase for the formation of the personality.
      Understanding and acceptance of the responsibility for health at this stage
      through a transition process with a multidisciplinary team will determine the
      quality of future medical follow-up and probably limit psychosocial issues in
      their adult life. WHAT IS KNOWN: * Aging of the congenital heart disease
      population brings new challenges to the organisation of care. * Loss of follow-up
      is a major concern for patients with congenital heart disease. What is new: * The
      quality of a formal transition process during adolescence will determine future
      outcomes in patients with congenital heart disease.

PMID- 25957972
TI  - Two new species of the genus Micromonospora: Micromonospora palomenae sp. nov.
      and Micromonospora harpali sp. nov. isolated from the insects.
AB  - Two novel actinobacteria, strains NEAU-CX1(T) and NEAU-JC6(T), were isolated from
      nymphs of stinkbug (Palomena viridissima Poda) and a beetle (Harpalus sinicus
      Hope), respectively, collected from Harbin, Heilongjiang Province, China. A
      polyphasic study was carried out to establish the taxonomic positions of these
      strains. The phylogenetic analysis based on 16S rRNA gene sequence of strain NEAU
      CX1(T) showed it to be most closely related to Micromonospora coxensis JCM
      13248(T) (99.3 % sequence similarity), Micromonospora purpureochromogenes DSM
      43821(T) (99.1 %) and Micromonospora halophytica JCM 3125(T) (98.6 %), and that
      of strain NEAU-JC6(T) to Micromonospora haikouensis DSM 45626(T) (99.3 %),
      Micromonospora carbonacea JCM 3139(T) (99.1 %) and Micromonospora krabiensis JCM
      12869(T) (99.1 %). The phylogenetic analysis based on gyrB gene sequence of
      strain NEAU-CX1(T) showed it to be most closely related to M. purpureochromogenes
      DSM 43821(T) (98.0 % sequence similarity), and that of strain NEAU-JC6(T) to M.
      haikouensis DSM 45626(T) (99.0 %) and M. carbonacea JCM 3139(T) (98.0 %). A
      combination of DNA-DNA hybridization results and cultural and physiological
      properties indicated that the two strains can be distinguished from their closest
      phylogenetic relatives. Thus, strains NEAU-CX1(T) and NEAU-JC6(T) represent two
      novel species of the genus Micromonospora, for which the names Micromonospora
      palomenae sp. nov. and Micromonospora harpali sp. nov. are proposed. The type
      strains are NEAU-CX1(T) (=CGMCC 4.7175(T) = JCM 30056(T)) and NEAU-JC6(T) (=CGMCC
      4.7173(T) = JCM 30055(T)).

PMID- 25957973
TI  - Risk factors for visible lesions or positive laboratory tests in bovine
      tuberculosis reactor cattle in Northern Ireland.
AB  - An observational case-control study was conducted to investigate risk factors for
      confirmed bovine tuberculosis (bTB) infection in cattle reacting positively to
      the single intradermal comparative cervical test (SICCT) in Northern Ireland in
      the years 1998, 2002 and 2006. Macroscopic lesions were detected at slaughter
      (positive visible lesion (VL) status) in 43.0% of reactor cattle, whilst 45.3% of
      those sampled were confirmed as bTB positive due to the presence of lesions or
      positive histopathology/mycobacterial culture (positive bTB status). In 97.5% of
      the reactors, the VL status and bTB status were either both negative or both
      positive. Generalized linear mixed model analyses were conducted on data of
      24,923 reactor cattle with the variables herd identifier, local veterinary office
      (DVO) and abattoir being used as random effects within all the models generated
      at univariable and multivariable level. The other variables within the dataset
      were used as fixed effects. Significant risk factors associated with VL status
      and bTB status at multivariable level (p<0.05) included age at death, breed, sex,
      test year, net increase in skin thickness at bovine tuberculin injection site,
      epidemiological status of skin test, total number of reactors at the disclosure
      test, mean herd size and prior response to the skin test. These risk factors are
      likely related to the time since infection, the strength of the challenge of
      infection and the susceptibility of the animal. These findings are important as
      the detection of visible lesions and the confirmation of bTB are an integral part
      of the overall bTB control programme in Northern Ireland and the veterinary meat
      inspection and hygiene programme. The visible lesion status and bTB status of an
      animal can affect the way in which bTB breakdowns are managed, since failure to
      detect visible lesions and recovery of Mycobacterium bovis can lead to a less
      stringent follow-up after other risk factors have been taken into account. 

PMID- 25957974
TI  - Associations of peripartum markers of stress and inflammation with milk yield and
      reproductive performance in Holstein dairy cows.
AB  - The objective was to evaluate the association of peripartum concentrations of
      fecal cortisol metabolites (11,17-dioxoandrostane; 11,17-DOA), plasma cortisol
      and haptoglobin (Hp), as well as two markers of negative energy balance, non
      esterified fatty acid (NEFA) and postpartum beta-hydroxybutyrate (BHBA), with
      milk yield and reproductive performance. Blood and fecal samples were collected
      weekly from 412 Holstein dairy cows from wk -3 through wk +1 relative to calving.
      Pregnancies by 150 days in milk (DIM) and projected 305-d mature equivalent
      (305ME) milk yield based on the 3rd Dairy Herd Improvement (DHI) test day (mean+/
      SD; 102+/-17 DIM) were measured. Multivariable linear regression models were used
      to describe the associations of metabolites with 305ME milk yield. Semiparametric
      proportional hazards models were used to describe associations of the same
      metabolites with risk of conception by 150 DIM. Negative associations with milk
      yield were found for prepartum Hp in wk -2, -1, and +1 relative to calving
      (estimate+/-SE: 490+/-251, 564+/-259, and 464+/-136kg lower yield for every
      increase in Hp concentration by 1g/L, respectively) as well as with NEFA
      concentration in wk -2 (estimate+/-SE: 1465+/-541kg lower milk yield for an
      increase in NEFA concentration by 1mEq/L). Postpartum associations of NEFA with
      milk yield depended on parity; NEFA was associated with an increase in milk yield
      in primiparous animals only (estimate+/-SE: 1548+/-510kg increase for an increase
      in NEFA concentration by 1mEq/L). An increase in plasma cortisol concentration by
      1MUg/dL in wk +1 relative to calving was associated with an increase in milk
      yield (estimate+/-SE: 580+/-176kg). Prepartum 11,17-DOA was associated in all
      three prepartum sampling weeks with a reduced hazard ratio (HR) of conception (HR
      [95% CI]: 0.81 [0.67-0.97], 0.85 [0.72-0.99], and 0.85 [0.75-0.97] for every
      increase in concentration by 1mg/g fecal dry matter (DM) in wk -3, -2, and -1
      relative to calving, respectively). Increased cortisol concentrations in wk -3
      and -1 relative to calving were associated with decreased hazard of conception in
      primiparous animals only (HR [95% CI]: 0.54 [0.32-0.92] and 0.59 [0.35-0.99],
      respectively. Increases in postpartum metabolites Hp and BHBA had a negative
      association with hazard of conception (HR [95% CI]: 0.81 [0.70-0.97], 0.74 [0.56
      0.98], respectively). Biomarkers of inflammation and stress around calving may be
      useful to assess opportunities for improved milk yield and reproduction. 

PMID- 25957975
TI  - Developing a salinity-based approach for the evaluation of DIN removal rate in
      estuarine ecosystems.
AB  - Estuaries play an important role in the removal of overloading nitrogen to
      relieve the eutrophic pressure of coastal seawater. However, the exact amount of
      nitrogen removed in estuarine ecosystems is difficult to be estimated because of
      the complex dynamic mixing process between riverine water and coastal seawater.
      In this study, a new method was developed to calculate the removal rate of
      dissolved inorganic nitrogen (DIN) in estuarine waters attributed to the mixing
      process and was based on the assumption that relative salinity can serve as an
      indicator of the degree of mixing. This assumption was supported by the
      experimental results that demonstrated a linear regression relationship between
      DIN decline and salinity increase Thus, the decreased amount of DIN in mixing
      waters attributed to the dilution effect could be determined with the salinity as
      an index. With this model, the DIN removal rate in both Chesapeake Bay and Pearl
      River Estuary were defined. As predicted, our analysis demonstrated that the DIN
      removal rate increased gradually from upstream to downstream in both studied
      estuaries with obvious seasonable variation pattern: high in warm seasons and low
      in cold seasons. The practical application of this method might be affected by
      multiple factors, including the geographic landform of estuaries, initial
      estuaries DIN concentration, the DIN concentration in seawater, DIN importing
      from tributaries, sewage discharge and hydrodynamic mixing. Therefore, the
      results supported the hypothesis that estuaries have a strong capability to
      remove the nitrogen inputted from human activities, especially in warm season and
      therefore should play an important role in regulating the balance of global
      nitrogen biogeochemical cycle.

PMID- 25957976
TI  - Hypertension Prevalence, Cardiac Complications, and Antihypertensive Medication
      Use in Children.
AB  - OBJECTIVE: To determine the prevalence of hypertension diagnosis in children of
      US military members and quantify echocardiography evaluations, cardiac
      complications, and antihypertensive prescriptions in the post-2004 guideline era.
      STUDY DESIGN: Using billing data from military health insurance (TRICARE)
      enrollees, hypertension cases were defined as 2 or more visits with a primary or
      unspecified hypertension diagnosis during any calendar year or 1 such visit if
      with a cardiologist or nephrologist. RESULTS: During 2006-2011, the database
      contained an average 1.3 million subjects aged 2-18 years per year. A total of 16
      322 met the definition of hypertension (2.6/1000). The incidence of hypertension
      increased by 17% between 2006 and 2011 (from 2.3/1000 to 2.7/1000; P < .001).
      Hypertension was more common in adolescents aged 12-18 years than in younger
      children (5.4/1000 vs 0.9/1000). Among patients with hypertension, 5585 (34%)
      underwent echocardiography. The frequency of annual echocardiograms increased
      from 22.7% to 27.7% (P < .001). In patients with echocardiography, 8.0% had left
      ventricular hypertrophy or dysfunction. Among the patients with hypertension,
      6353 (38.9%) received an antihypertensive medication. CONCLUSION: The prevalence
      of hypertension in children has increased. Compliance with national guidelines is
      poor. Of pediatric patients with hypertension who receive an echocardiogram, 1 in
      12 had identified cardiac complications, supporting the current recommendations
      for echocardiography in children with hypertension. Less than one-half of
      children with hypertension are treated with medication.

PMID- 25957977
TI  - Recommendations from the Pediatric Endocrine Society for Evaluation and
      Management of Persistent Hypoglycemia in Neonates, Infants, and Children.

PMID- 25957978
TI  - Mask versus Nasal Tube for Stabilization of Preterm Infants at Birth: Respiratory
      Function Measurements.
AB  - OBJECTIVE: To compare the nasal tube with face mask as interfaces for
      stabilization of very preterm infants at birth by using physiological
      measurements of leak, obstruction, and expired tidal volumes during positive
      pressure ventilation (PPV). STUDY DESIGN: In the delivery room, 43 infants <30
      weeks gestation were allocated to receive respiratory support by nasal tube or
      face mask. Respiratory function, heart rate, and oxygen saturation were measured.
      Occurrence of obstruction, amount of leak, and tidal volumes were compared using
      a Mann-Whitney U test or a Fisher exact test. RESULTS: The first 5 minutes after
      initiation of PPV were analyzed (1566 inflations in the nasal tube group and 1896
      inflations in the face mask group). Spontaneous breathing coincided with PPV in
      32% of nasal tube and 34% of face mask inflations. During inflations, higher leak
      was observed using nasal tube compared with face mask (98% [33%-100%] vs 14 [0%
      39%]; P < .0001). Obstruction occurred more often (8.2% vs 1.1%; P < .0001).
      Expired tidal volumes were significantly lower during inflations when using nasal
      tube compared with face mask (0.0 [0.0-3.1] vs 9.9 [5.5-12.8] mL/kg; P < .0001)
      and when spontaneous breathing coincided with PPV (4.4 [2.1-8.4] vs 9.6 [5.4
      15.2] mL/kg; P < .0001) but were similar during breathing on continuous positive
      airway pressure (4.7 [2.8-6.9] vs 4.8 [2.7-7.9] mL/kg; P > 0.05). Heart rate was
      not significantly different between groups, but oxygen saturation was
      significantly lower in the nasal tube group the first 2 minutes after start of
      respiratory support. CONCLUSIONS: The use of a nasal tube led to large leak, more
      obstruction, and inadequate tidal volumes compared with face mask. TRIAL
      REGISTRATION: Trial registration Registered with the Dutch Trial Registry (NTR
      2061) and the Australia and New Zealand Clinical Trials Register (ACTRN
      12610000230055).

PMID- 25957979
TI  - Zymosan Induces Immune Responses Comparable with Those of Adults in Monocytes,
      Dendritic Cells, and Monocyte-Derived Dendritic Cells from Cord Blood.
AB  - OBJECTIVE: To investigate the differences in toll-like receptor (TLR)-mediated
      immune responses between human neonates and adults, focusing on the cytokine
      profiles of monocytes, dendritic cells (DCs), and monocyte-derived DCs (MoDCs) in
      cord and adult blood. STUDY DESIGN: Purified monocytes, DCs, and MoDCs were
      stimulated with the following TLR ligands: lipopolysaccharide (TLR4), Pam3CSK4
      (TLR1/2), flagellin (TLR5), zymosan (TLR2), polyinosinic:polycytidylic acid
      (TLR3), imiquimod (TLR7), and CpG (TLR9). Interleukin (IL)-8, IL-6, tumor
      necrosis factor, IL-1beta, and IL-10 concentrations were analyzed in culture
      supernatants. RESULTS: Compared with the effects in adult blood,
      lipopolysaccharide-, Pam3CSK4-, flagellin-, and polyinosinic:polycytidylic acid
      stimulated inflammatory cytokine production in cord blood was generally weak in
      monocytes, comparable in DCs, and elevated in MoDCs. CpG- and imiquimod
      stimulated cytokine production in DCs was comparable in cord blood and adult
      blood, but cytokine production was almost absent in monocytes and MoDCs in both
      cord blood and adult blood. In contrast, zymosan stimulation produced comparable
      inflammatory cytokine profiles in the monocytes, DCs, and MoDCs of cord blood and
      adult blood. CONCLUSION: The immaturity of TLR-mediated innate immunity in
      neonates depends on monocytes rather than on DCs. Our results indicate that
      zymosan-mediated TLR2 signaling may be useful for developing a neonatal vaccine
      adjuvant.

PMID- 25957980
TI  - Patient-reported outcome assessment after total joint replacement: comparison of
      questionnaire completion times on paper and tablet computer.
AB  - INTRODUCTION: Patient-reported outcome (PRO) assessment is becoming increasingly
      important after joint replacement surgery. However, PRO data collection,
      questionnaire handling, and data processing are time consuming and costly
      process. The aim of our study was to evaluate the efficiency of PRO assessment
      using tablet computers compared with traditional paper questionnaires in a total
      hip or knee arthroplasty (THR or TKR) population. MATERIALS AND METHODS: We
      recruited 100 patients from outpatient clinics attending for routine follow-up 2
      months, 1 year, or 5 years after THR or TKR. Fifty patients completed the Western
      Ontario and McMaster Universities (WOMAC) osteoarthritis score and Forgotten
      Joint Score-12 (FJS-12) questionnaires on paper, and 50 patients completed these
      on a tablet computer. Questionnaire completion was timed for each PRO assessment
      and for manual data entry of the paper questionnaires into the database. The t
      test, Mann-Whitney U test, Fisher's exact test, and Wilcoxon test were used for
      statistical analysis. RESULTS: The mean age of the patients was 67.0 years
      (standard deviation 10.3 years), with no significant difference between the two
      groups. Median time for WOMAC questionnaire completion (including data entry for
      the paper questionnaires) was 197 s for the paper version and 117 s for the
      tablet version (p < 0.001). Median times for completion of FJS-12 were comparable
      for paper and tablet versions (32 vs. 37 s). We did not find a significant
      correlation between age and time for questionnaire completion. CONCLUSION:
      Electronic PRO data collection can substantially decrease time, logistics, and
      effort associated with questionnaire completion in daily clinical practice. It is
      also acceptable for use in an older arthroplasty population.

PMID- 25957981
TI  - Does intraoperative application of leukocyte-poor platelet-rich plasma during
      arthroscopy for knee degeneration affect postoperative pain, function and quality
      of life? A 12-month randomized controlled double-blind trial.
AB  - INTRODUCTION: We aimed to identify the effects of intraoperative applied
      leukocyte-poor platelet-rich plasma (LP-PRP) during knee arthroscopy for
      degenerative lesions involving pain, function and quality of life. METHODS: We
      performed a randomized controlled, double-blind trial (RCT) including 58 patients
      for arthroscopic knee surgery for cartilage or meniscal degeneration with
      allocation into the LP-PRP (n = 24) or control group (n = 34). During
      arthroscopy, LP-PRP was injected intra-articular in the intervention group. At
      baseline, 6 weeks, 6 months and 12 months pain, function, and life quality were
      assessed. RESULTS: 91 % of enrolled patients were available for 12 months follow
      up. Pain was significantly lower in the LP-PRP group (VAS 0.9. vs. 2.3) at 6 (p =
      0.008) but not at 12 months (VAS 1.0 vs. 1.6, p = 0.063). LP-PRP application
      improved the Lysholm Score at 6 (77.5 vs. 65.6, p = 0.033) and 12 months (83.2
      vs.70.0, p = 0.007). Assessment of life quality (SF-36) concerning the physical
      component summary was significantly higher at 6 weeks (33.9 vs. 25.6, p = 0.001)
      and 6 months (29.9 vs. 27.1, p = 0.027) in the LP-PRP group but equal at 1 year
      (31.4 vs. 30.1, p = 0.438). CONCLUSIONS: Intraoperative application of LP-PRP may
      enhance pain reduction and gain of knee function within 6-12 months compared to
      arthroscopy alone. LEVEL OF EVIDENCE: II, randomized controlled clinical trial
      with reduced power. CLINICALTRIALS. GOV IDENTIFIER: NCT02189408.

PMID- 25957982
TI  - The course of the median and radial nerve across the elbow: an anatomic study.
AB  - INTRODUCTION: Nerve transection has been described as complication of
      arthroscopic elbow arthrolysis. Therefore, the goal of this study was to define
      bony landmarks for intraoperative orientation regarding the location of the
      median and radial nerve. METHODS: In 22 formalin-fixated upper extremities, the
      radial and median nerves were dissected and marked with respect to their native
      course. A 3D X-ray scan was performed. The distances of the radial nerve to the
      radial head (R1), the capitulum (R2), and its lateral border (RC) were measured.
      The location of the radial nerve in relation to the transversal diameter of the
      humeral condyle (HC) was calculated. Similarly, the distances of the median nerve
      to the trochlea (M1), the medial border of the trochlea (M2), and its relation to
      HC were calculated. RESULTS: The mean value for R1 was 8 mm (+/-2.9 mm), for R2
      was 11.3 mm (+/-3.8 mm), and for RC was 10.6 mm (+/-5.1 mm). RC/HC averaged 24 %
      (+/-11 %). M1 averaged 11.7 mm (+/-5.2 mm), and M2 was 2.4 mm (+/-4.1 mm). M2/HC
      averaged 6 % (+/-9 %). CONCLUSIONS: The radial nerve is located ventral to the
      central third of the capitulum. The median nerve lies ventral to the medial
      quarter of the humeral condyle. When performing arthroscopic arthrolysis, this
      information should be kept in mind during anterior capsulectomy.

PMID- 25957983
TI  - A new universal, standardized implant database for product identification: a
      unique tool for arthroplasty registries.
AB  - INTRODUCTION: Every joint registry aims to improve patient care by identifying
      implants that have an inferior performance. For this reason, each registry
      records the implant name that has been used in the individual patient. In most
      registries, a paper-based approach has been utilized for this purpose. However,
      in addition to being time-consuming, this approach does not account for the fact
      that failure patterns are not necessarily implant specific but can be associated
      with design features that are used in a number of implants. Therefore, we aimed
      to develop and evaluate an implant product library that allows both time saving
      barcode scanning on site in the hospital for the registration of the implant
      components and a detailed description of implant specifications. MATERIALS AND
      METHODS: A task force consisting of representatives of the German Arthroplasty
      Registry, industry, and computer specialists agreed on a solution that allows
      barcode scanning of implant components and that also uses a detailed standardized
      classification describing arthroplasty components. The manufacturers classified
      all their components that are sold in Germany according to this classification.
      The implant database was analyzed regarding the completeness of components by
      algorithms and real-time data. RESULTS: The implant library could be set up
      successfully. At this point, the implant database includes more than 38,000
      items, of which all were classified by the manufacturers according to the
      predefined scheme. Using patient data from the German Arthroplasty Registry,
      several errors in the database were detected, all of which were corrected by the
      respective implant manufacturers. CONCLUSIONS: The implant library that was
      developed for the German Arthroplasty Registry allows not only on-site barcode
      scanning for the registration of the implant components but also its
      classification tree allows a sophisticated analysis regarding implant
      characteristics, regardless of brand or manufacturer. The database is maintained
      by the implant manufacturers, thereby allowing registries to focus their
      resources on other areas of research. The database might represent a possible
      global model, which might encourage harmonization between joint replacement
      registries enabling comparisons between joint replacement registries.

PMID- 25957984
TI  - Perioperative implications and management of dextrocardia.
AB  - Dextrocardia, a term used to describe all varieties of developmental
      malformations resulting in the positioning of the heart in the right hemithorax,
      is linked to a number of highly significant cardiac disorders. Current estimates
      vary tremendously in the literature. Only about 10 % of patients with diagnosed
      dextroversion show no substantial cardiac pathology; however, the incidence of
      congenital heart defects associated with dextrocardia is close to 100 %. The
      majority of studies previously reported include dextrocardia associated with
      situs inversus and cases of Kartagener syndrome. There is complex embryology and
      pathogenesis that results in dextrocardia. Physical examinations of the heart,
      such as percussion and palpation during routine exams, are vitally important
      initial diagnostic instruments. X-ray, CT scan, echocardiography (ECHO), and MRI
      are all invaluable imaging modalities to confirm and classify the diagnosis of
      dextrocardia. In summary, heart malposition is a group of complex pathologic
      associations within the human body, rather than just a single congenital defect.
      Clinicians such as anesthesiologists have unique challenges managing patients
      with dextrocardia. An appreciation of associated pathogenesis, appropriate
      diagnosis, and management is paramount in ensuring the best outcome for these
      patients perioperatively.

PMID- 25957986
TI  - Short-term storage stability of serum angiotensin-converting enzyme (ACE)
      activity.

PMID- 25957987
TI  - Circadian-relevant genes are highly polymorphic in autism spectrum disorder
      patients.
AB  - BACKGROUND: The genetic background of autism spectrum disorder (ASD) is
      considered a multi-genetic disorder with high heritability. Autistic children
      present with a higher prevalence of sleep disorders than has been observed in
      children with normal development. Some circadian-relevant genes have been
      associated with ASD (e.g., PER1, PER2, NPAS2, MTNR1A, and MTNR1B). METHODS: We
      analyzed 28 ASD patients (14 with sleep disorders and 14 without) and 23 control
      subjects of Japanese descent. The coding regions of 18 canonical clock genes and
      clock-controlled genes were sequenced. Detected mutations were verified by direct
      sequencing analysis, and additional control individuals were screened. RESULTS:
      Thirty-six base changes with amino acid changes were detected in 11 genes. Six
      missense changes were detected only in individuals with ASD with sleep
      disturbance: p.F498S in TIMELESS, p.S20R in NR1D1, p.R493C in PER3, p.H542R in
      CLOCK, p.L473S in ARNTL2, and p.A325V in MTNR1B. Six missense changes were
      detected only in individuals with ASD without sleep disturbance: p.S1241N in
      PER1, p.A325T in TIMELESS, p.S13T in ARNTL, p.G24E in MTNR1B, p.G24E in PER2, and
      p.T1177A in PER3. The p.R493C mutation in PER3 was detected in both groups. One
      missense change, p.P932L in PER2, was detected only in the control group.
      Mutations in NR1D1, CLOCK, and ARNTL2 were detected only in individuals with ASD
      with sleep disorder. The prevalence of the mutations detected only single time
      differed significantly among all ASD patients and controls (p=0.003). Two kinds
      of mutations detected only in individuals with ASD with sleep disorder, p.F498S
      in TIMELESS and p.R366Q in PER3, were considered to affect gene function by three
      different methods: PolyPhen-2, scale-invariant feature transform (SIFT)
      prediction, and Mutation Taster (www.mutationtaster.org). The mutations p.S20R in
      NR1D1, p.H542R in CLOCK, p.L473S in ARNTL2, p.A325T in TIMELESS, p.S13T in ARNTL,
      and p.G24E in PER2 were diagnosed to negatively affect gene function by more than
      one of these methods. CONCLUSION: Mutations in circadian-relevant genes affecting
      gene function are more frequent in patients with ASD than in controls. Circadian
      relevant genes may be involved in the psychopathology of ASD.

PMID- 25957989
TI  - Awareness, time and dimensions and their link to Medical Radiation Physics and
      Radiation Oncology.

PMID- 25957985
TI  - Somatosensory evoked potentials in the assessment of peripheral neuropathies:
      Commented results of a survey among French-speaking practitioners and
      recommendations for practice.
AB  - BACKGROUND: Somatosensory evoked potentials (SSEPs) are increasingly performed
      for the assessment of peripheral neuropathies, but no practical guidelines have
      yet been established in this specific application. STUDY AIM: To determine the
      relevant indication criteria and optimal technical parameters for SSEP recording
      in peripheral neuropathy investigation. METHODS: A survey was conducted among the
      French-speaking practitioners with experience of SSEP recording in the context of
      peripheral neuropathies. The results of the survey were analyzed and discussed to
      provide recommendations for practice. RESULTS: SSEPs appear to be a second-line
      test when electroneuromyographic investigation is not sufficiently conclusive,
      providing complementary and valuable information on central and proximal
      peripheral conduction in the somatosensory pathways. CONCLUSIONS: Guidelines for
      a standardized recording protocol, including the various parameters to be
      measured, are proposed. CLINICAL RELEVANCE: We hope that these proposals will
      help to recognize the value of this technique in peripheral neuropathy assessment
      in clinical practice.

PMID- 25957988
TI  - Control of emerging extensively drug-resistant organisms (eXDRO) in France: a
      survey among infection preventionists from 286 healthcare facilities.
AB  - We performed a multicenter survey in May-June 2012 to assess strategies in
      preventing the spread of emerging extensively drug-resistant organisms (eXDRO),
      including glycopeptide-resistant enterococci and carbapenemase-producing
      Enterobacteriaceae, in a convenient sample of French healthcare facilities
      (HCFs). The collected data included organization and measures to: (1) identify
      patients at risk for carrying eXDRO, (2) investigate and control sporadic cases
      or outbreaks, and (3) describe prior 2010-2012 episodes with one or more
      colonized patients. Of the 286 participating HCFs, 163 (57 %) and 134 (47 %)
      reported having a specific procedure to detect repatriates or patients
      hospitalized in foreign countries within the last year, respectively. Among the
      97 HCFs with prior at-risk patient management experience, contact precautions,
      hospitalization in a single room, and screening for eXDRO carriage were quasi
      systematically performed (n = 92/97, 95 %). The alleged time between admission
      and alert ranged from 24 to 48 h after the patient's admission; 203 (71 %) HCFs
      recommended obtaining three successive negative screening samples to declare a
      patient free of eXDRO colonization. During the last two years, 64 HCFs (23 %) had
      to manage at least one eXDRO case, with a total of 20 outbreaks with more than
      one secondary case. This first national survey shows that French HCFs were not
      totally ready to control eXDRO spread in 2012. Their previous experiences and
      capacities in controlling eXDRO outbreaks are quite heterogeneous from one
      hospital to another. Further researches are needed in order to understand the
      constraints in applying national guidance. 

PMID- 25957990
TI  - Scintillation properties of the YVO4:Eu3+ compound in powder form: its
      application to dosimetry in radiation fields produced by pulsed mega-voltage
      photon beams.
AB  - The investigation of scintillation properties of europium doped yttrium
      orthovanadate shows the suitability of this material for fiber-based dose rate
      measurements. All measurements were carried out with a 6 MV Varian linear
      accelerator. The temperature dependence of the signal is lower than that of the
      plastic scintillators reported so far. By measuring the afterglow of probes
      between Linac-pulses, the signal due to the stem effect can be successfully
      eliminated. Comparison of depth dose profiles in a water phantom for radiation
      field dimensions between 1 x 1 cm(2) and 10 x 10 cm(2) shows that the probes are
      suitable for small fields having dimensions up to 1 x 1 cm(2). The high light
      yield of probes having dimensions of 1 mm opens up the possibility for their use
      in spatially confined radiation fields, such as in intensity-modulated
      radiotherapy (IMRT) and volume-modulated radiation therapy (VMAT). 

PMID- 25957992
TI  - Conflict awareness dissociates theta-band neural dynamics of the medial frontal
      and lateral frontal cortex during trial-by-trial cognitive control.
AB  - Recent findings have refuted the common assumption that executive control
      functions of the prefrontal cortex exclusively operate consciously, suggesting
      that many, if not all, cognitive processes could potentially operate
      unconsciously. However, although many cognitive functions can be launched
      unconsciously, several theoretical models of consciousness assume that there are
      crucial qualitative differences between conscious and unconscious processes. We
      hypothesized that the potential benefit of awareness in cognitive control
      mechanisms might become apparent when high control has to be maintained across
      time and requires the interaction between a set of distant frontal brain regions.
      To test this, we extracted oscillatory power dynamics from
      electroencephalographic data recorded while participants performed a task in
      which conflict awareness was manipulated by masking the conflict-inducing
      stimulus. We observed that instantaneous conflict as well as across trial
      conflict adaptation mechanisms were associated with medial frontal theta-band
      power modulations, irrespective of conflict awareness. However, and crucially,
      across-trial conflict adaptation processes reflected in increased theta-band
      power over dorsolateral frontal cortex were observed after fully conscious
      conflict only. This suggests that initial conflict detection and subsequent
      control adaptation by the medial frontal cortex are automatic and unconscious,
      whereas the routing of information from the medial frontal cortex to the lateral
      prefrontal cortex is a unique feature of conscious cognitive control. 

PMID- 25957991
TI  - Brain structure correlates of emotion-based rash impulsivity.
AB  - Negative urgency (the tendency to engage in rash, ill-considered action in
      response to intense negative emotions), is a personality trait that has been
      linked to problematic involvement in several risky and impulsive behaviours, and
      to various forms of disinhibitory psychopathology, but its neurobiological
      correlates are poorly understood. Here, we explored whether inter-individual
      variation in levels of trait negative urgency was associated with inter
      individual variation in regional grey matter volumes. Using voxel-based
      morphometry (VBM) in a sample (n=152) of healthy participants, we found that
      smaller volumes of the dorsomedial prefrontal cortex and right temporal pole,
      regions previously linked to emotion appraisal, emotion regulation and emotion
      based decision-making, were associated with higher levels of trait negative
      urgency. When controlling for other impulsivity linked personality traits
      (sensation seeking, lack of planning/perseverance) and negative emotionality per
      se (neuroticism), these associations remained, and an additional relationship was
      found between higher levels of trait negative urgency and smaller volumes of the
      left ventral striatum. This latter finding mirrors recent VBM findings in an
      animal model of impulsivity. Our findings offer novel insight into the brain
      structure correlates of one key source of inter-individual differences in
      impulsivity. 

PMID- 25957993
TI  - Interactive effects of citalopram and serotonin transporter genotype on neural
      correlates of response inhibition and attentional orienting.
AB  - The brain's serotonergic (5-HT) system has been implicated in controlling
      impulsive behavior and attentional orienting and linked to impulse control and
      anxiety related disorders. However, interactions between genotypical variation
      and responses to serotonergic drugs impede both treatment efficacy and
      neuroscientific research. We examine behavioral and electrophysiological
      responses to acute intravenous administration of a selective serotonin reuptake
      inhibitor (SSRI) while controlling for major genetic differences regarding 5-HT
      transporter (5-HTT) genotypes. Out of a genotyped sample of healthy Caucasian
      subjects (n=878) two extreme-groups regarding 5-HTT genotypes were selected
      (n=32). A homozygous high-expressing group based on tri-allelic 5-HTTLPR and
      rs25532 (LAC/LAC=LL) was compared to homozygous S allele carriers (SS). Both
      groups were administered a low dose of citalopram (10mg) intravenously in a
      double blind crossover fashion and performed a novelty NoGo paradigm while high
      density EEG was recorded. Interactions between drug and genotype were seen on
      both behavioral and neurophysiological levels. Reaction slowing following
      inhibitory events was decreased by the administration of citalopram in the LL but
      not SS group. This was accompanied by decreases in the amplitude of the
      inhibitory N2 EEG component and the P3b in the LL group, which was not seen in
      the SS group. SS subjects showed an increase in P3a amplitudes following SSRI
      administration to any type of deviant stimulus possibly reflecting increased
      attentional capture. The acute SSRI response on inhibitory processes and
      attentional orienting interacts with genotypes regulating 5-HTT gene expression.
      SS subjects may show increased attentional side effects reflected in increases in
      P3a amplitudes which could contribute to treatment discontinuation. Inhibitory
      processes and their neural correlates are affected only in LL subjects. These
      findings may indicate an underlying mechanism that could relate genotypical
      differences to altered side effect profiles and drug responses and are compatible
      with a non-monotonic relationship between 5-HT levels and optimal functioning. 

PMID- 25957994
TI  - Image-guided left ventricular lead placement in cardiac resynchronization therapy
      for patients with heart failure: a meta-analysis.
AB  - BACKGROUND: Heart failure (HF) is a debilitating condition that affects millions
      of people worldwide. One means of treating HF is cardiac resynchronization
      therapy (CRT). Recently, several studies have examined the use of
      echocardiography (ECHO) in the optimization of left ventricular (LV) lead
      placement to increase the response to CRT. The objective of this study was to
      synthesize the available data on the comparative efficacy of image-guided and
      standard CRT. METHODS: We searched the PubMed, Cochrane, Embase, and ISI Web of
      Knowledge databases through April 2014 with the following combinations of search
      terms: left ventricular lead placement, cardiac resynchronization therapy, image
      guided, and echocardiography-guided. Studies meeting all of the inclusion
      criteria and none of the exclusion criteria were eligible for inclusion. The
      primary outcome measures were CRT response rate, change in LV ejection fraction
      (LVEF), and change in LV end systolic volume (LVESV). Secondary outcomes included
      the rates of all-cause mortality and HF-related hospitalization. RESULTS: Our
      search identified 103 articles, 3 of which were included in the analysis. In
      total, 270 patients were randomized to the image-guided CRT and 241, to the
      standard CRT. The pooled estimates showed a significant benefit for image-guided
      CRT (CRT response: OR, 2.098, 95 % CI, 1.432-3.072; LVEF: difference in means,
      3.457, 95 % CI, 1.910-5.005; LVESV: difference in means, -20.36, 95 % CI, -27.819
      - -12.902). CONCLUSIONS: Image-guided CRT produced significantly better clinical
      outcomes than the standard CRT. Additional trials are warranted to validate the
      use of imaging in the prospective optimization of CRT.

PMID- 25957995
TI  - A patient-specific model of the biomechanics of hip reduction for neonatal
      Developmental Dysplasia of the Hip: Investigation of strategies for low to severe
      grades of Developmental Dysplasia of the Hip.
AB  - A physics-based computational model of neonatal Developmental Dysplasia of the
      Hip (DDH) following treatment with the Pavlik Harness (PV) was developed to
      obtain muscle force contribution in order to elucidate biomechanical factors
      influencing the reduction of dislocated hips. Clinical observation suggests that
      reduction occurs in deep sleep involving passive muscle action. Consequently, a
      set of five (5) adductor muscles were identified as mediators of reduction using
      the PV. A Fung/Hill-type model was used to characterize muscle response. Four
      grades (1-4) of dislocation were considered, with one (1) being a low subluxation
      and four (4) a severe dislocation. A three-dimensional model of the pelvis-femur
      lower limb of a representative 10 week-old female was generated based on CT-scans
      with the aid of anthropomorphic scaling of anatomical landmarks. The model was
      calibrated to achieve equilibrium at 90 degrees  flexion and 80 degrees 
      abduction. The hip was computationally dislocated according to the grade under
      investigation, the femur was restrained to move in an envelope consistent with PV
      restraints, and the dynamic response under passive muscle action and the effect
      of gravity was resolved. Model results with an anteversion angle of 50 degrees 
      show successful reduction Grades 1-3, while Grade 4 failed to reduce with the PV.
      These results are consistent with a previous study based on a simplified
      anatomically-consistent synthetic model and clinical reports of very low success
      of the PV for Grade 4. However our model indicated that it is possible to achieve
      reduction of Grade 4 dislocation by hyperflexion and the resultant external
      rotation. 

PMID- 25957996
TI  - The Effect of miR-132, miR-146a, and miR-155 on MRP8/TLR4-Induced Astrocyte
      Related Inflammation.
AB  - Astrocyte activation, associated with the release of pro-inflammatory cytokines
      interleukin 1-beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor
      alpha (TNF-alpha), is a hallmark of multiple brain diseases, including mesial
      temporal lobe epilepsy. In recent years, several microRNAs have emerged as
      important controllers of Toll-like receptor (TLR) signaling. In this study, we
      investigated the effect of miR-132, miR-146a, and miR-155 on myeloid-related
      protein-8 (MRP8) induced astrocyte-related inflammation. Using quantitative
      polymerase chain reaction (qPCR) and western blot, we found clear upregulation of
      TLR4 and downstream inflammatory cytokines, along with dysregulation of miR-132,
      miR-146a, and miR-155 in in vitro astrocytes after exposing them to different
      concentrations of MRP8. In addition, we focused on the effect of miR-132 on
      astrocyte-related inflammation induced by MRP8 via lentiviral infection then
      evaluated the expression of its possible target genes: acetylcholinesterase
      (AChE) and interleukin-1 receptor-associated kinase (IRAK4). Our results show
      that miR-132 is a negative feedback regulator of IL-1beta and IL-6, but not TNF
      alpha, by targeting IRAK4. Together, our findings demonstrate the novel role of
      TLR4-related microRNAs, especially miR-132, in the regulation of MRP8-induced
      astrocyte activation and highlight the importance of miR-132 in the modulation of
      innate immune response induced by endogenous ligands in neurological diseases. 

PMID- 25957997
TI  - Nur77 Was Essential for Neurite Outgrowth and Involved in Schwann Cell
      Differentiation After Sciatic Nerve Injury.
AB  - Nur77, together with Nurr1 and NOR-1, constitutes the NR4A subgroup of orphan
      nuclear receptors and plays critical roles in cell proliferation,
      differentiation, migration, and apoptosis. Among them, Nur77 is universally well
      known to contribute to neurite outgrowth. However, information regarding its
      regulation and possible function in the peripheral nervous system is still
      limited. In this study, we performed a sciatic nerve injury model in adult rats
      and detected an increased expression of Nur77 in the sciatic nerve, which was
      similar to the expression of Oct-6. Immunofluorescence indicated that Nur77 was
      located in both axons and Schwann cells. In vitro, we observed enhanced
      expression of Nur77 during the process of both basic fibroblast growth factor
      (bFGF)-induced Schwann cells differentiation and nerve growth factor (NGF)
      induced PC12 cell neurite outgrowth. In vitro and in vivo experiments indicated
      that inhibiting the function of Nur77 by specific short hairpin RNA could depress
      Schwann cells myelinization and axons regeneration. Collectively, all these
      results suggested that upregulation of Nur77 might be involved in Schwann cells
      differentiation and neurite elongation following sciatic nerve crush. 

PMID- 25957998
TI  - Dietary practices among individuals with diabetes and hypertension are similar to
      those of healthy people: a population-based study.
AB  - BACKGROUND: Currently, diabetes mellitus (DM) and systemic arterial hypertension
      (SAH) are among the top five global risks for mortality. Among the modifiable
      factors, careful dietary practice is one of the essential elements for the
      control of NCDs, since these diseases are often the result of unhealthy
      lifestyles. Thus, this study aimed to assess the frequency of dietary practices
      among adult males and females with DM and/or SAH, and compare whether or not they
      are more frequent than in healthy adults, through a population-based study
      conducted in the city of Florianopolis, southern Brazil. METHODS: Cross-sectional
      population-based study, using as exposure self-reported DM and/or SAH status.
      Dietary practices were assessed using a semiquantitative food consumption
      questionnaire. The following were considered as adequate: regular intake (>= 6
      times/week) of fruit and vegetables, daily intake of fruit (>= 3 times/day) and
      vegetables (>= 2 times/day), intake lower than 2 times/week of meat fat, fried
      foods, and soda. Bivariate and adjusted analysis for sociodemographic variables
      were conducted using Poisson regression, stratified by gender. LOCATION:
      Florianopolis, southern Brazil, 2009. SUBJECTS: Representative sample of 20 to 59
      year-old adults (n=1720). RESULTS: A total of 16.6% participants were diagnosed
      with DM and/or SAH. The most frequently consumed unhealthy foods were fried food
      (51.0%, 95% CI: 48.8-53.5) and soda (57.9% 95%CI: 55.5-60.2). Of healthy foods,
      fruit was the less consumed on a daily basis (11.1% 95%CI 9.6-12.5). In general,
      women showed better dietary practices than men. In adjusted analysis none of
      dietary practices was more frequent among diabetic and/or hypertensive adults
      compared with healthy individuals, regardless of gender. No differences were
      found between healthy and unhealthy adults, when the number of dietary practices
      was assessed. CONCLUSIONS: The frequency of dietary practices was low and did not
      differ between individuals with or without DM and/or SAH. It is fundamental to
      reinforce the need of healthy dietary practices as one of the essential elements
      for the control of chronic diseases and their complications.

PMID- 25957999
TI  - Optimisation of immunofluorescence methods to determine MCT1 and MCT4 expression
      in circulating tumour cells.
AB  - BACKGROUND: The monocarboxylate transporter-1 (MCT1) represents a novel target in
      rational anticancer drug design while AZD3965 was developed as an inhibitor of
      this transporter and is undergoing Phase I clinical trials (
      http://www.clinicaltrials.gov/show/NCT01791595 ). We describe the optimisation of
      an immunofluorescence (IF) method for determination of MCT1 and MCT4 in
      circulating tumour cells (CTC) as potential prognostic and predictive biomarkers
      of AZD3965 in cancer patients. METHODS: Antibody selectivity was investigated by
      western blotting (WB) in K562 and MDAMB231 cell lines acting as positive controls
      for MCT1 and MCT4 respectively and by flow cytometry also employing the control
      cell lines. Ability to detect MCT1 and MCT4 in CTC as a 4(th) channel marker
      utilising the VeridexTM CellSearch system was conducted in both human volunteer
      blood spiked with control cells and in samples collected from small cell lung
      cancer (SCLC) patients. RESULTS: Experimental conditions were established which
      yielded a 10-fold dynamic range (DR) for detection of MCT1 over MCT4 (antibody
      concentration 6.25 MUg/mL; integration time 0.4 seconds) and a 5-fold DR of MCT4
      over MCT 1 (8 MUg/100 MUL and 0.8 seconds). The IF method was sufficiently
      sensitive to detect both MCT1 and MCT4 in CTCs harvested from cancer patients.
      CONCLUSIONS: The first IF method has been developed and optimised for detection
      of MCT 1 and MCT4 in cancer patient CTC.

PMID- 25958000
TI  - Whole-exome sequencing identifies de novo mutation in the COL1A1 gene to underlie
      the severe osteogenesis imperfecta.
AB  - BACKGROUND: Osteogenesis imperfecta (OI) comprises a clinically and genetically
      heterogeneous group of connective tissue disorders, characterized by low bone
      mass, increased bone fragility, and blue-gray eye sclera. OI often results from
      missense mutations in one of the conserved glycine residues present in the Gly-X
      Y sequence repeats of the triple helical region of the collagen type I alpha
      chain, which is encoded by the COL1A1 gene. The aim of the present study is to
      describe the phenotype of OI II patient and a novel mutation, causing current
      phenotype. RESULTS: We report an undescribed de novo COL1A1 mutation in a patient
      affected by severe OI. After performing the whole-exome sequencing in a case
      parent-child trio, we identified a novel heterozygous c.2317G > T missense
      mutation in the COL1A1 gene, which leads to p.Gly773Cys transversion in the
      triple helical domain of the collagen type I alpha chain. The presence of the
      missense mutation was confirmed with the Sanger sequencing. CONCLUSIONS: Hereby,
      we report a novel mutation in the COL1A1 gene causing severe, life threatening OI
      and indicate the role of de novo mutation in the pathogenesis of rare familial
      diseases. Our study underlines the importance of exome sequencing in disease gene
      discovery for families where conventional genetic testing does not give
      conclusive evidence.

PMID- 25958001
TI  - Surgical treatment of lumbosacral tuberculosis by one-stage debridement and
      anterior instrumentation with allograft through an extraperitoneal anterior
      approach.
AB  - BACKGROUND: This study was aimed to investigate the clinical outcome of
      lumbosacral tuberculosis treatment by one-stage radical debridement with bone
      allograft reconstruction and anterior instrumentation via a retroperitoneal
      approach. METHODS: We retrospectively analyzed a series of 43 patients with
      lumbosacral tuberculosis in whom the lumbosacral junction was exposed via an
      anterior midline retroperitoneal approach. After radical debridement, two
      parallel tricortical iliac crest bone allografts were placed to reconstruct the
      anterior column, and then anterior fixation was performed. RESULTS: The mean
      follow-up period was 34 months (range, 24-91 months), during which no obvious
      loss of correction was observed. No case experienced recurrence, tuberculous
      peritonitis, erectile dysfunction, or retrograde ejaculation. CONCLUSIONS: The
      midline retroperitoneal approach provides direct and safe access to lesions of
      lumbosacral tuberculosis. Two parallel structural iliac crest allografts and
      anterior instrumentation effectively stabilize the lumbosacral junction.

PMID- 25958002
TI  - A bibliometric analysis of malaria research in China during 2004-2014.
AB  - BACKGROUND: China has made great progress in malaria prevention and control, but
      there has been no research to provide a macroscopic overview of malaria research
      in China. This bibliometric analysis was conducted from international databases
      to explore the characteristics of malaria investigations in China. METHODS:
      Published scientific papers about malaria were retrieved from China National
      Knowledge Infrastructure (CNKI), Wanfang database, Cqvip and PubMed during 2004
      2014. Year of publication, first-author affiliation, journal name and keywords
      were extracted with the Bibliographic Items Co-occurrence Matrix Builder
      (BICOMB). High-frequency keywords were selected to construct the co-word matrix
      and divided into eight categories. Sub-networks were utilized to analyse the
      complex knowledge structures. RESULTS: In recent ten years, a total of 5,126
      entries were included. The number of papers on malaria started to increase since
      2010. The papers published by top 12 Chinese journals in the field of malaria
      accounted for 32.98% in overall articles. Most of the studies were conducted by
      the researchers from the Centers for Disease Control and Prevention (CDCs). The
      words "malaria", "imported malaria", "falciparum malaria", "vivax malaria" and
      "malaria surveillance" were the centers of knowledge structures. CONCLUSION:
      Chinese studies on malaria mainly focus on the epidemiology and biomedical
      fields, this study offers a systematic evaluation on the output of malaria
      studies and the elimination of malaria in China.

PMID- 25958004
TI  - Transcultural validation of the SIGAM mobility grades in French: The SIGAM-Fr.
AB  - BACKGROUND: The main French language scales evaluating functioning after lower
      limb amputation have not undergone exhaustive psychometric validation. OBJECTIVE:
      A transcultural validation of the Special Interest Group in Amputee Medicine
      (SIGAM) mobility grades questionnaire, with 21 closed questions, as an
      administered questionnaire. METHODS: The questionnaire translation, back
      translation and original-author validation was followed by a pretest with 5
      patients to check comprehension. The psychometric properties of the scale were
      validated with 49 patients at the definitive prosthesis stage by an investigator
      via telephone. Criterion validity was evaluated by comparison with the Houghton
      Scale score and construct validity by correlation between the questionnaire
      scores and convergent dimensions (performing everyday activities and performing
      transfers on a numerical rating scale [NRS], 2-min walk test) and divergent
      dimensions (managing medication and stump skin care on an NRS). Internal
      consistency was assessed by the Kuder-Richardson Formula 20 (KR-20) coefficient
      and test-retest reproducibility by the Cohen kappa coefficient. RESULTS: The
      resulting questionnaire was validated by the original author after the back
      translation. It showed good psychometric properties when administered by an
      investigator as a self-reporting questionnaire, excellent criterion validity
      (r=0.89, P<0.01), excellent reproducibility (kappa coefficient 0.87) and
      satisfactory construct validity. The KR-20 coefficient was 0.67. CONCLUSION: The
      French version of the SIGAM mobility grades questionnaire (SIGAM-Fr) has
      satisfactory psychometric properties and can be administered in clinical
      practice.

PMID- 25958005
TI  - Reliability and concurrent validity of the Acti'MET calculator: A new tool to
      assess physical activity in cardiac rehabilitation.
AB  - OBJECTIVE: We created a tool for assessing physical activity (PA), the Acti'MET
      calculator, to quickly estimate weekly energy expenditure. This study aimed to
      assess the metrological properties of the tool in cardiac rehabilitation (CR).
      METHODS: Two examiners evaluated the reliability and concurrent validity of the
      tool with cardiac patients. The validity of the tool was assessed by comparison
      with other classical methods for measurement of PA such as the Dijon Physical
      Activity Score (PAS) and the International Physical Activity Questionnaire (IPAQ)
      score, the 6-min walk test (6MWT) and the cardiopulmonary maximal exercise test.
      Correlation was assessed by Pearson or Spearman correlation analysis. RESULTS:
      For the 36 cardiac patients (mean age 55+/-11 years, 24 men), inter-rater and
      intra-rater reliabilities were strong: r=0.87 and r=0.98, respectively, both
      P<0.0001. We found a strong correlation of the Acti'MET score with the IPAQ score
      (r=0.88, P<0.0001), moderate correlation with the PAS (r=0.39, P<0.05) and 6MWT
      (r=0.54, P<0.01), and no correlation with peak power output. CONCLUSION: The
      Acti'MET calculator is reliable, valid and easy to use for assessing PA in CR.
      This tool seems to well reflect the weekly PA, unlike the PAS, which evaluates PA
      on a yearly basis.

PMID- 25958003
TI  - Evaluating the effects of protective ventilation on organ-specific cytokine
      production in porcine experimental postoperative sepsis.
AB  - BACKGROUND: Protective ventilation with lower tidal volume (VT) and higher
      positive end-expiratory pressure (PEEP) reduces the negative additive effects of
      mechanical ventilation during systemic inflammatory response syndrome. We
      hypothesised that protective ventilation during surgery would affect the organ
      specific immune response in an experimental animal model of endotoxin-induced
      sepsis-like syndrome. METHODS: 30 pigs were laparotomised for 2 hours (h), after
      which a continuous endotoxin infusion was started at 0.25 micrograms * kg(-1) *
      h(-1) for 5 h. Catheters were placed in the carotid artery, hepatic vein, portal
      vein and jugular bulb. Animals were randomised to two protective ventilation
      groups (n = 10 each): one group was ventilated with VT 6 mL * kg(-1) during the
      whole experiment while the other group was ventilated during the surgical phase
      with VT of 10 mL * kg(-1). In both groups PEEP was 5 cmH2O during surgery and
      increased to 10 cmH2O at the start of endotoxin infusion. A control group (n =
      10) was ventilated with VT of 10 mL * kg(-1) and PEEP 5 cm H20 throughout the
      experiment. In four sample locations we a) simultaneously compared cytokine
      levels, b) studied the effect of protective ventilation initiated before and
      during endotoxemia and c) evaluated protective ventilation on organ-specific
      cytokine levels. RESULTS: TNF-alpha levels were highest in the hepatic vein, IL-6
      levels highest in the artery and jugular bulb and IL-10 levels lowest in the
      artery. Protective ventilation initiated before and during endotoxemia did not
      differ in organ-specific cytokine levels. Protective ventilation led to lower
      levels of TNF-alpha in the hepatic vein compared with the control group, whereas
      no significant differences were seen in the artery, portal vein or jugular bulb.
      CONCLUSIONS: Variation between organs in cytokine output was observed during
      experimental sepsis. We see no implication from cytokine levels for initiating
      protective ventilation before endotoxemia. However, during endotoxemia protective
      ventilation attenuates hepatic inflammatory cytokine output contributing to a
      reduced total inflammatory burden.

PMID- 25958006
TI  - Comment on "Piriformis muscle syndrome: Diagnostic criteria and treatment of a
      monocentric series of 250 patients" by F. Michel et al. Ann Phys Rehabil Med
      2013;56:371-83.

PMID- 25958008
TI  - Product in indole detection by Ehrlich's reagent.
AB  - Ehrlich's reagent (p-dimethylaminobenzaldehyde [DMAB, 1] in 95% EtOH with HCl as
      catalyst) was employed in spot tests of indoles, providing a diagnosis of, for
      example, liver diseases, hemolytic processes, occlusion of the common bile duct,
      and carcinoid syndrome. Although the reagent has been widely used for more than a
      century, it is not clear how many indole molecules react with a DMAB molecule and
      whether the reaction takes place at the alpha- or beta-position of the indole
      molecule. Research here shows that the reaction of DMAB (1) with indole (2) in a
      1:2 ratio gives beta-bis(indolyl)methane (3). The reaction occurs at the beta
      position of indole under the conditions of the Ehrlich test, as confirmed by the
      crystal structure of 3. 

PMID- 25958007
TI  - Aortoenteric fistula.
AB  - Aortoenteric fistula is a rare clinical entity. Early clinical and imaging
      diagnosis and prompt surgical intervention are crucial for patient survival. We
      present a case of aortoenteric fistula with direct contrast extravasation from
      the abdominal aorta into an ileal loop during Multi-Detector Computed Tomography
      scan. 

PMID- 25958009
TI  - Diagnostic and Therapeutic Management of Chronic Urticaria by Dermatologists and
      the Role of Dermatology Departments.

PMID- 25958010
TI  - Prediction of cytochrome P450 mediated metabolism.
AB  - Cytochrome P450 enzymes (CYPs) form one of the most important enzyme families
      involved in the metabolism of xenobiotics. CYPs comprise many isoforms, which
      catalyze a wide variety of reactions, and potentially, a large number of
      different metabolites can be formed. However, it is often hard to rationalize
      what metabolites these enzymes generate. In recent years, many different in
      silico approaches have been developed to predict binding or regioselective
      product formation for the different CYP isoforms. These comprise ligand-based
      methods that are trained on experimental CYP data and structure-based methods
      that consider how the substrate is oriented in the active site or/and how
      reactive the part of the substrate that is accessible to the heme group is. We
      will review key aspects for various approaches that are available to predict
      binding and site of metabolism (SOM), what outcome can be expected from the
      predictions, and how they could potentially be improved. 

PMID- 25958012
TI  - Response to comments on: Maleszewski JJ et al. IgG4-related disease of the aortic
      valve: a report of two cases and review of the literature. Cardiovasc Pathol
      2015;24(1)56-9.

PMID- 25958013
TI  - Extracellular vesicle microRNA transfer in cardiovascular disease.
AB  - microRNAs (miRNAs) are a class of small regulatory RNAs that decrease protein
      translation to fine-tune cellular function. Recently, miRNAs were found to
      transfer from a donor cell into a recipient cell via exosomes and microparticles.
      These microvesicles are found in blood, urine, saliva, and other fluid
      compartments. miRNAs are delivered with intact functionality and have been
      repeatedly shown to regulate protein expression in recipient cells in a paracrine
      fashion. Thus, transported miRNAs are a new class of cell-to-cell regulatory
      species. Exosomal miRNA transfer is now being reported in cardiovascular systems
      and disease. In the blood vessels, this transfer modulates atherosclerosis and
      angiogenesis. In the heart, it modulates heart failure, myocardial infarction,
      and response to ischemic preconditioning. This review describes our current
      understanding of extracellular vesicle miRNA transfer, demonstrating the roles of
      miR-126, miR-146a, miR-143, and other miRNAs being shuttled from endothelial
      cells, stem cells, fibroblasts and others into myocytes, endothelial cells, and
      smooth muscle cells to activate cellular changes and modulate disease phenotypes.

PMID- 25958014
TI  - Characterization of myocardial T1-mapping bias caused by intramyocardial fat in
      inversion recovery and saturation recovery techniques.
AB  - BACKGROUND: Quantitative measurement of T1 in the myocardium may be used to
      detect both focal and diffuse disease processes such as interstitial fibrosis or
      edema. A partial volume problem exists when a voxel in the myocardium also
      contains fat. Partial volume with fat occurs at tissue boundaries or within the
      myocardium in the case of lipomatous metaplasia of replacement fibrosis, which is
      commonly seen in chronic myocardial infarction. The presence of fat leads to a
      bias in T1 measurement. The mechanism for this artifact for widely used T1
      mapping protocols using balanced steady state free precession readout and the
      dependence on off-resonance frequency are described in this paper. METHODS:
      Simulations were performed to illustrate the behavior of mono-exponential fitting
      to bi-exponential mixtures of myocardium and fat with varying fat fractions. Both
      inversion recovery and saturation recovery imaging protocols using balanced
      steady state free precession are considered. In-vivo imaging with T1-mapping,
      water/fat separated imaging, and late enhancement imaging was performed on
      subjects with chronic myocardial infarction. RESULTS: In n = 17 subjects with
      chronic myocardial infarction, lipomatous metaplasia is evident in 8 patients
      (47%). Fat fractions as low as 5% caused approximately 6% T1 elevation for the
      out-of-phase condition, and approximately 5% reduction of T1 for the in-phase
      condition. T1 bias in excess of 1000 ms was observed in lipomatous metaplasia
      with fat fraction of 38% in close agreement with simulation of the specific
      imaging protocols. CONCLUSIONS: Measurement of the myocardial T1 by widely used
      balanced steady state free precession mapping methods is subject to bias when
      there is a mixture of water and fat in the myocardium. Intramyocardial fat is
      frequently present in myocardial scar tissue due lipomatous metaplasia, a process
      affecting myocardial infarction and some non-ischemic cardiomyopathies. In cases
      of lipomatous metaplasia, the T1 biases will be additive or subtractive depending
      on whether the center frequency corresponds to the myocardium and fat being in
      phase or out-of-phase, respectively. It is important to understand this
      mechanism, which may otherwise lead to erroneous interpretation.

PMID- 25958011
TI  - Pre-treatment effects of peripheral tumors on brain and behavior:
      neuroinflammatory mechanisms in humans and rodents.
AB  - Cancer patients suffer high levels of affective and cognitive disturbances, which
      have been attributed to diagnosis-related distress, impairment of quality of
      life, and side effects of primary treatment. An inflammatory microenvironment is
      also a feature of the vast majority of solid tumors. However, the ability of
      tumor-associated biological processes to affect the central nervous system (CNS)
      has only recently been explored in the context of symptoms of depression and
      cognitive disturbances. In this review, we summarize the burgeoning evidence from
      rodent cancer models that solid tumors alter neurobiological pathways and
      subsequent behavioral processes with relevance to affective and cognitive
      disturbances reported in human cancer populations. We consider, in parallel, the
      evidence from human clinical cancer research demonstrating that affective and
      cognitive disturbances are common in some malignancies prior to diagnosis and
      treatment. We further consider the underlying neurobiological pathways, including
      altered neuroinflammation, tryptophan metabolism, prostaglandin synthesis and
      associated neuroanatomical changes, that are most strongly implicated in the
      rodent literature and supported by analogous evidence from human cancer
      populations. We focus on the implications of these findings for behavioral
      researchers and clinicians, with particular emphasis on methodological issues and
      areas of future research. 

PMID- 25958015
TI  - Is the Guideline Process Replicable and, if Not, What Does This Mean?
AB  - Increasingly, guidelines determine how medical care will be provided. However
      there has been limited study of the determinants of the reliability of the
      guideline process. Guidelines translate evidence into recommendations. If only
      the evidence determines the recommendations, given the same evidence, different
      panels of experts should make the same recommendations. That is, the process
      should be replicable, an essential characteristic of a valid scientific process.
      The multiple recent cholesterol guidelines, which have considered the same
      evidence, offer an opportunity to examine guidelines from this perspective.
      Considerable discordance among the guideline recommendations is evident pointing
      to an important role for the participants, in addition to the evidence, in the
      development of guideline recommendations. Guideline recommendations, therefore,
      appear to be based on both evidence and expert opinion. 

PMID- 25958016
TI  - Understanding and Improving Cardiovascular Health: An Update on the American
      Heart Association's Concept of Cardiovascular Health.
AB  - The American Heart Association's 2020 Strategic Impact Goal is "By 2020, to
      improve the cardiovascular health of all Americans by 20% while reducing deaths
      from cardiovascular diseases and stroke by 20%." To monitor progress towards this
      goal, a new construct "ideal cardiovascular health" (iCVH) was defined that
      includes the simultaneous presence of optimal levels of seven health behaviors
      (physical activity, smoking, dietary intake, and body mass index) and factors
      (total cholesterol, blood pressure and fasting blood glucose). In this review, we
      present a summary of major concepts related to the concept of iCVH and an update
      of the literature in this area since publication of the 2020 Strategic Impact
      Goal, including trends in iCVH prevalence, new determinants and outcomes related
      to iCVH, strategies for maintaining or improving iCVH, policy implications of the
      iCVH model, and the remaining challenges to reaching the 2020 Strategic Impact
      Goal. 

PMID- 25958017
TI  - 5,6-delta-DHTL, a stable metabolite of arachidonic acid, is a potential substrate
      for paraoxonase 1.
AB  - Paraoxonase 1 (PON1) is an antiatherogenic high density lipoprotein-associated
      lactonase. Recent findings revealed that PON1 knockout mice have low blood
      pressure, which is negatively correlated with the level of 5,6
      epoxyeicosatrienoic acid (5,6-EET), a cytochrome P450 -derived arachidonic acid
      metabolite. 5,6-EET is an endothelium-derived hyperpolarizing factor that causes
      arterial dilation. Under physiological conditions, 5,6-EET is unstable,
      transforming to its delta-lactone (5,6-delta-DHTL) that evades the degradation by
      soluble epoxide hydrolase (sEH), arguing for the existence of yet another enzyme
      that is responsible specifically for its hydrolysis. We therefore hypothesized
      that PON1 degrades the 5,6-delta-DHTL, and this specific PON1 lactonase activity
      thus decreases endothelial vasodilatation. The aim of the present study was to
      investigate the PON1-5,6-delta-DHTL relationship. A liquid chromatography mass
      spectrometry based method for 5,6-EET derivatives identification was developed.
      Tracking the lactonization of 5,6-EET in a physiological solution revealed that
      5,6-EET was fully converted into 5,6-delta-DHTL. Incubation of 5,6-delta-DHTL
      with rePON1 resulted in 85.1+/-3.4% degradation of the substrate to 5,6
      dihydroxytrienoic acid (5,6-DHET), while only 12.0+/-8.7% hydrolysis was detected
      in the absence of PON1. Accordingly, the levels of 5,6-DHTL were found to be
      significantly higher in the PON1KO mice than in the wild type mice. Kinetic
      analysis revealed values of Vmax=0.021+/-0.01MUM/s and Km=150.99+/-62.1MUM.
      Calculation of the docking energy suggested possible interaction of the 5,6-delta
      DHTL in the catalytic region of PON1 with free energy of-5.57 Kcal/mol,
      preferentially for the (S) enantiomer. These findings demonstrate that 5,6-delta
      DHTL is a PON1 substrate and imply that the 5,6-EET vasodilation effect may be
      impaired by PON1. 

PMID- 25958018
TI  - Adult-gerontology clinical nurse specialists: The time is now.

PMID- 25958020
TI  - Re: Prophylactic Sildenafil Citrate Improves Select Aspects of Sexual Function in
      Men Treated with Radiotherapy for Prostate Cancer: M. J. Zelefsky, D. Shasha, R.
      D. Branco, M. Kollmeier, R. E. Baser, X. Pei, R. Ennis, R. Stock, N. Bar-Chama
      and J. P. Mulhall J Urol 2014; 192: 868-874.

PMID- 25958019
TI  - Re: A Randomized Controlled Study of the Efficacy of Tamsulosin Monotherapy and
      its Combination with Mirabegron for Overactive Bladder Induced by Benign
      Prostatic Obstruction: K. Ichihara, N. Masumori, F. Fukuta, T. Tsukamoto, A.
      Iwasawa and Y. Tanaka J Urol 2015; 193: 921-926.

PMID- 25958021
TI  - Re: Overuse of Antimicrobial Prophylaxis in Community Practice Urology: M.
      Mossanen, J. K. Calvert, S. K. Holt, A. C. James, J. L. Wright, J. D. Harper, J.
      N. Krieger and J. L. Gore J Urol 2015; 193: 543-547.

PMID- 25958022
TI  - Reply by Authors.

PMID- 25958023
TI  - Reply by Authors.

PMID- 25958024
TI  - Re: Combined Chemoradiation as Primary Treatment for Invasive Male Urethral
      Cancer: M. Kent, L. Zinman, L. Girshovich, J. Sands and A. Vanni J Urol
      2015;193:532-537.

PMID- 25958025
TI  - Reply by Authors.

PMID- 25958026
TI  - [Suitability of autologous blood donation before bone marrow donation].
AB  - We assessed the benefit of predeposite autologous blood donation (PAD) before
      bone marrow (BM) donation on transfusion requirements, haemoglobin concentrations
      (Hb) and the occurrence of adverse events (AE). We collected data retrospectively
      from 50 donors of BM with PAD from 2010 to 2014. An autologous transfusion (AT)
      was given to 50% of the donors (group 1). In the group 2, the products from PAD
      were not used. The total volume median of marrow harvested was 17.7 mL/k (range
      12.3-21.4) in the group 1 and 13.3 mL/k (8.6-22.6) in the group 2. The female
      ratio was higher in the group 1 (60%) than in the group 2 (16%). Bone marrow
      harvest led to a decline in Hb (from PAD to first day after BM donation) by 2.9
      g/dL (1.5-5.5) in the group 1 and by 3.5 g/dL (1.2-5) in the group 2. The post
      harvest Hb (D+1) median was identical in the two groups: 10.9 g/dL (7.6-13.5) in
      the group 1 versus 11.5 g/dL (9.3-13.4) in the group 2. Six AE were reported in
      each group. In the group with AE, the median weight was lower: 58 k (50-71)
      versus 75 k (52-110); and the median total volume of marrow harvested was higher:
      20.1 mL/k (9.9-21.4) versus 14.3 mL/k (8.6-22.6). All post-harvest Hb were >=
      7.6g/dL. This study shows the high loss of Hb after BM donation but not enough to
      prove a blood transfusion in BM donors with median age of 36 years (16-62) and
      without comorbidity. The occurrence of AE (25% of BM donors) justifies a careful
      surveillance after the BM donation. The PAD should not be routinely offered to
      bone marrow donors.

PMID- 25958027
TI  - Multiscale properties of weighted total variation flow with applications to
      denoising and registration.
AB  - Images consist of structures of varying scales: large scale structures such as
      flat regions, and small scale structures such as noise, textures, and rapidly
      oscillatory patterns. In the hierarchical (BV, L(2)) image decomposition, Tadmor,
      et al. (2004) start with extracting coarse scale structures from a given image,
      and successively extract finer structures from the residuals in each step of the
      iterative decomposition. We propose to begin instead by extracting the finest
      structures from the given image and then proceed to extract increasingly coarser
      structures. In most images, noise could be considered as a fine scale structure.
      Thus, starting the image decomposition with finer scales, rather than large
      scales, leads to fast denoising. We note that our approach turns out to be
      equivalent to the nonstationary regularization in Scherzer and Weickert (2000).
      The continuous limit of this procedure leads to a time-scaled version of total
      variation flow. Motivated by specific clinical applications, we introduce an
      image depending weight in the regularization functional, and study the
      corresponding weighted TV flow. We show that the edge-preserving property of the
      multiscale representation of an input image obtained with the weighted TV flow
      can be enhanced and localized by appropriate choice of the weight. We use this in
      developing an efficient and edge-preserving denoising algorithm with control on
      speed and localization properties. We examine analytical properties of the
      weighted TV flow that give precise information about the denoising speed and the
      rate of change of energy of the images. An additional contribution of the paper
      is to use the images obtained at different scales for robust multiscale
      registration. We show that the inherently multiscale nature of the weighted TV
      flow improved performance for registration of noisy cardiac MRI images, compared
      to other methods such as bilateral or Gaussian filtering. A clinical application
      of the multiscale registration algorithm is also demonstrated for aligning
      viability assessment magnetic resonance (MR) images from 8 patients with previous
      myocardial infarctions.

PMID- 25958028
TI  - Globally optimal co-segmentation of three-dimensional pulmonary 1H and
      hyperpolarized 3He MRI with spatial consistence prior.
AB  - Pulmonary imaging using hyperpolarized (3)He/(129)Xe gas is emerging as a new way
      to understand the regional nature of pulmonary ventilation abnormalities in
      obstructive lung diseases. However, the quantitative information derived is
      completely dependent on robust methods to segment both functional and
      structural/anatomical data. Here, we propose an approach to jointly segment the
      lung cavity from (1)H and (3)He pulmonary magnetic resonance images (MRI) by
      constraining the spatial consistency of the two segmentation regions, which
      simultaneously employs the image features from both modalities. We formulated the
      proposed co-segmentation problem as a coupled continuous min-cut model and showed
      that this combinatorial optimization problem can be solved globally and exactly
      by means of convex relaxation. In particular, we introduced a dual coupled
      continuous max-flow model to study the convex relaxed coupled continuous min-cut
      model under a primal and dual perspective. This gave rise to an efficient duality
      based convex optimization algorithm. We implemented the proposed algorithm in
      parallel using general-purpose programming on graphics processing unit (GPGPU),
      which substantially increased its computational efficiency. Our experiments
      explored a clinical dataset of 25 subjects with chronic obstructive pulmonary
      disease (COPD) across a wide range of disease severity. The results showed that
      the proposed co-segmentation approach yielded superior performance compared to
      single-channel image segmentation in terms of precision, accuracy and robustness.

PMID- 25958029
TI  - Cloning, characterization and cadmium inducibility of metallothionein in the
      testes of the mudskipper Boleophthalmus pectinirostris.
AB  - Metallothioneins (MTs) are cysteine-rich, low molecular weight, and heavy metal
      binding protein molecules. MT participates in metallic homeostasis and
      detoxification in living animals due to its abundant cysteine. In order to
      investigate the functions of MT during spermiogenesis in the mudskipper
      (Boleophthalmus pectinirostris), we identified the MT complete which contains: an
      83bp 5' untranslated region, a 110bp 3' untranslated region, and a 183bp open
      reading frame. The protein alignment between MT sequences of other species shows
      a high similarity and a strong identity in cysteine residues vital for the metal
      binding affinity of MT. The localizations of MT were mainly in the cytoplasm of
      germinal cells, indicating a role in spermatogenesis and testis protection. After
      the cadmium (Cd) exposure, the testis presents abnormal morphology and MT mRNA
      expression, both of which indicate a sensitive response of testis MT to Cd.
      Therefore, we suggest that MTs play an important role in spermatogenesis and
      testes protection against Cd toxicity in B. pectinirostris. 

PMID- 25958030
TI  - Regulation of body metal concentrations: Toxicokinetics of cadmium and zinc in
      crickets.
AB  - Previous studies indicated that essential and xenobiotic metals differ
      substantially in terms of their toxicokinetics. Whether these differences are due
      to different assimilation rates, different elimination rates, or both, and
      whether all metals are regulated in a similar manner but with different
      efficiency remains unclear. To compare the mechanisms responsible for the
      regulation of different metals, parameters for toxicokinetic models have to be
      tested under exposures to the identical molar concentration of those metals. In
      this study, the cricket Gryllus assimilis was exposed to Zn or Cd at 2.5, 10, and
      40mMkg(-1) dry food. The body concentrations of the metals were not perfectly
      regulated by the crickets. For Zn, a clear increase in the body concentration was
      found only at the highest treatment; whereas at the lowest treatment, the
      internal concentration remained unchanged throughout the experiment. At the
      lowest Zn concentration, the assimilation (kA) [day(-1)] and elimination (kE)
      [day(-1)] rate constants were balanced (kA=0.024, kE=0.024). When increasing the
      Zn exposure, kA decreased to 0.018 at 10mMkg(-1) and 0.01 at 40mMkg(-1), and kE
      increased to 0.05 and 0.07, respectively. Therefore, the body concentration of Zn
      was regulated by simultaneously changing the assimilation and elimination rate.
      By contrast, even at the lowest treatment, a significant increase in Cd
      concentration was observed in the crickets. The equilibrium Cd concentration
      resulted almost exclusively from increasing kE from 0.17, through 0.28 to 0.61 at
      2.5, 10 and 40mMkg(-1). The kA for Cd did not reveal any clear trend. Zn was more
      efficiently regulated by crickets than was Cd: a 16-fold increase in exposure
      concentration (from 2.5 to 40mM Znkg(-1)) resulted only in a twofold increase of
      internal concentration, whereas the identical increase in Cd exposure
      concentration resulted in almost a sevenfold increase in internal concentration
      of this metal. 

PMID- 25958031
TI  - Predictive value of specific ultrasound findings when used as a screening test
      for abnormalities on VCUG.
AB  - BACKGROUND: Renal and bladder ultrasound (RBUS) is often used as an initial
      screening test for children after urinary tract infection (UTI), and the 2011 AAP
      guidelines specifically recommend RBUS be performed first, with voiding
      cystourethrogram (VCUG) to be performed only if the ultrasound is abnormal. It is
      uncertain whether specific RBUS findings, alone or in combination, might make
      RBUS more useful as a predictor of VCUG abnormalities. AIMS: To evaluate the
      association of specific RBUS with VCUG findings, and determine whether predictive
      models that accurately predict patients at high risk of VCUG abnormalities, based
      on RBUS findings, can be constructed. METHODS: and study sample: A total of 3995
      patients were identified with VCUG and RBUS performed on the same day. The RBUS
      and VCUG reports were reviewed and the findings were classified. Analysis was
      limited to patients aged 0-60 months with no prior postnatal genitourinary
      imaging and no history of prenatal hydronephrosis. ANALYSIS: The associations
      between large numbers of specific RBUS findings with abnormalities seen on VCUG
      were investigated. Both multivariate logistic models and a neural network machine
      learning algorithms were constructed to evaluate the predictive power of RBUS for
      VCUG abnormalities (including VUR or bladder/urethral findings). Sensitivity,
      specificity, predictive values and area under receiving operating curves (AUROC)
      of RBUS for VCUG abnormalities were determined. RESULTS: A total of 2259 patients
      with UTI as the indication for imaging were identified. The RBUS was reported as
      "normal" in 75.0%. On VCUG, any VUR was identified in 41.7%, VUR grade > II in
      20.9%, and VUR grade > III in 2.8%. Many individual RBUS findings were
      significantly associated with VUR on VCUG. Despite these strong univariate
      associations, multivariate modeling didn't result in a predictive model that was
      highly accurate. Multivariate logistic regression built via stepwise selection
      had: AUROC = 0.57, sensitivity = 86% and specificity = 25% for any VUR; AUROC =
      0.60, sensitivity = 5% and specificity = 99% for VUR grade > II; and AUROC =
      0.67, sensitivity = 6% and specificity = 99% for VUR grade > III. The best
      predictive model constructed via neural networks had: AUROC = 0.69, sensitivity =
      64% and specificity = 60% for any VUR; AUROC = 0.67, sensitivity = 18% and
      specificity = 98% for VUR grade > II; and AUROC = 0.79, sensitivity = 32% and
      specificity = 100% for VUR grade > III. CONCLUSIONS: Even with the state-of-the
      art predictive models, abnormal findings on RBUS provide a poor screening test
      for genitourinary abnormalities. Renal bladder ultrasound and VCUG should be
      considered complementary, as they provide important, but different, information.

PMID- 25958032
TI  - Selective glucocorticoid receptor modulation: New directions with non-steroidal
      scaffolds.
AB  - Glucocorticoids remain the frontline treatment for inflammatory disorders, yet
      represent a double-edged sword with beneficial therapeutic actions alongside
      adverse effects, mainly in metabolic regulation. Considerable efforts were made
      to improve this balance by attempting to amplify therapeutic beneficial anti
      inflammatory actions and to minimize adverse metabolic actions. Most attention
      has focused on the development of novel compounds favoring the transrepressing
      actions of the glucocorticoid receptor, assumed to be important for anti
      inflammatory actions, over the transactivating actions, assumed to underpin the
      undesirable actions. These compounds are classified as selective glucocorticoid
      receptor agonists (SEGRAs) or selective glucocorticoid receptor modulators
      (SEGRMs). The latter class is able to modulate the activity of a GR agonist
      and/or may not classically bind the glucocorticoid receptor ligand-binding
      pocket. SEGRAs and SEGRMs are collectively denominated SEGRAMs (selective
      glucocorticoid receptor agonists and modulators). Although this transrepression
      vs transactivation concept proved to be too simplistic, the developed SEGRAMs
      were helpful in elucidating various molecular actions of the glucocorticoid
      receptor, but have also raised many novel questions. We discuss lessons learned
      from recent mechanistic studies of selective glucocorticoid receptor modulators.
      This is approached by analyzing recent experimental insights in comparison with
      knowledge obtained using mutant GR research, thus clarifying the current view on
      the SEGRAM field. These insights also contribute to our understanding of the
      processes controlling glucocorticoid-mediated side effects as well as
      glucocorticoid resistance. Our perspective on non-steroidal SEGRAs and SEGRMs
      considers remaining opportunities to address research gaps in order to harness
      the potential for more safe and effective glucocorticoid receptor therapies. 

PMID- 25958033
TI  - Utility of Reviewing Radiology Studies in Electronic Medical Records When
      Preparing Bone Mineral Density Reports.
AB  - We quantitated how often review of recent radiology studies provides information
      useful to the densitometrist. While preparing bone mineral density (BMD) reports
      on 1012 consecutive patients, radiology reports in electronic medical records
      (EMRs) for the previous 5 years at potentially relevant sites (lumbar spine X
      rays, abdominal computed tomography (CT) scans, and so forth) were reviewed. When
      a study was found, it received a grade according to how relevant findings were to
      the BMD report: "1" for studies that were irrelevant, "2" for those that
      confirmed the impression formed from review of the BMD images, "3" for those that
      clarified the impression that was unclear after reviewing the BMD images, and "4"
      for those that revealed new relevant data when no abnormality was noted on review
      of the BMD images. A total of 562 patients (55.5%) had a radiologic study at a
      site of potential interest within the past 5 years. Fifty-three patients (5.2% of
      all patients) had a grade 4 study, 88 patients (8.7% of all patients) had a grade
      3 study, and 185 patients (18.3% of all patients) had a grade 2 study. Two
      hundred sixty-four patients (25.8%) had a grade 2 or 3 study, and 299 (29.5%) had
      a grade 2-4 study. The radiographic study that was most likely to be found in
      patients' EMR was chest X-ray (34.7% of all patients), but it was also the one
      that was least likely to have any relevance to the reader; only 10.5% of the
      total chest X-rays were graded 2-4. The next most likely studies to be found in
      patients' EMR were abdominal CT scans (18.0% of all patients) and lumbar spine X
      rays (14.4% of all patients), but these studies were much more likely to be
      useful to the reader, as 62.6% of abdominal CT scans and 78.1% of lumbar spine X
      rays were graded 2-4. The likelihood of a patient having radiologic examinations
      in the EMR at sites potentially relevant to the BMD reader is high, but the
      likelihood that these clarify abnormalities noted on BMD is only moderate. Review
      of the EMR is unlikely to be relevant when the dual-energy X-ray absorptiometry
      images are normal. 

PMID- 25958034
TI  - Scanning electron microscopic analysis of pancreatic tissue in alcoholic and
      tropical chronic pancreatitis.
AB  - INTRODUCTION: Chronic Pancreatitis (CP) is a heterogenous disease with alcoholic
      chronic pancreatitis (ACP) dominating in the West, and idiopathic or tropical
      chronic pancreatitis (TCP) in the tropics. The aim of this study is to assess the
      feasibility of using a scanning electron microscope (SEM) to analyze the ultra
      structural changes in alcoholic and tropical subtypes of CP. METHODS: Chronic
      pancreatitis tissue samples were taken from the biopsy samples of 16 patients
      (seven ACP and nine TCP) who underwent drainage procedures for CP. These samples
      were subjected to SEM analysis and findings of normal pancreas were compared with
      those of CP for appreciating differences in their architectural changes. RESULTS:
      Normal architecture of pancreas could be observed as lobules of parenchyma,
      ductal system and definite loci of Islets of Langerhans (IOL). CP samples showed
      loss of architecture in the form of severe fibrosis and calcifications. In ACP,
      the fibrosis was predominantly seen towards the periphery of the gland sparing
      the periductal areas. These fibres were strangulating and damaging the
      parenchyma. Crystals were seen over these fibres. In TCP, fibrosis was moderate
      and uniform throughout the parenchyma. Moreover the crystals were larger and
      intraluminal. Total fatty replacement of parenchyma was a striking feature in
      TCP, seen exclusively in diabetics with gross atrophy of IOL. CONCLUSION: SEM
      gives the real-life pictures of fibrosis, fatty change, ductal changes,
      calcifications and thus the actual extent of damage in CP better than the
      ordinary light microscopy.

PMID- 25958035
TI  - Temporal and spatial patterns of suicides in Stockholm's subway stations.
AB  - This paper investigates the potential temporal and spatial variations of suicides
      in subway stations in Stockholm, Sweden. The study also assesses whether the
      variation in suicide rates is related to the station environments by controlling
      for each station's location and a number of contextual factors using regression
      models and geographical information systems (GIS). Data on accidents are used as
      references for the analysis of suicides. Findings show that suicides tend to
      occur during the day and in the spring. They are concentrated in the main
      transportation hubs but, interestingly, during off-peak hours. However, the
      highest rates of suicides per passenger are found in Stockholm's subway stations
      located in the Southern outskirts. More than half of the variation in suicide
      rates is associated with stations that have walls between the two sides of the
      platform but still allow some visibility from passers-by. The surrounding
      environment and socioeconomic context show little effect on suicide rates, but
      stations embedded in areas with high drug-related crime rates tend to show higher
      suicide rates. 

PMID- 25958036
TI  - Old age as risk indicator for poor end-of-life care quality - a population-based
      study of cancer deaths from the Swedish Register of Palliative Care.
AB  - BACKGROUND: If patient age affects the quality of end-of-life care in cancer is
      unknown. Using data from a population-based register of palliative care in
      Sweden, we addressed this question. METHODS: This nation-wide study focused on
      the last week of life of adults dying from cancer in 2011-2012, based on data
      reported to a national quality register for end-of-life care (N=26,976). We
      specifically investigated if age-dependent differences were present with respect
      to thirteen indicators of palliative care quality. Patients were categorised in
      one out of five pre-defined age groups. Odds ratios (OR) with 95% confidence
      intervals (CIs), adjusted for type of end-of-life care unit, were calculated
      using logistic regression, with the oldest group as reference. FINDINGS: Age
      dependent differences in implementation rate were detected for ten out of
      thirteen end-of-life care quality indicators, most of which were progressively
      less well met with each increment in age group. Compared to elderly cancer
      patients, young patients were more often informed about imminent death, (OR, 3.9;
      95% CI 2.5-5.9, p<0.001), were more often systematically assessed for the
      presence and severity of pain (OR, 1.6; 95% CI 1.2-2.1, p<0.001) or other
      symptoms (OR, 1.4; 95% CI 1.0-1.9, p=0.044), were more likely to be assessed by
      palliative care consultation services (OR, 4.3; 95% CI 3.3-5.7, p<0.001) and to
      have injections prescribed as needed against pain (OR, 3.4; 95% CI 1.3-9.4,
      p=0.016), anxiety (OR, 3.8; 95% CI 2.0-7.1, p<0.001) or nausea (OR, 3.6; 95% CI
      2.3-5.7, p<0.001). The families of young patients were more likely to be informed
      about imminent death (OR, 2.6; 95% CI 1.5-4.3, p=0.001) and to be offered
      bereavement support (OR, 4.6; 95% CI 2.7-7.8, p<0.001). INTERPRETATION: Old age
      is a risk indicator for poor end-of-life care quality among cancer patients in
      Sweden. FUNDING: The executive committee of the National Quality Registries in
      Sweden.

PMID- 25958037
TI  - Survivorship after childhood cancer: PanCare: a European Network to promote
      optimal long-term care.
AB  - Survival after childhood cancer has improved substantially over recent decades.
      Although cancer in childhood is rare increasingly effective treatments have led
      to a growing number of long-term survivors. It is estimated that there are
      between 300,000 and 500,000 childhood cancer survivors in Europe. Such good
      survival prospects raise important questions relating to late effects of
      treatment for cancer. Research has shown that the majority will suffer adverse
      health outcomes and premature mortality compared with the general population.
      While chronic health conditions are common among childhood cancer survivors, each
      specific type of late effect is very rare. Long-term effects must be considered
      particularly when addressing complex multimodality treatments, and taking into
      account the interaction between aspects of treatment and genotype. The PanCare
      Network was set up across Europe in order to effectively answer many of these
      questions and thereby improve the care and quality of life of survivors. The need
      for a structured long-term follow-up system after childhood cancer has been
      recognised for some time and strategies for implementation have been developed,
      first nationally and then trans-nationally, across Europe. Since its first
      meeting in Lund in 2008, the goal of the PanCare Network has been to coordinate
      and implement these strategies to ensure that every European survivor of
      childhood and adolescent cancer receives optimal long-term care. This paper will
      outline the structure and work of the PanCare Network, including the results of
      several European surveys, the start of two EU-funded projects and interactions
      with relevant stakeholders and related projects. 

PMID- 25958038
TI  - Comparison of Laparoscopic Myomectomy in Large Myomas With and Without Leuprolide
      Acetate.
AB  - STUDY OBJECTIVE: To evaluate the efficacy of gonadotropin-releasing hormone
      analogue (GnRHa) use before laparoscopic myomectomy (LM) in large myomas. DESIGN:
      Prospective study (Canadian Task Force classification II-1). SETTING: University
      affiliated hospital. PATIENTS: Ninety-one women with large myomas (>=10 cm) or
      more than 2 myomas >= 5 cm underwent LM between July 2011 and March 2014.
      INTERVENTIONS: Forty patients underwent LM after GnRHa use (group A) and 51
      underwent LM only (group B). GnRHa was used for 3 doses every 4 weeks before LM
      in group A. MEASUREMENTS AND MAIN RESULTS: Group A had a significantly smaller
      maximum diameter of the largest myoma than group B (8.5 +/- 2.1 vs 10.7 +/- 2.4,
      p < .001) and fewer patients with myomas larger than 10 cm after GnRHa
      administration (33% vs 67%, p = .001). In group A, there was a decrease in 2 or
      more myomas >= 5 cm (20% vs 50%) after GnRHa use. Group A also had significantly
      smaller mean myoma weight (448 vs 567 g, p = .045) and significantly shorter mean
      operative time (129 +/- 30 vs 152 +/- 34 minutes, p = .001). Most patients in
      group A (40%) had an operative time < 119 minutes, whereas most patients in group
      B (37%) had an operative time between 150 and 179 minutes. Group A also had less
      intraoperative blood loss (84 +/- 53 vs 137 +/- 166 mL, p < .001), drop in
      hemoglobin (1.5 +/- 0.8 vs 3.0 +/- 1.7 g/dl, p < .001), excessive bleeding (5% vs
      33%, p = .001), postoperative hematoma (2.5% vs 9.8%, p = .168), and blood
      transfusion (7.5% vs 35%, p = .001). CONCLUSION: GnRHa before LM in large myomas
      may be an effective adjuvant treatment for women with large and multiple myomas.
      This method is beneficial in decreasing operative time, intraoperative bleeding,
      postoperative hemorrhage, and need of blood transfusion.

PMID- 25958039
TI  - Three-dimensional dose accumulation in pseudo-split-field IMRT and brachytherapy
      for locally advanced cervical cancer.
AB  - PURPOSE: Dose accumulation of split-field external beam radiotherapy (EBRT) and
      brachytherapy (BT) is challenging because of significant EBRT and BT dose
      gradients in the central pelvic region. We developed a method to determine
      biologically effective dose parameters for combined split-field intensity
      modulated radiation therapy (IMRT) and image-guided BT in locally advanced
      cervical cancer. METHODS AND MATERIALS: Thirty-three patients treated with split
      field-IMRT to 45.0-51.2 Gy in 1.6-1.8 Gy per fraction to the elective pelvic
      lymph nodes and to 20 Gy to the central pelvis region were included in this
      study. Patients received six weekly fractions of high-dose rate BT to 6.5-7.3 Gy
      per fraction. A dose tracker software was developed to compute the equivalent
      dose in 2-Gy fractions (EQD2) to gross tumor volume (GTV), organs-at-risk and
      point A. Total dose-volume histogram parameters were computed on the 3D combined
      EQD2 dose based on rigid image registration. The dose accumulation uncertainty
      introduced by organ deformations between IMRT and BT was evaluated. RESULTS:
      According to International Commission on Radiation Unit and Measurement and GEC
      European Society for Therapeutic Radiology and Oncology recommendations, D98,
      D90, D50, and D2cm3 EQD2 dose-volume histogram parameters were computed. GTV D98
      was 84.0 +/- 26.5 Gy and D2cc was 99.6 +/- 13.9 Gy, 67.4 +/- 12.2 Gy, 75.0 +/-
      10.1 Gy, for bladder, rectum, and sigmoid, respectively. The uncertainties
      induced by organ deformation were estimated to be -1 +/- 4 Gy, -3 +/- 5 Gy, 2 +/-
      3 Gy, and -3 +/- 5 Gy for bladder, rectum, sigmoid, and GTV, respectively.
      CONCLUSIONS: It is feasible to perform 3D EQD2 dose accumulation to assess high
      and intermediate dose regions for combined split-field IMRT and BT.

PMID- 25958040
TI  - Calcium-dependent mitochondrial cAMP production enhances aldosterone secretion.
AB  - Glomerulosa cells secrete aldosterone in response to agonists coupled to Ca(2+)
      increases such as angiotensin II and corticotrophin, coupled to a cAMP dependent
      pathway. A recently recognized interaction between Ca(2+) and cAMP is the Ca(2+)
      induced cAMP formation in the mitochondrial matrix. Here we describe that soluble
      adenylyl cyclase (sAC) is expressed in H295R adrenocortical cells. Mitochondrial
      cAMP formation, monitored with a mitochondria-targeted fluorescent sensor
      (4mtH30), is enhanced by HCO3(-) and the Ca(2+) mobilizing agonist angiotensin
      II. The effect of angiotensin II is inhibited by 2-OHE, an inhibitor of sAC, and
      by RNA interference of sAC, but enhanced by an inhibitor of phosphodiesterase
      PDE2A. Heterologous expression of the Ca(2+) binding protein S100G within the
      mitochondrial matrix attenuates angiotensin II-induced mitochondrial cAMP
      formation. Inhibition and knockdown of sAC significantly reduce angiotensin II
      induced aldosterone production. These data provide the first evidence for a cell
      specific functional role of mitochondrial cAMP. 

PMID- 25958041
TI  - Fatty Acid-Binding Protein 4 mediates apoptosis via endoplasmic reticulum stress
      in mesangial cells of diabetic nephropathy.
AB  - Type 2 diabetes is characterized by hyperglycemia and deregulated lipid
      metabolism with increased plasma non-esterified fatty acids (NEFA). Apoptosis of
      glomerular cells is a hallmark in diabetic glomerulosclerosis. Fatty acid-binding
      protein 4 (FABP4), a carrier protein for fatty acids, has been linked to diabetes
      and diabetic nephropathy (DN). Here we aimed to investigate the link between
      FABP4 and apoptosis in diabetic glomerulosclerosis. We first evaluated the
      presence of FABP4 and ER stress markers as well as apoptosis-related proteins in
      renal biopsies of patients with DN. Then we used FABP4 inhibitor BMS309403 or
      siRNA to further investigate the role of FABP4 in ER stress and apoptosis induced
      by NEFA or high glucose in cultured human mesangial cells (HMCs). We found FABP4
      was expressed mainly in glomerular mesangial cells of the human renal biopsies
      and the glomerular FABP4 was increased in renal biopsies of DN. The up-regulation
      of FABP4 was accompanied with increased glucose-regulated protein 78 (GRP78) and
      Caspase-12 as well as down-regulated B-cell CLL/lymphoma 2 (Bcl-2) in glomeruli.
      Along with the induction of FABP4 and apoptosis, GRP78 and its three sensors as
      well as C/EBP homologous protein (CHOP) and Caspase-12 were induced in HMCs
      treated with NEFA or high glucose and these responses were attenuated or even
      abrogated by treating with FABP4 inhibitor or FABP4 siRNA. Ultrastructure
      observation confirmed the lipotoxicity of oleic acid by showing the morphological
      damage in HMCs. Our data suggest that FABP4 in glomerular mesangial cells is up
      regulated in DN and FABP4 mediates apoptosis via the ER stress in HMCs. 

PMID- 25958043
TI  - The androgen receptor has no direct antiresorptive actions in mouse osteoclasts.
AB  - Androgen deficiency or androgen receptor knockout (ARKO) causes high-turnover
      osteopenia, but the target cells for this effect remain unclear. To examine
      whether AR in osteoclasts directly suppresses bone resorption, we crossed AR
      floxed with cathepsin K-Cre mice. Osteoclast-specific ARKO (ocl-ARKO) mice showed
      no changes neither in osteoclast surface nor in bone microarchitecture nor in the
      response to orchidectomy and androgen replacement, indicating that the AR in
      osteoclasts is not critical for bone maintenance. In line with the lack of a bone
      phenotype, the levels of AR were very low in osteoclast-enriched cultures derived
      from bone marrow (BM) and undetectable in osteoclasts generated from spleen
      precursors. Since tibiae of ubiquitous ARKO mice displayed increased osteoclast
      counts, the role of AR was further explored using cell cultures from these
      animals. Osteoclast generation and activity in vitro were similar between ARKO
      and wildtype control (WT) mice. In co-culture experiments, BM stromal cells
      (BMSCs) were essential for the suppressive action of AR on osteoclastogenesis and
      osteoclast activity. Stimulation with 1,25(OH)2 vitamin D3 increased Rankl and
      decreased Tnfsf11 (osteoprotegerin, Opg) gene expression in BMSCs more than in
      osteoblasts. This increase in the Rankl/Opg ratio following 1,25(OH)2D3
      stimulation was lower, not higher, in ARKO mice. Runx2 expression in BMSCs was
      however higher in ARKO vs. WT, suggesting that ARKO mice may more readily commit
      osteoprogenitor cells to osteoblastogenesis. In conclusion, the AR does not seem
      to suppress bone resorption through direct actions in osteoclasts. BMSCs may
      however represent an alternative AR target in the BM milieu. 

PMID- 25958042
TI  - Lipopolysaccharide-induced murine embryonic resorption involves changes in
      endocannabinoid profiling and alters progesterone secretion and inflammatory
      response by a CB1-mediated fashion.
AB  - Genital tract infections are a common complication of human pregnancy that can
      result in miscarriage. We have previously shown that a lipopolysaccharide (LPS)
      induces embryonic resorption in a murine model of inflammatory miscarriage. This
      is accompanied by a dramatic decrease in systemic progesterone levels associated
      with a robust pro-inflammatory response that results in embryo resorption. Here,
      we tested the hypothesis that the endogenous cannabinoid system (eCS), through
      cannabinoid receptor 1 (CB1), plays a role in regulating progesterone levels and,
      therefore, the pro-inflammatory response. We show that LPS treatment in pregnant
      mice causes significant changes in the eCS ligands, which are reversed by
      progesterone treatment. We further show the CB1-KO mice maintain higher plasma
      progesterone levels after LPS treatment, which is associated with a feebler
      uterine inflammatory response and a significant drop in embryo resorption. These
      data suggest that manipulation of CB1 receptors and/or ligands is a potential
      therapeutic avenue to decrease infection-induced miscarriage. 

PMID- 25958044
TI  - Gonadotropin and kisspeptin gene expression, but not GnRH, are impaired in cFOS
      deficient mice.
AB  - cFOS is a pleiotropic transcription factor, which binds to the AP1 site in the
      promoter of target genes. In the pituitary gonadotropes, cFOS mediates induction
      of FSHbeta and GnRH receptor genes. Herein, we analyzed reproductive function in
      the cFOS-deficient mice to determine its role in vivo. In the pituitary cFOS is
      necessary for gonadotropin subunit expression, while TSHbeta is unaffected.
      Additionally, cFOS null animals have the same sex-steroid levels, although
      gametogenesis is impeded. In the brain, cFOS is not necessary for GnRH neuronal
      migration, axon targeting, cell number, or mRNA levels. Conversely, cFOS nulls,
      particularly females, have decreased Kiss1 neuron numbers and lower Kiss1 mRNA
      levels. Collectively, our novel findings suggest that cFOS plays a cell-specific
      role at multiple levels of the hypothalamic-pituitary-gonadal axis, affecting
      gonadotropes but not thyrotropes in the pituitary, and kisspeptin neurons but not
      GnRH neurons in the hypothalamus, thereby contributing to the overall control of
      reproduction. 

PMID- 25958046
TI  - Obesity associated Lyplal1 gene is regulated in diet induced obesity but not
      required for adipocyte differentiation.
AB  - Obesity and its associated morbidities represent one of the major and most
      rapidly expanding health epidemics in the world. Recent genome-wide association
      studies (GWAS) have identified several variants in LYPLAL1 gene that are
      significantly associated with central obesity preferentially in females. However,
      the exact function of this gene in adipose tissue development and obesity remains
      completely uncharacterized. We found murine Lyplal1 gene demonstrated a depot and
      sex-specific expression profile in white adipose tissues (WAT), and was
      significantly reduced in the epididymal and retroperitoneal fats in a murine
      model of high fat diet induced obesity (DIO). Lyplal1 mRNA was mildly up
      regulated during adipogenesis and enriched in mature adipocytes through a
      PPARgamma-independent mechanism. However, overexpression and knockdown of Lyplal1
      did not significantly perturb adipocyte differentiation, triacylglycerol
      accumulation and/or insulin signaling. These data highlight a depot-specific
      marked reduction of Lyplal1 transcripts in diet induced obesity but a dispensable
      role of Lyplal1 in adipose tissue development. 

PMID- 25958045
TI  - Immunohistochemical, genetic and clinical characterization of sporadic
      aldosterone-producing adenomas.
AB  - Adrenal glands removed for unilateral primary aldosteronism (PA) display marked
      histological heterogeneity. Recently reported somatic mutations in KCNJ5, ATP1A1,
      ATP2B3 and CACNA1D can partially account for these differences. In this study we
      aimed at combining phenotypic and genotypic characteristics, integrating genetic
      and immunohistochemistry correlates in sporadic PA. Seventy-one adrenal glands
      have been included in the study and analyzed for mutations in KCNJ5, ATP1A1,
      ATP2B3 and CACNA1D. Histological examination and immunohistochemical staining for
      CYP11B1 (11beta-hydroxylase) and CYP11B2 (aldosterone synthase) were performed on
      aldosterone-producing adenomas (APAs) and adjacent adrenal cortex. In our cohort,
      the final histopathological diagnosis was multinodular hyperplasia in 22.5% of
      the patients and single nodule in 77.5%. Forty-five percent of the removed
      adrenals displayed extra-APA CYP11B2-positive cell nests (B2-CN). Among adrenal
      vein sampling parameters the suppression of contralateral adrenal was more
      frequent and the lateralization index was higher in the subgroup of patients
      without extra-APA B2-CN compared to the subgroup with extra-APA B2-CN. KCNJ5
      mutated APAs were composed mainly of zona fasciculata-like cells with high
      expression of CYP11B1, while ATP1A1, ATP2B3 and CACNA1D-mutated APAs presented
      more frequently a zona-glomerulosa-like phenotype with high expression of
      CYP11B2. We observed a significant inverse correlation between CYP11B2 expression
      and the size of the nodules and, if CYP11B2 expression was corrected for tumor
      volume, a significant correlation with plasma aldosterone and aldosterone to
      renin ratio. Our findings indicate that combination of genotyping and
      immunohistochemistry improves the final histopathological diagnosis between
      single nodule and multinodular hyperplasia of the assessed adrenals. 

PMID- 25958047
TI  - Recent advances in hopanoids analysis: Quantification protocols overview, main
      research targets and selected problems of complex data exploration.
AB  - Pentacyclic triterpenoids, particularly hopanoids, are organism-specific
      compounds and are generally considered as useful biomarkers that allow
      fingerprinting and classification of biological, environmental and geological
      samples. Simultaneous quantification of various hopanoids together with battery
      of related non-polar and low-molecular mass compounds may provide principal
      information for geochemical and environmental research focusing on both modern
      and ancient investigations. Target compounds can be derived from microbial
      biomass, water columns, sediments, coals, crude fossils or rocks. This create
      number of analytical problems due to different composition of the analytical
      matrix and interfering compounds and therefore, proper optimization of
      quantification protocols for such biomarkers is still the challenge. In this work
      we summarizing typical analytical protocols that were recently applied for
      quantification of hopanoids like compounds from different samples. Main steps
      including components of interest extraction, pre-purification, fractionation,
      derivatization and quantification involving gas (1D and 2D) as well as liquid
      separation techniques (liquid-liquid extraction, solid-phase extraction, planar
      and low resolution column chromatography, high-performance liquid chromatography)
      are described and discussed from practical point of view, mainly based on the
      experimental papers that were published within last two years, where significant
      increase in hopanoids research was noticed. The second aim of this review is to
      describe the latest research trends concerning determination of hopanoids and
      related low-molecular mass lipids analyzed in various samples including
      sediments, rocks, coals, crude oils and plant fossils as well as stromatolites
      and microbial biomass cultivated under different conditions. It has been found
      that majority of the most recent papers are based on uni- or bivariate approach
      for complex data analysis. Data interpretation involves number of physicochemical
      parameters and hopanoids quantities or given biomarkers mass ratios derived from
      high-throughput separation and detection systems, typically GC-MS and HPLC-MS.
      Based on quantitative data reported in recently published experimental works it
      has been demonstrated that multivariate data analysis using e.g. principal
      components computations may significantly extend our knowledge concerning proper
      biomarkers selection and samples classification by means of hopanoids and related
      non-polar compounds. 

PMID- 25958048
TI  - Evidence of estrone-sulfate uptake modification in young and middle-aged rat
      prostate.
AB  - High plasma exposure to estrogens is often associated with prostate cancer.
      Reducing this phenomenon may present therapeutic benefits. The involvement of
      estrone sulphate (E1S), the most abundant circulating estrogen in men, has been
      partially studied in this age-related pathology. To investigate the consequences
      of plasma E1S overload on blood and prostate sex steroid levels and inflammatory
      tissue responses, young and middle-aged male rats were treated with E1S with or
      without steroid sulfatase (STS) inhibitor STX64 for 21 consecutive days. A plasma
      and prostate tissue steroid profile was determined. STS activity, mRNA expression
      of E1S organic anion transporting polypeptides (slco1a2, slco2b1, slco4a1) and
      pro-inflammatory cytokines (Il1-beta, Il6, TNF-alpha) were evaluated in prostate
      tissue according to age and treatment group. A significant correlation between
      plasma and prostate steroid levels related to hormone treatment was observed in
      all rat age groups. However, while the E1S level in prostate tissue increased in
      middle-aged treated rats (p<0.0001), no significant variation was observed in
      young treated rats. The protective effect of STX64 during E1S infusion was
      observed by the maintenance of low free estrogen concentrations in both plasma
      and tissue. However, this protection was not associated with mRNA expression
      stability of pro-inflammatory cytokines in older rat prostate. These results
      suggest that E1S uptake in rat prostate cells increases during aging. Therefore,
      if a similar phenomenon existed in men, preventively reducing the STS activity
      could be of interest to limit uptake of estrogens in prostate when high E1S
      plasma level is assayed. 

PMID- 25958049
TI  - Arthroscopic treatment of bony loose bodies in the subacromial space.
AB  - INTRODUCTION: Multiple bony loose bodies in the subacromial space caused form
      cartilage or bone cells and continue to grow. PRESENTATION OF CASE: A 58-year-old
      man with two-year history of swelling and pain of the right shoulder. He had no
      history of tuberculosis and rheumatoid arthritis. Magnetic resonance (MR) images
      showed some bony loose bodies in the subacromial space. The removal of loose
      bodies and bursa debridement were performed arthroscopically. Histological
      diagnosis of them was synovitis with fibrous bodies. DISCUSSION: Extra-articular
      loose bodies is extremely rare, especially in the subacromial space, which maybe
      originated in the proliferative synovial bursa. Most authors recommend open
      removal to relive the pain, but there were choice to apply arthroscopy to remove
      them. CONCLUSION: The mechanism of formation of bony loose bodies is not clear,
      may be associated with synovial cartilage metaplasia. Arthroscopic removal of
      loose bodies and bursa debridement is a good option for treatment of the loose
      body in the subacromial space, which can receive good function.

PMID- 25958050
TI  - Single incision cholecystectomy using a clipless technique with LigaSure in a
      resource limited environment: The Bahamas experience.
AB  - BACKGROUND: Scarless/single-incision laparoscopic cholecystectomy (SILC) is a new
      procedure. It affords a superior cosmetic outcome when compared to conventional
      laparoscopic cholecystectomy. We examine the application of this technique using
      LigaSure via a clipless method. The present study looks at the experience of a
      single surgeon using this method with initial evaluation of the safety,
      feasibility, affordability, and benefits of this procedure. METHODS: Twenty-eight
      patients underwent transumbilical SILC at Doctors Hospital from January to
      December, 2014. The cohort included both emergency and elective patients. There
      was no difference in the preoperative work-up as indicated. To perform the
      operation, a 2-2.5-cm linear incision was made through the umbilicus and the
      single port platform utilized. A 10mm 30-degree laparoscope, a 5mm LigaSure and
      straight instruments were used to perform the laparoscopic cholecystectomy
      procedure. RESULTS: All patients except two were operated on successfully.
      Conversion was considered the placement of an additional epigastric/Right upper
      quadrant (RUQ) port. The conversion rate to standard LC was 7%. No patient was
      converted to open cholecystectomy. In the 28 successfully completed patients, the
      median duration of the operation was 38.5min and estimated operative blood loss
      was 24ml. Patients were commenced on liquid diet immediately on being fully
      conscious and after return to the ward with an estimated time of 6h. The mean
      postoperative hospital stay was 1.4 days. Follow-up visits were conducted for all
      patients at 2-weeks intervals and continued for 6 weeks after surgery where
      possible. Two patients developed wound infections. All patients were satisfied
      with the good cosmetic effect of the surgery. The total satisfaction rate was
      100%. CONCLUSIONS: SILC is a safe and feasible technique for operating with
      scarless outcomes and reducing perioperative discomfort at the same time. The
      GelPOINTTM is a safe and feasible platform to be used. The procedure can be
      accomplished using regular instruments and laparoscope. Curved instruments and a
      bariatric length laparoscope may make the procedure easier and result in greater
      time saving. The addition of LigaSureTM decreases the complexity of the
      operation, decreases operative time and blood loss. The technique is economical
      in a resource-limited environment.

PMID- 25958051
TI  - Genetic polymorphism analysis of the drug-metabolizing enzyme CYP2C9 in a Chinese
      Tibetan population.
AB  - OBJECTIVES: The enzymatic activity of CYP2C9 results in broad inter-individual
      variability in response to certain pharmacotherapies. The present study aimed to
      screen Tibetan volunteers for CYP2C9 genetic polymorphisms. Previous research has
      focused on Han Chinese patients, while little is known about the genetic
      variation of CYP2C9 in Tibetan populations. METHODS: We used DNA sequencing to
      investigate the promoter, exons and surrounding introns, and 3'-untranslated
      region of the CYP2C9 gene in 96 unrelated healthy Tibetan individuals. RESULTS:
      We identified 26 different CYP2C9 polymorphisms in the Tibetan population,
      including two novel variants detected in exon 9 (50193G>A and 50197G>C). In
      addition, we determined the allele frequencies of CYP2C9*1 and *3 were 93.75% and
      5.73%, respectively. The rare CYP2C9*55 allele was also found in 0.52% of the
      study population. CONCLUSIONS: Our results provide information on CYP2C9
      polymorphisms in Tibetan individuals, which may help to optimize pharmacotherapy
      effectiveness by providing personalized medicine to this ethnic group.

PMID- 25958052
TI  - The application of S.T.O.N.E. nephrolithometry in pediatric patients with upper
      urinary tract calculi treated with mini-percutaneous nephrolithotomy.
AB  - The purpose of this study is to verify the applicability of S.T.O.N.E.
      nephrolithometry in pediatric patients. 103 cases of pediatric patients younger
      than 4 years old with upper urinary tract calculi treated with mini-percutaneous
      nephrolithotomy from January 2012 to March 2014 were retrospectively reviewed and
      evaluated using this scoring system. All procedures were performed under general
      anesthesia, using a 14-French nephroscope through a 16-French working access. All
      patients were divided into two groups according to the stages of the operations,
      Group A for one-stage operation and Group B for two-stage operation. 87 cases
      were male and 16 cases were female with the mean age of 26.5 months. The total
      operation time of group A was 45.89+/-5.43 min, and 54.62+/-5.58 min of group B
      (p=0.000). The hospitalization for group A and group B was 6.63+/-1.34 and 7.23+/
      1.24 days, respectively (p=0.134). The total S.T.O.N.E. score was 5.93+/-0.67 for
      Group A, and 7.92+/-1.04 for Group B (p=0.000). On further dividing each group
      into low/moderate/high complexity according to the total score, more cases of
      low/moderate complexity in group A and more cases of moderate/high complexity in
      group B (chi2=38.096, p=0.000) were reported. Our data suggest that S.T.O.N.E.
      nephrolithometry is applicable in pediatric upper urinary tract calculi
      assessment and predictive for the complexity of the operation, hospitalization,
      and even complications after the operation. Yet modification may be necessary to
      make this scoring system more distinguishable for pediatric cases.

PMID- 25958054
TI  - The concept of capacity in Australian mental health law reform: Going in the
      wrong direction?
AB  - The six Australian states and two territories each have legislation that enables
      the involuntary detention and treatment of individuals diagnosed with mental
      illness who are considered in need of treatment and where there is evidence of a
      risk of harm to self or others. A number of governments have undertaken or are
      currently undertaking reviews of mental health laws in light of the Australian
      Government's ratification of the Convention on the Rights of Persons with
      Disabilities. While United Nations bodies have made it clear that laws which
      enable the detention of and substituted decision-making for persons with
      disabilities should be abolished, debates in Australia about the reform of mental
      health legislation have largely focused on Article 12 of the CRPD and what is
      meant by the right of persons with disabilities to enjoy legal capacity on an
      equal basis with others. It is argued that a more holistic view of the CRPD
      rather than the current narrow focus on Article 12 would best serve the needs of
      persons with mental impairments. 

PMID- 25958053
TI  - Biochemical diagnosis in 3040 kidney stone formers in Argentina.
AB  - Nephrolithiasis is a frequent condition in urology that has an important
      recurrence and high impact in health economy. Knowing the biochemical
      abnormalities implicated in its pathogenesis is mandatory to establish
      therapeutic aims. Our objectives are to present the results in 3040 kidney stone
      formers in Argentina. All patients were selected after completing an ambulatory
      metabolic protocol with diagnostic purposes. There were 1717 men, (56.48%), with
      a mean age of 45+/-12 years, and 1323 women, (43.52%), mean age 44+/-12 years.
      2781 patients had biochemical abnormalities, (91.49%), and were arbitrarily
      divided in two groups: those who had only one (single) biochemical abnormality
      (n=2156) and those who had associated abnormalities (n=625). No biochemical
      abnormalities were found in 259 patients (8.51%). The abnormalities present,
      single and associated, in order of frequency, were idiopathic hypercalciuria,
      (56.88%), hyperuricosuria (21.08%), unduly acidic urine (10.95%), hypocitraturia
      (10.55%), hypomagnesuria (7.9%), primary hyperparathyroidism (3.01%),
      hyperoxaluria (2.6%), and cystinuria (0.32%). We performed in 484 patient's stone
      composition and found calcium oxalate stones related to idiopathic hypercalciuria
      predominantly while uric acid stones to unduly acidic urine. In conclusion, the
      biochemical abnormalities described are similar to those found in a previous
      series of our own and to those reported in the literature. Its diagnosis is
      important to therapeutic purposes to avoid eventual recurrence.

PMID- 25958055
TI  - Experiencing Loss: A Muslim Widow's Bereavement Narrative.
AB  - In this article, we explore how Islam, minority status and refugee experiences
      intersect in shaping meaning-making processes following bereavement. We do this
      through a phenomenological analysis of a biographical account of personal loss
      told by Aisha, a Muslim Palestinian refugee living in Denmark, who narrates her
      experience of losing her husband to lung cancer. By drawing on a religious
      framework, Aisha creates meaning from her loss, which enables her to incorporate
      this loss into her life history and sustain agency. Her narrative invites wider
      audiences to witness her tale of overcoming loss, thus highlighting the complex
      way in which religious beliefs, minority status and migration history come
      together in shaping meaning-making processes, and the importance of reciprocity
      in narrative studies. 

PMID- 25958056
TI  - Sensitivity to systemic therapy for metastatic breast cancer in CHEK2 1100delC
      mutation carriers.
AB  - PURPOSE: The role of CHEK2 in DNA repair by homologous recombination suggests
      that CHEK2-associated breast cancer (BC) patients might be more sensitive to
      chemotherapy inducing double-strand DNA breaks, but results hereon are lacking.
      We compared the sensitivity to first-line chemotherapy and endocrine therapy
      between CHEK2 1100delC and non-CHEK2 metastatic breast cancer (MBC) patients.
      METHODS: Sixty-two CHEK2 1100delC MBC patients were selected from three cohorts
      genotyped for CHEK2 1100delC (one non-BRCA1/2 cohort and two sporadic cohorts).
      Controls were 62 non-CHEK2 MBC patients, matched for age at and year of primary
      BC diagnosis, and year of metastatic disease. Objective response rate (complete
      and partial response) to, and progression-free survival (PFS) and overall
      survival (OS) after start of first-line chemotherapy and endocrine therapy were
      compared between CHEK2 and non-CHEK2 patients. RESULTS: Median age at BC
      diagnosis was 46 and 51 years at MBC diagnosis. First-line chemotherapy consisted
      of anthracycline-based chemotherapy (n = 73), taxanes (n = 16), CMF(-like)
      chemotherapy (n = 33) and taxane/anthracycline regimens (n = 2). CHEK2 and non
      CHEK2 patients had a comparable objective response rate (44 vs. 52 %). Also, PFS
      and OS after start of chemotherapy were comparable between both patient groups
      (hazard ratio 0.91; 95 % confidence interval 0.63-1.30 and 1.03; 95 % CI 0.71
      1.49, respectively). Thirty-six CHEK2 and 32 non-CHEK2 patients received first
      line endocrine therapy (mainly tamoxifen) for MBC. No significant differences
      were observed in objective response rate to, and PFS and OS after start of
      endocrine therapy. CONCLUSION: No differential efficacy of chemotherapy and
      endocrine therapy given for MBC was observed in CHEK2 versus non-CHEK2 patients.

PMID- 25958057
TI  - The False-Profile View May Be Used to Identify Cam Morphology.
AB  - PURPOSE: To identify the accuracy of measuring the alpha angle on the false
      profile, anteroposterior (AP), and 90 degrees  Dunn lateral views of the hip as
      compared with computed tomography (CT) scan findings. METHODS: Forty patients
      were needed to have power greater than 80%. Forty-five consecutive patients
      undergoing hip arthroscopy were retrospectively reviewed with preoperative radial
      oblique CT reformatted scans and plain radiographs. Alpha angles were measured on
      plain radiographs (AP, 90 degrees  Dunn lateral, and false profile) and CT
      reformatted views. Abnormal alpha angles were considered greater than 50.5
      degrees . Two orthopaedic surgeons independently measured the images, and the
      results were compared between imaging modalities. RESULTS: The false-profile view
      was 60% sensitive and 89.0% specific for diagnosing cam deformities of the hip.
      All radiographs combined were 86% sensitive and 75% specific for diagnosing cam
      deformities. The false-profile view most strongly correlated with the 2-o'clock
      (R = 0.746, P = .001) and 3-o'clock (R = 0.698, P < .0001) positions. An
      intraclass correlation coefficient of 0.81 was found for measurement of the alpha
      angle on the false-profile view. CONCLUSIONS: This study has proved that the
      false-profile view effectively characterizes cam deformity, especially anterior
      deformity at the 3-o'clock position. Measuring the alpha angle on the false
      profile view appears to be reproducible. The false-profile view along with
      standing AP pelvis and 90 degrees  Dunn lateral views of the hip comprises a good
      screening radiographic series for patients presenting with symptoms of
      femoroacetabular impingement. LEVEL OF EVIDENCE: Level III, diagnostic study.

PMID- 25958058
TI  - Clinical Outcome of Posterior Cruciate Ligament Reconstruction With and Without
      Remnant Preservation.
AB  - PURPOSE: The purpose of this study was to analyze clinical outcomes in patients
      who underwent posterior cruciate ligament reconstruction (PCLR) with and without
      remnant preservation. METHODS: A search of the literature was performed with the
      established medical databases Medline, Embase, and the Cochrane Register. Two
      authors screened the selected articles for title, abstract, and full text in
      accordance with predefined inclusion and exclusion criteria. The inclusion
      criteria were as follows: English-language articles on isolated posterior
      cruciate ligament injury; clinical trials with a clear description of surgical
      technique; outcome evaluation using a well-defined knee score, arthrometry, and
      posterior stress radiography; follow-up longer than 2 years; and a Coleman
      Methodology Score (CMS) of 65 points or greater. The methodologic quality of all
      articles was assessed by 2 authors according to the CMS. RESULTS: Eleven studies
      were included, with a mean CMS of 78.9 points (SD, 5.37 points). There was no
      direct comparative study between remnant-preserving PCLR and standard PCLR. At
      final follow-up, the knees of 72% to 100% of patients who underwent remnant
      preserving PCLR and 41% to 95% of patients who underwent standard PCLR were rated
      as normal or nearly normal on the International Knee Documentation Committee
      subjective knee assessment. Patients who underwent remnant-preserving PCLR showed
      an increase of 16.4 to 47 points in Lysholm scores, and patients who underwent
      standard PCLR showed an increase of 22 to 29 points. The ranges of mean
      postoperative side-to-side differences on KT-1000 (MEDmetric, San Diego, CA)
      testing were 0.7 to 2.8 mm in patients who underwent remnant-preserving PCLR and
      1 to 3.5 mm in patients who underwent standard PCLR. The ranges of mean
      postoperative side-to-side differences on stress radiography were 2.2 to 5 mm in
      patients who underwent remnant-preserving PCLR and 4.7 to 6 mm in patients who
      underwent standard PCLR. CONCLUSIONS: All studies on PCLR with remnant
      preservation showed satisfactory outcomes despite using numerous surgical
      techniques, graft types, intervals from injury to surgery, and follow-up periods.
      LEVEL OF EVIDENCE: Level IV, systematic review of Level II through IV studies.

PMID- 25958060
TI  - A gesture-controlled projection display for CT-guided interventions.
AB  - PURPOSE: The interaction with interventional imaging systems within a sterile
      environment is a challenging task for physicians. Direct physician-machine
      interaction during an intervention is rather limited because of sterility and
      workspace restrictions. METHODS: We present a gesture-controlled projection
      display that enables a direct and natural physician-machine interaction during
      computed tomography (CT)-based interventions. Therefore, a graphical user
      interface is projected on a radiation shield located in front of the physician.
      Hand gestures in front of this display are captured and classified using a leap
      motion controller. We propose a gesture set to control basic functions of
      intervention software such as gestures for 2D image exploration, 3D object
      manipulation and selection. Our methods were evaluated in a clinically oriented
      user study with 12 participants. RESULTS: The results of the performed user study
      confirm that the display and the underlying interaction concept are accepted by
      clinical users. The recognition of the gestures is robust, although there is
      potential for improvements. The gesture training times are less than 10 min, but
      vary heavily between the participants of the study. The developed gestures are
      connected logically to the intervention software and intuitive to use.
      CONCLUSIONS: The proposed gesture-controlled projection display counters current
      thinking, namely it gives the radiologist complete control of the intervention
      software. It opens new possibilities for direct physician-machine interaction
      during CT-based interventions and is well suited to become an integral part of
      future interventional suites.

PMID- 25958059
TI  - Bowel Damage as Assessed by the Lemann Index is Reversible on Anti-TNF Therapy
      for Crohn's Disease.
AB  - BACKGROUND AND AIMS: Bowel damage [BD] will develop in the majority of Crohn's
      disease [CD] patients. Recently, the Lemann Index [LI] was developed to measure
      BD. METHODS: This was a prospective single-center cohort study. All included
      patients underwent full evaluation for bowel damage before starting anti-TNF
      therapy and every year thereafter. BD at baseline and during follow-up was
      measured using the LI. We assessed the impact of anti-TNF therapy on BD. We also
      assessed the sensitivity to change of the LI and the relationship between BD
      progression and disease outcomes, including the need for surgery. RESULTS: Thirty
      CD patients were enrolled [13 on infliximab, 17 on adalimumab]. Median baseline
      LI was 9.1 [range, 1.6-34.1]. Median follow up was 32.5 months [range, 10-64].By
      a ROC curve analysis, a LI >4.8 defined CD subjects with BD. Any change >0.3 in
      the LI was related to BD change [AUC 0.98]. During follow-up, 83% of subjects had
      BD regression and 17% had BD progression. Anti-TNF therapy significantly reduced
      LI at 12 months [p=0.007]. Subjects with BD progression were more likely to
      undergo major abdominal surgery through the follow-up period [HR 0.19, p=0.005].
      CONCLUSION: The LI has good sensitivity to change. Anti-TNFs agents are able to
      reverse BD in some CD patients. BD progression as measured by the LI may be
      predictive of major abdominal surgery in these patients.

PMID- 25958061
TI  - Estimation of intraoperative brain shift by combination of stereovision and
      doppler ultrasound: phantom and animal model study.
AB  - PURPOSE: Combination of various intraoperative imaging modalities potentially can
      reduce error of brain shift estimation during neurosurgical operations. In the
      present work, a new combination of surface imaging and Doppler US images is
      proposed to calculate the displacements of cortical surface and deformation of
      internal vessels in order to estimate the targeted brain shift using a Finite
      Element Model (FEM). Registration error in each step and the overall performance
      of the method are evaluated. METHODS: The preoperative steps include constructing
      a FEM from MR images and extracting vascular tree from MR Angiography (MRA). As
      the first intraoperative step, after the craniotomy and with the dura opened, a
      designed checkerboard pattern is projected on the cortex surface and projected
      landmarks are scanned and captured by a stereo camera (Int J Imaging Syst Technol
      23(4):294-303, 2013. doi: 10.1002/ima.22064 ). This 3D point cloud should be
      registered to boundary nodes of FEM in the region of interest. For this purpose,
      we developed a new non-rigid registration method, called finite element drift
      that is more compatible with the underlying nature of deformed object. The
      presented algorithm outperforms other methods such as coherent point drift when
      the deformation is local or non-coherent. After registration, the acquired
      displacement vectors are used as boundary conditions for FE model. As the second
      step, by tracking a 2D Doppler ultrasound probe swept on the parenchyma, a 3D
      image of deformed vascular tree is constructed. Elastic registration of this
      vascular point cloud to the corresponding preoperative data results the second
      series of displacement vector applicable to closest internal nodes of FEM. After
      running FE analysis, the displacement of all nodes is calculated. The brain shift
      is then estimated as displacement of nodes in boundary of a deep target, e.g., a
      tumor. We used intraoperative MR (iMR) images as the references for measuring the
      performance of the brain shift estimator. In the present study, two set of tests
      were performed using: (a) a deformable brain phantom with surface data and (b) an
      alive brain of an approximately big dog with surface data and US Doppler images.
      In our designed phantom, small tubes connected to an inflatable balloon were
      considered as displaceable targets and in the animal model, the target was
      modeled by a cyst which was created by an injection. RESULTS: In the phantom
      study, the registration error for the surface points before FE analysis and for
      the target points after running FE model were <0.76 and 1.4 mm, respectively. In
      a real condition of operating room for animal model, the registration error was
      about 1 mm for the surface, 1.9 mm for the vascular tree and 1.55 mm for the
      target points. CONCLUSIONS: The proposed projected surface imaging in conjunction
      with the Doppler US data combined in a powerful biomechanical model can result an
      acceptable performance in calculation of deformation during surgical navigation.
      However, the projected landmark method is sensitive to ambient light and surface
      conditions and the Doppler ultrasound suffers from noise and 3D image
      construction problems, the combination of these two methods applied on a FEM has
      an eligible performance.

PMID- 25958062
TI  - Creation and validation of a condition-specific venous thromboembolism risk
      assessment tool for ventral hernia repair.
AB  - BACKGROUND: We used the database of the American College of Surgeons National
      Surgical Quality Improvement Program to (1) identify risk factors for 30-day
      venous thromboembolism (VTE) after ventral hernia repair (VHR) and (2) to create
      and validate a condition-specific assessment tool for the risk of VTE. METHODS:
      Open and laparoscopic VHR patients in the American College of Surgeons National
      Surgical Quality Improvement Program were identified using Current Procedural
      Terminology code. The occurrence of VTE, including deep-venous thrombosis (DVT)
      or pulmonary embolus, within 30 days postoperatively was the primary outcome.
      Regression-based analysis and subsequent bootstrap analysis created a weighted
      VTE risk assessment model (RAM) for ventral hernia repair. The weighted RAM was
      used to risk-stratify patients for both 30-day VTE risk and 30-day risk for
      medical and surgical complications. RESULTS: Data for 113,873 hernia repair
      patients were obtained; 30-day deep-venous thrombosis, pulmonary embolus, and VTE
      rates were 0.59%, 0.43%, and 0.92%, respectively. The average time to VTE was
      10.8 days. A 14-factor, weighted RAM was created. The weighted risk score
      identified a 25-fold variability (from 0.20 to 4.97%) in VTE risk among the
      overall VHR population. Although created to risk-stratify for VTE, the risk score
      also risk-stratified for 30-day medical and surgical complications, inpatient
      duration of stay, and 30-day mortality. CONCLUSION: The 30-day VTE risk after VHR
      is 0.92%, but a 25-fold variability in VTE risk exists among the overall hernia
      population. We demonstrate that a weighted VTE RAM quantifies VTE risk among the
      population undergoing ventral hernia repair, and that VTE risk score can also be
      used to risk-stratify for 30-day medical and surgical complications as well as
      mortality.

PMID- 25958063
TI  - Alternative end points for trauma studies: A survey of academic trauma surgeons.
AB  - INTRODUCTION: Changing the epidemiology of trauma makes traditional end points
      like 30-day mortality less than ideal. Many alternative end points have been
      suggested; however, they are not yet accepted by the trauma community or
      regulatory bodies. This study characterizes opinions about the adequacy of
      accepted end points of studies of trauma and the appropriateness of several novel
      end points. METHODS: An electronic survey was administered to all members of the
      American Association for the Surgery of Trauma. Questions involved demographics,
      research experience, appropriateness of proposed study end points, and the role
      of nontraditional, surrogate, and composite end points. RESULTS: Response rate
      was 16% (141 of 873) with 74% of respondents practicing at Level 1 Trauma
      Centers. The respondents were very experienced, with 81% reporting >10 years of
      practice at the attending level and 87% actively involved in research. The
      majority of respondents rated the following end points favorably: 24-hour
      survival, 30-day survival, and time to control of acute hemorrhage with approval
      rates of 82%, 78%, and 76%, respectively. Six-hour survival, intensive care unit
      free survival, and days free of multiorgan failure were rated as appropriate or
      very appropriate less than 66% of the time. Only 45% of respondents judged the
      currently used end points of trauma to be appropriate. More than 80% respondents
      disagreed or strongly disagreed that there was no role for of surrogate or
      composite endpoints in research of trauma resuscitation. CONCLUSION: There is
      strong interest in finding efficient end points in trauma research that are both
      specific and reflect the changing epidemiology of trauma death. The alternative
      end points of 24-hour survival and time to control of acute hemorrhage had
      similar approval rates to 30-day mortality.

PMID- 25958064
TI  - Prognostic significance of peritoneal lavage cytology at three cavities in
      patients with gastric cancer.
AB  - BACKGROUND: We sought to determine the prognostic significance of intraoperative
      peritoneal lavage cytology (CY) at 3 different abdominal cavities and establish
      the optimal treatment for gastric cancer patients with positive peritoneal
      cytology (CY1). METHODS: A total of 1,039 patients with primary gastric
      adenocarcinoma who underwent CY at 3 cavities (Douglas' pouch, left subphrenic
      cavity, and right subhepatic cavity) were enrolled; 116 (11%) patients had at
      least one positive cavity. We retrospectively analyzed the clinicopathologic
      characteristics and survival of these 116 patients with CY1. RESULTS: Seventeen
      (15%) of the patients had negative cytology at Douglas' pouch but positive
      cytology at one or both of the other cavities. The 116 patients' overall 2-year
      survival rate was 22.9%, with the median survival time of 11 months. The overall
      2-year survival rates for the patients with positive cytology at 1, 2, and 3
      cavities were 41.9%, 35.8%, and 15%, with median survival times of 17, 18, and 9
      months, respectively (P < .01). A multivariate analysis revealed that macroscopic
      type 4 tumor, R2 resection, lymph node metastasis, and postoperative chemotherapy
      were independent prognostic factors. Among the CY1 patients with type 4 tumors,
      there was no substantial difference in survival between the patients who
      underwent R1 or R2 resection, although the statistical power of this subgroup
      analysis was low. CONCLUSION: CY at 3 cavities might be a useful method to
      decrease the false-negative rate. Palliative gastrectomy for CY1 patients with
      type 4 tumors is still controversial.

PMID- 25958065
TI  - Thyroid incidentalomas detected on 18F-fluorodeoxyglucose-positron emission
      tomography/computed tomography: Thyroid Imaging Reporting and Data System
      (TIRADS) in the diagnosis and management of patients.
AB  - BACKGROUND: Our aim was to evaluate the role of the Thyroid Imaging Reporting and
      Data System (TIRADS) in the risk stratification of thyroid incidentalomas
      detected on (18)F-fluorodeoxyglucose-positron emission tomography/computed
      tomography ((18)F-FDG-PET/CT) scans. METHODS: Eighty-seven thyroid nodules in 84
      patients showing incidentally detected increased uptake on (18)F-FDG-PET/CT who
      also had ultrasonography (US)-guided fine needle aspiration performed were
      included. On review of the US images, a TIRADS category was assigned to each
      thyroid nodule based on the number of suspicious US features. The correlation
      between the TIRADS category and the standard uptake values (SUV) on (18)F-FDG
      PET/CT were calculated and compared. RESULTS: Of the 87 thyroid nodules, 47 (54%)
      were benign, and 40 (46%) were malignant. The malignancy rate of the TIRADS
      categories were as follows: 9% for category 3, 15% for category 4a, 39% for
      category 4b, 72% for category 4c, and 100.0% for category 5. Combining the TIRADS
      with the SUV showed increased specificity and positive predictive value but
      decreased sensitivity and negative predictive value compared with TIRADS alone
      (all P < .05). The area under the receiver operating characteristics curve value
      of TIRADS was the greatest, comparable with the combined TIRADS and SUV (0.737 to
      0.724, P = .788). CONCLUSION: TIRADS may be applied in the risk stratification of
      thyroid incidentalomas detected on (18)F-FDG-PET/CT. Considering the high
      malignancy rate of thyroid incidentalomas showing increased (18)F-FDG uptake,
      ultrasonography-guided fine needle aspiration is mandatory even if there are no
      suspicious features present on US.

PMID- 25958066
TI  - Resection versus ablation in hepatitis B virus-related hepatocellular carcinoma
      patients with portal hypertension: A propensity score matching study.
AB  - BACKGROUND: With recent improvements in operative techniques, many studies have
      reported that resection is safe for hepatocellular carcinoma (HCC) patients with
      portal hypertension (PHT). However, no direct evidence exists to compare
      resection with ablation in patients with hepatitis B virus (HBV)-related PHT.
      METHODS: Of 259 HBV-related PHT patients who met the Milan criteria, 123 patients
      underwent resection and 136 underwent ablation as a primary treatment.
      Complications were graded with the Clavien-Dindo system, and oncologic outcomes
      were analyzed with a propensity score matching (PSM) method. RESULTS: Compared
      with the ablation group, the resection group showed larger tumors, greater white
      blood cell counts, greater platelet counts, lower gamma-glutamyltransferase
      levels, and lower model of end stage liver disease scores (all P < .05). Although
      more frequent complications occurred in the resection group (P < .001), the
      difference was significant for the Grade I complications but not for Grade II-V
      complications. The recurrence-free survival (RFS) and overall survival (OS) rates
      were greater in the resection group than in the ablation group (P = .001 and P =
      .010, respectively). After one-to-one PSM, 77 resection patients and 77 ablation
      patients were selected for further analyses. The advantages of resection over
      ablation were still observed in RFS (P = .002) and OS (P = .012). Grade I-V
      complications were comparable between the 2 groups (all P > .100). CONCLUSION:
      Resection is safe and confers a survival advantage over ablation in HBV-related
      PHT patients. Resection may be recommended as an optimal treatment for these
      patients.

PMID- 25958067
TI  - Toward a standard approach to measurement and reporting of perioperative
      mortality rate as a global indicator for surgery.
AB  - INTRODUCTION: The proportion of patients who die during or after surgery,
      otherwise known as the perioperative mortality rate (POMR), is a credible
      indicator of the safety and quality of operative care. Its accuracy and
      usefulness as a metric, however, particularly one that enables valid comparisons
      over time or between jurisdictions, has been limited by lack of a standardized
      approach to measurement and calculation, poor understanding of when in relation
      to surgery it is best measured, and whether risk-adjustment is needed. Our aim
      was to evaluate the value of POMR as a global surgery metric by addressing these
      issues using 4, large, mixed, surgical datasets that represent high-, middle-,
      and low-income countries. METHODS: We obtained data from the New Zealand National
      Minimum Dataset, the Geelong Hospital patient management system in Australia, and
      purpose-built surgical databases in Pietermaritzburg, South Africa, and Port
      Moresby, Papua New Guinea. For each site, we calculated the POMR overall as well
      as for nonemergency and emergency admissions. We assessed the effect of admission
      episodes and procedures as the denominator and the difference between in-hospital
      POMR and POMR, including postdischarge deaths up to 30 days. To determine the
      need for risk-adjustment for age and admission urgency, we used univariate and
      multivariate logistic regression to assess the effect on relative POMR for each
      site. RESULTS: A total of 1,362,635 patient admissions involving 1,514,242
      procedures were included. More than 60% of admissions in Pietermaritzburg and
      Port Moresby were emergencies, compared with less than 30% in New Zealand and
      Geelong. Also, Pietermaritzburg and Port Moresby had much younger patient
      populations (P < .001). A total of 8,655 deaths were recorded within 30 days, and
      8-20% of in-hospital deaths occurred on the same day as the first operation. In
      hospital POMR ranged approximately 9-fold, from 0.38 per 100 admissions in New
      Zealand to 3.44 per 100 admissions in Pietermaritzburg. In New Zealand, in
      hospital 30-day POMR underestimated total 30-day POMR by approximately one third.
      The difference in POMR if procedures were used instead of admission episodes
      ranged from 7 to 70%, although this difference was less when central line and
      pacemaker insertions were excluded. Age older than 65 years and emergency
      admission had large, independent effects on POMR but relatively little effect in
      multivariate analysis on the relative odds of in-hospital death at each site.
      CONCLUSION: It is possible to collect POMR in countries at all level of
      development. Although age and admission urgency are strong, independent
      associations with POMR, a substantial amount of its variance is site-specific and
      may reflect the safety of operative and anesthetic facilities and processes. Risk
      adjustment is desirable but not essential for monitoring system performance. POMR
      varies depending on the choice of denominator, and in-hospital deaths appear to
      underestimate 30-day mortality by up to one third. Standardized approaches to
      reporting and analysis will strengthen the validity of POMR as the principal
      indicator of the safety of surgery and anesthesia care.

PMID- 25958069
TI  - Does race affect management and survival in hepatocellular carcinoma in the
      United States?
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related
      death, and its incidence is increasing in the United States. This analysis
      describes the association between race, treatment decisions, operative outcomes,
      and survival for patients with HCC. METHODS: The National Cancer Database was
      queried for all patients diagnosed with HCC from 1998 to 2011 (n = 143,692) who
      were white (76.9%), black (14.7%), or Asian (8.4%). Multivariate logistic
      regression was performed to determine factors that affected the likelihood of
      having surgery and postoperative mortality, and a Cox regression was performed to
      evaluate the effect of these factors on survival. RESULTS: The proportion of
      black patients with HCC increased in the United States during the 13-year period.
      There were no substantial differences among races in tumor size, grade, or
      overall clinical stage at the time of presentation; however, black patients were
      less likely to have surgery (odds ratio 0.69, 95% confidence interval 0.67-0.72).
      Of patients who had surgery, there were no significant differences in pathologic
      stage, margin negative resection rate, or 30-day mortality; however, black
      patients had the longest interval between diagnosis and surgery, as well as the
      worst overall adjusted survival (hazard ratio 1.14, 95% confidence interval 1.05
      1.25). These findings were independent of HCC stage, insurance provider, and
      socioeconomic status. CONCLUSION: Despite similar clinical presentation of HCC,
      substantial racial differences exist with regard to management and outcomes.
      Black patients are less likely to receive surgery for HCC and have worse long
      term survival, despite similar perioperative quality metrics. This difference in
      long-term survival may highlight neighborhood, cultural, or biological
      differences between races.

PMID- 25958068
TI  - Intraoperative guidance in parathyroid surgery using near-infrared fluorescence
      imaging and low-dose Methylene Blue.
AB  - BACKGROUND: Identification of diseased and normal parathyroid glands during
      parathyroid surgery can be challenging. The aim of this study was to assess
      whether near-infrared (NIR) fluorescence imaging using administration of a low
      dose Methylene Blue (MB) at the start of the operation could provide optical
      guidance during parathyroid surgery and assist in the detection of parathyroid
      adenomas. METHODS: Patients diagnosed with primary hyperparathyroidism planned
      for parathyroidectomy were included. Patients received 0.5 mg/kg MB intravenously
      directly after start of anesthesia. During the operation, NIR fluorescence
      imaging was performed to identify parathyroid adenomas. Imaging results were
      compared with a previous published feasibility study in which 12 patients
      received MB after intraoperative identification of the adenoma. RESULTS: A total
      of 13 patients were included in the current study. In 10 of 12 patients with a
      histologically proven adenoma, the adenoma was fluorescent. Mean signal to
      background ratio was 3.1 +/- 2.8. Mean diameter of the resected lesions was 17 +/
      9 mm (range 5-28 mm). Adenomas could be identified up to 145 minutes after
      administration, which was the longest timespan until resection. Interestingly, in
      3 patients, a total of 6 normal parathyroid glands (median diameter 2.5 mm) with
      a signal to background ratio of 1.8 +/- 0.4 were identified using NIR
      fluorescence imaging. CONCLUSION: Early administration of low-dose MB provided
      guidance during parathyroidectomy by identifying both parathyroid adenomas and
      normal parathyroid glands. In patients in whom difficult identification of the
      parathyroid adenoma is expected or when normal glands have to be identified, the
      administration of MB may improve surgical outcome.

PMID- 25958070
TI  - District-level surgery in Uganda: Indications, interventions and perioperative
      mortality.
AB  - BACKGROUND: The world's poorest 2 billion people, benefit from no more than about
      3.5% of the world's operative procedures. The burden of surgical disease is
      greatest in Africa, where operations could save many lives. Previous facility
      based studies have described operative procedure caseloads, but prospective
      studies investigating interventions, indications and perioperative mortality
      rates (POMR), are rare. METHODS: A prospective, questionnaire-based collection of
      data on all major and minor operative procedures was undertaken at 2 hospitals in
      rural Uganda covering 4 and 3 months in 2011, respectively. Data included patient
      characteristics, indications for the interventions performed, and outcome after
      surgery. RESULTS: We recorded 2,790 operative procedures on 2,701 patients. The
      rate of major operative procedures per 100,000 population per year was 225.
      Patients undergoing major operative procedures (n = 1,051) were mostly women (n =
      923; 88%) because most interventions were performed owing to pregnancy-related
      complications (n = 747; 67%) or gynecologic conditions (n = 114; 10%). General
      operative interventions registered included herniorrhaphy (n = 103; 9%),
      exploratory laparotomy (n = 60; 5%), and appendectomy (n = 31; 3%). The POMR for
      major operative procedures was 1% (n = 14) and was greatest after exploratory
      laparotomy (13%; n = 8) and caesarean delivery (1%; n = 4). Most deaths (n = 16)
      were a result of sepsis (n = 10-11) or hemorrhage (n = 3-5). CONCLUSION: The
      volume of surgery was low relative to the size of the catchment population. The
      POMR was high. Exploratory laparotomy and caesarean section were identified as
      high-risk procedures. Increased availability of blood, improved perioperative
      monitoring, and early intervention could be part of a solution to reduce the
      POMR.

PMID- 25958071
TI  - Laparoscopic surgery performed in advanced pregnancy compared to early pregnancy.
AB  - PURPOSE: The aim of our study was to assess the clinical and obstetric outcomes
      of laparoscopic surgeries performed during advanced pregnancy compared to those
      performed in early pregnancy. METHODS: We retrospectively reviewed all cases of
      patients who underwent laparoscopic surgery during pregnancy in our institution
      between 1996 and 2013. RESULTS: We reviewed cases of 117 pregnant women who
      underwent laparoscopic surgery during the study period. There were no conversions
      to laparotomy. 71 surgeries were performed in the first trimester (group 1, mean
      gestational age 7.7 +/- 1.9 weeks) and 46 were performed in the second and third
      trimesters (group 2, mean gestational age 18.1 +/- 4.3 weeks). More patients in
      group 1 underwent surgery for suspected adnexal torsion (p < 0.001), while more
      patients in group 2 underwent surgery for presumptive cholecystitis (p = 0.014)
      and persistent ovarian mass (p = 0.011). The interval between admission and
      surgery differed significantly between the groups and was longer in group 2
      compared to group 1 (18.2 +/- 24.0 vs. 6.8 +/- 10.6 h, p = 0.001). No difference
      was found between the two groups regarding surgical complications,
      histopathological findings and pregnancy outcomes. CONCLUSION: In our experience,
      laparoscopic surgery in advanced pregnancy was found to be feasible and safe as
      in early pregnancy, without any adverse effects on pregnancy outcome.

PMID- 25958072
TI  - Enantioselective Microbial Hydroxylation as a Useful Tool in the Production of
      Jasmonate Derivatives with Aphid Deterrent Activity.
AB  - Microbial transformations of two natural compounds dihydrojasmone (1) and cis
      jasmone (3) in the growing cultures of selected twenty strains have been
      investigated. The studies have demonstrated a biocatalytic potential of tested
      microorganisms for the enantioselective hydroxylation of jasmonates. The
      substrates underwent an effective regio- and stero-selective hydroxylation at the
      allylic position in the cyclopentenone ring, and the corresponding optically pure
      keto-alcohols (2, 4) were obtained. The process of biohydroxylation depended on
      the composition of reaction medium. In the studied cultures, (+)-(R)-4
      hydroxydihydrojasmone (2) and (+) and (-)-4-hydroxyjasmone (4a, 4b) were produced
      in good yields and high enantiomeric excesses. Moreover, the introduction of the
      hydroxy group into the molecule of jasmonate ketones 1 and 3 leads to
      biologically active derivatives 2 and 4 that regulate the behaviour of aphids
      Myzus persicae by termination of their feeding. 

PMID- 25958073
TI  - Effect of Encapsulation on Viability of Pediococcus pentosaceus OZF During Its
      Passage Through the Gastrointestinal Tract Model.
AB  - The main goal of this study was to develop an improved oral delivery system for
      Pediococcus pentosaceus OZF, a promising probiotic bacterium, and to assess its
      viability under simulated gastrointestinal (GI) tract model by comparing the
      efficiency of microbiological and molecular approaches. Encapsulation was carried
      out using extrusion method and as a result, encapsulation system including 0.75 %
      lactulose, 1.8 % sodium alginate, 0.1 M CaCl2, and 5 min gelling time was shown
      to have a significantly protective effect against pH 2.0 acid stress over 3 h.
      However, completely loss of viability was exhibited by free OZF cells under
      similar conditions. To provide an additional barrier for capsules, coating
      process was investigated using different biopolymers, and the survival rates of
      free and encapsulated OZF cells upon expose to simulated GI conditions were
      detected by conventional culture techniques and propidium monoazide-quantitative
      polymerase chain reaction (PMA-qPCR) method. No significant differences between
      the biopolymers were detected, except the chitosan which leads totally 85 %
      protection and extra 25 % improvement in the survival of OZF cells compared to
      uncoated capsules. In conclusion, our findings indicated that chitosan-coated
      capsules provided an important protective effect on the viability of OZF cells
      against the GI system conditions encountered during the transit of food. In
      addition, this study was found successful in monitoring the viable OZF cells in
      capsules using PMA-qPCR method. 

PMID- 25958074
TI  - Immobilized Hydrolytic Enzymes Exhibit Antibiofilm Activity Against Escherichia
      coli at Sub-Lethal Concentrations.
AB  - The effects of two commercially available immobilized enzymes (namely the
      glycosidase pectinase and the protease subtilisin A) at sub-lethal concentrations
      were investigated in terms of their influence on biofilm genesis, on the
      composition of the biofilm matrix, and their antibiotic synergy against
      Escherichia coli biofilm, used as a model system of bacterial biofilms. The best
      antibiofilm performance of solid-supported hydrolases was obtained at the surface
      concentration of 0.022 and 0.095 U/cm(2) with a reduction of 1.2 and 2.3 log
      CFU/biofilm for pectinase and subtilisin, respectively. At these enzyme surface
      concentrations, the biocatalysts affected the structural composition of the
      biofilm matrix, impacting biofilm thickness. Finally, the immobilized hydrolases
      enhanced biofilm sensitivity to a clinically relevant concentration of the
      antibiotic ampicillin. At the final antibiotic concentration of 0.1 mg/ml, a
      reduction of 2 and 3.5 log10 units in presence of 0.022 Upectinase/cm(2) and
      0.095 Usubtilisin/cm(2) was obtained, respectively, in comparison the antibiotic
      alone. Immobilized pectinase and subtilisin at sub-lethal concentrations
      demonstrated a great potential for antibiofilm applications. 

PMID- 25958075
TI  - Anatomically and morphologically unique dark septate endophytic association in
      the roots of the Mediterranean endemic seagrass Posidonia oceanica.
AB  - Roots of terrestrial plants host a wide spectrum of soil fungi that form various
      parasitic, neutral and mutualistic associations. A similar trend is evident in
      freshwater aquatic plants and plants inhabiting salt marshes or mangroves. Marine
      vascular plants (seagrasses), by contrast, seem to lack specific root-fungus
      symbioses. We examined roots of two Mediterranean seagrasses, Posidonia oceanica
      and Cymodocea nodosa, in the northwestern Mediterranean Sea for fungal
      colonization using light and scanning and transmission electron microscopy. We
      found that P. oceanica, but not C. nodosa, is regularly associated with melanized
      septate hyphae in a manner resembling colonization by the ubiquitous dark septate
      endophytes (DSE) in roots of most terrestrial plants. P. oceanica roots were
      found to be colonized by sparse dematiaceous running hyphae as well as dense
      parenchymatous nets/hyphal sheaths on the root surface, intracellular melanized
      microsclerotia and occasionally also intra- and intercellular hyphae. The
      colonization was most prominent in the thick-walled hypodermis of the thinnest
      healthy looking roots, and the mycobiont seemed to colonize both living and dead
      host cells. Dark septate hyphae infrequently occurred also inside rhizodermal
      cells, but never colonized vascular tissues. The biological significance of this
      overlooked marine symbiosis remains unknown, but its morphology, extent,
      distribution across the NW Mediterranean Sea and absence in C. nodosa indicate an
      intriguing relationship between the dominant Mediterranean seagrass and its dark
      septate root mycobionts. 

PMID- 25958076
TI  - Neurofeedback in Hereditary Angioedema: A Single Case Study of Symptom Reduction.
AB  - Neurofeedback training was performed consisting of rewarding and encouraging 12
      15 Hz brainwaves (SMR), while simultaneously discouraging 4-7 Hz brainwaves
      (theta) and 22-30 Hz brainwaves (high beta) in the right dorsal posterior
      quadrant of the brain (T4, P4) for 20 half-hour NFB sessions to determine the
      impact on cortisol levels, DHEA-S levels, scores on the Symptom Checklist-90-R
      (SCL-90-R), the quality of life inventory, and acute attack medication usage for
      a Hereditary Angioedema patient.

PMID- 25958078
TI  - Factors influencing the Zn and Mn extraction from pyrometallurgical sludge in the
      steel manufacturing industry.
AB  - In this laboratory study, a process has been developed for selectively leaching
      zinc and manganese from pyrometallurgical sludge produced in the steel
      manufacturing industry. In the first part, the yield of Zn extraction was studied
      using four factors and four levels of the Box-Behnken response surface design.
      The optimum conditions for the step of Zn leaching were determined to be a
      sulfuric acid concentration of 0.25 mol/L, a pulp density of 10%, an extraction
      temperature of 20  degrees C, and three stages of leaching. Under such
      conditions, 75% of the Zn should be leached. For Mn leaching, the optimum
      conditions were determined to be a sulfuric acid concentration of 0.25 mol/L, a
      Na2S2O5/Mn stoichiometry of 1, a leaching time of 120 min and two leaching steps.
      In this case, 100% of the Mn should be leached. 

PMID- 25958077
TI  - Effect of arousing stimuli on circulating corticosterone and the circadian
      rhythms of luteinizing hormone (LH) surges and locomotor activity in estradiol
      treated ovariectomized (ovx+EB) Syrian hamsters.
AB  - In most proestrous hamsters, novel wheel exposure phase advances activity rhythms
      and blocks the preovulatory LH surge, which occurs 2h earlier the next day.
      Because wheel immobilization does not prevent these effects we hypothesized that
      arousal alone blocks and phase advances the LH surge. Ovariectomized (ovx)
      hamsters received a jugular vein cannula and estradiol benzoate (EB) or vehicle
      was injected sc. The next day (Day 1), at zeitgeber time (ZT) 4-5 (ZT 12 = lights
      off), after obtaining a blood sample, each hamster was exposed to constant
      darkness (DD), and either remained in her home cage or was transferred to a new
      cage and exposed to a running wheel or a 2-hour arousal paradigm. Blood samples
      were obtained in dim red light and activity was recorded hourly until ~ZT 10-11
      on Days 1 and 2. For the next 1-2 weeks, activity was monitored in DD. Plasma LH
      and corticosterone were assessed by RIA. Novel wheel exposure or arousal at ZT 4
      greatly attenuated the Day 1 LH surge in ovx+EB hamsters, and phase advanced the
      Day 2 LH surge by about 2h. In proestrous hamsters, novel wheel exposure led to a
      prolonged (>2h) increase in corticosterone levels only when LH surges were
      blocked. Phase advances in activity rhythms were enhanced by estradiol and
      arousal. The results suggest that estradiol modulates the effectiveness of non
      photic stimuli. The role of the increased activity of the hypothalamic-pituitary
      adrenal axis associated with novel wheel-induced attenuation of LH surges in
      ovx+EB hamsters remains to be determined.

PMID- 25958080
TI  - Dialysate Calcium Concentration, Mineral Metabolism Disorders, and Cardiovascular
      Disease: Deciding the Hemodialysis Bath.
AB  - Patients with end-stage kidney disease treated with dialysis are at increased
      risk to experience fractures and cardiovascular events than similar-aged people
      from the general population. The enhanced risk for these outcomes in dialysis
      patients is not completely explained by traditional risk factors for osteoporosis
      and cardiovascular disease. Mineral metabolism abnormalities are almost universal
      by the time patients require dialysis therapy, with most patients having some
      type of renal osteodystrophy and vascular calcification. These abnormalities have
      been linked to adverse skeletal and cardiovascular events. However, it has become
      clear that the treatment regimens used to modify the serum calcium, phosphate,
      and parathyroid hormone levels almost certainly contribute to the poor outcomes
      for dialysis patients. In this article, we focus on one aspect of mineral
      metabolism management; dialysate calcium concentration and the relationships
      among dialysate calcium concentrations, mineral and bone disorder, and
      cardiovascular disease in hemodialysis patients. 

PMID- 25958081
TI  - Temporal Changes in Mortality Risk by Dialysis Modality in the Australian and New
      Zealand Dialysis Population.
AB  - BACKGROUND: In most studies, home dialysis associates with greater survival than
      facility hemodialysis (HD). However, the relationship between mortality risk and
      modality can vary by era. We describe and compare changes in survival with
      facility HD, peritoneal dialysis, and home HD over a 15-year period using data
      from The Australia and New Zealand Dialysis and Transplant Registry (ANZDATA).
      STUDY DESIGN: An observational inception cohort study, using Cox proportional
      hazards and competing-risks regression. SETTING & PARTICIPANTS: All adult
      patients initiating renal replacement therapy in Australia and New Zealand since
      March 31, 1998, followed up to December 31, 2012. PREDICTOR: Era at dialysis
      inception (1998-2002, 2003-2007, and 2008-2012). We adjusted for time-varying
      dialysis modality and comorbid conditions, demographics, initial state/country of
      treatment, late referral for nephrology care, primary kidney disease, and kidney
      function at dialysis inception. OUTCOMES: Patient mortality. RESULTS: Survival on
      dialysis therapy has improved despite increasing patient comorbid conditions.
      Compared to 1998 to 2002, there has been a 21% reduction in mortality for those
      on facility HD therapy, a 27% reduction for those on peritoneal dialysis therapy,
      and a 49% reduction for those on home HD therapy. LIMITATIONS: Potential for
      residual confounding from limited collection of comorbid conditions; analyses
      lack data for blood pressure, fluid volume status, socioeconomics, medication,
      and biochemical parameters. CONCLUSIONS: Our study indicates that outcomes on
      dialysis therapy are improving with time and that this improvement is most marked
      with home dialysis modalities, especially home HD. This might be the result of
      better dialysis care (eg, improving predialysis care and more appropriate
      selection of patients for home dialysis). Other contributing factors are
      possible, such as improvements in general care of patient comorbid conditions and
      improvements in dialysis technology, although further research is needed to
      clarify these issues.

PMID- 25958082
TI  - Ectopic expression of GroEL from Xenorhabdus nematophila in tomato enhances
      resistance against Helicoverpa armigera and salt and thermal stress.
AB  - The GroEL homolog XnGroEL protein of Xenorhabdus nematophila belongs to a highly
      conserved family of molecular chaperones/heat shock proteins (Hsps). XnGroEL was
      shown to possess oral insecticidal activity against a major crop pest Helicoverpa
      armigera. Under normal conditions, the Hsps/chaperones facilitate folding,
      assembly, and translocation of cellular proteins, while in stress conditions they
      protect proteins from denaturation. In this study, we describe generation of
      transgenic tomato plants overexpressing insecticidal XnGroEL protein and their
      tolerance to biotic and abiotic stresses. Presence of XnGroEL in the transgenic
      tomato lines conferred resistance against H. armigera showing 100% (p <= 0.001)
      mortality of neonates. In addition, XnGroEL provided thermotolerance and
      protection against high salt concentration to the tomato plants. Expression of
      XnGroEL minimized photo-oxidation of chlorophyll and reduced oxidative damage of
      cell membrane system of the plants under heat and salt stress. The enhanced
      tolerance to abiotic stresses correlated with increase in the anti-oxidative
      enzyme activity and reduced H2O2 accumulation in transgenic tomato plants. The
      variety of beneficial properties displayed by XnGroEL protein provides an
      opportunity for value addition and improvement of crop productivity.

PMID- 25958084
TI  - LH peak and ovulation after two different estrus synchronization treatments in
      buffalo cows in the daylight-lengthening period.
AB  - The aim of this study was to determine the timing of ovulation in relation to the
      LH peak after synchronization using PRID or Ovsynch protocols, to assess the
      effects of the period of treatment on these parameters and to provide information
      concerning how to use the two main protocols for fixed-time artificial
      insemination in buffalo. Forty-eight lactating Italian Mediterranean buffalo cows
      were used. The buffaloes were treated in various periods as follows: February to
      March (n = 12 PRID, n = 12 Ovsynch), end of the breeding season, May to June (n =
      12 PRID, n = 12 Ovsynch), beginning of low-breeding season according to Italian
      environmental conditions. To determine the LH, blood samples were taken at 4-hour
      intervals, starting 24 hours from PRID removal (PRID group) or 12 hours from
      (PGF2alpha) injection (Ovsynch group) up to 108 hours. The ovaries were monitored
      by transrectal ultrasonography to verify ovulation. The LH-ovulation interval was
      similar in both groups (30.10 +/- 1.05 and 32.77 +/- 1.15 hours, respectively, in
      PRID and Ovsynch group). In the PRID group, the timing of ovulation in relation
      to device removal was 76.83 +/- 3.65 hours with a high level of variability among
      the animals. In the Ovsynch group, we observed a better synchronization of LH
      peaks and ovulations, and the timing of ovulation in relation to the last GnRH
      injection was 35.67 +/- 1.15 hours. The percentage of animals reaching the LH
      peak and ovulation was lower (P <= 0.05) in May to June (respectively 75.0% and
      54.1%) compared to February to March (respectively 95.8% and 83.3%), indicating a
      reduction of hypothalamus-pituitary responsiveness to the synchronization
      treatments in the daylight-lengthening period.

PMID- 25958085
TI  - Reevaluation and evolution of the simulated physiological oocyte maturation
      system.

PMID- 25958083
TI  - The incidence of eating disorders in a Danish register study: Associations with
      suicide risk and mortality.
AB  - Our aim was to characterize the incidence rates and cumulative incidence of
      anorexia nervosa (AN), bulimia nervosa (BN), and eating disorder not otherwise
      specified (EDNOS), and examine associations among eating disorder diagnoses,
      suicide attempts, and mortality. Individuals born in Denmark between 1989 and
      2006 were included (N = 966,141, 51.3% male). Eating disorders diagnoses (AN,
      broad AN, BN, EDNOS) were drawn from the Danish Psychiatric Central Research
      Register (PCRR) and Danish National Patient Register (NPR). Suicide attempts and
      deaths were captured in the NPR, the PCRR, and the Danish Civil Registration
      System (CRS). In females, AN had a peak hazard at approximately age 15 years, BN
      at 22 years, and EDNOS had an extended peak that spanned 18 years-22 years.
      Eating disorder diagnoses predicted a significantly higher hazard for death and
      suicide attempt compared with the referent of individuals with no eating
      disorders. In males, peak hazard for diagnosis was earlier than in females. The
      present study represents one of the largest and longest studies of eating
      disorder incidence and suicide attempts and death in both females and males.
      Eating disorders are accompanied by increased hazard of suicide attempts and
      death even in young adults. 

PMID- 25958079
TI  - The Phosphate Binder Ferric Citrate and Mineral Metabolism and Inflammatory
      Markers in Maintenance Dialysis Patients: Results From Prespecified Analyses of a
      Randomized Clinical Trial.
AB  - BACKGROUND: Phosphate binders are the cornerstone of hyperphosphatemia management
      in dialysis patients. Ferric citrate is an iron-based oral phosphate binder that
      effectively lowers serum phosphorus levels. STUDY DESIGN: 52-week, open-label,
      phase 3, randomized, controlled trial for safety-profile assessment. SETTING &
      PARTICIPANTS: Maintenance dialysis patients with serum phosphorus levels >=6.0
      mg/dL after washout of prior phosphate binders. INTERVENTION: 2:1 randomization
      to ferric citrate or active control (sevelamer carbonate and/or calcium acetate).
      OUTCOMES: Changes in mineral bone disease, protein-energy wasting/inflammation,
      and occurrence of adverse events after 1 year. MEASUREMENTS: Serum calcium,
      intact parathyroid hormone, phosphorus, aluminum, white blood cell count,
      percentage of lymphocytes, serum urea nitrogen, and bicarbonate. RESULTS: There
      were 292 participants randomly assigned to ferric citrate, and 149, to active
      control. Groups were well matched. For mean changes from baseline, phosphorus
      levels decreased similarly in the ferric citrate and active control groups (
      2.04+/-1.99 [SD] vs -2.18+/-2.25 mg/dL, respectively; P=0.9); serum calcium
      levels increased similarly in the ferric citrate and active control groups
      (0.22+/-0.90 vs 0.31+/-0.95 mg/dL; P=0.2). Hypercalcemia occurred in 4
      participants receiving calcium acetate. Parathyroid hormone levels decreased
      similarly in the ferric citrate and active control groups (-167.1+/-399.8 vs 
      152.7+/-392.1 pg/mL; P=0.8). Serum albumin, bicarbonate, serum urea nitrogen,
      white blood cell count and percentage of lymphocytes, and aluminum values were
      similar between ferric citrate and active control. Total and low-density
      lipoprotein cholesterol levels were lower in participants receiving sevelamer
      than those receiving ferric citrate and calcium acetate. Fewer participants
      randomly assigned to ferric citrate had serious adverse events compared with
      active control. LIMITATIONS: Open-label study, few peritoneal dialysis patients.
      CONCLUSIONS: Ferric citrate was associated with similar phosphorus control
      compared to active control, with similar effects on markers of bone and mineral
      metabolism in dialysis patients. There was no evidence of protein-energy
      wasting/inflammation or aluminum toxicity, and fewer participants randomly
      assigned to ferric citrate had serious adverse events. Ferric citrate is an
      effective phosphate binder with a safety profile comparable to sevelamer and
      calcium acetate.

PMID- 25958086
TI  - Assessment of heavy metal contamination in water and sediments of Trepca and
      Sitnica rivers, Kosovo, using pollution indicators and multivariate cluster
      analysis.
AB  - The concentrations of As, Cd, Cr, Co, Cu, Ni, Pb, and Zn in water and sediment
      samples from Trepca and Sitnica rivers were determined to assess the level of
      contamination. Six water and sediment samples were collected during the period
      from April to July 2014. Most of the water samples was found within the European
      and Kosovo permissible limits. The highest concentration of As, Cd, Pb, and Zn
      originates primarily from anthropogenic sources such discharge of industrial
      water from mining flotation and from the mine waste eroded from the river banks.
      Sediment contamination assessment was carried out using the pollution indicators
      such as contamination factor (CF), degree of contamination (Cd), modified degree
      of contamination (mCd), pollution load index (PLI), and geo-accumulation index
      (Igeo). The CF values for the investigated metals indicated a high contaminated
      nature of sediments, while the Cd values indicated a very high contamination
      degree of sediments. The mCd values indicate a high degree of contamination of
      Sitnica river sediment to ultrahigh degree of contamination of Trepca river
      sediment. The PLI values ranged from 1.89 to 14.1 which indicate that the heavy
      metal concentration levels in all investigated sites exceeded the background
      values and sediment quality guidelines. The average values of Igeo revealed the
      following ranking of intensity of heavy metal contamination of the Trepca and
      Sitnica river sediments: Cd > As > Pb > Zn > Cu > Co > Cr > Ni. Cluster analysis
      suggests that As, Cd, Cr, Co, Cu, Ni, Pb, and Zn are derived from anthropogenic
      sources, particularly discharges from mining flotation and erosion form waste
      from a zinc mine plant. In order to protect the sediments from further
      contamination, the designing of a monitoring network and reducing the
      anthropogenic discharges are suggested.

PMID- 25958087
TI  - Distribution of natural and artificial radioactivity in soils, water and tuber
      crops.
AB  - Activity concentrations of radionuclides in water, soil and tuber crops of a
      major food-producing area in Ghana were investigated. The average gross alpha and
      beta activities were 0.021 and 0.094 Bq/L, respectively, and are below the
      guidelines for drinking water and therefore not expected to pose any significant
      health risk. The average annual effective dose due to ingestion of radionuclide
      in water ranged from 20.08 to 53.45 MUSv/year. The average activity concentration
      of (238)U, (232)Th, (40)K and (137)Cs in the soil from different farmlands in the
      study area was 23.19, 31.10, 143.78 and 2.88 Bq/kg, respectively, which is lower
      than world averages. The determined absorbed dose rate for the farmlands ranged
      from 23.63 to 50.51 nGy/year, which is within worldwide range of 18 to 93
      nGy/year. The activity concentration of (238)U, (232)Th, (40)K and (137)Cs in
      cassava ranges from 0.38 to 6.73, 1.82 to 10.32, 17.65 to 41.01 and 0.38 to 1.02
      Bq/kg, respectively. Additionally, the activity concentration of (238)U, (232)Th,
      (40)K and (137)Cs in yam also ranges from 0.47 to 4.89, 0.93 to 5.03, 14.19 to
      35.07 and 0.34 to 0.89 Bq/kg, respectively. The average concentration ratio for
      (238)U, (232)Th and (40)K in yam was 0.12, 0.11 and 0.17, respectively, and in
      cassava was 0.11, 0.12 and 0.2, respectively. None of the radioactivity is
      expected to cause significant health problems to human beings.

PMID- 25958088
TI  - Psychiatric symptoms in frontotemporal dementia: epidemiology, phenotypes, and
      differential diagnosis.
AB  - Frontotemporal dementia (FTD) is the most frequently occurring dementia in the
      presenile population. Despite epidemiologic data showing that patients with FTD
      may have experienced previous psychiatric disorders and that patients with
      psychotic disorders may develop dementia more often than expected in the
      nonaffected population, the overlap between these two conditions has been
      underestimated. Nevertheless, the identification in recent years of several
      genetic causes of FTD associated with heterogeneous and atypical presentations,
      including pure psychiatric symptoms, has shifted scientific interest back to
      obtaining a better understanding of common mechanisms between FTD and psychotic
      disorders. We review the current knowledge of the FTD spectrum and common
      features shared by FTD and some psychiatric diseases, starting from Pick's
      clinical description of the disease, moving toward pathogenic aspects of the
      disease and genetic causes and associated phenotypes, and finishing with analysis
      of crossing borders between FTD and psychiatric disorders (mainly represented by
      schizophrenia and bipolar spectrum disorders) in clinical practice in terms of
      overlapping symptoms, differential diagnosis, comorbidity, and treatment issues. 

PMID- 25958089
TI  - Talin is required to position and expand the luminal domain of the Drosophila
      heart tube.
AB  - Fluid- and gas-transporting tubular organs are critical to metazoan development
      and homeostasis. Tubulogenesis involves cell polarization and morphogenesis to
      specify the luminal, adhesive, and basal cell domains and to establish an open
      lumen. We explore a requirement for Talin, a cytoplasmic integrin adapter, during
      Drosophila melanogaster embryonic heart tube development. Talin marks the
      presumptive luminal domain and is required to orient and develop an open luminal
      space within the heart. Genetic analysis demonstrates that loss of zygotic or
      maternal-and-zygotic Talin disrupts heart cell migratory dynamics, morphogenesis,
      and polarity. Talin is essential for subsequent polarization of luminal
      determinants Slit, Robo, and Dystroglycan as well as stabilization of
      extracellular and intracellular integrin adhesion factors. In the absence of
      Talin function, mini-lumens enriched in luminal factors form in ectopic
      locations. Rescue experiments performed with mutant Talin transgenes suggest that
      actin-binding is required for normal lumen formation, but not for initial heart
      cell polarization. We propose that Talin provides instructive cues to position
      the luminal domain and coordinate the actin cytoskeleton during Drosophila heart
      lumen development. 

PMID- 25958090
TI  - FGF signaling supports Drosophila fertility by regulating development of ovarian
      muscle tissues.
AB  - The thisbe (ths) gene encodes a Drosophila fibroblast growth factor (FGF), and
      mutant females are viable but sterile suggesting a link between FGF signaling and
      fertility. Ovaries exhibit abnormal morphology including lack of epithelial
      sheaths and muscle tissues that surround ovarioles. Here we investigated how FGF
      influences Drosophila ovary morphogenesis and identified several roles. Heartless
      (Htl) FGF receptor was found to be expressed within somatic cells at the larval
      and pupal stages, and phenotypes were uncovered using RNAi. Differentiation of
      terminal filament cells was affected, but this effect did not alter the ovariole
      number. In addition, proliferation of epithelial sheath progenitors, the apical
      cells, was decreased in both htl and ths mutants, while ectopic expression of the
      Ths ligand led to these cells' over-proliferation suggesting that FGF signaling
      supports ovarian muscle sheath formation by controlling apical cell number in the
      developing gonad. Additionally, live imaging of adult ovaries was used to show
      that htl RNAi mutants, hypomorphic mutants in which epithelial sheaths are
      present, exhibit abnormal muscle contractions. Collectively, our results
      demonstrate that proper formation of ovarian muscle tissues is regulated by FGF
      signaling in the larval and pupal stages through control of apical cell
      proliferation and is required to support fertility. 

PMID- 25958091
TI  - Heterozygous expression of the oncogenic Pik3ca(H1047R) mutation during murine
      development results in fatal embryonic and extraembryonic defects.
AB  - The phosphoinositide 3-kinase (PI3K)/AKT signalling pathway regulates many
      cellular functions including proliferation, migration, survival and protein
      synthesis. Somatic mutations in PIK3CA, the gene encoding the p110alpha catalytic
      subunit of PI3K enzyme, are commonly associated with many human cancers as well
      as recently being implicated in human overgrowth syndromes. However, it is not
      clear if such mutations can be inherited through the germline. We have used a
      novel mouse model with Cre recombinase (Cre)-conditional knock-in of the common
      H1047R mutation into the endogenous Pik3ca gene. Heterozygous expression of the
      Pik3ca(H1047R) mutation in the developing mouse embryo resulted in failed
      'turning' of the embryo and disrupted vascular remodelling within the embryonic
      and extraembryonic tissues, leading to lethality prior to E10. As vascular
      endothelial growth factor A (VEGF-A) signalling was disrupted in these embryos,
      we used Cre under the control of the Tie2 promoter to target the Pik3ca(H1047R)
      mutation specifically to endothelial cells. In these embryos turning occurred
      normally but the vascular remodelling defects and embryonic lethality remained,
      likely as a result of endothelial hyperproliferation. Our results confirm the
      lethality associated with heterozygous expression of the Pik3ca(H1047R) mutation
      during development and likely explain the lack of inherited germline PIK3CA
      mutations in humans. 

PMID- 25958092
TI  - Evaluation of three headspace sorptive extraction coatings for the determination
      of volatile terpenes in honey using gas chromatography-mass spectrometry.
AB  - Headspace sorptive extraction (HSSE) was used to preconcentrate seven
      monoterpenes (eucalyptol, linalool, menthol, geraniol, carvacrol, thymol and
      eugenol) for separation by gas chromatography and mass spectrometry (GC-MS).
      Three commercially available coatings for the stir bars, namely
      Polydimethylsiloxane (PDMS), polyacrilate (PA) and Ethylene glycol-silicone (EG
      Silicone), were tested, and the influential parameters both in the adsorption and
      the thermal desorption steps were optimized. PDMS provided the best sensitivity
      for linalool, geraniol, menthol and eucalyptol, whereas EG-Silicone was best for
      extracting the phenolic monoterpenes studied. Considering the average obtained
      slopes from all compounds, PDMS pointed as the best option, and the analytical
      characteristics for the HSSE-TD-GC-MS method using this coating were obtained.
      Quantification of the samples was carried out by matrix-matched calibration using
      a synthetic honey. Detection limits ranged between 0.007 and 0.032 ng g(-1),
      depending on the compound. Twelve honey samples of different floral origins were
      analyzed using the HSSE-GC-MS method, the analytes being detected at
      concentrations up to 64 ng g(-1).

PMID- 25958093
TI  - A critical evaluation of an asymmetrical flow field-flow fractionation system for
      colloidal size characterization of natural organic matter.
AB  - Colloidal retention characteristics, recovery and size distribution of model
      macromolecules and natural dissolved organic matter (DOM) were systematically
      examined using an asymmetrical flow field-flow fractionation (AFlFFF) system
      under various membrane size cutoffs and carrier solutions. Polystyrene sulfonate
      (PSS) standards with known molecular weights (MW) were used to determine their
      permeation and recovery rates by membranes with different nominal MW cutoffs
      (NMWCO) within the AFlFFF system. Based on a >=90% recovery rate for PSS
      standards by the AFlFFF system, the actual NMWCOs were determined to be 1.9 kDa
      for the 0.3 kDa membrane, 2.7 kDa for the 1 kDa membrane, and 33 kDa for the 10
      kDa membrane, respectively. After membrane calibration, natural DOM samples were
      analyzed with the AFlFFF system to determine their colloidal size distribution
      and the influence from membrane NMWCOs and carrier solutions. Size partitioning
      of DOM samples showed a predominant colloidal size fraction in the <5 nm or <10
      kDa size range, consistent with the size characteristics of humic substances as
      the main terrestrial DOM component. Recovery of DOM by the AFlFFF system, as
      determined by UV-absorbance at 254 nm, decreased significantly with increasing
      membrane NMWCO, from 45% by the 0.3 kDa membrane to 2-3% by the 10 kDa membrane.
      Since natural DOM is mostly composed of lower MW substances (<10 kDa) and the
      actual membrane cutoffs are normally larger than their manufacturer ratings, a
      0.3 kDa membrane (with an actual NMWCO of 1.9 kDa) is highly recommended for
      colloidal size characterization of natural DOM. Among the three carrier
      solutions, borate buffer seemed to provide the highest recovery and optimal
      separation of DOM. Rigorous calibration with macromolecular standards and
      optimization of system conditions are a prerequisite for quantifying colloidal
      size distribution using the flow field-flow fractionation technique. In addition,
      the coupling of AFlFFF with fluorescence EEMs could provide new insights into DOM
      heterogeneity in different colloidal size fractions.

PMID- 25958094
TI  - In search of a role of REM sleep in memory formation.

PMID- 25958095
TI  - Axially vascularised mandibular constructs: Is it time for a clinical trial?
AB  - Applying regenerative therapies in the field of cranio-maxillofacial
      reconstruction has now become a daily practice. However, regeneration of
      challenging or irradiated bone defects following head and neck cancer is still
      far beyond clinical application. As the key factor for sound regeneration is the
      development of an adequate vascular supply for the construct, the current
      modalities using extrinsic vascularization are incapable of regenerating such
      complex defects. Our group has recently introduced the intrinsic axial
      vascularization technique to regenerate mandibular defects using the
      arteriovenous loop (AVL). The technique has shown promising results in terms of
      efficient vascularization and bone regeneration at the preclinical level. In this
      article, we have conducted a narrative literature review about using the AVL to
      vascularize tissue-engineering constructs at the preclinical level. We have also
      conducted a systematic literature review about applying the technique of axial
      vascularization in the field of craniofacial regeneration. The versatility of the
      technique and the possible challenges are discussed, and a suggested protocol for
      the first clinical trial applying the AVL technique for mandibular reconstruction
      is also presented. 

PMID- 25958097
TI  - Surgical management of upgaze diplopia in patients after posttraumatic orbital
      floor reconstruction.
AB  - OBJECTIVE: The most common complication of otherwise successful reconstructive
      surgery of a fractured orbital floor is persistent diplopia. For patients with
      troublesome double vision in upgaze, a reasonable solution is offered by
      strabismus surgery. The aim of our study is to examine the results of extraocular
      muscle surgery in cases of diplopia that persisted in upgaze after posttraumatic
      orbital floor reconstruction. MATERIAL AND METHODS: In this study we present a
      retrospective series of 24 patients with troublesome vertical diplopia in upgaze.
      In all cases, the surgery consisted of a posterior fixation suture placement on
      the contralateral superior rectus muscle with or without its recession. Full
      orthoptic examination was conducted before and 3 months after the surgery.
      RESULTS: Postoperatively 19 patients (79%) were diplopia free and 6 (21%) had
      vertical diplopia in extreme upgaze. The field of binocular single vision
      improved threefold. None of the patients reported diplopia in the primary
      position or in any position other than upgaze. CONCLUSION: Vertical incomitant
      strabismus and diplopia in upgaze persisting after orbital reconstructive surgery
      may be corrected surgically. Contralateral posterior fixation of the superior
      rectus muscle, with or without its recession, appears to be an effective
      procedure for use in these patients.

PMID- 25958096
TI  - A randomized controlled trial comparing two techniques for unilateral cleft lip
      and palate: Growth and speech outcomes during mixed dentition.
AB  - OBJECTIVE: To study the growth and speech outcomes in children who were operated
      on for unilateral cleft lip and palate (UCLP) by a single surgeon using two
      different treatment protocols. MATERIAL AND METHODS: A total of 200 consecutive
      patients with nonsyndromic UCLP were randomly allocated to two different
      treatment protocols. Of the 200 patients, 179 completed the protocol. However,
      only 85 patients presented for follow-up during the mixed dentition period (7-10
      years of age). The following treatment protocol was followed. Protocol 1
      consisted of the vomer flap (VF), whereby patients underwent primary lip nose
      repair and vomer flap for hard palate single-layer closure, followed by soft
      palate repair 6 months later; Protocol 2 consisted of the two-flap technique
      (TF), whereby the cleft palate (CP) was repaired by two-flap technique after
      primary lip and nose repair. GOSLON Yardstick scores for dental arch relation,
      and speech outcomes based on universal reporting parameters, were noted. RESULTS:
      A total of 40 patients in the VF group and 45 in the TF group completed the
      treatment protocols. The GOSLON scores showed marginally better outcomes in the
      VF group compared to the TF group. Statistically significant differences were
      found only in two speech parameters, with better outcomes in the TF group.
      CONCLUSIONS: Our results showed marginally better growth outcome in the VF group
      compared to the TF group. However, the speech outcomes were better in the TF
      group.

PMID- 25958098
TI  - First trimester gestational diabetes screening - Change in incidence and
      pharmacotherapy need.
AB  - AIMS: Adopting recommendations of the International Association of Diabetes in
      Pregnancy Study Groups (IADPSG) and the California Diabetes and Pregnancy
      Program, our institution implemented early gestational diabetes (GDM) screening.
      Our objective was to compare GDM diagnosis rates using the standard two-step
      approach versus early screening, and secondarily to compare pharmacotherapy needs
      and perinatal outcomes. METHODS: This retrospective study included singleton
      pregnancies diagnosed between 7/2010 and 6/2012. Two cohorts were compared; those
      diagnosed via two-step screening versus early screening diagnosis: HbA1c>=5.7%
      (39 mmol/mol) or fasting plasma glucose (FPG)>=92 mg/dL at <=24 weeks gestation,
      or an abnormal 2-h oral glucose tolerance test (GTT) between 24 and 28 weeks. We
      calculated the rate of diagnosis, analyzed the need for pharmacotherapy, and
      reviewed neonatal outcomes. RESULTS: A total of 2652 patients were screened. GDM
      was diagnosed in 5.3% with two-step screening and 9.4% with early screening. Of
      those diagnosed via early screening with HbA1c, FPG, or both HbA1c and FPG,
      49.2%, 66.7%, and 78.9% respectively required pharmacotherapy. In contrast, of
      those diagnosed with a 2-h GTT, 30.6% required pharmacotherapy (p<0.001). When
      controlling for confounders in a multivariable regression, BMI is most predictive
      of medication requirements (aOR 1.13, 95% CI 1.08-1.18, p<0.001). There were no
      differences in mean birth weight (3240+/-619 g vs. 3179+/-573 g, p=0.51) and
      macrosomia rates (7% vs. 2.5%, p=0.12). CONCLUSION: Implementing early screening
      nearly doubled the incidence of GDM. Patients with early screening had a greater
      need for pharmacotherapy, but BMI was the best predictor of this outcome. There
      was no significant difference in neonatal outcomes.

PMID- 25958099
TI  - Novel biomarkers of cardiometabolic risk are associated with plasma glucose
      within non-diabetic range. The Brazilian Longitudinal Study of Adult Health -
      ELSA-Brasil.
AB  - Abnormal glucose metabolism preceding overt diabetes is associated with increased
      cardiovascular risk. Whether novel biomarkers are useful to identify this
      condition is unclear. The objective was to investigate associations of biomarkers
      of atherogenesis with plasma glucose within non-diabetic range. 998 participants
      (35-54 years) of the Brazilian Longitudinal Study of Adult Health without
      diabetes or cardiovascular disease were classified as normal glucose tolerance
      (NGT), impaired fasting glycemia (IFG) and impaired glucose tolerance (IGT).
      Traditional risk factors and markers of atherogenesis were evaluated among groups
      and across plasma glucose concentrations. IFG and IGT had worse profile
      considering traditional cardiovascular risk factors than the NGT group, although
      these values were within the reference range. NGT, IFG and IGT groups differed
      (medians and interquartile intervals) regarding transforming growth factor-beta1
      [12.2 (6.4-22.3), 16.8 (8.4-26.5), and 15.5 (8.0-26.1)pg/mL, p<0.05], C-reactive
      protein [1.1 (0.6-2.9), 1.2 (0.6-2.7), and 1.4 (0.8-3.7)ng/mL, p<0.001] and
      monocyte chemoattractant protein-1 [35.9 (21.2-57.8), 32.2 (18.7-55.8), and 34.1
      (18.6-52.4)pg/mL, p<0.05]. TGF-beta1 and E-selectin concentrations increased
      while MCP-1 decreased across quartiles of fasting plasma glucose. C-reactive
      protein increased with increments in 2-h plasma glucose. In linear regression,
      TGF-beta1 was independently associated with fasting plasma glucose, and C
      reactive protein with 2-h plasma glucose after adjustments. In conclusion,
      association of TGF-beta1, E-selectin, C-reactive protein and MCP-1 with slight
      elevations in glycemia may be anticipating alterations in traditional
      cardiovascular risk factors. Independent association of TGF-beta1 with plasma
      glucose suggests that this may be useful to identifying atherogenic process,
      deserving further investigation on the prediction of cardiovascular outcomes. 

PMID- 25958101
TI  - The palliative treatment with intrapleural streptokinase in patients with
      multiloculated malignant pleural effusion: a double-blind, placebo-controlled,
      randomized study.
AB  - Expansion of the lung is necessary for successful pleurodesis therapy in patients
      with malignant pleural effusion (MPE). However, this is often impossible in
      multiloculated MPEs. The aim of this study was to investigate the effect of the
      fibrinolytic agent, streptokinase, on pleurodesis therapy used in the management
      of multiloculated MPE. Forty patients with multiloculated MPEs were randomly
      assigned to two groups: fibrinolytic and control. In the fibrinolytic group,
      250,000 IU of streptokinase in 50 ml saline was applied into the pleural space at
      24-36-48-60 h after opening a tube thoracostomy. In the control group, the same
      procedure was carried out using only 50 ml saline solution. Both groups were
      compared based on the following: (1) volume of pleural drainage at 24-48, 48-72,
      and 24-72 h, (2) chest computer tomography images before and after therapy, (3)
      dyspnea symptoms after therapy, and (4) recurrence rate. The mean drainage
      volumes for the fibrinolytic and control groups were 493 and 248 cc at 24-48 h,
      446 and 198 cc at 48-72 h, and 939 and 446 cc at 24-72 h (P < 0.001). Comparison
      of the two groups by computer tomography revealed that 17 patients (85 %) in the
      fibrinolytic group had greater than 40 % improvement, whereas only 7 patients (35
      %) in the control group had the same degree of improvement (P = 0.001). The
      dyspnea symptoms disappeared in 90 % of the patients in the fibrinolytic group
      and in 55 % of the patients in the control group (P = 0.03). Recurrence rate was
      11 % in fibrinolytic group and 45 % in control group (P = 0.07). Streptokinase is
      a reliable treatment option in obtaining effective pleural drainage and
      increasing lung expansion in patients with multiloculated MPE.

PMID- 25958100
TI  - Septic arthritis of the facet joint.
AB  - OBJECTIVE: Septic arthritis of the facet joint is a rare clinical entity. We
      report 11 cases of facet joint infections diagnosed in our institution. PATIENTS
      AND METHOD: Patients were identified via the computerized patients record (PMSI).
      Their features were collected and compared with published data. RESULTS: The
      clinical symptoms are similar to those of infectious spondylodiscitis: back pain
      with stiffness (11/11), fever (9/11), radicular pain (5/11), and asthenia. Ten
      patients presented with lumbar infection and 1 with dorsal infection. An
      inflammatory syndrome was observed in every case. A rapid access to spine MRI
      allowed making the diagnosis in every case, and assessing a potential extension
      of infection (epidural extension 5/11, paraspinal extension 5/11). Blood culture
      (8/11) or culture of spinal samples allowed identifying the causative bacterium
      in every case and adapting the antibiotic treatment. The bacteria identified in
      our series were different from previously reported ones, with less staphylococci.
      The origin of the infection was found in 4 cases. Another localization of
      infection was observed in 4 cases. The outcome was favorable with medical
      treatment in 10 cases. An abscess was surgically drained in 1 case. None of our
      patients presented with neurological complications, probably because of the rapid
      diagnosis. CONCLUSION: Assessing the facet joint is essential in case of
      inflammatory back pain, and the radiologist must be asked to perform this
      examination.

PMID- 25958102
TI  - Raoultella planticola peritonitis in a patient on continuous ambulatory
      peritoneal dialysis.
AB  - A 65-year-old man on continuous ambulatory peritoneal dialysis was admitted with
      peritonitis. Empirical antibiotic therapy was initiated, and Raoultella
      planticola was identified in the peritoneal fluid culture. We treated the patient
      with intraperitoneally administered ciprofloxacin and ceftazidime according to
      the antibiotic susceptibility. His condition improved, and he was well treated
      with a 2-week antibiotic course.

PMID- 25958103
TI  - Sexual size and shape dimorphism and allometric scaling patterns in head traits
      in the New Zealand common gecko Woodworthia maculatus.
AB  - Sexual dimorphism in shape and size is widespread across animal taxa and arises
      when natural or sexual selection operates differently on the sexes. Male and
      female common geckos (Woodworthia maculatus; formerly Hoplodactylus maculatus) in
      New Zealand do not appear to experience different viability selection pressure,
      nor do males appear to be under intense pre-copulatory sexual selection. It was
      therefore predicted that this species would be sexually monomorphic with regard
      to body size and the size and shape of the head. In line with the prediction,
      there was no sexual difference in head width, depth, or length or in lateral head
      shape. However, contrary to prediction, males had a larger body and lateral head
      size than females. This study suggests that males, at least on Maud Island, NZ,
      might be under stronger pre-copulatory sexual selection than previously
      recognized and thus have evolved larger heads (i.e. lateral head size) for use in
      male combat for females. Allometric scaling patterns do not differ between the
      sexes and suggest that head width and depth are under directional selection
      whereas lateral head size is under stabilizing selection. Diet ecology - an agent
      of natural selection common to both sexes - is likely largely responsible for the
      observed patterns of head size and shape and the lack of sexual dimorphism in
      them. 

PMID- 25958104
TI  - Ultrastructural and biochemical characterization of mechanically adaptable
      collagenous structures in the edible sea urchin Paracentrotus lividus.
AB  - The viscoelastic properties of vertebrate connective tissues rarely undergo
      significant changes within physiological timescales, the only major exception
      being the reversible destiffening of the mammalian uterine cervix at the end of
      pregnancy. In contrast to this, the connective tissues of echinoderms (sea
      urchins, starfish, sea cucumbers, etc.) can switch reversibly between stiff and
      compliant conditions in timescales of around a second to minutes. Elucidation of
      the molecular mechanism underlying such mutability has implications for the
      zoological, ecological and evolutionary field. Important information could also
      arise for veterinary and biomedical sciences, particularly regarding the
      pathological plasticization or stiffening of connective tissue structures. In the
      present investigation we analyzed aspects of the ultrastructure and biochemistry
      in two representative models, the compass depressor ligament and the peristomial
      membrane of the edible sea urchin Paracentrotus lividus, compared in three
      different mechanical states. The results provide further evidence that the
      mechanical adaptability of echinoderm connective tissues does not necessarily
      imply changes in the collagen fibrils themselves. The higher glycosaminoglycan
      (GAG) content registered in the peristomial membrane with respect to the compass
      depressor ligament suggests a diverse role of these molecules in the two mutable
      collagenous tissues. The possible involvement of GAG in the mutability phenomenon
      will need further clarification. During the shift from a compliant to a standard
      condition, significant changes in GAG content were detected only in the compass
      depressor ligament. Similarities in terms of ultrastructure (collagen fibrillar
      assembling) and biochemistry (two alpha chains) were found between the two models
      and mammalian collagen. Nevertheless, differences in collagen immunoreactivity,
      alpha chain migration on SDS-PAGE and BLAST alignment highlighted the uniqueness
      of sea urchin collagen with respect to mammalian collagen. 

PMID- 25958105
TI  - Perception of secondary conditions in adults with spina bifida and impact on
      daily life.
AB  - BACKGROUND: Spina bifida is a congenital defect of the neural tube resulting in
      motor and sensory disruption. Persons with spina bifida can also experience
      executive function impairments. Secondary conditions are physical, medical,
      cognitive, emotional, or psychosocial consequences to which persons with
      disabilities are more susceptible. Our experience suggested clinicians
      underappreciate the presence and impact of secondary conditions in adults with
      spina bifida because they do not specifically ask for this information.
      OBJECTIVE: Describe the presence and impact of secondary conditions on daily
      life, as perceived by adults with spina bifida. METHODS: A clinic-based sample
      was recruited from the active patient population of an adult specialty center for
      spina bifida-related care. All subjects were verbally administered a survey
      developed through literature review and clinical experience of the researchers.
      The survey measured the presence and perceived impact of secondary conditions.
      Recruitment and survey data collection occurred over a 6-month period to maximize
      age representation. Survey data were stratified by age, gender and lesion level
      for analysis. RESULTS: Seventy-two respondents completed the survey. Pain was
      commonly reported, along with pressure ulcers, bowel & bladder concerns,
      depression, sleep disturbance, and limited social and community participation. No
      significant relationships were found between the presence or perceived impact of
      secondary conditions and age, gender or level of lesion. CONCLUSIONS: Secondary
      conditions in spina bifida are present by early adulthood. Identifying these
      conditions during clinical encounters requires specific rather than general
      questions. Future study should evaluate earlier initiation of preventative
      measures by pediatric providers.

PMID- 25958106
TI  - IR-spectroscopic characterization of an elongated OmpG mutant.
AB  - OmpG is a nonselective, pH dependent outer membrane protein from Escherichia
      coli. It consists of 281 residues, forming a 14-stranded beta-sheet structure. In
      this study, OmpG is extended by 38 amino acids to produce a 16-stranded beta
      barrel (OmpG-16S). The resulting protein is investigated by IR-spectroscopy. The
      secondary structure, pH-dependent opening/closing mechanism, buffer accessibility
      and thermal stability of OmpG-16S are compared to OmpG-WT. The results show that
      OmpG-16S is responsive to pH change as indicated by the Amide I band shift upon a
      switch from acidic to neutral pH. This spectral shift is consistent with that
      observed in OmpG-WT, which confirms the existence of structural differences
      consistent with the presence of the open or closed state. Secondary structure
      analysis after curve-fitting of Amide I band revealed that the additional
      residues do not fold into beta-sheet; rather they are in the form of turns and
      unordered structure. In thermal stability experiments, OmpG-16S is found to be as
      stable as OmpG-WT. Additionally, H/D exchange experiments showed no difference in
      the exchange rate of OmpG-16S between the acidic and alkaline pH, suggesting that
      the loop L6 is no longer sufficient to block the pore entrance at acidic pH. 

PMID- 25958108
TI  - Dyadic validity of the Decisional Conflict Scale: common patient/physician
      measures of patient uncertainty were identified.
AB  - OBJECTIVES: We aimed to assess the dyadic validity of the Decisional Conflict
      Scale (DCS) for assessing shared decision making in clinical consultations. We
      applied dyadic criteria, which consider the patient and physician as an
      interactive dyad instead of as independent individuals, to identify common
      patient/physician measures of patient uncertainty. STUDY DESIGN AND SETTING:
      Patients and their physicians, participating in a randomized clustered trial,
      completed separately an adapted version of the DCS with five subscales. We
      performed factor analysis on the full DCS and each subscale independently. We
      defined a measure as dyadic when measurement invariance across patients and
      physicians was supported. RESULTS: We analyzed 332 paired responses (physicians
      with adults or with parents and children) at study entry and 339 at exit. Factor
      analysis showed that the full DCS is not a valid dyadic measure. However,
      independent analysis of each subscale showed measurement invariance for values
      clarity, support, and effective decision (comparative fit index range, 0.93-1;
      root mean square error of approximation range, 0-0.07; and P-value > 0.05).
      CONCLUSION: Application of our dyadic validation criterion indicated that the
      full DCS cannot be considered a dyadic measure. However, three of its subscales,
      values clarity, support and effective decision, are valid dyadic measures.

PMID- 25958107
TI  - Influenza virus-mediated membrane fusion: Structural insights from electron
      microscopy.
AB  - Influenza virus, the causative agent of flu, enters the host cell by endocytosis.
      The low pH encountered inside endosomes triggers conformational changes in the
      viral glycoprotein hemagglutinin (HA), that mediate fusion of the viral and
      cellular membranes. This releases the viral genome into the cytoplasm of the
      infected cell, establishing the onset of the replication cycle. To investigate
      the structural basis of HA-mediated membrane fusion, a number of techniques have
      been employed. These include X-ray crystallography, which has provided atomic
      models of the HA ectodomain in its initial (pre-fusion) state and of part of HA
      in its final (post-fusion) state. However, this left an information deficit
      concerning many other aspects of the fusion process. Electron microscopy (EM)
      approaches are helping to fill this void. For example, influenza virions at
      neutral pH have been imaged by cryo-EM and cryo-electron tomography (cryo-ET);
      thin section EM has shown that influenza viruses enter the cell by endocytosis;
      the large-scale structural changes in HA when virions are exposed to low pH (pre
      fusion to post-fusion states) have been visualized by negative staining and cryo
      EM; acidification also induces structural changes in the M1 matrix layer and its
      separation from the viral envelope; intermediate HA conformations between its pre
      and post-fusion states have been detected by cryo-ET supplemented with
      subtomogram averaging; and fusion of influenza virions with liposomes has been
      visualized by cryo-ET. In this review, we survey EM-based contributions towards
      the characterization of influenza virus-mediated membrane fusion and anticipate
      the potential for future developments. 

PMID- 25958110
TI  - Cancer incidence and all-cause mortality in a cohort of 21,582 Norwegian military
      peacekeepers deployed to Lebanon during 1978-1998.
AB  - OBJECTIVE: We investigated cancer incidence and all-cause mortality among 21,582
      Norwegian male military peacekeepers deployed to Lebanon during 1978-1998. We
      also looked at cancer risk according to duration of service in Lebanon, in the
      occupational groups of cooks and mechanics, and the risk of alcohol- and smoking
      related cancers among those who served during high- or low-conflict periods.
      METHODS: The cohort was followed for cancer incidence and all-cause mortality
      from 1978 through 2012. Standardised incidence ratios (SIR) for cancer and
      mortality ratios (SMR) were calculated from national rates for the total cohort.
      SIRs were calculated according to duration of service; among cooks and mechanics;
      and according to high- and low-conflict exposure. Poisson regression, expressed
      as rate ratio (RR), was used to see the effect of duration of service, and of
      conflict exposure. RESULTS: A decreased risk was found for cancer incidence
      overall (1050 cases, SIR=0.90, 95% confidence interval [CI] 0.84-0.95) and for
      cancers of the prostate (SIR=0.78) and skin (other than melanoma) (SIR=0.58). The
      incidence of rectal cancer was 73% higher in those who served for 1 year or more
      than in those with shorter-term service (RR=1.73, 95% CI 1.00-3.02). The cancer
      risk in cooks and mechanics was within expected values. The risk of lung cancer
      was higher in the high-conflict exposure group than in the low-conflict exposure
      group (RR=1.79; 95% CI 1.00-3.18). In the total cohort, all-cause mortality was
      lower than expected (SMR=0.83; 95% CI 0.78-0.88). CONCLUSION: We found a "healthy
      soldier effect" for overall cancer incidence and all-cause mortality. Service
      during high-conflict periods was associated with a higher risk of lung cancer
      than service during low-conflict periods, but this risk was in line with that of
      the reference population.

PMID- 25958109
TI  - Developing a smoke free homes initiative in Kerala, India.
AB  - BACKGROUND: Results of the Global Adult Tobacco Survey in Kerala, India found
      that 42 % of adults were exposed to second hand smoke (SHS) inside the home.
      Formative research carried out in rural Kerala suggests that exposure may be much
      higher. Numerous studies have called for research and intervention on SHS
      exposure among women and children as an important component of maternal and child
      health activities. METHODS: Community-based participatory research was carried
      out in Kerala. First, a survey was conducted to assess prevalence of SHS exposure
      in households. Next, a proof of concept study was conducted to develop and test
      the feasibility of a community-wide smoke free homes initiative. Educational
      materials were developed and pretested in focus groups. After feasibility was
      established, pilot studies were implemented in two other communities. Post
      intervention, surveys were conducted as a means of assessing changes in community
      support. RESULTS: At baseline, between 70 and 80 % of male smokers regularly
      smoked inside the home. Over 80 % of women had asked their husband not to do so.
      Most women felt powerless to change their husband's behavior. When women were
      asked about supporting a smoke free homes intervention, 88 % expressed support
      for the idea, but many expressed doubt that their husbands would comply.
      Educational meetings were held to discuss the harms of second hand smoke.
      Community leaders signed a declaration that their community was part of the smoke
      free homes initiative. Six months post intervention a survey was conducted in
      these communities; between 34 and 59 % of men who smoked no longer smoked in
      their home. CONCLUSIONS: The smoke free homes initiative is based on the
      principle of collective efficacy. Recognizing the difficulty for individual women
      to effect change in their household, the movement establishes a smoke free
      community mandate. Based on evaluation data from two pilot studies, we can
      project that between a 30 and 60 % reduction of smoking in the home may be
      achieved, the effect size determined by how well the smoke free home steps are
      implemented, the characteristics of the community, and the motivation of
      community level facilitators.

PMID- 25958111
TI  - Surgical treatment for fibrous dysplasia of femoral neck with mild but prolonged
      symptoms: a case series.
AB  - BACKGROUND: The proximal femur is one of the most common sites involved by
      fibrous dysplasia. In cases with mild deformity that does not require corrective
      surgery, occasional patients suffer sustained pain because of repeated
      microfractures. This study aimed to clarify the outcomes of surgery with
      autogenous fibular cortical strut grafting and compression hip screw fixation.
      METHODS: Since 2002, eight consecutive patients (nine hips) with femoral neck
      fibrous dysplasia without severe deformity were prospectively treated with
      autogenous fibular strut grafting and compression hip screw fixation. RESULTS:
      Mean age of patients was 35 years. Mean follow-up of patients after surgery was
      75 months. Most of the patients could walk with full weight-bearing 2 weeks after
      surgery. Functional score of lower extremity was significantly improved from 65 %
      to 95 % (P = 0.001). Femoral neck angle was increased from 127 to 130. Donor site
      of strut cortical fibula showed good regeneration with beta-tricalcium phosphate.
      CONCLUSIONS: Autogenous fibular cortical strut grafting and compression hip screw
      fixation achieved good post-operative function and provided an early return to
      work for adult patients with fibrous dysplasia of the femoral neck with mild but
      prolonged symptoms. Morbidity in the donor site of fibula strut is minimal with
      the use of beta-tricalcium phosphate.

PMID- 25958112
TI  - In vivo antiplasmodial and toxicological effect of crude ethanol extract of
      Echinops kebericho traditionally used in treatment of malaria in Ethiopia.
AB  - BACKGROUND: Medicinal plants have contributed significantly to current malaria
      treatment. Emergence of resistance to currently available drugs has necessitated
      the search for new plant-based anti-malarial agents and several plant-based,
      pharmacologically active anti-malarial compounds have been isolated. This study
      was conducted to validate the traditional usage of Echinops kebericho for
      treating malaria in the traditional health care system of Ethiopia. METHODS: The
      roots of E. kebericho were collected from Masha Woreda, Sheka Zone. After
      collection, the plant materials were identified by a taxonomist, dried under
      shade and crushed to powder for extraction. The powdered roots were extracted by
      maceration using 70 % ethanol. Acute toxicity study of the crude extract was
      carried out in Swiss albino mice. The in vivo anti-malarial activity of plant
      extract (200, 350 and 500 mg/kg) of E. kebericho roots against a chloroquine (CQ)
      sensitive strain of Plasmodium berghei strain ANKA was assessed using the four
      day suppressive test procedure. Parameters such as parasitaemia, packed cell
      volume, body weight and survival time were then determined using standard tests.
      RESULTS: Oral administration of the ethanol extract showed significant (P<0.001)
      parasitaemia suppression at dose levels of 350 and 500 mg/kg in dose-related
      manner compared with the negative control. Five hundred mg/kg showed the highest
      (57.29+/-1.76 %) parasitaemia suppression. The survival times of P. berghei
      infected mice were also increased in a dose-dependent manner but the test
      material did not prevent weight loss associated with increased parasitaemia. The
      result also showed the plant material prevented the loss in packed cell volume
      associated with increased parasitaemia. Its oral LD50 was found to be greater
      than 5,000 mg/kg, indicating its wider safety margin in mice. CONCLUSION: The
      result revealed the ethanol extract of E. kebericho roots has anti-malarial
      activity against P. berghei in an animal model and lends support to the use of
      the plant to combat malaria in Ethiopian folk medicine. Further work is necessary
      to isolate, identify and characterize the active principles from the plant
      material.

PMID- 25958113
TI  - Reply: To PMID 25465933.

PMID- 25958114
TI  - Diagnostic yield of routine noninvasive cardiovascular testing in low-risk acute
      chest pain patients.
AB  - Contemporary professional society recommendations for patients presenting to the
      emergency department with acute chest pain and low clinical risk encourage
      noninvasive testing for coronary artery disease (CAD) before, or shortly after,
      discharge from the emergency department. Recent reports indicate that a strategy
      of universal testing has a low diagnostic yield and may not be necessary. We
      examined data from a prospective cohort of patients who underwent evaluation of
      acute chest pain in our chest pain evaluation center (CPEC). Patients presenting
      with normal initial electrocardiogram and cardiac injury markers were eligible
      for observation and noninvasive testing for CAD in our CPEC. All patients were
      asked to participate in the prospective registry. The 213 subjects who consented
      were young, obese, and predominantly women (mean age 43.8 +/- 12.5, mean body
      mass index of 30.8 +/- 7, 64.8% women). Prevalence of diabetes was 10.3%
      (hypertension 37.1%, hyperlipidemia 17.8%, and current tobacco use 23.5%)
      Exercise treadmill testing was the primary method of evaluation (n = 104, 49%)
      followed by computed tomography coronary angiography (n = 58, 27%) and myocardial
      perfusion imaging (n = 20, 9%). Of 203 patients who underwent testing, 11 had
      abnormal test results, 4 of whom had obstructive CAD based on invasive coronary
      angiography. The positive predictive value for obstructive CAD after an abnormal
      test was 45.5%, and the overall diagnostic yield for obstructive CAD was 2.5%. In
      conclusion, in patients with acute chest pain evaluated in a CPEC, the yield of
      routine use of noninvasive testing for CAD was minimal and the positive
      predictive value of an abnormal test was low. 

PMID- 25958115
TI  - Preventive methylene blue treatment preserves cognition in mice expressing full
      length pro-aggregant human Tau.
AB  - INTRODUCTION: Neurofibrillary tangles (NFT) composed of Tau are hallmarks of
      neurodegeneration in Alzheimer disease. Transgenic mice expressing full-length
      pro-aggregant human Tau (2N4R Tau-DeltaK280, termed Tau(DeltaK)) or its repeat
      domain (TauRD-DeltaK280, TauRD(DeltaK)) develop a progressive Tau pathology with
      missorting, phosphorylation, aggregation of Tau, loss of synapses and functional
      deficits. Whereas TauRD(DeltaK) assembles into NFT concomitant with neuronal
      death, Tau(DeltaK) accumulates into Tau pretangles without overt neuronal loss.
      Both forms cause a comparable cognitive decline (with onset at 10mo and 12mo,
      respectively), which is rescued upon switch-off of transgene expression. Since
      methylene blue (MB) is able to inhibit Tau aggregation in vitro, we investigated
      whether MB can prevent or rescue Tau-induced cognitive impairments in our mouse
      models. Both types of mice received MB orally using different preventive and
      therapeutic treatment protocols, initiated either before or after disease onset.
      The cognitive status of the mice was assessed by behavior tasks (open field,
      Morris water maze) to determine the most successful conditions for therapeutic
      intervention. RESULTS: Preventive and therapeutic MB application failed to avert
      or recover learning and memory deficits of TauRD(DeltaK) mice. Similarly,
      therapeutic MB treatment initiated after onset of cognitive impairments was
      ineffective in Tau(DeltaK) mice. In contrast, preventive MB application starting
      before onset of functional deficits preserved cognition of Tau(DeltaK) mice.
      Beside improved learning and memory, MB-treated Tau(DeltaK) mice showed a strong
      decrease of insoluble Tau, a reduction of conformationally changed (MC1) and
      phosphorylated Tau species (AT180, PHF1) as well as an upregulation of protein
      degradation systems (autophagy and proteasome). This argues for additional
      pleiotropic effects of MB beyond its properties as Tau aggregation inhibitor.
      CONCLUSIONS: Our data support the use of Tau aggregation inhibitors as potential
      drugs for the treatment of AD and other tauopathies and highlights the need for
      preventive treatment before onset of cognitive impairments.

PMID- 25958117
TI  - Increasing portion sizes of fruits and vegetables in an elementary school lunch
      program can increase fruit and vegetable consumption.
AB  - Increasing portion size can increase children's consumption of food. The goal of
      this study was to determine whether increasing the portion sizes of fruits and
      vegetables in an elementary school cafeteria environment would increase
      children's consumption of them. We measured each child's consumption of the fruit
      and vegetables served in a cafeteria line on a control day (normal cafeteria
      procedures) and on two intervention days. When we increased the portion size of 3
      of the 4 fruits and vegetables by about 50%, children who took those foods
      increased their consumption of them. Although this was an effective strategy for
      increasing fruit and vegetable consumption among students who took those foods,
      many children chose not to take any fruits or vegetables. Further efforts are
      needed to increase children's selection and consumption of fruits and vegetables
      in an environment of competing foods of higher palatability. 

PMID- 25958116
TI  - Menu label accuracy at a university's foodservices. An exploratory recipe
      nutrition analysis.
AB  - The increase in the weight of American adults and children has been positively
      associated with the prevalence of the consumption of food-away-from-home. The
      objective was to assess the accuracy of claimed nutritional information of foods
      purchased in contracted foodservices located on the campus of an institution of
      higher education. Fifty popular food items were randomly collected from five main
      dining outlets located on a selected campus in the northeastern United States.
      The sampling was repeated three times on separate occasions for an aggregate
      total of 150 food samples. The samples were then weighed and assessed for
      nutrient composition (protein, cholesterol, fiber, carbohydrates, total fat,
      calories, sugar, and sodium) using nutrient analysis software. Results were
      compared with foodservices' published nutrition information. Two group
      comparisons, claimed and measured, were performed using the paired-sample t-test.
      Descriptive statistics were used as well. Among the nine nutritional values, six
      nutrients (total fat, sodium, protein, fiber, cholesterol, and weight) had more
      than 10% positive average discrepancies between measured and claimed values.
      Statistical significance of the variance was obtained in four of the eight
      categories of nutrient content: total fat, sodium, protein, and cholesterol (P <
      .05). Significance was also reached in the variance of actual portion weight
      compared to the published claims (P < .001). Significant differences of portion
      size (weight), total fat, sodium, protein, and cholesterol were found among the
      sampled values and the foodservices' published claims. The findings from this
      study raise the concern that if the actual nutritional information does not
      accurately reflect the declared values on menus, conclusions, decisions and
      actions based on posted information may not be valid.

PMID- 25958118
TI  - Experiences with the use of complementary and alternative medicine in nursing
      homes: A focus group study.
AB  - INTRODUCTION: The use of complementary and alternative medicine is increasing
      outside the Norwegian public health service. The purpose of this study was to
      gain insight into the experiences of nurses and auxiliary nurses with the use of
      CAM in care for nursing home residents. METHOD: Focus group interviews with a
      total of thirteen nurses and auxiliary nurses from three nursing homes were
      conducted. Data were analyzed using systematic text condensation. RESULTS:
      Participants had experiences from aromatherapy, plant medicine, music therapy and
      pet therapy. They experienced the use of CAM as effective, exciting and
      rewarding, but also challenging and dependent on supportive leaders. CAM
      supported person-centered and holistic care. The participants lacked competence
      and knowledge. CONCLUSION: Nurses and auxiliary nurses were enthusiastic about
      using CAM in their care for nursing home residents, but they lacked knowledge
      about it. The status of CAM in nursing education programs must be examined.

PMID- 25958119
TI  - Thoracic aorta to femoral artery bypass allows secondary kidney transplantation
      in case of major iliac artery disease.
AB  - Iliac artery major calcifications can compromise kidney graft. First-performed
      prosthetic arterial bypass from the thoracic aorta to the femoral artery allows
      secondary kidney transplantation. Four patients were submitted to this procedure.
      No patient died during the postoperative period or the follow-up. The median time
      to receive a kidney graft after the arterial surgery was 24 months (4-52). The
      normalization of the sera creatinine level was 6.4 days (2-15). The median follow
      up was 38 months (7-79). In our experience, using lateral side clamping of the
      descendant thoracic aorta during the proximal implantation of the arterial graft
      avoids bleeding and visceral abdominal ischemia. The secondary performed kidney
      graft is safe on a very available arterial conduit.

PMID- 25958120
TI  - Axillofemoral bypass for kidney transplant protection during open repair of
      abdominal aortic aneurysm.
AB  - The need to treat an abdominal aortic aneurysm (AAA) in kidney transplanted
      patient is a rare event. To date, no method to protect the kidney during the
      aneurysm treatment has been identified as undeniably relevant. On the other hand,
      the advantage of endovascular treatment of the aneurysm (EVAR) is to avoid
      transplanted kidney injury. Unfortunately, EVAR is not always available leading
      to open repair and then aortic cross clamping. We report here 3 cases of AAA open
      repair in kidney transplanted patients using a temporary axillofemoral bypass to
      protect the renal function. 

PMID- 25958121
TI  - Relief of delayed oxidative stress by ascorbic acid can suppress radiation
      induced cellular senescence in mammalian fibroblast cells.
AB  - Ionizing radiation-induced cellular senescence is thought to be caused by nuclear
      DNA damage that cannot be repaired. However, here we found that radiation induces
      delayed increase of intracellular oxidative stress after irradiation. We
      investigated whether the relief of delayed oxidative stress by ascorbic acid
      would suppress the radiation-induced cellular senescence in Syrian golden hamster
      embryo (SHE) cells. We observed that the level of oxidative stress was
      drastically increased soon after irradiation, then declined to the level in non
      irradiated cells, and increased again with a peak on day 3 after irradiation. We
      found that the inductions of cellular senescence after X-irradiation were reduced
      along with suppression of the delayed induction of oxidative stress by treatment
      with ascorbic acid, but not when oxidative stress occurred immediately after
      irradiation. Moreover, treatment of ascorbic acid inhibited p53 accumulation at 3
      days after irradiation. Our data suggested a delayed increase of intracellular
      oxidative stress levels plays an important role in the process of radiation
      induced cellular senescence by p53 accumulation.

PMID- 25958122
TI  - Renal tubular damage may contribute more to acute hyperglycemia induced kidney
      injury in non-diabetic conscious rats.
AB  - AIMS: Growing evidences suggest that acute hyperglycemia is strongly related to
      kidney injury. Our study aimed to investigate the effects of acute hyperglycemia
      on kidney glomerular and tubular impairment in non-diabetic conscious rats.
      METHODS: Non-diabetic conscious rats were randomly subjected to 6h of saline
      (control group) or high glucose (acute hyperglycemia group) infusion. Blood
      glucose was maintained at 16.0-18.0 mmol/L in acute hyperglycemia group. Renal
      structure and function alterations, systemic/renal inflammation and oxidative
      stress markers were assessed, and apoptosis markers of renal inherent cells were
      evaluated. RESULTS: Acute hyperglycemia caused significant injury to structure of
      glomerular filtration barrier, tubular epithelial cells and peritubular vascular
      endothelial cells. It increased urinary microalbumin (68.01 +/- 27.09 MUg/24h vs
      33.81 +/- 13.81 MUg/24h , P=0.014), beta2-microglobulin, Cystatin C, urinary and
      serous neutrophil gelatinase-associated lipocalin levels (P < 0.05). Acute
      hyperglycemia decreased megalin and cubilin expression, activated systemic and
      renal oxidative stress as well as inflammation and promoted renal inherent cell
      apoptosis. CONCLUSIONS: Acute hyperglycemia causes significant injury to kidney
      function and structure. Compared with damages of glomerular filtration barrier,
      renal tubular injury may contribute more to acute hyperglycemia induced
      proteinuria. Activation of inflammation especially renal inflammation, oxidative
      stress and enhanced apoptosis may be the underlying mechanisms.

PMID- 25958123
TI  - [Portal hypertension and cholestatic jaundice as a form of presentation of
      systemic amyloidosis].

PMID- 25958124
TI  - A novel fluid-feeding mechanism for microbivory in the Acariformes (Arachnida:
      Acari).
AB  - Low temperature scanning electron microscopy (LT-SEM) has revealed anatomical
      details suggesting that Osperalycus and Gordialycus (Acariformes: Nematalycidae)
      have an unusual feeding apparatus that is hypothesized to be specialized for
      feeding on the fluid contents of small microorganisms (diameter<5 MUm). Both mite
      genera have a feeding strategy that appears to involve picking up small
      microorganisms and placing them onto the subcapitulum for puncturing. However,
      they have slightly different variants of the same basic rupturing mechanism.
      Whereas Gordialycus has evolved expansive and convergent rutella to hold the
      microorganisms in place while pushing chelicerae into them, Osperalycus has
      evolved a pouch into which a microorganism is inserted. The rutella reinforce
      this pouch while the chelicerae break up the microorganism. Both types of
      mouthpart apparatus seem to be adapted to minimize waste, an appropriate
      specialization given the organically impoverished habitats in which these mites
      live.

PMID- 25958125
TI  - Is HbA1c a valid surrogate for macrovascular and microvascular complications in
      type 2 diabetes?
AB  - Recent recommendations regarding type 2 diabetes (T2D) patients' treatments have
      focused on personalizing glycosylated haemoglobin (HbA1c) targets. Because the
      relationship between HbA1c and diabetes prognosis has been established from large
      prospective cohorts, it is valid to question the extrapolation from population
      based risk reduction estimations to individual predictions. Our study aimed to
      investigate the relationship between HbA1c reductions and clinical outcomes in
      randomized controlled trials (RCTs), using a meta-regression approach. Included
      were RCTs comparing intensive vs. standard glucose-lowering regimens for
      cardiovascular events and microvascular complications in T2D patients. Eight
      studies (33,396 patients) providing data for HbA1c reductions were found. In our
      meta-regression, HbA1c decreases were not significantly associated with
      reductions in our main study outcomes: total and cardiovascular mortality. They
      were also not associated with any of the secondary endpoints, including
      myocardial infarction, stroke and severe hypoglycaemia. Sensitivity analysis
      showed a significant correlation only between HbA1c-lowering and severe
      hypoglycaemia (P = 0.014). Meta-regression analysis could find no significant
      association between HbA1c-lowering and a decrease in clinical outcomes, thereby
      questioning the use of HbA1c as a surrogate outcome for T2D-related
      complications. Thus, RCTs vs. placebo are urgently required to evaluate the risk
      benefit ratios of therapeutic strategies beyond HbA1c control in T2D patients.

PMID- 25958126
TI  - Simultaneous determination of binary mixture of amlodipine besylate and atenolol
      based on dual wavelengths.
AB  - Four, accurate, precise, and sensitive spectrophotometric methods are developed
      for simultaneous determination of a binary mixture of amlodipine besylate (AM)
      and atenolol (AT). AM is determined at its lambdamax 360 nm ((0)D), while
      atenolol can be determined by four different methods. Method (A) is absorption
      factor (AF). Method (B) is the new ratio difference method (RD) which measures
      the difference in amplitudes between 210 and 226 nm. Method (C) is novel constant
      center spectrophotometric method (CC). Method (D) is mean centering of the ratio
      spectra (MCR) at 284 nm. The methods are tested by analyzing synthetic mixtures
      of the cited drugs and they are applied to their commercial pharmaceutical
      preparation. The validity of results is assessed by applying standard addition
      technique. The results obtained are found to agree statistically with those
      obtained by official methods, showing no significant difference with respect to
      accuracy and precision.

PMID- 25958127
TI  - Housing interventions and health: Quantifying the impact of indoor particles on
      mortality and morbidity with disease recovery.
AB  - Housing interventions for energy efficiency and greenhouse gas emission reduction
      have the potential to reduce exposure to indoor air pollution if they are
      implemented correctly. This work assessed the health impacts of home energy
      efficiency measures in England and Wales resulting in a reduction in average
      indoor PM2.5 exposures of 3 MUg m(-3). The assessment was performed using a new
      multistate life table model which allows transition into and between multiple
      morbid states, including recovery to disease-free status and relapse, with
      transition rates informed by age- and cause-specific disease prevalence,
      incidence and mortality data. Such models have not previously included disease
      recovery. The results demonstrate that incorporation of recovery in the model is
      necessary for conditions such as asthma which have high incidence in early life
      but likelihood of recovery in adulthood. The impact assessment of the home energy
      efficiency intervention showed that the reduction in PM2.5 exposure would be
      associated with substantial benefits for mortality and morbidity from asthma,
      coronary heart disease and lung cancer. The overall impact would be an increase
      in life expectancy of two to three months and approximately 13 million QALYs
      gained over the 90 year follow-up period. Substantial quality-of-life benefits
      were also observed, with a decrease in asthma over all age groups and larger
      benefits due to reduced coronary heart disease and lung cancer, particularly in
      older age groups. The multistate model with recovery provides important
      additional information for assessing the impact on health of environmental
      policies and interventions compared with mortality-only life tables, allowing
      more realistic representation of diseases with substantial non-mortality burdens.

PMID- 25958129
TI  - New technologies and innovations in hysteroscopy.
AB  - Ambulatory services, with the performance of diagnostic and operative
      hysteroscopy as an outpatient or office procedure, are providing much of the
      stimulus for the development of devices that will offer women a better
      hysteroscopy experience. For the many women who are readily able to tolerate
      outpatient hysteroscopy, it offers significant advantages, as they can receive
      safe, efficient and effective assessment and treatment of abnormal uterine
      bleeding, with avoidance of the disadvantages of general anaesthesia and hospital
      admission. In addition, provision of such services is cost effective. Whilst the
      focus for the development of new devices has been the improvement of ambulatory
      hysteroscopy services, new instrumentation may be beneficial for hysteroscopy
      procedures in any setting. For ambulatory services, important goals are to reduce
      pain and the duration of procedures, and to enable the ready delivery of both
      diagnostic and therapeutic outpatient hysteroscopy. This article discusses
      innovations for both diagnosis and treatment. Much of the information available
      about these new devices has been obtained from the manufacturers or from
      published abstracts submitted for presentation at international meetings that
      have not been peer-reviewed. Some of the reported studies have been randomised
      controlled trials, others the results of early investigations. 

PMID- 25958128
TI  - Effectiveness of chronic care models: opportunities for improving healthcare
      practice and health outcomes: a systematic review.
AB  - BACKGROUND: The increasing prevalence of chronic disease and even multiple
      chronic diseases faced by both developed and developing countries is of
      considerable concern. Many of the interventions to address this within primary
      healthcare settings are based on a chronic care model first developed by MacColl
      Institute for Healthcare Innovation at Group Health Cooperative. METHODS: This
      systematic literature review aimed to identify and synthesise international
      evidence on the effectiveness of elements that have been included in a chronic
      care model for improving healthcare practices and health outcomes within primary
      healthcare settings. The review broadens the work of other similar reviews by
      focusing on effectiveness of healthcare practice as well as health outcomes
      associated with implementing a chronic care model. In addition, relevant case
      series and case studies were also included. RESULTS: Of the 77 papers which met
      the inclusion criteria, all but two reported improvements to healthcare practice
      or health outcomes for people living with chronic disease. While the most
      commonly used elements of a chronic care model were self-management support and
      delivery system design, there were considerable variations between studies
      regarding what combination of elements were included as well as the way in which
      chronic care model elements were implemented. This meant that it was impossible
      to clearly identify any optimal combination of chronic care model elements that
      led to the reported improvements. CONCLUSIONS: While the main argument for
      excluding papers reporting case studies and case series in systematic literature
      reviews is that they are not of sufficient quality or generalizability, we found
      that they provided a more detailed account of how various chronic care models
      were developed and implemented. In particular, these papers suggested that
      several factors including supporting reflective healthcare practice, sending
      clear messages about the importance of chronic disease care and ensuring that
      leaders support the implementation and sustainability of interventions may have
      been just as important as a chronic care model's elements in contributing to the
      improvements in healthcare practice or health outcomes for people living with
      chronic disease.

PMID- 25958130
TI  - A novel flow cytometry-based tool for determining the efficiency of human
      cytomegalovirus infection in THP-1 derived macrophages.
AB  - Human cytomegalovirus (hCMV) is a ubiquitous pathogen that causes congenital
      infection and severe infections in immunocompromised patients. Chronic hCMV
      infection may also play an important role in immunosenescence and adverse health
      outcomes in older adults. THP-1, a human monocytic cell line and its derived
      macrophages serve as a useful cell culture model for mechanistic studies of hCMV
      infection and its underlying biology. A major methodological challenge is the
      lack of a quick and reliable tool to accurately determine the efficiency of hCMV
      infection in THP-1 derived macrophages. In this study, we developed a flow
      cytometry based method using commercially available monoclonal antibody (MAb)
      against hCMV immediate early (IE) antigen that can accurately determine infection
      efficiency. We used 0.5% formaldehyde for fixation, 90% methanol for
      permeabilization, and incubation with FITC conjugated MAb at 37 degrees C. The
      method was tested by hCMV infection with laboratory Towne strain in the presence
      or absence of hydrocortisone. It was also compared with the routine flow
      cytometry protocol using Cytofix/Cytoperm solution and with immunofluorescence.
      The results indicate that this new method is reliable and time saving for
      accurate determination of infection efficiency. It may facilitate further
      investigations into the underlying biological mechanisms of hCMV infection. 

PMID- 25958131
TI  - Using proximity biotinylation to detect herpesvirus entry glycoprotein
      interactions: Limitations for integral membrane glycoproteins.
AB  - Herpesvirus entry into cells requires coordinated interactions among several
      viral transmembrane glycoproteins. Viral glycoproteins bind to receptors and
      interact with other glycoproteins to trigger virus-cell membrane fusion. Details
      of these glycoprotein interactions are not well understood because they are
      likely transient and/or low affinity. Proximity biotinylation is a promising
      protein-protein interaction assay that can capture transient interactions in live
      cells. One protein is linked to a biotin ligase and a second protein is linked to
      a short specific acceptor peptide (AP). If the two proteins interact, the ligase
      will biotinylate the AP, without requiring a sustained interaction. To examine
      herpesvirus glycoprotein interactions, the ligase and AP were linked to herpes
      simplex virus 1 (HSV1) gD and Epstein Barr virus (EBV) gB. Interactions between
      monomers of these oligomeric proteins (homotypic interactions) served as positive
      controls to demonstrate assay sensitivity. Heterotypic combinations served as
      negative controls to determine assay specificity, since HSV1 gD and EBV gB do not
      interact functionally. Positive controls showed strong biotinylation, indicating
      that viral glycoprotein proximity can be detected. Unexpectedly, the negative
      controls also showed biotinylation. These results demonstrate the special
      circumstances that must be considered when examining interactions among
      glycosylated proteins that are constrained within a membrane. 

PMID- 25958132
TI  - Next generation sequencing in endocrine practice.
AB  - With the completion of the Human Genome Project and advances in genomic
      sequencing technologies, the use of clinical molecular diagnostics has grown
      tremendously over the last decade. Next-generation sequencing (NGS) has overcome
      many of the practical roadblocks that had slowed the adoption of molecular
      testing for routine clinical diagnosis. In endocrinology, targeted NGS now
      complements biochemical testing and imaging studies. The goal of this review is
      to provide clinicians with a guide to the application of NGS to genetic testing
      for endocrine conditions, by compiling a list of established gene mutations
      detectable by NGS, and highlighting key phenotypic features of these disorders.
      As we outline in this review, the clinical utility of NGS-based molecular testing
      for endocrine disorders is very high. Identifying an exact genetic etiology
      improves understanding of the disease, provides clear explanation to families
      about the cause, and guides decisions about screening, prevention and/or
      treatment. To illustrate this approach, a case of hypophosphatasia with a
      pathogenic mutation in the ALPL gene detected by NGS is presented. 

PMID- 25958133
TI  - Process optimization and kinetics of biodiesel production from neem oil using
      copper doped zinc oxide heterogeneous nanocatalyst.
AB  - Heterogeneous nanocatalyst has become the choice of researchers for better
      transesterification of vegetable oils to biodiesel. In the present study,
      transesterification reaction was optimized and kinetics was studied for biodiesel
      production from neem oil using CZO nanocatalyst. The highly porous and non
      uniform surface of the CZO nanocatalyst was confirmed by AFM analysis, which
      leads to the aggregation of CZO nanoparticles in the form of multi layered
      nanostructures. The 97.18% biodiesel yield was obtained in 60min reaction time at
      55 degrees C using 10% (w/w) CZO nanocatalyst and 1:10 (v:v) oil:methanol ratio.
      Biodiesel yield of 73.95% was obtained using recycled nanocatalyst in sixth
      cycle. The obtained biodiesel was confirmed using GC-MS and (1)H NMR analysis.
      Reaction kinetic models were tested on biodiesel production, first order kinetic
      model was found fit with experimental data (R(2)=0.9452). The activation energy
      of 233.88kJ/mol was required for transesterification of neem oil into biodiesel
      using CZO nanocatalyst. 

PMID- 25958134
TI  - Bioabatement with hemicellulase supplementation to reduce enzymatic hydrolysis
      inhibitors.
AB  - A stepwise removal of inhibitory compounds by bioabatement combined with
      hemicellulase supplementation was conducted to enhance cellulose hydrolysis of
      liquid hot water-pretreated corn stover. Results showed that the fungus
      Coniochaeta ligniaria NRRL30616 eliminated most of the enzyme and fermentation
      inhibitors from liquid hot water-pretreated corn stover hydrolysates. Moreover,
      addition of hemicellulases after bioabatement and before enzymatic hydrolysis of
      cellulose achieved 20% higher glucose yields compared to non-treated samples.
      This work presents the mechanisms by which supplementation of the fungus with
      hemicellulase enzymes enables maximal conversion, and confirms the inhibitory
      effect of xylo-oligosaccharides in corn stover hydrolysates once the dominant
      inhibitory effect of phenolic compounds is removed. 

PMID- 25958136
TI  - Reassortant human group C rotaviruses in Hungary.

PMID- 25958135
TI  - Novel Nsp2 deletion based on molecular epidemiology and evolution of porcine
      reproductive and respiratory syndrome virus in Shandong Province from 2013 to
      2014.
AB  - Porcine reproductive and respiratory syndrome (PRRS) is an economically important
      swine disease affecting swine worldwide. In this study, a total of 385 samples
      were collected from Shandong pig farms during 2013 and 2014, when pigs were not
      inoculated with any vaccine. Results indicated that, out of 385 samples, 47
      (12.21%) were PRRSV-RNA-positive. The gene sequence analysis of 12 ORF5, 12 ORF7,
      and 8 Nsp2 of these samples was used to determine the molecular epidemiology of
      PRRSV in different parts of China's Shandong Province. The phylogenetic tree
      based on these 3 genes indicated that the Chinese PRRSV strains could be divided
      into five subgroups and two large groups. The 8 study strains were clustered into
      subgroup IV, another 4 strains into subgroup I. The first 8 strains shared
      considerable homology with VR-2332 in ORF5 (96-97.5%), the other 4 strains shared
      considerable homology with JXA1 (94-98%). Phylogenetic tree of GP5 showed that
      the eight isolates formed a tightly novel clustered branch, subgroup V, which
      resembled but differed from isolate VR-2332. When examined using Nsp2 alone, the
      first 8 strains showed considerable homology with a U.S. vaccine strain, Ingelvac
      MLV (89.6-98.4%). One novel pattern of deletion was observed in Nsp2. The genetic
      diversity of genotype 2 PRRSV tended to vary in the field. The emergence of novel
      variants will probably be the next significant branch of PRRSV study. 

PMID- 25958137
TI  - Experimental removal of sexual selection leads to decreased investment in an
      immune component in female Tribolium castaneum.
AB  - Because of divergent selection acting on males and females arising from different
      life-history strategies, polyandry can be expected to promote sexual dimorphism
      of investment into immune function. In previous work we have established the
      existence of such divergence within populations where males and females are
      exposed to varying degrees of polyandry. We here test whether the removal of
      sexual selection via enforced monogamy generates males and females that have
      similar levels of investment in immune function. To test this prediction
      experimentally, we measured differences between the sexes in a key immune
      measurement (phenoloxidase (PO) activity) and resistance to the microsporidian
      Paranosema whitei in Tribolium castaneum lines that evolved under monogamous
      (sexual selection absent) vs polyandrous (sexual selection present) mating
      systems. At generation 49, all selected lines were simultaneously assessed for PO
      activity and resistance to their natural parasite P. whitei after two generations
      of relaxed selection. We found that the polyandrous regime was associated with a
      clear dimorphism in immune function: females had significantly higher PO
      activities than males in these lines. In contrast, there was no such difference
      between the sexes in the lines evolving under the monogamous regime. Survival in
      the infection experiment did not differ between mating systems or sexes. Removing
      sexual selection via enforced monogamy thus seems to erase intersexual
      differences in immunity investment. We suggest that higher PO activities in
      females that have evolved under sexual selection might be driven by the increased
      risk of infections and/or injuries associated with exposure to multiple males. 

PMID- 25958138
TI  - Determination of fifteen coccidiostats in feed at carry-over levels using liquid
      chromatography-mass spectrometry.
AB  - A multi-residue method has been developed and validated for the simultaneous
      determination of authorized (decoquinate, diclazuril, halofuginone, lasalocid,
      maduramicin, monensin, narasin, nicarbazin, robenidine, salinomycin and
      semduramicin) and non-authorized (amprolium, clopidol, ethopabate and
      toltrazuril) coccidiostats in animal feed. Feed samples were extracted with basic
      followed by acidified solution in methanol and, after centrifugation, were
      injected directly into LC-MS/MS system. Detection was performed in selected
      reaction monitoring mode with both positive and negative electrospray ionization.
      The time efficient validation experiment has verified the robustness of a method
      in different types of feed and on two separate LC-MS/MS instruments. The
      comparison of different quantification methods demonstrated that, against
      expectations, the standard addition did not prove better in comparison with
      matrix-matched calibration curve. Although the sample preparation was very easy,
      the observed matrix effects were not significant for the most part but they could
      explain the problems with the quantification of some coccidiostats. 

PMID- 25958139
TI  - Development and beyond: Strategy for long-term maintenance of an online laser
      diffraction particle size method in a spray drying manufacturing process.
AB  - The purpose of this manuscript is to present the intended use and long-term
      maintenance strategy of an online laser diffraction particle size method used for
      process control in a spray drying process. A Malvern Insitec was used for online
      particle size measurements and a Malvern Mastersizer was used for offline
      particle size measurements. The two methods were developed in parallel with the
      Mastersizer serving as the reference method. Despite extensive method development
      across a range of particle sizes, the two instruments demonstrated different
      sensitivities to material and process changes over the product lifecycle. This
      paper will describe the procedure used to ensure consistent alignment of the two
      methods, thus allowing for continued use of online real-time laser diffraction as
      a surrogate for the offline system over the product lifecycle. 

PMID- 25958140
TI  - Enhancement of xylose utilization from corn stover by a recombinant Escherichia
      coli strain for ethanol production.
AB  - Effects of substrate-selective inoculum prepared by growing on glucose, xylose,
      arabinose, GXA (glucose, xylose, arabinose, 1:1:1) and corn stover hydrolyzate
      (dilute acid pretreated and enzymatically hydrolyzed, CSH) on ethanol production
      from CSH by a mixed sugar utilizing recombinant Escherichia coli (strain FBR5)
      were investigated. The initial ethanol productivity was faster for the seed grown
      on xylose followed by GXA, CSH, glucose and arabinose. Arabinose grown seed took
      the longest time to complete the fermentation. Delayed saccharifying enzyme
      addition in simultaneous saccharification and fermentation of dilute acid
      pretreated CS by the recombinant E. coli strain FBR5 allowed the fermentation to
      finish in a shorter time than adding the enzyme simultaneously with xylose grown
      inoculum. Use of substrate selective inoculum and fermenting pentose sugars first
      under glucose limited condition helped to alleviate the catabolite repression of
      the recombinant bacterium on ethanol production from lignocellulosic hydrolyzate.

PMID- 25958141
TI  - Aeration and mass transfer optimization in a rectangular airlift loop
      photobioreactor for the production of microalgae.
AB  - Effects of superficial gas velocity and top clearance on gas holdup, liquid
      circulation velocity, mixing time, and mass transfer coefficient are investigated
      in a new airlift loop photobioreactor (PBR), and empirical models for its
      rational control and scale-up are proposed. In addition, the impact of top
      clearance on hydrodynamics, especially on the gas holdup in the internal airlift
      loop reactor, is clarified; a novel volume expansion technique is developed to
      determine the low gas holdup in the PBR. Moreover, a model strain of Chlorella
      vulgaris is cultivated in the PBR and the volumetric power is analyzed with a
      classic model, and then the aeration is optimized. It shows that the designed
      PBR, a cost-effective reactor, is promising for the mass cultivation of
      microalgae. 

PMID- 25958142
TI  - Biomass and pigments production in photosynthetic bacteria wastewater treatment:
      Effects of photoperiod.
AB  - This study aimed at enhancing the bacterial biomass and pigments production in
      together with pollution removal in photosynthetic bacteria (PSB) wastewater
      treatment via using different photoperiods. Different light/dark cycles and
      light/dark cycle frequencies were examined. Results showed that PSB had the
      highest biomass production, COD removal and biomass yield, and light energy
      efficiency with light/dark cycle of 2h/1h. The corresponding biomass, COD removal
      and biomass yield reached 2068mg/L, 90.3%, and 0.38mg-biomass/mg-COD-removal,
      respectively. PSB showed higher biomass production and biomass yield with higher
      light/dark cycle frequency. Mechanism analysis showed within a light/dark cycle
      from 1h/2h to 2h/1h, the carotenoid and bacteriochlorophyll production increased
      with an increase in light/dark cycle. Moreover, the pigment contents were much
      higher with lower frequency of 2-4 times/d. 

PMID- 25958143
TI  - Semi-continuous anaerobic digestion of different silage crops: VFAs formation,
      methane yield from fiber and non-fiber components and digestate composition.
AB  - This study presents the results of long-term semi-continuous experiments on
      anaerobic digestion at an HRT of 45d with ten silages: 2 annual and 4 perennial
      crops, and 4 mixtures of annual with perennial crops. The composition of
      substrates and digestates was determined with Van Soest's fractionation method.
      Removal of non-fiber materials ranged from 49.4% (Miscanthus sacchariflorus) to
      89.3% (Zea mays alone and mixed with M. sacchariflorus), that of fiber materials
      like lignin ranged from 0.005% (Z. mays alone and mixed with grasses at VS ratio
      of 90:10%) to 46.5% (Sida hermaphrodita). The lowest stability of anaerobic
      digestion, as confirmed by normalized data concentrations of volatile fatty
      acids, was reported for both miscanthuses and sugar sorghum. The methane yield
      coefficients for non-fiber and fiber materials were 0.3666 and 0.2556L/g,
      respectively. All digestate residues had high fertilizing value, especially those
      from mixtures of crops. 

PMID- 25958144
TI  - Pyrolysis mechanism study of minimally damaged hemicellulose polymers isolated
      from agricultural waste straw samples.
AB  - The pyrolysis mechanism of hemicellulose has been investigated using two
      minimally damaged hemicellulose polymers isolated from two agricultural straw
      samples. The obtained hemicelluloses have been characterized by multiple methods,
      and the results showed that they were mainly composed of l-arabino-4-O-methyl-d
      glucurono-d-xylan. Their O-acetyl groups and high degrees of polymerization and
      branching were well preserved. Their pyrolyses were subsequently investigated by
      TG-FTIR and Py-GC/MS. The evolutions of four typical volatile components and the
      distributions of eight product species were scrutinized. A DG-DAEM kinetic model
      was applied to quantify the contributions of two major pyrolytic routes for
      devolatilization during hemicellulose pyrolysis. A mean activation energy of
      150kJ/mol for the formation of volatiles was derived. The thermal stability of
      each bond in four typical fragments of hemicellulose was assessed by DFT study,
      and the deduced decomposition pathways were in agreement with experimental
      analysis. 

PMID- 25958145
TI  - Physico-chemical factors affecting the in vitro stability of phycobiliproteins
      from Phormidium rubidum A09DM.
AB  - The functionality and stability of phycobiliproteins (PBPs) phycoerythrin (PE),
      phycocyanin (PC) and allophycocyanin (APC) were investigated under various
      temperatures, pHs and oxidative stressors. All PBPs were thermostable up to 4-40
      degrees C; however, their concentration decreased rapidly at 60-80 degrees C. The
      maximum stability of all PBPs was in the pH range 6.0-7.0. Decrease in PBPs
      content was found under high acidic (pH 2-4) and alkaline conditions (pH 8-12).
      The oxidizing agent (0.1-0.6%) showed the least effect on the stability of PBPs;
      however, 0.8-1.0% H2O2 caused significant loss of PBPs. Contrary to PE, PC and
      APC was more susceptible to an oxidizing agent. The chromophore associated with
      alpha- and beta-subunit of PBPs and thus, their functionality (fluorescence) was
      severely affected under high temperature (60-80 degrees C), and oxidizing agent,
      as well as low (2-4) and high (8-12) pH. Contrary to PC and APC, functionality of
      PE was surprisingly maintained even at pHs 6-12 and under oxidative stress. 

PMID- 25958146
TI  - Biogas production within the bioethanol production chain: Use of co-substrates
      for anaerobic digestion of sugar beet vinasse.
AB  - Bioethanol production generates large amounts of vinasse, which is suitable for
      biogas production. In this study, the anaerobic digestion of sugar beet vinasse
      was optimised using continuous stirred-tank reactors (CSTR) supplemented either
      with lime fertiliser or with 3% cow manure. In both reactors, the C/N ratio was
      adjusted by adding straw. The biochemical methane potential (BMP) of vinasse was
      267.4+/-4.5LCH4kgVS(-1). Due to the low content of macro- and micronutrients and
      low C/N ratio of vinasse, biogas production failed when vinasse alone was fed to
      the reactor. When co-substrate was added, biogas production achieved very close
      to the BMP of vinasse, being 235.7+/-32.2LCH4kgVS(-1) from the fertiliser
      supplied reactor and 265.2+/-26.8LCH4kgVS(-1) in manure supplied reactor at
      steady state. Anaerobic digestion was the most stable when cow manure was
      supplied to digestion of vinasse. 

PMID- 25958147
TI  - Improving growth rate of microalgae in a 1191m(2) raceway pond to fix CO2 from
      flue gas in a coal-fired power plant.
AB  - CO2 fixation between microalgal biomass and culture solution and the weight ratio
      of biomass consumption at nighttime to biomass growth at daytime were compared in
      an open raceway pond aerated with flue gas from a coal-fired power plant. Average
      daytime sunlight intensity and solution temperature were optimized to improve
      microalgal growth rate and to enhance the efficiency of CO2 fixation. When the
      average daytime solution temperature increased from 12 to 26 degrees C, the rate
      of biomass consumption due to microalgal respiration at nighttime increased from
      6.0 to 7.9g/m(2)/d, which was approximately 25% of the biomass growth rate at
      daytime. Furthermore, when the average daytime sunlight intensity increased from
      39,900 to 88,300lux, CO2 fixation rate in the microalgal biomass increased from
      18.4 to 40.7g/m(2)/d, which was approximately 1/3 of CO2 removal rate from flue
      gas by the microalgal culture system. 

PMID- 25958148
TI  - Investigation of uncertainties associated with the production of n-butanol
      through ethanol catalysis in sugarcane biorefineries.
AB  - This study evaluated the viability of n-butanol production integrated within a
      first and second generation sugarcane biorefinery. The evaluation included a
      deterministic analysis as well as a stochastic approach, the latter using Monte
      Carlo simulation. Results were promising for n-butanol production in terms of
      revenues per tonne of processed sugarcane, but discouraging with respect to
      internal rate of return (IRR). The uncertainty analysis determined there was high
      risk involved in producing n-butanol and co-products from ethanol catalysis. It
      is unlikely that these products and associated production route will be
      financially attractive in the short term without lower investment costs,
      supportive public policies and tax incentives coupled with biofuels' production
      strategies. 

PMID- 25958149
TI  - Biohythane production from marine macroalgae Sargassum sp. coupling dark
      fermentation and anaerobic digestion.
AB  - Potential biohythane production from Sargassum sp. was evaluated in a two stage
      process. In the first stage, hydrogen dark fermentation was performed by
      Caldicellulosiruptor saccharolyticus. Sargassum sp. concentrations (VS) of 2.5,
      4.9 and 7.4gL(-1) and initial inoculum concentrations (CDW) of 0.04 and 0.09gL(
      1) of C. saccharolyticus were used in substrate/inoculum ratios ranging from 28
      to 123. The end products from hydrogen production process were subsequently used
      for biogas production. The highest hydrogen and methane production yields, 91.3+/
      3.3Lkg(-1) and 541+/-10Lkg(-1), respectively, were achieved with 2.5gL(-1) of
      Sargassum sp. (VS) and 0.09gL(-1)of inoculum (CDW). The biogas produced contained
      14-20% of hydrogen. Potential energy production from Sargassum sp. in two stage
      process was estimated in 242GJha(-1)yr(-1). A maximum energy supply of 600EJyr(
      1) could be obtained from the ocean potential area for macroalgae production. 

PMID- 25958150
TI  - Effect of carbon source on biomass growth and nutrients removal of Scenedesmus
      obliquus for wastewater advanced treatment and lipid production.
AB  - The combination of tertiary wastewater treatment and microalgal lipid production
      is considered to be a promising approach to water eutrophication as well as
      energy crisis. To intensify wastewater treatment and microalgal biofuel
      production, the effect of organic and inorganic carbon on algal growth and
      nutrient removal of Scenedesmus obliquus were examined by varying TOC (total
      organic carbon) concentrations of 20-120mgL(-1) in wastewater and feeding CO2
      concentrations in the range of 0.03-15%, respectively. The results showed that
      the maximal biomass and average lipid productivity were 577.6 and 16.7mgL(-1)d(
      1) with 5% CO2 aeration. The total nitrogen, total phosphorus and TOC removal
      efficiencies were 97.8%, 95.6% and 59.1% respectively within 6days when cultured
      with real secondary municipal wastewater. This work further showed that S.
      obliquus could be utilized for simultaneous organic pollutants reduction, N, P
      removal and lipid accumulation. 

PMID- 25958151
TI  - A multi-criteria analysis approach for ranking and selection of microorganisms
      for the production of oils for biodiesel production.
AB  - Oleaginous microorganisms have potential to be used to produce oils as
      alternative feedstock for biodiesel production. Microalgae (Chlorella
      protothecoides and Chlorella zofingiensis), yeasts (Cryptococcus albidus and
      Rhodotorula mucilaginosa), and fungi (Aspergillus oryzae and Mucor plumbeus) were
      investigated for their ability to produce oil from glucose, xylose and glycerol.
      Multi-criteria analysis (MCA) using analytic hierarchy process (AHP) and
      preference ranking organization method for the enrichment of evaluations
      (PROMETHEE) with graphical analysis for interactive aid (GAIA), was used to rank
      and select the preferred microorganisms for oil production for biodiesel
      application. This was based on a number of criteria viz., oil concentration,
      content, production rate and yield, substrate consumption rate, fatty acids
      composition, biomass harvesting and nutrient costs. PROMETHEE selected A. oryzae,
      M. plumbeus and R. mucilaginosa as the most prospective species for oil
      production. However, further analysis by GAIA Webs identified A. oryzae and M.
      plumbeus as the best performing microorganisms. 

PMID- 25958152
TI  - Pharmacological characterization of a tyramine receptor from the southern cattle
      tick, Rhipicephalus (Boophilus) microplus.
AB  - The southern cattle tick (Rhipicephalus (Boophilus) microplus) is a hematophagous
      external parasite that vectors the causative agents of bovine babesiosis or
      cattle tick fever, Babesia bovis and B. bigemina, and anaplasmosis, Anaplasma
      marginale. The southern cattle tick is a threat to the livestock industry in many
      locations throughout the world. Control methods include the use of chemical
      acaricides including amitraz, a formamidine insecticide, which is proposed to
      activate octopamine receptors. Previous studies have identified a putative
      octopamine receptor from the southern cattle tick in Australia and the Americas.
      Furthermore, this putative octopamine receptor could play a role in acaricide
      resistance to amitraz. Recently, sequence data indicated that this putative
      octopamine receptor is probably a type-1 tyramine receptor (TAR1). In this study,
      the putative TAR1 was heterologously expressed in Chinese hamster ovary (CHO-K1)
      cells, and the expressed receptor resulted in a 39-fold higher potency for
      tyramine compared to octopamine. Furthermore, the expressed receptor was strongly
      antagonized by yohimbine and cyproheptadine, and mildly antagonized by mianserin
      and phentolamine. Tolazoline and naphazoline had agonistic or modulatory activity
      against the expressed receptor, as did the amitraz metabolite, BTS-27271;
      however, this was only observed in the presence of tyramine. The southern cattle
      tick's tyramine receptor may serve as a target for the development of anti
      parasitic compounds, in addition to being a likely target of formamidine
      insecticides. 

PMID- 25958153
TI  - Perioperative Care of Children with Eisenmenger Syndrome Undergoing Non-cardiac
      Surgery.
AB  - The Eisenmenger syndrome (ES) is a severe form of pulmonary arterial hypertension
      and arises in congenital heart disease with a systemic-to-pulmonary shunt.
      Patients with ES have multisystem involvement as a result of chronic hypoxemia
      with hematologic, skeletal, renal, and neurologic systems, causing significant
      morbidity and mortality. In contrast to pulmonary arterial hypertension, survival
      prospects are far superior in patients with ES and a growing number of ES
      patients are surviving into adulthood. As a result, many face the prospect of
      incidental surgery. To date, there is no guideline for the perioperative care of
      ES patients in children and limited data available for adult patients. This
      review provides an overview of appropriate measures for the safe perioperative
      care of patients, based on an understanding of the pathophysiological changes
      that occur in ES. 

PMID- 25958154
TI  - A Smartphone Application to Diagnose the Mechanism of Pediatric Supraventricular
      Tachycardia.
AB  - Smartphone applications that record a single-lead ECG are increasingly available.
      We sought to determine the utility of a smartphone application (AliveCor) to
      record supraventricular tachycardia (SVT) and to distinguish atrioventricular
      reentrant tachycardia (AVRT) from atrioventricular nodal reentrant tachycardia
      (AVNRT) in pediatric patients. A prior study demonstrated that interpretation of
      standard event and Holter monitors accurately identifies the tachycardia
      mechanism in only 45 % of recordings. We performed an IRB-approved prospective
      study in pediatric patients undergoing an ablation for SVT. Tracings were
      obtained by placing the smartphone in three different positions on the chest (PI
      horizontal, PII-rotated 60 degrees  clockwise, and PIII-rotated 120 degrees 
      clockwise). Two blinded pediatric electrophysiologists jointly analyzed a pair of
      sinus and tachycardia tracings in each position. Tracings with visible retrograde
      P waves were classified as AVRT. The three positions were compared by Chi-square
      test. Thirty-seven patients (age 13.7 +/- 2.8 years) were enrolled in the study.
      Twenty-four had AVRT, and 13 had AVNRT. One hundred and eight pairs of tracings
      were obtained. The correct diagnosis was made in 27/37 (73 %) with position PI,
      28/37 (76 %) with PII, and 20/34 (59 %) with PIII (p = 0.04 for PII vs. PIII and
      p = NS for other comparisons). A single-lead ECG obtained with a smartphone
      monitor can successfully record SVT in pediatric patients and can predict the SVT
      mechanism at least as well as previously published reports of Holter monitors,
      along with the added convenience of not requiring patients to carry a dedicated
      monitor.

PMID- 25958155
TI  - Global profiling of histone modifications in the polyomavirus BK virion
      minichromosome.
AB  - During polyomavirus infection, the viral DNA adopts histones from host cells and
      forms minichromosomes as an important part of the viral life cycle. However, the
      detailed mechanisms of this histone incorporation remain unclear. Here, we
      profiled the histone posttranslational modifications (PTMs) in BKPyV
      minichromosomes and in the chromatin of BKPyV host cells. Through Triton-acetic
      acid-urea (TAU)-PAGE separation followed by nanoflow liquid chromatography
      coupled with tandem mass spectrometry (LC-MS/MS) analysis, we identified
      different kinds of PTMs on histones from BKPyV minichromosomes and from host
      cells. We observed not only the common PTMs on histones such as acetylation,
      methylation, phosphorylation, ubiquitination, and formylation but also several
      novel PTM sites. Our results also confirmed that the BKPyV minichromosome is
      hyperacetylated. Our detailed histone PTM profiles for the BKPyV minichromosome
      provide insights for future exploration of the underlying mechanisms and
      biological relevance of these histone PTMs. 

PMID- 25958157
TI  - [Real-world data and clinical research: The complement data from randomized
      trials].

PMID- 25958158
TI  - [Suicide risk assessment tools for adults in general medical practice].
AB  - BACKGROUND: It is estimated that almost half of suicide victims have consulted a
      general practitioner during the month preceding their act. The implementation of
      a suicide risk assessment tool validated in primary care is therefore needed in
      general medical practice. OBJECTIVES: To review the suicide risk assessment tools
      for adults, to discuss their validity, and to suggest a pertinent tool which
      could be used in primary care. METHODS: Research into scientific databases
      (keywords: psychiatric status rating scales; tools; questionnaires; risk
      assessment; suicide; attempted suicide; suicidal ideation; primary care; family
      practice; general practice) and into French and English language primary care
      journals. Review of publications and recommendations from health promotion and
      suicide prevention organizations, and from general practice and psychiatry
      learned societies. RESULTS: Two categories of suicide risk assessment tools have
      been found. On one hand, questionnaires aim at predicting suicidal behaviours (or
      their recurrence) using a risk score. They are interesting in research but of
      limited value in clinical practice because of their low specificity and
      individual predictive power. On the other hand, semi-directive interviews unable
      clinicians to explore the three dimensions of suicidality (levels of risk,
      urgency and danger), thus knowing to what extent the patient is suicidal and to
      adopt the appropriate preventive care strategy. Their use in clinical routine is
      highly recommended. The Grille d'estimation de la dangerosite d'un passage a
      l'acte suicidaire is the only interview to have been validated in primary care so
      far. It could be a pertinent tool in general practice. CONCLUSION: Preventing
      suicide in primary care requires the assessment of suicide risk using a semi
      directive interview. We suggest a qualitative study to be carried out in general
      practice on the Grille d'estimation de la dangerosite d'un passage a l'acte
      suicidaire.

PMID- 25958156
TI  - Complete sporogony of Plasmodium relictum (lineage pGRW4) in mosquitoes Culex
      pipiens pipiens, with implications on avian malaria epidemiology.
AB  - Plasmodium relictum (lineage pGRW4) causes malaria in birds and is actively
      transmitted in countries with warm climates and also temperate regions of the New
      World. In Europe, the lineage pGRW4 has been frequently reported in many species
      of Afrotropical migrants after their arrival from wintering grounds, but is rare
      in European resident birds. Obstacles for transmission of this parasite in Europe
      have not been identified. Culex quinquefasciatus is an effective vector of pGRW4
      malaria, but this mosquito is absent from temperate regions of Eurasia. It
      remains unclear if the lineage pGRW4 completes sporogony in European species of
      mosquitoes. Here we compare the sporogonic development of P. relictum (pGRW4) in
      experimentally infected mosquitoes Culex pipiens pipiens form molestus, C.
      quinquefasciatus, and Ochlerotatus cantans. The pGRW4 parasite was isolated from
      a garden warbler Sylvia borin, multiplied, and used to infect laboratory-reared
      Culex spp. and wild-caught Ochlerotatus mosquitoes by allowing them to take blood
      meals on infected birds. The exposed females were maintained at a mean laboratory
      temperature of 19  degrees C, which ranged between 14  degrees C at night and 24 
      degrees C during daytime. They were dissected on intervals to study the
      development of sporogonic stages. Only ookinetes developed in O. cantans;
      sporogonic development was abortive. The parasite completed sporogony in both
      Culex species, with similar patterns of development, and sporozoites were
      reported in the salivary glands 16 days after infection. The presence of
      sporogonic stages of the lineage pGRW4 in mosquitoes was confirmed by PCR-based
      testing of (1) the sporozoites present in salivary glands and (2) the single
      oocysts, which were obtained by laser microdissection from infected mosquito
      midguts. This study shows that P. relictum (pGRW4) completes sporogony in C. p.
      pipiens at relatively low temperatures. We conclude that there are no
      restrictions for spreading this bird infection in Europe from the point of view
      of vector availability and temperature necessary for sporogony. Other factors
      should be considered and were discussed for the explanation of rare reports of
      this malaria parasite in Europe.

PMID- 25958159
TI  - Macro and micro structures in the dorsal anterior cingulate cortex contribute to
      individual differences in self-monitoring.
AB  - Individual differences in self-monitoring, which are the capability to adjust
      behavior to adapt to social situations, influence a wide range of social
      behaviors. However, understanding of focal differences in brain structures
      related to individual self-monitoring is minimal, particularly when micro and
      macro structures are considered simultaneously. The present study investigates
      the relationship between self-monitoring and brain structure in a relatively
      large sample of young adults. Voxel-based morphometry (VBM) revealed a
      significant positive correlation between self-monitoring and gray matter volume
      in the dorsal cingulate anterior cortex (dACC), dorsal lateral prefrontal cortex
      (DLPFC), and bilateral ventral striatum (VS). Further analysis revealed a
      significant negative correlation between self-monitoring and white matter (WM)
      integrity, as indexed by fractional anisotropy (FA) in the anterior cingulum
      (ACG) bundle. Moreover, there was a significant positive correlation between self
      monitoring and mean radius diffusion (RD). These results shed light on the
      structural neural basis of variation in self-monitoring.

PMID- 25958160
TI  - Primary epidermoid cysts of the mastoid: clinical and treatment implications.
AB  - Epidermoid cysts of the temporal bone are extremely rare and such lesions arising
      in isolation within the mastoid bone have never been reported in literature. We
      report and describe the first two unique cases of primary epidermoid cysts
      arising in the mastoid bone. Of the two cases, one presented with progressive
      headache and imbalance and the other with unilateral hearing loss and tinnitus.
      Both cases needed CT and MRI scans and needed surgical management. We review the
      clinical presentations, histology, pathogenesis, radiological findings and
      management of these challenging cases. The diagnosis of an epidermoid cyst is
      based on clinical presentation, physical examination and especially the
      radiological, histological and intraoperative findings. Total removal of the
      lesion along with its capsule is recommended to prevent recurrence and to allow
      for a good long-term prognosis.

PMID- 25958161
TI  - Craniocervical junction involvement in ankylosing spondylitis.
AB  - PURPOSE: Available studies of craniocervical junction (CCJ) involvement in
      ankylosing spondylitis (AS) are based on conventional radiography, which has
      limited ability in the definition of many elements of the CCJ. The goal of the
      present study was to describe the spectrum of computed tomography (CT) findings
      in the CCJ in a cohort of patients with AS. METHODS: CT scans of the cervical
      spine of 11 patients with AS and 33 control subjects were reviewed, and imaging
      findings related to the CCJ were assessed. The standard anatomic intervals
      describing the CCJ were measured and compared to accepted normal standards.
      Findings representing pathology were described, categorized by localization, and
      relation to joints or ligaments of the CCJ. RESULTS: All AS patients were males
      with median age of 48 years and median disease duration of 20 years. The
      calculated median-modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) for
      the cervical spine was 8.5 ranging from 0 to 27. Disease-related changes in one
      or more elements of the CCJ were detected in all patients. Atlanto-occipital
      joints were involved in 8 patients, while 3 patients had disease of the atlanto
      dental articulation. Enthesopathy of the CCJ was observed in 7 patients.
      CONCLUSIONS: The CCJ is frequently involved in AS patients with advanced disease
      and may be independent on the mSASSS. Both articulations and ligaments of CCJ may
      be affected in AS patients.

PMID- 25958162
TI  - Indian hedgehog contributes to human cartilage endplate degeneration.
AB  - PURPOSE: To determine the role of Indian hedgehog (Ihh) signaling in human
      cartilage endplate (CEP) degeneration. METHODS: CEP-degenerated tissues from
      patients with Modic I or II changes (n = 9 and 45, respectively) and normal
      tissues from vertebral burst fracture patients (n = 17) were collected. Specimens
      were either cut into slices for organ culture ex vivo or digested to isolate
      chondrocytes for cell culture in vitro. Ihh expression and the effect of Ihh on
      cartilage degeneration were determined by investigating degeneration markers in
      this study. RESULTS: Ihh expression and cartilage degeneration markers
      significantly increased in the Modic I and II groups. The expression of cartilage
      degeneration markers was positively correlated with degeneration severity. Gain
      of-function for Ihh promoted expression of cartilage degeneration markers in
      vitro, while loss-of-function for Ihh inhibited their expression both in vitro
      and ex vivo. CONCLUSIONS: These findings demonstrated that Ihh promotes CEP
      degeneration. Blocking Ihh pathway has potential clinical usage for attenuating
      CEP degeneration.

PMID- 25958164
TI  - Evidence of a hemolymph-born factor that induces onset of maturation in Manduca
      sexta larvae.
AB  - Insect metamorphosis is a complex developmental transition determined and
      coordinated by hormonal signaling that begins at a critical weight late in the
      larval phase of life. Even though this hormonal signaling is well understood in
      insects, the internal factors that are assessed at the critical weight and that
      drive commitment to metamorphosis have remained unresolved in most species. The
      critical weight may represent either an autonomous decision by the neuroendocrine
      system without input from other developing larval tissues, or an assessment of
      developmental thresholds occurring throughout the body that are then integrated
      by the neuroendocrine tissues. The latter hypothesis predicts that there could be
      one or more developmental threshold signals that originate from developing
      tissues and ultimately induce the onset of metamorphosis. However, there is no
      evidence for such a signal in the organisms for which the critical weight is well
      described. Here we test for the evidence of this factor in Manduca sexta
      (Lepidoptera: Sphingidae) by transferring hemolymph from individuals that are
      either post- or pre-critical weight into pre-critical weight 5(th) instar larvae.
      We found that hemolymph from a post-critical weight donor induces a shortening of
      development time, though the mass at pupation is unaffected. This suggests that
      metamorphic commitment occurring at the critical weight is at least partially
      coordinated by signaling from developing tissues via a hemolymph-borne signaling
      factor. 

PMID- 25958163
TI  - Hirudin promotes angiogenesis by modulating the cross-talk between p38 MAPK and
      ERK in rat ischemic skin flap tissue.
AB  - Hirudin's ability to increase angiogenesis in ischemic flap tissue and improve
      the flaps survival has been demonstrated in our previous studies. However, the
      knowledge about hirudin functional role in angiogenesis is still limited. In the
      present study, we investigate the effects of locally injected hirudin on the
      expression of VEGF, endostatin and thrombospondin-1 (TSP-1) using rat model.
      Caudally based dorsal skin flaps were created and were treated with hirudin or
      normal saline. Result showed that the flap survival was improved by hirudin
      treatment relative to the control. Treatment of flaps with hirudin exerted
      significant angiogenic effect as evidenced by increased VEGF expression and
      reduced endostatin and TSP-1 production (p<0.01), and promoted neovascularization
      (microvascular density, p<0.01). Moreover, hirudin treatment increased the ERK1/2
      phosphorylation, while attenuated the phosphorylation of p38 MAPK, and the
      addition of thrombin could reverse these effects of hirudin on ERK1/2 and p38
      MAPK activity. The MEK inhibitor blocked the hirudin-induced VEGF expression, and
      the p38 MAPK inhibitor attenuated the thrombin-induced TSP-1 expression.
      Furthermore, a specific inhibitor of p38 MAPK activates ERK1/2 in ischemic flaps,
      suggesting that cross-talk between p38 MAPK and ERK might exist in rat ischemic
      flap tissue. Moreover, either the hirudin or SCH79797 (PAR1 antagonist) could
      attenuate the p38 MAPK phosphorylation and increases the ERK1/2 phosphorylation,
      indicating that the cross-talk between p38 MAPK and ERK1/2 modulated by
      thrombin/PAR1 signaling may participate in the process of hirudin-stimulated
      ERK1/2 signaling. In conclusion, these observations suggest that hirudin exerts
      its angiogenesis effect by regulating the expression of angiogenic and
      antiangiogenic factors via a cross-talk of p38 MAPK-ERK pathway. 

PMID- 25958165
TI  - Apoptosis in mammalian oocytes: a review.
AB  - Apoptosis causes elimination of more than 99% of germ cells from cohort of ovary
      through follicular atresia. Less than 1% of germ cells, which are culminated in
      oocytes further undergo apoptosis during last phases of oogenesis and depletes
      ovarian reserve in most of the mammalian species including human. There are
      several players that induce apoptosis directly or indirectly in oocytes at
      various stages of meiotic cell cycle. Premature removal of encircling granulosa
      cells from immature oocytes, reduced levels of adenosine 3',5'-cyclic
      monophosphate and guanosine 3',5'-cyclic monophosphate, increased levels of
      calcium (Ca(2+)) and oxidants, sustained reduced level of maturation promoting
      factor, depletion of survival factors, nutrients and cell cycle proteins, reduced
      meiotic competency, increased levels of proapoptotic as well as apoptotic factors
      lead to oocyte apoptosis. The BH3-only proteins also act as key regulators of
      apoptosis in oocyte within the ovary. Both intrinsic (mitochondria-mediated) as
      well as extrinsic (cell surface death receptor-mediated) pathways are involved in
      oocyte apoptosis. BID, a BH3-only protein act as a bridge between both apoptotic
      pathways and its cleavage activates cell death machinery of both the pathways
      inside the follicular microenvironment. Oocyte apoptosis leads to the depletion
      of ovarian reserve that directly affects reproductive outcome of various mammals
      including human. In this review article, we highlight some of the important
      players and describe the pathways involved during oocyte apoptosis in mammals.

PMID- 25958166
TI  - Attenuation of aortic aneurysms with stem cells from different genders.
AB  - BACKGROUND: No medical therapies are yet available to slow abdominal aortic
      aneurysm (AAA) growth. This study sought to investigate the effect of different
      genders of bone marrow-derived mesenchymal stem cells (MSC) on AAA growth in a
      murine AAA model. Given the decreased rate of AAA in women, it is hypothesized
      that female MSC would attenuate AAA growth more so than male MSC. MATERIALS AND
      METHODS: Aortas of 8-10-wk-old male C57Bl/6 mice were perfused with purified
      porcine pancreatic elastase to induce AAA formation. Bone marrow-derived MSC from
      male and female mice were dosed via tail vein injection (3 million cells per
      dose, 500 MUL of volume per injection) on postaortic perfusion days 1, 3, and 5.
      Aortas were harvested after 14 d. RESULTS: Mean aortic dilation in the elastase
      group was 121 +/- 5.2% (mean +/- standard error of the mean), while male MSC
      inhibited AAA growth (87.8 +/- 6.9%, P = 0.008) compared with that of elastase.
      Female MSC showed the most marked attenuation of AAA growth (75.2 +/- 8.3% P =
      0.0004). Proinflammatory cytokines tumor necrosis factor alpha, interleukin
      1beta, and monocyte chemotactic protein-1 (MCP-1) were only decreased in tissues
      treated with female MSC (P = 0.017, P = 0.001, and P < 0.0001, respectively, when
      compared with elastase). CONCLUSIONS: These data exhibit that female MSC more
      strongly attenuate AAA growth in the murine model. Furthermore, female MSC and
      male MSC inhibit proinflammatory cytokines at varying levels. The effects of MSC
      on aortic tissue offer a promising insight into biologic therapies for future
      medical treatment of AAAs in humans.

PMID- 25958167
TI  - Continuous topical irrigation for severely infected wound healing.
AB  - BACKGROUND: Management of severely infected wounds is a formidable challenge. The
      pilot prospective cohort study is to investigate the influence of continuous
      topical irrigation (CTI) on the outcomes of severely infected wounds. METHODS:
      This pilot study was performed on 17 patients with a single severely infected
      wound treated with CTI, compared with a control group of 15 patients treated with
      standard of care from January 2011-January 2013. Bates-Jensen wound assessment
      tool severity scores and the clinical outcomes were recorded. Profiles of
      cytokines and/or proteinase in wound fluid were quantified weekly. RESULTS:
      Comparing with the control, the CTI-treated patients required fewer days for
      wound infection clearance (8 +/- 2 versus 19 +/- 5 d, P < 0.001), had wounds
      closed earlier (17 +/- 4 versus 36 +/- 7 d, P < 0.001), and had fewer inhospital
      stay days (23 +/- 5 versus 42 +/- 8 d, P < 0.001). Bates-Jensen wound assessment
      tool severity scorings, proinflammatory cytokines (tumor necrosis factor-alpha,
      interleukin 1beta, and interleukin 6), and matrix metalloproteinase-8 were
      significantly decreased in response to CTI. CONCLUSIONS: This pilot study
      demonstrates that CTI improves severely infected wound healing through partly
      inhibiting proinflammatory cytokines and improving tissue regeneration.

PMID- 25958168
TI  - Body mass index predicts operative time in elective colorectal procedures.
AB  - BACKGROUND: Obesity currently affects more than a third of the United States
      population and is associated with increased surgical complications. Compared to
      all other subspecialties, colorectal surgery is the most affected by the
      increasing trend in obese surgical patients. Operative time has been found to
      have the greatest impact on hospital costs and physician workload. This study was
      conducted to determine whether obesity has a direct impact on operative time in
      elective colorectal procedures using a high-powered, nationally representative
      patient sample. METHODS: A retrospective analysis was conducted on 45,362
      patients who underwent open and laparoscopic ileocolic resections, partial
      colectomies, and low pelvic anastomoses using American College of Surgeons
      National Surgical Quality Improvement Program data from 2005-2009. Operative time
      was the main outcome variable, whereas body mass index (BMI) was the main
      independent variable. BMI was divided into three classes as follows: normal
      (<25), overweight and/or obese (25-35), and morbidly obese (>35). A univariate
      linear model was used to analyze the relationship while controlling for
      confounding factors such as demographics and preoperative conditions. Statistical
      significance was established at P <= 0.05. RESULTS: Morbidly obese patients were
      found to have longer operative times than did normal patients across each
      individual colorectal procedure (P < 0.001), ranging from a mean difference of
      17.8 min for open ileocolic resections to 56.6 min for laparoscopic low pelvic
      anastomoses with colostomies. CONCLUSIONS: BMI, as an objective measure of
      obesity, is a direct, statistically significant independent predictor of
      operative time across elective colorectal procedures.

PMID- 25958169
TI  - An in vitro evaluation of the responses of human osteoblast-like SaOs-2 cells on
      SLA titanium surfaces irradiated by different powers of CO2 lasers.
AB  - Bacterial biofilms have been identified as the primary etiological factor for the
      development and progression of peri-implantitis. Lasers have been shown to remove
      bacterial plaque from titanium surfaces effectively and can restore its
      biocompatibility without damaging these surfaces. Therefore, the aim of this
      study was to evaluate the responses (i.e., the cell viability and morphology) of
      human osteoblast-like SaOs-2 cells to sandblasted, large grit, and acid-etched
      (SLA) titanium surfaces irradiated by CO2 lasers at two different power outputs.
      A total of 24 SLA disks were randomly radiated by CO2 lasers at either 6 W (group
      1, 12 disks) or 8 W (group 2, 12 disks). Non-irradiated disks were used as a
      control group (four disks). The cell viability rates of the SaOs-2 cells in the
      control and study groups (6 and 8 W) were 0.33 +/- 0.00, 0.24 +/- 0.11, and
      0.2372 +/- 0.09, respectively (P < 0.6). Cells with cytoplasmic extensions and
      spreading morphology were most prominent in the control group (141.00 +/- 29.00),
      while in the study groups (6 and 8 W), the number of cells with such morphology
      was 60.40 +/- 26.00 and 35.20 +/- 5.40, respectively (P < 0.005). Within the
      limits of this study, it may be concluded that the use of CO2 lasers with the
      aforementioned setting parameters could not be recommended for decontamination of
      SLA titanium surfaces. 

PMID- 25958172
TI  - Effect of femtosecond laser beam angle on bond strength of zirconia-resin cement.
AB  - Yttrium-stabilized tetragonal zirconia polycrystalline (Y-TZP) ceramic is widely
      used as an all-ceramic core material because of its enhanced mechanical and
      aesthetic properties. The bond strength of Y-TZP restorations affects long-term
      success; hence, surface treatment is required on ceramic boundaries. This study
      evaluated the effect of different laser beam angles on Y-TZP-resin cement shear
      bond strength (SBS). Forty plates of Y-TZP ceramics were randomly assigned to
      four groups (n = 10). A femtosecond amplifier laser pulse was applied on Y-TZP
      surface with different incidence angles (90 degrees , 75 degrees , 60 degrees ,
      45 degrees ). The resin cement was adhered onto the zirconia surfaces. The SBS of
      each sample was measured using universal testing machine at crosshead speed of 1
      mm/min. The SBS was analyzed through one-way analysis of variance (ANOVA)/Tukey
      tests. The results showed that the degree of laser beam angle affects the SBS of
      resin cement to Y-TZP. The laser beam was applied to a surface with a 45 degrees 
      angle which resulted in significantly higher SBS (18.2 +/- 1.43 MPa) than other
      groups (at 90 degrees  angulation (10.79 +/- 1.8 MPa), at 75 degrees  (13.48 +/-
      1.2 MPa) and at 60 degrees  (15.85 +/- 0.81 MPa); p < 0.001). This study shows
      that decreasing of the angle between the ceramic surface and the laser beam
      increased the SBS between the resin cement and the ceramic material, as well as
      the orifice. 

PMID- 25958173
TI  - District-level variations in childhood immunizations in India: The role of socio
      economic factors and health infrastructure.
AB  - Routine childhood immunizations against measles and DPT are part of the World
      Health Organization's (WHO) Expanded Program on Immunization (EPI) set up in
      1974, with the aim of reducing childhood morbidity and mortality. Despite this,
      immunization rates are sub-optimal in developing countries such as India, with
      wide heterogeneity observed across districts and socio-economic characteristics.
      The aim of this paper is to examine district-level variations in the propensity
      to vaccinate a child in India for measles and DPT3, and analyse the extent to
      which these immunizations are given age-inappropriately, either prematurely or
      delayed. The present study uses data from the Indian District Level Household
      Survey (DLHS-3) collected in 2008, and the final sample contains detailed
      information on 42157 children aged between 12 and 60 months, across 549 Indian
      districts for whom we have complete information on immunization history. Our
      empirical study analyses: (i) the district-level average immunization rates for
      measles and DPT3, and (ii) the extent to which these immunizations have been
      given age-appropriately. A key contribution of this paper is that we link the
      household-level data at the district level to data on availability and proximity
      to health infrastructure and district-level socio-economic factors. Our results
      show that after controlling for an array of socio-economic characteristics,
      across all our models, the district's income per capita is a strong predictor of
      better immunization outcomes for children. Mother's education level at the
      district-level has a statistically significant and positive influence on
      immunization outcomes across all our models. 

PMID- 25958170
TI  - Low-level laser therapy (LLLT) associated with aerobic plus resistance training
      to improve inflammatory biomarkers in obese adults.
AB  - Recently, investigations suggest the benefits of low-level laser (light) therapy
      (LLLT) in noninvasive treatment of cellulite, improvement of body countering, and
      control of lipid profile. However, the underlying key mechanism for such
      potential effects associated to aerobic plus resistance training to reduce body
      fat and inflammatory process, related to obesity in women still unclear. The
      purpose of the present investigation was to evaluate the effects of combined
      therapy of LLLT and aerobic plus resistance training in inflammatory profile and
      body composition of obese women. For this study, it involved 40 obese women with
      age of 20-40 years. Inclusion criteria were primary obesity and body mass index
      (BMI) greater than 30 kg/m(2) and less than 40 kg/m(2). The voluntaries were
      allocated in two different groups: phototherapy group and SHAM group. The
      interventions consisted on physical exercise training and application of
      phototherapy (808 nm), immediately after the physical exercise, with special
      designed device. Proinflammatory/anti-inflammatory adipokines were measured. It
      was showed that LLLT associated to physical exercise is more effective than
      physical exercise alone to increase adiponectin concentration, an anti
      inflammatory adipokine. Also, it showed reduced values of neck circumference
      (cm), insulin concentration (MUU/ml), and interleukin-6 (pg/ml) in LLLT group. In
      conclusion, phototherapy can be an important tool in the obesity, mostly
      considering its potential effects associated to exercise training in attenuating
      inflammation in women, being these results applicable in the clinical practices
      to control related risk associated to obesity. 

PMID- 25958174
TI  - Comparison of the tuberculin test, histopathological examination, and bacterial
      culture for the diagnosis of tuberculosis (Mycobacterium bovis) in buffaloes
      (Bubalus bubalis) in Brazil.
AB  - Tuberculosis is a disease with a great zoonotic potential. It is considered a
      major obstacle to cattle production and is responsible for severe losses in
      several production systems. A comparative cervical test (CCT) was performed in
      1140 buffaloes from different mesoregions of the state of Para, Brazil, with the
      aim of comparing the sensitivity and specificity of CCT with histopathological
      examination and bacterial culture. Of the animals tested using CCT, 4.65%
      (53/1140) were positive, 2.98% (34/1140) were inconclusive, and 92.36%
      (1053/1140) were negative. Among the 168 sacrificed animals, 33 were positive, 18
      were inconclusive, and 117 were negative by CCT, and samples from the sacrificed
      animals were collected for histopathological examination and bacterial culture. A
      qualitative evaluation of the tuberculin test was performed by comparing the test
      results with the histopathological and bacteriological results. The latter two
      tests yielded a prevalence of 4.16%, a sensitivity of 71.43%, and a specificity
      of 82.61%. Based on these results, we concluded that CCT yielded satisfactory
      results and can be applied in diagnostic studies in buffaloes. The prevalence
      rate obtained using three distinct diagnostic methods suggests that Mycobacterium
      bovis was present in a few animals in the population evaluated.

PMID- 25958175
TI  - Assessment of the sustainability of dual-purpose farms by the IDEA method in the
      subtropical area of central Mexico.
AB  - The objective of this study was to assess the sustainability of 10 dual-purpose
      cattle farms in a subtropical area of central Mexico. The IDEA method
      (Indicateurs de Durabilite des Exploitations Agricoles) was applied, which
      includes the agroecological, socio-territorial and economic scales (scores from 0
      to 100 points per scale). A sample of 47 farms from a total of 91 registered in
      the local livestock growers association was analysed with principal component
      analysis and cluster analysis. From results, 10 farms were selected for the in
      depth study herein reported, being the selection criterion continuous milk
      production throughout the year. Farms had a score of 88 and 86 points for the
      agroecological scale in the rainy and dry seasons. In the socio-territorial
      scale, scores were 73 points for both seasons, being the component of employment
      and services the strongest. Scores for the economic scale were 64 and 56 points
      for the rainy and dry seasons, respectively, when no economic cost for family
      labour is charged, which decreases to 59 and 45 points when an opportunity cost
      for family labour is considered. Dual-purpose farms in the subtropical area of
      central Mexico have a medium sustainability, with the economic scale being the
      limiting factor, and an area of opportunity. 

PMID- 25958176
TI  - Delayed upper extremity paresthesia post permanent implantation of five lead
      spinal cord stimulator for low back and lower extremity pain: A case report.

PMID- 25958177
TI  - Changes of Root Length and Root-to-Crown Ratio after Apical Surgery: An Analysis
      by Using Cone-beam Computed Tomography.
AB  - INTRODUCTION: Apical surgery is an important treatment option for teeth with post
      treatment periodontitis. Although apical surgery involves root-end resection, no
      morphometric data are yet available about root-end resection and its impact on
      the root-to-crown ratio (RCR). The present study assessed the length of
      apicectomy and calculated the loss of root length and changes of RCR after apical
      surgery. METHODS: In a prospective clinical study, cone-beam computed tomography
      scans were taken preoperatively and postoperatively. From these images, the crown
      and root lengths of 61 roots (54 teeth in 47 patients) were measured before and
      after apical surgery. Data were collected relative to the cementoenamel junction
      (CEJ) as well as to the crestal bone level (CBL). One observer took all
      measurements twice (to calculate the intraobserver variability), and the means
      were used for further analysis. The following parameters were assessed for all
      treated teeth as well as for specific tooth groups: length of root-end resection
      and percentage change of root length, preoperative and postoperative RCRs, and
      percentage change of RCR after apical surgery. RESULTS: The mean length of root
      end resection was 3.58 +/- 1.43 mm (relative to the CBL). This amounted to a loss
      of 33.2% of clinical and 26% of anatomic root length. There was an overall
      significant difference between the tooth groups (P < .05). There was also a
      statistically significant difference comparing mandibular and maxillary teeth (P
      < .05), but not for incisors/canines versus premolars/molars (P = .125). The mean
      preoperative and postoperative RCRs (relative to CEJ) were 1.83 and 1.35,
      respectively (P < .001). With regard to the CBL reference, the mean preoperative
      and postoperative RCRs were 1.08 and 0.71 (CBL), respectively (P < .001). The
      calculated changes of RCR after apical surgery were 24.8% relative to CEJ and
      33.3% relative to CBL (P < .001). Across the different tooth groups, the mean RCR
      was not significantly different (P = .244 for CEJ and 0.114 for CBL).
      CONCLUSIONS: This CBCT-based study demonstrated that the RCR is significantly
      changed after root-end resection in apical surgery irrespective of the clinical
      (CBL) or anatomic (CEJ) reference levels. The lowest, and thus clinically most
      critical, postoperative RCR was observed in maxillary incisors. Future clinical
      studies need to show the impact of resection length and RCR changes on the
      outcome of apical surgery.

PMID- 25958178
TI  - Antibacterial Properties Associated with Chitosan Nanoparticle Treatment on Root
      Dentin and 2 Types of Endodontic Sealers.
AB  - INTRODUCTION: The aim of this study was to evaluate the efficacy of carboxymethyl
      chitosan (CMCS) and chitosan nanoparticles (CNps) to inactivate bacteria and
      prevent biofilm formation at sealer-dentin interfaces. METHODS: The study was
      divided into 3 stages: first stage, the experiment was conducted to analyze the
      antibacterial properties of CMCS in different formulations against biofilms;
      second stage, direct-contact and membrane-restricted methods were used to
      evaluate the antibacterial properties of an epoxy resin (ThermaSeal Plus;
      Dentsply Tulsa Dental, Tulsa, OK) and calcium silicate (MTA Fillapex; Angelus SA,
      Londrina, PR, Brazil) based-sealers with or without CNps; and third stage,
      biofilm formation at the sealer dentin interfaces of root dentin treated with
      CMCS and filled with gutta-percha and CNp incorporated sealer were analyzed after
      1- and 4-week aging periods. The samples were treated and filled as follows: (1)
      distilled water: unaltered sealer (control group), (2) CMCS: sealer+CNps (CMCS
      group), and (3) CMCS/rose bengal: sealer+CNps (CMCS/RB group). Enterococcus
      faecalis was used to infect all the samples. Microbiological and microscopic
      analyses were used to assess the antibacterial characteristics. RESULTS: CMCS
      based treatments effectively killed bacteria adherent on root dentin (P < .05).
      The addition of CNps to ThermaSeal enhanced its antibacterial ability by direct
      contact and membrane-restricted tests (P < .05). The CNp incorporation
      significantly increased the antibacterial efficacy of root canal sealers even
      after a 4-week aging time (P < .05). CONCLUSIONS: This study highlighted the
      ability of CMCS to disinfect root canal dentin and inhibit bacterial adhesion.
      CNps in root canal sealers are capable of maintaining their antibacterial
      activity even after prolonged aging.

PMID- 25958179
TI  - A First Step in De Novo Synthesis of a Living Pulp Tissue Replacement Using
      Dental Pulp MSCs and Tissue Growth Factors, Encapsulated within a Bioinspired
      Alginate Hydrogel.
AB  - INTRODUCTION: A living, self-supporting pulp tissue replacement in vitro and for
      transplantation is an attractive yet unmet bioengineering challenge. Our aim is
      to create 3-dimensional alginate-based microenvironments that replicate the shape
      of gutta-percha and comprise key elements for the proliferation of progenitor
      cells and the release of growth factors. METHODS: An RGD-bearing alginate
      framework was used to encapsulate dental pulp stem cells and human umbilical vein
      endothelial cells in a ratio of 1:1. The alginate hydrogel also retained and
      delivered 2 key growth factors, vascular endothelial growth factor-121 and
      fibroblast growth factor, in a sufficient amount to induce proliferation. A
      method was then devised to replicate the shape of gutta-percha using RGD alginate
      within a custom-made mold of thermoresponsive N-isopropylacrylamide. Plugs of
      alginate containing different permutations of growth factor-based encapsulates
      were tested and evaluated for viability, proliferation, and release kinetics
      between 1 and 14 days. RESULTS: According to scanning electron microscopic and
      confocal microscopic observations, the encapsulated human endothelial cells and
      dental pulp stem cell distribution were frequent and extensive throughout the
      length of the construct. There were also high levels of viability in all test
      environments. Furthermore, cell proliferation was higher in the growth factor
      based groups. Growth factor release kinetics also showed significant differences
      between them. Interestingly, the combination of vascular endothelial growth
      factor and fibroblast growth factor synergize to significantly up-regulate cell
      proliferation. CONCLUSIONS: RGD-alginate scaffolds can be fabricated into shapes
      to fill the pulp space by simple templating. The addition of dual growth factors
      to cocultures of stem cells within RGD-alginate scaffolds led to the creation of
      microenvironments that significantly enhance the proliferation of dental pulp
      stem cell/human umbilical vein endothelial cell combinations.

PMID- 25958180
TI  - Chromosomal characteristics and distribution of rDNA sequences in the brook trout
      Salvelinus fontinalis (Mitchill, 1814).
AB  - Brook trout Salvelinus fontinalis (Mitchill, 1814) chromosomes have been analyzed
      using conventional and molecular cytogenetic techniques enabling characteristics
      and chromosomal location of heterochromatin, nucleolus organizer regions (NORs),
      ribosomal RNA-encoding genes and telomeric DNA sequences. The C-banding and
      chromosome digestion with the restriction endonucleases demonstrated distribution
      and heterogeneity of the heterochromatin in the brook trout genome. DNA sequences
      of the ribosomal RNA genes, namely the nucleolus-forming 28S (major) and non
      nucleolus-forming 5S (minor) rDNAs, were physically mapped using fluorescence in
      situ hybridization (FISH) and primed in situ labelling. The minor rDNA locus was
      located on the subtelo-acrocentric chromosome pair No. 9, whereas the major rDNA
      loci were dispersed on 14 chromosome pairs, showing a considerable inter
      individual variation in the number and location. The major and minor rDNA loci
      were located at different chromosomes. Multichromosomal location (3-6 sites) of
      the NORs was demonstrated by silver nitrate (AgNO3) impregnation. All Ag-positive
      i.e. active NORs corresponded to the GC-rich blocks of heterochromatin. FISH with
      telomeric probe showed the presence of the interstitial telomeric site (ITS)
      adjacent to the NOR/28S rDNA site on the chromosome 11. This ITS was presumably
      remnant of the chromosome rearrangement(s) leading to the genomic redistribution
      of the rDNA sequences. Comparative analysis of the cytogenetic data among several
      related salmonid species confirmed huge variation in the number and the
      chromosomal location of rRNA gene clusters in the Salvelinus genome. 

PMID- 25958182
TI  - Indomethacin induces endoplasmic reticulum stress, but not apoptosis, in the rat
      kidney.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in clinical
      practice. However, their use is often associated with adverse effects in the
      gastrointestinal tract and kidney. Our earlier work with indomethacin, a
      prototype NSAID, has shown that it induced oxidative stress in the kidney in
      rats, an event that has been postulated to contribute to pathogenesis of its
      adverse effects in this organ. Endoplasmic reticulum (ER) stress responses have
      been shown to occur in response to oxidative stress. We investigated whether this
      occurred in the rat kidney, in response to indomethacin. For this, Wistar rats
      were orally gavaged with indomethacin (20mg/kg). Markers of ER stress were
      studied in the kidneys 1, 12 and 24h later. GRP78, p-PERK and nuclear sXBP-1, all
      markers of ER stress, were found to be increased in the rat kidney at 12h, in
      response to indomethacin; levels of these markers fell by 24h. The effects seen
      at 12h were attenuated by pre-treatment with zinc, a known anti-oxidant, which
      has earlier been shown to ameliorate indomethacin-induced oxidative stress.
      Activation of an ER stress response was not associated with induction of
      apoptosis, as measured by markers of apoptosis such as release of cytochrome c
      from mitochondria into the cytosol, activation of caspases 3 and 9, cleavage of
      poly-ADP ribose polymerase and the presence of DNA laddering. We conclude that
      indomethacin-induced oxidative stress activated ER stress, but did not lead to
      apoptosis in the rat kidney. 

PMID- 25958183
TI  - Humoral and Cellular Immune Response in Canine Hypothyroidism.
AB  - Hypothyroidism is one of the most common endocrine diseases in dogs and is
      generally considered to be autoimmune in nature. In human hypothyroidism, the
      thyroid gland is destroyed by both cellular (i.e. autoreactive helper and
      cytotoxic T lymphocytes) and humoral (i.e. autoantibodies specific for
      thyroglobulin, thyroxine and triiodothyronine) effector mechanisms. Other
      suggested factors include impaired peripheral immune suppression (i.e. the
      malfunction of regulatory T cells) or an additional pro-inflammatory effect of T
      helper 17 lymphocytes. The aim of this study was to evaluate immunological
      changes in canine hypothyroidism. Twenty-eight clinically healthy dogs, 25
      hypothyroid dogs without thyroglobulin antibodies and eight hypothyroid dogs with
      these autoantibodies were enrolled into the study. There were alterations in
      serum proteins in hypothyroid dogs compared with healthy controls (i.e. raised
      concentrations of alpha-globulins, beta2- and gamma-globulins) as well as higher
      concentration of acute phase proteins and circulating immune complexes.
      Hypothyroid animals had a lower CD4:CD8 ratio in peripheral blood compared with
      control dogs and diseased dogs also had higher expression of interferon gamma
      (gene and protein expression) and CD28 (gene expression). Similar findings were
      found in both groups of hypothyroid dogs. Canine hypothyroidism is therefore
      characterized by systemic inflammation with dominance of a cellular immune
      response. 

PMID- 25958184
TI  - Bacterial Zoonoses Transmitted by Household Pets: State-of-the-Art and Future
      Perspectives for Targeted Research and Policy Actions.
AB  - The close contact between household pets and people offers favourable conditions
      for bacterial transmission. In this article, the aetiology, prevalence,
      transmission, impact on human health and preventative measures are summarized for
      selected bacterial zoonoses transmissible by household pets. Six zoonoses
      representing distinct transmission routes were selected arbitrarily based on the
      available information on incidence and severity of pet-associated disease caused
      by zoonotic bacteria: bite infections and cat scratch disease (physical
      injuries), psittacosis (inhalation), leptospirosis (contact with urine), and
      campylobacteriosis and salmonellosis (faecal-oral ingestion). Antimicrobial
      resistance was also included due to the recent emergence of multidrug-resistant
      bacteria of zoonotic potential in dogs and cats. There is a general lack of data
      on pathogen prevalence in the relevant pet population and on the incidence of
      human infections attributable to pets. In order to address these gaps in
      knowledge, and to minimize the risk of human infection, actions at several levels
      are recommended, including: (1) coordinated surveillance of zoonotic pathogens
      and antimicrobial resistance in household pets, (2) studies to estimate the
      burden of human disease attributable to pets and to identify risk behaviours
      facilitating transmission, and (3) education of those in charge of pets, animal
      caretakers, veterinarians and human medical healthcare practitioners on the
      potential zoonotic risks associated with exposure to pets. Disease-specific
      recommendations include incentives to undertake research aimed at the development
      of new diagnostic tests, veterinary-specific antimicrobial products and vaccines,
      as well as initiatives to promote best practices in veterinary diagnostic
      laboratories and prudent antimicrobial usage. 

PMID- 25958185
TI  - Chemical communication in the gut: Effects of microbiota-generated metabolites on
      gastrointestinal bacterial pathogens.
AB  - Gastrointestinal pathogens must overcome many obstacles in order to successfully
      colonize a host, not the least of which is the presence of the gut microbiota,
      the trillions of commensal microorganisms inhabiting mammals' digestive tracts,
      and their products. It is well established that a healthy gut microbiota provides
      its host with protection from numerous pathogens, including Salmonella species,
      Clostridium difficile, diarrheagenic Escherichia coli, and Vibrio cholerae.
      Conversely, pathogenic bacteria have evolved mechanisms to establish an infection
      and thrive in the face of fierce competition from the microbiota for space and
      nutrients. Here, we review the evidence that gut microbiota-generated metabolites
      play a key role in determining the outcome of infection by bacterial pathogens.
      By consuming and transforming dietary and host-produced metabolites, as well as
      secreting primary and secondary metabolites of their own, the microbiota define
      the chemical environment of the gut and often determine specific host responses.
      Although most gut microbiota-produced metabolites are currently uncharacterized,
      several well-studied molecules made or modified by the microbiota are known to
      affect the growth and virulence of pathogens, including short-chain fatty acids,
      succinate, mucin O-glycans, molecular hydrogen, secondary bile acids, and the AI
      2 quorum sensing autoinducer. We also discuss challenges and possible approaches
      to further study of the chemical interplay between microbiota and
      gastrointestinal pathogens. 

PMID- 25958186
TI  - Artificial photosynthesis.

PMID- 25958187
TI  - Why do high-volume hospitals achieve better outcomes? A systematic review about
      intermediate factors in volume-outcome relationships.
AB  - OBJECTIVE: To assess the role of process and structural factors in volume-outcome
      relationships. DATA SOURCES: Pubmed electronic database, until March 2014. STUDY
      DESIGN: Systematic review. Based on a conceptual framework, peer-reviewed
      publications were included that presented evidence about explanatory factors in
      volume-outcome associations. DATA COLLECTION: Two reviewers extracted information
      about study design, study population, volume and outcome measures, as well as
      explanatory factors. Included publications were appraised for methodological
      quality. PRINCIPAL FINDINGS: After screening 1756 titles, 27 met our inclusion
      criteria. Three main categories of explanatory factors could be identified: 1.
      Compliance to evidence based processes of care (n = 7). 2. Level of
      specialization (n = 11). 3. Hospital level factors (n = 10). In ten studies,
      process and/or structural characteristics partly explained the established volume
      outcome association. The median quality score of the 27 studies was 8 out of a
      possible 18 points. CONCLUSIONS: The vast majority of volume-outcome studies do
      not focus on the underlying mechanism by including process and structural
      characteristics as explanatory factors in their analysis. The methodological
      quality of studies is also modest, which makes us question the available evidence
      for current policies to concentrate care on the basis of volume.

PMID- 25958181
TI  - Mast cell proteases as pharmacological targets.
AB  - Mast cells are rich in proteases, which are the major proteins of intracellular
      granules and are released with histamine and heparin by activated cells. Most of
      these proteases are active in the granule as well as outside of the mast cell
      when secreted, and can cleave targets near degranulating mast cells and in
      adjoining tissue compartments. Some proteases released from mast cells reach the
      bloodstream and may have far-reaching actions. In terms of relative amounts, the
      major mast cell proteases include the tryptases, chymases, cathepsin G,
      carboxypeptidase A3, dipeptidylpeptidase I/cathepsin C, and cathepsins L and S.
      Some mast cells also produce granzyme B, plasminogen activators, and matrix
      metalloproteinases. Tryptases and chymases are almost entirely mast cell
      specific, whereas other proteases, such as cathepsins G, C, and L are expressed
      by a variety of inflammatory cells. Carboxypeptidase A3 expression is a property
      shared by basophils and mast cells. Other proteases, such as mastins, are largely
      basophil-specific, although human basophils are protease-deficient compared with
      their murine counterparts. The major classes of mast cell proteases have been
      targeted for development of therapeutic inhibitors. Also, a human beta-tryptase
      has been proposed as a potential drug itself, to inactivate of snake venins.
      Diseases linked to mast cell proteases include allergic diseases, such as asthma,
      eczema, and anaphylaxis, but also include non-allergic diseases such as
      inflammatory bowel disease, autoimmune arthritis, atherosclerosis, aortic
      aneurysms, hypertension, myocardial infarction, heart failure, pulmonary
      hypertension and scarring diseases of lungs and other organs. In some cases,
      studies performed in mouse models suggest protective or homeostatic roles for
      specific proteases (or groups of proteases) in infections by bacteria, worms and
      other parasites, and even in allergic inflammation. At the same time, a clearer
      picture has emerged of differences in the properties and patterns of expression
      of proteases expressed in human mast cell subsets, and in humans versus other
      mammals. These considerations are influencing prioritization of specific protease
      targets for therapeutic inhibition, as well as options of pre-clinical models,
      disease indications, and choice of topical versus systemic routes of inhibitor
      administration. 

PMID- 25958188
TI  - How to approach breast lesions in children and adolescents.
AB  - Assessment of a pediatric breast lesion always starts with clinical evaluation.
      When imaging of a pediatric breast is indicated, ultrasound is the mainstay. The
      vast majority of pediatric breast complaints are of benign etiology, therefore
      the diagnostic/management approach emphasizes "first do no harm". Correlation
      with age and clinical history helps to direct diagnosis. It is essential to be
      familiar with the imaging appearance of the normal developing breast at various
      Tanner stages, in order to diagnose physiologic breast findings and to minimize
      unnecessary biopsies in young breasts vulnerable to injury. Normal anatomic
      structures, developmental conditions, benign neoplastic and non-neoplastic
      lesions are common causes of breast complaints in children. Uncommon benign
      masses and rarely, secondary more than primary malignancies may present in a
      pediatric breast. Chest wall masses such as Ewing's sarcoma or rhabdomyosarcoma
      occur in children and may involve the breast via contiguous growth or
      locoregional metastasis. In addition, special attention should be given to any
      breast lesion in a child with risk factors predisposing to breast cancer, such as
      known extramammary malignancy, genetic mutations, prior mantle irradiation, or
      strong family history of breast cancer, which usually requires biopsy to exclude
      the possibility of malignancy. CONCLUSION: The developing breast is vulnerable to
      injury, and because breast malignancy is uncommon in children, diagnostic and
      management approach emphasizes "first do no harm". Understanding normal breast
      development and the spectrum of common and uncommon pediatric breast lesions are
      key to the correct diagnosis.

PMID- 25958189
TI  - Simultaneous PET/MR head-neck cancer imaging: Preliminary clinical experience and
      multiparametric evaluation.
AB  - PURPOSE: To evaluate the role of simultaneous hybrid PET/MR imaging and to
      correlate metabolic PET data with morpho-functional parameters derived by MRI in
      patients with head-neck cancer. METHODS: Forty-four patients, with histologically
      confirmed head and neck malignancy (22 primary tumors and 22 follow-up) were
      studied. Patients initially received a clinical exam and endoscopy with direct
      biopsy. Next patients underwent whole body PET/CT followed by PET/MR of the
      head/neck region. PET and MRI studies were separately evaluated by two blinded
      groups (both included one radiologist and one nuclear physician) in order to
      define the presence or absence of lesions/recurrences. Regions of interest (ROIs)
      analysis was conducted on the primary lesion at the level of maximum size on
      metabolic (SUV and MTV), diffusion (ADC) and perfusion (K(trans), Ve, kep and
      iAUC) parameters. RESULTS: PET/MR examinations were successfully performed on all
      44 patients. Agreement between the two blinded groups was found in anatomic
      allocation of lesions by PET/MR (Primary tumors: Cohen's kappa 0.93; FOLLOW-UP:
      Cohen's kappa 0.89). There was a significant correlation between CT-SUV measures
      and MR (e.g., CT-SUV VOI vs. MR-SUV VOI: rho=0.97, p<0.001 for the entire
      sample). There was also significant positive correlations between the ROI area,
      SUV measures, and the metabolic parameters (SUV and MTV) obtained during both
      PET/CT and PET/MR. A significant negative correlation was observed between ADC
      and K(trans) values in the primary tumors. In addition, a significant negative
      correlation existed between MR SUV and ADC in recurrent tumors. CONCLUSION: Our
      study demonstrates the feasibility of PET/MR imaging for primary tumors and
      recurrent tumors evaluations of head/neck malignant lesions. When assessing HNC,
      PET/MR allows simultaneous collection of multiparametric metabolic and functional
      data. This technique therefore allows for a more complete characterization of
      malignant lesions.

PMID- 25958190
TI  - Fingolimod alters inflammatory mediators and vascular permeability in
      intracerebral hemorrhage.
AB  - Intracerebral hemorrhage (ICH) leads to high rates of death and disability. The
      pronounced inflammatory reactions that rapidly follow ICH contribute to disease
      progression. Our recent clinical trial demonstrated that oral administration of
      an immune modulator fingolimod restrained secondary injury derived from initial
      hematoma, but the mechanisms remain unknown. In this study, we aim to investigate
      the effects of fingolimod on inflammatory mediators and vascular permeability in
      the clinical trial of oral fingolimod for intracerebral hemorrhage (ICH). The
      results showed that fingolimod decreased the numbers of circulating CD4(+) T,
      CD8(+) T, CD19(+) B, NK, and NKT cells and they recovered quickly after the drug
      was stopped. The plasma ICAM level was decreased and IL-10 was increased by
      fingolimod. Interestingly, fingolimod protected vascular permeability as
      indicated by a decreased plasma level of MMP9 and the reduced rT1%. In
      conclusion, modulation of systemic inflammation by fingolimod demonstrates that
      it is an effective therapeutic agent for ICH. Fingolimod may prevent
      perihematomal edema enlargement by protecting vascular permeability. 

PMID- 25958192
TI  - A Cost-effectiveness Analysis of Antipsychotics for Treatment of Schizophrenia in
      Uganda.
AB  - BACKGROUND: Reductions in prices following the expiry of patents on second
      generation antipsychotics means that they could be made available to patients
      with schizophrenia in low-income countries. In this study we examine the cost
      effectiveness of antipsychotics for schizophrenia in Uganda. METHODS: We
      developed a decision-analytic 10-state Markov model to represent the clinical and
      treatment course of schizophrenia and the experience of the average patient
      within the Uganda healthcare system. The model was run for a base population of
      25-years-old patients attending Butabika National Referral Mental Hospital, in
      annual cycles over a lifetime horizon. Parameters were derived from a primary
      chart abstraction study, a local community pharmacy survey, published literature,
      and expert opinion where necessary. We computed mean disability-adjusted life
      years (DALYs) and costs (in US$ 2012) for each antipsychotic, incremental cost,
      and DALYs averted as well as incremental cost-effectiveness ratios (ICERs).
      RESULTS: In the base-case analysis, mean DALYs were highest with chlorpromazine
      (27.608), followed by haloperidol (27.563), while olanzapine (27.552) and
      risperidone had the lowest DALYs (27.557). Expected costs were highest with
      quetiapine (US$4943), and lowest with risperidone (US$4424). Compared to
      chlorpromazine, haloperidol was a dominant option (i.e. it was less costly and
      more effective); and risperidone was dominant over both haloperidol and
      quetiapine. The ICER comparing olanzapine to risperidone was US$5868 per DALY
      averted. CONCLUSION: When choosing between first-generation antipsychotics,
      clinicians should consider haloperidol as the first-line agent for schizophrenia.
      However, overall, risperidone is a cost-saving strategy; policymakers should
      consider its addition to essential medicines lists for treatment of schizophrenia
      in Uganda.

PMID- 25958191
TI  - Health Economic Evaluation of a Strict Glucose Control Guideline Implemented
      Using Point-of-Care Testing in Three Intensive Care Units in The Netherlands.
AB  - BACKGROUND: Point-of-care testing of blood glucose (BG-POCT) is essential for
      safe and effective insulin titrations in critically ill patients under glucose
      control with insulin. The costs associated with this practice are considered
      substantial, especially when more frequent blood glucose (BG) testing is needed,
      as with more strict glucose control (SGC) aiming for lower BG levels. OBJECTIVE:
      The objective of this study was to estimate, from a hospital perspective, the
      incremental cost effectiveness of an SGC guideline, aiming for BG levels of 4.4
      6.1 mmol/L, compared to the situation before implementation of that guideline
      (aiming for BG levels <8.3 mmol/L), both using BG-POCT. METHODS: This is a
      secondary analysis of a guideline implementation project aiming for
      implementation of a guideline of SGC in three intensive care units in The
      Netherlands. A Markov model including the four health states 'target glucose',
      'hyperglycaemia' (defined as BG levels >6.1 mmol/L), 'hypoglycaemia' (defined as
      BG levels <4.4 mmol/L) and 'in-hospital death' was developed to compare expected
      costs, number of patients within target and number of life-years saved before and
      after implementation of the SGC guideline. The effectiveness estimates are based
      on empirical data from 3195 patients 12 and 24 months before and after
      implementation of the guideline, respectively. All costs have been converted to
      price year 2013, and are estimated based on hospital data, the literature and
      available price lists. RESULTS: The number of BG-POCT increased from 4.8
      [interquartile range (IQR) 2.6-6.7] to 8.0 [IQR 4.1-11.2] per patient per day,
      accruing 58% higher costs for BG-POCT (?13.56 vs. ?8.57 per patient) in the SGC
      protocol versus the situation before implementation. When taking total hospital
      costs and clinical effects into account, implementation of the SGC guideline
      increased total hospital costs per patient by 1.8%, i.e., ?355 (from ?20,617 to
      ?20,972) during the inpatient stay, while the number of patients in target
      glucose levels increased by 1.4% (i.e., from 881 to 895 per 1000 patients). This
      translates to an incremental cost-effectiveness ratio of ?25 per additional
      patient within the target glucose level. The model outcomes are most sensitive to
      changes in ICU length of stay. CONCLUSION: The increase in the number of patients
      and time within target glucose levels is achieved with a small increase in total
      direct hospital costs.

PMID- 25958193
TI  - Trends and outcomes in allogeneic hematopoietic stem cell transplant for multiple
      myeloma at Mayo Clinic.
AB  - BACKGROUND: Allogeneic transplant in myeloma remains controversial. PATIENTS AND
      METHODS: We performed a retrospective review of 76 patients in the Mayo Clinic
      database from 1993 to 2013 who underwent allogeneic hematopoietic stem cell
      transplant (HSCT) for myeloma. RESULTS: After excluding ineligible patients,
      among the remaining 66 patients, median age at transplant was 42 years and 87%
      had residual disease at the time of transplant. Myeloablative (71%) versus
      reduced intensity conditioning (29%), matched sibling donors (70%) versus
      unrelated donors showed no outcome difference. Median overall survival from the
      time of diagnosis and transplant were 75 and 24 months, respectively. Median time
      to disease progression (TTP) was 15 months and treatment-related mortality was
      20% at day 100. Acute and chronic graft versus host disease (cGVHD) developed in
      61% and 48% patients, respectively. In univariate analysis of overall survival
      (OS), factors predicting adverse outcome were pretransplant 24-hour total urinary
      protein (P = .035), peripheral blood versus bone marrow (OS 18 vs. 41 months; P =
      .02), number of previous therapies (P = .014), time from autologous to allogeneic
      HSCT (P = .019), and cGVHD (P = .01). TTP was adversely affected by number of
      previous regimens (P = .036) and PB as graft source (P = .016). In multivariate
      analysis for progression-free survival, number of previous regimens (P = .04),
      and for OS, time between autologous and allogeneic HSCT was significant (P =
      .009). CONCLUSION: In 162 matched control subjects who were human leukocytoe
      antigen-typed, there were no survivors at 12 years compared with 20% in the group
      who received a transplant. In a second control group with 197 second autologous
      transplants, 10-year OS was 8%.

PMID- 25958194
TI  - Disparity in rehabilitation: another inconvenient truth.

PMID- 25958195
TI  - Sparse Non-negative Matrix Factorization (SNMF) based color unmixing for breast
      histopathological image analysis.
AB  - Color deconvolution has emerged as a popular method for color unmixing as a pre
      processing step for image analysis of digital pathology images. One deficiency of
      this approach is that the stain matrix is pre-defined which requires specific
      knowledge of the data. This paper presents an unsupervised Sparse Non-negative
      Matrix Factorization (SNMF) based approach for color unmixing. We evaluate this
      approach for color unmixing of breast pathology images. Compared to Non-negative
      Matrix Factorization (NMF), the sparseness constraint imposed on coefficient
      matrix aims to use more meaningful representation of color components for
      separating stained colors. In this work SNMF is leveraged for decomposing pure
      stained color in both Immunohistochemistry (IHC) and Hematoxylin and Eosin (H&E)
      images. SNMF is compared with Principle Component Analysis (PCA), Independent
      Component Analysis (ICA), Color Deconvolution (CD), and Non-negative Matrix
      Factorization (NMF) based approaches. SNMF demonstrated improved performance in
      decomposing brown diaminobenzidine (DAB) component from 36 IHC images as well as
      accurately segmenting about 1400 nuclei and 500 lymphocytes from H & E images.

PMID- 25958196
TI  - Illness beliefs and the sociocultural context of diabetes self-management in
      British South Asians: a mixed methods study.
AB  - BACKGROUND: British South Asians have a higher incidence of diabetes and poorer
      health outcomes compared to the general UK population. Beliefs about diabetes are
      known to play an important role in self-management, yet little is known about the
      sociocultural context in shaping beliefs. This study aimed to explore the
      influence of sociocultural context on illness beliefs and diabetes self
      management in British South Asians. METHODS: A mixed methods approach was used.
      67 participants recruited using random and purposive sampling, completed a
      questionnaire measuring illness beliefs, fatalism, health outcomes and
      demographics; 37 participants completed a social network survey interview and
      semi-structured interviews. Results were analysed using SPSS and thematic
      analysis. RESULTS: Quantitative data found certain social network characteristics
      (emotional and illness work) were related to perceived concern, emotional
      distress and health outcomes (p < 0.05). After multivariate analysis, emotional
      work remained a significant predictor of perceived concern and emotional distress
      related to diabetes (p < 0.05). Analysis of the qualitative data suggest that
      fatalistic attitudes and beliefs influences self-management practices and
      alternative food 'therapies' are used which are often recommended by social
      networks. CONCLUSIONS: Diabetes-related illness beliefs and self-management
      appear to be shaped by the sociocultural context. Better understanding of the
      contextual determinants of behaviour could facilitate the development of
      culturally appropriate interventions to modify beliefs and support self
      management in this population.

PMID- 25958197
TI  - Experimental vertical transmission of Rickettsia parkeri in the Gulf Coast tick,
      Amblyomma maculatum.
AB  - Rickettsia parkeri, an obligate intracellular bacterium, is a member of the
      spotted fever group of rickettsiae (SFGR), and is transmitted to humans and other
      animals by invertebrate vectors. In the United States, the primary vector of R.
      parkeri is the Gulf Coast tick, Amblyomma maculatum Koch. This study investigates
      the vertical transmission dynamics of R. parkeri within a field-derived,
      naturally infected colony of A. maculatum. Transovarial and transstadial
      transmission of the pathogen was observed over three generations, with
      transovarial transmission efficiency averaging 83.7% and transstadial
      transmission rates approaching 100%. Fitness costs were determined by comparing
      reproduction values of the R. parkeri-infected A. maculatum colony to values from
      a R. parkeri-free colony. No significant reproductive fitness costs to the host
      ticks were detected in the R. parkeri-infected A. maculatum colony. Significantly
      fewer engorged F1 nymphs and F2 larvae of the R. parkeri-free colony succeeded in
      molting, suggesting that there may be some advantage to survival conferred by R.
      parkeri. The results of this study indicate that R. parkeri is maintained in A.
      maculatum populations efficiently by transovarial and transstadial transmission
      without any noticeable effects on tick reproduction or survival. 

PMID- 25958198
TI  - RNA-Seq versus oligonucleotide array assessment of dose-dependent TCDD-elicited
      hepatic gene expression in mice.
AB  - BACKGROUND: Dose-dependent differential gene expression provides critical
      information required for regulatory decision-making. The lower costs associated
      with RNA-Seq have made it the preferred technology for transcriptomic analysis.
      However, concordance between RNA-Seq and microarray analyses in dose response
      studies has not been adequately vetted. RESULTS: We compared the hepatic
      transcriptome of C57BL/6 mice following gavage with sesame oil vehicle, 0.01,
      0.03, 0.1, 0.3, 1, 3, 10, or 30 MUg/kg TCDD every 4 days for 28 days using
      Illumina HiSeq RNA-Sequencing (RNA-Seq) and Agilent 4 * 44 K microarrays using
      the same normalization and analysis approach. RNA-Seq and microarray analysis
      identified a total of 18,063 and 16,403 genes, respectively, that were expressed
      in the liver. RNA-Seq analysis for differentially expressed genes (DEGs) varied
      dramatically depending on the P1(t) cut-off while microarray results varied more
      based on the fold change criteria, although responses strongly correlated.
      Verification by WaferGen SmartChip QRTPCR revealed that RNA-Seq had a false
      discovery rate of 24% compared to 54% for microarray analysis. Dose-response
      modeling of RNA-Seq and microarray data demonstrated similar point of departure
      (POD) and ED50 estimates for common DEGs. CONCLUSIONS: There was a strong
      correspondence between RNA-Seq and Agilent array transcriptome profiling when
      using the same samples and analysis strategy. However, RNA-Seq provided superior
      quantitative data, identifying more genes and DEGs, as well as qualitative
      information regarding identity and annotation for dose response modeling in
      support of regulatory decision-making.

PMID- 25958199
TI  - Mitogen- and stress-activated Kinase 1 mediates Epstein-Barr virus latent
      membrane protein 1-promoted cell transformation in nasopharyngeal carcinoma
      through its induction of Fra-1 and c-Jun genes.
AB  - BACKGROUND: Mitogen- and Stress-Activated Kinase 1 (MSK1) is a nuclear kinase
      that serves as active link between extracellular signals and the primary response
      of gene expression. However, the involvement of MSK1 in malignant transformation
      and cancer development is not well understood. In this study, we aimed to explore
      the role of MSK1 in Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1)
      promoted carcinogenesis of nasopharyngeal carcinoma (NPC). METHODS: The level of
      MSK1 phosphorylation at Thr581 was detected by the immunohistochemical analysis
      in NPC tissues and normal nasopharynx tissues, and its correlation with LMP1 was
      analyzed in NPC tissues and cell lines. Using MSK1 inhibitor H89 or small
      interfering RNA (siRNA)-MSK1, the effects of MSK1 on LMP1-promoted CNE1 cell
      proliferation and transformation were evaluated by CCK-8 assay, flow cytometry
      and focus-forming assay respectively. Furthermore, the regulatory role of MSK1
      mediated histone H3 phosphorylation at Ser10 on the promoter activity and
      expression of Fra-1 or c-Jun was determined by reporter gene assay and western
      blotting analysis. RESULTS: Immunohistochemical analysis revealed that the level
      of MSK1 phosphorylation at Thr581 was significantly higher in the poorly
      differentiated NPC tissues than that in normal nasopharynx tissues (P < 0.001).
      Moreover, high level of phosphorylated MSK1 was positively correlated with the
      expression of LMP1 in NPC tissues (r = 0.393, P = 0.002) and cell lines. MSK1
      inhibitor H89 or knockdown of MSK1 by siRNA dramatically suppressed LMP1-promoted
      CNE1 cell proliferation, which was associated with the induction of cell cycle
      arrest at G0/G1 phase. In addition, the anchorage-independent growth promoted by
      LMP1 was blocked in MSK1 knockdown cells. When the activity or expression of MSK1
      was inhibited, LMP1-induced promoter activities of Fra-1 and c-Jun as well as
      their protein levels were greatly reduced. It was found that only H3 WT, but not
      mutant H3 S10A, dramatically increased LMP1 induction of Fra-1 and c-Jun genes
      compared with mock cells. CONCLUSION: Increased MSK1 activity is critically
      important for LMP1-promoted cell proliferation and transformation in NPC, which
      may be correlated with its induction of Fra-1 and c-Jun through phosphorylation
      of histone H3 at Ser10.

PMID- 25958201
TI  - Global in vitro activity of tigecycline and comparator agents: Tigecycline
      Evaluation and Surveillance Trial 2004-2013.
AB  - BACKGROUND: The Tigecycline Evaluation and Surveillance Trial (TEST) is a global
      antimicrobial susceptibility surveillance study which has been ongoing since
      2004. This report examines the in vitro activity of tigecycline and comparators
      against clinically important pathogens collected globally between 2004 and 2013.
      METHODS: Antimicrobial susceptibility was determined using guidelines published
      by the Clinical and Laboratory Standards Institute. The Cochran Armitage Trend
      Test was used to identify statistically significant changes in susceptibility
      between 2004 and 2013. RESULTS: Among the Enterobacteriaceae susceptibility was
      highest to the carbapenems [imipenem 97.1% (24,655/25,381), meropenem 97.0%
      (90,714/93,518)], tigecycline (97.0%, 115,361/118,899) and amikacin (96.9%,
      115,200/118,899). Against Acinetobacter baumannii the highest rates of
      susceptibility were for minocycline (84.5%, 14,178/16,778) and imipenem (80.0%,
      3,037/3,795). The MIC90 for tigecycline was 2 mg/L. 40% (6,743/16,778) of A.
      baumannii isolates were multidrug-resistant. Enterococci were highly susceptible
      to tigecycline and linezolid (>99%); vancomycin resistance was observed among 2%
      of Enterococcus faecalis (325/14,615) and 35% of Enterococcus faecium
      (2,136/6,167) globally. 40% (14,647/36,448) of Staphylococcus aureus were
      methicillin-resistant while 15% (2,152/14,562) of Streptococcus pneumoniae were
      penicillin-resistant. Against S. aureus and S. pneumoniae susceptibility to
      linezolid, vancomycin, and tigecycline was >=99.9%. Globally, 81% (331/410) of
      statistically significant susceptibility changes during the study period were
      decreases in susceptibility. CONCLUSIONS: Amikacin, the carbapenems, and
      tigecycline were active against most gram-negative pathogens while linezolid,
      tigecycline, and vancomycin retained activity against most gram-positive
      pathogens collected in TEST during 2004-2013.

PMID- 25958202
TI  - microRNA network analysis identifies miR-29 cluster as key regulator of LAMA2 in
      ependymoma.

PMID- 25958200
TI  - Strategies to uncover undiagnosed HIV infection among heterosexuals at high risk
      and link them to HIV care with high retention: a "seek, test, treat, and retain"
      study.
AB  - BACKGROUND: Over 50,000 individuals become infected with HIV annually in the
      U.S., and over a quarter of HIV infected individuals are heterosexuals.
      Undiagnosed HIV infection, as well as a lack of retention in care among those
      diagnosed, are both primary factors contributing to ongoing HIV incidence.
      Further, there are racial/ethnic disparities in undiagnosed HIV and engagement in
      care, with African Americans/Blacks and Latinos remaining undiagnosed longer and
      less engaged in care than Whites, signaling the need for culturally targeted
      intervention approaches to seek and test those with undiagnosed HIV infection,
      and link them to care with high retention. METHODS/DESIGN: The study has two
      components: one to seek out and test heterosexuals at high risk for HIV
      infection, and another to link those found infected to HIV care with high
      retention. We will recruit sexually active African American/Black and Latino
      adults who have opposite sex partners, negative or unknown HIV status, and reside
      in locations with high poverty and HIV prevalence. The "Seek and Test" component
      will compare the efficacy and cost effectiveness of two strategies to uncover
      undiagnosed HIV infection: venue-based sampling and respondent-driven sampling
      (RDS). Among those recruited by RDS and found to have HIV infection, a "Treat and
      Retain" component will assess the efficacy of a peer-driven intervention compared
      to a control arm with respect to time to an HIV care appointment and health
      indicators using a cluster randomized controlled trial design to minimize
      contamination. RDS initial seeds will be randomly assigned to the intervention or
      control arm at a 1:1 ratio and all recruits will be assigned to the same arm as
      the recruiter. Participants will be followed for 12 months with outcomes assessed
      using medical records and biomarkers, such as HIV viral load. DISCUSSION:
      Heterosexuals do not test for HIV as frequently as and are diagnosed later than
      other risk groups. The study has the potential to contribute an efficient,
      innovative, and sustainable multi-level recruitment approach and intervention to
      the HIV prevention portfolio. Because the majority of heterosexuals at high risk
      are African American/Black or Latino, the study has great potential to reduce
      racial/ethnic disparities in HIV/AIDS. TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT01607541, Registered May 23, 2012.

PMID- 25958203
TI  - A scoping review of the proximal humerus fracture literature.
AB  - BACKGROUND: Proximal humerus fractures are a common fragility fracture that
      significantly affects the independence of older adults. The outcomes of these
      fractures are frequently disappointing and previous systematic reviews are unable
      to guide clinical practice. Through an integrated knowledge user collaboration,
      we sought to map the breadth of literature available to guide the management of
      proximal humerus fractures. METHODS: We utilized a scoping review technique
      because of its novel ability to map research activity and identify knowledge gaps
      in fields with diverse treatments. Through multiple electronic database searches,
      we identified a comprehensive body of proximal humerus fracture literature that
      was classified into eight research themes. Meta-data from each study were
      abstracted and descriptive statistics were used to summarize the results.
      RESULTS: 1,051 studies met our inclusion criteria with the majority of research
      being performed in Europe (64%). The included literature consists primarily of
      surgical treatment studies (67%) and biomechanical fracture models (10%). Nearly
      half of all clinical studies are uncontrolled case series of a single treatment
      (48%). Non-randomized comparative studies represented 12% of the literature and
      only 3% of the studies were randomized controlled trials. Finally, studies with a
      primary outcome examining the effectiveness of non-operative treatment or using a
      prognostic study design were also uncommon (4% and 6%, respectively).
      CONCLUSIONS: The current study provides a comprehensive summary of the existing
      proximal humerus fracture literature using a thematic framework developed by a
      multi-disciplinary collaboration. Several knowledge gaps have been identified and
      have generated a roadmap for future research priorities.

PMID- 25958204
TI  - Buforin IIb induces endoplasmic reticulum stress-mediated apoptosis in HeLa
      cells.
AB  - Buforin IIb, a novel cell-penetrating anticancer peptide derived from histone
      H2A, has been reported to induce mitochondria-dependent apoptosis in tumor cells.
      However, increasing evidence suggests that endoplasmic reticulum and mitochondria
      cooperate to signal cell death. In this study, we investigated the mechanism of
      buforin IIb-induced apoptosis in human cervical carcinoma HeLa cells by focusing
      on ER stress-mediated mitochondrial membrane permeabilization. Two-dimensional
      PAGE coupled with MALDI-TOF and western blot analysis showed that buforin IIb
      treatment of HeLa cells resulted in upregulation of ER stress proteins. PBA (ER
      stress inhibitor) and BAPTA/AM (Ca(2+) chelator) pretreatment rescued viability
      of buforin IIb-treated cells through abolishing phosphorylation of SAPK/JNK and
      p38 MAPK. SP600125 (SAPK/JNK inhibitor) and SB203580 (p38 MAPK inhibitor)
      attenuated down-regulation of Bcl-xL/Bcl-2, mitochondrial translocation of Bax,
      and cytochrome c release from mitochondria. Taken together, our data suggest that
      the ER stress pathway has an important role in the buforin IIb-induced apoptosis
      in HeLa cells. 

PMID- 25958206
TI  - Identification of autoreactive CD8+ T cell responses targeting chromogranin A in
      humanized NOD mice and type 1 diabetes patients.
AB  - ChgA has recently been identified as the autoantigen for diabetogenic CD4(+) T
      cells in NOD mice and T1D patients. However, autoreactive CD8(+) T-cell responses
      targeting ChgA haven't been studied yet. Here several HLA-A*0201-restricted
      peptides derived from mChgA and hChgA were selected by an integrated
      computational prediction approach, followed by an HLA-A*0201 binding assay.
      MChgA10-19 and mChgA(43-52) peptides, which bound well with HLA-A*0201 molecule,
      induced significant proliferation and IFN-gamma-releasing of splenocytes from
      diabetic NOD.beta2m(null).HHD mice. Notably, flow cytometry analysis found that
      mChgA(10-19) and mChgA(43-52) stimulated the production of IFN-gamma, perforin,
      and IL-17 by splenic CD8(+) T cells of diabetic NOD.beta2m(null).HHD mice.
      Furthermore, hChgA(10-19) and hChgA(43-52)-induced IFN-gamma releasing by
      specific CD8(+) T cells were frequently detected in recent-onset HLA-A*0201
      positive T1D patients. Thus, this study demonstrated that autoreactive CD8(+) T
      cells targeting ChgA were present in NOD.beta2m(null).HHD mice and T1D patients,
      and might contribute to pathogenesis of T1D through secreting proinflammatory
      cytokines and cytotoxic molecules.

PMID- 25958205
TI  - Epigenetic mechanisms in schizophrenia.
AB  - Epigenetic modifications, including DNA methylation, histone modifications, and
      non-coding RNAs, have been implicated in a number of complex diseases.
      Schizophrenia and other major psychiatric and neurodevelopmental disorders are
      associated with abnormalities in multiple epigenetic mechanisms, resulting in
      altered gene expression during development and adulthood. Polymorphisms and copy
      number variants in schizophrenia risk genes contribute to the high heritability
      of the disease, but environmental factors that lead to epigenetic modifications
      may either reduce or exacerbate the expression of molecular and behavioral
      phenotypes associated with schizophrenia and related disorders. In the present
      paper, we will review the current understanding of molecular dysregulation in
      schizophrenia, including disruption of the dopamine, NMDA, and GABA signaling
      pathways, and discuss the role of epigenetic factors underlying disease
      pathology. 

PMID- 25958208
TI  - Reverse shoulder arthroplasty versus hemiarthroplasty for treatment of proximal
      humerus fractures.
AB  - BACKGROUND: Whereas most proximal humerus fractures are treated nonoperatively,
      complex 3- and 4-part fractures may require shoulder arthroplasty. Hemi-shoulder
      arthroplasty (HSA) has been the standard treatment, but recently there has been
      discussion and utilization of reverse total shoulder arthroplasty (RTSA) as a
      viable treatment option. This study evaluated the national utilization of RTSA
      and HSA for proximal humerus fractures and compared patient and hospital
      characteristics associated with each procedure. METHODS: This study used the
      Nationwide Inpatient Sample database for 2011, which allows national estimates of
      inpatient hospital discharges. Patients were selected by diagnosis and procedure
      codes to identify those who underwent RTSA or HSA for treatment of proximal
      humerus fractures. Patient and hospital characteristics associated with each
      procedure as well as in-hospital complication rates were identified. RESULTS: An
      estimated 7714 patients with proximal humerus fractures were selected, 27.4% of
      whom were treated with RTSA. Except for increased age, patient characteristics
      were similar between groups, as were complication rates. RTSA was more likely to
      be performed over HSA in small, rural, nonteaching hospitals and also in those
      that had already adopted and performed a high volume of RTSA procedures for other
      diagnoses. CONCLUSIONS: Although HSA remains the most common arthroplasty choice
      for proximal humerus fractures, RTSA is becoming widely used. Patient
      characteristics and complications were similar between the 2 procedures, and as
      clinical evidence appears to show improved outcomes with RTSA, it is likely that
      acceptance of RTSA will continue to grow.

PMID- 25958207
TI  - Targeting the isoprenoid pathway to abrogate progression of pulmonary fibrosis.
AB  - Fibrotic remodeling in lung injury is a major cause of morbidity. The mechanism
      that mediates the ongoing fibrosis is unclear, and there is no available
      treatment to abate the aberrant repair. Reactive oxygen species (ROS) have a
      critical role in inducing fibrosis by modulating extracellular matrix deposition.
      Specifically, mitochondrial hydrogen peroxide (H2O2) production by alveolar
      macrophages is directly linked to pulmonary fibrosis as inhibition of
      mitochondrial H2O2 attenuates the fibrotic response in mice. Prior studies
      indicate that the small GTP-binding protein, Rac1, directly mediates H2O2
      generation in the mitochondrial intermembrane space. Geranylgeranylation of the C
      terminal cysteine residue (Cys(189)) is required for Rac1 activation and
      mitochondrial import. We hypothesized that impairment of geranylgeranylation
      would limit mitochondrial oxidative stress and, thus, abrogate progression of
      pulmonary fibrosis. By targeting the isoprenoid pathway with a novel agent,
      digeranyl bisphosphonate (DGBP), which impairs geranylgeranylation, we
      demonstrate that Rac1 mitochondrial import, mitochondrial oxidative stress, and
      progression of the fibrotic response to lung injury are significantly attenuated.
      These observations reveal that targeting the isoprenoid pathway to alter Rac1
      geranylgeranylation halts the progression of pulmonary fibrosis after lung
      injury. 

PMID- 25958209
TI  - The incidence of radiographic aseptic loosening of the humeral component in
      reverse total shoulder arthroplasty.
AB  - BACKGROUND: The reverse total shoulder arthroplasty (RTSA) has been used in the
      treatment of complex shoulder problems. The incidence of aseptic loosening of the
      humeral component has not been previously reported. METHODS: This is a
      multicenter, retrospective, blinded, case-control radiographic review of 292
      patients to determine the rate of humeral stem loosening. There were 177 cemented
      and 115 press-fit humeral components. Radiographs were critiqued for radiolucent
      lines adjacent to the humeral stem based on the method described by Gruen et al.
      RESULTS: The overall rate of loosening was 0.74%. No radiographic loosening
      occurred in the press-fit group (115 stems). In the cemented group (177 stems), 2
      shoulders (1.18%) were identified with radiographically loose stems. No loosening
      occurred in the press-fit group. No statistically significant difference was
      found in humeral stem loosening when the press-fit group and the cemented group
      were compared (P = .198). DISCUSSION: Our study indicates the cemented or press
      fit RTSA system will result in a low incidence of radiolucent lines and
      radiographic loosening. Compared with historical survivorship of conventional
      anatomic total shoulder arthroplasty, RTSA shows a lower rate of radiographic
      stem loosening at a mean of 38.46 months. CONCLUSIONS: The RTSA has a low
      incidence of humeral stem loosening at midterm. These results underscore the
      importance of careful selection of patients to provide the benefits of this
      surgical technique. Press-fit fixation may provide a lower risk to stem
      loosening.

PMID- 25958210
TI  - Coronal plane radiographic evaluation of the single TightRope technique in the
      treatment of acute acromioclavicular joint injury.
AB  - BACKGROUND: This study aimed to demonstrate the technical aspects of the single
      TightRope (Arthrex, Naples, FL, USA) procedure for acute acromioclavicular
      coracoclavicular joint dislocation, identify the predictive factors influencing
      its outcome, and assess and validate the significance of specific radiologic
      parameters. METHODS: We reviewed true anteroposterior shoulder radiographs of 62
      consecutive patients who had undergone surgical reconstruction using TightRope
      for an acute acromioclavicular-coracoclavicular injury. All patients were
      followed up for at least 12 months between October 2009 and March 2012 and were
      divided into dissociated or nondissociated groups according to their surgical
      outcome. We measured the clavicle tunnel anteroposterior angle, distal clavicular
      tunnel placement, and tunnel-to-medial coracoid ratio, and compared the
      parameters in each group after a satisfactory intraclass correlation coefficient
      reliability test result. RESULTS: The angles of patients in the dissociated group
      were more acute compared with the angles of those in the nondissociated group,
      which were perpendicular, as verified statistically using the paired t test. The
      difference in the distal clavicular tunnel placement and tunnel-to-medial
      coracoid ratio between the groups was not significant. Therefore, tunnel
      placement is not influenced by coracoclavicular dissociation. CONCLUSIONS: The
      clavicle tunnel anteroposterior angle can be used as a predictor of surgical
      outcome in coracoclavicular augmentation surgery. The surgeon should strive to
      place a perpendicular hole from the clavicle to the coracoid process for the
      TightRope fixation to enable a successful reconstruction of the acute
      acromioclavicular-coracoclavicular injury.

PMID- 25958211
TI  - Quality of research and quality of reporting in elbow surgery trials.
AB  - BACKGROUND: Randomized controlled trials (RCTs) are high in the hierarchy of
      scientific evidence, but possible sources of bias should be identified or even
      excluded. This systematic review assessed the methodologic quality and the
      quality of reporting of the RCTs on the treatment of elbow pathology. METHODS: A
      systematic review of RCTs was performed on the treatment of elbow pathology.
      PubMed/MEDLINE, Embase, and the Cochrane Library were searched for relevant
      trials. Thirty-five of the initial 540 articles being an (pseudo) RCT on invasive
      treatment of elbow pathology in humans were included. These were scored with the
      use of an adapted Checklists to Evaluate A Report of a Nonpharmacologic Trial
      (CLEAR-NPT). To assess quality of reporting, points were administered to the
      articles based on the results from CLEAR-NPT list. The highest possible score for
      quality is 26 points. RESULTS: The average quality score was 18.1 points (range,
      10-25 points). The mean scores were 19.5 for trials published in the American
      Journal of Sports Medicine, 19.8 for those published in the Journal of Bone and
      Joint Surgery, and 20.3 for those published in the Journal of Shoulder and Elbow
      Surgery. CONCLUSIONS: The most important finding was that the overall quality and
      the quality of reporting has not improved over the years and that the overall
      quality of the selected studies and the quality of reporting in these trials is
      not related to the journal they are published in.

PMID- 25958212
TI  - Shoulder linked arthroplasty in patients with obstetric brachial plexus palsy can
      improve quality of life and function at short-term follow-up.
AB  - BACKGROUND: Patients with obstetric brachial plexus palsy (OBPP) are prone to
      develop degenerative shoulder disease at a younger age than the general
      population. To date, no reports have been published on the complexities or
      outcome of shoulder arthroplasty (SA) in this unique patient group. METHODS: We
      reviewed of 9 SAs in 9 patients (3 men and 6 women) with OBPP with mean follow-up
      5.1 years (range, 2.6-7.6 years). Patients were a mean age of 29 years (range, 16
      56 years). Patients had undergone a mean of 3 previous operations (range, 2-6).
      All patients underwent linked constrained SA. RESULTS: The mean Oxford Shoulder
      Score increased from 8 (range, 3-10) preoperatively to 21 (range, 12-32) at the
      final follow-up (P < .001) predominantly due to pain relief. Mean range of active
      forward elevation and abduction improved from 35 degrees  and 39 degrees  to 46
      degrees  and 45 degrees , respectively. Patients improved significantly in 2 of 8
      Short-Form 36-Item health-related quality of life domains, bodily pain (P = .013)
      and mental health (P = .035), and the overall physical component summary score (P
      = .006). Range of motion had mild improvements. Three required reoperation (33%),
      comprising 1 excision of heterotopic ossification, 1 trimming of a prominent
      screw, and 1 deltoid rupture repair. CONCLUSIONS: SA is effective at relieving
      pain and health-related quality of life for young patients with OBPP; however,
      compared with the general population, the complication rate is high and
      functional gains are small.

PMID- 25958213
TI  - T2* mapping and delayed gadolinium-enhanced magnetic resonance imaging in
      cartilage (dGEMRIC) of humeral articular cartilage--a histologically controlled
      study.
AB  - BACKGROUND: Cartilage biochemical imaging modalities that include the magnetic
      resonance imaging (MRI) techniques of T2* mapping (sensitive to water content and
      collagen fiber network) and delayed gadolinium-enhanced MRI of cartilage
      (dGEMRIC, sensitive to the glycosaminoglycan content) can be effective
      instruments for early diagnosis and reliable follow-up of cartilage damage. The
      purpose of this study was to provide T2* mapping and dGEMRIC values in various
      histologic grades of cartilage degeneration in humeral articular cartilage.
      METHODS: A histologically controlled in vitro study was conducted that included
      human humeral head cartilage specimens with various histologic grades of
      cartilage degeneration. High-resolution, 3-dimensional (3D) T2* mapping and
      dGEMRIC were performed that enabled the correlation of MRI and histology data.
      Cartilage degeneration was graded according to the Mankin score, which evaluates
      surface morphology, cellularity, toluidine blue staining, and tidemark integrity.
      SPSS software was used for statistical analyses. RESULTS: Both MRI mapping values
      decreased significantly (P < .001) with increasing cartilage degeneration.
      Spearman rank analysis revealed a significant correlation (correlation
      coefficients ranging from -0.315 to 0.784; P < .001) between the various
      histologic parameters and the T2* and T1Gd mapping values. CONCLUSION: This study
      demonstrates the feasibility of 3D T2* and dGEMRIC to identify various histologic
      grades of cartilage damage of humeral articular cartilage. With regard to the
      advantages of these mapping techniques with high image resolution and the ability
      to accomplish a 3D biochemically sensitive imaging, we consider that these
      imaging techniques can make a positive contribution to the currently evolving
      science and practice of cartilage biochemical imaging.

PMID- 25958214
TI  - Outcomes of reverse total shoulder arthroplasty in a senior athletic population.
AB  - BACKGROUND: This study evaluated the clinical and radiographic outcomes of
      reverse total shoulder arthroplasty (RTSA) in a senior athletic population
      playing both low- and high-impact sports. MATERIALS AND METHODS: We evaluated 41
      RTSAs performed in 40 patients who continued to play both low- and high-impact
      sports after surgery. The mean age was 73 years, and the mean follow-up period
      was 43 months, with a minimum of 35 months. Clinical and radiographic outcomes
      were examined. RESULTS: Ninety-five percent of patients indicated that they were
      able to return to sports at the same level as before surgery or at a higher
      level, and only 13% reported increased pain after playing their sport after
      undergoing an RTSA. The median American Shoulder and Elbow Surgeons score
      improved from 31 preoperatively to 72 postoperatively (P < .001). The median
      Constant score improved from 25 preoperatively to 83 postoperatively (P < .001).
      The median Subjective Shoulder Value improved from 27% preoperatively to 90%
      postoperatively (P < .001), and the median visual analog scale score improved
      from 7.2 preoperatively to 1.1 postoperatively (P < .001). The overall
      complication rate was 7%. One zone of lucency was noted in 17% of humeral stems,
      with 1 case of early subsidence but no cases with loosening at final follow-up.
      The glenoid notching rate was 7%, with no cases of glenoid subsidence, lucency,
      or loosening. CONCLUSION: RTSA in senior athletes can be safely performed with
      good clinical results. No prominent mode of mechanical or clinical failure has
      been identified with short-term follow-up.

PMID- 25958215
TI  - Osteochondral autograft plug transfer for treatment of osteochondritis dissecans
      of the capitellum in adolescent athletes.
AB  - BACKGROUND: Osteochondritis dissecans (OCD) of the capitellum is a condition most
      commonly seen in adolescents involved in repetitive overhead sports and can
      profoundly affect ability to return to play and long-term elbow function.
      Treatment of large, unstable defects in the elbow with osteochondral autograft
      plug transfer has not been adequately studied. METHODS: We retrospectively
      identified 11 teenaged patients with large (>1 cm(2)) capitellar OCD treated with
      osteochondral autograft plug transfer. Average age at the time of surgery was
      14.5 years (range, 13-17 years). Outcome measures obtained included return to
      play, preoperative and postoperative elbow range of motion, Disabilities of Arm,
      Shoulder and Hand (DASH; Institute for Work and Health, Toronto, ON, Canada) by
      telephone interview, and osseous integration on radiographs. All 11 patients were
      available for evaluation at an average of 22.7 months (range, 6-49 months)
      postoperatively. RESULTS: All patients were involved in competitive high school
      athletics and returned to at least their preinjury level of play. Average return
      to play was 4.4 months (range 3-7 months). The average final DASH was 1.4 (95%
      confidence interval, 0.6-2.1), and the average final sport-specific DASH was 1.7
      (95% confidence interval -1.8 to 5.2). Elbow range of motion significantly
      improved, including improvement in flexion from a preoperative average of 126
      degrees  to a postoperative average of 141 degrees  (P = .009) and improvement in
      extension from a preoperative average of 21 degrees  to a postoperative average
      of 5 degrees  (P = .006). CONCLUSIONS: Treatment of large, unstable OCD lesions
      of the capitellum in adolescent athletes allows reliable return to play, is safe,
      and has good clinical outcomes at short-term follow-up.

PMID- 25958217
TI  - Glenoid version and inclination are risk factors for anterior shoulder
      dislocation.
AB  - HYPOTHESIS: Although the contribution of the capsuloligamentous structures and
      dynamic muscle balance to shoulder stability has been well documented, the role
      of the osseous anatomy of the glenoid has not been thoroughly evaluated. This
      study investigated glenoid version and inclination in patients with a documented
      anterior shoulder dislocation and compared it with a control group. We
      hypothesized that patients with a prior anterior dislocation would have more
      anterior version and increased inferior inclination of the glenoid. MATERIALS AND
      METHODS: Patients aged younger than 40 years who underwent arthroscopic shoulder
      stabilization (study group) were compared with patients (control group) who had
      previously undergone magnetic resonance imaging (MRI) for a different shoulder
      condition. Version was measured on axial images, and inclination was measured on
      coronal images of a T2-weighted spin-echo scan. The MRIs of 128 study group
      patients (mean age, 24.5 +/- 8.6 years) with a confirmed traumatic anterior
      shoulder dislocation were compared with the MRIs of 130 control group patients
      (mean age, 30.9 +/- 7 years). RESULTS: The mean version in the study group was 
      1.7 degrees  +/- 4.5 degrees  (retroversion); the mean inclination was 1.6
      degrees  +/- 5.9 degrees  (inferior). The mean version in the control group was 
      5.8 degrees  +/- 4.6 degrees  (retroversion); the mean inclination was -4.0
      degrees  +/- 6.8 degrees  (superior). The between-group differences were
      significant for version (P = .00001) and inclination (P = .00001). CONCLUSIONS:
      The results of this study strongly suggest that glenoid version and inclination
      are significantly increased in patients with established anterior shoulder
      instability compared with a matched control group.

PMID- 25958216
TI  - Differences in glenohumeral joint morphology between patients with anterior
      shoulder instability and healthy, uninjured volunteers.
AB  - BACKGROUND: Traumatic glenohumeral joint (GHJ) dislocations are common, resulting
      in significant shoulder disability and pain. Previous research indicates that
      bony morphology is associated with an increased risk of injury in other joints
      (eg, the knee), but the extent to which bony morphology is associated with
      traumatic GHJ dislocation is unknown. This study assessed GHJ morphology in
      patients with anterior GHJ instability and in a control population of healthy
      volunteers. METHODS: Bilateral computed tomography scans were used to measure GHJ
      morphology in both shoulders of 11 patients with instability and 11 control
      subjects. Specific outcome measures included the glenoid radius of curvature
      (ROC) in the anterior/posterior (A/P) and superior/inferior (S/I) directions,
      humeral head ROC, A/P and S/I conformity index, and A/P and S/I stability angle.
      RESULTS: Compared with the control subjects, the glenoid of the instability the
      injured shoulder in patients with instability was flatter (ie, higher ROC) in the
      A/P (P = .001) and S/I (P = .01) directions and this finding was also true for
      uninjured, contralateral shoulder (A/P: P = .01, S/I: P = .03). No differences in
      GHJ morphology were detected between the instability patients' injured and
      contralateral shoulders (P > .07). Similarly, no differences in GHJ morphology
      were detected between the control subjects' dominant and nondominant shoulders (P
      > .51). CONCLUSIONS: There are significant differences in GHJ morphology between
      healthy control subjects and both shoulders (injured and uninjured,
      contralateral) of patients diagnosed with anterior instability after GHJ
      dislocation. These findings are important clinically because they suggest that
      glenoid morphology may influence the risk of GHJ dislocation.

PMID- 25958218
TI  - Functional outcomes after shoulder resection: the patient's perspective.
AB  - BACKGROUND: Resection arthroplasty is a salvage procedure used for the treatment
      of deep-seated infections after total shoulder arthroplasty, hemiarthroplasty,
      and reverse total shoulder arthroplasty. Previous studies have reported a 50% to
      66% rate of pain relief after resection arthroplasty but with significant
      functional limitations. Our study aimed to qualify the perspective of the
      patients on their limitations and satisfaction with resection arthroplasty.
      METHODS: A retrospective record review of resection arthroplasties performed
      between September 2003 and December 2012 yielded 14 patients, and 7 completed the
      survey. The patients completed surveys with the focus on the "patient
      perspective." Functional scores, including American Shoulder and Elbow Surgeons,
      Simple Shoulder Test, Disabilities of the Arm, Shoulder, and Hand (DASH), DASH
      work, and DASH sports, were determined. RESULTS: Pain reduction and functional
      outcomes were similar to past reports of resection arthroplasty. Five of the 7
      patients (71%) reported satisfaction with their resection arthroplasty, and 6 of
      the 7 patients (86%) would undergo the procedure again if given the choice. Five
      of the 7 patients (71%) were able to most of activities of daily living.
      CONCLUSIONS: Patients in our study were generally satisfied with their resection
      arthroplasty. Resection arthroplasty is a reasonable option for treatment of deep
      seated periprosthetic infections or for patients with multiple previous failed
      procedures for total shoulder arthroplasty, hemiarthroplasty. and reverse
      shoulder arthroplasty.

PMID- 25958219
TI  - Hair cortisone level is associated with PTSD's dysphoric arousal symptoms in
      highly traumatized Chinese females.
AB  - BACKGROUND: Cortisone has been proposed as a useful additional biomarker for
      stress research. However, only very limited studies has investigated alterations
      of cortisone levels in stress-related mental disorder such as PTSD. The present
      study investigated the associations between PTSD symptomatology and hair
      cortisone levels which can reflect cumulative cortisone secretion over prolonged
      periods of time and is more robust to the influence of situational confounding.
      METHODS: Participants included 201 females who experienced 2008 Wenchuan
      earthquake and lost their children during the disaster. PTSD symptoms were
      assessed with the PTSD Checklist (PCL), and depression symptoms with the Center
      for epidemiological studies depression scale (CES-D). Hair cortisone levels were
      quantified by liquid chromatography tandem mass spectrometer. RESULTS: The
      results indicated that although hair cortisone secretion could not distinguish
      traumatized individuals with and without PTSD, it was uniquely linked to
      dysphoric arousal symptoms, a key aspect of the complex PTSD phenotype
      LIMITATIONS: A sample of females exposed to specific traumatic events was used,
      and PTSD was assessed using a self-reported measure. CONCLUSIONS: The findings
      provide preliminary evidence supporting the critical role of long-term cortisone
      changes in the development and maintenance of PTSD symptoms, and add to extant
      knowledge on the neuroendocrinological underpinnings of posttraumatic
      psychopathology.

PMID- 25958220
TI  - CCAAT/enhancer-binding protein delta (C/EBPdelta) aggravates inflammation and
      bacterial dissemination during pneumococcal meningitis.
AB  - BACKGROUND: The prognosis of bacterial meningitis largely depends on the severity
      of the inflammatory response. The transcription factor CAAT/enhancer-binding
      protein delta (C/EBPdelta) plays a key role in the regulation of the inflammatory
      response during bacterial infections. Consequently, we assessed the role of
      C/EBPdelta during experimental meningitis. METHODS: Wild-type and C/EBPdelta
      deficient mice (C/EBPdelta(-/-)) were intracisternally infected with
      Streptococcus pneumoniae and sacrificed after 6 or 30 h, or followed in a
      survival study. RESULTS: In comparison to wild-type mice, C/EBPdelta(-/-) mice
      showed decreased bacterial loads at the primary site of infection and decreased
      bacterial dissemination to lung and spleen 30 h after inoculation. Expression
      levels of the inflammatory mediators IL-10 and KC were lower in C/EBPdelta(-/-)
      brain homogenates, whereas IL-6, TNF-alpha, IL-1beta, and MIP-2 levels were not
      significantly different between the two genotypes. Moreover, C/EBPdelta(-/-) mice
      demonstrated an attenuated systemic response as reflected by lower IL-10, IL-6,
      KC, and MIP-2 plasma levels. No differences in clinical symptoms or in survival
      were observed between wild-type and C/EBPdelta(-/-) mice. CONCLUSION: C/EBPdelta
      in the brain drives the inflammatory response and contributes to bacterial
      dissemination during pneumococcal meningitis. C/EBPdelta does, however, not
      affect clinical parameters of the disease and does not confer a survival benefit.

PMID- 25958221
TI  - SWAT-1: The effectiveness of a 'site visit' intervention on recruitment rates in
      a multi-centre randomised trial.
AB  - BACKGROUND: Recruitment rates in multi-centre randomised trials often fall below
      target recruitment rates, causing problems for study outcomes. The Studies Within
      A Trial (SWAT) Programme, established by the All-Ireland Hub for Trials
      Methodology Research in collaboration with the Medical Research Council Network
      of Hubs in the United Kingdom and others, is developing methods for evaluating
      aspects of trial methodology through the conduct of research within research. A
      recently published design for a SWAT-1 provides a protocol for evaluating the
      effect of a site visit by the principal investigator on recruitment in multi
      centre trials. METHODS: Using the SWAT-1 design, the effect of a site visit, with
      the sole purpose of discussing trial recruitment, on recruitment rates in a large
      multicentre trial in the Republic of Ireland was evaluated. A controlled before
      and after intervention comparison was used, where the date of the site visit
      provides the time point for the intervention, and for the comparison to control
      sites. Site A received the intervention. Site B and Site C acted as the controls.
      Z-scores for proportions were calculated to determine within site recruitment
      differences. Odds ratios and 95% confidence intervals were calculated to
      determine between site recruitment differences. RESULTS: Recruitment rates were
      increased in Site A post-intervention (17% and 14% percentage point increases at
      1 and 3 months, respectively). No differences in recruitment occurred in Site B
      or in Site C. Comparing between site differences, at 3 months post-intervention,
      a statistically significant difference was detected in favour of higher
      recruitment in Site A (34% versus 25%; odds ratio 1.57, 95% confidence interval
      1.09 to 2.26). CONCLUSIONS: This is the first reported example of a study in the
      SWAT programme.. It provides evidence that a site visit, combined with a
      scheduled meeting, increases recruitment in a clinical trial. Using this example,
      other researchers might be encouraged to consider conducting a similar study,
      allowing the findings of future SWAT-1s to be compared and combined, so that
      higher level evidence on the effect of a site visit by the principal investigator
      can be obtained. THE ADCAR TRIAL: ISRCTN-96340041 ( www.controlled-trials.com );
      date of registration: 25 March 2008.

PMID- 25958222
TI  - MicrofoamTM model for simulated tendon repair.

PMID- 25958223
TI  - [MALDI-TOF mass spectrometry in clinical microbiology. Current situation and
      future perspectives].

PMID- 25958225
TI  - A support vector machine tool for adaptive tomotherapy treatments: Prediction of
      head and neck patients criticalities.
AB  - PURPOSE: Adaptive radiation therapy (ART) is an advanced field of radiation
      oncology. Image-guided radiation therapy (IGRT) methods can support daily setup
      and assess anatomical variations during therapy, which could prevent incorrect
      dose distribution and unexpected toxicities. A re-planning to correct these
      anatomical variations should be done daily/weekly, but to be applicable to a
      large number of patients, still require time consumption and resources. Using
      unsupervised machine learning on retrospective data, we have developed a
      predictive network, to identify patients that would benefit of a re-planning.
      METHODS: 1200 MVCT of 40 head and neck (H&N) cases were re-contoured,
      automatically, using deformable hybrid registration and structures mapping.
      Deformable algorithm and MATLAB((r)) homemade machine learning process,
      developed, allow prediction of criticalities for Tomotherapy treatments. RESULTS:
      Using retrospective analysis of H&N treatments, we have investigated and
      predicted tumor shrinkage and organ at risk (OAR) deformations. Support vector
      machine (SVM) and cluster analysis have identified cases or treatment sessions
      with potential criticalities, based on dose and volume discrepancies between
      fractions. During 1st weeks of treatment, 84% of patients shown an output
      comparable to average standard radiation treatment behavior. Starting from the
      4th week, significant morpho-dosimetric changes affect 77% of patients,
      suggesting need for re-planning. The comparison of treatment delivered and ART
      simulation was carried out with receiver operating characteristic (ROC) curves,
      showing monotonous increase of ROC area. CONCLUSIONS: Warping methods, supported
      by daily image analysis and predictive tools, can improve personalization and
      monitoring of each treatment, thereby minimizing anatomic and dosimetric
      divergences from initial constraints.

PMID- 25958226
TI  - Reflex epileptic mechanisms in humans: Lessons about natural ictogenesis.
AB  - The definition of reflex epileptic seizures is that specific seizure types can be
      triggered by certain sensory or cognitive stimuli. Simple triggers are sensory
      (most often visual, more rarely tactile or proprioceptive; simple audiogenic
      triggers in humans are practically nonexistent) and act within seconds, whereas
      complex triggers like praxis, reading and talking, and music are mostly cognitive
      and work within minutes. The constant relation between a qualitatively, often
      even quantitatively, well-defined stimulus and a specific epileptic response
      provides unique possibilities to investigate seizure generation in natural human
      epilepsies. For several reflex epileptic mechanisms (REMs), this has been done.
      Reflex epileptic mechanisms have been reported less often in focal lesional
      epilepsies than in idiopathic "generalized" epilepsies (IGEs) which are primarily
      genetically determined. The key syndrome of IGE is juvenile myoclonic epilepsy
      (JME), where more than half of the patients present reflex epileptic traits
      (photosensitivity, eye closure sensitivity, praxis induction, and language
      induced orofacial reflex myocloni). Findings with multimodal investigations of
      cerebral function concur to indicate that ictogenic mechanisms in IGEs largely
      (ab)use preexisting functional anatomic networks (CNS subsystems) normally
      serving highly complex physiological functions (e.g., deliberate complex actions
      and linguistic communication) which supports the concept of system epilepsy.
      Whereas REMs in IGEs, thus, are primarily function-related, in focal epilepsies,
      they are primarily localization-related. This article is part of a Special Issue
      entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From
      Experimental Models to the Clinic".

PMID- 25958227
TI  - A simple behavioral-developmental checklist versus formal screening for children
      in an epilepsy center.
AB  - We compare a 7-item checklist for developmental and behavioral concerns to formal
      screening with the Ages & Stages Questionnaires, Third Edition (ASQ-3) in
      children aged 1-5.5years old seen in a tertiary epilepsy care setting. The
      checklist was derived from a 35-item parent questionnaire used as a routine
      component of pediatric neuropsychology evaluations at our center. In our sample
      of 104 children, having even one checklist item endorsed was associated with a
      97% (66/68) positive predictive value for screening positive on the ASQ-3. Fifty
      percent of children for whom no items were endorsed on the checklist scored
      negative for developmental concerns on the ASQ-3. The overall sensitivity of the
      checklist to a positive ASQ-3 screen was 83%, and the specificity was 88%. Use of
      this simple checklist may facilitate screening in the outpatient epilepsy care
      setting where time and resources are often limited. 

PMID- 25958224
TI  - The cis and trans effects of the risk variants of coronary artery disease in the
      Chr9p21 region.
AB  - BACKGROUND: Recent genome-wide association studies (GWAS) have shown that single
      nucleotide polymorphisms (SNPs) in the Chr9p21 region are associated with
      coronary artery disease (CAD). Most of the SNPs identified in this region are non
      coding SNPs, suggesting that they may influence gene expression by cis or trans
      mechanisms to affect disease susceptibility. Since all cells from an individual
      have the same DNA sequence variations, levels of gene expression in immortalized
      cell lines can reflect the functional effects of DNA sequence variations that
      influence or regulate gene expression. The objective of this study is to evaluate
      the functional consequences of the risk variants in the Chr9p21 region on gene
      expression. METHODS: We examined the association between the variants in the
      Chr9p21 region and the transcript-level mRNA expression of the adjacent genes
      (cis) as well as all other genes across the whole genome (trans) from transformed
      beta-lymphocytes in 801 non-Hispanic white participants from The Genetic
      Epidemiology Network of Arteriopathy (GENOA) study. RESULTS: We found that the
      CAD risk variants in the Chr9p21 region were significantly associated with the
      mRNA expression of the ANRIL transcript ENST00000428597 (p = 8.58e-06).
      Importantly, a few distant transcripts were also found to be associated with the
      variants in this region, including the well-known CAD risk gene ABCA1 (p = 1.01e
      05). Gene enrichment testing suggests that retinol metabolism, N-Glycan
      biosynthesis, and TGF signaling pathways may be involved. CONCLUSION: These
      results suggest that the effect of risk variants in the Chr9p21 region on
      susceptibility to CAD is likely to be mediated through both cis and trans
      mechanisms.

PMID- 25958228
TI  - Status epilepticus, blood-brain barrier disruption, inflammation, and
      epileptogenesis.
AB  - Over the last 15 years, attention has been focused on dysfunction of the cerebral
      vasculature and inflammation as important players in epileptogenic processes,
      with a specific emphasis on failure of the blood-brain barrier (BBB; Fig. 1)
      (Seiffert et al., 2004; Marchi et al., 2007; Oby and Janigro, 2006; van Vliet et
      al., 2014; Vezzani et al., 2011) [3-7]. Here, we discuss how the BBB is disrupted
      as a consequence of SE and how this BBB breakdown may be involved in
      epileptogenesis. This article is part of a Special Issue entitled "Status
      Epilepticus".

PMID- 25958229
TI  - Can an exercise bicycle be safely used in the epilepsy monitoring unit?: An
      exercise method to provoke epileptic seizures and the related safety issues.
AB  - BACKGROUND AND PURPOSE: Long-term videoelectroencephalogram (video-EEG)
      monitoring is performed to diagnose an epileptic seizure and to investigate the
      differential diagnosis of paroxysmal events. To provoke an epileptic seizure, an
      exercise method is performed in some cases during long-term video-EEG recording
      in the epilepsy monitoring unit (EMU). The purpose of this study was two-fold: to
      assess the frequency and severity of adverse events associated with the use of an
      exercise bicycle and to find a way to safely use it in the EMU. METHODS: A
      retrospective survey was performed on all epileptic seizure videos recorded in
      the EMU from January 2012 to December 2013. Three hundred and fifty patients were
      included in this study. RESULTS: Eleven patients experienced an epileptic seizure
      while riding the exercise bicycle in the EMU. One patient's foot got stuck
      between the cycling pedal and its strap, and one patient fell off the exercise
      bicycle during the epileptic seizure. However, there were no serious adverse
      events over two years. CONCLUSION: Epileptic seizures were not frequent while
      riding the exercise bicycle, and serious injuries did not occur. But, there is a
      need to improve the safety in the EMU to control the potentially dangerous
      factors associated with the use of the exercise bicycle and to continuously
      monitor the patients with help from the staff.

PMID- 25958232
TI  - Role of IGF-1 in cortical plasticity and functional deficit induced by
      sensorimotor restriction.
AB  - In the adult rat, sensorimotor restriction by hindlimb unloading (HU) is known to
      induce impairments in motor behavior as well as a disorganization of
      somatosensory cortex (shrinkage of the cortical representation of the hindpaw,
      enlargement of the cutaneous receptive fields, decreased cutaneous sensibility
      threshold). Recently, our team has demonstrated that IGF-1 level was decreased in
      the somatosensory cortex of rats submitted to a 14-day period of HU. To determine
      whether IGF-1 is involved in these plastic mechanisms, a chronic cortical
      infusion of this substance was performed by means of osmotic minipump. When
      administered in control rats, IGF-1 affects the size of receptive fields and the
      cutaneous threshold, but has no effect on the somatotopic map. In addition, when
      injected during the whole HU period, IGF-1 is interestingly implied in cortical
      changes due to hypoactivity: the shrinkage of somatotopic representation of
      hindlimb is prevented, whereas the enlargement of receptive fields is reduced.
      IGF-1 has no effect on the increase in neuronal response to peripheral
      stimulation. We also explored the functional consequences of IGF-1 level
      restoration on tactile sensory discrimination. In HU rats, the percentage of paw
      withdrawal after a light tactile stimulation was decreased, whereas it was
      similar to control level in HU-IGF-1 rats. Taken together, the data clearly
      indicate that IGF-1 plays a key-role in cortical plastic mechanisms and in
      behavioral alterations induced by a decrease in sensorimotor activity. 

PMID- 25958233
TI  - The possible relationship between expressions of TRPC3/5 channels and cognitive
      changes in rat model of chronic unpredictable stress.
AB  - Transient receptor potential canonical channel (TRPC) is a nonselective cation
      channel dominantly permeable to Ca(2+). It consists of seven homologues, TRPC1
      TRPC7, based on their sequence similarity. According to some researches, the
      expression of TRPC3/5 in hippocampus is related to the morphological changes of
      hippocampus, including axon length and dendritic spine density [1]. This study
      observed whether the expression of TRPC3/5 was changed in chronic unpredictable
      stress (CUS)-induced depression of rat model and can the altered TRPC3/5
      expression affect the morphology of neurons in hippocampus of depressive rats as
      well as the cognitive ability. A total of 16 rats were equally and randomly
      divided into two groups: the control group and the depression model group, which
      underwent a process of CUS for three weeks. Western blot assay was conducted to
      test the content of TRPC3/5 in hippocampus, and Golgi-Cox staining was used to
      observe the morphological changes of neurons in hippocampus. Morris water maze
      (MWM) test was performed to observe the changes of spatial cognitive ability of
      rats while the long-term potentiation was applied to evaluate synaptic
      plasticity. Results showed that there was a difference in the expression of
      TRPC3/5 in hippocampal neurons, as well as the neuron morphology between control
      group and depression model group. At the same time the cognitive ability and
      synaptic plasticity were significantly changed. Results suggest that there is an
      association between expressions of TRPC3/5 and cognitive changes in CUS rat
      model, and the mechanism maybe that the different expressions of TRPC3/5 can
      cause morphological changes of the neurons in hippocampus, which has a profound
      impact on the spatial cognitive ability and synaptic plasticity. 

PMID- 25958230
TI  - Cerebrospinal fluid tau proteins in status epilepticus.
AB  - Tau protein is a phosphorylated microtubule-associated protein, principally
      localized at neuronal level in the central nervous system (CNS). Tau levels in
      the cerebrospinal fluid (CSF) are considered to index both axonal and neuronal
      damage. To date, however, no study has specifically evaluated the CSF levels of
      tau proteins in patients with status epilepticus (SE). We evaluated these
      established biomarkers of neuronal damage in patients with SE who received a
      lumbar puncture during SE between 2007 and 2014. Status epilepticus cases due to
      acute structural brain damage, including CNS infection, were excluded. Clinical,
      biological, therapeutic, and follow-up data were collected. Group comparison
      between patients stratified according to SE response to antiepileptic drugs
      (AEDs), disability, and epilepsy outcomes were performed. Twenty-eight patients
      were considered for the analyses (mean age 56 years): 14 patients had abnormally
      high CSF t-tau level, six patients had abnormally high CSF p-tau level, and only
      three patients had abnormally low Abeta1-42 level. Cerebrospinal fluid t-tau
      value was higher in patients who developed a refractory SE compared to patients
      with seizures controlled by AED. Cerebrospinal fluid t-tau values were positively
      correlated with SE duration and were higher in patients treated with propofol
      anesthesia compared to patients that had not received this treatment. Patients
      with higher CSF t-tau had higher risk of developing disability (OR = 32.5, p =
      0.004) and chronic epilepsy (OR = 12; p = 0.016) in comparison with patients with
      lower CSF t-tau level. Our results suggest that CSF t-tau level might be proposed
      as a biomarker of SE severity and prognosis. Prospective studies are needed to
      evaluate the effects of propofol on tau pathology in this setting. This article
      is part of a Special Issue entitled "Status Epilepticus".

PMID- 25958231
TI  - Thymol produces an antidepressant-like effect in a chronic unpredictable mild
      stress model of depression in mice.
AB  - Thymol, a bioactive monoterpene isolated from Thymus vulgaris, has displayed
      inspiring neuroprotective properties. The present study was designed to evaluate
      the antidepressant-like effects of thymol on a chronic unpredictable mild stress
      (CUMS) model of depression in mice and explore the underlying mechanisms. It was
      observed that thymol treatment (15 mg/kg and 30 mg/kg) significantly reversed the
      decrease of sucrose consumption, the loss of body weight, the reduction of
      immobile time in the tail suspension tests (TST) and forced swimming tests (FST)
      induced by CUMS paradigm. The levels of norepinephrine (NE) and serotonin (5-HT)
      in the hippocampus decreased in the CUMS-treated mice. Chronic treatments with
      thymol significantly restored the CUMS-induced alterations of monoamine
      neurotransmitters in the hippocampus. Our results further demonstrated that
      thymol administration negatively regulated the induction of proinflammatory
      cytokines including interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha
      in CUMS mice. Furthermore, thymol inhibited the activation of nod-like receptor
      protein 3 (NLRP3) inflammasome and its adaptor, and subsequently decreased the
      expression of caspase-1. In sum, our findings suggested that thymol played a
      potential antidepressant role in CUMS mice model through up-regulating the levels
      of central neurotransmitters and inhibiting the expressions of proinflammatory
      cytokines, which might provide potential for thymol in the light of opening up
      new therapeutic avenues for depression.

PMID- 25958235
TI  - Heteromeric Geranyl(geranyl) Diphosphate Synthase Is Involved in Monoterpene
      Biosynthesis in Arabidopsis Flowers.

PMID- 25958234
TI  - Predictors of symptom experience in Korean patients with cancer undergoing
      chemotherapy.
AB  - PURPOSE: This study aimed to investigate symptom experience and identify the
      predictors of symptom experience in cancer patients undergoing chemotherapy.
      METHOD: This study was a cross-sectional and descriptive design. A total of 167
      participants were recruited from the outpatient department of a university
      hospital in South Korea. Symptom experience (symptom prevalence, severity, and
      interference with daily activities), physiological factors (absolute neutrophil
      count, hemoglobin), psychological factors (depression, fighting spirit), and a
      situational factor (social support), based on the Theory of Unpleasant Symptoms,
      were measured. Descriptive statistics and multiple regression analyses were
      performed. RESULTS: Symptom prevalence ranged from 74.3% to 98.8% of patients.
      The five most severe symptoms were fatigue, numbness/tingling, dry mouth, sleep
      disturbance, and drowsiness. General activity and work were the most affected
      areas of daily life. Symptom experience was significantly related to hemoglobin,
      depression, fighting spirit, and social support. In the multiple regression
      analysis, higher level of depression and lung cancer accounted for 20.2% of the
      variance in symptom severity. Higher level of depression, lower level of fighting
      spirit and third or fourth-line chemotherapy accounted for 31.0% of the variance
      in symptom interference. CONCLUSIONS: Attention is drawn to developing a
      comprehensive approach which considers relevant physiological, psychological and
      social factors in assessment and management of concurrent symptoms in cancer
      patients undergoing chemotherapy. Health care professionals need to play a key
      role in helping patients deal with depressive mood and promote fighting spirit,
      particularly in patients with lung cancer or patients treated with higher-line
      chemotherapy, for controlling their symptom experience.

PMID- 25958236
TI  - Crystal Structures of GUN4 in Complex with Porphyrins.

PMID- 25958237
TI  - A 1-year follow-up evaluation of a sexual-health education program for Spanish
      adolescents compared with a well-established program.
AB  - BACKGROUND: Competencies for adolescents with a healthy sexuality (COMPAS) is the
      only school-based sexual health promotion program in Spain that has been found to
      be as effective as an evidence-based intervention (!Cuidate!) in the short term.
      This study's aim was to compare data from a 12-month follow-up evaluation on the
      effects of COMPAS on adolescents' sexual risks (knowledge, attitudes, perceived
      norms, sexual risk perception and intentions) and sexual behaviours (age of the
      first sex, consistent condom use and multiple partners) with an evidence-based
      intervention (!Cuidate!) and a control group. METHODS: Eighteen schools from five
      provinces of Spain were randomly assigned to one of three conditions: COMPAS,
      !Cuidate! and a control group. The adolescents (N = 1563; 34% attrition) were
      evaluated 1 week before and after the program, and 1 year post-program
      implementation. RESULTS: We found that the COMPAS program was as effective as
      !Cuidate!, the evidence-based program, in increasing the adolescents' knowledge
      about sexually transmitted infections and in fostering favourable attitudes about
      condom use and people living with HIV/AIDS. COMPAS was more effective than
      !Cuidate! in increasing the adolescents' perceptions of their peer's consistent
      condom use and the age delay of their first vaginal intercourse. However, it was
      less effective in maintaining the adolescents' intentions to use condoms and in
      delaying the age of their first oral sex experience. CONCLUSION: COMPAS was as
      effective as !Cuidate! in reducing sexual risk among adolescents.

PMID- 25958238
TI  - Trends in tobacco-attributable mortality in France.
AB  - BACKGROUND: In 2010, the prevalence of tobacco use in France was 33% and reached
      39% in the population aged 18-44. The purpose of this article is to describe the
      trends in tobacco-attributable mortality in France between 1980 and 2010.
      METHODS: Using data from the national mortality statistics and relative risks of
      death, we estimated the tobacco-attributable fractions (AF) by sex and age using
      the method developed by Peto et al. and used recently by the World Health
      Organization with improved relative risk estimates. The tobacco-attributable
      mortality by age and sex is obtained by multiplying the AFs by the number of
      deaths. They are estimated in 5-year intervals from 1980 to 2010. RESULTS: In
      2010, a total of 78,000 deaths were attributable to tobacco use in France. The
      number of deaths attributable to tobacco use among men decreased from 66,000
      deaths in 1985 to 59,000 deaths in 2010, and the tobacco-AF decreased from 23% in
      1985 to 21% in 2010. The number of deaths attributable to tobacco use among women
      increased from 2700 in 1980 (1% of all deaths) to 19,000 in 2010 (7% of all
      deaths). In the population aged 35-69, one in three deaths among men and one in
      seven deaths among women are attributable to tobacco use. CONCLUSION: While
      tobacco-attributable mortality among men has been declining during the past three
      decades, it has increased dramatically among women. Thus, effective preventive
      measures are urgently needed to stem the tobacco epidemic.

PMID- 25958239
TI  - The negative effect of financial constraints on planning prevention activities:
      some evidence from the Italian experience.
AB  - This study was aimed to assess the association between regional financial
      deficits and Recovery Plans and the quality of the 702 projects developed by the
      Italian Regions within the National Prevention Plan 2010-13. Multivariate
      analyses showed significant associations between Recovery Plans and low quality
      of projects, possibly due to weak regional public health capacities. Regions with
      Recovery Plans are likely to focus mainly on short-term issues with a high impact
      on health care costs, leaving few resources available for prevention. A different
      approach to financial deficit focused on long-term strategies, including those
      for health promotion and disease prevention, is needed. 

PMID- 25958240
TI  - Are there socioeconomic differences in outcomes of coronary revascularizations--a
      register-based cohort study.
AB  - BACKGROUND: Earlier studies have reported socioeconomic differences in coronary
      heart disease incidence and mortality and in coronary treatment, but less is
      known about outcomes of care. We examined trends in income group differences in
      outcomes of coronary revascularizations among Finnish residents in 1998-2010.
      METHODS: First revascularizations for 45-84-year-old Finns were extracted from
      the Hospital Discharge Register in 1998-2009 and followed until 31 December 2010.
      Income was individually linked to them and adjusted for family size. We examined
      the risk of major adverse cardiac events (MACEs), coronary mortality and re
      revascularization. We calculated age-standardized rates with direct method and
      Cox regression models. RESULTS: Altogether 69 076 men and 27 498 women underwent
      revascularization during the study period. Among men [women] in the 1998 cohort,
      41% [35%] suffered MACE during 29 days after the operation and 30% [28%] in the
      2009 cohort. Myocardial infarction mortality within 1 year was 2% among both
      genders in both cohorts. Among men [women] 9% [14%] underwent revascularization
      within 1 year after the operation in 1998 and 12% [12%] in 2009. Controlling for
      age, co-morbidities, year, previous infarction and disease severity, an inverse
      income gradient was found in MACE incidence within 29 days and in coronary
      mortality. The excess MACE risk was 1.39 and excess mortality risk over 1.70
      among both genders in the lowest income quintile. All income group differences
      remained stable from 1998 to 2010. CONCLUSIONS: In health care, more attention
      should be paid to prevention of adverse outcomes among persons with low
      socioeconomic position undergoing revascularization.

PMID- 25958241
TI  - An evaluation of three statistical estimation methods for assessing health policy
      effects on prescription drug claims.
AB  - BACKGROUND: While the choice of analytical approach affects study results and
      their interpretation, there is no consensus to guide the choice of statistical
      approaches to evaluate public health policy change. OBJECTIVES: This study
      compared and contrasted three statistical estimation procedures in the assessment
      of a U.S. Food and Drug Administration (FDA) suicidality warning, communicated in
      January 2008 and implemented in May 2009, on antiepileptic drug (AED)
      prescription claims. METHODS: Longitudinal designs were utilized to evaluate
      Oklahoma (U.S. State) Medicaid claim data from January 2006 through December
      2009. The study included 9289 continuously eligible individuals with prevalent
      diagnoses of epilepsy and/or psychiatric disorder. Segmented regression models
      using three estimation procedures [i.e., generalized linear models (GLM),
      generalized estimation equations (GEE), and generalized linear mixed models
      (GLMM)] were used to estimate trends of AED prescription claims across three time
      periods: before (January 2006-January 2008); during (February 2008-May 2009); and
      after (June 2009-December 2009) the FDA warning. RESULTS: All three statistical
      procedures estimated an increasing trend (P < 0.0001) in AED prescription claims
      before the FDA warning period. No procedures detected a significant change in
      trend during (GLM: -30.0%, 99% CI: -60.0% to 10.0%; GEE: -20.0%, 99% CI: -70.0%
      to 30.0%; GLMM: -23.5%, 99% CI: -58.8% to 1.2%) and after (GLM: 50.0%, 99% CI: 
      70.0% to 160.0%; GEE: 80.0%, 99% CI: -20.0% to 200.0%; GLMM: 47.1%, 99% CI: 
      41.2% to 135.3%) the FDA warning when compared to pre-warning period.
      CONCLUSIONS: Although the three procedures provided consistent inferences, the
      GEE and GLMM approaches accounted appropriately for correlation. Further,
      marginal models estimated using GEE produced more robust and valid population
      level estimations.

PMID- 25958242
TI  - An antibacterial ortho-quinone diterpenoid and its derivatives from Caryopteris
      mongolica.
AB  - To identify antibacterial components in traditional Mongolian medicinal plant
      Caryopteris mongolica, an ortho-quinone abietane caryopteron A (1) and three its
      derivatives caryopteron B-D (2-4) were isolated from the roots of the plant
      together with three known abietanes demethylcryptojaponol (5), 6alpha
      hydroxydemethyl cryptojaponol (6), and 14-deoxycoleon U (7). The chemical
      structures of these abietane derivatives were elucidated on the basis of
      spectroscopic data. Compounds 1-4 had C-13 methylcyclopropane substructures, and
      2-4 had a hexanedioic anhydride ring C instead of ortho-quinone in 1. The
      stereochemistry of these compound was assumed from NOE spectra and ECD Cotton
      effects. Compounds 1 and 5-7 showed antibacterial activities against the Gram
      positive bacteria Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus
      faecalis, and Micrococcus luteus, being 1 the more potent. 

PMID- 25958243
TI  - Anticancer drug-based multifunctional nanogels through self-assembly of dextran
      curcumin conjugates toward cancer theranostics.
AB  - Curcumin (CCM) has been received much attention in cancer theranostics because
      CCM exhibits both anticancer activity and strong fluorescence available for bio
      imaging. However, CCM has never been utilized in clinical mainly due to its
      extremely low water solubility and its low cellular uptake into cancer cells. We
      fabricated novel CCM-based biodegradable nanoparticles through self-assembly of
      amphiphilic dextran-CCM conjugates. Significantly high CCM loading contents in
      the nanoparticles and the high water solubility were achieved. Importantly, the
      dextran-CCMs nanoparticles were effectively delivered into HeLa cells and
      exhibited strong fluorescence available for live-cell imaging, although the
      nanoparticles were not delivered into normal cells. Thus, the dextran-CCMs
      nanoparticles could be a promising for creation of novel CCM-based cancer
      theranostics with high efficacy. 

PMID- 25958244
TI  - Novel natural-product-like caged xanthones with improved druglike properties and
      in vivo antitumor potency.
AB  - DDO-6101, a natural-product-like caged xanthone discovered previously in our
      laboratory based on the pharmacophoric scaffold of Garcinia natural product
      gambogic acid (GA), shows potent cytotoxicity in vitro but poor efficacy in vivo
      due to its poor druglike properties. In order to improve the druglike properties
      and in vivo cytotoxic potency, a novel series of 19 prenyl group-modified
      derivatives of DDO-6101 was synthesized and evaluated for their in vitro
      antitumor activity and druglike properties. The SAR and SPR information of these
      compounds was also obtained. In the light of the in vitro antitumor activity and
      druglike properties such as aqueous solubility and permeability, compound 6f
      (named as DDO-6306) was advanced into in vivo efficacy experiment. The results
      showed that DDO-6306 is more potent than DDO-6101 in vivo and is a promising
      antitumor candidate for further evaluation. 

PMID- 25958245
TI  - Discovery of bisamide-heterocycles as inhibitors of scavenger receptor BI (SR-BI)
      mediated lipid uptake.
AB  - A new series of potent inhibitors of cellular lipid uptake from HDL particles
      mediated by scavenger receptor, class B, type I (SR-BI) was identified. The
      series was identified via a high-throughput screen of the National Institutes of
      Health Molecular Libraries Small Molecule Repository (NIH MLSMR) that measured
      the transfer of the fluorescent lipid DiI from HDL particles to CHO cells
      overexpressing SR-BI. The series is characterized by a linear peptidomimetic
      scaffold with two adjacent amide groups, as well as an aryl-substituted
      heterocycle. Analogs of the initial hit were rapidly prepared via Ugi 4-component
      reaction, and select enantiopure compounds were prepared via a stepwise sequence.
      Structure-activity relationship (SAR) studies suggest an oxygenated arene is
      preferred at the western end of the molecule, as well as highly lipophilic
      substituents on the central and eastern nitrogens. Compound 5e, with (R)
      stereochemistry at the central carbon, was designated as probe ML279. Mechanistic
      studies indicate that ML279 stabilizes the interaction of HDL particles with SR
      BI, and its effect is reversible. It shows good potency (IC50=17 nM), is non
      toxic, plasma stable, and has improved solubility over our alternative probe
      ML278.

PMID- 25958246
TI  - Magnetic resonance imaging of tumor with a self-traceable polymer conjugated with
      an antibody fragment.
AB  - A (13)C-enriched phosphorylcholine polymer ((13)C-PMPC) as a self-traceable MR
      (magnetic resonance) tag was conjugated with a fragment (scFv) of Herceptin, a
      clinical antibody against antigen Her2. When injected in model mice bearing
      Her2(+) (gastric) and Her2(-) (pancreatic) tumors, the antibody-tag conjugate
      (13)C-PMPC-scFv selectively accumulated in the Her2(+) tumor with a rapid build
      up/decay (accumulation/clearance) profile and, with the use of the (1)H-(13)C
      double-resonance (heteronuclear correlation) technique, the Her2(+) gastric tumor
      was clearly MR imaged. 

PMID- 25958247
TI  - Synthesis and studies on the mGluR agonist activity of FAP4 stereoisomers.
AB  - The four stereoisomers of 1-amino-2-fluoro-2-(phosphonomethyl)cyclopropane-1
      carboxylic acid (FAP4) were synthesized via diastereoselective Rh(II)-catalysed
      cyclopropanation of a phosphonylated fluoroalkene. Different isomers of FAP4 and
      the corresponding non-fluorinated analogs showed a similar pharmacological
      profile against the isoforms of metabotropic glutamate receptor (mGluR). Within
      the fluorinated series, (-)-(Z)-FAP4 and (-)-(E)-FAP4 demonstrated the highest
      agonist activity against mGlu4 (EC50 0.10 MUM). Our results suggest that
      fluorocyclopropanes bearing an amino-acid function can be suitable for the
      development of potent conformationally restricted mGluR agonists.

PMID- 25958248
TI  - Synthesis, cytotoxicity and haemolytic activity of Pulsatilla saponin A, D
      derivatives.
AB  - The strong haemolytic activity of Pulsatilla saponin A (PSA), D (PSD) hampered
      their clinical development of antitumor agents. In order to solve this problem, C
      28 position modification derivatives of PSA/PSD were synthesized. The
      cytotoxicity and haemolytic activity of these compounds were evaluated. Structure
      activity relationship and structure-toxicity relationship had been observed. The
      mice acute toxicity of compound 11 was reduced greatly than that of PSA. This
      study indicates that compound 11 may represent an interesting class of potent
      antitumor agents from triterpenoid saponins avoiding the haemolysis problem. The
      present study has important significance for the development of antitumor
      saponins. 

PMID- 25958249
TI  - Botulinum toxin in migraine: Role of transport in trigemino-somatic and trigemino
      vascular afferents.
AB  - Migraine secondary to meningeal input is referred to extracranial regions
      innervated by somatic afferents that project to homologous regions in the
      trigeminal nucleus caudalis (TNC). Reported efficacy of extracranial botulinum
      toxin (BoNT) in treating migraine is surprising since a local extracranial effect
      of BoNT cannot account for its effect upon meningeal input. We hypothesize that
      intradermal BoNT acts through central transport in somatic afferents.
      Anesthetized C57Bl/6 mice (male) received unilateral supraorbital (SO) injections
      of BoNT-B (1.5 U/40 MUl) or saline. 3 days later, mice received ipsilateral
      (ipsi)-SO capsaicin (20 MUl of 0.5mM solution) or meningeal capsaicin (4 MUl of
      0.35 MUM). Pre-treatment with ipsi-SO BoNT-B i) decreased nocicsponsive
      ipsilateral wiping behavior following ipsi-SO capsaicin; ii) produced cleavage of
      VAMP in the V1 region of ipsi-TG and in TG neurons showing WGA after SO
      injection; iii) reduced expression of c-fos in ipsi-TNC following ipsi-SO
      capsaicin; iv) reduced c-fos activation and NK-1 internalization in ipsi-TNC
      secondary to ipsi-meningeal capsaicin; and vi) SO WGA did not label dural
      afferents. We conclude that BoNT-B is taken up by peripheral afferents and
      transported to central terminals where it inhibits transmitter release resulting
      in decreased activation of second order neurons. Further, this study supports the
      hypothesis that SO BoNT exerts a trans-synaptic action on either the second order
      neuron (which receives convergent input from the meningeal afferent) or the
      terminal/TG of the converging meningeal afferent.

PMID- 25958250
TI  - Predictors of diagnostic success in image-guided pediatric soft-tissue biopsies.
AB  - BACKGROUND: Image-guided percutaneous core needle biopsy (PCNB) of soft-tissue
      lesions is a minimally invasive technique that can provide a definitive diagnosis
      for treatment. Anatomical and age considerations in children require judicious
      use of safe percutaneous biopsy techniques. There are, however, limited data on
      the determinants of diagnostic yield in soft-tissue lesions in this population.
      OBJECTIVES: To assess lesion-related and technical factors that affect diagnostic
      yield and safety in PCNB of pediatric soft-tissue lesions. MATERIALS AND METHODS:
      This was a retrospective cohort study of 205 PCNB performed from January 2000 to
      July 2014. Diagnostic yield and its associations with technical and lesion
      related factors were evaluated using bivariate analysis. RESULTS: The mean
      patient age was 11.1 +/- 6.9 years (interquartile range [IQR]: 4.3-16 years).
      Ultrasound guidance alone was used in 91% of cases. The mean number of passes was
      7.5 +/- 3.2 (IQR: 5-9 passes) per case. The overall diagnostic yield was 75% and
      the overall accuracy was 88%. Performing fewer than four passes was associated
      with a nondiagnostic biopsy (P = 0.001). There were no lesion or other technical
      factors that predicted a diagnostic biopsy. There were two complications (1%)
      over 14 years. CONCLUSION: Image-guided PCNB is a safe and effective means for
      the diagnosis of pediatric soft-tissue abnormalities. Aside from performing at
      least four passes, our data show no technical or lesion-related factors that
      increase diagnostic yield in pediatric PCNB of soft-tissue lesions.

PMID- 25958252
TI  - The potential role of biochar in the removal of organic and microbial
      contaminants from potable and reuse water: A review.
AB  - In this work, the potential benefits, economics, and challenges of applying
      biochar in water treatment operations to remove organic and microbial
      contaminants was reviewed. Minimizing the use of relatively more expensive
      traditional sorbents in water treatment is a motivating aspect of biochar
      production, e.g., $246/ton non-activated biochar to $1500/ton activated carbon.
      Biochar can remove organic contaminants in water, such as some pesticides (0.02
      23 mg g(-1)), pharmaceutical and personal care products (0.001-59 mg g(-1)), dyes
      (2-104 mg g(-1)), humic acid (60 mg g(-1)), perfluorooctane sulfonate (164 mg g(
      1)), and N-nitrosomodimethylamine (3 mg g(-1)). Including adsorption/filtration
      applications, biochar can potentially be used to inactivate Escherichia coli via
      disinfection, and transform 95% of 2-chlorobiphenyl via advanced oxidation
      processes. However, more sorption data using biochar especially at demonstration
      scale, for treating potable and reuse water in adsorption/filtration applications
      will help establish the potential of biochars to serve as surrogates for
      activated carbons.

PMID- 25958251
TI  - A model to explain suicide by self-immolation among Iranian women: A grounded
      theory study.
AB  - INTRODUCTION: Self-immolation is a common method of suicide among Iranian women.
      There are several contributing motives for attempting self-immolation, and
      exploration of the process of self-immolation incidents will help
      interventionists and clinicians develop prevention programs. METHODS: A grounded
      theory study using face-to-face, recorded interviews was conducted with surviving
      self-immolated patients (n=14), their close relatives (n=5), and medical staff
      (n=8) in Kermanshah, Iran. Data were analyzed using constant comparison in open,
      axial, and selective coding stages. RESULTS: A conceptual model was developed to
      explain the relationships among the main categories extracted through the
      grounded theory study. Family conflicts emerged as the core category. Cultural
      context of self-immolated patients offered a contextual condition. Other
      important categories linked to the core category were mental health problems,
      distinct characteristics of the suicidal method, and self-immolation as a threat.
      The role of mental health problems as a causal condition was detected in
      different levels of the self-immolation process. Finally, adverse consequences of
      self-immolation emerged as having important impact. CONCLUSION: The conceptual
      model, derived through grounded theory study, can guide design of prevention
      programs. The pivotal role of family conflicts should be emphasized in mental
      health interventions. The impact of adverse consequences of self-immolation on
      further suicidal processes necessitates post-suicide prevention programs. Further
      research to design specific interventions is recommended.

PMID- 25958254
TI  - Vanadium(V) and -(IV) complexes of anionic polysaccharides: Controlled release
      pharmaceutical formulations and models of vanadium biotransformation products.
AB  - Uncontrolled reactions in biological media are a main obstacle for clinical
      translation of V-based anti-diabetic or anti-cancer pro-drugs. We investigated
      the use of controlled-release pharmaceutical formulations to ameliorate this
      issue with a series of V(V) and (IV) complexes of anionic polysaccharides.
      Carboxymethyl cellulose, xanthan gum, or alginic acid formulations were prepared
      by the reactions of [VO4](3-) with one or two molar equivalents of biological
      reductants, L-ascorbic acid (AA) or L-cysteine (Cys), in the presence of excess
      polysaccharide at pH~7 or pH~4. XANES studies with the use of a previously
      developed library of model V(V), V(IV) and V(III) complexes showed that reactions
      in the presence of AA led mostly to the mixtures of five- and six-coordinate
      V(IV) species, while the reactions in the presence of Cys led predominantly to
      the mixtures of five- and six-coordinate V(V) species. The XANES spectra of some
      of these samples closely matched those reported previously for [VO4](3-)
      biotransformation products in isolated blood plasma, red blood cells, or cultured
      adipocytes, which supports the hypothesis that modified polysaccharides are major
      binders of V(V) and V(IV) in biological systems. Studies by EPR spectroscopy
      suggested predominant V(IV)-carboxylato binding in complexes with
      polysaccharides. One of the isolated products (a V(IV)-alginato complex) showed
      selective release of low-molecular-mass V species at pH~8, but not at pH~2, which
      makes it a promising lead for the development of V-containing formulations for
      oral administration that are stable in the stomach, but release the active
      ingredient in the intestines. 

PMID- 25958253
TI  - Activating tert-butyl hydroperoxide by chelated vanadates for stereoselectively
      preparing sidechain-functionalized tetrahydrofurans.
AB  - tert-Butyl hydroperoxide (TBHP) stereoselectively oxidizes substituted 4
      pentenols, when activated by (ethyl)[cis-(piperidine-2,6-diyl)dimethyl]
      vanadates. The reaction affords (tetrahydrofuran-2-yl)methanols in up to 89%
      yield, and in stereoselectivity ranging between moderate (cis:trans=32:68) to
      excellent (>99:1). Correlating structures of 4-pentenols, differing by
      substitution at tetragonal and trigonal stereocenters, to configuration of
      products obtained from oxidative cyclization provides a reaction model explaining
      the origin of stereoselectivity by (i) intramolecular oxygen atom transfer to
      (ii) a chair-like folded alkenol, being (iii) hydrogen-bonded to one of the two
      aminodiolate oxygens of the chelated vanadate, having (iv) substituents in the
      chair-like transition structure preferentially aligned equatorially. Substituents
      at trigonal stereocenters improve 2,5-cis- and 2,4-trans-selectivity for
      oxidative 4-pentenol cyclization in case of (Z)-configuration. An (E)-substituent
      does not alter selectivity exerted by a terminal (Z)-substituent of similar
      steric size. Larger (E)-groups increase the fraction of 2,5-trans-cyclized
      products. The reaction model additionally implements results from vanadium-51 NMR
      spectroscopy and density functional theory. According to theory, the
      (dialkoxy)(oxo)vanadium substituent exerts in the preferred end-on conformation
      almost no effect on structure and bonding of the peroxide group in tert
      butylperoxy vanadates. Changing conformation to a higher in energy side-on
      arrangement puts the vanadate-bound tert-butylperoxy group into a position to
      serve in a concerted reaction as combined electron acceptor and oxygen atom
      donor. 

PMID- 25958256
TI  - Procollagen type III amino terminal peptide and myocardial fibrosis: A study in
      hypertensive patients with and without left ventricular hypertrophy.
AB  - INTRODUCTION AND OBJECTIVES: An exaggerated accumulation of type I and type III
      fibrillar collagens occurs throughout the free wall and interventricular septum
      of patients with primary hypertension and left ventricular hypertrophy (LVH). In
      the present study the serum concentration of procollagen type III amino terminal
      peptide (PIIIP) was measured to determine the value of this peptide as a
      potential marker of ventricular fibrosis in hypertensive patients, particularly
      those with LVH. METHODS: The study population consisted of patients with never
      treated mild to moderate essential hypertension and 30 normotensive control
      subjects. Clinical, echocardiographic, electrocardiographic and biochemical
      parameters were assessed in all patients. RESULTS: Heart rate, body mass index
      and levels of blood pressure were increased in hypertensives, particularly those
      with LVH, compared to normotensive controls. Posterior wall thickness, left
      ventricular (LV) mass and LV mass index, and serum PIIIP concentration were also
      increased in hypertensives, with significant differences between the two
      hypertensive groups. The ratio between maximal early and late transmitral flow
      velocity measured during diastole was lower in hypertensives, particularly those
      with LVH, than in normotensive controls. CONCLUSIONS: The increase in PIIIP
      indicates that type III collagen synthesis increases in hypertensives,
      particularly those with LVH, implying that alterations in the heart in
      hypertension are the result not solely of hypertrophied LV muscle, but also of
      increased collagen deposition within the ventricular wall and around the coronary
      vessels. Thus, measurement of serum PIIIP could be a practical and useful tool in
      the non-invasive assessment of myocardial remodeling in hypertension.

PMID- 25958255
TI  - Role of tubal surgery in the era of assisted reproductive technology: a committee
      opinion.
AB  - This document reviews surgical options for achieving patency in obstructed
      fallopian tubes and the factors that must be considered when deciding between
      surgical repair and IVF. This document replaces the document of the same name,
      last published in 2012 (Fertil Steril 2012;97:539-45).

PMID- 25958257
TI  - Aortic arch rescued through double-chimney technique.

PMID- 25958258
TI  - Syncope and hyperCKemia as minimal manifestations of short CTG repeat expansions
      in myotonic dystrophy type 1.
AB  - INTRODUCTION: Syncope and palpitations as the only initial manifestations of
      myotonic dystrophy type 1 (MD1) due to a CTG expansion of 50-100 repeats have not
      been reported. CASE REPORT: In a 55-year-old female with a family history of MD1
      and a personal history of a single syncope, palpitations, and hyperCKemia, 70 CTG
      repeats were detected in the DMPK gene. Her brother had presented atypical
      clinical, electromyographic, and muscle biopsy features since the age of 35 but
      had been diagnosed with MD1 after he later developed typical distal myotonia. He
      died suddenly during an episode of syncope at the age of 53. A sister with
      clinical myotonia died suddenly during sleep at the age of 45 and a second sister
      with quadriparesis died from complications of intestinal rupture at age 52. A
      third sister committed suicide at age 40 after developing recurrent syncopes,
      while a fourth sister had hyperCKemia and foot-extensor weakness. The mother of
      these five affected children died suddenly from myocardial rupture. CONCLUSIONS:
      MD1 with <100 CTG repeats may exclusively manifest cardiologically. Family
      screening for MD1 is important even in asymptomatic patients. MD1 may initially
      manifest without typical features, while muscle biopsy may be misleading and
      indicate glycogenosis. Close cardiac follow-up is important if MD1 manifests
      cardiologically to prevent syncope or sudden cardiac death.

PMID- 25958259
TI  - [Reply to the Letter to the Editor "Inflammation, systemic lupus erythematosus
      and the Kounis mast cell activation-associated syndrome"].

PMID- 25958260
TI  - Relationship between severity of pulmonary hypertension and coronary sinus
      diameter.
AB  - INTRODUCTION AND OBJECTIVE: We investigated the relationship between coronary
      sinus (CS) diameter and pulmonary artery systolic pressure (PASP) in patients
      with pulmonary hypertension (PH) and normal left ventricular systolic function.
      METHODS: A total of 155 participants referred for transthoracic echocardiography
      were included in the study. The study population consisted of 100 patients with
      chronic PH and 55 control subjects. Patients with PH were divided into two groups
      according to PASP: those with PASP 36-45 mmHg, the mild PH group (n=53); and
      those with PASP >45 mmHg, the moderate to severe PH group (n=47). CS diameter was
      measured from the posterior atrioventricular groove in apical 4-chamber view
      during ventricular systole according to the formula: mean CS=(proximal CS+mid
      CS+distal CS)/3. RESULTS: Mean CS diameter was significantly higher in the
      moderate to severe PH group than in the controls and in the mild PH group (1.12+/
      0.2 cm vs. 0.82+/-0.1 cm and 0.87+/-0.1 cm, respectively; p<0.001). It was
      significantly correlated with right atrial (RA) area (r=0.674, p<0.001), RA
      pressure (r=0.458, p<0.001), PASP (r=0.562, p<0.001), inferior vena cava diameter
      (r=0.416, p<0.001), right ventricular E/A ratio (r=-0.290, p<0.001), and E/Em
      ratio (r=0.235, p=0.004). RA area (beta=0.475, p<0.001) and PASP (beta=0.360,
      p=0.002) were found to be independent predictors of CS diameter. CONCLUSIONS: A
      dilated CS was associated with moderate to severe pulmonary hypertension, and RA
      area and PASP were independent predictors of CS diameter.

PMID- 25958261
TI  - Pathological effects of cyanobacteria on sea fans in southeast Florida.
AB  - In early August 2008, observations by divers indicated that sea fans,
      particularly Gorgonia ventalina, Gorgonia flabellum, and Iciligorgia schrammi,
      were being covered by benthic filamentous cyanobacteria. From August 2008 through
      January 2009 and again in April 2009, tissue samples from a targeted G. ventalina
      colony affected by cyanobacteria and from a nearby, apparently healthy (without
      cyanobacteria) control colony, were collected monthly for histopathological
      examination. The primary cellular response of the sea fan to overgrowth by
      cyanobacteria was an increase in the number of acidophilic amoebocytes (with
      their granular contents dispersed) that were scattered throughout the coenenchyme
      tissue. Necrosis of scleroblasts and zooxanthellae and infiltration of
      degranulated amoebocytes were observed in the sea fan surface tissues at sites
      overgrown with cyanobacteria. Fungal hyphae in the axial skeleton were
      qualitatively more prominent in cyanobacteria-affected sea fans than in controls.

PMID- 25958262
TI  - Lysinibacillus sphaericus binary toxin induces apoptosis in susceptible Culex
      quinquefasciatus larvae.
AB  - During sporulation, a Gram-positive bacterium Lysinibacillus sphaericus (Ls)
      produces the mosquito larvicidal binary toxin composed of 2 subunits, BinA and
      BinB. Full toxicity against Culex and Anopheles mosquito larvae is achieved when
      both subunits are administered together at equimolar amounts. Although cellular
      responses to Bin toxin have been reported in previous studies, it remains
      essential to extensively examine the cytopathic effects in vivo to define the
      underlying mechanism of larval death. In this study, 4th instar Culex
      quinquefasciatus larvae fed with different doses of Bin toxin were analyzed both
      for ultrastructural as well as biochemical effects. Typical morphological changes
      consistent with apoptosis were observed in mosquito larvae exposed to Bin toxin,
      including mitochondrial swelling, chromatin condensation, cytoplasmic
      vacuolization and apoptotic cell formation. Bin toxin also induced the activation
      of caspase-9 and caspase-3 in larval midgut cells. Our current observations thus
      suggest that Bin toxin triggers apoptosis via an intrinsic or mitochondrial
      pathway in vivo, possibly contributing to larval death. 

PMID- 25958263
TI  - Serious head trauma preceding essential tremor: A population-based study
      (NEDICES).
AB  - BACKGROUND: An association between head trauma and essential tremor (ET) has not
      been formally assessed. Our purpose was to assess the association between serious
      head trauma and ET. METHODS: History of head trauma was assessed in 274 ET cases
      and 3201 controls in the Neurological Disorders in Central Spain (NEDICES) study,
      a population-based study in central Spain. Head trauma was defined as serious
      only if the subject reported that the trauma resulted in loss of consciousness,
      hospitalization, or a visit to the emergency department. RESULTS: Thirty-two
      (11.7%) of 274 ET cases vs. 260 (8.1%) of 3201 controls reported a history of
      serious head trauma (p=0.04). In an adjusted logistic regression analysis,
      participants who reported serious head trauma were 52% more likely to have ET
      (odds ratio [OR] 1.52; 95% confidence interval [CI] 1.02-2.27, p=0.04). The odds
      of ET increased with increasing age of head trauma: adjusted ORs=1.23 (95% CI
      0.43-3.46, p = 0.70) for serious head trauma that occurred before age 18 years,
      adjusted OR=1.49 (95% CI 0.62-3.55, p = 0.37) for serious head trauma between
      ages 18 to 39 years, and adjusted OR=1.61 (95% CI 1.00-2.57, p = 0.04) for
      serious head trauma at age 40 years or older. CONCLUSIONS: Our study suggests
      that serious head trauma, especially when it occurs after 40 years, is associated
      with increased odds of ET. Additional studies are needed to reproduce this novel
      finding.

PMID- 25958264
TI  - Serial measurements of phosphorylated neurofilament-heavy in the serum of
      subjects with amyotrophic lateral sclerosis.
AB  - There is a need for a blood biomarker of disease activity in ALS. This marker
      needs to measure the loss of motor neurones. Phosphorylated neurofilament heavy
      chain (pNfH) in the serum is a biomarker of axonal injury. Previous studies have
      found that levels of pNfH are elevated in ALS. We have performed a serial study
      of pNfH levels in 98 subjects from our ALS clinic. There was significant
      elevation of levels of pNfH in subjects with ALS compared to controls, although
      there was considerable variability. In studies of individuals who had two or more
      serial samples, we found that the levels of pNfH increased over time in the early
      stage of disease. Levels were low in subjects with long survival. The rate of
      rise of pNfH was inversely correlated with survival. We suggest that the initial
      level of pNfH is a marker of disease severity and that changes in pNfH levels are
      markers of disease progression. 

PMID- 25958266
TI  - Nitric oxide ameliorates zinc oxide nanoparticles-induced phytotoxicity in rice
      seedlings.
AB  - Nitric oxide (NO) has been found to function in enhancing plant tolerance to
      various environmental stresses. However, role of NO in relieving zinc oxide
      nanoparticles (ZnO NPs)-induced phytotoxicity remains unknown. Here, sodium
      nitroprusside (SNP, a NO donor) was used to investigate the possible roles and
      the regulatory mechanisms of NO in counteracting ZnO NPs toxicity in rice
      seedlings. Our results showed that 10 MUM SNP significantly inhibited the
      appearance of ZnO NP toxicity symptoms. SNP addition significantly reduced Zn
      accumulation, reactive oxygen species production and lipid peroxidation caused by
      ZnO NPs. The protective role of SNP in reducing ZnO NPs-induced oxidative damage
      is closely related to NO-mediated antioxidant system. A decrease in superoxide
      dismutase activity, as well as an increase in reduced glutathione content and
      peroxidase, catalase and ascorbate peroxidase activity was observed under SNP and
      ZnO NPs combined treatments, compared to ZnO NPs treatment alone. The relative
      transcript abundance of corresponding antioxidant genes exhibited a similar
      change. The role of NO in enhancing ZnO NPs tolerance was further confirmed by
      genetic analysis using a NO excess mutant (noe1) and an OsNOA1-silenced plant
      (noa1) of rice. Together, this study provides the first evidence indicating that
      NO functions in ameliorating ZnO NPs-induced phytotoxicity.

PMID- 25958265
TI  - Positive correlation between care given by specialists and registered nurses and
      improved outcomes for stroke patients.
AB  - BACKGROUND: Cerebrovascular diseases are the second-highest cause of death in
      South Korea (9.6% of all causes of mortality in 2013). South Korea has a shortage
      of trained medical personnel compared with other countries and the demands for
      health care are continuously increasing. Our study sought to determine the
      relationship between hospital human resources and the outcomes of stroke
      patients. METHODS: We used data from NHI claims (n=99,464) at 120 hospitals to
      analyze readmission or death within 30 days after discharge or hospitalization
      for stroke patients during 2010-2013. We used multilevel models that included
      both patient-level and hospital-level variables to examine factors associated
      with readmission or death within 30 days. RESULTS: A total of 1782 (1.8%)
      patients were readmitted within 30 days, and death occurred within 30 days for
      6926 (7.0%) patients. Patients cared for by a higher percentages of specialists
      or registered nurses had a lower risk of readmission or death within 30 days
      (readmission per 10% increase in registered nurses, OR=0.89 and SD=0.85-0.94;
      death per 10% increase in specialists, OR=0.93 and SD=0.89-0.98). CONCLUSIONS:
      The percentages of specialist and registered nurses caring for stroke patients
      were positively correlated with better patient outcomes, particularly for
      patients with cerebral infarction.

PMID- 25958267
TI  - In vitro bioaccessibility of lead in surface dust and implications for human
      exposure: A comparative study between industrial area and urban district.
AB  - In this study, ground surface dust samples from two contrasting areas, a former
      zinc smelting area in Guizhou Province and a common urban district in Wuhan city,
      Hubei Province, China, were assessed for in vitro Pb bioaccessibility using a
      physiologically based extraction test (PBET). Extremely elevated concentrations
      of Pb (220-6348 mg/kg) and other trace metals were observed in the zinc smelting
      area. While moderate high metal concentrations (79-1544 mg/kg of Pb) in the urban
      dusts were attributed to various urban activities, coal combustion and traffic
      emissions. Lead bioaccessibility in the stomach-phase varied from 17.6 to 76.1%
      and no significant difference was found between industrial and urban dust
      samples. Compared with the stomach-phase, Pb bioaccessibility in the more
      alkaline intestinal-phase was considerably lower (1.2-21.8%). A significantly
      negative correlation was found between dust Ca concentrations and Pb
      bioaccessibility in the intestinal-phase, suggesting that Ca plays an important
      role in reducing the bioaccessible Pb in the intestinal-phase. The estimated Pb
      exposure based on gastric bioaccessible Pb was 13.9 and 1.8 MUg/kg day for
      children living in the industrial and urban areas, respectively, accounting for
      85% and 41% of their corresponding total Pb exposure.

PMID- 25958268
TI  - Molecular weight and galloylation affect grape seed extract constituents' ability
      to cross-link dentin collagen in clinically relevant time.
AB  - OBJECTIVE: To investigate the relationship between the structures of polyphenolic
      compounds found in grape seed extract (GSE) and their activity in cross-linking
      dentin collagen in clinically relevant settings. METHODS: Representative
      monomeric and dimeric GSE constituents including (+)-catechin (pCT), (-)-catechin
      (CT), (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate
      (ECG), (-)-epigallocatechin gallate (EGCG), procyanidin B2 and a pCT-pCT dimer
      were purchased or synthesized. GSE was separated into low (PALM) and high
      molecular weight (PAHM) fractions. Human molars were processed into dentin films
      and beams. After demineralization, 11 groups of films (n=5) were treated for 1min
      with the aforementioned reagents (1wt% in 50/50 ethanol/water) and 1 group
      remained untreated. The films were studied by Fourier transform infrared
      spectroscopy (FTIR) followed by a quantitative mass spectroscopy-based digestion
      assay. Tensile properties of demineralized dentin beams were evaluated (n=7)
      after treatments (2h and 24h) with selective GSE species that were found to
      protect dentin collagen from collagenase. RESULTS: Efficacy of GSE constituents
      in cross-linking dentin collagen was dependent on molecular size and
      galloylation. Non-galloylated species with degree of polymerization up to two,
      including pCT, CT, EC, EGC, procyanidin B2 and pCT-pCT dimer were not active.
      Galloylated species were active starting from monomeric form, including ECG,
      EGCG, PALM, GSE and PAHM. PALM induced the best overall improvement in tensile
      properties of dentin collagen. SIGNIFICANCE: Identification under clinically
      relevant settings of structural features that contribute to GSE constituents'
      efficacy in stabilizing demineralized dentin matrix has immediate impact on
      optimizing GSE's use in dentin bonding.

PMID- 25958270
TI  - WITHDRAWN: Hypercholesterolemia aggravates myocardial ischemia reperfusion injury
      via activating endoplasmic reticulum stress-mediated apoptosis.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 25958269
TI  - Fatigue failure of dentin-composite disks subjected to cyclic diametral
      compression.
AB  - OBJECTIVE: Our aim was to establish the relationship between cyclic loading and
      fatigue life of the dentin-composite interface using the newly developed disk in
      diametral compression tests. The results were then used to estimate the fatigue
      life of restored teeth under occlusal loading. METHODS: Disk specimens (5mm
      dia.*2mm thick) were prepared using bovine incisors and restored with either a
      methacrylate-based composite Z100TM with Adper Single Bond Plus (Z100) or
      silorane-based composite FiltekTM LS with LS System adhesive (LS). The dentin
      composite disks were tested under cyclic diametral compression to determine the
      number of cycles to failure (Nf) at three load levels (n=3 per group). Finite
      element analysis (FEA) was used to calculate the interfacial stresses (sigma)
      within the specimen, to establish the sigma vs. Nf curves, and those within a
      restored tooth under normal chewing forces (15N maximum). These were then used to
      estimate the lifetime of the restored tooth for the two restorative systems.
      RESULTS: The disks restored with LS had a higher fatigue resistance than those
      restored with Z100. The maximum interfacial stress in the restored tooth
      determined by FEA was ~0.5MPa. Based on the estimate of 300,000 cycles of chewing
      per year, the predicted lifetime under occlusal loading for teeth restored with
      LS and Z100 was 33 and 10 years, respectively. SIGNIFICANCE: The disk in cyclic
      diametral compression has been used successfully to provide fatigue data which
      allows the lifetime of composite-restored teeth under occlusal loading to be
      predicted using numerical simulation.

PMID- 25958273
TI  - Effects of corn silage particle size, supplemental hay, and forage-to-concentrate
      ratio on rumen pH, feed preference, and milk fat profile of dairy cattle.
AB  - Two experiments (Exp.) were conducted to study effects of feeding long or short
      corn silage total mixed rations (TMR) on rumen pH, feed preference, and dairy cow
      performance and to determine the rate of recovery from grain-induced subacute
      ruminal acidosis (SARA). Both experiments utilized a crossover design with 12
      lactating, multiparous, Holstein cows each (including 4 ruminally cannulated
      cows) and consisted of two 26-d periods. Each period consisted of 12d of
      adaptation followed by 14d of data collection. Each period was divided into 4
      phases: adaptation, d 1 to 12; baseline, d 13 to 14; challenge, d 15 to 19; and
      recovery, d 20 to 26. Treatments in Exp. 1 were TMR based on corn silage with
      long (L) or short (ST) particle size in a 65:35 forage-to-concentrate (F:C) diet.
      Treatments in Exp. 2 were TMR based on corn silage with short (SH) or long (LH)
      particle size in a 65:35 F:C diet with 3.3% (DM basis) orchardgrass hay offered
      as a supplement to the diet. In both experiments, during the challenge phase cows
      received a 50:50 F:C diet to initiate SARA. Animals were housed individually,
      milked twice per day, and fed once per day for 10% refusal rate on an as-fed
      basis. Data were analyzed using PROC MIXED of SAS. Feeding L and LH diets
      increased acetate-to-propionate ratio in the rumen, which resulted in the
      maintenance of a ratio >2 from the start of the SARA challenge through recovery.
      In Exp. 1, feeding long corn silage TMR resulted in lower milk fat concentration
      on the third day of the challenge, whereas cows fed short corn silage TMR had
      lower milk fat concentration on the final day of the challenge compared with d
      13. Providing supplemental hay to cows fed TMR based on long or short corn silage
      in Exp. 2 prevented acidosis when cows were challenged with a high-grain diet.
      Milk fat concentrations substantially decreased during the challenge phase in
      both diets supplemented with hay, but feeding LH did not lower milk fat
      concentrations until d 20 compared with d 17 for cows fed SH. Under the
      conditions of these experiments, cows selected for shorter particles compared
      with longer particles, despite the rumen challenge. However, when feeding a 50:50
      F:C diet, feeding long corn silage TMR or supplementing the diet with grass hay
      increased rumen pH, acetate-to-propionate ratio in the rumen, and rate of
      recovery from SARA. 

PMID- 25958274
TI  - Genetic parameters of cheese yield and curd nutrient recovery or whey loss traits
      predicted using Fourier-transform infrared spectroscopy of samples collected
      during milk recording on Holstein, Brown Swiss, and Simmental dairy cows.
AB  - Cheese yield is the most important technological parameter in the dairy industry
      in many countries. The aim of this study was to infer (co)variance components for
      cheese yields (CY) and nutrient recoveries in curd (REC) predicted using Fourier
      transform infrared (FTIR) spectroscopy of samples collected during milk recording
      on Holstein, Brown Swiss, and Simmental dairy cows. A total of 311,354 FTIR
      spectra representing the test-day records of 29,208 dairy cows (Holstein, Brown
      Swiss, and Simmental) from 654 herds, collected over a 3-yr period, were
      available for the study. The traits of interest for each cow consisted of 3
      cheese yield traits (%CY: fresh curd, curd total solids, and curd water as a
      percent of the weight of the processed milk), 4 curd nutrient recovery traits
      (REC: fat, protein, total solids, and the energy of the curd as a percent of the
      same nutrient in the processed milk), and 3 daily cheese production traits (daily
      fresh curd, total solids, and the water of the curd per cow). Calibration
      equations (freely available upon request to the corresponding author) were used
      to predict individual test-day observations for these traits. The (co)variance
      components were estimated for the CY, REC, milk production, and milk composition
      traits via a set of 4-trait analyses within each breed. All analyses were
      performed using REML and linear animal models. The heritabilities of the %CY were
      always higher for Holstein and Brown Swiss cows (0.22 to 0.33) compared with
      Simmental cows (0.14 to 0.18). In general, the fresh cheese yield (%CYCURD)
      showed genetic variation and heritability estimates that were slightly higher
      than those of its components, %CYSOLIDS and %CYWATER. The parameter RECPROTEIN
      was the most heritable trait in all the 3 breeds, with values ranging from 0.32
      to 0.41. Our estimation of the genetic relationships of the CY and REC with milk
      production and composition revealed that the current selection strategies used in
      dairy cattle are expected to exert only limited effects on the REC traits.
      Instead, breeders may be able to exploit genetic variations in the %CY,
      particularly RECFAT and RECPROTEIN. This last component is not explained by the
      milk protein content, suggesting that its direct selection could be beneficial
      for cheese production aptitude. Collectively, our findings indicate that breeding
      strategies aimed at enhancing CY and REC could be easily and rapidly implemented
      for dairy cattle populations in which FTIR spectra are routinely acquired from
      individual milk samples. 

PMID- 25958275
TI  - Short communication: Determination of withdrawal time for oxytetracycline in
      different types of goats for milk consumption.
AB  - Antibiotics are widely used in animal husbandry and the presence of antibiotics
      in milk is a health hazard. The objective of this study was to determine residual
      amounts of oxytetracycline in fresh, aged, and pasteurized milk of 3 breeds of
      goats using HPLC analysis. It was also essential to determine the safe withdrawal
      period of oxytetracycline in lactating goats. The quantitative results obtained
      using the HPLC system were compared with the tolerance limit of oxytetracycline
      in milk in the United States. Fifteen milking does, 5 Nubians, 5 Alpines, and 5
      LaManchas were randomly selected from the milking herd at the International Goat
      Research Center at Prairie View A&M University. A simple sample preparation and
      isocratic HPLC method using ultraviolet detection was used for analysis of milk
      samples. The HPLC results indicated that the withdrawal period of oxytetracycline
      in treated Alpine does was 82h (7 milking), whereas for Nubian does the period
      was 58h (5 milking), and for LaManchas the period was 72h (6 milking) after drug
      administration. The overall withdrawal period for all the treated goats of 3
      breeds was 72h. Although these results indicated that the depletion rate of this
      antibiotic was faster in goats than the reported data for cows, the 96-h
      withdrawal period that is currently used for lactating cows is still necessary
      for these 3 breeds of goats. Additionally, our results indicated that
      oxytetracycline is not stable in goat milk at refrigeration temperature or during
      pasteurization and will decrease significantly. 

PMID- 25958271
TI  - Evolution of two prototypic T cell lineages.
AB  - Jawless vertebrates, which occupy a unique position in chordate phylogeny, employ
      leucine-rich repeat (LRR)-based variable lymphocyte receptors (VLR) for antigen
      recognition. During the assembly of the VLR genes (VLRA, VLRB and VLRC), donor
      LRR-encoding sequences are copied in a step-wise manner into the incomplete germ
      line genes. The assembled VLR genes are differentially expressed by discrete
      lymphocyte lineages: VLRA- and VLRC-producing cells are T-cell like, whereas VLRB
      producing cells are B-cell like. VLRA(+) and VLRC(+) lymphocytes resemble the two
      principal T-cell lineages of jawed vertebrates that express the alphabeta or
      gammadelta T-cell receptors (TCR). Reminiscent of the interspersed nature of the
      TCRalpha/TCRdelta locus in jawed vertebrates, the close proximity of the VLRA and
      VLRC loci facilitates sharing of donor LRR sequences during VLRA and VLRC
      assembly. Here we discuss the insight these findings provide into vertebrate T-
      and B-cell evolution, and the alternative types of anticipatory receptors they
      use for adaptive immunity. 

PMID- 25958276
TI  - Effects of conditioning temperature and time during the pelleting process on feed
      molecular structure, pellet durability index, and metabolic features of co
      products from bio-oil processing in dairy cows.
AB  - The objectives of this study were to systematically determine effects of
      conditioning temperature (70, 80, and 90 degrees C), time (50 and 75 s), and
      interaction (temperature * time) during the pelleting process on co-products from
      bio-oil processing (canola meal) in terms of processing-induced changes on (1)
      protein molecular structure, (2) pellet durability index, (3) detailed chemical
      profile, (4) metabolic features and fractions of protein and carbohydrate, (5)
      total digestible nutrients and energy values, and (6) rumen degradable and
      undegradable content. Pellet durability was increased with increasing
      conditioning time. Chemical and carbohydrate profiles of co-products were not
      altered by pelleting process under different conditioning temperatures and times.
      With regard to protein fraction profiles, pellets conditioned for 50 s had higher
      soluble crude protein (SCP) and lower neutral detergent insoluble crude protein
      (NDICP) contents than those conditioned for 75 s (21.7 vs. 20.1% SCP, 16.0 vs.
      16.5% NDICP, respectively). Total digestible nutrients and energy values were not
      altered by processing. Samples conditioned for 50 s had a higher content of
      rapidly degradable protein fraction (PA2) than those conditioned for 75 s (21.7
      vs. 21.1% crude protein). In addition, the slowly degradable true protein
      fraction (PB2) was affected by the interaction of conditioning temperature and
      time. However, carbohydrate fractions did not differ with different conditioning
      temperatures and time. Different temperatures and time of conditioning during
      pelleting process greatly affect protein profiles without altering carbohydrate
      profiles. Molecular structure analyses also showed that pelleting altered
      inherent protein molecular structures of the co-products from bio-oil processing.
      Future study is needed to detect how molecular structure changes affect nutrient
      availability in dairy cattle. 

PMID- 25958272
TI  - All hands on DE(T)C: Epithelial-resident gammadelta T cells respond to tissue
      injury.
AB  - Immunology has traditionally focused on the lymphocytes circulating among primary
      lymphoid organs while the large reservoir of tissue-resident T cells have
      received relatively less attention. In epithelia, these populations are comprised
      of significant, and sometimes exclusive, subsets of gammadelta T cells that are
      highly specialized in promoting tissue homeostasis. As the epithelial layers of
      the skin and gut are permanently exposed to the environment, they are continually
      subject to injury and therefore require highly efficient repair processes to
      maintain barrier functions. Here, we review the role of gammadelta T cells in
      promoting wound healing, a critical and complex process occurring in the skin and
      other barrier sites. 

PMID- 25958277
TI  - Different management practices are associated with mesophilic and thermophilic
      spore levels in bulk tank raw milk.
AB  - Bacterial endospores (also referred to as spores) present in raw milk are capable
      of surviving pasteurization and other adverse conditions encountered during dairy
      powder production. Therefore, requiring low spore levels in raw ingredients
      (e.g., raw milk) may be necessary for producing dairy powders with low spore
      counts. To identify potential associations between management practices and spore
      levels in raw milk, we sampled bulk tank raw milk from 33 farms throughout New
      York State every other month for 1yr. Following spore pasteurization (80 degrees
      C for 12min), samples were incubated at 3 different temperatures to enumerate
      psychrotolerant (6 degrees C for 10 d), mesophilic (32 degrees C for 48h), and
      thermophilic (55 degrees C for 48h) spores. An additional enrichment procedure
      was used to detect spores present at low levels (<10 spores/mL). Overall,
      psychrotolerant, mesophilic, and thermophilic spores were detected (at levels
      >=10 spores/mL) in 1, 74, and 58% of bulk tank raw milk samples, respectively.
      Although thermophilic spore levels could not be quantified (due to bacterial
      swarming), mesophilic spore levels ranged from below detection (<10 spores/mL) to
      680 spores/mL. Data collected through surveys were used to identify management
      practices associated with either mesophilic or thermophilic spore levels. We
      found that different management practices are associated with mesophilic and
      thermophilic spore levels. Low mesophilic spore levels in bulk tank raw milk
      samples were associated with (1) large herd size, (2) use of sawdust or sand
      bedding, and (3) not fore stripping during the premilking routine. Management
      practices that were associated with lower odds of having a thermophilic spore
      level >=10 spores/mL are (1) large herd size, (2) spray-based application of the
      postmilking disinfectant, (3) dry massaging the udder during the premilking
      routine, and (4) the use of straw bedding. Collectively, these results suggest
      that different management practices may influence mesophilic and thermophilic
      spore levels in raw milk. 

PMID- 25958278
TI  - Microbiological quality of milk sold directly from producers to consumers.
AB  - The aim of this study was to determine the microbiological quality of raw cow
      milk from direct sale points. Raw cow milk samples were collected from 5 randomly
      selected direct sale points for microbiological evaluation. The samples were
      analyzed to determine total aerobic bacterial count, somatic cell count (SCC),
      counts of Enterobacteriaceae, Enterococcus, Escherichia coli, and Staphylococcus,
      and presence of Salmonella, Listeria monocytogenes, and inhibitory substances.
      The mean counts of total aerobic bacterial in samples from all direct sale points
      were between 9.2*10(4) and 3.6*10(7) cfu/mL. Milk samples collected from 5 direct
      sale points revealed counts Enterobacteriaceae ranging from 6.4*10(1) to
      1.7*10(6) cfu/mL. Escherichia coli were detected in 12 milk samples with counts
      ranging from 5.0*10(0) to 1.1*10(2) cfu/mL. Staphylococcus spp. bacteria were
      found in all milk samples, at counts ranging from 1.6*10(3) to 5.1*10(4) cfu/mL.
      Listeria monocytogenes bacteria were detected in 1 sample, and SCC in all samples
      ranged from 78,000 to 1,730,000/mL. The examined samples did not contain
      Salmonella rods or inhibitory substances. In the samples examined in this study,
      international hygiene standards were exceeded for total aerobic bacterial count
      (n=48) as well as for SCC (n=19). Two milk samples contained pathogenic bacteria
      (Listeria monocytogenes and Staphylococcus aureus) that pose a potential hazard
      for consumer health. 

PMID- 25958279
TI  - First-lactation performance in cows affected by digital dermatitis during the
      rearing period.
AB  - The long-term effects of prepartum digital dermatitis (DD) on first-lactation
      performance were evaluated in a cohort of 719 pregnant heifers. All heifers were
      followed for a period of 6 mo until calving and classified on the basis of the
      number of DD events diagnosed during this period as type I, type II, or type III
      (no DD, one DD event, and multiple DD events, respectively). Health during the
      initial 60d in milk (DIM), reproductive and hoof health outcomes, and milk
      production were compared between the 3 heifer type groups. All logistic and
      linear models were adjusted for age, height, and girth circumference at
      enrollment, and the type of trace mineral supplementation during the prepartum
      period. Overall, cows experiencing DD during the rearing period showed worse
      production and health outcomes compared with healthy heifers during the first
      lactation. The percentages of assisted calvings, stillbirths, culled before 60
      DIM, and diseased cows during the fresh period were numerically higher in type
      III cows compared with type I cows. However, none of these differences were
      statistically significant at the 95% confidence level. Significantly lower
      conception at first service [odds ratio (OR)=0.55, 95% confidence interval (95%
      CI): 0.33, 0.89] and increased number of days open (mean=24d, 95% CI: 5.2, 43)
      were observed in type III cows compared with type I cows. In relation to hoof
      health, a significantly increased risk of DD during the first lactation was found
      in type II and III cows (OR=5.16, 95% CI: 3.23, 8.29; and OR=12.5, 95% CI: 7.52,
      21.1, respectively), as well as earlier occurrence of DD following calving
      (OR=59d, 95% CI=20, 96, and OR=74d, 95% CI: 37, 109). Compared with type I cows,
      statistically significant milk production losses during the initial 305 DIM of
      199 and 335kg were estimated in type II and III cows, respectively. This
      difference was due to a greater rate of production decline (less persistence)
      after peak yield. No differences in monthly fat and protein percentages or
      somatic cell counts were observed between the heifer types. Given the long-term
      effects of DD on health, reproduction, and production, one of the priorities
      during the rearing period of dairy heifers should be efficient DD prevention and
      control programs. Such intensive intervention programs based on active long-term
      DD surveillance, mitigation of risk factors, and prompt treatment are expected to
      increase overall animal well-being and farm profitability by minimizing the
      effect of DD during the first lactation. 

PMID- 25958280
TI  - Rear shape in 3 dimensions summarized by principal component analysis is a good
      predictor of body condition score in Holstein dairy cows.
AB  - Body condition is an indirect estimation of the level of body reserves, and its
      variation reflects cumulative variation in energy balance. It interacts with
      reproductive and health performance, which are important to consider in dairy
      production but not easy to monitor. The commonly used body condition score (BCS)
      is time consuming, subjective, and not very sensitive. The aim was therefore to
      develop and validate a method assessing BCS with 3-dimensional (3D) surfaces of
      the cow's rear. A camera captured 3D shapes 2 m from the floor in a weigh station
      at the milking parlor exit. The BCS was scored by 3 experts on the same day as 3D
      imaging. Four anatomical landmarks had to be identified manually on each 3D
      surface to define a space centered on the cow's rear. A set of 57 3D surfaces
      from 56 Holstein dairy cows was selected to cover a large BCS range (from 0.5 to
      4.75 on a 0 to 5 scale) to calibrate 3D surfaces on BCS. After performing a
      principal component analysis on this data set, multiple linear regression was
      fitted on the coordinates of these surfaces in the principal components' space to
      assess BCS. The validation was performed on 2 external data sets: one with cows
      used for calibration, but at a different lactation stage, and one with cows not
      used for calibration. Additionally, 6 cows were scanned once and their surfaces
      processed 8 times each for repeatability and then these cows were scanned 8 times
      each the same day for reproducibility. The selected model showed perfect
      calibration and a good but weaker validation (root mean square error=0.31 for the
      data set with cows used for calibration; 0.32 for the data set with cows not used
      for calibration). Assessing BCS with 3D surfaces was 3 times more repeatable
      (standard error=0.075 versus 0.210 for BCS) and 2.8 times more reproducible than
      manually scored BCS (standard error=0.103 versus 0.280 for BCS). The prediction
      error was similar for both validation data sets, indicating that the method is
      not less efficient for cows not used for calibration. The major part of
      reproducibility error incorporates repeatability error. An automation of the
      anatomical landmarks identification is required, first to allow broadband
      measures of body condition and second to improve repeatability and consequently
      reproducibility. Assessing BCS using 3D imaging coupled with principal component
      analysis appears to be a very promising means of improving precision and
      feasibility of this trait measurement. 

PMID- 25958281
TI  - Incremental amounts of ground flaxseed decrease milk yield but increase n-3 fatty
      acids and conjugated linoleic acids in dairy cows fed high-forage diets(1).
AB  - The objective of this study was to investigate the effect of incremental amounts
      of ground flaxseed (GFX) on milk yield and concentrations and yields of milk
      components, milk fatty acids (FA) profile, ruminal metabolism, and nutrient
      digestibility in dairy cows fed high-forage diets. Twelve multiparous Jersey cows
      averaging (mean +/- SD) 112+/-68d in milk and 441+/-21kg of body weight and 8
      primiparous Jersey cows averaging 98+/-43d in milk and 401+/-43kg of body weight
      were randomly assigned to treatment sequences in a replicated 4*4 Latin square
      design. Each period lasted 21d with 14d for diet adaptation and 7d for data and
      sample collection. Treatments were fed as a total mixed ration (63:37 forage-to
      concentrate ratio) with corn meal and soybean meal replaced by incremental levels
      (i.e., 0, 5, 10, or 15% diet dry matter) of GFX. The ruminal molar proportions of
      acetate and butyrate decreased linearly with GFX supplementation, whereas the
      ruminal molar proportion of propionate increased linearly resulting in decreased
      acetate-to-propionate ratio. Apparent total-tract digestibilities of nutrients
      either decreased (dry matter) or tended to decrease (organic matter, neutral
      detergent fiber, acid detergent fiber) linearly in cows fed GFX. Milk yield
      decreased linearly in cows fed increasing amounts of GFX, which is explained by
      the linear reduction in dry matter intake. Except for the concentrations of milk
      protein and urea N, which decreased linearly with GFX supplementation, no other
      changes in the concentration of milk components were observed. However, yields of
      milk protein and fat decreased linearly with GFX supplementation. The linear
      decrease in the yields of milk fat and protein are explained by reduced milk
      yield, whereas that in milk urea N is explained by decreased crude protein
      intake. No treatment effects were observed for plasma urea N and nonesterified
      fatty acids, serum cortisol, and body weight change. Milk odd- and branched-chain
      FA and saturated FA decreased linearly with GFX supplementation. Milk trans-11
      18:1, alpha-linolenic acid, cis-9,trans-11 18:2, and the sum of n-3 FA all
      increased linearly and quadratically, whereas the milk ratio of n-6 to n-3
      decreased linearly in cows fed GFX. Overall, compared with the control diet (0%
      GFX), the diet with 15% GFX supplementation resulted in the lowest milk yield but
      highest milk proportions and yields (data not shown) of cis-9,trans-11 18:2 and n
      3 FA. 

PMID- 25958282
TI  - Using a family-based structure to detect the effects of genomic inbreeding on
      embryo viability in Holstein cattle.
AB  - Recent evidence has suggested that some of the decline in reproductive ability in
      dairy cattle has been caused by embryonic death. The current study compared
      expected genomic inbreeding from sire-dam mating pairs to genomic inbreeding from
      live progeny in an attempt to determine how embryonic inbreeding may affect
      fertility. A total of 11,484 Holstein cattle with 43,485 SNP markers and pedigree
      information were available for analysis. A total of 412 sire-dam-progeny trios in
      which all animals had reliable genotypes were discovered. After removal of trios
      because of parentage errors, 374 remained for analysis. Additionally, a total of
      3,031 animals comprising 3,906 genotyped full-sibling pairs were available for
      comparison. Expected genomic inbreeding measures were calculated by predicting
      homozygosity independently per SNP (FPHE) in sire-dam mating pairs and by
      simulating progeny using phased haplotype information (FROHE and FPHE). Actual
      genomic inbreeding measures were calculated using the percent homozygosity of all
      SNP (FPH) and using runs of homozygosity (FROH). Average FPHE values (62.8+/
      0.78%) were slightly lower than FPH (63.1+/-1.12%), when considering each SNP
      independently. After phasing haplotypes, FPHE (62.5+/-0.83%) was again slightly
      lower than FPH (62.7+/-1.16%), and FROHE (3.46+/-1.54%) was slightly lower than
      FROH (3.53+/-2.17%). Results suggest increases in expected genomic inbreeding do
      not explain a large effect on embryo viability at average levels of expected
      inbreeding. Higher variation in FROH values was present with sire-dam mating
      pairs exhibiting high FROHE, which may suggest high levels of genomic inbreeding
      are required for a noticeable effect on overall embryo viability. Genomic
      inbreeding between full siblings was also compared with moderate correlations
      (0.47-0.52) present. Overall, expected genomic inbreeding measures were
      calculated, but results did not suggest a large effect of expected inbreeding on
      embryo viability. 

PMID- 25958283
TI  - Relationship of concentrations of cortisol in hair with health, biomarkers in
      blood, and reproductive status in dairy cows.
AB  - Hair cortisol has been used to measure chronic stress in dairy cows as it offers
      the advantage of being noninvasive, fast, and able to indicate levels of cortisol
      over long periods. The aim of this study was to determine the associations
      between hair cortisol with clinical disorders, reproductive status, and the
      development of subclinical endometritis in dairy cows. Furthermore, we aimed to
      determine the association between hair cortisol concentrations and blood markers
      associated with metabolic status and acute inflammation. In experiment 1, cows
      (n=64) were hair sampled every 3wk from the tail switch beginning at calving (d
      0) until d 126 for cortisol analysis; blood samples were collected every 3wk from
      d 0 until 42 for beta-hydroxybutyrate and glucose analysis. In experiment 2, cows
      (n=54) were chosen retrospectively by diagnosis of subclinical endometritis
      (END), subclinical endometritis and at least 1 clinical disease (END+CLIN), or as
      healthy (control) using a cytobrush and ultrasonography at 30+/-3d in milk. At
      the same time, animals were hair sampled for cortisol analysis and blood sampled
      for haptoglobin and ceruloplasmin analysis. Health records were recorded
      throughout both experimental periods. Animals with clinical disease presented
      higher cortisol concentrations than clinically healthy animals in experiment 1
      [geometric mean (95% confidence interval); 8.8 (7.8, 9.9) vs. 10.7 (9.6, 12.0)
      pg/mg]; however, animals diagnosed with subclinical endometritis in experiment 2
      did not differ in hair cortisol concentrations [11.7 (9.8, 14.0), 12.2 (9.3,
      15.9), 10.5 (8.1, 13.6) pg/mg for control, END, and END+CLIN, respectively]. In
      experiment 1, an effect of sample day was noted, where d 21 had higher cortisol
      concentrations than d 42, 84, and 126, but not from d 0 for both parities. Within
      both experiments, a parity effect was present where multiparous animals
      consistently had higher cortisol concentrations than primiparous animals.
      Multiparous cows that became pregnant by 100d postpartum had lower concentrations
      of hair cortisol at d 42 and 84 in milk. Lastly, other biomarkers associated with
      metabolic status and acute inflammation, such as glucose, beta-hydroxybutyrate,
      haptoglobin, and ceruloplasmin, were not strongly correlated with measurements of
      cortisol in hair. Overall, hair cortisol measurements appear to be associated
      with clinical disorders and have a direct association with pregnancy status;
      however, concentrations of hair cortisol may not be suited to differentiate
      situations of stress with lower magnitudes, such as the development of
      subclinical disease. 

PMID- 25958284
TI  - Properties of acid whey as a function of pH and temperature.
AB  - Compositional differences of acid whey (AW) in comparison with other whey types
      limit its processability and application of conventional membrane processing.
      Hence, the present study aimed to identify chemical and physical properties of AW
      solutions as a function of pH (3 to 10.5) at 4 different temperatures (15, 25,
      40, or 90 degrees C) to propose appropriate membrane-processing conditions for
      efficient use of AW streams. The concentration of minerals, mainly calcium and
      phosphate, and proteins in centrifuged supernatants was significantly lowered
      with increase in either pH or temperature. Lactic acid content decreased with pH
      decline and rose at higher temperatures. Calcium appeared to form complexes with
      phosphates and lactates mainly, which in turn may have induced molecular
      attractions with the proteins. An increase in pH led to more soluble protein
      aggregates with large particle sizes. Surface hydrophobicity of these particles
      increased significantly with temperature up to 40 degrees C and decreased with
      further heating to 90 degrees C. Surface charge was clearly pH dependent. High
      lactic acid concentrations appeared to hinder protein aggregation by hydrophobic
      interactions and may also indirectly influence protein denaturation. Processing
      conditions such as pH and temperature need to be optimized to manipulate
      composition, state, and surface characteristics of components of AW systems to
      achieve an efficient separation and concentration of lactic acid and lactose. 

PMID- 25958285
TI  - Using wireless rumen sensors for evaluating the effects of diet and ambient
      temperature in nonlactating dairy goats.
AB  - Sixteen Murciano-Granadina dairy goats, provided with wireless rumen sensors for
      pH and temperature, were used to assess the rumen environment variations produced
      by extreme forage to concentrate diets (experiment 1) and climatic conditions
      (experiment 2). To avoid the interference of feed intake, goats were fed at
      maintenance level. Rumen sensors were inserted by surgery and programmed to
      collect and store rumen pH and temperature every 30min. In experiment 1, 8 dry
      goats (38.6+/-2.3kg of body weight) in tiestalls were divided into 2 groups and
      fed at maintenance level with 2 diets varying in forage-to-concentrate ratio
      [high forage (HF) 70:30; low forage (LF) 30:70] according to a crossover design.
      Diets were offered once daily for 4h and tap water (4 L, 9.8+/-0.4 degrees C) was
      offered for only 30min at 6h after feeding. Rectal temperatures were recorded 3
      times during the day. Rumen pH fell immediately after feeding, reaching a nadir
      depending on the diet (HF=6.35+/-0.07 at 11h after feeding; LF=6.07+/-0.07 at 6h
      after feeding) and being on average greater (0.31+/-0.06) in HF than LF goats. No
      diet effects were detected in rectal (38.2+/-0.1 degrees C) and ruminal (38.9+/
      0.1 degrees C) mean temperatures, which were positively correlated. Rumen
      temperature dramatically changed by feeding (1.4+/-0.1 degrees C) and drinking (
      3.4+/-0.1 degrees C), and 2h were necessary to return to the fasting value
      (38.2+/-0.1 degrees C). In experiment 2, 8 dry goats (43.9+/-1.0kg of body
      weight) were kept in metabolic cages, fed a 50:50 diet and exposed to 2 climatic
      conditions following a crossover design. Conditions were thermoneutral (TN; 20 to
      23 degrees C day-night) and heat stress (HS; 12-h day at 37 degrees C and 12-h
      night at 30 degrees C). Humidity (40+/-5%) and photoperiod (light-dark, 12-12h)
      were similar. Goats were fed at maintenance level, the feed being offered once
      daily and water at ambient temperature was freely available. Intake, rectal
      temperature, and respiratory rate were recorded 3 times daily. Despite no
      differing in dry matter intake, rumen pH was lower in HS than in TN goats (
      0.12+/-0.04). On the contrary, rumen temperature (0.3+/-0.1 degrees C), rectal
      temperature (0.4+/-0.1 degrees C), respiratory rate (77+/-5 breaths/min), and
      water intake (3.2+/-0.7 L/d) had a greater increase in HS than TN, which might
      indicate an altered microbial fermentation under high temperature conditions. In
      conclusion, wireless bolus sensors proved to be a useful tool to monitor rumen pH
      and temperature as affected by different feeding and climatic conditions. 

PMID- 25958286
TI  - Kinetic and thermodynamic parameters for thermal denaturation of ovine milk
      lactoferrin determined by its loss of immunoreactivity.
AB  - Lactoferrin is a protein with important biological functions that can be obtained
      from milk and by-products derived from the dairy industry, such as whey. Although
      bovine lactoferrin has been extensively studied, ovine lactoferrin is not quite
      as well known. In the present study, the effect of several heat treatments in 3
      different media, over a temperature range from 66 to 75 degrees C, has been
      studied on lactoferrin isolated from sheep milk. Denaturation of lactoferrin was
      determined by measuring its immunoreactivity with specific polyclonal antibodies.
      Kinetic and thermodynamic parameters obtained indicate that lactoferrin denatures
      by heat more rapidly in whey than in phosphate buffer or milk. The value of
      activation energy found for the denaturation process of lactoferrin when treated
      in whey is higher (390kJ/mol) than that obtained in milk (194kJ/mol) or phosphate
      buffer (179kJ/mol). This indicates that a great amount of energy is necessary to
      start denaturation of ovine lactoferrin, probably due to the interaction of this
      protein with other whey proteins. The changes in the hydrophobicity of
      lactoferrin after heat treatments were determined by fluorescence measurement
      using acrylamide. The decrease in the hydrophobicity constant was very small for
      the treatments from 66 to 75 degrees C, up to 20min, which indicates that
      lactoferrin conformation did not experienced a great change. The results obtained
      in this study permit the prediction of behavior of ovine lactoferrin under
      several heat treatments and show that high-temperature, short-time pasteurization
      (72 degrees C, 15 s) does not cause loss of its immunoreactivity and,
      consequently, would not affect its conformation and biological activity. 

PMID- 25958287
TI  - The effect of heat waves on dairy cow mortality.
AB  - This study investigated the mortality of dairy cows during heat waves. Mortality
      data (46,610 cases) referred to dairy cows older than 24mo that died on a farm
      from all causes from May 1 to September 30 during a 6-yr period (2002-2007).
      Weather data were obtained from 12 weather stations located in different areas of
      Italy. Heat waves were defined for each weather station as a period of at least 3
      consecutive days, from May 1 to September 30 (2002-2007), when the daily maximum
      temperature exceeded the 90th percentile of the reference distribution (1971
      2000). Summer days were classified as days in heat wave (HW) or not in heat wave
      (nHW). Days in HW were numbered to evaluate the relationship between mortality
      and length of the wave. Finally, the first 3 nHW days after the end of a heat
      wave were also considered to account for potential prolonged effects. The
      mortality risk was evaluated using a case-crossover design. A conditional
      logistic regression model was used to calculate odds ratio and 95% confidence
      interval for mortality recorded in HW compared with that recorded in nHW days
      pooled and stratified by duration of exposure, age of cows, and month of
      occurrence. Dairy cows mortality was greater during HW compared with nHW days.
      Furthermore, compared with nHW days, the risk of mortality continued to be higher
      during the 3 d after the end of HW. Mortality increased with the length of the
      HW. Considering deaths stratified by age, cows up to 28mo were not affected by
      HW, whereas all the other age categories of older cows (29-60, 61-96, and >96mo)
      showed a greater mortality when exposed to HW. The risk of death during HW was
      higher in early summer months. In particular, the highest risk of mortality was
      observed during June HW. Present results strongly support the implementation of
      adaptation strategies which may limit heat stress-related impairment of animal
      welfare and economic losses in dairy cow farm during HW. 

PMID- 25958288
TI  - Genetic analysis of heat stress effects on yield traits, udder health, and fatty
      acids of Walloon Holstein cows.
AB  - Genetic parameters that considered tolerance for heat stress were estimated for
      production, udder health, and milk composition traits. Data included 202,733 test
      day records for milk, fat, and protein yields, fat and protein percentages,
      somatic cell score (SCS), 10 individual milk fatty acids (FA) predicted by mid
      infrared spectrometry, and 7 FA groups. Data were from 34,468 first-lactation
      Holstein cows in 862 herds in the Walloon region of Belgium and were collected
      between 2007 and 2010. Test-day records were merged with daily temperature
      humidity index (THI) values based on meteorological records from public weather
      stations. The maximum distance between each farm and its corresponding weather
      station was 21km. Linear reaction norm models were used to estimate the intercept
      and slope responses of 23 traits to increasing THI values. Most yield and FA
      traits had phenotypic and genetic declines as THI increased, whereas SCS, C18:0,
      C18:1 cis-9, and 4 FA groups (unsaturated FA, monounsaturated FA, polyunsaturated
      FA, and long-chain FA) increased with THI. Moreover, the latter traits had the
      largest slope-to-intercept genetic variance ratios, which indicate that they are
      more affected by heat stress at high THI levels. Estimates of genetic
      correlations within trait between cold and hot environments were generally high
      (>0.80). However, lower estimates (<=0.67) were found for SCS, fat yield, and
      C18:1 cis-9, indicating that animals with the highest genetic merit for those
      traits in cold environments do not necessarily have the highest genetic merit for
      the same traits in hot environments. Among all traits, C18:1 cis-9 was the most
      sensitive to heat stress. As this trait is known to reflect body reserve
      mobilization, using its variations under hot conditions could be a very
      affordable milk biomarker of heat stress for dairy cattle expressing the
      equilibrium between intake and mobilization under warm conditions. 

PMID- 25958289
TI  - Insulin response of the glucose and fatty acid metabolism in dry dairy cows
      across a range of body condition scores.
AB  - The objective of the present research was to determine the insulin response of
      the glucose and fatty acid metabolism in dry dairy cows with a variable body
      condition score (BCS). Ten pregnant Holstein Friesian dairy cows (upcoming parity
      2 to 5) were selected based on BCS at the beginning of the study (2mo before
      expected parturition date). During the study, animals were monitored weekly for
      BCS and backfat thickness and in the last 2wk, blood samples were taken for
      determination of serum nonesterified fatty acid (NEFA) concentration. Animals
      underwent a hyperinsulinemic euglycemic clamp test in the third week before the
      expected parturition date. The hyperinsulinemic euglycemic clamp test consisted
      of 4 consecutive insulin infusions with increasing insulin doses: 0.1, 0.5, 2,
      and 5mIU/kg per minute. For each insulin infusion period, a steady state was
      defined as a period of 30min where no or minor changes of the glucose infusion
      were necessary to keep the blood glucose concentration constant and near basal
      levels. During the steady state, the glucose infusion rate [steady state glucose
      infusion rate (SSGIR) in umol/kg per minute] and NEFA concentration [steady state
      NEFA concentration (SSNEFA) in mmol/L] were determined and reflect the insulin
      response of the glucose and fatty acid metabolism. Dose response curves were
      created based on the insulin concentrations during the steady state and the SSGIR
      or SSNEFA. The shape of the dose response curves is determined by the
      concentration of insulin needed to elicit the half maximal effect (EC50) and the
      maximal SSGIR or the minimal SSNEFA for the glucose or fatty acid metabolism,
      respectively. The maximal SSGIR was negatively associated with variables
      reflecting adiposity of the cows (BCS, backfat thickness, NEFA concentration
      during the dry period, and absolute weight of the different adipose depots
      determined after euthanasia and dissection of the different depots), whereas the
      EC50 of the glucose metabolism was positively associated with these variables.
      These results reflect a decreased insulin sensitivity and a decreased insulin
      responsiveness of the glucose metabolism in overconditioned dry dairy cows. The
      minimal SSNEFA and the EC50 of the fatty acid metabolism were not associated with
      variables reflecting adiposity of the cows, meaning that the insulin response of
      the fatty acid metabolism was not associated with the level of fat accumulation
      in dry dairy cows. Additionally, within individual cows, the EC50 of the glucose
      metabolism was higher than the EC50 of the fatty acid metabolism, meaning that
      the response of the fatty acid metabolism occurs at lower insulin concentrations
      compared with the response of the glucose metabolism. It can be concluded that a
      negative association exists between the level of fat accumulation in pregnant
      dairy cows at the end of the dry period and the insulin response of the glucose
      metabolism. 

PMID- 25958290
TI  - Effect of including canola meal and supplemental iodine in diets of dairy cows on
      short-term changes in iodine concentrations in milk.
AB  - The dietary requirement for iodine is based on thyroxine production, but data are
      becoming available showing potential improvements in hoof health when
      substantially greater amounts of I are fed. Feeding high amounts of I, however,
      can result in the milk having excessive concentrations of I. Canola meal contains
      goitrogenic compounds that reduce the transfer of I into milk. We hypothesized
      that including canola meal in diets would allow high supplementation rates of I
      without producing milk with unacceptable concentrations of I. Thirty midlactation
      Holstein cows were fed a diet with all supplemental protein from soybean meal (0%
      of diet dry matter as canola meal) or with all supplemental protein from canola
      meal (13.9% canola meal). A third treatment has a mix of soybean meal and canola
      meal (3.9% canola meal). Within canola-meal treatment, cows were fed 0.5 or 2.0mg
      of supplemental I per kilogram of diet dry matter from ethylenediamine
      dihydroiodide. Cows were maintained on the canola treatment for the duration of
      the experiment but were changed from one I treatment to the other after 13d of
      receiving the treatment. Milk I concentration before the treatments started (cows
      fed 0.5mg/kg of I) averaged 272MUg/L and increased within 22h after cows were
      first fed diets with 2mg/kg of I. As inclusion rate of canola meal increased, the
      concentration of I in milk decreased linearly. After 12d of supplementation, milk
      from cows fed 0.5mg/kg of I had 358, 289, and 169MUg of I/L for the 0, 3.9%, and
      13.9% canola-meal treatments. For cows fed 2.0mg/kg of I, milk I concentrations
      were 733, 524, and 408MUg/L, respectively. Concentrations of I in serum increased
      with increased I supplementation, but the effect of canola meal was opposite of
      what was observed for milk I. Cows fed the highest canola-meal diets had the
      highest serum I whether cows were fed 0.5 or 2.0mg/kg of I. Feeding dairy cows
      diets with 13.9% canola meal maintained milk I concentrations below 500MUg/L when
      diets were supplemented with 2mg/kg of I. 

PMID- 25958291
TI  - Postruminal synthesis modifies the odd- and branched-chain fatty acid profile
      from the duodenum to milk.
AB  - Milk odd- and branched-chain fatty acids (OBCFA) have been suggested as potential
      biomarkers for rumen function. The potential of milk OBCFA as a biomarker depends
      on whether their profile reflects the profile observed in the duodenum. The
      objective of this study was to evaluate whether the OBCFA profile in duodenum
      samples is reflected in plasma and milk. For this, 2 dairy cattle experiments
      were used. In experiment 1, 4 Holstein cows fitted with rumen and proximal
      duodenum cannulas were used in a 4*4 Latin square design. The treatments
      consisted of 2 nitrogen levels (143 vs. 110g of crude protein/kg of dry matter
      for high and low N, respectively) combined with either 1 of the 2 energy sources
      (i.e., starch from barley, corn, and wheat or fiber from soybean hulls and
      dehydrated beet pulp). In experiment 2, 4 Holstein cows fitted with rumen and
      proximal duodenum cannulas were used in a 3*3 Latin square design, with the
      treatments consisting of 3 diets: (1) RNB-, a diet with a crude protein content
      of 122g/kg of dry matter, predicted to provide protein digested in the small
      intestine according to the requirement of the animals, but with a shortage of
      rumen degradable protein; (2) RNB- to which 6g/d of niacin was added through
      inclusion in the mineral and vitamin premix, and (3) RNB- to which urea was added
      to balance rumen degradable N supply resulting in a CP content of 156g/kg of dry
      matter. In both experiments, samples of duodenal digesta, plasma, and milk were
      collected and analyzed for fatty acids. Additionally, lipids in plasma samples
      were separated in lipid classes and analyzed for fatty acids. The OBCFA profile
      in milk was enriched in 15:0, iso-17:0, anteiso-17:0, and cis-9-17:1 as compared
      with duodenal samples, and milk secretions even exceeded duodenal flows, which
      suggests occurrence of postruminal synthesis, such as de novo synthesis,
      desaturation, and elongation. The postruminal modification of the OBCFA profile
      might hamper the application of OBCFA as diagnostic tools of rumen function. 

PMID- 25958292
TI  - Short- and long-term effects of forage supplementation of calves during the
      preweaning period on performance, reproduction, and milk yield at first
      lactation.
AB  - Sixty female Holstein calves [body weight (BW)=39.5+/-3.76kg] were fed a ground
      starter concentrate [19% crude protein, 19% neutral detergent fiber (NDF)] during
      the preweaning period. Furthermore, oats hay (68% NDF) was supplemented only
      during the postweaning period (CON) or during both pre- and postweaning periods
      (OH) to evaluate performance until first breeding, diet digestibility after
      weaning, reproductive performance, and milk yield at first lactation. Calves were
      individually housed and bedded with wood shavings. All calves were offered 6 L/d
      of milk replacer (MR) at 12% dry matter (DM) in 2 feedings until 28d of age, 3
      L/d of MR at 12% DM in 2 feedings from 29 to 44d of age calves, and 1.5 L of MR
      at 12% DM in 1 feeding from 45 to 51d of age. Animals were weaned at 52d of age.
      Starter concentrate and forage intake were recorded daily and BW weekly until 65d
      of age. Two weeks after weaning, total-tract apparent digestibility was
      determined in 6 calves per treatment. Heifer BW was recorded at 10 mo of age.
      Breeding and milk yield at first lactation were also recorded. Starter
      concentrate intake was greater in OH compared with CON animals during the
      preweaning period. As a result, calves in the OH treatment had greater average
      daily gain (ADG) than CON animals during the preweaning period. After weaning, OH
      calves consumed more forage than CON animals, but we found no differences between
      treatments in ADG and starter concentrate intake. Similarly, total-tract apparent
      digestibility did not differ between treatments, and BW and ADG from 2wk after
      weaning to 10mo of age did not differ between treatments. Moreover, no
      differences in reproductive performance [age at first artificial insemination
      (AI), age at fertile insemination, conception rate at first AI, and number of AI]
      or milk yield at first lactation were observed between treatments, although a
      positive relationship between growth rate early in life and future energy
      corrected milk yield was found. We conclude that offering forage to young calves
      early in life allows improvements in growth before weaning and could help in the
      transition to mixed diets, but the improvement in growth achieved early in life
      was not maintained at 10mo of age. 

PMID- 25958293
TI  - Strategies for single nucleotide polymorphism (SNP) genotyping to enhance
      genotype imputation in Gyr (Bos indicus) dairy cattle: Comparison of commercially
      available SNP chips.
AB  - Genotype imputation is widely used as a cost-effective strategy in genomic
      evaluation of cattle. Key determinants of imputation accuracies, such as linkage
      disequilibrium patterns, marker densities, and ascertainment bias, differ between
      Bos indicus and Bos taurus breeds. Consequently, there is a need to investigate
      effectiveness of genotype imputation in indicine breeds. Thus, the objective of
      the study was to investigate strategies and factors affecting the accuracy of
      genotype imputation in Gyr (Bos indicus) dairy cattle. Four imputation scenarios
      were studied using 471 sires and 1,644 dams genotyped on Illumina BovineHD (HD
      777K; San Diego, CA) and BovineSNP50 (50K) chips, respectively. Scenarios were
      based on which reference high-density single nucleotide polymorphism (SNP) panel
      (HDP) should be adopted [HD-777K, 50K, and GeneSeek GGP-75Ki (Lincoln, NE)].
      Depending on the scenario, validation animals had their genotypes masked for one
      of the lower-density panels: Illumina (3K, 7K, and 50K) and GeneSeek (SGGP-20Ki
      and GGP-75Ki). We randomly selected 171 sires as reference and 300 as validation
      for all the scenarios. Additionally, all sires were used as reference and the
      1,644 dams were imputed for validation. Genotypes of 98 individuals with 4 and
      more offspring were completely masked and imputed. Imputation algorithms FImpute
      and Beagle v3.3 and v4 were used. Imputation accuracies were measured using the
      correlation and allelic correct rate. FImpute resulted in highest accuracies,
      whereas Beagle 3.3 gave the least-accurate imputations. Accuracies evaluated as
      correlation (allelic correct rate) ranged from 0.910 (0.942) to 0.961 (0.974)
      using 50K as HDP and with 3K (7K) as low-density panels. With GGP-75Ki as HDP,
      accuracies were moderate for 3K, 7K, and 50K, but high for SGGP-20Ki. The use of
      HD-777K as HDP resulted in accuracies of 0.888 (3K), 0.941 (7K), 0.980 (SGGP
      20Ki), 0.982 (50K), and 0.993 (GGP-75Ki). Ungenotyped individuals were imputed
      with an average accuracy of 0.970. The average top 5 kinship coefficients between
      reference and imputed individuals was a strong predictor of imputation accuracy.
      FImpute was faster and used less memory than Beagle v4. Beagle v4 outperformed
      Beagle v3.3 in accuracy and speed of computation. A genotyping strategy that uses
      the HD-777K SNP chip as a reference panel and SGGP-20Ki as the lower-density SNP
      panel should be adopted as accuracy was high and similar to that of the 50K.
      However, the effect of using imputed HD-777K genotypes from the SGGP-20Ki on
      genomic evaluation is yet to be studied. 

PMID- 25958294
TI  - Outcomes of Cord Blood Transplantation Using Reduced-Intensity Conditioning for
      Chronic Lymphocytic Leukemia: A Study on Behalf of Eurocord and Cord Blood
      Committee of Cellular Therapy and Immunobiology Working Party, Chronic
      Malignancies Working Party of the European Society for Blood and Marrow
      Transplantation, and the Societe Francaise de Greffe de Moelle et Therapie
      Cellulaire.
AB  - Outcomes after umbilical cord blood transplantation (UCBT) for chronic
      lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) are unknown. We
      analyzed outcomes of 68 patients with poor-risk CLL/SLL who underwent reduced
      intensity (RIC) UCBT from 2004 to 2012. The median age was 57 years and median
      follow-up 36 months; 17 patients had del 17p/p53mutation, 19 patients had
      fludarabine-refractory disease, 11 relapsed after autologous stem cell
      transplantation, 8 had diagnosis of prolymphocytic leukemia, 4 had Richter
      syndrome, and 8 underwent transplantation with progressive or refractory disease.
      The most common RIC used was cyclophosphamide, fludarabine, and total body
      irradiation (TBI) in 82%; 15 patients received antithymocyte globulin. Most of
      the cord blood grafts were HLA mismatched and 76% received a double UCBT. Median
      total nucleated cells collected was 4.7 * 10(7)/kg. The cumulative incidences
      (CI) of neutrophil and platelet engraftment were 84% and 72% at 60 and 180 days
      respectively; day 100 graft-versus-host disease (GVHD) (grade II to IV) was 43%
      and 3-year chronic GVHD was 32%. The CI of relapse, nonrelapse mortality, overall
      survival, and progression-free survival (PFS) at 3 years were 16%, 39%, 54%, and
      45%, respectively. Fludarabine-sensitive disease at transplantation and use of
      low-dose TBI regimens were associated with acceptable PFS. In conclusion, use of
      RIC-UCBT seems to be feasible in patients with poor-risk CLL/SLL and improved
      outcomes were observed in patients with fludarabine-sensitive disease who
      received low-dose TBI regimens.

PMID- 25958295
TI  - Metastasising pleomorphic adenoma: Systematic review.
AB  - BACKGROUND: Pleomorphic adenoma (PA) is the commonest benign neoplasm of salivary
      glands.(1) PA can undergo malignant transformation to ex-pleomorphic adenoma
      (2,3) but rarely, can metastasise without malignant transformation.(4,5)
      Metastasising pleomorphic adenoma (MPA) is a rare malignant tumour which,
      histologically, is indistinguishable from PA yet produces secondary tumours in
      distant sites.(6,7,8) OBJECTIVE: Our aim is to review the literature for all
      reported cases of MPA and create a virtual series. The age and location of
      primary tumour with the location and time to metastasise will be reviewed. The
      prognosis and treatment options will be explored. METHOD: We conducted a PUBMED
      search with a combination of keywords: metastasizing/metastasising AND
      pleomorphic adenoma OR mixed tumour. An author's own case has also been included.
      RESULTS: Between 1942 and 2014 there were 80 case reports included in the review,
      plus the authors own case. Mean age at diagnosis of MPA was 49.5 years (range 11
      83). Male-to-female ratio was 34:46. The mean time between PA and MPA was 14.9
      years (range 0-51), with three cases reporting simultaneous presentation. 72.8%
      (n = 59) of cases reported PA local recurrence prior to MPA. The three most
      common sites for MPA were: bone 36.6% (n = 28), lung 33.8% (n = 26) and neck
      lymph nodes 20.1% (n = 17). Survival was poorly reported, but 41 (80.4%) were
      alive at 1-year. CONCLUSION: Benign MPA is rare. Metastasis occurs years after
      the initial PA and is associated with multiple local recurrences. Histologically,
      MPA retain their benign nature yet demonstrate malignant behaviour.

PMID- 25958297
TI  - Bevacizumab-based neoadjuvant chemotherapy for colorectal cancer liver
      metastases: Pitfalls and helpful tricks in a review for clinicians.
AB  - Bevacizumab added to chemotherapy has shown encouraging efficacy in the
      neoadjuvant therapy of colorectal cancer liver metastases. In absence of
      biological predictor factors of efficacy to bevacizumab-based treatment, the
      assessment of response may be a crucial point to select patients who may benefit
      the most from surgery. At the same time the pathological response after liver
      resection could represent a guide for the next therapeutic plan. In the pre
      surgical phase, conventional computed tomography and response evaluation with
      RECIST criteria may underestimate the response to anti-angiogenic drugs. Modified
      computed tomography criteria of response, morphologic changes as well as novel
      imaging techniques and metabolic assessment by fluorodeoxyglucose positron
      emission tomography seem to be promising methods for the assessment of response
      and for leading the clinical choices. Pathological response at the time of
      surgery is an important prognostic factor and a surrogate of survival for
      resected patients. Different classification criteria to assess pathological
      response have been developed, residual viable tumor, tumor regression grade
      (TRG), modified TRG and tumor thickness at the tumor-normal interface, but to
      date a superiority of one approach over the others has not been clearly
      established. In this review, we evaluate the available data with the aim to help
      the clinicians in the pre- and post-surgical care of patient with colorectal
      cancer liver metastases treated with bevacizumab-based neoadjuvant strategy. 

PMID- 25958296
TI  - Open versus laparoscopic cholecystectomy in acute cholecystitis. Systematic
      review and meta-analysis.
AB  - INTRODUCTION: Laparoscopic cholecystectomy (LC) has become a popular alternative
      to open cholecystectomy (OC) in the treatment of acute cholecystitis (AC).
      Laparoscopic cholecystectomy (LC) is now considered the gold standard of therapy
      for symptomatic cholelithiasis and chronic cholecystitis. However no definitive
      data on its use in AC has been published. CIAO and CIAOW studies demonstrated
      48.7% of AC were still operated with the open technique. The aim of the present
      meta-analysis is to compare OC and LC in AC. MATERIAL AND METHODS: A systematic
      review with meta-analysis and meta-regression of trials comparing open vs.
      laparoscopic cholecystectomy in patients with AC was performed. Electronic
      searches were performed using Medline, Embase, PubMed, Cochrane Central Register
      of Controlled Trials (CCTR), Cochrane Database of Systematic Reviews (CDSR) and
      CINAHL. RESULTS: Ten trials have been included with a total of 1248 patients: 677
      in the LC and 697 into the OC groups. The post-operative morbidity rate was half
      with LC (OR = 0.46). The post-operative wound infection and pneumonia rates were
      reduced by LC (OR 0.54 and 0.51 respectively). The post-operative mortality rate
      was reduced by LC (OR = 0.2). The mean postoperative hospital stay was
      significantly shortened in the LC group (MD = -4.74 days). There were no
      significant differences in the bile leakage rate, intraoperative blood loss and
      operative times. CONCLUSIONS: In acute cholecystitis, post-operative morbidity,
      mortality and hospital stay were reduced by laparoscopic cholecystectomy.
      Moreover pneumonia and wound infection rate were reduced by LC. Severe hemorrhage
      and bile leakage rates were not influenced by the technique. Cholecystectomy in
      acute cholecystitis should be attempted laparoscopically first.

PMID- 25958298
TI  - Maternal omega-3 fatty acids and micronutrients modulate fetal lipid metabolism:
      A review.
AB  - It is well established that alterations in the mother's diet or metabolism during
      pregnancy has long-term adverse effects on the lipid metabolism in the offspring.
      There is growing interest in the role of specific nutrients especially omega-3
      fatty acids in the pathophysiology of lipid disorders. A series of studies
      carried out in humans and rodents in our department have consistently suggested a
      link between omega-3 fatty acids especially docosahexaenoic acid and
      micronutrients (vitamin B12 and folic acid) in the one carbon metabolic cycle and
      its effect on the fatty acid metabolism, hepatic transcription factors and DNA
      methylation patterns. However the association of maternal intake or metabolism of
      these nutrients with fetal lipid metabolism is relatively less explored. In this
      review, we provide insights into the role of maternal omega-3 fatty acids and
      vitamin B12 and their influence on fetal lipid metabolism through various
      mechanisms which influence phosphatidylethanolamine-N-methyltransferase activity,
      peroxisome proliferator activated receptor, adiponectin signaling pathway and
      epigenetic process like chromatin methylation. This will help understand the
      possible mechanisms involved in fetal lipid metabolism and may provide important
      clues for the prevention of lipid disorders in the offspring.

PMID- 25958299
TI  - Metabolomics in cardiovascular diseases.
AB  - Cardiovascular diseases (CVDs) are the main cause of death globally. There is a
      need for the development of specific diagnostic methods, more effective
      therapeutic procedures as well as drugs, which can decrease the risk of deaths in
      the course of CVDs. For this reason, better understanding and explanation of
      molecular pathomechanisms of CVDs are essential. Metabolomics is focused on
      analysis of metabolites, small molecules which reflect the state of an organism
      in a certain point of time. Application of metabolomics approach in the
      investigation of molecular processes responsible for CVDs development may provide
      valuable information. In this article we overviewed recent reports employing
      application of untargeted and targeted metabolomic analyses in particular CVDs.
      Moreover, we focused on applications of various analytical platforms and
      metabolomics approaches which may contribute to the explanation of the
      pathomechanisms of different cardiovascular diseases. 

PMID- 25958300
TI  - Biologics for the prevention of postoperative Crohn's disease recurrence: A
      systematic review and meta-analysis.
AB  - AIM: To evaluate the efficacy and safety of biologics in the prevention of
      postoperative recurrence of Crohn's disease. METHODS: Published papers and
      conference literatures were screened for suitable studies. The main outcome
      measures were clinical, endoscopic recurrence and adverse events. RESULTS: Seven
      controlled trials met the inclusion criteria for this meta-analysis. At one year
      postoperation, the biologic therapies showed significant preventative effects in
      clinical recurrence (RR=0.36, 95% CI: 0.16-0.79; P=0.01), endoscopic recurrence
      (RR=0.16, 95% CI: 0.07-0.34; P<0.01) and severe endoscopic recurrence (RR=0.17,
      95% CI: 0.04-0.71; P=0.02) when compared with the control arms. Similarly, two
      years postresection, the use of biologics significantly reduced the risk of
      clinical, endoscopic and severe endoscopic recurrence relative to the controls.
      Although the biologic agents were not more effective than azathioprine in
      preventing clinical recurrence (P=0.14), they were more effective in preventing
      endoscopic recurrence (RR=0.09, 95% CI: 0.02-0.47; P<0.01). Moreover,
      administration of the biologics was not associated with any significant
      difference in the rate of adverse events (RR=1, 95% CI: 0.75-1.34; P=0.99) or
      severe adverse events (RR=1.03, 95% CI: 0.33-3.26; P=0.96) when compared with
      controls. CONCLUSION: Biologics are superior to azathioprine and traditional
      therapies and are not associated with increased adverse events in the
      postoperative treatment of Crohn's disease.

PMID- 25958301
TI  - Negative and positive temperature dependence of potassium leak in MscS mutants:
      Implications for understanding thermosensitive channels.
AB  - Bacterial mechanosensitive channel of small conductance (MscS) is a protein,
      whose activity is modulated by membrane tension, voltage and cytoplasmic
      crowding. MscS is a homoheptamer and each monomer consists of three transmembrane
      helices (TM1-3). Hydrophobic pore of the channel is made of TM3s surrounded by
      peripheral TM1/2s. MscS gating is a complex process, which involves opening and
      inactivation in response to the increase of membrane tension. A number of MscS
      mutants were isolated. Among them mutants affecting gating have been found
      including gain-of-function (GOF) and loss-of-function (LOF) that open at lower or
      at higher thresholds, respectively. Previously, using an in vivo screen we
      isolated multiple MscS mutants that leak potassium and some of them were GOF or
      LOF. Here we show that for a subset of these mutants K+ leak is negatively (NTD)
      or positively (PTD) temperature dependent. We show that temperature reliance of
      these mutants does not depend on how MS gating is affected by a particular
      mutation. Instead, we argue that NTD or PTD leak is due to the opposite
      allosteric coupling of the structures that determine the temperature dependence
      to the channel gate. In PTD mutants an increased hydration of the pore vestibule
      is directly coupled to the increase in the channel conductance. In NTD mutants,
      at higher temperatures an increased hydration of peripheral structures leads to
      complete separation of TM3 and a pore collapse.

PMID- 25958302
TI  - Perinatal Inhibition of NF-KappaB Has Long-Term Antihypertensive and
      Renoprotective Effects in Fawn-Hooded Hypertensive Rats.
AB  - BACKGROUND: Inhibition of transcription factor nuclear factor-kappa B (NFkappaB)
      is beneficial in various models of hypertension and renal disease. We
      hypothesized first that NFkappaB inhibition during renal development ameliorates
      hereditary hypertensive renal disease and next whether this was mediated via
      suppression of peroxisome proliferator-activated receptor (PPAR)gamma coactivator
      1alpha (PGC-1alpha). METHODS AND RESULTS: Prior to the development of renal
      injury in fawn-hooded hypertensive (FHH) rats, a model of hypertension,
      glomerular hyperfiltration, and progressive renal injury, NFkB activity, measured
      by nuclear protein expression of NFkB subunit p65, was enhanced twofold in 2-day
      old male and female FHH kidneys as compared to normotensive Wistar-Kyoto (WKY)
      rats (P < 0.05). Treating FHH dams with pyrrolidine di thio carbamate (PDTC), an
      NFkappaB inhibitor, from 2 weeks before birth to 4 weeks after birth diminished
      NFkB activity in 2-day-FHH offspring to 2-day-WKY levels (P < 0.01). Perinatal
      PDTC reduced systolic blood pressure from 20 weeks onwards by on average 25 mm Hg
      (P < 0.001) and ameliorated proteinuria (P < 0.05) and glomerulosclerosis (P <
      0.05). In kidneys of 2-day-, 2-week-, and adult offspring of PDTC-treated FHH
      dams, PGC-1alpha was induced on average by 67% (quantitative polymerase chain
      reaction (qPCR)) suggesting that suppression of this factor by NFkB could be
      involved in renal damage. Follow-up experiments with perinatal pioglitazone
      (Pio), a PPARgamma agonist, failed to confer persistent antihypertensive or
      renoprotective effects. CONCLUSIONS: Perinatal inhibition of enhanced active
      renal NFkappaB in 2-day FHH had persistent antihypertensive and renoprotective
      effects. However, this was not the case for PPARgamma stimulation. NFkB
      stimulation is therefore involved in renal damage in the FHH model of proteinuric
      renal disease by pathways other than via PPARgamma.

PMID- 25958303
TI  - A Novel Swine Model of Spontaneous Hypertension With Sympathetic Hyperactivity
      Responds Well to Renal Denervation.
AB  - BACKGROUND: The large animal model of arterial hypertension is very valuable to
      test the antihypertensive drugs and devices. We characterized a novel swine model
      of spontaneous hypertension and investigated its response to renal denervation
      (RDN). METHODS: The blood pressure (BP), levels of plasma catecholamines and
      urine vanillylmandelic acid, and the protein expressions of angiotensin
      converting enzyme (ACE) and angiotensin II type 1 (AT1), and type 2 (AT2)
      receptors in the rostral ventrolateral medulla (RVLM) were compared between
      domestic pigs and Guizhou mini-pigs. Twelve-month-old Guizhou mini-pigs were
      divided into sham (n = 7) and ablation (n = 7) groups. The mini-pigs in ablation
      group received bilateral percutaneous RDN with a saline-irrigated Sniper ablation
      catheter. Three months after the procedure, the BP was measured and the histology
      of renal nerves and arteries was analyzed. RESULTS: The mini-pigs spontaneously
      developed hypertension by the age of 6 months and the BP (162.2 +/- 11.4/111.8 +/
      9.2mm Hg) was significantly higher than age-matched domestic pigs (137.5 +/-
      1.9/80.2 +/- 4.1mm Hg, P < 0.05). The levels of plasma catecholamines and urine
      vanillylmandelic acid were higher in mini-pigs than domestic pigs. The
      expressions of ACE and AT1 were increased, but the AT2 was decreased, in RVLM
      from mini-pigs compared with domestic pigs. Three months after the procedure, the
      BP was sharply reduced in ablation group (113.8 +/- 14.4/79.4 +/- 11.7 mm Hg)
      compared with sham group (192.4 +/- 10.5/141.2 +/- 5.9 mm Hg, P < 0.01). Renal
      nerves were substantially destroyed, while renal arteries and function were not
      significantly affected by ablation. CONCLUSIONS: The Guizhou mini-pig is a novel
      spontaneous hypertensive animal model with sympathetic hyperactivity and responds
      well to RDN.

PMID- 25958304
TI  - Sigmoid stricture associated with diverticular disease should be an indication
      for elective surgery with lymph node clearance.
AB  - BACKGROUND: The literature concerning stricture secondary to diverticulitis is
      poor. Stricture in this setting should be an indication for surgery because (a)
      of the potential risk of cancer and (b) morbidity is not increased compared to
      other indications for colectomy. The goal of this report is to study the post
      surgical morbidity and the quality of life in patients after sigmoidectomy for
      sigmoid stricture associated with diverticular disease. METHOD: This is a
      monocenter retrospective observational study including patients with a
      preoperative diagnosis of sigmoid stricture associated with diverticular disease
      undergoing operation between Jan 1, 2007 and Dec 31, 2013. The GastroIntestinal
      Quality of Life Index was used to assess patient satisfaction. RESULTS: Sixteen
      patients were included of which nine were female. Median age was 69.5 (46-84) and
      the median body mass index was 23.55kg/m(2) (17.2-28.4). Elective sigmoidectomy
      was performed in all 16 patients. Overall, complications occurred in five
      patients (31.2%) (4 minor complications and 1 major complication according to the
      Dindo and Clavien Classification); none resulted in death. Pathology identified
      two adenocarcinomas (12.5%). The mean GastroIntestinal Quality of Life Index was
      122 (67-144) and 10/11 patients were satisfied with their surgical intervention.
      CONCLUSION: Sigmoid stricture prevents endoscopic exploration of the entire colon
      and thus it may prove difficult to rule out a malignancy. Surgery does not impair
      the quality of life since morbidity is similar to other indications for
      sigmoidectomy. For these reasons, we recommend that stricture associated with
      diverticular disease should be an indication for sigmoidectomy including lymph
      node clearance.

PMID- 25958305
TI  - Influence of Acyclic Nucleoside Phosphonate Antivirals on Gene Expression of
      Chemokine Receptors CCR5 and CXCR4.
AB  - Acyclic nucleoside phosphonates (ANPs) are potent antiviral agents effective
      against replication of DNA viruses and retroviruses including human
      immunodeficiency virus (HIV). Prototype compound 9-(R)-[2
      (phosphonomethoxy)propyl]adenine (tenofovir) is a principal component of drugs
      widely used in the treatment of HIV infection (Viread, Truvada). Besides their
      antimetabolic mode of action, ANPs possess immunomodulatory properties. A number
      of them have been previously found to stimulate secretion of cytokines and anti
      HIV effective chemokines. In the present pilot experiments we analysed the in
      vitro effects of ANPs on the expression of chemokine receptors CCR5 and CXCR4
      that are co-receptors of HIV-1 entry in cells. The impact of ANPs was
      investigated at the level of gene transcription of mRNA in mouse lymphocytes and
      macrophages using the RT-PCR method. The following compounds were included in the
      study: 9-(R)-[2-(phosphonomethoxy) propyl]adenine (tenofovir), N6-cyclopropyl-(R)
      9-[2-(phosphonomethoxy)-propyl]2,6-diaminopurine, N6-cyclopentyl-(R)-9-[2
      (phosphonomethoxy) propyl]2,6-diaminopurine, N6-dimethylaminoethyl-(R)-9-[2
      (phosphonomethoxy)propyl]2,6-diaminopurine, N6-cyclopentyl-9-[2
      (phosphonomethoxy) ethyl]2,6-diaminopurine, N6-isobutyl-9-[2-(phosphonomethoxy)
      ethyl]2,6-diaminopurine. Gene transcription of chemokine receptors CCR5 and CXCR4
      was not affected after application of these acyclic nucleoside phosphonate
      antivirals. 

PMID- 25958306
TI  - VLA4 Gene Polymorphism and Susceptibility to Multiple Sclerosis in Slovaks.
AB  - Multiple sclerosis (MS) is an inflammatory autoimmune disease occurring in
      genetically sensitive individuals. As migration of immune cells into the CNS is
      facilitated by the Very Late Antigen 4 (VLA-4) integrin molecule, the VLA4 gene
      may be considered as a plausible candidate genetic risk factor for susceptibility
      to MS. Therefore, the objective of our study was to investigate the association
      between two genetic polymorphisms located in the VLA4 gene and the risk of
      multiple sclerosis. One hundred seventeen MS patients and 165 control subjects
      from Slovakia were genotyped for VLA4 gene SNP polymorphisms at positions 269
      (C/A) and 3061 (A/G). The same study cohorts were also genotyped for the
      rs3135388 polymorphism tagging the HLA-DRB1*15:01 allele, which is a known
      genetic factor associated with susceptibility to develop MS in many populations.
      Our findings show for the first time that the rs3135388 polymorphism is a strong
      risk factor for MS in the Slovak population. Investigation of the VLA4 gene
      polymorphisms revealed a significantly higher frequency of the 3061AG genotype in
      MS patients compared to the controls (P <= 0.05). We suggest that the 3061AG
      polymorphic variant is an independent genetic risk factor for MS development in
      our population as it was significantly associated with this disease. The
      association was also confirmed after applying multivariate logistic-regression
      analysis adjusted for gender, age and HLA-DRB1*15:01 positivity as possible
      influencing factors. 

PMID- 25958307
TI  - Histomorphometrical and electron microscopic study of adrenocorticocytes
      following surgically induced extrahepatic biliary obstruction in adult female
      albino rats.
AB  - Cholestasis, which is a component of many liver diseases, is often associated
      with symptoms that resemble clinical adrenal insufficiency. This work aimed to
      study the histomorphometrical and electron microscopic structure of
      adrenocorticocytes after surgical induction of bile duct resection (BDR) in adult
      female albino rats. Sixty rats were randomly divided into control, BDR and sham
      operated groups. Six weeks after surgery, the blood serum of the rats was
      examined biochemically, and the suprarenal cortexes were prepared for
      histological, morphometrical and statistical studies. The BDR group showed a
      highly significant increase in bilirubin and serum alkaline phosphatase levels,
      whereas aldosterone and cortisol levels were highly significantly decreased. The
      area percentages of positive immunoreactions for P53, cyclooxygenase II (COX-II)
      and inducible nitric oxide synthase (INOS) revealed highly significant increases
      in the BDR group. Electron microscopic examination of the BDR group showed marked
      cytoplasmic vacuolations, large lipid droplets, swollen mitochondria and many
      small dark nuclei in the adrenocorticocytes. The zona fasciculata had
      heterogeneously electron-dense mitochondria and dilated smooth endoplasmic
      reticulum. Some of the zona reticularis cells contained lipofuscin pigments. The
      surgical induction of BDR produced deleterious effects on the structure and
      function of the adrenocorticocytes. A long-term study using different animal
      species is recommended for further examination. 

PMID- 25958308
TI  - Antioxidant status in blood of gynaecological patients: influence of diagnosis
      and reproductive factors.
AB  - Cancer of the reproductive tract is an important cause of morbidity and mortality
      among women worldwide. In this study we evaluated the influence of diagnostic
      categories, age and reproductive factors on antioxidant enzymes and lipid
      hydroperoxides in the blood of gynaecological patients diagnosed with endometrial
      polyp, myoma, hyperplasia simplex, hyperplasia complex and endometrial
      adenocarcinoma. Multivariate regression analysis was used to assess the
      association of diagnosis, age, parity, abortions and abnormal uterine bleeding
      with the examined parameters. Diagnosis provided the best predictive model for
      superoxide dismutase, catalase and glutathione peroxidase activities, and also
      for the lipid hydroperoxide level. Abortions fitted the best predictive model for
      superoxide dismutase activity. A significant correlation was also found between
      the predictor variables themselves. This study showed that reproductive and other
      factors may be associated, at least partially, with antioxidant capacity and
      ability to defend against the oxidative damage in gynaecological patients with
      various diagnoses. 

PMID- 25958309
TI  - Manufactured silver nanoparticles of different sizes induced DNA strand breaks
      and oxidative DNA damage in hepatoma and leukaemia cells and in dermal and
      pulmonary fibroblasts.
AB  - Many classes of silver nanoparticles (AgNPs) have been synthesized and widely
      applied, but no conclusive information on their potential cytotoxicity and
      genotoxicity mechanisms is available. Therefore, the purpose of this study was to
      compare the potential genotoxic effects (DNA strand breaks and oxidative DNA
      damage) of 4.7 nm coated and 42 nm uncoated AgNPs, using the comet assay, in four
      relevant human cell lines (hepatoma, leukaemia, and dermal and pulmonary
      fibroblasts) in order to understand the impact of such nanomaterials on cellular
      DNA. The results indicated that in all cell lines tested, 4.7 nm coated (0.1-1.6
      MUg ml-1) and 42 nm uncoated (0.1-6.7 MUg ml-1) AgNPs increased DNA strand breaks
      in a dose- and size-dependent manner following 24 h treatment, the smaller AgNPs
      being more genotoxic. Human pulmonary fibroblasts showed the highest sensitivity
      to the AgNPs. A modified comet assay using endonuclease III and
      formamidopyrimidine- DNA glycosylase restriction enzymes showed that in tumoral
      and normal human dermal fibroblasts, pyrimidines and purines were oxidatively
      damaged by both AgNPs, but the damage was not size-dependent. However, in human
      pulmonary fibroblasts, no oxidative damage was observed after treatment with 42
      nm AgNPs. In conclusion, both AgNP sizes induced DNA damage in human cells, and
      this damage could be related to oxidative stress.

PMID- 25958310
TI  - Association of MicroRNA-146a rs2910164 Gene Polymorphism with Metabolic Syndrome.
AB  - Alteration in microRNA-146a (miRNA-146a) expression is an important event in the
      pathogenesis of many human diseases. MiRNA-146a rs2910164 is a functional
      polymorphism that showed association with several diseases. Metabolic syndrome is
      an aggregation of multiple risk factors including impaired glucose tolerance,
      increased highdensity lipoprotein, abdominal obesity, and high blood pressure.
      The aim of this study was to assess the relation of miRNA-146a rs2910164 with
      metabolic syndrome and its component traits in Egyptian women from the Suez Canal
      area. The study included 100 healthy female subjects and 100 metabolic syndrome
      patients. The component traits of metabolic syndrome were determined and the
      genotypes of the polymorphisms were assessed using the polymerase chain reaction
      restriction fragment length polymorphism technique using the restriction enzyme
      Hpy188I. The rare C allele had a significantly higher frequency in metabolic
      syndrome patients (P = 0.013). The heterozygote GC and the rare CC genotypes
      showed a significant increase in body mass index, waist circumference,
      triglycerides, total cholesterol, low-density lipoprotein, systolic and diastolic
      blood pressure. The GC genotype was associated with higher fasting blood glucose,
      fasting serum insulin and insulin resistance. The carriers of CC genotype had
      significantly lower HDL compared with the GG genotype carriers. In conclusion,
      The C allele of miRNA-146a rs2910164 showed positive association with increased
      susceptibility to metabolic syndrome and its phenotypes in the study population. 

PMID- 25958311
TI  - Erratum: Longer hospital stay is associated with high rates of tuberculosis
      related morbidity and mortality within 12 months after discharge in a referral
      hospital in Sub-Saharan Africa.

PMID- 25958312
TI  - Homologues of potato chromosome 5 show variable collinearity in the euchromatin,
      but dramatic absence of sequence similarity in the pericentromeric
      heterochromatin.
AB  - BACKGROUND: In flowering plants it has been shown that de novo genome assemblies
      of different species and genera show a significant drop in the proportion of
      alignable sequence. Within a plant species, however, it is assumed that different
      haplotypes of the same chromosome align well. In this paper we have compared
      three de novo assemblies of potato chromosome 5 and report on the sequence
      variation and the proportion of sequence that can be aligned. RESULTS: For the
      diploid potato clone RH89-039-16 (RH) we produced two linkage phase controlled
      and haplotype-specific assemblies of chromosome 5 based on BAC-by-BAC sequencing,
      which were aligned to each other and compared to the 52 Mb chromosome 5 reference
      sequence of the doubled monoploid clone DM 1-3 516 R44 (DM). We identified 17.0
      Mb of non-redundant sequence scaffolds derived from euchromatic regions of RH and
      38.4 Mb from the pericentromeric heterochromatin. For 32.7 Mb of the RH sequences
      the correct position and order on chromosome 5 was determined, using genetic
      markers, fluorescence in situ hybridisation and alignment to the DM reference
      genome. This ordered fraction of the RH sequences is situated in the euchromatic
      arms and in the heterochromatin borders. In the euchromatic regions, the sequence
      collinearity between the three chromosomal homologs is good, but interruption of
      collinearity occurs at nine gene clusters. Towards and into the heterochromatin
      borders, absence of collinearity due to structural variation was more extensive
      and was caused by hemizygous and poorly aligning regions of up to 450 kb in
      length. In the most central heterochromatin, a total of 22.7 Mb sequence from
      both RH haplotypes remained unordered. These RH sequences have very few syntenic
      regions and represent a non-alignable region between the RH and DM
      heterochromatin haplotypes of chromosome 5. CONCLUSIONS: Our results show that
      among homologous potato chromosomes large regions are present with dramatic loss
      of sequence collinearity. This stresses the need for more de novo reference
      assemblies in order to capture genome diversity in this crop. The discovery of
      three highly diverged pericentric heterochromatin haplotypes within one species
      is a novelty in plant genome analysis. The possible origin and cytogenetic
      implication of this heterochromatin haplotype diversity are discussed.

PMID- 25958313
TI  - The role of c-Src in the invasion and metastasis of hepatocellular carcinoma
      cells induced by association of cell surface GRP78 with activated alpha2M.
AB  - BACKGROUND: Emerging data have suggested that cell surface GRP78 is a
      multifunctional receptor and has been linked to proliferative and antiapoptotic
      signaling cascades. Activated alpha2-macroglobin (alpha2M*) is a natural
      circulating ligand of cell surface GRP78. Association of cell surface GRP78 with
      alpha2M* is involved in the regulation of cell proliferation, survival and
      apoptosis in human cancers. METHODS: The invasion and metastasis of HCC cells
      were examined using transwell and wound healing assay; Cell surface expression of
      GRP78 was detected by in cell western assay. Translocation of GRP78 from cytosol
      to cell surface was observed by transfection of GRP78-EGFP plus TRIRC-WGA
      staining. The levels of Src, phosphor-Src, FAK, phospho-FAK, EGFR, phospho-EGFR,
      phospho-Cortactin, phospho-Paxillin were determined by western blot. Cell surface
      expression of GRP78 in HCC tissue samples was observed by immunofluorescence. The
      distribution of Paxillin and Cortactin in HCC cells was also observed by
      immunofluorescence. The interaction between GRP78 and Src were detected by far
      western blot, co-immunoprecipitation and GST pulldown. GRP78 mRNA was detected by
      RT-PCR. RESULTS: In the current study, we showed that association of cell surface
      GRP78 with alpha2M* stimulated the invasion and metastasis of HCC. Cell surface
      GRP78 could interact directly with c-Src, promoted the phosphorylation of c-Src
      at Y416. Inhibition of the tyrosine kinase activity of c-Src with PP2 reverted
      the stimulatory effect caused by association of cell surface GRP78 with alpha2M*.
      Moreover, association of cell surface GRP78 with alpha2M* facilitates the
      interaction between EGFR and c-Src and consequently phosphorylated EGFR at Y1101
      and Y845, promoting the invasion and metastasis of HCCs. However, inhibition of
      the tyrosine kinase of c-Src do not affect the interaction between EGFR and Src.
      CONCLUSION: c-Src plays a critical role in the invasion and metastasis of HCC
      induced by association of cell surface GRP78 with alpha2M*. Cell surface GRP78
      directly binds and phosphorylates c-Src. As a consequence, c-Src phosphorylated
      EGFR, promoting the invasion and metastasis of HCCs.

PMID- 25958315
TI  - Psychometric Properties of the Centrality of Pain Scale.
AB  - The Centrality of Pain Scale (COPS) is a recently developed patient-centered, 10
      item self-report measure designed to assess how central, or dominating, in their
      lives individuals with chronic pain perceive pain to be. The COPS underwent
      initial development and validation previously; preliminary results suggested that
      the measure had excellent psychometric properties and that COPS scores were
      associated with important clinical factors. The purpose of the present study was
      to examine the psychometric properties of the COPS in a sample of individuals
      with mixed chronic pain diagnoses (N = 178) being treated at a U.S. Veterans
      Affairs Medical Center. Principal components analysis of COPS items revealed a
      single factor, and all items loaded highly. The COPS had high internal
      consistency (Cronbach's alpha = .902) and was significantly correlated with other
      measures of pain, mental health, psychological factors associated with pain, and
      chronic pain coping styles, suggesting convergent and divergent validity.
      Hierarchical linear regression analyses indicated that COPS score was
      independently associated with both pain severity and interference. Future
      research should evaluate the generalizability of the COPS in different samples,
      its responsiveness to treatment, and the extent to which pain centrality may be a
      focus of nonpharmacologic interventions for chronic pain. PERSPECTIVE: We
      conducted psychometric testing of the COPS, a recently developed patient-centered
      self-report measure designed to examine how central or dominating pain is to a
      person's life. Study results indicated a reliable and valid measure, which was
      significantly associated with pain severity and interference, even after
      controlling for demographic and clinical factors.

PMID- 25958314
TI  - Diet-induced changes in n-3- and n-6-derived endocannabinoids and reductions in
      headache pain and psychological distress.
AB  - Omega-3 and omega-6 fatty acids are biosynthetic precursors of endocannabinoids
      with antinociceptive, anxiolytic, and neurogenic properties. We recently reported
      that targeted dietary manipulation-increasing omega-3 fatty acids while reducing
      omega-6 linoleic acid (the H3-L6 intervention)-reduced headache pain and
      psychological distress among chronic headache patients. It is not yet known
      whether these clinical improvements were due to changes in endocannabinoids and
      related mediators derived from omega-3 and omega-6 fatty acids. We therefore used
      data from this trial (N = 55) to investigate 1) whether the H3-L6 intervention
      altered omega-3- and omega-6-derived endocannabinoids in plasma and 2) whether
      diet-induced changes in these bioactive lipids were associated with clinical
      improvements. The H3-L6 intervention significantly increased the omega-3
      docosahexaenoic acid derivatives 2-docosahexaenoylglycerol (+65%, P < .001) and
      docosahexaenoylethanolamine (+99%, P < .001) and reduced the omega-6 arachidonic
      acid derivative 2-arachidonoylglycerol (-25%, P = .001). Diet-induced changes in
      these endocannabinoid derivatives of omega-3 docosahexaenoic acid, but not omega
      6 arachidonic acid, correlated with reductions in physical pain and psychological
      distress. These findings demonstrate that targeted dietary manipulation can alter
      endocannabinoids derived from omega-3 and omega-6 fatty acids in humans and
      suggest that 2-docosahexaenoylglycerol and docosahexaenoylethanolamine could have
      physical and/or psychological pain modulating properties. TRIAL REGISTRATION:
      ClinicalTrials.gov (NCT01157208) PERSPECTIVE: This article demonstrates that
      targeted dietary manipulation can alter endocannabinoids derived from omega-3 and
      omega-6 fatty acids and that these changes are related to reductions in headache
      pain and psychological distress. These findings suggest that dietary
      interventions could provide an effective, complementary approach for managing
      chronic pain and related conditions.

PMID- 25958317
TI  - SWATH analysis of the synaptic proteome in Alzheimer's disease.
AB  - Brain tissue from Alzheimer's disease patients exhibits synaptic degeneration in
      selected regions. Synaptic dysfunction occurs early in the disease and is a
      primary pathological target for treatment. The molecular mechanisms underlying
      this degeneration remain unknown. Quantifying the synaptic proteome in autopsy
      brain and comparing tissue from Alzheimer's disease cases and subjects with
      normal aging are critical to understanding the molecular mechanisms associated
      with Alzheimer pathology. We isolated synaptosomes from hippocampus and motor
      cortex so as to reduce sample complexity relative to whole-tissue homogenates.
      Synaptosomal extracts were subjected to strong cation exchange (SCX)
      fractionation to further partition sample complexity; each fraction received
      SWATH-based information-dependent acquisition to generate a comprehensive peptide
      ion library. The expression of synaptic proteins from AD hippocampus and motor
      cortex was then compared between groups. A total of 2077 unique proteins were
      identified at a critical local false discovery rate <5%. Thirty of these,
      including 17 novel proteins, exhibited significant expression differences between
      cases and controls; these proteins are involved in cellular functions including
      structural maintenance, signal transduction, autophagy, oxidative stress, and
      proteasome activity, or they have synaptic-vesicle related or energy-related
      functions. Differentially expressed proteins were subjected to pathway analysis
      to identify protein-protein interactions. This revealed that the most perturbed
      molecular and cellular functions were cellular assembly and organization. Core
      analysis revealed RhoA signaling to be the top canonical pathway. Network
      analysis showed that differentially expressed proteins were related to cellular
      assembly and organization, and cellular function and maintenance. This is the
      first study to combine SCX fractionation with SWATH analysis. SWATH is a
      promising new technique that can greatly enhance protein identification in any
      proteome, and has many other benefits; however, there are limitations yet to be
      resolved. 

PMID- 25958316
TI  - Body composition is associated with multisite lower body musculoskeletal pain in
      a community-based study.
AB  - Population-based studies suggest that pain in the lower body is common and that
      pain at multiple sites is more prevalent than single-site pain. Obesity is a risk
      factor for multisite musculoskeletal pain, but there are limited data on the role
      of body composition. Therefore, we sought to determine whether body composition
      is associated with multisite musculoskeletal pain involving the low back, knee,
      and foot. A total of 133 participants were recruited for a study examining the
      relationship between obesity and musculoskeletal disease. Participants completed
      validated questionnaires that examined levels of pain at the low back, knee, and
      foot. Body composition was assessed using dual-energy x-ray absorptiometry.
      Multisite pain was common, with 26.3% of participants reporting pain at 2 sites
      and 31.6% at 3 sites, and only 20% were pain free. The low back was the most
      common site of pain (63%). Greater fat mass and fat mass index, but not fat-free
      mass, were associated with pain at a greater number of sites, independent of age,
      gender, and fat-free mass (P < .01). Longitudinal studies exploring the mechanism
      of action by which increased fat mass is associated with pain may provide
      important insights into therapeutic strategies for the prevention of multisite
      pain. PERSPECTIVE: Greater fat mass and fat mass index were associated with a
      greater number of lower body pain sites, with no association observed for fat
      free mass. Understanding the mechanism by which increased fat mass is associated
      with pain may provide important insights into therapeutic strategies for the
      prevention of pain.

PMID- 25958318
TI  - The effect of weight-based chemotherapy dosing in a cohort of gynecologic
      oncology patients.
AB  - OBJECTIVE: Many clinicians limit chemotherapy doses based on a maximum body
      surface area (BSA) of 2m(2). We sought to determine how chemotherapy-related
      toxicities compared between groups of patients that varied with respect to BSA.
      We hypothesized that obese patients receiving weight-based (WB) dosing would not
      have significantly higher chemotherapy-related toxicities than control groups.
      METHODS: We performed a retrospective review of patients with BSA>=2m(2) who
      received WB chemotherapy for a gynecologic cancer between January and August
      2013. Subjects were matched with two controls: patients with BSA<2m(2) who
      received WB dosing, and patients with BSA>=2m(2) who received capped dosing at
      BSA=2m(2). Groups were matched for medical co-morbidities and prior cancer
      treatment. Demographic and clinical information was extracted and analyzed via
      ANOVA and Fisher's exact test. RESULTS: A total of 75 patients were included. The
      three groups were similar in their medical co-morbidities and prior cancer
      treatment. When comparing pre- and post-treatment laboratory values, there was no
      difference in hematologic toxicities. There was no difference between groups with
      regard to treatment delays, unplanned admissions, transfusions, or dose
      reductions for toxicity. CONCLUSIONS: Gynecologic cancer patients with BSA>=2m(2)
      treated with WB chemotherapy had no increase in hematologic or non-hematologic
      toxicities when compared to controls. Consideration should be given to using WB
      dosing in obese patients with gynecologic malignancies. Further investigation is
      required to determine the effect of WB dosing on progression-free and overall
      survival in obese gynecologic cancer patients.

PMID- 25958319
TI  - A phase I study of IV doxorubicin plus intraperitoneal (IP) paclitaxel and IV or
      IP cisplatin in endometrial cancer patients at high risk for peritoneal failure
      (GOG 9920): an NRG Oncology/Gynecologic Oncology Group study.
AB  - OBJECTIVE: To determine the maximum tolerated dose (MTD) of a modified
      paclitaxel/doxorubicin/cisplatin (TAP) regimen which incorporated intraperitoneal
      (IP) paclitaxel or IP paclitaxel/cisplatin in advanced endometrial cancer.
      METHODS: Patients (pts) with FIGO (1998) Stage IIIA/IIIC with positive cytologic
      washings/ascites, adnexa, or serosa or Stage IV (intraperitoneal disease spread),
      histologically confirmed endometrial cancer were eligible. The study was designed
      as a phase I, 3+3 dose escalation study evaluating 5 dose levels (DL). All pts
      received cycles 1-2 with IV TAP, and cycles 3-6 with IV/IP therapy, on a 21day
      schedule. Adverse events were evaluated on cycles 3-4 for dose limiting toxicity
      (DLT) and dose escalation decisions. RESULTS: Twenty-one pts were enrolled, of
      which 17 were evaluable for DLT. Most pts had Stage IV disease (76%) and
      serous/clear cell histology (59%). The MTD was determined to be DL 3 (cycles 3-6
      including paclitaxel 90mg/m(2) IP, doxorubicin 45mg/m(2) IV, cisplatin
      50mg/m(2)). Three DLT events occurred and were related to grades 3-4 metabolic
      toxicities. There was one grade 2 sensory neuropathy event and myelosupression
      was tolerable without the use of G-CSF. 88% of evaluable pts completed 6cycles of
      therapy. With a median follow-up of 22months, 46% of patients remain progression
      free at 2years. CONCLUSION: We described an IV/IP based modification of a
      standard TAP regimen in endometrial cancer. Based on the high rate of completing
      6cycles of therapy, low rates of neuropathy, and promising PFS, further study of
      IP therapy in endometrial cancer is warranted.

PMID- 25958320
TI  - TP53 hot spot mutations in ovarian cancer: selective resistance to microtubule
      stabilizers in vitro and differential survival outcomes from The Cancer Genome
      Atlas.
AB  - OBJECTIVE: To test if TP53 hot spot mutations (HSMs) confer differential
      chemotherapy resistance or survival outcomes, the effects of microtubule
      stabilizers on human ovarian carcinoma cells (OCCs) expressing TP53 HSMs were
      studied in vitro. Survival outcomes of patients with high grade serous epithelial
      ovarian carcinoma (HGS EOC) expressing matched HSMs were compared using The
      Cancer Genome Atlas (TCGA) data. METHODS: Growth inhibition of OCCs transfected
      with a HSM (m175, m248 or m273) was measured during treatment with paclitaxel,
      epothilone B (epoB), or ixabepilone. Effects of epoB on p53 expression,
      phosphorylation, and acetylation, as well as p53-regulated expression of p21 and
      mdm2 proteins, were determined by Western blot analysis. Expression of p53 target
      genes P21, GADD45, BAX, PIDD, NF-kB2, PAI-1, and MDR1 was measured by RT-PCR.
      cBioPortal.org identified patients with codon R175, R248 or R273 HSMs from TCGA
      data. Survival outcomes were characterized. RESULTS: p53-m248 confers
      chemoresistance and is not acetylated during epoB treatment. m273 demonstrated
      high MDR1 expression and resistance to paclitaxel. P21, GADD45 and PAI-1
      expression were down-regulated in mutant OCCs. Optimally cytoreduced patients
      with codon R273 (n=17), R248 (n=13), R175 (n=7) HSMs, or any other TP53 mutation
      demonstrated median 14.9, 17.6, 17.8 and 16.9months (p=0.806) progression free
      survival and 84.1, 33.6, 62.1 and 44.5months (p=0.040) overall survival,
      respectively. CONCLUSIONS: Human OCCs harboring different TP53 HSMs were
      selectively resistant to microtubule stabilizers. Patients with different HSMs
      had significantly different overall survival. Both in vitro data and clinical
      experience support further studying the outcomes of particular TP53 HSMs.

PMID- 25958321
TI  - Effective application of freezing lipid precipitation and SCX-SPE for
      determination of pyrrolizidine alkaloids in high lipid foodstuffs by LC-ESI
      MS/MS.
AB  - Pyrrolizidine alkaloids (PAs) are naturally occurring plant toxins associated
      with serious hepatic disease in humans and animals. In this study, rapid and
      sensitive analytical method was developed for the determination of 9 toxic PAs in
      popularly high lipid foodstuffs by liquid chromatography-electrospray ionization
      tandem mass spectrometry (LC-ESI-MS/MS). PAs in lipid foodstuff were effectively
      purified by freezing lipid precipitation (FLP) and strong cation exchange (SCX)
      solid-phase extraction (SPE). Especially, FLP could easily remove the large
      amounts of triacylglycerols in the lipid sample extract and effectively combine
      with SPE cleanup. During the FLP procedure, over 77% of the lipids in the
      foodstuff extracts were rapidly eliminated without any significant loss of the
      PAs with over 81% recovery. The elimination efficiency of lipids by FLP was
      tested with LC-atmospheric chemical ionization (APCI)-MS. For further
      purification, SCX-SPE cartridge could successfully purify PAs from the remaining
      interfering substances by the variation pH with 5% NH4OH in methanol. For precise
      quantification and confirmation of PAs in complicate sample matrices, appropriate
      transition ions in LC-MS/MS-multiple-ion reaction monitoring (MRM) mode were
      selected on the basis of MS/MS fragmentation pathways of PAs. The established
      analytical method was validated in terms of the linearity, limits of detection
      (LOD), and quantification (LOQ), precision, and accuracy. The method was deemed
      satisfactory by inter- and intra-day validation and exhibited both high accuracy
      and precision (relative standard deviation<11.06%). Overall limits of detection
      and quantitation of PAs were approximately 0.06-0.60ng/mL at a signal-to-noise
      ratio (S/N) of 3 and were about 0.20-1.99ng/mL at a S/N of 10 for all foodstuffs.
      The established method was successfully applied for the monitoring of toxic PAs
      in several types of high lipid foodstuffs such as soybeans, seed oil, milk, and
      margarine. 

PMID- 25958322
TI  - Critical development by design of a rugged HPLC-MS/MS method for direct
      determination of ibuprofen enantiomers in human plasma.
AB  - Development and validation of a HPLC-MS/MS method for direct determination of R-
      and S-ibuprofen (Ibu) in human plasma without a need of derivatization or other
      complexities such as postcolumn infusion of solvents or reagents was performed.
      Critical steps were investigated during method development using experimental
      design to achieve a reliable and rugged assay. The LC-MS/MS separation of R-Ibu
      and S-Ibu was obtained on Lux Cellulose chiral column utilizing 0.1% (v/v) acetic
      acid in mixture of methanol and water (90:10%, v/v) as a mobile phase. Two types
      of extraction procedure for Ibu and Ketoprofen (internal standard, IS) were
      optimized using Full factorial 3(2) design (LLE) and D-Optimal Experimental
      Design (SPE). Excellent recovery values, 80% (mean) and 95% (mean) for LLE and
      SPE respectively, were obtained using 50MUL plasma. The matrix effect was
      assessed for both of the extraction procedures, including hyperlipidaemic and
      haemolyzed plasma. The extensive investigation of matrix effect showed that LLE
      yields cleaner extracts than the SPE. The result of the investigation of in vitro
      interconversion of R-Ibu and S-Ibu showed that it does not occur under the
      influence of pH, temperature, and in the overall analytical procedure. The
      validation data, adhered to EMA guideline for validation of bioanalytical
      methods, showed that the proposed method provides accurate and reproducible
      results in range of 0.1-50mg/L with a lower limit of detection of 0.02mg/L. The
      applicability of the method was demonstrated through determination of R-Ibu and S
      Ibu in human plasma after oral administration of 400mg rac-Ibu. 

PMID- 25958323
TI  - Graphite-based microextraction by packed sorbent for online extraction of beta
      blockers from human plasma samples.
AB  - In the present work a new graphitic material (Carbon-XCOS) was used as a sorbent
      for microextraction by packed sorbent (MEPS). The beta-blockers metoprolol and
      acebutolol in plasma samples were extracted and detected online using Carbon-MEPS
      syringe and liquid chromatography and tandem mass spectrometry (LC-MS/MS).
      Factors affecting the MEPS performance such as conditioning, washing and elution
      solutions were investigated. The validation of the bioanalytical method was
      performed using human plasma. The standard curve ranged from 10 to 2000nM and the
      lower limit of quantification (LLOQ) was set to 10nM. The method validation
      showed good accuracy and precision for the quality control (QC) samples at three
      concentration levels (30, 800 and 1600nM). The accuracy values of the QC samples
      were in the range of 86-108% (n=18). The precision values of intra- and inter-day
      for QC samples ranged from 4.4% to 14.4% (RSD) for the both studied analytes. The
      coefficient of determination (R(2)) values were >=0.999 (n=3). 

PMID- 25958324
TI  - The TASERed finger: A new entity. Case report and review of literature.
AB  - The TASER((r)) is a self-defense weapon whose use has now become commonplace
      among law enforcement agencies. Electronic control weapons were first used in the
      USA in the 1990s and then adopted in Europe and France. We report a case of an 18
      year-old male who presented a penetrating lesion of the middle phalanx of the
      left index finger. To the best of our knowledge, this is the first complex finger
      injury due to the TASER((r)). It highlights the potential major risks to finger
      vitality and function with use of this electrical weapon. 

PMID- 25958325
TI  - MicroRNA-128 targets myostatin at coding domain sequence to regulate myoblasts in
      skeletal muscle development.
AB  - MicroRNAs (miRNAs or miRs) play a critical role in skeletal muscle development.
      In a previous study we observed that miR-128 was highly expressed in skeletal
      muscle. However, its function in regulating skeletal muscle development is not
      clear. Our hypothesis was that miR-128 is involved in the regulation of the
      proliferation and differentiation of skeletal myoblasts. In this study, through
      bioinformatics analyses, we demonstrate that miR-128 specifically targeted mRNA
      of myostatin (MSTN), a critical inhibitor of skeletal myogenesis, at coding
      domain sequence (CDS) region, resulting in down-regulating of myostatin post
      transcription. Overexpression of miR-128 inhibited proliferation of mouse C2C12
      myoblast cells but promoted myotube formation; whereas knockdown of miR-128 had
      completely opposite effects. In addition, ectopic miR-128 regulated the
      expression of myogenic factor 5 (Myf5), myogenin (MyoG), paired box (Pax) 3 and
      7. Furthermore, an inverse relationship was found between the expression of miR
      128 and MSTN protein expression in vivo and in vitro. Taken together, these
      results reveal that there is a novel pathway in skeletal muscle development in
      which miR-128 regulates myostatin at CDS region to inhibit proliferation but
      promote differentiation of myoblast cells. 

PMID- 25958326
TI  - Development and psychometric validation of measures to assess the impact of
      phenylketonuria and its dietary treatment on patients' and parents' quality of
      life: the phenylketonuria - quality of life (PKU-QOL) questionnaires.
AB  - BACKGROUND: The aim of our study was to develop and validate the first set of PKU
      specific Health-related Quality of Life (HRQoL) questionnaires that: 1) were
      developed for patients with PKU and their parents, 2) cover the physical,
      emotional, and social impacts of PKU and its treatment on patients' lives, 3) are
      age specific (Child PKU-QOL, Adolescent PKU-QOL, Adult PKU-QOL), 4) enable the
      evaluation of the HRQoL of children by their parents (Parent PKU-QOL), and 5)
      have been cross-culturally adapted for use in seven countries (i.e. France,
      Germany, Italy, The Netherlands, Spain, Turkey and the UK). METHODS: The PKU-QOL
      questionnaires were developed according to reference methods including patients',
      parents' and healthcare professionals' interviews; testing in a pilot study
      (qualitative step in six countries), and linguistic validation of the finalised
      pilot versions in Turkish. For finalisation and psychometric validation, the
      pilot versions were included in a multicentre, prospective, non-interventional,
      observational study conducted in 34 sites in France, Germany, Italy, The
      Netherlands, Spain, Turkey and the UK. Iterative multi-trait analyses were
      conducted. Psychometric properties were assessed (concurrent and clinical
      validity, internal consistency reliability and test-retest reliability). RESULTS:
      Data from 559 subjects (306 patients, 253 parents) were analysed. After
      finalisation, the PKU-QOL questionnaires included 40 items (Child PKU-QOL), 58
      items (Adolescent PKU-QOL), 65 items (Adult PKU-QOL) and 54 items (Parent PKU
      QOL), distributed in four modules: PKU symptoms, PKU in general, administration
      of Phe-free protein supplements and dietary protein restriction. The measurement
      properties of the Adolescent, Adult and Parent PKU-QOL questionnaires were
      overall fairly satisfactory, but weaker for the Child questionnaire. CONCLUSIONS:
      The four PKU-QOL questionnaires developed for different ages (Child PKU-QOL,
      Adolescent PKU-QOL, Adult PKU-QOL), and for parents of children with PKU (Parent
      PKU-QOL) are valid and reliable instruments for assessing the multifaceted impact
      of PKU on patients of different age groups (children, adolescents and adults) and
      their parents, and are available for use in seven countries. They are very
      promising tools to explore how patients' perceptions evolve with age, to increase
      knowledge of the impact of PKU on patients and parents in different countries,
      and to help monitor the effect of therapeutic strategies.

PMID- 25958327
TI  - A cross-sectional study of the prevalence and correlates of tobacco use in
      Chennai, Delhi, and Karachi: data from the CARRS study.
AB  - BACKGROUND: Tobacco burdens in India and Pakistan require continued efforts to
      quantify tobacco use and its impacts. We examined the prevalence and
      sociodemographic and health-related correlates of tobacco use in Delhi, Chennai
      (India), and Karachi (Pakistan). METHODS: Analysis of representative surveys of
      11,260 participants (selected through multistage cluster random sampling;
      stratified by gender and age) in 2011 measured socio-demographics, tobacco use
      history, comorbid health conditions, and salivary cotinine. We used bivariate and
      multivariate regression analyses to examine factors associated with tobacco use.
      RESULTS: Overall, 51.8 % were females, and 61.6 % were below the age of 45 years.
      Lifetime (ever) tobacco use prevalence (standardized for world population) was
      45.0 %, 41.3 %, and 42.5 % among males, and 7.6 %, 8.5 %, and 19.7 % among
      females in Chennai, Delhi, and Karachi, respectively. Past 6 month tobacco use
      prevalence (standardized for world population) was 38.6 %, 36.1 %, and 39.1 %
      among males, and 7.3 %, 7.1 %, and 18.6 % among females in Chennai, Delhi, and
      Karachi, respectively. In multivariable regression analyses, residing in Delhi or
      Karachi versus Chennai; older age; lower education; earning less income; lower
      BMI; were each associated with tobacco use in both sexes. In addition, semi
      skilled occupation versus not working and alcohol use were associated with
      tobacco use in males, and having newly diagnosed dyslipidemia was associated with
      lower odds of tobacco use among females. Mean salivary cotinine levels were
      higher among tobacco users versus nonusers (235.4; CI: 187.0-283.8 vs. 29.7; CI:
      4.2, 55.2, respectively). CONCLUSION: High prevalence of tobacco use in the South
      Asian region, particularly among men, highlights the urgency to address this
      serious public health problem. Our analyses suggest targeted prevention and
      cessation interventions focused on lower socioeconomic groups may be particularly
      important.

PMID- 25958328
TI  - Treatment of periprosthetic femoral fractures after femoral revision using a long
      stem.
AB  - BACKGROUND: Periprosthetic femoral fractures are becoming increasingly common and
      are a major complication of total hip arthroplasty and hemiarthroplasty. The
      treatment of periprosthetic femoral fracture after femoral revision using a long
      stem is more complex and challenging. The purpose of this study was to identify
      the clinical and radiographical features of periprosthetic femoral fractures
      after revision using a long stem. METHODS: We report a retrospective review of
      the outcomes of treatment of 11 periprosthetic fractures after femoral revision
      using a long stem. Eleven female patients with a mean age of 79.2 years (70 to
      91) were treated for a Vancouver type B1 fracture between 1998 and 2013. The mean
      numbers of previous surgeries were 3.1 (2 to 5). RESULTS: The average follow-up
      was 58.9 months (8 to 180). We found several important features that might
      influence the outcome of treatment for periprosthetic femoral fractures after
      femoral revision using a long stem: 1) all cases were classified as Vancouver
      type B1. 2) 6 patients (55%) had a transverse fracture around the tip of the long
      stem. 3) 7 patients (64%) had a history of previous fracture of the ipsilateral
      femur. The type B1 fractures were treated with open reduction and internal
      fixation in 9 hips, 6 of which were reinforced with bone grafts. Two other
      periprosthetic fractures were treated with femoral revision. One was revised
      because of stem breakage, and the other was a transverse fracture associated with
      poor bone quality, which received a femoral revision with a long stem and a
      plate. All fractures except one achieved primary union. This failed case had a
      bone defect at the fracture site, and revision surgery using a cementless long
      stem and allografts was successful. CONCLUSIONS: These findings suggest that most
      cases of type B1 fracture after revision using a long stem have been treated
      successfully with open reduction and internal fixation. However, a transverse
      fracture with very poor bone quality might be considered as a type B3 fracture,
      and femoral revision might be a treatment of choice.

PMID- 25958329
TI  - Yeasts of the genital region of patients attending the dermatology service at
      Hospital Sao Paulo, Brazil.
AB  - BACKGROUND: The knowledge of the diversity of yeasts that make up the skin
      microbiota of human beings is essential for the efficient monitoring of
      infections to which a person may be predisposed. AIMS: This study identified
      yeasts comprising the genital skin microbiota of patients attending the
      Dermatology Service at the Hospital Sao Paulo-UNIFESP, Brazil. METHODS: Samples
      were collected from the genital region of each patient and cultured on Sabouraud
      dextrose agar. Individual colonies were carefully transferred to tubes daily.
      Yeasts were identified based on classical methodologies and confirmed using a
      commercial kit. RESULTS: Eighty-three patients were included in the study.
      Approximately 80% were women and 20% were men. The average age was 55 years.
      Hypertension, diabetes, kidney transplant and AIDS were the main underlying
      diseases reported by the patients. The most prevalent yeasts were Candida
      parapsilosis (36.1%), Rhodotorula mucilaginosa (9.2%), Rhodotorula glutinis
      (8.3%), Candida tropicalis (5.5%) and Trichosporon inkin (1.8%). Approximately
      78% of the isolates were obtained in pure cultures. Trichosporon inkin was
      isolated only from women, in contrast to literature describing a high prevalence
      in males. CONCLUSIONS: Our results suggest that Candida albicans is not the main
      yeast found on genital skin as previously thought, and opportunistic pathogens
      such as C. parapsilosis, C. tropicalis, Rhodotorula spp. and T. inkin make up the
      genital skin microbiota, representing a risk for infection in immunocompromised
      subjects. These results also indicate that women are carriers of T. inkin, the
      etiological agent of white piedra and trichosporonosis.

PMID- 25958331
TI  - [Management of neuropathic pain].
AB  - Neuropathic pain is often underestimated and not adequately treated. The DN4
      scale is very useful for its identification since it will benefit from
      pharmacological and non-pharmacological specific alternative care. The
      pathophysiological mechanisms involve the hyperexcitability of nociceptive
      pathways or decreased inhibitory descending controls that will be the target of
      pharmacological treatments. Frontline molecules are antidepressants (tricyclics
      and mixed serotonin and norepinephrine reuptake inhibitors) and antiepileptics
      (alpha2delta calcium channel inhibitors). However, these drugs will only have a
      partial efficacy on pain. The therapeutic strategy is based on reasonable goals,
      starting with a monotherapy adapted to the patient's symptoms and comorbidities
      and increased step by step. Patient compliance to contract is essential and
      requires clear and complete information. The impact on profession, social and
      family integration should rapidly be taken into account. In case of inefficiency,
      a change of the first-line treatment or an association could be considered. Some
      indications justify a specific therapy. Patients with resistant chronic pain
      should be sent to a specialized centre. New drugs are being studied and non
      pharmacological support must be evaluated. 

PMID- 25958330
TI  - The interfascicular matrix enables fascicle sliding and recovery in tendon, and
      behaves more elastically in energy storing tendons.
AB  - While the predominant function of all tendons is to transfer force from muscle to
      bone and position the limbs, some tendons additionally function as energy stores,
      reducing the cost of locomotion. Energy storing tendons experience extremely high
      strains and need to be able to recoil efficiently for maximum energy storage and
      return. In the equine forelimb, the energy storing superficial digital flexor
      tendon (SDFT) has much higher failure strains than the positional common digital
      extensor tendon (CDET). However, we have previously shown that this is not due to
      differences in the properties of the SDFT and CDET fascicles (the largest tendon
      subunits). Instead, there is a greater capacity for interfascicular sliding in
      the SDFT which facilitates the greater extensions in this particular tendon
      (Thorpe et al., 2012). In the current study, we exposed fascicles and
      interfascicular matrix (IFM) from the SDFT and CDET to cyclic loading followed by
      a test to failure. The results show that IFM mechanical behaviour is not a result
      of irreversible deformation, but the IFM is able to withstand cyclic loading, and
      is more elastic in the SDFT than in the CDET. We also assessed the effect of
      ageing on IFM properties, demonstrating that the IFM is less able to resist
      repetitive loading as it ages, becoming stiffer with increasing age in the SDFT.
      These results provide further indications that the IFM is important for efficient
      function in energy storing tendons, and age-related alterations to the IFM may
      compromise function and predispose older tendons to injury. 

PMID- 25958332
TI  - Aging increases microglial proliferation, delays cell migration, and decreases
      cortical neurogenesis after focal cerebral ischemia.
AB  - BACKGROUND: Aging is not just a risk factor of stroke, but it has also been
      associated with poor recovery. It is known that stroke-induced neurogenesis is
      reduced but maintained in the aged brain. However, there is no consensus on how
      neurogenesis is affected after stroke in aged animals. Our objective is to
      determine the role of aging on the process of neurogenesis after stroke. METHODS:
      We have studied neurogenesis by analyzing proliferation, migration, and formation
      of new neurons, as well as inflammatory parameters, in a model of cerebral
      ischemia induced by permanent occlusion of the middle cerebral artery in young-
      (2 to 3 months) and middle-aged mice (13 to 14 months). RESULTS: Aging increased
      both microglial proliferation, as shown by a higher number of BrdU(+) cells and
      BrdU/Iba1(+) cells in the ischemic boundary and neutrophil infiltration.
      Interestingly, aging increased the number of M1 monocytes and N1 neutrophils,
      consistent with pro-inflammatory phenotypes when compared with the alternative M2
      and N2 phenotypes. Aging also inhibited (subventricular zone) SVZ cell
      proliferation by decreasing both the number of astrocyte-like type-B (prominin
      1(+)/epidermal growth factor receptor (EGFR)(+)/nestin(+)/glial fibrillary acidic
      protein (GFAP)(+) cells) and type-C cells (prominin-1(+)/EGFR(+)/nestin(
      )/Mash1(+) cells), and not affecting apoptosis, 1 day after stroke. Aging also
      inhibited migration of neuroblasts (DCX(+) cells), as indicated by an
      accumulation of neuroblasts at migratory zones 14 days after injury;
      consistently, aged mice presented a smaller number of differentiated interneurons
      (NeuN(+)/BrdU(+) and GAD67(+) cells) in the peri-infarct cortical area 14 days
      after stroke. CONCLUSIONS: Our data confirm that stroke-induced neurogenesis is
      maintained but reduced in aged animals. Importantly, we now demonstrate that
      aging not only inhibits proliferation of specific SVZ cell subtypes but also
      blocks migration of neuroblasts to the damaged area and decreases the number of
      new interneurons in the cortical peri-infarct area. Thus, our results highlight
      the importance of using aged animals for translation to clinical studies.

PMID- 25958333
TI  - Sleep-disordered breathing and asthma: evidence from a large multicentric
      epidemiological study in China.
AB  - BACKGROUND: Previous studies have postulated that sleep-disordered breathing
      (SDB) may be associated with the occurrence and exacerbation of asthma. However,
      there was limited quantitative evidence on the topic. This study aimed at
      investigating the prevalence and predisposing factors of asthma, and quantifying
      the association between SDB and asthma among school-aged children in China. In
      addition, a comprehensive meta-analysis of the published evidences and our
      findings were further conducted. METHODS: To test the hypothesis, we conducted a
      multicentric cross-sectional study involving 22,478 children aged 5-12 years
      recruited from eight cities in China. Furthermore, a meta-analysis based on both
      previously published studies and our cross-sectional study was performed.
      RESULTS: The prevalence rate of SDB and asthma was 12.0% and 3.5% among our cross
      sectional study sample. It was demonstrated that symptoms of SDB, such as
      habitual snoring (OR = 1.28, 95%CI: 1.01-1.62), and obstructive sleep apnea (OSA)
      (OR = 1.92, 95%CI: 1.34-2.76), were significantly associated with asthma, after
      adjusting for potential confounding factors. In the meta-analysis, SDB was
      correlated with the prevalence of asthma in both children (OR = 1.58, 95%CI: 1.35
      1.80) and adults (OR = 1.55, 95%CI: 1.42-1.67). CONCLUSIONS: Our results provide
      further evidence for the independent association between SDB and asthma. The
      clinical significance of our findings lies in the emphasis that children
      undergoing examination or treatment for asthma should be routinely screened for
      sleep problems. Further systematic study is required to illuminate the underlying
      mechanism.

PMID- 25958334
TI  - Aging and Multimorbidity: New Tasks, Priorities, and Frontiers for Integrated
      Gerontological and Clinical Research.
AB  - Aging is characterized by rising susceptibility to development of multiple
      chronic diseases and, therefore, represents the major risk factor for
      multimorbidity. From a gerontological perspective, the progressive accumulation
      of multiple diseases, which significantly accelerates at older ages, is a
      milestone for progressive loss of resilience and age-related multisystem
      homeostatic dysregulation. Because it is most likely that the same mechanisms
      that drive aging also drive multiple age-related chronic diseases, addressing
      those mechanisms may reduce the development of multimorbidity. According to this
      vision, studying multimorbidity may help to understand the biology of aging and,
      at the same time, understanding the underpinnings of aging may help to develop
      strategies to prevent or delay the burden of multimorbidity. As a consequence, we
      believe that it is time to build connections and dialogue between the clinical
      experience of general practitioners and geriatricians and the scientists who
      study aging, so as to stimulate innovative research projects to improve the
      management and the treatment of older patients with multiple morbidities. 

PMID- 25958337
TI  - International Society for Cell Therapy Facility Sanitization Survey Laboratory
      Practices Committee Report.
AB  - BACKGROUND AIMS: Quality cell manufacturing processes require a clean laboratory
      environment. METHODS: This report was aimed at describing current cleaning and
      sanitization practices reported by facilities that manufacture many types of
      cellular therapy products for clinical use. It is our hope that this report may
      provide the groundwork for guidance recommendations directed at developing
      consensus standards for cleaning and sanitization practices across the globe.
      Facility sanitization is a central issue to regulatory and accreditation bodies.
      Facilities are required to develop plans to assess sanitization practices and
      test cleaning effectiveness. RESULTS: This document provides information on how
      this is performed in different facilities and may allow newer, smaller or less
      developed facilities to build, enhance or revise their current quality program by
      using experience and expertise in facility sanitization reported herein.
      CONCLUSIONS: This report summarizes the results of the latest survey and compares
      results with those previously reported. New and relevant trends in the field
      provide important information and will provide important information for
      establishing guidelines.

PMID- 25958336
TI  - A presequence-binding groove in Tom70 supports import of Mdl1 into mitochondria.
AB  - The translocase of the outer mitochondrial membrane (TOM complex) is the general
      entry gate into mitochondria for almost all imported proteins. A variety of
      specific receptors allow the TOM complex to recognize targeting signals of
      various precursor proteins that are transported along different import pathways.
      Aside from the well-characterized presequence receptors Tom20 and Tom22 a third
      TOM receptor, Tom70, binds proteins of the carrier family containing multiple
      transmembrane segments. Here we demonstrate that Tom70 directly binds to
      presequence peptides using a dedicated groove. A single point mutation in the
      cavity of this pocket (M551R) reduces the presequence binding affinity of Tom70
      ten-fold and selectively impairs import of the presequence-containing precursor
      Mdl1 but not the ADP/ATP carrier (AAC). Hence Tom70 contributes to the
      presequence import pathway by recognition of the targeting signal of the Mdl1
      precursor. 

PMID- 25958338
TI  - Confusing acceptance and mere politeness: Depression and sensitivity to Duchenne
      smiles.
AB  - BACKGROUND AND OBJECTIVES: Whereas the association between depression and the
      perception of emotions has been widely studied, only few studies have examined
      the association between depression and the ability to discriminate genuine
      (Duchenne) from fake (non-Duchenne) smiles. The present study examined this by
      comparing currently depressed, previously depressed, and healthy control
      individuals. Guided by recent theory, the present study also investigated the
      effect of depression recurrence on smile identification. METHODS: Participants
      were 27 healthy controls, 33 with past depression (51% with recurrent
      depression), and 22 with current depression (77% with recurrent depression).
      Participants were presented with a series of 20 videos depicting smiling
      individuals, and were asked to indicate whether each smile was genuine or fake.
      RESULTS: Having (or having had) a first episode of depression was associated with
      more mistakes in categorizing smiles as genuine or fake compared to having
      recurrent depression or to having no history of depression. LIMITATIONS: Cross
      sectional design and a (relatively) small sample size. CONCLUSIONS: Our results
      show that an impaired ability to differentiate between markers of affiliation and
      politeness is specific to first-episode depression, even after the depression has
      remitted.

PMID- 25958339
TI  - Clinical, neuropathological and radiological evidence for a rare complication of
      rituximab therapy.
AB  - We report a rare case of myofasciitis and meningitis with deafness caused by
      systemic enterovirus infection in the setting of hypogammaglobulinaemia induced
      by rituximab. Whilst effective and generally safe, anti- CD 20 antibody therapy
      is increasingly recognised to result in unusual infectious complications to be
      considered in a treated patient presenting with neurological symptoms. These
      cases may pose diagnostic difficulties and can have atypical presentations. We
      present this rare complication of rituximab therapy, with histopathological
      confirmation of myofasciitis. In the older literature, enterovirus associated
      myofasciitis may have erroneously been termed dermatomyositis and we review the
      literature to demonstrate this important nosological point. 

PMID- 25958335
TI  - Mechanical dynamics in live cells and fluorescence-based force/tension sensors.
AB  - Three signaling systems play the fundamental roles in modulating cell activities:
      chemical, electrical, and mechanical. While the former two are well studied, the
      mechanical signaling system is still elusive because of the lack of methods to
      measure structural forces in real time at cellular and subcellular levels.
      Indeed, almost all biological processes are responsive to modulation by
      mechanical forces that trigger dispersive downstream electrical and biochemical
      pathways. Communication among the three systems is essential to make cells and
      tissues receptive to environmental changes. Cells have evolved many sophisticated
      mechanisms for the generation, perception and transduction of mechanical forces,
      including motor proteins and mechanosensors. In this review, we introduce some
      background information about mechanical dynamics in live cells, including the
      ubiquitous mechanical activity, various types of mechanical stimuli exerted on
      cells and the different mechanosensors. We also summarize recent results obtained
      using genetically encoded FRET (fluorescence resonance energy transfer)-based
      force/tension sensors; a new technique used to measure mechanical forces in
      structural proteins. The sensors have been incorporated into many specific
      structural proteins and have measured the force gradients in real time within
      live cells, tissues, and animals. 

PMID- 25958340
TI  - Compound RYR1 heterozygosity resulting in a complex phenotype of malignant
      hyperthermia susceptibility and a core myopathy.
AB  - Malignant hyperthermia (MH) is a potentially fatal pharmacogenetic myopathy
      triggered by exposure to volatile anesthetics and/or depolarizing muscle
      relaxants. Susceptibility to MH is primarily associated with dominant mutations
      in the ryanodine receptor type 1 gene (RYR1). Recent genetic studies have shown
      that RYR1 variants are the most common cause of dominant and recessive congenital
      myopathies - central core and multi-minicore disease, congenital fiber type
      disproportion, and centronuclear myopathy. However, the MH status of many
      patients, especially with recessive RYR1-related myopathies, remains uncertain.
      We report the occurrence of a triplet of RYR1 variants, c.4711A>G (p.Ile1571Val),
      c.10097G>A (p.Arg3366His), c.11798A>G (p.Tyr3933Cys), found in cis in four
      unrelated families, one from Belgium, one from The Netherlands and two from
      Canada. Phenotype-genotype correlation analysis indicates that the presence of
      the triplet allele alone confers susceptibility to MH, and that the presence of
      this allele in a compound heterozygous state with the MH-associated RYR1 variant
      c.14545G>A (p.Val4849Ile) results in the MH susceptibility phenotype and a
      congenital myopathy with cores and rods. Our study underlines the notion that
      assigning pathogenicity to individual RYR1 variants or combination of variants,
      and counseling in RYR1-related myopathies may require integration of clinical,
      histopathological, in vitro contracture testing, MRI and genetic findings. 

PMID- 25958341
TI  - SIL1-related Marinesco-Sjoegren syndrome (MSS) with associated motor neuronopathy
      and bradykinetic movement disorder.
AB  - Marinesco-Sjoegren syndrome (MSS) is a recessively inherited multisystem disorder
      caused by mutations in SIL1 and characterized by cerebellar atrophy with ataxia,
      cataracts, a skeletal muscle myopathy, and variable degrees of developmental
      delay. Pathogenic mechanisms implicated to date include mitochondrial, nuclear
      envelope and lysosomal-autophagic pathway abnormalities. Here we present a 5-year
      old girl with SIL1-related MSS and additional unusual features of an associated
      motor neuronopathy and a bradykinetic movement disorder preceding the onset of
      ataxia. These findings suggest that an associated motor neuronopathy may be part
      of the phenotypical spectrum of SIL1-related MSS and should be actively
      investigated in genetically confirmed cases. The additional observation of a
      bradykinetic movement disorder suggests an intriguing continuum between
      neurodevelopmental and neurodegenerative multisystem disorders intricately linked
      in the same cellular pathways. 

PMID- 25958342
TI  - The complete title: The effect of interleukin-28B rs12979860 polymorphism on the
      therapeutic response of Moroccan patients with chronic hepatitis C.
AB  - BACKGROUND/AIMS: There is increasing evidence for the effect of rs12979860 IL28B
      polymorphism in response to the standard treatment PEG-IFN/RBV (i.e. combination
      of pegylated interferon and ribavirin) in chronic hepatitis C virus (HCV)
      infection. The present study aimed to determine the impact of IL28B associations
      in interferon responsiveness in 187 Moroccan patients with chronic HCV infection.
      METHODS: HCV RNA levels were measured with a real-time RT-PCR assay and treatment
      efficacy was assessed by sustained virological response (SVR) and patients were
      classified as responders or non-responders. IL28B rs12979860 polymorphism
      genotyping was achieved by PCR-HRM technique. RESULTS: The results demonstrated
      that SVR was achieved in 102 patients (55%); while 69 were non-responders (37%)
      and 16 relapsed (8%). Genotype 1 was the predominant HCV genotype detected in 112
      patients followed by genotype 2 in 56 patients. The genotype CC was observed in
      42 cases (25%); CT in 69 (41%) and TT in 57 (34%) demonstrating a C allele
      frequency of 46%. The SVR was observed in 32 patients with genotype CC accounting
      for 76%. The frequencies of rs12979860 CC type in infected individuals with HCV
      genotype 1 were 47% and 12% respectively in SVR and non-SVR groups. A highly
      statistically significant association between this SNP and SVR was found
      (p<0.001). Using multivariate logistic regression analysis, CC genotype was an
      independent factor for SVR. In the group of patients infected with genotype 2,
      SVR rate was 79%. The frequency of rs12979860 CC type in SVR group (n=4) was 9%
      and rs12979860 non-CC genotype was highly associated with SVR (p=0.001).
      CONCLUSION: This finding adds evidence that genotyping for the IL-28B rs12979860
      SNP can be a good parameter for the prediction of treatment success in patients
      with chronic hepatitis C before initiation of antiviral therapy in Morocco.

PMID- 25958343
TI  - Role of GTP-CHI links PAH and TH in melanin synthesis in silkworm, Bombyx mori.
AB  - In insects, pigment patterns are formed by melanin, ommochromes, and pteridines.
      Here, the effects of pteridine synthesis on melanin formation were studied using
      4th instar larvae of a wild-type silkworm strain, dazao (Bombyx mori), with
      normal color and markings. Results from injected larvae and in vitro integument
      culture indicated that decreased activity of guanosine triphosphate
      cyclohydrolase I (GTP-CH I, a rate-limiting enzyme for pteridine synthesis),
      lowers BH4 (6R-l-erythro-5,6,7,8-tetrahydrobiopterin, a production correlated
      with GTP-CH I activity) levels and eliminates markings and coloration. The
      conversion of phenylalanine and tyrosine to melanin was prevented when GTP-CH I
      was inhibited. When BH4 was added, phenylalanine was converted to tyrosine, and
      the tyrosine concentration increased. Tyrosine was then converted to melanin to
      create normal markings and coloration. Decreasing GTP-CH I activity did not
      affect L-DOPA (3,4-l-dihydroxyphenylalanine). GTP-CH I affected melanin synthesis
      by generating the BH4 used in two key reaction steps: (1) conversion of
      phenylalanine to tyrosine by PAH (phenylalanine hydroxylase) and (2) conversion
      of tyrosine to L-DOPA by TH (tyrosine hydroxylase). Expression profiles of
      BmGTPCH Ia, BmGTPCH Ib, BmTH, and BmPAH in the integument were consistent with
      the current findings. 

PMID- 25958344
TI  - A new SLC20A2 mutation identified in southern Italy family with primary familial
      brain calcification.
AB  - BACKGROUND: Primary familial brain calcification (PFBC) is a rare
      neurodegenerative disease characterized by bilateral calcifications mostly
      located in the basal ganglia and in the thalami, cerebellum and subcortical white
      matter. Clinical manifestations of this disease include a large spectrum of
      movement disorders and neuropsychiatric disturbances. PFBC is genetically
      heterogeneous and typically transmitted in an autosomal dominant fashion. Three
      causative genes have been reported: SLC20A2, PDGFRB and PDGFB. OBJECTIVE: We
      screened three PFBC Italian families for mutations in the SLC20A2, PDGFRB and
      PDGFB genes. METHODS: Phenotypic data were obtained by neurologic examination, CT
      scan and magnetic resonance imaging. Mutation screening of SLC20A2, PDGFRB and
      PDGFB was performed by sequencing. RESULTS: We identified a new heterozygous
      deletion c.21_21delG (p.L7Ffs*10) in SLC20A2 gene in one of these families. No
      mutations were detected in the other two families. CONCLUSIONS: Our data confirm
      that mutations in SLC20A2 are a major cause of familial idiopathic basal ganglia
      calcification.

PMID- 25958345
TI  - Expression of mouse Dab2ip transcript variants and gene methylation during brain
      development.
AB  - Dab2ip (DOC-2/DAB2 interacting protein) is a RasGAP protein which shows a growth
      inhibitory effect in human prostate cancer cell lines. Recent studies have shown
      that Dab2ip also plays an important role in regulating dendrite development and
      neuronal migration during brain development. In this study, we provide a more
      complete description of the mouse Dab2ip (mDab2ip) gene locus and examined DNA
      methylation and expression of Dab2ip during cerebellar development. Analysis of
      cDNA sequences in public databases revealed a total of 20 possible exons for
      mDab2ip gene, spanning over 172kb. Using Cap Analysis of Gene Expression (CAGE)
      data available through FANTOM5 project, we deduced five different transcription
      start sites for mDab2ip. Here, we characterized three different mDab2ip
      transcript variants beginning with exon 1. These transcripts varied by the
      presence or absence of exons 3 and 5, which encode a putative nuclear
      localization signal and the N-terminal region of a PH-domain, respectively. The
      5' region of the mDab2ip gene contains three putative CpG islands (CpG131, CpG54,
      and CpG85). Interestingly, CpG54 and CpG85 are localized on exons 3 and 5.
      Bisulfate DNA sequencing showed that methylation level of CpG54 remained constant
      whereas methylation of CpG85 increased during cerebellar development. Real-time
      PCR analysis showed that the proportion of PH-domain containing mDab2ip
      transcripts increased during cerebellar development, in correlation with the
      increase in CpG85 methylation. These data suggest that site-specific methylation
      of mDab2ip gene during cerebellar development may play a role in inclusion of
      exon 5, resulting in a Dab2ip transcript variant that encodes a full pleckstrin
      homology (PH) domain. 

PMID- 25958346
TI  - Correlation of functional GRIN2A gene promoter polymorphisms with schizophrenia
      and serum D-serine levels.
AB  - Schizophrenia is a severe, complex mental disorder. Abnormal glutamate
      neurotransmission mediated by decreased expression of N-methyl-d-aspartic acid
      receptors (NMDArs) and its endogenous co-agonist d-serine (d-Ser) has been
      proposed as one of the hypotheses of the pathogenesis of schizophrenia. GRIN2A
      gene promoter polymorphism causes changes in the regulation of the expression of
      NMDAr subunit genes. Our study is aimed at evaluating a possible association
      between GRIN2A promoter GT polymorphisms and schizophrenia in the Han Chinese
      population in Shaanxi and the relationship between serum d-Ser levels and GRIN2A
      (GT)n in schizophrenia. Four hundred and twenty patients with schizophrenia and
      410 healthy individuals were recruited in this study and GRIN2A (GT)n repeats as
      well as serum d-Ser levels were measured in all of the subjects. Nineteen alleles
      were found in (GT)n locus. The allele frequency of (GT)21, (GT)22 and (GT)23 in
      schizophrenic subjects was significantly lower compared with the mentally healthy
      controls, while the allele (GT)26 was significantly more frequent than in normal
      persons. Transcriptional activity of GRIN2A promoter was gradually suppressed
      with the increase in the length of the (GT)n repeats. d-Ser levels in the serum
      of the GRIN2A (GT)21 schizophrenic patients were significantly lower than those
      of the GRIN2A (GT)21 healthy control. A significant correlation between serum d
      Ser levels and GRIN2A (GT)21 in schizophrenia was detected. GRIN2A (GT)21 may
      play a significant role in the etiology of schizophrenia among the Chinese Han
      population of Shaanxi.

PMID- 25958347
TI  - Characterization of the interaction between superoxide dismutase and 2
      oxoisovalerate dehydrogenase.
AB  - Thermophiles are attractive microorganisms to study the adaptation of life in
      high temperature environment. It is revealed that superoxide dismutase (SOD) is
      essential for thermoadaptation of thermophiles. However, the SOD-mediated pathway
      of thermoadaptation remains unclear. To address this issue, the proteins
      interacted with SOD were characterized in Thermus thermophilus in this study.
      Based on co-immunoprecipitation and Western blot analyses, the results showed
      that 2-oxoisovalerate dehydrogenase alpha subunit was bound to SOD. The
      isothermal titration calorimetry analysis showed the existence of the interaction
      between SOD and 2-oxoisovalerate dehydrogenase alpha subunit. The bacterial two
      hybrid data indicated that SOD was directly interacted with 2-oxoisovalerate
      dehydrogenase alpha subunit. Gene site-directed mutagenesis analysis revealed
      that the intracellular interaction between SOD and 2-oxoisovalerate dehydrogenase
      alpha subunit was dependent on their whole molecules. Therefore our study
      presented a novel aspect of SOD in the thermoadaptation of thermophiles by
      interaction with dehydrogenase, a key enzyme of tricarboxylic acid cycle. 

PMID- 25958348
TI  - The sweet potato RbcS gene (IbRbcS1) promoter confers high-level and green tissue
      specific expression of the GUS reporter gene in transgenic Arabidopsis.
AB  - Sweet potato is an important crop because of its high yield and biomass
      production. We herein investigated the potential of the promoter activity of a
      small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (RbcS) from
      sweet potato (Ipomoea batatas) in order to develop the high expression system of
      exogenous DNA in Arabidopsis. We isolated two different cDNAs (IbRbcS1 and
      IbRbcS2) encoding RbcS from sweet potato. Their predicted amino acid sequences
      were well conserved with the mature RbcS protein of other plants. The tissue
      specific expression patterns of these two genes revealed that expression of
      IbRbcS1 was specific to green tissue, whereas that of IbRbcS2 was non
      photosynthetic tissues such as roots and tubers. These results suggested that
      IbRbcS1 was predominantly expressed in the green tissue-specific of sweet potato
      over IbRbcS2. Therefore, the IbRbcS1 promoter was transformed into Arabidopsis
      along with beta-glucuronidase (GUS) as a reporter gene. GUS staining and semi
      quantitative RT-PCR showed that the IbRbcS1 promoter conferred the expression of
      the GUS reporter gene in green tissue-specific and light-inducible manners.
      Furthermore, qPCR showed that the expression levels of GUS reporter gene in
      IbRbcS1 pro:GUS were same as those in CaMV 35S pro:GUS plants. These results
      suggest that the IbRbcS1 promoter is a potentially strong foreign gene expression
      system for genetic transformation in plants. 

PMID- 25958349
TI  - Association of the Ala16Val MnSOD gene polymorphism with plasma leptin levels and
      oxidative stress biomarkers in obese patients.
AB  - Chronic oxidative stress is a major characteristic of obesity. Manganese
      superoxide dismutase (MnSOD) is an antioxidant enzyme known to be present within
      mitochondria and is considered a main defense against oxidative stress. The aim
      of this study was to investigate the association between the MnSOD gene Ala16Val
      polymorphism in obesity in terms of body mass index (BMI), lipid parameters,
      plasma leptin levels, homeostasis model assessment of insulin resistance (HOMA
      IR), and oxidative stress biomarkers. The study included 150 obese and 120 non
      obese subjects. The MnSOD Ala16Val polymorphism was determined by polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP). Plasma leptin
      levels, serum lipid, superoxide dismutase (SOD), malondialdehyde (MDA), and
      anthropometric parameters were measured. No association was found between the
      MnSOD gene Ala16Val polymorphism and BMI in the study or control group.
      Strikingly, in the study group, obese subjects with the VV genotype had
      significantly higher plasma leptin levels (p<0.001) than those with the AA and AV
      genotypes. Serum total cholesterol (p<0.01) and MDA (p<0.001) levels were
      significantly higher in subjects with the VV genotype for MnSOD in the obese and
      non-obese groups. In the obese group, subjects with the VV genotype had
      significantly lower SOD (p<0.001) activity than the AA and AV genotypes. Our
      results suggest that the MnSOD gene polymorphism was associated with leptin
      levels and superoxide dismutase activity in the obese group but had no direct
      association with obesity. Moreover, the Ala16Val polymorphism has a significant
      effect on lipid profiles and MDA levels in both obese and non-obese subjects. 

PMID- 25958350
TI  - Molecular cloning and characterization of annexin genes in peanut (Arachis
      hypogaea L.).
AB  - Annexin, Ca(2+) or phospholipid binding proteins, with many family members are
      distributed throughout all tissues during plant growth and development. Annexins
      participate in a number of physiological processes, such as exocytosis, cell
      elongation, nodule formation in legumes, maturation and stress response. Six
      different full-length cDNAs and two partial-length cDNAs of peanut, (AnnAh1,
      AnnAh2, AnnAh3, AnnAh5, AnnAh6, AnnAh7, AnnAh4 and AnnAh8) encoding annexin
      proteins, were isolated and characterized using a RT-PCR/RACE-PCR based strategy.
      The predicted molecular masses of these annexins were 36.0kDa with acidic pIs of
      5.97-8.81. ANNAh1, ANNAh2, ANNAh3, ANNAh5, ANNAh6 and ANNAh7 shared sequence
      similarity from 35.76 to 66.35% at amino acid level. Phylogenetic analysis
      revealed their evolutionary relationships with corresponding orthologous
      sequences in soybean and deduced proteins in various plant species. Real-time
      quantitative assays indicated that these genes were differentially expressed in
      various organs. Transcript level analysis for six annexin genes under stress
      conditions showed that these genes were regulated by drought, salinity, heavy
      metal stress, low temperature and hormone. Additionally, the prediction of cis
      regulatory element suggested that different cis-responsive elements including
      stress- and hormone-responsive-related elements could respond to various stress
      conditions. These results indicated that members of AnnAhs family may play
      important roles in the adaptation of peanut to various environmental stresses.

PMID- 25958351
TI  - Transcriptomic analysis provides insight into high-altitude acclimation in
      domestic goats.
AB  - Domestic goats are distributed in a wide range of habitats and have acclimated to
      their local environmental conditions. To investigate the gene expression changes
      of goats that are induced by high altitude stress, we performed RNA-seq on 27
      samples from the three hypoxia-sensitive tissues (heart, lung, and skeletal
      muscle) in three indigenous populations from distinct altitudes (600 m, 2000 m,
      and 3000 m). We generated 129Gb of high-quality sequencing data (~4Gb per sample)
      and catalogued the expression profiles of 12,421 annotated hircine genes in each
      sample. The analysis showed global similarities and differences of high-altitude
      transcriptomes among populations and tissues as well as revealed that the heart
      underwent the most high-altitude induced expression changes. We identified
      numerous differentially expressed genes that exhibited distinct expression
      patterns, and nonsynonymous single nucleotide variant-containing genes that were
      highly differentiated between the high- and low-altitude populations. These genes
      have known or potential roles in hypoxia response and were enriched in functional
      gene categories potentially responsible for high-altitude stress. Therefore, they
      are appealing candidates for further investigation of the gene expression and
      associated regulatory mechanisms related to high-altitude acclimation.

PMID- 25958352
TI  - Levetiracetam synergises with common analgesics in producing antinociception in a
      mouse model of painful diabetic neuropathy.
AB  - Painful diabetic neuropathy is difficult to treat. Single analgesics often have
      insufficient efficacy and poor tolerability. Combination therapy may therefore be
      of particular benefit, because it might provide optimal analgesia with fewer
      adverse effects. This study aimed to examine the type of interaction between
      levetiracetam, a novel anticonvulsant with analgesic properties, and commonly
      used analgesics (ibuprofen, aspirin and paracetamol) in a mouse model of painful
      diabetic neuropathy. Diabetes was induced in C57BL/6 mice with a single high dose
      of streptozotocin, applied intraperitoneally (150 mg/kg). Thermal (tail-flick
      test) and mechanical (electronic von Frey test) nociceptive thresholds were
      measured before and three weeks after diabetes induction. The antinociceptive
      effects of orally administered levetiracetam, analgesics, and their combinations
      were examined in diabetic mice that developed thermal/mechanical
      hypersensitivity. In combination experiments, the drugs were co-administered in
      fixed-dose fractions of single drug ED50 and the type of interaction was
      determined by isobolographic analysis. Levetiracetam (10-100 mg/kg), ibuprofen (2
      50 mg/kg), aspirin (5-75 mg/kg), paracetamol (5-100 mg/kg), and levetiracetam
      analgesic combinations produced significant, dose-dependent antinociceptive
      effects in diabetic mice in both tests. In the tail-flick test, isobolographic
      analysis revealed 15-, and 19-fold reduction of doses of both drugs in the
      combination of levetiracetam with aspirin/ibuprofen, and paracetamol,
      respectively. In the von Frey test, approximately 7- and 9-fold reduction of
      doses of both drugs was detected in levetiracetam-ibuprofen and levetiracetam
      aspirin/levetiracetam-paracetamol combinations, respectively. These results show
      synergism between levetiracetam and ibuprofen/aspirin/paracetamol in a model of
      painful diabetic neuropathy and might provide a useful approach to the treatment
      of patients suffering from painful diabetic neuropathy.

PMID- 25958353
TI  - MicroRNA-based therapy and breast cancer: A comprehensive review of novel
      therapeutic strategies from diagnosis to treatment.
AB  - MicroRNAs (miRNA) are 21-23 nucleotide molecules not translated into proteins
      that bind and target the 3' untranslated regions of mRNA. These characteristics
      make them a possible tool for inhibiting protein translation. Different cellular
      pathways involved in cancer development, such as cellular proliferation,
      apoptosis, and migration, are regulated by miRNAs. The objective of this review
      is to discuss various miRNAs involved in breast cancer in detail as well as
      different therapeutic strategies from the clinic to industry. A comprehensive
      discussion is provided on various miRNAs involved in breast cancer development,
      progression, and metastasis as well as the roles, targets, and related
      therapeutic strategies of different miRNAs associated with breast cancer. miRNAs
      known to be clinically useful for the diagnosis and prognosis of breast cancer
      are also discussed. Different strategies and challenges, including nucleic acid
      based (miRNA mimics, antagomiRs, and miRNA sponges) and drug-based (drug
      resistance, drugs/miRNA interaction, nanodelivery, and sensing systems)
      approaches to suppress specific oncogenes and/or activate target tumor
      suppressors are discussed. In contrast to other articles written on the same
      topic, this review focuses on the therapeutic and clinical value of miRNAs as
      well as their corresponding targets in order to explore how these strategies can
      overcome breast cancer, which is the second most frequent type of cancer
      worldwide. This review focuses on promising and validated miRNAs involved in
      breast cancer. In particular, two miRNAs, miR-21 and miR-34, are discussed as the
      most promising targets for RNA-based therapy in non-invasive and invasive breast
      cancer, respectively. Finally, relevant and commercialized therapeutic strategies
      are highlighted. 

PMID- 25958354
TI  - Reconstruction of a glacial lake outburst flood (GLOF) in the Engano Valley,
      Chilean Patagonia: Lessons for GLOF risk management.
AB  - Floods from moraine-dammed lake failures can have long standing effects not only
      on riverine landscapes but also on mountain communities due to the high intensity
      (i.e. great depth and high velocities) and damaging capacity of glacial lake
      outburst floods (GLOFs). GLOFs may increase in frequency as glaciers retreat and
      new lakes develop and there is an urgent need to better understand GLOF dynamics
      and the measures required to reduce their negative outcomes. In Patagonia at
      least 16 moraine-dammed lakes have failed in historic time, however, data about
      GLOF dynamics and impacts in this region are limited. We reconstruct a GLOF that
      affected a small village in Chilean Patagonia in March 1977, by semi structured
      interviews, interpretation of satellite images and 2D hydraulic modelling. This
      provides insight into the GLOF dynamics and the planning issues that led to
      socioeconomic consequences, which included village relocation. Modelling shows
      that the water released by the GLOF was in the order of 12-13 * 10(6)m(3) and the
      flood lasted for about 10h, reaching a maximum depth of ~1.5m in Bahia Murta
      Viejo, ~ 26 km from the failed lake. The lake had characteristics in common with
      failed lakes worldwide (e.g. the lake was in contact with a retreating glacier
      and was dammed by a narrow-steep moraine). The absence of land-use planning and
      the unawareness of the GLOF hazard contributed to the village flooding. The Rio
      Engano GLOF illustrates how small-scale and short-distance migration is a
      reasonable coping strategy in response to a natural hazard that may increase in
      frequency as atmospheric temperature rises and glaciers retreat.

PMID- 25958355
TI  - Stable isotopes reveal sources of precipitation in the Qinghai Lake Basin of the
      northeastern Tibetan Plateau.
AB  - The use of isotopic tracers is an effective approach for characterizing the
      moisture sources of precipitation in cold and arid regions, especially in the
      Tibetan Plateau (TP), an area of sparse human habitation with few weather and
      hydrological stations. This study investigated stable isotope characteristics of
      precipitation in the Qinghai Lake Basin, analyzed moisture sources using data
      sets from NCEP-NCAR, and calculated vapor contributions from lake evaporation to
      the precipitation in the basin using a two-component mixing model. Results showed
      that the Local Meteoric Water Line (LMWL) was defined as delta(2)H=7.86
      delta(18)O+15.01, with a slope of less than 8, indicating that some non
      equilibrium evaporation processes occurred when the drops fell below the cloud
      base. Temperature effects controlled delta(18)O and delta(2)H in precipitation in
      the basin, with high values in summer season and low values in winter season.
      Moisture in the basin was derived predominantly from the Southeast Asian Monsoon
      (SEAM) from June to August and the Westerly Circulation (WC) from September
      through May. Meanwhile, the transition in atmospheric circulation took place in
      June and September. The SEAM strengthened gradually, while the WC weakened
      gradually in June, and inversely in September. However, the Southwest Asian
      Monsoon (SWAM) did not reach the Qinghai Lake Basin due to the barrier posed by
      Tanggula Mountain. High d-excess (>10 0/00) and significant altitude and lake
      effects of delta(18)O in precipitation suggested that the vapor evaporated from
      Qinghai Lake, strongly influenced annual precipitation, and affected the regional
      water cycle in the basin distinctly. The monthly contribution of lake evaporation
      to basin precipitation ranged from 3.03% to 37.93%, with an annual contribution
      of 23.42% or 90.54 mm, the majority of which occurred in the summer season. The
      findings demonstrate that the contribution of evaporation from lakes to
      atmospheric vapor is fundamental to water cycling on the TP.

PMID- 25958356
TI  - Potential PM2.5 impacts of festival-related burning and other inputs on air
      quality in an urban area of southern Taiwan.
AB  - The Mid-Autumn Festival (MAF), or Moon Festival, is a harvest festival in Taiwan,
      celebrated by families across the island with evening barbecues outside. This
      study investigated the potential impact of these activities on the air quality in
      Tainan, a city in southern Taiwan. Fine particulate matter (PM2.5) was examined
      in the period leading up to the MAF (pre-MAF), during the Festival (MAF), after
      the Festival (post-MAF), and in the period after this (a period of moderate air
      quality: MAQ). Gaseous pollutants in PM2.5 were, from highest to lowest mean
      concentration, NH3, SO2, HCl, HNO3, HNO2, and oxalic acid, while inorganic salts
      were mainly in the form of the photochemical products SO4(2-), NH4(+), and NO3(
      ). These inorganic salts accounted for 37.6%-44.5% of the PM2.5 mass
      concentration, while a further 26.3%-42.8% of the PM2.5 mass was total carbon
      (TC). TC was mostly composed of organic carbon (OC) produced by photochemical
      reactions. Of this, 9.8%-14.9% was carboxylates, of which oxalate was the most
      abundant compound, accounting for 22.8%-31.9% of carboxylates. The presence of
      phthalates in the PM2.5 indicated emissions from the plastics industry. Although
      a noticeable amount of aerosol was produced by festival activities and burning of
      softwood and hardwood, onshore air currents during the festival prevented
      potential high aerosol loading. During the moderate air quality period following
      post-MAF, the concentration of total carbohydrates was 1.44-2.64 times the amount
      during the festival. Levoglucosan and myo-inositol accounted for 81.7%-89.6% of
      the total carbohydrate concentration. The average Levo/Manno ratio was 18.64 +/-
      5.24. The concentration of levoglucosan was closely related to that of PO4(3-),
      erythritol, and galactose. Backward trajectories indicated that biomass burning
      in China affected the air quality of Tainan City.

PMID- 25958357
TI  - Searching for solutions to mitigate greenhouse gas emissions by agricultural
      policy decisions--Application of system dynamics modeling for the case of Latvia.
AB  - European Union (EU) Member States have agreed to limit their greenhouse gas (GHG)
      emissions from sectors not covered by the EU Emissions Trading Scheme (non-ETS).
      That includes also emissions from agricultural sector. Although the
      Intergovernmental Panel on Climate Change (IPCC) has established a methodology
      for assessment of GHG emissions from agriculture, the forecasting options are
      limited, especially when policies and their interaction with the agricultural
      system are tested. Therefore, an advanced tool, a system dynamics model, was
      developed that enables assessment of effects various decisions and measures have
      on agricultural GHG emissions. The model is based on the IPCC guidelines and
      includes the main elements of an agricultural system, i.e. land management,
      livestock farming, soil fertilization and crop production, as well as feedback
      mechanisms between the elements. The case of Latvia is selected for simulations,
      as agriculture generates 22% of the total anthropogenic GHG emissions in the
      country. The results demonstrate that there are very limited options for GHG
      mitigation in the agricultural sector. Thereby, reaching the non-ETS GHG emission
      targets will be very challenging for Latvia, as the level of agricultural GHG
      emissions will be exceeded considerably above the target levels. Thus, other non
      ETS sectors will have to reduce their emissions drastically to "neutralize" the
      agricultural sector's emissions for reaching the EU's common ambition to move
      towards low-carbon economy. The developed model may serve as a decision support
      tool for impact assessment of various measures and decisions on the agricultural
      system's GHG emissions. Although the model is applied to the case of Latvia, the
      elements and structure of the model developed are similar to agricultural systems
      in many countries. By changing numeric values of certain parameters, the model
      can be applied to analyze decisions and measures in other countries. 

PMID- 25958358
TI  - Arbuscular mycorrhizal fungal inoculation protects Miscanthus * giganteus against
      trace element toxicity in a highly metal-contaminated site.
AB  - Arbuscular mycorrhizal fungus (AMF)-assisted phytoremediation could constitute an
      ecological and economic method in polluted soil rehabilitation programs. The aim
      of this work was to characterize the trace element (TE) phytoremediation
      potential of mycorrhizal Miscanthus * giganteus. To understand the mechanisms
      involved in arbuscular mycorrhizal symbiosis tolerance to TE toxicity, the fatty
      acid compositions and several stress oxidative biomarkers were compared in the
      roots and leaves of Miscanthus * giganteus cultivated under field conditions in
      either TE-contaminated or control soils. TEs were accumulated in greater amounts
      in roots, but the leaves were the organ most affected by TE contamination and
      were characterized by a strong decrease in fatty acid contents. TE-induced
      oxidative stress in leaves was confirmed by an increase in the lipid peroxidation
      biomarker malondialdehyde (MDA). TE contamination decreased the GSSG/GSH ratio in
      the leaves of exposed plants, while peroxidase (PO) and superoxide dismutase
      (SOD) activities were increased in leaves and in whole plants, respectively. AMF
      inoculation also increased root colonization in the presence of TE contamination.
      The mycorrhizal colonization determined a decrease in SOD activity in the whole
      plant and PO activities in leaves and induced a significant increase in the fatty
      acid content in leaves and a decrease in MDA formation in whole plants. These
      results suggested that mycorrhization is able to confer protection against
      oxidative stress induced by soil pollution. Our findings suggest that mycorrhizal
      inoculation could be used as a bioaugmentation technique, facilitating Miscanthus
      cultivation on highly TE-contaminated soil.

PMID- 25958359
TI  - Characterization of PAHs and metals in indoor/outdoor PM10/PM2.5/PM1 in a
      retirement home and a school dormitory.
AB  - In the present work, we investigated the characteristics of polycyclic aromatic
      hydrocarbons (PAHs) and metal(loid)s in indoor/outdoor PM10, PM2.5, and PM1 in a
      retirement home and a school dormitory in Tehran from May 2012 to May 2013. The
      results indicated that the annual levels of indoor and outdoor PM10 and PM2.5
      were much higher than the guidelines issued by the World Health Organization
      (WHO). The most abundant detected metal(loid)s in PM were Si, Fe, Zn, Al, and Pb.
      We found higher percentages of metal(loid)s in smaller size fractions of PM.
      Additionally, the results showed that the total PAHs (?PAHs) bound to PM were
      predominantly (83-88%) found in PM2.5, which can penetrate deep into the alveolar
      regions of the lungs. In general, carcinogenic PAHs accounted for 40-47% of the
      total PAHs concentrations; furthermore, the smaller the particle size, the higher
      the percentage of carcinogenic PAHs. The percentages of trace metal(loid)s and
      carcinogenic PAHs in PM2.5 mass were almost twice as high as those in PM10. This
      can most likely be responsible for the fact that PM2.5 can cause more adverse
      health effects than PM10 can. The average BaP-equivalent carcinogenic (BaP-TEQ)
      levels both indoors and outdoors considerably exceeded the maximum permissible
      risk level of 1 ng/m(3) of BaP. The enrichment factors and diagnostic ratios
      indicated that combustion-related anthropogenic sources, such as gasoline- and
      diesel-fueled vehicles as well as natural gas combustion, were the major sources
      of PAHs and trace metal(loid)s bound to PM.

PMID- 25958360
TI  - Estimating the inhaled dose of pollutants during indoor physical activity.
AB  - BACKGROUND: It is undeniable that many benefits come from physical activity.
      People exercise in fitness centers to improve their health and well-being,
      prevent disease and to increase physical attractiveness. However, these
      facilities join conditions that cause poor indoor air quality. Moreover,
      increased inhalation rates during exercise have influence on inhaled doses of air
      pollution. OBJECTIVES: This study aims to calculate the inhaled dose of air
      pollutants during exercise, by estimating minute ventilation of participants and
      measuring air pollutant concentrations in fitness centers. METHODS: Firstly, the
      20 participants performed an incremental test on a treadmill, where heart rate
      and minute ventilation were measured simultaneously to develop individual
      exponential regression equations. Secondly, heart rate was measured during
      fitness classes and minute ventilation was estimated based on the calculated
      regression coefficients. Finally, the inhaled dose of air pollutants was
      calculated using the estimated minute ventilation and the concentrations of the
      pollutants measured in a monitoring program performed in 63 fitness classes.
      RESULTS: Estimated inhaled doses were higher in aerobic classes than in holistic
      classes. The main difference was registered for PM10 inhaled dose that presented
      an average ratio between aerobic and holistic classes greater than four. Minute
      ventilation and PM10 concentrations in aerobic classes were, on average, 2.0
      times higher than in holistic classes. Results showed that inhalation of
      pollutants is increased during heavy exercise, demonstrating the need to maintain
      high indoor air quality in fitness centers. CONCLUSIONS: This study illustrates
      the importance of inclusion minute ventilation data when comparing inhaled doses
      of air pollution between different population groups. This work has estimated for
      the first time the minute ventilation for different fitness classes. Also
      constitutes an important contribution for the assessment of inhaled dose in
      future studies to be performed in fitness centers.

PMID- 25958361
TI  - Disaggregating the contribution of local dispersion and long-range transport to
      the high PM10 values measured in a Mediterranean urban environment.
AB  - The EU daily PM10 limit-value of 50 MUg m(-3) is frequently breached in the
      center of Athens, Greece. A total of 852 daily exceedances were recorded in the
      city-center during the 6-year period 2001-2006. These exceedances were more
      frequent in winter, followed by spring and autumn. For the needs of the study,
      the PM10 episodes (i.e., concentrations 30% above the median value) were grouped
      in two categories: (a) the City-Center episodes and (b) the Wider Metropolitan
      Area episodes. It was assumed that City-Center episodes occurred when elevated
      PM10 values were measured in the city-center exclusively, whereas Wider
      Metropolitan Area episodes occurred when high PM10 concentrations were also
      measured in the suburbs. Then back-trajectory cluster analysis was performed in
      an attempt to associate high PM10 levels with local dispersion or long-range
      transport. The City-Center episodes were associated according to the origin of
      air parcels with six types of air-masses (slow and fast moving from northern,
      northeasterly and southern directions, or stagnated around Athens) and were
      mainly due to traffic or other local sources, whereas the Wider Metropolitan Area
      episodes were mainly associated with air-masses coming from southern directions
      and were linked to long-range transport. On the whole, the analysis provided
      evidence of Sahara-dust events and sea-spray transportation.

PMID- 25958362
TI  - Co-addition of manure increases the dissipation rates of tylosin A and the
      numbers of resistance genes in laboratory incubation experiments.
AB  - The behavior of veterinary antibiotics in the soil is commonly studied using the
      following methods to add antibiotics to the soil: (A) adding manure collected
      from animals fed a diet that includes antibiotics; (B) adding antibiotic-free
      animal manure spiked with antibiotics; and (C) the direct addition of
      antibiotics. However, most studies have only used methods (B) and (C) in their
      research, and few studies have simultaneously compared the different antibiotic
      addition methods. This study used tylosin A (TYLA) as a model antibiotic to
      compare the effects of these three commonly used antibiotic addition methods on
      the dissipation rates of TYLA and the numbers of resistance genes in laboratory
      incubation experiments. The results showed that the three treatment methods
      produced similar TYLA degradation trends; however, there were significant
      differences (P<0.05) in the TYLA degradation half-life (t1/2) among the three
      methods. The half-life of TYLA degradation in treatments A, B and C was 2.44 +/-
      0.04, 1.21 +/- 0.03 and 5.13 +/- 0.11 days, respectively. The presence of manure
      resulted in a higher electrical conductivity (EC), higher relative abundance of
      Citrobacter amalonaticus, higher macrolide resistant gene (ermB, ermF and ermT)
      count and lower ecological toxicity in the soil, which could partially explain
      the higher TYLA degradation rate in the treatments containing manure. The higher
      degradation rate of TYLA in treatment B when compared to treatment A could be due
      to the lower concentrations of tylosin B (TYLB) and tylosin D (TYLD). The main
      route for veterinary antibiotics to enter the soil is via the manure of animals
      that have been administered antibiotics. Therefore, the more appropriate method
      to study the degradation and ecotoxicity of antibiotic residues in the soil is by
      using manure from animals fed/administered the particular antibiotic rather than
      by adding the antibiotic directly to the soil.

PMID- 25958363
TI  - Combining visible-based-color parameters and geochemical tracers to improve
      sediment source discrimination and apportionment.
AB  - Parameter selection in fingerprinting studies are often time-consuming and costly
      because successful fingerprint properties are generally highly site-specific.
      Recently, spectroscopy has been applied to trace sediment origin as a rapid, less
      expensive, non-destructive and straightforward alternative. We show in this study
      the first attempt to combine both geochemical tracers and color parameters
      derived from the visible (VIS) spectrum in a single estimate of sediment source
      contribution. Moreover, we compared the discrimination power and source
      apportionment using VIS-based-color parameters and using the whole ultra-violet
      visible (UV-VIS) spectrum in partial last square regression (PLSR) models. This
      study was carried out in a small (1.19 km(2)) rural catchment from southern
      Brazil. The sediment sources evaluated were crop fields, unpaved roads, and
      stream channels. Color parameters were only able to discriminate unpaved roads
      from the other sources, disabling its use to fingerprint sediment sources itself.
      Nonetheless, there was a great improvement in source discrimination combining
      geochemical tracers and color parameters. Unlike VIS-based-color parameters, the
      distances between sediment sources were always significantly different using the
      whole UV-VIS-spectrum. It indicates a loss of information and, consequently, loss
      of discriminating power when using VIS-based-color parameters instead of the
      whole UV-VIS spectrum. Overall, there was good agreement in source ascription
      obtained with geochemical tracers alone, geochemical tracers coupled with color
      parameters, and UV-VIS-PLSR models, and all of them indicate clearly that the
      main sediment source was the crop fields, corresponding to 57 +/- 14, 48 +/- 13,
      and 62 +/- 18%, respectively. Prediction errors for UV-VIS-PLSR models (6.6 +/-
      1.1%) were very similar to those generated in a mixed linear model using
      geochemical tracers alone (6.4 +/- 3.6%), but the combination of color parameters
      and geochemical tracers decreases the prediction error (5.4 +/- 2.0%). Therefore,
      the use of VIS-based-color parameters combined to geochemical tracers can be a
      rapid and inexpensive way to improve source discrimination and precision of
      sediment source apportionment.

PMID- 25958364
TI  - Sources of atmospheric aerosol from long-term measurements (5 years) of chemical
      composition in Athens, Greece.
AB  - To identify the sources of aerosols in Greater Athens Area (GAA), a total of 1510
      daily samples of fine (PM 2.5) and coarse (PM 10-2,5) aerosols were collected at
      a suburban site (Penteli), during a five year period (May 2008-April 2013)
      corresponding to the period before and during the financial crisis. In addition,
      aerosol sampling was also conducted in parallel at an urban site (Thissio),
      during specific, short-term campaigns during all seasons. In all these samples
      mass and chemical composition measurements were performed, the latest only at the
      fine fraction. Particulate organic matter (POM) and ionic masses (IM) are the
      main contributors of aerosol mass, equally contributing by accounting for about
      24% of the fine aerosol mass. In the IM, nss-SO4(-2) is the prevailing specie
      followed by NO3(-) and NH4(+) and shows a decreasing trend during the 2008-2013
      period similar to that observed for PM masses. The contribution of water in fine
      aerosol is equally significant (21 +/- 2%), while during dust transport, the
      contribution of dust increases from 7 +/- 2% to 31 +/- 9%. Source apportionment
      (PCA and PMF) and mass closure exercises identified the presence of six sources
      of fine aerosols: secondary photochemistry, primary combustion, soil, biomass
      burning, sea salt and traffic. Finally, from winter 2012 to winter 2013 the
      contribution of POM to the urban aerosol mass is increased by almost 30%,
      reflecting the impact of wood combustion (dominant fuel for domestic heating) to
      air quality in Athens, which massively started in winter 2013.

PMID- 25958365
TI  - Organic matter breakdown in streams in a region of contrasting anthropogenic land
      use.
AB  - Streams provide ecosystem services to humans that depend on ecosystem functions,
      such as organic matter breakdown (OMB). OMB can be affected by land use-related
      disturbance. We measured OMB in 29 low-order streams in a region of contrasting
      land use in south-west Germany to quantify land use effects on OMB. We deployed
      fine and coarse mesh leaf bags in streams of forest, agricultural, vinicultural
      and urban catchments to determine the microbial and invertebrate-mediated OMB,
      respectively. Furthermore, we monitored physicochemical, geographical and habitat
      parameters to explain potential differences in OMB among land use types and
      sites. Only microbial OMB differed between land use types. Microbial OMB was
      negatively correlated with pH and invertebrate-mediated OMB was positively
      correlated with tree cover. Generally, OMB responded to stressor gradients rather
      than directly to land use. Therefore, the monitoring of specific stressors may be
      more relevant than land use to detect effects on ecosystem functions, and to
      extrapolate effects on functions, e.g. in the context of assessing ecosystem
      services. 

PMID- 25958366
TI  - Modelling atmospheric oxidation of 2-aminoethanol (MEA) emitted from post
      combustion capture using WRF-Chem.
AB  - Carbon capture and storage (CCS) is a technological solution that can reduce the
      amount of carbon dioxide (CO2) emissions from the use of fossil fuel in power
      plants and other industries. A leading method today is amine based post
      combustion capture, in which 2-aminoethanol (MEA) is one of the most studied
      absorption solvents. In this process, amines are released to the atmosphere
      through evaporation and entrainment from the CO2 absorber column. Modelling is a
      key instrument for simulating the atmospheric dispersion and chemical
      transformation of MEA, and for projections of ground-level air concentrations and
      deposition rates. In this study, the Weather Research and Forecasting model
      inline coupled with chemistry, WRF-Chem, was applied to quantify the impact of
      using a comprehensive MEA photo-oxidation sequence compared to using a simplified
      MEA scheme. Main discrepancies were found for iminoethanol (roughly doubled in
      the detailed scheme) and 2-nitro aminoethanol, short MEA-nitramine (reduced by
      factor of two in the detailed scheme). The study indicates that MEA emissions
      from a full-scale capture plant can modify regional background levels of
      isocyanic acid. Predicted atmospheric concentrations of isocyanic acid were
      however below the limit value of 1 ppbv for ambient exposure. The dependence of
      the formation of hazardous compounds in the OH-initiated oxidation of MEA on
      ambient level of nitrogen oxides (NOx) was studied in a scenario without NOx
      emissions from a refinery area in the vicinity of the capture plant. Hourly MEA
      nitramine peak concentrations higher than 40 pg m(-3) did only occur when NOx
      mixing ratios were above 2 ppbv. Therefore, the spatial variability and temporal
      variability of levels of OH and NOx need to be taken into account in the health
      risk assessment. The health risk due to direct emissions of nitrosamines and
      nitramines from full-scale CO2 capture should be investigated in future studies.

PMID- 25958367
TI  - Mercury bioaccumulation in the food web of Three Gorges Reservoir (China): Tempo
      spatial patterns and effect of reservoir management.
AB  - Tempo-spatial patterns of mercury bioaccumulation and tropho-dynamics, and the
      potential for a reservoir effect were evaluated in the Three Gorges Reservoir
      (TGR, China) from 2011 to 2012, using total mercury concentrations (THg) and
      stable isotopes (delta(13)C and delta(15)N) of food web components (seston,
      aquatic invertebrates and fish). Hg concentrations in aquatic invertebrates and
      fish indicated a significant temporal trend associated with regular seasonal
      water-level manipulation. This includes water level lowering to allow for storage
      of water during the wet season (summer); a decrease of water levels from
      September to June providing a setting for flood storage. Hg concentrations in
      organisms were the highest after flooding. Higher Hg concentrations in fish were
      observed at the location farthest from the dam. Hg concentrations in water and
      sediment were correlated. Compared with the reservoirs of United States and
      Canada, TGR had lower trophic magnification factors (0.046-0.066), that are
      explained primarily by organic carbon concentrations in sediment, and the effect
      of "growth dilution". Based on comparison before and after the impoundment of
      TGR, THg concentration in biota did not display an obvious long-term reservoir
      effect due to (i) short time since inundation, (ii) regular water discharge
      associated with water-level regulation, and/or (iii) low organic matter content
      in the sediment. 

PMID- 25958370
TI  - [Electronic system of Revista Alergia Mexico, a new challenge].

PMID- 25958369
TI  - Cross-cultural adaptation of the stroke action test for Italian--speaking people.
AB  - BACKGROUND: Assessing the level of public stroke awareness is a prerequisite for
      development of community educational campaigns aimed at reducing prehospital
      delay of stroke patients. The Stroke Action Test (STAT) is a validated instrument
      specifically developed in the United States with the objective to assess the
      public's readiness to respond to stroke. Our purpose was to perform the cross
      cultural adaptation of the original version of STAT to be applied to the Italian
      population. METHODS: The process of cross-cultural adaptation has been performed
      according to guidelines, intended for questionnaires of self-report health status
      measures, following five steps: forward translation, synthesis, back translation,
      approval by an Expert Committee and test of the pre-final version. For this last
      step, 31 adults were asked to rate each item in terms of adequacy of content,
      clarity of wording and usefulness, according to a 3-point scale. The final
      version has been administered to a sample of 202 volunteers to assess its
      acceptability and reliability in terms of the internal consistency. RESULTS: The
      pre-final version of the STAT was developed taking into accounts few and minimal
      discrepancies between the two back translations and the original version of the
      instrument. Most items were judged as adequate, easy to understand and useful,
      according to the frequency of high scores (>50 %) given by the adaptation sample.
      As for further testing of the adapted final version, completeness of item
      response was very good. Distribution of scores ranged from 0 to 100 %, without
      any floor or ceiling effect, with a percentage of the lowest scoring of 1.5 % for
      the 28-item test and 2.5 % for the 21-item test and a percentage of the highest
      scoring of 1 % for both tests. Internal consistency was high for both the 28-item
      and 21-item tests (Cronbach alpha = 0.85 and 0.84, respectively). CONCLUSIONS:
      The process used to perform the cross-cultural adaptation of the questionnaire
      was successful. The Italian version of STAT demonstrated good acceptability and
      psychometric properties and is now available to assess stroke awareness in
      Italian people.

PMID- 25958368
TI  - Marine ecotoxicity of nitramines, transformation products of amine-based carbon
      capture technology.
AB  - In the context of reducing CO2 emissions to the atmosphere, chemical absorption
      with amines is emerging as the most advanced technology for post-combustion CO2
      capture from exhaust gases of fossil fuel power plants. Despite amine solvent
      recycling during the capture process, degradation products are formed and
      released into the environment, among them aliphatic nitramines, for which the
      environmental impact is unknown. In this study, we determined the acute and
      chronic toxicity of two nitramines identified as important transformation
      products of amine-based carbon capture, dimethylnitramine and ethanolnitramine,
      using a multi-trophic suite of bioassays. The results were then used to produce
      the first environmental risk assessment for the marine ecosystem. In addition,
      the in vivo genotoxicity of nitramines was studied by adapting the comet assay to
      cells from experimentally exposed fish. Overall, based on the whole organism
      bioassays, the toxicity of both nitramines was considered to be low. The most
      sensitive response to both compounds was found in oysters, and dimethylnitramine
      was consistently more toxic than ethanolnitramine in all bioassays. The Predicted
      No Effect Concentrations for dimethylnitramine and ethanolnitramine were 0.08 and
      0.18 mg/L, respectively. The genotoxicity assessment revealed contrasting results
      to the whole organism bioassays, with ethanolnitramine found to be more genotoxic
      than dimethylnitramine by three orders of magnitude. At the lowest
      ethanolnitramine concentration (1mg/L), 84% DNA damage was observed, whereas
      100mg/L dimethylnitramine was required to cause 37% DNA damage. The mechanisms of
      genotoxicity were also shown to differ between the two compounds, with oxidation
      of the DNA bases responsible for over 90% of the genotoxicity of
      dimethylnitramine, whereas DNA strand breaks and alkali-labile sites were
      responsible for over 90% of the genotoxicity of ethanolnitramine. Fish exposed to
      >3mg/L ethanolnitramine had virtually no DNA left in their red blood cells.

PMID- 25958371
TI  - [Structural and functional heart diseases in adult patients with common variable
      immunodeficiency].
AB  - BACKGROUND: Common variable immunodeficiency (CVID) is the primary
      immunodeficiency with the largest number of comorbidities in adulthood. It has
      been associated with bronchiectasis between 17%-76%, and these with the presence
      of cardiovascular complications such as pulmonary hypertension and heart failure.
      The new image methods of diagnosis, to assess the cardiovascular structural and
      functional conformation of adult patients with bronchiectasis, help to establish
      more efficient and timely diagnoses. OBJECTIVE: To define the presence of
      structural and functional heart disease in CVID patients by transthoracic
      echocardiography. MATERIAL AND METHOD: A cross-sectional study was done in a
      cohort of 26 adult patients diagnosed with CVID and replacement therapy with
      intravenous immunoglobulin (IVIG), belonging to the Immunodeficiency Clinic. All
      patients underwent transthoracic echocardiography and tissue ECO doopler; the
      results were evaluated by a echocardiographer physician. RESULTS: We evaluated 26
      patients, of whom 10 patients were male, with a mean age of 35.7 +/- 13.7 years.
      The results of thoracic echocardiography of the left cardiac cavities found the
      following functional changes: 17 patients presented with mitral insufficiency and
      only 2 had aortic insufficiency, none symptoms. Regarding the structural
      alterations of the right cavities: 8 adults with CVID had right cavities growth
      and 5 of them, hypermobile atrial septum was reported; respect to functional
      alterations, 24 patients had tricuspid insufficiency; in 20 it was mild and only
      in 3 is was moderate. Up to 12 had pulmonary valve insufficiency, and 8 had
      pulmonary arterial hypertension (PAH); of which, in 2 it was mild and in one it
      was moderate; and 4 patients had PSAP in high limit values. CONCLUSIONS: Patients
      with CVID, despite having a high incidence of bronchiectasis, had low incidence
      of PAH, but a significant number of patients had PSAP in high cutoff level, so,
      these patients should be monitored annually, because probably they will evolve to
      PAH in the future. Also, they have a high incidence of mild valvular
      regurgitation due to mild degenerative changes with valvular sclerosis,
      therefore, they also require regular monitoring.

PMID- 25958372
TI  - [Profile of sensitization to allergens in children with atopic dermatitis
      assisting to Allergology Service of University Hospital, Nuevo Leon, Mexico].
AB  - BACKGROUND: Sensitization to allergens in atopic dermatitis patients is a risk
      factor for developing asthma and allergic rhinitis in the future,as well as an
      aggravating factor in the course of the disease. Recent studies have attributed
      the activity of the proteases of some antigens to cause a grater defect in the
      epithelial barrier and a more severe disease. OBJECTIVE: To know the
      sensitization to allergens pattern in children with atopic dermatitis attended at
      Allergology Service of University Hospital of UANL, Mexico, and to know if these
      children have higher sensitization to antigens with proteolytic activity.
      MATERIAL AND METHOD: A retrospective study was done reviewing the skin prick test
      reports done in our service to children ranging from 5 months to 16 years old,
      diagnosed with atopic dermatitis during a period of 2 years, from January 2012 to
      January 2014. The frequency of sensitization to aeroallergens and food were
      analyzed as well as the weal size (>=6mm) on the skin in response to each
      particular allergen in the case of food skin prick test. RESULTS: Reports of skin
      tests of 66 children, 30 boys and 36 girls, were included; 37 of children were
      sensitized to more than one allergen,18/66 had asthma and/or allergic rhinitis,
      40/66 60% skin prick tests were positive to high activity protease aeroallergens
      (Dermatophagoides pteronyssinus/Dermatophagoides farinae). Regarding food,
      sensitization was seen in 38 children; fruits and vegetables were the two most
      common foods. Only seven children had skin prick weal bigger than 6 mm, mainly to
      egg, fish and cow's milk. CONCLUSIONS: Children with atopic dermatitis are often
      sensitized to high protease activity aeroallergens, polysensitization is very
      common and the association with airway allergy is seen early in life.
      Sensitization to food is also common in these patients, but only a small
      percentage showed a response large enough to be associated with disease severity.

PMID- 25958373
TI  - [Orofacial clinical manifestations in adult patients with variable common
      immunodeficiency].
AB  - BACKGROUND: Common variable immunodeficiency is the primary immunodeficiency
      (CVID) frequently found in adults. Its prevalence is estimated from 1:25,000 to
      75,000 alive newborns; there are variations by ethnic groups, it is estimated
      about 50-70% in Caucasian patients. Oral cavity lesions are rarely found in adult
      patients with CVID, there are reports about lesions on pediatric patients mostly
      caused by infections. OBJECTIVE: To describe the orofacial lesions (oral,
      maxillofacial and neck area) affecting adults with CVID. MATERIAL AND METHOD: A
      transversal, prospective study was done in patients with CVID attended at
      Specialties Hospital, CMN SXXI, Mexico City. Patients where examined by the oral
      and maxillofacial surgeon and clinical findings were reported, then the
      descriptive analysis of the lesions was done. RESULTS: We evaluated 26 patients,
      16 female and 10 males, average age of 38.6 years. In 18/26 patients we found
      oral lesions on 7 different types. The most frequent was minor salivary glands
      hiperplasia (19/26),petechiae (12/26) and herpetic ulcers (7/26). In head and
      neck, we found 4 different lesions, the most common was lymphadenopathy <2cm
      (4/26). CONCLUSIONS: The immunologic alterations associated to CVID favors the
      development of lesions mainly of infectious and probably autoinmune origin that
      affects the oral cavity and head and neck area.

PMID- 25958374
TI  - [Oral anaphylaxis by ingestion of mite contaminated food in Panama City, 2011
      2014].
AB  - BACKGROUND: Oral mite anaphylaxis (OMA), or pancake syndrome, occurs in atopic
      individuals when eating starchy foods contaminated by mites, which induce
      moderate or severe, even fatal, allergic reactions. This syndrome is usually seen
      in tropical and subtropical environments,where conditions for the growth of
      domestic mites are given. Oral mite anaphylaxis has been associated with
      hypersensitivity to acetylsalicylic acid (ASA)-non-steroidal anti-inflammatory
      drugs (NSAID) and physical exercise. OBJECTIVE: To document the clinical and
      descriptive study of cases of OMA attended in City of Panama from 2011 to 2014.
      MATERIAL AND METHOD: A clinical descriptive and retrospective study was
      performed, including skin prick test to five species of domestic mites. Taxonomic
      identification of the mites was performed under microscope and its density per
      gram of food was calculated for three cases. RESULTS: Ten cases with clinical
      history compatible with OMA were studied, being the pancakes the most
      incriminated food. The onset of symptoms occurred between 25 and 60 minutes after
      ingestion of the food. All patients were atopic young adults. Four of the ten
      patients had hypersensitivity to ASA-NSAID. The patients were positive to Prick
      test mites: Blomia tropicalis, Dermatophagoides pteronyssinus and Suidasia
      pontifica. The three samples of wheat flour studied presented high densities of
      mites per gram. CONCLUSIONS: The pancakes were the most incriminated food in the
      cases of OMA in our study. Suidasia pontifica and Blomia tropicalis seem to be
      the mites species of greater relevance related with this syndrome in our country.

PMID- 25958375
TI  - [Expression of CD152 and CD137 on T regulatory cells in rhinitis and bronchial
      asthma patients].
AB  - BACKGROUND: Allergic rhinitis and bronchial asthma are inflammatory conditions
      that have increased in prevalence over the past two decades; studies of the
      inflammatory response in these diseases have determined that T regulatory cells
      (Treg) have been considered as responsible for allergens tolerance. The
      expression of CTLA-4 (CD152) in Treg is associated with the functional activity
      of this population, moreover the expression of 4-1BB (CD137) has a controversial
      function. OBJECTIVE: To determine the existence of CTLA-4 and 4-1BB in Treg cells
      in peripheral blood of patients with rhinitis and/or asthma. MATERIAL AND METHOD:
      A comparative cross-sectional study was done with three groups of patients: 20
      subjects with allergic rhinitis, 17 subjects with bronchial asthma and 17
      subjects with both disorders; 19 healthy subjects conformed the control group.
      The frequency of Treg (CD4+, FoxP3+ and CD25hight) and the expression of CD152
      and CD137 in these cells were assessed by flow cytometry in peripheral blood.
      RESULTS: We found that the group of subjects with bronchial asthma (p<0.001) and
      allergic rhinitis bronchial asthma (p<0.001) showed a significantly lower
      percentage of Treg (CD4+, CD25hight and FoxP3+) in peripheral blood compared to
      the healthy subjects controls. Only the group of subjects with bronchial asthma
      showed a significantly higher percentage of CD152+ (p<0.01) and CD137+ (p<0.01)
      Treg compared to control group. CONCLUSIONS: Subjects with bronchial asthma and
      bronchial asthma and allergic rhinitis disorders have a deficiency of CD4+,
      CD25hight and FoxP3+ Treg in peripheral blood; however, subjects with bronchial
      asthma had a higher frequency of CD152+ and CD137+ Treg cells.

PMID- 25958376
TI  - [Discriminant analysis to predict the clinical diagnosis of primary
      immunodeficiencies: a preliminary report].
AB  - BACKGROUND: The features in a clinical history from a patient with suspected
      primary immunodeficiency (PID) direct the differential diagnosis through pattern
      recognition. PIDs are a heterogeneous group of more than 250 congenital diseases
      with increased susceptibility to infection, inflammation, autoimmunity, allergy
      and malignancy. Linear discriminant analysis (LDA) is a multivariate supervised
      classification method to sort objects of study into groups by finding linear
      combinations of a number of variables. OBJECTIVE: To identify the features that
      best explain membership of pediatric PID patients to a group of defect or
      disease. MATERIAL AND METHOD: An analytic cross-sectional study was done with a
      pre-existing database with clinical and laboratory records from 168 patients with
      PID, followed at the National Institute of Pediatrics during 1991-2012, it was
      used to build linear discriminant models that would explain membership of each
      patient to the different group defects and to the most prevalent PIDs in our
      registry. After a preliminary run only 30 features were included (4 demographic,
      10 clinical, 10 laboratory, 6 germs), with which the training models were
      developed through a stepwise regression algorithm. We compared the automatic
      feature selection with a selection made by a human expert, and then assessed the
      diagnostic usefulness of the resulting models (sensitivity, specificity,
      prediction accuracy and kappa coefficient), with 95% confidence intervals.
      RESULTS: The models incorporated 6 to 14 features to explain membership of PID
      patients to the five most abundant defect groups (combined, antibody, well
      defined, dysregulation and phagocytosis), and to the four most prevalent PID
      diseases (X-linked agammaglobulinemia, chronic granulomatous disease, common
      variable immunodeficiency and ataxiatelangiectasia). In practically all cases of
      feature selection the machine outperformed the human expert. Diagnosis prediction
      using the equations created had a global accuracy of 83 to 94%, with sensitivity
      of 60 to 100%, specificity of 83 to 95% and kappa coefficient of 0.37 to 0.76.
      CONCLUSIONS: In general, the selection of features has clinical plausibility, and
      the practical advantage of utilizing only clinical attributes, infecting germs
      and routine lab results (blood cell counts and serum immunoglobulins). The
      performance of the model as a diagnostic tool was acceptable. The study's main
      limitations are a limited sample size and a lack of cross validation. This is
      only the first step in the construction of a machine learning system, with a
      wider approach that includes a larger database and different methodologies, to
      assist the clinical diagnosis of primary immunodeficiencies.

PMID- 25958377
TI  - [Updating the concept of asthma. Is asthma a syndrome?].
AB  - Several symptoms are common to different processes that affect the respiratory
      system and their precise assessment is key to a correct diagnosis. Amongst those
      symptoms, mostly dyspnoea oriented toward the possible diagnosis of asthma.
      Nevertheless, the concept of asthma has changed in recent times, as inflammation
      of the bronchial tree is valued as the pathogenic base of the process, although
      it can not be ignored that the bronchial hyperresponsiveness is still the basis
      of dyspnoea crisis. In the last years, several variants have been established,
      being defined as phenotypes and endotypes that can identify diverse asthmatic or
      pseudo-asthmatic processes, and there for it is questioned if asthma is not the
      only process, but a syndrome. In any case, it cannot be ignored that dyspnoea
      episodes can be based on bronchial hyperresponsiveness of genetic origin or due
      to inflammation because of unfavourable environmental conditions, as well as
      physical exercise or the ingestion of aspirin, processes in which other
      mechanisms are involved. 

PMID- 25958378
TI  - [Allergic hypersensitivity to antiretroviral drugs: etravirine, raltegravir and
      darunavir].
AB  - All antiretroviral drugs can have both short-term and long-term adverse events.
      The risk of specific side effects varies from drug to drug, from drug class to
      drug class, and from patient to patient. A better understanding of the adverse
      effects of antiretroviral agents is of interest not only for HIV specialists, but
      also for other physicians who care allergy reactions in HIV-positive patients.
      Each antiretroviral medication is associated with its own specific adverse
      effects or may cause problems only in particular circumstances. In this article
      some adverse allergic effects of HAART therapy in the treatment of HIV from a
      patient are reviewed. Our aim is to gain a working knowledge of these adverse
      effects, promoting the early recognition and reversal of potentially serious
      adverse effects, and reducing the potential for adverse drug interactions. 

PMID- 25958379
TI  - [DRESS syndrome or reaction to drugs with eosinophilia and systemic symptoms
      associated to anti-tuberculosis drugs].
AB  - Tuberculosis has increased all over the world. This paper reports the case of a
      male patient with tuberculous meningitis, spinal tuberculosis (Pott's disease)
      and severe adverse reactions to antituberculosis drugs. He had skin rash,
      hepatitis, eosinophilia and fever; all these signs make the diagnosis of DRESS
      syndrome. This syndrome is caused by a severe hypersensitivity reaction to
      different drugs. It is usually caused by anticonvulsants, sulfonamides and some
      antiviral drugs, among other drugs. Anti-tuberculosis drugs can also cause this
      potentially fatal syndrome. The importance of surveillance for early detection
      and treatment of adverse drug reactions is emphasized. 

PMID- 25958380
TI  - Suicide in India.
AB  - SOURCES OF DATA: The current report reviews the data from the series Accidental
      Death and Suicide in India published by India's National Crime Records Bureau
      (NCRB) reporting official suicide rates based on police reports over the period
      of 10 years from 2004 to 2013. A reference to wider literature is made to present
      a comprehensive picture. AREAS OF AGREEMENT: Suicide in India is more prevalent
      in young, is likely to involve hanging and ingestion of pesticides and is related
      to social and economic causes. Reducing alcohol consumption, unemployment,
      poverty, social inequities, domestic violence and improving social justice are
      essential to reduce suicide in India. AREAS OF CONTROVERSY: NCRB data might
      underreport suicide. Discrepancy in farmers' suicide rate between reports
      suggests that this might be overrepresented in NCRB data. GROWING POINTS: An
      integrated suicide prevention programme with a multidimensional approach is
      needed. Mental health care bill and the recent launch of first national mental
      health policy are welcome measures. Decriminalization of suicide is likely to
      positively influence mental health practice and policy in India. AREA TIMELY FOR
      DEVELOPING RESEARCH: Nationally representative studies investigating fatal and
      non-fatal suicidal behaviours, evaluation of models of service delivery for the
      vulnerable population, investigating suicide following different treatment
      services and effects of decriminalization of suicide on suicide rates should be
      the focus of future research.

PMID- 25958381
TI  - Long-term outcomes in Ornithine Transcarbamylase deficiency: a series of 90
      patients.
AB  - BACKGROUND: The principal aim of this study was to investigate the long-term
      outcomes of a large cohort of patients with ornithine transcarbamylase deficiency
      (OTCD) who were followed up at a single medical center. METHODS: We analyzed
      clinical, biochemical and genetic parameters of 90 patients (84 families, 48
      males and 42 females) with OTCD between 1971 and 2011. RESULTS: Twenty-seven
      patients (22 boys, 5 girls) had a neonatal presentation; 52 patients had an
      "intermediate" late-onset form of the disease (21 boys, 31 girls) that was
      revealed between 1 month and 16 years; and 11 patients (5 boys, 6 girls)
      presented in adulthood (16 to 55 years). Patients with a neonatal presentation
      had increased mortality (90% versus 13% in late-onset forms) and peak plasma
      ammonium (mean value: 960 MUmol/L versus 500 MUmol/L) and glutamine (mean value:
      4110 MUmol/L versus 1000 MUmol/L) levels at diagnosis. All of the neonatal forms
      displayed a greater number of acute decompensations (mean value: 6.2/patient
      versus 2.5 and 1.4 in infants and adults, respectively). In the adult group, some
      patients even recently died at the time of presentation during their first
      episode of coma. Molecular analyses identified a deleterious mutation in 59/68
      patients investigated. Single base substitutions were detected more frequently
      than deletions (69% and 12%, respectively), with a recurrent mutation identified
      in the late-onset groups (pArg40 His; 13% in infants, 57% in adults); inherited
      mutations represented half of the cases. The neurological score did not differ
      significantly between the patients who were alive in the neonatal or late-onset
      groups and did not correlate with the peak ammonia and plasma glutamine
      concentrations at diagnosis. However, in late-onset forms of the disease, ammonia
      levels adjusted according to the glutamine/citrulline ratio at diagnosis were
      borderline predictors of low IQ (p = 0.12 by logistic regression; area under the
      receiver operating characteristic curve of 76%, p <0.05). CONCLUSIONS: OTCD
      remains a severe disease, even in adult-onset patients for whom the prevention of
      metabolic decompensations is crucial. The combination of biochemical markers
      warrants further investigations to provide additional prognostic information
      regarding the neurological outcomes of patients with OTCD.

PMID- 25958383
TI  - Family planning use among women living with HIV: knowing HIV positive status
      helps - results from a national survey.
AB  - BACKGROUND: Women living with HIV continues to encounter unintended pregnancies
      with a concomitant risk of mother-to-child transmission of HIV infection.
      Preventing unintended pregnancy among HIV-infected women is one of the strategies
      in the prevention of new HIV infections among children. The aim of this analysis
      was to assess the practice of family planning (FP) among HIV-infected women and
      the influence of women's awareness of HIV positive status in the practice of FP.
      METHODS: The analysis was made in the Malawi Demographic and Health Survey (DHS)
      data among 489 non-pregnant, sexually active, fecund women living with HIV.
      Multiple logistic regression analysis was performed using SPSS software to
      identify the factors associated with FP use. Adjusted odds ratios (AOR) with 95 %
      confidence intervals were computed to assess the association of different factors
      with the practice of family planning. RESULT: Of the 489 confirmed HIV positive
      women, 184 (37.6 %) reported that they knew that they were HIV positive. The
      number of women who reported that they were currently using FP method(s) were 251
      (51.2 %). The number of women who reported unmet need for FP method(s) were 107
      (21.9 %). In the multiple logistic regression analysis, women's knowledge of HIV
      positive status [AOR: 2.32(1.54, 3.50)], secondary and above education [AOR:
      2.36(1.16, 4.78)], presence of 3-4 alive children [AOR: 2.60(1.08, 6.28)] and
      more than 4 alive children [AOR: 3.03(1.18, 7.82)] were significantly associated
      with current use of FP. CONCLUSION: Women's knowledge of their HIV-positive
      status was found to be a significant predictor of their FP practice. Health
      managers and clinicians need to improve HIV counselling and testing coverage
      among women of child-bearing age and address the FP needs of HIV-infected women.

PMID- 25958382
TI  - Russia-specific relative risks and their effects on the estimated alcohol
      attributable burden of disease.
AB  - BACKGROUND: Alcohol consumption is a major risk factor for the burden of disease
      globally. This burden is estimated using Relative Risk (RR) functions for alcohol
      from meta-analyses that use data from all countries; however, for Russia and
      surrounding countries, country-specific risk data may need to be used. The
      objective of this paper is to compare the estimated burden of alcohol consumption
      calculated using Russia-specific alcohol RRs with the estimated burden of alcohol
      consumption calculated using alcohol RRs from meta-analyses. METHODS: Data for
      2012 on drinking indicators were calculated based on the Global Information
      System on Alcohol and Health. Data for 2012 on mortality, Years of Life Lost,
      Years Lived with Disability, and Disability-Adjusted Life Years (DALYs) lost by
      cause were obtained by country from the World Health Organization. Alcohol
      Population-Attributable Fractions (PAFs) were calculated based on a risk
      modelling methodology from Russia. These PAFs were compared to PAFs calculated
      using methods applied for all other countries. The 95% Uncertainty Intervals
      (UIs) for the alcohol PAFs were calculated using a Monte Carlo-like method.
      RESULTS: Using Russia-specific alcohol RR functions, in Russia in 2012 alcohol
      caused an estimated 231,900 deaths (95% UI: 185,600 to 278,200) (70,800 deaths
      among women and 161,100 deaths among men) and 13,295,000 DALYs lost (95% UI:
      11,242,000 to 15,348,000) (3,670,000 DALYs lost among women and 9,625,000 DALYs
      lost among men) among people 0 to 64 years of age. This compares to an estimated
      165,600 deaths (95% UI: 97,200 to 228,100) (29,700 deaths among women and 135,900
      deaths among men) and 10,623,000 DALYs lost (95% UI: 7,265,000 to 13,754,000)
      (1,783,000 DALYs lost among women and 8,840,000 DALYs lost among men) among
      people 0 to 64 years of age caused by alcohol when non-Russia-specific alcohol
      RRs were used. CONCLUSIONS: Results indicate that if the Russia-specific RRs are
      used when estimating the health burden attributable to alcohol consumption in
      Russia, then the total estimated burden will be more than if RRs from meta
      analyses are used. Furthermore, additional research is needed to understand which
      aspects of the Russian style of drinking cause the most harm.

PMID- 25958384
TI  - NBPF1, a tumor suppressor candidate in neuroblastoma, exerts growth inhibitory
      effects by inducing a G1 cell cycle arrest.
AB  - BACKGROUND: NBPF1 (Neuroblastoma Breakpoint Family, member 1) was originally
      identified in a neuroblastoma patient on the basis of its disruption by a
      chromosomal translocation t(1;17)(p36.2;q11.2). Considering this genetic defect
      and the frequent genomic alterations of the NBPF1 locus in several cancer types,
      we hypothesized that NBPF1 is a tumor suppressor. Decreased expression of NBPF1
      in neuroblastoma cell lines with loss of 1p36 heterozygosity and the marked
      decrease of anchorage-independent clonal growth of DLD1 colorectal carcinoma
      cells with induced NBPF1 expression further suggest that NBPF1 functions as tumor
      suppressor. However, little is known about the mechanisms involved. METHODS:
      Expression of NBPF was analyzed in human skin and human cervix by
      immunohistochemistry. The effects of NBPF1 on the cell cycle were evaluated by
      flow cytometry. We investigated by real-time quantitative RT-PCR the expression
      profile of a panel of genes important in cell cycle regulation. Protein levels of
      CDKN1A-encoded p21(CIP1/WAF1) were determined by western blotting and the
      importance of p53 was shown by immunofluorescence and by a loss-of-function
      approach. LC-MS/MS analysis was used to investigate the proteome of DLD1 colon
      cancer cells with induced NBPF1 expression. Possible biological interactions
      between the differentially regulated proteins were investigated with the
      Ingenuity Pathway Analysis tool. RESULTS: We show that NBPF is expressed in the
      non-proliferative suprabasal layers of squamous stratified epithelia of human
      skin and cervix. Forced expression of NBPF1 in HEK293T cells resulted in a G1
      cell cycle arrest that was accompanied by upregulation of the cyclin-dependent
      kinase inhibitor p21(CIP1/WAF1) in a p53-dependent manner. Additionally, forced
      expression of NBPF1 in two p53-mutant neuroblastoma cell lines also resulted in a
      G1 cell cycle arrest and CDKN1A upregulation. However, CDKN1A upregulation by
      NBPF1 was not observed in the DLD1 cells, which demonstrates that NBPF1 exerts
      cell-specific effects. In addition, proteome analysis of NBPF1-overexpressing
      DLD1 cells identified 32 differentially expressed proteins, of which several are
      implicated in carcinogenesis. CONCLUSIONS: We demonstrated that NBPF1 exerts
      different tumor suppressive effects, depending on the cell line analyzed, and
      provide new clues into the molecular mechanism of the enigmatic NBPF proteins.

PMID- 25958385
TI  - Extensive characterization of Campylobacter jejuni chicken isolates to uncover
      genes involved in the ability to compete for gut colonization.
AB  - BACKGROUND: Campylobacter jejuni is responsible for human foodborne enteritis.
      This bacterium is a remarkable colonizer of the chicken gut, with some strains
      outcompeting others for colonization. To better understand this phenomenon, the
      objective of this study was to extensively characterize the phenotypic
      performance of C. jejuni chicken strains and associate their gut colonizing
      ability with specific genes. RESULTS: C. jejuni isolates (n = 45) previously
      analyzed for the presence of chicken colonization associated genes were further
      characterized for phenotypic properties influencing colonization:
      autoagglutination and chemotaxis as well as adhesion to and invasion of primary
      chicken caecal cells. This allowed strains to be ranked according to their in
      vitro performance. After their in vitro capacity to outcompete was demonstrated
      in vivo, strains were then typed by comparative genomic fingerprinting (CGF). In
      vitro phenotypical properties displayed a linear variability among the tested
      strains. Strains possessing higher scores for phenotypical properties were able
      to outcompete others during chicken colonization trials. When the gene content of
      strains was compared, some were associated with different phenotypical scores and
      thus with different outcompeting capacities. Use of CGF profiles showed an
      extensive genetic variability among the studied strains and suggested that the
      outcompeting capacity is not predictable by CGF profile. CONCLUSION: This study
      revealed a wide array of phenotypes present in C. jejuni strains, even though
      they were all recovered from chicken caecum. Each strain was classified according
      to its in vitro competitive potential and its capacity to compete for chicken gut
      colonization was associated with specific genes. This study also exposed the
      disparity existing between genetic typing and phenotypical behavior of C. jejuni
      strains.

PMID- 25958387
TI  - Wahjuhono et al [J Infect Dis 2014; 210(suppl 1): S347-52].

PMID- 25958386
TI  - Acute spontaneous subdural hematoma caused by skull metastasis of hepatocellular
      carcinoma: case report.
AB  - BACKGROUND: Skull and intracranial metastases from hepatocellular carcinoma (HCC)
      have seldom been reported. A skull metastasis of HCC with a tumor bleeding
      resulting in spontaneous subdural hematoma (SDH) is extremely unusual. We report
      the first case of acute spontaneous SDH in a 69-year-old woman who presented with
      acute onset of headache, because of tumor bleeding caused by skull metastasis of
      HCC. CASE PRESENTATION: A 69-year-old woman was referred to our hospital because
      of progressive headache, nausea, and vomiting for 3 days. Brain computed
      tomography (CT) performed in the emergency department (ED) revealed a left
      temporal SDH with a slight mass effect and a small left temporal bone erosion.
      Tri-phasic abdominal CT demonstrated a large right lobe liver tumor compatible
      with HCC. She experienced progressive deterioration of consciousness in the
      intensive care unit. Follow-up CT showed an enlargement of the SDH. An emergency
      craniotomy for hematoma evacuation and removal of skull tumor was performed. She
      regained consciousness and had no neurological deficits during the postoperative
      course. Pathological examination of the skull specimen indicated metastasis of a
      HCC. CONCLUSION: Patients with acute SDH without a history of head injury are
      rarely encountered in the ED. Metastatic carcinoma with bleeding should be
      included as a differential diagnosis for acute spontaneous SDH. Before an
      operation for SDH, the possibility of metastatic lesion of the skull should be
      considered in the surgical planning and the origin of malignancy should be
      sought.

PMID- 25958388
TI  - Radio-adaptive response of base excision repair genes and proteins in human
      peripheral blood mononuclear cells exposed to gamma radiation.
AB  - Radio-adaptive response is a mechanism whereby a low-dose exposure (priming dose)
      induces resistance to a higher dose (challenging dose) thus significantly
      reducing its detrimental effects. Radiation-induced DNA damage gets repaired
      through various DNA repair pathways in human cells depending upon the type of
      lesion. The base excision repair (BER) pathway repairs radiation-induced base
      damage, abasic sites and single-strand breaks in cellular DNA. In the present
      study, an attempt has been made to investigate the involvement of BER genes and
      proteins in the radio-adaptive response in human resting peripheral blood
      mononuclear cells (PBMC). Venous blood samples were collected from 20 randomly
      selected healthy male individuals with written informed consent. PBMC were
      isolated and irradiated at a priming dose of 0.1 Gy followed 4h later with a
      challenging dose of 2.0 Gy (primed cells). Quantitation of DNA damage was done
      using the alkaline comet assay immediately and expression profile of BER genes
      and proteins were studied 30 min after the challenging dose using real-time
      quantitative polymerase chain reaction and western blot, respectively. The
      overall result showed significant (P <= 0.05) reduction of DNA damage in terms of
      percentage of DNA in tail (%T) with a priming dose of 0.1 Gy followed by a
      challenging dose of 2.0 Gy after 4 h. Twelve individuals showed significant (P <=
      0.05) reduction in %T whereas eight individuals showed marginal reduction in DNA
      damage that was not statistically significant. However, at the transcriptional
      level, BER genes such as APE1, FEN1 and LIGASE1 showed significant (P <= 0.05) up
      regulation in both groups. Significant (P <= 0.05) up-regulation was also
      observed at the protein level for OGG1, APE1, MBD4, FEN1 and LIGASE1 in primed
      cells. Up-regulation of some BER genes and proteins such as APE1, FEN1 and
      LIGASE1 in primed cells of resting PBMC is suggestive of active involvement of
      the BER pathway in radio-adaptive response.

PMID- 25958389
TI  - Impact of exposure to wood dust on genotoxicity and cytotoxicity in exfoliated
      buccal and nasal cells.
AB  - Wood dust was classified by the IARC as a human carcinogen which causes sinonasal
      tumours. However, the exposure in different industries varies strongly and the
      risks of workers depend on the specific situation which can be assessed by the
      use of biomonitoring methods. The aim of this study was to investigate the
      workers who are exposed to low dust levels (below the permitted concentrations)
      with cytogenetic and biochemical methods. Micronuclei (MNi) which are indicative
      for genomic damage, nuclear buds which reflect gene amplification, binucleated
      cells which are caused by mitotic disturbances and acute cytotoxicity parameters
      (pyknosis, karyorrhexis, condensed chromatin, karyolysis) were monitored in
      buccal and nasal cells of workers of a veneer factory (n = 51) who are exposed to
      volatile wood-derived compounds, in carpenters of a furniture factory which use
      no synthetic chemicals (n=38) and in a control group (n = 65). Additionally,
      markers were measured in blood plasma which reflect inflammations (C-reactive
      protein, CRP) and the redox status, namely malondialdehyde (MDA) and oxidised low
      density proteins (oxLDL). No induction of micronucleated cells was observed in
      both epithelia in the two exposure groups while all other nuclear anomalies
      except pyknosis were increased; also one health-related biochemical marker (MDA)
      was significantly elevated in the workers. Taken together, the results of our
      study show that exposure to low levels of wood dust does not cause formation of
      MNi indicating that the cancer risks of the workers are not increased as a
      consequence of genetic damage while positive results were obtained in earlier
      studies with workers who are exposed to high dust levels. However, our findings
      indicate that wood dust causes cytotoxic effects which may lead to inflammations.

PMID- 25958390
TI  - Functional analysis of the new barley gene HvKu80 indicates that it plays a key
      role in double-strand DNA break repair and telomere length regulation.
AB  - Genotoxic stress causes a reduced stability of the plant genome and has a
      detrimental effect on plant growth and productivity. Double-strand breaks (DSBs)
      are the most harmful of all DNA lesions because they cause the loss of genetic
      information on both strands of the DNA helix. In the presented study the coding
      and genomic sequences of the HvKu80 gene were determined. A mutational analysis
      of two fragments of HvKu80 using TILLING (Targeting Induced Local Lesions IN
      Genomes) allowed 12 mutations to be detected, which resulted in identification of
      11 alleles. Multidirectional analyses demonstrated that the HvKu80 gene is
      involved in the elimination of DSBs in Hordeum vulgare. The barley mutants
      carrying the identified ku80.c and ku80.j alleles accumulated bleomycin-induced
      DSBs to a much greater extent than the parent cultivar 'Sebastian'. The altered
      reaction of the mutants to DSB-inducing agent and the kinetics of DNA repair in
      these genotypes are associated with a lower expression level of the mutated gene.
      The study also demonstrated the significant role of the HvKu80 gene in the
      regulation of telomere length in barley. 

PMID- 25958391
TI  - SCUDO: a tool for signature-based clustering of expression profiles.
AB  - SCUDO (Signature-based ClUstering for DiagnOstic purposes) is an online tool for
      the analysis of gene expression profiles for diagnostic and classification
      purposes. The tool is based on a new method for the clustering of profiles based
      on a subject-specific, as opposed to disease-specific, signature. Our approach
      relies on construction of a reference map of transcriptional signatures, from
      both healthy and affected subjects, derived from their respective mRNA or miRNA
      profiles. A diagnosis for a new individual can then be performed by determining
      the position of the individual's transcriptional signature on the map. The
      diagnostic power of our method has been convincingly demonstrated in an open
      scientific competition (SBV Improver Diagnostic Signature Challenge), scoring
      second place overall and first place in one of the sub-challenges. 

PMID- 25958392
TI  - PhyloGene server for identification and visualization of co-evolving proteins
      using normalized phylogenetic profiles.
AB  - Proteins that function in the same pathways, protein complexes or the same
      environmental conditions can show similar patterns of sequence conservation
      across phylogenetic clades. In species that no longer require a specific protein
      complex or pathway, these proteins, as a group, tend to be lost or diverge.
      Analysis of the similarity in patterns of sequence conservation across a large
      set of eukaryotes can predict functional associations between different proteins,
      identify new pathway members and reveal the function of previously
      uncharacterized proteins. We used normalized phylogenetic profiling to predict
      protein function and identify new pathway members and disease genes. The
      phylogenetic profiles of tens of thousands conserved proteins in the human,
      mouse, Caenorhabditis elegans and Drosophila genomes can be queried on our new
      web server, PhyloGene. PhyloGene provides intuitive and user-friendly platform to
      query the patterns of conservation across 86 animal, fungal, plant and protist
      genomes. A protein query can be submitted either by selecting the name from whole
      genome protein sets of the intensively studied species or by entering a protein
      sequence. The graphic output shows the profile of sequence conservation for the
      query and the most similar phylogenetic profiles for the proteins in the genome
      of choice. The user can also download this output in numerical form. 

PMID- 25958393
TI  - NaviCell Web Service for network-based data visualization.
AB  - Data visualization is an essential element of biological research, required for
      obtaining insights and formulating new hypotheses on mechanisms of health and
      disease. NaviCell Web Service is a tool for network-based visualization of
      'omics' data which implements several data visual representation methods and
      utilities for combining them together. NaviCell Web Service uses Google Maps and
      semantic zooming to browse large biological network maps, represented in various
      formats, together with different types of the molecular data mapped on top of
      them. For achieving this, the tool provides standard heatmaps, barplots and
      glyphs as well as the novel map staining technique for grasping large-scale
      trends in numerical values (such as whole transcriptome) projected onto a pathway
      map. The web service provides a server mode, which allows automating
      visualization tasks and retrieving data from maps via RESTful (standard HTTP)
      calls. Bindings to different programming languages are provided (Python and R).
      We illustrate the purpose of the tool with several case studies using pathway
      maps created by different research groups, in which data visualization provides
      new insights into molecular mechanisms involved in systemic diseases such as
      cancer and neurodegenerative diseases. 

PMID- 25958395
TI  - Pse-in-One: a web server for generating various modes of pseudo components of
      DNA, RNA, and protein sequences.
AB  - With the avalanche of biological sequences generated in the post-genomic age, one
      of the most challenging problems in computational biology is how to effectively
      formulate the sequence of a biological sample (such as DNA, RNA or protein) with
      a discrete model or a vector that can effectively reflect its sequence pattern
      information or capture its key features concerned. Although several web servers
      and stand-alone tools were developed to address this problem, all these tools,
      however, can only handle one type of samples. Furthermore, the number of their
      built-in properties is limited, and hence it is often difficult for users to
      formulate the biological sequences according to their desired features or
      properties. In this article, with a much larger number of built-in properties, we
      are to propose a much more flexible web server called Pse-in-One
      (http://bioinformatics.hitsz.edu.cn/Pse-in-One/), which can, through its 28
      different modes, generate nearly all the possible feature vectors for DNA, RNA
      and protein sequences. Particularly, it can also generate those feature vectors
      with the properties defined by users themselves. These feature vectors can be
      easily combined with machine-learning algorithms to develop computational
      predictors and analysis methods for various tasks in bioinformatics and system
      biology. It is anticipated that the Pse-in-One web server will become a very
      useful tool in computational proteomics, genomics, as well as biological sequence
      analysis. Moreover, to maximize users' convenience, its stand-alone version can
      also be downloaded from http://bioinformatics.hitsz.edu.cn/Pse-in-One/download/,
      and directly run on Windows, Linux, Unix and Mac OS. 

PMID- 25958394
TI  - Intercalation processes of copper complexes in DNA.
AB  - The family of anticancer complexes that include the transition metal copper known
      as Casiopeinas(r) shows promising results. Two of these complexes are currently
      in clinical trials. The interaction of these compounds with DNA has been observed
      experimentally and several hypotheses regarding the mechanism of action have been
      developed, and these include the generation of reactive oxygen species, phosphate
      hydrolysis and/or base-pair intercalation. To advance in the understanding on how
      these ligands interact with DNA, we present a molecular dynamics study of 21
      Casiopeinas with a DNA dodecamer using 10 MUs of simulation time for each
      compound. All the complexes were manually inserted into the minor groove as the
      starting point of the simulations. The binding energy of each complex and the
      observed representative type of interaction between the ligand and the DNA is
      reported. With this extended sampling time, we found that four of the compounds
      spontaneously flipped open a base pair and moved inside the resulting cavity and
      four compounds formed stacking interactions with the terminal base pairs. The
      complexes that formed the intercalation pocket led to more stable interactions. 

PMID- 25958396
TI  - The identity of the discriminator base has an impact on CCA addition.
AB  - CCA-adding enzymes synthesize and maintain the C-C-A sequence at the tRNA 3'-end,
      generating the attachment site for amino acids. While tRNAs are the most
      prominent substrates for this polymerase, CCA additions on non-tRNA transcripts
      are described as well. To identify general features for substrate requirement, a
      pool of randomized transcripts was incubated with the human CCA-adding enzyme.
      Most of the RNAs accepted for CCA addition carry an acceptor stem-like terminal
      structure, consistent with tRNA as the main substrate group for this enzyme.
      While these RNAs show no sequence conservation, the position upstream of the CCA
      end was in most cases represented by an adenosine residue. In tRNA, this position
      is described as discriminator base, an important identity element for correct
      aminoacylation. Mutational analysis of the impact of the discriminator identity
      on CCA addition revealed that purine bases (with a preference for adenosine) are
      strongly favoured over pyrimidines. Furthermore, depending on the tRNA context, a
      cytosine discriminator can cause a dramatic number of misincorporations during
      CCA addition. The data correlate with a high frequency of adenosine residues at
      the discriminator position observed in vivo. Originally identified as a prominent
      identity element for aminoacylation, this position represents a likewise
      important element for efficient and accurate CCA addition. 

PMID- 25958400
TI  - Gram-negative bacteraemia in haemodialysis.
AB  - BACKGROUND: Patients on renal replacement therapy experience higher rates of
      morbidity and mortality, infection being the second commonest cause of death. In
      our haemodialysis population, we identify the pathogens, sensitivity patterns,
      sources of infection and outcomes of Gram-negative bacteraemia. METHODS: Data
      from the NHS Greater Glasgow & Clyde and NHS Forth Valley haemodialysis
      population were collected July 2011 to April 2014 through an interrogation of the
      renal unit electronic patient record, and confirmed by an independent search of
      the Microbiology database. RESULTS: Over 544 377 haemodialysis days, 84 patients
      experienced 95 Gram-negative bacteraemia events, a rate of 0.175 events per 1000
      haemodialysis days, which varied with dialysis modality: non-tunnelled central
      venous catheters 4.77, arteriovenous grafts 0.24, tunnelled central venous
      catheters 0.21, and arteriovenous fistulae 0.11 per 1000 haemodialysis days. The
      commonest sources of bacteraemia were central venous catheters (CVCs) (16.8%, n =
      16), infected ulcers (14.7%, n = 14), urinary (10.5%, n = 10), biliary (9.5%, n =
      9) and intra-abdominal (9.5%, n = 9).The principal organisms were Escherichia
      coli (49.5%, n = 47), Enterobacter spp. (13.1%, n = 13), Klebsiella spp. (11.1%,
      n = 11), Proteus mirabilis (6.1%, n = 6) and Pseudomonas aeruginosa (5.1%, n =
      5). Of the Enterobacteriaceae (n = 84), 88% were sensitive to gentamicin, 81% to
      ciprofloxacin, 91% to piperacillin-tazobactam and 100% were sensitive to
      meropenem.Three-month case mortality was 25.3% (n = 24). Ten patients (11.9%) had
      more than one Gram-negative bacteraemia; of these, nine patients (90.0%) were the
      same causative organism, predominantly E. coli. CONCLUSIONS: CVCs and diabetic
      foot ulcers remain significant risk factors for Gram-negative bacteraemia,
      highlighting the importance of vascular access planning. Despite good levels of
      antibiotic sensitivity, the early mortality following Gram-negative bacteraemia
      remains high, supporting aggressive treatment of such pathogens.

PMID- 25958397
TI  - Duplex stem-loop-containing quadruplex motifs in the human genome: a combined
      genomic and structural study.
AB  - Duplex stem-loops and four-stranded G-quadruplexes have been implicated in
      (patho)biological processes. Overlap of stem-loop- and quadruplex-forming
      sequences could give rise to quadruplex-duplex hybrids (QDH), which combine
      features of both structural forms and could exhibit unique properties. Here, we
      present a combined genomic and structural study of stem-loop-containing
      quadruplex sequences (SLQS) in the human genome. Based on a maximum loop length
      of 20 nt, our survey identified 80 307 SLQS, embedded within 60 172 unique
      clusters. Our analysis suggested that these should cover close to half of total
      SLQS in the entire genome. Among these, 48 508 SLQS were strand-specifically
      located in genic/promoter regions, with the majority of genes displaying a low
      number of SLQS. Notably, genes containing abundant SLQS clusters were strongly
      associated with brain tissues. Enrichment analysis of SLQS-positive genes and
      mapping of SLQS onto transcriptional/mutagenesis hotspots and cancer-associated
      genes, provided a statistical framework supporting the biological involvements of
      SLQS. In vitro formation of diverse QDH by selective SLQS hits were successfully
      verified by nuclear magnetic resonance spectroscopy. Folding topologies of two
      SLQS were elucidated in detail. We also demonstrated that sequence changes at
      mutation/single-nucleotide polymorphism loci could affect the structural
      conformations adopted by SLQS. Thus, our predicted SLQS offer novel insights into
      the potential involvement of QDH in diverse (patho)biological processes and could
      represent novel regulatory signals. 

PMID- 25958399
TI  - Identification of human telomerase assembly inhibitors enabled by a novel method
      to produce hTERT.
AB  - Telomerase is the enzyme that maintains the length of telomeres. It is minimally
      constituted of two components: a core reverse transcriptase protein (hTERT) and
      an RNA (hTR). Despite its significance as an almost universal cancer target, the
      understanding of the structure of telomerase and the optimization of specific
      inhibitors have been hampered by the limited amount of enzyme available. Here, we
      present a breakthrough method to produce unprecedented amounts of recombinant
      hTERT and to reconstitute human telomerase with purified components. This system
      provides a decisive tool to identify regulators of the assembly of this
      ribonucleoprotein complex. It also enables the large-scale screening of small
      molecules capable to interfere with telomerase assembly. Indeed, it has allowed
      us to identify a compound that inhibits telomerase activity when added prior to
      the assembly of the enzyme, while it has no effect on an already assembled
      telomerase. Therefore, the novel system presented here may accelerate the
      understanding of human telomerase assembly and facilitate the discovery of potent
      and mechanistically unique inhibitors.

PMID- 25958398
TI  - Design and bioinformatics analysis of genome-wide CLIP experiments.
AB  - The past decades have witnessed a surge of discoveries revealing RNA regulation
      as a central player in cellular processes. RNAs are regulated by RNA-binding
      proteins (RBPs) at all post-transcriptional stages, including splicing,
      transportation, stabilization and translation. Defects in the functions of these
      RBPs underlie a broad spectrum of human pathologies. Systematic identification of
      RBP functional targets is among the key biomedical research questions and
      provides a new direction for drug discovery. The advent of cross-linking
      immunoprecipitation coupled with high-throughput sequencing (genome-wide CLIP)
      technology has recently enabled the investigation of genome-wide RBP-RNA binding
      at single base-pair resolution. This technology has evolved through the
      development of three distinct versions: HITS-CLIP, PAR-CLIP and iCLIP. Meanwhile,
      numerous bioinformatics pipelines for handling the genome-wide CLIP data have
      also been developed. In this review, we discuss the genome-wide CLIP technology
      and focus on bioinformatics analysis. Specifically, we compare the strengths and
      weaknesses, as well as the scopes, of various bioinformatics tools. To assist
      readers in choosing optimal procedures for their analysis, we also review
      experimental design and procedures that affect bioinformatics analyses. 

PMID- 25958401
TI  - Asymmetry in CT Scan Measures of Thigh Muscle 2 Months After Hip Fracture: The
      Baltimore Hip Studies.
AB  - BACKGROUND: Hip fracture is an important problem for older adults with
      significant functional consequences. After hip fracture, reduced muscle loading
      can result in muscle atrophy. METHODS: We compared thigh muscle characteristics
      in the fractured leg with those in the nonfractured leg in participants from the
      Baltimore Hip Studies 7th cohort using computed tomography (CT) scan imaging.
      RESULTS: At 2 months postfracture, a single 10-mm axial CT scan was obtained at
      the midthigh level in 47 participants (26 men and 21 women) with a mean age of
      80.4 years (range 65-96), and thigh muscle cross-sectional area (CSA), CSA of
      intermuscular adipose tissue (IMAT), as well as mean radiological attenuation
      were measured. Total thigh muscle CSA was less on the side of the fracture by 9.2
      cm(2) (95% CI: 5.9, 12.4 cm(2)), whereas the CSA of IMAT was greater by 2.8 cm(2)
      (95% CI: 1.9, 3.8 cm(2)) on the fractured side. Mean muscle attenuation was lower
      on the side of the fracture by 3.61 HU (95% CI: 2.99, 4.24 HU). CONCLUSIONS: The
      observed asymmetry is consistent with the effect of disuse and inflammation in
      the affected limb along with training effects in the unaffected limb due to the
      favoring of this leg with ambulation during the postfracture period.

PMID- 25958410
TI  - Erratum.

PMID- 25958409
TI  - The evolving role of the endocannabinoid system in gynaecological cancer.
AB  - BACKGROUND: The 'endocannabinoid system' (ECS), comprising endogenous ligands
      (endocannabinoids) and their regulating enzymes, together with the cannabinoid
      receptors, has attracted a great deal of attention because it affects not only
      all facets of human reproduction, from gametogenesis through to parturition and
      beyond, but also targets key mechanisms affecting some hallmarks of cancer.
      Recent evidence showing that cannabinoid receptors play a very important role in
      the development of malignancies outside of the reproductive organs suggests a
      similar role for the ECS in the establishment or continued development of
      gynaecological malignancy. METHODS: Primary papers and review articles, and
      primary sources within these papers, up to December 2014, on the evolving role of
      the ECS in cancer, with a special focus on gynaecological cancers, were obtained
      by Medline and PubMed searches using the search terms: 'cancer', 'cannabinoid',
      'endocannabinoid', 'gynaecology' and 'malignancy'. Non-English manuscripts were
      excluded. RESULTS: More than 2100 sources were obtained from which only 112 were
      specifically important to the topic. Analysis of those articles supports a role
      of the ECS in gynaecological cancers but leaves many gaps in our knowledge that
      need to be filled. How some of the relevant receptors are activated and cause
      changes in cell phenotypes that progress to malignancy remains undiscovered and
      an area for future research. Increasing evidence suggests that malignant
      transformation within the female genital tract could be accompanied by
      deregulation of components of the ECS, acting through rather complex cannabinoid
      receptor-dependent and receptor-independent mechanisms. CONCLUSIONS: The paucity
      of studies in this area suggests that research using animal models is needed to
      evaluate endocannabinoid signalling in cancer networks. Future randomized
      clinical studies should reveal whether endocannabinoids or their derivatives
      prove to be useful therapeutic targets for gynaecological and other cancers.

PMID- 25958411
TI  - Energy dependence of the complexity of DNA damage induced by carbon ions.
AB  - To assess the complexity of DNA damage induced by carbon ions as a function of
      their energy and LET, 2-Gy irradiations by 100 keV u(-1)-400 MeV u(-1) carbon
      ions were investigated using the PARTRAC code. The total number of fragments and
      the yield of fragments of <30 bp were calculated. The authors found a
      particularly important contribution of DNA fragmentation in the range of <1 kbp
      for specific energies of <6 MeV u(-1). They also considered the effect of
      different specific energies with the same LET, i.e. before and after the Bragg
      peak. As a first step towards a full characterisation of secondary particle
      production from carbon ions interacting with tissue, a comparison between DNA
      damage induction by primary carbon ions and alpha particles resulting from carbon
      break-up is presented, for specific energies of >1 MeV u(-1). 

PMID- 25958412
TI  - Neutron flux characterisation of the Pavia TRIGA Mark II research reactor for
      radiobiological and microdosimetric applications.
AB  - Nowadays the Pavia TRIGA reactor is available for national and international
      collaboration in various research fields. The TRIGA Mark II nuclear research
      reactor of the Pavia University offers different in- and out-core neutron
      irradiation channels, each characterised by different neutron spectra. In the
      last two years a campaign of measurements and simulations has been performed in
      order to guarantee a better characterisation of these different fluxes and to
      meet the demands of irradiations that require precise information on these
      spectra in particular for radiobiological and microdosimetric studies.
      Experimental data on neutron fluxes have been collected analysing and measuring
      the gamma activity induced in thin target foils of different materials irradiated
      in different TRIGA experimental channels. The data on the induced gamma
      activities have been processed with the SAND II deconvolution code and finally
      compared with the spectra obtained with Monte Carlo simulations. The comparison
      between simulated and measured spectra showed a good agreement allowing a more
      precise characterisation of the neutron spectra and a validation of the adopted
      method. 

PMID- 25958413
TI  - Comparing seven mitogens with PHA-M for improved lymphocyte stimulation in
      dicentric chromosome analysis for biodosimetry.
AB  - Dicentric chromosome analysis (DCA) is the gold standard for individual radiation
      dose estimation. Two limiting factors of DCA are the time-consuming lymphocyte
      stimulation and proliferation using the lectin PHA-M and the upper dose limit of
      individual dose assessment of ~4 Gy. By measuring the mitotic index (MI), the
      authors investigated systematically whether the stimulation of lymphocytes can be
      improved after administration of alternative (and combined) mitogens. The authors
      compared the lymphocyte stimulation effectiveness of the traditionally used PHA-M
      (from Phaseolus vulgaris) with seven cited mitogens by determination of MIs: five
      lectins namely CNA (concanavalin A), PW (pokeweed), LMA (Maackia amurensis), LTV
      (T. vulgaris), PHA-L (P. vulgaris) as well as LPS (lipopolysaccharide,
      Escherichia coli) and SLO (streptolysine O, Streptococcus pyogenes) were applied.
      The conventional protocol using PHA-M for lymphocyte stimulation proved to be
      superior over lower/higher PHA-M concentrations as well as seven other mitogens
      administered either alone or combined with SLO or LPS. 

PMID- 25958414
TI  - Monte Carlo-based Spencer-Attix and Bragg-Gray tissue-to-air stopping power
      ratios for ISO beta sources.
AB  - Spencer-Attix (SA) and Bragg-Gray (BG) mass-collision-stopping-power ratios of
      tissue-to-air are calculated using a modified version of EGSnrc-based SPRRZnrc
      user-code for the International Organization for Standardization (ISO) beta
      sources such as (147)Pm, (85)Kr, (90)Sr/(90)Y and (106)Ru/(106)Rh. The ratios are
      calculated at 5 and 70 um depths along the central axis of the unit density ICRU
      4-element tissue phantom as a function of air-cavity lengths of the extrapolation
      chamber l = 0.025-0.25 cm. The study shows that the BG values are independent of
      l and agree well with the ISO-reported values for the above sources. The overall
      variation in the SA values is ~0.3% for all the investigated sources, when l is
      varied from 0.025 to 0.25 cm. As energy of the beta increases the SA stopping
      power ratio for a given cavity length decreases. For example, SA values of
      (147)Pm are higher by ~2% when compared with the corresponding values of
      (106)Ru/(106)Rh source. SA stopping-power ratios are higher than the BG stopping
      power ratios and the degree of variation depends on type of source and the value
      of l. For example, the difference is up to 0.7 % at l = 0.025 cm for the
      (90)Sr/(90)Y source.

PMID- 25958415
TI  - A case of radiation-induced generalized morphea with prominent mucin deposition
      and tenderness.
AB  - BACKGROUND: Radiation-induced morphea is a rare complication of radiation
      therapy. The affected areas are generally restricted to the radiation field or to
      the nearby surrounding area. CASE REPORT: A 67-year-old Japanese woman with a
      history of right breast cancer followed by adjuvant radiotherapy was referred our
      hospital because of 7-year history of symmetrical indurated erythematous plaques
      on her trunk. Three months after completion of irradiation, erythematous plaques
      developed on her right chest and gradually spread accompanied tenderness. She did
      not have a history of trauma to her right chest. Laboratory testing was positive
      for antinuclear antibody test at 1: 640 but negative for anti-SS-A/B, anti-U1
      RNP, anti-DNA, anti-Sm, anticentromere, anti-topoisomerase I antibodies, and
      Borrelia and cytomegalovirus infection. She had no Raynaud's phenomenon,
      sclerodactyly, or nail-fold bleeding. She did not have interstitial lung disease
      or other internal organ involvement. A biopsy specimen revealed reticular dermal
      fibrosis with thickened collagen bundles with superficial and deep perivascular
      infiltration of mononuclear cells. These findings were consistent with morphea.
      Furthermore, mucin deposition was present in the papillary dermis upon Alcian
      blue staining, which has been reported to be observed in generalized morphea.
      Consequently, a diagnosis of generalized morphea induced by radiotherapy was
      made. She had been treated with oral hydroxychloroquine sulfate, resulting in the
      resolution of tenderness but the erythematous plaques remained. CONCLUSIONS: To
      the best of our knowledge, this is the first report of radiation-induced
      generalized morphea with prominent mucin deposition. Hydroxychloroquine sulfate
      may be efficacious for radiation-induced morphea-associated tenderness.

PMID- 25958416
TI  - An assessment of facilities and services at Anganwadi centers under the
      Integrated Child Development Service scheme in Northeast District of Delhi,
      India.
AB  - OBJECTIVE: The current study was aimed to assess the facilities and services
      being provided at the Anganwadi Centres (AWCs) by the Anganwadi workers with
      regards to the norms laid down by Integrated Child development Service (ICDS)
      scheme, with special emphasis on the children of 0-6 years of age. DESIGN: Cross
      sectional study. SETTING: A resettlement colony of North-West District of Delhi,
      having a population of hundred thousand. PARTICIPANTS: A total of 41 AWCs were
      present in the study area and were included in our study. The Anganwadi workers
      at these AWCs were interviewed. MAIN OUTCOME MEASURES: The outcome measures were
      the facilities present at the AWCs and knowledge of Anganwadi workers regarding
      the services to be provided and revised supplementary nutrition norms laid down
      by ICDS. RESULTS: The AWCs in the area were covered under three projects namely
      Project A, B and C consisting of 18, 9 and 14 AWCs, respectively. The mean room
      size for all the AWCs was 108.97 +/- 62.18 square feet. A weighing machine was
      present in 29 (70.7%) of the AWCs. Growth charts for growth monitoring of
      children were present in 28 (68.3%) of AWCs. A drug kit was not present in 14
      (34.1%) of the 41 AWCs. The mean number of children of 0-3 years enrolled per AWC
      was 45.78 +/- 14.07. However, the mean number of children present at the time of
      the visit at the AWCs was 6.24 +/- 5.39. Knowledge of Anganwadi workers regarding
      revised norms for calorie and protein for beneficiaries was found to be poor.
      CONCLUSION: This study showed a lack of facilities at the AWCs and poor knowledge
      of Anganwadi workers. Thus a regular training and supportive supervision of the
      Anganwadi workers is recommended along with the availability of adequate
      facilities and infrastructures.

PMID- 25958417
TI  - Dracunculiasis eradication:  global surveillance summary,  2014.

PMID- 25958418
TI  - Monthly report on  dracunculiasis cases, January-  February 2015.

PMID- 25958419
TI  - Ernest Juvara (1870-1933) -- founder of the Surgical Anatomy School of Iasi.

PMID- 25958420
TI  - Author's reply: To PMID 24969186.

PMID- 25958421
TI  - Author's reply: To PMID 24969183.

PMID- 25958422
TI  - Research redefining adoptability could save many animals' lives.

PMID- 25958423
TI  - Bill would lift tax on veterinary student loan repayment program.

PMID- 25958424
TI  - Study: 1 in 6 veterinarians have considered suicide.

PMID- 25958425
TI  - Lawmakers seek expansion of animal welfare regulations.

PMID- 25958426
TI  - Egg rules endure challenges.

PMID- 25958427
TI  - New Salmonella serotype identified.

PMID- 25958428
TI  - Feedyard dust can include drugs, bacteria.

PMID- 25958429
TI  - NAVC kicks off the year: announcements abound at first major conference of 2015.

PMID- 25958430
TI  - APHIS plans actions  on cattle fever ticks,  screwworms.

PMID- 25958431
TI  - Advanced education increasing in popularity  but not as much salarywise.

PMID- 25958432
TI  - Kansas State establishing Center for Outcomes Research and Education.

PMID- 25958433
TI  - Trap-spay-vaccinate-release  for cats.

PMID- 25958434
TI  - Changing the culture  of antimicrobial use.

PMID- 25958435
TI  - The AVMA Task Force for Antimicrobial Stewardship in Companion Animal Practice
      responds.

PMID- 25958436
TI  - Maternity benefits  for veterinarians.

PMID- 25958437
TI  - Texas A&M University's new roads into one health.

PMID- 25958438
TI  - Behavior difficult to  reconcile with theories  of rational economic  decision
      making.

PMID- 25958439
TI  - The authors respond.

PMID- 25958440
TI  - Bring in the cat.

PMID- 25958441
TI  - The RCM makes history.

PMID- 25958442
TI  - Voicing what matters to you.

PMID- 25958444
TI  - Anti-D: getting it right.

PMID- 25958443
TI  - 'When you become a parent, you draw upon your own experience and framework, but
      if that's one of neglect and trauma, it's not much help'.

PMID- 25958445
TI  - The author's response.

PMID- 25958446
TI  - New research seeks recruits.

PMID- 25958447
TI  - Improving mental health.

PMID- 25958448
TI  - Lovely Emma.

PMID- 25958449
TI  - Facilitate a home birth.

PMID- 25958450
TI  - MSWs do matter.

PMID- 25958451
TI  - How does place of birth influence planned birth setting in subsequent
      pregnancies?

PMID- 25958452
TI  - Voicing the silence: the maternity care experiences of women who were sexually
      abused in childhood.

PMID- 25958453
TI  - IQ versus EQ.

PMID- 25958454
TI  - Experiencing normality.

PMID- 25958455
TI  - Eddie the e-midwife.

PMID- 25958456
TI  - What's changed?

PMID- 25958457
TI  - The shadow of venous thromboembolism.

PMID- 25958458
TI  - Mistaken identity.

PMID- 25958459
TI  - All change.

PMID- 25958460
TI  - [A new approach to the search for vestibuloprotectors].
AB  - The results of experimental clinical testing of the antinaupathia action of as
      new compounds, so motion sickness medications (promethazine, ikaron-1 etc.) are
      presented. Russian medication mexidol, a derivative of 3-hydroxypyridine (3-HP)
      demonstrated the ability to control motion sickness in humans and animals;
      however, unlike reference vestibuloprotector scopolamine, it does not practically
      produce side-effects. Mexidol acts through ion pathways with the involvement of
      glutamate and GABA-ergic components. Revealed 9 of new 3-HP derivates with an
      antimotion sickness effect in rats, three exceeded in efficacy mexidol, and also
      reference medications (i.e. scopolamine and promethazine). Melatonin achieves a
      better vestiboloprotective effect in rats than promethazine and melatonin-ergic
      antidepressant agomelatine through the involvement of melatonin MT1-, MT2- and
      GABA(A)-receptors. Also, combinations of melatonin with mexidol or promethazine
      possess a distinct vestibuloprotective effect, as melatonin enhances the action
      of equally mexidol and promethazine. Analysis of our results and investigations
      of other authors infer that search for potent vestibuloprotectors should be
      extended to new 3-HP derivatives and melatoninergic compounds. Individual
      medications by themselves and in combinations can become a solution to the
      problem.

PMID- 25958462
TI  - [Human body composition during extended stay in microgravity].
AB  - According to the Sprut-2 protocol, bio-impedancemetry of ISS cosmonauts was
      performed once a month and also before and after mission. Multiple non-invasive
      body measurements were carried out in 15 cosmonauts in real time. Relocation of
      extracellular liquid along the body axis led to its reduction in legs and, on the
      contrary, an increase in the abdomen. Volumes of total body liquid as well as
      intra- and extracellular liquids decreased in comparison with pre-flight levels.
      Lean body mass also became less in microgravity, whereas fat mass showed an
      increase.

PMID- 25958461
TI  - [Normal values of the major parameters of lower limb veins in Russian cosmonauts
      prior to flight and in healthy untrained subjects].
AB  - The article presents normal values of the major parameters of lower limb veins in
      cosmonauts during preparations for space flight and volunteers leading a common
      life. The authors report the results and discuss the causes for differences in
      normal leg venous parameters in these groups of subjects. Incomparability of
      measurements made in cosmonauts and common people is demonstrated. Changes in
      lower limb veins of a cosmonaut in microgravity can be evaluated only relative to
      his/her normal values of the major venous parameters (capacitance, compliance and
      filling) before flight.

PMID- 25958463
TI  - [Urine protein profile in healthy people following locomotor loading with
      changing intensity].
AB  - The paper analyzes data on how physical exercise as a standard test of
      cosmonaut's performance, affects the renal function and urine protein profile.
      The investication involved 10 normal human subjects. Following exercise, rate of
      renal excretion of proteins increased. The occurrence of 4 proteins out of 9 in
      urine did not alter and of 2 (alpha-methylacyl coenzyme A racemase and cubilin)
      increased; occurrence of 3 proteins (kallikrein-1, osteopontin and vitamin K
      dependent protein Z) decreased. Out of 24 proteins with molecular weights higher
      than albumin, 7 were detected in urine after exercise more frequently, 6 with
      same frequency as before the test and none less frequently which demonstrates
      lowered selectivity of the glomerular barrier during exercise.

PMID- 25958464
TI  - [Neuromotor apparatus in the condition of gravitational unloading: central and
      peripheral effects].
AB  - The functioning of central and peripheral structures of the gastrocnemius m.
      neuromotor apparatus was studied in rats exposed to simulated gravitational
      unloading. Gastrocnemius reflex (H) and motor (M) responses evoked by electrical
      stimulation of the sciatic nerve were measured after 7, 14, 21 and 35 days of
      tail-suspension. It was shown that thresholds of registered potentials went down
      on all days of testing; the H-amplitude rose during every testing and M-amplitude
      rose after 35 days of the gravitational unloading. Results of the experiments
      indicate changes in the functioning of motor centers that modulate properties and
      characteristics of peripheral neuromotor structures. The observed rearrangements
      can be caused by reduction of the afferent inflow.

PMID- 25958465
TI  - [Cytogenetic investigations of bone marrow cells from mice exposed onboard
      biosatellite "Bion-M1"].
AB  - The results of studying the mitotic activities and chromosomal aberrations in
      bone marrow cells from C57/BL6N mice with the help of the anaphase technique in
      12 hours after completion of the 30-day "Bion-M1" mission and ground-based
      experiment using flight equipment are presented. A statistically reliable decline
      of the mitotic activity (0.74%) was found in cells taken from the space flown
      animals. In the ground-based experiment, a statistically reliable downward trend
      in proliferative activity (1.37%) was revealed after the comparison with groups
      of vivarium control (1.46-1.53%). In both experiments mice increased the number
      of initial mitotic phases (prophase + metaphase) relative to the sum of anaphases
      and telophases. The number of aberrant mitoses grew reliably in the group of
      flight animals by 29.7%, whereas in the ground-based experiment an upward trend
      was insignificant as their number increased up to 2.3% only. In the vivarium
      controls aberrant mitoses constituted 1.75-1.8%. An increase in chromosomal
      aberrations was largely due to such abnormalities as fragments. These findings
      seem to have been a result of summation of the effects of radiation and other
      stressful factors in space flight.

PMID- 25958466
TI  - [Sequencing of low-molecular-weight DNA in blood plasma of irradiated rats].
AB  - Extracellular low-molecular-weight DNA in blood of irradiated rats was sequenced
      for the first time. The screening of sequences in the DDBJ database displayed
      homology of various parts of the rodent genome. Sequences of low-molecular-weight
      DNA in rat's plasma are enriched with G/C pairs and long interspersed elements
      relative to rat genome. DNA sequences in blood of rats irradiated at the doses of
      8 and 100 Gy have marked distinctions. Data of sequencing of extracellular DNA
      from normal humans and with pathology were analyzed. DNA sequences of irradiated
      rats differ from the human ones by a wealth of long interspersed elements. This
      new knowledge lays the foundation for development of minimally invasive
      technologies of diagnosing the probability of pathology and controlling the
      adaptive resources of people in extreme environments.

PMID- 25958467
TI  - [Cytogenetic damage to the corneal epithelium of mice due to the in vivo exposure
      to ionizing radiation with different levels of linear energy transfer].
AB  - Damages to corneal epithelium cells were studied in mice irradiated by protons
      with the energies of 10, 25, 50 and 645 MeV, 60Co gamma-quanta and accelerated
      ions of boron, carbon and neon with the energies of 7.5; 2.5 and 6.0 MeV/nucleon,
      respectively. X-rays (180 keV) were used as a standard radiation. Animals were
      exposed to a single dose in the range from 25 to 760 cGy. The mitotic index and
      aberrant mitoses were counted in corneal preparations in 24 hrs after
      irradiation. No matter the type of radiation, the mitotic index had an inverse
      dose dependence, i.e. the higher the dose, the lower the mitotic index. Exposure
      to all types of radiation resulted in a sharp increase in the number of
      chromosomal aberrations in the corneal epithelium; frequency of aberrations was a
      function of dose and type of radiation. The number of chromosomal aberrations
      displayed a peculiar direct dose dependence irrespective of type of radiation;
      however, heavy ions of carbon and boron are the most damaging to the cytogenetic
      apparatus of epithelial cells. Protons at the Bragg peak and ensuing fall, and of
      50 MeV also contribute to the production of chromosomal aberrations as compared
      with sparsely ionizing gamma- and X-rays and high-energy protons with low linear
      energy transfer. Coefficients of relative biological effectiveness were
      calculated based on the mitotic index and evidence of aberrant mitosis.

PMID- 25958468
TI  - [Analysis of the importance of cosmonaut's location and orientation onboard the
      International space station to levels of visceral irradiation during traverse of
      the region of the South Atlantic Anomaly].
AB  - Parametric analysis of absorbed radiation dose to the cosmonaut working in the
      Service module (SM) of the International space station (ISS) was made with
      allowance for anisotropy of the radiation field of the South Atlantic Anomaly.
      Calculation data show that in weakly shielded SM compartments the radiation dose
      to poorly shielded viscera may depend essentially on cosmonaut's location and
      orientation relative to the ISS shell. Difference of the lens absorbed dose can
      be as high as 5 times depending on orientation of the cosmonaut and the ISS. The
      effect is less pronounced on the deep seated hematopoietic system; however, it
      may increase up to 2.5 times during the extravehicular activities. When the
      cosmonaut is outside on the ISS SM side presented eastward, the absorbed dose can
      be affected noticeably by remoteness from the SM. At a distance less than 1.5
      meters away from the SM east side in the course of ascending circuits, the
      calculated lens dose is approximately half as compared with the situation when
      the cosmonaut is not shielded by the ISS material.

PMID- 25958469
TI  - [Effect of hypobaric hypoxia on the dehydrogenase activities of respiration and
      photosynthetic metabolism in barley seedlings].
AB  - Hypobaric hypoxia effects on enzymes of photosynthesis and respiration metabolism
      were explored in 8-day old seedlings of barley Hordeum vulgare L. in the dark or
      light. 16-hour exposure in rarified atmosphere that causes reductions of partial
      pressure of air gases and, consequently, hypobaric hypoxia (P(air) = 8.3 kappaPa,
      pO2 = 1.7 kappaPa, pCO2 = 0.003 kappaPa) up-regulated the activities of piruvate
      kinase, alcohol dehydrogenase, glucose-6-phosphate dehydrogenase and NADP x N
      glyceraldehyde phosphate dehydrogenase both in the dark and light. NAD- and NAD-N
      malate dehydrogenase activities were down-regulated. Levels of NAD- and NAD x H-
      malate dehydrogenases were decreased. Activation of the NADP-malic enzyme
      activity, invariably high activity of NADP-isocitrate dehydrogenase and growth of
      NADP x N- glyceraldehyde phosphate dehydrogenase are considered as a mechanism of
      barley seedlings adaptation to hypobaric hypoxia.

PMID- 25958470
TI  - [The perspective of buildng-up the emergency medical aid resources on the Russian
      segment of the International space station].

PMID- 25958471
TI  - The Author and the Reviewer of the Year 2014 Award by Vojnosanitetski Pregled.

PMID- 25958472
TI  - Morphometric analysis of collagen and inflammatory cells in periodontal disease.
AB  - BACKGROUND/AIM: Periodontal disease affects gingival tissue and supporting
      apparatus of the teeth leading to its decay. The aim of this study was to
      highlight and precisely determine his- tological changes in the gum tissue.
      METHODS: Gingival biopsy samples from 53 healthy and parodontopathy-affected
      patients were used. Clinical staging of the disease was performed. Tissue
      specimens were fixed and routinely processed. Sections, 5 MUm thin, were stained
      with hematoxylin and eosin, histochemical Van-Gieson for the collagen content,
      Spicer method for mast-cells and immunochemical method with anti-CD68 and anti
      CD38 for the labelling of the macrophages and plasma-cells. Morphometric analysis
      was performed by a M42 test system. RESULTS: While the disease advanced, collagen
      and fibroblast volume density decreased almost twice in the severe cases compared
      to the control ones, but a significant variation was observed within the
      investigated groups. The mast-cell number increased nearly two times, while the
      macrophage content was up to three times higher in severe parodontopathy than in
      healthy gingival tissue. However, the relative proportion of these cells stayed
      around 6% in all cases. Plasma-cells had the most prominent increase in the
      number (over 8 times) compared to the control, but again, a variation within
      investigated groups was very high. CONCLUSION: Gingival tissue destruction caused
      by inflammatory process leads to significant changes in collagen density and
      population of resident connective tissue cells. Although inflammatory cells
      dominated with the disease advancing, a high variation within the same
      investigated groups suggests fluctuation of the pathological process.

PMID- 25958473
TI  - Functional recovery of patients with ischemic cardiomyopathy treated with
      coronary artery bypass surgery and concomitant intramyocardial bone marrow
      mononuclear cell implantation--a long-term follow-up study.
AB  - BACKGROUND/AIM: Intramyocardial bone marrow mononuclear cells (BMMNC)
      implantation concomitant to coronary artery bypass grafting (CABG) surgery as an
      option for regenerative therapy in chronic ischemic heart failure was tested in a
      very few number of studies, with not consistent conclusions regarding improvement
      in left ventricular function, and with a follow-up period between 6 months and 1
      year. This study was focused on testing of the hypothesis that intramyocardial
      BMMNC implantation, concomitant to CABG surgery in ischemic cardiomyopathy
      patients, leads to better postoperative long-term results regarding the primary
      end-point of conditional status-functional capacity and the secondary endpoint of
      mortality than CABG surgery alone in a median follow-up period of 5 years.
      METHODS: A total of 30 patients with ischemic cardiomyopathy and the median left
      venticular ejection fraction (LVEF) of 35.9 +/- 4.7% were prospectively and
      randomly enrolled in a single center interventional, open labeled clinical trial
      as two groups: group I of 15 patients designated as the study group to receive
      CABG surgery and intramyocardial implantation of BMMNC and group II of 15
      patients as the control group to receive only the CABG procedure. All the
      patients in both groups received the average of 3.4 +/- 0.7 implanted coronary
      grafts, and all of them received the left internal mammary artery (LIMA) to the
      left anterior descending (LAD) and autovenous to other coronaries. RESULTS: The
      group with BMMNC and CABG had the average of 17.5 +/- 3.8 injections of BMMNC
      suspension with the average number of injected bone marrow mononuclear cells of
      70.7 +/- 32.4 x 10(6) in the total average volume of 5.7 +/- 1.5 mL. In this
      volume the average count of CD34+ and CD133+ cells was 3.96 +/- 2.77 x 10(6) and
      2.65 +/- 1.71 x 10(6), respectively. All the patients were followed up in 2.5 to
      7.5 years (median, 5 years). At the end of the follow-up period, siginificantly
      more patients from the group that received BMMNC were in the functional class I
      compared to the CABG only group (14/15 vs 5/15; p = 0.002). After 6 months the
      results on 6-minute walk test (6-MWT) were significantly different between the
      groups (435 m in the BMMNC and CABG group and 315 m in the CABG only group; p =
      0.001), and continued to be preserved and improved on the final follow-up (520 m
      in the BMMNC and CABG group vs 343 m in the CABG only group; p < 0.001).
      Cardiovascular mortality was also significantly reduced in the BMMNC and CABG
      group (p = 0.049). CONCLUSION: Implanatation of BMMNC concomitant to CABG is a
      safe and feasible procedure that demonstates not only the improved functional
      capacity but also a reduced cardiac mortality in a 5-year follow-up in patients
      with ischemic cardiomyopathy scheduled for CABG surgery.

PMID- 25958474
TI  - Influence of postoperative low-level laser therapy on the osseointegration of
      self-tapping implants in the posterior maxilla: a 6-week split-mouth clinical
      study.
AB  - BACKGROUND/AIM: Low-level laser therapy (LLLT) has been proven to stimulate bone
      repair, affecting cellular proliferation, differentiation and adhesion, and has
      shown a potential to reduce the healing time following implant placement. The aim
      of this clinical study was to investigate the influence of postoperative LLLT
      osseointegration and early success of self-tapping implants placed into low
      density bone. METHODS: Following the split-mouth design, self-tapping implants n
      = 44) were inserted in the posterior maxilla of 12 patients. One jaw side
      randomly received LLLT (test group), while the other side was placebo (control
      group). For LLLT, a 637 nm gallium-aluminum-arsenide (GaAlAs) laser (Medicolaser
      637, Technoline, Belgrade, Serbia) with an output power of 40 mW and continuous
      wave was used. Low-level laser treatment was performed immediately after the
      surgery and then repeated every day in the following 7 days. The total
      irradiation dose per treatment was 6.26 J/cm2 per implant. The study outcomes
      were: implant stability, alkaline-phosphatase (ALP) activity and early implant
      success rate. The follow-up took 6 weeks. RESULTS: Irradiated implants achieved a
      higher stability compared with controls during the entire follow-up and the
      difference reached significance in the 5th postoperative week (paired t-test, p =
      0.030). The difference in ALP activity between the groups was insignificant in
      any observation point (paired t-test, p > 0.05). The early implant success rate
      was 100%, regardless of LLLT usage. CONCLUSION: LLLT applied daily during the
      first postoperative week expressed no significant influence on the
      osseointegration of self-tapping implants placed into low density bone of the
      posterior maxilla. Placement of self-tapping macro-designed implants into low
      density bone could be a predictable therapeutic procedure with a high early
      success rate regardless of LLLT usage.

PMID- 25958475
TI  - Difference in recurrence frequencies of non-muscle-invasive-bladder tumors
      depending on optimal usage of intravesical immunotherapy of bacillus Calmette
      Guerin.
AB  - BACKGROUND/AIM: The therapy with intravesical instillation of bacillus Calmette
      Guerin (BCG) after transurethral resection (ITJR) of the tumor is the gold
      standard of treatment of non-muscle invasive bladder cancer (NMIBC). The aim of
      this study was to compare the frequencies of reccurence between a group of
      patients submitted to TUR + BCG therapy (group I) and a group of patients
      submitted only to TUR (group II). METHODS: The patients with NMIBC, a total of
      899, treated in our Institution from January 1, 2007 to March, 2013, were
      included in this study and divided into two groups: group I and group II. These
      two groups were divided into three subgroups: solitary first diagnosed tumor <= 3
      cm (SFDGT), solitary first diagnosed tumor > 3 cm and multiple first diagnosed
      tumors (MFDGT), and recedive tumors (RCT). Statistical analysis was performed by
      using chi2-test and Kolmogorov-Smirnov test. RESULTS: In the group I a total of
      133 cases had reccurence contrary to 75 in the group II, making a statistically
      highly significant difference. Analysis of recurrences through the subgroups
      revealed: in the group I SFDGT recurrence occured in 27 of the cases vs 9 cases
      in the group II; in the group I MFDGT recurrence occured in 49 of the cases vs 31
      in the group II (p < 0.001), and finally, in the group I RCT recurrence occured
      in 57 cases vs 35 cases in the group II (p < 0.001). CONCLUSION: The obtained
      results indicate no difference in the frequency of reccurence between the group I
      and group II regarding SFDGT, but a very high significant difference regarding
      those with MFDGT and RCT. These results should be taken into consideration in
      everyday clinical practise.

PMID- 25958476
TI  - Concordance of clinical and neurophysiologic diagnoses of carpal tunnel syndrome.
AB  - INTRODUCTION/AIM: Clinical presentation and neurophysiological examination are
      crucial in diagnosing carpal tunnel syndrome (CTS). The aim of this study was to
      determine sensitivity and specificity of clinical examination for diagnosing of
      CTS in relation to neurophysiological evaluation. METHODS: The sample included
      181 patients referred to the eurologist for further diagnosis of pain and
      parestesias in the arm (81 women and 100 men mean age 42 +/- 14 years and 52 +/-
      16 years, respectively). All the patients were neurophysiologicly tested.
      RESULTS: Out of 181 patients, clinical findings were considered positive for CTS
      in 37 patients. The neurophysiological findings for CTS were positive in 60
      patients. Both clinical and neurophysiological findings were positive in 31
      patients and both findings were negative in 115 patients (sensitivity 0.51;
      specificity 0.95). CONCLUSION: Low sensitivity and high specificity suggest that
      it is easier to exclude rather than to accurately diagnose CTS based on clinical
      examination alone. Thus, there is the need for neurophysiological evaluation of
      patients with complains in the arm.

PMID- 25958477
TI  - Comparative analysis of the current payment system for hospital services in
      Serbia and projected payments under diagnostic related groups system in urology.
AB  - BACKGROUND/AIM: Global budget per calendar year is a traditional method of
      funding hospitals in Serbia. Diagnose related groups (DGR) is a method of
      hospital payment based on classification of patients into groups with clinically
      similar problems and similar utilization of hospital resources. The aim of this
      study was to compare current methods of hospital services payment with the
      projected costs by DRG payment method in urology. METHODS: The data were obtained
      from the information system used in the Clinical Hospital Center "Dr. Dragisa
      Misovic"--Dedinje in Belgrade, Serbia. The implemented hospital information
      system was the main criterion for selection of healthcare institutions. The study
      included 994 randomly selected patients treated surgically and conservatively in
      2012. RESULTS: Average costs under the current payment method were slightly
      higher than those projected by DRG, however, the variability was twice as high
      (54,111 +/- 69,789 compared to 53,434 +/- 32,509, p < 0.001) respectively. The
      univariate analysis showed that the highest correlation with the current payment
      method as well as with the projected one by DRG was observed in relation to the
      number of days of hospitalization (rho = 0.842, p < 0.001, and rho = 0.637, p <
      0.001, respectively). Multivariate regression models confirmed the influence of
      the number of hospitalization days to costs under the current payment system
      (beta = 0.843, p < 0.001) as well as under the projected DRG payment system (beta
      = 0.737, p < 0.001). The same predictor was crucial for the difference in the
      current payment method and the pro- jected DRG payment methods (beta = 0.501, p <
      0.001). CONCLUSION: Payment under the DRG system is administratively more complex
      because it requires detailed and standardized coding of diagnoses and procedures,
      as well as the information on the average consumption of resources (costs) per
      DRG. Given that aggregate costs of treatment under two hospital payment methods
      compared in the study are not significantly different, the focus on minor
      surgeries both under the current hospital payment method and under the introduced
      DRG system would be far more cost-effective for a hospital as great variations in
      treatment performance (reductions of days of hospitalization and complications),
      and consequently invoiced amounts would be reduced.

PMID- 25958478
TI  - A 5-year retrospective analysis of necrotizing fasciitis--a single center
      experiences.
AB  - BACKGROUND/AIM: Necrotizing fasciitis (NF) is usually an acute infection of
      superficial fascia with rapid progression in around soft tissue. If not promptly
      recognized and aggressively treated NF usualy leads to sepsis and multiorgan
      failure with fatal outcome, thus early diagnosis and prompt surgical treatment
      are crucial for healing of these patients. The aim of this article was to
      evaluate the clinical presentation of all patients with acute NF diagnosed and
      treated in surgical clinics of Clinical Center of Vojvodina, Novi Sad, Serbia.
      METHODS: The medical records of patients treated for acute NF localized on a
      different parts of the body in Clinical Center of Vojvodina, Novi Sad, Serbia,
      during a 5-year period (from January 2008 to December 2012) were retrospectively
      evaluated. This study enrolled patients admitted via Emergency Center of
      Vojvodina with the diagnosis of acute NF either as the primary diagnosis or with
      the diagnosis at discharge after surgical treatment. RESULTS: During a 5-year
      period there were 216 patients with final diagnosis of acute NF. Most of our
      patients (140-64.81%) were admitted with the initial diagnosis of cellulitis,
      abscesses, phlegmons or sepsis. Unfortunately, the clinical symptoms of acute NF
      were atypical at time of initial examination. Pain and swelling of the affected
      localization were the most presented bias of symptoms (183-84.72%). The majority
      of our patients were male (164-75.92%). Among the 216 patients, the most common
      pre-existing single factor was drug abuse (39-18.05%), followed by obesity (38
      17.59%) and diabetes mellitus (31-14.35%). Trauma was most common etiological
      factor (22-10.8%) in infected wounds, followed by abdominal (15-6.94%) and
      orthopedic (11-5.09%) surgical intervention. In the present study idiopathic
      acute NF was diagnosed in 22 (10.18%) patients and more than one etiological
      factor were diagnosed in 20 (9.25%) patients. The majority of our pa- tients had
      type I acute NF (172-79.62%) with Streptococcal species as the most common
      microorganism (125-71.02%). The most common localization was an extremity (151
      69.90%). The minority of our patients had head and neck lo- calization of
      infection (7-3.24%). Surgical treatment was performed in all the patients and
      most of them (183-84.72%) received the first surgery within 24 h. Other patients
      (23-10.64%) received operation after stabilization of general status or after
      getting the diagnosis of acute NF (unclear diagnosis on admission). During
      hospitalization, the most common complication among our patients was sepsis (156
      72.22%). The mortality rate was 14.35%. CONCLUSION: Acute NF is a rare but very
      difficult and sometimes life-threatening disease of superficial fascia and around
      soft tissue. If acute NF is suspected, early radical excision of all the affected
      tissue with exploration and excision of superficial fascia with pathological and
      microbiological assessment are most significant for treatment. Appropriate
      antibiotics and intensive care set ting to manage other organ failure of NF are
      recommended at the same time with surgery.

PMID- 25958479
TI  - Gingivitis and periodontitis in children and adolescents suffering from type 1
      diabetes mellitus.

PMID- 25958480
TI  - Intravenous fat emulsion in clinical practice: nutrient and antidote.

PMID- 25958481
TI  - Epidermolysis bullosa of the esophagus--a case report.
AB  - INTRODUCTION: Epidermolysis bullosa is a rare skin disease which could be
      hereditary or acquired with autoimmune mechanism. Even though it is known that
      epidermolysis bullosa appears on various mucosa, the esophagus is seldom
      affected. CASE REPORT: We reported 19-year-old female patient who had been
      admitted due to dysphagia and odyno- phagia to solid food. Erythematous changes
      with bullae and excoriations could be found on the hands, feet, elbows and knees.
      The patient underwent barium swallow which revealed retaining of contrast in the
      valleculas and piriform recesses, as well as dilatation of meso- and hypopharynx-
      upper achalasia syndrome. The cause was stenosis at the level of upper functional
      sphincter of the esophagus, 10 mm in length with benign apperance. Small leakage
      of contrast into the trachea was visible at the later stage of examination,
      concomitant with volume load of the pharynx. Bullae were not detected. The whole
      esophagus was fairly uniformly stenotic and had fibrotic appearance. CONCLUSION:
      The au- thors emphasize that barium swallow can provide sufficient information
      regarding stenosis, dynamics of the disorder, as well as the stage of the
      disease. Furthermore, we highlight the importance of providing a complete
      diagnostic strategy in all dermatology patients who could simultaneously have
      mucous changes.

PMID- 25958482
TI  - Efficacy of long-acting somatostatin analogs in recurrent variceal bleeding in a
      patient with pre-hepatic portal vein thrombosis.
AB  - INTRODUCTION: Bleeding from esophageal varices is a serious medical problem
      because of the risk of recurrent bleeding and high mortality rate (17-54%).
      Gastroesophageal varices develop in 50% of cirrhotic patients with portal
      hypertension, but can also develop in other pre- or post-hepatic causes of portal
      hypertension. CASE REPORT: We reported a 48-year-old female patient with portal
      hy- pertension caused by mesenterial vein thrombosis due to congenital
      thrombophilia. The patient was hospitalized several times be- cause of recurrent
      gastroesophageal bleeding. Thrombosis of portal, lienal and mesenteric veins was
      diagnosed using multislice computed tomography (MSCT) angiography. Sclerotherapy
      and/or variceal ligation could not be used due to variceal size and distribution.
      Beta blockers were ineffective. Balloon tamponade and octreotide were used in
      each massive bleeding episode. Carvedilol therapy was introduced but rebleeding
      occured. Surgical treatment was considered a high risk procedure due to massive
      thrombosis of mesenterial veins, patient's general condition and high risk of
      postoperative thrombotic events. Thus, long-acting somatostatin analogue-
      Sandostatin LAR was initiated at a dose of 30 mg im/month. The patient responded
      to the therapy well and variceal bleeding did not occur for the following 3
      months. After 3 months another episode of gastric variceal hemorrhage occurred
      and surgical treatment was reconsidered. Total gastrectomy was performed in order
      to prevent repeated bleeding from large gastric varices and the patient recovered
      successfully, and after 1 year is symptom-free. Conclusion. Long-lasting
      somatostatin analogue was used for the first time in treatment of
      gastroesophageal variceal hemorrhage in the patient with prehepatic portal
      hypertension. It was effective as temporary therapeutic option allowing the
      improvement of the patients general condition and adequate planning of elective
      surgical procedure. Futher reports are needed in order to compare efficacy in
      treatment of patients with variceal bleeding, where poor outcome is expected.

PMID- 25958483
TI  - Secondary surgical management of suprachoroidal hemorrhage during pars plana
      vitrectomy.
AB  - INTRODUCTION: Suprachoroidal hemorrhage (SCH) is one of the most feared and
      devastating complications of intraocular surgery. Intraoperative SCH is defined
      as sudden hemorrhagic swelling of the choroid which develops at time of
      intraocular surgery, and is associated with expulsion of some or all of the
      intraocular contents. CASE REPORT: A 56-year-old man was admitted to our Clinic
      with bullose retinal detachment in the left eye. Intraoperatively, during the
      substitution of perfluorocarbone liquid (PFCL) with silicone oil, which is very
      rare situation, a sudden loss of red reflex happened and SCH was recognized as
      the cause. No attempt was made to drain the suprachoroidal blood. After 3 weeks
      the patient was scheduled for pars plana vitrectomy. Initial drainage of liqufied
      blood was made through a sclerotomy port during pars plana inferotemporally.
      Massive epiretinal proliferation with funnel shaped retinal detachment was solved
      during vitrectomy and internal tampo- nade with silicone oil was done.
      Postoperative visual aquity was 2/60 on the third postoperative day. CONCLUSION:
      Although suprachoroidal hemorrhage is one of most feared and devastating
      complications ofintraocular surgery, it might have relatively good prognosis with
      proper preoperative, intraoperative and postoperative management

PMID- 25958484
TI  - Massive right atrial myxoma with dyspnea at rest in an elderly patient: a case
      report.
AB  - INTRODUCTION: Primary heart tumors are extremely rare and myxoma is the most
      common type of these tumors. Although intra-atrial presentation is a predilection
      place, right atrial localization is atypical. The symptom triad is characteristic
      in the clinical presentation of the tumor: embolic complication, intracardiac
      blood flow obstruction and systemic manifestations like elevated erythrocyte
      sedimentation rate, fever, anemia, body weight loss. CASE REPORT: We presented an
      elderly female patient with massive myxoma in the right atrium, 77 x 44 mm in
      diameter, which filled the entire right atrium and spread into the right
      ventricle, causing the tricuspid valve obstruction and dyspnea. It was visualized
      by transthoracic echocardiography and small and insignificant pericardial
      effusion was also seen. After surgical removal of the tumor, the patient remained
      without any symptoms and pericardial effusion. CONCLUSION: Tumors of the right
      heart have to be considered in the differential diagnosis of unexplained dyspnea
      in elderly patients. Transthoracic echocardiography is certainly necessary and
      mostly available diagnostic tool that can be of great help in diagnosing heart
      tumor as well as planning cardiac surgery, as it provides in most cases excellent
      visualization of the tumor and its relationship with other parts of the heart.

PMID- 25958485
TI  - Hypercalcemic type of small cell carcinoma of the ovary.
AB  - INTRODUCTION: Extrapulmonary small cell carcinoma is a rare, prognostically bad
      tumor category. Primary, it can be localized in every organ, even in the ovary,
      where, due to its clinical specificities, it represents a challenge in diagnosis,
      as well as in therapy. Small cell ovarian carcinoma (SCOC) is biologically very
      aggressive malignant tumor of unknown histogenesis. We presented a rare case of
      SCOC with hypercalcemia of aggressive course and fatal outcome in a
      postmenopausal woman at International Federation of Gynecology and Obstetrics
      (FIGO) Ia stage. CASE REPORT: A 60-year-old woman, Caucasian, came to the doctor
      because of discomfort in the lower abdomen and pain of greater intensity in last
      few days. Ultrasound examination and CT scan of the abdomen confirmed the
      presence of large adnexal masses of cystic-solid appearance with the largest
      diameter of 13 cm, regular structure of the other gynecological organs, without
      verifying the existence of metastatic deposits. All the results of laboratory
      analysis gave normal values, except for calcium, which was elevated. Explorative
      laparotomy with complete hysterectomy, bilateral salpingo-oophorectomy,
      dissection of lymph nodes and omentectomy were conducted. Based on
      pathohistological analysis of the operative material, SCOC at FIGO Ia stage was
      diag- nosed. No complications were observed in a postsurgery period and after 10
      days the patient was discharged in a good condition and with normal calcemia. The
      treatment was continued with concurrent radiotherapy and chemotherapy. However,
      in spite of overall treatment, the disease progressed, and the patient died of
      disseminated metastatic disease, 26 months after the diagnosis. CONCLUSION: Small
      cell carcinoma localized in the ovary is generally a tumor category with bad
      prognosis depending on the stage of the disease.

PMID- 25958486
TI  - Design and analysis of vertical-channel gallium nitride (GaN) junctionless
      nanowire transistors (JNT).
AB  - Vertical-channel gallium nitride (GaN) junctionless nanowire transistor (JNT) has
      been designed and characterized by technology computer-aided design (TCAD)
      simulations. Various characteristics such as wide bandgap, strong polariztion
      field, and high electron velocity make GaN one of the attractive materials in
      advanced electronics in recent times. Nanowire-structured GaN can be applicable
      to various transistors for enhanced electrical performances by its geometrical
      feature. In this paper, we analyze the direct-current (DC) characteristics
      depending on various channel doping concentrations (N(ch)) and nanowire radii
      (R(NW)). Furthermore, the radio-frequency (RF) characteristics under optimized
      conditions are extracted by small-signal equivalent circuit modeling. For the
      optimally designed vertical GaN JNT demonstrated on-state current (I(on)) of 345
      MUA/MUm and off-state current (I(off)) of 3.7 x 10(-18) A/MUm with a threshold
      voltage (V(t)) of 0.22 V, and subthreshold swing (S) of 68 mV/dec. Besides, f(T)
      and f(max) under different operating conditions (gate voltage, V(GS)) have been
      obtained.

PMID- 25958487
TI  - Heteromaterial gate tunneling field-effect transistor for high-speed and radio
      frequency applications.
AB  - We propose a tunneling field-effect transistor (TFET) with a heteromaterial (HM)
      gate not only for low standby power (LSTP) applications, which TFETs are
      genuinely suitable for, but also for high-speed performance by properly adjusting
      intrinsic gate capacitance (C(gg)). As a result of simulations in this work, the
      HM-gate TFET showed better subthreshold characteristics (smaller S) at an
      appropriate threshold voltage (V(th)) for LSTP applications, enhancing tunneling
      probability by modulating the difference in the metal workfunction (phi(m))
      between the source-side gate (S-gate) and the drain-side gate (D-gate). Further,
      the C(gg) of HM-gate TFET were extracted and compared against that of
      conventional TFETs having gates with various phi(m)'s. Since lower C(gg) can be
      formed by high phi(m) in the D-gate, the HM-gate TFET has an excellent cut-off
      frequency (f(T)) and intrinsic delay time (tau) associated with the C(gg). We
      confirmed that the HM-gate TFET proposed in this work achieves superb performance
      for LSTP applications as well as high-frequency operations.

PMID- 25958488
TI  - Comparison of recessed gate-head structures on normally-off AlGaN/GaN high
      electron-mobility transistor performance.
AB  - In this work, different gate-head structures have been compared in the context of
      AlGaN/GaN-based high-electron-mobility transistors (HEMTs). Field-plate (FP)
      technology self-aligned to the gate electrode leads to various gate-head
      structures, most likely gamma (gammaF)-gate, camel (see symbol)-gate, and
      mushroom-shaped (T)-gate. In-depth comparison of recessed gate-head structures
      demonstrated that key performance metrics such as transconductance, output
      current, and breakdown voltage are better with the T-gate head structure. The
      recessed T-gate with its one arm toward the source side not only reduces the
      source-access resistance (R(g) +R(gs)), but also minimizes the source-side
      dispersion and current leakage, resulting in high transconductance (G(m)) and
      output current (I(DS)). At the same time, the other arm toward the drain-side
      reduces the drain-side dispersion and tends to distribute electric field peaks
      uniformly, resulting in high breakdown voltage (V(BR)). DC and RF analysis showed
      that the recessed T-gate FP-HEMT is a suitable candidate not only for high
      frequency operation, but also for high-power applications.

PMID- 25958489
TI  - Effective contact resistance of zinc-tin oxide-based thin film transistors.
AB  - We investigated different source/drain (S/D) electrode materials in thin-film
      transistors (TFTs) based on amorphous zinc-tin oxide (ZTO) semiconductors. The
      transfer length, channel conductance, and effective contact resistance between
      the S/D electrodes and the a-ZTO channel layer were examined. Total ON resistance
      (R(T)), transfer length (L(T)) and effective contact resistance (R(c-eff)) were
      extracted by the well-known transmission-line method (TLM) using a series of TFTs
      with different channel lengths. When the width of ZTO channel layer was fixed as
      50 MUm, the lengths were varying from 10 to 50 MUm. The channel layer and S/D
      electrode were defined by lift-off process and for the S/D electrodes, indium-tin
      oxide (ITO), Cu, and Mo were used. The resistivity and work function values of
      electrode materials were considered when selected as candidates for S/D
      electrodes of ZTO-TFTs. The results showed that the ZTO-TFTs with Mo S/D
      electrodes had the lowest effective contact resistance indicating that ZTO-TFTs
      with Mo electrodes have better electrical performance compared to others.

PMID- 25958490
TI  - Effect of grain boundary on the field-effect mobility of microrod single crystal
      organic transistors.
AB  - High-performance microrod single crystal organic transistors based on a p-type
      2,7-dioctyl[1]benzothieno[3,2-b][1]benzothiophene (C8-BTBT) semiconductor are
      fabricated and the effects of grain boundaries on the carrier transport have been
      investigated. The spin-coating of C8-BTBT and subsequent solvent vapor annealing
      process enabled the formation of organic single crystals with high aspect ratio
      in the range of 10 - 20. It was found that the organic field-effect transistors
      (OFETs) based on these single crystals yield a field-effect mobility and an
      on/off current ratio of 8.04 cm2/Vs and > 10(5), respectively. However, single
      crystal OFETs with a kink, in which two single crystals are fused together,
      exhibited a noticeable drop of field-effect mobility, and we claim that this
      phenomenon results from the carrier scattering at the grain boundary.

PMID- 25958491
TI  - Contact-enhanced transparent silver nanowire network for all solution-based top
      contact metal-oxide thin-film transistors.
AB  - In this paper, we investigate contact-enhanced transparent silver nanowire (Ag
      NW) network for solution-processed metal-oxide thin-film transistors (TFTs).
      Mechanical roll pressing was applied to a bar-coated Ag NW film to enhance the
      inter-nanowire connectivity. As a result, the sheet resistance of the Ag NW film
      was decreased from 119.5 psi/square to 92.4 psi/square, and more stable and
      enhanced TFT characteristics were achieved when the roll-pressed Ag NW was
      employed as source/drain electrodes. In addition, a non-acidic wet etching method
      was developed to pattern the Ag NW electrodes to construct top-contact geometry
      indium-gallium-zinc oxide TFTs. From the results, it is believed that the
      mechanical roll pressing and non-acidic wet etching method may be utilized in
      realizing all solution-based transparent metal-oxide TFTs.

PMID- 25958492
TI  - Effect of Ta addition of co-sputtered amorphous tantalum indium zinc oxide thin
      film transistors with bias stability.
AB  - In this work, we have fabricated thin film transistors (TFTs) using amorphous
      tantalum indium zinc oxide (a-TaInZnO) channels by the co-sputtering process. The
      effects of incorporating tantalum on the InZnO material were investigated using
      Hall-effect measurement results, and electrical characteristics. We also found
      that the carrier densities of thin films and the transistor on-off currents were
      greatly influenced by the composition of tantalum addition. Ta ions have strong
      affinity to oxygen and so suppress the formation of free electron carriers inthin
      films; they play an important role in enhancing the electrical characteristic due
      to their high oxygen bonding ability. The electrical characteristics of the
      optimized TFTs shows a field effect mobility of 3.67 cm2 V(-1) s(-1), a threshold
      voltage of 1.28 V, an on/off ratio of 1.1 x 10(8), and a subthreshold swing of
      480 mV/dec. Under gate bias stress conditions, the TaInZnO TFTs showed lower
      shift in threshold voltage shifts.

PMID- 25958493
TI  - Low-voltage-operated organic one-time programmable memory using printed organic
      thin-film transistors and antifuse capacitors.
AB  - We demonstrate an organic one-time programmable memory cell formed entirely at
      plastic-compatible temperatures. All the processes are performed at below 130
      degrees C. Our memory cell consists of a printed organic transistor and an
      organic capacitor. Inkjet-printed organic transistors are fabricated by using
      high-k polymer dielectric blends comprising poly(vinylidenefluoride
      trifluoroethylene) [P(VDF-TrFE)] and poly(methyl methacrylate) (PMMA) for low
      voltage operation. P(NDI2OD-T2) transistors have a high field-effect mobility of
      0.2 cm2/Vs and a low operation gate voltage of less than 10 V. The operation
      voltage effectively decreases owing to the high permittivity of the P(VDF
      TrFE):PMMA blended film. The data in the memory cell are programmed by
      electrically breaking the organic capacitor. The organic capacitor acts like an
      antifuse capacitor, because it is initially open, and it becomes permanently
      short-circuited by applying a high voltage. The organic memory cells are
      programmed with 4 V, and they are read out with 2 V. The memory data are read out
      by sensing the current in the memory cell. The printed organic one-time
      programmable memory is suitable for applications storing small amount of data,
      such as low-cost radio-frequency identification (RFID) tag.

PMID- 25958494
TI  - Parameter modeling for nanopore lonic field effect transistors in 3-D device
      simulation.
AB  - An Ion Field Effect Transistor (IFET) with nanopore structure was modeled in a
      conventional 3-dimensional (3-D) device simulator to understand current-voltage
      (I-V) characteristics and underlying physics of the device. Since the nanopore
      was filled with positive ions (K+) ions due to the negative interface charge on
      the insulator surface and negative gate bias condition, we could successfully
      simulate the IFET structure using modified p-type silicon to mimic KCl solution.
      We used p-type silicon with a doping concentration of 6.022 x 10(16) cm(-3) which
      has the same concentration of positive carriers (hole) as in 10(-4) M KCl. By
      controlling gate electric field effect on the mobility, the I-V curves obtained
      by the parameter modeling matched very well with the measured data. In addition,
      the decrease of [V(th)] with increasing V(DS) was physically analyzed.

PMID- 25958496
TI  - Resistive switching characteristics of manganese oxide nanoparticle assembly with
      crossbar arrays.
AB  - The fabrication of 3 x 3 crossbar arrays measuring 20 MUm in width was
      demonstrated. The bipolar resistive switching characteristics in manganese oxide
      nanoparticles were investigated in the crossbar structure of top electrode
      (Au)/nanoparticle assembly/bottom electrode (Ti) on SiO2/Si substrate. The
      monodisperse manganese oxide nanoparticles measuring 13 nm in diameter were
      chemically synthesized by thermal decomposition of manganese acetate in the
      presence of oleic acid at high temperature. The nanoparticles were assembled as a
      layer measuring 30 nm thick by repeated dip-coating and annealing steps. The
      Au/nanoparticle assembly/Ti devices performed the bipolar behavior associated
      with the formation and sequential rupture of multiple conducting filaments in
      applying bias on Au electrode. When the voltage was swept from to +5 V to the Au
      top electrode, the reset voltage was observed at - 4.4 V. As the applied voltage
      swept from 0 to -5 V, the set voltage occurred at (-) -1.8 V.

PMID- 25958495
TI  - Carrier-transport mechanism of Er-silicide Schottky contacts to strained-silicon
      on-insulator and silicon-on-insulator.
AB  - The current-voltage characteristics and the carrier-transport mechanism of the Er
      silicide (ErSi1.7) Schottky contacts to strained-silicon-on-insulator (sSOI) and
      silicon-on-insulator (SOI) were investigated. Barrier heights of 0.74 eV and 0.82
      eV were obtained for the sSOI and SOI structures, respectively. The barrier
      height of the sSOI structure was observed to be lower than that of the SoI
      structure despite the formation of a Schottky contact using the same metal
      silicide. The sSOI structure exhibited better rectification and higher current
      level than the SOI structure, which could be associated with a reduction in the
      band gap of Si caused by strain. The generation-recombination mechanism was found
      to be dominant in the forward bias for both structures. Carrier generation along
      with the Poole-Frenkel mechanism dominated the reverse-biased current in the SOI
      structure. The saturation tendency of the reverse leakage current in the sSOI
      structure could be attributed to strain-induced defects at the interface in non
      lattice-matched structures.

PMID- 25958497
TI  - Effect of oxidizable electrode material on resistive switching characteristics of
      ZnO(x)S(1-x) films.
AB  - We investigate the memory characteristics of ZnO(x(S(1-x) based resistive
      switching random access memory (ReRAM) devices with Al and Pt bottom electrodes
      (BEs). Both the ReRAM devices with Al and Pt BEs exhibit unipolar resistive
      switching behaviors, regardless of the materials of the BEs. The ratios of the
      high resistance state (HRS) to the low resistance state (LRS) of the Au/annealed
      ZnO(x)S(1-x)/Al and the Au/annealed ZnO(x)S(1-x)/Pt devices are more than 10(6)
      and 10(4), respectively. The HRS depends more significantly on the material of
      the BE than the LRS. The resistance in the HRS of the device with the Al BE is
      more stable in the endurance characteristics and higher in magnitude than that of
      the device with the Pt BE. For an anealed ZnO(x)S(1-x)/Al film, the oxygen signal
      in the auger depth profile shows the formation of an AIO(x) layer at the
      interface between the annealed ZnO(x)S(1-x) layer and the Al BE. The difference
      between the memory characteristics of the annealed ZnO(x)S(1-x) devices with the
      Al and Pt BEs is explained with the presence or absence of the oxidized layers
      formed in the interfaces between the annealed ZnO(x)S(1-x) films and the BEs.

PMID- 25958498
TI  - Resistive switching characteristics of HfO2-based memory devices on flexible
      plastics.
AB  - In this study, we examine the characteristics of HfO2-based resistive switching
      random access memory (ReRAM) devices on flexible plastics. The Pt/HfO2/Au ReRAM
      devices exhibit the unipolar resistive switching behaviors caused by the
      conducting filaments. From the Auger depth profiles of the HfO2 thin film, it is
      confirmed that the relatively lower oxygen content in the interface of the bottom
      electrode is responsible for the resistive switching by oxygen vacancies. And the
      unipolar resistive switching behaviors are analyzed from the C-V characteristics
      in which negative and positive capacitances are measured in the low-resistance
      state and the high-resistance state, respectively. The devices have a high on/off
      ratio of 10(4) and the excellent retention properties even after a continuous
      bending test of two thousand cycles. The correlation between the device size and
      the memory characteristics is investigated as well. A relatively smaller-sized
      device having a higher on/off ratio operates at a higher voltage than a
      relatively larger-sized device.

PMID- 25958500
TI  - Electrical characteristics of metal oxide based multi-layer vertical resistive
      switching memories.
AB  - The electrical properties of vertical resistive switching random access memories
      (VRRAMs) were investigated to enhance their device performance by using a
      stochastic method based on the generation and the rupture probability of the
      conductive filaments (CFs) together with a tunneling model. The carrier transport
      mechanisms were dominantly attributed to the tunneling current between the CFs
      and the electrode. Carrier transport mechanisms of the high resistance state
      current were dominantly attributed to the direct tunneling current between the
      electrode and the CFs locating at nearest the electrode. The simulated forming
      voltages of the VRRAMs were in reasonable agreement with the experimental data.
      The low resistance/high resistance state current ratio of the VRRAMs was improved
      due to an increase in the distance between the CFs and the electrode of the
      VRRAMs with a barrier material after a reset operation. These results can help
      understanding electrical characteristics and optimal structures of the VRRAMs.

PMID- 25958499
TI  - Composition-ratio influence on resistive switching behavior of solution-processed
      InGaZnO-based thin-film.
AB  - The influence of composition ratio on the bipolar resistive switching behavior of
      resistive switching memory devices based on amorphous indium-gallium-zinc-oxide
      (a-IGZO) using the spin-coating process was investigated. To study the
      stoichiometric effects of the a-IGZO films on device characteristics, four
      devices with In/Ga/Zn stoichiometries of 1:1:1, 3:1:1, 1:3:1, and 1:1:3 were
      fabricated and characterized. The 3:1:1 film showed an ohmic behavior and the
      1:1:3 film showed a rectifying switching behavior. The current-voltage
      characteristics of the a-IGZO films with stoichiometries of 1:1:1 and 1:3:1,
      however, showed a bipolar resistive memory switching behavior. We found that the
      three-fold increase in the gallium content ratio reduces the reset voltage from 
      0.9 to - 0.4 V and enhances the current ratio of high to low resistive states
      from 0.7 x 10(1) to 3 x 10(1). Our results show that the increase in the Ga
      composition ratio in the a-IGZO-based ReRAM cells effectively improves the device
      performance and reliability by increasing the initial defect density in the a
      IGZO films.

PMID- 25958501
TI  - Micro-size antenna structure with vertical nanowires for wireless power
      transmission and communication.
AB  - For biomedical implanted devices, a wireless power or a signal transmission is
      essential to protect an infection and to enhance durability. In this study, we
      present a magnetic induction technique for a power transmission without any wire
      connection between transmitter (Tx) and receiver (Rx) in a micro scale. Due to a
      micro size effect of a flat spiral coil, a magnetic inductance is not high. To
      enhance the magnetic inductance, a three dimensional magnetic core is added to an
      antenna structure, which is consisted of ZnO nano wires coated by a nickel (Ni)
      layer. ZnO nano wires easily supply a large effective surface area with a
      vertical structural effect to the magnetic core structure, which induces a higher
      magnetic inductance with a ferro-magnetic material Ni. The magnetic induction
      antenna with the magnetic core shows a high inductance value, a low reflection
      power and a strong power transmission. The power transmission efficiencies are
      tested under the air and the water medium are almost the same values, so that the
      magnetic induction technique is quite proper to body implanted systems.

PMID- 25958502
TI  - Effect of the fixed charge distribution on the mobility degradation of the high-k
      dielectric MOSFETs.
AB  - The effects of the fixed charge in the high-k dielectric layer near a SiO2 layer
      on the mobility degradation mechanisms were investigated by using a full three
      dimensional technology computer aided design simulator. The electron density and
      the electric field in the channel region were significantly affected due to the
      fixed charge in the SiO2 layer and the interface between SiO2 and HfO2 layers.
      The electron density in a channel increased with increasing fixed charge
      concentration, resulting in a decrease in the mobility. The variation of the
      vertical electric field due to the fixed charge in the high-k dielectric layer
      was attributed to the degradation effect. The electric field in a channel
      deteriorated the electron mobility due to the electron attraction to the
      heterointerface of the substrate and the interfacial layer. The mobility
      decreased with increasing fixed charge concentration near the heterointerface of
      the substrate and the SiO2 layer. The effect of the fixed charge distribution on
      the mobility degradation of the high-k dielectric MOSFETs was described on the
      simulation results.

PMID- 25958503
TI  - Mobility degradation mechanisms of MOSFETs with a high-k dielectric layer.
AB  - The electrical characteristics of MOSFETs with a high-k dielectric layer were
      simulated by using a full three-dimensional technology computer-aided design
      simulator. The MOSFETs leakage current increased when their size decreased. The
      mobility variation mechanisms due to the polarization variation with the positive
      fixed charges in the high-k dielectric layer and with the negative trap charges
      in the SiO2 layer were clarified by using a modified mobility model of the
      universal model taking into account remote phonon scattering effects. The induced
      polarization in the high-k dielectric layer was dominantly attributed to the
      magnitude and the polarity of the charges in an interfacial layer. The mobility
      degradation was dominantly attributed to the polarization effects. The mobility
      values of the channel region in the MOSFETs, calculated by using the modified
      mobility model, were in reasonable agreement with their real mobility magnitudes.
      This result improves the enhancement of the electrical characteristic of the
      MOSFETs with a high-k layer.

PMID- 25958504
TI  - A reliable extraction method for source and drain series resistances in silicon
      nanowire metal-oxide-semiconductor field-effect-transistors (MOSFETs) based on
      radio-frequency analysis.
AB  - This paper presents a new extraction method for source and drain (S/D) series
      resistances of silicon nanowire (SNW) metal-oxide-semiconductor field-effect
      transistors (MOSFETs) based on small-signal radio-frequency (RF) analysis. The
      proposed method can be applied to the extraction of S/D series resistances for
      SNW MOSFETs with finite off-state channel resistance as well as gate bias
      dependent on-state resistive components realized by 3-dimensional (3-D) device
      simulation. The series resistances as a function of frequency and gate voltage
      are presented and compared with the results obtained by an existing method with
      infinite off-state channel resistance model. The accuracy of the newly proposed
      parameter extraction method has been successfully verified by Z22- and Y
      parameters up to 100 GHz operation frequency.

PMID- 25958505
TI  - (E)-2,2'dibromo-7,7'-bis(diphenylamino)-9,9' bifluorenylidene as a new electron
      acceptor for organic photovoltaic cells.
AB  - (E)-2,2'-Dibromo-7,7'-bis(diphenylamino)-9,9'-bifluorenylidene (BDPABF) was
      synthesized as a new non-fullerene-type electron acceptor for organic
      photovoltaic cells. The UV-visible absorption spectra of BDPABF showed two main
      bands at 319 and 474 nm in a chloroform solution and 320 and 481 nm as a solid
      thin film. The optical band gap of BDPABF was determined to be 2.34 eV by
      measuring the onset absorption wavelength of the solid thin film. The ionization
      potential of BDPABF was determined to be 5.59 eV using photoelectron
      spectroscopy. The measured lowest unoccupied molecular orbital energy level of
      BDPABF was - 3.25 eV. Its electron-accepting ability was investigated through a
      Stern-Volmer quenching experiment. The intensity of the photoluminescence of P3HT
      dramatically decreased upon the addition of BDPABF. The measured Stern-Volmer
      quenching constant was 5.3 x 10(4) M(-1). Photovoltaic devices were fabricated
      using P3HT as the electron donor and BDPABF as the electron acceptor at various
      composition ratios. The optimized device showed a maximum power conversion
      efficiency of 0.27% with an open-circuit voltage of 0.71 V, short-circuit current
      density of 1.29 mA/cm2, and fill factor of 0.29 after thermal annealing at 100
      degrees C for 5 min.

PMID- 25958506
TI  - Enhanced light extraction from organic light emitting diodes by micrometer-sized
      buckles.
AB  - The simple ways for creating buckled structures to enhance the light extraction
      from OLED devices have been investigated. The buckling instability was observed
      when the ITO was deposited on the polymer-coated glass by sputtering. The
      textured surface of the ITO layer after buckling was characterized by an atomic
      force microscopy. The wavelength of the resulting buckled structure was a few
      microns in a size. The buckling was easily modified by adjusting the pressure of
      the argon gas during the sputter deposition of ITO layer. The buckled ITO layer
      was used for fabricating OLED devices. The reduction in the operating voltage for
      the OLED with the buckled ITO anode was observed. The current and power
      efficiencies for the OLED with the buckeld structure were 5% and 44% higher than
      those for the conventional OLED. The broader light distribution was observed in
      the OLED with buckling when the angular dependence of the light intensity was
      measured.

PMID- 25958507
TI  - Blue inorganic light emitting diode on flexible polyimide substrate using laser
      lift-off process.
AB  - The fabrication process for the blue GaN inorganic light emitting diode (ILED) on
      flexible polyimide (PI) substrate by laser lift off (LLO) method was
      demonstrated. The GaN epi-structure was grown on patterned sapphire wafer. GaN
      samples were temporary bonded with polyimide substrate by flexible silver epoxy.
      Separation of the whole GaN LED film from GaN/sapphire wafer was accomplished
      using a single KrF excimer (248 nm) laser pulse directed through the transparent
      sapphire wafer. Device fabrication was carried out on both rigid silicon and
      flexible polyimide substrate, and I-V performance for both devices was measured.
      The optimized LLO process for the whole GaN LED film transfer would be applicable
      in flexible LED applications without compromising electrical properties.

PMID- 25958508
TI  - Attachment of metal nanoparticles to SnO2 nanowires for enhancement of gas
      sensing properties.
AB  - We fabricated SnO2/cobalt (Co) core-shell nanowires by means of a two-step
      process, for their application as chemical sensors. For Co-functionalization, we
      synthesized SnO2-Co core-shell nanowires by the sputtering deposition of Co
      layers on the surface of networked SnO2 nanowires, subsequently transforming the
      continuous Co-shell layers into crystalline islands by thermal heating. While
      scanning electron microscopy (SEM) images of annealed core-shell nanowires
      exhibited a rough surface, transmission electron microscopy (TEM) images revealed
      that the roughness is related to the agglomeration of the sputtered Co layer. The
      X-ray diffraction (XRD) pattern and lattice-resolved TEM images coincidentally
      indicated that the agglomerated particles are comprised of a hexagonal Co phase.
      The NO2 sensing test revealed that the sensor response was enhanced by decoration
      with Co nanoparticles. In addition, both response and recovery times tended to
      decrease as a result of the Co-functionalization. This indicates that the Co
      functionalized SnO2 nanowire sensors can be used to sense gases at very low
      concentrations. We discussed possible mechanisms for enhancing sensor properties
      by Co-functionalization. The NO2 gas sensing test demonstrated the ability of the
      Co-functionalization to provide higher sensitivity, shorter response time, and
      shorter recovery time than would bare SnO2 nanowires.

PMID- 25958509
TI  - Electrochemically decorated ZnTe nanodots on single-walled carbon nanotubes for
      room-temperature NO2 sensor application.
AB  - A gas sensor with ZnTe nanodot-modified single-walled carbon nanotubes (SWCNTs)
      is demonstrated for NO2 detection at room temperature. ZnTe nanodots are
      electrochemically deposited in an aqueous solution containing ZnSO4, TeO2 and
      citrate. A deposition potential range of ZnTe formation of -0.65 to -0.9 V is
      determined by cyclic voltammetry, and an intermetallic ZnTe compound is formed at
      above 50 degrees C bath. SWCNT-based sensors show the highly sensitive response
      down to 1 ppm NO2 gas at room temperature. In particular, the sensitivity of ZnTe
      nanodot-modified SWCNTs is increased by 6 times as compared to that of pristine
      SWCNT sensors. A selectivity test of SWCNT-ZnTe nanodots sensors is carried out
      with ammonia gas (NH3) and methanol vapor (MeOH), and the result confirms an
      excellent selectivity to NO2 gas.

PMID- 25958510
TI  - A novel synthesis route for Pt-loaded SnO2 nanofibers and their sensing
      properties.
AB  - A novel one-pot synthesis method for Pt-loaded SnO2 nanofibers is reported on the
      basis of the sol-gel and electrospinning-combined process. The ultraviolet
      illumination was used for in-situ growth of Pt nanoparticles in the
      electrospinning solution. The sensing capability of pure SnO2 nanofibers was
      significantly improved by loading Pt nanoparticles. The Pt-loaded SnO2 nanofibers
      showed a good selectivity to toluene gas. The optimization of Pt amount in SnO2
      nanofibers was essential to obtain best sensing performances. The one-pot
      synthesis method developed in this work may extend the use of oxide nanofibers in
      chemical gas sensors.

PMID- 25958511
TI  - Electrochemical migration behavior of a fine-pitch IC substrate by alternating
      current.
AB  - Electrochemical migration properties of fine pitch chip-on-flex (COF) for
      displays were investigated by a water drop test and scanning electron microscope
      with energy dispersive spectroscopy. While the time to failure due to ECM is less
      than 1 s at a direct current (DC) bias of 10 V, it is approximately 330 s at an
      alternating current (AC) bias of 10 V 10 Hz and approximately 3,940 s at 240 Hz.
      The ECM failure mode due to AC bias appears to be caused by limitations on the
      degree of ion diffusion and relatively small changes of the pH, unlike the DC
      bias case.

PMID- 25958512
TI  - Very high cycle fatigue behavior of SAE52100 bearing steel by ultrasonic
      nanocrystalline surface modification.
AB  - In this paper, the SAE52100 bearing steel contained large quantities of cementite
      dispersed in ferrite matrix was subjected to the ultrasonic nanocrystalline
      surface modification (UNSM) treatment that aims for the extension of fatigue
      life. The microstructure and fatigue life of the untreated and treated specimens
      were studied by using electron backscattered diffraction (EBSD) and transmission
      electron microscopy (TEM), and a developed ultra-high cycle fatigue test (UFT).
      After UNSM treatment, the coarse ferrite grains (- 10 MUm) were refined to
      nanosize (- 200 nm), therefore, nanostructured surface layers were fabricated.
      Meanwhile, in the deformed layer, the number density and area fraction of
      cementite were increased up to - 400% and - 550%, respectively, which increased
      with the decrease in depth from the topmost treated surface. The improvement of
      hardness (from 200 Hv to 280 Hv) and high cycles fatigue strength by - 10% were
      considered the contribution of the developed nanostructure in the UNSM treated
      specimen.

PMID- 25958513
TI  - Interfacial magnetic anisotropy of Co90Zr10 on Pt layer.
AB  - Spin Transfer Torque (STT) is of great interest in data writing scheme for the
      Magneto-resistive Random Access Memory (MRAM) using Magnetic Tunnel Junction
      (MTJ). Scalability for high density memory requires ferromagnetic electrodes
      having the perpendicular magnetic easy axis. We investigated CoZr as the
      ferromagnetic electrode. It is observed that interfacial magnetic anisotropy is
      preferred perpendicular to the plane with thickness dependence on the interfaces
      with Pt layer. The anisotropy energy (K(u)) with thickness dependence shows a
      change of magnetic-easy-axis direction from perpendicular to in-plane around 1.2
      nm of CoZr. The interfacial anisotropy (K(i)) as the directly related parameters
      to switching and thermal stability, are estimated as 1.64 erg/cm2 from CoZr/Pt
      multilayered system.

PMID- 25958514
TI  - The preparation of fluorine doped cadmium oxide thin film by sol-gel process.
AB  - During the several decades, CdO thin film has attracted many attentions as a
      candidate for the transparent conducting electrodes due to its high electrical
      conductivity and high optical transmittance. Various dopants such as F, In, Al,
      Sn, and Cr have been used to improve the optical and electrical properties of the
      film. Generally, the optical and electrical property of the thin film is
      dependent on its oxidation state, the amount of dopant materials, and the
      fabrication process. In this study, fluorine doped CdO thin films were prepared
      by using sol-gel process with various atomic ratios of Cd:F, and their electrical
      and optical properties were investigated. The precursor solution for sol-gel film
      was prepared with pH 5 and pH 8, and the film was annealed at 350 degrees C. X
      ray diffraction pattern confirmed the cubic CdO:F phase formation, and the 10%
      fluorine doped film prepared with pH 8 precursor solution showed the lowest
      resistivity of 0.01574 Omega cm.

PMID- 25958515
TI  - Preparation of poly(BMA-co-MMA) particles by soap-free emulsion polymerization
      and its optical properties as photonic crystals.
AB  - Narrowly dispersed poly(BMA-co-MMA) and PBMA latices with particle diameters
      ranging within 216-435 nm were synthesized successfully by surfactant-free
      emulsion polymerization with KPS and AIBA. The average particle diameter and
      particle size distribution, average molecular weight and its distribution, glass
      transition temperature, reflectance spectra in visible wavelength, and refractive
      indices for the respective poly(BMA-co-MMA) latices and their photonic crystals
      were systematically investigated in terms of BMA/MMA ratio, BMA content,
      polymerization temperature, and DVB effect. The rate of polymerization increased
      with increasing MMA concentration in BMA/MMA ratio. The particle diameter
      increased with BMA concentration in BMA/MMA ratio. The molecular weight increased
      with BMA concentration in BMA/MMA ratio and monomer concentration. The drying of
      the latices offered self-assembled shiny colloidal crystal films showing the
      characteristic structural colors in visible wavelength. All the poly(BMA-co-MMA)
      latices prepared in the study were fallen within the range of photonic grade
      microspheres. The reflectance measurement on the colloidal photonic crystals
      having different particle diameters clearly exhibited narrow stopbands. The
      reflection maxima (lambda(max)) measured in this study were well close to the
      lambda(max) calculated, derived from the Bragg's equation. The refractive indices
      of poly(BMA-co-MMA) photonic crystals were found to be almost same as the
      theoretical values and increased proportionally from 1.50 to 1.57 with BMA
      content in BMA/MMA ratios. It was, thus, found that the optical reflectance
      properties of the poly(BMA-co-MMA) colloidal photonic crystals can be controlled
      easily by adjusting the reaction conditions and BMA/MMA ratio in soap-free
      emulsion copolymerization of BMA and MMA.

PMID- 25958516
TI  - Temporal, thermal, and light stability of continuously tunable cholesteric liquid
      crystal laser array.
AB  - Fine-structured polymerized cholesteric liquid crystal (PCLC) wedge laser devices
      have been realized, with high fine spatial tunability of the lasing wavelength.
      With resolution less than 0.3 nm in a broad spectral range, more than one hundred
      laser lines could be obtained in a PCLC cell without extra devices. For practical
      device application, we studied the stability of the device in detail over time,
      and in response to strong external light sources, and thermal perturbation. The
      PCLC wedge cells had good temporal stability for 1 year and showed good stability
      for strong perturbations, with the lasing wavelength shifting less than 1 nm,
      while the laser peak intensities decreased by up to 34%, and the high energy band
      edge of the photonic band gap (PBG) was red shifted 3 nm by temperature
      perturbation. However, when we consider the entire lasing spectrum for the PCLC
      cell, the 1-nm wavelength shift may not matter. Although the laser peak
      intensities were decreased by up to 34% in total for all of the perturbation
      cases, the remaining 34% laser peak intensity is considerable extent to make use.
      This good stability of the PCLC laser device is due to the polymerization of the
      CLC by UV curing. This study will be helpful for practical CLC laser device
      development.

PMID- 25958517
TI  - Eu(3+)-doped gadolinium oxide nanoparticles synthesized by chemical
      coprecipitation predicted by thermodynamic modeling.
AB  - Thermodynamic modeling of the Gd(3+)-Eu(3+)-O(2-)-CO3(2-)-Cl- system has been
      adopted as a rational approach to establish routes to the better synthesis
      conditions for pure phase Eu(3+)-doped Gd2O3 nanoparticles. Quantitative analyses
      of the different reaction equilibria involved in the coprecipitation of Gd2(CO3)3
      and Eu2(CO3)3 x 3H2O from aqueous solutions have been used to determine the
      optimum synthesis conditions. The characterization and photoluminescence spectra
      of Gd2O3 nanoparticles doped with Eu3+ activator ions at the concentrations of 1,
      2, 3, 4 and 5 mol% synthesized by urea-based homogeneous coprecipitation are
      presented. The surface of the as-prepared mixture of Gd2(CO3)3 and Eu2(CO3)3 x
      3H2O particles are coated with silica to avoid the agglomeration followed by
      annealing the carbonate precursors at 800 degrees C for 3 hours. Subsequently,
      the silica shell is removed with an alkali solution resulting in well
      crystallized Eu(3+)-doped Gd2O3 nanoparticles. X-ray diffraction (XRD) results
      show that all the diffraction peaks are well indexed to the cubic Gd2O3 with high
      crystallinity. The photoluminescence spectra exhibit a characteristic f-f
      transition band that corresponds to Eu3+. The sharp red emission at 616 nm
      corresponds to the transition identified as 5D0 __7F2. Both the emission
      intensity at 616 nm and asymmetry factor of [I(5D0 --> 7F2)/I(5D0 --> 7F1)]
      exhibit clearly Eu(3+)-doping concentration-dependent luminescence behaviors. The
      rather fast decay time is closely correlated to the proper occupation of the Eu3+
      activator ions in the C2 sites of the Gd2O3 cage, resulting in strong dependence
      on small changes of the total electric density and defect density. Thus, the best
      concentration of Eu3+ activator ions for the maximum brightness are the 3 mol%
      Eu(3+)-doped Gd2O3 at 5D0 --> 7F2 because it shows the longest decay time and
      more luminescent intensity than the other doping concentrations.

PMID- 25958519
TI  - Scattering matrix analysis for evaluating the photocurrent in hydrogenated
      amorphous-silicon-based thin film solar cells.
AB  - A scattering matrix (S-matrix) analysis method was developed for evaluating
      hydrogenated amorphous silicon (a-Si:H)-based thin film solar cells. In this
      approach, light wave vectors A and B represent the incoming and outgoing
      behaviors of the incident solar light, respectively, in terms of coherent wave
      and incoherent intensity components. The S-matrix determines the relation between
      A and B according to optical effects such as reflection and transmission, as
      described by the Fresnel equations, scattering at the boundary surfaces, or
      scattering within the propagation medium, as described by the Beer-Lambert law
      and the change in the phase of the propagating light wave. This matrix can be
      used to evaluate the behavior of angle-incident coherent and incoherent light
      simultaneously, and takes into account not only the light scattering process at
      material boundaries (haze effects) but also nonlinear optical processes within
      the material. The optical parameters in the S-matrix were determined by modeling
      both a 2%-gallium-doped zinc oxide transparent conducting oxide and germanium
      compounded a-Si:H (a-SiGe:H). Using the S-matrix equations, the photocurrent for
      an a-Si:H/a-SiGe:H tandem cell and the optical loss in semitransparent a-Si:H
      solar cells for use in building-integrated photovoltaic applications were
      analyzed. The developed S-matrix method can also be used as a general analysis
      tool for various thin film solar cells.

PMID- 25958518
TI  - Light conversion efficiency of top-emitting organic light-emitting diode
      structure.
AB  - Top-emitting organic light-emitting diodes (OLEDs) with a microcavity structure
      are presented in this paper. We performed a finite element (FE) analysis of a
      trilayer OLED that was inserted between the reflective layer and the semi
      reflective layer of a device. We carried out an optical analysis of this OLED
      device and calculated the optimal width between the reflective layer and the semi
      reflective layer to consider the microcavity effect. Our simulation revealed that
      the thickness of each layer can affect the recombination rate at the emission
      layer. We used five OLED devices. Device A is a reference device with a 42.5 nm
      hole transport layer (HTL), a 15 nm emission layer (EML) and a 45 nm electron
      transport layer (ETL). We varied the thickness of the HTL of Device A to 20 nm
      and 65 nm, and designated these devices as Device B and Device C, respectively.
      We also varied the thickness of the ETL of Device A to 20 nm and 65 nm, and
      designated these devices as Device D and Device E, respectively. As the thickness
      of the HTL and the ETL are decreased, a higher recombination rate is achieved.
      However, the highest recombination rate does not necessarily correspond to the
      highest external quantum efficiency (EQE) owing to the resonance effect. Our
      simulation revealed that the overall thickness of the device seems to be a more
      significant factor owing to the path of light.

PMID- 25958520
TI  - Semitransparent Ni/Ag/Ni electrode for use as anode in flexible red
      phosphorescent organic light-emitting diodes.
AB  - We suggested that Ni/Ag/Ni semitransparent electrodes for the exchange of indium
      tin-oxide (ITO) electrode, which is the most commonly used as a transparent
      electrode in spite of the structural defects, limited supply of indium, and
      toxic, could be apply on flexible Organic Light-Emitting Diodes (OLEDs). Red
      phosphorescent OLEDs (PHOLEDs) using different types of electrodes as ITO and
      various conditions of Ni/Ag/Ni electrode were fabricated and analyzed. The
      electrical and optical properties of device using Ni/Ag/Ni electrode were
      improved than that of devices on ITO glass substrate at the 10,000 cd/m2
      criterion due to the micro-cavity effect even though their transmittance has
      lower than ITO glass. In addition, we also fabricated red PHOLEDs of same
      structure on Ni/Ag/Ni flexible substrate of various conditions. As a result,
      flexible red PHOLED showed competitive characteristics compared to the device on
      a glass substrate. Therefore, this study could be suggested to additional
      research on flexible OLEDs display and light applications for ITO-free
      fabrication.

PMID- 25958521
TI  - G-s0 mode converter with lateral gold mirrors for nano-plasmonic integrated
      circuits.
AB  - We propose a waveguide-typed plasmonic mode converter with lateral gold mirrors
      (LGMs) at a wavelength of 1.55 MUm. The 17.5 MUm-long gap-s0 mode converter (G-s0
      MC) is composed of an input 4.5 MUm-wide insulator-metal-insulator-metal
      insulator waveguide (IMIMI-W) and an output 2.0 MUm-wide metal-insulator-metal
      waveguide (MIM-W) with LGMs connected by a laterally tapered (LT) IMIMI-W with
      LGMs. The strip thicknesses of the IMIMI-Ws and MIM-W are 20 nm and 50 nm,
      respectively. The 12.0 MUm-long LGMs with 1.5 MUm thickness are located beside
      the LT-IMIMI-W and MIM-W. All metals in the IMIMI-Ws, MIM-W, and LGMs are
      designed with gold. A low-loss polymer is used for the 30 MUm-thick upper and
      lower cladding layers. The thickness of the central insulator in both the IMIMI
      Ws and MIM-W was designed to be 500 nm. The input Ss0 mode with the size of -5.9
      MUm x 4.8 MUm is converted to the output G-s0 mode with the size of 1.1 MUm x 0.5
      MUm. The total loss of the G-s0 MC, including conversion loss, is -6.96 dB in
      simulation. The proposed G-s0 MC may be potentially useful for bridging micro- to
      nano-plasmonic integrated circuits.

PMID- 25958522
TI  - Luminescence properties of nanosized Y3Al5O12Ce3+ phosphor synthesized by liquid
      phase precursor method.
AB  - A novel liquid-phase precursor (LPP) method using precursor nanoparticles (PNs)
      is proposed to synthesize yttrium aluminum garnet nano-sized phosphor
      (Y3Al5O12:Ce3+, nano-YAG:Ce) at 1100-1500 degrees C for 5 h. The influences of
      the heat-treatment and morphology properties of the PNs on the luminescence
      properties of the nano-YAG:Ce phosphor were investigated. Nano-YAG:Ce phosphor
      with better morphology and high luminescence efficiency was obtained with heat
      treatment of PNs at 1200 degrees C. With more heat treatment, the phosphor
      particles agglomerated more, and the emission intensity increased. The broad
      photoluminescence excitation (PLE) and photoluminescence (PL) spectra of the nano
      YAG:Ce phosphor were centered at 341 nm and 466 nm, respectively, due to the 4f -
      > 5d energy transition. The nonsymmetrical emission spectra range of 470-750 nm
      was centered at 529.2 nm due to the 5d --> 4f energy transition of Ce3+. The nano
      YAG:Ce, and micro-YAG:Ce phosphors synthesized by the LPP method using precursor
      microparticles (PMs) and PNs were investigated and compared.

PMID- 25958523
TI  - Synthesis and optical characteristics of yttrium-doped zinc oxide nanorod arrays
      grown by hydrothermal method.
AB  - Yttrium-doped ZnO (YZO) nanorods were synthesized by hydrothermal growth on a
      quartz substrate with various post-annealing temperatures. To investigate the
      effects of post-annealing on the optical properties and parameters of the
      nanorods, X-ray diffractometry (XRD), photoluminescence (PL) measurement, and
      ultraviolet (UV)-visible spectroscopy were used. From the XRD investigation, the
      full width at half maximum (FWHM) and the dislocation density of the nanorods was
      found to increase with an increase in the post-annealing temperature. In the PL
      spectra, the intensity of the near band edge (NBE) emission peak in the UV region
      also increases with an increase in the temperature of post-annealing. The deep
      level emission (DLE) peak in the visible region changes with various post
      annealing temperatures, and its intensity increases remarkably with post
      annealing at 800 degrees C. In this paper, changes in the optical parameters of
      the nanorods caused by variation in the behavior of Y during post-annealing was
      investigated, with properties such as absorption coefficients, refractive
      indices, and dispersion parameters being obtained from transmittance and
      reflectance analysis.

PMID- 25958524
TI  - Performance improvement of green phosphorescent organic light emitting diodes
      with partial bulk heterojunctioned emitting layer.
AB  - Green phosphorescent organic light emitting diodes (PHOLEDs) were developed using
      a mixed layer system. They were fabricated with 4,4'-N,N'-dicarbazolyl-biphenyl
      (CBP) and typical charge transporting materials, which are 4,4'-bis[N-(naphthyl)
      N-phenylamino]biphenyl (NPB) as a hole transporting material and 1,3,5-tris(N
      phenylbenzimidazole-2-yl)benzene (TPBi) as an electron transporting material,
      mixed at each interface in a stacked organic layer to reduce the hole injection
      barrier and extend the recombination zone. We introduced a mixed layer for the
      hole transporting layer side, the electron transporting layer side, and on both
      sides to make a bulk heterojunction. This reduced the driving voltage, and the
      luminous efficiency (LE) was increased to 500 cd/m2. The optimized device showed
      a maximum LE of 59.87 cd/A and a maximum external quantum efficiency of 17.52%.

PMID- 25958525
TI  - Electrical impedance characterization of cell growth on interdigitated
      microelectrode array.
AB  - Electrical cell-substrate impedance sensing is a method for label-free and real
      time monitoring of biological cells, which has been increasingly employed in the
      diagnostic and pharmaceutical industries. In this study, we fabricated an
      interdigitated electrode (IDE) array, which consists of 10 fingers, with a length
      of 1.2 mm, width of 50 MUm, spacing of 50 MUm, and thickness of 75 nm. The
      impedance spectra of the fabricated IDE were measured without or with cells in
      the frequency range of 100 Hz to 100 kHz using a lock-in amplifier based system
      and characterized by equivalent circuit modelling. Regarding the total impedance
      as a series resistance (R) and capacitance (C) model, R and C parameters were
      traced at a selected frequency during cell growth. It was able to monitor cell
      adherence and proliferation dependent on the behaviours and characteristics of
      cells on the fabricated IDE array by monitoring RC parameters. The degree of
      changes in RC value during cell growth was dependent on the type of cells used.

PMID- 25958526
TI  - Effect of strain relaxation in InGaN/GaN multi-quantum wells with self-assembled
      Pt nanoclusters.
AB  - We report effect of the strain relaxation in InGaN/GaN multi-quantum well (MQW)
      structures grown on platinum nanocluster-coated sapphire substrate (PNSS) by
      metal organic chemical vapor deposition. The photoluminescence (PL) intensity of
      InGaN/GaN MQWs on PNSS was significantly enhanced compared to that of the
      InGaN/GaN MQWs on flat sapphire substrate due to the reduction of defect density
      and residual strain by self-assembled Pt nanoclusters. We confirmed the reduction
      of strain-induced piezoelectric field by the power dependence of the PL in
      InGaN/GaN MQWs on PNSS. Cathodoluminescence shows that a large bright area with
      overall strong peak intensity is attributed to the suppression of In
      inhomogeneity and strain relaxation in InGaN/GaN MQWs on PNSS. Based on these
      results, we suggest that the self-assembled Pt nanocluster can be applied to
      increase the quantum efficiency through improved crystal quality and internal
      strain relaxation in MQWs.

PMID- 25958527
TI  - Luminance enhancement of color stabilized organic light-emitting devices with an
      active layer containing CdSe/CdS/ZnS core/shell/shell quantum dots.
AB  - Organic light-emitting devices (OLEDs) with a 1,3-bis(9-carbazolyl)benzene (mCP)
      or a (9-(3-(9 H-carbazol-9-yl)phenyl)-9 H-carbazol-3-yl)-diphenylphosphine oxide
      (mCPPO1) layer containing CdSe/CdS/ZnS quantum dots (QDs) were fabricated. The
      average diameter of core/shell/shell QDs, as determined from transmission
      electron microscopy measurements, was approximately 7 nm. The photoluminescence
      spectrum for the CdSe/CdS/ZnS QDs showed a dominant exciton peak. Current
      densities as functions of the voltage showed that the turn-on voltage of the OLED
      with an mCP layer containing QDs was as small as 5 V, and the luminances as
      functions of the voltage showed that the luminance of the OLED with an mCP layer
      containing QDs was much larger than that of the OLED with an mCPPO1 layer
      containing QDs. Electroluminescence spectra for OLEDs with an mCP layer
      containing QDs showed that the dominant exciton peaks corresponding to the QDs
      were located at almost the same positions, regardless of the applied voltage.
      These results help to understand the electrical and optical properties of OLEDs
      with an mCP or an mCPPO1 layer containing CdSe/CdS/ZnS core/shell/shell QDs.

PMID- 25958528
TI  - Targeted gene delivery via N-acetylglucosamine receptor mediated endocytosis.
AB  - Receptor-mediated endocytosis is a promising approach of gene delivery into the
      target cells via receptor-ligand interaction. Vimentins at the cell surface are
      recently known to bind N-acetylglucosamine (GlcNAc) residue, therefore, the cell
      surfaces of vimentin-expressing cells could be targeted by using the GlcNAc
      residue as a specific ligand for receptor-mediated gene delivery. Here, we have
      developed polymeric gene delivery vectors, based on poly(ethylene oxide)(PEO) and
      poly(aspartamide), namely poly[(aspartamide)(diethylenetriamine)]-b-[PEO
      (GlcNAc)] (PADPG) and poly[(aspartamide)(diethylenetriamine)]-b-[PEO] (PADP) to
      elucidate the efficiency of GlcNAc ligand for gene delivery through receptor
      mediated endocytosis. To determine the efficiency of these polymeric vectors for
      specific gene delivery, the DNA condensation ability of PADPG and PADP and the
      subsequent formation of polymeric nanoparticles were confirmed by gel retardation
      assay and transmission electron microscopy respectively. Both PADPG and PADP had
      lower cytotoxicity than polyethylenimine 25 K (PEI 25 K). However, their
      transfection efficiency was comparatively lower than PEI 25 K due to hydrophilic
      property of PEO in the vectors. To observe the stability of polymeric
      nanoparticles, the transfection of PADPG and PADP was carried out in the presence
      of serum. Favorably, the interfering effect of serum on the transfection
      efficiency of PADPG and PADP was also very low. Finally, when the cell
      specificity of these polymeric vectors was investigated, PADPG had high gene
      transfection in vimentin-expressing cells than vimentin-deficiency cells. The
      high transfection efficiency of PADPG was attributed to the GlcNAc in the
      polymeric vector which interact specifically with vimentin in the cells for the
      receptor-mediated endocytosis. The competitive inhibition assay further proved
      the receptor-mediated endocytosis of PADPG. Thus, this study demonstrates that
      conjugation of GlcNAc is an effective and rational way to prepare a suitable
      vector for targeted gene delivery to vimentin-expressing cells.

PMID- 25958529
TI  - Protective effects of poly(lactic-co-glycolic acid) nanoparticles loaded with
      erythropoietin stabilized by sodium cholate against glutamate-induced
      neurotoxicity.
AB  - The final aim of this study was to confirm the neuroprotective effects of
      recombinant human erythropoietin (rhEPO)-loaded poly(lactic-co-glycolic acid)
      (PLGA) nanoparticles stabilized by sodium cholate (rhEPO-Ch-NP) and compare their
      effects with those of rhEPO using an in vitro model of cerebral ischemia.
      Glutamate-induced excitotoxic damage on SH-SY5Y cells, a human neuroblastoma cell
      line, with or without rhEPO-Ch-NPs was quantitatively evaluated. The rhEPO-Ch-NPs
      were carefully prepared using a water-in-oil-in-water (w/o/w) emulsion solvent
      evaporation technique with PLGA, sodium cholate hydrate, and ethyl acetate. The
      rhEPO-Ch-NPs were fully characterized by both transmission electron microscopy
      (TEM) and differential scanning calorimetry (DSC). In addition, significant
      intracellular uptake of these particles was monitored by confocal microscopy.
      Notably, the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT)
      assay and nuclear changes observed by 4',6-diamidino-2-phenylindole (DAPI)
      staining in SH-SY5Y cells demonstrated that rhEPO-Ch-NPs were safer at any
      concentration investigated and rescued more neuronal cells, while preserving
      normocytic features against glutamate-induced excitotoxic damages compared to
      rhEPO.

PMID- 25958530
TI  - Surface morphology of nanotube formed Ti alloy by electrochemical methods.
AB  - In order to investigate the surface morphology of nanotube formed Ti alloy by
      electrochemical methods, the Ti-6Al-4V alloys for dental implant were used in
      this study. Heat treatment was carried out at 800 degrees C for 1 hour and then
      water quenching in argon atmosphere, that will be have a specimen name of 800 WQ.
      The formation of nanotube structure was conducted by electrochemical method on Ti
      6Al-4V alloy in mixed electrolytes at 30 V for 1 hour. Microstructure of beta
      phases showed dot-like structures at non-treated Ti-6Al-4V alloy, and needle-like
      in equiaxed structure from treated the alloy at 800 WQ. In non-treated Ti-6Al-4V
      alloy case, nanotubes only exhibited at alpha phase region with dissolved V-oxide
      area of beta phase. However, in the case of 800 WQ, nanotubes of Ti-6Al-4V alloy
      exhibited at both alpha and betaphase region. Electrochemical corrosion studies
      showed that the nanotubular alloy of 800 WQ possesses slightly higher corrosion
      resistance than that of non-treated nanotubular alloy.

PMID- 25958531
TI  - Strong modification of spontaneous emission rate in nanorod light-emitting diode
      structures.
AB  - This study investigates the characteristics of modifications in spontaneous
      emission (SE) from GaN-based nanorod light-emitting diode (LED) structures using
      the three-dimensional finite-difference time-domain method. The simulated nanorod
      LED structure is assumed to be enclosed by perfect conductors and includes InGaN
      multiple-quantum-well active layers emitting at 500 nm. In the simulation, the
      modification of the SE rate is calculated as the structural parameters of
      nanorods are varied. The SE rate is found to depend strongly on the radius of
      nanorods. Large enhancement of the SE rate is observed when the resonant modes
      are formed inside the nanorod cavity. For both the transverse-electric and
      transverse-magnetic modes, the SE rate of nanorod LED structures can be enhanced
      by more than six times when the radius or height of the nanorod is optimally
      chosen. This large increase in the SE rate can lead to considerable increase in
      the internal quantum efficiency of LEDs, making nanorod structures prime
      candidates for future high-efficiency LEDs than can overcome the efficiency limit
      of current LED structures.

PMID- 25958532
TI  - Optical properties of ultra-thin (< 30 nm) GaN layers on c-sapphire substrates
      with different initial growth conditions measured by surface-plasmon enhanced
      Raman scattering.
AB  - We have carried out surface-plasmon enhanced Raman spectroscopy (SERS) on 30 nm
      thick GaN samples grown at various temperatures, in order to investigate the
      properties of ultra thin GaN films on sapphire. We found that the properties,
      such as the strain and the free-carrier density of the thin layers, were
      sensitively affected by the growth temperatures. Our results show that SERS, by
      selectively enhancing the Raman signal near the surface, can be a very useful
      technique to investigate the optical properties of ultra-thin GaN films and their
      initial growth mode.

PMID- 25958533
TI  - Characterization of early-stage amyloid aggregates by incorporating extrinsic
      fluorescence and atomic force microscopy.
AB  - Amyloid-beta (Abeta) oligomers are nanosized bio-assemblies that cause
      Alzheimer's disease. Characterizing early-stage Abeta aggregates becomes an
      important issue because it is a prerequisite in exploring small molecule
      inhibitors that bind to Abeta oligomers. Of special interest are efficient
      screening systems that characterize the Abeta oligomer size with respect to the
      aging time. In this work, highly sensitive fluorescence techniques and atomic
      force microscopy (AFM) were employed to investigate the size determination of
      Abeta and screening of small molecule inhibitors. A solvatochromic dye, 1
      anilinonaphthalene-8-sulfonic acid (ANS), was used as an extrinsic fluorophore to
      monitor the growth mechanism of the Abeta aggregates. Then, the time-resolved
      fluorescence anisotropy method was employed to estimate the hydrodynamic size of
      Abeta oligomers. Finally, AFM was used to characterize the Abeta oligomer size in
      the absence and presence of potential inhibitors. We present that the combination
      of such three experimental techniques is an excellent way to detect the early
      stage of Abeta aggregation and to screen small molecule inhibitors.

PMID- 25958534
TI  - Neuroprotective effect of estradiol-loaded poly(lactic-co-glycolic acid)
      nanoparticles on glutamate-induced excitotoxic neuronal death.
AB  - Different concentrations of estradiol (E2)-loaded poly(lactic-co-glycolic acid)
      (PLGA) nanoparticles (E2-PLGA-NPs) were synthesized using the emulsion-diffusion
      method. Transmission electron microscopy results showed that the average particle
      size of E2-PLGA-NPs was 98 +/- 1.9 nm when stabilized with polyvinyl alcohol and
      103 +/- 4.9 nm when stabilized with Tween-80. Fourier transform-infrared
      spectroscopy with diamond attenuated total reflectance was used to identify the
      presence or absence of E2 molecules in PLGA nanocapsules. Cell proliferation was
      assessed after treating SH-SY5Y neuroblastoma cells with 1 nM-1 MUM of E2 and E2
      PLGA-NPs. The neuroprotective efficacy against glutamate-induced excitotoxicity
      was also investigated in SH-SY5Y neuroblastoma cells. Neuroprotection was greater
      in E2-PLGA-NP-treated cells than in cells treated with the same concentration of
      E2. Furthermore, E2- and E2-PLGA-NP-treated cells expressed more p-ERK1/2 and p
      CREB than cells treated with glutamate only. Moreover, the expression of p-ERK1/2
      was higher than that of p-CREB. In this study, p-ERK1/2 had a greater influence
      on the neuroprotective effect of E2 and E2-PLGA-NPs than p-CREB.

PMID- 25958535
TI  - Cell viability, adhesion and function of RAW 264.7 macrophages on fluorinated
      xerogel-derived nitric oxide permeable membrane for the application of cellular
      sensing.
AB  - Organically modified xerogels have an advantage over gas sensing applications due
      to their open, rigid structure and hydrophobicity. Here we evaluated the
      biocompatibility of xerogel-derived nitric oxide (NO) permeable membranes
      modified with fluorinated functional groups for application in cellular sensing
      by growing RAW 264.7 macrophages on them. We examined the cell viability,
      adhesion and growth of RAW 264.7 macrophages on NO permselective membrane and
      other cell-adhesive matrices, poly L-lysine and collagen. The surface roughness
      of each membrane was obtained from topographic atomic force microscopy (AFM)
      images. In addition, we measured the level of NO release of RAW 264.7 macrophages
      by lipopolysaccharide (LPS) stimulation using a Griess assay to confirm the
      function of cells. The fluorinated xerogel-derived membrane had a very smooth
      surface with rms roughness 2.1 A and did not show cytotoxic effects in RAW 264.7
      macrophages. As a result, the morphology and function of adhering RAW 264.7
      macrophage showed no differences from those of other cell-adhesive membranes.
      Finally, we successfully detected NO release in RAW 264.7 macrophages stimulated
      by LPS, using a planar-type xerogel-derived NO sensor. Therefore, we suggest that
      fluorinated xerogel-derived membrane could be used as both a NO permeable and
      cell-adhesive membrane for cellular sensing applications.

PMID- 25958537
TI  - Two-dimensional TiO2 honeycomb structure for enhanced light extraction from
      polymer light-emitting diodes.
AB  - We have demonstrated the preparation of an ordered hole pattern via a simple
      colloidal assembly technique and a sol-gel process without the use of any special
      equipment to enhance light extraction from polymer light-emitting diodes (LEDs).
      From two-dimensional (2D) polystyrene (PS) colloidal crystals, 2D TiO2 honeycomb
      structures were easily obtained after depositing TiO(x) sol solution onto the
      colloidal crystals by a doctor blade technique and removing the PS colloidal
      particles. In order to optimize the thickness of the deposited TiO(x) materials
      for fabricating 2D TiO2 honeycomb structures, the concentration of the TiO(x) sol
      solution was controlled. By applying the 2D TiO2 honeycomb structure on the
      backside of the glass substrate, the efficiency of a polymer LED, compared to the
      device without the structure, was increased without a significant change in the
      electroluminescence spectrum. This enhancement is attributed to the improved
      light extraction, which is due to the suppression of total internal reflection at
      the interface between the glass substrate and the air.

PMID- 25958536
TI  - Electrochemical and sputtering deposition of hydroxyapatite film on nanotubular
      Ti-25Ta-xZr alloys.
AB  - The purpose of this study was to investigate the electrochemical and sputtering
      deposition of hydroxyapatite film on nanotubular Ti-25Ta-xZr alloys. The
      formation of nanotubular structures was achieved on the alloys by anodization in
      1 M H3PO4 electrolyte containing 0.8 wt% NaF at room temperature. Electrochemical
      deposition was carried out using cyclic voltammetry at 80 degrees C in 5 mM
      Ca(NO3)2+3 mM NH4H2PO4 solution. Then, physical vapor deposition coating was
      obtained by radio frequency magnetron sputtering technique. The microstructures,
      phase transformation, and morphology of the hydroxyapatite film deposited on Ti
      25Ta-xZr alloys were analyzed by optical microscopy, X-ray diffraction, and field
      emission scanning electron microscope. It was found that, as Zr content
      increased, precipitates of hydroxyapatite changed their leaf-like shape into a
      needle-like shape. For the alloy with the higher Zr content, the surface of the
      nanotubes was entirely covered with the radio frequency sputtered HA film.
      Wettability increased in the following order: bulk, nanotubular surface, and
      hydroxyapatite-coated nanotubular surface.

PMID- 25958539
TI  - Antibacterial releasing titanium surface using albumin nanoparticle carriers.
AB  - We developed a simple and highly efficient method for delivery from titanium (Ti)
      surfaces using albumin nanoparticle carriers. A Ti disc with a resorbable
      blasting media surface was used as a metal implant with a localized drug delivery
      structure. Human serum albumin (HSA) nanoparticles loaded with chlorhexidine
      (CHX) diacetate salt hydrate as the model drug were fabricated using a
      desolvation technique. The CHX-loaded HSA nanoparticles produced were cross
      linked with glutaraldehyde (GA). The nanoparticles were pre-coated with
      positively-charged polyethylenimine (PEI) molecules and then immobilized via
      electrical interactions on the negatively charged Ti disc surface. Our results
      suggested that the PEI-coated HSA nanoparticles loaded with CHX (PEI-CHX-HSA)
      were incorporated successfully and well-dispersed on the Ti disc surfaces. The
      agar diffusion test on the Ti surface treated with PEI-CHX-HSA nanoparticles
      showed a larger growth inhibition zone of Streptococcus mutans versus the control
      Ti surface, suggesting that this innovative delivery platform imparts potent
      antibacterial activity to the Ti surface. Thus, CHX, which inhibits the growth of
      oral bacteria, can be efficiently incorporated onto Ti surfaces by using HSA
      nanoparticles.

PMID- 25958538
TI  - Nanoscale poly(4-hydroxybutyrate)-mPEG carriers for anticancer drugs delivery.
AB  - Despite several advancements in chemotherapy, cancer is still the second most
      frequent cause of mortality worldwide. Drug delivery to solid tumors is one of
      the most challenging aspects in cancer therapy. In pharmaceutical industries
      biodegradable polymeric nanoparticles as drug carriers have attracted great
      research interest because of their biocompatibility, biodegradability and
      sustained release of drugs. In our study we prepared poly(4-hydroxybutyrate)-mPEG
      (P(4HB)-mPEG) nanocarriers for the delivery of cisplatin as anticancer drug to
      mouse hippocampal HT22 cells. P(4HB) is more suitable candidate to be utilized in
      pharmaceutical industries due to its wide medical applications. P(4HB) is a
      homopolymer of 4-hydroxybutyrate (4HB), and belongs to a diverse class of
      materials called polyhydroxyalkanoates (PHA) produced by microorganisms inside
      the cells as energy storage materials. P(4HB) has certain unique properties such
      as biocompatibility and rapid in vivo degradation, which differentiate it from
      others PHA based polymers. Novel amorphous amphiphilic block copolymer P(4HB)
      mPEG nanocarriers were prepared and characterized. Flow cytometry, and confocal
      microscopy revealed a suppression effect by the cisplatin loaded nanocarriers on
      HT22 cell growth, and enhancement of apoptotic process of the cells compared to
      free drug treated cells. The amorphous polymeric nanocarriers could be effective
      vehicles for the sustained delivery of toxic anticancer drugs for the therapy of
      cancer.

PMID- 25958540
TI  - Biocompatibility of nanotube formed Ti-30Nb-7Ta alloys.
AB  - The purpose of this study was to investigate the biocompatibility of Ti-30Nb-7Ta
      alloy surface decorated with TiO2 nanotubes by anodization in an electrolyte
      containing 1 M H3PO4 and 0.8 wt.% NaF with an applied voltage of 10 V for 2 h.
      The anodization was carried out using a scanning potentiostat. The
      microstructures of alloys and morphology of the nanotubes were investigated by
      optical microscopy, field emission scanning electron microscopy, and X-ray
      diffractometry. In comparison to the Ti-30Nb-3Ta alloy, the Ti-30Nb-7Ta alloy
      contained a lower amount of alpha" phase, while the beta phase was higher. In
      this study, we observed the formation of a spongy porous layer on the Ti-30Nb-7Ta
      alloy, while the Ti-30Nb and Ti-30Nb-3Ta alloys showed an absence of such a
      spongy layer.

PMID- 25958541
TI  - Enzyme-free glucose sensor based on Au nanobouquet fabricated indium tin oxide
      electrode.
AB  - In this study, we demonstrated a simple, rapid and inexpensive fabrication method
      to develop a novel gold nanobouquet structure fabricated indium tin oxide
      (GNB/ITO) electrode based on electrochemical deposition of gold ions onto ITO
      substrate. The morphology of the fabricated electrode surface was characterized
      by scanning electron microscopy (SEM) to confirm the GNB formation. Enzyme-free
      detection of glucose using a GNB/ITO electrode was described with high
      sensitivity and selectivity based on cyclic voltammetry assay. The results
      demonstrate a linear relation within wide concentration range (500 nM to 10 mM)
      of glucose, with a correlation coefficient of 0.988. The interference effect of
      uric acid was effectively avoided for the detection of glucose (1 MUM to 10 mM).
      Moreover, the developed sensor was applied to determine the concentration of
      glucose in the presence of human serum to indicate the ability of GNB/ITO
      electrodes in real samples. Hence, newly developed GNB/ITO electrode has
      potential application in enzyme-free glucose sensor with highly sensitivity and
      selectivity.

PMID- 25958542
TI  - Microporous Ti implant compact coated with hydroxyapatite produced by electro
      discharge-sintering and electrostatic-spray-deposition.
AB  - A single pulse of 1.5 kJ/0.7 g of atomized spherical Ti powder from 300 MUF
      capacitor was applied to produce the porous-surfaced Ti implant compact by
      electro-discharge-sintering (EDS). A solid core surrounded by porous layer was
      self-consolidated by a discharge in the middle of the compact in 122 MUsec.
      Average pore size, porosity, and compressive yield strength of EDS Ti compact
      were estimated to be about 68.2 MUm, 25.5%, and 266.4 MPa, respectively. Coatings
      with hydroxyapatite (HAp) on the Ti compact were conducted by electrostatic-spray
      deposition (ESD) method. As-deposited HAp coating was in the form of porous
      structure and consisted of HAp particles which were uniformly distributed on the
      Ti porous structure. By heat-treatment at 700 degrees C, HAp particles were
      agglomerated each other and melted to form a highly smooth and homogeneous HAp
      thin film consisted of equiaxed nano-scaled grains. Porous-surfaced Ti implant
      compacts coated with highly crystalline apatite phase were successfully obtained
      by using the EDS and ESD techniques.

PMID- 25958543
TI  - Measurement of band offsets in Y2O3/InGaZnO4 heterojunctions.
AB  - The valence band discontinuity (DeltaE(v)) of Y2O3/InGaZnO4 (IGZO)
      heterojunctions was measured by a core-level photoemission method. The Y2O3
      exhibited a band gap of -6.27 eV from absorption measurements. A value of
      DeltaE(v) = 0.44 +/- 0.21 eV was obtained by using the Ga 2p3/2, Zn 2p3/2 and in
      3d5/2 energy levels as references. Given the experimental bandgap of 3.2 eV for
      the IGZO, this would indicate a conduction band offset DeltaE(c) of - 2.63 eV in
      the Y2O3/IGZO heterostructures and a nested interface band alignment.

PMID- 25958544
TI  - White organic light-emitting diodes with single active layer using a solution
      process based on a co-host emitter system.
AB  - A two-color white organic light-emitting diode (WOLED) with a co-host system in
      solution process method was demonstrated. The device configuration was
      ITO/PEDOT:PSS (40 nm)/emitting layer (50 nm)/TPBi (20 nm)/LiF (1 nm)/Al. The
      emitting layer consisted of TAT, (alpha- or beta-) NPB, DPAVBi (blue dopant), and
      Rubrene (yellow dopant). The device using alpha-NPB or beta-NPB showed a white
      color of CIE (0.29, 0.40) and (0.28, 0.39). The device using the alpha-NPB co
      host showed a luminance efficiency of 3.39 cd/A, which is 21% higher than beta
      NPB (2.80 cd/A). Power efficiency was increased by 16% in alpha-NPB (2.34 Im/W)
      compared to beta-NPB (2.02 Im/W). The Co-host emitter system of HTL and single
      blue emitter using a solution process for WOLED was shown before, but the HTL
      role was not understood clearly. From this study, the WOLED device efficiency can
      be attributed to the HTL's energy transfer property in the emitter mixing system.

PMID- 25958545
TI  - Development of a Smartphone-based reading system for lateral flow immunoassay.
AB  - This study was conducted to develop and evaluate the performance of the
      Smartphone-based reading system for the lateral flow immunoassay (LFIA).
      Smartphone-based reading system consists of a Samsung Galaxy S2 Smartphone,
      Smartphone application, and a LFIA reader. LFIA reader is composed of the close
      up lens with a focal length up to 30 mm, white LED light, lithium polymer
      battery, and main body. The Smartphone application for image acquisition and data
      analysis was developed on the Android platform. The standard curve was obtained
      by plotting the measured P(T)/P(c) or A(T)/A(c) ratio versus Salmonella standard
      concentration. The mean, standard deviation (SD), recovery, and relative standard
      deviation (RSD) were also calculated using additional experimental results. These
      data were compared with that obtained from the benchtop LFIA reader. The LOD in
      both systems was observed with 10(6) CFU/mL. The results show high accuracy and
      good reproducibility with a RSD less than 10% in the range of 10(6) to 10(9)
      CFU/mL. Due to the simple structure, good sensitivity, and high accuracy of the
      Smartphone-based reading system, this system can be substituted for the benchtop
      LFIA reader for point-of-care medical diagnostics.

PMID- 25958546
TI  - Hyaluronic acid/poly(lactic-co-glycolic acid) core/shell fiber meshes loaded with
      epigallocatechin-3-O-gallate as skin tissue engineering scaffolds.
AB  - In this study, hyaluronic acid (HA)/poly(lactic-co-glycolic acid, PLGA)
      core/shell fiber meshes loaded with epigallocatechin-3-O-gallate (EGCG) (HA/PLGA
      E) for application to tissue engineering scaffolds for skin regeneration were
      prepared via coaxial electrospinning. Physicochemical properties of HA/PLGA-E
      core/shell fiber meshes were characterized by SEM, Raman spectroscopy, contact
      angle, EGCG release profiling and in vitro degradation. Biomechanical properties
      of HA/PLGA-E meshes were also investigated by a tensile strength test. SEM images
      showed that HA/PLGA-E fiber meshes had a three-dimensional interconnected pore
      structure with an average fiber diameter of about 1270 nm. Raman spectra revealed
      that EGCG was uniformly dispersed in the PLGA shell of meshes. HA/PLGA-E meshes
      showed sustained EGCG release patterns by controlled diffusion and PLGA
      degradation over 4 weeks. EGCG loading did not adversely affect the tensile
      strength and elastic modulus of HA/PLGA meshes, while increased their
      hydrophilicity and surface energy. Attachment of human dermal fibroblasts on
      HA/PLGA-E meshes was appreciably increased and their proliferation was steadily
      retained during the culture period. These results suggest that HA/PLGA-E
      core/shell fiber meshes can be potentially used as scaffolds supporting skin
      regeneration.

PMID- 25958548
TI  - Effect of alumina nanofiller on properties of heat-treated glass composite
      sealants.
AB  - Alkali/alkaline-earth borosilicate glass-alumina composites containing 10 vol%
      Al2O3 were prepared for use as solid oxide fuel cell sealants. The effect of heat
      treatment and Al2O3, addition on the viscosities and electrical conductivities
      was investigated to improve cyclic sealing performance. Upon a 48-h heat
      treatment, the viscosity of the glass-alumina composites at 750 degrees C was
      approximately four orders of magnitude higher than that of the base glass owing
      to the crystallization of the glass in the presence of Al2O3. Heat treatment
      increased the electrical conductivities of both the base glass and the glass
      alumina composites. The electrical conductivities of glass-alumina composites in
      the range from 400 degrees C to 550 degrees C were three times higher than those
      of the base glass regardless of heat treatment. This increase in the
      conductivities and viscosities by heat treatment was attributed to the
      devitrification and structural densification of the sealing glass and the partial
      dissolution of the Al2O3 filler in alkali/alkaline-earth borosilicate sealing
      glass.

PMID- 25958547
TI  - Bioactivity of cellulose acetate/hydroxyapatite nanoparticle composite fiber by
      an electro-spinning process.
AB  - Hydroxyapatite/cellulose acetate composite webs were fabricated by an electro
      spinning process. This electro-spinning process makes it possible to fabricate
      complex three-dimensional shapes. Nano fibrous web consisting of cellulose
      acetate and hydroxyapatite was produced from their mixture solution by using an
      electro-spinning process under high voltage. The surface of the electro-spun
      fiber was modified by a plasma and alkaline solution in order to increase its
      bioactivity. The structure, morphology and properties of the electro-spun fibers
      were investigated and an in-vitro bioactivity test was evaluated in simulated
      body fluid (SBF). Bioactivity of the electro-spun web was enhanced with the
      filler concentration and surface treatment. The surface changes of electro-spun
      fibers modified by plasma and alkaline solution were investigated by FT-IR
      (Fourier Transform Infrared Spectroscopy) and XPS (X-ray Photoelectron
      Spectroscopy).

PMID- 25958549
TI  - Effect of oxygen plasma treatment on carbon nanotube-based sensors.
AB  - We present the research results of the use of plasma modification for the
      fabrication of carbon nanotube-based devices for chemical and biological sensing.
      The oxygen plasma treatment of multiwalled carbon nanotubes (MWCNTs) effectively
      grafts oxygen atoms onto the CNT surface. For investigating the impact of plasma
      modification on the MWCNT-based sensor performance, three different sensors are
      fabricated: NH3 gas sensors, humidity sensors, and immunosensors. The plasma
      modified MWCNTs (p-MWCNTs) exhibit a sensitivity to NH3 that is approximately
      twice that of the corresponding untreated sensor. The humidity sensor with a p
      MWCNT top electrode exhibits a much faster response time compared with the
      untreated MWCNT electrodes. The p-MWCNT immunosensor exhibits a detection limit
      almost 1000 times lower than that of the standard ELISA assay, while the
      untreated MWCNTs exhibit no detectable signal. These results imply that the
      oxygen-containing functional groups on the CNT surface significantly affect the
      performance of the CNT-based chemical and biological sensors.

PMID- 25958550
TI  - Influence of Sn doping on structural and optical properties of zinc oxide
      nanorods prepared via hydrothermal process.
AB  - Hydrothermally grown ZnO nanorods were doped with various concentrations of Sn,
      ranging from 0 to 2.5 at%. Scanning electron microscopy (SEM), X-ray
      diffractometer (XRD), ultraviolet (UV)-visible spectroscopy, and
      Photoluminescence (PL) measurements were used to determine the effect of Sn
      doping on the structural and optical properties. In the SEM images, the nanorods
      have hexagonal wurtzite structure and the diameter of the nanorods increases with
      an increase in the Sn content. The optical parameters of the Sn-doped ZnO (SZO)
      nanorods such as the absorption coefficients, optical bandgaps, Urbach energies,
      refractive indices, dispersion parameters, dielectric constants, and optical
      conductivities were determined from the transmittance and reflectance results. In
      the PL spectra, the intensity of the NBE peak in the UV region decreases and is
      blue-shifted with an increase in the Sn content, while the DLE peaks of the
      nanorods in the visible region shift toward the low-energy region with the
      introduction of Sn.

PMID- 25958551
TI  - Catalytic co-pyrolysis of waste particle board and polyproplylene over nanoporous
      Al-MCM-41 catalysts.
AB  - Catalytic co-pyrolysis of particle board, a waste wood biomass, and polypropylene
      (PP), a petroleum-based plastic, was carried out with a mixing ratio of 1:1 over
      a representative mesoporous material, Al-MCM-41 catalyst. The Si/Al ratios of the
      Al-MCM-41 catalysts were controlled at 20 and 80 to investigate the effect of the
      acidity of the catalyst. The characterization of the catalyst was performed by X
      ray diffraction, N2 adsorption-desorption, and NH3 temperature-programmed
      desorption. The catalytic pyrolysis of the particle board showed a higher yield
      of gas and lower yield of oil than the non-catalytic pyrolysis. In oil, the
      concentration of levoglucosan decreased, and those of furans, furanones,
      cyclopentanones, aromatics, and light phenolics increased. In the case of the co
      pyrolysis of the particle board and PP, C10-C17 products corresponding to the
      diesel range greatly increased and resulted in an improvement of the bio-oil
      quality. This suggests that PP is decomposed on the acidic sites of the Al-MCM-41
      catalyst, resulting in an increased production of hydrocarbons in the range of
      diesel.

PMID- 25958552
TI  - Fabrication and characterization of SnO2/ZnO gas sensors for detecting toluene
      gas.
AB  - This study investigates the use of SnO2, ZnO, Ag, Au, Cu, In, Pd, Ru and carbon
      black to improve the sensitivity of a gas sensor for detecting toluene gas. Metal
      SnO2/ZnO thick films were screen-printed onto Al2O3 substrates with platinum
      electrodes. The physico-chemical properties of the sensor materials were
      characterized using SEM/EDS, XRD, and BET analyses. Measuring the electrical
      resistance of each sensor as a function of the gas concentration determined the
      sensing characteristics. The sensors were tested using toluene, benzene, xylene,
      ethanol, methanol, ammonia and trimethylamine vapors with concentrations of 1
      2000 ppm. The gas sensing properties of metal-SnO2/ZnO thick films depended on
      the content and variety of metals and the content of carbon black. The optimum
      condition of sensor material for toluene gas detection is operation temperature
      300 degrees C and when metal catalyst Cu and carbon black were added. The best
      sensitivity and selectivity for toluene gas at 300 degrees C resulted from doping
      with 5 wt.% carbon black, 1 wt.% Cu and 20 wt.% ZnO to SnO2.

PMID- 25958553
TI  - Synthesis of PbMoO4 nanoparticles by microwave-assisted hydrothermal process and
      their photocatalytic activity.
AB  - Lead molybdate (PbMoO4) was successfully synthesized using a microwave-assisted
      method and characterized by XRD, Raman spectroscopy, SEM, PL and DRS. We also
      investigated the photocatalytic activity of these materials for the decomposition
      of Rhodamin B under UV-light irradiation. The XRD and Raman results revealed the
      successful synthesis of 42-52 nm, well-crystallized PbMoO4 crystals with the
      microwave-assisted hydrothermal method. The PbMoO4 catalysts prepared using the
      microwave-assisted process enhanced the photocatalytic activity compared to that
      prepared by hydrothermal method and the catalysts prepared at a solution pH = 11
      and temperature of 105 degrees C showed the highest photocatalytic activity. The
      PL peaks appeared at about 540 nm for all catalysts and the excitonic PL signal
      was proportional to the photocatalytic activity for the decomposition of Rhodamin
      B.

PMID- 25958554
TI  - Catalytic combustion of benzene over CuO-CeO2 mixed oxides.
AB  - Catalytic combustion of benzene over CuO-CeO2 mixed oxides has been investigated.
      The CuO-CeO2 mixed oxides were prepared by the combustion method using malic acid
      as an organic fuel and characterized by XRD, XPS and TPR. For the CuO-CeO2
      catalyst with a Cu/(Cu + Ce) molar ratio of more than 0.4, highly dispersed
      copper oxide species were shown at 2theta = 35.5 degrees and 38.8 degrees. The
      CuO-CeO2 catalyst prepared using 2.0 M malic acid showed the highest activity,
      with conversion reaching nearly 100% at 350 degrees C. In addition, the highest
      activity is shown on Cu0.40 (the index denotes the molar ratio Cu/(Cu + Ce))
      sample and then it decreases on Cu0.5 and Cu0.7 samples.

PMID- 25958555
TI  - Optical parameters of boron-doped ZnO nanorods grown by low-temperature
      hydrothermal reaction.
AB  - Sol-gel spin-coating was used to deposit ZnO seed layers onto quartz substrates,
      and ZnO nanorods doped with various concentrations of B (i.e., BZO nanorods)
      ranging from 0 to 2.0 at% were hydrothermally grown on the ZnO seed layers. The
      effects of B doping on the absorption coefficient, optical band gap, Urbach
      energy, refractive index, extinction coefficient, single-oscillator energy,
      dispersion energy, average oscillator strength, average oscillator wavelength,
      dielectric constant, and optical conductivity of the hydrothermally grown BZO
      nanorods were investigated. The optical band gaps were 3.255, 3.243, 3.254,
      3.258, and 3.228 eV for the nanorods grwon at 0, 0.5, 1.0, 1.5 and 2.0 at% B,
      respectively. B doping increased the Urbach energy from 40.7 to 65.1 meV for the
      nanorods grown at 0 and 2.0 at% B, respectively, and significantly affected the
      dispersion energy, the single-oscillator energy, the average oscillator
      wavelength, the average oscillator strength, the refractive index, and the
      optical conductivity of the hydrothermally grown BZO nanorods.

PMID- 25958556
TI  - Efficient exfoliation of MoS2 with volatile solvents and their application for
      humidity sensor. .
AB  - Liquid-phase exfoliation is likely to be feasible for practical fabrication of
      few-layer MoS2 nanosheets in large quantities. However, this method generally
      involves the organic solvents with high boiling point; new strategy using low
      boiling-point solvents to obtain high MoS2 concentration is still highly
      required. In this study, using the strategy of Hansen solubility parameters
      (HSP), a method based on exfoliation of MoS2 in chloroform/acetonitrile mixtures
      is demonstrated to fabricate high concentration MoS2 nanosheet solution. The
      highest concentration of few-layer MoS2 nanosheets and nanoparticles up to 0.4
      mg/ml is achieved with the optimum composition of mixture. The MoS2 nanosheet
      thin film is also investigated in terms of their sensing properties towards
      humidity. The exfoliated MoS2 based thin film sensor exhibited excellent
      sensitivity, quick response and recovery, and good reproducibility comparing to
      their bulk counterpart. The excellent sensing performance of exfoliated MoS2 is
      generally attributed to the high surface-to-volume-ratio and increased ratio of
      edge sites and basal plane sites after exfoliation.

PMID- 25958558
TI  - High temperature carbon dioxide capture on nano-structured MgO-Al2O3 and CaO
      Al2O3 adsorbents: an experimental and theoretical study.
AB  - Nano-structured alkaline-earth metal oxide adsorbents (denoted as MgO-Al2O3 and
      CaO-Al2O3) were prepared by an epoxide-driven one-pot sol-gel method, and they
      were applied to the dynamic and static CO2 adsorption. For comparison, a nano
      structured aluminum oxide adsorbent (denoted as Al2O3) was also prepared by a
      similar method. MgO-Al2O3 adsorbent exhibited a well-developed mesopore structure
      through the formation of MgAl2O4 spinel phase, whereas CaO-Al2O3 adsorbent was
      composed of nano-sized CaO and CaAl2O4, resulting in a pore plugging. It was
      revealed that total basicity increased in the order of Al2O3 (0.11 mmol-CO2/g) <
      MgO-Al2O3 (0.37 mmol-CO2/g) < CaO-Al2O3, (1.21 mmol-CO2/g), which is in
      concurrent with adsorption energy obtained from DFT calculations. However, it was
      found that both basicity and base strength of the adsorbents played an important
      role in determining the CO2 adsorptive performance at different operating
      temperature. Among the adsorbents tested, MgO-Al2O3, which mostly retained medium
      basic sites, exhibited a best CO2 adsorptive performance at 200 degrees C.
      Furthermore, the experimental results are well supported by theoretical
      estimation, suggesting a useful design method of adsorbents for facile and
      regenerative adsorption in the applications of CO2 capture.

PMID- 25958557
TI  - High functional nano materials for ophthalmic lenses containing silicon 2,3
      naphthalocyanine bis(trihexylsilyloxide) and silicon 2,9,16,23-tetra-tert-butyl
      29H31 H-phthalocyanine dihydroxide.
AB  - High functional ophthalmic lens materials, poly(HEMA-co-GMA)s were prepared by
      the copolymerization of HEMA, MMA, NVP, EDGMA and GMA in the presence of SiNc
      [silicon 2,3-naphthalocyanine bis(trihexylsilyloxide)] and SiPc (silicon
      2,9,16,23-tetra-tert-butyl-29H31H-phthalocyanine dihydroxyde). Also, the physical
      and optical characteristics of the produced polymers were analyzed to investigate
      UV-blocking capabilities of these functional ophthalmic dyes and their
      applicability as materials for colored hydrogel contact lenses. For G_SN samples
      to which GMA was added to the Ref._SN combination, the transmittance for visible
      ray, UV-B and UV-A was in the range of 86.0-89.4%, 63.0-67.6% and 62.5-66.0%
      respectively. Also, for G_SP samples, the transmittance for visible ray, UV-B and
      UV-A was in the range of 85.2-87.0%, 70.0-72.6 and 68.0-70.2% respectively. The
      measurement of the spectral transmittance showed that both SiNc and SiPc absorbed
      a small amount of UV light, but the absorption pattern for UV light differed for
      each material. Based on the results, the addition of SiNc and SiPc to ophthalmic
      polymer materials can be used for various purposes in colored ophthalmic lens
      that are capable of offering protection from UV and infrared light without
      significant change of the physical properties.

PMID- 25958559
TI  - Preparation and characterization of thin silicate-coated fluorescent silica
      nanoparticles with enhanced stability.
AB  - Silica nanoparticles (SNPs) were functionalized by aminosilanes of different
      chain lengths, such as (3-aminopropyl) trimethoxysilane (APTMS), [3-(2
      aminoethylamino)propyl] trimethoxysilane (AEAPTMS), and N-(3
      trimethoxysilylpropyl)diethylenetriamine (TMSP), followed by the electrostatic
      conjugation with carboxyl quantum dots (QDs). The resulting QD-anchored SNPs (Q
      SNPs) were treated with a silicate solution to afford thin silica-coated
      fluorescent nanoparticles. The Q-SNPs prepared using AEAPTMS exhibited the
      highest photoluminescence (PL) intensity compared to those prepared using APTMS
      and TMSP. Moreover, the conjugation of amine-terminated SNPs with carboxyl QDs
      was found to be very strong under acidic pH conditions. The silicate-coated Q
      SNPs exhibited a long-lasting PL intensity compared to the pristine Q-SNPs
      because the silica coating prevented the oxidative degradation and/or detachment
      of the anchored QDs from the SNPs. Such a protective coating strategy would be a
      useful guideline to prepare stable nanostructured materials for prolonged
      applications. The composite particles were characterized by scanning electron
      microscopy (SEM), transmission electron microscopy (TEM), dynamic light
      scattering (DLS), and photoluminescence (PL) spectroscopy.

PMID- 25958560
TI  - Effect of Co doping concentration on structural properties and optical parameters
      of Co-doped ZnO thin films by sol-gel dip-coating method.
AB  - The structural and optical properties of Co-doped ZnO thin films prepared by a
      sol-gel dip-coating method were investigated. X-ray diffraction analysis showed
      that the thin films were grown with a c-axis preferred orientation. The position
      of the (002) peak was almost the same in all samples, irrespective of the Co
      concentration. It is thus clear that Co doping had little effect on the position
      of the (002) peak. To confirm that Co2+ was substituted for Zn2+ in the wurtzite
      structure, optical measurements were conducted at room temperature by a UV
      visible spectrometer. Three absorption peaks are apparent in the Co-doped ZnO
      thin films that do not appear for the undoped ZnO thin film. As the Co
      concentration was increased, absorption related to characteristic Co2+
      transitions increased because three absorption band intensities and the area
      underneath the absorption wells between 500 and 700 nm increased with increasing
      Co concentration. The optical band gap and static dielectric constant decreased
      and the Urbach energy and extinction coefficient increased with increasing Co
      concentration.

PMID- 25958561
TI  - Tunable assembly of hydrophobic and cationic charged Fe3O4/SiO2 colloids.
AB  - The hydrophobic and cationic Fe3O4/SiO2 nanoparticles (NPs) were synthesized by
      coating the Fe3O4 nanoparticles with silica followed by the silanization
      reaction. The monodisperse nanoparticles were separated under magnetic forces and
      characterized by FE-SEM and FT-IR. Interestingly, the hydrophobic and cationic
      NPs were well dispersed in polar solvents (ethanol and propylene carbonate) and a
      nonpolar solvent (chloroform). The structural colors induced by the assembly of
      the NPs were changed according to the magnetic forces. The repulsive forces
      originated from the combination of the cationic charges and hydrophobic groups
      were strong enough to overcome the magnetic attractive forces between particles.
      The electrophoretic behavior of the NPs was investigated as well. For preparing
      devices, the polar and nonpolar solutions of the cationic NPs were injected into
      the cells with two ITO-coated glasses which were separated by 100 MUm. The
      reversible color changes were observed on the cathode under the electric field
      suggesting that the Fe3O4/SiO2 nanoparticles were modified with cationic groups.

PMID- 25958562
TI  - Effects of sintering temperature on the pyrochlore phase in PZT nanotubes and
      their transformation to the perovskite phase by coating with PbO multilayers.
AB  - We report the phase evolution of Pb(Zr0.52Ti0.48)O3 nanotubes (PZT-NTs), from the
      pyrochlore to perovskite phase, with an outer diameter of about 420 nm and a wall
      thickness of about 10 nm. The PZT-NTs were fabricated in pores of porous anodic
      alumina membrane (PAM) using a spin coating of PZT sol-gel solution and
      subsequent annealing at 500-700 degrees C in oxygen gas. The pyrochlore phase was
      found to be formed at 500 degrees C, and also found not to be transformed into
      the perovskite phase, even though annealing was performed at higher temperatures
      to 700 degrees C. Elementary distribution analysis of PZT-NTs embedded in PAM
      reveal that Pb diffusion from nanotubes into pore walls of PAM is one of the main
      reasons. By employing firstly an additional PbO coating on the pyrochlore
      nanotubes and then subsequent annealing at 700 degrees C, we have successfully
      achieved an almost pure perovskite phase in nanotubes. These results suggest that
      PbO acts as a Pb-compensation agent in the Pb- deficient PZT-NTs. Moreover, our
      method can be used in the synthesis of all metal-oxide materials, including
      volatile elements.

PMID- 25958563
TI  - Performance enhancement in inverted solar cells by interfacial modification of
      ZnO nanoparticle buffer layer.
AB  - Polymer solar cells (PSCs) have attracted increasing attention in recent years.
      The rapid progress and mounting interest suggest the feasibility of PSC
      commercialization. However, critical issues such as stability and the weak nature
      of their interfaces posses quite a challenge. In the context of improving
      stability, PSCs with inverted geometry consising of inorganic oxide layer acting
      as an n-buffer offer quite the panacea. Zinc oxide (ZnO) is one of the most
      preferred semiconducting wide band gap oxides as an efficient cathode layer that
      effectively extracts and transports photoelectrons from the acceptor to the
      conducting indium-doped tin oxide (ITO) due to its high conductivity and
      transparency. However, the existence of a back charge transfer from metal oxides
      to electron-donating conjugated polymer and poor contact with the bulk
      heterojunction (BHJ) active layer results in serious interfacial recombination
      and leads to relatively low photovoltaic performance. One approach to improving
      the performance and charge selectivity of these types of inverted devices
      consists of modifying the interface between the inorganic metal oxide (e.g., ZnO)
      and organic active layer using a sub-monolayer of interfacial materials (e.g.,
      functional dyes). In this work, we demonstrate that the photovoltaic parameters
      of inverted solar cells comprising a thin overlayer of functional dyes over ZnO
      nanoparticle as an n-buffer layer are highly influenced by the anchoring groups
      they possess. While an inverted PSC containing an n-buffer of only ZnO exhibited
      an overall power conversion efficiency (PCE) of 2.87%, the devices with an
      interlayer of dyes containing functional cyano-carboxylic, cyano-cyano, and
      carboxylic groups exhibited PCE of 3.52%, 3.39%, and 3.21%, respectively, due to
      increased forward charge collection resulting from enhanced electronic coupling
      between the ZnO and BHJ active layers.

PMID- 25958564
TI  - Enhancement of the crystalline Ge film growth by inductively coupled plasma
      assisted pulsed DC sputtering.
AB  - The effect of pulsed DC sputtering on the crystalline growth of Ge thin film was
      investigated. Ge thin films were deposited on the glass substrates using ICP
      assisted pulsed DC sputtering. The Ge target was sputtered using asymmetric
      bipolar pulsed DC sputtering system with and without assistance of ICP source.
      The pulse frequency of 200 Hz and the pulse on time of 500 MUsec (duty cycle =
      10%) were kept during sputtering process. Crystal structures were studied from X
      ray diffraction. The X-ray diffraction patterns clearly showed crystalline film
      structures. The Ge thin films with randomly oriented crystalline were obtained
      using pulsed DC sputtering without ICP, whereas they had well aligned (220)
      orientation crystalline using ICP source. Moreover, the combination of ICP
      assistance and pulsed DC sputtering enhanced the growth of crystalline Ge thin
      films without hydrogen and metal by in situ deposition. The structure and lattice
      of the films were studied from TEM images. The cross-sectional TEM images
      revealed the deposited Ge films with columnar structure.

PMID- 25958565
TI  - Nano-eutectic growth in Co-17.8 wt%Gd alloy ribbons and the magnetostrictive
      properties at different wheel speeds.
AB  - Under near-equilibrium solidification conditions, the Co-17.8 wt%Gd eutectic
      alloy forms rod-like eutectic microstructure of (alphaCo) solid solution and
      Co17Gd2 compound. When the solidification condition is far from the equilibrium,
      the rapid growth of nano-eutectic in Co-17.8 wt%Gd alloy ribbons is realized by
      the single-roller techniques. The average granular size (d) of nano-eutectic in
      the center of ribbons varies with the increase of wheel speed (V), d = 510.36
      25.51 V+0.44 V2. XRD results of ribbons at different wheel speeds indicate that,
      with the rise of wheel speed, the main peak of Co17Gd2 compound becomes more and
      more notable, whereas the main peak of (alphaCo) solid solution tends to reduce.
      Along the length direction, the Co-17.8 wt%Gd alloy ribbons have the negative
      magnetostrictive strain. The magnetostrictive strain enhances with the increase
      of wheel speed. At the wheel speed of 40 m/s, the magnetostrictive coefficient of
      ribbons is measured to be - 733 ppm at the magnetic field of 6 kOe. The influence
      of the wheel speed and the magnetic field on the maanetostrictive coefficient is
      discussed.

PMID- 25958566
TI  - Pb(II) ion-imprinted micro-porous particles for the selective separation of
      Pb(II) ions.
AB  - Pb(II) ion-imprinted micro-porous particles were prepared from the ionic
      complexes formed between vinyl pyridine functional monomers and template Pb(II)
      ions. The self-assembled Pb(II)/monomer complex was suspension polymerized in the
      presence of divinylbenzene cross-linker. The prepared micro-particles were 400
      600 MUm in size. Their chemical and physical structures, morphologies, and
      adsorption capacity were analyzed by energy dispersive X-ray spectrometry (EDX)
      Brunauer-Emmett-Teller (BET) analysis, scanningelectron microscopy (SEM), and
      atomic adsorption spectroscopy (AAS). The adsorption capacity of the imprinted
      polymer for the Pb(II) template ions was significantly affected by the initial
      concentration and the pH of the feed solution. Adsorptionis rapid in the first 1
      h, after which it slowly increases to equilibrium. The imprinted particles showed
      high selectivity for lead ions; the adsorption capacity for the Pb(II) ions, 28
      mg g(-1) polymer, was much higher than those for other metal ions such as
      Ni(II)Zn(II), Fe(II), or Cd(II). The imprinted particles maintain high standards
      of their adsorption ability after 10 repeated uses.

PMID- 25958567
TI  - Effect of concentration on the growth of rutile TiO2 nanocrystals.
AB  - In the following study we present an easy and scalable method for the synthesis
      of Rutile Titanium Dioxide (TiO2) nano-rods by using bulk TiO2 powder, Sodium
      Hydroxide (NaOH), distilled water and ethanol. We demonstrated the effects of
      concentration on the size, morphology and band gap of the finally obtained
      nanostructures. X-ray diffraction pattern (XRD) studies indicated that the
      samples were crystalline and were free from any impurities with a little hint of
      anatase at the lower concentrations and the average crystal size ranges between
      20 nm to 41 nm, FESEM studies revealed that nano structures are rod like. Further
      UV-Visible Spectroscopy and Raman studies were conducted of the prepared samples
      and the band gap of the samples was found to be ranging from 3.5 eV to 3.8 eV.
      The photo-catalytic degradation of methyl orange was done by the sample prepared
      in the presence of UV source and was compared with the degrading capacity of bulk
      TiO2 and was inferred that the Methyl orange is degraded much efficiently with
      the use of the synthesized sample. The central feature of the presented approach
      being the use of simple technique and instruments like hot plate, economical and
      easily accessible chemical like NaOH as a reactant, and a facilitator for the
      growth of nano-rods and with the reaction being carried out at very low
      temperatures and less reaction times makes this technique highly feasible for
      being used in mass production of Rutile TiO2 nano-rods and the fact that the
      morphology and size can be tuned by varying the concentration of the NaOH.

PMID- 25958568
TI  - Doping dependent properties of Cr-doped ZnO nanostructures prepared by microwave
      irradiation.
AB  - In this work, undoped and Cr-doped single-crystalline ZnO nanorods were prepared
      by a facile microwave assisted solution method. X-ray diffraction (XRD) and
      transmission electron microscopy (TEM) results showed that Cr-doped ZnO was
      comprised of single phase nature with hexagonal wurtzite structure up to 5% Cr
      doping, however, secondary phase ZnCr2O4 appeared upon further increasing the Cr
      dopant concentration. Field emission scanning electron microscopy (FESEM) and TEM
      micrographs suggested that the undoped nanorods with an average length of -~2 MUm
      and a diameter in the range of 150-200 nm, respectively were observed.
      Interestingly, the size of nanorods decreased with the increase of Cr
      concentration in ZnO. Optical studies depicted that the energy bandgap was
      decreased with the increase of Cr concentration. Raman scattering spectra of Cr
      doped ZnO revealed the lower frequency shift of E2(high) phonon mode with the
      increase in concentration of Cr dopant, suggested the successful doping of Cr
      into Zn site in ZnO. Magnetic studies showed that Cr-doped ZnO exhibited room
      temperature ferromagnetism (RTFM) and the value of magnetization was continuously
      decreased with the increase in Cr doping.

PMID- 25958569
TI  - Evaluation of nanocomposite gate insulators for flexible organic thin-film
      transistors.
AB  - To develop physically flexible electronics, high performance and mechanical
      stability of component materials and devices are required. For a flexible
      display, a backplane with flexible thin-film transistors (TFTs) must be
      developed. Gate insulating materials with excellent electrical and mechanical
      properties are highly important to the development of flexible TFTs. We
      investigated nanocomposite gate dielectrics composed of polyimide (PI) because of
      their superior thermal stability, as well as different inorganic HfO2, TiO2, and
      Al2O3 nanoparticles with high dielectric constants. Nanocomposite gate
      dielectrics of HfO2 nanoparticles and PI lowered leakage current density and
      increased the relative dielectric constant compared to PI solely because of a
      high degree of dispersion. Pentacene TFTs with HfO2 nanocomposite gate insulators
      also showed higher field-effect mobility (MU), smaller subthreshold swing, and an
      enhanced on/off current ratio (I(on/off)) compared to those of the PI gate
      dielectric. In addition, mechanical cyclic bending tests involving bending cycles
      of 2 x 10(5) time sat a bending radius of 5 mm showed improvement in electrical
      stability of nanocomposite gate insulators with a change in leakage current
      density of nanocomposite gate insulators below 30%.

PMID- 25958570
TI  - Graphene-containing carbon aerogel prepared using polyethyleneimine (PEl)
      modified graphene oxide (GO) for supercapacitor: effect of polyethyleneimine
      modified GO content.
AB  - Graphene-containing carbon aerogel was prepared by a sol-gel polymerization of
      resorcinol-formaldehyde (RF) method using polyethyleneimine (PEL)-modified
      chemically exfoliated graphene oxide (GO), and its electrochemical performance as
      an electrode for supercapacitor was examined. The effect of PEI-modified GO
      content on the physicochemical and electrochemical properties of graphene
      containing carbon aerogel was investigated. For comparison, graphene-free carbon
      aerogel was also prepared. Among the samples, graphene-containing carbon aerogel
      prepared using 45 wt% PEI-modified GO solution (CA(45PG)) showed the highest BET
      surface area (784 m2/g) and the largest pore volume (1.71 cm3/g) with well
      developed porous structure. Electrochemical properties of graphene-containing
      carbon aerogel and graphene-free carbon aerogel electrodes were measured by
      cyclic voltammetry, charge/discharge test, and electrochemical impedance
      spectroscopy in 6 M KOH electrolyte. Various electrochemical measurements
      revealed that CA(45PG) showed the highest specific capacitance (261 F/g), the
      lowest equivalent series resistance (0.16 Omega), and superior capacitive
      behavior. It is concluded that PEI-modified GO content served as an important
      factor determining the physicochemical properties and supercapacitive
      electrochemical performance of graphene-containing carbon aerogel.

PMID- 25958572
TI  - Reactions of Ni-B on printed Ag pattern by using nearly neutral electroless bath.
AB  - In this study, we investigated the characteristics of a nearly neutral Ni source
      solution including dimethylamine borane (DMAB) used to develop the metal PCB
      (printed circuit board) of high power LED (light-emitting diode) package. In
      accordance with the bath temperature ranging from 50 degrees C to 75 degrees C,
      an electroless Ni-B plating on a screen-printed Ag pattern with an anodized Al
      substrate was carried out. The depositon rate of the electroless plated Ni-B film
      at bath temperature ranging from 50 degrees C to 75 degrees C was estimated by
      measurements of the thickness and the mass. The deposition rates by change of
      thickness and mass of the electroless plated Ni-B film at 50 degrees C were - 58
      nm/min and 0.113 mg/min respectively. The activation energy obtained from slope
      of Arrhenius plot using these deposition rates was - 59 kJ/mol. Finally,
      selectively the film growth was achieved at all plating temperatures, without a
      damage of anodized Al substrate.

PMID- 25958571
TI  - Enhanced switching behavior of iron oxide nanoparticle-doped liquid-crystal
      display.
AB  - It is well known that doping nanoparticles (NPs) in liquid crystals (LCs) can
      easily change the physical and electro-optical properties of LC mixture. In this
      paper, we demonstrate homogeneous, aligned nematic LC (N-LC) system dispersed in
      iron oxide (Fe2O3) NPs. The prepared Fe2O3 NPs have an average particle size of
      50 nm. By changing the doping concentration of Fe2O3 NPs, we observed the
      characteristics of LC systems. Electrooptical (EO) characteristics included
      faster rising and falling times (2.14 ms and 10.24 ms, respectively) and lower
      driving voltage (1.45 V) compared with a pure N-LC cell. We demonstrated these
      results via the relationship between dielectric con- stant and LC device
      properties. The results were verified by software simulation based on general
      physical properties. Moreover, we observed that LC system with Fe2O3 NPs could be
      accomplished without capacitance hysteresis by capturing charged impurities.
      Superior performance of LC cell with Fe2O3 NPs indicates that the proposed LC
      system have strong potential for use in the production of advanced LC displays.

PMID- 25958573
TI  - Electrophoretic deposition of iron catalyst on C-fiber textiles for the growth of
      carbon nanofibers.
AB  - In this study, carbon nanofibers synthesis has been conducted by chemical vapor
      deposition on C-fiber textiles coated with an iron catalyst via electrophoretic
      deposition. C-fiber textiles were oxidized with nitric acid before the iron
      catalyst was plated by electrophoretic deposition. Due to oxidation, the hydroxyl
      group was created on the C-fiber textiles and was used as an active site for iron
      catalyst deposition. It was verified that the iron catalyst was deposited on the
      C-fiber textiles, while current, voltage, and deposition time varied and the
      concentration of electrolyte was kept constant in electrophoretic deposition.
      After being deposited, the iron particles were dried in oven for 24 hours and
      reduced by hydrogen gas in a furnace. Ethylene gas was introduced for the growth
      of carbon nanofibers and the growth temperature was then varied to find the
      optimal growth temperature of the carbon nanofibers. Thus, the characteristics of
      carbon nanofibers were analyzed by Scanning Electron Microscopy (SEM), Energy
      Dispersive Spectroscopy (EDS), N2-sorption (BET), X-Ray Diffraction (XRD), and X
      ray Photoelectron Spectroscopy (XPS). It is verified that the iron particles were
      most evenly deposited at 0.1 A for 3 minutes. Carbon nanofibers grew to 150-200
      nm most evenly at 600 degrees C via temperature variations in CVD.

PMID- 25958574
TI  - Control of silica-zirconia nanoparticles for uniform porous SiO2-ZrO2 membranes.
AB  - Silica-zirconia composite sols were prepared by means of a sol-gel method, using
      tetraethylorthosilicate (TEOS) and zirconium tetra-n-butoxide (ZrTB) precursors.
      TEOS, ZrTB, HCl, H2O and EtOH were mixed at 70 degrees C for 24 hours to give
      molar ratios of 1:1:8-80:0.2-1.0:100-300. The mean particle size of the silica
      zirconia sol was controlled by the concentration of the alkoxides and catalyst,
      as well as the water molar ratio in the starting solution. The particle size of
      the SiO2-ZrO2 sol, which was analyzed by dynamic light scattering (DLS) and field
      emission scanning electron microscopy (FE-SEM), was in the range of 20 to 350 nm.
      The SiO2-ZrO2 sol solutions of different sol sizes were coated onto porous
      stainless steel supports (O.D. 10 mm, length: 20 mm, 316L SUS, Mott corp. USA) by
      a dipping-rolling-freezing-fast drying (DRFF) and soaking-rolling-freezing-fast
      drying (SRFF) method. After coating with SiO2-ZrO2 sol, the single gas permeation
      characteristics (He, H2 and N2) of the resulting SiO2-ZrO2 membranes were
      evaluated at room temperature. This produced a decrease in the mean flow diameter
      and H2/N2 permselectivity in the range of 2.0-3.5. Finally, following the results
      of gas permeation testing, the pore size of the membranes was controlled by
      changing their particle size.

PMID- 25958575
TI  - Effect of laser intensity on the characteristic of inkjet-printed silver
      nanoparticles during continuous laser sintering.
AB  - The variation in electric conductivity was examined for laser irradiation with
      various beam intensities. A 532-nm continuous wave laser was irradiated onto
      inkjet-printed silver lines on a glass substrate and the electrical resistance
      was measured in situ during the irradiation. The results demonstrate that
      electrical conductivity varies nonlinearly with laser intensity, and has a
      minimum specific resistance of 3.1 x 10(-8) Omegam at 4 kW/cm2 irradiation. These
      results are interesting because the specific resistance achieved by the present
      laser irradiation was approximately 1.9 times lower than the best value
      obtainable by oven heating, even though it was still higher by 1.9 times than
      that of bulk silver. It is also demonstrated that the irradiation time required
      to complete the sintering process decreases with laser intensity. The numerical
      simulation of laser heating shows that the heating temperature could be as high
      as 250 degrees C for laser sintering, while it is limited to 250 degrees C for
      oven sintering. The characteristics of sintering with laser intensity based on
      the results of field emission scanning electron microscope images are discussed.

PMID- 25958576
TI  - Semitransparent quantum dot light-emitting diodes by cadmium-free colloidal
      quantum dots.
AB  - The InP/ZnSe/ZnS multishell colloidal quantum dots (QDs) were prepared by
      convenient heating-up method for an emission layer of semitransparent quantum dot
      light-emitting diodes (QD-LEDs). The synthesized InP/ZnSe/ZnS multishell QDs
      exhibited an emission peak at 545 nm for clear green color with a full-width at
      half-maximum (FWHM) of 50 nm, and photoluminescent (PL) quantum yield (QY) of
      45%. The multishell on the indium phosphide (InP) core helped increasing QY and
      stability by reducing interfacial defects. Using a Ca/Ag cathode, the whole QD
      LEDs were semitransparent throughout the visible wavelengths. The maximum
      brightness and currernt efficiency of semitransparent QD-LEDs reached 587 cd/m2
      and 1.52 cd/A by controlling the thickness of Ca/Ag cathode, which is comparable
      to the device with opaque LiF/Al cathode (1444 cd/m2 and 1.98 cd/A). The
      performance of our semitransparent and eco-friendly device is not matched with
      traditional cadmium (Cd) based QD-LEDs yet, but it shows the great potential for
      various window-type information displays.

PMID- 25958577
TI  - Simplified unified model for estimating the motion of magnetic nanoparticles
      within electrohydrodynamic field.
AB  - In previous research, we studied the electrical breakdown characteristics of a
      transformer oil-based magnetic fluid; mailnly, those were carried out by the
      experimental measurements. The first study was aimed at enhancing the dielectric
      breakdown voltage of transformer oil by adding magnetic nanoparticles
      experimentally under the official testing condition of dielectric liquids. The
      next study was focused on explaining the reason why the dielectric
      characterisitics of the fluids were changed through optically visualizing the
      particles motion in a microchannel using an optical microscopic measurement and
      numerically calculating the dielectrophoretic force induced in the fluids with
      considering only the properties of magnetic nanoparticles. In this study, we
      developed a simplified unified model for calculating further the motion of
      magnetic nanoparticles suspended in the presence of electrohydrodynamic field
      using the COMSOL multiphysics finite element simulation suite and investigated
      the effects of magnetic nanoparticle dielectrophoretic activity aimed at
      enhancing the electrical breakdown characteristics of transformer oil.

PMID- 25958579
TI  - Memory effect by carrier trapping into V3Si nanocrystals among SiO2 layers on
      multi-layered graphene layer.
AB  - We report the electrical characteristics and conduction mechanism of a resistive
      switching memory device consisting of V3Si nanocrystals embedded in the SiO2
      layer on multi-layered graphene. The V3Si nanocrystals with average size of 5 nm
      were formed between the SiO2 layers by thin film deposition and post-annealing
      process at 800 degrees C for 5 s. The current values of high (HRS) and low
      resistance states (LRS) at 1 V were measured to be about 3.26 x 10(-9) A and 3.11
      x 10(-8) A, respectively. The ratio of the HRS and LRS after applying sweeping
      bias of +/- 6 V appeared to be about 9.54 at 1 V. The resistance switching could
      originate from the effect of carrier trap and emission into the V3Si nanocrystals
      via the tunneling, space charge limited current, and thermionic emission
      mechanisms controlled by the modulation of the Fermi level of the graphene layer.
      The V3Si nanocrystals memory device has a strong possibility for the application
      of nonvolatile memory devices.

PMID- 25958578
TI  - Preparation of ZnS-graphene nanocomposites under electric furnace and
      photocatalytic degradation of organic dyes.
AB  - Zinc sulfide (ZnS) nanoparticles were synthesized from zinc nitrate hexahydrate
      and thiourea under microwave irradiation. The ZnS-graphene nanocomposites were
      calcined in an electric furnace at 700 degrees C under an inert argon gas
      atmosphere for 2 hr. The heated ZnS-graphene nanocomposites were characterized by
      X-ray diffraction, scanning electron microscopy, transmission electron microscopy
      and UV-vis spectrophotometry. After heat treatment, ZnS-graphene nanocomposites
      had a more porous and larger surface area, than the unheated ZnS-graphene
      nanocomposites. The photocatalytic activity of the heated ZnS-graphene
      nanocomposites in the degradation of organic dyes, such as methylene blue, methyl
      orange, and rhodamine B, under ultraviolet light at 254 nm by UV- vis
      spectrophotometer was evaluated and compared with that of the unheated ZnS
      nanoparticles, heated ZnS nanoparticles, unheated ZnS-graphene nanocomposites.
      Among the our experimental results as a photocatalyst, the heated ZnS-graphene
      nanocomposites exhibited remarkably higher photocatalytic degradation of organic
      dyes as compared to other nanomaterials such as unheated ZnS nanoparticles and
      heated ZnS-graphene nanocomposites.

PMID- 25958580
TI  - Effect of La2O3 addition on interface chemistry between 4YSZ top layer and Ni
      based alloy bond coat in thermal barrier coating by EB PVD.
AB  - The effect of a 5 mol% La2O3 addition on the forming behavior and compositional
      variation at interface between a 4 mol% Yttria (Y2O3) stabilized ZrO2 (4YSZ) top
      coat and bond coat (NiCrAlY) as a thermal barrier coating (TBC) has been
      investigated. Top coats were deposited by electron beam physical vapor deposition
      (EB PVD) onto a super alloy (Ni-Cr-Co-Al) substrate without pre-oxidation of the
      bond coat. Top coats are found to consist of dense columnar grains with a thin
      interdiffusion layer between metallic bond coats. In the as-received 4YSZ
      coating, a thin interdiffusion zone at the interface between the top and bond
      coats was found to consist of a Ni-Zr intermetallic compound with a reduced
      quantity of Y, Al or O elements. On the other hand, in the case of an
      interdiffusion area of 5 mol% La2O3-added 4YSZ coating, it was found that the
      complicated composition and structure with La-added YSZ and Ni-Al rich compounds
      separately. The thermal conductivity of 5 mol% La2O3-added 4YSZ coating (- 1.6
      W/m x k at 1100 degrees C) was lower than a 4YSZ coating (- 3.2 W/m x k at 1100
      degrees C) alone.

PMID- 25958581
TI  - Electrical properties of solution-deposited ZnO thin-film transistors by low
      temperature annealing.
AB  - Flexible oxide thin-film transistors (Oxide-TFTs) have emerged as next generation
      transistors because of their applicability in electronic device. In particular,
      the major driving force behind solution-processed zinc oxide film research is its
      prospective use in printing for electronics. A low-temperature process to improve
      the performance of solution-processed n-channel ZnO thin-film transistors (TFTs)
      fabricated via spin-coating and inkjet-printing is introduced here. ZnO
      nanoparticles were synthesized using a facile sonochemical method that was
      slightly modified based on a previously reported method. The influence of the
      annealing atmosphere on both nanoparticle-based TFT devices fabricated via spin
      coating and those created via inkjet printing was investigated. For the inkjet
      printed TFTs, the characteristics were improved significantly at an annealing
      temperature of 150 degrees C. The field effect mobility, V(th), and the on/off
      current ratios were 3.03 cm2/Vs, -3.3 V, and 10(4), respectively. These results
      indicate that annealing at 150 degrees C 1 h is sufficient to obtain a mobility
      (MU(sat)) as high as 3.03 cm2/Vs. Also, the active layer of the solution-based
      ZnO nanoparticles allowed the production of high-performance TFTs for low-cost,
      large-area electronics and flexible devices.

PMID- 25958582
TI  - Synthesis and properties of hydroxyl-terminated polybutadiene-based polyurethanes
      reinforced with polyhedral oligomeric silsesquioxanes.
AB  - Polyurethane/polyhedral oligomeric silsesquioxane (PU/POSS) hybrid composites are
      prepared by a one-step PU reaction using hydroxyl-terminated polybutadiene (HTPB)
      prepolymer, isophorone diisocyanate (IPDI) and either non-reactive or reactive
      POSS molecule. The effect of incorporation of functionalized POSS molecules
      covalently bonded or physically blended into PU matrix is investigated in terms
      of mechanical reinforcement and thermal stability of these resulting PU/POSS
      hybrid composites. PU/POSS hybrid composites prepared with reactive POSS
      molecules exhibit the mechanical reinforcement while maintaining low glass
      transition temperataure (T(g)), probably due to the fact that reactive POSS
      molecules chemically incorporated in PU are aggregated to crystallize,
      effectively working as a physical crosslinking in PU/POSS hybrid composites. This
      can be advantageous in that mechanical reinforcement of PU/POSS hybrid composites
      can be achived without sacrificing the low temperature properties of these
      composites. However, the contribution of POSS molecules incorporated covalently
      into PU matrix is virtually absent on the thermal decomposition temperature
      (T(d,max)) measured using TGA/DTG. Thermal degradation behavior of these hybrid
      composites in the early stage rather appears to depend preferably on
      characteristics of POSS molecules incorporated.

PMID- 25958583
TI  - Synthesis of photolabile fluorescent polymeric micelles.
AB  - A new amphiphilic block copolymers were synthesized with the atom transfer
      radical polymerization (ATRP) method. Then, the micelle structures were
      fabricated with a self-assembly method for application in nanocarriers and
      sensing. The fluorescent intensity was increased by a factor of 4 in the micelle
      solution due to more stacked pyrene moieties. The core-shell structure of the
      micelle was confirmed by HR-TEM images. The pyrene moieties were positioned in
      the core of the micelle, and the surface consisted of hydrophilic PMMA blocks.
      The ester bond of the polymer backbone was breakable by irradiation with UV
      light. Therefore, the micelle structure was deformed after UV irradiation, and
      the excimer peak was drastically reduced as the monomer peak appeared. The
      deformation of micelle structures was clearly confirmed by FE-SEM and NMR
      analysis. These photolabile polymeric micelles may be widely useful for photo
      stimulative nanocarriers as well as for the design of new functional micelles
      with many other chromophores.

PMID- 25958584
TI  - Corrosion of Ti3SiC2 carbides in N2/H2O/H2S gases at 800 and 900 degrees C.
AB  - The corrosion behavior of Ti3SiC2 carbides was studied at 800 and 900 degrees C
      for 30 and 100 h in a gas mixture containing 0.9448 atm of N2, 0.031 atm of H2O,
      and 0.0242 atm of H2S. The scales consisted primarily of rutile TiO2 and
      amorphous SiO2. Oxidation prevailed, and a small amount of sulfur was present
      over the whole scale, including the scale/matrix interface. Despite the hostile
      oxidizing, sulfidizing, and hydriding gas environments, Ti3SiC2 displayed
      relatively good corrosion resistance due to the formation of SiO2 in addition to
      TiO2.

PMID- 25958585
TI  - The magnetic properties and microstructure of Co-Pt thin films using wet etching
      process.
AB  - Perpendicular magnetic recording (PMR) is a promising candidate for high density
      magnetic recording and has already been applied to hard disk drive (HDD) systems.
      However, media noise still limits the recording density. To reduce the media
      noise and achieve a high signal-to-noise ratio (SNR) in hard disk media, the
      grains of the magnetic layer must be magnetically isolated from each other. This
      study examined whether sputter-deposited Co-Pt thin films can have adjacent
      grains that are physically isolated. To accomplish this, the effects of the
      sputtering conditions and wet etching process on magnetic properties and the
      microstructure of the films were investigated. The film structure was Co-Pt (30
      nm)/Ru (30 nm)/NiFe (10 nm)/Ta (5 nm). The composition of the Co-Pt thin films
      was Co-30.7 at.% Pt. The Co-Pt thin films were deposited in Ar gas at 5, 10,
      12.5, and 15 mTorr. Wet etching process was performed using 7% nitric acid
      solution at room temperature. These films had high out-of-plane coercivity of up
      to 7032 Oe, which is twice that of the as-deposited film. These results suggest
      that wet etched Co-Pt thin films have weaker exchange coupling and enhanced out
      of-plane coercivity, which would reduce the medium noise.

PMID- 25958586
TI  - NiO/CeO2-ZnO nano-catalysts for direct synthesis of dimethyl carbonate from
      methanol and carbon dioxide.
AB  - XNiO/CeO2(0.7)-ZnO(0.3) (X = 0, 1, 5, 10, and 15) nano-catalysts were prepared by
      a wet impregnation method with a variation of NiO content (X, wt%). The prepared
      catalysts were then applied to the direct synthesis of dimethyl carbonate from
      methanol and carbon dioxide. Successful formation of XNiO/CeO2(0.7)-ZnO(0.3) nano
      catalysts was confirmed by XRD and ICP-AES analyses. Acidity and basicity of
      XNiO/CeO2-ZnO were measured by NH3-TPD (temperature-programmed desorption) and
      CO2-TPD experiments, respectively, with an aim of elucidating the effect of
      acidity and basicity of the catalysts on the catalytic performance in the
      reaction. It was revealed that the catalytic activity of XNiO/CeO2(0.7)-ZnO(0.3)
      was closely related to both acidity and basicity of the catalysts. The amount of
      dimethyl carbonate produced over XNiO/CeO2(0.7)-ZnO(0.3) increased with
      increasing acidity and basicity of the catalysts. Thus, both acidity and basicity
      of the catalysts played important roles in determining the catalytic performance
      in the direct synthesis of dimethyl carbonate from methanol and carbon dioxide.

PMID- 25958587
TI  - Preparation and atomic force microscopy (AFM) characterization of DNA scaffolds
      as a template for protein immobilization.
AB  - The design of DNA nanostructures is of fundamental importance, the intrinsic
      value of DNA as a building-block material lies in its ability to organize other
      bio-molecules with nanometer-scale spacing. Here, we report the fabrication of
      DNA scaffolds with nano-pores (< 10 nm size) that formed easily without the use
      of additives (i.e., avidin, biotin, polyamine, or inorganic materials) into large
      scale DNA nanostructures by controlling buffer pH and reaction temperature. Large
      scale DNA scaffolds with porous structures are stable and uniform at slightly
      acidic buffer pH values (pH 5.5) and at approximately room temperature (- 30
      degrees C). The depth of the DNA scaffolds with randomly porous size (< 10 nm)
      was a maximum of approximately 8 nm. Protein immobilization results also
      confirmed that a fibronectin (FN) proteins/large scale DNA
      scaffolds/aminopropylytriethoxysilane (APS)/SiO2/Si substrate with high
      sensitivity formed in a well-defined manner. The DNA scaffolds can be applied for
      use with DNA based biochips, biophysics, and cell biology.

PMID- 25958589
TI  - Synthesis and characterization of multi-functional ZnO nano ceramic phosphor.
AB  - This manuscript reports on the synthesis and characterization of a multi
      functional ZnO core-shell structure with CoFe2O4 as magnetic materials. To form a
      combination between optical (ZnO) and magnetic (CoFe2O4) materials, the surfaces
      of both materials were modified by amine and silica. First, ZnO raw mertials were
      coated silica using sol-gel methods and -OH group of their surface were modified
      using amines. Hydrophobic CoFe2O4 nanoparticle was coated with silica and was
      found to have hydrophilic properties. CoFe2O4 attached silica-coated ZnO core
      shell structures were prepared by self-assembly technique and have blue
      luminescence and magnetic properties.

PMID- 25958588
TI  - Magnetofluorescent probe of superparamagnetic iron oxide nanoparticles modified
      with poly(TMSMA-r-PEGMA-r-Eu(NTA)3(MMA)(TOPO)3).
AB  - In this study, hybrid magnetofluorescent structures composed of organic moiety of
      poly(TMSMA-r-PEGMA) for biomolecules-resistant surfaces and methyl methacrylate
      for conjugation of europium complex inorganic moiety of magnetic nanoparticles
      are reported. Lanthanide complex of europium ion with 4,4,4-Trifluoro-1-(2
      naphthyl)-1,3-butanedione (NTA) and trioctylphosphine oxide
      (TOPO)[Eu(NTA)3(TOPO)3] were incorporated into poly(TMSMA-r-PEGMA-r-MMA) matrix.
      Afterward, superparamagnetic iron oxide nanoparticles (SPIONs) were coated with
      as prepared polymeric europium complex (PEC) to construct hierarchical structure
      of magnetofluorescent probe. The PL spectra of the PEC@SPIONs excited by UV light
      showed characteristic emission behavior with a hypersensitive transition 5D0 -->
      7F2 at 621 nm. About a 20% quenching in the intensity of the emission peak at 621
      nm was found after the addition of SPIONs. Interestingly, when the concentration
      of PEC against SPIONs is increased, the hypersensitive transition 5D0 --> 7F2 at
      621 nm is linearly increased, while 5D1 --> 7F6 at 700 nm is linearly decreased.
      The cytotoxic effect of PEC@SPIONs was evaluated with U373MG cell by the MTT
      assay of PEC@SPIONs in cell proliferation. The cell viability in the range of 10
      200 ug/ml was more than 80%. No significant difference in cell proliferation
      until the concentration of 300 ug/ml (77.61 +/- 3.33%). The cellular uptake of
      PEC@SPIONs evaluated by confocal microscopy showed that the magnetofluorescent
      nanoparticles were internalized extensively in the cytoplasmic region.

PMID- 25958591
TI  - Fabrication of dual dye-doped silica nanotube as a fluorescent ratiometric pH
      sensor.
AB  - This study described a novel fabrication of fluorescence co-encapsulating silica
      nanotubes (F@SNT) and the further application of the as-synthesized nanostructure
      as a ratiometric pH sensor in buffer solution. Silica nanotubes (SNTs) embedded
      anodic alumina oxide (AAO) template was fabricated by sol-gel technique,
      tetramethyl rhodamine (TMR-the reference dye) was incorporated directly onto
      silica layer via hydrophobic interaction. Subsequently, fluorescent
      isothiocyanate (FITC-pH sensitive dye) was encapsulated inside poly
      dimethylsiloxane (PDMS) matrix and the FITC-PDMS nanocomposite was doped into the
      hollow structure of SNT using nano-molding lithography. On removing AAO, free
      standing SNTs were obtained and were subsequently applied as a ratiometric pH
      sensor in phosphate buffer solution. The dual dye-doped SNTs showed excellent
      fluorescence and a good pH sensing performance from pH 5.2-8.0. The results were
      distinguishable by the emission spectra and by fluorescent visualization. High
      photostability, sensitivity, biocompatibility with adjustable sizes make dual dye
      doped-SNT a promising nanostructure for bioapplications.

PMID- 25958590
TI  - Dielectric functions of solution-processed GdAlO(x)/Si films measured with vacuum
      ultra-violet spectroscopic ellipsometry.
AB  - The dielectric functions of amorphous GdAlO(x) (GAO) films grown by the sol-gel
      process were investigated from 1.12 to 8.5 eV as a function of annealing
      temperature using spectroscopic ellipsometry (SE). A GAO precursor sol with a
      molar ratio of Gd:Al = 1:1 was prepared. Thin layers were formed by spin-coating
      on p-type Si substrates. The layers were sintered at 400 degrees C for 2 h in an
      ambient atmosphere, then rapid-thermal-annealed (RTA) at 700 or 800 degrees C for
      1 min in an N2 ambient. The optical properties were measured via variable angle
      SE, at room temperature. The angle of incidence was varied from 50 to 70 degrees
      in 10 degrees steps. The dielectric functions of the resulting GAO films were
      obtained from the measured pseudodielectric functions by multilayer-structure
      calculations using the Tauc-Lorentz (TL) dispersion relation. The real and
      imaginary parts of the dielectric functions were found to increase with
      increasing RTA temperature. The film thicknesses and TL parameters (threshold
      energy E(g) and broadening C) decrease with increasing RTA temperature.

PMID- 25958593
TI  - Microstructural refinement of Al-Si alloy upon ultrasonic nanocrystalline surface
      modification treatment.
AB  - In this work, an Al-7 wt.% Si alloy, which is widely used as the structural
      materials in the automotive and aerospace industries for their high specific
      strength, was subjected to ultrasonic nanocrystalline surface modification (UNSM)
      treatment. After UNSM treatment, the effect of UNSM on the microstructural
      evolution of both Al grain and the dispersed Si particles was studied by using
      scanning electron microscope (SEM) and transmission electron microscope (TEM).
      Experimental results show that the ultra-fine grain (UFG, - 400 nm in size)
      structure is developed in the top surface layer (up to - 15 MUm in depth). The
      coarse Si particles were refined and well dispersed in the UFG Al matrix. Cross
      sectional TEM observation revealed that the grain refinement mechanism involved
      the formation of new grain boundaries dividing the coarse grain into UFG
      structure. Nanotwin and nanosize Si were formed within the original coarse Si
      particles. The presence of dispersed Si particles in the Al matrix accelerated
      the Al grain refinement process.

PMID- 25958592
TI  - Hydrothermal synthesis and photoluminescence investigation of NaY(MoO4)2:Eu3+
      nanophosphor.
AB  - An intense red-emitting NaY(MoO4)2:Eu3+ nanophosphor was developed using a
      hydrothermal technique. A highly pure and single-phase NaY(MoO4)2:Eu3+ nanopowder
      was obtained after sintering the as-prepared sample at 800 degrees C. The crystal
      structure and photoluminescence properties of this double molybdate were
      investigated. X-ray diffraction analysis showed that the NaY(MoO4)2 nanoparticles
      have a scheelite-type tetragonal structure, without mixed phases. Rietveld
      analysis provided the atomic coordinates and Mo-O-rare-earth angles. The
      morphology of the molybdate precursor was controlled by adjusting the synthesis
      conditions. The pH was found to play a crucial role in the particle size and
      morphology distribution. The crystalline powder phosphor exhibited intense and
      efficient red emissions attributed to efficient energy-transfer from MoO4(2-) to
      Eu3+. The chromaticity coordinates (x,y) of the NaY(MoO4)2:Eu3+ phosphor sample
      correspond to (0.662, 0.337). The NaY(MoO4)2:Eu3+ powder exhibited a deep-red
      emission under near-ultraviolet (UV) excitation, indicating a promising red
      phosphor for white-light-emitting diodes based on near-UV light-emitting diodes.

PMID- 25958594
TI  - Size-dependent activation energy and carrier dynamics in Cd(x)Zn(1-x)Te/ZnTe
      quantum dots on Si substrates.
AB  - We investigate the size-dependent activation energy and carrier dynamics in
      Cd(x)Zn(1-x)Te/ZnTe quantum dots (QDs) grown on Si substrates. The excitonic peak
      corresponding to transitions from the ground electronic subband to the ground
      heavy-hole band in Cd0.6Zn0.4Te/ZnTe QDs shifts to a lower energy with increasing
      Cd0.6Zn0.4Te thickness owing to an increase in the size of the QDs. The
      activation energy of the electrons confined in the Cd0.6Zn0.4Te/ZnTe QDs, as
      obtained from the temperature-dependent photoluminescence (PL) spectra, increases
      with increasing Cd0.6Zn0.4Te thickness owing to an enhancement of the quantum
      confinement effect resulting from an increase in the energy difference between
      the electronic state and the conduction band edge. The carrier dynamics of
      Cd0.6Zn0.4Te/ZnTe QDs is studied using time-resolved PL measurements, which shows
      a longer exciton lifetime for Cd0.6Zn0.4Te/ZnTe QDs with increasing Cd0.6Zn0.4Te
      thickness. This behavior is attributed to the reduction of the exciton oscillator
      strength resulting from a strong built-in electric field in the larger QDs.

PMID- 25958595
TI  - Properties of magnetic nanoparticles prepared by co-precipitation.
AB  - Magnetic nanoparticles were synthesized by the addition of ammonium hydroxide to
      an iron chloride solution by chemical co-precipitation. In order to examine
      systematically the crystal phase, average size, and magnetic properties of the
      magnetic nanoparticles, the following were used as experimental parameters: molar
      ratio of Fe2+/Fe3+, composition of the iron chloride solution, amount of ammonium
      hydroxide, reaction temperature, and oxidation time of reaction precipitate. In
      the processing conditions of Fe2+/Fe3+ ratios of 0.5 and 1.0, iron chloride
      solutions of 0.1-0.8 m, NH4OH molar ratios of 6-14R, reaction temperatures of 25
      80 degrees C, and oxidation times of 5-90 min, the co-precipitated nanoparticles
      were observed to exist as a single phase of Fe3O4. The average size of the
      particles was approximately 20 nm, and their magnetization was saturated at about
      60 emu/g with superparamagnetism. When the iron chloride solution comprised only
      Fe2+ ions, the oxidation of the reaction precipitates also developed a Fe3O4
      phase. However, the particle size reached 78 nm with increasing oxidation times,
      and the saturation magnetization increased significantly to 82 emu/g while its
      coercive force was 150 Oe, which indicated that the nanoparticles were
      paramagnetic.

PMID- 25958596
TI  - Dimensionality dependent magnetic and magnetocaloric response of La0.6Ca0.4MnO3
      manganite.
AB  - We report the sol-gel synthesis and impact of reduced dimensionality on the
      magnetocaloric properties of La0.6Ca0.4MnO3 manganite. The synthesized powders
      were characterized by using X-ray diffraction (XRD), field emission scanning
      electron microscopy (FE-SEM) and magnetization measurements. The XRD results
      indicated that the La0.6Ca0.4MnO3 nanoparticles have single phase nature with
      orthorhombic structure. FE-SEM results suggested that the nanoparticles are
      agglomerated and crystallite size increases with the annealing temperature.
      Magnetization measurements show that the La0.6Ca0.4MnO3 nanoparticles exhibit
      transition temperature (T(c)) below room temperature. The transition temperature
      was found to increase with the increasing the crystallite size. Maximum in
      magnetic entropy change, (DeltaS(M))(max) shows interesting behaviour and was
      found to vary with the particle size. At magnetic field of 1 T, the value of
      (DeltaS(M))(max) - 0.13 J/kg K was observed at 213 K for the sample annealed at
      600 degrees C. Also, the increment in the value of (DeltaS(M))(max) was observed
      at higher annealing temperature. This study shows that the magnetic entropy of
      pervoskite manganite can be tuned by tuning the crystallite size of the
      manganites.

PMID- 25958597
TI  - Preparation and characterization of copper-graphite composites by electrical
      explosion of wire in liquid.
AB  - Copper-graphite nanocomposites containing 5 vol.% graphite were prepared by a
      powder metallurgy route using an electrical wire explosion (EEW) in liquid method
      and spark plasma sintering (SPS) process. Graphite rods with a 0.3 mm diameter
      and copper wire with a 0.2 mm diameter were used as raw materials for EEWin
      liquid. To compare, a pure copper and copper-graphite mixture was also prepared.
      The fabricated graphite was in the form of a nanosheet, onto which copper
      particles were coated. Sintering was performed at 900 degrees C at a heating rate
      of 30 degrees C/min for 10 min and under a pressure of 70 MPa. The density of the
      sintered composite samples was measured by the Archimedes method. A wear test was
      performed by a ball-on-disc tribometer under dry conditions at room temperature
      in air. The presence of graphite effectively reduced the wear of composites. The
      copper-graphite nanocomposites prepared by EEW had lower wear rates than pure
      copper material and simple mixed copper-graphite.

PMID- 25958598
TI  - The correlation between the structural and luminescent properties of Ca2SiO4:Eu2+
      nanopowders prepared by the sol-gel process.
AB  - Ca2SiO4:Eu2+ powders were prepared by the sol-gel process using calcium nitrate
      hydrate, europium nitrate hydrate, and tetraethyl orthosilicate (TEOS). The
      effects of the amount of TEOS, firing temperatures, and the Eu2+ concentration on
      the structural and luminescence properties were investigated. The CaO impurity
      phase was produced and it strongly contributed to emission properties. The
      prepared powders were composed of irregular-shaped particles, square plates
      (CaO), and/or needle-shaped particles, depending on the amount of TEOS, while
      with excess TEOS content (1.2 M), Ca2SiO4:Eu2+ crystals were contained in the
      glass matrix. The photoluminescence excitation (PLE) spectra of the synthesized
      powders widely covered from 250 to 450 nm. The related PL emission spectra showed
      green emissions (- 510 nm), which resulted from two overlapped Gaussian emission
      bands centered at 502 and 550 nm assigned to the 4f(7)-4f(6)5d1 transitions of
      the Eu(II) and Eu(I) sites, respectively. Eu2+ ions were incorporated into CaO as
      well as Ca2SiO4, and thus the Eu2+ concentration in Ca2SiO4 was adjusted by the
      amount of the CaO phase in samples. As a result, the strongest green emission of
      Ca2SiO4:Eu2+ was obtained with 0.9 M TEOS.

PMID- 25958599
TI  - Effect of laser fluence on electrical properties of (Sr0.75,La0.25)TiO3 thin
      films grown by pulsed-laser-deposition.
AB  - We have grown Sr0.75La0.25TiO3 (SLTO) thin films using pulsed laser deposition
      (PLD) with various laser energy fluences. We investigated the effect of energy
      fluence on the compositions of SLTO films. The stoichiometry of SLTO films was
      controlled by adjusting the laser energy density. At low energy densities below
      1.0 J/cm2, SLTO films become non-stoichiometric with Ti deficiency. The Ti
      deficiency increases with decreasing the laser energy fluence. We have also
      investigated the effect of laser energy fluence on the electrical properties of
      the thin films. The electrical resistivity and carrier density intimately depend
      on the laser energy fluence as a result of the non-stoichiometry. After
      eliminating the effect of oxygen vacancies by post-annealing, the electrical
      properties are dependent on the cation stoichiometry in the oxide films.

PMID- 25958600
TI  - UV enhanced synthesis of high density Au coated ZnO nanocomposite.
AB  - We report the synthesis of high density Au coated ZnO nanocomposites by UV
      irradiation using a mixed solution of ZnO nanowires, HAuCl4 and Na2CO3. This
      synthesis process is easier and faster than a hydrothermal process in
      synthesizing Au/ZnO nanocomposites. The morphology, size distribution and density
      of the Au nanoparticles on the ZnO nanowires, which affect the photocatalytic
      efficiency of the synthesized Au/ZnO nanocomposite, were affected by the pH of
      the mixed solution. In order to obtain damage-free ZnO nanowires and small Au
      nanoparticles, the pH of the mixed solution should be adjusted to 7-8. UV
      irradiation promoted the formation of metallic Au nuclei, regardless of the
      presence of a ZnO photocatalyst. Au/ZnO nanocomposites were fabricated by Au
      reduction due to UV irradiation, followed by attachment of metallic Au nuclei to
      the ZnO nanowires, rather than by the photocatalytic reaction of ZnO. We propose
      this process as the dominent mechanism of the UV enhanced synthesis of Au/ZnO
      nanocomposites.

PMID- 25958601
TI  - Palladium nanoparticles decorated mesoporous carbon spheres as catalyst for
      reduction of 4-nitrophenol.
AB  - Two kinds of polyaromatics with mesoporous have been synthesized from aromatic
      hydrocarbons using anhydrous zinc chloride as the Friedel-Crafts catalyst and
      chloromethyl methyl ether as a cross-linker, after the Pd nanoparticles (PdNPs)
      decorated on the mesoporous carbon spheres (Pd@CSs) have been prepared by simply
      mixing the as-prepared polyaromatics (polynaphthalene or polypyrene) with PdCl2,
      reducing the Pd2+ to Pd0 by using NaBH4, followed by thermal treatment at 600
      degrees C for 5 h in nitrogen atmosphere. The synthesized PdNPs have a uniform
      size distribution with an average size smaller than 15 nm and they can be loaded
      on the highly mesoporous carbon microspheres. Structural of the resulting Pd@CSs
      were carried out using FE-SEM, HR-TEM, X-ray differaction, dispersive X-ray
      spectroscopy. The resulting Pd@CSs have been investigated as a catalyst for the
      reduction of 4-nitrophenol to 4-aminophenol, showing the Pd@CSs have high
      catalytic reactivity and recyclability.

PMID- 25958602
TI  - Shape control of magnesium oxysulfate granules using an ethanolamine chelate.
AB  - Shape control of inorganic nanomaterials during hydrothermal syntheses is crucial
      for fine-tuning the function of these materials, which are widely utilized in
      semiconductors, ceramics, and optical devices. In particular, magnesium compounds
      possess many desirable physical properties such as high thermal stability, wide
      band gap and high secondary electron emission yield, which allow their
      application as polymeric resins, cements, reinforcements, and fillers. However,
      conventional synthetic methods often require extreme reaction conditions such as
      high temperatures, high pressures, or prolonged reaction times. Additionally,
      various shape control methods are typically quite complicated and time consuming
      under conventional parameters. In this work, magnesium oxysulfate (5Mg(OH)2 x
      MgSO4 x 3H2O) granules of various shapes were fabricated by introducing
      ethanolamine chelate during hydrothermal reaction at a relatively low temperature
      and pressure. The strong interaction between ethanolamine and Mg2+ produced
      5Mg(OH)2 x MgSO4 x 3H2O granules in the form of flakes, flowers, or whiskers
      through self-assembly this formation is dependent on concentration, reaction
      time, and temperature. The physicochemical properties of the samples were
      investigated using X-ray diffraction, field emission scanning electron
      microscopy, transmission electron microscopy, Fourier transform infrared
      spectroscopy, and thermogravimetric analysis.

PMID- 25958603
TI  - Comparison of properties of poly(vinyl alcohol) nanocomposites containing two
      different clays.
AB  - Morphologies, thermo-optical properties, and gas barriers of poly(vinyl alcohol)
      (PVA) hybrid films containing two different clays are compared. Saponite (SPT)
      and hydrophilic bentonite (BTT) were used as the reinforcing filler in the
      fabrication of PVA hybrid films, which were synthesized from aqueous solutions
      and were solvent-cast at room temperature under vacuum, yielding 20-31-MUm-thick
      PVA hybrid films with varying clay contents. The addition of small amounts of
      clay is sufficient to improve the thermal properties and gas barriers of PVA
      hybrid films. Even polymers with a low clay content (3-10 wt%) were found to
      exhibit much higher transition temperature values than pure PVA. The addition of
      BTT was more effective than the addition of SPT for improving the thermal
      properties and gas barrier in the PVA matrix. The PVA hybrid films containing 5
      wt% SPT were equibiaxially stretched, with stretching ratios ranging from 150% to
      250%. Clay dispersion, morphology, optical transparency, and gas permeability
      were then examined as a function of the equibiaxial stretching ratio. PVA hybrid
      films with a stretching ratio of >= 150% displayed homogeneously dispersed clay
      within the polymer matrix and exfoliated nanocomposites.

PMID- 25958604
TI  - Influence of thickness variation on perpendicular magnetic anisotropy features of
      the [co/pt]n multilayer frame.
AB  - We report the structural and magnetic properties of a [Co/Pt] multilayer matrix
      as a function of Pt thickness. Increasing Pt thickness allows for the formation
      of a well-aligned fcc (111) CoPt3 structure in a [Co/Pt]n multilayer geometry,
      where the clear appearance of main (111) peak of CoPt3 measured using the X-ray
      diffraction patterns was confirmed. High-resolution transmission electron
      microscopy images, along with the corresponding fast Fourier transform patterns
      displayed the ordered structure with clear 6-fold symmetric diffraction spots.
      The c/a lattice constant ratio of 0.949 was calculated by utilizing the XRD and,
      demonstrating the presence of a well-aligned CoPt3 structure. The Pt thickness
      dependent saturation magnetization (M(s)) values for the in- and out-of-plane M-H
      hysteresis loops obtained by vibrating sample magnetometer measurements showed
      distinctly opposite trends. The increase in the out-of-plane M(s) value with
      increasing Pt thickness seems to originate from the enhanced perpendicular
      orbital moment of the proper CoPt3 structure.

PMID- 25958605
TI  - Adsorption properties of argon on Ti doped SBA-15.
AB  - Thermodynamic properties of argon on Ti doped Santa barbara amorphous No. 15 (SBA
      15) were investigated in the temperature range of 77-89 K to understand the
      interaction of gas molecules with porous materials. When the total amount of
      adsorbed molecules is plotted as a function of the equilibrium vapor pressure of
      the adsorbed Ar, the results exhibit two distinct isotherm steps. The first step
      appears at the beginning of the isotherm while the second step locates at 0.7 of
      the normalized pressure. The existence of the second isotherm step which spanned
      in the normalized pressure from 0.7 to 0.9 is confirmed when the isotherm data
      were plotted in terms of the 2-dimensional compressibility values. The total
      amount of adsorbed molecules forming the second isotherm step is 2.5 times
      greater than the one for the first step. These adsorption behaviors are typical
      patterns noted from porous materials and far different from the ones observed
      from non-pore materials. Our observations demonstrate that most of adsorbed
      molecules reside in the pores and the height of the second isotherm step is
      strongly associated with filling pores with gas molecules.

PMID- 25958606
TI  - Spherulitic assembly of peptide nanowires via spontaneous crystallization.
AB  - In this work, the hierarchal arrangement of peptide nanowires was achieved via
      the spontaneous crystallization of peptide molecules. Peptide molecules, which
      are structural motifs associated with Alzheimer's disease, assembled into one
      dimensional nanowires and spontaneously formed two-dimensional peptide
      spherulites during crystallization of the peptide melt. The assembly behavior of
      the peptides could be directed by physically confining the soft mold.
      Furthermore, a hybrid assembly of small functional molecules, such as
      photoluminescent Alq3, was also achieved. Our approach offers a simple method for
      achieving spontaneous long-range crystalline order of building blocks approaching
      macroscopic dimensions and also a facile hybridization strategy to conjugate
      biomolecules and functional small molecules.

PMID- 25958607
TI  - Thermal annealing effects on ZnO films grown on graphene buffered Si substrates.
AB  - ZnO films deposited on SiO2/Si substrate with a graphene single layer (GSL) were
      studied by using an ultra-high vacuum sputter. The as-prepared films were
      annealed at temperature ranges from 500 degrees C to 800 degrees C for 1 min
      under ambient N2 gas. When the annealing temperature was increased up to 800
      degrees C, the root mean square roughness of the ZnO/Si sample surface decreased
      down to 3.4 nm, and the grain sizes increased about 50.8 nm with a clear grain
      boundary. From the photoluminescence (PL) spectra, the high intensity of near
      band-edge UV emission at 380 nm (3.26 eV) and the broad band emission between 450
      and 650 nm, known as the visible defect related PL band, decreased with
      increasing annealing temperature up to 800 degrees C. The ZnO thin films on the
      growth on the GSL and post-annealing at 700 degrees C for 1 min under ambient N2
      gas had the best structural and optical properties.

PMID- 25958608
TI  - Effect of Ag nanowire addition into nanoparticle paste on the conductivity of Ag
      patterns printed by gravure offset method.
AB  - This paper focuses on the effect of Ag nanowire addition into a commercial Ag
      nanopaste and the printability evaluation of the mixed paste by the gravure
      offset printing methodology. Ag nanowires were synthesized by a modified polyol
      method, and a small amount of them was added into a commercial metallic paste
      based on Ag nanoparticles of 50 nm in diameter. Two annealing temperatures were
      selected for comparison, and electrical conductivity was measured by four point
      probe method. As a result, the hybrid mixture could be printed by the gravure
      offset method for patterning fine lines up to 15 MUm width with sharp edges and
      scarce spreading. The addition of the Ag nanowires was significantly efficient
      for enhancement of electrical conductivity of the printed lines annealed at a low
      temperature (150 degrees C), while the effect was somewhat diluted in case of
      high temperature annealing (200 degrees C). The experimental results were
      discussed with the conduction mechanism in the printed conductive circuits with a
      schematic description of the electron flows in the printed lines.

PMID- 25958609
TI  - Facile synthesis of ZnO-poly(2-hydroxyethyl methacrylate) nanocomposites by
      surface-initiated ARGET atom transfer radical polymerization.
AB  - The covalent attachment of poly(2-hydroxyethyl methacrylate) on ZnO nanoparticles
      (NPs) has been achieved by ARGET ATRP. The polymer chains were grown from the
      surface of ATRP-initiator modified ZnO NPs with a copper (II) catalyst under
      activation of zerovalent copper as a reducing agent. FT-IR, FE-SEM, TEM and TGA
      were employed for the characterization of the nanocomposites. GPC was used to
      determine the molecular weight and PDI of the cleaved polymer. The covalent
      attachment of polymer chains onto the surface of ZnO NPs was sufficiently
      confirmed by FT-IR. In addition, the formation of the polymer encapsulating ZnO
      cores was demonstrated from TEM and SEM images. It was found that the growing of
      polymer brushes from the ZnO surface could be induced even though the catalyst
      amount was reduced to 10 ppm without loss of inherent control manner. This report
      contributed to demonstrate the versatility and feasibility of ATRP-based surface
      initiated polymerization for the preparation of inorganic/polymer nanocomposites.

PMID- 25958610
TI  - Microporous and mesoporous ZSM-5 catalyst for catalytic cracking of C5 raffinate
      to light olefins.
AB  - ZSM5 catalysts (PAM(X)-ZSM5) with micropores and mesopores were prepared using
      polyacrylamide (PAM) as a soft template at different PAM content (X = 0, 0.12,
      0.25, 0.53, 0.64, and 0.78 wt%), and they were applied to the production of light
      olefins (ethylene and propylene) through catalytic cracking of C5 raffinate. The
      effect of PAM content of PAM(X)-ZSM5 catalysts on the physicochemical properties
      and catalytic activities was investigated. N2 adsorption-desorption isotherms of
      PAM(X)-ZSM5 catalysts exhibited a broad hysteresis loop at high relative
      pressure, indicating the existence of mesopores in the catalysts. It was found
      that the catalytic performance of PAM(X)-ZSM5 catalysts was closely related to
      the mesoporosity of the catalysts. Conversion of C5 raffinate and yield for light
      olefins showed volcano-shaped trends with respect to mesopore/micropore volume
      ratio of the catalysts. Thus, an optimal PAM content was required to achieve
      maximum production of light olefins through catalytic cracking of C5 raffinate
      over microporous and mesoporous PAM(X)-ZSM5 catalysts.

PMID- 25958611
TI  - Solid solution cermet: (Ti,Nb)(CN)-Ni cermet.
AB  - Solid solution powders without W, (Ti,Nb)(CN) powders with a B1 structure (NaCl
      like), were synthesized by high energy milling and carbothermal reduction in
      nitrogen. The range of molar ratios of Ti/Nb for forming complete (Ti,Nb)(CN)
      phase was broader than that of Ti/W for the (Ti,W)(CN) phase because carbide or
      carbonitride of Nb had a B1 crystal structure identical to Ti(CN) while WC had a
      hexagonal crystal structure. The results revealed that the hardness of
      (Ti,Nb)(CN)-Ni cermets was higher than that of (Ti,W)(CN)-Ni cermets. The lower
      density of the (Ti,Nb)(CN) powder contributed to the higher hardness compared to
      (Ti,W)(CN) because the volumetric ratio of (Ti,Nb)(CN) in the (Ti,Nb)(CN)-Ni
      cermets was higher than that of (Ti,Nb)(CN) in the (Ti,W)(CN)-Ni cermets at the
      same weight ratio of Ni. Additionally, it was assumed that intrinsic the
      properties of (Ti,Nb)(CN) could also be the cause for the high hardness of the
      (Ti,Nb)(CN)-Ni cermets.

PMID- 25958612
TI  - Catalytic properties of highly ordered crystalline nanoporous tungsten oxide in
      butanol dehydration.
AB  - Highly ordered mesoporous tungsten oxide (meso-WO3) was successfully synthesized
      using mesoporous silica KIT-6 as a hard template via the nanoreplication method.
      The physicochemical properties of meso-WO3 were characterized by X-ray
      diffraction, nitrogen adsorption-desorption, transmission electron microscopy, X
      ray photoelectron spectroscopy, temperature-programmed desorption of ammonia, and
      infra-red spectroscopy of adsorbed pyridine. No oxidation state other than WO3
      was observed in the meso-WO3 sample. Lewis acid sites were dominant in meso-WO3,
      which could be confirmed by infra-red spectroscopy of pyridine and temperature
      programmed desorption of ammonia. Its catalytic behavior in 2-butanol dehydration
      was investigated in a fixed bed reactor and compared with that of the WO3/MCM-41
      catalyst prepared by the atomic layer deposition method. The meso-WO3 catalyst
      exhibited higher 2-butanol dehydration activity than that of the WO3/MCM-41
      catalyst, which is ascribed to the stronger acidity as well as higher amount of
      acid sites that are mainly composed of Lewis acid sites in the meso-WO3 catalyst.

PMID- 25958613
TI  - Facile fabrication of a cerium oxide nanorod.
AB  - Nanorods are one-dimensional structures that possess interesting physical and
      electrical properties and have potential applications in various areas. Cerium
      oxide, a very abundant rare earth element, is widely utilized in catalysts of
      exhaust systems, chemical abrasives, electrical devices, oxidant semiconductor
      devices, UV adsorbents, and fluorescence emitting materials. Shape control is
      important for controlling the overall shape and quality of the nanorod during
      synthesis. However, most of the shape control studies of cerium oxide
      nanomaterials in the literature have been performed under high temperature and
      high pressure conditions, which impede industrial mass production. In this study,
      we describe a facile synthesis method for producing Ce(OH)3 nanorods with
      different diameters through the application of the common ion effect principle
      using NH+, Cl-, and OH- ions. The resulting Ce(OH)3 rods were dried to produce
      the corresponding cerium oxide products. Consequently, a one-pot reaction under
      mild conditions allowed for the production of high-quality nanorods after much
      shorter reaction times, with the additional natural release of counter ions under
      reaction equilibrium. The shape and physicochemical properties were characterized
      using various analytical methods, including scanning electron microscopy (SEM), X
      ray diffraction (XRD), energy dispersive spectroscopy (EDS), and Raman
      spectroscopy.

PMID- 25958614
TI  - Formation mechanism of rutile TiO2 rods on fluorine doped tin oxide glass.
AB  - We report the formation mechanism of rutile TiO2 rods grown directly on fluorine
      doped tin oxide (FTO) glass by hydrothermal process at 130 degrees C. Through SEM
      images, we could monitor detailed nucleation and crystal growth process of TiO2
      nanorods. The TiO2 nanorods started to nucleate and grow along the grain
      boundaries of SnO2 on FTO glass. As the reaction time increased, fine TiO2
      nanorods started to encounter each other on (110) faces and merge, resulting in
      growth of micrometer scale rods in [001] direction. Through TEM, SAED, and XRD
      analyses, we propose that the nucleation of TiO2 on SnO2 grain boundaries occurs
      by Ostwald ripening (OR) while the merging of small TiO2 nanorods for the
      formation of larger rods occurs through oriented attachment (OA). The merged
      nanorods grow toward [001] direction to reduce surface energy.

PMID- 25958615
TI  - Functionalized mesoporous silicas with crown ether moieties for selective
      adsorption of lithium ions in artificial sea water.
AB  - Lithium ion has been increasingly recognized in a wide range of industrial
      applications. In this work, we studied on the adsorption of Li+ in the artificial
      seawater with high selectivity using methyl-crown ether (AC-SBA-15) and aza-crown
      ether (HMC-SBA-15) moieties-functionalized mesoporous silica materials. First,
      methyl-crown ether and aza-crown ether moieties-functionalized mesoporous silica
      materials were synthesized via two-step post-synthesis process using a grafting
      method. The functionalized materials were employed to the metal ion adsorption
      from aqueous solution (artificial seawater) containing Li+, Co2+, Cr3+ and Hg2+.
      The prepared hybrid material showed high selectivity for Li+ ion in the
      artificial seawater at pH 8.0. The absorbed amount of Li+ was 73 times higher
      than Cr3+ for aza-crown ether containing AC-SBA-15 as an absorbent. The absorbed
      amount of Co2+ (4.5 x 10(-5) mol/g), Cr3+ (1.5 x 10(-5) mol/g) and Hg2+ (2.25 x
      10(-4) mol/g) were remarkably lower than the case of Li+. On the other hand, the
      absorbed amount of various metal ions of HMC-SBA-15 with amine groups in alky
      chains and crown ether moieties were 1.1 x 10(-3) mol/g for Li+, 5.0 x 10(-5)
      mol/g for Co2+, 2.9 x 10(-4) mol/g for Cr3+, 2.8 x 10(-4) mol/g for Hg2+ mol/g,
      respectively.

PMID- 25958616
TI  - Facile synthesis of one-dimensional iron-oxide/carbon hybrid nanostructures as
      electrocatalysts for oxygen reduction reaction in alkaline media.
AB  - One-dimensional iron-oxide/carbon hybrid nano tubular structures were synthesized
      via anodic aluminium oxide (AAO) template method. Highly unform iron oxide
      nanoparticles and carbon structures were formed simultaneously on the wall
      surface of the AAO template from an iron-oleate precursor by solventless thermal
      decomposition method. The 1D iron-oxide/carbon nanostructures were obtained after
      removing the AAO template. The typical size of the iron oxide nanoparticles was -
      6 nm, and the nanoparticles had a crystalline structure of maghemite (gamma
      Fe2O3), which was determined from the HRTEM and X-ray diffraction (XRD). This
      nanocrystalline spinel structure could provide more active sites for oxygen
      reduction reaction (ORR) catalysis due to the higher specific surface area and
      numerous defects. As an ORR catalyst, the hybrid nanotubes showed higher limiting
      mass activity (8.8 A/g) and a more positive onset potential (-0.241 V, vs.
      Hg/HgCl) than iron oxide nanoparticles in alkaline media. This electrocatalytic
      activity of the nanocomposites is mainly attributed to the synergetic effects of
      the iron oxide nanoparticles and carbon matrix in the one-dimensional
      nanostructure.

PMID- 25958617
TI  - Comparison of microstructures and phase compositions of artificial and bone
      derived hydroxyapatites by transmission electron microscopy and energy dispersive
      electron spectroscopy.
AB  - Biological problems associated with sintered implants fabricated from
      artificially synthesized hydroxyapatite include selective dissolution at grain
      boundaries, microstructural disintegration in the body due to particle loosening,
      and slow crack growth at the implant surface. In addition, mechanical degradation
      has been shown to be significant, thus limiting their application as load-bearing
      medical implants. In contrast, bone-derived hydroxyapatite bioceramics have
      highly dissolution-resistant properties and excellent biocompatibility in the
      body. They are also easy to synthesize by thermal decomposition of animal bone.
      In this study, microstructural observations and crystal phase analysis of bone
      derived hydroxyapatite were investigated by TEM and EDS using sintered
      hydroxyapatite samples. In addition, a comparative investigation into elemental
      distributions and the microstructures of artificial hydroxyapatite, bovine, and
      tuna bone-derived hydroxyapatites was performed. Bone-derived HA consists mainly
      of HA and a small amount of MgO. Hot-pressed HA compacts showed homogeneous
      microstructures and densities of 95-97%, however, grain sizes and microstructures
      varied with the starting powders.

PMID- 25958618
TI  - Evolution of CdTe nanoparticles into nanowires via self-assembly.
AB  - Cadmium telluride (CdTe) nanowires were successfully synthesized from individual
      nanoparticles via self-assembly, and the evolutionary process was investigated.
      The oxidation of tellurium ions in CdTe nanoparticles under dark conditions led
      to the assembly of straight nanowires made of several layers of individual
      nanoparticles. Transmission electron microscopy and scanning electron microscopy
      were performed to characterize the synthesized nanostructures. The length of the
      NWs assembled from CdTe NPs ranged from 0.5 to 30 MUm. Unlike generally prepared
      NWs, these NWs were made from individual NPs layered on top of each other.
      Remarkably, the assembly of individual NPs formed bundles during the intermediate
      steps before they unraveled into individual NWs. Both control of the amount of
      stabilizer and oxidation of Te ions acted as driving forces to form NWs. Thus,
      small modifications in synthesis yielded a major difference in the final
      nanomaterial structure. The suggested synthetic procedure provides a viable
      pathway for the fabrication of nanomaterials.

PMID- 25958619
TI  - Conversion of succinic acid to 1,4-butanediol via dimethyl succinate over rhenium
      nano-catalyst supported on copper-containing mesoporous carbon.
AB  - Copper-containing mesoporous carbons (XCu-MC) with different copper content (X =
      8.0, 12.7, 15.9, 23.3, and 26.8 wt%) were prepared by a single-step surfactant
      templating method. Rhenium nano-catalysts supported on copper-containing
      mesoporous carbons (Re/XCu-MC) were then prepared by an incipient wetness method.
      Re/XCu-MC (X = 8.0, 12.7, 15.9, 23.3, and 26.8 wt%) catalysts were characterized
      by nitrogen adsorption-desorption isotherm, HR-TEM, FT-IR, and H2- TPR analyses.
      Liquid-phase hydrogenation of succinic acid to 1,4-butanediol (BDO) via dimethyl
      succinate (DMS) was carried out over Re/XCu-MC catalysts in a batch reactor. The
      effect of copper content on the physicochemical properties and catalytic
      activities of Re/XCu-MC catalysts in the hydrogenation of succinic acid to BDO
      was investigated. Re/XCu-MC catalysts retained different physicochemical
      properties depending on copper content. In the hydrogenation of succinic acid to
      BDO, yield for BDO showed a volcano-shaped trend with respect to copper content.
      Thus, an optimal copper content was required to achieve maximum catalytic
      performance of Re/XCu-MC. It was also observed that yield for BDO increased with
      increasing the amount of hydrogen consumption by copper in the Re/XCu-MC
      catalysts.

PMID- 25958620
TI  - Scanning tunneling microscopy investigation of nano-structured alpha-K5PW11(M x
      OH2)O39(M = Mn(II), Co(II), Ni(II), and Zn(II)) Keggin heteropolyacid catalyst
      monolayers.
AB  - Nano-structured alpha-K5PW11(M x OH2)O39 (M = Mn(II), Co(II), Ni(II), and Zn(II))
      Keggin heteropolyacids (HPAs) were investigated by scanning tunneling microscopy
      (STM) and tunneling spectroscopy (TS) measurements in order to elucidate their
      redox property and oxidation catalysis. HPA molecules formed two-dimensional self
      assembled monolayer arrays on highly oriented pyrolytic graphite (HOPG) surface.
      Furthermore, HPAs exhibited a distinctive current-voltage behavior referred to as
      negative differential resistance (NDR) phenomenon. The measured NDR peak voltage
      of HPAs was correlated with the reduction potential and the absorption edge
      energy determined by electrochemical method and UV-visible spectroscopy,
      respectively. NDR peak voltage of HPAs appeared at less negative voltage with
      increasing reduction potential and with decreasing UV-visible absorption edge
      energy. The correlations strongly suggested that NDR phenomenon was closely
      related to the redox property of HPAs. Vapor-phase oxidation of benzyl alcohol to
      benzaldehyde was carried out as a model reaction to track the oxidation catalysis
      of HPAs. NDR peak voltage appeared at less negative voltage with increasing yield
      for benzaldehyde.

PMID- 25958621
TI  - Mg3(VO4)2-MgO-ZrO2 nano-catalysts for oxidative dehydrogenation of n-butane.
AB  - A series of X-Mg3(VO4)2-MgO-ZrO2 nano-catalysts with different vanadium content
      (X = 3.3, 5.3, 7.0, 10.2, and 13.4) were prepared by a single-step citric acid
      derived sol-gel method for use in the oxidative dehydrogenation of n-butane to n
      butene and 1,3-butadiene. The effect of vanadium content of X-Mg3(VO4)2-MgO-ZrO2
      nano-catalysts on their physicochemical properties and catalytic activities in
      the oxidative dehydrogenation of n-butane was investigated. Successful formation
      of X-Mg3(VO4)2-MgO-ZrO2 nano-catalysts was confirmed by XRD, Raman spectroscopy,
      and ICP-AES analyses. The catalytic performance of X-Mg3(VO4)2-MgO-ZrO2 nano
      catalysts strongly depended on vanadium content. All the X-Mg3(VO4)2-MgO-ZrO2
      nano-catalysts showed a stable catalytic performance without catalyst
      deactivation during the reaction. Among the catalysts tested, 7.0-Mg3(VO4)2-MgO
      ZrO2 nano-catalyst showed the best catalytic performance in terms of yield for
      total dehydrogenation products (TDP, n-butene and 1,3-butadiene). TPRO
      (temperature-programmed reoxidation) experiments were carried out to measure the
      oxygen capacity of the catalyst. Experimental results revealed that oxygen
      capacity of the catalyst was closely related to the catalytic performance. Yield
      for TDP increased with increasing oxygen capacity of the catalyst.

PMID- 25958623
TI  - Cyclic ligand functionalized mesoporous silica (SBA-15) for selective adsorption
      of Co2+ ion from artificial seawater.
AB  - Hard donor atoms (N and O) containing macrocyclic ligand was synthesized and
      further functionalized with mesoporous SBA-15 materials by chemical modification
      method. The modification was achieved by the immobilization of 3
      chloropropyltriethoxysilane (CIPTES) onto mesoporous silica surface followed by
      post grafting route. The resulting material (Py-Cy-SBA-15) has been characterized
      by low angle X-ray diffraction (XRD), nitrogen adsorption-desorption isotherm,
      Fourier-transform infrared (FT-IR) spectroscopy, 29Si and 13C CP MAS NMR
      spectroscopic analyses, Thermogravimetric analysis (TGA) and elemental analysis.
      The long range orders of the materials were identified by transmission electron
      microscopy (TEM). The functionalized material was employed to the heavy metal
      ions adsorption from aqueous solution containing Cu2+, Co2+, Zn2+, Cd2+ and Cr2+.
      The prepared hybrid material showed high selectivity and adsorption capacity for
      Co2+ ion at pH 8.0.

PMID- 25958622
TI  - Cs(x)H(3.0-x)PW12O40 (X = 2.0-3.0) heteropolyacid nano-catalysts for catalytic
      decomposition of 2,3-dihydrobenzofuran to aromatics.
AB  - Cesium-exchanged Cs(x)H(3.0-x)PW12O40 (X = 2.0, 2.3, 2.5, 2.8, and 3.0)
      heteropolyacid nanocatalysts were prepared, and they were applied to the
      catalytic decomposition of lignin model compound to aromatics. Successful
      formation of cesium-exchanged Cs(x)H(3.0-x)PW12O40 (X = 2.0-3.0) catalysts was
      confirmed by FT-IR, ICP-AES, and XRD measurements. 2,3-Dihydrobenzofuran was
      employed as a lignin model compound for representing beta-5 bond in lignin.
      Phenol, ethylbenzene, and 2-ethylphenol were mainly produced by the catalytic
      decomposition of 2,3-dihydrobenzofuran. Conversion of 2,3-dihydrobenzofuran and
      total yield for main products (phenol, ethylbenzene, and 2-ethylphenol) were
      closely related to the surface acidity of Cs(x)H(3.0-x)PW12O40 (X = 2.0-3.0)
      catalysts. Conversion of 2,3-dihydrobenzofuran and total yield for main products
      increased with increasing surface acidity of the catalysts. Among the catalysts
      tested, Cs2.5H0.5PW12O40 with the largest surface acidity showed the highest
      conversion of 2,3-dihydrobenzofuran and the highest total yield for main
      products. These results indicate that surface acidity of Cs(x)H(3.0-x)PW12O40 (X
      = 2.0-3.0) catalysts served as an important factor determining the catalytic
      performance in the decomposition of 2,3-dihydrobenzofuran to aromatics.

PMID- 25958624
TI  - Structure analysis and magnetic properties of nano-sized Nb(x)Cu(y)Zn(1-x-y)Fe2O4
      powders formed by self-propagating high-temperature synthesis and ultrasonic
      agitation method.
AB  - Nano-sized Nb0.12Cu0.45Zn0.43Fe2O4 ferrites with an average size of the
      agglomerated particles less than 300 nm were prepared by self-propagating high
      temperature synthesis (SHS) followed by mechanical ball milling and classifying
      by ultrasonic floating agitation. The SHS reaction occurred in the powder mixture
      of iron and various oxides like NbO, CuO, ZnO, Fe2O3 at the oxygen pressure range
      of 0.1 to 1.0 MPa, which average combustion temperatures and combustion
      propagating rates were in the ranges of 1105 to 1343 K and 4.1 to 6.2 mm/s,
      respectively. The combustion temperature increased with the oxygen pressure. The
      combustion reaction did not occur above the uniaxial compacting pressure of 10.0
      MPa, even though the oxygen pressure was 1.0 MPa. The neutron diffraction
      analysis revealed that the final product was Nb0.12Cu0.45Zn0.43Fe2O4 with lattice
      parameters of 0.8472 nm. The maximum magnetization (Ms), residual magnetization
      (M(r)), coercive force (iH0), and susceptibility of the Nb0.12Cu0.45Zn0.43Fe2O4
      ferrites were 11.30 Wb/m2 Kg, 1.47 Wb/m2 Kg, 7321 A/m, and 0.02 m3/kg,
      respectively. The addition of niobium to copper-zinc ferrites resulted in
      increasing M(s), M(r), and iM(c) by about 49%, 68%, and 287%, respectively. The
      variation of the magnetic properties is related to the non-stoichiometric numbers
      and oxygen position of the niobium-copper-zinc ferrites.

PMID- 25958625
TI  - Effect of thermal treatment on the nano-structure and phase transformation of
      metakaolin-based geopolymers.
AB  - Enhancement of the mechanical strength of metakaolin-based geopolymers activated
      with NaOH was attempted by calcining metakaolin at a higher temperature than that
      commonly reported. Increasing the calcination temperature from 750 degrees C to
      1150 degrees C promoted the recrystallization of mullite. Two type of zeolite of
      sodium aluminum silicate hydrates were found in the geopolymers made of
      metakaolin calcined at 750 degrees C-1050 degrees C. The h-zeolite [Na6(AlSiO4)6
      x H2O] was not found in the geopolymer made of metakaolin calcined above 900
      degrees C, while Z-zeolite [Na2O x Al2O3 x SiO2 x H2O] remained in specimens
      calcined at up to 1050 degrees C, All zeolite disappeared above 1150 degrees C.
      The pozzolanic reaction generates very small particles of 10-30 nm on the surface
      of metakaolin grains of 0.2-0.6 MUm, rendering the matrix denser by binding the
      grains. The maximum compressive strength was revealed with the geopolymer made of
      metakaolin calcined at 1050 degrees C. The reason for the increased strength of
      the geopolymer obtained using higher calcination temperature is thought to be the
      combined effects of matrix hardening by geopolymeric reaction and reinforcement
      by mullite crystal phases.

PMID- 25958626
TI  - [Meta-analysis on the relationship among fiber of grain and intestinal motility
      and symptoms].
AB  - OBJECTIVE: To study the relationship among fiber of grain and intestinal motility
      and symptoms. METHODS: To search all related data of randomized controlled trials
      about fiber of grain on intestinal motility and symptoms published before Jul,
      2013, screen trials according to inclusion and exclusion criteria, extract data
      and evaluate quality by two independent researchers, and analyze data by Meta
      analysis using RevMan 5.2 software. RESULTS: Thirteen researches with 739
      subjects were included. According to Meta-analysis, consumption of grain fiber
      had more frequency of defaecation (WMD = 0.10, 95% CI 0.02 - 0.18, P < 0.05),
      less intestinal transit time (WMD = - 6.36, 95% CI -11.53 (-) - 1.20, P < 0.05),
      more fecal wet weight (WMD = 51.52. 95% CI 31.00 - 72.04, P < 0.05) than control,
      similar bowel side effects (SMD = 0.06, 95% CI - 0.04 - 0.16, P = 0.267), and had
      higher functional bowel disorder remission rate when using per protocol analysis
      (RR = 1.20, 95% CI 1.00 - 1.44, P =0.05 ). However, there was no significant
      increase of functional bowel disorder remission rate (RR = 1.16, 95% CI 0.95 -
      1.41, P = 0.14) when using intention to treat analysis. CONCLUSIONS: Fiber of
      grain may have a positive impact on intestinal motility and no adding
      gastrointestinal side-effect, but may have an uncertain influence on functional
      bowel disorders.

PMID- 25958627
TI  - [Effects of conjugated linoleic acid and exercise on RBP4 of liver and adipose
      tissues in adolescent obese rats].
AB  - OBJECTIVE: To exploer effects of conjugated linoleic acid and exercise on RBP4 of
      liver and adipose tissues in adolescent obese rats. METHODS: 8 adolescent SD rats
      were selected as blank control (C) with normal diet. Obese rats were modeled with
      high fat feeding for 7 weeks. 32 obese rats were selected and randomly divided
      into 4 groups: control group (OC), CLA group ( OCC), exercise group (OM),
      exercise combined with CLA group (OMC). Exercise treatment were performed on
      animal treadmill with running speed of 21 - 25 m/min, 60 min/every time. For CLA
      treatment, each rat was fed 1.6 g/kg, one time/day, 5 times/week, for 8 weeks.
      Animals were anesthesia treated after experiment, blood and body tissues were
      collected. The content of blood glucose was measured, the insulin sensitivity was
      calculated, testing the expression of RBP4 mRNA in visceral adipose tissue,
      expression of RBP4 protein in liver cells and plasma RBP4 concentration. RESULT:
      (1) Weight, weight growth rate and body fat percentage of OM, OMC groups were
      lower than OC, OCC groups (P < 0.01). (2) Blood glucose content of OM, OMC groups
      were significantly lower than OC, OCC groups (P < 0.01), while insulin
      sensitivity of OM, OMC groups was higher than OC, OCC groups (P < 0.01). (3)
      Expression of RBP4 mRNA of OM, OMC groups in visceral adipose tissue was lower
      than OC, OCC groups (P < 0.01). Expression of RBP4 protein of OM, OMC groups in
      liver cells was significantly lower than OC, OCC groups. RBP4 concentration in
      plasma of OM, OMC groups was lower than OC, OCC groups (P < 0.01). (4) Weight,
      weight growth rate, insulin sensitivity of OMC group were higher than OM group,
      but the percentage of body fat, blood glucose content and the expression of RBP4
      were lower than OM group, there were no significant differences between them.
      CONCLUSION: Simple exercise and exercise combined with CLA conld significantly
      reduced adolescent obese rats weight, weight growth rate, percentage of body fat,
      blood glucose content and also reduced RBP4 mRNA expression in visceral adipose
      tissue, RBP4 protein expression in liver tissue, RBP4 level in plasma,but can
      increase sensitivity to insulin, in a word, the treatment of exercise and
      exercise combine with CLA is better than the simple complement of CLA to
      adolescent obese rats.

PMID- 25958628
TI  - [Effects of basic orange II on proliferation and differentiation of limb bud
      cells in rat embryos].
AB  - OBJECTIVE: To explore the effects of basic orange II on proliferation and
      differentiation of limb bud cells. METHODS: Limb bud cell were separated from SD
      rat embryo at 13-day gestational age, limb bud cell were exposed to basic orange
      II at concentrations of 0.0, 12.5, 25.0, 50.0, 100.0, 200, 0 and 400.0 mg/L in
      the culture medium. The effect of basic orange II on limb bud cell proliferation
      was detected by Cell Counting Kit-8, the effect of basic orange II on limb bud
      cell differentiation was assessed by Alcian Blue 8GX. RESULTS: With the
      increasing of basic orange II concentration, the proliferation and
      differentiation of embryo limb bud cells were poorer and poorer in vitro, and
      there was the dose-effect relationship. The pID50 and dLD50 of basic orange II on
      limb bud cells were 240.6 mg/L and 69.3 mg/L respectively. The inhibition of
      basic orange II on cell differentiation might exceed that on cell proliferation.
      CONCLUSIONS: Basic orange II could inhibit proliferation and differentiation of
      embryo limb bud cells. It might be a potential developmental toxic substance in
      rat embryo.

PMID- 25958629
TI  - [Distribution and main influential factors of mental workload of middle school
      teachers in Nanchang City].
AB  - OBJECTIVE: To investigate the distribution and main influential factors of mental
      workload of middle school teachers in Nanchang City. METHODS: A total of 504
      middle school teachers were sampled by random cluster sampling from middle
      schools in Nanchang City, and the mental workload level was assessed with
      National Aeronautics and Space Administration-Task Load Index (NASA-TLX) which
      was verified in reliability and validity. RESULTS: The mental workload scores of
      middle school teachers in Nanchang was approximately normal distribution. The
      mental workload level of middle school teachers aged 31 -35 years old was the
      highest. For those no more than 35 years old, there was positive correlation
      between mental workload and age (r = 0.146, P < 0.05). For those more than 35
      years old, the levels of their mental workload had no statistically significant
      difference. There was a negative correlation between mental workload and
      educational level(r = -0.172, P < 0.05). The middle school teachers with lower
      educational level seemed to have a higher mental workload (P < 0.01). The longer
      a middle school teacher worked per day, the higher the mental workload was.
      Working hours per day was the most influential factor on mental workload in all
      influential factors (P < 0.001). CONCLUSION: Mental workload of middle school
      teachers was closely related to age, educational level and work hours per day.
      Working hours per day was the important risk factor of mental workload. Reducing
      working hours per day, especially reducing it to be no more than 8 hours per day,
      may be a significant and useful approach alleviating mental workload of middle
      school teachers in Nanchang City.

PMID- 25958630
TI  - [Effects of bisphenol A on voltage-dependent T-type calcium channels in mouse
      testis and epididymis, and the role of estrogen receptors].
AB  - OBJECTIVE: To explore the possible effects of bisphenol A (BPA) on voltage
      dependent T-type calcium channels in mouse testis and epididymis, the role of the
      two ERs was also investigated. METHODS: Adult male wild type (WT), ERs knock out
      mice (alphaERKO and betaERKO) were randomly divided into control and BPA [100
      MUg/(kg. d) for 30 days via intragastric administration] treatment groups.
      Quantitative real time PCR was used to examine Cav3.1, Cav3.2 and Cav3.3 genes of
      the testis and epididymis. RESULTS: In the testis, the mRNA expression of Cav3.1,
      Cav3.2 and Cav3.3 were increased in BPA-treated animals. In the epididymis, the
      mRNA expression of Cav3. 1 and Cav3.2 were increased, however, Cav3.3 were
      decreased in BPA-treated animals. BPA up-regulation of Cav3.1 and Cav3.2 mRNA
      expression of the epididymis were dependent on both ERalpha and ERbeta, whereas
      BPA regulation of Cav 3.1 - Cav3.3 of the testis and Cav3.3 of the epididymis
      appeared to be dependent on ERbeta only. CONCLUSION: It suggested that the ERs
      signalling was necessary for the regulation of the Cav3 channels mRNA expression
      by BPA, which could affect the male reproductive function.

PMID- 25958631
TI  - [A case-control study on the relationship of crocidolite pollution in drinking
      water with the risk of gastrointestinal cancer in Dayao County].
AB  - OBJECTIVE: To explore the relationship of crocidolite pollution in drinking water
      with the risk of gastrointestinal cancer's death in Dayao County. METHODS: A 1:2
      matched case-control study involving 54 death cases of gastrointestinal cancer
      from a population-based cohort of twenty-seven years and 108 controls matched by
      age, gender, death time, etc was conducted to analyze the effect of local water
      condition on the risk of gastrointestinal cancer in Dayao County. RESULTS:
      Results from logistic regression analysis suggested the longer of asbestos
      furnace use over time, the higher the mortality risk of gastrointestinal cancer
      (6 - 10 years: OR = 2.920, 95% CI 1.501 - 5.604. 11 - 15 years: OR = 3.966, 95%
      CI 2.156 -7.950. Over 15 years: OR = 4.122, 95% CI 1.211 - 7. 584). Drinking
      unboiled water leaded to an increased risk of gastrointestinal cancer (OR = 1.43,
      95% CI 1.07 - 1.88). Type of drinking water was associated with gastrointestinal
      cancer. When compared with drinking tap water, OR for drinking well water was
      1.770 (95% CI 1.001 - 2.444), 2.442 for drinking river water (95% CI 0.956 -
      3.950), 2.554 for drinking house and field ditch water (95% CI 1.961 - 6.584),
      and 3.121 for drinking pond water (95% CI 1.872 - 6.566). CONCLUSION: Related
      factors of drinking water in crocidolite-contaminated area in Dayao County were
      significantly associated with the mortality of gastrointestinal cancer.

PMID- 25958632
TI  - [Study on the optimization of monitoring indicators of drinking water quality
      during health supervision].
AB  - OBJECTIVE: To optimize non-regular drinking water quality indices (except Giardia
      and Cryptosporidium) of urban drinking water. METHODS: Several methods including
      drinking water quality exceed the standard, the risk of exceeding standard, the
      frequency of detecting concentrations below the detection limit, water quality
      comprehensive index evaluation method, and attribute reduction algorithm of rough
      set theory were applied, redundancy factor of water quality indicators were
      eliminated, control factors that play a leading role in drinking water safety
      were found. RESULTS: Optimization results showed in 62 unconventional water
      quality monitoring indicators of urban drinking water, 42 water quality
      indicators could be optimized reduction by comprehensively evaluation combined
      with attribute reduction of rough set. CONCLUSION: Optimization of the water
      quality monitoring indicators and reduction of monitoring indicators and
      monitoring frequency could ensure the safety of drinking water quality while
      lowering monitoring costs and reducing monitoring pressure of the sanitation
      supervision departments.

PMID- 25958633
TI  - [Cross-sectional association between overall diet quality and pubertal
      development among children and adolescents in Chengdu City].
AB  - OBJECTIVE: To explore the association between overall diet quality and pubertal
      development among children. METHODS: A total of 1713 children and adolescents
      aged 7 - 15 years in Chengdu were recruited by cluster sampling and surveyed
      using food frequency questionnaires to collect information on their intakes and
      frequency of all kinds of foods and drinks over the past year. Diet quality of
      participants was evaluated using Chinese Children Dietary Index. Pubertal
      development was assessed according to the Tanner method. RESULTS: The mean
      dietary index score of boys and girls were 57.57 +/- 11.32 and 59.73 +/- 11.50,
      respectively. The prevalence of spermarche or voice break was lowest among boys
      with higher diet quality. Similarly, girls with higher diet quality had a
      significantly lowest prevalence of menarche. Scores of Chinese Children Dietary
      Index for both boys and girls with higher degree of pubertal development were the
      lowest. CONCLUSION: The overall diet quality of children and adolescents was
      negatively associated with their pubertal development. Moreover, this association
      appeared to be stronger in girls than that in boys.

PMID- 25958634
TI  - [Cross-sectional association between food rich in protein and pubertal
      development among children and adolescents in Chengdu City].
AB  - OBJECTIVE: To explore the association between food rich in protein and puberty
      development among children and adolescents in Chengdu city. METHODS: A total of
      1669 children and adolescents aged 7 - 15 years were recruited in Chengdu with
      cluster sampling. Measurement of pubertal development was conducted among
      boys/girls and information about consumption of foods rich in protein was
      collected from food frequency questionnaire. Rank sum test was used to compare
      food intakes between different pubertal groups. RESULTS: Among boys, the
      consumption of red meat and white meat increased with increasing degree of testis
      volume (P < 0.05). Compared with boys who had spermarche, consumption of red
      meat, white meat and dairy and dairy products were lower in the boys who did not
      (P < 0.05). The consumption of red meat and white meat increased with increasing
      degree of pubertal group and consumption of dairy and dairy products was highest
      in the early pubertal group (P < 0.05). Among girls, bean intake was higher in
      the B1 and B5 group of breast development and consumption of dairy and dairy
      product was highest in the B1 group (P < 0.05). Compared with girls who had
      menarche, red meat intake was lower, however, consumption of dairy and dairy
      product were higher in the girls who did not (P < 0.05). The intake of red meat
      increased with increasing degree of pubertal group in girls, however, the
      consumption of bean, fish and shellfish, egg and dairy and dairy product
      decreased (P < 0.05). CONCLUSION: The consumption of foods rich in protein were
      associated with pubertal development among children and adolescents in Chengdu.
      However, the different influence between genders needs to be further studied.

PMID- 25958635
TI  - [Cross-sectional association between consumption of grain/tubers and pubertal
      development among children and adolescents in Chengdu City].
AB  - OBJECTIVE: To investigate association between the consumption of grain and tubers
      and pubertal development of children and adolescents in Chengdu city. METHODS:
      Cross-sectional valid data from 1902 children and adolescents aged 7 - 18 years
      in Chengdu were analyzed. Based on food frequency questionnaire, the daily
      consumption of grain and tubers was calculated. Measurements of pubertal
      development were conducted among boys/girls. RESULTS: The mean age of spermarche
      was 12.8, and that of menarche was 12.3. Boys who had spermarche consumed more
      grain than those had not yet (P < 0.0001), while girls who had menarche consumed
      less (P < 0.01). Consumption of grain was positively associated with pubertal
      development among boys (P < 0.0001). Both consumption of grain and tubers were
      associated with pubertal development among girls (P < 0.05). CONCLUSION:
      Consumption of grain and tubers seem to be correlated with pubertal development
      among children and adolescents in Chengdu, and the association was not the same
      in each gender.

PMID- 25958636
TI  - [Cross-sectional association between sedentary behaviors and anthropometric
      indexes among children and adolescents in Chengdu City].
AB  - OBJECTIVE: To examine the situation of sedentary behaviors and anthropometric
      indexes among children and adolescents in Chengdu city. METHODS: A total of 2164
      children and adolescents aged 7 - 15 years old were recruited in Chengdu city by
      using cluster random sampling method. This study was a cross-sectional study,
      which aimed to collect data on anthropometry including height and weight etc. and
      information on sedentary behavior by using the self-designed questionnaire.
      RESULTS: The time spent on watching TV, using computer and doing homework was
      longer in boys than that in girls. After having been stratified by gender and age
      groups, the time spent on sedentary behaviors (including watching TV, using
      computer and doing homework) was longer in 13 - 15 age group than that in. 10 -
      12 and 7 -9 age groups in boys. Similar results were obtained in girls. BMI z
      scores and the percentage of body fat (BF%) were higher in girls than that in
      boys (P < 0.0001). BMI z-scores in boys decreased with increasing age after
      having been stratified by gender and age groups and BF% was higher in 10 - 12 age
      group. However, BF% in girls was increased with increasing age (P < 0.0001). As
      three sedentary behaviors were classified into low/high respectively, BF%
      increased with the time spent on watching TV and doing homework increasing in 10 
      12 age group in girls. The time spent on watching TV increased withthe BMI z
      scores increasing. CONCLUSION: The time spending on watching TV, using computer
      and doing homework increased with increasing age among children and adolescents
      in Chengdu. Sedenatry behaviors in girls may be related to BMI z-scores and BF%.

PMID- 25958637
TI  - [Study on the psychological health condition among junior and senior high school
      students in Beijing, Shanghai and Guangzhou].
AB  - OBJECTIVE: To describe the status and difference of students' mental health in
      junior high school, ordinary high school and vocational high school in Beijing,
      Shanghai and Guangzhou. METHODS: 135 schools and 14 473 students were randomly
      selected and stratified to draw the sample. Mental Health Test (MHT) was used to
      measure the status of students' mental health. RESULTS: Among 13 286 valid
      questionnaire, 2.1% students were mentally disabled, more females reported their
      mental problems (2.1%) than males (1.9%). Students from Shanghai (2.5%) and
      Beijing (2.3%) were more likely to report their mental problems than students
      from Guangzhou (1.6%), which were statistically significant. The top three mental
      problems includes anxiety (42.6%), physical condition (11.1%) and self - blame
      tendency (9.7%), etc. CONCLUSION: Students from Beijing, Shanghai and Guangzhou
      got different extend of mental problems.

PMID- 25958638
TI  - [Study on IgE mediated food allergy of 3 -12 years urban children in China].
AB  - OBJECTIVE: To study the situation of IgE-mediated food allergy of Chinese urban
      children, including the rate of food allergy and the main food allergens in
      children. METHODS: All the serum samples were selected from the serum bank built
      by the national nutrition and health survey of Chinese residents. Total IgE of
      all the samples were tested by enzyme linked immunosorbent assay, and the sIgE of
      TIgE-positive samples were then tested by immunoblotting. RESULTS: A total of
      5190 samples were selected from serum bank, and the rate of IgE-mediated food
      allergy was 3.20%. The rate of IgE-mediated food allergy was 2.70% in big cities,
      while it was 3.77% in small and medium-sized cities. The rate was gradually
      decreased with age grown. CONCLUSION: The situation of food allergy in children
      and the main allergens could be preliminary determined by testing the serum total
      IgE level and specific IgE.

PMID- 25958639
TI  - [Investigation on the nutrition labels of prepackaged traditional foods of Henan
      Province].
AB  - OBJECTIVE: To understand the current status of nutrition labeling on Henan
      province local traditional prepackaged food product. METHODS: Purchasing the
      samplings according with the include criteria in the supermarket and retail
      stores within the scope of province, then taking photographs and logging
      nutrition labeling information to questionnaire, using Excel and SPSS 15.0
      software to analyze. The .significance of difference rate was judged by chi
      square test. RESULTS: The sum of meeting requirement samplings was 565 (including
      5 major categories and 13 small classes) and the entire nutritional labeling
      signing rate was 91.9%. The signing rate of forced signing nutrients such as
      energy, protein, carbohydrates, fat and sodium was 98.8%. There were 7 kinds of
      mistakes of nutritional labeling signing. The nutrition labeling signing rate of
      optional nutrients was very low. The signing rate of nutrition claims and
      function claims was less than 4%. CONCLUSION: In the traditional local
      prepackaged food products made in Henan province, the forced signed nutrition
      labeling was well sighed but optional content was ignored.

PMID- 25958640
TI  - [Study on simultaneous contamination of Salmonella and Campylobacter in retail
      chicken carcasses in Beijing].
AB  - OBJECTIVE: To elucidate the simultaneous contamination of Salmonella and
      Campylobacter in retail chicken carcasses in Beijing and to carry out the
      serological typing of all Salmonella isolates as well as the identification of
      Campylobacter at the species level. METHODS: A total of 33 chicken carcasses were
      collected from Beijing supermarkets and farm's trade markets from May to July.
      All samples were enumerated for Salmonella and Campylobacter. All Salmonella
      isolates obtained were further serotyped and Campylobacter were identified at the
      species level. RESULTS: Totally, 19 samples (19/33, 57.6%) and 5 samples (5/33,
      15.2%) were positive for Salmonella with the mean level of 119.4 MPN/100g and
      Campylobacter with the mean level of 58.6 CFU/g, respectively. In terms of
      Salmonella, 166 isolates with 14 serotypes were obtained. Salmonella Enteritidis
      was the most common serovar detected followed by S. Indiana. Serovar diversity
      was very high in all Salmonella isolates and various Salmonella serovars were
      detected in the same chicken carcass. A total of 11 serovar distribution
      spectrums were found and S. Enteritidis in combination with S. Indiana was the
      predominant. CONCLUSION: The retail chicken carcasses in Beijing collected from
      May to July were heavily contaminated by Salmonella with high serovar diversity.

PMID- 25958642
TI  - [Association between joint of heat and noise and metabolic syndrome in steel
      workers].
AB  - OBJECTIVE: To analyze the relationship between joint of heat and noise, and
      metabolic syndrome in a steel rolling factory workers. METHODS: A total of 590
      steel workers were selected as subjects by cluster sampling method from workers
      of a steel factory. They were investigated by face to face way with the unified
      questionnaire which contents included personal information, occupational history,
      personal history, habits and other factors. Furthermore, height, weight, waist
      circumference and blood pressure were measured. Referring to the 2005
      International Diabetes Federation (IDF) issued by the metabolic syndrome (MS)
      worldwide uniform definition combines waist diagnosis MS. A database was built by
      Epidata 3.0 software, and data was analyzed by SPSS 17.0. RESULTS: 571 steel
      workers were from 22 to 60 years, mean age (41.2 -7.9) years old. The prevalence
      of metabolic syndrome in steel workers was 17.9%. The prevalence of metabolic
      syndrome of those who exposed to high temperature was 18.8%, higher than that of
      those who did not expose to high temperature (5.3%), there was a statistically
      significant difference (P < 0.05). The prevalence of metabolic syndrome of those
      who exposed to noise was 20.6%, higher than that of those who did not exposed to
      noise (14.0%) (P < 0.05). After adjusting for the effects of confounding factors,
      the prevalence of MS those who exposed to high temperatures and noise is 1.118
      times as high as that of those who did not exposed to high temperatures and
      noise. CONCLUSIONS: The combined effects of heat and noise is related to the
      increasing prevalence of MS of steel workers.

PMID- 25958641
TI  - [Analysis on 2011 quality control results on aerobic plate count of microbiology
      laboratories in China].
AB  - OBJECTIVE: To test the aerobic plate count examining capability of microbiology
      laboratories, to ensure the accuracy and comparability of quantitative bacteria
      examination results, and to improve the quality of monitoring. METHODS: The 4
      different concentration aerobic plate count piece samples were prepared and noted
      as I, II, III and IV. After homogeneity and stability tests, the samples were
      delivered to monitoring institutions. The results of I, II, III samples were
      logarithmic transformed, and evaluated with Z-score method using the robust
      average and standard deviation. The results of IV samples were evaluated as
      "satisfactory" when reported as < 10 CFU/piece or as "not satisfactory"
      otherwise. Pearson chi2 test was used to analyze the ratio results. RESULTS: 309
      monitoring institutions, which was 99.04% of the total number, reported their
      results. 271 institutions reported a satisfactory result, and the satisfactory
      rate was 87.70%. There was no statistical difference in satisfactory rates of I,
      II and III samples which were 81.52%, 88.30% and 91.40% respectively. The
      satisfactory rate of IV samples was 93.33%. There was no statistical difference
      in satisfactory rates between provincial and municipal CDC. CONCLUSION: The
      quality control program has provided scientific data that the aerobic plate count
      capability of the laboratories meets the requirements of monitoring tasks.

PMID- 25958643
TI  - [Investigation of the arsenic levels in ecosystem aspect in water type of endemic
      arsenicosis area in Datong City].
AB  - OBJECTIVE: To investigate the arsenic levels in endemic arsenism in Datong City,
      Shanxi Province. METHODS: A total of 85 inhabitants from one village in endemic
      arsenism area in Datong City, Shanxi Province were collected as research
      subjects. The People's Republic of China health industry standard for endemic
      arsenism was used to identify and diagnosis the patients. Daily drinking water
      and soil were collected and detected by atomic fluorescence spectrometry. The
      content of vegetables were detected by inductively coupled plasma mass
      spectrometry (ICP-MS). RESULTS: In the study, 85 samples were collected. Arsenic
      concentration in the daily drinking water were 14.41 - 90.34 MUg/L, and the
      median value was 43.88 MUg/L. The arsenic concentration of vegetables were 0.001 
      0.771 mg/kg, and 43.04% of samples, were higher than the maximal permissible
      limit of As in food. The results that the arsenic concentration of vegetables
      constant changes in the leaf vegetables > tubers > fruit vegetables. The health
      risk of intaking arsenic pollution in vegetables up to 71.77%. The arsenic levels
      in village of four directions were not exceeded the Chinese standards.
      CONCLUSIONS: Arsenic concentration in drinking water and vegetables are high in
      waterborn endemic arsenicosis area of Shanxi province. Arsenic in drinking water
      has been considered as a primary cause of arsenism, but direct intake of arsenic
      from vegetables can not be ignored.

PMID- 25958644
TI  - [Study of DHA algal oil compound preparation on improving memory in mice].
AB  - OBJECTIVE: To investigate the effects of docosahexaenoic acid (DHA) algal oil
      compound preparation on improving memory in mice. METHODS: A total of 144 KM mice
      weighed 18 - 22 gram were classified into three groups randomized for the step -
      down test, passive avoidance test and water maze test respectively. For each
      test, we select 48 mice initially, then allocated the mice into 4 groups at
      random, each with 12 mice. According to the recommended dose of DHA algae oil
      soft capsule (600 mg/d) for human, each adult weight calculating on 60 kg meters,
      then we calibrate the dose to 50, 100 and 300 mg/kg BW (the equivalent doses of
      5, 10 and 30 times to human) for three groups, respectively. The dose for
      intragastric injection administration is 10 ml/kg BW DHA algae oil, equivalent
      amount of edible vegetable oil for the control group, once per day for continuous
      30 days. Just after the last lavage, we conduct the step - down test, passive
      avoidance test and water maze test respectively. RESULTS: DHA algal oil compound
      preparation has obvious effect on improving the reappearance ability of passive
      avoidance and the response of the avoiding darkness (P < 0.05). The indicators of
      water maze test were different statistically between DHA algal oil compound
      preparation groups and control group (P < 0.05). CONCLUSION: DHA algal oil
      compound preparation may play an important role in memory improvement in mice.

PMID- 25958645
TI  - [Quantitative investigation of glucuronidated icaritin metabolite in rats].
AB  - OBJECTIVE: To establish an ultra-high performance liquid chromatography-tandem
      mass spectrometry(UHPLC-MS/MS) method for the simultaneous quantification of
      icairitin(ICT) and its major metabolite glucuronidated icaritin (GICT), and
      investigate metabolism of ICT in rats following a single intraperitoneal
      administration. METHODS: ICT, GICT and an internal standard coumestrol (CMT) were
      extracted from rat plasma using acetonitrile and separated on a C18 column using
      a gradient mobile phase of acetonitrile, water, ammonium formate and formic acid.
      In the negative electrospray ionization mode, selected reaction monitoring of the
      precursor-product ion transitions of m/z 367.1 --> 297.1 for ICT, 543.3 --> 367.1
      for GICT and 267.0 - 211.1 for CMT was used for the quantification. Plasma was
      collected for the determination of ICT and GICT after rats were intraperitoneally
      administered with ICT at a single dose of 10 mg/kg. RESULTS: The calibration
      curves were linear over the concentration range of 0.2 - 20 ng/ml for ICT and 2 
      200 ng/ml for GICT with the respective lower limit of quantification at 0.2 and 2
      ng/ml. The intra- and inter-day accuracy values fell in the range of 95.1 -
      103.7%, and precisions were within 10.3%. Recovery and matrix effect were 89.1 -
      92.4% and 93.2 - 104.2%, respectively. CONCLUSION: The UHPLC-MS/MS method was
      specific and accurate, suitable for the metabolism study of ICT. ICT was rapidly
      metabolized to GICT in rats.

PMID- 25958646
TI  - [Preparation of characterization of complete antigen of T-2 toxin and
      deoxynivalenol].
AB  - OBJECTIVE: To synthesize the complete antigen of T-2 toxin and deoxynivalenol
      (DON), respectively. METHODS: T-2 toxin and DON were coupled with carrier protein
      after derivation with succinic anhydride. Molecular weights of the conjugates and
      carrier protein were detected by MALDI-TOF. And the performance of complete
      antigens were further validated by chequerboard titration using commercial
      immunoassay kits for T-2 toxin and DON. RESULTS: The molecular weights of T-2,
      DON conjugates and BSA were 67641.6, 66680.4 and 66297.7, respectively.
      CONCLUSION: The preparation of complete antigen of T-2 and DON will greatly
      facilitated antibody production and immunoassay development.

PMID- 25958647
TI  - [Determination of phthalic acid esters plasticizer in food simulants by gas
      chromatography-mass spectrometry isotope dilution method].
AB  - OBJECTIVE: The isotope dilution method for determination of 18 phthalic acid
      esters(PAEs) plasticizer in four kinds of food simulants were developed. METHODS:
      18 PAEs were extracted by hexane in water, 3% (W/V) acetic acid and 20% ethanol
      of food stmulant. The 95% ethanol of food simulant was diluted to 20% ethanol by
      water and then was extracted by hexane. RESULTS: The linear range of DINP and
      DIDP were 0.2 - 5.0 mg/L meanwhile the DMEP, DEEP and DBEP were 0.02 -2.0 mg/L,
      the other 13 PAEs were 0.005 -2.0 mg/L, the relative coefficients were greater
      more than 0.9991 by internal standard calibration. The limit of detection of
      16PAEs were 0.1 - 6.7 MUg/L, DIDP and DINP were 200.0 MUg/L. The average
      recoveries were from 85.3% to 115.0% with RSD less than 10%. CONCLUSIONS:
      Compared with the previous national standard method, the detection series of
      phthalic acid esters were expanded. The stability of the test results were solved
      in simulant 95% ethanol. The method is simple and repeatable by isotope dilution
      statutory quantitatively.

PMID- 25958648
TI  - [Effect of cadmium chloride on immigration of mouse neural stem cell].
AB  - OBJECTIVE: To investigate the effects of cadmium chloride on cytoactive and
      immigration of mouse neural stem cell (mNSC). METHODS: MTT assay was used to
      detect cytoactive at 24 hours. The immigration of mNSC was determined by
      immunofluorescence staining. RESULTS: Compared with control, CdCl2 treatment at
      10.0 MUmol/L for 24 h resulted in a decrease in cellular viability (70.08 +/-
      6.21)% (P < 0.05). Compared with control, Aa/Ab and Dm/Db display decreasing
      tendency in a dose-dependent manner (r(s Aa/Ab) = - 0.90, gamma(s Dm/Db) = -
      0.90, P < 0.05) after CdCl2 treatment at 0.1 - 10.0 MUmol/L for 24 h. CONCLUSION:
      Cadmium chloride treatment inhibits immigration of mNSC, and shows negative
      effect on cell viability. Meanwhile, the effect of cadmium chloride on
      immigration is more obvious than cell viability at the same concentration for
      same treatment time.

PMID- 25958649
TI  - Near-death experiences--I hope you are comfortable with them by now!

PMID- 25958650
TI  - Near-death experiences--Neuroscience perspectives on near-death experiences.

PMID- 25958651
TI  - Talk to me.

PMID- 25958652
TI  - The measles outbreak coming near you.

PMID- 25958653
TI  - What you don't know about vaccines can hurt you.
AB  - As physicians, we've all learned in detail about the science behind vaccinations,
      but I suspect few of us have been taught about the history of vaccinations. Sure,
      we all know that Dr. Jonas Salk developed the poliovirus vaccine, but I wasn't
      aware that he inoculated himself, his wife, and his three children with his then
      experimental vaccine. When our editorial committee decided to focus on
      vaccinations as our theme for this month's Greene County Medical Society's
      Journal, I perused the internet for interesting topics. I came across a
      fascinating website, historyofvaccines.org; this website is a project of the
      College of Physicians of Philadelphia, touted as being the oldest professional
      medical organization in the United States. I credit the majority of the
      information in this article to the above website and the rest to the National
      Institutes of Health (nih.gov) website; I trust that the information is valid and
      true, based on the agencies behind these websites. Below are some interesting
      tidbits about vaccine preventable diseases that I found noteworthy to pass on to
      our readers.

PMID- 25958654
TI  - Reading Missouri medicine for the medicine.

PMID- 25958655
TI  - Food, mood, and brain health: implications for the modern clinician.
AB  - Improved, innovative strategies are needed for the prevention and promotion of
      recovery from mental illness as these disorders leading cause of disability
      worldwide. This article will review the evidence linking dietary pattern to brain
      based illnesses and provide an overview of the mechanisms that underlie the
      association between brain health and the food we eat. Considerations for dietary
      intervention will be discussed including encouraging a shift towards a
      traditional or whole foods dietary pattern.

PMID- 25958656
TI  - Childhood myopia: epidemiology, risk factors, and prevention.
AB  - Our understanding of the dynamic interaction between the eye's growth and its
      ability to adapt to maintain vision has shown that childhood myopia is a
      significant prediction of progressive myopia and the potentially severe ocular
      comorbidities associated with it. It is important for us to better understand
      this process and its risk factors in order to better develop a prevention and
      treatment strategy. This article will discuss the epidemiology, risk factors and
      current therapeutic regimens for reducing myopic progression.

PMID- 25958657
TI  - Treating the elite athlete: anti-doping information for the health professional.
AB  - Physicians and health professionals are a vital component in preserving the
      integrity of competition and the core principles of true sport. When treating an
      athlete, health professionals need to be cognizant of the anti-doping rules of
      the relevant sport organization. This review aims to provide an overview of the
      World Anti-Doping Agency Prohibited List, Therapeutic Use Exemptions, roles and
      responsibilities of the health professional, as well as provide resources that
      will guide their work with athletes.

PMID- 25958658
TI  - Telemedicine and beyond.
AB  - There is a resurgence of interest in telemedicine fueled by technology
      advancements and impending changes in reimbursement. Understanding various types
      of telemedicine helps separate hype from fact. This paper discusses the various
      forms of telemedicine; reviews telemedicine policy and regulatory status with
      emphasis in our [Missouri and Kansas] region; lists legislative, interstate
      licensing and reimbursement initiatives; and discusses future telemedicine trends
      with special attention to mobile devices.

PMID- 25958659
TI  - Updates on management of anoxic brain injury after cardiac arrest.
AB  - Brain injury is a leading cause of mortality and morbidity among cardiac arrest
      survivors. Management of these patients in the acute phase is challenging as is
      predicting their outcomes especially with the application of hypothermia.
      Therapeutic hypothermia has been proven beneficial but target temperature,
      timing, and duration that produce the best outcome are unclear and the subject of
      ongoing research. We review the recent advances in therapy and update the
      guidelines for management of these patients.

PMID- 25958660
TI  - [Annual review of capillary electrophoresis technology in 2014].
AB  - This paper reviews the capillary electrophoresis (CE) in 2014. Five international
      and two national conferences are included and the important reports are
      introduced briefly. The literatures from ISI Web of Science published in 2014
      (Jan. 1st to Dec. 15th) are classified and introduced based on the biology and
      medicine applications, the use of detectors as well as the important analytical
      chemical journals. In the end, CE developments in 2012-2014 are reviewed and
      compared.

PMID- 25958661
TI  - [Identifying phosphopeptide by searching a site annotated protein database].
AB  - Phosphoproteome analysis is one of the important research fields in proteomics.
      In shotgun proteomics, phosphopeptides could be identified directly by setting
      phosphorylation as variable modifications in database search. However, search
      space increases significantly when variable modifications are set in post
      translation modifications (PTMs) analysis, which will decrease the identification
      sensitivity. Because setting a variable modification on a specific type of amino
      acid residue means all of this amino acid residues in the database might be
      modified, which is not consistent with actual conditions. Phosphorylation and
      dephosphorylation are regulated by protein kinases and phosphatases, which can
      only occur on particular substrates. Therefore only residues within specific
      sequence are potential sites which may be modified. To address this issue, we
      extracted the characteristic sequence from the identified phosphorylation sites
      and created an annotated database containing phosphorylation site information,
      which allowed the searching engine to set variable modifications only on the
      serine, threonine and tyrosine residues that were identified to be phosphorylated
      previously. In this database only annotated serine, threonine and tyrosine can be
      modified. This strategy significantly reduced the search space. The performance
      of this new database searching strategy was evaluated by searching different
      types of data with Mascot, and higher sensitivity for phosphopeptide
      identification was achieved with high reliability.

PMID- 25958662
TI  - [Simultaneous determination of six components in hair dyes by ultra performance
      liquid chromatography-tandem mass spectrometry].
AB  - A sensitive method was developed for the simultaneous determination of six
      components which included 4, 4'-diaminodiphenylamine sulfate hydrate and 2,4
      diaminophenol sulfate, etc. in hair dyes by ultra performance liquid
      chromatography-tandem mass spectrometry (UPLC-MS/MS). After extracted by water
      through ultrasonic extraction, the samples were analyzed by UPLC-MS/MS. The
      separation was performed on a Waters BEH-C18 column (100 mmx 2.1 mm, 1.7 microm)
      with gradient elution of 10 mmol/L ammonium acetate and acetonitrile. The
      electrospray ionization (ESI) source in positive ion mode was used for the
      analysis of the six components in the multiple reaction monitoring (MRM) mode.
      The results showed good linear relationships with all the correlation
      coefficients (R2) more than 0.99. The limits of detection (LODs, S/N=3) for the
      six components were in the range of 0.26-4.6 mg/kg. The average recoveries of the
      six components in the spiked samples were in the range of 83.0%-92.2% with the
      relative standard deviations (RSDs, n=6) of 5.4%-11.2%. The precision, accuracy,
      mean recoveries and the matrix effects satisfied the requirements of cosmetic
      sample measurement. The proposed method has been applied to the determination of
      six dyes in actual samples. This method is simple, accurate and effective for the
      simultaneous determination of the six components in hair dyes.

PMID- 25958663
TI  - [An ultra-high-pressure liquid chromatography/linear ion trap-Orbitrap mass
      spectrometry method coupled with a diagnostic fragment ions-searching-based
      strategy for rapid identification and characterization of chemical components in
      Polygonum cuspidatum].
AB  - A method for qualitative analysis of constituents in Polygonum cuspidatum by
      ultra-high-pressure liquid chromatography coupled with linear ion trap-Orbitrap
      mass spectrometry (UHPLC-LTQ-Orbitrap MS) has been established. The methanol
      extract of Polygonum cuspidatumrn was separated on a Waters UPLC C18 column using
      acetonitrile-water (containing formic acid) eluting system and detected by LTQ
      Orbitrap hybrid mass spectrometer in negative mode. The targeted components were
      further fragmented in LTQ and high accuracy data were acquired by Orbitrap MS.
      The summarized fragmentation pathways of typical reference components and a
      diagnostic fragment ions-searching-based strategy were used for detection and
      identification of the main phenolic components in Polygonum cuspidatum. Other
      clues such as nitrogen rule, even electron rule, degree of unsaturation rule and
      isotopic peak data were included for the structural elucidation as well. The
      whole analytical procedure was within 10 min and more than 30 components were
      identified or tentatively identified. This method is helpful for further
      phytochemical research and quality control on Polygonum cuspidatum and related
      preparations.

PMID- 25958664
TI  - Polyamide as an efficient sorbent for simultaneous interface-free determination
      of three Sudan dyes in saffron and urine using high-performance liquid
      chromatography-ultra violet detection.
AB  - With polyamide (PA) as an efficient sorbent for solid phase extraction (SPE) of
      Sudan dyes II, III and Red 7B from saffron and urine, their determination by HPLC
      was performed. The optimum conditions for SPE were achieved using 7 mL
      methanol/water (1:9, v/v, pH 7) as the washing solvent and 3 mL tetrahydrofuran
      for elution. Good clean-up and high (above 90%) recoveries were observed for all
      the analytes. The optimized mobile phase composition for HPLC analysis of these
      compounds was methanol-water (70:30, v/v). The SPE parameters, such as the
      maximum loading capacity and breakthrough volume, were also determined for each
      analyte. The limits of detection (LODs), limits of quantification (LOQs), linear
      ranges and recoveries for the analytes were 4.6-6.6 microg/L, 13.0-19.8 microg/L,
      13.0-5000 microg/L (r2>0.99) and 92.5%-113.4%, respectively. The precisions
      (RSDs) of the overall analytical procedure, estimated by five replicate
      measurements for Sudan II, III and Red 7B in saffron and urine samples were 2.3%,
      1.8% and 3.6%, respectively. The developed method is simple and successful in the
      application to the determination of Sudan dyes in saffron and urine samples with
      HPLC coupled with UV detection.

PMID- 25958665
TI  - [Determination of seven biothiols in rice by high performance liquid
      chromatography-fluorescence detection with pre-column derivatization].
AB  - A high performance liquid chromatographic method with fluorescence detection and
      precolumn derivatization (HPLC-FLD) has been developed for the determination of
      seven biothiols including Cys, GSH, and phytochelatins (PCs: PC2, PC3, PC4, PC5
      and PC6) in rice. The samples were ultrasonically extracted with 0.1%
      trifluoroacetic acid (TFA) containing 6. 3 mmol/L diethylenetriaminepentaacetic
      acid (DTPA), and then the seven biothiols were derivatized with monobromobimane
      (mBrB) as derivatization agent in 4-(2-hydroxyethyl)-1-piperazine propanesulfonic
      acid (HEPPS) buffer solution (pH 8.0). The separation was performed on an Agilent
      Eclipse Plus C18 column (50 mm x 4.6 mm, 5 microm) with gradient elution of 0.1%
      TFA solution (the pH value was adjusted to 2.5 with hydrochloric acid) and
      acetonitrile as mobile phases at a flow rate of 0.8 mL/min. The detection was
      performed at 380 nm for excitation and 470 nm for emission. The calibration
      curves of the seven biothiols showed good linearity in the concentration range of
      0.7-100.0 mg/L with the correlation coefficients (r2) > or = 0.9991. The limits
      of detection were 0.03-0.20 mg/L. The recoveries of standard addition were in the
      range of 89.26%-99.42% with the relative standard deviations (RSDs, n = 6) of
      2.05%-5.87%. The method is sensitive, accurate, reproducible and suitable for the
      simultaneous determination of Cys, GSH, PC2, PC3, PC4, PC5 and PC6 in rice.

PMID- 25958666
TI  - [Determination of hexachlorocyclohexane and dichlorodiphenyltrichloroethen
      residues in honey by gas chromatography-mass spectrometry combined with
      dispersive liquid-liquid microextraction].
AB  - A gas chromatography-mass spectrometry (GC-MS) method for the determination of
      hexachlorocyclohexane (BHC) and dichlorodiphenyltrichloroethane (DDT) residues in
      honey was developed using dispersive liquid-liquid microextraction (DLLME) as
      sample preparation method. The samples were extracted with chloroform, and
      concentrated into chloroform by vortex and centrifuging. The analytes were
      analyzed by GC-MS. The factors affecting the extraction efficiency were
      investigated, such as the type and volume of extraction and dispersive solvent,
      extraction time, etc. The matrix effects and method performance were evaluated at
      the same time. The results indicated that all the eight BHC and DDT pesticides
      displayed the enhancement of signals due to the matrix effects. The calibration
      curves were linear in the range of 2-500 microg/L and the correlation
      coefficients were 0.991-0.998 for the eight BHC and DDT pesticides. The
      enrichment factors (EF) were 74-96 for the eight pesticides. The recoveries of
      the eight BHC and DDT pesticides at three spiked levels of 20, 50 and 100
      microg/kg were 61.0%-100.1%, while the RSDs were 2.2%-19.5%. The limits of
      quantification for the eight pesticides were 20 microg/kg, and the limits of
      detection were 1.0 ng. The developed method is easy, quick and with high
      performance. It is applicable for the determination of BHC and DDT residues in
      honey.

PMID- 25958668
TI  - [Feasibility investigation of hydrogen instead of helium as carrier gas in the
      determination of five organophosphorus pesticides by gas chromatography-mass
      spectrometry].
AB  - Helium is almost the only choosable carrier gas used in gas chromatography-mass
      spectrometry (GC-MS). A mixed standard solution of five organophosphorus
      pesticides was analyzed by using GC-MS, and hydrogen or helium as carrier gas, so
      as to study the feasibility of hydrogen instead of helium as carrier gas for the
      determination of organophosphorus pesticides. Combining a mass spectrum database
      built by ourselves, the results were deconvolved and identified by Automated Mass
      Spectral Deconvolution & Identification System (AMDIS32), a software belonging to
      the workstation of the instrument. Then, the statistical software, IBM SPSS
      Statistics 19.0 was used for the clustering analysis of the data. The results
      indicated that when hydrogen was used as carrier gas, the peaks of the pesticides
      detected were slightly earlier than those when helium used as carrier gas, but
      the resolutions of the chromatographic peaks were lower, and the fraction good
      indices (Frac. Good) were lower, too. When hydrogen was used as carrier gas, the
      signals of the pesticides were unstable, the measuring accuracies of the
      pesticides were reduced too, and even more, some compounds were undetectable.
      Therefore, considering the measuring accuracy, the signal stability, and the
      safety, etc., hydrogen should be cautiously used as carrier gas in the
      determination of organophosphorus pesticides by GC-MS.

PMID- 25958667
TI  - [Pyrolysates of novel latent fragrant compound 3,6-dimethyl-2,5
      pyrazinedicarboxylic acid menthol ester].
AB  - In order to develop a new tobacco flavor released at high-temperature, the novel
      latent fragrant compound 3,6-dimethyl-2,5-pyrazinedicarboxylic acid menthol ester
      (DPAME) was synthesized by esterification using 2,3,5,6-tetramethylpyrazine and
      menthol as raw materials. In air atmosphere, the pyrolysis behavior of DPAME was
      investigated using an on-line pyrolysis-gas chromatography-mass spectrometry (Py
      GC-MS) method at three temperature levels of 300, 600 and 900 degrees C,
      separately. The pyrolysis products were directly introduced into GC-MS and were
      qualitatively and semi-quantitatively analyzed. The results showed that a variety
      of aroma compounds of aldehydes, 3-p-menthene and menthol were released and
      identified at 300 degrees C. While at 600 degrees C and 900 degrees C, flavor
      alkene class, the alkyl pyrazines, menthol and 3-p-menthene were generated. And
      the types and relative amounts of pyrazines were significantly increased, at
      these two temperatures. Combined the analytical results of DPAME pyrolysates and
      the results of sensory evaluation of the cigarette, the possible pyrolysis
      mechanism was preliminarily speculated. The Py-GC-MS technique for the study of
      the pyrolysis products of DPAME was convenient and rapid. The investigation
      provided a reliable theoretical foundation for the perfume reinforcement
      technology in tobacco products, contributing to the development of cigarette
      products with better aroma and taste. This method is an accurate and quick way to
      study the pyrolysis products of latent fragrant substance.

PMID- 25958669
TI  - [Determination of the thermodynamic parameters of ionic liquid 1-hexyl-3
      methylimidazolium tetrafluoroborate by inverse gas chromatography].
AB  - Inverse gas chromatography (IGC) was used to characterize the thermodynamic
      properties of ionic liquid (IL) 1-hexyl-3-methylimidazolium tetrafluoroborate
      ([HMIM] BF4) in the temperature range from 343.15 K to 373. 15 K. A series of
      solvents with different chemical natures were used to determine the [HMIM] BF4
      solvent interactions. The thermodynamic parameters including Flory-Huggins
      interaction parameter, partial molar heats of sorption, mixing and evaporation as
      well as the activity coefficient at infinite dilution were obtained to judge the
      interactions between [HMIM]BF4 and the selected solvents. In addition, the
      solubility parameters of [HMIM] BF4 at different temperatures were determined.
      The results showed that among the selected solvents, n-C6, n-C7, n-C8, n-C9,
      diethyl ether, tetrahydrofuran, benzene and cyclohexane were poor solvents for
      [HMIM] BF4, while toluene, m-xylene, methanol, ethanol, dichloromethane,
      tetrachloromethane, chloroform, acetone, ethyl acetate and methyl acetate were
      the favorite ones. The solubility parameter of [HMIM]BF4 at room temperature
      (298.15 K) was 23.70 (J x cm(-3)(0.5), which was obtained by the linear
      extrapolation method. The experiment proved that IGC is a simple and accurate
      method to obtain the thermodynamic properties of ionic liquids. The obtained
      thermodynamic parameters revealed the strength of the interactions between the
      selected solvents and the ionic liquid, which could be used as a reference to the
      further applications of the ionic liquid.

PMID- 25958670
TI  - [Determination of wilforine in honey using solid phase extraction purification
      and ultra performance liquid chromatography-tanden mas spectrometry].
AB  - A method based on solid phase extraction and ultra performance liquid
      chromatography coupled with tandem mass spectrometry (SPE-UPLC-MS/MS) has been
      proposed for the determination of wilforine residue in honey. After the sample
      was dissolved with water, concentrated and purified by an HLB solid phase
      extraction cartridge, the UPLC separation was performed on a Hypersil GOLD C18
      column (50 mm x 2.1 mm, 1.9 microm) utilizing a gradient elution program of
      methanol (containing 0.15% formic acid) and water as mobile phases at a flow rate
      of 0. 25 mL/min. The determination was carried out with electrospray ion source
      in the positive mode (ESI) and multiple reaction monitoring (MRM) mode. The mass
      concentration of wilforine in the range of 0.01-2 microg/L was linearly
      correlated with the peak area, and the correlation coefficients was greater than
      0.998. The limit of quantification (S/N>10) for wilforine was 0.01 microg/kg. The
      recoveries were 76.1% to 96.2% in the spiked levels of 0.01, 0.05 and 0.5
      microg/kg with the relative standard deviations (RSD, n=6) lower than 10%. The
      results indicate that the method is rapid, sensitive and accurate, and can be
      applied for the qualitative and quantitative analysis of wilforine in honey.

PMID- 25958671
TI  - [Determination of di (hydrogenated tallow alkyl) dimethyl ammonium compounds in
      textile auxiliaries by ultra-high performance liquid chromatography-tandem mass
      spectrometry].
AB  - A method has been developed for the determination of di (hydrogenated tallow
      alkyl) dimethyl ammonium compounds (DHTDMAC) in textile auxiliaries by ultra-high
      performance liquid chromatography-tandem mass spectrometry. (UPLC-MS/MS). The
      samples were extracted and diluted with acidified methanol by 5% (v/v) formic
      acid under ultrasonic assistance. The separation was performed on an Eclipse Plus
      C18 column (50 mm x 2.1 mm, 1.8 microm) using 0.1% (v/v) formic acid solution and
      methanol as the mobile phases. Identification and quantification were achieved by
      UPLC-MS/MS with electrospray ionization (ESI) source in positive ion mode and
      multiple reaction monitoring (MRM) mode. The results indicated that the
      calibration curve of DHTDMAC showed good linear relationship between peak area
      and mass concentration in the range of 10-280 microg/L with the correlation
      coefficient (r2) of 0.9991. The limit of detection (LOD, S/N=3) and the limit of
      quantification (LOQ, S/N= 10) of this method were 3 mg/kg and 10 mg/kg,
      respectively. The average recoveries from three typical textile auxiliary
      matrices including dispersant, antistatic agent and fabric softener, at three
      spiked levels were in the range of 97.2%-108.3% with the relative standard
      deviations (RSDs) of 1.5%-4.6%. The method is sensitive, accurate, simple and
      effective for the analysis of DHTDMAC in textile auxiliaries.

PMID- 25958672
TI  - [Determination of three isothiazolinone biocides in water-borne adhesives by high
      performance liquid chromatography].
AB  - A rapid high performance liquid chromatography (HPLC) method was developed for
      the quantitative analysis of three isothiazolinone biocides (2-methyl-4
      isothiazolin-3-one (MI), 5-chloro-2-methyl-4-isothiazolin-3-one (CMI) and 1, 2
      benzylisothiazolin-3-one (BIT)) in water-borne adhesives. The sample was
      extracted with methanol-water (1:1, v/v), and purified by centrifugation and
      filtration. The isothiazolones were separated on a C18 column with methanol-water
      as mobile phases under gradient elution and detected with a diode array detector
      (DAD). The pretreatment factors such as extraction solvent, extraction method,
      dilution ratio, extraction time were optimized. Under the optimized conditions,
      the targets had good linearities (r2H > or = 0.9992) in the range of 0.25-10.0
      mg/L. The recoveries were between 92% and 103% with the relative standard
      deviations not more than 4%. The limits of detection (LODs) were between 0.43
      mg/kg and 1.14 mg/kg. The limits of quantification (LOQs) were between 1.44 mg/kg
      and 3.81 mg/kg. The results showed that the method can achieve the purpose of
      quantitative detection. The analyses of real samples verified the reliability of
      this method.

PMID- 25958673
TI  - [Determination of urea in canned foods by high performance liquid chromatography
      fluorescence detection coupled with precolumn derivatization].
AB  - A method for the determination of urea residue in canned foods by high
      performance liquid chromatography-fluorescence detection (HPLC-FLD) coupled with
      precolumn derivatization was established. The sample (5.0 g), including canned
      edible fungi, fruit, vegetable, fish, and meat was extracted with 20 mL 1% (v/v)
      acetic acid solution. The extract was centrifuged, filtrated, and then
      derivatized with xanthydrol. The analysis was completed with HPLC-FLD. A good
      linear relationship was obtained in the range of 0.1-500 mg/L with the
      correlation coefficients more than 0.9995. The average recoveries of urea spiked
      at 0.001-30 g/kg levels in five kinds of canned foods ranged from 80.2% to 109.7%
      with the RSDs of 2.05%-6.53%. The limit of detection (LOD) was 0.5 mg/kg, and the
      limit of quantitation (LOQ) was 1.0 mg/kg. The proposed procedure was then
      applied to the analysis of 168 real samples collected from Xiamen, Fujian
      Province, China. The existence of urea was found in three pork cans with contents
      of 10.6, 62.1 and 2.6 mg/kg, respectively. The method is stable, reliable, simple
      and suitable for the determination of urea in canned foods, and has great
      potential for routine analysis in foodstuffs.

PMID- 25958675
TI  - [Determination of low-carbon alcohols, aldehydes and ketones in aqueous products
      of Fischer-Tropsch synthesis by gas chromatography].
AB  - A method for the determination of low-carbon (C1-C8) alcohols, aldehydes and
      ketones in aqueous products of Fischer-Tropsch synthesis was developed by gas
      chromatography. It included the optimization of separation conditions, the
      precision and accuracy of determination, and the use of correction factors of the
      analytes to ethanol for quantification. The aqueous products showed that the
      correlation coefficients for ethanol in different content ranges were above 0.99,
      which means it had good linear correlations. The spiked recoveries in the aqueous
      samples of Fischer-Tropsch synthesis were from 93.4% to 109.6%. The accuracy of
      the method can satisfy the requirement for the analysis of the aqueous samples of
      Fischer-Tropsch synthesis. The results showed that the total mass fractions of
      the major low-carbon alcohols, aldehydes, ketones in aqueous products of Fischer
      Tropsch synthesis were about 3%-12%, and the contents of ethanol were the highest
      (about 1.7%-7.3%). The largest share of the total proportion was n-alcohols,
      followed by isomeric alcohols, aldehydes and ketones were the lowest. This method
      is simple, fast, and has great significance for the analysis of important
      components in aqueous products of Fischer-Tropsch synthesis.

PMID- 25958674
TI  - [Isolation of chemical constituents from Ziziphora clinopodioides Lam. with
      recycling preparative high performance liquid chromatography].
AB  - The combination of alternate recycling and direct recycling preparative liquid
      chromatography method was developed for the isolation of chemical constituents
      from Ziziphora clinopodioides Lam. The crude extract was obtained from Ziziphora
      clinopodioides Lam. by solvent extraction, column chromatography and reversed
      phase (RP) flash chromatography. All the separations were performed with methanol
      and water as mobile phases and the developed recycling preparative method was
      used with twin RP columns switched by a two-position ten-way valve for the
      separation. The mobile phase was recycled in close loop with a two-position six
      way valve. The fraction I and fraction II from reversed-phase flash
      chromatography were selected for the demonstration of separation power of the
      proposed protocol, and five compounds were obtained from Ziziphora clinopodioides
      Lam. The isolated five compounds were identified as pinocembrin-7-O-rutinoside,
      pinocembrin-7-O-rutinoside, acacetin-7-O-rutinoside, picein and protocatechuic
      acid with nuclear magnetic resonance (NMR). The experimental results showed that
      the developed preparation method exhibited higher separation efficiency with less
      mobile phase used than the reported methods, and could be expected as an
      effective method for the separation of complex natural products, especially the
      compounds with similar structures.

PMID- 25958676
TI  - [Surface properties of ZuMgAl hydrotalcite-like compounds by inverse gas
      chromatography].
AB  - The structure of ZnMgAl hydrotalcite-like compounds (ZnMgAl-HTLC) prepared by
      hydrothermal synthesis was studied by X-ray diffraction (XRD). With a series of
      polar and nonpolar molecules as probes, inverse gas chromatography (IGC) was used
      to measure the surface properties of ZnMgAl-HTLC. It was found that the XRD
      pattern of ZnMgAl-HTLC was narrow, sharp and high. The results showed that ZnMgAl
      HTLC with a higher purity was obtained by hydrothermal synthesis. The surface
      adsorption free energy was less than zero. The surface dispersive free energy was
      6.02 mJ/m2. The acid-base interaction free energy was 5.33 kJ/mol. The adsorption
      enthalpy was 43.6 kJ/mol, and the adsorption entropy was 0.15 kJ/mol. The IGC
      method is significant in the study of the surface properties of ZnMgAl-HTLC.

PMID- 25958677
TI  - [The family Thermoactinomycetaceae--a review].
AB  - Thermoactinomycetaceae is a new and old prokaryotic group. The present taxonomic
      status is: Domain Bacteria, Phylum Firmicutes, Class Bacilli, Order Bacillales,
      Family Thermoactinomycetaceae. Study on this family is going on more than a
      century. Until now, this family comprises of 14 genera and 25 species. Members of
      the family Thermoactinomycetaceae are widely distributed in the terrestrial hot
      springs, high-temperature Daqu (a starter culture for Chinese alcohol
      fermentation), compost, straw, bagasse and other places of high temperature, and
      marine sediments. The drug-resistance spores can survive in soil, water for long
      time. They also have great potential in both industrial and drug development, So
      they got a wide attention by scholars. This paper reviews the research progress
      of taxonomical studies and ecological diversity of the family
      Thermoactinomycetaceae, also introduces their potential applications in drug
      development and industrial production.

PMID- 25958678
TI  - [Molecular genetic makers for Vibrio parahaemolyticus--a review].
AB  - Vibrio parahaemolyticus is an important foodborne pathogen, of which the 03:K6
      serotype caused many outbreaks in different countries since 1996. Based on the 10
      years data (1992-2001) from China, gastroenteritis caused by Vibrio
      parahaemolyticus accounted for 31.1% of foodborne disease outbreaks that were
      resulted from microorganisms. Most environmental strains of Vibrio
      parahaemolyticus are non-pathogenic strains. However, clinical strains can
      producethermostable direct hemolysin (TDH), TDH-related hemolysin, and other
      virulence factors. Here we reviewed three commonly used molecular markers for
      Vibrio parahaemolyticus, including species-specific genes, the virulence genes
      and pandemic group-specific genes, so that to provide references for the rapid
      detection of Vibrio parahaemolyticus and the identification of its pathogenic
      factor.

PMID- 25958679
TI  - Induction, separation and identification of haploid strains from industrial
      brewer's yeast.
AB  - OBJECTIVE: Lager brewing yeasts (Saccharomyces pastorianus), the natural hybrids
      of S. cerevisiae and S. eubayanus, are usually heterothallic polyploidy or
      aneuploidy. Their intricate ploidy is a great challenge to genetic studies and
      strain improvement. Haploid breeding is an effective method to overcome these
      difficulties. Also, haploid strains play an important role in scientific research
      and breeding. However, lager brewing yeasts only divide asexually and hardly bear
      spores under normal conditions, so it is very difficult to get haploid strains
      from them. In this study, we established comprehensive methods to induce,
      separate and identify haploid strains of industrial brewer's yeast. METHODS:
      First, we selected efficient sporulation medium to induce the sporulation of an
      industrial brewer's yeast strain G-03, and ther isolated spores from vegetative
      cells and formed colonies on YPD plates. After that, flow cytometry was used to
      determine the ploidy types of the pre-judged haploid candidates. Ultimately, we
      analyzed the genotypes of the segregants by PCR reaction and mating test in order
      to get precise results. RESULTS: Using this protocol, we obtained 26 yeast
      segregants by spore isolation, and 4 of them pre-judged as haploid candidates
      were finally confirmed as haploid by flow cytometric analysis. Two of them were
      MATa and others were MATalpha. By scanning electron microscope (SEM), the cells
      of 4 haploid segregants showed similar morphology to each other but had obvious
      differences compared with the parent strain. Pseudohyphal growth occurred in
      parent cells after long-period cultivation but none was found in haploid
      segregants. CONCLUSION: Sporulation of industrial brewer's yeast and germination
      of their spores was difficult but not impossible. Nevertheless, the screening and
      identification of haploid segregants were more challenging.

PMID- 25958680
TI  - Screening of endophytic fungi with anti-phytopathogen activities from Heptacodium
      miconioides.
AB  - OBJECTIVE: To find anti-phytopathogen compounds from endophytic fungi associated
      with the endangered species Heptacodium miconioides. METHODS: Fungi from H.
      miconioides with antifungal activities were isolated according to the plate
      growth inhibition method. The fungus with preferable antifungal activities was
      identified by morphological identification and 5. 8S rRNA sequence analysis. The
      bioactive metabolites were isolated and purified by chromatographic methods; the
      structures were determined by spectroscopic analysis. RESULTS: Alternaria solani
      QZH 10 showed better antifungal activity against Rhizoctorzia solani and Valsa
      mali with the inhibition rates of 89.1% and 67.9%, respectively. The ethyl
      acetate crude extract of QZH 10 had strong antifungal activity against
      Magnaporthe oryzae with the rate of 100. 0% under the concentration of 100
      MUg/mL. Two antifungal metabolites altersolanol A and 6-O-methylalaternin were
      isolated and determined from QZH 10. Altersolanol A possessed strong activity
      against M. oryzae with the inhibition rate of more than 85%, 6-O-methylalaternin
      had the mightily activity against V. mali with the inhibition rate of 100.0%
      under the concentration of 100 MUg/mL. CONCLUSION: Altersolanol A and 6-O
      methylalaternin are potential fungicides originated from microorganisms.

PMID- 25958681
TI  - [Characterization of solute-binding protein XynE of the xylooligosaccharide
      transporter from Bacillus sp. N16-5].
AB  - The alkaliphilichemicellulolytic bacterium Bacillus sp. N16-5 was isolated from
      Lake Wudunao in Inner Mongolia. It has a broad substrate spectrum and exhibits a
      capacity to utilize complex carbohydrates such as galactomannan, xylan and
      pectin. Previous transcriptional analysis of differential carbohydrate
      utilization by Bacillus sp. N16-5 has identified a putative gene cluster related
      to xylan utilization. It contains a putative xylo-oligosaccharide ATP- binding
      cassette (ABC) transporter encoded by xynEFG gene cluster. OBJECTIVE: xynE gene
      is predicted to encode an extracellular solute-binding protein of the ABC
      transporter. Here, the physiological roles of xynE on the xylan utilization was
      investigated by gene deletion. METHODS: We obtained the xynE deficient strain N16
      5 (DeltaxynE) through homologous recombination using a temperature sensitive
      shuttle vector pNNB194. The effects of xynE on xylan utilization by N16-5 were
      detected by comparing the growth profiles on xylan of the wild type and mutant
      strains as well as the variation of reducing sugars concentration in the medium
      during cultivation. We further verified the phenotype by constructing the
      complementary strain. Moreover, the substrate specificity of XynE was illustrated
      by the HPLC analysis results of the xylan medium components, which was
      supplemented with the growth profiles of the wild type strain and N16-5
      (DeltaxynE) strain on xylose. RESULTS: Compared with the wild type strain, strain
      N16-5 (DeltaxynE) had a delayed exponential phase, obtained a lower maximum
      optical intensity OD600 value, and presented the accumulation and depletion of
      reducing sugars during cultivation. The complementary strain retrieved the
      phenotype of wild type strain, and grown slightly better than it. HPLC analysis
      showed that N16-5 ( DeltaxynE) strain degraded the xylan substrates more slowly
      than wild type, xylo- oligosaccharides like xylotetraose, xylotriose and
      xylobiose began to accumulate after 16 h cultivation. Moreover it still maitained
      a large number of the degradation product xylobiose in the medium after 60 h.
      When cultured in xylose medium, strain N16-5 (DeltaxynE) performed similar growth
      profile with the wild type strain. CONCLUSION: XynE played an important role in
      rapidly and effectively utilizing xylan in Bacillus sp. N16-5 and specifically
      related with xylo-oligosaccharide uptake.

PMID- 25958682
TI  - [Individual catalytic activity of two functional domains of bovicin HJ50 synthase
      BovM].
AB  - OBJECTIVE: To reconstitute the in vitro catalytic activity of the individual
      dehydratase or cyclase domain of bifunctional bovicin HJ50 synthase BovM, and lay
      a foundation for the further investigation of catalytic mechanism of class II
      lantibiotic synthase LanM. METHOD: The truncated proteins of BovM containing the
      N-terminal dehydratase domain or C-terminal cyclase domain were expressed in E.
      coli and purified. Substrate BovA, the precursor of bovicin HJ50, was incubated
      with these truncated BovM proteins in in vitro reaction system. The antimicrobial
      activity assay and MALDI-TOF MS analysis were used to monitor the dehydratase or
      cyclase activity of these truncated proteins. Meanwhile, the synergistic
      activities of both truncated proteins were tested in vivo and in vitro. RESULTS:
      The N- and C-terminal domains of BovM possessed dehydration and cyclization
      activity respectively. However, no synergistic activity was detected between
      these two functional domains. CONCLUSION: The individual functional domains of
      BovM could execute their corresponding functions independently, but the
      intactness of BovM was important for its full modification activity.

PMID- 25958683
TI  - [Cloning, expression and characterization of a lipase gene, lipC24, from
      Burkholderia sp. ZYB002].
AB  - OBJECTIVE: We cloned a lipase gene, lipC24, from Burkholderia sp. ZYB002 and
      characterized the recombinant lipase LipC24. METHOD: Based on the known genomic
      DNA sequence from Burkholderia cecapia JK321, we designed a pair of specific
      primers for the lipC24 gene and then obtained the full length of lipC24 gene. The
      lipC24 gene fragment enconding the mature peptide LipC24 was then subcloned into
      expression plasmid, pACYC-Duet-lipB, and expressed in E. coli. The recombinant
      protein, LipC24, was purified to homogeneity by HisTrap HP chromatography column
      and HiTrap DEAE FF chromatography column. RESULTS: We expressed the lipC24 gene
      from Burkholderia sp. ZYB002 in E. coli Origami 2(DE3). Nucleotide sequencing
      revealed that the lipC24 gene had an open reading frame of 1317 bp, and the
      deduced amino acid sequence of LipC24 corresponded to 438 amino acid residues,
      including a conserved -G-X1-S-X2-G- motif. The relative molecular weight of the
      purified LipC24 was about 45 kDa. The purified LipC24 displayed hydrolysis
      activity to various 4-nitrophenyl esters and substrate preference for the medium
      chain length 4-nitrophenyl-esters. The optimal temperature was 40 degrees C and
      the optimal pH was 7.5. The lipase was stable between pH 7.0 and 8.0 for 24
      hours. However, the half-life was only 16 min at 40 degrees C. CONCLUSION: The
      LipC24 was a 45 kDa protein, a mesotherm and neutral lipase.

PMID- 25958684
TI  - [Cloning and expression of protease PT121 from Pseudomonas aeruginosa and
      application in peptide synthesis].
AB  - OBJECTIVE: We studied the cloning and expression of lasB encoding solvent
      resistant protease from Pseudomonas aeruginosa PT121. The recombinant protease
      was then characterized and applied in peptide synthesis. METHODS: The PCR primers
      were designed to acquire the open read frame (ORF) of lasB according to similar
      protease gene (pseudolysin) reported in the literature. Inducible expression
      plasmid pET22b-lasB' was constructed and expressed in E. coli BL21 (DE3). The
      recombinant protease was then characterized and applied in peptide synthesis.
      RESULTS: The protease PT121 was defined as metalloproteinase M4 family according
      to sequence blast. Gene sequence analysis shows that lasB encodes signal peptide,
      pro-peptide and mature peptide. Mature protein contains 301 residues with
      molecular weight of 33 kDa. One-step preparation of the recombinant proteases
      PT121 was optimized by breaking cell wall. The specific activity of protease
      PT121 reached up to 7700U/mg, and it was stable similar with wild type PT121 from
      P. aeruginosa PT121 in temperature, pH and organic solvent. The synthesis rate of
      various dipeptides in 50% DMSO was effective, especially productivity of
      aspartame precursor reached up to 91%. CONCLUSIONS: Successful hetero-expression
      of protease PT121 lays the foundation of studying mechanism of catalysis and
      molecular evolution.

PMID- 25958685
TI  - [Effects of methyl bromide fumigation on community structure of denitrifying
      bacteria with nitrousoxide reductase gene (nosZ) in soil].
AB  - OBJECTIVE: We studied the effect of methyl bromide fumigation on soil edaphic
      denitrification. METHODS: We adopted nosZ-PCR-RFLP (restriction fragment length
      polymorphism) method, nosZ-MPN-PCR (Most-Probable-Number- PCR) counting method
      and soil nitrate elimination rate method, to explore the effect of methyl bromide
      fumigation on community structure, quantity and activity of denitrifying bacteria
      in soil. RESULT: After methyl bromide fumigating soil for 100 d, soil
      denitrification did not change obviously (P > 0. 05). Margalef index, Shannon
      wiener index and Evenness index had no significant difference (P > 0.05) in nosZ
      denitrifying bacterial communities between fumigated soil and the control. There
      were Rhodopsendomonas, Pseudomonas fluorescens, Herbacspirillum, uncultured
      bacterium partial in both of them. However, Azospirillum, Rhizobium melibei,
      Nitrosospira multiformis were exclusively found in the control, and Uncultured
      Azospirillum sp, Mesorhizobium sp were in fumigated one. Moreover, the number of
      denitrifying bacteria in the control resolved by nosZ-MPN-PCR (Most-Probable
      Number-PCR) was 1.4 times higher than that of the fumigated one. CONCLUSION:
      After 100 d fumigating soil, the composition of nosZ denitrifying microbial
      community and the population of denitrifying bacteria changed. Furthermore, there
      was no difference in denitrification between the fumigated soil and the control.

PMID- 25958687
TI  - [Construction and characterization of a gspL mutant of avian pathogenic
      Escherichia coli].
AB  - OBJECTIVE: To study the role of gspL gene in avian pathogenic Escherichia coli.
      METHODS: The gspL mutant of Avian pathogenic Escherichia coli (APEC) was
      constructed by homologous recombination assay. The growth characteristics, the
      ability of adhesion and invasion to DF1 cells, the virulence genes transcription
      level and median lethal dose (LD50) were analyzed between the gspL mutant strain
      and the wild strain. RESULTS: Compared with the wild strain, the mutant strain
      had no significant difference in the growth status. However, its ability of
      adhesion and invasion was significantly lower. The transcription of genes pfs,
      fyuA, iss and vat increased obviously, the tsh decreased and the transcription
      level of luxS, ibeA, stx2f and ompA had no significant change. LD50 showed that
      the gspL mutant strain had 12-fold increase in virulence. CONCLUSION: The
      deletion of gspL gene could abate the ability of adhesion and invasion, regulate
      and control some virulence gene transcription level, enhance the virulence of
      APEC. The results show that the gspL gene play roles in pathogenicity of APEC.

PMID- 25958686
TI  - [Screening, identification and characterization of a quinclorac-degrading
      Arthrobacter sp. MC-10].
AB  - OBJECTIVE: We screened and isolated bacterial strains from the perennial
      administration quinclorac paddy fields to degrade quinclorac. METHODS: Strain MC
      10, which can degrade quinclorac efficiently, was screened by enrichment and
      selective medium. The strain was identified by morphological, physio-biochemical
      characteristics and 16S rDNA gene sequence analysis. RESULTS: MC-10 was
      identified as Arthrobacter sp. Under the optimal growth conditions with inoculum
      concentration of 5%, at 28  degrees C, pH 7 for 7 d, MC-10 degraded more than 90%
      of quinclorac. MC-10 can effectively degrade quinclorac when quinclorac initial
      concentration at 1 mg/L--100 mg/L. And the strain MC-10 has a good ability to
      survive in the soil. More than 70% quinclorac in the soil can be degraded
      efficiently after 7 days of cultivation. CONCLUSION: Arthrobacter sp. MC-10 could
      be a promising microorganism in dealing with quinclorac pollution.

PMID- 25958688
TI  - [Identification and pathological observation of a pathogenic Plesiomonas
      shigelloides strain isolated from cultured tilapia (Oreochromis niloticus)].
AB  - OBJECTIVE: A mass mortality of tilapia broke out in an aquaculture farm in Panyu,
      Guangdong Province in May, 2013. Affected fish showed blackening of body color,
      haemorrhageing on surface, scales shedding, fin rotting, and the presence of
      yellow liver, dark red spleen, enlarged gallbladder and ascitic fluid in the
      abdominal cavity. The purpose of this research was isolating and identifying the
      pathogen. METHODS: We isolated a suspicious bacteria strain PYS1 from diseased
      fish with significant pathological signs. The homology of 16S rRNA gene sequence
      of strain PYS1 and its morphological, cultural, and physical and chemical
      characteristics were studied for its identification. Its pathogenicity was
      investigated by recursive infection experiment and histopathological study. Its
      effective medicines was screened by antibiotic sensitive test. RESULTS: The
      results showed that strain PYS1 was Plesiomonas shigelloides clustered with P.
      shigelloides strains isolated from other fishes in the molecular phylogenetic
      tree of 16S rRNA gene sequences. Strain PYS1 was multiple drug resistant and only
      sensitive to a small part of 31 tested antibiotics (e.g., ceftriaxone, cefaclor,
      cefazolin, etc.). The symptoms of tilapia (O. niloticus) artificially infected
      with strain PYS1 were similar with natural infected fish. The half lethal dose
      (LD50) of strain PYS1 to tilapia was 1.425 x 10(8) CFU per fish. Paraffin
      sections showed intestine, liver, spleen, kidney and heart tissue injury caused
      by the strain. CONCLUSION: Our study demonstrated that P. shigelloides was the
      pathogen of cultured tilapia in the aquaculture farm and first reported its
      bacterial pathogenicity on Nile tilapia.

PMID- 25958689
TI  - [Construction of genetically engineered strain producing 5- oxomilbemycin by
      knocking out milF in Steptomyces hygroscopicus HS023].
AB  - OBJECTIVE: To construct a 5-oxomilbemycin producing strain by knocking out milF
      gene in Streptomyces hygroscopicus HS023. METHODS: Plasmid pMSST-DeltamilF was
      constructed and introduced into milbemycin industrial strain Streptomyces
      hygroscopicus HS023, and milF mutant F2-18 was selected by PCR amplification.
      RESULTS: Fermentation experiments showed that no milbemycins was produced in F2
      18, but 5-ketomilbemycin, the intermediate of milbemycin, was obviously
      accumulated, and the fermentation titer was enhanced. CONCLUSION: Genetically
      engineered strain can simplify the synthesis of milbemycin oxime and lepimectin
      chemical from milbemycin.

PMID- 25958690
TI  - [Funding for Division of Microbiology in 2014 by National Natural Science
      Foundation of China].
AB  - In this paper, we provided an overview of proposals submitted and projects funded
      in 2014 at the Division of Microbiology, Department of Life Sciences, National
      Natural Science Foundation of China. The traits and problems in different sub
      disciplines were analyzed, the background, results and analysis of internet
      voting before panel meetings in Microbiology discipline were also introduced. The
      information will provide references for Chinese researchers to apply funding in
      microbiology discipline in the future.

PMID- 25958691
TI  - [Cyclic diadenosine monophosphate--a new second messenger in bacteria--a review].
AB  - Cyclic diadenosine monophosphate (c-di-AMP), a new second messenger found
      recently in bacteria, regulates various aspects of bacterial physiology,
      including cell growth, cell wall homeostasis and virulence. In addition to its
      functions in bacterial physiology, c-di-AMP represents a putative bacterial
      secondary signaling molecule sensed by eukaryotic host cells and triggers innate
      immunity. The level of c-di-AMP in bacteria is regulated by the activities of
      diadenylate cyclase (DAC) and phosphodiesterases (PDE) , the former harbors a
      DisA_N domain, and the latter a DHH or DHH/DHHA1 domain. This review gives an
      overview on metabolic pathway, regulatory mechanism, receptor proteins and
      biological function of c-di-AMP in bacteria, as well as its application and
      trends of development.

PMID- 25958692
TI  - [Influences of maternal and external environment on the early establishment of
      gastrointestinal microflora of neonatal baby--a review].
AB  - The human intestinal microbiota is essential in nutrients utilization, organ
      development, host metabolism, pathogen resistance, and regulation of immune
      responses. The establishment of early gut microflora in newborn infants
      experiences periods from less to more, simple to complex and unstable to stable
      and can be influenced by various factors. This article summarizes the effects of
      delivery mode, delivery period, rearing methods as well as antibiotics on the
      development of intestinal bacterial community.

PMID- 25958693
TI  - [Isolation, identification of a kappa-carrageenase-producing bacterium and kappa
      Carrageenase characterization].
AB  - OBJECTIVE: The aim of this study was to screen and identify carrageenase
      producing strain from mangrove soil leaf and to characterize produced
      carrageenase. METHODS: The culture medium with kappa-carrageenan as sole carbon
      source was used to isolate the strain exhibiting carrageenase activity. The
      isolated strain was identified by morphology observation and 16S rDNA sequencing.
      kappa-carrageenase produced by Pseudoalteromonas sp. ASY5 was purified and
      characterized by DNS method. RESULTS: A bacterial strain ASY5 with high
      carrageenase activity was isolated from mangrove soil humus, and was identified
      as Pseudoalteromonas sp. The molecular mass of the purifiedenzyme was estimated
      to be 30 kDa. The optimal temperature and pH of the enzyme were 60 degrees C and
      7.5, respectively. The enzyme was stabileat 50 degrees C, and more stable between
      pH 7.0 and 9.0. The enzyme could convert kappa-carrageenan. The Km and Vmax
      values of the enzyme for kappa-carrageenan was 2.28 mg /mL and 147.06 MUmol/(min
      . mg), respectively. The enzyme was significantly stimulated by Na+, K+, Ca2+,
      Mg2+ and Al3+. The enzyme was inhibited strongly by Ag+, Zn2+, Cd2+ and SDS.
      CONCLUSION: kappa-carrageenase produced by Pseudoalteromonas sp. ASY5 was stable
      at high temperature and alkaline pH, with potential application in carrageenan
      oligosaccharides production.

PMID- 25958694
TI  - [Homologous cloning and expression of PDS gene from Dunaliella salina in
      Escherichia coli].
AB  - OBJECTIVE: Phytoene desaturase PDS is a eukaryotic nuclear membrane binding
      protein, we used different expression methods to search for the soluble
      expression strategy of membrane binding protein in Escherichia coli. METHODS: We
      cloned the full-length cDNA sequence of PDS from Dunaliella salina through RACE.
      First, we utilized prokaryotic expression vector pET-28a to construct pET-28a-PDS
      vector. Then, we substituted PLtac promoter for T7 promoter in pET-28a to
      construct pET-PLtac-PDS vector. Last, we constructed pET-Mistic-PDS fusion vector
      by integrating Mistic sequence into pET-28a. All were transformed into BL21(DE3)
      for protein expression. RESULTS: The 2237-bp full-length cDNA sequence of PDS was
      cloned, including a 1749-bp open reading frame, encoding 582 amino acids (NCBI
      accession: GQ923693.1). The expression of PDS protein was low via pET-28a-PDS and
      pET-PLtac-PDS vector, and proteins were mostly expressed in inclusion body. The
      expression of PDS protein was significantly increased via pET-Mistic-PDS vector,
      in addition most were expressed as soluble protein which possessed dehydrogenase
      activity. CONCLUSION: Mistic as the solubilization label was able to promote
      proper folding of membrane proteins and improve solubility. Protease activity
      assay proved that Mistic could maintain the enzyme activity.

PMID- 25958695
TI  - [Identification of rpoE gene associated with biofilm formation of Salmonella
      pullorum].
AB  - OBJECTIVE: In order to identify Sigma factor associated with biofilm formation of
      Salmonella pullorum, we determined the gene expression in the wild type strain
      and biological characteristics of deletion mutants. METHODS: Biofilm forming
      ability of S. pullorum strain was detected by crystal violet assay. The rpoS gene
      dependent or -independent strain for biofilm formation was determined by catalase
      test. Real-time PCR was established to compare the expression of six different
      Sigma factors during biofilm formation. Deletion mutants were constructed using
      the Red recombination system, and their resistance to environmental stress was
      determined. RESULTS: S. pullorum strain S6702 had strong ability of biofilm
      formation. The result of catalase test was negative, indicating that S6702 was an
      rpoS-independent strain for biofilm formation. The expression of rpoE gene was
      the highest during 4 h and 24 h post-incubation. Compared to wild-type strains,
      DeltarpoS kept the biofilm-forming ability, whereas DeltarpoE mutant could not
      produce biofilm. Both mutants with deletion of the rpoS and rpoE genes had
      reduced resistance to environmental stress. CONCLUSION: The rpoE gene was
      identified as one of biofilm formation associated genes in a S. pullorum rpoS
      independent strain. The finding may help to elucidate the regulatory mechanism of
      Salmonella biofilm formation.

PMID- 25958696
TI  - [Limiting metabolic steps in the utilization of D-xylose by recombinant Ralstonia
      eutropha W50-EAB].
AB  - OBJECTIVE: To further improve the efficiency of xylose fermentation by modifying
      the pentose phosphate pathway (PPP) and the aldehyde reductase gene h16_A3186 in
      Ralstonia eutropha W50-EAB. METHODS: The transketolase (tktA, cbbT2) and
      transaldolase (tal) gene were cloned from R. eutropha chromosome by PCR and
      inserted into expressing vector pBBR1MCS-3. The resulting recombinant plasmids
      were transformed into W50-EAB to generate W50-KAB, W50-CAB and W50-TAB,
      respectively. The aldehyde reductase gene h16_A3186 was shortened from 834 bp to
      135 bp by in-frame deletion from strain W50-E in which the xylE gene coding for
      xylose transporter was chromosomally integrated to construct recombinant strain
      W50'-E. Then the xylAB gene coding for xylose isomerase and xylulokinase from
      Escherichia coli were expressed in W50'-E to generate recombinant strain W50'
      EAB. Recombinant plasmid pWL1-TAL was transformed into W50'-EAB to construct the
      strain W50'-TAB. The fermentation characteristics of the engineered strains were
      investigated. RESULTS: The expression of tktA, cbbT2 and tal genes in R. eutropha
      W50-EAB was confirmed by enzyme assay. The deletion of h16_A3186 gene was
      confirmed by PCR analysis and enzyme assay. Amplification of transketolase
      activity in R. eutropha W50-EAB showed negative effect on cell growth and D
      xylose consumption. The recombinant strain W50-TAB and W50'-EAB exhibited a
      faster growth than W50-EAB with the maximum specific growth rate of 0.039 h(-1)
      and 0.040 h(-1), respectively, when cultivated on 0.1 mol/L D-xylose. And the PHB
      accumulation of W50-TAB and W50'-EAB reached 16.2 +/- 1.01% and 19.8 +/- 1.05% on
      the basis of cell dry weight, respectively. Furthermore, recombinant strain W50'
      TAB exhibited better fermentation performance with the maximum specific growth
      rate of 0.042 h(-1) and PHB content of 27.9 +/- 0.47%, respectively. Meanwhile,
      the recombinant strains W50-TAB, W50'-EAB and W50'-TAB showed higher biomass and
      more PHB accumulation when using glucose (0.01 mol/L) and D-xylose (0.09 mol/L)
      mixed sugars as fermentative substrate. CONCLUSION: Overexpression of the tal
      gene resulted in incressed D-xylose consumption. Deficiency of the aldehyde
      reductase relieved inhibition to D-xylose metabolism. Combination of the two
      strategies contributed to a higher efficiency of D-xylose utilisation and more
      PHB accumulation of the engineered R. eutropha strain.

PMID- 25958697
TI  - Contamination of Phenylobacterium in several human and murine cell cultures.
AB  - OBJECTIVE: To identify and characterize an unknown microorganism causing
      contamination in several mammalian cell cultures. METHODS: This bacterium was
      identified by 16S rRNA sequencing and studied by DAPI and DiOC6 (3) staining,
      Gram staining, acid-fast staining, and electron microscopy. The isolated
      bacterium was also used to infect host cells to observe antibiotic effectiveness
      and its relationship with host cells. RESULTS: The 16S rRNA sequence analysis
      shows that this rod-shaped microorganism belongs to the family Caulobacteraceae,
      class Alphaproteobacteria, and was most closely related to Phenylobacterium
      zucineum HLK1T strain. The bacterium collected in the "swimming" stage was Gram
      staining negative, but Gram staining positive in the "sessile" stage. Under the
      electron microscope both flagellated and non-flagellated types were found. So
      far, no antibiotics were effective to inhibit this microorganism. The
      contamination with this bacterium frequently led to failed resuscitation of
      thawed cells. We found that the cells resuscitated with the used culture
      supernatants were increased in number by 3-4 folds as compared to those
      resuscitated with freshly prepared media. CONCLUSION: Phenylobacterium may have a
      dimorphic life cycle including a swimming stage and a sessile stalked stage.

PMID- 25958698
TI  - [Function of Mms6 related to biomineralization in Magnetospirillum magneticum AMB
      1 with magnetosomes formation].
AB  - OBJECTIVE: The function of Mms6 related to biomineralization on the magnetosome
      formation in Magnetospirillum magneticum AMB-1 was studied. METHODS: The
      transcript of mms6 was analyzed under static and aerobic conditions with Real
      time RT-PCR. We observed the cell growth and magnetism of the mutation in which
      mms6 was mutated. RESULTS: The transcript of mms6 increased with the formation of
      magnetosomes. Mutation of mms6 caused about 50% decrease of magnetism in AMB-1
      under static conditions, however, the cell growth of mutant was similar as to
      that of the wild type. CONCLUSION: Gene mms6 is involved in the magnetosome
      formation of AMB-1.

PMID- 25958699
TI  - [Comparison of the binding activity of Lactococcus lactis peptidoglycan protein
      anchor with different number of motifs].
AB  - OBJECTIVE: The aim of the present study was to compare the binding activity of
      Lactococcus lactis peptidoglycan protein anchor (PA) with different number of
      motifs. METHODS: L. lactis PA gene sequences with 2 and 3 lysin motifs (LysM)
      were obtained by PCR amplification. Then, the recombinant plasmid of pET-32a(+)
      containing PA gene was constructed and transformed into E. coli BL21 (DE3) , and
      induced to express the fusion protein PA2 and PA3. The purified and refolded PA2
      and PA3 were incubated with gram positive enhancer matrix (GEM). The binding
      activities of PA2 and PA3 were identified and compared by Western blot, TEM and
      SDS-PAGE. RESULTS: The PA2 and PA3 could bind to GEM. The anchoring activity of
      PA3 was obviously superior to the PA2. CONCLUSION: The data indicated that PA
      with 3 LysMs had a better binding capacity compared with 2 LysMs. The results
      provided foundations to further improve the design of GEM-PA display system.

PMID- 25958701
TI  - [Microbial distribution and 16S rRNA diversity in the rhizosphere soil of Panax
      notoginseng].
AB  - OBJECTIVE: We studied the correlation between the microbial diversity in Panax
      notoginseng root soil and its root rot diseases, to find biological control
      approaches in Panax notoginseng soil borne diseases. METHODS: We isolated
      bacterial strains from the rhizosphere soils of healthy and root rot Panax
      notoginseng plants that are cultured continuously for 6 years in Wenshan Region.
      After separation and purification, we obtained DNA. On the basis of 16S rRNA' s
      general primer we carried out PCR amplification, conducted blast gene similarity
      and analyzed phylogenetic information. RESULTS: The isolated bacterial strains
      distributed to 4 phyla, 40 genera of bacteria, 179 isolates from the samples of
      healthy Panax notoginseng rhizosphere soil belong to 30 genera and Burkholderia,
      Arthrobacter, Streptomyces and Bacillus are the dominant microflora.
      Additionally, 117 isolates from the samples of root rot Panax notoginseng
      rhizosphere soil belong to 29 genera and Ralstonia, Sphingomonas,
      Stenotrophomonas as the dominant microflora. Among them, Flavobacterium and
      Enterobacter were only isolated from the samples of root rot Panax notoginseng
      rhizosphere soil. At least 5 isolates are novel species; the ions concentration
      and electrical conductivity value show distinct discrepancy between the two
      groups (P < 0.05); the microbial amount of dominant species in the healthy soil
      samples present negative correlation with electrical conductivity value, the
      concentration of NO3-, SO4(2-), CO3(2-), K+ and total salt (P < 0.01).
      CONCLUSION: In addition to pathogen infection, the physical and chemical
      characteristics, microbial community structure and the proportion of dominant
      species are also closely related to notoginseng continuous cropping soil borne
      disease. Especially the beneficial microorganisms (Burkholderia, Bacillus,
      Streptomyces, etc.) abundance is significant to evaluate the soil healthy
      condition and accurately disease control & forecast for Panax notoginseng
      cultivation.

PMID- 25958700
TI  - [Effect of non-classical secreted proteins on LipaseA secretion].
AB  - OBJECTIVE: We used 50-amino acid-long peptides from the N-terminus of 4 different
      non-classically secreted proteins to study the secretion efficiency of Bacillus
      subtilis LipaseA via non-classical secretion pathway. METHODS: We amplified the
      coding sequences (CDs) of LipaseA and N-terminus of non-classically secreted
      proteins, constructed 8 fusion protein expression vectors containing both LipaseA
      CD and different secretion signal peptide and transformed them into B. subtilis
      WB800. Secretion efficiency of these fusion proteins was analyzed by enzyme
      activity, SDS-PAGE and Western-Blot. RESULTS: Recombinant LipaseA containing
      coding sequences of PdhA or N-terminus of SodA and Eno as secretion signals was
      efficiently secreted. CONCLUSION: Parts of non-classically secreted proteins or N
      terminus (50 amino acids) could guide LipaseA protein secretion.

PMID- 25958702
TI  - [Mycorrhizal fungi diversity of Vaccinium uliginosum L].
AB  - OBJECTIVE: The diversity of mycorrhizal fungi isolated from Vaccinium uliginosum
      L in the northern region of Daxing' anling mountains was examined for the first
      time. METHODS: Morphology and ITS sequence analysis were used to identify the
      fungal communities. RESULTS: Six groups of fungi were isolated from Vaccinium
      uliginosum root samples: one belongs to Hymenoscyphus; one to Phialocephala; one
      to Lachnum; one to Cadophora; one to Marasmius and one to Mycena. Among them, 87.
      10% belong to ascomycetes and 12.90% belong to Basidiomycotina. CONCLUSION: The
      diversity of fungi associated with Vaccinium uliginosum is abundant and the fungi
      are from heterogenous group.

PMID- 25958703
TI  - [Immunogenicity evaluation of Mycobacterium tuberculosis MPT83 protein and
      establishment of serological diagnostic method for bovine tuberculosis
      detection].
AB  - OBJECTIVE: The aim of this study was to express Mycobacterium tuberculosis MPT83
      protein and to evaluate its immunogenicity in murine model as well as the
      serological diagnosis potential value for bovine tuberculosis. METHODS: The
      fragment of mpt83 gene was amplified and constructed into pET30a(+)-mpt83
      recombinant plasmid. MPT83 fusion protein was purified with His affinity
      chromatography column from strain of BL21(DE3)-pET30a(+)-mpt83 after induced by
      IPTG, and then used to evaluate its immunogenicity in mice and the potential
      application in ELISA assay for the detection of bovine tuberculosis. RESULTS: SDS
      PAGE and Western blot results show that MPT83 fusion protein was expressed
      successfully and possessed a good immunological reactivity. Flow cytometry (FCM)
      analysis displayed decreased expression of CD80 on dendritic cells and up
      regulation of CD69 expression on both splenic CD4+ and CD8+ T cells. Meanwhile,
      more IL-4 specific secreting cell spots rather than those of IFN-gamma were
      detected by ELISPOT assay in C57BL/6 mice injected with the fusion protein. Total
      200 serum samples were detected by indirect ELISA based on MPT83 as antigen and
      the results showed 48.6% positive coincidence rate and 90% negative's compared to
      results of peripheral blood specific IFN-gamma release assay in bovine
      tuberculosis detection. CONCLUSIONS: MPT83 fusion protein was expressed
      successfully with capability of eliciting Th2 immune response in mice and could
      be used for ELISA assay to detect bovine tuberculosis as a serological diagnosis
      antigen.

PMID- 25958704
TI  - [Serological tests of the truncated TTSuV2 ORF1 recombinant proteins with the
      porcine sera].
AB  - OBJECTIVE: We studied the serological response between the special regions on the
      Torque teno sus virus 2 (TTSuV2) ORF1 coded protein and the porcine sera from
      conventional pigs. METHODS: Based on a Chinese TTSuV2 strain from Guangdong
      province, two overlapped virus proteins were expressed from Escherichia coli.
      Then, purified recombinant TTSuV2 ORF1a and TTSuV2 ORF1ab proteins were used as
      the antigens in the Western Blotting and ELISA assay. RESULTS: The recombinant
      TTSuV2 ORF1a and TTSuV2 ORF1ab proteins were identified with the special tag
      monoclonal antibody. The results of the ELISA tests shown that there were
      significant relationships between two groups of dates from the recombinant TTSuV2
      ORF1a and TTSuV2 ORF1ab proteins antigenic assay. The results of the following
      Western Blotting assay indicated that the TTSuV2-specific IgG antibodies were
      contained in pig sera. CONCLUSION: The truncated TTSuV2 ORF1a protein (positions
      168 to 346 corresponding to TTSuV2 GDIMA1) contains important B cell epitopes
      which can stimulate immune system antibody secretion. The truncated TTSuV2 ORF1a
      protein could be effective in TTSuV2 immunodiagnosis.

PMID- 25958705
TI  - [Antitumor mechanism of Bursopentin (BP5)].
AB  - OBJECTIVE: Bursopentin (BP5) is a multi-functional bioactive peptide with
      functions of immunomodulatory, antioxidant and antitumor. However, the antitumor
      mechanism of BP5 is still unclear. METHODS: We constructed T7 phage cDNA library
      of DT40 cells, and the proteins interacted with BP5 were identified. Then, the
      expression profile of BP5-treated DT40 cells were analyzed using gene microarray,
      p53 Luciferase activity was detected. RESULTS: The results of the expression
      profiling revealed that BP5 regulated expression of 1078 genes, of which 537 were
      up-regulated and 541 were down-regulated. Differentially expressed genes involved
      in various pathways were identified, of which 25 pathways were associated with
      immune responses and tumorigenic processes, including the p53 signaling.
      Furththmore, BP5 significantly enhanced p53 luciferase activity and stimulated
      expression of p53 protein in HCT116 cells. CONCLUSION: These results suggest that
      BP5 exerted antitumor activity through p53 signaling and that this study provides
      novel insights on the antitumor mechanism of BP5.

PMID- 25958706
TI  - The factors associated with mild cognitive impairment (MCI) in surgical menopause
      women.
AB  - BACKGROUND AND OBJECTIVE: As a sizeable proportion of persons with mild cognitive
      impairment will progress to frank dementia, early detection is an important
      strategy to prevent and decelerate the progression of cognitive decline. In
      Thailand, the prevalence of mild cognitive impairment in surgical menopause women
      has not been well established. The objectives of the present study were to
      determine the percentage and factors associated with mild cognitive impairment in
      women with surgical menopause. MATERIAL AND METHOD: Between October 2013 and July
      2014, 200 eligible women at King Chulalongkorn Memorial Hospital were enrolled.
      The self-reported questionnaires were used to obtain the demographic data and the
      Thai version of the Montreal Cognitive Assessment (MoCA) was used to detect mild
      cognitive impairment (MCI). The MCI was diagnosed when the MoCA score was less
      than 25. The data were statistically analyzed using SPSS version 17 for student t
      test, Chi-square test, and multiple regression analysis. RESULTS: The percentage
      of MCI in the present study was 43.5%. The univariate analysis showed that
      factors significantly related to MCI were marital status, educational levels,
      occupation, monthly income, and duration of hormone replacement therapy (HRT).
      Nevertheless, multiple regression analysis revealed that only older age at
      enrollment, marital status, low educational level, and low monthly income were
      significantly related to MCI. CONCLUSION: Almost half of the surgical menopause
      women in the present study had MCI. Older age at enrollment, marital status, low
      educational level, and low monthly income were significantly related to MCI. Age
      at surgical menopause and HRT were not found to be associated with MCI in this
      study.

PMID- 25958708
TI  - High-frequency oscillatory ventilation for patients during exudative phase of
      severe ARDS.
AB  - BACKGROUND: High frequency oscillatory ventilation (HFOV) is theoretically ideal
      for lung protective strategy ventilation (LPSV) in acute respiratory distress
      syndrome (ARDS). However, recent studies revealed unsatisfactory outcomes. The
      authors conducted a study to examine this phenomenon in patients with early phase
      of moderate to severe ARDS. OBJECTIVE: To evaluate the effectiveness of HFOV in
      patients with early phase of moderate to severe ARDS. The primary outcome was 30
      days all-cause mortality. MATERIAL AND METHOD: The study was a matched-case
      controlled clinical trial performed in the medical intensive care units, Faculty
      of Medicine, Siriraj Hospital. The authors compared HFOV with LPSV in adult
      patients with the early phase of ARDS who received mechanical ventilation less
      than 72 hours and had moderate to severe hypoxemia (PaO/FiO2 ratio less than or
      equal 150). RESULTS: Between June 2010 and February 2014, 49 patients with
      moderate to severe ARDS were included. Fourteen patients who received HFOV were
      matched with 16 patients who received LPSV. The 30-day mortality in HFOV group
      was 61.5%; while in control group, 50% (p = 0.53). The authors found use of
      higher doses of sedative drugs and muscle relaxants in HFOV group. In addition,
      this group had high-level of mean airway pressure (mPaw). The presence of
      hemodynamic instability was not different in both groups. CONCLUSION: In adult
      patients in the early phase of moderate to severe ARDS who received mechanical
      ventilation for less than 72 hours, HFOV did not decrease the 30-day mortality.
      Thus, this support should be only a rescue therapy for refractory hypoxemia cases
      and in highly selected patients.

PMID- 25958707
TI  - Comparison between disease free survival of hepatocellular carcinoma after
      hepatic resection in chronic hepatitis B patients with or without cirrhosis.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients
      can develop in those with cirrhotic and non-cirrhotic liver Not only impairment
      of liver status, but also the extension of tumor and difference of pathogenesis
      may also affect characteristics of patient and tumor including survival and
      recurrence. OBJECTIVE: To evaluate the disease free survival, prognostic factors
      and features of HCC after hepatic resection in CHB patients with and without
      cirrhosis. MATERIAL AND METHOD: Two hundred fifteen HBV-related HCC patients
      underwent hepatic resection and were analyzed. Cirrhotic and non-cirrhotic groups
      were compared for differences inpatient and tumor characteristics, disease-free
      survival including prognostic factors. RESULTS: In comparison with cirrhotic
      patients, non-cirrhotic patients had more family history of HCC, more preserved
      liver function, were less HBeAg positive, and had lower HBV viral load. HCC
      characteristics in non-cirrhotic groups showed significantly larger (5.8 +/- 3.7
      vs. 4.9 +/- 3.9 cm, p = 0.036) and operative data revealed that non-cirrhotic
      patients underwent more major surgery (50.7 vs. 18.3%, p < 0.001), and had
      shorter hospital stay (10.8 +/- 8.9 vs. 8.1 +/- 4.3 days, p = 0.006) than
      cirrhotic ones. Operative time, blood loss and requirement of PRC transfusion
      were similar in both groups. Pathological profiles of HCC and liver parenchyma
      were comparable in both cirrhotic and non-cirrhotic patients. The disease-free
      survival of non-cirrhotic patients was longer than cirrhotic patients (Median
      disease free survival were 21 and 11 months respectively, p = 0.022). The
      independent predictive factor of lower disease-free survival of non-cirrhotic CHB
      patients who underwent hepatic resection was lymph node involvement (Hazard ratio
      (HR), 4.598. 95% confidence interval (CI), 1.1-19.212; p = 0.037) while of
      cirrhotic patients, factors were age > 50 years old (HR, 2.998; 95% CI, 1.298
      6.925; p = 0.01), multifocal tumor (HR, 5.835; 95% CI, 1.122-30.342; p = 0.036)
      andportal vein involvement (HR, 3.722; 95% CI, 1.121-12.353; p = 0.032). HBV
      treatment after HCC diagnosis was a significant predictor in the cirrhotic group
      by univariate analysis (p = 0.04). CONCLUSION: Imaging and histological findings
      of HCC in cirrhotic and non-cirrhotic CHB patients were not different, except for
      larger tumor size in non-cirrhotic patients. Lymph node involvement is the
      predictor of HCC recurrence in non- cirrhotic CHB patients. Age > 50 year old and
      multifocal tumor and portal vein involvement are the predictors of HCC recurrence
      in cirrhotic CHB patients. These groups may need surveillance that is more
      intensive after hepatic resection. Antiviral therapy may lower the risk of HCC
      recurrence among CHB cirrhotic patients.

PMID- 25958709
TI  - C-reactive protein as a single useful parameter for discontinuation of antibiotic
      treatment in Thai neonates with clinical sepsis.
AB  - BACKGROUND: Clinical sepsis is a common diagnosis in neonate and is usually
      treated with antibiotic. The duration of treatment is usually more than five days
      or until all cultures from the patient's samples reveal negative. OBJECTIVE: To
      determine whether quantitative C-reactive protein (CRP) level less than 10 mg/L
      could be used as a reliable index for discontinuation of antibiotic treatment in
      Thai neonates with clinical sepsis. MATERIAL AND METHOD: All neonates with birth
      weight greater than 1,500 grams, diagnosed as clinical sepsis, were enrolled to
      the study. Serum CRP was measured at 24 to 48 hours after the first dose of
      antibiotics. If CRP level was less than 10 mg/L, infants were randomly divided to
      groups Ia and Ib. If CRP level was 10 mg/L or more, infants were randomly divided
      to groups IIa and IIb. Antibiotics were discontinued promptly after the CRP level
      was reported in group Ia, while CRP level was measured daily and antibiotics were
      discontinued after it returned to less than 10 mg/L in group IIa. In controlled
      groups (Ib and IIb), antibiotics were continued until all bacterial cultures were
      negative. The outcome measurements were the number ofpatients who required
      retreatment for clinical sepsis within three days and 28 days after discontinuing
      antibiotics. RESULTS: Of 98 neonates with clinical sepsis, 76 (77.6%) were in
      group I. The duration of antibiotic treatment in group Ia was shorter than group
      Ib significantly, 1.68 vs. 5.47 days (p < 0.01). One neonate in group Ia was
      retreated on the third day after discontinuing antibiotics due to positive blood
      and urine cultures. The negative predictive value of CRP for discontinuation of
      antibiotics in group I was 97.4%. The durations of antibiotic treatments were
      5.27 and 7.09 days in group IIa and IIb, respectively. One neonate in group IIa
      was retreated on the second day after discontinuing antibiotics since the
      patient's clinical and laboratory results suggested severe sepsis although all
      bacterial cultures were negative. No patient was readmitted for treatment of
      sepsis within 28 days after discontinuing antibiotics. CONCLUSION: CRP levels
      were less than 10 mg/L in the majority of neonates with clinical sepsis. The
      negative predictive value for using this level as a guide for antibiotic
      discontinuation was 97.4%.

PMID- 25958711
TI  - Vitamin D deficiency and adrenal function in critically ill children.
AB  - BACKGROUND: Data on interrelationship between vitamin D deficiency (VDD) and
      adrenal insufficiency in critically ill children are limited. OBJECTIVE: To
      determine vitamin D status in critically ill children and its relationship with
      adrenal function. MATERIAL AND METHOD: Thirty-two patients and 36 controls were
      included. Serum 25-hydroxyvitamin D (25-OHD) levels were measured. Pediatric Risk
      of Mortality (PRISM) III score, outcome and adrenal function assessed by 1
      microgram adrenocorticotropic hormone test were collected. RESULTS: Median (IQR)
      serum 25-OHD of thepatients was less than that of the controls (16.6 (13.3-19.5)
      vs. 24.2 (21.0-27.9) ng/mnL, p < 0.001). Twenty-five (78%) patients and seven
      (19%) controls had VDD. PRISM III score, proportions of patients with shock and
      vasopressive drug used, length of intensive care unit stay and ventilator used,
      and adrenal function were not different between patients with and without VDD.
      Patients with serum 25-OHD of less than 12 ng/mL had higher median (IQR) PRISM
      III score (14 (6-20) vs. 5 (2-10), p = 0.033) and higher proportion of mortality
      than those with serum 25-OHD of 12 ng/mL or greater. CONCLUSION: A greater
      proportion of VDD in critically ill children as compared with that of the
      controls was demonstrated. Serum 25-OHD was not associated with adrenal function.

PMID- 25958710
TI  - The clinical effect of fentanyl in comparison with ketamine in analgesic effect
      for oncology procedures in children: a randomized, double-blinded, crossover
      trial.
AB  - BACKGROUND: Children often require relief of pain and anxiety when undergoing
      painful procedures. OBJECTIVE: To determine the differences by comparing fentanyl
      and ketamine used in cancer-diagnosed children undergoing painful procedures.
      MATERIAL AND METHOD: A randomized, double-blinded, crossover trial was conducted
      with 55 children undergoing painful procedures (intrathecal chemotherapy and/or
      bone marrow aspiration/biopsy). Patients were randomly assigned in a double
      blinded fashion to receive either intravenous fentanyl or ketamine at 1
      mcg/kg/dose and 1 mg/kg/dose, respectively. The result in effectiveness of the
      drug was measured using three parameters, 1) satisfaction score ranging from 0 to
      10, 2) perception of procedural pain using FLACC scale, Wong-Baker FACES Pain
      Rating Scale and Visual Analog Scale, and 3) the frequency of vomiting nausea
      score. RESULTS: The satisfaction amongpatients receiving fentanyl was
      significantly greater than ketamine (p = 0.007). In addition, both painful and
      nausea/vomiting were significantly decreased in the patients receiving fentanyl
      (p = 0.002 and p < 0.001, respectively). No serious complications were observed
      CONCLUSION: This study demonstrated that intravenous fentanyl generated a
      superior clinical effect in satisfaction, decreased pain and nausea/vomiting, and
      showed no significant side-effects over ketamine. Fentanyl may also be
      recommended as a reasonable option before undergoing oncology procedures in
      children with cancer.

PMID- 25958712
TI  - Facet joint orientation and tropism in lumbar degenerative disc disease and
      spondylolisthesis.
AB  - BACKGROUND: Although degenerative disc disease (DDD) and degenerative
      spondylolisthesis (DS) are two common causes of back pain in elderly, the
      association between the lumbarfacet joint angle and tropism in these conditions
      are still unclear. OBJECTIVE: To evaluate the difference in facet joint angles
      between normal population and lumbar degenerative disc disease and
      spondylolisthesis patient. MATERIAL AND METHOD: The angle of lumbar facet joints
      were retrospectively measured with magnetic resonance imaging (MRI) to determine
      whether there was a difference between degenerative diseases. MRI of patients
      with DDD, DS, and control group at facet joint between L3-4, L4-5 and L5-S1 level
      were measured in axial view (60 subjects in each group). RESULTS: There was no
      difference infacetjoint angle in DDD (44.1 +/- 11.9) and control (45.6 +/- 8.9),
      but differed in DS (40.1 +/- 10. 7) and control group (p = 0.010) at L4-5 level.
      Facet tropism showed difference between degenerative groups and control group at
      L4-5 level. CONCLUSION: DS group showed difference in facet joints angle and
      tropism when compared with control population, while DDD showed difference only
      in facet tropism. In addition, longitudinal studies are needed to understand the
      clinical significant between facet joint angle and tropism in spinal degenerative
      diseases.

PMID- 25958713
TI  - A stress survey in anesthesia personnel in Thailand.
AB  - OBJECTIVE: To find out stressful events related to anesthesia and psychological
      responses in anesthesia personnel. MATERIAL AND METHOD: Three hundred fifty three
      nurses and 286 doctors from all over the country who currently working in
      operating theatres participated in this study. Research tools comprised of
      interactive online anesthesia-related and psychological stress tests. Data were
      analyzed as mean and standard deviations. Comparisons of all associated factors
      between groups were performed by the Kolmogorov-Smirnov Two-Sample test and t
      test independent. Correlations between groups were determined by Spearman's rho
      and Pearson's. Statistical significance was defined as p-value less than 0.05
      with a 95% confidence interval. RESULTS: Nurses expressed greater worries with
      impairment of cognitive and immune functions, particularly on night shifts. They
      had intense responsibility, compounded by lack of experiences and knowledge.
      Doctors were under stress during the day. This depended on their ages,
      experiences, morbidity rumors, working hours, and day off after operation, which
      manifested themselves as disturbances of the autonomic nervous system and
      emotions. CONCLUSION: Nurse anesthetists expressed their worries, particularly on
      night shifts. Their psychological distresses were observed as impairment of
      cognitive and immune functions. Doctors were under professional stress during the
      day, which came across as disturbances of the autonomic nervous systems and
      emotions.

PMID- 25958714
TI  - Cardiovascular effects of volatile induction and maintenance of anesthesia (VIMA)
      and total intravenous anesthesia (TIVA) for laryngeal mask airway (LMA)
      anesthesia: a comparison study.
AB  - OBJECTIVE: To compare changes of heart rate and blood pressure in patients that
      underwent LMA anesthesia with VIMA or TIVA technique. MATERIAL AND METHOD: A
      hundred healthy patients, age 16 to 60 years were enrolled. They were randomized
      into two groups. Patients in group V (VIMA) were induced with 8% sevoflurane
      until loss of eyelash reflexes then controlled ventilation for five minutes
      before LMA insertion. Group T (TIVA) patients were given propofol to reach the
      affected site concentration of eight mcg/mlfor the LMA insertion. Bloodpressure
      and heart rate were recorded before induction, immediately before and after LMA
      insertion then every two minutes until surgical incision. RESULTS: Decreased SBP
      from baseline in group T was significantly more than group V in each period of
      time (D1-D7). DBP in group T decreased more than group V significantly only at
      eight and ten minutes after LMA insertion. The incidence of decreasing SBP > 20%
      from baseline was more significant in group T than group V. No significant
      difference of changed HR was found. Coughing during LMA insertion occurred in
      eight patients (16%) in group T and in three patients (6%) in group V (p = 0.11).
      CONCLUSION: Induction with propofol by effective site concentration of eight
      mcg/ml significantly decreased SBP more than with 8% sevoflurane. Both techniques
      provided smooth LMA insertion without serious complication.

PMID- 25958715
TI  - Ninety days mortality after thoracic endovascular aortic repair.
AB  - BACKGROUND: The thoracic endovascular aortic repair (TEVAR) has become popular
      due to its favorable immediate outcome. However, the outcome in longer duration
      is still questionable. The aim of the present study was to analyze the incidence
      and risk factors associated with 90 days mortality after TEVAR. MATERIAL AND
      METHOD: After the Siriraj Institutional Review Board, Thailand approved and
      waived the needfor the informed consent, the database that included 160
      consecutive patients having TEVAR procedures between December 2006 and December
      2010 was examined Patients' characteristics, including operative procedures and
      anesthesia techniques were studied. The mortality and complications were
      extracted and analyzed. Major adverse events and the others factors were analyzed
      to determine the risk factors. Other complications such as bleeding, endoleak,
      infection, and reintervention were examined and analyzed. RESULTS: One hundred
      sixty patients underwent TEVAR. They included 118 male (74%) and 42 female (26%)
      with mean age of 65. Perioperative mortality (within 24 hours postoperatively)
      was 1 (0.6%), 30 days mortality was 7 (4.4%) and the overall 90 days mortality
      was 10 (6.25%). Causes of death included sepsis [4 patients (2.5%)], multi-organ
      failure [3 patients (1.9%)], ischemic heart disease [1 patient (0.6%)],
      uncontrolled bleeding [1 patient (0.6%)], and graft ruptured [1 patient (0.6%)].
      The risk factor related to mortality was postoperative neurological morbidity (OR
      6.77, 95% CI = 1.08-42.36, p = 0.4). General anesthesia with endotracheal tube
      was used in the majority of the patients (92.5%), with no statistical
      significance in anesthesia-related mortality. Major adverse events including
      pneumonia 11.9%, cardiac arrhythmia 11.3%, graft infection 7.5%, neurological
      complication 7.0% (ischemic stroke 9 andparaplegia 1), renal failure 3.8%, and
      myocardial ischemia 0.6%. CONCLUSION: The incidence of 90 days mortality after
      TEVAR was 6.25% (10 from 160). The risk factor associated with mortality was the
      development of neurologic complication postoperatively.

PMID- 25958716
TI  - Effectiveness of oral zinc supplementation in the treatment of idiopathic sudden
      sensorineural hearing loss (ISSNHL).
AB  - OBJECTIVE: Investigate the benefit of zinc supplement combined with standard
      treatment ofidiopathic sudden sensorineural hearing loss (ISSNHL) patients.
      MATERIAL AND METHOD: A prospective, randomized study was designed to evaluate the
      hearing outcomes in ISSNHL patients treated with zinc supplement. The patients
      were randomized into two groups, the study and the control group. The study group
      received oral chelated zinc with standard treatment (oral prednisolone), while
      the control group received standard treatment alone. Hearing improvement was
      assessed from pure-tone average (PTA) and speech discrimination scores (SDS).
      RESULTS: After treatment, significant hearing improvement was noted in both
      groups regarding PTA value (p = 0.016, 0.025). SDS was also improved in both
      groups but with no statistical significance (p > 0.05). Post-treatment PTA and
      SDS values between the zinc and control groups were not statistically different
      (p > 0.05). Hearing improvement was documented in eight of 16 patients in the
      study group and seven of 14 patients in the control group. This was no
      significant difference (p = 1.000). CONCLUSION: Zinc supplementation does not
      have benefit when combined with standard treatment. Nevertheless, more subjects
      and well-designed studies are needed to verify the effect of zinc.

PMID- 25958718
TI  - Computed tomography evaluation of intracranial vascular calcification in major
      ischemic stroke patients (vascular territory)--its distribution and association
      with vascular risk factors: a retrospective trial.
AB  - OBJECTIVE: Our objective was to determine the distribution of intracranial
      atherosclerotic calcification, its association with risk factors, and
      cerebrovascular events in patients with major ischemic stroke. MATERIAL AND
      METHOD: In this retrospective study, 327 patients who underwent CT scan of brain
      were included and the clinical parameters were recorded. Two neuroradiologists
      evaluated the non-contrast axial CT images for any of intracranial arteries,
      based on a standard CT scoring system for extent (0-4) and thickness (0-4). The
      composite CT score for extent and thickness of these vascular segments or vessels
      were recorded on all patients. RESULTS: Based on of MDCT features, 155 major
      ischemic stroke and 172 non-ischemic stroke were enrolled The highest prevalence
      of calcification was seen in intracranial internal carotid artery (IICA) (73%),
      and less commonly in the vertebral artery (8%). There were higher prevalence of
      intracranial artery calcification in ischemic stroke patients than non-ischemic
      stroke patients (82% vs. 52%, p < 0.0001). Hypertension (OR = 1.903, 95% CI:
      1.019-3.552, p < 0.05), intracranial artery calcification (OR = 2.147, 95% CI:
      1.143-4.033, p < 0.05), moderate degree of calcification (OR = 2.631, 95% CI:
      1.299-5.260, p < 0.05), and severe degree of calcification (OR = 3.479, 95% CI:
      1.500-8.068, p < 0.05) were found to be independently associated with ischemic
      stroke. CONCLUSION: Significant intracranial atherosclerosis as determined by
      severe CT calcification had higher incidence in ischemic stroke patients.
      Intracranial artery calcification with moderate and severe degree of
      calcification and hypertension were independently significant associated with
      ischemic stroke. CT calcification score might serve as an indicator of
      intracranial atherosclerotic disease and might be useful in predicting ischemic
      stroke.

PMID- 25958717
TI  - Comparative outcomes for sclerotherapy of head and neck venous vascular
      malformation between alcohol and bleomycin.
AB  - OBJECTIVE: To assess and compare the effectiveness of the two sclerosing agents
      (95% alcohol and Bleomycin) for the treatment of head and neck venous
      malformation (VM). MATERIAL AND METHOD: The authors retrospectively reviewed our
      experience in treating VM of the head and neck region using two sclerosing
      agents, 95% alcohol (November 2001 to June 2008) and bleomycin (July 2008 to July
      2010). Patients' demography (age, sex), lesion number location, type
      (focal/extensive), and characteristic features (cystic/tubular/mixed) were
      recorded. The treatment outcome was determined by decrease in size of VM in
      photographs taken at one month and at final clinical follow-up. These were
      analyzed by two radiologists using visual rating scale (worst or not improved,
      <50%, 50-75%, >75% of size reduction). One-way Anova test (p < 0.1) was used to
      show the differences in treatment effectiveness of the two sclerosing agents at
      short- and long-term intervals. RESULTS: Thirty-three patients, age ranged from
      11 to 62 years (mean 25.1 years), with 27 female and six male patients were
      included in this study. The majority of patients were less than 16 years (17
      patients, 51%). The 43 lesions were categorized as 28 VMs were focal (65.1%), 15
      (34.9%) diffuse, and30 (69.7%) were of the mixed type. Sixteen lesions were
      treated with 95% alcohol, 23 lesions with bleomycin, and four lesions with a
      combination of the two sclerosants. The range of number of procedures was 1 to 16
      (mean 3.76 procedures per patient) for alcohol, and 1 to 5 (mean 2.27 procedures
      per patient) for bleomycin. The cumulative dose ofsclerosant used was 101 ml for
      alcohol and 32.11 mg for bleomycin. Total follow-up at 1-month and at final was
      43/43.(100%) and 35/43 (81.4%) respectively. Mean follow-up interval was 14.7
      months. Differences in size reduction after treatment by different sclerosing
      agents were found. At more than 1-year follow-up, those treated with bleomycin
      gained graded 3 (> 75%) size reduction more than treated by 95% alcohol. No VM
      treated with 95% alcohol obtained grade 3 of size reduction at 1-year follow-up.
      Multiple regression analysis showed VM's favorable character for bleomycin
      treatment by decreasing mixed, cystic, and tubular Pediatrics had relatively more
      benefit with bleomycin treatment. CONCLUSION: Sclerotherapy using either alcohol
      or bleomycin is an effective treatment for VMs. Different treatment outcomes were
      significant at long-term with group of VM those treated with bleomycin but not at
      short-term (p < 0.1).

PMID- 25958719
TI  - Incidence and risk factors of acute delirium in older patients with hip fracture
      in Siriraj Hospital.
AB  - OBJECTIVE: To determine the incidence and associated factors of delirium in older
      patients admitted with hip fracture. MATERIAL AND METHOD: Eighty patients with
      fall-related hip fracture who admitted to orthopedics wards in Siriraj Hospital
      were recruited. Baseline characteristics, functional ability and cognitive
      status, treatment-related factors, clinical outcomes, length of stay, and direct
      medical cost were evaluated. Delirium was diagnosed by experienced geriatricians
      using DSM-IV RESULTS: Thirty-six patients (45%,) developed delirium. Hyperactive
      and hypoactive delirium was 24:12 patients. Preoperative and postoperative
      delirium was developed in 18:18 patients. Age, TMSE score on admission, modified
      IQCODE score, premorbid mRS, receiving NSAIDs around the clock postoperatively,
      and sedative drug use were significantly different between the non-delirium and
      delirium groups in multivariate logistic regression analysis. Patients with
      delirium did not have significantly higher postoperative complications, hospital
      length ofstay, functional status (mRS) at discharge, mortality, and direct cost
      of the treatment in hospital. CONCLUSION: Delirium is common in elderly hip
      fracture undergoing hip repair. Age, premorbid function, dementia/cognitive
      impairment, NSAIDs, and sedative use were associated factors of delirium.
      Identifying those with high-risk factors should be routinely performed rigorously
      and strategies to reduce delirium incidence and severity should be planned and
      conducted.

PMID- 25958721
TI  - ["Morfologiya" journal in 2014].

PMID- 25958720
TI  - Childhood follicular mucinosis co-existed with alopecia universalis.
AB  - We report a case of a 6-year-old girl presented with diffuse scalp and body hair
      loss and developed multiple groups of follicular papules on the trunk. She was
      diagnosed as follicular mucinosis co-existed with alopecia universalis.
      Histopathological study supported the diagnosis and did not find malignancy
      cells.

PMID- 25958722
TI  - [Distribution of GABAergic neurons in pneumotaxic center nuclei in the early
      postnatal period in norm and in prenatal deficiency of serotoninergic system in
      rats].
AB  - The aim of this study was to determine the distribution of GABAergic neurons in
      pneumotaxic center structures (parabrachial complex medial subnucleus and
      Kolliker-Fuse nucleus) in norm and in deficiency of serotoninergic system during
      the prenatal period of development in Wistar rats. Reduction of endogenous
      serotonin levels in fetal rats was achieved by tryptophan hydroxylase inhibition
      with para-chlorophenylalanine (PCPA), which was administered to female rats on
      Day 16 of gestation. Material was obtained from the area of the pons from
      experimental and control (intact) rat pups at early postnatal (Days 5, 10 and 12)
      and juvenile (Day 20) periods. At each time point, 5-6 animals were studied from
      both experimental and control groups. To demonstrate GABAergic neurons,
      antibodies against glutamate decarboxylase (GAD-67), the enzyme involved in its
      synthesis, were used. The results have shown that Kolliker-Fuse nucleus contained
      a population of GABAergic neurons at early postnatal period, the size of which
      was preserved until juvenile age. In parabrachial complex medial subnucleus
      during the early postnatal period, a small number of GABAergic neurons was
      detected, which was somewhat increased by juvenile age. Serotonin deficiency in
      pneumotaxic center structures lead to a reduction of the numbers of GABAergic
      neurons, GABAergic synapses and their clusters. A reduction of serotonin levels
      during the prenatal period may cause the disturbances in the inhibitory afferent
      signaling of the pneumotaxic center nuclei and lead to the changes of local
      inhibitory GABAergic networks in its nuclei, resulting in the disturbances of the
      inhibitory processes in the center structures.

PMID- 25958723
TI  - [Age-related peculiarities of the hypothalamo-hypophyseo-adrenal system in
      chronic heterotypic stress].
AB  - Age-related peculiarities of the adaptation of the hypothalamo-hypophyseo-adrenal
      system (HHAS) to the effect of heterotypic stress was studied experimentally in
      the context of stress-associated behavioral reactions. Young (3 month old),
      mature (6 month old) and aging (12 month old) Sprague Dawley rats (total number
      of animals equal to 36) were exposed to chronic heterotypic stressors for 7 days
      with the subsequent testing of their behavioral responses. Histological changes
      were studied in the hypothalamus, pituitary and adrenal glands as compared to age
      matched control; immunohistochemical reactions were performed to demonstrate CRF,
      ACTH, ED1, PCNA and caspase-3 with subsequent image analysis. In the aging
      organism, as compared to young and mature animals, the degree of HHAS activation
      indicated the dissociation in its central part and adaptive desensitization
      prevention, typical to young and mature animals. Specifically, in the aging
      animals exposed to stress, high hypothalamic CRF expression was noted in
      association with relatively low hypophyseal ACTH expression and high level of
      adrenal activity. Reduced HHAS plasticity in the aging animals as compared to
      that in the other age groups, corresponded to their behavioral changes,
      demonstrating the reduced capacity of the aging organism to adapt to the exposure
      of unpredictably changing stressors.

PMID- 25958724
TI  - [Topography, relations and transformation of lumbar lymphatic sacs].
AB  - The peculiarities of the structure, skeletotopy, and syntopy of the lumbar
      lymphatic collector were studied on 20 5-8 week-old embryos and on 80 9-36 week
      old fetuses using a complex macro-microscopic method. It is found that the lumbar
      lymphatic collector in fetuses at 9-10 weeks was represented by retroperitoneal
      and retroaortic lymphatic sacs that had a fusion mode of formation and were
      interconnected. Retroperitoneal sac was located in the projection of L(I)-L(IV)
      and was in contact with the anterior surface of the abdominal aorta and inferior
      vena cava, aortic lumbar paraganglia, abdominal aortic plexus and ganglia of
      sympathetic trunk. Retroaortic sack at L(I)-L(II) was adjacent to posterior
      surface of the aorta, the lumbar vertebrae and the medial crus of the diaphragm.
      These topical relations were preserved throughout the whole fetal period.
      However, in fetuses of 11-13 weeks lymphatic sacs formed the lymphatic plexuses,
      while in fetuses of 14-36 weeks they formed lumbar lymph nodes and their
      interconnecting vessels.

PMID- 25958725
TI  - [Age-related peculiarities of thymus reaction to the exposure to helium-neon
      laser and injured muscle alloplasty with the muscle tissue from the animals of
      the same age].
AB  - Histological, cytological and morphometric changes in the thymus of 1 month-old,
      adult (3-4 months-old) and old (24-30 months-old) rats (24 animals in each group)
      were studied during muscle regeneration after the alloplasty of the injured area
      with the muscle tissue from the animal of the same age. Muscles of the donor or
      recipient were subjected to the course of preliminary irradiation with He-Ne
      laser (dose: 4.5-5.4 J/cm2 for each extremity; total dose of 9.0-10.8 J/cm2 per
      animal). It was shown that the exposure of gastrocnemius muscles that were
      prepared for the operation to He-Ne laser radiation decreased morpho-functional
      activity of the thymus in young, adult and old recipient rats the before surgery.
      This was demonstrated by its weaker reaction to the allograft during the early
      time intervals after surgery. The observed effect was more pronounced with the
      increasing age of an animal.

PMID- 25958726
TI  - [Changes in the mucous membranes of the oral cavity in chronic renal failure
      (experimental study)].
AB  - Methods of light microscopy were used to study the morphological changes of the
      oral cavity mucosa in rats (n = 48) in chronic renal failure (CRF) of various
      degrees. It was found that after 6 months of modeling of mild and moderate CRF,
      lamina propria of the oral cavity mucous membranes was diffusely infiltrated with
      leukocytes. At the same time, relative density of the distribution of the
      components of blood and lymphatic vascular bed was increased. In severe CRF, the
      atrophy and hyperkeratosis of the epithelium of the oral cavity mucous membrane
      developed, while the lamina propria demonstrated sclerosis and significant
      increase of leukocyte (primarily neutrophil and monocyte) and macrophage
      numerical density with the formation of small leukocyte infiltrates. In addition,
      in moderate and severe CRF, the number of eosinophils and plasma cells was
      increased in the lamina propria which indicates the possible presence of allergic
      component in the initiation and maintenance of its inflammation.

PMID- 25958727
TI  - [Age-related peculiarities of mast cell distribution in human esophagus wall].
AB  - Mast cells (MCs) were studied quantitatively and qualitatively in the wall of the
      esophagus (upper, middle and lower portions) of the individuals in the I period
      of mature age (22-35 years, n = 6) as well as in old and senile persons (61-82
      years, n = 10). In all the individuals, the total number of MCs was found to
      increase from the upper portion of the esophagus towards the lower one. Within
      the esophageal wall, the total number of MCs decreased in the direction from
      tunica mucosa towards adventitia. During I period of mature age, the resting MCs
      filled with granules predominated, while the degranulating MCs were located in
      the lower esophageal segment. In the individuals of old and senile age, the
      degranulating MCs were more frequently observed in the upper and lower esophageal
      segments.

PMID- 25958728
TI  - [Morpho-functional changes in the liver and the possibility of their correction
      in the offspring of rats with cholestasis].
AB  - The study aims to clarify the influence of experimental cholestasis mother on the
      structure of the liver of young rats in early postnatal development (Day 2) and
      to explore the possibility of the correction of these disturbances with Ursofalk
      drug. Material was obtained from 30 outbred albino rat pups and studied using
      histological, histochemical, morphometric and electron microscopic methods. It
      was found that under the influence of maternal cholestasis, the liver of the
      offspring demonstrated the dilation of sinusoidal capillaries, the decreased
      activity of succinate dehydrogenase and increased activity of NADH dehydrogenase
      in hepatocyte cytoplasm, the development of significant ultrastructural
      abnormalities (disappearance of lipid droplets, accentuated heterogeneity of
      mitochondrial size and shape, increased number of lysosomes). The application of
      Ursofalk partially restored hepatocyte structure and metabolism.

PMID- 25958729
TI  - [Juxtaglomerular blood flow pathway in the kidney (comparative-anatomical and age
      related aspects)].
AB  - To observe the formation of blood flow in the juxtaglomerular pathway in
      comparative-anatomical and age-related aspects, 484 kidneys from the
      representatives of the five classes of vertebrates, 50 kidneys of human fetuses
      and 193 kidneys of normal individuals of different ages were studied. Macro
      microscopic, histological and morphometric methods were used. In all the
      mammalian animal species, the significant development of vascular glomeruli and
      peritubular capillaries was observed. In human kidneys, the relative content of
      cortical and medullary arterial vessels was maximal in juvenile age. With age,
      this parameter was found to decrease both in renal cortex and medulla. The
      differentiation of renal tissue into the cortex and the medulla, that began in
      birds and was finally formed in mammals, explains the appearance of cortical and
      juxtamedullary blood flow pathways. During the antenatal period of human
      development, renal juxtaglomerular pathway of blood flow prevails over the
      cortical one. The diminished significance of juxtamedullary pathway of blood flow
      in elderly and senile age determines the decreased adaptive capacities of
      intraorgan renal arterial bed in the norm.

PMID- 25958730
TI  - [Healing of experimental defect in a long bone after implantation of "CollapAn"
      osteoplastic material in its cavity (computed tomographic study)].
AB  - The dynamics of biodegradation of "CollapAn" osteoplastic material was studied
      after its implantation into the defect of the femoral diaphysis in 30 rats.
      Computed tomographic analysis of the healing of bone defects was conducted with
      the determination of the optical density of bone tissue in Hounsfield units.
      Since Day 30 of the experiment, the appearance and further progress of the
      radiographic signs of bone tissue neoformation and maturation were noted exactly
      along the contours of osteoplastic material, together with the gradual
      disappearance of the defect from the side of bone cortical layer and simultaneous
      increase of the optical density of the intermediary and endosteal part of the
      regenerate. At Day 120, regenerate optical density exceeded the absolute optical
      density of the parent bone; simultaneously, during this period no full recovery
      of the original shape of the bone took place, while parent bone rarefication was
      identified during all the periods of observation.

PMID- 25958731
TI  - [Remodeling of the articular cartilage during the replacement of its defect by a
      biocomposite material].
AB  - The regenerative capacity of articular cartilage was studied in animals in which
      its defects were replaced by biocomposite materials based on polycaprolactone in
      combination with hydroxyapatite. Six specimens of the material were used, which
      consisted of different proportions of these polymers. In the experiment on sheep
      (n = 6) it was found that these biocomposite materials were replaced by hyaline
      like cartilage during healing of artificially created defects in the articular
      cartilage of the knee joint, while the ratio of composite components had no
      effect on the quality of the regenerates formed. These results support the view
      of a possible application of biocomposite materials in the treatment of
      degenerative and traumatic lesions of hyaline cartilage.

PMID- 25958732
TI  - [The effect of implantation of mineralized bone matrix on the regeneration of
      articular cartilage].
AB  - The peculiarities of regeneration of knee articular cartilage were studied
      experimentally in adult Wistar rats (n = 25) using the methods of optical and
      electron microscopy, histochemistry and x-ray electron probe microanalysis after
      modeling marginal perforated defect and implantation of granulated mineralized
      bone matrix (MBM) into the damaged zone. This biomaterial was demonstrated to
      have marked chondroinductive properties, to provide prolonged activation of
      reparative process, accelerated organotypical remodeling and restoration of the
      damaged articular cartilage. The data obtained indicate the possibility of MBM
      application in clinical practice for the treatment of injuries and diseases of
      the articular cartilage.

PMID- 25958734
TI  - [A synaptic marker synaptophysin].
AB  - The review summarizes the current data on synaptophysin (SYP), its functional
      role in the cell and the use of SYP immunocytochemistry for labeling the synaptic
      contacts. SYP is a transmembrane glycoprotein found in small presynaptic vesicles
      of the nerve cells and in microvesicles of the neuroendocrine cells. Literature
      data and the authors' own experience suggest that currently SYP is an important
      synaptic marker, which allows, with the use of light and confocal laser
      microscopy, to obtain the reliable data on the morphological organization of the
      synaptic structures in the central nervous system. It is also indispensable in
      the study of the efferent innervation of the internal organs. Applicatioin of the
      quantitative analysis of SYP-immunopositive structures using light and confocal
      laser microscopy allows to solve some problems that previously could be solved
      only by using electron microscopy.

PMID- 25958733
TI  - [Simultaneous demonstration of glutamate decarboxylase and synaptophysin in
      paraffin sections of rat cerebellum].
AB  - The article presents highly reproducible and inexpensive protocol for
      simultaneous demonstration of glutamate decarboxylase (GAD67), the key enzyme of
      gamma-aminobutyric acid (GABA) synthesis and synaptophysin (SYP), a marker
      protein of synaptic vesicles using confocal laser microscopy. In the cerebellar
      cortex, GAD labels Purkinje cells and pinceaux in their basal parts and is
      unevenly distributed in the neuropil of molecular and granular layers. SYP
      clearly marks the contours of large dendrites of Purkinje cells in molecular
      layer, while in the granular layers it labels parts of cerebellar glomeruli--the
      terminals of the mossy fibers. GAD-immunopositive structures (GABA-ergic axons of
      stellate cells--Golgi cells) are often located at periphery of the glomeruli. In
      the peripheral zone of the glomeruli, colocalization of GAD- and SYP
      immunopositive structures was observed, suggesting the presence of GABA-ergic
      synapses in this zone.

PMID- 25958735
TI  - [D-cells of the gastroenteropancreatic system: development, structure, function
      and regeneration (history and current state of the problem)].
AB  - The present review summarizes the literature data and the results of authors' own
      research on the development, structure, function and regeneration of D
      endocrinocytes of gastroenteropancreatic (GEP) system. The history of the
      research of these cells is reviewed and its current state of the problem is
      discussed. The information on the difference of somatostatin-producing D
      endocrinocytes from other types of endocrine cells of GAP system is presented,
      namely, the prevalence of these cells in all the organs of the digestive system
      (stomach, small and large intestine, pancreas) and other systems of the body, the
      peculiarities of their structure and regeneration in various species of
      vertebrate animals and humans in embryonic development, under conditions of
      normal functioning and in various types of pathology. On the basis of the data on
      the early differentiation of D-endocrinocytes and their secretion of hormones
      during embryonic development, structure, cytophysiology and relationships within
      the general endocrinocyte population, it is suggested that D-endocrinocytes play
      an important role in the morpho-functional state of GEP system.

PMID- 25958736
TI  - [In memory of Dmitriy Alekseyevich MOSHKOV].

PMID- 25958737
TI  - [In memory of Georgiy Silvestrovich KATINAS].

PMID- 25958738
TI  - [In memory of Nikolai Vasiliyevich YAMSHIKOV].

PMID- 25958739
TI  - [In memory of Gennadiy Mikhailovich SEMYONOV].

PMID- 25958742
TI  - New Arab family with cerebral dysgenesis, neuropathy, ichthyosis and keratoderma
      syndrome suggests a possible founder effect for the c.223delG mutation.

PMID- 25958740
TI  - Understanding the role of haptoglobin in psoriasis: effects of ultraviolet B.
AB  - BACKGROUND: Haptoglobin (Hp) is one of the acute phase proteins, whose main
      function is to bind free haemoglobin (Hb) and transport it to the liver for
      degradation and iron recycling. In addition to its role as an Hb scavenger, Hp
      has been shown to behave as an anti-inflammatory, antioxidant and angiogenic
      factor. We previously investigated the role of Hp in the pathogenesis of
      psoriasis, and found that it displays some structural modifications that might be
      associated with protein function in the disease. Phototherapy is an efficacious
      treatment for psoriasis, although the biological mechanisms by which phototherapy
      improves psoriasis are still unclear. AIM: To investigate the effects of
      ultraviolet (UV)B on Hp to clarify the role of Hp in psoriasis. METHODS:
      Expression of the genes encoding Hp, interleukin (IL)-6 and IL-10 was assessed in
      UVB-irradiated and unirradiated HaCaT cells. The biological significance of Hp
      modulation of UVB treatment was confirmed by ELISA and Western blotting. The Hp
      gene and protein expression in the skin of patients with psoriasis was also
      investigated. RESULTS: In vitro results showed that UVB modulated IL-6 and IL-10
      gene expression and Hp gene and protein expression in HaCaT cells. The in vivo
      data also showed that Hp levels were increased in the skin of patients with
      psoriasis compared with healthy controls. CONCLUSIONS: UVB irradiation was able
      to modulate Hp production in immortalized keratinocytes. The higher levels of Hp
      in vivo in both lesional and nonlesional skin suggest that it might have a role
      in the pathogenesis of the disease.

PMID- 25958743
TI  - An atypical addition to the chemokine receptor nomenclature: IUPHAR Review 15.
AB  - Chemokines and their receptors are essential regulators of in vivo leukocyte
      migration and, some years ago, a systematic nomenclature system was developed for
      the chemokine receptor family. Chemokine receptor biology and biochemistry was
      recently extensively reviewed. In this review, we also highlighted a new
      component to the nomenclature system that incorporates receptors previously known
      as 'scavenging', or 'decoy', chemokine receptors on the basis of their lack of
      classical signalling responses to ligand binding and their general ability to
      scavenge, or sequester, their cognate chemokine ligands. These molecules are now
      collectively referred to as 'atypical chemokine receptors', or ACKRs, and play
      fundamental roles in regulating in vivo responses to chemokines. This commentary
      highlights this new addition to the chemokine receptor nomenclature system and
      provides brief information on the four receptors currently covered by this
      nomenclature. 

PMID- 25958744
TI  - Should we abstain from treating women with endometriosis using menopausal hormone
      therapy, for fear of an increased ovarian cancer risk?
AB  - Women suffering from endometriosis often have an early menopause, resulting in
      severe menopausal symptoms and an increased risk of osteoporosis. They are
      therefore candidates for menopausal hormone therapy (MHT). Unfortunately, MHT may
      increase the risk of endometriosis recurrence. Moreover, endometriosis patients
      are at increased risk of ovarian cancer, which may be further enhanced by MHT
      use. It is unknown, however, whether MHT more frequently increases type I (low
      grade serous tumors), which seem to be increased when endometriosis is present,
      or type II (the more aggressive high-grade serous) tumors. We propose the
      following decision-making algorithm for endometriosis patients considering MHT.
      Those who have been treated with bilateral salpingo-oophorectomy, and in whom
      there is no residual endometriotic disease, can probably be treated using MHT
      without risk of endometriosis recurrence or fear of ovarian cancer. For women
      with significant, residual endometriosis lesions, the benefit may outweigh the
      risks, when menopause is reached before the age of 45 years or when severe
      symptoms are present. 

PMID- 25958745
TI  - [Being a medical doctor and a scientist, a constantly evolving challenge].

PMID- 25958746
TI  - [Compartimentalization of immune responses in the mosquito Anopheles gambiae:
      consequences for insect vector immunity research].

PMID- 25958747
TI  - [The intestinal microbiota helps shapping the adaptive immune response against
      viruses].

PMID- 25958748
TI  - [The hepatocyte is the only stem cell in the liver].

PMID- 25958749
TI  - [Follicular lymphoma: a history of perversion of immunological memory].

PMID- 25958750
TI  - [Smartphone use shapes cortical tactile sensory processing from the fingertips].

PMID- 25958751
TI  - [A circannual clock wakes up hibernating mammals].

PMID- 25958752
TI  - [Detecting life thanks to the atomic force microscope].

PMID- 25958753
TI  - [Ecological and evolutionary approaches are essential to understand better the
      epidemics of avian influenza].

PMID- 25958754
TI  - [New insights to prevent preterm labor].

PMID- 25958755
TI  - [IFITM, a common barrier to many viruses].
AB  - During evolution, organisms developed adaptative mechanisms to survive continuous
      aggressions from a variety of pathogens. Among these lines of defence, many
      cellular proteins have been described to modulate viral replication and are the
      subject of intense study. This review will focus on IFITM (interferon induced
      transmembrane protein), a family of proteins that act against a particularly wide
      range of viruses. We will summarize our knowledge of the antiviral mechanisms
      used by IFITM to interfere with the replication of several viruses, and more
      specifically HIV (human immunodeficiency virus). 

PMID- 25958756
TI  - [Toward an explanation for the mnemonic effects of glucocorticoids?].
AB  - If the engram of long-term memory is encoded by structural changes of neuronal
      circuits, they are expected to be present at distant time points after learning,
      to be specific of circuits activated by learning, and sensitive to behavioral
      contingencies. In this review we present new concepts that emerged from in vivo
      imaging studies that tracked the structural bases of the memory trace. A fine
      balance of spine formation and spine elimination needed for behavioral adaptation
      to new experience is regulated by glucocorticoids, which are secreted in
      synchrony with circadian rhythms and in response to stress. Disruption of
      glucocorticoid oscillations frequently observed in psychiatric disorders like
      depression and post-traumatic stress produces spine turnover defects and learning
      disabilities. These new findings provide a new framework for explaining the
      potent but complex mnemonic effects of glucocorticoids. 

PMID- 25958757
TI  - [Genetic alterations in primary aldosteronism].
AB  - Primary aldosteronism (PA) is the most frequent form of arterial hypertension. It
      is caused in the majority of cases by an aldosterone producing adenoma (APA) of
      the adrenal cortex or by bilateral adrenal hyperplasia. Recent advances have
      allowed to identify a certain number of genetic abnormalities involved in the
      development of APA or responsible for familial forms of PA. These findings have
      highlighted the central role of calcium signaling in this process. In this review
      we will discuss the genetic defects associated with PA and discuss the mechanisms
      whereby they lead to increased aldosterone production and cell proliferation. The
      possible consequences that this knowledge will have on the diagnosis and
      management of PA will be addressed. 

PMID- 25958758
TI  - [Role of brain lipid sensing in nervous regulation of energy balance].
AB  - Fatty acid sensitive neurons located in hypothalamus, hippocampus or striatum are
      able to detect daily variations of plasma fatty acid levels. Thus, these neurons
      play a role to regulate energy balance by controling food intake, insulin
      secretion or hepatic glucose production. Molecular mechanisms that mediate fatty
      acid effects include receptor FAT (fatty acid transporter)/CD36. Deregulation of
      this brain lipid sensing may be an early event leading to further dysfunction of
      energy balance leading to obesity and type 2 diabetes. 

PMID- 25958759
TI  - [Therapeutic potential of optogenetic neuromodulation].
AB  - Optogenetic neuromodulation techniques, which have emerged during the last 15
      years, have considerably enhanced our ability to probe the functioning of neural
      circuits by allowing the excitation and inhibition of genetically-defined
      neuronal populations using light. Having gained tremendous popularity in the
      field of fundamental neuroscience, these techniques are now opening new
      therapeutic avenues. Optogenetic neuromodulation is a method of choice for
      studying the physiopathology of neurological and neuropsychiatric disorders in a
      range of animal models, and could accelerate the discovery of new therapeutic
      strategies. New therapeutic protocols employing optogenetic neuromodulation may
      also emerge in the near future, offering promising alternative approaches for
      disorders which lack appropriate treatments, such as pharmacoresistant epilepsy
      and inherited retinal degeneration. 

PMID- 25958760
TI  - [The French National Compound Library: advances and future prospects].
AB  - The French National Compound Library (Chimiotheque Nationale) has been created in
      2003 and is the federation of local collections. It contains more than 56 000
      small molecules and natural compounds synthesised or isolated in different
      laboratories over the past years. This explains the diversity of the collection.
      The strength of this initiative is the ability to connect chemists and biologists
      for the development of hits. This development involves the synthesis of analogues
      or/and chemical tools to find new targets. These collaborations lead to the
      identification of new chemical probes. These probes able to modulate a biological
      function are essential to study biological pathways. They can also be useful for
      therapeutic applications. This article will describe the major achievements and
      perspectives of the French Chemical Library. 

PMID- 25958761
TI  - [Strength and specificity of the CMBA screening platform for bioactive molecules
      discovery].
AB  - Used as powerful chemical probes in Life science fundamental research, the
      application potential of new bioactive molecular entities includes but extends
      beyond their development as therapeutic drugs in pharmacology. In this review, we
      wish to point out the methodology of chemical libraries screening on living cells
      or purified proteins at the CMBA academic platform of Grenoble Alpes University,
      and strategies employed to further characterize the selected bioactive molecules
      by phenotypic profiling on human cells. Multiple application fields are concerned
      by the screening activity developed at CMBA with bioactive molecules previously
      selected for their potential as tools for fundamental research purpose,
      therapeutic candidates to treat cancer or infection, or promising compounds for
      production of bioenergy. 

PMID- 25958762
TI  - [A genetic view of addiction].
AB  - The genetic analyses of addictions recently converted to genome-wide association
      studies (GWAS) and thanks to national and international consortia, allowed to
      recruit large cohorts of patients. This approach allowed the identification of
      the first susceptibility gene in addiction (tobacco), with genes CHRNA5, CHRNA3
      and CHRNB4 encoding the alpha5, alpha3 and b4 subunits involved in the formation
      of nicotinic receptors, explaining 14% of the attributable risk for tobacco
      dependence. Variants of ADH1B and ADH1C genes encoding alcohol dehydrogenases
      enzymes have also been consistently associated, this time with alcohol dependence
      (AD). Finally, DRD2 and ANKK1 genes, involved in the dopaminergic pathway, and
      which were initially associated with AD, are now considered to be involved in a
      broader phenotype (addiction to psychoactive substances) including opiates.
      Future directions in molecular study of addiction are gene x environment
      interactions though the epigenetic approach. Numerous studies already
      investigated the methylome in addiction, including histone and microRNA
      modifications. 

PMID- 25958763
TI  - [Epigenetics and drug addiction: a focus on MeCP2 and on histone acetylation].
AB  - Chronic drug exposure alters gene expression in the brain, which is believed to
      underlie compulsive drug seeking and drug taking behavior. Recent evidence shows
      that drug-induced long-term neuroadaptations in the brain are mediated in part by
      epigenetic mechanisms. By remodeling chromatin, this type of regulation
      contributes to drug-induced synaptic plasticity that translates into behavioral
      modifications. How drug-induced alterations in DNA methylation regulate gene
      expression is reviewed here, with a focus on MeCP2, a protein binding methylated
      DNA. The importance of histone modifications, especially acetylation is also
      discussed, with an emphasis on the effects of inhibitors of histone deacetylases
      on drug-induced behavioral changes. The precise identification of the epigenetic
      mechanisms that are under the control of drugs of abuse may help to uncover novel
      targets for the treatment of drug seeking and relapse. 

PMID- 25958764
TI  - [23 and Me: how to make (a lot of) money out of your customers].
AB  - The announcement of several deals between the DTC genetics firm 23 and Me and
      Genentech, Pfizer and other corporations reveals the real business model of the
      company: selling access to sets of characterized patients for targeted drug
      development. This may be a useful strategy, but it raises a number of questions
      concerning the privacy of the company's customers and also of adequate
      compensation when they become valuable currency.

PMID- 25958765
TI  - [The tragic side of medicine].

PMID- 25958766
TI  - Higher positive lymph node ratio indicates poorer distant metastasis-free
      survival in adenoid cystic carcinoma patients with nodal involvement.
AB  - OBJECTIVE: Extensive studies have been conducted to analyze adenoid cystic
      carcinoma (ACC) in the head and neck region. No research has been published
      focusing on ACC patients with cervical lymph node (LN) metastasis. The aims of
      current investigation were to summarize the clinical characteristics of ACC
      patients with LN metastasis (ACC-LNM) and to identify prognostic factors for
      tumor-related outcomes. MATERIAL AND METHODS: A retrospective review was
      conducted with respect to ACC patients with nodal involvement between 2000 and
      2013. The clinical variables and outcomes of these special cases were recorded
      and further analyzed. Metastasis-free survival and overall survival rate were
      calculated using the Kaplan-Meier method, and the log-rank test and Cox
      regression analysis were applied to identify the prognostic factors. RESULTS: A
      total of 47 patients (34 male and 13 female) 32-77 years of age (mean: 54.6
      years; median: 54 years) were analyzed in the current protocol. The recurrence
      free survival (RFS), distant metastasis-free survival (MFS), and overall survival
      (OS) rate in all patients were 90.1%, 55.6%, and 60.1%, respectively. In
      univariate analysis, T stage, positive LN ratio, LN-involved section, and
      extracapsular spread were strongly associated with poorer MFS rate. The
      predictive roles of LN-involved section and surgical margin on the OS rate were
      also identified. In multivariate analysis, positive LN ratio and surgical margin
      were predictors for MFS and OS rate, respectively. CONCLUSIONS: Positive LN ratio
      was strongly associated with distant metastasis. Comprehensive treatment should
      be performed in ACC patients with higher positive LN ratios. In addition, ideal
      surgical margin should be achieved to acquire better overall survival rate.

PMID- 25958767
TI  - Tooth extraction in patients receiving oral or intravenous bisphosphonate
      administration: A trigger for BRONJ development?
AB  - INTRODUCTION: Scientific debate outlines tooth extraction as a potential trigger
      for the onset of bisphosphonate-related osteonecrosis of the jaw (BRONJ).
      Therefore, the aim of this study was to investigate the outcome of tooth
      extractions in patients receiving bisphosphonate therapy. PATIENTS AND METHODS: A
      retrospective cohort study was performed on patients with a history of oral or
      intravenous bisphosphonate administration and tooth extraction between 2007 and
      2013 in a single university hospital oral and maxillofacial surgical unit. In all
      patients, extractions were performed according to the guidelines of the German
      Society of Oral and Maxillofacial Surgery. The outcome variable was the onset of
      typical BRONJ signs during postoperative follow-up. RESULTS: In 72 subjects (53
      female, 19 male; mean age 67.5 years) receiving oral (n = 27) and/or intravenous
      (n = 45) bisphosphonates due to malignant tumor (n = 43) or osteoporosis (n =
      29), 216 tooth extractions were performed. The mean duration of intake was 36.2
      months. In 67 out of 72 patients (93.1%) and 209 out of the 216 extraction sites
      the postoperative course was uneventful and the wounds healed without
      complications. Three of the 72 patients (4.2%) developed osteonecrosis of the jaw
      in four of the 216 extraction sites (1.9%). Duration and route of administration,
      oral hygiene and steroid intake were identified as potential risk factors for the
      development of BRONJ. CONCLUSION: Tooth extraction in patients receiving
      bisphosphonates can be performed in a safe and predictable way, even in high-risk
      patients, when performed according to established guidelines. It is not tooth
      extractions themselves, but rather prevailing infectious conditions that may be a
      key risk factor for the development of BRONJ.

PMID- 25958768
TI  - Absence of an association between socioeconomic indicators and traumatic dental
      injury: a systematic review and meta-analysis.
AB  - OBJECTIVE: The aim of this study was to perform a systematic review and search
      for scientific evidence on the association between socioeconomic indicators and
      traumatic dental injury (TDI) in the primary dentition. METHODOLOGY: The PubMed,
      ISI, LILACS, Cochrane Library, and Embase databases were searched for articles
      addressing possible associations between socioeconomic indicators and TDI in the
      primary teeth in journals dating from the inception of the databases through to
      December 2013. Two independent reviewers performed data extraction and analyzed
      the quality of the studies. Meta-analysis was undertaken. Pooled estimates were
      calculated with a 95% confidence interval (CI) and odds ratios (OR). RESULTS:
      Sixteen articles were included in the systematic review. Children from families
      with household income less than two times average salary (U$ 592) (OR: 0.77; 95%
      CI: 0.66-0.90) or more than three times the average salary (U$ 888) (OR: 0.76;
      95% CI: 0.65-0.89) had a significantly lower chance of having TDI in the primary
      dentition. TDI was not associated with socioeconomic status (high vs low - OR:
      0.77; 95% CI: 0.43-1.36; high vs medium - OR: 1.03; 95% CI: 0.72-1.48; medium vs
      low - OR: 0.70; 95% CI: 0.42-1.19), house ownership (owned vs rented - OR: 1.28;
      95% CI: 0.98-1.66), mother's schooling (OR: 0.89; 95% CI: 0.74-1.08), or father's
      schooling (OR: 1.01; 95% CI: 0.62-2.74). CONCLUSION: The scientific evidence
      demonstrates that socioeconomic indicators are not associated with TDI in the
      primary dentition. The evidence of an association between a low income and TDI is
      weak. In general, studies had low risk of bias. Further prospective cohort
      studies are needed to confirm this association.

PMID- 25958769
TI  - Self-hypnosis for intrapartum pain management in pregnant nulliparous women: a
      randomised controlled trial of clinical effectiveness.
AB  - OBJECTIVE: (Primary) To establish the effect of antenatal group self-hypnosis for
      nulliparous women on intra-partum epidural use. DESIGN: Multi-method randomised
      control trial (RCT). SETTING: Three NHS Trusts. POPULATION: Nulliparous women not
      planning elective caesarean, without medication for hypertension and without
      psychological illness. METHODS: Randomisation at 28-32 weeks' gestation to usual
      care, or to usual care plus brief self-hypnosis training (two * 90-minute groups
      at around 32 and 35 weeks' gestation; daily audio self-hypnosis CD). Follow up at
      2 and 6 weeks postnatal. MAIN OUTCOME MEASURES: Primary: epidural analgesia.
      Secondary: associated clinical and psychological outcomes; cost analysis.
      RESULTS: Six hundred and eighty women were randomised. There was no statistically
      significant difference in epidural use: 27.9% (intervention), 30.3% (control),
      odds ratio (OR) 0.89 [95% confidence interval (CI): 0.64-1.24], or in 27 of 29
      pre-specified secondary clinical and psychological outcomes. Women in the
      intervention group had lower actual than anticipated levels of fear and anxiety
      between baseline and 2 weeks post natal (anxiety: mean difference -0.72, 95% CI 
      1.16 to -0.28, P = 0.001); fear (mean difference -0.62, 95% CI -1.08 to -0.16, P
      = 0.009) [Correction added on 7 July 2015, after first online publication: 'Mean
      difference' replaced 'Odds ratio (OR)' in the preceding sentence.]. Postnatal
      response rates were 67% overall at 2 weeks. The additional cost in the
      intervention arm per woman was L4.83 (CI -L257.93 to L267.59). CONCLUSIONS:
      Allocation to two-third-trimester group self-hypnosis training sessions did not
      significantly reduce intra-partum epidural analgesia use or a range of other
      clinical and psychological variables. The impact of women's anxiety and fear
      about childbirth needs further investigation.

PMID- 25958770
TI  - Prevalence of cryptococcal antigenuria at initial HIV diagnosis in KwaZulu-Natal.
AB  - OBJECTIVES: The World Health Organization (WHO) recommends screening HIV-infected
      people for cryptococcal antigens to identify cryptococcosis, a major cause of
      AIDS-related deaths. As the burden of cryptococcosis is unknown in South Africa's
      KwaZulu-Natal province, we assessed the cryptococcal antigenuria prevalence among
      newly diagnosed HIV-infected adults there. METHODS: We conducted a cross
      sectional study of newly diagnosed HIV-infected adults who received voluntary HIV
      testing in an out-patient clinic. Participants provided a urine specimen in a
      sterile container, and we performed testing with a WHO-endorsed rapid
      cryptococcal antigen lateral flow assay (Immy Inc., Norman, OK, USA) per the
      manufacturer's specifications. We assessed cryptococcal antigenuria prevalence
      among participants with CD4 counts < 200 cells/MUL, and stratified results by CD4
      count categories. RESULTS: Among 432 participants, the mean (+/- standard
      deviation) age was 36.1 +/- 9.9 years and 172 (40%) were female. The overall
      estimated prevalence of cryptococcal antigenuria was 9.0% [95% confidence
      interval (CI) 6.5-12.1%]. CD4 counts were available for 319 participants (74%);
      the median CD4 count was 75 cells/MUL [interquartile range (IQR) 34-129
      cells/MUL]. Participants with a negative cryptococcal antigenuria screening test
      had a median CD4 count of 79 cells/MUL (IQR 36-129 cells/MUL), while participants
      with a positive cryptococcal test had a median CD4 count of 41 cells/MUL (IQR 10
      112 cells/MUL). The estimated prevalence of cryptococcal antigenuria among
      participants with CD4 counts < 50 cells/MUL was 12.5% (95% CI 7.0-20.1%), which
      was significantly higher than that among participants with CD4 counts of 50-200
      cells/MUL (4.8%; 95% CI 2.3-8.7%). CONCLUSIONS: Nearly 1 in 10 newly diagnosed
      HIV-infected adults with CD4 counts < 200 cells/MUL in KwaZulu-Natal had evidence
      of cryptococcal antigenuria. Point-of-care CD4 count testing and cryptococcal
      antigen screening may rapidly identify cryptococcosis at the time of HIV
      diagnosis.

PMID- 25958772
TI  - Emergency nurses perceptions of the role of family/carers in caring for
      cognitively impaired older persons in pain: a descriptive qualitative study.
AB  - BACKGROUND: On arrival to the emergency department many older persons are
      accompanied by family/carers. Yet the role of family/carers in the emergency
      department is unclear. We know very little about how emergency department nurses
      balance care practices to accommodate family/carers while specifically meeting
      the needs of cognitively impaired older persons experiencing pain. OBJECTIVES:
      The aim of this paper was to understand emergency nurses' perceptions of the role
      of family/carers in caring for the older cognitively impaired person experiencing
      pain. DESIGN: Emergency nurses were invited to participate in focus group
      interviews. A semi-structured interview tool was developed from the literature
      and comprised open-ended questions and three Likert scale items which assisted to
      focus nurses' thoughts on their perceived role of family/carers in the emergency
      department. SETTINGS: The study was undertaken across four emergency departments
      in Sydney, Australia and included two district hospitals and two tertiary
      referral hospitals. PARTICIPANTS: Emergency nurses were invited to participate in
      one face to face, focus group interview. Purposive sampling was used and
      inclusion criteria included at least one year emergency department experience.
      METHODS: Interview data were analysed and organised thematically. Two expert
      qualitative researchers independently reviewed transcripts and emerging coding
      and interpretation. RESULTS: Eighty nurses participated in 16 focus group
      interviews across four hospitals. Participating nurses included 67 (84%) females
      and 13 (16%) males with 8.6 years (mean; SD +/-8.64) experience in the emergency
      department. Three key themes relating to family/carers emerged from the analysis.
      The themes included (i) the role of families and carers in building a clinical
      picture; (ii) family and carers as a hidden workforce; and (iii) family and carer
      roles in pain management decision making. CONCLUSIONS: The study has provided
      insight into the role of family/carers as perceived by emergency nurses. There
      were many benefits in partnering with family/carers when information gathering on
      the older cognitively impaired person in pain. Family/carers are sensitive to
      health behaviour changes of older cognitively impaired people, which can assist
      nurses to optimise pain management.

PMID- 25958771
TI  - Novel triterpenoid saponins from residual seed cake of Camellia oleifera Abel.
      show anti-proliferative activity against tumor cells.
AB  - Four oleanane-type triterpenoid saponins were isolated from the seed cake of
      Camellia oleifera Abel.: camelliasaponin B1 and three new saponins,
      oleiferasaponin C1-C3 (1-3). Their structures were identified as 22-O-angeloyl
      camelliagenin B 3-O-[beta-d-galactopyranosyl-(1->2)]-[beta-d-galactopyranosyl-(1
      >2)-alpha-l-arabinopyranosyl-(1->3)]-beta-d-glucopyranosiduronic acid methyl
      ester (1); 22-O-angeloyl-camelliagenin A 3-O-[beta-d-galactopyranosyl-(1->2)]
      [beta-d-glucopyranosyl-(1->2)-beta-d-galactopyranosyl-(1->3)]-beta-d
      glucopyranosiduronic acid methyl ester (2); and 28-O-cinnamoyl-camelliagenin B 3
      O-[beta-d-galactopyranosylz-(1->2)] [beta-d-galactopyranosyl(1->2)-alpha-l
      arabinopyranosyl-(1->3)]-beta-d-glucopyranosiduronic acid methyl ester (3)
      through 1D and 2D NMR, HR-ESI-MS, as well as GC-MS spectroscopic methods. The
      anti-proliferative activities of these four compounds were investigated on five
      human tumor cell lines (BEL-7402, BGC-823, MCF-7, HL-60 and KB). Compounds 1 and
      2 and camelliasaponin B1 showed significant cytotoxic activities. 

PMID- 25958773
TI  - Prevalence of and risk factors for binge eating behaviour in 6930 adults starting
      a weight loss or maintenance programme.
AB  - OBJECTIVE: Conflicting data are available on the prevalence of binge eating
      behaviour (BE) in individuals seeking to lose or maintain weight. The present
      study aimed to estimate the prevalence of and the risk factors for BE in a large
      sample of men and women starting a weight loss or maintenance programme. DESIGN:
      Cross-sectional study. BE was defined as a Binge Eating Scale (BES) score >=18.
      The State-Trait Anxiety Inventory and the Italian Depression Questionnaire were
      used to assess anxiety and depression. Besides sex, age and BMI, marital status,
      educational level, smoking and physical activity were evaluated as potential risk
      factors for BE. Uni- and multivariable Poisson working regression models were
      used to estimate prevalence ratios (PR) and marginal probabilities. SETTING:
      Nutritional research centre. SUBJECTS: Adults (n 6930; 72 % women) with a median
      age of 46 years (range 18-81 years) were consecutively studied. RESULTS: BE
      prevalence in the pooled sample was 17 %. At multivariable analysis, being a
      woman (PR=2.70), smoking (PR=1.15) and increasing BMI (PR=1.05 for 1 kg/m(2)
      increase) were risk factors for BE. On the contrary, being older (PR=0.99 for 1
      year increase), performing physical activity (PR=0.89) and being married
      (PR=0.88) were protective factors for BE. Anxiety and depression were more common
      in subjects with BE. CONCLUSIONS: BE is common in individuals seeking to lose or
      maintain weight. The prevalence of BE is higher in young obese women. However, BE
      is present also in men, elders and normal-weight subjects.

PMID- 25958774
TI  - Magnolia officinalis bark extract, a recently identified contact allergen in
      'anti-ageing' cosmetics.

PMID- 25958775
TI  - Melatonin regulates carbohydrate metabolism and defenses against Pseudomonas
      syringae pv. tomato DC3000 infection in Arabidopsis thaliana.
AB  - Melatonin has been reported to promote plant growth and development. Our
      experiments with Arabidopsis thaliana showed that exogenous applications of this
      molecule mediated invertase inhibitor (C/VIF)-regulated invertase activity and
      enhanced sucrose metabolism. Hexoses were accumulated in response to elevated
      activities by cell wall invertase (CWI) and vacuolar invertase (VI). Analyses of
      sugar metabolism-related genes revealed differential expression during plant
      development that was modulated by melatonin. In particular, C/VIF1 and C/VIF2
      were strongly down-regulated by exogenous feeding. We also found the elevated CWI
      activity in melatonin-treated Arabidopsis improved the factors (cellulose,
      xylose, and galactose) for cell wall reinforcement and callose deposition during
      Pseudomonas syringae pv. tomato DC3000 infection, therefore, partially induced
      the pathogen resistance. However, CWI did not involve in salicylic acid (SA)
      regulated defense pathway. Taken together, this study reveals that melatonin
      plays an important role in invertase-related carbohydrate metabolism, plant
      growth, and pathogen defense. 

PMID- 25958776
TI  - Lean Six Sigma: a new approach to the management of patients undergoing
      prosthetic hip replacement surgery.
AB  - RATIONALE, AIMS AND OBJECTIVES: In 2012, health care spending in Italy reached
      ?114.5 billion, accounting for 7.2% of the Gross Domestic Product (GDP) and 14.2%
      of total public spending. Therefore, reducing waste in health facilities could
      generate substantial cost savings. The objective of this study is to show that
      Lean Six Sigma represents an appropriate methodology for the development of a
      clinical pathway which allows to improve quality and to reduce costs in
      prosthetic hip replacement surgery. METHODS: The methodology used for the
      development of a new clinical pathway was Lean Six Sigma. Problem solving in Lean
      Six Sigma is the DMAIC (Define, Measure, Analyse, Improve, Control) roadmap,
      characterized by five operational phases which make possible to reach fixed goals
      through a rigorous process of defining, measuring, analysing, improving and
      controlling business problems. RESULTS: The following project indicated several
      variables influencing the inappropriate prolongation of the length of stay for
      inpatient treatment and corrective actions were performed to improve the
      effectiveness and efficiency of the process of care. The average length of stay
      was reduced from 18.9 to 10.6 days (-44%). CONCLUSION: This article shows there
      is no trade-off between quality and costs: Lean Six Sigma improves quality and,
      at the same time, reduces costs.

PMID- 25958777
TI  - The Power and the Peril of Large Administrative Databases.

PMID- 25958778
TI  - Differential dielectric responses of chondrocyte and Jurkat cells in
      electromanipulation buffers.
AB  - Electromanipulation of cells as a label-free cell manipulation and
      characterization tool has gained particular interest recently. However, the
      applicability of electromanipulation, particularly dielectrophoresis (DEP), to
      biological cells is limited to cells suspended in buffers containing lower
      amounts of salts relative to the physiological buffers. One might question the
      use of low conductivity buffers (LCBs) for DEP separation, as cells are stressed
      in buffers lacking physiological levels of salt. In LCB, cells leak ions and
      undergo volume regulation. Therefore, cells exhibit time-dependent DEP response
      in LCB. In this work, cellular changes in LCB are assessed by dielectric
      spectroscopy, cell viability assay, and gene expression of chondrocytes and
      Jurkats. Results indicate leakage of ions from cells, increases in cytoplasmic
      conductivity, membrane capacitance, and conductance. Separability factor, which
      defines optimum conditions for DEP cell separation, for the two cell types is
      calculated using the cellular dielectric data. Optimum DEP separation conditions
      change as cellular dielectric properties evolve in LCB. Genetic analyses indicate
      no changes in expression of ionic channel proteins for chondrocytes suspended in
      LCB. Retaining cellular viability might be important during dielectrophoretic
      separation, especially when cells are to be biologically tested at a downstream
      microfluidic component. 

PMID- 25958779
TI  - Severe osteomalacia mimicking progressive myopathy.

PMID- 25958781
TI  - Parallel evolution in an invasive plant: effect of herbivores on competitive
      ability and regrowth of Jacobaea vulgaris.
AB  - A shift in the composition of the herbivore guild in the invasive range is
      expected to select for plants with a higher competitive ability, a lower regrowth
      capacity and a lower investment in defence. We show here that parallel evolution
      took place in three geographically distinct invasive regions that differed
      significantly in climatic conditions. This makes it most likely that indeed the
      shifts in herbivore guilds were causal to the evolutionary changes. We studied
      competitive ability and regrowth of invasive and native Jacobaea vulgaris using
      an intraspecific competition set-up with and without herbivory. Without
      herbivores invasive genotypes have a higher competitive ability than native
      genotypes. The invasive genotypes were less preferred by the generalist Mamestra
      brassicae but more preferred by the specialist Tyria jacobaeae, consequently
      their competitive ability was significantly increased by the first and reduced by
      the latter. Invasive genotypes showed a lower regrowth ability in both herbivore
      treatments. 

PMID- 25958783
TI  - Continuous crafting of uniform colloidal nanocrystals using an inert-gas-driven
      microflow reactor.
AB  - Recent research has witnessed rapid advances in synthesis of nanocrystals, which
      has led to the development of a large variety of approaches for producing
      nanocrystals with controlled dimensions. However, most of these techniques lack
      the high-throughput production. Herein, we report on a viable and robust strategy
      based on an inert-gas-driven microflow reactor for continuous crafting of high
      quality colloidal nanocrystals. With the judicious introduction of the inert-gas
      driven capability, the microflow reactor provides an attractive platform for
      continuous production of colloidal nanocrystals in large quantities, including
      easily-oxidized nanocrystals. The as-synthesized nanocrystals possessed a uniform
      size and shape. Intriguingly, the size of nanocrystals can be effectively
      tailored by varying the flow rate and the precursor concentration. We envision
      that the microflow reactor strategy is general and offers easy access to a wide
      range of scalable nanocrystals for potential applications in sensors, optics,
      optoelectronics, solar energy conversion, batteries, photocatalysis, and
      electronic devices. 

PMID- 25958782
TI  - High efficacy of a 20 amino acid peptide of the acidic ribosomal protein P0
      against the cattle tick, Rhipicephalus microplus.
AB  - Current strategies to control cattle ticks use integrated control programs (ICP)
      that include vaccination. Reduction in the use of chemicals and in the cost of
      tick control, the delay or elimination of acaricide resistance and the decreasing
      of environmental pollution are the advantages of using these programs. This
      integrated program is potentially applicable to all genotypes of chemical
      resistant ticks. However, the problem here is to improve the efficacy of anti
      tick vaccines. The P0 protein is a structural component of the ribosome of all
      organisms. We have identified an immunogenic region of ribosomal protein P0 from
      Rhipicephalus spp. ticks that is not very conserved compared to the orthologous
      protein in their hosts. A synthetic 20 amino acid peptide from this sequence was
      effective as a vaccine against Rhipicephalus sanguineus infestations in an
      immunization and challenge experiment using rabbits. In this paper, the same
      peptide used as vaccine against the cattle tick Rhipicephalus Boophilus microplus
      shows a significant diminution in the number of engorged females recovered, in
      the weight of females and the weight of egg masses. The number of eggs hatched
      was also significantly reduced for the vaccinated group, with an overall
      effectivity for the antigen pP0 of 96%. These results, together with the
      conserved sequence of the P0 peptide among ticks, suggest that this antigen could
      be a good broad spectrum vaccine candidate. It would be expected to be active
      against many species of ticks and thus has promise in an ICP for effective
      control of ticks and thereby to improve the efficiency and productivity of the
      livestock industry. 

PMID- 25958780
TI  - Migration-related phenotypic divergence is associated with epigenetic
      modifications in rainbow trout.
AB  - Migration is essential for the reproduction and survival of many animals, yet
      little is understood about its underlying molecular mechanisms. We used the
      salmonid Oncorhynchus mykiss to gain mechanistic insight into smoltification,
      which is a morphological, physiological and behavioural transition undertaken by
      juveniles in preparation for seaward migration. O. mykiss is experimentally
      tractable and displays intra- and interpopulation variation in migration
      propensity. Migratory individuals can produce nonmigratory progeny and vice
      versa, indicating a high degree of phenotypic plasticity. One potential way that
      phenotypic plasticity might be linked to variation in migration-related life
      history tactics is through epigenetic regulation of gene expression. To explore
      this, we quantitatively measured genome-scale DNA methylation in fin tissue using
      reduced representation bisulphite sequencing of F2 siblings produced from a cross
      between steelhead (migratory) and rainbow trout (nonmigratory) lines. We
      identified 57 differentially methylated regions (DMRs) between smolt and resident
      O. mykiss juveniles. DMRs were high in magnitude, with up to 62% differential
      methylation between life history types, and over half of the gene-associated DMRs
      were in transcriptional regulatory regions. Many of the DMRs encode proteins with
      activity relevant to migration-related transitions (e.g. circadian rhythm
      pathway, nervous system development, protein kinase activity). This study
      provides the first evidence of a relationship between epigenetic variation and
      life history divergence associated with migration-related traits in any species.

PMID- 25958784
TI  - The Swedish uterus transplantation project: the story behind the Swedish uterus
      transplantation project.

PMID- 25958785
TI  - Health screening to identify opportunities to improve preventive medicine in cats
      and dogs.
AB  - OBJECTIVES: To describe the results of a prevention campaign in terms of
      participation and pet health status and to identify opportunities to improve
      preventive medicine in cats and dogs. METHODS: An awareness campaign was designed
      to highlight the role of veterinarians and emphasise the benefits of a veterinary
      visit. Owners were invited to make an appointment for a free pet health check in
      a voluntarily participating veterinary clinic. Observations recorded by the
      veterinarians were entered in a database and subsequently analysed using simple
      descriptive statistics. RESULTS: A total of 5305 completed health check forms
      were analysed. The percentages of overweight and obese dogs and cats were 34 and
      36%, respectively; this was the most common finding, followed by dental calculus
      (31% in dogs, 21% in cats). In total 67% of cats did not undergo flea control and
      59% were not vaccinated. CLINICAL SIGNIFICANCE: Opportunities for increased
      quality of care are numerous given the high percentage of intact, unvaccinated or
      non-permanently identified pets and the low level of worm and flea control.
      Animal health should benefit from preventive measures, and improved management
      can be undertaken after early detection of diseases.

PMID- 25958786
TI  - Impact of dataset diversity on accuracy and sensitivity of parallel factor
      analysis model of dissolved organic matter fluorescence excitation-emission
      matrix.
AB  - Parallel factor (PARAFAC) analysis enables a quantitative analysis of excitation
      emission matrix (EEM). The impact of a spectral variability stemmed from a
      diverse dataset on the representativeness of the PARAFAC model needs to be
      examined. In this study, samples from a river, effluent of a wastewater treatment
      plant, and algae secretion were collected and subjected to PARAFAC analysis.
      PARAFAC models of global dataset and individual datasets were compared. It was
      found that the peak shift derived from source diversity undermined the accuracy
      of the global model. The results imply that building a universal PARAFAC model
      that can be widely available for fitting new EEMs would be quite difficult, but
      fitting EEMs to existing PARAFAC model that belong to a similar environment would
      be more realistic. The accuracy of online monitoring strategy that monitors the
      fluorescence intensities at the peaks of PARAFAC components was examined by
      correlating the EEM data with the maximum fluorescence (Fmax) modeled by PARAFAC.
      For the individual datasets, remarkable correlations were obtained around the
      peak positions. However, an analysis of cocktail datasets implies that the
      involvement of foreign components that are spectrally similar to local components
      would undermine the online monitoring strategy. 

PMID- 25958787
TI  - RGD-decorated conjugated polymer particles as fluorescent biomedical probes
      prepared by Sonogashira dispersion polymerization.
AB  - Here, we present a facile one-step Sonogashira dispersion polymerization
      affording monodisperse conjugated polymer particles bearing accessible acetylene
      moieties on the surface. These acetylene groups are easily functionalized with
      biological recognition motifs using thiol-yne click chemistry. The resulting
      functional particles are applied as fluorescent probes for imaging of activated
      endothelial cells, which take up the particles via receptor mediated endocytosis.

PMID- 25958788
TI  - On the relationship between the basicity of a surface and its ability to catalyze
      transesterification in liquid and gas phases: the case of MgO.
AB  - Gas or liquid phase transesterification reactions are used in the field of
      biomass valorization to transform some platform molecules into valuable products.
      Basic heterogeneous catalysts are often claimed for these applications but the
      role of basicity in the reaction mechanism depending on the operating conditions
      is still under debate. In order to compare the catalyst properties necessary to
      perform a transesterification reaction both in liquid and gas phases, ethyl
      acetate and methanol, which can be easily processed both in these two phases,
      were chosen as reactants. The catalyst studied is MgO, known for its basic
      properties and its ability to perform the reaction. By means of appropriate
      thermal treatments, different kinds of MgO surfaces, with different coverages of
      natural adsorbates (carbonates and hydroxyls groups), can be prepared and
      characterized by means of CO2 adsorption followed by IR spectroscopy and hept-1
      ene isomerization model reaction. New results on the basicity of the natural MgO
      surface (covered by carbonate and hydroxyl groups) are first given and discussed.
      The catalytic behavior in the transesterification reaction is then determined as
      a function of the adsorbate coverage. It is shown that the transesterification
      activity in the liquid phase is directly correlated with the kinetic basicity of
      the surface in agreement with the mechanism already proposed in the literature.
      On the reverse, no direct correlation with the basicity of the surface was
      established with the transesterification activity in the gas phase. A very high
      activity, in the gas phase, was observed and discussed for the natural surface
      pre-treated at 623 K. Preliminary DFT modeling of ester adsorption and methanol
      adsorption capacity determination were performed to investigate plausible
      reaction routes. 

PMID- 25958789
TI  - Linking EEG signals, brain functions and mental operations: Advantages of the
      Laplacian transformation.
AB  - Electroencephalography (EEG) is a very popular technique for investigating brain
      functions and/or mental processes. To this aim, EEG activities must be
      interpreted in terms of brain and/or mental processes. EEG signals being a direct
      manifestation of neuronal activity it is often assumed that such interpretations
      are quite obvious or, at least, straightforward. However, they often rely on
      (explicit or even implicit) assumptions regarding the structures supposed to
      generate the EEG activities of interest. For these assumptions to be used
      appropriately, reliable links between EEG activities and the underlying brain
      structures must be established. Because of volume conduction effects and the
      mixture of activities they induce, these links are difficult to establish with
      scalp potential recordings. We present different examples showing how the
      Laplacian transformation, acting as an efficient source separation method,
      allowed to establish more reliable links between EEG activities and brain
      generators and, ultimately, with mental operations. The nature of those links
      depends on the depth of inferences that can vary from weak to strong. Along this
      continuum, we show that 1) while the effects of experimental manipulation can
      appear widely distributed with scalp potentials, Laplacian transformation allows
      to reveal several generators contributing (in different manners) to these
      modulations, 2) amplitude variations within the same set of generators can
      generate spurious differences in scalp potential topographies, often interpreted
      as reflecting different source configurations. In such a case, Laplacian
      transformation provides much more similar topographies, evidencing the same
      generator(s) set, and 3) using the LRP as an index of response activation most
      often produces ambiguous results, Laplacian-transformed response-locked ERPs
      obtained over motor areas allow resolving these ambiguities. 

PMID- 25958790
TI  - Intelligence measures and stage 2 sleep in typically-developing and autistic
      children.
AB  - The relationship between intelligence measures and 2 EEG measures of non-rapid
      eye movement sleep, sleep spindles and Sigma activity, was examined in 13
      typically-developing (TD) and 13 autistic children with normal IQ and no
      complaints of poor sleep. Sleep spindles and Sigma EEG activity were computed for
      frontal (Fp1, Fp2) and central (C3, C4) recording sites. Time in stage 2 sleep
      and IQ was similar in both groups. Autistic children presented less spindles at
      Fp2 compared to the TD children. TD children showed negative correlation between
      verbal IQ and sleep spindle density at Fp2. In the autistic group, verbal and
      full-scale IQ scores correlated negatively with C3 sleep spindle density. The
      duration of sleep spindles at Fp1 was shorter in the autistic group than in the
      TD children. The duration of sleep spindles at C4 was positively correlated with
      verbal IQ only in the TD group. Fast Sigma EEG activity (13.25-15.75 Hz) was
      lower at C3 and C4 in autistic children compared to the TD children, particularly
      in the latter part of the night. Only the TD group showed positive correlation
      between performance IQ and latter part of the night fast Sigma activity at C4.
      These results are consistent with a relationship between EEG activity during
      sleep and cognitive processing in children. The difference between TD and
      autistic children could derive from dissimilar cortical organization and
      information processing in these 2 groups.

PMID- 25958792
TI  - Factors influencing speech and language outcomes of children with early
      identified severe/profound hearing loss: Clinician-identified facilitators and
      barriers.
AB  - PURPOSE: Early identification of severe/profound childhood hearing loss (HL)
      gives these children access to hearing devices and early intervention to
      facilitate improved speech and language outcomes. Predicting which infants will
      go on to achieve such outcomes remains difficult. This study describes clinician
      identified malleable and non-malleable factors that may influence speech and
      language outcomes for children with severe/profound HL. METHOD: Semi-structured
      interviews were conducted with six experienced auditory verbal clinicians. A
      collective case study design was implemented. The interviews were transcribed and
      coded into themes using constant comparative analysis. RESULT: Clinicians
      identified that, for children with severe/profound HL, early identification,
      early amplification and commencing auditory-verbal intervention under 6 months of
      age may facilitate child progress. Possible barriers were living in rural/remote
      areas, the clinicians' lack of experience and confidence in providing
      intervention for infants under age 6-months and belonging to a family with a
      culturally and linguistically diverse (CALD) background. CONCLUSION: The results
      indicate that multiple factors need to be considered by clinicians working with
      children with HL and their families to determine how each child functions within
      their own environment and personal contexts, consistent with the International
      Classification of Functioning, Disability and Health (ICF) framework. Such an
      approach is likely to empower clinicians to carefully balance potential barriers
      to, and facilitators of, optimal speech and language outcomes for all children
      with HL.

PMID- 25958791
TI  - Diphtheria-toxin based anti-human CCR4 immunotoxin for targeting human CCR4(+)
      cells in vivo.
AB  - CC chemokine receptor 4 (CCR4) has attracted much attention as a promising
      therapeutic drug target for CCR4(+) tumor cells and Tregs. CCR4 is expressed on
      some tumor cells such as T-cell acute lymphoblastic leukemia (ALL), adult T-cell
      leukemia/lymphoma (ATLL), adult peripheral T cell lymphoma (PTCL) and cutaneous T
      cell lymphoma (CTCL). CCR4 is also expressed on majority of Tregs, mainly
      effector Tregs. In this study we have successfully developed three versions of
      diphtheria-toxin based anti-human CCR4 immunotoxins (monovalent, bivalent and
      single-chain fold-back diabody). Binding analysis by flow cytometry showed that
      all three versions of the anti-human CCR4 immunotoxins bound to the human CCR4(+)
      tumor cell line as well as CCR4(+) human PBMC. The bivalent isoform bound
      stronger than its monovalent counterpart and the single-chain foldback diabody
      isoform was the strongest among the three versions. In vitro efficacy analysis
      demonstrated that the bivalent isoform was 20 fold more potent in inhibiting
      cellular proliferation and protein synthesis in human CCR4(+) tumor cells
      compared to the monovalent anti-human CCR4 immunotoxin. The single-chain fold
      back diabody isoform was 10 fold more potent than its bivalent counterpart and
      200 fold more potent than its monovalent counterpart. The in vivo efficacy was
      assessed using a human CCR4(+) tumor-bearing mouse model. The immunotoxin
      significantly prolonged the survival of tumor-bearing NOD/SCID IL-2 receptor
      gamma(-/-) (NSG) mice injected with human CCR4(+) acute lymphoblastic leukemia
      cells compared with the control group. This novel anti-human CCR4 immunotoxin is
      a promising drug candidate for targeting human CCR4(+) tumor cells and Tregs in
      vivo. 

PMID- 25958793
TI  - Atomistic mechanisms of nonstoichiometry-induced twin boundary structural
      transformation in titanium dioxide.
AB  - Grain boundary (GB) phase transformations often occur in polycrystalline
      materials while exposed to external stimuli and are universally implicated in
      substantially affecting their properties, yet atomic-scale knowledge on the
      transformation process is far from developed. In particular, whether GBs loaded
      with defects due to treatments can still be conventionally considered as
      disordered areas with kinetically trapped structure or turn ordered is debated.
      Here we combine advanced electron microscopy, spectroscopy and first-principles
      calculations to probe individual TiO2 GB subject to different atmosphere, and to
      demonstrate that stimulated structural defects can self-assemble at GB, forming
      an ordered structure, which results in GB nonstoichiometry and structural
      transformations at the atomic scale. Such structural transformation is
      accompanied with electronic transition at GB. The three-dimensional
      transformations afford new perspectives on the structural defects at GBs and on
      the development of strategies to manipulate practically significant GB
      transformations. 

PMID- 25958794
TI  - Offsetting or Enhancing Behavior: An Empirical Analysis of Motorcycle Helmet
      Safety Legislation.
AB  - This study uses state-level panel data from a 33-year period to test the
      hypotheses of offsetting and enhancing behavior with regards to motorcycle helmet
      legislation. Results presented in this article find no evidence of offsetting
      behavior and are consistent with the presence of enhancing behavior. State
      motorcycle helmet laws are estimated to reduce motorcycle crashes by 18.4% to
      31.9%. In the absence of any behavioral adaptations among motorcyclists mandatory
      helmet laws are not expected to have any significant impact on motorcycle crash
      rates. The estimated motorcycle crash reductions do not appear to be driven by
      omitted variable bias or nonclassical measurement error in reported crashes.
      Overall, the results strongly suggest that mandatory helmet laws yield
      significant changes in motorcycle mobility in the form of reduced risk taking
      and/or decreased utilization. 

PMID- 25958795
TI  - Iridium Oxide Coatings with Templated Porosity as Highly Active Oxygen Evolution
      Catalysts: Structure-Activity Relationships.
AB  - Iridium oxide is the catalytic material with the highest stability in the oxygen
      evolution reaction (OER) performed under acidic conditions. However, its high
      cost and limited availability demand that IrO2 is utilized as efficiently as
      possible. We report the synthesis and OER performance of highly active mesoporous
      IrO2 catalysts with optimized surface area, intrinsic activity, and pore
      accessibility. Catalytic layers with controlled pore size were obtained by soft
      templating with micelles formed from amphiphilic block copolymers poly(ethylene
      oxide)-b-poly(butadiene)-b-poly(ethylene oxide). A systematic study on the
      influence of the calcination temperature and film thickness on the morphology,
      phase composition, accessible surface area, and OER activity reveals that the
      catalytic performance is controlled by at least two independent factors, that is,
      accessible surface area and intrinsic activity per accessible site. Catalysts
      with lower crystallinity show higher intrinsic activity. The catalyst surface
      area increases linearly with film thickness. As a result of the templated
      mesopores, the pore surface remains fully active and accessible even for thick
      IrO2 films. Even the most active multilayer catalyst does not show signs of
      transport limitations at current densities as high as 75 mA cm(-2) . 

PMID- 25958796
TI  - Family accommodation mediates the association between anxiety symptoms in mothers
      and children.
AB  - OBJECTIVE: The link between child anxiety and maternal anxiety has been well
      established but the factors underlying this association are not well understood.
      One potential factor is family accommodation, which describes ways in which
      parents change their behaviour to help a child avoid or alleviate anxiety. Family
      accommodation has been associated with greater symptom severity, more impairment
      and poorer treatment outcomes in the child. The aim of this study was to
      investigate whether maternal accommodation mediates the relation between parent
      and child anxiety. METHOD: Mothers of children (N = 85) aged 7-17 years (M =
      11.79) completed measures of their own anxiety (State-Trait Anxiety Inventory
      (STAI)), their child's anxiety (Screen for Child Anxiety Related Disorders
      (SCARED)), and family accommodation (Family Accommodation Scale Anxiety (FASA)).
      Structural equation modelling (SEM) was used to test the mediational role of
      accommodation linking parent and child anxiety. RESULTS: Family accommodation was
      found to significantly mediate the link between maternal anxiety and child
      anxiety. CONCLUSION: These results inform theory and imply that the development
      of interventions designed to target family accommodation may improve the
      prognosis of those diagnosed with paediatric anxiety disorders and youth with
      subclinical anxiety symptoms by reducing both parent and child anxiety.

PMID- 25958797
TI  - Factor structure and psychometric properties of the General Health Questionnaire
      (GHQ-12) among Ghanaian adolescents.
AB  - PURPOSE: There is little information about the reliability and validity of the 12
      item General Health Questionnaire (GHQ-12) in Ghana. This study sought to examine
      the reliability and factor structure of the GHQ-12 in Ghanaian adolescents.
      METHODS: High school students (N = 770) completed the GHQ-12 and the Adolescent
      Stress Questionnaire (ASQ). Internal consistency, convergent validity and
      exploratory factor analysis were used. RESULTS: A two factor structure, each with
      six items, was extracted. The total GHQ-12 had acceptable internal consistency
      and a generally high correlation with the ASQ subscales. CONCLUSION: The GHQ-12
      can be used in Ghanaian samples, but more research is needed to confirm its
      factor structure.

PMID- 25958798
TI  - Perceptions of mental healthcare professionals regarding inpatient therapy
      programmes for adolescents in the Eastern Cape, South Africa.
AB  - OBJECTIVES: The study aimed to explore and describe the perceptions of mental
      health professionals with experience working in psychiatric hospitals regarding
      inpatient therapy programmes for adolescents. METHODS: The study followed a
      qualitative, exploratory, descriptive and contextual design. The research
      population included various mental healthcare professionals with experience
      working at psychiatric hospitals in the Eastern Cape. Purposive sampling was
      utilised and semi-structured interviews were conducted. Tesch's eight steps of
      data analysis were followed and Lincoln and Guba's model of trustworthiness was
      utilised. RESULTS: Two main themes emerged from the research. The first
      considered the unique skills and contributions of mental healthcare professionals
      to an adolescent programme. The second theme acknowledged the need for adolescent
      therapy programmes to be holistically structured in order to be effective.
      CONCLUSIONS: The findings showed that inter-professional collaboration is an
      important aspect of successful inpatient adolescent therapy programmes. Such
      programmes benefit from the involvement of a wide variety of professionals.
      However, professionals who are part of a multi-professional team need to be
      suitably skilled and prepared to meet the needs of the adolescent. Professionals
      working in therapy programmes for adolescents should have certain personal
      attributes that make them suitable for working with adolescents. An adolescent
      inpatient therapy programme requires a team leader or a coordinator to lead the
      programme to ensure its success. Continuous assessment of each adolescent is
      essential. Therapy should take place in an adolescent-friendly environment and
      should be structured yet flexible. The involvement of the adolescents' families
      is critical, and the programme should be designed with the family in mind. Group
      therapy is a major component of an adolescent therapy programme and individual
      therapy is also an important aspect of the programme. Finally, adolescents should
      only take part in the programme for a short time to avoid institutionalisation.

PMID- 25958799
TI  - Poetry and narrative therapy for anxiety about spinal surgery.
AB  - This case study presents the use of poetry in psychotherapy with an adolescent
      girl, Buhle (a pseudonym), who needed surgery to correct a curvature of her spine
      due to adolescent idiopathic scoliosis. She experienced anxiety which prevented
      surgeons from doing the procedure. Psychotherapists used narrative therapy to
      explore issues associated with and contributing to her anxiety and encouraged her
      to document her experiences through poetry, after learning that she was a keen
      poet. During psychotherapy Buhle's poems were used to track and narrate her
      experiences and as an empowering method allowing her to make personal sense of
      challenging experiences. Buhle's poems are presented within an account of the
      psychotherapy leading up to the surgery. Her poetry reveals a juxtaposition of
      regular adolescent identity issues in the face of coping with a demanding medical
      condition and the prospect of invasive surgery. 

PMID- 25958802
TI  - Prevalence and distribution of three protozoan symbionts in blue crab
      (Callinectes sapidus) populations across Louisiana, USA.
AB  - Louisiana has one of the largest blue crab (Callinectes sapidus) fisheries in the
      USA, but little is known about blue crab diseases, parasites, and symbionts in
      this area. In 2013-2014, large juvenile and adult blue crabs were collected at 4
      diverse sites to determine the prevalence of the protozoan symbionts associated
      with black gill disease (Lagenophrys callinectes), buckshot crabs (Urosporidium
      crescens), and bitter crab disease (Hematodinium perezi). A high aggregate
      prevalence of L. callinectes (93.2%) was identified across all seasons at all 4
      collection sites regardless of salinity. A moderately low aggregate prevalence of
      U. crescens (22.4%) was identified across all seasons and sites. Prevalence of U.
      crescens depended on site salinity, with only 10% of infections detected at sites
      with <6.3 ppt salinity, and no infections detected at the low salinity site.
      While L. callinectes and U. crescens are commensal parasites of blue crabs,
      infections can result in unmarketable and unappealing meat. In the Louisiana
      fishery, H. perezi has been blamed circumstantially for adult mortalities in the
      low salinity nearshore fishing grounds. Despite this, H. perezi was not detected
      in any of the large crabs sampled, even from the low salinity sites. The
      prevalence data reported here for these 3 protozoans are the first to include
      blue crabs sampled seasonally at multiple locations along the Louisiana coast
      over the period of a year. 

PMID- 25958803
TI  - Genotyping WSSV isolates from northwestern Mexican shrimp farms affected by white
      spot disease outbreaks in 2010-2012.
AB  - White spot disease (WSD) causes high mortality in cultured shrimp throughout the
      world. Its etiologic agent is the white spot syndrome virus (WSSV). The genomic
      repeat regions ORF 75, ORF 94, and ORF 125 have been used to classify WSSV
      isolates in epidemiological studies using PCR with specific primers and
      sequencing. The present study investigated the variation in nucleotide sequences
      from 107, 150, and 143 isolates of WSSV collected from Litopenaeus vannamei
      shrimp ponds with WSD outbreaks in northwestern Mexico during the period 2010
      2012, in the genomic repeat regions ORFs 75, 94, and 125, respectively. The
      haplotypic nomenclature for each isolate was based on the number of repeat units
      and the position of single nucleotide polymorphisms on each ORF. We report
      finding 17, 43, and 66 haplotypes of ORFs 75, 94, and 125, respectively. The
      study found high haplotypic diversity in WSSV using the complete sequences of
      ORFs 94 and 125 as independent variables, but low haplotypic diversity for ORF
      75. Different haplotypes of WSSV were found from region-to-region and year-to
      year, though some individual haplotypes were found in different places and in
      more than one growing cycle. While these results suggest a high rate of mutation
      of the viral genome at these loci, or perhaps the introduction of new viral
      strains into the area, they are useful as a tool for epidemiological surveys. Two
      haplotypes from some of the ORFs in the same shrimp were encountered, suggesting
      the possibility of multiple infections. 

PMID- 25958804
TI  - Testing of candidate non-lethal sampling methods for detection of Renibacterium
      salmoninarum in juvenile Chinook salmon Oncorhynchus tshawytscha.
AB  - Non-lethal pathogen testing can be a useful tool for fish disease research and
      management. Our research objectives were to determine if (1) fin clips, gill
      snips, surface mucus scrapings, blood draws, or kidney biopsies could be obtained
      non-lethally from 3 to 15 g Chinook salmon Oncorhynchus tshawytscha, (2) non
      lethal samples could accurately discriminate between fish exposed to the
      bacterial kidney disease agent Renibacterium salmoninarum and non-exposed fish,
      and (3) non-lethal samples could serve as proxies for lethal kidney samples to
      assess infection intensity. Blood draws and kidney biopsies caused >=5% post
      sampling mortality (Objective 1) and may be appropriate only for larger fish, but
      the other sample types were non-lethal. Sampling was performed over 21 wk
      following R. salmoninarum immersion challenge of fish from 2 stocks (Objectives 2
      and 3), and nested PCR (nPCR) and real-time quantitative PCR (qPCR) results from
      candidate non-lethal samples were compared with kidney tissue analysis by nPCR,
      qPCR, bacteriological culture, enzyme-linked immunosorbent assay (ELISA),
      fluorescent antibody test (FAT) and histopathology/immunohistochemistry. R.
      salmoninarum was detected by PCR in >50% of fin, gill, and mucus samples from
      challenged fish. Mucus qPCR was the only non-lethal assay exhibiting both
      diagnostic sensitivity and specificity estimates>90% for distinguishing between
      R. salmoninarum-exposed and non-exposed fish and was the best candidate for use
      as an alternative to lethal kidney sample testing. Mucus qPCR R. salmoninarum
      quantity estimates reflected changes in kidney bacterial load estimates, as
      evidenced by significant positive correlations with kidney R. salmoninarum
      infection intensity scores at all sample times and in both fish stocks, and were
      not significantly impacted by environmental R. salmoninarum concentrations.

PMID- 25958805
TI  - Morbidity and mortality in stranded Cook Inlet beluga whales Delphinapterus
      leucas.
AB  - The endangered Cook Inlet (Alaska, USA) stock of beluga whales Delphinapterus
      leucas declined 47% between 1994 and 1998, from an estimated 653 whales to 347
      whales, with a continued decline to approximately 312 in 2012. Between 1998 and
      2013, 164 known dead strandings were reported by the National Marine Fisheries
      Service. Only 38 of these animals, or 23% of the known stranded carcasses, were
      necropsied. Carcasses were found between April and October. The majority of
      animals necropsied were adults (n=25), followed by juveniles (n=6), calves (n=3),
      and aborted fetuses (n=4). Eight of the 11 mature females were pregnant, post
      partum, or lactating. Many (82%) of these belugas were in moderate to advanced
      autolysis, which hampered determination of a cause of death (COD). Each animal
      had a single primary COD assigned within a broad set of categories. The CODs were
      unknown (29%), trauma (18%), perinatal mortality (13%), mass stranding (13%),
      single stranding (11%), malnutrition (8%), or disease (8%). Other disease
      processes were coded as contributory or incidental to COD. Multiple animals had
      mild to moderate verminous pneumonia due to Stenurus arctomarinus, renal
      granulomas due to Crassicauda giliakiana, and ulcerative gastritis due to
      Anisakis sp. Each stranding affords a unique opportunity to obtain natural
      history data and evidence of human interactions, and, by long-term monitoring, to
      characterize pathologies of importance to individual and population health.

PMID- 25958806
TI  - Chytrid fungus acts as a generalist pathogen infecting species-rich amphibian
      families in Brazilian rainforests.
AB  - The fungus Batrachochytrium dendrobatidis (Bd) is among the main causes of
      declines in amphibian populations. This fungus is considered a generalist
      pathogen because it infects several species and spreads rapidly in the wild. To
      date, Bd has been detected in more than 100 anuran species in Brazil, mostly in
      the southern portion of the Atlantic forest. Here, we report survey data from
      some poorly explored regions; these data considerably extend current information
      on the distribution of Bd in the northern Atlantic forest region. In addition, we
      tested the hypothesis that Bd is a generalist pathogen in this biome. We also
      report the first positive record for Bd in an anuran caught in the wild in
      Amazonia. In total, we screened 90 individuals (from 27 species), of which 39
      individuals (from 22 species) were Bd-positive. All samples collected in Bahia (2
      individuals), Pernambuco (3 individuals), Para (1 individual), and Minas Gerais
      (1 individual) showed positive results for Bd. We found a positive correlation
      between anuran richness per family and the number of infected species in the
      Atlantic forest, supporting previous observations that Bd lacks strong host
      specificity; of 38% of the anuran species in the Atlantic forest that were tested
      for Bd infection, 25% showed positive results. The results of our study exemplify
      the pandemic and widespread nature of Bd infection in amphibians. 

PMID- 25958807
TI  - Chytridiomycosis in dwarf African frogs Hymenochirus curtipes.
AB  - Chytridiomycosis, resulting from an infection with the fungal agent
      Batrachochytrium dendrobatidis (Bd), has resulted in widespread population
      declines in both wild and captive amphibians. The dwarf African frog (DAF)
      Hymenochirus curtipes is native to central Africa and is commonly sold throughout
      North America as an aquarium pet species. Here we document fatal chytridiomycosis
      resulting from cutaneous Bd infections in DAF purchased directly from a pet store
      and from a historical lethal epizootic occurring at an aquaculture facility in
      central California, USA, more than 25 yr ago. Histological lesions and PCR
      amplified sequence data were consistent with the etiology of Bd. The potential
      epidemiological relevance of this infection in DAF is discussed. 

PMID- 25958808
TI  - First case of ranavirus and associated morbidity and mortality in an eastern mud
      turtle Kinosternon subrubrum in South Carolina.
AB  - Ranaviruses are double-stranded DNA viruses that infect amphibians, fish, and
      reptiles, causing global epidemics in some amphibian populations. It is important
      to identify new species that may be susceptible to the disease, particularly if
      they reside in the same habitat as other at-risk species. On the Savannah River
      Site (SRS) in Aiken, South Carolina, USA, ranaviruses are present in several
      amphibian populations, but information is lacking on the presence, prevalence,
      and morbidity of the virus in reptile species. An eastern mud turtle Kinosternon
      subrubrum captured on the SRS in April 2014 exhibited clinical signs of a
      ranaviral infection, including oral plaque and conjunctivitis. Quantitative PCR
      analyses of DNA from liver tissue, ocular, oral, nasal, and cloacal swabs were
      all positive for ranavirus, and sequencing of the template confirmed infection
      with a FV3-like ranavirus. Histopathologic examination of postmortem tissue
      samples revealed ulceration of the oral and tracheal mucosa, intracytoplasmic
      epithelial inclusions in the oral mucosa and tongue sections, individualized and
      clusters of melanomacrophages in the liver, and bacterial rods located in the
      liver, kidney, heart, stomach, and small intestine. This is the first report of
      morbidity and mortality of a mud turtle with a systemic ranaviral infection. 

PMID- 25958809
TI  - Coxiella burnetii exposure in northern sea otters Enhydra lutris kenyoni.
AB  - Valvular endocarditis has been well described in northern sea otters Enhydra
      lutris kenyoni of Alaska and in many cases no cause has been identified. It is
      also one of the most common conditions observed in people with chronic Coxiella
      burnetii infection. Given the high levels of C. burnetii exposure in marine
      mammals distributed throughout the same geographic range as the northern sea
      otter, and the presence of valvular lesions seen in otters, the objective of this
      study was to determine the level of C. burnetii exposure in otters and
      investigate any association between exposure, infection and valvular disease in
      this species. Archived serum from 75 live captured, apparently healthy otters (25
      from each of 3 stocks) and 30 dead otters were tested for C. burnetii antibodies
      by indirect florescent antibody assay (IFA). Archived bone marrow and heart
      valves were tested for C. burnetii DNA by real-time PCR (qPCR). Overall, the
      seroprevalence in live otters was 17%, with significantly more exposed animals in
      the south central (40%) stock relative to the southwest (8%) and southeast (4%).
      The seroprevalence of animals sampled post mortem was 27%, although none of the
      bone marrow or heart valve samples were positive by qPCR. Results of this study
      failed to demonstrate a significant association between C. burnetii infection and
      valvular endocarditis in sea otters; however, the differing seroprevalence
      suggests that exposure opportunities vary geographically. 

PMID- 25958810
TI  - Commentary on 'Early and Long-term Outcome after Open Surgical Suprarenal Aortic
      Fenestration in Patients with Complicated Acute Type B Aortic Dissection'.

PMID- 25958811
TI  - The role of pathogen shedding in linking within- and between-host pathogen
      dynamics.
AB  - A model linking within- and between-host pathogen dynamics via pathogen shedding
      (emission of pathogens throughout the course of infection) is developed, and
      several aspects of host availability and co-infection are considered. In this
      model, the rate of pathogen shedding affects both the pathogen population size
      within a host (also affecting host mortality) and the rate of infection of new
      hosts. Our goal is to ascertain how the rate of shedding is likely to evolve, and
      what factors permit coexistence of alternative shedding rates in a pathogen
      population. For a constant host population size (where an increase in infected
      hosts necessarily decreases susceptible hosts), important differences arise
      depending on whether pathogens compete only for susceptible (uninfected) hosts,
      or whether co-infection allows for competition for infected hosts. With no co
      infection, the pathogen type that can persist with the lowest number of
      susceptible hosts will outcompete any other, which under the assumptions of the
      model is the pathogen with the highest basic reproduction number. This is often a
      pathogen with a relatively high shedding rate (s). If within-host competition is
      allowed, a trade-off develops due to the conflicting effects of shedding on
      within- and between-host pathogen dynamics, with within-host competition favoring
      clones with low shedding rates while between-host competition benefits clones
      with higher shedding rates. With within-host competition for the same host cells,
      low shedding rate clones should eliminate high-s clones in a co-infected host, if
      equilibrium is reached. With co-infection, but no within-host competition,
      pathogen clones still interact by affecting the mortality of co-infected hosts;
      here, coexistence is more likely. With co-infection, two clones can coexist if
      one is the superior competitor for uninfected hosts and the other for co-infected
      hosts. 

PMID- 25958812
TI  - DA 5505: a novel topical formulation of terbinafine that enhances skin
      penetration and retention.
AB  - Topical fungal infections can become severe if left untreated. Efficient
      treatment modalities for topical fungal infections aid the penetration of
      antifungal agents deep into viable skin layers. Terbinafine is a fungicidal agent
      that inhibits ergosterol, an essential fungal component. The main objective of
      this study was to evaluate skin permeation and retention of a terbinafine-loaded
      solution containing chitosan as a film former. Comparative assessment of skin
      permeation and retention was performed using a prepared formulation (DA 5505) and
      marketed formulations of terbinafine in murine and porcine skin. To mimic fungal
      infection of skin, keratinized skin was induced in NC/Nga mice. In comparison
      with the marketed formulations, DA 5505 exhibited significantly better skin
      permeation. The flux, permeation coefficient, and enhancement ratio of
      terbinafine were remarkably increased by DA 5505 in comparison with the marketed
      formulations, and lag time was dramatically reduced. DA 5505 significantly
      increased cumulative terbinafine retention in viable skin layers in comparison
      with the marketed solution, suggesting enhanced efficacy. Furthermore, DA 5505
      exhibited superior skin permeation in normal skin and keratinized skin. Thus, the
      DA 5505 formulation has the potential to effectively deliver terbinafine to
      superficial and deep cutaneous fungal infections. 

PMID- 25958813
TI  - Pancreatic and Extrapancreatic Features in Autoimmune Pancreatitis.
AB  - Autoimmune pancreatitis (AIP) accounts for approximately 5% of chronic
      pancreatitis cases and is an important consideration in the differential
      diagnosis of pancreatic pathologies. The underlying pathophysiology of AIP is
      thought to involve lymphocyte infiltration and associated sclerosis. Although AIP
      is a benign condition that is treatable with corticosteroids, it can have imaging
      and clinical findings indistinguishable from pancreatic cancer. As such, the
      radiologist plays an important management role in distinguishing AIP from more
      sinister conditions. In addition, there are several extrapancreatic imaging
      findings in the context of AIP that have been recently described. This pictorial
      review outlines both the pancreatic and extrapancreatic imaging features in AIP
      and the response to steroid therapy. Important imaging features that allow AIP to
      be differentiated from other pancreatic pathology, including adenocarcinoma,
      lymphoma, and acute pancreatitis will be discussed. 

PMID- 25958814
TI  - Simultaneous detection of IgG and IgM antibodies against a recombinant
      polyprotein PstS1-LEP for tuberculosis diagnosis.
AB  - BACKGROUND: Commercial serological tests for the diagnosis of tuberculosis (TB)
      show poor sensitivity and specificity, and a new approach to antigen screening is
      required to improve the accuracy of serodiagnosis. METHODS: Using an indirect
      enzyme-linked immunosorbent assay (ELISA), we evaluated the responses of IgG and
      IgM antibodies to the recombinant PstS1-LEP protein expressed in Escherichia
      coli, a polyprotein of PstS1 and line multi-epitopes polypeptide (LEP). RESULTS:
      The mixture of anti-human IgG and IgM added to a well [Ig(G + M)], which was
      different from the combination of IgG and IgM (IgG + IgM), had a stronger
      immunoreactivity to PstS1-LEP than the single antibody. IgG and Ig(G + M), but
      not IgM against the PstS1-LEP protein effectively distinguished TB patients from
      patients with nontuberculous pulmonary disease (NTBPD) and healthy controls
      (HCs). Compared with IgG, the sensitivities of Ig(G + M) and IgG + IgM varied
      from 71.4% to 77.6% and 72.7% in pulmonary TB (PTB) patients and from 42.1% to
      64.0% and 55.8% in extrapulmonary TB (EPTB) patients, respectively. The
      specificity of Ig(G + M) did not decrease, and was higher than that provided by
      IgG + IgM in HCs with positive tuberculin skin test. CONCLUSION: These findings
      suggest that PstS1-LEP can act as a candidate for detecting Ig(G + M) in serum
      from PTB and EPTB patients.

PMID- 25958815
TI  - Heat-shock protein 90 (Hsp90) as anticancer target for drug discovery: an ample
      computational perspective.
AB  - There are over 100 different types of cancer, and each is classified based on the
      type of cell that is initially affected. If left untreated, cancer can result in
      serious health problems and eventually death. Recently, the paradigm of cancer
      chemotherapy has evolved to use a combination approach, which involves the use of
      multiple drugs each of which targets an individual protein. Inhibition of heat
      shock protein 90 (Hsp90) is one of the novel key cancer targets. Because of its
      ability to target several signaling pathways, Hsp90 inhibition emerged as a
      useful strategy to treat a wide variety of cancers. Molecular modeling approaches
      and methodologies have become 'close counterparts' to experiments in drug design
      and discovery workflows. A wide range of molecular modeling approaches have been
      developed, each of which has different objectives and outcomes. In this review,
      we provide an up-to-date systematic overview on the different computational
      models implemented toward the design of Hsp90 inhibitors as anticancer agents.
      Although this is the main emphasis of this review, different topics such as
      background and current statistics of cancer, different anticancer targets
      including Hsp90, and the structure and function of Hsp90 from an experimental
      perspective, for example, X-ray and NMR, are also addressed in this report. To
      the best of our knowledge, this review is the first account, which
      comprehensively outlines various molecular modeling efforts directed toward
      identification of anticancer drugs targeting Hsp90. We believe that the
      information, methods, and perspectives highlighted in this report would assist
      researchers in the discovery of potential anticancer agents. 

PMID- 25958816
TI  - Ethnical Differences in Breast Cancer Characteristics in South African
      Population.

PMID- 25958817
TI  - Expectant management for men with early stage prostate cancer.
AB  - Since the dissemination of prostate-specific antigen screening, most men with
      prostate cancer are now diagnosed with localized, low-risk prostate cancer that
      is unlikely to be lethal. Nevertheless, nearly all of these men undergo primary
      treatment with surgery or radiation, placing them at risk for longstanding side
      effects, including erectile dysfunction and impaired urinary function. Active
      surveillance and other observational strategies (ie, expectant management) have
      produced excellent long-term disease-specific survival and minimal morbidity for
      men with prostate cancer. Despite this, expectant management remains underused
      for men with localized prostate cancer. In this review, various approaches to the
      expectant management of men with prostate cancer are summarized, including
      watchful waiting and active surveillance strategies. Contemporary cancer-specific
      and health care quality-of-life outcomes are described for each of these
      approaches. Finally, contemporary patterns of use, potential disparities in care,
      and ongoing research and controversies surrounding expectant management of men
      with localized prostate cancer are discussed.

PMID- 25958819
TI  - Psychological factors and mental health in persons with spinal cord injury: An
      exploration of change or stability.
AB  - OBJECTIVES: To examine the course of mental health and psychological factors over
      time in persons with a recent spinal cord injury and to determine whether change
      in psychological factors is associated with change in mental health. DESIGN:
      Prospective cohort study in the Netherlands with 3 measurement time-points.
      SUBJECTS: A total of 60 persons with recently acquired spinal cord injury.
      METHODS: Standardized validated measurement instruments were used to assess
      mental health, self-efficacy, mastery, optimism, illness cognitions, purpose in
      life, and social comparison. Descriptive statistics and multilevel analysis were
      used. RESULTS: Multilevel regression analyses showed that neither mental health
      nor psychological factors, except for social comparison-upward identification,
      showed statistically significant change over time. However, increasing scores for
      self-efficacy, mastery, acceptance cognitions, and purpose in life were
      significantly associated with increasing mental health. In contrast, increasing
      scores for optimism, social comparison, helplessness cognitions, and disease
      benefits cognitions were not significantly associated with increasing mental
      health in persons with spinal cord injury. CONCLUSION: Most psychological factors
      showed stability up to 6 months post-discharge. Purpose in life, acceptance
      cognitions, self-efficacy, and mastery showed more variability and seem to be
      most promising as targets for interventions, which may lead to an improvement in
      mental health in persons with spinal cord injury.

PMID- 25958818
TI  - Site of eustachian tube obstruction in chronic ear disease.
AB  - OBJECTIVE: Assess the patency of the proximal and distal segments of the
      Eustachian tube in patients undergoing surgery for chronic ear disease. STUDY
      DESIGN: Case study with control group. METHODS: All consecutive patients
      presenting for surgery for chronic ear disease in our practice over 14 months
      underwent preoperative Valsalva computed tomography (CT), and an attempt was made
      intraoperatively using angled rigid scopes to evaluate obstruction of the
      protympanic segment of the Eustachian tube. Endoscopic examination of the same
      segment in 19 cadaver ears served as a control group. RESULTS: Preoperative
      Valsalva CT showed patency of the distal one-third of the Eustachian tube in 51
      of 53 ears. Intraoperative endoscopy allowed visualization of the protympanic
      opening of the Eustachian tube in 31 of 53 ears; 21 of 31 ears showed obstruction
      of the protympanic opening of the Eustachian tube. CONCLUSION: A clear
      obstruction was more likely to be present in the protympanic opening of the
      Eustachian tube in the patient population undergoing surgery for chronic ear
      disease than in the cadaver control group, and was equally likely to be present
      in the distal cartilaginous tube in patients as in the control population. LEVEL
      OF EVIDENCE: 4.

PMID- 25958820
TI  - Neonatal medicines research: challenges and opportunities.
AB  - INTRODUCTION: The key feature of the newborn is its fast age-dependent
      maturation, resulting in extensive variability in pharmacokinetics and -dynamics,
      further aggravated by newly emerging covariates like treatment modalities,
      environmental issues or pharmacogenetics. This makes clinical research in
      neonates relevant and needed, but also challenging. AREAS COVERED: To improve
      this knowledge, tailoring research tools as well as building research networks
      and clinical research skills for neonates are urgently needed. Tailoring of
      research tools is illustrated using the development of dried blood spot
      techniques and the introduction of micro-dosing and -tracer methodology in
      neonatal drug studies. Both techniques can be combined with sparse sampling
      techniques through population modeling. Building research networks and clinical
      research skills is illustrated by the initiatives of agencies to build and
      integrate knowledge on neonatal pharmacotherapy through dedicated working groups.
      EXPERT OPINION: Challenges relating to neonatal medicine research can largely be
      overcome. Tailored tools and legal initiatives, combined with clever trial design
      will result in more robust information on neonatal pharmacotherapy. This
      necessitates collaborative efforts between clinical researchers, sponsors,
      regulatory authorities, and last but not least patient representatives and
      society.

PMID- 25958821
TI  - Effects of 11-ketotestosterone and temperature on inhibin subunit mRNA levels in
      the ovary of the shortfinned eel, Anguilla australis.
AB  - Members of the transforming growth factor-b (TGFb) superfamily are important
      during early oogenesis in mammals. In this study, we tested whether documented
      effects of 11-ketotestosterone (11KT) on previtellogenic eel ovaries are mediated
      through affecting the expression of key ovarian TGFb genes. Furthermore, we
      investigated whether 11KT effects interacted with temperature. Accordingly, three
      thermal regimes were compared and their interaction with 11KT-mediated actions on
      expression of TGFb superfamily genes (chiefly inhibin subunits) evaluated in the
      eel (Anguilla australis). Inhibin subunit mRNA levels were also measured in
      ovarian explants cultured in vitro with 11KT and in ovaries from eels collected
      from the wild. In wild eels, inhibin-bA mRNA levels were higher in early than in
      previtellogenic eels; inhibin-a expression did not differ between stages, whereas
      that of inhibin-bB first decreased, then recovered with advanced developmental
      stage. Temperature was ineffective in modulating any of the end points, at least
      as long as a Q10 adjustment was made to correct for 'metabolic dose'. However,
      11KT affected the expression of inhibin-a compared to control fish, while those
      of inhibin-b subunit genes remained unaffected. In contrast, 11KT dramatically
      reduced mRNA levels of inhibin-b subunits in vitro, but had inconsistent effects
      on inhibin-a transcript abundance. We conclude that 11KT affects ovarian inhibin
      subunit gene expression, but effects are not in keeping with the changes seen
      during early oogenesis in eels from the wild. We further contend that in vivo
      temperature experiments are easily biased and that Q10 corrections may be
      required to identify 'true' temperature effects. 

PMID- 25958822
TI  - Attention bias modification in specific fears: Spiders versus snakes.
AB  - BACKGROUND AND OBJECTIVES: Attention Bias Modification (ABM) is used to
      manipulate attention biases in anxiety disorders. It has been successful in
      reducing attention biases and anxious symptoms in social anxiety and generalized
      anxiety, but not yet in specific fears and phobias. METHODS: We designed a new
      version of the dot-probe training task, aiming to train fearful participants'
      attention away from or towards pictures of threatening stimuli. Moreover, we
      studied whether the training also affected participants' avoidance behavior and
      their physical arousal upon being confronted with a real threat object. RESULTS:
      In Experiment 1, students with fear of spiders were trained. We found that the
      attention manipulation was successful, but the training failed to affect behavior
      or arousal. In Experiment 2, the same procedure was used on snake-fearful
      students. Again, attention was trained in the expected directions. Moreover,
      participants whose attention had been trained away from snakes showed lower
      physiological arousal upon being confronted with a real snake. LIMITATIONS: The
      study involved healthy students with normal distribution of the fear of
      spider/snake. Future research with clinical sample could help with determining
      the generalizability of the current findings. CONCLUSIONS: The effect of ABM on
      specific phobia is still in question. The finding in the present study suggested
      the possibility to alter attentional bias with a dot-probe task with general
      positive stimuli and this training could even affect the behavior while
      encountering a real threat.

PMID- 25958823
TI  - Clinical profiles for seizure remission and developmental gains after total
      corpus callosotomy.
AB  - PURPOSE: This study was aimed to determine what preoperative profiles were
      associated with seizure remission after corpus callosotomy and whether such
      seizure outcome was associated with the postoperative developmental outcome.
      METHODS: This retrospective study included 26 consecutive patients with childhood
      onset epilepsy who underwent one-stage total corpus callosotomy at our
      institution and were followed up for a minimum of 1 year. The age at surgery
      ranged from 13 months to 32 years (median 6 years). The association between
      postoperative seizure freedom and preoperative profiles, post-operative
      developmental gains was examined. RESULTS: Five patients achieved seizure freedom
      (Engel class I), and 10 patients achieved worthwhile reduction of seizures (class
      III), whereas the remaining patients had a class IV outcome. All five seizure
      free patients had "lack of abnormal magnetic resonance imaging findings", "lack
      of proven etiology of seizures", and underwent "surgery at age 6 years or
      younger". These three factors were associated with seizure freedom (p<0.05,
      Fisher exact test). Post-operative gains in developmental quotient were
      significantly better in patients with seizure freedom than in those without
      (p<0.05, Mann Whitney U test). CONCLUSION: Our study replicated the notion that
      seizure remission can be achieved after total corpus callosotomy in subsets of
      patients with medically-uncontrolled epilepsy, and suggested that a better
      developmental outcome can be expected in patients benefiting from seizure
      freedom.

PMID- 25958824
TI  - Solid lithium electrolytes based on an organic molecular porous solid.
AB  - A new type of solid lithium-ion conducting electrolytes prepared by incorporation
      of Li(+) ions into a cucurbit[6]uril (CB[6])-based organic molecular porous solid
      shows high Li(+) ion conductivity (~10(-4) S cm(-1)) and mobility (transference
      numbers, tLi(+) = 0.7-0.8). In addition, the solid electrolytes show excellent,
      thermally stable performance even after several temperature cycles. 

PMID- 25958825
TI  - Copper malonamide complexes and their use in azide-alkyne cycloaddition
      reactions.
AB  - We report a rare example of the malonamide functionality being used as a ligand
      in copper catalysis. We have ligated a homologous series of these O,O-chelating
      architectures to copper, investigated their structure and exploited them in azide
      alkyne cycloaddition reactions for the step-growth synthesis of oligo(triazoles)
      and in the synthesis of small organic azoles. 

PMID- 25958826
TI  - Phloem sap proteome studied by iTRAQ provides integrated insight into salinity
      response mechanisms in cucumber plants.
AB  - Cucumber is an economically important crop as well as a model system for plant
      vascular biology. Salinity is one of the major environmental factors limiting
      plant growth. Here, we used an iTRAQ-based quantitative proteomics approach for
      comparative analysis of protein abundances in cucumber phloem sap in response to
      salt. A total of 745 distinct proteins were identified and 111 proteins were
      differentially expressed upon salinity in sensitive and tolerant cultivars, of
      which 69 and 65 proteins changed significantly in sensitive and tolerant
      cultivars, respectively. A bioinformatics analysis indicated that cucumber phloem
      employed a combination of induced metabolism, protein turnover, common stress
      response, energy and transport, signal transduction and regulation of
      transcription, and development proteins as protection mechanisms against
      salinity. The proteins that were mapped to the carbon fixation pathway decreased
      in abundance in sensitive cultivars and had no change in tolerant cultivars under
      salt stress, suggesting that this pathway may promote salt tolerance by
      stabilizing carbon fixation and maintaining the essential energy and
      carbohydrates in tolerant cultivars. This study leads to a better understanding
      of the salinity mechanism in cucumber phloem and provides a list of potential
      gene targets for the further engineering of salt tolerance in plants. 

PMID- 25958827
TI  - Pollen feeding proteomics: Salivary proteins of the passion flower butterfly,
      Heliconius melpomene.
AB  - While most adult Lepidoptera use flower nectar as their primary food source,
      butterflies in the genus Heliconius have evolved the novel ability to acquire
      amino acids from consuming pollen. Heliconius butterflies collect pollen on their
      proboscis, moisten the pollen with saliva, and use a combination of mechanical
      disruption and chemical degradation to release free amino acids that are
      subsequently re-ingested in the saliva. Little is known about the molecular
      mechanisms of this complex pollen feeding adaptation. Here we report an initial
      shotgun proteomic analysis of saliva from Heliconius melpomene. Results from
      liquid-chromatography tandem mass-spectrometry confidently identified 31 salivary
      proteins, most of which contained predicted signal peptides, consistent with
      extracellular secretion. Further bioinformatic annotation of these salivary
      proteins indicated the presence of four distinct functional classes: proteolysis
      (10 proteins), carbohydrate hydrolysis (5), immunity (6), and "housekeeping" (4).
      Additionally, six proteins could not be functionally annotated beyond containing
      a predicted signal sequence. The presence of several salivary proteases is
      consistent with previous demonstrations that Heliconius saliva has proteolytic
      capacity. It is likely that these proteins play a key role in generating free
      amino acids during pollen digestion. The identification of proteins functioning
      in carbohydrate hydrolysis is consistent with Heliconius butterflies consuming
      nectar, like other lepidopterans, as well as pollen. Immune-related proteins in
      saliva are also expected, given that ingestion of pathogens is a likely route to
      infection. The few "housekeeping" proteins are likely not true salivary proteins
      and reflect a modest level of contamination that occurred during saliva
      collection. Among the unannotated proteins were two sets of paralogs, each
      seemingly the result of a relatively recent tandem duplication. These results
      offer a first glimpse into the molecular foundation of Heliconius pollen feeding
      and provide a substantial advance towards comprehensively understanding this
      striking evolutionary novelty. 

PMID- 25958828
TI  - Providing alternative reinforcers to facilitate tolerance to delayed
      reinforcement following functional communication training.
AB  - The earliest stages of functional communication training (FCT) involve providing
      immediate and continuous reinforcement for a communicative response (FCR) that is
      functionally equivalent to the targeted problem behavior. However, maintaining
      immediate reinforcement is not practical, and the introduction of delays is
      associated with increased problem behavior. The present study evaluated the
      effects of providing alternative reinforcers during delays to reinforcement with
      a 13-year-old boy with an intellectual disability. Problem behavior was less
      likely when alternative reinforcers were available during delays. 

PMID- 25958829
TI  - Quantification of tumor infiltrating Foxp3+ regulatory T cells enables the
      identification of high-risk patients for developing synchronous cancers over
      upper aerodigestive tract.
AB  - OBJECTIVES: Patients with squamous cell carcinomas (SCC) of upper aerodigestive
      tract, either over head and neck (HNSCC) or esophagus (ESCC), frequently
      developed synchronous multiple cancers, leading to worse prognosis. This study
      validated whether suppression of host cancer immunosurveillance mediated by
      regulatory T cells (Treg) may predispose to the development of synchronous
      cancers. METHODS: Tumor tissues of 200 patients (100 ESCC only, 50 HNSCC only,
      and 50 synchronous SCCs) were quantitatively accessed for the tumor infiltrating
      Treg by immunohistochemistry. The density of Treg was also correlated to the
      level of Treg-associated inhibitory cytokines (IL-10, IL-35 and TGF-beta1), and
      chemokine (CCL22). RESULTS: The density of tumor infiltrating Treg in the index
      tumor (i.e. the first malignancy diagnosed) of synchronous SCC group was higher
      than those of HNSCC or ESCC only (p<0.05). Selecting the optimal cut-off value of
      Treg density as 34.6 cells/mm(2) by ROC curve, an increased Treg density of the
      index tumor can be an independent factor for developing synchronous SCCs (OR:
      6.13; 95% CI: 2.84-13.26). The Treg density was positively correlated with serum
      IL-10 level and the degree of CCL22-positive cells infiltration in tumor.
      Furthermore, the serum inhibitory cytokine IL-10 level was higher in synchronous
      SCC than in non-synchronous ones (p<0.001), that indicated the cellular
      immunosuppression in patients with synchronous cancers. CONCLUSIONS: A more
      severe defect in cellular immunity may predispose to multifocal tumor. The Treg
      cell number in SCC may serve as a novel predictive biomarker for the risk of
      synchronous cancer development to initiate a proper surveillance program.

PMID- 25958830
TI  - Definitive chemoradiation for primary oral cavity carcinoma: A single institution
      experience.
AB  - OBJECTIVES: While surgery with or without adjuvant radiation therapy (RT) is the
      standard of care for oral cavity cancer (OCC), a select group requires
      nonsurgical treatment. We provide a single-institution experience using
      definitive chemotherapy and RT for primary OCC. MATERIALS AND METHODS: We
      examined 73 patients with previously untreated, non-metastatic primary OCC
      treated definitively from 1990 to 2011. There were 39 male and 34 female, with a
      median age of 63 years (range, 35-89). The disease distribution was Stage I and
      II (7% each), Stage III (14%), and Stage IV (73%). Oral tongue was the most
      common (48%), followed by floor of mouth (19%), retromolar trigone (13.7%), and
      others (8.2%). Median tumor dose was 70 Gy. Sixty-two percent of patients (n=45)
      were treated with concurrent chemotherapy, predominantly platinum-based. RESULTS:
      Median follow-up among surviving patients was 73.1 months (interquartile range
      14.2-81.4 months). Actuarial 5-year overall survival was 15%. Incidences of
      locoregional and distant failures were 41.1% and 20.5%, respectively. Kaplan
      Meier estimated 5-year rates of locoregional control and freedom from distant
      metastasis were 37% and 70%, respectively. Mucositis was the most common ?Grade 3
      acute toxicity (49%). Incidences of Grade 3 late dysphagia and trismus were 15%
      and 13%, respectively. CONCLUSION: This study demonstrates over 20 years of
      experience using definitive chemoradiation for OCC at our institution. Our
      results illustrate the challenges in treating patients with advanced disease who
      are not surgical candidates, and the need for adequate and early treatment to
      prevent distant disease and improve survival outcomes.

PMID- 25958831
TI  - Carotid sparing intensity-modulated radiation therapy achieves comparable
      locoregional control to conventional radiotherapy in T1-2N0 laryngeal carcinoma.
AB  - BACKGROUND: Although intensity-modulated radiotherapy (IMRT) is a standard of
      care for many head and neck cancers, its use for carotid-sparing (CS) therapy in
      early-stage laryngeal carcinoma is controversial. METHODS: 330 consecutive
      patients with early-stage laryngeal carcinoma were treated from 1/1989 to 5/2011,
      including 282 conventional radiotherapy (CRT) and 48 CS-IMRT patients. The median
      follow-up was 43 (CS-IMRT) and 66 (CRT) months. RESULTS: There was no difference
      in local failure rates comparing patients undergoing CS-IMRT with CRT, with 3
      year local control rates of 88% vs. 89%, respectively (p=0.938). Using a 1cm
      circumferential margin, the average dose to the left and right carotid arteries
      was 48.3 and 47.9 Gy, respectively. 88% of locoregional recurrences involved the
      ipsilateral true vocal cord, including all local recurrences in the IMRT group.
      CONCLUSIONS: These results warrant further prospective evaluation of CS-IMRT for
      early-stage glottic larynx cancer.

PMID- 25958833
TI  - A facile one-pot synthesis of colloidal stable, monodisperse, highly PEGylated
      CuS@mSiO2 nanocomposites for the combination of photothermal therapy and
      chemotherapy.
AB  - A facile one-pot approach was developed for the synthesis of colloidal stable,
      monodisperse, highly PEGylated mesoporous silica coated copper sulfide
      nanocomposites for the combination of photothermal therapy and chemotherapy. The
      proposed method can also be extended to the synthesis of other metal sulfide
      nanocomposites. 

PMID- 25958834
TI  - Plant-based Foods: Seed, Nutrition and Human Health.

PMID- 25958832
TI  - Identification of IL-1beta and LPS as optimal activators of monolayer and
      alginate-encapsulated mesenchymal stromal cell immunomodulation using design of
      experiments and statistical methods.
AB  - Induction of therapeutic mesenchymal stromal cell (MSC) function is dependent
      upon activating factors present in diseased or injured tissue microenvironments.
      These functions include modulation of macrophage phenotype via secreted molecules
      including prostaglandin E2 (PGE2). Many approaches aim to optimize MSC-based
      therapies, including preconditioning using soluble factors and cell
      immobilization in biomaterials. However, optimization of MSC function is usually
      inefficient as only a few factors are manipulated in parallel. We utilized
      fractional factorial design of experiments to screen a panel of 6 molecules
      (lipopolysaccharide [LPS], polyinosinic-polycytidylic acid [poly(I:C)],
      interleukin [IL]-6, IL-1beta, interferon [IFN]-beta, and IFN-gamma), individually
      and in combinations, for the upregulation of MSC PGE2 secretion and attenuation
      of macrophage secretion of tumor necrosis factor (TNF)-alpha, a pro-inflammatory
      molecule, by activated-MSC conditioned medium (CM). We used multivariable linear
      regression (MLR) and analysis of covariance to determine differences in functions
      of optimal factors on monolayer MSCs and alginate-encapsulated MSCs (eMSCs). The
      screen revealed that LPS and IL-1beta potently activated monolayer MSCs to
      enhance PGE2 production and attenuate macrophage TNF-alpha. Activation by LPS and
      IL-1beta together synergistically increased MSC PGE2, but did not synergistically
      reduce macrophage TNF-alpha. MLR and covariate analysis revealed that macrophage
      TNF-alpha was strongly dependent on the MSC activation factor, PGE2 level, and
      macrophage donor but not MSC culture format (monolayer versus encapsulated). The
      results demonstrate the feasibility and utility of using statistical approaches
      for higher throughput cell analysis. This approach can be extended to develop
      activation schemes to maximize MSC and MSC-biomaterial functions prior to
      transplantation to improve MSC therapies.

PMID- 25958838
TI  - Effects of the inhalation of the m3 receptor antagonist bencycloquidium bromide
      in a mouse cigarette smoke-induced airway inflammation model.
AB  - Bencycloquidium bromide (BCQB), a novel M3 receptor antagonist, alleviates airway
      hyperresponsiveness, inflammation, and airway remodeling in a murine model of
      asthma. The aim of this study was to investigate the anti-inflammatory activity
      of inhaled BCQB in a cigarette smoke (CS)-induced model of acute lung
      inflammation. Mice exposed to CS developed chronic obstructive pulmonary disease
      (COPD). Inhalation of BCQB suppressed the accumulation of neutrophils and
      macrophages in airways and lung and also inhibited the CS-induced increases in
      mRNA levels of keratinocyte-derived chemokine, monocyte chemotactic protein-1,
      tumor necrosis factor-alpha, and interleukin-1beta in lung and protein expression
      levels in bronchoalveolar lavage fluid. Moreover, BCQB (300 MUg/ml) inhibited the
      CS-induced changes in superoxide dismutase and myeloperoxidase activities in the
      lungs. Our study suggests that BCQB might be a potential therapy for inflammation
      in CS-induced pulmonary diseases, including COPD.

PMID- 25958839
TI  - The effect of phosphate on the nuclease activity of vanadium compounds.
AB  - The nuclease activity of VO(acac)2 (1, acac = acetylacetone) and its derivatives
      VO(hd)2 (2, hd = 3,5-heptanedione), VO(Cl-acac)2 (3, Cl-acac = 3-chloro-2,4
      pentanedione), VO(Et-acac)2 (4, Et-acac = 3-ethyl-2,4-pentanedione) and VO(Me
      acac)2 (5, Me-acac = 3-methyl-2,4-pentanedione), is studied by agarose gel
      electrophoresis, UV-visible spectroscopy, cyclic and square wave voltammetry and
      (51)V NMR. The mechanism is shown to be oxidative and associated with the
      formation of reactive oxygen species (ROS). Hydrolytic cleavage of the
      phosphodiester bond is also promoted by 1, but at much slower rate which cannot
      compete with the oxidative mechanism. The generation of ROS is much higher in the
      presence of phosphate buffer when compared with organic buffers and this was
      attributed to the formation of a mixed-ligand complex containing phosphate,
      (V(IV)O)(V(V)O)(acac)2(HnPO4(n-3)), presenting a quasi-reversible voltammetric
      behavior. The formation of this species was further observed by Electrospray
      Ionization Mass Spectrometry (ESI-MS). Phosphate being an essential species in
      most biological media, the importance of the formation of mixed-ligand species in
      other vanadium systems is emphasized. 

PMID- 25958840
TI  - Theory of Floquet band formation and local pseudospin textures in pump-probe
      photoemission of graphene.
AB  - Ultrafast materials science promises optical control of physical properties of
      solids. Continuous-wave circularly polarized laser driving was predicted to
      induce a light-matter coupled state with an energy gap and a quantum Hall effect,
      coined Floquet topological insulator. Whereas the envisioned Floquet topological
      insulator requires high-frequency pumping to obtain well-separated Floquet bands,
      a follow-up question regards the creation of Floquet-like states in graphene with
      realistic low-frequency laser pulses. Here we predict that short optical pulses
      attainable in experiments can lead to local spectral gaps and novel pseudospin
      textures in graphene. Pump-probe photoemission spectroscopy can track these
      states by measuring sizeable energy gaps and Floquet band formation on
      femtosecond time scales. Analysing band crossings and pseudospin textures near
      the Dirac points, we identify new states with optically induced nontrivial
      changes of sublattice mixing that leads to Berry curvature corrections of
      electrical transport and magnetization. 

PMID- 25958841
TI  - The mediating effect of self-efficacy in the relationship between social support
      and post-traumatic stress disorder symptoms among patients with central system
      tumors in China: a cross-sectional study.
AB  - BACKGROUND: Post-traumatic stress disorder (PTSD) is a disorder that can affect
      people following the experience of a traumatic event. Few studies have researched
      on PTSD symptoms of patients with central nervous system tumors. In this study,
      we aim to examine the association between social support and PTSD symptoms and to
      explore the mediating effect of self-efficacy in this relationship among patients
      with central nervous system tumors in China. METHODS: Questionnaires consisting
      of the Post-traumatic Stress Checklist-Civilian Version, the Duke-UNC Functional
      Social Support Questionnaire, the General Self-Efficacy Scale, as well as
      demographic and clinical factors were used to collect information of patients
      with central nervous system tumors in Liaoning Province, China. A total of 222
      patients (effective response rate of 66.1%) became our subjects. Hierarchical
      linear regression analyses were performed to explore the association between
      social support and PTSD symptoms and the mediating effect of self-efficacy.
      RESULTS: After adjusting for demographic characteristics and tumor type, social
      support was negatively associated with the total score of PTSD symptoms (beta = 
      0.342, P < 0.01). Social support explained 8.8% of the variance in PTSD symptoms.
      Self-efficacy was found to partially mediate the relationship between social
      support and PTSD symptoms. CONCLUSIONS: Self-efficacy partially mediated the
      relationship between social support and PTSD symptoms. Interventions focusing on
      both social support and self-efficacy might be more useful than interventions
      only targeting either of them.

PMID- 25958842
TI  - Function and regulation of self-reactive marginal zone B cells in autoimmune
      arthritis.
AB  - Polyreactive innate-type B cells account for many B cells expressing self
      reactivity in the periphery. Improper regulation of these B cells may be an
      important factor that underlies autoimmune disease. Here we have explored the
      influence of self-reactive innate B cells in the development of collagen-induced
      arthritis (CIA), a mouse model of rheumatoid arthritis. We show that splenic
      marginal zone (MZ), but not B-1 B cells exhibit spontaneous IgM reactivity to
      autologous collagen II in naive mice. Upon immunization with heterologous
      collagen II in complete Freund's adjuvant the collagen-reactive MZ B cells
      expanded rapidly, while the B-1 B cells showed a modest anti-collagen response.
      The MZ B cells were easily activated by toll-like receptor (TLR) 4 and 9-ligands
      in vitro, inducing proliferation and cytokine secretion, implying that dual
      engagement of the B-cell receptor and TLRs may promote the immune response to
      self-antigen. Furthermore, collagen-primed MZ B cells showed significant antigen
      presenting capacity as reflected by cognate T-cell proliferation in vitro and
      induction of IgG anti-collagen antibodies in vivo. MZ B cells that were deficient
      in complement receptors 1 and 2 demonstrated increased proliferation and cytokine
      production, while Fcgamma receptor IIb deficiency of the cells lead to increased
      cytokine production and antigen presentation. In conclusion, our data highlight
      self-reactive MZ B cells as initiators of the autoimmune response in CIA, where
      complement and Fc receptors are relevant in controlling the self-reactivity in
      the cells.

PMID- 25958844
TI  - Evaluation of human epidermal growth factor receptor 2 in breast cancer with a
      novel specific aptamer.

PMID- 25958845
TI  - Augmented endothelial l-arginine transport ameliorates pressure-overload-induced
      cardiac hypertrophy.
AB  - NEW FINDINGS: What is the central question of this study? What is the potential
      role of endothelial NO production via overexpression of the l-arginine
      transporter, CAT1, as a mitigator of cardiac hypertrophy? What is the main
      finding and its importance? Augmentation of endothelium-specific l-arginine
      transport via CAT1 can attenuate pressure-overload-dependent cardiac hypertrophy
      and fibrosis. Our findings support the conclusion that interventions that improve
      endothelial l-arginine transport may provide therapeutic utility in the setting
      of myocardial hypertrophy. Such modifications may be introduced by exercise
      training or locally delivered gene therapy, but further experimental and clinical
      studies are required. Endothelial dysfunction has been postulated to play a
      central role in the development of cardiac hypertrophy, probably as a result of
      reduced NO bioavailability. We tested the hypothesis that increased endothelial
      NO production, mediated by increased l-arginine transport, could attenuate
      pressure-overload-induced cardiac hypertrophy. Echocardiography and blood
      pressure measurements were performed 15 weeks after transverse aortic
      constriction (TAC) in wild-type (WT) mice (n = 12) and in mice with endothelium
      specific overexpression of the l-arginine transporter, CAT1 (CAT+; n = 12).
      Transverse aortic constriction induced greater increases in heart weight to body
      weight ratio in WT (by 47%) than CAT+ mice (by 25%) compared with the respective
      controls (P <= 0.05). Likewise, the increase in left ventricular wall thickness
      induced by TAC was significantly attenuated in CAT+ mice (P = 0.05). Cardiac
      collagen type I mRNA expression was greater in WT mice with TAC (by 22%; P =
      0.03), but not in CAT+ mice with TAC, compared with the respective controls.
      Transverse aortic constriction also induced lesser increases in beta-myosin heavy
      chain mRNA expression in CAT+ mice compared with WT (P <= 0.05). Left ventricular
      systolic pressure after TAC was 36 and 39% greater in WT and CAT+ mice,
      respectively, compared with the respective controls (P <= 0.001). Transverse
      aortic constriction had little effect on left ventricular end-diastolic pressure
      in both genotypes. Taken together, these data indicate that augmenting
      endothelial function by overexpression of l-arginine transport can attenuate
      pressure-overload-induced cardiac hypertrophy.

PMID- 25958843
TI  - The role of nuclear receptors in regulation of Th17/Treg biology and its
      implications for diseases.
AB  - Nuclear receptors in the cell play essential roles in environmental sensing,
      differentiation, development, homeostasis,and metabolism and are thus highly
      conserved across multiple species. The anti-inflammatory role of nuclear
      receptors in immune cells has recently gained recognition. Nuclear receptors play
      critical roles in both myeloid and lymphoid cells, particularly in helper CD41 T
      cell type 17 (Th17) and regulatory T cells (Treg). Th17 and Treg are closely
      related cell fates that are determined by orchestrated cytokine signaling. Recent
      studies have emphasized the interactions between nuclear receptors and the known
      cytokine signals and how such interaction affects Th17/Treg development and
      function.This review will focus on the most recent discoveries concerning the
      roles of nuclear receptors in the context of therapeutic applications in
      autoimmune diseases.

PMID- 25958846
TI  - A highly-ordered 3D covalent fullerene framework.
AB  - A highly-ordered 3D covalent fullerene framework is presented with a structure
      based on octahedrally functionalized fullerene building blocks in which every
      fullerene is separated from the next by six functional groups and whose
      mesoporosity is controlled by cooperative self-assembly with a liquid-crystalline
      block copolymer. The new fullerene-framework material was obtained in the form of
      supported films by spin coating the synthesis solution directly on glass or
      silicon substrates, followed by a heat treatment. The fullerene building blocks
      coassemble with a liquid-crystalline block copolymer to produce a highly ordered
      covalent fullerene framework with orthorhombic Fmmm symmetry, accessible 7.5 nm
      pores, and high surface area, as revealed by gas adsorption, NMR spectroscopy,
      small-angle X-ray scattering (SAXS), and TEM. We also note that the 3D covalent
      fullerene framework exhibits a dielectric constant significantly lower than that
      of the nonporous precursor material. 

PMID- 25958847
TI  - Longitudinal study of circulating miR-122 in a rat model of non-alcoholic fatty
      liver disease.
AB  - BACKGROUND: Circulating microRNAs (miRs) may be promising biomarkers for several
      diseases. We previously found that miR-122 can function as a biomarker for non
      alcoholic fatty liver disease (NAFLD). However, little is known regarding the
      time course of circulating miR-122 levels during the development of NAFLD. Here,
      we examined circulating miR-122 levels using a rat model of NAFLD. METHODS: To
      clarify changes in serum levels of miR-122 during development of NAFLD,
      experimental rats were fed a high-fat diet (HFD) for 2-10 weeks, while control
      rats received standard chow. Serum and liver tissue was collected from all
      animals at 2, 6, and 10 weeks of feeding. Clinical laboratory parameters
      (cholesterol, TG, AST, ALT, NEFA) were determined by biochemistry analyzer.
      Hepatic lipid accumulation was estimated by Oil red O staining. Circulating miR
      122 levels were then measured by real-time polymerase chain reaction. RESULTS:
      Over the 10 weeks of feeding, body weight, total liver lipids, and liver and
      serum triacylglycerol were increased in the HFD group compared to the control
      group. However, no significant changes in serum alanine aminotransferase activity
      were observed, suggesting that NAFLD status was mild. In contrast, we observed
      drastic up-regulation of circulating miR-122 levels. Our findings suggest that
      serum miR-122 level is indeed useful for assessing early NAFLD and might be
      superior to clinical markers traditionally used to monitor hepatic disease.

PMID- 25958848
TI  - The relationship between the high-density lipoprotein (HDL)-associated
      sphingosine-1-phosphate (S1P) and coronary in-stent restenosis.
AB  - BACKGROUND: High-density lipoprotein (HDL)-associated sphingosine-1-phosphate
      (S1P) contributed to several beneficial effects in the cardiovascular system. We
      explored the relationship between the HDL-S1P concentrations and coronary in
      stent restenosis (ISR). METHODS: Fifty consecutive patients with ISR and 50
      normal control subjects were included. The serum S1P, HDL-S1P and clinical data
      were collected to explore the relationships between these parameters and ISR.
      RESULTS: The patients with ISR had significantly lower concentrations of serum
      S1P (96.10 +/- 26.33 vs. 113.40 +/- 32.72; P = 0.004) and HDL-S1P (32.81 +/-
      10.02 vs. 42.72 +/- 11.75; P < 0.001). All included patients were divided into
      four quartiles based on their concentrations of HDL-S1P: Quartile 1 (18.63-28.51
      ng/ml), Quartile 2 (28.62-37.28 ng/ml), Quartile 3 (37.35-45.27 ng/ml), and
      Quartile 4 (45.59-79.36 ng/ml). The rates of ISR were 84%, 48%, 40% and 28%,
      respectively. The patients in Quartile 1 exhibited significantly higher rates of
      ISR compared with the other groups (P = 0.001). A multivariate stepwise logistic
      regression analysis indicated that HDL-S1P (OR = 0.846, 95% CI = 0.767-0.932, P =
      0.001) was an independent predictor of ISR. An ROC analysis indicated that HDL
      S1P = 30.37 ng/ml and had a 90% sensitivity and a 52% specificity in predicting
      ISR. CONCLUSIONS: HDL-S1P is an independent predictor of ISR, and patients with
      higher concentrations of HDL-S1P have a low risk of ISR.

PMID- 25958849
TI  - Two-photon voltmeter for measuring a molecular electric field.
AB  - We present a new approach for determining the strength of the dipolar solute
      induced reaction field, along with the ground- and excited-state electrostatic
      dipole moments and polarizability of a solvated chromophore, using exclusively
      one-photon and two-photon absorption measurements. We verify the approach on two
      benchmark chromophores N,N-dimethyl-6-propionyl-2-naphthylamine (prodan) and
      coumarin 153 (C153) in a series of toluene/dimethyl sulfoxide (DMSO) mixtures and
      find that the experimental values show good quantitative agreement with
      literature and our quantum-chemical calculations. Our results indicate that the
      reaction field varies in a surprisingly broad range, 0-10(7)  V cm(-1) , and that
      at close proximity, on the order of the chromophore radius, the effective
      dielectric constant of the solute-solvent system displays a unique functional
      dependence on the bulk dielectric constant, offering new insight into the close
      range molecular interaction. 

PMID- 25958850
TI  - A Retrospective Study of Stage I to IIIa Lung Adenocarcinoma After Resection:
      What Is the Optimal Adjuvant Modality for Patients With an EGFR Mutation?
AB  - We retrospectively reviewed a total of 257 stage I to IIIa lung adenocarcinoma
      after resection, tested them for the epidermal growth factor receptor (EGFR)
      mutation, and analyzed the effect of perioperative treatment on survival. The
      results showed that in patients with an EGFR mutation, adjuvant EGFR-tyrosine
      kinase inhibitor monotherapy after complete resection significantly prolongs
      disease-free survival compared with adjuvant chemotherapy and/or radiotherapy.
      BACKGROUND: Adjuvant cisplatin-based chemotherapy improves non-small-cell lung
      cancer (NSCLC) 5-year survival rates after resection. However, adjuvant epidermal
      growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) efficacy and the
      optimal adjuvant treatment are unclear. PATIENTS AND METHODS: The clinical
      records of patients tested for EGFR mutation after complete NSCLC resection were
      reviewed and tested for significance; EGFR mutation and adjuvant therapy effects
      on survival were assessed using univariate and Cox regression analyses. RESULTS:
      We enrolled 257 patients (stage I, 126; stage II-IIIa, 131); 138 had EGFR
      mutation. EGFR mutation status was unrelated to recurrence (hazard ratio [HR],
      0.83; 95% confidence interval [CI], 0.572-1.204; P = .326) or death (HR, 0.679;
      95% CI, 0.406-1.136; P = .14). Thirty-one patients with EGFR mutation received
      adjuvant EGFR-TKIs; most (87.1%) received EGFR-TKI monotherapy. Patients who
      received adjuvant EGFR-TKIs had longer disease-free survival (DFS) than those who
      did not (P = .033) or received conventional adjuvant chemotherapy (P = .038).
      Adjuvant EGFR-TKIs did not affect overall survival (OS; P = .258), although the
      recipients had better 3-year OS (92.5% vs. 81%). Eight patients who received
      adjuvant EGFR-TKI developed disease recurrence, which occurred in 7 patients
      during adjuvant treatment. In the adjuvant EGFR-TKI group patients with a primary
      tumor EGFR mutation, EGFR mutation in the corresponding metastatic lymph nodes
      did not affect DFS, but patients who received EGFR-TKI after recurrence had
      longer progression-free survival (P = .087). CONCLUSION: In patients with an EGFR
      mutation, adjuvant EGFR-TKI monotherapy after complete resection significantly
      prolongs DFS compared with adjuvant chemotherapy and/or radiotherapy.

PMID- 25958852
TI  - Retraction: Elevated plasma levels of betatrophin in women with gestational
      diabetes mellitus.

PMID- 25958851
TI  - Complete evaluation of adrenal tumours in a tertiary care institution in
      Thuringia, Germany.
AB  - INTRODUCTION AND OBJECTIVE: Adrenal tumours, mainly incidentalomas, are an
      increasingly common clinical and diagnostic challenge. The aim of the present
      study was the retrospective evaluation of all patients with adrenal tumours
      treated in our university department from 1.1.1999-31.12.2013 PATIENTS AND
      METHODS: 187 patients (108 females: 79 males, mean age 57.7 years) were found to
      have adrenal tumours in our institution during the study period. All patients
      underwent basic and, when indicated, advanced analytical testing for hormonal
      activity. Tumours were classified according to patients' gender, age at
      diagnosis, tumour localization and size, as well as benignity and malignancy when
      postinterventional histopathological examination was conducted. RESULTS: 134
      (71.7%) patients had non-hormone secreting tumours, 17 (9.1%) pheochromocytoma,
      13 (7.0%) Conn-syndrome, 13 (7.0%) adrenal Cushing's disease, 1 congenital
      adrenal hyperplasia and 2 sexual hormone-secreting tumours. 7 (3.7%) tumours
      could not be definitively classified due to unclear or marginal test-results.
      Cushing's disease was more prevalent in females (11 females: 2 males). 163 (87.2%
      of the total cohort) tumours were unilateral [95 (50.8%) left; 68 (36.4%) right]
      and 24 (12.8%) were bilateral. Tumour size was <3 cm in 109 (58.3%), 3-6 cm in 63
      (33.7%) and >6 cm in 15 (8.0%) patients. 60 (32.1%) patients underwent
      adrenalectomy, thereof 88.9% of the patients with hormonally active tumours,
      while 8 (4.3%) were evaluated with ultrasound-guided biopsy. Malignancy was
      confirmed in 10 individuals (5.3%; 3 non-functioning tumours, 3
      pheochromocytomas, 2 Cushing's patients and 2 sexual-hormone secreting tumours),
      while 2 surgical specimens with histopathological diagnosis of pheochromocytoma
      showed signs of malignant changes. Benignity was histopathologically confirmed in
      55 patients. CONCLUSIONS: The prevalence of detected adrenal tumours is rising
      due to widely available and applied abdominal imaging procedures. The vast
      majority of them are benign, of small size (<3 cm) and hormonally inactive.
      Adrenalectomy is the therapeutic method of choice in big and/or confirmed hormone
      secreting tumours.

PMID- 25958853
TI  - Helicene-Grafted Silica Nanoparticles Capture Hetero-Double-Helix Intermediates
      during Self-Assembly Gelation.
AB  - A mixture of a pseudoenantiomeric ethynylhelicene (M)-tetramer and a (P)-pentamer
      forms a hetero-double-helix in a solution, which self-assembles and gelates
      solvents. When gelation was conducted in the presence of chiral silica (P)
      nanoparticles grafted with (P)-helicene, the resulting hetero-double-helix
      intermediate was adsorbed on the (P)-nanoparticles, and was removed from the
      solution by aggregation and precipitation. The resulting precipitates contained
      only the hetero-double-helix, not random coil or clusters of the hetero-double
      helix. (P)-Nanoparticles did not extract the hetero-double-helix from the self
      assembly gels. The hetero-double-helix was then isolated by liberating it from
      the precipitates in 2-bromopropionic acid, and was crystallized from the
      solution. The crystalline hetero-double-helices were isolated for several other
      combinations of pseudoenantiomeric ethynylhelicene oligomers. 

PMID- 25958854
TI  - Natural Magnetite: an efficient catalyst for the degradation of organic
      contaminant.
AB  - Iron (hydr)oxides are ubiquitous earth materials that have high adsorption
      capacities for toxic elements and degradation ability towards organic
      contaminants. Many studies have investigated the reactivity of synthetic
      magnetite, while little is known about natural magnetite. Here, we first report
      the reactivity of natural magnetites with a variety of elemental impurities for
      catalyzing the decomposition of H2O2 to produce hydroxyl free radicals (*OH) and
      the consequent degradation of p-nitrophenol (p-NP). We observed that these
      natural magnetites show higher catalytic performance than that of the synthetic
      pure magnetite. The catalytic ability of natural magnetite with high phase purity
      depends on the surface site density while that for the magnetites with
      exsolutions relies on the mineralogical nature of the exsolved phases. The
      pleonaste exsolution can promote the generation of *OH and the consequent
      degradation of p-NP; the ilmenite exsolution has little effect on the
      decomposition of H2O2, but can increase the adsorption of p-NP on magnetite. Our
      results imply that natural magnetite is an efficient catalyst for the degradation
      of organic contaminants in nature.

PMID- 25958857
TI  - Modelling and determination of metabolic pools by stable carbon isotopes in the
      avian duodenal mucosa and albumen.
AB  - Stable isotope analyses have helped in assessing dietary switches if the diet
      undergoes metabolic alteration (isotopic exchange). However, when considering the
      effects over time of switching from one diet to another, one can assess how
      quickly the new diet is incorporated into tissues via the isotopic renewal or
      incorporation rate, or turnover. Turnover is obtained using exponential curves
      that fit the original data, allowing the determination of practical order
      parameters such as the half-life (T) and the turnover constant (k). Researchers
      have found that metabolic incorporation can be fractionated. The resulting
      fractions, called metabolic pools, are identified using the linearization of the
      isotopic exchange model and its linear fit. This fractionation methodology is
      still not well defined. The objective of this study was to assess the behaviour
      of the metabolic renewal rate (turnover) in fractionated form, explain the
      theory, and apply it to data from the avian duodenal mucosa and albumen. We
      concluded that the duodenal mucosa has one metabolic pool, with a half-life of
      1.23 days, and that the albumen has two metabolic pools, with half-lives of 1.89
      and 6.32 days. 

PMID- 25958855
TI  - HIV-1 drug discovery: targeting folded RNA structures with branched peptides.
AB  - Human immunodeficiency virus type 1 (HIV-1) is an RNA virus that is prone to high
      rates of mutation. While the disease is managed with current antiretroviral
      therapies, drugs with a new mode of action are needed. A strategy towards this
      goal is aimed at targeting the native three-dimensional fold of conserved RNA
      structures. This perspective highlights medium-sized peptides and peptidomimetics
      used to target two conserved RNA structures of HIV-1. In particular, branched
      peptides have the capacity to bind in a multivalent fashion, utilizing a large
      surface area to achieve the necessary affinity and selectivity toward the target
      RNA. 

PMID- 25958859
TI  - The Jahn-Teller effect in the presence of partial isotopic substitution: the
      B(1)E'' state of NH2D and NHD2.
AB  - Rotationally resolved resonance enhanced multiphoton ionisation spectra of the
      B(1)E'' state of NH2D are presented and analysed. The analysis indicates a small
      (34.9 cm(-1)) lifting of the vibronic degeneracy of the zero point level,
      approximately equal in sign but opposite in magnitude to the splitting observed
      in NHD2 in previous work. This observation is consistent with previous
      measurements on systems with partial isotopic substitution subject to a mild Jahn
      Teller effect. A model is developed to calculate the splitting induced by
      asymmetric isotopic substitution of a degenerate electronic state, based on a
      harmonic force field with linear and quadratic Jahn-Teller terms added. The force
      field is developed in internal co-ordinates to allow the same parameters to be
      used to calculate the pattern of vibronic levels for all four isotopologues. The
      lifting of the degeneracy of the zero point level on asymmetric substitution
      comes from the quadratic Jahn-Teller effect; the linear term does not lift the
      degeneracy.

PMID- 25958858
TI  - GPRC6a is not required for the effects of a high-protein diet on body weight in
      mice.
AB  - OBJECTIVE: The G-protein coupled receptor family C group 6 member A (GPRC6A) is
      activated by proteinogenic amino acids and may sense amino acids in the
      gastrointestinal tract and the brain. The study investigated whether GPRC6A was
      necessary for the effects of low- and high-protein diets on body weight and food
      intake in mice. METHODS: The role of GPRC6A in mediating the effects of a low
      protein diet on body weight was investigated in GPRC6a knockout (GPRC6a-KO) and
      wild-type (WT) mice fed a control diet (18% protein) or a low-protein diet (6%
      protein) for 9 days. The role of GPRC6A in mediating the effects of a high
      protein diet on body weight was investigated in GPRC6a-KO and WT mice fed a
      control diet (18% protein) or a high-protein diet (50% protein) for 5 weeks.
      RESULTS: A high-protein diet reduced body weight gain and food intake compared
      with a control diet in both WT and GPRC6a-KO mice. A low-protein diet decreased
      body weight gain in GPRC6a-KO mice. CONCLUSIONS: GPRC6A was not necessary for the
      effects of a low- or high-protein diet on body weight and likely does not play a
      role in protein-induced satiety.

PMID- 25958862
TI  - Temporal changes of fractionation index caused by changes in the large size of
      ablated particles in laser ablation-inductively coupled plasma mass spectrometry.
AB  - To elucidate mechanisms of elemental fractionation that are observed in laser
      ablation-inductively coupled plasma mass spectrometry, the relative intensities
      of 34 elements, each normalized by a Ca internal standard, were measured every
      minute during a 10-min laser ablation of an NIST 610 glass standard. Temporal
      changes in the fractionation index (FI) were obtained by dividing the relative
      intensity of every minute by that of the first minute. The particles generated by
      laser ablation were collected on a filter every minute, and they were observed
      using scanning electron microscopy to investigate changes in the large size of
      particles. Large variations among the large size of particles were observed using
      single-site mode and under 1.0 mm defocus conditions. The 34 measured elements
      were classified into two groups, depending on their observed FI variation. The FI
      variation was rationalized by elemental behavior due to changes in the large size
      of ablated particles introduced into the ICP.

PMID- 25958863
TI  - Study of the roles of chemical modifiers in determining boron using graphite
      furnace atomic absorption spectrometry and optimization of the temperature
      profile during atomization.
AB  - The measurement conditions for determining boron using graphite furnace-atomic
      absorption spectrometry (GF-AAS) were investigated. Differences in the boron
      absorbance profiles were found using three different commercially available GF
      AAS instruments when the graphite atomizers in them were not tuned. The boron
      absorbances found with and without adjusting the graphite atomizers suggested
      that achieving an adequate absorbance for the determination of boron requires a
      sharp temperature profile that overshoots the target temperature during the
      atomization process. Chemical modifiers that could improve the boron absorbance
      without the need for using coating agents were tested. Calcium carbonate improved
      the boron absorbance but did not suppress variability in the peak height.
      Improvement of boron absorbance was comparatively less using iron nitrate or
      copper nitrate than using calcium carbonate, but variability in the peak height
      was clearly suppressed using iron nitrate or copper nitrate. The limit of
      detection was 0.0026 mg L(-1) when iron nitrate was used. It appears that iron
      nitrate is a useful new chemical modifier for the quick and simple determination
      of boron using GF-AAS.

PMID- 25958860
TI  - Major dietary patterns and carotid intima-media thickness in Bangladesh.
AB  - OBJECTIVE: Carotid intima-media thickness (IMT) is a validated surrogate marker
      of preclinical atherosclerosis and is predictive of cardiovascular morbidity and
      mortality. Research on the association between IMT and diet, however, is lacking,
      especially in low-income countries or low-BMI populations. DESIGN: Cross
      sectional analysis. Dietary intakes were measured using a validated, thirty-nine
      item FFQ at baseline cohort recruitment. IMT measurements were obtained from 2010
      2011. SETTING: Rural Bangladesh. SUBJECTS: Participants (n 1149) randomly
      selected from the Health Effects of Arsenic Longitudinal Study, an ongoing,
      population-based, prospective cohort study established in 2000. Average age at
      IMT measurement was 45.5 years. RESULTS: Principal component analysis of reported
      food items yielded a 'balanced' diet, an 'animal protein' diet and a 'gourd and
      root vegetable' diet. We observed a positive association between the gourd/root
      vegetable diet and IMT, as each 1 sd increase in pattern adherence was related to
      a difference of 7.74 (95 % CI 2.86, 12.62) MUm in IMT (P<0.01), controlling for
      age, sex, total energy intake, smoking status, BMI, systolic blood pressure and
      diabetes mellitus diagnoses. The balanced pattern was associated with lower IMT (
      4.95 (95 % CI -9.78, -0.11) MUm for each 1sd increase of adherence; P=0.045).
      CONCLUSIONS: A gourd/root vegetable diet in this Bangladeshi population
      positively correlated with carotid IMT, while a balanced diet was associated with
      decreased IMT.

PMID- 25958864
TI  - Double-sided Microfluidic Device for Speciation Analysis of Iron in Water
      Samples: Towards Greener Analytical Chemistry.
AB  - Microfluidics minimize the amounts of reagents and generate less waste. While
      microdevices are commonly single-sided, producing a substrate with microchannels
      on multiple surfaces would increase their usefulness. Herein, a
      polymethymethacrylate substrate incorporating microchannel structures on two
      sides was sandwiched between two polydimethylsiloxane sheets to create a multi
      analysis device, which was used for the spectrophotometric analysis of the
      ferrous ion (Fe(2+)) and the ferric ion (Fe(3+)), by utilizing colorimetric
      detection. To monitor the signals from both channel networks, dual optical
      sensors were integrated into the system. The linear ranges for Fe(2+) and Fe(3+)
      analyses were 0.1 - 20 mg L(-1) (R(2) = 0.9988) and 1.0 - 40 mg L(-1) (R(2) =
      0.9974), respectively. The detection limits for Fe(2+) and Fe(3+) were 0.1 and
      0.5 mg L(-1), respectively. The percent recoveries of Fe(2+) and Fe(3+) were 93.5
      - 104.3 with an RSD < 8%. The microdevice demonstrated capabilities for
      simultaneous analysis, low waste generation (7.2 mL h(-1)), and high sample
      throughput (180 h(-1)), making it ideal for greener analytical chemistry
      applications. 

PMID- 25958865
TI  - Fast and Efficient Separation and Determination of UV-absorbing Amino Acids,
      Nucleobases, and Creatinine Using a Carboxy-functionalized Cation-exchange
      Column.
AB  - This paper presents a new HPLC technique for the determination of biogenic
      cations such as amino acids and nucleobases, using a weak-acid cation-exchange
      column. Fourteen analytes, five amino acids and seven bases in addition to
      creatinine and creatine, were separated in 12 min by means of a two-liquid
      gradient elution with UV detection. The newly released column packed with a
      carboxy-functionalized polymethacrylate resin could give excellent selectivity to
      the organic cations of interest, although such a column is in general suitable
      for the separation of inorganic common cations. The chromatographic intra-day
      repeatability was very good with RSDs less than 0.4%, and the quantitation
      precision based on peak area intensities was also good with RSDs less than 5% for
      all analytes. The linear calibration lines for quantitation ranged between 5 and
      500 MUM on 20-MUL injections with R(2) more than 0.9990. Since the method could
      provide concentration data of urinary creatinine and some metabolites
      simultaneously, for example, the urinary phenylalanine/creatinine ratios for
      phenylketonuria of inborn errors of metabolism were simply determined through one
      chromatographic run. The ratios for patients were significantly higher than those
      for controls. We found that the new weak-acid cation-exchange column was suitable
      for the separation of organic cations as well as inorganic cations.

PMID- 25958866
TI  - Quantification of Lipopeptides Using High-performance Liquid Chromatography with
      Fluorescence Detection after Derivatization.
AB  - A highly sensitive and selective high-performance liquid chromatographic (HPLC)
      method has been developed for the determination of microbial lipopeptides of
      fluorescent derivatization with 1-bromoacetylpyrene to overcome the limitations
      of trace detection of lipopeptides in aqueous solutions. The derivatization of
      lipopeptides with 1-bromoacetylpyrene was conducted at 60 degrees C for 20 min
      under catalysis of triethylamine. The resulting derivative products were
      separated by HPLC and determined by a fluorescence detector. Each homolog of
      lipopeptides in samples was identified by HPLC-MS and the detection limit after
      derivatization in an aqueous solution was 2.5 MUg/mL (S/N = 3). The calibration
      curve for lipopeptides was linear in the concentration range of 0.250 - 4.00
      mg/mL. This method has adequate sensitivity and selectivity for microdetection of
      lipopeptides in aqueous solutions in mild reaction conditions, which allows this
      method to be used in the determination of trace lipopeptides in environmental
      samples and complex samples.

PMID- 25958867
TI  - Automatic On-line Solid-phase Extraction-Electrothermal Atomic Absorption
      Spectrometry Exploiting Sequential Injection Analysis for Trace Vanadium, Cadmium
      and Lead Determination in Human Urine Samples.
AB  - A fully automated sequential injection column preconcentration method for the on
      line determination of trace vanadium, cadmium and lead in urine samples was
      successfully developed, utilizing electrothermal atomic absorption spectrometry
      (ETAAS). Polyamino-polycarboxylic acid chelating resin (Nobias chelate PA-1)
      packed into a handmade minicolumn was used as a sorbent material. Effective on
      line retention of chelate complexes of analytes was achieved at pH 6.0, while the
      highest elution effectiveness was observed with 1.0 mol L(-1) HNO3 in the reverse
      phase. Several analytical parameters, like the sample acidity, concentration and
      volume of the eluent as well as the loading/elution flow rates, have been
      studied, regarding the efficiency of the method, providing appropriate conditions
      for the analysis of real samples. For a 4.5 mL sample volume, the sampling
      frequency was 27 h(-1). The detection limits were found to be 3.0, 0.06 and 2.0
      ng L(-1) for V(V), Cd(II) and Pb(II), respectively, with the relative standard
      deviations ranging between 1.9 - 3.7%. The accuracy of the proposed method was
      evaluated by analyzing a certified reference material (Seronorm(TM) trace
      elements urine) and spiked urine samples.

PMID- 25958868
TI  - On-line Determination of Zinc in Water and Biological Samples after Its
      Preconcentration onto Zincon Anchored Polyurethane Foam.
AB  - A fast and sensitive on-line procedure for the determination of zinc in water and
      biological samples was developed. Zinc was preconcentrated in a mini-column
      packed with polyurethane foam (PUF) chemically modified with zincon via -N=N-
      bonding. The optimal conditions for preconcentration were pH 8.5 and sample flow
      rate of 4.0 mL min(-1). Quantitative desorption of Zn(II) was obtained by 0.1 mol
      L(-1) hydrochloric acid and subsequent spectrophotmetric determination using 4-(2
      pyridylazo)-resorcinol at 498 nm. The obtained detection limit was found to be
      3.0 ng mL(-1), precision (RSD) was 4.8 and 6.7% at 20 and 110 ng mL(-1),
      respectively, for 60 s preconcentration time and enrichment factor was 31. The
      linearity range was from 10 to 120 ng mL(-1) and maximum sample throughput was 20
      h(-1). Finally, the method was successfully applied to the determination of zinc
      in tap water, Nile River water and human urine samples with RSD in the range of
      1.1 - 8.3%.

PMID- 25958869
TI  - Fabrication of Fe3O4 Nanoparticle-coalesced Hydroxylated Multi-walled Carbon
      Nanotubes for the Analysis of Strychnine in Human Serum.
AB  - A magnetic carbon nanomaterial for Fe3O4-modified hydroxylated multi-walled
      carbon nanotubes (Fe3O4-MWCNTs-OH) was prepared by the aggregating effect of
      Fe3O4 nanoparticles on MWCNTs-OH, and this material was combined with high
      performance liquid chromatography (HPLC)/photodiode array detector (PAD) to
      determine strychnine in human serum samples. Some important parameters that could
      influence the extraction efficiency of strychnine were optimized, including the
      extraction time, amounts of Fe3O4-MWCNTs-OH, pH of sample solution, desorption
      solvent and desorption time. Under optimal conditions, the recoveries of spiked
      serum samples were between 98.3 and 102.7%, and the relative standard deviations
      (RSDs) ranged from 0.9 to 5.3%. The correlation coefficient was 0.9997. The LODs
      and LOQs of strychnine were 6.2 and 20.5 ng mL(-1), at signal-to-noise ratios of
      3 and 10, respectively. These experimental results showed that the proposed
      method is feasible for the analysis of strychnine in serum samples.

PMID- 25958870
TI  - Developing a new micro cloud point extraction method for simultaneous
      preconcentration and spectrophotometric determination of uranium and vanadium in
      brine.
AB  - A fast, simple, and economical method was developed for simultaneous
      spectrophotometric determination of uranium(VI) and vanadium(V) in water samples
      based on micro cloud point extraction (MCPE) at room temperature. This is the
      first report on the simultaneous extraction and determination of U(VI) and V(V).
      In this method, Triton X114 was employed as a non-ionic surfactant for the cloud
      point procedure and 4-(2-pyridylazo) resorcinol (PAR) was used as the chelating
      agent for both analytes. To reach the cloud point at room temperature, the MCPE
      procedure was carried out in brine. The factors influencing the extraction
      efficiency were investigated and optimized. Under the optimized condition, the
      linear calibration curve was found to be in the concentration range between 100 -
      750 and 50 - 600 MUg L(-1) for U(VI) and V(V), respectively, with a limit of
      detection of 17.03 MUg L(-1) (U) and 5.51 MUg L(-1) (V). Total analysis time
      including microextraction was less than 5 min.

PMID- 25958871
TI  - A novel analysis method for lactate dehydrogenase activity in serum samples based
      on fluorescence capillary analysis.
AB  - Based on fluorescence capillary analysis technology, a method for quantitating
      lactate dehydrogenase (LDH) activity in a micro-volume sample was developed.
      Sample and reagent consumptions were merely 2 and 16 MUL per time, respectively.
      The optimized test conditions were as follows. The reaction reagent consisted of
      0.10 M phosphate buffer (pH 6.5), 0.30 mM NADH and 1.20 mM pyruvate. NADH
      standard was prepared with a phosphate buffer of pH 8.0, and its linear response
      was controlled in 0.05 - 0.30 mM. LDH standards containing 2.0 mM PEG could
      exhibit long-term stability. Under the optimized conditions, a linear response
      for LDH from 50 to 1200 U L(-1) and a detection limit of 31 U L(-1) were obtained
      with good precision (RSD: 2.1 - 2.2%, n = 10) and better recovery of 96 - 105%.
      The method's characteristics was high sensitivity, low consumptions, simple
      operations, good precision and reliability, lending itself to the miniaturization
      of fluorophotometer which transformed into a bedside instrument in the hospital. 

PMID- 25958872
TI  - Comparison of Candidate Pairs of Hydrolytic Enzymes for Spectrophotometric-dual
      enzyme-simultaneous-assay.
AB  - Spectrophotometric-dual-enzyme-simultaneous-assay (SDESA) for enzyme-linked
      immunosorbent-assay (ELISA) of two components in one well is a patented platform
      when a special pair of labels is accessible. With microplate readers, alkaline
      phosphatase on 4-nitro-1-naphthylphosphate (4NNPP) served as label A; Pseudomonas
      aeruginosa arylsulfatase (PAAS) and acetylcholinesterase (AChE) on their
      substrates derived from 4-nitrophenol/analogue served as candidate label B, and
      were compared for SDESA with an engineered alkaline phosphatase of Eschrichia
      coli (ECAP). For SDESA, the interference from overlapped absorbance was corrected
      based on linear additivity of absorbance to derive initial rates reflected by
      absorbance change at 450 nm for ECAP and at 405 nm for PAAS or AChE, after the
      correction of spontaneous hydrolysis. For SDESA with ECAP, AChE already had
      sufficient activity in an optimized buffer; PAAS was more favorable for substrate
      stability and product absorbance except for lower activity. Therefore, PAAS
      engineered for sufficient activity plus alkaline phosphatase is absorbing for
      ELISA via SDESA. 

PMID- 25958873
TI  - Amperometric Determination of Ascorbic Acid on an Au Electrode Modified by a
      Composite Film of Poly(3,4-ethylenedioxythiophene) and Superconductive Carbon
      Black.
AB  - A new composite film-modified electrode was prepared by the electropolymerisation
      of poly(3,4-ethylenedioxythiophene) (PEDOT) and superconductive carbon black
      (SCB) on a gold electrode. The PEDOT-SCB/Au electrode exhibited excellent ability
      towards the electrocatalytic oxidation of ascorbic acid, in terms of a 480 mV
      shift of the oxidation potential in the negative direction, and a dramatically
      enhanced oxidation current. Under the optimum conditions, the amperometric
      detection of ascorbic acid provided a wide linear detection range from 1.0 * 10(
      7) to 8.0 * 10(-4) M, and a detection limit of 5.0 * 10(-8) M (S/N = 2) as well
      as good reproducibility and stability.

PMID- 25958874
TI  - Synthesis of silver nanoparticle: a new analytical approach for the quantitative
      assessment of adrenaline.
AB  - Silver nanoparticle (AgNP) has been synthesized using adrenaline. Adrenaline
      readily undergoes an autoxidation reaction in an alkaline medium with the
      dissolved oxygen to form adrenochrome, thus behaving as a mild reducing agent for
      the dissolved oxygen. This reducing behavior of adrenaline when employed to
      reduce Ag(+) ions yielded a large enhancement in the intensity of absorbance in
      the visible region. Transmission electron microscopy (TEM) and X-ray diffraction
      (XRD) studies have been performed to confirm the surface morphology of AgNPs.
      Further, the metallic nanoparticles with size greater than 2 nm caused a strong
      and broad absorption band in the UV-visible spectrum called surface plasmon band
      or Mie resonance. The formation of AgNPs caused the large enhancement in the
      absorbance values with lambdamax at 436 nm through the excitation of the surface
      plasmon band. The formation of AgNPs was adopted to for the quantitative
      assessment of adrenaline using spectrophotometry with lower detection limit and
      higher precision values.

PMID- 25958875
TI  - Quantitative Analysis of Chloramphenicol in Royal Jelly by Column-switching LC
      MS/MS Using a Pretreatment Column with a Higher-pressure Capability.
AB  - An on-line pretreatment liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      system was developed for the analysis of chloramphenicol (CAP) in royal jelly. A
      novel methylcellulose-immobilized restricted access media column with a higher
      pressure capability of 60 MPa (MC-ODS HP) was developed for the effective removal
      of proteins and other compounds in the sample matrix. CAP in a sample solution
      was extracted in 2 min by the column-switching LC-MS/MS system. The system
      provides a minimum sample pretreatment along with highly sensitive and
      reproducible analysis. As a result, the limit of quantitation of CAP was 10 pg/mL
      (= 0.1 MUg/kg royal jelly) and the linear dynamic range was between 10 and 10000
      pg/mL (correlation coefficient greater than 0.999). The proposed method meets the
      requirements of regulations in EU (0.3 MUg/kg). The inter-day precision and
      accuracy of CAP at 100 pg/mL over 3 days were 4.5 and 95.4%, respectively.
      Compared with the conventional method with a pressure of below 25 MPa, the peak
      separation in the MRM chromatogram was improved by using smaller particles (1.6
      MUm) for the analytical ODS column. The LC-MS/MS system with an MC-ODS HP
      expanded the applicability of the automated pretreatment.

PMID- 25958876
TI  - Temperature-dependent Photodegradation in UV-resonance Raman Spectroscopy.
AB  - Temperature-dependent photodegradation during UV-resonance Raman spectroscopy was
      investigated. Photodegradation was quantitatively probed by monitoring the
      temporal evolution of UV-resonance Raman spectra obtained from
      bacteriochlorophyll (BChl) showing, resonance effect at a 355-nm excitation
      wavelength. At 80 K, the molecular photodecomposition rate was 5-times lower than
      that at room temperature. The decomposition rates of BChl were analyzed by the
      Arrhenius formula, indicating that the mechanism of photodegradation includes a
      thermal process having an activation energy of 1.4 kJ/mol.

PMID- 25958878
TI  - Eosinophilic annular erythema: successful response to ultraviolet B therapy.
AB  - Eosinophilic annular erythema (EAE) is a rare and relatively newly described
      eosinophil-rich dermatosis. Debate still exists as to whether it represent a
      subtype of Well syndrome or a separate disease entity. We report an 8-year-old
      boy with a 4-year history of recurrent, asymptomatic annular lesions, which were
      diagnosed after clincopathological correlation as EAE. This condition usually
      runs a relapsing and remitting course with resistance to multiple treatments.
      Prednisolone and hydroxychloroquine have been reported as successful but the
      response to these was limited in this case. Complete resolution occurred after
      treatment with ultraviolet B (UVB) therapy. To our knowledge, this is the first
      report of a favourable response of EAE to such therapy. 

PMID- 25958879
TI  - A prospective, comparative survey to investigate practitioners' satisfaction with
      a cohesive, polydensified-matrix((r)) , hyaluronic acid-based filler gel with and
      without lidocaine for the treatment of facial wrinkles.
AB  - BACKGROUND: Lidocaine-containing dermal fillers may reduce procedural pain
      compared with lidocaine-free counterparts. OBJECTIVES: To assess practitioners'
      administration experience with, and the efficacy and safety of, a cohesive,
      polydensified-matrix((r)) , hyaluronic acid-based filler containing lidocaine vs.
      its lidocaine-free counterpart. METHODS: The lidocaine-containing formulation was
      injected to one side of the face and the lidocaine-free to the other in 29
      females (30-85 years). Administered dose was appropriate to the treatment zone
      and technique varied according to zone and practitioner preference.
      Questionnaires assessed practitioners' administration experience, their
      perception of results, subject satisfaction, and product safety. RESULTS:
      Practitioners considered the formulations to be similar in terms of ejection
      force, texture, and placement. The blanching technique was used for 72% of
      subjects, and its ease was rated as "identical" for both products in 81% of
      applications and "easier" for the lidocaine-containing product in 6.9% of
      applications. Results with both formulations were "identical" for 86% of
      applications and "similar" for the remainder. In 86% of cases, practitioners
      would "certainly" consider continuing treatment with the lidocaine-containing
      formulation. All subjects were "satisfied" with treatment. Practitioners reported
      that, compared with the lidocaine-free product, subject-assessed pain with the
      lidocaine-containing product was "less prominent" for 86% and 79% of participants
      during and following treatment, respectively. Similarly, mean pain intensity was
      significantly lower for the lidocaine-containing preparation (P = 0.0001).
      Adverse events were similar for both treatments. CONCLUSIONS: The lidocaine
      containing dermal filler significantly reduced pain during and following
      treatment compared with the same preparation without lidocaine, without impact on
      administration, aesthetic outcome, or safety.

PMID- 25958880
TI  - Structural basis of non-steroidal anti-inflammatory drug diclofenac binding to
      human serum albumin.
AB  - Human serum albumin (HSA) is the most abundant protein in plasma, which plays a
      central role in drug pharmacokinetics because most compounds bound to HSA in
      blood circulation. To understand binding characterization of non-steroidal anti
      inflammatory drugs to HSA, we resolved the structure of diclofenac and HSA
      complex by X-ray crystallography. HSA-palmitic acid-diclofenac structure reveals
      two distinct binding sites for three diclofenac in HSA. One diclofenac is located
      at the IB subdomain, and its carboxylate group projects toward polar environment,
      forming hydrogen bond with one water molecule. The other two diclofenac molecules
      cobind in big hydrophobic cavity of the IIA subdomain without interactive
      association. Among them, one binds in main chamber of big hydrophobic cavity, and
      its carboxylate group forms hydrogen bonds with Lys199 and Arg218, as well as one
      water molecule, whereas another diclofenac binds in side chamber, its carboxylate
      group projects out cavity, forming hydrogen bond with Ser480. 

PMID- 25958881
TI  - Comparative physiological and proteomic analyses reveal the actions of melatonin
      in the reduction of oxidative stress in Bermuda grass (Cynodon dactylon (L).
      Pers.).
AB  - The fact of melatonin as an important antioxidant in animals led plant
      researchers to speculate that melatonin also acts in the similar manner in
      plants. Although melatonin has significant effects on alleviating stress
      triggered reactive oxygen species (ROS), the involvement of melatonin in direct
      oxidative stress and the underlying physiological and molecular mechanisms remain
      unclear in plants. In this study, we found that exogenous melatonin significantly
      alleviated hydrogen peroxide (H2O2)-modulated plant growth, cell damage, and ROS
      accumulation in Bermuda grass. Additionally, 76 proteins significantly influenced
      by melatonin during mock or H2O2 treatment were identified by gel-free proteomics
      using iTRAQ (isobaric tags for relative and absolute quantitation). Metabolic
      pathway analysis showed that several pathways were markedly enhanced by melatonin
      and H2O2 treatments, including polyamine metabolism, ribosome pathway, major
      carbohydrate metabolism, photosynthesis, redox, and amino acid metabolism. Taken
      together, this study provides more comprehensive insights into the physiological
      and molecular mechanisms of melatonin in Bermuda grass responses to direct
      oxidative stress. This may relate to the activation of antioxidants, modulation
      of metabolic pathways, and extensive proteome reprograming.

PMID- 25958882
TI  - Exposure of Wildlife to the Schmallenberg Virus in France (2011-2014): Higher,
      Faster, Stronger (than Bluetongue)!
AB  - The Schmallenberg virus (SBV) has recently emerged in Europe, causing losses to
      the domestic livestock. A retrospective analysis of serodata was conducted in
      France for estimating seroprevalence of SBV among six wildlife species from 2011
      2012 to 2013-2014, that is during the three vector seasons after the emergence of
      the SBV in France. Our objective was to quantify the exposure of wildlife to SBV
      and the potential protective effect of elevation such as previously observed for
      bluetongue. We also compared the spatiotemporal trends between domestic and wild
      animals at the level of the departments. We tested 2050 sera using competitive
      ELISA tests. Individual and population risk factors were further tested using
      general linear models among 1934 individuals. All populations but one exhibited
      positive results, seroprevalence up to 30% being observed for all species. The
      average seroprevalence did not differ between species but ranged from 0 to 90%
      according to the area and period, due to the dynamic pattern of infection.
      Seroprevalence was on average higher in the lowlands compared to areas located up
      to 800 m. Nevertheless, seroprevalence above 50% occurred in areas located up to
      1500 m. Thus, contrary to what had been observed for bluetongue during the late
      2000s in the same areas, SBV could spread to high altitudes and infect all the
      studied species. The spatial spread of SBV in wildlife did not fully match with
      SBV outbreaks reported in the domestic livestock. The mismatch was most obvious
      in mountainous areas where outbreaks in wildlife occurred on average one year
      after the peak of congenital cases in livestock. These results suggest a much
      larger spread and vector capacity for SBV than for bluetongue virus in natural
      areas. Potential consequences for wildlife dynamics are discussed.

PMID- 25958883
TI  - Development of facial sexual dimorphism in children aged between 12 and 15 years:
      a three-dimensional longitudinal study.
AB  - OBJECTIVES: To evaluate sexual dimorphism of facial form and shape and to
      describe differences between the average female and male face from 12 to 15
      years. SETTING AND SAMPLE POPULATION: Overall 120 facial scans from healthy
      Caucasian children (17 boys, 13 girls) were longitudinally evaluated over a 4
      year period between the ages of 12 and 15 years. MATERIALS AND METHODS: Facial
      surface scans were obtained using a three-dimensional optical scanner Vectra-3D.
      Variation in facial shape and form was evaluated using geometric morphometric and
      statistical methods (DCA, PCA and permutation test). Average faces were
      superimposed, and the changes were evaluated using colour-coded maps. RESULTS:
      There were no significant sex differences (p > 0.05) in shape in any age category
      and no differences in form in the 12- and 13-year-olds, as the female faces were
      within the area of male variability. From the age of 14, a slight separation
      occurred, which was statistically confirmed. The differences were mainly
      associated with size. Generally boys had more prominent eyebrow ridges, more
      deeply set eyes, a flatter cheek area, and a more prominent nose and chin area.
      CONCLUSION: The development of facial sexual dimorphism during pubertal growth is
      connected with ontogenetic allometry.

PMID- 25958885
TI  - Case of collagenous fibroma (desmoplastic fibroblastoma) with vascular
      hyperplasia in the boundary area detected by Doppler sonography and
      histopathological examination.

PMID- 25958884
TI  - Antibody response to influenza A(H1N1)pdm09 in vaccinated, serologically infected
      and unaffected pregnant women and their newborns.
AB  - OBJECTIVE: To evaluate the serological response in pregnant Danish women
      immunized during the 2009 pandemic by serologic infection or by vaccination with
      influenza A(H1N1) Pandemrix((r)) and describe levels of passively acquired
      maternal antibody in their offspring. DESIGN: Observational cohort study.
      SETTING: Department of Obstetrics, Aarhus University Hospital, Skejby, Denmark,
      October to December 2009. POPULATION: Pregnant women and their offspring METHODS:
      Serological analysis of antibodies to influenza A(H1N1)pdm09 by hemagglutination
      inhibition assay in 197 women and their offspring. Blood samples were collected
      consecutively at delivery from the mother and the umbilical cord. In a subgroup
      of 124 of the 197 women, an additional blood sample from gestational weeks 9-12
      was available for analysis. MAIN OUTCOME MEASURES: Seroconversion, geometric mean
      titer, geometric mean-fold rise and protective antibodies. RESULTS: 33 of the 124
      subgroup women (27%) seroconverted during pregnancy, 79% after vaccination and
      17% after serologic infection (p < 0.001). The geometric mean titer after
      delivery in non-vaccinated, non-serologically infected women was 17.1 (95%CI 15.7
      18.6). The geometric mean titer increased significantly after serologic infection
      with H1N1 [76.5 (95%CI 51.3-113.9), p < 0.001] and after vaccination [589.6
      (95%CI 339.3-1024.7), p < 0.001]. The geometric mean-fold rise (mother at
      delivery/mother early pregnancy) was significantly higher after vaccination [2.23
      (1.93-2.54)] than after serologic infection [1.73 (1.59-1.87), p = 0.013]. In
      newborns of vaccinated mothers, 89.5% had protective antibody levels compared
      with 15.8% in newborns of serologically infected mothers (p < 0.001).
      CONCLUSIONS: Influenza vaccination during pregnancy confers passive immunity to
      the newborn.

PMID- 25958886
TI  - Can nurses be key players in assessing early motor development using a structured
      method in the child health setting?
AB  - RATIONAL, AIMS AND OBJECTIVES: Increasing evidence highlights the importance of
      early interventions for motor disorders in children. Given the key medical role
      of the nurse within the Swedish Child Health Service (CHS), we aimed to examine
      if nurses could apply a structured assessment of early motor development at the
      child health centre to enable early identification of children at risk. METHODS:
      Structured Observation of Motor Performance in Infants (SOMP-I) assesses infant's
      level of motor development and quality of motor performance using subscales
      converted to total scores. The total score for both level and quality can then be
      plotted within the SOMP-I percentile distribution at the child's age for
      comparison with a reference population. Fifty-five infants (girls: 30) were
      assessed according to SOMP-I at three child health centres. Assessments were
      performed by nurses (n = 10) in a clinical setting; one nurse performed the
      assessment while another nurse and a physiotherapist observed. RESULTS: Agreement
      for the assessment of level as a continuous variable was excellent [intraclass
      correlation coefficient (ICC) 0.97-0.98], but was lower for quality (ICC 0.02
      0.46). When the children were categorized according to the percentile range
      categories, the assessors were in agreement for the majority of the children,
      with respect to both level (78-82%) and quality (78-87%). CONCLUSION: Despite
      brief experience with SOMP-I, the agreement was excellent when assessing the
      level of motor development, but was less satisfactory for the assessment of
      quality of motor performance. More extensive education and training may be
      necessary to improve the nurses' ability to assess quality, as this domain was an
      entirely new concept to the nurses. Further research is warranted to determine
      the applicability of SOMP-I as a standardized method for nurses to assess motor
      development within the CHS.

PMID- 25958887
TI  - Concepts of capacity and performance in assessment of functioning amongst stroke
      survivors: A comparison of the Functional Independence Measure and the
      International Classification of Functioning, Disability and Health.
AB  - OBJECTIVE: To investigate the use of concepts of capacity and performance when
      assessing functioning of stroke survivors, measured with the Functional
      Independence Measure (FIM) and the International Classification of Functioning,
      Disability and Health (ICF). METHODS: During an inpatient interdisciplinary
      rehabilitation programme for 62 subacute stroke survivors, limitations in
      speaking, walking, toileting and eating were assessed at admission and discharge
      with both the FIM and a scale based on the ICF Brief Core Set for stroke.
      Correlation between the results obtained with these 2 scales was assessed using
      Spearman's correlation coefficient. RESULTS: The level of restriction of
      functioning, defined as capacity or performance in terms of the ICF, correlated
      well with the results obtained with the FIM (0.47-0.87) . The only statistically
      significant difference was found in assessing limitations in eating, where
      assessment with the FIM had a higher correlation with the concept of capacity
      than performance (0.75 vs 0.55). The observed correlations were not associated
      with stroke severity. CONCLUSION: Even though the FIM and an ICF-based scale may
      describe limitation of functioning of stroke survivors similarly, ICF is probably
      more comprehensive in describing both capacity and performance.

PMID- 25958888
TI  - Pneumopericardium, pneumomediastinum, pneumothorax and pneumoretroperitoneum
      complicating pulmonary metastatic carcinoma in a cat.
AB  - This report describes a case of severe spontaneous tension pneumopericardium with
      concurrent pneumomediastinum, pneumothorax and retropneumoperitoneum in a cat
      presenting with dyspnoea and signs of cardiac tamponade secondary to metastatic
      pulmonary carcinoma. Spontaneous pneumopericardium is an extremely uncommon
      condition consisting of pericardial gas in the absence of iatrogenic/traumatic
      causes. In humans, it has been described secondary to pneumonia or lung abscess
      and very rarely secondary to pulmonary neoplasia. 

PMID- 25958890
TI  - Risk Matrix Integrating Risk Attitudes Based on Utility Theory.
AB  - Recent studies indicate that absence of the consideration of risk attitudes of
      decisionmakers in the risk matrix establishment process has become a major
      limitation. In order to evaluate risk in a more comprehensive manner, an approach
      to establish risk matrices that integrates risk attitudes based on utility theory
      is proposed. There are three main steps within this approach: (1) describing risk
      attitudes of decisionmakers by utility functions, (2) bridging the gap between
      utility functions and the risk matrix by utility indifference curves, and (3)
      discretizing utility indifference curves. A complete risk matrix establishment
      process based on practical investigations is introduced. This process utilizes
      decisionmakers' answers to questionnaires to formulate required boundary values
      for risk matrix establishment and utility functions that effectively quantify
      their respective risk attitudes. 

PMID- 25958889
TI  - Stage of Presentation at Initial Breast Cancer Diagnosis: Does Race Remain a
      Factor?

PMID- 25958892
TI  - Current concepts, state of the art treatment of facial paralysis.

PMID- 25958891
TI  - Persistent inter- and intraspecific gene exchange within a parallel radiation of
      caterpillar hunter beetles (Calosoma sp.) from the Galapagos.
AB  - When environmental gradients are repeated on different islands within an
      archipelago, similar selection pressures may act within each island, resulting in
      the repeated occurrence of ecologically similar species on each island. The
      evolution of ecotypes within such radiations may either result from dispersal,
      that is each ecotype evolved once and dispersed to different islands where it
      colonized its habitat, or through repeated and parallel speciation within each
      island. However, it remains poorly understood how gene flow during the divergence
      process may shape such patterns. In the Galapagos islands, three phenotypically
      similar species of the beetle genus Calosoma occur at higher elevations of
      different islands, while lowlands are occupied by a fourth species. By genotyping
      all major populations within this radiation for two nuclear and three
      mitochondrial gene fragments and seven microsatellite markers, we found strong
      support that the oldest divergence separates the highland species of the oldest
      island from the remaining species. Despite their morphological distinctness,
      highland species of the remaining islands were genetically closely related to the
      lowland population on each island and within the same magnitude as lowland
      populations sampled at different islands. Repeated evolution of highland ecotypes
      out of the lowland species appears the most likely scenario and estimates of
      geneflow rates revealed extensive admixture among ecotypes within islands, as
      well as between islands. These findings indicate that gene exchange among the
      different populations and species may have shaped the phylogenetic relationships
      and the repeated evolution of these ecotypes. 

PMID- 25958893
TI  - Contemporary management of Bell palsy.
AB  - Bell palsy (BP) is the most common diagnosis in acute and chronic facial palsy.
      Although most patients fully recover, more than one-quarter will have residual
      dysfunction. Of these, nearly half will demonstrate severe limitations in facial
      expression. Though significant attention has been paid to acute management and
      prognosis, a paucity of literature exists addressing management of the long-term
      sequelae of BP. This article describes contemporary use of physical therapy,
      injectables, and static and dynamic surgical procedures in facial reanimation of
      acute and chronic BP. 

PMID- 25958894
TI  - Facial reanimation after acoustic neuroma resection: options and timing of
      intervention.
AB  - Facial paralysis following acoustic neuroma (AN) resection can be devastating,
      but timely and strategic intervention can minimize the resulting facial
      morbidity. A central strategy in reanimating the paralyzed face after AN
      resection is to restore function of the native facial muscles using available
      facial nerves or repurposed cranial nerves, mainly the hypoglossal or masseter
      nerves. The timing of reinnervation is the single most influential factor that
      determines outcomes in facial reanimation surgery. The rate of recovery of facial
      function in the first 6 months following AN resection may be used to predict
      ultimate facial function. Patients who show no signs of recovery in the first 6
      months, even when their facial nerves are intact, recover poorly and are
      candidates for early facial reinnervation. With delay, facial muscles become
      irreversibly paralyzed. Reanimation in irreversible paralysis requires the
      transfer of functional muscle units such as the gracilis or the temporalis muscle
      tendon unit. 

PMID- 25958895
TI  - Management of Facial Paralysis due to Extracranial Tumors.
AB  - Treatment of advanced parotid or cutaneous malignancies often requires sacrifice
      of the facial nerve as well as resection of the parotid gland and surrounding
      structures. In addition to considerations regarding reinnervation and dynamic
      reanimation, reconstruction in this setting must take into account unique factors
      such as soft tissue volume deficits and the high likelihood of adjunctive
      radiation therapy. Furthermore, considerations of patient comorbidities including
      advanced age and poor long-term prognosis often influence reconstructive
      modality. The optimal reconstructive technique would provide potential for
      restoration of facial tone and voluntary movement as well as immediate
      restoration of facial support and function. Beyond considerations of facial
      movement and rest position, restoration of lost soft tissue volume is critical to
      obtain facial symmetry. To control long-term volume in the setting of adjunctive
      radiation therapy, vascularized tissue is required. In this chapter, we describe
      a comprehensive approach to the management of radical parotidectomy and similar
      facial defects that addresses these concerns and also describes management
      strategies over time. Specific techniques employed include anterolateral thigh
      free flaps, nerve grafting utilizing motor nerves to the vastus lateralis muscle,
      and orthodromic temporalis tendon transfer. Further considerations relative to
      the eye, forehead, and long-term facial refinement are also discussed. 

PMID- 25958896
TI  - Facial paralysis in children.
AB  - Facial paralysis can have devastating physical and psychosocial consequences.
      These are particularly severe in children in whom loss of emotional
      expressiveness can impair social development and integration. The etiologies of
      facial paralysis, prospects for spontaneous recovery, and functions requiring
      restoration differ in children as compared with adults. Here we review
      contemporary management of facial paralysis with a focus on special
      considerations for pediatric patients. 

PMID- 25958897
TI  - Lengthening temporalis myoplasty: a surgical tool for dynamic labial commissure
      reanimation.
AB  - Lengthening temporalis myoplasty (LTM), first described by Labbe in 1997, ensures
      the transfers of the entire temporal muscle from the coronoid process to the
      upper half of the lip without interposition of aponeurotic tissue. The temporal
      muscle changes function because it is entirely mobilized toward another effector:
      the labial commissure. Thanks to brain plasticity, the muscle loses its chewing
      function, and after 6 months of speech rehabilitation it acquires its new smiling
      function. We describe technical points especially the coronoid process approaches
      both through an upper temporal fossa approach and a lower nasolabial fold
      approach. Rehabilitation starts 3 weeks after the surgery following a
      standardized protocol to move from a mandibular smile to a voluntary, then
      spontaneous, smile in three steps. The LTM is the main part of a one-stage global
      treatment of the paralyzed face. It constitutes a dynamic palliative treatment
      usually started at the sequelae stage, 18 month after the outcome of a peripheral
      facial paralysis. This one-stage procedure is a reproducible and relevant
      surgical technique in the difficult treatment of peripheral facial paralysis. It
      allows implementing an active muscle transfer to reanimate the labial commissure
      and re-create a mobile nasolabial fold. 

PMID- 25958898
TI  - Cross-facial nerve grafting for facial reanimation.
AB  - Dynamic facial reanimation is the gold standard treatment for a paralyzed face.
      Over the last century, multiple nerves have been utilized for grafting to the
      facial nerve in an attempt to produce improved movement. However, in recent
      years, the use of cross facial nerve grafting with a second stage gracilis free
      flap has gained popularity due to the ability to generate a spontaneous smile and
      facial movement. Preoperative history taking and careful examination, as well as
      pre-surgical planning, are imperative to whether cross facial nerve grafting with
      a second stage gracilis free flap is appropriate for the patient. A sural nerve
      graft is ideal given the accessibility of the nerve, the length, as well as the
      reliability and ease of the nerve harvest. The nerve can be harvested using a
      small incision, which leaves the patient with minimal post operative morbidity.
      In this chapter, we highlight the pearls and pitfalls of cross facial nerve
      grafting. 

PMID- 25958900
TI  - Management of the eye in facial paralysis.
AB  - Facial nerve palsy, whether the cause is idiopathic, or following such insults as
      surgery, trauma, or malignancy, places the health of the ocular surface at risk.
      Reduced or absent orbicularis oculi function results in lagophthalmos and
      exposure of the cornea, which is exacerbated by eyelid malposition. Management of
      the exposure keratopathy is paramount to prevent corneal breakdown, scarring, and
      permanent vision loss. Significant exposure keratopathy can be complicated by
      loss of corneal sensation, leading to a neurotrophic corneal ulcer. Initial
      management consists of artificial tear drops and ointment for corneal lubrication
      and strategies to address the lagophthalmos. Once the condition of the ocular
      surface has been stabilized, a variety of surgical treatment options are
      available depending on the severity and persistence of eyelid and ocular
      findings. The most common surgical options include temporary or permanent
      tarsorrhaphy for lagophthalmos, upper eyelid weight placement for retraction, and
      lateral canthoplasty with or without a middle lamellar spacer for lower eyelid
      retraction. External eyelid loading is a good option in patients who are poor
      surgical candidates or who have a known temporary palsy of short duration. The
      goal of all such procedures must be protection of the ocular surface through
      optimization of eyelid position. 

PMID- 25958899
TI  - Gracilis microneurovascular transfer for facial paralysis.
AB  - Facial nerve dysfunction occurs in varying degrees of severity due to several
      causes, and leads to asymmetric or absent facial movements. Regardless of the
      etiology, facial nerve dysfunction can be functionally and psychologically
      devastating. Many techniques to restore facial symmetry both at rest and with
      motion have been pursued throughout history. Within the past 30 years, free
      muscle microneurovascular transfer techniques have been developed to provide
      symmetric motion to the face. The aim of this article is to describe one of the
      most common and reliable techniques to restore midface mobility, namely, gracilis
      microneurovascular transfer. 

PMID- 25958901
TI  - Dynamic muscle transfer in facial nerve palsy: the use of contralateral
      orbicularis oculi muscle.
AB  - The aim of the study is to describe the results of dynamic muscle transfer with
      an orbicularis oculi muscle flap from the contralateral side to the paralyzed
      side in patients with House-Brackmann grade 6 facial nerve palsy. This case
      series included six patients who underwent dynamic muscle transfer with a flap of
      healthy orbicularis oculi muscle fibers from the contralateral side into the
      paralyzed orbicularis oculi muscle. All patients had a House-Brackmann grade 6
      facial nerve palsy. They all had previous multiple surgical procedures to improve
      the eyelid function. In spite of this, they were all symptomatic in terms of
      corneal exposure before orbicularis muscle transfer. All patients had
      postoperative follow up in excess of 2 years after the procedure. All patients
      improved symptomatically and had clinically reduced lagophthalmos
      postoperatively. Five patients who had an absent blink reflex showed a
      significant improvement in their blink reflex postoperatively. No complications
      occurred at the donor site. All patients showed a significant improvement of
      their symptoms and their lagophthalmos reduced postoperatively. Most importantly,
      the blink occurred involuntarily at the same time as the blink on the normal
      side. The authors propose that a dynamic muscle transfer using the contralateral
      orbicularis muscle may be considered to improve the voluntary lid closure and
      spontaneous blink reflex to improve corneal exposure in patients with grade 6
      facial palsy who have not benefited from conventional surgical procedures. 

PMID- 25958902
TI  - Dynamic change of myogenin in denervated rat mimetic muscle.
AB  - We previously reported double innervation of rat mimetic muscles with labeling of
      facial nuclei. However, whether denervated mimetic muscles are affected after
      such nerve repair is not known. Rats were divided into five groups: Group A,
      controls; Group B, complete facial palsy; Group C, complete facial palsy with
      repair using end-to-end neurorrhaphy; Group D, incomplete facial palsy; and Group
      E, incomplete facial palsy with repair using end-to-side neurorrhaphy.
      Preoperatively and postoperatively, facial palsy and myogenin (Myog) expression
      in mimetic muscles were evaluated. Expression peaked on day 7 in Group B but was
      lower in Groups C and D. Expression in Groups D and E was comparable on day 28,
      and each model's score showed characteristic changes. Myog expression in facial
      mimetic muscles increases with denervation and decreases with nerve repair.
      Determining Myog expression levels in mimetic muscles just after nerve repair may
      help surgeons predict postoperative prognosis in facial palsy. 

PMID- 25958903
TI  - Comparison of face types in Chinese women using three-dimensional computed
      tomography.
AB  - This study compared inverted triangle and square faces of 21 young Chinese Han
      women (18-25 years old) using three-dimensional computed tomography images
      retrieved from a records database. In this study, 11 patients had inverted
      triangle faces and 10 had square faces. The anatomic features were examined and
      compared. There were significant differences in lower face width, lower face
      height, masseter thickness, middle/lower face width ratio, and lower face
      width/height ratio between the two facial types (p < 0.01). Lower face width was
      positively correlated with masseter thickness and negatively correlated with
      gonial angle. Lower face height was positively correlated with gonial angle and
      negatively correlated with masseter thickness, and gonial angle was negatively
      correlated with masseter thickness. In young Chinese Han women, inverted triangle
      faces and square faces differ significantly in masseter thickness and lower face
      height. 

PMID- 25958904
TI  - Diced and crushed cartilage plus autologous fibrin matrix obtained by a simple
      process for dorsal augmentation of the Mestizo nose.
AB  - Several alternatives can be used for nasal dorsum augmentation. We report the use
      of crushed diced cartilage embedded in an autologous fibrin matrix. This
      construct is placed on the nasal dorsum and is gently molded according to the
      characteristics of each patient. Rhinoplasty and nasal dorsum augmentation were
      performed in 45 patients with Mestizo characteristics after a complete medical
      history and development of a surgical plan. A crushed diced cartilage autologous
      graft and an autologous fibrin matrix from peripheral blood processed using the
      Choukroun method was used. Pre- and postoperative photographs were taken at short
      and long-term follow-up. Two separate variables were evaluated: reabsorption and
      irregularities. Three plastic surgeons evaluated the results, using a Likert
      scale: the first variable was considered very excellent in 88.9%, very good in
      6.7%, good in 4.4% with no poor or very poor results. In the second variable,
      results were excellent in 88.9%, very good in 4.4%, good in 3.4%, and poor in
      3.3% with no very poor results. Our patients carry a volume with an aesthetically
      pleasing contour and form with no changes over a mean follow-up period of 4
      years. Long-term effectiveness continues to be the main topic of discussion;
      however, this method can be considered an alternative not only to augment but
      also to smoothen irregularities of the nasal dorsum. We used a simple method with
      good and stable long-term clinical results. 

PMID- 25958905
TI  - The changes in histopathology and mass in hyperbaric oxygen-treated auricular
      cartilage grafts in a rabbit model.
AB  - The aim of the study is to investigate the histopathologic and cartilage mass
      changes in hyperbaric oxygen (HBO)-treated auricular cartilage grafts either
      crushed or fascia wrapped in a rabbit model. This is a prospective, controlled
      experimental study. Sixteen rabbits were randomly allocated into control (n = 8)
      and treatment groups (n = 8). Each group was further grouped as crushed cartilage
      (n = 4) and fascia wrapped crushed cartilage (n = 4). The eight rabbits in the
      treatment group had HBO once daily for 10 days as total of 10 sessions. The mass
      of cartilage, cartilage edge layout, structural layout, staining disorders of the
      chondroid matrix, necrosis, calcification besides bone metaplasia, chronic
      inflammation in the surrounding tissues, fibrosis, and increased vascularity were
      evaluated in the hematoxylin and eosin (H&E)-stained sections. Fibrosis in the
      surrounding tissue and cartilage matrix was evaluated with Masson's trichrome
      stain. The toluidine blue staining was used to evaluate loss of metachromasia in
      matrix. The prevalence of glial fibrillary acidic protein (GFAP) staining in
      chondrocytes was also evaluated. Although the remaining amount of cartilage mass
      after implantation does not show a significant difference between the control and
      the study group (p = 0.322, p <0.05).The difference between control and study
      group in terms of positive staining with GFAP was statistically significant (p =
      0.01, p <0.05). Necrosis and loss of matrix metachromasia were significantly low
      in the study group compared with control group (p = 0.001, p = 0.006, p <0.05).
      HBO therapy did not have significant effect on the mass of rabbit auricular
      cartilage graft. HBO therapy significantly reduced loss of metachromasia,
      necrosis, and GFAP staining in the auricular cartilage grafts of the animal
      model. 

PMID- 25958906
TI  - Effects of feeding different levels of corn steep liquor on the performance of
      fattening lambs.
AB  - This study was conducted to assess the effect of feeding corn steep liquor (CSL)
      on in vivo digestibility, ruminal pH, ammonia and hydrolytic enzyme activities,
      blood metabolites, feed intake (FI) and growth performance in fattening lambs.
      The CSL is a by-product of wet milling process of maize starch industry. The
      crude protein (CP), rumen-degradable protein (RDP), lactic acid and metabolisable
      energy contents of this by-product were 420, 324, 200 g/kg dry matter (DM) and
      12.6 MJ/kg DM respectively. Twenty-seven male Moghani lambs were assigned
      randomly into three groups of nine lambs each in a completely randomised design.
      Three iso-energetic and iso-nitrogenous diets containing different levels (0, 50
      or 100 g/kg dry matter) of CSL were offered ad libitum three times a day. Forage
      to concentrate ratio of the diets was 30:70. With inclusion of CSL in diet, the
      contents of canola meal, fish meal, wheat bran, corn grain and sugar beet pulp
      were decreased. The contents of DM, ash-free neutral detergent fibre (NDFom),
      ether extract, starch, Ca and S were numerically lower, but soluble protein, RDP
      and non-fibre carbohydrates were greater in the diets containing CSL in
      comparison with the control diet. The lambs fed with the diets containing CSL had
      lower [linear (L), p < 0.06] digestibility coefficients of DM and NDFom as
      compared to those fed with the diet free of CSL. Ruminal ammonia-N concentration
      increased (L, p < 0.05), but pH decreased (L, p < 0.05) with raising CSL level in
      diet. Carboxymethyl cellulase and filter paper-degrading activities decreased (L,
      p < 0.05), while proteases activity increased (L, p < 0.05) as dietary rates of
      CSL increased. Microcrystalline cellulase and alpha-amylase activities were
      similar among the treatments. Within blood metabolites, only urea-N concentration
      increased (L, p < 0.05) in the lambs receiving CSL as compared to those fed with
      diet without CSL. Dietary inclusion of CSL resulted in linear decreases (L, p <
      0.05) in the intakes of DM, organic matter, CP, NDFom and ash-free acid detergent
      fibre, and average daily gain. However, the feed conversion ratio was similar
      among the experimental animals. Overall, feeding CSL up to 100 g/kg diet DM in
      lamb resulted in reductions of rumen fibrolytic microbial enzyme activities, in
      vivo digestibility, FI and growth performance, but rumen proteases activity
      increased.

PMID- 25958907
TI  - The prevalence of metabolic syndrome among low-income South Asian Americans.
AB  - OBJECTIVE: The purpose of the present paper is to examine the prevalence of
      metabolic syndrome (MetS) and its components using the harmonized definition in
      an interviewed sub-sample of diverse, low-income, adult South Asians (SA) of both
      sexes residing in Maryland. We also wanted to derive a BMI cut-off value that was
      highly correlated with the recommended waist circumference (WC) that we could
      apply to a larger sample of SA Americans for whom only BMI values were available
      from clinic files. We also examined differences in MetS prevalence among various
      Asian ethnic groups (defined by country of origin) and the clustering pattern of
      their MetS components. DESIGN: Clinical data extraction on subjects (n 1002) and
      interviewees (n 401) were used in a cross-sectional study of SA Americans.
      SETTING: Two community health centres in Montgomery and Baltimore County, MD,
      USA. SUBJECTS: SA adult males and females (n 1403) aged 20-68 years. RESULTS: The
      prevalence of MetS using harmonized WC cut-offs (90 cm in men and 80 cm in women)
      was 47% in men and 54% in women. Using a BMI of 23.0 kg/m2 gave a similar
      prevalence of MetS for males (48%) and females (47%). Of the five MetS
      components, the prevalence pattern differed among the ethnic groups, particularly
      for SA Indians. CONCLUSIONS: The prevalence of MetS in a diverse, low-income, SA
      American immigrant group using the harmonized definition was 51%. Derived lowered
      BMI cut-off of 23.0 kg/m2 should be used by clinicians in studies on SA when WC
      values are not available for detecting metabolic risk. SA Indians had a higher
      prevalence of abnormal TAG and blood glucose values compared with other SA, and
      therefore results for SA Indians should not be generalized to all SA ethnic
      groups.

PMID- 25958908
TI  - [Kamikihito improves memory dysfunction in Alzheimer's disease].

PMID- 25958909
TI  - [Pharmacological superiority of nobiletin-rich Citrus reticulata peel, a
      multicomponent drug, over nobiletin alone regarding anti-dementia action].

PMID- 25958910
TI  - [Clinical effects of the NChinpi on the cognitive impairment of patients with
      Alzheimer's disease].

PMID- 25958911
TI  - [Mechanisms of prostaglandin actions in the nervous system].

PMID- 25958912
TI  - [New drugs from Japan will be created from the nation-wide open style innovation
      network].

PMID- 25958913
TI  - [Pharmacological characteristics and clinical results of efinaconazole
      (Clenafin(r) Topical Solution 10%), a novel anti-onychomycosis drug].

PMID- 25958914
TI  - [Pharmacological properties of abiraterone acetate (ZYTIGA(r) tablet 250 mg), a
      new drug for the treatment of castration-resistant prostate cancer, and results
      of its clinical studies].

PMID- 25958915
TI  - [PET imaging of alpha7 nicotinic receptor].

PMID- 25958916
TI  - [PET imaging of tau lesions].

PMID- 25958917
TI  - [Verification of Williams multiple comparison in unbalanced data].

PMID- 25958918
TI  - Development of a gas-cylinder-free plasma desorption/ionization system for on
      site detection of chemical warfare agents.
AB  - A gas-cylinder-free plasma desorption/ionization system was developed to realize
      a mobile on-site analytical device for detection of chemical warfare agents
      (CWAs). In this system, the plasma source was directly connected to the inlet of
      a mass spectrometer. The plasma can be generated with ambient air, which is drawn
      into the discharge region by negative pressure in the mass spectrometer. High
      power density pulsed plasma of 100 kW could be generated by using a microhollow
      cathode and a laboratory-built high-intensity pulsed power supply (pulse width:
      10-20 MUs; repetition frequency: 50 Hz). CWAs were desorbed and protonated in the
      enclosed space adjacent to the plasma source. Protonated sample molecules were
      introduced to the mass spectrometer by airflow through the discharge region. To
      evaluate the analytical performance of this device, helium and air plasma were
      directly irradiated to CWAs in the gas-cylinder-free plasma desorption/ionization
      system and the protonated molecules were analyzed by using an ion-trap mass
      spectrometer. A blister agent (nitrogen mustard 3) and nerve gases
      [cyclohexylsarin (GF), tabun (GA), and O-ethyl S-2-N,N-diisopropylaminoethyl
      methylphosphonothiolate (VX)] in solution in n-hexane were applied to the Teflon
      rod and used as test samples, after solvent evaporation. As a result, protonated
      molecules of CWAs were successfully observed as the characteristic ion peaks at
      m/z 204, 181, 163, and 268, respectively. In air plasma, the limits of detection
      were estimated to be 22, 20, 4.8, and 1.0 pmol, respectively, which were lower
      than those obtained with helium plasma. To achieve quantitative analysis,
      calibration curves were made by using CWA stimulant dipinacolyl methylphosphonate
      as an internal standard; straight correlation lines (R(2) = 0.9998) of the peak
      intensity ratios (target per internal standard) were obtained. Remarkably, GA and
      GF gave protonated dimer ions, and the ratios of the protonated dimer ions to the
      protonated monomers increased with the amount of GA and GF applied. 

PMID- 25958919
TI  - Patients with psoriasis are at a higher risk of developing nonalcoholic fatty
      liver disease.
AB  - BACKGROUND: Psoriasis is a chronic, immune-mediated inflammatory skin disease
      with many extracutaneous manifestations. Several recent studies have indicated an
      increased prevalence of nonalcoholic fatty liver disease (NAFLD) among patients
      with psoriasis. In the present study, we investigated the prevalence of NAFLD in
      a population of Iranian patients with psoriasis. METHODS: NAFLD was assessed and
      graded using ultrasonography in 123 patients with psoriasis and 123 healthy
      controls (HCs) matched by age, sex and body mass index (BMI). RESULTS: The
      prevalence of NAFLD was significantly higher in the psoriatic group compared with
      the HC group (65.6% vs. 35%, P < 0.01, OR = 3.53). Median NAFLD grade was
      significantly greater in patients with psoriasis compared with HCs (grade 2 vs.
      grade 1, P < 0.01). In patients with psoriasis, NAFLD was associated with a
      higher frequency of hypertension (16.5%), abnormal liver function test (LFT)
      results (16.4%) and metabolic syndrome (46.6%). Moreover, patients with psoriasis
      and NAFLD tended to have significantly higher values for BMI, waist circumference
      (WC), Psoriasis Activity and Severity Index (PASI), and levels of serum
      triglyceride, cholesterol, low-density lipoprotein and fasting blood sugar (FBS).
      Multivariate logistic regression revealed that WC, PASI, LFT abnormalities,
      hypertension and cigarette smoking were independent predictors of NAFLD grade.
      CONCLUSIONS: Our findings warrant a detailed assessment of metabolic
      comorbidities including NAFLD in patients with a primary diagnosis of psoriasis.
      Lifestyle modifications, including weight loss and smoking cessation, may be
      necessary for patients with psoriasis to decrease the risk and severity of NAFLD.

PMID- 25958920
TI  - Exposure to soil, house dust and decaying plants increases gut microbial
      diversity and decreases serum immunoglobulin E levels in BALB/c mice.
AB  - To assess the impact of sanitation of a living environment on gut microbiota and
      development of the immune system, we raised BALB/c mice under three distinct
      environmental conditions: a specific pathogen-free animal room (SPF), a general
      animal room (XZ) and a farmhouse (JD). All other variables like diet, age,
      genetic background, physiological status and original gut microbiota were
      controlled for in the three groups. Using high-throughput sequencing of the 16S
      rRNA gene, we found that each mouse group had a specific structure of the gut
      microbial community. Groups JD and XZ harboured a significantly more diverse and
      richer gut microbiota than did group SPF. Bacteroidetes were significantly more
      abundant in groups XZ and JD than in group SPF, whereas Firmicutes showed the
      inverse pattern. Total serum immunoglobulin E (IgE) levels were significantly
      lower in groups XZ and JD than in group SPF. There were no significant
      differences in gut microbiota diversity and serum IgE concentration between
      groups JD and XZ, but we found higher abundance of dominant genera in the gut
      microflora of group JD. We conclude that exposure to soil, house dust and
      decaying plant material enhances gut microbial diversity and innate immunity. Our
      results seem to provide new evidence supporting the hygiene hypothesis.

PMID- 25958921
TI  - Estrogen as a new option for prevention and treatment of breast cancer - does
      this need a 'time gap'?
AB  - Due to experimental and clinical data, the hypothesis has been raised that a
      'time gap' is necessary to achieve 'carcinoprotection' by estrogen therapy in
      postmenopausal women, possibly also in combination with certain ('neutral')
      progestogens. As the mechanism, apoptotic effects are discussed, which, however,
      would only work after long-term estrogen deprivation. Based on this hypothesis,
      in general, an early initiation of menopausal hormone therapy would increase the
      risk of breast cancer, in sharp contrast to the beneficial cardiovascular
      effects, only protective within the 'window of opportunity' directly after
      menopause. However, other mechanisms are possible which could work without a time
      gap, leading to a decreased risk of breast cancer or even being carcinoprotective
      compared with no treatment. For example, within estradiol metabolism,
      carcinoprotective enzymes can be upregulated and protective estradiol metabolites
      can be produced, as shown, for example, especially in women with balanced
      nutrition and physical activity. In addition, it has to be considered that a long
      time is needed to see any clinical effects based on the biological mechanisms
      which may start early after estrogen exposure. Thus, more research and studies
      are needed to prove the 'gap hypothesis', and it may be that estrogen is
      beneficial for a woman at any time of her life. 

PMID- 25958923
TI  - Nonparametric directionality measures for time series and point process data.
AB  - The need to determine the directionality of interactions between neural signals
      is a key requirement for analysis of multichannel recordings. Approaches most
      commonly used are parametric, typically relying on autoregressive models. A
      number of concerns have been expressed regarding parametric approaches, thus
      there is a need to consider alternatives. We present an alternative nonparametric
      approach for construction of directionality measures for bivariate random
      processes. The method combines time and frequency domain representations of
      bivariate data to decompose the correlation by direction. Our framework generates
      two sets of complementary measures, a set of scalar measures, which decompose the
      total product moment correlation coefficient summatively into three terms by
      direction and a set of functions which decompose the coherence summatively at
      each frequency into three terms by direction: forward direction, reverse
      direction and instantaneous interaction. It can be undertaken as an addition to a
      standard bivariate spectral and coherence analysis, and applied to either time
      series or point-process (spike train) data or mixtures of the two (hybrid data).
      In this paper, we demonstrate application to spike train data using simulated
      cortical neurone networks and application to experimental data from isolated
      muscle spindle sensory endings subject to random efferent stimulation. 

PMID- 25958922
TI  - Speciation dynamics during the global radiation of extant bats.
AB  - Species richness varies widely across extant clades, but the causes of this
      variation remain poorly understood. We investigate the role of diversification
      rate heterogeneity in shaping patterns of diversity across families of extant
      bats. To provide a robust framework for macroevolutionary inference, we assemble
      a time-calibrated, species-level phylogeny using a supermatrix of mitochondrial
      and nuclear sequence data. We analyze the phylogeny using a Bayesian method for
      modeling complex evolutionary dynamics. Surprisingly, we find that variation in
      family richness can largely be explained without invoking heterogeneous
      diversification dynamics. We document only a single well-supported shift in
      diversification dynamics across bats, occurring at the base of the subfamily
      Stenodermatinae. Bat diversity is phylogenetically imbalanced, but-contrary to
      previous hypotheses-this pattern is unexplained by any simple patterns of
      diversification rate heterogeneity. This discordance may indicate that
      diversification dynamics are more complex than can be captured using the
      statistical tools available for modeling data at this scale. We infer that bats
      as a whole are almost entirely united into one macroevolutionary cohort, with
      decelerating speciation through time. There is also a significant relationship
      between clade age and richness, suggesting that global bat diversity may still be
      expanding. 

PMID- 25958924
TI  - West Nile Virus Surveillance in the Lombardy Region, Northern Italy.
AB  - In 2013, the circulation of West Nile virus (WNV) was detected in the Lombardy
      region and the following year a surveillance programme was activated with the aim
      of early identification of the viral distribution in mosquitoes and wild birds. A
      total of 50 959 Culex spp. mosquitoes grouped in six hundred and forty-seven
      pools as well as 1400 birds were screened by RT-PCR for the presence of West Nile
      virus leading to the identification of the viral genome in 32 mosquito pools and
      13 wild birds. The surveillance was able to detect the WNV circulation on an
      average of 42 days (CI 95% 29.98-53.86; Student's t-distribution) before the
      occurrence of human West Nile disease (WND) cases in the same area. These results
      demonstrate the presence of WNV in the Lombardy region and confirm entomological
      and wild birds surveillance as an effective measure for the early identification
      of WNV circulation in infected areas, thus providing a useful and cost-effective
      tool for the public health authorities in the application of measures to prevent
      human infection.

PMID- 25958925
TI  - Carprofen pharmacokinetics in plasma and in control and inflamed canine tissue
      fluid using in vivo ultrafiltration.
AB  - Measurement of unbound drug concentrations at their sites of action is necessary
      for accurate PK/PD modeling. The objective of this study was to determine the
      unbound concentration of carprofen in canine interstitial fluid (ISF) using in
      vivo ultrafiltration and to compare pharmacokinetic parameters of free carprofen
      concentrations between inflamed and control tissue sites. We hypothesized that
      active concentrations of carprofen would exhibit different dispositions in ISF
      between inflamed vs. normal tissues. Bilateral ultrafiltration probes were placed
      subcutaneously in six healthy Beagle dogs 12 h prior to induction of
      inflammation. Two milliliters of either 2% carrageenan or saline control was
      injected subcutaneously at each probe site, 12 h prior to intravenous carprofen
      (4 mg/kg) administration. Plasma and ISF samples were collected at regular
      intervals for 72 h, and carprofen concentrations were determined using HPLC.
      Prostaglandin E2 (PGE2 ) concentrations were quantified in ISF using ELISA.
      Unbound carprofen concentrations were higher in ISF compared with predicted
      unbound plasma drug concentrations. Concentrations were not significantly higher
      in inflamed ISF compared with control ISF. Compartmental modeling was used to
      generate pharmacokinetic parameter estimates, which were not significantly
      different between sites. Terminal half-life (T1/2) was longer in the ISF compared
      with plasma. PGE2 in ISF decreased following administration of carprofen. In vivo
      ultrafiltration is a reliable method to determine unbound carprofen in ISF, and
      that disposition of unbound drug into tissue is much higher than predicted from
      unbound drug concentration in plasma. However, concentrations and pharmacokinetic
      parameter estimates are not significantly different in inflamed vs. un-inflamed
      tissues.

PMID- 25958926
TI  - Vosaroxin is a novel topoisomerase-II inhibitor with efficacy in relapsed and
      refractory acute myeloid leukaemia.
AB  - INTRODUCTION: Vosaroxin is a first-in-class anti-cancer quinolone that inhibits
      topoisomerase-II leading to cell cycle arrest and apoptosis. It has shown
      efficacy in a range of solid organ and haematopoietic tumours in vitro, and
      several clinical trials are underway or completed in the field of Acute Myeloid
      Leukaemia (AML). The treatment of relapsed and refractory AML is a clinical
      challenge, where long-term survival is rare without allogeneic haematopoietic
      stem cell transplantation. AREAS COVERED: We review the data from the published
      clinical trials of vosaroxin, including the recently presented Phase III VALOR
      study. In combination with intermediate dose cytarabine, vosaroxin almost doubled
      complete response (CR) rates in relapsed and refractory AML compared with
      cytarabine alone, and prolonged median survival by 1.4 months. EXPERT OPINION:
      Vosaroxin is a promising new agent in the treatment of AML, with the potential to
      improve CR rates in a high-risk group of patients with relapsed and refractory
      AML. However, higher CR rates have been associated with higher rates of treatment
      related morbidity and mortality, especially in elderly/unfit patients. Maximising
      the potential of vosaroxin will therefore require the identification of patients
      most likely to benefit from vosaroxin-containing combination regimens.

PMID- 25958927
TI  - The effects of mycophenolate mofetil on cytokines and their receptors in
      pulmonary arterial hypertension in rats.
AB  - OBJECTIVES: To analyse the effects of mycophenolate mofetil (MMF) on pulmonary
      artery pressure (PAP) and the expression of cytokines and their receptors in a
      rat model of pulmonary arterial hypertension (PAH). METHOD: Thirty-eight healthy
      male inbred Sprague-Dawley rats were divided randomly into four groups: a control
      group, a monocrotaline (MCT) group, an MMF20 group (MCT+20 mg/kg/day MMF), and an
      MMF40 group (MCT+40 mg/kg/day MMF). Systolic PAP (SPAP), the right ventricular
      hypertrophy index (RVI), and the levels of expression of cytokines and their
      receptors were measured and analysed. RESULTS: SPAP, RVI, levels of expression of
      basic fibroblast growth factor (bFGF) in serum and lung homogenates, alveolar
      arterial wall thickness, and the number of muscular arteries in the MMF20 and
      MMF40 groups were decreased in comparison with the MCT group. CONCLUSIONS: MMF
      inhibits the formation of vascular muscle and decreases SPAP and RVI by
      inhibition of the expression of bFGF, endothelin-1 (ET-1), and their receptors,
      resulting in the inhibition of smooth muscle proliferation and amelioration of
      PAH.

PMID- 25958928
TI  - Melatonin inhibits autophagy and endoplasmic reticulum stress in mice with carbon
      tetrachloride-induced fibrosis.
AB  - This study aimed to investigate whether inhibition of autophagy and endoplasmic
      reticulum (ER stress) associates with the antifibrogenic effect of melatonin in
      mice treated with carbon tetrachloride (CCl4 ). Mice received CCl4 5 MUL/g body
      wt i.p. twice a week for 4 wk or 6 wk. Melatonin was given at 5 or 10 mg/kg/day
      i.p, beginning 2 wk after the start of CCl4 administration. Treatment with CCl4
      resulted in fibrosis evidenced by the staining of alpha-smooth muscle actin
      (alpha-SMA)-positive cells. CCl4 induced an autophagic response measured as the
      presence of autophagic vesicles, protein 1 light chain 3 (LC3) staining,
      conversion of LC3-I to autophagosome-associated LC3-II, changes in expression of
      beclin-1, UV radiation resistance-associated gene (UVRAG), ubiquitin-like
      autophagy-related (Atg5), Atg12, Atg16L1, sequestosome 1 (p62/SQSTM1), and
      lysosome-associated membrane protein (LAMP)-2, and increased phosphorylation of
      the mammalian target of rapamycin (mTOR). There was an increase in the expression
      of the ER stress chaperones CCAAT/enhancer-binding protein homologous protein
      (CHOP), immunoglobulin-heavy-chain-binding protein (BiP/GRP78), and 94-kDa
      glucose-regulated protein (GRP94), and in the mRNA levels of pancreatic ER kinase
      (PERK), activating transcription factor 6 (ATF6), ATF4, inositol-requiring enzyme
      1 (IRE1), and spliced X-box-binding protein-1 (XBP1). Phospho-IRE1, ATF6, and
      phospho-PERK protein concentration also increased significantly.
      Immunohistochemical staining of alpha-SMA indicated an abrogation of hepatic
      stellate cells activation by melatonin. Furthermore, treatment with the indole
      resulted in significant inhibition of the autophagic flux and the unfolded
      protein response. Findings from this study give new insight into molecular
      pathways accounting for the protective effect of melatonin in fibrogenesis.

PMID- 25958929
TI  - Aleukemic solitary cutaneous myeloid sarcoma.

PMID- 25958930
TI  - Variants on Chromosome 9p21 Confer Risks of Noncardioembolic Cerebral Infarction
      and Carotid Plaque in the Chinese Han Population.
AB  - AIMS: Considering that cerebral infarction (CI) may share a common etiological
      basis with coronary artery disease (CAD), we evaluated six CAD-related single
      nucleotide polymorphisms (SNPs) on 9p21 for investigating the effect of 9p21 on
      CI or carotid plaque in the Chinese Han population. METHODS: Altogether, 528
      patients with noncardioembolic CI (375 with carotid plaque and 153 without
      carotid plaque) and 258 control subjects were genotyped. Six SNPs previously
      shown to be associated with CAD were sequenced and assessed for association with
      CI and carotid plaque using odds ratio (OR) and 95% confidence interval (CI) from
      logistic regression models. RESULTS: The G allele frequencies of rs2383206
      (OR=1.472, p=0.021) and rs4977574 (OR=1.519, p=0.013) significantly increased in
      patients with CI without carotid plaque compared with middle-aged patients in the
      control group. The CI risk was higher among the GG genotype carriers than among
      GA + AA genotype carriers (OR=1.794, 95% CI=1.059-3.039, p=0.030 for rs2383206;
      OR=1.866, 95% CI=1.088-3.201, p=0.023 for rs4977574). In comparison with the non
      GG genotype, the GG genotype of rs2383206 and rs4977574 combined had a 1.733-fold
      greater risk of CI in the middle-aged group. SNPs rs2383206 and rs4977574 were
      also associated with a risk of carotid plaque among patients with CI aged > 65
      years (OR=2.329, p=0.018 and OR=1.997, p=0.049, respectively). Moreover, six SNPs
      were strongly correlated with linkage disequilibrium. CONCLUSIONS: Genetic
      variations of rs2383206 and rs4977574 on 9p21 are potentially associated with CI
      and carotid plaque in the Chinese Han population. Our results provide further
      evidence that the 9p21 region represents a major risk locus for cerebrovascular
      diseases.

PMID- 25958931
TI  - Incidence and Expression of Circulating Cell Free p53-Related Genes in Acute
      Myocardial Infarction Patients.
AB  - AIM: The circulating RNA levels are predictive markers in several diseases. We
      determined the levels of circulating p53-related genes in patients with acute ST
      segment elevation myocardial infarction (STEMI), indicating major heart muscle
      damage. METHODS: Plasma RNA was extracted from the patients (n=45) upon their
      arrival to the hospital (STEMI 0h) and at four hours post-catheterization (STEMI
      4h) as well as from controls (n=34). RESULTS: Of 18 circulating p53-related
      genes, nine genes were detectable. A significantly lower incidence of circulating
      p21 (p < 0.0001), Notch1 (p=0.042) and BTG2 (p < 0.0001) was observed in the
      STEMI 0h samples in comparison to the STEMI 4h and control samples. Lower
      expression levels (2.1-fold) of circulating BNIP3L (p=0.011), p21 (3.4-fold,
      p=0.005) and BTG2 (6.3-fold, p=0.0001) were observed in the STEMI 0h samples in
      comparison to the STEMI 4h samples, with a 7.4-fold lower BTG2 expression (p <
      0.001) and 2.6-fold lower p21 expression (p=0.034) compared to the control
      samples. Moreover, the BNIP3L expression (borderline significance, p=0.0655)
      predicted the level of peak troponin, a marker of myocardial infarction. In
      addition, the BNIP3L levels on admission (p=0.0025), at post-catheterization
      (p=0.020) and the change between the groups (p=0.0079) were inversely associated
      with troponin. The BNIP3L (p=0.0139) and p21 levels (p=0.0447) were also
      associated with a longer time to catheterization. CONCLUSIONS: Our results
      suggest that circulating downstream targets of p53 are inhibited during severe
      AMI and subsequently re-expressed after catheterization, uncovering possible
      novel death-or-survival decisions regarding the fate of p53 in the heart and the
      potential use of its target genes as prognostic biomarkers for oxygenation
      normalization.

PMID- 25958932
TI  - Loci under selection during multiple range expansions of an invasive plant are
      mostly population specific, but patterns are associated with climate.
AB  - Identifying the genes underlying rapid evolutionary changes, describing their
      function and ascertaining the environmental pressures that determine fitness are
      the central elements needed for understanding of evolutionary processes and
      phenotypic changes that improve the fitness of populations. It has been
      hypothesized that rapid adaptive changes in new environments may contribute to
      the rapid spread and success of invasive plants and animals. As yet, studies of
      adaptation during invasion are scarce, as is knowledge of the genes underlying
      adaptation, especially in multiple replicated invasions. Here, we quantified how
      genotype frequencies change during invasions, resulting in rapid evolution of
      naturalized populations. We used six fully replicated common garden experiments
      in Brazil where Pinus taeda (loblolly pine) was introduced at the same time, in
      the same numbers, from the same seed sources, and has formed naturalized
      populations expanding outward from the plantations. We used a combination of
      nonparametric, population genetics and multivariate statistics to detect changes
      in genotype frequencies along each of the six naturalization gradients and their
      association with climate as well as shifts in allele frequencies compared to the
      source populations. Results show 25 genes with significant shifts in genotype
      frequencies. Six genes had shifts in more than one population. Climate explained
      25% of the variation in the groups of genes under selection across all locations,
      but specific genes under strong selection during invasions did not show climate
      related convergence. In conclusion, we detected rapid evolutionary changes during
      invasive range expansions, but the particular gene-level patterns of evolution
      may be population specific. 

PMID- 25958933
TI  - Clinical relevance of echocardiogram in patients with cerebral palsy undergoing
      posterior spinal fusion.
AB  - BACKGROUND: Spinal deformity is one of the secondary musculoskeletal problems
      that occur with cerebral palsy (CP). Of the co morbidities associated with CP and
      spinal deformity, cardiac function is of theoretical concern. OBJECTIVE: The goal
      of our study was to determine the clinical relevance of routine preoperative
      cardiology evaluation via echocardiogram for patients with CP presenting for
      posterior spine fusion (PSF) surgery. METHODS: A retrospective chart review was
      performed of CP patients presenting for scoliosis surgery. The data collected for
      each patient included: age, sex, height, weight, Cobb angle, and medical history.
      All patients had a preoperative cardiac evaluation. RESULTS: Seventy-two patients
      were included. The mean age was 13.6 +/- 3.4 years. Left ventricular systolic
      function was normal in all patients; the mean shortening fraction was 39.3 +/-
      6.2%. No patient had more than mild insufficiency of either the semilunar or
      atrioventricular valve. One patient was diagnosed with aortic root dilation as
      well as aortic valve insufficiency. All patients had PSF surgery without changes
      in anesthetic or surgical plans, and no patient experienced complications
      attributable to a cardiac origin. CONCLUSION: The results suggest that routine
      preoperative cardiology evaluation via echocardiogram for children with CP in the
      absence of clinical history or physical examination findings suggestive of
      cardiac disease is not necessary.

PMID- 25958934
TI  - Impact of dietary plane of energy during the dry period on lipoprotein parameters
      in the transition period in dairy cattle.
AB  - The high energy demands of dairy cows during the transition period from late
      gestation into early lactation can place them at an increased risk for the
      development of metabolic and infectious diseases. Modification of the dry period
      diet has been investigated as a preventive means to minimize the detrimental
      aspects of metabolic shifts during the transition period. Studies investigating
      the impact of dry period diet on lipid parameters during the transition period
      have largely focused on markers of lipolysis and ketogenesis. Total cholesterol
      declines during the periparturient period and increases in early lactation. The
      impact total energy in the dry period diet has on the ability of the cow to
      maintain total serum cholesterol, as well as its natural high-density lipoprotein
      rich status, during this metabolically challenging window is not clear. The
      impact of lipoproteins on inflammation and immune function may have a clinical
      impact on the cow's ability to ward off production-related diseases. In this
      study, we hypothesized that the provision of adequate, but not excessive, total
      metabolizable energy, would better allow the cow to maintain total cholesterol
      and a higher relative proportion of HDL throughout the transition period. Cows
      were allocated to one of three dry period dietary treatment groups following a
      randomized block design. Total serum triglycerides, cholesterol and lipoprotein
      fractions were measured on a weekly basis from approximately 7 weeks pre-calving
      to 6 weeks post-calving. The cows on the high energy diet maintained total serum
      cholesterol as compared to the cows provided a lower energy diet, but there was
      no significant increase in the LDL fraction of lipoproteins between diet
      treatment groups.

PMID- 25958935
TI  - Female stickleback prefer shallow males: Sexual selection on nest microhabitat.
AB  - Sexual selection is most often thought of as acting on organismal traits, such as
      size or color. However, individuals' habitat use may also affect mating success.
      Here, we show that, in threespine stickleback, nest depth can be a target of
      sexual selection. In postglacial lakes in British Columbia, male threespine
      stickleback nest in a narrow range of depths. Prior studies revealed heritable
      variation in males' preferred nest microhabitat. We surveyed four natural
      populations, finding that male stickleback with shallower nests were more
      successful at breeding. Indeed, nest depth was a much stronger predictor of male
      mating success than more commonly studied targets of sexual selection in
      stickleback (size, condition, shape, color, infection status). This selection on
      nest depth means that variance in fitness changed predictably across
      microhabitats, altering the opportunity for sexual selection to act on other
      traits. Accordingly, we show that sexual selection on other male traits is
      strongest where variance in nesting success is highest (at intermediate nest
      depths in some lakes). We conclude that males' choice of nesting microhabitat is
      an especially important target of sexual selection, resulting in fine-scale
      spatial variation in sexual selection on other traits. 

PMID- 25958936
TI  - Relationship between sleep disturbance, depression and anxiety in the 12 months
      following a cardiac event.
AB  - We aimed to assess the prevalence of sleep disturbance in a cardiac patient
      population over a 12-month period and assess its relationship with treatment
      adherence, self-efficacy, anxiety and depression. A total of 134 patients
      consecutively admitted to two Australian hospitals after acute myocardial
      infarction (31%), or to undergo bypass surgery (29%) or percutaneous coronary
      intervention (40%) were interviewed at six weeks and four and 12 months. Sleep
      disturbance was measured using a recode of the Beck Depression Inventory (v.2)
      item 16. Anxiety and depression were assessed by the Hospital Anxiety and
      Depression Scale. Sleep disturbance was highly prevalent (69%) at 6 weeks but was
      not associated with 12-month psychological outcomes. Path analysis revealed that
      sleep disturbance at 4 months was, however, associated with reduced treatment
      adherence and self-efficacy, and higher anxiety and depression scores at 12
      months. The high prevalence of sleep disturbance in this study and its
      association with psychological outcomes may have adverse prognostic implications
      and possibly impede cardiac rehabilitation efforts.

PMID- 25958937
TI  - Incidence and Risk Factors for Upper Extremity Climbing Injuries in Indoor
      Climbers.
AB  - The purpose of this study was to describe the prevalence, incidence and risk
      factors for climbing-related injuries of the upper extremities in recreational
      climbers. A total of 426 recreational climbers were recruited from indoor
      climbing halls. The baseline questionnaire included questions on potential risk
      factors for climbing injuries: personal factors, climbing-related factors and
      upper extremity injuries that had occurred in the previous 12 months. Follow-up
      questionnaires collected information on new injuries that occurred during the
      follow-up period. The incidence of climbing-related injuries during one-year
      follow-up was 42.4% with 13 injuries per 1000 h of climbing. The finger was the
      most frequently affected injury location (36.0%). The following risk factors were
      associated with the occurrence of upper extremity injuries: higher age (OR 1.03,
      95% CI 1.01;1.05), performing a cooling-down (OR 2.02, 95% CI 1.28;3.18),
      climbing with campus board (OR 2.48, 95% CI 1.23;5.02), finger strength middle
      finger (OR 1.12, 95% CI 1.05;1.18) and previous injuries (OR 3.05, 95% CI
      2.01;4.83). Climbing injuries of the upper body extremities are very common among
      recreational climbers in indoor halls and several risk factors can be identified
      that are related to a higher injury risk.

PMID- 25958938
TI  - Effects of Swimming on the Inflammatory and Redox Response in a Model of Allergic
      Asthma.

PMID- 25958939
TI  - Letter to the Editor.

PMID- 25958940
TI  - Importance of Peak Height Velocity Timing in Terms of Injuries in Talented Soccer
      Players.

PMID- 25958941
TI  - Carbohydrate Management in Athletes with Type 1 Diabetes in a 10 km Run
      Competition.
AB  - The aim of this study was to identify the real consumption of CHO during a 10 km
      competitive run, to compare data with the recommended quantities according to
      current guidelines, and to analyse the clinical events associated with these
      different amounts. Protocol 1: observational study including 31 athletes with T1D
      and 127 athletes without diabetes, comparing data taken from dietary records of
      CHO intake on the competition day. Protocol 2: single-blind randomized trial in
      18 athletes with T1D, testing a pre-exercise CHO supplement of 0.7 g CHO.kg(- 1)
      (n=10) or 0.35 g CHO.kg(- 1) (n=8). The results showed that T1D athletes consumed
      a lower quantity of CHO than athletes without diabetes at their usual breakfast
      and during the meal taken<1 h after the competition, but no differences were
      found in the supplement taken before the competition. In the randomized study,
      athletes consuming the higher dose of CHO (0.7 g CHO.kg(- 1)) showed increased
      glycemic levels, comparing with the lower dose (0.35 g CHO.kg(- 1)). In
      conclusion, athletes with T1D seem to increase CHO intake prior to the
      competition consuming similar amounts to those athletes without diabetes, but
      consuming smaller quantities of CHO than the recommended amounts. This appears to
      induce a more stable glycemic response, in comparison with supplements with high
      CHO content. 

PMID- 25958942
TI  - Within-subject Variation of Thermoregulatory Responses during Repeated Exercise
      Bouts.
AB  - AIM: To assess the within-subject variation of thermoregulatory responses during
      2 consecutive 15-km road races. Secondly, we explored whether gastrointestinal
      temperature (TGI) data from the first race could improve our previously
      established predictive model for finish TGI in the second race. METHODS: We
      measured TGI before and immediately after both races in 58 participants and
      determined correlation coefficients. Finish TGI in the second race was predicted
      using a linear regression analysis including age, BMI, pre-race fluid intake, TGI
      increase between baseline and the start of the race and finish TGI in the first
      race. RESULTS: Under cool conditions (WBGT 11-12 degrees C), TGI was comparable
      between both races at baseline (37.6+/-0.4 degrees C vs. 37.9+/-0.4 degrees C;
      p=0.24) and finish (39.4+/-0.6 degrees C vs. 39.4+/-0.6 degrees C; p=0.83).
      Finish TGI correlated significantly between both races (r=0.50; p<0.001). The
      predictive model (p<0.001) could predict 32.2% of the finish TGI in the second
      race (vs. 17.1% without finish TGI in race 1). CONCLUSION: Our findings
      demonstrate that the use of previously obtained thermoregulatory responses
      results in higher predictability of finish core body temperatures in future
      races, enabling better risk assessment for those athletes that are most likely to
      benefit from preventive measures.

PMID- 25958943
TI  - Longitudinal Development of Explosive Leg Power from Childhood to Adulthood in
      Soccer Players.
AB  - The aim of the this study was to investigate the development of explosive leg
      power by using 2 similar jumping protocols (countermovement jump and standing
      broad jump) in 555 Belgian, high-level young soccer players, aged between 7 and
      20 years. The total sample was divided into 3 longitudinal samples related to
      growth and maturation (pre-teenchildhood: (6-10 years;), early adolescence: (11
      16 years;) and late adolescence: (17-20 years)), and 6 multilevel regression
      models were obtained. Generally, both jumping protocols emphasized that
      chronological age, body size dimensions (by means of fat mass in the late
      childhood and early adolescence groups, fat-free mass in the late adolescence
      group and stature--(not for CMJ in late childhood group) and fat mass in the late
      childhood and early adolescence groups, and fat-free mass in the late adolescence
      group) and motor coordination (one item of a 3-component test battery) are
      longitudinal predictors of explosive leg power from childhood to young adulthood.
      The contribution of maturational status was not investigated in this study. The
      present findings highlight the importance of including non-specific motor
      coordination in soccer talent development programs.

PMID- 25958944
TI  - External Responsiveness of the Yo-Yo IR Test Level 1 in High-level Male Soccer
      Players.
AB  - The aim of this study was to assess the external responsiveness, construct
      validity and internal responsiveness of the Yo-Yo Intermittent Recovery test
      level 1 and its sub-maximal version in semi-professional players. Tests and
      friendly matches were performed during the preseason and regular season. The
      distance covered above 15 km.h(-1) was considered as an indicator of the physical
      match performance. Construct validity and external responsiveness were examined
      by correlations between test and physical match performance (preseason and
      regular season) and training-induced changes. Internal responsiveness was
      determined as Cohen's effect size, standardized response mean and signal-to-noise
      ratio. The physical match performance increased after training (34.8%). The Yo-Yo
      Intermittent Recovery test level 1 improved after training (40.2%), showed
      longitudinal (r=0.69) and construct validity (r=0.73 and 0.59, preseason and
      regular season) and had higher internal responsiveness compared to its sub
      maximal version. The heart rate at the 6(th) minute in the sub-maximal version
      did not show longitudinal (r=-0.38) and construct validity (r=0.01 and -0.06,
      preseason and regular season) and did not significantly change after training (
      0.3%). The rate of perceived exertion decreased in the sub-maximal version (-
      29.8%). In conclusion, the Yo-Yo Intermittent Recovery test level 1 is valid and
      responsive, while the validity of its sub-maximal version is questionable. 

PMID- 25958945
TI  - Planned Overreaching and Subsequent Short-term Detraining Enhance Cycle Sprint
      Performance.
AB  - We investigated the effect of a training program consisting of planned
      overreaching and subsequent short-term detraining on sprint performance. 24
      physically active men participated in an 18-day sprint-training program. They
      were divided into 2 groups: the overreaching-detraining (OR-DT) and the control
      (CON) groups. Subjects in the OR-DT group performed 12 consecutive days of
      maximal cycle sprint training followed by 6 days of detraining, whereas a rest
      day was provided after every 2 successive training days for the CON group. Peak
      power output during maximal pedaling increased significantly after 6 days of
      detraining in the OR-DT group compared with the baseline (P<0.05), whereas no
      change was observed in CON group. Intramuscular phosphocreatine concentration
      increased significantly after 12 days of daily training in the OR-DT group
      (69.3+/-45.8% increase vs. baseline, P<0.05), and it was maintained after the
      detraining period (46.6+/-33.6% increase vs. baseline, P<0.05). However, no
      change was observed in CON group. No significant changes in blood variables were
      observed after the training period except significant reduction of serum cortisol
      in the CON group. Daily sprint training and subsequent short-term detraining
      enhanced peak power output after the detraining period. 

PMID- 25958946
TI  - Influence of Strength, Sprint Running, and Combined Strength and Sprint Running
      Training on Short Sprint Performance in Young Adults.
AB  - The purpose of this study was to assess the degree of transference of 6 weeks of
      full squat vs. full squat plus sprint running training to short (ranged from 0-10
      to 0-30 m) sprint running performance in non-athletes. We hypothesized that a
      speed-full-squat training regimen could enhance squat strength and power with
      simultaneous improvements in short sprint performance. 122 physically active
      adults (age: 20.5+/-2.5 years; body mass: 65.8+/-6.1 kg; height: 1.71+/-0.08 m)
      were randomly divided into 4 groups: full squat training (n=36), combined full
      squat and sprint training (n=32), speed training only (n=34) and non-training
      control group (n=20). Each training group completed 2 sessions per week over 6
      weeks, while the control group performed only their normal physical activity.
      Sprint performance was improved after sprint running or full squat training alone
      (1.7% and 1.8% P<0.05, respectively), however larger enhancements (2.3%; P<0.01)
      were observed after the combined full squat plus sprint training intervention.
      These results suggest that in recreationally active adults, combined full squat
      and sprint training provides a greater stimulus for improving sprint performance
      than either modality alone. 

PMID- 25958947
TI  - Crisis as a serendipity for change in Cyprus' healthcare services.
AB  - As Cyprus signed a financial agreement with a team of international lenders,
      several reform measures were outlined as pre-requisites for disbursement of
      financial instalments. The health sector was massively reformed in order to
      enhance efficiency and reduce waste. The magnitude of reforms included
      introduction of guidelines and clinical algorithms, co-payments, and revision of
      criteria for public beneficiary status. In order to safeguard equity in access,
      solidarity in coverage and sustainability of its healthcare sector, reforms must
      continue unabated and, more importantly, the introduction of a universal health
      system should be the ultimate goal. 

PMID- 25958949
TI  - Snacking between main meals is associated with a higher risk of metabolic
      syndrome in a Mediterranean cohort: the SUN Project (Seguimiento Universidad de
      Navarra).
AB  - OBJECTIVE: To evaluate the association of snacking between main meals with the
      risk of developing metabolic syndrome. DESIGN: A dynamic prospective cohort study
      (the SUN Project; Seguimiento Universidad de Navarra). Snack consumption was
      evaluated using the question: 'Do you have the habit of snacking between main
      meals?' Metabolic syndrome was defined according to the updated harmonizing
      criteria. We estimated multivariable-adjusted relative risks (RR) of metabolic
      syndrome and their 95 % confidence intervals using Poisson regression models. An
      exploratory factor analysis was also used to identify patterns of snacking.
      SETTING: University of Navarra, Spain. SUBJECTS: The study included 6851
      university graduates, initially free of metabolic syndrome, and followed-up them
      for a median of 8.3 years. RESULTS: Among our participants, 34.6% reported usual
      snacking between main meals. The cumulative incidence of metabolic syndrome was
      5.1 % (9.5% among men and 2.8% among women). Snacking between main meals was
      significantly associated with higher risk for developing metabolic syndrome after
      multivariable adjustment (RR=1.44; 95%CI 1.18, 1.77). Higher adherence to an
      'unhealthy snacking pattern' was also independently associated with increased
      incidence of metabolic syndrome (fourth quartile of adherence compared with non
      snacking: RR=1.68; 95% CI 1.23, 2.29; P for trend <0.001). CONCLUSIONS: Our
      findings suggest that avoidance of snacking between main meals can be included
      among the preventive approaches to reduce the risk of metabolic syndrome
      development, especially when snacks contain foods of poor nutritional quality.

PMID- 25958950
TI  - Amyophatic dermatomyositis presenting as a flagellated skin eruption with
      positive MDA5 antibodies and thyroid cancer: a real association?
AB  - Amyopathic dermatomyositis (ADM) is characterized clinically by typical skin
      lesions with hypomyopathy or no muscular involvement. ADM has been recently
      reported to be complicated by rapidly progressive interstitial lung disease
      (ILD), especially in patients with positive antibodies against melanoma
      differentiation-associated gene 5 (MDA5). These patients may have a low risk of
      cancer, but no clinical, histological or laboratory markers completely specific
      for paraneoplastic DM have been identified to date. We report a case of
      flagellate erythema as the initial presentation of ADM associated with ILD,
      positive MDA5 antibodies and a concomitant diagnosis of thyroid cancer. We
      discuss the unusual clinical features and associations that make this case
      particularly interesting. 

PMID- 25958948
TI  - FOXO responses to Porphyromonas gingivalis in epithelial cells.
AB  - Porphyromonas gingivalis is a prominent periodontal, and emerging systemic,
      pathogen that redirects host cell signalling pathways and modulates innate immune
      responses. In this study, we show that P. gingivalis infection induces the
      dephosphorylation and activation of forkhead box-O (FOXO)1, 3 and 4 in gingival
      epithelial cells. In addition, immunofluorescence showed that FOXO1 accumulated
      in the nucleus of P. gingivalis-infected cells. Quantitative reverse
      transcription PCR demonstrated that transcription of genes involved in protection
      against oxidative stress (Cat, Sod2, Prdx3), inflammatory responses (IL1beta) and
      anti-apoptosis (Bcl-6) was induced by P. gingivalis, while small-interfering RNA
      (siRNA)-mediated knockdown of FOXO1 suppressed the transcriptional activation of
      these genes. P. gingivalis-induced secretion of interleukin (IL)-1beta and
      inhibition of apoptosis were also impeded by FOXO1 knockdown. Neutralization of
      reactive oxygen species (ROS) by N-acetyl-l-cysteine blocked the activation of
      FOXO1 by P. gingivalis and concomitantly suppressed the activation of oxidative
      stress responses, anti-apoptosis programmes and IL-beta production. Inhibition of
      c-Jun-N-terminal kinase (JNK) either pharmacologically or by siRNA, reduced FOXO1
      activation and downstream FOXO1-dependent gene regulation in response to P.
      gingivalis. The results indicate that P. gingivalis-induced ROS activate FOXO
      transcription factors through JNK signalling, and that FOXO1 controls oxidative
      stress responses, inflammatory cytokine production and cell survival. These data
      position FOXO as an important signalling node in the epithelial cell-P.
      gingivalis interaction, with particular relevance to cell fate and dysbiotic host
      responses. 

PMID- 25958951
TI  - Predicting the degree of aromaticity of novel carbaporphyrinoids.
AB  - Magnetically induced current densities have been calculated for dioxaporphyrin,
      dithiaporphyrin, true carbaporphyrins, and N-confused porphyrins using the gauge
      including magnetically induced current (GIMIC) method. The current-strength
      susceptibilities (current strengths) have been obtained by numerically
      integrating the current flow passing selected chemical bonds. The current
      strength calculations yield very detailed information about the electron
      delocalization pathways of the molecules. The strength of the ring-current that
      circles around the porphyrinoid macroring is used to estimate the degree of
      molecular aromaticity. The studied porphyrinoid structures have been obtained by
      replacing the NH and N groups of porphin with formally isoelectronic moieties
      such as O, S, CH and CH2. Replacing an NH moiety of trans-porphin with
      isoelectronic O and S does not significantly change the current strengths and
      pathways, whereas substitution of N with an isoelectronic CH group leads to
      significant changes in the current pathway and current strengths. CH2 groups cut
      the flow of diatropic currents, whereas in strongly antiaromatic molecules a
      significant fraction of the paratropic ring-current is able to pass the sp(3)
      hybridized inner carbons. N-confused porphyrinoids sustain a ring current whose
      strength is about half the ring-current strength of porphin with the dominating
      current flow along the outer pathway via the NH moiety. When no hydrogen is
      attached to the inner carbon of the inverted pyrrolic ring, the current prefers
      the inner route at that ring. 

PMID- 25958952
TI  - Spontaneous formation of Cu2O-g-C3N4 core-shell nanowires for photocurrent and
      humidity responses.
AB  - The assembly of low dimensional g-C3N4 structures in a geometrically well-defined
      fashion and the complexation of g-C3N4 with other materials are the main
      approaches to construct fancy structures for special functions. While high
      temperature was often indispensable for the preparation process, the realization
      of room temperature assembly of the low dimensional g-C3N4 and the preparation of
      g-C3N4-based semiconductor composites will provide many additional advantages for
      new functional materials and applications. Herein, the unique cuprous oxide
      (Cu2O)-graphitic carbon nitrides (g-C3N4) core-shell nanowires with highly
      hierarchical sharp edges on the surface have been prepared by a spontaneous
      reduction and assembly approach based on oxygen-functional g-C3N4 (O-functional g
      C3N4) at room temperature. Combined with the hybrid effect of Cu2O with g-C3N4,
      such hierarchical Cu2O-g-C3N4 core-shell nanowires possess sensitivity to
      humidity and photocurrent response. 

PMID- 25958953
TI  - In situ synthesis of Na2Ti7O15 nanotubes on a Ti net substrate as a high
      performance anode for Na-ion batteries.
AB  - Na2Ti7O15 nanotubes on a Ti net substrate were fabricated for the first time and
      used directly as a binder-free anode for Na-ion batteries. This material
      exhibited high reversible capacity and excellent stability which might be due to
      its unique characteristics including the porous substrate, nanoscale large
      surface area, nanotube structure and so on. 

PMID- 25958954
TI  - Accurate and efficient linear scaling DFT calculations with universal
      applicability.
AB  - Density functional theory calculations are computationally extremely expensive
      for systems containing many atoms due to their intrinsic cubic scaling. This fact
      has led to the development of so-called linear scaling algorithms during the last
      few decades. In this way it becomes possible to perform ab initio calculations
      for several tens of thousands of atoms within reasonable walltimes. However, even
      though the use of linear scaling algorithms is physically well justified, their
      implementation often introduces some small errors. Consequently most
      implementations offering such a linear complexity either yield only a limited
      accuracy or, if one wants to go beyond this restriction, require a tedious fine
      tuning of many parameters. In our linear scaling approach within the BigDFT
      package, we were able to overcome this restriction. Using an ansatz based on
      localized support functions expressed in an underlying Daubechies wavelet basis -
      which offers ideal properties for accurate linear scaling calculations - we
      obtain an amazingly high accuracy and a universal applicability while still
      keeping the possibility of simulating large system with linear scaling walltimes
      requiring only a moderate demand of computing resources. We prove the
      effectiveness of our method on a wide variety of systems with different boundary
      conditions, for single-point calculations as well as for geometry optimizations
      and molecular dynamics. 

PMID- 25958955
TI  - Metal-organic frameworks: versatile heterogeneous catalysts for efficient
      catalytic organic transformations.
AB  - Novel catalytic materials are highly demanded to perform a variety of catalytic
      organic reactions. MOFs combine the benefits of heterogeneous catalysis like easy
      post reaction separation, catalyst reusability, high stability and homogeneous
      catalysis such as high efficiency, selectivity, controllability and mild reaction
      conditions. The possible organization of active centers like metallic nodes,
      organic linkers, and their chemical synthetic functionalization on the nanoscale
      shows potential to build up MOFs particularly modified for catalytic challenges.
      In this review, we have summarized the recent research progress in heterogeneous
      catalysis by MOFs and their catalytic behavior in various organic reactions,
      highlighting the key features of MOFs as catalysts based on the active sites in
      the framework. Examples of their post functionalization, inclusion of active
      guest species and metal nanoparticles have been discussed. Finally, the use of
      MOFs as catalysts for asymmetric heterogeneous catalysis and stability of MOFs
      has been presented as separate sections. 

PMID- 25958956
TI  - Predicting genetic interactions from Boolean models of biological networks.
AB  - Genetic interaction can be defined as a deviation of the phenotypic quantitative
      effect of a double gene mutation from the effect predicted from single mutations
      using a simple (e.g., multiplicative or linear additive) statistical model.
      Experimentally characterized genetic interaction networks in model organisms
      provide important insights into relationships between different biological
      functions. We describe a computational methodology allowing us to systematically
      and quantitatively characterize a Boolean mathematical model of a biological
      network in terms of genetic interactions between all loss of function and gain of
      function mutations with respect to all model phenotypes or outputs. We use the
      probabilistic framework defined in MaBoSS software, based on continuous time
      Markov chains and stochastic simulations. In addition, we suggest several
      computational tools for studying the distribution of double mutants in the space
      of model phenotype probabilities. We demonstrate this methodology on three
      published models for each of which we derive the genetic interaction networks and
      analyze their properties. We classify the obtained interactions according to
      their class of epistasis, dependence on the chosen initial conditions and the
      phenotype. The use of this methodology for validating mathematical models from
      experimental data and designing new experiments is discussed. 

PMID- 25958957
TI  - Gamma Knife radiosurgery for cystic brain metastases.
AB  - OBJECTIVE: The goal of this study was to investigate the treatment results of
      Gamma Knife radiosurgery (GKRS) for cystic brain metastases and relevant factors
      associated with local tumor control. MATERIALS AND METHODS: We retrospectively
      reviewed the clinical, radiological, and dosimetry data of 37 cystic brain
      metastases of 28 patients who were treated with GKRS. Cyst drainage was performed
      in 8 large lesions before GKRS to decrease the target volume. The mean target
      volume was 4.8 (range, 0.3-15.8) cc at the time of GKRS, and the mean
      prescription dose was 16.6 (range, 13-22) Gy. RESULTS: The actuarial median
      survival time was 17.7 +/- 10.2 months, and the primary tumor status was a
      significant prognostic factor for survival. The actuarial local tumor control
      rate at 6 and 12 months was 93.1 and 82.3%, respectively. Among the various
      factors, only prescription dose (>15 Gy) was a significant factor related to
      local tumor control after multivariate analysis (p = 0.049). Cyst volume or
      cyst/total tumor volume ratio did not influence local control after GKRS, when
      the target volume was reduced to about 15 cc after cyst drainage. CONCLUSION:
      According to our results, we suggest that stereotactic radiosurgery should be
      considered as one of the treatment options for cystic brain metastases, when
      large tumor volume can be reduced by surgical drainage before radiosurgery,
      especially for patients with a controlled primary tumor.

PMID- 25958958
TI  - Decompressive craniectomy arrests pulsatile aqueductal CSF flux: An in vivo
      demonstration using phase-contrast MRI. Case report.
AB  - We give a case study demonstration, using aqueductal cerebrospinal fluid (CSF)
      stroke volume quantification with phase-contrast magnetic resonance imaging, of a
      large opening in the rigid cranium by a decompressive craniectomy and its
      subsequent closure by bone flap repositioning resulted in the arrest and
      subsequent restoration of aqueductal CSF flow. 

PMID- 25958959
TI  - Traumatic lumbar artery rupture after lumbar spinal fracture dislocation causing
      hypovolemic shock: An endovascular treatment.
AB  - Recently, we observed a case of lumbar artery injury after trauma, which was
      treated by endovascular embolization. A 67-year-old woman who was injured in a
      traffic accident was brought to the emergency room. She was conscious and her
      hemodynamic condition was stable, but she had paraplegia below L1 dermatome.
      Contrast-enhanced computed tomography scan of abdomen and pelvis revealed
      fracture dislocation of L3/4 along with retroperitoneal hematomas. However, there
      was no evidence of traumatic injury in both thoracic and abdominal cavity. At
      that time, her blood pressure suddenly decreased to 60/40 mmHg and her mental
      status deteriorated. Also, her hemoglobin level was 5.4 g/dl. While her
      hemodynamic condition stabilized with massive fluid resuscitation including blood
      transfusion, an angiography was immediately performed to look for and embolize
      site of retroperitoneal hemorrhage. On the angiographic images, there was an
      active extravasation from ruptured left 3rd lumbar artery, and we performed
      complete embolization with GELFOAM and coil. Lumbar artery injury after trauma is
      rare and endovascular treatment is useful in case of hemodynamic instability. 

PMID- 25958960
TI  - Case report: Recurrent glossopharyngeal neuralgia after previous glossopharyngeal
      rhizotomy: Microvascular decompression with intra-operative neurophysiology.
AB  - We present a case of recurrent vago-glossopharyngeal neuralgia after previous
      surgery, treated successfully with microvascular decompression using intra
      operative neurophysiology monitoring. 

PMID- 25958961
TI  - The ecological validity of the autonomic-subjective response dissociation in
      repressive coping.
AB  - BACKGROUND AND OBJECTIVES: Repressive coping has been associated with elevated
      cardiovascular reactivity and diminished self-reported negative affect (so-called
      autonomic-subjective response dissociation, ASRD) in response to laboratory
      stressors. However, there is a lack of knowledge regarding the ecological
      validity of this response pattern. DESIGN: An ambulatory assessment strategy was
      applied in order to analyze associations between ASRD and repressive coping
      throughout a day. METHODS: A sample of 114 individuals was recruited. Heart rate
      was recorded via ECG and subjective reports of negative affect as well as the
      experience of demand and control (as indicators of stress) and situational
      characteristics were assessed several times a day via mobile electronic devices.
      RESULTS: Repressive coping relative to other coping dispositions was accompanied
      by elevated ASRD during stressful episodes in daily life, thus supporting
      previous laboratory research. CONCLUSIONS: The findings suggest that repressive
      coping is associated with a discrepancy between subjective reports of negative
      affect and autonomic responding to stressful encounters in everyday life, which
      might impact health.

PMID- 25958962
TI  - para-Sulphonato-calix[n]arenes as selective activators for the passage of
      molecules across the Caco-2 model intestinal membrane.
AB  - The passage of Lucifer Yellow across the Caco-2 intestinal model membrane has
      been studied for the para-sulphonato-calix[n]arenes, the results show that para
      sulphonato-calix[4]arene and para-sulphonato-calix[8]arene activate membrane
      passage when used simultaneously with a transport probe, Lucifer Yellow, whereas
      para-sulphonato-calix[6]arene has no effect. 

PMID- 25958963
TI  - Cost-effectiveness analysis of axitinib through a probabilistic decision model.
AB  - INTRODUCTION: The Oncology field is characterised by a steady increase in demand
      and a consistent launching of innovative and expensive products. Therefore, cost
      effectiveness analysis can contribute as a significant decision-making tool by
      elucidating the most economically efficient ways to satisfy compelling health
      needs. AREAS COVERED: The scope of this study is to estimate the cost
      effectiveness of axitinib versus sorafenib, for the second-line treatment of
      renal cell carcinoma. A literature review for evidence synthesis was performed
      and a probabilistic Markov Model was employed to simulate disease progression.
      This study will also assess Value of Information. EXPERT OPINION: Compared to
      sorafenib, axitinib resulted in an incremental cost of 87,936 euro per quality
      adjusted life year. The probability of axitinib to being cost-effective at the
      willingness-to-pay threshold of 60,000 euro was 13%, while the corresponding
      probability of being cost-effective at the highest recommended willingness-to-pay
      threshold of 100,000 euro was 69.9%. Uncertainty was primarily attributed to the
      price of the product, the utility values, the progression-free survival and to a
      lesser degree to the overall survival. Axitinib can be considered as a cost
      effective therapeutic option for second-line treatment of renal cell carcinoma.

PMID- 25958964
TI  - Combination phentermine and topiramate extended release in the management of
      obesity.
AB  - INTRODUCTION: Losing >= 5% of initial weight improves quality of life and risk
      factors for cardiovascular disease (CVD) in obese individuals. Lifestyle
      modification, the cornerstone of weight reduction, may be complemented by
      pharmacotherapy. In 2012, the FDA approved the combination of phentermine and
      topiramate extended release (ER) for chronic weight management, as an adjunct to
      lifestyle modification. AREAS COVERED: This review examines the safety and
      efficacy of phentermine-topiramate ER, as determined by randomized controlled
      trials (RCTs). A preliminary study confirmed the benefit of combining the two
      medications for improving weight loss and reducing adverse effects, as compared
      to using equivalent-dose monotherapy alone. EXPERT OPINION: Across RCTs, groups
      prescribed phentermine 15 mg/topiramate ER 92 mg lost an average of 10% of
      initial weight, ~ 8% more than placebo and 2% more than phentermine 7.5
      mg/topiramate 46 mg. Weight loss reduced the risk of developing type 2 diabetes
      and improved CVD risk factors. Phentermine-topiramate ER, however, was associated
      with increased heart rate, the clinical significance of which is being
      investigated in an FDA-required CVD outcomes study. The medication also must be
      used with caution in women of child-bearing age because of an increased risk to
      infants of oral cleft.

PMID- 25958966
TI  - Correlation of disease activity and serum level of carcinoembryonic antigen in
      acquired idiopathic generalized anhidrosis: A case report.
AB  - Hypohidrosis and anhidrosis are congenital or acquired conditions which are
      characterized by inadequate sweating. Acquired idiopathic generalized
      hypohidrosis/anhidrosis (AIGA) includes idiopathic pure sudomotor failure (IPSF),
      which has the following distinct features: sudden onset in youth, increased serum
      immunoglobulin E and responds favorably to systemic corticosteroid. No clinical
      markers reflecting the disease severity or activity have been established. Here,
      we report a case of AIGA in a Japanese patient successfully treated with repeated
      methylprednisolone pulse therapy. In this case, serum carcinoembryonic antigen
      (CEA) levels increased up to 19.8 ng/mL along with aberrant CEA immunoreactivity
      of eccrine sweat glands. Interestingly, the serum CEA level normalized as
      sweating improved with repeated methylprednisolone pulse therapy. Therefore,
      serum CEA level may serve as a useful clinical marker of hypohidrosis or
      anhidrosis. 

PMID- 25958967
TI  - Synthesis and evaluation of cationic norbornanes as peptidomimetic antibacterial
      agents.
AB  - A series of structurally amphiphilic biscationic norbornanes have been
      synthesised as rigidified, low molecular weight peptidomimetics of cationic
      antimicrobial peptides. A variety of charged hydrophilic functionalities were
      attached to the norbornane scaffold including aminium, guanidinium, imidazolium
      and pyridinium moieties. Additionally, a range of hydrophobic groups of differing
      sizes were incorporated through an acetal linkage. The compounds were evaluated
      for antibacterial activity against both Gram-negative and Gram-positive bacteria.
      Activity was observed across the series; the most potent of which exhibited an
      MIC's <= 1 MUg mL(-1) against Streptococcus pneumoniae, Enterococcus faecalis and
      several strains of Staphylococcus aureus, including multi-resistant methicillin
      resistant (mMRSA), glycopeptide-intermediate (GISA) and vancomycin-intermediate
      (VISA) S. aureus. 

PMID- 25958968
TI  - Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE)
      associated with psoriatic arthritis.

PMID- 25958969
TI  - Nitrogen assimilation and transpiration: key processes conditioning
      responsiveness of wheat to elevated [CO2] and temperature.
AB  - Although climate scenarios have predicted an increase in [CO(2)] and temperature
      conditions, to date few experiments have focused on the interaction of [CO(2)]
      and temperature effects in wheat development. Recent evidence suggests that
      photosynthetic acclimation is linked to the photorespiration and N assimilation
      inhibition of plants exposed to elevated CO(2). The main goal of this study was
      to analyze the effect of interacting [CO(2)] and temperature on leaf
      photorespiration, C/N metabolism and N transport in wheat plants exposed to
      elevated [CO(2)] and temperature conditions. For this purpose, wheat plants were
      exposed to elevated [CO(2)] (400 vs 700 umol mol(-1)) and temperature (ambient vs
      ambient + 4 degrees C) in CO(2) gradient greenhouses during the entire life
      cycle. Although at the agronomic level, elevated temperature had no effect on
      plant biomass, physiological analyses revealed that combined elevated [CO(2)] and
      temperature negatively affected photosynthetic performance. The limited energy
      levels resulting from the reduced respiratory and photorespiration rates of such
      plants were apparently inadequate to sustain nitrate reductase activity.
      Inhibited N assimilation was associated with a strong reduction in amino acid
      content, conditioned leaf soluble protein content and constrained leaf N status.
      Therefore, the plant response to elevated [CO(2)] and elevated temperature
      resulted in photosynthetic acclimation. The reduction in transpiration rates
      induced limitations in nutrient transport in leaves of plants exposed to elevated
      [CO(2)] and temperature, led to mineral depletion and therefore contributed to
      the inhibition of photosynthetic activity.

PMID- 25958971
TI  - Promoting physical health for people with schizophrenia by reducing disparities
      in medical and dental care.
AB  - OBJECTIVE: Acquiring a diagnosis of schizophrenia reduces life expectancy for
      many reasons including poverty, difficulties in communication, side-effects of
      medication and access to care. This mortality gap is driven by natural deaths;
      cardiovascular disease is a major cause, but outcomes for people with severe
      mental illness are worse for many physical health conditions, including cancer,
      fractures and complications of surgery. We set out to examine the literature on
      disparities in medical and dental care experienced by people with schizophrenia
      and suggest possible approaches to improving health. METHOD: This narrative
      review used a targeted literature search to identify the literature on physical
      health disparities in schizophrenia. RESULTS: There is evidence of inequitable
      access to and/or uptake of physical and dental health care by those with
      schizophrenia. CONCLUSION: The goal was to reduce the mortality gap through
      equity of access to all levels of health care, including acute care, long-term
      condition management, preventative medicine and health promotion. We suggest
      solutions to promote health, wellbeing and longevity in this population,
      prioritising identification of and intervention for risk factors for premature
      morbidity and mortality. Shared approaches are vital, while joint education of
      clinicians will help break down the artificial mind-body divide.

PMID- 25958972
TI  - Eye size and shape in newborn children and their relation to axial length and
      refraction at 3 years.
AB  - PURPOSE: To determine if eye size and shape at birth are associated with eye size
      and refractive error 3 years later. METHODS: A subset of 173 full-term newborn
      infants from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth
      cohort underwent magnetic resonance imaging (MRI) to measure the dimensions of
      the internal eye. Eye shape was assessed by an oblateness index, calculated as 1 
      (axial length/width) or 1 - (axial length/height). Cycloplegic autorefraction
      (Canon Autorefractor RK-F1) and optical biometry (IOLMaster) were performed 3
      years later. RESULTS: Both eyes of 173 children were analysed. Eyes with longer
      axial length at birth had smaller increases in axial length at 3 years (p <
      0.001). Eyes with larger baseline volumes and surface areas had smaller increases
      in axial length at 3 years (p < 0.001 for both). Eyes which were more oblate at
      birth had greater increases in axial length at 3 years (p < 0.001). Using width
      to calculate oblateness, prolate eyes had smaller increases in axial length at 3
      years compared to oblate eyes (p < 0.001), and, using height, prolate and
      spherical eyes had smaller increases in axial length at 3 years compared to
      oblate eyes (p < 0.001 for both). There were no associations between eye size and
      shape at birth and refraction, corneal curvature or myopia at 3 years.
      CONCLUSIONS: Eyes that are larger and have prolate or spherical shapes at birth
      exhibit smaller increases in axial length over the first 3 years of life. Eye
      size and shape at birth influence subsequent eye growth but not refractive error
      development.

PMID- 25958973
TI  - Value of microwave ablation in treatment of large lesions of hepatocellular
      carcinoma.
AB  - OBJECTIVE: Thermal ablative therapies continue to be favored as a safe and
      effective treatment for patients with non-resectable hepatocellular carcinoma
      (HCC). Percutaneous microwave ablative therapy, which is a relatively new
      technique, has the advantage in providing faster ablation of large tumors. This
      study aimed to evaluate microwave ablation in the treatment of large HCC (5-7 cm)
      and to assess its effect on local tumor progression, prognostic outcome and
      patients' survival. METHODS: In all, 26 patients with large HCC lesions (5-7 cm)
      were managed in the multidisciplinary clinic of Kasr Al Ainy University hospital
      using microwave ablation. The treatment was performed with the patient under
      conscious sedation and analgesia and ultrasonography-guided using an HS AMICA
      microwave machine operating at frequency of 2450 MHz and a power up to 100 W.
      Multiple needle insertions were made in one or two sessions according to the size
      of the lesion. The complete ablation rate, local tumor progression and patients'
      overall survival were analyzed, and the efficacy and safety of MWA was evaluated.
      RESULTS: Complete ablation was achieved in 19/26 (73.1%). Local tumor progression
      was recorded in five treated lesions (19.2%). Distant tumor progression within
      the liver was recorded in six patients (23.1%), with a mean survival of 21.5
      months. No procedure-related major complications or deaths were observed.
      CONCLUSIONS: Percutaneous microwave ablation is safe and effective in the
      treatment of large HCC tumors. Patients' survival and local tumor control were
      acceptable.

PMID- 25958974
TI  - The association between rotating shift work and increased occupational stress in
      nurses.
AB  - PURPOSE: The aim of this study was to investigate whether rotating shift work
      increases occupational stress in nurses. METHODS: This study measured shift work
      scheduling and occupational stress by using the Effort-Reward Imbalance model
      with self-reported questionnaires in a sample of 654 female nurses. RESULTS:
      Overcommitment risk was higher in nurses who worked rotating shifts than in those
      who worked day/non-night shifts (OR, 2.16; 95% CI, 1.03-4.66). However, an
      effort/reward imbalance was not directly associated with work schedules (OR,
      1.88; 95% CI, 0.87-4.35). Among nurses working rotation rotating shifts, those
      who had 2 days off after their most recent night shifts showed an alleviated risk
      of overcommitment (OR, 0.52; 95% CI, 0.32-0.82), but those who had worked for at
      least one series of 7 consecutive work days per month had an increased risk of
      effort/reward imbalance (OR, 2.75; 95% CI, 1.69-4.48). Additionally, those who
      had little or no participation in planning working hours and shift scheduling and
      worked overtime at least three times per week during the preceding 2 months
      tended to have high stress. CONCLUSIONS: The nurses who worked rotating shifts
      tended to experience work-related stress, but their stress levels improved if
      they had at least 2 days off after their most recent night shift and if they were
      not scheduled to work 7 consecutive days. These empirical data can be used to
      optimize work schedules for nurses to alleviate work stress.

PMID- 25958975
TI  - Pulmonary effects in workers exposed to indium metal: A cross-sectional study.
AB  - OBJECTIVES: Indium was added to the list of substances regulated by the Ordinance
      on Prevention of Hazards due to Specified Chemical Substances (OPHSCS) in 2013.
      Indium metal (IM), however, is not regulated by the OPHSCS due to insufficient
      information on pulmonary effects following exposure. METHODS: From 2011 to 2013,
      a cross-sectional study was conducted on 141 IM-exposed workers at 11 factories.
      Subjective symptoms were assessed, including levels of serum biomarkers,
      spirometry readings and total and diffuse lung capacity. Krebs von den Lungen-6
      (KL-6) and surfactant protein D (SP-D) were selected as biomarkers of
      interstitial pneumonia. Indium serum concentration (In-S) and personal air
      sampling data were used to estimate exposure. Subjects were categorized into 5
      groups based on occupation and type of exposure: smelting, soldering, dental
      technician, bonding and other. RESULTS: The highest level of In-S was 25.4 ug/l,
      and the mean In-S level was significantly higher in the smelting group than in
      other groups. In the smelting group, the prevalence of increased In-S levels was
      9.1%, while that of abnormal KL-6 was 15.2%. A significant dose-effect
      relationship was observed between the In-S and KL-6 levels. No marked differences
      were observed between any of the groups in SP-D values, pulmonary symptoms, or
      pulmonary function test results. A total of 31% of the subjects worked in an
      environment with IM levels exceeding 0.3 ug/m(3), which requires a protective
      mask to be worn. CONCLUSIONS: For workers exposed to IM, work environments should
      be monitored, appropriate protective masks should be worn, and medical monitoring
      should be conducted according to the OPHSCS.

PMID- 25958976
TI  - Dimensionality of the 9-item Utrecht Work Engagement Scale revisited: A Bayesian
      structural equation modeling approach.
AB  - OBJECTIVES: The aim of this study was to reexamine the dimensionality of the
      widely used 9-item Utrecht Work Engagement Scale using the maximum likelihood
      (ML) approach and Bayesian structural equation modeling (BSEM) approach. METHODS:
      Three measurement models (1-factor, 3-factor, and bi-factor models) were
      evaluated in two split samples of 1,112 health-care workers using confirmatory
      factor analysis and BSEM, which specified small-variance informative priors for
      cross-loadings and residual covariances. Model fit and comparisons were evaluated
      by posterior predictive p-value (PPP), deviance information criterion, and
      Bayesian information criterion (BIC). RESULTS: None of the three ML-based models
      showed an adequate fit to the data. The use of informative priors for cross
      loadings did not improve the PPP for the models. The 1-factor BSEM model with
      approximately zero residual covariances displayed a good fit (PPP>0.10) to both
      samples and a substantially lower BIC than its 3-factor and bi-factor
      counterparts. CONCLUSIONS: The BSEM results demonstrate empirical support for the
      1-factor model as a parsimonious and reasonable representation of work
      engagement.

PMID- 25958977
TI  - Population genetic structure of Bombus terrestris in Europe: Isolation and
      genetic differentiation of Irish and British populations.
AB  - The genetic structure of the earth bumblebee (Bombus terrestris L.) was examined
      across 22 wild populations and two commercially reared populations using eight
      microsatellite loci and two mitochondrial genes. Our study included wild
      bumblebee samples from six populations in Ireland, one from the Isle of Man, four
      from Britain and 11 from mainland Europe. A further sample was acquired from New
      Zealand. Observed levels of genetic variability and heterozygosity were low in
      Ireland and the Isle of Man, but relatively high in continental Europe and among
      commercial populations. Estimates of Fst revealed significant genetic
      differentiation among populations. Bayesian cluster analysis indicated that Irish
      populations were highly differentiated from British and continental populations,
      the latter two showing higher levels of admixture. The data suggest that the
      Irish Sea and prevailing south westerly winds act as a considerable geographical
      barrier to gene flow between populations in Ireland and Britain; however, some
      immigration from the Isle of Man to Ireland was detected. The results are
      discussed in the context of the recent commercialization of bumblebees for the
      European horticultural industry. 

PMID- 25958980
TI  - Deriving persistence indicators from regulatory water-sediment studies -
      opportunities and limitations in OECD 308 data.
AB  - The OECD guideline 308 describes a laboratory test method to assess aerobic and
      anaerobic transformation of organic chemicals in aquatic sediment systems and is
      an integral part of tiered testing strategies in different legislative frameworks
      for the environmental risk assessment of chemicals. The results from experiments
      carried out according to OECD 308 are generally used to derive persistence
      indicators for hazard assessment or half-lives for exposure assessment. We used
      Bayesian parameter estimation and system representations of various complexities
      to systematically assess opportunities and limitations for estimating these
      indicators from existing data generated according to OECD 308 for 23 pesticides
      and pharmaceuticals. We found that there is a disparity between the uncertainty
      and the conceptual robustness of persistence indicators. Disappearance half-lives
      are directly extractable with limited uncertainty, but they lump degradation and
      phase transfer information and are not robust against changes in system geometry.
      Transformation half-lives are less system-specific but require inverse modeling
      to extract, resulting in considerable uncertainty. Available data were thus
      insufficient to derive indicators that had both acceptable robustness and
      uncertainty, which further supports previously voiced concerns about the
      usability and efficiency of these costly experiments. Despite the limitations of
      existing data, we suggest the time until 50% of the parent compound has been
      transformed in the entire system (DegT(50,system)) could still be a useful
      indicator of persistence in the upper, partially aerobic sediment layer in the
      context of PBT assessment. This should, however, be accompanied by a mandatory
      reporting or full standardization of the geometry of the experimental system. We
      recommend transformation half-lives determined by inverse modeling to be used as
      input parameters into fate models for exposure assessment, if due consideration
      is given to their uncertainty.

PMID- 25958979
TI  - An immediate peri-implantitis induction model to study regenerative peri
      implantitis treatments.
AB  - OBJECTIVES: The aim of this study was to evaluate the validity of the immediate
      peri-implantitis model to test regenerative therapies in peri-implantitis
      defects. MATERIAL AND METHODS: In an immediate peri-implantitis model in beagles,
      the mandibular third premolars were extracted, and dental implants were
      immediately placed in the distal extraction sockets. Without a healing period,
      experimental peri-implantitis was induced by ligature placement for 3 months. In
      the conventional peri-implantitis model, dental implants were placed in the
      healed mandibular fourth premolar region and were submerged for osseointegration.
      After 3 months of healing, peri-implantitis induction was performed for another 3
      months. After peri-implantitis defects were formed in both models, regenerative
      therapy was performed in both models. RESULTS: After 3 months in the immediate
      model and 9 months in the conventional model, similarly shaped horizontal bone
      defects (wide and craterlike) were observed. However, buccal bone defects were
      deeply formed in the immediate model compared with the conventional model (6.02
      +/- 1.20 and 4.34 +/- 0.86 mm, respectively; P = 0.009), but the amounts of bone
      regeneration were not significantly different between the models (P = 0.107). On
      the lingual side, re-osseointegration was significantly greater in the
      conventional model than in the immediate model (0.72 +/- 0.50 and 1.77 +/- 0.87
      mm, respectively; P = 0.009), although lingual bone defects were not
      significantly different between the models (P = 0.248). CONCLUSIONS: Although the
      immediate peri-implantitis model is challenging for regeneration, it may be able
      to replace the conventional model to study regenerative peri-implantitis
      treatment due to its short experimental time and similar defect configuration.

PMID- 25958978
TI  - Revisiting a measure of child postoperative recovery: development of the Post
      Hospitalization Behavior Questionnaire for Ambulatory Surgery.
AB  - BACKGROUND: The Post Hospitalization Behavior Questionnaire (PHBQ) was designed
      for assessing children's posthospitalization and postoperative new-onset
      behavioral changes. However, the psychometric properties of the scale have not
      been re-evaluated in the past five decades despite substantial changes in the
      practice of surgery and anesthesia. In this investigation, we examined the
      psychometric properties of the PHBQ to potentially increase the efficacy and
      relevance of the instrument in current perioperative settings. METHOD: This study
      used principal components analysis, a panel of experts, Cronbach's alpha, and
      correlations to examine the current subscale structure of the PHBQ and eliminate
      items to create the Post Hospitalization Behavior Questionnaire for Ambulatory
      Surgery (PHBQ-AS). Data from previous investigations (N = 1064, Mage  = 5.88)
      which utilized the PHBQ were combined for the purposes of this paper. RESULTS: A
      principal components analysis revealed that the original subscale structure of
      the PHBQ could not be replicated. Subsequently, a battery reduction, which
      utilized principal components analysis and a panel of experts, was used to
      eliminate the subscale structure of the scale and reduce the number of items from
      27 to 11, creating the PHBQ-AS. The PHBQ-AS demonstrated good internal
      consistency reliability and concurrent validity with another measure of
      children's psychosocial and physical functioning. CONCLUSION: Revising the former
      subscale structure and reducing the number of items in the PHBQ to create the
      PHBQ-AS may provide a means for reducing the burden of postoperative behavioral
      assessment through decreasing time of administration and eliminating redundancy
      of items and allow for more accurate measurement of child postoperative
      behavioral changes.

PMID- 25958981
TI  - Global gene deregulations in FASN silenced retinoblastoma cancer cells: molecular
      and clinico-pathological correlations.
AB  - Activation of fatty acid synthase (FASN) enzyme in the de novo lipogenic pathway
      has been reported in various cancers including retinoblastoma (RB), a pediatric
      ocular cancer. The present study investigates lipogenesis-dependent survival of
      RB cancer cells and the associated molecular pathways in FASN silenced RB cells.
      The siRNA-mediated FASN gene knockdown in RB cancer cells (Y79, WERI RB1)
      repressed FASN mRNA and protein expressions, and decreased cancer cell viability.
      Global gene expression microarray analysis was performed in optimized FASN siRNA
      transfected and untransfected RB cells. Deregulation of various downstream cell
      signaling pathways such as EGFR (n = 55 genes), TGF-beta (n = 45 genes), cell
      cycle (n = 41 genes), MAPK (n = 39 genes), lipid metabolism (n = 23 genes),
      apoptosis (n = 21 genes), GPCR signaling (n = 21 genes), and oxidative
      phosporylation (n = 18 genes) were observed. The qRT-PCR validation in FASN
      knockdown RB cells revealed up-regulation of ANXA1, DAPK2, and down-regulation of
      SKP2, SREBP1c, RXRA, ACACB, FASN, HMGCR, USP2a genes that favored the anti-cancer
      effect of lipogenic inhibition in RB. The expression of these genes in primary RB
      tumor tissues were correlated with FASN expression, based on their clinico
      pathological features. The differential phosphorylation status of the various
      PI3K/AKT pathway proteins (by western analysis) indicated that the FASN gene
      silencing indeed mediated apoptosis in RB cells through the PI3K/AKT pathway.
      Scratch assay clearly revealed that FASN silencing reduced the invading property
      of RB cancer cells. Dependence of RB cancer cells on lipid metabolism for
      survival and progression is implicated. Thus targeting FASN is a promising
      strategy in RB therapy.

PMID- 25958982
TI  - K63 linked ubiquitin chain formation is a signal for HIF1A degradation by
      Chaperone-Mediated Autophagy.
AB  - Chaperone-Mediated Autophagy is a selective form of autophagy. Recently, the
      degradation of a newly identified CMA substrate, the HIF1A transcription factor,
      was found to be regulated by the ubiquitin ligase STUB1. In this study we show,
      for the first time, that K63 ubiquitination is necessary for CMA degradation of
      HIF1A in vitro and in vivo. Additionally, STUB1 mediates K63 linked
      ubiquitination of HIF1A. Our findings add a new regulatory step and increase the
      specificity of the molecular mechanism involved in CMA degradation of HIF1A,
      expanding the role of ubiquitination to yet another biological process, since the
      same mechanism might be applicable to other CMA substrates. 

PMID- 25958983
TI  - Microchip electrophoresis with electrochemical detection for the determination of
      analytes in the dopamine metabolic pathway.
AB  - A method for the separation and detection of analytes in the dopamine metabolic
      pathway was developed using microchip electrophoresis with electrochemical
      detection. The microchip consisted of a 5 cm PDMS separation channel in a simple
      t configuration. Analytes in the dopamine metabolic pathway were separated using
      a background electrolyte composed of 15 mM phosphate at pH 7.4, 15 mM SDS, and
      2.5 mM boric acid. Two different microchip substrates using different electrode
      materials were compared for the analysis: a PDMS/PDMS device with a carbon fiber
      electrode and a PDMS/glass hybrid device with a pyrolyzed photoresist film carbon
      electrode. While the PDMS/PDMS device generated high separation efficiencies and
      good resolution, more reproducible migration times were obtained with the
      PDMS/glass hybrid device, making it a better choice for biological applications.
      Lastly, the optimized method was used to monitor l-DOPA metabolism in a rat brain
      slice. 

PMID- 25958984
TI  - An alternative parameterization of Bayesian logistic hierarchical models for
      mixed treatment comparisons.
AB  - Mixed treatment comparison (MTC) models rely on estimates of relative
      effectiveness from randomized clinical trials so as to respect randomization
      across treatment arms. This approach could potentially be simplified by an
      alternative parameterization of the way effectiveness is modeled. We introduce a
      treatment-based parameterization of the MTC model that estimates outcomes on both
      the study and treatment levels. We compare the proposed model to the commonly
      used MTC models using a simulation study as well as three randomized clinical
      trial datasets from published systematic reviews comparing (i) treatments on
      bleeding after cirrhosis, (ii) the impact of antihypertensive drugs in diabetes
      mellitus, and (iii) smoking cessation strategies. The simulation results suggest
      similar or sometimes better performance of the treatment-based MTC model.
      Moreover, from the real data analyses, little differences were observed on the
      inference extracted from both models. Overall, our proposed MTC approach
      performed as good, or better, than the commonly applied indirect and MTC models
      and is simpler, fast, and easier to implement in standard statistical software.

PMID- 25958985
TI  - Quantification of thickness and wrinkling of exfoliated two-dimensional zeolite
      nanosheets.
AB  - Some two-dimensional (2D) exfoliated zeolites are single- or near single-unit
      cell thick silicates that can function as molecular sieves. Although they have
      already found uses as catalysts, adsorbents and membranes precise determination
      of their thickness and wrinkling is critical as these properties influence their
      functionality. Here we demonstrate a method to accurately determine the thickness
      and wrinkles of a 2D zeolite nanosheet by comprehensive 3D mapping of its
      reciprocal lattice. Since the intensity modulation of a diffraction spot on
      tilting is a fingerprint of the thickness, and changes in the spot shape are a
      measure of wrinkling, this mapping is achieved using a large-angle tilt-series of
      electron diffraction patterns. Application of the method to a 2D zeolite with MFI
      structure reveals that the exfoliated MFI nanosheet is 1.5 unit cells (3.0 nm)
      thick and wrinkled anisotropically with up to 0.8 nm average surface roughness. 

PMID- 25958986
TI  - Postprandial metabolism in adults with Prader-Willi syndrome.
AB  - OBJECTIVE: Individuals with Prader-Willi syndrome (PWS) are commonly restricted
      to 60-75% of height-appropriate calorie intake because they rapidly become obese
      on a normal diet. This study measured changes in energy expenditure, glucose and
      lipid homeostasis, and metabolic flexibility in response to a meal in PWS adults.
      METHODS: 11 adults with PWS were compared with 12 adiposity-matched and 10 lean
      subjects. Indirect calorimetry was conducted at baseline and 210 min after a
      standardized 600 kCal breakfast to assess energy expenditure and substrate
      utilization. Circulating glucose, insulin, C-peptide, glucagon, nonesterified
      fatty acids, and triglycerides were measured up to 240 min. Insulin sensitivity
      and insulin secretion rate were assessed by HOMA-IR and C-peptide deconvolution,
      respectively. Body composition was determined by dual-energy X-ray
      absorptiometry. RESULTS: The PWS group had lower lean mass than the obesity
      control group. Corrected for lean mass, there were no differences between the PWS
      and obesity groups in resting metabolic rate or metabolic flexibility. Total and
      abdominal fat mass, insulin sensitivity, and insulin secretion rate were also
      similar between these groups. CONCLUSIONS: This study did not detect an intrinsic
      metabolic defect in individuals with PWS. Rather, lower lean mass, combined with
      lower physical activity, may contribute to weight gain on an apparent weight
      maintenance diet.

PMID- 25958987
TI  - Placental volume relative to fetal weight estimated by sonography in diabetic
      pregnancies.
AB  - OBJECTIVE: Our purpose was to analyze the fetal weight and placental volume (PV)
      ratio in diabetic pregnancies during mid-pregnancy. METHOD: One hundred and forty
      nine diabetic pregnancies [75 gestational diabetes mellitus (GDM) and 74 diabetes
      mellitus type I (T1DM) with good glycemic control] and 232 healthy patients were
      analyzed by three-dimensional sonographic volumetry of the placenta, while fetal
      weight was estimated by two-dimensional technique. RESULTS: The gestational age
      specific estimated fetal weight (EFW) [EFWGDM: 1840.8 +/- 932.82 g; EFWT1DM:
      1475.6 +/- 914.7 g (mean +/- standard deviation) and placental ratio (PR)] was
      significantly higher (p < 0.05) in pregnancies complicated by GDM and T1DM
      (PRGDM: 5.5 +/- 1.67 g/cm(3), PRT1DM: 4.56 +/- 3.2 g/cm(3)) compared to control
      group (Q) (EFWQ: 532 +/- 186.49 g; PRQ: 2.2 +/- 0.8 g/cm(3)), whereas PV was
      significantly higher (p < 0.05) only in GDM (PVGDM: 334.3 +/- 111.5 cm(3))
      compared to control data (PVQ: 232 +/- 78.9 cm(3)). In contrast to GDM, T1DM with
      good glycemic control did not predispose to any changes in placental sonographic
      volumetric differences compared to control values. CONCLUSIONS: Fetal weight
      related to the PV is already elevated in second trimester in pregnancies
      complicated by gestational diabetes mellitus and type I diabetes mellitus
      compared to normal pregnancies.

PMID- 25958988
TI  - The endometrium from the neonate to the adolescent.
AB  - BACKGROUND: Scientific data on the phenomenon of uterine bleeding in the neonate
      (NUB) began to appear over a century ago when angiogenesis and petechial
      haemorrhages in the endometrium of newborn female infants, as well as fluid blood
      within the uterine cavity, were first described. METHODS: A thorough search of
      the 20th century literature was carried out to identify studies reporting data on
      NUB. RESULTS: The neonatal endometrium, although not identical to the adult,
      shows cellular responses of the same type, and at birth the endometrium is
      proliferative in 2/3 of all newborns with the residual 1/3 showing secretory,
      decidual or menstrual features. In the latter neonates, the presence of a
      functional cervical obstruction may expose them to menstrual regurgitation
      including neonatal mesenchymal stem-like cells. This can represent the origin of
      early-onset endometriosis. At menarche, partial or full ontogenic progesterone
      resistance can occur in the majority. If persisting, adolescent pregnancy may be
      exposed to major obstetrical syndromes including preeclampsia and fetal growth
      restriction. CONCLUSIONS: Increasing evidence indicates that the origin of major
      reproductive disorders in adolescents may lie in the degree of progesterone
      response in the neonate. The spectrum of progesterone response from resistance
      till decidualisation may explain the early occurrence of major obstetrical
      syndromes and endometriosis, respectively.

PMID- 25958990
TI  - Enzymatic Evidence for a Revised Congocidine Biosynthetic Pathway.
AB  - Naturally produced pyrrolamides, such as congocidine, are nonribosomal peptides
      that bind to the minor groove of DNA. Efforts to delineate the biosynthetic
      machinery responsible for their assembly have mainly employed genetic methods,
      and the enzymes responsible for their biosynthesis remain largely
      uncharacterized. We report the biochemical characterization of four proteins
      involved in congocidine formation: the adenylation-thiolation (A-T) di-domain
      Cgc18(1-610), its MbtH-like partner SAMR0548, the AMP-binding enzyme Cgc3*, and
      the T domain Cgc19. We assayed the ATP-dependent activation of various
      commercially available and chemically synthesized compounds with Cgc18(1-610) and
      Cgc3*. We report the revised substrate specificities of Cgc18(1-610) and Cgc3*,
      and loading of 4-acetamidopyrrole-2-carboxylic acid onto Cgc19. Based on these
      biochemical studies, we suggest a revised congocidine biosynthetic pathway. 

PMID- 25958989
TI  - The effect of adopting the IADPSG screening guidelines on the risk profile and
      outcomes of the gestational diabetes population.
AB  - OBJECTIVE: To compare characteristics and outcomes of women diagnosed with
      gestational diabetes mellitus (GDM) by the newer one-step glucose tolerance test
      and those diagnosed with the traditional two-step method. RESEARCH DESIGN AND
      METHODS: This was a retrospective cohort study of women with GDM who delivered in
      2010-2011. Data are reported as proportion or median (interquartile range) and
      were compared using a Chi-square, Fisher's exact or Wilcoxon rank sum test based
      on data type. RESULTS: Of 235 women with GDM, 55.7% were diagnosed using the two
      step method and 44.3% with the one-step method. The groups had similar
      demographics and GDM risk factors. The two-step method group was diagnosed with
      GDM one week later [27.0 (24.0-29.0) weeks versus 26.0 (24.0-28.0 weeks); p =
      0.13]. The groups had similar median weight gain per week before diagnosis. After
      diagnosis, women in the one-step method group had significantly higher median
      weight gain per week [0.67 pounds/week (0.31-1.0) versus 0.56 pounds/week (0.15
      0.89); p = 0.047]. In the one-step method group more women had suspected
      macrosomia (11.7% versus 5.3%, p = 0.07) and more neonates had a birth weight
      >4000 g (13.6% versus 7.5%, p = 0.13); however, these differences were not
      statistically significant. Other pregnancy and neonatal complications were
      similar. CONCLUSIONS: Women diagnosed with the one-step method gained more weight
      per week after GDM diagnosis and had a non-statistically significant increased
      risk for suspected macrosomia. Our data suggest the one-step method identifies
      women with at least equally high risk as the two-step method.

PMID- 25958992
TI  - A mild and efficient CH2-extrusion reaction for the enantiospecific synthesis of
      highly configurationally stable Troger bases.
AB  - A novel CH2 -extrusion reaction leading to the transformation of ethano-Troger
      bases into disubstituted methano derivatives is reported (yields up to 93 %).
      Under mild and metal-free oxidative conditions, a loss of CH2 and a ring
      contraction are provoked. Despite two bond cleavages at stereogenic nitrogen and
      carbon centers and a temporary rupture of the bicyclic structure, a very high
      enantiospecificity (es>=98 %) is observed for this unusual reaction. 

PMID- 25958991
TI  - Cells change their sensitivity to an EGF morphogen gradient to control EGF
      induced gene expression.
AB  - How cells in developing organisms interpret the quantitative information
      contained in morphogen gradients is an open question. Here we address this
      question using a novel integrative approach that combines quantitative
      measurements of morphogen-induced gene expression at single-mRNA resolution with
      mathematical modelling of the induction process. We focus on the induction of
      Notch ligands by the LIN-3/EGF morphogen gradient during vulva induction in
      Caenorhabditis elegans. We show that LIN-3/EGF-induced Notch ligand expression is
      highly dynamic, exhibiting an abrupt transition from low to high expression.
      Similar transitions in Notch ligand expression are observed in two highly
      divergent wild C. elegans isolates. Mathematical modelling and experiments show
      that this transition is driven by a dynamic increase in the sensitivity of the
      induced cells to external LIN-3/EGF. Furthermore, this increase in sensitivity is
      independent of the presence of LIN-3/EGF. Our integrative approach might be
      useful to study induction by morphogen gradients in other systems. 

PMID- 25958993
TI  - High-throughput process development of purification alternatives for the protein
      avidin.
AB  - With an increased number of applications in the field of the avidin-biotin
      technology, the resulting demand for highly-purified protein avidin has drawn our
      attention to the purification process of avidin that naturally occurs in chicken
      egg white. The high-throughput process development (HTPD) methodology was
      exploited, in order to evaluate purification process alternatives to commonly
      used ion-exchange chromatography. In a high-throughput format, process parameters
      for aqueous two-phase extraction, selective precipitation with salts and
      polyethylene glycol, and hydrophobic interaction and mixed-mode column
      chromatography experiments were performed. The HTPD strategy was complemented by
      a high-throughput tandem high-performance liquid chromatography assay for protein
      quantification. Suitable conditions for the separation of avidin from the major
      impurities ovalbumin, ovomucoid, ovotransferrin, and lysozyme were identified in
      the screening experiments. By combination of polyethylene glycol precipitation
      with subsequent resolubilization and separation in a polyethylene
      glycol/sulfate/sodium chloride two-phase system an avidin purity of 77% was
      obtained with a yield >90% while at the same time achieving a significant
      reduction of the process volume. The two-phase extraction and precipitation
      results were largely confirmed in larger scale with scale-up factors of 230 and
      133, respectively. Seamless processing of the avidin enriched bottom phase was
      found feasible by using mixed-mode chromatography. By gradient elution a final
      avidin purity of at least 97% and yield >90% was obtained in the elution pool.
      The presented identification of a new and beneficial alternative for the
      purification of the high value protein thus represents a successful
      implementation of HTPD for an industrially relevant purification task.

PMID- 25958994
TI  - SpONGE: spontaneous organization of numerous-layer generation by electrospray.
AB  - Advanced technologies that can mimic hierarchical architectures found in nature
      can provide pivotal clues for elucidating numerous biological mechanisms. Herein,
      a novel technology, spontaneous organization of numerous-layer generation by
      electrospray (SpONGE), was developed to create self-assembled and multilayered
      fibrous structures. The simple inclusion of salts in a polymer solution prior to
      electrospraying was key to mediating the structural versatilities of the fibrous
      structures. The SpONGE matrix demonstrated great potential as a crucial building
      block capable of inducing sequential, localized drug delivery or orchestrating
      cellular distribution in vivo, thereby expanding its scope of use to cover a
      variety of biomedical applications. 

PMID- 25958995
TI  - Hexacyclopeptides secreted by an endophytic fungus Fusarium solani N06 act as
      crosstalk molecules in Narcissus tazetta.
AB  - The basis of chemical crosstalk in plants and associated endophytes lies in
      certain so-called communication molecules that are responsible for plant-microbe
      and microbe-microbe interactions. Consequently, elucidating the factors that
      affect the nature, distribution, and amount of these molecules and how they
      impact the interaction among endophytes and associated organisms is essential to
      understand the true potential of endophytes. In the present study, we report the
      discovery of nine hexacyclopeptides from an endophytic fungus, Fusarium solani,
      isolated from the bulb of Narcissus tazetta, and their selective accumulation by
      an endophytic bacterium, Achromobacter xylosoxidans isolated from the same
      tissue. We used matrix-assisted laser desorption ionization imaging high
      resolution mass spectrometry (MALDI-imaging-HRMS) to firstly identify and
      visualize the spatial distribution of the hexacyclopeptides produced by
      endophytic F. solani. After culture condition optimization, their sequence was
      identified to be cyclo((Hyp or Dhp)-Xle-Xle-(Ala or Val)-Thr-Xle) (Dhp:
      dehydroproline) by the characteristic a, b, or y ions using liquid chromatography
      tandem mass spectrometry (LC-HRMS(n)). These hexacyclopeptides were confirmed to
      be fungal biosynthetic products by deuterium labeling experiments. Finally, in
      order to understand the plausible ecological relevance of one or more of the
      discovered hexacyclopeptides within the contexts of microbial "neighbor
      communication," we devised a dual-culture setup to visualize using MALDI-imaging
      HRMS how the hexacyclopeptides released by the endophytic fungus are accumulated
      by another endophytic bacterium, A. xylosoxidans, isolated from the same bulb
      tissue. This work exemplifies the relevance of cyclopeptides in endophyte
      endophyte interspecies neighbor communication occurring in nature. Such
      communication strategies are evolved by coexisting endophytes to survive and
      function in their distinct ecological niches. 

PMID- 25958996
TI  - Health for smokers with schizophrenia - a struggle to maintain a dignified life.
AB  - PURPOSE: To investigate the health and lifestyle habits of smokers with
      schizophrenia and describe their experience of smoking in relation to health.
      METHODS: Semi-structured interviews with 10 smokers with schizophrenia were
      conducted in Sweden from May to October 2013. A hermeneutic phenomenological
      approach was used to describe and interpret respondents' experiences. FINDINGS:
      Good health for a person with schizophrenia was defined as accepting their mental
      illness, having strategies to gain control over psychotic symptoms, and engaging
      in activities and good relationships. Lifestyle habits were described as
      structures in the respondents' daily life: arising in the morning, taking a
      cigarette, reading the newspaper, eating breakfast and doing the things planned
      for the day. CONCLUSION: The meaning of health for smokers with schizophrenia is
      not the same as being well or ill. Rather, health is an experience of a struggle
      to maintain a dignified life, including self-acceptance of the mental illness and
      control over the psychotic symptoms. People with schizophrenia have high
      willingness but low motivation to stop smoking because they fear that cigarette
      withdrawal will increase their psychotic symptoms. Therefore, they find it
      difficult to stop smoking. To succeed with health care intervention, health care
      providers must understand the life style habits and experiences specific to
      smokers with schizophrenia and the unique experience of health and life style
      habits that people with schizophrenia experience. IMPLICATIONS FOR
      REHABILITATION: Smokers with schizophrenia experience health as a struggle to
      maintain a dignified life and to maintain control over their psychotic symptoms.
      In smoking cessation programmes, health care providers must pay attention to the
      fear that people with schizophrenia have of losing control over their psychotic
      symptoms, if they stop smoking, and support them to find activities to replace
      smoking. This study suggests that to provide good support in health prevention
      for people with schizophrenia, it is vital for the health care provider to
      understand their unique personal experience of health and life style habits.

PMID- 25958997
TI  - Participation in the workforce after a traumatic brain injury: a matter of
      control.
AB  - PURPOSE: This study sought to explore individual experience in developing a
      mastery of daily activities and roles after a traumatic brain injury (TBI) with
      the objective of returning to work. METHOD: Eight 30-60-year-old men, employed at
      the time of injury, were each interviewed three times over a 6-month period. Ten
      to 21 months after the injuries, four participants had returned to work at least
      part time. Grounded theory was adapted for analyses. RESULTS: A single core
      category emerged: a desire for control: focusing on high-priority issues. Still,
      2 years after injury, the participants were uncertain about their abilities with
      respect to what was expected of them at work. They felt they would do better as
      time progressed. CONCLUSIONS: The participants' uncertainty about their efficacy
      cast doubt on their beliefs in improving their skills, balancing daily activities
      and work. They wondered about the sustainability of their health and efficacy at
      work. Wanting to control their own improvement, the participants asked for
      counselling in strategies and techniques to help with their progress. This issue
      could be taken into account in follow-up rehabilitation programmes. Additionally,
      the workplace might be the ideal context in which to develop the structures and
      routines necessary to master life in general. IMPLICATIONS FOR REHABILITATION:
      Two years after injury, the participants remained uncertain about their abilities
      with respect to what was expected of them at work. The participants felt they
      would do better as time progressed. The participants, wanting to control their
      own improvement, sought counselling to help sort out their priorities and found
      it could contribute to help with their progress in finding a suitable balance
      between daily activities and work. A consequence of our main finding, in a
      multidisciplinary context, is that counselling in structures and routines with
      respect to work-related tasks should be considered to be an integral part of any
      rehabilitation programme after TBI.

PMID- 25958998
TI  - Validity and sensitivity to change of the Patient Specific Functional Scale used
      during rehabilitation following proximal humeral fracture.
AB  - PURPOSE: To describe content validity, concurrent validity, sensitivity to
      change, internal consistency and the outcome distribution of the Patient Specific
      Functional Scale (PSFS) in patients with proximal humeral fracture. METHOD: Fifty
      three patients with proximal humeral fracture treated conservatively or
      surgically with plate and screw or intramedullary nail were recruited 6 weeks (+/
      1 week) post-trauma or post-surgery. The following assessments were used: the
      PSFS, patient global score, shoulder function assessment, grip strength and
      Western Ontario Osteoarthritis of the shoulder Index (WOOS), before start of (n =
      53) and after (n = 22) 2-3 months of group rehabilitation. RESULTS: In total, 96%
      of the activities stated in the PSFS was classified in the International
      Classification of Functioning, Disability and Health activity component and 62%
      were found in the WOOS. Correlations between measures were low. The PSFS was
      highly sensitive to change to a period of group rehabilitation. All questions of
      the PSFS contributed to the total score. Both floor and ceiling effects could be
      noted. CONCLUSION: The PSFS shows satisfying measurement properties and may be a
      useful complement in the evaluation of individual changes during a period of
      rehabilitation after proximal humeral fracture. IMPLICATIONS FOR REHABILITATION:
      The PSFS assesses on activity level in patients with proximal humeral fracture.
      The PSFS is sensitive to change for group rehabilitation after humeral fracture.
      The PSFS can be useful for goal-setting, motivating and individually tailoring
      rehabilitation activities. The PSFS should be used in addition to specific
      measures of body functions and general health.

PMID- 25958999
TI  - Job stability in skilled work and communication ability after moderate-severe
      traumatic brain injury.
AB  - PURPOSE: Communication deficits may play a critical role in maintaining
      employment after traumatic brain injury (TBI), but links between specific
      communication deficits and employment outcomes have not been determined. This
      study identified communication measures that distinguished stably employed versus
      unstably employed adults with TBI. METHODS: Participants were 31 adults with
      moderate-severe TBI who were employed full-time for at least 12 consecutive
      months before injury in skilled jobs and had attempted return to skilled jobs
      after injury. Sixteen had achieved stable employment (SE) post-injury, defined as
      full-time employment for >=12 consecutive months; and 15 had unstable employment
      (UE). Participants completed a battery of communication tests identified in a
      prior qualitative study of communication skills required for skilled work.
      RESULTS: Measures of spoken language comprehension, verbal reasoning, social
      inference, reading and politeness in spoken discourse significantly discriminated
      between SE and UE groups. Two nested models were completed and compared. The
      first model excluded discourse data because of missing data for two UE and one SE
      participant. This model revealed that measures of verbal reasoning speed (beta = 
      0.18, p = 0.05) and social inference (beta = 0.19, p = 0.05) were predictive
      independent of the overall model. The second model included discourse politeness
      data and was a better overall predictor of group membership (Likelihood ratio
      test, Model 1: 3.824, Model 2: 2.865). CONCLUSION: Communication measures were
      positively associated with SE in skilled jobs after TBI. Clinicians should
      include assessment of communication for adults attempting return to work after
      TBI, paying specific attention to social inference and speed of verbal reasoning
      skills. IMPLICATIONS FOR REHABILITATION: Traumatic brain injury (TBI) often
      results in communication impairments associated with the cognitive skills
      underlying interpersonal skills. Communication impairment after TBI has been
      anecdotally associated with job instability. This research associate
      communication functioning with work stability after TBI in skilled jobs. These
      findings indicate that communication impairment should be assessed in persons
      with TBI returning to skilled employment after injury.

PMID- 25959000
TI  - Expert consensus on best evaluative practices in community-based rehabilitation.
AB  - PURPOSE: The objective of this study was to generate expert consensus on best
      evaluative practices for community-based rehabilitation (CBR). This consensus
      includes key features of the evaluation process and methods, and discussion of
      whether a shared framework should be used to report findings and, if so, which
      framework should play this role. METHOD: A Delphi study with two predefined
      rounds was conducted. Experts in CBR from a wide range of geographical areas and
      disciplinary backgrounds were recruited to complete the questionnaires. Both
      quantitative and qualitative analyses were performed to generate the
      recommendations for best practices in CBR evaluation. RESULTS: A panel of 42
      experts reached consensus on 13 recommendations for best evaluative practices in
      CBR. In regard to the critical qualities of sound CBR evaluation processes,
      panellists emphasized that these processes should be inclusive, participatory,
      empowering and respectful of local cultures and languages. The group agreed that
      evaluators should consider the use of mixed methods and participatory tools, and
      should combine indicators from a universal list of CBR indicators with locally
      generated ones. The group also agreed that a common framework should guide CBR
      evaluations, and that this framework should be a flexible combination between the
      CBR Matrix and the CBR Principles. CONCLUSIONS: An expert panel reached consensus
      on key features of best evaluative practices in CBR. Knowledge transfer
      initiatives are now required to develop guidelines, tools and training
      opportunities to facilitate CBR program evaluations. IMPLICATIONS FOR
      REHABILITATION: CBR evaluation processes should strive to be inclusive,
      participatory, empowering and respectful of local cultures and languages. CBR
      evaluators should strongly consider using mixed methods, participatory tools, a
      combination of indicators generated with the local community and with others from
      a bank of CBR indicators. CBR evaluations should be situated within a shared, but
      flexible, framework. This shared framework could combine the CBR Matrix and the
      CBR Principles.

PMID- 25959001
TI  - Genetic association study of coronary collateral circulation in patients with
      coronary artery disease using 22 single nucleotide polymorphisms corresponding to
      10 genes involved in postischemic neovascularization.
AB  - BACKGROUND: Collateral growth in patients with coronary artery disease (CAD) is
      highly heterogeneous. Although multiple factors are thought to play a role in
      collateral development, the contribution of genetic factors to coronary
      collateral circulation (CCC) is largely unknown. The goal of this study was to
      assess whether functional single nucleotide polymorphisms (SNPs) in genes
      involved in vascular growth are associated with CCC. METHODS: 677 consecutive CAD
      patients were enrolled in the study and their CCC was assessed by the Rentrop
      method. 22 SNPs corresponding to 10 genes involved in postischemic
      neovascularization were genotyped and multivariate logistic regression models
      were adjusted using clinically relevant variables to estimate odds ratios and
      used to examine associations of allelic variants, genotypes and haplotypes with
      CCC. RESULTS: Statistical analysis showed that the HIF1A rs11549465 and
      rs2057482; VEGFA rs2010963, rs1570360, rs699947, rs3025039 and rs833061; KDR
      rs1870377, rs2305948 and rs2071559; CCL2 rs1024611, rs1024610, rs2857657 and
      rs2857654; NOS3 rs1799983; ICAM1 rs5498 and rs3093030; TGFB1 rs1800469; CD53
      rs6679497; POSTN rs3829365 and rs1028728; and LGALS2 rs7291467 polymorphisms, as
      well as their haplotype combinations, were not associated with CCC (p < 0.05).
      CONCLUSIONS: We could not validate in our cohort the association of the NOS3
      rs1799983, HIF1A rs11549465, VEGFA rs2010963 and rs699947, and LGALS2 rs7291467
      variants with CCC reported by other authors. A validated SNP-based genome-wide
      association study is required to identify polymorphisms influencing CCC.

PMID- 25959002
TI  - Psychological factors at early stage of treatment as predictors of receiving
      chemotherapy at the end of life.
AB  - INTRODUCTION: Administration of chemotherapy in the last 14 days of life is a
      widely recognized indicator of poor end-of-life (EOL) care. The current study
      aimed to investigate predictors of this outcome, focusing on patients' self
      reported psychological symptoms. METHODS AND MATERIALS: This is a secondary
      analysis of a randomized controlled trial that examined the efficacy of early
      palliative care integrated with standard oncology practice in patients with
      metastatic non-small cell lung cancer (NSCLC). We analyzed associations between
      receipt of chemotherapy within 14 days of death and demographic, clinical, and
      quality-of-life variables in the 125 patients who received chemotherapy in the
      course of their illness and died during the 50-month follow-up. RESULTS: Twenty
      five patients (20%) received chemotherapy within the last 14 days of their life.
      Among demographic and clinical variables, only route of chemotherapy was
      significantly associated with receipt of chemotherapy within 14 days of death
      (oral 34.1% vs. intravenous (i.v.) 12.3%, p < 0.05). In the subsample of
      participants who received i.v. chemotherapy as their last regimen, greater
      anxiety and depression and lower quality of life in emotional, social, and
      existential domains were associated with greater likelihood of receiving
      chemotherapy at the EOL. These associations were not observed in patients who
      received oral chemotherapy as their last regimen. CONCLUSION: Anxiety,
      depression, and worse psychological quality of life at early stage of treatment
      may be associated with the receipt of i.v. chemotherapy at the EOL. Further
      research is needed to examine how these factors might influence decision-making
      about the discontinuation of chemotherapy at the EOL.

PMID- 25959003
TI  - Clonal reproduction shapes evolution in the lizard malaria parasite Plasmodium
      floridense.
AB  - The preponderant clonal evolution hypothesis (PCE) predicts that frequent clonal
      reproduction (sex between two clones) in many pathogens capable of sexual
      recombination results in strong linkage disequilibrium and the presence of
      discrete genetic subdivisions characterized by occasional gene flow. We expand on
      the PCE and predict that higher rates of clonal reproduction will result in: (1)
      morphologically cryptic species that exhibit (2) low within-species variation and
      (3) recent between-species divergence. We tested these predictions in the
      Caribbean lizard malaria parasite Plasmodium floridense using 63 single-infection
      samples in lizards collected from across the parasite's range, and sequenced them
      at two mitochondrial, one apicoplast, and five nuclear genes. We identified 11
      provisionally cryptic species within P. floridense, each of which exhibits low
      intraspecific variation and recent divergence times between species (some
      diverged approximately 110,000 years ago). Our results are consistent with the
      hypothesis that clonal reproduction can profoundly affect diversification of
      species capable of sexual recombination, and suggest that clonal reproduction may
      have led to a large number of unrecognized pathogen species. The factors that may
      influence the rates of clonal reproduction among pathogens are unclear, and we
      discuss how prevalence and virulence may relate to clonal reproduction. 

PMID- 25959004
TI  - Novel therapeutics in the field of capsaicin and pain.
AB  - Capsaicin, a pharmacologically active agent found in chili peppers, causes
      burning and itching sensation due to binding at the transient receptor potential
      vanilloid-1 (TRPV-1) receptor, a polymodal receptor critical to the sensing of a
      variety of stimuli (e.g., noxious heat, bidirectional pH), and subsequent
      activation of polymodal C and A-delta nociceptive fibers. Acutely, TRPV-1
      activation with peripheral capsaicin produces pronociceptive effects, which
      extends to the development of hyperalgesia and allodynia. However, capsaicin has
      been reported to display antinociceptive properties as well, largely through TRPV
      1-dependent mechanisms. Local application of high concentration of capsaicin is
      used for neuropathic pain and repeated stimulation of TRPV-1 induced an
      improvement of epigastric pain in irritable bowel syndrome and dyspepsia patients
      by desensitization of nociceptive pathways. New TRPV-1 agonists are currently
      under preclinical study and TRPV-1 antagonists are in early clinical development
      as analgesics. The TRPV-1 pathway might be a novel target for therapeutics in
      pain sensitivity. 

PMID- 25959005
TI  - Late epidermal growth factor receptor inhibitor-related papulopustular rash: a
      distinct clinical entity.
AB  - We report four patients developing a late form of papulopustular rash induced by
      epidermal growth factor receptor inhibitors. These patients presented an unusual
      presentation of acneiform rash, characterized by late development (several months
      after treatment commenced), localization to the limbs with sparing of the face,
      and association with severe pruritus and Staphylococcus aureus superinfection in
      all cases. These clinical symptoms may suggest a distinct mechanism from the
      early acne-like rash frequently observed with these targeted anticancer
      therapies. Clinicians should be aware of this delayed adverse event, and we
      suggest the term 'late acneiform toxicity of EGFR inhibitors (LATE) syndrome' to
      permit better characterization of this clinical picture. 

PMID- 25959006
TI  - Acute nasal fracture management: A prospective study and literature review.
AB  - OBJECTIVES/HYPOTHESIS: Functional and cosmetic deformities are common after nasal
      injuries and at times necessitate advanced surgery to reverse the effects of
      trauma. This study was designed to study the factors related to nasal injury and
      patient parameters in influencing the acute management of nasal injuries and its
      outcome. STUDY DESIGN: Prospective study. METHODS: Nasal injuries from County
      Waterford in Southeast Ireland were referred to a new Cost-Neutral Nasal Fracture
      Clinic. The first 400 patients from this prospective audit, referred to Waterford
      Regional Hospital from August 2009 through December 2010, were included in this
      study. Twenty-one variables, including satisfaction scores using Visual Analog
      Scale (VAS), were studied. Data was obtained at each stage of management, from
      initial assessment in ears, nose, and throat (ENT) casualty to being seen and
      further reviewed in consultant-based specialty clinic. RESULTS: Men outnumbered
      women 72: 28, and the mean age was 26.89 (0.4 years-87 years). Patients
      presenting time to the ENT casualty after the injury ranged between 1 and 90 days
      (mean 10.5 days). The interval between injury and intervention was on an average
      6.1 days. Accident (41%) and soccer (46%), among the sports group, were
      predominantly related to nasal injury. The overall satisfaction rate was 77.5%
      for breathing and 85.6% for cosmesis. One hundred twenty-seven (31.8%) patients
      were referred to and managed from the septorhinoplasty clinic. Overall, 11%
      required septorhinoplasty. Patient satisfaction was seen in manipulation
      performed up to 5 weeks postinjury. CONCLUSION: Our databank is the largest
      prospectively studied series of nasal-fracture management from Ireland. The
      incidence of nasal fracture in the southeast of Ireland is 0.37%. Age, gender,
      mode of injury, and type of sport influenced the satisfaction rates in this
      study. This type of service may not be practical in all ENT departments, but a
      regional center may be an idea worth considering.

PMID- 25959007
TI  - [Fungiflora Y: A Rapid Test for the Diagnosis of Fungal and Acanthamoeba
      Infections].

PMID- 25959008
TI  - [Sutured Posterior Chamber IOL Fixation in the Absence of Capsular Support, First
      Described in 1954].
AB  - BACKGROUND: By implanting the first IOL in 1949 Ridley's intention was to replace
      the opaque crystalline lens with a "lenticulus" exactly the size and the shape of
      the natural lens in the same physiological location in the posterior chamber.
      Still not resolved at that time was the fixation of the "pseudophakos" following
      intracapsular cataract extraction and the centration on the posterior capsule or,
      respectively, on residues of the anterior capsule following extracapsular
      cataract surgery. We describe the first attempts in 1954 of fixating a posterior
      chamber IOL following intracapsular extraction using a suture technique. MATERIAL
      AND METHODS: Selective literature research via PubMed was undertaken and
      additional literature retrieved by a manual search was included. RESULTS: The
      conventional opinion that suture fixation of intraocular lenses was carried out
      since the 1980s and that Pearce in 1975 and Shearing in 1977 solved this problem
      by using haptics made of polypropylene is not quite correct: In 1954, by using a
      thin wire anchored in the IOL material, the British ophthalmologist, T. G. W.
      Parry, managed the first suture fixation of a Ridley IOL in the posterior
      chamber. CONCLUSIONS: This remarkable medical historical innovation was however
      overshadowed by the rapid development of intraocular lenses, from iris-fixated
      lenses ("collar stud": Epstein 1954, "iris-clip": Binkhorst 1959), anterior
      chamber lenses (Baron 1952, Strampelli 1953) to three-piece lenses for capsular
      bag fixation by Pierce and Shearing in the 1970s. However it becomes obvious that
      already in the 1950s it was possible to correct aphakia in cases with inadequate
      capsular support.

PMID- 25959009
TI  - [Survey of investigation around cases of Rift Valley Fever at Tagant,
      Mauritania].
AB  - BACKGROUND: Rift Valley Fever (RVF) is a zoonotic arbovirosis. Among animals, it
      mainly affects ruminants, causing abortions in gravid females and deaths among
      young animals. In humans, RVF virus infection is usually asymptomatic or
      characterized by a moderate fever. However, in 1-3% of cases, the disease
      progresses to a severe form with 50% mortality. OBJECTIVE: Search for risk
      factors and to propose appropriate measures to prevent the potential for
      extension of the epidemic, and to make recommendations for disease monitoring and
      control. METHODS: This investigation involved human RVF cases reported between
      October 12 and November 20, 2012 in the area of Tagant in Mauritania. Arbovirosis
      diagnosis was established by the laboratory of the National Institute of Public
      Health Research in Nouakchott (Mauritania) in collaboration with the Pasteur
      Institute of Dakar (Senegal). RESULTS: Of 212 subjects, RVF serology was positive
      in 26 (12%). Among those seropositive for RVF, 11 (42%) had severe hemorrhagic
      forms. The case fatality rate was 91%. A series of animal abortions (cattle,
      sheep and goats) was observed in the area where all but two subjects resided.
      Exposure to potential risk factors for RVF virus infection was found in all
      patients. CONCLUSION: Mortality is very high in the hemorrhagic forms of RVF.
      Disease prevention is necessary by strengthening the fight against vectors,
      avoiding contact and consumption of organic products from diseased animals and
      vaccination of animals in areas where the disease is endemic. Furthermore, it is
      essential to establish management procedures for patients infected with the RVF
      virus. An appropriately equipped referral hospital is necessary, together with
      strengthened epidemiological surveillance by notifying all suspected cases of
      hemorrhagic fevers.

PMID- 25959010
TI  - [Should we teach bioethics to students in dentistry as part of public studies? An
      example in the Faculty of Dentistry at the University Paris Descartes].
AB  - BACKGROUND: The dental student is committed to being an actor in public health
      and his/her mission must deal with the wishes of the patient and the ethical
      requirements of the society. In order to improve physical and mental health on an
      individual and collective level, the University has a responsibility to develop a
      real culture of public health early in the academic curriculum. This context
      raises the question of the usefulness of ethics education for students in dental
      school. METHODS: The Faculty of Dentistry at Paris Descartes University is
      engaged in a pilot process to reform dental studies, taking into account official
      and ministerial directives. An educational program on ethics delivered during the
      course of 10 semesters is broken down into lectures, practical lessons, and
      active training in one of four Paris hospitals. RESULTS: Teaching bioethics in
      the public health context puts the student at the center of an active process
      where each student is responsible for personal involvement in five proposed
      teaching methods: lectures, seminars, directed education, and reference research
      using the University's intranet portal. CONCLUSION: The result of 3 years of
      experience teaching bioethics in public health discipline is positive. The dental
      students are encouraged to develop skills to analyze an effective strategy for
      dental care where ethics becomes a cardinal value. In this sense, the teaching of
      bioethics that is at the heart of public debates is perfectly adapted to the
      public health discipline. Ultimately, it could be integrated into the teaching of
      all subjects.

PMID- 25959012
TI  - Synthesis and Nanostructures of Metal Selenide Precursors for Cu(In,Ga)Se2 Thin
      Film Solar Cells.
AB  - A nanoink solution-based process was developed as a low-costing method for the
      fabrication of Cu(In,Ga)Se2 (CIGSe) thin-film photovoltaic cells. The
      sonochemical synthesis of CIGSe nanocrystals of the nanoink through step-by-step
      mixing of the reactants was investigated. To achieve the ideal stoichiometry of
      Cu(In0.7 Ga0.3 )Se2 to tune the bandgap and to fabricate high-efficiency
      photovoltaic cells, the synthetic parameters, the concentration of hydrazine, and
      the amount used of the gallium precursor were investigated. As the hydrazine
      concentration increased, gallium loss was observed in the CIGSe product. The
      gallium content in the reactant mixture strongly affected the metal stoichiometry
      of the prepared CIGSe nanocrystals. The nanoink solution based fabrication of
      thin-film photovoltaic cells was also explored, and the resulting device showed a
      conversion efficiency of 5.17 %. 

PMID- 25959011
TI  - Combination Antisense Treatment for Destructive Exon Skipping of Myostatin and
      Open Reading Frame Rescue of Dystrophin in Neonatal mdx Mice.
AB  - The fatal X-linked Duchenne muscular dystrophy (DMD), characterized by
      progressive muscle wasting and muscle weakness, is caused by mutations within the
      DMD gene. The use of antisense oligonucleotides (AOs) modulating pre-mRNA
      splicing to restore the disrupted dystrophin reading frame, subsequently
      generating a shortened but functional protein has emerged as a potential strategy
      in DMD treatment. AO therapy has recently been applied to induce out-of-frame
      exon skipping of myostatin pre-mRNA, knocking-down expression of myostatin
      protein, and such an approach is suggested to enhance muscle
      hypertrophy/hyperplasia and to reduce muscle necrosis. Within this study, we
      investigated dual exon skipping of dystrophin and myostatin pre-mRNAs using
      phosphorodiamidate morpholino oligomers conjugated with an arginine-rich peptide
      (B-PMOs). Intraperitoneal administration of B-PMOs was performed in neonatal mdx
      males on the day of birth, and at weeks 3 and 6. At week 9, we observed in
      treated mice (as compared to age-matched, saline-injected controls) normalization
      of muscle mass, a recovery in dystrophin expression, and a decrease in muscle
      necrosis, particularly in the diaphragm. Our data provide a proof of concept for
      antisense therapy combining dystrophin restoration and myostatin inhibition for
      the treatment of DMD. 

PMID- 25959013
TI  - Increased intracortical inhibition in elderly adults with anterior-posterior
      current flow: A TMS study.
AB  - OBJECTIVE: All previous studies using TMS to assess short-interval intracortical
      inhibition (SICI) in older adults have used a conventional coil orientation,
      which produces posterior-to-anterior (PA) current flow in the motor cortex.
      However, no studies have examined SICI in older adults by reversing the coil to
      induce anterior-to-posterior (AP) current flow, which is considered more
      sensitive at detecting SICI. Therefore, we investigated age-related changes in
      SICI using both PA and AP TMS across different conditioning stimulus intensities
      and muscle activation states. METHODS: In 22 young and 20 older adults, SICI was
      assessed using PA and AP coil orientations, across a range of conditioning
      stimulus intensities (70-90% active motor threshold), and whilst participants
      kept their first dorsal interosseous (FDI) muscle either relaxed or active (2N
      force). RESULTS: There were no age-related differences in SICI using conventional
      PA TMS in resting or active FDI muscle. However, SICI was increased in elderly
      participants when assessed with reverse coil AP TMS in resting FDI. CONCLUSIONS:
      Coil orientation is a key factor to consider when assessing age-related
      differences in SICI. SIGNIFICANCE: Reverse coil AP TMS can reveal age-related
      changes in SICI, which were previously not evident with conventional PA TMS. This
      may have implications for the assessment of SICI in some clinical populations
      that may show subtle differences in SICI circuitry.

PMID- 25959014
TI  - Reply to "Sural-sparing in Guillain-Barre syndrome: Does it mean lack of
      histopathological changes?".

PMID- 25959015
TI  - Validity of an FFQ assessing the vitamin D intake of young Serbian women living
      in a region without food fortification: the method of triads model.
AB  - OBJECTIVE: The objective of the present study was to examine the external
      validity of an FFQ designed to estimate dietary vitamin D intake compared with a
      plasma biomarker and three repeated 24 h dietary recalls in women of reproductive
      age in Serbia, where there is no exposure to food fortified with vitamin D. The
      method of triads was applied. DESIGN: In a cross-sectional study, 422 women
      completed the Women and Reproductive Health FFQ (WRH-FFQ) during the winter
      months. From a representative subgroup (n 44), three 24 h dietary recalls and
      anthropometric parameters were collected as well as a fasting blood sample for
      vitamin D biomarker analyses. Correlation coefficients were calculated between
      each of the dietary methods. Validity coefficients, as a correlation between the
      measured and estimated 'true' exposure, were calculated using the method of
      triads. Bland-Altman plots were also constructed. SETTING: Three major
      universities in Serbia. SUBJECTS: Healthy young women (n 422) aged 18-35 years.
      RESULTS: The WRH-FFQ estimate of vitamin D intake for all participants was 4.0
      (sd 3.3) ug/d and 3.1 (sd 2.3) ug/d for the subgroup. Bland-Altman plots for
      these intakes showed high agreement. Validity coefficients for the FFQ, 24 h
      recall and biomarker were rho QI=0.847 (95% CI 0.564, 0.928), rho RI=0.810 (95%
      CI 0.537, 0.997) and rho BI=0.499 (95% CI 0.190, 0.840), while the correlation
      coefficients were 0.686, 0.422 and 0.404. CONCLUSIONS: The FFQ applied in the
      present study is a valid tool for assessing dietary vitamin D intake in women
      living in Serbia, a region without mandatory vitamin D food fortification.

PMID- 25959016
TI  - Brightening gold nanoparticles: new sensing approach based on plasmon resonance
      energy transfer.
AB  - Scattering recovered plasmonic resonance energy transfer (SR-PRET) was reported
      by blocking the plasmon resonance energy transfer (PRET) from gold nanoparticle
      (GNP) to the adsorbed molecules (RdBS). Due to the selective cleavage of the Si-O
      bond by F- ions, the quenching is switched off causing an increase in the
      brightness of the GNPs,detected using dark-field microscopy (DFM) were
      brightened. This method was successfully applied to the determination of fluoride
      ions in water. The SR-PRET provides a potential approach for a vitro/vivo sensing
      with high sensitivity and selectivity.

PMID- 25959017
TI  - Renal protective effects of induction of haem oxygenase-1 combined with increased
      adiponectin on the glomerular vascular endothelial growth factor-nitric oxide
      axis in obese rats.
AB  - NEW FINDINGS: What is the central question of this study? This study aimed to
      investigate whether induction of haem oxygenase-1 (HO-1) can protect the kidneys
      of obese rats by regulating the glomerular vascular endothelial growth factor
      nitric oxide (VEGF-NO) axis by increasing the adiponectin concentrations. What is
      the main finding and its importance? Induction of HO-1 reduces the degree of
      microalbuminuria and has renal protective effects by improving endothelial
      function and regulating the uncoupled glomerular VEGF-NO axis in diet-induced
      obese rats. The mechanism may be related to increased activation of the HO-1
      adiponectin axis. The glomerular vascular endothelial growth factor-nitric oxide
      (VEGF-NO) axis plays a critical role in maintenance of normal kidney function in
      obesity. Induction of haem oxygenase-1 (HO-1) may result in a parallel increase
      in adiponectin secretion. The aim of this study was to investigate whether
      induction of HO-1 could protect the kidneys of obese rats by regulating the
      glomerular VEGF-NO axis by increasing adiponectin levels. Rats received high-fat
      diets and were injected with either cobalt protoporphyrin to induce HO-1 or
      stannous protoporphyrin to inhibit HO-1. Blood and urine samples were collected.
      Endothelial function was determined by measuring the endothelium-dependent
      vasodilatation of the aorta. Renal tissues were collected for CD34
      immunohistochemistry. The glomerular VEGF-NO axis and the AMP kinase
      phosphoinositide 3-kinase (PI3K)/Akt-endothelial nitric oxide synthase pathway
      were measured. Induction of HO-1 by cobalt protoporphyrin decreased
      microalbuminuria, plasma free fatty acids, serum high-sensitivity C-reactive
      protein and malondialdehyde levels and increased serum adiponectin levels
      compared with the untreated obese rats. Severe impairment of endothelium
      dependent vasodilatation was observed in the obese rats, which was improved to
      some extent by HO-1 induction. Induction of HO-1 reduced glomerular CD34
      expression and production of reactive oxygen species in obese rats. Obese rats
      showed increased glomerular VEGF expression and reduced NO levels. This
      uncoupling of the glomerular VEGF-NO axis was improved to some extent by
      induction of HO-1, with enhancement of p-AMP kinase, p-Akt and phospho
      endothelial nitric oxide synthase in obese rats. These results indicate that
      induction of HO-1 with cobalt protoporphyrin reduces the degree of
      microalbuminuria and has renal protective effects by improving endothelial
      dysfunction and regulating the glomerular VEGF-NO axis in diet-induced obese rats
      by increasing adiponectin levels.

PMID- 25959018
TI  - Fear of positive evaluation and alcohol use problems among college students: the
      unique impact of drinking motives.
AB  - BACKGROUND AND OBJECTIVES: There is strong empirical support that individuals
      with elevated social anxiety are at risk for alcohol-related impairment. Because
      social anxiety is a multifaceted construct, it is important to consider which
      specific facets contribute to alcohol problem vulnerability. For example,
      although social anxiety has traditionally been conceptualized as a fear of
      negative evaluation (FNE), emerging data suggest that fear of positive evaluation
      (FPE) is also an important factor in pathological social anxiety. The current
      manuscript reports novel findings regarding FPE, alcohol use motives, and
      reported alcohol use problems. DESIGN AND METHODS: Participants included
      undergraduates from two American universities (n = 351) who completed a battery
      of measures assessing fears of evaluation, drinking motives, and alcohol usage
      related problems. RESULTS: FPE significantly predicted alcohol use problems,
      above and beyond FNE. Also, coping and conformity motives for drinking, but not
      social or enhancement motives, each uniquely mediated the relationship between
      FPE and alcohol use problems. CONCLUSIONS: FPE may be an important cognitive
      affective vulnerability factor. With additional clinical research, FPE could
      serve as a meaningful therapeutic target in interventions designed to decrease
      problem drinking among highly socially anxious patients.

PMID- 25959019
TI  - Metabolic engineering in chemolithoautotrophic hosts for the production of fuels
      and chemicals.
AB  - The ability of autotrophic organisms to fix CO2 presents an opportunity to
      utilize this 'greenhouse gas' as an inexpensive substrate for biochemical
      production. Unlike conventional heterotrophic microorganisms that consume
      carbohydrates and amino acids, prokaryotic chemolithoautotrophs have evolved the
      capacity to utilize reduced chemical compounds to fix CO2 and drive metabolic
      processes. The use of chemolithoautotrophic hosts as production platforms has
      been renewed by the prospect of metabolically engineered commodity chemicals and
      fuels. Efforts such as the ARPA-E electrofuels program highlight both the
      potential and obstacles that chemolithoautotrophic biosynthetic platforms
      provide. This review surveys the numerous advances that have been made in
      chemolithoautotrophic metabolic engineering with a focus on hydrogen oxidizing
      bacteria such as the model chemolithoautotrophic organism (Ralstonia), the purple
      photosynthetic bacteria (Rhodobacter), and anaerobic acetogens. Two alternative
      strategies of microbial chassis development are considered: (1) introducing or
      enhancing autotrophic capabilities (carbon fixation, hydrogen utilization) in
      model heterotrophic organisms, or (2) improving tools for pathway engineering
      (transformation methods, promoters, vectors etc.) in native autotrophic
      organisms. Unique characteristics of autotrophic growth as they relate to
      bioreactor design and process development are also discussed in the context of
      challenges and opportunities for genetic manipulation of organisms as production
      platforms. 

PMID- 25959020
TI  - Construction of lycopene-overproducing Saccharomyces cerevisiae by combining
      directed evolution and metabolic engineering.
AB  - Improved supply of farnesyl diphosphate (FPP) is often considered as a typical
      strategy for engineering Saccharomyces cerevisiae towards efficient terpenoid
      production. However, in the engineered strains with enhanced precursor supply,
      the production of the target metabolite is often impeded by insufficient capacity
      of the heterologous terpenoid pathways, which limits further conversion of FPP.
      Here, we tried to assemble an unimpeded biosynthesis pathway by combining
      directed evolution and metabolic engineering in S. cerevisiae for lycopene
      overproduction. First, the catalytic ability of phytoene syntheses from different
      sources was investigated based on lycopene accumulation. Particularly, the
      lycopene cyclase function of the bifunctional enzyme CrtYB from Xanthophyllomyces
      dendrorhous was inactivated by deletion of functional domain and directed
      evolution to obtain mutants with solely phytoene synthase function. Coexpression
      of the resulting CrtYB11M mutant along with the CrtE and CrtI genes from X.
      dendrorhous, and the tHMG1 gene from S. cerevisiae led to production of 4.47 mg/g
      DCW (Dry cell weight) of lycopene and 25.66 mg/g DCW of the by-product squalene.
      To further increase the FPP competitiveness of the lycopene synthesis pathway, we
      tried to enhance the catalytic performance of CrtE by directed evolution and
      created a series of pathway variants by varying the copy number of Crt genes.
      Finally, fed-batch fermentation was conducted for the diploid strain YXWPD-14
      resulting in accumulation of 1.61 g/L (24.41 mg/g DCW) of lycopene, meanwhile,
      the by-production of squalene was reduced to below 1 mg/g DCW.

PMID- 25959021
TI  - Prevalence of sleep disorders among ESRD patients.
AB  - Sleep disorders are common among the patients undergoing dialysis in end stage
      renal disease (ESRD). Although variable, their prevalence has been reported to be
      higher when compared to the general population. The most frequently reported
      complaints are insomnia, restless leg syndrome (RLS), sleep-disordered breathing
      and excessive daytime sleepiness (EDS). The aim of this study was to assess the
      prevalence of sleep disorders in end stage renal disease patients on regular
      hemodialysis (group I with 30 patients) and CKD patients (group II with 30
      patients) in comparison to 30 normal population (control group). In addition to
      laboratory investigations which included creatinine clearance using Cockroft and
      Gault formula, hemoglobin level (Hb), blood urea, serum creatinine, serum
      albumin, serum calcium and phosphorus and lipid profile, all subjects underwent
      one night of laboratory-based polysomnography (PSG) consisting of a standard
      montage of electroencephalography (EEG) (C3/A1 and O2/C3 or O1/C4), monopolar
      left and right electrooculography (EOG) referenced to the opposite mastoid,
      surface mentalis electromyography (EMG), respiratory airflow (measured by
      thermistor) and effort (piezoelectric sensors), electrocardiography (ECG),
      anterior tibialis EMG and pulse oximetry. For hemodialysis subjects, this study
      was performed on a night immediately following hemodialysis treatment. The
      results showed that patients on hemodialysis have sleep disorders, and that sleep
      disorders are common in group I and II than control group. The percentage of
      sleep disorders in hemodialysis patients were as follows: insomnia (69%),
      followed by obstructive sleep apnea syndrome OSAS (24%), RLS and periodic limb
      movement PLM (18%), nightmares (13%), EDS (12%), sleepwalking (2%), possible
      rapid eye movement behavior disorders RED (2%), possible narcolepsy (1.4%). While
      the percentage of sleep disorders in CKD patients were as follows: insomnia
      (54%), followed by RLS (19%), PLM (12%), OSAS (16%), nightmares (15%), EDS (15%),
      sleepwalking (4%), possible RBD (3%), possible narcolepsy (1%). There was inverse
      correlation between sleep disorders and Hb, albumin and creatinine clearance;
      also there was positive correlation between sleep disorder and phosphorus. We
      concluded that the sleep disorders are common in CKD patients either on
      conservative management or on regular hemodialysis. Treatment of anemia,
      hyperphosphatemia and hypoalbuminemia may improve sleep disorders among those
      patients. 

PMID- 25959023
TI  - Tube ileostomy for faecal diversion in elective distal colorectal anastomosis: a
      systematic review and pooled analysis.
AB  - AIM: Tube ileostomy may be an alternative technique to loop ileostomy for
      protection of distal anastomosis, but its evidence base has not yet been
      established. This systematic review aims to evaluate the use of tube ileostomy
      and compare the outcomes associated with it. METHOD: A systematic literature
      search of MEDLINE, EMBASE, Web of Science and the Cochrane database was
      conducted. Studies reporting on elective left-sided/colorectal anastomosis were
      included. Studies which reported on emergent surgery, small bowel anastomosis or
      tube ileostomy as a bridging procedure were excluded. The intra-operative
      technique, postoperative management and complications were assessed. Outcome
      measures included anastomotic leak, reoperation and complications related to the
      stoma or tube ileostomy. RESULTS: Seven studies met the inclusion criteria. Three
      were case series with 101 patients and four were nonrandomized comparative
      studies with 665 patients. Pooled analyses of three comparative studies,
      comparing tube ileostomy (n = 278) with loop ileostomy (n = 254), revealed no
      significant differences in anastomotic leak rates (pooled OR 0.85, 95% CI 0.41
      1.75; I(2) = 0%, P = 0.43). CONCLUSION: There is a re-emergence of interest in
      the use of tube ileostomy to defunction a distal anastomosis. Pooled analyses of
      studies comparing tube ileostomy with loop ileostomy do not show statistically
      significant differences in anastomotic leak rates. Further refinement of this
      technique and randomized controlled studies are necessary for this technique to
      be routinely taken up by surgeons.

PMID- 25959022
TI  - Protective effect of theophylline on renal functions in experimental
      pneumoperitoneum model.
AB  - Our objective in this experimental study is to research the effect of the intra
      abdominal pressure which rises following pneumoperitoneum and whether
      Theophylline has a possible protective activity on this situation. In our study,
      24 Wistar Albino rats were used. Rats were divided into two groups. The first
      group was set for only pneumoperitoneum model. The second group was given 15
      mg/kg of Theophylline intraperitoneally before setting pneumoperitoneum model.
      Then urea, creatinine, cystatin-C, tissue and serum total antioxidant capacity,
      total oxidant capacity and oxidative stress index in two groups were measured and
      compared with each other. Apoptosis and histopathological conditions in the renal
      tissues were examined. The differences between the groups were analyzed with the
      Mann-Whitney U test. Results were considered significant at p < 0.05. No
      statistically significant difference was determined between tissue and serum
      averages in two groups in terms of TAS, TOS and OSI values (p > 0.05). The mean
      value of urea were similar in pneumoperitoneum and pneumoperitoneum +
      theophylline groups (p = 0.12). The mean cystatin-C value was 2.2 +/- 0.3 ug/mL
      in pneumoperitoneum, 1.74 +/- 0.33 ug/mL in pneumoperitoneum + theophylline (p =
      0.002). According to our study, lower cystatin-C levels in the group, where
      Theophylline was given, are suggestive of lower renal injury in this group.
      However, this opinion is interrogated as there is no difference in terms of
      tissue and serum TAS, TOS, OSI and urea values between the groups.

PMID- 25959024
TI  - Molecular cloning and mRNA expression analysis of antizyme inhibitor 1 in the
      ovarian follicles of the Sichuan white goose.
AB  - Antizyme inhibitor 1 (Azin1) plays critical roles in various cellular pathways,
      including ornithine decarboxylase regulation, polyamine anabolism and uptake and
      cell proliferation. However, the molecular characteristics of the AZIN1 gene and
      its expression profile in goose tissues and ovarian follicles have not been
      reported. In this study, the AZIN1 cDNA of the Sichuan white goose (Anser
      cygnoides) was cloned, and analyzed for its phylogenetic and physiochemical
      properties. The expression profile of AZIN1 mRNA in geese tissues and ovarian
      follicles were examined using quantitative real-time PCR. The results showed that
      the open reading frame of the AZIN1 cDNA is 1,353 bp in length, encoding a 450
      amino acid protein with a molecular weight of 50 kDa. Out of all tissues
      examined, AZIN1 expression was highest in the adrenal gland and lowest in breast
      muscle. There was also a high expression of AZIN1 in the cerebellum and isthmus
      of oviduct. With follicular development, AZIN1 gene expression gradually
      increased, and its expression in F1 was significantly higher than in F5 (P<0.05).
      AZIN1 expression was also significantly higher in the POF1 than in the other
      follicles (P<0.05), and there was a low mRNA expression of AZIN1 in atretic
      follicles. The results of AZIN1 expression profiling in ovarian follicles suggest
      that AZIN1 may play an important role in the progression of follicular
      development, potentially through regulating polyamine levels.

PMID- 25959025
TI  - The learning curve for laparoscopic colectomy in colorectal cancer at a new
      regional hospital.
AB  - BACKGROUND: Laparoscopic colorectal surgery has been extensively used, although
      mostly performed in medical centers or university hospitals. We analyzed the
      learning curve of laparoscopic colectomy in a new regional hospital and
      determined the experience necessary to achieve proficiency. METHODS: From July
      2008 to December 2013, the retrospective clinical study enrolled 240 patients who
      underwent laparoscopic colectomy. They were sequentially divided into Group A
      (Patients 1-80), Group B (Patients 81-160), and Group C (Patients 161-240).
      Patient demographics and perioperative parameters were analyzed. Operation time,
      as a measure of learning time, was analyzed using the moving-average method.
      RESULTS: All patients were comparable for age, gender, body mass index, tumor
      location, cancer stage, length of hospital stay, intraoperative complication,
      morbidity, and mortality. Group A experienced more blood loss (p < 0.01) and
      longer operation time (p < 0.001). All laparoscopic operation time stabilized
      after 85 cases. Subgroup analysis showed that operation time stabilized after 15
      cases for right hemicolectomy, 15 cases for sigmoidectomy, and 22 cases for low
      anterior resection with total mesorectal excision. CONCLUSION: Laparoscopic
      colectomy for colorectal cancer in a new regional hospital is feasible and safe.
      It does not need additional time for learning. Laparoscopic sigmoidectomy can be
      considered as the initial surgery for a trainee.

PMID- 25959026
TI  - Biliopancreatic diversion with duodenal switch modifies plasma chemerin in early
      and late post-operative periods.
AB  - OBJECTIVE: Bariatric surgery remains the most effective treatment for obesity and
      metabolic syndrome. Surgical benefit arises from early-phase resolution of
      hyperglycemia and late-phase weight loss. The adipokine chemerin is of interest
      given its roles in immunity, adipogenesis, and metabolism. The study objective
      was to examine the effects of biliopancreatic diversion with duodenal switch (BPD
      DS) on plasma chemerin in the early and late post-operative stages. METHODS: 83
      adults with obesity undergoing BPD-DS, 45 obese non-surgical controls, and 9 lean
      surgical controls were enrolled. Plasma parameters and anthropometric measures
      were obtained at baseline and at, early (24 h, 5 D) and late (6 months and 12
      months) post-operative stages. RESULTS: Plasma chemerin dropped from 176+/-49
      ng/mL at baseline to 132+/-52 ng/mL 24 h after BPD-DS, rebounded to 200+/-66
      ng/mL after 5 D, and declined to 124+/-51 and 110+/-34 ng/mL after 6 and 12
      months. Plasma chemerin correlated negatively with measures of inflammation and
      hepatic injury and positively with measures of obesity, metabolic syndrome, and
      inflammation in the early and late post-operative periods, respectively.
      CONCLUSIONS: Chemerin has a novel role in surgical injury but not hyperglycemia
      resolution early after BPD-DS. Over the long term, plasma chemerin declines to a
      new set point that is partially determined by body fat reductions.

PMID- 25959027
TI  - Familial Mediterranean fever variant with repeated atypical skin eruptions.
AB  - Familial Mediterranean fever (FMF) is characterized by self-limited bouts of
      fever and polyserositis. Skin involvement is not common in FMF, and erysipelas
      like erythema is found to be the most frequent skin eruption which is often
      accompanied by arthritis and fever, and disappears within 12-72 h. We report a 40
      year-old Japanese woman who presented with a 2-year history of recurrent fever
      with general fatigue, polyarthralgia and transient maculopapular eruptions on her
      lower extremities and trunk. The histological findings of the maculopapular
      eruption showed lymphocyte infiltration around the capillaries in the entire
      dermis. Mutation analysis showed a heterozygous E148Q-P369S mutation of MEFV.
      These findings suggested a diagnosis of late-onset FMF variant with atypical skin
      eruptions. The patient was successfully treated with colchicine. Thus, we should
      pay attention to repeated atypical skin eruptions for the early detection of
      atypical FMF. 

PMID- 25959028
TI  - Ameliorative effect of betulinic acid on oxidative damage and apoptosis in the
      splenocytes of dexamethasone treated mice.
AB  - Betulinic acid (BA) is a bioactive pentacyclic triterpene that exhibits a variety
      of biological activities including antioxidative and immunomodulative properties.
      The objective of this study was to investigate the potential splenocytes
      protective effect and underlying mechanism of BA using dexamethasone (Dex)
      induced mice as a model system. Pretreatment with BA (0.25, 0.5, and 1.0 mg/kg)
      dose-dependently ameliorated Dex-induced oxidative damage and apoptosis after 14
      days of feeding. In addition to reactive oxygen species scavenging activity in
      Dex-induced splenocytes, BA administration up-regulated antioxidant enzymes,
      decreased lipid peroxidation, restored mitochondrial function, decreased the
      expression of pro-apoptotic protein Bax, prevented the decline of anti-apoptotic
      protein Bcl-2, inhibited caspase-9 and caspase-3 activation, and improved cell
      survival. These findings reveal that BA was able to mitigate Dex-induced
      oxidative stress and might play an important role in repairs of oxidative damage
      in immunological system.

PMID- 25959029
TI  - Localization of alpha-Dystrobrevin in Cajal Bodies and Nucleoli: A New Role for
      alpha-Dystrobrevin in the Structure/Stability of the Nucleolus.
AB  - alpha-Dystrobrevin (alpha-DB) is a cytoplasmic component of the dystrophin
      associated complex involved in cell signaling; however, its recently revealed
      nuclear localization implies a role for this protein in the nucleus. Consistent
      with this, we demonstrated, in a previous work that alpha-DB1 isoform associates
      with the nuclear lamin to maintain nuclei morphology. In this study, we show the
      distribution of the alpha-DB2 isoform in different subnuclear compartments of
      N1E115 neuronal cells, including nucleoli and Cajal bodies, where it colocalizes
      with B23/nucleophosmin and Nopp140 and with coilin, respectively. Recovery in a
      pure nucleoli fraction undoubtedly confirms the presence of alpha-DB2 in the
      nucleolus. alpha-DB2 redistributes in a similar fashion to that of fibrillarin
      and Nopp140 upon actinomycin-mediated disruption of nucleoli and to that of
      coilin after disorganization of Cajal bodies through ultraviolet-irradiation,
      with relocalization of the proteins to the corresponding reassembled structures
      after cessation of the insults, which implies alpha-DB2 in the plasticity of
      these nuclear bodies. That localization of alpha-DB2 in the nucleolus is
      physiologically relevant is demonstrated by the fact that downregulation of alpha
      DB2 resulted in both altered nucleoli structure and decreased levels of
      B23/nucleophosmin, fibrillarin, and Nopp140. Since alpha-DB2 interacts with
      B23/nucleophosmin and overexpression of the latter protein favors nucleolar
      accumulation of alpha-DB2, it appears that targeting of alpha-DB2 to the
      nucleolus is dependent on B23/nucleophosmin. In conclusion, we show for the first
      time localization of alpha-DB2 in nucleoli and Cajal bodies and provide evidence
      that alpha-DB2 is involved in the structure of nucleoli and might modulate
      nucleolar functions.

PMID- 25959030
TI  - Delineating the spectrum of impairments, disabilities, and rehabilitation needs
      in methylmalonic acidemia (MMA).
AB  - Methylmalonic acidemia patients have complex rehabilitation needs that can be
      targeted to optimize societal independence and quality of life. Thirty-seven
      individuals with isolated MMA (28 mut, 5 cblA, 4 cblB), aged 2-33 years, were
      enrolled in a natural history study, and underwent age-appropriate clinical
      assessments to characterize impairments and disabilities. Neurological
      examination and brain imaging studies were used to document movement disorders
      and the presence of basal ganglia injury. A range of impairments and disabilities
      were identified by a team of physical medicine experts. Movement disorders, such
      as chorea and tremor, were common (n = 31, 83%), even among patients without
      evidence of basal ganglia injury. Joint hypermobility (n = 24, 69%) and pes
      planus (n = 22, 60%) were frequent and, in many cases, under-recognized. 23 (62%)
      patients required gastrostomy feedings. 18/31 patients >4 years old (58%) had
      difficulties with bathing and dressing. 16 of 23 school-aged patients received
      various forms of educational support. Five of the 10 adult patients were employed
      or in college; three lived independently. Unmet needs were identified in access
      to rehabilitation services, such as physical therapy (unavailable to 14/31), and
      orthotics (unavailable to 15/22). We conclude that patients with MMA are
      challenged by a number of functional limitations in essential activities of
      mobility, self-care, and learning, in great part caused by movement disorders and
      ligamentous laxity. Early assessment, referral, and implementation of age
      appropriate rehabilitation services should significantly improve independence and
      quality of life.

PMID- 25959032
TI  - Factors associated with negative histamine control for penicillin allergy skin
      testing in the inpatient setting.
AB  - BACKGROUND: Identification of factors adversely affecting the utility of allergy
      skin testing is important in optimizing patient care. Inpatient penicillin skin
      test data from 1997 through 2007 demonstrate that up to 20% of attempted
      penicillin skin tests are indeterminate owing to a negative histamine test
      response, despite exclusion of H1 antagonists. Critical illness, vasopressors,
      steroid use, and psychotropic medications have been postulated to influence
      outcomes, but large studies are lacking. OBJECTIVE: To identify factors
      associated with a negative histamine test response for the inpatient setting.
      METHODS: Fifty-two cases were identified with a negative histamine response after
      penicillin skin testing in the absence of antihistamine therapy for 72 hours
      before testing. One hundred twenty-five controls with a normal histamine response
      were randomly selected from same population. Independent variables assessed
      included stay in the intensive care unit (ICU), skin color, diabetes, age, use of
      vasopressors, H2 blocker, steroids, other immunosuppressive drugs, thyroid
      replacement, proton pump inhibitors, diuretics, 5 categories of psychotropic
      medications, and amiodarone. RESULTS: Mean age was 68 years for cases vs 60 years
      for controls (P = .002). Bivariate analysis showed ICU stay was more frequent in
      cases than in controls (73.1% vs 33.6%, P < .001). Regression analysis yielded
      odds ratios (ORs) of 8.18 (95% confidence interval 3.22-20.76) for ICU status,
      3.76 (1.30-10.92) for systemic corticosteroids, and 4.90 (1.17-20.62) for H2
      blockers as associated with lack of histamine response. For every additional year
      in age, there was increase in the OR of 1.04 (1.01-1.07). CONCLUSION: Regression
      analysis supports ICU stay during skin testing as associated with a high OR for a
      negative histamine response independent of age. Systemic corticosteroids, H2
      blockers, and older age are associated with a significant OR for a negative
      histamine response. This is one of largest studies on factors associated with a
      negative histamine response for the inpatient setting and has significant
      implications for clinical practice.

PMID- 25959033
TI  - Rhodium(II)-catalyzed enantioselective synthesis of troponoids.
AB  - We report a rhodium(II)-catalyzed highly enantioselective 1,3-dipolar
      cycloaddition reaction between the carbonyl moiety of tropone and carbonyl ylides
      to afford troponoids in good to high yields with excellent enantioselectivity. We
      demonstrate that alpha-diazoketone-derived carbonyl ylides, in contrast to
      carbonyl ylides derived from diazodiketoesters, undergo [6+3] cycloaddition
      reactions with tropone to yield the corresponding bridged heterocycles with
      excellent stereoselectivity. 

PMID- 25959031
TI  - Self-reported physical activity behavior of a multi-ethnic adult population
      within the urban and rural setting in Suriname.
AB  - BACKGROUND: Physical activity (PA) plays an important role in the combat against
      noncommunicable diseases including cardiovascular diseases. In order to develop
      appropriate PA intervention programs, there is a need to evaluate PA behavior. So
      far, there are no published data on PA available for Suriname. Therefore, we aim
      to describe PA behavior among the multi-ethnic population living in urban and
      rural areas of Suriname. METHODS: The World Health Organization (WHO) STEPwise
      approach to chronic disease risk factor surveillance (STEPS) was conducted in a
      national representative sample (N = 5751; 48.6% men) aged 15-64 years between
      March and September 2013. Physical activity data were assessed using the Global
      physical activity questionnaire (GPAQ) and analyzed according to the GPAQ
      guidelines. The prevalence of meeting the recommended PA level and prevalence
      ratios (PR) were computed. RESULTS: Only 55.5% of the overall population met the
      WHO recommended PA levels (urban coastal area: 55.7%, rural coastal area: 57.9%,
      rural interior area: 49.1%). Women were less likely to meet the recommended PA
      level (49% vs 62.4%; p < 0.0001) and with increasing age the PR for recommended
      level of PA decreased (p < 0.0001). Compared to the Hindustani's, the largest
      ethnic group, the Javanese reported the lowest percentage of people meeting
      recommended PA level (PR = 0.92; p = 0.07). CONCLUSION: Around half of the
      population meets the recommended PA level. Future lifestyle interventions aiming
      at increasing PA should especially focus on women and older individuals as they
      are less likely to meet the recommended levels of PA.

PMID- 25959034
TI  - Prediction of nanoparticles-cell association based on corona proteins and
      physicochemical properties.
AB  - Cellular association of nanoparticles (NPs) in biological fluids is affected by
      proteins adsorbed onto the NP surface, forming a "protein corona", thereby
      impacting cellular bioactivity. Here we investigate, based on an extensive gold
      NPs protein corona dataset, the relationships between NP-cell association and
      protein corona fingerprints (PCFs) as well as NP physicochemical properties.
      Accordingly, quantitative structure-activity relationships (QSARs) were developed
      based on both linear and non-linear support vector regression (SVR) models making
      use of a sequential forward floating selection of descriptors. The SVR model with
      only 6 serum proteins and zeta potential had higher accuracy (R(2) = 0.895)
      relative to the linear model (R(2) = 0.850) with 11 PCFs. Considering the initial
      pool of 148 descriptors, the APOB, A1AT, ANT3, and PLMN serum proteins along with
      NP zeta potential were identified as most significant to correlating NP-cell
      association. The present study suggests that QSARs exploration of NP-cell
      association data, considering the role of both NP protein corona and
      physicochemical properties, can support the planning and interpretation of
      toxicity studies and guide the design of NPs for biomedical applications. 

PMID- 25959035
TI  - Acceptability and usability of a telepresence robot for geriatric primary care: A
      pilot.
AB  - The dual challenge of increasing numbers of older adults and overall increases in
      those with some form of insurance is driving the need to develop and evaluate
      novel methods of primary care delivery such as telehealth. The goal of this study
      was to explore the acceptability and usability of a remote presence robot (RPR)
      in a simulated primary care wellness encounter for older adults. A descriptive
      exploratory study was used to determine the acceptability and usability of the
      RPR operated by an APRN 250 miles from 13 older adults residing in a high rise
      during a simulated primary care visit. The results support previous research that
      technology such as the RPR can be both acceptable and useful for an older adult
      and primary care provider but only in certain circumstances. 

PMID- 25959036
TI  - Measuring caregiver activation for health care: Validation of PBH-LCI:D.
AB  - Improving the quality of health care for individuals living with dementia is a
      central goal of the National Alzheimer's Plan, and requires the participation of
      informed family caregivers as active members of the patient's health care team.
      "Caregiver activation" is an emerging concept for which dementia-specific
      measures are lacking. We developed and validated a new self-report index of
      caregiver activation, Partnering for Better Health - Living with Chronic Illness:
      Dementia ( PBH-LCI: D). PBH-LCI: D has high content validity and good internal
      consistency and test-retest reliability, with 32 items and a strong six-factor
      structure reflecting all major health care domains of dementia caregiving.
      Comparisons with measures of related constructs and potential caregiver and
      patient predictors of activation indicate that PBH-LCI: D measures a unique
      construct and therefore should be useful as a marker of caregiver needs for
      education and behavioral change coaching, and as the foundation for developing
      interventions to enhance caregiver activation and successful partnership with
      clinicians.

PMID- 25959038
TI  - The Role of Coping Behavior in Severely Burned Patients With Posttraumatic Stress
      Disorder.
AB  - This multicenter cross-sectional study investigates the role of coping behaviors
      of inpatients with severe burn injuries that determined their development of post
      traumatic stress disorder (PTSD) in burn specialty center in South China. Sixty
      four subjects who were in their rehabilitation period were enrolled in the study.
      Self-report scales, such as the Post-traumatic Stress Disorder Checklist-Civilian
      Version and the Medical Coping Mode Questionnaire, were applied for evaluating
      PTSD symptoms with the severity and classifying coping behaviors. Regression
      analysis evaluated the association of severity of PTSD with coping behaviors.
      Outcomes indicated that coping behaviors could diagnose PTSD symptoms and predict
      the severity of PTSD to some extent. It suggested coping behaviors might
      intermediate the psychological outcomes of the severely burned patients. 

PMID- 25959037
TI  - Evaluation of preintubation shock index and modified shock index as predictors of
      postintubation hypotension and other short-term outcomes.
AB  - PURPOSE: Preintubation shock index (SI) and modified shock index (MSI) have
      demonstrated predictive capability for postintubation hypotension in emergency
      department. The primary aim was to explore this relationship in the critical care
      environment. The secondary aims were to evaluate the relationship of shock
      indices with other short-term outcomes like mortality and length of stay in
      intensive care unit. MATERIALS AND METHODS: This is a nonconcurrent cohort study,
      conducted in eligible 140 adult intensive care unit (ICU) patients of a tertiary
      care medical center. Eligibility criterion was emergent endotracheal intubation
      in apparently hemodynamically stable patients. RESULTS: Preintubation SI >= 0.90
      had a significant association with postintubation hypotension as defined by
      systolic blood pressure < 90 mm Hg in the univariate (P = .03; odds ratio [OR],
      2.13; 95% confidence interval [CI], 1.07-4.35) and multivariate analyses (P =
      .01; OR, 3.17; 95% CI, 1.36-7.73) after adjusting for confounders. It was also
      associated with higher ICU mortality in both the univariate (P = .01; OR, 4.00;
      95% CI, 1.26-12.67) and multivariate analyses (P = .01; OR, 5.75; 95% CI, 1.58
      26.48). There was no association of preintubation MSI with postintubation
      hemodynamic instability and ICU mortality. No association was found between
      preintubation SI and MSI, with ICU length of stay and 30-day mortality.
      CONCLUSIONS: Our findings indicate that preintubation SI greater than or equal to
      0.90 is a predictor of postintubation hypotension (systolic blood pressure <90 mm
      Hg) and ICU mortality in emergently intubated adult patients in intensive care
      units.

PMID- 25959039
TI  - Group Dialectical-Behavior Therapy Skills Training for Conversion Disorder With
      Seizures.
AB  - Neuroimaging evidence suggests deficits in affective regulation in conversion
      disorder (CD). Dialectical-behavior therapy skills training (DBT-ST) was
      developed to target emotion dysregulation. This study was aimed to test the
      feasibility of stand-alone DBT-ST for CD using Linehan's manual for borderline
      personality disorder. In a prospective naturalistic design, 19 adult outpatients
      diagnosed with video EEG-confirmed seizure type CD were recruited and received
      weekly group DBT. Seventeen out of 19 subjects finished an average of 20.5 weeks
      of treatment. The mean seizure rate decreased by 66%. Cessation of seizures
      occurred in 35% of the sample. Completion rates reached 90%. 

PMID- 25959040
TI  - Areas of Brain Damage Underlying Increased Reports of Behavioral Disinhibition.
AB  - Disinhibition, the inability to inhibit inappropriate behavior, is seen in
      frontal-temporal degeneration, Alzheimer's disease, and stroke. Behavioral
      disinhibition leads to social and emotional impairments, including impulsive
      behavior and disregard for social conventions. The authors investigated the
      effects of lesions on behavioral disinhibition measured by the Neuropsychiatric
      Inventory in 177 veterans with traumatic brain injuries. The authors performed
      voxel-based lesion-symptom mapping using MEDx. Damage in the frontal and temporal
      lobes, gyrus rectus, and insula was associated with greater behavioral
      disinhibition, providing further evidence of the frontal lobe's involvement in
      behavioral inhibition and suggesting that these regions are necessary to inhibit
      improper behavior. 

PMID- 25959041
TI  - Inverting papilloma of the temporal bone: Report of four new cases and systematic
      review of the literature.
AB  - OBJECTIVES/HYPOTHESIS: Inverting papillomas (IPs) are benign locally invasive
      tumors that most commonly present within the sinonasal cavity. Temporal bone
      involvement is exceedingly rare, with fewer than 30 cases reported within the
      English literature to date. STUDY DESIGN: Case series and systematic review of
      the literature. METHODS: Four consecutive subjects with temporal bone inverting
      papilloma (TBIP) were treated, and an additional 28 previously published cases
      were identified in the literature. Main outcome measures were disease
      presentation, diagnostic evaluation, management strategy, and outcome. RESULTS: A
      total of 32 cases were analyzed. The median age at diagnosis was 54 years (mean
      54.1; range 19-81 years). Nineteen (59%) patients had synchronous or metachronous
      sinonasal IP, whereas 13 (41%) had isolated temporal bone disease without sinus
      involvement. Over half of the patients undergoing microsurgical resection
      experienced at least one recurrence. Compared to patients with a history of sinus
      IP, subjects with primary TBIP were younger at time of presentation (44 vs. 58
      years; P=0.012); were more commonly female (62% vs. 32%; P=0.15); and were less
      likely to have intracranial spread (8% vs. 26%; P=0.36), cranial neuropathy (8%
      vs. 26%; P=0.36), human papillomavirus positivity (11% vs. 57%; P=0.11), or
      associated carcinoma (0% vs. 47%; P=0.004). CONCLUSIONS: Inverting papilloma of
      the lateral skull base is rare and can pose a significant therapeutic challenge.
      Primary lesions of the temporal bone appear to follow a less aggressive clinical
      course when compared to those arising in association with sinonasal disease.
      Gross total resection is the preferred method of treatment, when feasible, given
      the high rate of recurrence with subtotal resection and risk of associated
      malignancy. LEVEL OF EVIDENCE: 4.

PMID- 25959042
TI  - Antimetastatic effects of gambogic acid are mediated via the actin cytoskeleton
      and NF-kappaB pathways in SK-HEP1 cells.
AB  - Hepatocellular carcinoma (HCC) is one of the most malignant and frequent cancers
      with a high metastatic potential. The prevention of HCC metastasis is a critical
      target for effective therapies in HCC. Gambogic acid (GA), a natural compound
      obtained from Garcinia hanburyi has reported anticancer activity in cell lines.
      However, the antimetastatic mechanisms of GA are unclear, particularly with
      respect to HCC. In this study, the influence of GA on migration and invasion of
      SK-HEP1 cells was evaluated. At concentrations above 0.6 MUM, GA reduced cell
      proliferation in SK-HEP1 cells without affecting proliferation of noncancerous
      HEK-293 cells. GA also suppressed migration and invasion of SK-HEP1 cells. GA
      downregulated the expression of the integrin beta1/rho family GTPase signaling
      pathway, suppressed the actin rearrangement related to cell cytoskeleton and
      migration and decreased matrix metalloproteinases MMP-2, MMP-9, and NF-kappaB
      expression involved in cancer invasion. These results suggest that GA may be a
      potential lead in developing an antimetastatic therapeutic for the treatment of
      HCC.

PMID- 25959043
TI  - Computer-aided analyses of mouse retinal OCT images - an actual application
      report.
AB  - PURPOSE: There is a need for automated retinal optical coherence tomography (OCT)
      image analysis tools for quantitative measurements in small animals. Some image
      processing techniques for retinal layer analysis have been developed, but reports
      about how useful those techniques are in actual animal studies are rare. This
      paper presents the use of a retinal layer detection method we developed in an
      actual mouse study that involves wild type and mutated mice carrying
      photoreceptor degeneration. METHODS: Spectral domain OCT scanning was performed
      by four experimenters over 12 months on 45 mouse eyes that were wild-type,
      deficient for ephrin-A2 and ephrin-A3, deficient for rhodopsin, or deficient for
      rhodopsin, ephrin-A2 and ephrin-A3. The thickness of photoreceptor complex
      between the outer plexiform layer and retinal pigment epithelium was measured on
      two sides of the optic disc as the biomarker of retinal degeneration. All the
      layer detection results were visually confirmed. RESULTS: Overall, 96% (8519 out
      of 9000) of the half-side images were successfully processed using our technique
      in a semi-automatic manner. There was no significant difference in success rate
      between mouse lines (p = 0.91). Based on a human observer's rating of image
      quality for images successfully and unsuccessfully processed, the odds ratios for
      'easily visible' images and 'not clear' images to be successfully processed is 62
      and 4, respectively, against 'indistinguishable' images. Thickness of
      photoreceptor complex was significantly different across the quadrants compared
      (p < 0.001). It was also found that the average thickness based on 4-point sparse
      sampling was not significantly different from the full analysis, while the range
      of differences between the two methods could be up to about 6 MUm or 16% for
      individual eyes. Differences between mouse lines and progressive thickness
      reduction were revealed by both sampling measures. CONCLUSIONS: Although the
      thickness of the photoreceptor complex layer is not even, manual sparse sampling
      may be as sufficiently accurate as full analysis in some studies such as ours,
      where the error of sparse sampling was much smaller than the effect size of
      rhodopsin deficiency. It is also suggested that the image processing method can
      be useful in actual animal studies. Even for images poorly visible to human eyes
      the image processing method still has a good chance to extract the complex layer.

PMID- 25959044
TI  - Tuberculosis infection control measures in diabetes clinics in China: a rapid
      assessment of 10 hospitals.
AB  - OBJECTIVE: To assess tuberculosis infection control measures in diabetes mellitus
      (DM) clinics in China. METHOD: An evaluation questionnaire was developed based on
      the measures outlined in the WHO policy on TB infection control in healthcare
      facilities and congregate settings. Ten selected hospitals were assessed between
      September 2014 and February 2015. RESULTS: All hospitals had an infection control
      committee, an action plan and training, but there was no focus on activities to
      prevent airborne transmission of infection, especially from tuberculosis. All DM
      clinics had natural or artificial ventilation, but at the time of the evaluation
      half had all windows closed. While all the hospitals provided surgical masks for
      hospital staff, none had N95-specific respiratory masks and only three provided
      masks for patients with a cough. There were no policies on identifying DM
      patients with TB symptoms, minimising the time spent by these patients in the
      clinics or developing health educational material on diabetes and tuberculosis.
      CONCLUSION: Infection control measures to prevent airborne transmission in DM
      clinics are inadequate. More work is needed to better understand and determine
      the risk of TB infection in DM clinics and to improve their TB infection control
      practices.

PMID- 25959045
TI  - Ecological evidence that affect and perceptions of drink effects depend on
      alcohol expectancies.
AB  - AIMS: (1) To compare affective changes over drinking and non-drinking days among
      frequent drinkers and (2) to evaluate whether drinkers' expectations influence
      affective changes and perceived pleasure and relief from drinking. DESIGN:
      Observational study involving ecological momentary assessments collected via
      electronic diaries during the course of 3 weeks. SETTING: Drinkers' usual
      settings in Columbia, MO, USA. PARTICIPANTS: A total of 400 adult, frequent
      drinkers, aged 18-70 years. MEASUREMENTS: Ecological assessments included morning
      reports, pre-drinking random prompts, user-initiated first-drink reports and
      device-prompted follow-ups over drinking episodes. Participants rated positive
      (enthusiastic, excited, happy) and negative (distressed, sad) affect and
      perceived pleasure and relief from drinking in real time. A self-report
      questionnaire completed at baseline evaluated expectancies for enhanced
      sociability and tension reduction from drinking. FINDINGS: Relative to affective
      changes over non-drinking days, positive affect increased prior to drinking [95%
      confidence interval (CI) = 0.004, 0.023], and at first drink (95% CI = 0.238,
      0.317), whereas negative affect decreased prior to drinking (95% CI = - 0.007,
      0.000) and at first drink (95% CI = - 0.154, - 0.098). Sociability expectancies
      augmented increases in positive affect prior to drinking (95% CI = 0.009, 0.027)
      and at first drink (95% CI = 0.017, 0.169). Sociability expectancies also
      enhanced perceived pleasure from first drinks (95% CI = 0.046, 0.318). Tension
      reduction expectancies attenuated decreases in negative affect at first drink
      (95% CI = - 0.133, - 0.029), but augmented perceived relief from first drinks
      (95% CI = 0.001, 0.304). CONCLUSIONS: Although theoretical models tend to focus
      on negative affective outcomes of drinking, changes in positive affect prior to
      drinking and early in drinking episodes are important for maintaining drinking
      behavior. Frequent drinkers' expectations for enhanced sociability or tension
      reduction from drinking influence their affective experiences over drinking days
      and perceptions of pleasure and relief from drinking.

PMID- 25959046
TI  - Silver quantum cluster (ag9 )-grafted graphitic carbon nitride nanosheets for
      photocatalytic hydrogen generation and dye degradation.
AB  - We report the visible-light photocatalytic properties of a composite system
      consisting of silver quantum clusters [Ag9 (H2 MSA)7 ] (H2 MSA=mercaptosuccinic
      acid) embedded on graphitic carbon nitride nanosheets (AgQCs-GCN). The composites
      were prepared through a simple chemical route; their structural, chemical,
      morphological, and optical properties were characterized by using X-ray
      diffraction (XRD), energy dispersive X-ray spectroscopy, transmission electron
      microscopy, UV/Vis diffuse reflectance spectroscopy, and photoluminescence
      spectroscopy. Embedment of [Ag9 (H2 MSA)7 ] on graphitic carbon nitride
      nanosheets (GCN) resulted in extended visible-light absorption through multiple
      single-electron transitions in Ag quantum clusters and an effective electronic
      structure for hydroxyl radical generation, which enabled increased activity in
      the photocatalytic degradation of methylene blue and methyl orange dye molecules
      compared with pristine GCN and silver nanoparticle-grafted GCN (AgNPs-GCN).
      Similarly, the amount of hydrogen generated by using AgQCs-GCN was 1.7 times
      higher than pristine GCN. However, the rate of hydrogen generated using AgQCs-GCN
      was slightly less than that of AgNPs-GCN because of surface hydroxyl radical
      formation. The plausible photocatalytic processes are discussed in detail. 

PMID- 25959048
TI  - Continuous minimally invasive cardiac output monitoring with the COstatus in a
      neonatal swine model: recalibration is necessary during vasoconstriction and
      vasodilation.
AB  - BACKGROUND: The COstatus monitor measures cardiac output via the transpulmonary
      ultrasound dilution method (COTPUD ) after injection of normal saline, and can
      calculate continuous cardiac output (CCO) from the arterial pressure waveform.
      The relationship between arterial waveform and COTPUD however, might be degraded
      during vasoconstriction/vasodilation. OBJECTIVES: To examine if recalibration of
      arterial waveform-derived CCO is required during mild
      vasoconstriction/vasodilation. METHODS: In 10 anesthetized piglets (6.6-10.1 kg),
      two COstatus monitors calculated the CCO from the same femoral arterial waveform
      before and during infusions of phenylephrine (PE; 1 or 3 mg.kg(-1) .min(-1) ) and
      sodium nitroprusside (SNP; 1 or 5 mg.kg(-1) .min(-1) ), administered in random
      order. One monitor was recalibrated (CCORecal ) after each intervention, while
      the other monitor was not (CCONon-Recal ). Recalibration was performed with
      COTPUD with 1 ml.kg(-1) normal saline as indicator. The effects of each infusion
      on hemodynamic parameters were compared with baseline using paired t-tests. The
      bias, limits of agreement (LOA), and percentage error between simultaneous
      measurements (CCORecal and CCONon-Recal ) were examined with Bland-Altman plots.
      RESULTS: Infusion of PE significantly increased COTPUD , heart rate (HR), and
      arterial pressures but not systemic vascular resistance (SVR). Infusion of SNP
      decreased arterial pressures without affecting COTPUD , HR, and SVR. There was no
      bias between CCORecal and CCONon-Recal at the baseline, but a small bias was
      observed during PE and SNP infusions. The LOA increased approximately 10 fold
      during vasoconstriction and vasodilation. The percentage error increased from <=
      5% to 32% and 27% during PE and SNP infusions, respectively. CONCLUSION:
      Continuous cardiac output (CO) measured with the COstatus monitor requires
      recalibration during vasoconstriction and vasodilation, even if changes in COTPUD
      or SVR are not substantial.

PMID- 25959047
TI  - Macrophages monitor tissue osmolarity and induce inflammatory response through
      NLRP3 and NLRC4 inflammasome activation.
AB  - Interstitial osmolality is a key homeostatic variable that varies depending on
      the tissue microenvironment. Mammalian cells have effective mechanisms to cope
      with osmotic stress by engaging various adaptation responses. Hyperosmolality due
      to high dietary salt intake has been linked to pathological inflammatory
      conditions. Little is known about the mechanisms of sensing the hyperosmotic
      stress by the innate immune system. Here we report that caspase-1 is activated in
      macrophages under hypertonic conditions. Mice with high dietary salt intake
      display enhanced induction of Th17 response upon immunization, and this effect is
      abolished in caspase-1-deficient mice. Our findings identify an unknown function
      of the inflammasome as a sensor of hyperosmotic stress, which is crucial for the
      induction of inflammatory Th17 response. 

PMID- 25959050
TI  - Thematic analysis of tiles painted by blood and marrow transplant patients during
      treatment.
AB  - The majority of research on understanding the illness focuses on analysing the
      written or verbal content. Thematic analysis of images is a novel qualitative
      approach that can enhance knowledge of the experience of illness. This study used
      thematic analysis to examine 171 tiles painted by patients through the Tiles of
      Hope programme in an outpatient blood and marrow transplant unit. Major themes
      identified in this study were Faith, Hope, Positive Attitude, Nature and Social
      Support. These themes provided a better understanding of patients' perceptions in
      relation to their experience with illness through the art-making process.

PMID- 25959049
TI  - Hepatic steatosis is associated with lower levels of physical activity measured
      via accelerometry.
AB  - OBJECTIVE: Prior studies on the association of physical activity (PA) and
      nonalcoholic fatty liver disease are limited by reliance on subjective measures
      of PA. We examined the association between objectively measured PA and hepatic
      steatosis defined by computed tomography (CT). METHODS: We conducted a cross
      sectional study of 1,060 Framingham Heart Study participants who participated in
      the Multidetector CT 2 substudy and who underwent assessment of PA via
      accelerometry. Hepatic steatosis was estimated by liver attenuation, as measured
      by CT. We explored the relationship between liver attenuation and PA using
      multivariable regression models. RESULTS: In multivariable-adjusted models, we
      observed an inverse association between PA and liver attenuation. Each 30
      minutes/day increase in moderate to vigorous PA (MVPA) was associated with a
      reduced odds of hepatic steatosis (OR = 0.62, P < 0.001). This association was
      attenuated and no longer statistically significant after adjustment for body mass
      index (BMI) (OR = 0.77, P = 0.05) or visceral adipose tissue (VAT) (OR = 0.83, P
      = 0.18). Participants who met the national PA recommendations of engaging in
      >=150 minutes/week of MVPA had the lowest odds of hepatic steatosis, even after
      adjusting for BMI (OR = 0.63, P = 0.007) or VAT (OR = 0.67, P = 0.03).
      CONCLUSIONS: There is an inverse association between PA and hepatic steatosis.
      Participants who met the national PA guidelines had the lowest prevalence of
      hepatic steatosis.

PMID- 25959051
TI  - Human breast cancer invasion and aggression correlates with ECM stiffening and
      immune cell infiltration.
AB  - Tumors are stiff and data suggest that the extracellular matrix stiffening that
      correlates with experimental mammary malignancy drives tumor invasion and
      metastasis. Nevertheless, the relationship between tissue and extracellular
      matrix stiffness and human breast cancer progression and aggression remains
      unclear. We undertook a biophysical and biochemical assessment of stromal
      epithelial interactions in noninvasive, invasive and normal adjacent human breast
      tissue and in breast cancers of increasingly aggressive subtype. Our analysis
      revealed that human breast cancer transformation is accompanied by an incremental
      increase in collagen deposition and a progressive linearization and thickening of
      interstitial collagen. The linearization of collagen was visualized as an overall
      increase in tissue birefringence and was most striking at the invasive front of
      the tumor where the stiffness of the stroma and cellular mechanosignaling were
      the highest. Amongst breast cancer subtypes we found that the stroma at the
      invasive region of the more aggressive Basal-like and Her2 tumor subtypes was the
      most heterogeneous and the stiffest when compared to the less aggressive luminal
      A and B subtypes. Intriguingly, we quantified the greatest number of infiltrating
      macrophages and the highest level of TGF beta signaling within the cells at the
      invasive front. We also established that stroma stiffness and the level of
      cellular TGF beta signaling positively correlated with each other and with the
      number of infiltrating tumor-activated macrophages, which was highest in the more
      aggressive tumor subtypes. These findings indicate that human breast cancer
      progression and aggression, collagen linearization and stromal stiffening are
      linked and implicate tissue inflammation and TGF beta. 

PMID- 25959052
TI  - Long-term results of a concomitant boost radiotherapy technique for elderly
      patients with muscle-invasive bladder cancer.
AB  - OBJECTIVES: To evaluate the long-term clinical efficacy and toxicity of
      concomitant boost radiotherapy (CBRT) in elderly patients with invasive bladder
      cancer. METHODS AND MATERIALS: Elderly patients (n=188; mean 75-year-old, range
      70-91 years; 88.3% male/11.7% female) with T1-T4a bladder carcinoma were
      irradiated with CBRT. A total of 24 (12.8%) patients were diagnosed at stage T1,
      117 (62.2%) were at stage T2, 28 (14.9%) at were stage T3a, 14 (7.4%) were stage
      T3b, and 5 (2.7%) were stage T4a. A dose of 45Gy in 1.8Gy fractions was
      administered to the whole pelvis 5 days/week over 5 weeks. A concomitant boost
      limited to the bladder tumor area plus margin or whole bladder of 22.5Gy in 1.5Gy
      fractions was administered from weeks 3*5. Thus, irradiation totalled 67.5Gy over
      5 weeks. The interfraction interval was >=6h/treatment day. We assessed
      prognostic factors for overall survival (OS), cause-specific survival (CSS) and
      relapse-free survival (RFS). RESULTS: Median follow-up was 46.2 months (range 4.7
      155.7 months). Median overall survival was 27 months (95% CI:21-33 months). In
      this study, 146 (77.7%) patients had complete response, 39 (20.7%) had residual
      disease and 4 (1.6%) had progressive disease. The mean 3-, 5- and 10-year OS
      rates were respectively 41.2% (S.E.+/-0.036), 29% (S.E.+/-0.034), and 13.8%
      (S.E.+/-0.031). Significant prognostic factors for OS and CSS, by multivariate
      analysis, were tumor T-stage and urothelial obstruction. CONCLUSION: This CBRT
      protocol provided excellent results with a high complete response rate and good
      tolerance. This approach may therefore be particularly appropriate for elderly
      patients with invasive bladder cancer.

PMID- 25959053
TI  - Increased expression of the growth-associated protein-43 gene after primary motor
      cortex lesion in macaque monkeys.
AB  - We recently showed that changes of brain activity in the ipsilesional ventral
      premotor cortex (PMv) and perilesional primary motor cortex (M1) of macaque
      monkeys were responsible for recovery of manual dexterity after lesioning M1. To
      investigate whether axonal remodeling is associated with M1 lesion-induced
      changes in brain activity, we assessed gene expression of growth-associated
      protein-43 (GAP-43) in motor and premotor cortices. Increased expression was
      observed in the PMv during the period just after recovery and in the perilesional
      M1 during the plateau phase of recovery. Time-dependent and brain region-specific
      remodeling may play a role in functional recovery after lesioning M1. 

PMID- 25959054
TI  - Placental Volumetry by 2-D Sonography with a New Mathematical Formula:
      Prospective Study on the Shell of a Spherical Sector Model.
AB  - The aim of this study was to determine the utility of a new mathematical model in
      volumetric assessment of the placenta using 2-D ultrasound. Placental volumetry
      was performed in a prospective cross-sectional survey by virtual organ computer
      aided analysis (VOCAL) with the help of a shell-off method in 346 uncomplicated
      pregnancies according to STROBE (Strengthening the Reporting of Observational
      Studies in Epidemiology) guidelines. Furthermore, placental thickness, length and
      height were measured with the 2-D technique to estimate placental volume based on
      the mathematical formula for the volume of "the shell of the spherical sector."
      Fetal size was also assessed by 2-D sonography. The placental volumes measured by
      2-D and 3-D techniques had a correlation of 0.86. In the first trimester, the
      correlation was 0.82, and later during pregnancy, it was 0.86. Placental
      volumetry using "the circle-shaped shell of the spherical sector" mathematical
      model with 2-D ultrasound technique may be introduced into everyday practice to
      screen for placental volume deviations associated with adverse pregnancy outcome.

PMID- 25959055
TI  - Associations between Handgrip Strength and Ultrasound-Measured Muscle Thickness
      of the Hand and Forearm in Young Men and Women.
AB  - It is unknown whether muscle size of intrinsic hand muscles is associated with
      handgrip strength. To investigate the relationships between handgrip strength and
      flexor muscle size of the hand and forearm, muscle thickness (MT) of 86 young
      adults (43 men and 43 women) between the ages of 18 and 34 y was measured by
      ultrasound. Two MTs (forearm radius and forearm ulna MT) in the anterior forearm,
      two MTs (lumbrical and dorsal interosseous MT) in the anterior hand and handgrip
      strength were measured on the right side. Linear regression with part (also
      referred to as semipartial) correlation coefficients revealed that forearm ulna
      MT positively correlated with handgrip strength in both men (part = 0.379, p =
      0.001) and women (part = 0.268, p = 0.002). Dorsal interosseous MT correlated
      with handgrip strength in women only (part = 0.289, p = 0.001). Our results
      suggest that the forearm ulna and dorsal interosseous MTs for women and forearm
      ulna MTs for men are factors contributing to prediction of handgrip strength in
      young adults. 

PMID- 25959056
TI  - Effects of Ultrasound Frequency on Nanodroplet-Mediated Histotripsy.
AB  - Nanodroplet-mediated histotripsy (NMH) is a targeted ultrasound ablation
      technique combining histotripsy with nanodroplets that can be selectively
      delivered to tumor cells for targeted tumor ablation. In a previous study, it was
      reported that by use of extremely short, high-pressure pulses, histotripsy
      cavitation bubbles were generated in regions containing nanodroplets at
      significantly lower pressure (~10.8 MPa) than without nanodroplets (~28 MPa) at
      500 kHz. Furthermore, it was hypothesized that lower frequency would improve the
      effectiveness of NMH by increasing the size of the focal region, increasing
      bubble expansion, and decreasing the cavitation threshold. In this study, we
      investigated the effects of ultrasound frequency (345 kHz, 500 kHz, 1.5 MHz, and
      3 MHz) on NMH. First, the NMH cavitation threshold was measured in tissue
      phantoms with and without nanodroplets, with results indicating that the NMH
      threshold was significantly below the histotripsy intrinsic threshold at all
      frequencies. Results also indicated that the NMH threshold decreased at lower
      frequency, ranging from 7.4 MPa at 345 kHz to 13.2 MPa at 3 MHz. In the second
      part of this study, the effects of frequency on NMH bubble expansion were
      investigated, with results indicating larger expansion at lower frequency, even
      at a lower pressure. In the final part of this study, the ability of
      perfluoropentane-encapsulated nanodroplets to act as sustainable cavitation
      nuclei over multiple pulses was investigated, with results indicating that the
      nanodroplets are destroyed by the cavitation process and only function as
      cavitation nuclei for the first few pulses, with this effect being most
      pronounced at higher frequencies. Overall, the results of this study support our
      hypothesis that using a lower frequency will improve the effectiveness of NMH by
      increasing the size of the focal region, increasing bubble expansion and
      decreasing the cavitation threshold. 

PMID- 25959057
TI  - Effects of Estimators on Ultrasound Nakagami Imaging in Visualizing the Change in
      the Backscattered Statistics from a Rayleigh Distribution to a Pre-Rayleigh
      Distribution.
AB  - Ultrasound Nakagami imaging has recently attracted interest as an imaging
      technique for analyzing envelope statistics. Because the presence of structures
      has a strong effect on estimation of the Nakagami parameter, previous studies
      have indicated that Nakagami imaging should be used specifically for
      characterization of soft tissues with fewer structures, such as liver tissues.
      Typically, changes in the properties of the liver parenchyma cause the
      backscattered statistics to transform from a Rayleigh distribution to a pre
      Rayleigh distribution, and this transformation can be visualized using a Nakagami
      imaging technique. However, different estimators result in different estimated
      values; thus, the performance of a Nakagami image may depend on the type of
      estimator used. This study explored the effects of various estimators on
      ultrasound Nakagami imaging to describe the backscattered statistics as they
      change from a Rayleigh distribution to a pre-Rayleigh distribution. Simulations
      and clinical measurements involving patients with liver fibrosis (n = 85) yielded
      image data that were used to construct B-mode and conventional Nakagami images
      based on the moment estimator (denoted as mINV images) and maximum-likelihood
      estimator (denoted as mML images). In addition, novel window-modulated
      compounding Nakagami images based on the moment estimator (denoted as mWMC
      images) were also obtained. The means and standard deviations of the Nakagami
      parameters were examined as a function of the backscattered statistics. The
      experimental results indicate that the mINV, mML and mWMC images enabled
      quantitative visualization of the change in backscattered statistics from a
      Rayleigh distribution to a pre-Rayleigh distribution. Importantly, the mWMC image
      is superior to both mINV and mML images because it simultaneously realizes
      sensitive detection of the backscattered statistics and a reduction of estimation
      variance for image smoothness improvement. We therefore recommend using mWMC
      image as a novel strategy in Nakagami imaging technique for liver tissue
      characterization. 

PMID- 25959058
TI  - Adjuvant Effect of an Alternative Plasticizer, Diisopropyl Adipate, on a Contact
      Hypersensitivity Mouse Model: Link with Sensory Ion Channel TRPA1 Activation.
AB  - Due to health concerns about phthalate esters, the use of alternative
      plasticizers is being considered. Phthalate esters enhance skin sensitization to
      fluorescein isothiocyanate (FITC) in mouse models. We have demonstrated that
      phthalate esters stimulate transient receptor potential ankyrin 1 (TRPA1) cation
      channels expressed on sensory neurons. We also found a correlation between TRPA1
      activation and the enhancing effect on FITC-induced contact hypersensitivity
      (CHS) when testing various types of phthalate esters. Here we investigated the
      effects of an alternative plasticizer, diisopropyl adipate (DIA). Activation of
      TRPA1 by DIA was demonstrated by calcium mobilization using Chinese hamster ovary
      cells expressing TRPA1 in vitro. The effect of DIA was inhibited by a TRPA1
      specific antagonist, HC-030031. The presence of DIA or dibutyl phthalate (DBP;
      positive control) during skin sensitization of BALB/c mice to FITC augmented the
      CHS response, as revealed by the level of ear-swelling. The enhancing effect of
      DIA was inhibited by in vivo pretreatment with HC-030031. FITC-presenting
      CD11c(+) dendritic cell (DC)-trafficking to draining lymph nodes was facilitated
      both by DIA and by DBP. DBP and DIA were similarly active in the enhancement of
      interferon-gamma production by draining lymph nodes, but the effect on
      interleukin-4 production was weaker with DIA. Overall, DIA activated TRPA1 and
      enhanced FITC-induced CHS, as DBP did. The adjuvant effects of adipate esters may
      need to be considered because they are used as ingredients in cosmetics and drug
      formulations topically applied to the skin. 

PMID- 25959059
TI  - Increased stability of heterogeneous ribonucleoproteins by a deacetylase
      inhibitor.
AB  - Splicing factors are often influenced by various signaling pathways, contributing
      to the dynamic changes of protein isoforms in cells. Heterogeneous
      ribonucleoproteins (hnRNPs) regulate many steps of RNA metabolism including pre
      mRNA splicing but their control by cell signaling particularly through
      acetylation and ubiquitination pathways remains largely unknown. Here we show
      that TSA, a deacetylase inhibitor, reduced the ratio of Bcl-x splice variants Bcl
      xL/xS in MDA-MB-231 breast cancer cells. This TSA effect was independent of
      TGFbeta1; however, only in the presence of TGFbeta1 was TSA able to change the
      splicing regulators hnRNP F/H by slightly reducing their mRNA transcripts but
      strongly preventing protein degradation. The latter was also efficiently
      prevented by lactacystin, a proteasome inhibitor, suggesting their protein
      stability control by both acetylation and ubiquitination pathways. Three lysines
      K87, K98 and K224 of hnRNP F are potential targets of the mutually exclusive
      acetylation or ubiquitination (K(Ac/Ub)) in the protein modification database
      PhosphoSitePlus. Mutating each of them but not a control non-K(Ac/Ub) (K68)
      specifically abolished the TSA enhancement of protein stability. Moreover,
      mutating K98 (K98R) and K224 (K224R) also abolished the TSA regulation of
      alternative splicing of a Bcl-x mini-gene. Furthermore, about 86% (30 of 35) of
      the multi-functional hnRNP proteins in the database contain lysines that are
      potential sites for acetylation/ubiquitination. We demonstrate that the
      degradation of three of them (A1, I and L) are also prevented by TSA. Thus, the
      deacetylase inhibitor TSA enhances hnRNP F stability through the K(Ac/Ub)
      lysines, with some of them essential for its regulation of alternative splicing.
      Such a regulation of protein stability is perhaps common for a group of hnRNPs
      and RNA metabolism. 

PMID- 25959060
TI  - Isoform-level brain expression profiling of the spermidine/spermine N1
      Acetyltransferase1 (SAT1) gene in major depression and suicide.
AB  - Low brain expression of the spermidine/spermine N-1 acetyltransferase (SAT1)
      gene, the rate-limiting enzyme involved in catabolism of polyamines that mediate
      the polyamine stress response (PSR), has been reported in depressed suicides.
      However, it is unknown whether this effect is associated with depression or with
      suicide and whether all or only specific isoforms expressed by SAT1, such as the
      primary 171 amino acid protein-encoding transcript (SSAT), or an alternative
      splice variant (SSATX) that is involved in SAT1 regulated unproductive splicing
      and transcription (RUST), are involved. We applied next generation sequencing
      (RNA-seq) to assess gene-level, isoform-level, and exon-level SAT1 expression
      differences between healthy controls (HC, N = 29), DSM-IV major depressive
      disorder suicides (MDD-S, N = 21) and MDD non-suicides (MDD, N = 9) in the dorsal
      lateral prefrontal cortex (Brodmann Area 9, BA9) of medication-free individuals
      postmortem. Using small RNA-seq, we also examined miRNA species putatively
      involved in SAT1 post-transcriptional regulation. A DSM-IV diagnosis was made by
      structured interview. Toxicology and history ruled out recent psychotropic
      medication. At the gene-level, we found low SAT1 expression in both MDD-S (vs.
      HC, p = 0.002) and MDD (vs. HC, p = 0.002). At the isoform-level, reductions in
      MDD-S (vs. HC) were most pronounced in four transcripts including SSAT and SSATX,
      while reductions in MDD (vs. HC) were pronounced in three transcripts, one of
      which was reduced in MDD relative to MDD-S (all p < 0.1 FDR corrected). We did
      not observe evidence for differential exon-usage (i.e. splicing) nor differences
      in miRNA expression. Results replicate the finding of low SAT1 brain expression
      in depressed suicides in an independent sample and implicate low SAT1 brain
      expression in MDD independent of suicide. Low expressions of both SSAT and SATX
      isoforms suggest that shared transcriptional mechanisms involved in RUST may
      account for low SAT1 brain expression in depressed suicides. Future studies are
      required to understand the functions and regulation of SAT1 isoforms, and how
      they relate to the pathogenesis of MDD and suicide.

PMID- 25959061
TI  - Additive dominant effect of a SOX10 mutation underlies a complex phenotype of
      PCWH.
AB  - Distinct classes of SOX10 mutations result in peripheral demyelinating
      neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and
      Hirschsprung disease, collectively known as PCWH. Meanwhile, SOX10
      haploinsufficiency caused by allelic loss-of-function mutations leads to a milder
      non-neurological disorder, Waardenburg-Hirschsprung disease. The cellular
      pathogenesis of more complex PCWH phenotypes in vivo has not been thoroughly
      understood. To determine the pathogenesis of PCWH, we have established a
      transgenic mouse model. A known PCWH-causing SOX10 mutation, c.1400del12, was
      introduced into mouse Sox10-expressing cells by means of bacterial artificial
      chromosome (BAC) transgenesis. By crossing the multiple transgenic lines, we
      examined the effects produced by various copy numbers of the mutant transgene.
      Within the nervous systems, transgenic mice revealed a delay in the incorporation
      of Schwann cells in the sciatic nerve and the terminal differentiation of
      oligodendrocytes in the spinal cord. Transgenic mice also showed defects in
      melanocytes presenting as neurosensory deafness and abnormal skin pigmentation,
      and a loss of the enteric nervous system. Phenotypes in each lineage were more
      severe in mice carrying higher copy numbers, suggesting a gene dosage effect for
      mutant SOX10. By uncoupling the effects of gain-of-function and
      haploinsufficiency in vivo, we have demonstrated that the effect of a PCWH
      causing SOX10 mutation is solely pathogenic in each SOX10-expressing cellular
      lineage in a dosage-dependent manner. In both the peripheral and central nervous
      systems, the primary consequence of SOX10 mutations is hypomyelination. The
      complex neurological phenotypes in PCWH patients likely result from a combination
      of haploinsufficiency and additive dominant effect. 

PMID- 25959062
TI  - Multiplatform characterization of dynamic changes in breast milk during
      lactation.
AB  - The multicomponent analysis of human breast milk (BM) by metabolic profiling is a
      new area of study applied to determining milk composition, and is capable of
      associating BM composition with maternal characteristics, and subsequent infant
      health outcomes. A multiplatform approach combining HPLC-MS and ultra-performance
      LC-MS, GC-MS, CE-MS, and 1 H NMR spectroscopy was used to comprehensively
      characterize metabolic profiles from seventy BM samples. A total of 710
      metabolites spanning multiple molecular classes were defined. The utility of the
      individual and combined analytical platforms was explored in relation to numbers
      of metabolites identified, as well as the reproducibility of the methods. The
      greatest number of metabolites was identified by the single phase HPLC-MS method,
      while CE-MS uniquely profiled amino acids in detail and NMR was the most
      reproducible, whereas GC-MS targeted volatile compounds and short chain fatty
      acids. Dynamic changes in BM composition were characterized over the first 3
      months of lactation. Metabolites identified as altering in abundance over
      lactation included fucose, di- and triacylglycerols, and short chain fatty acids,
      known to be important for infant immunological, neurological, and
      gastrointestinal development, as well as being an important source of energy.
      This extensive metabolic coverage of the dynamic BM metabolome provides a
      baseline for investigating the impact of maternal characteristics, as well as
      establishing the impact of environmental and dietary factors on the composition
      of BM, with a focus on the downstream health consequences this may have for
      infants.

PMID- 25959064
TI  - Prevalence of celiac disease in Indian patients with irritable bowel syndrome and
      uninvestigated dyspepsia.
AB  - OBJECTIVE: The clinical spectrum of celiac disease (CeD) is wide and its symptoms
      overlap with those of functional bowel diseases. This study aimed to investigate
      the relationship among gluten-related disorders, irritable bowel syndrome (IBS)
      and uninvestigated dyspepsia in Indian patients. METHODS: Patients with IBS and
      uninvestigated dyspepsia (using Rome III criteria) were tested for immunoglobulin
      A (IgA) anti-tissue transglutaminase (anti-tTG) antibody and anti-gliadin
      antibody (AGA). Those with positive anti-tTG antibody were evaluated for the
      presence of villous abnormalities. Patients who were only IgA AGA-positive were
      considered to have gluten sensitivity and those with positive anti-tTG antibody
      and villous atrophy were considered to have CeD. RESULTS: Of 362 patients with
      IBS, 22 (6.1%) had positive anti-tTG antibody, among whom 3 (0.8%) had CeD and 19
      had potential CeD. Of 358 patients with uninvestigated dyspepsia, 18 (5.0%) were
      anti-tTG antibody-positive and among them 4 (1.1%) had CeD and 14 had potential
      CeD. AGA was positive in 104 (28.7%) patients with IBS and 68 (19.0%) with
      uninvestigated dyspepsia, suggesting the presence of gluten sensitivity.
      CONCLUSION: This study highlights the relationship between IBS or dyspepsia and
      CeD or gluten sensitivity.

PMID- 25959063
TI  - IL-10-producing intestinal macrophages prevent excessive antibacterial innate
      immunity by limiting IL-23 synthesis.
AB  - Innate immune responses are regulated in the intestine to prevent excessive
      inflammation. Here we show that a subset of mouse colonic macrophages
      constitutively produce the anti-inflammatory cytokine IL-10. In mice infected
      with Citrobacter rodentium, a model for enteropathogenic Escherichia coli
      infection in humans, these macrophages are required to prevent intestinal
      pathology. IL-23 is significantly increased in infected mice with a myeloid cell
      specific deletion of IL-10, and the addition of IL-10 reduces IL-23 production by
      intestinal macrophages. Furthermore, blockade of IL-23 leads to reduced mortality
      in the context of macrophage IL-10 deficiency. Transcriptome and other analyses
      indicate that IL-10-expressing macrophages receive an autocrine IL-10 signal.
      Interestingly, only transfer of the IL-10 positive macrophages could rescue IL-10
      deficient infected mice. Therefore, these data indicate a pivotal role for
      intestinal macrophages that constitutively produce IL-10, in controlling
      excessive innate immune activation and preventing tissue damage after an acute
      bacterial infection. 

PMID- 25959065
TI  - Detection of (1->3)-beta-D-glucan in same-day urine and serum samples obtained
      from patients with haematological malignancies.
AB  - Serum 1,3-beta-d-glucan (BDG) testing is an established diagnostic marker for
      invasive fungal infections (IFI) among patients with haematological malignancies.
      In contrast limited data exist regarding the application of urine BDG testing.
      Same-day midstream urine and serum screening samples were collected in adult
      patients with underlying haematological malignancies. A total of 80 urine samples
      from 46 patients were investigated: Twenty-six had positive corresponding serum
      BDG >120 pg ml(-1), 27 intermediate (60-80 pg ml(-1)), and 27 negative serum BDG
      (<25 pg ml(-1)). A significant positive correlation between BDG in serum and
      urine samples was observed (P = 0.025; r = 0.252). Sensitivity, specificity,
      positive predictive value and negative predictive value (compared with same-day
      serum results) were: 42%, 76%, 46%, 73% when using an 80 pg ml(-1) urine cut-off,
      and 35%, 96%, 82%, 75% for a 250 pg ml(-1) cut-off. Urine BDG seemed to be higher
      in samples obtained from patients with probable IFI (n = 13, median 145, IQR 22
      253) compared to those from patients without IFI (n = 56, median 24, IQR 15-88)
      but the difference was not significant (P = 0.069). Overall correlation of same
      day urine BDG and serum BDG was moderate. However, urine BDG testing may warrant
      further investigation in larger studies, as high-positive urine results
      correlated with high-positive corresponding serum levels and clinical performance
      was comparable to serum BDG.

PMID- 25959068
TI  - The roles of extracellular related-kinases 1 and 2 signaling in CNS myelination.
AB  - Substantial progress has been made in identifying the intracellular signaling
      pathways that regulate central nervous system myelination. Recently, the mitogen
      activated protein kinase pathway, in particular the extracellular signal-related
      kinase 1 (Erk1) and Erk2, have been identified as critically important in
      mediating the effects of several growth factors that regulate oligodendroglial
      development and myelination. Here we will review the recent studies that identify
      the key role that Erk1/2 signaling plays in regulating oligodendroglial
      development, myelination and remyelination, discuss the potential mechanisms that
      Erk1/2 may utilize to influence myelination, and highlight some questions for
      further research. This article is part of the Special Issue entitled
      'Oligodendrocytes in Health and Disease'.

PMID- 25959066
TI  - Amphetamine sensitization in mice is sufficient to produce both manic- and
      depressive-related behaviors as well as changes in the functional connectivity of
      corticolimbic structures.
AB  - It has been suggested that amphetamine abuse and withdrawal mimics the diverse
      nature of bipolar disorder symptomatology in humans. Here, we determined if a
      single paradigm of amphetamine sensitization would be sufficient to produce both
      manic- and depressive-related behaviors in mice. CD-1 mice were subcutaneously
      dosed for 5 days with 1.8 mg/kg d-amphetamine or vehicle. On days 6-31 of
      withdrawal, amphetamine-sensitized (AS) mice were compared to vehicle-treated
      (VT) mice on a range of behavioral and biochemical endpoints. AS mice
      demonstrated reliable mania- and depression-related behaviors from day 7 to day
      28 of withdrawal. Relative to VT mice, AS mice exhibited long-lasting mania-like
      hyperactivity following either an acute 30-min restraint stress or a low-dose 1
      mg/kg d-amphetamine challenge, which was attenuated by the mood-stabilizers
      lithium and quetiapine. In absence of any challenge, AS mice showed anhedonia
      like decreases in sucrose preference and depression-like impairments in the off
      line consolidation of motor memory, as reflected by the lack of spontaneous
      improvement across days of training on the rotarod. AS mice also demonstrated a
      functional impairment in nest building, an ethologically-relevant activity of
      daily living. Western blot analyses revealed a significant increase in
      methylation of histone 3 at lysine 9 (H3K9), but not lysine 4 (H3K4), in
      hippocampus of AS mice relative to VT mice. In situ hybridization for the
      immediate-early gene activity-regulated cytoskeleton-associated protein (Arc)
      further revealed heightened activation of corticolimbic structures, decreased
      functional connectivity between frontal cortex and striatum, and increased
      functional connectivity between the amygdala and hippocampus of AS mice. The
      effects of amphetamine sensitization were blunted in C57BL/6J mice relative to CD
      1 mice. These results show that a single amphetamine sensitization protocol is
      sufficient to produce behavioral, functional, and biochemical phenotypes in mice
      that are relevant to bipolar disorder.

PMID- 25959069
TI  - Predictors of re-employment: a question of attitude, behavior, or gender?
AB  - This longitudinal study examined the predictive value of attitudes, personal
      related variables, job search behaviour, and demographic variables on re
      employment among 142 assembly workers who had been made redundant. Participants
      completed a questionnaire within a week after leaving their jobs, and another 15
      months later. Results of hierarchical logistic regression revealed that gender
      (being male), was the strongest predictor of re-employment. Willingness to
      relocate and desire to change occupation also increased the odds of re-employment
      15 months after dismissal. On the other hand - having children at home and
      anonymous-passive job-search behaviour, which is more prevalent among women,
      decreased the odds for re-employment. The study is contributing to research by
      revealing gender differences in job search behaviour and the importance of
      focusing qualitative differences instead of merely quantitative measures in job
      search behaviour. And even more important, despite attitude and job-search
      behaviour, there is still differences that seems to be related to gender and
      family responsibility. 

PMID- 25959067
TI  - A novel nicotinic mechanism underlies beta-amyloid-induced neurotoxicity.
AB  - Loss of basal forebrain cholinergic neurons (BFCN) correlates with cognitive
      deficits in Alzheimer disease (AD). Our recent evidence suggests that chronic
      exposure to Abeta up-regulated neuronal alpha7-nAChRs and increased neuronal
      excitability in cultured hippocampal neurons. However, the impact of the up
      regulated alpha7-nAChRs on Abeta-induced neurotoxicity remains unclear. In this
      study, we investigated the role of alpha7-nAChRs in the mediation of Abeta
      induced neurotoxicity. The effects of Abeta exposure on alpha7-nAChRs and
      cytotoxicity were examined using whole-cell patch clamp recordings, atomic force
      microscope (AFM) imaging, immunoprecipitation, and lactate dehydrogenase (LDH)
      release assay in primary cultured hippocampal neurons as well as differentiated
      human neuroblastoma (SH-SY5Y) cells with cholinergic characteristics. We found
      that alpha7-nAChRs are necessary for Abeta-induced neurotoxicity in hippocampal
      neurons because chronic Abeta significantly increased LDH level in hippocampal
      cultures, which was prevented by either alpha7-nAChR antagonist
      methyllycaconitine (MLA) or by alpha7 subunit gene deletion (cultures prepared
      from nAChR alpha7 subunit KO mice), whereas beta2-containing nAChR antagonist
      (dihydro-beta-erythroidine, DhbetaE) or the genetic deletion of nAChR beta2
      subunit (cultures prepared from beta2 KO mice) failed to prevent Abeta-induced
      toxicity. In SH-SY5Y cells, larger aggregates of Abeta preferentially up
      regulated alpha7-nAChR expression and function accompanied by a significant
      decrease in cell viability. Co-treatment MLA, but not mecamylamine (MEC),
      prevented Abeta exposure-induced neurotoxicity. Our results suggest a detrimental
      role of upregulated alpha7-nAChRs in the mediation of Abeta-induced
      neurotoxicity. 

PMID- 25959071
TI  - Study of chemical reactivity in relation to experimental parameters of efficiency
      in coumarin derivatives for dye sensitized solar cells using DFT.
AB  - A group of dyes derived from coumarin was studied, which consisted of nine
      molecules using a very similar manufacturing process of dye sensitized solar
      cells (DSSCs). Optimized geometries, energy levels of the highest occupied
      molecular orbital and the lowest unoccupied molecular orbital, and ultraviolet
      visible spectra were obtained using theoretical calculations, and they were also
      compared with experimental conversion efficiencies of the DSSC. The
      representation of an excited state in terms of natural transition orbitals (NTOs)
      was studied. Chemical reactivity parameters were calculated and correlated with
      the experimental data linked to the efficiency of the DSSC. A new proposal was
      obtained to design new molecular systems and to predict their potential use as a
      dye in DSSCs. 

PMID- 25959070
TI  - Dynamic inclusion complexes of metal nanoparticles inside nanocups.
AB  - Host-guest inclusion complexes are abundant in molecular systems and of
      fundamental importance in living organisms. Realizing a colloidal analogue of a
      molecular dynamic inclusion complex is challenging because inorganic
      nanoparticles (NPs) with a well-defined cavity and portal are difficult to
      synthesize in high yield and with good structural fidelity. Herein, a generic
      strategy towards the fabrication of dynamic 1:1 inclusion complexes of metal
      nanoparticles inside oxide nanocups with high yield (>70%) and regiospecificity
      (>90%) by means of a reactive double Janus nanoparticle intermediate is reported.
      Experimental evidence confirms that the inclusion complexes are formed by a
      kinetically controlled mechanism involving a delicate interplay between bipolar
      galvanic corrosion and alloying-dealloying oxidation. Release of the NP guest
      from the nanocups can be efficiently triggered by an external stimulus.

PMID- 25959072
TI  - Organocatalyzed oxidative N-annulation for diverse and polyfunctionalized
      pyridines.
AB  - This paper describes a novel strategy for the synthesis of 2,3,4-trisubstituted
      pyridines via organocatalyzed three-component reactions. A variety of pyridine
      derivatives are synthesized from readily available ketones with alpha,beta
      unsaturated aldehydes and ammonium acetate under a mild organocatalyst. This
      protocol leads to rapid N-annulation through C-C and C-N bond formation in a
      single operation, thereby avoiding the preparation of essential functional
      groups, such as oximes, imines, or azides. The synthesized compounds are used for
      the evaluation of antibacterial activities and as fluorescence sensors for Cu(2+)
      ions. 

PMID- 25959073
TI  - Dewatering in biological wastewater treatment: A review.
AB  - Biological wastewater treatment removes organic materials, nitrogen, and
      phosphorus from wastewater using microbial biomass (activated sludge, biofilm,
      granules) which is separated from the liquid in a clarifier or by a membrane.
      Part of this biomass (excess sludge) is transported to digesters for bioenergy
      production and then dewatered, it is dewatered directly, often by using belt
      filters or decanter centrifuges before further handling, or it is dewatered by
      sludge mineralization beds. Sludge is generally difficult to dewater, but great
      variations in dewaterability are observed for sludges from different wastewater
      treatment plants as a consequence of differences in plant design and physical
      chemical factors. This review gives an overview of key parameters affecting
      sludge dewatering, i.e. filtration and consolidation. The best dewaterability is
      observed for activated sludge that contains strong, compact flocs without single
      cells and dissolved extracellular polymeric substances. Polyvalent ions such as
      calcium ions improve floc strength and dewaterability, whereas sodium ions (e.g.
      from road salt, sea water intrusion, and industry) reduce dewaterability because
      flocs disintegrate at high conductivity. Dewaterability dramatically decreases at
      high pH due to floc disintegration. Storage under anaerobic conditions lowers
      dewaterability. High shear levels destroy the flocs and reduce dewaterability.
      Thus, pumping and mixing should be gentle and in pipes without sharp bends. 

PMID- 25959074
TI  - Walking Speed: A Summary Indicator of Frailty?

PMID- 25959075
TI  - Sleep Duration and Disturbances Were Associated With Testosterone Level, Muscle
      Mass, and Muscle Strength--A Cross-Sectional Study in 1274 Older Men.
AB  - BACKGROUND: Testosterone level follows a circadian rhythm. However, whether sleep
      duration and disturbances can affect testosterone level, muscle mass, and
      strength remains unknown. OBJECTIVE: To examine the relationship of sleep
      duration and disturbances to testosterone level, muscle mass, muscle strength,
      and walking speed. PARTICIPANTS AND METHODS: We recruited 1274 community-dwelling
      men older than 65 years of age. Their early morning testosterone level was
      assayed by mass spectrometry. A sleep questionnaire was administered to enquire
      about their reported sleep duration, prolonged sleep latency (>0.5 hour), and
      subjective insomnia complaint. Muscle mass was measured by dual-energy x-ray
      absorptiometry. Testosterone level, muscle mass, handgrip strength, and walking
      speed were tested against sleep duration and disturbances. RESULTS: Testosterone
      increased with increasing sleep duration up to 9.9 hours, after which it
      decreased, giving rise to an inverted U-shaped relationship (P for quadratic
      trend <.05). A similar inverted U-shaped relationship occurred between sleep
      duration and muscle mass and function. Earlier go-to-bed time, despite being
      associated with a higher testosterone level (P < .05), was associated with weaker
      grip strength (P < .05). Earlier wake-up time was associated with higher muscle
      mass (P < .05) but neither grip strength nor walking speed. Neither prolonged
      sleep latency nor insomnia was associated with testosterone levels. However,
      prolonged sleep latency was associated with lower muscle mass (P < .05), weaker
      grip strength (P < .05), and slower walking speed (P < .001). Insomnia, on the
      other hand was associated with weaker grip strength (P < .05) and slower walking
      speed (P < .001) but not muscle mass. CONCLUSIONS: Sleep duration and
      disturbances can affect testosterone level, muscle mass, and its function.
      Whether optimization of sleep can ameliorate age-associated decline in sex
      hormone and muscle performance warrants further studies.

PMID- 25959076
TI  - Kinetic Evaluation of Determinant Factors for Cellular Accumulation of
      Protoporphyrin IX Induced by External 5-Aminolevulinic Acid for Photodynamic
      Cancer Therapy.
AB  - Five-aminolevulinic acid (ALA) is a prodrug to generate phototoxic protoporphyrin
      IX (PPIX) for photodynamic cancer therapy. It remains unclear how PPIX
      accumulates in cancer cells; therefore, we aimed to clarify determinant factors
      by assessing ALA uptake, PPIX biosynthesis, conversion of PPIX to heme
      (ferrochelatase activity), and PPIX efflux, independently, in 10 human cancer
      cell lines. ALA-induced PPIX accumulation was not correlated with ALA uptake
      clearance. ALA uptake rates were far greater than maximum conversion rates of ALA
      to PPIX in the five cell lines, where ALA uptake activity was detected. A
      negative correlation of PPIX accumulation with ferrochelatase activity was found,
      but not statistically significant among all cell lines. As PPIX accumulation was
      restored in MCF-7 and DU145 cells by adding an inhibitor of PPIX efflux
      transporter BCRP, a compartment model incorporating PPIX synthesis,
      ferrochelatase activity, and PPIX efflux, was established, and hybrid parameters
      (pi index) calculated using the model were significantly correlated with ALA
      induced PPIX accumulation (r = 0.90, p = 0.005). Accordingly, kinetic analyses
      indicate that ALA-induced PPIX levels are determined by the three processes of
      PPIX biosynthesis, conversion of PPIX to heme, and PPIX efflux, suggesting that
      pi index is a useful to predict ALA-induced PPIX accumulation.

PMID- 25959077
TI  - Environmentally Friendly Carbon-Preserving Recovery of Noble Metals From
      Supported Fuel Cell Catalysts.
AB  - The dissolution of noble-metal catalysts under mild and carbon-preserving
      conditions offers the possibility of in situ regeneration of the catalyst
      nanoparticles in fuel cells or other applications. Here, we report on the
      complete dissolution of the fuel cell catalyst, platinum nanoparticles, under
      very mild conditions at room temperature in 0.1 M HClO4 and 0.1 M HCl by
      electrochemical potential cycling between 0.5-1.1 V at a scan rate of 50 mV s(-1)
      . Dissolution rates as high as 22.5 MUg cm(-2) per cycle were achieved, which
      ensured a relatively short dissolution timescale of 3-5 h for a Pt loading of
      0.35 mg cm(-2) on carbon. The influence of chloride ions and oxygen in the
      electrolyte on the dissolution was investigated, and a dissolution mechanism is
      proposed on the basis of the experimental observations and available literature
      results. During the dissolution process, the corrosion of the carbon support was
      minimal, as observed by X-ray photoelectron spectroscopy (XPS).

PMID- 25959079
TI  - Studies on tridecaptin B(1), a lipopeptide with activity against multidrug
      resistant Gram-negative bacteria.
AB  - Previously other groups had reported that Paenibacillus polymyxa NRRL B-30507
      produces SRCAM 37, a type IIA bacteriocin with antimicrobial activity against
      Campylobacter jejuni. Genome sequencing and isolation of antimicrobial compounds
      from this P. polymyxa strain show that the antimicrobial activity is due to
      polymyxins and tridecaptin B1. The complete structural assignment, synthesis, and
      antimicrobial profile of tridecaptin B1 is reported, as well as the putative gene
      cluster responsible for its biosynthesis. This peptide displays strong activity
      against multidrug resistant Gram-negative bacteria, a finding that is timely to
      the current problem of antibiotic resistance. 

PMID- 25959078
TI  - Reconstruction algorithm for nasal basal cell carcinoma with skin involvement
      only: analysis of 221 cases repaired by minor surgery.
AB  - BACKGROUND: Basal cell carcinoma (BCC) often occurs on the nose. Reconstruction
      of the nose should yield excellent aesthetic and functional outcomes. AIM: We
      propose a technical algorithm for the reconstruction of surgical defects, based
      on our analysis of 221 cases of nasal BCC with skin involvement only, which could
      be repaired by minor surgery. METHODS: The aesthetic and functional outcomes for
      various reconstruction techniques were analysed according to defect location and
      size. A reconstruction algorithm was proposed with the aim of obtaining the best
      surgical results. RESULTS: Defect location and size were key considerations.
      Primary closure was the first option for small defects (< 10 mm), with scores of
      3.4 for objective aesthetic outcome (OAO), 3.2 for subjective aesthetic outcome
      (SAO) and 3.3 for subjective functional outcome (SFO). The first option for
      medium defects (1-20 mm) was the island pedicle flap, with scores of 3.5 for OAO,
      3.2 for SAO and 3.7 for SFO. The first option for large defects (> 20 mm) was the
      transposition flap for the upper nose (scores of 2.0 for OAO and SAO and 3.0 for
      SFO) and the interpolation flap for the lower nose (2.8 for OAO and 2.9 for SAO
      and SFO). CONCLUSIONS: We have proposed an algorithm to select the optimal
      technique for repairing nasal BCC surgical defects according to their size and
      location.

PMID- 25959080
TI  - Pd-catalyzed carbonylative cycloamidation of ketoimines for the synthesis of
      pyrido[1,2-a]pyrimidin-4-ones.
AB  - The Pd(ii)-catalyzed pyridine-directed carbonylative cycloamidation of ketoimines
      has provided an efficient protocol for assembly of pyrido[1,2-a]pyrimidin-4-ones.

PMID- 25959085
TI  - SCD1 inhibition during 3T3-L1 adipocyte differentiation remodels triacylglycerol,
      diacylglycerol and phospholipid fatty acid composition.
AB  - The conversion of saturated fatty acids (FAs) palmitate (16:0) and stearate
      (18:0) into monounsaturated FAs palmitoleate (16:1n-7) and oleate (18:1n-9) is
      catalyzed by stearoyl-CoA desaturase 1 (SCD1). These FAs represent the dominant
      constituents of adipocyte triacylglycerols (TAGs) and phospholipids (PLs). Given
      the critical role of SCD1 in lipid metabolism and the notable increase in its
      expression during adipogenesis, reductions in SCD1 activity have the potential to
      compromise the adipocyte's ability to accumulate lipid. The current study used
      thin-layer and gas chromatography to examine the content and FA composition of
      TAGs, PLs, cholesteryl esters, diacylglycerols and free fatty acids in SCD1
      inhibited differentiating 3T3-L1 adipocyte cells. SCD1 inhibition reduced total
      cellular PL and TAG content concurrent with the down-regulation of genes involved
      in TAG and PL biosynthesis; however, the relative amount of PL was unaltered.
      While total DAG levels were increased ~2.7-fold in SCD1-inhibited adipocytes,
      this did not induce JNK activation; however, phosphorylated (Ser473) AKT was
      significantly reduced. As expected, total SFA and MUFA content were increased
      (~1.3-fold) and decreased (~4.0-fold). Further, SCD1 inhibition caused a ~2.2
      fold increase and a ~8.3-fold decrease in total cellular 18:0 and 16:1n-7 levels,
      respectively. Similar changes were also seen in other lipid fractions. The levels
      of other FAs, including polyunsaturated FAs, were also changed in SCD1-inhibited
      adipocytes. Together, these results add to the existing body of knowledge
      regarding SCD1 function in adipocytes and highlight its important role in
      regulating global adipocyte lipid composition. 

PMID- 25959086
TI  - A method for determining delta-aminolevulinic acid synthase activity in
      homogenized cells and tissues.
AB  - OBJECTIVE: In mammalian cells the rate-limiting step in heme biosynthesis is the
      formation of delta-aminolevulinic acid (ALA). The reaction intermediates,
      porphyrins and iron and the final product, heme can be highly cytotoxic if
      allowed to accumulate. The importance of maintaining the levels of metabolic
      intermediates and heme within a narrow range is apparent based on the complex
      homeostatic system(s) that have developed. Ultimately, determining the enzymatic
      activity of ALA synthase (ALAS) present in the mitochondria is highly beneficial
      to confirm the effects of the transcriptional, translational and post
      translational events. The aim of this study was to develop a highly sensitive
      assay for ALAS that could be used on whole tissue or cellular homogenates. DESIGN
      AND METHODS: A systematic approach was used to optimize steps in formation of ALA
      by ALAS. Reducing the signal to noise ratio for the assay was achieved by
      derivatizing the ALA formed into a fluorescent product that could be efficiently
      separated by ultra performance liquid chromatography (UPLC) from other
      derivatized primary amines. The stability of ALAS activity in whole tissue
      homogenate and cellular homogenate was determined after extended storage at -80 
      degrees C. CONCLUSIONS: A method for assaying ALAS has been developed that can be
      used with tissue homogenates or cellular lysates. There is no need to purify
      mitochondria and radiolabeled substrates are not needed for this assay. General
      laboratory reagents can be used to prepare the samples. Standard UPLC
      chromatography will resolve the derivatized ALA peak. Samples of tissue
      homogenate can be stored for approximately one year without significant loss of
      enzymatic activity.

PMID- 25959087
TI  - Phosphoproteomic analysis of wild-type and antimony-resistant Leishmania
      braziliensis lines by 2D-DIGE technology.
AB  - Protein phosphorylation is one of the most studied post-translational
      modifications that is involved in different cellular events in Leishmania. In
      this study, we performed a comparative phosphoproteomics analysis of potassium
      antimonyl tartrate (SbIII)-resistant and -susceptible lines of Leishmania
      braziliensis using a 2D-DIGE approach followed by MS. In order to investigate the
      differential phosphoprotein abundance associated with the drug-induced stress
      response and SbIII-resistance mechanisms, we compared nontreated and SbIII
      treated samples of each line. Pair wise comparisons revealed a total of 116 spots
      that showed a statistically significant difference in phosphoprotein abundance,
      including 11 and 34 spots specifically correlated with drug treatment and
      resistance, respectively. We identified 48 different proteins distributed into
      seven biological process categories. The category "protein folding/chaperones and
      stress response" is mainly implicated in response to SbIII treatment, while the
      categories "antioxidant/detoxification," "metabolic process," "RNA/DNA
      processing," and "protein biosynthesis" are modulated in the case of antimony
      resistance. Multiple sequence alignments were performed to validate the
      conservation of phosphorylated residues in nine proteins identified here. Western
      blot assays were carried out to validate the quantitative phosphoproteome
      analysis. The results revealed differential expression level of three
      phosphoproteins in the lines analyzed. This novel study allowed us to profile the
      L. braziliensis phosphoproteome, identifying several potential candidates for
      biochemical or signaling networks associated with antimony resistance phenotype
      in this parasite. 

PMID- 25959088
TI  - Malposition of hemodialysis catheter in left superior intercostal vein.
AB  - Malposition of hemodialysis catheter needs to be identified promptly. Straight
      descent of left side internal jugular catheter mandates a thorough evaluation
      than unnecessary apprehensions. We report an unusual case of straight descent of
      hemodialysis catheter into superior intercostal vein. 

PMID- 25959089
TI  - Treatment of unresponsive hypoparathyroidism when the oral route administration
      is not possible: considering subcutaneous teriparatide.

PMID- 25959090
TI  - A study of the relationship between water and anions of the Hofmeister series
      using pressure perturbation calorimetry.
AB  - Pressure perturbation calorimetry (PPC) was used to study the relationship
      between water and sodium salts with a range of different anions. At temperatures
      around 25  degrees C the heat on pressurisation (DeltaQ) from 1 to 5 bar was
      negative for all solutions relative to pure water. The raw data showed that as
      the temperature rose, the gradient was positive relative to pure water and the
      transition temperature where DeltaQ was zero was related to anion surface charge
      density and was more pronounced for the low-charge density anions. A three
      component model was developed comprising bulk water, the hydration layer and the
      solute to calculate the molar expansivity of the hydration layer around the ions
      in solution. The calculated molar expansivities of water in the hydration layer
      around the ions were consistently less than pure water. DeltaQ at different
      disodium hydrogen phosphate concentrations showed that the change in molar
      enthalpy relative to pure water was not linear even as it approached infinite
      dilution suggesting that while hydration layers can be allocated to the water
      around ions this does not rule out interactions between water and ions extending
      beyond the immediate hydration layer. 

PMID- 25959092
TI  - Seasonal recharge and mean residence times of soil and epikarst water in a small
      karst catchment of southwest China.
AB  - Soil and epikarst play an important role in the hydrological cycle in karst
      regions. This paper focuses on investigating the seasonal recharge and mean
      residence time (MRT) of soil water and epikarst water in a small karst catchment
      of southwest China. The deuterium contents in precipitation, creek, soil baseflow
      (direct recharge of the saturated soil water to the stream), epikarst spring, and
      soil waters were monitored weekly for two years, and MRT was calculated by an
      exponential model (EM) and a dispersion model (DM). The obvious seasonal
      variation of deuterium in rainfall was buffered in epikarst water, indicating
      sufficient water mixing. Soil baseflow contained less rainy-season rainwater than
      epikarst spring discharge, reflecting the retarded effect of soil thickness on
      rainwater recharge. MRTs of all water bodies were 41-71 weeks, and soils in the
      depression extended those of shallow groundwater. This demonstrated that the deep
      soil layer played an important role in karst hydrological processes in the study
      catchment. The creek was recharged mostly by rainfall through epikarst,
      indicating its crucial role in water circulation. These results showed epikarst
      had a strong water-holding capacity and also delayed water contact time with
      dolomite. 

PMID- 25959091
TI  - Autologous cellular vaccine overcomes cancer immunoediting in a mouse model of
      myeloma.
AB  - In the Sp6 mouse plasmacytoma model, a whole-cell vaccination with Sp6 cells
      expressing de novo B7-1 (Sp6/B7) induced anatomically localized and cytotoxic T
      cell (CTL)-mediated protection against wild-type (WT) Sp6. Both WT Sp6 and Sp6/B7
      showed down-regulated expression of MHC H-2 L(d). Increase of H-2 L(d) expression
      by cDNA transfection (Sp6/B7/L(d)) raised tumour immune protection and shifted
      most CTL responses towards H-2 L(d)-restricted antigenic epitopes. The tumour
      protective responses were not specific for the H-2 L(d)-restricted immunodominant
      AH1 epitope of the gp70 common mouse tumour antigen, although WT Sp6 and
      transfectants were able to present it to specific T cells in vitro. Gp70
      transcripts, absent in secondary lymphoid organs of naive mice, were detected in
      immunized mice as well as in splenocytes from naive mice incubated in vitro with
      supernatants of CTL-lysed Sp6 cell cultures, containing damage-associated
      molecular patterns (DAMPs). It has been shown that Toll-like receptor triggering
      induces gp70 expression. Damage-associated molecular patterns are released by CTL
      mediated killing of Sp6/B7-Sp6/B7/L(d) cells migrated to draining lymph nodes
      during immunization and may activate gp70 expression and presentation in most
      resident antigen-presenting cells. The same could also apply for Mus musculus
      endogenous ecotropic murine leukaemia virus 1 particles present in Sp6-cytosol,
      discharged by dying cells and superinfecting antigen-presenting cells. The
      outcome of such a massive gp70 cross-presentation would probably be tolerogenic
      for the high-affinity AH1-gp70-specific CTL clones. In this scenario, autologous
      whole-tumour-cell vaccines rescue tumour-specific immunoprotection by
      amplification of subdominant tumour antigen responses when those against the
      immune dominant antigens are lost.

PMID- 25959094
TI  - Mapping intrinsic functional brain changes and repetitive transcranial magnetic
      stimulation neuromodulation in idiopathic restless legs syndrome: a resting-state
      functional magnetic resonance imaging study.
AB  - OBJECTIVE: The objectives of this study were, first, to explore differences in
      brain activity between normal people and idiopathic restless legs syndrome (RLS)
      patients during asymptomatic periods; and, second, to determine whether
      administering repetitive transcranial magnetic stimulation (rTMS) to specific
      cortical regions would reverse any observed differences in brain activity and
      alleviate patient symptoms. METHODS: Fifteen idiopathic RLS patients (nine drug
      naive patients) and 14 gender- and age-matched healthy controls were enrolled.
      Resting-state functional magnetic resonance imaging was used to measure the
      amplitude of low-frequency fluctuations (ALFF) in spontaneous brain activity
      during asymptomatic periods. Seven patients received high-frequency (5 Hz) rTMS
      directed toward the leg area of the primary motor cortex. Scores on the
      International Restless Legs Syndrome Study Group (IRLSSG) Rating Scale and ALFF
      values were measured before and after treatment. RESULTS: Compared with healthy
      controls, RLS patients showed lower ALFF in the sensorimotor and visual
      processing regions, and higher ALFF in the insula, parahippocampal and
      hippocampal gyri, left posterior parietal areas, and brainstem. These results
      were largely conserved when only drug-naive patients were considered. After rTMS
      treatment, ALFF in several sensorimotor and visual regions were significantly
      elevated and IRLSSG Rating Scale scores decreased, indicating improved RLS
      symptoms. CONCLUSIONS: High-frequency rTMS delivered to the leg area of the
      primary motor cortex may raise functional activity in the sensorimotor and
      occipital regions, leading to improve symptoms in RLS patients. These results
      provide novel insight into RLS pathophysiology and suggest a potential mechanism
      for rTMS therapy in idiopathic RLS patients.

PMID- 25959093
TI  - Prospective associations between sedentary time, sleep duration and adiposity in
      adolescents.
AB  - OBJECTIVE: The objective of this study was to investigate whether objectively
      measured sedentary time and sleep duration are associated with changes in
      adiposity from mid- to late adolescence. METHODS: Students (n = 504, 42% boys)
      were recruited from schools in Cambridgeshire, UK. At baseline (mean age 15.0 +/-
      0.3 years), sedentary time was objectively measured by >=3 days of combined heart
      rate and movement sensing. Concurrently, sleep duration was measured by combined
      sensing in conjunction with self-reported bed times. Fat mass index (FMI;
      kg/m(2)) was estimated at baseline and follow-up (17.5 +/- 0.3 years) by
      anthropometry and bioelectrical impedance. FMI change (DeltaFMI) was calculated
      by subtracting the baseline from follow-up values. Linear regression models
      adjusted for basic demographics, moderate-to-vigorous physical activity (MVPA),
      and depressive symptoms were used to investigate associations of sedentary time
      and sleep duration (mutually adjusted for one another) with DeltaFMI. RESULTS:
      FMI increased by 0.5 and 0.6 kg/m(2) in boys and girls, respectively, but there
      was no association between sedentary time and DeltaFMI in either gender (p >=
      0.087), and no association between sleep duration and DeltaFMI in girls (p >=
      0.61). In boys, each additional hour of baseline sleep significantly reduced the
      DeltaFMI by 0.13 kg/m(2) (p = 0.049), but there was little evidence for this
      association after adjusting for MVPA and depressive symptoms (p = 0.15).
      CONCLUSIONS: Sedentary time may not determine changes in adiposity from mid- to
      late adolescence, nor may sleep duration in girls. However, sleep length may be
      inversely associated with adiposity gain in boys, depending on whether the
      relationship is confounded or mediated by MVPA and depression.

PMID- 25959095
TI  - The longitudinal effects of persistent periodic breathing on cerebral oxygenation
      in preterm infants.
AB  - OBJECTIVES: Periodic breathing is common in preterm infants, but is thought to be
      benign. The aim of our study was to assess the incidence and impact of periodic
      breathing on heart rate (HR), oxygen saturation (SpO2), and brain tissue
      oxygenation index (TOI) over the first six months after term-equivalent age.
      STUDY DESIGN: Twenty-four preterm infants (27-36 weeks gestational age) were
      studied with daytime polysomnography in quiet sleep (QS) and active sleep (AS)
      and in both the prone and supine positions at 2-4 weeks, 2-3 months, and 5-6
      months post-term corrected age. HR, SpO2, and TOI (NIRO-200 spectrophotometer)
      were recorded. Periodic breathing episodes were defined as greater than or equal
      to three sequential apneas each lasting >=3 s. RESULTS: A total 164 individual
      episodes of periodic breathing were recorded in 19 infants at 2-4 weeks, 62 in 12
      infants at 2-3 months, and 35 in 10 infants at 5-6 months. There was no effect of
      gestational age on periodic breathing frequency or duration. Falls in HR (-21.9
      +/- 2.7%) and TOI (-13.1 +/- 1.5%) were significantly greater at 2-3 months of
      age compared to 2-4 weeks of age. CONCLUSIONS: The majority of preterm infants
      discharged home without clinical respiratory problems had persistent periodic
      breathing. Although in most infants periodic breathing was not associated with
      significant falls in SpO2 or TOI, several infants had significant desaturations
      and reduced cerebral oxygenation especially during AS. The clinical significance
      of this on neurodevelopmental outcome is unknown and warrants further
      investigations.

PMID- 25959096
TI  - Bucindolol hydrochloride in atrial fibrillation and concomitant heart failure.
AB  - Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and it
      increases the risk of thromboembolic stroke and death. AF is common in patients
      with heart failure and reduced ejection fraction (HFrEF), affecting between 30
      and 40% of patients with HFrEF. AF increases the risk of death and
      hospitalization in patients with HFrEF. Only two antiarrhythmic drugs (amiodarone
      and dofetilide) are guideline-recommended in patients with AF and heart failure
      (HF). Meta-analyses of studies of major trials in HF suggest that patients with
      AF/HFrEF do not benefit from conventional beta-blockers. Bucindolol has shown
      promise in the treatment of patients with AF/HFrEF. We will explore how the
      shared pathophysiology of AF/HF is targeted by the unique pharmacology of
      bucindolol and review the existing data for bucindolol in AF/HF. We will explore
      findings that support a pharmacogenetically modulated effect of bucindolol in
      patients with polymorphisms in beta1-adrenergic receptor and provide an overview
      of ongoing studies. 

PMID- 25959097
TI  - Tail-scope: Using friends to estimate heavy tails of degree distributions in
      large-scale complex networks.
AB  - Many complex networks in natural and social phenomena have often been
      characterized by heavy-tailed degree distributions. However, due to rapidly
      growing size of network data and concerns on privacy issues about using these
      data, it becomes more difficult to analyze complete data sets. Thus, it is
      crucial to devise effective and efficient estimation methods for heavy tails of
      degree distributions in large-scale networks only using local information of a
      small fraction of sampled nodes. Here we propose a tail-scope method based on
      local observational bias of the friendship paradox. We show that the tail-scope
      method outperforms the uniform node sampling for estimating heavy tails of degree
      distributions, while the opposite tendency is observed in the range of small
      degrees. In order to take advantages of both sampling methods, we devise the
      hybrid method that successfully recovers the whole range of degree distributions.
      Our tail-scope method shows how structural heterogeneities of large-scale complex
      networks can be used to effectively reveal the network structure only with
      limited local information. 

PMID- 25959099
TI  - High level of IFN-gamma released from whole blood of human tuberculosis
      infections following stimulation with Rv2073c of Mycobacterium tuberculosis.
AB  - More efficacious and specific biomarkers are urgently needed for better control
      of tuberculosis (TB), the second leading infectious cause of mortality worldwide.
      The region of difference 9 (RD9) presents the genome of the causative pathogen
      Mycobacterium tuberculosis rather than other species of the genus Mycobacterium,
      which might be promising targets for specific diagnosis, vaccine development and
      pathogenesis. In this study, two proteins Rv2073c and Rv2074, encoded by the RD9
      were expressed and purified from Escherichia coli system. Following stimulation
      with both proteins, the levels of IFN-gamma secreted by T cells from a total of
      49 whole blood samples obtained from clinically diagnosed active TB patients,
      patients with latent TB infections (LTBIs), and healthy donors, were compared
      with those of the incubation with recombinant fusion protein of CFP21 and MPT64
      (rCM). Our results demonstrated that only Rv2073c could induce a higher level of
      IFN-gamma in TB infections than healthy controls and there was a positive
      correlation between Rv2073c- and rCM-specific IFN-gamma levels in TB infections
      and healthy donors, respectively. These findings indicate that Rv2073c might be a
      promising antigen for specific diagnostic reagents and vaccine candidates of TB. 

PMID- 25959098
TI  - The transgenic cloned pig population with integrated and controllable GH
      expression that has higher feed efficiency and meat production.
AB  - Sustained expression of the GH gene has been shown to have detrimental effects on
      the health of animals. In the current study, transgenic founder pigs, with
      controllable pig growth hormone (pGH) expression, were cloned via the handmade
      cloning method (HMC), and pGH expression levels were examined at the cellular and
      organismal levels. The serum pGH levels in 3 founder male pigs were found to be
      significantly higher after induction with intramuscular injection of doxycycline
      (DOX) compared to baseline. A daily dose of DOX was administered via feed to
      these animals for a period of 65 to 155 days. The growth rate, feed efficiency
      and pGH serum concentration increased in the DOX-induced transgenic group
      compared with the other groups. 8 numbers of animals were euthanized and the
      dressing percentage, loin muscle and lean meat percentage were significantly
      higher in the DOX-induced F1 transgenic group compared with the other groups. In
      this study a large population of transgenic pigs, with integrated controllable
      expression of a transgene, was obtained. The transgenic pigs were healthy and
      normal in terms of reproductive capability. At the same time, feed efficiency was
      improved, production processes were accelerated and meat yield was increased. 

PMID- 25959100
TI  - Use of radioactive substances in diagnosis and treatment of neuroendocrine
      tumors.
AB  - Radionuclides are needed both for nuclear medicine imaging as well as for peptide
      receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NET). Imaging is
      important in the initial diagnostic work-up and for staging NETs. In therapy
      planning, somatostatin receptor imaging (SRI) is used when treatment is targeted
      at the somatostatin receptors as with the use of somatostatin analogues or PRRT.
      SRI with gamma camera technique using the tracer (111)In-DTPA-octreotide has for
      many years been the backbone of nuclear imaging of NETs. However, increasingly
      PET tracers for SRI are now used. (68)Ga-DOTATATE, (68)Ga-DOTATOC and (68)Ga
      DOTANOC are the three most often used PET tracers. They perform better than SPECT
      tracers and should be preferred. FDG-PET is well suited for visualization of most
      of the somatostatin receptor-negative tumors prognostic in NET patients. Also
      (11)C-5-HTP, (18)F-DOPA and (123)I-MIBG may be used in NET. However, with FDG-PET
      and somatostatin receptor PET at hand we see limited necessity of other tracers.
      PRRT is an important tool in the treatment of advanced NETs causing complete or
      partial response in 20% and minor response or tumor stabilization in 60% with
      response duration of up to 3 years. Grade 3-4 kidney or bone marrow toxicity is
      seen in 1.5% and 9.5%, respectively, but are completely or partly reversible in
      most patients. (177)Lu-DOTATATE seems to have less toxicity than (90)Y-DOTATOC.
      However, until now only retrospective, non-randomized studies have been performed
      and the role of PRRT in treatment of NETs remains to be established. 

PMID- 25959102
TI  - Why is uranyl formohydroxamate red?
AB  - The complexation of UO2(2+) by formohydroxamate (FHA(-)) creates solutions with
      dark red coloration. The inherent redox activity of formohydroxamate leads to the
      possibility that these solutions contain U(V) complexes, which are often red. We
      demonstrate that the reaction of U(VI) with formohydroxamate does not result in
      reduction, but rather in formation of the putative cis-aquo UO2(FHA)2(H2O)2,
      whose polymeric solid-state structure, UO2(FHA)2, contains an unusually bent
      UO2(2+) unit and a highly distorted coordination environment around a U(VI)
      cation in general. The bending of the uranyl cation results from unusually strong
      pi donation from the FHA(-) ligands into the 6d and 5f orbitals of the U(VI)
      cation. The alteration of the bonding in the uranyl unit drastically changes its
      electronic and vibrational features. 

PMID- 25959104
TI  - Do you have a right to decide? Or do we have a right to acquiesce?
AB  - Clinicians make decisions about patient management on a daily basis and are
      required to act in a way that is both legally and ethically correct. To act
      legally requires compliance with a set of rules which reflect the values and
      interests of society. Ethical decisions are based on what we believe as a group
      to be morally right. Morals are, however, unique to the individual. Balancing the
      legal, ethical and moral dimensions of clinical decisions has the potential,
      therefore, to generate conflict for the individual practitioner. In this paper we
      report a case study of a patient with a high cervical spine injury resulting in
      quadriplegia, without prospect of a ventilator independent life. The patient, who
      was assessed as having capacity to make decisions, subsequently elected to have
      treatment withdrawn. In this case, withdrawal of treatment constituted removal of
      mechanical ventilation which ultimately resulted in death. The patient also
      requested for his organs to be donated after he was deceased. This case study, to
      our knowledge, is the first report of donation after cardiac death following a
      high cervical spinal injury in a cognitively intact patient. As such, this case
      study allows us to discuss the moral, ethical and legal implications of donation
      after cardiac death following withdrawal of medical treatment.

PMID- 25959105
TI  - Tumor necrosis factor-alpha expression in patients with obstructive benign
      prostatic hyperplasia is associated with a higher incidence of asymptomatic
      inflammatory prostatitis NIH category IV and prostatic calcification.
AB  - OBJECTIVE: The aim of this study was to investigate the association of the
      expression of tumor necrosis factor-alpha (TNF-alpha) with asymptomatic
      inflammatory prostatitis National Institutes of Health (NIH) category IV and
      prostatic calculi, in patients with obstructive benign prostatic hyperplasia
      (BPH) treated by transurethral electroresection of the prostate (TURP). MATERIALS
      AND METHODS: Ninety-six patients with obstructive BPH and TURP were evaluated in
      a prospective study. Based on a preoperative transrectal ultrasound examination
      of the prostate gland, patients were divided into two groups, one with prostatic
      calculi (n = 31) and one without (n = 65). Prostatitis NIH category IV was
      classified according to Irani's histological grading system (Irani et al. J Urol
      1997;157:1301-3). Associations between the incidence of prostatic calculi,
      histological prostatitis, TNF-alpha expression, prostate-specific antigen, uric
      acid, cholesterol, triglycerides, C-reactive protein, International Prostate
      Symptom Score (IPSS), the International Index for Erectile Function (IIEF-5) and
      the NIH-Chronic Prostatitis Symptom Index Score (NIH-CPSI) were analyzed.
      RESULTS: Prostatitis was confirmed by histological investigation in 71.9% of
      patients: 83.9% of those with prostatic calculi versus 66.1% of those without (p
      < 0.04). TNF-alpha expression was significantly higher in patients with prostatic
      calculi. Association calculations yielded significant values for the severity
      (histological grading) of inflammation (p < 0.029), TNF-alpha expression (p <
      0.007), uric acid (p < 0.005), cholesterol (p < 0.028) and the NIH-CPS subdomain
      of urinary symptoms (p < 0.044) in patients with prostatic calculi. CONCLUSIONS:
      In patients with obstructive BPH, prostatic calculi were found on ultrasound in
      one-third of the cases, and histological NIH category IV prostatitis in two
      thirds of cases. The incidence of both prostatitis NIH category IV and TNF-alpha
      expression was significantly higher in patients with prostatic calculi than in
      those without.

PMID- 25959103
TI  - Fibroblast-specific upregulation of Flightless I impairs wound healing.
AB  - The cytoskeletal protein Flightless (Flii) is a negative regulator of wound
      healing. Upregulation of Flii is associated with impaired migration,
      proliferation and adhesion of both fibroblasts and keratinocytes. Importantly,
      Flii translocates from the cytoplasm to the nucleus in response to wounding in
      fibroblasts but not keratinocytes. This cell-specific nuclear translocation of
      Flii suggests that Flii may directly regulate gene expression in fibroblasts,
      providing one potential mechanism of action for Flii in the wound healing
      response. To determine whether the tissue-specific upregulation of Flii in
      fibroblasts was important for the observed inhibitory effects of Flii on wound
      healing, an inducible fibroblast-specific Flii overexpressing mouse model was
      generated. The inducible ROSA26 system allowed the overexpression of Flii in a
      temporal and tissue-specific manner in response to tamoxifen treatment. Wound
      healing in the inducible mice was impaired, with wounds at day 7 postwounding
      significantly larger than those from non-inducible controls. There was also
      reduced collagen maturation, increased myofibroblast infiltration and elevated
      inflammation. The impaired healing response was similar in magnitude to that
      observed in mice with non-tissue-specific upregulation of Flii suggesting that
      fibroblast-derived Flii may have an important role in the wound healing response.

PMID- 25959101
TI  - Liver transplantation in the Nordic countries - An intention to treat and post
      transplant analysis from The Nordic Liver Transplant Registry 1982-2013.
AB  - AIM AND BACKGROUND: The Nordic Liver Transplant Registry (NLTR) accounts for all
      liver transplants performed in the Nordic countries since the start of the
      transplant program in 1982. Due to short waiting times, donor liver allocation
      has been made without considerations of the model of end-stage liver disease
      (MELD) score. We aimed to summarize key outcome measures and developments for the
      activity up to December 2013. MATERIALS AND METHODS: The registry is integrated
      with the operational waiting-list and liver allocation system of
      Scandiatransplant (www.scandiatransplant.org) and accounted at the end of 2013
      for 6019 patients out of whom 5198 were transplanted. Data for recipient and
      donor characteristics and relevant end-points retransplantation and death are
      manually curated on an annual basis to allow for statistical analysis and the
      annual report. RESULTS: Primary sclerosing cholangitis, acute hepatic failure,
      alcoholic liver disease, primary biliary cirrhosis and hepatocellular carcinoma
      are the five most frequent diagnoses (accounting for 15.3%, 10.8%, 10.6%, 9.3%
      and 9.0% of all transplants, respectively). Median waiting time for non-urgent
      liver transplantation during the last 10-year period was 39 days. Outcome has
      improved over time, and for patients transplanted during 2004-2013, overall one-,
      five- and 10-year survival rates were 91%, 80% and 71%, respectively. In an
      intention-to-treat analysis, corresponding numbers during the same time period
      were 87%, 75% and 66%, respectively. CONCLUSION: The liver transplant program in
      the Nordic countries provides comparable outcomes to programs with a MELD-based
      donor liver allocation system. Unique features comprise the diagnostic spectrum,
      waiting times and the availability of an integrated waiting list and transplant
      registry (NLTR).

PMID- 25959106
TI  - KLIC-score for predicting early failure in prosthetic joint infections treated
      with debridement, implant retention and antibiotics.
AB  - Debridement, irrigation and antibiotic treatment form the current approach in
      early prosthetic joint infection (PJI). Our aim was to design a score to predict
      patients with a higher risk of failure. From 1999 to 2014 early PJIs were
      prospectively collected and retrospectively reviewed. The primary end-point was
      early failure defined as: 1) the need for unscheduled surgery, 2) death-related
      infection within the first 60 days after debridement or 3) the need for
      suppressive antibiotic treatment. A score was built-up according to the logistic
      regression coefficients of variables available before debridement. A total of 222
      patients met the inclusion criteria. The most frequently isolated microorganisms
      were coagulase-negative staphylococci (95 cases, 42.8%) and Staphylococcus aureus
      (81 cases, 36.5%). Treatment of 52 (23.4%) cases failed. Independent predictors
      of failure were: chronic renal failure (OR 5.92, 95% CI 1.47-23.85), liver
      cirrhosis (OR 4.46, 95% CI 1.15-17.24), revision surgery (OR 4.34, 95% CI 1.34
      14.04) or femoral neck fracture (OR 4.39, 95% CI1.16-16.62) compared with primary
      arthroplasty, C reactive protein >11.5 mg/dL (OR 12.308, 95% CI 4.56-33.19),
      cemented prosthesis (OR 8.71, 95% CI 1.95-38.97) and when all intraoperative
      cultures were positive (OR 6.30, 95% CI 1.84-21.53). A score for predicting the
      risk of failure was designed using preoperative factors (KLIC-score: Kidney,
      Liver, Index surgery, Cemented prosthesis and C-reactive protein value) and it
      ranged between 0 and 9.5 points. Patients with scores of <=2, >2-3.5, 4-5, >5-6.5
      and >=7 had failure rates of 4.5%, 19.4%, 55%, 71.4% and 100%, respectively. The
      KLIC-score was highly predictive of early failure after debridement. In the
      future, it would be necessary to validate our score using cohorts from other
      institutions.

PMID- 25959107
TI  - The ability of genetically lean or fat slow-growing chickens to synthesize and
      store lipids is not altered by the dietary energy source.
AB  - The increasing use of unconventional feedstuffs in chicken's diets results in the
      substitution of starch by lipids as the main dietary energy source. To evaluate
      the responses of genetically fat or lean chickens to these diets, males of two
      experimental lines divergently selected for abdominal fat content were fed
      isocaloric, isonitrogenous diets with either high lipid (80 g/kg), high fiber (64
      g/kg) contents (HL), or low lipid (20 g/kg), low fiber (21 g/kg) contents (LL)
      from 22 to 63 days of age. The diet had no effect on growth performance and did
      not affect body composition evaluated at 63 days of age. Glycolytic and oxidative
      energy metabolisms in the liver and glycogen storage in liver and Sartorius
      muscle at 63 days of age were greater in chicken fed LL diet compared with
      chicken fed HL diet. In Pectoralis major (PM) muscle, energy metabolisms and
      glycogen content were not different between diets. There were no dietary
      associated differences in lipid contents of the liver, muscles and abdominal fat.
      However, the percentages of saturated (SFA) and monounsaturated fatty acids
      (MUFA) in tissue lipids were generally higher, whereas percentages of
      polyunsaturated fatty acids (PUFA) were lower for diet LL than for diet HL. The
      fat line had a greater feed intake and average daily gain, but gain to feed ratio
      was lower in that line compared with the lean line. Fat chickens were heavier
      than lean chickens at 63 days of age. Their carcass fatness was higher and their
      muscle yield was lower than those of lean chickens. The oxidative enzyme
      activities in the liver were lower in the fat line than in the lean line, but
      line did not affect energy metabolism in muscles. The hepatic glycogen content
      was not different between lines, whereas glycogen content and glycolytic
      potential were higher in the PM muscle of fat chickens compared with lean
      chickens. Lipid contents in the liver, muscles and abdominal fat did not differ
      between lines, but fat chickens stored less MUFA and more PUFA in abdominal fat
      and muscles than lean chickens. Except for the fatty acid composition of liver
      and abdominal fat, no interaction between line and diet was observed. In
      conclusion, the amount of lipids stored in muscles and fatty tissues by lean or
      fat chickens did not depend on the dietary energy source. 

PMID- 25959108
TI  - Evaluation of accelerated corneal collagen cross-linking for the treatment of
      bullous keratopathy in eight dogs (10 eyes).
AB  - OBJECTIVE: Bullous keratopathy (BK) is a serious corneal condition leading to
      impaired vision and ocular pain, due to chronic corneal edema and recurrent
      superficial ulceration. BK is refractory to conventional therapy. In human
      patients, corneal collagen cross-linking (CXL) has been used for the treatment of
      BK, and CXL treatment was recently described for canine patients. The aim of this
      study was to evaluate the clinical and pachymetric effects of accelerated CXL in
      dogs affected by BK. ANIMAL STUDIED: Eight dogs (10 eyes) with BK underwent
      accelerated CXL. PROCEDURES: CXL treatment comprised 30 min of riboflavin-dextran
      instillation, followed by 3 min of UVA irradiation at 30 mW/cm2. Ocular pain,
      corneal edema, corneal ulceration, and pachymetry were evaluated 7, 14, 30, 90,
      and 180 days after treatment. RESULTS: Corneal ulceration and ocular pain were
      resolved by 1 week after CXL treatment and did not recur during the 6-month
      follow-up period. Corneal edema improved in the first 3 months, but worsened from
      months 3 to 6. Corneal thickness initially decreased, but returned to baseline by
      6 months post-CXL. CONCLUSIONS: CXL is a useful treatment option for BK in dogs,
      despite the short-lasting effects on corneal thickness. Patient comfort improved
      rapidly after a single procedure, although CXL did not achieve resolution of
      corneal edema. Treatment protocols may be refined to produce more durable effects
      on corneal edema.

PMID- 25959109
TI  - Application of electron microscopic analysis and fluorescent in situ
      hybridization technique for the successful diagnosis of extraskeletal Ewing's
      sarcoma.
AB  - The diagnosis of soft tissue tumors is often challenging. Immunohistochemical
      investigation, let alone routine histopathological investigation, may not allow
      definitive diagnosis in some cases. To overcome such difficulties, more advanced
      techniques need to be adopted. Herein, we report an extremely rare 56-year-old
      Japanese female case of extraskeletal Ewing's sarcoma (ES), successfully
      diagnosed by electron microscopy (EM) using formalin-fixed sections and
      fluorescence in situ hybridization (FISH). The patient had a 2-year history of a
      tumor growing on the leg. In routine histopathology, invasive proliferation of
      tumor cells was observed in the dermis. Tumor cells were round and uniform with
      large hyperchromatic nuclei, which were positively stained for CD56, VS38c, Ki
      67, MIC2 and vimentin, but not for pan-keratin AE1 + AE3, cytokeratin 20,
      chromogranin A, synaptophysin and neuron-specific enolase. As these findings were
      not conclusive to make the final diagnosis, EM specimens were prepared from
      formalin-fixed sections and subjected to investigation. Cell surface projections
      and dense core granules were detected, suggestive of either Merkel cell carcinoma
      or extraskeletal ES. Subsequent FISH analysis identified reciprocal translocation
      of the ESWR1 gene, enabling the final diagnosis of extraskeletal ES. This study
      provides useful information enabling the diagnosis of this uncommon soft tissue
      tumor. 

PMID- 25959110
TI  - Differences in patients' perceived helpfulness of depression treatment provided
      by general medical providers and specialty mental health providers.
AB  - OBJECTIVE: This study examined the differences in the level of perceived
      helpfulness of treatments received for a major depressive episode (MDE) from a
      general medical provider only, a specialty mental health provider only or both.
      METHOD: This study examined a sample of 8900 respondents from the 2008-2012
      National Survey on Drug Use and Health aged 18-64 who had past 12-month MDE
      (based on criteria specified in the Diagnostic and Statistical Manual of Mental
      Disorders, Fourth edition) and received treatment for depression. Generalized
      ordered logistic regression analyses were conducted to estimate the association
      between the type of treatment providers and perceived helpfulness of depression
      treatment. RESULTS: Adults who received depression treatment from either
      specialty mental health providers alone or from both specialty mental health
      providers and general medical providers in the past year were more likely to
      report that treatment helped them. The differences persisted after adjusting for
      sociodemographic characteristics, comorbid health conditions, receipt of
      depression medication and severity of depression (adjusted odds ratios across
      level of perceived helpfulness ranged from 1.63 to 3.96). CONCLUSIONS: This
      finding calls for greater attention to factors associated with provider type and
      organizational context that may contribute to differences in perceived
      helpfulness of depression treatment.

PMID- 25959111
TI  - Body issues, sexual satisfaction, and relationship status satisfaction in long
      term childhood cancer survivors and healthy controls.
AB  - OBJECTIVE: Research on body image and sexual satisfaction after adult onset
      cancer has shown significant and lasting impairments regarding survivors'
      sexuality and romantic relationships. However, knowledge about these topics and
      their associations in adult survivors of childhood cancer is largely lacking.
      METHODS: Participants completed web-based questionnaires concerning body image,
      body dissociation, sexual satisfaction, and relationship status satisfaction
      (i.e., satisfaction with either being in a relationship or being single).
      Survivors (n = 87) and controls (n = 87) were matched on age and gender, with a
      mean age of 27 years (range: 20-40). Survivors were most often diagnosed with
      leukemia (46%), at an average of 16 years prior to study participation (range: 6
      33 years). RESULTS: Similar numbers of survivors and controls were single (n =
      24/31), in a committed relationship (n = 33/23), or married (n = 30/33).
      Survivors and controls reported comparable levels of body image, body
      dissociation, sexual experiences, and sexual and status satisfaction (d = 0.15
      0.28). Higher status satisfaction was associated with being in a relationship
      (compared with being single, beta = 0.439), more positive body image (beta =
      0.196), and higher sexual satisfaction (beta = 0.200). CONCLUSIONS: Adult
      survivors of childhood cancer were comparable to healthy peers regarding views of
      their bodies and psychosexual development, which was unexpected. Independent of
      whether people experienced cancer or not, their status satisfaction was
      associated with their relationship status, body image, and sexual satisfaction.
      Future research should explore why sexual and body problems are identified after
      adult onset cancer, whereas this seems to be less of a problem in childhood
      cancer survivors.

PMID- 25959112
TI  - In response to "In utero exposure to methotrexate and risk of congenital
      malformations".

PMID- 25959113
TI  - The correlation between metabolic and individual leg mechanical power during
      walking at different slopes and velocities.
AB  - During level-ground walking, mechanical work from each leg is required to
      redirect and accelerate the center of mass. Previous studies show a linear
      correlation between net metabolic power and the rate of step-to-step transition
      work during level-ground walking with changing step lengths. However,
      correlations between metabolic power and individual leg power during step-to-step
      transitions while walking on uphill/downhill slopes and at different velocities
      are not known. This basic understanding of these relationships between metabolic
      demands and biomechanical tasks can provide important information for design and
      control of biomimetic assistive devices such as leg prostheses and orthoses.
      Thus, we compared changes in metabolic power and mechanical power during step-to
      step transitions while 19 subjects walked at seven slopes (0 degrees , +/-3
      degrees , +/-6 degrees , and +/-9 degrees ) and three velocities (1.00, 1.25, and
      1.50m/s). A quadratic model explained more of the variance (R(2)=0.58-0.61) than
      a linear model (R(2)=0.37-0.52) between metabolic power and individual leg
      mechanical power during step-to-step transitions across all velocities. A
      quadratic model explained more of the variance (R(2)=0.57-0.76) than a linear
      model (R(2)=0.52-0.59) between metabolic power and individual leg mechanical
      power during step-to-step transitions at each velocity for all slopes, and
      explained more of the variance (R(2)=0.12-0.54) than a linear model (R(2)=0.07
      0.49) at each slope for all velocities. Our results suggest that it is important
      to consider the mechanical function of each leg in the design of biomimetic
      assistive devices aimed at reducing metabolic costs when walking at different
      slopes and velocities. 

PMID- 25959114
TI  - Quality considerations of paediatric investigation plans for monoclonal
      antibodies: A regulatory perspective from the MHRA.
AB  - Since the advent of the EU Paediatric Regulation in 2007, 78 of the 1688
      Paediatric Investigation Plans (PIPs) have been for monoclonal antibodies (Mabs).
      Of these, 22 have been assessed by the MHRA. The purpose of this mini-review is
      to aid those researching and developing this class of drugs to better understand
      regulatory concerns leading to improved medicinal products for children. Three
      principal quality issues were identified for PIPs under Article 7 and 8: i) the
      level of anti-aggregation stabilisers, ii) acceptability and tolerability of
      administration (i.e. multiple injections, infusion time and volume), and iii) the
      need to develop new presentational forms (e.g. pre-filled syringe). Overall, two
      types of concerns were ascertained - those which are potentially avoidable (e.g.
      through development of new presentational forms) and others which require the
      evolution of new technologies in the sector (e.g. production of concentrated,
      stabilised preparations). 

PMID- 25959115
TI  - Formulation factors affecting acceptability of oral medicines in children.
AB  - Acceptability of medicines in children and caregivers affects safety and
      effectiveness of medicinal treatments. The pharmaceutical industry is required to
      demonstrate acceptability of new paediatric formulations in target age groups as
      an integrated part of the development of these products (Kozarewicz, 2014). Two
      questions arise when trying to tackle this task: "which dosage form to choose for
      each target age group?" and "how to formulate it once the dosage form is
      decided?". Inevitably, both the regulator and the developer turn to scientific
      evidence for answers. Research has emerged in recent years to demonstrate age
      appropriateness and patient acceptability of different dosage forms; however,
      such information is still fragmented and far from satisfactory to define
      efficient formulation development strategies for a diverse patient subset (Ranmal
      and Tuleu, 2013). This paper highlights how formulation factors affect the
      acceptability of different oral medicines in children (Table 1), and it is based
      on a more extensive review article by Liu et al. (Liu et al., 2014). Gaps in
      knowledge are highlighted in order to stimulate further research. In some areas,
      findings from studies conducted in adult populations may provide useful guidance
      for paediatric development and this is also discussed. 

PMID- 25959116
TI  - Milk as a medium for pediatric formulations: Experimental findings and regulatory
      aspects.
AB  - In the case of pediatric medicinal products the selection of an appropriate and
      palatable liquid dosage form can make the difference between treatment success
      and failure. Since the recent adoption of Pediatric Regulations in the U.S. and
      E.U., there is a greater demand for age-appropriate medicines for children.
      Extended research on the use of milk on drug administration in pediatric
      population has shown the multiple benefits of its use. Milk exhibits great
      solubilizing, gastroprotective and taste masking properties, which are very
      important characteristics in the case of insoluble, irritating and bitter-tasting
      active compounds. Milk-based formulations rely on a novel, simple and user
      friendly approach for the delivery of ionized and unionized lipophilic drugs. In
      parallel they can provide critical nutritive elements and a wide range of
      biologically active peptides, very important elements especially for pediatric
      patients. 

PMID- 25959117
TI  - Determination of drug lipophilicity by phosphatidylcholine-modified microemulsion
      high-performance liquid chromatography.
AB  - A new biomembrane-mimetic liquid chromatographic method using a C8 stationary
      phase and phosphatidylcholine-modified (PC-modified) microemulsion mobile phase
      was used to estimate unionized and ionized drugs lipophilicity expressed as an n
      octanol/water partition coefficient (logP and logD). The introduction of PC into
      sodium dodecyl sulfate (SDS) microemulsion yielded a good correlation between
      logk and logD (R(2)=0.8). The optimal composition of the PC-modified
      microemulsion liquid chromatography (PC-modified MELC) mobile phase was 0.2% PC
      3.0% SDS-6.0% n-butanol-0.8% ethyl acetate-90.0% water (pH 7.0) for neutral and
      ionized molecules. The interactions between the analytes and system described by
      this chromatographic method is more similar to biological membrane than the n
      octanol/water partition system. The result in this paper suggests that PC
      modified MELC can serve as a possible alternative to the shake-flask method for
      high-throughput unionized and ionized drugs lipophilicity determination and
      simulation of biological processes. 

PMID- 25959119
TI  - Formulations in paediatric investigation plans (PIPs): Introduction to PIP
      quality section and regulatory framework.

PMID- 25959118
TI  - Developmental pharmacology: A moving target.
AB  - The main characteristic of pediatric and neonatal pharmacotherapy still is the
      insufficient availability of drugs with confirmed efficacy and safety data in
      children. Children differ from adults in the physiological, psychological and
      developmental terms and this subsequently results in differences in anticipated
      drug potency, efficacy and toxicity. This paper is focused on the most prominent
      issues of the contemporary developmental pharmacology. Child's age and
      development can significantly affect drug pharmacokinetics (PK) processes. The
      dosage of drugs for children must be based on the physiological characteristics,
      as well as PK parameters of the drug obtained from the clinical trials with
      children. While knowledge about the impact of developmental changes on drug PK is
      increasing, information regarding pharmacodynamics (PD) is still more limited.
      The examples from clinical and animal data on ontogeny of receptors resulted in
      strong evidence for changes in drug response during development, in addition to
      but independent from PK alterations. In order to improve the use of medicines in
      children, it is essentially to know the complex processes of growth and
      development into the pediatric drug development programs. This is because absence
      of PK/PD data leads to increased risk of over- or under-dosing, adverse reactions
      or inefficiency. 

PMID- 25959120
TI  - Formulating better medicines for children-reflections.

PMID- 25959121
TI  - Improvement of pulmonary absorption of poorly absorbable macromolecules by
      hydroxypropyl-beta-cyclodextrin grafted polyethylenimine (HP-beta-CD-PEI) in
      rats.
AB  - Effects of hydroxypropyl-beta-cyclodextrin grafted polyethylenimine (HP-beta-CD
      PEI) including HP-beta-CD-PEI600, HP-beta-CD-PEI1800, HP-beta-CD-PEI10000 on the
      pulmonary absorption of insulin, calcitonin, 5(6)-carboxyfluorescein (CF) and
      fluorescein isothiocyanate dextrans (FDs) with various molecular weights (FD4,
      FD10 and FD70) were examined by an pulmonary absorption study in rats. Pulmonary
      absorptions of these poorly absorbable drugs were significantly enhanced by HP
      beta-CD-PEI1800 and HP-beta-CD-PEI10000, and HP-beta-CD-PEI1800 with the
      concentration of 5% (w/v) provided maximal absorption enhancing effect on
      pulmonary absorption of these model drugs. The toxicity study demonstrated that
      HP-beta-CD-PEI did not induce any toxic action to rat pulmonary membranes. In
      addition, zeta potential of insulin solution changed to positive by addition of
      various HP-beta-CD-PEI, meanwhile, the degree of positive charge was linearly
      correlated with absorption enhancing effect of HP-beta-CD-PEI, suggesting that
      positive charge of HP-beta-CD-PEI might be related to their absorption enhancing
      mechanisms for enhancing pulmonary absorption of insulin in rats. In conclusion,
      HP-beta-CD-PEI is a potential and safe absorption enhancer for improving
      absorption of hydrophilic macromolecules especially peptide and protein drugs by
      pulmonary delivery. 

PMID- 25959122
TI  - In vitro toxicity of infusion sets depends on their composition, storage time and
      storage conditions.
AB  - Disposable medical devices release toxic leachables during their clinical use.
      Specifically, the individual parts of the infusion sets (the drip chamber, tube,
      flashball and injection site) are composed of numerous chemical compounds that
      can reach the patients' systemic circulation and induce local and systemic toxic
      effects. We aimed to reveal the relative in vitro toxicity of infusion sets from
      the leading vendors that are used in Israel, and to determine its dependence on
      their design and storage time/conditions. We found that leachates of the rubber
      parts were more toxic than those of the other parts of the infusion sets. The
      measured toxicity was affected by the experimental settings: the cells, medium
      composition, exposure duration, and the type of assay applied for toxicity
      assessment. We recommend to use the capillary endothelium cells for in vitro
      toxicity testing of the infusion sets, and refrain from the use of the MTT test
      which is insufficiently reliable, and can lead to artefacts and incorrect
      conclusions. Further investigation is needed to identify the toxic leachables
      from the individual parts of the infusion sets, and to reveal the risk of their
      toxicity during the clinical use of the infusion sets. 

PMID- 25959123
TI  - Factors associated with cognitive impairment in patients with newly diagnosed
      type 2 diabetes: a cross-sectional study.
AB  - OBJECTIVES: Type 2 diabetes (T2DM) is strongly associated with cognitive
      impairment but the factors within T2DM that predispose to cognitive impairment
      are less well understood, while previous studies have investigated samples with
      T2DM of widely varying duration. We aimed to investigate the factors associated
      with cognitive impairment in patients with newly diagnosed T2DM. METHOD: In a
      multi-ethnic sample with T2DM diagnosed in the last 6 months, we assessed
      cognitive function using the 13-item modified telephone interview for cognitive
      status (TICS-M). Cognitive function was assessed both categorically (impairment
      defined as lowest 10% of scores with the remainder as controls) and as continuous
      TICS-M score. Its associations were tested in univariate and multivariate
      analyses with a range of biological, psychological and sociodemographic factors.
      RESULTS: Of 1790 participants, 1680 had a complete TICS-M assessment at baseline.
      After controlling for covariates, older age (p < 0.001) and lower verbal
      intelligence (p < 0.001) were associated with both cognitive impairment and lower
      TICS-M scores, while non-white ethnicity (p < 0.001), female gender (p = 0.02)
      and higher HbA1c (p = 0.002) were associated with lower TICS-M scores. Depression
      (defined as Patient Health Questionnaire-9 score >=10), elevated inflammatory
      markers and body mass index were not associated with cognitive function after
      controlling for covariates. CONCLUSION: Age, verbal intelligence, female gender
      and HbA1c are associated with cognitive performance in T2DM soon after diagnosis.
      Previously reported associations with depression and inflammatory markers may
      occur later as causes or consequences of T2DM. Longitudinal analyses are needed
      to assess potentially modifiable factors predicting cognitive decline in early
      T2DM.

PMID- 25959124
TI  - Resveratrol attenuates microvascular inflammation in sepsis via SIRT-1-Induced
      modulation of adhesion molecules in ob/ob mice.
AB  - OBJECTIVE: Obesity, a sirtuin-1 (SIRT-1) -deficient state, increases morbidity
      and resource utilization in critically ill patients. SIRT-1 deficiency increases
      microvascular inflammation and mortality in early sepsis. The objective of the
      study was to study the effect of resveratrol (RSV), a SIRT-1 activator, on
      microvascular inflammation in obese septic mice. METHODS: ob/ob and C57Bl/6 (WT)
      mice were pretreated with RSV versus dimethyl sulfoxide (DMSO) (vehicle) prior to
      cecal ligation and puncture (sepsis). We studied (1) leukocyte/platelet adhesion,
      (2) E-selectin, ICAM-1, and SIRT-1 expression in small intestine, and (3) 7-day
      survival. A group of RSV-treated mice received SIRT-1 inhibitor (EX-527) with
      sepsis induction, and leukocyte/platelet adhesion and E-selectin/ICAM-1
      expression were studied. We treated endothelial (HUVEC) cells with RSV to study E
      selectin/ICAM-1 and p65-acetylation (AC-p65) in response to lipopolysaccharide
      (LPS). RESULTS: RSV treatment decreased leukocyte/platelet adhesion and E
      selectin/ICAM-1 expression with increased SIRT-1 expression in septic ob/ob and
      WT mice, decreased E-selectin/ICAM-1 expression via increased SIRT-1 expression,
      and decreased AC-p65 expression in HUVEC. EX-527 abolished RSV-induced
      attenuation of microvascular inflammation in ob/ob septic mice. Finally, ob/ob
      mice in the sepsis+RSV group had significantly increased 7-day survival versus
      the sepsis+vehicle group. CONCLUSIONS: RSV increases SIRT-1 expression in ob/ob
      septic mice to reduce microvascular inflammation and improves survival.

PMID- 25959125
TI  - Immunochromatographic test of pneumococcal antigen performed on cerebrospinal
      fluid for pneumococcal pneumoniae.

PMID- 25959126
TI  - C/EBPbeta Mediates TNF-alpha-Induced Cancer Cell Migration by Inducing MMP
      Expression Dependent on p38 MAPK.
AB  - Tumor necrosis factor (TNF)-alpha is a pleiotropic cytokine that triggers cell
      proliferation, cell death, or inflammation. Besides its cytotoxic effect on
      cancer cells, TNF-alpha exerts tumor promoting activity. Aberrant TNF-alpha
      signaling promotes cancer cell motility, invasiveness, and enhances cancer
      metastasis. Exaggerated tumor cell migration, invasion, and metastasis by TNF
      alpha has been attributed to the activation of NF-kappaB signaling. It is yet to
      be elucidated if other signaling pathways and effector molecules are involved in
      TNF-alpha-induced cancer cell migration and metastasis. Expression of C/EBPbeta,
      a transcription factor involved in metabolism, inflammation, and cancer, is
      increased upon TNF-alpha treatment. TNF-alpha induces C/EBPbeta expression by
      enhancing its transcription and protein stability. Activation of p38 MAPK, but
      not NF-kappaB or JNK, is responsible for TNF-alpha-induced stabilization of
      C/EBPbeta protein. C/EBPbeta is involved in TNF-alpha-induced cancer cell
      migration. Knockdown of C/EBPbeta inhibits TNF-alpha-induced cell migration,
      while overexpression of C/EBPbeta increases migration of cancer cells. C/EBPbeta
      is translated into transcriptional activator LAP1 and LAP2 and transcriptional
      repressor LIP utilizing alternative in-frame translation start sites. Despite TNF
      alpha induces expression of all three isoforms, LAP1/2, but not LIP, promote
      cancer cell migration. TNF-alpha induced MMP1/3 expression, which was abrogated
      by C/EBPbeta knockdown or p38 MAPK inhibition. MMP inhibitor or knockdown of
      MMP1/3 diminished TNF-alpha- and C/EBPbeta-induced cell migration. Thus,
      C/EBPbeta mediates TNF-alpha-induced cancer cell migration by inducing MMP1/3
      expression, and may participate in the regulation of inflammation-associated
      cancer metastasis.

PMID- 25959127
TI  - Ordering of PCDTBT revealed by time-resolved electron paramagnetic resonance
      spectroscopy of its triplet excitons.
AB  - Time-resolved electron paramagnetic resonance (TREPR) spectroscopy is shown to be
      a powerful tool to characterize triplet excitons of conjugated polymers. The
      resulting spectra are highly sensitive to the orientation of the molecule. In
      thin films cast on PET film, the molecules' orientation with respect to the
      surface plane can be determined, providing access to sample morphology on a
      microscopic scale. Surprisingly, the conjugated polymer investigated here, a
      promising material for organic photovoltaics, exhibits ordering even in bulk
      samples. Orientation effects may significantly influence the efficiency of solar
      cells, thus rendering proper control of sample morphology highly important. 

PMID- 25959128
TI  - Diagnostic value of the rectal ammonia tolerance test, fasting plasma ammonia and
      fasting plasma bile acids for canine portosystemic shunting.
AB  - Portosystemic shunting (PSS) often results in hyperammonaemia and, consequently,
      hepatic encephalopathy. This retrospective study evaluated the sensitivity,
      specificity, positive and negative predictive values (PPV and NPV, respectively)
      and other test performance metrics for the ammonia tolerance test (ATT), serum
      fasting bile acids (FBA), serum fasting ammonia concentration (FA), and
      combinations of these tests for their association with PSS in dogs. Medical
      records of 271 dogs suspect for PSS (symptomatic group) and 53 dogs returning for
      evaluation after surgical closure of a congenital PSS (CPSS post-surgical control
      group) were analysed. In the symptomatic group, ATT at 40 min (T40), and the FBA
      had the highest sensitivity (100% and 98%, respectively) and NPV (100% and 96%,
      respectively) for PSS. The combination of increased FBA and FA had the highest
      specificity (97%), with a PPV of 97%, and a positive likelihood ratio of 29. In
      the CPSS post-surgical control group, the specificity and PPV of FA and the
      combination of increased FBA/FA were both 100%. In purebred populations, the NPV
      of all tests was 100%. Consequently, PSS would be ruled out in a symptomatic dog
      with normal FBA or ATT (T40) and would be highly probable when both FBA and FA
      are increased. Increased FA was conclusive for PSS in dogs evaluated for post
      surgical closure of a CPSS. FBA was the most suitable test for screening
      purposes. 

PMID- 25959129
TI  - Evidence of horsemanship and dogmanship and their application in veterinary
      contexts.
AB  - This review collates peer-reviewed evidence for desirable attributes for those
      who work with dogs and horses. It is written with a particular focus on the
      veterinary profession. Although veterinarians and veterinary nurses (VNs) occupy
      variable roles when interacting with their patients, several behavioural
      attributes emerge as helpful across the range of such roles. In light of recent
      research on the value of considering animals' arousal and affective state as
      predictors of behaviour and welfare, best practice in human-horse and human-dog
      interactions is outlined. The attributes of affiliation, safety and positive
      reinforcement seem to contribute greatly to the development and maintenance of
      moderate arousal and positive affect in animals. The information in this review
      article is offered in an attempt to show why veterinary professionals with good
      horsemanship are likely to remain safe, and to introduce the concept of
      dogmanship. In the light of the peer-reviewed evidence assembled here, it is
      arguable that veterinary teams, comprising both veterinarians and VNs, can become
      scholars in these areas. The benefits of this approach for practitioner safety,
      animal welfare and client satisfaction are likely to be significant. 

PMID- 25959130
TI  - How well do vaccines against Bordetella bronchiseptica work in dogs?

PMID- 25959131
TI  - Closed-loop ARS mode for scanning ion conductance microscopy with improved speed
      and stability for live cell imaging applications.
AB  - Scanning ion conductance microscopy (SICM) is an increasingly useful
      nanotechnology tool for non-contact, high resolution imaging of live biological
      specimens such as cellular membranes. In particular, approach-retract-scanning
      (ARS) mode enables fast probing of delicate biological structures by rapid and
      repeated approach/retraction of a nano-pipette tip. For optimal performance,
      accurate control of the tip position is a critical issue. Herein, we present a
      novel closed-loop control strategy for the ARS mode that achieves higher
      operating speeds with increased stability. The algorithm differs from that of
      most conventional (i.e., constant velocity) approach schemes as it includes a
      deceleration phase near the sample surface, which is intended to minimize the
      possibility of contact with the surface. Analysis of the ion current and tip
      position demonstrates that the new mode is able to operate at approach speeds of
      up to 250 MUm s(-1). As a result of the improved stability, SICM imaging with the
      new approach scheme enables significantly improved, high resolution imaging of
      subtle features of fixed and live cells (e.g., filamentous structures & membrane
      edges). Taken together, the results suggest that optimization of the tip approach
      speed can substantially improve SICM imaging performance, further enabling SICM
      to become widely adopted as a general and versatile research tool for biological
      studies at the nanoscale level. 

PMID- 25959132
TI  - A microfabricated magnetic actuation device for mechanical conditioning of arrays
      of 3D microtissues.
AB  - This paper describes an approach to actuate magnetically arrays of microtissue
      constructs for long-term mechanical conditioning and subsequent biomechanical
      measurements. Each construct consists of cell/matrix material self-assembled
      around a pair of flexible poly(dimethylsiloxane) (PDMS) pillars. The deflection
      of the pillars reports the tissues' contractility. Magnetic stretching of
      individual microtissues via magnetic microspheres mounted on the cantilevers has
      been used to elucidate the tissues' elastic modulus and response to varying
      mechanical boundary conditions. This paper describes the fabrication of arrays of
      micromagnetic structures that can transduce an externally applied uniform
      magnetic field to actuate simultaneously multiple microtissues. These structures
      are fabricated on silicon-nitride coated Si wafers and contain electrodeposited
      Ni bars. Through-etched holes provide optical and culture media access when the
      devices are mounted on the PDMS microtissue scaffold devices. Both static and AC
      forces (up to 20 MUN on each microtissue) at physiological frequencies are
      readily generated in external fields of 40 mT. Operation of the magnetic arrays
      was demonstrated via measurements of elastic modulus and dynamic stiffening in
      response to AC actuation of fibroblast populated collagen microtissues. 

PMID- 25959133
TI  - A Diagonal-Steering-Based Binaural Beamforming Algorithm Incorporating a Diagonal
      Speech Localizer for Persons With Bilateral Hearing Impairment.
AB  - Previously suggested diagonal-steering algorithms for binaural hearing support
      devices have commonly assumed that the direction of the speech signal is known in
      advance, which is not always the case in many real circumstances. In this study,
      a new diagonal-steering-based binaural speech localization (BSL) algorithm is
      proposed, and the performances of the BSL algorithm and the binaural beamforming
      algorithm, which integrates the BSL and diagonal-steering algorithms, were
      evaluated using actual speech-in-noise signals in several simulated listening
      scenarios. Testing sounds were recorded in a KEMAR mannequin setup and two
      objective indices, improvements in signal-to-noise ratio (SNRi ) and segmental
      SNR (segSNRi ), were utilized for performance evaluation. Experimental results
      demonstrated that the accuracy of the BSL was in the 90-100% range when input SNR
      was -10 to +5 dB range. The average differences between the gamma-adjusted and
      gamma-fixed diagonal-steering algorithms (for -15 to +5 dB input SNR) in the
      talking in the restaurant scenario were 0.203-0.937 dB for SNRi and 0.052-0.437
      dB for segSNRi , and in the listening while car driving scenario, the differences
      were 0.387-0.835 dB for SNRi and 0.259-1.175 dB for segSNRi . In addition, the
      average difference between the BSL-turned-on and the BSL-turned-off cases for the
      binaural beamforming algorithm in the listening while car driving scenario was
      1.631-4.246 dB for SNRi and 0.574-2.784 dB for segSNRi . In all testing
      conditions, the gamma-adjusted diagonal-steering and BSL algorithm improved the
      values of the indices more than the conventional algorithms. The binaural
      beamforming algorithm, which integrates the proposed BSL and diagonal-steering
      algorithm, is expected to improve the performance of the binaural hearing support
      devices in noisy situations. 

PMID- 25959134
TI  - [Key messages for the initial management of the elderly patient with acute heart
      failure].
AB  - Acute heart failure is a high prevalence geriatric syndrome that has become one
      of the most frequent causes of visits to emergency departments, as well as
      hospital admission, and is associated with high morbidity, mortality and
      functional impairment. There has been an increasing amount of information
      published in recent years on the initial management of acute heart failure and
      the results of the short-term outcomes, as well as the natural history of the
      disease. The objective of this study is to provide several recommendations that
      should be taken into account in the initial management of the elderly patient
      with acute heart failure in the emergency departments, and to review the most
      interesting currently on-going clinical trials. 

PMID- 25959135
TI  - Gastroprotective properties of cashew gum, a complex heteropolysaccharide of
      Anacardium occidentale, in naproxen-induced gastrointestinal damage in rats.
AB  - Long-term use nonsteroidal anti-inflammatory drug is associated with
      gastrointestinal (GI) lesion formation. The aim of this study was to investigate
      the protective activity of cashew gum (CG), a complex heteropolysaccharide
      extracted from Anacardium occidentale on naproxen (NAP)-induced GI damage. Male
      Wistar rats were pretreated with vehicle or CG (1, 3, 10, and 30 mg/kg, p.o.)
      twice daily for 2 days; after 1 h, NAP (80 mg/kg, p.o.) was administered. The
      rats were euthanized on the 2nd day of treatment, 4 h after NAP administration.
      Stomach lesions were measured using digital calipers. The medial small intestine
      was used for the evaluation of macroscopic lesion scores. Samples of the stomach
      and the intestine were used for histological evaluation, and assays for
      glutathione (GSH), malonyldialdehyde (MDA), and myeloperoxidase (MPO). Additional
      rats were used to measure gastric mucus and secretion. Pretreatment with CG
      reduced the macroscopic and microscopic damage induced by NAP. CG significantly
      attenuated NAP-induced alterations in MPO, GSH, and MDA levels. Furthermore, CG
      returned adherent mucus levels to normal values. These results suggest that CG
      has a protective effect against GI damage via mechanisms that involve the
      inhibition of inflammation and increasing the amount of adherent mucus in mucosa.

PMID- 25959138
TI  - Complete mitochondrial genome of the Critically Endangered Smalltooth Sawfish
      Pristis pectinata (Rajiformes: Pristidae).
AB  - In this study we describe the first complete mitochondrial sequence of the
      Critically Endangered Smalltooth Sawfish Pristis pectinata. It is 16,802 bp in
      length and contains all 37 genes found in typical vertebrate mitogenomes. The
      nucleotide composition of the coding strand is 31.1% A, 26.0% C, 13.1% G and
      28.9% T. There are 29 bp overlaps and 38 short intergenic spaces dispersed in the
      mitogenome. Two start codons (ATG and GTG) and two stop codons (TAG and TAA/T)
      were found in the protein-coding genes. The length of the 22 tRNA genes range
      from 67 bp (tRNA(Ser2)) to 75 bp (tRNA(Leu1)). The control region is 1102 bp in
      length with high A + T (62.0%) and poor G (13.5%) content.

PMID- 25959139
TI  - Problems in comparisons of data for the prevalence of myopia and the frequency
      distribution of ametropia.
AB  - PURPOSE: There is currently great interest in comparing data for the prevalence
      of myopia in different parts of the world, particularly in view of the suggestion
      that, in recent decades, marked increases have occurred in prevalence among
      children and young adults in some areas. This work investigates the factors that
      affect the comparison and interpretation of sets of myopia prevalence data for
      different age groups, locations and dates. RECENT FINDINGS: Using data from the
      literature, the problems caused by the effect of the reliability and validity of
      the method used to measure refraction, the threshold chosen to define an eye as
      myopic are discussed. The influence of slow drifts in refraction with age is
      considered and it is recommended that if mean refractions at different ages are
      to be compared, the interpretation of the results should take account of the
      normal age-dependent trends in refraction. The value of specifying the
      distribution of refractive errors, rather than simply their mean and standard
      deviation, is emphasised and possible parametric fits to describe these
      distributions are reviewed. SUMMARY: There remains a need for greater
      standardisation in sampling strategies, refractive measurement procedures and
      definition of myopia in prevalence studies. The use of an ex-Gaussian or other
      approximations to describe the refractive error distribution appears to give
      useful insights into the nature of the changes that may occur with age and other
      factors.

PMID- 25959136
TI  - Comparative sensitivity of commercial tests for hepatitis E genotype 3 virus
      antibody detection.
AB  - Hepatitis E virus (HEV) acute infection is often diagnosed only by anti-HEV IgM
      ELISA methods, whose sensitivity varies, according to different reports. Reports
      assessing the specificity of commercial assays for anti-HEV IgG testing are
      scarce, and estimates of sensitivity and specificity are both controversial. The
      aim of this work is to assess the sensitivity of different commercial techniques
      for HEV genotype 3 antibody (anti-HEV) IgM and IgG detection in entirely specific
      sample panels including both high and low antibody concentrations. The anti-HEV
      IgM and IgG ELISA methods compared were: DSI, Mikrogen, Wantai, Euroimmun, MP,
      and Dia.pro. The rapid test All Diag was also included in the anti-HEV IgM
      comparison. Our results show that low anti-HEV IgM concentrations were better
      detected by DSI, Mikrogen, and All Diag, these tests being the most sensitive in
      our study. Euroimmun, MP and Dia.pro gave concordant results, showing lower
      sensitivity than the others. Regarding anti-HEV IgG our results revealed similar
      anti-HEV IgG sensitivity. Furthermore, there was a striking overall lack of
      concordance among the results. We present a thorough review of previous
      comparative reports, with particular reference to the anti-HEV IgG comparison,
      since published results differ from ours. This discrepancy may be related to the
      improved versions of the tests for MP and Dia.pro that we employed.

PMID- 25959140
TI  - Proteomic characterization of the qualitative and quantitative differences in
      cervical mucus composition during the menstrual cycle.
AB  - The chemical composition of the cervical mucus (CM), its physical characteristics
      and the volume of secretion change cyclically throughout the menstrual cycle. The
      aim of this study was to identify the constitutive protein composition of CM of
      fertile women and the changes in the CM proteome throughout the menstrual cycle.
      Five fertile women who had a term delivery within 1 year before the study were
      enrolled. Proteomic analysis was performed using an Ultimate 3000 Nano/Micro-HPLC
      apparatus equipped with an FLM-3000-Flow manager module and coupled with an LTQ
      Orbitrap XL hybrid mass spectrometer; bioinformatic software was used for
      functional and quantitative analysis. 59, 81 and 43 proteins (mean) were
      respectively identified in the pre-ovulatory, ovulatory and post-ovulatory
      samples. 38 common proteins were identified. 42, 38 and 17 exclusive proteins
      were respectively identified in pre-ovulatory, ovulatory and post-ovulatory CM.
      The main part of CM constituents has a catalytic activity, which is mainly
      related to hydrolase activity. The label-free quantitative analysis of the common
      proteins revealed a significant reduction in the protein abundance index for
      antileukoproteinase, after the ovulation, and a peak of haptoglobin at ovulation.
      This is the first application of high-resolution MS-based proteomics for the
      identification of protein constituents of CM. This approach may contribute to the
      identification of putative biomarkers of the female reproductive tract. 

PMID- 25959137
TI  - The complete mitochondrial genome of Kaloula rugifera (Amphibia, Anura,
      Microhylidae).
AB  - We determined the complete mitochondrial genome of Kaloula rugifera in this work.
      The mitogenome was 17,073 bp in length, containing 13 protein-coding genes, 2
      rRNA genes, 22 tRNA genes and a control region (D-loop). The base composition of
      the light strand was 29.7% A, 30.4% T, 25.7% C and 14.2% G. The gene order and
      contents of it is identical to most amphibian mitogenome. All protein-coding
      genes began with ATG as start codon except ND1 gene beginning with GTG and COI
      gene beginning with ATA. Five protein-coding genes (COII, ATP 6, COIII, ND3 and
      ND4) ended with incomplete stop codon T. The 22 tRNA genes with the size ranging
      from 65 bp to 73 bp were interspersed along the whole genome. The D-loop region
      containing tandem repetition was 1675 bp in length and heavily biased to A + T
      nucleotides.

PMID- 25959141
TI  - Pigment cell movement is not required for generation of Turing patterns in
      zebrafish skin.
AB  - The zebrafish is a model organism for pattern formation in vertebrates.
      Understanding what drives the formation of its coloured skin motifs could reveal
      pivotal to comprehend the mechanisms behind morphogenesis. The motifs look and
      behave like reaction-diffusion Turing patterns, but the nature of the underlying
      physico-chemical processes is very different, and the origin of the patterns is
      still unclear. Here we propose a minimal model for such pattern formation based
      on a regulatory mechanism deduced from experimental observations. This model is
      able to produce patterns with intrinsic wavelength, closely resembling the
      experimental ones. We mathematically prove that their origin is a Turing
      bifurcation occurring despite the absence of cell motion, through an effect that
      we call differential growth. This mechanism is qualitatively different from the
      reaction-diffusion originally proposed by Turing, although they both generate the
      short-range activation and the long-range inhibition required to form Turing
      patterns. 

PMID- 25959142
TI  - Transition probabilities for four states of alcohol use in adolescence and young
      adulthood: what factors matter when?
AB  - BACKGROUND AND AIMS: Risky single-occasion drinking (RSOD) is a health threat,
      particularly at younger ages. The study aimed to quantify transition
      probabilities (TPs) between abstinence, use of alcohol, RSOD and frequent RSOD,
      and to understand how TPs are associated with key demographic factors. DESIGN:
      Cohort study (baseline, two follow-ups). A Markov model was fitted to estimate
      annual TPs and hazard ratios (HRs) for age, sex and socio-economic status (SES).
      SETTING: Adolescent and young adult general population of Munich (Germany) and
      surrounding areas. PARTICIPANTS: A total of 3021 people aged 14-25 years at
      baseline in 1995 followed-up in 1998/1999 (n = 2548) and 2003-2005 (n = 2210).
      MEASUREMENTS: Alcohol use, RSOD status, age, sex and SES (subjective financial
      situation) were assessed in a standardized interview. FINDINGS: The highest TPs
      (> 65%) were found for staying in the same drinking state. Higher age [hazard
      ratio (HR) for 1-year increase = 0.87, 95% confidence interval (CI) = 0.84-0.91],
      being female (HR = 0.30, 95% CI = 0.21-0.42), and a high SES (HR = 0.64, 95% CI =
      0.43-0.97) were associated with a lower hazard to progress from use to RSOD.
      While age was associated predominantly with transitions between abstinence and
      alcohol use, sex was more relevant for transitions associated with RSOD and
      frequent RSOD. CONCLUSIONS: German adolescents and young adults tend to be stable
      in the drinking states of abstinence, use of alcohol, risky single-occasion
      drinking and frequent risky single-occasion drinking. Females are less likely to
      transition to riskier states and more likely to transition back from frequent
      risky single-occasion drinking, higher age is associated with lower hazard of
      transitioning and participants of higher socio-economic status are less likely to
      transition from 'use of alcohol' to 'risky single-occasion drinking'.

PMID- 25959143
TI  - 25-gauge pars plana vitrectomy with medium-term postoperative perfluoro-n-octane
      for the repair of giant retinal tears.
AB  - PURPOSE: The purpose of this study was to describe the treatment of giant retinal
      tears (GRTs) with 25-gauge pars plana vitrectomy (PPV) and medium-term
      postoperative perfluoro-n-octane (MT-PFO). METHODS: The study was a retrospective
      interventional case series of consecutive patients with GRTs treated with 25
      gauge PPV and postoperative MT-PFO for a period of 2-3 weeks. A second, staged
      procedure was performed in all patients for PFO removal. RESULTS: Twenty-three
      eyes of 22 patients were studied, with a mean follow-up of 33.04 +/- 19.74
      months. Successful reattachment was achieved in 91.3 % of eyes (21/23) after MT
      PFO. Retinal re-detachment occurred in five eyes, which was caused by
      proliferative vitreoretinopathy. Additional complications included cataract
      progression (n = 10), foreign body response (30.4 %, 7/23), and transient
      intraocular pressure (IOP) elevation (8/23, 34.8 %). Transient IOP elevation was
      associated with worse visual outcome (p = 0.01). CONCLUSIONS: MT-PFO was found to
      be an effective and safe technique for operative management of GRTs. In the
      majority of patients, retinas remained attached without further surgical
      intervention. Cataract progression, intraocular inflammation, and associated
      increased intraocular pressure are potential complications of MT-PFO.

PMID- 25959144
TI  - Histological variant as the significant predictor of survival in patients with
      lymph node positive urothelial carcinoma of the bladder.
AB  - The aim of this study was to evaluate the impact of histological variants of
      urothelial carcinoma (UC) on survival outcomes in patients with lymph node (LN)
      positive UC of the bladder. We reviewed and analyzed the clinical data from 424
      patients who underwent radical cystectomy (RC) with pelvic lymph node dissection
      (PLND) for UC of the bladder and who did not receive neoadjuvant chemotherapy in
      our institution between 1991 and 2012. In total, 92 patients (21.7%) had
      histologically confirmed LN positive disease. In the LN negative group (332
      patients), histological variants of UC were not a significant predictor in
      univariate analysis. However, in the LN positive group, histological variants of
      UC were a significant independent prognostic factor of overall survival (hazard
      ratio (HR) 3.54; 95% confidence interval (CI) 1.77-7.08, p < 0.001) and cancer
      specific survival (HR 3.66; 95% CI 1.69-7.90, p = 0.001) in both uni-variate and
      multivariate Cox regression analyses. The presence of histological variants of UC
      may indicate a worse prognosis in LN positive patients after RC with PLND for UC
      of the bladder and more aggressive adjuvant therapy may be required for the
      improvement of postoperative survival. 

PMID- 25959146
TI  - Quality and safety: reflection on the implications for critical care nursing
      education.
AB  - BACKGROUND: Safe and high quality health care is underpinned by health care
      professionals possessing the knowledge, skills and professional attributes which
      are necessary for their specific clinical speciality and area of practice.
      Education is crucial as it enables clinicians to learn and put into practice
      their specialist knowledge, skills and attributes. These elements will be based
      on clinical standards, which set the agenda for quality and safety in health
      care. AIM: The purpose of this paper is to reflect upon how a post-registration,
      degree-level critical care nursing course provided by an English university
      facilitates nurses to deliver high quality, safe nursing care for critically ill
      patients and their families. METHODS: As a reflective analysis, the process of
      reflection will be guided and structured according to Rolfe's framework for
      reflective practice. The reflection is based upon the personal observations and
      teaching experiences of two university lecturers involved in the delivery of the
      critical care course. CONCLUSIONS: Critical care nursing education can
      incorporate informed practice, simulation and non-technical skills into post
      registration critical-care nursing courses as a way of promoting high-quality,
      safe clinical practice in the critical care setting. This article provides
      examples from one course's experience with doing this and ends with specific
      recommendations for how critical care nursing courses can enhance further the
      promotion of quality and safety. RELEVANCE TO CLINICAL PRACTICE: Educators,
      mentors and students of post-registration critical care nursing courses are
      encouraged to explore the relevance of nursing education in promoting safe and
      high-quality clinical practice.

PMID- 25959145
TI  - Epicardial adipose tissue has a unique transcriptome modified in severe coronary
      artery disease.
AB  - OBJECTIVE: To explore the transcriptome of epicardial adipose tissue (EAT) as
      compared to subcutaneous adipose tissue (SAT) and its modifications in a small
      number of patients with coronary artery disease (CAD) versus valvulopathy.
      METHODS: SAT and EAT samples were obtained during elective cardiothoracic
      surgeries. The transcriptome of EAT was evaluated, as compared to SAT, using an
      unbiased, whole-genome approach in subjects with CAD (n = 6) and without CAD (n =
      5), where the patients without CAD had cardiac valvulopathy. RESULTS: Relative to
      SAT, EAT is a highly inflammatory tissue enriched with genes involved in
      endothelial function, coagulation, immune signaling, potassium transport, and
      apoptosis. EAT is lacking in expression of genes involved in protein metabolism,
      tranforming growth factor-beta (TGF-beta) signaling, and oxidative stress.
      Although underpowered, in subjects with severe CAD, there is an expression trend
      suggesting widespread downregulation of EAT encompassing a diverse group of gene
      sets related to intracellular trafficking, proliferation/transcription
      regulation, protein catabolism, innate immunity/lectin pathway, and ER stress.
      CONCLUSIONS: The EAT transcriptome is unique when compared to SAT. In the setting
      of CAD versus valvulopathy, there is possible alteration of the EAT transcriptome
      with gene suppression. This pilot study explores the transcriptome of EAT in CAD
      and valvulopathy, providing new insight into its physiologic and pathophysiologic
      roles.

PMID- 25959147
TI  - Sandwich-structured graphene-nickel silicate-nickel ternary composites as
      superior anode materials for lithium-ion batteries.
AB  - We report the synthesis of sandwich-structured graphene-nickel silicate-Ni
      ternary composites by using the solvothermal method followed by a simple in situ
      reduction procedure. The composites show an interesting structure with graphene
      sandwiched between two layers of well-dispersed Ni nanoparticles (NPs) anchored
      on ultrathin nickel silicate nanosheets. These ternary composites exhibit
      enhanced performance as anode materials owing to the synergistic effect between
      the graphene matrix and electrochemically inert Ni nanoparticles, an effect that
      holds promise for the design and fabrication of other advanced electrode
      materials. 

PMID- 25959148
TI  - Self-collected buccal swabs and rapid, real-time PCR during a large measles
      outbreak in Wales: Evidence for the protective effect of prior MMR immunisation.
AB  - BACKGROUND: We describe the laboratory response to a large measles outbreak that
      occurred during 2012-2013 centred in mid and west Wales, UK. OBJECTIVES: To
      demonstrate the impact of rapid measles testing on the management of a large
      outbreak, to show the complex molecular epidemiology and determine the role of
      previous MMR immunisation on a large cohort of exposed people. STUDY DESIGN:
      Results from oral fluid antibody testing and self-collected buccal swabs tested
      by real-time PCR were reconciled and analysed to determine level of agreement and
      to calculate MMR vaccine efficacy during the outbreak. RESULTS: During the
      outbreak 1435 notifications of measles were received from across Wales. Samples
      were received from 70% of notified cases with a positivity rate of 56% within the
      outbreak compared to 15% for the rest of Wales. Measles RNA was detected in 53
      cases with previous history of MMR immunisation, but viral loads were lower than
      those detected in unimmunised cases. The molecular epidemiology showed at least
      two distinct D8 strains of measles virus were introduced into Wales along with a
      separate introduction of a B3 strain outside the outbreak area. CONCLUSION:
      Molecular testing of all notified measles cases offers the most rapid way of
      confirming the introduction of measles into a population potentially before
      secondary transmission has already occurred. The outbreak data confirms the
      protective effect of the MMR vaccine with vaccine efficacy calculated at 96% for
      one dose and 99% for two doses supporting the WHO recommendations for a two dose
      MMR immunisation schedule.

PMID- 25959149
TI  - Respiratory viruses in airline travellers with influenza symptoms: Results of an
      airport screening study.
AB  - BACKGROUND: There is very little known about the prevalence and distribution of
      respiratory viruses, other than influenza, in international air travellers and
      whether symptom screening would aid in the prediction of which travellers are
      more likely to be infected with specific respiratory viruses. OBJECTIVES: In this
      study, we investigate whether, the use of a respiratory symptom screening tool at
      the border would aid in predicting which travellers are more likely to be
      infected with specific respiratory viruses. STUDY DESIGN: Data were collected
      from travellers arriving at Christchurch International Airport, New Zealand,
      during the winter 2008, via a symptom questionnaire, temperature testing, and
      respiratory sampling. RESULTS: Respiratory viruses were detected in 342 (26.0%)
      of 1313 samples obtained from 2714 symptomatic travellers. The most frequently
      identified viruses were rhinoviruses (128), enteroviruses (77) and influenza B
      (48). The most frequently reported symptoms were stuffy or runny nose (60%),
      cough (47%), sore throat (27%) and sneezing (24%). Influenza B infections were
      associated with the highest number of symptoms (mean of 3.4) followed by
      rhinoviruses (mean of 2.2) and enteroviruses (mean of 1.9). The positive
      predictive value (PPV) of any symptom for any respiratory virus infection was low
      at 26%. CONCLUSIONS: The high prevalence of respiratory virus infections caused
      by viruses other than influenza in this study, many with overlapping symptotology
      to influenza, has important implications for any screening strategies for the
      prediction of influenza in airline travellers.

PMID- 25959150
TI  - A heart breaking case of rapidly developing severe hemophagocytic syndrome
      secondary to chronic active EBV infection; a case report and review of the
      literature.
AB  - Epstein-Barr virus (EBV, HHV-4) is a gamma Herpesvirus with a 90% >seroprevalence
      in adults. Reactivations in non-immuno compromised individuals usually cause mild
      or no symptoms at all. Rarely, host immunity-virus balance is interrupted,
      resulting in a chronic active EBV infection. The following case illustrates the
      rapid development of severe hemophagocytic syndrome during chronic active EBV
      infection in a 73 year old woman who presented with lower extremity pain and
      edema, splenomegaly and abnormal liver enzymes. A diagnosis of chronic active EBV
      infection was made following an extensive investigation and the patient died
      secondary to rapidly progressive hemophagocytic syndrome. 

PMID- 25959152
TI  - Association of hepatitis E virus and essential cryoglobulinemia?

PMID- 25959151
TI  - Neuraminidase inhibitor therapy in a military population.
AB  - BACKGROUND: Although neuraminidase inhibitors (NI) are the mainstay of treatment
      for influenza infection, prescribing practice for these agents is not well
      described. Additionally, benefit is contested. OBJECTIVES: We examined provider
      prescriptions of NI during the 2009 pandemic and post-pandemic periods. We also
      evaluated the effectiveness of NI in reducing severity of influenza infection.
      STUDY DESIGN: Data on NI prescription and severity of influenza infection were
      compiled in healthy pediatric and adult beneficiaries enrolled in a prospective
      study of influenza like illness conducted at five military medical centers over
      five years. Subjects underwent nasal swabs to determine viral etiology of their
      infection. Demographic, medication and severity data were collected. Subjects
      with positive influenza were included. RESULTS: Two hundred sixty three subjects
      were influenza positive [38% [H1N1] pdm09, 38.4% H3N2, and 20.5% B); 23.9% were
      treated with NI. NI were initiated within 48h in 63% of treated subjects.
      Although NI use increased over the five years of the study, early use declined.
      Most measures for severity of illness were not significantly reduced with NI;
      adults treated within 48h had only a modest reduction in duration and severity of
      some of their symptoms. CONCLUSIONS: NI use in our population is increasing, but
      early use is not. NI use resulted in no reduction in complications of illness.
      Resolution of symptoms and reduction in severity of some symptoms were slightly
      better in adults who were treated early. These modest benefits do not support
      routine treatment with NI in otherwise healthy individuals with influenza.

PMID- 25959153
TI  - CCHF virus variants in Pakistan and Afghanistan: Emerging diversity and
      epidemiology.
AB  - BACKGROUND: Crimean Congo hemorrhagic fever (CCHF) has been reported from more
      than 30 countries in Africa, Asia, Eastern Europe and Middle East. The disease is
      considered endemic in Pakistan and neighboring countries like Iran and
      Afghanistan. OBJECTIVES: This study aimed to explore the genetic diversity of
      CCHF virus (CCHFV) detected in Pakistan and Afghanistan based on analysis of
      partial S-segment sequences. STUDY DESIGN: During 2011, one hundred samples
      satisfying the CCHF case definition were tested by (ELISA) and RT-PCR for
      detection of IgM antibodies and viral RNA, respectively. Phylogenetic analysis
      was carried out on partial S-segment nucleotide sequences using MEGA 5.0.
      RESULTS: Out of one hundred collected during 2011, 49 (49%) were positive for
      CCHF either by ELISA/RT-PCR or both. The mean age of the CCHFV positive cases was
      30.32 years (range 18-56 years) and overall mortality rate was 20.4%. All CCHF
      virus isolates from this study clustered with strains previously reported from
      Pakistan, Iran and Afghanistan within the Asia-1 genogroup. Four distinct sub
      clades were found circulating within Asia-1 genogroup. Six CCHFV strains found in
      Pakistan and Afghanistan grouped into a new sub-clade-D. CONCLUSIONS: Data from
      this study shows that endemic foci of CCHFV span the international border between
      Pakistan and Afghanistan with genetically diverse variants circulating in this
      region. Our findings emphasize to establish a laboratory based surveillance
      program and devise health policy measures to control CCHF infection especially in
      Baluchistan.

PMID- 25959154
TI  - Occult infection with HBV intergenotypic A2/G recombinant following acute
      hepatitis B caused by an HBV/A2 isolate.
AB  - Viral and host factors leading to occult hepatitis B virus (HBV) infection (OBI)
      are not fully understood. Whether HBV genotype may influence the occurrence and
      course of OBIs is unknown. Here, we describe the case of a patient infected with
      HBV genotype A2 who developed symptomatic acute hepatitis and did not seroconvert
      after loss of HBsAg and HBeAg. The acute phase of hepatitis B was followed by a
      period of more than 2 years during which the DNA of an intergenotypic HBV/A2/G
      recombinant was intermittently detected in serum. 

PMID- 25959155
TI  - Difficulties of interpretation of Zaire Ebola Virus PCR results and implication
      in the field.

PMID- 25959156
TI  - Persistent rhinovirus infection in pediatric hematopoietic stem cell transplant
      recipients with impaired cellular immunity.
AB  - BACKGROUND: HRV infections are generally self-limiting in healthy subjects,
      whereas in immunocompromised hosts HRV infections can lead to severe
      complications and persistent infections. The persistence of HRV shedding could be
      due to the inefficient immunological control of a single infectious episode.
      OBJECTIVES: To investigate the clinical, virologic and immunologic
      characteristics of pediatric HSCT recipients with HRV-PI infection. STUDY DESIGN:
      During the period 2006-2012, eight hematopoietic stem cell transplant (HSCT)
      recipients presented with persistent rhinovirus infection (HRV-PI, >=30 days).
      Viral load and T-CD4(+), T-CD8(+), B and NK lymphocyte counts at the onset of
      infection were compared with those of fourteen HSCT recipients with acute HRV
      infection (HRV-AI, <=15 days). RESULTS: The median duration of HRV positivity in
      patients with HRV-PI was 61 days (range 30-174 days) and phylogenetic analysis
      showed the persistence of a single HRV type in all patients (100%). In HSCT
      recipients with HRV-PI, T-CD4(+), T-CD8(+) and NK cell counts at the onset of
      infection were significantly lower than those observed in recipients with HRV-AI
      (p<0.01), while B cell counts were similar in the two groups (p= 0.25). A
      decrease in HRV load was associated with a significant increase in T-CD4(+), T
      CD8(+)and NK lymphocyte counts in HRV-PI patients (p<0.01). CONCLUSIONS: This
      study suggests a role for cellular immunity in HRV clearance and highlights the
      importance of its recovery for the control of HRV infection in HSCT recipients.

PMID- 25959157
TI  - Diagnostic performance of near-patient testing for influenza.
AB  - BACKGROUND: Rapid diagnosis of influenza is important for controlling outbreaks
      and starting antiviral therapy. Direct antigen detection (DAD) is rapid, but
      lacks sensitivity, whereas nucleic acid amplification testing (NAT) is more
      sensitive, but also more time-consuming. OBJECTIVES: To evaluate the performance
      of a rapid isothermal NAT and two DADs. STUDY DESIGN: During February-May 2014,
      we tested 211 consecutive patients with influenza-like illness using a commercial
      isothermal NAT (AlereTM Influenza A&B) as well as the DAD Sofia((r)) Influenza
      A+B and BinaxNOW((r)) Influenza A&B for detection of influenza-A and -B virus.
      RespiFinder-22((r)) a commercial multiplex NAT served as reference test. Serial
      10-fold dilutions of influenza-A and -B cell culture supernatants were examined.
      Another 225 patient samples were tested during December 2014-February 2015.
      RESULTS: Compared to RespiFinder-22((r)), the isothermal NAT AlereTM Influenza
      A&B, and the DAD Sofia((r)) Influenza A+B and BinaxNOW((r)) Influenza A&B had
      sensitivities of 77.8%, 59.3% and 29.6%, and specificities of 99.5%, 98.9% and
      100%, respectively, for the first 211 patient samples. AlereTM Influenza A&B
      showed 85.7% sensitivity and 100% specificity in the second cohort. Isothermal
      NAT was 10-100-fold more sensitive compared to DAD for influenza virus culture
      supernatants with a lower limit of detection of 5000-50,000 copies/mL. The
      average turn-around time (TAT) of isothermal NAT and DADs was 15min, but
      increased to 110min for AlereTM Influenza A&B, 30min for BinaxNOW((r)) Influenza
      A&B, and 45min for Sofia((r)) Influenza A+B, when analyzing batches of 6 samples.
      CONCLUSION: Simple sample processing and a TAT of 15min render isothermal NAT
      AlereTM Influenza A&B suitable for sequential near-patient testing, but the TAT
      advantage is lost when testing of larger series.

PMID- 25959158
TI  - Prevalence of beta and gamma human papillomaviruses in the anal canal of men who
      have sex with men is influenced by HIV status.
AB  - BACKGROUND: Mucosal high-risk human papillomavirus (HPV) types benefit
      differently from the immunocompromised status of the host. So far it is not known
      whether a similar scenario holds for the large group of the beta and gamma
      cutaneous HPV types that appear to be present at several anatomical sites.
      METHODS: The presence of beta (n=43) and gamma (n=30) HPVs in the anal samples of
      66 HIV-positive and 153 HIV-negative anonymized men who have sex with men (MSM)
      was determined by multiplex PCR, using type-specific primers and bead-based
      hybridization (Luminex technology). RESULTS: The prevalence of beta and gamma HPV
      infection was 65.6% and 68.2%, respectively, among HIV-positive MSM and 59.1% and
      57.7%, respectively, among HIV-negative MSM. beta-2 and gamma-10 were found to be
      the most prevalent species in both groups. The prevalence of infection with HPV
      types of the species beta-1 (P=0.02), beta-3 (P=0.002), gamma-6 (P=0.002), and
      gamma-7 (P=0.02) was higher in HIV-positive than HIV-negative men. In contrast,
      the beta-2 species was equally distributed in the two groups, while the gamma-10
      species was slightly affected by HIV status. CONCLUSIONS: These findings provide
      evidence that impairment of the host's immune surveillance impacts beta and gamma
      HPV infections differently.

PMID- 25959159
TI  - A non-fatal case of hantavirus cardiopulmonary syndrome imported into the UK (ex
      Panama), July 2014.

PMID- 25959160
TI  - Development and evaluation of a real-time EBOV-L-RT-qPCR for detection of Zaire
      ebolavirus.
AB  - An RT-qPCR targeting EBOV-L including the preceding RNA extraction protocol were
      set up and evaluated. 

PMID- 25959161
TI  - Comparing triage algorithms using HPV DNA genotyping, HPV E7 mRNA detection and
      cytology in high-risk HPV DNA-positive women.
AB  - BACKGROUND: High-risk human papillomavirus (hrHPV) DNA positive women require
      triage testing to identify those with high-grade cervical intraepithelial
      neoplasia or cancer (>=CIN2). OBJECTIVE: Comparing three triage algorithms (1) E7
      mRNA testing following HPV16/18/31/33/45/52/58 genotyping (E7 mRNA test), (2)
      HPV16/18 DNA genotyping and (3) cytology, for >=CIN2 detection in hrHPV DNA
      positive women. STUDY DESIGN: hrHPV DNA-positive women aged 18-63 years visiting
      gynecology outpatient clinics were included in a prospective observational cohort
      study. From these women a cervical scrape and colposcopy-directed biopsies were
      obtained. Cervical scrapes were evaluated by cytology, HPV DNA genotyping by bead
      based multiplex genotyping of GP5+6+-PCR-products, and presence of
      HPV16/18/31/33/45/52/58 E7 mRNA using nucleic acid sequence-based amplification
      (NASBA) in DNA positive women for respective HPV types. Sensitivities and
      specificities for >=CIN2 were compared between E7 mRNA test and HPV16/18 DNA
      genotyping in the total group (n=348), and E7 mRNA test and cytology in a
      subgroup of women referred for non-cervix-related gynecological complaints
      (n=133). RESULTS: Sensitivity for >=CIN2 of the E7 mRNA test was slightly higher
      than that of HPV16/18 DNA genotyping (66.9% versus 60.9%; ratio 1.10, 95% CI:
      1.0002-1.21), at similar specificity (54.8% versus 52.3%; ratio 1.05, 95% CI:
      0.93-1.18). Neither sensitivity nor specificity of the E7 mRNA test differed
      significantly from that of cytology (sensitivity: 68.8% versus 75.0%; ratio 0.92,
      95% CI: 0.72-1.17; specificity: 59.4% versus 65.3%; ratio 0.91, 95% CI: 0.75
      1.10). CONCLUSION: For detection of >=CIN2 in hrHPV DNA-positive women, an
      algorithm including E7 mRNA testing following HPV16/18/31/33/45/52/58 DNA
      genotyping performs similar to HPV16/18 DNA genotyping or cytology.

PMID- 25959162
TI  - Evaluation of the COBAS((r)) AmpliPrep/COBAS((r)) TaqMan((r)) HCV Test, v2.0 and
      comparison to assays used in routine clinical practice in an international
      multicenter clinical trial: The ExPECT study.
AB  - BACKGROUND: The COBAS((r)) AmpliPrep((r))/COBAS((r)) TaqMan((r)) HCV Test, v2.0
      (CAP/CTM2) is used for HCV RNA viral load monitoring. OBJECTIVES: The performance
      of the CAP/CTM2 was compared to other widely used tests, including a manual
      version of the assay (the COBAS((r)) TaqMan((r)) HCV Test, v2.0 for use with the
      High Pure System, HPS/CTM2) predominantly used during phase III clinical trials
      for the new direct acting antiviral therapies. STUDY DESIGN: Low HCV RNA level
      comparisons were performed across tests (Abbott Realtime HCV Test, ART;
      COBAS((r)) AmpliPrep((r))/COBAS((r)) TaqMan((r)) HCV Test, v1.0, CAP/CTM1;
      CAP/CTM2; and HPS/CTM2) using dilutions of the 2nd HCV WHO International
      Standard. Additionally, the clinical performance of the CAP/CTM2 was evaluated
      with 421 leftover HCV RNA-positive routine clinical samples. RESULTS: All
      quantifiable WHO dilutions were within +/-0.3log10IU/mL of the expected results
      across tests and the analytical sensitivity resulted in a limit of detection of
      12IU/mL (95% confidence interval, 10, 15). When clinical samples were tested the
      results for 87% (367 of 421) of all sample comparisons were within +/
      0.5log10IU/mL. When low viral load results (25-3500IU/mL) were compared, values
      obtained by the ART assay were significantly lower (p<0.0001) than those obtained
      with the CAP/CTM2. CONCLUSIONS: The new CAP/CTM2 showed good accuracy with
      comparable sensitivity to comparator assays. The new kit is well-suited for use
      in the routine diagnostic laboratory, especially for accurate monitoring of
      patients receiving triple therapy or interferone-free regimens.

PMID- 25959163
TI  - HCV-specific lymphocyte responses in individuals with positive anti-HCV but
      negative HCV-RNA.
AB  - BACKGROUND: Hepatitis C virus (HCV) status cannot be reliably predicted in anti
      HCV positive/HCV-RNA negative individuals who may either have recovered
      spontaneously or have a false-positive test due to antibody cross-reaction.
      Investigating T lymphocyte responses in individuals with different HCV status may
      help understand the cellular immune mechanisms underlying spontaneous recovery,
      treatment response, and chronicity. OBJECTIVE: We aimed to determine whether anti
      HCV positive, HCV-RNA negative individuals are truly spontaneous recoverers from
      acute HCV infection. STUDY DESIGN: We used enzyme-linked immunosorbent spot
      (ELISPOT) assay to compare HCV-specific lymphocyte response among anti-HCV
      positive/HCV-RNA negative individuals, patients with sustained virological
      response to interferon-gamma/ribavirin treatment, and patients with chronic HCV
      infection. RESULTS: We found that 83% of anti-HCV positive/HCV-RNA negative
      individuals without a past medical history of acute icteric hepatitis had an HCV
      specific T lymphocyte response in peripheral blood. Lymphocyte responses in these
      individuals were similar in magnitude to treatment responders unlike patients
      with chronic HCV whose virus-directed immunity was significantly suppressed.
      CONCLUSIONS: Detection of HCV-specific T lymphocyte responses using ELISPOT is a
      feasible method to ascertain past asymptomatic acute HCV infection.

PMID- 25959164
TI  - Serological evidence of equine influenza infections among persons with horse
      exposure, Iowa.
AB  - BACKGROUND: Equine influenza virus (EIV) is considered enzootic in North America
      and experimental studies have documented human EIV infections. STUDY DESIGN: This
      cross-sectional study examined 94 horse-exposed and 34 non-exposed controls for
      serological evidence of EIV infection. Sera were evaluated for antibodies against
      three EIV and two human H3N2 viruses using microneutralization (MN),
      neuraminidase inhibition (NI), enzyme-linked lectin (ELLA), and hemagglutination
      inhibition (HI) serological assays. Risk factor analyses were conducted using
      logistic regression and proportional odds modeling. RESULTS: There was evidence
      of previous infection by MN assay against A/equine/Ohio/2003(H3N8) but not the
      other 2 EIVs. Eleven (11.7%, maximum titer 1:320) horse-exposed and 2 (5.9%,
      maximum titer 1:160) control subjects had MN titers >=1:80. Among the horse
      exposed, 18 (19.1%) were positive by NI assay and 8 (8.5%) had elevated ELLA
      titers >=1:10. Logistic regression modeling among horse-exposed revealed that
      having an elevated MN or ELLA titer (<=1:10) was associated with having a
      positive NI titer (OR=4.9; 95% CI=1.3-18.7, and OR=53.2; 95% CI=5.9-478.5,
      respectively). Upon proportional odds modeling, having worked as an equine
      veterinarian (OR=14.0; 95% CI=2.6-75.9), having a history of smoking (OR=3.1; 95%
      CI=1.2-7.7), and receipt of seasonal influenza vaccine between 2000 and 2005
      (OR=2.3; 95% CI=1.1-5.0) were important independent risk factors for elevations
      in MN assay. CONCLUSIONS: While we cannot rule out confounding exposures, these
      data support the premise that occupational exposure to EIV may lead to human
      infection.

PMID- 25959165
TI  - Intranasal dexmedetomidine for sedation in children undergoing transthoracic
      echocardiography study--a prospective observational study.
AB  - BACKGROUND: Intranasal dexmedetomidine has been used for sedation in children
      undergoing nonpainful procedures. OBJECTIVE: The aim of this study was to
      determine the success rate of intranasal dexmedetomidine sedation for children
      undergoing transthoracic echocardiography examination. METHODS: This was a
      prospective observational study of 115 children under the age of 3 years
      undergoing echocardiography examination under sedation with intranasal
      dexmedetomidine at 3 mcg.kg(-1). RESULTS: Of the 115 children, 100 (87%) had
      satisfactory sedation with intranasal dexmedetomidine. The mean onset time was
      16.7 +/- 7 min (range 5-50 min). The mean wake up time was 44.3 +/- 15.1 min
      (range 12-123 min). The wake up time was significantly correlated with duration
      of procedure with R = 0.540 (P < 0.001). Aside from one patient who required
      oxygen supplementation, all children in this investigation had an acceptable
      heart rate and blood pressure and required no medical intervention. CONCLUSION:
      Sedation by intranasal dexmedetomidine at 3 mcg.kg(-1) is associated with
      acceptable success rate in children undergoing echocardiography with no adverse
      events in this cohort.

PMID- 25959166
TI  - Patterns of Clinical Recurrence of Node-positive Prostate Cancer and Impact on
      Long-term Survival.
AB  - BACKGROUND: The patterns of recurrence of patients with node-positive prostate
      cancer (PCa) at radical prostatectomy (RP) are still unknown. OBJECTIVE: To
      describe recurrence patterns, to identify predictors of progression, and to test
      the impact of the site of clinical recurrence (CR) on cancer-specific mortality
      (CSM). DESIGN, SETTING, AND PARTICIPANTS: We included 1003 patients with node
      positive PCa treated with RP and extended pelvic lymph node dissection. Patients
      who experienced biochemical recurrence (BCR; n=370) and CR (n=183) were
      identified. CR was defined as positive imaging after BCR. Patients were
      stratified according to the first site of CR: local and/or nodal (recurrence in
      the prostatic bed and/or pelvic nodes), retroperitoneal, bony, or visceral.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable competing-risks
      regression analyses identified predictors of systemic recurrence (ie,
      retroperitoneal, bony, and/or visceral) and tested the association between the
      site of recurrence and CSM after accounting for the risk of other-cause
      mortality. RESULTS AND LIMITATIONS: When considering patients experiencing BCR,
      pathologic Gleason score, time to BCR, and the administration of a positron
      emission tomography/computed tomography scan represented predictors of systemic
      recurrence (all p <= 0.002). Among patients who experienced CR, recurrence was
      local and/or nodal in 56 (30.5%), retroperitoneal in 25 (13.7%), skeletal in 77
      (42.1%), and visceral in 25 (13.7%). Among patients experiencing local
      recurrence, 27 (48.2%) had positive margins, 29 (51.8%) had adjuvant
      radiotherapy, and 22 (39.5%) had salvage radiotherapy. Patients experiencing
      local and/or nodal recurrence had higher 5-yr CSM-free survival rates compared
      with those with retroperitoneal, skeletal, and visceral recurrence (79.3%, 76.3%,
      50.8%, and 35.3%, respectively; p<0.001). The site of recurrence represented an
      independent predictor of CSM (p <= 0.04). CONCLUSIONS: In approximately one-third
      of patients who are pN+ and experience CR, the prostatic bed and pelvic lymph
      nodes represent the first sites of recurrence. These patients have a more
      favorable prognosis compared with those with skeletal and visceral metastases.
      These data have important implications for the selection of the optimal
      postoperative management of pN+ patients who experience CR. Although patients
      with local and/or pelvic nodal recurrence might benefit from nonsystemic salvage
      therapies, men with visceral and skeletal recurrence might represent ideal
      candidates for systemic approaches. PATIENT SUMMARY: Not all patients with pN+
      prostate cancer who experience clinical recurrence harbor distant metastatic
      disease. Local and/or nodal recurrence occurs in one-third of these cases. These
      patients share a more favorable prognosis than their counterparts with systemic
      recurrence. These results are important for tailoring the optimal postoperative
      management for each node-positive patient with recurrent disease after surgery.

PMID- 25959167
TI  - Screening for cancer: lessons learned from the prostate, lung, colorectal, and
      ovarian cancer screening trial.
AB  - While the PLCO Cancer Screening trial demonstrated no observed mortality benefit
      associated with screening for prostate cancer with prostate-specific antigen and
      rectal exam, the knowledge gained about prostate cancer and screening and
      resources developed in completing the trial make the trial a success. 

PMID- 25959168
TI  - Soft tissue middle ear mass. Vestibular schwannoma.

PMID- 25959169
TI  - A microscale method of protein extraction from bacteria: Interaction of
      Escherichia coli with cationic microparticles.
AB  - We developed a simple, highly selective, efficient method for extracting
      recombinant proteins from Escherichia coli. Our recombinant protein yield was
      equivalent to those obtained with high pressure homogenization, and did not
      require exposure to harsh thermal, chemical, or other potentially denaturing
      factors. We first ground conventional resin, designed for the exchange of small
      anions, into microparticles about 1MUm in size. Then, these cationic
      microparticles were brought convectively into close contact with bacteria, and
      cell membranes were rapidly perforated, but solid cell structures were not
      disrupted. The released soluble components were adsorbed onto the cell wall
      associated microparticles or diffused directly into the supernatant.
      Consequently, the selective adsorption and desorption of acidic molecules is
      built into our extraction method, and replaces the equally effective subsequent
      capture on anion exchange media. Simultaneously to cell perforation flocculation
      was induced by the microparticles facilitating separation of cells yet after
      desorption of proteins with NaCl. Relative to high pressure homogenization,
      endogenous component release was reduced by up to three orders of magnitude,
      including DNA, endotoxins, and host cell proteins, particularly outer membrane
      protein, which indicates the presence of cell debris. 

PMID- 25959171
TI  - A new, integrated, continuous purification process template for monoclonal
      antibodies: Process modeling and cost of goods studies.
AB  - An evolving biopharmaceutical industry requires advancements in biomanufacturing
      that offer increased productivity and improved economics without sacrificing
      process robustness. Accordingly, we have developed a new monoclonal antibody
      purification template comprised of flocculation-based clarification, capture by
      continuous multi-column protein A chromatography and flow-through polishing. The
      new process offers a robust, single-use manufacturing solution while
      significantly reducing overall cost of goods. Modeling studies verify that the
      individual clarification, capture and polishing solutions offer significant
      advantages as stand-alone unit operations. These technologies were also designed
      to be integrated into a continuous purification template. Process modeling
      studies have been used to highlight both cost and operational advantages of the
      new process template. Depending on scale, savings of more than 20% and 60% were
      seen for commercial and clinical operation, respectively. Integrating the
      technologies into a continuous process consistently offered additional cost
      advantages. During template development, process modeling was instrumental in
      highlighting the importance of identifying technologies that provided high
      product yield and purification factors. Additionally, high product concentration
      and eliminating the need for intermediate product dilution emerged as important
      considerations for newly developed unit operations. Combining experimental work
      with insights from modeling can significantly improve the outcome of product and
      process development. 

PMID- 25959170
TI  - Complete genome sequence of Paenibacillus riograndensis SBR5(T), a Gram-positive
      diazotrophic rhizobacterium.
AB  - Paenibacillus riograndensis is a Gram-positive rhizobacterium which exhibits
      plant growth promoting activities. It was isolated from the rhizosphere of wheat
      grown in the state of Rio Grande do Sul, Brazil. Here we announce the complete
      genome sequence of P. riograndensis strain SBR5(T). The genome of P.
      riograndensis SBR5(T) consists of a circular chromosome of 7,893,056bps. The
      genome was finished and fully annotated, containing 6705 protein coding genes, 87
      tRNAs and 27 rRNAs. The knowledge of the complete genome helped to explain why P.
      riograndensis SBR5(T) can grow with the carbon sources arabinose and mannitol,
      but not myo-inositol, and to explain physiological features such as biotin
      auxotrophy and antibiotic resistances. The genome sequence will be valuable for
      functional genomics and ecological studies as well as for application of P.
      riograndensis SBR5(T) as plant growth-promoting rhizobacterium. 

PMID- 25959172
TI  - Predicting survival after surgery: a matter of life and death.

PMID- 25959173
TI  - 'Mainstreaming' of less than full-time training.

PMID- 25959174
TI  - Reviews, systematic reviews and Anaesthesia.

PMID- 25959175
TI  - Validation of long-term survival prediction for scheduled abdominal aortic
      aneurysm repair with an independent calculator using only pre-operative
      variables.
AB  - We observed survival after scheduled repair of abdominal aortic aneurysm in 1096
      patients for a median (IQR [range]) of 3.0 (1.5-5.8 [0-15]) years: 943 patients
      had complete data, 250 of whom died. We compared discrimination and calibration
      of an external model with the Kaplan-Meier model generated from the study data.
      Integrated Brier misclassification scores for both models at 1-5 postoperative
      years were 0.04, 0.08, 0.11, 0.13 and 0.16, respectively. Harrel's concordance
      index at 1-5 postoperative years was 0.73, 0.71, 0.68, 0.67 and 0.66,
      respectively. Groups with median 5-year predicted mortality of 40% (n = 251), 18%
      (n = 414) and 8% (n = 164) had lower observed mortality than 114 patients with
      70% predicted mortality, hazard ratio (95% CI): 0.58 (0.37-0.76), p = 0.0031;
      0.30 (0.19-0.48), p = 1.7 * 10(-12) and 0.19 (0.13-0.27), p = 1.3 * 10(-10) ,
      respectively, test for trend p = 5.6 * 10(-15) . Survival predicted by the
      external calculator was similar to the Kaplan-Meier estimate. 

PMID- 25959176
TI  - Simulations of the effects of scheduled abdominal aortic aneurysm repair on
      survival.
AB  - I simulated survival with and without scheduled repair of abdominal aortic
      aneurysms with different diameters in different populations. The results imply
      that scheduled repair should be determined by the combination of a patient's
      monthly mortality hazard and aneurysm diameter. The median survival of some
      patients will be extended by the scheduled repair of aneurysms smaller than 55
      mm, whereas the median survival of other patients will be curtailed by repair of
      any aneurysm. The results also suggest that, on average, surveillance is futile:
      the effect of scheduled aneurysm repair on an individual's median survival did
      not change but the cohort effect diminished as patients died during surveillance.
      The results of the U.K. Small Aneurysm Study were reproduced in simulation and
      are compatible with the repair of aneurysms smaller than 55 mm diameter.
      Epidemiological simulations suggest that past randomised controlled trials
      underestimate the effect of aneurysm repair today.

PMID- 25959177
TI  - Influence of less than full-time or full-time on totality of training and
      subsequent consultant appointment in anaesthesia.
AB  - Changes in medical training have increased the popularity of less than full-time
      training. However, there are no data on the impact on training time or consultant
      workforce. We reviewed a three-year cohort of trainees via the Royal College of
      Anaesthetist's training and recruitment databases. Eighty-eight (96%) less than
      full-time trainees and 677 (95%) full-time trainees were appointed to a
      substantive consultant post (p = 0.82). Three (3%) less than full-time trainees
      and 12 (2%) full-time trainees gained part-time consultant posts (p < 0.001).
      Average length of training (years, months, days) was 8 y, 5 m, 6 d (median (IQR
      [range]) 5 y, 0 m, 14 d (4 y, 11 m, 29 d - 9 y, 8 m, 3 d [4 y, 2 m, 18 d - 12 y,
      0 m, 0 d]) for full-time and 10 y, 8 m, 23 d (median (IQR [range]) 7 y, 3 m, 28 d
      (6 y, 7 m, 24 d - 11 y, 1 m, 23 d [4 y, 11 m, 29 d - 11 y, 9 m, 10 d]) for less
      than full-time trainees. The average length of training for both groups is
      significantly longer than the seven years used in workforce planning. 

PMID- 25959178
TI  - Group and save traffic lights.

PMID- 25959179
TI  - 'Difficult airway' or 'airway made difficult'?

PMID- 25959180
TI  - Further components for the PHASE basic airway checklist.

PMID- 25959181
TI  - Coupling and complexity in airway management.

PMID- 25959182
TI  - Failure to THRIVE.

PMID- 25959183
TI  - THRIVE--atelectasis, hypercarbia and consent.

PMID- 25959184
TI  - Apnoeic oxygenation in noma patients.

PMID- 25959185
TI  - Survive, then THRIVE.

PMID- 25959186
TI  - A reply.

PMID- 25959187
TI  - Glycopyrronium and maternal hypotension.

PMID- 25959188
TI  - Paracetamol and unwanted 5-hydroxytryptamine interactions.

PMID- 25959189
TI  - Further benefits of cyanoacrylate glue for central venous catheterisation.

PMID- 25959190
TI  - Guaranteeing drug delivery during total intravenous anaesthesia.

PMID- 25959191
TI  - Use of ROTEM in major obstetric haemorrhage.

PMID- 25959192
TI  - A reply.

PMID- 25959193
TI  - Sensing the force during laryngoscopy.

PMID- 25959194
TI  - Starch and haemostasis.

PMID- 25959195
TI  - A reply.

PMID- 25959196
TI  - Celecoxib as an Adjuvant to Fluvoxamine in Moderate to Severe Obsessive
      compulsive Disorder: A Double-blind, Placebo-controlled, Randomized Trial.
AB  - INTRODUCTION: A growing body of evidence implicates inflammatory cascades in the
      pathophysiology of obsessive-compulsive disorder (OCD), making this pathway a
      target for development of novel treatments. METHODS: 50 outpatients with moderate
      to severe OCD participated in the trial, and underwent 10 weeks of treatment with
      either celecoxib (200 mg twice daily) or placebo as an adjuvant to fluvoxamine.
      Participants were investigated using Yale-Brown Obsessive Compulsive Scale (Y
      BOCS). The main outcome measure was to assess the efficacy of celecoxib in
      improving the OCD symptoms. RESULTS: General linear model repeated measures
      demonstrated significant effect for time * treatment interaction on the Y-BOCS
      total scores [F (1.38, 66.34)=6.91, p=0.005]. Kaplan-Meier estimation with log
      rank test demonstrated significantly more rapid response in the celecoxib group
      than the placebo group (p<0.001). There was no significant difference in adverse
      event frequencies between the groups. DISCUSSION: The results of the current
      study suggest that celecoxib could be a tolerable and effective adjunctive
      treatment for more rapid and more satisfying improvements in OCD symptoms.

PMID- 25959197
TI  - Clinical pictures in Pelizaeus-Merzbacher disease: a report of a case.

PMID- 25959198
TI  - Long-term Hemodialysis Corrects Left Ventricular Dyssynchrony in End-stage Renal
      Disease: A Study with Gated Technetium-99m Sestamibi Myocardial Perfusion Single
      photon Emission Computed Tomography.
AB  - INTRODUCTION: Left ventricular (LV) dyssynchrony is common in patients with end
      stage renal disease (ESRD), and echocardiographic assessment has shown that it
      can be improved by a single session of hemodialysis (HD). The aim of this study
      was to assess the effects of chronic HD on LV dyssynchrony in patients ESRD by
      means of gated technetium-99m sestamibi myocardial perfusion single-photon
      emission computed tomography (GSPECT) with phase analysis. MATERIALS AND METHODS:
      Twelve patients with ESRD underwent GSPECT and echocardiography before the start
      of long-term HD (baseline) and 3 months later. In addition, 7 control subjects
      matched for age and sex underwent GSPECT and echocardiography within a 2-month
      period. To evaluate LV dyssynchrony, both histogram bandwidth (HBW) and phase
      standard deviation (PSD) were determined with phase analysis of GSPECT images.
      The end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction
      were also measured with GSPECT, and the LV mass index (LVMI) was measured with
      echocardiography. The LV dyssynchrony, volume, function, and mass were compared
      among control subjects, patients with ESRD at baseline, and patients with ESRD
      after 3 months of chronic HD. RESULTS: The LV dyssynchrony, volume, and mass at
      baseline were significantly greater in patients with ESRD than in control
      subjects (HBW, 65.5 degrees +/-54.4 degrees  vs. 22.3 degrees +/-7.5 degrees ,
      P<0.05; PSD, 21.0 degrees +/-15.5 degrees  vs. 7.6 degrees +/-5.5 degrees ,
      P<0.05; EDV, 105.7+/-29.2 vs. 72.3+/-13.9 mL, P<0.05; ESV, 44.3+/-22.1 vs. 20.9+/
      10.3 mL, P<0.05; LVMI, 136.5+/-48.3 vs. 65.4+/-5.6 g/m(2), P<0.01). From baseline
      to the third month of chronic HD, there were significant increases in EDV (78.6+/
      25.4 vs. 105.7+/-29.2 mL, P<0.01) and ESV (27.6+/-16.2 vs. 44.3+/-22.1 mL,
      P<0.01) and significant decreases in HBW (65.5 degrees +/-54.4 degrees  vs. 31.0
      degrees +/-15.7 degrees , P<0.01) and PSD (21.0 degrees +/-15.5 degrees  vs. 10.0
      degrees +/-8.2 degrees , P<0.01). CONCLUSION: Chronic HD decreased LV
      dyssynchrony and volume in patients with ESRD. Serial phase analysis of GSPECT
      images is a useful method of assessing the effects of long-term HD on LV
      dyssynchrony and volume in patients with ESRD.

PMID- 25959199
TI  - Beraprost Sodium Protects Against Diabetic Nephropathy in Patients with
      Arteriosclerosis Obliterans: A Prospective, Randomized, Open-label Study.
AB  - BACKGROUND: Inhibition of the renin-angiotensin system (RAS) has been used to
      treat diabetic nephropathy. However, RAS inhibition increases the risk of renal
      complications. In this study, we evaluated the effect of combining RAS inhibitor
      treatment with beraprost sodium (BPS), a prostaglandin I2 analog, in diabetic
      nephropathy with arteriosclerosis obliterans. METHODS: This study was a
      prospective, randomized, open-label study. Twenty-six Japanese patients (age >30
      years) with diabetic nephropathy and arteriosclerosis obliterans were randomly
      assigned to the BPS group (n=13), which received the combination of an RAS
      inhibitor and BPS (120 MUg/day) therapy, or the control group (n=13), which
      received only an RAS inhibitor. Patients were followed up for 1 year. The primary
      endpoint was the effect of BPS on renal function. RESULTS: In the control group,
      serum creatinine (1.64+/-0.87 to 2.34+/-1.53 mg/dL, p<0.001), 1/creatinine
      (0.82+/-0.47 to 0.65+/-0.47, p=0.003) cystatin C (1.77+/-0.61 to 2.18+/-0.86
      mg/L, p<0.001), and the estimated glomerular filtration rate (43.9+/-26.1 to
      34.0+/-24.6 mL/min/1.73 m(2), p=0.004) were significantly worsened 48 weeks after
      the start of treatment. Conversely, in the BPS group, serum creatinine (1.71+/
      0.75 to 1.66+/-0.81 mg/dL, p=0.850), 1/creatinine (0.66+/-0.19 to 0.71+/-0.25,
      p=0.577), cystatin C (1.79+/-0.55 to 1.80+/-0.57 mg/L, p=0.999), and the
      estimated glomerular filtration rate (35.8+/-10.8 to 38.7+/-14.4 mL/min/1.73
      m(2), p=0.613) were unchanged. CONCLUSIONS: Combination treatment with BPS and an
      RAS inhibitor prevented the progression of diabetic nephropathy. These
      observations should be confirmed in large-scale studies with long-term follow-up.

PMID- 25959200
TI  - Altered Microglia in the Amygdala Are Involved in Anxiety-related Behaviors of a
      Copy Number Variation Mouse Model of Autism.
AB  - BACKGROUND AND PURPOSE: Autism spectrum disorder (ASD) is a neurodevelopmental
      disorder with a strong genetic basis. Although anxiety is a common major
      psychiatric condition in ASD, the underlying mechanisms of the anxiety are poorly
      understood. In individuals with ASD, evidence indicates a structural abnormality
      in the amygdala, a key component involved in anxiety and social behavior.
      Microglia, which are central nervous system-resident immune cells implicated in
      neurodevelopmental processes, are also reportedly altered in ASD. In the present
      study, we examined the involvement of microglia in the anxiety-related behaviors
      of ASD model mouse. METHODS: Mice that have a 6.3-Mb paternal duplication
      (patDp/+) corresponding to human chromosome 15q11-q13 were used as an ASD model.
      Iba1, a microglial activation marker, was examined in the amygdala using
      immunofluorescence. Effects of perinatal treatment with minocycline, a microglial
      modulator, on anxiety-related behaviors were examined in neonatal and adolescent
      patDp/+ mice. RESULTS: In patDp/+ mice, Iba1 was decreased in the basolateral
      amygdala at postnatal day 7, but not at postnatal days 37-40. Perinatal treatment
      with minocycline restored the Iba1 expression and reduced anxiety-related
      behaviors in patDp/+ adolescent mice. CONCLUSIONS: Perinatal microglia in the
      basolateral amygdala may play a pathogenic role in the anxiety observed in a
      mouse model of ASD with duplication of human chromosome 15q11-q13.

PMID- 25959201
TI  - Incidence of nausea and vomiting induced by oxycodone administered with
      prochlorperazine in Japanese cancer patients.
AB  - BACKGROUND: Nausea and vomiting are the most frequent side effects of opioids and
      may cause the opioids to be discontinued. New methods for preventing opioid
      induced nausea can improve cancer pain management. Oxycodone is one of the most
      frequently used opioid used in Japan because patients receiving oxycodone report
      less nausea and vomiting than do patients receiving morphine. The reported
      incidence of oxycodone-induced nausea varies widely, although the true incidence
      remains unclear. As a first step toward preventing oxycodone-induced nausea, we
      aimed to determine the incidence of and risk factors for oxycodone-induced nausea
      and vomiting. METHODS: In this observational study, we analyzed a series of
      consecutive inpatients with cancer who received oxycodone with prochlorperazine
      as a preventive antiemetic agent. Oxycodone (5 mg) was administered either at
      08:00 and 20:00 or at 09:00 and 21:00, and prochlorperazine (5 mg) was also given
      at the same times for 5 days. RESULTS: Of the 145 enrolled patients, 138 were
      suitable for analysis. The incidence of nausea was 18.1%, and that of vomiting
      was 5.8%. The incidence of nausea was higher, but not to a significant degree, in
      women than in men (P=0.07). Furthermore, the incidence of vomiting in women was
      equal to that in men (P=0.28), whereas the incidences of both nausea (P=0.99) and
      vomiting (P=0.89) in elderly patients were equal to those in younger patients. In
      addition, the incidence of nausea (P=0.52) and vomiting (P=0.91) in patients with
      digestive system cancer was equal to that of patients with non-digestive system
      cancer. CONCLUSIONS: The incidence of nausea induced by oxycodone with
      prochlorperazine was 18.1% in opioid-naive Japanese inpatients. Female sex may be
      a risk factor for oxycodone-induced nausea. These results suggest that a clinical
      study would require 314 participants (157 in each group) to decrease the
      incidence from 18% to 8% (10% decrease) with a new preventive treatment (alpha
      error=0.05, beta error=0.2).

PMID- 25959202
TI  - Unilateral femoral fracture in a low birth weight infant: a case report.
AB  - Femoral fractures due to birth trauma are an extremely rare but important birth
      injury. While vaginal breech delivery, although rare, can cause femur fracture,
      abdominal breech delivery is not expected to cause fracture. Here we report on a
      low birth weight infant who was delivered by cesarean section for breech
      presentation at 30 1/7 weeks of gestation and sustained a unilateral fracture of
      the femoral shaft. 

PMID- 25959203
TI  - Stress fracture of the radial styloid process in a judo player: a case report.
AB  - Stress fractures of the upper limbs are uncommon, and are most often reported as
      individual cases or small series. In particularly, stress fractures around the
      wrist are even less common. A stress fracture of the radial styloid process in a
      judo player was surgically treated, and a favorable treatment outcome was
      obtained. A 16-year-old adolescent boy experienced pain in the right wrist, with
      no apparent trigger, while playing judo. Stress fracture of the radial styloid
      process was diagnosed with plain radiographs and was treated conservatively with
      cast immobilization. Although bone union was achieved, the fracture recurred
      after he resumed paying judo. Thus, surgical treatment was performed. The
      procedure was resection of the distal bone fragment. He resumed practicing 2
      months postoperatively and returned to judo matches after 1 more month. As of 1
      year after distal bone fragment resection, he was able to participate in judo
      without pain, limited range of motion, or instability of the wrist. 

PMID- 25959204
TI  - Spontaneous rupture of a simple hepatic cyst: report of a case.
AB  - We describe the spontaneous rupture of a simple hepatic cyst. A 62-year-old woman
      was admitted for right upper quadrant pain of sudden onset. The patient denied a
      history of abdominal trauma. Computed tomography of the abdomen showed a 13-cm
      diameter solitary hepatic cyst in the right lobe. Part of the cyst surface was
      irregular, and the internal echo was heterogeneous. Retained fluid was detected
      under the liver capsule. Ten days after admission, computed tomography revealed
      that the volume of fluid retained under the liver capsule had decreased but that
      the hepatic cyst had enlarged again. The patient was referred to our hospital for
      further evaluation and treatment. Physical examination revealed mild right upper
      quadrant pain, but no signs or symptoms of peritonitis or abnormalities of the
      chest or heart. Percutaneous puncture was performed with a needle and an 8-French
      pigtail catheter under ultrasonographic guidance. Brown serous fluid was
      aspirated. After the removal of approximately 1,000 mL of fluid, contrast medium
      was injected to check for communications between the cyst and the biliary tree
      and to document the absence of leakage into the peritoneal cavity. After complete
      aspiration of the cyst fluid, 200 mg of minocycline hydrochloride dissolved in 10
      mL of saline was injected into the cyst, and the catheter was flushed with 10 mL
      of saline (total volume of saline, 20 mL). The catheter was then clamped for 30
      minutes. After percutaneous aspiration, the patient's symptoms resolved.
      Minocycline hydrochloride was injected daily for 7 days, and the catheter was
      removed. There has been no evidence of recurrence after 2 years. 

PMID- 25959205
TI  - Seronegative Antiphospholipid Syndrome with Anti-phosphatidylethanolamine
      Antibody in a Boy.
AB  - Antiphospholipid syndrome (APS) is an autoimmune disease caused by
      antiphospholipid antibodies. At our institution, APS is diagnosed on the basis of
      the Sapporo criteria, which consist of thrombosis and recurrent pregnancy-related
      complications and the following laboratory findings: the presence of lupus
      anticoagulant, anticardiolipin antibody, or anti-beta2 glycoprotein 1 antibody.
      However, we sometimes treat patients we strongly suspect of having APS but who do
      not satisfy the laboratory criteria. To accommodate such suspected cases, a
      subtype of APS termed seronegative APS has been proposed. Here, we report on a
      man with chronic thromobocytopenic purpura since the age of 3 years and multiple
      cerebral infarctions since the age of 14 years who finally received a diagnosis
      of seronegative APS with positive antiphosphatidylethanolamine antibodies. 

PMID- 25959207
TI  - Stability of energy metabolites-An often overlooked issue in metabolomics
      studies: A review.
AB  - Recent advances in analytical chemistry have set the stage for metabolite
      profiling to help understand complex molecular processes in physiology. Despite
      ongoing efforts, there are concerns regarding metabolomics workflows, since it
      has been shown that internal (enzyme activity, blood contamination, and the
      dynamic nature of metabolite concentrations) as well as external factors
      (storage, handling, and analysis method) may affect the metabolome profile. Many
      metabolites are intrinsically instable, particularly some of those associated
      with central carbon metabolism. While enzymatic conversions have been studied in
      great detail, nonenzymatic, chemical conversions received comparatively little
      attention. This review aims to give an in-depth overview of nonenzymatic energy
      metabolite degradation/interconversion chemistry focusing on a selected range of
      metabolites. Special attention will be given to qualitative (degradation
      pathways) as well as quantitative aspects, that may affect the acquisition of
      accurate data in the context of metabolomics studies. Problems related to the use
      of isotopically labeled internal standards hindering the quantitative analysis of
      common metabolites will be presented with an experimental example. Finally,
      general conclusions and perspectives are given.

PMID- 25959206
TI  - Tie-mediated signal from apoptotic cells protects stem cells in Drosophila
      melanogaster.
AB  - Many types of normal and cancer stem cells are resistant to killing by
      genotoxins, but the mechanism for this resistance is poorly understood. Here we
      show that adult stem cells in Drosophila melanogaster germline and midgut are
      resistant to ionizing radiation (IR) or chemically induced apoptosis and dissect
      the mechanism for this protection. We find that upon IR the receptor tyrosine
      kinase Tie/Tie-2 is activated, leading to the upregulation of microRNA bantam
      that represses FOXO-mediated transcription of pro-apoptotic Smac/DIABLO
      orthologue, Hid in germline stem cells. Knockdown of the IR-induced putative Tie
      ligand, Pvf1, a functional homologue of human Angiopoietin, in differentiating
      daughter cells renders germline stem cells sensitive to IR, suggesting that the
      dying daughters send a survival signal to protect their stem cells for future
      repopulation of the tissue. If conserved in cancer stem cells, this mechanism may
      provide therapeutic options for the eradication of cancer. 

PMID- 25959208
TI  - Clinical usefulness of the definitions for defining characteristics of activity
      intolerance, excess fluid volume and decreased cardiac output in decompensated
      heart failure: a descriptive exploratory study.
AB  - AIMS AND OBJECTIVES: To assess the clinical usefulness of the operational
      definitions for the defining characteristics of the NANDA International nursing
      diagnoses, activity intolerance, decreased cardiac output and excess fluid
      volume, and the concomitant presence of those diagnoses in patients with
      decompensated heart failure. BACKGROUND: Content validity of the operational
      definitions for the defining characteristics of activity intolerance, excess
      fluid volume and decreased cardiac output have been previously validated by
      experts. Their clinical usefulness requires clinical validation. DESIGN: This was
      a descriptive exploratory study. METHODS: Two expert nurses independently
      assessed 25 patients with decompensated heart failure for the presence or absence
      of 29 defining characteristics. Interrater reliability was analysed using the
      Kappa coefficient as a measure of clinical usefulness. The Fisher's exact test
      was used to test the association of the defining characteristics of activity
      intolerance and excess fluid volume in the presence of decreased cardiac output,
      and the correlation between the three diagnoses. RESULTS: Assessments regarding
      the presence of all defining characteristics reached 100% agreement, except with
      anxiety. Five defining characteristics of excess fluid volume were significantly
      associated with the presence of decreased cardiac output. Concomitant presence of
      the three diagnoses occurred in 80% of the patients. However, there was no
      significant correlation between the three diagnoses. CONCLUSIONS: The operational
      definitions for the diagnoses had strong interrater reliability, therefore they
      were considered clinically useful. Only five defining characteristics were
      representative of the association between excess fluid volume and decreased
      cardiac output. Therefore, excess fluid volume is related to decreased cardiac
      output, although these diagnoses are not necessarily associated with activity
      intolerance. RELEVANCE TO CLINICAL PRACTICE: The operational definitions may
      favour early recognition of the sequence of responses to decompensation, guiding
      the choice of common interventions to improve or resolve excess fluid volume and
      decreased cardiac output.

PMID- 25959209
TI  - Vitamin B12 and folate levels increase during treatment of iron deficiency
      anaemia in young adult woman.
AB  - INTRODUCTION: The relationship between iron deficiency and vitamin B12 and folate
      was recognized several decades ago. Combined deficiency is important in clinical
      practice owing to its relationship with malabsorption syndromes. By contrast,
      iron deficiency and low levels of serum vitamin B12 with normal metabolic markers
      were often found mostly in young adults. In this work, vitamin B12/folate changes
      were investigated during treatment of iron deficiency anaemia (IDA) with
      pharmacological iron in young adult women. METHODS: A cohort of 35 young adult
      women with IDA was treated with oral iron. An haematological response was
      obtained in 97.2% at 4-month follow-up. Changes in serum vitamin B12, serum
      folate and other biochemical parameters were monitored. RESULTS: Treatment with
      iron increased significantly serum folate and vitamin B12 from baseline. This
      increase was also observed in vitamin B12 levels <=200 pmol/L (six patients,
      17.1%), in whom serum vitamin B12 was above 200 pmol/L at the end of the study in
      all cases. Other biochemical parameters also changed. Significant increases were
      seen for glucose (P = 0.012), uric acid (P < 0.001), total cholesterol (P =
      0.023), HDL cholesterol (P = 0.026) and bilirubin (P < 0.001). Urea decreased
      significantly (P = 0.036). CONCLUSIONS: Data from our work suggest that iron
      deficiency could affect many metabolic pathways, including vitamin B12, folate
      and lipids. These changes normalize after iron therapy, even in women with
      baseline low levels of serum vitamin B12. Healthcare practitioners should be
      aware of these changes in IDA management. The mechanisms controlling these
      changes remain to be explained, but they are probably related to the control of
      iron homeostasis (iron deficiency mediated stimuli).

PMID- 25959210
TI  - Bleomycin in the setting of lung fibrosis induction: From biological mechanisms
      to counteractions.
AB  - Bleomycin (BLM) is a drug used to treat different types of neoplasms. BLM's most
      severe adverse effect is lung toxicity, which induces remodeling of lung
      architecture and loss of pulmonary function, rapidly leading to death. While its
      clinical role as an anticancer agent is limited, its use in experimental settings
      is widespread since BLM is one of the most widely used drugs for inducing lung
      fibrosis in animals, due to its ability to provoke a histologic lung pattern
      similar to that described in patients undergoing chemotherapy. This pattern is
      characterized by patchy parenchymal inflammation, epithelial cell injury with
      reactive hyperplasia, epithelial-mesenchymal transition, activation and
      differentiation of fibroblasts to myofibroblasts, basement membrane and alveolar
      epithelium injuries. Several studies have demonstrated that BLM damage is
      mediated by DNA strand scission producing single- or double-strand breaks that
      lead to increased production of free radicals. Up to now, the mechanisms involved
      in the development of pulmonary fibrosis have not been fully understood; several
      studies have analyzed various potential biological molecular factors, such as
      transforming growth factor beta 1, tumor necrosis factor alpha, components of the
      extracellular matrix, chaperones, interleukins and chemokines. The aim of this
      paper is to review the specific characteristics of BLM-induced lung fibrosis in
      different animal models and to summarize modalities and timing of in vivo drug
      administration. Understanding the mechanisms of BLM-induced lung fibrosis and of
      commonly used therapies for counteracting fibrosis provides an opportunity for
      translating potential molecular targets from animal models to the clinical arena.

PMID- 25959211
TI  - Type 1 diabetes and T regulatory cells.
AB  - T-regulatory cells (Tregs) play a fundamental role in the creation and
      maintenance of peripheral tolerance. Deficits in the numbers and/or function of
      Tregs may be an underlying cause of human autoimmune diseases including type 1
      Diabetes Mellitus (T1D), whereas an over-abundance of Tregs can hinder immunity
      against cancer or pathogens. The importance of Tregs in the control of
      autoimmunity is well established in a variety of experimental animal models. In
      mice, manipulating the numbers and/or function of Tregs can decrease pathology in
      a wide range of contexts, including autoimmunity and it is widely assumed that
      similar approaches will be possible in humans. T1D, the most prevalent human
      autoimmune disease, has been a focus of interventions either through direct and
      indirect in vivo proliferations or through adoptive transfer of the in vitro
      generated antigen specific and non specific Treg. Some challenges still need to
      be addressed, including a more specific phenotype marker for Tregs; the
      reproducibility of satisfactory animal results in human and the reconcile of
      discrepancies between in vitro and in vivo studies. In this article, we will
      highlight the role of Tregs in autoimmune disease in general with a special focus
      on T1D, highlighting progress made and challenges ahead in developing Treg-based
      therapies. 

PMID- 25959212
TI  - Performance of serum galactomannan in patients with allergic bronchopulmonary
      aspergillosis.
AB  - Few studies have evaluated the performance of serum galactomannan (GM) in
      patients with allergic bronchopulmonary aspergillosis (ABPA). Herein, we analyse
      the diagnostic performance of serum GM in ABPA. Consecutive subjects with ABPA
      and asthma underwent GM estimation using the Platelia assay (Bio-Rad
      Laboratories). An optical density index of >0.5 was considered positive. One
      hundred and twenty subjects (70 ABPA, 50 asthma) with a mean (SD) age of 33.0
      (13.1) were included in the study. The serum GM antigen was positive in 18
      (25.7%) subjects with ABPA compared to 9 (18%) subjects with asthma without ABPA
      (P = 0.32). The sensitivity of the serum GM antigen test in patients with ABPA
      was 25.7% [95% confidence intervals (CI), 16-38] while the specificity was 82%
      (95% CI, 69-91). The positive and negative predictive values were 66.7% (95% CI,
      46-84%) and 44.1% (95% CI, 34-55), respectively. The area under the ROC curve was
      0.54 (95% CI, 0.44-0.64). The sensitivity increased and the specificity decreased
      with decreasing the serum GM cutoff, and vice versa. The results of this study
      suggest that serum GM estimation has a limited role in the diagnostic workup of
      patients with ABPA.

PMID- 25959214
TI  - Splitting versus lumping: reconsidering the definition of transfusion-related
      acute lung injury.

PMID- 25959215
TI  - Transfusion-related acute lung injury: three decades of progress but miles to go
      before we sleep.

PMID- 25959213
TI  - Differential contributions of hippocampus and medial prefrontal cortex to self
      projection and self-referential processing.
AB  - Converging evidence points to a neural network that supports a range of abilities
      including remembering the past, thinking about the future, and introspecting
      about oneself and others. Neuroimaging studies find hippocampal activation during
      event construction tasks, and patients with hippocampal amnesia are impaired in
      their ability to (re)construct events of the past and the future. Neuroimaging
      studies of constructed experiences similarly implicate the medial prefrontal
      cortex (mPFC), but it remains unknown whether the mPFC is critical for such
      processes. The current study compares performance of five patients with bilateral
      mPFC damage, six patients with bilateral hippocampal damage, and demographically
      matched comparison participants on an event construction task. Participants were
      given a neutral cue word and asked to (re)construct events across four time
      conditions: real past, imagined past, imagined present, and future. These event
      narratives were analyzed for the number of internal and external details to
      quantify the extent of episodic (re)experiencing. Given the literature on the
      involvement of the mPFC in self-referential processing, we also analyzed the
      event narratives for self-references. The patients with mPFC damage did not
      differ from healthy comparison participants in their ability to construct highly
      detailed episodic events across time periods but displayed disruptions in their
      incorporation of the self. Patients with hippocampal damage showed the opposite
      pattern; they were impaired in their ability to construct highly detailed
      episodic events across time periods but not in their incorporation of the self.
      The results suggest differential contributions of hippocampus and medial
      prefrontal cortex to the distributed neural network for various forms of self
      projection. 

PMID- 25959216
TI  - The growing role of AABB clinical practice guidelines in improving patient care.

PMID- 25959217
TI  - Propofol as a cause of lipemic plasma.

PMID- 25959219
TI  - Maintenance of the in vitro storage properties of apheresis platelets suspended
      in PAS-F after a 24-hour interruption of agitation.

PMID- 25959220
TI  - Structural effects of multiple pathogenic mutations suggest a model for the
      initiation of misfolding of the prion protein.
AB  - A molecular understanding of the prion diseases requires delineation of the
      origin of misfolding of the prion protein (PrP). An understanding of how
      different disease-linked mutations affect the structure and dynamics of native
      monomeric PrP can provide a clue about how misfolding commences. In this study,
      hydrogen-deuterium exchange mass spectrometry was used to show that several
      disease-linked mutant variants, which are thermodynamically destabilized, share a
      common structural perturbation in their native states: helix 1 is destabilized to
      an extent that correlates well with the destabilization of the native protein.
      The mutant variants misfold and form oligomers faster than does the wild-type
      protein, at rates that increase exponentially with the extent to which helix 1 is
      destabilized in the native protein. It appears, therefore, that the loss of helix
      1 structure marks the beginning of PrP misfolding and oligomerization. 

PMID- 25959221
TI  - A correlation between thermodynamic properties, thermal expansion and electrical
      resistivity of Ag-28% Cu nanopowders processed by the mechanical alloying route.
AB  - Thermodynamic properties, thermal expansion and electrical resistivity of the Ag
      28% Cu nanopowders processed by the mechanical alloying route have been
      investigated in the temperature range from ambient to 1048 K. The thermodynamic
      properties represented by the relative enthalpy, the specific heat capacity, the
      relative entropy and the Gibbs energy function obtained from drop calorimetric
      measurements have been used to reveal the occurrence of the micro-relaxation
      process, as well as of the correlative effects of decomposition and growth
      processes. On the basis of the results, the parameters that favour stable
      nanostructured systems in Ag-28% Cu powders synthesized by the mechanical
      alloying route have been identified. The correlation of the energetic parameters
      with thermal expansion and electrical resistivity in mechanical alloyed
      nanocrystalline powders with the eutectic composition is discussed. 

PMID- 25959222
TI  - Synthetic anion transporters that bear a terminal ethynyl group.
AB  - Cl(-) transporters that bear a terminal ethynyl group were synthesized; they
      consist of non-pyrrolic hydrogen bond motifs such as phenolic OH, amide NH, and
      triazole CH. The ethynyl group of these non-pyrrolic analogs plays an important
      role in chloride efflux and they exhibit no significant cytotoxic activity. 

PMID- 25959223
TI  - Biochar helps enhance maize productivity and reduce greenhouse gas emissions
      under balanced fertilization in a rainfed low fertility inceptisol.
AB  - Maize production plays an important role in global food security, especially in
      arid and poor-soil regions. Its production is also increasing in China in terms
      of both planting area and yield. However, maize productivity in rainfed croplands
      is constrained by low soil fertility and moisture insufficiency. To increase the
      maize yield, local farmers use NPK fertilizer. However, the fertilization regime
      (CF) they practice is unbalanced with too much nitrogen in proportion to both
      phosphorus and potassium, which has led to low fertilizer use efficiency and
      excessive greenhouse gases emissions. A two-year field experiment was conducted
      to assess whether a high yielding but low greenhouse gases emission system could
      be developed by the combination of balanced fertilization (BF) and biochar
      amendment in a rainfed farmland located in the Northern region of China. Biochar
      was applied at rates of 0, 20, and 40 t/ha. Results show that BF and biochar
      increased maize yield and partial nutrient productivity and decreased nitrous
      oxide (N2O) emission. Under BF the maize yield was 23.7% greater than under CF.
      N2O emissions under BF were less than half that under CF due to a reduced N
      fertilizer application rate. Biochar amendment decreased N2O by more than 31%
      under CF, while it had no effect on N2O emissions under BF. Thus BF was effective
      at maintaining a high maize yield and reducing greenhouse gases emissions. If
      combined with biochar amendment, BF would be a good way of sustaining low carbon
      agriculture in rainfed areas.

PMID- 25959224
TI  - Biochar-induced concomitant decrease in ammonia volatilization and increase in
      nitrogen use efficiency by wheat.
AB  - Ammonia (NH3) volatilization is a major nitrogen (N) loss from the soil,
      especially under tropical conditions, NH3 volatilization results in low N use
      efficiency by crops. Incubation experiments were conducted using five soils (pH
      5.5-9.0), three N sources such as, urea, di-ammonium phosphate (DAP), and poultry
      manure (PM) and two biochars such as, poultry litter biochar (PL-BC) and
      macadamia nut shell biochar (MS-BC). Ammonia volatilization was higher at soil
      with higher pH (pH exceeding 8) due to the increased hydroxyl ions. Among the N
      sources, urea recorded the highest NH3 volatilization (151.6 mg kg(-1)soil)
      followed by PM (124.2 mg kg(-1)soil) and DAP (99 mg kg(-1)soil). Ammonia
      volatilization was reduced by approximately 70% with PL-BC and MS-BC. The
      decreased NH3 volatilization with biochars is attributed to multiple mechanisms
      such as NH3 adsorption/immobilization, and nitrification. Moreover, biochar
      increased wheat dry weight and N uptake as high as by 24.24% and 76.11%,
      respectively. This study unravels the immense potential of biochar in decreasing
      N volatilization from soils and simultaneously improving use efficiency by wheat.

PMID- 25959225
TI  - Active hematopoietic hubs in Drosophila adults generate hemocytes and contribute
      to immune response.
AB  - Blood cell development in Drosophila shares significant similarities with
      vertebrate. The conservation ranges from biphasic mode of hematopoiesis to
      signaling molecules crucial for progenitor cell formation, maintenance, and
      differentiation. Primitive hematopoiesis in Drosophila ensues in embryonic head
      mesoderm, whereas definitive hematopoiesis happens in larval hematopoietic organ,
      the lymph gland. This organ, with the onset of pupation, ruptures to release
      hemocytes into circulation. It is believed that the adult lacks a hematopoietic
      organ and survives on the contribution of both embryonic and larval
      hematopoiesis. However, our studies revealed a surge of blood cell development in
      the dorsal abdominal hemocyte clusters of adult fly. These active hematopoietic
      hubs are capable of blood cell specification and can respond to bacterial
      challenges. The presence of progenitors and differentiated hemocytes embedded in
      a functional network of Laminin A and Pericardin within this hematopoietic hub
      projects it as a simple version of the vertebrate bone marrow. 

PMID- 25959227
TI  - Determination of pyruvic acid concentration using a bioluminescence system from
      Photobacterium leiognathi.
AB  - A novel, highly sensitive and selective bacterial luminescence method for the
      detection of pyruvic acid (PA) is reported here. This method is based on a
      reaction system catalyzed by lactate dehydrogenase (LDH) with the bacterial
      luciferase-FMN:NADH oxidoreductase bioluminescence system in vitro. The reduced
      nicotinamide adenine dinucleotide (NADH) involved in the LDH reaction system
      could be quantitatively analyzed by the bioluminescence system. A good linear
      relationship between the luminescence intensity and pyruvic acid concentration
      was exhibited within the range of 0.00014-0.001 mol l(-1), and the pyruvic acid
      detection limit was found to be 8.537 * 10(-5) mol l(-1). This method was
      successfully applied to the detection of PA in quail serum with a good recovery
      of over 70%. 

PMID- 25959226
TI  - Mechanistic insights into the anchorage of the contractile ring by anillin and
      Mid1.
AB  - Anillins and Mid1 are scaffold proteins that play key roles in anchorage of the
      contractile ring at the cell equator during cytokinesis in animals and fungi,
      respectively. Here, we report crystal structures and functional analysis of human
      anillin and S. pombe Mid1. The combined data show anillin contains a cryptic C2
      domain and a Rho-binding domain. Together with the tethering PH domain, three
      membrane-associating elements synergistically bind to RhoA and phospholipids to
      anchor anillin at the cleavage furrow. Surprisingly, Mid1 also binds to the
      membrane through a cryptic C2 domain. Dimerization of Mid1 leads to high affinity
      and preference for PI(4,5)P2, which stably anchors Mid1 at the division plane,
      bypassing the requirement for Rho GTPase. These findings uncover the unexpected
      general machinery and the divergent regulatory logics for the anchorage of the
      contractile ring through the anillin/Mid1 family proteins from yeast to humans. 

PMID- 25959228
TI  - The Role of Semantic Clustering in Optimal Memory Foraging.
AB  - Recent studies of semantic memory have investigated two theories of optimal
      search adopted from the animal foraging literature: Levy flights and marginal
      value theorem. Each theory makes different simplifying assumptions and addresses
      different findings in search behaviors. In this study, an experiment is conducted
      to test whether clustering in semantic memory may play a role in evidence for
      both theories. Labeled magnets and a whiteboard were used to elicit spatial
      representations of semantic knowledge about animals. Category recall sequences
      from a separate experiment were used to trace search paths over the spatial
      representations of animal knowledge. Results showed that spatial distances
      between animal names arranged on the whiteboard were correlated with inter
      response intervals (IRIs) during category recall, and distributions of both
      dependent measures approximated inverse power laws associated with Levy flights.
      In addition, IRIs were relatively shorter when paths first entered animal
      clusters, and longer when they exited clusters, which is consistent with marginal
      value theorem. In conclusion, area-restricted searches over clustered semantic
      spaces may account for two different patterns of results interpreted as
      supporting two different theories of optimal memory foraging. 

PMID- 25959229
TI  - Multiphoton luminescence imaging of chemically functionalized multi-walled carbon
      nanotubes in cells and solid tumors.
AB  - The intrinsic nonlinear photoluminescence (PL) property of chemically
      functionalized multi-walled nanotubes MWNTs (f-MWNTs) is reported in this study.
      f-MWNTs are imaged in fixed lung epithelial cancer cells (A549) and Kupffer cells
      in vitro, and in subcutaneously implanted solid tumors in vivo, for the first
      time, using multiphoton PL and fluorescence lifetime imaging (FLIM). Multiphoton
      imaging in the near-infrared excitation region (~750-950 nm), employed in this
      study in a label-free manner, provides sensitivity and resolution optimal to
      track f-MWNTs within intra-cellular compartments and facilitates tumour imaging
      and sentinel lymph node tracking in vivo. Wider applications include employing
      this technique in live imaging of f-MWNTs in biological milieu to facilitate
      image-guided drug delivery. 

PMID- 25959231
TI  - Proteomics methods for discovering viral-host interactions.
AB  - The functions of many viral proteins involve direct interactions with specific
      host proteins. Therefore considerable insight into the functions of a viral
      protein and its mechanisms of action can come from applying proteomics approaches
      to viral proteins in order to identify their cellular binding partners. In this
      chapter we describe proteomics approaches that have proven to be the most useful
      in identifying host interactions of viral proteins in human cells. Caveats and
      potential alternatives for each step are also discussed. 

PMID- 25959230
TI  - Lamellar versus Micellar Structures-Aggregation Behavior of a Three-Chain
      Cationic Lipid Designed for Nonviral Polynucleotide Transfer.
AB  - The aggregation behavior of a cationic lipid, N-[6-amino-1-oxo-1-(N
      tetradecylamino)hexan-(2S)-2-yl]-N'-{2-[N,N-bis(2-aminoethyl)amino]ethyl}-2,2
      ditetradecylpropandiamide (DiTT4), is investigated in aqueous dispersions at
      different pH values (5, 7.3, and 10). An unusual aggregation behavior is observed
      whereby DiTT4 forms bilayer structures at pH 10 and 7.3. At pH 5, rod-like
      micelles are the dominant aggregate form. The thermotropic and lyotropic behavior
      is studied using differential scanning calorimetry, small-angle X-ray scattering,
      and FTIR spectroscopy. In addition, investigations at the air-water interface are
      performed by recording area-pressure-isotherms and infrared reflection-absorption
      (IRRA) spectra. Complementary dynamic light scattering experiments and
      transmission electron microscopy (TEM and cryoTEM) are also used. The ability of
      DiTT4 to complex plasmid DNA is investigated using fluorescence techniques and
      zeta potential measurements. Cell culture experiments demonstrate the ability of
      DiTT4 to enhance plasmid transfer in A549 cells. 

PMID- 25959232
TI  - Properties of transition metal substituted zinc sulfide hexamers and dodecamers.
AB  - Density functional theory was used to study the structural and electronic
      properties of endohedrally- and substitutionally-doped Zn6S6 and Zn12S12 clusters
      with first-row transition metal atoms. Generally, the lowest energy electronic
      state of the cluster is that with the maximum multiplicity (Ti and Cr are
      exceptions). Substitutionally-doped clusters have greater binding energies (per
      atom) for both cluster sizes, providing an indication that similar doping will be
      preferred in the bulk material as well. The results are relevant to thin films of
      doped ZnS in which cluster formation is likely. 

PMID- 25959233
TI  - Quantitative proteomic analysis of cabernet sauvignon grape cells exposed to
      thermal stresses reveals alterations in sugar and phenylpropanoid metabolism.
AB  - Grapes (Vitis vinifera) are a valuable fruit crop and wine production is a major
      industry. Global warming and expanded range of cultivation will expose grapes to
      more temperature stresses in future. Our study investigated protein level
      responses to abiotic stresses, with particular reference to proteomic changes
      induced by the impact of four different temperature stress regimes, including
      both hot and cold temperatures, on cultured grape cells. Cabernet Sauvignon cell
      suspension cultures grown at 26 degrees C were subjected to 14 h of exposure to
      34 and 42 degrees C for heat stress, and 18 and 10 degrees C for cold stress.
      Cells from the five temperatures were harvested in biological triplicates and
      label-free quantitative shotgun proteomic analysis was performed. A total of 2042
      non-redundant proteins were identified from the five temperature points. Fifty
      five proteins were only detected in extreme heat stress conditions (42 degrees C)
      and 53 proteins were only detected at extreme cold stress conditions (10 degrees
      C). Gene Ontology (GO) annotations of differentially expressed proteins provided
      insights into the metabolic pathways that are involved in temperature stress in
      grape cells. Sugar metabolism displayed switching between alternative and
      classical pathways during temperature stresses. Additionally, nine proteins
      involved in the phenylpropanoid pathway were greatly increased in abundance at
      extreme cold stress, and were thus found to be cold-responsive proteins. All MS
      data have been deposited in the ProteomeXchange with identifier PXD000977
      (http://proteomecentral.proteomexchange.org/dataset/PXD000977). 

PMID- 25959234
TI  - Liver and spleen elastography using supersonic shear imaging for the non-invasive
      diagnosis of cirrhosis severity and oesophageal varices.
AB  - BACKGROUND: Elastography is a promising non-invasive approach for assessing liver
      fibrosis. We assessed diagnostic performances of liver and spleen stiffness using
      supersonic shear imaging for diagnosing cirrhosis severity and oesophageal
      varices. METHODS: 401 consecutive cirrhotic patients were prospectively enrolled
      from November 2012 to March 2014. All patients underwent liver and spleen
      stiffness measurement with supersonic shear imaging and Fibroscan. RESULTS:
      Failures of measurement were 6.2% and 29.2% for liver and spleen stiffness
      (supersonic shear imaging), and 18.4% for liver stiffness (Fibroscan). Liver and
      spleen stiffness were correlated with severity of cirrhosis, with values
      increasing according to Child-Pugh subclasses and presence of complications. With
      a negative predictive value >=90%, liver stiffness cut-offs for high-risk
      oesophageal varices, history of ascites, Child-Pugh B/C, variceal bleeding and
      clinical decompensation were 12.8, 19, 21.4, 30.5, and 39.4 kPa, respectively.
      Areas under the curve of spleen and liver stiffness (supersonic shear imaging),
      and liver stiffness (Fibroscan) were 0.80, 0.77 and 0.73 respectively for
      detection of oesophageal varices. CONCLUSION: Liver stiffness using supersonic
      shear imaging is a relevant diagnostic tool for assessing cirrhosis severity and
      its complications. Spleen stiffness shows promising results for the detection of
      oesophageal varices but is not yet sufficiently robust for clinical practice
      owing to high failure rates.

PMID- 25959235
TI  - Laser assisted removal of an embedded foreign body in the colon.

PMID- 25959236
TI  - Predictors of adherence to treatment in bronchiectasis.
AB  - OBJECTIVES: We aimed to determine if beliefs about treatment, clinical factors
      and quality of life predicted adherence to treatment in patients with
      bronchiectasis. METHODS: We recruited participants with confirmed bronchiectasis
      to a one-year study. We calculated adherence to treatment using medication
      possession ratios and self-report. Baseline Beliefs about Medicines, clinical,
      demographic and Quality of Life Questionnaire-Bronchiectasis data were collected.
      We used logistic regression to determine predictors of adherence to treatment
      during the subsequent year. RESULTS: Seventy-five participants were recruited.
      Beliefs about harm, age and total number of prescribed medications were
      predictors of adherence to inhaled antibiotics. Concerns about medication, age
      and Quality of Life Questionnaire-Bronchiectasis Treatment Burden were predictors
      of adherence to other respiratory medicines. Beliefs about necessity of airway
      clearance and age were predictors of adherence to airway clearance. CONCLUSION:
      Beliefs about treatment, age, number of prescribed medications and perceived
      treatment burden predicted subsequent adherence in bronchiectasis, thereby,
      providing potential targets for future interventions in this population.
      Clinicians can use these data to identify patients with bronchiectasis who might
      be at risk of non-adherence i.e. those who are younger, have concerns about
      medications, who do not think airway clearance is necessary or who are prescribed
      numerous medications.

PMID- 25959237
TI  - Workshop for new leaders: innovative midwifery teaching for obstetrics and
      gynecology residents.
AB  - The Workshop for New Leaders represents an innovative project undertaken by the
      midwifery faculty at a teaching hospital in New England. The midwifery faculty
      sought to expand their educational offerings to the obstetrics and gynecology
      residents. Utilizing creative thinking strategies, the idea for a leadership
      workshop was originated in an effort to augment the professionalism curriculum
      mandated by the Accreditation Council of Graduate Medical Education for
      residents. Over time, this workshop has become a highlight for each class. Not
      only has this workshop facilitated transition from learner to leader as the
      residents approach their final year of training, it has also helped to enhance
      interprofessional relationships. This article is part of a special series of
      articles that address midwifery innovations in clinical practice, education,
      interprofessional collaboration, health policy, and global health. 

PMID- 25959238
TI  - MED GATA factors promote robust development of the C. elegans endoderm.
AB  - The MED-1,2 GATA factors contribute to specification of E, the progenitor of the
      Caenorhabditis elegans endoderm, through the genes end-1 and end-3, and in
      parallel with the maternal factors SKN-1, POP-1 and PAL-1. END-1,3 activate elt-2
      and elt-7 to initiate a program of intestinal development, which is maintained by
      positive autoregulation. Here, we advance the understanding of MED-1,2 in E
      specification. We find that expression of end-1 and end-3 is greatly reduced in
      med-1,2(-) embryos. We generated strains in which MED sites have been mutated in
      end-1 and end-3. Without MED input, gut specification relies primarily on POP-1
      and PAL-1. 25% of embryos fail to make intestine, while those that do display
      abnormal numbers of gut cells due to a delayed and stochastic acquisition of
      intestine fate. Surviving adults exhibit phenotypes consistent with a primary
      defect in the intestine. Our results establish that MED-1,2 provide robustness to
      endoderm specification through end-1 and end-3, and reveal that gut
      differentiation may be more directly linked to specification than previously
      appreciated. The results argue against an "all-or-none" description of cell
      specification, and suggest that activation of tissue-specific master regulators,
      even when expression of these is maintained by positive autoregulation, does not
      guarantee proper function of differentiated cells. 

PMID- 25959239
TI  - Acetylations of Ftz-F1 and histone H4K5 are required for the fine-tuning of
      ecdysone biosynthesis during Drosophila metamorphosis.
AB  - The molting during Drosophila development is tightly regulated by the ecdysone
      hormone. Several steps of the ecdysone biosynthesis have been already identified
      but the regulation of the entire process has not been clarified yet. We have
      previously reported that dATAC histone acetyltransferase complex is necessary for
      the steroid hormone biosynthesis process. To reveal possible mechanisms
      controlled by dATAC we made assumptions that either dATAC may influence directly
      the transcription of Halloween genes involved in steroid hormone biosynthesis or
      it may exert an indirect effect on it by acetylating the Ftz-F1 transcription
      factor which regulates the transcription of steroid converting genes. Here we
      show that the lack of dATAC complex results in increased mRNA level and decreased
      protein level of Ftz-F1. In this context, decreased mRNA and increased protein
      levels of Ftz-F1 were detected upon treatment of Drosophila S2 cells with histone
      deacetylase inhibitor trichostatin A. We showed that Ftz-F1, the transcriptional
      activator of Halloween genes, is acetylated in S2 cells. In addition, we found
      that ecdysone biosynthetic Halloween genes are transcribed in S2 cells and their
      expression can be influenced by deacetylase inhibitors. Furthermore, we could
      detect H4K5 acetylation at the regulatory regions of disembodied and shade
      Halloween genes, while H3K9 acetylation is absent on these genes. Based on our
      findings we conclude that the dATAC HAT complex might play a dual regulatory role
      in Drosophila steroid hormone biosynthesis through the acetylation of Ftz-F1
      protein and the regulation of the H4K5 acetylation at the promoters of Halloween
      genes. 

PMID- 25959241
TI  - Heterojunction Solar Cells Based on Silicon and Composite Films of Graphene Oxide
      and Carbon Nanotubes.
AB  - Graphene oxide (GO) sheets have been used as the surfactant to disperse single
      walled carbon nanotubes (CNT) in water to prepare GO/CNT electrodes that are
      applied to silicon to form a heterojunction that can be used in solar cells.
      GO/CNT films with different ratios of the two components and with various
      thicknesses have been used as semitransparent electrodes, and the influence of
      both factors on the performance of the solar cell has been studied. The
      degradation rate of the GO/CNT-silicon devices under ambient conditions has also
      been explored. The influence of the film thickness on the device performance is
      related to the interplay of two competing factors, namely, sheet resistance and
      transmittance. CNTs help to improve the conductivity of the GO/CNT film, and GO
      is able to protect the silicon from oxidation in the atmosphere.

PMID- 25959240
TI  - Leukotriene B4-leukotriene B4 receptor axis promotes oxazolone-induced contact
      dermatitis by directing skin homing of neutrophils and CD8+ T cells.
AB  - Leukotriene B4 (LTB4 ) is a lipid mediator that is rapidly generated in
      inflammatory sites, and its functional receptor, BLT1, is mostly expressed on
      immune cells. Contact dermatitis is a common inflammatory skin disease
      characterized by skin oedema and abundant inflammatory infiltrates, primarily
      including neutrophils and CD8(+) T cells. The role of the LTB4 -BLT1 axis in
      contact dermatitis remains largely unknown. In this study, we found up-regulated
      gene expression of 5-lipoxygenase and leukotriene A4 hydrolase, two critical
      enzymes for LTB4 synthesis, BLT1 and elevated LTB4 levels in skin lesions of
      oxazolone (OXA)-induced contact dermatitis. BLT1 deficiency or blockade of LTB4
      and BLT1 by the antagonists, bestatin and U-75302, respectively, in the
      elicitation phase caused significant decreases in ear swelling and skin
      infiltrating neutrophils and CD8(+) T cells, which was accompanied by
      significantly reduced skin expression of CXCL1, CXCL2, interferon-gamma and
      interleukin-1beta. Furthermore, neutrophil depletion during the elicitation phase
      of OXA-induced contact dermatitis also caused significant decreases in ear
      swelling and CD8(+) T-cell infiltration accompanied by significantly decreased
      LTB4 synthesis and gene expression of CXCL2, interferon-gamma and interleukin
      1beta. Importantly, subcutaneous injection of exogenous LTB4 restored the skin
      infiltration of CD8(+) T cells in neutrophil-depleted mice following OXA
      challenge. Collectively, our results demonstrate that the LTB4 -BLT1 axis
      contributes to OXA-induced contact dermatitis by mediating skin recruitment of
      neutrophils, which are a major source of LTB4 that sequentially direct CD8(+) T
      cell homing to OXA-challenged skin. Hence, LTB4 and BLT1 could be potential
      therapeutic targets for the treatment of contact dermatitis. 

PMID- 25959242
TI  - Interactional synchrony in chimpanzees: Examination through a finger-tapping
      experiment.
AB  - Humans often unconsciously coordinate behaviour with that of others in daily
      life. This interpersonal coordination, including mimicry and interactional
      synchrony, has been suggested to play a fundamental role in social interaction.
      If this coordinative behavior is socially adaptive, it may be shared with other
      highly social animal species. The current study targeted chimpanzees, which
      phylogenetically are the closest living relatives of humans and live in complex
      social groups, and examined whether interactional synchrony would emerge in pairs
      of chimpanzees when auditory information about a partner's movement was provided.
      A finger-tapping task was introduced via touch panels to elicit repetitive and
      rhythmic movement from each chimpanzee. We found that one of four chimpanzees
      produced significant changes in both tapping tempo and timing of the tapping
      relative to its partner's tap when auditory sounds were provided. Although the
      current results may have limitations in generalizing to chimpanzees as a species,
      we suggest that a finger-tapping task is one potential method to investigate
      interactional synchrony in chimpanzees under a laboratory setup. 

PMID- 25959243
TI  - Adipose tissue-derived mesenchymal stem cells as a strategy to improve recovery
      after stroke.
AB  - INTRODUCTION: Based on the positive results observed in experimental animal
      models, adipose tissue-derived mesenchymal stem cells (AD-MSCs) constitute a
      promising therapy for stroke treatment. However, several aspects need to be
      clarified to identify the optimal conditions for successful clinical translation.
      AREAS COVERED: This review focuses on AD-MSC treatment for ischemic and
      hemorrhagic stroke in experimental animal models. In addition, we will explore
      the optimization of treatment conditions including AD-MSC production,
      administration routes and therapeutic windows for their appropriate use in
      patients. Finally we will provide an update on clinical trials on this therapy.
      EXPERT OPINION: Compared with other cell types, AD-MSCs have been less
      investigated in stroke studies. Currently, experimental animal models have shown
      safety and efficacy with this treatment after stroke. Due to several advantages
      of AD-MSCs, such as their abundance and accessibility, they can be considered a
      promising strategy for use in patients. However, many questions are still to be
      resolved regarding their mechanisms of action, immune system modulation and the
      effects of AD-MSCs on all components of the brain that may be affected after
      ischemic and hemorrhagic strokes.

PMID- 25959244
TI  - Pancreatic acinar cell carcinoma with bilateral ovarian metastases, panniculitis
      and polyarthritis treated with FOLFIRINOX chemotherapy regimen. A case report and
      review of the literature.
AB  - Pancreatic acinar cell carcinoma (PACC) is a rare pancreatic tumor, with an
      estimated frequency of less than 1% of pancreatic malignancies. There are no
      prospective studies to guide diagnostic or therapeutic algorithms. We report the
      case of a 36 year-old woman, diagnosed of a pancreatic tumor with liver and
      peritoneal metastases that was initially managed as a neuroendocrine tumor with
      temozolomide and capecitabine. After two cycles a severely painful arthritis
      developed in her left ankle with panniculitis and extensive fat necrosis, and CT
      scan demonstrated progressive disease. Pathology of the primary was reassessed
      establishing the diagnosis of PACC. The patient started treatment with FOLFIRINOX
      regimen, achieving clinical benefit and disease stabilization. We also briefly
      reviewed the literature on this rare subtype of pancreatic tumor. 

PMID- 25959245
TI  - A histomorphologic comparison of familial and sporadic pancreatic cancers.
AB  - BACKGROUND: It is estimated that approximately 10% of pancreatic cancers have a
      familial component. Many inheritable genetic syndromes are associated with
      increased risk of pancreatic cancer, such as Peutz-Jeghers syndrome, hereditary
      breast-ovarian cancer and familial atypical multiple mole melanoma, but these
      conditions account for only a minority of familial pancreatic cancers. Previous
      studies have identified an increased prevalence of noninvasive precursor lesions,
      including pancreatic intraepithelial neoplasia, in the pancreata of patients with
      a strong family history of pancreatic cancer. A detailed investigation of the
      histopathology of invasive familial pancreatic cancer could provide insights into
      the mechanisms responsible for familial pancreatic cancer, as well as aid early
      detection and treatment strategies. METHODS: We have conducted a blinded review
      of the pathology of 519 familial and 651 sporadic pancreatic cancers within the
      National Familial Pancreas Tumor Registry. Patients with familial pancreatic
      cancer were defined as individuals from families in which at least a pair of
      first-degree relatives have been diagnosed with pancreatic cancer. RESULTS:
      Overall, there were no statistically significant differences in histologic
      subtypes between familial and sporadic pancreatic cancers (p > 0.05). In
      addition, among surgical resection specimens within the study cohort, no
      statistically significant differences in mean tumor size, location, perineural
      invasion, angiolymphatic invasion, lymph node metastasis and pathologic stage
      were identified (p > 0.05). CONCLUSIONS: Similar to sporadic pancreatic cancer,
      familial pancreatic cancer is morphologically and prognostically a heterogeneous
      disease.

PMID- 25959246
TI  - Tumor associated antigens or anti-TAA autoantibodies as biomarkers in the
      diagnosis of ovarian cancer: a systematic review with meta-analysis.
AB  - OBJECTIVE: This systematic review aims to outline and summarize known tumor
      associated antigens (TAAs) or anti-TAA autoantibodies and their diagnostic values
      in ovarian cancer (OC). METHODS: A systematic literature search was conducted in
      two databases. Data were independently extracted and reviewed by two junior
      investigators and the disagreement was further resolved by consulting one of the
      senior investigators. RESULTS: Sixty publications reporting 113 different TAAs or
      anti-TAA autoantibodies were included. The majority of the studies were conducted
      in western countries. CA125, p53 and HE4 were the most frequently tested TAAs in
      OC. Meta-analysis showed that there was a significant association between serum
      anti-p53 autoantibody and increased risk of OC. CONCLUSION: Serum TAAs or anti
      TAA autoantibodies are promising diagnostic biomarkers in the detection of OC. A
      customized mini-array of multiple TAAs may enhance the detection of anti-TAA
      autoantibodies in OC. Additional studies with sufficient number of OC patients
      and carefully selected controls are needed to further verify the results.

PMID- 25959248
TI  - Unilateral Acute Closed-Angle Glaucoma After Elective Lumbar Surgery Reveals
      Multiple Intracranial Aneurysms. A Case Report and Discussion on Workup of
      Differential Diagnoses.
AB  - The purpose of our paper is to present a case of a rare complication of posterior
      lumbar surgery. Our patient presented for elective lumbar decompression, which
      was complicated by durotomy. She then developed sudden headache and right eye
      pain once upright on postoperative day 2. Then on postoperative day 3, she
      developed a dilated nonreactive pupil with extraocular movements intact. A
      computed tomography scan of the head was negative for subarachnoid hemorrhage.
      Magnetic resonance angiography showed a possible right posterior communicating
      artery aneurysm. She was transferred to a tertiary center with a severe headache
      and a nonreactive pupil, raising concern for evolving third nerve palsy due to
      aneurysm. A cerebral angiogram was performed and showed multiple aneurysms.
      Aneurysm location did not explain the patient's symptoms, and ophthalmology was
      consulted. Elevated intraocular pressure was noted, and the patient was diagnosed
      with acute angle-closure glaucoma (AACG). Our patient was medically treated and
      subsequently underwent laser peripheral iridotomy. She has had improved vision
      and pupillary function at 1 month follow-up. The diagnosis is complicated by a
      durotomy, which led to cascade in the differential diagnosis to rule out
      intracranial pathology. Her age and home medications, which had sympathomimetic
      effects, placed her at increased risk, but lying prone in the dark under the
      drapes was likely the lead causative factor. In conclusion, a postoperative
      posterior spine patient with eye pain and changes in vision and pupils should be
      evaluated with AACG in mind due to the devastating consequences if left untreated
      or treatment is delayed. 

PMID- 25959247
TI  - Cerebro-cerebellar Resting-State Functional Connectivity in Children and
      Adolescents with Autism Spectrum Disorder.
AB  - BACKGROUND: The cerebellum plays important roles in sensori-motor and supramodal
      cognitive functions. Cellular, volumetric, and functional abnormalities of the
      cerebellum have been found in autism spectrum disorders (ASD), but no
      comprehensive investigation of cerebro-cerebellar connectivity in ASD is
      available. METHODS: We used resting-state functional connectivity magnetic
      resonance imaging in 56 children and adolescents (28 subjects with ASD, 28
      typically developing subjects) 8-17 years old. Partial and total correlation
      analyses were performed for unilateral regions of interest (ROIs), distinguished
      in two broad domains as sensori-motor (premotor/primary motor, somatosensory,
      superior temporal, and occipital) and supramodal (prefrontal, posterior parietal,
      and inferior and middle temporal). RESULTS: There were three main findings: 1)
      Total correlation analyses showed predominant cerebro-cerebellar functional
      overconnectivity in the ASD group; 2) partial correlation analyses that
      emphasized domain specificity (sensori-motor vs. supramodal) indicated a pattern
      of robustly increased connectivity in the ASD group (compared with the typically
      developing group) for sensori-motor ROIs but predominantly reduced connectivity
      for supramodal ROIs; and 3) this atypical pattern of connectivity was supported
      by significantly increased noncanonical connections (between sensori-motor
      cerebral and supramodal cerebellar ROIs and vice versa) in the ASD group.
      CONCLUSIONS: Our findings indicate that sensori-motor intrinsic functional
      connectivity is atypically increased in ASD, at the expense of connectivity
      supporting cerebellar participation in supramodal cognition.

PMID- 25959249
TI  - Grisel Syndrome Following Adenoidectomy: Surgical Management in a Case with
      Delayed Diagnosis.
AB  - BACKGROUND: Grisel syndrome is a nontraumatic rotatory subluxation of the
      atlantoaxial joint, following nasopharyngeal inflammation or ear, nose, and
      throat (ENT) procedures. The syndrome should be suspected in cases of persistent
      neck pain and stiffness, especially after ENT surgical procedures. The primary
      treatment of early detected Grisel syndrome is conservative. If conservative
      treatment fails to achieve a stable reduction or it is followed by neurologic
      symptoms, arthrodesis of the first and second cervical vertebrae is indicated. We
      report the case of a 9-year-old boy who developed Grisel syndrome after
      adenoidectomy and was treated with C1-C3 internal fixation and fusion. CASE
      DESCRIPTION: A 9-year-old boy was referred to our hospital with a 3-month history
      of painful torticollis, which appeared 4 days after adenoidectomy. The patient
      underwent a neuroimaging study that documented the presence of atlantoaxial
      rotatory subluxation. The patient underwent C1-C3 internal fixation and fusion,
      using lateral masses and laminar and pars interarticularis screws. On the third
      postoperative day he was mobilized with a rigid collar. Postoperative computed
      tomography scans showed the resolution of rotational deformity and a solid
      fusion. CONCLUSION: Early treatment of Grisel syndrome is of utmost importance to
      avoid neurologic complications and surgical intervention. In a patient with
      torticollis following ENT procedures, Grisel syndrome should be always suspected.
      In case of failure of conservative treatment or in case of delayed diagnosis,
      rigid C1-C2 or C1-C2-C3 fixation is a straightforward and valid surgical
      technique, even in children, because it provides immediate spinal stability in
      all planes at the atlantoaxial complex, avoiding the need for prolonged rigid
      external bracing.

PMID- 25959251
TI  - Diagnosis of concomitant pituitary adenoma and Rathke's cleft cyst with magnetic
      resonance imaging.
AB  - INTRODUCTION: The diagnosis of concomitant pituitary adenoma (PA) and Rathke's
      cleft cyst (RCC) is difficult because PA and RCC cause similar symptoms. This
      study aimed to investigate magnetic resonance imaging (MRI) characteristics and
      surgical management of sellar lesions for concomitant PA and RCC. METHODS: A
      retrospective study was performed in 18 patients with concomitant PA and RCC who
      visited our hospital between June 2008 and May 2014. MRI features, surgical
      management, histopathological diagnosis and prognosis of concomitant PA and RCC
      were summarized. RESULTS: Of the 18 patients, 3 cases were diagnosed with
      concomitant PA and RCC and 2 with concomitant PA and intermedia cyst by
      preoperative MRI. The remaining 8 cases were misdiagnosed as cystic formation of
      PA, 3 cases were bleeding of PA, and 2 cases were RCC. Surgery via the trans
      sphenoidal route was performed in 17 cases and trans-frontal approach was chosen
      for one patient. All PAs resected were diagnosed by histological examination and
      the diagnosis of concomitant PA and RCC was histologically confirmed. CONCLUSION:
      A non-enhancing cyst-like structure within the pars intermedia of PA usually
      located in the midline is a prominent MRI feature of coexisted PA and RCC. Total
      resection of coexisted RCC must be achieved and fat graft should be avoided
      during surgery because of high recurrence rate of RCC and complicated
      hypophysitis.

PMID- 25959250
TI  - Hypermethylated Epidermal growth factor receptor (EGFR) promoter is associated
      with gastric cancer.
AB  - Epidermal growth factor receptor (EGFR) is a member of the receptor tyrosine
      kinases ErbB family and it is found to be overexpressed in gastric cancer.
      However, the mechanism of the regulation of the EGFR expression is still unknown.
      We used the Sequenom EpiTYPER assay to detect the methylation status of the EGFR
      promoter in normal and tumour tissues of 30 patients with gastric cancer. We also
      carried out quantitative real time PCR (qPCR) to detect the expression level of
      EGFR in our 30 patients. Notably, increased methylation level at EGFR promoter
      was found in tumour tissues than the corresponding adjacent noncancerous. In both
      Region I DMR and Region II DMR detected in our study, tumor tissues were
      significantly hypermethylated (P=2.7743E-10 and 2.1703E-05, respectively). Region
      I_?CpG_2 was also found to be associated with the presence of distant metastasis
      (P=0.0323). Furthermore, the results showed a strongly significant association
      between the relative EGFR expression and the EGFR methylation changes in both
      Region I and Region II (P=0.0004 and 0.0001, respectively). Our findings help to
      indicate the hypermethylation at EGFR promoter in gastric cancer and it could be
      a potential epigenetic biomarker for gastric cancer status and progression.

PMID- 25959252
TI  - Nijmegen breakage syndrome protein 1 (NBS1) modulates hypoxia inducible factor
      1alpha (HIF-1alpha) stability and promotes in vitro migration and invasion under
      ionizing radiation.
AB  - Hypoxia-inducible factor (HIF) is a heterodimer transcription factor complex that
      monitors the cellular response to the oxygen levels in cells. Hypoxia-inducible
      factor-1alpha (HIF-1alpha) has been shown to be stabilized by ionizing radiation
      (IR) and its stabilization promotes tumor progression and metastasis. Nijmegen
      breakage syndrome protein 1 (NBS1), a component of the MRE11-RAD50-NBS1 complex,
      plays an important role in the cellular response to DNA damage but its
      overexpression contributes to transformation and has been found to correlate with
      metastasis. However, whether NBS1 participates in IR-induced metastasis needs to
      be further determined. The aim of this study is to investigate whether radiation
      induced HIF-1alpha stabilization is regulated by NBS1 and thereby promotes tumor
      cell migration/invasion. Here, we show that both NBS1 and HIF-1alpha expression
      are up-regulated after exposure to IR, and NBS1 increases HIF-1alpha expression
      at the protein level. In addition, IR treatment promotes the epithelial
      mesenchymal transition (EMT) and in vitro cell migration and invasion activity,
      which could be abolished by suppression of NBS1. Furthermore, NBS1 directly
      interacts with HIF-1alpha and reduces the ubiquitination of HIF-1alpha? Co
      expression of HIF-1alpha and NBS1 in primary tumors of patients with lung
      adenocarcinoma correlates with a worse prognosis. These results provide a new
      function of NBS1 in stabilizing HIF-1alpha under IR, which leads to enhanced
      cancer cell migration and invasion. 

PMID- 25959253
TI  - Determination of aflatoxin M1 in breast milk as a biomarker of maternal and
      infant exposure in Colombia.
AB  - Chronic exposure to aflatoxins, and especially to aflatoxin B1 (AFB1), causes
      hepatocellular carcinoma with prevalence 16-32 times higher in developing
      compared with developed countries. Aflatoxin M1 (AFM1) is a monohydroxylated
      metabolite from AFB1 that is secreted in milk and which can be used as a
      biomarker of AFB1 exposure. This study aimed to determine AFM1 levels in human
      breast milk using immunoaffinity column clean-up with HPLC and fluorescence
      detection. Breast milk samples were obtained from 50 nursing mothers. Volunteers
      filled in a questionnaire giving their consent to analyse their samples as well
      as details of their socioeconomic, demographic and clinical data. The possible
      dietary sources of aflatoxins were assessed using a food frequency questionnaire.
      A total of 90% of the samples tested positive for AFM1, with a mean of 5.2 ng l(
      1) and a range of 0.9-18.5 ng l(-1). The study demonstrated a high frequency of
      exposure of mothers and neonates to AFB1 and AFM1 in Colombia, and it points out
      the need to regulate and monitor continuously the presence of aflatoxins in human
      foods. Further research is needed in order to determine the presence of other
      mycotoxins in foods and in human samples as well as to devise protection
      strategies in a country where mycotoxins in human foods are commonly found.

PMID- 25959254
TI  - Impaired toll-like receptor signalling in peripheral B cells from newly diagnosed
      type-2 diabetic subjects.
AB  - Toll-like receptors (TLRs) under diabetic conditions trigger inflammation and
      impair immunity. In the present study, we looked at the expression of TLRs (2 and
      4) and their adaptors in Normal Glucose Tolerant (NGT), Newly Diagnosed Type-2
      Diabetic (NDD) and Known Type-2 Diabetic (KDM) subjects. We also estimated TLR
      induced cytokine secretion, cellular activation and apoptosis. Surface expression
      of TLR2 and 4 was significantly reduced in the B cells of the NDD subjects and
      was associated with decreased cellular activation and cytokine secretion (TNF
      alpha and IL-6). This impairment was not due to B cell deficiency or apoptosis or
      immunosuppressive cytokine (IL-10 and TGF-beta) secretion. However, the
      upregulation of immunomodulatory enzymes (Arg-1, HO-1 and IDO) could probably
      account for the reduced TLR expression. The defective TLR signalling was largely
      ameliorated in the KDM group which might be due to the use the anti-diabetic
      drugs which have anti-inflammatory effect. 

PMID- 25959255
TI  - Antifibrotic effect of lysophosphatidic acid receptors LPA1 and LPA3 antagonist
      on experimental murine scleroderma induced by bleomycin.
AB  - The study of lysophosphatidic acid (LPA) receptor has recently focused on its
      involvement in the pathogenesis of systemic sclerosis (SSc). We examined the
      inhibitory effects of the antagonist for the LPA receptor, a selective LPA1 and
      LPA3 antagonist (Ki16425), on dermal and lung fibrosis in a mouse model of SSc.
      Ki16425 was administered intra-dermally after 6 h on the same sites as bleomycin
      injection. Histopathological examination showed that skin lesions were markedly
      attenuated by treatment with Ki16425 at doses of 1 and 10 mg/kg, along with
      reduced dermal thickness. Hydroxyproline contents in the Ki16425-treated skin
      showed a decrease of 35% (1 mg/kg) and 45% (10 mg/kg) compared with those in the
      oil-injected skin of the controls. The number of mast cells and phospho-Smad2/3
      positive spindle cells of the Ki16425-treated skin was significantly decreased
      compared with that in the controls. Additionally, RT-PCR analysis showed that the
      mRNA levels of TGF-beta1, CTGF, MIP-1alpha, IFN-gamma and collagen alpha1(I) were
      significantly decreased in both the 1-mg/kg and 10-mg/kg groups of the Ki16425
      treated mice compared with those in the controls. Furthermore, treatment with
      bleomycin and Ki16425 showed reduction in lung fibrosis, and the hydroxyproline
      contents in the lungs of the Ki16425-treated mice showed a decrease of 25% (1
      mg/kg) and 32% (10 mg/kg) compared with those in the lungs of the controls. Taken
      together, Ki16425 was found to improve dermal and lung fibrosis in a mouse model
      of bleomycin-induced murine scleroderma. These results suggest that Ki16425 has
      the potential to be an effective new treatment for scleroderma. 

PMID- 25959256
TI  - Stunning fish with CO2 or electricity: contradictory results on behavioural and
      physiological stress responses.
AB  - Studies that address fish welfare before slaughter have concluded that many of
      the traditional systems used to stun fish including CO2 narcosis are unacceptable
      as they cause avoidable stress before death. One system recommended as a better
      alternative is electrical stunning, however, the welfare aspects of this method
      are not yet fully understood. To assess welfare in aquaculture both behavioural
      and physiological measurements have been used, but few studies have examined the
      relationship between these variables. In an on-site study aversive behaviours and
      several physiological stress indicators, including plasma levels of cortisol and
      ions as well as blood physiological variables, were compared in Arctic char
      (Salvelinus alpinus) stunned with CO2 or electricity. Exposure to water saturated
      with CO2 triggered aversive struggling and escape responses for several minutes
      before immobilization, whereas in fish exposed to an electric current
      immobilization was close to instant. On average, it took 5 min for the fish to
      recover from electrical stunning, whereas fish stunned with CO2 did not recover.
      Despite this, the electrically stunned fish had more than double the plasma
      levels of cortisol compared with fish stunned with CO2. This result is surprising
      considering that the behavioural reactions were much more pronounced following
      CO2 exposure. These contradictory results are discussed with regard to animal
      welfare and stress physiological responses. The present results emphasise the
      importance of using an integrative and interdisciplinary approach and to include
      both behavioural and physiological stress indicators in order to make accurate
      welfare assessments of fish in aquaculture. 

PMID- 25959258
TI  - Preliminary findings on the effect of melatonin on the clinical outcome of
      cataract surgery in dogs.
AB  - OBJECTIVE: Cataract is the most prevalent cause of blindness in dogs.
      Phacoemulsification (PE) is currently the surgical treatment of choice to remove
      the opaque lens; however, it is associated with varying degrees of postoperative
      inflammation. We assessed the effect of melatonin on postoperative complications
      of canine cataract surgery. ANIMAL STUDIED: Eleven diabetic and thirteen healthy
      owned dogs with cataracts. PROCEDURES: All dogs underwent cataract surgery by PE.
      The anti-inflammatory effect of melatonin was compared with the reference
      treatments: nonsteroidal anti-inflammatory drugs (NSAIDs) for diabetic dogs, and
      dexamethasone for nondiabetic dogs. Eyes were examined by means of clinical
      evaluation and intraocular pressure (IOP). RESULTS: In diabetic dogs, melatonin
      was more effective than topical and systemic NSAIDs in reducing the clinical
      score at 2, 7, and 20 days postsurgery, while it showed a similar efficacy to
      topical dexamethasone in dogs with hereditary cataracts. IOP decreased in all
      groups at 2 days postsurgery, but this decrease reached statistical significance
      only in diabetic dogs treated with NSAIDs, and persisted at 7 days postsurgery in
      this group. Afterward, IOP returned to normal values in all groups. Melatonin
      decreased the occurrence of surgical sequelae in diabetic and nondiabetic dogs.
      CONCLUSIONS: These results indicate that melatonin might constitute a useful tool
      for reducing postoperative PE complications in dogs.

PMID- 25959257
TI  - Inhibition of Human Neutrophil Responses by the Essential Oil of Artemisia
      kotuchovii and Its Constituents.
AB  - Essential oils were obtained by hydrodistillation of the flowers+leaves and stems
      of Artemisia kotuchovii Kupr. (AKEO(f+l) and AKEO(stm), respectively) and
      analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC
      MS). The primary components of the oils were estragole, (E)- and (Z)-beta
      ocimenes, methyleugenol, limonene, spathulenol, beta-pinene, myrcene, and (E)
      methyl cinnamate. Seventy-four constituents were present at concentrations from
      0.1 to 1.0%, and 34 compounds were identified in trace (<0.1%) amounts in one or
      both plant components. Screening of the essential oils for biological activity
      showed that AKEO(stm), but not AKEOf+l, inhibited N-formyl-Met-Leu-Phe (fMLF)
      stimulated Ca(2+) flux and chemotaxis and phorbol-12-myristate-13-acetate (PMA)
      induced reactive oxygen species (ROS) production in human neutrophils. Selected
      pure constituents, representing >96% of the AKEO(stm) composition, were also
      tested in human neutrophils and HL-60 cells transfected with N-formyl peptide
      receptor 1 (FPR1). One component, 6-methyl-3,5-heptadien-2-one (MHDO), inhibited
      fMLF- and interleukin 8 (IL-8)-stimulated Ca(2+) flux, fMLF-induced chemotaxis,
      and PMA-induced ROS production in human neutrophils. MHDO also inhibited fMLF
      induced Ca(2+) flux in FPR1-HL60 cells. These results suggest that MHDO may be
      effective in modulating some innate immune responses, possibly by inhibition of
      neutrophil migration and ROS production.

PMID- 25959259
TI  - Laser surgery as a treatment for histologically confirmed sarcoids in the horse.
AB  - REASONS FOR PERFORMING STUDY: Laser resection for the treatment of sarcoids is an
      established part of equine practice; however, few studies have provided long-term
      follow-up results. Additionally, many previous reports have evaluated several
      treatments concurrently or have not been able to provide a definitive
      histological diagnosis of sarcoid. OBJECTIVES: To establish the success rate
      following laser resection as a sole treatment for histologically confirmed
      sarcoids and evaluate risk factors for recurrence. STUDY DESIGN: Retrospective
      time-to-event analysis. METHODS: Horses included had laser surgery to remove at
      least one sarcoid between 1 July 2005 and 1 September 2012. No previous
      known/concurrent veterinary treatment was administered. Diagnosis was confirmed
      by histology in all cases. Clinical data were retrieved from the hospital
      database. Follow-up information was obtained by telephone questionnaire. RESULTS:
      Ninety-nine horses, with a total of 235 sarcoids, were included in the analysis;
      82 (83%) had no recurrence of the sarcoid removed and 71 (72%) had no occurrence
      of any sarcoids following surgery. Horses with sarcoids on the head and neck and
      those with verrucose sarcoids were at increased risk of recurrence (hazard ratios
      of 1.61 and 4.03, and 95% confidence intervals of 1.02-2.56 and 1.11-14.7,
      respectively). CONCLUSIONS: Laser resection of sarcoids in the horse has a
      positive post operative prognosis. Further work is required to fully evaluate
      risk factors for recurrence fully.

PMID- 25959260
TI  - The longitudinal relationship between quality of life and survival in advanced
      stage cancer.
AB  - OBJECTIVES: Quality of Life (QoL) at baseline is frequently found to be a
      prognostic factor in cancer studies. However, little is known about the
      relationship of the trajectory of QoL and survival in patients with advanced
      cancer. This study evaluates the effects of both level and change of QoL on
      survival to explore the potential of utilizing longitudinal information of QoL
      for prognosis. METHODS: A series of joint models were used in a sample (N = 512)
      of patients diagnosed with advanced cancer (sample consisted of nine different
      cancer sites) with assessments of QoL across six time points and with survival
      information recorded up to 28 months after diagnosis. We used FACT-G as the QoL
      measure, and we evaluated the effects of change in QoL controlling for the time
      dependent effects of chemotherapy and radiation. RESULTS: The median survival for
      patients was 14.2 months, and 10% of the sample had survived beyond 28 months
      after the diagnosis of advanced cancer. The effect of change of QoL on survival
      was significant (hazard ratio = 0.98; p < 0.001) controlling for time-dependent
      treatment effects. Also, the slope of the trajectory in QoL was found to be a
      significant predictor of survival (hazard ratio = 0.18; p < 0.001). CONCLUSION:
      These preliminary findings suggest that the patient's longitudinal experience in
      QoL may be a significant prognostic factor of survival, a novel finding with
      potentially important implications in medical decision making. Longitudinal
      information on QoL can be used for updating the patient's prognosis of survival.

PMID- 25959261
TI  - Effect of heart rate on the intrinsic and the ventricular-paced QRS duration.
AB  - BACKGROUND: We evaluated the effect of heart rate on the intrinsic and the
      ventricular-paced QRS duration in implanted device recipients with normal or
      reduced left ventricular ejection fraction (EF). METHODS: We studied 239
      outpatients with preserved intrinsic ventricular activation and normal (n=92) or
      reduced (n=147) EF who had apical (RVA) or mid-septal (RVS) right ventricular
      lead position. The QRS duration was measured at baseline and during atrial-based
      pacing at increased heart rate to ensure intrinsic or ventricular-paced QRS
      activation. RESULTS: The heart rate increase shortened the intrinsic QRS only in
      patients with normal EF, and further prolonged the ventricular-paced QRS in
      patients with reduced EF and either narrow or wide QRS (p<0.001), irrespective of
      RVA or RVS pacing (p<0.01). CONCLUSION: Heart rate increase is associated with
      further QRS prolongation in patients with reduced EF, regardless of RVA or RVS
      pacing site.

PMID- 25959262
TI  - A wide QRS/T angle in bundle branch blocks is associated with increased risk for
      coronary heart disease and all-cause mortality in the Atherosclerosis Risk in
      Communities (ARIC) Study.
AB  - BACKGROUND: Repolarization abnormality in bundle branch blocks (BBB) is
      traditionally ignored. This study evaluated the prognostic value of QRS/T angle
      for mortality in the presence and absence of BBB. METHODS AND RESULTS: Total
      15,408 participants (mean age 54 years, 55.2% women, 26.9% blacks, 2.8% with BBB)
      were from the Arteriosclerosis Risk in Communities Study. Sex stratified Cox
      regression models were used to compute hazard ratios (HRs) with 95% confidence
      intervals (CIs) for coronary heart disease (CHD) and all-cause mortality for wide
      spatial QRS/T angle with and without BBB including right BBB (RBBB), left BBB
      (LBBB) and indetermined-type ventricular conduction defect (IVCD) and RBBB
      combined with left anterior fascicular block. During a median 22-year follow-up,
      4767 deaths occurred, 728 of them CHD deaths. Using the No-BBB with QRS/T angle
      below median value as gender-specific reference groups, the mortality risk
      increase was significant for both women and men with No-BBB and QRS/T angle above
      the median value. In the pooled ICVD/LBBB group, the risk for CHD death was
      increased 15.9-fold in women and 6.04 fold in men, and for all-cause deaths 3.01
      fold in women and 1.84-fold in men. However, the mortality risk in isolated RBBB
      group was only significantly increased in women but not in men. CONCLUSION: A
      wide spatial QRS/T angle in BBB is associated with increased risk for CHD and all
      cause mortality over and above the predictive value for BBB alone. The risk for
      women is as high as or higher than that in men.

PMID- 25959263
TI  - Influence of QRS infarct score and QRS duration prior to transcatheter aortic
      valve replacement on follow-up left ventricular end systolic volume in patients
      with new persistent left bundle branch block.
AB  - BACKGROUND: New-onset left bundle branch block (LBBB) is a known complication
      during Transcatheter Aortic Valve Replacement (TAVR). This study evaluated the
      influence of pre-TAVR cardiac conditions on left ventricular functions in
      patients with new persistent LBBB post-TAVR. METHODS: Only 11 patients qualified
      for this study because of the strict inclusion criteria. Pre-TAVR
      electrocardiograms were evaluated for Selvester QRS infarct score and QRS
      duration, and left ventricular end-systolic volume (LVESV) was used as outcome
      variable. RESULTS: There was a trend towards a positive correlation between QRS
      score and LVESV of r=0.59 (p=0.058), while there was no relationship between QRS
      duration and LVESV (r=-0.18 [p=0.59]). CONCLUSION: This study showed that
      patients with new LBBB and higher pre-TAVR QRS infarct score may have worse post
      TAVR left ventricular function, however, pre-TAVR QRS duration has no such
      predictive value. Because of the small sample size these results should be
      interpreted with caution and assessed in a larger study population.

PMID- 25959264
TI  - Longitudinal linkages between posttraumatic stress disorder and posttraumatic
      growth in adolescent survivors following the Wenchuan earthquake in China: A
      three-wave, cross-lagged study.
AB  - The aim of this study is to examine the longitudinal relationships between
      posttraumatic stress disorder (PTSD) and posttraumatic growth (PTG) among
      adolescent survivors of the 2008 Wenchuan earthquake in China. The participants
      in our study included 245 adolescent survivors who were randomly selected from
      several primary and secondary schools in the counties of Wenchuan, which are the
      areas most severely affected by the Wenchuan earthquake. Participants completed
      the Revised Child PTSD Symptom Scale and the Posttraumatic Growth Inventory
      (PTGI) at 3.5 years after the earthquake (T1), 4.5 years after the earthquake
      (T2), and 5.5 years after the earthquake (T3). The results found that PTSD
      reported in T1 and T2 predicted subsequent PTG reported at T2 and T3 and that PTG
      did not predict PTSD from T1 to T3. In addition, the cross-sectional correlation
      between PTSD and PTG weakened from T1 to T3. These results indicate that PTSD and
      PTG can coexist in individuals after a traumatic experience, and they further
      suggest that the reduction in PTSD does not indicate the appearance of PTG. 

PMID- 25959265
TI  - Pathological Internet use among adolescents: Comparing gamers and non-gamers.
AB  - "Internet gaming disorder" was recently included in Section 3 of the Diagnostic
      and Statistical Manual of Mental Disorders (DSM-5). Non-gaming Internet
      activities were not considered because of a lack of evidence. This study examined
      whether gamers differ from non-gamers with respect to their psychological well
      being among students who show pathological Internet use (PIU). This cross
      sectional study was conducted within the project "Working in Europe to Stop
      Truancy Among Youth (WE-STAY)". A total of 8807 European representative students
      from randomly selected schools were included. The Young Diagnostic Questionnaire
      was applied to assess PIU, and students with this condition were divided into
      gamers (PIU-G) and non-gamers (PIU-NG). Overall, 3.62% and 3.11% of the students
      were classified as having PIU-G and PIU-NG, respectively. A multinomial logistic
      regression revealed that students with PIU-G and those with PIU-NG showed
      similarly increased risks for emotional symptoms, conduct disorder,
      hyperactivity/inattention, self-injurious behaviors, and suicidal ideation and
      behaviors. Students with PIU-G were more likely to be male and have a higher risk
      for peer problems than those with PIU-NG. Students with PIU-NG had a higher risk
      of depression than those with PIU-G. The significant psychological impairment of
      PIU-NG suggests that it should be considered in future diagnostic criteria. 

PMID- 25959267
TI  - Visual detection of goose haemorrhagic polyomavirus in geese and ducks by loop
      mediated isothermal amplification.
AB  - Goose haemorrhagic polyomavirus (GHPV) is an aetiological agent of haemorrhagic
      nephritis and enteritis of geese occurring in geese (Anser anser). GHPV may also
      infect Muscovy ducks (Carina mochata) and mule ducks. Early detection of GHPV is
      important to isolate the infected birds from the rest of the flock thus limiting
      infection transmission. The current diagnosis of haemorrhagic nephritis and
      enteritis of geese is based on virus isolation, histopathological examination,
      haemagglutination inhibition assay, ELISA and polymerase chain reaction (PCR).
      Recently, real-time PCR assay was developed which considerably improved detection
      of GHPV. In spite of many advantages, these methods are still time-consuming and
      inaccessible for laboratories with limited access to ELISA plate readers or PCR
      thermocyclers. The aim of our study was to develop loop-mediated isothermal
      amplification (LAMP) that may be conducted in a water bath. Two pairs of specific
      primers complementary to VP1 gene of GHPV were designed. The results of GHPV LAMP
      were recorded under ultraviolet light. Our study showed LAMP was able to
      specifically amplify VP1 fragment of a GHPV without cross-reactivity with other
      pathogens of geese and ducks. LAMP detected as little as 1.5 pg of DNA extracted
      from a GHPV standard strain (150 pg/ul). The optimized LAMP was used to examine
      18 field specimens collected from dead and clinically diseased geese and ducks
      aged from 1 to 12 weeks. The positive signal for GHPV was detected in three out
      of 18 (16.6%) specimens. These results were reproducible and consistent with
      those of four real-time PCR. To the best of our knowledge this is the first
      report on LAMP application for the GHPV detection. 

PMID- 25959266
TI  - Variable clinical expression in patients with mosaicism for KCNQ2 mutations.
AB  - Mutations in the KCNQ2 gene, encoding a potassium channel subunit, were reported
      in patients presenting epileptic phenotypes of varying severity. Patients
      affected by benign familial neonatal epilepsy (BFNE) are at the milder end of the
      spectrum, they are affected by early onset epilepsy but their subsequent
      neurological development is usually normal. Mutations causing BFNE are often
      inherited from affected parents. Early infantile epileptic encephalopathy type 7
      (EIEE7) is at the other end of the severity spectrum and, although EIEE7 patients
      have early onset epilepsy too, their neurological development is impaired and
      they will present motor and intellectual deficiency. EIEE7 mutations occur de
      novo. Electrophysiological experiments suggested a correlation between the type
      of mutation and the severity of the disease but intra and interfamilial
      heterogeneity exist. Here, we describe the identification of KCNQ2 mutation
      carriers who had children affected with a severe epileptic phenotype, and found
      that these individuals were mosaic for the KCNQ2 mutation. These findings have
      important consequences for genetic counseling and indicate that neurological
      development can be normal in the presence of somatic mosaicism for a KCNQ2
      mutation.

PMID- 25959268
TI  - [Kinesiotherapy effect on quality of life, sexual function and climacteric
      symptoms in women with fibromyalgia].
AB  - OBJECTIVE: To evaluate the effect of the kinesiotherapy in the quality of life,
      sexual function and menopause-related symptoms and compare in climacteric women
      with and without fibromyalgia (FM). METHODOLOGY: the group was composed of 90
      climacteric women divided in 2 groups: FM (47) and control (43). The patients
      were analyzed on their quality of life (Utian Quality of Life [UQoL]), sexual
      function (Sexual Quotient-Female Version [SQ-F] questionnaire) and intensity of
      the climacteric symptoms (Blatt-Kupperman menopausal index [BKMI]). Both groups
      performed pelvic floor kinesiotherapy, composed of 20 sessions, twice a week.
      Statistical analysis was performed using Student's t-test, mixed-design analysis
      of variance (ANOVA) and Cohen's Kappa. RESULTS: In the quality of life, an
      improvement was noticed in both groups for all domains analyzed. In the
      comparison between groups it was noticed a difference in the emotional (p=0.01),
      health (p=0.03) and sexual (p=0.001) domains with considerable gains verified in
      the control group. Improvement was also noticed in the sexual function. In the
      analysis between groups, FM group showed a lower score compared to the control
      group (p < 0.001). With respect to the climacteric symptoms, there was no
      difference in the analysis between groups after the intervention (p < 0.001).
      CONCLUSIONS: The pelvic floor kinesiotherapy promotes a positive effect in the
      domains of quality of life, sexual function and climacteric symptoms in women
      with and without fibromyalgia in the climacteric period; however, fibromyalgia
      seems to be a limiting factor to achieve better results in some of the aspects
      evaluated.

PMID- 25959269
TI  - Cortical auditory evoked potentials as an objective measure of behavioral
      thresholds in cochlear implant users.
AB  - The aim of this study was to assess the suitability of using cortical auditory
      evoked potentials (CAEPs) as an objective tool for predicting behavioral hearing
      thresholds in cochlear implant (CI) users. Nine experienced adult CI users of
      Cochlear(TM) devices participated. Behavioral thresholds were measured in CI
      users across apical, mid and basal electrodes. CAEPs were measured for the same
      stimuli (50 ms pulse trains of 900-pps rate) at a range of input levels across
      the individual's psychophysical dynamic range (DR). Amplitude growth functions
      using global field power (GFP) were plotted, and from this the CAEP thresholds
      were extrapolated and compared to the behavioral thresholds. Increased amplitude
      and decreased latency of the N1-P2 response was seen with increasing input level.
      A strong correlation was found between CAEP and behavioral thresholds (r = 0.93),
      implying that the cortical response may be more useful as an objective
      programming tool for cochlear implants than the auditory nerve response. 

PMID- 25959270
TI  - Simultaneous suppression of tone burst-evoked otoacoustic emissions: Two and
      three-tone burst combinations.
AB  - Previous investigations have shown that components of a tone burst-evoked
      otoacoustic emission (TBOAE) evoked by a 1 kHz tone burst (TB1) can be suppressed
      by the simultaneous presence of a 2 kHz tone burst (TB2) or a pair of tone bursts
      at 2 and 3 kHz (TB2 and TB3 respectively). No previous study has measured this
      "simultaneous suppression of TBOAEs" for both TB2 alone and TB2 and TB3 from the
      same ears, so that the effect of the additional presence of TB3 on suppression
      caused by TB2 is not known. In simple terms, three outcomes are possible;
      suppression increases, suppression is reduced or suppression is not affected.
      Comparison of previously reported simultaneous suppression data suggests TB3
      causes a reduction in suppression, though it is not clear if this is a genuine
      effect or simply reflects methodological and ear differences between studies.
      This issue has implications for previously proposed mechanisms of simultaneous
      suppression of TBOAEs and the interpretation of clinical data, and is clarified
      by the present study. Simultaneous suppression of TBOAEs was measured for TB1 and
      TB2 as well as TB1, TB2 and TB3 at 50, 60 and 70 dB p.e. SPL from nine normal
      human ears. Results showed no significant difference between mean suppression
      obtained for the two and three-tone burst combinations, indicating the reduction
      of suppression inferred from comparison of previous data is likely a result of
      methodological and ear differences rather than a genuine effect. 

PMID- 25959272
TI  - EGFR and MEK Blockade in Triple Negative Breast Cancer Cells.
AB  - Although evidence suggests that the RAF/MEK/ERK pathway plays an important role
      in triple negative breast cancer (TNBC), resistance to MEK inhibitors has been
      observed in TNBC cells. Different mechanisms have been hypothesized to be
      involved in this phenomenon, including receptor tyrosine kinase-dependent
      activation of the PI3K/AKT pathway. In this study, we analyzed the effects of the
      MEK1/2 inhibitor selumetinib in combination with the epidermal growth factor
      receptor (EGFR) tyrosine kinase inhibitor gefitinib in a panel of TNBC cell lines
      that showed different levels of sensitivity to single-agent selumetinib: SUM-149
      and MDA-MB-231 cells resulted to be sensitive, whereas SUM-159, MDA-MB-468 and
      HCC70 cells were relatively resistant to the drug. Treatment of TNBC cells with
      selumetinib produced an increase of the phosphorylation of the EGFR both in
      selumetinib-sensitive SUM-149, MDA-MB-231 and in selumetinib-resistant MDA-MB-468
      TNBC cells. The combination of selumetinib and gefitinib resulted in a
      synergistic growth inhibitory effect in all the TNBC cell lines, although the
      IC50 was not reached in SUM-159 and MDA-MB-468 cells. This effect was associated
      with an almost complete suppression of ERK1/2 activation and a reduction of
      selumetinib-induced AKT phosphorylation. In addition, in selumetinib-sensitive
      TNBC cells the combination of selumetinib and gefitinib induced a significant
      G0/G1 cell cycle arrest and apoptosis. Taken together, our data demonstrated that
      blockade of the EGFR might efficiently increase the antitumor activity of
      selumetinib in a subgroup of TNBC and that this phenomenon might be related to
      the effects of such combination on both ERK1/2 and AKT activation.

PMID- 25959273
TI  - Diaryliodoniums by Rhodium(III)-Catalyzed C-H Activation: Mild Synthesis and
      Diversified Functionalizations.
AB  - Diaryliodonium salts play an increasingly important role as an aryl source.
      Reported is the first synthesis of diaryliodoniums by rhodium(III)-catalyzed C-H
      hyperiodination of electron-poor arenes under chelation assistance. This C-I
      coupling reaction occurred at room temperature with high regio-selectivity and
      functional-group compatibility. Subsequent diversified nucleophilic
      functionalization of a diaryliodonium allowed facile construction of C-C, C-N, C
      O, C-S, C-P and C-Br bonds, and in all cases the initial functionalization
      occurred at the arene containing the chelating-group.

PMID- 25959274
TI  - Exploring the effects of the size of reduced graphene oxide nanosheets for Pt
      catalyzed electrode reactions.
AB  - Pt-supported reduced graphene oxide (Pt/RGO) catalysts were prepared over the RGO
      sheets with different sizes for methanol oxidation and oxygen reduction reactions
      in acidic media. The Pt on the smaller RGO presented higher catalytic activities
      than the Pt on the larger RGO and the commercial Pt/C catalyst. 

PMID- 25959271
TI  - Effect of mineralocorticoid receptor blockade on hippocampal-dependent memory in
      adults with obesity.
AB  - OBJECTIVE: The hippocampus is crucial for paired-associate learning. Obesity is
      associated with increased mineralocorticoid receptor (MR) activity in peripheral
      and possibly central tissues, decreased hippocampal size in humans, and impaired
      hippocampal learning in rodents. The MR is expressed in hippocampal neurons, and
      MR blockade improves hippocampal learning in obese animals. The goal of the study
      was to determine whether MR blockade would modulate paired-associate learning in
      men and women with obesity. METHODS: Men and women ages 20-61 years with BMI
      between 30-45 kg/m(2) were randomly assigned to placebo (n = 11; 7 women) or 50
      mg spironolactone daily (n = 12; 7 women) for six weeks. At baseline and post
      treatment, subjects underwent a clinical and hormonal evaluation. They also
      underwent a computerized task that assesses paired-associate learning and has
      been shown by functional magnetic resonance imaging to activate the hippocampus.
      RESULTS: In an ANCOVA model that adjusted for baseline paired-associate learning,
      age, and race, spironolactone treatment was associated with a significant (P =
      0.043) improvement in hippocampal memory as compared to placebo treatment.
      CONCLUSIONS: Our findings demonstrate, for the first time, that blocking MR with
      chronic, low-dose spironolactone treatment improves paired-associate learning in
      individuals with obesity, suggesting that MR activation contributes to
      hippocampal memory modulation in humans.

PMID- 25959275
TI  - Factors affecting the choice of health specialty by medical graduates.

PMID- 25959276
TI  - The effect of syncope on the career choices of medical students.

PMID- 25959277
TI  - What factors influence British medical students' career intentions? A primary
      care response.

PMID- 25959278
TI  - Using Medical Admissions Units (MAU) for undergraduate teaching.

PMID- 25959279
TI  - RE: "What factors influence British medical students' career intentions?"
      Location and social relationships.

PMID- 25959280
TI  - Is problem-based learning an experimentation platform in Chinese medical schools?

PMID- 25959281
TI  - Gut feeling: Can it be taught?

PMID- 25959282
TI  - Clinical presentation of hyperthyroidism in a large representative sample of
      outpatients in France: relationships with age, aetiology and hormonal parameters.
AB  - OBJECTIVE: Signs and symptoms of thyrotoxicosis are not specific, and thyroid
      function tests are frequently prescribed to recognize such thyroid dysfunction.
      Ultrasensitive assays of thyroid-stimulating hormone (TSH) allow early diagnosis
      and identification of mild hyperthyroidism (generally designed as 'subclinical').
      The aim of this study was to re-evaluate the clinical picture of thyrotoxicosis
      in the context of the current large utilization of ultrasensitive TSH assays.
      DESIGN: Prospective descriptive cohort. METHODS: Clinical presentation of 1572
      patients with a recent (<3 months) diagnosis of thyrotoxicosis recruited by a
      large representative sample of 263 French endocrinologists was studied using two
      questionnaires (one at inclusion and the second after 3 months) concerning
      symptoms, hormonal evaluation and treatment. RESULTS: A total of 1240 (78.9%)
      patients were women, mean age 48 +/- 17 years. Subclinical hyperthyroidism (SCHT)
      was present in 86 patients (10.4%). Symptoms of thyrotoxicosis were in decreasing
      frequency order: palpitations, weakness, heat-related signs and disturbed sleep.
      A total of 64.9% of patients had lost weight. Signs and symptoms were more
      frequent in Graves' disease, in young patients, and were partially related to
      biochemical severity. Symptoms were less frequent in elderly patients except for
      cardiac manifestations (atrial fibrillation). Most patients with SCHT had one or
      several signs or symptoms of thyrotoxicosis. CONCLUSION: This study confirms that
      elderly patients have less symptoms of thyrotoxicosis than younger subjects but
      are at increased risk of cardiac complications. Our results show that most
      patients with 'subclinical' HT have in fact signs or symptoms of thyrotoxicosis.

PMID- 25959283
TI  - Enhanced magnetorheological performance of highly uniform magnetic carbon
      nanoparticles.
AB  - Magnetic carbon nanoparticles (MC NPs) are prepared on a multi-gram scale through
      carbonization of iron-doped polypyrrole nanoparticles (PPy NPs). Three different
      sized MC NPs (ca. 40, 60 and 90 nm) are prepared and adopted as dispersing
      materials for magnetorheological (MR) fluids to investigate the influence of
      particle size on MR properties. The MC NP-based MR fluids exhibit outstanding MR
      performances compared to the conventional magnetic carbon material-based fluids.
      In addition, the MR activities are enhanced with decreasing particle diameter and
      increasing applied magnetic field strength. Furthermore, anti-sedimentation
      properties are examined in order to achieve in-depth insight into the effect of
      the particle size on MR fluids. 

PMID- 25959284
TI  - Measurements of Intra-Aortic Balloon Wall Movement During Inflation and
      Deflation: Effects of Angulation.
AB  - The intra-aortic balloon pump (IABP) is a ventricular assist device that is used
      with a broad range of pre-, intra-, and postoperative patients undergoing cardiac
      surgery. Although the clinical efficacy of the IABP is well documented, the
      question of reduced efficacy when patients are nursed in the semi-recumbent
      position remains outstanding. The aim of the present work is therefore to
      investigate the underlying mechanics responsible for the loss of IABP performance
      when operated at an angle to the horizontal. Simultaneous recordings of balloon
      wall movement, providing an estimate of its diameter (D), and fluid pressure were
      taken at three sites along the intra-aortic balloon (IAB) at 0 and 45 degrees .
      Flow rate, used for the calculation of displaced volume, was also recorded distal
      to the tip of the balloon. An in vitro experimental setup was used, featuring
      physiological impedances on either side of the IAB ends. IAB inflation at an
      angle of 45 degrees  showed that D increases at the tip of the IAB first,
      presenting a resistance to the flow displaced away from the tip of the balloon.
      The duration of inflation decreased by 15.5%, the inflation pressure pulse
      decreased by 9.6%, and volume decreased by 2.5%. Similarly, changing the position
      of the balloon from 0 to 45 degrees , the balloon deflation became slower by 35%,
      deflation pressure pulse decreased by 14.7%, and volume suctioned was decreased
      by 15.2%. IAB wall movement showed that operating at 45 degrees  results in
      slower deflation compared with 0 degrees . Slow wall movement, and changes in
      inflation and deflation onsets, result in a decreased volume displacement and
      pressure pulse generation. Operating the balloon at an angle to the horizontal,
      which is the preferred nursing position in intensive care units, results in
      reduced IAB inflation and deflation performance, possibly compromising its
      clinical benefits. 

PMID- 25959285
TI  - Professor Yukio Fukuyama.

PMID- 25959286
TI  - Chorea as the initial manifestation of Sjogren syndrome.

PMID- 25959287
TI  - (1)H NMR brain metabonomics of scrapie exposed sheep.
AB  - While neurochemical metabolite modifications, determined by different techniques,
      have been diffusely reported in human and mice brains affected by transmissible
      spongiform encephalopathies (TSEs), this aspect has been little studied in the
      natural animal hosts with the same pathological conditions so far. Herein, we
      investigated, by high resolution (1)H NMR spectroscopy and multivariate
      statistical data analysis, the brain metabolite profile of sheep exposed to a
      scrapie agent in a naturally affected flock. On the basis of clinical
      examinations and western blotting analysis for the pathological prion protein
      (PrP(Sc)) in brain tissues, sheep were catalogued as not infected (H), infected
      with clinical signs (S), and infected without clinical signs (A). By discriminant
      analysis of spectral data, comparing S vs. H, we found a different metabolite
      distribution, with inosine, cytosine, creatine, and lactate being higher in S
      than in H brains, while the branched chain amino acids (leucine, isoleucine, and
      valine), phenylalanine, uracil, tyrosine, gamma-amino butyric acid, total
      aspartate (aspartate + N-acetyl aspartate) being lower in S. By a soft
      independent modelling of class analogy approach, 1 out of 3 A samples was
      assigned to class H. Furthermore, A brains were found to be higher in choline and
      choline-containing compounds. By means of partial least squares regression, an
      excellent correlation was found between the PrP(Sc) amount and the (1)H NMR
      metabolite profile of infected (S and A) sheep, and the metabolite mostly
      correlated with PrP(Sc) was alanine. The overall results, obtained using
      different chemometric tools, were able to describe a brain metabolite profile of
      infected sheep with and without clinical signs, compared to healthy ones, and
      indicated alanine as a biomarker for PrP(Sc) amounts in scrapie brains. 

PMID- 25959288
TI  - Environmental tobacco exposure is associated with vaccine modified measles in
      junior high school students.
AB  - Vaccine modified measles (VMM) affects individuals with attenuated vaccine
      induced immunity. An outbreak of measles occurred in a junior high school,
      starting from an unvaccinated eighth-grade student who developed natural measles
      and affected a majority of students who were immunized with a low potent strain
      of measles vaccine (TD97). To determine whether environmental tobacco smoke (ETS)
      exposure was associated with the development of VMM in this population, a
      questionnaire was used asking whether students had VMM symptoms during the
      outbreak and the smoking status of family members. VMM was defined in the study
      population as occurrence of fever and/or erythema, along with documented history
      of measles vaccination. A total of 513 students (85.9%) responded. Overall, the
      presence of in-house smokers did not differ between VMM students (49.3%) and non
      VMM students (50.2%). However, in the ninth grade, presence of an in-house smoker
      was significantly higher in the family of VMM students (54.0%) than in non-VMM
      students (36.6%) (P = 0.044). Urinary cotinine levels were also measured in
      selected students (n = 37). Among families with at least one smoker, urinary
      cotinine levels were significantly higher in VMM students than in non-VMM
      students (P = 0.032). Furthermore, a multivariable logistic regression analysis
      showed that a high urinary cotinine level (>10 ng/mg creatinine; 13.5 percentile)
      was associated with the development of VMM. Our findings suggest that a high
      level of ETS exposure may be associated with an increased risk of VMM in a
      population with attenuated vaccine induced immunity against measles.

PMID- 25959290
TI  - [Learning concepts of diagnosis in family medicine: the "mark robinson sign" -
      the traces that should not be there].
AB  - We review the mechanisms of the mental operation to identify the disease in
      family medicine, using five cases where the diagnosis process began in "the trace
      that should not be there" or "Robinson sign" as happened to Robinson Crusoe when
      he saw a human footprint on the beach of the "desert island". How could it be
      there?; It was a mystery, and based on metaphors, we framed the mechanism of "the
      trace that should not be there" mainly in the first phase of clinical or
      intuitive reasoning, but this intuition of the doctor should be accompanied by
      the diagnostic process, like the "basso continuo" of Baroque music, allowing
      improvisation and personal style, and in this way, eventually observing the
      footprint "that should not have been there" that may arise in the analytical, as
      well as in the verification phase of the assumptions made. 

PMID- 25959289
TI  - In vivo wound-healing effects of novel benzalkonium chloride-loaded hydrocolloid
      wound dressing.
AB  - The purpose of this study was to evaluate the wound-healing effects of a novel
      benzalkonium chloride (BC)-loaded hydrocolloid wound dressing (HCD). A BC-loaded
      HCD was prepared with various constituents using a hot melting method, and its
      mechanical properties and antimicrobial activities were assessed. The in vivo
      wound healings of the BC-loaded HCD in various would models were evaluated in
      rats compared with a commercial wound dressing, DuodermTM. This BC-loaded HCD
      gave better skin adhesion, swelling, mechanical strength, and flexibility
      compared with the commercial wound dressing. It showed excellent antimicrobial
      activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas
      aeruginosa. In addition, as compared with the commercial wound dressing, it
      showed more improved wound healings and tissue restoration effect on the
      excision, infection, and abrasion wounds in rats. Thus, this novel BC-loaded HCD
      would be an excellent alternative to the commercial wound dressing for treatment
      of various wounds.

PMID- 25959291
TI  - [Gaps in diagnosis and nutritional counseling of children aged 1 to 5 years in
      family medicine clinics in Mexico: Analysis of the electronic health records].

PMID- 25959292
TI  - Investigation of exotic stable calcium carbides using theory and experiment.
AB  - It is well known that pressure causes profound changes in the properties of atoms
      and chemical bonding, leading to the formation of many unusual materials. Here we
      systematically explore all stable calcium carbides at pressures from ambient to
      100 GPa using variable-composition evolutionary structure predictions using the
      USPEX code. We find that Ca5C2, Ca2C, Ca3C2, CaC, Ca2C3 and CaC2 have stability
      fields on the phase diagram. Among these, Ca2C and Ca2C3 are successfully
      synthesized for the first time via high-pressure experiments with excellent
      structural correspondence to theoretical predictions. Of particular significance
      is the base-centred monoclinic phase (space group C2/m) of Ca2C, a quasi-two
      dimensional metal with layers of negatively charged calcium atoms, and the
      primitive monoclinic phase (space group P21/c) of CaC with zigzag C4 groups.
      Interestingly, strong interstitial charge localization is found in the structure
      of R-3m-Ca5C2 with semi-metallic behaviour. 

PMID- 25959293
TI  - Expression of ectonucleotidases in the prosencephalon of melatonin-proficient C3H
      and melatonin-deficient C57Bl mice: spatial distribution and time-dependent
      changes.
AB  - Extracellular purines (ATP, ADP, AMP and adenosine) are important signaling
      molecules in the CNS. Levels of extracellular purines are regulated by enzymes
      located at the cell surface referred to as ectonucleotidases. Time-dependent
      changes in their expression could profoundly influence the availability of
      extracellular purines and thereby purinergic signaling. Using radioactive in situ
      hybridization, we analyzed the mRNA distribution of the enzymes NTPDase1, -2 and 
      3 and ecto-5'-nucleotidase in the prosencephalon of two mouse strains: melatonin
      proficient C3H and melatonin-deficient C57Bl. The mRNAs of these enzymes were
      localized to specific brain regions, such as hippocampus, striatum, medial
      habenula and ventromedial hypothalamus. NTPDase3 expression was more widely
      distributed than previously thought. All ectonucleotidases investigated revealed
      a prominent time-dependent expression pattern. In C3H, the mRNA expression of all
      four enzymes gradually increased during the day and peaked during the night. In
      contrast, in C57Bl, ecto-5'-nucleotidase expression peaked at the beginning of
      the day and gradually decreased to trough levels at night. Recording of locomotor
      activity revealed higher daytime activity of C57Bl than of C3H. Our results
      indicate that the expression of ectonucleotidases varies according to time and
      genotype and suggest that melatonin exerts modulatory effects associated with
      different regulations of purinergic signaling in the brain. These findings
      provide an important basis for further examination of the complexity of the
      purinergic system in the brain. 

PMID- 25959294
TI  - Current concepts of hair cell differentiation and planar cell polarity in inner
      ear sensory organs.
AB  - Phylogenetically and ontogenetically, vertebrate development led to the
      generation of several inner ear sensory organs. During embryogenesis, cell fate
      specification determines whether each progenitor cell differentiates into a
      sensory hair cell or a supporting cell within the common sensory primordium.
      Finally, all sensory epithelia of the inner ear consist of a hair cell/supporting
      cell mosaic, albeit with anatomical differences depending on the sensory organ
      type. Hair cells develop a polarized bundle of stereovilli that is of functional
      importance for mechanotransduction. After initiating stereovillar development,
      hair cells align their bundles in a coordinated fashion, generating a
      characteristic hair cell orientation pattern, a process referred to as planar
      cell polarity (PCP). The pathway that controls PCP in the inner ear needs both to
      establish the development of a polarized morphology of the stereovillar bundle of
      the hair cell and to organize a systematic hair cell alignment. Because the hair
      cell orientation patterns of the various inner ear organs and vertebrate species
      differ fundamentally, it becomes apparent that in vertebrates, different aspects
      of PCP need to be independently controlled. In spite of important progress
      recently gained in the field of PCP research, we still need to identify the
      mechanisms (1) that initiate molecular asymmetries in cells, (2) that guide the
      transmission of polarity information from cell to cell, and (3) that consistently
      translate such polarity information into morphological asymmetries of hair cells.

PMID- 25959295
TI  - Central Nervous System Demyelination and Remyelination is Independent from
      Systemic Cholesterol Level in Theiler's Murine Encephalomyelitis.
AB  - High dietary fat and/or cholesterol intake is a risk factor for multiple diseases
      and has been debated for multiple sclerosis. However, cholesterol biosynthesis is
      a key pathway during myelination and disturbances are described in demyelinating
      diseases. To address the possible interaction of dyslipidemia and demyelination,
      cholesterol biosynthesis gene expression, composition of the body's major lipid
      repositories and Paigen diet-induced, systemic hypercholesterolemia were examined
      in Theiler's murine encephalomyelitis (TME) using histology,
      immunohistochemistry, serum clinical chemistry, microarrays and high-performance
      thin layer chromatography. TME-virus (TMEV)-infected mice showed progressive loss
      of motor performance and demyelinating leukomyelitis. Gene expression associated
      with cholesterol biosynthesis was overall down-regulated in the spinal cord of
      TMEV-infected animals. Spinal cord levels of galactocerebroside and sphingomyelin
      were reduced on day 196 post TMEV infection. Paigen diet induced serum
      hypercholesterolemia and hepatic lipidosis. However, high dietary fat and
      cholesterol intake led to no significant differences in clinical course,
      inflammatory response, astrocytosis, and the amount of demyelination and
      remyelination in the spinal cord of TMEV-infected animals. The results suggest
      that down-regulation of cholesterol biosynthesis is a transcriptional marker for
      demyelination, quantitative loss of myelin-specific lipids, but not cholesterol
      occurs late in chronic demyelination, and serum hypercholesterolemia exhibited no
      significant effect on TMEV infection. 

PMID- 25959296
TI  - Identification of differentially expressed genes related to aphid resistance in
      cucumber (Cucumis sativus L.).
AB  - Cucumber, a very important vegetable crop worldwide, is easily damaged by pests.
      Aphids (Aphis gossypii Glover) are among the most serious pests in cucumber
      production and often cause severe loss of yield and make fruit quality get worse.
      Identifying genes that render cucumbers resistant to aphid-induced damage and
      breeding aphid-resistant cucumber varieties have become the most promising
      control strategies. In this study, a Illumina Genome Analyzer platform was
      applied to monitor changes in gene expression in the whole genome of the cucumber
      cultivar 'EP6392' which is resistant to aphids. Nine DGE libraries were
      constructed from infected and uninfected leaves. In total, 49 differentially
      expressed genes related to cucumber aphid resistance were screened during the
      treatment period. These genes are mainly associated with signal transduction,
      plant-pathogen interactions, flavonoid biosynthesis, amino acid metabolism and
      sugar metabolism pathways. Eight of the 49 genes may be associated with aphid
      resistance. Finally, expression of 9 randomly selected genes was evaluated by qRT
      PCR to verify the results for the tag-mapped genes. With the exception of 1
      aminocyclopropane-1-carboxylate oxidase homolog 6, the expression of the chosen
      genes was in agreement with the results of the tag-sequencing analysis patterns. 

PMID- 25959297
TI  - Stable intergenerational associations of childhood overweight during the
      development of the obesity epidemic.
AB  - OBJECTIVE: The obesity epidemic may have developed as a response to the
      obesogenic environment among the genetically predisposed. This investigation
      examined whether the intergenerational resemblances in childhood overweight
      changed across the development of the obesity epidemic in groups of children born
      to parents with and without childhood overweight. METHODS: The study population
      was from the Copenhagen School Health Records Register, which includes age- and
      sex-specific body mass index (BMI; kg/m(2) ) of children. This study used BMI
      values from 7-year-old children born 1952-1989 and from their parents at ages 7
      and 13 years. The available number of parent-child pairs ranged from 17,926
      through 42,184. The odds ratios of childhood overweight (BMI z-score >90th
      percentile) were calculated using logistic regression by parental BMI groups (BMI
      > or <=90th percentile) and child birth year intervals. RESULTS: Stable levels in
      parent-child overweight associations were observed across child BMI groups born
      to parents with and without childhood overweight. A slight upward odds ratio
      trend was observed across time in children born to two overweight parents at age
      13, but not at age 7 years. CONCLUSIONS: Parent-child resemblance in childhood
      overweight showed small changes during the development of the obesity epidemic,
      suggesting that the obesogenic environment inducing the epidemic in Denmark
      influenced children irrespective of their familial predisposition.

PMID- 25959298
TI  - Validating a tool to measure auxiliary nurse midwife and nurse motivation in
      rural Nepal.
AB  - BACKGROUND: A global shortage of health workers in rural areas increases the
      salience of motivating and supporting existing health workers. Understandings of
      motivation may vary in different settings, and it is important to use measurement
      methods that are contextually appropriate. We identified a measurement tool,
      previously used in Kenya, and explored its validity and reliability to measure
      the motivation of auxiliary nurse midwives (ANM) and staff nurses (SN) in rural
      Nepal. METHOD: Qualitative and quantitative methods were used to assess the
      content validity, the construct validity, the internal consistency and the
      reliability of the tool. We translated the tool into Nepali and it was
      administered to 137 ANMs and SNs in three districts. We collected qualitative
      data from 78 nursing personnel and district- and central-level stakeholders using
      interviews and focus group discussions. We calculated motivation scores for ANMs
      and SNs using the quantitative data and conducted statistical tests for validity
      and reliability. Motivation scores were compared with qualitative data.
      Descriptive exploratory analysis compared mean motivation scores by ANM and SN
      sociodemographic characteristics. RESULTS: The concept of self-efficacy was added
      to the tool before data collection. Motivation was revealed through
      conscientiousness. Teamwork and the exertion of extra effort were not adequately
      captured by the tool, but important in illustrating motivation. The statement on
      punctuality was problematic in quantitative analysis, and attendance was more
      expressive of motivation. The calculated motivation scores usually reflected ANM
      and SN interview data, with some variation in other stakeholder responses. The
      tool scored within acceptable limits in validity and reliability testing and was
      able to distinguish motivation of nursing personnel with different
      sociodemographic characteristics. CONCLUSIONS: We found that with minor
      modifications, the tool provided valid and internally consistent measures of
      motivation among ANMs and SNs in this context. We recommend the use of this tool
      in similar contexts, with the addition of statements about self-efficacy,
      teamwork and exertion of extra effort. Absenteeism should replace the punctuality
      statement, and statements should be worded both positively and negatively to
      mitigate positive response bias. Collection of qualitative data on motivation
      creates a more nuanced understanding of quantitative scores.

PMID- 25959299
TI  - Impaired face detection may explain some but not all cases of developmental
      prosopagnosia.
AB  - Developmental prosopagnosia (DP) is defined by severe face recognition
      difficulties due to the failure to develop the visual mechanisms for processing
      faces. The two-process theory of face recognition (Morton & Johnson, 1991)
      implies that DP could result from a failure of an innate face detection system;
      this failure could prevent an individual from then tuning higher-level processes
      for face recognition (Johnson, 2005). Work with adults indicates that some
      individuals with DP have normal face detection whereas others are impaired.
      However, face detection has not been addressed in children with DP, even though
      their results may be especially informative because they have had less
      opportunity to develop strategies that could mask detection deficits. We tested
      the face detection abilities of seven children with DP. Four were impaired at
      face detection to some degree (i.e. abnormally slow, or failed to find faces)
      while the remaining three children had normal face detection. Hence, the cases
      with impaired detection are consistent with the two-process account suggesting
      that DP could result from a failure of face detection. However, the cases with
      normal detection implicate a higher-level origin. The dissociation between normal
      face detection and impaired identity perception also indicates that these
      abilities depend on different neurocognitive processes. 

PMID- 25959300
TI  - Nonaqueous lyotropic ionic liquid crystals: preparation, characterization, and
      application in extraction.
AB  - A class of new ionic liquid (IL)-based nonaqueous lyotropic liquid crystals
      (LLCs) and the development of an efficient IL extraction process based on LC
      chemistry are reported. The nonaqueous LLCs feature extraordinarily high
      extraction capacity, excellent separation selectivity, easy recovery, and
      biocompatibility. This work also demonstrates that the introduction of self
      assembled anisotropic nanostructures into an IL system is an efficient way to
      overcome the intrinsically strong polarity of ILs and enhances the molecular
      recognition ability of ILs. The distribution coefficients of IL-based LLCs for
      organic compounds with H-bond donors reached unprecedented values of 50-60 at
      very high feed concentrations (>100 mg mL(-1) ), which are 800-1000 times greater
      than those of common ILs as well as traditional organic and polymer extractants.
      The IL-based nonaqueous LLCs combining the unique properties of ILs and LCs open
      a new avenue for the development of high-performance extraction methods. 

PMID- 25959301
TI  - Dietary mobile apps and their effect on nutritional indicators in chronic renal
      disease: A systematic review.
AB  - Dietary apps for mobile technology are becoming increasingly available and can
      assist in recording food and fluid intake for nutrition assessment or monitoring.
      Patients with chronic renal disease, particularly those on dialysis, are required
      to make significant dietary changes. This study systematically reviews the
      current literature to assess whether dietary mobile apps improve dietary intake
      and clinical outcomes in the renal population, specifically those with chronic
      kidney disease levels 3-5, including dialysis. A systematic search of Medline
      Complete, CINAHL, Embase, PsycINFO and the Cochrane Library was performed and
      supplemented by manual searches of citation and reference lists. Of the 712
      studies considered, five were eligible for inclusion in this review. The quality
      of each included study was assessed using a Quality Criteria Checklist for
      Primary Research. Among five studies (two randomised controlled trials (RCTs) and
      three case studies/reports), none found significant changes in nutrient intake,
      biochemical markers or intradialytic weight gain, through the use of dietary
      mobile apps. The included studies show potential for clinical benefits of mobile
      app interventions in a renal population. However, there is a need for additional
      rigorous trials to demonstrate if there is a clinical benefit of mobile app
      interventions in this population.

PMID- 25959302
TI  - Switch From a Long-term to a Short-term Ventricular Assist Device as a Bridge to
      Heart Transplantation.

PMID- 25959303
TI  - Organization of Heart Failure Care in Spain: Characteristics of Heart Failure
      Units.

PMID- 25959304
TI  - Reply to: "Strain ultrasound elastography for liver diseases".

PMID- 25959305
TI  - Determination of gas flow through airway exchange catheters: measured and
      calculated values and dependence on pressure and entrainment.
AB  - Serious complications have been described during oxygenation of patients with
      airway exchange catheters, due to catheter malpositioning, accidentally applied
      high airway pressures or high delivered volumes. In this in-vitro study, we
      analysed gas flow through various airway exchange catheters and described its
      dependence on driving pressure and entrainment. We applied driving pressures
      between 0.5 and 2.5 bar and observed maximal flow rates of 3.6 l.s(-1) . Measured
      gas flow values differed significantly from values calculated according to the
      Hagen-Poiseuille equation. Although flow restriction in ventilators and small
      bore connectors will limit gas flow, large gas volumes may be unintentionally
      applied via the airway exchange catheters, leading to serious complications. 

PMID- 25959306
TI  - Comparison of the Avalon Dual-Lumen Cannula with Conventional Cannulation
      Technique for Venovenous Extracorporeal Membrane Oxygenation.
AB  - BACKGROUND: Comparison of two kinds of cannulation (double-lumen cannula [DLC,
      Avalon Elite Bicaval Dual Lumen Catheter] and conventional cannulation with two
      cannulas) for venovenous extracorporeal membrane oxygenation (ECMO) therapy in
      terms of effectiveness, usage complexity, and costs. METHODS: Retrospective case
      series of 17 patients who received venovenous ECMO therapy due to acute
      respiratory distress syndrome (ARDS) between January 2010 and March 2012. Nine
      patients were treated with the DLC and eight patients with conventional
      cannulation. We analyzed the outcome data, ECMO values, respirator settings,
      blood gas values, realized prone positioning, and costs, and compared both
      methods. RESULTS: Both kinds of cannulation are efficient regarding oxygenation
      and decarboxylation. There is no significant difference in mortality,
      hospitalization time (intensive care unit [ICU] and hospital) and complications
      during ECMO therapy between both groups. Cannula implantation is much more
      complex in the DLC group and requires more experience in TEE (transesophageal
      echocardiography) diagnostics and cannulation technique. In addition, the costs
      for the Avalon (MAQUET Cardiopulmonary AG, Germany) cannula are significantly
      higher than for conventional cannulation. Furthermore, prone positioning could be
      easier achieved in the DLC group. CONCLUSION: In summary, double-lumen
      cannulation allows sufficient gas exchange with more effort (material, technical,
      and physicians' experience) and higher costs but better mobilization
      possibilities (particularly prone position) and potential avoidance of deep
      sedation and mechanical ventilation. From the current point of view, the DLC
      should be reserved for special cases.

PMID- 25959307
TI  - Impact of Metabolic Syndrome on Subclinical Atherosclerosis in Asymptomatic
      Individuals.
AB  - BACKGROUND: Little is known about subclinical atherosclerosis on coronary
      computed tomographic angiography (CCTA) in asymptomatic individuals with
      metabolic syndrome (MetS). METHODS AND RESULTS: We analyzed 5,213 asymptomatic
      individuals who underwent CCTA. A cardiac event was defined as a composite of all
      cause death, myocardial infarction, unstable angina, or coronary
      revascularization. Of the study participants, 2,042 (39.2%) had MetS. MetS was an
      independent predictor of significant coronary artery disease (CAD) in at least 1
      coronary artery (odds ratio [OR]=1.992, 95% confidence interval [CI]=1.623-2.445,
      P<0.001) and significant CAD in the left main (LM) or proximal left anterior
      descending (LAD) artery (OR=2.151, 95% CI=1.523-3.037, P<0.001). During the
      follow-up period (median 28.1 [interquartile range, 19.2-36.5] months), 111
      individuals had 114 cardiac events. Individuals with MetS were significantly
      associated with more cardiac events than those without (RR [rate ratio]=1.67, 95%
      CI=1.15-2.43, P=0.007). In the MetS group, individuals with significant CAD had
      the majority of cardiac events (RR=64.33, 95% CI=29.17-141.88, P<0.001).
      Furthermore, in the MetS with significant CAD group, those with significant CAD
      in the LM or proximal LAD had more cardiac events (RR=2.63, 95% CI=1.51-4.59,
      P=0.001). CONCLUSIONS: MetS was associated with subclinical atherosclerosis on
      CCTA with subsequent high risk for cardiac events. These findings suggest the
      importance of reducing unfavorable metabolic conditions in asymptomatic
      individuals.

PMID- 25959308
TI  - Selective enrichment of STRs for applications in forensic human identification.
AB  - Forensic human identification (HID) is currently based on determining repeat
      length polymorphisms located in short tandem repeat regions in the human genome.
      Despite the great progress made in the area of multiplex PCR-based approaches,
      limitations associated with challenging forensic samples such as DNA degradation,
      cooccurrence of inhabited microbial DNA and PCR inhibitors significantly affect
      the success rate of human DNA profiling. We have developed a sequence-specific
      pre-PCR STR enrichment method and evaluated its efficacy using DNA samples doped
      with various contaminants in view of its application on compromised forensic
      samples. This strategy has enabled us to generate complete and reproducible DNA
      profiles from samples doped with fivefold excess of nonhuman DNA and three to
      fourfold excess of various potent PCR inhibitors than that is claimed to be
      tolerated by some of the widely used commercial multiplex STR kits, from as
      little as two nanograms of degraded human DNA. The "hybrid capture"-based STR
      enrichment strategy described in this study is easily adaptable and offers a
      sensitive, efficient, and economical approach for successful human DNA profiling
      from compromised and recalcitrant forensic samples that are usually encountered
      in mass disaster incidents and missing persons' identifications. 

PMID- 25959310
TI  - Structural positioning of nurse leaders and empowerment.
AB  - AIMS AND OBJECTIVES: To analyse the reporting structures of nursing leaders of
      publicly funded hospitals and seek both the views of nurse leaders and Chief
      Executive Officers/Chief Operating Officers on the structural positioning of
      nurse leaders in the organisation. BACKGROUND: Concern that the continuing
      restructuring within hospital structures and focus on economic outputs in health
      services is diminishing the value of nursing leadership. DESIGN: Qualitative
      surveys with Nursing leaders and Chief Executive Officers of public hospitals.
      METHODS: Seventeen Directors of Nursing and 10 Chief Executive Officer/Chief
      Operating Officers' responses were received using two semi-structured
      questionnaires. Themes were developed from data coded and analysed by hand.
      RESULTS: Four broad themes emerged from analysis of the data: (1) variable
      positional reporting between Director of Nursing and Chief Executive Officers
      occurred; (2) variable levels of inclusion and influence at the executive
      decision-making level; (3) ambiguous financial responsibilities and
      accountabilities held by Director of Nursing; and (4) blurred lines existed
      between operational and professional reporting lines. Findings unique to the
      research indicate that the varying levels of visibility and inclusion impact on
      the structural positioning of nurse leaders which influences authority and
      empowerment. CONCLUSION: Responses from the data analysis indicate that the
      structural power of nurse leaders defined by the factors of opportunity, power
      and proportion were hindered by dual accountability reporting lines and a lack of
      financial control. RELEVANCE TO CLINICAL PRACTICE: The structural positioning of
      nurse leaders is vital to ensure that they are empowered and able to meet the
      adaptations required in a changing environment that supports the delivery of
      effective, quality healthcare.

PMID- 25959309
TI  - Degradation of Ndd1 by APC/C(Cdh1) generates a feed forward loop that times
      mitotic protein accumulation.
AB  - Ndd1 activates the Mcm1-Fkh2 transcription factor to transcribe mitotic
      regulators. The anaphase-promoting complex/cyclosome activated by Cdh1
      (APC/C(Cdh1)) mediates the degradation of proteins throughout G1. Here we show
      that the APC/C(Cdh1) ubiquitinates Ndd1 and mediates its degradation, and that
      APC/C(Cdh1) activity suppresses accumulation of Ndd1 targets. We confirm putative
      Ndd1 targets and identify novel ones, many of them APC/C(Cdh1) substrates. The
      APC/C(Cdh1) thus regulates these proteins in a dual manner-both
      pretranscriptionally and post-translationally, forming a multi-layered
      feedforward loop (FFL). We predict by mathematical modelling and verify
      experimentally that this FFL introduces a lag between APC/C(Cdh1) inactivation at
      the end of G1 and accumulation of genes transcribed by Ndd1 in G2. This
      regulation generates two classes of APC/C(Cdh1) substrates, early ones that
      accumulate in S and late ones that accumulate in G2. Our results show how the
      dual state APC/C(Cdh1) activity is converted into multiple outputs by
      interactions between its substrates.

PMID- 25959311
TI  - JAK2 46/1 haplotype is associated with JAK2 V617F--positive myeloproliferative
      neoplasms in Brazilian patients.
AB  - INTRODUCTION: This study aimed to verify the association between the JAK2 46/1
      haplotype (V617F positive) and some hematological parameters in BCR-ABL-negative
      chronic myeloproliferative neoplasms (cMPNs) in our population. METHODS: The
      blood samples obtained from the patients with cMPN were genotyped for the JAK2
      V617F mutation and JAK2 rs10974944 SNP screening using a PCR-RFLP assay. RESULTS:
      The JAK2 V617F mutation was detected in 80.15% of patients. The G variant of
      rs10974944 was more frequent in all MPNs, especially those that were JAK2 V617F
      positive, than in the control population. We also compared the 46/1 haplotype
      status in each MPN disease entity, polycythemia vera (PV), essential
      thrombocythemia (ET), primary myelofibrosis (PMF), and MPNu with controls. The G
      allele frequency relative to controls was significantly enriched in patients with
      PV and ET, but not in those with PMF and MPNu. PV and ET patients especially, all
      of whom had the JAK2 V617F mutation, showed significant excess of the G allele.
      The frequency of JAK2 V617F mutation was associated with elevated hematological
      parameters, but when we analyze the occurrence of the mutation and the presence
      of the G allele, just the high hemoglobin was significantly. CONCLUSION: In
      agreement with previous reports, JAK2 46/1 haplotype for JAK2 V617F was
      associated with cMPN positive in Brazilian patients.

PMID- 25959312
TI  - New technical design of food packaging makes the opening process easier for
      patients with hand disorders.
AB  - Opening packaged food is a complex daily activity carried out worldwide. Peelable
      packaging, as used for cheese or meat, causes real problems for many consumers,
      especially elderly people and those with hand disorders. Our aim was to
      investigate the possibility of producing meat packaging that is easier for
      patients with hand disorders to open. One hundred patients with hand
      osteoarthritis were asked to open a meat package currently available in
      supermarkets (Type A) and a modified, newly designed version (Type B), and rate
      their experiences with a consumer satisfaction index (CSI). The mean CSI of the
      Type B packs was 68.9%, compared with 41.9% for Type A (p < 0.0001). These
      results show that manufacturers today can produce easy-to-open food packages that
      afford greater consumer satisfaction. Such future packaging would benefit not
      only people with hand disorders but also the population as a whole. 

PMID- 25959313
TI  - Practicing universal design to actual hand tool design process.
AB  - UD evaluation principles are difficult to implement in product design. This study
      proposes a methodology for implementing UD in the design process through user
      participation. The original UD principles and user experience are used to develop
      the evaluation items. Difference of product types was considered. Factor analysis
      and Quantification theory type I were used to eliminate considered inappropriate
      evaluation items and to examine the relationship between evaluation items and
      product design factors. Product design specifications were established for
      verification. The results showed that converting user evaluation into crucial
      design verification factors by the generalized evaluation scale based on product
      attributes as well as the design factors applications in product design can
      improve users' UD evaluation. The design process of this study is expected to
      contribute to user-centered UD application. 

PMID- 25959314
TI  - Complex socio-technical systems: Characterization and management guidelines.
AB  - Although ergonomics has paid increasing attention to the perspective of
      complexity, methods for its operationalization are scarce. This study introduces
      a framework for the operationalization of the "attribute view" of complexity,
      which involves: (i) the delimitation of the socio-technical system (STS); (ii)
      the description of four complexity attributes, namely a large number of elements
      in dynamic interactions, a wide diversity of elements, unexpected variability,
      and resilience; (iii) the assessment of six management guidelines, namely design
      slack, give visibility to processes and outcomes, anticipate and monitor the
      impacts of small changes, monitor the gap between prescription and practice,
      encourage diversity of perspectives when making decisions, and create an
      environment that supports resilience; and (iv) the identification of leverage
      points for improving the STS design, based on both the analysis of relationships
      among the attributes and their classification as irreducible/manageable
      complexity, and liability/asset. The use of the framework is illustrated by the
      study of an emergency department of a University hospital. Data collection
      involved analysis of documents, observations of work at the front-line,
      interviews with employees, and the application of questionnaires. 

PMID- 25959315
TI  - Designers' and users' roles in participatory design: What is actually co-designed
      by participants?
AB  - This research deals with an analysis of forms of participation in a participatory
      design (PD) process of a software that assesses the sustainability of
      agricultural cropping systems. We explore the actual forms of participation of
      designers and users by adapting an Actual Role Analysis in Design approach
      (Barcellini et al., 2013) to capture the levels of abstraction (conceptual,
      functional and operational) of participants' discussions. We show that: (1) the
      process does not only concern the design of the artifact itself, but also the
      design of the concept of sustainability; (2) all participants (users & designers)
      have a role in co-designing the concept (in our case, sustainability); (3) some
      roles and profiles are key to this co-design. We discuss our contributions to
      both the research and the practices of participatory design. These contributions
      deal with the production of a method and related knowledge about actual
      activities in participatory design situations. They may support the development
      of relevant training programs regarding participatory situations, or be reflexive
      activities that can help those who are involved in designing and leading in
      participatory situations, to make improvements. 

PMID- 25959316
TI  - Sonification of in-vehicle interface reduces gaze movements under dual-task
      condition.
AB  - In-car infotainment systems (ICIS) often degrade driving performances since they
      divert the driver's gaze from the driving scene. Sonification of hierarchical
      menus (such as those found in most ICIS) is examined in this paper as one
      possible solution to reduce gaze movements towards the visual display. In a dual
      task experiment in the laboratory, 46 participants were requested to prioritize a
      primary task (a continuous target detection task) and to simultaneously navigate
      in a realistic mock-up of an ICIS, either sonified or not. Results indicated that
      sonification significantly increased the time spent looking at the primary task,
      and significantly decreased the number and the duration of gaze saccades towards
      the ICIS. In other words, the sonified ICIS could be used nearly exclusively by
      ear. On the other hand, the reaction times in the primary task were increased in
      both silent and sonified conditions. This study suggests that sonification of
      secondary tasks while driving could improve the driver's visual attention of the
      driving scene. 

PMID- 25959317
TI  - Anthropometry of external auditory canal by non-contactable measurement.
AB  - Human ear canals cannot be measured directly with existing general measurement
      tools. Furthermore, general non-contact optical methods can only conduct simple
      peripheral measurements of the auricle and cannot obtain the internal ear canal
      shape-related measurement data. Therefore, this study uses the computed
      tomography (CT) technology to measure the geometric shape of the ear canal and
      the shape of the ear canal using a non-invasive method, and to complete the
      anthropometry of external auditory canal. The results of the study show that the
      average height and width of ear canal openings, and the average depth of the
      first bend for men are generally longer, wider and deeper than those for women.
      In addition, the difference between the height and width of the ear canal opening
      is about 40% (p < 0.05). Hence, the circular cross-section shape of the earplugs
      should be replaced with an elliptical cross-section shape during manufacturing
      for better fitting. 

PMID- 25959318
TI  - Lumbar compression forces while lifting and carrying with two and four workers.
AB  - Team lifting and carrying is advised when loads exceed 25 kg and mechanical
      lifting is not feasible. The aim of this study was to assess mean, maximum and
      variability of peak lumbar compression forces which occur daily at construction
      sites. Therefore, 12 ironworkers performed 50-kg two-worker and 100-kg four
      worker lifting and carrying tasks in a laboratory experiment. The 50-kg two
      worker lifts resulted in significantly higher mean (Delta 537 N) and maximum
      (Delta 586 N) peak lumbar compression forces compared with the 100-kg four-worker
      lifts. The lowest mean and maximum peak lumbar compression forces were found
      while carrying on level ground and increased significantly when stepping over
      obstacles and up platforms. Lifting 100 kg with four workers in a rectangular
      line up resulted in lower compression forces compared with lifting 50 kg with two
      workers standing next to each other. When loads are carried manually routes
      should be free of any obstacles to be overcome.

PMID- 25959319
TI  - The influence of occupation and age on maximal and rapid lower extremity
      strength.
AB  - The aims of this study were to 1) examine the influence of age and occupation on
      maximal and rapid strength of the lower-extremity muscles and 2) examine the
      relationship between maximal and rapid strength and physical workload (work index
      (WI)) in the blue-collar (BC) cohort. Peak torque (PT) and peak rate of torque
      development (peakRTD) of the leg extensors (LE), leg flexors (LF), and plantar
      flexors (PF) were assessed in 47 young (age = 24.1 +/- 2.4 years) and 41 middle
      aged (52.4 +/- 5.2 years) white-collar (WC) and BC men. Middle-aged workers
      exhibited lower PT for all muscles, and peakRTD for the LF and PF muscles. A
      positive relationship (r = 0.59; P < 0.01) was observed between WI and peakRTD
      for the PF in the young BC workers, however, this relationship was negative (r = 
      0.45; P = 0.053) for the LF of the middle-aged BC workers. Lowering physical work
      demands and/or incorporating effective health-related practices for employees may
      be appealing strategies to enhance aging workers' productivity and longevity in
      the workforce. 

PMID- 25959320
TI  - Adaptive neuro-fuzzy inference systems with k-fold cross-validation for energy
      expenditure predictions based on heart rate.
AB  - This paper presents a new model based on adaptive neuro-fuzzy inference systems
      (ANFIS) to predict oxygen consumption (VO2) from easily measured variables. The
      ANFIS prediction model consists of three ANFIS modules for estimating the Flex-HR
      parameters. Each module was developed based on clustering a training set of data
      samples relevant to that module and then the ANFIS prediction model was tested
      against a validation data set. Fifty-eight participants performed the Meyer and
      Flenghi step-test, during which heart rate (HR) and VO2 were measured. Results
      indicated no significant difference between observed and estimated Flex-HR
      parameters and between measured and estimated VO2 in the overall HR range, and
      separately in different HR ranges. The ANFIS prediction model (MAE = 3 ml kg(-1)
      min(-1)) demonstrated better performance than Rennie et al.'s (MAE = 7 ml kg(-1)
      min(-1)) and Keytel et al.'s (MAE = 6 ml kg(-1) min(-1)) models, and comparable
      performance with the standard Flex-HR method (MAE = 2.3 ml kg(-1) min(-1))
      throughout the HR range. The ANFIS model thus provides practitioners with a
      practical, cost- and time-efficient method for VO2 estimation without the need
      for individual calibration.

PMID- 25959321
TI  - An experiment with content distribution methods in touchscreen mobile devices.
AB  - This paper compares the usability of three different content distribution methods
      (scrolling, paging and internal links) in touchscreen mobile devices as means to
      display web documents. Usability is operationalized in terms of effectiveness,
      efficiency and user satisfaction. These dimensions are then measured in an
      experiment (N = 23) in which users are required to find words in regular-length
      web documents. Results suggest that scrolling is statistically better in terms of
      efficiency and user satisfaction. It is also found to be more effective but
      results were not significant. Our findings are also compared with existing
      literature to propose the following guideline: "try to use vertical scrolling in
      web pages for mobile devices instead of paging or internal links, except when the
      content is too large, then paging is recommended". With an ever increasing number
      of touchscreen web-enabled mobile devices, this new guideline can be relevant for
      content developers targeting the mobile web as well as institutions trying to
      improve the usability of their content for mobile platforms. 

PMID- 25959322
TI  - Evaluating the physical demands when using sled-type stair descent devices to
      evacuate mobility-limited occupants from high-rise buildings.
AB  - The physical demands on evacuators were investigated when using different types
      of sled-type stair descent devices designed for the emergency evacuation of high
      rise buildings. Twelve firefighters used six sled-type stair descent devices
      during simulated evacuations. The devices were evaluated under two staircase
      width conditions (1.12, and 1.32 m). Dependent measures included
      electromyographic (EMG) data, heart rates, Borg Scale ratings, and descent
      velocities. All stair descent speeds were below those reported during pedestrian
      egress trials. With the exception of the inflatable device, the devices operated
      by two evacuators had higher descent speeds than those operated by a single
      evacuator. High friction materials under the sleds facilitated control and
      reduced the muscle demands on stairs but increased physical demands on the
      landings. Usability assessments found devices with shorter overall lengths had
      fewer wall contacts on the landing, and handles integrated in the straps were
      preferred by the evacuators. 

PMID- 25959323
TI  - Mobile input device type, texting style and screen size influence upper extremity
      and trapezius muscle activity, and cervical posture while texting.
AB  - This study aimed to determine the effects of input device type, texting style,
      and screen size on upper extremity and trapezius muscle activity and cervical
      posture during a short texting task in college students. Users of a physical
      keypad produced greater thumb, finger flexor, and wrist extensor muscle activity
      than when texting with a touch screen device of similar dimensions. Texting on
      either device produced greater wrist extensor muscle activity when texting with 1
      hand/thumb compared with both hands/thumbs. As touch screen size increased, more
      participants held the device on their lap, and chose to use both thumbs less.
      There was also a trend for greater finger flexor, wrist extensor, and trapezius
      muscle activity as touch screen size increased, and for greater cervical flexion,
      although mean differences for cervical flexion were small. Future research can
      help inform whether the ergonomic stressors observed during texting are
      associated with musculoskeletal disorder risk. 

PMID- 25959324
TI  - Use of adaptive cruise control functions on motorways and urban roads: Changes
      over time in an on-road study.
AB  - The study aimed at investigating how drivers use Adaptive Cruise Control and its
      functions in distinct road environments and to verify if changes occur over time.
      Fifteen participants were invited to drive a vehicle equipped with a Stop & Go
      Adaptive Cruise Control system on nine occasions. The course remained the same
      for each test run and included roads on urban and motorway environments. Results
      showed significant effect of experience for ACC usage percentage, and selection
      of the shortest time headway value in the urban road environment. This indicates
      that getting to know a system is not a homogenous process, as mastering the use
      of all the system's functions can take differing lengths of time in distinct road
      environments. Results can be used not only for the development of the new
      generation of systems that integrate ACC functionalities but also for determining
      the length of training required to operate an ACC system. 

PMID- 25959325
TI  - Human error identification for laparoscopic surgery: Development of a motion
      economy perspective.
AB  - This study postulates that traditional human error identification techniques fail
      to consider motion economy principles and, accordingly, their applicability in
      operating theatres may be limited. This study addresses this gap in the
      literature with a dual aim. First, it identifies the principles of motion economy
      that suit the operative environment and second, it develops a new error mode
      taxonomy for human error identification techniques which recognises motion
      economy deficiencies affecting the performance of surgeons and predisposing them
      to errors. A total of 30 principles of motion economy were developed and
      categorised into five areas. A hierarchical task analysis was used to break down
      main tasks of a urological laparoscopic surgery (hand-assisted laparoscopic
      nephrectomy) to their elements and the new taxonomy was used to identify errors
      and their root causes resulting from violation of motion economy principles. The
      approach was prospectively tested in 12 observed laparoscopic surgeries performed
      by 5 experienced surgeons. A total of 86 errors were identified and linked to the
      motion economy deficiencies. Results indicate the developed methodology is
      promising. Our methodology allows error prevention in surgery and the developed
      set of motion economy principles could be useful for training surgeons on motion
      economy principles. 

PMID- 25959326
TI  - The effect of user's perceived presence and promotion focus on usability for
      interacting in virtual environments.
AB  - Technological advance in human-computer interaction has attracted increasing
      research attention, especially in the field of virtual reality (VR). Prior
      research has focused on examining the effects of VR on various outcomes, for
      example, learning and health. However, which factors affect the final outcomes?
      That is, what kind of VR system design will achieve higher usability? This
      question remains largely. Furthermore, when we look at VR system deployment from
      a human-computer interaction (HCI) lens, does user's attitude play a role in
      achieving the final outcome? This study aims to understand the effect of
      immersion and involvement, as well as users' regulatory focus on usability for a
      somatosensory VR learning system. This study hypothesized that regulatory focus
      and presence can effectively enhance user's perceived usability. Survey data from
      78 students in Taiwan indicated that promotion focus is positively related to
      user's perceived efficiency, whereas involvement and promotion focus are
      positively related to user's perceived effectiveness. Promotion focus also
      predicts user satisfaction and overall usability perception. 

PMID- 25959327
TI  - Adapting the force characteristics of a staple gun to the human hand.
AB  - Three prototype staple guns with modified force characteristics were compared
      with a commercially available standard staple gun with a linearly increasing
      force resistance during squeezing. The force characteristics of the prototypes
      were more or less adapted to the force characteristics of the human hand, and in
      one of the staple guns the general force level was also reduced by one third.
      Evaluation instruments were electromyography of the forearm flexors and
      extensors, subjective rating of forearm exertion and subjects' free comments
      about the four tools. Twelve professional craftsmen were recruited as test
      subjects. The results show significantly lower readings for two of the three
      prototypes compared with the standard gun in electromyography as well as
      subjective ratings. The squeezing times are also reduced for two of the
      prototypes. It is concluded that the choice of force characteristics of a staple
      gun is important both to minimize forearm muscular exertion and to increase tool
      efficiency. 

PMID- 25959328
TI  - Developing brain-computer interfaces from a user-centered perspective: Assessing
      the needs of persons with amyotrophic lateral sclerosis, caregivers, and
      professionals.
AB  - By focus group methodology, we examined the opinions and requirements of persons
      with ALS, their caregivers, and health care assistants with regard to developing
      a brain-computer interface (BCI) system that fulfills the user's needs. Four
      overarching topics emerged from this analysis: 1) lack of information on BCI and
      its everyday applications; 2) importance of a customizable system that supports
      individuals throughout the various stages of the disease; 3) relationship between
      affectivity and technology use; and 4) importance of individuals retaining a
      sense of agency. These findings should be considered when developing new
      assistive technology. Moreover, the BCI community should acknowledge the need to
      bridge experimental results and its everyday application. 

PMID- 25959329
TI  - Effects of flooring on required coefficient of friction: Elderly adult vs. middle
      aged adult barefoot gait.
AB  - The aim of this study was to investigate the effect of flooring on barefoot gait
      according to age and gender. Two groups of healthy subjects were analyzed: the
      elderly adult group (EA; 10 healthy subjects) and the middle-aged group (MA; 10
      healthy subjects). Each participant was asked to walk at his or her preferred
      speed over two force plates on the following surfaces: 1) homogeneous vinyl
      (HOV), 2) carpet, 3) heterogeneous vinyl (HTV) and 4) mixed (in which the first
      half of the pathway was covered by HOV and the second by HTV). Two force plates
      (Kistler 9286BA) embedded in the data collection room floor measured the ground
      reaction forces and friction. The required coefficient of friction (RCOF) was
      analyzed. For the statistical analysis, a linear mixed-effects model for repeated
      measures was performed. During barefoot gait, there were differences in the RCOF
      among the flooring types during the heel contact and toe-off phases. Due to
      better plantar proprioception during barefoot gait, the EA and MA subjects were
      able to distinguish differences among the flooring types. Moreover, when the EA
      were compared with the MA subjects, differences could be observed in the RCOF
      during the toe-off phase, and gender differences in the RCOF could also be
      observed during the heel contact phase in barefoot gait. 

PMID- 25959330
TI  - Driver discomfort in vehicle seats - Effect of changing road conditions and seat
      foam composition.
AB  - Discomfort in vehicle seats is a multi-factorial problem with contributions
      occurring from effects of sitting duration, seat design, and the dynamic
      environment to which the occupant is exposed. This paper reports laboratory
      studies investigating the extent to which reports of discomfort are affected by
      vibration commencing or ceasing, and whether methods of assessment are sensitive
      enough to detect small changes in foam composition. Study 1 measured discomfort
      ratings for two conditions of 60 min each, comprising 30 min of vibration
      exposure followed by 30 min of static sitting in a car seat, and vice-versa.
      Study 2 measured discomfort ratings for three conditions over a period of 40 min
      each, whilst participants were sitting in one of two car seat compositions, and
      either exposed to vibration or not. In both studies participants operated a
      driving simulator. It is shown that exposure to vibration increases the rate of
      discomfort onset in comparison to periods of static sitting. When vibration
      stopped, there was an acute improvement in comfort but discomfort did not drop to
      the levels reported by those who had been unexposed. When vibration started after
      30 min of static sitting, there was an acute increase in discomfort but not to
      the levels reported by those who had been exposed to 30 min of vibration. After
      40 min of continuous exposure it was possible to detect significant differences
      in overall discomfort between the two seat compositions, although trends could be
      observed in less time.

PMID- 25959331
TI  - Ergonomics Climate Assessment: A measure of operational performance and employee
      well-being.
AB  - Ergonomics interventions have the potential to improve operational performance
      and employee well-being. We introduce a framework for ergonomics climate, the
      extent to which an organization emphasizes and supports the design and
      modification of work to maximize both performance and well-being outcomes. We
      assessed ergonomics climate at a large manufacturing facility twice during a two
      year period. When the organization used ergonomics to promote performance and
      well-being equally, and at a high level, employees reported less work-related
      pain. A larger discrepancy between measures of operational performance and
      employee well-being was associated with increased reports of work-related pain.
      The direction of this discrepancy was not significantly related to work-related
      pain, such that it didn't matter which facet was valued more. The Ergonomics
      Climate Assessment can provide companies with a baseline assessment of the
      overall value placed on ergonomics and help prioritize areas for improving
      operational performance and employee well-being. 

PMID- 25959332
TI  - Postural dynamism during computer mouse and keyboard use: A pilot study.
AB  - Prolonged sedentary computer use is a risk factor for musculoskeletal pain. The
      aim of this study was to explore postural dynamism during two common computer
      tasks, namely mouse use and keyboard typing. Postural dynamism was described as
      the total number of postural changes that occurred during the data capture
      period. Twelve participants were recruited to perform a mouse and a typing task.
      The data of only eight participants could be analysed. A 3D motion analysis
      system measured the number of cervical and thoracic postural changes as well as,
      the range in which the postural changes occurred. The study findings illustrate
      that there is less postural dynamism of the cervical and thoracic spinal regions
      during computer mouse use, when compared to keyboard typing. 

PMID- 25959333
TI  - A field study on thermal comfort in an Italian hospital considering differences
      in gender and age.
AB  - The hospital is a thermal environment where comfort must be calibrated by taking
      into account two different groups of people, that is, patients and medical staff.
      The study involves 30 patients and 19 medical staff with a view to verifying if
      Predicted Mean Vote (PMV) index can accurately predict thermal sensations of both
      groups also taking into account any potential effects of age and gender. The
      methodology adopted is based on the comparison between PMV values (calculated
      according to ISO 7730 after having collected environmental data and estimated
      personal parameters) and perceptual judgments (Actual Mean Vote, AMV), expressed
      by the subjects interviewed. Different statistical analyses show that PMV model
      finds his best correlation with AMV values in a sample of male medical staff
      under 65 years of age. It has been observed that gender and age are factors that
      must be taken into account in the assessment of thermal comfort in the hospital
      due to very weak correlation between AMV and PMV values. 

PMID- 25959334
TI  - The effects of social interactions with in-vehicle agents on a driver's anger
      level, driving performance, situation awareness, and perceived workload.
AB  - Research has suggested that interaction with an in-vehicle software agent can
      improve a driver's psychological state and increase road safety. The present
      study explored the possibility of using an in-vehicle software agent to mitigate
      effects of driver anger on driving behavior. After either anger or neutral mood
      induction, 60 undergraduates drove in a simulator with two types of agent
      intervention. Results showed that both speech-based agents not only enhance
      driver situation awareness and driving performance, but also reduce their anger
      level and perceived workload. Regression models show that a driver's anger
      influences driving performance measures, mediated by situation awareness. The
      practical implications include design guidelines for the design of social
      interaction with in-vehicle software agents. 

PMID- 25959335
TI  - Masking of thresholds for the perception of fore-and-aft vibration of seat
      backrests.
AB  - The detection of a vibration may be reduced by the presence of another vibration:
      a phenomenon known as 'masking'. This study investigated how the detection of one
      frequency of vibration is influenced by vibration at another frequency. With nine
      subjects, thresholds for detecting fore-and-aft backrest vibration were
      determined (for 4, 8, 16, and 31.5-Hz sinusoidal vibration) in the presence of a
      masker vibration (4-Hz random vibration, 1/3-octave bandwidth at six
      intensities). The masker vibration increased thresholds for perceiving vibration
      at each frequency by an amount that reduced with increasing difference between
      the frequency of the sinusoidal vibration and the frequency of the masker
      vibration. The 4-Hz random vibration almost completely masked 4-Hz sinusoidal
      vibration, partially masked 8- and 16-Hz vibration, and only slightly masked 31.5
      Hz vibration. The findings might be explained by the involvement of different
      sensory systems and different body locations in the detection of different
      frequencies of vibration. 

PMID- 25959337
TI  - Assessing the performance of winter footwear using a new maximum achievable
      incline method.
AB  - More informative tests of winter footwear performance are required in order to
      identify footwear that will prevent injurious slips and falls on icy conditions.
      In this study, eight participants tested four styles of winter boots on smooth
      wet ice. The surface was progressively tilted to create increasing longitudinal
      and cross-slopes until participants could no longer continue standing or walking.
      Maximum achievable incline angles provided consistent measures of footwear slip
      resistance and demonstrated better resolution than mechanical tests. One footwear
      outsole material and tread combination outperformed the others on wet ice
      allowing participants to successfully walk on steep longitudinal slopes of 17.5
      degrees  +/- 1.9 degrees  (mean +/- SD). By further exploiting the methodology to
      include additional surfaces and contaminants, such tests could be used to
      optimize tread designs and materials that are ideal for reducing the risk of
      slips and falls. 

PMID- 25959336
TI  - Multi-parameter prediction of drivers' lane-changing behaviour with neural
      network model.
AB  - Accurate prediction of driving behaviour is essential for an active safety system
      to ensure driver safety. A model for predicting lane-changing behaviour is
      developed from the results of naturalistic on-road experiment for use in a lane
      changing assistance system. Lane changing intent time window is determined via
      visual characteristics extraction of rearview mirrors. A prediction index system
      for left lane changes was constructed by considering drivers' visual search
      behaviours, vehicle operation behaviours, vehicle motion states, and driving
      conditions. A back-propagation neural network model was developed to predict lane
      changing behaviour. The lane-change-intent time window is approximately 5 s long,
      depending on the subjects. The proposed model can accurately predict drivers'
      lane changing behaviour for at least 1.5 s in advance. The accuracy and time
      series characteristics of the model are superior to the use of turn signals in
      predicting lane-changing behaviour. 

PMID- 25959338
TI  - Quantitative evaluation of the impact of night shifts and alcohol consumption on
      construction tiling quality.
AB  - The adverse effects of night-shift work and alcohol consumption on performance
      have received considerable attention. However, how night shifts and alcohol
      affect productivity in workers has not been quantified. This paper describes the
      experiments featuring multiple tiling tasks and patterns. The tiling quality
      performed by the graduate student participants in four different statuses was
      objectively evaluated by an edge-detection computer program. The results indicate
      that both night shift and alcohol significantly reduce the quality in general,
      and the effects of the factors on position and alignment-angle qualities were
      dissimilar in distinct areas due to tile patterns and size. Both night-shift and
      alcohol conditions affected the basic (-34.01% and -25.79%) and advanced tiling
      abilities (-40.14% and -26.16%), and night shift had a larger impact than
      alcohol. These results provide jobsite managers with usable information regarding
      how night shifts and alcohol affect workers' abilities to execute basic and
      advanced tasks. 

PMID- 25959339
TI  - The influence of footwear tread groove parameters on available friction.
AB  - The purpose of this study was to determine how footwear tread groove parameters
      influence available friction (COF). Utilizing a whole shoe tester (SATRA STM
      603), 3 groove parameters (width, depth and orientation) were evaluated. Groove
      orientation had 3 levels (parallel, oblique and perpendicular), width had 3
      levels (3, 6 and 9 mm) and depth had 3 levels (2, 4 and 6 mm). In total, the COF
      of 27 shoes, each with a distinct groove combination, was assessed on wet
      porcelain tile. The 27 groove combinations produced a wide range of COF values
      (0.080-0.344). Groove orientation had the greatest impact on COF, explaining the
      greatest variance in observed COF values (n(2) = 0.81). The most slip resistant
      groove combination was an oblique orientation, with 3 mm width and 2 mm depth.
      The least slip resistant groove combination was a parallel orientation, with a 6
      mm width and 6 mm depth.

PMID- 25959340
TI  - Impact of online training on delivering a difficult medical diagnosis: Acquiring
      communication skills.
AB  - This paper deals with developing and assessing the training of physicians to
      deliver a difficult diagnosis to patients. The training is provided by a web
      based self-training package. This online training emphasizes the structural,
      functional and relational dimensions of interviews delivering a serious
      diagnosis, and a logical set of recommendations for behavior towards the patient.
      The content is illustrated by numerous delivery interview sequences that are
      described and for which commentary is provided. This online package was expected
      to enable physicians to acquire new skills and change their mental picture of
      diagnosis delivery. Here we discuss the assessment of training in managing the
      delivery of a serious diagnosis. The approach taken and the methods used to
      measure knowledge and skills are presented. 

PMID- 25959341
TI  - Movement transformation on multi-touch devices: Intuition or instructional
      preparation?
AB  - Multi-touch technology is a key part of computer interaction today, yet little is
      known about the distinction between direct and indirect input devices in terms of
      intuitive interaction. An experimental study aims to identify the difficulties of
      interaction with indirect multi-touch devices by applying the action regulation
      theory and the principle of movement transformation to common computer tasks
      involving gesture utilization. An analysis of the data acquired from 54 subjects
      working with an Apple Magic Trackpad implies that gestures on indirect multi
      touch devices are not utilized intuitively without instructions that bypass
      conceptual difficulties of indirect gesture usage. It is shown that gesture use
      influences product assessment measured by User Experience questionnaires and that
      prior experience with direct multi-touch devices does not influence gesture usage
      or product assessment. We advise that product developers utilize video
      instructions to create a sense of intuitive interaction. 

PMID- 25959342
TI  - New material of Pseudoloris parvulus (Microchoerinae, Omomyidae, Primates) from
      the Late Eocene of Sossis (northeastern Spain) and its implications for the
      evolution of Pseudoloris.
AB  - The species Pseudoloris parvulus, identified in several Middle and Late Eocene
      European sites, was previously known in the Iberian Peninsula by a single
      mandible preserving P4-M3 from Sossis (Southern Pyrenean Basins, northeastern
      Spain), described in the 1960s. Further field work at this Late Eocene site has
      led to the recovery of a large number of mammal remains, including the additional
      material of P. parvulus described in this paper. Some specimens of P. parvulus
      from this locality have also been recently found in the collections of the
      Naturhistorisches Museum Basel, Switzerland. The whole sample consists of 11
      mandible fragments including several teeth, three upper dental series and nearly
      80 isolated teeth including all of the dental elements, and represents the most
      complete sample of the genus described from the Iberian Peninsula. This abundant
      material allows us to provide an emended diagnosis for the species and to observe
      several directional changes in the dental morphology of the lineage including the
      species Pseudoloris saalae, Pseudoloris isabenae, Pseudoloris pyrenaicus and P.
      parvulus. These directional changes include the progressive reduction of the
      paraconid in the lower molars and the increase in size of the hypocone,
      metaconule and paraconule in the upper molars. Moreover, despite the overall
      resemblance among all of the samples ascribed to P. parvulus, we also recognize
      some differences, particularly an increase in size and better development of the
      hypocone from the oldest populations of the species, such as Le Bretou, to the
      most recent ones, like Sossis and Perriere. Therefore, this study sheds new light
      on the evolution of this genus, which inhabited Europe from the Middle Eocene to
      the Early Oligocene. 

PMID- 25959343
TI  - Interpersonal strategies for disturbance attenuation during a rhythmic joint
      motor action.
AB  - Helping someone carry a table is fairly easy; however, our understanding of such
      joint motor actions is still poorly understood. We studied how pairs of human
      subjects (referred to as dyads) collaborate physically to attenuate external
      mechanical perturbations during a target tracking task. Subjects tracked a target
      moving in a slow and predictable way using wrist flexion/extension movements,
      with and without destabilizing torque perturbations. Dyad strategies were
      classified using interaction torques and muscular activity. During unperturbed
      interactions (baseline), the dyads tended to stabilize on a particular strategy.
      The baseline strategy was not the same in all dyads, suggesting that the solution
      to the task was not global but specific to each particular dyad. After several
      trials of unperturbed interactions, we introduced mechanical vibrations and
      analyzed the adaptation process. Dyads showed a tendency to counteract the
      external disturbances by first increasing co-contraction within each subject
      (independent co-contraction), and then raising the amount of opposing interaction
      torques (dyadic co-contraction) with increased perturbation amplitude. The
      introduction of perturbations impelled dyads to abandon their unperturbed
      baseline strategy and adopt a more common strategy across dyads, suggesting
      attractor solutions. Our results establish a framework for future human-human
      interaction studies, and have implications in human motor control as well as
      human-robot and robot-robot interactions. 

PMID- 25959344
TI  - Perspectives.

PMID- 25959345
TI  - Evidence, errors, and ethics.
AB  - Evidence-based decisions relating to the development and use of novel medical
      interventions are liable to false positive and false negative errors: adverse
      consequences that ensue from making or omitting to make a given decision. In this
      article we examine the propensity to false positive and false negative errors in
      light of competing value judgments in the areas of designing randomized
      controlled trials, pharmaceutical licensing, coverage of medical treatments, and
      clinical practice. 

PMID- 25959346
TI  - The integration of social, behavioral, and biological mechanisms in models of
      pathogenesis.
AB  - A large part of contemporary medicine is concerned with describing and
      understanding the biological mechanisms involved in disease causation.
      Comparatively less attention has been paid to the socioeconomic and behavioral
      mechanisms underlying disease. This article argues for an integration of social,
      behavioral, and biological factors in the explanation of pathogenesis, a
      perspective that is in accord with the vision of pioneer public health
      practitioners of the 19th century, but that has gradually been overtaken by the
      dominance of the biomedical disease model. In recent decades, the social
      components of disease have been depicted as "distal" factors or used as
      "classificatory" devices. We explain how the integration we propose, which draws
      upon the concepts of "mixed mechanism" and of "lifeworld," advances the view of
      several scholars of the recent past. Finally, we discuss new findings in
      epigenetics and psychology, where socioeconomic disparities appear to be an
      integral part of the explanation of health conditions, to illustrate how the
      integration may work in practice. 

PMID- 25959347
TI  - Fighting for Dear Life: Christians and Aggressive End-of-Life Care.
AB  - Patients or their family members sometimes give religious reasons for requesting
      life-sustaining technologies that have little hope of restoring health. This
      poses an ethical challenge for clinicians and a potential strain on limited
      health-care resources. Among Christians, one explanation for a preference for
      aggressive, life-prolonging care is the influence of the idea of martyrdom, which
      became the normative form of dying in early Christianity. The ancient discourse
      of martyrdom and the modern discourse of aggressive medical care both share a
      martial orientation and commend an ethos of combat. This paper examines ancient
      Christian martyrdom discourse to illuminate its affinity with the discourse of
      aggressive medical care. The ethos of martyrdom has shaped Christian attitudes
      toward death such that preference for aggressive medical care at the end of life
      is understandable. 

PMID- 25959348
TI  - Peabody's "Care of the Patient" and the Nature of Medical Science.
AB  - Francis W. Peabody's 1927 essay "The Care of the Patient" is widely quoted, yet
      few appreciate the subtlety of its interweaving of medical science with its more
      obvious humanistic elements. Understanding the essay in context requires a
      recapitulation of Peabody's life story, a review of earlier work that led up to
      the culminating lecture in 1926, and a detailed analysis of the thread of
      argument Peabody wove through the lecture. A better understanding of the essay
      shows how Peabody anticipated several important later developments in medical
      thought. 

PMID- 25959349
TI  - A bittersweet story: the true nature of the laurel of the Oracle of Delphi.
AB  - It is known from ancient sources that "laurel," identified with sweet bay, was
      used at the ancient Greek oracle of Delphi. The Pythia, the priestess who spoke
      the prophecies, purportedly used laurel as a means to inspire her divine frenzy.
      However, the clinical symptoms of the Pythia, as described in ancient sources,
      cannot be attributed to the use of sweet bay, which is harmless. A review of
      contemporary toxicological literature indicates that it is oleander that causes
      symptoms similar to those of the Pythia, while a closer examination of ancient
      literary texts indicates that oleander was often included under the generic term
      laurel. It is therefore likely that it was oleander, not sweet bay, that the
      Pythia used before the oracular procedure. This explanation could also shed light
      on other ancient accounts regarding the alleged spirit and chasm of Delphi,
      accounts that have been the subject of intense debate and interdisciplinary
      research for the last hundred years. 

PMID- 25959350
TI  - Give me a break: Gerhard Kuntscher and his nail.
AB  - The treatment of broken bones has long adhered to principles of tight
      juxtaposition of fracture ends and of strict rest. Splinting and casting with
      plaster of Paris helped considerably. Attempts at internal splinting with pegs,
      bolts, or stabilizing contraptions usually failed. Foreign materials were either
      not biocompatible or broke easily, and the insertion of these prostheses directly
      into the fracture created additional risks from infections. All this changed when
      Gerhard Kuntscher (1900-1972) stabilized broken long bones by intramedullary
      insertion of stainless steel nails through a small incision, distant from the
      fracture. Kuntscher employed his method from the late 1930s on, initially as a
      surgeon at the Kiel University in Germany. His early and encouraging results were
      rejected when presented in 1940, and he remained ostracized thenceforth. During
      WWII he was stationed in Finland, where he treated wounded soldiers from both
      sides of the front. POWs returning home propagated the new method by revealing
      these rods in roentgenograms of their legs; had he not been so successful in
      treating POWs, he might have had to stand trial at the Nuremberg Doctors' Trial
      (1947). He documented his experiments and experiences in more than 200 articles
      and three monographs. Today, his method is employed universally. 

PMID- 25959351
TI  - When Harvard said no to eugenics: the J. Ewing Mears Bequest, 1927.
AB  - James Ewing Mears (1838-1919) was a founding member of the Philadelphia Academy
      of Surgery. His 1910 book, The Problem of Race Betterment, laid the groundwork
      for later authors to explore the uses of surgical sterilization as a eugenic
      measure. Mears left $60,000 in his will to Harvard University to support the
      teaching of eugenics. Although numerous eugenic activists were on the Harvard
      faculty, and two of its Presidents were also associated with the eugenics
      movement, Harvard refused the Mears gift. The bequest was eventually awarded to
      Jefferson Medical College in Philadelphia. This article explains why Harvard
      turned its back on a donation that would have supported instruction in a popular
      subject. Harvard's decision illustrates the range of opinion that existed on the
      efficacy of eugenic sterilization at the time. The Mears case also highlights a
      powerful irony: the same week Harvard turned down the Mears legacy, the U.S.
      Supreme Court endorsed eugenic sterilization in the landmark case of Buck v.
      Bell. Justice Oliver Wendell Holmes, Jr., graduate of Harvard and former member
      of its law faculty wrote the opinion in that case, including the famous
      conclusion: "Three generations of imbeciles are enough." 

PMID- 25959352
TI  - Religion in Organized Medicine: The AMA's Committee and Department of Medicine
      and Religion, 1961-1974.
AB  - The history commonly told of the relationship between modern medicine and
      religion is one of steady, even inevitable, separation rooted in the
      Enlightenment. The divorce between medicine and religion, it is thought, had
      become nearly total before a recent surge of interest in the spiritual and
      religious dimensions of health care. This narrative, however, misjudges a
      persistent sense of spiritual need in illness that medical practice, even today,
      is unable to entirely ignore. Relying on primary sources, we recount here the
      little known story of the rise and fall of the Committee on Medicine and Religion
      and the Department of Medicine and Religion at the American Medical Association
      between 1961 and 1974. Arising in a context of a widely perceived dehumanization
      of care and the emergence of new ethical dilemmas at the bedside--concerns with
      significant parallels today--the initiative garnered striking physician
      enthusiasm and achieved dramatic successes nationally before coming to a puzzling
      end in 1972. We argue that its demise was linked to the AMA's contentious
      internal debate on abortion, and conclude with a note of caution regarding the
      status of normative concerns in medicine's ongoing efforts to address the
      spiritual and religious dimensions of its practices.

PMID- 25959353
TI  - Opiate written behavioral agreements: a case for abandonment.
AB  - Written behavioral agreements (WBAs) are gaining popularity as part of the effort
      to manage the alarming increase in prescription drug abuse. The rationale for
      increased use of WBAs in managing patients with chronic pain is that they are
      believed to increase adherence to agreed-upon behaviors, reduce addiction to or
      diversion of prescription drugs, and satisfy informed consent requirements.
      However, there are no high-quality data to support their widespread use in any of
      these areas. The evidence used to support the use of WBAs is insufficient to
      justify their unfairness and the high risk of harm they pose to the doctor
      patient relationship. Instead, we contend that WBAs are being used to provide
      leverage for severing relationships with some of our most challenging patients.
      We propose that physicians treating patients for chronic pain abandon the use of
      WBAs. Alternatives include open communication, detailed informed consent
      processes, carefully documented discussions, and most important, commitment to
      ongoing relationships even with difficult patients. 

PMID- 25959354
TI  - Languages of the heart: the biomedical and the metaphorical in American fiction.
AB  - The role of heart disease in American fiction has received less attention from
      scholars of literature, history, and medicine than have portrayals of
      tuberculosis, cancer, or HIV/AIDS, despite the fact that heart disease topped
      mortality charts for most of the 20th century. This article surveys
      manifestations of coronary artery disease in popular works of 20th-century
      American fiction to trace how authors and their protagonists grappled with the
      disease while knowledge of pathophysiology and therapeutics evolved. Countering
      Susan Sontag's mechanistic vision of patient encounters-where disease is absent
      of metaphor-we pair popular fiction with concurrent historical analysis to show
      that the proliferation of technological narratives of cardiac therapeutics could
      not displace the deeply symbolic nature of characters' encounters with heart
      disease. Because of the limited ability of the biomedical narrative to convey the
      meanings of disease and treatments, doctors and patients need to communicate
      through the rich possibilities of metaphor. 

PMID- 25959355
TI  - Different risk factor profiles distinguish early-onset from late-onset BKV
      replication.
AB  - Two of three reactivations of latent BKV-infection occur within the first 6
      months after renal transplantation. However, a clear differentiation between
      early-onset and late-onset BKV-replication is lacking. Here, we studied all
      kidney transplant recipients (KTRs) at our single transplant center between 2004
      and 2012. A total of 103 of 862 KTRs were diagnosed with BK viremia (11.9%),
      among which 24 KTRs (2.8%) showed progression to BKV-associated nephropathy
      (BKVN). Sixty-seven KTRs with early-onset BKV-replication (65%) and 36 KTRs with
      late-onset BKV-replication (35%) were identified. A control group of 598 KTRs
      without BKV-replication was used for comparison. Lymphocyte-depleting induction,
      CMV-reactivation, and acute rejection increased the risk of early-onset BKV
      replication (P < 0.05). Presensitized KTRs undergoing renal retransplantation
      were those at increased risk of late-onset BKV-replication (P < 0.05). Among KTRs
      with BK viremia, higher doses of mycophenolate increased the risk of progression
      to BKVN (P = 0.004). KTRs with progression to BKVN showed inferior allograft
      function (P < 0.05). KTRs with late-onset BK viremia were more likely not to
      recover to baseline creatinine after BKV-replication (P = 0.018). Our data
      suggest different risk factors in the pathogenesis of early-onset and late-onset
      BKV-reactivation. While a more intensified immunosuppression is associated with
      early-onset BKV-replication, a chronic inflammatory state in presensitized KTRs
      may contribute to late-onset BKV-replication. 

PMID- 25959356
TI  - Alkane Activation Initiated by Hydride Transfer: Co-conversion of Propane and
      Methanol over H-ZSM-5 Zeolite.
AB  - Co-conversion of alkane with another reactant over zeolite catalysts has emerged
      as a new approach to the long-standing challenge of alkane transformation. With
      the aid of solid-state NMR spectroscopy and GC-MS analysis, it was found that the
      co-conversion of propane and methanol can be readily initiated by hydride
      transfer at temperatures of >=449 K over the acidic zeolite H-ZSM-5. The
      formation of (13)C-labeled methane and singly (13)C-labeled n-butanes in
      selective labeling experiments provided the first evidence for the initial
      hydride transfer from propane to surface methoxy intermediates. The results not
      only provide new insight into carbocation chemistry of solid acids, but also shed
      light on the low-temperature transformation of alkanes for industrial
      applications.

PMID- 25959357
TI  - Does a male operator increase the pain perception of women undergoing
      hysterosalpingography examination?

PMID- 25959358
TI  - Acute simultaneous multiple lacunar infarcts as the initial presentation of
      cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is an adult-onset, dominantly inherited small
      vessel disease of the brain caused by NOTCH3 mutations and characterized by
      recurrent subcortical infarctions, dementia, migraine with aura, and mood
      disturbance. We report a patient with unusual presentation of CADASIL with acute
      simultaneous multiple subcortical lacunar infarcts as the first manifestation. A
      69-year-old man developed confusion, drowsiness, right hemiparesis, and slurred
      speech following orthopedic surgeries. Brain magnetic resonance imaging revealed
      diffuse leukoencephalopathy and multiple acute subcortical lacunar infarcts.
      Brain magnetic resonance angiography, echocardiography and 24-hour
      electrocardiography were unremarkable. The symptoms improved quickly after
      treatment with fluid hydration and antiplatelet agent, and his consciousness and
      mentality totally recovered within 3 days. The NOTCH3 genetic testing showed a
      heterozygous missense mutation, c.1630C>T (p. Arg544Cys). The experience in this
      case suggests that brain imaging is important in managing postoperative
      confusion, and any patient with diffuse leukoencephalopathy of unknown etiology
      may need to be tested for NOTCH3 mutations. Surgery is an important factor of
      encephalopathy and acute infarction in individuals with NOTCH3 mutations.
      Comprehensive presurgical evaluations and proactive perioperative precautions to
      avoid dehydration and anemia are necessary for patients with CADASIL who are
      about to receive anesthesia and surgery. 

PMID- 25959359
TI  - Force generation and transmission in keloid fibroblasts: dissecting the role of
      mechanosensitive molecules in cell function.

PMID- 25959361
TI  - Neural network iterative diagonalization method to solve eigenvalue problems in
      quantum mechanics.
AB  - We propose a multi-layer feed-forward neural network iterative diagonalization
      method (NNiDM) to compute some eigenvalues and eigenvectors of large sparse
      complex symmetric or Hermitian matrices. The NNiDM algorithm is developed by
      using the complex (or real) guided spectral transform Lanczos (cGSTL) method,
      thick restart technique, and multi-layered basis contraction scheme. Artificial
      neurons (or nodes) are defined by a set of formally orthogonal Lanczos
      polynomials, where the biases and weights are dynamically determined through a
      series of cGSTL iterations and small matrix diagonalizations. The algorithm
      starts with one random vector. The last output layer produces wanted eigenvalues
      and eigenvectors near a given reference value via a linear transform
      diagonalization approach. Since the algorithm uses the spectral transform
      technique, it is capable of computing interior eigenstates in dense spectrum
      regions. The general NNiDM algorithm is applied for calculating energies, widths,
      and wavefunctions of two typical molecules HO2 and CH4 as examples. 

PMID- 25959360
TI  - Real-time quantitative reverse transcription-polymerase chain reaction to detect
      propionibacterial ribosomal RNA in the lymph nodes of Chinese patients with
      sarcoidosis.
AB  - The aim of this study was to investigate the diagnostic value of using the copy
      number of propionibacterial rRNA as a biomarker for sarcoidosis. Ribosomal RNA of
      Propionibacterium acnes and P. granulosum was measured by real-time quantitative
      reverse transcription-polymerase chain reaction (RT-PCR) using formalin-fixed and
      paraffin-embedded tissue of lymph node biopsy from 65 Chinese patients with
      sarcoidosis, 45 with tuberculosis and 50 controls with other diseases (23 with
      non-specific lymphadenitis and 27 with mediastinal lymph node metastasis from
      lung cancer). The receiver operating characteristic (ROC) curve was analysed to
      determine an optimal cut-off value for diagnosis, and the diagnostic accuracy of
      the cut-off value was evaluated in additional tissue samples [24 patients with
      sarcoidosis and 22 with tuberculosis (TB)]. P. acnes or P. granulosum rRNA was
      detected in 48 of the 65 sarcoidosis samples but only in four of the 45 TB
      samples and three of the 50 control samples. Analysis of the ROC curve revealed
      that an optimal cut-off value of the copy number of propionibacterial rRNA for
      diagnosis of sarcoidosis was 50.5 copies/ml with a sensitivity and specificity of
      73.8 and 92.6%, respectively. Based on the cut-off value, 19 of the 24 additional
      sarcoidosis samples exhibited positive P. acnes or P. granulosum, whereas only
      one of the 22 additional TB samples was positive, resulting in a sensitivity and
      specificity of 79.2 and 95.5%, respectively. These findings suggest that
      propionibacteria might be associated with sarcoidosis granulomatous inflammation.
      Detection of propionibacterial rRNA by RT-PCR might possibly distinguish
      sarcoidosis from TB. 

PMID- 25959362
TI  - A dendrimer-assisted magnetic graphene-silica hydrophilic composite for efficient
      and selective enrichment of glycopeptides from the complex sample.
AB  - Combining high surface area, numerous active sites, strong magnetic response,
      multivalent synergistic binding effects and outstanding hydrophilicity, a novel
      hydrophilic composite demonstrated efficient and selective enrichment of
      glycopeptides from the complex sample. 

PMID- 25959363
TI  - Formation of a columnar liquid crystal in a simple one-component system of
      particles.
AB  - We report a molecular dynamics simulation demonstrating that a columnar liquid
      crystal, commonly formed by disc-shaped molecules, can be formed by identical
      particles interacting via a spherically symmetric potential. Upon isochoric
      cooling from a low-density isotropic liquid state the simulated system underwent
      a weak first order phase transition which produced a liquid crystal phase
      composed of parallel particle columns arranged in a hexagonal pattern in the
      plane perpendicular to the column axis. The particles within columns formed a
      liquid structure and demonstrated a significant intracolumn diffusion. Further
      cooling resulted in another first-order transition whereby the column structure
      became periodically ordered in three dimensions transforming the liquid-crystal
      phase into a crystal. This result is the first observation of a columnar liquid
      crystal formation in a simple one-component system of particles. Its conceptual
      significance is in that it demonstrated that liquid crystals that have so far
      only been produced in systems of anisometric molecules can also be formed by
      mesoscopic soft-matter and colloidal systems of spherical particles with
      appropriately tuned interatomic potential. 

PMID- 25959365
TI  - Iron-mediated C-H coupling of arenes and unactivated terminal alkenes directed by
      sulfur.
AB  - A sulfur-directed Fe(iii)-mediated ortho C-H coupling of arenes with unactivated
      terminal alkenes gives products of regioselective alkene chloroarylation. The
      novel mechanism involves redox-activation of the arene partner and alkene
      addition to the resultant aryl radical cation. 

PMID- 25959364
TI  - Interstitial high-dose-rate brachytherapy in eyelid cancer.
AB  - PURPOSE: To report the experience and the outcomes of interstitial high-dose-rate
      (HDR) brachytherapy (BT) of eyelid skin cancer at the Department of Radiotherapy
      of Hospital de Santa Maria in Lisbon. METHODS AND MATERIALS: Seventeen patients
      (pts; mean age, 73.75 years) who underwent eyelid interstitial HDR BT with an
      (192)Ir source between January 2011 and February 2013 were analyzed. Lesions were
      basal (94%) and squamous (6%) cell carcinomas, on lower (88%) or upper (6%)
      eyelids, and on inner canthus (6%). T-stage was Tis (6%), T1 (46%), T2 (36%), and
      T3a (12%). The purpose of BT was radical (12%), adjuvant to surgery (71%), or
      salvage after surgery (18%). The BT implant and treatment planning were based on
      the Stepping Source Dosimetry System. The median total dose was 42.75 Gy (range,
      32-50 Gy), with a median of 10 fractions (range, 9-11 fractions), twice daily, 6
      h apart. The median V100 was 2.38 cm(3) (range, 0.83-5.59 cm(3)), and the median
      V150 was 1.05 cm(3) (range, 0.24-3.12 cm(3)). RESULTS: At a median followup of 40
      months (range, 7-43 months), the local control was 94.1%. There was one local
      recurrence and one non-related death. The BT was well tolerated. Madarosis was
      the most common late effect (65% of pts) and was related with higher values of
      V100 (p = 0.027). Cosmetic outcomes were good and excellent in 70% of pts.
      CONCLUSIONS: Interstitial HDR BT is a feasible and safe technique for eyelid skin
      cancers, with good local control. Recurrent lesions and higher volumes receiving
      the prescribed dose were associated with worse outcomes.

PMID- 25959366
TI  - Virtuous laughter: we should teach medical learners the art of humor.
AB  - There is increasing recognition of the stress and burnout suffered by critical
      care workers. Physicians have a responsibility to teach learners the skills
      required not only to treat patients, but to cope with the demands of a stressful
      profession. Humor has been neglected as a strategy to help learners develop into
      virtuous and resilient physicians. Humor can be used to reduce stress, address
      fears, and to create effective health care teams. However, there are forms of
      humor which can be hurtful or discriminatory. In order to maximize the benefits
      of humor and to reduce its harms, we need to teach and model the effective and
      virtuous use of humor in the intensive care unit. 

PMID- 25959367
TI  - Enhanced biofilm formation and melanin synthesis by the oyster settlement
      promoting Shewanella colwelliana is related to hydrophobic surface and simulated
      intertidal environment.
AB  - A direct relationship between biofilm formation and melanogenesis in Shewanella
      colwelliana with increased oyster recruitment is already established. Previously,
      S. colwelliana was grown in a newly patented biofilm-cultivation device, the
      conico-cylindrical flask (CCF), offering interchangeable hydrophobic/hydrophilic
      surfaces. Melanization was enhanced when S. colwelliana was cultivated in a
      hydrophobic vessel compared with a hydrophilic vessel. In the present study,
      melanogenesis in the CCF was positively correlated with increased architectural
      parameters of the biofilm (mean thickness and biovolume obtained by confocal
      laser scanning microscopy) and melanin gene (melA) expression observed by
      densitometry. Niche intertidal conditions were mimicked in a process operated in
      an ultra-low-speed rotating disk bioreactor, which demonstrated enhanced biofilm
      formation, melanogenesis, exopolysaccharide synthesis and melA gene expression
      compared with a process where 12-h periodic immersion and emersion was prevented.
      The wettability properties of the settling plane as well as intermittent wetting
      and drying, which influenced biofilm formation and melA expression, may affect
      oyster settlement in nature. 

PMID- 25959368
TI  - Bacterial patterning at the three-phase line of contact with microtextured
      alkanes.
AB  - Aliphatic crystallites, characteristic of the eicosane and docosane components of
      naturally occurring lipids, were found to form microtextures that were structured
      by specific interactions with ordered graphite (HOPG) used as the underlying
      substratum, as confirmed by scanning electron microscopy (SEM) and fast Fourier
      transform (FFT) analysis. Confocal scanning laser microscopy (CLSM) showed highly
      directed bacterial alignment for two bacterial species (spherical and rod
      shaped), reflecting the preferential orientation of the crystallite-air-water
      interfaces to give linear and triangular bacterial patterning. The mechanisms of
      bacterial attachment are demonstrated in terms of the balance between effective
      radial adhesional forces and the capillary forces resulting from the water
      contact angle of the bacteria at the three-phase line (TPL) of the lipid surface.
      It is suggested that these microtextured surfaces, which exhibit the ability to
      limit bacterial adhesion to a precise patterning at the lipid TPL, could be used
      as a means of controlling bacterial colonization. 

PMID- 25959371
TI  - Inhibitor-based affinity probes for the investigation of JAK signaling pathways.
AB  - The Janus Kinase (JAK) signaling pathway plays a key role for many cellular
      processes and has recently been correlated with neuronal disorders. In order to
      understand new links of JAK family members with other signaling pathways,
      chemical proteomics tools with broad kinase coverage are desirable. A probe that
      shows outstanding kinase selectivity and allows for the enrichment of up to 133
      kinases including many mitogen activated kinase (MAPK) members and JAK kinases
      has been developed. Furthermore, this probe was applied to establish the
      selectivity profile of the JAK1/2 inhibitor momelotinib that is currently
      evaluated in clinical phase 3 studies. These results render this probe a valuable
      tool for the investigation of JAK and JAK related signaling pathways and the
      selectivity profiling of kinase inhibitors. 

PMID- 25959372
TI  - Conjugating influenza a (H1N1) antigen to n-trimethylaminoethylmethacrylate
      chitosan nanoparticles improves the immunogenicity of the antigen after nasal
      administration.
AB  - As one of the most serious infectious respiratory diseases, influenza A (H1N1) is
      a great threat to human health, and it has created an urgent demand for effective
      vaccines. Nasal immunization can induce both systemic and mucosal immune
      responses against viruses, and it can serve as an ideal route for vaccination.
      However, the low immunogenicity of antigens on nasal mucosa is a high barrier for
      the development of nasal vaccines. In this study, we covalently conjugated an
      influenza A (H1N1) antigen to the surface of N-trimethylaminoethylmethacrylate
      chitosan (TMC) nanoparticles (H1N1-TMC/NP) through thioester bonds to increase
      the immunogenicity of the antigen after nasal administration. SDS-PAGE revealed
      that most of the antigen was conjugated on TMC nanoparticles, and an in vitro
      biological activity assay confirmed the stability of the antigen after
      conjugation. After three nasal immunizations, the H1N1-TMC/NP induced
      significantly higher levels of serum IgG and mucosal sIgA compared with free
      antigen. A hemagglutination inhibition assay showed that H1N1-TMC/NP induced much
      more protective antibodies than antigen-encapsulated nanoparticles or alum
      precipitated antigen (I.M.). In the mechanistic study, H1N1-TMC/NP was shown to
      stimulate macrophages to produce IL-1beta and IL-6 and to stimulate spleen
      lymphocytes to produce IL-2 and IFN-gamma. These results indicated that H1N1
      TMC/NP may be an effective vaccine against influenza A (H1N1) viruses for use in
      nasal immunization.

PMID- 25959370
TI  - Neutrophil extracellular trap formation in supragingival biofilms.
AB  - BACKGROUND: Oral biofilms are the causative agents of the highly prevalent oral
      diseases periodontitis and caries. Additionally, the host immune response is
      thought to play a critical role in disease onset. Neutrophils are known to be a
      key host response factor to bacterial challenge on host surfaces. Release of
      neutrophil extracellular traps (NETs) as a novel antimicrobial defense strategy
      has gained increasing attention in the past years. Here, we investigated the
      influx of neutrophils into the dental plaque and the ability of oral bacteria to
      trigger intra-biofilm release of NETs and intracellular proteins. METHODS:
      Supragingival biofilms and whole saliva were sampled from systemically healthy
      subjects participating in an experimental gingivitis study. Biofilms were
      analysed by immunofluorescence followed by confocal and fluorescence microscopy.
      Moreover, concentrations of cytokines and immune-associated proteins in biofilm
      suspensions and saliva were assessed by ELISA. Neutrophils obtained from blood
      were stimulated with twelve bacterial species isolated from cultured biofilms or
      with lipopolysaccharide to monitor NET formation. RESULTS: Neutrophils, NETs,
      neutrophil-associated proteins (myeloperoxidase, elastase-2, cathepsin G,
      cathelicidin LL-37), interleukin-8, interleukin-1beta and tumor necrosis factor
      were detected within plaque samples and saliva. All tested bacterial species as
      well as the polymicrobial samples isolated from the plaque of each donor induced
      release of NETs and interleukin-8. The degree of NET formation varied among
      different subjects and did not correlate with plaque scores or clinical signs of
      local inflammation. CONCLUSIONS: Our findings indicate that neutrophils are
      attracted towards dental biofilms, in which they become incorporated and where
      they are stimulated by microbes to release NETs and immunostimulatory proteins.
      Thus, neutrophils and NETs may be involved in host biofilm control, although
      their specific role needs to be further elucidated. Moreover, inter-patient
      variability suggests NET formation as a potential factor influencing the
      individual course of disease.

PMID- 25959375
TI  - Partial dark-field microscopy for investigating domain structures of double-layer
      microsphere film.
AB  - A lateral dislocation in a double-layer microsphere film is very difficult to
      identify because the constituent domains have the same two-dimensional
      crystalline orientation. Orientation-sensitive optical techniques cannot resolve
      this issue. Here, we demonstrate that partial dark-field (pDF) optical microscopy
      can be very effective in identifying this type of domain boundary and dislocation
      of a close-packed microsphere double-layer. Using the hexagonal symmetry of the
      close-packed microsphere film and the light-focusing property of microspheres,
      the partially blocked dark-field condenser can provide much higher contrast than
      other optical microscopy modes can in identifying the laterally dislocated
      domains. The former can also distinguish domains with different crystalline
      orientation by rotating the pDF stop. The simplicity of the pDF mode will make it
      an ideal tool for the structural study of close-packed double-layer microsphere
      films. 

PMID- 25959373
TI  - Kaempferol ameliorates symptoms of metabolic syndrome by regulating activities of
      liver X receptor-beta.
AB  - Kaempferol is a dietary flavonol previously shown to regulate cellular lipid and
      glucose metabolism. However, its molecular mechanisms of action and target
      proteins have remained elusive, probably due to the involvement of multiple
      proteins. This study investigated the molecular targets of kaempferol. Ligand
      binding of kaempferol to liver X receptors (LXRs) was quantified by time-resolved
      fluorescence resonance energy transfer and surface plasmon resonance analyses.
      Kaempferol directly binds to and induces the transactivation of LXRs, with
      stronger specificity for the beta-subtype (EC50 = 0.33 MUM). The oral
      administration of kaempferol in apolipoprotein-E-deficient mice (150 mg/day/kg
      body weight) significantly reduced plasma glucose and increased high-density
      lipoprotein cholesterol levels and insulin sensitivity compared with the vehicle
      fed control. Kaempferol also reduced plasma triglyceride concentrations and did
      not cause liver steatosis, a common side effect of potent LXR activation. In
      immunoblotting analysis, kaempferol reduced the nuclear accumulation of sterol
      regulatory element-binding protein-1 (SREBP-1). Our results show that the
      suppression of SREBP-1 activity and the selectivity for LXR-beta over LXR-alpha
      by kaempferol contribute to the reductions of plasma and hepatic triglyceride
      concentrations in mice fed kaempferol. They also suggest that kaempferol
      activates LXR-beta and suppresses SREBP-1 to enhance symptoms in metabolic
      syndrome.

PMID- 25959374
TI  - Folic acid administration inhibits amyloid beta-peptide accumulation in APP/PS1
      transgenic mice.
AB  - Alzheimer's disease (AD) is associated with malnutrition, altered one-carbon
      metabolism and increased hippocampal amyloid-beta peptide (Abeta) accumulation.
      Aberrant DNA methylation may be an epigenetic mechanism that underlies AD
      pathogenesis. We hypothesized that folic acid acts through an epigenetic gene
      silencing mechanism to lower Abeta levels in the APP/PS1 transgenic mouse model
      of AD. APP/PS1 mice were fed either folate-deficient or control diets and gavaged
      daily with 120 MUg/kg folic acid, 13.3mg/kg S-adenosylmethionine (SAM) or both.
      Examination of the mice after 60 days of treatment showed that serum folate
      concentration increased with intake of folic acid but not SAM. Folate deficiency
      lowered endogenous SAM concentration, whereas neither intervention altered S
      adenosylhomocysteine concentration. DNA methyltransferase (DNMT) activity
      increased with intake of folic acid raised DNMT activity in folate-deficient
      mice. DNA methylation rate was stimulated by folic acid in the amyloid precursor
      protein (APP) promoter and in the presenilin 1 (PS1) promoter. Folate deficiency
      elevated hippocampal APP, PS1 and Abeta protein levels, and these rises were
      prevented by folic acid. In conclusion, these findings are consistent with a
      mechanism in which folic acid increases methylation potential and DNMT activity,
      modifies DNA methylation and ultimately decreases APP, PS1 and Abeta protein
      levels.

PMID- 25959376
TI  - Vitamin D3 levels and bone mineral density in patients with psoriasis and/or
      psoriatic arthritis.
AB  - Limited data are available on the vitamin D3 status and bone mineral density
      (BMD) of patients with psoriasis or with psoriatic arthritis. Our study intended
      to explore possible correlations between vitamin D status and BMD, as well as
      among these parameters and the features of the underlying disorder. Seventy-two
      patients with psoriasis/or psoriatic arthritis (female : male ratio, 40:32; mean
      age, 58.5 +/- 11.6 years; mean duration of follow up, 142.7 +/- 147.7 months)
      participated in the study. We evaluated the characteristic clinical features of
      the underlying disease, performed bone densitometry of the lumbar spine and the
      hip region, measured the serum vitamin 25(OH)D3 levels of the patients, and
      undertook the statistical analysis of the relationships between the clinical and
      the laboratory parameters. The proportion of patients with a low BMD value did
      not exceed that seen in the general population. We found an inverse correlation
      between the serum level of vitamin 25(OH)D3 and body mass index, as well as
      between the former and the severity of skin involvement. Furthermore, the
      activity of psoriatic arthritis was significantly higher in patients with
      inadequate vitamin D3 status. In patients with psoriatic arthritis, BMD
      significantly exceeded the values measured in patients suffering from psoriatic
      skin lesions only. Our findings suggest the importance of evaluating the vitamin
      D3 status and screening for comorbid conditions in patients with psoriasis or
      psoriatic arthritis. This appears justified, in particular, due to the possible
      role of hypovitaminosis D3 in provoking the development of skin lesions and joint
      symptoms. 

PMID- 25959378
TI  - Protein profiles of Escherichia coli and Staphylococcus warneri are altered by
      photosensitization with cationic porphyrins.
AB  - Oxidative stress induced by photodynamic treatment of microbial cells causes
      irreversible damages to vital cellular components such as proteins. Photodynamic
      inactivation (PDI) of bacteria, a promising therapeutic approach for the
      treatment of superficial and localized skin and oral infections, can be achieved
      by exciting a photosensitizing agent with visible light in an oxygenated
      environment. Although some studies have addressed the oxidative alterations of
      PDI in bacterial proteins, the present study is the first to compare the
      electrophoretic profiles of proteins of Gram-positive and Gram-negative bacteria,
      having two structurally different porphyrins, with different kinetics of
      photoinactivation. The cationic porphyrins 5,10,15-tris(1-methylpyridinium-4-yl)
      20-(pentafluorophenyl)porphyrin tri-iodide (Tri-Py(+)-Me-PF) and 5,10,15,20
      tetrakis(1-methylpyridinium-4-yl)porphyrin tetra-iodide (Tetra-Py(+)-Me) were
      used to photosensitize Escherichia coli and Staphylococcus warneri upon white
      light irradiation at an irradiance of 4.0 mW cm(-2). After different
      photosensitization periods, proteins were extracted from bacteria and analyzed
      using one-dimensional SDS-PAGE. Apparent molecular weights and band intensities
      were determined after an irradiation period corresponding to a reduction of 4
      log10 in cell viability. After photodynamic treatment, there was a general loss
      of bacterial proteins, assigned to large-scale protein degradation. Protein loss
      was more pronounced after PDI with Tri-Py(+)-Me-PF in both bacteria. There was
      also an increase in the concentration of some proteins as well as an increase in
      the molecular weight of other proteins. We show that proteins of E. coli and S.
      warneri are important targets of PDI. Although there is an attempt of cellular
      response to the PDI-induced damage by overexpression of a limited number of
      proteins, the damage is lethal. Our results show that changes occurring in the
      protein pattern during photodynamic treatment are different with the two
      photosensitizers, which helps to explain the different inactivation kinetics of
      the two bacteria. SDS-PAGE is a rational approach to assign the type of cellular
      response to stress that is being induced in the cells. 

PMID- 25959377
TI  - Early adenosine release contributes to hypoxia-induced disruption of stimulus
      induced sharp wave-ripple complexes in rat hippocampal area CA3.
AB  - We investigated the effects of hypoxia on sharp wave-ripple complex (SPW-R)
      activity and recurrent epileptiform discharges in rat hippocampal slices, and the
      mechanisms underlying block of this activity. Oxygen levels were measured using
      Clark-style oxygen sensor microelectrodes. In contrast to recurrent epileptiform
      discharges, oxygen consumption was negligible during SPW-R activity. These
      network activities were reversibly blocked when oxygen levels were reduced to 20%
      or less for 3 min. The prolongation of hypoxic periods to 6 min caused reversible
      block of SPW-Rs during 20% oxygen and irreversible block when 0% oxygen (anoxia)
      was applied. In contrast, recurrent epileptiform discharges were more resistant
      to prolonged anoxia and almost fully recovered after 6 min of anoxia. SPW-Rs were
      unaffected by the application of 1-butyl-3-(4-methylphenylsulfonyl) urea, a
      blocker of KATP channels, but they were blocked by activation of adenosine A1
      receptors. In support of a modulatory function of adenosine, the amplitude and
      incidence of SPW-Rs were increased during application of the A1 receptor
      antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Interestingly, hypoxia
      decreased the frequency of miniature excitatory post-synaptic currents in CA3
      pyramidal cells, an effect that was converted into increased frequency by the
      adenosine A1 agonist DPCPX. In addition, DPCPX also delayed the onset of hypoxia
      mediated block of SPW-Rs. Our data suggest that early adenosine release during
      hypoxia induces a decrease in pre-synaptic glutamate release and that both might
      contribute to transient block of SPW-Rs during hypoxia/anoxia in area CA3. 

PMID- 25959379
TI  - Temperature-dependent acute toxicity of methomyl pesticide on larvae of 3 Asian
      amphibian species.
AB  - Relative to other animal taxa, ecotoxicological studies on amphibians are scarce,
      even though amphibians are experiencing global declines and pollution has been
      identified as an important threat. Agricultural lands provide important habitats
      for many amphibians, but often these lands are contaminated with pesticides. The
      authors determined the acute toxicity, in terms of 96-h median lethal
      concentrations, of the carbamate pesticide methomyl on larvae of 3 Asian
      amphibian species, the Asian common toad (Duttaphrynus melanostictus), the brown
      tree frog (Polypedates megacephalus), and the marbled pygmy frog (Microhyla
      pulchra), at 5 different temperatures (15  degrees C, 20  degrees C, 25  degrees
      C, 30  degrees C, and 35  degrees C) to examine the relationships between
      temperature and toxicity. Significant interspecific variation in methomyl
      sensitivity and 2 distinct patterns of temperature-dependent toxicity were found.
      Because high proportions of malformation among the surviving tadpoles were
      observed, a further test was carried out on the tree frog to determine effect
      concentrations using malformation as the endpoint. Concentrations as low as 1.4%
      of the corresponding 96-h median lethal concentrations at 25  degrees C were
      sufficient to cause malformation in 50% of the test population. As the toxicity
      of pesticides may be significantly amplified at higher temperatures, temperature
      effects should not be overlooked in ecotoxicological studies and derivation of
      safety limits in environmental risk assessment and management.

PMID- 25959382
TI  - Reduction of ochratoxin A in dry-cured meat products using gamma-irradiation.
AB  - This study investigated the efficiency of gamma (gamma)-irradiation in the
      reduction of ochratoxin A (OTA) present in dry-cured meat products prepared from
      intentionally contaminated raw materials from OTA-treated pigs. OTA
      concentrations determined in the samples (n = 24) ranged from 25.8 MUg kg(-1) in
      bacon to 17.8 MUg kg(-1) in smoked ham. After gamma-irradiation at doses of 3, 7
      and 10 kGy (i.e. the doses used in the food industry), a dose-depended OTA
      reduction was observed; however, it was not statistically significant. The mean
      OTA reduction achieved with 3-, 7- and 10-kGy gamma-doses was approximated to
      8.5%, 13.9% and 22.5%, respectively. The storage of irradiated samples (1 month,
      4 degrees C) did not significantly affect OTA levels. Based on the correlation
      between the OTA reduction level and basic chemical composition of dry-cured meat
      samples, OTA reduction may be linked to the samples' fat content. The results
      indicate that gamma-irradiation can reduce OTA levels in dry-cured meat products,
      but only to a limited extent due to the complexity of the matrix.

PMID- 25959380
TI  - GLP-1 receptor agonists: Nonglycemic clinical effects in weight loss and beyond.
AB  - OBJECTIVE: Glucagon-like peptide-1 (GLP-1) receptor agonists are indicated for
      treatment of type 2 diabetes since they mimic the actions of native GLP-1 on
      pancreatic islet cells, stimulating insulin release, while inhibiting glucagon
      release, in a glucose-dependent manner. The observation of weight loss has led to
      exploration of their potential as antiobesity agents, with liraglutide 3.0 mg
      day(-1) approved for weight management in the US on December 23, 2014, and in the
      EU on March 23, 2015. This review examines the potential nonglycemic effects of
      GLP-1 receptor agonists. METHODS: A literature search was conducted to identify
      preclinical and clinical evidence on nonglycemic effects of GLP-1 receptor
      agonists. RESULTS: GLP-1 receptors are distributed widely in a number of tissues
      in humans, and their effects are not limited to the well-recognized effects on
      glycemia. Nonglycemic effects include weight loss, which is perhaps the most
      widely recognized nonglycemic effect. In addition, effects on the cardiovascular,
      neurologic, and renal systems and on taste perception may occur independently of
      weight loss. CONCLUSIONS: GLP-1 receptor agonists may provide other nonglycemic
      clinical effects besides weight loss. Understanding these effects is important
      for prescribers in using GLP-1 receptor agonists for diabetic patients, but also
      if approved for chronic weight management.

PMID- 25959381
TI  - Experimental acute lung injury induces multi-organ epigenetic modifications in
      key angiogenic genes implicated in sepsis-associated endothelial dysfunction.
AB  - INTRODUCTION: The Tie2/angiopoietin (Tie2/Ang) and vascular endothelial growth
      factor receptor-ligand systems (VEGFR/VEGF) are recognized to play important
      roles in the regulation of microvascular endothelial function. Downregulation of
      these genes during sepsis has been implicated in the pathogenesis of sepsis
      related microvascular leak and multiple organ dysfunction syndrome. Mechanisms
      responsible for dysregulation of angiogenic genes in sepsis are poorly defined.
      METHODS: Western blot, reverse transcription-polymerase chain reaction, and
      multiplex chromatin immunoprecipitation platform (Matrix ChIP) were used to
      investigate serum albumin leak, changes in gene expression, and associated
      epigenetic alterations in a murine model of acute lung injury-induced sepsis (ALI
      sepsis). RESULTS: Experimental ALI-sepsis induced microvascular leak and
      downregulation of expression of Angpt1 (Ang1), Tek (Tie2), and Kdr (Vegfr2 or Flk
      1) genes in the lung, kidney, and liver. These changes correlate with a decrease
      in RNA polymerase II density at these genes, and the greatest response was
      observed in the lung. ALI-sepsis reduced levels of transcription-permissive
      histone H3 lysine acetylation (H3KAc) at these loci in all examined tissues.
      Decreases in permissive H3K4m3 and H3Km2 marks were detected only in the lung. In
      contrast, only minimal alterations in transcription-repressive histone
      modifications (H3K27m3, H3K9m2, H3K9m3, and H4K20m3) were observed in all
      tissues. CONCLUSIONS: Our results demonstrate that decreases in transcription
      permissive, but not increases in transcription-repressive, histone modifications
      at Angpt1, Tek, and Kdr are a systemic, rather than a lung-restricted, response,
      involving key end-organs in experimental ALI-sepsis. Given that ventilator
      associated pneumonia is a major cause of sepsis in critically ill patients,
      elucidation of mechanisms mediating epigenetic alterations during sepsis provides
      fundamental new insights into the pathogenesis of sepsis-induced microvascular
      leak and subsequent end-organ injury/dysfunction.

PMID- 25959383
TI  - Photo-triggered transformation from vesicles to branched nanotubes fabricated by
      a cholesterol-appended cyanostilbene.
AB  - Cholesterol-appended cyanostilbene was synthesized, which could self-assemble
      into vesicles accompanied by a aggregation-induced emission effect. Under UV
      light irradiation, the vesicles gradually merged together to form branched
      nanotubes. The self-assembly and disassembly processes could be utilized in the
      quantitative analysis of external stimulus, which were demonstrated by H2O2
      selective sensing. 

PMID- 25959384
TI  - The impact of mast cells on cardiovascular diseases.
AB  - Mast cells comprise an innate immune cell population, which accumulates in
      tissues proximal to the outside environment and, upon activation, augments the
      progression of immunological reactions through the release and diffusion of
      either pre-formed or newly generated mediators. The released products of mast
      cells include histamine, proteases, as well as a variety of cytokines, chemokines
      and growth factors, which act on the surrounding microenvironment thereby shaping
      the immune responses triggered in various diseased states. Mast cells have also
      been detected in the arterial wall and are implicated in the onset and
      progression of numerous cardiovascular diseases. Notably, modulation of distinct
      mast cell actions using genetic and pharmacological approaches highlights the
      crucial role of this cell type in cardiovascular syndromes. The acquired evidence
      renders mast cells and their mediators as potential prognostic markers and
      therapeutic targets in a broad spectrum of pathophysiological conditions related
      to cardiovascular diseases. 

PMID- 25959385
TI  - Poly(I:C) induced microRNA-146a regulates epithelial barrier and secretion of
      proinflammatory cytokines in human nasal epithelial cells.
AB  - Human nasal epithelial cells (HNECs) are important in the tight junctional
      barrier and innate immune defense protecting against pathogens invading via Toll
      like receptors (TLRs). MicroRNAs (miRNAs) regulate expression of tight junctions
      as direct or indirect targeting genes and maintain the barrier function. However,
      the roles of miRNAs in the epithelial barrier of HNECs via TLRs remain unknown.
      In the present study, to investigate the effects of miRNAs on the epithelial
      barrier of HNECs via TLRs, primary cultured HNECs transfected with human
      telomerase reverse transcriptase (hTERT-HNECs), were treated with the TLR3 ligand
      poly(I:C) and miRNA array analysis was performed. In the miRNA array of the cells
      treated with poly(I:C), upregulation of miR-187, -146a, -574, -4274, -4433, -4455
      and -4750, and downregulation of miR-4785 by more than twofold compared to the
      control were observed. When control HNECs were treated with mimics and inhibitors
      of these miRNAs, an miR-146a mimic induced expression of tight junction proteins
      claudin-1, occludin and JAM-A together with an increase of the epithelial barrier
      function. The poly(I:C)-induced miR-146a was regulated via the distinct TLR3
      mediated signal pathways PI3K, JNK and NF-kappaB. Furthermore, the miR-146a mimic
      prevented downregulation of claudin-1 and JAM-A and the secretion of
      proinflammatory cytokines IL-8 and TNF-alpha induced by poly(I:C) by targeting
      TRAF6. These findings indicate that, in HNECs, miRNA-146a plays crucial roles in
      maintenance of the tight junction barrier and innate immune defense protecting
      against invading pathogens. 

PMID- 25959387
TI  - Chloroquine-based hybrid molecules as promising novel chemotherapeutic agents.
AB  - Chloroquine (CQ) has a broad spectrum of pharmacological activities including
      anticancer and anti-inflammatory, in addition to its well-known antimalarial
      activity. This very useful property of CQ may be rendered through a variety of
      different molecular and cellular mechanisms, including the induction of
      apoptosis, necrosis and lysosomal dysfunction. CQ alone may not be as effective
      as many well-known anticancer drugs; however, it often shows synergisticts when
      combined with other anticancer agents, without causing substantial ill-effects.
      To increase its pharmacological activity, scientists synthesized many different
      chloroquine derivatives by a repositioning approach, some of which show higher
      activities than the parental CQ. To further improve anticancer activity,
      medicinal chemists have recently been focusing on generating CQ hybrid molecules
      by joining, directly or through a linker, 4-aminoquinoline and other
      pharmacologically active phamarcophore(s). Indeed, some CQ hybrid molecules
      substantially improved anticancer activity while maintaining desirable CQ
      property, providing an excellent opportunity of developing effective and safe
      novel anticancer agents. Since the approach of developing CQ hybrid molecules has
      advanced much more in the antimalarial drug research, it can provide an excellent
      template for anticancer drug development. This review provides an overview of CQ
      based hybrid molecules by focusing on: (1) the potential advantage of the hybrid
      approach in developing effective and safe anticancer agents; (2) what we can
      learn from the CQ hybrid approach used in the development of effective
      antimalarial agents; and (3) CQ hybrid molecules as potential anticancer agents
      in different categories classified based on their chemical compositions. 

PMID- 25959388
TI  - Basophils in inflammation.
AB  - Basophils are functionally closely related to mast cells. Both cell types express
      the high-affinity IgE receptor (FcepsilonRI) and rapidly release preformed
      mediator from intracellular stores upon IgE-mediated activation. However, in
      contrast to mast cells basophils finish their maturation in the bone marrow and
      have a lifespan of only 2-3 days. Basophil numbers increase in response to IL-3
      or TSLP and migrate into tissues to promote type 2 immune responses. Here we
      review recent advances regarding the pro- and anti-inflammatory functions of
      basophils in murine models and human allergic inflammation of the skin, lung and
      intestine. 

PMID- 25959389
TI  - Stencil nano lithography based on a nanoscale polymer shadow mask: towards
      organic nanoelectronics.
AB  - A stencil lithography technique has been developed to fabricate organic-material
      based electronic devices with sub-micron resolution. Suspended
      polymethylmethacrylate (PMMA) membranes were used as shadow masks for defining
      organic channels and top electrodes. Arrays of pentacene field effect transistors
      (FETs) with various channel lengths from 50 MUm down to 500 nm were successfully
      produced from the same batch using this technique. Electrical transport
      measurements showed that the electrical contacts of all devices were stable and
      the normalized contact resistances were much lower than previously studied
      organic FETs. Scaling effects, originating from the bulk space charge current,
      were investigated by analyzing the channel-length-dependent mobility and
      hysteresis behaviors. This novel lithography method provides a reliable means for
      studying the fundamental transport properties of organic materials at the
      nanoscale as well as enabling potential applications requiring the fabrication of
      integrated organic nanoelectronic devices. 

PMID- 25959390
TI  - A qualitative study into the impact of fasting within a large tertiary hospital
      in Australia--the patients' perspective.
AB  - AIMS AND OBJECTIVES: This qualitative study aims to explore the physical and
      emotional impact of fasting from the patients' perspective. BACKGROUND: Fasting
      patients in hospital is common practice and generally viewed as necessary for
      symptom management or for safety of healthcare provision. Negative impacts of
      repeated or prolonged fasting on nutritional status have been well researched,
      but little is documented as to how fasting impacts an individual patient's
      psyche. DESIGN: Qualitative descriptive design within a tertiary hospital in
      Sydney, Australia. METHODS: Twelve patients having had prolonged periods of
      continuous or intermittent fasting were invited to participate in a semi
      structured interview between January-September 2012. Questions for interview
      explored each patient's experience of fasting, including physical and emotional
      impacts, interpretation of communication regarding fasting and the process of
      recommencing on fluids or foods. An inductive thematic analysis approach was
      used. RESULTS: Analyses showed six main themes: physical impacts; emotional
      impacts; food as structure; nil by mouth as jargon; fear of food re-introduction;
      and dissatisfaction regarding unnecessary fasting. Overwhelmingly, thirst was
      reported as the worst physical effect of fasting. In the first few days of
      fasting, patients became emotionally fixated on food. This quickly dissipated
      leading to a lack of appetite and fear of starting to eat again. CONCLUSIONS:
      Discomfort experienced by patients coupled with lack of appetite resulting from
      prolonged fasting and difficulty with food re-introduction strengthens the
      argument for reducing fasting times in hospital. When patients are fasted, proper
      hydration and establishing alternate routes of medication administration should
      be a priority. RELEVANCE TO CLINICAL PRACTICE: It is well recognised that fasting
      for prolonged periods is detrimental to health outcomes, but this study also
      shows the distress that fasting can cause. Inadequate hospital systems and out
      dated practices need to be replaced with evidence-based, patient-centred
      governance, addressing the physical, emotional and psychosocial impact of
      fasting.

PMID- 25959386
TI  - Mast cells in airway diseases and interstitial lung disease.
AB  - Mast cells are major effector cells of inflammation and there is strong evidence
      that mast cells play a significant role in asthma pathophysiology. There is also
      a growing body of evidence that mast cells contribute to other inflammatory and
      fibrotic lung diseases such as chronic obstructive pulmonary disease and
      idiopathic pulmonary fibrosis. This review discusses the role that mast cells
      play in airway diseases and highlights how mast cell microlocalisation within
      specific lung compartments and their cellular interactions are likely to be
      critical for their effector function in disease. 

PMID- 25959391
TI  - Developmental trajectories as autism phenotypes.
AB  - Numerous studies of Autism Spectrum Disorder have attempted to link behavioral
      phenotypes to genetic findings. Reliance on cross-sectional behavioral data in
      samples that span wide age ranges may have limited this endeavor because ASD
      behaviors are not static within individuals across development. This study uses
      quantitative methods to describe specific aspects of changes in autism-related
      and more general behaviors in order to yield trajectories that could be used in
      place of single time-point data as behavioral phenotypes in neurobiological
      studies of both Autism Spectrum Disorders and overlapping conditions. Building on
      previous analyses, we examined trajectories of parent-reported social
      communication deficits, social adaptive functioning, and two types of repetitive
      behaviors, repetitive sensory motor (RSM) behaviors and insistence on sameness
      (IS) behaviors, in a relatively large sample of participants referred for
      possible autism at age 2 years and followed into young adulthood (n=85). A
      strength of this sample was the diverse range of outcomes, including young adults
      with intellectual disability and persistent autism related difficulties, those
      with IQs in the borderline or average range who continued to experience
      functional impairment related to Autism Spectrum Disorders, and a small group of
      young adults (n=8) with IQs in the average range who were judged to be
      functioning socially and adaptively at age-appropriate levels at age 19 years,
      despite a previous childhood diagnosis of autism.

PMID- 25959392
TI  - Iron deposition in the gray matter in patients with relapse-remitting multiple
      sclerosis: A longitudinal study using three-dimensional (3D)-enhanced T2*
      weighted angiography (ESWAN).
AB  - PURPOSE: To investigate the relationship between the iron content by magnetic
      resonance imaging (MRI) and clinic correlation in patients with relapse-remitting
      multiple sclerosis (RRMS) over a two-year period. METHODS: Thirty RRMS patients
      and 30 healthy control subjects were examined twice, two years apart, by
      undergoing brain conventional MRI and three-dimensional (3D)-enhanced T2*
      weighted angiography (ESWAN) sequences at 3.0T. Quantitative differences in iron
      content in deep gray matter (GM) nuclei and precentral gyrus GM between patients
      and control subjects with repeated-measures the mean phase values (MPVs) for
      ESWAN-filtered phase images. Spearman's rank correlation coefficient analysis was
      used to evaluate correlations of the MPVs, both 2-year-difference and single-time
      measurements, to disease duration, expanded disability status scale (EDSS) and
      times of recurrence. RESULTS: The RRMS patients had higher GM iron concentration
      than that of the healthy control subjects in both single-time measurements, but
      only the substantia nigra (SN), and the precentral gyrus GM (PGM) showed a
      significant statistical difference (p<0.05). Using the paired samples t test, we
      found that there were significant differences in two-year-difference measurements
      of the MPVs in the putamen (PUT), the globus pallidus (GP), the head of the
      caudate nucleus (HCN), the thalamus (THA), SN, the red nucleus (RN), the dentate
      nucleus (DN) and PGM, especially in SN (t=2.92, p=0.007) in RRMS patients. The
      MPVs of the PUT, GP, HCN, THA, SN, RN, DN and PGM for the subgroup with RRMS
      patients in times of recurrence less than twice were similar to the healthy
      controls. There was no significant difference in all regions of interests (ROIs).
      However, there were significant differences in all ROIs except THA and GP for the
      other subgroup with RRMS patients in times of recurrence more than and equal to
      twice. Spearman's rank correlation coefficient analysis showed there were
      significant negative correlations between disease duration and the MPVs in the
      HCN (r=-0.516, p=0.004), DN (r=-0.468, p=0.009) and PGM (r=-0.84, p=0). However,
      no correlations were found between the EDSS scores and the MPVs. CONCLUSIONS:
      Iron content in the GM can be measurable using MRI and our results confirmed that
      iron concentration was increasing in the GM of MS patients during two-year period
      compared to healthy controls. Furthermore, this study had also shown significant
      and substantial correlation of iron concentration with disease severity.

PMID- 25959394
TI  - ERp44 Exerts Redox-Dependent Control of Blood Pressure at the ER.
AB  - Blood pressure maintenance is vital for systemic homeostasis, and angiotensin II
      is a critical regulator. The upstream mechanisms that regulate angiotensin II are
      not completely understood. Here, we show that angiotensin II is regulated by
      ERp44, a factor involved in disulfide bond formation in the ER. In mice, genetic
      loss of ERp44 destabilizes angiotensin II and causes hypotension. We show that
      ERp44 forms a mixed disulfide bond with ERAP1, an aminopeptidase that cleaves
      angiotensin II. ERp44 controls the release of ERAP1 in a redox-dependent manner
      to control blood pressure. Additionally, we found that systemic inflammation
      triggers ERAP1 retention in the ER to inhibit hypotension. These findings suggest
      that the ER redox state calibrates serum angiotensin II levels via regulation of
      the ERp44-ERAP1 complex. Our results reveal a link between ER function and
      normotension and implicate the ER redox state as a potential risk factor in the
      development of cardiovascular disease.

PMID- 25959393
TI  - The Histone Chaperones FACT and Spt6 Restrict H2A.Z from Intragenic Locations.
AB  - H2A.Z is a highly conserved histone variant involved in several key nuclear
      processes. It is incorporated into promoters by SWR-C-related chromatin
      remodeling complexes, but whether it is also actively excluded from non-promoter
      regions is not clear. Here we provide genomic and biochemical evidence that the
      RNA polymerase II (RNA Pol II) elongation-associated histone chaperones FACT and
      Spt6 both contribute to restricting H2A.Z from intragenic regions. In the absence
      of FACT or Spt6, the lack of efficient nucleosome reassembly coupled to pervasive
      incorporation of H2A.Z by mislocalized SWR-C alters chromatin composition and
      contributes to cryptic initiation. Therefore, chaperone-mediated H2A.Z
      confinement is crucial for restricting the chromatin signature of gene promoters
      that otherwise may license or promote cryptic transcription.

PMID- 25959395
TI  - Mechanism of Transcription Termination by RNA Polymerase III Utilizes a Non
      template Strand Sequence-Specific Signal Element.
AB  - Understanding the mechanism of transcription termination by a eukaryotic RNA
      polymerase (RNAP) has been limited by lack of a characterizable intermediate that
      reflects transition from an elongation complex to a true termination event. While
      other multisubunit RNAPs require multipartite cis-signals and/or ancillary
      factors to mediate pausing and release of the nascent transcript from the
      clutches of these enzymes, RNAP III does so with precision and efficiency on a
      simple oligo(dT) tract, independent of other cis-elements or trans-factors. We
      report an RNAP III pre-termination complex that reveals termination mechanisms
      controlled by sequence-specific elements in the non-template strand. Furthermore,
      the TFIIF-like RNAP III subunit C37 is required for this function of the non
      template strand signal. The results reveal the RNAP III terminator as an
      information-rich control element. While the template strand promotes
      destabilization via a weak oligo(rU:dA) hybrid, the non-template strand provides
      distinct sequence-specific destabilizing information through interactions with
      the C37 subunit.

PMID- 25959396
TI  - Molecular Basis of Transcription-Coupled Pre-mRNA Capping.
AB  - Capping is the first step in pre-mRNA processing, and the resulting 5'-RNA cap is
      required for mRNA splicing, export, translation, and stability. Capping is
      functionally coupled to transcription by RNA polymerase (Pol) II, but the
      coupling mechanism remains unclear. We show that efficient binding of the capping
      enzyme (CE) to transcribing, phosphorylated yeast Pol II (Pol IIp) requires
      nascent RNA with an unprocessed 5'-triphosphate end. The transcribing Pol IIp-CE
      complex catalyzes the first two steps of capping, and its analysis by mass
      spectrometry, cryo-electron microscopy, and protein crosslinking revealed the
      molecular basis for transcription-coupled pre-mRNA capping. CE docks to the Pol
      II wall and spans the end of the RNA exit tunnel to position the CE active sites
      for sequential binding of the exiting RNA 5' end. Thus, the RNA 5' end triggers
      its own capping when it emerges from Pol II, to ensure seamless RNA protection
      from 5'-exonucleases during early transcription.

PMID- 25959397
TI  - LOXL2 Oxidizes Methylated TAF10 and Controls TFIID-Dependent Genes during Neural
      Progenitor Differentiation.
AB  - Protein function is often regulated and controlled by posttranslational
      modifications, such as oxidation. Although oxidation has been mainly considered
      to be uncontrolled and nonenzymatic, many enzymatic oxidations occur on enzyme
      selected lysine residues; for instance, LOXL2 oxidizes lysines by converting the
      epsilon-amino groups into aldehyde groups. Using an unbiased proteomic approach,
      we have identified methylated TAF10, a member of the TFIID complex, as a LOXL2
      substrate. LOXL2 oxidation of TAF10 induces its release from its promoters,
      leading to a block in TFIID-dependent gene transcription. In embryonic stem
      cells, this results in the inactivation of the pluripotency genes and loss of the
      pluripotent capacity. During zebrafish development, the absence of LOXL2 resulted
      in the aberrant overexpression of the neural progenitor gene Sox2 and impaired
      neural differentiation. Thus, lysine oxidation of the transcription factor TAF10
      is a controlled protein modification and demonstrates a role for protein
      oxidation in regulating pluripotency genes. 

PMID- 25959398
TI  - Phosphorylation-Dependent Enhancement of Rad53 Kinase Activity through the INO80
      Chromatin Remodeling Complex.
AB  - ATP-dependent chromatin remodeling complexes such as INO80 have been implicated
      in checkpoint regulation in response to DNA damage. However, how chromatin
      remodeling complexes regulate DNA damage checkpoints remain unclear. Here, we
      identified a mechanism of regulating checkpoint effector kinase Rad53 through a
      direct interaction with the INO80 chromatin remodeling complex. Rad53 is a key
      checkpoint kinase downstream of Mec1. Mec1/Tel1 phosphorylates the Ies4 subunit
      of the INO80 complex in response to DNA damage. We find that the phosphorylated
      Ies4 binds to the N-terminal FHA domain of Rad53. In vitro, INO80 can activate
      Rad53 kinase activity in an Ies4-phosphorylation-dependent manner in the absence
      of known activators such as Rad9. In vivo, Ies4 and Rad9 function synergistically
      to activate Rad53. These findings establish a direct connection between ATP
      dependent chromatin remodeling complexes and checkpoint regulation. 

PMID- 25959400
TI  - Chip-based generation of carbon nanodots via electrochemical oxidation of screen
      printed carbon electrodes and the applications for efficient cell imaging and
      electrochemiluminescence enhancement.
AB  - A portable lab-on-a-chip methodology to generate ionic liquid-functionalized
      carbon nanodots (CNDs) was developed via electrochemical oxidation of screen
      printed carbon electrodes. The CNDs can be successfully applied for efficient
      cell imaging and solid-state electrochemiluminescence sensor fabrication on the
      paper-based chips. 

PMID- 25959399
TI  - Using the unfolding case study in midwifery education.
AB  - One of the challenges in teaching clinicians is helping health care provider
      students, including midwives, develop the critical thinking and clinical decision
      making skills needed for various situations encountered in practice. Health care
      provider students need to master the required core knowledge and skills but also
      need to assess, analyze, judge, decide on action, act, and evaluate their
      actions. Lecture-heavy classroom teaching, which is usually delivered separately
      from clinical experiences in health care education, focuses on knowledge
      acquisition, often leaving knowledge application to trial and error. Case studies
      are commonly used by faculty with a problem-based learning approach, which is
      more analytic but sometimes static. The unfolding case study presents students
      with a patient scenario that changes over time and allows for discussion; lecture
      points as needed; and decision making as the situation or condition changes,
      reflecting what happens in real-life clinical practice. The use of the unfolding
      case study moves health care provider education from fact-based lecturing to
      situation-based discussion and decision making as a person's condition or
      situation changes. Use of the unfolding case facilitates collaborative learning,
      covers necessary content, and assists students to think beyond the facts and use
      their clinical imagination. Unfolding case studies require students to begin to
      grasp the nature of a clinical situation and adjust interventions as the clinical
      situation unfolds. Steps in developing and using an unfolding case study for
      midwifery students are presented, including 2 examples. This article is part of a
      special series of articles that address midwifery innovations in clinical
      practice, education, interprofessional collaboration, health policy, and global
      health. 

PMID- 25959401
TI  - [Personalised medicine applied to mental health: Precision psychiatry].

PMID- 25959402
TI  - Oral health promotion interventions during pregnancy: a systematic review.
AB  - OBJECTIVES: Maternal oral disease during pregnancy is a significant public health
      issue due to its prevalence and lifecourse connections with adverse
      pregnancy/birth outcomes, early childhood caries, and chronic diseases. Although
      both medical and dental professional organizations have discipline-specific and
      co-endorsed guidelines, whether interventions exist that translate oral health
      evidence into practice remains unknown. Thus, we conducted a systematic review to
      examine the range, scope and impact of existing oral health promotion
      interventions during pregnancy. METHODS: Search terms related to oral health,
      health promotion, and pregnancy produced 7754 articles published before March
      2013 from five search engines. INCLUSION CRITERIA: (i) intervention-based; (ii)
      quasi-experimental, experimental, or pretest/post-test design; (iii) pregnant
      women participants; (iv) outcomes including oral health knowledge, attitudes,
      and/or behaviors; (v) >=5 participants; (vi) peer-review publication; and (vii)
      English language. RESULTS: All interventions (n = 7) were delivered in prenatal
      care settings and focused on education. Modalities varied, including the use of
      oral instruction and audiovisual presentations, in both individual and group
      formats; however, content was directed toward infant oral health. Few studies
      specifically addressed prenatal oral health guidelines. Primary outcomes measured
      included knowledge, beliefs, attitudes, self-efficacy and oral hygiene, and
      health-seeking behaviors. All but one study showed significant improvement in one
      of these outcomes postintervention. CONCLUSIONS: Few oral health interventions
      among pregnant women addressed oral-related symptoms, hygiene behaviors, and
      potential oral-systemic implications specific to mothers. Subsequently, more
      theory- and evidence-based interventions addressing current prenatal oral health
      guidelines using rigorous designs are needed to improve oral and systemic health
      for both women and their offspring.

PMID- 25959403
TI  - Rapid identification of aminoglycoside-induced deafness gene mutations using
      multiplex real-time polymerase chain reaction.
AB  - BACKGROUND: Exposure to aminoglycoside antibiotics can induce ototoxicity in
      genetically susceptible individuals carrying certain mitochondrial DNA (mtDNA)
      mutations (C1494T and A1555G), resulting in hearing loss. So, a rapid diagnostic
      approach is needed to accurately identify subjects carrying such gene mutations.
      METHODS: In the present study, we describe a rapid and reliable four-color, real
      time quantitative polymerase chain reaction (qPCR) assay for simultaneously
      detecting two mtDNA 12S rRNA gene variants, A1555G and C1494T, which are
      prevalent in the Han Chinese population. This multiplex assay incorporates three
      allele-specific TaqMan probes labeled with different fluorophores in a single
      reaction, providing high genotyping accuracy for clinical blood samples. RESULTS:
      Tests with C1494T, A1555G and wild-type DNA exhibited high sensitivity,
      specificity, reproducibility and accuracy of discriminating mutations from wild
      type. CONCLUSIONS: This study shows that this simple and inexpensive method can
      be used for routine molecular diagnostics and potentially for large-scale genetic
      screening.

PMID- 25959404
TI  - Cochlear nerve diameters on multipoint measurements and effects of aging in
      normal-hearing children using 3.0-T magnetic resonance imaging.
AB  - OBJECTIVE: The aim of this study was to determine differences in diameter of
      cochlear nerves (CN) among three measurement points at the midpoint of the
      internal auditory canal (IAC), IAC fundus and cochlear aperture, and to evaluate
      whether nerve size varies with age. METHODS: A total of 336 normal-hearing ears
      of 201 children were assessed, who were underwent 3D-Fiesta sequence scanning of
      inner ear. All subjects were divided into 12 groups at one year interval. The
      diameter measurements of CN were obtained in the midpoint of the IAC, IAC fundus
      and cochlear aperture respectively on the axial and oblique sagittal images of
      3.0-T MRI. SPSS 18.0 statistics software was applied for data analysis, and all
      of the data showed a normal distribution and expressed in x +/- s. RESULTS: The
      diameters of normal-hearing children's CN at the midpoint of the IAC, IAC fundus
      and cochlear aperture were respectively: 1.12 +/- 0.08 mm, 1.05 +/- 0.06 mm, 0.87
      +/- 0.14 mm, and there were significant differences among the three measuring
      points (F = 527.57, p < 0.05). The diameters of the CN had no significant
      difference (p > 0.05) in age groups, gender and sides (p > 0.05), and there was
      no correlation between the diameters of normal children's CN and age (r is 
      0.129, 0.128 and -0.113, respectively). CONCLUSION: The diameters of normal
      hearing children's CN change with different points of the internal auditory
      canal, of which the maximum value is in the midpoint of the IAC, followed by the
      IAC fundus, and the cochlear aperture is at the minimum; moreover the normal size
      doesn't change with age.

PMID- 25959405
TI  - Comparative outcomes of severe obstructive sleep apnea in pediatric patients with
      Trisomy 21.
AB  - OBJECTIVES: To analyze the outcomes of severe obstructive sleep apnea (OSA) in
      pediatric patients with Trisomy 21 compared with non-syndromic patients. METHODS:
      A retrospective chart review was performed for patients with a diagnosis of
      severe obstructive sleep apnea, (defined as, Apnea-Hypopnea index (AHI) of >= 10)
      in a tertiary children's hospital. Data were analyzed for subjective and
      objective outcomes along with perioperative care and health care utilization.
      Patients with Trisomy 21 were compared with non-syndromic patients. RESULTS: A
      total of 230 patients with severe OSA were included in the study. Eighteen of
      these patients had Trisomy 21. Adenotonsillectomy was the most common surgical
      intervention in both groups. There was no statistical difference in the
      preoperative AHI between groups. Post treatment AHI in the Trisomy 21 group
      changed from an average of 26.6 to an average of 11.6 as compared with 24.5 to
      3.6 in the non-syndromic group. The average perioperative hospital stay was 3.8
      days in Trisomy 21 group compared to 1.7 days for the non-syndromic group (p <
      0.001, Mann-Whitney U test). Complete resolution was seen in 35% of the Trisomy
      21 group versus 75% in the non-syndromic group. CONCLUSIONS: A majority of
      Trisomy 21 patients with severe OSA had residual symptoms following surgical
      intervention. There is also an increased risk of post-operative airway
      intervention and increased length of hospital stay in these patients.

PMID- 25959406
TI  - rBTI extends Caenorhabditis elegans lifespan by mimicking calorie restriction.
AB  - Buckwheat trypsin inhibitor (BTI) is a low molecular weight polypeptide extracted
      from buckwheat. This study examined the effects of BTI on the lifespan of
      Caenorhabditis elegans (C. elegans) and investigated the mechanism involved. Our
      results showed that recombinant BTI (rBTI) extended life expectancy by mimicking
      calorie restriction (CR) in C. elegans. rBTI promoted formation of reactive
      oxygen species (ROS) via increasing respiration, induced activities of ROS
      defense enzymes by activating DAF-16, and increased oxidative stress resistance
      and survival rates. The inhibition of ROS signal by antioxidants reduced rBTI
      mediated longevity by up to 65%. Moreover, it was shown that the disruption of
      daf-2 abolished the extension of the lifespan and the increased ROS. Taken
      together, these data indicate that rBTI-mediated longevity mimics CR by down
      regulating insulin/IGF-1 signaling (IIS) pathway, implying that BTI has the
      potential to be a novel anti-aging drug. 

PMID- 25959407
TI  - The role of surface hydrolysis of ferricyanide anions in crystal growth of
      snowflake-shaped alpha-Fe2O3.
AB  - Selective adsorption and surface hydrolysis of [Fe(CN)6](3-) anions on alpha
      Fe2O3 crystals was found to be a crucial process in the formation of a snowflake
      like morphology, and the established mechanism is complementary to the classical
      theories of crystal growth. 

PMID- 25959408
TI  - Effectiveness of a peer-delivered dissonance-based program in reducing eating
      disorder risk factors in high school girls.
AB  - OBJECTIVE: This pilot study investigated the feasibility, acceptability, and
      effectiveness of a peer-led dissonance-based eating disorders (ED)
      prevention/risk factor reduction program with high school girls. METHOD: Ninth
      grade girls (n = 50) received the peer-led program within the school curriculum.
      A quasi-experimental design was used to assess changes in ED risk factors
      preintervention and postintervention compared with waitlist control. Participants
      were followed through 3-month follow-up. RESULTS: Peer-leader adherence to an
      intervention manual tailored for this age group was high. The intervention was
      rated as highly acceptable, with a large proportion of participants reporting
      that they enjoyed the program and learned and applied new information.
      Intervention participants exhibited significantly greater pre-post reductions in
      a majority of risk-factor outcomes compared to waitlist controls. When groups
      were combined to assess program effects over time there were significant pre-post
      reductions in a majority of outcomes that were sustained through 3-month follow
      up. DISCUSSION: This pilot study provides tentative support for the effectiveness
      of using peer leaders to implement an empirically supported ED risk factor
      reduction program in a high school setting. Additional research is needed to
      replicate results in larger, better-controlled trials with longer follow-up.

PMID- 25959409
TI  - Electrophilic Addition to Alkenes: The Relation between Reactivity and Enthalpy
      of Hydrogenation: Regioselectivity is Determined by the Stability of the Two
      Conceivable Products.
AB  - Although electrophilic addition to alkenes has been well studied, some secrets
      still remain. Halogenations, hydrohalogenations, halohydrin formations,
      hydrations, epoxidations, other oxidations, carbene additions, and ozonolyses are
      investigated to elucidate the relation of alkene reactivities with their
      enthalpies of hydrogenation (DeltaHhyd ). For addition of electrophiles to
      unconjugated hydrocarbon alkenes, ln(k) is a linear function of DeltaHhyd , where
      k is the rate constant. Linear correlation coefficients are about 0.98 or
      greater. None of the many previously proposed correlations of ln(k) with the
      properties of alkenes or with linear free-energy relationships match the
      generality and accuracy of the simple linear relationship found herein. A notable
      exception is acid-catalyzed hydration in water or in solvents stabilizing
      relatively stable carbocation intermediates (e.g., tertiary, benzylic, or
      allylic). (13) C NMR chemical shifts of the two alkene carbons also predict
      regioselectivity. These effects have not been noted previously and are operative
      in general, including addition to heteroatom-substituted alkenes. 

PMID- 25959410
TI  - Whole-exome sequencing as a diagnostic tool: current challenges and future
      opportunities.
AB  - Whole-exome sequencing (WES) represents a significant breakthrough in the field
      of human genetics. This technology has largely contributed to the identification
      of new disease-causing genes and is now entering clinical laboratories. WES
      represents a powerful tool for diagnosis and could reduce the 'diagnostic
      odyssey' for many patients. In this review, we present a technical overview of
      WES analysis, variants annotation and interpretation in a clinical setting. We
      evaluate the usefulness of clinical WES in different clinical indications, such
      as rare diseases, cancer and complex diseases. Finally, we discuss the efficacy
      of WES as a diagnostic tool and the impact on patient management. 

PMID- 25959411
TI  - MiR-154-5p regulates osteogenic differentiation of adipose-derived mesenchymal
      stem cells under tensile stress through the Wnt/PCP pathway by targeting Wnt11.
AB  - Mechanical stress is a well-acknowledged positive regulatory factor for
      osteogenic differentiation of adipose- derived mesenchymal stem cells (ADSCs).
      However, the molecular mechanisms associated with micro-RNAs (miRNAs) whereby
      ADSCs respond to mechanical stimuli remain elusive. We investigated the mechanism
      of mechanotransduction from the miRNA perspective in the osteogenic
      differentiation of ADSCs under tensile stress. Microarray analysis showed that
      miR-154-5p was remarkably downregulated when ADSCs were subjected to mechanical
      tension. Bioinformatics analysis with luciferase reporter assays demonstrated
      that Wnt11 3'UTR was a new direct target of miR-154-5p. Under tensile stress,
      lentivirus-mediated gain- or loss-of-function studies revealed that forced
      expression of miR-154-5p inhibited osteogenic differentiation of ADSCs, whereas
      inhibition of endogenous miR-154-5p with its antisense oligonucleotide (ASO-154
      5p) obviously promoted osteogenic differentiation. Furthermore, miR-154-5p
      overexpression decreased activity of the non-canonical Wnt/PCP (RhoA-ROCK)
      pathway, as indicated by lower expression of Wnt11, active RhoA and ROCKII in miR
      154-5p-treated ADSCs. By contrast, miR-154-5p inhibition activated the Wnt/PCP
      signals. Taken together, these results demonstrate that, under tensile stress,
      miR-154-5p negatively regulates ADSCs osteogenic differentiation through the
      Wnt/PCP pathway by directly targeting Wnt11. This novel regulatory pathway
      provides new insights into the molecular mechanism of mechanotransduction in
      osteogenic differentiation of ADSCs. 

PMID- 25959412
TI  - Heparin affects human bone marrow stromal cell fate: Promoting osteogenic and
      reducing adipogenic differentiation and conversion.
AB  - Heparins are broadly used for the prevention and treatment of thrombosis and
      embolism. Yet, osteoporosis is considered to be a severe side effect in up to one
      third of all patients on long-term treatment. However, the mechanisms underlying
      this clinical problem are only partially understood. To investigate if heparin
      affects differentiation of skeletal precursors, we examined the effects of
      heparin on the osteogenic and adipogenic lineage commitment and differentiation
      of primary human bone marrow stromal cells (hBMSCs). Due to the known inverse
      relationship between adipogenesis and osteogenesis and the capacity of pre
      differentiated cells to convert into the respective other lineage, we also
      determined heparin effects on osteogenic conversion and adipogenic
      differentiation/conversion. Interestingly, heparin did not only significantly
      increase mRNA expression and enzyme activity of the osteogenic marker alkaline
      phosphatase (ALP), but it also promoted mineralization during osteogenic
      differentiation and conversion. Furthermore, the mRNA expression of the
      osteogenic marker bone morphogenic protein 4 (BMP4) was enhanced. In addition,
      heparin administration partly prevented adipogenic differentiation and conversion
      demonstrated by reduced lipid droplet formation along with a decreased expression
      of adipogenic markers. Moreover, luciferase reporter assays, inhibitor
      experiments and gene expression analyses revealed that heparin had putative
      permissive effects on osteogenic signaling via the BMP pathway and reduced the
      mRNA expression of the Wnt pathway inhibitors dickkopf 1 (DKK1) and sclerostin
      (SOST). Taken together, our data show a rather supportive than inhibitory effect
      of heparin on osteogenic hBMSC differentiation and conversion in vitro. Further
      studies will have to investigate the net effects of heparin administration on
      bone formation versus bone resorption in vivo to unravel the molecular mechanisms
      of heparin-associated osteoporosis and reconcile conflicting experimental data
      with clinical observations. 

PMID- 25959413
TI  - Multiple roles of tumor necrosis factor-alpha in fracture healing.
AB  - This review presents a summary of basic science evidence examining the influence
      of tumor necrosis factor-alpha (TNF-alpha) on secondary fracture healing.
      Multiple studies suggest that TNF-alpha, in combination with the host reservoir
      of peri-fracture mesenchymal stem cells, is a main determinant in the success of
      bone healing. Disease states associated with poor bone healing commonly have
      inappropriate TNF-alpha responses, which likely contributes to the higher
      incidence of delayed and nonunions in these patient populations. Appreciation of
      TNF-alpha in fracture healing may lead to new therapies to augment recovery and
      reduce the incidence of complications. 

PMID- 25959414
TI  - The epigenetically active small chemical N-methyl pyrrolidone (NMP) prevents
      estrogen depletion induced osteoporosis.
AB  - Currently, there are several treatments for osteoporosis however; they all
      display some sort of limitation and/or side effects making the need for new
      treatments imperative. We have previously demonstrated that NMP is a bioactive
      drug which enhances bone regeneration in vivo and acts as an enhancer of bone
      morphogenetic protein (BMP) in vitro. NMP also inhibits osteoclast
      differentiation and attenuates bone resorption. In the present study, we tested
      NMP as a bromodomain inhibitor and for osteoporosis prevention on ovariectomized
      (OVX) induced rats while treated systemically with NMP. Female Sprague-Dawley
      rats were ovariectomized and weekly NMP treatment was administrated 1 week after
      surgery for 15 weeks. Bone parameters and related serum biomarkers were analyzed.
      15 weeks of NMP treatment decreased ovariectomy-induced gained weight in average
      by 43% and improved bone mineral density (BMD) and bone volume over total volume
      (BV/TV) in rat femur on average by 25% and 41% respectively. Moreover, mineral
      apposition rate and bone biomarkers of bone turnover in the treatment group were
      at similar levels with those of the Sham group. Due to the function of NMP as a
      low affinity bromodomain inhibitor and its mechanism of action involving
      osteoblasts/osteoclasts balance and inhibitory effect on inflammatory cytokines,
      NMP is a promising therapeutic compound for the prevention of osteoporosis.

PMID- 25959415
TI  - Relationships between bone geometry, volumetric bone mineral density and bone
      microarchitecture of the distal radius and tibia with alcohol consumption.
AB  - PURPOSE: Chronic heavy alcohol consumption is associated with bone density loss
      and increased fracture risk, while low levels of alcohol consumption have been
      reported as beneficial in some studies. However, studies relating alcohol
      consumption to bone geometry, volumetric bone mineral density (vBMD) and bone
      microarchitecture, as assessed by high-resolution peripheral quantitative
      computed tomography (HR-pQCT), are lacking. METHODS: Here we report an analysis
      from the Hertfordshire Cohort Study, in which we studied associations between HR
      pQCT measures at the distal radius and tibia and alcohol consumption in 376
      participants (198 men and 178 women) aged 72.1-81.4 years. RESULTS: A total of 30
      (15.2%), 90 (45.5%) and 78 (39.4%) men drank minimal/none (<1 unit/week), low
      (>=1 unit/week and <11 units/week) and moderate/high (>=11 units/week) amounts of
      alcohol respectively. These figures were 74 (41.8%), 80 (45.2%) and 23 (13.0%)
      respectively in women for minimal/none (<1 unit/week), low (>=1 unit/week and <8
      units/week) and moderate/high (>=8 units/week). At the distal radius, after
      adjustment for confounding factors (age, BMI, smoking status, dietary calcium
      intake, physical activity and socioeconomic status and years since menopause and
      HRT use for women), men that drank low alcohol had lower cortical thickness
      (p=0.038), cortical vBMD (p=0.033), and trabecular vBMD (p=0.028) and higher
      trabecular separation (p=0.043) than those that drank none/minimal alcohol.
      Similar differences were shown between minimal/none and moderate/high alcohol
      although these only reached statistical significance for the cortical parameters.
      Interestingly, after similar adjustment, women showed similar differences in the
      trabecular compartment between none/minimal alcohol and low alcohol at the distal
      tibia. However, women that drank moderate/high alcohol had significantly higher
      trabecular vBMD (p=0.007), trabecular thickness (p=0.026), and trabecular number
      (p=0.042) and higher trabecular separation (p=0.026) at the distal radius than
      those that drank low alcohol. CONCLUSIONS: Our results suggest that alcohol
      consumption (low and moderate/high) may have a detrimental impact on bone health
      in men in both the cortical and trabecular compartments at the distal radius with
      similar results in women in the trabecular compartment between none/minimal
      alcohol and low alcohol at the distal tibia suggesting that avoidance of alcohol
      may be beneficial for bone health.

PMID- 25959416
TI  - Impact of prophylactic CpG Oligodeoxynucleotide application on implant-associated
      Staphylococcus aureus bone infection.
AB  - TLR-9 ligand CpG oligodeoxynucleotide type B (CpG ODN) induces a proinflammatory
      environment. We evaluated the effects of a preoperative CpG ODN application in an
      implant-associated Staphylococcus aureus bone infection model by monitoring
      bacterial loads and cytokine and chemokine levels. A total of 95 rats were used
      in four different groups: CpG ODN group (group 1; n=25), non-CpG-ODN group (group
      2; n=25); saline pretreatment (group 3; n=25), and one uninfected group (group 4;
      n=20). A single dose of CpG-ODN was administered to the left tibialis anterior
      muscle 3days prior to surgery and the tibia midshaft was osteotomized, stabilized
      by an intramedullary implant and subsequently contaminated with 10(3) colony
      forming units (CFUs) of S. aureus in groups 1-3. The osteotomy gap in animals of
      group 4 was not contaminated with S. aureus and those animals did not receive any
      pretreatment. CpG ODN administration resulted in significant reduction of the
      bacterial load in tibia tissue homogenate and on the implant surface on day 1
      post-infection compared to non-CpG-ODN pretreatment (p<0.05; p<0.05). Reductions
      in bacterial CFUs, compared to non-treated (saline) controls, were approximately
      67% and 77% for bone tissue homogenates and implants. No bacteria were detected
      in uninfected rats. Early reduction of bacterial CFUs in the tibia was
      accompanied by increased levels of proinflammatory mediators MIP-2, IL-1beta and
      RANTES in bone tissue milieu of the CpG ODN treated group compared to controls.
      At day 42 post-infection, bone marrow tissue of rats pretreated with CpG ODN had
      comparable high bacterial CFU numbers as the non-CpG ODN or saline treated
      groups. Microbiological analysis of implants removed from CpG ODN treated rats
      showed high bacterial growth densities on their surfaces which were not different
      from those observed in controls. In histology, all animals of groups 1-3 showed
      established infected non-unions. Additionally, inflammatory mediator profiles in
      bone marrow homogenates of CpG ODN treated rats resembled those seen in infected
      controls. In this rat model, prophylactic administration of a single dose of CpG
      ODN, resulted in marked reduction of S. aureus load in the infected tibia during
      the initial stage of infection but failed to prevent development of chronic
      infection over time. 

PMID- 25959418
TI  - Measuring the drinking behaviour of individual pigs housed in group using radio
      frequency identification (RFID).
AB  - Changes in the drinking behaviour of pigs may indicate health, welfare or
      productivity problems. Automated monitoring and analysis of drinking behaviour
      could allow problems to be detected, thus improving farm productivity. A high
      frequency radio frequency identification (HF RFID) system was designed to
      register the drinking behaviour of individual pigs. HF RFID antennas were placed
      around four nipple drinkers and connected to a reader via a multiplexer. A total
      of 55 growing-finishing pigs were fitted with radio frequency identification
      (RFID) ear tags, one in each ear. RFID-based drinking visits were created from
      the RFID registrations using a bout criterion and a minimum and maximum duration
      criterion. The HF RFID system was successfully validated by comparing RFID-based
      visits with visual observations and flow meter measurements based on visit
      overlap. Sensitivity was at least 92%, specificity 93%, precision 90% and
      accuracy 93%. RFID-based drinking duration had a high correlation with observed
      drinking duration (R 2=0.88) and water usage (R 2=0.71). The number of
      registrations after applying the visit criteria had an even higher correlation
      with the same two variables (R 2=0.90 and 0.75, respectively). There was also a
      correlation between number of RFID visits and number of observed visits (R
      2=0.84). The system provides good quality information about the drinking
      behaviour of individual pigs. As health or other problems affect the pigs'
      drinking behaviour, analysis of the RFID data could allow problems to be detected
      and signalled to the farmer. This information can help to improve the
      productivity and economics of the farm as well as the health and welfare of the
      pigs. 

PMID- 25959417
TI  - Enzyme replacement for craniofacial skeletal defects and craniosynostosis in
      murine hypophosphatasia.
AB  - Hypophosphatasia (HPP) is an inborn-error-of-metabolism disorder characterized by
      deficient bone and tooth mineralization due to loss-of function mutations in the
      gene (Alpl) encoding tissue-nonspecific alkaline phosphatase (TNAP). Alpl(-/-)
      mice exhibit many characteristics seen in infantile HPP including long bone and
      tooth defects, vitamin B6 responsive seizures and craniosynostosis. Previous
      reports demonstrated that a mineral-targeted form of TNAP rescues long bone,
      vertebral and tooth mineralization defects in Alpl(-/-) mice. Here we report that
      enzyme replacement with mineral-targeted TNAP (asfotase-alfa) also prevents
      craniosynostosis (the premature fusion of cranial bones) and additional
      craniofacial skeletal abnormalities in Alpl(-/-) mice. Craniosynostosis, cranial
      bone volume and density, and craniofacial shape abnormalities were assessed by
      microscopy, histology, digital caliper measurements and micro CT. We found that
      craniofacial shape defects, cranial bone mineralization and craniosynostosis were
      corrected in Alpl(-/-) mice injected daily subcutaneously starting at birth with
      recombinant enzyme. Analysis of Alpl(-/-) calvarial cells indicates that TNAP
      deficiency leads to aberrant osteoblastic gene expression and diminished
      proliferation. Some but not all of these cellular abnormalities were rescued by
      treatment with inorganic phosphate. These results confirm an essential role for
      TNAP in craniofacial skeletal development and demonstrate the efficacy of early
      postnatal mineral-targeted enzyme replacement for preventing craniofacial
      abnormalities including craniosynostosis in murine infantile HPP. 

PMID- 25959420
TI  - Measuring glomerular filtration rate by iohexol clearance on filter paper is
      feasible in adolescents with type 1 diabetes in the ambulatory setting.

PMID- 25959421
TI  - Effects of long-term resveratrol-induced SIRT1 activation on insulin and
      apoptotic signalling in aged skeletal muscle.
AB  - AIMS: Activation of Foxo1 is known to promote apoptosis and disturbances to
      insulin signalling. However, their modulating roles in aged skeletal muscle are
      not clear. The present study tested the hypothesis that long-term (i.e. 8 month)
      resveratrol supplementation would improve physical traits including exercise
      capacity and basal voluntary activity of aged mice and modulate insulin/apoptotic
      signalling in aged skeletal muscle. This study also examined whether these
      resveratrol-associated alterations would involve orchestration of the SIRT1-Foxo1
      signalling axis. METHODS: Two-month-old SAMP8 mice were randomly assigned to
      young, aged and aged with resveratrol treatment (AR) groups. The AR mice were
      supplemented with 4.9 mg(-1) kg(-1) day(-1) resveratrol for 8 months. All animals
      were subject to endurance capacity test and voluntary motor behaviour assessment.
      The lateral gastrocnemius muscle tissues were harvested for further analyses.
      RESULTS: Long-term resveratrol treatment significantly alleviated the age
      associated reductions in exercise capacity and voluntary motor behaviour. The
      protein content, but not the deacetylase activity of SIRT1 was increased with
      concomitant elevations of p300 acetylase and acetylation of Foxo1 in aged muscle.
      The aged muscle also manifested signs of impaired insulin signalling including
      attenuated phosphorylation of Akt, activity of pyruvate dehydrogenase and
      membrane trafficking of GLUT4 and elevated levels of phosphorylated IRS1 and iNOS
      and apoptotic activation measured as Bim, p53 and apoptotic DNA fragmentation.
      Intriguingly, all these age-related adverse changes were mitigated with the
      activation of SIRT1 deacetylase activity after long-term resveratrol treatment.
      CONCLUSIONS: These data suggest that modulation of the SIRT1-Foxo1 axis by long
      term resveratrol treatment enhances physical traits and alleviates the
      unfavourable changes in insulin and apoptotic signalling in aged muscle.

PMID- 25959422
TI  - Follicle-stimulating hormone associates with prediabetes and diabetes in
      postmenopausal women.
AB  - AIMS: No study explores the association between follicle-stimulating hormone
      (FSH) and glucose metabolism in general women. We aim to investigate whether the
      variation of FSH is associated with prediabetes and diabetes in postmenopausal
      women. METHODS: Our data were from survey on prevalence in East China for
      metabolic diseases and risk factors in 2014. Thousand six hundred and ten
      postmenopausal women at the age of 55-89 who were not using hormone replacement
      therapy were selected. Prediabetes and diabetes were defined according to
      American Diabetes Association 2014 criteria. FSH, luteinizing hormone, total
      testosterone and estradiol were measured by chemiluminescence. Multinomial
      logistic analyses were used for the association of FSH with prediabetes and
      diabetes, and linear regression for the association of FSH with fasting plasma
      glucose (FPG) and HbA1c. RESULTS: Among the participants, 778 (48.3 %) had
      prediabetes and 121 (7.5 %) had newly diagnosed diabetes. In linear regression,
      after full adjustment for demographic variables, metabolic factors, E2 and LH,
      FSH was associated with FPG and HbA1c (P < 0.05). In logistic regression,
      increased quartiles of FSH were associated with significantly decreased odds
      ratios of prediabetes and diabetes (P for trend <0.01). This association was
      attenuated by waist circumference and HOMA-IR, but persisted in fully adjusted
      model (P for trend <0.05) in which, for the lowest compared with the highest
      quartile of FSH, the odds ratios of prediabetes and diabetes were 1.93 (95 % CI
      1.21-3.08; P < 0.01) and 3.02 (95 % CI 1.10-8.31; P < 0.05), respectively.
      CONCLUSIONS: Low FSH was associated with prediabetes and diabetes in
      postmenopausal women. The associations might be partially explained by adiposity
      and insulin resistance.

PMID- 25959423
TI  - A library approach to rapidly discover photoaffinity probes of the mRNA decapping
      scavenger enzyme DcpS.
AB  - Despite its diverse applications, such as identification of the protein binding
      partners of small molecules and investigation of intracellular drug-target
      engagement, photoaffinity labelling (PAL) is intrinsically challenging, primarily
      due to the difficulty in discovering functionally active photoaffinity probes.
      Here we describe the creation of a chemoproteomic library to discover a novel
      photoaffinity probe for DcpS, an mRNA decapping enzyme that is a putative target
      for Spinal Muscular Atrophy. This library approach expedites the discovery of
      photoaffinity probes and expands the chemical biology toolbox to include RNA cap
      binding proteins. 

PMID- 25959424
TI  - The Effectiveness of the Comprehensive Voice Rehabilitation Program Compared With
      the Vocal Function Exercises Method in Behavioral Dysphonia: A Randomized
      Clinical Trial.
AB  - OBJECTIVE: To evaluate the effectiveness of the Comprehensive Voice
      Rehabilitation Program (CVRP) compared with Vocal Function Exercises (VFEs) to
      treat functional dysphonia. STUDY DESIGN: This is a randomized blinded clinical
      trial. METHODS: Eighty voice professionals presented with voice complaints for
      more than 6 months with a functional dysphonia diagnosis. Subjects were
      randomized into two voice treatment groups: CVRP and VFE. The rehabilitation
      program consisted of six voice treatment sessions and three assessment sessions
      performed before, immediately after, and 1 month after treatment. The outcome
      measures were self-assessment protocols (Voice-Related Quality of Life [V-RQOL]
      and Voice Handicap Index [VHI]), perceptual evaluation of vocal quality, and a
      visual examination of the larynx, both blinded. RESULTS: The randomization
      process produced comparable groups in terms of age, gender, signs, and symptoms.
      Both groups had positive outcome measures. The CVRP effect size was 1.09 for the
      V-RQOL, 1.17 for the VHI, 0.79 for vocal perceptual evaluation, and 1.01 for
      larynx visual examination. The VFE effect size was 0.86 for the V-RQOL, 0.62 for
      the VHI, 0.48 for the vocal perceptual evaluation, and 0.51 for larynx visual
      examination. Only 10% of the patients were lost over the study. CONCLUSIONS: Both
      treatment programs were effective. The probability of a patient improving because
      of the CVRP treatment was similar to that of the VFE treatment.

PMID- 25959419
TI  - Incidence and factors associated with the risk of sexually transmitted diseases
      in HIV-infected people seen for care in Italy: data from the Icona Foundation
      cohort.
AB  - OBJECTIVES: The aims of this study were to identify temporal trends in the
      incidence of sexually transmitted diseases (STDs) in a cohort of HIV-infected
      people and to evaluate factors associated with the risk of a new STD diagnosis.
      METHODS: All HIV-infected patients in the Icona Foundation Study cohort enrolled
      after 1998 were included in this study. STD incidence rates (IRs) were calculated
      and stratified by calendar period. Predictors of STDs were identified using a
      Poisson regression model with sandwich estimates for standard errors. RESULTS:
      Data for 9168 participants were analysed [median age 37.3 (range 18-81) years;
      74% male; 30% men who have sex with men (MSM)]. Over 46 736 person-years of
      follow-up (PYFU), 996 episodes of STDs were observed [crude IR 21.3/1000 PYFU;
      95% confidence interval (CI) 20.0-22.6/1000 PYFU]. In multivariable Poisson
      regression analysis, MSM [rate ratio (RR) 3.03; 95% CI 2.52-3.64 versus
      heterosexuals], calendar period (RR 1.67; 95% CI 1.42-1.97 for 2008-2012 versus
      1998-2002), HIV RNA > 50 HIV-1 RNA copies/mL (RR 1.44; 95% CI 1.19-1.74 versus
      HIV RNA <= 50 copies/mL) and a current CD4 count < 100 cells/MUL (RR 4.66; 95% CI
      3.69-5.89; P < 0.001 versus CD4 count > 500 cells/MUL) were associated with an
      increased risk of STDs. In contrast, older age (RR 0.82 per 10 years older; 95%
      CI 0.77-0.89) and being currently on ART (RR 0.38; 95% CI 0.33-0.45) compared
      with being ART-naive or on a treatment interruption were associated with a lower
      risk of developing STDs. CONCLUSIONS: An increase in the incidence of STDs was
      observed in more recent years. Interventions to prevent STDs and potential spread
      of HIV should target the younger population, MSM and people currently not
      receiving ART.

PMID- 25959425
TI  - The Americans With Disabilities Act and Voice Disorders: Practical Guidelines for
      Voice Clinicians.
AB  - OBJECTIVE: The Americans with Disabilities Act Amendments Act of 2008 (ADAAA)
      resulted in changes to the legal definition of disability and substantially
      affected how those with voice disorders may qualify for reasonable accommodations
      under the law. However, there has been little guidance and a lack of awareness
      about these changes within the voice literature. This article examines the
      Americans with Disabilities Act of 1990 (ADA), the changes made in 2008 (ADAAA),
      and how the law applies to individuals with voice disorders. STUDY DESIGN: This
      is a review article. METHODS: The ADA and ADAAA are summarized with a particular
      focus on individuals with voice disorders. Types of reasonable accommodations
      within the workplace are suggested, and online resources are provided which
      outline the disclosure and accommodation process. Practical examples are used to
      provide guidance for clinicians who may be involved in counseling this clinical
      population. RESULTS/CONCLUSIONS: Many individuals with voice disorders may not
      realize that their conditions can be classified as disabilities under the law,
      entitling them to workplace accommodations and time off to pursue medical
      treatment. However, disclosure laws such as the right to refrain from mentioning
      a disability during a job interview may not be protective of individuals with
      severe voice impairments, as symptoms are often difficult to conceal. Clinical
      implications and directions for future research are discussed.

PMID- 25959426
TI  - Beyond the borders--Biomedical applications of non-linear Raman microscopy.
AB  - Raman spectroscopy offers great promise for label free imaging in biomedical
      applications. Its use, however, is hampered by the long integration times
      required and the presence of autofluorescence in many samples which outshines the
      Raman signals. In order to overcome these limitations, a variety of different non
      linear Raman imaging techniques have been developed over the last decade. This
      review describes biomedical applications of these novel but already mature
      imaging techniques. 

PMID- 25959427
TI  - Self-assembling peptide-based delivery of therapeutics for myocardial infarction.
AB  - Cardiovascular disease, including myocardial infarction, is the number one cause
      of death. Current treatments are palliative and slow the progression toward heart
      failure, but to not regenerate healthy tissue. Self-assembling peptides are
      biomimietic, readily produced, non-immunogenic and non-cytotoxic. They do not
      assemble into hydrogels until triggered, allowing them to be injected into the
      myocardium and providing opportunities for minimally invasive therapies. The
      ability to tune the mechanical and bioactive properties of self-assembling
      peptides will continue to make them readily adaptable for mimicking natural
      microenvironments. To date, a variety of growth factors and signaling moieties
      have been incorporated into self-assembling peptide hydrogels, enhancing cell
      behavior and tissue function. Furthermore, the hydrogels serve as delivery
      vehicles for cells in vivo and platforms for improved cell culture. In addition
      to a brief review of self-assembling peptides, we will discuss a variety of their
      approaches for myocardial infarction therapy. Moreover, we will assess approaches
      taken in other tissue and discuss how these could benefit therapies for
      myocardial infarction. 

PMID- 25959428
TI  - Targeted delivery as key for the success of small osteoinductive molecules.
AB  - Molecules such as growth factors, peptides and small molecules can guide cellular
      behavior and are thus important for tissue engineering. They are rapidly emerging
      as promising compounds for the regeneration of tissues of the musculoskeletal
      system. Growth factors have disadvantages such as high cost, short half-life,
      supraphysiological amounts needed, etc. Therefore, small molecules may be an
      alternative. These molecules have been discovered using high throughput
      screening. Small osteoinductive molecules exhibit several advantages over growth
      factors owing to their small sizes, such as high stability and non
      immunogenicity. These molecules may stimulate directly signaling pathways that
      are important for osteogenesis. However, systemic application doesn't induce
      osteogenesis in most cases. Therefore, local administration is needed. This may
      be achieved by using a bone graft material providing additional osteoconductive
      properties. These graft materials can also act by themselves as a delivery matrix
      for targeted and local delivery. Furthermore, vascularization is necessary in the
      process of osteogenesis. Many of the small molecules are also capable of
      promoting vascularization of the tissue to be regenerated. Thus, in this review,
      special attention is given to molecules that are capable of inducing both
      angiogenesis and osteogenesis simultaneously. Finally, more recent preclinical
      and clinical uses in bone regeneration of those molecules are described,
      highlighting the needs for the clinical translation of these promising compounds.

PMID- 25959429
TI  - Toxins and derivatives in molecular pharmaceutics: Drug delivery and targeted
      therapy.
AB  - Protein and peptide toxins offer an invaluable source for the development of
      actively targeted drug delivery systems. They avidly bind to a variety of cognate
      receptors, some of which are expressed or even up-regulated in diseased tissues
      and biological barriers. Protein and peptide toxins or their derivatives can act
      as ligands to facilitate tissue- or organ-specific accumulation of therapeutics.
      Some toxins have evolved from a relatively small number of structural frameworks
      that are particularly suitable for addressing the crucial issues of potency and
      stability, making them an instrumental source of leads and templates for targeted
      therapy. The focus of this review is on protein and peptide toxins for the
      development of targeted drug delivery systems and molecular therapies. We
      summarize disease- and biological barrier-related toxin receptors, as well as
      targeted drug delivery strategies inspired by those receptors. The design of new
      therapeutics based on protein and peptide toxins is also discussed. 

PMID- 25959430
TI  - Homozygous sequence variants in the NPR2 gene underlying Acromesomelic dysplasia
      Maroteaux type (AMDM) in consanguineous families.
AB  - Acromesomelic dysplasia Maroteaux type (AMDM) is an autosomal recessive skeletal
      disorder characterized by disproportionate short stature with shortening of the
      acromesomelic sections of the limbs. AMDM is caused by mutations in the NPR2 gene
      located on chromosome 9p21-p12. The gene encodes the natriuretic peptide receptor
      B (NPR-B) that acts as an endogenous receptor for C-type natriuretic peptide
      (CNP). Both CNP and NPR-B are considered as important regulators of longitudinal
      growth. The study presented here investigated three consanguineous families (A,
      B, C) segregating AMDM in an autosomal recessive manner. Linkage in the families
      was established to the NPR2 gene on chromosome 9p12-21. Sequence analysis of the
      gene revealed two novel missense variants (p.Arg601Ser; p.Arg749Trp) in two
      families and a previously reported splice site variant (c.2986+2T>G) in the third
      family. 

PMID- 25959431
TI  - Facile preparation of a photoactivatable surface on a 96-well plate: a versatile
      and multiplex cell migration assay platform.
AB  - Cell migration is an essential cellular activity in various physiological and
      pathological processes, such as wound healing and cancer metastasis. Therefore,
      in vitro cell migration assays are important not only for fundamental biological
      studies but also for evaluating potential drugs that control cell migration
      activity in medical applications. In this regard, robust control over cell
      migrating microenvironments is critical for reliable and quantitative analysis as
      cell migration is highly dependent upon the microenvironments. Here, we developed
      a facile method for making a commercial glass-bottom 96-well plate
      photoactivatable for cell adhesion, aiming to develop a versatile and multiplex
      cell migration assay platform. Cationic poly-d-lysine was adsorbed to the anionic
      glass surface via electrostatic interactions and, subsequently, functionalized
      with poly(ethylene glycol) (PEG) bearing a photocleavable reactive group. The
      initial PEGylated surface is non-cell-adhesive. However, upon near-ultraviolet
      (UV) irradiation, the photorelease of PEG switches the surface from non
      biofouling to cell-adhesive. With this platform, we assayed cell migration in the
      following procedure: (1) create cell-attaching regions of precise geometries by
      controlled photoirradiation, (2) seed cells to allow them to attach selectively
      to the irradiated regions, (3) expose UV light to the remaining PEGylated regions
      to extend the cell-adhesive area, (4) analyse cell migration using microscopy.
      Surface modification of the glass surface was characterized by zeta-potential and
      contact angle measurements. The PEGylated surface showed cell-resistivity and
      became cell-adhesive upon releasing PEG by near-UV irradiation. The method was
      applied for parallelly evaluating the effect of model drugs on the migration of
      epithelial MDCK cells in the multiplexed platform. The dose-response relationship
      for cytochalasin D treatment on cell migration behavior was successfully
      evaluated with high reproducibility. Interestingly, the impact of blebbistatin on
      cell migration was dependent upon the widths of the migrating regions, resulting
      in both cases of migration acceleration and deceleration. These results clearly
      demonstrate that the cellular response to certain drugs is highly affected by
      their migrating geometries. Therefore, the obtained novel photoactivatable 96
      well plate serves as a useful high-throughput platform for the identification of
      drug candidates that have an effect on cell migration behavior. 

PMID- 25959433
TI  - Does Left Atrial Appendage Morphology Influence Left Atrial Appendage Flow
      Velocity?
AB  - BACKGROUND: The shape of the left atrial appendage (LAA) might affect thrombus
      formation. The chicken wing-type LAA (CW) has been reported as unlikely to
      influence stroke events in atrial fibrillation (AF) patients, so we investigated
      whether LAA shapes could influence LAA function. METHODS AND RESULTS: We studied
      102 patients (64 men, age 65+/-9 years) who underwent transthoracic
      echocardiography, transesophageal echocardiography (TEE), and cardiac computed
      tomography prior to catheter ablation (CA) for AF. LAA morphology were classified
      into 2 types: (1) CW: LAA with a bend in its shape and (2) non-CW type (NCW): LAA
      without any bends. All patients were classified into these groups using a cutoff
      value of LAA flow velocity (LAAFV). Patients with LAAFV <35 cm/s were classified
      as the low LAAFV group (Low FV, n=37). The patients with LAAFV >35 cm/s were
      classified as normal LAAFV group (Normal FV, n=65). The NCW type was detected in
      25/102 patients (25%). In multivariate analysis, the patients with Low FV were
      associated with NCW type (P=0.0429, odds ratio [OR] 9.664, 95% confidence
      interval [CI] 1.075-86.900) and higher B-type natriuretic peptide (BNP)
      (P=0.0350, OR 1.012 for each 1 pg/ml increase in BNP, 95% CI 1.001-1.022).
      CONCLUSIONS: The NCW-type LAA and higher BNP were associated with lower LAAFV.
      One reason for the frequent cardiogenic stroke in patients with the NCW-type LAA
      may be the lower LAAFV.

PMID- 25959432
TI  - Comparison of 3 Risk Estimation Methods for Predicting Cardiac Outcomes in
      Pregnant Women With Congenital Heart Disease.
AB  - BACKGROUND: Three risk estimation methods for predicting the cardiac outcomes of
      pregnancy in women with heart disease have been proposed. This study was designed
      to compare their prediction performance in an Asian cohort with congenital heart
      disease (CHD). METHODS AND RESULTS: This study enrolled pregnant women with CHD
      who delivered their babies after the 20th gestational week between 1985 and 2011.
      Of 268 pregnancies in 190 women with CHD, 18 (6.7%) had cardiac complications.
      The incidence of maternal cardiac events among women with a CARPREG index of 0, 1
      or 2 was 3.4%, 27.3% and 100%. The incidence was 2.7%, 8.6%, 11.1%, 40% and 17.6%
      for those with a ZAHARA score 0-0.5, 0.51-1.5, 1.51-2.5, 2.51-3.5 and >3.5. Among
      patients with a modified World Health Organization (WHO) classification I, II,
      III and IV, the incidence of maternal cardiac events was 0%, 4.0%, 12.2% and
      25.7%. The c-statistic was 0.732 (95% confidence interval (CI): 0.589, 0.876;
      P<0.001) for the CARPREG score, 0.737 (95% CI: 0.611, 0.864; P=0.001) for the
      ZAHARA score and 0.827 (95% CI: 0.745, 0.909; P<0.001) for the WHO
      classification. CONCLUSIONS: All 3 risk estimation methods had good performance
      in predicting maternal cardiac outcomes; however, the modified WHO classification
      demonstrated superior discrimination and calibration.

PMID- 25959434
TI  - Cardiomyopathy With Frequent Ventricular Premature Depolarization - Predicting
      Irreversible Ventricular Dysfunction.
AB  - BACKGROUND: High ventricular premature depolarization (VPD) burden is associated
      with left ventricular (LV) dysfunction that typically resolves after successful
      ablation. Some patients, however, have persistent LV dysfunction, even after
      successful radiofrequency (RF) ablation. Identifying factors associated with
      irreversibility of LV cardiomyopathy (CMP) may help predict clinical outcome.
      METHODS AND RESULTS: Patients with frequent VPD (>10%/day) who underwent
      successful VPD suppression were divided into 2 groups according to transthoracic
      echocardiography (TTE) before and after suppression: group A (n=38) had depressed
      LV function that normalized after VPD suppression; group B (n=19) had depressed
      LV function before and after suppression. Of 57 patients (43 men; mean age, 54+/
      15 years), RF ablation was performed in 39. Clinical, electrocardiographic, and
      TTE parameters were compared between groups. LV end-diastolic dimension (LVEDD;
      group A vs. B: 54+/-5 mm vs. 60+/-10 mm, P=0.01), end-systolic dimension (group A
      vs. B: 42+/-6 mm vs. 48+/-11 mm, P=0.01) before VPD suppression differed
      significantly between groups. Pre-suppression LVEDD was <=66 mm in all reversible
      CMP patients. LVEDD >66 mm predicted irreversible CMP with 50% sensitivity, 100%
      specificity, 100% positive predictive value, and 81% negative predictive value.
      CONCLUSIONS: LVEDD was a good predictor of irreversible LV CMP with frequent VPD,
      with 50% sensitivity and 100% specificity.

PMID- 25959435
TI  - Is an appropriate revascularization selected for unprotected left main coronary
      artery disease?

PMID- 25959436
TI  - A facile synthesis of high quality nanostructured CeO2 and Gd2O3-doped CeO2 solid
      electrolytes for improved electrochemical performance.
AB  - This study describes the use of a composite nitrate salt solution as a precursor
      to synthesize CeO2 and Gd2O3-doped CeO2 (GDC) nanoparticles (NPs) using an
      atmospheric pressure plasma jet (APPJ). The microstructures of CeO2 and GDC NPs
      were found to be cubical and spherical shaped nanocrystallites with average
      particle sizes of 10.5 and 6.7 nm, respectively. Reactive oxygen species,
      detected by optical emission spectroscopy (OES), are believed to be the major
      oxidative agents for the formation of oxide materials in the APPJ process. Based
      on the material characterization and OES observations, the study effectively
      demonstrated the feasibility of preparing well-crystallized GDC NPs by the APPJ
      system as well as the gas-to-particle mechanism. Notably, the Bader charge of
      CeO2 and Ce0.9Gd0.1O2 characterized by density function theory (DFT) simulation
      and AC impedance measurements shows that Gd helps in increasing the charge on
      Ce0.9Gd0.1O2 NPs, thus improving their conductivity and making them candidate
      materials for electrolytes in solid oxide fuel cells. 

PMID- 25959438
TI  - Multi-level logic gate operation based on amplified aptasensor performance.
AB  - Conventional electronic circuits can perform multi-level logic operations;
      however, this capability is rarely realized by biological logic gates. In
      addition, the question of how to close the gap between biomolecular computation
      and silicon-based electrical circuitry is still a key issue in the bioelectronics
      field. Here we explore a novel split aptamer-based multi-level logic gate built
      from INHIBIT and AND gates that performs a net XOR analysis, with electrochemical
      signal as output. Based on the aptamer-target interaction and a novel concept of
      electrochemical rectification, a relayed charge transfer occurs upon target
      binding between aptamer-linked redox probes and solution-phase probes, which
      amplifies the sensor signal and facilitates a straightforward and reliable
      diagnosis. This work reveals a new route for the design of bioelectronic logic
      circuits that can realize multi-level logic operation, which has the potential to
      simplify an otherwise complex diagnosis to a "yes" or "no" decision. 

PMID- 25959437
TI  - A multisite view of psychosocial risks in patients presenting for bariatric
      surgery.
AB  - OBJECTIVE: The psychosocial health of adolescents with severe obesity (BMI >=
      120% for age and gender) has only recently been the focus of empirical work.
      METHODS: This multisite study-an ancillary to a prospective longitudinal
      observational study documenting health in adolescents having weight loss surgery
      (WLS)-presents preoperative/baseline data from 141 WLS adolescents and 83
      nonsurgical comparisons (NSComps). Self-report data from adolescent and caregiver
      dyads characterize adolescent psychopathology and potential correlates. RESULTS:
      One in three adolescents reported internalizing symptoms, and one in five
      endorsed externalizing symptoms in the clinical range. Generalized linear model
      analysis demonstrated that increased risk of psychopathology for adolescents with
      severe obesity was associated with family dysfunction, eating pathology, family
      composition, and seeking behavioral intervention (versus WLS), whereas better
      quality of life (QOL) was associated with lower psychopathology. CONCLUSIONS:
      While psychopathology rates are comparable to national samples, there is a
      subgroup of youth who present for behavioral weight loss services and are at
      greater risk for psychopathology relative to national adolescent base rates.
      Adolescents who achieve candidacy for WLS may be a highly selective population of
      youth with severe obesity and may have lower base rates of psychopathology
      compared to NSComps.

PMID- 25959439
TI  - The centrodistal joint interosseous ligament region in the tarsus of the horse:
      Normal appearance, abnormalities and possible association with other tarsal
      lesions, including osteoarthritis.
AB  - REASONS FOR PERFORMING STUDY: There have been no detailed descriptions of the
      radiological appearance of the centrodistal joint interosseous ligament region in
      horses with and without distal tarsal joint pain. OBJECTIVES: To describe the
      normal radiological appearance of the centrodistal joint interosseous ligament
      region; to determine the prevalence of mineralisation or ossification of the
      interosseous ligament; and to describe radiological abnormalities surrounding the
      interosseous space and concurrent radiological abnormalities in the tarsus. The
      association between interosseous ligament region abnormalities and radiological
      evidence of osteoarthritis of the centrodistal joint was assessed. STUDY DESIGN:
      Retrospective study. METHODS: Case records and radiographs of all horses/ponies
      (n = 700) that underwent radiographic examination of one/both tarsi over 7 years
      were reviewed. Case history, height, bodyweight and cause(s) of lameness were
      recorded. Factors associated with abnormalities of the centrodistal interosseous
      ligament region were assessed using logistic regression analysis. RESULTS: The
      normal interosseous space was an oval or circular-shaped radiolucent area
      bordered proximally and distally by a rim of bone of uniform opacity and
      thickness, which varied in thickness among animals. Abnormalities of the
      interosseous ligament region of the lame(r) limb were evident in 121/700 (17.3%;
      95% confidence interval 14.5-20.1%) animals. Increasing bodyweight was associated
      with decreased odds of interosseous ligament region abnormalities. Forty-seven
      animals (6.7%; 95% confidence interval 4.9-8.6%) had radiological evidence of
      osteoarthritis of the centrodistal joint. A greater proportion of animals with
      interosseous ligament region abnormalities (36.4%) had radiological evidence of
      osteoarthritis of the centrodistal joint, compared to those with normal
      interosseous ligament regions (0.5%; P<0.001). Interosseous ligament region
      abnormalities and osteoarthritis of the centrodistal joint were not necessarily
      associated with distal tarsal joint pain. CONCLUSIONS: There is an association
      between abnormalities of the centrodistal joint interosseous ligament region and
      osteoarthritis. Radiological evidence of abnormalities of the centrodistal
      intertarsal ligament region alone or in association with osteoarthritis may be
      present asymptomatically.

PMID- 25959441
TI  - pH-Tunable wormlike micelles based on an ultra-long-chain "pseudo" gemini
      surfactant.
AB  - Smart surfactant wormlike micelles (SWLMs), responsive to external stimuli, are a
      particularly recent area of development, yet highly promising, given the
      versatility of the materials but simplicity of the design. Here, we developed a
      pH-switchable wormlike micellar system based on a "pseudo" gemini surfactant
      (named as EAMA) formed by a mixture of N-erucamido-N,N-dimethylamine (UC22AMPM)
      and maleic acid with a molar ratio of 2 : 1, and compared the "pseudo" gemini
      worm system with UC22AMPM in the presence of hydrochloric acid (EAHCl). It was
      found that both maleic acid and hydrochloric acid can protonate the ultra-long
      chain tertiary amine into a quaternary ammonium surfactant, thereby forming
      wormlike micelles; however, much stronger viscoelastic behavior was evidenced in
      the maleic acid system because one protonated maleic acid molecule can "bridge"
      two quaternized UC22AMPM molecules via electrostatic attraction. In contrast, the
      EAHCl system just shows a "mono" quaternary ammonium feature with a weak
      viscosity buildup. In addition, the maleic acid-based worm system was found to be
      more thermo-sensitive than conventional wormlike micelles, which also originates
      due to its "pseudo" gemini architecture. 

PMID- 25959440
TI  - Adipose-derived stem cell conditioned medium accelerates keratinocyte
      differentiation via the upregulation of miR-24.

PMID- 25959442
TI  - Potential osteogenic activity of ethanolic extract and oxoflavidin isolated from
      Pholidota articulata Lindley.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Pholidota articulata Lindley (PA) locally known
      as Hadjojen (bone jointer) belongs to family Orchidaceae is used for healing
      fractures in folklore tradition of Kumaon region of Uttarakhand, Himalaya, India.
      Bone is a dynamic organ and is constantly being remodeled in order to facilitate
      growth and repair. This process requires the involvement of bone forming
      osteoblast and bone resorbing osteoclast cells, which function in generating and
      mineralizing bone, giving strength and rigidity to the skeletal system. Present
      study was aimed to determine the therapeutic potential of ethanolic extract of PA
      and its isolated compound oxoflavidin, by characterizing their fracture healing
      properties. MATERIALS AND METHODS: Ovariectomized (Ovx) estrogen deficient adult
      female Balb/c mice were used for in vivo evaluation of osteogenic or bone healing
      potential of ethanolic extract of PA. Further, its isolated compounds were tested
      for their osteogenic efficacy using alkaline phosphatase assay and mineralization
      assay in vitro in mice calvarial osteoblasts. RESULTS: The ethanolic extract of
      PA exhibited significant restoration of trabecular micro-architecture in both
      femoral and tibial bones. Additionally, treatment with PA extract led to better
      bone quality and devoid of any uterine estrogenicity in ovariectomized estrogen
      deficient mice. One of the isolated compound, oxoflavidin enhanced ALP activity
      (a marker of osteoblast differentiation), mineral nodule formation and mRNA
      levels of osteogenic markers like BMP-2, Type 1 Collagen, RUNX-2 and osteocalcin.
      CONCLUSION: These results warrant that ethanolic extract of PA and it's pure
      compound oxoflavidin have fracture healing properties. The extract and
      oxoflavidin exhibit a strong threapeutical potential for the treatment and
      management of postmenopausal osteoporosis.

PMID- 25959444
TI  - Venn Diagrams: JNEB Figures Research.

PMID- 25959443
TI  - Anti-ulcerogenic effect of Zuojin Pill against ethanol-induced acute gastric
      lesion in animal models.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Zuojin Pill (ZJP), a traditional Chinese
      medicinal decoction, contains two herbal drugs: Coptis chinensis Franch. and
      Tetradium ruticarpum (A. Juss.) Hartley in the ratio of 6:1 (w/w). In this study,
      ZJP was evaluated for its gastroprotective potential against mucosal lesions
      induced by ethanol in mice. MATERIALS AND METHODS: 50 mice were assigned to 5
      groups: groups 1 and 2 were given distilled water orally. Group 3 was
      administered omeprazole 20mg/kg, groups 4 and 5 were given ZJP (1g/kg, 2g/kg,
      respectively). After an additional hour, the mice in groups 2-5 received ethanol
      (0.2ml/kg) orally while group 1 received distilled water instead. Mice were
      killed after 4h and their serum and stomachs subjected to further studies. The
      superoxidase dismutase (SOD) activities and malondialdehyde (MDA) level in serum
      were assayed by SOD and MDA kits, respectively. The myeloperoxidase (MPO)
      activities in stomachs were assayed by MPO kit. The levels of inflammatory
      mediators including tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6)
      and interleukin-1beta (IL-1beta) in serum were assayed by enzyme-linked
      immunosorbent assay method (ELISA). Pathological changes were observed by
      hematoxylin-eosin (HE) staining. The levels of nuclear factor-kBp65 (NF-kBp65), P
      NF-kBp65, P-IkBalpha, IkBalpha, P-IKKalpha, IKKalpha, P-IKKbeta, IKKbeta in
      stomachs were assayed by western blot. RESULTS: The data showed that treatment
      with the ZJP markedly attenuated MPO, MDA, TNF-alpha, IL-6, IL-1betaand increased
      SOD; and ZJP also decreased protein levels of P-NF-kBp65, P-IkBalpha, P
      IKKalphaand P-IKKbetain gastric stomachs. CONCLUSION: It was concluded that ZJP
      may represents a potential therapeutic option to reduce the risk of gastric
      ulceration and the gastroprotective activity of ZJP might contribute in adjusting
      the inflammatory cytokine by regulating the NF-kB signaling pathway.

PMID- 25959445
TI  - Process or outcome?

PMID- 25959446
TI  - Effects of Previous Fruit Intake, Descriptive Majority Norms, and Message Framing
      on Fruit Intake Intentions and Behaviors in Dutch Adults Across a 1-Week Period.
AB  - OBJECTIVE: To test the effects of descriptive norm and message framing on fruit
      intake (intentions) in Dutch adults. DESIGN: Randomized pretest-posttest study
      using a 2 * 2 design. SETTING: Internet-based. PARTICIPANTS: Dutch adults
      recruited via leaflets and announcements on intranet and Internet and who
      provided immediate intention (n = 294) and 1-week follow-up intention and fruit
      intake data (n = 177). INTERVENTION: Messages combining information on intake of
      others (low vs high intake) with information about positive or negative outcomes
      of (in)sufficient fruit intake. MAIN OUTCOME MEASURES: Fruit intake intentions
      and fruit intake. ANALYSIS: Analyses of covariance. RESULTS: Those already
      consuming sufficient fruit and receiving negative information about insufficient
      fruit intake increased their motivation to consume sufficient fruit immediately
      (P = .03), but not at 1-week follow-up. Those who read positive information about
      sufficient fruit intake reported higher fruit consumption than those who read
      negative information about insufficient fruit intake (P = .03). This was stronger
      in those already consuming sufficient fruit. There were no effects of descriptive
      norm information (P > .19). CONCLUSIONS AND IMPLICATIONS: Information about
      outcomes was more persuasive than descriptive majority norm information. Effects
      were generally stronger in those already consuming sufficient fruit.

PMID- 25959447
TI  - Vitamin D intake among young Canadian adults: validation of a mobile vitamin D
      calculator app.
AB  - OBJECTIVE: To establish the validity and reproducibility of the dietary component
      of a mobile vitamin D calculator app. METHODS: Participants entered their dietary
      intake into the Vitamin D Calculator app on 3 recording days over 1 month and
      underwent subsequent 24-hour dietary recalls. RESULTS: There were 50 adults (25
      female), aged 18-25 years (mean, 22 +/- 2 years). Paired-samples t tests tested
      for significant differences (P < .05) in mean vitamin D and calcium intake
      between the app and dietary recalls; Bland-Altman plots assessed agreement
      between the 2 measures. Intra-class correlations and Wilcoxon signed-rank tests
      assessed reproducibility of intakes estimated by the app. Mean vitamin D (n = 50)
      and calcium (n = 48) intakes and risk classifications did not differ
      significantly between the 2 measures (P > .05). CONCLUSIONS AND IMPLICATIONS: The
      Vitamin D Calculator app is a valid classification measure for dietary vitamin D
      and calcium intake. This tool could be used by the general public to increase
      awareness and intake of these nutrients.

PMID- 25959448
TI  - Using a Grocery List Is Associated With a Healthier Diet and Lower BMI Among Very
      High-Risk Adults.
AB  - OBJECTIVE: Examine whether use of a grocery list is associated with healthier
      diet and weight among food desert residents. METHODS: Cross-sectional analysis of
      in-person interview data from randomly selected household food shoppers in 2 low
      income, primarily African American urban neighborhoods in Pittsburgh, PA with
      limited access to healthy foods. RESULTS: Multivariate ordinary least-square
      regressions conducted among 1,372 participants and controlling for
      sociodemographic factors and other potential confounding variables indicated that
      although most of the sample (78%) was overweight or obese, consistently using a
      list was associated with lower body mass index (based on measured height and
      weight) (adjusted multivariant coefficient = 0.095) and higher dietary quality
      (based on the Healthy Eating Index-2005) (adjusted multivariant coefficient =
      0.103) (P < .05). CONCLUSIONS AND IMPLICATIONS: Shopping with a list may be a
      useful tool for low-income individuals to improve diet or decrease body mass
      index.

PMID- 25959449
TI  - UNICEF Training Package for Scaling Up Skilled Community Infant and Young Child
      Feeding Counselors: Zimbabwe Experience.

PMID- 25959450
TI  - Arming oncolytic viruses to leverage antitumor immunity.
AB  - INTRODUCTION: Over the past decade, the cytolytic capabilities of oncolytic
      viruses (OVs), exploited to selectively eliminate neoplastic cells, have become
      secondary to their use to elicit a tumor-directed immune response. AREAS COVERED:
      Here, based on an NCBI-PubMed literature survey, we review the efforts undertaken
      to arm OVs in order to improve therapeutic antitumor responses upon
      administration of these agents. Specifically, we explore the different options to
      modulate immune suppression in the tumor microenvironment (TME) and to facilitate
      the generation of effective antitumor responses that have been investigated in
      conjunction with OVs in recent years. EXPERT OPINION: Their induction of
      immunogenic tumor cell death and association with pro-inflammatory signals make
      OVs attractive immunotherapeutic modalities. The first promising clinical results
      with immunologically armed OVs warrant their further optimization and
      development. OVs should be modified to avoid detrimental effects of pre-existent
      anti-OV immunity as well as for increased tumor targeting and selectivity, so as
      to ultimately allow for systemic administration while achieving local immune
      potentiation and tumor elimination in the TME. In particular, a combination of
      trans-genes encoding bispecific T-cell engagers, immune checkpoint blockers and
      antigen-presenting cell enhancers will remove suppressive hurdles in the TME and
      allow for optimal antitumor efficacy of armed OVs.

PMID- 25959451
TI  - [Erratum: Analysis of the Nuchal Transparency (NT) Screening Concept at the
      Gynecologocial Clinic of MHH: A Prospective Follow-Up Study].

PMID- 25959452
TI  - Role of Fitness in the Metabolically Healthy but Obese Phenotype: A Review and
      Update.
AB  - Despite the strong and consistent evidence supporting that a high physical
      fitness (PF) level at any age is a major predictor of a healthier metabolic
      profile, major studies focused on the metabolically healthy but obese (MHO)
      phenotype have ignored the role of PF when examining this phenotype and its
      prognosis. Particularly, the role of its main health-related components such as
      higher cardiorespiratory fitness (CRF) and muscular fitness in the MHO phenotype
      needs to be reviewed in depth. The present review aimed to: 1) contribute to the
      characterization of the MHO phenotype by examining whether MHO individuals are
      fitter than metabolically abnormal obese (MAO) individuals in terms of CRF and
      other PF components; 2) review the role of CRF and other PF components in the
      prognosis of MHO. The studies reviewed suggest that a higher CRF level should be
      considered a characteristic of the MHO phenotype. Likewise, CRF seems to play a
      key role in the prognosis of the MHO individuals, yet this statement is based on
      a single study and future studies need to confirm or contrast these findings.
      Comparability of studies is difficult due to the different definitions used for
      MHO; consequently, the present review makes a proposal for harmonizing this
      definition in adults and in youth. Obesity is still related to an important
      number of comorbidities; therefore, the public health message remains to fight
      against both obesity and low CRF in both adult and pediatric populations. 

PMID- 25959455
TI  - Ambipolar light-emitting organic single-crystal transistors with a grating
      resonator.
AB  - Electrically driven organic lasers are among the best lasing devices due to their
      rich variety of emission colors as well as other advantages, including
      printability, flexibility, and stretchability. However, electrically driven
      lasing in organic materials has not yet been demonstrated because of serious
      luminescent efficiency roll-off under high current density. Recently, we found
      that the organic ambipolar single-crystal transistor is an excellent candidate
      for lasing devices because it exhibits less efficient roll-off, high current
      density, and high luminescent efficiency. Although a single-mode resonator
      combined with light-emitting transistors (LETs) is necessary for electrically
      driven lasing devices, the fragility of organic crystals has strictly limited the
      fabrication of resonators, and LETs with optical cavities have never been
      fabricated until now. To achieve this goal, we improved the soft ultraviolet
      nanoimprint lithography method and demonstrated electroluminescence from a single
      crystal LET with a grating resonator, which is a crucial milestone for future
      organic lasers. 

PMID- 25959456
TI  - Tailoring metal-oxide interfaces of inverse catalysts of TiO2/nanoporous-Au under
      hydrogen oxidation.
AB  - Engineering metal-oxide interfaces in TiO2/nanoporous (np) Au inverse catalysts
      results in enhancement of H2 oxidation activity. While the intrinsic activity of
      the novel np-Au prepared from a Au-Si alloy is low, the activity increased as the
      weight fraction of the TTIP (amount of TiO2) was increased to 0.5 weight%. We
      correlate the change in activity with the active sites at the perimeter interface
      between the TiO2 and np-Au. 

PMID- 25959457
TI  - High efficiency pure blue thermally activated delayed fluorescence molecules
      having 10H-phenoxaborin and acridan units.
AB  - Highly efficient blue thermally activated delayed fluorescence molecules having
      10H-phenoxaborin and acridan units were reported. Pure blue emission peaking at
      around 450 nm with a high external electroluminescence quantum efficiency of
      around 20% was demonstrated. 

PMID- 25959454
TI  - Safety data on 19 vehicles for use in 1 month oral rodent pre-clinical studies:
      administration of hydroxypropyl-beta-cyclodextrin causes renal toxicity.
AB  - Potential new drugs are assessed in pre-clinical in vivo studies to determine
      their safety profiles. The drugs are formulated in vehicles suitable for the
      route of administration and the physicochemical properties of the drug, aiming to
      achieve optimal exposure in the test species. The availability of safety data on
      vehicles is often limited (incomplete data, access restricted/private databases).
      Nineteen potentially useful vehicles that contained new and/or increased
      concentrations of excipients and for which little safety data have been published
      were tested. Vehicles were dosed orally once daily to HanWistar rats for a
      minimum of 28 days and a wide range of toxicological parameters were assessed.
      Only 30% (w/v) hydroxypropyl-beta-cyclodextrin was found unsuitable owing to
      effects on liver enzymes (AST, ALT and GLDH), urinary volume and the kidneys
      (tubular vacuolation and tubular pigment). 20% (v/v) oleic acid caused increased
      salivation and hence this vehicle should be used with caution. As 40% (v/v)
      tetraethylene glycol affected urinary parameters, its use should be carefully
      considered, particularly for compounds suspected to impact the renal system and
      studies longer than 1 month. There were no toxicologically significant findings
      with 10% (v/v) dimethyl sulphoxide, 20% (v/v) propylene glycol, 33% (v/v)
      Miglyol(r)812, 20% (w/v) Kolliphor(r)RH40, 10% (w/v) Poloxamer 407, 5% (w/v)
      polyvinylpyrrolidone K30 or 10% (v/v) Labrafil(r)M1944. All other vehicles tested
      caused isolated or low magnitude effects which would not prevent their use. The
      aim of sharing these data, including adverse findings, is to provide meaningful
      information for vehicle selection, thereby avoiding repetition of animal
      experimentation.

PMID- 25959453
TI  - Decreased levels of autoantibodies against apolipoprotein B-100 antigens are
      associated with cardiovascular disease in systemic lupus erythematosus.
AB  - Increased production of autoantibodies is a characteristic feature of systemic
      lupus erythematosus (SLE) and there is evidence that several of these
      autoantibodies may contribute to increased cardiovascular disease (CVD) in SLE.
      Autoantibodies against the apolipoprotein (apo) B-100 peptides p45 and p210 have
      been associated with a lower CVD risk in non-SLE cohorts. The aim of the present
      study was to investigate how SLE affects the occurrence of these potentially
      protective autoantibodies. The study cohort consisted of 434 SLE patients and 322
      age- and sex-matched population controls. Antibodies against native and
      malondialdehyde (MDA)-modified p45 and p210 were measured by enzyme-linked
      immunosorbent assay (ELISA). SLE patients had significantly lower levels of p210
      immunoglobulin (Ig)G and p45 IgM (both the native and malondialdehyde (MDA)
      modified forms). SLE patients with manifest CVD (myocardial infarction, ischaemic
      cerebrovascular disease or peripheral vascular disease) had lower levels p210 IgG
      and p45 IgM than SLE patients without CVD. Decreased levels of these
      autoantibodies were also observed in SLE patients with permanent organ damage, as
      assessed by the Systemic Lupus International Collaborating Clinics/American
      College of Rheumatology (ACR) Damage Index (SDI). The present findings show that
      patients with SLE, a condition generally characterized by abundance of
      autoantibodies of multiple specificities, have reduced levels of antibodies
      against the apo B-100 antigens p45 and p210 and that the levels of these
      antibodies are reduced further in SLE patients with CVD. These observations
      suggest the possibility that an impaired antibody-mediated removal of damaged LDL
      particles may contribute to the development of vascular complications and organ
      damage in SLE. 

PMID- 25959458
TI  - Preparation and characterization of the RNase H domain of Moloney murine leukemia
      virus reverse transcriptase.
AB  - Moloney murine leukemia virus reverse transcriptase (MMLV RT) contains fingers,
      palm, thumb, and connection subdomains as well as an RNase H domain. The DNA
      polymerase active site resides in the palm subdomain, and the RNase H active site
      is located in the RNase H domain. The RNase H domain contains a positively
      charged alpha-helix called the C helix (H(594)GEIYRRR(601)), that is thought to
      be involved in substrate recognition. In this study, we expressed three versions
      of the RNase H domain in Escherichia coli, the wild-type domain (WT) (residues
      Ile498-Leu671) and two variants that lack the regions containing the C helix
      (Ile593-Leu603 and Gly595-Thr605, which we called DeltaC1 and DeltaC2,
      respectively) with a strep-tag at the N-terminus and a deca-histidine tag at the
      C-terminus. These peptides were purified from the cells by anion-exchange, Ni(2+)
      affinity, and Strep-Tactin affinity column chromatography, and then the tags were
      removed by proteolysis. In an RNase H assay using a 25-bp RNA-DNA heteroduplex,
      WT, DeltaC1, and DeltaC2 produced RNA fragments ranging from 7 to 16 nucleotides
      (nt) whereas the full-length MMLV RT (Thr24-Leu671) produced 14-20-nt RNA
      fragments, suggesting that elimination of the fingers, palm, thumb, and
      connection subdomains affects the binding of the RNase H domain to the RNA-DNA
      heteroduplex. The activity levels of WT, DeltaC1, and DeltaC2 were estimated to
      be 1%, 0.01%, and 0.01% of full-length MMLV RT activity, indicating that the C
      helix is important, but not critical, for the activity of the isolated RNase H
      domain.

PMID- 25959459
TI  - Efficient production of Tymovirus like particles displaying immunodominant
      epitopes of Japanese Encephalitis Virus envelope protein.
AB  - Japanese Encephalitis (JE) is a mosquito borne arboviral infection caused by
      Japanese Encephalitis Virus (JEV). It is a major cause of viral encephalitis in
      Asian countries including India. In the present study, we have used a Tymovirus
      [i.e. Physalis Mottle Virus (PhMV) coat protein (CP)], which forms virus like
      particles (VLPs) as a template to display immunodominant epitopes of JEV envelope
      (E) protein. The immunodominant epitopes of JEV were inserted at the N-terminus
      of the wild type PhMV CP, and these constructs were cloned and expressed in
      Escherichia coli. The chimeric proteins were purified from the inclusion bodies
      and evaluated for VLP formation. The purified protein was identified by Western
      blotting and VLP formation was studied and confirmed by transmission electron
      microscopy and dynamic light scattering. Finally, the immunogenicity was studied
      in mice. Our results indicate that the chimeric protein with JEV epitopes
      assembled efficiently to form VLPs generating neutralizing antibodies. Hence, we
      report the purified chimeric VLP would be a potent vaccine candidate, which needs
      to be evaluated in a mouse challenge model. 

PMID- 25959460
TI  - Corrigendum.

PMID- 25959461
TI  - [GESIDA/National AIDS Plan: Consensus document on antiretroviral therapy in
      adults infected by the human immunodeficiency virus (Updated January 2015)].
AB  - OBJECTIVE: This consensus document is an update of combined antiretroviral
      therapy (cART) guidelines and recommendations for HIV-1 infected adult patients.
      METHODS: To formulate these recommendations, a panel composed of members of the
      AIDS Study Group and the AIDS National Plan (GeSIDA/Plan Nacional sobre el Sida)
      reviewed the efficacy and safety advances in clinical trials, and cohort and
      pharmacokinetic studies published in medical journals (PubMed and Embase) or
      presented in medical scientific meetings. The strength of the recommendations,
      and the evidence that supports them, are based on modified criteria of the
      Infectious Diseases Society of America. RESULTS: In this update, cART is
      recommended for all patients infected by type 1 human immunodeficiency virus (HIV
      1). The strength and level of the recommendation depends on the CD4+T-lymphocyte
      count, the presence of opportunistic diseases or comorbid conditions, age, and
      prevention of transmission of HIV. The objective of cART is to achieve an
      undetectable plasma viral load. Initial cART should always comprise a combination
      of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors, and a third
      drug from a different family. Three out of the ten recommended regimes are
      regarded as preferential (all of them with an integrase inhibitor as the third
      drug), and the other seven (based on a non-nucleoside reverse transcriptase
      inhibitor, a ritonavir-boosted protease inhibitor, or an integrase inhibitor) as
      alternatives. This update presents the causes and criteria for switching cART in
      patients with undetectable plasma viral load, and in cases of virological failure
      where rescue cART should comprise 3 (or at least 2) drugs that are fully active
      against the virus. An update is also provided for the specific criteria for cART
      in special situations (acute infection, HIV-2 infection, and pregnancy) and with
      comorbid conditions (tuberculosis or other opportunistic infections, kidney
      disease, liver disease, and cancer). CONCLUSIONS: These new guidelines update
      previous recommendations related to cART (when to begin and what drugs should be
      used), how to monitor and what to do in case of viral failure or drug adverse
      reactions. cART specific criteria in comorbid patients and special situations are
      equally updated.

PMID- 25959462
TI  - High energetic excitons in carbon nanotubes directly probe charge-carriers.
AB  - Theory predicts peculiar features for excited-state dynamics in one dimension
      (1D) that are difficult to be observed experimentally. Single-walled carbon
      nanotubes (SWNTs) are an excellent approximation to 1D quantum confinement, due
      to their very high aspect ratio and low density of defects. Here we use ultrafast
      optical spectroscopy to probe photogenerated charge-carriers in (6,5)
      semiconducting SWNTs. We identify the transient energy shift of the highly
      polarizable S33 transition as a sensitive fingerprint of charge-carriers in
      SWNTs. By measuring the coherent phonon amplitude profile we obtain a precise
      estimate of the Stark-shift and discuss the binding energy of the S33 excitonic
      transition. From this, we infer that charge-carriers are formed instantaneously
      (<50 fs) even upon pumping the first exciton, S11. The decay of the
      photogenerated charge-carrier population is well described by a model for
      geminate recombination in 1D. 

PMID- 25959463
TI  - Selective endo and exo binding of mono- and ditopic ligands to a rhomboidal
      diporphyrin prism.
AB  - Copper(I) can preferentially form heteroleptic complexes containing two phosphine
      and two nitrogen donors due to steric factors. This preference was employed to
      direct the self-assembly of a porphyrin-faced rhomboidal prism having two
      parallel tetrakis(4-iminopyridyl)porphyrinatozinc(II) faces linked by eight 1,4
      bis(diphenylphosphino)benzene pillars. The coordination preferences of the Cu(I)
      ions and geometries of the ligands come together to generate a slipped-cofacial
      orientation of the porphyrinatozinc(II) faces. This orientation enables selective
      encapsulation of 3,3'-bipyridine (bipy), which bridges the Zn(II) ions of the
      parallel porphyrins, whereas 4,4'-bipy exhibits weaker external coordination to
      the porphyrin faces. Reaction with 2,2'-bipy, by contrast, results in the
      displacement of the tetratopic porphyrin ligand and formation of [{(2,2'
      bipy)Cu(I) }2 (diphosphine)2 ]. The differing strengths of interactions of
      bipyridine isomers with the system allows for a hierarchy to be deciphered,
      whereby 4,4'-bipy may be displaced by 3,3'-bipy, which in turn is displaced by
      2,2'-bipy. 

PMID- 25959464
TI  - Time to break out of the silos.

PMID- 25959465
TI  - New nursing role extends skills and cuts doctor call-outs.

PMID- 25959466
TI  - Solihull reduces decline in checks for looked after children.

PMID- 25959467
TI  - Call to shake off the 'bunker' mentality endemic in health care.

PMID- 25959470
TI  - One Direction backs web cancer initiative for young people.

PMID- 25959469
TI  - Nurse who devised coma tool wins child health award.

PMID- 25959471
TI  - Survey uncovers widespread failures to comply with nutritional standards.

PMID- 25959472
TI  - Parents report confidence and trust in neonatal services.

PMID- 25959473
TI  - MPs urge new government to set up watchdog to monitor patient safety.

PMID- 25959478
TI  - Research essentials.

PMID- 25959480
TI  - Research and commentary. Valuable knowledge about how families manage their
      child's allergy.

PMID- 25959481
TI  - Starting out--Time out to take stock.

PMID- 25959485
TI  - Recovery brings uncertain future.

PMID- 25959486
TI  - Parents' experiences of their child's admission to paediatric intensive care.
AB  - BACKGROUND: Admission of a child to the paediatric intensive care unit (PICU) may
      be one of the most stressful events for parents because the outcome is often
      uncertain. So how do parents cope, and how can we as nurses help them? AIM: To
      explore the lived experiences of parents whose children have been admitted to a
      PICU. METHODS: Using Heidegger's school of interpretative phenomenology, six
      unstructured interviews were conducted. These were transcribed and analysed
      following interpretative phenomenological analysis. Participants were chosen
      through purposive sampling. FINDINGS: Each participant had different emergent
      themes. Themes included trauma, responsibility, anxiety about where the child is,
      post-traumatic stress symptoms and transfer to the ward. CONCLUSION: The lived
      experience of a parent is fraught with varying different emotions, with the
      beginning of the journey and the ending of the PICU admission causing the most
      anxiety.

PMID- 25959487
TI  - Tissue expansion in burn reconstruction: what can the child and family expect?
AB  - A child with a burn injury often has to go through reconstructive surgery after
      it has healed to improve function and cosmetic appearance. Tissue expansion is
      one of the procedures commonly used in the reconstructive process. It requires
      commitment from the child and the family, because it involves several hospital
      visits, including at least two surgical episodes, in addition to a change in
      lifestyle during the process, and there are time and costs involved in
      travelling, including time off work and school. However, most families think that
      the final improvement achieved is worthwhile. Multidisciplinary pre
      reconstruction clinics offer information and individualised support on the
      clinical, practical and psychological aspects of the procedures. The audit
      presented in this article found that attendance at the clinics can improve
      patient education, reduce complications and enhance the experience of the
      children and their families. 

PMID- 25959488
TI  - Developing effective therapeutic relationships with children, young people and
      their families.
AB  - It is imperative that nurses caring for children, young people and their families
      develop and maintain effective, trusting and collaborative therapeutic
      relationships that sit within the scope of professional boundaries. This
      relationship is the nurse's responsibility and should be positive and mutually
      acceptable to all stakeholders. A unique challenge for children's nurses is to
      address and prioritise the child's care needs, while meeting the needs of, and
      empowering, the family. The 6Cs--care, compassion, competence, communication,
      courage, commitment--should underpin care and enable nurses to overcome
      challenges such as time pressures, acute situations or disturbed family
      expectation. Confidentiality and safeguarding should always be observed.

PMID- 25959490
TI  - Compound-Specific delta15N and delta13C Analyses of Amino Acids for Potential
      Discrimination between Organically and Conventionally Grown Wheat.
AB  - We present a study deploying compound-specific nitrogen and carbon isotope
      analysis of amino acids to discriminate between organically and conventionally
      grown plants. We focused on grain samples of common wheat and durum wheat grown
      using synthetic nitrogen fertilizers, animal manures, or green manures from
      nitrogen-fixing legumes. The measurement of amino acid delta(15)N and delta(13)C
      values, after protein hydrolysis and derivatization, was carried out using gas
      chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS). Our
      results demonstrated that delta(13)C of glutamic acid and glutamine in
      particular, but also the combination of delta(15)N and delta(13)C of 10 amino
      acids, can improve the discrimination between conventional and organic wheat
      compared to stable isotope bulk tissue analysis. We concluded that compound
      specific stable isotope analysis of amino acids represents a novel analytical
      tool with the potential to support and improve the certification and control
      procedures in the organic sector. 

PMID- 25959491
TI  - Using Social Media to Share Your Radiology Research: How Effective Is a Blog
      Post?
AB  - PURPOSE: The aim of this study was to compare the volume of individuals who
      viewed online versions of research articles in 2 peer-reviewed radiology journals
      and a radiology blog promoted by social media. METHODS: The authors performed a
      retrospective study comparing online analytic logs of research articles in the
      American Journal of Neuroradiology (AJNR) and the American Journal of
      Roentgenology (AJR) and a blog posting on Radiopaedia.org from April 2013 to
      September 2014. All 3 articles addressed the topic of reporting incidental
      thyroid nodules detected on CT and MRI. The total page views for the research
      articles and the blog article were compared, and trends in page views were
      observed. Factors potentially affecting trends were an AJNR podcast and promotion
      of the blog article on the social media platforms Facebook, Tumblr, and Twitter
      to followers of Radiopaedia.org in February 2014 and August 2014. RESULTS: The
      total numbers of page views during the study period were 2,421 for the AJNR
      article and 3,064 for the AJR article. The Radiopaedia.org blog received 32,675
      page views, which was 13.6 and 10.7 times greater than AJNR and AJR page views,
      respectively, and 6.0 times greater than both journal articles combined. Months
      with activity above average for the blog and the AJNR article coincided with
      promotion by Radiopaedia.org on social media. CONCLUSIONS: Dissemination of
      scientific material on a radiology blog promoted on social media can
      substantially augment the reach of more traditional publication venues. Although
      peer-reviewed publication remains the most widely accepted measure of academic
      productivity, researchers in radiology should not ignore opportunities for
      increasing the impact of research findings via social media.

PMID- 25959489
TI  - Absence of surrogate light chain results in spontaneous autoreactive germinal
      centres expanding V(H)81X-expressing B cells.
AB  - Random recombination of antibody heavy- and light-chain genes results in a
      diverse B-cell receptor (BCR) repertoire including self-reactive BCRs. However,
      tolerance mechanisms that prevent the development of self-reactive B cells remain
      incompletely understood. The absence of the surrogate light chain, which
      assembles with antibody heavy chain forming a pre-BCR, leads to production of
      antinuclear antibodies (ANAs). Here we show that the naive follicular B-cell pool
      is enriched for cells expressing prototypic ANA heavy chains in these mice in a
      non-autoimmune background with a broad antibody repertoire. This results in the
      spontaneous formation of T-cell-dependent germinal centres that are enriched with
      B cells expressing prototypic ANA heavy chains. However, peripheral tolerance
      appears maintained by selection thresholds on cells entering the memory B-cell
      and plasma cell pools, as exemplified by the exclusion of cells expressing the
      intrinsically self-reactive V(H)81X from both pools.

PMID- 25959492
TI  - Thinking outside the box--The associations with cutaneous involvement and
      autoantibody status in systemic sclerosis are not always what we expect.
AB  - OBJECTIVE: To describe the clinical characteristics and survival of anti
      topoisomerase antibody positive (ATA+) limited cutaneous systemic sclerosis
      (lcSSc) and anti-centromere antibody positive (ACA+) diffuse cutaneous systemic
      sclerosis (dcSSc) patients in a large, multicenter SSc cohort. METHODS: Data from
      subjects in the Canadian Scleroderma Research Group (CSRG) cohort were extracted.
      Descriptive statistics were used to summarize the baseline characteristics,
      including sociodemographic, clinical and serological features of lcSSc and dcSSc,
      according to ATA+ and ACA+ subsets. Kaplan-Meier analysis was performed to
      investigate survival by subsets. RESULTS: Of the 551 subjects included in this
      study, 52 (9.4%) had ATA+ lcSSc and 91 (16.5%) had ACA+ dcSSc. Demographic and
      visceral organ involvement (e.g., gastrointestinal symptoms, interstitial lung
      disease, pulmonary hypertension, and scleroderma renal crisis) was associated
      with serologic status more so than with skin subset. On the other hand,
      calcinosis, joint and peripheral vascular manifestations were associated with
      skin rather than antibody status. Survival was associated with both skin and
      autoantibody subsets, with ATA + dcSSc associated with the worse survival
      compared to ATA+ lcSSc (p = 0.0115), ACA+ lcSSc (p = 0.0216) and ACA+ dcSSc (p =
      0.0313). CONCLUSION: This study provides evidence that subsetting using antibody
      markers in addition to extent of skin involvement may predict clinical outcomes
      better than skin or serology alone in SSc. These findings can inform ongoing
      efforts to define more robust SSc subsets compared to those based on the extent
      of skin involvement or serology alone.

PMID- 25959493
TI  - obitools: a unix-inspired software package for DNA metabarcoding.
AB  - DNA metabarcoding offers new perspectives in biodiversity research. This recently
      developed approach to ecosystem study relies heavily on the use of next
      generation sequencing (NGS) and thus calls upon the ability to deal with huge
      sequence data sets. The obitools package satisfies this requirement thanks to a
      set of programs specifically designed for analysing NGS data in a DNA
      metabarcoding context. Their capacity to filter and edit sequences while taking
      into account taxonomic annotation helps to set up tailor-made analysis pipelines
      for a broad range of DNA metabarcoding applications, including biodiversity
      surveys or diet analyses. The obitools package is distributed as an open source
      software available on the following website: http://metabarcoding.org/obitools. A
      Galaxy wrapper is available on the GenOuest core facility toolshed:
      http://toolshed.genouest.org. 

PMID- 25959495
TI  - BK virus screening and management practices among US renal transplant programs: a
      survey.

PMID- 25959494
TI  - TCR ITAM multiplicity is required for the generation of follicular helper T
      cells.
AB  - The T-cell antigen receptor (TCR) complex contains 10 copies of a di-tyrosine
      Immunoreceptor-Tyrosine-based-Activation-Motif (ITAM) that initiates TCR
      signalling by recruiting protein tyrosine kinases. ITAM multiplicity amplifies
      TCR signals, but the importance of this capability for T-cell responses remains
      undefined. Most TCR ITAMs (6 of 10) are contributed by the CD3zeta subunits. We
      generated 'knock-in' mice that express non-signalling CD3zeta chains in lieu of
      wild-type CD3zeta. Here we demonstrate that ITAM multiplicity is important for
      the development of innate-like T-cells and follicular helper T-cells, events that
      are known to require strong/sustained TCR-ligand interactions, but is not
      essential for 'general' T-cell responses including proliferation and cytokine
      production or for the generation of a diverse antigen-reactive TCR repertoire. 

PMID- 25959496
TI  - Risks for mortality and renal replacement therapy in atherosclerotic renovascular
      disease compared with other causes of chronic kidney disease.
AB  - AIM: Patients with atherosclerotic renovascular disease (ARVD) have an increased
      risk for death and likelihood of initiating renal replacement therapy (RRT)
      compared with the general population. No data exist to describe prognosis in ARVD
      compared with other causes of chronic kidney disease (CKD). We compare patient
      outcomes between ARVD and other causes of CKD. METHODS: Patients were selected
      from two prospective observational cohort studies of outcome in ARVD and CKD.
      Multivariate Cox regression was used to compare risk for RRT and death (both
      prior to and following initiation of RRT) between patients with ARVD and other
      causes of CKD. RESULTS: Of 1472 patients (563 (38%) ARVD, 909 (62%) non-ARVD),
      242 (16%) progressed to RRT and 640 (44%) died over a median follow-up period of
      4.1 (2.4-5.6) years. Patients with ARVD had an increased risk for death (HR 1.5
      (1.2-1.8), P < 0.001) but not for RRT (HR 1.0 (0.7-1.4), P = 0.9). The largest
      increase in risk for death was observed relative to renal limited diseases, e.g.
      pyelonephritis (HR 2.4 (1.3-4.5), P = 0.004) and interstitial/infiltrative
      disease (HR 2.2 (1.3-4.5), P = 0.02). Following initiation of RRT, patients with
      ARVD had a significantly increased risk for death compared with patients without
      ARVD (HR 3.3 (2.2-5.0), P < 0.001). CONCLUSIONS: Patients with ARVD as a cause of
      CKD have an increased risk for death both prior to and following initiation of
      RRT. Further work should seek to identify modifiable risk factors relevant to
      prognosis.

PMID- 25959497
TI  - Characterization of a new sn-1,3-regioselective triacylglycerol lipase from
      Malbranchea cinnamomea.
AB  - The thermophilic ascomycetous fungus Malbranchea cinnamomea produces lipases (EC
      3.1.1.3) that allow it to grow efficiently on medium containing triacylglycerol
      substrates such as plant oils or tributyrin as sole carbon source. In the
      transcriptome of M. cinnamomea grown on olive oil, we found one cDNA sequence
      encoding a putative extracellular lipase. This gene, termed as MclipA, was cloned
      and heterologously expressed in Pichia pastoris. The recombinant protein,
      rMclipA, catalyzed the hydrolysis of short-chain fatty acid ester such as p
      nitrophenyl butyrate (C4) and long-chain fatty acid ester such as p-nitrophenyl
      myristate (C14). These results indicate that MclipA is a true triacylglycerol
      lipase. For rMclipA, the optimum lipase activity was obtained at 45  degrees C,
      and more than 93% of enzyme activity was retained after 24 H of incubation at
      temperatures up to 50  degrees C. rMclipA was active toward p-nitrophenyl esters
      of various carbon chain lengths with peak activity on long-chain fatty acid
      (C14). rMclipA displayed high sn-1,3-regioselectivity on hydrolyzing triolein.
      rMclipA can catalyze oleic acid methyl ester synthesis resulting in a 71%
      esterification degree after 24 H of reaction at 40  degrees C. These properties
      suggest that rMclipA has potential application in, for example, selective
      hydrolysis of oil, modification of triacylglycerol, and production of biodiesel. 

PMID- 25959499
TI  - Intravenous Thrombolysis with Recombinant Tissue-type Plasminogen Activator for
      Acute Ischemic Stroke in Patients with Metabolic Syndrome.
AB  - BACKGROUND: The metabolic syndrome (MetS) is common in patients with acute
      ischemic stroke (IS); however, its impact on outcome after intravenous
      thrombolysis (iv-thrombolysis) remains unclear. Thus, we aimed at evaluating the
      relationship between MetS and functional long-term outcome, mortality, and the
      presence of hemorrhagic complications in patients with IS treated with iv
      thrombolysis. METHODS: We retrospectively evaluated the demographic and clinical
      data of 535 Caucasian patients with acute IS who were consecutively treated with
      iv-thrombolysis from September 2006 to June 2013 in 2 experienced stroke centers
      in Poland. A favorable functional long-term outcome was defined as a modified
      Rankin scale score less than or equal to 2 points on day 90, and hemorrhagic
      complications were assessed with European Cooperative Acute Stroke Study
      criteria. RESULTS: MetS was recognized in 192 (35.9%) patients (44.8% men; mean
      age, 70.8 +/- 11.1 years), diabetes in 29.7%, dyslipidemia in 79.2%, and arterial
      hypertension in 75.5%. At 3 months, favorable outcome was found in 55.3% of
      patients, symptomatic intracerebral hemorrhage (SICH) in 18.3%, and 4.4 % of
      patients died. There was no difference regarding the presence of favorable
      outcome between patients with and without MetS (52.6% versus 56.9%, P = .34). The
      presence of SICH and 3-month mortality were more frequent in patients with MetS
      than without MetS (6.8% versus 2.9%, P = .03 and 23.4% versus 15.5%, P = .02,
      respectively); however, a multivariate analysis showed no impact of MetS on
      mortality or SICH. CONCLUSIONS: Results of our study provide no data to suggest
      that the effect of intravenous tissue-type plasminogen activator differs based on
      the presence or absence of MetS.

PMID- 25959498
TI  - lncRNA GAS5 enhances G1 cell cycle arrest via binding to YBX1 to regulate p21
      expression in stomach cancer.
AB  - Long non-coding RNAs (lncRNAs), which have evolved as important gene expression
      modulators, are involved in human malignancies. The down-regulation of lncRNA
      growth arrest specific transcript 5 (GAS5) has been reported in several cancers,
      however, the underlying mechanism of lncRNA GAS5 in stomach cancer is poorly
      understood. In this study, we found that lncRNA GAS5 had lower expression in
      stomach cancer tissues than the normal counterparts. lncRNA GAS5 was shown to
      interact with Y-box binding protein 1 (YBX1), and lncRNA GAS5 knockdown was shown
      to accelerate YBX1 protein turnover without affecting YBX1 transcription. lncRNA
      GAS5 down-regulation reduced the YBX1 protein level, which decreased YBX1
      transactivated p21 expression and abolished G1 phase cell cycle arrest in stomach
      cancer. These results delineate a novel mechanism of lncRNA GAS5 in suppressing
      stomach carcinogenesis, and the lncRNA GAS5/YBX1/p21 pathway we discovered may
      provide useful targets for developing lncRNA-based therapies for stomach cancer. 

PMID- 25959500
TI  - Systemic Inflammatory Response Syndrome Predicts Severity of Stroke and Outcome.
AB  - BACKGROUND: This study was undertaken to evaluate the frequency of systemic
      inflammatory response syndrome (SIRS) at admission and its correlation with
      clinical and radiological severity of stroke and outcome. METHODS: Two hundred
      consecutive stroke patients within 48 hours of ictus were prospectively included,
      and their clinical details including Glasgow Coma Scale (GCS), National
      Institutes of Health Stroke Scale (NIHSS), and feature of raised intracranial
      tension were noted. Computed tomography/magnetic resonance imaging finding
      included stroke type, location, size, midline shift, herniation, and
      intraventricular hemorrhage score. SIRS was noted on days 1, 2, 7, and 15. Death
      and outcome at 3 months were based on modified Rankin Scale (mRS) score. RESULTS:
      Seventy-five (37.5%) had infraction and 125(62.5%) intracranial hemorrhage (ICH).
      SIRS was present in 120 (60%) patients: all the features in 56 (28%), 3 in 48
      (24%), and 2 in 16 (8%). The presence of SIRS decreased with time: on the second
      day in 57%, seventh day in 43%, and 15th day in 21% of patients. Admission SIRS
      correlated with the GCS score (P < .001), NIHSS score (P < .001), volume of ICH
      (P < .001), infarction size (P < .001), hypernatremia (P = .001), and respiratory
      paralysis (P < .001). Thirty-one (15.5%) patients died, and 30 (97%) of them had
      SIRS. At 3 months, 110 (55%) patients had poor outcome (mRS >2) and of them 90
      (82%) had SIRS (P < .001). On multivariate regression analysis, the number of
      SIRS criteria (P = .16) was not significantly related to 3-month outcome and
      death but independently related to NIHSS score at admission (odds ratio [OR] =
      1.39; 95% confidence interval [CI] = 1.22-1.56; P < .001), GCS score (OR = 1.32;
      95% CI = 1.01-1.71; P = .04), and duration of hospitalization (OR = 1.07; 95% CI
      = 1.01-1.15; P = .03). CONCLUSIONS: SIRS at presentation is a useful marker for
      clinicoradiological severity of stroke but not an independent marker of death and
      disability.

PMID- 25959501
TI  - Higher Left Ventricle Mass Indices Predict Favorable Outcome in Stroke Patients
      with Thrombolysis.
AB  - BACKGROUND: We sought to assess the association of left ventricle mass (LVM)
      indices with the functional outcome of acute ischemic stroke (AIS) patients after
      intravenous tissue plasminogen activator (IV-tPA). METHODS: Consecutive AIS
      patients with IV-tPA were recruited. LVM indices including LVM/weight,
      LVM/surface, and LVM/height^(2.7) on echocardiogram during hospitalization were
      retrospectively reviewed. Outcome was 90-day modified Rankin scale (mRS) scores.
      Multivariate logistic regression was performed to analyze the association of LVM
      indices with outcome. RESULTS: Between August 2010 and May 2014, 55 AIS patients
      (age range from 27 to 78 years, 69.1% men) with echocardiogram after thrombolysis
      were recruited. Lower baseline National Institutes of Health Stroke Scale (NIHSS;
      P = .009) and higher LVM indices (LVM/weight [P = .012], LVM/surface [P = .039],
      and LVM/height^(2.7) [P = .045]) were significantly associated with 90-day
      favorable outcome (mRS, 0-2). In multivariate logistic regression analysis,
      LVM/weight independently predicted good outcome with an odds ratio of 3.89 (95%
      confidence interval, 1.05-14.42, P = .042) after adjustment for baseline NIHSS,
      onset-to-treatment time, hypertension, hemorrhagic transformation, and systolic
      left ventricle inner diameters. CONCLUSIONS: Higher LVM indices on echocardiogram
      are significantly associated with favorable outcome in stroke patients with IV
      tPA, among which LVM/weight seems to be the most effective.

PMID- 25959502
TI  - Motivational interviewing and interaction skills training for parents of young
      adults with recent-onset schizophrenia and co-occurring cannabis use: 15-month
      follow-up.
AB  - BACKGROUND: There is a clear need for effective interventions to reduce cannabis
      use in patients with first-episode psychosis. This follow-up of a randomized
      trial examined whether an intervention for parents, based on motivational
      interviewing and interaction skills (Family Motivational Intervention, FMI), was
      more effective than routine family support (RFS) in reducing cannabis use in
      patients with recent-onset schizophrenia. METHOD: In a single-blind trial with 75
      patients in treatment for recent-onset schizophrenia, 97 parents were randomly
      assigned to either FMI or RFS. Assessments were conducted at baseline and at 3
      and 15 months after the interventions had been ended. Analyses were performed on
      an intention-to-treat basis using mixed-effect regression models. RESULTS: From
      baseline to the 15-month follow-up, there was a significantly greater reduction
      in FMI compared to RFS in patients' quantity (p = 0.01) and frequency (p < 0.01)
      of cannabis use. Patients' craving for cannabis use was also significantly lower
      in FMI at 15 months follow-up (p < 0.01). Both groups improved in parental
      distress and sense of burden; however, only FMI parents' appraisal of patients'
      symptoms showed further improvement at the 15-month follow-up (p < 0.05).
      CONCLUSIONS: The results support the sustained effectiveness of FMI in reducing
      cannabis use in patients with recent-onset schizophrenia at 15 months follow-up.
      Findings were not consistent with regard to the long-term superiority of FMI over
      RFS in reducing parents' distress and sense of burden.

PMID- 25959503
TI  - Hippocampal (subfield) volume and shape in relation to cognitive performance
      across the adult lifespan.
AB  - Newer approaches to characterizing hippocampal morphology can provide novel
      insights regarding cognitive function across the lifespan. We comprehensively
      assessed the relationships among age, hippocampal morphology, and hippocampal
      dependent cognitive function in 137 healthy individuals across the adult lifespan
      (18-86 years of age). They underwent MRI, cognitive assessments and genotyping
      for Apolipoprotein E status. We measured hippocampal subfield volumes using a new
      multiatlas segmentation tool (MAGeT-Brain) and assessed vertex-wise (inward and
      outward displacements) and global surface-based descriptions of hippocampus
      morphology. We examined the effects of age on hippocampal morphology, as well as
      the relationship among age, hippocampal morphology, and episodic and working
      memory performance. Age and volume were modestly correlated across hippocampal
      subfields. Significant patterns of inward and outward displacement in hippocampal
      head and tail were associated with age. The first principal shape component of
      the left hippocampus, characterized by a lengthening of the antero-posterior axis
      was prominently associated with working memory performance across the adult
      lifespan. In contrast, no significant relationships were found among subfield
      volumes and cognitive performance. Our findings demonstrate that hippocampal
      shape plays a unique and important role in hippocampal-dependent cognitive aging
      across the adult lifespan, meriting consideration as a biomarker in strategies
      targeting the delay of cognitive aging.

PMID- 25959504
TI  - Validation of daily increments and a marine-entry check in the otoliths of
      sockeye salmon Oncorhynchus nerka post-smolts.
AB  - Juvenile sockeye salmon Oncorhynchus nerka that were reared and smolted in
      laboratory conditions were found to produce otolith daily increments, as well as
      a consistently visible marine-entry check formed during their transition to salt
      water. Field-collected O. nerka post-smolts of an equivalent age also displayed
      visible checks; however, microchemistry estimates of marine-entry date using
      Sr:Ca ratios differed from visual estimates by c. 9 days suggesting that
      microstructural and microchemical processes occur on different time scales. 

PMID- 25959505
TI  - What Exactly is Midwifery Practice?

PMID- 25959506
TI  - Refining the chemical toolbox to be fit for educational and practical purpose for
      drug discovery in the 21st Century.
AB  - We live in a time where exploration and generation of new knowledge is occurring
      on a colossal scale. Medicinal chemists have traditionally taken key roles in
      drug discovery; however, the many unmet medical demands in the healthcare sector
      emphasise the need to evolve the medicinal chemistry discipline. To rise to the
      challenges in the 21st Century there is a necessity to refine the chemical
      toolbox for educational and practical reasons. This review proposes modern
      strategies that are beneficial to teaching in academia but are also important
      reminders of strategies that can potentially lead to better drugs. 

PMID- 25959507
TI  - Isolation and characterisation of insulin-releasing compounds from Crotalus
      adamanteus, Crotalus vegrandis and Bitis nasicornis venom.
AB  - Crude venom from three venomous snakes, Crotalus adamanteus, Crotalus vegrandis
      and Bitis nasicornis was fractionated by gel filtration chromatography, and
      selected fractions screened for in-vitro insulinotropic activity using clonal
      pancreatic BRIN-BD11 cells. Nineteen fractions stimulated insulin secretion and
      the structural identity of bioactive compounds responsible was probed using MALDI
      ToF MS and N-terminal Edman degradation sequencing. Partial N-terminal sequences
      were determined and their homology to existing sequences identified using BLAST
      searching. The main insulinotropic peptide families identified were made up of
      snake venom serine proteinases, phospholipases A2 (PLA2) and disintegrins. Snake
      venom constituents may have therapeutic potential for diabetes, with each of the
      three viper venoms tested providing insulinotropic compounds from a range of
      different toxin families. 

PMID- 25959508
TI  - Prothrombin activator-like toxin appears to mediate cardiovascular collapse
      following envenoming by Pseudonaja textilis.
AB  - Brown snake (Pseudonaja spp.)-induced early cardiovascular collapse is a life
      threatening medical emergency in Australia. We have previously shown that this
      effect can be mimicked in animals and is mediated via the release of endogenous
      mediators. In the present study, we aimed to purify and characterize the
      component in Pseudonaja textilis venom which induces cardiovascular collapse
      following envenoming. The component (fraction 3) was isolated using a combination
      of techniques including hydroxyapatite and reverse phase chromatography. Fraction
      3 (10 or 20 MUg/kg, i.v.) produced a rapid decrease in mean arterial pressure
      (MAP) followed by cardiovascular collapse. Fraction 3-induced early collapse was
      abolished by prior administration of smaller priming doses of fraction 3 (i.e. 2
      and 5 MUg/kg, i.v.) or heparin (300 units/kg, i.v.). P. textilis whole venom (1
      and 3 MUg/ml), but not fraction 3 (1 or 3 MUg/ml), induced endothelium-dependent
      relaxation in isolated rat mesenteric arteries. SDS-PAGE gel indicated the
      presence of 9-10 protein bands of fraction 3. Using proteomic based analysis some
      protein bands of fraction 3 were identified as subunits of venom prothrombin
      activator, pseutarin C of P. textilis venom. Our results conclude that
      prothrombin activator-like toxin is likely to be a contributor to the rapid
      collapse induced by P. textilis venom. 

PMID- 25959509
TI  - PKA and CDK5 can phosphorylate specific serines on the intracellular domain of
      podoplanin (PDPN) to inhibit cell motility.
AB  - Podoplanin (PDPN) is a transmembrane glycoprotein that promotes tumor cell
      migration, invasion, and cancer metastasis. In fact, PDPN expression is induced
      in many types of cancer. Thus, PDPN has emerged as a functionally relevant cancer
      biomarker and chemotherapeutic target. PDPN contains 2 intracellular serine
      residues that are conserved between species ranging from mouse to humans. Recent
      studies indicate that protein kinase A (PKA) can phosphorylate PDPN in order to
      inhibit cell migration. However, the number and identification of specific
      residues phosphorylated by PKA have not been defined. In addition, roles of other
      kinases that may phosphorylate PDPN to control cell migration have not been
      investigated. We report here that cyclin dependent kinase 5 (CDK5) can
      phosphorylate PDPN in addition to PKA. Moreover, results from this study indicate
      that PKA and CDK5 cooperate to phosphorylate PDPN on both intracellular serine
      residues to decrease cell motility. These results provide new insight into PDPN
      phosphorylation dynamics and the role of PDPN in cell motility. Understanding
      novel mechanisms of PDPN intracellular signaling could assist with designing
      novel targeted chemotherapeutic agents and procedures. 

PMID- 25959511
TI  - The suspensory apparatus of the distal phalanx in normal horses.
AB  - REASONS FOR PERFORMING STUDY: The suspensory apparatus of the distal phalanx
      (SADP) is functionally and clinically important. OBJECTIVES: To investigate SADP
      form and function and the microanatomy of its insertion zone. STUDY DESIGN:
      Descriptive gross and microanatomy. METHODS: The feet of 6 normal Standardbred
      horses were sectioned into blocks along the traditional perpendicular transverse
      axis and along functional axes of the SADP, decalcified and processed for
      staining with haematoxylin and eosin, Jones' periodic acid silver methenamine or
      Masson's trichrome stains. RESULTS: In traditional midline toe transverse plane
      sections SADP collagen bundles were irregular with an unstructured appearance. In
      sections made transversely along planes (70 degrees  and 30 degrees ) aligned
      with the long axis of the SADP, collagen bundles were arranged in linear rows.
      The linear bundles were continuous from their origin on parietal ridges of the
      distal phalanx through to the secondary epidermal lamellar basement membrane. At
      the parietal ridge interface the collagen bundles coalesced into smaller,
      strongly silver staining, linear structures that penetrated the cortical bone and
      merged with adjacent osteons. In proximal sagittal sections collagen bundles were
      also linear, angled at 70 degrees  to the ground surface. In distal sagittal
      sections collagen bundles were also arranged linearly but in a multi-angled,
      'spokes of a wheel' arrangement, centred on the distal phalanx apex. CONCLUSIONS:
      Sectioning along functional axes demonstrated the true suspensory nature of the
      SADP connecting the parietal surface to the lamellar hoof wall. SADP/distal
      phalanx insertions showed penetrating fibres extending through the chondral
      apophyseal interface up to and between distal phalanx osteons. Lamellar
      measurements made from sections perpendicular to the dorsal aspect of the distal
      phalanx are underestimations but if made along the longer, functional midline 70
      degrees  transverse plane would accurately reflect the suspensory function of the
      lamellae. Laminitis pathophysiology correctly viewed as SADP degradation should
      inform logical, future therapeutic strategies.

PMID- 25959510
TI  - The sensitivity of nonlinear computational models of trabecular bone to tissue
      level constitutive model.
AB  - Microarchitectural finite element models have become a key tool in the analysis
      of trabecular bone. Robust, accurate, and validated constitutive models would
      enhance confidence in predictive applications of these models and in their
      usefulness as accurate assays of tissue properties. Human trabecular bone
      specimens from the femoral neck (n = 3), greater trochanter (n = 6), and lumbar
      vertebra (n = 1) of eight different donors were scanned by MU-CT and converted to
      voxel-based finite element models. Unconfined uniaxial compression and shear
      loading were simulated for each of three different constitutive models: a
      principal strain-based model, Drucker-Lode, and Drucker-Prager. The latter was
      applied with both infinitesimal and finite kinematics. Apparent yield strains
      exhibited minimal dependence on the constitutive model, differing by at most
      16.1%, with the kinematic formulation being influential in compression loading.
      At the tissue level, the quantities and locations of yielded tissue were
      insensitive to the constitutive model, with the exception of the Drucker-Lode
      model, suggesting that correlation of microdamage with computational models does
      not improve the ability to discriminate between constitutive laws. Taken
      together, it is unlikely that a tissue constitutive model can be fully validated
      from apparent-level experiments alone, as the calculations are too insensitive to
      identify differences in the outcomes. Rather, any asymmetric criterion with a
      valid yield surface will likely be suitable for most trabecular bone models. 

PMID- 25959512
TI  - Pediatric linear scleroderma initially developed with angioma serpiginosum-like
      appearances.

PMID- 25959513
TI  - Mechanisms of chromosome segregation in meiosis--new views on the old problem of
      aneuploidy.

PMID- 25959514
TI  - Speciation of inorganic arsenic species and total inorganic arsenic in rice using
      microwave-assisted dispersive liquid-liquid micro-extraction and electrothermal
      atomic absorption spectrometry.
AB  - Human exposure to inorganic arsenic (iAs) via rice consumption is of increasing
      concern. In the present study, microwave-assisted dispersive liquid-liquid micro
      extraction (MADLLME) and electrothermal atomic absorption spectrometry (ETAAS)
      were developed for the speciation of iAs in rice samples. After microwave
      assisted digestion, the As(III) ion reacted with diethyldithiophosphoric acid
      (DDTP) to form an As-DDTP complex and was extracted at the same time. Some
      parameters affecting digestion, complex formation, and extraction were studied
      and optimised. Under the optimised conditions, a detection limit of 0.2 ug kg(-1)
      with a correlation coefficient of 0.9901 were obtained with a calibration curve
      in the range of 0.5-200 ug kg(-1). Total iAs was determined after reduction of
      As(V) to As(III) with sodium thiosulfate and potassium iodide, and As(V) was
      calculated by difference. The proposed extraction procedure was successfully
      applied for the determination of iAs ions in certified reference materials (NIST
      CRM 1568a and NMIJ CRM 7503a) and 10 rice samples produced in Iran and other
      Asian countries.

PMID- 25959515
TI  - Early-onset, severe, and recurrent primary hyperparathyroidism associated with a
      novel CDC73 mutation.
AB  - Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare autosomal dominant
      hereditary tumor syndrome characterized by synchronous or metachronous occurrence
      of primary hyperparathyroidism (PHPT), ossifying fibroma of the maxilla and/or
      mandible, renal tumor and uterine tumors. Early diagnosis of this syndrome is
      essential because it is associated with increased risk of parathyroid cancer. A
      30-year-old man with urolithiasis had severe hypercalcemia (15.0 mg/dL after
      correction) induced by inappropriate parathyroid hormone (PTH) secretion (intact
      PTH 1390 pg/mL), indicating severe PHPT. An underlying parathyroid tumor was
      surgically removed and was histologically confirmed to be an adenoma. However,
      PHPT due to another parathyroid tumor reoccurred two years after the surgery.
      Although no HPT-JT-associated manifestations other than PHPT were detected, HPT
      JT was strongly suspected based on the exclusion of multiple endocrine neoplasia
      (MEN) and the young age of disease occurrence. Genetic analysis revealed a novel
      nonsense mutation (p.Arg91X; c.271C>T) in exon 3 of the causative gene, CDC73,
      which encodes the tumor suppressor protein parafibromin. The residual parathyroid
      glands were all removed without autotransplantation of parathyroid gland taking
      into consideration prospective parathyroid carcinogenesis. The resected
      parathyroid tumor was also an adenoma. The present case highlights that HPT-JT
      should be considered and CDC73 mutation analysis should be performed, especially
      in cases of early-onset PHPT, recurrent PHPT, PHPT with polyglandular parathyroid
      involvement, and PHPT presenting with severe hypercalcemia even if there is no
      positive family history. 

PMID- 25959517
TI  - Sequence analysis of EBV immune evasion gene BNLF2a in EBV associated tumors and
      healthy individuals from nasopharyngeal carcinoma endemic and non-endemic regions
      of China.
AB  - BNLF2a is an Epstein-Barr virus (EBV) immune evasion gene. Its protein is located
      in the endoplasmic reticulum (ER) membrane, and can inhibit the antigen
      transporting function of TAP, thereby perturbing the immune response to EBV in
      lytic and prelatent phase. In order to explore whether the polymorphism of BNLF2a
      gene has a role in different types of EBV associated tumors, we conducted
      complete sequencing of the gene BNLF2a in 408 cases of EBV positive tumors (76
      lymphomas, 45 gastric carcinomas, and 85 nasopharyngeal carcinomas in northern
      China and 27 lymphomas, 30 gastric carcinomas, and 57 nasopharyngeal carcinomas
      in southern China) and throat washings from healthy individuals (39 in northern
      China and 49 in southern China). Two main variant types of BNLF2a were
      identified. Type BNLF2a-A, which was similar to B95-8, was dominant in all sub
      populations (66.7-100%) in this study. Type BNLF2a-B was characterized by the
      mutations at position 8 and 40. The variation patterns of BNLF2a were
      significantly different between samples from northern and southern China (P <
      0.05), and between the tumors and healthy donor samples from the northern China
      (P < 0.0167). Type BNLF2a-B was more frequent in healthy donors of northern China
      (33.3%), and the proportion of this type was higher in the northern than in the
      southern NPCs. These data demonstrate that the BNLF2a gene is highly conserved,
      and its polymorphism is geographically restricted. Type BNLF2a-B is more
      prevalent in northern China and may be less tumor transformative.

PMID- 25959516
TI  - Predictors for selection of insurance-funded weight loss approaches in
      individuals with severe obesity.
AB  - OBJECTIVE: To determine whether there are differences in baseline psychological
      and behavioral characteristics between individuals with severe obesity who chose
      a surgical or nonsurgical intervention for weight loss. METHODS: The current
      study utilized data from a larger study funded by a state insurance company and
      is unique in that the insurance company funded the weight loss interventions.
      Participants indicated their preferred method of weight loss, and completed
      several self-report psychological questionnaires, as well as demographic
      information. RESULTS: Participants (N = 605) were 58.8% Caucasian and mostly
      (86%) female. Logistic regression results indicated that an increased number of
      weight loss attempts, and select other measures of eating behavior and quality of
      life may influence individuals' selection for either surgical or nonsurgical
      treatments for weight loss. CONCLUSIONS: Practitioners should pay particular
      attention to these baseline characteristics that influence choice to examine
      potential characteristics that may influence the success of these weight loss
      treatments.

PMID- 25959518
TI  - [The psychological counseling in the long-term follow-up in oncology: Review and
      prospects].
AB  - The aim of the article is to describe psychological counseling implemented in the
      context of the study of the long-term follow-up in oncology (SALTO in Rhone-Alpes
      Auvergne and in Gustave-Roussy). The authors address the specificity of this
      consultation, proposed to adults who had childhood cancer, focusing in particular
      on the observed psychic movements. To conclude, the authors justify the interest
      of a clinical approach and the necessity of such psychological consultation for
      these former patients became adults. 

PMID- 25959519
TI  - [The low doses of radiation: Towards a new reading of the risk assessment].
AB  - From Hiroshima bomb explosion data, the risk of radiation-induced cancer is
      significant from 100 mSv for a population considered as uniform and
      radioresistant. However, the recent radiobiological data bring some new elements
      that highlight some features that were not taken into account: the individual
      factor, the dose rate and the repeated dose effect. The objective evaluation of
      the cancer risk due to doses lower than 100 mSv is conditioned by high levels of
      measurability and statistical significance. However, it appears that
      methodological rigor is not systematically applied in all the papers.
      Furthermore, unclear communication in press often leads to some announcement
      effects, which does not improve the readability of the issue. This papers aims to
      better understand the complexity of the low-dose-specific phenomena as a whole,
      by confronting the recent biological data with epidemiological data. 

PMID- 25959520
TI  - Psychometric performance of the English language six-item Caring Behaviours
      Inventory in an acute care context.
AB  - AIMS AND OBJECTIVES: This study aimed to evaluate the psychometric performance of
      the six-item Caring Behaviours Inventory in a sample of Australian acute hospital
      inpatients. BACKGROUND: Caring is significant for nursing, and exploring the
      prevalence of staff-caring behaviours is imperative for high-quality acute care.
      There is a need for psychometrically sound scales that measures caring in acute
      care, without imposing extensive respondent burden. DESIGN: A cross-sectional
      survey design was used to distribute the six-item Caring Behaviours Inventory to
      an Australian sample of hospital inpatients (n = 210) in December 2012. METHOD:
      Psychometric evaluation included item performance, construct validity and
      internal consistency reliability. RESULTS: The six-item Caring Behaviours
      Inventory had satisfactory psychometric performance as evidenced by normally
      distributed scores, a uni-dimensional structure explaining 65% of variance in
      data, a total Cronbach's alpha of 0.89 and corrected item-total correlations
      between 0.51-0.82. CONCLUSION: The six-item Caring Behaviours Inventory had
      satisfactory estimates of validity and reliability when tested in an Australian
      sample of acute hospital inpatients. The tool contributes to the literature by
      being a brief and nonburdensome alternative with seemingly strong psychometric
      properties to be used in future measures of caring in nursing. RELEVANCE TO
      CLINICAL PRACTICE: The six-item Caring Behaviours Inventory provides a
      psychometrically tested fundament for reflective clinical discussions on how
      nurse behaviours facilitate or impede patient experiences of caring. This can
      benefit quality development in clinical practice as being in tune with patient
      experiences and expectations is fundamental to high quality services and patient
      satisfaction.

PMID- 25959521
TI  - Remaining hurdles to effective cancer therapy.

PMID- 25959522
TI  - Towards universal therapeutics for memory disorders.
AB  - Evidence is accumulating that many memory disorders, including those due to
      neurodegenerative diseases, traumatic brain injury (TBI), vascular disease, or
      abnormal brain development, share common features of memory-related pathology.
      Structural and functional deficits of synapses are at the core of the underlying
      pathophysiology, constituting a critical point of convergence in memory
      disorders. Memory therapeutics that target synaptic loss and dysfunction - that
      is, to slow, halt, or reverse progression of the disorders at the level of
      synapses, via synaptogenic molecular cascades such as those of protein kinase C
      (PKC) and brain-derived neurotrophic factor (BDNF) - possess universal
      therapeutic value for many forms of memory disorder. They may be useful either as
      standalone interventions for patients with memory disorders or as adjuncts to
      drugs that target the underlying pathology. 

PMID- 25959523
TI  - Human biomonitoring of phthalate exposure in Austrian children and adults and
      cumulative risk assessment.
AB  - Phthalates are a class of chemicals widely used as plasticisers in a multitude of
      common consumer products. Through contact with such products, people are
      regularly exposed to phthalates, which are suspected to contribute to adverse
      health effects, particularly in the reproductive system. In the present study, 14
      urinary phthalate metabolites of 10 parent phthalates were analysed by HPLC-MS/MS
      among the Austrian population aged 6-15 and 18-81 years in order to assess
      phthalate exposure. In the total study population, ranges of urinary phthalate
      metabolite concentrations were n.d.-2,105 MUg/l (median 25 MUg/l) for monoethyl
      phthalate (MEP), n.d.-88 MUg/l (10 MUg/l) for mono-n-butyl phthalate (MnBP), n.d.
      248 MUg/l (28 MUg/l) for mono-isobutyl phthalate (MiBP), n.d.-57 MUg/l (1.8
      MUg/l) for mono-benzyl phthalate (MBzP), n.d.-20 MUg/l (n.d.) for mono-(2
      ethylhexyl) phthalate (MEHP), n.d.-80 MUg/l (2.6 MUg/l) for mono-(2-ethyl-5
      hydroxyhexyl) phthalate (5OH-MEHP), n.d.-57 MUg/l (1.9 MUg/l) for mono-(2-ethyl-5
      oxohexyl) phthalate (5oxo-MEHP), n.d.-219 MUg/l (11 MUg/l) for mono-(5-carboxy-2
      ethylpentyl) phthalate (5cx-MEPP), n.d.-188 MUg/l (1.6 MUg/l) for 3-carboxy-mono
      proply phthalate (3 cx-MPP), n.d.-5.5 MUg/l (n.d.) for mono-cyclohexyl phthalate
      (MCHP), n.d.-4.5 MUg/l (n.d.) for mono-n-pentyl phthalate (MnPeP), n.d.-3.4 MUg/l
      (n.d.) for mono-n-octyl phthalate (MnOP), n.d.-13 MUg/l (n.d.) for mono-isononyl
      phthalate (MiNP), and n.d.-1.1 MUg/l (n.d.) for mono-isodecyl phthalate (MiDP).
      Generally, children exhibited higher levels of exposure to the majority of
      investigated phthalates, except to MEP, which was found in higher concentrations
      in adults and senior citizens at a maximum concentration of 2,105 MUg/l.
      Individual daily intakes were estimated based on urinary creatinine and urinary
      volume excretion and were then compared to acceptable exposure levels, leading to
      the identification of exceedances of mainly the Tolerable Daily Intakes (TDI),
      especially among children. The execution of a cumulative risk assessment based on
      Hazard Indices showed cause for concern mainly for children, as well as in rare
      cases for adults. Although phthalate exposure seems to have decreased in previous
      years, the wide distribution and existing exceedances of acceptable levels
      indicate that phthalate exposure should be further monitored in order to identify
      exposure sources and enable appropriate minimisation measures.

PMID- 25959524
TI  - Developmental trajectories in cognitive-behavioral phenotypes: Introduction.
AB  - Developmental trajectories in behavioral phenotypes are important areas for
      systematic research and have been for more than 30 years. They interweave several
      important strands related to human growth: that of individuals born with some
      form of intellectual impairment or disability (ID); second, the genetics
      associated with intellectual ability and disability; and third, at the behavioral
      level, the dynamic expression and variability of specific abnormalities as
      individuals age. ID, and the genetic disorders that produce ID, were often not
      well-received by earlier societies. While the inheritance of behavior and
      intellectual ability has probably been observed throughout human history, the
      systematic investigation of the inheritance of intellectual ability probably
      begins with Sir Francis Galton, in his treatise Hereditary Genius in 1869. The
      dynamic features of ID have its roots in late 19th century developmental
      psychology and early 20th century pediatrics. Alfred Binet, along with his
      colleague Theodore Simon, created the first methods of formal intelligence
      testing of children for the French school system. Scores based on the items
      administered would then be used to distinguish children who were prepared for
      enrollment in a standard educational program from those who were not. The
      confluence of these research topics brings us to the subject of our Special
      Issue.

PMID- 25959525
TI  - Drug policy reform and the reclassification of cannabis in England and Wales: A
      cautionary tale.
AB  - When the legal classification of cannabis was downgraded in 2004 it represented
      the most significant liberalisation of British drug law in more than 30 years.
      Paradoxically, however, this apparently progressive reform led to an
      intensification of police efforts targeting minor possession offences and its
      failure was confirmed in January 2009 when the decision to downgrade cannabis was
      reversed. This article documents the impact that reclassification had on law
      enforcement activities and seeks to explain why it failed to deliver a more
      progressive approach. Drawing on official statistics, the analysis charts the
      process of net-widening that followed the reform, identifying a sharp increase in
      the number of people caught in the criminal justice net for minor possession
      offences. While police targeting of such offences was an unintended consequence
      of performance targets, broader political influences were also at play. The
      contradictions and reversals involved in the reclassification of cannabis, it is
      argued, can be readily understood in terms of the broader politics of crime and
      control and the 'structured ambivalence' of state responses. 

PMID- 25959526
TI  - Role of intracellular free calcium in killing Penicillium marneffei within human
      macrophages.
AB  - Increases in cytosolic Ca(2+) concentration ([Ca(2+)]c) promote phagocyte
      antimicrobial responses. Here, we investigated macrophages stimulated by
      Penicillium marneffei (P. marneffei). [Ca(2+)]c was determined in macrophages
      loaded with the fluorescent calcium probe Fura 2/AM as they were stimulated by P.
      marneffei. We found that P. marneffei induced an increase in [Ca(2+)]c in human
      macrophages. Further, increased [Ca(2+)]c with the ionophore A23187 promoted
      phagosomal acidification and maturation and reduced intracellular replication of
      P. marneffei in P. marneffei-infected human macrophages, whereas decreased
      [Ca(2+)]c with the chelation MAPTAM decreased TNF-alpha production, inhibited
      phagosomal acidification and maturation and increased intracellular replication
      of P. marneffei. These data indicate that Ca(2+) signaling may play an important
      role in controlling the replication of P. marneffei within macrophages. 

PMID- 25959527
TI  - Development of a conjugate vaccine against invasive pneumococcal disease based on
      capsular polysaccharides coupled with PspA/family 1 protein of Streptococcus
      pneumoniae.
AB  - The efforts were focused on exploring alternative pneumococcal vaccine
      strategies, aimed at addressing the shortcomings of existing formulations,
      without compromising efficacy. Our strategy involved the use of the carrier
      protein, pneumococcal surface protein A (PspA), conjugated with capsular
      polysaccharides (CPS), to provide effective and non-serotype-dependent
      protection. In this study, we generated a stable Escherichia coli construct
      expressing functional PspA from a capsular serotype 6B strain and confirmed it
      belonging to family 1, which was conjugated with CPS. The distribution of anti
      CPS antibody response was almost completely of IgG2a subclass followed by IgG3
      and low level of IgG1 subclass, but that of anti-PspA IgG subclass antibodies was
      almost equal IgG1 and IgG2a subclasses. Though PspA was less conspicuous on the
      surface of pneumococci than the capsule, the antibodies induced with CPS-rPspA
      conjugate possessed more accessibility to the surface of Streptococcus pneumoniae
      serotype 6B and 19F (the same family 1 PspA). By survival experiment, the result
      suggested that the level of cross-protection after immunized with the conjugate
      was more measurable within the same family 1. The CPS-rPspA conjugate not only
      induced CPS-specific protection but also provided PspA specific cross-protection.

PMID- 25959528
TI  - Cholesterol gallstones and bile host diverse bacterial communities with potential
      to promote the formation of gallstones.
AB  - The prevalence of cholesterol gallstones has increased in recent years. Bacterial
      infection correlates with the formation of gallstones. We studied the composition
      and function of bacterial communities in cholesterol gallstones and bile from 22
      cholesterol gallstone patients using culture-dependent and culture-independent
      methods. Altogether fourteen and eight bacterial genera were detected in
      cholesterol gallstones and bile, respectively. Pseudomonas spp. were the dominant
      bacteria in both cholesterol gallstones and bile. As judged by diversity indices,
      hierarchical clustering and principal component analysis, the bacterial
      communities in gallstones were different from those in bile. The gallstone
      microbiome was considered more stable than that of bile. The different microbial
      communities may be partially explained by differences in their habitats. We found
      that 30% of the culturable strains from cholesterol gallstones secreted beta
      glucuronidase and phospholipase A2. Pseudomonas aeruginosa strains showed the
      highest beta-glucuronidase activity and produced the highest concentration of
      phospholipase A2, indicating that Ps. aeruginosa may be a major agent in the
      formation of cholesterol gallstones. 

PMID- 25959529
TI  - Effect of pioglitazone on plasma ceramides in adults with metabolic syndrome.
AB  - BACKGROUND: Metabolic syndrome (MetS) appears closely linked with ceramide
      accumulation, inducing insulin resistance and toxicity to multiple cell types.
      Animal studies demonstrate that thiazolidinediones (TZDs) reduce ceramide
      concentrations in plasma and skeletal muscle and support lowering of ceramide
      levels as a potential mediator of TZDs' mechanism of action in reducing insulin
      resistance; however, studies in humans have yet to be reported. This study
      investigated the effects of pioglitazone therapy on plasma ceramides to
      understand the mechanism by which TZDs improve insulin resistance in MetS.
      METHODS: Thirty-seven subjects with MetS were studied in a single-centre,
      randomized, double-blind, placebo-controlled trial comparing pioglitazone to
      placebo. Data were collected at baseline and after 6 months of therapy. The
      primary endpoint was the change from baseline in plasma ceramide concentrations.
      RESULTS: Treatment with pioglitazone for 6 months, compared with placebo,
      significantly reduced multiple plasma ceramide concentrations: C18:0 (p = 0.001),
      C20:0 (p = 0.0004), C24 : 1 (p = 0.009), dihydroceramide C18 :0 (p = 0.005),
      dihydroceramide C24:1 (p = 0.004), lactosylceramide C16:0 (p = 0.02) and the
      hexosylceramides C16:0 (p = 0.0003), C18 : 0 (p = 0.00001), C22:0 (p = 0.00002)
      and C24:1 (p = 0.0006). Additionally, significant reductions were found when
      ceramides were grouped by species: ceramides (p = 0.03), dihydroceramides (p =
      0.02), hexosylceramides (p = 0.00001) and lactosylceramides (p = 0.02). The total
      of all measured ceramides was also significantly reduced (p = 0.001). Following
      treatment with pioglitazone, the decrease in some ceramide species correlated
      negatively with the change in insulin sensitivity (dihydroceramide C16:0, r = 
      0.54; p = 0.02) and positively with total (lactosylceramide C24:0, r = 0.53; p =
      0.02) and high molecular weight (lactosylceramide C24:0, r = 0.48; p = 0.05)
      adiponectin measurements; however, significant associations with changes in liver
      fat and glycemic control reduction were not found. CONCLUSIONS: Pioglitazone in
      individuals with MetS induces a potent decrease in plasma ceramides, and some of
      the changes correlate with changes in insulin resistance and adiponectin levels.

PMID- 25959530
TI  - Axillary lymphatic malformations: Prenatal evaluation and postnatal outcomes.
AB  - BACKGROUND/PURPOSE: The purpose of this study is to describe the prenatal
      findings and postnatal outcomes of fetuses with axillary lymphatic malformations.
      METHODS: Retrospective chart review of fetuses with the prenatal diagnosis of
      isolated axillary lymphatic malformation detected between 2009 and 2013. RESULTS:
      There were 8 fetuses diagnosed with isolated axillary lymphatic malformation.
      Median gestational age at diagnosis was 20.5 (19-28) weeks. All fetuses were
      evaluated by serial ultrasound and ultrafast fetal MRI. Two pregnancies were
      electively terminated. All continued pregnancies reached term, and all fetuses
      were delivered by cesarean section. None of the fetuses developed polyhydramnios
      or hydrops fetalis. Only one patient had an associated malformation (coarctation
      of the aorta). All patients were evaluated postnatally by MRI. Treatment included
      sclerotherapy only (1), sclerotherapy followed by surgical resection (1),
      surgical resection only (3), and observation (1). The median postnatal hospital
      stay was 8 (6-15) days. Three cases recurred after the initial treatment, two
      after surgery and one after sclerotherapy. On a median follow up of 2.1 years,
      all patients have some degree of visible residual disease. There were no deaths.
      CONCLUSIONS: Prenatal diagnosis of axillary lymphatic malformation is increasing
      with improved technology. Axillary lymphatic malformations are usually isolated
      developmental anomalies that do not affect fetal health. Postnatal management
      options include surgery, sclerotherapy, and observation. Recurrences and residual
      disease after all types of treatment are frequent. This should be communicated to
      the parents at the time of prenatal counseling.

PMID- 25959531
TI  - A quantification of the relationship between neuronal responses in the rat
      rostral ventromedial medulla and noxious stimulation-evoked withdrawal reflexes.
AB  - The rostral ventromedial medulla (RVM) regulates a range of involuntary
      behaviours but is most often associated with nociception via the action of
      pronociceptive ON cells and antinociceptive OFF cells. The phasic responses of ON
      and OFF cells determine whether or not incoming noxious signals provoke a
      withdrawal reflex, and previous studies have suggested that reflex RVM activity
      patterns actively shape motor output. Here we challenged the model by using
      juvenile rats, which are known to exhibit markedly different reflex responses
      compared with adults. By recording single-cell activity in the RVM and the
      electromyography responses of hindlimb flexor muscles to noxious thermal
      stimulation we found that the juvenile reflex had a shorter onset latency, was
      larger in amplitude and exhibited a decreased rise time compared with the adult
      reflex. The responses of ON and OFF cells faithfully tracked the shorter onset
      latency of the reflex by also responding earlier and, thus, still preceded the
      reflex. However, neither the reflex amplitude nor the ongoing response profile
      was predicted by the firing rate of RVM cells in either age group. Instead we
      found a close correspondence between RVM activity and the reflex only during the
      initiation of the response. Furthermore, the short rise time of the juvenile
      reflex was reflected in higher rates of change of both ON and OFF cell firing.
      Our data suggest that the RVM is associated only with the initiation of reflexes
      and does not shape ongoing muscle activity, which is more likely to be subserved
      by downstream spinal processes. 

PMID- 25959533
TI  - Target DNA induced switches of DNA polymerase activity.
AB  - A novel concept that target DNA can induce switching of DNA polymerase activity
      is devised. The method relies on the finding that a DNA aptamer can undergo
      conformational change upon hybridization with a complementary target DNA, which
      leads to activation or inactivation of DNA polymerase. This strategy is utilized
      to identify the presence of target DNA with high levels of sensitivity and
      selectivity. 

PMID- 25959535
TI  - A low-surface energy carbon allotrope: the case for bcc-C6.
AB  - Graphite may be viewed as a low-surface-energy carbon allotrope with little layer
      layer interaction. Other low-surface-energy allotropes but with much stronger
      layer-layer interaction may also exist. Here, we report a first-principles
      prediction for one of the known carbon allotropes, bcc-C6 (a body centered carbon
      allotrope with six atoms per primitive unit), that should have exceptionally low
      surface energy and little size dependence down to only a couple layer thickness.
      This unique property may explain the existence of the relatively-high-energy bcc
      C6 during growth. The electronic properties of the bcc-C6 thin layers can also be
      intriguing: the (111), (110), and (001) thin layers have direct band gap,
      indirect band gap, and metallic character, respectively. The refrained chemical
      reactivity of the thin layers does not disappear after cleaving, as lithium-doped
      (Li-doped) 3-layers (111) has a noticeably increased binding energy of H2
      molecules with a maximum storage capacity of 10.8 wt%. 

PMID- 25959534
TI  - Cytochrome P450-mediated warfarin metabolic ability is not a critical determinant
      of warfarin sensitivity in avian species: In vitro assays in several birds and in
      vivo assays in chicken.
AB  - Coumarin-derivative anticoagulant rodenticides used for rodent control are posing
      a serious risk to wild bird populations. For warfarin, a classic coumarin
      derivative, chickens have a high median lethal dose (LD50), whereas mammalian
      species generally have much lower LD50. Large interspecies differences in
      sensitivity to warfarin are to be expected. The authors previously reported
      substantial differences in warfarin metabolism among avian species; however, the
      actual in vivo pharmacokinetics have yet to be elucidated, even in the chicken.
      In the present study, the authors sought to provide an in-depth characterization
      of warfarin metabolism in birds using in vivo and in vitro approaches. A kinetic
      analysis of warfarin metabolism was performed using liver microsomes of 4 avian
      species, and the metabolic abilities of the chicken and crow were much higher in
      comparison with those of the mallard and ostrich. Analysis of in vivo metabolites
      from chickens showed that excretions predominantly consisted of 4'
      hydroxywarfarin, which was consistent with the in vitro results. Pharmacokinetic
      analysis suggested that chickens have an unexpectedly long half-life despite
      showing high metabolic ability in vitro. The results suggest that the half-life
      of warfarin in other bird species could be longer than that in the chicken and
      that warfarin metabolism may not be a critical determinant of species differences
      with respect to warfarin sensitivity.

PMID- 25959536
TI  - Fighting microbial infections: A lesson from amphibian skin-derived esculentin-1
      peptides.
AB  - Due to the growing emergence of resistance to commercially available
      antibiotics/antimycotics in virtually all clinical microbial pathogens, the
      discovery of alternative anti-infective agents, is greatly needed. Gene-encoded
      antimicrobial peptides (AMPs) hold promise as novel therapeutics. In particular,
      amphibian skin is one of the richest storehouses of AMPs, especially that of the
      genus Rana, with esculentins-1 being among the longest (46 amino acids) AMPs
      found in nature to date. Here, we report on the recently discovered in vitro and
      in vivo activities and mechanism of action of two derivatives of the N-terminal
      part of esculentin-1a and -1b peptides, primarily against two relevant
      opportunistic microorganisms causing a large number of life-threatening
      infections worldwide; i.e. the Gram-negative bacterium Pseudomonas aeruginosa and
      the yeast Candida albicans. Because of distinct advantages compared to several
      mammalian AMPs, the two selected frog skin AMP-derivatives represent attractive
      candidates for the development of new antimicrobial compounds with expanded
      properties, for both human and veterinary medicine. 

PMID- 25959538
TI  - The activity of the nonsulfated sulfakinin Zopat-SK-1 in the neck-ligated larvae
      of the beetle Zophobas atratus.
AB  - Insect sulfakinins (SKs) are multifunctional neuropeptides structurally and
      functionally homologous to the mammalian gastrin/cholecystokinin (CCK). It has
      been proposed that SKs play a role in modulating energy management in insects by
      interacting with adipokinetic hormone (AKH), the principle hormone controlling
      insect intermediary metabolism. To exclude head factors (including AKH) that
      influence the activity of the nonsulfated sulfakinin Zopat-SK-1 in the larvae of
      the beetle Zophobas atratus, ligature and in vitro bioassays were used. Our study
      showed that in the neck-ligated larvae, Zopat-SK-1 evoked a much more pronounced
      glycogenolytic effect in fat body tissue and a significantly higher
      hypertrahelosemic effect in hemolymph than in larvae without ligation. We found
      that the concentration of the sugar trehalose increased under hormonal treatment
      but no changes in glucose levels were observed. Under in vitro conditions, the
      maximal glycogenolytic effect of Zopat-SK-1 in fat body was observed at 10 pmol
      of hormone. Ligature and in vitro bioassays indicated that Zopat-SK-1 activity in
      the Z. atratus larvae is modulated by head signals and/or factors from the
      gastrointestinal tract. Our data indicate the existence of a brain
      gastrointestinal axis that has a role in controlling of energy (carbohydrate)
      metabolism in the insect body. Moreover, these results, together with
      immunological evidence of a cholecystokinin-like (sulfakinin) receptor in the Z.
      atratus fat body, help us to better understand the SK signaling pathways and its
      physiological role in insect biology.

PMID- 25959537
TI  - Brain kinin B1 receptor is upregulated by the oxidative stress and its activation
      leads to stereotypic nociceptive behavior in insulin-resistant rats.
AB  - Kinin B1 receptor (B1R) is virtually absent under physiological condition, yet it
      is highly expressed in models of diabetes mellitus. This study aims at
      determining: (1) whether B1R is induced in the brain of insulin-resistant rat
      through the oxidative stress; (2) the consequence of B1R activation on
      stereotypic nocifensive behavior; (3) the role of downstream putative mediators
      in B1R-induced behavioral activity. Sprague-Dawley rats were fed with 10% D
      glucose in their drinking water or tap water (controls) for 4 or 12 weeks,
      combined either with a standard chow diet or a diet enriched with alpha-lipoic
      acid (1 g/kg feed) for 4 weeks. The distribution and density of brain B1R binding
      sites were assessed by autoradiography. Behavioral activity evoked by i.c.v.
      injection of the B1R agonist Sar-[D-Phe(8)]-des-Arg(9)-BK (10 MUg) was measured
      before and after i.c.v. treatments with selective antagonists (10 MUg) for kinin
      B1 (R-715, SSR240612), tachykinin NK1 (RP-67580) and glutamate NMDA (DL-AP5)
      receptors or with the inhibitor of NOS (L-NNA). Results showed significant
      increases of B1R binding sites in various brain areas of glucose-fed rats that
      could be prevented by the diet containing alpha-lipoic acid. The B1R agonist
      elicited head scratching, grooming, sniffing, rearing, digging, licking, face
      washing, wet dog shake, teeth chattering and biting in glucose-fed rats, which
      were absent after treatment with alpha-lipoic acid or antagonists/inhibitors.
      Data suggest that kinin B1R is upregulated by the oxidative stress in the brain
      of insulin-resistant rats and its activation causes stereotypic nocifensive
      behavior through the release of substance P, glutamate and NO.

PMID- 25959539
TI  - Oxidative stress in benign prostate hyperplasia.
AB  - To assess the status of oxidative stress in benign prostate hyperplasia, a very
      common disease in older men which constitutes a public health problem in Jijel,
      prostate tissues were obtained by transvesical adenomectomy from 10 men with
      benign prostate hyperplasia. We measured the cytosolic levels of malondialdehyde
      (MDA) and glutathione (GSH) and cytosolic enzyme activities of superoxide
      dismutase, catalase, glutathione peroxidase and glutathione S-transferase. The
      development of benign prostate hyperplasia is accompanied by impaired oxidative
      status by increasing levels of MDA, depletion of GSH concentrations and a
      decrease in the activity of all the antioxidant enzymes studied. These results
      have allowed us to understand a part of the aetiology of benign prostate
      hyperplasia related to oxidative stress. 

PMID- 25959540
TI  - Corannulene Molecular Rotor with Flexible Perfluorobenzyl Blades: Synthesis,
      Structure and Properties.
AB  - Two members of a new class of organic-acceptor perfluorobenzyl corannulenes were
      prepared by gas-phase and highly-selective solution-phase reactions at elevated
      temperatures. The peculiar single-crystal X-ray structure of C5-C20H5(CF2C6F5)5
      revealed two high-energy conformers with drastically different bowl depths and
      orientations of perfluorobenzyl blades; the conformers are alternating in
      columnar packing arrangements and every pair is sandwiched by toluene molecules.

PMID- 25959541
TI  - Multilocus sequence analysis (MLSA) in prokaryotic taxonomy.
AB  - To obtain a higher resolution of the phylogenetic relationships of species within
      a genus or genera within a family, multilocus sequence analysis (MLSA) is
      currently a widely used method. In MLSA studies, partial sequences of genes
      coding for proteins with conserved functions ('housekeeping genes') are used to
      generate phylogenetic trees and subsequently deduce phylogenies. However, MLSA is
      not only suggested as a phylogenetic tool to support and clarify the resolution
      of bacterial species with a higher resolution, as in 16S rRNA gene-based studies,
      but has also been discussed as a replacement for DNA-DNA hybridization (DDH) in
      species delineation. Nevertheless, despite the fact that MLSA has become an
      accepted and widely used method in prokaryotic taxonomy, no common generally
      accepted recommendations have been devised to date for either the whole area of
      microbial taxonomy or for taxa-specific applications of individual MLSA schemes.
      The different ways MLSA is performed can vary greatly for the selection of genes,
      their number, and the calculation method used when comparing the sequences
      obtained. Here, we provide an overview of the historical development of MLSA and
      critically review its current application in prokaryotic taxonomy by highlighting
      the advantages and disadvantages of the method's numerous variations. This
      provides a perspective for its future use in forthcoming genome-based genotypic
      taxonomic analyses. 

PMID- 25959542
TI  - Study of three non-syndromic cases of congenital thumb aplasia in captive rhesus
      monkeys.
AB  - Although congenital thumb absence has been reported frequently in humans, their
      occurrence in macaques is rare. We observed three cases of spontaneous thumb
      defects in captive female rhesus monkeys. One animal exhibited bilateral absence
      and two other presented unilateral thumb absence, all with metacarpal integrity.
      This report presents the clinical, radiological, and genealogical details as well
      as possible etiologies in an attempt to draw a parallel with humans and other
      primate species. 

PMID- 25959544
TI  - Direct Synthesis of 5-Aryl Barbituric Acids by Rhodium(II)-Catalyzed Reactions of
      Arenes with Diazo Compounds.
AB  - A commercially available rhodium(II) complex catalyzes the direct arylation of 5
      diazobarbituric acids with arenes, allowing straightforward access to 5-aryl
      barbituric acids. Free N-H groups are tolerated on the barbituric acid, with no
      complications arising from N-H insertion processes. This method was applied to
      the concise synthesis of a potent matrix metalloproteinase (MMP) inhibitor.

PMID- 25959543
TI  - Comparing clinical outcomes in HIV-infected and uninfected older men hospitalized
      with community-acquired pneumonia.
AB  - OBJECTIVES: Outcomes of community-acquired pneumonia (CAP) among HIV-infected
      older adults are unclear. METHODS: Associations between HIV infection and three
      CAP outcomes (30-day mortality, readmission within 30 days post-discharge, and
      hospital length of stay [LOS]) were examined in the Veterans Aging Cohort Study
      (VACS) of male Veterans, age >= 50 years, hospitalized for CAP from 10/1/2002
      through 08/31/2010. Associations between the VACS Index and CAP outcomes were
      assessed in multivariable models. RESULTS: Among 117 557 Veterans (36 922 HIV
      infected and 80 635 uninfected), 1203 met our eligibility criteria. The 30-day
      mortality rate was 5.3%, the mean LOS was 7.3 days, and 13.2% were readmitted
      within 30 days of discharge. In unadjusted analyses, there were no significant
      differences between HIV-infected and uninfected participants regarding the three
      CAP outcomes (P > 0.2). A higher VACS Index was associated with increased 30-day
      mortality, readmission, and LOS in both HIV-infected and uninfected groups.
      Generic organ system components of the VACS Index were associated with adverse
      CAP outcomes; HIV-specific components were not. Among HIV-infected participants,
      those not on antiretroviral therapy (ART) had a higher 30-day mortality (HR 2.94
      [95% CI 1.51, 5.72]; P = 0.002) and a longer LOS (slope 2.69 days [95% CI 0.65,
      4.73]; P = 0.008), after accounting for VACS Index. Readmission was not
      associated with ART use (OR 1.12 [95% CI 0.62, 2.00] P = 0.714). CONCLUSION:
      Among HIV-infected and uninfected older adults hospitalized for CAP, organ system
      components of the VACS Index were associated with adverse CAP outcomes. Among HIV
      infected individuals, ART was associated with decreased 30-day mortality and LOS.

PMID- 25959545
TI  - SVSI: fast and powerful set-valued system identification approach to identifying
      rare variants in sequencing studies for ordered categorical traits.
AB  - In genetic association studies of an ordered categorical phenotype, it is usual
      to either regroup multiple categories of the phenotype into two categories and
      then apply the logistic regression (LG), or apply ordered logistic (oLG), or
      ordered probit (oPRB) regression, which accounts for the ordinal nature of the
      phenotype. However, they may lose statistical power or may not control type I
      error due to their model assumption and/or instable parameter estimation
      algorithm when the genetic variant is rare or sample size is limited. To solve
      this problem, we propose a set-valued (SV) system model to identify genetic
      variants associated with an ordinal categorical phenotype. We couple this model
      with a SV system identification algorithm to identify all the key system
      parameters. Simulations and two real data analyses show that SV and LG accurately
      controlled the Type I error rate even at a significance level of 10(-6) but not
      oLG and oPRB in some cases. LG had significantly less power than the other three
      methods due to disregarding of the ordinal nature of the phenotype, and SV had
      similar or greater power than oLG and oPRB. We argue that SV should be employed
      in genetic association studies for ordered categorical phenotype. 

PMID- 25959546
TI  - Iliorenal periscope graft to maintain blood flow to accessory renal artery.
AB  - Parallel endografts such as "chimney" and "periscope" are being increasingly used
      to maintain blood flow to visceral and supra-aortic branches in patients with
      different aortic disorders. We present a new technique, "iliorenal periscope
      graft", in a patient with abdominal aortic aneurysm undergoing endovascular
      aortic repair. In this case, left accessory renal artery flows were provided by
      an iliorenal periscope graft that extends from the left accessory renal artery to
      the right common iliac artery in a retrograde fashion. 

PMID- 25959547
TI  - Is interaction of amyloid beta-peptides with metals involved in cognitive
      activity?
AB  - Metal ions, i.e., Zn(2+) and Cu(2+), are released from neuron terminals in the
      hippocampus, which plays important roles in spatial and declarative memory, and
      may serve as a signal factor. Synaptic homeostasis of metal ions is critical for
      cognitive activity in the hippocampus. Amyloid-beta (Abeta) is a causative
      candidate for the pathogenesis of Alzheimer's disease (AD) and Abeta-induced
      synapse dysfunction is easy to emerge along with normal aging and leads to the
      cognitive decline and memory loss in the pre-dementia stage of AD. Because Abeta
      interacts with Zn(2+) and Cu(2+), it is likely that these metal ions are involved
      in the Abeta-induced modification of the synaptic function. There is evidence to
      indicate that the inhibition of the interaction of Abeta with Zn(2+) and Cu(2+)
      may ameliorate the pathophysiology of AD. Interaction of extracellular Zn(2+)
      with Abeta in the hippocampus is involved in transiently Abeta-induced cognition
      deficits, while the interaction of extracellular Cu(2+) reduces bioavailability
      of intracellular Cu(2+), followed by an increase in oxidative stress, which may
      lead to cognitive deficits. It is likely that Zn(2+) and Cu(2+) play as a key
      mediating factor in pathophysiology of the synaptic dysfunction in which Abeta is
      involved. Based on the idea that understating Abeta-induced changes in synaptic
      plasticity is important to prevent AD, the present paper summarizes the
      interaction of Abeta with metal ions in cognition. 

PMID- 25959548
TI  - Valvular Regurgitation Using Portable Echocardiography in a Healthy Student
      Population: Implications for Rheumatic Heart Disease Screening.
AB  - BACKGROUND: There is increasing use of portable echocardiography as a screening
      test for rheumatic heart disease (RHD). The prevalence of valvular regurgitation
      in healthy populations as determined using portable echocardiography has not been
      well defined. Minimal echocardiographic criteria for RHD have recently been
      clarified, but the overlap of normal and abnormal valvular regurgitation warrants
      further study. The aim of this study was to determine the spectrum of
      echocardiographic findings using portable echocardiography in children from a
      population with low prevalence of RHD. METHODS: Screening echocardiography was
      conducted in 396 healthy students aged 10 to 12 years using portable
      echocardiographic equipment. Echocardiograms were assessed according to 2012
      World Heart Federation criteria for RHD. The prevalence of physiologic valvular
      regurgitation was compared with that found in previous studies of children using
      large-platform machines. RESULTS: Physiologic mitral regurgitation (MR) was
      present in 14.9% of subjects (95% CI, 11.7%-18.7%) and pathologic MR in 1.3% (95%
      CI, 0.6%-2.9%). Two percent (95% CI, 1.0%-3.9%) had physiologic aortic
      regurgitation, and none had pathologic aortic valve regurgitation. Physiologic
      tricuspid regurgitation was present in 72.7% of subjects (95% CI, 68.1%-76.9%)
      and physiologic pulmonary regurgitation in 89.6% (95% CI, 85.7%-91.8%). After
      cardiology review, no cases of definite RHD were found, but 0.5% of patients (95%
      CI, 0.1%-1.8%) had pathologic MR meeting World Heart Federation criteria for
      borderline RHD. Two percent (95% CI, 1.4%-4.6%) of the cohort had minor forms of
      congenital heart disease. CONCLUSIONS: The spectrum of physiologic cardiac
      valvular regurgitation in healthy children as determined using portable
      echocardiography is described and is within the range of previous studies using
      large-platform echocardiographic equipment. The finding of two children with
      pathologic-grade MR, likely representing the upper limit of physiologic
      regurgitation, has implications for echocardiographic screening for RHD in high
      prevalence regions.

PMID- 25959550
TI  - Maternal nutrition in pregnancy and metabolic risks among neonates in a Pakistani
      population, a pilot study.
AB  - The aim of this study was to observe the association between maternal
      undernutrition and metabolic risk indicators in newborns at birth. Fifty-nine
      expectant mothers between 28 and 40 weeks of gestation were included after
      obtaining their informed consent. Mothers were divided into undernourished,
      normally nourished and overnourished groups. A total of 54 deliveries were
      followed-up, and cord blood samples were collected. Metabolic status at birth was
      assessed by determining the cord blood concentrations of glucose, insulin and
      lipids and by measuring insulin resistance through homeostasis model assessment.
      Metabolic risk indicators in the offspring were compared following mothers'
      nutrition status (under and normal nourished groups). We found that
      concentrations of glucose (5.31+/-2.01 v. 4.69+/-2.22 mmol/l, P=0.01), total
      cholesterol (2.51+/-1.52 v. 1.84+/-0.66 mmol/l, P=0.04), triglycerides (0.85+/
      1.12 v. 0.34+/-0.24 mmol/l, P=0.00) and low-density lipoprotein (LDL)-cholestrol
      (1.26+/-0.93 v. 1.02+/-0.50 mmol/l, P=0.04) were significantly high in the
      offspring born to undernourished mothers. LDL-cholestrol remained significantly
      high in the undernourished group even after adjustment for potential confounders.
      Furthermore, a weak association was observed between maternal body fat mass with
      serum leptin (r=0.272, P=0.05) and maternal body mass Index with LDL-cholestrol
      in the cord blood (r=0.285, P=0.05). Our results showed that offspring of
      undernourished mothers had a relatively higher metabolic risk profile including
      LDL-cholestrol compared with normal nourished group, suggesting that maternal
      undernutrition may influence metabolic risk markers of the newborn at birth. We
      recommend that these results should be confirmed by a longitudinal study with a
      larger sample size. 

PMID- 25959549
TI  - Clinical utility of subtyping binge eating disorder by history of anorexia or
      bulimia nervosa in a treatment sample.
AB  - OBJECTIVE: This study examined whether having a history of anorexia nervosa (AN)
      or bulimia nervosa (BN) is associated with response to treatment in adults with
      binge eating disorder (BED). METHOD: Data from 189 adults diagnosed with BED who
      were randomly assigned to one of three group cognitive-behavioral (CBT)
      treatments were analyzed to compare those with and without a history of AN/BN.
      RESULTS: A total of 16% of the sample had a history of AN/BN. The BED subgroup
      with a history of AN/BN presented with higher rates of mood disorders and greater
      eating-related symptom severity at baseline. Participants with a history of AN/BN
      also had higher global eating disorder (ED) symptoms at end of treatment (EOT),
      and more frequent objective binge-eating episodes at EOT and 12-month follow-up.
      DISCUSSION: These findings suggest that in adults with BED, a history of AN/BN is
      predictive of greater eating-related symptom severity following group-based CBT
      and poorer short- and long-term binge-eating outcomes. These findings suggest
      that considering ED history in the treatment of adults with BED may be clinically
      useful.

PMID- 25959551
TI  - Ascosphaera apis, the entomopathogenic fungus affecting larvae of native bees
      (Xylocopa augusti): First report in South America.
AB  - BACKGROUND: Nowadays several invertebrate pollinators of crops and wild plants
      are in decline as result of multiple and, sometimes, unknown factors; among them,
      the modern agricultural practices, pests and diseases are postulated as the most
      important factors. Bees of the genus Xylocopa are considered effective
      pollinators of passion fruit crops in tropical regions, as well as important
      pollinators in wild plants, but these bees are attacked by several pathogens that
      affect different stages in their life cycle. The fungal species of the genus
      Ascosphaera are commonly associated with social and solitary bee larvae causing
      chalkbrood disease. AIMS: The aim of the present study was to demonstrate the
      presence of Ascosphaera apis affecting larvae of Xylocopa augusti in South
      America. METHODS: For this purpose, A. apis was isolated from affected larvae in
      YGPSA medium. Final identification was run out by three techniques: (1)
      Microscopic examination of the hyphae and sizes of the fruiting bodies; (2)
      Mating test, and specific sexual compatibility test, and (3) PCR detection, using
      specific primers. RESULTS: This study demonstrates for the first time the
      presence of A. apis affecting larvae of X. augusti in South America. CONCLUSIONS:
      The evidence of A. apis affecting the larvae of X. augusti, and the fact that the
      sharing of pathogens between different bee species has been underestimated,
      suggests the need for further epidemiological studies in order to determine not
      only the prevalence of this pathogen among wild pollinators, but also its
      relationship to the sudden collapse of honey bee colonies in this region.

PMID- 25959552
TI  - Template-free construction of hollow alpha-Fe2O3 hexagonal nanocolumn particles
      with an exposed special surface for advanced gas sensing properties.
AB  - Hollow alpha-Fe2O3 hexagonal nanocolumn particles (HHCPs) with exposed
      (101[combining macron]0) and (112[combining macron]5) facets have been
      synthesized through a hydrothermal method in the absence of templates. The time
      dependent experimental results demonstrate that the formation of HHCPs includes
      four main steps: (1) formation of nanowire precursors, (2) aggregation and
      conversion to Fe1.833(OH)0.5O2 solid ellipsoid particles (SEPs), (3) dehydration
      to form hollow ellipsoid particles (HEPs), and (4) recrystallization to HHCPs.
      Due to their advantages of the hollow structure and the exposed special external
      and internal surface on the pore structure, the HHCPs exhibit higher gas sensing
      ability than that of calcined SEPs (CSEPs) and HEPs. 

PMID- 25959553
TI  - The rationale for liquid biopsy in colorectal cancer: a focus on circulating
      tumor cells.
AB  - Capturing circulating tumor cells (CTCs) and/or circulating tumor DNA from blood,
      which represents a precious source of biological material derived from both
      primary and metastatic tumors, has been named a 'liquid biopsy'. While the
      circulating tumor DNA might be more representative of the bulk of the metastatic
      tumor, CTCs are thought to reflect more of the metastases-initiating cells.
      Consequently, a liquid biopsy made of tumor cells and tumor DNA that is able to
      track cancer evolution, as a fingerprint of the patient's individual tumor, and
      is easy to perform at every stage of the disease course, sounds attractive. This
      article mainly focuses on the applications of CTCs to track tumor dynamics in
      real time using colorectal cancer as a model system. The analysis of viable CTCs
      at DNA, RNA and protein levels, as well as their expansion in vitro, may allow
      deep investigation of the features of metastases-initiating cells. 

PMID- 25959554
TI  - Extracting features buried within high density atom probe point cloud data
      through simplicial homology.
AB  - Feature extraction from Atom Probe Tomography (APT) data is usually performed by
      repeatedly delineating iso-concentration surfaces of a chemical component of the
      sample material at different values of concentration threshold, until the user
      visually determines a satisfactory result in line with prior knowledge. However,
      this approach allows for important features, buried within the sample, to be
      visually obscured by the high density and volume (~10(7) atoms) of APT data. This
      work provides a data driven methodology to objectively determine the appropriate
      concentration threshold for classifying different phases, such as precipitates,
      by mapping the topology of the APT data set using a concept from algebraic
      topology termed persistent simplicial homology. A case study of Sc precipitates
      in an Al-Mg-Sc alloy is presented demonstrating the power of this technique to
      capture features, such as precise demarcation of Sc clusters and Al segregation
      at the cluster boundaries, not easily available by routine visual adjustment. 

PMID- 25959556
TI  - Breast conserving therapy or mastectomy: a done deal or one worth returning to?

PMID- 25959557
TI  - Development of a dual-protective live attenuated vaccine against H5N1 and H9N2
      avian influenza viruses by modifying the NS1 gene.
AB  - An increasing number of outbreaks of avian influenza H5N1 and H9N2 viruses in
      poultry have caused serious economic losses and raised concerns for human health
      due to the risk of zoonotic transmission. However, licensed H5N1 and H9N2
      vaccines for animals and humans have not been developed. Thus, to develop a dual
      H5N1 and H9N2 live-attenuated influenza vaccine (LAIV), the HA and NA genes from
      a virulent mouse-adapted avian H5N2 (A/WB/Korea/ma81/06) virus and a recently
      isolated chicken H9N2 (A/CK/Korea/116/06) virus, respectively, were introduced
      into the A/Puerto Rico/8/34 backbone expressing truncated NS1 proteins (NS1-73,
      NS1-86, NS1-101, NS1-122) but still possessing a full-length NS gene. Two
      H5N2/NS1-LAIV viruses (H5N2/NS1-86 and H5N2/NS1-101) were highly attenuated
      compared with the full-length and remaining H5N2/NS-LAIV viruses in a mouse
      model. Furthermore, viruses containing NS1 modifications were found to induce
      more IFN-beta activation than viruses with full-length NS1 proteins and were
      correspondingly attenuated in mice. Intranasal vaccination with a single dose
      (10(4.0) PFU/ml) of these viruses completely protected mice from a lethal
      challenge with the homologous A/WB/Korea/ma81/06 (H5N2), heterologous highly
      pathogenic A/EM/Korea/W149/06 (H5N1), and heterosubtypic highly virulent mouse
      adapted H9N2 viruses. This study clearly demonstrates that the modified H5N2/NS1
      LAIV viruses attenuated through the introduction of mutations in the NS1 coding
      region display characteristics that are desirable for live attenuated vaccines
      and hold potential as vaccine candidates for mammalian hosts. 

PMID- 25959555
TI  - Subclinical kidney injury before and 1 year after bariatric surgery among
      adolescents with severe obesity.
AB  - OBJECTIVE: To assess subclinical kidney injury in adolescents with severe obesity
      by measuring biomarkers of early kidney disease and to assess changes in the
      levels of these biomarkers following bariatric procedures. METHODS: Twenty-two
      adolescents undergoing bariatric surgery with no microalbuminuria and normal
      kidney function were selected. Urinary NGAL, IL-18, and KIM-1 were measured at
      baseline, 6 and 12 months postoperatively. Biomarker levels were compared to 44
      age-gender-matched lean controls. RESULTS: Subjects with obesity had a mean
      baseline BMI of 48 kg/m(2) that decreased by 34% at 1-year follow-up. Urine NGAL,
      IL-18, and KIM-1 were significantly elevated in subjects with obesity compared to
      lean controls at baseline. The obese cohort had a further significant increase in
      NGAL and KIM-1 at 6 months, followed by decline at 1 year. The overall change in
      levels of all three biomarkers through 1 year after surgery, however, was not
      significant compared to baseline. CONCLUSIONS: Adolescent severe obesity is
      associated with increased urinary excretion of novel biomarkers of kidney injury,
      despite no microalbuminuria or decreased kidney function. This subclinical kidney
      injury persists 1 year after significant weight loss induced by bariatric
      surgery, suggesting that close, long-term follow-up of kidney status is warranted
      in these adolescents.

PMID- 25959558
TI  - Comparison of Prasugrel and Ticagrelor Antiplatelet Effects in Korean Patients
      Presenting With ST-Segment Elevation Myocardial Infarction.
AB  - BACKGROUND: There is insufficient data on the efficacy of prasugrel and
      ticagrelor in Korean patients with ST-segment elevation myocardial infarction
      (STEMI). METHODS AND RESULTS: I n the current double-blind, prospective pilot
      study, 39 patients with STEMI undergoing primary percutaneous coronary
      intervention were randomized to receive prasugrel 60 mg loading dose (LD)
      followed by 10 mg daily maintenance dose (n=19), or ticagrelor 180 mg LD followed
      by 90 mg twice daily maintenance dose (n=20). We assessed platelet reactivity
      with the VerifyNow and Vasodilator-Stimulated Phosphoprotein (VASP) P2Y12 assays.
      Compared to baseline platelet reactivity, both prasugrel and ticagrelor groups
      achieved similar and significantly lower P2Y12 reaction units (PRU) (259 [IQR:
      230 to 281] vs. 28 [12 to 55] for prasugrel; 261 [196 to 286] vs. 43 [11 to 61]
      for ticagrelor), and platelet reactivity indexes (PRI) (51.2% [39.3 to 61.3] vs.
      8.1% [6.1 to 14.7] for prasugrel; 47.5% [38.4 to 50.4] vs. 11.2% [7.1 to 15.5]
      for ticagrelor, all P values <0.001) at 48 h post-LD. Most patients had low
      platelet reactivity with 95% PRU values <85 and 82% with PRI <16%. CONCLUSIONS:
      Both prasugrel and ticagrelor were effective for platelet inhibition in Korean
      STEMI patients with almost no patients exhibiting high platelet reactivity at 48
      h after the LD. Our finding of a high number of patients with very low platelet
      reactivity deserves further studies to assess the safety of the drugs (Prasugrel
      and Ticagrelor in ST-segment Elevation Myocardial Infarction Study, NCT02075125).

PMID- 25959559
TI  - Report of the American College of Cardiology (ACC) Scientific Sessions 2015, San
      Diego.
AB  - The 64th Annual Scientific Sessions and Exposition of the American College of
      Cardiology (ACC) were held at the San Diego Convention Center from March 14-16,
      2015. The ACC Scientific Sessions are 1 of 2 major scientific cardiology meetings
      in the United States, with nearly 20,000 attendees, including 15,000
      cardiovascular professionals. There were over 2,100 oral and poster abstracts,
      and more than 15 late-breaking clinical trials (LBCTs) abstructs. This report
      presents the highlights and several key presentations, especially the LBCTs, from
      the ACC Scientific Sessions 2015. I hope this review will help cardiologists
      update to the latest information.

PMID- 25959561
TI  - Effects of human pericytes in a murine excision model of wound healing.

PMID- 25959562
TI  - Introducing a new journal: Biological Psychiatry: Cognitive Neuroscience and
      Neuroimaging.

PMID- 25959563
TI  - Possible compensatory mechanisms for glutamatergic disconnection found in the
      auditory cortex in schizophrenia.

PMID- 25959564
TI  - Neuronal misplacement in schizophrenia.

PMID- 25959565
TI  - Network dysconnectivity: a psychosis-triggering mechanism?

PMID- 25959566
TI  - A charge density study of pi-delocalization and intermolecular interactions.
AB  - The compound trans-4,4'-azo-1,2,4-triazole (atrz) is a planar molecule with two
      planar triazole rings bridged by an azo group. The molecule is a good donor
      ligand and has an interesting pi-delocalized character. In addition,
      intermolecular interactions in the crystalline state through pi-pi stacking are
      found between triazole rings with a very short inter-planar distance of 3.17 A.
      The electron density distribution is obtained from both high resolution X-ray
      diffraction data at 100 K and density functional theory (DFT) calculations using
      the omegaB97X-D functional. Bond characterization is performed in terms of the
      charge density distribution and the associated topological properties. The
      Laplacian distribution around each atom reveals the shape of the valence-shell
      charge concentration and demonstrates a sp(2) hybrid orbital shape for each atom
      in the molecule. The pi-delocalization of the planar molecule is further
      illustrated by the Fermi-hole distribution. The weak intermolecular pi-pi
      interactions and hydrogen bonds are further illustrated by the Hirshfeld surface.
      The energies of weak intermolecular pi-pi interactions and hydrogen bonds have
      been calculated using omegaB97X-D/6-311++G(3df,2p) at experimental geometry. 

PMID- 25959567
TI  - Intestinal morphology adjustments caused by dietary restriction improves the
      nutritional status during the aging process of rats.
AB  - During the aging process, the body's systems change structurally and loss of
      function can occur. Ingesting a smaller amount of food has been considered a
      plausible proposal for increased longevity with the quality of life. However, the
      effects of dietary restriction (DR) during aging are still poorly understood,
      especially for organs of the digestive system. This study aimed to describe the
      body weight, oxidative status and possible morphological changes of the
      intestinal wall of rats submitted to DR during the aging process (7 to 18months
      old). Twelve 7-month-old male Wistar rats fed ad libitum since birth were
      assigned to two groups: control group (CG, n=6) fed ad libitum from 7 to 18months
      old; and dietary restriction group (DRG, n=6) fed 50% of the amount of chow
      consumed by the CG from 7 to 18months old. The body weight, feed and water intake
      were monitored throughout the experiment. Blood, periepididymal adipose tissue
      (PAT) and retroperitoneal adipose tissue (RAT), and the small intestine were
      collected at 18months old. The blood was collected to evaluate its components and
      oxidative status. Sections from the duodenum and ileum were stained with HE, PAS
      and AB pH2.5 for morphometric analyses of the intestinal wall components, and to
      count intraepithelial lymphocytes (IELs), goblet cells and cells in mitosis in
      the epithelium. DR rats showed a reduction in weight, naso-anal length, PAT, RAT
      and intestinal length; however, they consumed more water. Blood parameters
      indicate that the DR rats remained well nourished. In addition, they showed lower
      lipid peroxidation. Hypertrophy of the duodenal mucosa and atrophy of the ileal
      mucosa were observed. The number of goblet cells and IELs was reduced, but the
      mitotic index remained unaltered in both duodenum and ileum. In conclusion, 50%
      dietary restriction for rats from 7 to 18months old contributed to improving
      their nutritional parameters but, to achieve this, adjustments were required in
      the structure of the body weight and morphology of the small intestine. 

PMID- 25959568
TI  - Interaction of human serum albumin with short polyelectrolytes: a study by
      calorimetry and computer simulations.
AB  - We present a comprehensive study of the interaction of human serum albumin (HSA)
      with poly(acrylic acid) (PAA; number average degree of polymerization: 25) in
      aqueous solution. The interaction of HSA with PAA is studied in dilute solution
      as a function of the concentration of added salt (20-100 mM) and temperature (25
      37  degrees C). Isothermal titration calorimetry (ITC) is used to analyze the
      interaction and to determine the binding constant and related thermodynamic data.
      It is found that only one PAA chain is bound per HSA molecule. The free energy of
      binding DeltaGb increases with temperature significantly. DeltaGb decreases with
      increasing salt concentration and is dominated by entropic contributions due to
      the release of bound counterions. Coarse-grained Langevin computer simulations
      treating the counterions in an explicit manner are used to study the process of
      binding in detail. These simulations demonstrate that the PAA chains are bound in
      the Sudlow II site of HSA. Moreover, DeltaGb is calculated from the simulations
      and found to be in very good agreement with the measured data. The simulations
      demonstrate clearly that the driving force of binding is the release of
      counterions in full agreement with the ITC-data. 

PMID- 25959569
TI  - Current developments in gene therapy for amyotrophic lateral sclerosis.
AB  - INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a devastating adult
      neurodegenerative disorder characterized by motor neuron degeneration and death
      around 3 years from onset. So far, riluzole is the only treatment available,
      although it only offers a slight increase in survival. The complex etiology of
      ALS, with several genes able to trigger the disease, makes its study difficult.
      AREAS COVERED: RNA-mediated or protein-mediated toxic gain-of-function leading to
      motor neuron degeneration appears to be likely common pathogenic mechanisms in
      ALS. Consequently, gene therapy technologies to reduce toxic RNA and/or proteins
      and to protect motor neurons by modulating gene expression are at the forefront
      of the field. Here, we review the most promising scientific advances, paying
      special attention to the successful treatments tested in animal models as well as
      analyzing relevant gene therapy clinical trials. EXPERT OPINION: Despite broad
      advances in target gene identification in ALS and advances in gene therapy
      technologies, a successful gene therapy for ALS continues to elude researchers.
      Multiple hurdles encompassing technical, biological, economical and clinical
      challenges must be overcome before a therapy for patients becomes available.
      Optimism remains due to positive results obtained in several in vivo studies
      demonstrating significant disease amelioration in animal models of ALS.

PMID- 25959570
TI  - [The Postero-Lateral Approach--An Alternative to Closed Anterior-Posterior Screw
      Fixation of a Dislocated Postero-Lateral Fragment of the Distal Tibia in Complex
      Ankle Fractures].
AB  - BACKGROUND: The dislocated posterolateral fragment of the distal tibia is
      considered as a key fragment for the successful reduction of comminuted ankle
      fractures. The reduction of this fragment can either be achieved indirectly by
      joint reduction using the technique of closed anterior-posterior screw fixation,
      or directly using the open posterolateral approach followed by plate fixation.
      The aim of this study was to compare the outcome after stabilization of the
      dislocated posterolateral tibia fragment using either closed reduction and screw
      fixation, or open reduction and plate fixation via the posterolateral approach in
      complex ankle fractures. PATIENTS/MATERIAL AND METHODS: In a prospective study
      between 01/2010 and 12/2012, all mono-injured patients with closed ankle
      fractures and dislocated posterolateral tibia fragments were assessed 12 months
      after osteosynthesis. Parameters included: size of the posterolateral tibia
      fragment relative to the tibial joint surface (CT scan, in %) as an indicator of
      injury severity, unreduced area of tibial joint surface postoperatively,
      treatment outcome assessed by using the "Ankle Fracture Scoring System" (AFSS),
      as well as epidemiological data and duration of the initial hospital treatment.
      RESULTS: In 11 patients (10 female, 1 male; age 51.6 +/- 2.6 years [mean +/-
      SEM], size of tibia fragment 42.1 +/- 2.5 %) the fragment fixation was performed
      using a posterolateral approach. Impaired postoperative wound healing occurred in
      2 patients of this group. In the comparison group, 12 patients were treated using
      the technique of closed anterior-posterior screw fixation (10 female, 2 male; age
      59.5 +/- 6.7 years, size of tibia fragment 45.9 +/- 1.5 %). One patient of this
      group suffered an incomplete lesion of the superficial peroneal nerve.
      Radiological evaluation of the joint surface using CT scan imaging demonstrated
      significantly less dislocation of the tibial joint surface following the open
      posterolateral approach (0.60 +/- 0.20 mm) compared to the closed anterior
      posterior screw fixation (1.03 +/- 0.08 mm; p < 0.05). Assessment of the
      treatment outcome using the AFSS demonstrated a significantly higher score of
      97.4 +/- 6.4 in the group with a posterolateral approach compared to a score of
      74.4 +/- 12.1 (p < 0.05) in the group with an anterior-posterior screw fixation.
      CONCLUSION: In comparison to the anterior-posterior screw fixation, open
      reduction and fixation of the dislocated, posterolateral key fragment of the
      distal tibia using a posterolateral approach resulted in a more accurate fracture
      reduction and significantly better functional outcome 12 months after surgery. In
      addition, no increased rate of postoperative complications, or extended hospital
      stay was observed but there was less severe post-traumatic joint arthritis. The
      results of this study suggest that in complex ankle factures the open fixation of
      the dislocated posterolateral fragment is recommended as an alternative surgical
      procedure and may be beneficial for both clinical and radiological long-term
      outcomes.

PMID- 25959572
TI  - Physical Continuity and Vertical Alignment of Block Copolymer Domains by
      Kinetically Controlled Electrospray Deposition.
AB  - The fabrication of block copolymer (BCP) thin films is reported with vertically
      aligned cylindrical domains using continuous electrospray deposition onto bare
      wafer surfaces. The out-of-plane orientation of hexagonally packed styrene
      cylinders is achieved in the "fast-wet" deposition regime in which rapid
      evaporation of the solvent in deposited droplets of polymer solution drives the
      vertical alignment of the self-assembled structure. Thermally activated
      crosslinking of the polybutadiene matrix provides kinetic control of the
      morphology, freezing the vertical alignment and preventing relaxation of the
      system to its preferred parallel orientation on the nontreated substrate.
      Physically continuous vertically oriented domains can be achieved over several
      micrometers of film thickness. The ability of electrospray deposition to
      fabricate well-ordered and aligned BCP films on nontreated substrates, the low
      amount of material used relative to spin-coating, and the continuous nature of
      the deposition may open up new opportunities for BCP thin films. 

PMID- 25959573
TI  - CART treatment improves memory and synaptic structure in APP/PS1 mice.
AB  - Major characteristics of Alzheimer's disease (AD) include deposits of beta
      amyloid (Abeta) peptide in the brain, loss of synapses, and cognitive
      dysfunction. Cocaine- and amphetamine-regulated transcript (CART) has recently
      been reported to attenuate Abeta-induced toxicity. In this study, CART
      localization in APP/PS1 mice was characterized and the protective effects of
      exogenous CART treatment were examined. Compared to age-matched wild type mice, 8
      month-old APP/PS1 mice had significantly greater CART immunoreactivity in the
      hippocampus and cortex. A strikingly similar pattern of Abeta plaque-associated
      CART immunoreactivity was observed in the cortex of AD cases. Treatment of
      APP/PS1 mice with exogenous CART ameliorated memory deficits; this effect was
      associated with improvements in synaptic ultrastructure and long-term
      potentiation, but not a reduction of the Abeta plaques. Exogenous CART treatment
      in APP/PS1 mice prevented depolarization of the mitochondrial membrane and
      stimulated mitochondrial complex I and II activities, resulting in an increase in
      ATP levels. CART treatment of APP/PS1 mice also reduced reactive oxygen species
      and 4-hydroxynonenal, and mitigated oxidative DNA damage. In summary, CART
      treatment reduced multiple neuropathological measures and improved memory in
      APP/PS1 mice, and may therefore be a promising and novel therapy for AD. 

PMID- 25959571
TI  - Standardizing terms, definitions and concepts for describing and interpreting
      unwanted immunogenicity of biopharmaceuticals: recommendations of the Innovative
      Medicines Initiative ABIRISK consortium.
AB  - Biopharmaceuticals (BPs) represent a rapidly growing class of approved and
      investigational drug therapies that is contributing significantly to advancing
      treatment in multiple disease areas, including inflammatory and autoimmune
      diseases, genetic deficiencies and cancer. Unfortunately, unwanted immunogenic
      responses to BPs, in particular those affecting clinical safety or efficacy,
      remain among the most common negative effects associated with this important
      class of drugs. To manage and reduce risk of unwanted immunogenicity, diverse
      communities of clinicians, pharmaceutical industry and academic scientists are
      involved in: interpretation and management of clinical and biological outcomes of
      BP immunogenicity, improvement of methods for describing, predicting and
      mitigating immunogenicity risk and elucidation of underlying causes.
      Collaboration and alignment of efforts across these communities is made difficult
      due to lack of agreement on concepts, practices and standardized terms and
      definitions related to immunogenicity. The Innovative Medicines Initiative (IMI;
      www.imi-europe.org), ABIRISK consortium [Anti-Biopharmaceutical (BP) Immunization
      Prediction and Clinical Relevance to Reduce the Risk; www.abirisk.eu] was formed
      by leading clinicians, academic scientists and EFPIA (European Federation of
      Pharmaceutical Industries and Associations) members to elucidate underlying
      causes, improve methods for immunogenicity prediction and mitigation and
      establish common definitions around terms and concepts related to immunogenicity.
      These efforts are expected to facilitate broader collaborations and lead to new
      guidelines for managing immunogenicity. To support alignment, an overview of
      concepts behind the set of key terms and definitions adopted to date by ABIRISK
      is provided herein along with a link to access and download the ABIRISK terms and
      definitions and provide comments (http://www.abirisk.eu/index_t_and_d.asp). 

PMID- 25959575
TI  - Rapid diagnosis of Mycobacterium abscessus hand infection by oligonucleotide
      array in an immunocompetent patient.

PMID- 25959574
TI  - Comparative analysis of adaptive immune response after vaccine trials using live
      attenuated and formalin-killed cells of Edwardsiella tarda in ginbuna crucian
      carp (Carassius auratus langsdorfii).
AB  - Edwardsiella tarda is an intracellular pathogen that causes edwardsiellosis in
      fish. Although vaccine trials with formalin-killed cells (FKC) have been
      reported, the vaccinations failed in protect against E. tarda infection. On the
      other hand, a live attenuated vaccine strategy is effective against
      edwardsiellosis; however, the mechanism underlying its effectiveness in fish is
      unclear. In the present study, we compared the adaptive immune responses in fish
      vaccinated with FKCs and live attenuated vaccines to elucidate the induction of
      adaptive immune responses following vaccination. After challenge with E. tarda,
      live cell (LC)-vaccinated fish showed high survival rates, high IFN-g and T-bet
      gene expression levels, and increased cytotoxic T lymphocytes (CTLs). In
      contrast, all FKC-vaccinated fish died following E. tarda infection. In addition,
      FKC vaccination induced high IL-4/13A and IL-10 expression levels and increased
      antibody titers, whereas Th1-like responses were suppressed. These results
      indicate that LC vaccination contributes to protection against E. tarda infection
      by inducing cell-mediated immunity (CMI). Thus our study findings could
      contribute to the development a vaccine that induces CMI against edwardsiellosis.

PMID- 25959576
TI  - Odd-parity magnetoresistance in pyrochlore iridate thin films with broken time
      reversal symmetry.
AB  - A new class of materials termed topological insulators have been intensively
      investigated due to their unique Dirac surface state carrying dissipationless
      edge spin currents. Recently, it has been theoretically proposed that the three
      dimensional analogue of this type of band structure, the Weyl Semimetal phase, is
      materialized in pyrochlore oxides with strong spin-orbit coupling, accompanied by
      all-in-all-out spin ordering. Here, we report on the fabrication and
      magnetotransport of Eu2Ir2O7 single crystalline thin films. We reveal that one of
      the two degenerate all-in-all-out domain structures, which are connected by time
      reversal operation, can be selectively formed by the polarity of the cooling
      magnetic field. Once formed, the domain is robust against an oppositely polarised
      magnetic field, as evidenced by an unusual odd field dependent term in the
      magnetoresistance and an anomalous term in the Hall resistance. Our findings pave
      the way for exploring the predicted novel quantum transport phenomenon at the
      surfaces/interfaces or magnetic domain walls of pyrochlore iridates. 

PMID- 25959577
TI  - Formal Synthesis of Sarain A: Intramolecular Cycloaddition of an Eight-Membered
      Cyclic Nitrone to Construct the 2-Azabicyclo[3.3.1]nonane Framework.
AB  - An enantioselective route to the tetracyclic skeleton of sarain A has been
      developed. Asymmetric reduction of an ynone introduced a chiral center which was
      transferred to the contiguous tertiary stereogenic centers through an Ireland
      Claisen rearrangement. The 2-azabicyclo[3.3.1]nonane framework was constructed by
      an unprecedented intramolecular cycloaddition of an eight-membered cyclic
      nitrone. Using the steric bias of the bicyclic system, the quaternary carbon atom
      was constructed by a stereoselective aldol reaction. Further ring formations were
      performed by ring-closing metathesis for the 13-membered ring and an
      iodoamidation reaction for the pyrrolidine ring. The present synthesis has
      successfully provided an alternative route to the late-stage intermediate of
      Overman's synthesis. 

PMID- 25959578
TI  - Deciphering intracellular events triggered by mild magnetic hyperthermia in vitro
      and in vivo.
AB  - AIM: To assess the cell response to magnetic nanoparticles under an alternating
      magnetic field by molecular quantification of heat responsive transcripts in two
      model systems. MATERIALS & METHODS: Melanoma cells and Hydra vulgaris treated
      with magnetic nanoparticles were subjected to an alternating magnetic field or to
      macroscopic heating. Effect to these treatments were assessed at animal, cellular
      and molecular levels. RESULTS: By comparing hsp70 expression following both
      treatments, thermotolerance pathways were found in both systems in absence of
      cell ablation or global temperature increment. CONCLUSION: Analysis of hsp70
      transcriptional activation can be used as molecular thermometer to sense cells'
      response to magnetic hyperthermia. Similar responses were found in cells and
      Hydra, suggesting a general mechanism to the delivery of sublethal thermal doses.

PMID- 25959579
TI  - Soil application of Beauveria bassiana GHA against apple sawfly, Hoplocampa
      testudinea (Hymenoptera: Tenthredinidae): Field mortality and fungal persistence.
AB  - Low impact alternatives to synthetic insecticides for the control of apple sawfly
      (Hoplocampa testudinea Klug) are scarce encumbering pest management in organic
      apple orchards. We investigated the soil persistence and field efficacy of the
      entomopathogenic fungus Beauveria bassiana (Balsamo) Vuillemin (BotaniGard)
      against apple sawfly under common organic orchard practices. We also assessed the
      efficacy of B. bassiana GHA and Metarhizium brunneum Petch (indigenous strain)
      against sawfly in the laboratory. Larvae treated with either fungus in the
      laboratory died faster than control larvae and displayed 49.4%-68.4% mycosis. In
      the field, B. bassiana density remained high in the week after application,
      during larval descent to the soil. Fungal density decreased to 25% at 49 d after
      application and to 0.4% after 55 weeks. Molecular markers revealed that the
      majority of fungal isolates recovered comprised the applied B. bassiana strain
      GHA. Larvae pupating in soil cages in the orchard for 49 d displayed 17% mycosis.
      The high efficacy under laboratory conditions was not seen in the field. B.
      bassiana application resulted in densities above the upper natural background
      level during the growing season, but reversion to background levels occurred
      within a year. It remains to be investigated whether this has a detrimental
      effect on nontarget organisms. Additional work is needed to bridge the knowledge
      gap between laboratory and field efficacy in orchards.

PMID- 25959580
TI  - Unexpected lateral-lithiation-induced alkylative ring opening of tetrahydrofurans
      in deep eutectic solvents: synthesis of functionalised primary alcohols.
AB  - o-Tolyl-substituted tetrahydrofurans undergo highly regioselective ring opening
      with the concomitant formation of new C-C bonds as the result of a lateral
      lithiation reaction. This reaction provides a new method for the synthesis of
      functionalised primary alcohols and can be run directly in protic eutectic
      mixtures as benign reaction media at 0  degrees C and under air, competitively
      with protonolysis. 

PMID- 25959581
TI  - Antibodies to Domain 4/5 (Dm4/5) of beta2-Glycoprotein 1 (beta2GP1) in different
      antiphospholipid (aPL) antibody profiles.
AB  - BACKGROUND: Determination of the three recommended tests for the diagnosis of
      antiphospholipid syndrome [Lupus Anticoagulant (LA), anticardiolipin (aCL) and
      anti beta2-Glycoprotein 1 (abeta2GP1) antibodies] allow physicians to allocate
      patients into classification (risk) categories. OBJECTIVES: To measure antibodies
      of IgG isotype directed towards Domain 4/5 (Dm4/5) of beta2GP1. PATIENTS/METHODS:
      In this cross-sectional study we measured IgG abeta2GP1-Dm4/5 in a group of
      individuals positive for IgG abeta2GP1 and classified as triple (LAC+, IgG aCL+,
      IgG abeta2GP1+, n=32), double (LAC-, IgG aCL+, IgG abeta2GP1+, n=23) or single
      positive (LA-, IgG aCL-, IgG abeta2GP1+, n=10). RESULTS: Geometric mean and
      standard deviation of IgG abeta2GP1 values expressed as Chemiluminescent Units
      (CU) in triple, double, single positive groups and in 40 healthy individuals were
      1795+/-783, 321+/-181, 29+/-8 and 5.0+/-1.0, respectively (ANOVA p<0.0001).
      Geometric mean and standard deviation of IgG abeta2GP1-Dm4/5 expressed as Optical
      Density (OD) in triple, double and single positive groups and in 40 healthy
      individuals were 0.16+/-0.13, 0.16+/-0.15 and 0.26+/-0.15, 0.13+/-0,11,
      respectively (ANOVA p<0.002). Individuals in the single positive group, expressed
      significantly higher values with respect to triple (p=0.04) and double (p=0.03)
      positive groups. Approximate OD cut-off value (99 degrees  percentile) calculated
      in 40 normal control subjects is 0.404. Positivity to IgG abeta2GP1-Dm4/5
      according to this cutoff was found in only 5 individuals, 3 in triple positive
      and 2 in single positive groups and was not associated with thromboembolism.
      CONCLUSION: Mean level of IgG abeta2GP1-Dm4/5 is higher in single positive group.
      There is no association between positivity to IgG abeta2GP1-Dm4/5 and
      thromboembolic events.

PMID- 25959582
TI  - Long-term stability of international standards for thromboplastin stored at -20
      degrees C, -70 degrees C, and -150 degrees C.
AB  - BACKGROUND: Long-term stability is an essential requirement for all international
      biological standards. The main stocks of the current international standards for
      thromboplastin, i.e. RBT/05 (rabbit brain thromboplastin) and rTF/09 (recombinant
      human tissue factor), are stored at -20 degrees C. The aim of the present study
      is to assess the long-term stability of the international sensitivity index (ISI)
      for RBT/05 and rTF/09. METHODS: Part of the main stocks of RBT/05 and rTF/09 were
      stored at -70 degrees C and -150 degrees C, up to 38months. At various time
      points samples were taken from the materials stored at -20 degrees C, -70 degrees
      C, and -150 degrees C. The samples were reconstituted and analysed in the
      prothrombin time (PT) test using plasma samples derived from healthy subjects and
      patients treated with vitamin K-antagonists (VKA). The PT's obtained with the
      standards stored at -20 degrees C were compared to the PT's obtained with the
      standards stored at -70 degrees C and at -150 degrees C. The PT's were used to
      calculate relative ISI values by means of orthogonal regression. RESULTS: There
      were no important differences between the ISI values for the materials stored at 
      20 degrees C, -70 degrees C, and -150 degrees C. There was no significant trend
      with storage time. CONCLUSION: The ISI values for the international standards
      RBT/05 and rTF/09 appear to be stable at storage temperatures of -20 degrees C, 
      70 degrees C, and -150 degrees C.

PMID- 25959583
TI  - The early management of DVT in the North West of England: A nation-wide problem?
AB  - BACKGROUND: Despite NICE guidelines, the early management of deep vein thrombosis
      (DVT) in UK hospitals varies widely. We investigated the variation in clinical
      pathways used in NHS hospitals in North West England. METHODS: A detailed
      questionnaire was sent to seventeen University or District General hospitals with
      an Accident and Emergency department. Copies of protocols or patient pathways
      were requested. RESULTS: 15 hospitals responded despite our repeated requests for
      information. Of those, four hospitals did not provide any DVT protocol, guideline
      or service for DVT. In seven (63.6%) hospitals, possible DVT patients were
      assessed in A&E, and four (36.4%) in Acute Medical Admission Units. During the
      day, initial assessment was by a Specialist Nurse (SN)/Advance Nurse Practitioner
      (ANP) in 4 (36.4%) hospitals, by a doctor in 5 out of 11 hospitals (45.5%) and a
      combination of ANP and doctors in 2 out of 11 (18.2%) hospitals. Out of hours
      assessment was conducted by a doctor in all 11 hospitals (100%). Two (18.2%)
      hospitals used the 2003 Wells score, three (27.3%) used the 1997 Wells score and
      six (54.5%) hospitals used 'in house' modified Wells score. The score required to
      trigger further investigation varied between different hospitals. Only four
      (36.4%) hospitals could arrange US imaging within four hours of presentation.
      CONCLUSION: This lack of co-ordinated services for the management of DVT in the
      North West England is likely to reflect national practice. A national programme
      is urgently needed to ensure patients with suspected DVT are managed using
      standardised and consistent protocols.

PMID- 25959584
TI  - A genome scan for candidate genes involved in the adaptation of turbot
      (Scophthalmus maximus).
AB  - Partitioning phenotypic variance in genotypic and environmental variance may
      benefit from the population genomic assignment of genes putatively involved in
      adaptation. We analyzed a total of 256 markers (120 microsatellites and 136
      Single Nucleotide Polymorphisms - SNPs), several of them associated to
      Quantitative Trait Loci (QTL) for growth and resistance to pathologies, with the
      aim to identify potential adaptive variation in turbot Scophthalmus maximus L.
      The study area in the Northeastern Atlantic Ocean, from Iberian Peninsula to the
      Baltic Sea, involves a gradual change in temperature and an abrupt change in
      salinity conditions. We detected 27 candidate loci putatively under selection. At
      least four of the five SNPs identified as outliers are located within genes
      coding for ribosomal proteins or directly related with the production of cellular
      proteins. One of the detected outliers, previously identified as part of a QTL
      for growth, is a microsatellite linked to a gene coding for a growth factor
      receptor. A similar set of outliers was detected when natural populations were
      compared with a sample subjected to strong artificial selection for growth along
      four generations. The observed association between FST outliers and growth
      related QTL supports the hypothesis of changes in growth as an adaptation to
      differences in temperature and salinity conditions. However, further work is
      needed to confirm this hypothesis. 

PMID- 25959585
TI  - An assessment of the barriers to the consumers' uptake of genetically modified
      foods: a neural network analysis.
AB  - BACKGROUND: This paper studies which of the attitudinal, cognitive and socio
      economic factors determine the willingness to purchase genetically modified (GM)
      food, enabling the forecasting of consumers' behaviour in Andalusia, southern
      Spain. This classification has been made by a standard multilayer perceptron
      neural network trained with extreme learning machine. Later, an ordered logistic
      regression was applied to determine whether the neural network can outperform
      this traditional econometric approach. RESULTS: The results show that the highest
      relative contributions lie in the variables related to perceived risks of GM
      food, while the perceived benefits have a lower influence. In addition, an
      innovative attitude towards food presents a strong link, as does the perception
      of food safety. The variables with the least relative contribution are subjective
      knowledge about GM food and the consumers' age. The neural network approach
      outperforms the correct classification percentage from the ordered logistic
      regression. CONCLUSION: The perceived risks must be considered as a critical
      factor. A strategy to improve the GM food acceptance is to develop a transparent
      and balanced information framework that makes the potential risk understandable
      by society, and make them aware of the risk assessments for GM food in the EU.
      For its success, it is essential to improve the trust in EU institutions and
      scientific regulatory authorities.

PMID- 25959586
TI  - Regeneration of beta-Carotene from the Radical Cation by Tyrosine and Tryptophan.
AB  - The phenolic amino acid tyrosine (Tyr) was found more efficient in regenerating
      beta-carotene (beta-Car) from the radical cation (beta-Car(*+)) than tryptophan
      (Trp) in the presence of base for conditions where the reduction potentials for
      Trp and Tyr are comparable. Electron transfer from Tyr in 4:1 chloroform/methanol
      to beta-Car(*+) in the presence of excess base, (CH3)4N(+)OH(-), had a rate close
      to diffusion control and a second-order rate constant in agreement with the
      Marcus theory for electron transfer when compared to plant phenols. A maximum of
      40% beta-Car was regenerated for ten times excess of Tyr as studied by 532 nm
      laser flash photolysis followed by transient absorption spectroscopy in the
      visible and near-infrared regions. The nonregenerated fraction of beta-Car is
      assigned to secondary degradation processes. For Trp, the rate constant for
      regeneration of beta-Car(*+) was 1 order of magnitude smaller compared to Tyr and
      slower than expected from Marcus theory by comparison with plant phenols. 

PMID- 25959587
TI  - Parallel tagged amplicon sequencing of relatively long PCR products using the
      Illumina HiSeq platform and transcriptome assembly.
AB  - In phylogenetics and population genetics, a large number of loci are often needed
      to accurately resolve species relationships. Normally, loci are enriched by PCR
      and sequenced by Sanger sequencing, which is expensive when the number of
      amplicons is large. Next-generation sequencing (NGS) techniques are increasingly
      used for parallel amplicon sequencing, which reduces sequencing costs
      tremendously, but has not reduced preparation costs very much. Moreover, for most
      current NGS methods, amplicons need to be purified and quantified before
      sequencing and their lengths are also restricted (normally <700 bp). Here, we
      describe an approach to sequence pooled amplicons of any length using the
      Illumina platform. Using this method, amplicons are pooled at equal volume rather
      than at equal concentration, thus eliminating the laborious purification and
      quantification steps. We then shear the pooled amplicons, repair the ends, add
      sample identifying linkers and pool multiple samples prior to Illumina library
      preparation. Data are then assembled using the transcriptome assembly program
      trinity, which is optimized to deal with templates of highly varying quantities.
      We demonstrated the utility of our approach by recovering 93.5% of the target
      amplicons (size up to 1650 bp) in full length for a 16 taxa * 101 loci project,
      using ~2.0 GB of Illumina HiSeq paired-end 90-bp data. Overall, we validate a
      rapid, cost-effective and scalable approach to sequence a large number of
      targeted loci from a large number of samples that is particularly suitable for
      both phylogenetics and population genetics studies that require a modest scale of
      data.

PMID- 25959589
TI  - Immunosuppressive minimization with mTOR inhibitors and belatacept.
AB  - Immunosuppressive therapy after kidney transplantation consists of a calcineurin
      inhibitor (CNI)-based therapy in combination with mycophenolic acid and steroids
      in most cases. In spite of low acute rejection rates and excellent graft
      survival, it is associated with major long-term complications, such as
      cardiovascular events, malignancy, and nephrotoxicity, and does not favor
      tolerogenic processes. Mammalian target of rapamycin (mTOR) inhibitors in
      combination with low-dose CNI offer good rejection rates and acceptable allograft
      function; however, de novo mTOR inhitibor-based treatment in combination with
      mycophenolate is not widely used due to higher acute rejection rates. Early
      conversion from a CNI to an mTOR inhibitor is a feasible option in selected
      patients with a slightly higher acute rejection rate, but equal or better GFR.
      Costimulation blockade has been proven to facilitate antirejection prophylaxis
      without CNI-associated side effects. So far, belatacept has been approved in
      combination with mycophenolate and steroids with better graft function, however,
      a slightly higher acute rejection rate. Recently, the combination of an mTOR
      inhibitor and belatacept with lymphocyte-depleting antibody induction and without
      maintenance steroids has been explored in two pilot studies with very low acute
      rejection rates, very good graft function, and an acceptable side effect profile.

PMID- 25959588
TI  - Chip-based analysis of exosomal mRNA mediating drug resistance in glioblastoma.
AB  - Real-time monitoring of drug efficacy in glioblastoma multiforme (GBM) is a major
      clinical problem as serial re-biopsy of primary tumours is often not a clinical
      option. MGMT (O(6)-methylguanine DNA methyltransferase) and APNG (alkylpurine-DNA
      N-glycosylase) are key enzymes capable of repairing temozolomide-induced DNA
      damages and their levels in tissue are inversely related to treatment efficacy.
      Yet, serial clinical analysis remains difficult, and, when done, primarily relies
      on promoter methylation studies of tumour biopsy material at the time of initial
      surgery. Here we present a microfluidic chip to analyse mRNA levels of MGMT and
      APNG in enriched tumour exosomes obtained from blood. We show that exosomal mRNA
      levels of these enzymes correlate well with levels found in parental cells and
      that levels change considerably during treatment of seven patients. We propose
      that if validated on a larger cohort of patients, the method may be used to
      predict drug response in GBM patients. 

PMID- 25959590
TI  - Using abiotic variables to predict importance of sites for species
      representation.
AB  - In systematic conservation planning, species distribution data for all sites in a
      planning area are used to prioritize each site in terms of the site's importance
      toward meeting the goal of species representation. But comprehensive species data
      are not available in most planning areas and would be expensive to acquire. As a
      shortcut, ecologists use surrogates, such as occurrences of birds or another well
      surveyed taxon, or land types defined from remotely sensed data, in the hope that
      sites that represent the surrogates also represent biodiversity. Unfortunately,
      surrogates have not performed reliably. We propose a new type of surrogate,
      predicted importance, that can be developed from species data for a q% subset of
      sites. With species data from this subset of sites, importance can be modeled as
      a function of abiotic variables available at no charge for all terrestrial areas
      on Earth. Predicted importance can then be used as a surrogate to prioritize all
      sites. We tested this surrogate with 8 sets of species data. For each data set,
      we used a q% subset of sites to model importance as a function of abiotic
      variables, used the resulting function to predict importance for all sites, and
      evaluated the number of species in the sites with highest predicted importance.
      Sites with the highest predicted importance represented species efficiently for
      all data sets when q = 25% and for 7 of 8 data sets when q = 20%. Predicted
      importance requires less survey effort than direct selection for species
      representation and meets representation goals well compared with other surrogates
      currently in use. This less expensive surrogate may be useful in those areas of
      the world that need it most, namely tropical regions with the highest
      biodiversity, greatest biodiversity loss, most severe lack of inventory data, and
      poorly developed protected area networks. 

PMID- 25959591
TI  - Effects of atorvastatin on oxidative stress in chronic kidney disease.
AB  - AIM: Statins have pleiotropic effects that include attenuation of oxidative
      stress that may be relevant for chronic kidney disease (CKD) patients. We
      investigated the effect of long-term atorvastatin therapy on oxidative stress
      biomarkers in CKD patients. METHODS: This was a pre-specified secondary analysis
      of data from a randomized, double-blind, placebo-controlled trial (Lipid lowering
      and Onset of Renal Disease, LORD) in CKD patients. Participants received 10
      mg/day atorvastatin (n = 47) or placebo (n = 39) for 3 years. Plasma measures
      (total F2-isoprostanes, malondialdehyde. protein carbonyls, uric acid,
      glutathione peroxidase (GPx) activity and total antioxidant capacity (TAC) ) were
      performed at baseline and at 3 years. Age and sex matched participants (n = 34)
      with normal kidney function were controls. RESULTS: CKD patients had
      significantly (P < 0.05) increased F2-isoprostanes and uric acid and decreased
      GPx activity compared with controls. When comparing the treatment (atorvastatin
      (A) vs placebo (P) ) change from baseline to 3 years, there were no significant
      differences (P > 0.05) in the group difference of the change values: (mean (95%
      CI), F2-isoprostanes = 5.3 (-29.2 to 39.8) pg/mL, protein carbonyls = 0.03 (-0.13
      to 0.19) nmol/mg, GPx activity = -0.10 (-4.73 to 4.52) (U/L), uric acid = 8.8 (
      33.9 to 51.6) MUmol/L or TAC = -0.03 (-0.10 to 0.04) mmol/L. A significant
      difference (P = 0.04) in the change in malondialdehyde between groups, 1.52(0.09
      to 2.96) MUmol/L, was due to a large decrease in the placebo group. CONCLUSION:
      CKD patients had elevated oxidative stress that was not attenuated by
      atorvastatin 10 mg/day for 3 years.

PMID- 25959592
TI  - Direct social perception, mindreading and Bayesian predictive coding.
AB  - Mindreading accounts of social cognition typically claim that we cannot directly
      perceive the mental states of other agents and therefore have to exercise certain
      cognitive capacities in order to infer them. In recent years this view has been
      challenged by proponents of the direct social perception (DSP) thesis, who argue
      that the mental states of other agents can be directly perceived. In this paper
      we show, first, that the main disagreement between proponents of DSP and
      mindreading accounts has to do with the so-called 'sandwich model' of social
      cognition. Although proponents of DSP are critical of this model, we argue that
      they still seem to accept the distinction between perception, cognition and
      action that underlies it. Second, we contrast the sandwich model of social
      cognition with an alternative theoretical framework that is becoming increasingly
      popular in the cognitive neurosciences: Bayesian Predictive Coding (BPC). We show
      that the BPC framework renders a principled distinction between perception,
      cognition and action obsolete, and can accommodate elements of both DSP and
      mindreading accounts. 

PMID- 25959593
TI  - A peptide N-terminal protection strategy for comprehensive glycoproteome analysis
      using hydrazide chemistry based method.
AB  - Enrichment of glycopeptides by hydrazide chemistry (HC) is a popular method for
      glycoproteomics analysis. However, possible side reactions of peptide backbones
      during the glycan oxidation in this method have not been comprehensively studied.
      Here, we developed a proteomics approach to locate such side reactions and found
      several types of the side reactions that could seriously compromise the
      performance of glycoproteomics analysis. Particularly, the HC method failed to
      identify N-terminal Ser/Thr glycopeptides because the oxidation of vicinal amino
      alcohol on these peptides generates aldehyde groups and after they are covalently
      coupled to HC beads, these peptides cannot be released by PNGase F for
      identification. To overcome this drawback, we apply a peptide N-terminal
      protection strategy in which primary amine groups on peptides are chemically
      blocked via dimethyl labeling, thus the vicinal amino alcohols on peptide N
      termini are eliminated. Our results showed that this strategy successfully
      prevented the oxidation of peptide N-termini and significantly improved the
      coverage of glycoproteome. 

PMID- 25959594
TI  - Neurobiological indicators of disinhibition in posttraumatic stress disorder.
AB  - Deficits in impulse control are increasingly recognized in association with
      posttraumatic stress disorder (PTSD). To our further understanding of the
      neurobiology of PTSD-related disinhibition, we examined alterations in brain
      morphology and network connectivity associated with response inhibition failures
      and PTSD severity. The sample consisted of 189 trauma-exposed Operation Enduring
      Freedom/Operation Iraqi Freedom veterans (89% male, ages 19-62) presenting with a
      range of current PTSD severity. Disinhibition was measured using commission
      errors on a Go/No-Go (GNG) task with emotional stimuli, and PTSD was assessed
      using a measure of current symptom severity. Whole-brain vertex-wise analyses of
      cortical thickness revealed two clusters associated with PTSD-related
      disinhibition (Monte Carlo cluster corrected P < 0.05). The first cluster
      included portions of right inferior and middle frontal gyri and frontal pole. The
      second cluster spanned portions of left medial orbital frontal, rostral anterior
      cingulate, and superior frontal gyrus. In both clusters, commission errors were
      associated with reduced cortical thickness at higher (but not lower) levels of
      PTSD symptoms. Resting-state functional magnetic resonance imaging analyses
      revealed alterations in the functional connectivity of the right frontal cluster.
      Together, study findings suggest that reductions in cortical thickness in regions
      involved in flexible decision-making, emotion regulation, and response inhibition
      contribute to impulse control deficits in PTSD. Furthermore, aberrant coupling
      between frontal regions and networks involved in selective attention,
      memory/learning, and response preparation suggest disruptions in functional
      connectivity may also play a role.

PMID- 25959595
TI  - Impact of Instructors' Caring on Students' Perceptions of Their Own Caring
      Behaviors.
AB  - PURPOSE: The aim of this study was to identify the correlation between
      instructors' and students' caring behaviors and to explore the impact of
      instructors' caring on students' perceptions of their own caring behaviors.
      DESIGN: A descriptive, nonexperimental design was used in this study. METHODS: A
      total of 586 student nurses from four countries (Greece, the Philippines, India,
      and Nigeria) were recruited to participate in this study during the months of
      September 2013 to January 2014. Data collection was based on interviews using two
      standardized questionnaires: the Nursing Students' Perception of Instructor
      Caring (NSPIC) and the Caring Behavior Inventory (CBI). Inferential statistics
      such as the Pearson r correlation and regression analysis were used to determine
      correlations between relevant variables. FINDINGS: Student nurses perceived
      "instills confidence through caring" (mean = 4.275, SD = 0.755) as the most
      frequently demonstrated subscale, while "control vs. flexibility" (mean = 3.469,
      SD = 0.701) was the least demonstrated subscale. The highest self-reported
      subscale in the CBI was "assurance" (mean = 4.796, SD = 0.949), while
      "connectedness" (mean = 4.541, SD = 0.985) was the lowest self-rated subscale.
      The NSPIC correlated significantly with the CBI (r = .587, p < .001). Four of the
      five subscales in the NSPIC correlated significantly with the CBI when considered
      individually; the exception was the "Supportive learning climate" subscale (r =
      .009, p < .40). Among the NSPIC subscales, "instills confidence through caring"
      explained 32% in the CBI and "appreciation of life's meaning" explained 3% in the
      CBI. CONCLUSIONS: Instructors' caring behaviors influenced nursing students'
      caring behaviors positively. Through positive faculty modeling and role modeling,
      nursing students can be professionally trained to develop the competence of
      caring. CLINICAL RELEVANCE: The knowledge generated from this study provides
      direction in developing useful and effective caring strategies and curricular
      programs for nursing students. Understanding this concept in a cross-cultural
      context is necessary in order to develop an international perspective about
      caring, which is necessary in developing and formulating effective teaching and
      clinical strategies.

PMID- 25959596
TI  - Active graphene-silicon hybrid diode for terahertz waves.
AB  - Controlling the propagation properties of the terahertz waves in graphene holds
      great promise in enabling novel technologies for the convergence of electronics
      and photonics. A diode is a fundamental electronic device that allows the passage
      of current in just one direction based on the polarity of the applied voltage.
      With simultaneous optical and electrical excitations, we experimentally
      demonstrate an active diode for the terahertz waves consisting of a graphene
      silicon hybrid film. The diode transmits terahertz waves when biased with a
      positive voltage while attenuates the wave under a low negative voltage, which
      can be seen as an analogue of an electronic semiconductor diode. Here, we obtain
      a large transmission modulation of 83% in the graphene-silicon hybrid film, which
      exhibits tremendous potential for applications in designing broadband terahertz
      modulators and switchable terahertz plasmonic and metamaterial devices. 

PMID- 25959597
TI  - Sexual size dimorphism in anadromous brown trout Salmo trutta.
AB  - Anadromous trout Salmo trutta exhibits sexual size dimorphism (SSD ); females
      were larger than males in populations where male mean total length (LT ) at
      maturity was below 49 cm and females were smaller than males when mean male LT
      was above 49 cm, the slope of the regression of female on male LT was 0.59. In
      streams with mean annual discharge below 41 m(3) s(-1) , flow added significantly
      to a model with SSD as the dependent variable and male mean LT at maturity as the
      first predictor variable. There was a slight increase in SSD with increasing
      latitude, which may result from an increase in male size with increasing
      latitude. 

PMID- 25959598
TI  - Analysis of ATP-citrate lyase and malic enzyme mutants of Yarrowia lipolytica
      points out the importance of mannitol metabolism in fatty acid synthesis.
AB  - The role of the two key enzymes of fatty acid (FA) synthesis, ATP-citrate lyase
      (Acl) and malic enzyme (Mae), was analyzed in the oleaginous yeast Yarrowia
      lipolytica. In most oleaginous yeasts, Acl and Mae are proposed to provide,
      respectively, acetyl-CoA and NADPH for FA synthesis. Acl was mainly studied at
      the biochemical level but no strain depleted for this enzyme was analyzed in
      oleaginous microorganisms. On the other hand the role of Mae in FA synthesis in
      Y. lipolytica remains unclear since it was proposed to be a mitochondrial NAD(H)
      dependent enzyme and not a cytosolic NADP(H)-dependent enzyme. In this study, we
      analyzed for the first time strains inactivated for corresponding genes.
      Inactivation of ACL1 decreases FA synthesis by 60 to 80%, confirming its
      essential role in FA synthesis in Y. lipolytica. Conversely, inactivation of MAE1
      has no effects on FA synthesis, except in a FA overaccumulating strain where it
      improves FA synthesis by 35%. This result definitively excludes Mae as a major
      key enzyme for FA synthesis in Y. lipolytica. During the analysis of both
      mutants, we observed a negative correlation between FA and mannitol level. As
      mannitol and FA pathways may compete for carbon storage, we inactivated YlSDR,
      encoding a mannitol dehydrogenase converting fructose and NADPH into mannitol and
      NADP+. The FA content of the resulting mutant was improved by 60% during growth
      on fructose, demonstrating that mannitol metabolism may modulate FA synthesis in
      Y. lipolytica.

PMID- 25959599
TI  - Acquired Immunoglobulin G deficiency in stroke patients and experimental brain
      ischemia.
AB  - BACKGROUND AND PURPOSE: Acute brain injuries induce a systemic immune depression
      syndrome (SIDS) that predisposes patients to bacterial infections. While cellular
      compartments of this syndrome have been well characterized, the contribution of
      humoral immune mechanisms and particularly immunoglobulins to SIDS has not been
      investigated so far. METHODS: We determined serum immunoglobulin levels and
      infectious complications at several time points in 159 ischemic and hemorrhagic
      stroke patients. Additionally, findings were verified in a transient middle
      cerebral artery occlusion model. A novel immunoassay was established to analyze
      the IgG excretion ratio in mice. RESULTS: We identified a transient IgG reduction
      in patients suffering from substantial ischemic or hemorrhagic brain injuries.
      The IgG-reduction was associated with subsequent bacterial infections. Similarly,
      transient hypogammaglobulinemia was detected in a murine stroke model. We then
      used this animal model to further distinguish the mechanism of the IgG reduction
      by an IgG transfer paradigm. Excretional loss rather than deficient production of
      IgG was demonstrated to underlay hypogammaglobulinemia. CONCLUSIONS: This is the
      first report of transient hypogammaglobulinemia after ischemic and hemorrhagic
      stroke suggesting involvement in infectious complications. These findings pave
      the road for further studies investigating post-stroke hypogammaglobulinemia as a
      druggable target for stroke-induced complications.

PMID- 25959600
TI  - Quitting smoking: The importance of non-smoker identity in predicting smoking
      behaviour and responses to a smoking ban.
AB  - OBJECTIVE: We examined how 'smoker' and 'non-smoker' self- and group-identities
      and socio-economic status (SES) may predict smoking behaviour and responses to
      antismoking measures (i.e., the Dutch smoking ban in hospitality venues). We
      validated a measure of responses to the smoking ban. DESIGN: Longitudinal online
      survey study with one-year follow-up (N = 623 at T1 in 2011; N = 188 at T2 in
      2012) among daily smokers. MAIN OUTCOME MEASURES: Intention to quit, quit
      attempts and 'rejecting', 'victimizing', 'socially conscious smoking' and 'active
      quitting' responses to the smoking ban. RESULTS: Non-smoker identities are more
      important than smoker identities in predicting intention to quit, quit attempts
      and responses to the smoking ban, even when controlling for other important
      predictors such as nicotine dependence. Smokers with stronger non-smoker
      identities had stronger intentions to quit, were more likely to attempt to quit
      between measurements, and showed less negative and more positive responses to the
      smoking ban. The association between non-smoker self-identity and intention to
      quit was stronger among smokers with lower than higher SES. CONCLUSION:
      Antismoking measures might be more effective if they would focus also on the
      identity of smokers, and help smokers to increase identification with non-smoking
      and non-smokers.

PMID- 25959601
TI  - The Prognostic Utility of Echo-Estimated Left Ventricular End-Diastolic Pressure
      Volume Relationship in Stable Coronary Artery Disease: The Heart and Soul Study.
AB  - BACKGROUND: While changes in the left ventricular end-diastolic pressure-volume
      relationship (LV-EDPVR) can be estimated using echocardiography, their prognostic
      utility in stable coronary artery disease (CAD) is unknown. METHODS: Using echo
      estimated LV end-diastolic volume index and diastolic function category, the
      relative position of the LV-EDPVR was defined in 901 participants with stable CAD
      as: (1) left-shifted, (2) right-shifted, or (3) intermediate. We then evaluated
      the association of LV-EDPVR position relative to the intermediate category with
      time to hospitalization for heart failure (HF) or cardiovascular (CV) death using
      Cox proportional hazards models. RESULTS: During 7.0 +/- 3.1 years of follow-up,
      there were 207 admissions for HF or CV deaths. Both leftward and rightward shifts
      of LV-EDPVR were associated with a significantly higher risk of HF or CV death
      (HR 1.73, 95% CI 1.15-2.62 and HR 6.75, 95% CI 4.02-11.31, respectively). In
      multivariable-adjusted models, these associations were attenuated but remained
      significant (HR 1.66, 95% CI 1.08-2.55 for left-shifted and HR 4.19, 95% CI 2.32
      7.55 for right-shifted). The association of LV-EDPVR with HF or CV death was no
      longer significant after inclusion of N-terminal pro-brain natriuretic peptide
      level as a covariate. CONCLUSIONS: In stable CAD, echo-estimated leftward and
      rightward shifts in the LV-EDPVR are associated with HF and CV death. The loss of
      these associations after adjustment for N-terminal pro-brain natriuretic peptide
      level suggests that echo-estimated LV-EDPVR captures changes in LV filling
      pressure at any given LV end-diastolic volume.

PMID- 25959602
TI  - Ustekinumab treatment in patients with psoriasis undergoing hemodialysis.
AB  - Patients with psoriasis undergoing hemodialysis have additional difficulties in
      treatment compared with general patients. Conventional treatments such as
      cyclosporin, retinoids and methotrexate are not widely administrated due to the
      chances of an increase in adverse effects and the possibility of risk to patient
      survival. Recently, biologic treatments have been recognized as having sufficient
      efficacy for severe psoriasis with low incidence of organ toxicities. For this
      reason, biologic treatments may be more preferable for patients on hemodialysis;
      however, there is not sufficient evidence. We have treated three patients with
      psoriasis with ustekinumab for 1 year, who had been undergoing hemodialysis. They
      were previously treated with conventional treatments before ustekinumab
      treatments; however, they did not respond to these treatments sufficiently.
      Following treatment with ustekinumab, rapid and maintained improvement in
      psoriasis was observed. Over the course of treatments, two of the three patients
      encountered no adverse events during their first year of treatment. The other
      patient discontinued ustekinumab due to elevated levels of C-reactive protein.
      These findings suggest that ustekinumab may be an appropriate treatment for
      patients undergoing hemodialysis who are suffering from psoriasis. However, the
      risk of developing infection remains higher than in general patients. 

PMID- 25959603
TI  - Pretreatment and process predictors of nonresponse at different stages of
      inpatient psychotherapy.
AB  - OBJECTIVE: Up to 50% of psychotherapeutic treatments end without significant
      improvements. While there is first evidence about predictors of nonresponse in
      outpatient psychotherapy, there are currently no studies investigating predictors
      of nonresponse in inpatient settings. Based upon a previous systematic literature
      review, we analyzed the predictive value of initial patient characteristics on
      nonresponse in symptom distress. METHODS: Treatment episodes from 546 patients,
      treated for at least 4 weeks, were assessed under naturalistic conditions.
      Nonresponse status (i.e., lack of a reliable improvement in symptom distress) was
      investigated at four different time points: at week 4, at discharge, and at a two
      follow-ups (3 and 12 months after discharge). Hierarchical binary logistic
      regression models were used to predict nonresponse. Sociodemographic data,
      clinical variables, and the previous response status were entered subsequently in
      the model. RESULTS: A moderate or functional level of initial symptom distress, a
      comorbid personality disorder, and previous nonresponse were the most consistent
      predictors of nonresponse. CONCLUSIONS: The results point to the importance of
      early outcome assessment and suggest the implementation of more symptom-specific
      treatments.

PMID- 25959604
TI  - Application of the Audio Recorded Cognitive Screen and its relation to
      functioning in schizophrenia.
AB  - OBJECTIVE: This study investigated the ability of the Audio Recorded Cognitive
      Screen (ARCS) to detect cognitive deficit in individuals with schizophrenia,
      relative to the Mini Mental State Examination (MMSE) and the Repeatable Battery
      for the Assessment of Neuropsychological Status (RBANS), and explored the
      associations between the ARCS and functional outcomes. We hypothesised that the
      ARCS would be able to better discriminate between individuals with schizophrenia
      and healthy controls than the MMSE, and that ARCS performance would be correlated
      with measures of social and vocational functioning. METHODS: The participants
      were 19 community-dwelling individuals with schizophrenia or schizoaffective
      disorder and 19 healthy controls recruited from the Australian Schizophrenia
      Research Bank (ASRB). Participants completed the ARCS, MMSE, and self-report
      measures of social and vocational functioning. Clinical and diagnostic data
      stored by the ASRB were also utilised. RESULTS: The schizophrenia group performed
      worse than the control group on the ARCS, with memory, t(36)=2.49, p=0.02, 95% CI
      [-1.84, -18.79] and fluency, t(36)=2.40, p=0.02, 95% CI [-1.87, -22.24] domains
      being the main discriminating measures. The RBANS also discriminated between the
      two groups, and ARCS and RBANS total scores were moderately to strongly
      correlated. There was no difference between the two groups on the MMSE after
      controlling for demographic variables. ARCS performance was associated with
      employment status [chi2(1)=7.16, p=0.007]. CONCLUSION: The ARCS may be sensitive
      to the cognitive deficits in outpatients with schizophrenia and an indicator of
      functional outcomes in this population.

PMID- 25959605
TI  - Forebrain circuits underlying the social modulation of vocal communication
      signals.
AB  - Across vertebrate species, signalers alter the structure of their communication
      signals based on the social context. For example, male Bengalese finches produce
      faster and more stereotyped songs when directing song to females (female-directed
      [FD] song) than when singing in isolation (undirected [UD] song), and such
      changes have been found to increase the attractiveness of a male's song. Despite
      the importance of such social influences, little is known about the mechanisms
      underlying the social modulation of communication signals. To this end, we
      analyzed differences in immediate early gene (EGR-1) expression when Bengalese
      finches produced FD or UD song. Relative to silent birds, EGR-1 expression was
      elevated in birds producing either FD or UD song throughout vocal control
      circuitry, including the interface nucleus of the nidopallium (NIf), HVC, the
      robust nucleus of the arcopallium (RA), Area X, and the lateral magnocellular
      nucleus of the anterior nidopallium (LMAN). Moreover, EGR-1 expression was higher
      in HVC, RA, Area X, and LMAN in males producing UD song than in males producing
      FD song, indicating that social context modulated EGR-1 expression in these
      areas. However, EGR-1 expression was not significantly different between males
      producing FD or UD song in NIf, the primary vocal motor input into HVC,
      suggesting that context-dependent changes could arise de novo in HVC. The pattern
      of context-dependent differences in EGR-1 expression in the Bengalese finch was
      highly similar to that in the zebra finch and suggests that social context
      affects song structure by modulating activity throughout vocal control nuclei.

PMID- 25959606
TI  - Depletion of Kupffer cells attenuates systemic insulin resistance, inflammation
      and improves liver autophagy in high-fat diet fed mice.
AB  - The objective of this study was to reveal the exact role of Kupffer cells in the
      diet-induced insulin resistance, inflammation and liver autophagy. C57BL/6j male
      mice were fed with either chow diet or high-fat diet (HFD) for 12 weeks.
      Meanwhile, HFD feeding mice received an intraperitoneal injection of either 0.2%
      GdCl3 solution (20mg/kg) twice a week to deplete Kupffer cells or natural saline
      (5mL/kg) as control. The mRNA expressions of Kupffer cells markers (CD68 and
      F4/80), insulin sensitivity, TNF-alpha concentration and NF-kappaB activation and
      parameters of autophagy were assessed. Results demonstrated that CD68 and F4/80
      mRNA expressions in the liver were up-regulated in HFD fed animals, while
      significantly reduced after GdCl3 administration. HFD feeding led to insulin
      resistance and TNF-alpha level and activation of NF-kappaB in insulin-sensitive
      tissues (liver, adipose tissue and skeletal muscle) were significantly elevated.
      Interestingly, alterations above were reversed by varying degrees but
      significantly after Kupffer cells depletion. Furthermore, western blot showed
      hepatic LC3-II as well as phosphorylation of AMPK in liver and skeletal muscle
      were significantly lower in mice fed HFD, and these changes dramatically
      ameliorated by GdCl3 treating. In conclusion, selective depletion of Kupffer
      cells significantly attenuated diet-induced insulin resistance, inflammation and
      promoted liver autophagy. Strategies targeting Kupffer cells function or
      autophagic processes could be a promising approach to counteract diet induced
      obesity and related metabolic disorders. 

PMID- 25959607
TI  - Sites of disruption within E1 and E2 genes of HPV16 and association with cervical
      dysplasia.
AB  - Integration of HPV16 DNA into the host chromosome usually disrupts the E1 and/or
      E2 genes. The present study investigated the disruption of E1, E2 genes in a
      total of eighty four HPV16-positive precancerous and cervical cancer specimens
      derived from Greek women (seventeen paraffin-embedded cervical biopsies and sixty
      seven Thin Prep samples). Complete E2 and E1 genes were amplified using three and
      nine overlapping primer sets respectively, in order to define the sites of
      disruption. Extensive mapping analysis revealed that disruption/deletion events
      within E2 gene occurred in high grade and cervical cancer samples (x(2) test, P <
      0.01), while no evidence of E2 gene disruption was documented among low grade
      cervical intraepithelial neoplasias. In addition, disruptions within the E1 gene
      occur both in high and low grade cervical intraepithelial neoplasia. This leads
      to the assumption that in low grade cervical intraepithelial neoplasias only E1
      gene disruption was involved (Fisher's exact test, P < 0.05), while in high grade
      malignancies and cervical cancer cases deletions in both E1 and E2 genes
      occurred. Furthermore, the most prevalent site of disruption of E1 gene was
      located between nucleotides 1059 and 1323, while the most prevalent deleted
      region of the E2 gene was located between nucleotides 3172 and 3649 (E2 hinge
      region). Therefore, it is proposed that each population has its own profile of
      frequencies and sites of disruptions and extensive mapping analysis of E1 and E2
      genes is mandatory in order to determine suitable markers for HPV16 DNA
      integration analysis in distinct populations.

PMID- 25959609
TI  - Electronic clinical records in primary care for estimating disease burden and
      management. An example of COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is a significant health problem in
      developed countries. We aimed to estimate the prevalence of COPD in a single
      Spanish healthcare area. We also aimed to assess if there are any differences in
      prevalence and spirometry use among primary care services by utilizing already
      registered information. We designed a cross-sectional study to determine the
      prevalence of COPD and the performance of spirometries in each primary care
      service. A total of 8,444 patients were diagnosed with COPD, with a prevalence of
      2.6% for individuals older than 39 years. The prevalence increased with age and
      was much higher in men. Significant heterogeneity was found in the prevalence of
      COPD and spirometry use among primary care services. COPD was underdiagnosed and
      there was wide variability in spirometry use in our area. Greater efforts are
      needed to diagnose COPD in order to improve its clinical outcomes and to refine
      registries so that they can be used as reliable sources of information. 

PMID- 25959608
TI  - TNF signals are dispensable for the generation of CD23+ CD21/35-high CD1d-high B
      cells in inflamed lymph nodes.
AB  - Tumor necrosis factor (TNF) is a key cytokine in rheumatoid arthritis (RA)
      pathogenesis, as underscored by the clinical effectiveness of TNF antagonists.
      While several of TNF's key targets in RA are well understood, its many
      pleiotropic effects remain to be elucidated. TNF-transgenic mice develop
      inflammatory-erosive arthritis associated with disruption of draining lymph node
      histology and function, and accumulation of B cells with unique phenotypic and
      functional features consistent with contribution to pathogenesis (B cells in
      inflamed nodes, Bin). Bin cell induction depends on the inflamed
      microenvironment, but the specific signals are unknown. Using anti-TNF treatment
      and TNF-receptor-deficient mice, here we show that Bin cells are induced and
      maintained independently of B cell-intrinsic TNF signals. 

PMID- 25959610
TI  - The role as moderator and mediator in parent education groups--a leadership and
      teaching approach model from a parent perspective.
AB  - AIMS AND OBJECTIVES: To investigate the didactic and social leadership in parent
      education groups based on a parent perspective, and to conceptualise parent
      experiences of the leader roles in these groups. BACKGROUND: Leadership in parent
      education groups has been associated with a lack of confidence in one's ability
      to function in that role. Research on how it can be delivered to produce a
      favourable outcome is scarce. It can be difficult to abandon the role of expert
      and let participants set their own learning agenda. To facilitate these processes
      requires leadership skills, knowledge of group dynamics as well as pedagogical
      skills. DESIGN: Qualitative interview study. METHODS: Semi-structured interviews
      with parents (25 participants, 21 interviews). Transcripts were analysed using,
      first, thematic analysis, then comparative analysis. RESULTS: The study resulted
      in a four-field model, The Leadership - Teaching Approach model. It consists of
      the dimensions 'Teaching approaches' ('Knowledge is imparted' and 'Knowledge is
      jointly constructed'), and 'Leadership approaches' ('Instrumental approach' and
      'Investigative approach'). CONCLUSIONS: Using an investigative approach is
      necessary to get a well-functioning group that can help the expectant and new
      parents in the transition to parenthood. Supervision can help develop an
      awareness of one's professional role as a nurse and leader of a parent education
      group. RELEVANCE TO CLINICAL PRACTICE: The actions and choices of nurses as
      leaders of parent groups have an impact on how the participants perceive and take
      in the content and purpose of the group, and whether they perceive it as
      meaningful. Getting support in reflecting about one's role as a leader in this
      context can help create a learning environment in which the participants can
      become engaged in the activities and be strengthened by the experience.

PMID- 25959611
TI  - NOW vs LATER brain circuits: implications for obesity and addiction.
AB  - Balancing behaviors that provide a reward NOW versus behaviors that provide an
      advantage LATER is critical for survival. We propose a model in which dopamine
      (DA) can favor NOW processes through phasic signaling in reward circuits or LATER
      processes through tonic signaling in control circuits. At the same time, through
      its modulation of the orbitofrontal cortex, which processes salience attribution,
      DA also enables shifting from NOW to LATER, while its modulation of the insula,
      which processes interoceptive information, influences the probability of
      selecting NOW vs LATER actions on the basis of an individual's physiological
      state. Disruptions along these circuits contribute to diverse pathologies,
      including obesity and addiction. 

PMID- 25959612
TI  - Symptom management tasks and behaviors related to chemotherapy in Taiwanese
      outpatients with breast cancer.
AB  - PURPOSE: There are many challenges that patients face when dealing with the side
      effects of chemotherapy. The purpose of this study was to describe the key tasks
      and behaviors that contribute to symptom management and the difficulties relating
      to self-care in the context of chemotherapy in Taiwanese outpatients with breast
      cancer. METHOD: This qualitative study included a purposive sample of 17 women
      with breast cancer, aged 30-64 years, and who had undergone chemotherapy. Data
      were collected via face-to-face semi-structured tape-recorded interviews.
      Qualitative content analysis was performed for the identified themes. RESULTS:
      Four main categories of tasks were identified that reflected the patient's
      experience with the behaviors required for chemotherapy symptom management. These
      task domains included communicating chemotherapy-related concerns, managing
      chemotherapy-related symptoms, managing emotional and interpersonal disturbances,
      and acquiring relevant resources. In particular, the results indicated many
      challenges with behaviors related to self-management under these tasks.
      CONCLUSIONS: Systematic information regarding symptoms relating to chemotherapy
      and self-management strategies should be put into practice at the beginning of
      chemotherapy and following assessment, in addition to the individual support of
      patients during their treatment.

PMID- 25959613
TI  - Bariatric surgery: beta cells in type 2 diabetes remission.
AB  - Bariatric surgery is a new emerging treatment that demonstrates a favourable
      effect on type 2 diabetes, although its underlying mechanisms still remain
      unknown. After receiving bariatric surgery, beta cells undergo the process of
      rebirth, which involves apoptosis evasion, regeneration and improved beta-cell
      function. Therefore, further studies are necessary to elucidate how bariatric
      surgery can resolve type 2 diabetes. Here, our review focuses mainly on beta
      cells, the insulin-generating cells, whose biological features change
      dramatically after bariatric surgery. Copyright (c) 2015 John Wiley & Sons, Ltd. 

PMID- 25959614
TI  - Sewage sludge drying process integration with a waste-to-energy power plant.
AB  - Dewatered sewage sludge from Waste Water Treatment Plants (WWTPs) is encountering
      increasing problems associated with its disposal. Several solutions have been
      proposed in the last years regarding energy and materials recovery from sewage
      sludge. Current technological solutions have relevant limits as dewatered sewage
      sludge is characterized by a high water content (70-75% by weight), even if
      mechanically treated. A Refuse Derived Fuel (RDF) with good thermal
      characteristics in terms of Lower Heating Value (LHV) can be obtained if
      dewatered sludge is further processed, for example by a thermal drying stage.
      Sewage sludge thermal drying is not sustainable if the power is fed by primary
      energy sources, but can be appealing if waste heat, recovered from other
      processes, is used. A suitable integration can be realized between a WWTP and a
      waste-to-energy (WTE) power plant through the recovery of WTE waste heat as
      energy source for sewage sludge drying. In this paper, the properties of sewage
      sludge from three different WWTPs are studied. On the basis of the results
      obtained, a facility for the integration of sewage sludge drying within a WTE
      power plant is developed. Furthermore, energy and mass balances are set up in
      order to evaluate the benefits brought by the described integration. 

PMID- 25959615
TI  - Target-based biomarker selection - Mineralocorticoid receptor-related biomarkers
      and treatment outcome in major depression.
AB  - Aldosterone and mineralocorticoid receptor (MR)-function have been related to
      depression. We examined central and peripheral parameters of MR-function in order
      to characterize their relationship to clinical treatment outcome after six weeks
      in patients with acute depression. 30 patients with a diagnosis of major
      depression were examined 3 times over a 6 week period. Aldosterone and cortisol
      salvia samples were taken at 7.00 a.m. before patients got out of bed. Easy to
      use e-devices were used to measure markers of central MR function, i.e. slow wave
      sleep (SWS) and heart-rate variability (HRV). Salt-taste intensity (STI) and salt
      pleasantness (SP) of a 0.9% salt solution were determined by a newly developed
      scale. In addition, systolic blood pressure (SBP) and plasma electrolytes were
      determined as markers for peripheral MR activity. The relationship between the
      levels of these biomarkers at baseline and the change in clinical outcome
      parameters (Hamilton depression rating scale (HDRS)-21, anxiety, QIDS and BDI)
      after 6 weeks of treatment was investigated. A higher aldosterone/cortisol ratio
      (Aldo/Cort) (n = 17 due to missing values; p < 0.05) and lower SBP (n = 24; p <
      0.05) at baseline predicted poor outcome, as measured with the HDRS, independent
      of gender. Only in male patients higher STI, lower SP, lower SWS (all n = 13) and
      higher HRV (n = 11) at baseline predicted good outcome p < 0.05). Likewise, in
      male patients low baseline sodium appears to be predictive for a poor outcome (n
      = 12; p = 0.05; based on HDRS-6). In conclusion, correlates of higher central MR
      activation are associated with poorer clinical improvement, particularly in men.
      This contrasts with the finding of a peripheral MR-desensitization in more
      refractory patients. As one potential mechanism to consider, sodium loss on the
      basis of dysfunctional peripheral MR function and additional environmental
      factors may trigger increased aldosterone secretion and consequently worse
      outcome. These markers deserve further study as potential biological correlates
      for therapy refractory depression.

PMID- 25959616
TI  - Effects of mood stabilizers on oxidative stress-induced cell death signaling
      pathways in the brains of rats subjected to the ouabain-induced animal model of
      mania: Mood stabilizers exert protective effects against ouabain-induced
      activation of the cell death pathway.
AB  - The present study aimed to investigate the effects of mood stabilizers,
      specifically lithium (Li) and valproate (VPA), on mitochondrial superoxide, lipid
      peroxidation, and proteins involved in cell death signaling pathways in the
      brains of rats subjected to the ouabain-induced animal model of mania. Wistar
      rats received Li, VPA, or saline twice a day for 13 days. On the 7th day of
      treatment, the animals received a single intracerebroventricular injection of
      ouabain or aCSF. After the ICV injection, the treatment with mood stabilizers
      continued for 6 additional days. The locomotor activity of rats was measured
      using the open-field test. In addition, we analyzed oxidative stress parameters,
      specifically levels of phosphorylated p53 (pp53), BAX and Bcl-2 in the brain of
      rats by immunoblot. Li and VPA reversed ouabain-related hyperactivity. Ouabain
      decreased Bcl-2 levels and increased the oxidative stress parameters BAX and pp53
      in the brains of rats. Li and VPA improved these ouabain-induced cellular
      dysfunctions; however, the effects of the mood stabilizers were dependent on the
      protein and brain region analyzed. These findings suggest that the Na(+)/K(+)
      ATPase can be an important link between oxidative damage and the consequent
      reduction of neuronal and glial density, which are both observed in BD, and that
      Li and VPA exert protective effects against ouabain-induced activation of the
      apoptosis pathway. 

PMID- 25959617
TI  - Gambling behaviors and attitudes in adolescent high-school students:
      Relationships with problem-gambling severity and smoking status.
AB  - BACKGROUND AND AIMS: Smoking is associated with more severe/extensive gambling in
      adults. The purpose of this study was to examine relationships between smoking
      and gambling in adolescents. METHODS: Analyses utilized survey data from 1591
      Connecticut high-school students. Adolescents were classified by gambling (Low
      Risk Gambling [LRG], At Risk/Problem Gambling [ARPG]) and smoking (current
      smoker, non-smoker). The main effects of smoking and the smoking-by-gambling
      interactions were examined for gambling behaviors (e.g., type, location), and
      gambling attitudes. Data were analyzed using chi-square and logistic regression;
      the latter controlled for gender, race/ethnicity, grade, and family structure.
      RESULTS: For APRG adolescents, smoking was associated with greater online,
      school, and casino gambling; gambling due to anxiety and pressure; greater time
      spent gambling; early gambling onset; perceived parental approval of gambling;
      and decreased importance of measures to prevent teen gambling. For LRG
      adolescents, smoking was associated with non-strategic gambling (e.g., lottery
      gambling); school gambling; gambling in response to anxiety; gambling for
      financial reasons; greater time spent gambling; and decreased importance of
      measures to prevent teen gambling. Stronger relationships were found between
      smoking and casino gambling, gambling due to pressure, earlier onset of gambling,
      and parental perceptions of gambling for ARPG versus LRG adolescents. DISCUSSION:
      Smoking is associated with more extensive gambling for both low- and high-risk
      adolescent gamblers. CONCLUSION: Smoking may be a marker of more severe gambling
      behaviors in adolescents and important to consider in gambling prevention and
      intervention efforts with youth.

PMID- 25959619
TI  - Tetrodotoxin abruptly blocks excitatory neurotransmission in mammalian CNS.
AB  - The present study utilised a 'synaptic bouton' preparation of mechanically
      isolated rat hippocampal CA3 pyramidal neurons, which permits direct
      physiological and pharmacological quantitative analyses at the excitatory and
      inhibitory single synapse level. Evoked excitatory and inhibitory postsynaptic
      currents (eEPSCs and eIPSCs) were generated by focal paired-pulse electrical
      stimulation of single boutons. The sensitivity of eEPSC to tetrodotoxin (TTX) was
      higher than that of the voltage-dependent Na(+) channel whole-cell current (INa)
      in the postsynaptic CA3 soma membrane. The synaptic transmission was strongly
      inhibited by 3 nM TTX, at which concentration the INa was hardly suppressed. The
      IC50 values of eEPSC and INa for TTX were 2.8 and 37.9 nM, respectively, and
      complete inhibition was 3-10 nM for eEPSC and 1000 nM for INa. On the other hand,
      both eEPSC and eIPSC were equally and gradually inhibited by decreasing the
      external Na(+) concentration ([Na]o), which decreases the Na(+)gradient across
      the cell membrane. The results indicate that TTX at 3-10 nM could block most of
      voltage-dependent Na(+) channels on presynaptic nerve terminal, resulting in
      abruptly inhibition of action potential dependent excitatory neurotransmission.

PMID- 25959618
TI  - Integrating frequency and magnitude information in decision-making in
      schizophrenia: An account of patient performance on the Iowa Gambling Task.
AB  - BACKGROUND: The Iowa Gambling Task (IGT; Bechara et al., 1994) has frequently
      been used to assess risky decision making in clinical populations, including
      patients with schizophrenia (SZ). Poor performance on the IGT is often attributed
      to reduced sensitivity to punishment, which contrasts with recent findings from
      reinforcement learning studies in schizophrenia. METHODS: In order to investigate
      possible sources of IGT performance deficits in SZ patients, we combined data
      from the IGT from 59 SZ patients and 43 demographically-matched controls with
      data from the Balloon Analog Risk Task (BART) in the same participants. Our
      analyses sought to specifically uncover the role of punishment sensitivity and
      delineate the capacity to integrate frequency and magnitude information in
      decision-making under risk. RESULTS: Although SZ patients, on average, made more
      choices from disadvantageous decks than controls did on the IGT, they avoided
      decks with frequent punishments at a rate similar to controls. Patients also
      exhibited excessive loss-avoidance behavior on the BART. CONCLUSIONS: We argue
      that, rather than stemming from reduced sensitivity to negative consequences,
      performance deficits on the IGT in SZ patients are more likely the result of a
      reinforcement learning deficit, specifically involving the integration of
      frequencies and magnitudes of rewards and punishments in the trial-by-trial
      estimation of expected value.

PMID- 25959622
TI  - Kinetic resolution of 2,3-epoxy 3-aryl ketones via catalytic asymmetric ring
      opening with pyrazole derivatives.
AB  - A highly efficient catalytic kinetic resolution of 2,3-epoxy 3-aryl ketones via
      asymmetric ring-opening with pyrazole derivatives has been achieved by using a
      chiral N,N'-dioxide-Sc(III) complex as the catalyst. A wide variety of substrates
      were readily scoped, and the selectivity factors obtained were excellent (up to
      >300).

PMID- 25959621
TI  - Instant coffee extract with high chlorogenic acids content inhibits hepatic G-6
      Pase in vitro, but does not reduce the glycaemia.
AB  - Coffee is the main source of chlorogenic acid in the human diet, and it contains
      several chlorogenic acid isomers, of which the 5-caffeoylquinic acid (5-CQA) is
      the predominant isomer. Because there are no available data about the action of
      chlorogenic acids from instant coffee on hepatic glucose-6-phosphatase (G-6-Pase)
      activity and blood glucose levels, these effects were investigated in rats. The
      changes on G-6-Pase activity and liver glucose output induced by 5-CQA were also
      investigated. Instant coffee extract with high chlorogenic acids content (37.8%)
      inhibited (p < 0.05) the G-6-Pase activity of the hepatocyte microsomal fraction
      in a dose-dependent way (up to 53), but IV administration of this extract did not
      change the glycaemia (p > 0.05). Similarly, 5-CQA (1 mM) reduced (p < 0.05) the
      activity of microsomal G-6-Pase by about 40%, but had no effect (p > 0.05) on
      glucose output arising from glycogenolysis in liver perfusion. It was concluded
      that instant coffee extract with high content of chlorogenic acids inhibited
      hepatic G-6-Pase in vitro, but failed to reduce the glycaemia probably because
      the coffee chlorogenic acids did not reach enough levels within the hepatocytes
      to inhibit the G-6-Pase and reduce the liver glucose output.

PMID- 25959620
TI  - Right parietal cortex mediates recognition memory for melodies.
AB  - Functional brain imaging studies have highlighted the significance of right
      lateralized temporal, frontal and parietal brain areas for memory for melodies.
      The present study investigated the involvement of bilateral posterior parietal
      cortices (PPCs) for the recognition memory of melodies using transcranial direct
      current stimulation (tDCS). Participants performed a recognition task before and
      after tDCS. The task included an encoding phase (12 melodies), a retention
      period, as well as a recognition phase (24 melodies). Experiment 1 revealed that
      anodal tDCS over the right PPC led to a deterioration of overall memory
      performance compared with sham. Experiment 2 confirmed the results of Experiment
      1 and further showed that anodal tDCS over the left PPC did not show a modulatory
      effect on memory task performance, indicating a right lateralization for musical
      memory. Furthermore, both experiments revealed that the decline in memory for
      melodies can be traced back to an interference of anodal stimulation on the
      recollection process (remember judgements) rather than to familiarity judgements.
      Taken together, this study revealed a causal involvement of the right PPC for
      memory for melodies and demonstrated a key role for this brain region in the
      recollection process of the memory task. 

PMID- 25959623
TI  - Effects of water turbulence on variations in cell ultrastructure and metabolism
      of amino acids in the submersed macrophyte, Elodea nuttallii (Planch.) H. St.
      John.
AB  - The interactions between macrophytes and water movement are not yet fully
      understood, and the causes responsible for the metabolic and ultrastructural
      variations in plant cells as a consequence of turbulence are largely unknown. In
      the present study, growth, metabolism and ultrastructural changes were evaluated
      in the aquatic macrophyte Elodea nuttallii, after exposure to turbulence for 30
      days. The turbulence was generated with a vertically oscillating horizontal grid.
      The turbulence reduced plant growth, plasmolysed leaf cells and strengthened cell
      walls, and plants exposed to turbulence accumulated starch granules in stem
      chloroplasts. The size of the starch granules increased with the magnitude of the
      turbulence. Using capillary electrophoresis-mass spectrometry (CE-MS), analysis
      of the metabolome found metabolite accumulation in response to the turbulence.
      Asparagine was the dominant amino acid that was concentrated in stressed plants,
      and organic acids such as citrate, ascorbate, oxalate and gamma-amino butyric
      acid (GABA) also accumulated in response to turbulence. These results indicate
      that turbulence caused severe stress that affected plant growth, cell
      ultrastructure and some metabolic functions of E. nuttallii. Our findings offer
      insights to explain the effects of water movement on the functions of aquatic
      plants.

PMID- 25959624
TI  - Visible mechanochromic responses of spiropyrans in crystals via pressure-induced
      isomerization.
AB  - The isomerization of spiropyrans in crystals was realized under high pressure,
      and the corresponding mechanochromic response could be observed by the naked eye.
      In situ UV-Vis spectroscopy study demonstrated that the equilibrium constant
      increases with the increasing pressure, from which we proposed that the negative
      volume of reaction determined the isomerization under high pressure. 

PMID- 25959625
TI  - Roles of transition metals interchanging with lithium in electrode materials.
AB  - Roles of antisite transition metals interchanging with Li atoms in electrode
      materials of Li transition-metal complex oxides were clarified using a newly
      developed direct labeling method, termed powder diffraction anomalous fine
      structure (P-DAFS) near the Ni K-edge. We site-selectively investigated the
      valence states and local structures of Ni in Li0.89Ni1.11O2, where Ni atoms
      occupy mainly the NiO2 host-layer sites and partially the interlayer Li sites in
      between the host layers, during electrochemical Li insertion/extraction in a
      lithium-ion battery (LIB). The site-selective X-ray near edge structure evaluated
      via the P-DAFS method revealed that the interlayer Ni atoms exhibited much lower
      electrochemical activity as compared to those at the host-layer site.
      Furthermore, the present analyses of site-selective extended X-ray absorption
      fine structure performed using the P-DAFS method indicates local structural
      changes around the residual Ni atoms at the interlayer space during the initial
      charge; it tends to gather to form rock-salt NiO-like domains around the
      interlayer Ni. The presence of the NiO-like domains in the interlayer space
      locally diminishes the interlayer distance and would yield strain energy because
      of the lattice mismatch, which retards the subsequent Li insertion both
      thermodynamically and kinetically. Such restrictions on the Li insertion
      inevitably make the NiO-like domains electrochemically inactive, resulting in an
      appreciable irreversible capacity after the initial charge but an achievement of
      robust linkage of neighboring NiO2 layers that tend to be dissociated without the
      Li occupation. The P-DAFS characterization of antisite transition metals
      interchanging with Li atoms complements the understanding of the detailed charge
      compensation and degradation mechanisms in the electrode materials. 

PMID- 25959626
TI  - Wnt co-receptor LRP5/6 overexpression confers protection against hydrogen
      peroxide-induced neurotoxicity and reduces tau phosphorylation in SH-SY5Y cells.
AB  - Emerging studies have suggested the involvement of dysregulated Wnt/beta-catenin
      cascade in the etiology of Alzheimer's disease (AD). Recently, genetic variations
      in Wnt co-receptor low density lipoprotein receptor-related protein (LRP) 6
      causing reduced Wnt signaling has been linked to late-onset AD. Here, we
      hypothesized that overexpression of Wnt co-receptors LRP5 and LRP6 would serve as
      an effective new approach in reducing neurotoxicity induced by oxidative stress
      and decreasing tau phosphorylation in SH-SY5Y human neuroblastoma cells. Our
      results showed that overexpression of LRP5 and LRP6 in SH-SY5Y cells activates
      Wnt signaling and downstream proliferation genes, whereas knockdown of the co
      receptors represses Wnt signaling and the transcription of proliferative markers.
      We further demonstrated that overexpression of LRP5 and LRP6 protects SH-SY5Y
      from cell death caused by hydrogen peroxide-induced oxidative stress, inhibits
      GSK3beta activity and subsequently reduces tau phosphorylation. Together, our
      findings suggest that rescuing LRP5/6-mediated Wnt signaling improves neuronal
      cell survival and reduces tau phosphorylation, which support the hypothesis that
      Wnt signaling might be an attractive therapeutic strategy for managing AD. 

PMID- 25959627
TI  - Effect of perinatally supplemented flavonoids on brain structure, circulation,
      cognition, and metabolism in C57BL/6J mice.
AB  - Evidence suggests that flavanol consumption can beneficially affect cognition in
      adults, but little is known about the effect of flavanol intake early in life.
      The present study aims to assess the effect of dietary flavanol intake during the
      gestational and postnatal period on brain structure, cerebral blood flow (CBF),
      cognition, and brain metabolism in C57BL/6J mice. Female wild-type C57BL/6J mice
      were randomly assigned to either a flavanol supplemented diet or a control diet
      at gestational day 0. Male offspring remained on the corresponding diets
      throughout life and performed cognitive and behavioral tests during puberty and
      adulthood assessing locomotion and exploration (Phenotyper and open field),
      sensorimotor integration (Rotarod and prepulse inhibition), and spatial learning
      and memory (Morris water maze, MWM). Magnetic resonance spectroscopy and imaging
      at 11.7T measured brain metabolism, CBF, and white and gray matter integrity in
      adult mice. Biochemical and immunohistochemical analyses evaluated inflammation,
      synaptic plasticity, neurogenesis, and vascular density. Cognitive and behavioral
      tests demonstrated increased locomotion in Phenotypers during puberty after
      flavanol supplementation (p = 0.041) but not in adulthood. Rotarod and prepulse
      inhibition demonstrated no differences in sensorimotor integration. Flavanols
      altered spatial learning in the MWM in adulthood (p = 0.039), while spatial
      memory remained unaffected. Additionally, flavanols increased diffusion coherence
      in the visual cortex (p = 0.014) and possibly the corpus callosum (p = 0.066) in
      adulthood. Mean diffusion remained unaffected, a finding that corresponds with
      our immunohistochemical data showing no effect on neurogenesis, synaptic
      plasticity, and vascular density. However, flavanols decreased CBF in the cortex
      (p = 0.001) and thalamus (p = 0.009) in adulthood. Brain metabolite levels and
      neuroinflammation remained unaffected by flavanols. These data suggest that
      dietary flavanols results in subtle alterations in brain structure, locomotor
      activity and spatial learning. Comparison of these data to published findings in
      aging or neurodegeneration suggests that benefits of dietary flavanols may
      increase with advancing age and in disease. 

PMID- 25959629
TI  - Ceftibuten-containing agar plate for detecting group B streptococci with reduced
      penicillin susceptibility (PRGBS).
AB  - Penicillins remain first-line agents for treatment of group B Streptococcus
      (Streptococcus agalactiae; GBS) infections; however, several reports have
      confirmed the existence of GBS with reduced penicillin susceptibility (PRGBS).
      Because no selective agar plates for detection of PRGBS are available to date, in
      this investigation, we developed the selective agar plate for detection of PRGBS.
      We used 19 genetically well-confirmed PRGBS isolates and 38 penicillin
      susceptible GBS isolates identified in Japan. For preparation of trial PRGBS
      selective agar plates, we added 1 of antimicrobial agents (among oxacillin,
      ceftizoxime, and ceftibuten) to a well-established GBS-selective agar plate.
      Among 12 trial PRGBS-selective agar plates, Muller-Hinton agar containing 128
      MUg/mL ceftibuten with 5% sheep blood, 8 MUg/mL gentamicin, and 12 MUg/mL
      nalidixic acid was the most appropriate selective agar for PRGBS, showing 100%
      sensitivity and 81.6% specificity. In cases of potential nosocomial spread of
      PRGBS, the selective agar plate could be useful and reliable.

PMID- 25959630
TI  - N-protected 1,2-oxazetidines as a source of electrophilic oxygen: straightforward
      access to benzomorpholines and related heterocycles by using a reactive tether.
AB  - A hitherto unknown reactivity of a strained four-membered heterocycle, 1,2
      oxazetidine, is reported. When reacted with organometallic compounds, this
      reagent provides electrophilic oxygen with a nitrogen-terminated two-carbon-atom
      tether. The synthetic versatility of the products obtained was demonstrated in
      various transformations, leading to efficient synthesis of six-, seven-, and
      eight-membered heterocyclic systems of pharmaceutical importance. 

PMID- 25959628
TI  - Increased infection with key periodontal pathogens during gestational diabetes
      mellitus.
AB  - AIM: Gestational diabetes mellitus (GDM), gingivitis, infection with specific
      periodontal pathogens and systemic inflammation each increase the risk for poor
      pregnancy outcome. We set out to monitor the interactions of gingivitis and GDM
      with respect to oral infection and the systemic inflammatory burden. MATERIALS
      AND METHODS: Four case-control groups (n = 117) were recruited, (1) No
      gingivitis, No GDM (n = 27); (2) Gingivitis, No GDM (n = 31); (3) No gingivitis,
      GDM (n = 21); and (4) Gingivitis, GDM (n = 38). Oral infection with three key
      periodontal pathogens was determined by PCR. Systemic inflammation was determined
      by quantification of CRP by EIA. RESULTS: Gingivitis during pregnancy was
      associated with oral infection with Porphyromonas gingivalis, Filifactor alocis
      and Treponema denticola and combinations thereof (all p < 0.01). GDM was also
      associated with increased infection with individual and multiple oral pathogens
      (all p < 0.05). Gingivitis during pregnancy led to a 325% increase in systemic
      CRP (mean, 2495 versus 8116 ng/ml, p < 0.01). CONCLUSIONS: Diabetes and
      gingivitis act in concert to increase risk biomarkers for poor pregnancy outcome.

PMID- 25959632
TI  - Palladium-catalyzed hydroaminocarbonylation of alkenes with amines: a strategy to
      overcome the basicity barrier imparted by aliphatic amines.
AB  - A novel and efficient palladium-catalyzed hydroaminocarbonylation of alkenes with
      aminals has been developed under mild reaction conditions, and allows the
      synthesis of a wide range of N-alkyl linear amides in good yields with high
      regioselectivity. On the basis of this method, a cooperative catalytic system
      operating by the synergistic combination of palladium, paraformaldehyde, and acid
      was established for promoting the hydroaminocarbonylation of alkenes with both
      aromatic and aliphatic amines, which do not react well under conventional
      palladium-catalyzed hydroaminocarbonylation. 

PMID- 25959633
TI  - The psychophysiology of mixed emotional states: Internal and external
      replicability analysis of a direct replication study.
AB  - The replicability of emotion-related physiological changes constitutes a
      fundamental issue in affective science. We undertook a direct replication of the
      physiological differentiation of amusement, disgust, and a mixed emotional state
      as previously reported (Kreibig, Samson, & Gross, 2013). In the current study, 48
      women watched 54 amusing, disgusting, and mixed emotional film clips while
      cardiovascular, electrodermal, and respiratory measures were obtained. Primary
      analyses indicated physiological differentiation of the mixed emotional state
      from amusement and disgust. We evaluated (a) the probability that future
      replications of the current study would yield similar results using bootstrapped
      confidence intervals of effect sizes, and (b) the stability of results of
      physiological reactivity between actual replications using correlation and
      regression analyses. Findings suggest replicable differentiation of amusement,
      disgust, and a mixed emotional state. 

PMID- 25959631
TI  - Pharmacokinetics of tenofovir during pregnancy and postpartum.
AB  - OBJECTIVES: Tenofovir disoproxil fumarate (TDF) is increasingly used in the
      highly active antiretroviral therapy (HAART) regimens of pregnant women, but
      limited data exist on the pregnancy pharmacokinetics of chronically dosed TDF.
      This study described tenofovir pharmacokinetics during pregnancy and postpartum.
      METHODS: International Maternal Pediatric and Adolescent AIDS Clinical Trials
      (IMPAACT) P1026s is a prospective, nonblinded pharmacokinetic study of HIV
      infected pregnant women that included a cohort receiving 300 mg TDF once daily.
      Steady-state 24-hour pharmacokinetic profiles were measured at the second and
      third trimesters, postpartum, and in maternal and umbilical cord samples
      collected at delivery. Tenofovir was measured by liquid chromatography-mass
      spectrometry (LC-MS). The target area under the concentration versus time curve
      from time 0 to 24 h post dose (AUC) was >= 1.99 MUg h/mL (nonpregnant historical
      control 10th percentile). RESULTS: The median tenofovir AUC was decreased during
      the second (1.9 MUg h/mL) and third (2.4 MUg h/mL; P = 0.005) trimesters versus
      postpartum (3.0 MUg h/mL). Tenofovir AUC exceeded the target for two of four
      women (50%) in the second trimester, 27 of 37 women [73%; 95% confidence interval
      (CI) 56%, 86%] in the third trimester, and 27 of 32 women (84%; 95% CI 67%, 95%)
      postpartum (P > 0.05). Median second/third-trimester troughs were lower (39/54
      ng/mL) than postpartum (61 ng/mL). Median third-trimester weight was greater for
      subjects below the target AUC versus those above the target (97.9 versus 74.2 kg,
      respectively; P = 0.006). The median ratio of cord blood to maternal
      concentrations was 0.88. No infants were HIV infected. CONCLUSIONS: This study
      found lower tenofovir AUC and troughs during pregnancy. Transplacental passage
      with chronic TDF use during pregnancy was high. Standard TDF doses appear to be
      appropriate for most HIV-infected pregnant women but therapeutic drug monitoring
      with dose adjustment should be considered in pregnant women with high weight (>
      90 kg) or inadequate HIV RNA response.

PMID- 25959635
TI  - Small studies are more heterogeneous than large ones: a meta-meta-analysis.
AB  - OBJECTIVES: Between-study heterogeneity plays an important role in random-effects
      models for meta-analysis. Most clinical trials are small, and small trials are
      often associated with larger effect sizes. We empirically evaluated whether there
      is also a relationship between trial size and heterogeneity (tau). STUDY DESIGN
      AND SETTING: We selected the first meta-analysis per intervention review of the
      Cochrane Database of Systematic Reviews Issues 2009-2013 with a dichotomous (n =
      2,009) or continuous (n = 1,254) outcome. The association between estimated tau
      and trial size was evaluated across meta-analyses using regression and within
      meta-analyses using a Bayesian approach. Small trials were predefined as those
      having standard errors (SEs) over 0.2 standardized effects. RESULTS: Most meta
      analyses were based on few (median 4) trials. Within the same meta-analysis, the
      small study tauS(2) was larger than the large-study tauL(2) [average ratio 2.11;
      95% credible interval (1.05, 3.87) for dichotomous and 3.11 (2.00, 4.78) for
      continuous meta-analyses]. The imprecision of tauS was larger than of tauL:
      median SE 0.39 vs. 0.20 for dichotomous and 0.22 vs. 0.13 for continuous small
      study and large-study meta-analyses. CONCLUSION: Heterogeneity between small
      studies is larger than between larger studies. The large imprecision with which
      tau is estimated in a typical small-studies' meta-analysis is another reason for
      concern, and sensitivity analyses are recommended.

PMID- 25959634
TI  - Time-dependent biodistribution, clearance and biocompatibility of magnetic fibrin
      nanoparticles: an in vivo study.
AB  - Recently, bioretention and toxicity of injected nanoparticles in the body has
      drawn much attention in biomedical research. In the present study, 5 mg Fe per kg
      body weight of magnetic fibrin nanoparticles (MFNPs) were injected into mice
      intravenously and investigated for their blood clearance profile,
      biodistribution, haematology and pathology studies for a time period of 28 days.
      Moderately long circulation of MFNPs in blood was observed with probable
      degradation and excretion into the bloodstream via monoatomic iron forms.
      Inductively coupled plasma optical emission spectrometry (ICP-OES) and Prussian
      blue staining results showed increased accumulation of MFNPs in the liver,
      followed by spleen and other organs. Body weight, spleen/thymus indexes,
      haematology, serum biochemistry and histopathology studies demonstrated that
      MFNPs were biocompatible. These results suggest the feasibility of using MFNPs
      for drug delivery and imaging applications. 

PMID- 25959636
TI  - Healthcare costs and resource utilization of patients with binge-eating disorder
      and eating disorder not otherwise specified in the Department of Veterans
      Affairs.
AB  - OBJECTIVE: The objective of this study was to compare the one-year healthcare
      costs and utilization of patients with binge-eating disorder (BED) to patients
      with eating disorder not otherwise specified without BED (EDNOS-only) and to
      matched patients without an eating disorder (NED). METHODS: A natural language
      processing (NLP) algorithm identified adults with BED from clinical notes in the
      Department of Veterans Affairs (VA) electronic health record database from 2000
      to 2011. Patients with EDNOS-only were identified using ICD-9 code (307.50) and
      those with NLP-identified BED were excluded. First diagnosis date defined the
      index date for both groups. Patients with NED were randomly matched 4:1, as
      available, to patients with BED on age, sex, BMI, depression diagnosis, and index
      month. Patients with cost data (2005-2011) were included. Total healthcare,
      inpatient, outpatient, and pharmacy costs were examined. Generalized linear
      models were used to compare total one-year healthcare costs while adjusting for
      baseline patient characteristics. RESULTS: There were 257 BED, 743 EDNOS-only,
      and 823 matched NED patients identified. The mean (SD) total unadjusted one-year
      costs, in 2011 US dollars, were $33,716 ($38,928) for BED, $37,052 ($40,719) for
      EDNOS-only, and $19,548 ($35,780) for NED patients. When adjusting for patient
      characteristics, BED patients had one-year total healthcare costs $5,589 higher
      than EDNOS-only (p = 0.06) and $18,152 higher than matched NED patients (p <
      0.001). DISCUSSION: This study is the first to use NLP to identify BED patients
      and quantify their healthcare costs and utilization. Patients with BED had
      similar one-year total healthcare costs to EDNOS-only patients, but significantly
      higher costs than patients with NED.

PMID- 25959637
TI  - [Complications associated to central venous catheters in hematology patients].
AB  - OBJECTIVE: To discover the incidence of central venous catheters (tunnelled,
      subcutaneous and PICC) in patients with onco-hematological conditions,
      hospitalized in the Hematology or Transplantations of Hematopoietic Stem Cells
      Units, in two tertiary care hospitals. METHODOLOGY: A cross-sectional,
      descriptive study form was developed in order to gather sociodemographic,
      clinical data as well as complications and follow-up of the care protocol. Each
      catheter was assigned a correlative identification number. Information was
      collected on 366 catheters: 185 in the University Hospital Ramon y Cajal (HURYC),
      80 tunnelled, 40 subcutaneous venous access and 65 PICC, and 181 in the
      University Hospital Gregorio Maranon (HUGM), 101 tunnelled and 80 subcutaneous
      venous access. FINDINGS: Major complications in the tunnellized were infections
      (13.7% in HURYC vs. 6.8% in HUGM - p<0.001) and occlusions (at least once in 3.8%
      vs. 21.8%). In subcutaneous venous access, infections were confirmed in 5% in
      HURYC vs. 1.2% in HUGM. There were occlusions at least once in 10% in HUGM and no
      other significant complications were detected. Regarding PICC, information was
      only collected in HURYC, where complications were phlebitis 10.8%, thrombosis
      7.7%, confirmed or suspected infection 4.6%, occlusion at least once 7.7%.
      CONCLUSIONS: Differences between hospitals with regard to major complications,
      infection and occlusion may be related to different care protocol. We need to
      stress the high incidence of phlebitis and thrombosis in PICC catheters, compared
      with data of lower incidence of other papers.

PMID- 25959638
TI  - [Reliability of nursing outcomes classification label "Knowledge: cardiac disease
      management (1830)" in outpatients with heart failure].
AB  - OBJECTIVE: To determine the reliability (internal consistency, inter-rater
      reproducibility and level of agreement) of nursing outcome: "Knowledge: cardiac
      disease management (1830)" of the version published in Spanish, in outpatients
      with heart failure. METHODS: A reliability study was conducted on 116 outpatients
      with heart failure. Six indicators of nursing outcome were operationalized. All
      participants were assessed simultaneously by two evaluators. Three evaluation
      periods were defined: initial (at baseline), final (a month later), and follow-up
      (two months later). STATISTICAL ANALYSIS: Internal consistency by Cronbach alpha
      coefficient, inter-rater reproducibility with intraclass correlation coefficient
      of reproducibility or agreement and level agreement using the 95% limits of Bland
      and Altman. RESULTS: Cronbach's alpha was 0.83 (95% CI: 0.77 - 0.89) in the final
      evaluation, and follow-up values of 0.85 (95% CI: 0.82-0.89) and 0.83 (95% CI:
      0.78 - 0.88) were found for the first and second evaluator, respectively. The
      intraclass correlation coefficient showed values greater 0.9 in the three
      evaluation periods in both the random and mixed model. The Bland-Altman 95%
      limits of agreement were close to zero in the three evaluations performed.
      CONCLUSIONS: The questionnaire operationalized to assess the nursing outcome:
      "Knowledge: cardiac disease management (1830)" in its Spanish version, is a
      reliable method to measure skills and knowledge in outpatients with heart failure
      in the Colombian context.

PMID- 25959639
TI  - Efficient and stable planar heterojunction perovskite solar cells with an
      MoO3/PEDOT:PSS hole transporting layer.
AB  - A solution processed MoO3/PEDOT:PSS bilayer structure is used as the hole
      transporting layer to improve the efficiency and stability of planar
      heterojunction perovskite solar cells. Increased hole extraction efficiency and
      restrained erosion of ITO by PEDOT: PSS are demonstrated in the optimized device
      due to the incorporation of an MoO3 layer.

PMID- 25959640
TI  - Could a dye offer a cheap and simple approach to detect bladder cancer using
      white-light cystoscopy?

PMID- 25959641
TI  - The impact of masticatory ability as evaluated by salivary flow rates on obesity
      in Japanese: The Toon health study.
AB  - OBJECTIVE: This study examined the associations of masticatory ability evaluated
      by chewing-gum-stimulated salivary flow rate with anthropometric indices among a
      general Japanese population. METHODS: In total, 921 Japanese men and women aged
      30-79 years participated in this cross-sectional study. Saliva production was
      stimulated by 5 min of gum chewing, then collected; salivary flow rate was
      calculated as g/min. Overweight, abdominal obesity in terms of waist
      circumference (WC), and waist-hip ratio (WHR), and elevated skinfold thickness
      statuses were determined. RESULTS: The multivariable odds ratio and 95%
      confidence intervals of overweight, abdominal obesity (WC, WHR), and elevated
      skinfold thickness status for highest vs. lowest quartile of salivary flow rate
      were 0.59 (0.37-0.95, P for trend = 0.02), 0.65 (0.43-0.98, P = 0.03), 0.54 (0.35
      0.83, P < 0.01), and 0.61 (0.39-0.96, P < 0.01), respectively. The linear trends
      of multivariable-adjusted means of BMI, WC, WHR, and skinfold thickness according
      to quartiles of salivary flow rate did not vary after stratification by
      overweight status. CONCLUSIONS: Higher stimulated salivary flow rate, a surrogate
      marker for mastication ability, was associated with lower prevalence of
      overweight, abdominal obesity (whether WC- or WHR-defined), and elevated skinfold
      thickness among the general Japanese population.

PMID- 25959642
TI  - Exhaled breath analysis by electronic nose in respiratory diseases.
AB  - Breath analysis via electronic nose is a technique oriented around volatile
      organic compound (VOC) profiling in exhaled breath for diagnostic and prognostic
      purposes. This approach, when supported by methodologies for VOC identification,
      has been often referred to as metabolomics or breathomics. Although breath
      analysis may have a substantial impact on clinical practice, as it may allow
      early diagnosis and large-scale screening strategies while being noninvasive and
      inexpensive, some technical and methodological limitations must be solved,
      together with crucial interpretative issues. By integrating a review of the
      currently available literature with more speculative arguments about the
      potential interpretation and application of VOC analysis, the authors aim to
      provide an overview of the main relevant aspects of this promising field of
      research. 

PMID- 25959643
TI  - Partial protection and abomasal cytokine expression in sheep experimentally
      infected with Haemonchus contortus and pre-treated with Taenia hydatigena
      vesicular concentrate.
AB  - The abomasal expression of IL-2, IL-4, IL-6, IL-10 and IFNgamma in lambs
      experimentally infected with Haemonchus contortus and its relationship to
      protection induced by a Taenia hydatigena larvae vesicular concentrate (ThLVC)
      were evaluated. The lambs that were only infected with H. contortus larvae showed
      a worm burden greater (p<0.05) than the lambs that received ThLVC prior to
      infection. Moreover, the lambs that received ThLVC showed a greater (p<0.05)
      number of blood eosinophils than the lambs that did not receive the ThLVC. In
      general, the lambs that received ThLVC prior to infection had a greater amount of
      eosinophils and mast cells and higher in situ expression of IFNgamma, IL-2, IL-4,
      IL-6 and IL-10 in the abomasal wall than the lambs that were infected with H.
      contortus only or that received ThLVC (p<0.05) only. A higher expression of IL-2
      and IFNgamma in the submucosa compared to the abomasal mucosa and a higher
      expression of IL-4 in the abomasal mucosa compared to the submucosa was observed
      (p<0.05). These results suggest that there is a Th1 type response in the abomasal
      submucosa and a Th2 type response in in the abomasal mucosa. The amount of
      eosinophils and mast cells and the in situ expression of IFNgamma, IL-2, IL-4 and
      IL-6 in the abomasal walls were negatively correlated with the worm burden
      (p<0.05). These results suggest that ThLVC is a non-specific immune stimulator
      for the abomasal immune response, and it is likely that the protection observed
      is the result of this effect. 

PMID- 25959644
TI  - Not only for the risk of bone fracture.

PMID- 25959645
TI  - Clinical and cost-effectiveness of insulin degludec: from clinical trials to
      clinical practice.
AB  - The increasing prevalence of diabetes presents one of the greatest challenges to
      healthcare provision in modern times, with the cost of treating diabetes and its
      related complications representing a significant proportion of healthcare
      expenditure. In recent years, many new therapeutic entities have been developed
      with the aim of improving glycemic control, and thus slowing the development of
      micro- and macrovascular complications. Insulin degludec is a new-generation
      basal insulin analog with an ultra-long duration of action and low day-to-day and
      hour-to-hour intrapatient variability in blood glucose-lowering action. In this
      review, we consider evidence from clinical trials and real-world studies
      demonstrating the clinical benefits and cost-effectiveness of insulin degludec
      and its potential for improving patient care.

PMID- 25959647
TI  - Low barriers for hydrogen diffusion in sII clathrate.
AB  - The transport of gas molecules in hydrates is presently poorly understood. In sII
      structured hydrates with hydrogen guests there is, for instance, a mismatch
      between experimental and computed values for diffusion constants. We provide an
      explanation for the experimentally observed diffusion rates, using DFT-based
      molecular dynamics simulations at 100 K. By considering the effect of cage
      occupancy, as well as the flexibility of the water lattice, we show that barriers
      for hydrogen diffusing between cages, can approach values as low as 5 kJ mol(-1),
      which is very close to experimental values. 

PMID- 25959646
TI  - Gene loss in keratinization programs accompanies adaptation of cetacean skin to
      aquatic lifestyle.

PMID- 25959648
TI  - Matrix factorization from non-linear projections: application in estimating T2
      maps from few echoes.
AB  - This work addresses the problem of estimating T2 maps from very few (two) echoes.
      Existing multi-parametric non-linear curve fitting techniques require a large
      number (16 or 32) of echoes to estimate T2 values. We show that our method yields
      very accurate and robust results from only two echoes, where as the curve-fitting
      techniques require about 16 echoes to achieve the same level of accuracy. We
      model T2 maps as a rank-deficient matrix. Since the relationship between T2
      values and intensity values/K-space samples is not linear, estimating the T2
      values requires recovering a low-rank matrix from non-linear projections. We
      solve this as a non-linear matrix factorization problem. Since the said problem
      has not been solved before, we propose a simple algorithm for the same. 

PMID- 25959650
TI  - Folic acid-polydopamine nanofibers show enhanced ordered-stacking via pi-pi
      interactions.
AB  - Recent research has indicated that polydopamine and synthetic eumelanins are
      optoelectronic biomaterials in which one-dimensional aggregates composed of
      ordered-stacking oligomers have been proposed as unique organic semiconductors.
      However, improving the ordered-stacking of oligomers in polydopamine
      nanostructures is a big challenge. Herein, we first demonstrate how folic acid
      molecules influence the morphology and nanostructure of polydopamine via tuning
      the pi-pi interactions of oligomers. MALDI-TOF mass spectrometry reveals that
      porphyrin-like tetramers are characteristic of folic acid-polydopamine (FA-PDA)
      nanofibers. X-ray diffraction combined with simulation studies indicate that
      these oligomers favour aggregation into graphite-like ordered nanostructures via
      strong pi-pi interactions. High-resolution TEM characterization of carbonized FA
      PDA hybrids show that in FA-PDA nanofibers the size of the graphite-like domains
      is over 100 nm. The addition of folic acid in polydopamine enhances the ordered
      stacking of oligomers in its nanostructure. Our study steps forward to discover
      the mystery of the structure-property relationship of FA-PDA hybrids. It paves a
      way to optimize the properties of PDA through the design and selection of
      oligomer structures. 

PMID- 25959651
TI  - Higher TNFalpha responses in young males compared to females are associated with
      attenuation of monocyte adenylyl cyclase expression.
AB  - Tumor necrosis factor alpha (TNFalpha) expression is strongly attenuated by the
      intracellular signaling mediator cyclic adenosine monophosphate (cAMP), which is
      synthesized by adenylyl cyclase (AC) enzymes. We have compared AC regulation and
      TNFalpha production in male and female monocytes, and characterized the role of
      monocyte AC isoforms in TNFalpha regulation. Males and females, age groups 20-30
      years and 50-70 years donated blood for this study. In lipopolysaccharide
      stimulated blood from young male donors, we observed significantly higher
      TNFalpha responses (6h, p=0.03) compared to females of the same age, a difference
      not observed in the older donors. Rapid down-regulation of the monocyte AC
      isoforms AC4, AC7 and AC9 were observed in young males. AC-directed siRNA
      experiments in the human monocyte cell line THP-1 demonstrated that AC7 and AC9
      knock-down significantly induced TNFalpha release (p=0.01 for both isoforms).
      These data indicate that the stronger TNFalpha-responses in young males may be
      partly associated with male-specific down-regulation of adenylyl cyclases.

PMID- 25959652
TI  - Visualizing the qualitative: making sense of written comments from an evaluative
      satisfaction survey.
AB  - PURPOSE: Satisfaction surveys are common in the field of health education, as a
      means of assisting organizations to improve the appropriateness of training
      materials and the effectiveness of facilitation-presentation. Data can be
      qualitative of which analysis often become specialized. This technical article
      aims to reveal whether qualitative survey results can be visualized by presenting
      them as a Word Cloud. METHODS: Qualitative materials in the form of written
      comments on an agency-specific satisfaction survey were coded and quantified. The
      resulting quantitative data were used to convert comments into "input terms" to
      generate Word Clouds to increase comprehension and accessibility through
      visualization of the written responses. RESULTS: A three-tier display
      incorporated a Word Cloud at the top, followed by the corresponding frequency
      table, and a textual summary of the qualitative data represented by the Word
      Cloud imagery. This mixed format adheres to recognition that people vary in what
      format is most effective for assimilating new information. CONCLUSION: The
      combination of visual representation through Word Clouds complemented by
      quantified qualitative materials is one means of increasing comprehensibility for
      a range of stakeholders, who might not be familiar with numerical tables or
      statistical analyses.

PMID- 25959649
TI  - Detection of hand and leg motor tract injury using novel diffusion tensor MRI
      tractography in children with central motor dysfunction.
AB  - PURPOSE: To examine whether an objective segmenation of corticospinal tract (CST)
      associated with hand and leg movements can be used to detect central motor
      weakness in the corresponding extremities in a pediatric population. MATERIAL AND
      METHODS: This retrospective study included diffusion tensor imaging (DTI) of 25
      children with central paresis affecting at least one limb (age: 9.0+/-4.2years,
      15 boys, 5/13/7 children with left/right/both hemispheric lesions including
      ischemia, cyst, and gliosis), as well as 42 pediatric control subjects with no
      motor dysfunction (age: 9.0+/-5.5years, 21 boys, 31 healthy/11 non-lesional
      epilepsy children). Leg- and hand-related CST pathways were segmented using DTI
      maximum a posteriori (DTI-MAP) classification. The resulting CST volumes were
      then divided by total supratentorial white matter volume, resulting in a marker
      called "normalized streamline volume ratio (NSVR)" to quantify the degree of
      axonal loss in separate CST pathways associated with leg and hand motor
      functions. A receiver operating characteristic curve was applied to measure the
      accuracy of this marker to identify extremities with motor weakness. RESULTS:
      NSVR values of hand/leg CST selectively achieved the following values of
      accuracy/sensitivity/specificity: 0.84/0.84/0.57, 0.82/0.81/0.55, 0.78/0.75/0.55,
      0.79/0.81/0.54 at a cut-off of 0.03/0.03/0.03/0.02 for right hand CST, left hand
      CST, right leg CST, and left leg CST, respectively. Motor weakness of hand and
      leg was most likely present at the cut-off values of hand and leg NSVR (i.e.,
      0.029/0.028/0.025/0.020 for left-hand/right-hand/left-leg/right-leg). The control
      group showed a moderate age-related increase in absolute CST volumes and a
      biphasic age-related variation of the normalized CST volumes, which were lacking
      in the paretic children. CONCLUSIONS: This study demonstrates that DTI-MAP
      classification may provide a new imaging tool to quantify axonal loss in children
      with central motor dysfunction. Using this technique, we found that early-life
      brain lesions affect the maturational trajectory of the primary motor pathway
      which may be used as an effective marker to facilitate evidence-based treatment
      of paretic children.

PMID- 25959653
TI  - Cross-platform digital assessment forms for evaluating surgical skills.
AB  - A variety of structured assessment tools for use in surgical training have been
      reported, but extant assessment tools often employ paper-based rating forms.
      Digital assessment forms for evaluating surgical skills could potentially offer
      advantages over paper-based forms, especially in complex assessment situations.
      In this paper, we report on the development of cross-platform digital assessment
      forms for use with multiple raters in order to facilitate the automatic
      processing of surgical skills assessments that include structured ratings. The
      FileMaker 13 platform was used to create a database containing the digital
      assessment forms, because this software has cross-platform functionality on both
      desktop computers and handheld devices. The database is hosted online, and the
      rating forms can therefore also be accessed through most modern web browsers.
      Cross-platform digital assessment forms were developed for the rating of surgical
      skills. The database platform used in this study was reasonably priced, intuitive
      for the user, and flexible. The forms have been provided online as free downloads
      that may serve as the basis for further development or as inspiration for future
      efforts. In conclusion, digital assessment forms can be used for the structured
      rating of surgical skills and have the potential to be especially useful in
      complex assessment situations with multiple raters, repeated assessments in
      various times and locations, and situations requiring substantial subsequent data
      processing or complex score calculations. 

PMID- 25959654
TI  - Evaluation of hospital-learning environment for pediatric residency in eastern
      region of Saudi Arabia.
AB  - PURPOSE: No study had been conducted to assess the hospitals' environment for
      learning purposes in multicenter sites in Saudi Arabia. It aims to evaluate the
      environment of hospitals for learning purposes of pediatric residents. METHODS:
      We applied Postgraduate Hospital Educational Environment Measure (PHEEM) to
      measure the learning environment at six teaching hospitals in the Eastern Region
      of Saudi Arabia from September to December 2013. RESULTS: The number of
      respondents was 104 (86.7%) out of 120 residents and 37 females and 67 male
      residents have responded. The residents' response scored 100 out of 160 maximum
      score in rating of PHEEM that showed overall learning environment is favorable
      for training. There were some items in the social support domain suggesting
      improvements. There was no significant difference between male and female
      residents. There was a difference among the participant teaching hospitals
      (p<0.05). CONCLUSION: The result pointed an overall positive rating. Individual
      item scores suggested that their social life during residency could be
      uninspiring. They have the low satisfactory level and they feel racism, and
      sexual discrimination. Therefore, there is still a room for improvement.

PMID- 25959655
TI  - Global differences in electronic portfolio utilization - a review of the
      literature and research implications.

PMID- 25959656
TI  - Prenatal genetic care: debates and considerations of the past, present and
      future.
AB  - After karyotyping invasively obtained fetal material for decades, the field of
      prenatal genetic care has changed tremendously since the turn of the century. The
      introduction of novel technologies and strategies went along with concerns and
      debates, in which key issues were costs, the finding of variants of unknown or
      uncertain clinical relevance, commercialization and ethical and social issues. At
      present, there is an explosion of new genomic technologies, which need critical
      assessment prior to implementation, especially in the prenatal field. The key
      issues of the debates we had in the past will again play a major role in guiding
      us toward careful implementation of these new techniques in future. 

PMID- 25959657
TI  - Toward an in-depth profiling of DTC users.

PMID- 25959658
TI  - Selective and Quantitative Oxidation of Xanthate End-Groups of RAFT Poly(n-butyl
      acrylate) Latexes by Ozonolysis.
AB  - Although various successful strategies have been reported in the past for the
      postpolymerization modification of the reversible addition-fragmentation chain
      transfer (RAFT) terminal group in homogeneous media, no solution is proposed for
      the tedious case of aqueous polymer dispersions where most of the
      thiocarbonylthio terminal group is buried into the core of the polymer particle.
      In this work, ozone is proposed to tackle this important academic and industrial
      challenge. After preliminary model ozonolysis reactions performed on a xanthate
      RAFT agent and a derived low molar mass poly(n-butyl acrylate) (PBA) in
      dichloromethane solution, it is shown that the hydrophobic nature and strong
      oxidant properties of ozone are responsible for its efficient diffusion in
      aqueous PBA latex particles obtained by RAFT and selective and complete
      transformation of the xanthate terminal group into a thiocarbonate end-group. In
      addition to the beneficial total discoloration of the final product, this
      chemical treatment does not generate any volatile organic compound and leaves the
      colloidal stability of the polymer particles unaffected, provided that a PBA
      latex with a sufficiently high Mn of 5000 g mol(-1) is selected. 

PMID- 25959659
TI  - Targeting blood thrombogenicity precipitates atherothrombotic events in a mouse
      model of plaque destabilization.
AB  - Although some features of plaque instability can be observed in genetically
      modified mouse models, atherothrombosis induction in mice has been attested to be
      difficult. We sought to test the hypothesis that alterations in blood
      thrombogenicity might have an essential role in the development of
      atherothrombosis in ApoE-/- mice. In a mouse model of plaque destabilization
      established in our laboratory, we targeted blood thrombogenicity by systemically
      overexpressing murine prothrombin via adenovirus-mediated gene transfer. Systemic
      overexpression of prothrombin increased blood thrombogenicity, and remarkably,
      precipitated atherothrombotic events in 70% of the animals. The affected plaques
      displayed features of culprit lesions as seen in human coronary arteries,
      including fibrous cap disruption, luminal thrombosis, and plaque hemorrhage.
      Treatment with aspirin and clopidogrel substantially reduced the incidence of
      atherothrombosis in this model. Mechanistically, increased inflammation,
      apoptosis and upregulation of metalloproteinases contributed to the development
      of plaque destabilization and atherothrombosis. As conclusions, targeting blood
      thrombogenicity in mice can faithfully reproduce the process of atherothrombosis
      as occurring in human coronary vessels. Our results suggest that blood-plaque
      interactions are critical in the development of atherothrombosis in mice,
      substantiating the argument that changes in blood coagulation status may have a
      determinant role in the onset of acute coronary syndrome. 

PMID- 25959660
TI  - Database integration of protocol-specific neurological imaging datasets.
AB  - For many years now, Magnetic Resonance Innovations (MR Innovations), a magnetic
      resonance imaging (MRI) software development, technology, and research company,
      has been aggregating a multitude of MRI data from different scanning sites
      through its collaborations and research contracts. The majority of the data has
      adhered to neuroimaging protocols developed by our group which has helped ensure
      its quality and consistency. The protocols involved include the study of:
      traumatic brain injury, extracranial venous imaging for multiple sclerosis and
      Parkinson's disease, and stroke. The database has proven invaluable in helping to
      establish disease biomarkers, validate findings across multiple data sets,
      develop and refine signal processing algorithms, and establish both public and
      private research collaborations. Myriad Masters and PhD dissertations have been
      possible thanks to the availability of this database. As an example of a project
      that cuts across diseases, we have used the data and specialized software to
      develop new guidelines for detecting cerebral microbleeds. Ultimately, the
      database has been vital in our ability to provide tools and information for
      researchers and radiologists in diagnosing their patients, and we encourage
      collaborations and welcome sharing of similar data in this database. 

PMID- 25959661
TI  - The interference effect in arithmetic fact solving: An fMRI study.
AB  - Some multiplication facts share common digits with other, previously learned
      facts, and as a result, different problems are associated with different levels
      of interference. The detrimental effect of interference in arithmetic facts
      knowledge has been recently highlighted in behavioral studies, in children as
      well as in adults, both in typical and atypical development. The present study
      investigated the brain regions involved in the interference effect when solving
      multiplication problems. Twenty healthy adults carried out a multiplication task
      in an MRI scanner. The event-related design comprised problems whose interference
      level and problem size were manipulated in a 2*2 factorial design. After each
      trial, individuals were requested to indicate whether they solved the trial by
      retrieving the answer from long-term memory. This allowed us to examine which
      brain areas were sensitive to the interference effect and problem size effect as
      well as the retrieval strategy. The results highlighted two specific regions: the
      left angular gyrus was more activated for low interfering than for high
      interfering problems, and the right intraparietal sulcus was more activated for
      large problems than for small problems. In both regions, brain activity was not
      modulated by the other effect. These results suggest that the left angular gyrus
      is sensitive to the level of interference of the multiplication problems, whereas
      previously this region was thought to be more activated by small problems or by
      retrieval strategy. Here, in a design manipulating interference and problem size,
      while controlling for retrieval strategy, we showed that it rather reflects an
      automatic mapping between the problem and the answer stored in long-term memory.
      The right intraparietal sulcus was modulated by the problem size effect, which
      supports the idea that the problem size effect comes from the higher overlap
      between magnitude of the answers of large problems compared to small ones.
      Importantly, neither effects can be reduced to a strategy effect since they were
      present when analyzing only retrieval trials. 

PMID- 25959662
TI  - Osteitis and mucosal inflammation in a rabbit model of sinusitis.
AB  - INTRODUCTION: Several experimental studies have shown osteitis after the onset of
      sinusitis, supporting the idea that bone involvement could participate in the
      dissemination and perpetuation of this inflammatory disease. However, procedures
      commonly performed for the induction of sinusitis, such as antrostomies, can
      trigger sinusitis by themselves. OBJECTIVE: To evaluate osteitis in an animal
      model of sinusitis that does not violate the sinus directly and verify whether
      this is limited to the induction side, or if it affects the contralateral side.
      METHODS: Experimental study in which sinusitis was produced by inserting an
      obstructing sponge into the nasal cavity of 20 rabbits. After defined intervals,
      the animals were euthanized and maxillary sinus samples were removed for semi
      quantitative histological analysis of mucosa and bone. RESULTS: Signs of bone and
      mucosal inflammation were observed, affecting both the induction and
      contralateral sides. Statistical analysis showed correlation between the
      intensity of osteitis on both sides, but not between mucosal and bone
      inflammation on the same side, supporting the theory that inflammation can spread
      through bone structures, regardless of mucosal inflammation. CONCLUSION: This
      study demonstrated that in an animal model of sinusitis that does not disturb the
      sinus directly osteitis occurs in the affected sinus and that it also affects the
      contralateral side.

PMID- 25959663
TI  - Spatially and spectrally engineered spin-orbit interaction for achromatic virtual
      shaping.
AB  - The geometries of objects are deterministic in electromagnetic phenomena in all
      aspects of our world, ranging from imaging with spherical eyes to stealth
      aircraft with bizarre shapes. Nevertheless, shaping the physical geometry is
      often undesired owing to other physical constraints such as aero- and hydro
      dynamics in the stealth technology. Here we demonstrate that it is possible to
      change the traditional law of reflection as well as the electromagnetic
      characters without altering the physical shape, by utilizing the achromatic phase
      shift stemming from spin-orbit interaction in ultrathin space-variant and
      spectrally engineered metasurfaces. The proposal is validated by full-wave
      simulations and experimental characterization in optical wavelengths ranging from
      600 nm to 2800 nm and microwave frequencies in 8-16 GHz, with echo reflectance
      less than 10% in the whole range. The virtual shaping as well as the revised law
      of reflection may serve as a versatile tool in many realms, including broadband
      and conformal camouflage and Kinoform holography, to name just a few. 

PMID- 25959664
TI  - Highly reproducible results of breast cancer biomarkers when analysed in
      accordance with national guidelines - a Swedish survey with central re
      assessment.
AB  - BACKGROUND: Biomarkers are crucial for decisions regarding adjuvant therapy in
      primary breast cancer, and their correct assessment is therefore of the utmost
      importance. AIMS: To investigate the concordance between Swedish pathology
      departments and a reference laboratory, for routine analysis of oestrogen
      receptor (ER), progesterone receptor (PR), Ki67, and human epidermal growth
      factor receptor 2 (HER2), alone, and in combination (St Gallen subtypes).
      METHODS: This survey included 27 of the 28 pathology laboratories in Sweden,
      covering 98% of cases of primary breast cancer surgery in Sweden. Paraffin
      embedded tumour blocks (n = 270) were collected and sent to the central reference
      laboratory, together with the originally stained slides, for re-analysis. The
      primary evaluations were previously performed according to national Swedish
      guidelines, without any knowledge of the subsequent central assessment. RESULTS:
      The agreement for ER, PR, and Ki67 was 99% [kappa value (kappa) = 0.95], 95%
      (kappa = 0.85), and 85% (kappa = 0.70), respectively. The agreement for HER2 (0/1
      + vs. 2+/3+) was 85% (kappa = 0.64), but when equivocal tumours were further
      analysed with in situ hybridisation, only one discrepancy was observed.
      Discrepancies between results for ER and PR seem to be explained by analytical
      differences, whereas the interpretation of staining seems to be more critical for
      Ki67 and HER2 immunohistochemistry. The agreement between the results from the
      Swedish laboratories and the reference laboratory, based on the St Gallen
      subtypes, was 88% (kappa = 0.81). CONCLUSIONS: When applying national guidelines,
      highly reproducible results were obtained in routine assessment of breast cancer
      biomarkers, and the results of this study confirm the clinical utility of these
      markers for decisions regarding the treatment of primary breast cancer.

PMID- 25959665
TI  - Cloning and structural characterization of juvenile hormone diol kinase in
      Spodoptera litura.
AB  - Juvenile hormone (JH) is one of the key insect hormones that regulate
      metamorphosis. Juvenile hormone diol kinase (JHDK) is an enzyme involved in JH
      metabolism and catalyzes JH diol to form a polar end product, JH diol phosphate
      that has no JH activity. In this study, a JHDK complementary DNA (cDNA) was
      cloned from Spodoptera litura and the structure and expression of the gene was
      characterized. The cDNA was 714 base pairs in length and encoded a protein of 183
      amino acids with a molecular mass of 21 kDa and an isoelectric point of 4.55.
      Based on the structure, three putative calcium binding motifs and guanosine
      triphosphate-binding motifs were predicted in the protein. Modeling of the 3-D
      structure showed that the protein consisted of eight alpha-helixes linked with
      loops, with no beta-sheets. The gene was expressed in the epidermis, fat body and
      midgut of fifth and sixth instar larvae. The expression level in the epidermis
      was lower than in the fat body and midgut. The gene was expressed at higher
      levels at the early stages than in the later stages of fifth and sixth instar
      midgut and fat body. The results suggest that this gene may be involved in the
      regulation of the JH titer in larvae of S. litura.

PMID- 25959667
TI  - Unprecedented chi isomers of single-side triol-functionalized Anderson
      polyoxometalates and their proton-controlled isomer transformation.
AB  - The MU2-O atom in Anderson polyoxometalates was regioselectively activated by the
      introduction of protons, which, upon functionalization with triol ligands, could
      afford a series of unique chi isomers of the organically-derived Anderson cluster
      {[RCC(CH2O)3]MMo6O18(OH)3}(3-). Herein proton-controlled isomer transformation
      between the delta and chi isomer was observed by using the fingerprint region in
      the IR spectra and (13)C NMR spectra. 

PMID- 25959666
TI  - Light-Triggered RNA Annealing by an RNA Chaperone.
AB  - Non-coding antisense RNAs regulate bacterial genes in response to nutrition or
      environmental stress, and can be engineered for artificial gene control. The RNA
      chaperone Hfq accelerates antisense pairing between non-coding RNAs and their
      mRNA targets, by a mechanism still unknown. We used a photocaged guanosine
      derivative in an RNA oligonucleotide to temporally control Hfq catalyzed
      annealing. Using a fluorescent molecular beacon as a reporter, we observed RNA
      duplex formation within 15 s following irradiation (3 s) of photocaged RNA
      complexed with Hfq. The results showed that the Hfq chaperone directly stabilizes
      the initiation of RNA base pairs, and suggests a strategy for light-activated
      control of gene expression by non-coding RNAs.

PMID- 25959668
TI  - Sensitization to cashew nut 2S albumin, Ana o 3, is highly predictive of cashew
      and pistachio allergy in Greek children.

PMID- 25959669
TI  - Reply: To PMID 25174863.

PMID- 25959670
TI  - The IL-1 axis is associated with airway inflammation after O3 exposure in
      allergic asthmatic patients.

PMID- 25959671
TI  - Early-onset hypogammaglobulinemia: A survey of 44 patients.

PMID- 25959672
TI  - Nasal endoscopy to characterize sinonasal disease.

PMID- 25959673
TI  - Cooperation between COA6 and SCO2 in COX2 maturation during cytochrome c oxidase
      assembly links two mitochondrial cardiomyopathies.
AB  - Three mitochondria-encoded subunits form the catalytic core of cytochrome c
      oxidase, the terminal enzyme of the respiratory chain. COX1 and COX2 contain heme
      and copper redox centers, which are integrated during assembly of the enzyme.
      Defects in this process lead to an enzyme deficiency and manifest as
      mitochondrial disorders in humans. Here we demonstrate that COA6 is specifically
      required for COX2 biogenesis. Absence of COA6 leads to fast turnover of newly
      synthesized COX2 and a concomitant reduction in cytochrome c oxidase levels. COA6
      interacts transiently with the copper-containing catalytic domain of newly
      synthesized COX2. Interestingly, similar to the copper metallochaperone SCO2,
      loss of COA6 causes cardiomyopathy in humans. We show that COA6 and SCO2 interact
      and that corresponding pathogenic mutations in each protein affect complex
      formation. Our analyses define COA6 as a constituent of the mitochondrial copper
      relay system, linking defects in COX2 metallation to cardiac cytochrome c oxidase
      deficiency. 

PMID- 25959674
TI  - Metabolism links bacterial biofilms and colon carcinogenesis.
AB  - Bacterial biofilms in the colon alter the host tissue microenvironment. A role
      for biofilms in colon cancer metabolism has been suggested but to date has not
      been evaluated. Using metabolomics, we investigated the metabolic influence that
      microbial biofilms have on colon tissues and the related occurrence of cancer.
      Patient-matched colon cancers and histologically normal tissues, with or without
      biofilms, were examined. We show the upregulation of polyamine metabolites in
      tissues from cancer hosts with significant enhancement of N(1), N(12)
      diacetylspermine in both biofilm-positive cancer and normal tissues. Antibiotic
      treatment, which cleared biofilms, decreased N(1), N(12)-diacetylspermine levels
      to those seen in biofilm-negative tissues, indicating that host cancer and
      bacterial biofilm structures contribute to the polyamine metabolite pool. These
      results show that colonic mucosal biofilms alter the cancer metabolome to produce
      a regulator of cellular proliferation and colon cancer growth potentially
      affecting cancer development and progression. 

PMID- 25959675
TI  - Nitrogen excretion factors of livestock in the European Union: a review.
AB  - Livestock manures are major sources of nutrients, used for the fertilisation of
      cropland and grassland. Accurate estimates of the amounts of nutrients in
      livestock manures are required for nutrient management planning, but also for
      estimating nitrogen (N) budgets and emissions to the environment. Here we report
      on N excretion factors for a range of animal categories in policy reports by
      member states of the European Union (EU). Nitrogen excretion is defined in this
      paper as the total amount of N excreted by livestock per year as urine and
      faeces. We discuss the guidelines and methodologies for the estimation of N
      excretion factors by the EU Nitrates Directive, the OECD/Eurostat gross N balance
      guidebook, the EMEP/EEA Guidebook and the IPCC Guidelines. Our results show that
      N excretion factors for dairy cattle, other cattle, pigs, laying hens, broilers,
      sheep, and goats differ significantly between policy reports and between
      countries. Part of these differences may be related to differences in animal
      production (e.g. production of meat, milk and eggs), size/weight of the animals,
      and feed composition, but partly also to differences in the aggregation of
      livestock categories and estimation procedures. The methodologies and data used
      by member states are often not well described. There is a need for a common,
      harmonised methodology and procedure for the estimation of N excretion factors,
      to arrive at a common basis for the estimation of the production of manure N and
      N balances, and emissions of ammonia (NH3 ) and nitrous oxide (N2 O) across the
      EU.

PMID- 25959676
TI  - Delayed enrichment for c-kit and inducing cardiac differentiation attenuated
      protective effects of BMSCs' transplantation in pig model of acute myocardial
      ischemia.
AB  - OBJECTIVE: To investigate the effects of immature cardiomyocytes differentiated
      from c-kit(+) bone marrow mesenchymal stem cells (BMSCs) against acute myocardial
      infarction (AMI). METHODS: Miniswine passage 8 BMSCs were enriched for c-kit and
      induced by 5 MUM 5-azacytidine (AZA) for 14 days, and a second enrichment for the
      dihydropyridine receptor subunit alpha2delta1 was performed (enriched BMSCs).
      Thereafter, enriched BMSCs were analyzed by determining cardiac differentiation,
      secretion function, and the effects of these secreted factors on cardiac stem
      cells (CSCs). Miniswine with AMI were divided into control, primary BMSCs' (PB),
      and enriched BMSCs' (EB) groups. Autologous BMSCs were intramyocardially injected
      into the ischemic regions in PB and EB groups. The following indices were
      evaluated at different time points, including paracrine of implanted BMSCs,
      histological and morphological analysis, myocardial perfusion, and cardiac
      function. RESULTS: As shown by in vitro study, enrichment + AZA significantly
      promoted BMSCs to express cardiac-specific markers and format action potential,
      but down-regulated the expression of VEGF and bFGF, consequently attenuated BMSCs
      inducing CSCs proliferation, migration, and differentiation. The in vivo
      experiments revealed similar results like the in vitro 6 weeks postoperatively.
      And in EB group, there were decreased angiogenesis and myocardial perfusion,
      attenuated resident CSCs-mediated myocardial regeneration, and consequently
      impaired cardiac function compared with PB group. CONCLUSIONS: This pretreatment
      promoted BMSCs to differentiate into myocardiocytes both in vitro and in vivo,
      but impaired their paracrine function and effects on resident CSCs, suggesting
      that inducing cardiac differentiation alone may not improve protective effects of
      BMSCs transplantation on AMI.

PMID- 25959677
TI  - A Study of the Interaction between a Family of Gemini Amphiphilic Pseudopeptides
      and Model Monomolecular Film Membranes Formed with a Cardiolipin.
AB  - The interaction between five gemini amphiphilic pseudopeptides (GAPs) differing
      by the length of the central spacer and a model membrane lipid, 1,3-bis[1,2
      dimyristoyl-sn-glycero-3-phospho]-sn-glycerol (cardiolipin) were studied with the
      aim to evaluate their possible antimicrobial properties. To this end,
      monomolecular films were formed at the air/water interface with pure cardiolipin
      or cardiolipin/GAPs mixtures; film properties were determined using surface
      pressure and surface potential measurements, as well as polarization-modulation
      infrared reflection-absorption spectroscopy. Moreover, to better understand the
      GAPs-phospholipid interaction at the molecular level, molecular dynamics
      simulations were performed. The results obtained indicate that the length of the
      central spacer has an effect on the interaction of GAPs with cardiolipin and on
      the properties of the lipid film. The GAPs with the longer linkers can be
      expected to be useful for biological membrane modification and for possible
      antimicrobial applications. 

PMID- 25959678
TI  - Autophagosome-lysosome fusion is independent of V-ATPase-mediated acidification.
AB  - The ATP-dependent proton pump V-ATPase ensures low intralysosomal pH, which is
      essential for lysosomal hydrolase activity. Based on studies with the V-ATPase
      inhibitor BafilomycinA1, lysosomal acidification is also thought to be required
      for fusion with incoming vesicles from the autophagic and endocytic pathways.
      Here we show that loss of V-ATPase subunits in the Drosophila fat body causes an
      accumulation of non-functional lysosomes, leading to a block in autophagic flux.
      However, V-ATPase-deficient lysosomes remain competent to fuse with
      autophagosomes and endosomes, resulting in a time-dependent formation of giant
      autolysosomes. In contrast, BafilomycinA1 prevents autophagosome-lysosome fusion
      in these cells, and this defect is phenocopied by depletion of the Ca(2+) pump
      SERCA, a secondary target of this drug. Moreover, activation of SERCA promotes
      fusion in a BafilomycinA1-sensitive manner. Collectively, our results indicate
      that lysosomal acidification is not a prerequisite for fusion, and that
      BafilomycinA1 inhibits fusion independent of its effect on lysosomal pH. 

PMID- 25959681
TI  - Simple metal under tensile stress: layer-dependent herringbone reconstruction of
      thin potassium films on graphite.
AB  - While understanding the properties of materials under stress is fundamentally
      important, designing experiments to probe the effects of large tensile stress is
      difficult. Here tensile stress is created in thin films of potassium (up to 4
      atomic layers) by epitaxial growth on a rigid support, graphite. We find that
      this "simple" metal shows a long-range, periodic "herringbone" reconstruction,
      observed in 2- and 3- (but not 1- and 4-) layer films by low-temperature scanning
      tunneling microscopy (STM). Such a pattern has never been observed in a simple
      metal. Density functional theory (DFT)simulations indicate that the
      reconstruction consists of self-aligned stripes of enhanced atom density formed
      to relieve the tensile strain. At the same time marked layer-dependent charging
      effects lead to substantial variation in the apparent STM layer heights. 

PMID- 25959680
TI  - The prognostic value of perioperative profiles of ACTH and cortisol for
      recurrence after transsphenoidal hypophysectomy in dogs with corticotroph
      adenomas.
AB  - BACKGROUND: Transsphenoidal hypophysectomy is an effective treatment for dogs
      with pituitary-dependent hypercortisolism (PDH). However, long-term recurrence of
      hypercortisolism is a well-recognized problem, indicating the need for reliable
      prognostic indicators. OBJECTIVES: The aim of this study was to evaluate the
      prognostic value of perioperative plasma ACTH and cortisol concentrations for
      identifying recurrence of hypercortisolism after transsphenoidal hypophysectomy.
      ANIMALS: A total of 112 dogs with PDH that underwent transsphenoidal
      hypophysectomy met the inclusion criteria of the study. METHODS: Hormone
      concentrations were measured preoperatively and 1-5 hours after surgery. Both
      absolute hormone concentrations and postoperative concentrations normalized to
      preoperative concentrations were included in analyses. The prognostic value of
      hormone concentrations was studied with Cox's proportional hazard analysis.
      RESULTS: Median follow-up and disease-free period were 1096 days and 896 days,
      respectively. Twenty-eight percent of patients had recurrence, with a median
      disease-free period of 588 days. Both absolute and normalized postoperative
      cortisol concentrations were significantly higher in dogs with recurrence than in
      dogs without recurrence. High ACTH 5 hours after surgery, high cortisol 1 and 4
      hours after surgery, high normalized ACTH 3 hours after surgery, high normalized
      cortisol 4 hours after surgery and the random slope of cortisol were associated
      with a shorter disease-free period. CONCLUSIONS AND CLINICAL IMPORTANCE:
      Individual perioperative hormone curves provide valuable information about the
      risk of recurrence after hypophysectomy. However, because no single cutoff point
      could be identified, combination with other variables, such as the pituitary
      height/brain area (P/B) ratio, is still needed to obtain a good estimate of the
      risk for recurrence of hypercortisolism after hypophysectomy.

PMID- 25959679
TI  - High Emergency Lung Transplantation: dramatic decrease of waiting list death rate
      without relevant higher post-transplant mortality.
AB  - Many candidates for lung transplantation (LT) die on the waiting list, raising
      the question of graft availability and strategy for organ allocation. We report
      the experience of the new organ allocation program, "High Emergency Lung
      Transplantation" (HELT), since its implementation in our center in 2007.
      Retrospective analysis of 201 lung transplant patients, of whom 37 received HELT
      from 1st July 2007 to 31th May 2012. HELT candidates had a higher impairment
      grade on respiratory status and higher Lung Allocation Score (LAS). HELT patients
      had increased incidence of perioperative complications (e.g., perioperative
      bleeding) and extracorporeal circulatory assistance (75% vs. 36.6%, P = 0.0005).
      No significant difference was observed between HELT and non-HELT patients in
      mechanical ventilation duration (15.5 days vs. 11 days, P = 0.27), intensive care
      unit length of stay (15 days vs. 10 days, P = 0.22) or survival rate at 12 (81%
      vs. 80%), and 24 months post-LT (72.9% vs. 75.0%). Lastly, mortality on the
      waiting list was spectacularly reduced from 19% to 2% when compared to the non
      HELT 2004-2007 group. Despite a more severe clinical status of patients on the
      waiting list, HELT provided similar results to conventional LT. These results
      were associated with a dramatic reduction in the mortality rate of patients on
      the waiting list. 

PMID- 25959682
TI  - The trajectory of disturbed resting-state cerebral function in Parkinson's
      disease at different Hoehn and Yahr stages.
AB  - OBJECTIVE: We aim to investigate the disturbance of neural network associated
      with the different clinical stages of Parkinson's disease (PD). METHOD: We
      recruited 80 patients at different H&Y stages of PD (28 at H&Y stage I, 28 at H&Y
      stage II, 24 at H&Y stage III) and 30 normal controls. All participants underwent
      resting-state fMRI scans on a 3-T MR system. The amplitude of low-frequency
      fluctuation (ALFF) of blood oxygen level-dependent signals was used to
      characterize regional cerebral function. Functional integration across the brain
      regions was evaluated by a seed voxel correlation approach. RESULTS: PD patients
      had decreased regional activities in left occipital and lingual regions; these
      regions show decreased functional connection pattern with temporal regions, which
      is deteriorating as H&Y stage ascending. In addition, PD patients, especially
      those at stage II, exhibit increased regional activity in the posterior regions
      of default mode network (DMN), increased anticorrelation between posterior
      cingulate cortex (PCC) and cortical regions outside DMN, and higher temporal
      coherence within DMN. Those indicate more highly functioned DMN in PD patients at
      stage II. CONCLUSIONS: Our study demonstrated the trajectories of resting-state
      cerebral function disturbance in PD patients at different H&Y stages. Impairment
      in functional integration of occipital-temporal cortex might be a promising
      measurement to evaluate and potentially track functional substrates of disease
      evolution of PD.

PMID- 25959683
TI  - Elucidation of IgH 3' region regulatory role during class switch recombination
      via germline deletion.
AB  - In mature B cells, class switch recombination (CSR) replaces the expressed
      constant CMU gene with a downstream C(H) gene. How the four transcriptional
      enhancers of the IgH 3' regulatory region (3'RR) control CSR remains an open
      question. We have investigated IgG1 CSR in 3'RR-deficient mice. Here we show that
      the 3'RR enhancers target the S(gamma1) acceptor region (and poorly the S(MU)
      donor region) by acting on epigenetic marks, germline transcription, paused RNA
      Pol II recruitment, R loop formation, AID targeting and double-strand break
      generation. In contrast, location and diversity of S(MU)-S(gamma1) junctions are
      not affected by deletion of the 3'RR enhancers. Thus, the 3'RR controls the first
      steps of CSR by priming the S acceptor region but is not implicated in the choice
      of the end-joining pathway.

PMID- 25959684
TI  - Four different synthetic peptides of proteolipid protein induce a distinct
      antibody response in MP4-induced experimental autoimmune encephalomyelitis.
AB  - Here we studied the autoantibody specificity elicited by proteolipid protein
      (PLP) in MP4-induced experimental autoimmune encephalomyelitis, a mouse model of
      multiple sclerosis (MS). In C57BL/6 (B6) mice, antibodies were induced by
      immunization with one of the two extracellular and by the intracellular PLP
      domain. Antibodies against extracellular PLP were myelin-reactive in
      oligodendrocyte cultures and induced mild spinal cord demyelination upon transfer
      into B cell-deficient J(H)T mice. Remarkably, also antibodies against
      intracellular PLP showed binding to intact oligodendrocytes and were capable of
      inducing myelin pathology upon transfer into J(H)T mice. In MP4-immunized mice
      peptide-specific T(H)1/T(H)17 responses were mainly directed against the
      extracellular PLP domains, but also involved the intracellular epitopes. These
      data suggest that both extracellular and intracellular epitopes of PLP contribute
      to the pathogenesis of MP4-induced EAE already in the setting of intact myelin.
      It remains to be elucidated if this concept also applies to MS itself.

PMID- 25959685
TI  - Theranostic nanoemulsions for macrophage COX-2 inhibition in a murine
      inflammation model.
AB  - Targeting macrophages for therapeutic and diagnostic purposes is an attractive
      approach applicable to multiple diseases. Here, we present a theranostic
      nanoemulsion platform for simultaneous delivery of an anti-inflammatory drug
      (celecoxib) to macrophages and monitoring of macrophage migration patterns by
      optical imaging, as measurement of changes in inflammation. The anti-inflammatory
      effect of the theranostic nanoemulsions was evaluated in a mouse inflammation
      model induced with complete Freund's adjuvant (CFA). Nanoemulsions showed greater
      accumulation in the inflamed vs. control paw, with histology confirming their
      specific localization in CD68 positive macrophages expressing cyclooxygenase-2
      (COX-2) compared to neutrophils. With a single dose administration of the
      celecoxib-loaded theranostic, we observed a reduction in fluorescence in the paw
      with time, corresponding to a reduction in macrophage infiltration. Our data
      strongly suggest that delivery of select agents to infiltrating macrophages can
      potentially lead to new treatments of inflammatory diseases where macrophage
      behavior changes are monitored in vivo. 

PMID- 25959687
TI  - A fast track for exceptional research.

PMID- 25959688
TI  - Examining extrinsic factors that influence product acceptance: a review.
AB  - Drivers of liking (DOL) studies are useful for product development to formulate
      acceptable products; however, DOL alone are insufficient for understanding why a
      product is purchased and repurchased, which is ultimately the indication of a
      successful product. Ultimately sensory attributes drive product success (that is,
      repeat and continued purchase). However, ignoring the importance of extrinsic
      factors may neglect the vital product attributes responsible for the initial
      purchase, which may in turn, affect repeat purchase. The perception of sensory
      attributes assessed by DOL is mitigated by external perceptions of quality. If
      the sensory attributes do not deliver based upon the quality cues, the product
      will not be acceptable. Four key extrinsic factors that affect DOL are the
      perceived satiety, brand and labeling, price, and the emotional impact to
      decision making. In order to more thoroughly understand what the DOL for a
      product is, these 4 product cues should be considered in conjunction with sensory
      attribute perception to gain a holistic understanding of product acceptance. 

PMID- 25959690
TI  - Journal of Bone and Mineral Research: Volume 30, Issue 5, May 2015, Frontmatter
      page ii.

PMID- 25959691
TI  - Molecular characterisation of Cryptosporidium and Giardia in cats (Felis catus)
      in Western Australia.
AB  - Little is known of the prevalence of Cryptosporidium and Giardia in domestic cats
      in Western Australia and their potential role as zoonotic reservoirs for human
      infection. In the present study, a total of 345 faecal samples from four
      different sources were screened for the presence of Cryptosporidium and Giardia
      by PCR and genotyped by sequence analysis. Oocyst numbers and cyst numbers for
      Cryptosporidium and Giardia respectively were also determined using quantitative
      PCR assays. Cryptosporidium and Giardia were detected in 9.9% (95% CI 6.7-13.0)
      and 10.1% (95% CI 7.0-13.3) of cats in Western Australia respectively. Sequence
      analysis at the 18S rRNA locus identified five Cryptosporidium species/genotypes;
      C. felis (n = 8), C. muris (n = 1), C. ryanae (n = 1), Cryptosporidium rat
      genotype III (n = 5) and a novel genotype most closely related to Cryptosporidium
      rat genotype III in one isolate. This is the first report of C. ryanae and
      Cryptosporidium rat genotype III in cats. For Giardia, assemblage F the most
      commonly identified species, while only 1 assemblage sequence was detected. Since
      most human cases of cryptosporidiosis are caused by C. parvum and C. hominis and
      human cases of giardiasis are caused by G. duodenalis assemblage A and B, the
      domestic cats in the present study are likely to be of low zoonotic risk to pet
      owners in Perth. Risk analyses identified that elderly cats (more than 6 years)
      were more prone to Cryptosporidium and Giardia infections than kittens (less than
      6 months) (P = 0.009). Clinical symptoms were not associated with the prevalence
      of Cryptosporidium and Giardia infections in cats.

PMID- 25959693
TI  - Geographic distribution and adaptive significance of genomic structural variants:
      an anthropological genetics perspective.
AB  - Anthropological geneticists have successfully used single-nucleotide and short
      tandem repeat variations across human genomes to reconstruct human history. These
      markers have also been used extensively to identify adaptive and phenotypic
      variation. The recent advent of high-throughput genomic technologies revealed an
      overlooked type of genomic variation: structural variants (SVs). In fact, some
      SVs may contribute to human adaptation in substantial and previously unexplored
      ways. SVs include deletions, insertions, duplications, inversions, and
      translocations of genomic segments that vary among individuals from the same
      species. SVs are much less numerous than single-nucleotide variants but account
      for at least seven times more variable base pairs than do single-nucleotide
      variants when two human genomes are compared. Moreover, recent studies have shown
      that SVs have higher mutation rates than single-nucleotide variants when the
      affected base pairs are considered, especially in certain parts of the genome.
      The null hypothesis for the evolution of SVs, as for single-nucleotide variants,
      is neutrality. Hence, drift is the primary force that shapes the current allelic
      distribution of most SVs. However, due to their size, a larger proportion of SVs
      appear to evolve under nonneutral forces (mostly purifying selection) than do
      single-nucleotide variants. In fact, as exemplified by several groundbreaking
      studies, SVs contribute to anthropologically relevant phenotypic variation and
      local adaptation among humans. In this review, we argue that with the advent of
      affordable genomic technologies, anthropological scrutiny of genomic structural
      variation emerges as a fertile area of inquiry to better understand human
      phenotypic variation. To motivate potential studies, we discuss scenarios through
      which structural variants (SVs) affect phenotypic variation among humans within
      an anthropological context. We further provide a methodological workflow in which
      we analyzed 1000 Genomes deletion variants and identified 16 exonic deletions
      that are specific to the African continent. We analyzed two of these deletion
      variants affecting the keratin-associated protein (KAP) cluster in a locus
      specific manner. Our analysis revealed that these deletions may indeed affect
      phenotype and likely evolved under geography-specific positive selection. We
      outline all the major software and data sets for these analyses and provide the
      basic R and Perl codes we used for this example workflow analysis. Overall, we
      hope that this review will encourage and facilitate incorporation of genomic
      structural variation in anthropological research programs.

PMID- 25959692
TI  - A mitochondrial haplogroup is associated with decreased longevity in a historic
      new world population.
AB  - Interest in mitochondrial influences on extended longevity has been mounting, as
      evidenced by a growing literature. Such work has demonstrated that some
      haplogroups are associated with increased longevity and that such associations
      are population specific. Most previous work, however, suffers from the
      methodological shortcoming that long-lived individuals are compared with
      "controls" who are born decades after the aged individuals. The only true
      controls of the elderly are people who were born in the same time period but who
      did not have extended longevity. Here we present results of a study in which we
      are able to test whether longevity is independent of haplogroup type, controlling
      for time period, by using mtDNA genealogies. Since mtDNA does not recombine, we
      know the mtDNA haplogroup of the maternal ancestors of our living participants.
      Thus, we can compare the haplogroup of people with and without extended longevity
      who were born during the same time period. Our sample is an admixed New World
      population that has haplogroups of Amerindian, European, and African origin. We
      show that women who belong to Amerindian, European, and African haplogroups do
      not differ in their mean longevity. Therefore, to the extent that ethnicity was
      tied in this population to mtDNA make-up, such ethnicity did not impact
      longevity. In support of previous suggestions that the link between mtDNA
      haplogroups and longevity is specific to the population being studied, we found
      an association between haplogroup C and decreased longevity. Interestingly, the
      lifetime reproductive success and the number of grandchildren produced via a
      daughter of women with haplogroup C are not reduced. Our diachronic approach to
      the mtDNA and longevity link allowed us to determine that the same haplogroup is
      associated with decreased longevity during different time periods and allowed us
      to compare the haplogroup of short- and long-lived individuals born during the
      same time period. By controlling for time period, we minimized the effect of
      different cultural and ecological environments on differential longevity. With
      our diachronic approach, we investigated the mtDNA and longevity link with a
      biocultural perspective. 

PMID- 25959694
TI  - Estimation of inbreeding and substructure levels in African-derived Brazilian
      quilombo populations.
AB  - This article deals with the estimation of inbreeding and substructure levels in a
      set of 10 (later regrouped as eight) African-derived quilombo communities from
      the Ribeira River Valley in the southern portion of the state of Sao Paulo,
      Brazil. Inbreeding levels were assessed through F-values estimated from the
      direct analysis of genealogical data and from the statistical analysis of a large
      set of 30 molecular markers. The levels of population substructure found were
      modest, as was the degree of inbreeding: in the set of all communities considered
      together, F-values were 0.00136 and 0.00248 when using raw and corrected data
      from their complete genealogical structures, respectively, and 0.022 and 0.036
      when using the information taken from the statistical analysis of all 30 loci and
      of 14 single-nucleotide polymorphic loci, respectively. The overall frequency of
      consanguineous marriages in the set of all communities considered together was ~
      2%. Although modest, the values of the estimated parameters are much larger than
      those obtained for the overall Brazilian population and in general much smaller
      than the ones recorded for other Brazilian isolates. To circumvent problems
      related to heterogeneous sampling and virtual absence of reliable records of
      biological relationships, we had to develop or adapt several methods for making
      valid estimates of the prescribed parameters.

PMID- 25959695
TI  - Genetic analysis of 17 Y-STRs in a Mestizo population from the Central Valley of
      Mexico.
AB  - This study aims to portray the complex diversity of the Mexican Mestizo
      population, which represents 98.8% of the entire population of Mexico. We
      compiled extended haplotype data of the Y chromosome from populations in the
      Central Valley of Mexico (CVM), which we compared with other Mestizo and parental
      (Amerindian, European, and African) populations. A complex ancestral relationship
      was found in the CVM population, suggesting cosmopolitan origins. Nevertheless,
      the most preeminent lineages point toward a European ancestry, where the R1b
      lineage was most frequent. In addition, important frequencies of Amerindian
      lineages were also found in the Mestizo sample studied. Interestingly, the
      Amerindian ancestry showed a remarkable substructure, which was represented by
      the two main founding lineages: QL54 (* M3) and M3. However, even within each
      lineage a high diversity was found despite the small number of sample bearers of
      these lineages. Further, we detected important genetic differences between the
      CVM populations and the Mexican Mestizo populations from the north and south.
      This result points to the fact that Mestizo populations present different
      ancestral proportions, which are related to the demographic events that gave
      origin to each population. Finally, we provide additional forensic statistical
      parameters that are useful in the interpretation of genetic analysis where
      autosomal loci are limited. Our findings illustrate the complex genetic
      background of the Mexican Mestizo population and reinforce the need to encompass
      more geographic regions to generate more robust data for forensic applications. 

PMID- 25959696
TI  - How much DNA is lost? Measuring DNA loss of short-tandem-repeat length fragments
      targeted by the PowerPlex 16(r) system using the Qiagen MinElute Purification
      Kit.
AB  - The success in recovering genetic profiles from aged and degraded biological
      samples is diminished by fundamental aspects of DNA extraction, as well as its
      long-term preservation, that are not well understood. While numerous studies have
      been conducted to determine whether one extraction method was superior to others,
      nearly all of them were initiated with no knowledge of the actual starting DNA
      quantity in the samples prior to extraction, so they ultimately compared the
      outcome of all methods relative to the best. Using quantitative PCR to estimate
      the copy count of synthetic standards before (i.e., "copies in") and after (i.e.,
      "copies out") purification by the Qiagen MinElute PCR Purification Kit, we
      documented DNA loss within a pool of 16 different-sized fragments ranging from
      106 to 409 bp in length, corresponding to those targeted by the PowerPlex 16
      System (Promega, Madison, WI). Across all standards from 10(4) to 10(7)
      copies/MUL, loss averaged between 21.75% and 60.56% (mean, 39.03%), which is not
      congruent with Qiagen's claim that 80% of 70 bp to 4 kb fragments are retained
      using this product (i.e., 20% loss). Our study also found no clear relationship
      either between DNA strand length and retention or between starting copy number
      and retention. This suggests that there is no molecule bias across the MinElute
      column membrane and highlights the need for manufacturers to clearly and
      accurately describe on what their claims are based, and should also encourage
      researchers to document DNA retention efficiencies of their own methods and
      protocols. Understanding how and where to reduce loss of molecules during
      extraction and purification will serve to generate clearer and more accurate
      data, which will enhance the utility of ancient and low-copy-number DNA as a tool
      for closing forensic cases or in reconstructing the evolutionary history of
      humans and other organisms. 

PMID- 25959698
TI  - Characteristics of Left Atrial Deformation Parameters and Their Prognostic Impact
      in Patients with Pathological Left Ventricular Hypertrophy: Analysis by Speckle
      Tracking Echocardiography.
AB  - BACKGROUND: The pathological process of left ventricular (LV) hypertrophy is
      associated with left atrial (LA) remodeling. This study was aimed to evaluate the
      prognostic value of LA strain parameters in patients with pathological LV
      hypertrophy. METHODS: This study included 95 patients with hypertensive heart
      disease (HHD: n = 24), hypertrophic cardiomyopathy (HCM: n = 56), cardiac
      amyloidosis (CA: n = 15), and control subjects (n = 20). We used two-dimensional
      speckle tracking echocardiography (STE) to analyze LA global strain. LA
      electromechanical conduction time (EMT) at the septal (EMT-septal) and lateral
      wall (EMT-lateral), and their time difference (EMT-diff) were calculated. The
      incidence of cardiac death and heart failure hospitalization was defined as major
      cardiac events and that of atrial fibrillation as secondary outcome. RESULTS:
      Left atrial volume index was increased and LA booster strain was decreased in the
      HCM and CA groups compared with the HHD group. EMT-lateral was increased in the
      diseased groups compared with the control. EMT-diff was prolonged in the CA group
      compared with the HCM group. During the follow-up period (mean 3.4 years), major
      cardiac events and atrial fibrillation occurred in 17 and 13 patients,
      respectively. The occurrence of atrial fibrillation was associated with CA
      etiology, E/e', LA volume index, LAa, and EMT-lateral. The incidence of major
      cardiac events was independently correlated with LA volume index and EMT-diff in
      multivariate analysis. CONCLUSION: This study suggested that the EMT-diff could
      discriminate patients with a high risk of cardiac events among patients with
      pathological LV hypertrophy.

PMID- 25959699
TI  - Case of malignant melanoma developing from the dermal component of a small
      intradermal nevus.

PMID- 25959700
TI  - Ozone exposure and systemic biomarkers: Evaluation of evidence for adverse
      cardiovascular health impacts.
AB  - The US Environmental Protection Agency (EPA) recently concluded that there is
      likely to be a causal relationship between short-term (< 30 days) ozone exposure
      and cardiovascular (CV) effects; however, biological mechanisms to link transient
      effects with chronic cardiovascular disease (CVD) have not been established. Some
      studies assessed changes in circulating levels of biomarkers associated with
      inflammation, oxidative stress, coagulation, vasoreactivity, lipidology, and
      glucose metabolism after ozone exposure to elucidate a biological mechanism. We
      conducted a weight-of-evidence (WoE) analysis to determine if there is evidence
      supporting an association between changes in these biomarkers and short-term
      ozone exposure that would indicate a biological mechanism for CVD below the ozone
      National Ambient Air Quality Standard (NAAQS) of 75 parts per billion (ppb).
      Epidemiology findings were mixed for all biomarker categories, with only a few
      studies reporting statistically significant changes and with no consistency in
      the direction of the reported effects. Controlled human exposure studies of 2 to
      5 hours conducted at ozone concentrations above 75 ppb reported small elevations
      in biomarkers for inflammation and oxidative stress that were of uncertain
      clinical relevance. Experimental animal studies reported more consistent results
      among certain biomarkers, although these were also conducted at ozone exposures
      well above 75 ppb and provided limited information on ozone exposure-response
      relationships. Overall, the current WoE does not provide a convincing case for a
      causal relationship between short-term ozone exposure below the NAAQS and adverse
      changes in levels of biomarkers within and across categories, but, because of
      study limitations, they cannot not provide definitive evidence of a lack of
      causation. 

PMID- 25959701
TI  - New Interview and Observation Measures of the Broader Autism Phenotype:
      Description of Strategy and Reliability Findings for the Interview Measures.
AB  - Clinical genetic studies confirm the broader autism phenotype (BAP) in some
      relatives of individuals with autism, but there are few standardized assessment
      measures. We developed three BAP measures (informant interview, self-report
      interview, and impression of interviewee observational scale) and describe the
      development strategy and findings from the interviews. International Molecular
      Genetic Study of Autism Consortium data were collected from families containing
      at least two individuals with autism. Comparison of the informant and self-report
      interviews was restricted to samples in which the interviews were undertaken by
      different researchers from that site (251 UK informants, 119 from the
      Netherlands). Researchers produced vignettes that were rated blind by others.
      Retest reliability was assessed in 45 participants. Agreement between live
      scoring and vignette ratings was very high. Retest stability for the interviews
      was high. Factor analysis indicated a first factor comprising social
      communication items and rigidity (but not other repetitive domain items), and a
      second factor comprised mainly of reading and spelling impairments. Whole scale
      Cronbach's alphas were high for both interviews. The correlation between
      interviews for factor 1 was moderate (adult items 0.50; childhood items 0.43);
      Kappa values for between-interview agreement on individual items were mainly low.
      The correlations between individual items and total score were moderate. The
      inclusion of several factor 2 items lowered the overall Cronbach's alpha for the
      total set. Both interview measures showed good reliability and substantial
      stability over time, but the findings were better for factor 1 than factor 2. We
      recommend factor 1 scores be used for characterising the BAP.

PMID- 25959703
TI  - Broad spectrum psychiatric comorbidity is associated with better executive
      functioning in an inpatient sample of individuals with schizophrenia.
AB  - BACKGROUND: Individuals with schizophrenia exhibit cognitive deficits but whether
      these deficits are exacerbated by broad spectrum psychiatric comorbidity (i.e.,
      comorbidity that is inclusive of disorders from different diagnostic categories)
      is unclear. A broad spectrum approach to psychiatric comorbidity is an
      ecologically valid way to capture the diagnostic heterogeneity inherent in
      psychiatric presentations. OBJECTIVE: This study compared the attention, working
      memory, processing speed, and executive functioning of individuals with
      schizophrenia only relative to individuals with schizophrenia and broad spectrum
      psychiatric comorbidity. METHOD: Archival patient neuropsychological test data
      were obtained for a sample of patients with schizophrenia only (n=30) and a
      sample of patients with schizophrenia and psychiatric comorbidity (n=33).
      Relevant tests were used to form composite indices for the cognitive domains of
      attention, working memory, speed of processing, and executive functioning.
      RESULTS: Unexpectedly, individuals with schizophrenia and psychiatric comorbidity
      had significantly better executive functioning than individuals with
      schizophrenia only. There were no other significant differences. CONCLUSIONS: A
      broad spectrum approach to psychiatric comorbidity can help to account for
      differences in the executive functioning of individuals with schizophrenia. In
      clinical settings, individuals with schizophrenia and psychiatric comorbidity may
      benefit from intervention strategies that capitalize on their relatively higher
      executive functioning.

PMID- 25959704
TI  - Knowledge and competence with patient safety as perceived by nursing students:
      The findings of a cross-sectional study.
AB  - BACKGROUND: Ensuring safety in health-care settings is provoking improvements
      both in education and clinical practice. However, the studies available have not
      offered to date information regarding knowledge and competence on patient safety
      (PS) developed by nursing students over their academic career. There is no
      documentation of the amount of close calls and/or adverse events that students
      may have witnessed and the degree of safety perceived in the attended clinical
      settings. OBJECTIVES: To describe the perception of nursing students regarding
      their own knowledge and competence on PS and describe differences, if any, among
      students attending the first, second and third academic year. DESIGN: A cross
      sectional study design was undertaken in 2013. PARTICIPANTS AND SETTING: A
      convenience sample of 621 nursing students of two bachelors nursing degrees
      located in two Italian universities, was the population target of the study.
      Students attending the first, second and third academic year, obtaining admission
      to the annual clinical competence examination, were eligible. METHODS: The
      Italian version of the Health Professional Education in Patient Safety Survey (H
      PEPSSIta) and open-ended questions was administered to the students after having
      obtained their informed written consent. RESULTS: A total of 573 students
      (response rate 92.4%) participated. Around a quarter (28.8%) of students reported
      having experienced an adverse event or close call during their clinical
      experience. The settings where they learn were perceived as unsafe by 46.9% of
      students. PS knowledge and competence as perceived by students, was high
      (Median=4) in all factors and dimensions of the H-PEPSSIta tool. High PS
      knowledge and competence was reported by first-year students, moderate by second
      year students and higher at the end of the third-year. CONCLUSIONS: Faculties and
      health-care institutions offering clinical placements have to share the
      responsibility of well-prepared future nurses, working together to improve PS
      through dialogue when issues are identified by students.

PMID- 25959705
TI  - Role of the ubiquitin-proteasome system and autophagy in regulation of insulin
      sensitivity in serum-starved 3T3-L1 adipocytes.
AB  - The ubiquitin-proteasome system (UPS) and autophagy are two conserved
      intracellular proteolytic pathways, responsible for degradation of most cellular
      proteins in living cells. Currently, both the UPS and autophagy have been
      suggested to be associated with pathogenesis of insulin resistance and diabetes.
      However, underlying mechanism remains largely unknown. The purpose of the present
      study is to investigate the impact of the UPS and autophagy on insulin
      sensitivity in serum-starved 3T3-L1 adipocytes. Our results show that serum
      depletion resulted in activation of the UPS and autophagy, accompanied with
      increased insulin sensitivity. Inhibition of the UPS with bortezomib (BZM), a
      highly selective, reversible 26S proteasome inhibitor induced compensatory
      activation of autophagy but did not affect significantly insulin action. Genetic
      and pharmacological inhibition of autophagy dramatically mitigated serum
      starvation-elevated insulin sensitivity. In addition, autophagy inhibition
      compromised UPS function and led to endoplasmic reticulum (ER) stress and
      unfolded protein response (UPR). Inability of the UPS by BMZ exacerbated
      autophagy inhibition-induced ER stress and UPR. These results suggest that
      protein quality control maintained by the UPS and autophagy is required for
      preserving insulin sensitivity. Importantly, adaptive activation of autophagy
      plays a critical role in serum starvation-induced insulin sensitization in 3T3-L1
      adipocytes. 

PMID- 25959707
TI  - Effect of Kinesio Taping on gastrocnemius activity and ankle range of movement
      during gait in healthy adults: A randomized controlled trial.
AB  - OBJECTIVE: To examine the effect of KT on gastrocnemius surface electromyography
      (SEMG) activity and ankle range of motion during walking in healthy subjects.
      DESIGN: Randomized controlled trial, with concealed allocation and assessor
      blinding. SETTING: University Biomechanics Laboratory. PARTICIPANTS: Thirty six
      healthy physiotherapy students were randomized to KT or control group. OUTCOME
      MEASURES: At baseline and immediately after 72 h with the tape in situ: amplitude
      of LG SEMG activity during the stance phase, duration of the LG activity, onset
      and offset times of LG activity, ankle plantar- and dorsiflexion peaks, and the
      cadence of gait. RESULTS: ANOVA revealed a significant time * intervention
      interaction effect across two variables: duration of LG activation, F(1, 33) =
      4.71, p = .037, eta = .015; and onset F(1, 33) = 7.92, p = .008, eta = .037. KT
      group showed significantly shorter duration of the LG activity as compared with
      control, and similar results were observed when comparing the onset of LG
      activation. No statistically significant differences between both groups were
      noted in the rest of the outcomes. CONCLUSION: KT does significantly shorten the
      duration of the LG activity during gait when applied 72 h in healthy adults.
      However, this result was not accompanied by a significant reduction in the
      amplitude of LG SEMG activity.

PMID- 25959706
TI  - Experience of living with an enterocutaneous fistula.
AB  - AIMS AND OBJECTIVES: The purpose of this study was to describe patients'
      experiences of living with an enterocutaneous fistula. BACKGROUND: An
      enterocutaneous fistula is a complex and serious illness that usually occurs as a
      complication from surgery or spontaneously as a result of an underlying disease.
      The illness is demanding both physically and mentally and causes substantial
      medical and nursing problems for the afflicted individual. DESIGN: A descriptive
      design with a qualitative approach. METHODS: In-depth interviews were performed
      with nine participants who had experiences of living with an enterocutaneous
      fistula. The analysis was conducted using descriptive phenomenology according to
      Giorgi. RESULTS: The essence of this study was that living with an
      enterocutaneous fistula is about handling an illness that causes several
      limitations in daily life and the following five themes emerged from the data:
      restrictions in daily life, approaches to illness, emotions, dependence and need
      of support. A constant fear of leakage from the fistula appliance, being
      dependent on intravenous fluids and being dependent on health care professionals
      caused isolation and social restriction. CONCLUSIONS: The participants had many
      strategies for handling their illness. By being well trained, engaged and having
      a positive and understanding approach, health care professionals can encourage
      hope, motivation and self-care. This can lead to decreased dependence and help
      the patient to better handle their illness. RELEVANCE TO CLINICAL PRACTICE: The
      competence of health care professionals is essential in the care of patients with
      an enterocutaneous fistula.

PMID- 25959708
TI  - Intubation Efficiency and Perceived Ease of Use of Video Laryngoscopy vs Direct
      Laryngoscopy While Wearing HazMat PPE: A Preliminary High-fidelity Mannequin
      Study.
AB  - INTRODUCTION: Management of contaminated patients in the decontamination corridor
      requires the use of hazardous material (HazMat) personal protective equipment
      (PPE). Previous studies have demonstrated that HazMat PPE may increase the
      difficulty of airway management. This study compared the efficiency of video
      laryngoscopy (VL) with traditional direct laryngoscopy (DL) during endotracheal
      intubation (ETI) while wearing HazMat PPE. METHODS: Post-graduate year (PGY) 1-3
      Emergency Medicine residents were randomized to VL or DL while wearing
      encapsulating PPE. Video laryngoscopy was performed using the GlideScope Cobalt
      AVL video laryngoscope. The primary outcome measure was time to successful ETI in
      a high-fidelity simulation mannequin. Three time points were utilized in the
      analysis: Time 0 (blade at lips), Time 1 (blade removed from lips after
      endotracheal tube placement), and Time 2 (bag valve mask [BVM] attached to
      endotracheal tube). Secondary outcome measures were perceived ease of use and
      feasibility of VL and DL ETI modalities. RESULTS: Twenty-one of 23 (91.3%)
      eligible residents participated. Mean time to ETI was 10.0 seconds (SD=5.3
      seconds) in the DL group and 7.8 seconds (SD=3.0 seconds) in the VL group
      (P=.081). Mean times from blade insertion until BVM attachment were 17.4 seconds
      (SD=6.0 seconds) and 15.6 seconds (SD=4.6 seconds), respectively (P=.30). There
      were no unsuccessful intubation attempts. Seventeen out of 20 participants
      (85.0%) perceived VL to be easier to use when performing ETI in PPE. Twelve out
      of 20 participants (60%) perceived DL to be more feasible in an actual HazMat
      scenario. CONCLUSION: The time to successful ETI was not significantly different
      between VL and DL. Video laryngoscopy had a greater perceived ease of use, but DL
      was perceived to be more feasible for use in actual HazMat situations. These
      findings suggest that both DL and VL are reasonable modalities for use in HazMat
      situations, and the choice of modality could be based on the clinical situation
      and provider experience.

PMID- 25959709
TI  - Monodisperse Emulsion Drop Microenvironments for Bacterial Biofilm Growth.
AB  - In this work, microfluidic technology is used to rapidly create hundreds of
      thousands of monodisperse double and triple emulsion drops that serve as 3D
      microenvironments for the containment and growth of bacterial biofilms. The size
      of these drops, with diameters from tens to hundreds of micrometers, makes them
      amenable to rapid manipulation and analysis. This is demonstrated by using
      microscopy to visualize cellular differentiation of Bacillus subtilis biofilm
      communities within each drop and the bacterial biofilm microstructure. Biofilm
      growth is explored upon specific interfaces in double and triple emulsions and
      upon negative and positive radii of curvature. Biofilm attachment of matrix and
      flagella mutants is studied as well as biofilms of Pseudomonas aeruginosa. This
      is the first demonstration of biofilms grown in microscale emulsion drops, which
      serve as both templates and containers for biofilm growth and attachment. These
      microenvironments have the potential to transform existing high-throughput
      screening methods for bacterial biofilms. 

PMID- 25959710
TI  - The supportive care needs of parents caring for a child with a rare disease: A
      scoping review.
AB  - BACKGROUND: Parents caring for a child with a rare disease report unmet needs,
      the origins of which are varied and complex. Few studies have systematically
      attempted to identify the supportive care needs of parents with a child with a
      rare disease comprehensively. We have used the widely accepted Supportive Care
      Needs Framework (SCNF) as the structure for this review. OBJECTIVE: The purpose
      of the current review was to identify the supportive care needs of parents with a
      child with a rare disease, irrespective of condition. METHODS: We conducted a
      scoping study review comprising 29 studies (1990-2014) to identify and examine
      the research literature related to the supportive care needs of parents, and to
      compare these needs with the seven domains outlined in the SCNF. RESULTS: Most
      common needs cited were social needs (72% of papers), followed by informational
      needs (65% of papers) and emotional needs (62% of papers), with the most common
      parental needs overall being information about their child's disease, emotional
      stress, guilt and uncertainty about their child's future health care needs,
      parents own caring responsibilities and the need for more general support.
      CONCLUSION: A paucity of studies exists that explore the supportive care needs of
      parents of a child with a rare disease. The SCNF only partially reflects the
      breadth and type of needs of these parents, and a preliminary revised framework
      has been suggested. Further research is required in this area, particularly
      empirical research to amend or confirm the suggested new framework.

PMID- 25959711
TI  - Letter to the Editor on Saito et al., "Cough variant asthma patients are more
      depressed and anxious than classic asthma patients.".

PMID- 25959712
TI  - Could caveolae be acting as warnings of mitochondrial ageing?
AB  - Ageing is a cellular process with many facets, some of which are currently
      undergoing a paradigm change. It is the case of "mitochondrial theory of ageing",
      which, interestingly, has been found lately to cross paths with another ageing
      dysfunctional process - intracellular signalling - in an unexpected point (or
      place) - caveolae. The latter represent membrane microdomains altered in
      senescent cells, scaffolded by proteins modified (posttranslational or as
      expression) with ageing. An important determinant of these alterations is
      oxidative stress, through increased production of reactive oxygen species that
      originate at mitochondrial site. Spanning from physical contact points, to shared
      structural proteins and similar function domains, caveolae and mitochondria might
      have more in common than originally thought. By reviewing recent data on
      oxidative stress impact on caveolae and caveolins, as well as possible
      interactions between caveolae and mitochondria, we propose a hypothesis for
      senescence-related involvement of caveolins.

PMID- 25959713
TI  - Editorial overview: Large-scale recording technology: Scaling up neuroscience.

PMID- 25959714
TI  - The P300 as a build-to-threshold variable (Commentary on Twomey et al.).

PMID- 25959702
TI  - Diversity of 1,213 hepatitis C virus NS3 protease sequences from a clinical
      virology laboratory database in Marseille university hospitals, southeastern
      France.
AB  - Infection with hepatitis C virus (HCV) represents a major public health concern
      worldwide. Recent therapeutic advances have been considerable, HCV genotype
      continuing to guide therapeutic management. Since 2008, HCV genotyping in our
      clinical microbiology laboratory at university hospitals of Marseille,
      Southeastern France, has been based on NS3 protease gene population sequencing,
      to allow concurrent HCV genotype and protease inhibitor (PI) genotypic resistance
      determinations. We aimed, first, to analyze the genetic diversity of HCV NS3
      protease obtained from blood samples collected between 2003 and 2013 from
      patients monitored at university hospitals of Marseille and detect possible
      atypical sequences; and, second, to identify NS3 protease amino acid patterns
      associated with decreased susceptibility to HCV PIs. A total of 1,213 HCV NS3
      protease sequences were available in our laboratory sequence database. We
      implemented a strategy based on bioinformatic tools to determine whether HCV
      sequences are representative of our local HCV genetic diversity, or divergent. In
      our 2003-2012 HCV NS3 protease sequence database, we delineated 32 clusters
      representative of the majority HCV genetic diversity, and 61 divergent sequences.
      Five of these divergent sequences showed less than 85% nucleotide identity with
      their top GenBank hit. In addition, among the 294 sequences obtained in 2013,
      three were divergent relative to these 32 previously delineated clusters.
      Finally, we detected both natural and on-treatment genotypic resistance to HCV
      NS3 PIs, including a substantial prevalence of Q80K substitutions associated with
      decreased susceptibility to simeprevir, a second generation PI.

PMID- 25959715
TI  - STS-1 promotes IFN-alpha induced autophagy by activating the JAK1-STAT1 signaling
      pathway in B cells.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the
      overexpression of IFN-alpha. IFN-alpha induces autophagy via the JAK1-STAT1
      signaling pathway, contributing to the pathogenesis of SLE. Recent studies
      reported that B cells from patients with SLE and NZB/W F1 mice had enhanced
      autophagy activity; however, the mechanism still remains unknown. Here, we show
      that the protein tyrosine phosphatase STS-1 (suppressor of T-cell receptor
      signaling 1) was significantly overexpressed in B cells from patients with SLE
      and MRL/lpr mice. Notably, STS-1 promoted IFN-alpha-induced autophagy in B cells
      by enhancing the JAK1-STAT1 signaling activation. STS-1 inhibited the
      phosphorylation of the E3 ubiquitin protein ligase c-cbl, and subsequently
      promoted IFN-alpha-induced phosphorylation of tyrosine kinase 2, leading to JAK1
      STAT1 signaling activation. Furthermore, STAT1 and JAK1 inhibitors blocked the
      IFN-alpha-induced autophagy promoted by STS-1, indicating that STS-1 promotes IFN
      alpha-induced autophagy via the JAK1-STAT1 signaling. Our results demonstrate the
      importance of STS-1 in regulating IFN-alpha-induced autophagy in B cells, and
      this could be used as a therapeutic approach to treat SLE. 

PMID- 25959718
TI  - Synthesis of unsymmetric tertiary amines via alcohol amination.
AB  - The first one-pot selective synthesis of unsymmetric tertiary amines is reported
      by the amination of two types of alcohols with primary amines via the development
      of a simple CuAlOx-HT catalyst and enables the synthesis of unsymmetric amines in
      a wide variety of primary amines and alcohols. 

PMID- 25959717
TI  - Biochemical and physiological processes associated with the differential ozone
      response in ozone-tolerant and sensitive soybean genotypes.
AB  - Biochemical and physiological traits of two soybean [Glycine max (L.) Merr.]
      genotypes differing in sensitivity to ozone (O3 ) were investigated to determine
      the possible basis for the differential response. Fiskeby III (O3 -tolerant) and
      Mandarin (Ottawa) (O3 -sensitive) were grown in a greenhouse with charcoal
      filtered air for 4 weeks, then treated with O3 for 7 h.day(-1) in greenhouse
      chambers. Mandarin (Ottawa) showed significantly more leaf injury and hydrogen
      peroxide (H2 O2 ) and superoxide (O2 (-) ) production compared with Fiskeby III.
      Peroxidase activity in Mandarin (Ottawa) was 31% higher with O3 but was not
      significantly different in Fiskeby III. Ozone did not affect superoxide dismutase
      or glutathione reductase activities, or leaf concentrations of glutathione or
      ascorbic acid. Thus, variation in O3 response between Fiskeby III and Mandarin
      (Ottawa) was not explained by differences in antioxidant enzymes and metabolites
      tested. Ethylene emission from leaves declined in Fiskeby III following O3
      exposure but not in Mandarin (Ottawa). Ozone exposure reduced quantum yield
      (PhiPSII ), electron transport rate (ETR) and photochemical quenching (qp ) in
      Mandarin (Ottawa) more than in Fiskeby III, indicating that efficiency of energy
      conversion of PSII and photosynthetic electron transport was altered differently
      in the two genotypes. Short-term exposure to O3 had minimal effects on net carbon
      exchange rates of both soybean cultivars. A trend toward higher stomatal
      conductance in Mandarin (Ottawa) suggested stomatal exclusion might contribute to
      differential O3 sensitivity of the two genotypes. Increased sensitivity of
      Mandarin (Ottawa) to O3 was associated with higher H2 O2 and O2 (-) production
      compared with Fiskeby III, possibly associated with genotype differences in
      stomatal function or regulation of ethylene during the initial phases of O3
      response.

PMID- 25959716
TI  - PPAR-alpha agonist elicits metabolically active brown adipocytes and weight loss
      in diet-induced obese mice.
AB  - Obesity is considered a public health problem worldwide. Fenofibrate, a selective
      peroxisome proliferator-activated receptor alpha (PPAR-alpha) agonist, elicits
      weight loss in animal models. This study aimed to examine the effects of
      fenofibrate on energy expenditure, body mass (BM) and gene expression of
      thermogenic factors in brown adipose tissue of diet-induced obese mice. Male
      C57BL/6 mice were fed a standard chow (SC; 10% lipids) diet or a high-fat (HF;
      50% lipids) diet for 10 weeks. Afterwards, groups were subdivided as SC, SC-F, HF
      and HF-F (n = 10, each). Treatment with fenofibrate (100 mg kg(-1) BM mixed into
      the diet) lasted 5 weeks. Treated groups had reduced final BM compared with their
      counterparts (p < 0.05), explained by the increase in energy expenditure, CO2
      production and O2 consumption after treatment with fenofibrate (p < 0.05).
      Similarly, genes involved in thermogenesis as PPAR-alpha, PPAR-gamma coactivator
      1alpha, nuclear respiratory factor 1, mitochondrial transcription factor A
      (Tfam), PR domain containing 16 (PRDM16), beta-3 adrenergic receptor (beta3-AR),
      bone morphogenetic protein 8B and uncoupling protein 1 were significantly
      expressed in brown adipocytes after the treatment (p < 0.05). All observations
      ensure that selective PPAR-alpha agonist can induce thermogenesis by increasing
      energy expenditure and enhancing the expression of genes involved in the
      thermogenic pathway. These results suggest fenofibrate as a coadjutant drug for
      the treatment of obesity.

PMID- 25959720
TI  - Time-resolved IR spectroscopy of a trinuclear palladium complex in solution.
AB  - This paper presents a combined spectroscopic and theoretical analysis of a
      trinuclear [Pd3{Si(mt(Me))3}2] complex (mt(Me) = methimazole) which has been
      demonstrated to be a potential catalyst for coupling reactions. It is a highly
      symmetric model system (D3 in the electronic ground state) for the investigation
      of electronic states and the structure of polynuclear transition metal complexes.
      Different time-resolved IR spectroscopic methods covering the femtosecond up to
      the microsecond range as well as density functional computations are performed to
      unravel the structure and character of this complex in the electronically excited
      state. These are the first time-resolved IR studies on a trinuclear Pd complex.
      Based on the interplay between the computational results and those from the IR
      studies a (3)A state is identified as the lowest lying triplet state which has C2
      symmetry. 

PMID- 25959719
TI  - Reflectance confocal microscopy as a useful diagnostic tool for monitoring of
      skin containing vascularized composite allograft rejection: A preliminary study
      on rats.
AB  - Vascularized composite allografts can undergo immune-mediated rejection, and skin
      biopsies are needed for monitoring of the transplant. However it is an invasive
      method, and requires processing time and pathological assessment. The purpose of
      this study is to use a new noninvasive monitoring method of the reflectance
      confocal microscopy (RCM) to determine severity of the allograft rejection on
      rats. Five groin flap allotransplantation were performed between 10 male Sprague
      Dawley rats. Immunosuppressive therapy with cyclosporine A was given to the
      recipients during 10 days after surgery and was ended at the 10th postoperative
      days to allow acute transplant rejection. Following cessation of CsA, concomitant
      RCM evaluation and skin biopsy was performed every other day from each animal
      until total rejection of the allograft. Complete rejection of the allograft took
      nearly about 10 days and 4 or 5 RCM evaluation and skin biopsy was performed from
      each rat during this period. A total of 17 specimens were evaluated. A scoring
      system was developed based on the RCM findings. Skin biopsies were evaluated
      according to the Banff 2007 working classification criteria. RCM evaluation
      revealed epidermal irregularity and collagen destruction, however mild
      perivascular inflammation and degeneration of the basal epidermal layer were
      observed in early and late rejection period respectively with histopathologic
      evaluation. High correlation was found between the RCM scores and histopathologic
      grading. The RCM may be the useful tool to reduce the need for skin biopsy for
      monitoring of the skin containing vascularized composite allograft.

PMID- 25959721
TI  - N-Heterocyclic carbene-catalyzed [2+3] cyclocondensation of alpha-chloroaldehydes
      with azomethine imines.
AB  - An N-heterocyclic carbene-catalyzed enantioselective [2+3] cyclocondensation of
      alpha-chloroaldehydes with azomethine imines was developed. The corresponding
      pyrazolidinones were obtained in good yields with moderate to good
      diastereoselectivities and excellent enantioselectivities. 

PMID- 25959722
TI  - Co-administration of deflazacort and doxycycline: a potential pharmacotherapy for
      Duchenne muscular dystrophy.
AB  - The standard therapy used in the treatment of Duchenne muscle dystrophy (DMD) is
      corticoids, such as deflazacort and prednisone. However, they have limited
      therapeutic value, and their combination with drugs already in use to treat other
      human diseases could potentially increase corticoid outcomes in DMD. In the
      present study, we evaluated whether a combined therapy of the corticoid
      deflazacort with doxycycline could result in greater improvement in mdx dystrophy
      than deflazacort alone. Deflazacort alone or deflazacort/doxycycline were
      administered for 36 days (starting on postnatal day 0) in drinking water.
      Histopathological, biochemical (creatine kinase), functional (forelimb muscle
      grip strength and fatigue) parameters and inflammatory markers (MMP-9, TNF-alpha,
      NF-kB) were evaluated in biceps brachii and diaphragm muscles of the mdx mice.
      The combined therapy was superior in improving the dystrophic phenotype compared
      to monotherapy. The primary results were observed in attenuating muscle fatigue,
      decreasing muscle total calcium and inflammatory markers and increasing beta
      dystroglycan, a main component of the dystrophin-protein complex. Furthermore,
      the combined therapy was effective in preventing the loss of body mass observed
      with deflazacort alone at this very early stage of therapy. The present study
      offers preclinical data to support further studies with deflazacort/doxycycline
      combined therapy in DMD clinical trials.

PMID- 25959723
TI  - Reactivity of cationic agostic and carbene structures derived from platinum(II)
      metallacycles.
AB  - This paper describes the formation of new platinacyclic complexes derived from
      the phosphine ligands PiPr2 Xyl, PMeXyl2 , and PMe2 Ar Xyl 2 (Xyl=2,6-Me2 C6 H3
      and Ar Xyl 2=2,6-(2,6-Me2 C6 H3 )2 -C6 H3 ) as well as reactivity studies of the
      trans-[Pt(C^P)2 ] bis-metallacyclic complex 1 a derived from PiPr2 Xyl.
      Protonation of compound 1 a with [H(OEt2 )2 ][BArF ] (BArF =B[3,5-(CF3 )2 C6 H3
      ]4 ) forms a cationic delta-agostic structure 4 a, whereas alpha-hydride
      abstraction employing [Ph3 C][PF6 ] produces a cationic platinum carbene trans
      [Pt{PiPr2 (2,6-CH(Me)C6 H3 }{PiPr2 (2,6-CH2 (Me)C6 H3 }][PF6 ] (8). Compounds 4 a
      and 8 react with H2 to yield the same 1:3 equilibrium mixture of 4 a and trans
      [PtH(PiPr2 Xyl)2 ][BArF ] (6), in which one of the phosphine ligands participates
      in a delta-agostic interaction. DFT calculations reveal that H2 activation by 8
      occurs at the highly electrophilic alkylidene terminus with no participation of
      the metal. The two compounds 4 a and 8 experience C-C coupling reactions of a
      different nature. Thus, 4 a gives rise to complex trans-[PtH{(E)-1,2-bis(2-(PiPr2
      )-3-MeC6 H3 )CH?CH}] (7) that contains a tridentate diphosphine-alkene ligand,
      through agostic C?H oxidative cleavage and C-C reductive coupling steps, whereas
      the C-C coupling reaction in 8 involves classical migratory insertion of its
      [Pt?CH] and [Pt?CH2 ] bonds promoted by platinum coordination of CO or CNXyl. The
      mechanisms of the C?C bond-forming reactions have also been investigated by
      computational methods. 

PMID- 25959724
TI  - Time to eligibility for antiretroviral therapy in adults with CD4 cell count >
      500 cells/MUL in rural KwaZulu-Natal, South Africa.
AB  - OBJECTIVES: Understanding of progression to antiretroviral therapy (ART)
      eligibility and associated factors remains limited. The objectives of this
      analysis were to determine the time to ART eligibility and to explore factors
      associated with disease progression in adults with early HIV infection. METHODS:
      HIV-infected adults (>= 18 years old) with CD4 cell count > 500 cells/MUl were
      enrolled in the study at three primary health care clinics, and a
      sociodemographic, behavioural and partnership-level questionnaire was
      administered. Participants were followed 6-monthly and ART eligibility was
      determined using a CD4 cell count threshold of 350 cells/MUl. Kaplan - Meier and
      Cox proportional hazard regression modelling were used in the analysis. RESULTS:
      A total of 206 adults contributed 381 years of follow-up; 79 (38%) reached the
      ART eligibility threshold. Median time to ART eligibility was shorter for male
      patients (12.0 months) than for female patients (33.9 months). Male sex [adjusted
      hazard ratio (aHR) 3.13; 95% confidence interval (CI) 1.82-5.39], residing in a
      household with food shortage in the previous year (aHR 1.58; 95% CI 0.99-2.54),
      and taking nutritional supplements in the first 6 months after enrolment (aHR
      2.06; 95% CI 1.11-3.83) were associated with shorter time to ART eligibility.
      Compared with reference CD4 cell count <=  559 cells/MUl, higher CD4 cell count
      was associated with longer time to ART eligibility [aHR 0.46 (95% CI 0.25-0.83)
      for CD4 cell count 560-632 cells/MUl; aHR 0.30 (95% CI 0.16-0.57) for CD4 cell
      count 633-768 cells/MUl; and aHR 0.17 (95% CI 0.08-0.38) for CD4 cell count > 768
      cells/MUl]. CONCLUSIONS: Over one in three adults with CD4 cell count > 500
      cells/MUl became eligible for ART at a CD4 cell count threshold of 350 cells/MUl
      over a median of 2 years. The shorter time to ART eligibility in male patients
      suggests a possible need for sex-specific pre-ART care and monitoring strategies.

PMID- 25959725
TI  - Orthogonal light-induced self-assembly of nanoparticles using differently
      substituted azobenzenes.
AB  - Precise control of the self-assembly of selected components within complex
      mixtures is a challenging goal whose realization is important for fabricating
      novel nanomaterials. Herein we show that by decorating the surfaces of metallic
      nanoparticles with differently substituted azobenzenes, it is possible to
      modulate the wavelength of light at which the self-assembly of these
      nanoparticles is induced. Exposing a mixture of two types of nanoparticles, each
      functionalized with a different azobenzene, to UV or blue light induces the
      selective self-assembly of only one type of nanoparticles. Irradiation with the
      other wavelength triggers the disassembly of the aggregates, and the simultaneous
      self-assembly of nanoparticles of the other type. By placing both types of
      azobenzenes on the same nanoparticles, we created unique materials ("frustrated"
      nanoparticles) whose self-assembly is induced irrespective of the wavelength of
      the incident light. 

PMID- 25959726
TI  - Performance and ERP components in the equiprobable go/no-go task: Inhibition in
      children.
AB  - The equiprobable go/no-go task lacks the dominant go imperative found in the
      usual go/no-go task, and hence we previously regarded it as involving little
      inhibition. However, children have relative difficulty with this task, and
      demonstrate large frontal no-go N2s. We investigated whether this child N2 plays
      an inhibitory role, using performance measures to illuminate the link between N2
      and inhibition. Forty children aged 8 to 13 were presented with four stimulus
      blocks each containing 75 go and 75 no-go tone stimuli in random order. A
      temporal PCA with unrestricted varimax rotation quantified the mean go and no-go
      ERP component amplitudes. Most identified components were differentially enhanced
      to go or no-go as in adults, supporting a previously proposed differential
      processing schema. Between subjects, larger frontocentral no-go N2bs were
      associated with fewer commission errors. Hence, the no-go N2b in this paradigm
      can be interpreted as an individual marker of inhibition in children. 

PMID- 25959727
TI  - Measuring the foundations of school readiness: Introducing a new questionnaire
      for teachers - The Brief Early Skills and Support Index (BESSI).
AB  - BACKGROUND: Early work on school readiness focused on academic skills. Recent
      research highlights the value of also including both children's social and
      behavioural competencies and family support. AIMS: Reflecting this broader
      approach, this study aimed to develop a new and brief questionnaire for teachers:
      The Brief Early Skills and Support Index (BESSI). SAMPLE: The main sample,
      recruited from the north-west of England, included 1,456 children (49% male),
      aged 2.5 to 5.5 years. A second sample consisting of 258 children (44% male) aged
      3 to 5.5 years was recruited to assess the test-retest reliability of the BESSI
      across a 1-month interval. METHODS: Following development and pilot work with
      early years teachers, a streamlined (30 items) version of the BESSI was sent to
      98 teachers and nursery staff, who rated the children in their class. RESULTS:
      The best-fitting model included four latent factors: Three child factors
      (Behavioural Adjustment, Language and Cognition, and Daily Living Skills) and one
      Family Support factor. The three child factors exhibited measurement invariance
      across gender. All four factors showed good internal consistency and test-retest
      reliability. Structural equation modelling showed that (1) boys had more problems
      than girls on all three child factors; (2) older children showed better Language
      and Cognition and Daily Living Skills than younger children; and (3) children
      eligible for free school meals (an index of financial hardship) had more problems
      on all four latent factors. Family Support latent scores predicted all three
      child latent factors and accounted for their correlation with financial hardship.
      CONCLUSIONS: The BESSI is a promising brief teacher-report screening tool that
      appears suitable for children aged 2.5 to 5.5 and provides a broader perspective
      upon school readiness than previous measures.

PMID- 25959728
TI  - Magnetothermally responsive star-block copolymeric micelles for controlled drug
      delivery and enhanced thermo-chemotherapy.
AB  - Magnetothermally responsive drug-loaded micelles were designed and prepared for
      cancer therapy. These specially designed micelles are composed of the thermo
      responsive star-block copolymer poly(epsilon-caprolactone)-block-poly(2-(2
      methoxyethoxy)ethyl methacrylate-co-oligo(ethylene glycol)methacrylate) and Mn,
      Zn doped ferrite magnetic nanoparticles (MZF-MNPs). The thermo-responses of 6sPCL
      b-P(MEO2MA-co-OEGMA) copolymers were shown to be dependent on the MEO2MA to OEGMA
      ratio. The lower critical solution temperature (LCST) of the star-block
      copolymers was controlled at 43  degrees C by adjusting the feed molar ratios of
      MEO2MA/OEGMA at 92 : 8. With the anti-tumor drug doxorubicin (DOX) self
      assembling into the carrier system, the thermo-responsive micelles exhibited
      excellent temperature-triggered drug release behavior. In vitro cytotoxicity
      results showed high biocompatibility of the polymer micelles. Efficient cellular
      proliferation inhibition by the drug-loaded micelles was found on the HepG2 cells
      under different treatments. The thermo-responsive polymer micelles are promising
      for controlled drug delivery in tumor therapy under an alternating magnetic
      field. 

PMID- 25959729
TI  - Nucleus to Synapse Nesprin1 Railroad Tracks Direct Synapse Maturation through RNA
      Localization.
AB  - An important mechanism underlying synapse development and plasticity is the
      localization of mRNAs that travel from the nucleus to synaptic sites. Here we
      demonstrate that the giant nuclear-associated Nesprin1 (dNesp1) forms striated F
      actin-based filaments, which we dubbed "railroad tracks," that span from muscle
      nuclei to postsynaptic sites at the neuromuscular junction in Drosophila. These
      railroad tracks specifically wrap around immature boutons formed during
      development and in response to electrical activity. In the absence of dNesp1,
      mRNAs normally localized at postsynaptic sites are lacking and synaptic
      maturation is inhibited. This dNesp1 function does not depend on direct
      association of dNesp1 isoforms with the nuclear envelope. We also show that
      dNesp1 functions with an unconventional myosin, Myo1D, and that both dNesp1 and
      Myo1D are mutually required for their localization to immature boutons. These
      studies unravel a novel pathway directing the transport of mRNAs from the nucleus
      to postsynaptic sites during synaptic maturation. VIDEO ABSTRACT. 

PMID- 25959731
TI  - Dynamic Control of Response Criterion in Premotor Cortex during Perceptual
      Detection under Temporal Uncertainty.
AB  - Under uncertainty, the brain uses previous knowledge to transform sensory inputs
      into the percepts on which decisions are based. When the uncertainty lies in the
      timing of sensory evidence, however, the mechanism underlying the use of
      previously acquired temporal information remains unknown. We study this issue in
      monkeys performing a detection task with variable stimulation times. We use the
      neural correlates of false alarms to infer the subject's response criterion and
      find that it modulates over the course of a trial. Analysis of premotor cortex
      activity shows that this modulation is represented by the dynamics of population
      responses. A trained recurrent network model reproduces the experimental findings
      and demonstrates a neural mechanism to benefit from temporal expectations in
      perceptual detection. Previous knowledge about the probability of stimulation
      over time can be intrinsically encoded in the neural population dynamics,
      allowing a flexible control of the response criterion over time.

PMID- 25959730
TI  - Functional assembly of accessory optic system circuitry critical for compensatory
      eye movements.
AB  - Accurate motion detection requires neural circuitry that compensates for global
      visual field motion. Select subtypes of retinal ganglion cells perceive image
      motion and connect to the accessory optic system (AOS) in the brain, which
      generates compensatory eye movements that stabilize images during slow visual
      field motion. Here, we show that the murine transmembrane semaphorin 6A (Sema6A)
      is expressed in a subset of On direction-selective ganglion cells (On DSGCs) and
      is required for retinorecipient axonal targeting to the medial terminal nucleus
      (MTN) of the AOS. Plexin A2 and A4, two Sema6A binding partners, are expressed in
      MTN cells, attract Sema6A(+) On DSGC axons, and mediate MTN targeting of
      Sema6A(+) RGC projections. Furthermore, Sema6A/Plexin-A2/A4 signaling is required
      for the functional output of the AOS. These data reveal molecular mechanisms
      underlying the assembly of AOS circuits critical for moving image perception. 

PMID- 25959732
TI  - Theta Burst Firing Recruits BDNF Release and Signaling in Postsynaptic CA1
      Neurons in Spike-Timing-Dependent LTP.
AB  - Timing-dependent LTP (t-LTP) is a physiologically relevant type of synaptic
      plasticity that results from repeated sequential firing of action potentials
      (APs) in pre- and postsynaptic neurons. t-LTP can be observed in vivo and is
      proposed to be a cellular correlate of memory formation. While brain-derived
      neurotrophic factor (BDNF) is essential to high-frequency stimulation-induced LTP
      in many brain areas, the role of BDNF in t-LTP is largely unknown. Here, we
      demonstrate a striking change in the expression mechanism of t-LTP in CA1 of the
      hippocampus following two distinct modes of synaptic activation. Single
      postsynaptic APs paired with presynaptic stimulation activated a BDNF-independent
      canonical t-LTP. In contrast, a theta burst of postsynaptic APs preceded by
      presynaptic stimulation elicited BDNF-dependent postsynaptic t-LTP that relied on
      postsynaptic BDNF secretion. This suggests that BDNF release during burst-like
      patterns of activity typically observed in vivo may play a crucial role during
      memory formation.

PMID- 25959733
TI  - Contactin-4 mediates axon-target specificity and functional development of the
      accessory optic system.
AB  - The mammalian eye-to-brain pathway includes more than 20 parallel circuits, each
      consisting of precise long-range connections between specific sets of retinal
      ganglion cells (RGCs) and target structures in the brain. The mechanisms that
      drive assembly of these parallel connections and the functional implications of
      their specificity remain unresolved. Here we show that in the absence of
      contactin 4 (CNTN4) or one of its binding partners, amyloid precursor protein
      (APP), a subset of direction-selective RGCs fail to target the nucleus of the
      optic tract (NOT)--the accessory optic system (AOS) target controlling horizontal
      image stabilization. Conversely, ectopic expression of CNTN4 biases RGCs to
      arborize in the NOT, and that process also requires APP. Our data reveal critical
      and novel roles for CNTN4/APP in promoting target-specific axon arborization, and
      they highlight the importance of this process for functional development of a
      behaviorally relevant parallel visual pathway.

PMID- 25959735
TI  - Valid randomization-based p-values for partially post hoc subgroup analyses.
AB  - By 'partially post-hoc' subgroup analyses, we mean analyses that compare existing
      data from a randomized experiment-from which a subgroup specification is derived
      to new, subgroup-only experimental data. We describe a motivating example in
      which partially post hoc subgroup analyses instigated statistical debate about a
      medical device's efficacy. We clarify the source of such analyses' invalidity and
      then propose a randomization-based approach for generating valid posterior
      predictive p-values for such partially post hoc subgroups. Lastly, we investigate
      the approach's operating characteristics in a simple illustrative setting through
      a series of simulations, showing that it can have desirable properties under both
      null and alternative hypotheses.

PMID- 25959734
TI  - Specification of individual adult motor neuron morphologies by combinatorial
      transcription factor codes.
AB  - How the highly stereotyped morphologies of individual neurons are genetically
      specified is not well understood. We identify six transcription factors (TFs)
      expressed in a combinatorial manner in seven post-mitotic adult leg motor neurons
      (MNs) that are derived from a single neuroblast in Drosophila. Unlike TFs
      expressed in mitotically active neuroblasts, these TFs do not regulate each
      other's expression. Removing the activity of a single TF resulted in specific
      morphological defects, including muscle targeting and dendritic arborization, and
      in a highly specific walking defect in adult flies. In contrast, when the
      expression of multiple TFs was modified, nearly complete transformations in MN
      morphologies were generated. These results show that the morphological
      characteristics of a single neuron are dictated by a combinatorial code of
      morphology TFs (mTFs). mTFs function at a previously unidentified regulatory tier
      downstream of factors acting in the NB but independently of factors that act in
      terminally differentiated neurons. 

PMID- 25959736
TI  - [Cutaneous cryptococcosis mimicking basal cell carcinoma and revealing systemic
      involvement in acquired immunodeficiency].
AB  - BACKGROUND: Cryptococcosis is a rare and a serious opportunistic infection that
      occurs primarily on the field of immunodeficiency. We report a case of
      disseminated cryptococcosis in acquired immunodeficiency syndrome revealed by
      unusual skin lesions. OBSERVATION: A 52-year-old patient consulted for two crusty
      ulcerative lesions situated on the left supraorbital and on the nasal tip that
      appeared 6 months ago. He also reported respiratory symptoms present since one
      year, with dry cough and dyspnea, chronic headache and vomiting with no
      alteration in visual acuity. The mycological study of the skin biopsy on both
      lesions isolated Cryptococcus neoformans as well as in the sputum and
      cerebrospinal fluid. Serology of human immunodeficiency virus infection was
      positive. Treatment with fluconazole, local care and antiretroviral triple
      therapy was implemented. DISCUSSION: Skin lesions during cryptococcosis are rare
      and observed in 2-10% of cases. Cutaneous symptoms were the reason for
      consultation in our patient. This is a rare form of cutaneous cryptococcosis
      leading to the discovery of both pulmonary and central nervous system locations,
      and to diagnosis of HIV infection.

PMID- 25959737
TI  - The reconstructed edges of the hexagonal BN.
AB  - As an important two-dimensional material which shows exceptional mechanical and
      chemical stability, superior electronic properties, along with broad
      applications, the hexagonal-BN (h-BN) has drawn great attention recently. Here we
      report a systematic study on the structural stability, electronic and magnetic
      properties of various h-BN edges, including both bare and hydrogen-terminated
      ones. It is found that along the armchair (AC) direction, the pristine edge is
      the most stable one because of the formation of a triple B=N bond, while, along
      the zigzag (ZZ) directions, the reconstructed ones, ZZB + N and ZZN57 are more
      stable. The pristine edges are more stable in bare BN in most cases if saturated
      with hydrogen. By applying the theory of Wulff construction, we predicted that an
      unpassivated BN domain prefers the hexagonal shape enclosed with bare AC edges
      i.e., AC-Ns, AC, AC-Bs if the feedstock varies from N-rich to B-rich. However,
      the evolution from ZZN edged triangular domain, to hexagonal domain enclosed with
      AC edges, and ZZB edged triangle may occur if the edges are terminated by
      hydrogen atoms. Further calculation shows that these edges present rich type
      dependent properties and thus are important for various applications. This
      theoretical study showed that controlling the morphologies of BN domains and BN
      edges is crucial for various applications.

PMID- 25959738
TI  - Long-term results of a prospective randomized trial assessing the impact of re
      adaptation of the dorsolateral peritoneal layer after extended pelvic lymph node
      dissection and cystectomy.
AB  - OBJECTIVE: To evaluate the long-term oncological and functional outcomes of re
      adaptation of the dorsolateral peritoneal layer after pelvic lymph node
      dissection (PLND) and cystectomy. PATIENTS AND METHODS: A randomized, single
      centre, single-blinded, two-arm trial was conducted on 200 consecutive patients
      who underwent PLND and cystectomy for bladder cancer (<cT4, cN0, cM0) between
      April 2006 and September 2009. Patients were randomized into two groups: group A
      with re-adaptation of the dorsolateral peritoneal layer (n = 100; 73 male, 27
      female; median [range] age 68 [35-86] years) and group B without re-adapation (n
      = 100; 66 male, 34 female; median [range] age 65 [30-86] years). Regular
      postoperative follow-up was performed at our outpatient clinic. The median follow
      up was 59 (3-100) months. Five patients were lost to follow-up in group A and
      seven in group B. Bowel function was evaluated using the validated
      Gastrointestinal Quality of Life Index questionnaire and an institutional
      questionnaire regarding post-cystectomy outcome. Local recurrences and distal
      metastases were evaluated using computed tomography and bone scan at the regular
      follow-up visits. RESULTS: There was no significant difference between the two
      groups in terms of the rate of local (pelvic) recurrence (5/95 [5.3%] in group A;
      7/93 [7.5%] in group B; P = 0.53), the rate of distant metastases (21/95 [22.1%]
      in group A; 23/93 [24.7%] in group B; P = 0.67), cancer-specific survival (P =
      0.37) or overall survival (P = 0.59). Group A had significantly better bowel
      function at 3 (P < 0.001), 6 (P < 0.006), 12 (P < 0.006) and 24 months (P =
      0.04), and significantly less postoperative abdominal pain and bloating at 3 (P =
      0.002) and 6 months (P = 0.01). CONCLUSION: Re-adaptation of the dorsolateral
      peritoneal layer after PLND and cystectomy has a beneficial long-term impact on
      bowel function and postoperative pain without compromising oncological
      radicality.

PMID- 25959739
TI  - Earlier onset of diabesity-Induced adverse cardiac remodeling in female compared
      to male mice.
AB  - OBJECTIVE: Emerging evidence suggests female type 2 diabetes (T2DM) patients may
      fare worse than males with respect to cardiovascular complications. Hence the
      impact of sex on relative progression of left ventricular (LV) remodeling in
      obese db/db mice was characterized. METHODS: The changes in parameters of LV
      hypertrophy (heart weight, pro-hypertrophic gene expression, cardiomyocyte size)
      and fibrosis (LV collagen deposition and oxidative stress), in parallel with body
      weight and blood glucose and lipid profiles, in male and female db/db T2DM mice,
      at 10, 14, and 18 weeks of age, were determined. RESULTS: Diabesity-induced
      cardiac remodeling was at least comparable in female (compared to male) mice.
      Females exhibited enhanced systemic oxidative stress and nonesterified fatty acid
      levels. Progression of LV pro-hypertrophic (beta-myosin heavy chain, B-type
      natriuretic peptide) and pro-oxidant gene expression (NADPH oxidase subunit Nox2,
      plasminogen activator inhibitor-1 PAI-I) was, however, exaggerated in females
      when expressed relative to 10-week-old db/db mice. Increased cardiomyocyte width
      was also evident earlier in db/db females than males. No other gender differences
      were observed. CONCLUSIONS: Progressive, age-dependent development of cardiac
      remodeling in db/db mice parallels impairments in glucose handling and oxidative
      stress. Certain aspects of the T2DM-induced LV remodeling response may have an
      earlier and/or exaggerated onset in diabetic females.

PMID- 25959740
TI  - Bronchial myeloid sarcoma with concurrent Aspergillus fumigatus infection in a
      patient presenting with hemoptysis.
AB  - Myeloid sarcoma (MS) is an extramedullary myeloid neoplasm characterized by
      proliferation of myeloblasts which can occur in any organ or site. Bronchial and
      pulmonary involvement, however, is uncommon. We describe a case of bronchial MS
      in an 81-year-old female with a history of high-grade myelodysplastic syndrome;
      she was started on treatment few months before, and she presented with fever,
      cough and profuse hemoptysis. She was found to be pancytopenic with bilateral
      airspace consolidations, most notably in the right upper and lower lobes, on
      imaging studies. She was treated with broad-spectrum antibiotics and antifungals
      without much improvement in her clinical or radiological status. Ultimately,
      biopsy of the lung lesions showed myeloid sarcoma with concurrent Aspergillus
      fumigatus infection. Bronchial/pulmonary MS should be considered in the list of
      differential diagnoses in a patient with a history of myeloid neoplasm and
      presenting with respiratory related symptoms, as early administration of
      chemotherapy may help to improve survival rates. 

PMID- 25959741
TI  - FGFR as potential target in the treatment of squamous non small cell lung cancer.
AB  - To date therapeutic options for squamous cell lung cancer patients remain scarce
      because no druggable targets have been identified so far. Aberrant signaling by
      FGFs (fibroblast growth factors) and FGFRs (fibroblast growth factors receptors)
      has been implicated in several human cancers and, particularly, in squamous non
      small cell lung cancer (NSCLC). FGFR gene amplifications, somatic missense
      mutations, chromosomal translocations are the most frequent mechanisms able to
      induce aberrant activation of this pathway. Data from literature have established
      that the presence of an aberrant FGFR signaling has to be considered a possible
      negative prognostic factor but predictive of potential sensitivity to FGFR
      inhibitors. In the last years, clinical research efforts allowed to identify and
      evaluate promising FGFR inhibitors, such as monoclonal antibodies, ligand traps,
      non-selective or selective tyrosine kinase inhibitors. This review summarizes the
      current knowledge about FGFR alterations in NSCLC and the relative inhibitors in
      development, in particular in squamous NSCLC. 

PMID- 25959744
TI  - Side-to-side jejunojejunostomy is favorable for scope insertion during endoscopic
      retrograde cholangiopancreatography in patients with Roux-en-Y
      hepaticojejunostomy.

PMID- 25959743
TI  - Value of a small control group for estimating intervention effectiveness: results
      from simulations of immunization effectiveness studies.
AB  - AIM: To improve evidence for public health practice, the conduct of effectiveness
      studies by practitioners is needed and may be stimulated if knowledge that
      smaller than usual samples may provide the same reliability of intervention
      effect size as larger samples. MATERIALS & METHODS: We examined reliability of
      intervention effect using computerized simulations of 2000 hypothetical
      immunization effectiveness studies from an actual study population and by small
      (30 and 60) and larger (100 and 200) control groups compared with an intervention
      group of 200 participants. RESULTS & CONCLUSION: Across simulated studies, the
      mean intervention effect (14%) and effect sizes were equivalent regardless of
      control group size and equal to the actual study effect. These results are
      relevant for similarly designed and executed studies and indicate that studies
      with smaller control groups can generate valid and accurate evidence for
      effective public health practice in communities.

PMID- 25959745
TI  - Quantum chemical insights into the dependence of porphyrin basicity on the meso
      aryl substituents: thermodynamics, buckling, reaction sites and molecular
      flexibility.
AB  - The chemical and sensing properties of porphyrins are frequently tuned via the
      introduction of peripheral substituents. In the context of the exceptionally fast
      second protonation step in the case of 5,10,15,20-tetraphenylporphyrin (TPP), as
      compared to porphin and 5,10,15,20-tetramesitylporphyrin (TMesP), we investigated
      the macrocycle-substituent interactions of these three porphyrin derivatives in
      detail. Using quantum chemical thermodynamics calculations, the analysis of
      geometric structures, torsional profiles, electrostatic potential distributions,
      and particularly the analysis of molecular flexibilities via ab initio molecular
      dynamics simulations, we obtained a comprehensive picture of the reactivities of
      the studied porphyrins and how these are influenced by the meso-substituents. As
      compared to porphin and TMesP the second protonation of TPP is energetically more
      favorable and is particularly energetically comparable to its first protonation,
      instead of being significantly less favorable like in the case of porphyrin and
      TMesP. Additionally, the second TPP protonation is facilitated by an interplay
      between out-of-plane (oop) distortion of the protonation site and a pronounced
      electrostatic binding spot at the protonation site. Furthermore, the second
      protonation is particularly facilitated in the case of TPP by the large oop
      flexibility of the diprotonated species as unraveled by ab initio molecular
      dynamics simulations. 

PMID- 25959742
TI  - Aspirin Action in Endothelial Cells: Different Patterns of Response Between
      Chemokine CX3CL1/CX3CR1 and TNF-alpha/TNFR1 Signaling Pathways.
AB  - PURPOSE: TNF-alpha induces fractalkine (CX3CL1) and its receptor CX3CR1 in
      endothelial cells through NF-?B activation. NF-?B inhibitors may reduce the
      expression of CX3CL1, and modulation of the CX3CL1/CX3CR1 signaling was proposed
      as a new target for aspirin. We examined the effects of aspirin on CX3CL1 and TNF
      alpha production, as well as CX3CR1 and TNFR1 expression. METHODS: HUVECs
      isolated after term pregnancies (N = 28) were cultured in vitro.
      Lipopolysaccharide (1 MUg/ml) was used as CX3CL1 inducer. HUVECs were exposed to
      six different concentrations of aspirin (between 1.0 and 6.0 mM) during 7 days.
      The levels of CX3CL1 and TNF-alpha in the culture media were measured using
      ELISA. After termination of the cultures, mean expressions of CX3CR1 and TNFR1
      were examined in the immunostained paraffin sections using quantitative
      immunohistochemistry. RESULTS: Aspirin significantly (p <  .05) decreased CX3CL1
      production, and the mean decrease in CX3CL1 production was inversely proportional
      to increased (p < 0.05) expression of CX3CR1. The combined mean CX3CL1
      concentrations, including all time points, equaled 782.18 +/- 74.4 pg/ml in
      aspirin treated HUVECs compared to a total concentration of 2467.53 +/- 127.5
      pg/ml combined from the respective time points in the controls. An inhibition of
      TNF-alpha production in HUVECs after pretreatment with aspirin was observed.
      Unlike in the case of CX3CR1 expression, there were no signs of TNFR1
      upregulation. CONCLUSIONS: Autoregulation between CX3CL1 and CX3CR1 may explain
      overexpression of CX3CR1 as the compensatory effect in aspirin-treated HUVECs.
      Inhibition of CX3CR1 could prevent thrombotic complications in the early period
      after discontinuation of aspirin.

PMID- 25959746
TI  - pH-Responsive assembly of metal nanoparticles and fluorescent dyes by diblock
      copolymer micelles.
AB  - Hybrid assemblies consisting of metal nanoparticles (NPs) and fluorophores are
      quite interesting because the intrinsic properties of fluorophores can be
      engineered in the assembled structure. In this regard, we utilized the self
      segregation properties of block copolymer micelles to organize metal NPs and
      fluorophores simultaneously in a specific arrangement. From the viewpoint of
      assembly methods, we first encapsulated Au NPs in the PS cores of polystyrene
      block-poly(acrylic acid) (PS-PAA) micelles. Then, positively charged fluorescent
      dyes of rhodamine 123 (R123) were bound to the negatively charged PAA coronas by
      electrostatic interactions. Since carboxylic acid in the PAA block is a weak
      acid, the degree of R123 binding to PS-PAA micelles can be adjusted by varying
      the pH of the solution. Therefore, by changing the pH, we were able to control
      the assembly and disassembly of R123 molecules to PS-PAA micelles and the
      corresponding change in the fluorescence signal. 

PMID- 25959747
TI  - The effect of BCG on iron metabolism in the early neonatal period: A controlled
      trial in Gambian neonates.
AB  - Bacillus Calmette-Guerin (BCG) vaccination has been reported to protect neonates
      from non-tuberculous pathogens, but no biological mechanism to explain such
      effects is known. We hypothesised that BCG produces broad-spectrum anti-microbial
      protection via a hepcidin-mediated hypoferraemia, limiting iron availability for
      pathogens. To test this we conducted a trial in 120 Gambian neonates comparing
      iron status in the first 5-days of life after allocation to: (1) All routine
      vaccinations at birth (BCG/Oral Polio Vaccine (OPV)/Hepatitis B Vaccine (HBV));
      (2) BCG delayed until after the study period (at day 5); and (3) All routine
      vaccinations delayed until after the study period. Vaccine regime at birth did
      not significantly impact on any measured parameter of iron metabolism. However,
      the ability to detect an effect of BCG on iron metabolism may have been limited
      by short follow-up time and high activation of the inflammatory-iron axis in the
      study population. 

PMID- 25959748
TI  - Privileged scaffolds in lead generation.
AB  - INTRODUCTION: The term "privileged scaffold" was coined in 1988 and the strategy
      was to construct high-affinity ligands from core structures that can bind more
      than one receptor. Since then, the privileged scaffold-based design has evolved
      from a stand-alone technology to an integral component of various lead generation
      platforms. AREAS COVERED: In this review, the authors discuss the applications of
      the privileged scaffold concept in current lead generation. Specifically, the
      authors cover the role that privileged scaffolds have played in the mass
      production of compounds to feed high-throughput screening (HTS) and its role in
      the design of ligands targeting protein-protein interactions, multiple ligands
      and warhead-based ligands. It is not the intention of the authors to review all
      privileged scaffolds known to date. Rather, the aim of this review is to
      highlight the strategic value of the concept of privileged scaffolds in various
      contemporary lead generation platforms. EXPERT OPINION: The privileged scaffolds
      as described by the original definition proved abundant in the available chemical
      space. HTS and other screening methods, in addition to greatly enhanced compound
      collections, make privileged scaffold-based design less relevant in finding high
      affinity ligands than originally envisioned. However, the principle of privileged
      scaffolds has greatly enhanced and empowered current lead generation
      technologies.

PMID- 25959750
TI  - Dual Sulfide-Disulfide Crosslinked Networks with Rapid and Room Temperature Self
      Healability.
AB  - Polymer-based crosslinked networks with intrinsic self-repairing ability have
      emerged due to their built-in ability to repair physical damages. Here, novel
      dual sulfide-disulfide crosslinked networks (s-ssPxNs) are reported exhibiting
      rapid and room temperature self-healability within seconds to minutes, with no
      extra healing agents and no change under any environmental conditions. The method
      to synthesize these self-healable networks utilizes a combination of well-known
      crosslinking chemistry: photoinduced thiol-ene click-type radical addition,
      generating lightly sulfide-crosslinked polysulfide-based networks with excess
      thiols, and their oxidation, creating dynamic disulfide crosslinkages to yield
      the dual s-ssPxNs. The resulting s-ssPxN networks show rapid self-healing within
      30 s to 30 min at room temperature, as well as self-healing elasticity with
      reversible viscoelastic properties. These results, combined with tunable self
      healing kinetics, demonstrate the versatility of the method as a new means to
      synthesize smart multifunctional polymeric materials. 

PMID- 25959749
TI  - Mutations in RIT1 cause Noonan syndrome - additional functional evidence and
      expanding the clinical phenotype.
AB  - RASopathies are a clinically heterogeneous group of conditions caused by
      mutations in 1 of 16 proteins in the RAS-mitogen activated protein kinase (RAS
      MAPK) pathway. Recently, mutations in RIT1 were identified as a novel cause for
      Noonan syndrome. Here we provide additional functional evidence for a causal role
      of RIT1 mutations and expand the associated phenotypic spectrum. We identified
      two de novo missense variants p.Met90Ile and p.Ala57Gly. Both variants resulted
      in increased MEK-ERK signaling compared to wild-type, underscoring gain-of
      function as the primary functional mechanism. Introduction of p.Met90Ile and
      p.Ala57Gly into zebrafish embryos reproduced not only aspects of the human
      phenotype but also revealed abnormalities of eye development, emphasizing the
      importance of RIT1 for spatial and temporal organization of the growing organism.
      In addition, we observed severe lymphedema of the lower extremity and genitalia
      in one patient. We provide additional evidence for a causal relationship between
      pathogenic mutations in RIT1, increased RAS-MAPK/MEK-ERK signaling and the
      clinical phenotype. The mutant RIT1 protein may possess reduced GTPase activity
      or a diminished ability to interact with cellular GTPase activating proteins;
      however the precise mechanism remains unknown. The phenotypic spectrum is likely
      to expand and includes lymphedema of the lower extremities in addition to nuchal
      hygroma. 

PMID- 25959751
TI  - Pattern of association between endemic Hawaiian fruit flies (Diptera,
      Tephritidae) and their symbiotic bacteria: Evidence of cospeciation events and
      proposal of "Candidatus Stammerula trupaneae".
AB  - Several insect lineages have evolved mutualistic association with symbiotic
      bacteria. This is the case of some species of mealybugs, whiteflies, weevils,
      tsetse flies, cockroaches, termites, carpenter ants, aphids and fruit flies. Some
      species of Tephritinae, the most specialized subfamily of fruit flies (Diptera:
      Tephritidae), harbour co-evolved vertically transmitted, bacterial symbionts in
      their midgut, known as "Candidatus Stammerula spp.". The 25 described endemic
      species of Hawaiian tephritids, plus at least three undescribed species, are
      taxonomically distributed among three genera: the cosmopolitan genus Trupanea (21
      described spp.), the endemic genus Phaeogramma (2 spp.) and the Nearctic genus
      Neotephritis (2 spp.). We examined the presence of symbiotic bacteria in the
      endemic tephritids of the Hawaiian Islands, which represent a spectacular example
      of adaptive radiation, and tested the concordant evolution between host and
      symbiont phylogenies. We detected through PCR assays the presence of specific
      symbiotic bacteria, designated as "Candidatus Stammerula trupaneae", from 35
      individuals of 15 species. The phylogeny of the insect host was reconstructed
      based on two regions of the mitochondrial DNA (16S rDNA and COI-tRNALeu-COII),
      while the bacterial 16S rRNA was used for the symbiont analysis. Host and
      symbiont phylogenies were then compared and evaluated for patterns of cophylogeny
      and strict cospeciation. Topological congruence between Hawaiian Tephritinae and
      their symbiotic bacteria phylogenies suggests a limited, but significant degree
      of host-symbiont cospeciation. We also explored the character reconstruction of
      three host traits, as island location, host lineage, and host tissue attacked,
      based on the symbiont phylogenies under the hypothesis of cospeciation. 

PMID- 25959752
TI  - [The RELAX-AHF study].

PMID- 25959753
TI  - [Surgical treatment of ischemic mitral regurgitation].

PMID- 25959754
TI  - [European 2014 guidelines on the diagnosis and treatment of acute pulmonary
      embolism: underlying the importance of "patient-centered" clinical assessment as
      well as of new management and therapeutic approaches].

PMID- 25959755
TI  - [Surgical treatment of the thoracic aorta according to the 2014 European
      guidelines].

PMID- 25959756
TI  - [PCSK9 monoclonal antibody inhibition: current evidence and future perspectives
      of lipid-lowering therapy according to the available results from the ODYSSEY
      program].

PMID- 25959757
TI  - [Intramyocardial bridges: anatomo-pathological characteristics, diagnosis, and
      therapeutic strategies].
AB  - Intramyocardial bridge is defined as the segment of a major epicardial coronary
      artery that runs within the cardiac muscle wall (coronary tunneling). Usually,
      this kind of anatomic variant is asymptomatic but sometimes it may lead to acute
      coronary syndrome and/or arrhythmias, and more rarely to sudden cardiac death.
      Treatment for symptomatic patients is pharmacological, using beta-blockers. 

PMID- 25959758
TI  - [Metformin and left ventricular remodeling after acute myocardial infarction:
      molecular mechanisms and clinical implications].
AB  - Despite clear advances in reperfusion therapy and pharmacological treatment, a
      large proportion of patients with an acute myocardial infarction will die of its
      consequences. In this regard, it is very important to understand the molecular
      processes underpinning ischemia-reperfusion injury and occurrence of left
      ventricular dysfunction, with the aim to develop mechanism-based therapeutic
      strategies. Experimental evidence indicates that metformin, a biguanide often
      used in the treatment of diabetes, has favorable effects on left ventricular
      function. This effect is largely mediated by activation of AMP-activated protein
      kinase (AMPK), a key molecule orchestrating many biochemical processes such as
      glucose uptake, glycolysis, oxidation of free fatty acids and mitochondrial
      biogenesis. These processes significantly contribute to raise ATP levels and
      restore myocardial contractile efficiency. AMPK also activates endothelial nitric
      oxide synthase and promotes autophagy, thus preventing inflammation and cellular
      death. These basic studies prompted many researchers to test the cardioprotective
      effects of metformin in the clinical setting. In diabetic patients with ST
      elevation myocardial infarction (STEMI), retrospective analyses showed that
      metformin is associated with reduced infarct size as compared to non-metformin
      based strategies, implicating beneficial effects beyond glucose control. A recent
      randomized trial, the GIPS-III study, has postulated that metformin may improve
      left ventricular function following STEMI even in patients without diabetes.
      Metformin (500 mg twice/day), administered 3h after percutaneous coronary
      intervention, did not result in improved left ventricular ejection fraction after
      4-month follow-up. Based on these results, it remains unclear whether metformin
      exerts a cardioprotective effect regardless of glycemic control. Further
      randomized studies in diabetic and nondiabetic patients are required to address
      these important questions. The present review critically discusses established
      knowledge and evidence gaps on the effects of metformin on left ventricular
      function in diabetic and nondiabetic patients with myocardial infarction.

PMID- 25959759
TI  - [Patent ductus arteriosus].
AB  - The ductus arteriosus is a physiological structure allowing shunt of blood from
      the pulmonary artery to the descending aorta during fetal life (unventilated
      lung). The incidence of isolated patent ductus arteriosus (PDA) in children born
      at term is about 1 per 2000 live births, accounting for 5-10% of all congenital
      heart defects. The pathophysiological significance and management of PDA vary
      according to the clinical context (isolated anomaly or as part of complex
      congenital heart disease), magnitude of the shunt, and stadium within the natural
      history. This review summarizes the embryogenetic, pathophysiological, clinical
      and therapeutic basic concepts for an updated approach to this particular heart
      disease commonly seen even by the cardiologist of the adult. 

PMID- 25959760
TI  - [Achieving optimal cholesterol levels in patients with chronic ischemic heart
      disease: from guidelines to the real world].
AB  - BACKGROUND: It is known that less than half of patients with coronary heart
      disease reaches the target of LDL cholesterol (LDL-C) <100 mg/dl. According to
      the latest international guidelines, this target has been lowered to <70 mg/dl in
      very high-risk patients. METHODS: From November 1, 2009 to December 31, 2012,
      4953 patients with coronary heart disease were enrolled in the Cardiovascular
      Registry of Trieste (Italy). We assessed clinical data, LDL-C levels, statin
      prescription and medium-term outcome in patients with coronary heart disease.
      RESULTS: At first clinical evaluation, LDL-C values were available for only 61.5%
      of patients. The target level of LDL-C <70 mg/dl was reached in 17% of cases and
      LDL-C <100 mg/dl in 53%. Patients with lower LDL-C levels were more frequently
      males, with higher cardiovascular risk profile, more comorbidity and more
      frequent polypharmacy. LDL-C levels influenced statin prescription: in patients
      with LDL-C >= 100 mg/dl, cardiologists started or modified the dosage of statin
      therapy twice more than in patients with LDL-C <100 mg/dl, even if only in less
      than 20% of cases. Patients with LDL-C <100 mg/dl in statin therapy had better
      prognosis, whereas patients with low LDL-C levels without statin therapy had the
      worst prognosis. Other prognostic factors in this population with LDL-C <100
      mg/dl were age, presence of heart failure, comorbidities (evaluated with Charlson
      index) and polypharmacy. CONCLUSIONS: In our population of outpatients with
      coronary heart disease, the target of LDL-C <100 mg/dl was reached in 53% of
      cases. LDL-C levels influenced statin prescription and modification of dosages.
      The medium-term outcome is closely influenced by the achievement of target LDL-C
      levels and statin prescription.

PMID- 25959761
TI  - [Giant aneurysm of the right coronary artery: an unusual treatment].
AB  - Coronary artery aneurysm (CAA) is an uncommon disease observed in only 0.15-4.9%
      of patients undergoing coronary angiography. CAA are defined as dilated coronary
      artery sections exceeding by 1.5 times the diameter of normal adjacent segments
      or of the patient's largest coronary vessel. Occasionally, CAA enlarge enough to
      be called giant CAA. We report the case of a 78-year-old man, with known chronic
      ischemic cardiomyopathy and a history of prior coronary artery bypass surgery
      (with a left internal mammary artery graft to the left anterior descending
      coronary artery and saphenous venous graft to the obtuse marginal branch), who
      was referred to our cardiology department for progressive dyspnea.
      Echocardiography showed severe mitral regurgitation suggesting replacement;
      coronary angiography revealed three-vessel coronary artery disease, left internal
      mammary artery patency, saphenous vein graft occlusion and an aneurysm of the mid
      right coronary artery. Cardiac magnetic resonance confirmed this finding, showing
      a giant CAA (65 x 75 mm) with a large endoluminal thrombus. Treatment is not
      standardized and may include medical therapy, percutaneous treatment and surgical
      intervention; our patient underwent percutaneous coil embolization. One-month
      angiographic follow-up showed successful obliteration. The patient underwent
      surgical mitral valve replacement without any complications. At 9-month clinical
      follow-up, he was asymptomatic; transthoracic echocardiography showed an ejection
      fraction of 44% without prosthetic mitral regurgitation.

PMID- 25959762
TI  - [Mitral valvuloplasty in a patient with congenital kyphoscoliosis: case report
      and literature review].
AB  - Percutaneous transluminal mitral commissurotomy (PTMC) is the procedure of choice
      for the treatment of severe mitral stenosis in symptomatic patients. In recent
      years, epidemiological changes among these patients are observed, since they more
      frequently are older, with several comorbidities and unfavorable mitral anatomy,
      all features that may contraindicate PTMC. Notwithstanding this, high rates of
      success and safety are achieved, following improvements in the learning curve and
      technique. We report the case of a 68-year-old Caucasian male, affected by
      chronic obstructive pulmonary disease and congenital kyphoscoliosis, admitted for
      acute pulmonary edema in severe mitral valve stenosis and moderate mitral
      regurgitation. PTMC was performed successfully, without any complications, using
      few simple tricks. 

PMID- 25959763
TI  - [Interrupted aortic arch in a 68-year-old female with hypertension].
AB  - Interrupted aortic arch (IAA) is a rare congenital malformation of the aorta and
      aortic arch. We report the case of a 68-year-old female with hypertension and
      poor control of blood pressure levels. She was diagnosed with aortic coarctation
      by aortography during young age. A double access angiography was performed that
      showed a type A IAA, a rare condition in adults that may cause hypertension. 

PMID- 25959765
TI  - Sustained improvements in fitness and exercise tolerance in obese adolescents
      after a 12 week exercise intervention.
AB  - A 12 week exercise program was evaluated for its effect on aerobic fitness,
      anaerobic threshold, physical activity and sedentary behavior levels in obese
      insulin resistant adolescents post intervention and at follow up. 111 obese
      insulin resistant 10-17 year olds were recruited to a 12 month lifestyle
      intervention, known as RESIST. From months 4 to 6, adolescents participated in
      supervised exercise sessions twice per week (45-60min/session). Aerobic fitness
      and anaerobic threshold were measured by gas analysis at baseline, 6 months (post
      intervention) and 12 months (follow up). Self-reported physical activity and
      sedentary behavior was measured using the CLASS questionnaire. At 6 months
      aerobic fitness and time to reach the anaerobic threshold had improved by 5.8%
      [95% CI: 0.8-11.3] and 19.7% [95% CI: 10.4-29.0], respectively compared with
      baseline. These improvements were maintained at 12 months. Compared to baseline,
      6 month physical activity levels increased by 19min/day [95% CI: 5-33] and screen
      time decreased by 49min/day [95% CI: 23-74] but returned to baseline levels by 12
      months. Improved fitness and anaerobic threshold can be sustained up to 6 months
      following completion of an exercise program possibly enhancing capacity to
      perform daily functional tasks.

PMID- 25959767
TI  - Italian Ministry of Health and the Istituto Superiore Di Sanita: from vigilance
      to ownership?

PMID- 25959766
TI  - Identification of enzymes involved in SUMOylation in Trypanosoma brucei.
AB  - Small ubiquitin-like modifier (SUMO), a reversible post-translational protein
      modifier, plays important roles in diverse cellular mechanisms. Three enzymes, E1
      (activating enzyme), E2 (conjugating enzyme) and E3 (ligase), are involved in
      SUMO modification. SUMOylation system and process in higher eukaryotes have been
      well studied. However, in protozoa, such as Trypanosoma brucei (T. brucei), these
      remain poorly understood. Herein, we identified the E1 (TbAos1/TbUba2) and E2
      (TbUbc9) enzymes of SUMOylation pathway in T. brucei by sequence analysis and GST
      pull-down assay. Furthermore, we successfully reconstructed the SUMOylation
      system in vitro with recombinant enzymes. Using this system, the active site of
      TbUba2 and TbUbc9 was revealed to be located at Cys343 and Cys132, respectively,
      and a centrin homologue (TbCentrin3) was identified to be a target of SUMOylation
      in T. brucei. Altogether, our results demonstrate that TbAos1/TbUba2 and TbUbc9
      are the bona fide E1 and E2 enzymes of the SUMOylation system in T. brucei. 

PMID- 25959768
TI  - Matrix-free synthesis of spin crossover micro-rods showing a large hysteresis
      loop centered at room temperature.
AB  - An original simple homogeneous acid medium was used to synthesize
      polymer/surfactant-free acicular micro-rod particles (10-40 MUm long by 0.1-0.3
      MUm diameter) of the novel [Fe(Htrz)3](CF3SO3)2 complex. The study of the spin
      crossover properties reveals a rare 50 K hysteretic behavior perfectly centered
      at room temperature accompanied by a pronounced thermochromism effect, purple in
      the low spin state and white in the high spin state. 

PMID- 25959769
TI  - Solution-phase dynamic assembly of permanently interlocked aryleneethynylene
      cages through alkyne metathesis.
AB  - Highly stable permanently interlocked aryleneethynylene molecular cages were
      synthesized from simple triyne monomers using dynamic alkyne metathesis. The
      interlocked complexes are predominantly formed in the reaction solution in the
      absence of any recognition motif and were isolated in a pure form using column
      chromatography. This study is the first example of the thermodynamically
      controlled solution-phase synthesis of interlocked organic cages with high
      stability. 

PMID- 25959770
TI  - Schistosomiasis in Egypt: A never-ending story?
AB  - Schistosomiasis has plagued the Egyptian population since the antiquity. The
      disease is still a public health problem in Egypt, despite the tendency of being
      overlooked. In the first part of this review, the past and current trends of
      schistosomiasis in Egypt are reviewed, including history, epidemiology,
      morbidity, therapy, and control of the disease. Most of these aspects are more or
      less relevant to other schistosome-endemic regions all over the world. As only
      one drug is currently available for individual treatment and preventive mass
      chemotherapy, the quest for complementary measures is urgently warranted. Indeed,
      one promising approach is the discovery of a vaccine. Herein, we point out the
      efforts of the Egyptian scientists to develop an efficacious and affordable
      vaccine against schistosomiasis - a step forward in the battle of elimination of
      Schistosoma infection. Based on the candidate vaccine antigens, four types of
      vaccine formulations are discussed: purified antigen vaccines, DNA constructs,
      attenuated cercariae, and excretory-secretory antigen vaccines. Finally, this
      review provides insights into this ancient seemingly long-lasting parasitic
      disease. 

PMID- 25959771
TI  - Pilot study on the combination of an organophosphate-based insecticide paint and
      pyrethroid-treated long lasting nets against pyrethroid resistant malaria vectors
      in Burkina Faso.
AB  - A pilot study to test the efficacy of combining an organophosphate-based
      insecticide paint and pyrethroid-treated Long Lasting Insecticide Treated Nets
      (LLINs) against pyrethroid-resistant malaria vector mosquitoes was performed in a
      real village setting in Burkina Faso. Paint Inesfly 5A IGRTM, comprised of two
      organophosphates (OPs) and an Insect Growth Regulator (IGR), was tested in
      combination with pyrethroid-treated LLINs. Efficacy was assessed in terms of
      mortality for 12 months using Early Morning Collections of malaria vectors and 30
      minute WHO bioassays. Resistance to pyrethroids and OPs was assessed by detecting
      the frequency of L1014F and L1014S kdr mutations and Ace-1(R)G119S mutation,
      respectively. Blood meal origin was identified using a direct enzyme-linked
      immunosorbent assay (ELISA). The combination of Inesfly 5A IGRTM and LLINs was
      effective in killing 99.9-100% of malaria vector populations for 6 months
      regardless of the dose and volume treated. After 12 months, mortality rates
      decreased to 69.5-82.2%. The highest mortality rates observed in houses treated
      with 2 layers of insecticide paint and a larger volume. WHO bioassays supported
      these results: mortalities were 98.8-100% for 6 months and decreased after 12
      months to 81.7-97.0%. Mortality rates in control houses with LLINs were low.
      Collected malaria vectors consisted exclusively of Anopheles coluzzii and were
      resistant to pyrethroids, with a L1014 kdr mutation frequency ranging from 60 to
      98% through the study. About 58% of An. coluzzii collected inside houses had
      bloodfed on non-human animals. Combining Inesfly 5A IGRTM and LLINs yielded a one
      year killing efficacy against An. coluzzii highly resistant to pyrethroids but
      susceptible to OPs that exhibited an anthropo-zoophilic behaviour in the study
      area. The results obtained in a real setting supported previous work performed in
      experimental huts and underscore the need to study the impact that this novel
      strategy may have on clinical malaria and malaria exposure in children in a
      similar area of high pyrethroid resistance in South-Western Burkina Faso. 

PMID- 25959772
TI  - Causes of death in the Taabo health and demographic surveillance system, Cote
      d'Ivoire, from 2009 to 2011.
AB  - BACKGROUND: Current vital statistics from governmental institutions in Cote
      d'Ivoire are incomplete. This problem is particularly notable for remote rural
      areas that have limited access to the health system. OBJECTIVE: To record all
      deaths from 2009 to 2011 and to identify the leading causes of death in the Taabo
      health and demographic surveillance system (HDSS) in south-central Cote d'Ivoire.
      DESIGN: Deaths recorded in the first 3 years of operation of the Taabo HDSS were
      investigated by verbal autopsy (VA), using the InterVA-4 model. InterVA-4 is
      based on the World Health Organization 2012 VA tool in terms of input indicators
      and categories of causes of death. RESULTS: Overall, 948 deaths were recorded, of
      which 236 (24.9%) had incomplete VA data. Among the 712 deaths analyzed,
      communicable diseases represented the leading causes (58.9%), with most deaths
      attributed to malaria (n=129), acute respiratory tract infections (n=110),
      HIV/AIDS (n=80), and pulmonary tuberculosis (n=46). Non-communicable diseases
      accounted for 18.9% of the deaths and included mainly acute abdomen (n=38),
      unspecified cardiac diseases (n=15), and digestive neoplasms (n=13). Maternal and
      neonatal conditions accounted for 8.3% of deaths, primarily pneumonia (n=19) and
      birth asphyxia (n=16) in newborns. Among the 3.8% of deaths linked to trauma and
      injury, the main causes were assault (n=6), accidental drowning (n=4), contact
      with venomous plants/animals (n=4), and traffic-related accidents (n=4). No clear
      causes were determined in 10.0% of the analyzed deaths. CONCLUSIONS: Communicable
      diseases remain the predominant cause of death in rural Cote d'Ivoire. Based on
      these findings, measures are now being implemented in the Taabo HDSS. It will be
      interesting to monitor patterns of mortality and causes of death in the face of
      rapid demographic and epidemiological transitions in this part of West Africa.

PMID- 25959773
TI  - Multivalent Microtubule Recognition by Tubulin Tyrosine Ligase-like Family
      Glutamylases.
AB  - Glutamylation, the most prevalent tubulin posttranslational modification, marks
      stable microtubules and regulates recruitment and activity of microtubule-
      interacting proteins. Nine enzymes of the tubulin tyrosine ligase-like (TTLL)
      family catalyze glutamylation. TTLL7, the most abundant neuronal glutamylase,
      adds glutamates preferentially to the beta-tubulin tail. Coupled with ensemble
      and single-molecule biochemistry, our hybrid X-ray and cryo-electron microscopy
      structure of TTLL7 bound to the microtubule delineates a tripartite microtubule
      recognition strategy. The enzyme uses its core to engage the disordered anionic
      tails of alpha- and beta-tubulin, and a flexible cationic domain to bind the
      microtubule and position itself for beta-tail modification. Furthermore, we
      demonstrate that all single-chain TTLLs with known glutamylase activity utilize a
      cationic microtubule-binding domain analogous to that of TTLL7. Therefore, our
      work reveals the combined use of folded and intrinsically disordered substrate
      recognition elements as the molecular basis for specificity among the enzymes
      primarily responsible for chemically diversifying cellular microtubules. 

PMID- 25959774
TI  - Disruptions of topological chromatin domains cause pathogenic rewiring of gene
      enhancer interactions.
AB  - Mammalian genomes are organized into megabase-scale topologically associated
      domains (TADs). We demonstrate that disruption of TADs can rewire long-range
      regulatory architecture and result in pathogenic phenotypes. We show that
      distinct human limb malformations are caused by deletions, inversions, or
      duplications altering the structure of the TAD-spanning WNT6/IHH/EPHA4/PAX3
      locus. Using CRISPR/Cas genome editing, we generated mice with corresponding
      rearrangements. Both in mouse limb tissue and patient-derived fibroblasts,
      disease-relevant structural changes cause ectopic interactions between promoters
      and non-coding DNA, and a cluster of limb enhancers normally associated with
      Epha4 is misplaced relative to TAD boundaries and drives ectopic limb expression
      of another gene in the locus. This rewiring occurred only if the variant
      disrupted a CTCF-associated boundary domain. Our results demonstrate the
      functional importance of TADs for orchestrating gene expression via genome
      architecture and indicate criteria for predicting the pathogenicity of human
      structural variants, particularly in non-coding regions of the human genome. 

PMID- 25959775
TI  - Co-transcriptional DNA and RNA Cleavage during Type III CRISPR-Cas Immunity.
AB  - Immune systems must recognize and destroy different pathogens that threaten the
      host. CRISPR-Cas immune systems protect prokaryotes from viral and plasmid
      infection utilizing small CRISPR RNAs that are complementary to the invader's
      genome and specify the targets of RNA-guided Cas nucleases. Type III CRISPR-Cas
      immunity requires target transcription, and whereas genetic studies demonstrated
      DNA targeting, in vitro data have shown crRNA-guided RNA cleavage. The molecular
      mechanism behind these disparate activities is not known. Here, we show that
      transcription across the targets of the Staphylococcus epidermidis type III-A
      CRISPR-Cas system results in the cleavage of the target DNA and its transcripts,
      mediated by independent active sites within the Cas10-Csm ribonucleoprotein
      effector complex. Immunity against plasmids and DNA viruses requires DNA, but not
      RNA, cleavage activity. Our studies reveal a highly versatile mechanism of CRISPR
      immunity that can defend microorganisms against diverse DNA and RNA invaders.

PMID- 25959777
TI  - Supramolecular block copolymers by kinetically controlled co-self-assembly of
      planar and core-twisted perylene bisimides.
AB  - New synthetic methodologies for the formation of block copolymers have
      revolutionized polymer science within the last two decades. However, the
      formation of supramolecular block copolymers composed of alternating sequences of
      larger block segments has not been realized yet. Here we show by transmission
      electron microscopy (TEM), 2D NMR and optical spectroscopy that two different
      perylene bisimide dyes bearing either a flat (A) or a twisted (B) core self
      assemble in water into supramolecular block copolymers with an alternating
      sequence of (AmBB)n. The highly defined ultralong nanowire structure of these
      supramolecular copolymers is entirely different from those formed upon self
      assembly of the individual counterparts, that is, stiff nanorods (A) and
      irregular nanoworms (B), respectively. Our studies further reveal that the as
      formed supramolecular block copolymer constitutes a kinetic self-assembly product
      that transforms into thermodynamically more stable self-sorted homopolymers upon
      heating. 

PMID- 25959776
TI  - Viral receptor-binding site antibodies with diverse germline origins.
AB  - Vaccines for rapidly evolving pathogens will confer lasting immunity if they
      elicit antibodies recognizing conserved epitopes, such as a receptor-binding site
      (RBS). From characteristics of an influenza-virus RBS-directed antibody, we
      devised a signature motif to search for similar antibodies. We identified, from
      three vaccinees, over 100 candidates encoded by 11 different VH genes. Crystal
      structures show that antibodies in this class engage the hemagglutinin RBS and
      mimic binding of the receptor, sialic acid, by supplying a critical dipeptide on
      their projecting, heavy-chain third complementarity determining region. They
      share contacts with conserved, receptor-binding residues but contact different
      residues on the RBS periphery, limiting the likelihood of viral escape when
      several such antibodies are present. These data show that related modes of RBS
      recognition can arise from different germline origins and mature through diverse
      affinity maturation pathways. Immunogens focused on an RBS-directed response will
      thus have a broad range of B cell targets. 

PMID- 25959778
TI  - The use of core-shell high-performance liquid chromatography column technology to
      improve biogenic amine quantification in wine.
AB  - BACKGROUND: HPLC column technology has been improved, providing better resolution
      of closely eluting compounds, better analyte sensitivity, and shorter analysis
      times. The core-shell technology columns offer a faster analysis through the use
      of shorter columns without compromising resolution. The aim of this work was to
      improve the methods for determination of biogenic amines (BAs) in wine using the
      new HPLC PFP core-shell column technology. RESULTS: Two different elution
      programs were designed to quantify BAs with the core-shell PFP column. Program I
      flow rate was 2 mL min(-1). The total elution time was 10 min. In elution program
      II, the flow rate was 0.8 mL min(-1) and the total elution time was 25 min. The
      two elution programs used with the core-shell PFP HPLC column showed differences
      related mainly to the histamine peak. The chromatograms showed that when a
      temporary isocratic elution was added in the gradient (program II), the histamine
      peak was eluted later, causing its isolation, and therefore its quantification
      was easier. CONCLUSIONS: Compared to the previous C18 HPLC column for the BAs
      determination in wine, the main advantage of the presented technique is the
      reduction of the run times and solvent volumes, and has a better sensitivity and
      selectivity as peaks are higher and sharper.

PMID- 25959779
TI  - [One-day simultaneous bilateral cataract surgery].
AB  - INTRODUCTION: Effectiveness Evaluation of One-Day Simultaneous Bilateral Cataract
      Surgery (SBCS) Comparing to the Cataract Surgery Performed on Each Eye Separately
      After a Lapse of Time. MATERIAL AND METHODS: The cohort of 100 patients (200
      eyes) consisted of two groups: In the Group1, there were 50 patients (100 eyes)
      who underwent One-day Simultaneous Bilateral Cataract Surgery (SBCS). The Group 2
      consisted 50 patients (100 eyes) who had the surgery on one eye first, and later
      on the fellow eye. The course of the surgery, peroperative and postoperative
      complications were evaluated. The patients from the Group 1 were examined at the
      first postoperative day. In the next course, all patients were examined one week,
      one month, and 3 months after the surgery. In the postoperative phase were,
      besides the complications, the final visual acuity and refraction and its
      deviations from the target refraction followed up. RESULTS: Course of the
      surgery, peroperative and postoperative complications are comparable in both
      groups. Endophthalmitis, or other more serious postoperative complications did
      not appear in either group. Three months after the surgery, the uncorrected
      visual acuity (UCVA) 0.8 and better in the Group 1 had 75 % of patients, and in
      the Group 2 also 75 % of patients. The UCVA 0.5 and better in the Group 1 had 95
      % of patients; in the Group 2 it had 90 % of patients. The best-corrected visual
      acuity 0.8 and better had in both groups 95 % of patients. The final refraction
      after 3 months in the Group 1 was -0.15 +/- 0.91 (-0.12); -3.37; 2.00. In the
      Group 2 the final refraction after 3 months was -0.08 +/- 0.91 (0.00); -3.25;
      2.75. CONCLUSION: The results are showing that both groups of our cohort are
      comparable. The One-Day Simultaneous Bilateral Cataract Surgery (SBCS) is, from
      the surgical point of view, equally safe and effective as classically performed
      cataract surgery.Key words: One-Day Simultaneous Bilateral Cataract Surgery
      (SBCS), refraction, visual acuity, postoperative complications, intraocular
      pressure.

PMID- 25959780
TI  - [Trends in indications of perforating keratoplasty at the Department of
      Ophthalmology, Faculty Hospital, Brno, Czech Republic, E.U., during the period
      2008-2012].
AB  - INTRODUCTION: The aim of the study is retrospective analysis of perforating
      keratoplasty (PKP) indications at the Department of Ophthalmology, Faculty
      Hospital, Masaryk University, Brno, Czech Republic, E.U., during the period of 5
      years, from January 1st, 2008 to December 31st, 2012. MATERIAL AND METHODS: We
      performed the PKP indications retrospective analysis at the Department of
      Ophthalmology, Faculty Hospital, Masaryk University, Brno, Czech Republic, E.U.,
      during the period of 5 years, from January 1st, 2008 to December 31st, 2012, with
      complex evaluation of demographic and clinical data. The clinical diagnoses
      indicating the perforating keratoplasty were divided into 6 groups (keratoconus,
      bulous keratopathy, keratitis, corneal dystrophies, injuries, corneal transplant
      failure, and others) according to Cunningham et al. 2011 (2) and Boimer et al.
      2012(1) methods. RESULTS: Our results correspond to data in the literature
      published abroad, where the majority of recently published papers refer
      significant increase of corneal transplant failure in the last years of follow
      up.Key words: perforating keratoplasty, indications.

PMID- 25959781
TI  - [Dynamic vitreomacular traction].
AB  - PURPOSE: To describe clinical findings in patient with dynamic changes of
      vitreomacular interface and retina. To provide summary of findings about
      mechanism of accommodation and its potential impact on vitreous and retina.
      METHODS: In 57 year old patient we performed comprehensive ophtalmological
      examination including spectral domain optical coherent tomography (SD-OCT). We
      observed the impact of accommodative effort, head-downward position, combination
      of accommodative effort and head-downward position and influence of light reflex
      on vitreomacular interface and retina and change of minimal foveal thickness.
      RESULTS: On SD-OCT we could observe vitreofoveal adhesion on both eyes. During
      accommodative effort in combination with head-downward position we could observe
      symptomatic dynamic vitreomacular traction with temporary elevation of minimal
      foveal thickness. We could not observe impact of only head-downward posture,
      reading with spectacle correction of presbyopia or light reflex on change of
      vitreomacular interface or retina. CONCLUSION: We should suspect dynamic changes
      of vitreomacular interface and retina when we see fluctuating impairment of
      central visual acuity particularly when it is in connection with accommodation
      and head-downward posture.Key words: accommodation, head-downward position,
      vitreomacular interface, SD-OCT.

PMID- 25959782
TI  - [Treatment of pediatric traumatic macular holes].
AB  - PURPOSE: To report the results of treatment of the traumatic macular holes (TMH)
      in four children. METHODS: Retrospective study analyzed data of 4 children, males
      with a mean age of 12.3 years (range, 9-17 years), with diagnosis of TMH. All
      patients suffered a blunt trauma of the eye during the sport activities. The
      symptoms of three patients began after being hit to the face with a soccer balls,
      one boy was hit to his eye by a tennis rocket. Right eyes and left eyes were
      occurred identically. All patients were followed with ophthalmic examination,
      fundus photography and optical coherence tomography (OCT). One patient aged 10
      years two weeks after blunt trauma with a soccer ball achieved spontaneous
      closure of TMH. Three patients aged nine to 17 years with TMH underwent surgical
      repair between September 2007 and May 2012 with three-port vitrectomy. After
      induction of posterior vitreous detachment vitrectomy with or without internal
      limiting membrane (ILM) peeling and gas or silicone oil injection were performed
      followed by prone positioning of head for ten days. Silicon oil was in an only
      patient removed within 3.5 month. RESULTS: All four macular holes were closed
      successfully. Follow-up period was from 10 to 31 month (ranged, 20 month). There
      were no reoperations. There were no surgical complications during follow-up
      period. Visual acuity (VA) improved in all eyes. In spontaneously closed TMH was
      VA improved from 0.5 to 1.0. In surgically treated group VA improved from initial
      0.016 to 0.1 (ranged, 0.061) to final 0.25 to 0.5 (ranged, 0.36). CONCLUSION:
      Pars plana vitrectomy is a safe method for treatment TMH in children without
      tends to spontaneous closure of TMD in OCT imaging. Predisposition for TMH in
      population south-east Asia is suspected.Key words: traumatic macular hole,
      children, optical coherence tomography, vitrectomy, spontaneous closure.

PMID- 25959783
TI  - [Anophthalmic conjunctival sac plastic surgery using the modified cul-de-sac
      method].
AB  - AIM: The author refers about the plastic surgery technique of deepening the
      conjunctival sac in acquired anophthalmos without the orbital implant. The
      condition without the implant was caused primarily or secondarily after the
      enucleation or evisceration. The principal of the cul-de-sac technique is the
      fixation of the lower fornix conjunctiva to the orbital periosteum. MATERIAL AND
      METHODS: The modification of the original surgery technique applied by the author
      is from the nineties of the last century. It consists of the use of long-term
      resorbable suturing material for vascular sutures made from polydiaxonone (PDS 6
      0) and the suture primarily fixated to the orbital periosteum. Only in the second
      phase, the tarsal and bulbar part of the conjunctiva of the lower fornix is
      fixated to the orbital rim. The result is the deepening of the conjunctival sac
      making possible better positioning of the eye prosthesis in the interpalpebral
      fissure from the cosmetic and functional point of view. RESULTS: The author
      presents the successfulness of this surgical technique in six patients operated
      on during the period from 2009 to 2014, presenting photographs of four of them in
      the child and adult age. Shallow of the lower fornix was caused by spontaneous
      elimination of the implant at the school age after the enucleation due to the
      inborn malformation of the eye globe in three years old boy. Extrusion of the
      implants occurred also in two young men after previous enucleation due to the
      malignant intraocular tumors in infant age. In these cases, the influence of the
      growth to the physiognomy of the conjunctival - palpebral area was evident. Among
      included adults were: Eighty-three years old female patient, twelve years after
      the enucleation without the implant due to the endophthalmitis of unknown
      etiology; 62 years old man after the evisceration of the eyeball at the age of
      seven years due to the endophthalmitis after the perforating injury; and 55 years
      old male patient five years after the enucleation of the eye globe with adjacent
      fat tissue removal without implant due to the malignant intraocular tumor with
      the suspicion of its extrascleral growth. Always, the co-incidence of the
      involution process in the conjunctival sac itself took its part. CONCLUSION: The
      surgical technique of deepening the conjunctival sac using the cul-de-sac method
      and using the suturing material made from polydiaxonone (PDS 6-0) may be applied
      in shallow anophthalmic conjunctival sac in the lower fornix. At the same time,
      with this method, the possible ectropion of the lower eyelid is treated as well.
      To prevent the occurrence of the conjunctival sac not suitable for the orbital
      prosthesis application, it should be used the orbital implant during enucleation
      or evisceration surgery.Key words: anophthalmos, plastic surgery of the
      conjunctiva, polydiaxonone.

PMID- 25959784
TI  - [Comparison of visual acuity and higher-order aberrations after standard and
      wavefront-guided myopic femtosecond LASIK].
AB  - PURPOSE: To analyze and compare visual acuity, refractive outcomes and higher
      order aberrations after standard and wavefront-guided Femto-LASIK at 1, 3, and 12
      months postoperatively. METHODS: Study of 95 consecutive eyes of myopic patients
      (-0.5 to -7.0 D), who underwent Femto-LASIK with standard ablation profile (STA)
      (49 eyes) or wavefront-guided ablation (WFG) (46 eyes) using femtosecond laser
      LDV Ziemer and excimer laser MEL 80 Zeiss with iris registration. Primary outcome
      measures were uncorrected distance visual acuity (UDVA), corrected distance
      visual acuity (CDVA), manifest refraction and higher-order ocular aberrations
      (HOAs). HOAs were measured with Hartmann-Shack wavefront aberrometer WASCA, HOAs
      analyzed at 6 mm pupil, assessed total HOAs root mean square (RMS HOAs) and
      individual Zernike coefficients. RESULTS: Preoperatively, there were no
      significant differences between STA and WFG groups in UDVA, CDVA, manifest
      refraction or HOAs. As compared with preoperative values, spherical aberration
      Z(4,0) increased by 0.24 um in both groups and it is the main increasing factor
      of RMS HOAs (0.05 um in STA group and 0.08 um in WFG group). Safety and efficacy
      index is 1.0 in both ablation profiles. Postoperatively, median UDVA and CDVA
      achieved 1.2. No patient lost line of CDVA at 12 month postoperatively. All
      patients were within +/- 0,5 D of emmetropia at 12 months. Significant
      differences were not found between STA and WFG in UDVA, CDVA, manifest refraction
      or HOAs at 1, 3 and 12 month. CONCLUSIONS: Both wavefront-guided and standard
      Femto-LASIK with LDV and MEL 80 platform have shown very good efficacy and
      safety. Myopic Femto-LASIK only slightly increases RMS HOAs, especially by
      induction of spherical aberration. Both methods have equivalent postoperative
      aberration score one year postoperatively.Key words: femtosecond LASIK, higher
      order aberrations, wavefront-guided, visual accuity.

PMID- 25959785
TI  - Effect of Sildenafil on Pre-Eclampsia-Like Mouse Model Induced By L-Name.
AB  - N(omega)-nitro-L-arginine methyl ester (L-NAME) decreases the vasodilator effect
      of nitric oxide (NO) and induces pre-eclampsia in mouse. Sildenafil inhibits the
      degradation of nitric oxide and increases vasodilation. This study aimed to
      determine the effects of sildenafil citrate on angiogenesis and oxidative stress
      at the maternal foetal interface on pre-eclampsia-like mouse model induced by L
      NAME. Twenty pregnant mice were divided into four groups: (i) vehicle control;
      (ii) L-NAME; (iii) sildenafil; (4) L-NAME+sildenafil. L-NAME was administered
      from day 7 of pregnancy and sildenafil from day 8 until day 16; animals were
      euthanized on day 17. Placental and foetal sizes and weights were measured; lipid
      peroxide levels and catalase activity in placental homogenates were determined,
      and placental vascular endothelia were identified by lectin-histochemistry using
      BSA-I lectin. Western blot analysis was used to determine VEGF expression in
      placental homogenates. No changes were seen in placental and foetal development
      in mice with normal pregnancies treated with sildenafil. Treatments with L-NAME
      reduced significantly the placental weight and average height and decreased the
      percentage of the endothelial surface. These alterations may be mediated by the
      reduction of NO levels in trophoblastic cells, due to the inhibitory effect of L
      NAME on nitric oxide synthase (NOS) synthesis. This effect was offset by the
      treatment with sildenafil, with an increase in the percentage of the endothelial
      surface. In conclusion, our results indicate that treatment with sildenafil on
      pre-eclampsia mouse model can be used without adverse effects on the concept and
      its use in the treatment of pre-eclampsia is promising. 

PMID- 25959786
TI  - Levosimendan improves hemodynamic status in critically ill patients with severe
      aortic stenosis and left ventricular dysfunction: an interventional study.
AB  - AIMS: To study the hemodynamic effect of levosimendan administration in acute
      heart failure patients with severe aortic stenosis (AS) and reduced left
      ventricular ejection fraction (LVEF). METHODS: Hemodynamic response to 24 h
      intravenous levosimendan infusion (0.1 MUg/kg/min without a loading dose) in
      patients with severe AS (aortic valve area <=1 cm(2) , time-velocity integral
      between left ventricular out-flow tract and aortic valve <0.25), reduced LVEF
      (<=40%), and a depressed cardiac index (CI) <2.2 L/min/m(2) was determined in a
      sequential group of nine patients aged 76 +/- 10 years (5 men). RESULTS: Baseline
      mean ejection fraction was 33 +/- 0.7%; mean aortic valve area was 0.37 +/-0.11
      cm(2) /m(2) ; peak and mean gradients of 63.6 +/- 20.53 and 36.7 +/- 12.62 mmHg,
      respectively; and mean CI was 1.65 +/- 0.20 L/min/m(2) . At 6 and 12 h of
      levosimendan therapy, mean CI had increased to 2.00 +/- 0.41 L/min/m(2) (P =
      0.02) and 2.17 +/- 0.40 L/min/m(2) (P = 0.01), respectively. At 24 h, mean CI had
      increased further to 2.37 +/- 0.49 L/min/m(2) (P = 0.01). A significant
      beneficial effect was also observed in pulmonary capillary wedge pressure,
      pulmonary artery mean pressure, central venous pressure, systemic vascular
      resistances, pulmonary vascular resistances, stroke volume index, left
      ventricular stroke work index. NTproBNP levels decreased at 24 h of levosimendan
      treatment. Levosimendan infusion was also well tolerated. Five patients
      subsequently underwent aortic valve surgery replacement. One died (of
      postoperative multiorgan failure). At 30 days, overall survival was 75%.
      CONCLUSIONS: Levosimendan administration improves hemodynamic parameters in
      critically ill patients with severe AS and reduced LVEF. In our study, it
      provides a safe and effective bridge to aortic-valve replacement or oral
      vasodilator therapy in surgical contraindicated patients. A controlled study is
      needed to confirm these preliminary findings.

PMID- 25959787
TI  - A meta-analysis of mammographic screening with and without clinical breast
      examination.
AB  - Mammographic screening with clinical breast examination has been recommended in
      Japan since 2000. Although mammographic screening without clinical breast
      examination has not been recommended, its introduction is anticipated. The
      efficacies of mammographic screening with and without clinical breast examination
      were evaluated based on the results of randomized controlled trials. PubMed and
      other databases for studies published between 1985 and 2014 were searched. The
      study design was limited to randomized controlled trials to evaluate mortality
      reduction from breast cancer. Five studies were eligible for meta-analysis of
      mammographic screening without clinical breast examination. The relative risk for
      women aged 40-74 years was 0.75 (95% confidence interval, 0.67-0.83). Three
      studies evaluated the efficacy of mammographic screening with clinical breast
      examination. The relative risk for women aged 40-64 years was 0.87 (95%
      confidence interval, 0.77-0.98). The number needed to invite was always lower in
      mammographic screening without clinical breast examination than in mammographic
      screening with clinical breast examination. In both screening methods, the number
      needed to invite was higher in women aged 40-49 years than in women aged 50-70
      years. These results suggest that mammographic screening without clinical breast
      examination can afford higher benefits to women aged 50 years and over. Although
      evidence of the efficacy of mammographic screening without clinical breast
      examination was confirmed based on the results of the randomized controlled
      trials, a Japanese study is needed to resolve local problems.

PMID- 25959788
TI  - Association between hemoglobin A1c variability and subclinical coronary
      atherosclerosis in subjects with type 2 diabetes.
AB  - AIMS: We examined the association between hemoglobin A1c (HbA1c) variability and
      subclinical coronary atherosclerosis in subjects with type 2 diabetes. METHODS:
      We used the multidetector coronary computed tomography data collected from
      subjects with type 2 diabetes who did not have a history of cardiovascular
      disease or angina symptoms. HbA1c measurements preceding the date of cardiac
      imaging were retrospectively collected, and intraindividual SD (HbA1c-SD), CV and
      adjusted SD of HbA1c measurements were calculated. Subclinical coronary
      atherosclerosis was defined as calcium score >400 without any cardiac symptoms.
      RESULTS: A total of 595 subjects were categorized according to the median value
      of each HbA1c variability indicators. The prevalence of subclinical coronary
      atherosclerosis was higher in higher HbA1c variability group compared with lower
      HbA1c variability group. Multivariable logistic regression analysis showed that
      higher HbA1c-SD and -CV were associated with the presence of subclinical coronary
      atherosclerosis, independent of mean HbA1c level in subjects with diabetes
      duration <=10 years (OR [95% CI]; HbA1c-SD, 2.894 [1.105-7.584]; HbA1c-CV, 2.540
      [1.022-6.316]). CONCLUSIONS: Long-term stabilization of blood glucose level might
      be important in preventing subclinical coronary atherosclerosis in subjects with
      earlier period of type 2 diabetes.

PMID- 25959789
TI  - Association of the G1057D polymorphism in insulin receptor substrate 2 gene with
      type 2 diabetes mellitus: a meta-analysis.
AB  - OBJECTIVES: The G1057D polymorphism in insulin receptor substrate (IRS)-2 gene is
      associated with type 2 diabetes mellitus (T2DM) risk, but results in published
      literatures are controversial. In addition, the effect of obesity as a modifier
      on this association is also inconsistent. Thus, this meta-analysis was performed
      to assess the above-mentioned association. METHODS: A comprehensive search was
      performed to identify case-control or cohort studies (from 1990 to 2014) of the
      aforementioned association. The I(2) statistic was used to examine between-study
      heterogeneity. Fixed or random effect model was selected based on heterogeneity
      test among studies. Publication bias was estimated using modified Egger's
      regression test. RESULTS: Nine articles with ten studies were included. After
      excluding studies deviated from Hardy-Weinberg equilibrium (HWE) in controls,
      results showed a significant association of D allele with reduced T2DM risk in
      dominant (OR = 0.825, 95% CI: 0.705-0.965) and codominant (OR = 0.857, 95% CI:
      0.763-0.964) models, but no significant association in recessive (OR = 0.806, 95%
      CI: 0.628-1.035) model. For studies stratified by obesity, after excluding
      studies deviated from HWE in controls, no significant association of D allele
      with T2DM risk was found in three inherited models in obese group; however, a
      significant protective effect of D allele was observed in dominant (OR = 0.714,
      95% CI: 0.533-0.958), recessive (OR = 0.438, 95% CI: 0.253-0.760) and codominant
      (OR = 0.706, 95% CI: 0.565-0.883) models in non-obese group. CONCLUSIONS: This
      meta-analysis suggested that D allele of G1057D polymorphism have a significant
      effect on reduced risk of T2DM, and obesity is a modifier of this association.
      This result needs to be confirmed by further studies.

PMID- 25959790
TI  - Four-pole galvanic vestibular stimulation causes body sway about three axes.
AB  - Galvanic vestibular stimulation (GVS) can be applied to induce the feeling of
      directional virtual head motion by stimulating the vestibular organs
      electrically. Conventional studies used a two-pole GVS, in which electrodes are
      placed behind each ear, or a three-pole GVS, in which an additional electrode is
      placed on the forehead. These stimulation methods can be used to induce virtual
      head roll and pitch motions when a subject is looking upright. Here, we proved
      our hypothesis that there are current paths between the forehead and mastoids in
      the head and show that our invented GVS system using four electrodes succeeded in
      inducing directional virtual head motion around three perpendicular axes
      containing yaw rotation by applying different current patterns. Our novel method
      produced subjective virtual head yaw motions and evoked yaw rotational body sway
      in participants. These results support the existence of three isolated current
      paths located between the mastoids, and between the left and right mastoids and
      the forehead. Our findings show that by using these current paths, the generation
      of an additional virtual head yaw motion is possible. 

PMID- 25959791
TI  - Towards a functional atlas of human white matter.
AB  - OBJECTIVES: Although diffusion tensor imaging (DTI) and postmortem dissections
      improved the knowledge of white matter (WM) anatomy, functional information is
      lacking. Our aims are: to provide a subcortical atlas of human brain functions;
      to elucidate the functional roles of different bundles; to provide a
      probabilistic resection map of WM. EXPERIMENTAL DESIGN: We studied 130 patients
      who underwent awake surgery for gliomas (82 left; 48 right) with
      electrostimulation mapping at cortical and subcortical levels. Different aspects
      of language, sensori-motor, spatial cognition, and visual functions were
      monitored. 339 regions of interest (ROIs) including the functional response
      errors collected during stimulation were co-registered in the MNI space, as well
      as the resections' areas and residual tumors. Functional response errors and
      resection areas were matched with DTI and cortical atlases. Subcortical maps for
      each function and a probability map of resection were computed. PRINCIPAL
      OBSERVATIONS: The medial part of dorsal stream (arcuate fasciculus) subserves
      phonological processing; its lateral part [indirect anterior portion of the
      superior longitudinal fascicle (SLF)] subserves speech planning. The ventral
      stream subserves language semantics and matches with the inferior fronto
      occipital fascicle. Reading deficits match with the inferior longitudinal
      fascicle. Anomias match with the indirect posterior portion of the SLF. Frontal
      WM underpins motor planning and execution. Right parietal WM subserves spatial
      cognition. Sensori-motor and visual fibers were the most preserved bundles.
      CONCLUSIONS: We report the first anatomo-functional atlas of WM connectivity in
      humans by correlating cognitive data, electrostimulation, and DTI. We provide a
      valuable tool for cognitive neurosciences and clinical applications.

PMID- 25959792
TI  - Risks and outcomes of spinal deformity surgery in Chiari malformation, Type 1,
      with syringomyelia versus adolescent idiopathic scoliosis.
AB  - BACKGROUND CONTEXT: Chiari malformation, Type 1, with syringomyelia (CIM+SM) is
      often associated with spinal deformity. The safety of scoliosis surgery this
      population is controversial and has never been directly compared with adolescent
      idiopathic scoliosis (AIS). PURPOSE: The purpose of this study was to compare the
      safety and subjective outcomes of spinal deformity surgery between patients with
      Chiari malformation Type 1-associated scoliosis and a matched AIS cohort. STUDY
      DESIGN: This study is based on a retrospective matched cohort analysis. PATIENT
      SAMPLE: Patients with CIM+SM and treated with spinal fusion for spinal deformity
      were identified in the surgical records of a single institution and were matched,
      1:1, with AIS patients undergoing spinal fusion at the same institution. OUTCOME
      MEASURES: The outcome measures were neurological monitoring data quality and
      integrity, radiographic parameters, and Scoliosis Research Society Questionnaire
      22 (SRS-22) scores. METHODS: A clinical database was reviewed for patients
      undergoing spinal reconstruction for CIM+SM-associated spinal deformity at our
      institution from 2000 to 2012. Thirty-six CIM+SM patients were identified and
      matched to an AIS cohort (1:1) based on age, gender, major curve magnitude,
      fusion length, and revision status. Demographics, deformity morphology, surgical
      details, neuromonitoring data, and preoperative and postoperative SRS-22 scores
      were recorded at a minimum of 2-year follow-up. Changes in SRS-22 scores were
      compared within and between groups. Complications and neurological monitoring
      data issues were compared between groups. RESULTS: Mean age was 14.5+/-5 years
      (CIM+SM: 14.6+/-5; AIS: 14.4+/-5), and 42% of patients were male. Preoperative
      mean major coronal Cobb measured 58 degrees +/-25 degrees  versus 57 degrees +/
      17 degrees  (p=.84) with mean kyphosis 52 degrees +/-17 degrees  versus 41
      degrees +/-20 degrees  (p=.018). An average of 10.4+/-2.6 vertebral levels were
      fused (10.4+/-2.8 vs. 10.4+/-2.3, p=.928). No differences existed in surgical
      approach (p=.336), estimated blood loss (680+/-720 vs. 660+/-310 mL, p=.845), or
      duration of surgery (6.0+/-2.2 vs. 5.6+/-2 hours, p=.434). Complication rate was
      comparable between the two groups (33% vs. 14%, p=.052). Chiari malformation,
      Type 1, with syringomyelia experienced more neurological complications (11% vs.
      0%, p=.04) and neuromonitoring difficulties (28% vs. 3%, p=.007) than the AIS
      cohort. Mean curve correction was comparable at 2 years (58% CIM+SM vs. 64% AIS,
      p=.2). At follow-up, both CIM+SM and AIS groups demonstrated improved cumulative
      SRS-22 outcome subscores (CIM+SM: +0.4, p=.027; AIS: +0.3, p<.001). No difference
      in outcome subscores existed between CIM+SM and AIS groups. CONCLUSIONS: Although
      CIM+SM patients undergoing spine reconstruction can expect similar deformity
      corrections and outcome scores to AIS patients, they also experience higher rates
      of neuromonitoring difficulties and neurological complications related to
      surgery. Surgeons should be prepared for these difficulties, particularly in
      children with larger syrinx size.

PMID- 25959793
TI  - Oncogenes create a unique landscape of fragile sites.
AB  - Recurrent genomic instability in cancer is attributed to positive selection
      and/or the sensitivity of specific genomic regions to breakage. Among these
      regions are fragile sites (FSs), genomic regions sensitive to replication stress
      conditions induced by the DNA polymerase inhibitor aphidicolin. However, the
      basis for the majority of cancer genomic instability hotspots remains unclear.
      Aberrant oncogene expression induces replication stress, leading to DNA breaks
      and genomic instability. Here we map the cytogenetic locations of oncogene
      induced FSs and show that in the same cells, each oncogene creates a unique
      fragility landscape that only partially overlaps with aphidicolin-induced FSs.
      Oncogene-induced FSs colocalize with cancer breakpoints and large genes, similar
      to aphidicolin-induced FSs. The observed plasticity in the fragility landscape of
      the same cell type following oncogene expression highlights an additional level
      of complexity in the molecular basis for recurrent fragility in cancer. 

PMID- 25959794
TI  - Evaluation of Yogurt Microstructure Using Confocal Laser Scanning Microscopy and
      Image Analysis.
AB  - The microstructure of protein networks in yogurts defines important physical
      properties of the yogurt and hereby partly its quality. Imaging this protein
      network using confocal scanning laser microscopy (CSLM) has shown good results,
      and CSLM has become a standard measuring technique for fermented dairy products.
      When studying such networks, hundreds of images can be obtained, and here image
      analysis methods are essential for using the images in statistical analysis.
      Previously, methods including gray level co-occurrence matrix analysis and
      fractal analysis have been used with success. However, a range of other image
      texture characterization methods exists. These methods describe an image by a
      frequency distribution of predefined image features (denoted textons). Our
      contribution is an investigation of the choice of image analysis methods by
      performing a comparative study of 7 major approaches to image texture
      description. Here, CSLM images from a yogurt fermentation study are investigated,
      where production factors including fat content, protein content, heat treatment,
      and incubation temperature are varied. The descriptors are evaluated through
      nearest neighbor classification, variance analysis, and cluster analysis. Our
      investigation suggests that the texton-based descriptors provide a fuller
      description of the images compared to gray-level co-occurrence matrix descriptors
      and fractal analysis, while still being as applicable and in some cases as easy
      to tune. 

PMID- 25959795
TI  - Calreticulin mutation profile in Indian patients with primary myelofibrosis.
AB  - INTRODUCTION: Somatic mutations in Calreticulin (CALR) have been recently
      discovered in JAK2/MPL unmutated patients with primary myelofibrosis (PMF) or
      essential thrombocythemia. METHODS: Clinical and hematologic features were
      obtained for 80 patients with PMF. JAK2V617F mutation was analyzed by DNA tetra
      primer amplification refractory mutation system (ARMS-PCR). CALR and MPL
      mutations were identified by bi-directional Sanger sequencing. RESULTS: CALR
      mutations were detected in 11.2% (9/80) of all PMF patients and 25.7% (9/35) of
      all JAK2V617F and MPL unmutated patients all of which were Type I mutation or
      deletions. A novel CALR mutation pattern (c.1241_1288del) was identified in one
      (1/9) patient. No case of Type II mutations or scattered point mutations was
      found in any of these patients. Uni-variate analysis at presentation showed that
      CALR mutations were significantly associated with younger age (P = 0.003) and
      larger spleen size (P = 0.001). No significant correlation was found between CALR
      mutation and clinico-hematologic characteristics or international prognostic
      scoring system (IPSS) scoring of the PMF patients. CONCLUSION: CALR mutations
      have a distinct molecular profile in Indian patients, different from that of
      other studies worldwide. Larger prospective studies need to be designed to
      establish the impact of paucity of Type II mutations in contributing to disease
      phenotype and prognostic outcome of patients.

PMID- 25959796
TI  - Reduction of interleukin-10 production by B cells in intractable toxic epidermal
      necrolysis.
AB  - Several interleukin (IL)-10 producing B-cell subsets have been identified
      recently. However, few studies have examined the role of them in toxic epidermal
      necrolysis (TEN). We describe a 41-year-old woman with TEN who had B-cell
      lymphoma and a history of treatments including B-cell depletion therapy. Her re
      epithelization was still ongoing after 7 months, despite treatments. To
      investigate her immune system, we compared cytokine and chemokine production from
      B cells and non-B cells isolated from the patient and another non-lymphoma TEN
      patient. IL-10 production from B cells decreased in the patient compared with the
      control TEN-only patient. Cytokine and chemokine levels from non-B cells involved
      in inflammation were elevated in the patient compared with the control patient.
      In conclusion, this study demonstrates that IL-10 from B cells as well as
      regulatory T cells is critical in the pathogenesis of TEN, and that B-cell
      dysfunction based on B-cell lymphoma and B-cell depletion therapy may be involved
      in the intractability of TEN. 

PMID- 25959797
TI  - Features of a new full length HLA allele: A*02:455.
AB  - The full length sequence of HLA-A*02:455 differs from HLA-A*02:01:01:01 by one
      amino acid substitution: A245E. 

PMID- 25959798
TI  - Nanoprobes for enhanced electrochemical DNA sensors.
AB  - Biosensors, small devices enabling selective bioanalysis because of properly
      assembled biological recognition molecules, represent the fortuitous results of
      years of interdisciplinary and complementary investigations in different fields
      of science. The ultimate role of a biosensor is to provide coupling between the
      recognition element and the analyte of interest, bringing a quantitative value of
      its concentrations into a complex sample matrix. They offer many advantages.
      Among them, portability, low cost with fast response times, and the possibility
      to operate in situ without the need for sample preparation are certainly the most
      important. Among biosensors, a large space is occupied by DNA biosensors.
      Screening genomic DNA is of fundamental importance for the development of new
      tools available to physicians during the clinical process. Sequencing of
      individual human genomes, accomplished principally by microarrays with optical
      detection, is complex and expensive for current clinical protocols. Efforts in
      research are focused on simplifying and reducing the cost of DNA biosensors. For
      this purpose, other transduction techniques are under study to make more portable
      and affordable DNA biosensors. Compared with traditional optical detection tools,
      electrochemical methods allow the same sensitivity and specificity but are less
      expensive and less labor intensive. Scalability of electrochemical devices makes
      it possible to use the advantages introduced by nanosized components. The
      involvement of nanomaterials and nanostructures with custom-tailored shapes and
      properties is expected to rapidly boost the field of electrochemical DNA
      biosensors and, in general, that of next-generation sequencing technologies.

PMID- 25959799
TI  - Evaluation of a PCR/ESI-MS platform to identify respiratory viruses from
      nasopharyngeal aspirates.
AB  - Acute respiratory tract infection is a major cause of morbidity and mortality
      worldwide, particularly in infants and young children. High-throughput, accurate,
      broad-range tools for etiologic diagnosis are critical for effective epidemic
      control. In this study, the diagnostic capacities of an Ibis platform based on
      the PCR/ESI-MS assay were evaluated using clinical samples. Nasopharyngeal
      aspirates (NPAs) were collected from 120 children (<5 years old) who were
      hospitalized with lower respiratory tract infections between November 2010 and
      October 2011. The respiratory virus detection assay was performed using the
      PCR/ESI-MS assay and the DFA. The discordant PCR/ESI-MS and DFA results were
      resolved with RT-PCR plus sequencing. The overall agreement for PCR/ESI-MS and
      DFA was 98.3% (118/120). Compared with the results from DFA, the sensitivity and
      specificity of the PCR/ESI-MS assay were 100% and 97.5%, respectively. The
      PCR/ESI-MS assay also detected more multiple virus infections and revealed more
      detailed subtype information than DFA. Among the 12 original specimens with
      discordant results between PCR/ESI-MS and DFA, 11 had confirmed PCR/ESI-MS
      results. Thus, the PCR/ESI-MS assay is a high-throughput, sensitive, specific and
      promising method to detect and subtype conventional viruses in respiratory tract
      infections and allows rapid identification of mixed pathogens.

PMID- 25959800
TI  - BioBankWarden: A web-based system to support translational cancer research by
      managing clinical and biomaterial data.
AB  - BACKGROUND: Researchers of translational medicine face numerous challenges in
      attempting to bring research results to the bedside. This field of research
      covers a wide range of resources, including blood and tissue samples, which are
      processed for isolation of RNA and DNA to study cancer omics data (genomics,
      proteomics and metabolomics). Clinical information about patients' habits, family
      history, physical examinations, remissions, etc., is also important to underpin
      studies aimed at identifying patterns that lead to the development of cancer and
      to its successful treatment. PURPOSE: Development of a web-based computer system
      BioBankWarden-to manage, consolidate and integrate these diversified data,
      enabling cancer research groups to retrieve and analyze clinical and biomolecular
      data within an integrative environment. The system has a three-tier architecture
      comprising database, logic and user-interface layers. RESULTS: The system's
      integrated database and user-friendly interface allow for the control of patient
      records, biomaterial storage, research groups, research projects, users and
      biomaterial exchange. CONCLUSIONS: BioBankWarden can be used to store and
      retrieve specific information from different clinical fields linked to
      biomaterials collected from patients, providing the functionalities required to
      support translational research in the field of cancer.

PMID- 25959801
TI  - Estrogen suppresses melatonin-enhanced hyperactivation of hamster spermatozoa.
AB  - Hamster sperm hyperactivation is enhanced by progesterone, and this progesterone
      enhanced hyperactivation is suppressed by 17beta-estradiol (17betaE2) and gamma
      aminobutyric acid (GABA). Although it has been indicated that melatonin also
      enhances hyperactivation, it is unknown whether melatonin-enhanced
      hyperactivation is also suppressed by 17betaE2 and GABA. In the present study,
      melatonin-enhanced hyperactivation was significantly suppressed by 17betaE2 but
      not by GABA. Moreover, suppression of melatonin-enhanced hyperactivation by
      17betaE2 occurred through non-genomic regulation via the estrogen receptor (ER).
      These results suggest that enhancement of hyperactivation is regulated by
      melatonin and 17betaE2 through non-genomic regulation. 

PMID- 25959803
TI  - Collaboration: what does it really mean to nurses?

PMID- 25959802
TI  - The CDKN1B-RB1-E2F1 pathway protects mouse spermatogonial stem cells from genomic
      damage.
AB  - Spermatogonial stem cells (SSCs) undergo self-renewal divisions to provide the
      foundation for spermatogenesis. Although Rb1 deficiency is reportedly essential
      for SSC self-renewal, its mechanism has remained unknown. Here we report that Rb1
      is critical for cell cycle progression and protection of SSCs from DNA double
      strand breaks (DSBs). Cultured SSCs depleted of Cdkn1b proliferated poorly and
      showed diminished expression of CDK4 and RB1, thereby leading to
      hypophosphorylation of RB1. Rb1 deficiency induced cell cycle arrest and
      apoptosis in cultured SSCs, which expressed markers for DNA DSBs. This DNA damage
      is caused by increased E2F1 activity, the depletion of which decreased DNA DSBs
      caused by Rb1 deficiency. Depletion of Cdkn1a and Bbc3, which were upregulated by
      Trp53, rescued Rb1-deficient cells from undergoing cell cycle arrest and
      apoptosis. These results suggest that the CDKN1B-RB1-E2F1 pathway is essential
      for SSC self-renewal and protects SSCs against genomic damage. 

PMID- 25959804
TI  - Effect of PALB2 status on breast cancer precision medicine.

PMID- 25959805
TI  - Clinical outcomes in women with breast cancer and a PALB2 mutation: a prospective
      cohort analysis.
AB  - BACKGROUND: Mutations in PALB2 predispose to breast cancer, but the effect on
      prognosis of carrying a PALB2 mutation has not been ascertained. We aimed to
      estimate the odds ratio for breast cancer in women with an inherited mutation in
      PALB2 and 10-year survival after breast cancer in patients who carry a PALB2
      mutation. METHODS: Between 1996 and 2012, patients with invasive breast cancer
      were recruited prospectively from 18 hospitals in Poland and genotyped for two
      deleterious mutations in PALB2 (509_510delGA and 172_175delTTGT). A control group
      of 4702 women without cancer was recruited for comparison. The primary endpoint
      was death from any cause, as determined by medical records from the Polish
      Ministry of the Interior and Administration. In patients with breast cancer, 10
      year survival of carriers of a PALB2 mutation was calculated and compared with
      that of non-carriers. FINDINGS: 17 900 women with breast cancer were invited to
      participate, of whom 12 529 were genotyped successfully. A PALB2 mutation was
      present in 116 (0.93%, 95% CI 0.76-1.09) of 12 529 patients and in ten (0.21%,
      0.08-0.34) of 4702 controls (odds ratio 4.39, 95% CI 2.30-8.37; p<0.0001). 10
      year survival for women with breast cancer and a PALB2 mutation was 48.0% (95% CI
      36.5-63.2), compared with 74.7% (73.5-75.8) for patients with breast cancer
      without a mutation (adjusted hazard ratio for death 2.27, 95% CI 1.64-3.15;
      p<0.0001). INTERPRETATION: Women with a PALB2 mutation face an increased risk of
      breast cancer and might be at a higher risk of death from breast cancer compared
      with non-carriers. Increased surveillance should be offered to unaffected women
      who carry a PALB2 mutation. FUNDING: Polish National Science Centre.

PMID- 25959806
TI  - Parenthood in adult female survivors treated for Hodgkin's lymphoma during
      childhood and adolescence: a prospective, longitudinal study.
AB  - BACKGROUND: Little is known about parenthood in women who were treated for
      Hodgkin's lymphoma during childhood and adolescence. We aimed to assess the
      frequency of parenthood in female survivors of Hodgkin's lymphoma younger than 18
      years at diagnosis, and to compare it with that in a female population control
      group. METHODS: In this prospective, longitudinal study, our cohort consisted of
      590 female patients younger than 18 years at diagnosis who participated in one of
      five Hodgkin's lymphoma treatment studies between June 19, 1978, and July 12,
      1995. Women who had been followed up for 5 years or longer, were in continuous
      complete remission, and had no second malignancy or Hodgkin's lymphoma relapse
      before parenthood were included in our parenthood analysis. Parenthood was
      defined as the delivery of a liveborn child. Frequency of parenthood was compared
      with that in the German female population aged 16-49 years, using data from the
      2012 Mikrozensus population survey. We assessed parenthood by estimating
      cumulative incidences and hazard ratios (HRs) with associated variables.
      FINDINGS: 467 of 590 patients in our cohort had long-term follow-up (median 20.4
      years [IQR 16.3-24.8]) and were in continuous complete remission. 228 (49%) of
      467 patients had 406 children (median of 1.78 children per mother, range 1-7).
      Cumulative incidences of parenthood were 67% (95% CI 64-75) at 27.7 years of
      follow-up (the longest number of years that a patient was followed up before she
      had her first child) and 69% (61-74) at 39.8 years of age (the oldest age of a
      patient before she had her first child). The incidence of parenthood did not
      differ between our cohort and the female German population for any age group up
      to 49 years, except for the 66 women aged 40-44 years at the time of last
      information, who had a significantly lower frequency of parenthood compared with
      the general population (40 [61%] of 66 vs 2,208,000 [78%] of 2,847,000; p=0.001).
      Procarbazine in cumulative doses up to 11,400 mg/m(2), cyclophosphamide in
      cumulative doses up to 6000 mg/m(2), alkylating agent dose scores of 1-5, therapy
      group based on disease stage at diagnosis, abdominal and supradiaphragmatic
      radiation, and age at treatment had no significant or only minor effects on
      parenthood. Parenthood was significantly reduced in survivors receiving pelvic
      radiation compared with those who received abdominal and supradiaphragmatic
      radiation (HR 0.76, 95% CI 0.61-0.95; p=0.01). INTERPRETATION: The results of
      this study document an overall favourable prognosis for parenthood in female
      survivors of Hodgkin's lymphoma. They will assist counselling of female survivors
      about their positive potential for future parenthood. FUNDING: Deutsche
      Kinderkrebsstiftung, Jens-Brunken-Stiftung fur Leukamie und Lymphomforschung, and
      Kinderkrebshilfe Munster.

PMID- 25959807
TI  - Plasma soluble vascular adhesion protein-1 concentration correlates with arterial
      stiffness: A cross-sectional study.
AB  - BACKGROUND: Arterial stiffness is related to inflammation, oxidative stress,
      advanced glycation end products (AGEs), and endothelial dysfunction. Vascular
      adhesion protein-1 (VAP-1) is both as an adhesion molecule involving in
      inflammation and as an amine oxidase producing aldehyde and hydrogen peroxide
      involved in protein cross-linking, oxidative stress and endothelial injury.
      OBJECTIVE: We explored the associations of plasma soluble VAP-1 (sVAP-1) with
      arterial stiffness. DESIGN: Cross-sectional study. SETTING: Health Examination
      Center at the General Hospital of the Air Force in Beijing, China. SUBJECTS: 568
      Han Chinese healthy persons living in Beijing (aged 50.7 +/- 8.0 years). METHODS:
      sVAP-1 concentration was assessed by enzyme-linked immunosorbent assay. Arterial
      stiffness was measured as brachial-ankle pulse wave velocity (baPWV) on both left
      and right sides of the examinees, and the larger and the mean values were
      recorded. Cardiovascular risk factors were investigated. RESULTS: sVAP-1 was
      significantly associated with maximal or mean baPWV in subjects of age >= 60
      years after adjusting for baPWV-related confounders (beta=36.922, p<0.05 or
      beta=32.512, p<0.05) or after adjusting for all the variables (beta=37.924,
      p<0.05 or beta=33.193, p<0.05), but not in subjects of age <60 years. sVAP-1 had
      an independent and positive correlation with age (r=0.222, p<0.001). CONCLUSIONS:
      Plasma sVAP-1, increased with age, is associated with arterial stiffness in older
      individuals. VAP-1 may be important mechanism for vascular aging.

PMID- 25959808
TI  - Dispersibility-Dependent Biodegradation of Graphene Oxide by Myeloperoxidase.
AB  - Understanding human health risk associated with the rapidly emerging graphene
      based nanomaterials represents a great challenge because of the diversity of
      applications and the wide range of possible ways of exposure to this type of
      materials. Herein, the biodegradation of graphene oxide (GO) sheets is reported
      by using myeloperoxidase (hMPO) derived from human neutrophils in the presence of
      a low concentration of hydrogen peroxide. The degradation capability of the
      enzyme on three different GO samples containing different degree of oxidation on
      their graphenic lattice, leading to a variable dispersibility in aqueous media is
      compared. hMPO fails in degrading the most aggregated GO, but succeeds to
      completely metabolize highly dispersed GO samples. The spectroscopy and
      microscopy analyses provide unambiguous evidence for the key roles played by
      hydrophilicity, negative surface charge, and colloidal stability of the aqueous
      GO in their biodegradation by hMPO catalysis. 

PMID- 25959809
TI  - Psychosocial approaches to violence and aggression: contextually anchored and
      trauma-informed interventions.
AB  - Psychosocial interventions are part of the complex understanding and treatment of
      violent behavior in our state mental health hospitals. A comprehensive assessment
      of violence and aggression includes attention to all 3 domains of prevention and
      assessment (primary-institutional, secondary-structural, and tertiary-direct).
      Trauma experiences and their consequences may include behavioral violence and
      aggression. The authors' premise is that trauma is a universal component in the
      individual assessment of violent behavior. Therapeutic interventions must include
      a trauma-informed formulation to be effective. Organizational commitment to
      trauma-informed, person-centered, recovery-oriented (TPR) care is crucial to the
      efficacy of any of the interventions discussed. Thus, the dynamic nature of the
      individual, interpersonal, environmental, and cultural factors associated with
      the daily operations of the inpatient unit need to be assessed through the lens
      of primary and secondary violence prevention, building on the recognition that
      the majority of persons served and staff have significant trauma histories. Once
      a compassionate, respectful, empathic, and empowering approach is embraced by
      leadership and staff, the work with individuals can proceed more effectively.
      Interventions used include a variety of cognitive-behavioral, interpersonal, and
      somatosensory therapies. These interventions, when effectively applied, result in
      more self-esteem, self-mastery, self-control for the person served, and
      diminished behavioral violence. 

PMID- 25959810
TI  - Vitamins A and D have antagonistic effects on expression of effector cytokines
      and gut-homing integrin in human innate lymphoid cells.
AB  - BACKGROUND: Retinoic acid (RA), the main biologically active metabolite of
      vitamin A, is known to promote gut homing of lymphocytes, as well as various
      regulatory and effector immune responses. In contrast, the active form of vitamin
      D, 1,25-dihydroxyvitamin D3 (1,25D3), is predominantly immunosuppressive. Little
      is known about the direct effects of these vitamins on the recently identified
      innate lymphoid cells (ILCs). OBJECTIVE: We sought to characterize the effects of
      RA and 1,25D3 on human ILCs. METHODS: Peripheral blood mononuclear cells were
      isolated from 27 non-selected blood donor buffy coats, and ILCs were sorted by
      FACS. ILC1, ILC2, and ILC3 cells were cultured for 5 days with RA, 1,25D3, and
      various cytokines known to activate ILCs (IL-2, IL-7, IL-12, thymic stromal
      lymphopoietin (TSLP), IL-25, and IL-33). Cytokines produced by ILCs were measured
      in culture supernatants, and surface receptor expression was analysed by flow
      cytometry. RESULTS: Retinoic acid acted synergistically with IL-2 and other
      activating cytokines to induce expression of the gut-homing integrin alpha4beta7
      in ILCs, as well as production of IL-5 and IL-13 in ILC2 cells, and IFN-gamma in
      ILC1 and ILC3 cells. Expression of integrin alpha4beta7 and cytokine production
      in ILCs stimulated with RA + IL-2 was increased at least fourfold as compared to
      ILCs cultured with RA or IL-2 alone. In contrast, RA completely inhibited the IL
      2-induced expression of cutaneous lymphocyte antigen (CLA) in ILCs. Moreover,
      addition of 1,25D3 to ILCs cultured with RA + IL-2 inhibited cytokine production
      and expression of integrin alpha4beta7 by at least 30%. CONCLUSIONS: Retinoic
      acid and 1,25D3 have antagonistic effects on the expression of effector cytokines
      and gut-homing integrin by human ILCs. The balance between these vitamins may be
      an important factor in the functioning of ILCs and the diseases in which ILCs are
      implicated, such as allergic inflammation.

PMID- 25959811
TI  - Cardamonin induces autophagy and an antiproliferative effect through JNK
      activation in human colorectal carcinoma HCT116 cells.
AB  - Cardamonin (2',4'-dihydroxy-6'-methoxychalcone) is derived from Alpinia
      katsumadai Hayata (Zingiberaceae), a plant that has been used in Traditional
      Chinese Medicine for thousands of years. Several anticancer agents have been
      reported to induce autophagy, which either protects cells or further sensitizes
      cells to drug treatment. However, the possible autophagic and antiproliferative
      effects of cardamonin on the human colorectal carcinoma HCT116 cell line are
      unclear. In the present study, experiments were conducted to determine the
      effects of cardamonin on cell proliferation, cell cycle distribution, and
      stimulation of autophagy in cultures of the HCT116 cell line. The results showed
      that cardamonin inhibited cell proliferation, induced G2/M phase cell cycle
      arrest, and enhanced autophagy in HCT116 cells. We found evidence that cardamonin
      induced autophagic and antiproliferative effects are regulated by the tumor
      protein p53. We also found that the enhanced activation of c-Jun N-terminal
      kinase (JNK) by cardamonin was partially regulated by p53 and was critical for
      cardamonin-induced autophagic and antiproliferative effects in HCT116 cells.
      These findings suggest that cardamonin or other anticancer agents that increase
      p53/JNK-dependent stimulation of autophagy could be used to effectively treat
      patients with colorectal carcinoma. 

PMID- 25959812
TI  - N-Arylmethylaminoquercitols, a new series of effective antidiabetic agents having
      alpha-glucosidase inhibition and antioxidant activity.
AB  - A new series of N-arylalkylaminoquercitols were synthesized by reductive
      amination of aminoquercitol bisacetonide 5 and a variety of aryl aldehydes. The
      targeted N-substituted aminoquercitols having phenolic moiety (7a-7c) displayed
      significantly enhanced alpha-glucosidase inhibition, which is 26-32 times more
      potent than that of the unmodified aminoquercitol 6. In addition, compounds 7a-7c
      also retained antioxidant activity with relatively more pronounced potency than
      their original phenolics. This recent finding suggests an approach to develop
      effective antidiabetic agents by incorporating antioxidative moiety into
      aminocyclitol core structure. 

PMID- 25959813
TI  - Design, synthesis and anticancer activity of matrine-1H-1,2,3-triazole-chalcone
      conjugates.
AB  - A series of novel matrine-1H-1,2,3-triazole-chalcone conjugates was synthesized
      and their anticancer activity against A549, Bel-7402, Hela, and MCF-7 cancer
      cells was evaluated. Most of the conjugates displayed higher potency than their
      components. Compounds 6h and 6i exhibited more potent anticancer activity than 5
      fluorouracil against the four tested human cancer cell lines and lower
      cytotoxicity to NIH3T3 normal cells. Flow cytometry tests demonstrated that
      compound 6h could induce apoptosis of A549 cells in a concentration-dependent
      manner. Moreover, 6h could efficiently suppress human tumor growth in mouse
      xenograft model without causing obvious toxicities. 

PMID- 25959814
TI  - Composite macroH2A/NRF-1 Nucleosomes Suppress Noise and Generate Robustness in
      Gene Expression.
AB  - The histone variant macroH2A (mH2A) has been implicated in transcriptional
      repression, but the molecular mechanisms that contribute to global mH2A-dependent
      genome regulation remain elusive. Using chromatin immunoprecipitation sequencing
      (ChIP-seq) coupled with transcriptional profiling in mH2A knockdown cells, we
      demonstrate that singular mH2A nucleosomes occupy transcription start sites of
      subsets of both expressed and repressed genes, with opposing regulatory
      consequences. Specifically, mH2A nucleosomes mask repressor binding sites in
      expressed genes but activator binding sites in repressed genes, thus generating
      distinct chromatin landscapes that limit genetic or extracellular inductive
      signals. We show that composite nucleosomes containing mH2A and NRF-1 are stably
      positioned on gene regulatory regions and can buffer transcriptional noise
      associated with antiviral responses. In contrast, mH2A nucleosomes without NRF-1
      bind promoters weakly and mark genes with noisier gene expression patterns. Thus,
      the strategic position and stabilization of mH2A nucleosomes in human promoters
      defines robust gene expression patterns. 

PMID- 25959815
TI  - RNAi Interrogation of Dietary Modulation of Development, Metabolism, Behavior,
      and Aging in C. elegans.
AB  - Diet affects nearly every aspect of animal life such as development, metabolism,
      behavior, and aging, both directly by supplying nutrients and indirectly through
      gut microbiota. C. elegans feeds on bacteria, and like other animals, different
      bacterial diets induce distinct dietary responses in the worm. However, the lack
      of certain critical tools hampers the use of worms as a model for dietary
      signaling. Here, we genetically engineered the bacterial strain OP50, the
      standard laboratory diet for C. elegans, making it compatible for dsRNA
      production and delivery. Using this RNAi-compatible OP50 strain and the other
      bacterial strain HT115, we feed worms different diets while delivering RNAi to
      interrogate the genetic basis underlying diet-dependent differential modulation
      of development, metabolism, behavior, and aging. We show by RNAi that
      neuroendocrine and mTOR pathways are involved in mediating differential dietary
      responses. This genetic tool greatly facilitates the use of C. elegans as a model
      for dietary signaling.

PMID- 25959816
TI  - Principles of long noncoding RNA evolution derived from direct comparison of
      transcriptomes in 17 species.
AB  - The inability to predict long noncoding RNAs from genomic sequence has impeded
      the use of comparative genomics for studying their biology. Here, we develop
      methods that use RNA sequencing (RNA-seq) data to annotate the transcriptomes of
      16 vertebrates and the echinoid sea urchin, uncovering thousands of previously
      unannotated genes, most of which produce long intervening noncoding RNAs
      (lincRNAs). Although in each species, >70% of lincRNAs cannot be traced to
      homologs in species that diverged >50 million years ago, thousands of human
      lincRNAs have homologs with similar expression patterns in other species. These
      homologs share short, 5'-biased patches of sequence conservation nested in exonic
      architectures that have been extensively rewired, in part by transposable element
      exonization. Thus, over a thousand human lincRNAs are likely to have conserved
      functions in mammals, and hundreds beyond mammals, but those functions require
      only short patches of specific sequences and can tolerate major changes in gene
      architecture. 

PMID- 25959817
TI  - An epigenetic memory of pregnancy in the mouse mammary gland.
AB  - Pregnancy is the major modulator of mammary gland activity. It induces a
      tremendous expansion of the mammary epithelium and the generation of alveolar
      structures for milk production. Anecdotal evidence from multiparous humans
      indicates that the mammary gland may react less strongly to the first pregnancy
      than it does to subsequent pregnancies. Here, we verify that the mouse mammary
      gland responds more robustly to a second pregnancy, indicating that the gland
      retains a long-term memory of pregnancy. A comparison of genome-wide profiles of
      DNA methylation in isolated mammary cell types reveals substantial and long
      lasting alterations. Since these alterations are maintained in the absence of the
      signal that induced them, we term them epigenetic. The majority of alterations in
      DNA methylation affect sites occupied by the Stat5a transcription factor and mark
      specific genes that are upregulated during pregnancy. We postulate that the
      epigenetic memory of a first pregnancy primes the activation of gene expression
      networks that promote mammary gland function in subsequent reproductive cycles.
      More broadly, our data indicate that physiological experience can broadly alter
      epigenetic states, functionally modifying the capacity of the affected cells to
      respond to later stimulatory events. 

PMID- 25959819
TI  - The Nav1.9 channel is a key determinant of cold pain sensation and cold
      allodynia.
AB  - Cold-triggered pain is essential to avoid prolonged exposure to harmfully low
      temperatures. However, the molecular basis of noxious cold sensing in mammals is
      still not completely understood. Here, we show that the voltage-gated Nav1.9
      sodium channel is important for the perception of pain in response to noxious
      cold. Nav1.9 activity is upregulated in a subpopulation of damage-sensing sensory
      neurons responding to cooling, which allows the channel to amplify subthreshold
      depolarizations generated by the activation of cold transducers. Consequently,
      cold-triggered firing is impaired in Nav1.9(-/-) neurons, and Nav1.9 null mice
      and knockdown rats show increased cold pain thresholds. Disrupting Nav1.9
      expression in rodents also alleviates cold pain hypersensitivity induced by the
      antineoplastic agent oxaliplatin. We conclude that Nav1.9 acts as a subthreshold
      amplifier in cold-sensitive nociceptive neurons and is required for the
      perception of cold pain under normal and pathological conditions. 

PMID- 25959818
TI  - Direct Activation of STING in the Tumor Microenvironment Leads to Potent and
      Systemic Tumor Regression and Immunity.
AB  - Spontaneous tumor-initiated T cell priming is dependent on IFN-beta production by
      tumor-resident dendritic cells. On the basis of recent observations indicating
      that IFN-beta expression was dependent upon activation of the host STING pathway,
      we hypothesized that direct engagement of STING through intratumoral (IT)
      administration of specific agonists would result in effective anti-tumor therapy.
      After proof-of-principle studies using the mouse STING agonist DMXAA showed a
      potent therapeutic effect, we generated synthetic cyclic dinucleotide (CDN)
      derivatives that activated all human STING alleles as well as murine STING. IT
      injection of STING agonists induced profound regression of established tumors in
      mice and generated substantial systemic immune responses capable of rejecting
      distant metastases and providing long-lived immunologic memory. Synthetic CDNs
      have high translational potential as a cancer therapeutic.

PMID- 25959820
TI  - SNAREs Controlling Vesicular Release of BDNF and Development of Callosal Axons.
AB  - At presynaptic active zones, exocytosis of neurotransmitter vesicles (SVs) is
      driven by SNARE complexes that recruit Syb2 and SNAP25. However, it remains
      unknown which SNAREs promote the secretion of neuronal proteins, including those
      essential for circuit development and experience-dependent plasticity. Here we
      demonstrate that Syb2 and SNAP25 mediate the vesicular release of BDNF in axons
      and dendrites of cortical neurons, suggesting these SNAREs act in multiple
      spatially segregated secretory pathways. Remarkably, axonal secretion of BDNF is
      also strongly regulated by SNAP47, which interacts with SNAP25 but appears to be
      dispensable for exocytosis of SVs. Cell-autonomous ablation of SNAP47 disrupts
      the layer-specific branching of callosal axons of projection cortical neurons in
      vivo, and this phenotype is recapitulated by ablation of BDNF or its receptor,
      TrkB. Our results provide insights into the molecular mechanisms of protein
      secretion, and they define the functions of SNAREs in BDNF signaling and
      regulation of neuronal connectivity.

PMID- 25959822
TI  - GABA-A Inhibition Shapes the Spatial and Temporal Response Properties of Purkinje
      Cells in the Macaque Cerebellum.
AB  - Data from in vitro and anesthetized preparations indicate that inhibition plays a
      major role in cerebellar cortex function. We investigated the role of GABA-A
      inhibition in the macaque cerebellar ventral-paraflocculus while animals
      performed oculomotor behaviors that are known to engage the circuit. We recorded
      Purkinje cell responses to these behaviors with and without application of
      gabazine, a GABA-A receptor antagonist, near the recorded neuron. Gabazine
      increased the neuronal responsiveness to saccades in all directions and the
      neuronal gain to VOR cancellation and pursuit, most significantly the eye and
      head velocity sensitivity. L-glutamate application indicated that these changes
      were not the consequence of increases in baseline firing rate. Importantly,
      gabazine did not affect behavior or efference copy, suggesting that only local
      computations were disrupted. Our data, collected while the cerebellum performs
      behaviorally relevant computations, indicate that inhibition is a potent
      regulatory mechanism for the control of input-output gain and spatial tuning in
      the cerebellar cortex.

PMID- 25959821
TI  - Differential connexin function enhances self-renewal in glioblastoma.
AB  - The coordination of complex tumor processes requires cells to rapidly modify
      their phenotype and is achieved by direct cell-cell communication through gap
      junction channels composed of connexins. Previous reports have suggested that gap
      junctions are tumor suppressive based on connexin 43 (Cx43), but this does not
      take into account differences in connexin-mediated ion selectivity and
      intercellular communication rate that drive gap junction diversity. We find that
      glioblastoma cancer stem cells (CSCs) possess functional gap junctions that can
      be targeted using clinically relevant compounds to reduce self-renewal and tumor
      growth. Our analysis reveals that CSCs express Cx46, while Cx43 is predominantly
      expressed in non-CSCs. During differentiation, Cx46 is reduced, while Cx43 is
      increased, and targeting Cx46 compromises CSC maintenance. The difference between
      Cx46 and Cx43 is reflected in elevated cell-cell communication and reduced
      resting membrane potential in CSCs. Our data demonstrate a pro-tumorigenic role
      for gap junctions that is dependent on connexin expression. 

PMID- 25959824
TI  - TGF-beta Signaling Regulates the Differentiation of Motile Cilia.
AB  - The cilium is a small cellular organelle with motility- and/or sensory-related
      functions that plays a crucial role during developmental and homeostatic
      processes. Although many molecules or signal transduction pathways that control
      cilia assembly have been reported, the mechanisms of ciliary length control have
      remained enigmatic. Here, we report that Smad2-dependent transforming growth
      factor beta (TGF-beta) signaling impacts the length of motile cilia at the
      Xenopus left-right (LR) organizer, the gastrocoel roof plate (GRP), as well as at
      the neural tube and the epidermis. Blocking TGF-beta signaling resulted in the
      absence of the transition zone protein B9D1/MSKR-1 from cilia in multi-ciliated
      cells (MCCs) of the epidermis. Interestingly, this TGF-beta activity is not
      mediated by Mcidas, Foxj1, and RFX2, the known major regulators of ciliogenesis.
      These data indicate that TGF-beta signaling is crucial for the function of the
      transition zone, which in turn may affect the regulation of cilia length.

PMID- 25959823
TI  - Apoptosis Triggers Specific, Rapid, and Global mRNA Decay with 3' Uridylated
      Intermediates Degraded by DIS3L2.
AB  - Apoptosis is a tightly coordinated cell death program that damages mitochondria,
      DNA, proteins, and membrane lipids. Little is known about the fate of RNA as
      cells die. Here, we show that mRNAs, but not noncoding RNAs, are rapidly and
      globally degraded during apoptosis. mRNA decay is triggered early in apoptosis,
      preceding membrane lipid scrambling, genomic DNA fragmentation, and apoptotic
      changes to translation initiation factors. mRNA decay depends on mitochondrial
      outer membrane permeabilization and is amplified by caspase activation. 3'
      truncated mRNA decay intermediates with nontemplated uridylate-rich tails are
      generated during apoptosis. These tails are added by the terminal uridylyl
      transferases (TUTases) ZCCHC6 and ZCCHC11, and the uridylated transcript
      intermediates are degraded by the 3' to 5' exonuclease DIS3L2. Knockdown of
      DIS3L2 or the TUTases inhibits apoptotic mRNA decay, translation arrest, and cell
      death, whereas DIS3L2 overexpression enhances cell death. Our results suggest
      that global mRNA decay is an overlooked hallmark of apoptosis. 

PMID- 25959825
TI  - The SLC7A7 Transporter Identifies Microglial Precursors prior to Entry into the
      Brain.
AB  - During development, macrophages invade organs to establish phenotypically and
      transcriptionally distinct tissue-resident populations. How they invade and
      colonize these organs is unclear. In particular, it remains to be established
      whether they arise from naive equivalents that colonize organs randomly or
      whether there are committed macrophages that follow pre-determined migration
      paths. Here, by using a combination of genetics and imaging approaches in the
      zebrafish embryo, we have addressed how macrophages colonize the brain to become
      microglia. Identification and cloning of a mutant that lacks microglia has shown
      that Slc7a7, a Leucine/Arginine transporter, defines a restricted macrophage sub
      lineage and is necessary for brain colonization. By taking a photoconversion
      approach, we show that these macrophages give rise to microglia. This study
      provides direct experimental evidence for the existence of sub-lineages among
      embryonic macrophages.

PMID- 25959827
TI  - Australian Rheumatology Associationin conjunction with Rheumatology Health
      Professionals Association, 56th Annual Scientific Meeting, Adelaide, South
      Australia, 23-26 May 2015.

PMID- 25959829
TI  - A "uniform" heterogeneous photocatalyst: integrated p-n type CuInS2/NaInS2
      nanosheets by partial ion exchange reaction for efficient H2 evolution.
AB  - Single-crystalline-like P-N type CuInS2/NaInS2 heterogeneous nanosheets were
      synthesized by partial cation exchange reaction and show highly improved
      photocatalytic H2 evolution activity attributed to the increased efficiency of
      interfacial charge transfer. 

PMID- 25959828
TI  - Minor genomic differences between related B6 and B10 mice affect severity of
      schistosome infection by governing the mode of dendritic cell activation.
AB  - Infection with the helminth Schistosoma mansoni results in hepatointestinal
      granulomatous inflammation mediated by CD4 T cells directed against parasite
      eggs. The severity of disease varies greatly in humans and mice; however, the
      genetic basis of such a heterogenous immune response remains poorly understood.
      Here we show that, despite their close genetic relationship, C57BL/10SnJ (B10)
      mice developed significantly more pronounced immunopathology and higher T helper
      17 cell responses than C57BL/6J (B6) mice. Similarly, live egg-stimulated B10
      derived dendritic cells (DCs) produced significantly more IL-1beta and IL-23,
      resulting in higher IL-17 production by CD4 T cells. Gene expression analysis
      disclosed a heightened proinflammatory cytokine profile together with a
      strikingly lower expression of Ym1 in B10 versus B6 mice, consistent with failure
      of B10 DCs to attain alternative activation. To genetically dissect the
      differential response, we developed and analyzed congenic mouse strains that
      capture major regions of allelic variation, and found that the level of
      inflammation was controlled by a relatively small number of genes in a locus
      mapping to chromosome 4 117-143 MB. Our study has thus identified novel genomic
      regions that regulate the severity of the schistosome infection by way of
      controlling the mode of DC activation and consequent CD4 T-cell subset
      development.

PMID- 25959826
TI  - Quantitative interaction proteomics of neurodegenerative disease proteins.
AB  - Several proteins have been linked to neurodegenerative disorders (NDDs), but
      their molecular function is not completely understood. Here, we used quantitative
      interaction proteomics to identify binding partners of Amyloid beta precursor
      protein (APP) and Presenilin-1 (PSEN1) for Alzheimer's disease (AD), Huntingtin
      (HTT) for Huntington's disease, Parkin (PARK2) for Parkinson's disease, and
      Ataxin-1 (ATXN1) for spinocerebellar ataxia type 1. Our network reveals common
      signatures of protein degradation and misfolding and recapitulates known biology.
      Toxicity modifier screens and comparison to genome-wide association studies show
      that interaction partners are significantly linked to disease phenotypes in vivo.
      Direct comparison of wild-type proteins and disease-associated variants
      identified binders involved in pathogenesis, highlighting the value of
      differential interactome mapping. Finally, we show that the mitochondrial protein
      LRPPRC interacts preferentially with an early-onset AD variant of APP. This
      interaction appears to induce mitochondrial dysfunction, which is an early
      phenotype of AD.

PMID- 25959830
TI  - Reliable transfer of multiple perforator-based pedicled flaps: Surgical technique
      and clinical outcomes.
AB  - PURPOSE: Although an increase in flap perfusion by incorporating multiple
      perforators has been demonstrated with free perforator flaps, whether the same
      efficacy can be achieved with pedicled flaps remains unclear, due to concerns
      regarding pedicle tension or kinking during flap transposition. The aim of this
      report was to investigate the reliability of multiple perforator-based pedicled
      flaps in a series of clinical cases. PATIENTS AND METHODS: Twenty-six patients
      undergoing soft tissue reconstruction using multiple perforator-based pedicled
      flaps from 2008 to 2012 were reviewed. The causes of the defects were oncologic
      (n = 15) or chronic wounds (n = 11). The defect sites were the trunk (n = 19),
      lower extremities (n = 4), head and neck (n = 2), and upper extremities (n = 1).
      Diverse flap types were used, including the superior gluteal artery perforator
      flap, the lateral femoral circumflex artery perforator flap, the medial femoral
      circumflex artery perforator flap, and the thoracodorsal artery perforator flap.
      The flaps were transposed in a rotation-and-advancement manner after
      skeletonizing each perforator and proximally dissecting the pedicle. The donor
      site was closed primarily. RESULTS: Mean flap size was 125.2 cm2 , and the mean
      number of perforators used was 2.3 (2-5). The mean angle of pivotal rotation for
      flap transposition was 132.8 degrees . No rotation-related problems including
      pedicle kinking or twisting developed, and all flaps survived completely. No
      significant donor-site morbidity was observed. The mean follow-up period was 38.1
      months. CONCLUSIONS: This report suggests that through meticulous dissection of
      pedicles of sufficient length, the multiple perforator-based pedicled flaps can
      be successfully transposed while minimizing the risk of pedicle tethering. (c)
      2015 Wiley Periodicals, Inc. Microsurgery 37:105-111, 2017.

PMID- 25959831
TI  - Aggression and anxiety in adolescent AAS-treated hamsters: A role for 5HT3
      receptors.
AB  - Previously, we have shown that anabolic androgenic steroid (AAS) exposure
      throughout adolescence stimulates offensive aggression while also reducing
      anxious behaviors during the exposure period. Interestingly, AAS exposure through
      development correlates with alterations to the serotonin system in regions known
      to contain 5HT3 receptors that influence the control of both aggression and
      anxiety. Despite these effects, little is known about whether these separate
      developmental AAS-induced behavioral alterations occur as a function of a common
      neuroanatomical locus. To begin to address this question, we localized 5HT3
      receptors in regions that have been implicated in aggression and anxiety. To
      examine the impact these receptors may have on AAS alterations to behavior, we
      microinjected the 5HT3 agonist mCPBG directly into a region know for its
      influence over aggressive behavior, the lateral division of the anterior
      hypothalamus, and recorded alterations to anxious behaviors using the elevated
      plus maze. AAS exposure primarily reduced the presence of 5HT3 receptors in
      aggression/anxiety regions. Accordingly, mCPBG blocked the anxiolytic effects of
      adolescent AAS exposure. These data suggest that the 5HT3 receptor plays a
      critical role in the circuit modulating developmental AAS-induced changes to both
      aggressive and anxious behaviors, and further implicates the lateral division of
      the anterior hypothalamus as an important center for the negative behavioral
      effects of developmental AAS-exposure. 

PMID- 25959832
TI  - Breast cancer outcomes in a population with high prevalence of obesity.
AB  - BACKGROUND: Obesity has been associated with poor prognosis in breast cancer.
      However, most previous studies examined populations with relatively low
      proportions of obese patients. Given that forecasts predict obesity rates to
      exceed 50% by 2030, it is important to examine breast cancer outcomes in
      populations with higher rates of obesity. We hypothesized that obesity, as
      measured by body mass index (BMI), is associated with decreased overall survival
      and disease-free survival in patients with invasive breast cancer in a population
      with a high prevalence of obesity. METHODS: A retrospective review of a
      prospectively maintained database was conducted on patients treated for invasive
      breast cancer at an academic medical center between 1997 and 2013. BMI was
      calculated from each patient's height and weight at the time of diagnosis.
      Patients were categorized as normal (BMI <25 kg/m(2)), overweight (BMI 25-30
      kg/m(2)), or obese (BMI >30 kg/m(2)), as per the definitions established by the
      World Health Organization. The end points of overall survival and disease-free
      survival were analyzed. RESULTS: A total of 523 patients with invasive breast
      cancer were included for analysis. Based on BMI, 87 (16%) were categorized as
      normal, 150 (29%) were overweight, and 286 (55%) were obese. The median follow-up
      was 49 mo. There were 16 deaths (18.4%) in normal patients, 25 (16.7 %) in
      overweight patients, and 45 (15.7%) in obese patients (P = 0.84). By Kaplan-Meier
      survival analysis, there were no differences in overall survival (P = 0.49) or in
      disease-free survival (P = 0.33) among the three groups. CONCLUSIONS: Obesity is
      not associated with decreased overall or disease-free survival in a patient
      population with a high prevalence of obesity. These findings suggest that there
      may be other factors that contribute to the poor prognosis of obese breast cancer
      patients observed in populations with lower rates of obesity.

PMID- 25959833
TI  - Surgical management and morbidity of pediatric magnet ingestions.
AB  - BACKGROUND: Foreign body ingestion remains a common reason for emergency room
      visits and operative interventions in the pediatric population. Rare earth magnet
      ingestion represents a low percentage of all foreign bodies swallowed by
      children; however, magnets swallowed in multiplicity can result in severe
      injuries. MATERIALS AND METHODS: Pediatric surgeons with membership in the
      Surgical Section of the American Academy of Pediatrics were surveyed to determine
      the magnitude and consequences of magnet ingestions in the pediatric population.
      RESULTS: About 100 (16%) participant responses reported on 99 magnet ingestions.
      The median age at ingestion was 3.7 y, and the majority of ingestions (71%)
      occurred after year 2010. Thirty-two children underwent endoscopy with successful
      removal in 70% of cases, and multiple magnets were found in 65% of these
      patients. Seventy-three children required either laparotomy (51) or laparoscopy
      (22) for magnet removal, and 90% of these children were discovered to have
      ingested more than one magnet. In addition, 17% of the children were found to
      have at least one perforation or fistula, and 34% of the children had multiple
      perforations or fistulae. Nine children required long-term care for their
      injuries including repeat endoscopies. One child died after hemorrhage from an
      esophago-aortic fistula. CONCLUSIONS: These results demonstrated the increasing
      need for magnet regulations and public awareness to prevent potentially serious
      complications.

PMID- 25959836
TI  - Simulation trainer for practicing emergent open thoracotomy procedures.
AB  - BACKGROUND: An emergent open thoracotomy (OT) is a high-risk, low-frequency
      procedure uniquely suited for simulation training. We developed a cost-effective
      Cardiothoracic (CT) Surgery trainer and assessed its potential for improving
      technical and interprofessional skills during an emergent simulated OT. MATERIALS
      AND METHODS: We modified a commercially available mannequin torso with artificial
      tissue models to create a custom CT Surgery trainer. The trainer's feasibility
      for simulating emergent OT was tested using a multidisciplinary CT team in three
      consecutive in situ simulations. Five discretely observable milestones were
      identified as requisite steps in carrying out an emergent OT; namely (1)
      diagnosis and declaration of a code situation, (2) arrival of the code cart, (3)
      arrival of the thoracotomy tray, (4) initiation of the thoracotomy incision, and
      (5) defibrillation of a simulated heart. The time required for a team to achieve
      each discrete step was measured by an independent observer over the course of
      each OT simulation trial and compared. RESULTS: Over the course of the three OT
      simulation trials conducted in the coronary care unit, there was an average
      reduction of 29.5% (P < 0.05) in the times required to achieve the five critical
      milestones. The time required to complete the whole OT procedure improved by 7
      min and 31 s from the initial to the final trial-an overall improvement of 40%.
      CONCLUSIONS: In our preliminary evaluation, the CT Surgery trainer appears to be
      useful for improving team performance during a simulated emergent bedside OT in
      the coronary care unit.

PMID- 25959834
TI  - Effect of limb demand ischemia on autophagy and morphology in mice.
AB  - BACKGROUND: Obesity is a major risk factor for diabetes and peripheral arterial
      disease, which frequently leads to lower limb demand ischemia. Skeletal muscle
      autophagy and mitochondrial biogenesis are important processes for proper
      oxidative capacity and energy metabolism, which are compromised in diabetes. This
      study compares autophagy, mitochondrial biogenesis, energy metabolism, and
      morphology in the hind limbs of obese diabetic mice subjected to demand or
      sedentary ischemia. MATERIALS AND METHODS: Unilateral hind limb demand ischemia
      was created in a group of diet-induced obese mice after femoral artery ligation
      and 4 wk of daily exercise. A parallel group of mice underwent femoral artery
      ligation but remained sedentary for 4 wk. Hind limb muscles were analyzed for
      markers of autophagy, mitochondrial biogenesis, adenosine triphosphate, and
      muscle tissue morphology. RESULTS: At the end of the 4-wk exercise period, demand
      ischemia increased the autophagy mediator Beclin-1, but it did not alter the
      autophagy indicator, LC3B-II/I ratio, or markers of mitochondrial biogenesis,
      optic atrophy/dynamin-related protein. In contrast, exercise significantly
      increased the level of mitochondrial protein-succinate dehydrogenase subunit-A
      and reduced adipocyte accumulation and the percentage of centrally nucleated
      myofibers in the demand ischemia limb. In addition, demand ischemia resulted in
      decreased uncoupling protein-3 levels without altering muscle adenosine
      triphosphate or pS473-Akt levels. CONCLUSIONS: Limb demand ischemia markedly
      decreased adipocyte accumulation and enhanced muscle regeneration in obese mice,
      but it did not appear to enhance autophagy, mitochondrial biogenesis, energy
      metabolism, or insulin sensitivity. Future studies aimed at evaluating novel
      therapies that enhance autophagy and mitochondrial biogenesis in diabetes with
      peripheral arterial disease are warranted.

PMID- 25959835
TI  - Secondary overtriage in a statewide rural trauma system.
AB  - BACKGROUND: Rural hospitals have variable degrees of involvement within the
      nationwide trauma system because of differences in resources and operational
      goals. "Secondary overtriage" refers to the patient who is discharged home
      shortly after being transferred from another hospital. An analysis of these
      occurrences is useful to determine the efficiency of the trauma system as a
      whole. MATERIALS AND METHODS: Data were extracted from a statewide trauma
      registry from 2007-2012 to include those who were (1) discharged home within 48 h
      of arrival and (2) did not undergo a surgical procedure. We then identified those
      who arrived as a transfer before being discharged (secondary overtriage) from
      those who arrived from the scene. Factors associated with transfers were analyzed
      using a logistic regression. Injuries were classified based on the need of a
      specific consultant. Time of arrival to the emergency department was analyzed
      using 8-h blocks, with the 7 AM-3 PM block as reference. RESULTS: A total of
      19,319 patients fit our inclusion criteria of which 1897 (9.8%) arrived as
      transfers. Descriptive analysis showed a number of differences between transfers
      and nontransfers because of our large sample size. Thus, we examined variables
      that had more clinical significance using logistic regression controlling for
      age, injury severity score, the type of injury, blood products given, the time of
      arrival to initial emergency room, and whether a computed tomography scan was
      obtained initially. Factors associated with being transferred were injury
      severity score >15, transfusion of packed-red-blood-cells, graveyard-shift
      arrivals, and neurosurgical, spine, and facial injuries. Patients having a
      computed tomography scan were less likely to be transferred. CONCLUSIONS:
      Secondary overtriage may result from the hospital's limited resources. Some of
      these limitations are the availability of surgical specialists, blood products,
      and overall coverage during the "graveyard-shift." However, some of these
      transfers may be appropriate even though patients are ultimately discharged
      shortly after transfer.

PMID- 25959837
TI  - 5, 4, 3, 2, 1: embryologic variants of pentalogy of Cantrell.
AB  - BACKGROUND: The purpose of this study was to evaluate our experience with
      pentalogy of Cantrell and the various embryologic variants. MATERIALS AND
      METHODS: Patient charts and diagnostic imaging studies of all fetuses evaluated
      at Texas Children's Fetal Center for pentalogy of Cantrell between April 2004 and
      June 2014 were reviewed retrospectively. Data collected from patient charts
      included demographic information, clinical presentation, fetal and postnatal
      imaging findings, operative treatment, pathologic evaluation, and outcomes.
      RESULTS: There were 10 patients who presented with embryologic variants of
      pentalogy of Cantrell over a 6-y period. Two cases displayed the full range of
      embryologic defects observed, and eight cases exhibited variants of the classic
      pentalogy. Sternal and pericardial defects were each present in 40% of patients.
      Additional anomalies present included pulmonary hypoplasia, pulmonary artery
      stenosis, and chromosomal abnormalities. Four patients presented with
      diaphragmatic defects but no defect in the pericardium, and one patient presented
      with a defective pericardium but no associated diaphragmatic defect, suggesting
      highly specific losses of somatic mesoderm during embryologic development. One
      patient was lost to follow-up, and a second patient underwent termination of
      pregnancy. Five of the remaining eight patients survived, one of which had the
      full range of embryologic defects and now attends preschool but requires speech
      and occupational therapy. The remaining surviving patients have developed without
      serious sequelae. CONCLUSIONS: This report highlights the spectrum of anomalies
      observed in the pentalogy of Cantrell and demonstrates that these fetuses can
      survive but with substantial morbidity.

PMID- 25959839
TI  - A multi-reference study of the byproduct formation for a ring-closed
      dithienylethene photoswitch.
AB  - Photodriven molecular switches are sometimes hindered in their performance by
      forming byproducts which act as dead ends in sequences of switching cycles,
      leading to rapid fatigue effects. Understanding the reaction pathways to unwanted
      byproducts is a prerequisite for preventing them. This article presents a study
      of the photochemical reaction pathways for byproduct formation in the
      photochromic switch 1,2-bis-(3-thienyl)-ethene. Specifically, using single- and
      multi-reference methods the post-deexcitation reaction towards the byproduct in
      the electronic ground state S0 when starting from the S1-S0 conical intersection
      (CoIn), is considered in detail. We find an unusual low-energy pathway, which
      offers the possibility for the formation of a dyotropic byproduct. Several high
      energy pathways can be excluded with high probability. 

PMID- 25959838
TI  - Hospital readmission after emergency room visit for cholelithiasis.
AB  - BACKGROUND: For patients presenting with symptomatic cholelithiasis,
      cholecystectomy is the definitive treatment modality. Our goal was to evaluate
      the surgical follow-up and outcomes in patients seen in the emergency department
      (ED) for an episode of symptomatic cholelithiasis and discharged home for
      elective follow-up. METHODS: We performed a retrospective review of consecutive
      patients seen in the ED for cholelithiasis and discharged without hospital
      admission between August 2009 and May 2014. All patients were followed for 2 y
      from the date of the initial ED visit. We evaluated outpatient surgeon visits,
      elective and emergent cholecystectomy rates, and additional ED visits. Cumulative
      incidence and Kaplan-Meier curves were used to examine the time from the initial
      ED visit to outpatient surgeon evaluation and the time from the initial ED visit
      to ED readmission. RESULTS: Seventy-one patients were discharged from the ED with
      a diagnosis of symptomatic gallstones. Patients who had an elective
      cholecystectomy in the 2 y after the initial visit were 12.6%. In this group, the
      mean time from the initial ED visit to outpatient surgeon follow-up was 7.7 d,
      and all elective cholecystectomies occurred within 1 mo of the initial visit. Of
      the 62 patients who did not have an elective cholecystectomy, only 14.5% of
      patients in this group had outpatient surgeon follow-up at mean time of 137 d
      from the initial ED visit for symptomatic gallstones. In addition, 37.1% of
      patients in this group had additional ED visits for gallstone-related symptoms,
      with 17.7% of patients having two or more additional ED visits, and 12.9%
      required emergent and/or urgent cholecystectomy. Additional ED visits (43.5%)
      occurred within 1 mo and 60.9% within 3 mo of their initial ED visit. In patients
      with additional ED visits for symptomatic cholelithiasis, 60.9% had more than one
      abdominal ultrasound or computed tomography scan during the course of multiple
      visits. CONCLUSIONS: Failure to achieve a timely surgical follow-up leads to
      multiple ED readmissions and emergent gallstone-related hospitalizations,
      including emergency cholecystectomy. System-level interventions to ensure
      outpatient surgical follow-up within 1-2 wk of the initial ED visit has the
      potential to improve outcomes for patients with symptomatic biliary colic.

PMID- 25959840
TI  - A highly robust metal-organic framework based on an aromatic 12-carboxyl ligand
      with highly selective adsorption of CO2 over CH4.
AB  - A highly robust MOF based on a 12-carboxyl dendritic aromatic ligand and two Cd
      clusters is successfully synthesized. This activated MOF exhibits high heat of
      absorption of CO2 and highly selective adsorption of CO2 over CH4. Especially, a
      new type of topology (hhm-a) is presented.

PMID- 25959841
TI  - Acrylamide inhibits cellular differentiation of human neuroblastoma and
      glioblastoma cells.
AB  - This study explores human neuroblastoma (SH-SY5Y) and human glioblastoma (U-1240
      MG) cellular differentiation changes under exposure to acrylamide (ACR).
      Differentiation of SH-SY5Y and U-1240 MG cells were induced by retinoic acid (RA)
      and butyric acid (BA), respectively. Morphological observations and MTT assay
      showed that the induced cellular differentiation and cell proliferation were
      inhibited by ACR in a time- and dose-dependent manner. ACR co-treatment with RA
      attenuated SH-SY5Y expressions of neurofilament protein-L (NF-L), microtubule
      associated protein 1b (MAP1b; 1.2 to 0.7, p < 0.001), MAP2c (2.2 to 0.8, p <
      0.05), and Janus kinase1 (JAK1; 1.9 to 0.6, p < 0.001), while ACR co-treatment
      with BA attenuated U-1240 MG expressions of glial fibrillary acidic protein
      (GFAP), MAP1b (1.2 to 0.6, p < 0.001), MAP2c (1.5 to 0.7, p < 0.01), and JAK1
      (2.1 to 0.5, p < 0.001), respectively. ACR also decreased the phosphorylation of
      extracellular-signal-regulated kinases (ERK) and c-Jun N-terminal kinases (JNK)
      in U-1240 MG cells, while caffeine reversed this suppression of ERK and JNK
      phosphorylation caused by ACR treatment. These results showed that RA-induced
      neurogenesis of SH-SY5Y and BA-induced astrogliogenesis of U-1240 MG cells were
      attenuated by ACR and were associated with down-regulation of MAPs expression and
      JAK-STAT signaling. 

PMID- 25959842
TI  - Peripartum cardiomyopathy in the ED.

PMID- 25959843
TI  - Bioelectrical impedance analysis for heart failure diagnosis in the ED.
AB  - INTRODUCTION: The aim of this study was to evaluate bioimpedance vector analysis
      (BIVA) for the diagnosis of acute heart failure (AHF) in patients presenting with
      acute dyspnea to the emergency department (ED). METHODS: Patients with acute
      dyspnea presenting to the ED were prospectively enrolled. Four parameters were
      assessed: resistance (R), reactance (Ra), total body water (TBW), and
      extracellular body water (EBW). Brain natriuretic peptide (BNP) measures and
      cardiac ultrasound studies were performed in all patients at admission. Patients
      were classified into AHF and non-AHF groups retrospectively by expert
      cardiologists. RESULTS: Seventy-seven patients (39 men; age, 68+/-14years;
      weight, 79.8+/-20.6 kg) were included. Of the 4 BIVA parameters, Ra was
      significantly lower in the AHF compared to non-AHF group (32.7+/-14.3 vs 45.4+/
      19.7; P<.001). Brain natriuretic peptide levels were significantly higher in the
      AHF group (1050.3+/-989 vs 148.7+/-181.1ng/L; P<.001). Reactance levels were
      significantly correlated to BNP levels (r=-0.5; P<.001). Patients with different
      mitral valve Doppler profiles (E/e'<=8, E/e' >=9 and <15, and E/e'>=15) had
      significant differences in Ra values (47.9+/-19.9, 34.7+/-19.4, and 31.2+/-11.7,
      respectively; P=.003). Overall, the sensitivity of BIVA for AHF diagnosis with a
      Ra cutoff at 39Omega was 67% with a specificity of 76% and an area under the
      curve at 0.76. However, Ra did not significantly improve the area under the curve
      of BNP for the diagnosis of AHF (P=not significant). CONCLUSION: In a population
      of patients presenting to the ED with dyspnea, BIVA was significantly related to
      the AHF status but did not improve the diagnostic performance for AHF in addition
      to BNP alone.

PMID- 25959845
TI  - The outcomes of elderly ED patients intubated because of community acquired
      pneumonia: why not give noninvasive ventilation a chance?

PMID- 25959844
TI  - A comparison of ED and direct admission care of cancer patients with febrile
      neutropenia.
AB  - OBJECTIVE: We compared the quality of care in admitted febrile neutropenic cancer
      patients presenting through the emergency department (ED) vs those directly
      admitted (DA) from the clinic or infusion center. We hypothesized that the
      quality of care would be comparable between these 2 pathways. METHODS: We
      conducted a retrospective, observational cohort study of all adult cancer
      patients hospitalized with subjective or objective fever (>=100.4 degrees F) and
      documented neutropenia (absolute neutrophil count <=1000/mm(3)) from January 1,
      2011 to June 30, 2013, at 2 hospitals. Two investigators retrieved data including
      patient age, sex, race, tumor type, blood culture growth, temperature (actual or
      reported), pathway to admission (ED or DA), time to antibiotic administration,
      length of stay, and the Multinational Association for Supportive Care in Cancer
      (MASCC) risk score. The primary outcome measures were time to antibiotic
      administration, appropriateness of antibiotic(s) administered based on published
      guidelines, length of stay, and MASCC score-based risk assessment. We used the t
      test for the difference between 2 means with unequal population variances to
      compare these outcome measures between ED and DA patients. RESULTS: One hundred
      twenty-seven visits met inclusion criteria (42 [33%] ED visits, 85 [67%] DA
      visits). Mean time to antibiotic administration, mean length of stay,
      appropriateness of antibiotics, and MASCC score-based risk assessment were
      comparable between ED and DA visits (P>.05 for all comparisons). CONCLUSION: The
      quality of care for febrile neutropenia in patients presenting through the ED was
      comparable to those directly admitted to the hospital in this 2-center study.

PMID- 25959846
TI  - The authors respond.

PMID- 25959847
TI  - Different clinical presentation of community-onset bacteremia among neutropenic
      adults in the ED.
AB  - OBJECTIVES: To analyze the differences in clinical presentation and
      characteristics of community-onset bacteremia between neutropenic and
      nonneutropenic adults visiting the emergency department. METHODS: A case-control
      study with a ratio of 1:2 was conducted retrospectively over a 6-year period.
      Demographic characteristics, microorganisms, severity of illness, and clinical
      outcomes determined from medical records were analyzed. RESULTS: In total, 116
      neutropenic adults (case patients) and 232 nonneutropenic adults (control
      patients) were examined. Significant differences in the source of bacteremia,
      susceptibility, and species of bacteremia-causing organisms between the case
      patients and control patients were observed by univariate analyses. Significantly
      more patients presenting with an initial syndrome of severe sepsis or septic
      shock at the emergency department, having high Pittsburgh bacteremia scores (>=4
      points) or having severe comorbidities (McCabe classification), and high 28-day
      mortality rates were discovered in the case group, compared with the control
      group. Of note, Pseudomonas aeruginosa (32/137 [23.4%] vs 8/272 [2.9%], P < .001)
      was more often isolated from the case patients. In a further analysis using a
      multivariate regression to demonstrate the independent predictors of P aeruginosa
      infection, patients with neutropenia remained as an independent risk factors
      (odds ratio, 7.48; P < .001). CONCLUSIONS: This study demonstrated obvious
      differences of community-onset bacteremia in severity, the distribution of
      microorganisms, and susceptibility between neutropenic and nonneutropenic
      patients. Antipseudomonas therapy was empirically suggested for neutropenic
      patients with community-onset bacteremia and reducing the need for a
      glycopeptide.

PMID- 25959848
TI  - Improved sepsis bundles in the treatment of septic shock: a prospective clinical
      study.
AB  - BACKGROUND: Sepsis bundles can decrease mortality in patients with severe sepsis
      or septic shock. However, current methods of measuring pressure, such as central
      venous pressure, are inadequate. This study investigated the effect of improved
      sepsis bundles informed by pulse-indicated continuous cardiac output. METHODS: We
      compared the outcome of treatment with sepsis bundles informed by either
      conventional pressure measurements or pulse-indicated continuous cardiac output.
      Patients in 2 groups received fluid resuscitation, standard antibiotics, and
      oxygen therapy. RESULTS: A total of 105 patients with septic shock were randomly
      divided into 2 groups: the conventional sepsis bundle group (n = 52) or the
      improved sepsis bundle group (ISBG, n =53). The ISBG significantly reduced the
      mean Acute Physiology and Chronic Health Evaluation II and Sepsis-related Organ
      Failure Assessment scores. Significantly fewer ISBG-treated patients received
      vasoactive drugs compared to conventional sepsis bundle group-treated patients.
      In addition, patients in the ISBG exhibited a significantly increased arterial
      blood lactate clearance rate and required less total fluid resuscitation and a
      shorter duration of mechanical ventilation and stay in the intensive care unit.
      CONCLUSIONS: Pulse-indicated continuous cardiac output-directed sepsis bundles
      can reduce the severity of septic shock, provide more accurate fluid
      resuscitation, and reduce the duration of mechanical ventilation and stay in the
      intensive care unit.

PMID- 25959849
TI  - Nickel-catalyzed cross-coupling reactions of o-carboranyl with aryl iodides:
      facile synthesis of 1-aryl-o-carboranes and 1,2-diaryl-o-carboranes.
AB  - A nickel-catalyzed arylation at the carbon center of o-carborane cages has been
      developed, thus leading to the preparation of a series of 1-aryl-o-carboranes and
      1,2-diaryl-o-carboranes in high yields upon isolation. This method represents the
      first example of transition metal catalyzed C,C'-diarylation by cross-coupling
      reactions of o-carboranyl with aryl iodides. 

PMID- 25959851
TI  - Sensing and surviving hypoxia in vertebrates.
AB  - Surviving hypoxia is one of the most critical challenges faced by vertebrates.
      Most species have adapted to changing levels of oxygen in their environment with
      specialized organs that sense hypoxia, while only few have been uniquely adapted
      to survive prolonged periods of anoxia. The goal of this review is to present the
      most recent research on oxygen sensing, adaptation to hypoxia, and mechanisms of
      anoxia tolerance in nonmammalian vertebrates. We discuss the respiratory
      structures in fish, including the skin, gills, and air-breathing organs, and
      recent evidence for chemosensory neuroepithelial cells (NECs) in these tissues
      that initiate reflex responses to hypoxia. The use of the zebrafish as a genetic
      and developmental model has allowed observation of the ontogenesis of respiratory
      and chemosensory systems, demonstration of a putative intracellular O2 sensor in
      chemoreceptors that may initiate transduction of the hypoxia signal, and
      investigation into the effects of extreme hypoxia on cardiorespiratory
      development. Other organisms, such as goldfish and freshwater turtles, display a
      high degree of anoxia tolerance, and these models are revealing important
      adaptations at the cellular level, such as the regulation of glutamatergic and
      GABAergic neurotransmission in defense of homeostasis in central neurons. 

PMID- 25959850
TI  - Exposure-effect relationship of mycophenolic acid and prednisolone in adult
      patients with lupus nephritis.
AB  - AIMS: The aim was to examine relationships between total and unbound mycophenolic
      acid (MPA) and prednisolone exposure and clinical outcomes in patients with lupus
      nephritis. METHODS: Six blood samples were drawn pre- and at 1, 2, 4, 6 and 8 h
      post-dose and total and unbound MPA and prednisolone pre-dose (C0 ), maximum
      concentration (Cmax ) and area under the concentration-time curve (AUC) were
      determined using non-compartmental analysis in 25 patients. The analyses
      evaluated drug exposures in relation to treatment response since starting MPA and
      drug-related adverse events. RESULTS: Dose-normalized AUC varied 10-, 8-, 7- and
      19-fold for total MPA, unbound MPA, total prednisolone and unbound prednisolone,
      respectively. Median values (95% CI) of total MPA AUC(0,8 h) (21.5 [15.0, 42.0]
      vs. 11.2 [4.8, 30.0] mg l(-1) h, P= 0.048) and Cmax (11.9 [6.7, 26.3] vs. 6.1
      [1.6, 9.2] mg l(-1) , P = 0.016) were significantly higher in responders than non
      responders. Anaemia was significantly associated with higher total (37.8 [14.1,
      77.5] vs. 18.5 [11.7, 32.7] mg l(-1) h, P = 0.038) and unbound MPA AUC(0,12 h)
      (751 [214, 830] vs. 227 [151, 389] mg l(-1) h, P = 0.004). Unbound prednisolone
      AUC(0,24 h) was significantly higher in patients with Cushingoid appearance
      (unbound: 1372 [1242, 1774] vs. 846 [528, 1049] nmol l(-1) h, P = 0.019) than in
      those without. Poorer treatment response was observed in patients with lowest
      tertile exposure to both total MPA and prednisolone as compared with patients
      with middle and higher tertile exposure (17% vs. 74%, P = 0.023). CONCLUSIONS:
      This study suggests a potential role for therapeutic drug monitoring in
      individualizing immunosuppressant therapy in patients with lupus nephritis.

PMID- 25959852
TI  - Speciation control during Suzuki-Miyaura cross-coupling of haloaryl and
      haloalkenyl MIDA boronic esters.
AB  - Boronic acid solution speciation can be controlled during the Suzuki-Miyaura
      cross-coupling of haloaryl N-methyliminodiacetic acid (MIDA) boronic esters to
      enable the formal homologation of boronic acid derivatives. The reaction is
      contingent upon control of the basic biphase and is thermodynamically driven:
      temperature control provides highly chemoselective access to either BMIDA adducts
      at room temperature or boronic acid pinacol ester (BPin) products at elevated
      temperature. Control experiments and solubility analyses have provided some
      insight into the mechanistic operation of the formal homologation process. 

PMID- 25959853
TI  - How to increase the benefits of cooperation: Effects of training in transactive
      communication on cooperative learning.
AB  - BACKGROUND: Transactive communication means referring to and building on a
      learning partner's idea, by, for example, extending the partner's idea or
      interlinking the partner's idea with an idea of one's own. This transforms the
      partner's idea into a more elaborate one. Previous research found a positive
      relationship between students' transactive communication and their learning
      results when working in small groups. AIMS: To increase the benefits of
      cooperation, we developed and tested a module for training students in
      transactive communication. We assumed that this training would enhance students'
      transactive communication and also increase their knowledge acquisition during
      cooperative learning. Further, we distinguished between an actor's transactive
      communication and a learning partner's transactive communication and expected
      both to be positively associated with an actor's knowledge acquisition. SAMPLE:
      Participants were 80 university students. METHODS: In an experiment with pre- and
      post-test measurements, transactive communication was measured by coding
      students' communication in a cooperative learning situation before training and
      in another cooperative learning situation after training. For the post-test
      cooperative learning situation, knowledge was pre-tested and post-tested.
      RESULTS: Trained students outperformed controls in transactive communication and
      in knowledge acquisition. Positive training effects on actors' knowledge
      acquisition were partially mediated by the improved actors' transactive
      communication. Moreover, actors' knowledge acquisition was positively influenced
      by learning partners' transactive communication. CONCLUSIONS: Results show a
      meaningful increase in the benefits of cooperation through the training in
      transactive communication. Furthermore, findings indicate that students benefit
      from both elaborating on their partner's ideas and having their own ideas
      elaborated on.

PMID- 25959855
TI  - Family caregivers - a precious resource.

PMID- 25959856
TI  - DNA hydrogel delivery vehicle for light-triggered and synergistic cancer therapy.
AB  - A DNA hydrogel is reported as a delivery vehicle for gold nanorods and
      doxorubicin. The two photothermal and chemo cancer agents were co-loaded using
      electrostatic and DNA binding interactions, respectively. Light-triggered and
      highly synergistic combination cancer therapy was demonstrated in cellular and
      animal models. 

PMID- 25959857
TI  - Current use of active surveillance for localized prostate cancer: A nationwide
      survey in Japan.
AB  - OBJECTIVE: To understand the current practice pattern of active surveillance
      using a nationwide survey among Japanese urologists. METHODS: A new questionnaire
      about active surveillance was developed and mailed to 863 training institutes in
      January 2014. The questionnaire included indications for active surveillance,
      percentage of active surveillance for localized prostate cancer, problems with
      active surveillance, which protocol was used, timing of first repeat biopsy, use
      of prostate-specific antigen or doubling time and use of magnetic resonance
      imaging. RESULTS: A total of 2133 Japanese urologists in the 632 training
      institutes answered the questionnaire. The median age was 42 years (26-84 years).
      Of the responders, 26.9% had no use of active surveillance for localized prostate
      cancer. The Prostate Cancer Research International: Active Surveillance criteria
      were most frequently used (29.7%), followed by a low-risk group without a
      definitive follow-up protocol (29.4%). Regarding repeat biopsy, 40.6% carried it
      out at 1 year after active surveillance initiation, but 24.1% did not usually
      carry it out and 31.8% carried it out only when they considered it necessary.
      Magnetic resonance imaging was used routinely in 22.2% and as required in 67.6%.
      Re-biopsy or magnetic resonance imaging was less carried out in general hospitals
      than in universities. The percentage of no usual repeat biopsy was significantly
      higher in urologists who had more than 10 years of experience. Repeat biopsies
      (60.3%), inadequate inclusion criteria (49.9%), psychological burden for patients
      (43.7%), unexpected progression (41.1%) and unknown long-term outcomes (40.6%)
      were considered the major problems of active surveillance in the responders.
      CONCLUSIONS: The practice pattern of active surveillance varies widely among
      Japanese urologists. It is necessary to gain a correct understanding of active
      surveillance.

PMID- 25959854
TI  - Major differences in organization and availability of health care and medicines
      for HIV/TB coinfected patients across Europe.
AB  - OBJECTIVES: The aim of the study was to investigate the organization and delivery
      of HIV and tuberculosis (TB) health care and to analyse potential differences
      between treatment centres in Eastern (EE) and Western Europe (WE). METHODS:
      Thirty-eight European HIV and TB treatment centres participating in the TB:HIV
      study within EuroCoord completed a survey on health care management for
      coinfected patients in 2013 (EE: 17 respondents; WE:21; 76% of all TB:HIV
      centres). Descriptive statistics were obtained for regional comparisons. The
      reported data on health care strategies were compared with actual clinical
      practice at patient level via data derived from the TB:HIV study. RESULTS:
      Respondent centres in EE comprised: Belarus (n = 3), Estonia (1), Georgia (1),
      Latvia (1), Lithuania (1), Poland (4), Romania (1), the Russian Federation (4)
      and Ukraine (1); those in WE comprised: Belgium (1), Denmark (1), France (1),
      Italy (7), Spain (2), Switzerland (1) and UK (8). Compared with WE, treatment of
      HIV and TB in EE are less often located at the same site (47% in EE versus 100%
      in WE; P < 0.001) and less often provided by the same doctors (41% versus 90%,
      respectively; P = 0.002), whereas regular screening of HIV-infected patients for
      TB (80% versus 40%, respectively; P = 0.037) and directly observed treatment (88%
      versus 20%, respectively; P < 0.001) were more common in EE. The reported
      availability of rifabutin and second- and third-line anti-TB drugs was lower, and
      opioid substitution therapy (OST) was available at fewer centres in EE compared
      with WE (53% versus 100%, respectively; P < 0.001). CONCLUSIONS: Major
      differences exist between EE and WE in relation to the organization and delivery
      of health care for HIV/TB-coinfected patients and the availability of anti-TB
      drugs and OST. Significant discrepancies between reported and actual clinical
      practices were found in EE.

PMID- 25959858
TI  - Food insecurity during pregnancy leads to stress, disordered eating, and greater
      postpartum weight among overweight women.
AB  - OBJECTIVE: To investigate the influence of food insecurity on women's stress,
      disordered eating, dietary fat intake, and weight during the postpartum period.
      METHODS: The association between marginal food security and food insecurity
      measured during pregnancy and postpartum-and stress, disordered eating, dietary
      fat intake, and weight at 3 and 12 months postpartum was estimated using
      multivariate linear regression, controlling for demographic and socioeconomic
      characteristics and health behaviors. Effect modification between level of food
      insecurity and prepregnancy weight status was assessed, hypothesizing a stronger
      association would be found among women who started pregnancy with overweight or
      obesity. RESULTS: Food insecurity status during pregnancy was strongly associated
      with higher levels of stress, disordered eating, and dietary fat intake at 3 and
      12 months postpartum; during the postpartum period, food insecurity was
      associated with these measures at 12 months postpartum. A significant interaction
      was found between level of food insecurity and prepregnancy weight status; food
      insecurity was associated with greater weight and BMI at 12 months only among
      women with overweight or obesity. CONCLUSIONS: In order to return to one's
      prepregnancy weight, women with overweight and obesity who face household food
      insecurity may need multipronged assistance that not only addresses having enough
      high-quality food, but also include stress reduction and eating behavior
      interventions.

PMID- 25959859
TI  - Population-based study of long-term functional outcomes after prostate cancer
      treatment.
AB  - OBJECTIVE: To evaluate long-term urinary, sexual and bowel functional outcomes
      after prostate cancer treatment at a median (interquartile range) follow-up of 12
      (11-13) years. PATIENTS AND METHODS: In this nationwide, population-based study,
      we identified 6 003 men diagnosed with localized prostate cancer (clinical local
      stage T1-2, any Gleason score, prostate-specific antigen <20 ng/mL, NX or N0, MX
      or M0) between 1997 and 2002 from the National Prostate Cancer Register, Sweden.
      The men were aged <=70 years at diagnosis. A control group of 1 000 men without
      prostate cancer were also selected, matched for age and county of residence.
      Functional outcomes were evaluated with a validated self-reported questionnaire.
      RESULTS: Responses were obtained from 3 937/6 003 cases (66%) and 459/1 000 (46%)
      controls. At 12 years after diagnosis and at a median age of 75 years, the
      proportion of cases with adverse symptoms was 87% for erectile dysfunction/sexual
      inactivity, 20% for urinary incontinence and 14% for bowel disturbances. The
      corresponding proportions for controls were 62, 6 and 7%, respectively. Men with
      prostate cancer, except those on surveillance, had an increased risk of erectile
      dysfunction compared with the men in the control group. Radical prostatectomy was
      associated with an increased risk of urinary incontinence (odds ratio [OR] 1.89,
      95% confidence interval [CI] 1.36-2.62) and radiotherapy increased the risk of
      bowel dysfunction (OR 2.46, 95% CI 1.73-3.49) compared with men in the control
      group. Multi-modal treatment, in particular treatment including androgen
      deprivation therapy (ADT), was associated with the highest risk of adverse
      effects; for instance, radical prostatectomy followed by radiotherapy and ADT was
      associated with an OR of 3.74 (95% CI 1.76-7.95) for erectile dysfunction and an
      OR of 3.22 (95% CI 1.93-5.37) for urinary incontinence. CONCLUSION: The
      proportion of men who experienced a long-term impact on functional outcomes after
      prostate cancer treatment was substantial.

PMID- 25959860
TI  - Metformin, but not sitagliptin, enhances WP 631-induced apoptotic HepG2 cell
      death.
AB  - Metformin and sitagliptin are hypoglycemic drugs with potential use in cancer
      treatment. Evidence indicates that metformin may inhibit the proliferation and
      growth of various types of cancer cells. Data regarding the relationship between
      sitagliptin and cancer cells is limited. Therapy based on anthracycline
      derivatives, mainly doxorubicin, is commonly used in the treatment of resistant
      liver cancers. WP 631 is a new structural analogue of doxorubicin that exerts an
      anticancer action by the induction of apoptosis. The aim of this study was to
      compare the effect of metformin and sitagliptin on WP 631-induced apoptotic cell
      death in a human hepatocarcinoma cell line (HepG2). HepG2 cancer cells are known
      to be resistant to chemotherapeutic cytotoxic agents. Both MTT assay and flow
      cytometry analysis showed that WP 631 reduced the growth of HepG2 cells by
      apoptosis induction, accompanied by elevated NF-kappaB and p53 levels. Metformin
      enhanced the pro-apoptotic effect of WP 631, increasing the NF-kappaB level but
      not the p53 level. Sitagliptin did not affect the action of WP 631 in HepG2
      cancer cells, however, it increased the p53 level. To conclude, our results
      suggest that metformin significantly enhances the efficacy of anthracycline
      derivative, although this effect is not observed in the case of sitagliptin.
      Therefore, metformin seems to be a good candidate for combined therapy of
      resistant liver cancer with anthracycline derivatives. 

PMID- 25959861
TI  - Gender differences in psychological well-being: tests of factorial invariance.
AB  - PURPOSE: This research investigated gender differences in the six factors of Li's
      18-item version of Ryff's psychological well-being (PWB) scale by using factorial
      invariance procedures. This version improved on Ryff's shorter PWB scale in
      regard to the reliability of each subscale. METHODS: The sample comprised 653
      adult participants, specifically, 271 men and 382 women. Factorial invariance
      tests were conducted using multigroup confirmatory factor analysis. RESULTS: The
      results showed that the Li's version of Ryff's PWB scale has configural
      invariance, factor loading invariance, intercept invariance, partial invariance
      of factor variances and covariances, partial invariance of latent means, and
      partial invariance of error variances. According to latent means, women had
      significantly less autonomy (AU) and more environmental mastery (EM) than men
      did. Moreover, based on interfactor correlations, the correlation of EM and self
      acceptance was higher for men than for women, and the correlation of positive
      relations with others and AU was lower for men than for women. CONCLUSIONS:
      Gender differences in PWB can be found at the subscale levels of Li's version,
      which exhibits metric and scalar invariance.

PMID- 25959862
TI  - DNA topology influences molecular machine lifetime in human serum.
AB  - DNA nanotechnology holds the potential for enabling new tools for biomedical
      engineering, including diagnosis, prognosis, and therapeutics. However,
      applications for DNA devices are thought to be limited by rapid enzymatic
      degradation in serum and blood. Here, we demonstrate that a key aspect of DNA
      nanotechnology-programmable molecular shape-plays a substantial role in device
      lifetimes. These results establish the ability to operate synthetic DNA devices
      in the presence of endogenous enzymes and challenge the textbook view of near
      instantaneous degradation. 

PMID- 25959863
TI  - Bringing cohort studies to the bedside: framework for a 'green button' to support
      clinical decision-making.
AB  - When providing care, clinicians are expected to take note of clinical practice
      guidelines, which offer recommendations based on the available evidence. However,
      guidelines may not apply to individual patients with comorbidities, as they are
      typically excluded from clinical trials. Guidelines also tend not to provide
      relevant evidence on risks, secondary effects and long-term outcomes. Querying
      the electronic health records of similar patients may for many provide an
      alternate source of evidence to inform decision-making. It is important to
      develop methods to support these personalized observational studies at the point
      of-care, to understand when these methods may provide valid results, and to
      validate and integrate these findings with those from clinical trials.

PMID- 25959865
TI  - Damage to the pyramidal tracts is necessary and sufficient for the production of
      the pyramidal syndrome in man.
AB  - The causal role played by damage to the pyramidal tracts in the production of
      spastic hemiplegia in man has been hotly debated over the past hundred years. Two
      broad streams of thought have emerged from this dispute. The first, which is
      grounded on the clinicopathological schools of Jean-Martin Charcot (1825-1893)
      and Paul Flechsig (1847-1929), claimed that the four cardinal signs of
      hemiplegia, namely (i) paralysis, (ii) spasticity, (iii) hyperactive phasic
      muscle reflexes ("tendon jerks") and (iv) the sign of Babinski, are caused by
      injury or dysfunction of the pyramidal tracts. The second school, championed by
      John Farquhar Fulton (1899-1960) and Derek Denny-Brown (1901-1981), reflects the
      increasing influence of experimental neurology on clinicopathological concepts
      after World War II. According to this school, most elements of the pyramidal
      syndrome are caused by the added release or injury of extrapyramidal structures
      at different levels of the forebrain and brainstem. Most symptoms of spastic
      hemiplegia were thus interpreted as signs of extrapyramidal (e.g.,
      reticulospinal) release or damage. However, consensus on which symptoms of
      spastic hemiplegia were due to pyramidal or extrapyramidal changes was never
      reached. To add to this uncertainty, a number of clinicopathological cases that
      supported the old view were sporadically published over the same period. The
      purpose of the present essay is to provide clinicoanatomic perspective to the
      neurological literature in support of the hypothesis that damage to the pyramidal
      tracts is a necessary and sufficient condition for the production of the complete
      pyramidal syndrome in man. 

PMID- 25959864
TI  - Nuclear EGFR characterize still controlled proliferation retained in better
      differentiated clear cell RCC.
AB  - Renal cell carcinoma (RCC) is the most common solid kidney tumor representing 2
      3% of all cancers, with the highest frequency occurring in Western countries.
      There was a worldwide and European annual increase in incidence of approximately
      2% although incidence has been stabilized in last few years. One third of the
      patients already have metastases in the time of the diagnosis with poor prognosis
      because RCC are radio and chemoresistant. The prognostic value of EGFR over
      expression in RCC is a controversial issue that could be explained by different
      histological types of study tumors and non-standardized criteria for evaluation
      of expression. Recent evidences points to a new mode of EGFR signaling pathway in
      which activated EGFR undergoes nuclear translocalization and then, as
      transcription factor, mediates gene expression and other cellular events required
      for highly proliferating activities. According to our observations, the
      membranous expression of EGFR associates with high nuclear grade and poor
      differentiated tumors. On the other hand, nuclear EGFR expression was high in low
      nuclear graded and well differentiated tumors with good prognosis. We hypothesize
      that this mode of EGFR signaling characterizes still controlled proliferation
      retained in well differentiated RCC with Furhman nuclear grade I or II. 

PMID- 25959866
TI  - Optimization of the surface properties of nanostructured Ni-W alloys on steel by
      a mixed silane layer.
AB  - Ni-W nanostructured coatings electrodeposited on steel by galvanostatic pulses
      were functionalized by tetraethoxysilane (TEOS) and octadecyltrichlorosilane
      (OTS) in a two-step procedure. A silica-rich layer is formed by the reaction of
      TEOS with the metal coating surface oxides, which allows a further reaction with
      OTS forming a hydrocarbon-silica outer network. This mixed silane layer provides
      hydrophobicity and improves the corrosion behavior of the Ni-W surface coatings
      without modifying their excellent mechanical properties. 

PMID- 25959867
TI  - Two types of Cassie-to-Wenzel wetting transitions on superhydrophobic surfaces
      during drop impact.
AB  - Despite the fact that superhydrophobic surfaces possess useful and unique
      properties, their practical application has remained limited by durability
      issues. Among those, the wetting transition, whereby a surface gets impregnated
      by the liquid and permanently loses its superhydrophobicity, certainly
      constitutes the most limiting aspect under many realistic conditions. In this
      study, we revisit this so-called Cassie-to-Wenzel transition (CWT) under the
      broadly encountered situation of liquid drop impact. Using model hydrophobic
      micropillar surfaces of various geometrical characteristics and high speed
      imaging, we identify that CWT can occur through different mechanisms, and at
      different impact stages. At early impact stages, right after contact, CWT occurs
      through the well established dynamic pressure scenario of which we provide here a
      fully quantitative description. Comparing the critical wetting pressure of
      surfaces and the theoretical pressure distribution inside the liquid drop, we
      provide not only the CWT threshold but also the hardly reported wetted area which
      directly affects the surface spoiling. At a later stage, we report for the first
      time to our knowledge, a new CWT which occurs during the drop recoil toward
      bouncing. With the help of numerical simulations, we discuss the mechanism
      underlying this new transition and provide a simple model based on impulse
      conservation which successfully captures the transition threshold. By shedding
      light on the complex interaction between impacting water drops and surface
      structures, the present study will facilitate designing superhydrophobic surfaces
      with a desirable wetting state during drop impact. 

PMID- 25959869
TI  - Prediction of fluoroscopic angulation and coronary sinus location by CT in the
      context of transcatheter mitral valve implantation.
AB  - BACKGROUND: We sought to determine if preprocedural CT can predict appropriate
      fluoroscopic angulations to achieve a coplanar view during transcatheter mitral
      valve implantation (TMVI) and to assess the relationship of the mitral annulus
      and the coronary sinus to determine the feasibility of using this as an
      additional landmark on fluoroscopy. METHODS: With CT, the mitral annulus was
      segmented in 25 patients with functional mitral regurgitation. After this,
      optimal projection curves were plotted and the necessary angulations for specific
      views parallel to the trigone-to-trigone line (TT view) and septal-to-lateral
      distance (SL view) were noted. The outer contour of the coronary sinus and great
      cardiac vein were segmented to simulate a guide wire, and its relation to the
      annular plane was assessed. Employed angulations and coplanarity of device
      depiction were investigated in 4 patients who underwent TMVI. RESULTS: The mitral
      annulus is oriented in an anterior superior fashion with tilting to the right. SL
      and TT views were found at 29.4 +/- 9.0 degrees  right anterior oblique (RAO),
      20.1 +/- 8.7 degrees  cranial (CAU) and 81.6 +/- 18.9 degrees  RAO, 56.7 +/- 8.0
      degrees  caudal (CAU). The optimal projection curve and the relationship of
      coronary sinus to the mitral annular plane showed a wide intersubject
      variability. Commonly, the coronary sinus passed along the atrial wall with a
      mean distance of 13.2 +/- 3.7 mm toward the mitral annular plane at P2 and 1.4 +/
      3.1 mm anteriorly in alignment with the TT line. Coplanar depiction of the TMVI
      prosthesis was achieved in all 4 patients, with a compromise view chosen on the
      optimal projection curve between the TT view and SL view. CONCLUSION: CT allows
      for prediction of optimal fluoroscopic angulations to achieve a coplanar view of
      the mitral annulus. The relationship of the coronary sinus to the mitral annulus
      is variable and preprocedural CT segmentation may allow for a more patient
      specific approach to the use of a coronary sinus guide wire as a fluoroscopic
      landmark.

PMID- 25959870
TI  - President's page--The promise of coronary CT angiography: precision medicine.

PMID- 25959868
TI  - Yes-Associated Protein is up-regulated by mechanical overload and is sufficient
      to induce skeletal muscle hypertrophy.
AB  - Mechanically-induced skeletal muscle growth is regulated by mammalian/mechanistic
      target of rapamycin complex 1 (mTORC1). Yes-Associated Protein (YAP) is a
      mechanically-sensitive, and growth-related, transcriptional co-activator that can
      regulate mTORC1. Here we show that, in skeletal muscle, mechanical overload
      promotes an increase in YAP expression; however, the time course of YAP
      expression is markedly different from that of mTORC1 activation. We also show
      that the overexpression of YAP induces hypertrophy via an mTORC1-independent
      mechanism. Finally, we provide preliminary evidence of possible mediators of YAP
      induced hypertrophy (e.g. increased MyoD and c-Myc expression, and decreased
      Smad2/3 activity and muscle ring finger 1 (MuRF1) expression). 

PMID- 25959871
TI  - Why Is Left Atrial Appendage Morphology Related to Strokes? An Analysis of the
      Flow Velocity and Orifice Size of the Left Atrial Appendage.
AB  - BACKGROUND: A specific morphology of left atrial appendage (LAA) has been
      reported to be related to stroke in nonvalvular atrial fibrillation (AF)
      patients. However, the mechanism is not completely understood. This study
      evaluated whether a specific LAA morphology was related to stroke, and whether it
      was related to the change of flow velocity and size of LAA in AF patients.
      METHODS: The morphology, size, and flow velocity of LAA were evaluated in AF
      patients with ischemic strokes (stroke, n = 160) and age-matched AF patients
      without ischemic strokes (control, n = 200). RESULTS: Compared with control, the
      stroke group had a larger LA dimension (4.5 +/- 0.7 vs. 4.2 +/- 0.6 cm, P <
      0.001), larger LAA orifice area (5.3 +/- 2.1 vs. 4.1 +/- 1.7 cm2 , P < 0.001),
      and slower LAA flow velocity (37 +/- 19 vs. 51 +/- 20 cm/s, P < 0.001). The
      stroke group had the chicken wing type less frequently than the control (34% vs.
      50%, P = 0.003). After an adjustment for multiple potential confounding factors,
      the chicken wing type LAA had a decreased stroke risk (odds ratio 0.34, 95%
      confidence interval 0.14-0.84, P = 0.020). Patients with a chicken wing LAA had a
      smaller LAA orifice area (4.4 +/- 1.6 vs. 4.9 +/- 2.2 cm2 , P = 0.013) and higher
      LAA velocity (55 +/- 19 vs. 41 +/- 20 cm/s, P < 0.001) than those with non
      chicken wing LAA. CONCLUSION: A chicken wing type of LAA was related to the less
      incidence of stroke. Our results suggest that the relationship between a specific
      LAA morphology and stroke might be partially explained by the change of the size
      and flow velocity of LAA.

PMID- 25959872
TI  - What the neighbours say.

PMID- 25959873
TI  - Performance Enhancement of Polymer Solar Cells by Using Two Polymer Donors with
      Complementary Absorption Spectra.
AB  - Performance enhancement of polymer solar cells (PSCs) is achieved by expanding
      the absorption of the active layer of devices. To better match the spectrum of
      solar radiation, two polymers with different band gaps are used as the donor
      material to fabricate ternary polymer cells. Ternary blend PSCs exhibit an
      enhanced short-circuit current density and open-circuit voltage in comparison
      with the corresponding HD-PDFC-DTBT (HD)- and DT-PDPPTPT (DPP)-based binary
      polymer solar cells, respectively. Ternary PSCs show a power conversion
      efficiency (PCE) of 6.71%, surpassing the corresponding binary PSCs. This work
      demonstrates that the fabrication of ternary PSCs by using two polymers with
      complementary absorption is an effective way to improve the device performance. 

PMID- 25959875
TI  - Zygomatic Complex Change After Reduction Malarplasty and Its Geometric Model: A
      Retrospective Clinical Study.
AB  - PURPOSE: To achieve optimal outcomes in reduction malarplasty, the amount of
      removed zygomatic bone must be planned accurately. This study aimed to analyze
      the associations between the width of bony resection and changes in zygomatic
      bony parameters, to propose a geometric model to guide surgical planning, and to
      objectively evaluate the surgical outcomes of reduction malarplasty based on
      computed tomographic (CT) images. PATIENTS AND METHODS: This was a retrospective
      observational study of patients who underwent reduction malarplasty. Digitized CT
      images were used to evaluate the bony parameters of the zygomatic complex. A
      geometric model was proposed to guide surgical planning for malar reduction. The
      primary predictor variable was the width of the bony segment to be resected. The
      primary outcome variables were changes in malar prominence and attractiveness.
      Other variables included gender, age, and other bony parameters of the zygoma.
      Bivariate correlation analysis and multiple linear regression analyses were
      performed between predictor and outcome variables. Presurgical and postsurgical
      data were analyzed with paired-samples t test to evaluate surgical outcomes.
      Differences were considered statistically significant at a P value less than .05.
      RESULTS: Fifty-one patients who underwent reduction malarplasty with an L-shaped
      osteotomy from 2012 through 2014 were included in the study. Statistical analysis
      showed a significant decrease in malar prominence and increased attractiveness
      between presurgical and postsurgical images (P < .001). The width of bony
      resection was statistically associated with all outcome variables after adjusting
      for potential confounders. CONCLUSIONS: Reduction malarplasty with a modified L
      shaped osteotomy resulted in a notable decrease in malar prominence and a
      statistical decrease in the zygomatic arch width. The amount of bone that must be
      removed from the zygoma to achieve a desired reduction can be calculated with
      geometric equations. The proposed methodology could assist surgical design and
      improve surgical accuracy.

PMID- 25959874
TI  - A controllable aptamer-based self-assembled DNA dendrimer for high affinity
      targeting, bioimaging and drug delivery.
AB  - Targeted drug delivery is important in cancer therapy to decrease the systemic
      toxicity resulting from nonspecific drug distribution and to enhance drug
      delivery efficiency. We have developed an aptamer-based DNA dendritic
      nanostructure as a multifunctional vehicle for targeted cancer cell imaging and
      drug delivery. The multifunctional DNA dendrimer is constructed from functional Y
      shaped building blocks with predesigned base-pairing hybridization including
      fluorophores, targeting DNA aptamers and intercalated anticancer drugs. With
      controllable step-by-step self-assembly, the programmable DNA dendrimer has
      several appealing features, including facile modular design, excellent
      biostability and biocompatibility, high selectivity, strong binding affinity,
      good cell internalization efficiency, and high drug loading capacity. Due to the
      unique structural features of DNA dendrimers, multiple copies of aptamers can be
      incorporated into each dendrimer, generating a multivalent aptamer-tethered
      nanostructure with enhanced binding affinity. A model chemotherapeutic anticancer
      drug, doxorubicin, was delivered via these aptamer-based DNA dendrimers and
      exerted a potent toxicity for target cancer cells (human T cell acute
      lymphoblastic leukemia cell line) with low side effects for the non-target cells
      (human Burkitt's lymphoma cell line). This controllable aptamer-based DNA
      dendrimer is a promising candidate for biomedical applications. 

PMID- 25959876
TI  - Co-Graft of Bone Marrow Stromal Cells and Schwann Cells Into Acellular Nerve
      Scaffold for Sciatic Nerve Regeneration in Rats.
AB  - PURPOSE: The conventional strategy for bridging large nerve defects, namely nerve
      autograft transplantation, results in donor-site morbidity. This detrimental
      consequence currently drives the search for alternatives. The authors used an
      acellular nerve scaffold filled with bone marrow stromal cells (BMSCs) and
      Schwann cells (SCs) to enhance regeneration. MATERIALS AND METHODS: In 60 adult
      rats, a 10-mm sciatic nerve defect was bridged with a nerve autograft (positive
      control), an acellular nerve scaffold (negative control), an acellular nerve
      scaffold with BMSCs (group I), an acellular nerve scaffold with SCs (group II),
      or an acellular nerve scaffold with BMSCs plus SCs (group III). After
      regenerating for 4 and 16 weeks after surgery, nerve regeneration was
      functionally assessed by a walking track analysis. The compound muscle action
      potential (CMAP), nerve conduction velocity (NCV) along regenerated sciatic
      nerves, and gastrocnemius muscle index (GMI) were recorded to assess the
      conduction properties and extent of denervation atrophy. The number of retrograde
      labeled lumbar motor neurons identified by fluorescent dyes in the ipsilateral
      ventral horn and spinal ganglia were counted to assess the regeneration of axons.
      RESULTS: After 4 and 16 weeks, improvement of the sciatic function index of the
      sciatic nerve in group III was statistically greater than that of the negative
      control group, group I, and group II. At 16 weeks after grafting, obvious
      differences in the GMI were found among groups. Group III had a statistical
      increase in GMI compared with the negative control group, group I, and group II.
      The CMAP and NCV measurements showed comparable results at 16 weeks after
      reconstruction: group III had statistically better results compared with the
      negative control group, group I, and group II. Fluorescent dye analysis of the
      retrograde-labeled lumbar motoneurons in the ipsilateral ventral horn and spinal
      ganglia showed that more motor neurons in the ipsilateral ventral horns and
      spinal ganglia were labeled in group III than in the negative control group,
      group I, and group II at 16 weeks after the operation. All results consistently
      showed that when BMSCs and SCs were loaded together in an acellular nerve
      scaffold, functional recovery of the sciatic nerve was enhanced to the greatest
      degree among the 3 cell-treated groups; furthermore, its beneficial effect on
      sciatic injury regeneration was similar to the autograft group, although it never
      exceeded it. CONCLUSIONS: This study is a step forward in the search for an
      alternative to the nerve autograft because it showed that co-grafting of BMSCs
      and SCs into an acellular nerve scaffold enhanced sciatic nerve functional
      recovery in rats. Its beneficial effect on sciatic injury regeneration was
      similar to the autograft group, although it did not exceed it.

PMID- 25959878
TI  - Effects of Collagen Resorbable Membrane Placement After the Surgical Extraction
      of Impacted Lower Third Molars.
AB  - PURPOSE: The use of resorbable collagen membranes (RMs) in the treatment of
      intraosseous defects and deep periodontal pockets on the distal side of a lower
      second molar (L2M) after surgical extraction of an impacted lower third molar
      (L3M) has shown contradictory results. This study evaluated the effects of RM
      placement on the healing of a bone defect distal to an L2M after surgical
      extraction of a horizontal or mesioangular impacted L3M. PATIENTS AND METHODS: A
      parallel-group randomized controlled trial with 2 independent groups of 30
      patients requiring surgical extraction of an L3M was carried out. After
      extraction, patients received an RM (Bio-Gide, Geistlich Pharma AG, Wolhusen,
      Switzerland) or only suture. At the initial checkup and during postoperative
      monitoring at 1, 3, and 6 months, the distal vestibular, distal, and distolingual
      probing depths and distal vestibular attachment level of the L2M were measured.
      RESULTS: Age (control group, 33.8 +/- 6.9 yr; guided tissue regeneration group,
      35.6 +/- 6.3 yr; P = .322) and the number of women (control group, 15 of 29;
      guided tissue regeneration group, 14 of 27; P = .992) were similar in the 2
      groups. The distal vestibular, distal, and distolingual probing depths of the
      L2M, distal vestibular attachment level, distance from the cementoenamel
      junction, and distance from the alveolar crest to the base of the defect showed
      greater improvement 6 months after surgical extraction in the RM group (P < .05).
      CONCLUSIONS: The use of RMs after surgical extraction of mesioangular or
      horizontally impacted L3Ms stimulates bone regeneration, improving the attachment
      level and bone fill distal to the L2M. Likewise, it decreases the distal probing
      depth and results in faster recovery. RM placement after surgical extraction of
      an impacted L3M is recommended because it prevents periodontal defects after L3M
      surgery.

PMID- 25959877
TI  - Intraoperative Blood Loss During Orthognathic Surgery: A Comparison of
      Remifentanil-Based Anesthesia With Sevoflurane or Isoflurane.
AB  - PURPOSE: The aim of the present study was to compare the blood loss with
      remifentanil-based anesthesia with sevoflurane or isoflurane during orthognathic
      surgery. PATIENTS AND METHODS: In this randomized controlled clinical trial, the
      patients who were scheduled for orthognathic surgery were divided into 2 groups:
      the sevoflurane (Sevo) group and isoflurane (Iso) group. Anesthesia was
      maintained using end-tidal concentrations of 1.4% sevoflurane or 0.9% isoflurane.
      Remifentanil was continuously infused at 0.05 to 0.5 MUg/kg/min to maintain the
      mean blood pressure (MBP) at 60 to 65 mm Hg. The intraoperative blood loss was
      compared between the 2 groups. The Student t test for unpaired samples was used
      for statistical analysis. P < .05 was considered statistically significant.
      RESULTS: The study sample included 19 men and 45 women (n = 64). The mean age was
      25 years (range 16 to 50). The intraoperative blood loss tended to be greater in
      the Iso group (n = 32; 4.79 +/- 3.22 mL/kg) than in the Sevo group (n = 32; 4.00
      +/- 1.98 mL/kg). However, the difference between the 2 groups was not
      significant. CONCLUSION: In a comparison of intraoperative blood loss during
      remifentanil-based anesthesia with sevoflurane or isoflurane during orthognathic
      surgery, no difference was observed between the 2 groups.

PMID- 25959879
TI  - Detection of Rare Variant of SS18-SSX1 Fusion Gene and Mutations of Important
      Cancer-Related Genes in Synovial Sarcoma of the Lip: Gene Analyses of a Case and
      Literature Review.
AB  - Synovial sarcoma (SS) accounts for 5 to 10% of soft tissue sarcomas; however,
      intraoral SS is rare. Histopathologically, SS shows a biphasic pattern with
      epithelial and spindle cell components or a monophasic pattern with only spindle
      cells. The precise diagnosis of SS, especially at an unusual site, is often a
      challenge to pathologists and clinical oncologists, because the differential
      diagnosis of SS includes a broad range of tumors, such as soft tissue sarcomas
      and carcinomas. In the present case, the patient was a 50-year-old woman who
      presented with the chief complaint of swelling and a slowly enlarging mass of the
      lower lip in the mucolabial fold region. The mass was covered with intact mucosa
      and intraoral examination showed no malignant findings. The clinical diagnosis
      was a benign tumor and a probable salivary gland tumor. Macroscopically, the
      excised mass also indicated a benign tumor; however, histopathologic findings
      suggested the diagnosis of SS. For definitive diagnosis, genetic analyses were
      performed with conventional polymerase chain reaction and next-generation
      sequencing. As a result, a rare variant of the SS18-SSX1 fusion transcript, which
      could not be identified by routine procedures for genetic diagnosis, was
      detected. In addition, 8 missense mutations of cancer-related genes were
      confirmed. Detection of the fusion transcript is widely used in the diagnosis of
      SS; however, reported cases of transcript variants of each fusion gene type are
      limited. Reports of mutational analysis of cancer-related genes on SS also are
      rare. The accumulation of rare transcript variants and the cytogenetic characters
      of SS are suggested to be necessary for assuming a genetic diagnosis of SS.

PMID- 25959880
TI  - The diagnostic utility of intracranial EEG monitoring for epilepsy surgery in
      children.
AB  - OBJECTIVE: There are limited data on the indications for the use of chronic
      invasive electroencephalography (EEG) monitoring (IEM) for pediatric epilepsy
      surgery. METHODS: We retrospectively studied 102 children who underwent
      intracranial monitoring to map critical cortex, localize the epileptogenic
      region, or resolve divergent findings. We assessed IEM utility based on changes
      to the resection plan following analysis of noninvasive data. RESULTS: IEM was
      judged useful in 87% of cases and had greatest utility for resolving discordant
      data and localizing extratemporal and multilobar epileptogenic zones. IEM data
      were least useful for seizure onset in the temporal lobe and had little utility
      for direct cortical stimulation mapping unless functional magnetic resonance
      imaging (fMRI) revealed atypical language representation or the epileptogenic
      zone was in proximity to critical cortex. SIGNIFICANCE: IEM utility was
      demonstrated for a majority of cases with well-defined indications. The method of
      assessing utility will facilitate multicentric studies toward developing future
      consensus and practice guidelines.

PMID- 25959881
TI  - Telemetric assessment of social and single housing: Evaluation of
      electrocardiographic intervals in jacketed cynomolgus monkeys.
AB  - INTRODUCTION: Proactive efforts to socially house laboratory animals are a
      contemporary, important focus for enhancing animal welfare. Jacketing cynomolgus
      monkeys has been traditionally considered an exclusionary criterion for social
      housing based on unsubstantiated concerns that study conduct or telemetry
      equipment might be compromised. Our objective was to evaluate the effects of
      jacketing naive, adolescent cynomolgus monkeys in different single and social
      housing types based on parallel comparisons of heart rate. METHODS: Eight naive
      cynomolgus monkeys were randomized into pairs and ECG data were collected for 24h
      from each animal in each housing condition using a crossover design. Caging
      paradigms consisted of standard individual, standard pair, quaternary pair (4
      linked cages), and European-style pair housing in non-sequential order varied by
      pair to control for possible time bias. Dosing and blood collection procedures
      were performed to characterize any effects of housing on ECG data during study
      conduct. RESULTS: There was no increase in the incidence of equipment damage in
      pair vs. individually housed animals. Further, animals in all 4 housing paradigms
      showed similar acclimation assessed as heart rate (mean 139-154 beats per
      minute), and maintained similar diurnal rhythms, with an expected slowing of the
      heart rate at night (aggregate lights out HR 110+/-4bpm compared to daytime 146+/
      7bpm). DISCUSSION: This study demonstrates the effects of different social access
      and housing types on the study-naive cynomolgus monkeys during jacketed
      cardiovascular telemetry data collection in a repeat-dose toxicology study
      design. There were no discernible effects of social housing on baseline ECG
      parameters collected via jacketed telemetry, and all animals maintained expected
      diurnal rhythms in all housing settings tested. These data demonstrate that
      cynomolgus monkeys can be socially housed during data collection as a standard
      practice, consistent with global efforts to improve study animal welfare.

PMID- 25959882
TI  - The Diplomate in Safety Pharmacology (DSP) certification scheme.
AB  - As with other professional disciplines there is a growing need from within
      industry as well as global regulatory authorities for implementation of a
      certification process in order to assure that appropriate expertise is developed
      and quality standards are identified for professionals involved in the practice
      of Safety Pharmacology (SP). In order to meet this need, the Safety Pharmacology
      Society (SPS) has developed the Diplomate in Safety Pharmacology (DSP)
      certification process. There are many benefits to certification including
      authentication of the discipline within the overall pharmaceutical community and
      with regulatory authorities. It also encourages participation in SPS activities
      by other professionals (toxicologists, clinicians, academics) who wish to broaden
      their professional expertise. It provides an opportunity for candidates to
      strengthen their fundamental scientific knowledge, and stimulates the sharing of
      data, methods and model development in the form of publications and presentations
      on relevant topics in SP. Accreditation in SP occurs after candidates
      successfully complete a written certification examination conducted at the annual
      SPS meeting. The DSP exam consists primarily of material pertinent to the conduct
      of SP vital function core battery studies (i.e., cardiovascular, respiratory and
      central nervous systems), supplemental SP studies (i.e., renal/urinary,
      gastrointestinal, immunology, and hematology), Regulatory Guidelines (ICH
      Guidelines) as well as relevant cross-functional knowledge (e.g., physiology,
      pharmacology, toxicology, biochemistry, pathology, pharmacokinetics, dosing
      formulation, analytical methods, and statistics). Maintenance of the DSP
      certification results from the accrual of credits which are gained from a range
      of educational and scientific contributions. Eligibility requirements include a
      combination of at least a bachelor degree in science and two years of relevant
      professional SP experience and one poster presentation on a SP topic as first
      author at a recognized major scientific meeting. 

PMID- 25959883
TI  - Psychosocial risk factors for excessive gestational weight gain: A systematic
      review.
AB  - BACKGROUND: Excessive weight gain during pregnancy can have adverse health
      outcomes for mother and infant throughout pregnancy. However, few studies have
      identified the psychosocial factors that contribute to women gaining excessive
      weight during pregnancy. AIM: To review the existing literature that explores the
      impact of psychosocial risk factors (psychological distress, body image
      dissatisfaction, social support, self-efficacy and self-esteem) on excessive
      gestational weight gain. METHODS: A systematic review of peer-reviewed English
      articles using Academic Search Complete, Cumulative Index to Nursing and Allied
      Health Literature, MEDLINE Complete, PsycINFO, Informit, Web of Science, and
      Scopus was conducted. Quantitative studies that investigated psychosocial factors
      of excessive GWG, published between 2000 and 2014 were included. Studies
      investigating mothers with a low risk of mental health issues and normally
      developing foetuses were eligible for inclusion. From the total of 474 articles
      located, 12 articles were identified as relevant and were subsequently reviewed
      in full. FINDINGS: Significant associations were found between depression, body
      image dissatisfaction, and social support with excessive gestational weight gain.
      No significant relationships were reported between anxiety, stress, self
      efficacy, or self-esteem and excessive gestational weight gain. CONCLUSION: The
      relationship between psychosocial factors and weight gain in pregnancy is
      complex; however depression, body dissatisfaction and social support appear to
      have a direct relationship with excessive gestational weight gain. Further
      research is needed to identify how screening for, and responding to, psychosocial
      risk factors for excessive gestational weight gain can be successfully
      incorporated into current antenatal care.

PMID- 25959886
TI  - [Conflicts of interest in public institutions. It will be the network to exercise
      control?].
AB  - The US Centers for Disease Control and Prevention (CDC) launched a health
      awareness campaign soliciting the use of antiviral drug for influenza. The claim
      is not supported by any statement of the Food and Drug Administration, since the
      Agency concluded that oseltamivir "has not been proven to have a positive impact
      on the potential consequences (such as hospitalizations, mortality, or economic
      impact) of seasonal, avian, or pandemic influenza". A feature article published
      in The BMJ has pointed out the fact that some pharmaceutical companies involved
      in production and marketing of antiviral drugs have provided funding to the CDC
      Foundation to support qualitative research into influenza prevention and
      treatment messaging. This incident highlights the need to better manage the
      possible conflicts of interest that may arise in the work of governmental
      agencies, threatening their reputation.The role of the internet can be valuable
      to raise awareness of these issues, even considering the interest that social
      media have fuelled on the debate on the effectiveness and safety of antiviral
      drugs.

PMID- 25959887
TI  - [Pursuing the ethics of integrity in a business context].
AB  - Having placed the phenomenon of corruption in the wider context of the current
      cultural and anthropological crisis and after recalling the ancient roots of the
      phenomenon, the author proposes an itinerary in six stages that is a sort of a
      minimal ethics in view of affirming and rooting ethical behaviors and prevent
      corruption in a business context. The six stages are: professionalism, respect,
      loyalty, honesty, responsibility, integrity. If corruption is a phenomenon of
      personal (cor-ruptum) and collective (cum-rumpere) breaking and disruption, which
      gives birth to duplicity, hidden and not transparent behaviors, integrity, on the
      contrary, is the attitude of fullness and consistency that manifests and produces
      the healthy character of the individual and the group. The author discerns in the
      corruption of the word a basic destructuring element of relational networks and
      also of relations internal to a business organization. He emphasizes the urgency
      of the recovery of an ethics of the word that alone enables the creation or
      reconstitution of trust, which is the necessary foundation for the good
      performance and livability of interpersonal, social, and corporate relations. 

PMID- 25959888
TI  - [Corruption as individual and organizational sinking].
AB  - The article qualifies the nature of psychosociological perspective in analysing
      corruption in organizations. Corruption is analysed as a mental event and social
      conditions of corruption are investigated. In particular six social and
      organizational factors are identified as relevant in determining the diffusion of
      corruption: meaning, work wellbeing, consistency, social recognition,
      reflexivity, social relations. The main hypothesis explored in the article is
      that to take managerial care of the organisational factors above mentioned is a
      strong and active prevention of the risk of corruption. 

PMID- 25959889
TI  - [What kind of training can be suitable to promote integrity within the Public
      Health Service? The experience of the ASL in Modena].
AB  - The aim of this article is to present a training experience on the Italian Law
      "to prevent and contrast corruption in the Public Administration", carried on in
      the Public Health Service of Modena. It has been two years since the Law 190/2012
      was approved, and with this contribution we would like to explore what type of
      training is congruous with the legislator's aims. Necessary, the consulter has
      had to assume the institutional mandate (imposed by the Law), but moreover he
      tried to understand what are the management approaches and organizational
      cultures that derive from it. Therefore, in addition to the "normative code"
      derived from the Law, it was necessary (during the training) to assume a
      "community code" that derives from building alliances and people's sense of
      responsibility. This step was crucial to start speaking of anti-corruption. Due
      to these premises, we assume the idea of a training as a stimulus for changing
      and strengthening capabilities in complex organizational contexts. In this case,
      instead of static, equilibrium and linearity, people's uncertainty and freedom
      prevails; relationships and individuals' identification with organizations is
      weak. Thus, the consulter has to project and develop people's capacity to think
      and to increase knowledge. Here knowledge means understanding problematic
      contexts and not building theoretical models to be applied. This contribution
      would like to prove how it is necessary to develop a knowledge connected to
      people actions and behaviors; it is a co-construct process done with some key-
      individuals in the organization, starting from concrete problems instead of
      abstract subjects. The consulter has used the indications that derives from the
      Law, but he has projected and developed a training system based on information
      and sensitization aimed at powering best practices that already exists in the
      organization. In fact, the key factor of this experience was to take the point of
      view of different professional experiences in the organization and to work on
      case studies that people themselves have proposed on the subjects derived from
      the application of the Law. 

PMID- 25959890
TI  - [Bibliometrics and web use: the birth of altmetrics].
AB  - Counting citations that a research article received by other articles was the
      traditional bibliometric method for the evaluation of a scientific research.
      Citations have been used both to evaluate a scientific paper - usually in
      conjunction with the peer review methods - and to determine the quality of a
      scientific research output. The development of tools even more Web 2.0 oriented
      has profoundly changed the scientific communication process. In this context,
      many web tools have emerged including the so-called "social media" (e-i.,
      Facebook, Twitter). Hence the need for new indicators to measure the influence of
      these tools on the scientific community and the emergence of alternative metrics.
      Altmetrics combines the traditional bibliometrics tool with the use of the web.
      Formulated with the purpose to measure new aspects of scientific production,
      these new metrics are placed in order to complement and supplement the existing
      indicators rather than act as their replacements. 

PMID- 25959891
TI  - [Barriers and facilitators to the implementation of computerized decision support
      systems in Italian hospitals: a grounded theory study].
AB  - INTRODUCTION: Computerized Decision Support Systems (CDSSs) connect health care
      professionals with high-quality, evidence-based information at the point-of-care
      to guide clinical decision-making. Current research shows the potential of CDSSs
      to improve the efficiency and quality of patient care. The mere provision of the
      technology, however, does not guarantee its uptake. This qualitative study aims
      to explore the barriers and facilitators to the use of CDSSs as identified by
      health providers. METHODS: The study was performed in three Italian hospitals,
      each characterized by a different level of familiarity with the CDSS technology.
      We interviewed frontline physicians, nurses, information technology staff, and
      members of the hospital board of directors (n=24). A grounded theory approach
      informed our sampling criteria as well as the data collection and analysis.
      RESULTS: The adoption of CDSSs by health care professionals can be represented as
      a process that consists of six "positionings," each corresponding to an
      individual's use and perceived mastery of the technology. In conditions of low
      mastery, the CDSS is perceived as an object of threat, an unfamiliar tool that is
      difficult to control. On the other hand, individuals in conditions of high
      mastery view the CDSS as a helpful tool that can be locally adapted and
      integrated with clinicians' competences to fulfil their needs. In the first
      positionings, the uptake of CDSSs is hindered by representational obstacles. The
      last positionings, alternatively, featured technical obstacles to CDSS uptake.
      DISCUSSION: Our model of CDSS adoption can guide hospital administrators
      interested in the future integration of CDSSs to evaluate their organizational
      contexts, identify potential challenges to the implementation of the technology,
      and develop an effective strategy to address them. Our findings also allow
      reflections concerning the misalignment between most Italian hospitals and the
      current innovation trends toward the uptake of computerized decision support
      technologies.

PMID- 25959892
TI  - [Birdman, or the dialectics of recognition on Broadway].

PMID- 25959894
TI  - Physical urticaria: Review on classification, triggers and management with
      special focus on prevalence including a meta-analysis.
AB  - BACKGROUND: Physical urticaria (PU) is a subset of chronic urticaria (CU) induced
      by physical stimuli. To date, there is no consensus in the literature on the
      prevalence of PU among patients with CU. OBJECTIVES: Our objective was to review
      the clinical presentation, diagnosis and management of PU and to estimate the
      prevalence of PU in CU patients. METHODS: We performed a narrative review of PU
      and conducted a systemic review and meta-analysis to determine the pooled
      estimates of the prevalence of PU among patients with CU in the literature up to
      September 2014. We searched four databases (PubMed, Ovid MEDLINE and Web of
      Science) of published work for which full text was available in English or
      French. Studies were eligible if they measured the prevalence of PU in adults or
      children with CU worldwide and ineligible if CU cases were not differentiated
      from total urticaria cases. Meta-analysis was conducted using Stata, version 12.0
      (StataCorp, College Station, TX). In addition, the quality and validity of the
      articles included in the meta-analysis was assessed. RESULTS: Ten studies were
      included in our meta-analysis. Sample sizes ranged from 202 to 4157 patients. The
      pooled prevalence estimate of PU including and excluding cholinergic forms among
      all cases of CU were 13.1% (95% CI: 12.5, 13.6) and 14.9% (95% CI: 14.3, 15.7),
      respectively. CONCLUSION: Our results must be viewed with circumspection because
      of the small number of eligible articles and heterogeneity among studies. Even
      so, the results suggest that PU is an important subset of CU and that physicians
      should be aware of this important condition in order to manage patients
      appropriately.

PMID- 25959893
TI  - Structure and mechanism of the T-box riboswitches.
AB  - In most Gram-positive bacteria, including many clinically devastating pathogens
      from genera such as Bacillus, Clostridium, Listeria, and Staphylococcus, T-box
      riboswitches sense and regulate intracellular availability of amino acids through
      a multipartite messenger RNA (mRNA)-transfer RNA (tRNA) interaction. The T-box
      mRNA leaders respond to nutrient starvation by specifically binding cognate tRNAs
      and sensing whether the bound tRNA is aminoacylated, as a proxy for amino acid
      availability. Based on this readout, T-boxes direct a transcriptional or
      translational switch to control the expression of downstream genes involved in
      various aspects of amino acid metabolism: biosynthesis, transport,
      aminoacylation, transamidation, and so forth. Two decades after its discovery,
      the structural and mechanistic underpinnings of the T-box riboswitch were
      recently elucidated, producing a wealth of insights into how two structured RNAs
      can recognize each other with robust affinity and exquisite selectivity. The T
      box paradigm exemplifies how natural noncoding RNAs can interact not just through
      sequence complementarity but can add molecular specificity by precisely
      juxtaposing RNA structural motifs, exploiting inherently flexible elements and
      the biophysical properties of post-transcriptional modifications, ultimately
      achieving a high degree of shape complementarity through mutually induced fit.
      The T-box also provides a proof-of-principle that compact RNA domains can
      recognize minute chemical changes (such as tRNA aminoacylation) on another RNA.
      The unveiling of the structure and mechanism of the T-box system thus expands our
      appreciation of the range of capabilities and modes of action of structured
      noncoding RNAs, and hints at the existence of networks of noncoding RNAs that
      communicate through both, structural and sequence specificity.

PMID- 25959895
TI  - Conscientious Objection in Medicine: Private Ideological Convictions must not
      Supercede Public Service Obligations.

PMID- 25959896
TI  - Acquiring the 12-lead Electrocardiogram: Doing It Right Every Time.

PMID- 25959897
TI  - Discharge Texting: The Evolution of ED Callbacks.

PMID- 25959898
TI  - Pediatric Mock Codes: An Evidence-Informed Focused Pediatric Resuscitation
      Program.

PMID- 25959899
TI  - Choroidal Maps in Different Types of Macular Edema in Branch Retinal Vein
      Occlusion Using Swept-Source Optical Coherence Tomography.
AB  - PURPOSE: To compare choroidal thickness maps of different types of macular edema
      secondary to branch retinal vein occlusion (BRVO) using swept-source optical
      coherence tomography (SS OCT). DESIGN: Retrospective cross-sectional study.
      METHODS: We generated choroidal thickness maps of 55 eyes of 55 patients with
      BRVO using the macular volumetric raster scan protocol of the SS OCT. The
      enrolled eyes were classified into 4 types of macular edema according to the
      captured OCT images: no macular edema (nME, 13 eyes), cystoid macular edema (CME,
      15 eyes), serous retinal detachment (SRD, 12 eyes), and mixed type (CME + SRD, 15
      eyes). The data from normal fellow eyes served as the control. Statistical
      analysis was performed to compare choroidal thickness maps according to the type
      of macular edema. RESULTS: The mean choroidal thicknesses in the control, nME,
      CME, SRD, and mixed-type groups were 205.77 +/- 41.65 MUm, 211.56 +/- 46.34 MUm,
      214.30 +/- 49.21 MUm, 249.18 +/- 43.51 MUm, and 248.05 +/- 49.51 MUm,
      respectively. No statistical difference in choroidal thickness was observed among
      the nME, CME, and control groups, while the SRD and mixed groups showed larger
      choroidal thickness values than the control group (P < .001). No topographic
      feature in the choroidal thickness was observed to vary according to the location
      of BRVO. CONCLUSIONS: The results suggest the choroidal thickness in BRVO varies
      according to the type of macular edema. Among the macular edema groups, choroidal
      thickness was significantly increased in eyes with SRD relative to those without
      SRD, which suggests that increased choroidal thickness may influence the
      development of SRD in BRVO.

PMID- 25959900
TI  - Programmed Synthesis by Stimuli-Responsive DNAzyme-Modified Mesoporous SiO2
      Nanoparticles.
AB  - DNAzyme-capped mesoporous SiO2 nanoparticles (MP SiO2 NPs) are applied as stimuli
      responsive containers for programmed synthesis. Three types of MP SiO2 NPs are
      prepared by loading the NPs with Cy3-DBCO (DBCO=dibenzocyclooctyl), Cy5-N3 , and
      Cy7-N3 , and capping the NP containers with the Mg(2+) , Zn(2+) , and histidine
      dependent DNAzyme sequences, respectively. In the presence of Mg(2+) and Zn(2+)
      ions as triggers, the respective DNAzyme-capped NPs are unlocked, leading to the
      "click" reaction product Cy3-Cy5. In turn, in the presence of Mg(2+) ions and
      histidine as triggers the second set of DNAzyme-capped NPs is unlocked leading to
      the Cy3-Cy7 conjugated product. The unloading of the respective NPs and the time
      dependent formation of the products are followed by fluorescence spectroscopy
      (FRET). A detailed kinetic model for the formation of the different products is
      formulated and it correlates nicely with the experimental results. 

PMID- 25959901
TI  - Biotin-guided anticancer drug delivery with acidity-triggered drug release.
AB  - A novel biotin-guided anticancer drug delivery system, prodrug , consisting of
      biotin, nitrobenzene, and doxorubicin, with acid-triggered drug releasing
      capability was synthesized. Its cellular uptake and anticancer activity are
      selective to the HepG2 cell line over the WI-38 cell line, as revealed by
      fluorescence confocal microscopic experiments and MTT assay. 

PMID- 25959902
TI  - Infrared identification of the Criegee intermediates syn- and anti-CH3CHOO, and
      their distinct conformation-dependent reactivity.
AB  - The Criegee intermediates are carbonyl oxides that play critical roles in
      ozonolysis of alkenes in the atmosphere. So far, the mid-infrared spectrum of
      only the simplest Criegee intermediate CH2OO has been reported. Methyl
      substitution of CH2OO produces two conformers of CH3CHOO and consequently
      complicates the infrared spectrum. Here we report the transient infrared spectrum
      of syn- and anti-CH3CHOO, produced from CH3CHI + O2 in a flow reactor, using a
      step-scan Fourier-transform spectrometer. Guided and supported by high-level full
      dimensional quantum calculations, rotational contours of the four observed bands
      are simulated successfully and provide definitive identification of both
      conformers. Furthermore, anti-CH3CHOO shows a reactivity greater than syn-CH3CHOO
      towards NO/NO2; at the later period of reaction, the spectrum can be simulated
      with only syn-CH3CHOO. Without NO/NO2, anti-CH3CHOO also decays much faster than
      syn-CH3CHOO. The direct infrared detection of syn- and anti-CH3CHOO should prove
      useful for field measurements and laboratory investigations of the Criegee
      mechanism. 

PMID- 25959903
TI  - Surgical treatment of combined posterior root tears of the lateral meniscus and
      ACL tears.
AB  - BACKGROUND: The treatment of anterior cruciate ligament (ACL) rupture complicated
      with posterior lateral meniscus root (PLMR) tears remains controversial. The goal
      of this study was to evaluate clinical outcomes of PLMR tear refixation versus
      left untreated at the time of reconstruction. MATERIAL/METHODS: From August 2001
      to January 2012, 31 patients who undergone repair of PLMR tears were evaluated
      and compared with a matched control group with untreated PLMR tears. Clinical
      evaluation consisted of the Lysholm scale, subjective International Knee
      Documentation Committee (IKDC) questionnaires, and radiographic evaluation with
      MRI. RESULTS: Regarding to the Lysholm score and the subjective questionnaire
      score, there were no statistical difference between the 2 groups. However,
      patients after operative treatment reach higher functional scores and lower rates
      of osteoarthritis (normal: group A, 80%, and group B, 48%, respectively) with
      statistical significance (P<0.05) compared to the matched control group.
      CONCLUSIONS: Surgical and conservative treatment of the PLMR can both effectively
      improve knee function. However, a tendency towards higher functional scores and
      lower rates of osteoarthritis for patients with operative treatment was observed.

PMID- 25959904
TI  - Surveillance or Adjuvant Treatment With Chemotherapy or Radiotherapy in Stage I
      Seminoma: A Systematic Review and Meta-Analysis of 13 Studies.
AB  - OBJECTIVE: Testicular stage I seminoma has a remarkable cure rate with
      orchiectomy alone. The benefit of adjuvant therapy is questionable, and a direct
      comparison with active surveillance is lacking. We performed a meta-analysis to
      evaluate the benefit of adjuvant radiotherapy (RT) or chemotherapy (CT) compared
      with surveillance alone on relapse-free survival (RFS), overall survival (OS),
      and noncancer-related mortality in patients with stage I seminoma. METHODS: We
      performed a systematic search of PubMed, EMBASE, Web of Science, SCOPUS, and the
      Cochrane Register of Controlled Trials. Meta-analysis was performed using the
      fixed- or random-effects models. The primary endpoint was 5-year RFS, and
      secondary endpoints were 5-year OS and 5-year noncancer-related mortality,
      reported as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A
      total of 13 trials (11 retrospective and 2 prospective cohort series), including
      12,075 patients with stage I seminoma, were analyzed. The relapse rates were 3.9%
      versus 14.8% in the adjuvant therapy and surveillance arms, respectively.
      Overall, adjuvant therapy significantly improved 5-year RFS (OR, 0.17; 95% CI,
      0.1-0.29; P < .00001), but not 5-year OS (OR, 1.03; 95% CI, 0.46-2.28; P = .94).
      Mortality due to other causes was not significantly increased with CT or RT.
      CONCLUSIONS: Adjuvant RT and CT reduce recurrence risk by 80% of stage I
      seminoma. However, they do not increase OS or noncancer-related mortality. Both
      treatment options can be offered to patients with stage I seminoma, taking into
      consideration the side effects and high cure rate of testicular cancer at
      relapse.

PMID- 25959905
TI  - Variation in nitrogen use efficiencies on Dutch dairy farms.
AB  - BACKGROUND: On dairy farms, the input of nutrients including nitrogen is higher
      than the output in products such as milk and meat. This causes losses of nitrogen
      to the environment. One of the indicators for the losses of nitrogen is the
      nitrogen use efficiency. In the Dutch Minerals Policy Monitoring Program (LMM),
      many data on nutrients of a few hundred farms are collected which can be
      processed by the instrument Annual Nutrient Cycle Assessment (ANCA, in Dutch:
      Kringloopwijzer) in order to provide nitrogen use efficiencies. RESULTS: After
      dividing the dairy farms (available in the LMM program) according to soil type
      and in different classes for milk production ha(-1) , it is shown that
      considerable differences in nitrogen use efficiency exist between farms on the
      same soil type and with the same level of milk production ha(-1) . CONCLUSION:
      This offers opportunities for improvement of the nitrogen use efficiency on many
      dairy farms. Benchmarking will be a useful first step in this process.

PMID- 25959906
TI  - Impact of corpulence parameters and haemoglobin A1c on metabolic control in type
      2 diabetic patients: comparison of apolipoprotein B/A-I ratio with fasting and
      postprandial conventional lipid ratios.
AB  - BACKGROUND AND OBJECTIVE: The incidence of diabetes co-morbidities could probably
      be better assessed by studying its associations with major corpulence parameters
      and glycaemic control indicators. We assessed the utility of body mass index
      (BMI), waist circumference (WC), and glycosylated haemoglobin (HbA1c) levels in
      metabolic control for type 2 diabetic patients. METHODS: Fasting and postprandial
      blood samples were collected from 238 type 2 diabetic patients aged 57.4+/-11.9
      years. The sera were analysed for glucose, HbA1c, total cholesterol (TC),
      triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), low-density
      lipoprotein cholesterol (LDL-c), and apolipoproteins (apoA-I and apoB). Ratios of
      lipids and apolipoproteins were calculated and their associations with BMI, WC,
      and HbA1c levels were analysed. RESULTS: Our investigation showed increases in
      most fasting and postprandial lipid parameters according to BMI and WC. In men,
      postprandial HDL-c and TG levels were significantly higher (p<0.05) in overweight
      and obese patients, respectively, as well as in patients with abdominal obesity.
      Contrariwise, postprandial TC levels were significantly higher (p<0.01) in
      overweight and abdominal obese women. However, elevations of apoA-I and apoB
      levels were according to BMI and WC in both genders. There was a strong influence
      of BMI, WC, and HbA1c levels on the apoB/apoA-I ratio compared to traditional
      fasting and postprandial lipid ratios in both men and women. The apoB/apoA-I
      ratio was more correlated with postprandial TC/HDL and LDL-c/HDL-c ratios in men
      and with postprandial TG/HDL-c in women. CONCLUSION: The apoB/apoA-I ratio is
      helpful in assessing metabolic risk caused by overall obesity, abdominal obesity
      and impaired glycaemia in type 2 diabetic patients.

PMID- 25959907
TI  - Determinants of Self-Rated Health in Tehran, from Individual Characteristics
      towards Community-Level Attributes.
AB  - INTRODUCTION: It is generally believed that the attributes of shared environment
      affect health of residents beyond the individual risk factors. This study
      investigates some individual and neighborhood characteristics that may affect
      self-rated health (SRH) in Iran. METHODS: Questions were asked about the social
      capital, economic status and SRH of 1,982 citizens from 200 randomly selected
      locations in Tehran. The neighborhood characteristics were assessed by an
      observational checklist. A multilevel model was designed. RESULTS: SRH was
      significantly different between neighborhoods (P-value < 0.001) and between
      economic groups (P-value < 0.001). At the individual level, social capital (SC)
      and being married had a positive association with SRH, while age, being female
      and bad economic statuses were negatively associated with SRH. At the
      neighborhood level, neighborhoods with higher average education were positively
      association with SRH, and living in neighborhoods under construction had a
      negative association with SRH. CONCLUSIONS: These findings highlight the
      importance of shared social and physical environment, as well as individual
      characteristics on health, although the mechanisms may still be controversial.

PMID- 25959908
TI  - Community Interventional Trial (CITFOMIST) of Vitamin D Fortified Versus Non
      fortified Milk on Serum Levels of 25(OH) D in the Students of Tehran.
AB  - BACKGROUND: As prevention of osteoporosis becomes more imperative with the global
      ageing of the population, establishing different measures to fight vitamin D
      deficiency will also become increasingly important. The aim of this study is to
      help assess the efficacy of vitamin D-fortified milk on circulating
      concentrations of 25(OH)D (as the primary outcome), a widely accepted indicator
      of vitamin D status, in Tehran students. Another objective of the protocol is to
      help assess the compliance with fortified dairy in students of different
      socioeconomic classes. METHOD: The cluster-randomized trial (CITFOMIST) is
      conducted on 15- to19-year olds guidance and high school students of both genders
      from different districts of Tehran, in wintertime. The schools enrolled in this
      study are randomly assigned to receive one of the three groups of milk (whole
      milk, milk that contained 600 IU Vit D/1000cc, or milk that contained 1000 IU Vit
      D /1000cc) for a 30-day period. In order to study the effect of vitamin D
      fortified milk on the circulating concentrations of 25(OH) D, a serum vitamin D
      levels are checked in a subgroup before and after the intervention. CONCLUSION:
      There are few data on the efficacy of incremental doses of vitamin D from
      fortified foods among adolescents. This is while developing an optimal model to
      fight vitamin D deficiency needs further research on bone health outcomes and the
      safety of vitamin D-fortified products. The modified version of this protocol
      could be applied in different parts of the country to assess the efficacy of a
      vitamin-D product.

PMID- 25959909
TI  - Relationship between Anemia and Chronic Complications in Chinese Patients with
      Type 2 Diabetes Mellitus.
AB  - AIMS: To evaluate the potential association of anemia with micro- and
      macrovascular complications in Chinese patient with type 2 diabetes mellitus
      (T2DM). METHODS: A total of 1997 patients with T2DM were included in this cross
      sectional study. Patients were defined as anemic, if hemoglobin (Hb) levels were
      < 13 g/dL in males and < 12 g/dL in females. Data on demographics, anthropometric
      parameters, and co-morbidities were extracted for each patient. RESULTS: Twenty
      two percent of T2DM patients (439/1997) had anemia, and those patients with
      higher rates of micro- and macrovascular complications had higher rates of
      anemia. Univariate logistic regression analysis showed that anemia was a risk
      factor of microvascular complications (OR = 1.83, 95% CI: 1.45 - 2.31; P < 0.001)
      and macrovascular complications (OR = 2.10, 95% CI: 1.63 - 2.71; P < 0.001).
      After adjusting for conventional risk factors, anemia remained positively
      associated with microvascular complications (OR = 1.52, 95% CI: 1.17 - 1.99), but
      lost its association with macrovascular complications (OR = 1.01, 95% CI: 0.73 -
      1.41). Anemia was also independently associated with diabetic retinopathy,
      nephropathy, and peripheral neuropathy. CONCLUSIONS: These findings suggest that
      anemia was related to both micro- and macrovascular complications in Chinese
      patients with T2DM, but was only an independent risk factor of microvascular
      complications. Assessment of Hb levels in T2DM patients may help to prevent
      subsequent diabetic micro- and macrovascular complications.

PMID- 25959910
TI  - Mushroom Extracts Induce Human Colon Cancer Cell (COLO-205) Death by Triggering
      the Mitochondrial Apoptosis Pathway and Go/G1-Phase Cell Cycle Arrest.
AB  - BACKGROUND: Functional foods are extensively studied for their cancer preventive
      effects. In the present study, we compared the anti-cancer activity of aqueous
      extracts of three species of mushrooms including: Pleurotus ostreatus (PAE),
      Auricularia polytricha (AAE) and Macrolepiota procera (MAE) on COLO-205 cells.
      METHODS: Various in vitro approaches were performed to investigate the most
      potential mushroom variety that possesses maximum cytotoxic, anti-proliferative
      and apoptosis inducing properties. MTT assay was used to assess cytotoxicity.
      IC50 values were obtained and further used to perform clonogenic survival, wound
      scratch and apoptosis assays. Gene expression studies of apoptosis and cell cycle
      related studies were performed by reverse transcriptase PCR, followed by
      estimation of DNA content by flow cytometric analysis. RESULTS: Our study showed
      that PAE acts as the most prominent inducer of cancer cell death as compared to
      other species. Therefore, we performed expression studies for apoptosis and cell
      cycle to understand the genes which are responsible for their profound
      activities. Expression studies illustrated increased levels of caspase-9 (1 to
      2.1, P < 0.01), caspase-3 (1 to 1.7, P < 0.01) and Bax (1 to 1.4, P < 0.05) genes
      followed by decreased levels of Bcl-2 (1 to 0.44, P < 0.05) gene with PAE
      treatment and this was attributed to the activation of intrinsic pathway. Along
      with apoptosis, an arrest at Go/G1 phase was observed through flow cytometric
      analysis followed by increased expression of inhibitors of cyclin dependent
      kinases (CKIs), p16 (1 to 1.5, P < 0.05) and p21 (1 to 2.4, P < 0.01).
      CONCLUSION: This study exemplifies the effectiveness of PAE and may serve as a
      potential therapeutic agent.

PMID- 25959911
TI  - Prenatal Screening for Aneuploidies Using QF-PCR and Karyotyping: A Comprehensive
      Study in Iranian Population.
AB  - BACKGROUND: We have investigated the efficacy of QF-PCR for the prenatal
      recognition of common aneuploidy and compared our findings with cytogenetic
      results in our laboratories. METHODS: A total of 4058 prenatal samples (4031
      amniotic fluid and 27 chorionic villous samples) were analyzed by QF-PCR using
      several selected STR markers together with amelogenin. Results were compared to
      those obtained by conventional cytogenetic analysis. RESULTS: We detected 139
      (3.42%) numerical abnormalities in our subjects by QF-PCR. Concordant QF-PCR and
      karyotype results were obtained in 4001 (98.59%) of the samples. An abnormal
      karyotype associated with adverse clinical outcome undetected by QF-PCR was found
      in 16.66% (n = 28) of samples. Using QF-PCR alone, we were able to detect
      abnormalities in 98.59% of all referred families; however the karyotyping results
      improved the detection rate to 99.85% of the referred cases. Individuals with
      neonatal screening result with 1:10 risk ratio showed 11.29% abnormal karyotype
      while this number was 2.16% in mothers with risk ratio of 1:250 or less.
      CONCLUSION: In countries where large scale conventional cytogenetic is hampered
      by its high cost and lack of technical expertise, QF-PCR may be used as the first
      line of screening for detection of chromosomal abnormalities. We also recommend
      QF-PCR for all the families that are seeking prenatal diagnosis of single gene
      disorders aneuploidies screening to be added to their work up.

PMID- 25959912
TI  - Detection of Specific Antibodies to HCV-ARF/CORE+1 Protein in Cirrhotic and Non
      Cirrhotic Patients with Hepatitis C: A Possible Association with Progressive
      Fibrosis.
AB  - BACKGROUND: The role of different viral proteins in the progression of the
      disease to cirrhosis is not completely understood. The ARFP/F protein is a newly
      described protein synthesized from the +1 or -2 reading frames of the core
      protein gene, which its function remains unknown. The purpose of this study is to
      detect specific antibodies to HCV-ARF/Core+1 protein in cirrhotic and non
      cirrhotic patients with HCV and investigate any possible association. METHODS:
      ARF/Core+1 recombinant proteins from HCV genotype 1a were expressed in
      Escherichia coli, and purified. Using an enzyme-linked immunosorbent assay, we
      assessed the prevalence of anti-ARF/Core+1 antibodies in 50 cirrhotic and 50 non
      cirrhotic hepatitis C patients. RESULTS: All 50 cirrhotic patients were positive
      for anti-ARF/Core+1 antibody, while only 80% positive samples among non-cirrhotic
      patients were detected. The titer of anti-ARF/Core+1 antibody was also
      significantly higher in patients with cirrhosis than in non-cirrhotic patients.
      CONCLUSION: Compared to 80% positive samples among non-cirrhotic patients all 50
      cirrhotic patients were positive for anti-ARF/Core+1 antibody and titer of anti
      ARF/Core+1 antibody was significantly higher in patients with cirrhosis than in
      non-cirrhotic. These results suggest that ARF/Core+1 protein is associated with
      cirrhosis. A possible causative association between ARF/Core+1 and cirrhosis as
      well as the mechanism of this association needs to be further investigated.

PMID- 25959913
TI  - Rational fluid therapy for sepsis and septic shock; what do recent studies tell
      us?
AB  - Sepsis and septic shock persist as major healthcare challenge, with high
      morbidity and mortality. Fluid management is a large part of the treatment in
      patients with these disorders. Fluid therapy has been an important component of
      the care of patients for the past century. However, recently well-designed
      studies have been published focusing on the impact of the type and amount of
      fluids on important clinical outcomes. This review summarizes all the relevant
      recent studies and attempts to develop a rational approach to the initial fluid
      management of patients with suspected sepsis.

PMID- 25959914
TI  - Prognostic factors of survival rate in oral squamous cell carcinoma: clinical,
      histologic, genetic and molecular concepts.
AB  - Oral squamous cell carcinoma (OSCC) represents 95% of all forms of head and neck
      cancers. The five-year survival rate of OSCC patients has been reported
      approximately 50%, which is not satisfactory despite new treatment modalities.
      The aim of the current review is to present factors (histologic, clinical,
      genetic and molecular biomarkers) correlated with survival rate in OSCC patients.
      A web-based search for all types of articles published was initiated using
      MEDLINE/PubMed. The search was restricted to articles focusing on relevant
      clinical, histologic, genetic and molecular factors of survival rate in OSCC and
      presenting new concepts in this field. Mode of invasion, presence of lymph node
      metastasis, extra-capsular spread, surgical margins and invasive tumor front
      grade are clinical and histologic parameters, which are strongly associated with
      survival rate. Focusing on selected proteins, wide range of molecular markers and
      gene alterations involving in cell cycle regulation, apoptosis, cell migration,
      cell adhesion and tumor microenvironment have been documented. Among well-known
      molecular markers, cyclin dependent kinase, survivin, CD44, BUBR1, and heat shock
      proteins (27,70) can be considered as independent prognostic factors of survival
      rate. The identified prognostic factors imply a relatively comprehensive
      understanding of factors related to survival rate in OSCC patients, and provide
      an additional tool for selecting patients who need more aggressive treatment
      design. 

PMID- 25959915
TI  - Oncocytoma of palatal minor salivary gland.
AB  - Oncocytoma is a rare benign salivary gland tumor, which mostly occurs in the
      parotid gland. In this article, we describe an early onset of oncocytoma of minor
      salivary gland in a 36-year, white male. On clinical examination, we encounter
      with a painless, granular, sessile mass. After Excisional biopsy, the
      histopathological features revealed sheets of cells with abundant granular
      eosinophilic cytoplasm, and large, round nuclei that are known as "Oncocyte". 

PMID- 25959916
TI  - Atresia of the Colon Associated with Hirschsprung's Disease.
AB  - Atresia of the colon is a rare anomaly with an incidence of between 1:20,000 and
      1:66,000 live births being reported. Hirschsprung's disease association with
      Colonic atresia is usually diagnosed after several failures of intestinal
      anastomoses. We herein report one of the first patients in the literature
      diagnosed before a therapeutic challenge. A 2-day-old female was admitted with
      severe abdominal distention, bilious vomiting and failure to pass meconium. A
      distended abdomen accompanied by hypoactive bowel sounds was also observed.
      Abdominal X-ray revealed increased intestinal gas, mainly in the colon. Type IIIa
      atresia of the colon at the level of the splenic flexure was found at laparotomy.
      A temporary double-barrel colostomy was completed, and she was discharged from
      hospital on the tenth day after operation without any complications. At the age
      of 3 months, due to the aspect of the distal colon, a rectal biopsy was performed
      and aganglionosis was confirmed. The combination of intestinal aganglionosis and
      colonic atresia is extremely rare.  The concomitance of colonic atresia and
      aganglionosis is calculated to be in 1 in 10 million live births. Wilson, et al.
      claims that 80 percent of infants with colonic atresia have associated
      gastrointestinal anomalies. These defects include rotation and fixation
      anomalies. However, aganglionosis and intestinal neuronal dysplasia should be
      taken into account as well. When both diseases are combined, the etiology is
      still uncertain and several etiologies have been suggested. The association
      should be suspected in all cases of colonic atresia and rectal biopsies are
      advocated at the primary operation in patients with atresia of the colon. 

PMID- 25959917
TI  - A case of familial Carney complex.
AB  - Carney complex is a syndrome characterized by skin pigmentation abnormalities,
      myxomas, endocrine tumors/overactivity, and schwannomas. It is caused by a
      mutation in the PRKAR1A gene that encodes the enzyme protein kinase A regulatory
      subunit type 1 alpha. A 23-year old male was diagnosed with Carney complex on the
      basis of spotty skin lentigines on his face and lips, multiple thyroid neoplasms,
      a right ventricular myxoma, and bilateral testicular tumors. A total bilateral
      orchectomy was performed and the pathological findings revealed Leydig's cell
      tumors on one side and a Sertoli cell tumor on the other side. When his first
      degree relatives were examined, his mother was found to have Carney complex as
      well. This is the first reported case of familial Carney complex in China. 

PMID- 25959918
TI  - Photoclinic. Chest Wall and Spinal Tuberculous Abscess.

PMID- 25959919
TI  - EVI1, a target gene for amplification at 3q26, antagonizes transforming growth
      factor-beta-mediated growth inhibition in hepatocellular carcinoma.
AB  - EVI1 (ecotropic viral integration site 1) is one of the most aggressive oncogenes
      associated with myeloid leukemia. We investigated DNA copy number aberrations in
      human hepatocellular carcinoma (HCC) cell lines using a high-density
      oligonucleotide microarray. We found that a novel amplification at the
      chromosomal region 3q26 occurs in the HCC cell line JHH-1, and that MECOM (MDS1
      and EVI1 complex locus), which lies within the 3q26 region, was amplified.
      Quantitative PCR analysis of the three transcripts transcribed from MECOM
      indicated that only EVI1, but not the fusion transcript MDS1-EVI1 or MDS1, was
      overexpressed in JHH-1 cells and was significantly upregulated in 22 (61%) of 36
      primary HCC tumors when compared with their non-tumorous counterparts. A copy
      number gain of EVI1 was observed in 24 (36%) of 66 primary HCC tumors. High EVI1
      expression was significantly associated with larger tumor size and higher level
      of des-gamma-carboxy prothrombin, a tumor marker for HCC. Knockdown of EVI1
      resulted in increased induction of the cyclin-dependent kinase inhibitor p15(INK)
      (4B) by transforming growth factor (TGF)-beta and decreased expression of c-Myc,
      cyclin D1, and phosphorylated Rb in TGF-beta-treated cells. Consequently,
      knockdown of EVI1 led to reduced DNA synthesis and cell viability. Collectively,
      our results suggest that EVI1 is a probable target gene that acts as a driving
      force for the amplification at 3q26 in HCC and that the oncoprotein EVI1
      antagonizes TGF-beta-mediated growth inhibition of HCC cells. 

PMID- 25959920
TI  - Catastrophic subarachnoid hemorrhage in eosinophilic granulomatosis with
      polyangiitis without asthma.
AB  - Eosinophilic granulomatosis with polyangiitis (EGPA) is characterized by
      eosinophilic vasculitis. Patients rarely present without asthma. Cases developing
      subarachnoid hemorrhage from central nervous system vasculitis are rarely
      reported. We report a 48-year-old woman with rapidly evolving and progressive
      multi-system eosinophilic vasculitis in the absence of asthma. Tissue
      eosinophilia was apparent in a breast lump biopsy. Prior otitis media and
      prominent lymphoid tissue in the postnasal spaces hinted at otolaryngological
      disease. She had rapid disease progression with mononeuritis multiplex and
      eventually succumbed to complications of intracranial hemorrhage secondary to
      central nervous system vasculitis. This case demonstrates the diagnostic dilemma
      and treatment considerations in EGPA without asthma. It also raises the question
      if a reliable biomarker can aid diagnosis in atypical presentations of disease.

PMID- 25959922
TI  - Tubulin structure-based drug design for the development of novel 4beta-sulfur
      substituted podophyllum tubulin inhibitors with anti-tumor activity.
AB  - The well-characterized anti-tubulin agent, podophyllotoxin (PTOX), with the 4'
      position methoxyl group, targets the colchicines domain located between alpha-
      and beta-tubulin. Two guanosine triphosphate (GTP) analogs of the tubulin-binding
      region were synthesized from PTOX, where a hydroxyl group was substituted with a
      carbon-sulfur bond. These compounds, 4-MP-PTOX and 4-TG-PTOX, reduce the dosage
      and greatly improve the therapeutic effect for microtubule damage in cancer
      cells. Here we characterize the anti-tubulin properties of these compounds. We
      found the stronger inhibition of tubulin polymerization (the concentration of 50%
      growth inhibition, GI50<2 MUM) for compounds 4-TG-PTOX and 4-MP-PTOX, which were
      better than that of PTOX or colchicine. The cytotoxicity of two designed
      compounds on tumor cells was also significantly enhanced by comparing to those of
      PTOX and colchicines. The DeltaH value of 4-MP-PTOX and 4-TG-PTOX binding to
      tubulin by isothermal titration calorimetry (ITC) was found to be -7.4 and -5.3
      kcal.mol(-1), respectively. The wide range of enthalpy values across the series
      may reflect entropy/enthalpy compensation effects. Fragments 6-mercaptopurine
      (MP) and 6-thioguanine (TG) likely enhance the affinity of 4-MP-PTOX and 4-TG
      PTOX binding to tubulin by increasing the number of binding sites. The
      correctness of rational drug design was strictly demonstrated by a bioactivity
      test.

PMID- 25959923
TI  - The functional significance of shyness in anorexia nervosa.
AB  - The defining features of anorexia nervosa (AN) include disordered eating and
      disturbance in the experience of their bodies; however, many women with AN also
      demonstrate higher harm avoidance (HA), lower novelty seeking, and challenges
      with interpersonal functioning. The current study explored whether HA and novelty
      seeking could explain variation in disordered eating and social functioning in
      healthy control women ( n = 18), weight-restored women with a history of AN (n =
      17), and women currently-ill with AN (AN; n = 17). Our results indicated that
      clinical participants (AN + weight-restored women) reported poorer social skills
      than healthy control participants. Moreover, the relationship between eating
      disorder symptoms and social skill deficits was mediated by HA. Follow-up
      analyses indicated that only the 'shyness with strangers' factor of HA
      independently mediated this relationship. Collectively, our results suggest a
      better understanding of shyness in many individuals with eating disorders could
      inform models of interpersonal functioning in AN.

PMID- 25959921
TI  - Is Post-Traumatic Stress Disorder Associated with Premature Senescence? A Review
      of the Literature.
AB  - OBJECTIVE: Post-traumatic stress disorder (PTSD) has major public health
      significance. Evidence that PTSD may be associated with premature senescence
      (early or accelerated aging) would have major implications for quality of life
      and healthcare policy. We conducted a comprehensive review of published empirical
      studies relevant to early aging in PTSD. METHOD: Our search included the PubMed,
      PsycINFO, and PILOTS databases for empirical reports published since the year
      2000 relevant to early senescence and PTSD, including: 1) biomarkers of
      senescence (leukocyte telomere length [LTL] and pro-inflammatory markers), 2)
      prevalence of senescence-associated medical conditions, and 3) mortality rates.
      RESULTS: All six studies examining LTL indicated reduced LTL in PTSD (pooled
      Cohen's d = 0.76). We also found consistent evidence of increased pro
      inflammatory markers in PTSD (mean Cohen's ds), including C-reactive protein =
      0.18, Interleukin-1 beta = 0.44, Interleukin-6 = 0.78, and tumor necrosis factor
      alpha = 0.81. The majority of reviewed studies also indicated increased medical
      comorbidity among several targeted conditions known to be associated with normal
      aging, including cardiovascular disease, type 2 diabetes mellitus,
      gastrointestinal ulcer disease, and dementia. We also found seven of 10 studies
      indicated PTSD to be associated with earlier mortality (average hazard ratio:
      1.29). CONCLUSION: In short, evidence from multiple lines of investigation
      suggests that PTSD may be associated with a phenotype of accelerated senescence.
      Further research is critical to understand the nature of this association. There
      may be a need to re-conceptualize PTSD beyond the boundaries of mental illness,
      and instead as a full systemic disorder.

PMID- 25959924
TI  - Prevention vaginally of HIV-1 transmission in humanized BLT mice and mode of
      antiviral action of polyanionic carbosilane dendrimer G2-S16.
AB  - The development of a safe, effective, and low-priced topical microbicide to
      prevent HIV-1 sexual transmission is urgently needed. The emerging field of
      nanotechnology plays an important role in addressing this challenge. We
      demonstrate that topical vaginal administration of 3% G2-S16 prevents HIV-1JR-CSF
      transmission in humanized (h)-BLT mice in 84% with no presence of HIV-1 RNA and
      vaginal lesions. Second-generation polyanionic carbosilane dendrimer G2-S16 with
      silica core and 16 sulfonate end-groups exerts anti-HIV-1 activity at an early
      stage of viral replication, blocking the gp120/CD4 interaction, acting on the
      virus, and inhibiting the cell-to-cell HIV-1 transmission, confirming its
      multifactorial and non-specific ability. This study represents the first
      demonstration that transmission of HIV-1 can be efficiently blocked by vaginally
      applied G2-S16 in h-BLT mice. These findings provide a step forward in the
      development of G2-S16-based vaginal microbicides to prevent vaginal HIV-1
      transmission in humans. FROM THE CLINICAL EDITOR: HIV infections remain a
      significant problem worldwide and the major route of transmission is through
      sexual activity. In this article, the authors developed an antiviral agent
      containing polyanionic carbosilane dendrimer with silica core and 16 sulfonate
      end-groups. When applied vaginally, this was shown to exert anti-HIV protection.
      These positive findings may offer hope in the fight against the spread of HIV
      epidemic.

PMID- 25959925
TI  - Multifunctional selenium nanoparticles: Chiral selectivity of delivering MDR
      siRNA for reversal of multidrug resistance and real-time biofluorescence imaging.
AB  - Herein, chiral selenium nanoparticles (L-SeNPs/D-SeNPs) modified with a dinuclear
      Ruthenium (II) complex were used to effectively deliver siRNA targeting the MDR1
      gene. In this co-delivery system, the luminescent dinuclear Ruthenium (II)
      complex was developed to act as a gene carrier and anti-tumor drug, while
      offering luminescent imaging to follow the intracellular trafficking.
      Interestingly, Ru@L-SeNPs exhibited a stronger protein and pDNA affinity than
      Ru@D-SeNPs, indicating that chirality may have an effect on pDNA/siRNA binding
      and biocompatibility. Cisplatin-resistant A549R cells treated with Ru@L-SeNPs
      siRNA demonstrated significant downregulation of P-glycoprotein (P-gp)
      expression, resulting in unprecedented enhanced cytotoxicity through the
      induction of apoptosis with the involvement of phosphorylation of p53, MAPK and
      PI3K/Akt signaling pathways. In vivo investigation confirmed that Ru@L-SeNPs
      siRNA nanoparticles exhibited high tumor-targeted fluorescence, enhanced anti
      tumor efficacy, and decreased systemic toxicity. These results suggest that Ru@L
      SeNPs are promising vectors for the delivery of siRNA and for real-time tracking
      of treatment. FROM THE CLINICAL EDITOR: In this study, the authors designed bi
      functional selenium nanoparticles with specific chirality to deliver siRNA, for
      targeting tumor MDR1 gene. The underlying ruthenium (II) complex could also offer
      fluorescence for real-time imaging. This new system has been shown to have
      enhanced efficacy against drug resistant tumor cells in both in-vitro and in-vivo
      experiments.

PMID- 25959926
TI  - Towards early detection of cervical cancer: Fractal dimension of AFM images of
      human cervical epithelial cells at different stages of progression to cancer.
AB  - We used AFM HarmoniX modality to analyse the surface of individual human cervical
      epithelial cells at three stages of progression to cancer, normal, immortal (pre
      malignant) and carcinoma cells. Primary cells from 6 normal strains, 6 cancer,
      and 6 immortalized lines (derived by plasmid DNA-HPV-16 transfection of cells
      from 6 healthy individuals) were tested. This cell model allowed for good control
      of the cell phenotype down to the single cell level, which is impractical to
      attain in clinical screening tests (ex-vivo). AFM maps of physical (nonspecific)
      adhesion are collected on fixed dried cells. We show that a surface parameter
      called fractal dimension can be used to segregate normal from both immortal pre
      malignant and malignant cells with sensitivity and specificity of more than 99%.
      The reported method of analysis can be directly applied to cells collected in
      liquid cytology screening tests and identified as abnormal with regular optical
      methods to increase sensitivity. FROM THE CLINICAL EDITOR: Despite cervical smear
      screening, sometimes it is very difficult to differentiate cancers cells from pre
      malignant cells. By using AFM to analyze the surface properties of human cervical
      epithelial cells, the authors were able to accurately identify normal from
      abnormal cells. This method could augment existing protocols to increase
      diagnostic accuracy.

PMID- 25959927
TI  - Quantitative electrochemical detection of cathepsin B activity in breast cancer
      cell lysates using carbon nanofiber nanoelectrode arrays toward identification of
      cancer formation.
AB  - The proteolytic activity of cathepsin B in complex breast cell lysates has been
      measured with alternating current voltammetry (ACV) using ferrocene (Fc)-labeled
      tetrapeptides immobilized on nanoelectrode arrays (NEAs) fabricated with
      vertically aligned carbon nanofibers (VACNFs). Four types of breast cells have
      been tested, including normal breast cells (HMEC), transformed breast cells (MCF
      10A), breast cancer cells (T47D), and metastatic breast cancer cells (MDA-MB
      231). The detected protease activity was found increased in cancer cells, with
      the MDA-MB-231 metastatic cancer cell lysate showing the highest cathepsin B
      activity. The equivalent cathepsin B concentration in MDA-MB-231 cancer cell
      lysate was quantitatively determined by spiking recombinant cathepsin B into the
      immunoprecipitated MDA-MB-231 lysate and the HMEC whole cell lysate. The results
      illustrated the potential of this technique as a portable multiplex electronic
      device for cancer diagnosis and treatment monitoring through rapid profiling the
      activity of specific cancer-relevant proteases. FROM THE CLINICAL EDITOR: Breast
      cancer is the most common cancer in women. In this report, the authors applied
      the technique of nanoelectrode arrays to try to detect and compare cathepsin B
      activities in normal and breast cancer cells. It was found that protease activity
      correlated positively with the degree of malignancy cancer cells. Taking this
      further, this technique may be useful for rapid diagnosis of cancer in the
      future.

PMID- 25959929
TI  - Obesity and atrial fibrillation: A comprehensive review of the pathophysiological
      mechanisms and links.
AB  - Obesity is a worldwide health problem with epidemic proportions that has been
      associated with atrial fibrillation (AF). Even though the underlying
      pathophysiological mechanisms have not been completely elucidated, several
      experimental and clinical studies implicate obesity in the initiation and
      perpetuation of AF. Of note, hypertension, diabetes mellitus, metabolic syndrome,
      coronary artery disease, and obstructive sleep apnea, represent clinical
      correlates between obesity and AF. In addition, ventricular adaptation, diastolic
      dysfunction, and epicardial adipose tissue appear to be implicated in atrial
      electrical and structural remodeling, thereby promoting the arrhythmia in obese
      subjects. The present article provides a concise overview of the association
      between obesity and AF, and highlights the underlying pathophysiological
      mechanisms. 

PMID- 25959928
TI  - Structural basis for dynamic mechanism of nitrate/nitrite antiport by NarK.
AB  - NarK belongs to the nitrate/nitrite porter (NNP) family in the major facilitator
      superfamily (MFS) and plays a central role in nitrate uptake across the membrane
      in diverse organisms, including archaea, bacteria, fungi and plants. Although
      previous studies provided insight into the overall structure and the substrate
      recognition of NarK, its molecular mechanism, including the driving force for
      nitrate transport, remained elusive. Here we demonstrate that NarK is a
      nitrate/nitrite antiporter, using an in vitro reconstituted system. Furthermore,
      we present the high-resolution crystal structures of NarK from Escherichia coli
      in the nitrate-bound occluded, nitrate-bound inward-open and apo inward-open
      states. The integrated structural, functional and computational analyses reveal
      the nitrate/nitrite antiport mechanism of NarK, in which substrate recognition is
      coupled to the transport cycle by the concomitant movement of the transmembrane
      helices and the key tyrosine and arginine residues in the substrate-binding site.

PMID- 25959930
TI  - Imaging of radiocesium uptake dynamics in a plant body by using a newly developed
      high-resolution gamma camera.
AB  - We developed a new gamma camera specifically for plant nutritional research and
      successfully performed live imaging of the uptake and partitioning of (137)Cs in
      intact plants. The gamma camera was specially designed for high-energy gamma
      photons from (137)Cs (662 keV). To obtain reliable images, a pinhole collimator
      made of tungsten heavy alloy was used to reduce penetration and scattering of
      gamma photons. A single-crystal scintillator, Ce-doped Gd3Al2Ga3O12, with high
      sensitivity, no natural radioactivity, and no hygroscopicity was used. The array
      block of the scintillator was coupled to a high-quantum efficiency position
      sensitive photomultiplier tube to obtain accurate images. The completed gamma
      camera had a sensitivity of 0.83 count s(-1) MBq(-1) for (137)Cs with an energy
      window from 600 keV to 730 keV, and a spatial resolution of 23.5 mm. We used this
      gamma camera to study soybean plants that were hydroponically grown and fed with
      2.0 MBq of (137)Cs for 6 days to visualize and investigate the transport dynamics
      in aerial plant parts. (137)Cs gradually appeared in the shoot several hours
      after feeding, and then accumulated preferentially and intensively in growing
      pods and seeds; very little accumulation was observed in mature leaves. Our
      results also suggested that this gamma-camera method may serve as a practical
      analyzing tool for breeding crops and improving cultivation techniques resulting
      in low accumulation of radiocesium into the consumable parts of plants. 

PMID- 25959931
TI  - Disruption of in vitro endothelial barrier integrity by Japanese encephalitis
      virus-Infected astrocytes.
AB  - Blood-brain barrier (BBB) characteristics are induced and maintained by crosstalk
      between brain microvascular endothelial cells and neighboring cells. Using in
      vitro cell models, we previously found that a bystander effect was a cause for
      Japanese encephalitis-associated endothelial barrier disruption. Brain
      astrocytes, which neighbor BBB endothelial cells, play roles in the maintenance
      of BBB integrity. By extending the scope of relevant studies, a potential
      mechanism has been shown that the activation of neighboring astrocytes could be a
      cause of disruption of endothelial barrier integrity during the course of
      Japanese encephalitis viral (JEV) infection. JEV-infected astrocytes were found
      to release biologically active molecules that activated ubiquitin proteasome,
      degraded zonula occludens-1 (ZO-1) and claudin-5, and disrupted endothelial
      barrier integrity in cultured brain microvascular endothelial cells. JEV
      infection caused astrocytes to release vascular endothelial growth factor (VEGF),
      interleukin-6 (IL-6), and matrix metalloproteinases (MMP-2/MMP-9). Our data
      demonstrated that VEGF and IL-6 released by JEV-infected astrocytes were critical
      for the proteasomal degradation of ZO-1 and the accompanying disruption of
      endothelial barrier integrity through the activation of Janus kinase-2
      (Jak2)/signal transducer and activator of transcription-3 (STAT3) signaling as
      well as the induction of ubiquitin-protein ligase E3 component, n-recognin-1 (Ubr
      1) in endothelial cells. MMP-induced endothelial barrier disruption was
      accompanied by MMP-mediated proteolytic degradation of claudin-5 and ubiquitin
      proteasome-mediated degradation of ZO-1 via extracellular VEGF release.
      Collectively, these data suggest that JEV infection could activate astrocytes and
      cause release of VEGF, IL-6, and MMP-2/MMP-9, thereby contributing, in a
      concerted action, to the induction of Japanese encephalitis-associated BBB
      breakdown. GLIA 2015;63:1915-1932.

PMID- 25959932
TI  - Editorial: Action nursing in an uncaring society?

PMID- 25959933
TI  - Repeated myiasis in a female vulvar squamous cell carcinoma caused by Lucilia
      sericata and Sarcophaga crassipalpis.

PMID- 25959935
TI  - Dignity in surgical care: how little we really know.

PMID- 25959934
TI  - Improving communication and recording cardiopulmonary resuscitation decisions.

PMID- 25959937
TI  - Leading and working in teams.
AB  - This article considers the role of the clinical leader as a team member and
      leader and explores how an understanding of the purpose and functions of teams
      can help doctors work more effectively in the various teams with which they are
      involved. 

PMID- 25959938
TI  - Followership, clinical leadership and social identity.
AB  - This article explores how the concepts of followership, social identity and
      social influence help clinical leaders and followers better understand how
      leadership processes function within and between individuals, teams and complex
      organizations. 

PMID- 25959939
TI  - Towards a better understanding of clinical leadership.
AB  - The effectiveness of leadership is important to everyone, yet leadership is often
      misunderstood and represented as undesirable. There are many theoretical models
      of the virtues which make a good leader, but comparatively little practical
      advice. How well do you understand your ability to influence others? How could
      you improve? 

PMID- 25959940
TI  - A clinician's guide to cardiopulmonary exercise testing 2: test interpretation.
AB  - Data obtained from cardiopulmonary exercise testing offer additional interpretive
      power over conventional exercise tolerance testing. When used correctly, these
      data allow improved clinical decision making in patients with cardiometabolic and
      respiratory disease. 

PMID- 25959941
TI  - Anatomy, classification and treatment of intracapsular hip fractures.
AB  - Hip fractures are increasingly common, given the increasing ageing, osteoporotic
      population with significant medical comorbidities. This review summarizes the
      anatomy of the proximal femur, reviews classification systems and gives
      recommendations for use of each treatment modality. 

PMID- 25959942
TI  - Non-cardiac chest pain: a clinical assessment tool.
AB  - A simple clinical approach to patients presenting with chest pain is outlined,
      which is easily taught and can be quickly applied. This approach was demonstrated
      in a large cohort of patients and this article discusses the characteristics of
      the various diagnostic sub-groups. 

PMID- 25959943
TI  - Laurence O'Shaughnessy: outstanding thoracic surgeon, killed in the retreat to
      Dunkirk.

PMID- 25959944
TI  - Ovarian malignancy revealed by anticoagulation.

PMID- 25959945
TI  - Budd-Chiari syndrome: a rare complication of central venous line placement.

PMID- 25959946
TI  - The pitfalls of oximetry.

PMID- 25959947
TI  - Periorbital subcutaneous emphysema: an unreported presentation of perforated
      duodenal ulcer.

PMID- 25959948
TI  - Sowing the seeds for quality improvement in health care: does the solution lie
      with medical schools?

PMID- 25959950
TI  - Continuous infusion of beta-lactam antibiotics to treat severe sepsis: a waste of
      time or worth the hassle?

PMID- 25959951
TI  - What is histopathology and how to get the most out of your histopathologist.

PMID- 25959952
TI  - Histopathology: improving outcomes in bowel cancer.

PMID- 25959953
TI  - The molecular approach to diagnosis in lung cancer.

PMID- 25959954
TI  - The hospital postmortem: time for a revival.

PMID- 25959955
TI  - Arrhythmogenic right ventricular cardiomyopathy coincided with the cardiac
      fibrosis in the inner muscle layer of the left ventricular wall in a boxer dog.
AB  - A 7-year-old female boxer dog died suddenly without any clinical signs. It was
      suspected that the dog had arrhythmogenic right ventricular cardiomyopathy (ARVC)
      due to ventricular premature complexes and ventricular tachycardia at 3 years of
      age. The final diagnosis of ARVC was confirmed by histological characteristics,
      such as loss of cardiocytes and fibrofatty replacement, occurring in the right
      and left ventricular walls. In the cardiocytes, non-lipid vacuoles were observed.
      Cardiac fibrosis and intimal thickening of the small arteries occurred without
      fatty replacement in the inner muscle layer including the papillary muscles of
      the left ventricular wall. This paper describes the pathomorphological details of
      an ARVC case with coincidental cardiac fibrosis in the inner muscle layer of the
      left ventricular wall. 

PMID- 25959956
TI  - Cylindrical spirals associated with severe congenital muscle weakness and
      epileptic encephalopathy.
AB  - INTRODUCTION: Cylindrical spirals are characteristic muscular inclusions
      consisting of spiraling double-laminated membranes. They are found in
      heterogeneous clinical conditions. METHODS: We obtained muscle biopsies from 2
      young sisters with severe congenital hypotonia, muscle weakness, and epileptic
      encephalopathy, and identified cylindrical spirals. RESULTS: We found an
      association between congenital encephalomyopathy and cylindrical spirals.
      CONCLUSIONS: In this morphological and ultrastructural study, we speculate on the
      origin of these peculiar structures.

PMID- 25959957
TI  - The wide spectrum of disease in rhinologic care.

PMID- 25959958
TI  - Rifins, rosetting, and red blood cells.
AB  - The binding of multiple uninfected erythrocytes to a central malaria parasite
      infected erythrocyte (IE) is called rosetting. Rosetting has been associated with
      severe disease, but its functional significance,and the host receptors and
      parasite ligands involved are only partially known. A recent study, which
      describes yet another piece in this already complex puzzle, provides a welcome
      boost and a broadening of an important malaria research field. 

PMID- 25959959
TI  - BCSH guideline on the clinical use of apheresis procedures: new changes and
      future directions.

PMID- 25959960
TI  - HLA-A allele dropout in sequence-specific oligonucleotide probe typing due to
      intronic polymorphism in the novel A*31:01:02:02 allele.
AB  - HLA-A*31:01:02:02 differs from A*31:01:02 in a single nucleotide mutation at
      intron 3, nucleotide position 1000 (G > A). 

PMID- 25959961
TI  - Photoperiod programs dorsal raphe serotonergic neurons and affective behaviors.
AB  - The serotonergic raphe nuclei of the midbrain are principal centers from which
      serotonin neurons project to innervate cortical and sub-cortical structures. The
      dorsal raphe nuclei receive light input from the circadian visual system and
      indirect input from the biological clock nuclei. Dysregulation of serotonin
      neurotransmission is implicated in neurobehavioral disorders, such as depression
      and anxiety, and alterations in the serotonergic phenotype of raphe neurons have
      dramatic effects on affective behaviors in rodents. Here, we demonstrate that day
      length (photoperiod) during development induces enduring changes in mouse dorsal
      raphe serotonin neurons-programming their firing rate, responsiveness to
      noradrenergic stimulation, intrinsic electrical properties, serotonin and
      norepinephrine content in the midbrain, and depression/anxiety-related behavior
      in a melatonin receptor 1 (MT1)-dependent manner. Our results establish
      mechanisms by which seasonal photoperiods may dramatically and persistently alter
      the function of serotonin neurons.

PMID- 25959962
TI  - Genetic dissection of a regionally differentiated network for exploratory
      behavior in Drosophila larvae.
AB  - An efficient strategy to explore the environment for available resources involves
      the execution of random walks where straight line locomotion alternates with
      changes of direction. This strategy is highly conserved in the animal kingdom,
      from zooplankton to human hunter-gatherers. Drosophila larvae execute a routine
      of this kind, performing straight line crawling interrupted at intervals by pause
      turns that halt crawling and redirect the trajectory of movement. The execution
      of this routine depends solely on the activity of networks located in the
      thoracic and abdominal segments of the nervous system, while descending input
      from the brain serves to modify it in a context-dependent fashion. I used a
      genetic method to investigate the location and function of the circuitry required
      for the different elements of exploratory crawling. By using the Slit-Robo axon
      guidance pathway to target neuronal midline crossing defects selectively to
      particular regions of the thoracic and abdominal networks, it has been possible
      to define at least three functions required for the performance of the
      exploratory routine: (1) symmetrical outputs in thoracic and abdominal segments
      that generate the crawls; (2) asymmetrical output that is uniquely initiated in
      the thoracic segments and generates the turns; and (3) an intermittent
      interruption to crawling that determines the time-dependent transition between
      crawls and turns.

PMID- 25959963
TI  - Root Cap-Derived Auxin Pre-patterns the Longitudinal Axis of the Arabidopsis
      Root.
AB  - During the exploration of the soil by plant roots, uptake of water and nutrients
      can be greatly fostered by a regular spacing of lateral roots (LRs). In the
      Arabidopsis root, a regular branching pattern depends on oscillatory gene
      activity to create prebranch sites, patches of cells competent to form LRs. Thus
      far, the molecular components regulating the oscillations still remain unclear.
      Here, we show that a local auxin source in the root cap, derived from the auxin
      precursor indole-3-butyric acid (IBA), modulates the oscillation amplitude, which
      in turn determines whether a prebranch site is created or not. Moreover,
      transcriptome profiling identified novel and IBA-regulated components of root
      patterning, such as the MEMBRANE-ASSOCIATED KINASE REGULATOR4 (MAKR4) that
      converts the prebranch sites into a regular spacing of lateral organs. Thus, the
      spatiotemporal patterning of roots is fine-tuned by the root cap-specific
      conversion pathway of IBA to auxin and the subsequent induction of MAKR4. 

PMID- 25959964
TI  - Cyclin E deregulation promotes loss of specific genomic regions.
AB  - Cell-cycle progression is regulated by the cyclin-dependent kinase (Cdk) family
      of protein kinases, so named because their activation depends on association with
      regulatory subunits known as cyclins. Cyclin E normally accumulates at the G1/S
      boundary, where it promotes S phase entry and progression by activating Cdk2. In
      normal cells, cyclin E/Cdk2 activity is associated with DNA replication-related
      functions. However, deregulation of cyclin E leads to inefficient assembly of pre
      replication complexes, replication stress, and chromosome instability. In
      malignant cells, cyclin E is frequently overexpressed, correlating with decreased
      survival in breast cancer patients. Transgenic mice deregulated for cyclin E in
      the mammary epithelia develop carcinoma, confirming that cyclin E is an
      oncoprotein. However, it remains unknown how cyclin E-mediated replication stress
      promotes genomic instability during carcinogenesis. Here, we show that
      deregulation of cyclin E causes human mammary epithelial cells to enter into
      mitosis with short unreplicated genomic segments at a small number of specific
      loci, leading to anaphase anomalies and ultimately deletions. Incompletely
      replicated regions are preferentially located at late-replicating domains,
      fragile sites, and breakpoints, including the mixed-lineage leukemia breakpoint
      cluster region (MLL BCR). Furthermore, these regions are characterized by a
      paucity of replication origins or unusual DNA structures. Analysis of a large set
      of breast tumors shows a significant correlation between cyclin E amplification
      and deletions at a number of the genomic loci identified in our study. Our
      results demonstrate how oncogene-induced replication stress contributes to
      genomic instability in human cancer.

PMID- 25959965
TI  - Acetylcholine mediates behavioral and neural post-error control.
AB  - Humans often commit errors when they are distracted by irrelevant information and
      no longer focus on what is relevant to the task at hand. Adjustments following
      errors are essential for optimizing goal achievement. The posterior medial
      frontal cortex (pMFC), a key area for monitoring errors, has been shown to
      trigger such post-error adjustments by modulating activity in visual cortical
      areas. However, the mechanisms by which pMFC controls sensory cortices are
      unknown. We provide evidence for a mechanism based on pMFC-induced recruitment of
      cholinergic projections to task-relevant sensory areas. Using fMRI in healthy
      volunteers, we found that error-related pMFC activity predicted subsequent
      adjustments in task-relevant visual brain areas. In particular, following an
      error, activity increased in those visual cortical areas involved in processing
      task-relevant stimulus features, whereas activity decreased in areas representing
      irrelevant, distracting features. Following treatment with the muscarinic
      acetylcholine receptor antagonist biperiden, activity in visual areas was no
      longer under control of error-related pMFC activity. This was paralleled by
      abolished post-error behavioral adjustments under biperiden. Our results reveal a
      prominent role of acetylcholine in cognitive control that has not been recognized
      thus far. Regaining optimal performance after errors critically depends on top
      down control of perception driven by the pMFC and mediated by acetylcholine. This
      may explain the lack of adaptivity in conditions with reduced availability of
      cortical acetylcholine, such as Alzheimer's disease. 

PMID- 25959966
TI  - Homology of head sclerites in Burgess Shale euarthropods.
AB  - The Cambrian fossil record of euarthropods (extant arachnids, myriapods,
      crustaceans, hexapods) has played a major role in understanding the origins of
      these successful animals and indicates that early ancestors underwent an
      evolutionary transition from soft-bodied taxa (lobopodians) to more familiar
      sclerotized forms with jointed appendages [1-3]. Recent advances in
      paleoneurology and developmental biology show that this major transformation is
      reflected by substantial changes in the head region of early euarthropods, as
      informed by the segmental affinity of the cephalic appendages [1, 4-6]. However,
      data on the implications of this reorganization for non-appendicular exoskeletal
      structures are lacking, given the difficulty of inferring the precise segmental
      affinities of these features. Here, I report neurological remains associated with
      the stalked eyes and "anterior sclerite" in the (middle Cambrian) Burgess Shale
      euarthropods Helmetia expansa and Odaraia alata and provide evidence that these
      features are associated with nerve traces originating from the anterior brain
      region, the protocerebrum. The position of the protocerebral ganglia in
      exceptionally preserved Cambrian euarthropods indicates the homology of the
      anterior sclerite in extinct groups (e.g., fuxianhuiids, bivalved forms,
      artiopodans [7, 8]) and allows new comparisons with the dorsal cephalic plate of
      radiodontans, large nektonic predators whose anterior segmental organization
      bears fundamental similarities to that of Paleozoic lobopodians [1, 6, 9, 10].
      These observations allow reconstruction of the segmental architecture of the head
      region in the earliest sclerotized euarthropods and demonstrate the deep homology
      between exoskeletal features in an evolutionary continuum of taxa with distinct
      types of body organization. 

PMID- 25959967
TI  - Dual effect of wasp queen pheromone in regulating insect sociality.
AB  - Eusocial insects exhibit a remarkable reproductive division of labor between
      queens and largely sterile workers [1, 2]. Recently, it was shown that queens of
      diverse groups of social insects employ specific, evolutionarily conserved
      cuticular hydrocarbons to signal their presence and inhibit worker reproduction
      [3]. Workers also recognize and discriminate between eggs laid by the queen and
      those laid by workers, with the latter being destroyed by workers in a process
      known as "policing" [4, 5]. Worker policing represents a classic example of a
      conflict-reducing mechanism, in which the reproductive monopoly of the queen is
      maintained through the selective destruction of worker-laid eggs [5, 6]. However,
      the exact signals used in worker policing have thus far remained elusive [5, 7].
      Here, we show that in the common wasp, Vespula vulgaris, the pheromone that
      signals egg maternity and enables the workers to selectively destroy worker-laid
      eggs is in fact the same as one of the sterility-inducing queen signals that we
      identified earlier [3]. These results imply that queen pheromones regulate insect
      sociality in two distinct and complementary ways, i.e., by signaling the queen's
      presence and inhibiting worker reproduction, and by facilitating the recognition
      and policing of worker-laid eggs. 

PMID- 25959968
TI  - Phenotypic characterization of speed-associated gait changes in mice reveals
      modular organization of locomotor networks.
AB  - Studies of locomotion in mice suggest that circuits controlling the alternating
      between left and right limbs may have a modular organization with distinct
      locomotor circuits being recruited at different speeds. It is not clear, however,
      whether such a modular organization reflects specific behavioral outcomes
      expressed at different speeds of locomotion. Here, we use detailed kinematic
      analyses to search for signatures of a modular organization of locomotor circuits
      in intact and genetically modified mice moving at different speeds of locomotion.
      We show that wild-type mice display three distinct gaits: two alternating, walk
      and trot, and one synchronous, bound. Each gait is expressed in distinct ranges
      of speed with phenotypic inter-limb and intra-limb coordination. A fourth gait,
      gallop, closely resembled bound in most of the locomotor parameters but expressed
      diverse inter-limb coordination. Genetic ablation of commissural V0V neurons
      completely removed the expression of one alternating gait, trot, but left intact
      walk, gallop, and bound. Ablation of commissural V0V and V0D neurons led to a
      loss of walk, trot, and gallop, leaving bound as the default gait. Our study
      provides a benchmark for studies of the neuronal control of locomotion in the
      full range of speeds. It provides evidence that gait expression depends upon
      selection of different modules of neuronal ensembles. 

PMID- 25959969
TI  - Oscillatory Flow Modulates Mechanosensitive klf2a Expression through trpv4 and
      trpp2 during Heart Valve Development.
AB  - In vertebrates, heart pumping is required for cardiac morphogenesis and altering
      myocardial contractility leads to abnormal intracardiac flow forces and valve
      defects. Among the different mechanical cues generated in the developing heart,
      oscillatory flow has been proposed to be an essential factor in instructing
      endocardial cell fate toward valvulogenesis and leads to the expression of klf2a,
      a known atheroprotective transcription factor. To date, the mechanism by which
      flow forces are sensed by endocardial cells is not well understood. At the onset
      of valve formation, oscillatory flows alter the spectrum of the generated wall
      shear stress (WSS), a key mechanical input sensed by endothelial cells. Here, we
      establish that mechanosensitive channels are activated in response to oscillatory
      flow and directly affect valvulogenesis by modulating the endocardial cell
      response. By combining live imaging and mathematical modeling, we quantify the
      oscillatory content of the WSS during valve development and demonstrate it sets
      the endocardial cell response to flow. Furthermore, we show that an endocardial
      calcium response and the flow-responsive klf2a promoter are modulated by the
      oscillatory flow through Trpv4, a mechanosensitive ion channel specifically
      expressed in the endocardium during heart valve development. We made similar
      observations for Trpp2, a known Trpv4 partner, and show that both the absence of
      Trpv4 or Trpp2 leads to valve defects. This work identifies a major
      mechanotransduction pathway involved during valve formation in vertebrates.

PMID- 25959970
TI  - Role of the subesophageal zone in sensorimotor control of orientation in
      Drosophila larva.
AB  - Chemotaxis is a powerful paradigm to investigate how nervous systems represent
      and integrate changes in sensory signals to direct navigational decisions. In the
      Drosophila melanogaster larva, chemotaxis mainly consists of an alternation of
      distinct behavioral modes: runs and directed turns. During locomotion, turns are
      triggered by the integration of temporal changes in the intensity of the
      stimulus. Upon completion of a turning maneuver, the direction of motion is
      typically realigned toward the odor gradient. While the anatomy of the peripheral
      olfactory circuits and the locomotor system of the larva are reasonably well
      documented, the neural circuits connecting the sensory neurons to the motor
      neurons remain unknown. We combined a loss-of-function behavioral screen with
      optogenetics-based clonal gain-of-function manipulations to identify neurons that
      are necessary and sufficient for the initiation of reorientation maneuvers in
      odor gradients. Our results indicate that a small subset of neurons residing in
      the subesophageal zone controls the rate of transition from runs to turns-a
      premotor function compatible with previous observations made in other
      invertebrates. After having shown that this function pertains to the processing
      of inputs from different sensory modalities (olfaction, vision, thermosensation),
      we conclude that the subesophageal zone operates as a general premotor center
      that regulates the selection of different behavioral programs based on the
      integration of sensory stimuli. The present analysis paves the way for a
      systematic investigation of the neural computations underlying action selection
      in a miniature brain amenable to genetic manipulations. 

PMID- 25959971
TI  - A convergent and essential interneuron pathway for Mauthner-cell-mediated
      escapes.
AB  - The Mauthner cell (M-cell) is a command-like neuron in teleost fish whose firing
      in response to aversive stimuli is correlated with short-latency escapes [1-3]. M
      cells have been proposed as evolutionary ancestors of startle response neurons of
      the mammalian reticular formation [4], and studies of this circuit have uncovered
      important principles in neurobiology that generalize to more complex vertebrate
      models [3]. The main excitatory input was thought to originate from multisensory
      afferents synapsing directly onto the M-cell dendrites [3]. Here, we describe an
      additional, convergent pathway that is essential for the M-cell-mediated startle
      behavior in larval zebrafish. It is composed of excitatory interneurons called
      spiral fiber neurons, which project to the M-cell axon hillock. By in vivo
      calcium imaging, we found that spiral fiber neurons are active in response to
      aversive stimuli capable of eliciting escapes. Like M-cell ablations, bilateral
      ablations of spiral fiber neurons largely eliminate short-latency escapes.
      Unilateral spiral fiber neuron ablations shift the directionality of escapes and
      indicate that spiral fiber neurons excite the M-cell in a lateralized manner.
      Their optogenetic activation increases the probability of short-latency escapes,
      supporting the notion that spiral fiber neurons help activate M-cell-mediated
      startle behavior. These results reveal that spiral fiber neurons are essential
      for the function of the M-cell in response to sensory cues and suggest that
      convergent excitatory inputs that differ in their input location and timing
      ensure reliable activation of the M-cell, a feedforward excitatory motif that may
      extend to other neural circuits. 

PMID- 25959973
TI  - Abundance of common species, not species richness, drives delivery of a real
      world ecosystem service.
AB  - Biodiversity-ecosystem functioning experiments have established that species
      richness and composition are both important determinants of ecosystem function in
      an experimental context. Determining whether this result holds for real-world
      ecosystem services has remained elusive, however, largely due to the lack of
      analytical methods appropriate for large-scale, associational data. Here, we use
      a novel analytical approach, the Price equation, to partition the contribution to
      ecosystem services made by species richness, composition and abundance in four
      large-scale data sets on crop pollination by native bees. We found that abundance
      fluctuations of dominant species drove ecosystem service delivery, whereas
      richness changes were relatively unimportant because they primarily involved rare
      species that contributed little to function. Thus, the mechanism behind our
      results was the skewed species-abundance distribution. Our finding that a few
      common species, not species richness, drive ecosystem service delivery could have
      broad generality given the ubiquity of skewed species-abundance distributions in
      nature. 

PMID- 25959972
TI  - The Canadian Systemic Sclerosis Oral Health Study IV: oral radiographic
      manifestations in systemic sclerosis compared with the general population.
AB  - OBJECTIVE: The aim of this study was to compare oral radiologic abnormalities
      associated with systemic sclerosis (SSc) against abnormalities in the general
      population. STUDY DESIGN: Patients with SSc and healthy controls were enrolled in
      a multi-site cross-sectional study. Included in the radiology examination were a
      panoramic radiograph, four bitewings, and an anterior mandibular periapical
      radiograph. Radiographs were evaluated by two oral and maxillofacial radiologists
      tested for interobserver and intraobserver reliability. Chi-squared tests, Fisher
      exact tests, and Mann Whitney U tests were used to summarize the radiologic
      manifestations of patients and controls. RESULTS: We assessed 163 SSc patients
      and 231 controls. Widening of the periodontal ligament space (PLS) (P < .001),
      with higher percentage of teeth with PLS widening (P < .001), was significantly
      more frequent in patients with SSc than in controls. The most significant
      differences between the two groups were found in the molars and premolars (P <
      .001). Moreover, 26% of the patients with SSc had a periapical PLS greater than
      0.19 mm compared with 13% of the controls (P = .003). Patients with SSc had
      significantly more erosions compared with controls (14.5% vs. 3.6%; P < .001),
      mostly in the condyles (P = .022), coronoid processes (P = .005) and other
      locations (P = .012). CONCLUSION: Patients with SSc had more teeth with PLS
      widening and erosions of the mandible compared with controls.

PMID- 25959974
TI  - Rapid multicomponent relaxometry in steady state with correction of magnetization
      transfer effects.
AB  - PURPOSE: To study the effects of magnetization transfer (MT) on multicomponent T2
      parameters obtained using mcDESPOT in macromolecule-rich tissues and to propose a
      new method called mcRISE to correct MT-induced biases. METHODS: The two-pool
      mcDESPOT model was modified by the addition of an exchanging macromolecule proton
      pool to model the MT effect in cartilage. The mcRISE acquisition scheme was
      developed to provide sensitivity to all pools. An incremental fitting was applied
      to estimate MT and relaxometry parameters with minimized coupling. The
      interaction between MT and relaxometry parameters, efficacy of MT correction, and
      feasibility of mcRISE in vivo were investigated in simulations and in healthy
      volunteers. RESULTS: The MT effect caused significant errors in multicomponent
      T1/T2 values and in fast-relaxing water fraction fF , which is consistent with
      previous experimental observations. fF increased significantly with macromolecule
      content if MT was ignored. mcRISE resulted in a multifold reduction of MT biases
      and yielded decoupled multicomponent T1/T2 relaxometry and quantitative MT
      parameters. CONCLUSION: mcRISE is an efficient approach for correcting MT biases
      in multicomponent relaxometry based on steady state sequences. Improved
      specificity of mcRISE may help to elucidate the sources of the previously
      described high sensitivity of noncorrected mcDESPOT parameters to disease-related
      changes in cartilage and the brain.

PMID- 25959975
TI  - Neuropharmacokinetic evaluation of methotrexate-loaded chitosan nanogels.
AB  - Delivery of the hydrophilic drugs to the brain is still a great challenge for the
      treatment of many CNS-related diseases. Nanogels loaded by methotrexate (MTX)
      were prepared using the ionic gelation method. After intravenous administration
      of surface-modified (SMNs) and unmodified nanogels (UMNs) compared to the free
      drug, the neuropharmacokinetic evaluations were applied mainly by tissue drug
      uptake and graphic estimation of the uptake clearance methods. In optimized
      condition, the particle sizes of UMNs and SMNs were 118.54+/-15.93 nm and
      106.68+/-7.23 nm, respectively. Drug entrapment efficiency and drug loading
      capacity were 61.82+/-6.84%, and 53.68+/-3.09%, respectively. The brain
      concentrations of MTX were shown to be higher in the case of both types of the
      nanogels. There were no significant differences between SMNs and UMNs in terms of
      the brain concentrations and AUCs of brain concentration-time profiles.
      Meanwhile, the brain uptake clearance of the drug loaded in SMNs were
      significantly higher than UMN ones (i.e. about 3- and 1.6-times for the high and
      low MTX doses, respectively). It can be concluded that, while the drug loading in
      both forms of nanogels have a significant increasing effect on the brain
      penetration of MTX, surface treatment of nanogels exerts an additional effect on
      the plasma volume cleared from MTX via brain tissue in time unit.

PMID- 25959976
TI  - The synthesis of carbonyl 2-amino-pyrimidines via tandem regioselective
      heterocyclization of 1,3-diynes with guanidine and selective oxidation.
AB  - A highly efficient one-pot approach for the synthesis of carbonyl 2-amino
      pyrimidines from 1,3-diynes and guanidine in the presence of Cs2CO3 and DMSO has
      been described. In these reactions, 1,3-diynes act as a precursor of buta-1,2,3
      trienes and guanidine serves as the N-C[double bond, length as m-dash]N source
      for the construction of pyrimidines. This methodology proves to be a tandem
      regioselective heterocyclization of 1,3-diynes with guanidine and selective
      oxidation with DMSO. 

PMID- 25959977
TI  - Chiral recognition and atropisomerism in the sevoflurane dimer.
AB  - We have examined the stereoselectivity of molecular recognition between two
      molecules of the anesthetic sevoflurane using broadband rotational spectroscopy.
      The transient axial chirality of sevoflurane is revealed upon the formation of
      the dimer, as two different diastereoisomers made of either homo- or heterochiral
      species are detected in a supersonic jet expansion. The conformational assignment
      was confirmed by the observation of eighteen different isotopologues in natural
      abundance (all possible (13)C's and two (18)O species of the homochiral form).
      The two clusters are formed in practically equal proportions (1.1 : 1), probably
      due to their similar hydrogen bonding topologies. In both clusters the complex is
      stabilized by a primary C-H...O hydrogen bond, assisted by weak C-HF
      interactions. This intermolecular binding regime is characterized by a mixture of
      electrostatic and dispersive interactions, midway between classical hydrogen
      bonds and van der Waals clusters.

PMID- 25959978
TI  - Mouse pancreatic beta cells express MHC class II and stimulate CD4(+) T cells to
      proliferate.
AB  - Type 1 diabetes results from destruction of pancreatic beta cells by autoreactive
      T cells. Both CD4(+) and CD8(+) T cells have been shown to mediate beta-cell
      killing. While CD8(+) T cells can directly recognize MHC class I on beta cells,
      the interaction between CD4(+) T cells and beta cells remains unclear. Genetic
      association studies have strongly implicated HLA-DQ alleles in human type 1
      diabetes. Here we studied MHC class II expression on beta cells in nonobese
      diabetic mice that were induced to develop diabetes by diabetogenic CD4(+) T
      cells with T-cell receptors that recognize beta-cell antigens. Acute infiltration
      of CD4(+) T cells in islets occurred with rapid onset of diabetes. Beta cells
      from islets with immune infiltration expressed MHC class II mRNA and protein.
      Exposure of beta cells to IFN-gamma increased MHC class II gene expression, and
      blocking IFN-gamma signaling in beta cells inhibited MHC class II upregulation.
      IFN-gamma also increased HLA-DR expression in human islets. MHC class II(+) beta
      cells stimulated the proliferation of beta-cell-specific CD4(+) T cells. Our
      study indicates that MHC class II molecules may play an important role in beta
      cell interaction with CD4(+) T cells in the development of type 1 diabetes. 

PMID- 25959979
TI  - Pallidal and caudate volumes correlate with walking function in multiple
      sclerosis.
AB  - BACKGROUND: Walking dysfunction is common in multiple sclerosis (MS). The
      thalamus and basal ganglia seemingly have important associations with walking
      performance. The contribution of these subcortical gray matter (SGM) structures
      for walking dysfunction is poorly understood in MS. PURPOSE: This study examined
      associations among volumes of the thalamus and basal ganglia with walking
      outcomes in MS. METHOD: We enrolled 61 MS patients who underwent brain MRI and
      completed the 6-minute walk (6MW) and timed 25-foot walk (T25FW). Volumes of the
      thalamus, caudate, putamen, and pallidum as well as whole-brain white matter (WM)
      and gray matter (GM) were calculated from 3D T1-weighted structural brain images.
      We examined associations using bivariate correlations (r) and partial
      correlations (pr) that controlled for age, MS clinical course, and whole-brain WM
      and GM volumes. We further performed hierarchical linear regression (HLR) for
      identifying the strongest SGM correlate of walking performance. RESULTS: The 6MW
      and T25FW correlated significantly with volumes of the thalamus (r's=.382 &
      .383), caudate (r's=.388 & .416), pallidum (r's=.457 & .457), and putamen
      (r's=.258 & .293) in bivariate correlations. The 6MW and T25FW remained
      significantly correlated with caudate (pr's=.243 & .312) and pallidum (pr's=.321
      & .345) volumes in partial correlations. Pallidum volume was the strongest SGM
      correlate of 6MW (beta=.39) and T25FW (beta=.40) performance in HLR. CONCLUSION:
      We provide novel evidence of possible SGM structures, particularly the pallidum
      and perhaps caudate, as correlates of walking performance in MS.

PMID- 25959980
TI  - Hemispheric differences in malignant middle cerebral artery stroke.
AB  - BACKGROUND: We recently reported that left versus right hemisphere cerebral
      infarctions patients more frequently have worse outcomes. However our clinical
      experience led us to suspect that the incidence of malignant middle cerebral
      artery infarctions (MMCA) was higher in the right compared to the left
      hemispheric strokes. OBJECTIVE: To determine whether laterality in MMCA stroke is
      an important determinant of stroke sequelae. METHODS: A systematic search was
      performed for publications in PubMed using "malignant middle cerebral artery and
      infarction". A total of 73 relevant studies were abstracted. RESULTS: MMCA
      laterality data were available for 2673 patients, with 1687 (63%) right
      hemispheric involvement, thus right being more commonly associated with MMCA
      (binomial test, p<0.05). While mortality rates were similar, right hemispheric
      MMCA (n=271) had mortality of 31% (n=85) whereas left hemispheric MMCA (n=144)
      had mortality of 36% (n=53), morbidity rates were worse on the right. CONCLUSION:
      MMCA stroke appears to be more common on the right, and this laterality is also
      associated with significantly higher morbidity. Further prospective studies are
      needed to more completely understand the nature of this laterality as well as
      test possible new treatments to reduce mortality and morbidity associated with
      MMCA.

PMID- 25959981
TI  - Blurred lines: Reduced discrimination of gray white junctions observed on CT in
      out-of-hospital cardiac arrest (OHCA) portends poor prognosis.

PMID- 25959982
TI  - Harmonizing CPR evaluation oversight.

PMID- 25959983
TI  - Enhancement of cancer specific delivery using ultrasound active bio-originated
      particles.
AB  - A hybrid multifunctional particle comprising of a microbbule (MB), liposome
      (Lipo), and an Fe ion chelated melanin nanoparticle (MNP(Fe)) was applied for
      ultrasound mediated cancer targeting as a theranostic agent. 

PMID- 25959984
TI  - Primary cutaneous precursor B cell lymphoblastic lymphoma in a child, complicated
      by fatal disseminated varicella zoster virus.
AB  - Precursor B-cell lymphoblastic lymphoma (PBLL) is a rare subtype of childhood non
      Hodgkin lymphoma (NHL). Most lymphoblastic lymphomas have a T-cell
      immunophenotype, but a small distinct proportion is of precursor B-cell origin.
      Skin and bone involvement is seen more commonly in this clinical variant. Primary
      cutaneous PBLL is rare. We describe an 8-year-old girl who presented with an
      asymptomatic nodule on the left upper arm. Histopathological features were
      consistent with pre-B-cell lymphoblastic lymphoma, and staging investigations
      excluded extracutaneous disease, resulting in a diagnosis of primary cutaneous
      PBLL. The child was started on induction chemotherapy, UKALL 2003 regimen B. She
      developed disseminated varicella zoster virus and died despite treatment. We
      discuss previously reported cases of primary cutaneous PBLL and their outcomes. 

PMID- 25959985
TI  - Patient led goal setting in chronic low back pain-What goals are important to the
      patient and are they aligned to what we measure?
AB  - OBJECTIVE: To determine the extent of alignment between clinical outcome measures
      and patient-derived goals for the management of chronic low back pain (cLBP).
      METHODS: A customised, patient-led goal setting intervention was implemented
      facilitated by a physiotherapist, in which participants identified problem areas
      and developed strategies to address them. Patient goals were compared to the most
      commonly used outcome measures in cLBP as well as research outcomes recommended
      by the IMMPACT consortium. RESULTS: From 20 participants, a total of 27 unique
      goals were identified, the most common goal related to physical activity (49%).
      Comparison of participant goals to the most common measures used by
      physiotherapists found none of the goals could be aligned. Comparison of goals
      and domains with IMPACCT outcome domains found 76% of the goals were aligned with
      physical functioning and 16% with emotional functioning. CONCLUSION: This study
      has identified goals important to patients in cLBP, these were varied, and most
      did not correspond with current clinical measures. PRACTICE IMPLICATIONS:
      Clinical outcome measures may not be providing accurate information about the
      success of treatments that are meaningful to the patient. Clinicians should
      consider a collaborative approach with cLBP patients to determine treatment
      interventions that are driven by patient preference.

PMID- 25959986
TI  - Towards informed decisions on breast cancer screening: Development and pilot
      testing of a decision aid for Chinese women.
AB  - OBJECTIVE: To pilot-test a novel, self-use breast cancer (BC) screening decision
      aid (DA) targeting Hong Kong (HK) Chinese women at average risk of BC. METHODS:
      Women were recruited through a population-based telephone survey using random
      digit dialling between October 2013 and January 2014. Eligible participants
      completed our baseline survey and then received the DA by post. Participants
      (n=90) completed follow-up telephone interviews one month later. RESULTS: Most
      participants thought that all/most DA content was presented clearly (86.7%), and
      was useful in helping women make screening-related decisions (88.9%). It also
      achieved its expected impact of improving informed decision-making and increasing
      shared-participation preference without increasing participants' anxiety levels.
      Participants showed a modest non-statistical increase in their screening
      knowledge scores. Older women rated the perceived severity of a BC diagnosis as
      significantly lower, and more educated women reported significantly lower
      perceived anxiety about the disease. CONCLUSION: Our DA appears acceptable and
      feasible for self-use by HK Chinese women who need to make an informed decision
      about BC screening without increasing overall anxiety levels. PRACTICE
      IMPLICATIONS: This study supports the potential of self-use DAs for cancer
      screening-related decision support in a Chinese population.

PMID- 25959988
TI  - A rapid test (STic Expert(r) ) for the diagnosis of heparin-induced
      thrombocytopenia--response to De Cooman and Devreese.

PMID- 25959987
TI  - Sewage pollution: mitigation is key for coral reef stewardship.
AB  - Coral reefs are in decline worldwide, and land-derived sources of pollution,
      including sewage, are a major force driving that deterioration. This review
      presents evidence that sewage discharge occurs in waters surrounding at least 104
      of 112 reef geographies. Studies often refer to sewage as a single stressor.
      However, we show that it is more accurately characterized as a multiple stressor.
      Many of the individual agents found within sewage, specifically freshwater,
      inorganic nutrients, pathogens, endocrine disrupters, suspended solids,
      sediments, and heavy metals, can severely impair coral growth and/or
      reproduction. These components of sewage may interact with each other to create
      as-yet poorly understood synergisms (e.g., nutrients facilitate pathogen growth),
      and escalate impacts of other, non-sewage-based stressors. Surprisingly few
      published studies have examined impacts of sewage in the field, but those that
      have suggest negative effects on coral reefs. Because sewage discharge proximal
      to sensitive coral reefs is widespread across the tropics, it is imperative for
      coral reef-focused institutions to increase investment in threat-abatement
      strategies for mitigating sewage pollution.

PMID- 25959990
TI  - Synthesis and confinement of carbon dots in lysozyme single crystals produces
      ordered hybrid materials with tuneable luminescence.
AB  - The synthesis and confinement of graphitic nanoparticles (carbon dots) in the
      nanoscale solvent channels of cross-linked lysozyme single crystals is used to
      prepare novel biohybrid luminescent materials. Co-sequestration of acridine
      orange within the biohybrid crystals from acidic or neutral solutions yields FRET
      mediated phosphors emitting white or green light, respectively. The results offer
      a route to new types of tuneable multicolour luminescent materials based on
      microcrystalline host-guest energy-transfer systems. 

PMID- 25959991
TI  - An all-copper plasmonic sandwich system obtained through directly depositing
      copper NPs on a CVD grown graphene/copper film and its application in SERS.
AB  - A simple, low-cost, all-copper sandwich system has been obtained through directly
      depositing Cu nanoparticles (NPs) onto a graphene sheet, which has already been
      grown on a Cu foil (Cu-NGF). The new design inherits two key advantages: (1) the
      materials of the NGF coupling system are composed of only cheaper Cu instead of
      Au and Ag, (2) direct fabrication of the system without transferring graphene
      will greatly lower the fabrication cost. More importantly, the Cu-NFG system
      shows a high sensitivity in surface-enhanced Raman scattering (SERS) with the
      highest enhancement factor (EF, over 1.89 * 10(7)) reported to date in Cu
      plasmonic systems. Experimental and theoretical results reveal that the strong EF
      is mainly because of the strong near-field coupling between Cu NPs and Cu films
      at the optimal angle of incidence, opening up a new route for Cu materials in
      SERS applications. 

PMID- 25959989
TI  - Pre-therapy inflammation and coagulation activation and long-term CD4 count
      responses to the initiation of antiretroviral therapy.
AB  - OBJECTIVES: Pre-antiretroviral therapy (ART) inflammation and coagulation
      activation predict clinical outcomes in HIV-positive individuals. We assessed
      whether pre-ART inflammatory marker levels predicted the CD4 count response to
      ART. METHODS: Analyses were based on data from the Strategic Management of
      Antiretroviral Therapy (SMART) trial, an international trial evaluating
      continuous vs. interrupted ART, and the Flexible Initial Retrovirus Suppressive
      Therapies (FIRST) trial, evaluating three first-line ART regimens with at least
      two drug classes. For this analysis, participants had to be ART-naive or off ART
      at randomization and (re)starting ART and have C-reactive protein (CRP),
      interleukin-6 (IL-6) and D-dimer measured pre-ART. Using random effects linear
      models, we assessed the association between each of the biomarker levels,
      categorized as quartiles, and change in CD4 count from ART initiation to 24
      months post-ART. Analyses adjusted for CD4 count at ART initiation (baseline),
      study arm, follow-up time and other known confounders. RESULTS: Overall, 1084
      individuals [659 from SMART (26% ART naive) and 425 from FIRST] met the
      eligibility criteria, providing 8264 CD4 count measurements. Seventy-five per
      cent of individuals were male with the mean age of 42 years. The median
      (interquartile range) baseline CD4 counts were 416 (350-530) and 100 (22-300)
      cells/MUL in SMART and FIRST, respectively. All of the biomarkers were inversely
      associated with baseline CD4 count in FIRST but not in SMART. In adjusted models,
      there was no clear relationship between changing biomarker levels and mean change
      in CD4 count post-ART (P for trend: CRP, P = 0.97; IL-6, P = 0.25; and D-dimer, P
      = 0.29). CONCLUSIONS: Pre-ART inflammation and coagulation activation do not
      predict CD4 count response to ART and appear to influence the risk of clinical
      outcomes through other mechanisms than blunting long-term CD4 count gain.

PMID- 25959992
TI  - [Incidence of puerperal diseases during the first 10 days after foaling in the
      mare].
AB  - OBJECTIVE: The aim of this study was to evaluate the frequency of puerperal
      diseases in breeding mares in the first 10 days after birth by analysing patient
      data. MATERIAL AND METHODS: In a university clinic patient data of 308 breeding
      mares with puerperal disorders which presented within the first 10 days
      postpartum were evaluated over a period of 10 years. A distinction was made
      between diseases which were able to be diagnosed at the first examination and
      diseases which developed during the patient's stay in the clinic. RESULTS: A
      total of 21 diseases were diagnosed, with a retained placenta, lochiometra and
      injuries to the perineum being the most common. Many mares displayed more than
      one disease. Mares with a retained placenta most commonly also presented with
      perineal ruptures, followed by animals who also had lochiometra. Mares suffering
      from lochiometra commonly presented together with a retained placenta and
      injuries as a result of birth. Some of the mares developed further diseases. In
      mares with a retained placenta, this was most commonly lochiometra, followed by
      puerperal laminitis and thrombophlebitis. CONCLUSION AND CLINICAL RELEVANCE: The
      data collection shows that several diseases could relatively frequently be
      diagnosed in mares with puerperal disorders. Therefore, a higher percentage of
      further diseases must be assumed for mares which have a puerperal disease.

PMID- 25959993
TI  - Vitamin D supplementation: a comprehensive review on supplementation for
      tuberculosis prophylaxis.
AB  - Vitamin D plays a large role in the innate immune response against Mycobacterium
      tuberculosis (MTB) infection, activation and progression. Likewise, vitamin D
      deficiency is shown by evidence presented here to be a known risk factor for
      developing both MTB infection and active tuberculosis (TB). This comprehensive
      review discusses the evidence and remaining questions regarding vitamin D
      supplementation as a prophylactic measure in those who are at high risk of MTB
      infection and active TB. Vitamin D supplementation is routinely prescribed for
      osteoporosis prevention; yet, guidelines are lacking for its prescription for TB
      prevention, despite the adverse effects being rare. Policymakers are urged here
      to review the literature and provide urgent guidelines on vitamin D
      supplementation for TB prophylaxis.

PMID- 25959994
TI  - Isolation and Molecular Characterization of Acanthamoeba Strains from Dental
      Units in Costa Rica.
AB  - Free-living amoebae are protozoa widely distributed in nature, which can be found
      in a variety of environments. Four genera are recognized as causal agents of
      infections in humans and animals: Acanthamoeba, Naegleria, Balamuthia, and
      Sappinia. In this study, the presence of Acanthamoeba in dental units was
      determined and the isolates obtained were molecularly characterized;
      osmotolerance and thermotolerance assays were also performed to evaluate
      multiplication under these conditions, frequently associated with pathogenicity.
      The morphological analysis and partial sequencing of the 18S rDNA gene revealed
      the presence of Acanthamoeba genotype T4 in 14% of the units sampled.
      Osmotolerance and thermotolerance tests were positive for more than 80% of the
      isolates. Up to date, this is the first study that reports the detection,
      identification, and genotyping of Acanthamoeba isolated from dental units in
      Costa Rica and even in Latin-America. Further assays to determine the potential
      pathogenicity of these Acanthamoeba isolates are underway. 

PMID- 25959995
TI  - A histogram approach to the quality of fit in sedimentation velocity analyses.
AB  - The quality of fit of sedimentation velocity data is critical to judge the
      veracity of the sedimentation model and accuracy of the derived macromolecular
      parameters. Absolute statistical measures are usually complicated by the presence
      of characteristic systematic errors and run-to-run variation in the stochastic
      noise of data acquisition. We present a new graphical approach to visualize
      systematic deviations between data and model in the form of a histogram of
      residuals. In comparison with the ideally expected Gaussian distribution, it can
      provide a robust measure of fit quality and be used to flag poor models. 

PMID- 25959996
TI  - Retrospective analysis of routine use of a double heat cycle (DHC) during
      radiofrequency segmental ablation (ClosureFAST(TM) ) of saphenous veins.
AB  - BACKGROUND: Recent experimental evidence suggests that increasing energy
      delivered during radiofrequency segmental ablation (RFSA) of varicose veins might
      further improve outcomes. OBJECTIVES: To evaluate occlusion rates and safety of
      the routine use of double heat cycle (DHC) during RFSA of incompetent saphenous
      veins up to 3 years after the initial treatment. METHODS: Retrospective review of
      prospectively collected duplex ultrasound (DUS) and complication rate data of
      successive patients from the Viennese, Lower Austrian and Slovenian regions
      treated for incompetent saphenous veins, followed up on a yearly basis for up to
      3 years after the procedure. RESULTS: Between 2007 and 2011, 258 patients (389
      veins; 322 great saphenous veins (GSV)] had been treated with DHC ClosureFast.
      Patients' return was 46% (122 subjects) 3 years after RFSA [140 GSV and 31 small
      saphenous veins (SSV)] with a mean follow-up time of 24.93 +/- 11.77 months. At
      36 months Kaplan-Meier survival analysis showed the occlusion probability of
      98.6% (95% CI: 1.005-0.966). All SSV were closed. Except for three cases of
      dysaesthesia which disappeared within a year, there have not been major side
      effects. CONCLUSIONS: Results of the retrospective analysis indicate that the
      routine use of DHC during RFSA for incompetent saphenous veins is equally safe
      but potentially more efficacious considering mid-term venous closure rates.

PMID- 25959997
TI  - The scientific basis for patient blood management.
AB  - Patient blood management is an increasingly used term to describe an evidence
      based, multidisciplinary approach to optimising the care of patients who might
      need transfusion. It encompasses measures to avoid transfusion such as anaemia
      management without transfusion, cell salvage and the use of anti-fibrinolytic
      drugs to reduce bleeding as well as restrictive transfusion. It ensures that
      patients receive the optimal treatment, and that avoidable, inappropriate use of
      blood and blood components is reduced. This paper provides an overview of the
      scientific basis for patient blood management with a focus on the increasing
      evidence for restrictive rather than liberal transfusion practice and the use of
      electronic blood ordering and decision support to facilitate its implementation. 

PMID- 25959998
TI  - Alcohol intake may impair bone density and new cementum formation after enamel
      matrix derivative treatment: histometric study in rats.
AB  - BACKGROUND AND OBJECTIVE: Alcohol intake may interfere with bone metabolism;
      however, there is a lack of information about the outcomes of regenerative
      approaches in the presence of alcohol intake. Enamel matrix derivative (EMD) has
      been used in periodontal regenerative procedures resulting in improvement of
      clinical parameters. Thus, the aim of this histomorphometric study is to evaluate
      the healing of periodontal defects after treatment with EMD under the influence
      of alcohol intake. MATERIAL AND METHODS: Twenty Wistar rats were randomly
      assigned to two groups: G1 = alcohol intake (n = 10) and G2 = non-exposed to
      alcohol intake (n = 10). Thirty days after initiation of alcohol intake,
      fenestration defects were created at the buccal aspect of the first mandibular
      molar of all animals from both groups. After the surgeries, the defects of each
      animal were randomly assigned to two subgroups: non-treated control and treated
      with EMD. The animals were killed 21 d later. RESULTS: G1 showed less defect fill
      for non-treated controls. Bone density (BD) and new cementum formation were lower
      for G1 when compared to G2, for EMD-treated and non-treated sites. EMD treatment
      resulted in greater BD and new cementum formation in both groups and defect fill
      was not significantly different between groups in the EMD-treated sites. The
      number of tartrate-resistant acid phosphatase-positive osteoclasts was
      significantly higher in G1 when compared to G2 and in EMD-treated sites of both
      groups. CONCLUSION: Alcohol intake may produce a significant detrimental effect
      on BD and new cementum formation, even in sites treated with EMD. A limited
      positive effect may be expected after EMD treatment under this condition.

PMID- 25959999
TI  - Association between herpes zoster and alopecia areata: A population-based study.

PMID- 25960000
TI  - Drug nanosuspensions: a ZIP tool between traditional and innovative
      pharmaceutical formulations.
AB  - INTRODUCTION: A nanosuspension or nanocrystal suspension is a versatile
      formulation combining conventional and innovative features. It comprises 100%
      pure drug nanoparticles with sizes in the nano-scale range, generally stabilized
      by surfactants or polymers. Nanosuspensions are usually obtained in liquid media
      with bottom-up and top-down methods or by their combination. They have been
      designed to enhance the solubility, the dissolution rate and the bioavailability
      of drugs via various administration routes. Due to their small sizes,
      nanosuspensions can be also considered a drug delivery nanotechnology for the
      preparation of nanomedicine products. AREAS COVERED: This review focuses on the
      state of the art of the nanocrystal-based formulation. It describes theory
      characteristics, design parameters, preparation methods, stability issues, as
      well as specific in vivo applications. Innovative strategies proposed to obtain
      nanomedicine formulation using nanocrystals are also reported. EXPERT OPINION:
      Many drug nanodelivery systems have been developed to increase the
      bioavailability of drugs and to decrease adverse side effects, but few can be
      industrially manufactured. Nanocrystals can close this gap by combining
      traditional and innovative drug formulations. Indeed, they can be used in many
      pharmaceutical dosage forms as such, or developed as new nano-scaled products.
      Engineered surface nanocrystals have recently been proposed as a dual strategy
      for stability enhancement and targeting delivery of nanocrystals.

PMID- 25960002
TI  - Effect of Ultrasonic Activation of Irrigants on Smear Layer Removal.
AB  - INTRODUCTION: The objective of this study was to evaluate the efficacy of passive
      ultrasonic irrigation (PUI) with 17% EDTA and 1% NaOCl solutions on smear layer
      removal. METHODS: Root canal preparations of 32 human teeth were performed with
      the ProTaper system. Next, they were longitudinally fractured to permit
      quantitation of smear layer creation from the cervical, middle, and apical thirds
      of the roots by using scanning electron microscopy. After reassembling the
      fractured tooth halves, they were divided into 4 groups according to different
      final irrigation protocols: group1, EDTA + NaOCl; group 2, EDTA with PUI + NaOCl;
      group 3, EDTA + NaOCl with PUI; and group 4, EDTA + NaOCl, both with PUI. After
      irrigation, the tooth halves were separated to permit imaging the same areas by
      scanning electron microscopy, and a percentage of opened dentinal tubules in
      irrigated areas as a percent of the total area was obtained. The results were
      submitted to Kruskal-Wallis, analysis of variance, and Bonferroni tests (alpha =
      0.05). RESULTS: The cervical third of the samples from all groups showed higher
      percentage of smear layer removal and open dentinal tubule areas, followed by the
      middle and apical thirds. Among the irrigation groups, there were statistically
      significant differences in cervical third between group 2 and group 4 samples,
      with the highest and lowest percentage of smear layer removal, respectively.
      CONCLUSIONS: PUI by using 1% NaOCl and ultrasonic tip placed within 1 mm of the
      apical foramen did not show higher efficacy in smear layer removal compared with
      conventional irrigation.

PMID- 25960001
TI  - Structure and mechanism of an antibiotics-synthesizing 3-hydroxykynurenine C
      methyltransferase.
AB  - Streptosporangium sibiricum SibL catalyzes the methyl transfer from S
      adenosylmethionine (SAM) to 3-hydroxykynurenine (3-HK) to produce S
      adenosylhomocysteine (SAH) and 3-hydroxy-4-methyl-kynurenine for sibiromycin
      biosynthesis. Here, we present the crystal structures of apo-form Ss-SibL, Ss
      SibL/SAH binary complex and Ss-SibL/SAH/3-HK ternary complex. Ss-SibL is a
      homodimer. Each subunit comprises a helical N-terminal domain and a Rossmann-fold
      C-terminal domain. SAM (or SAH) binding alone results in domain movements,
      suggesting a two-step catalytic cycle. Analyses of the enzyme-ligand interactions
      and further mutant studies support a mechanism in which Tyr134 serves as the
      principal base in the transferase reaction of methyl group from SAM to 3-HK. 

PMID- 25960003
TI  - The influence of source molecule structure on the low temperature growth of
      nitrogen-doped graphene.
AB  - Doping of heteroatoms such as nitrogen into the lattice structure of graphene can
      tune and tailor the overall electronic properties. N-doped graphene, depending on
      the nitrogen bonding mode and/or bonding configuration, displays subtly altered
      properties in comparison to pristine graphene. However, there remains a
      disappointing shortage of reliable methods for introducing dopants in a
      controlled and reproducible manner, preventing a thorough understanding of the
      relationship between structure and properties. In this study we aimed to prepare
      graphenes with nitrogen atoms doped at a graphitic (quaternary) site by
      depositing a source molecule containing a graphitic nitrogen atom: 4,4,8,8,12,12
      hexamethyl-8,12-dihydro-4H-benzo[9,1]quinolizino[3,4,5,6,7-defg]acridine or 4H
      benzo[9,1]quinolizino[3,4,5,6,7-defg]acridine-4,8,12-trione, on a heated Pt(111)
      substrate. At 400  degrees C, graphene with nitrogen atoms exclusively doped at a
      graphitic site was synthesized from the former molecule, while not from the
      latter molecule at any temperature. The present result indicates that the
      rational design of a source molecule is quite important for controlling the
      nitrogen doped site in the graphene lattice. 

PMID- 25960004
TI  - The role of ammonia oxide in the reaction of hydroxylamine with carboxylic
      esters.
AB  - Theoretical calculations indicate that hydroxylamine can exist in both neutral
      and zwitterionic (ammonia oxide) forms in aqueous solution, the former being 3.5
      kcal mol(-1) more stable. In this report, we have studied the reaction mechanism
      of hydroxylamine with phenyl acetate and analyzed the role of the zwitterionic
      isomer. We have observed that the main reaction pathway takes place through the
      zwitterionic form with a concerted mechanism, not involving the classical
      tetrahedral intermediate. Attack by the nitrogen atom (via neutral isomer) has a
      minor contribution and it is also a concerted process. The activation free energy
      barriers in aqueous solution were calculated at the MP4/TZVPP + diff level for
      gas phase energies, CPCM for optimization and frequencies, and through single
      point calculation of the solvation free energy using the SM8 method. Our
      theoretically predicted barriers are 20.8 and 23.8 kcal mol(-1) for O and N
      attack, respectively, in very good agreement with the experimental values of 20.4
      and 22.3 kcal mol(-1), respectively. Our results support the view that
      hydroxylamine is a very special nucleophile and the reactivity of this functional
      group should be further investigated. 

PMID- 25960005
TI  - High plasma triglyceride levels strongly correlate with low kisspeptin in the
      arcuate nucleus of male rats.
AB  - OBJECTIVE: It is well known that reproductive capacity is lower in obese
      individuals, but what mediators and signals are involved is unclear. Kisspeptin
      is a potent stimulator of GnRH release, and it has been suggested that kisspeptin
      neurons located in the arcuate nucleus transmit metabolic signals to the GnRH
      neurons. METHODS: In this study, we measured body weight and plasma
      concentrations of leptin, insulin, testosterone, and triglycerides after high fat
      diet exposure and correlated these parameters with the number of kisspeptin
      immunoreactive neurons in the arcuate nucleus of male rats. In this model, a high
      fat diet (45% or 60% energy from fat, respectively) or a control diet (10% energy
      from fat) was provided after weaning for three months. RESULTS: We find a
      significant increase in body weight and plasma leptin concentration, but no
      change in the number of kisspeptin-immunoreactive cells with increased fat in the
      diet. Kisspeptin-immunoreactive cells are not correlated with body weight,
      testosterone, leptin or insulin. However, we find that the number of kisspeptin
      immunoreactive cells is strongly and negatively correlated with the level of
      plasma triglycerides (R2=0.49, p=0.004). CONCLUSION: We find a strong negative
      correlation between plasma triglyceride concentrations and the number of
      kisspeptin neurons in the rat arcuate nucleus regardless of the percentage of fat
      in the diet. In line with the lipotoxicity hypothesis, our results suggest that
      it is the level of hypertriglyceridemia per se that is a detrimental factor for
      kisspeptin expression in the arcuate nucleus.

PMID- 25960006
TI  - Impact of repeated asenapine treatment on FosB/DeltaFosB expression in neurons of
      the rat central nucleus of the amygdala: colocalization with corticoliberine
      (CRH) and effect of an unpredictable mild stress preconditioning.
AB  - OBJECTIVES: FosB/DeltaFosB expression in the central amygdalar nucleus (CeA) in
      response to repeated asenapine (ASE) treatment (an atypical antipsychotic used
      for the treatment of schizophrenia) was studied in normal rats and rats
      preconditioned with chronic unpredictable variable mild stress (CMS). The goal of
      this study was to reveal whether repeated ASE treatment for 14 days may: 1)
      induce FosB/DeltaFosB expression in the amygdala, 2) activate CRH-synthesizing
      neurons in the CeA, and 3) interfere with 21 days lasting concomitant CMS
      preconditioning. METHODS: Four groups of animals were studied: controls and ASE-,
      CMS-, and CMS+ASE-treated ones. CMS consisted of the restrain, social isolation,
      crowding, swimming, and cold and lasted 21 days. The ASE and CMS+ASE groups were
      from the 7th day of the experiment treated with ASE (0.3 mg/kg, subcutaneously -
      s.c.) twice a day, i.e. together for 14 days. Controls and CMS groups were
      treated with saline (300 ul/rat, s.c.) twice a day for 14 days. All the animals
      were sacrificed on the 22nd day, i.e. 16-18 hours after the last treatments.
      Single FosB/DeltaFosB, FosB/DeltaFosB colocalizations with CRH, and CRH
      immunolabeled perikarya were investigated in the CeA using a combined light and
      fluorescent immunohistochemistry. RESULTS: The distribution aspect of the black
      FosB/DeltaFosB profiles was homogeneous over the whole CeA and no significant
      differences in the number of FosB/DeltaFosB profiles between the individual
      groups of the rats really occurred. The level of colocalization pattern of
      FosB/DeltaFosB in CRH perikarya was also very similar between the individual
      groups and in each case it reached approximately 10% of double-labeling. No
      differences were also seen in the number of CRH immunolabeled perikarya. The
      density of CRH nerve projections within the CeA was very alike in the individual
      groups of animals investigated. CONCLUSIONS: The study provides a new
      anatomical/functional finding about the lack of the stimulatory effect of the
      repeated ASE treatment on the expression of FosB/DeltaFosB, FosB/DeltaFosB/CRH
      colocalizations, and CRH immunolabeled perikarya number in the CeA. In addition,
      CMS preconditioning itself neither stimulated nor inhibited FosB/DeltaFosB
      expression, nor altered the impact of ASE on the activity of CRH neurons in the
      CeA.

PMID- 25960007
TI  - Influence of thyroid disorders on the kidney expression and plasma activity of
      aminopeptidase A.
AB  - OBJECTIVE: Thyroid disorders may affect blood pressure and renal function
      modifying factors of the plasmatic and kidney renin-angiotensin system such as
      aminopeptidase A (AP A) that metabolizes angiotensin II to angiotensin III. We
      investigated the expression of AP A in the kidney, as well as its enzymatic
      activity in the plasma of euthyroid, hyperthyroid, and hypothyroid adult male
      rats. METHODS: Hyperthyroidism was induced by daily subcutaneous injections of
      tetraiodothyronine. Hypothyroid rats were obtained by administration of
      methimazole in drinking water. Expression of AP A was determined by Western blot
      analysis. Plasma AP A activity was measured fluorometrically using glutamyl-beta
      naphthylamide as substrate. RESULTS: While hyperthyroid rats exhibited lower
      levels of plasma AP A activity than controls, the kidney of hyperthyroid animals
      expressed significantly higher AP A than controls and hypothyroid animals.
      CONCLUSIONS: A discrepancy between the high expression of AP A in kidney of
      hyperthyroid rats and the low activity of AP A measured in plasma and kidney of
      hyperthyroid animals was found. The posttranslational influence of environmental
      biochemical factors may be in part responsible for that divergence.

PMID- 25960008
TI  - Expression of insulin-like growth factor binding protein genes and its hypoxic
      regulation in U87 glioma cells depends on ERN1 mediated signaling pathway of
      endoplasmic reticulum stress.
AB  - OBJECTIVE: The aim of the present study was to examine the association between
      the expression of insulin-like growth binding protein-1 and -2 (IGFBP1 and
      IGFBP2), insulin-like growth factor 2 mRNA binding protein 3/KH domain containing
      protein over-expressed in cancer (IGF2BP3/KOC1), and HtrA serine peptidase
      1/serine protease with IGF-binding domain (HTRA1/PRSS11) genes and function of
      endoplasmic reticulum stress signaling mediated by ERN1 (endoplasmic reticulum to
      nucleus signaling 1) as well as the regulation of these genes by hypoxia in
      U87glioma cells. METHODS: The expression of IGFBP1, IGFBP2, IGF2BP3, and HTRA1
      genes in U87 glioma cells and its subline with ERN1 signaling enzyme loss of
      function, were analyzed by qPCR. Cells underwent to hypoxia exposure (3% oxygen,
      16 h). RESULTS: The blockade of both enzymatic activities (kinase and
      endoribonuclease) of ERN1 in glioma cells led to a significant down-regulation of
      the expression of IGFBP1, IGFBP2, and IGF2BP3 genes and strong up-regulation of
      HTRA1. At the same time, the inhibition of ERN1 endoribonuclease significantly
      increased the expression of IGFBP1, IGFBP2, and HTRA1 genes and did not affect
      the IGF2BP3 gene expression. Hypoxia up-regulated the expression of IGFBP1 and
      IGFBP2 genes in control glioma cells, with more significant changes in IGFBP1
      gene. Furthermore, effect of hypoxia on these gene expressions was significantly
      lower in glioma cells without ERN1 signaling enzyme function. CONCLUSIONS:
      Results of this study demonstrate the dependence of insulin-like growth binding
      proteins as well as IGF2BP3 and HTRA1 gene expressions in U87 glioma cells on
      ERN1 signaling enzyme function and hypoxia, indicating its participation in the
      regulation of metabolic and proliferative processes via IGF/INS receptors,
      because endoplasmic reticulum stress is an important component of tumor growth
      and metabolic diseases.

PMID- 25960009
TI  - Subclinical hypothyroidism in combination with vitamin D deficiency increases the
      risk of impaired left ventricular diastolic function.
AB  - OBJECTIVE: Subclinical hypothyroidism and vitamin D deficiency are common. The
      diastolic function of patients with both subclinical hypothyroidism and vitamin D
      deficiency remains unknown. This study aimed to investigate diastolic dysfunction
      in patients with both subclinical hypothyroidism and vitamin D deficiency.
      SUBJECTS AND METHODS: This study included 254 patients. All patients underwent
      standard Doppler echocardiography. Patients who had risk factors for diastolic
      dysfunction or had used L-thyroxine and vitamin D within the previous 3 months
      were excluded. Vitamin D deficiency was defined as a 25-OH-vitamin D level lower
      than 20 ng/ml, and vitamin D sufficiency was defined as a 25-OH-vitamin D level
      >= 30 ng/ml. Subclinical hypothyroidism was defined as a TSH level of 4.5-10 mU/l
      when the free T4 concentration was normal. RESULTS: The patients were divided
      into 4 groups. Group 1 (n=71) included patients with subclinical hypothyroidism
      and vitamin D deficiency; Group 2 (n=66) included patients with subclinical
      hypothyroidism and vitamin D sufficiency; Group 3 (n=65) included euthyroid
      patients with vitamin D deficiency; and Group 4 (n=52) included euthyroid
      patients with vitamin D sufficiency. LAVI (31.3 +/- 3.2, 28.7 +/- 3.0, 28.4 +/-
      3.4, and 27.9 +/- 3.9; p<0.001) and E/E' values (11.2 +/- 2.7, 8.9 +/- 2.7, 9.1
      +/- 2.9, 8.8 +/- 2.5; p<0.001) were significantly higher in Group 1 than in
      Groups 2, 3 and 4. E' values were significantly lower in Group 1 than in Groups
      2, 3 and 4. CONCLUSION: The coexistence of subclinical hypothyroidism with
      vitamin D deficiency can lead to further deterioration in the LV diastolic
      function via the regulation of intracellular calcium and induction of
      inflammatory activity. Therefore, close follow-up of the diastolic functions of
      these patients could be beneficial.

PMID- 25960010
TI  - Self-awareness of fast eating and its impact on diagnostic components of
      metabolic syndrome among middle-aged Japanese males and females.
AB  - OBJECTIVE: The aim of the present study was to examine the association between
      subjects with self-awareness of fast eating and diagnostic components of
      metabolic syndrome in Japanese middle-aged male and female. PATIENTS AND METHODS:
      Subjects consisted of 3208 males (average age 50.6 years) and 2055 females
      (average age 50.0 years). Associations between subjects with self-awareness of
      fast eating and multiple components of metabolic syndrome (waist circumference,
      body mass index [BMI], blood pressure, and related blood sample tests) were
      evaluated. RESULTS: Significantly more males (57.7%) acknowledged themselves as
      "fast eater" than females (46.5%). Self-reported fast eaters showed significantly
      elevated body weight, BMI, and waist circumference in both genders. However, only
      male self-reported fast eaters showed high levels of blood pressure, fasting
      blood glucose, uric acid, and low-density lipoprotein (LDL)-cholesterol.
      CONCLUSION: Fast eating is associated with diagnostic components of metabolic
      syndrome. The effect of acknowledging themselves as fast eater presents a higher
      impact on males than on females in the middle-aged Japanese population. The
      present study indicates that finding subjects with self-awareness of fast eating
      may lead to the prevention of developing metabolic syndrome.

PMID- 25960011
TI  - Titanium dioxide nanoparticles: some aspects of toxicity/focus on the
      development.
AB  - Nanosized titanium dioxide (TiO2) particles belong to the most widely
      manufactured nanoparticles (NPs) on a global scale because of their
      photocatalytic properties and the related surface effects. TiO2 NPs are in the
      top five NPs used in consumer products. Ultrafine TiO2 is widely used in the
      number of applications, including white pigment in paint, ceramics, food
      additive, food packaging material, sunscreens, cosmetic creams, and, component of
      surgical implants. Data evidencing rapid distribution, slow or ineffective
      elimination, and potential long-time tissue accumulation are especially important
      for the human risk assessment of ultrafine TiO2 and represent new challenges to
      more responsibly investigate potential adverse effects by the action of TiO2 NPs
      considering their ubiquitous exposure in various doses. Transport of ultrafine
      TiO2 particles in systemic circulation and further transition through barriers,
      especially the placental and blood-brain ones, are well documented. Therefore,
      from the developmental point of view, there is a raising concern in the exposure
      to TiO2 NPs during critical windows, in the pregnancy or the lactation period,
      and the fact that human mothers, women and men in fertile age and last but not
      least children may be exposed to high cumulative doses. In this review,
      toxicokinetics and particularly toxicity of TiO2 NPs in relation to the
      developing processes, oriented mainly on the development of the central nervous
      system, are discussed Keywords: nanoparticles, nanotoxicity, nanomaterials,
      titanium dioxide, reproductive toxicity, developmental toxicity, blood brain
      barrier, placental barrier. 

PMID- 25960013
TI  - Silver(I)- or copper(II)-mediated dearomatization of aromatic ynones: direct
      access to spirocyclic scaffolds.
AB  - A high-yielding silver(I)- or copper(II)-catalyzed dearomatizing spirocyclization
      strategy allows the conversion of simple aromatic compounds that contain ynone
      substituents, including indole, anisole, pyrrole, and benzofuran derivatives,
      into functionalized spirocyclic scaffolds. A high-yielding asymmetric variant
      furnishes spirocyclic indolenines in up to 89:11 e.r. 

PMID- 25960012
TI  - Evidence for photochemical production of reactive oxygen species in desert soils.
AB  - The combination of intense solar radiation and soil desiccation creates a short
      circuit in the biogeochemical carbon cycle, where soils release significant
      amounts of CO2 and reactive nitrogen oxides by abiotic oxidation. Here we show
      that desert soils accumulate metal superoxides and peroxides at higher levels
      than non-desert soils. We also show the photogeneration of equimolar superoxide
      and hydroxyl radical in desiccated and aqueous soils, respectively, by a photo
      induced electron transfer mechanism supported by their mineralogical composition.
      Reactivity of desert soils is further supported by the generation of hydroxyl
      radical via aqueous extracts in the dark. Our findings extend to desert soils the
      photogeneration of reactive oxygen species by certain mineral oxides and also
      explain previous studies on desert soil organic oxidant chemistry and
      microbiology. Similar processes driven by ultraviolet radiation may be operating
      in the surface soils on Mars. 

PMID- 25960014
TI  - Water and nonpoint source pollution estimation in the watershed with limited data
      availability based on hydrological simulation and regression model.
AB  - Nonpoint source (NPS) pollution is considered as the main reason for water
      quality deterioration; thus, to quantify the NPS loads reliably is the key to
      implement watershed management practices. In this study, water quality and NPS
      loads from a watershed with limited data availability were studied in a
      mountainous area in China. Instantaneous water discharge was measured through the
      velocity-area method, and samples were taken for water quality analysis in both
      flood and nonflood days in 2010. The streamflow simulated by Hydrological
      Simulation Program-Fortran (HSPF) from 1995 to 2013 and a regression model were
      used to estimate total annual loads of various water quality parameters. The
      concentrations of total phosphorus (TP) and total nitrogen (TN) were much higher
      during the flood seasons, but the concentrations of ammonia nitrogen (NH3-N) and
      nitrate nitrogen (NO3-N) were lower during the flood seasons. Nevertheless, only
      TP concentration was positively correlated with the flow rate. The fluctuation of
      annual load from this watershed was significant. Statistical results indicated
      the significant contribution of pollutant fluxes during flood seasons to annual
      fluxes. The loads of TP, TN, NH3-N, and NO3-N in the flood seasons were accounted
      for 58-85, 60-82, 63-88, 64-81% of the total annual loads, respectively. This
      study presented a new method for estimation of the water and NPS loads in the
      watershed with limited data availability, which simplified data collection to
      watershed model and overcame the scale problem of field experiment method.

PMID- 25960015
TI  - An assessment of polybrominated diphenyl ethers and polychlorinated biphenyls in
      the indoor dust of e-waste recycling facilities in South Africa: implications for
      occupational exposure.
AB  - Workplace exposure to persistent organic pollutants is a concern for human
      health. This study examined the presence of polybrominated diphenyl ethers
      (PBDEs) and polychlorinated biphenyls (PCBs) in the indoor dust from two major e
      waste recycling sites and a university electronic equipment repair workshop in
      Durban, South Africa, in order to evaluate the implication of dust for
      occupational exposure. The mean ?(n = 8)PBDEs and ?(n = 3)PCBs were 20,094 and
      235 ng g(-1), respectively. The levels of PBDEs and PCBs obtained in one of the
      recycling sites (123-27,530 and 161-593 ng g(-1)) were significantly higher than
      the levels obtained (91-7686 and <DL-42 ng g(-1), respectively) in the same site
      after site cleanup/maintenance. Occupational exposure was assessed for different
      exposure scenarios by using the 5th and 95th percentile, and the median and mean
      concentrations measured at the sites. By assuming a mean and a high dust intake
      rate, the average and 95th percentile daily exposure doses (?DED/ng kg(-1) bw
      day(-1)) of PBDEs were 3.98, 8.52 and 7.58, 16.19, respectively, and of PCBs were
      0.047, 0.094 and 0.089, 0.179, respectively. The ?DEDs of PBDEs and PCBs were
      lower than the reference (RfD) values for BDE 47, BDE 99, BDE 153 and BDE 209,
      and Aroclor 1254 and 1016. Nevertheless, continual exposure to high levels of
      these pollutants is a concern; but as shown, the exposure can be significantly
      reduced if the e-waste facilities are cleaned thoroughly regularly. 

PMID- 25960016
TI  - Impact of flash flood events on the distribution of organic pollutants in surface
      sediments from a Mediterranean coastal lagoon (Mar Menor, SE Spain).
AB  - The influence of flash flood events on the input and distribution of polycyclic
      aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and
      organochlorinated pesticides (OCPs) in surface sediments from the Mar Menor
      lagoon were characterized in this study. These contaminants were analyzed in
      surface water samples collected during two flash flood events in the main surface
      watercourse which flow into the Mar Menor lagoon. Surface sediments were sampled
      semiannually before and after flash flood events. The total input of PAHs, OCPs,
      and PCBs (sorbed + dissolved) during two flash flood events was estimated at
      0.98, 1.32, and 0.34 kg, respectively, the main input corresponding to p,p'-DDE
      (1.00 kg). The distribution of organic contaminants in surface sediments was not
      homogeneous as a consequence of the presence of many simultaneous sources and
      different meteorological, hydrodynamic, and physicochemical conditions. As a
      consequence of flash flood events, p,p'-DDE concentrations in surface sediments
      increased significantly in the central and south zones of the lagoon. However, in
      the case of PCBs, a dilution effect was observed in the south zone after such
      events, reducing the environmental risk. These changes in the pollutant
      distribution persisted at least 1 year later (autumn 2010), showing that the
      impact of flood events in the distribution of persistent organic contaminants in
      Mediterranean coastal lagoons is of relevance according to the ecological risk
      assessment carried out. The impact of these events should be also considered in
      other coastal systems, especially in semiarid and semiconfined areas.

PMID- 25960017
TI  - Stable sulfur isotope ratios and water-soluble inorganic compositions of PM10 in
      Yichang City, central China.
AB  - Chemical and sulfate-sulfur isotopic compositions of water-soluble inorganic ions
      were analyzed for aerosol sample particulate matter with aerodynamic diameter
      <=10 MUm (PM10) collected during 17-28 December 2012 at Yichang City, Hubei
      Province, central China. Most water-soluble inorganic ions, except for NO3 (-)
      and NH4 (+), showed slightly higher concentration in daytime than in nighttime,
      and the major detected ions followed the order of SO4 (2-) > NO3 (-) > Ca(2+) >
      Na(+) > NH4 (+) > Cl(-) in daytime and nighttime, of which SO4 (2-) is the most
      abundant ionic component that accounted for about 49.1 and 49.3 % of the total
      mass of analyzed ions in daytime and nighttime, respectively. According to the
      correlation coefficients among the mass concentrations of water-soluble inorganic
      ions, there may mainly exist in forms of (NH4)2SO4 and NH4NO3 in daytime and
      NH4NO3 in nighttime. The delta(34)S values of sulfate ranged from +2.82 to +4.63
      0/00 (average +3.97 0/00) in daytime and from +2.90 to +5.39 0/00 (average +4.08
      0/00) in nighttime, indicating that the source of sulfate in PM10 was mainly
      derived from coal burning (delta(34)S, +3.68 0/00) in Yichang City. The [NO3 (
      )]/[SO4 (2-)] mass ratio varied between 0.2 and 0.6 with an average of 0.4 in
      daytime and 0.1 to 0.8 with an average of 0.4 in nighttime, which implying that
      the stationary source emissions would be more important than the vehicle
      emissions in the studied area. As a whole, the mixture of coal burning, vehicle
      exhaust, and resuspended road dust would be responsible for the sources of PM10
      in Yichang City during wintertime. 

PMID- 25960018
TI  - Residence time analysis of photochemical buildup of ozone in central eastern
      China from surface observation at Mt. Tai, Mt. Hua, and Mt. Huang in 2004.
AB  - Using data from surface observation, backward trajectories, and residence time
      analysis, the amounts of regional photochemical ozone buildup due to the large
      scale anthropogenic sources in central eastern China (CEC, 30.5-40.5 N, 112.5
      122.5 E) at Mt. Tai, Mt. Hua, and Mt. Huang in 2004 were quantified. It was found
      that the CEC anthropogenic sources influenced the air masses and the associated
      ozone production most at Mt. Tai, located at the center of CEC domain. At Mt. Hua
      to the west of CEC domain and at Mt. Huang to the south of CEC domain, the air
      masses and the associated ozone production showed less CEC anthropogenic
      influences on a regional scale. At Mt. Tai and Mt. Huang, the ozone mixing ratios
      in the air masses that passed over polluted source regions in CEC increased
      during the first 40-70 h after arrival and showed the highest production rate of
      31.2 and 12.2 ppb/day, respectively, in May and June. It was estimated that the
      CEC anthropogenic sources contributed 34-42% of ozone at Mt. Tai and 8-14% at Mt.
      Huang during this ozone peak season. The large contributions from CEC sources
      during fall season (Sep-Nov) were also estimated as 31-44 and 17-23% but with the
      lower ozone production rate of 22.6 and 8.4 ppb/day, respectively, for Mt. Tai
      and Mt. Huang.

PMID- 25960019
TI  - Prevention of Dabigatran-Related Gastrointestinal Bleeding With Gastroprotective
      Agents: A Population-Based Study.
AB  - BACKGROUND & AIMS: Use of dabigatran, an inhibitor of thrombin, increases the
      risk of gastrointestinal bleeding (GIB). However, it is not clear whether
      gastroprotective agents (GPAs) prevent GIB in dabigatran users. We investigated
      the risk of GIB and the role of gastroprotective agents (including proton pump
      inhibitors and histamine type-2-receptor antagonists) in patients using
      dabigatran. METHODS: We performed a retrospective cohort study using a population
      wide database managed by the Hong Kong Hospital Authority. Patients newly
      prescribed dabigatran from 2010 through 2013 were included in the analysis.
      Poisson regression was used to assess the risk of GIB in dabigatran users by
      incidence rate ratio (IRR), adjusted for patient characteristics, comorbidities,
      and concurrent medications. RESULTS: Among the 5041 patients newly prescribed
      dabigatran, 124 (2.5%) developed GIB during follow-up evaluation (4.2/100 patient
      years). The risk of GIB in this population increased among patients 75 years and
      older (IRR, 2.47; 95% confidence interval [CI], 1.66-3.68), patients with a
      history of peptic ulcers or GIB (IRR, 2.31; 95% CI, 1.54-3.46), and patients who
      used aspirin (IRR, 1.52; 95% CI, 1.03-2.24). Concomitant use of gastroprotective
      agents was associated with a reduced risk of GIB (IRR, 0.52; 95% CI, 0.35-0.77).
      Subcategory analysis showed that use of proton pump inhibitors (IRR, 0.53; 95%
      CI, 0.31-0.91) or histamine type-2-receptor antagonists (IRR, 0.61; 95% CI, 0.40
      0.94) were associated with a lower risk of GIB. Further analysis showed that the
      risk reduction by gastroprotective agents was significant for only upper GIB
      (IRR, 0.29; 95% CI, 0.15-0.54), and only for patients with a prior history of
      peptic ulcers or GIB (IRR, 0.14; 95% CI, 0.06-0.30). CONCLUSIONS: In the Hong
      Kong population, use of gastroprotective agents was associated with a reduced
      risk of GIB in patients taking dabigatran. The association was stronger for upper
      GIB than lower GIB, and in patients with a prior history of peptic ulcers or GIB.

PMID- 25960021
TI  - A molecular tuning fork in single-molecule mechanochemical sensing.
AB  - The separate arrangement of target recognition and signal transduction in
      conventional biosensors often compromises the real-time response and can
      introduce additional noise. To address these issues, we combined analyte
      recognition and signal reporting by mechanochemical coupling in a single-molecule
      DNA template. We incorporated a DNA hairpin as a mechanophore in the template,
      which, under a specific force, undergoes stochastic transitions between folded
      and unfolded hairpin structures (mechanoescence). Reminiscent of a tuning fork
      that vibrates at a fixed frequency, the device was classified as a molecular
      tuning fork (MTF). By monitoring the lifetime of the folded and unfolded hairpins
      with equal populations, we were able to differentiate between the mono- and
      bivalent binding modes during individual antibody-antigen binding events. We
      anticipate these mechanospectroscopic concepts and methods will be instrumental
      for the development of novel bioanalyses. 

PMID- 25960020
TI  - Heparin enhances uptake of platelet factor 4/heparin complexes by monocytes and
      macrophages.
AB  - BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an iatrogenic complication
      of heparin therapy caused by antibodies to a self-antigen, platelet factor (4)
      and heparin. The reasons why antibodies form to PF4/heparin, but not to PF4 bound
      to other cellular glycosaminoglycans are poorly understood. OBJECTIVE: To
      investigate differences in cellular responses to cell-bound PF4 and PF4/heparin
      complexes, we studied the internalization of each by peripheral blood-derived
      monocytes, dendritic cells and neutrophils. METHODS AND RESULTS: Using unlabeled
      and fluorescently-labeled antigen and/or labeled monoclonal antibody to
      PF4/heparin complexes (KKO), we show that PF4/heparin complexes are taken up by
      monocytes in a heparin-dependent manner and are internalized by human monocytes
      and dendritic cells, but not by neutrophils. Complexes of PF4/low-molecular
      weight heparin and complexes composed of heparin and murine PF4, protamine or
      lysozyme are internalized similarly, suggesting a common endocytic pathway.
      Uptake of complexes is mediated by macropinocytosis, as shown by inhibition using
      cytochalasin D and amiloride. Internalized complexes are transported intact to
      late endosomes, as indicated by co-staining of vesicles with KKO and lysosomal
      associated membrane protein-2 (LAMP-2). Lastly, we show that cellular uptake is
      accompanied by expression of MHCII and CD83 co-stimulatory molecules.
      CONCLUSIONS: Taken together, these studies establish a distinct role for heparin
      in enhancing antigen uptake and activation of the initial steps in the cellular
      immune response to PF4-containing complexes.

PMID- 25960022
TI  - Keratocystoma of the parotid gland: a case report and review of previous
      publications.
AB  - Keratocystoma is a rare benign tumour of the salivary glands. We report a patient
      who presented with a mass in the left parotid gland that was treated by subtotal
      parotidectomy and he was free of recurrence seven years later. After histological
      and immunohistochemical examinations we identified a keratocystoma. 

PMID- 25960023
TI  - Spontaneous regeneration of bone after removal of a vascularised fibular bone
      graft from a mandibular segmental defect: a case report.
AB  - Spontaneous bony regeneration of a segmental mandibular defect is rarely, if
      ever, reported and its mechanism is not clearly understood. However, several
      predisposing factors, including the presence of the periosteum, the age of the
      patient, the presence of local infection or stumps or fragments of bone,
      postoperative immobilisation, and functional or mechanical stress on the
      mandibular stumps, have all been suggested. We present a rare case of unexpected
      spontaneous regeneration of bone after removal of a vascularised fibular bone
      graft with osteomyelitis in a 48-year-old patient. In particular, the periosteum
      of the bone graft rather than the mandibular site was preserved. We know of no
      such previous report. 

PMID- 25960024
TI  - A randomised clinical trial comparing the patient comfort and efficacy of three
      different graduated compression stockings in the prevention of postoperative deep
      vein thrombosis.
AB  - AIMS AND OBJECTIVES: To compare the comfort levels of patients regarding the use
      of three different graduated compression stockings and to analyse the efficacies
      of the graduated compression stockings in relation to patient comfort and
      compliance in prevention of postoperative deep vein thrombosis. BACKGROUND:
      Graduated compression stockings are very important with other prophylaxis methods
      in postoperative deep vein thrombosis prophylaxis. In meta-analyses and
      systematic review studies, it was reported that knee-length and thigh-length
      graduated compression stockings had similar efficacies. However, there is no
      randomised study in literature regarding the patient problems and levels of
      comfort with the use of graduated compression stockings of different sizes and
      pressures. DESIGN: A randomised clinical trial design. METHODS: A total of 219
      patients were randomised into three groups (n = 73 in each group). Group I was
      given low-pressure, knee-length graduated compression stockings, group II was
      given low-pressure, thigh-length graduated compression stockings and group III
      was given moderate-pressure, knee-length graduated compression stockings. The
      level of patients comfort regarding the graduated compression stockings and
      occurrence of deep vein thrombosis were examined. RESULTS: The vast majority of
      the patients (79.5%) in group III and 52.1% of the patients in group II stated
      experiencing problems during the use of the graduated compression stockings (p <
      0.001). The graduated compression stockings were reported by the patients as
      being very comfortable in the group I (p < 0.001). No findings of thrombosis were
      observed in any of the groups. CONCLUSION: The low-pressure, knee-length
      graduated compression stockings are as effective as the other graduated
      compression stockings of different pressures and sizes in the postoperative deep
      vein thrombosis prophylaxis, and the patients have fewer problems while using
      these graduated compression stockings with a high satisfaction. RELEVANCE TO
      CLINICAL PRACTICE: The combined use of pharmacological, mechanical and physical
      methods and patient education is effective in the prevention of postoperative
      deep vein thrombosis. The use of low-pressure, knee-length graduated compression
      stockings in clinical practice may be recommended, as the patients have fewer
      problems while using these graduated compression stockings with a high
      satisfaction.

PMID- 25960026
TI  - Call for submissions.

PMID- 25960025
TI  - Changes in Markers of Ovarian Reserve After Laparoscopic Ovarian Cystectomy.
AB  - STUDY OBJECTIVE: This study was conducted to determine the changes in ovarian
      reserve markers after laparoscopic ovarian cystectomy (LOC). DESIGN: Prospective
      cohort study (Canadian Task Force classification II-2). SETTING: University
      teaching hospital. PATIENTS: Fifty 50 patients who underwent LOC were
      prospectively examined to determine the changes in serum markers of ovarian
      reserve, starting from 1 month before and 3 months after consecutive operations.
      INTERVENTIONS: Changes in serum markers were compared between the following
      groups: endometrioma cysts (n = 26) versus nonendometrioma cysts (n = 24),
      unilateral cystectomy (n = 38) versus bilateral cystectomy (n = 12), and
      bilateral endometrioma extirpation (n = 10) versus other cystectomy operations (n
      = 40). MEASUREMENTS AND MAIN RESULTS: A significant change was noticed between
      the preoperative and postoperative antimullerian hormone (AMH) levels (2.67 +/-
      2.67 ng/mL vs 1.84 +/- 1.72 ng/mL, p < .0001). Serum AMH levels were found to be
      significantly decreased in endometrioma (p = .002), nonendometrioma (p = .019),
      unilateral cystectomy (p = .001), bilateral cystectomy (p = .005), bilateral
      endometrioma (p = .011), and cysts other than bilateral endometrioma (p = .000)
      groups. CONCLUSION: The ovarian reserve was found to be diminished after LOC
      regardless of the presence of endometrioma that could be distinguishable by serum
      AMH levels.

PMID- 25960027
TI  - On the handedness of helical aggregates of C3 tricarboxamides: a multichiroptical
      characterization.
AB  - A complete chiroptical characterization of the supramolecular polymers formed by
      tricarboxamides and is performed using ECD, VCD and CPL dichroic techniques. The
      helical aggregates show an intense CPL signal and their absolute P- or M
      configuration is assigned with the help of theoretical calculations. 

PMID- 25960028
TI  - Outcomes, costs and cost-effectiveness of treating hepatitis C with direct acting
      antivirals.
AB  - Hepatitis C is a global public health burden. Long-term consequences are the
      development of liver cirrhosis and hepatocellular carcinoma. Introduction of
      different direct acting antivirals targeting the hepatitis C proteins has
      considerably increased rates of sustained viral response. First active substances
      introduced in 2011 were NS3/4A protease inhibitors telaprevir and boceprevir. In
      2013/2014 the second generation of direct acting antivirals sofosbuvir,
      simeprevir, daclatasvir, ledipasvir and 3D therapy containing
      ombitasvir/paritaprevir/ritonavir and dasabuvir followed. This review focuses on
      treatment outcomes and costs of introduced direct acting antivirals. We provide
      an overview on SVR-rates in clinical trials and clinical practice, treatment
      costs in different countries as well as results of cost-effectiveness analyses
      for different treatment strategies.

PMID- 25960030
TI  - Photoresponsive Amphiphilic Macrocycles Containing Main-Chain Azobenzene
      Polymers.
AB  - Herein, the first example of photosensitive cyclic amphiphilic homopolymers
      consisting of multiple biphenyl azobenzene chromophores in the cyclic main chain
      tethered with hydrophilic tetraethylene glycol monomethyl ether units is
      presented. The synthetic approach involves sequentially performed thermal
      catalyzed "click" step-growth polymerization in bulk, and Cu(I)-catalyzed azide
      alkyne cycloaddition (CuAAC) intramolecular cyclization from alpha-alkyne/omega
      azide linear precursors. It is observed that such amphiphilic macrocycles exhibit
      increased glass transition temperatures (Tg ), slightly faster trans-cis-trans
      photoisomerization, and enhanced fluorescence emission intensity compared with
      the corresponding linear polymers. In addition, the cyclic amphiphilic
      homopolymers self-assemble into spherical nanoparticles with smaller sizes which
      possess slower photoresponsive behaviors in a tetrahydrofuran/water mixture
      compared with those of the linear ones. All these interesting observations
      suggest that the cyclic topology has a great influence on the physical properties
      and self-assembly behavior of these photoresponsive amphiphilic macrocycles in
      general. 

PMID- 25960031
TI  - Role of TachoSil(r) in distal pancreatectomy: a single center experience.
AB  - AIM: Distal pancreatectomies (DP) are associated with high risk of postoperative
      complications, and in many series higher morbidity rate than
      duodenopancreatectomies has been reported. To evaluate the role of a collagen
      sponge with human fibrinogen and thrombin film (TachoSil(r)) in limiting the
      incidence of complications after DP. METHODS: From 1996 to 2013, 221 patients
      have been submitted to distal pancreatectomy (+/- splenectomy) in our Division. A
      retrospective analysis has been conducted in a group of 36 consecutive and
      prospectively collected DP treated with intraoperative placement of TachoSil(r)
      on pancreatic stump from 2010 to 2013 (group 1). A control series of 36
      consecutive patients (group 2) was matched 1:1 from hystorical database. The
      variables considered in the analysis were: age, gender, ASA score, pancreatic
      texture (hard vs. soft), histology, operative time, postoperative mortality,
      morbility (postoperative pancreatic fistula - POPF, postoperative hemorrage -
      PPH, delayed gastric emptying - DGE) and hospital stay. Differences between POPF,
      PPH, DGE and hospital stays between grops were investigated with chi2 and t
      Student test. Univariate analysis was conducted to determine factors related to
      POPF development. Statistical analysis was performed using freeware Microsoft
      Excel based program. RESULTS: Post operative mortality was 0% in both groups.
      POPF were registered in 36.1% (13/36) and 41.6 % (15/36) in groups 1 and 2,
      respectively (P=n.s.); in group 1 we didn't observe grade C POPF, while 4
      patients in control group developed grade C POPF (P<0,05). No differences were
      found between two groups in terms of incidence of PPH and DGE. The median
      duration of postoperative hospital stay in group 1 was 21.8 (7-189) days compared
      with 31.13 (9-249) days in group 2 (P<0.001). CONCLUSION: The use of TachoSil(r)
      seems to be associated with lower incidence of grade C POPF but larger controlled
      trials are needed to surely assess the usefulness of TachoSil(r) in pancreatic
      surgery in order to reduce pancreatic specific complications and their severity.

PMID- 25960032
TI  - Genetic variants of the unsaturated fatty acid receptor GPR120 relating to
      obesity in dogs.
AB  - G protein-coupled receptor (GPR) 120 is an unsaturated fatty acid receptor, which
      is associated with various physiological functions. It is reported that the
      genetic variant of GPR120, p.Arg270His, is detected more in obese people, and
      this genetic variation functionally relates to obesity in humans. Obesity is a
      common nutritional disorder also in dogs, but the genetic factors have not ever
      been identified in dogs. In this study, we investigated the molecular structure
      of canine GPR120 and searched for candidate genetic variants which may relate to
      obesity in dogs. Canine GPR120 was highly homologous to those of other species,
      and seven transmembrane domains and two N-glycosylation sites were conserved.
      GPR120 mRNA was expressed in lung, jejunum, ileum, colon, hypothalamus,
      hippocampus, spinal cord, bone marrow, dermis and white adipose tissues in dogs,
      as those in mice and humans. Genetic variants of GPR120 were explored in client
      owned 141 dogs, resulting in that 5 synonymous and 4 non-synonymous variants were
      found. The variant c.595C>A (p.Pro199Thr) was found in 40 dogs, and the gene
      frequency was significantly higher in dogs with higher body condition scores,
      i.e. 0.320 in BCS4-5 dogs, 0.175 in BCS3 dogs and 0.000 in BCS2 dogs. We conclude
      that c.595C>A (p.Pro199Thr) is a candidate variant relating to obesity, which may
      be helpful for nutritional management of dogs. 

PMID- 25960033
TI  - The combined effect of clothianidin and environmental stress on the behavioral
      and reproductive function in male mice.
AB  - Neonicotinoids, some of the most widely used pesticides in the world, act as
      agonists to the nicotinic acetylcholine receptors (nAChRs) of insects, resulting
      in death from abnormal excitability. Neonicotinoids unexpectedly became a major
      topic as a compelling cause of honeybee colony collapse disorder, which is
      damaging crop production that requires pollination worldwide. Mammal nAChRs
      appear to have a certain affinity for neonicotinoids with lower levels than those
      of insects; there is thus rising concern about unpredictable adverse effects of
      neonicotinoids on vertebrates. We hypothesized that the effects of neonicotinoids
      would be enhanced under a chronic stressed condition, which is known to alter the
      expression of targets of neonicotinoids, i.e., neuronal nAChRs. We performed
      immunohistochemical and behavioral analyses in male mice actively administered a
      neonicotinoid, clothianidin (CTD; 0, 10, 50 and 250 mg/kg/day), for 4 weeks under
      an unpredictable chronic stress procedure. Vacuolated seminiferous epithelia and
      a decrease in the immunoreactivity of the antioxidant enzyme glutathione
      peroxidase 4 were observed in the testes of the CTD+stress mice. In an open field
      test, although the locomotor activities were not affected, the anxiety-like
      behaviors of the mice were elevated by both CTD and stress. The present study
      demonstrates that the behavioral and reproductive effects of CTD become more
      serious in combination with environmental stress, which may reflect our actual
      situation of multiple exposure. 

PMID- 25960035
TI  - A novel electroencephalography-based tool for objective assessment of network
      dynamics activated by nociceptive stimuli.
AB  - BACKGROUND: Pain perception is typically assessed using subjective measures; an
      objective measure of the response to pain would be valuable. In this study, Brain
      Network Activation (BNA), a novel multivariate pattern analysis and scoring
      algorithm, was applied to event-related potentials (ERPs) elicited by cortical
      responses to brief heat stimuli. Objectives of this study were to evaluate the
      utility of BNA as a quantitative and qualitative measure of cortical response to
      pain. METHODS: Contact Heat Evoked Potentials (CHEPs) data were collected from 17
      healthy, right-handed volunteers (10 M, 7F) using 5 different temperatures (35,
      41, 46, 49 and 52  degrees C). A set of spatio-temporal activity patterns common
      to all the subjects in the group (Reference Brain Network Model; RBNM) was
      generated using the BNA algorithm, based on evoked responses at 52  degrees C.
      RESULTS: Frame by frame 'unfolding' of the brain network across time showed
      qualitative differences between responses to painful and non-painful stimuli.
      Brain network activation scores were shown to be a better indicator of the
      individual's sensitivity to pain when compared to subjective pain ratings.
      Additionally, BNA scores correlated significantly with temperature, demonstrated
      good test-retest reliability, as well as a high degree of sensitivity,
      specificity and accuracy in correctly categorizing subjects who reported stimuli
      as painful. CONCLUSIONS: These results may provide evidence that the multivariate
      analysis performed with BNA may be useful as a quantitative, temporally sensitive
      tool for assessment of pain perception.

PMID- 25960034
TI  - Product Control in Alkene Trifluoromethylation: Hydrotrifluoromethylation,
      Vinylic Trifluoromethylation, and Iodotrifluoromethylation using Togni Reagent.
AB  - Hydrotrifluoromethylation, vinylic trifluoromethylation, and
      iodotrifluoromethylation of simple alkenes have been achieved by using Togni
      reagent in the absence of any transition metal catalyst. These reactions were
      readily controllable by selection of appropriate salts and solvents. The addition
      of K2CO3 afforded the hydrotrifluoromethylation product, with DMF acting not only
      as a solvent, but also as the hydrogen source. In contrast, the use of tetra-n
      butylammonium iodide (TBAI) in 1,4-dioxane resulted in vinylic
      trifluoromethylation, while the use of KI afforded the iodotrifluoromethylation
      product. The vinylic trifluoromethylation product was obtained by treatment of
      the iodotrifluoromethylation product with ammonium 2-iodobenzoate, indicating
      that it was formed through an elimination reaction of the in-situ-generated
      iodotrifluoromethylation product, and the solubility of the resulting 2
      iodobenzoate salt plays a key role in the product switching. A radical-clock
      experiment showed that these reactions proceed via radical intermediates.

PMID- 25960036
TI  - Long-term consequences of perinatal and adolescent cannabinoid exposure on neural
      and psychological processes.
AB  - Marihuana is the most widely consumed illicit drug, even among adolescents and
      pregnant women. Given the critical developmental processes that occur in the
      adolescent and fetal nervous system, marihuana consumption during these stages
      may have permanent consequences on several brain functions in later adult life.
      Here, we review what is currently known about the long-term consequences of
      perinatal and adolescent cannabinoid exposure. The most consistent findings point
      to long-term impairments in cognitive function that are associated with
      structural alterations and disturbed synaptic plasticity. In addition, several
      neurochemical modifications are also evident after prenatal or adolescent
      cannabinoid exposure, especially in the endocannabinoid, glutamatergic,
      dopaminergic and opioidergic systems. Important sexual dimorphisms are also
      evident in terms of the long-lasting effects of cannabinoid consumption during
      pregnancy and adolescence, and cannabinoids possibly have a protective effect in
      adolescents who have suffered traumatic life challenges, such as maternal
      separation or intense stress. Finally, we suggest some future research directions
      that may encourage further advances in this exciting field. 

PMID- 25960037
TI  - A case of cherubism with spondyloarthropathy.

PMID- 25960039
TI  - Common Anomalous Muscles Encountered During Upper Extremity Surgery.

PMID- 25960038
TI  - Assessing suicidal ideation in individuals at clinical high risk for psychosis.
AB  - BACKGROUND: The majority of individuals with schizophrenia and other psychotic
      illnesses have had suicidal ideation at some point during the illness. However,
      little is known about the variation in level and intensity of suicidal ideation
      and symptoms in the attenuated stage of psychotic illness. Our aims were to
      assess prevalence of suicidal ideation in this at risk group, and to examine the
      severity and intensity of suicidal ideation, and their relation to symptoms.
      METHODS: Suicidal ideation was assessed in 42 clinical high-risk participants
      using the Columbia Suicide Severity Rating Scale (C-SSRS). We hypothesized that
      prevalence rates would be similar to what was found in previous studies, and
      individuals with suicidal ideation would have higher positive and negative
      symptoms, with poorer functioning. We assessed levels of severity and intensity
      of suicidal ideation related to these symptoms, and examined how depressive
      symptoms affected these relationships. RESULTS: Nearly half (42.9%) of
      participants reported having current suicidal ideation. We found no relationship
      to positive symptoms. However, severity and intensity of suicidal ideation were
      found to be related to negative symptoms and level of functioning. When
      controlling for depressive symptoms during exploratory analysis, this
      relationship still emerged. CONCLUSIONS: This study adds to the literature
      demonstrating the complex nature of suicidal ideation in psychotic illness. The C
      SSRS has shown to be helpful in determining relationships between severity and
      intensity in suicidal ideation in relation to specific symptoms in a research
      setting.

PMID- 25960040
TI  - Size Fractionation of Graphene Oxide Sheets via Filtration through Track-Etched
      Membranes.
AB  - Graphene oxide (GO) fractionation is achieved by size-exclusive passing of GO
      sheets through size-defined pores of track-etched membranes, which separate the
      GO sample into three portions with narrow size distributions. The method reported
      can be used for the performance improvement of graphene-based materials. 

PMID- 25960041
TI  - Hitting cancers' weak spots: vulnerabilities imposed by p53 mutation.
AB  - The tumor suppressor protein p53 plays a critical role in limiting malignant
      development and progression. Almost all cancers show loss of p53 function,
      through either mutation in the p53 gene itself or defects in the mechanisms that
      activate p53. While reactivation of p53 can effectively limit tumor growth, this
      is a difficult therapeutic goal to achieve in the many cancers that do not retain
      wild type p53. An alternative approach focuses on identifying vulnerabilities
      imposed on cancers by virtue of the loss of or alterations in p53, to identify
      additional pathways that can be targeted to specifically kill or inhibit the
      growth of p53 mutated cells. These indirect ways of exploiting mutations in p53 -
      which occur in more than half of all human cancers - provide numerous exciting
      therapeutic possibilities. 

PMID- 25960042
TI  - Electrically evoked multiplet discharges are associated with more marked clinical
      deterioration in motor neuron disease.
AB  - INTRODUCTION: The aim of this study was to determine whether electrically evoked
      multiplet discharges (MDs) are related to severity of clinical deterioration in
      motor neuron disease (MND). METHODS: Stimulated high-density surface
      electromyographic (HDsEMG) recordings were performed in thenar muscles. Data were
      collected from 31 MND patients. MDs from the HDsEMG recordings were determined at
      baseline. ALSFRS-R scores were obtained at baseline and at a maximum of 16 weeks
      follow-up. RESULTS: The presence of MDs was associated with progressive
      deterioration of ALSFRS-R score (P = 0.02) and fine motor function (FMF) (P <
      0.001). Patients who had a higher number of motor units that generated MDs (r =
      0.61, P < 0.001) and patients who had a higher number of MDs (as percentage of
      applied stimuli) (r = 0.59, P = 0.001) had a more severe decline in FMF.
      CONCLUSIONS: Electrically evoked MDs are associated with more marked clinical
      deterioration in patients with MND.

PMID- 25960043
TI  - Multilayer thin films with compositional PbZr0.52Ti0.48O3/Bi1.5Zn1.0Nb1.5O7
      layers for tunable applications.
AB  - The dielectric properties and tunability of multilayer thin films with
      compositional PbZr0.52Ti0.48O3/Bi1.5Zn1.0Nb1.5O7 (PZT/BZN) layers (PPBLs)
      fabricated by pulsed laser deposition on Pt/TiO2/SiO2/Si substrate have been
      investigated. Dielectric measurements indicate that the PZT/BZN bilayer thin
      films exhibit medium dielectric constant of about 490, low loss tangent of 0.017,
      and superior tunable dielectric properties (tunability=49.7% at 500 kV/cm) at a
      PZT/BZN thickness ratio of 3, while the largest figure of merit is obtained as
      51.8. The thickness effect is discussed with a series connection model of bilayer
      capacitors, and the calculated dielectric constant and loss tangent are obtained.
      Furthermore, five kinds of thin-film samples comprising single bilayers, two,
      three, four and five PPBLs were also elaborated with the final same thickness.
      The four PPBLs show the largest dielectric constant of ~538 and tunability of
      53.3% at a maximum applied bias field of 500 kV/cm and the lowest loss tangent of
      ~0.015, while the largest figure of merit is 65.6. The results indicate that four
      PPBLs are excellent candidates for applications of tunable devices.

PMID- 25960044
TI  - Enteric glial cells are associated with stress-induced colonic hyper-contraction
      in maternally separated rats.
AB  - BACKGROUND: Enteric glial cells (EGCs) play important roles in enteric integrity
      and regulation of gastrointestinal function. However, whether EGCs undergo
      pathophysiological changes in stress-associated gastrointestinal disorders is
      unknown. We investigated structural and functional alterations in colonic EGCs
      and their roles in colonic contraction in an irritable bowel syndrome (IBS)
      model. METHODS: As a chronic stress, male Wistar rats underwent 3-h maternal
      separation during postnatal days 2-14. As an acute stress, we used water
      immersion stress (4 h) in adulthood (at 8 weeks). We quantitatively and
      morphologically evaluated enteric neurons and EGCs using whole-mount longitudinal
      muscle-myenteric plexus preparations. Colonic contraction was analyzed with
      electrical field stimulation (EFS). KEY RESULTS: Glial fibrillary acidic protein
      (GFAP) expression and the number of total, cholinergic, and nitrergic neurons
      were unchanged in maternally separated rats with acute stress (combined stress:
      an IBS model) compared with controls. However, the density of GFAP-positive EGC
      processes that apparently overlapped with the neurons and the extent of bulbous
      swelling of terminals increased according to the stress intensity: control, acute
      stress, maternal separation, and combined stress. EFS-induced colonic
      contractions were significantly greater in the combined stress rats than in
      controls. Higher dose of fluorocitrate, a selective inhibitor of EGC metabolism,
      was required to inhibit both EFS-induced contraction and EGCs activation in the
      combined stress rats than in controls. CONCLUSIONS & INFERENCES: Colonic EGCs
      exhibited structural alterations according to the stress intensity. EGCs were
      associated with stress-induced colonic hyper-contraction in the combined stress
      rats, which may underlie the pathogenesis of IBS.

PMID- 25960045
TI  - A novel stem cell associated marker identified by monoclonal antibody HESC5:3
      differentiates between neoplastic lesions in follicular thyroid neoplasms.
AB  - Follicular thyroid lesions are the bane of cytopathology. Differentiation between
      adenoma and carcinoma is impossible, and often these neoplasms are
      indistinguishable even from uninodular goitre. In other cancers as well, a theory
      of stem cells as the origin of cancer has been discussed in thyroid
      carcinogenesis. We aimed to examine a novel stem cell associated marker
      identified by monoclonal antibody HESC5:3 in follicular lesions in an attempt to
      find a marker for differential diagnosis in thyroid cytopathology. HESC5:3 was
      raised against and is specific for undifferentiated human embryonic stem cells.
      The epitope of this novel antibody is to be defined. Immunohistochemical
      expression of HESC5:3 was examined in clinical material comprised of follicular
      neoplasms (83 adenomas, 43 carcinomas) and non-neoplastic lesions (41 goitrous,
      22 hyperplastic, 23 normal tissue specimens). Staining differed significantly
      between neoplastic and non-neoplastic lesions. Nuclear staining was increased in
      non-neoplastic cells, whereas in neoplastic cells expression was mainly
      cytoplasmic. There was no difference between benign and malignant lesions,
      suggesting a role in early tumourigenesis. In conclusion, the HESC5:3 epitope may
      be of benefit as a neoplasia marker in distinguishing between uninodular goitre
      and neoplasia. Characterization of the epitope would increase the interest in
      this promising new stem cell associated marker. 

PMID- 25960046
TI  - UCP2 inhibition sensitizes breast cancer cells to therapeutic agents by
      increasing oxidative stress.
AB  - Modulation of oxidative stress in cancer cells plays an important role in the
      study of the resistance to anticancer therapies. Uncoupling protein 2 (UCP2) may
      play a dual role in cancer, acting as a protective mechanism in normal cells,
      while its overexpression in cancer cells could confer resistance to chemotherapy
      and a higher survival through downregulation of ROS production. Thus, our aim was
      to check whether the inhibition of UCP2 expression and function increases
      oxidative stress and could render breast cancer cells more sensitive to cisplatin
      (CDDP) or tamoxifen (TAM). For this purpose, we studied clonogenicity,
      mitochondrial membrane potential (DeltaPsim), cell viability, ROS production,
      apoptosis, and autophagy in MCF-7 and T47D (only the last four determinations)
      breast cancer cells treated with CDDP or TAM, in combination or without a UCP2
      knockdown (siRNA or genipin). Furthermore, survival curves were performed in
      order to check the impact of UCP2 expression in breast cancer patients. UCP2
      inhibition and cytotoxic treatments produced a decrease in cell viability and
      clonogenicity, in addition to an increase in DeltaPsim, ROS production,
      apoptosis, and autophagy. It is important to note that CDDP decreased UCP2
      protein levels, so that the greatest effects produced by the UCP2 inhibition in
      combination with a cytotoxic treatment, with regard to treatment alone, were
      observed in TAM+UCP2siRNA-treated cells. Moreover, this UCP2 inhibition caused
      autophagic cell death, since apoptosis parameters barely increased after UCP2
      knockdown. Finally, survival curves revealed that higher UCP2 expression
      corresponded with a poorer prognosis. In conclusion, UCP2 could be a therapeutic
      target in breast cancer, especially in those patients treated with tamoxifen. 

PMID- 25960047
TI  - Exploring the possible link between MeCP2 and oxidative stress in Rett syndrome.
AB  - Rett syndrome (RTT, MIM 312750) is a rare and orphan progressive
      neurodevelopmental disorder affecting girls almost exclusively, with a frequency
      of 1/15,000 live births of girls. The disease is characterized by a period of 6
      to 18 months of apparently normal neurodevelopment, followed by early
      neurological regression, with a progressive loss of acquired cognitive, social,
      and motor skills. RTT is known to be caused in 95% of the cases by sporadic de
      novo loss-of-function mutations in the X-linked methyl-CpG-binding protein 2
      (MECP2) gene encoding methyl-CpG binding protein 2 (MeCP2), a nuclear protein
      able to regulate gene expression. Despite almost two decades of research into the
      functions and role of MeCP2, little is known about the mechanisms leading from
      MECP2 mutation to the disease. Oxidative stress (OS) is involved in the
      pathogenic mechanisms of several neurodevelopmental and neurodegenerative
      disorders, although in many cases it is not clear whether OS is a cause or a
      consequence of the pathology. Fairly recently, the presence of a systemic OS has
      been demonstrated in RTT patients with a strong correlation with the patients'
      clinical status. The link between MECP2 mutation and the redox imbalance found in
      RTT is not clear. Animal studies have suggested a possible direct correlation
      between Mecp2 mutation and increased OS levels. In addition, the restoration of
      Mecp2 function in astrocytes significantly improves the developmental outcome of
      Mecp2-null mice and reexpression of Mecp2 gene in the brain of null mice restored
      oxidative damage, suggesting that Mecp2 loss of function can be involved in
      oxidative brain damage. Starting from the evidence that oxidative damage in the
      brain of Mecp2-null mice precedes the onset of symptoms, we evaluated whether,
      based on the current literature, the dysfunctions described in RTT could be a
      consequence or, in contrast, could be caused by OS. We also analyzed whether
      therapies that at least partially treated some RTT symptoms can play a role in
      defense against OS. At this stage we can propose that OS could be one of the main
      causes of the dysfunctions observed in RTT. In addition, the major part of the
      therapies recommended to alleviate RTT symptoms have been shown to interfere with
      oxidative homeostasis, suggesting that MeCP2 could somehow be involved in the
      protection of the brain from OS. 

PMID- 25960048
TI  - Caffeic acid attenuates rat liver reperfusion injury through sirtuin 3-dependent
      regulation of mitochondrial respiratory chain.
AB  - Sirtuin 3 (Sirt3) plays critical roles in regulating mitochondrial oxidative
      metabolism. However, whether Sirt3 is involved in liver ischemia and reperfusion
      (I/R) injury remains elusive. Caffeic acid (CA) is a natural antioxidant derived
      from Salvia miltiorrhiza. Whether CA protects against liver I/R injury through
      regulating Sirt3 and the mitochondrial respiratory chain (MRC) is unclear. This
      study investigated the effect of CA on liver I/R injury, microcirculatory
      disturbance, and potential mechanisms, particularly focusing on Sirt3-dependent
      MRC. Liver I/R of male Sprague-Dawley rats was established by occlusion of portal
      area vessels for 30 min followed by 120 min of reperfusion. CA (15 mg/kg/h) was
      continuously infused via the femoral vein starting 30 min before ischemia. After
      I/R, Sirt3 expression, and MRC activity decreased, acetylation of NADH
      dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9 and succinate
      dehydrogenase complex, subunit A, flavoprotein variant provoked, and the liver
      microcirculatory disturbance and injury were observed. Treatment with CA
      attenuated liver injury, inhibited Sirt3 down-expression, and up-regulated MRC
      activity. CA attenuated rat liver microcirculatory disturbance and oxidative
      injury through regulation of Sirt3 and the mitochondrial respiratory chain.

PMID- 25960049
TI  - Nonalcoholic fatty liver disease and cardiovascular risk in children with
      obesity.
AB  - OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) has been recognized as an
      independent risk factor for cardiovascular disease in adults. It has not been
      established whether NAFLD is related to early atherosclerotic changes in
      children. METHODS: In a cross-sectional study, 78 non diabetic, non smoking
      children with severe obesity were evaluated for NAFLD. Proton magnetic resonance
      spectroscopy was used to detect liver steatosis and serum ALT was used as a
      surrogate marker for steatohepatitis. Carotid intima-media thickness (CIMT) and
      arterial wall stiffness were measured using ultrasound. RESULTS: Steatosis was
      present in 41 (53%) of subjects. Of these children, 26 out of 41 (63%) had
      elevated ALT levels. No differences in CIMT and arterial wall stiffness were
      observed between those without and with steatosis and those with steatosis plus
      elevated ALT levels [CIMT = 0.47 (+/-0.06), 0.48 (+/-0.06) and 0.48 (+/-0.07) mm,
      respectively; stiffness = 2.78 (+/-0.50), 3.00 (+/-0.81), and 2.90 (+/-0.78),
      respectively]. Steatosis and ALT were not correlated to CIMT (r = -0.02 and 
      0.14, respectively) or arterial wall stiffness (r = 0.13 and -0.11,
      respectively). CONCLUSIONS: In this study, no relationship between NAFLD and
      early atherosclerotic changes in children was observed. An atherogenic effect of
      steatohepatitis (NASH) on pediatric age and long-term atherogenic consequences of
      simple steatosis cannot be excluded based on this study.

PMID- 25960050
TI  - Longitudinal assessment of spinal cord injuries in nonhuman primates with
      quantitative magnetization transfer.
AB  - PURPOSE: This study aimed to evaluate the reproducibility and specificity of
      quantitative magnetization transfer (qMT) imaging for monitoring spinal cord
      injuries (SCIs). METHODS: MRI scans were performed in anesthetized monkeys at
      9.4T, before and serially after a unilateral lesion of the cervical spinal cord.
      A two-pool fitting model was used to derive qMT parameters. RESULTS: qMT measures
      were reproducible across normal subjects, with an average pool size ratio (PSR)
      of 0.086 +/- 0.003 (mean +/- SD) for gray matter, and 0.120 +/- 0.005 for white
      matter, respectively. Compared with normal gray matter, the PSR of abnormal
      tissues rostral and caudal to the injury site decreased by 19.5% (P < 0.05),
      while the PSR of the cyst-like volume decreased drastically weeks after SCI.
      Strong correlations in cyst-like regions were observed between PSR and other MRI
      measures including longitudinal relaxation rate (R1 ), apparent diffusion
      coefficient and fractional anisotropy (FA). Decreased PSR and FA values
      correlated well with demyelination in abnormal tissues. CONCLUSION: The qMT
      parameters provide robust and specific information about the molecular and
      cellular changes produced by SCI. PSR detected demyelination and loss of
      macromolecules in abnormal tissue regions rostral and caudal to the cyst/lesion
      sites.

PMID- 25960052
TI  - Effectiveness of a quality improvement curriculum for medical students.
AB  - INTRODUCTION: As health systems find ways to improve quality of care, medical
      training programs are finding opportunities to prepare learners on principles of
      quality improvement (QI). The impact of QI curricula for medical students as
      measured by student learning is not well delineated. The aim of this study is to
      evaluate the effectiveness of a QI curriculum for senior medical students as
      measured by student knowledge and skills. METHODS: This study was an
      observational study that involved a self-assessment and post-test Quality
      Improvement Knowledge Application Tool (QIKAT) for intervention and control
      students. A QI curriculum consisting of online modules, live discussions,
      independent readings and reflective writing, and participation in a mentored QI
      project was offered to fourth-year medical students completing an honor's
      elective (intervention group). Senior medical students who received the standard
      QI curriculum only were recruited as controls. RESULTS: A total of 22
      intervention students and 12 control students completed the self-assessment and
      QIKAT. At baseline, there was no difference between groups in self-reported prior
      exposure to QI principles. Students in the intervention group reported more
      comfort with their skills in QI overall and in 9 of the 12 domains (p<0.05).
      Additionally, intervention students performed better in each of the three case
      scenarios (p<0.01). DISCUSSION: A brief QI curriculum for senior medical students
      results in improved comfort and knowledge with QI principles. The strengths of
      our curriculum include effective use of classroom time and faculty mentorship
      with reliance on pre-existing online modules and written resources. Additionally,
      the curriculum is easily expandable to larger groups of students and transferable
      to other institutions.

PMID- 25960053
TI  - Macrophage Cell Membrane Camouflaged Mesoporous Silica Nanocapsules for In Vivo
      Cancer Therapy.
AB  - Engineering natural macrophage cell membrane-camouflaged mesoporous silica
      nanocapsules can reduce the arrested percentage of immune cells and tissues,
      effectively prolong the survival time of nanoparticles in blood circulation
      system, and improve the accumulation in tumor. 

PMID- 25960054
TI  - Translocations involving 13q14 without associated deletion in chronic lymphoid
      leukaemia target DLEU2.

PMID- 25960055
TI  - Comparison of Hallux Interphalangeal Joint Arthrodesis Fixation Techniques: A
      Retrospective Multicenter Study.
AB  - Few studies have investigated the complications that occur after hallux
      interphalangeal joint arthrodesis. The present study evaluated complications in
      152 patients aged 18 to 80 years from 2005 to 2012 from 4 different academic
      institutions after hallux interphalangeal joint arthrodesis. Overall, 65.8% of
      the patients had >=1 complication. Infections occurred in 16.5%, dehiscence in
      12.5%, and reoperations in 27.0%. The clinical nonunion rate was >=17.8%, and the
      radiographic nonunion rate was >=13.8%. After logistic regression analysis, only
      the study site and peripheral neuropathy were associated with having >=1
      complication (p < .01 and p < .05, respectively). Single screw fixation compared
      with other fixation did not have a statistically significant influence on the
      postoperative complications. However, when fixation was expanded to 4 categories,
      single screw fixation had lower infection and reoperation rates than either
      crossed Kirschner wires or other fixation category but not compared with crossed
      screws on multivariate logistic regression analysis. Although additional studies
      are warranted, the findings from the present study might aid in both the
      prognosis of complications and the support of the use of a single screw over
      crossed Kirchner wire fixation in hallux interphalangeal joint arthrodesis. 

PMID- 25960056
TI  - Percutaneous Arthroscopic Calcaneal Osteosynthesis: A Minimally Invasive
      Technique for Displaced Intra-Articular Calcaneal Fractures.
AB  - The management of calcaneal fracture remains challenging. Open surgery has been
      fraught with high infection rates and soft tissue complications. More minimally
      invasive procedures have reduced this risk, but the patient outcomes after
      treatment of displaced calcaneal fractures have remained relatively
      unsatisfactory. We present a method for the management of Sanders grade II and
      III calcaneal fractures: percutaneous arthroscopic calcaneal osteosynthesis.
      Thirty-three fractures in 30 patients who had presented to our tertiary foot and
      ankle trauma center in central London were treated with percutaneous arthroscopic
      calcaneal osteosynthesis for calcaneal fractures, and the data were prospectively
      collected. The mean patient age at injury was 39 years. The mean follow-up period
      was 24 months. Of our patients, 58% were smokers at injury. Of the 33 fractures,
      46% were classified as grade II and 54% as grade III. The mean length of stay was
      1.92 days. At the final follow-up visit, the mean Bohler angle had increased from
      11.10 degrees  (range 2 degrees  to 24 degrees ) to 23.41 degrees  (range 15
      degrees  to 35 degrees ). The modified American Orthopaedic Foot and Ankle
      Society scale score was 72.18 (range 18 to 100), the calcaneal fracture scoring
      system score was 79.34 (range 42 to 100), and the visual analog scale score was
      29.50 (range 0 to 100). We had a single case of a superficial port site infection
      and 2 cases of prominent screws, which were removed. No cases of deep infection
      developed, and no conversion to subtalar fusion was required. This technique
      significantly reduced the incidence of postoperative wound complications. Direct
      visualization of the fracture site allowed accurate restoration of the articular
      surface and correction of heel varus. Furthermore, it was associated with a high
      self-reported functional outcome and a return to preinjury employment levels.
      Also, the results did not appear to be influenced by tobacco consumption. 

PMID- 25960051
TI  - Purinergic signaling pathways in endocrine system.
AB  - Adenosine-5'-triphosphate is released by neuroendocrine, endocrine, and other
      cell types and acts as an extracellular agonist for ligand-gated P2X cationic
      channels and G protein-coupled P2Y receptors in numerous organs and tissues,
      including the endocrine system. The breakdown of ATP by ectonucleotidases not
      only terminates its extracellular messenger functions, but also provides a
      pathway for the generation of two additional agonists: adenosine 5'-diphosphate,
      acting via some P2Y receptors, and adenosine, a native agonist for G protein
      coupled adenosine receptors, also expressed in the endocrine system. This article
      provides a review of purinergic signaling pathways in the hypothalamic
      magnocellular neurosecretory cells and neurohypophysis, hypothalamic
      parvocellular neuroendocrine system, adenohypophysis, and effector glands
      organized in five axes: hypothalamic-pituitary-gonadal, hypothalamic-pituitary
      thyroid, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-growth hormone,
      and hypothalamic-pituitary-prolactin. We attempted to summarize current knowledge
      of purinergic receptor subtypes expressed in the endocrine system, including
      their roles in intracellular signaling, hormone secretion, and other cell
      functions. We also briefly review the release mechanism for adenosine-5'
      triphosphate by neuroendocrine, endocrine and surrounding cells, the enzymes
      involved in adenosine-5'-triphosphate hydrolysis to adenosine-5'-diphosphate and
      adenosine, and the relevance of this pathway for sequential activation of
      receptors and termination of signaling. 

PMID- 25960057
TI  - Biomechanical Performance of Lateral Versus Dual Locking Plates for Calcaneal
      Fractures.
AB  - Given the high rates of wound complications with a standard lateral extensile
      incision, small dual incision techniques might result in less soft tissue
      destruction. The goal of the present study was to compare the biomechanical
      performance between a single locking plate and a dual locking plating system for
      an intra-articular calcaneal fracture model. A Sanders IIB type joint depression
      calcaneal fracture was created in 10 paired, fresh-frozen, cadaveric calcanei
      (age 47 +/- 12, range 35 to 78 years). The calcanei of each pair were randomly
      assigned for fixation using either a lateral locking reconstruction plate or
      lateral and medial locking reconstruction plates. The specimens were axially
      loaded in cyclic fashion for 1000 cycles, followed by load to failure. The
      relative fragment movement was monitored optically in both the sagittal and the
      coronal planes. The amount of overall construct displacement increased with
      cycling, although no difference was found between the plating techniques. For
      fragment movement during cycling, the lateral joint fragment migrated
      anteroinferiorly along the fracture line relative to the tuberosity fragment for
      dual plated specimens by a small, but statistically significant, amount. This
      same translation was smaller for lateral plated specimens but was not found to be
      significant. During load to failure testing, no statistically significant
      differences were found for construct stiffness. A tendency was seen toward more
      interfragmentary motion in the sagittal plane (lateral joint fragment movement
      relative to the fracture line), with less movement overall in the coronal plane
      (anterior fragment translation and twist) for dual plating, although the
      difference from the lateral plate was not statistically significant. The present
      study demonstrated that for this calcaneal fracture model, the dual plating
      technique experienced a small amount of fragment translation during cycling that
      was significantly different statistically from that with lateral plating but was
      not clinically relevant. During the load to failure, the dual plating technique
      was comparable to the lateral plate. Thus, dual plating could be a viable
      biomechanical option for fracture reduction if avoidance of a large extensile
      lateral approach associated with lateral plating is warranted. 

PMID- 25960058
TI  - Bioabsorbable Versus Metallic Screw Fixation for Tibiofibular Syndesmotic
      Ruptures: A Meta-Analysis.
AB  - Ankle fractures with syndesmotic rupture require operative treatment. In most
      cases, this consists of fixation of the tibiofibular joint with 1 or more screws.
      Bioabsorbable screws are used for the same purpose but have the advantage that
      screw removal is unnecessary. The aim of the present study was to compare the
      results of bioabsorbable and metallic syndesmotic screws. A systematic search was
      performed in the Ovid MEDLINE electronic database and Google Scholar. Three
      randomized controlled trials and one comparison study, with 260 patients, were
      included. The experimental group consisted of patients with syndesmotic injuries
      treated with bioabsorbable screws versus the control group (patients treated with
      metallic screws). The primary outcomes were complications and wound infections.
      No statistically significant difference was demonstrable in the overall number of
      complications between the 2 groups. In the group of patients with a bioabsorbable
      screw, 32 of 137 (23.4%) experienced a complication versus 7 of 123 patients
      (5.7%) with a metallic screw. Data on wound-related complications showed no
      statistically significant difference, 19.7% versus 5.7%. The average maximum
      range of motion in both groups was comparable. Bioabsorbable syndesmotic screws
      and metallic syndesmotic screws were comparable with respect to the incidence of
      complications and range of motion. However, the absolute number of complications
      was greater with bioabsorbable screws.

PMID- 25960059
TI  - Al(OH)3 facilitated synthesis of water-soluble, magnetic, radiolabelled and
      fluorescent hydroxyapatite nanoparticles.
AB  - Magnetic and fluorescent hydroxyapatite nanoparticles were synthesised using
      Al(OH)3-stabilised MnFe2O4 or Fe3O4 nanoparticles as precursors. They were
      readily and efficiently radiolabelled with (18)F. Bisphosphonate polyethylene
      glycol polymers were utilised to endow the nanoparticles with excellent colloidal
      stability in water and to incorporate cyclam for high affinity labelling with
      (64)Cu. 

PMID- 25960060
TI  - Metacarpophalangeal joint arthroscopy in the fingers other than the thumb:
      Retrospective comparison of horizontal versus vertical traction.
AB  - The goal of this study was to compare the advantages and disadvantages of
      horizontal versus vertical traction by reviewing a small series of
      metacarpophalangeal (MCP) joint arthroscopy in the fingers other than the thumb.
      Our series included eight patients operated with traction placed along the axis
      of the operated finger. In four cases, traction was applied horizontally and in
      the other four, it was applied vertically. Arthroscopy was performed using
      dorsomedial and dorsoradial portals. The fluoroscopy unit was placed either
      vertically or horizontally as required. The average duration of patient set-up
      was 17.75min in the horizontal traction group and 32min in the vertical traction
      group. The average tourniquet time was 56.75min in the horizontal traction group
      and 71min in the vertical traction group. Horizontal traction required an
      additional procedure that can potentially compromise surgical asepsis. Vertical
      traction was less comfortable for the surgeon and horizontal placement of the
      fluoroscope increased the risk of compromised asepsis. Overall, arthroscopy of
      the MCP joint of the fingers other than the thumb is an easy technique, indicated
      for trauma-related and chronic lesions, which may be best performed with
      horizontal traction. 

PMID- 25960062
TI  - Becoming a professional: What is the influence of registered nurses on nursing
      students' learning in the clinical environment?
AB  - This research was undertaken to understand the influence of registered nurses on
      nursing students' learning in the clinical environment to inform strategies to
      enable registered nurses to provide effective support to learners while also
      assisting nursing students to adopt approaches to maximise their learning in the
      clinical environment. A case study approach was applied in this research to
      explore descriptions of clinical experience of five final year nursing students.
      The student participants identified the importance of the clinical environment to
      their learning and wanted to and had actively managed their learning in the
      clinical environment. The students did not passively acquire knowledge or simply
      replicate what they observed from others. There was evidence that the students
      had strong and established perceptions of what constituted 'good' nursing and
      described an ability to discriminate between differing levels of nursing
      practice. Nursing knowledge was gained from respected registered nurses who were
      best able to describe and demonstrate the 'tricks of the trade' and 'little
      things that matter' when providing 'good' nursing. The outcomes from this
      research indicate an important role for registered nurses in both shaping nursing
      students' professional nursing identity and access to clinical learning. 

PMID- 25960061
TI  - The Spindle Assembly Checkpoint Safeguards Genomic Integrity of Skeletal Muscle
      Satellite Cells.
AB  - To ensure accurate genomic segregation, cells evolved the spindle assembly
      checkpoint (SAC), whose role in adult stem cells remains unknown. Inducible
      perturbation of a SAC kinase, Mps1, and its downstream effector, Mad2, in
      skeletal muscle stem cells shows the SAC to be critical for normal muscle growth,
      repair, and self-renewal of the stem cell pool. SAC-deficient muscle stem cells
      arrest in G1 phase of the cell cycle with elevated aneuploidy, resisting
      differentiation even under inductive conditions. p21(CIP1) is responsible for
      these SAC-deficient phenotypes. Despite aneuploidy's correlation with aging, we
      find that aged proliferating muscle stem cells display robust SAC activity
      without elevated aneuploidy. Thus, muscle stem cells have a two-step mechanism to
      safeguard their genomic integrity. The SAC prevents chromosome missegregation
      and, if it fails, p21(CIP1)-dependent G1 arrest limits cellular propagation and
      tissue integration. These mechanisms ensure that muscle stem cells with
      compromised genomes do not contribute to tissue homeostasis. 

PMID- 25960064
TI  - Narrative pedagogy with evolving case study--A transformative approach to
      gerontic nursing practice for undergraduate nursing students.
AB  - Engaging nursing students in the complexities of care across community, acute,
      rehabilitation and residential aged care settings is challenging. Equally
      challenging is conceptualising and promoting diverse and comprehensive health
      assessments across care settings that reflect clinical reality, inform clinical
      decision making, traverse theory and practice, and transform clinical practice
      knowledge. This article describes the use of narrative and evolving case study as
      a teaching-learning tool utilised by the authors in a third year undergraduate
      gerontic nursing subject in a pre-service nursing degree at a rural university.
      Principles of transformative learning and strengths based nursing were drawn upon
      in the development of the case study. The aim of the approach was to draw on
      embedded knowledge and the experiences of students and academics from assorted
      practice settings to facilitate understanding of the lived experiences of an
      older community dwelling couple. Using social learning strategies students were
      encouraged to analyse and think critically and creatively about the situations
      they were presented with. They identified possible solutions that would be
      acceptable to the couple. Building on the older couple's strengths, achievements
      and personal social capital, the aim was to develop a positive paradigm for
      health and the way older people are viewed by nursing students. 

PMID- 25960063
TI  - Primary care clinical placements: The views of Australian registered nurse
      mentors and pre-registration nursing students (part 2).
AB  - An increased burden of chronic and complex conditions treated in the community
      and an aging population have exacerbated the primary care workload. Predicted
      nursing shortages will place further stressors on this workforce. High quality
      clinical placements may provide a strategic pathway to introduce and recruit new
      nurses to this speciality. This paper is Part 2 of a two part series reporting
      the findings of a mixed methods project. Part 1 reported on the qualitative study
      and Part 2 reports on the quantitative study. Forty-five pre-registration nursing
      students from a single Australian tertiary institution and 22 primary care
      Registered Nurse (RN) mentors who supervised student learning completed an online
      survey. Students largely regarded their primary care placement positively and
      felt this to be an appropriate learning opportunity. Most RNs were satisfied with
      mentoring pre-registration nursing students in their setting. Furthermore, the
      RNs desire to mentor students and the support of general practitioners (GPs) and
      consumers were seen as key enablers of pre-registration nursing placements.
      Findings from this study provide a preliminary impression of primary care
      clinical placements from the perspective of pre-registration nursing students and
      registered nurse mentors. Further research should examine whether a broader scope
      of non-traditional health settings such as non-government organisations,
      charities, pharmacies, welfare and social services can also provide appropriate
      learning environments for pre-registration nursing students. 

PMID- 25960065
TI  - Liberalism and Public Health Ethics.
AB  - Many public health dilemmas involve a tension between the promotion of health and
      the rights of individuals. This article suggests that we should resolve the
      tension using our familiar liberal principles of government. The article
      considers the common objections that (i) liberalism is incompatible with standard
      public health interventions such as anti-smoking measures or intervention in food
      markets; (2) there are special reasons for hard paternalism in public health; and
      (3) liberalism is incompatible with proper protection of the community good. The
      article argues that we should examine these critiques in a larger methodological
      framework by first acknowledging that the right theory of public health ethics is
      the one we arrive at in reflective equilibrium. Once we examine the arguments for
      and against liberalism in that light, we can see the weaknesses in the objections
      and the strength of the case for liberalism in public health. 

PMID- 25960066
TI  - Templating growth of gold nanostructures with a CdSe quantum dot array.
AB  - In optoelectronic devices based on quantum dot arrays, thin nanolayers of gold
      are preferred as stable metal contacts and for connecting recombination centers.
      The optimal morphology requirements are uniform arrays with precisely controlled
      positions and sizes over a large area with long range ordering since this
      strongly affects device performance. To understand the development of gold layer
      nanomorphology, the detailed mechanism of structure formation are probed with
      time-resolved grazing incidence small-angle X-ray scattering (GISAXS) during gold
      sputter deposition. Gold is sputtered on a CdSe quantum dot array with a
      characteristic quantum dot spacing of ~7 nm. In the initial stages of gold
      nanostructure growth, a preferential deposition of gold on top of quantum dots
      occurs. Thus, the quantum dots act as nucleation sites for gold growth. In later
      stages, the gold nanoparticles surrounding the quantum dots undergo a coarsening
      to form a complete layer comprised of gold-dot clusters. Next, growth proceeds
      dominantly via vertical growth of gold on these gold-dot clusters to form an gold
      capping layer. In this capping layer, a shift of the cluster boundaries due to
      ripening is found. Thus, a templating of gold on a CdSe quantum dot array is
      feasible at low gold coverage. 

PMID- 25960067
TI  - Generic amyloidogenicity of mammalian prion proteins from species susceptible and
      resistant to prions.
AB  - Prion diseases are lethal, infectious diseases associated with prion protein
      (PrP) misfolding. A large number of mammals are susceptible to both sporadic and
      acquired prion diseases. Although PrP is highly conserved and ubiquitously
      expressed in all mammals, not all species exhibit prion disease. By employing
      full length recombinant PrP from five known prion susceptible species (human,
      cattle, cat, mouse and hamster) and two species considered to be prion resistant
      (pig and dog) the amyloidogenicity of these PrPs has been delineated. All the
      mammalian PrPs, even from resistant species, were swiftly converted from the
      native state to amyloid-like structure when subjected to a native condition
      conversion assay. The PrPs displayed amyloidotypic tinctorial and ultrastructural
      hallmarks. Self-seeded conversion of the PrPs displayed significantly decreased
      lag phases demonstrating that nucleation dependent polymerization is a dominating
      mechanism in the fibrillation process. Fibrils from Abeta1-40, Abeta1-42,
      Lysozyme, Insulin and Transthyretin did not accelerate conversion of HuPrP
      whereas fibrils from HuPrP90-231 and HuPrP121-231 as well as full length PrPs of
      all PrPs efficiently seeded conversion showing specificity of the assay requiring
      the C-terminal PrP sequence. Our findings have implications for PrP misfolding
      and could have ramifications in the context of prion resistant species and silent
      carriers. 

PMID- 25960068
TI  - Allergic contact dermatitis caused by adapalene.

PMID- 25960069
TI  - Defensive activation during the rubber hand illusion: Ownership versus
      proprioceptive drift.
AB  - A strong link between body perception and emotional experience has been proposed.
      To examine the interaction between body perception and anticipatory anxiety, two
      well-established paradigms were combined: The rubber hand illusion (RHI) and the
      threat-of-shock paradigm. An artificial hand and the participants' own hand
      (hidden from sight) were touched synchronously or asynchronously, while either
      threat-of-shock or safety was cued. Potentiated startle reflexes and enhanced
      skin conductance responses were observed during threat as compared to safety
      conditions, but threat conditions did not interact with illusory body
      perceptions. Thus, defense system activation was not modulated by altered body
      representations. Physiological responses increased with the sense of ownership
      for the artificial limb, but not with proprioceptive drift towards its location.
      The results indicate that ownership ratings and proprioceptive drift capture
      different aspects of the RHI. The study presents a new approach to investigate
      the relationship between body representations and emotional states. 

PMID- 25960070
TI  - Facilitated early cortical processing of nude human bodies.
AB  - Functional brain imaging has identified specialized neural systems supporting
      human body perception. Responses to nude vs. clothed bodies within this system
      are amplified. However, it remains unresolved whether nude and clothed bodies are
      processed by same cerebral networks or whether processing of nude bodies recruits
      additional affective and arousal processing areas. We recorded simultaneous MEG
      and EEG while participants viewed photographs of clothed and nude bodies. Global
      field power revealed a peak ~145ms after stimulus onset to both clothed and nude
      bodies, and ~205ms exclusively to nude bodies. Nude-body-sensitive responses were
      centered first (100-200ms) in the extrastriate and fusiform body areas, and
      subsequently (200-300ms) in affective-motivational areas including insula and
      anterior cingulate cortex. We conclude that visibility of sexual features
      facilitates early cortical processing of human bodies, the purpose of which is
      presumably to trigger sexual behavior and ultimately ensure reproduction. 

PMID- 25960071
TI  - The journey toward improved hypoplastic left heart syndrome outcomes continues-
      another small step.

PMID- 25960072
TI  - Eskimos, elephants, and endovascular: Body floss technique for hybrid arch
      procedures.

PMID- 25960073
TI  - Viewing aortic dissection through a funnel?

PMID- 25960074
TI  - Through the endovascular looking glass: Total endovascular repair for combined
      congenital and acute aortic arch disease.

PMID- 25960075
TI  - Interstitial granulomatous drug reaction induced by quetiapine.

PMID- 25960076
TI  - Theoretical study of the structures and chemical ordering of cobalt-palladium
      nanoclusters.
AB  - Global optimization of 1 : 1 compositions of (Co-Pd)N/2 up to N = 150 and all
      compositions of 34- and 38-atom binary clusters has been performed using a
      genetic algorithm, coupled with the Gupta empirical potential to model
      interatomic interactions. An ab initio approach based on density functional
      theory (DFT) has been used to reoptimize the "putative" global minimum GM
      structures for 1 : 1 compositions of (Co-Pd)N/2 up to N = 50 and all compositions
      of 34- and 38-atom binary clusters. A detailed analysis of Co-Pd structural
      motifs and segregation effects is presented. Gupta potential calculations on Co
      Pd clusters with 1 : 1 compositions have shown that the putative GM has
      Co(core)Pd(shell) segregation. A variety of structural motifs is observed for 34-
      and 38-atom CoPd clusters. From the excess energy analysis at Gupta and DFT
      level, we find different stable compositions for 34- and 38-atom CoPd clusters.
      In addition to this, low energy isomers of 38-atom (for the composition range
      Co25Pd13-Co13Pd25) clusters are also investigated at DFT level and the excess
      energies of Gupta and DFT levels are compared.

PMID- 25960077
TI  - Cutaneous apocrine carcinoma of the scrotum: A case with widespread subcutaneous
      induration.
AB  - Cutaneous apocrine carcinoma (CAC) is a rare malignancy. It develops
      predominantly in the regions where apocrine glands are distributed. Some cases of
      CAC have been reported in the axilla and the inguinal regions, but only a few in
      the scrotum. We herein report a case of CAC which widely spread over both sides
      of the whole scrotum with plate-like hard induration, and such a manifestation
      has never been reported before. CAC is known to have high rates of local
      recurrence or metastasis, and the efficacy of radiotherapy or chemotherapy has
      not been established. As therapeutic options for CAC are limited, it is critical
      to reach the diagnosis and treat at an early stage. 

PMID- 25960079
TI  - Cyclodextrins: improving the therapeutic response of analgesic drugs: a patent
      review.
AB  - INTRODUCTION: Cyclodextrins (CDs) are cyclic oligosaccharides that have recently
      been recognized as useful tools for optimizing the delivery of such problematic
      drugs. CDs can be found in at least 35 pharmaceutical products, such as
      anticancer agents, analgesic and anti-inflammatory drugs. Besides, several
      studies have demonstrated that CD-complexed drugs could provide benefits in
      solubility, stability and also improve pharmacological response when compared
      with the drug alone. AREAS COVERED: The patent search was conducted in the
      databases WIPO, Espacenet, USPTO, Derwent and INPI, using the keywords
      cyclodextrin, pain and its related terms (analgesia, hyperalgesia,
      hypernociception, nociception, antinociception, antinociceptive). We found 442
      patents. Criteria such as the complexation of analgesic agents and evidence of
      improvement of the therapeutic effect were indispensable for the inclusion of the
      patent. So, 18 patents were selected. EXPERT OPINION: We noticed that some
      patents are related to the complexation of opioids, NSAIDs, as well as natural
      products, in different types of CDs. The use of CDs creates the prospect of
      developing new therapeutic options for the most effective treatment of painful
      conditions, allowing a reduction of dosage of analgesic drugs and the occurrence
      of side effects. Thus, CDs can be an important tool to improve the efficacy and
      pharmacological profile of analgesic drugs.

PMID- 25960080
TI  - Body mass index and early CD4 T-cell recovery among adults initiating
      antiretroviral therapy in North America, 1998-2010.
AB  - OBJECTIVES: Adipose tissue affects several aspects of the cellular immune system,
      but prior epidemiological studies have differed on whether a higher body mass
      index (BMI) promotes CD4 T-cell recovery on antiretroviral therapy (ART). The
      objective of this analysis was to assess the relationship between BMI at ART
      initiation and early changes in CD4 T-cell count. METHODS: We used the North
      American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) data set to
      analyse the relationship between pre-treatment BMI and 12-month CD4 T-cell
      recovery among adults who started ART between 1998 and 2010 and maintained HIV-1
      RNA levels < 400 copies/mL for at least 6 months. Multivariable regression models
      were adjusted for age, race, sex, baseline CD4 count and HIV RNA level, year of
      ART initiation, ART regimen and clinical site. RESULTS: A total of 8381
      participants from 13 cohorts contributed data; 85% were male, 52% were nonwhite,
      32% were overweight (BMI 25-29.9 kg/m(2) ) and 15% were obese (BMI > 30 kg/m(2)
      ). Pretreatment BMI was associated with 12-month CD4 T-cell change (P < 0.001),
      but the relationship was nonlinear (P < 0.001). Compared with a reference of 22
      kg/m(2) , a BMI of 30 kg/m(2) was associated with a 36 cells/MUL [95% confidence
      interval (CI) 14, 59 cells/MUL] greater CD4 T-cell count recovery among women and
      a 19 cells/MUL (95% CI 9, 30 cells/MUL) greater recovery among men at 12 months.
      At a BMI > 30 kg/m(2) , the observed benefit was attenuated among men to a
      greater degree than among women, although this difference was not statistically
      significant. CONCLUSIONS: A BMI of approximately 30 kg/m(2) at ART initiation was
      associated with greater CD4 T-cell recovery at 12 months compared with higher or
      lower BMI values, suggesting that body composition may affect peripheral CD4 T
      cell recovery.

PMID- 25960082
TI  - The inhibitory effects of corncob bedding on sexual behavior in the
      ovariectomized Long-Evans rat treated with estradiol benzoate are overcome by
      male cues.
AB  - The mechanisms underlying the sensitization of sexual behaviors by repeated
      administration of estradiol benzoate (EB) to ovariectomized (OVX) rats are not
      well understood. Here we tested whether two housing conditions play a role.
      Sexual behavior in the female rat is dependent on the activation of ERalpha
      (estrogen receptor alpha) by estradiol. Corncob (CC) bedding has been reported to
      have adverse effects on the reproductive behavior and physiology of rats, and to
      disrupt ERalpha signaling in mice. In addition, some rodent behaviors are
      stimulated by olfactory stimuli and enhanced in the presence of estradiol. Upon
      arrival to the facilities OVX Long-Evans rats were housed on either Sani-Chips
      (SC) or CC in a room that housed only females (F) or males and females (M).
      Females were first given four sexual training sessions with 10 MUg EB + 500 MUg
      progesterone (P; administered 48 h and 4h prior to training, respectively),
      followed by a 2-week hormone washout period. Next, 10 MUg EB was administered
      s.c. every 4 days, 48 h prior to each of 8 test sessions in a unilevel 4-hole
      pacing chamber. On the final training day (i.e., when primed with EB+P), no
      inhibitory effects of corncob bedding were found, however a facilitation of the
      lordosis quality occurred in SC/F. Although all groups appear to have sensitized
      to the repeated administration of EB, CC/F animals displayed fewer high quality
      lordosis magnitudes and hop/darts, and received fewer mounts and intromissions
      overall. They also had a lower lordosis quotient (LQ) on tests 2-4 although this
      effect disappeared by test 5. These results suggest that although CC may inhibit
      some components of female sexual behavior when primed with EB alone, cues from
      sexually vigorous males can overcome that inhibition. Moreover, they suggest that
      male cues can facilitate mechanisms of estradiol sensitization. We recommend that
      quality control studies be conducted at individual institutions to assess any
      impact of corncob bedding on animal physiology and behavior.

PMID- 25960083
TI  - Impact of variation in structure of condensed tannins from sainfoin (Onobrychis
      viciifolia) on in vitro ruminal methane production and fermentation
      characteristics.
AB  - Our study investigated the effects of condensed tannins (CT) on rumen in vitro
      methane (CH4 ) production and fermentation characteristics by incubating lucerne
      in buffered rumen fluid in combination with different CT extracts at 0 (control),
      40, 80 and 120 g CT/kg of substrate DM. Condensed tannins were extracted from
      four sainfoin accessions: Rees 'A', CPI63763, Cotswold Common and CPI63767. Gas
      production (GP) was measured using a fully automated GP apparatus with CH4
      measured at distinct time points. Condensed tannins differed substantially in
      terms of polymer size and varied from 13 (Rees 'A') to 73 (CPI63767) mean degree
      of polymerization, but had relatively similar characteristics in terms of CT
      content, procyanidin: prodelphinidin (PC: PD) and cis:trans ratios. Compared to
      control, addition of CT from CPI63767 and CPI63763 at 80 and 120 g CT/kg of
      substrate DM reduced CH4 by 43% and 65%, and by 23% and 57%, respectively, after
      24-h incubation. Similarly, CT from Rees 'A' and Cotswold Common reduced CH4 by
      26% and 46%, and by 28% and 46% respectively. Addition of increasing level of CT
      linearly reduced the maximum rates of GP and CH4 production, and the estimated in
      vitro organic matter digestibility. There was a negative linear and quadratic (p
      < 0.01) relation between CT concentration and total volatile fatty acid (VFA)
      production. Inclusion of 80 and 120 g CT/kg of substrate DM reduced (p < 0.001)
      branched-chain VFA production and acetate: propionate ratio and was lowest for
      CPI63767. A decrease in proteolytic activity as indirectly shown by a change in
      VFA composition favouring a shift towards propionate and reduction in branched
      chain VFA production varied with type of CT and was highest for CPI63767. In
      conclusion, these results suggest that tannin polymer size is an important factor
      affecting in vitro CH4 production which may be linked to the CT interaction with
      dietary substrate or microbial cells. 

PMID- 25960081
TI  - Molecular mechanisms underlying the memory-enhancing effects of estradiol.
AB  - This article is part of a Special Issue "Estradiol and cognition". Since the
      publication of the 1998 special issue of Hormones and Behavior on estrogens and
      cognition, substantial progress has been made towards understanding the molecular
      mechanisms through which 17beta-estradiol (E2) regulates hippocampal plasticity
      and memory. Recent research has demonstrated that rapid effects of E2 on
      hippocampal cell signaling, epigenetic processes, and local protein synthesis are
      necessary for E2 to facilitate the consolidation of object recognition and
      spatial memories in ovariectomized female rodents. These effects appear to be
      mediated by non-classical actions of the intracellular estrogen receptors ERalpha
      and ERbeta, and possibly by membrane-bound ERs such as the G-protein-coupled
      estrogen receptor (GPER). New findings also suggest a key role of hippocampally
      synthesized E2 in regulating hippocampal memory formation. The present review
      discusses these findings in detail and suggests avenues for future study. 

PMID- 25960084
TI  - ALSUntangled No. 28: Acupuncture.

PMID- 25960085
TI  - A single blind randomized controlled clinical trial of mexiletine in amyotrophic
      lateral sclerosis: Efficacy and safety of sodium channel blocker phase II trial.
AB  - Fasciculations are characteristic features of amyotrophic lateral sclerosis
      (ALS), and suggest motor nerve hyperexcitability. Recent reports have shown that
      an increase in persistent nodal sodium current is associated with shorter
      survival in ALS patients. This objective of this trial is to study the efficacy
      and safety of mexiletine, a sodium channel blocker, for ALS. Sixty eligible
      participants were randomly allocated (1:1) to riluzole 100 mg or riluzole plus
      mexiletine 300 mg. The primary endpoint was change in the revised ALS functional
      rating scale (ALSFRS-R) scores during six months. We also monitored strength
      duration time constant (SDTC, a measure of persistent sodium current) in median
      motor axons. Results showed that during six months of treatment, changes in the
      ALSFRS-R score and SDTC were -7.0 +/- 7.1 and -0.04 +/- 0.1, respectively, in the
      riluzole group and -6.9 +/- 6.4 and 0.04 +/- 0.1, respectively, in the mexiletine
      group (p = 0.96 and 0.049). Adverse events amounted 20% in the riluzole and 33%
      in the mexiletine groups. In conclusion, the results suggest that daily 300 mg
      mexiletine has no effects on axonal sodium current and ALSFRS-R deterioration in
      ALS. We have to attempt another trial using a higher dose of mexiletine or other
      agents to suppress sodium currents and ALS progression in the future. 

PMID- 25960086
TI  - Whole genome analyses reveal no pathogenetic single nucleotide or structural
      differences between monozygotic twins discordant for amyotrophic lateral
      sclerosis.
AB  - The contribution of genetic and environmental factors to the pathogenesis of
      sporadic amyotrophic lateral sclerosis (ALS) remains unclear. To investigate the
      genetic component of the disease, we performed whole genome sequencing on ALS
      discordant monozygotic twins. Illumina whole genome sequencing on white blood
      cell DNA of five ALS-discordant monozygotic twin pairs (10 samples in total)
      yielded ~30x coverage per individual. All single nucleotide variants, indels, and
      structural variants (copy number variants, inversions and translocations) were
      called and evaluated for functional consequence, evolutionary conservation,
      population frequency and overlap with known ALS associated variants and genes.
      Results showed that no validated discordant coding or regulatory single
      nucleotide variants or indels were found, and nor were any genome-wide discordant
      structural variants detected. Concordant variants of particular interest were: 1)
      two rare, highly-conserved heterozygous non-synonymous variants in SYT9 and
      EWSR1, genes previously associated with ALS (out of 2044 rare heterozygous
      variants detected); 2) three rare homozygous missense variants; and 3) three
      novel copy number deletions that overlapped genes. In conclusion, no convincing
      coding or regulatory nucleotide or genome-wide structural differences were found
      between ALS discordant monozygotic twins. The results suggest that more work is
      needed to elucidate possible environmental, epigenetic, oligogenic and somatic
      genetic factors that could underlie susceptibility to sporadic ALS. 

PMID- 25960087
TI  - The histone deacetylase sirtuin 2 is a new player in the regulation of platelet
      function.
AB  - BACKGROUND: Histone deacetylases (HDACs) play a key role in signaling in many
      cell types. However, little is known about the participation of HDACs,
      particularly sirtuins (SIRTs), in platelet reactivity. OBJECTIVE: To investigate
      the role of HDACs in platelets, we examined the effects of SIRT inhibition on
      platelet function and protein acetylation in human platelets. METHODS: We used
      washed platelets obtained from healthy subjects. Cambinol (SIRT1 and SIRT2
      inhibitor), AGK2 (specific SIRT2 inhibitor) and EX527 (specific SIRT1 inhibitor)
      were used as SIRT inhibitors. Platelets were stimulated with collagen, thrombin,
      or U46619, and platelet responses were determined according to optical
      aggregometry findings, dense granule release, and cytosolic calcium levels (Fura
      2AM fluorescence). Protein acetylation and phosphorylation were assessed by
      immunoblotting. RESULTS: SIRT inhibition remarkably reduced platelet responses
      (aggregation, granule release, and cytosolic calcium level; P < 0.05). SIRT2 was
      present in platelets at the level of mRNA and protein, and its specific
      inhibition reduced platelet responses. The acetylated protein pattern observed in
      resting platelets changed during platelet aggregation. Inhibition of SIRT2
      increased the acetylation of Akt kinase, which in turn blocked agonist-induced
      Akt phosphorylation and glycogen synthase kinase-3beta phosphorylation, which are
      markers of Akt activity. Finally, collagen-induced aggregation provoked Akt
      acetylation. CONCLUSIONS: Regulation of protein acetylation by SIRT2 plays a
      central role in platelet function. The effects of SIRT2 are mediated in part by
      the acetylation and inhibition of Akt. These results open a new avenue for
      research into the control of platelet function, and may help to identify new
      therapeutic targets.

PMID- 25960088
TI  - Brain size affects female but not male survival under predation threat.
AB  - There is remarkable diversity in brain size among vertebrates, but surprisingly
      little is known about how ecological species interactions impact the evolution of
      brain size. Using guppies, artificially selected for large and small brains, we
      determined how brain size affects survival under predation threat in a
      naturalistic environment. We cohoused mixed groups of small- and large-brained
      individuals in six semi-natural streams with their natural predator, the pike
      cichlid, and monitored survival in weekly censuses over 5 months. We found that
      large-brained females had 13.5% higher survival compared to small-brained
      females, whereas the brain size had no discernible effect on male survival. We
      suggest that large-brained females have a cognitive advantage that allows them to
      better evade predation, whereas large-brained males are more colourful, which may
      counteract any potential benefits of brain size. Our study provides the first
      experimental evidence that trophic interactions can affect the evolution of brain
      size.

PMID- 25960089
TI  - (Anti)mutagenic and immunomodulatory properties of quercetin glycosides.
AB  - BACKGROUND: Quercetin-3-O-beta-D-glucopyranoside (isoquercitrin) and quercetin-3
      O-rutinoside (rutin) are common components of a normal human diet and are
      increasingly used in food supplements. Here their effect on mutagenesis and
      immunity is shown. RESULTS: The in vitro (anti)mutagenic potential was compared
      with that of quercetin using the Ames test in Salmonella typhimurium His(-)
      strains TA100, TA98 and TA102. Isoquercitrin only slightly increased the number
      of revertants, while rutin was totally non-mutagenic. On the other hand, all
      compounds displayed dose-dependent protective activity against H2O2 - and tert
      butyl hydroperoxide-induced oxidative damage to the TA102 strain and at 75 umol
      L(-1) inhibited H2O2/Fe(2+)-induced formation of the open circular and linear
      forms of the DNA plasmid pBSIISK(-). In mice, none of the flavonols (0.86 umol
      day(-1), 34 days) induced harmful effects. In immunized animals, all compounds
      enhanced ex vivo B cell proliferation; quercetin stimulated lymphocyte basal
      proliferation and increased the number of IgM-producing lymphocytes. Rutin
      promoted NK cytotoxic activity, supported T cells and enhanced gut epithelium
      renewal. No effect on IgG-forming cells was found. CONCLUSION: Isoquercitrin
      displayed negligible and rutin no mutagenicity, but both showed significant
      antimutagenic and DNA-protective effects against oxidative damage. In vivo, they
      supported the readiness of the immune system for specific humoral immune
      response.

PMID- 25960090
TI  - Tropical medicine in the era of global connectivity.

PMID- 25960091
TI  - Immigrant Populations: Global Health in our Backyard.

PMID- 25960093
TI  - Transmission of ebola virus disease: an overview.
AB  - Ebola is a viral illness of which the initial symptoms can include a sudden
      fever, intense weakness, muscle pain and a sore throat, according to the World
      Health Organization (WHO). Airborne transmission of Ebola virus has been
      hypothesized but not demonstrated in humans. Ebola is not spread through the air
      or by water, or in general, by food. However, in Africa, Ebola may be spread as a
      result of handling bushmeat (wild animals hunted for food) and contact with
      infected bats. The disease infects humans through close contact with infected
      animals, including chimpanzees, fruit bats, and forest antelope. Ebola virus can
      be transmitted by direct contact with blood, bodily fluids, or skin of patients
      with or who died of Ebola virus disease. As of late October 2014, the World
      Health Organization reported 13,567 suspected cases and 4922 deaths, although the
      agency believes that this substantially understates the magnitude of the
      outbreak. Experimental vaccines and treatments for Ebola are under development,
      but they have not yet been fully tested for safety or effectiveness.

PMID- 25960092
TI  - Assessing 15 proposals for promoting innovation and access to medicines globally.
AB  - BACKGROUND: There is widespread recognition that the existing global systems for
      innovation and access to medicines need reform. Billions of people do not have
      access to the medicines they need, and market failures prevent new drugs from
      being developed for diseases that primarily affect the global poor. The World
      Health Organization's Consultative Expert Working Group on Research and
      Development: Financing and Coordination (CEWG) analyzed numerous proposals for
      reform. The aim of this article is to build on these previous inquiries. METHODS:
      We conducted a structured analysis that grouped proposals into five broad
      opportunities for global policy reform to help researchers and decision makers to
      meaningfully evaluate each proposal in comparison with similar proposals.
      Proposals were also analyzed along three important dimensions-potential health
      impact, financial implications, and political feasibility-further facilitating
      the comparison and application of this information. FINDINGS: Upon analysis, no
      one solution was deemed a panacea, as many (often competing) considerations need
      to be taken into account. However, some proposals, particularly product
      development partnership and prizes, appeared more promising and feasible at this
      time and deserve further attention. CONCLUSION: More research is needed into the
      effectiveness of these mechanisms and their transferability across jurisdictions.

PMID- 25960094
TI  - How prepared are Nigerian schools for ebola virus disease prevention and control?
AB  - BACKGROUND: Nigeria was one of the West African countries gripped by the fear of
      the spread of the Ebola virus disease (EVD), leading to a long period of delay in
      resumption of primary and secondary schools for academic activities in September
      2014. The aim of this study was to assess the preparedness of schools in the
      north central region of Nigeria toward EVD prevention and control within 1 month
      of resumption of schools. METHODS: This was a descriptive cross-sectional study
      among 76 schools selected using a multistage sampling method. Research
      instruments were self-administered, semi-structured questionnaires. Data was
      analyzed using the SPSS software version 17.0. FINDINGS: Half (38) of the schools
      reported that some of the children could have traveled to EVD-infected areas
      during the holiday period; 77.6% (59) had their teachers formally trained on EVD
      prevention and control before resumption; 50% (38) set up a committee on EVD
      prevention; and 62.9% (63) carried out awareness-raising activities on school
      assembly ground. Based on some preventive measures criteria, 55.2% (42) were
      categorized ready, whereas 44.7% (34) were not ready for EVD prevention and
      control within 1 month of resumption of students back to school. About 76.3% (58)
      said they would like to sustain these EVD prevention efforts; 14.5% (11) would
      like to sustain such efforts at least until the end of the present term.
      Determinants of readiness for EVD prevention and control include being a private
      school, being an urban school, belief that children could have traveled to an EVD
      infected area, and school having standard operating procedure or policy
      guidelines on EVD prevention and control. CONCLUSION: The persistent call for
      postponement of school resumption might have been due to the unpreparedness of
      many of schools to meet EVD prevention and control guidelines. Schools need to
      take more proactive and sustainable measures toward effective control of the
      ongoing epidemic and prevention of future occurrences.

PMID- 25960095
TI  - Malaria and macronutrient deficiency as correlates of anemia in young children: a
      systematic review of observational studies.
AB  - BACKGROUND: Anemia is a leading cause of pediatric mortality and impaired
      development and is highly prevalent in young children in sub-Saharan Africa.
      Populations most affected by anemia also often are at high risk for malaria and
      macronutrient deficiency, conditions that may exacerbate anemia. Due to its
      multifactorial etiology, anemia presents a significant global health challenge,
      and successful interventions targeting anemia require a greater understanding of
      the relative and interacting contributions of malaria and undernutrition.
      OBJECTIVES: The aim of this study was to assess the associations of malaria and
      undernutrition, indicated by stunting and wasting, with anemia in young children
      using a systematic review of observational studies. METHODS: Searches were
      conducted in MEDLINE and Scopus. Articles were screened and reviewed for
      inclusion by two reviewers. Studies published after 1990 that measured anemia,
      Plasmodium falciparum malaria, and stunting or wasting in children aged 5 years
      or under were included. FINDINGS: Of 620 articles reviewed, 15 studies from 9
      countries in sub-Saharan Africa were included. Statistical approaches and anemia
      measurement varied widely, so synthesis was qualitative. Thirteen studies found
      that malaria infection was associated with anemia or lowered hemoglobin; in these
      studies, malaria accounted for more of the variation in anemia than nutritional
      status. In contrast, only 7 of the 13 studies investigating stunting and 3 of the
      6 studies investigating wasting as correlates of anemia observed statistically
      significant associations at alpha = 0.05. The role of nutrition in anemia may
      differ by country. CONCLUSIONS: Observational epidemiologic studies consistently
      demonstrate that malaria is an important correlate of anemia in young children;
      however, the roles of stunting and wasting and interactions between malaria and
      nutrition require further investigation. Based on the current evidence, these
      findings suggest that global health strategies to reduce the burden of anemia
      should prioritize malaria prevention and support research on alternative causes
      of anemia that reflect local conditions.

PMID- 25960097
TI  - Molecular Diagnosis of TB in the HIV Positive Population.
AB  - BACKGROUND: Tuberculosis (TB) remains a major contributor to morbidity and
      mortality in HIV-positive individuals, causing 1.1 million incident cases and
      0.32 million deaths in 2012. Diagnosis of TB is particularly challenging in HIV
      coinfected individuals, due to a high frequency of smear-negative disease,
      atypical presentations, and extrapulmonary TB. OBJECTIVE: The aim of this article
      was to review the current literature on molecular diagnostics for TB with an
      emphasis on the performance of these diagnostic tests in the HIV-positive
      population. METHODS: We searched the PubMed database using at least one of the
      terms TB, HIV, diagnostics, Xpert MTB/RIF, nucleic acid amplification tests, drug
      susceptibility testing, RNA transcription, and drew on World Health Organization
      publications. FINDINGS: With increased focus on reducing TB prevalence worldwide,
      a new set of tools for diagnosing the disease have emerged. Molecular tools such
      as Xpert MTB/RIF and line-probe assays are now in use or are being rolled out in
      many regions. The diagnostic performance of these and other molecular assays are
      discussed here as they pertain to the HIV-positive population. CONCLUSIONS:
      Molecular diagnostics offer a useful addition and at times, alternative, to
      traditional culture methods for the diagnosis of TB. However, most of these tests
      suffer from decreased accuracy in the HIV-positive population.

PMID- 25960099
TI  - Beating the odds in Uganda.

PMID- 25960096
TI  - The burden of dengue and chikungunya worldwide: implications for the southern
      United States and California.
AB  - BACKGROUND: Dengue virus (DENV) spreads to humans through the bite of an infected
      Aedes aegypti or Aedes albopictus mosquito and is a growing public health threat
      to both industrialized and developing nations worldwide. Outbreaks of
      autochthonous dengue in the United States occurred extensively in the past but
      over the past 3 decades have again taken place in Florida, Hawaii, and Texas as
      well as in American Samoa, Guam, Northern Mariana Islands, Puerto Rico, and the
      US Virgin Islands. As the Aedes vectors spread worldwide it is anticipated that
      DENV as well as other viruses also transmitted by these vectors, such as
      Chikungunya virus (CHKV), will invade new areas of the world, including the
      United States. OBJECTIVES: In this review, we describe the current burden of
      dengue disease worldwide and the potential introduction of DENV and CHKV into
      different areas of the United States. Of these areas, the state of California saw
      the arrival and spread of the Aedes aegypti vector beginning in 2013. This
      invasion presents a developing situation when considering the state's number of
      imported dengue cases and proximity to northern Mexico as well as the rising
      specter of chikungunya in the Western hemisphere. FINDINGS: In light of the
      recent arrival of Aedes aegypti mosquito vectors to California, there is now a
      small but appreciable risk for endemic transmission of dengue and chikungunya
      within the State. It is likely, however, that if DENV or CHKV were to become
      endemic that the public health situation would be similar to that currently found
      along the Texas-Mexico border. The distribution of Aedes vectors in California as
      well as a discussion of several factors contributing to the risk for dengue
      importation are discussed and evaluated. CONCLUSIONS: Dengue and chikungunya
      viruses present real risks to states where the Aedes vector is now established.
      Scientists, physicians, and public health authorities should familiarize
      themselves with these risks and prepare appropriately.

PMID- 25960100
TI  - One-pot synthesis of high-performance Co/graphene electrocatalysts for glucose
      fuel cells free of enzymes and precious metals.
AB  - A facile recipe has been developed to prepare three-dimensional nanoarchitectures
      of nitrogen-doped graphene loading Co nanoparticle hybrids (Co/NG). The hybrids
      show an outstanding electrocatalytic activity for glucose oxidation reaction
      (GOR) and oxygen reduction reaction (ORR), and thus can be used as electrode
      materials of a nonenzymatic and precious-metal-free glucose fuel cell (GFC). 

PMID- 25960098
TI  - Sexually transmitted disease syndromic case management through public sector
      facilities: development and assessment study in Punjab Pakistan.
AB  - OBJECTIVE: Sexually transmitted infections (STIs) are a priority health problem.
      We proposed a prospective study in two districts of Punjab, using an intervention
      package, which included guidelines and protocols on syndrome-based management of
      STIs, adapted in light of technical guidelines from the National AIDS Control
      Program and the World Health Organization. The aim of this study was to assess
      the operational effectiveness of STI case management guidelines and to assess
      factors that determine the adherence to guidelines for management of STIs at
      public health facilities in Pakistan. METHODS: A prospective study lasting 18
      months (January 2008 to June 2009), which reviewed early implementation
      experiences of updated case management guidelines for delivery of syndrome-based
      STI/reproductive tract infection care, through public-sector health care
      facilities. The project was implemented in two districts of Punjab, Sargodha and
      Jhang. A Cox regression model with stratification was done. FINDINGS: The
      prevalence of STI was 26 per 100,000 patients. In women, the reported symptoms
      were 80% vaginal discharge and 12% abdominal pain. Forty-four percent of men had
      a genital ulcer and 29% of men had genital discharge. Age of participants ranged
      from 13 to 60 years. The study comprised 28.6% men and 71.4% women. The majority
      of the population attending these clinics was from rural areas (70%). The
      variables independently associated with adherence to guidelines were availability
      of male paramedic, age of patient, and type of diagnosis made. There was an
      important interaction (effect modification) present between the area of health
      facility and patient sex. CONCLUSION: Screening, diagnosis, and treatment costs
      for many STIs are expensive and thus an easier, low-cost, syndrome-based public
      health strategy is the adoption of the proposed STI syndrome case management
      guidelines.

PMID- 25960101
TI  - Acceptor reactivity in the total synthesis of alginate fragments containing alpha
      L-guluronic acid and beta-D-mannuronic acid.
AB  - The total synthesis of mixed-sequence alginate oligosaccharides, featuring both
      beta-D-mannuronic acid (M) and alpha-L-guluronic acid (G), is reported for the
      first time. A set of GM, GMG, GMGM, GMGMG, GMGMGM, GMGMGMG, and GMGGMG alginates
      was assembled using GM building blocks, having a guluronic acid acceptor part and
      a mannuronic acid donor side to allow the fully stereoselective construction of
      the cis-glycosidic linkages. It was found that the nature of the reducing-end
      anomeric center, which is ten atoms away from the reacting alcohol group in the
      key disaccharide acceptor, had a tremendous effect on the efficiency with which
      the building blocks were united. This chiral center determines the overall shape
      of the acceptor and it is revealed that the conformational flexibility of the
      acceptor is an all-important factor in determining the outcome of a glycosylation
      reaction. 

PMID- 25960102
TI  - The revolutionary studies by Leonardo on blood circulation were too advanced for
      his times to be published.

PMID- 25960103
TI  - sigma-Hole...pi and lone pair...pi interactions in benzylic halides.
AB  - Intermolecular and intramolecular halogen...pi interactions in benzylic halides
      (Ph-CR2-X; X = F, Cl, Br and I) derived from 7-phenylnorbornane were
      investigated. The imposed geometry of the 7-arylnorbornane moiety prevents the
      participation of intramolecular attractive interactions between the sigma-hole
      region of the halogen atom and the pi electrons of the aromatic ring.
      Crystallographic data show intermolecular halogen bonds in iodide 1 and bromide 2
      in the solid state. On the other hand, both UV-Vis and D-NMR data suggest the
      occurrence of intramolecular interactions between the halogen atoms and the
      phenyl rings in these compounds in solution. To provide more insight into the
      nature of the observed stabilizing interactions, density functional calculations
      were also carried out. These computations confirm the presence of genuine lone
      pairpi intramolecular interactions which strongly affect the stability and the
      electronic structure of these species.

PMID- 25960104
TI  - Experimental gingivitis, bacteremia and systemic biomarkers: a randomized
      clinical trial.
AB  - BACKGROUND AND OBJECTIVE: Bacteremia and systemic inflammatory markers are
      associated with periodontal and systemic diseases and may be linking mechanisms
      between these conditions. We hypothesized that in the development of gingival
      inflammation, systemic markers of inflammation and bacteremia would increase.
      MATERIAL AND METHODS: To study the effect of bacteremia on systemic inflammatory
      markers, we recruited 80 subjects to participate in an experimental gingivitis
      study. Subjects were stratified based on gender, smoking and the number of
      bleeding sites and then randomized to one of two groups: control group (n = 40)
      or experimental gingivitis group (n = 40). Subjects in the control group
      conducted an oral hygiene regimen: brushing twice daily with a regular sodium
      fluoride cavity protection dentifrice and a standard manual toothbrush, flossing
      twice daily, and mouth rinsing with an anti-cavity fluoride rinse once daily. The
      experimental group stopped brushing and flossing, and used only the fluoride anti
      cavity mouth rinse for 21 d. RESULTS: Seventy-nine of 80 subjects were evaluable.
      One subject in the control group was excluded from the results due to antibiotic
      use during the study. Our data showed the experimental gingivitis group exhibited
      a significant (p < 0.05) increase in dental plaque level and gingival
      inflammatory indices relative to baseline and the control group but a decrease in
      bacteremia and soluble intercellular adhesion molecule-1 levels vs. baseline.
      Bacteremia was negatively correlated with gingival inflammatory indices and
      soluble intercellular adhesion molecule-1 levels in the experimental gingivitis
      group, thus negating our hypothesis. CONCLUSION: We conclude that there are
      marked differences in systemic cytokine levels over the course of short-term
      experimentally induced gingivitis and further conclude that a long-term
      periodontitis study must be considered to address mechanisms whereby oral
      diseases may affect systemic diseases.

PMID- 25960105
TI  - Genetic identities and local inbreeding in pure diploid clones with homoplasic
      markers: SNPs may be misleading.
AB  - Expected values for observed heterozygosity, genetic diversity, and inbreeding of
      individuals relative to inbreeding of the population (F(IS)) are derived in the
      case of one locus displaying homoplasy with K possible allelic states (KAM model)
      in a clonal diploid population. Heterozygosity (H(O)) and genetic diversity
      (H(S)) are substantially affected by homoplasy as long as the number of alleles K
      ? 10, while F(IS) remains weakly affected in any case. Simulations suggest that
      in big populations, or in case of maximum homoplasy (K = 2), expected values can
      appear far from the observed ones because equilibrium takes too many generations
      to be reached at homoplasic markers in clonally propagating populations. This
      raises some concern on the use of SNPs, at least in clonal populations.

PMID- 25960106
TI  - Clinical Practice Guidelines for Breast Cancer: Current Limitations.

PMID- 25960107
TI  - Factors affecting the probability of bacteriological cure of bovine mastitis.
AB  - The aim of this study was to review factors affecting the probability of cure of
      bovine mastitis and thereby establish criteria for deciding whether to treat or
      cull individual animals. A further objective was to avoid redundant treatment
      with antibiotics so as to reduce the risk of pathogen resistance and enhance
      economic benefit. In evaluating success of therapy, bacteriological cure is the
      standard type of cure and is defined as elimination of mastitis-causing pathogens
      from the mammary gland. Administration of antibiotics is considered reasonable
      only when there is a prospect of bacteriological cure. In addition to age of the
      affected cow, the history of mastitis, number of infected quarters and somatic
      cell count affect the probability of bacteriological cure. Identifying and
      characterising chronic mastitis, which causes enormous production losses, are
      especially important to prevent unnecessary treatment and to decide whether or
      not to cull. To our knowledge, this is the first work providing a complete list
      of factors that have been confirmed in scientific literature to influence the
      probability of cure. This review should support farmers and veterinarians in
      deciding between culling and administering appropriate therapy to an affected
      animal. 

PMID- 25960108
TI  - Probing the Cl--pumping photocycle of pharaonis halorhodopsin: Examinations with
      bacterioruberin, an intrinsic dye, and membrane potential-induced modulation of
      the photocycle.
AB  - Halorhodopsin (HR) functions as a light-driven inward Cl- pump. The Cl- transfer
      process of HR from Natronomonas pharaonis (NpHR) was examined utilizing a mutant
      strain, KM-1, which expresses large amount of NpHR in a complex with the
      carotenoid bacterioruberin (Brub). When Cl- was added to unphotolyzed Cl--free
      NpHR-Brub complex, Brub caused the absorption spectral change in response to the
      Cl- binding to NpHR through the altered electrostatic environment and/or
      distortion of its own configuration. During the Cl--puming photocycle, on the
      other hand, oppositely directed spectral change of Brub appeared during the O
      intermediate formation and remained until the decay of the last intermediate
      NpHR'. These results indicate that Cl- is released into the cytoplasmic medium
      during the N to O transition, and that the subsequent NpHR' still maintains an
      altered protein conformation while another Cl- already binds in the vicinity of
      the Schiff base. Using the cell envelope vesicles, the effect of the interior
      negative membrane potential on the photocycle was examined. The prominent effect
      appeared in the shift of the N-O quasi-equilibrium toward N, supporting Cl-
      release during the N to O transition. The membrane potential had a much larger
      effect on the Cl- transfer in the cytoplasmic half channel compared to that in
      the extracellular half channel. This result may reflect the differences in
      dielectric constants and/or lengths of the pathways for Cl- transfers during N to
      O and O to NpHR' transitions.

PMID- 25960109
TI  - Taking the pulse of atrial fibrillation.

PMID- 25960111
TI  - Delayed consent: will there be a shift in approach for US primary percutaneous
      coronary intervention trials?

PMID- 25960112
TI  - Extremely severe anaemia in a critically ill patient who declined a blood
      transfusion.

PMID- 25960113
TI  - An evaluation of expectant parents knowledge, satisfaction and use of a self
      instructional infant CPR kit.
AB  - OBJECTIVE: in many parts of Europe as in Ireland, maternity services do not
      provide infant CPR training routinely to expectant or new parents. Little is
      known of the views of expectant women and their partners about learning the
      skills of infant CPR as part of their antenatal education. The aim of this study
      was to evaluate knowledge, satisfaction and use of a 22 minute Self-Instructional
      Infant CPR kit to facilitate the teaching of infant CPR and the relief of choking
      in an infant. METHODS: expectant women with their partners were recruited through
      the antenatal education classes from one maternity hospital in Ireland. An
      uncontrolled pre-post-test design was used and participants were surveyed
      immediately pre- and post-training and six months following training. FINDINGS:
      the study sample comprised of 77 participants including 42 nulliparous women at
      least 32 weeks gestation or greater. It found significant difference in knowledge
      scores following training compared to baseline p=<0.0001 and at six months
      p=<0.0001 compared to immediate post training for both infant CPR and choking
      prevention. There was a 70% (n=58) response rate at six months with 84.5%
      reporting average or above confidence levels for performance of Infant CPR. The
      multiplier educational effect was 37.9% with 22 out of 58 participants sharing
      the kits with family and friends. Participants (57 out of 58) indicated that the
      maternity services should facilitate infant CPR training for expectant women and
      their partners. CONCLUSION: expectant women and their partners are very motivated
      to learn the skills of infant CPR. The facilitation of a 22 minute self
      instructional infant CPR kit is effective in increasing infant CPR knowledge and
      confidence in parents at six months post training. Findings provide the views of
      expectant and new parents on the relevance of acquiring the skills of infant CPR
      as part of their preparation for parenthood.

PMID- 25960110
TI  - 50 year trends in atrial fibrillation prevalence, incidence, risk factors, and
      mortality in the Framingham Heart Study: a cohort study.
AB  - BACKGROUND: Comprehensive long-term data on atrial fibrillation trends in men and
      women are scant. We aimed to provide such data through analysis of the Framingham
      cohort over 50 years. METHODS: We investigated trends in incidence, prevalence,
      and risk factors for atrial fibrillation and its association with stroke and
      mortality after onset in 9511 participants enrolled in the Framingham Heart Study
      between 1958 and 2007. We analysed trends within 10 year groups (1958-67, 1968
      77, 1978-87, 1988-97, and 1998-2007), stratified by sex. FINDINGS: During 50
      years of observation (202,417 person-years), 1544 cases of new-onset atrial
      fibrillation occurred (of whom 723 [47%] were women). Between 1958-67 and 1998
      2007, age-adjusted prevalence of atrial fibrillation quadrupled from 20.4 to 96.2
      cases per 1000 person-years in men and from 13.7 to 49.4 cases per 1000 person
      years in women; age-adjusted incidence increased from 3.7 to 13.4 new cases per
      1000 person-years in men and from 2.5 to 8.6 new cases per 1000 person-years in
      women (ptrend<0.0001 for all comparisons). For atrial fibrillation diagnosed by
      electrocardiograph (ECG) during routine Framingham examinations, age-adjusted
      prevalence per 1000 person-years increased (12.6 in 1958-67 to 25.7 in 1998-2007
      in men, ptrend=0.0007; 8.1 to 11.8 in women, ptrend=0.009). However, age-adjusted
      incidence of atrial fibrillation by Framingham Heart Study ECGs did not change
      significantly with time. Although the prevalence of most risk factors changed
      over time, their associated hazards for atrial fibrillation changed little.
      Multivariable-adjusted proportional hazards models revealed a 74% (95% CI 50-86%)
      decrease in stroke (hazards ratio [HR] 3.77, 95% CI 1.98-7.20 in 1958-1967
      compared with 1998-2007; ptrend=0.0001) and a 25% (95% CI -3-46%) decrease in
      mortality (HR 1.34, 95% CI 0.97-1.86 in 1958-1967 compared with 1998-2007;
      ptrend=0.003) in 20 years following atrial fibrillation onset. INTERPRETATION:
      Trends of increased incidence and prevalence of atrial fibrillation in the
      community were probably partly due to enhanced surveillance. Measures are needed
      to enhance early detection of atrial fibrillation, through increased awareness
      coupled with targeted screening programmes and risk factor-specific prevention.
      FUNDING: NIH, NHLBI, NINDS, Deutsche Forschungsgemeinschaft.

PMID- 25960114
TI  - Management of Advanced Heart Failure due to Cancer Therapy: the Present Role of
      Mechanical Circulatory Support and Cardiac Transplantation.
AB  - OPINION STATEMENT: Rapid improvement in antineoplastic therapy is increasing not
      only cancer survivorship but also the incidence of end-stage heart failure among
      breast and childhood cancer survivors. Anthracyclines and newer targeted
      therapies, including trastuzumab and tyrosine kinase inhibitors, are important
      agents implemented in clinical practice that carry cardiotoxic risk. While acute
      heart failure is often self-limited and reversible, delayed-onset heart failure
      significantly reduces survival. Extremes of age, renal dysfunction, pre-existing
      coronary artery disease, HER2 positivity, and multi-drug therapy are predictors
      of irreversible heart failure after chemotherapy. Left ventricular assist device
      (LVAD) implantation and cardiac transplantation can be performed safely in
      patients with end-stage heart failure (HF) from chemotherapy. However, co
      existing right ventricular dysfunction, hepatic congestion, and increased risk of
      bleeding make LVAD therapy challenging and dependent on careful patient
      selection. Cardiac transplantation in patients with chemotherapy-induced heart
      failure can be performed with good 10-year survival, but requires 5 years of
      cancer freedom and post-transplant infections remain a problem. Improvements in
      LVAD therapy and the expanding role of the total artificial heart and other
      durable biventricular support devices will likely provide more reliable surgical
      options for the management of end-stage HF after chemotherapy.

PMID- 25960115
TI  - Photoinduced Charge-Carrier Generation in Epitaxial MOF Thin Films: High
      Efficiency as a Result of an Indirect Electronic Band Gap?
AB  - For inorganic semiconductors crystalline order leads to a band structure which
      gives rise to drastic differences to the disordered material. An example is the
      presence of an indirect band gap. For organic semiconductors such effects are
      typically not considered, since the bands are normally flat, and the band-gap
      therefore is direct. Herein we show results from electronic structure
      calculations demonstrating that ordered arrays of porphyrins reveal a small
      dispersion of occupied and unoccupied bands leading to the formation of a small
      indirect band gap. We demonstrate herein that such ordered structures can be
      fabricated by liquid-phase epitaxy and that the corresponding crystalline organic
      semiconductors exhibit superior photophysical properties, including large charge
      carrier mobility and an unusually large charge-carrier generation efficiency. We
      have fabricated a prototype organic photovoltaic device based on this novel
      material exhibiting a remarkable efficiency. 

PMID- 25960116
TI  - Exercise, education, manual-therapy and taping compared to education for
      patellofemoral osteoarthritis: a blinded, randomised clinical trial.
AB  - OBJECTIVE: Patellofemoral joint osteoarthritis (PFJ OA) contributes considerably
      to knee OA symptoms. This study aimed to determine the efficacy of a PFJ-targeted
      exercise, education manual-therapy and taping program compared to OA education
      alone, in participants with PFJ OA. METHODS: A randomised, participant-blinded
      and assessor-blinded clinical trial was conducted in primary-care physiotherapy.
      92 people aged >=40 years with symptomatic and radiographic PFJ OA participated.
      Physiotherapists delivered the PFJ-targeted exercise, education, manual-therapy
      and taping program, or the OA-education (control condition) in eight sessions
      over 12 weeks. Primary outcomes at 3-month (primary) and 9-month follow-up: (1)
      patient-perceived global rating of change (2) pain visual analogue scale (VAS)
      (100 mm); and (3) activities of daily living (ADL) subscale of the Knee injury
      and Osteoarthritis Outcome Score (KOOS). RESULTS: 81 people (88%) completed the 3
      month follow-up and data analysed on an intention-to-treat basis. Between-group
      baseline similarity for participant characteristics was observed. The exercise,
      education, manual-therapy and taping program resulted in more people reporting
      much improvement (20/44) than the OA-education group (5/48) (number needed to
      treat 3 (95% confidence interval (CI) 2 to 5)) and greater pain reduction (mean
      difference: -15.2 mm, 95% CI -27.0 to -3.4). No significant effects on ADL were
      observed (5.8; 95% CI -0.6 to 12.1). At 9 months there were no significant
      effects for self-report of improvement, pain (-10.5 mm, 95% CI -22.7 to 1.8) or
      ADL (3.0, 95% CI -3.7 to 9.7). CONCLUSION: Exercise, education, manual-therapy
      and taping can be recommended to improve short-term patient rating of change and
      pain severity. However over 9-months, both options were equivalent. TRIAL
      REGISTRATION: Australian New Zealand Clinical Trials Registry
      (ACTRN12608000288325):
      https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=82878.

PMID- 25960117
TI  - The protective effect of meniscus allograft transplantation on articular
      cartilage: a systematic review of animal studies.
AB  - Despite widespread reporting on clinical results, the effect of meniscus
      allograft transplantation on the development of osteoarthritis is still unclear.
      The aim of this study was to systematically review all studies on the effect of
      meniscus allograft transplantation on articular cartilage in animals. Pubmed and
      Embase were searched for original articles concerning the effect of meniscus
      allograft transplantation on articular cartilage compared with both its positive
      (meniscectomy) and negative (either sham or non-operated) control in healthy
      animals. Outcome measures related to assessment of damage to articular cartilage
      were divided in five principal outcome categories. Standardized mean differences
      (SMD) were calculated and pooled to obtain an overall SMD and 95% confidence
      interval. 17 articles were identified, representing 14 original animal cohorts
      with an average timing of data collection of 24 weeks [range 4 weeks; 30 months].
      Compared to a negative control, meniscus allograft transplantation caused gross
      macroscopic (1.45 [0.95; 1.95]), histological (3.43 [2.25; 4.61]) damage to
      articular cartilage, and osteoarthritic changes on radiographs (3.12 [1.42;
      4.82]). Moreover, results on histomorphometrics and cartilage biomechanics are
      supportive of this detrimental effect on cartilage. On the other hand, meniscus
      allograft transplantation caused significantly less gross macroscopic (-1.19 [
      1.84; -0.54]) and histological (-1.70 [-2.67; -0.74]) damage to articular
      cartilage when compared to meniscectomy. However, there was no difference in
      osteoarthritic changes on plain radiographs (0.04 [-0.48; 0.57]), and results on
      histomorphometrics and biomechanics did neither show a difference in effect
      between meniscus allograft transplantation and meniscectomy. In conclusion,
      although meniscus allograft transplantation does not protect articular cartilage
      from damage, it reduces the extent of it when compared with meniscectomy. 

PMID- 25960118
TI  - Clinical perspectives on the rationale for potassium supplementation.
AB  - Hypokalemia is a common electrolyte disturbance, observed in > 20% of
      hospitalized patients. Hypokalemia, although not formally defined, is generally
      considered to be when serum potassium levels fall below the normal value of 3.6
      mmol/L. In contrast to other electrolytes, potassium is primarily an
      intracellular ion: only 2% of all potassium in the body is present in the
      extracellular fluid, so a small decrease in serum potassium may represent a
      significant decrease in intracellular potassium. Individuals with mildly
      decreased potassium levels (3.0-3.5 mmol/L) may be asymptomatic, but patients
      with more pronounced decreases may report symptoms including muscle weakness,
      fatigue, and constipation. Very low serum potassium levels (<= 2.5 mmol/L) can
      lead to muscle necrosis, paralysis, cardiac arrhythmias, and impaired
      respiration, which can be life-threatening. Absent comprehensive and robust
      treatment guidelines, strategies for the prevention or treatment of hypokalemia,
      such as how to diagnose hypokalemia, when to treat patients, what dosage regimen
      of potassium supplementation to use and for how long, are often based on the
      experience of the physician and empirical evidence. However, proper evaluation
      and treatment of hypokalemia in patients is essential because of associated
      morbidities. Because small potassium deficits in serum represent large body
      losses, potassium repletion requires substantial and prolonged supplementation.
      For patients with known risk factors for hypokalemia (e.g. hypertension, heart
      failure, or diabetes), careful monitoring is crucial to avoid the adverse
      sequelae associated with potassium deficits and to ensure that adequate and
      timely preventive measures can be taken. In this review, we provide practical
      insights into the etiology, differential diagnosis, and treatment of hypokalemia,
      including treatment strategies for patients with known risk factors. 

PMID- 25960119
TI  - Number of ovulations in culled Landrace * Yorkshire gilts in the tropics
      associated with age, body weight and growth rate.
AB  - The objective of the present study was to determine the number of ovulations in
      culled Landrace * Yorkshire (LY) crossbred gilts in the tropics associated with
      age, body weight and growth rate. The genital organs from 316 gilts were examined
      for gross abnormalities, and those with normal cyclic ovaries (n=155, 307 +/- 4.1
      days of age, 148 +/- 1.6 kg body weight) were included in the analyses. Number of
      ovulations was defined by a count of the corpora lutea (CL) from both ovaries. On
      average, the number of ovulations in LY gilts was 15.9 +/- 0.3 (range 4 to 27).
      The number of ovulations correlated with the body weight (r=0.31, P<0.001) and
      growth rate (r=0.20, P=0.015) of the gilts, but not with their age (P>0.05).
      Gilts with a body weight of 141 to 150 kg (17.0 CL, n=31) ovulated more than
      those with a body weight <=130 kg (14.1 CL, P=0.014, n=23). In conclusion, both
      the body weight and growth rate of the gilts were significantly correlated with
      the number of ovulations. The maximum number of ovulations was found in gilts at
      a body weight of above 141 kg.

PMID- 25960120
TI  - A comparison of the immunological effects of propofol and isoflurane for
      maintenance of anesthesia in healthy dogs.
AB  - Most anesthetics have an immuno-suppressive effect on cellular and neurohumoral
      immunity, and research shows that total intravenous anesthesia (TIVA) with
      propofol has a greater immuno-protective effect than inhalational anesthesia in
      human medicine. However, in veterinary clinics, these effects remain ambiguous.
      To clarify the details, we focused on propofol and isoflurane, investigating
      clinical blood hematology and immunological profiles drawn from healthy dogs
      under and after two anesthesia techniques. Twelve healthy adult beagles were
      included in this study, randomly assigned to the propofol anesthesia group (group
      P: n=6) or the isoflurane anesthesia group (group I: n=6). In both groups, the
      number of lymphocytes in peripheral blood decreased after 2 hr of anesthesia (2
      hr), but group P showed significantly less decrease than group I. For T
      lymphocyte subsets examined by flowcytometry, the ratio of CD3+, CD4+ and CD8+
      lymphocytes in the peripheral blood mononuclear cell (PBMC) of group P at 2 hr
      also exhibited a high level compared to group I. Moreover, for mRNA expression of
      cytokines measured by real-time PCR, the IL2 (pro-inflammatory cytokine) of group
      P showed no decrease like group I. The IL10 (anti-inflammatory cytokine) of group
      P also showed no increase like group I, while both cytokines maintained nearly
      the same level until 2 hr. These results suggest that, compared to propofol,
      isoflurane had more strongly immuno-suppression caused by anesthesia, and
      propofol itself might have some immuno-protective effects. Thus, TIVA with
      propofol might benefit immunological support in the perioperative period of dogs.

PMID- 25960122
TI  - Ubiquity of Kelvin-Helmholtz waves at Earth's magnetopause.
AB  - Magnetic reconnection is believed to be the dominant process by which solar wind
      plasma enters the magnetosphere. However, for periods of northward interplanetary
      magnetic field (IMF) reconnection is less likely at the dayside magnetopause, and
      Kelvin-Helmholtz waves (KHWs) may be important agents for plasma entry and for
      the excitation of ultra-low-frequency (ULF) waves. The relative importance of
      KHWs is controversial because no statistical data on their occurrence frequency
      exist. Here we survey 7 years of in situ data from the NASA THEMIS (Time History
      of Events and Macro scale Interactions during Substorms) mission and find that
      KHWs occur at the magnetopause ~19% of the time. The rate increases with solar
      wind speed, Alfven Mach number and number density, but is mostly independent of
      IMF magnitude. KHWs may thus be more important for plasma transport across the
      magnetopause than previously thought, and frequently drive magnetospheric ULF
      waves. 

PMID- 25960121
TI  - Gastrointestinal basidiobolomycosis in a dog.
AB  - An 8-year-old, spayed, female Shiba dog was presented to a referring veterinarian
      with a complaint of chronic diarrhea and anorexia. Ultrasound and radiographs
      revealed an irregular mass in the pelvic cavity. The mass and the affected
      section of colon were surgically removed. Histopathological examination revealed
      multifocal coalescing granulomas and effaced intestinal structures. Central
      necrotic debris surrounded by multinucleated giant cells, lymphocytes, plasma
      cells and neutrophils was observed. Numerous, irregularly branched hyphae with
      pale basophilic, thin walls and occasional bulbous enlargements at the tips were
      present. Polymerase chain reaction identified Basidiobolus ranarum, successfully
      confirming a definitive diagnosis of basidiobolomycosis. To the best of our
      knowledge, this is the first report of intestinal basidiobolomycosis in a dog. 

PMID- 25960123
TI  - Characterization of genome-wide ordered sequence-tagged Mycobacterium mutant
      libraries by Cartesian Pooling-Coordinate Sequencing.
AB  - Reverse genetics research approaches require the availability of methods to
      rapidly generate specific mutants. Alternatively, where these methods are
      lacking, the construction of pre-characterized libraries of mutants can be
      extremely valuable. However, this can be complex, expensive and time consuming.
      Here, we describe a robust, easy to implement parallel sequencing-based method
      (Cartesian Pooling-Coordinate Sequencing or CP-CSeq) that reports both on the
      identity as well as on the location of sequence-tagged biological entities in
      well-plate archived clone collections. We demonstrate this approach using a
      transposon insertion mutant library of the Mycobacterium bovis BCG vaccine
      strain, providing the largest resource of mutants in any strain of the M.
      tuberculosis complex. The method is applicable to any entity for which sequence
      tagged identification is possible. 

PMID- 25960124
TI  - Nocardia pyomyositis in a patient with granulomatosis with polyangiitis.

PMID- 25960125
TI  - Synthesis and anti-neuroinflammatory activity of lactone benzoyl hydrazine and 2
      nitro-1-phenyl-1h-indole derivatives as p38alpha MAPK inhibitors.
AB  - Inhibition of p38 mitogen-activated protein kinases (MAPKs) would allow
      significant modulation of the neuroinflammation condition associated with
      Alzheimer's disease (AD). Inspired from the pharmacophore of natural NF-kappaB
      and p38alpha MAPK inhibitor 5,6-dehydrokawain and p38alpha MAPK inhibitors 1a, 1
      pyrazolyl-3-(4-((2-anilinopyrimidin-4-yl)oxy)napththalen-1-yl)ureas, and 1b, a
      class of indole-pyrimidinyl compounds which were patented respectively, we
      designed, de novo synthesized, and evaluated two kinds of novel series of lactone
      benzoyl hydrazine derivatives and 2-nitro-1-phenyl-1H-indole derivatives in an
      effort to develop pharmacologically tractable agents to alleviate the progression
      of AD. Fourteen of the seventeen synthesized compounds exhibit significant
      inhibitory effect on the nitric oxide (NO) production induced by
      lipopolysaccharide (LPS)-induced microglia activation with IC50 less than the
      control 5,6-dehydrokawain. Notably, compound 27, 6-methoxy-2-nitro-1-(1H-1, 2, 3
      triazol-1-yl)-1H-indole, with IC50 values of 1.6 MUm can markedly inhibit
      p38alpha MAPK and NO release in BV-2 microglial cells. The molecular dynamic (MD)
      simulations demonstrate that compound 27 inhibits p38alpha MAPK through binding
      to the Glu71 and Asp168 residues. Moreover, in vitro study shows that all
      compounds can easily cross the blood-brain barrier (BBB) and did not exhibit any
      acute cellular toxicity checked by MTT assay. These investigations provide
      promising chemical lead candidate as anti-neuroinflammatory agents for AD. 

PMID- 25960126
TI  - Prevention of hospital-acquired hyponatraemia: individualised fluid therapy.
AB  - BACKGROUND: Large amounts of fluids are daily prescribed to hospitalised patients
      across different medical specialities. Unfortunately, inappropriate fluid
      administration commonly causes iatrogenic hyponatraemia with associated increase
      in morbidity and mortality. METHODS/RESULTS: Fundamental for prevention of
      hospital-acquired hyponatraemia is an understanding of what determines plasma
      sodium concentration (P-[Na(+) ]) in the individual patient. P-[Na(+) ] is
      determined by balances of water and cations according to Edelman. This paper
      discusses the mechanisms influencing water and cation balances. In the
      hospitalised patient, non-osmotic antidiuretic hormone secretion is frequent and
      results in a reduced renal electrolyte-free water clearance (EFWC). This
      condition puts the patient at risk of hyponatraemia upon infusion of fluids that
      are hypotonic such as 5% glucose, Darrow-glucose, NaKglucose and 0.45% NaCl in 5%
      glucose. It is suggested that individualised fluid therapy includes the
      following: Firstly, bolus therapy with Ringer-acetate/Ringer-lactate/0.9% NaCl in
      the hypovolaemic patient to minimise the risk of fluid under-/overload. Secondly,
      P-[Na(+) ] should be monitored together with the balances influencing P-[Na(+) ].
      This may include EFWC in patients at additional risk of hyponatraemia. In
      patients with potentially reduced intracranial compliance (e.g. meningitis,
      intracranial bleeding, cerebral contusion and brain oedema), even a small
      decrease in P-[Na(+) ] induced by slightly hypotonic fluids like Ringer
      acetate/Ringer-lactate can increase the intracranial pressure dramatically.
      Consequently, 0.9 % NaCl is recommended as first-line fluid for such patients.
      CONCLUSIONS: The occurrence of hospital-acquired hyponatraemia may be reduced by
      prescribing fluids, type and amount, with the same dedication as shown for other
      drugs.

PMID- 25960128
TI  - Predictors of preoperative MRI for breast cancer: differences by data source.
AB  - AIM: Investigate how the results of predictive models of preoperative MRI for
      breast cancer change based on available data. MATERIALS & METHODS: A total of
      1919 insured women aged >=18 with stage 0-III breast cancer diagnosed 2002-2009.
      Four models were compared using nested multivariable logistic, backwards stepwise
      regression; model fit was assessed via area under the curve (AUC), R2. RESULTS:
      MRI recipients (n = 245) were more recently diagnosed, younger, less comorbid,
      with higher stage disease. Significant variables included: Model 1/Claims (AUC =
      0.76, R2 = 0.10): year, age, location, income; Model 2/Cancer Registry (AUC =
      0.78, R2 = 0.12): stage, breast density, imaging indication; Model 3/Medical
      Record (AUC = 0.80, R2 = 0.13): radiologic recommendations; Model 4/Risk Factor
      Survey (AUC = 0.81, R2 = 0.14): procedure count. CONCLUSION: Clinical variables
      accounted for little of the observed variability compared with claims data.

PMID- 25960129
TI  - Insecticidal efficacy and persistence of a co-occluded binary mixture of
      Helicoverpa armigera nucleopolyhedrovirus (HearNPV) variants in protected and
      field-grown tomato crops on the Iberian Peninsula.
AB  - BACKGROUND: A binary co-occluded mixture (HearSP1B:LB6) of Helicoverpa armigera
      single nucleopolyhedrovirus (HearNPV) variants was previously found to be highly
      pathogenic under laboratory conditions. The insecticidal efficacy and persistence
      of this mixture were determined in greenhouse and field-grown tomato crops in
      Spain and Portugal. RESULTS: Concentrations of 10(9) -10(11) occlusion bodies
      (OBs) L(-1) of HearSP1B:LB6 resulted in 89-100% mortality of larvae on treated
      tomato plants in growth chambers. In protected tomato crops, application of
      10(10) OBs L(-1) of HearSP1B:LB6 was as effective as Bacillus thuringiensis (Bt)
      and spinosad in reducing the percentage of damaged fruits, and resulted in higher
      larval mortality than the Bt treatment. In open-field tomato crops, virus
      treatments were as effective in reducing the percentage of damaged fruit as
      spinosad, Bt and chlorpyrifos treatments. The persistence of the insecticides on
      tomato plants was negatively correlated with solar radiation in both field and
      greenhouse settings. Residual insecticidal activity of OBs on protected tomato
      crops at 6 days post-application was 55 and 35% higher than that of Bt and
      spinosad respectively. On field-grown tomato, OB persistence was significantly
      lower than with spinosad or chlorpyrifos. CONCLUSION: The efficacy and
      persistence of HearSP1B:LB6 OBs were comparable with those of commercial
      insecticides in both field and greenhouse tomato crops. Future studies should
      focus on reducing application rates to determine insecticidal efficacy at lower
      OB concentrations. (c) 2015 Society of Chemical Industry.

PMID- 25960130
TI  - Why close relatives make bad neighbours: phylogenetic conservatism in niche
      preferences and dispersal disproves Darwin's naturalization hypothesis in the
      thistle tribe.
AB  - The number of exotic plant species that have been introduced into the United
      States far exceeds that of other groups of organisms, and many of these have
      become invasive. As in many regions of the globe, invasive members of the thistle
      tribe, Cardueae, are highly problematic in the California Floristic Province, an
      established biodiversity hotspot. While Darwin's naturalization hypothesis posits
      that plant invaders closely related to native species would be at a disadvantage,
      evidence has been found that introduced thistles more closely related to native
      species are more likely to become invasive. To elucidate the mechanisms behind
      this pattern, we modelled the ecological niches of thistle species present in the
      province and compared niche similarity between taxa and their evolutionary
      relatedness, using fossil-calibrated molecular phylogenies of the tribe. The
      predicted niches of invasive species were found to have higher degrees of overlap
      with native species than noninvasive introduced species do, and pairwise niche
      distance was significantly correlated with phylogenetic distance, suggesting
      phylogenetic niche conservatism. Invasive thistles also displayed superior
      dispersal capabilities compared to noninvasive introduced species, and these
      capabilities exhibited a phylogenetic signal. By analysing the modelled
      ecological niches and dispersal capabilities of over a hundred thistle species,
      we demonstrate that exapted preferences to the invaded environment may explain
      why close exotic relatives may make bad neighbours in the thistle tribe. 

PMID- 25960127
TI  - Engineered biosynthesis of natural products in heterologous hosts.
AB  - Natural products produced by microorganisms and plants are a major resource of
      antibacterial and anticancer drugs as well as industrially useful compounds.
      However, the native producers often suffer from low productivity and titers. Here
      we summarize the recent applications of heterologous biosynthesis for the
      production of several important classes of natural products such as terpenoids,
      flavonoids, alkaloids, and polyketides. In addition, we will discuss the new
      tools and strategies at multi-scale levels including gene, pathway, genome and
      community levels for highly efficient heterologous biosynthesis of natural
      products. 

PMID- 25960131
TI  - Sp1 transcription factor: A long-standing target in cancer chemotherapy.
AB  - Sp1 (specificity protein 1) is a well-known member of a family of transcription
      factors that also includes Sp2, Sp3 and Sp4, which are implicated in an ample
      variety of essential biological processes and have been proven important in cell
      growth, differentiation, apoptosis and carcinogenesis. Sp1 activates the
      transcription of many cellular genes that contain putative CG-rich Sp-binding
      sites in their promoters. Sp1 and Sp3 proteins bind to similar, if not the same,
      DNA tracts and compete for binding, thus they can enhance or repress gene
      expression. Evidences exist that the Sp-family of proteins regulates the
      expression of genes that play pivotal roles in cell proliferation and metastasis
      of various tumors. In patients with a variety of cancers, high levels of Sp1
      protein are considered a negative prognostic factor. A plethora of compounds can
      interfere with the trans-activating activities of Sp1 and other Sp proteins on
      gene expression. Several pathways are involved in the down-regulation of Sp
      proteins by compounds with different mechanisms of action, which include not only
      the direct interference with the binding of Sp proteins to their putative DNA
      binding sites, but also promoting the degradation of Sp protein factors. Down
      regulation of Sp transcription factors and Sp1-regulated genes is drug-dependent
      and it is determined by the cell context. The acknowledgment that several of
      those compounds are safe enough might accelerate their introduction into clinical
      usage in patients with tumors that over-express Sp1. 

PMID- 25960132
TI  - Promoting blood circulation for removing blood stasis therapy for acute
      intracerebral hemorrhage: a systematic review and meta-analysis.
AB  - AIM: To conduct a systematic review and meta-analysis to assess the current
      evidence available regarding the promoting blood circulation and removing blood
      stasis (PBCRBS) therapy for Chinese patients with acute intracerebral hemorrhage
      (ICH). METHODS: Six databases were searched from their inception to November
      2013. The studies assessed in >= 4 domains with 'yes' were selected for detailed
      assessment and meta-analysis. The herbal compositions for PBCRBS therapy for
      acute ICH patients were also assessed. RESULTS: From the 6 databases, 292 studies
      claimed randomized-controlled clinical trials (RCTs). Nine studies with 798
      individuals were assessed in >= 4 domains with 'yes' by using the Cochrane RoB
      tool. Meta-analysis showed that PBCRBS monotherapy and adjuvant therapy for acute
      ICH could improve the neurological function deficit, reduce the volume of
      hematoma and perihematomal edema, and lower the mortality rate and dependency.
      Moreover, there were fewer adverse effects when compared with Western
      conventional medication controls. Xueshuantong Injection and Fufang Danshen
      Injection, Buyang Huanwu Decoction and Liangxue Tongyu formula, and three herbs
      (danshen root, sanqi and leech) were the most commonly used Chinese herbal patent
      injections, herbal prescriptions and single herbs, respectively. CONCLUSION:
      Despite the apparently positive findings, it is premature to conclude that there
      is sufficient efficacy and safety of PBCRBS for ICH because of the high clinical
      heterogeneity of the included studies and small number of trials in the meta
      analysis. Further large sample-sizes and rigorously designed RCTs are needed.

PMID- 25960133
TI  - Deciphering the therapeutic mechanisms of Xiao-Ke-An in treatment of type 2
      diabetes in mice by a Fangjiomics approach.
AB  - AIM: Xiao-Ke-An (XKA) is a traditional Chinese medicine (TCM) formula for the
      treatment of type 2 diabetes (T2D), and the effective ingredients and their
      targets as well as the mechanisms of XKA remain to be elucidated. In this study
      we investigated the therapeutic mechanisms of XKA in the treatment of T2D in mice
      using a Fangjiomics approach. METHODS: KKAy mice feeding on a high-fat diet were
      used as models of T2D, and were orally treated with XKA (0.75 or 1.5 g . kg(-1) .
      d(-1)) for 32 d. Microarray mRNA expression data were obtained from the livers of
      the mice. Differentially expressed genes (DEGs) were identified by reverse rate
      analysis and ANOVA analysis. The compounds in XKA were identified by LC-MS
      analysis or collected from TCM databases. The relationships between the compounds
      and targets were established by combining the DEGs with information derived from
      mining literature or herb target databases. Relevant pathways were identified
      through a Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis
      using WebGestalt. RESULTS: The compound-target-pathway network based on compounds
      identified by LC-MS analysis (NCA) included 20 constituent compounds, 46 targets
      and 36 T2D-related pathways, whereas the compound-target-pathway network based on
      compounds collected from databases (NCD) consisted of 40 compounds, 68 targets
      and 21 pathways. In the treatment of T2D, XKA might act mainly by improving
      carbohydrate and lipid metabolism, as well as ameliorating insulin resistance,
      inflammation and diabetic vascular complications. CONCLUSION: The network-based
      approach reveals complex therapeutic mechanisms of XKA in the treatment of T2D in
      mice that involve numerous compounds, targets, and signaling pathways.

PMID- 25960136
TI  - High proton conduction in a new alkali metal-templated open-framework
      aluminophosphate.
AB  - A new open-framework aluminophosphate Na6[(AlPO4)8(OH)6].8H2O (JU103) has been
      synthesized by utilization of the organotemplate-free synthetic route in alkali
      metal-containing system. The as-prepared JU103 possesses two-dimensional
      intersecting 8-ring channels. Sodium ions and water molecules in the channels
      facilitates JU103 excellent proton conductivity up to 3.59 * 10(-3) S cm(-1) (293
      K, 98% RH). 

PMID- 25960134
TI  - Phenotype-dependent alteration of pathways and networks reveals a pure
      synergistic mechanism for compounds treating mouse cerebral ischemia.
AB  - AIM: Our previous studies have showed that ursodeoxycholic acid (UA) and
      jasminoidin (JA) effectively reduce cerebral infarct volume in mice. In this
      study we explored the pure synergistic mechanism of these compounds in treatment
      of mouse cerebral ischemia, which was defined as synergistic actions specific for
      phenotype variations after excluding interference from ineffective compounds.
      METHODS: Mice with focal cerebral ischemia were treated with UA, JA or a
      combination JA and UA (JU). Concha margaritifera (CM) was taken as ineffective
      compound. Cerebral infarct volume of the mice was determined, and the hippocampi
      were taken for microarray analysis. Particular signaling pathways and biological
      functions were enriched based on differentially expressed genes, and
      corresponding networks were constructed through Ingenuity Pathway Analysis.
      RESULTS: In phenotype analysis, UA, JA, and JU significantly reduced the ischemic
      infarct volume with JU being superior to UA or JA alone, while CM was
      ineffective. As a result, 4 pathways enriched in CM were excluded. Core pathways
      in the phenotype-positive groups (UA or JA) were involved in neuronal homeostasis
      and neuropathology. JU-contributing pathways included all UA-contributing and the
      majority (71.7%) of JA-contributing pathways, and 10 new core pathways whose
      effects included inflammatory immunity, apoptosis and nervous system development.
      The functions of JU group included all functions of JA group, the majority
      (93.1%) of UA-contributing functions, and 3 new core functions, which focused on
      physiological system development and function. CONCLUSION: The pure synergism
      between UA and JA underlies 10 new core pathways and 3 new core functions, which
      are involved in inflammation, immune responses, apoptosis and nervous system
      development.

PMID- 25960135
TI  - Herbal prescription Chang'an II repairs intestinal mucosal barrier in rats with
      post-inflammation irritable bowel syndrome.
AB  - AIM: The herbal prescription Chang'an II is derived from a classical TCM formula
      Tong-Xie-Yao-Fang for the treatment of liver-qi stagnation and spleen deficiency
      syndrome of irritable bowel syndrome (IBS). In this study we investigated the
      effects of Chang'an II on the intestinal mucosal immune barrier in a rat post
      inflammation IBS (PI-IBS) model. METHODS: A rat model of PI-IBS was established
      using a multi-stimulation paradigm including early postnatal sibling deprivation,
      bondage and intrarectal administration of TNBS. Four weeks after TNBS
      administration, the rats were treated with Chang'an II (2.85, 5.71 and 11.42 g .
      kg(-1) . d(-1), ig) for 14 d. Intestinal sensitivity was assessed based on the
      abdominal withdrawal reflex (AWR) scores and fecal water content. Open field test
      and two-bottle sucrose intake test were used to evaluate the behavioral changes.
      CD4(+) and CD8(+) cells were counted and IL-1beta and IL-4 levels were measured
      in intestinal mucosa. Transmission electron microscopy was used to evaluate
      ultrastructural changes of the intestinal mucosal barrier. RESULTS: PI-IBS model
      rats showed significantly increased AWR reactivity and fecal water content, and
      decreased locomotor activity and sucrose intake. Chang'an II treatment not only
      reduced AWR reactivity and fecal water content, but also suppressed the anxiety
      and depressive behaviors. Ultrastructural study revealed that the gut mucosal
      barrier function was severely damaged in PI-IBS model rats, whereas Chang'an II
      treatment relieved intestinal mucosal inflammation and repaired the gut mucosal
      barrier. Furthermore, PI-IBS model rats showed a significantly reduced
      CD4(+)/CD8(+) cell ratio in lamina propria and submucosa, and increased IL-1beta
      and reduced IL-4 expression in intestinal mucosa, whereas Chang'an II treatment
      reversed PI-IBS-induced changes in CD4(+)/CD8(+) cell ratio and expression of IL
      1beta and IL-4. CONCLUSION: Chang'an II treatment protects the intestinal mucosa
      against PI-IBS through anti-inflammatory, immunomodulatory and anti-anxiety
      effects.

PMID- 25960139
TI  - Purification, Partial Characterizations, and N-Terminal Amino Acid Sequence of a
      Procoagulant Protein FV-2 from Daboia Russelli Siamensis (Myanmar) Venom.
AB  - In this study, we purified and characterized the procoagulant protein FV-2 from
      Daboia russelli siamensis (Myanmar) venom using ion-exchange chromatography on CM
      Sephadex C-50 and gel filtration on SuperdexTM G-75 column. The activation of
      factor X and prothrombin was determined, respectively, by specific chromogenic
      substrates. The fibrinogen-clotting activity, thermal stability, and pH stability
      were also determined. The N-treminal sequence was determined by the National
      Center of Biomedical Analysis of China. In the end, FV-2 was achieved with a
      molecular weight of 13,608.0 Da. It could activate factor X, but did not affect
      prothrombin or fibrinogen. The suitable pH was 6.5-7.5, and the suitable
      temperature ranged from 25 to 60 degrees C. The N-terminal sequence was Asn-Phe
      Phe-Gln-Phe-Ala-Glu-Met-Ile-Val-Lys-Met-Thr-Gly-Lys. Taken together, our studies
      suggest that FV-2 is a factor X-activating enzyme, which can activate factor X to
      factor Xa, but it has no effect on prothrombin and fibrinogen.

PMID- 25960138
TI  - Remuneration of medical specialists. Drivers of the differences between six
      European countries.
AB  - Between countries there are large differences in the remuneration of medical
      specialists. We compared the remuneration levels in 2010 in six countries:
      Belgium, Denmark, England, France, Germany and the Netherlands. We used OECD
      figures for the remuneration levels, but corrected them extensively for
      differences in measurement between countries. English doctors earned most in
      2010, French doctors earned least. For the six countries under study the number
      of doctors per capita is most consistent with the differences in income.
      Surprisingly, the payment scheme (salaried or fee-for-service) does not seem to
      account for differences between countries, although within countries fee-for
      service specialists earn more than their salaried counterparts. Differences in
      the role of the GP, differences in workload, composition of the workforce and
      education could not account for differences in remuneration between these six
      countries. As our conclusions are based on only six countries more research
      involving a larger number of countries is needed to confirm these findings. 

PMID- 25960137
TI  - Surname-inferred Andean ancestry is associated with child stature and limb
      lengths at high altitude in Peru, but not at sea level.
AB  - OBJECTIVES: Native Andean ancestry gives partial protection from reduced
      birthweight at high altitude in the Andes compared with European ancestry.
      Whether Andean ancestry is also associated with body proportions and greater
      postnatal body size at altitude is unknown. Therefore, we tested whether a
      greater proportion of Andean ancestry is associated with stature and body
      proportions among Peruvian children at high and low altitude. METHODS: Height,
      head circumference, head-trunk height, upper and lower limb lengths, and tibia,
      ulna, hand and foot lengths, were measured in 133 highland and 169 lowland
      children aged 6 months to 8.5 years. For highland and lowland groups separately,
      age-sex-adjusted anthropometry z scores were regressed on the number of
      indigenous parental surnames as a proxy for Andean ancestry, adjusting for
      potential confounders (maternal age and education, parity, altitude [highlands
      only]). RESULTS: Among highland children, greater Andean ancestry was negatively
      associated with stature and tibia, ulna, and lower limb lengths, independent of
      negative associations with greater altitude for these measurements. Relationships
      were strongest for tibia length: each additional Andean surname or 1,000 m
      increase at altitude among highland children was associated with 0.18 and 0.65 z
      score decreases in tibia length, respectively. Anthropometry was not
      significantly associated with ancestry among lowland children. CONCLUSIONS:
      Greater Andean ancestry is associated with shorter stature and limb measurements
      at high but not low altitude. Gene-environment interactions between high altitude
      and Andean ancestry may exacerbate the trade-off between chest dimensions and
      stature that was proposed previously, though we could not test this directly.

PMID- 25960141
TI  - The importance of preoperative diagnosis of blister aneurysms.
AB  - We describe a series of 14 surgical blister aneurysm (BA) patients and compare
      outcomes in those with known cerebral BA to those lacking preoperative BA
      diagnosis/recognition. BA are broad, fragile, pathologic dilatations of the
      intracranial arteries. They have a low prevalence but are associated with
      substantially higher surgical morbidity and mortality rates than saccular
      aneurysms. A confirmed, preoperative BA diagnosis can alter operative management
      and technique. We performed a retrospective review of prospectively collected
      data on aneurysm patients undergoing surgery at a major academic institution. All
      patients from 1990 to 2011 with a postoperative BA diagnosis were included. Chart
      reviews were performed to identify patients with preoperative BA diagnoses and
      collect descriptive data. We identified 14 patients, 12 of whom presented with
      subarachnoid hemorrhage. The age of the cohort (mean +/- standard deviation: 41.8
      +/- 13.9 years) was lower than that generally reported for saccular aneurysm
      populations. Preoperatively diagnosed BA had an intraoperative rupture (IOR) rate
      of 28.6% (2/7) compared to a 57.1% (4/7) rate in the undiagnosed patients. The
      mortality rate in the preoperatively diagnosed cohort was 14.3% (1/7) while that
      of the undiagnosed group was 42.8% (3/7). BA remain a diagnostic and treatment
      challenge with morbidity and mortality rates exceeding those of saccular
      aneurysms. Preoperative BA diagnosis may decrease IOR and mortality rates and
      improve patient outcomes.

PMID- 25960142
TI  - In vitro MRI of biodegradable hybrid (iron oxide/polycaprolactone) magnetic
      nanoparticles prepared via modified double emulsion evaporation mechanism.
AB  - Hybrid magnetic particles are being applied in biomedical field for various aims.
      One of such aim is use of magnetic particles for diagnostic purposes especially
      in imaging mechanisms. In vitro magnetic resonance imaging of biodegradable
      hybrid (iron oxide/polycaprolactone) magnetic nanoparticles is carried out.
      Hybrid magnetic nanoparticles were prepared by encapsulation of iron oxide
      nanoparticles (IONPs) in polycaprolactone (PCL) via modified double emulsion
      evaporation technique. Both the IONPs and hybrid nanoparticles were characterized
      for their sizes, zeta potential, microscopic, thermogravimetric, and magnetism.
      Prepared particles were investigated for T1 and T2 weighted enhancement of
      contrast in vitro in water. A comparison of the prepared particles was done with
      commercially available Gadolinium for the contrast efficiency in MRI. Results
      showed the prepared particles exhibited nanosize range, good morphology and
      superparamagnetic character. The enhancement in the MRI contrast of the prepared
      particles was observed and found to depend on type of the prepared particles.
      Comparison of the MRI contrast of the prepared particles with the commercial
      Gadolinium suggests their usefulness as T2 contrast agent. 

PMID- 25960140
TI  - Differential effects of cocaine exposure on the abundance of phospholipid species
      in rat brain and blood.
AB  - BACKGROUND: Lipid profiles in the blood are altered in human cocaine users,
      suggesting that cocaine exposure can induce lipid remodeling. METHODS: Lipid
      changes in the brain tissues of rats sensitized to cocaine were determined
      through shotgun lipidomics using electrospray ionization-mass spectrometry (ESI
      MS). We also performed pairwise principal component analysis (PCA) to assess
      cocaine-induced changes in blood lipid profiles. Alterations in the abundance of
      phospholipid species were correlated with behavioral changes in the magnitude of
      either the initial response to the drug or locomotor sensitization. RESULTS:
      Behavioral sensitization altered the relative abundance of several phospholipid
      species in the hippocampus and cerebellum, measured one week following the final
      exposure to cocaine. In contrast, relatively few effects on phospholipids in
      either the dorsal or the ventral striatum were observed. PCA analysis
      demonstrated that cocaine altered the relative abundance of several
      glycerophospholipid species as compared to saline-injected controls in blood.
      Subsequent MS/MS analysis identified some of these lipids as
      phosphatidylethanolamines, phosphatidylserines and phosphatidylcholines. The
      relative abundance of some of these phospholipid species were well-correlated
      (R(2) of 0.7 or higher) with either the initial response to cocaine or locomotor
      sensitization. CONCLUSION: Taken together, these data demonstrate that a cocaine
      induced sensitization assay results in the remodeling of specific phospholipids
      in rat brain tissue in a region-specific manner and also alters the intensities
      of certain types of phospholipid species in rat blood. These results further
      suggest that such changes may serve as biomarkers to assess the neuroadaptations
      occurring following repeated exposure to cocaine.

PMID- 25960143
TI  - Meralgia paresthetica caused by a pancreatic pseudocyst.

PMID- 25960144
TI  - Targets of drugs are generally, and targets of drugs having side effects are
      specifically good spreaders of human interactome perturbations.
AB  - Network-based methods are playing an increasingly important role in drug design.
      Our main question in this paper was whether the efficiency of drug target
      proteins to spread perturbations in the human interactome is larger if the
      binding drugs have side effects, as compared to those which have no reported side
      effects. Our results showed that in general, drug targets were better spreaders
      of perturbations than non-target proteins, and in particular, targets of drugs
      with side effects were also better spreaders of perturbations than targets of
      drugs having no reported side effects in human protein-protein interaction
      networks. Colorectal cancer-related proteins were good spreaders and had a high
      centrality, while type 2 diabetes-related proteins showed an average spreading
      efficiency and had an average centrality in the human interactome. Moreover, the
      interactome-distance between drug targets and disease-related proteins was higher
      in diabetes than in colorectal cancer. Our results may help a better
      understanding of the network position and dynamics of drug targets and disease
      related proteins, and may contribute to develop additional, network-based tests
      to increase the potential safety of drug candidates. 

PMID- 25960145
TI  - RYR1-related myopathies: a wide spectrum of phenotypes throughout life.
AB  - BACKGROUND AND PURPOSE: Although several recent studies have implicated RYR1
      mutations as a common cause of various myopathies and the malignant hyperthermia
      susceptibility (MHS) trait, many of these studies have been limited to certain
      age groups, confined geographical regions or specific conditions. The aim of the
      present study was to investigate the full spectrum of RYR1-related disorders
      throughout life and to use this knowledge to increase vigilance concerning
      malignant hyperthermia. METHODS: A retrospective cohort study was performed on
      the clinical, genetic and histopathological features of all paediatric and adult
      patients in whom an RYR1 mutation was detected in a national referral centre for
      both malignant hyperthermia and inherited myopathies (2008-2012). RESULTS: The
      cohort of 77 non-related patients (detection rate 28%) included both congenital
      myopathies with permanent weakness and 'induced' myopathies such as MHS and non
      anaesthesia-related episodes of rhabdomyolysis or hyperCKemia, manifested
      throughout life and triggered by various stimuli. Sixty-one different mutations
      were detected, of which 24 were novel. Some mutations are present in both
      dominant (MHS) and recessive modes (congenital myopathy) of inheritance, even
      within families. Histopathological features included an equally wide spectrum,
      ranging from only subtle abnormalities to prominent cores. CONCLUSIONS: This
      broad range of RYR1-related disorders often presents to the general paediatric
      and adult neurologist. Its recognition is essential for genetic counselling and
      improving patients' safety during anaesthesia. Future research should focus on in
      vitro testing by the in vitro contracture test and functional characterization of
      the large number of RYR1 variants whose precise effects currently remain
      uncertain.

PMID- 25960147
TI  - Heat transfer within hydrodissection fluids: An analysis of thermal conduction
      and convection using liquid and gel materials.
AB  - Interventional oncology procedures such as thermal ablation are becoming widely
      used for many tumours in the liver, kidney and lung. Thermal ablation refers to
      the focal destruction of tissue by generating cytotoxic temperatures in the
      treatment zone. Hydrodissection - separating tissues with fluids - protects
      healthy tissues adjacent to the ablation treatment zone to improve procedural
      safety, and facilitate more aggressive power application or applicator placement.
      However, fluids such as normal saline and 5% dextrose in water (D5W) can migrate
      into the peritoneum, reducing their protective efficacy. As an alternative, a
      thermo-gelable poloxamer 407 (P407) solution has been recently developed to
      facilitate hydrodissection procedures. We hypothesise that the P407 gel material
      does not provide convective heat dissipation from the ablation site, and
      therefore may alter the heat transfer dynamics compared to liquid materials
      during hydrodissection-assisted thermal ablation. The purpose of this study was
      to investigate the heat dissipation mechanics within D5W, liquid P407 and gel
      P407 hydrodissection barriers. Overall it was shown that the gel P407 dissipated
      heat primarily through conduction, whereas the liquid P407 and D5W dissipated
      heat through convection. Furthermore, the rate of temperature change within the
      gel P407 was greater than liquid P407 and D5W. Testing to evaluate the in vivo
      efficacy of the fluids with different modes of heat dissipation seems warranted
      for further study. 

PMID- 25960146
TI  - LA sprouts randomized controlled nutrition and gardening program reduces obesity
      and metabolic risk in Latino youth.
AB  - OBJECTIVE: To assess the effects of a 12-week gardening, nutrition, and cooking
      intervention ("LA Sprouts") on dietary intake, obesity parameters, and metabolic
      disease risk among low-income, primarily Hispanic/Latino youth in Los Angeles.
      METHODS: The randomized controlled trial involved four elementary schools [two
      schools randomized to intervention (172 third-through fifth-grade students); two
      schools randomized to control (147 third-through fifth-grade students)]. Classes
      were taught in 90-minute sessions once a week to each grade level for 12 weeks.
      Data collected at pre- and postintervention included dietary intake via food
      frequency questionnaire (FFQ), anthropometric measures [BMI, waist circumference
      (WC)], body fat, and fasting blood samples. RESULTS: LA Sprouts participants had
      significantly greater reductions in BMI z-scores (0.1-vs. 0.04-point decrease,
      respectively; P = 0.01) and WC (-1.2 cm vs. no change; P < 0.001). Fewer LA
      Sprouts participants had the metabolic syndrome (MetSyn) after the intervention
      than before, while the number of controls with MetSyn increased. LA Sprouts
      participants had improvements in dietary fiber intake (+3.5% vs. -15.5%; P =
      0.04) and less decreases in vegetable intake (-3.6% vs. -26.4%; P = 0.04). Change
      in fruit intake before and after the intervention did not significantly differ
      between LA Sprouts and control subjects. CONCLUSIONS: LA Sprouts was effective in
      reducing obesity and metabolic risk.

PMID- 25960148
TI  - Role of iron oxide core of polymeric nanoparticles in the thermosensitivity of
      colon cancer cell line HT-29.
AB  - PURPOSE: In this study the effect of PLGA polymeric nanoparticles as a 5
      fluorouracil (5-FU) carrier with and without iron oxide core and hyperthermia
      were investigated on the level of DNA damage in a spheroid culture model of HT-29
      colon cancer cell lines by alkaline comet assay. MATERIALS AND METHODS: First, HT
      29 colon cancer cells were cultured in vitro as spheroids with a mean diameter of
      100 um. The spheroids were then treated with different concentrations of 5-FU or
      nanoparticles as 5-FU carriers with and without an iron oxide core for one volume
      doubling time of the spheroids (71 h) and hyperthermia at 43  degrees C for 1 h.
      Finally, the effect of treatment on viability and level of DNA damage was
      examined using trypan blue dye exclusion assay and alkaline comet assay,
      respectively. RESULTS: Results showed that hyperthermia in combination with 5-FU
      or nanoparticles as 5-FU carriers significantly induced the most DNA damage as
      compared with the control group. The extent of DNA damage following treatment
      with 5-FU-loaded nanoparticles combined with hyperthermia was significantly more
      than for 5-FU combined with hyperthermia. In comparison to the effect of 5-FU
      loaded nanoparticles with the iron oxide core and 5-FU-loaded nanoparticle
      without the iron oxide core, the nanoparticles with the iron oxide core combined
      with hyperthermia induced more DNA damage than the nanoparticles without the iron
      oxide core. CONCLUSIONS: According to this study, hyperthermia is a harmful agent
      and nanoparticles are effective delivery vehicles for drugs into colon cancer
      cells. The iron oxide filled nanoparticles increased the effect of the
      hyperthermia. All these factors have a significant role in the treatment of
      colorectal cancer cells.

PMID- 25960149
TI  - Dimerization propensities of Synucleins are not predictive for Synuclein
      aggregation.
AB  - Aggregation and fibril formation of human alpha-Synuclein (alphaS) are
      neuropathological hallmarks of Parkinson's disease and other synucleinopathies.
      The molecular mechanisms of alphaS aggregation and fibrillogenesis are largely
      unknown. Several studies suggested a sequence of events from alphaS dimerization
      via oligomerization and pre-fibrillar aggregation to alphaS fibril formation. In
      contrast to alphaS, little evidence suggests that gammaS can form protein
      aggregates in the brain, and for betaS its neurotoxic properties and aggregation
      propensities are controversially discussed. These apparent differences in
      aggregation behavior prompted us to investigate the first step in Synuclein
      aggregation, i.e. the formation of dimers or oligomers, by Bimolecular
      Fluorescence Complementation in cells. This assay showed some Synuclein-specific
      limitations, questioning its performance on a single cell level. Nevertheless, we
      unequivocally demonstrate that all Synucleins can interact with each other in a
      very similar way. Given the divergent aggregation properties of the three
      Synucleins this suggests that formation of dimers is not predictive for the
      aggregation of alphaS, betaS or gammaS in the aged or diseased brain. 

PMID- 25960151
TI  - Nonrigid groupwise registration for motion estimation and compensation in
      compressed sensing reconstruction of breath-hold cardiac cine MRI.
AB  - PURPOSE: Compressed sensing methods with motion estimation and compensation
      techniques have been proposed for the reconstruction of accelerated dynamic MRI.
      However, artifacts that naturally arise in compressed sensing reconstruction
      procedures hinder the estimation of motion from reconstructed images, especially
      at high acceleration factors. This work introduces a robust groupwise nonrigid
      motion estimation technique applied to the compressed sensing reconstruction of
      dynamic cardiac cine MRI sequences. THEORY AND METHODS: A spatio-temporal
      regularized, groupwise, nonrigid registration method based on a B-splines
      deformation model and a least squares metric is used to estimate and to
      compensate the movement of the heart in breath-hold cine acquisitions and to
      obtain a quasistatic sequence with highly sparse representation in temporally
      transformed domains. RESULTS: Short axis in vivo datasets are used for
      validation, both original multicoil as well as DICOM data. Fully sampled data
      were retrospectively undersampled with various acceleration factors and
      reconstructions were compared with the two well-known methods k-t FOCUSS and
      MASTeR. The proposed method achieves higher signal to error ratio and structure
      similarity index for medium to high acceleration factors. CONCLUSIONS:
      Reconstruction methods based on groupwise registration show higher quality
      reconstructions for cardiac cine images than the pairwise counterparts tested.

PMID- 25960150
TI  - Alzheimer's disease and type 2 diabetes-related alterations in brain
      mitochondria, autophagy and synaptic markers.
AB  - We aimed to investigate mitochondrial function, biogenesis and autophagy in the
      brain of type 2 diabetes (T2D) and Alzheimer's disease (AD) mice. Isolated brain
      mitochondria and homogenates from cerebral cortex and hippocampus of wild-type
      (WT), triple transgenic AD (3xTg-AD) and T2D mice were used to evaluate
      mitochondrial functional parameters and protein levels of mitochondrial
      biogenesis, autophagy and synaptic integrity markers, respectively. A significant
      decrease in mitochondrial respiration, membrane potential and energy levels was
      observed in T2D and 3xTg-AD mice. Also, a significant decrease in the levels of
      autophagy-related protein 7 (ATG7) and glycosylated lysosomal membrane protein 1
      (LAMP1) was observed in cerebral cortex and hippocampus of T2D and 3xTg-AD mice.
      Moreover, both brain regions of 3xTg-AD mice present lower levels of nuclear
      respiratory factor (NRF) 1 while the levels of NRF2 are lower in both brain
      regions of T2D and 3xTg-AD mice. A decrease in mitochondrial encoded,
      nicotinamide adenine dinucleotide dehydrogenase subunit 1 (ND1) was also observed
      in T2D and 3xTg-AD mice although only statistically significant in T2D cortex.
      Furthermore, a decrease in the levels of postsynaptic density protein 95 (PSD95)
      in the cerebral cortex of 3xTg-AD mice and in hippocampus of T2D and 3xTg-AD mice
      and a decrease in the levels of synaptosomal-associated protein 25 (SNAP 25) in
      the hippocampus of T2D and 3xTg-AD mice were observed suggesting synaptic
      integrity loss. These results support the idea that alterations in mitochondrial
      function, biogenesis and autophagy cause synaptic damage in AD and T2D. 

PMID- 25960152
TI  - In patients with myelodysplastic syndromes with del(5q), factors other than age
      and sex contribute to the prognostic advantage, which diminishes over time.
AB  - This study aimed to determine the extent to which the prognostic advantage of
      myelodysplastic syndromes (MDS) with del(5q) is due to the more favourable age
      and sex distribution of patients in that group when compared to other MDS
      subtypes. A total of 1912 MDS patients from the Duesseldorf registry with less
      than 5% blasts in the bone marrow were evaluable and had complete covariates. As
      endpoints, overall survival and progression to acute myeloid leukaemia (AML) were
      considered. Cox models were computed for both outcomes. A multivariate Cox model
      for survival confirmed higher age and male sex as risk factors. In addition, we
      found a survival advantage of 9.1 years for MDS del(5q) patients compared to
      refractory cytopenia with unilineage dysplasia, while the survival advantage of
      MDS del(5q) over refractory cytopenia with multilineage dysplasia was 18.6 years.
      Considering progression to AML, we did not find any significant differences
      between the World Health Organization classification subtypes. Our analyses show
      that the higher survival probabilities of MDS del(5q) patients are not only due
      to age and sex, although higher age and male sex were also important risk
      factors. Interestingly, it seems that the survival advantage of MDS del(5q)
      decreases over time. 

PMID- 25960153
TI  - Melatonin induces nitric oxide and the potential mechanisms relate to innate
      immunity against bacterial pathogen infection in Arabidopsis.
AB  - Melatonin (N-acetyl-5-methoxytryptamine) is a naturally occurring small molecule,
      serving as important secondary messenger in the response of plants to various
      biotic and abiotic stresses. However, the interactions between melatonin and
      other important molecules in the plant stress response, especially in plant
      immunity, are largely unknown. In this study, we found that both melatonin and
      nitric oxide (NO) levels in Arabidopsis leaves were significantly induced by
      bacterial pathogen (Pst DC3000) infection. The elevated NO production was caused
      by melatonin as melatonin application enhanced endogenous NO level with great
      efficacy. Moreover, both melatonin and NO conferred improved disease resistance
      against Pseudomonas syringe pv. tomato (Pst) DC3000 infection in Arabidopsis. NO
      scavenger significantly suppressed the rise of NO which was induced by exogenous
      application of melatonin. As a result, the beneficial effects of melatonin on the
      expression of salicylic acid (SA)-related genes and disease resistance against
      bacterial pathogen infection were jeopardized by use of a NO scavenger.
      Consistently, melatonin application significantly lost its effect on the innate
      immunity against P. syringe pv. tomato (Pst) DC3000 infection in NO-deficient
      mutants of Arabidopsis. The results indicate that melatonin-induced NO production
      is responsible for innate immunity response of Arabidopsis against Pst DC3000
      infection. 

PMID- 25960154
TI  - The development of a nucleus staining fluorescent probe for dynamic mitosis
      imaging in live cells.
AB  - A low-toxicity nucleus staining fluorescent probe, , was developed for real time
      mitosis imaging in live cells. was identified by unbiased high-throughput imaging
      based screening of a new xanthone library (AX). Unlike the conventional Hoechst
      dye, the low toxicity of allows long term monitoring of cell division over more
      than one cell cycle. 

PMID- 25960155
TI  - Acute suppurative oligoarthritis and osteomyelitis: a differential diagnosis that
      overlaps with acute rheumatic fever.
AB  - BACKGROUND: Acute rheumatic fever (ARF) is an illness caused by group A
      streptococcus (GAS) infection, and remains the leading cause of acquired heart
      disease in worldwide. Distinguishing between ARF and septic arthritis may be
      difficult. This report describes a case of suppurative arthritis overlapping with
      ARF. CASE PRESENTATION: A 4-year-old, previously healthy boy presented with fever
      and left leg pain. The level of anti-streptolysin O (ASO) was elevated. His
      throat swab cultures grew GAS, but none were detected in his synovial fluid.
      Magnetic resonance imaging revealed suspected arthritis and osteomyelitis. The
      patient was treated for septic arthritis, but was subsequently diagnosed with
      ARF, after the development of carditis. CONCLUSION: The clinical and laboratory
      features of ARF and suppurative arthritis demonstrate substantial overlap.
      Patients with an elevated ASO should undergo a careful cardiac examination for
      carditis associated with ARF by an echocardiogram.

PMID- 25960156
TI  - Evaluation of the Etest method for detecting colistin susceptibility of multidrug
      resistant Gram-negative isolates in Vietnam.
AB  - The minimum inhibitory concentrations (MICs) of colistin for 241 multidrug
      resistant (MDR) Gram-negative pathogens were determined by the Etest and by the
      broth microdilution method (BMD). The two methods showed essential agreements of
      76% (77/102) for Acinetobacter baumannii, 90% (36/40) for Pseudomonas aeruginosa
      and 84% (83/99) for Enterobacteriaceae isolates, with categorical agreements of
      100%, 98%, and 100%, respectively. Of the 241 isolates, none showed a very major
      error and one (0.4%) showed a major error. MICs ranged from 0.125 to 0.5 MUg/ml
      for all A. baumannii and most Enterobacteriaceae isolates, and from 1 to 2 MUg/ml
      for most P. aeruginosa isolates. Of the 40 P. aeruginosa isolates, 27 (68%)
      showed higher colistin MICs by the Etest than by the BMD. In contrast, 77%
      (78/102) of the A. baumannii and 57% (56/99) of the Enterobacteriaceae isolates
      showed lower colistin MICs by the Etest than by the BMD. The Etest is a reliable
      and easy-to-use method to measure colistin MICs of MDR Gram-negative pathogens in
      clinical laboratories and can be used following validation by microdilution
      methods. 

PMID- 25960158
TI  - TravWell--The latest CDC app for travellers.

PMID- 25960157
TI  - Respecting Autonomy Over Time: Policy and Empirical Evidence on Re-Consent in
      Longitudinal Biomedical Research.
AB  - Re-consent in research, the asking for a new consent if there is a change in
      protocol or to confirm the expectations of participants in case of change, is an
      under-explored issue. There is little clarity as to what changes should trigger
      re-consent and what impact a re-consent exercise has on participants and the
      research project. This article examines applicable policy statements and
      literature for the prevailing arguments for and against re-consent in relation to
      longitudinal cohort studies, tissue banks and biobanks. Examples of re-consent
      exercises are presented, triggers and non-triggers for re-consent discussed and
      the conflicting attitudes of commentators, participants and researchers
      highlighted. We acknowledge current practice and argue for a greater emphasis on
      'responsive autonomy,' that goes beyond a one-time consent and encourages greater
      communication between the parties involved. A balance is needed between
      respecting participants' wishes on how they want their data and samples used and
      enabling effective research to proceed. 

PMID- 25960159
TI  - BMI and coronary heart disease: no difference according to sex.

PMID- 25960161
TI  - Revealing the synergetic effects in Ni nanoparticle-carbon nanotube hybrids by
      scanning transmission X-ray microscopy and their application in the hydrolysis of
      ammonia borane.
AB  - The hybrids of carbon nanotubes (CNTs) and the supported Ni nanoparticles (NPs)
      have been studied by scanning transmission X-ray microscopy (STXM) and tested by
      the hydrolysis reaction of ammonia borane (AB, NH3BH3). Data clearly showed the
      existence of a strong interaction between Ni NPs and thin CNTs (C-O-Ni bonds),
      which favored the tunable (buffer) electronic structure of Ni NPs facilitating
      the catalytic process. The hydrolysis process of AB confirmed the hypothesis that
      the hybrids with a strong interfacial interaction would show superior catalytic
      performance, while the hybrids with a weak interfacial interaction show poor
      performance. Our results provide a wealth of detailed information regarding the
      electronic structure of the NP-CNT hybrids and provide guidance towards the
      rational design of high-performance catalysts for energy applications. 

PMID- 25960162
TI  - Quality of fresh organic matter affects priming of soil organic matter and
      substrate utilization patterns of microbes.
AB  - Changes in biogeochemical cycles and the climate system due to human activities
      are expected to change the quantity and quality of plant litter inputs to soils.
      How changing quality of fresh organic matter (FOM) might influence the priming
      effect (PE) on soil organic matter (SOM) mineralization is still under debate.
      Here we determined the PE induced by two (13)C-labeled FOMs with contrasting
      nutritional quality (leaf vs. stalk of Zea mays L.). Soils from two different
      forest types yielded consistent results: soils amended with leaf tissue switched
      faster from negative PE to positive PE due to greater microbial growth compared
      to soils amended with stalks. However, after 16 d of incubation, soils amended
      with stalks had a higher PE than those amended with leaf. Phospholipid fatty acid
      (PLFA) results suggested that microbial demand for carbon and other nutrients was
      one of the major determinants of the PE observed. Therefore, consideration of
      both microbial demands for nutrients and FOM supply simultaneously is essential
      to understand the underlying mechanisms of PE. Our study provided evidence that
      changes in FOM quality could affect microbial utilization of substrate and PE on
      SOM mineralization, which may exacerbate global warming problems under future
      climate change. 

PMID- 25960163
TI  - Contact dermatitis caused by brazilin in Caesalpinia sappan.

PMID- 25960160
TI  - The sex-specific association between BMI and coronary heart disease: a systematic
      review and meta-analysis of 95 cohorts with 1.2 million participants.
AB  - BACKGROUND: The risk of developing coronary heart disease differs by sex, and
      accumulating evidence suggests that sex differences exist in the effect of
      coronary risk factors on vascular risk. So far, the existence of a sex difference
      in the association between BMI and coronary heart disease has not been
      systematically studied. Since sexual dimorphisms in body composition exist, we
      postulated that the association between BMI and coronary heart disease would
      differ between women and men. METHODS: We did systematic searches of PubMed and
      Embase up to Feb 20, 2015, for studies of the longitudinal association between
      BMI and coronary heart disease in women and men from population-based cohorts. We
      excluded studies if they contained duplicate data from the same study, reported
      estimates only for Z scores or percentiles of BMI, did not report estimate
      uncertainty, did not report sex-specific estimates, recruited mainly individuals
      with a previous history of cardiovascular disease or from within selected
      populations, and those for which the full text was not available in English. We
      also included individual participant data from four large studies. Study results
      were pooled using random-effect models with inverse variance weighting. Our
      predefined primary endpoint was the pooled women-to-men ratio of the age-adjusted
      hazard ratios (HRs), or equivalent, relating (continuous and categorical) BMI to
      coronary heart disease. FINDINGS: We reviewed a total of 8561 original entries
      twice for inclusion in the analysis, of which 32 published studies were eligible
      for inclusion. Data from 95 cohorts, 1,219,187 participants, and 37,488 incident
      cases of coronary heart disease were included. Higher BMI was significantly
      associated with age-adjusted coronary heart disease: for a one-unit (kg/m(2))
      increment in BMI; the HR was 1.04 (95% CI 1.03-1.05) in women and 1.05 (1.04
      1.07) in men. Compared with people of a normal weight, the age-adjusted HR of
      coronary heart disease for the underweight group was 1.25 (1.05-1.49) in women
      and 1.09 (0.91-1.23) in men; for the overweight group 1.20 (1.12-1.29) in women
      and 1.22 (1.12-1.32) in men; and for the obese group 1.61 (1.42-1.82) in women
      and 1.60 (1.43-1.79) in men. Overall, these associations did not differ between
      the sexes. The women-to-men ratios of the HRs were 0.99 (95% CI 0.98-1.00) for a
      one-unit increment in BMI, 1.10 (0.91-1.32) for the underweight group, 0.99 (0.92
      1.07) for the overweight group, and 1.06 (0.95-1.17) for the obese group,
      relative to the normal weight group. Similar results were obtained after multiple
      adjustment and in a range of sensitivity analyses. INTERPRETATION: Increased BMI,
      measured either continuously or categorically, has the same deleterious effects
      on the risk of coronary heart disease in women and men across diverse
      populations. FUNDING: None.

PMID- 25960164
TI  - The activation of type 1 corticotropin releasing factor receptor (CRF-R1)
      inhibits proliferation and promotes differentiation of neuroblastoma cells in
      vitro via p27(Kip1) protein up-regulation and c-Myc mRNA down-regulation.
AB  - Our group has previously shown that corticotropin releasing factor (CRF) inhibits
      proliferation of human endocrine-related cancer cell lines via the activation of
      CRF type-1 receptors (CRF-R1). Tumors originating from the nervous system also
      express CRF receptors but their role on neoplastic cell proliferation was poorly
      investigated. Here we investigated the effect of CRF receptor stimulation on
      nervous system-derived cancer cells, using the SK-N-SH (N) human neuroblastoma
      cell line as an experimental model. We found that SK-N-SH (N) cells express
      functionally active CRF-R1, whose activation by CRF and the cognate peptide
      urocortin (UCN) is associated to reduced cell proliferation and motility, as well
      as neuronal-like differentiation. UCN did not interfere with cell viability and
      cell-cycle arrest. Those effects seem to be mediated by a mechanism involving the
      activation of cAMP/PKA/CREB pathway and the subsequent downstream increase in
      p27(Kip1) and underphosphorylated retinoblastoma protein levels, as well as
      reduced c-Myc mRNA accumulation. 

PMID- 25960166
TI  - Aetiological coding sequence variants in non-syndromic premature ovarian failure:
      From genetic linkage analysis to next generation sequencing.
AB  - Premature ovarian failure (POF) is a frequent pathology affecting 1-1.5% of women
      under 40 years old. Despite advances in diagnosing and treating human
      infertility, POF is still classified as being idiopathic in 50-80% of cases,
      strongly suggesting a genetic origin for the disease. Different types of
      autosomal and X-linked genetic anomalies can originate the phenotype in syndromic
      and non-syndromic POF cases. Particular interest has been focused on research
      into non-syndromic POF causative coding variants during the past two decades.
      This has been based on the assumption that amino acid substitutions might modify
      the intrinsic physicochemical properties of functional proteins, thereby inducing
      pathological phenotypes. In this case, a restricted number of mutations might
      originate the disease. However, like other complex pathologies, POF might result
      from synergistic/compensatory effects caused by several low-to-mildly drastic
      mutations which have frequently been classified as non-functional SNPs. Indeed,
      reproductive phenotypes can be considered as quantitative traits resulting from
      the subtle interaction of many genes. Although numerous sequencing projects have
      involved candidate genes, only a few coding mutations explaining a low percentage
      of cases have been described. Such apparent failure to identify aetiological
      coding sequence variations might have been due to the inherent molecular
      complexity of mammalian reproduction and to the difficulty of simultaneously
      analysing large genomic regions by Sanger sequencing. The purpose of this review
      is to present the molecular and cellular effects caused by non-synonymous
      mutations which have been formally associated, by functional tests, with the
      aetiology of hypergonadotropic non-syndromic POF. Considerations have also been
      included regarding the polygenic nature of reproduction and POF, as well as
      future approaches for identifying novel aetiological genes based on next
      generation sequencing (NGS). 

PMID- 25960165
TI  - Anandamide restricts uterine stromal differentiation and is critical for complete
      decidualization.
AB  - The major endocannabinoid, anandamide (AEA), is widely distributed in the body,
      especially in the reproductive tissues, where it is implicated in early pregnancy
      events, particularly during implantation period. Although AEA is synthesized in
      decidual cells and showed to induce apoptosis through CB1 receptor, its roles in
      decidualization remain to be elucidated. This study examined the effect of AEA in
      the progression of decidualization both in vitro and in vivo and explored the
      involvement of COX-2 in its action. To determine the function of AEA during this
      differentiation process, we employed a primary culture system in which
      undifferentiated stromal cells isolated from pregnant rat uterus undergo
      decidualization. AEA treatment markedly interfered with the differentiation
      program, as revealed by alpha2-macroglobulin (alpha2-MG) expression and alkaline
      phosphatase activity. Additionally, it was evaluated the effects of AEA in
      decidual establishment in the pseudopregnant rat model. The abundance of AEA in
      the uterine lumen disrupted the decidualization process accompanied by a
      decreased expression of COX-2 and VEGF. It was also observed that uterine lumen,
      which failed the progression of decidualization in response to AEA, also
      presented lower expression of NAPE-PLD and FAAH. Thus, the mechanisms by which
      AEA inhibits decidualization can be either via direct actions on stromal cell
      differentiation within the reproductive tract system or by the inhibition of COX
      2 derived products and, consequently, the vascular remodeling required to proper
      decidualization. In addition, the previous observations showing that higher AEA
      levels in pre-implantation sites are hostile to blastocyst survival may result
      from problems in decidual cell reaction more than with implantation failure. 

PMID- 25960167
TI  - Impact of cardiac magnetic resonance imaging on eosinophilic granulomatosis with
      polyangiitis outcomes: A long-term retrospective study on 42 patients.
AB  - OBJECTIVE: To determine the diagnostic and prognostic significance of cardiac
      magnetic resonance imaging (CMRI) in a cohort of patients with eosinophilic
      granulomatosis with polyangiitis (EGPA). METHODS: We conducted a monocentric
      retrospective study including 42 EGPA patients who had consecutively undergone
      CMRI at diagnosis or during follow-up, independently of signs of cardiac
      involvement. RESULTS: Forty-two patients (male 59.5%, mean age at diagnosis 46.5
      years) were included. ANCA was positive in 26.2%, and median EGPA duration before
      the 1st CMRI screening was 5 months. Seventeen (40.5%) were diagnosed with
      cardiomyopathy, independently of CMRI findings. CMRI showed myocardial late
      gadolinium enhancement (LGE) in 82.4% patients with cardiomyopathy vs. 44%
      without cardiomyopathy (P=0.024). Using LGE as the sole criterion, CMRI
      sensitivity and specificity for diagnosing cardiomyopathy were 82.4% and 56%,
      respectively. Among the 15 patients with cardiomyopathy who underwent additional
      CMRI during follow-up, CMRI-detected cardiac lesions had improved in 7 patients,
      while those of 8 patients worsened or stabilized despite treatment. These latter
      patients presented with significantly more cardiac events during follow-up
      (P=0.026). No differences were found between non-cardiomyopathic patients with or
      without CMRI anomalies concerning EGPA cardiac manifestations and outcomes.
      CONCLUSION: The diagnostic significance of myocardial LGE in EGPA patients
      remains uncertain and should not be the only criterion for cardiomyopathy
      diagnosis. For patients with no other signs of cardiomyopathy, CMRI-detected
      anomalies do not seem to adversely affect prognosis or outcome. For patients with
      cardiomyopathy, CMRI reassessment seems promising in detecting patients with a
      less favorable cardiac outcome.

PMID- 25960169
TI  - Novel targets for the prevention of osteoporosis - lessons learned from studies
      of metabolic bone disorders.
AB  - INTRODUCTION: Osteoporosis is a major health care problem, and whereas
      efficacious treatments for vertebral fracture reduction are available for
      osteoporosis patients, these therapies are still limited with respect to capacity
      for restoration of bone loss, as well as efficacy on non-vertebral fractures,
      such as hip fractures, which are the source of morbidity and mortality. AREAS
      COVERED: Studies of rare bone diseases in humans, such as osteopetrosis,
      sclerosteosis, pycnodysostosis and more, have shed light on a series of drug
      targets in bone that have the potential to result in therapies for osteoporosis
      with novel mechanisms of action, and the potential to improve the standard of
      care substantially. We focus on how they are separated from classic treatments
      for osteoporosis, in terms of novel modes of action, additional beneficial
      effects on bone turnover and importantly also safety. We focus on the status of
      anti-sclerostin antibodies, novel parathyroid hormone-related protein analogs,
      inhibitors of cathepsin K and ClC-7 in osteoclasts, all of which are currently in
      development. EXPERT OPINION: There is a good possibility that the treatment of
      osteoporosis will be greatly improved within the coming years; however, with
      numerous effective and safe drugs already available careful attention to the
      safety of these novel candidates is crucial.

PMID- 25960168
TI  - Increased and safer detection of nonrecurrent inferior laryngeal nerve after
      preoperative ultrasonography.
AB  - OBJECTIVES/HYPOTHESIS: Right nonrecurrent inferior laryngeal nerve (NRLN) is an
      anatomical variant reported with a variable prevalence (0.3%-6%). It is
      associated with some arterial abnormalities (absence of the brachiocephalic trunk
      and presence of a right aberrant subclavian lusorian artery) that may be
      identified by preoperative ultrasonography (pUS). NRLN represents a major
      morbidity risk factor during neck surgery. The aim of this study was to verify
      pUS accuracy in predicting NRLN and to assess the impact of this technique on
      NRLN detection rate and laryngeal morbidity. STUDY DESIGN: Retrospective.
      METHODS: The study included 1,477 patients undergoing thyroid and parathyroid
      surgery with right-side inferior laryngeal nerve exploration. pUS was performed
      in 878 patients (pUS group); no preoperative attempts were performed in the
      remaining 599 patients (controls). Demographics, disease type, intraoperative
      inferior laryngeal nerve anatomy, and laryngeal morbidity were compared. RESULTS:
      No differences occurred between the two groups concerning demographics and
      disease type. NRLN was detected in 17 patients (1.9%) of the pUS group and in
      four patients (0.6%) of controls (P < 0.05). pUS predicted NRLN in all cases,
      with an overall accuracy > 98%. Overall laryngeal nerves morbidity was 1.8% in
      the pUS group and 4.2% in the controls (P < 0.05). NRLN palsy never occurred in
      the pUS group, whereas it occurred three times in the controls (P < 0.005).
      CONCLUSION: NRLN is accurately predicted by pUS. It occurs more frequently than
      expected because it may be misdiagnosed when no preoperative suspicion is
      available. Preoperative NRLN detection by pUS prevents inferior laryngeal nerve
      injuries.

PMID- 25960170
TI  - Erythematous vesiculopapular eruptions on the extremities.

PMID- 25960171
TI  - Room temperature ring expansion of N-heterocyclic carbenes and B-B bond cleavage
      of diboron(4) compounds.
AB  - We report the isolation and detailed structural characterization, by solid-state
      and solution NMR spectroscopy, of the neutral mono- and bis-NHC adducts of
      bis(catecholato)diboron (B2 cat2 ). The bis-NHC adduct undergoes thermally
      induced rearrangement, forming a six-membered -B-C=N-C=C-N-heterocyclic ring via
      C-N bond cleavage and ring expansion of the NHC, whereas the mono-NHC adduct is
      stable. Bis(neopentylglycolato)diboron (B2 neop2 ) is much more reactive than B2
      cat2 giving a ring expanded product at room temperature, demonstrating that ring
      expansion of NHCs can be a very facile process with significant implications for
      their use in catalysis.

PMID- 25960172
TI  - Pulmonary hypertension in HIV infection: a prospective echocardiographic study.
AB  - OBJECTIVES: While idiopathic pulmonary arterial hypertension (PAH) is a rare
      disease, it is seen more frequently in patients with HIV infection. The aim of
      this study was to evaluate the prevalence of pulmonary hypertension (PH) in
      patients with HIV infection by echocardiographic screening. METHODS:
      Echocardiography and N-terminal of the prohormone brain natriuretic peptide
      measurement were used to examine the prevalence of PH prospectively in HIV
      positive patients (n = 374) during routine follow-up visits for HIV disease.
      RESULTS: In echocardiographic screening, PH was detected in a total of 23 of 374
      HIV-infected patients (6.1%). Of these, three patients (13%) presented with
      symptoms of dyspnoea and fatigue, and diagnosis of PAH was confirmed by right
      heart catheterization. Patients with systolic pulmonary artery pressure (sPAP) >
      30 mmHg were more likely to be female, to have a history of injecting drug use
      and to originate from high-prevalence countries (HPCs). CONCLUSIONS:
      Echocardiographic screening detected PH in a substantial proportion of HIV
      positive patients. Female gender, a history of injecting drug use and HPC origin
      were associated with a higher prevalence of HIV-associated PH. The relevance and
      long-term outcome of these findings need to be validated in follow-up studies,
      which are ongoing.

PMID- 25960174
TI  - Confocal laser endomicroscopy to monitor the colonic mucosa of mice.
AB  - The gastrointestinal tract is a unique organ system that provides an epithelial
      barrier between our underlying immune system and luminal pathogens. Disruption of
      gastrointestinal homeostasis, as a result of impaired barrier function, is
      associated with numerous pathologies including inflammatory bowel disease and
      colorectal cancer. In parallel to the clinical development of endoscopy
      technologies to monitor and diagnose these pathologies in humans, advanced mouse
      colonoscopy techniques are being developed. When these technologies are coupled
      with model systems of human disease, which are essential to our understanding of
      the pathophysiology of gastrointestinal diseases, the requirement for euthanasia
      of multiple cohorts of mice is eliminated. Here we highlight the suitability of
      white light endoscopy to monitor the progression of colitis in mice. We further
      outline the experimental power of combined standard endoscopy with confocal
      microendoscopy, which permits visualization of fluorescent markers in a single
      animal in real-time. Together, these technologies will enhance our understanding
      of the interplay between components of the gastrointestinal microenvironment and
      their role in disease. 

PMID- 25960173
TI  - Cytokine release assays for the prediction of therapeutic mAb safety in first-in
      man trials--Whole blood cytokine release assays are poorly predictive for TGN1412
      cytokine storm.
AB  - The therapeutic monoclonal antibody (mAb) TGN1412 (anti-CD28 superagonist) caused
      near-fatal cytokine release syndrome (CRS) in all six volunteers during a phase-I
      clinical trial. Several cytokine release assays (CRAs) with reported predictivity
      for TGN1412-induced CRS have since been developed for the preclinical safety
      testing of new therapeutic mAbs. The whole blood (WB) CRA is the most widely
      used, but its sensitivity for TGN1412-like cytokine release was recently
      criticized. In a comparative study, using group size required for 90% power with
      5% significance as a measure of sensitivity, we found that WB and 10% (v/v) WB
      CRAs were the least sensitive for TGN1412 as these required the largest group
      sizes (n = 52 and 79, respectively). In contrast, the peripheral blood
      mononuclear cell (PBMC) solid phase (SP) CRA was the most sensitive for TGN1412
      as it required the smallest group size (n = 4). Similarly, the PBMC SP CRA was
      more sensitive than the WB CRA for muromonab-CD3 (anti-CD3) which stimulates
      TGN1412-like cytokine release (n = 4 and 4519, respectively). Conversely, the WB
      CRA was far more sensitive than the PBMC SP CRA for alemtuzumab (anti-CD52) which
      stimulates FcgammaRI-mediated cytokine release (n = 8 and 180, respectively).
      Investigation of potential factors contributing to the different sensitivities
      revealed that removal of red blood cells (RBCs) from WB permitted PBMC-like
      TGN1412 responses in a SP CRA, which in turn could be inhibited by the addition
      of the RBC membrane protein glycophorin A (GYPA); this observation likely
      underlies, at least in part, the poor sensitivity of WB CRA for TGN1412. The use
      of PBMC SP CRA for the detection of TGN1412-like cytokine release is recommended
      in conjunction with adequately powered group sizes for dependable preclinical
      safety testing of new therapeutic mAbs.

PMID- 25960175
TI  - Identification of T cell clones without the need for sequencing.
AB  - The brainbow recombination fluorescent protein system has been used for a
      multitude of applications in fate and lineage tracking. Here, we use a mouse with
      a ubiquitously expressed brainbow construct, termed the Confetti mouse, to
      perform T lymphocyte cell lineage tracking. We demonstrate that antigen-specific
      T lymphocyte clonotypes can be identified and phenotyped using flow cytometry
      instead of performing expensive and time-consuming methods of single cell
      sequencing. 

PMID- 25960176
TI  - A fully-automated, six-plex single molecule immunoassay for measuring cytokines
      in blood.
AB  - We report a system and assay for performing fully-automated measurement of 6
      proteins simultaneously with single molecule sensitivity. The system combines
      handling of samples, reagents, and consumables, with a module for imaging single
      molecule arrays (Simoa) to enable immunoassays that have high sensitivity
      (~fg/mL), are multiplexed, and are fully-automated. A 6-plex cytokine Simoa assay
      for IL-6, TNF-alpha, GM-CSF, IL-10, IL-1beta, and IL-1alpha was developed on the
      system. The assays had limits of detection in the range 0.01-0.03pg/mL, and the
      average imprecision (CV) of the Simoa signal was 4.2%. This assay was used to
      measure the concentrations of these cytokines in the plasma of patients with
      Crohn's Disease (CD), before and after treatment with anti-TNF-alpha antibody
      drugs, and in the serum of Type 1 diabetics. Concentrations of TNF-alpha and IL-6
      in the CD samples determined using the fully-automated, multiplex Simoa assay had
      good correlation with the manual, single-plex assays previously reported. Drug
      treatment caused reductions in the mean concentration of all 6 cytokines in the
      plasma of CD patients. The concentrations of 4 cytokines were significantly
      higher in diabetics compared to healthy controls. The system could enable the
      widespread, multiplexed measurement of protein biomarkers with low abundance. 

PMID- 25960177
TI  - Hydroxyethylene isosteres introduced in type II collagen fragments substantially
      alter the structure and dynamics of class II MHC A(q)/glycopeptide complexes.
AB  - Class II major histocompatibility complex (MHC) proteins are involved in
      initiation of immune responses to foreign antigens via presentation of peptides
      to receptors of CD4(+) T-cells. An analogous presentation of self-peptides may
      lead to autoimmune diseases, such as rheumatoid arthritis (RA). The glycopeptide
      fragment CII259-273, derived from type II collagen, is presented by A(q) MHCII
      molecules in the mouse and has a key role in development of collagen induced
      arthritis (CIA), a validated model for RA. We have introduced hydroxyethylene
      amide bond isosteres at the Ala(261)-Gly(262) position of CII259-273. Biological
      evaluation showed that A(q) binding and T cell recognition were dramatically
      reduced for the modified glycopeptides, although static models predicted similar
      binding modes as the native type II collagen fragment. Molecular dynamics (MD)
      simulations demonstrated that introduction of the hydroxyethylene isosteres
      disturbed the entire hydrogen bond network between the glycopeptides and A(q). As
      a consequence the hydroxyethylene isosteric glycopeptides were prone to
      dissociation from A(q) and unfolding of the beta1-helix. Thus, the isostere
      induced adjustment of the hydrogen bond network altered the structure and
      dynamics of A(q)/glycopeptide complexes leading to the loss of A(q) affinity and
      subsequent T cell response. 

PMID- 25960178
TI  - Electrospun type 1 collagen matrices preserving native ultrastructure using
      benign binary solvent for cardiac tissue engineering.
AB  - Electrospinning is a well-established technique that uses a high electric field
      to fabricate ultrafine fibrous scaffolds from both natural and synthetic polymers
      to mimic the cellular microenvironment. Collagen is one of the most preferred
      biopolymers, due to its widespread occurrence in nature and its biocompatibility.
      Electrospinning of collagen alone has been reported, with fluoroalcohols such as
      hexafluoroisopropanol (HFIP) and trifluoroethanol (TFE), but the resultant
      collagen lost its characteristic ultrastructural integrity of D-periodicity 67 nm
      banding, confirmed by transmission electron microscopy (TEM), and the
      fluoroalcohols used were toxic to the environment. In this study, we describe the
      use of glacial acetic acid and DMSO to dissolve collagen and generate electrospun
      nanofibers of collagen type 1, which is non-toxic and economical. TEM analysis
      revealed the characteristic feature of native collagen triple helical repeats,
      showing 67 nm D-periodicity banding pattern and confirming that the
      ultrastructural integrity of the collagen was maintained. Analysis by scanning
      electron microscopy (SEM) showed fiber diameters in the range of 200-1100 nm.
      Biocompatibility of the three-dimensional (3D) scaffolds was established by MTT
      assays using rat skeletal myoblasts (L6 cell line) and confocal microscopic
      analysis of immunofluorescent-stained sections of collagen scaffolds for muscle
      specific markers such as desmin and actin. Primary neonatal rat ventricular
      cardiomyocytes (NRVCM) seeded onto the collagen scaffolds were able to maintain
      their contractile function for a period of 17 days and also expressed higher
      levels of desmin when compared with 2D cultures. We report for the first time
      that collagen type 1 can be electrospun without blending with copolymers using
      the novel benign solvent combination, and the method can be potentially explored
      for applications in tissue engineering. 

PMID- 25960179
TI  - Development and characterization of floating spheroids of atorvastatin calcium
      loaded NLC for enhancement of oral bioavailability.
AB  - OBJECTIVE: The obejctive of the present study was to investigate the potential
      use of floating spheroids of Atorvastatin Calcium (ATS) Loaded nanostructured
      lipid carriers (NLCs). MATERIALS AND METHODS: The final formula of floating
      spheroids was optimized on the basis of shape (spherical), diameter (0.47 mm),
      lag time (20 s), and floating time (> 32 h). RESULTS: The results were further
      confirmed by different pharmacokinetic parameters-it was observed that the
      developed optimized floating ATS spheroid-loaded NLCs formulation has
      significantly improved relative bioavailability, that is, 3.053-folds through
      oral route in comparison to marketed formulation.

PMID- 25960180
TI  - Hybrid nanostructures for SERS: materials development and chemical detection.
AB  - This review focuses on recent developments in hybrid and nanostructured
      substrates for SERS (surface-enhanced Raman scattering) studies. Thus substrates
      composed of at least two distinct types of materials, in which one is a SERS
      active metal, are considered here aiming at their use as platforms for chemical
      detection in a variety of contexts. Fundamental aspects related to the SERS
      effect and plasmonic behaviour of nanometals are briefly introduced. The
      materials described include polymer nanocomposites containing metal nanoparticles
      and coupled inorganic nanophases. Chemical approaches to tailor the morphological
      features of these substrates in order to get high SERS activity are reviewed.
      Finally, some perspectives for practical applications in the context of chemical
      detection of analytes using such hybrid platforms are presented. 

PMID- 25960182
TI  - Stable and efficient hole transporting materials with a dimethylfluorenylamino
      moiety for perovskite solar cells.
AB  - Novel star-shaped hole transporting materials (HTMs) with a bis
      dimethylfluorenylamino moiety have been synthesized and evaluated for high
      performance perovskite solar cell applications. Maximum power conversion
      efficiency of 14.21% has been achieved by using the HTM with a fused TPA core and
      the long-term stability was also shown to be comparable with that of . 

PMID- 25960181
TI  - A proteomic approach to obesity and type 2 diabetes.
AB  - The incidence of obesity and type diabetes 2 has increased dramatically resulting
      in an increased interest in its biomedical relevance. However, the mechanisms
      that trigger the development of diabetes type 2 in obese patients remain largely
      unknown. Scientific, clinical and pharmaceutical communities are dedicating vast
      resources to unravel this issue by applying different omics tools. During the
      last decade, the advances in proteomic approaches and the Human Proteome
      Organization have opened and are opening a new door that may be helpful in the
      identification of patients at risk and to improve current therapies. Here, we
      briefly review some of the advances in our understanding of type 2 diabetes that
      have occurred through the application of proteomics. We also review, in detail,
      the current improvements in proteomic methodologies and new strategies that could
      be employed to further advance our understanding of this pathology. By applying
      these new proteomic advances, novel therapeutic and/or diagnostic protein targets
      will be discovered in the obesity/Type 2 diabetes area. 

PMID- 25960185
TI  - The influence of cholesterol precursor--desmosterol--on artificial lipid
      membranes.
AB  - The disorders in cholesterol biosynthesis pathway and various diseases manifest
      in the accumulation of cholesterol precursors in the human tissues and cellular
      membranes. In this paper the effect of desmosterol--one of cholesterol precursors
      -on model lipid membranes was studied. The investigations were performed for
      binary SM/desmo and POPC/desmo and ternary SM/POPC/desmo monolayers. Moreover,
      the experiments based on the gradual substitution of cholesterol by desmosterol
      in SM/POPC/chol=1:1:1 system were done. The obtained results allowed one to
      conclude that desmosterol is of lower domains promoting and stabilizing
      properties and packs less tightly with the lipids in monolayers. Moreover,
      desmosterol probably could replace cholesterol in model membranes, but only at
      its low proportion in the system (2%), however, at a higher degree of cholesterol
      substitution a significant decrease of the monolayer stability and packing and
      alterations in the film morphology were detected. The results collected in this
      work together with those from previous experiments allowed one to analyze the
      effect of a double bond in the sterol side chain as well as its position in the
      ring system on membrane activity of the molecule and to verify Bloch hypothesis.

PMID- 25960183
TI  - C-H activation generates period-shortening molecules that target cryptochrome in
      the mammalian circadian clock.
AB  - The synthesis and functional analysis of KL001 derivatives, which are modulators
      of the mammalian circadian clock, are described. By using cutting-edge C-H
      activation chemistry, a focused library of KL001 derivatives was rapidly
      constructed, which enabled the identification of the critical sites on KL001
      derivatives that induce a rhythm-changing activity along with the components that
      trigger opposite modes of action. The first period-shortening molecules that
      target the cryptochrome (CRY) were thus discovered. Detailed studies on the
      effects of these compounds on CRY stability implicate the existence of an as yet
      undiscovered regulatory mechanism.

PMID- 25960184
TI  - Dissociation between diurnal cycles in locomotor activity, feeding behavior and
      hepatic PERIOD2 expression in chronic alcohol-fed mice.
AB  - Chronic alcohol consumption contributes to fatty liver disease. Our studies
      revealed that the hepatic circadian clock is disturbed in alcohol-induced hepatic
      steatosis, and effects of chronic alcohol administration upon the clock itself
      may contribute to steatosis. We extended these findings to explore the effects of
      chronic alcohol treatment on daily feeding and locomotor activity patterns. Mice
      were chronically pair-fed ad libitum for 4 weeks using the Lieber-DeCarli liquid
      diet, with calorie-controlled liquid and standard chow diets as control groups.
      Locomotor activity, feeding activity, and real-time bioluminescence recording of
      PERIOD2::LUCIFERASE expression in tissue explants were measured. Mice on liquid
      control and chow diets exhibited normal profiles of locomotor activity, with a
      ratio of 22:78% day/night activity and a peak during early night. This pattern
      was dramatically altered in alcohol-fed mice, marked by a 49:51% ratio and the
      absence of a distinct peak. While chow-diet fed mice had a normal 24:76% ratio of
      feeding activity, with a peak in the early night, this pattern was dramatically
      altered in both liquid-diet groups: mice had a 43:57% ratio, and an absence of a
      distinct peak. Temporal differences were also observed between the two liquid
      diet groups during late day. Cosinor analysis revealed a ~4-h and ~6-h shift in
      the alcohol-fed group feeding and locomotor activity rhythms, respectively.
      Analysis of hepatic PER2 expression revealed that the molecular clock in alcohol
      fed and control liquid-diet mice was shifted by ~11 h and ~6 h, respectively. No
      differences were observed in suprachiasmatic nucleus explants, suggesting that
      changes in circadian phase in the liver were generated independently from the
      central clock. These results suggest that chronic alcohol consumption and a
      liquid diet can differentially modulate the daily rhythmicity of locomotor and
      feeding behaviors, aspects that might contribute to disturbances in the circadian
      timing system and development of hepatic steatosis.

PMID- 25960186
TI  - Interaction of PEGylated anti-hypertensive drugs, amlodipine, atenolol and
      lisinopril with lipid bilayer membrane: A molecular dynamics simulation study.
AB  - The interaction of PEGylated anti-hypertensive drugs, amlodipine, atenolol and
      lisinopril with lipid bilayer membrane dimyristoylphosphatidylcholine (DMPC) has
      been studied in nine different simulation systems consisting of 128 lipid
      molecules and appropriate number of water molecules by molecular dynamics method
      and by utilizing GROMACS software. The influences of PEGylation on the mentioned
      drugs and the differences in application of two types of spacer molecules on the
      performance of drugs and DMPC membrane have been evaluated and mass density of
      the components in the simulation box, mean square displacement (MSD),
      electrostatic potential, hydrogen bonding, radial distribution function (RDF),
      area per lipid, order parameter, and angle distribution of the component
      molecules including drug, DMPC and PEG has been investigated. Furthermore,
      umbrella sampling analysis indicated that, PEGylation of the drugs made
      amlodipine to behave more hydrophilic, whereas in case of lisinopril and
      atenolol, PEGylation made these drugs to behave more hydrophobic. In almost all
      of the simulated systems, PEGylation increased the diffusion coefficient of the
      drugs. 

PMID- 25960187
TI  - Myeloid sarcoma as the initial presentation of chronic myelogenous leukemia,
      medullary chronic phase in era of tyrosine kinase inhibitors: A report of 11
      cases.

PMID- 25960189
TI  - Folic acid supplementation in vitro induces cell type-specific changes in BRCA1
      and BRCA 2 mRNA expression, but does not alter DNA methylation of their promoters
      or DNA repair.
AB  - Dietary supplementation with folic acid (FA) has been shown to induce opposing
      effects on cancer-related outcomes. The mechanism underlying such heterogeneity
      is unclear. We hypothesized that FA supplementation induces changes in breast
      cancer-associated (BRCA) genes 1 and 2 expression and function through altered
      epigenetic regulation in a cell type-dependent manner. We investigated the effect
      of treating normal and cancer cells with physiologically relevant FA
      concentrations on the mRNA and protein expression, capacity for DNA repair, and
      DNA methylation of BRCA1 and BRCA2. FA treatment induced dose-related increases
      in BRCA1 mRNA expression in HepG2, Huh-7D12, Hs578T, and JURKAT and in BRCA2 in
      HepG2, Hs578T, MCF7, and MDA-MB-157 cells. FA did not affect the corresponding
      normal cells or on any of the ovarian cell lines. Folic acid induced increased
      BRCA1 protein expression in Hs578T, but not HepG2 cells, whereas BRCA2 protein
      levels were undetectable. FA treatment did not alter DNA repair in liver-derived
      cells, whereas there were transient effects on breast-derived cells. There was no
      effect of FA treatment on BRCA1 or BRCA2 DNA methylation, although there was some
      variation in the methylation of specific CpG loci between some cell lines.
      Overall, these findings show that the effects of FA on BRCA-related outcomes
      differ between cells lines, but the biological consequences of induced changes in
      BRCA expression appear to be at most limited. 

PMID- 25960188
TI  - The ecological forecast horizon, and examples of its uses and determinants.
AB  - Forecasts of ecological dynamics in changing environments are increasingly
      important, and are available for a plethora of variables, such as species
      abundance and distribution, community structure and ecosystem processes. There
      is, however, a general absence of knowledge about how far into the future, or
      other dimensions (space, temperature, phylogenetic distance), useful ecological
      forecasts can be made, and about how features of ecological systems relate to
      these distances. The ecological forecast horizon is the dimensional distance for
      which useful forecasts can be made. Five case studies illustrate the influence of
      various sources of uncertainty (e.g. parameter uncertainty, environmental
      variation, demographic stochasticity and evolution), level of ecological
      organisation (e.g. population or community), and organismal properties (e.g. body
      size or number of trophic links) on temporal, spatial and phylogenetic forecast
      horizons. Insights from these case studies demonstrate that the ecological
      forecast horizon is a flexible and powerful tool for researching and
      communicating ecological predictability. It also has potential for motivating and
      guiding agenda setting for ecological forecasting research and development. 

PMID- 25960190
TI  - Cyclic Group 15 Radical Cations.
AB  - Singlet cyclo-1,3-dipnicta-2,4-diazane-1,3-diyls of the type [E(MU-NTer)2 E] (2,
      E=P, As, Ter=2,6-dimesitylphenyl) can undergo a one-electron-oxidation utilizing
      silver salts of weakly coordinating anions such as [AgLn][B(C6F5)4 ] (L=donor
      solvents) to afford the novel cyclic radical cations, [E(MU-NTer)2E](+.) (3(+.)).
      When smaller and more basic anions were employed in the reaction, the anions were
      found to form covalent bonds to the radical centers yielding dipnictadiazanes,
      [FP(MU-NTer)2PF] (5) and [(CF3CO2)P(MU-NTer)2P(CF3CO2)] (6). A two-electron
      oxidation process, resulting in the formation of dications of the type [E(MU
      NTer)2E](2+), could not be observed. Computational and EPR data revealed that the
      spin density is almost completely localized at the two heavier pnictogen centers
      E of the former 1,3-dipnictadiazane-1,3-diyls. The bonding situation in the
      radical cations features a rare example of a transannular one-electron pi bond
      without having a sigma bond.

PMID- 25960191
TI  - Landscape of protein domain interactome.

PMID- 25960192
TI  - Impact of ethnicity and race on response to Angiotensin-converting enzyme
      inhibitors in heart failure.

PMID- 25960193
TI  - Growth mixture modeling: the new statistical kid on the block?

PMID- 25960194
TI  - Hemispheric alpha asymmetry and self-rated originality of ideas.
AB  - The generation of highly original ideas in divergent thinking tasks has been
      found to be associated with task-related changes in the alpha band. The goal of
      the current study was to determine if exposure to brainwave entrainment (BWE) at
      the alpha centre frequency before and during performance of a divergent thinking
      task would result in increases in task-related, event-related synchrony and the
      production of more highly original ideas. We found that alpha entrainment
      interfered with the oscillatory dynamics associated with divergent thinking such
      that only the control group showed greater right hemispheric engagement.
      Furthermore, the control group showed greater self-rated originality. These
      findings provide confirmation of the importance of hemispheric asymmetry in alpha
      power to successful divergent thinking and indicate that refinements are required
      in order for BWE to be used effectively to improve divergent thinking
      performance. 

PMID- 25960196
TI  - Type I interferon and T helper 17 cells co-exist and co-regulate disease
      pathogenesis in lupus patients.
AB  - AIM: T-helper 17 cells (Th17) and type I interferon (IFN-I) play a critical role
      in the pathogenesis of systemic lupus erythematosus (SLE). Previous studies have
      suggested that IFN-I suppresses Th17 development under autoimmune settings.
      Therefore, the main objective of this study was to define the association between
      IFN-I and Th17 pathways in SLE. METHODS: Peripheral blood samples and disease
      activity measures were collected from 31 patients fulfilling the American College
      of Rheumatology revised criteria for SLE. Serum was evaluated for IFN-alpha
      bioactivity and interleukin (IL)-6 levels by cell-based bioluminescence assay and
      enzyme-linked immunosorbent assay, respectively. The frequency of Th17 cells in
      peripheral blood was determined by intracellular cytokine staining for IL-17.
      RESULTS: IFN-alpha bioactivity in the serum of lupus subjects (mean +/- SD: 6.510
      +/- 3.686) was significantly higher (P = 0.001) compared to healthy controls (2.9
      +/- 1.061). Additionally, 58.1% and 41.9% of SLE subjects displayed high and low
      IFN-alpha bioactivity, respectively. We observed a significant increase (P =
      0.04) in the percentage of Th17 cells in lupus subjects with high IFN-alpha
      bioactivity (1.9 +/- 1.0) compared to lupus subjects with low IFN-alpha
      bioactivity (1.2 +/- 0.9). Lupus subjects with high IFN-alpha bioactivity and
      Th17 cells had significantly higher disease activity (P = 0.04) and serum IL-6
      levels (P = 0.01) compared to patients with low IFN-alpha activity and low Th17
      cells. CONCLUSION: Type I interferon and Th17 pathways co-exist and co-regulate
      the pathogenic processes in SLE. Additionally, these studies clearly identify IL
      6 as a common link between IFN-I and Th17 pathways in SLE pathogenesis.

PMID- 25960195
TI  - Non-autonomous DAF-16/FOXO activity antagonizes age-related loss of C. elegans
      germline stem/progenitor cells.
AB  - Stem cells maintain tissues and organs over the lifespan of individuals. How
      aging influences this process is unclear. Here we investigate the effects of
      aging on C. elegans germline stem/progenitor cells and show that the progenitor
      pool is depleted over time in a manner dependent on inhibition of DAF-16/FOXO by
      insulin/IGF-1 signalling (IIS). Our data indicate that DAF-16/FOXO activity in
      certain somatic gonad cells is required for germline progenitor maintenance, and
      that this role is separable from the effect of DAF-16/FOXO on organismal aging.
      In addition, blocking germ cell flux, similar to reducing IIS, maintains germline
      progenitors. This effect is partially dependent on gonadal DAF-16/FOXO activity.
      Our results imply that (1) longevity pathways can regulate aging stem cells
      through anatomically separable mechanisms, (2) stem cell maintenance is not
      necessarily prioritized and (3) stem cell regulation can occur at the level of an
      entire organ system such as the reproductive system. 

PMID- 25960197
TI  - Molecular mechanism for USP7-mediated DNMT1 stabilization by acetylation.
AB  - DNMT1 is an important epigenetic regulator that plays a key role in the
      maintenance of DNA methylation. Here we determined the crystal structure of DNMT1
      in complex with USP7 at 2.9 A resolution. The interaction between the two
      proteins is primarily mediated by an acidic pocket in USP7 and Lysine residues
      within DNMT1's KG linker. This intermolecular interaction is required for USP7
      mediated stabilization of DNMT1. Acetylation of the KG linker Lysine residues
      impair DNMT1-USP7 interaction and promote the degradation of DNMT1. Treatment
      with HDAC inhibitors results in an increase in acetylated DNMT1 and decreased
      total DNMT1 protein. This negative correlation is observed in differentiated
      neuronal cells and pancreatic cancer cells. Our studies reveal that USP7-mediated
      stabilization of DNMT1 is regulated by acetylation and provide a structural basis
      for the design of inhibitors, targeting the DNMT1-USP7 interaction surface for
      therapeutic applications.

PMID- 25960198
TI  - A perfect storm: How tumor biology, genomics, and health care delivery patterns
      collide to create a racial survival disparity in breast cancer and proposed
      interventions for change.
AB  - It is well known that there is a significant racial divide in breast cancer
      incidence and mortality rates. African American women are less likely to be
      diagnosed with breast cancer than white women but are more likely to die from it.
      This review explores the factors that may contribute to the racial survival
      disparity. Consideration is paid to what is known about the role of differences
      in tumor biology, genomics, cancer screening, and quality of cancer care. It is
      argued that it is the collision of 2 forces, tumor biology and genomics, with
      patterns of care that leads to the breast cancer mortality gap. The delays,
      misuse, and underuse of treatment for African American patients are of increased
      significance when these patients are presenting with more aggressive forms of
      breast cancer. In the current climate of health care reform ushered in by the
      Affordable Care Act, this article also evaluates interventions to close the
      disparity gap. Prior interventions have been too narrowly focused on the patient
      rather than addressing the system and improving care across the continuum of
      breast cancer evaluation and treatment. Lastly, areas of future investigation and
      policy initiatives aimed at reducing the racial survival disparity in breast
      cancer are discussed.

PMID- 25960201
TI  - Estimation of the uncertainty of analyte concentration from the measurement
      uncertainty.
AB  - Ligand-binding assays, such as immunoassays, are usually analysed using standard
      curves based on the four-parameter and five-parameter logistic models. An
      estimate of the uncertainty of an analyte concentration obtained from such curves
      is needed for confidence intervals or precision profiles. Using a numerical
      simulation approach, it is shown that the uncertainty of the analyte
      concentration estimate becomes significant at the extremes of the concentration
      range and that this is affected significantly by the steepness of the standard
      curve. We also provide expressions for the coefficient of variation of the
      analyte concentration estimate from which confidence intervals and the precision
      profile can be obtained. Using three examples, we show that the expressions
      perform well. 

PMID- 25960200
TI  - Insecticide resistance status of Myzus persicae in Greece: long-term surveys and
      new diagnostics for resistance mechanisms.
AB  - BACKGROUND: Myzus persicae nicotianae is an important pest in Greece, controlled
      mainly by neonicotinoids. Monitoring of the aphid populations for resistance
      mechanisms is essential for effective control. RESULTS: Two new RFLP-based
      diagnostics for the detection of the M918T (super-kdr pyrethroid resistance) and
      nAChR R81T (neonicotinoid resistance) mutations were applied, along with other
      established assays, on 131 nicotianae multilocus genotypes (MLGs) collected from
      tobacco and peach in Greece in 2012-2013. Furthermore, we present resistance data
      from aphid clones (>500, mainly nicotianae) collected in 2006-2007. About half of
      the clones tested with a diagnostic dose of imidacloprid were tolerant. The R81T
      mutation was not found in the 131 MLGs and 152 clones examined. Over half (58.6%)
      of a subset of 29 clones showed a 9-36-fold overexpression of CYP6CY3. M918T was
      found at low to moderate frequencies. The kdr and MACE mechanisms and
      carboxylesterase-based resistance were found at high frequency in all years.
      CONCLUSION: The aphid retains costly resistance mechanisms even in the absence of
      pressure from certain insecticides, which could be attributed to factors related
      to climate and genetic properties of the populations. The indication of build-up
      of resistance/tolerance to neonicotinoids, related to CYP6CY3 overexpression, is
      a matter of concern. (c) 2015 Society of Chemical Industry.

PMID- 25960203
TI  - The excited state antiaromatic benzene ring: a molecular Mr Hyde?
AB  - The antiaromatic character of benzene in its first pipi* excited triplet state
      (T1) was deduced more than four decades ago by Baird using perturbation molecular
      orbital (PMO) theory [J. Am. Chem. Soc. 1972, 94, 4941], and since then it has
      been confirmed through a range of high-level quantum chemical calculations. With
      focus on benzene we now first review theoretical and computational studies that
      examine and confirm Baird's rule on reversal in the electron count for
      aromaticity and antiaromaticity of annulenes in their lowest triplet states as
      compared to Huckel's rule for the ground state (S0). We also note that the rule
      according to quantum chemical calculations can be extended to the lowest singlet
      excited state (S1) of benzene. Importantly, Baird, as well as Aihara [Bull. Chem.
      Soc. Jpn. 1978, 51, 1788], early put forth that the destabilization and excited
      state antiaromaticity of the benzene ring should be reflected in its
      photochemical reactivity, yet, today these conclusions are often overlooked.
      Thus, in the second part of the article we review photochemical reactions of a
      series of benzene derivatives that to various extents should stem from the
      excited state antiaromatic character of the benzene ring. We argue that benzene
      can be viewed as a molecular "Dr Jekyll and Mr Hyde" with its largely unknown
      excited state antiaromaticity representing its "Mr Hyde" character. The
      recognition of the "Jekyll and Hyde" split personality feature of the benzene
      ring can likely be useful in a range of different areas. 

PMID- 25960204
TI  - Chemically-induced TLE models: Topical application.
AB  - Epilepsy is a condition of the brain that occurs in many different forms. For
      obvious reasons, understanding the complex mechanisms underlying the process of
      epileptogenesis cannot be fully acquired in clinical studies or analyses of
      surgically resected human epileptic specimens. Accordingly, a variety of animal
      models have been developed that recapitulate different aspects of the various
      forms of epilepsies. In our review we mainly focus on those chemically induced
      models that recapitulate characteristics typically seen in human temporal lobe
      epilepsies. By comparing models based on topical application of different agents,
      advantages and disadvantages are discussed with respect to parameters including
      reliability and mortality, as well as the similarity with the human condition of
      functional and morphological alterations occurring in different brain regions in
      the course of epileptogenesis and in the chronic state. 

PMID- 25960205
TI  - Organogenesis: variations on a theme.

PMID- 25960206
TI  - NFkB is activated by multiple mechanisms in hairy cell leukemia.
AB  - Hairy cell leukemia (HCL) is a rare chronic B-cell lymphoproliferative disorder
      of unclear pathogenesis. Recent studies have identified BRAF(V600E) mutations in
      most HCL patients, highlighting this abnormality as a molecular hallmark for this
      disease. Cell lines originating from HCL patients lack BRAF mutations but retain
      the typical piliferous morphology and the distinctive HCL immunophenotype, thus,
      constituting suitable tools for identifying alternative tumor genes and leukemic
      mechanisms in this malignancy. To this end, we integrated genomic and
      transcriptional profiling of the HCL cell line MLMA. The expression levels of
      genomically targeted genes were compared to four HCL control cell lines, thus,
      identifying 91 chromosomally deregulated genes. Gene set enrichment analysis of
      these indicted apoptosis, proliferation, and DNA damage response as altered
      processes. Accordingly, prominent target genes overexpressed in this cell line
      include ATM, BRAF, CDK6, CUTL1/CUX1, H2AFX, and REL. Treatment of MLMA with
      selective pharmacological inhibitors and specific siRNA-mediated gene knockdowns
      highlighted a central role for NFkB in their deregulation in HCL. Moreover,
      relevant expression profiling data from HCL and ABC-DLBCL cell lines display
      elevated NFkB-pathway activity when compared to GC-DLBCL equivalents. Finally,
      analysis of HCL patient samples in silico collectively supported the clinical
      significance of NFkB activation in this disease. In conclusion, we identified
      deregulated genes and multiple mechanisms underlying aberrantly activated NFkB
      pathway in HCL. Therefore, NFkB may represent a B-cell specific hallmark of HCL
      and a promising novel therapeutic target, most notably in patients lacking BRAF
      mutations in this entity including variant HCL.

PMID- 25960207
TI  - Effects of miRNA-197 overexpression on proliferation, apoptosis and migration in
      levonorgestrel treated uterine leiomyoma cells.
AB  - BACKGROUND/AIMS: Uterine leiomyoma is the ahead benign tumor of the female
      genital tract, which resulted in menstrual abnormalities, recurrent pregnancy
      loss, and other serious gynecological disorders in women. Recently, as the
      process of exploring the brief molecular mechanisms of tumorgenesis, microRNAs
      (miRNAs) have attracted much more attention. METHODS: In this study, we first
      confirmed that microRNA-197 (miR-197) was down-regulated significantly in human
      uterus leiomyoma by quantity real-time polymerase chain reaction, compared to
      normal uterus myometrium. Then we observed the potential effects of miR-197
      overexpression on human uterus leiomyoma cells by cell counting kit 8, wound
      healing assay, and flow cytometric assessment separately. RESULTS: The data
      showed that miR-197 could inhibit cell proliferation, induce cell apoptosis, and
      block cell migration in vitro. Coincidently, levonorgestrel (LNG), a well-known
      uterus leiomyoma therapy, could induce miR-197 expression in human uterus
      leiomyoma cells, and over-expression of miR-197 showed a synergy effect on human
      uterus leiomyoma cell proliferation and apoptosis with LNG. CONCLUSION: In this
      study, the data showed that miR-197 could play an anti-oncogenic role in human
      uterus leiomyoma cells, and cooperate with LNG on the cell proliferation and
      apoptosis, which suggested that miR-197 might be a potential target and provided
      database for clinical treatment.

PMID- 25960208
TI  - miR-25 promotes glioma cell proliferation by targeting CDKN1C.
AB  - MicroRNAs (miRNA) have oncogenic or tumor-suppressive roles in the development
      and growth of human glioma. Glioma development is also associated with alteration
      in the activities and expression of cell cycle regulators, and miRNAs are
      emerging as important regulators of cell cycle progression. Here, we show that
      miR-25 is overexpressed in 91% of examined human glioma tissues and 4 out of 6
      human glioma cell lines. MiR-25 increases cell proliferation in two independent
      glioma cell lines. Ectopic expression of miR-25 was found to reduce CDKN1C
      protein levels by directly targeting its 3'-untranslated region (UTR). Notably,
      ablation of endogenous miR-25 rescued CDKN1C expression and significantly
      decreased glioma cell proliferation by facilitating normal cell cycle
      progression. Our clinical investigation found CDKN1C and miR-25 levels were
      inversely correlated. Lastly, downregulation of CDKN1 by siRNA blocked the
      activity of miR-25 on promoting glioma cell proliferation. Overall, our results
      for the first time show an oncogenic role of miR-25 in human glioma by targeting
      CDKN1C and that miR-25 could potentially be a therapeutic target for glioma
      intervention. 

PMID- 25960209
TI  - Cerebral ischemia-induced mitochondrial changes in a global ischemic rat model by
      AFM.
AB  - Mitochondria play a central role in cell survival, and apoptotic cell death is
      associated with morphological changes in mitochondria. Quantification of the
      morphological and mechanical property changes in brain mitochondria is useful for
      evaluating the degree of ischemic injury and the neuroprotective effects of
      various drugs. This study was performed to investigate the changes in brain
      mitochondria in an 11-vessel occlusion ischemic model treated with magnesium
      sulfate (MgSO4), utilizing atomic force microscopy (AFM). Rats were randomly
      divided into three groups consisting of sham (n=6), global ischemia (GI, n=6),
      and MgSO4-treated global ischemia (MgSO4, n=6). The biophysical properties of
      brain mitochondria determined from AFM topographic images and adhesion force from
      force-distance measurements. The mean perimeter of ischemic mitochondria
      significantly increased to 2,396+/-541 nm (vs. 1,006+/-318 nm in control group,
      P<0.001). The MgSO4 treatment during global ischemia reduced the perimeter of
      ischemic mitochondria (1,127+/-399 nm, P<0.001). The other parameters including
      length, width and area were significantly different than the GI group. Besides,
      the adhesion force (23.2+/-3.9 nN) of isolated mitochondria from the MgSO4 group
      was close to normal levels (28.5+/-2.5 nN), compared with that of ischemic ones
      (17.7+/-3.3 nN, P<0.001). To confirm the neuroprotective effects of MgSO4, we
      performed Nissl staining. This study suggested that quantitative analysis of
      mitochondrial changes utilizing AFM could be effective for evaluating neuronal
      injury and drug effects.

PMID- 25960210
TI  - Development of thalidomide-loaded biodegradable devices and evaluation of the
      effect on inhibition of inflammation and angiogenesis after subcutaneous
      application.
AB  - PURPOSE: To develop thalidomide-loaded poly-lactide-co-glycolide implants and
      evaluate its in vivo release and biological activity against inflammation and
      angiogenesis after subcutaneous administration. METHODS: Implants were prepared
      by the hot molding technique and characterized using stereomicroscopy, thermal
      analysis and X-ray diffraction. Swiss mice, divided in groups 1-3, received a
      subcutaneous implant containing 25% (w/w), 50% (w/w) or 75% (w/w) of thalidomide,
      respectively (n=6). The drug levels were determined during a 28-day study period.
      The toxicity associated with the implants was evaluated by light microscopy. The
      potential of the developed implant in the inhibition of inflammation and
      angiogenesis was evaluated in vivo using the sponge model. RESULTS: Thalidomide
      implant was developed and its characterization proved the stability of the drug
      and the polymer during preparation. Release profiles in vivo demonstrated an
      extended release of thalidomide from the implants during the 28 days.
      Histological evaluation did not show any sign of intense local inflammatory
      response to the presence of the implants in the subcutaneous pouch. The
      thalidomide implant reduced the number of vessels and N-acetyl-b-glucosaminidase
      (NAG) in vivo. CONCLUSION: The biodegradable implants delivered safe doses of
      thalidomide that were also effective to induce angiogenesis and inflammation
      regression.

PMID- 25960211
TI  - Interferon should be used to prevent and/or treat Ebola virus disease.

PMID- 25960212
TI  - Oxidative modification induced by photodynamic therapy with Photofrin(r)II and 2
      methoxyestradiol in human ovarian clear carcinoma (OvBH-1) and human breast
      adenocarcinoma (MCF-7) cells.
AB  - Ovarian cancer is among the most lethal cancers in women. The successful
      anticancer treatment depends on the effectiveness of cytotoxic effect of applied
      therapeutic procedures either alone or in combination with other treatments.
      Photodynamic therapy (PDT) is a relatively new method of anticancer therapy. Its
      dominant mechanism of action is the over-production of reactive oxygen species
      induced by oxidative stress in malignant cells, which attack lipid membranes,
      proteins and nucleic acids. One of the important mechanisms is induction of
      unfolded protein response, ubiquitin-proteasome pathway of protein degradation.
      The aim of this study was to evaluate the cytotoxic effect of various protective
      enzymes in ovarian carcinoma clear cell line in comparison to the model breast
      cell line after photodynamic reaction and photodynamic reaction with 2
      methoxyestradiol (2-Me). Human malignant ovarian cell line (OvBH-1) was used and
      human breast adenocarcinoma cells (MCF-7) were used as a control. Photodynamic
      reaction (PDR) with Photofrin((r))II and Ph((r))II with 2-Me was performed. The
      expression of protective proteins by immunocytochemistry (HSP70 and iNOS) and
      western blot (Hsp27 and Hsp70) methods was evaluated directly, 3 and 6 h after
      PDR. The changes in cells' cytoskeleton were evaluated using immunofluorescence
      by confocal microscopy. The expression of iNOS was observed for both experiments
      with differential intensity and quantity. A higher expression of Hsp70 in MCF-7
      cells was observed than in OvBh-1 cells. The reorganization of cytoskeleton and
      nucleus was observed after 3 and 6 h after exposition to light.

PMID- 25960213
TI  - Homology modelling and molecular docking of MDR1 with chemotherapeutic agents in
      non-small cell lung cancer.
AB  - MDR1, a protein commonly involved in drug transport, has been linked to multi
      drug resistance and disease progression in cancers such as non-small cell lung
      cancer. Hence, targeting this protein is essential for improving drug design and
      preventing adverse drug-drug interactions. The aim of the study was to examine
      chemotherapeutic drug binding to MDR1 and the interactions therein. We have used
      Schrodinger suite 2014, to perform homology modelling of human MDR1 based on
      Mouse MDR1, followed by Induced Fit Docking with Paclitaxel, Docetaxel,
      Gemcitabine, Carboplatin and Cisplatin drugs. Finally, we evaluated drug binding
      affinities using Prime/MMGBSA and using these scores we compared the affinities
      of combination therapies against MDR1. Analysis of the docking results showed
      Paclitaxel>Docetaxel>Gemcitabine>Carboplatin>Cisplatin as the order of binding
      affinities, with Paclitaxel having the best docking score. The combination drug
      binding affinity analysis showed Paclitaxel+Gemcitabine to have the best docking
      score and hence, efficacy. Through our investigation we have identified the
      residues Gln 195 and Gln 946 to be more frequently involved in drug binding
      interactions with MDR1. Our results suggest that, Paclitaxel or combination of
      Paclitaxel+Gemcitabine could serve as a suitable therapy against MDR1 in NSCLC
      patients. Thus, our study provides new insight into the possible repurposing of
      chemotherapeutic drugs in targeting elevated MDR1 levels in NSCLC patients,
      thereby ensuring better overall outcome. Further our study highlights the use of
      in silico methodologies in understanding drug binding to protein targets and its
      relevance to advancing lung cancer therapy. 

PMID- 25960214
TI  - Downregulation of the CXCR4/CXCL12 axis blocks the activation of the Wnt/beta
      catenin pathway in human colon cancer cells.
AB  - Chemokine CXCL12 is an extracellular chemokine, which binds to its cell surface
      receptor CXCR4. High expressions of CXCR4 and CXCL12 are associated with
      biological malignant potential in colon cancers. We aimed to investigate the
      roles of the CXCR4/CXCL12 axis in activation of the Wnt/beta-catenin pathway in
      the development of colon cancers. Using colon cancer cell line, we performed the
      RNA interference assay to downregulate the expression of CXCR4. Cells were
      exposed to CXCL12 and their growth and metastatic activity were examined. Matrix
      metalloproteinases (MMPs) activity were analyzed by the gelatin zymography assay.
      Cell migration ability was estimated by assays of scratch wound and transwell
      chamber. The expression of CXCR4 and molecules relevant to the Wnt/beta-catenin
      pathway were analyzed by the western blotting and real-time PCR assays. Human
      colon cancer HT-29 cells identified high expression of CXCR4. HT-29 cells highly
      responded to CXCL12 stimulation, showing the increase of cell proliferation,
      invasion and migration through the Matrigeal. The secretion and activity of MMP-2
      and MMP-9 were also stimulated in HT-29 cells exposure to CXCL12. However, the
      CXCR4 knockdown HT-29 cells did not response to CXCL12 stimulation. We suggested
      that the activation of the CXCR4/CXCL12 axis be blocked in the CXCR4 knockdown
      cells. This study indicated that one key to the role of the CXCR4/CXCL12 axis is
      activation of the Wnt/beta-catenin pathway. Downregulation of the CXCR4/CXCL12
      axis thus reduces cancer growth and metastasis. Targeted therapy utilizing the
      CXCR4/CXCL12 axis could be an effective strategy for treatment of colon cancers. 

PMID- 25960215
TI  - miR-194 regulated AGK and inhibited cell proliferation of oral squamous cell
      carcinoma by reducing PI3K-Akt-FoxO3a signaling.
AB  - Growing evidence supports that microRNAs (miRNAs) play crucial roles in cancer
      progression by directly downregulating multiple targets. However, the underlying
      mechanisms of miRNAs in oral squamous cell carcinoma (OSCC) are poorly
      understood. In the current study, we found that miR-194 expression was markedly
      downregulated in both clinical OSCC tissues and OSCC cell lines, compared with
      adjacent non-cancerous tissues and normal tongue epithelial cell TEC,
      respectively. Overexpression of miR-194 suppressed, whereas miR-194-in promoted
      OSCC cell proliferation. Furthermore, we demonstrated that miR-194 could reduce
      the phosphoinositide 3-kinase (PI3K)/AKT/FoxO3a signaling pathway by suppressing
      acylglycerol kinase (AGK) directly, resulting in decreasing cyclin D1 expression
      and increasing expression of p21 in OSCC. In sum, our data provide compelling
      evidence that miR-194 functions as a potential tumor suppressor by inhibiting the
      PI3K/AKT/FoxO3a signaling pathway and might sever as a potential therapeutic
      target for OSCC patients. 

PMID- 25960216
TI  - The microRNA-217 functions as a tumor suppressor and is frequently downregulated
      in human osteosarcoma.
AB  - OBJECTIVE: Dysregulation of miRNA is always associated with cancer development
      and progression. Aberrant expression of miR-217 has been found in some types of
      cancer. However, its expression and function in osteosarcoma remain unclear. The
      aim of this study was to explore the effects of miR-217 in osteosarcoma
      tumorigenesis and development. METHODS: The expression level of miR-217 was
      quantified by real-time RT-PCR in human osteosarcoma cell lines and tissues. MTT,
      flow cytometric, transwell invasion and migration assays, and tumorigenicity in
      vivo were adopted to observe the effects of miR-217 on MG-63 cell phenotypes.
      RESULTS: MiR-217 was significantly downregulated in osteosarcoma cell lines and
      clinical specimens. Decreased miR-217 expression was significantly associated
      with large tumor size, positive distant metastasis, and advanced clinical stage.
      Low miR-217 expression in osteosarcoma was an independent predictor of poor
      survival. Overexpression of miR-217 can inhibit the proliferation, invasion,
      migration and promoted apoptosis of MG-63 cells in vitro and in vivo.
      CONCLUSIONS: These findings indicate that miR-217 may act as a tumor suppressor
      in osteosarcoma and would serve as a novel therapeutic agent for miRNA-based
      therapy.

PMID- 25960217
TI  - MiR-939 promotes the proliferation of human ovarian cancer cells by repressing
      APC2 expression.
AB  - Aberrant activation of the Wnt/beta-catenin signal pathway is frequently observed
      in various human cancers. Therefore, it was speculated that adenomatous polyposis
      coli 2 (APC2) could play important roles in activating the Wnt/beta-catenin
      pathway. In this present study, miR-939 expression was markedly upregulated in
      ovarian cancer tissues and ovarian cancer cells. In functional assays,
      Overexpression of miR-939 promoted the proliferation and anchorage-independent
      growth of ovarian cancer cells, whereas inhibition of miR-939 inhibited this
      effect. Bioinformatics analysis further revealed APC2, a putative tumor
      suppressor as a potential target of miR-939. Result of luciferase reporter assays
      showed that miR-939 directly binds to the 3'-untranslated region (3'-UTR) of APC2
      mRNA. Furthermore, we demonstrated that miR-939 could reduce the Wnt/beta-catenin
      signal pathway by suppressing APC2 directly, resulting in increasing expression
      of CyclinD1, MYC and TCF. In functional assays, APC2-silenced in miR-939-in
      transfected ES-2 cells have positive effect to promote cell proliferation,
      suggesting that direct APC2 downregulation is required for miR-939-induced
      ovarian cancer cell proliferation. In sum, our data provided compelling evidence
      that miR-939 functioned as a potential tumor promoter by regulating the Wnt/beta
      catenin signal pathway through direct suppression of APC2 expression and might
      sever as a potential therapeutic target for ovarian cancer patients. 

PMID- 25960218
TI  - A novel class I histone deacetylase inhibitor, I-7ab, induces apoptosis and
      arrests cell cycle progression in human colorectal cancer cells.
AB  - Epigenetic mutations are closely associated with human diseases, especially
      cancers. Among them, dysregulations of histone deacetylases (HDACs) are commonly
      observed in human cancers. Recent years, HDAC inhibitors have been identified as
      promising anticancer agents; several HDAC inhibitors have been applied in
      clinical practice. In this study, we synthesized a novel N-hydroxyacrylamide
      derived HDAC inhibitor, I-7ab, and examined its antitumor activity. Our
      investigations demonstrated that I-7ab exerted cytotoxicity toward and inhibited
      the growth of human cancer cell lines at micromolar concentrations. Among tested
      cells, HCT116 was the most sensitive one to the treatment of I-7ab. However, I
      7ab displayed far less cytotoxicity in human normal cells. In HCT116 cells, I-7ab
      inhibited the expression of class I HDACs, especially that of HDAC3, and
      suppressed EGFR signaling pathway. With respect to the cytotoxic effect of I-7ab,
      it induced apoptosis via increasing the Bax/Bcl-2 ratio and suppressing the
      translocation of NF-kappaB. Other than inducing apoptosis, I-7ab inhibited the
      expression of cyclin B1 and thereby arrests cell cycle progression at G2/M phase.
      Further analyses revealed potential role of p53 and p21 in I-7ab-induced
      apoptosis and cell cycle arrest. According to our findings, I-7ab may serve as a
      lead compound for potential antitumor drugs. 

PMID- 25960219
TI  - Up-regulation of BRAF activated non-coding RNA is associated with radiation
      therapy for lung cancer.
AB  - Radiation therapy has become more effective in treating primary tumors, such as
      lung cancer. Recent evidence suggested that BRAF activated non-coding RNAs
      (BANCR) play a critical role in cellular processes and are found to be
      dysregulated in a variety of cancers. The clinical significance of BANCR in
      radiation therapy, and its molecular mechanisms controlling tumor growth are
      unclear. In the present study, C57BL/6 mice were inoculated Lewis lung cancer
      cells and exposed to radiation therapy, then BANCR expression was analyzed using
      qPCR. Chromatin immunoprecipitation and western blot were performed to calculate
      the enrichment of histone acetylation and HDAC3 protein levels in Lewis lung
      cancer cells, respectively. MTT assay was used to evaluate the effects of BANCR
      on Lewis lung cancer cell viability. Finally, we found that BANCR expression was
      significantly increased in C57BL/6 mice receiving radiation therapy (P<0.05)
      compared with control group. Additionally, knockdown of BANCR expression was
      associated with larger tumor size in C57BL/6 mice inoculated Lewis lung cancer
      cells. Histone deacetylation was observed to involve in the regulation of BANCR
      in Lewis lung cancer cells. Moreover, over expression HDAC3 reversed the effect
      of rays on BANCR expression. MTT assay showed that knockdown of BANCR expression
      promoted cell viability surviving from radiation. In conclusion, these findings
      indicated that radiation therapy was an effective treatment for lung cancer, and
      it may exert function through up-regulation BANCR expression. 

PMID- 25960220
TI  - CRKL knockdown promotes in vitro proliferation, migration and invasion, in vivo
      tumor malignancy and lymph node metastasis of murine hepatocarcinoma Hca-P cells.
AB  - Our previous study (Biomed Pharmacother 2015;69:11) demonstrated that the over
      expression of CRKL, a chicken tumor virus number 10 regulator of kinase-like
      protein, suppresses in vitro proliferation, invasion and migration of murine
      hepatocarcinoma Hca-P cell, a murine HCC cell with lymph node metastatic (LNM)
      rate of ~25%. In current work, we investigated the effects of CRKL knockdown on
      the in vitro cell proliferation, migration and invasion, and on the in vivo tumor
      malignancy and LNM rate and level for Hca-P cells. Western blotting assay
      indicated that CRKL was down-regulated by ~90% in a monoclonal CrkL-shRNA
      transfected Hca-P cells. Compared with Hca-P and unrelated-shRNA-transfected Hca
      P cell, the in vitro proliferation, migration and invasion potentials were
      significantly enhanced following CRKL stable deregulation. CRKL knock-down
      significantly promoted the tumorigenicity malignancy, LNM rates and level of Hca
      P-transplanted mice. Consistent with our previous work, it can be concluded CRKL
      plays an important role in hepatocarcinoma cell proliferation, invasion and
      migration as well hepatocarcinoma malignancy and metastasis. It functions as a
      potential tumor suppressor in hepatocarcinoma. 

PMID- 25960221
TI  - Anti-fibrotic effect of trans-resveratrol on pancreatic stellate cells.
AB  - Trans-resveratrol, also known as 3,5,4'-trihydroxy-trans-stilbene, is a natural
      stilbenoid found at high concentration in skins of red grapes and berries. Over
      the recent years, it has been reported with a variety of beneficial effects such
      as antioxidant, anti-aging and anti-inflammatory bioactivities; thus often
      utilized as an active substance in human and veterinary therapeutics. In the
      current study, we aimed to delineate the mechanism of its anti-fibrotic action by
      means of various biochemical assays, such as immunofluorescent staining, real
      time polymerase chain reaction and Western blotting analyses in a cellular model,
      the LTC-14 cells, which retain essential characteristics and morphological
      features of primary pancreatic stellate cells (PSCs). Our results demonstrated
      that the application of trans-resveratrol as low as 10 MUM notably suppressed the
      mRNA and protein levels of different fibrotic mediators namely alpha-smooth
      muscle actin, type I collagen and fibronectin in the LTC-14 cells stimulated with
      transforming growth factor-beta, a well recognized pro-fibrotic inducer.
      Importantly, the mechanism of the anti-fibrotic action of trans-resveratrol was
      associated with a decrease in nuclear factor-kappaB activation and protein kinase
      B phosphorylation. In conclusion, our finding suggests that trans-resveratrol may
      serve as a therapeutic or an adjuvant agent in anti-fibrotic approaches and/or
      PSC-relating pathologies.

PMID- 25960222
TI  - The effect of sodium bicarbonate on cytokine secretion in CKD patients with
      metabolic acidosis.
AB  - The incidence of acidosis increases with the progression of chronic kidney
      disease (CKD). Correction of acidosis by sodium bicarbonate may slow CKD
      deterioration. Inflammation, which is common in CKD, may be related to acidosis.
      Whether the slower rate of GFR decline following the correction of acidosis is
      related to changes in inflammatory markers is unknown. The current study examined
      whether correcting CKD-acidosis affected inflammatory cytokines secretion.
      Thirteen patients with CKD 4-5 and acidosis were tested for cytokines secretion
      from peripheral-blood mononuclear cells at baseline and after one month of oral
      sodium bicarbonate. Following treatment with sodium bicarbonate there was no
      change in weight, blood pressure, serum creatinine, albumin, sodium, calcium,
      phosphate, PTH, hemoglobin and CRP. Serum urea decreased (134+/-10-116+/-8 mg/dl,
      P=0.002), potassium decreased (5.1+/-0.4-4.8+/-0.1 mequiv./l, P=0.064), pH
      increased (7.29+/-0.01-7.33+/-0.01, P=0.008), and serum bicarbonate increased
      (18.6+/-0.4 mequiv./l to 21.3+/-0.3 mequiv./l, P=0.001). The secretion of the
      anti-inflammatory cytokine IL-10 decreased (2.75+/-0.25 ng/ml to 2.29+/-0.21
      ng/ml, P=0.041). There was no significant change in the secretion of the other
      pro-inflammatory and anti-inflammatory cytokines, including IL-1beta, IL-2, IL-6,
      TNFalpha, IFNgamma, IL-1ra. Thus, correcting acidosis in CKD with bicarbonate
      decreases IL-10 secretion. Its significance needs to be further investigated.

PMID- 25960223
TI  - Flavonoids at the pharma-nutrition interface: Is a therapeutic index in demand?
AB  - The consumption of flavonoid-rich foods could have beneficial effects on health.
      However, different classes of flavonoids have different effect on disease risk
      and the relationship between flavonoid intake and risk of disease appeared to be
      non-linear. Furthermore, contrarily to vitamins, there are no symptoms of
      deficiency for flavonoids; therefore, our body treats them like other
      xenobiotics. Therefore, a therapeutic index should be determined. Despite
      flavonoids are at the pharma-nutrition interface, drugs and foods are subject to
      different regulatory frameworks and there is no recommended daily allowance (RDA)
      for flavonoids. Relatively little is known about the efficacy, safety and
      underlying mechanisms of these bioactive compounds, especially when taken in
      concert with drugs. Flavonoids could act both as drugs and pro-drugs with
      pharmacological and toxicological promiscuity. Due to the low bioavailability,
      the gastrointestinal tract could be the primary target of flavonoids and
      metabolites. Different effects have been observed after acute and chronic
      consumption and bioavailability and bioactivity have high inter-individual
      variability. Furthermore, the difficulties in the design and in the
      interpretation of human intervention studies make difficult the establishment of
      a therapeutic index for flavonoids. Probably the concept of 'personalized
      nutrition' previously proposed could be the better approach. However, despite
      more studies are needed in order to establish a therapeutic index for each
      flavonoid subclasses, at the moment RDA of total flavonoids could be between 250
      400 mg/d, respecting the seasonality of food sources.

PMID- 25960224
TI  - Impact of the IGFBP3 A-202C polymorphism on susceptibility and clinicopathologic
      features of breast cancer.
AB  - BACKGROUND: Insulin-like growth factor binding protein 3 (IGFBP3) plays an
      important role in cellular proliferation, differentiation, apoptosis, and mammary
      carcinogenesis. Genetic variations in IGFBP3 have been identified to influence
      the circulating IGFBP3 level. The present study determined the impact of an
      important promoter polymorphism (A-202C, rs2854744) on susceptibility and
      progression of breast cancer in a Chinese population. METHODS: We genotyped the
      IGFBP3 A-202C polymorphism in a case-control study involving 465 breast cancer
      patients and 799 age-matched, cancer-free controls using the TaqMan method.
      Logistic regression was used to assess the genetic association between the
      occurrence and progression of breast cancer. RESULTS: Compared with the wild
      genotype (-202AA), we found a statistically significant increased risk of breast
      cancer associated with the variant genotypes (CC vs. AA: OR=2.00, 95% CI=1.25
      3.21; AC+CC vs. AA: OR=1.34, 95% CI=1.06-1.70). In the stratified analysis, the
      increased risk was more apparent among the subgroups of older subjects (OR=1.70,
      95% CI=1.20-2.42). Furthermore, we found that patients carrying variant genotypes
      (AC+CC) had a significantly greater prevalence of large tumor size (OR=1.72, 95%
      CI=1.13-2.64; P=0.021). CONCLUSION: Our results suggest that the functional
      IGFBP3 A-202C polymorphism may influence the susceptibility and progression of
      breast cancer in the Chinese population.

PMID- 25960227
TI  - The apoptotic pathways in the curcumin analog MHMD-induced lung cancer cell death
      and the essential role of actin polymerization during apoptosis.
AB  - As a mode of cell death, apoptosis could be triggered by the extrinsic, intrinsic
      mitochondrial and intrinsic endoplasmic reticulum pathways and actin
      rearrangement is needed during apoptosis. We previously found that one curcumin
      analog MHMD could induce A549 lung cancer cells apoptosis. But the apoptotic
      pathways and the actin dynamics during apoptosis are not known. Here, we detected
      the activation of caspase-3, -8, -9, -12, PARP and the increase ratio of Bax/Bcl
      2 by western blotting in MHMD-exposed A549 cells. Alternatively, caspases
      inhibitors could lead to the disappearance of MHMD-eliciting nuclei fragmentation
      by Hoechst 33342 staining. Besides, JC-1 and DCFH-DA staining showed the fall of
      mitochondrial membrane potential and the release of ROS. Moreover, wound healing
      assay confirmed the MHMD anti-migration ability, which was much more effective
      than curcumin. Importantly, unlike other anticarcinogenic drugs, MHMD might
      induce the actin polymerization but not depolymerization in the process of A549
      cell apoptosis by phalloidin-FITC staining, which is essential to MHMD-induced
      extrinsic, intrinsic mitochondrial and intrinsic ER pathways of cell apoptosis. 

PMID- 25960226
TI  - Diorganotin (IV) complexes with 4-nitro-N-phthaloyl-glycine: Synthesis,
      characterization, antitumor activity and DNA-binding studies.
AB  - Two novel diorganotin (IV) complexes, based on 4-nitro-N-phthaloyl-glycine (HL),
      namely {4-NO2C6H3(CO)2NCH2COO}2Sn(n-Bu)2 (1) and {4-NO2C6H3(CO)2NCH2COO}2SnMe2
      (2), were synthesized and characterized by elemental analysis, FT-IR, (1)H- and
      (13)C-NMR spectroscopic techniques. In vitro antitumor activities of both
      complexes were evaluated by the 3-(4,5-dimethylthiazoly-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay against three human cancer cell lines:
      HepG-2 (human liver carcinoma), SGC-7901 (human gastric carcinoma) and LS174T
      (human colon carcinoma). Complex 1 exhibited strong antitumor activity with IC50
      values of 1.51+/-0.41, 1.80+/-0.63, and 2.48+/-0.96 MUM, respectively; while
      complex 2 had no obvious effects on the three selected cancer cell lines at high
      concentrations up to 100 MUM. Complex 1-induced apoptosis was further confirmed
      by morphological observations and annexin V-FITC/PI staining flow cytometry
      analysis in HepG-2 cells. Cell cycle analysis revealed that complex 1 caused cell
      cycle arrest at G2/M phase. Molecular mechanism studies suggested that the
      apoptosis was mediated through the mitochondrial pathway with intracellular
      reactive oxygen species (ROS) promotion and mitochondrial membrane potential
      (MMP) disruption by finally activating effector caspase-3/9 to trigger cell
      apoptosis. Moreover, the interactions of both complexes with calf thymus DNA (CT
      DNA) were investigated by using UV-Vis titration and fluorometric competition
      measurements. The DNA-binding constants Kb (intrinsic binding constant) and K(sv)
      (quenching constant) had been obtained in the order: 1>2, consisted with the
      antitumor activity results. Taken together, complex 1 exhibited excellent
      antitumor activity suggesting that it may be a potential candidate for further
      chemical optimization and cancer therapy.

PMID- 25960225
TI  - miR-20a mediates temozolomide-resistance in glioblastoma cells via negatively
      regulating LRIG1 expression.
AB  - AIMS: Resistance to temozolomide (TMZ) is a major obstacle in the treatment of
      glioblastoma multiforme (GBM). MiRNAs is considered as an important modulator of
      drug resistance in many cancers. Here, we aimed to elucidate the relationship
      between miR-20a, its predicted target genes leucine-rich repeats and
      immunoglobulin-like domains 1 (LRIG1) and TMZ resistance in GBM. MAIN METHODS:
      Real-time PCR or western blot was used to measure the levels of miR-20a and
      LRIG1. The cell viability was obtained to investigate the sensitivity of U251
      cells and TMZ-resistant U251 (U251/TMZ) cells to TMZ. MiR-20a inhibitor or miR
      20a mimic was used to down-regulate or up-regulate miR-20a expression. The
      interaction between miR-20a and its predicted target gene LRIG1 was confirmed by
      3'-UTR dual-luciferase reporter assay. RNAi was used to knockdown LRIG1
      expression. A xenograft tumor model was used to investigate the in vivo antitumor
      activity. KEY FINDINGS: MiR-20a was highly expressed and LRIG1 lowly expressed in
      U251/TMZ cells. Knockdown of miR-20a by treatment with miR-20a inhibitor restored
      sensitivity of U251/TM cells to TMZ in vivo and in vitro, whereas overexpression
      of miR-20a by treatment with miR-20a mimic resulted in increased TMZ resistance.
      The levels of LRIG1 were inversely related to miR-20a levels. And the luciferase
      reporter assays showed that miR-20a directly targeted the 3'UTR of LRIG1. In
      addition, functional knock-down of LRIG1 by gene specific siRNA reversed the
      effect of miR-20a inhibitor. SIGNIFICANCE: MiR-20a mediated TMZ-resistance in
      glioblastoma cells through negatively regulating LRIG1 expression, which
      suggesting that miR-20a and LRIG1 would be potential therapeutic targets for
      glioma therapy.

PMID- 25960228
TI  - CD26 a cancer stem cell marker and therapeutic target.
AB  - Cancer stem cells (CSCs) comprise a tumor subpopulation responsible for tumor
      maintenance, resistance to chemotherapy, recurrence and metastasis. The
      identification of this cell group is very important, but there is still no
      consensus on its characterization. Several CSC markers have been described, like
      CD133, CD24, CD44 and ALDH1, but more research to identify new markers to
      facilitate the identification of CSC in a heterogeneous tumoral mass is required.
      Thus, this article describes the CD26 expression as a CSC marker and the role
      that it plays in different types of cancer. CD26 expression correlates with some
      characteristics of CSCs, like the formation of spheres in vitro, formation of new
      tumors, and resistance to chemotherapy. CD26 is therefore suggested as an
      auxiliary marker for CSC in different types of cancer, and as a potential
      therapeutic target. 

PMID- 25960229
TI  - Sevoflurane attenuate hypoxia-induced VEGF level in tongue squamous cell
      carcinoma cell by upregulating the DNA methylation states of the promoter region.
AB  - Anaesthetic agents were confirmed to play a role on the tumor angiogenesis. The
      effect of sevoflurane on tongue squamous cell carcinoma (TSCC) cell has not been
      investigated. SCC-4 cells were exposed to sevoflurane after simulating hypoxia.
      Then, both the mRNA and protein level of hypoxia-inducible factor (HIF)-1alpha
      and VEGF were detected. The methylation states of the VEGF promoter region were
      also assessed to reveal the underlying mechanism. Finally, the DNA
      methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-Aza) was administrated to
      reveal the relationship of DNA methylation on the regulation of the VEGF level.
      Results showed that sevoflurane attenuated the hypoxia-induced VEGF level without
      altering the HIF-1alpha after exposure for 24 and 72 h. Sevoflurane increased the
      DNA methylation of the VEGF promoter region. The attenuation effect of
      sevoflurane on hypoxia-induced VEGF level could be blocked by 5-Aza. We concluded
      that sevoflurane attenuates hypoxia-induced VEGF level via DNA methylation of the
      promoter region in TSCC cell.

PMID- 25960230
TI  - Use of ligand-based pharmacophore modeling and docking approach to find novel
      acetylcholinesterase inhibitors for treating Alzheimer's.
AB  - Alzheimer's disease is a neurological disorder in which the patient suffers from
      memory loss and impaired cognitive abilities. Though the main cause of the
      disease is not yet known, depletion of neurotransmitter at synaptic junctions,
      accumulation of insoluble beta amyloid plaques and neurofibrillary tangles are
      the main pathologies associated with it. The FDA approved drugs for alzheimer's
      belong to the category of acetylcholinesterase inhibitors. But most of the drugs
      have been observed to be associated with adverse side effects. In this study, we
      have developed a pharmacophore (responsible for interaction with
      acetylcholinesterase active site) based on the already existing drugs and drug
      candidates. This pharmacophore was used to search for novel AChE inhibitors with
      altogether different chemical scaffold using high throughput virtual screening
      and docking studies. Finally, we have reported two compounds, OPA and OMT, which
      possess high affinity for catalytic site of AChE enzyme and thus, can be
      considered as potential AChE inhibitors for the symptomatic treatment of
      Alzheimer's. 

PMID- 25960231
TI  - Effects of cell-penetrating peptides on transduction efficiency of PEGylated
      adenovirus.
AB  - BACKGROUND: Adenovirus (Ad) is one of the viral vectors most widely used for gene
      delivery. The virus, however, has serious shortcomings such as immunogenicity,
      promiscuous tropism, and the inability to efficiently infect certain types of
      cells. The goal of this study was to improve the ability of an Ad-based vector to
      efficiently transform cells that lack the native coxsackie-adenovirus receptor
      (CAR(-)) by modifying the virus with CPP-PEG conjugates. METHODS: The vector was
      produced by PEGylating Ad, which packages a lacZ reporter gene, and then
      conjugating CPPs to form CPP-PEG-Ad particles. The study compared the
      effectiveness of four different CPPs: Pen, Tat, Pep1, and pArg. The effects of
      CPP amount per virus, degree of PEGylation, and PEG molecular weight on
      transduction efficiency were studied on CAR(-) NIH/3T3 cells. RESULTS: CPP-PEG-Ad
      particles transduced CAR(-) cells significantly better than unmodified Ad. Pen,
      the most effective CPP, produced an 80-fold improvement in transduction compared
      to the unmodified virus. The Pen peptide utilized a combination of electrostatic
      and hydrophobic interactions with the cell membrane to maximize cellular
      association while the other CPPs used only electrostatic or hydrophobic
      interactions but not both. Lastly, higher degrees of PEGylation, which prompted
      PEG to adopt a "brush" conformation, resulted in more efficient CPP-PEG-Ad
      particles because of both better conjugation of CPPs to the PEGylated virus and
      better exposure of the conjugated CPPs on the surface of the particle.
      CONCLUSIONS: CPP-PEG-Ad particles efficiently deliver genes to cells that Ad
      alone would not efficiently infect, thereby extending potential gene therapy
      treatments to a much broader range of cell types and diseases.

PMID- 25960232
TI  - Inhibition of PI3K signaling triggered apoptotic potential of curcumin which is
      hindered by Bcl-2 through activation of autophagy in MCF-7 cells.
AB  - Curcumin is a natural anti-cancer agent derived from turmeric (Curcuma longa).
      Curcumin triggers intrinsic apoptotic cell death by activating mitochondrial
      permeabilization due to the altered expression of pro- and anti-apoptotic Bcl-2
      family members. Phosphoinositol-3-kinase (PI3K) and Akt, key molecular players in
      the survival mechanism, have been shown to be associated with the Bcl-2 signaling
      cascade; therefore, evaluating the therapeutic efficiency of drugs that target
      both survival and the apoptosis mechanism has gained importance in cancer
      therapy. We found that Bcl-2 overexpression is a limiting factor for curcumin
      induced apoptosis in highly metastatic MCF-7 breast cancer cells. Forced
      overexpression of Bcl-2 also blocked curcumin-induced autophagy in MCF-7 cells,
      through its inhibitory interactions with Beclin-1. Pre-treatment of PI3K
      inhibitor LY294002 enhanced curcumin-induced cell death, apoptosis, and autophagy
      via modulating the expression of Bcl-2 family members and autophagosome formation
      in MCF-7 breast cancer cells. Atg7 silencing further increased apoptotic
      potential of curcumin in the presence or absence of LY294002 in wt and Bcl-2+ MCF
      7 cells. The findings of this study support the hypothesis that blocking the
      PI3K/Akt pathway may further increased curcumin-induced apoptosis and overcome
      forced Bcl-2 expression level mediated autophagic responses against curcumin
      treatment in MCF-7 cells. 

PMID- 25960233
TI  - Increased sensitivity of human lung adenocarcinoma cells to cisplatin associated
      with downregulated contactin-1.
AB  - Contactin-1 (CNTN-1), a glycosyl phosphatidylinositol anchor neural cell adhesion
      molecule (ACAM), is thought to function not only in nervous system development
      but also in the invasion and metastasis of several tumours. To investigate
      whether CNTN-1 is involved in multidrug resistance (MDR) in lung adenocarcinoma,
      CNTN-1 expression was compared between MDR human lung adenocarcinoma
      A549/cisplatin (A549/DDP) cells and its progenitor A549 cells. The comparison
      showed that CNTN-1 expression in A549/DDP cells was significantly higher than in
      A549 cells both at the mRNA level and the protein level. In order to confirm the
      physiological function of the abnormal expression, lentivirus-mediated short
      hairpin RNA (shRNA) was used to silence CNTN-1. Cell cytotoxicity assay and cell
      apoptosis assay revealed that silencing CNTN-1 both in A549 cells and in A549/DDP
      cells not only rendered cells more sensitive to cisplatin than the negative
      control, but also increased the cisplatin-induced apoptosis. Metastasis and
      invasion assays demonstrated that CNTN-1 knockdown reduced metastasis and
      invasion but did not affect A549 or A549/DDP cell proliferation. To investigate
      whether the abnormal expression of CNTN-1 is associated with characteristics of
      patients with non-small cell lung cancer (NSCLC), immunohistochemistry was used
      to detect CNTN-1 expression in 143 tissue samples from NSCLC patients and the
      results showed that the degree of CNTN-1 expression positively correlated with
      lymphatic invasion in patients with lung adenocarcinoma who received adjuvant
      cisplatin- or carboplatin-based treatment after surgery. Thus, we concluded that
      CNTN-1 is closely related with MDR of lung adenocarcinoma. Additionally, CNTN-1
      is a novel marker to predict chemotherapeutic efficacy of patients with lung
      adenocarcinoma, especially with regard to cisplatin- or carboplatin-based
      regimens. 

PMID- 25960234
TI  - MicroRNA-133a improves the cardiac function and fibrosis through inhibiting Akt
      in heart failure rats.
AB  - OBJECTIVE: MicroRNAs (miRNAs), a group of small non-coding RNAs that fine tune
      translation of multiple target mRNAs, have been implicated in the development and
      progression of heart failure. METHODS: The present study was undertaken to
      determine the roles of miR-133a on the anatomical, hemodynamic and fibrosis of
      heart in the chronic heart failure rats, and the downstream signaling pathway.
      RESULTS: The expression of miR-133a in the heart of chronic heart failure from
      patients or rats was decreased. The miR-133a mimic and miR-133a overexpression
      caused a decrease in the heart weight/body weight (HW/BW) and LVEDP, and an
      increase in the LVSP and +LV dP/dt(max) in the chronic heart failure rats.
      However, the miR-133a inhibitor promoted the HW/BW and LVEDP, and caused a
      decrease in the LVSP and LV dP/dt(max) in the chronic heart failure rats. The miR
      133a mimic and miR-133a overexpression significantly caused a decrease in the
      fibrosis of heart in chronic heart failure rats. The Akt inhibitor TCN abolished
      the effects of miR-133a on the HW/BW and LVEDP decrease, LVSP and LV dP/dt(max)
      increase in the chronic heart failure rats. The miR-133a increased the expression
      of phosphorylated Akt in the heart of chronic heart failure rats. CONCLUSION:
      These results demonstrated that miR-133a improves the cardiac function and
      fibrosis through inhibiting Akt in heart failure rats.

PMID- 25960235
TI  - Update on the role of autophagy in systemic lupus erythematosus: A novel
      therapeutic target.
AB  - Systemic lupus erythematosus (SLE), induced by the interaction of susceptibility
      genes and environment risk factors, is a classical autoimmune diseases
      characterized by the dysregulation of innate and adaptive immune systems.
      Recently, evidence from genetic, cell biology and animal models suggested
      autophagy, a major pathway for organelle and protein turnover, plays a pivotal
      role in the occurrence and development of SLE, but not yet fully elucidated. We
      summarized an update on the recognized key principles of autophagy in SLE and
      focused our attention on the role of autophagy, including two main signaling
      pathways including mTOR and Beclin-1, in immune cells, such as B cell, T cell,
      neutrophils, etc. in SLE. Also, effects of currently used biological and chemical
      therapeutic drugs on autophagy in SLE were discussed. Autophagy may provide new
      targets for both diagnostic and therapeutic approaches for SLE although some
      results are still controversial, which worth more in-depth discussion in the
      future. 

PMID- 25960236
TI  - Silencing of TRPC1 regulates store-operated calcium entry and proliferation in
      Huh7 hepatocellular carcinoma cells.
AB  - PURPOSE: Previously, we observed reciprocal changes in TRPC1 and TRPC6 expression
      levels in aging rat aorta and A7r5, rat embryonic vascular smooth muscle cells.
      Furthermore, downregulation of TRPC1 significantly elevated store-operated Ca(2+)
      entry suggesting the regulatory role of TRPC1 in A7r5 cells. Since TRPC6
      upregulation shown to be associated with cell proliferation, the purpose of our
      study was to investigate the functional consequences of TRPC1 ion channel
      downregulation by RNA interference in Huh7 human hepatocellular carcinoma cell
      line. METHODS: Huh7 cells used in quantitative gene and protein expression as
      well as in functional analyses. To determine mRNA and protein levels,
      quantitative real-time RT-PCR and western blot analyses were performed,
      respectively. In functional analyses, real-time changes in proliferation,
      migration and intracellular Ca(2+) levels were monitored. RESULTS: In shTRPC1
      transfected Huh7 cells, TRPC1 mRNA and protein levels significantly decreased
      whereas store-operated Ca(2+) entry significantly elevated. TRPC1-silencing
      suppressed cell proliferation without affecting cell migration in real-time
      cellular analyses. CONCLUSION: These results suggest that TRPC1 may take part
      both in regulation of store-operated Ca(2+) entry and proliferation of
      hepatocellular carcinoma cells.

PMID- 25960237
TI  - Effect of Baliospermum montanum nanomedicine apoptosis induction and anti
      migration of prostate cancer cells.
AB  - Prostate cancer has been diagnosed as the second most frequent and the sixth
      among the cancer causing deaths among men worldwide. There is a limited scope for
      the prevalent therapies as prostate cancer advances and they present adverse
      aftermaths that have put way for us to delve into naturally available anticancer
      agents. The main objective of the present work is to compile the advantages of
      ayurvedic herbal formulations with modern technology. Baliospermum montanum is a
      plant that is used in ayurveda for the treatment of cancer and the plant is
      studied to possess various constituents in it that are responsible for its
      anticancer activity. Stable nanoparticles of B. montanum were prepared from both
      the aqueous and ethanolic extracts of the plant and its cytotoxic effects were
      studied on prostate cancer and normal cell lines. Size analysis by DLS and SEM
      revealed the average size of nanoparticles prepared was 100+/-50 nm and 150+/-50
      nm for the nanoparticles prepared from aqueous and ethanolic extract
      respectively. In vitro cytotoxicity showed a concentration and time dependent
      toxicity on prostate cancer cells with cell viability of 22% and 6% with maximum
      concentration of aqueous and ethanolic nanoparticles respectively, in 48 h. In
      vitro hemolysis assay confirmed that the prepared nanoparticles were compatible
      with blood with no occurrence of hemolysis. The nanoparticles showed a
      significant reduction in the colony forming ability and wound healing capacity of
      the prostate cancer cells. These studies hold the anti cancer potential of the B.
      montanum nanoparticles making it an important candidate for prostate cancer
      therapy.

PMID- 25960238
TI  - Prognostic significance of combined microRNA-206 and CyclinD2 in gastric cancer
      patients after curative surgery: A retrospective cohort study.
AB  - AIM: To investigate associations of microRNA (miR)-206 and CyclinD2 (CCND2)
      expression, alone or in combination, with clinicopathological characteristics and
      patients' prognosis in gastric cancer. METHODS: MiR-206 and CCND2 mRNA expression
      levels were detected by real-time quantitative RT-PCR in 220 self-pairs of
      gastric cancer and adjacent non-cancerous tissues. RESULTS: Compared with the
      adjacent non-cancerous tissues, the expression levels of miR-206 and CCND2 mRNA
      were respectively reduced and elevated in gastric cancer tissues dramatically
      (both P<0.001). Notably, the expression levels of miR-206 in gastric cancer
      tissues were negatively correlated with those of CCND2 mRNA significantly (r=
      0.463, P<0.001). Then, statistical analysis showed that low miR-206 expression
      and high CCND2 expression, alone or in combination, were all significantly
      associated with great depth of invasion, positive lymph node and distant
      metastases, and advanced TNM stage of human gastric cancer (all P<0.05). After
      that, we also found that the overall survivals of the patients with low miR-206
      expression and high CCND2 expression were respectively shorter than those with
      high miR-206 expression and low CCND2 expression. More interestingly, miR-206
      low/CCND2-high expression was associated with a significantly worst overall
      survival of all miR-206/CCND2 groups (P<0.001). Furthermore, multivariate
      analysis identified miR-206 and/or CCND2 expression as independent prognostic
      factors for overall survival in patients with gastric cancer. CONCLUSION: Our
      data provide evidence that the dysregulation of miR-206-CCND2 axis may contribute
      to the aggressive progression and poor prognosis of human gastric cancer in
      clinical settings. Combined detection of their expression might be particularly
      helpful for surveillance of disease progression and treatment stratification.

PMID- 25960239
TI  - Application of the Apc(Min/+) mouse model for studying inflammation-associated
      intestinal tumor.
AB  - Chronic inflammatory diseases of the intestinal tract have been known to increase
      risk of developing a form of colorectal cancer known as inflammation-associated
      cancer. The roles of inflammation in tumor formation and development in
      Apc(Min/+) mice have been broadly corroborated. The Apc(Min/+) mouse model
      contains a point mutation in the adenomatous polyposis coli (Apc) gene and only
      develops intestinal precancerous lesions, the benign adenomas. Thus, it provides
      an excellent in vivo system to investigate the molecular events involved in the
      inflammatory process which may contribute to multistep tumorigenesis and
      carcinogenesis. Recent investigations that employ this model studied the effects
      of gene alterations, intestinal microorganisms, drugs, diet, exercise and sleep
      on the inflammatory process and tumor development, and revealed the mechanisms
      involved in the formation, promotion and carcinogenesis of adenomas with the
      background of inflammation. Herein, we focus our review on the application of the
      Apc(Min/+) mouse model for studying inflammation-associated intestinal tumor and
      find that anti-inflammation is a possible strategy in combating intestinal tumor,
      but sometimes anti-inflammation cannot help reduce tumor burden. Moreover,
      various inflammation-related genes are involved in different mechanistic stages
      of tumor in Apc(Min/+) mice and intricate regulatory effects of inflammation
      exist in the whole progression of intestinal tumor. 

PMID- 25960240
TI  - Diagnostic and prognostic potentials of microRNA-27a in osteosarcoma.
AB  - AIM: Growing evidence suggest that the microRNA (miR)-23a/24-2/27a cluster may
      play a crucial role in mammary tumorigenesis and act as a novel class of
      oncogenes. Among these members, miR-27a has been reported to promote
      proliferation, migration and invasion in human osteosarcoma cells. The aim of
      this study was to detect the serum levels of miR-27a in osteosarcoma patients and
      to investigate its associations with clinicopathological features and prognosis.
      METHODS: miR-27a levels in sera from 166 osteosarcoma patients and 60 healthy
      controls were detected by real-time quantitative RT-PCR. Then, the associations
      of serum miR-27a level with clinicopathological factors or survival of
      osteosarcoma patients were further evaluated. RESULTS: Compared to healthy
      controls, the serum levels of miR-27a were significantly increased in
      osteosarcoma patients (P<0.001). Importantly, miR-27a could efficiently screen
      osteosarcoma patients from healthy controls (Area under receiver operating
      characteristic curve, AUC=0.867). Then, high miR-27a expression was more
      frequently occurred in osteosarcoma patients with advanced clinical stage
      (P=0.001), positive distant metastasis (P=0.01) and poor response to chemotherapy
      (P=0.008). In Kaplan-Meier survival analysis, high miR-27a expression was a
      significant indicator for poor overall survival (P=0.006) as well as poor disease
      free survival (P=0.01). Furthermore, multivariate analysis demonstrated that miR
      27a expression was an independent and significant prognostic factor to predict
      overall survival (P=0.01) and disease-free survival (P=0.03). CONCLUSION: miR-27a
      expression may be elevated in sera of osteosarcoma patients and in turn
      contributes to aggressive progression of this malignancy. Detection of serum miR
      27a levels may have clinical potentials as a non-invasive diagnostic/prognostic
      biomarker for osteosarcoma patients.

PMID- 25960241
TI  - The effects of HAART on the expression of MUC1 and P65 in a cervical cancer cell
      line, HCS-2.
AB  - Cervical cancer is the third most commonly diagnosed cancer globally and it is
      one of three AIDS defining malignancies. Highly active antiretroviral therapy
      (HAART) is a combination of three or more antiretroviral drugs and has been shown
      to play a significant role in reducing the incidence of some AIDS defining
      malignancies, although its effect on cervical cancer is still unclear. The aim of
      this study was to investigate the relationship between cervical cancer and HAART.
      This was achieved by studying the expression of two signalling molecules
      expressed in cervical cancer; MUC1 and P65. Following the 24-hour treatment of a
      cervical cancer cell line, HCS-2, with drugs, which are commonly used as part of
      HAART at their clinical plasma concentrations, real-time qPCR and
      immunofluorescence were used in order to study gene and protein expression. A one
      way ANOVA followed by a Tukey-Kramer post-hoc test was conducted using JMP 11
      software on both sets of data. The drug classified as a protease inhibitor (PI)
      (i.e. LPV/r) reduced MUC1 and P65 gene and protein expression more than the other
      drug tested. PIs are known to play a significant role in cell death; therefore,
      the cells were thought to be more susceptible to cell death following treatment
      with PIs. In conclusion, the drugs used, especially the PI showed some anticancer
      effects by facilitating cell death through decreased gene and protein expression
      of MUC1 and P65 and present promising agents for cancer treatment. 

PMID- 25960242
TI  - Circadian-time dependent tolerance and haematological toxicity to isoniazid in
      murine.
AB  - INTRODUCTION: Isoniazid (INH) is a widely used drug in the prophylaxis and
      treatment of tuberculosis. In the present study, isoniazid (INH)-induced toxicity
      was investigated according to the dosing-time in the 24-h scale in mice. METHODS:
      Two studies were carried out on a total of 180 male Swiss mice synchronized for 3
      weeks to 12-hour light (rest) and 12-hour dark (activity) cycle (L/D: 12/12). In
      the first study a potentially lethal dose of INH (180 mg/kg) was administered by
      intraperitoneal (i.p.) route at six different circadian-times: 1, 5, 9, 13, 17
      and 21 hours after light onset (HALO). In the second one, a sublethal dose (120
      mg/kg) was administered at three circadian-times (1, 9 and 17 HALO) in order to
      evaluate the variation of haematological toxicity. Rectal temperature, body
      weight loss, survival (study 1) and complete cell count (study 2) were determined
      as toxicity endpoints. The Cosinor and ANOVA methods were used for the data
      statistical analysis. RESULTS: The Cosinor analysis of rectal temperature time
      series prior to treatment validated a circadian rhythm, which demonstrates that
      mice were well synchronized. Following INH injection, rectal temperature
      increased in all the six circadian stages at days 2 and 3. Body weight loss
      varied from -12% at 1 HALO to -7% at 13 HALO (P<0.001). The 24-h mean of
      mortality induced by INH was 38%. Such lethal toxicity varied according to the
      circadian dosing-time. Maximum (60%) and minimum (20%) survival rates were
      observed when INH was administered at 9 and 1 HALO respectively. The highest
      survival time (25 days) occurred when INH was injected at 9 HALO while the lowest
      survival time (7 days) occurred when INH was given at 1 HALO. The decrease of
      haematological variables (cytopenia) was dependent on the circadian dosing-time
      (P<0.001). The least haematological toxicity illustrated by leukopenia index,
      anaemia and thrombocytopenia was observed in the middle of the second half of the
      light-rest phase (9 HALO).

PMID- 25960244
TI  - Clinical characteristics and long-term outcome of Taiwanese children with
      congenital hyperinsulinism.
AB  - BACKGROUND/PURPOSE: Congenital hyperinsulinism (CHI) is a rare condition causing
      severe hypoglycemia in neonates and infants due to dysregulation of insulin
      secretion. This study aimed to review 20 years' experience in the management of
      Taiwanese children with CHI. METHODS: Between 1990 and 2010, children diagnosed
      with CHI and followed up at the Pediatric Endocrine Clinic of the National Taiwan
      University Hospital were enrolled. Their medical records were thoroughly
      reviewed. RESULTS: In total, 13 patients (8 boys and 5 girls) were enrolled,
      including six patients with onset of hypoglycemia within 1 month of age and seven
      patients at 4.0 +/- 2.1 months of age. The birth weight standard deviation scores
      of these two age groups were 4.6 +/- 1.8 and 1.4 +/- 1.3 standard deviation
      score, respectively (p < 0.01). Initial intravenous glucose infusion at rates of
      22.9 +/- 5.3 mg/kg/min and 13.4 +/- 5.6 mg/kg/min, respectively, were mandatory
      to maintain euglycemia in these two groups (p < 0.05). All received
      pancreatectomy after failure of initial medical treatment. Twelve patients were
      followed up for a period of 2.5-19.8 years. Eight of them remained euglycemic
      without any medication and three patients developed diabetes mellitus. Seven of
      the nine patients who underwent intelligence evaluation had normal mental
      outcomes. Mental retardation of two patients was too severe to be evaluated. All
      four patients with mental retardation had a delay in the maintenance of
      euglycemia, and three of them also had seizure disorder. CONCLUSION: The age at
      onset of hypoglycemia reflects the severity of CHI. Early diagnosis and
      appropriate treatment are important for favorable mental outcomes.

PMID- 25960243
TI  - ZnPPIX inhibits peritoneal metastasis of gastric cancer via its antiangiogenic
      activity.
AB  - Our previous study suggests that heme oxygenase-1 (HO-1) may play an important
      role in the metastasis of gastric cancer. Zinc protoporphyrin IX (ZnPPIX) is a
      special HO-1 inhibitor that inhibits the angiogenesis of pancreatic and lung
      cancer. In this study, we employed ZnPPIX to investigate the role of HO-1 in
      peritoneal metastasis of gastric cancer (PMGC) and explored the potential
      mechanism. We established animal model of PMGC by orthotopic implantation into
      nude mice of human gastric cancer cell line GC9811-P with high peritoneal
      metastasis potential. The mice were injected intraperitoneally with saline, CTX
      or ZnPPIX. Tumor microvessel density (MVD) in peritoneal metastatic nodules was
      determined by immunohistochemistry, and vascular endothelial growth factor (VEGF)
      level was determined by ELISA. We found that the number, volume, weight of
      peritoneal metastatic nodules and volume of seroperitoneum in ZnPPIX (4 mg/kg)
      group decreased remarkably compared with control group. MVD value and VEGF level
      of peritoneal metastatic tumor in ZnPPIX (4 mg/kg) group also decreased
      significantly, while the survival rate and survival time of the mice were higher
      than control group. ZnPPIX dose-dependently suppressed VEGF and GC9811-P induced
      angiogenesis. Furthermore, ZnPPIX suppressed VEGF induced reactive oxygen species
      production and ERK phosphorylation in human umbilical vein endothelial cells. In
      conclusion, our results suggest that HO-1 plays an important role in PMGC and
      ZnPPIX is an effective antitumor and antiangiogenic agent for PMGC.

PMID- 25960245
TI  - Condyloma acuminatum manifests as intranasal papillomatosis.

PMID- 25960246
TI  - Recovery and removal of nutrients from swine wastewater by using a novel
      integrated reactor for struvite decomposition and recycling.
AB  - In the present study, struvite decomposition was performed by air stripping for
      ammonia release and a novel integrated reactor was designed for the simultaneous
      removal and recovery of total ammonia-nitrogen (TAN) and total orthophosphate
      (PT) from swine wastewater by internal struvite recycling. Decomposition of
      struvite by air stripping was found to be feasible. Without supplementation with
      additional magnesium and phosphate sources, the removal ratio of TAN from
      synthetic wastewater was maintained at >80% by recycling of the struvite
      decomposition product formed under optimal conditions, six times. Continuous
      operation of the integrated reactor indicated that approximately 91% TAN and 97%
      PT in the swine wastewater could be removed and recovered by the proposed
      recycling process with the supplementation of bittern. Economic evaluation of the
      proposed system showed that struvite precipitation cost can be saved by
      approximately 54% by adopting the proposed recycling process in comparison with
      no recycling method. 

PMID- 25960247
TI  - The Close Relationships of People with Intellectual Disabilities: A Qualitative
      Study.
AB  - BACKGROUND: Positive interpersonal relationships have been found to enhance an
      individual's quality of life. However, people with intellectual disabilities
      (PWID) often have restricted social networks, and little is known about their
      views on close social relationships. The study aimed to explore how this group
      perceives and experiences close relationships. MATERIALS AND METHODS: Ten (6 =
      men 4 = women) PWID participated. Data were collected using semi-structured
      interviews, and analysed using interpretive phenomenological analysis. RESULTS:
      The results report on three of five themes drawn from a larger qualitative study:
      'Relationships feeling safe and being useful'; 'Who's in charge?' and 'Struggling
      for an ordinary life'. CONCLUSIONS: Close relationships are valued and desired by
      PWID, but a variety of barriers inhibit their development and maintenance. This
      includes the failure of others to value, accept and appropriately support the
      independence and relationships of PWID. Potential ways of addressing these issues
      are discussed.

PMID- 25960248
TI  - Expression of fungal acetyl xylan esterase in Arabidopsis thaliana improves
      saccharification of stem lignocellulose.
AB  - Cell wall hemicelluloses and pectins are O-acetylated at specific positions, but
      the significance of these substitutions is poorly understood. Using a transgenic
      approach, we investigated how reducing the extent of O-acetylation in xylan
      affects cell wall chemistry, plant performance and the recalcitrance of
      lignocellulose to saccharification. The Aspergillus niger acetyl xylan esterase
      AnAXE1 was expressed in Arabidopsis under the control of either the
      constitutively expressed 35S CAMV promoter or a woody-tissue-specific GT43B aspen
      promoter, and the protein was targeted to the apoplast by its native signal
      peptide, resulting in elevated acetyl esterase activity in soluble and wall-bound
      protein extracts and reduced xylan acetylation. No significant alterations in
      cell wall composition were observed in the transgenic lines, but their xylans
      were more easily digested by a beta-1,4-endoxylanase, and more readily extracted
      by hot water, acids or alkali. Enzymatic saccharification of lignocellulose after
      hot water and alkali pretreatments produced up to 20% more reducing sugars in
      several lines. Fermentation by Trametes versicolor of tissue hydrolysates from
      the line with a 30% reduction in acetyl content yielded ~70% more ethanol
      compared with wild type. Plants expressing 35S:AnAXE1 and pGT43B:AnAXE1 developed
      normally and showed increased resistance to the biotrophic pathogen
      Hyaloperonospora arabidopsidis, probably due to constitutive activation of
      defence pathways. However, unintended changes in xyloglucan and pectin
      acetylation were only observed in 35S:AnAXE1-expressing plants. This study
      demonstrates that postsynthetic xylan deacetylation in woody tissues is a
      promising strategy for optimizing lignocellulosic biomass for biofuel production.

PMID- 25960249
TI  - Intermittent stretching induces fibrosis in denervated rat muscle.
AB  - INTRODUCTION: Stretching (St) has been used for treating denervated muscles.
      However, its effectiveness and safety claims require further study. METHODS: Rats
      were divided into: (1) those with denervated (D) muscles, evaluated 7 or 15 days
      after sciatic nerve crush injury; (2) those with D muscles submitted to St during
      7 or 15 days; and (3) those with normal muscles. Muscle fiber cross-sectional
      area, serial sarcomere number, sarcomere length, and connective tissue density
      were measured. MMP-2, MMP-9, TIMP-1, TGF-beta1, and myostatin mRNAs were
      determined by real-time polymerase chain reaction. MMP-2 and MMP-9 activity was
      evaluated by zymography. Collagen I was localized using immunofluorescence.
      RESULTS: St did not prevent muscle atrophy due to denervation, but it increased
      fibrosis and collagen I deposition at day 15. St also upregulated MMP-9 and TGF
      beta1 gene expressions at day 7, and myostatin at day 15. CONCLUSIONS: Stretching
      denervated muscle does not prevent atrophy, but it increases fibrosis via
      temporal modulation of TGF-beta1/myostatin and MMP-9 cascades.

PMID- 25960250
TI  - Matrix-assisted laser desorption/ionization-time of flight mass spectrometry
      identification of large colony beta-hemolytic streptococci containing Lancefield
      groups A, C, and G.
AB  - BACKGROUND: The aim of this study was to investigate whether large colony beta
      hemolytic streptococci containing Lancefield groups A, C, and G can be adequately
      identified using matrix-assisted laser desorption/ionization-time of flight mass
      spectrometry (MALDI-ToF). Previous studies show varying results, with an
      identification rate from below 50% to 100%. METHODS: Large colony beta-hemolytic
      streptococci containing Lancefield groups A, C, and G isolated from blood
      cultures between January 1, 2007 and May 1, 2012 were included in the study.
      Isolates were identified to the species level using a combination of phenotypic
      characteristics and 16s rRNA sequencing. The isolates were subjected to MALDI-ToF
      analysis. We used a two-stage approach starting with the direct method. If no
      valid result was obtained we proceeded to an extraction protocol. Scores above 2
      were considered valid identification at the species level. RESULTS: A total of 97
      Streptococcus pyogenes, 133 Streptococcus dysgalactiae, and 2 Streptococcus canis
      isolates were tested; 94%, 66%, and 100% of S. pyogenes, S. dysgalactiae, and S.
      canis, respectively, were correctly identified by MALDI-ToF. DISCUSSION: In most
      instances when the isolates were not identified by MALDI-ToF this was because
      MALDI-ToF was unable to differentiate between S. pyogenes and S. dysgalactiae. By
      removing two S. pyogenes reference spectra from the MALDI-ToF database the
      proportion of correctly identified isolates increased to 96% overall. MALDI-ToF
      is a promising method for discriminating between S. dysgalactiae, S. canis, and
      S. equi, although more strains need to be tested to clarify this.

PMID- 25960251
TI  - Longitudinal body composition of children born to mothers with normal weight,
      overweight, and obesity.
AB  - OBJECTIVE: The longitudinal trajectories of body composition of children born to
      mothers with normal weight, overweight, and obesity have not been evaluated using
      precise body composition methods. This study investigated the relationship
      between maternal prepregnancy BMI and offspring body composition trajectories
      during the first 6 years of life. METHODS: Healthy infants (N = 325) were
      assessed longitudinally (at ages 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, and 6 years)
      using dual-energy X-ray absorptiometry. Mixed-effects regression for repeated
      measures was used to model each continuous outcome as a function of maternal BMI
      and covariates (race, gestational age, birth weight, and mode of infant feeding).
      RESULTS: Maternal obesity differentially impacted body fat, but not bone mineral
      content or density, of girls and boys. Boys born to mothers with obesity have
      higher body fat from ages 2-6 years compared to boys born to normal-weight and
      overweight mothers (P < 0.05), whereas body composition of girls born to mothers
      with obesity was not different across groups during the first 6 years of life (P
      > 0.05). CONCLUSIONS: This clinical observational study demonstrates a sexual
      dimorphism in offspring body composition until age 6 years based on maternal BMI,
      with a greater effect of maternal adiposity seen in boys than in girls.

PMID- 25960252
TI  - Prediction of pH dependent absorption using in vitro, in silico, and in vivo rat
      models: Early liability assessment during lead optimization.
AB  - Weakly basic compounds which have pH dependent solubility are liable to exhibit
      pH dependent absorption. In some cases, a subtle change in gastric pH can
      significantly modulate the plasma concentration of the drug and can lead to sub
      therapeutic exposure of the drug. Evaluating the risk of pH dependent absorption
      and potential drug-drug interaction with pH modulators are important aspects of
      drug discovery and development. In order to assess the risk around the extent of
      decrease in the systemic exposure of drugs co-administered with pH modulators in
      the clinic, a pH effect study is carried out, typically in higher species, mostly
      dog. The major limitation of a higher species pH effect study is the resource and
      material requirement to assess this risk. Hence, these studies are mostly
      restricted to promising or advanced leads. In our current work, we have used in
      vitro aqueous solubility, in silico simulations using GastroPlusTM and an in vivo
      rat pH effect model to provide a qualitative assessment of the pH dependent
      absorption liability. Here, we evaluate ketoconazole and atazanavir with
      different pH dependent solubility profiles and based on in vitro, in silico and
      in vivo results, a different extent of gastric pH effect on absorption is
      predicted. The prediction is in alignment with higher species and human pH effect
      study results. This in vitro, in silico and in vivo (IVISIV) correlation is then
      extended to assess pH absorption mitigation strategy. The IVISIV predicts pH
      dependent absorption for BMS-582949 whereas its solubility enhancing prodrug, BMS
      751324 is predicted to mitigate this liability. Overall, the material requirement
      for this assessment is substantially low which makes this approach more practical
      to screen multiple compounds during lead optimization. 

PMID- 25960253
TI  - Inhibition of DNA topoisomerases I and II and growth inhibition of HL-60 cells by
      novel acridine-based compounds.
AB  - HL-60 cancer cells were treated with a series of novel acridine derivatives
      (derivatives 1-4) in order to test the compounds' ability to inhibit both cancer
      cell growth and topoisomerase I and II activity. Binding studies of derivatives 1
      4 with calf thymus DNA were also performed using a number of techniques (UV-Vis
      and fluorescence spectroscopy, thermal denaturation, linear dichroism and
      viscometry) to determine the nature of the interaction between the compounds and
      ctDNA. The binding constants for the complexes of the studied acridine
      derivatives with DNA were calculated from UV-Vis spectroscopic titrations
      (K=3.1*10(4)-2.0*10(3)M(-1)). Some of the compounds showed a strong inhibitory
      effect against Topo II at the relatively low concentration of 5MUM. Topo I/II
      inhibition mode assays were also performed and verified that the novel compounds
      are topoisomerase suppressors rather than poisons. The biological activities of
      derivatives were studied using MTT assay and flow cytometric methods (detection
      of mitochondrial membrane potential, measurement of cell viability) after 24 and
      48h incubation. The ability of derivatives to impair cell proliferation was
      tested by an analysis of cell cycle distribution. 

PMID- 25960255
TI  - Confirming Variants in Next-Generation Sequencing Panel Testing by Sanger
      Sequencing.
AB  - Current clinical laboratory practice guidelines for next-generation sequencing
      (NGS) do not provide definitive guidance on confirming NGS variants. Sanger
      confirmation of NGS results can be inefficient, redundant, and expensive. We
      evaluated the accuracy of NGS-detected single-nucleotide variants (SNVs) and
      insertion/deletion variants (indels) and the necessity of NGS variant
      confirmation using four NGS target-capture gene panels covering 117 genes, 568
      Kbp, and 77 patient DNA samples. Unique NGS-detected variants (1080 SNVs and 124
      indels) underwent Sanger confirmation and/or were compared to data from the 1000
      Genomes Project (1000G). Recurrent variants in unrelated samples resulted in 919
      comparisons between NGS and Sanger, with 100% concordance. In a second
      comparison, 762 unique NGS results (736 SNVs, 26 indels) from seven 1000G samples
      were found to have 97.1% concordance with 1000G phase 1 data. Sanger sequencing
      and 1000G phase 3 data confirmed the accuracy of the NGS results for all 1000G
      phase 1 discrepancies. In all samples, the depth of coverage exceeded 100* in
      >99.7% of bases in the target regions. In conclusion, confirmatory analysis by
      Sanger sequencing of SNVs detected via capture-based NGS testing that meets
      appropriate quality thresholds is unnecessarily redundant. In contrast, Sanger
      sequencing for indels may be required for defining the correct genomic location,
      and Sanger may be used for quality-assurance purposes. 

PMID- 25960254
TI  - Non-Cartesian balanced steady-state free precession pulse sequences for real-time
      cardiac MRI.
AB  - PURPOSE: To develop a new spiral-in/out balanced steady-state free precession
      (bSSFP) pulse sequence for real-time cardiac MRI and compare it with radial and
      spiral-out techniques. METHODS: Non-Cartesian sampling strategies are efficient
      and robust to motion and thus have important advantages for real-time bSSFP cine
      imaging. This study describes a new symmetric spiral-in/out sequence with
      intrinsic gradient moment compensation and SSFP refocusing at TE = TR/2. In vivo
      real-time cardiac imaging studies were performed to compare radial, spiral-out,
      and spiral-in/out bSSFP pulse sequences. Furthermore, phase-based fat/water
      separation taking advantage of the refocusing mechanism of the spiral-in/out
      bSSFP sequence was also studied. RESULTS: The image quality of the spiral-out and
      spiral-in/out bSSFP sequences was improved with off-resonance and k-space
      trajectory correction. The spiral-in/out bSSFP sequence had the highest signal-to
      noise ratio (SNR), contrast-to-noise ratio, and image quality ratings, with
      spiral-out bSSFP sequence second in each category and the radial bSSFP sequence
      third. The spiral-in/out bSSFP sequence provides separated fat and water images
      with no additional scan time. CONCLUSIONS: In this study, a new spiral-in/out
      bSSFP sequence was developed and tested. The superiority of spiral bSSFP
      sequences over the radial bSSFP sequence in terms of SNR and reduced artifacts
      was demonstrated in real-time MRI of cardiac function without image acceleration.

PMID- 25960256
TI  - Analytical Performance of a 15-Gene Prognostic Assay for Early-Stage Non-Small
      Cell Lung Carcinoma Using RNA-Stabilized Tissue.
AB  - A 15-gene prognostic signature for early-stage, completely resected, non-small
      cell lung carcinoma, (which distinguishes between patients with good and poor
      prognoses) was clinically validated in prior studies. To achieve operational
      efficiencies, this study was designed to evaluate the assay's performance in RNA
      stabilized tissue as an alternative to the fresh-frozen tissue format originally
      used to develop the assay. The percent concordance between matched tissue formats
      was 84% (95% Wilson CI, 70%-92%), a level of agreement comparable to the inherent
      reproducibility of the assay observed within biological replicates of fresh
      frozen tissue. Furthermore, the analytical performance of the assay using the RNA
      stabilized tissue format was evaluated. When compared to an accredited reference
      laboratory, the clinical laboratory achieved a concordance of 94% (95% Wilson CI,
      81%-98%), and there was no evidence of bias between the laboratories. The lower
      limit of quantitation for the target RNA concentration was confirmed to be, at
      most, 12.5 ng/MUL. The assay reportable range defined in terms of risk score
      units was determined to be -4.295 to 4.210. In a large-scale precision study, the
      assay showed high reproducibility and repeatability. When subjected to a maximal
      amount of genomic DNA, a potential contaminant, the assay still produced the
      expected results. The 15-gene signature was confirmed to produce reliable results
      and, thus, is suitable for its intended use. 

PMID- 25960257
TI  - FTIR spectroscopy for the detection and evaluation of live attenuated viruses in
      freeze dried vaccine formulations.
AB  - This article examines the applicability of Fourier Transform Infrared (FTIR)
      spectroscopy to detect the applied virus medium volume (i.e., during sample
      filling), to evaluate the virus state and to distinguish between different
      vaccine doses in a freeze dried live, attenuated vaccine formulation. Therefore,
      different formulations were freeze dried after preparing them with different
      virus medium volumes (i.e., 30, 100, and 400 ul) or after applying different pre
      freeze-drying sample treatments (resulting in different virus states); i.e., (i)
      as done for the commercial formulation; (ii) samples without virus medium
      (placebo); (iii) samples with virus medium but free from antigen; (iv)
      concentrated samples obtained via a centrifugal filter device; and (v) samples
      stressed by 96h exposure to room temperature; or by using different doses
      (placebo, 25-dose vials, 50-dose-vials and 125-dose vials). Each freeze-dried
      product was measured directly after freeze-drying with FTIR spectroscopy. The
      collected spectra were analyzed using principal component analysis (PCA) and
      evaluated at three spectral regions, which might provide information on the
      coated proteins of freeze dried live, attenuated viruses: (i) 1700-1600 cm(-1)
      (amide I band), 1600-1500 cm(-1) (amide II band) and 1200-1350 cm(-1) (amide III
      band). The latter spectral band does not overlap with water signals and is hence
      not influenced by residual moisture in the samples. It was proven that FTIR could
      distinguish between the freeze-dried samples prepared using different virus
      medium volumes, containing different doses and using different pre-freeze-drying
      sample treatments in the amide III region.

PMID- 25960258
TI  - Biosupercapacitors for powering oxygen sensing devices.
AB  - A biofuel cell comprising electrodes based on supercapacitive materials - carbon
      nanotubes and nanocellulose/polypyrrole composite was utilized to power an oxygen
      biosensor. Laccase Trametes versicolor, immobilized on naphthylated multi walled
      carbon nanotubes, and fructose dehydrogenase, adsorbed on a porous polypyrrole
      matrix, were used as the cathode and anode bioelectrocatalysts, respectively. The
      nanomaterials employed as the supports for the enzymes increased the surface area
      of the electrodes and provide direct contact with the active sites of the
      enzymes. The anode modified with the conducting polymer layer exhibited
      significant pseudocapacitive properties providing superior performance also in
      the high energy mode, e.g., when switching on/off the powered device. Three air
      fructose biofuel cells connected in a series converted chemical energy into
      electrical giving 2 mW power and open circuit potential of 2V. The biofuel cell
      system was tested under various externally applied resistances and used as a
      powering unit for a laboratory designed two-electrode minipotentiostat and a
      laccase based sensor for oxygen sensing. Best results in terms of long time
      measurement of oxygen levels were obtained in the pulse mode -45 s for
      measurement and 15 min for self-recharging of the powering unit.

PMID- 25960259
TI  - Hydrogen bioelectrooxidation on gold nanoparticle-based electrodes modified by
      Aquifex aeolicus hydrogenase: Application to hydrogen/oxygen enzymatic biofuel
      cells.
AB  - For the first time, gold nanoparticle-based electrodes have been used as
      platforms for efficient immobilization of the [NiFe] hydrogenase from the
      hyperthermophilic bacterium Aquifex aeolicus. AuNPs were characterized by
      electronic microscopy, dynamic light scattering and UV-Vis spectroscopy. Two
      sizes around 20.0+/-5.3 nm and 37.2+/-4.3 nm nm were synthesized. After thiol
      based functionalization, the AuNPs were proved to allow direct H2 oxidation over
      a large range of temperatures. A high current density up to 1.85+/-0.15 mA.cm(-2)
      was reached at the smallest AuNPs, which is 170 times higher than the one
      recorded at the bare gold electrode. The catalytic current was especially studied
      as a function of the AuNP size and amount, and procedure for deposition. A
      synergetic effect between the AuNP porous deposit and the increase surface area
      was shown. Compared to previously used nanomaterials such as carbon nanofibers,
      the covalent grafting of the enzyme on the thiol-modified gold nanoparticles was
      shown to enhance the stability of the hydrogenase. This bioanode was finally
      coupled to a biocathode where BOD from Myrothecium verrucaria was immobilized on
      AuNP-based film. The performance of the so-mounted H2/O2 biofuel cell was
      evaluated, and a power density of 0.25 mW.cm(-2) was recorded.

PMID- 25960260
TI  - Peptide macrocyclization by a bifunctional endoprotease.
AB  - Proteases usually cleave peptides, but under some conditions, they can ligate
      them. Seeds of the common sunflower contain the 14-residue, backbone-macrocyclic
      peptide sunflower trypsin inhibitor 1 (SFTI-1) whose maturation from its
      precursor has a genetic requirement for asparaginyl endopeptidase (AEP). To
      provide more direct evidence, we developed an in situ assay and used (18)O-water
      to demonstrate that SFTI-1 is excised and simultaneously macrocyclized from its
      linear precursor. The reaction is inefficient in situ, but a newfound breakdown
      pathway can mask this inefficiency by reducing the internal disulfide bridge of
      any acyclic-SFTI to thiols before degrading it. To confirm AEP can directly
      perform the excision/ligation, we produced several recombinant plant AEPs in E.
      coli, and one from jack bean could catalyze both a typical cleavage reaction and
      cleavage-dependent, intramolecular transpeptidation to create SFTI-1. We propose
      that the evolution of ligating endoproteases enables plants like sunflower and
      jack bean to stabilize bioactive peptides.

PMID- 25960261
TI  - PqsE of Pseudomonas aeruginosa Acts as Pathway-Specific Thioesterase in the
      Biosynthesis of Alkylquinolone Signaling Molecules.
AB  - Pseudomonas aeruginosa uses the alkylquinolones PQS (2-heptyl-3-hydroxy-4(1H)
      quinolone) and HHQ (2-heptyl-4(1H)-quinolone) as quorum-sensing signal molecules,
      controlling the expression of many virulence genes as a function of cell
      population density. The biosynthesis of HHQ is generally accepted to require the
      pqsABCD gene products. We now reconstitute the biosynthetic pathway in vitro, and
      demonstrate that in addition to PqsABCD, PqsE has a role in HHQ synthesis. PqsE
      acts as thioesterase, hydrolyzing the biosynthetic intermediate 2
      aminobenzoylacetyl-coenzyme A to form 2-aminobenzoylacetate, the precursor of HHQ
      and 2-aminoacetophenone. The role of PqsE can be taken over to some extent by the
      broad-specificity thioesterase TesB, explaining why the pqsE deletion mutant of
      P. aeruginosa still synthesizes HHQ. Interestingly, the pqsE mutant produces
      increased levels of 2,4-dihydroxyquinoline, resulting from intramolecular
      cyclization of 2-aminobenzoylacetyl-coenzyme A. Overall, our data suggest that
      PqsE promotes the efficiency of alkylquinolone signal molecule biosynthesis in P.
      aeruginosa and balances the levels of secondary metabolites deriving from the
      alkylquinolone biosynthetic pathway.

PMID- 25960263
TI  - A new design of organic radical batteries (ORBs): carbon nanotube buckypaper
      electrode functionalized by electrografting.
AB  - A novel hybrid material displaying a fast and reversible charge storage
      capability is prepared by electrografting of an alkoxyamine-bearing acrylate onto
      a carbon nanotube buckypaper, followed by the quantitative generation of an
      electroactive polynitroxide. 

PMID- 25960262
TI  - Targeting cholesterol in a liquid-disordered environment by theonellamides
      modulates cell membrane order and cell shape.
AB  - Roles of lipids in the cell membrane are poorly understood. This is partially due
      to the lack of methodologies, for example, tool chemicals that bind to specific
      membrane lipids and modulate membrane function. Theonellamides (TNMs), marine
      sponge-derived peptides, recognize 3beta-hydroxysterols in lipid membranes and
      induce major morphological changes in cultured mammalian cells through as yet
      unknown mechanisms. Here, we show that TNMs recognize cholesterol-containing
      liquid-disordered domains and induce phase separation in model lipid membranes.
      Modulation of membrane order was also observed in living cells following
      treatment with TNM-A, in which cells shrank considerably in a cholesterol-,
      cytoskeleton-, and energy-dependent manner. These findings present a previously
      unrecognized mode of action of membrane-targeting natural products. Meanwhile, we
      demonstrated the importance of membrane order, which is maintained by
      cholesterol, for proper cell morphogenesis.

PMID- 25960264
TI  - Autonomic involvement in Parkinsonian carriers of PARK2 gene mutations.
AB  - BACKGROUND AND OBJECTIVES: The objective of this study was to assess the presence
      of autonomic nervous system dysfunction in PARK2 mutation carriers. PATIENTS AND
      METHODS: We performed a cross-sectional analysis of 8 PARK2 carriers (age: 60.1
      +/- 12.8 years) and 13 individuals with idiopathic PD (iPD) (age: 59.2 +/- 8.9
      years). Autonomic dysfunction was measured using the SCOPA-AUT questionnaire, non
      invasive autonomic tests and responses of noradrenaline and vasopressin levels to
      postural changes. Myocardial sympathetic denervation was assessed with
      metaiodobenzylguanidine (MIBG) scintigraphy. This damage was further investigated
      in postmortem epicardial tissue of one PARK2 carrier and three control cases (two
      PD patients and one subject without PD). RESULTS: The prevalence of autonomic
      symptoms and orthostatic hypotension (OH) was lower in PARK2 mutation carriers
      than in iPD patients (SCOPA OUT: 3.4 +/- 4.8 vs. 14.7 +/- 7.2, p < 0.001; OH:
      present in three iPD patients but none of the PARK2 mutation carriers). Second,
      sympathetic myocardial denervation was less severe in PARK2 mutation carriers
      compared to controls, both in MIBG scintigraphy (late H/M uptake ratio: 1.52 +/-
      0.35 vs. 1.32 +/- 0.25 p < 0.05) and in postmortem tissue study. Interestingly,
      axonal alpha-synuclein deposits were absent in epicardial tissue of the PARK2
      mutation carrier while they were present in the two PD patients. INTERPRETATION:
      Our study supports the view that autonomic nervous system dysfunction and
      myocardial sympathetic denervation are less pronounced in PARK2 mutation carriers
      than in individuals with iPD, suggesting that the involvement of small peripheral
      sympathetic nerve fibers is a minor pathological hallmark in PARK2 carriers.

PMID- 25960266
TI  - Revising the International Health Regulations: call for a 2017 review conference.

PMID- 25960265
TI  - An Online Workplace Healthy Lunchbox Challenge for Adults.

PMID- 25960267
TI  - Improved and targeted delivery of bioactive molecules to cells with magnetic
      layer-by-layer assembled microcapsules.
AB  - Despite our increasing knowledge of cell biology and the recognition of an
      increasing repertoire of druggable intracellular therapeutic targets, there
      remain a limited number of approaches to deliver bioactive molecules to cells and
      even fewer that enable targeted delivery. Layer-by-layer (LbL) microcapsules are
      assembled using alternate layers of oppositely charged molecules and are
      potential cell delivery vehicles for applications in nanomedicine. There are a
      wide variety of charged molecules that can be included in the microcapsule
      structure including metal nanoparticles that introduce physical attributes.
      Delivery of bioactive molecules to cells with LbL microcapsules has recently been
      demonstrated, so in this study we explore the delivery of bioactive molecules
      (luciferase enzyme and plasmid DNA) to cells using biodegradable microcapsules
      containing a layer of magnetite nanoparticles. Interestingly, significantly
      improved intracellular luciferase enzyme activity (25 fold) and increased
      transfection efficiency with plasmid DNA (3.4 fold) was observed with magnetic
      microcapsules. The use of a neodymium magnet enabled efficient targeting of
      magnetic microcapsules which further improved the delivery efficiency of the
      cargoes as a consequence of increased microcapsule concentration at the magnetic
      site. Microcapsules were well tolerated by cells in these experiments and only
      displayed signs of toxicity at a capsule : cell ratio of 100 : 1 and with
      extended exposure. These studies illustrate how multi-functionalization of LbL
      microcapsules can improve and target delivery of bioactive molecules to cells. 

PMID- 25960269
TI  - Contact dermatitis caused by efinaconazole solution for treatment of
      onychomycosis.

PMID- 25960268
TI  - Functional Role of Histidine in the Conserved His-x-Asp Motif in the Catalytic
      Core of Protein Kinases.
AB  - The His-x-Asp (HxD) motif is one of the most conserved structural components of
      the catalytic core of protein kinases; however, the functional role of the
      conserved histidine is unclear. Here we report that replacement of the HxD
      histidine with Arginine or Phenylalanine in Aurora A abolishes both the catalytic
      activity and auto-phosphorylation, whereas the Histidine-to-tyrosine impairs the
      catalytic activity without affecting its auto-phosphorylation. Comparisons of the
      crystal structures of wild-type (WT) and mutant Aurora A demonstrate that the
      impairment of the kinase activity is accounted for by (1) disruption of the
      regulatory spine in the His-to-Arg mutant, and (2) change in the geometry of
      backbones of the Asp-Phe-Gly (DFG) motif and the DFG-1 residue in the His-to-Tyr
      mutant. In addition, bioinformatics analyses show that the HxD-histidine is a
      mutational hotspot in tumor tissues. Moreover, the H174R mutation of the HxD
      histidine, in the tumor suppressor LKB1 abrogates the inhibition of anchorage
      independent growth of A549 cells by WT LKB1. Based on these data, we propose that
      the HxD-histidine is involved in a conserved inflexible organization of the
      catalytic core that is required for the kinase activity. Mutation of the HxD
      histidine may also be involved in the pathogenesis of some diseases including
      cancer. 

PMID- 25960270
TI  - PAHs in the Ria de Arousa (NW Spain): A consideration of PAHs sources and
      abundance.
AB  - Analysis of 35 parental and alkylated homologues of PAHs (Polycyclic Aromatic
      Hydrocarbons) was carried out in eleven marine sediment samples collected along a
      central transect in the biggest Galician ria. The samples were collected using a
      box-core dredge and, after freeze-drying, were kept frozen until analysis. The
      sediments were extracted by PLE (Pressurized Liquid Extraction) procedure and the
      quantification of PAHs was performed using gas chromatography coupled to mass
      spectrometry (GC-MS) with the aid of deuterated PAH internal standards. The total
      concentration of studied PAHs (Sigma35PAHs) ranged from 44.8 to 7901ngg(-1) dry
      weight (d.w.). The highest PAH concentrations were found in sediments collected
      near the harbour (7901ngg(-1)) and the cleanest positions were located in the
      outer zone of the ria. To date, these results are the first data presented in the
      area so they could be used for regular monitoring and control of future pollution
      episodes. 

PMID- 25960271
TI  - Pb, Cu and Cd distribution in five estuary systems of Marche, central Italy.
AB  - Heavy metals are subjected to monitoring in estuarine and marine water by the
      European Union Water Framework Directive, which requires water body health to be
      achieved by 2021. This is the first survey of heavy metals content in five
      estuaries of Marche, a region in central Italy. Results showed that total Pb and
      Cu concentrations decreased by 70-80%, from 1000-2000 to 100-200 ng L(-1) (Pb)
      and from 2000-3000 to 500-1000 ng L(-1) (Cu) from river to sea. Cd was
      consistently 20-40 ng L(-1). Dissolved Pb and Cu concentrations declined by 50%
      and 70% respectively passing from oligohaline to euhaline water, from 150 to 70
      ng L(-1) and from 2000-1000 to 600-400 ng L(-1). Cd decreased slightly from ~20
      to ~10 ng L(-1). Although such concentrations are in the range allowed by the
      Water Framework Directive, they far exceed (up to 10*) the ground content ceiling
      set for 2021.

PMID- 25960272
TI  - Trace-elements, methylmercury and metallothionein levels in Magellanic penguin
      (Spheniscus magellanicus) found stranded on the Southern Brazilian coast.
AB  - Magellanic penguins have been reported as good biomonitors for several types of
      pollutants, including trace-elements. In this context, selenium (Se), total
      mercury, methylmercury, inorganic mercury (Hg(inorg)), cadmium (Cd) and lead
      (Pb), as well as metallothionein (MT) levels, were evaluated in the feathers,
      liver and kidney of juvenile Magellanic penguins found stranded along the coast
      of Southern Brazil. The highest concentrations of all trace-elements and
      methylmercury were found in internal organs. Concentrations of Cd and Se in
      feathers were extremely low in comparison with their concentrations in soft
      tissues. The results showed that both Se and MT are involved in the
      detoxification of trace-elements (Cd, Pb and Hg(inorg)) since statistically
      significant relationships were found in liver. Conversely, hepatic Se was shown
      to be the only detoxifying agent for methylmercury.

PMID- 25960273
TI  - Biogeochemistry of bulk organic matter and biogenic elements in surface sediments
      of the Yangtze River Estuary and adjacent sea.
AB  - This study investigated the distribution and roles of total organic carbon (TOC),
      biogenic silicon (BSi), various forms of nitrogen (N) and phosphorus (P), and the
      stable carbon isotope (delta(13)C) in surface sediments of the Yangtze River
      Estuary (YRE) and adjacent sea. Terrestrial input accounted for 12-63% of total
      organic matter in the study area. The distribution of biogenic elements was
      affected by the Changjiang Diluted Water, the Jiangsu Coastal Current, human
      activities, marine biological processes, and the sediment grain size. Potentially
      bioavailable N and P accounted for an average 79.6% of the total N (TN) and 31.8%
      of the total P (TP), respectively. The burial fluxes for TOC, BSi, TN and TP were
      39.74-2194.32, 17.34-517.48, 5.02-188.85 and 3.10-62.72 MUmol cm(-2) yr(-1),
      respectively. The molar ratios of total N/P (1.2-5.0), Si/P (5.0-14.8) and Fe/P
      (21-61) indicated that much of the P was sequestered in sediments.

PMID- 25960274
TI  - Sources and ecological risk assessment of PAHs in surface sediments from Bohai
      Sea and northern part of the Yellow Sea, China.
AB  - Sources and ecological risk of sixteen priority PAHs in surface sediments from
      Bohai Sea (BS) and northern part of the Yellow Sea (NPYS) were investigated. The
      total concentrations of PAHs varied in ranges 149.24-1211.81 and 148.28-907.47
      ng/g for BS and NPYS, respectively. Principal component analysis-multiple linear
      regression (PCA-MLR) suggested that coal combustion, vehicular emission and coke
      oven could be the primary PAH contributors, accounting for 56.6%, 29.2% and 14.2%
      of PAH concentrations, respectively. Analysis with sediment quality guidelines
      (SQGs) indicated that acenaphthylene, fluorene, phenanthrene, fluoranthene,
      pyrene and dibenzo(a,h)anthracene may occasionally cause adverse biological
      effects in some stations. Organic carbon (OC)-normalized analysis and mean
      effects range-median quotient (M-ERM-Q) suggested that the combined ecological
      risk of PAHs was generally low. The toxic equivalent concentrations of
      carcinogenic PAHs were 12.87-64.6 ng/g-BaP(eq) and 5.95-68.80 ng/g-BaP(eq) in BS
      and NPYS, respectively, suggesting low carcinogenic risk for both BS and NPYS.

PMID- 25960275
TI  - Biological effects of long term fine limestone tailings discharge in a fjord
      ecosystem.
AB  - Benthic infaunal data collected from 1993 to 2010 were analysed to examine the
      effect of long term discharge of fine limestone tailings on macrofaunal species
      assemblages in a fjord. Relative distance from the outfall and proportion of fine
      tailings in the sediment were correlated with benthic community structure.
      Diversity decreased with increasing proportion of fine tailings. Biological
      Traits Analysis (BTA) was used to explore the temporal and spatial effects of the
      tailings gradient on macrofaunal functional attributes. BTA revealed that all
      stations along a pressure gradient of fine limestone tailings were dominated by
      free-living species. As the proportion of fine tailings in the sediment
      increased, there was an increase in fauna that were smaller, highly mobile,
      living on or nearer the surface sediment, with shorter lifespans. There was a
      decrease in permanent tube dwellers, those fauna with low or no mobility, that
      live deeper in the sediment and have longer lifespans (>5 yrs).

PMID- 25960276
TI  - Flow cytometric applicability to evaluate UV inactivation of phytoplankton in
      marine water samples.
AB  - Disinfection of microbes is of importance to prevent the spread of pathogens and
      non-indigenous species in the environment. Here we test the applicability of
      using flow cytometry (FCM) to evaluate inactivation of the phytoplankter
      Tetraselmis suecica after UV irradiation and labeling with the esterase substrate
      5-carboxyfluorescein diacetate acetoxymethyl ester (CFDA-AM). Non-irradiated and
      UV irradiated samples were analyzed with the plate count technique and FCM for 24
      days. The numbers of colony forming units were used as a standard to develop a
      FCM protocol. Our protocol readily distinguishes live and dead cells, but
      challenges were encountered when determining whether UV damaged cells are dying
      or repairable. As damaged cells can represent a risk to aquatic organisms and/or
      humans, this was taken into account when developing the FCM protocol. In spite of
      the above mentioned challenges we argue that FCM represents an accurate and rapid
      method to analyze T. suecica samples.

PMID- 25960277
TI  - Impact of intertidal oyster trestle cultivation on the Ecological Status of
      benthic habitats.
AB  - A considerable number of Ireland's shellfish production areas co-occur with or
      are adjacent to Natura 2000 sites which are protected under European legislation.
      To investigate the general interaction between trestle oyster cultivation and the
      surrounding intertidal environment, six sites were selected within designated
      Natura 2000 sites. At each trestle site three Treatment areas were sampled. One
      Treatment area corresponded to potential impacts associated with cultivation
      activities occurring at trestle structures (designated the Trestle Treatment)
      while one Treatment area corresponded to potential impacts due to cultivation
      activities occurring along access routes (the Access Treatment). An area not
      subject to any known anthropogenic activity was used as a control (the Control
      Treatment). Potential impacts associated with Trestle Treatment areas included
      changes in sediment total organic matter (TOM) levels underneath trestles due to
      the bio-deposition of faecal/pseudofaecal material while the predominant impact
      associated with Access Treatment areas was compaction of sediments due to heavy
      vehicle traffic. In this study, macrobenthic communities at the sites were highly
      variable and exhibited low levels of diversity which prevented the detection of
      general effects of cultivation activity on community structure, diversity and
      secondary production. To overcome this variability, the Infaunal Quality Index
      (IQI) was used to assess impacts on Ecological Status (ES) of benthic communities
      (sensu Water Framework Directive). Relative to Control and Trestle Treatment
      areas, activities occurring at Access Treatment areas had a significant negative
      impact on ES. This study highlights the potential of the IQI for the management
      of aquaculture activity and provides validation for the use of the IQI in Irish
      intertidal environments. This study also highlights the IQI as a potential tool
      for assessing the conservation status of designated habitats in Natura 2000
      sites. 

PMID- 25960278
TI  - Detection of protease activity in cells and animals.
AB  - Proteases are involved in a wide variety of biologically and medically important
      events. They are entangled in a complex network of processes that regulate their
      activity, which makes their study intriguing, but challenging. For comprehensive
      understanding of protease biology and effective drug discovery, it is therefore
      essential to study proteases in models that are close to their complex native
      environments such as live cells or whole organisms. Protease activity can be
      detected by reporter substrates and activity-based probes, but not all of these
      reagents are suitable for intracellular or in vivo use. This review focuses on
      the detection of proteases in cells and in vivo. We summarize the use of probes
      and substrates as molecular tools, discuss strategies to deliver these tools
      inside cells, and describe sophisticated read-out techniques such as mass
      spectrometry and various imaging applications. This article is part of a Special
      Issue entitled: Physiological Enzymology and Protein Functions. 

PMID- 25960279
TI  - Discovery of compounds that protect tyrosine hydroxylase activity through
      different mechanisms.
AB  - Pharmacological chaperones are small compounds that correct the folding of mutant
      proteins, and represent a promising therapeutic strategy for misfolding diseases.
      We have performed a screening of 10,000 compounds searching for pharmacological
      chaperones of tyrosine hydroxylase (TH), the tetrahydrobiopterin (BH4)-dependent
      enzyme that catalyzes the rate-limiting step in the synthesis of catecholamines.
      A large number of compounds bound to human TH, isoform 1 (hTH1), but only twelve
      significantly protected wild-type (hTH1-wt) and mutant TH-R233H (hTH1-p.R202H),
      associated to the rare neurological disorder TH deficiency (THD), from time
      dependent loss of activity. Three of them (named compounds 2, 4 and 5) were
      subjected to detailed characterization of their functional and molecular effects.
      Whereas compounds 2 and 4 had a characteristic pharmacological chaperone
      (stabilizing) effect, compound 5 protected the activity in a higher extent than
      expected from the low conformational stabilization exerted on hTH1. Compounds 4
      and 5 were weak competitive inhibitors with respect to the cofactor BH4 and, as
      seen by electron paramagnetic resonance, they induced small changes to the first
      coordination sphere of the catalytic iron. Molecular docking also indicated
      active-site location with coordination to the iron through a pyrimidine nitrogen
      atom. Interestingly, compound 5 increased TH activity in cells transiently
      transfected with either hTH1-wt or the THD associated mutants p.L205P, p.R202H
      and p.Q381K without affecting the steady-state TH protein levels. This work
      revealed different mechanisms for the action of pharmacological chaperones and
      identifies a subtype of compounds that preserve TH activity by weak binding to
      the catalytic iron. This article is part of a Special Issue entitled: Cofactor
      dependent proteins: Evolution, chemical diversity and bio-applications. 

PMID- 25960280
TI  - Insights into the Hendra virus NTAIL-XD complex: Evidence for a parallel
      organization of the helical MoRE at the XD surface stabilized by a combination of
      hydrophobic and polar interactions.
AB  - The Hendra virus is a member of the Henipavirus genus within the Paramyxoviridae
      family. The nucleoprotein, which consists of a structured core and of a C
      terminal intrinsically disordered domain (N(TAIL)), encapsidates the viral genome
      within a helical nucleocapsid. N(TAIL) partly protrudes from the surface of the
      nucleocapsid being thus capable of interacting with the C-terminal X domain (XD)
      of the viral phosphoprotein. Interaction with XD implies a molecular recognition
      element (MoRE) that is located within N(TAIL) residues 470-490, and that
      undergoes alpha-helical folding. The MoRE has been proposed to be embedded in the
      hydrophobic groove delimited by helices alpha2 and alpha3 of XD, although
      experimental data could not discriminate between a parallel and an antiparallel
      orientation of the MoRE. Previous studies also showed that if the binding
      interface is enriched in hydrophobic residues, charged residues located close to
      the interface might play a role in complex formation. Here, we targeted for site
      directed mutagenesis two acidic and two basic residues within XD and N(TAIL). ITC
      studies showed that electrostatics plays a crucial role in complex formation and
      pointed a parallel orientation of the MoRE as more likely. Further support for a
      parallel orientation was afforded by SAXS studies that made use of two chimeric
      constructs in which XD and the MoRE were covalently linked to each other.
      Altogether, these studies unveiled the multiparametric nature of the interactions
      established within this complex and contribute to shed light onto the molecular
      features of protein interfaces involving intrinsically disordered regions.

PMID- 25960281
TI  - Management of an expansile orbital mass: Plexiform neurofibroma decompression by
      orbitozygomatic approach.
AB  - Neurofibromatosis types 1 (NF-1) and 2 are significant entities to
      otolaryngologists because they frequently involve head and neck skin, brain,
      skull base, orbits, and surrounding neural and vascular structures. We present
      the case of a 52-year-old male with progressive, marked unilateral proptosis due
      to a multilobulated orbital mass, secondary to biopsy-proven plexiform
      neurofibroma (PN). Acute worsening of proptosis leading to corneal abrasion,
      diplopia, and pain required debulking surgery, for which an orbitozygomatic
      approach was utilized. Genetic testing for NF-1 revealed no mutation. This rare
      case of NF-negative orbital PN and multidisciplinary treatment considerations for
      expansile orbital tumors are discussed.

PMID- 25960282
TI  - The development of cisplatin resistance in neuroblastoma is accompanied by
      epithelial to mesenchymal transition in vitro.
AB  - Neuroblastoma is a challenging childhood malignancy, with a very high percentage
      of patients relapsing following acquisition of drug resistance, thereby
      necessitating the identification of mechanisms of drug resistance as well as new
      biological targets contributing to the aggressive pathogenicity of the disease.
      In order to investigate the molecular pathways that are involved with drug
      resistance in neuroblastoma, we have developed and characterised cisplatin
      resistant sublines SK-N-ASCis24, KellyCis83 and CHP-212Cis100, integrating data
      of cell behaviour, cytotoxicity, genomic alterations and modulation of protein
      expression. All three cisplatin resistant cell lines demonstrated cross
      resistance to temozolomide, etoposide and irinotecan, all of which are drugs in
      re-initiation therapy. Array CGH analysis indicated that resistant lines have
      acquired additional genomic imbalances. Differentially expressed proteins were
      identified by mass spectrometry and classified by bioinformatics tools according
      to their molecular and cellular functions and their involvement into biological
      pathways. Significant changes in the expression of proteins involved with
      pathways such as actin cytoskeletal signalling (p = 9.28E-10), integrin linked
      kinase (ILK) signalling (p = 4.01E-8), epithelial adherens junctions signalling
      (p = 5.49E-8) and remodelling of epithelial adherens junctions (p = 5.87E-8)
      pointed towards a mesenchymal phenotype developed by cisplatin resistant SK-N
      ASCis24. Western blotting and confocal microscopy of MYH9, ACTN4 and ROCK1
      coupled with invasion assays provide evidence that elevated levels of MYH9 and
      ACTN4 and reduced levels of ROCK1 contribute to the increased ROCK1-independent
      migratory potential of SK-N-ASCis24. Therefore, our results suggest that
      epithelial-to-mesenchymal transition is a feature during the development of drug
      resistance in neuroblastoma. 

PMID- 25960283
TI  - Pregnancy with a pinhole introitus: A report of two cases and a review of the
      literature.
AB  - OBJECTIVES: As over 125 million women worldwide have undergone female genital
      mutilation (FGM), 170,000 of whom are estimated to live in the UK alone,
      obstetricians and gynaecologists need to be aware of the grades and consequences
      of this devastating condition. Women with type III FGM, even when they are unable
      to have penetrative intercourse, can conceive, and obstetricians should be aware
      of this to ensure optimal care of these patients. To determine the most
      appropriate surgical approach, deinfibulation in pregnancy should follow some
      basic principles which take into account the psychological needs of women as well
      as the extent of scarring. CASES: We present two cases of women who had never
      engaged in penetrative intercourse and therefore presented with no knowledge that
      they were pregnant. They underwent antenatal deinfibulation and subsequent
      management based on individual request. CONCLUSIONS: Management in pregnancy can
      pose particular problems and should be individualised. In all childbearing women
      with FGM, even where intercourse has not been possible, pregnancy should be
      considered. Clinicians should be aware of the types of FGM and management should
      be undertaken by a designated clinician with appropriate expertise. Pregnant
      women who have undergone FGM should be examined to identify the requirement for
      antenatal surgical correction.

PMID- 25960285
TI  - Synthesis of 4(3H)quinazolinimines by reaction of (E)-N-(aryl)-acetimidoyl or 
      benzimidoyl chloride with amines.
AB  - An efficient one-step method to access 4(3H)quinazolinimines by reaction of
      phenylchloroimines with 2-aminobenzonitrile is described. The reaction of (E)-N
      (2-cyanophenyl)benzimidoyl chloride with substituted anilines that yields a
      number of their corresponding C2, N3-substituted quinazoliniminium chlorides or
      neutral products is also reported. These methods provide direct and flexible
      access to diverse substituted iminoquinazolines substituted at the C2, N3
      positions. All the new compounds were fully characterized and six examples are
      given with their single-crystal X-ray structure. 

PMID- 25960284
TI  - Clinical Efficacy of Andrographolide Sulfonate in the Treatment of Severe Hand,
      Foot, and Mouth Disease (HFMD) is Dependent upon Inhibition of Neutrophil
      Activation.
AB  - Andrographolide sulfonate treatment has been shown to improve clinical severe
      hand, foot, and mouth disease (HFMD) efficacies when combined with conventional
      therapy. However, the mechanisms for its therapeutic effects remain elusive. In
      this study, we aimed to investigate whether andrographolide sulfonate exerts its
      efficacy by acting on neutrophil activation. We obtained serial plasma samples at
      two time points (before and after 5 days of therapy) from 28 HFMD patients who
      received conventional therapy and 18 patients who received combination therapy
      (andrographolide sulfonate plus conventional therapy). Then, we measured plasma
      myeloperoxidase (MPO), S100A8/A9, histone, and inflammatory cytokine levels.
      Furthermore, we examined if andrographolide sulfonate had direct effects on
      neutrophil activation in vitro. We observed that MPO and S100A8/A9 levels were
      markedly elevated in the HFMD patients before clinical treatment. At 5 days post
      medication, the MPO, S100A8/A9, histone, and interleukin-6 levels were markedly
      lower in the combination therapy group compared with the conventional therapy
      group. In vitro studies showed that andrographolide sulfonate inhibited
      lipopolysaccharide-stimulated neutrophil activation, demonstrated by the
      decreased production of reactive oxygen species and cytokines. These data
      indicate that neutrophil activation modulation by andrographolide sulfonate may
      be a critical determinant for its clinical HFMD treatment efficacy. Copyright (c)
      2015 John Wiley & Sons, Ltd. 

PMID- 25960286
TI  - Digestive proteases in bodies and faeces of the two-spotted spider mite,
      Tetranychus urticae.
AB  - Digestive proteases of the phytophagous mite Tetranychus urticae have been
      characterised by comparing their activity in body and faecal extracts. Aspartyl,
      cathepsin B- and L-like and legumain activities were detected in both mite bodies
      and faeces, with a specific activity of aspartyl and cathepsin L-like proteases
      about 5- and 2-fold higher, respectively, in mite faeces than in bodies. In
      general, all these activities were maintained independently of the host plant
      where the mites were reared (bean, tomato or maize). Remarkably, this is the
      first report in a phytophagous mite of legumain-like activity, which was
      characterised for its ability to hydrolyse the specific substrate Z-VAN-AMC, its
      activation by DTT and inhibition by IAA but not by E-64. Gel free nanoLC-nanoESI
      QTOF MS/MS proteomic analysis of mite faeces resulted in the identification of
      four cathepsins L and one aspartyl protease (from a total of the 29 cathepsins L,
      27 cathepsins B, 19 legumains and two aspartyl protease genes identified the
      genome of this species). Gene expression analysis reveals that four cathepsins L
      and the aspartyl protease identified in the mite faeces, but also two cathepsins
      B and two legumains that were not detected in the faeces, were expressed at high
      levels in the spider mite feeding stages (larvae, nymphs and adults) relative to
      embryos. Taken together, these results indicate a digestive role for cysteine and
      aspartyl proteases in T. urticae. The expression of the cathepsins B and L,
      legumains and aspartyl protease genes analysed in our study increased in female
      adults after feeding on Arabidopsis plants over-expressing the HvCPI-6 cystatin,
      that specifically targets cathepsins B and L, or the CMe trypsin inhibitor that
      targets serine proteases. This unspecific response suggests that in addition to
      compensation for inhibitor-targeted enzymes, the increase in the expression of
      digestive proteases in T. urticae may act as a first barrier against ingested
      plant defensive proteins. 

PMID- 25960287
TI  - Treatment of Sezary Syndrome With Alemtuzumab: A Series of 5 Cases and a Review
      of the Literature.
AB  - Alemtuzumab is a monoclonal antibody that has been used to treat refractory cases
      of Sezary syndrome (SS) and advanced mycosis fungoides. We present 5 patients
      with SS who were treated with alemtuzumab between 2008 and 2012, with an overall
      response rate of 80% (40% partial response and 40% complete response). A regimen
      of 10mg administered subcutaneously was well tolerated with acceptable toxicity.
      The median duration of response was 13 months. However, one patient remains in
      complete remission after 67 months, a remarkable outcome given the low survival
      rate associated with SS. In conclusion, we believe that alemtuzumab may be useful
      in cases of SS refractory to other treatments. As there are no curative
      treatments for SS, alemtuzumab should be considered as a therapeutic option. 

PMID- 25960288
TI  - Electrical conductivity in two mixed-valence liquids.
AB  - Two different room-temperature liquid systems were investigated, both of which
      conduct a DC electrical current without decomposition or net chemical
      transformation. DC electrical conductivity is possible in both cases because of
      the presence of two different oxidation states of a redox-active species. One
      system is a 1 : 1 molar mixture of n-butylferrocene (BuFc) and its cation
      bis(trifluoromethane)sulfonimide salt, [BuFc(+)][NTf2(-)], while the other is a 1
      : 1 molar mixture of TEMPO and its cation bis(trifluoromethane)sulfonimide salt,
      [TEMPO(+)][NTf2(-)]. The TEMPO-[TEMPO(+)][NTf2(-)] system is notable in that it
      is an electrically conducting liquid in which the conductivity originates from an
      organic molecule in two different oxidation states, with no metals present.
      Single-crystal X-ray diffraction of [TEMPO(+)][NTf2(-)] revealed a complex
      structure with structurally different cation-anion interactions for cis- and
      trans [NTf2(-)] conformers. The electron transfer self-exchange rate constant for
      BuFc/BuFc(+) in CD3CN was determined by (1)H NMR spectroscopy to be 5.4 * 10(6)
      M(-1) s(-1). The rate constant allowed calculation of an estimated electrical
      conductivity of 7.6 * 10(-5)Omega(-1) cm(-1) for BuFc-[BuFc(+)][NTf2(-)], twice
      the measured value of 3.8 * 10(-5)Omega(-1) cm(-1). Similarly, a previously
      reported self-exchange rate constant for TEMPO/TEMPO(+) in CH3CN led to an
      estimated conductivity of 1.3 * 10(-4)Omega(-1) cm(-1) for TEMPO-[TEMPO(+)][NTf2(
      )], a factor of about 3 higher than the measured value of 4.3 * 10(-5)Omega(-1)
      cm(-1). 

PMID- 25960289
TI  - Pushing Up Lithium Storage through Nanostructured Polyazaacene Analogues as
      Anode.
AB  - According to the evidence from both theoretical calculations and experimental
      findings, conjugated ladder polymers containing large pi-conjugated structure, a
      high number of nitrogen heteroatoms, and a multiring aromatic system, could be an
      ideal organic anode candidate for lithium-ion batteries (LIBs). In this report,
      we demonstrated that the nanostructured polyazaacene analogue poly(1,6
      dihydropyrazino[2,3g]quinoxaline-2,3,8-triyl-7-(2H)-ylidene-7,8-dimethylidene)
      (PQL) shows high performance as anode materials in LIBs: high capacity (1750 mAh
      g(-1), 0.05C), good rate performance (303 mAh g(-1), 5C), and excellent cycle
      life (1000 cycles), especially at high temperature of 50  degrees C. Our results
      suggest nanostructured conjugated ladder polymers could be alternative electrode
      materials for the practical application of LIBs.

PMID- 25960290
TI  - Dual redox catalysts for oxygen reduction and evolution reactions: towards a
      redox flow Li-O2 battery.
AB  - A redox flow lithium-oxygen battery (RFLOB) by using soluble redox catalysts with
      good performance was demonstrated for large-scale energy storage. The new device
      enables the reversible formation and decomposition of Li2O2 via redox targeting
      reactions in a gas diffusion tank, spatially separated from the electrode, which
      obviates the passivation and pore clogging of the cathode.

PMID- 25960292
TI  - Inhibition of miR-146b expression increases radioiodine-sensitivity in poorly
      differential thyroid carcinoma via positively regulating NIS expression.
AB  - Dedifferentiated thyroid carcinoma (DTC) with the loss of radioiodine uptake
      (RAIU) is often observed in clinical practice under radioiodine therapy,
      indicating the challenge for poor prognosis. MicroRNA (miRNA) has emerged as a
      promising therapeutic target in many diseases; yet, the role of miRNAs in RAIU
      has not been generally investigated. Based on recent studies about miRNA
      expression in papillary or follicular thyroid carcinomas, the expression profiles
      of several thyroid relative miRNAs were investigated in one DTC cell line,
      derived from normal DTC cells by radioiodine treatment. The top candidate miR
      146b, with the most significant overexpression profiles in dedifferentiated
      cells, was picked up. Further research found that miR-146b could be negatively
      regulated by histone deacetylase 3 (HDAC3) in normal cells, indicating the
      correlation between miR-146b and Na(+)/I(-) symporter (NIS)-mediated RAIU.
      Fortunately, it was confirmed that miR-146b could regulate NIS
      expression/activity; what is more important, miR-146b interference would
      contribute to the recovery of radioiodine-sensitivity in dedifferentiated cells
      via positively regulating NIS. In the present study, it was concluded that NIS
      mediated RAIU could be modulated by miR-146b; accordingly, miR-146b might serve
      as one of targets to enhance efficacy of radioactive therapy against poorly
      differential thyroid carcinoma (PDTC). 

PMID- 25960293
TI  - Hibernation-specific alternative splicing of the mRNA encoding cold-inducible RNA
      binding protein in the hearts of hamsters.
AB  - The hearts of hibernating animals are capable of maintaining constant beating
      despite a decrease in body temperature to less than 10  degrees C during
      hibernation, suggesting that the hearts of hibernators are highly tolerant to a
      cold temperature. In the present study, we examined the expression pattern of
      cold-inducible RNA-binding protein (CIRP) in the hearts of hibernating hamsters,
      since CIRP plays important roles in protection of various types of cells against
      harmful effects of cold temperature. RT-PCR analysis revealed that CIRP mRNA is
      constitutively expressed in the heart of a non-hibernating euthermic hamster with
      several different forms probably due to alternative splicing. The short product
      contained the complete open reading frame for full-length CIRP. On the other
      hand, the long product had inserted sequences containing a stop codon, suggesting
      production of a C-terminal deletion isoform of CIRP. In contrast to non
      hibernating hamsters, only the short product was amplified in hibernating
      animals. Induction of artificial hypothermia in non-hibernating hamsters did not
      completely mimic the splicing patterns observed in hibernating animals, although
      a partial shift from long form mRNA to short form was observed. Our results
      indicate that CIRP expression in the hamster heart is regulated at the level of
      alternative splicing, which would permit a rapid increment of functional CIRP
      when entering hibernation. 

PMID- 25960291
TI  - Costs of complications after colorectal cancer surgery in the Netherlands:
      Building the business case for hospitals.
AB  - BACKGROUND: Healthcare providers worldwide are struggling with rising costs while
      hospitals budgets are under stress. Colorectal cancer surgery is commonly
      performed, however it is associated with a disproportionate share of adverse
      events in general surgery. Since adverse events are associated with extra
      hospital costs it seems important to explicitly discuss the costs of
      complications and the risk factors for high-costs after colorectal surgery.
      METHODS: Retrospective analysis of clinical and financial outcomes after
      colorectal cancer surgery in 29 Dutch hospitals (6768 patients). Detailed
      clinical data was derived from the 2011-2012 population-based Dutch Surgical
      Colorectal Audit database. Costs were measured uniform in all participating
      hospitals and based on Time-Driven Activity-Based Costing. FINDINGS: Of total
      hospital costs in this study, 31% was spent on complications and the top 5% most
      expensive patients were accountable for 23% of hospitals budgets. Minor and
      severe complications were respectively associated with a 26% and 196% increase in
      costs as compared to patients without complications. Independent from other risk
      factors, ASA IV, double tumor, ASA III, short course preoperative radiotherapy
      and TNM-4 stadium disease were the top-5 attributors to high costs. CONCLUSIONS:
      This article shows that complications after colorectal cancer surgery are
      associated with a substantial increase in costs. Although not all surgical
      complications can be prevented, reducing complications will result in
      considerable cost savings. By providing a business case we show that investments
      made to develop targeted quality improvement programs will pay off eventually.
      Results based on this study should encourage healthcare providers to endorse
      quality improvement efforts.

PMID- 25960294
TI  - Role of Aquaporin 0 in lens biomechanics.
AB  - Maintenance of proper biomechanics of the eye lens is important for its
      structural integrity and for the process of accommodation to focus near and far
      objects. Several studies have shown that specialized cytoskeletal systems such as
      the beaded filament (BF) and spectrin-actin networks contribute to mammalian lens
      biomechanics; mutations or deletion in these proteins alters lens biomechanics.
      Aquaporin 0 (AQP0), which constitutes ~45% of the total membrane proteins of lens
      fiber cells, has been shown to function as a water channel and a structural cell
      to-cell adhesion (CTCA) protein. Our recent ex vivo study on AQP0 knockout (AQP0
      KO) mouse lenses showed the CTCA function of AQP0 could be crucial for
      establishing the refractive index gradient. However, biomechanical studies on the
      role of AQP0 are lacking. The present investigation used wild type (WT), AQP5 KO
      (AQP5(-/-)), AQP0 KO (heterozygous KO: AQP0(+/-); homozygous KO: AQP0(-/-); all
      in C57BL/6J) and WT-FVB/N mouse lenses to learn more about the role of fiber cell
      AQPs in lens biomechanics. Electron microscopic images exhibited decreases in
      lens fiber cell compaction and increases in extracellular space due to deletion
      of even one allele of AQP0. Biomechanical assay revealed that loss of one or both
      alleles of AQP0 caused a significant reduction in the compressive load-bearing
      capacity of the lenses compared to WT lenses. Conversely, loss of AQP5 did not
      alter the lens load-bearing ability. Compressive load-bearing at the suture area
      of AQP0(+/-) lenses showed easy separation while WT lens suture remained intact.
      These data from KO mouse lenses in conjunction with previous studies on lens
      specific BF proteins (CP49 and filensin) suggest that AQP0 and BF proteins could
      act co-operatively in establishing normal lens biomechanics. We hypothesize that
      AQP0, with its prolific expression at the fiber cell membrane, could provide
      anchorage for cytoskeletal structures like BFs and together they help to confer
      fiber cell shape, architecture and integrity. To our knowledge, this is the first
      report identifying the involvement of an aquaporin in lens biomechanics. Since
      accommodation is required in human lenses for proper focusing, alteration in the
      adhesion and/or water channel functions of AQP0 could contribute to presbyopia. 

PMID- 25960295
TI  - Novel sex-dependent differentially methylated regions are demethylated in adult
      male mouse livers.
AB  - In mammalian livers, sexual dimorphisms are observed in tissue-specific functions
      and diseases such as hepatocellular carcinoma. We identified sex-dependent
      differentially methylated regions (S-DMRs) which had been previously been
      characterized as growth hormone- STAT5 dependent. In this study, we performed
      genome-wide screening and identified ten additional hypomethylated S-DMR gene
      regions in male livers. Of these S-DMRs, Uggt2 and Sarnp were hypomethylated in
      both male and female livers compared to brain and embryonic stem (ES) cells.
      Similarly, Adam2, Uggt2, and Scp2 were hypomethylated in female embryonic germ
      (EG) cells and not in male EG cells, indicating that these S-DMRs are liver
      specific male hypo-S-DMRs. Interestingly, the five S-DMRs were free from STAT5
      chromatin immunoprecipitation (ChIP) signals, suggesting that S-DMRs are
      independent of the growth hormone-STAT5-pathway. Instead, the DNA methylation
      statuses of the S-DMRs of Adam2, Snx29, Uggt2, Sarnp, and Rnpc3 genes were under
      the control of testosterone. Importantly, the hypomethylated S-DMRs of the Adam2
      and Snx29 regions showed chromatin decondensation. Epigenetic factors could be
      responsible for the sexual dimorphisms in DNA methylation status and chromatin
      structure, as the expression of Dnmt1, Dnmt3b, and Tet2 genes was lower in male
      mice compared to female mice and TET2 expression recovered following orchidectomy
      by testosterone treatment. In conclusion, we identified novel male-specific
      hypomethylated S-DMRs that contribute to chromatin decondensation in the liver. S
      DMRs were tissue-specific and the hypomethylation is testosterone-dependent. 

PMID- 25960296
TI  - Identification and characterization of a nuclear localization signal of TRIM28
      that overlaps with the HP1 box.
AB  - Tripartite motif-containing 28 (TRIM28) is a transcription regulator, which forms
      a repressor complex containing heterochromatin protein 1 (HP1). Here, we report
      identification of a nuclear localization signal (NLS) within the 462-494 amino
      acid region of TRIM28 that overlaps with its HP1 binding site, HP1 box. GST
      pulldown experiments revealed the interaction of the arginine-rich TRIM28 NLS
      with various importin alpha subtypes (alpha1, alpha2 and alpha4). In vitro
      transport assay demonstrated that nuclear localization of GFP-TRIM28 NLS is
      mediated by importin alphas, in conjunction with importin beta1 and Ran. Further,
      we demonstrated that HP1 and importin alphas compete for binding to TRIM28.
      Together, our findings suggest that importin alpha has an essential role in the
      nuclear delivery and preferential HP1 interaction of TRIM28. 

PMID- 25960297
TI  - Recognition of chromatin by the plant alkaloid, ellipticine as a dual binder.
AB  - Recognition of core histone components of chromatin along with chromosomal DNA by
      a class of small molecule modulators is worth examining to evaluate their
      intracellular mode of action. A plant alkaloid ellipticine (ELP) which is a
      putative anticancer agent has so far been reported to function via DNA
      intercalation, association with topoisomerase II and binding to telomere region.
      However, its effect upon the potential intracellular target, chromatin is
      hitherto unreported. Here we have characterized the biomolecular recognition
      between ELP and different hierarchical levels of chromatin. The significant
      result is that in addition to DNA, it binds to core histone(s) and can be
      categorized as a 'dual binder'. As a sequel to binding with histone(s) and core
      octamer, it alters post-translational histone acetylation marks. We have further
      demonstrated that it has the potential to modulate gene expression thereby
      regulating several key biological processes such as nuclear organization,
      transcription, translation and histone modifications. 

PMID- 25960298
TI  - N-Glycosylation modulates filopodia-like protrusions induced by sez-6 through
      regulating the distribution of this protein on the cell surface.
AB  - Seizure-related gene 6 (sez-6) is a trans-membrane protein expressed by neuronal
      cells that modulates dendritic branching. It has three clusters of eleven
      possible N-glycosylation sites in the extracellular domain region: sugar chain
      (SC)1-3, SC4-7, and SC8-11. Recent reports suggest that N-glycosylation modulates
      the membrane trafficking and function of trans-membrane proteins. Here, we
      studied the role of N-glycosylation in sez-6 function. We transfected mutants
      lacking one, two, or all N-glycosylation clusters into neuro2a cells. A mutant
      lacking all N-glycosylation was transported to the cell membrane. Mutants lacking
      one cluster (sez-6 DeltaSC1-3, DeltaSC4-7, DeltaSC8-11) were evenly distributed
      on the cell membrane and secreted into the conditioned medium, as in wild-type
      sez-6; in contrast, the unglycosylated mutant, sez-6 DeltaSC1-11, and mutants
      having only one cluster (sez-6 SC1-3, SC8-11) were localized in some portions on
      the cell membrane. Despite sez-6 SC4-7 having only one cluster, it was
      transported like the wild type. Among mutants behaving like the wild type, sez-6
      DeltaSC1-3 and DeltaSC4-7 reduced neurite formation. Interestingly, mutants
      lacking SC4-7 (sez-6 DeltaSC4-7) did not affect the formation of filopodia-like
      protrusions. In contrast, other mutants as well as the wild type induced it,
      suggesting that SC4-7 is crucial for filopodia-like protrusions. Our results
      indicate that N-glycosylation regulates cell morphology through modulating the
      cell surface distribution of sez-6 protein. 

PMID- 25960300
TI  - (R)evolution in the Management of Acute Kidney Injury in Newborns.
AB  - The application of continuous renal replacement therapy (CRRT) in children,
      before roller pumps and dialysis monitors were available in the intensive care
      unit, was realized by continuous arteriovenous hemofiltration. Then
      hemofiltration was coupled with dialysis in order to increase dialytic dose and
      system efficiency, and the circuit and filters were specifically modified to
      optimize patency and session life span. After about 30 years, another revolution
      is ongoing, in that pediatric acute kidney injury (AKI) and fluid accumulation
      (for which critically ill newborns and children with multiple-organ dysfunction
      are greatly at risk) are recognized as independently associated with mortality
      and identified as primary conditions to prevent and aggressively treat. Today,
      novel technology specifically dedicated for very young patients will allow
      feasible and straightfoward application of CRRT to infants and children. This
      article discusses the authors' personal perspectives on how clinical and
      technical issues of dialysis in children have been addressed and how today,
      severe pediatric AKI can be managed with accurate and safe CRRT machines that
      will likely yield outcome improvements in the coming decades.

PMID- 25960301
TI  - Metformin Use in Type 2 Diabetes Mellitus With CKD: Is It Time to Liberalize
      Dosing Recommendations?

PMID- 25960299
TI  - Calciphylaxis: risk factors, diagnosis, and treatment.
AB  - Calciphylaxis is a rare but devastating condition that has continued to challenge
      the medical community since its early descriptions in the scientific literature
      many decades ago. It is predominantly seen in patients with chronic kidney
      failure treated with dialysis (uremic calciphylaxis) but is also described in
      patients with earlier stages of chronic kidney disease and with normal kidney
      function. In this review, we discuss the available medical literature regarding
      risk factors, diagnosis, and treatment of both uremic and nonuremic
      calciphylaxis. High-quality evidence for the evaluation and management of
      calciphylaxis is lacking at this time due to its rare incidence and poorly
      understood pathogenesis and the relative paucity of collaborative research
      efforts. We hereby provide a summary of recommendations developed by a
      multidisciplinary team for patients with calciphylaxis. 

PMID- 25960302
TI  - Total Kidney Volume in Autosomal Dominant Polycystic Kidney Disease: A Biomarker
      of Disease Progression and Therapeutic Efficacy.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is the most common
      potentially life-threatening monogenic disorder in humans, characterized by
      progressive development and expansion of fluid-filled cysts in the kidneys and
      other organs. Ongoing cyst growth leads to progressive kidney enlargement,
      whereas kidney function remains stable for decades as a result of hyperfiltration
      and compensation by unaffected nephrons. Kidney function irreversibly declines
      only in the late stages of the disease, when most of the parenchyma is lost to
      cystic and fibrotic tissue and the remaining compensatory capacity is
      overwhelmed. Hence, conventional kidney function measures, such as glomerular
      filtration rate, do not adequately assess disease progression in ADPKD,
      especially in its early stages. Given the recent development of potential
      targeted therapies in ADPKD, it has become critically important to identify
      relevant biomarkers that can be used to determine the degree of disease
      progression and evaluate the effects of therapeutic interventions on the course
      of the disease. We review the current evidence to provide an informed perspective
      on whether total kidney volume (TKV) is a suitable biomarker for disease
      progression and whether TKV can be used as an efficacy end point in clinical
      trials. We conclude that because cystogenesis is the central factor leading to
      kidney enlargement, TKV appears to be an appropriate biomarker and is gaining
      wider acceptance. Several studies have identified TKV as a relevant imaging
      biomarker for monitoring and predicting disease progression and support its use
      as a prognostic end point in clinical trials. 

PMID- 25960303
TI  - Effect of Moderate Aerobic Exercise Training on Endothelial Function and Arterial
      Stiffness in CKD Stages 3-4: A Randomized Controlled Trial.
AB  - BACKGROUND: Evidence of a beneficial effect of exercise training on mediators of
      vascular disease is accumulating in chronic kidney disease (CKD), but its effect
      on vascular function in vivo still has to be established. The present study was
      designed to investigate whether a formal aerobic exercise training program
      improves peripheral endothelial function in patients with CKD stages 3 to 4.
      STUDY DESIGN: Randomized controlled trial with a parallel-group design. SETTING &
      PARTICIPANTS: 48 patients with CKD stages 3 to 4 without established
      cardiovascular disease were randomly assigned to either an exercise training
      program or usual care. 40 patients completed the study (exercise training, 19;
      usual care, 21). INTERVENTION: The 3-month home-based aerobic training program
      consisted of 4 daily cycling sessions of 10 minutes each at a target heart rate,
      calculated as 90% of the heart rate achieved at the anaerobic threshold. Patients
      in the usual-care group were given standard therapy. OUTCOMES: The primary
      outcome was peripheral endothelial function. Secondary outcomes were aerobic
      capacity, arterial stiffness, numbers of endothelial (EPCs) and osteogenic
      progenitor cells (OPCs), migratory function of circulatory angiogenic cells, and
      health-related quality of life. MEASUREMENTS: Endothelial function was assessed
      with flow-mediated dilation of the brachial artery, aerobic capacity by peak
      oxygen uptake (VO(2peak)), arterial stiffness by carotid-femoral pulse wave
      velocity, numbers of EPCs and OPCs by flow cytometry, circulatory angiogenic cell
      function by an in vitro migratory assay, and quality of life by the Kidney
      Disease Quality of Life-Short Form questionnaire. RESULTS: Exercise training
      significantly improved VO(2peak) and quality of life, but not in vivo vascular
      function (flow-mediated dilation and carotid-femoral pulse wave velocity) or
      cellular markers for vascular function (EPC and OPC count and circulatory
      angiogenic cell migratory function). LIMITATIONS: Short duration and intermittent
      nature of the exercise intervention. CONCLUSIONS: In patients with CKD stages 3
      to 4 without overt cardiovascular disease, 3 months of aerobic exercise training
      improved VO(2peak) and quality of life, without altering endothelial function or
      arterial stiffness.

PMID- 25960304
TI  - Kidney Disease End Points in a Pooled Analysis of Individual Patient-Level Data
      From a Large Clinical Trials Program of the Dipeptidyl Peptidase 4 Inhibitor
      Linagliptin in Type 2 Diabetes.
AB  - BACKGROUND: Although assessment of cardiovascular safety is mandated by
      regulatory agencies for the development of new drugs to treat type 2 diabetes,
      evaluation of their renal safety has been relatively neglected. STUDY DESIGN:
      Individual patient-level data pooled analysis of 13 phase 2 or 3 randomized,
      double-blind, placebo-controlled, clinical trials of the dipeptidyl peptidase 4
      inhibitor linagliptin. SETTING & PARTICIPANTS: Participants who participated in
      any of 13 randomized clinical trials and fulfilled predefined inclusion/exclusion
      criteria, such as being drug-naive (hemoglobin A1c, 7.0%-11.0% [53-97 mmol/mol])
      or being on background glucose-lowering therapy (hemoglobin A1c, 6.5%-10.5% [48
      91 mmol/mol]). INTERVENTION: Of 5,466 consenting individuals with inadequately
      controlled type 2 diabetes, 3,505 received linagliptin, 5mg/d, and 1,961 received
      placebo. OUTCOMES: The primary kidney disease outcome was defined as first
      occurrence during the study of 6 predefined safety end points: new onset of
      moderate elevation of albuminuria (urinary albumin-creatinine ratio [ACR] >30
      mg/g with baseline values <= 30 mg/g), new onset of severe elevation of
      albuminuria (ACR > 300 mg/g with baseline values <= 300 mg/g), reduction in
      kidney function (serum creatinine increase to >=250 MUmol/L from a baseline value
      <250 MUmol/L), halving of estimated glomerular filtration rate (loss of baseline
      eGFR >50%), acute renal failure (ascertained from diagnostic codes), or death
      from any cause. MEASUREMENTS: Albuminuria was assessed using ACR. GFR was
      estimated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration)
      equation. RESULTS: Cumulative exposure (person-years) was 1,751 for linagliptin
      and 1,055 for placebo. The primary composite outcome occurred in 448 (12.8%) and
      306 (15.6%) participants in the linagliptin and placebo groups, respectively.
      Linagliptin treatment significantly reduced the hazard of kidney disease events
      by 16% compared with placebo (HR, 0.84; 95% CI, 0.72-0.97; P=0.02). LIMITATIONS:
      Retrospective and hypothesis-generating study involving short- to midterm
      clinical trials. CONCLUSIONS: Linagliptin was not associated with increased
      kidney disease risk in patients with type 2 diabetes. The potential of this drug
      to improve kidney disease outcomes warrants further investigation.

PMID- 25960305
TI  - Introduction.

PMID- 25960306
TI  - DNA-Grafted Supramolecular Polymers: Helical Ribbon Structures Formed by Self
      Assembly of Pyrene-DNA Chimeric Oligomers.
AB  - The controlled arraying of DNA strands on adaptive polymeric platforms remains a
      challenge. Here, the noncovalent synthesis of DNA-grafted supramolecular polymers
      from short chimeric oligomers is presented. The oligomers are composed of an
      oligopyrenotide strand attached to the 5'-end of an oligodeoxynucleotide. The
      supramolecular polymerization of these oligomers in an aqueous medium leads to
      the formation of one-dimensional (1D) helical ribbon structures. Atomic force and
      transmission electron microscopy show rod-like polymers of several hundred
      nanometers in length. DNA-grafted polymers of the type described herein will
      serve as models for the development of structurally and functionally diverse
      supramolecular platforms with applications in materials science and diagnostics. 

PMID- 25960308
TI  - WITHDRAWN: The first mental health law of China.
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.ajp.2014.11.001. 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- 25960309
TI  - Chirality transfer from gold nanocluster to adsorbate evidenced by vibrational
      circular dichroism.
AB  - The transfer of chirality from one set of molecules to another is fundamental for
      applications in chiral technology and has likely played a crucial role for
      establishing homochirality on earth. Here we show that an intrinsically chiral
      gold cluster can transfer its handedness to an achiral molecule adsorbed on its
      surface. Solutions of chiral Au38(2-PET)24 (2-PET=2-phenylethylthiolate) cluster
      enantiomers show strong vibrational circular dichroism (VCD) signals in
      vibrations of the achiral adsorbate. Density functional theory (DFT) calculations
      reveal that 2-PET molecules adopt a chiral conformation. Chirality transfer from
      the cluster to the achiral adsorbate is responsible for the preference of one of
      the two mirror images. Intermolecular interactions between the adsorbed molecules
      on the crowded cluster surface seem to play a dominant role for the phenomena.
      Such chirality transfer from metals to adsorbates likely plays an important role
      in heterogeneous enantioselective catalysis. 

PMID- 25960307
TI  - Impact of KIR and HLA Genotypes on Outcomes after Reduced-Intensity Conditioning
      Hematopoietic Cell Transplantation.
AB  - Natural killer cells are regulated by killer cell immunoglobulin-like receptor
      (KIR) interactions with HLA class I ligands. Several models of natural killer
      cell reactivity have been associated with improved outcomes after myeloablative
      allogeneic hematopoietic cell transplantation (HCT), but this issue has not been
      rigorously addressed in reduced-intensity conditioning (RIC) unrelated donor
      (URD) HCT. We studied 909 patients undergoing RIC-URD HCT. Patients with acute
      myeloid leukemia (AML, n = 612) lacking >= 1 KIR ligands experienced higher grade
      III to IV acute graft-versus-host disease (GVHD) (HR, 1.6; 95% CI, 1.16 to 2.28;
      P = .005) compared to those with all ligands present. Absence of HLA-C2 for donor
      KIR2DL1 was associated with higher grade II to IV (HR, 1.4; P = .002) and III to
      IV acute GVHD (HR, 1.5; P = .01) compared with HLA-C2(+) patients. AML patients
      with KIR2DS1(+), HLA-C2 homozygous donors had greater treatment-related mortality
      compared with others (HR, 2.4; 95% CI, 1.4 to 4.2; P = .002) but did not
      experience lower relapse. There were no significant associations with outcomes
      for AML when assessing donor-activating KIRs or centromeric KIR content or for
      any donor-recipient KIR-HLA assessments in patients with myelodysplastic syndrome
      (n = 297). KIR-HLA combinations in RIC-URD HCT recapitulate some but not all KIR
      HLA effects observed in myeloablative HCT.

PMID- 25960311
TI  - Soil ecotoxicity assessment of glyphosate use under field conditions: microbial
      activity and community structure of Eubacteria and ammonia-oxidising bacteria.
AB  - BACKGROUND: A plot-scale experiment was conducted to assess the impact of field
      application rates of glyphosate on soil microbial communities by taking
      measurements of microbial activity (in terms of substrate-induced respiration and
      enzyme activity) in parallel with culture-independent approaches to assessing
      both bacterial abundance and diversity. Two rates of glyphosate, alone or in a
      mixture with 2,4-dichlorophenoxyacetic acid, were applied directly onto the soil
      surface, simulating normal use in chemical fallow in no-till systems. RESULTS: No
      consistent rate-dependent responses were observed in the microbial activity
      parameters investigated in the field plots that were exposed to glyphosate.
      Denaturant gradient gel electrophoresis (DGGE) of the overall bacterial community
      (Eubacteria) and ammonia-oxidising bacteria (AOB) revealed no effects of the high
      rate of glyphosate on the structure of the communities in comparison with the
      control. No treatment effects were observed on the abundance of Eubacteria
      shortly after treatment in 2010, while a small but significant difference between
      the high rate and the control was detected in the first sampling in 2011. The
      abundance of AOB was relatively low during the study, and treatment effects were
      undetectable. CONCLUSIONS: The absence of negative effects on soil microbial
      communities in this study suggests that glyphosate use at recommended rates poses
      low risk to the microbiota.

PMID- 25960310
TI  - RNA structure determination by solid-state NMR spectroscopy.
AB  - Knowledge of the RNA three-dimensional structure, either in isolation or as part
      of RNP complexes, is fundamental to understand the mechanism of numerous cellular
      processes. Because of its flexibility, RNA represents a challenge for
      crystallization, while the large size of cellular complexes brings solution-state
      NMR to its limits. Here, we demonstrate an alternative approach on the basis of
      solid-state NMR spectroscopy. We develop a suite of experiments and RNA labeling
      schemes and demonstrate for the first time that ssNMR can yield a RNA structure
      at high-resolution. This methodology allows structural analysis of segmentally
      labelled RNA stretches in high-molecular weight cellular machines-independent of
      their ability to crystallize-and opens the way to mechanistic studies of
      currently difficult-to-access RNA-protein assemblies.

PMID- 25960312
TI  - Influence of halogen substitutions on rates of charge tunneling across SAM-based
      large-area junctions.
AB  - This paper examines the ability of structural modifications using halogen atoms
      (F, Cl, Br, and I) to influence tunneling rates across self-assembled monolayer
      (SAM)-based junctions having the structure Ag(TS)/S(CH2)n(p-C6H4X)//Ga2O3/EGaIn,
      where S(CH2)n(p-C6H4X) is a SAM of benzenethiol (n = 0) or benzyl mercaptan (n =
      1) terminated in a hydrogen (X = H) or a halogen (X = F, Cl, Br, or I) at the
      para-position. The measured tunneling current densities (J(V); A cm(-2)) indicate
      that replacing a terminal hydrogen with a halogen atom at the X//Ga2O3 interface
      leads to a decrease in J(V) by ~*13 for S(p-C6H4X) and by ~*50 for SCH2(p-C6H4X).
      Values of J(V) for the series of halogenated SAMs were indistinguishable,
      indicating that changes in dipole moment and polarizability caused by introducing
      different halogen atoms at the interface between the SAM and the Ga2O3/EGaIn
      electrode do not significantly influence the rates of charge tunneling across the
      junctions. 

PMID- 25960313
TI  - Thermal conversion of a tailored metal-organic framework into lithium silicate
      with an unusual morphology for efficient CO2 capture.
AB  - The conversion reaction of metal-organic frameworks (MOFs) was adopted as a
      synthetic method to produce an advanced CO2 absorbent. A Li- and Si-containing
      MOF is a good precursor for lithium orthosilicate (Li4SiO4); the resulting solid
      has an unusual coral-like morphology, which provides an enhanced CO2-sorption
      performance (high uptake and fast absorption). 

PMID- 25960314
TI  - The dorsal prefrontal and dorsal anterior cingulate cortices exert complementary
      network signatures during encoding and retrieval in associative memory.
AB  - Cognitive control includes processes that facilitate execution of effortful
      cognitive tasks, including associative memory. Regions implicated in cognitive
      control during associative memory include the dorsal prefrontal (dPFC) and dorsal
      anterior cingulate cortex (dACC). Here we investigated the relative degrees of
      network-related interactions originating in the dPFC and dACC during oscillating
      phases of associative memory: encoding and cued retrieval. Volunteers completed
      an established object-location associative memory paradigm during fMRI.
      Psychophysiological interactions modeled modulatory network interactions from the
      dPFC and dACC during memory encoding and retrieval. Results were evaluated in
      second level analyses of variance with seed region and memory process as factors.
      Each seed exerted differentiable modulatory effects during encoding and
      retrieval. The dACC exhibited greater modulation (than the dPFC) on the fusiform
      and parahippocampal gyrus during encoding, while the dPFC exhibited greater
      modulation (than the dACC) on the fusiform, hippocampus, dPFC and basal ganglia.
      During retrieval, the dPFC exhibited greater modulation (than the dACC) on the
      parahippocampal gyrus, hippocampus, superior parietal lobule, and dPFC. The most
      notable finding was a seed by process interaction indicating that the dACC and
      the dPFC exerted complementary modulatory control on the hippocampus during each
      of the associative memory processes. These results provide evidence for
      differentiable, yet complementary, control-related modulation by the dACC and
      dPFC, while establishing the primacy of dPFC in exerting network control during
      both associative memory phases. Our approach and findings are relevant for
      understanding basic processes in human memory and psychiatric disorders that
      impact associative memory-related networks. 

PMID- 25960315
TI  - Single-trial classification of near-infrared spectroscopy signals arising from
      multiple cortical regions.
AB  - Near-infrared spectroscopy (NIRS) brain-computer interface (BCI) studies have
      primarily made use of measurements taken from a single cortical area. In
      particular, the anterior prefrontal cortex has been the key area used for
      detecting higher-level cognitive task performance. However, mental task execution
      typically requires coordination between several, spatially-distributed brain
      regions. We investigated the value of expanding the area of interrogation to
      include NIRS measurements from both the prefrontal and parietal cortices to
      decode mental states. Hemodynamic activity was monitored at 46 locations over the
      prefrontal and parietal cortices using a continuous-wave near-infrared
      spectrometer while 11 able-bodied adults rested or performed either the verbal
      fluency task (VFT) or Stroop task. Offline classification was performed for the
      three possible binary problems using 25 iterations of bagging with a linear
      discriminant base classifier. Classifiers were trained on a 10 dimensional
      feature set. When all 46 measurement locations were considered for
      classification, average accuracies of 80.4+/-7.0%, 82.4+/-7.6%, and 82.8+/-5.9%
      in differentiating VFT vs rest, Stroop vs rest and VFT vs Stroop, respectively,
      were obtained. Relative to using measurements from the anterior PFC alone, an
      overall average improvement of 11.3% was achieved. Utilizing NIRS measurements
      from the prefrontal and parietal cortices can be of value in classifying mental
      states involving working memory and attention. NIRS-BCI accuracies may be
      improved by incorporating measurements from several, distinct cortical regions,
      rather than a single area alone. Further development of an NIRS-BCI supporting
      combinations of VFT, Stroop task and rest states is also warranted. 

PMID- 25960316
TI  - A signal processing application for evaluating self-monitoring blood glucose
      strategies in a software agent model.
AB  - We propose the signal processing technique of calculating a cross-correlation
      function and an average deviation between the continuous blood glucose and the
      interpolation of limited blood glucose samples to evaluate blood glucose
      monitoring frequency in a self-aware patient software agent model. The diabetic
      patient software agent model [1] is a 24-h circadian, self-aware, stochastic
      model of a diabetic patient's blood glucose levels in a software agent
      environment. The purpose of this work is to apply a signal processing technique
      to assist patients and physicians in understanding the extent of a patient's
      illness using a limited number of blood glucose samples. A second purpose of this
      work is to determine an appropriate blood glucose monitoring frequency in order
      to have a minimum number of samples taken that still provide a good understanding
      of the patient's blood glucose levels. For society in general, the monitoring
      cost of diabetes is an extremely important issue, and these costs can vary
      tremendously depending on monitoring approaches and monitoring frequencies. Due
      to the cost and discomfort associated with blood glucose monitoring, today,
      patients expect monitoring frequencies specific to their health profile. The
      proposed method quantitatively assesses various monitoring protocols (from 6
      times per day to 1 time per week) in nine predefined categories of patient agents
      in terms of risk factors of health status and age. Simulation results show that
      sampling 6 times per day is excessive, and not necessary for understanding the
      dynamics of the continuous signal in the experiments. In addition, patient agents
      in certain conditions only need to sample their blood glucose 1 time per week to
      have a good understanding of the characteristics of their blood glucose. Finally,
      an evaluation scenario is developed to visualize this concept, in which
      appropriate monitoring frequencies are shown based on the particular conditions
      of patient agents. This base line can assist people in determining an appropriate
      monitoring frequency based on their personal health profile. 

PMID- 25960317
TI  - Lentivirus mediated over expression of CGRP inhibited oxidative stress in Schwann
      cell line.
AB  - CGRP is reported to be implicated in the process of diabetes and neuronal
      disease. However, the role and underlying mechanism of CGRP involved in diabetic
      neuropathy is unknown. Schwann cells play a central role in diabetic neuropathy,
      therefore the protective effect of CGRP on Schwann cells exposed to high glucose
      is determined. In the present study, full-length CGRP cDNA was isolated and then
      transferred to gateway adapted lentivirus expression vector by LR recombination
      reaction. Afterwards, the CGRP bearing recombinant virus was prepared in 293 FT
      cells and used to infect Schwann cells. The viability and superoxide anions of
      Schwann cells were evaluated following stimulation with high glucose, and levels
      of SOD, MDA and NOX1 were assessed. The results suggested that CGRP expression
      was up-regulated following lentivirus transfection. Lenti-CGRP increased cell
      viability in high glucose, but the effect was transient. Further lenti-CGRP
      protected against oxidative stress in Schwann cells triggered by high glucose and
      lenti-CGRP was effective in increasing SOD and decreasing MDA level. Meanwhile,
      the increased level of NOX1 caused by high glucose was reversed by lenti-CGRP
      overexpression. We therefore, suggest that lenti-CGRP may play a role in
      inhibiting oxidative stress in Schwann cell lines following hyperglycemic
      stimulation.

PMID- 25960319
TI  - Tailoring Ru(II) pyridine/triazole oxygenation catalysts and using
      photoreactivity to probe their electronic properties.
AB  - Tuning of ligand properties is at the heart of influencing chemical reactivity
      and generating tailor-made catalysts. Herein, three series of complexes
      [Ru(L)(Cl)(X)]PF6 (X=DMSO, PPh3 , or CD3 CN) with tripodal ligands (L1-L5)
      containing pyridine and triazole arms are presented. Triazole-for-pyridine
      substitution and the substituent at the triazole systematically influence the
      redox behavior and photoreactivity of the complexes. The mechanism of the light
      driven ligand exchange of the DMSO complexes in CD3 CN could be elucidated, and
      two seven-coordinate intermediates were identified. Finally, tuning of the ligand
      framework was applied to the catalytic oxygenation of alkanes, for which the DMSO
      complexes were the best catalysts and the yield improved with increasing number
      of triazole arms. These results thus show how click-derived ligands can be tuned
      on demand for catalytic processes. 

PMID- 25960318
TI  - Celecoxib influences steroid sulfonation catalyzed by human recombinant
      sulfotransferase 2A1.
AB  - Celecoxib has been reported to switch the human SULT2A1-catalyzed sulfonation of
      17beta-estradiol (17beta-E2) from the 3- to the 17-position. The effects of
      celecoxib on the sulfonation of selected steroids catalyzed by human SULT2A1 were
      assessed through in vitro and in silico studies. Celecoxib inhibited SULT2A1
      catalyzed sulfonation of dehydroepiandrosterone (DHEA), androst-5-ene-3beta,
      17beta-diol (AD), testosterone (T) and epitestosterone (Epi-T) in a concentration
      dependent manner. Low MUM concentrations of celecoxib strikingly enhanced the
      formation of the 17-sulfates of 6-dehydroestradiol (6D-E2), 17beta
      dihydroequilenin (17beta-Eqn), 17beta-dihydroequilin (17beta-Eq), and 9
      dehydroestradiol (9D-E2) as well as the overall rate of sulfonation. For 6D-E2,
      9D-E2 and 17beta-Eqn, celecoxib inhibited 3-sulfonation, however 3-sulfonation of
      17beta-Eq was stimulated at celecoxib concentrations below 40 MUM. Ligand docking
      studies in silico suggest that celecoxib binds in the substrate-binding site of
      SULT2A1 in a manner that prohibits the usual binding of substrates but
      facilitates, for appropriately shaped substrates, a binding mode that favors 17
      sulfonation.

PMID- 25960321
TI  - Magnetic Resonance Imaging-guided Radiation Therapy: Technological Innovation
      Provides a New Vision of Radiation Oncology Practice.

PMID- 25960320
TI  - Reproducibility of quantitative susceptibility mapping in the brain at two field
      strengths from two vendors.
AB  - PURPOSE: To assess the reproducibility of brain quantitative susceptibility
      mapping (QSM) in healthy subjects and in patients with multiple sclerosis (MS) on
      1.5 and 3T scanners from two vendors. MATERIALS AND METHODS: Ten healthy
      volunteers and 10 patients were scanned twice on a 3T scanner from one vendor.
      The healthy volunteers were also scanned on a 1.5T scanner from the same vendor
      and on a 3T scanner from a second vendor. Similar imaging parameters were used
      for all scans. QSM images were reconstructed using a recently developed nonlinear
      morphology-enabled dipole inversion (MEDI) algorithm with L1 regularization.
      Region-of-interest (ROI) measurements were obtained for 20 major brain
      structures. Reproducibility was evaluated with voxel-wise and ROI-based Bland
      Altman plots and linear correlation analysis. RESULTS: ROI-based QSM measurements
      showed excellent correlation between all repeated scans (correlation coefficient
      R >= 0.97), with a mean difference of less than 1.24 ppb (healthy subjects) and
      4.15 ppb (patients), and 95% limits of agreements of within -25.5 to 25.0 ppb
      (healthy subjects) and -35.8 to 27.6 ppb (patients). Voxel-based QSM measurements
      had a good correlation (0.64 <= R <= 0.88) and limits of agreements of -60 to 60
      ppb or less. CONCLUSION: Brain QSM measurements have good interscanner and same
      scanner reproducibility for healthy and MS subjects, respectively, on the systems
      evaluated in this study.

PMID- 25960322
TI  - Addressing phototoxicity observed in a novel series of biaryl derivatives:
      discovery of potent, selective and orally active phosphodiesterase 10A inhibitor
      ASP9436.
AB  - We synthesized several biaryl derivatives as PDE10A inhibitors to prevent
      phototoxicity of 2-[4-({[1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3
      yl]oxy}methyl)phenyl]quinoline (1) and found that the energy difference between
      the energy-minimized conformation and the coplanar conformation of the biaryl
      moiety helped facilitate prediction of the phototoxic potential of biaryl
      compounds. Replacement of the quinoline ring of 1 with N-methyl benzimidazole
      increased this energy difference and prevented phototoxicity in the 3T3 NRU test.
      Further optimization identified 1-methyl-5-(1-methyl-3-{[4-(1-methyl-1H
      benzimidazol-4-yl)phenoxy]methyl}-1H-pyrazol-4-yl)pyridin-2(1H)-one (38b).
      Compound 38b exhibited good selectivity against other PDEs, and oral
      administration of 38b improved visual-recognition memory deficit in mice at doses
      of 0.001 and 0.003mg/kg in the novel object recognition test. ASP9436
      (sesquiphosphate of 38b) may therefore be used for the treatment of schizophrenia
      with a low risk of phototoxicity.

PMID- 25960323
TI  - Phospholipid derivatives of cladribine and fludarabine: synthesis and biological
      properties.
AB  - Phospholipid derivatives of anticancer nucleosides cladribine and fludarabine (F
      ara-A) bearing 1,2- and 1,3-diacylglycerol moieties have been prepared by the H
      phosphonate approach using 1,1,3,3-tetraisopropyldisiloxane-1,3-diyl protecting
      group for cladribine and a combination of tert-butyldimethylsilyl and levulinyl
      protecting groups for 2-fluoroadenine nucleosides. The synthesized conjugates
      exhibited lower in vitro antiproliferative activity against human tumor cell
      lines in comparison with the same concentrations of the parent cladribine and
      fludarabine phosphate. In the course of biokinetic study, it was found that
      intragastric administration of phospholipid F-ara-A derivatives to Wistar rats
      and ICR outbred male mice led to a slow release of F-ara-A into the bloodstream,
      a smooth increase in nucleoside concentration, and prolonged serum circulation of
      liberated nucleoside. The oral bioavailability of F-ara-A from 1,2
      dimyristoylglycerophosphate derivative 29 was similar to its oral bioavailability
      from fludarabine phosphate.

PMID- 25960324
TI  - Effect of intercalator substituent and nucleotide sequence on the stability of
      DNA- and RNA-naphthalimide complexes.
AB  - DNA intercalators are commonly used as anti-cancer and anti-tumor agents. As a
      result, it is imperative to understand how changes in intercalator structure
      affect binding affinity to DNA. Amonafide and mitonafide, two naphthalimide
      derivatives that are active against HeLa and KB cells in vitro, were previously
      shown to intercalate into DNA. Here, a systematic study was undertaken to change
      the 3-substituent on the aromatic intercalator 1,8-naphthalimide to determine how
      11 different functional groups with a variety of physical and electronic
      properties affect binding of the naphthalimide to DNA and RNA duplexes of
      different sequence compositions and lengths. Wavelength scans, NMR titrations,
      and circular dichroism were used to investigate the binding mode of 1,8
      naphthalimide derivatives to short synthetic DNA. Optical melting experiments
      were used to measure the change in melting temperature of the DNA and RNA
      duplexes due to intercalation, which ranged from 0 to 19.4 degrees C. Thermal
      stabilities were affected by changing the substituent, and several patterns and
      idiosyncrasies were identified. By systematically varying the 3-substituent, the
      binding strength of the same derivative to various DNA and RNA duplexes was
      compared. The binding strength of different derivatives to the same DNA and RNA
      sequences was also compared. The results of these comparisons shed light on the
      complexities of site specificity and binding strength in DNA-intercalator
      complexes. For example, the consequences of adding a 5'-TpG-3' or 5'-GpT-3' step
      to a duplex is dependent on the sequence composition of the duplex. When added to
      a poly-AT duplex, naphthalimide binding was enhanced by 5.6-11.5 degrees C, but
      when added to a poly-GC duplex, naphthalimide binding was diminished by 3.2-6.9
      degrees C.

PMID- 25960326
TI  - Macrocyclic analogues of the diuretic insect neuropeptide helicokinin I show
      strong receptor-binding.
AB  - Helicokinin I, a diuretic neuropeptide of the relevant cotton pest Helicoverpa
      zea represents a promising target for the design of insect neuropeptide mimetics.
      Using a ring-closing metathesis reaction, N-terminal bridged macrocyclic
      helicokinin I analogues with different rigidity were prepared and tested in a
      helicokinin receptor assay. A partially peptidomimetic helicokinin analogue,
      containing two structural modifications provides a deeper insight into the
      structural-requirements for receptor-binding.

PMID- 25960325
TI  - Efficient method for iodine radioisotope labeling of cyclooctyne-containing
      molecules using strain-promoted copper-free click reaction.
AB  - Herein we report an efficient method for iodine radioisotope labeling of
      cyclooctyne-containing molecules using copper-free click reaction. For this
      study, radioiodination using the tin precursor 2 was carried out at room
      temperature to give (125)I-labeled azide ([(125)I]1) with high radiochemical
      yield (85%) and excellent radiochemical purity. Dibenzocyclooctyne (DBCO)
      containing cRGD peptide and gold nanoparticle were labeled with [(125)I]1 at 37
      degrees C for 30min to give triazoles with good radiochemical yields (67-95%). We
      next carried out tissue biodistribution study of [(125)I]1 in normal ICR mice to
      investigate the level of organ accumulation which needs to be considered for pre
      targeted in vivo imaging. Large amount of [(125)I]1 distributed rapidly in liver
      and kidney from bloodstream and underwent rapid renal and hepatobiliary
      clearance. Moreover [(125)I]1 was found to be highly stable (>92%) in mouse serum
      for 24h. Therefore [(125)I]1 could be used as a potentially useful radiotracer
      for pre-targeted imaging. Those results clearly indicated that the present
      radiolabeling method using copper free click reaction would be quite useful for
      both in vitro and in vivo labeling of DBCO group containing molecules with iodine
      radioisotopes.

PMID- 25960328
TI  - Importance of substantial weight loss for altering gene expression during
      cardiovascular lifestyle modification.
AB  - OBJECTIVE: To examine relationships between weight loss through changes in
      lifestyle and peripheral blood gene expression profiles. METHODS: A prospective
      nonrandomized trial was conducted over 1 year in participants undergoing
      intensive lifestyle modification to reverse or stabilize progression of coronary
      artery disease. Cardiovascular risk factors, inflammatory biomarkers, and gene
      expression as a function of weight loss were assessed in 89 lifestyle
      participants and 71 retrospectively matched controls undergoing usual care.
      RESULTS: Substantial weight loss (-15.2 +/- 3.8%) in lifestyle participants (n =
      33) was associated with improvement in selected cardiovascular risk factors and
      significant changes in peripheral blood gene expression from pre- to post
      intervention: 132 unique genes showed significant expression changes (false
      discovery rate corrected P-value <0.05 and fold-change >=1.4). Altered molecular
      pathways were related to immune function and inflammatory responses involving
      endothelial activation. In contrast, participants losing minimal weight (-3.1 +/-
      2.5%, n = 32) showed only minor changes in cardiovascular risk factors and
      markers of inflammation and no changes in gene expression compared to non
      intervention controls after 1 year. CONCLUSIONS: Weight loss (>=10%) during
      lifestyle modification is associated with down-regulation of genetic pathways
      governing interactions between circulating immune cells and the vascular
      endothelium and may be required to successfully reduce CVD risk.

PMID- 25960327
TI  - Variation in koala microbiomes within and between individuals: effect of body
      region and captivity status.
AB  - Metagenomic analysis of 16S ribosomal RNA has been used to profile microbial
      communities at high resolution, and to examine their association with host diet
      or diseases. We examined the oral and gut microbiome composition of two captive
      koalas to determine whether bacterial communities are unusual in this species,
      given that their diet consists almost exclusively of Eucalyptus leaves. Despite a
      highly specialized diet, koala oral and gut microbiomes were similar in
      composition to the microbiomes from the same body regions of other mammals.
      Rectal swabs contained all of the diversity present in faecal samples, along with
      additional taxa, suggesting that faecal bacterial communities may merely
      subsample the gut bacterial diversity. Furthermore, the faecal microbiomes of the
      captive koalas were similar to those reported for wild koalas, suggesting that
      captivity may not compromise koala microbial health. Since koalas frequently
      suffer from ocular diseases caused by Chlamydia infection, we also examined the
      eye microbiome composition of two captive koalas, establishing the healthy
      baseline for this body part. The eye microbial community was very diverse,
      similar to other mammalian ocular microbiomes but with an unusually high
      representation of bacteria from the family Phyllobacteriaceae. 

PMID- 25960329
TI  - Low-density lipoprotein peptide-combined DNA nanocomplex as an efficient
      anticancer drug delivery vehicle.
AB  - DNA is a type of potential biomaterials for drug delivery due to its nanoscale
      geometry, loading capacity of therapeutics, biocompatibility, and
      biodegradability. Unfortunately, DNA is easily degraded by DNases in the body
      circulation and has low intracellular uptake. In the present study, we selected
      three cationic polymers polyethylenimine (PEI), hexadecyl trimethyl ammonium
      bromide (CTAB), and low-density lipoprotein (LDL) receptor targeted peptide
      (RLT), to modify DNA and improve the issues. A potent anti-tumor anthracycline
      doxorubicin (DOX) was intercalated into DNA non-covalently and the DOX/DNA was
      then combined with PEI, CTAB, and RLT, respectively. Compact nanocomplexes were
      formed by electrostatic interaction and could potentially protect DNA from
      DNases. More importantly, RLT had the potential to enhance intracellular uptake
      by LDL receptor mediated endocytosis. In a series of in vitro experiments, RLT
      complexed DNA enhanced intracellular delivery of DOX, increased tumor cell death
      and intracellular ROS production, and reduced intracellular elimination of DOX.
      All results suggested that the easily prepared and targeted RLT/DNA nanocomplexes
      had great potential to be developed into a formulation for doxorubicin with
      enhanced anti-tumor activity. 

PMID- 25960330
TI  - Effect of different intestinal conditions on the intermolecular interaction
      between insulin and cell-penetrating peptide penetratin and on its contribution
      to stimulation of permeation through intestinal epithelium.
AB  - Our recent studies have shown that the coadministration of cell-penetrating
      peptides (CPPs) is a potential strategy for oral delivery of peptide- and protein
      based biopharmaceuticals. The intermolecular interaction between drug and CPP is
      an essential factor in the effective delivery of these drugs, but the
      characteristics of the interaction under the conditions of the intestinal lumen
      remain unknown. In this study, therefore, we examined the characteristics of
      binding of the amphipathic CPP penetratin to insulin and the efficiency of its
      enhancement of epithelial insulin transport at different pH and in simulated
      intestinal fluids (SIFs). The binding between insulin and penetratin was pH
      dependent and particularly decreased at pH 5.0. In addition, we clarified that
      the sodium taurocholate (NaTC) present in two types of SIF (fasted-state SIF
      [FaSSIF] and fed-state SIF [FeSSIF]) affected binding efficiency. However, the
      permeation of insulin through a Caco-2 cell monolayer was significantly
      facilitated by coincubation with l- or d-penetratin at various pH values.
      Moreover, the permeation-stimulating effect of l-penetratin was observed in
      FaSSIF containing NaTC and lecithin, but not in 3mM NaTC solution, suggesting
      that the presence of lecithin was the key factor in maintaining the ability of
      penetratin to enhance the intestinal absorption of biopharmaceuticals. This
      report describes the essential considerations for in vivo use and clinical
      application of a CPP-based oral delivery strategy. 

PMID- 25960331
TI  - New prostaglandin analog formulation for glaucoma treatment containing
      cyclodextrins for improved stability, solubility and ocular tolerance.
AB  - Latanoprost is a practically insoluble prostaglandin F2alpha analog considered a
      first-line agent for glaucoma treatment. From a pharmaceutical point of view,
      latanoprost is challenging to be formulated as an eye drop due to its poor water
      solubility and the presence of an ester bond that needs to be cleaved in vivo but
      maintained unchanged during storage. Cyclodextrins (CDs) are known to form
      complexes with hydrophobic drugs, influencing their stability, availability,
      solubility, and tolerance in a non-predictable manner. A variety of CDs including
      native alpha, beta, and gammaCDs as well as substituted hydroxypropylbetaCD,
      hydroxypropylgammaCD, dimethylbetaCD, sulphatedbetaCD, and propylaminobetaCD were
      screened and the most appropriate CD for the formulation of latanoprost for an
      ocular topical application was selected. Among the tested CDs, propylaminobetaCD
      had the best trade-off between latanoprost stability and availability, which was
      confirmed by its complex constant value of 3129M(-1). Phase-solubility and NMR
      investigations demonstrated that the propylaminobetaCD effectively formed a
      complex involving the ester group of latanoprost providing protection to its
      ester bond, while ensuring proper latanoprost solubilization. Furthermore, in
      vivo experiments demonstrated that the latanoprost-propylaminobetaCD formulation
      led to lower ocular irritation than the commercial latanoprost formulation used
      as a reference. The latanoprost-propylaminobetaCD formulation was demonstrated to
      successfully address the main stability, solubility, and tolerance limitations of
      topical ocular latanoprost therapy for glaucoma. 

PMID- 25960332
TI  - A pragmatic approach for engineering porous mannitol and mechanistic evaluation
      of particle performance.
AB  - The importance of mannitol has increased recently as an emerging diluent for
      orodispersible dosage forms. The study aims to prepare spray dried mannitol
      retaining high porosity and mechanical strength for the development of orally
      disintegrating tablets (ODTs). Aqueous feed of d-mannitol (10% w/v) comprising
      ammonium bicarbonate, NH4HCO3 (5% w/v) as pore former was spray dried at inlet
      temperature of 110-170 degrees C. Compacts were prepared at 151MPa and
      characterized for porosity, hardness and disintegration time. Particle morphology
      and drying mechanisms were studied using thermal (HSM, DSC and TGA) and
      polymorphic (XRD) methods. Tablet porosity increased from 0.20+/-0.002 for pure
      mannitol to 0.53+/-0.03 using fabricated porous mannitol. Disintegration time
      dropped by 50-77% from 135+/-5.29s for pure mannitol to 75.33+/-2.52-31.67+/
      1.53s for mannitol 110-170 degrees C. Hardness increased by 150% at 110 degrees C
      (258.67+/-28.89N) and 30% at 150 degrees C (152.70+/-10.58N) compared to pure
      mannitol tablets (104.17+/-1.70N). Increasing inlet temperature resulted in
      reducing tablet hardness due to generation of 'micro-sponge'-like particles
      exhibiting significant elastic recovery. Impact of mannitol polymorphism on
      plasticity/elasticity cannot be ruled out as a mixture of alpha and beta
      polymorphs formed upon spray drying. 

PMID- 25960333
TI  - Genetic diversity and host associations in Campylobacter jejuni from human cases
      and broilers in 2000 and 2008.
AB  - Campylobacter jejuni is an important food-borne pathogen, with a global
      distribution. It can colonize numerous host species, including both domestic and
      wild animals, but is particularly associated with birds (poultry and wild birds).
      For human campylobacteriosis, poultry products are deemed the most significant
      risk factor for acquiring infection. We conducted a genotyping and host
      attribution study of a large representative collection of C. jejuni isolated from
      humans and broilers in Sweden in the years 2000 and 2008. In total 673 broiler
      and human isolates from 10 different abattoirs and 6 different hospitals were
      genotyped with multilocus sequence typing. Source attribution analyses confirmed
      the strong linkage between broiler C. jejuni and domestic human cases, but also
      indicated a significant association to genotypes more commonly found in wild
      birds. Genotype distributions did not change dramatically between the two study
      years, suggesting a stable population of infecting bacteria. 

PMID- 25960334
TI  - Mechanisms of antimicrobial resistant Salmonella enterica transmission associated
      with starling-livestock interactions.
AB  - Bird-livestock interactions have been implicated as potential sources for
      bacteria within concentrated animal feeding operations (CAFO). European starlings
      (Sturnus vulgaris) in particular are known to contaminate cattle feed and water
      with Salmonella enterica through their fecal waste. We propose that fecal waste
      is not the only mechanisms through which starlings introduce S. enterica to CAFO.
      The goal of this study was to assess if starlings can mechanically move S.
      enterica. We define mechanical movement as the transportation of media containing
      S. enterica, on the exterior of starlings within CAFO. We collected 100 starlings
      and obtained external wash and gastrointestinal tract (GI) samples. We also
      collected 100 samples from animal pens. Within each pen we collected one cattle
      fecal, feed, and water trough sample. Isolates from all S. enterica positive
      samples were subjected to antimicrobial susceptibility testing. All sample types,
      including 17% of external starling wash samples, contained S. enterica. All
      sample types had at least one antimicrobial resistant (AMR) isolate and starling
      GI samples harbored multidrug resistant S. enterica. The serotypes isolated from
      the starling external wash samples were all found in the farm environment and
      11.8% (2/17) of isolates from positive starling external wash samples were
      resistant to at least one class of antibiotics. This study provides evidence of a
      potential mechanism of wildlife introduced microbial contamination in CAFO.
      Mechanical movement of microbiological hazards, by starlings, should be
      considered a potential source of bacteria that is of concern to veterinary,
      environmental and public health. 

PMID- 25960335
TI  - Identification of three antigen epitopes on the nucleocapsid protein of the
      genotype C of bovine parainfluenza virus type 3.
AB  - Bovine parainfluenza virus type 3 (BPIV3) is an important respiratory tract
      pathogen for both young and adult cattle. So far, three genotypes A, B and C of
      BPIV3 have been described on the basis of genetic and phylogenetic analysis. But
      fine mapping of epitopes of BPIV3 is scant and the antigenic variations among the
      three genotypes of BPIV3 have not been reported. Nucleocapsid protein (NP) is the
      most abundant protein in the virion and highly conserved in BPIV3, which is
      crucial for the induction of protective immunity in host. To identify antigenic
      determinants of BPIV3 NP, a panel of monoclonal antibodies (mAbs) was tested
      against a series of overlapping recombinant NP fragments expressed in Escherichia
      coli. Firstly, six monoclonal antibodies (mAbs) against NP of the genotype C of
      BPIV3 (BPIV3c) were generated by using the purified BPIV3c strain SD0835 as
      immunogen and the recombinant NP of SD0835 as screening antigen. Then three
      antigen epitopes were identified with the six mAbs. One epitope
      (91)GNNADVKYVIYM(102) was recognized by mAb 5E5. The mAbs 7G5, 7G8, 7G9, and 7H5
      were reactive with another epitope (407)FYKPTGG(413). The third epitope
      (428)ESRGDQDQ(435) was reactive with mAb 6F8. Further analysis showed that the
      epitope (91-102 amino acids [aa]) was the most conserved and reactive with mAb
      5E5 for all three genotypes of BPIV3 and HPIV3. The epitope (407-413 aa) was
      relatively conserved and reactive with mAbs 7G5, 7G8, 7G9, and 7H5 for BPIV3a,
      BPIV3c and HPIV3, but not reactive with BPIV3b. The epitope (428-435 aa) was less
      conserved and was reactive only with mAb 6F8 for BPIV3a and BPIV3c. These results
      suggested that there were evident antigenic variations among the three genotypes
      of BPIV3 and HPIV3. The mAb 6F8 could be used to detect BPIV3a and BPIV3c. The
      mAbs 7G5, 7G8, 7G9, and 7H5 might be used for differentiate BPIV3a, BPIV3c and
      HPIV3 from BPIV3b. The mAb 5E5 might be used for detecting all three types of
      BPIV3 and HPIV3. The results in this study would have potential applications in
      the development of suitable diagnostic techniques for BPIV3, which was prevalent
      in China. 

PMID- 25960336
TI  - Adaptive sampling rate control for networked systems based on statistical
      characteristics of packet disordering.
AB  - This paper investigates an adaptive sampling rate control scheme for networked
      control systems (NCSs) subject to packet disordering. The main objectives of the
      proposed scheme are (a) to avoid heavy packet disordering existing in
      communication networks and (b) to stabilize NCSs with packet disordering,
      transmission delay and packet loss. First, a novel sampling rate control
      algorithm based on statistical characteristics of disordering entropy is
      proposed; secondly, an augmented closed-loop NCS that consists of a plant, a
      sampler and a state-feedback controller is transformed into an uncertain and
      stochastic system, which facilitates the controller design. Then, a sufficient
      condition for stochastic stability in terms of Linear Matrix Inequalities (LMIs)
      is given. Moreover, an adaptive tracking controller is designed such that the
      sampling period tracks a desired sampling period, which represents a significant
      contribution. Finally, experimental results are given to illustrate the
      effectiveness and advantages of the proposed scheme. 

PMID- 25960337
TI  - An iterative approach to respiratory self-navigated whole-heart coronary MRA
      significantly improves image quality in a preliminary patient study.
AB  - PURPOSE: In respiratory self-navigated coronary MRA, the selection of a reference
      position may have a direct effect on image quality. While end-expiration is
      commonly used as reference, it may be ill defined in cases of irregular
      breathing. Here, an iterative self-navigation approach that operates without a
      reference position was implemented and tested in healthy volunteers and patients.
      METHODS: Data were acquired in 15 healthy volunteers and in 23 patients. Images
      obtained with end-expiratory self-navigation were compared with those obtained
      with the iterative approach that incorporates cross-correlation to iteratively
      minimize a global measure of respiratory displacement. Vessel sharpness, length,
      signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were evaluated
      while differences in breathing patterns between the two sub-groups were assessed,
      too. RESULTS: Vessel sharpness and length were similar for both methods in
      healthy volunteers. In patients, a significant improvement in vessel sharpness
      and length was obtained using the iterative approach. SNR and CNR remained
      constant. While end-expiration was the most frequent respiratory phase in healthy
      volunteers (57.6 +/- 16.2%), intermediate respiratory phases (43.4 +/- 30.1%)
      were predominantly found in patients. CONCLUSION: An iterative approach to
      respiratory motion correction in self-navigation may lead to significant
      improvements in coronary MRA image quality in patients with a less consistent end
      expiratory respiratory phase.

PMID- 25960338
TI  - High-titer production and strong antimicrobial activity of sophorolipids from
      Rhodotorula bogoriensis.
AB  - Rhodotorula bogoriensis produces sophorolipids (SLs) that contain 13
      hydroxydocosanoic acid (OH-C22 ) as the lipid moiety. A systematic study was
      conducted to further understand the fermentative production of SLs containing OH
      C22 (C22 -SL) by R. bogoriensis. Shake-flask studies showed that R. bogoriensis
      consumed glucose at a slow pace. HPLC analysis of the C22 -SL products from shake
      flask fermentations at different glucose concentrations showed a correlation
      between glucose depletion and the extent of C22 -SL deacetylation. A large-scale
      bioreactor fermentation resulted in the isolation of C22 -SL at a volumetric
      product yield of 51 g/L. HPLC analysis of C22 -SL product from the bioreactor
      fermentation corroborated the finding that glucose depletion correlated with
      extensive deacetylation of C22 -SL. The antimicrobial activity of C22 -SL was
      established for the first time to be stronger than the C18 -SL from Candida
      bombicola against Propionibacterium acnes in a plate assay.

PMID- 25960339
TI  - Critical role of a pre-purge setup in the thermal desorption analysis of volatile
      organic compounds by gas chromatography with mass spectrometry.
AB  - In general, volatile organic compounds in ambient air are quantified by following
      a well-defined standard calibration procedure using a gas-/liquid-phase standard.
      If the liquid standard is analyzed by a thermal desorption, the solvent effect is
      unavoidable through the alteration of breakthrough properties or retention times.
      To learn more about the variables of the thermal desorption-based analysis, the
      effect of pre-purge conditions was evaluated for 18 volatile organic compounds
      with different types of sorbent tube materials by fixing standard volume (1 MUL)
      and flow rate (100 mL/min). The gas phase calibration was also carried out as
      reference for the non-solvent effect. A single tube filled with Tenax TA
      exhibited the least solvent effect with the short pre-purge (1 min), while being
      subject to the breakthrough at or above 10 min pre-purge. For a three-bed sorbent
      tube with Carboxen 1000, at least 10 min of pre-purge was needed for the
      compounds with a retention time close to methanol (e.g., propanal). Another three
      bed tube with Carbopack X reduced the solvent effect efficiently for a short pre
      purge (2 min) without the breakthrough. As such, the solvent effect can be
      adjusted by the proper control of the sorbent tube application. 

PMID- 25960340
TI  - RNA-directed repair of DNA double-strand breaks.
AB  - DNA double-strand breaks (DSBs) are among the most deleterious DNA lesions, which
      if unrepaired or repaired incorrectly can cause cell death or genome instability
      that may lead to cancer. To counteract these adverse consequences, eukaryotes
      have evolved a highly orchestrated mechanism to repair DSBs, namely DNA-damage
      response (DDR). DDR, as defined specifically in relation to DSBs, consists of
      multi-layered regulatory modes including DNA damage sensors, transducers and
      effectors, through which DSBs are sensed and then repaired via DNAprotein
      interactions. Unexpectedly, recent studies have revealed a direct role of RNA in
      the repair of DSBs, including DSB-induced small RNA (diRNA)-directed and RNA
      templated DNA repair. Here, we summarize the recent discoveries of RNA-mediated
      regulation of DSB repair and discuss the potential impact of these novel RNA
      components of the DSB repair pathway on genomic stability and plasticity. 

PMID- 25960342
TI  - Skin lesion tracking using structured graphical models.
AB  - An automatic pigmented skin lesions tracking system, which is important for early
      skin cancer detection, is proposed in this work. The input to the system is a
      pair of skin back images of the same subject captured at different times. The
      output is the correspondence (matching) between the detected lesions and the
      identification of newly appearing and disappearing ones. First, a set of
      anatomical landmarks are detected using a pictorial structure algorithm. The
      lesions that are located within the polygon defined by the landmarks are
      identified and their anatomical spatial contexts are encoded by the landmarks.
      Then, these lesions are matched by labeling an association graph using a tensor
      based algorithm. A structured support vector machine is employed to learn all
      free parameters in the aforementioned steps. An adaptive learning approach (on
      the-fly vs offline learning) is applied to set the parameters of the matching
      objective function using the estimated error of the detected landmarks. The
      effectiveness of the different steps in our framework is validated on 194 skin
      back images (97 pairs). 

PMID- 25960343
TI  - Four decades of transmission of a multidrug-resistant Mycobacterium tuberculosis
      outbreak strain.
AB  - The rise of drug-resistant strains is a major challenge to containing the
      tuberculosis (TB) pandemic. Yet, little is known about the extent of resistance
      in early years of chemotherapy and when transmission of resistant strains on a
      larger scale became a major public health issue. Here we reconstruct the timeline
      of the acquisition of antimicrobial resistance during a major ongoing outbreak of
      multidrug-resistant TB in Argentina. We estimate that the progenitor of the
      outbreak strain acquired resistance to isoniazid, streptomycin and rifampicin by
      around 1973, indicating continuous circulation of a multidrug-resistant TB strain
      for four decades. By around 1979 the strain had acquired additional resistance to
      three more drugs. Our results indicate that Mycobacterium tuberculosis (Mtb) with
      extensive resistance profiles circulated 15 years before the outbreak was
      detected, and about one decade before the earliest documented transmission of Mtb
      strains with such extensive resistance profiles globally. 

PMID- 25960345
TI  - Similar L-dopa-stimulated motor activity in mice with adult-onset 6
      hydroxydopamine-induced symmetric dopamine denervation and in transcription
      factor Pitx3 null mice with perinatal-onset symmetric dopamine denervation.
AB  - The transcription factor Pitx3 null mutant (Pitx3Null) mice have a constitutive
      perinatal-onset and symmetric bilateral dopamine (DA) loss in the striatum. In
      these mice l-3,4-dihydroxyphenylalanine (l-dopa) induces apparently normal
      horizontal movements (walking) but also upward movements consisting of the
      vertical body trunk and waving paws that are absent in normal animals and in
      animals with the classic unilateral 6-hydroxydopamine (6-OHDA) lesion-induced DA
      denervation. Thus, a concern is that the perinatal timing of the DA loss and
      potential developmental abnormalities in Pitx3Null mice may underlie these upward
      movements, thus reducing the usefulness as a DA denervation model. Here we show
      that in normal wild-type (Pitx3WT) mice with adult-onset symmetric, bilateral 6
      OHDA-induced DA lesion in the dorsal striatum, l-dopa induces normal horizontal
      movements and upward movements that are qualitatively identical to those in
      Pitx3Null mice. Furthermore, after unilateral 6-OHDA lesion of the residual DA
      innervation in the striatum in Pitx3Null mice, l-dopa induces contraversive
      rotation that is similar to that in Pitx3WT mice with the classic unilateral 6
      OHDA lesion. These results indicate that in Pitx3Null mice, the bilateral
      symmetric DA denervation in the dorsal striatum is sufficient for expressing the
      l-dopa-induced motor phenotype and the perinatal timing of their DA loss is not a
      determining factor, providing further evidence that Pitx3Null mice are a
      convenient and suitable mouse model to study the consequences of DA loss and
      dopaminergic replacement therapy in Parkinson's disease. 

PMID- 25960344
TI  - Cochlear nucleus whole mount explants promote the differentiation of neuronal
      stem cells from the cochlear nucleus in co-culture experiments.
AB  - The cochlear nucleus is the first brainstem nucleus to receive sensory input from
      the cochlea. Depriving this nucleus of auditory input leads to cellular and
      molecular disorganization which may potentially be counteracted by the activation
      or application of stem cells. Neuronal stem cells (NSCs) have recently been
      identified in the neonatal cochlear nucleus and a persistent neurogenic niche was
      demonstrated in this brainstem nucleus until adulthood. The present work
      investigates whether the neurogenic environment of the cochlear nucleus can
      promote the survival of engrafted NSCs and whether cochlear nucleus-derived NSCs
      can differentiate into neurons and glia in brain tissue. Therefore, cochlear
      nucleus whole-mount explants were co-cultured with NSCs extracted from either the
      cochlear nucleus or the hippocampus and compared to a second environment using
      whole-mount explants from the hippocampus. Factors that are known to induce
      neuronal differentiation were also investigated in these NSC-explant experiments.
      NSCs derived from the cochlear nucleus engrafted in the brain tissue and
      differentiated into all cells of the neuronal lineage. Hippocampal NSCs also
      immigrated in cochlear nucleus explants and differentiated into neurons,
      astrocytes and oligodendrocytes. Laminin expression was up-regulated in the
      cochlear nucleus whole-mounts and regulated the in vitro differentiation of NSCs
      from the cochlear nucleus. These experiments confirm a neurogenic environment in
      the cochlear nucleus and the capacity of cochlear nucleus-derived NSCs to
      differentiate into neurons and glia. Consequently, the presented results provide
      a first step for the possible application of stem cells to repair the
      disorganization of the cochlear nucleus, which occurs after hearing loss. 

PMID- 25960346
TI  - Structural-functional coupling changes in temporal lobe epilepsy.
AB  - Alterations in both structural connectivity (SC) and functional connectivity (FC)
      have been reported in temporal lobe epilepsy (TLE). However, the relationship
      between FC and SC remains less understood. This study used functional
      connectivity MRI and diffusion tensor imaging to examine coupling of FC and SC
      within the limbic network of TLE, as well as its relation to epilepsy duration,
      regional changes, and disease laterality in 14 patients with left TLE, 10 with
      right TLE, and 11 healthy controls. Structural and functional networks were
      separately constructed and the correlation estimated between structural and
      functional connectivity. This measure of SC-FC coupling was compared between
      left/right TLE and controls, and correlated with epilepsy duration. Elastic net
      regression was used to investigate regional structural and functional changes
      associated with SC-FC coupling. SC-FC coupling was decreased in left TLE compared
      to controls, and accompanied by reductions in FC for left and right TLE and in SC
      for left TLE. When examined in relation to disease duration, an increase in SC-FC
      coupling with longer epilepsy duration was observed, associated predominantly
      with structural loss of the fusiform and frontal inferior orbital gyrus in left
      TLE and functional hub redistribution in right TLE. These results suggest that
      decoupling between structural and functional networks in TLE is modulated by
      several factors, including epilepsy duration and regional changes in the
      fusiform, frontal inferior orbital gyrus, posterior cingulate, and hippocampus.
      SC-FC coupling may provide a more sensitive biomarker of disease burden in TLE
      than biomarkers based on single imaging modalities. 

PMID- 25960348
TI  - Sevoflurane and Isoflurane induce structural changes in brain vascular
      endothelial cells and increase blood-brain barrier permeability: Possible link to
      postoperative delirium and cognitive decline.
AB  - A large percentage of patients subjected to general anesthesia at 65 years and
      older exhibit postoperative delirium (POD). Here, we test the hypothesis that
      inhaled anesthetics (IAs), such as Sevoflurane and Isoflurane, act directly on
      brain vascular endothelial cells (BVECs) to increase blood-brain barrier (BBB)
      permeability, thereby contributing to POD. Rats of young (3-5 months), middle (10
      12 months) and old (17-19 months) ages were anesthetized with Sevoflurane or
      Isoflurane for 3h. After exposure, some were euthanized immediately; others were
      allowed to recover for 24h before sacrifice. Immunohistochemistry was employed to
      monitor the extent of BBB breach, and scanning electron microscopy (SEM) was used
      to examine changes in the luminal surfaces of BVECs. Quantitative
      immunohistochemistry revealed increased BBB permeability in older animals treated
      with Sevoflurane, but not Isoflurane. Extravasated immunoglobulin G showed
      selective affinity for pyramidal neurons. SEM demonstrated marked flattening of
      the luminal surfaces of BVECs in anesthetic-treated rats. Results suggest an
      aging-linked BBB compromise resulting from exposure to Sevoflurane. Changes in
      the luminal surface topology of BVECs indicate a direct effect on the plasma
      membrane, which may weaken or disrupt their BBB-associated tight junctions.
      Disruption of brain homeostasis due to plasma influx into the brain parenchyma
      and binding of plasma components (e.g., immunoglobulins) to neurons may
      contribute to POD. We propose that, in the elderly, exposure to some IAs can
      cause BBB compromise that disrupts brain homeostasis, perturbs neuronal function
      and thereby contributes to POD. If unresolved, this may progress to postoperative
      cognitive decline and later dementia. 

PMID- 25960349
TI  - Functional analysis of potassium channels in Kv7.2 G271V mutant causing early
      onset familial epilepsy.
AB  - Kv7 (KCNQ) channels underlying a class of voltage-gated K+ current are best known
      for regulating neuronal excitability. The first glycine (G) residue in the pore
      helix of Kv7.2 (KCNQ2) subunit is highly conserved among different classes of Kv7
      channel family. A missense mutation causing the replacement of the corresponding
      G residues with a valine (p.G271V) in Kv7.2 was found in a large, four-generation
      pedigree. Here, we set out to examine the molecular pathomechanism of G271V
      mutants using patch clamp technology combined with biochemical and
      immunocytochemical techniques in transiently transfected human embryonic kidney
      (HEK) 293 cells. The expression of Kv7.2 protein had the same intensity for both
      wild type (WT) and G271V. In transfected HEK cells, G271V mutants induced large
      depolarizing shifts of the conductance-voltage relationships and marked slowing
      of current activation kinetics compared to WT. In addition, G271V mutants
      abolished currents in homomeric channels, and resulted in about 50% reduction of
      current in Kv7.2/G271V/Kv7.3 heteromultimeric condition, indicating a more severe
      functional defect. To test for G271V mutant channel expression in surface
      membrane, we performed fluorescence confocal microscopy imaging, which revealed
      no differences between the mutant and WT, suggesting that G271V channels fail to
      open in response to depolarization even though they are present in the membrane.
      Furthermore, pharmacologic intervention experiments revealed that upon specific
      incubation of transfected HEK 293 cells expressing G271V heteromultimeric
      channels in presence of Kv7 channel enhancer retigabine (ezogabine), the
      potassium currents increased significantly, suggesting the potential of
      retigabine as gene-specific therapy.

PMID- 25960350
TI  - Expansion of the lateral ventricles and ependymal deficits underlie the
      hydrocephalus evident in mice lacking the transcription factor NFIX.
AB  - Nuclear factor one X (NFIX) has been shown to play a pivotal role during the
      development of many regions of the brain, including the neocortex, the
      hippocampus and the cerebellum. Mechanistically, NFIX has been shown to promote
      neural stem cell differentiation through the activation of astrocyte-specific
      genes and via the repression of genes central to progenitor cell self-renewal.
      Interestingly, mice lacking Nfix also exhibit other phenotypes with respect to
      development of the central nervous system, and whose underlying causes have yet
      to be determined. Here we examine one of the phenotypes displayed by Nfix(-/-)
      mice, namely hydrocephalus. Through the examination of embryonic and postnatal
      Nfix(-/-) mice we reveal that hydrocephalus is first seen at around postnatal day
      (P) 10 in mice lacking Nfix, and is fully penetrant by P20. Furthermore, we
      examined the subcommissural organ (SCO), the Sylvian aqueduct and the ependymal
      layer of the lateral ventricles, regions that when malformed and functionally
      perturbed have previously been implicated in the development of hydrocephalus.
      SOX3 is a factor known to regulate SCO development. Although we revealed that
      NFIX could repress Sox3-promoter-driven transcriptional activity in vitro, SOX3
      expression within the SCO was normal within Nfix(-/-) mice, and Nfix mutant mice
      showed no abnormalities in the structure or function of the SCO. Moreover, these
      mutant mice exhibited no overt blockage of the Sylvian aqueduct. However, the
      ependymal layer of the lateral ventricles was frequently absent in Nfix(-/-)
      mice, suggesting that this phenotype may underlie the development of
      hydrocephalus within these knockout mice. 

PMID- 25960347
TI  - High-resolution in vivo optical imaging of stroke injury and repair.
AB  - Central nervous system (CNS) function and dysfunction are best understood within
      a framework of interactions between neuronal, glial and vascular compartments
      comprising the neurovascular unit (NVU), all of which contribute to stroke
      induced CNS injury, plasticity, repair, and recovery. Recent advances in in vivo
      optical microscopy have enabled us to observe and interrogate cells and their
      processes with high spatial resolution in real time and in their natural
      environment deep in the brain tissue. Here, we review some of these state-of-the
      art imaging techniques with an emphasis on imaging the interactions among the
      constituents of the NVU during ischemic injury and repair in small animal models.
      This article is part of a Special Issue entitled SI: Cell Interactions In Stroke.

PMID- 25960352
TI  - Repeated fluvoxamine treatment recovers juvenile stress-induced morphological
      changes and depressive-like behavior in rats.
AB  - Human studies have suggested that early life stress such as child abuse could
      enhance susceptibility to depressive disorders. Moreover, the abnormalities of
      the prefrontal cortex have been associated with depression. Although clinical
      studies have implied the negative effects of early life stress on brain
      development, the causality and the detailed morphogenetic changes has not been
      clearly elucidated. In the present study, we determined the effect of juvenile
      stress exposure on the presentation of depressive-like behavior and the neural
      mechanisms involved using a rodent model. Rat pups were exposed to footshock
      stress during postnatal days 21-25 followed by repeated oral administration of
      fluvoxamine (0 or 10mg/kg/d * 14 days), which is a selective serotonin reuptake
      inhibitor. At the postadolescent stage forced swim test assessment of depressive
      like behavior and Golgi-Cox staining of medial prefrontal cortex pyramidal
      neurons followed by morphological analyses were carried out. Post-adolescent
      behavioral and morphological studies identified the presentation of increased
      depressive-like behaviors and reduced spine densities and dendritic lengths of
      layer II/III pyramidal neuron in the infralimbic cortex, but not in the prelimbic
      cortex of rats exposed to juvenile stress. Repeated fluvoxamine treatment
      recovered the increased depressive-like behavior and reduced spine
      densities/dendritic lengths observed in rats exposed to footshock stress.
      Cortical thicknesses in the infralimbic cortex and prelimbic cortex were also
      reduced by juvenile stress, but these reductions were not recovered by
      fluvoxamine treatment. The results demonstrate cortical sensitivities to stress
      exposures during the juvenile stage which mediate behavioral impairments, and
      provide a clue to find therapeutics for early life stress-induced emotional
      dysfunctions.

PMID- 25960353
TI  - Scalable synthesis of the unusual amino acid segment (ADMOA unit) of marine anti
      inflammatory peptide: solomonamide A.
AB  - The most abundantly available hexose sugar, d-glucose has been converted to
      protected 4-amino(2'amino-4'-hydroxy phenyl)-3,5-dihydroxy-2-methyl-6-oxo
      hexanoic acid (protected ADMOA, 3), the unusual amino acid present in marine
      natural product solomonamide A in gram quantities involving easy to operate
      chemical transformations.

PMID- 25960354
TI  - Atomic-scale dynamics of triangular hole growth in monolayer hexagonal boron
      nitride under electron irradiation.
AB  - The production of holes by electron beam irradiation in hexagonal boron nitride
      (hBN), which has a lattice similar to that of graphene, is monitored over time
      using atomic resolution transmission electron microscopy. The holes appear to be
      initiated by the formation of a vacancy of boron and grow in a manner that
      retains an overall triangular shape. The hole growth process involves the
      formation of single chains of B and N atoms and is accompanied by the ejection of
      atoms and bundles of atoms along the hole edges, as well as atom migration. These
      observations are compared to density functional theory calculations and molecular
      dynamics simulations. 

PMID- 25960355
TI  - Urinary extracellular vesicles for biomarker source to monitor polycystic kidney
      disease.
AB  - Extracellular vesicles (EVs) are bilayered lipid vesicles, 50-1000 nm in diameter
      and secreted by most types of cells. They contain many proteins, mRNAs, miRNAs,
      and lipids that reflect the pathophysiological state of the cells they originate
      from, and are therefore considered to be a rich source of potential biomarkers.
      In this issue (Pocsfalvi, G. et al., Proteomics Clin. Appl. 2015, 9, 552-567),
      Pocsfalvi et al. conducted pioneering investigations to determine whether changes
      in the protein content of EVs occur during progression of autosomal dominant
      polycystic kidney disease (ADPKD), a common genetic disorder that predominantly
      affects the kidneys. Most significantly, iTRAQ-based quantitative proteomics
      showed that cytoskeleton-regulating and Ca(2+) -binding proteins are
      differentially expressed in urinary EVs of ADPKD patients. Impressively, these
      proteins are involved in biological processes that are closely related to the
      pathogenic state of tubular epithelial cells in ADPKD, demonstrating the
      possibility to monitor the status of patients using urinary EVs.

PMID- 25960351
TI  - Mechanisms of cell-cell interaction in oligodendrogenesis and remyelination after
      stroke.
AB  - White matter damage is a clinically important aspect of several central nervous
      system diseases, including stroke. Cerebral white matter primarily consists of
      axonal bundles ensheathed with myelin secreted by mature oligodendrocytes, which
      play an important role in neurotransmission between different areas of gray
      matter. During the acute phase of stroke, damage to oligodendrocytes leads to
      white matter dysfunction through the loss of myelin. On the contrary, during the
      chronic phase, white matter components promote an environment, which is favorable
      for neural repair, vascular remodeling, and remyelination. For effective
      remyelination to take place, oligodendrocyte precursor cells (OPCs) play critical
      roles by proliferating and differentiating into mature oligodendrocytes, which
      help to decrease the burden of axonal injury. Notably, other types of cells
      contribute to these OPC responses under the ischemic conditions. This mini-review
      summarizes the non-cell autonomous mechanisms in oligodendrogenesis and
      remyelination after white matter damage, focusing on how OPCs receive support
      from their neighboring cells. This article is part of a Special Issue entitled
      SI: Cell Interactions In Stroke. 

PMID- 25960356
TI  - Improved visibility of brain tumors in synthetic MP-RAGE anatomies with pure T1
      weighting.
AB  - Conventional MRI for brain tumor diagnosis employs T2 -weighted and contrast
      enhanced T1 -weighted sequences. Non-enhanced T1 -weighted images provide
      improved anatomical details for precise tumor location, but reduced tumor-to
      background contrast as elevated T1 and proton density (PD) values in tumor tissue
      affect the signal inversely. Radiofrequency (RF) coil inhomogeneities may further
      mask tumor and edema outlines. To overcome this problem, the aims of this work
      were to employ quantitative MRI techniques to create purely T1 -weighted
      synthetic anatomies which can be expected to yield improved tissue and tumor-to
      background contrasts, to compare the quality of conventional and synthetic
      anatomies, and to investigate optical contrast and visibility of brain tumors and
      edema in synthetic anatomies. Conventional magnetization-prepared rapid
      acquisition of gradient echoes (MP-RAGE) anatomies and maps of T1 , PD and RF
      coil profiles were acquired in comparable and clinically feasible times. Three
      synthetic MP-RAGE anatomies (PD T1 weighting both with and without RF bias; pure
      T1 weighting) were calculated for healthy subjects and 32 patients with brain
      tumors. In healthy subjects, the PD T1 -weighted synthetic anatomies with RF bias
      precisely matched the conventional anatomies, yielding high signal-to-noise (SNR)
      and contrast-to-noise (CNR) ratios. Pure T1 weighting yielded lower SNR, but high
      CNR, because of increased optical contrasts. In patients with brain tumors,
      synthetic anatomies with pure T1 weighting yielded significant increases in
      optical contrast and improved visibility of tumor and edema in comparison with
      anatomies reflecting conventional T1 contrasts. In summary, the optimized purely
      T1 -weighted synthetic anatomy with an isotropic resolution of 1 mm, as proposed
      in this work, considerably enhances optical contrast and visibility of brain
      tumors and edema.

PMID- 25960357
TI  - Maxillomandibular advancement for persistent obstructive sleep apnea after phase
      I surgery in patients without maxillomandibular deficiency. 2000.

PMID- 25960358
TI  - Direction-specific impairments of limits of stability in individuals with
      multiple sclerosis.
AB  - OBJECTIVES: Impaired postural control in individuals with multiple sclerosis (MS)
      is associated with falls. The objective was to evaluate the direction-specific
      limits of stability in people with MS. METHODS: Balance control of 18 individuals
      with relapsing-remitting MS and 18 healthy controls was assessed using
      instrumented (Limits of Stability (LOS) test) and clinical (Berg Balance Scale
      (BBS) and Activities-specific Balance Confidence (ABC) scale) tests. RESULTS:
      There were significant differences in reaction time, movement velocity, endpoint
      excursion, maximum excursion, and directional control measures of the LOS test
      between individuals with MS and healthy controls. The BBS and ABC clinical
      balance measures were significantly lower in individuals with MS compared to
      control subjects. The directional control impairment was seen in the right side
      and backward diagonals (backward-right and backward-left) directions. A
      significant difference between the fallers and non-fallers was found on all the
      components of the LOS test. There was a significant correlation between the BBS
      and ABC scores and different components of the LOS test. CONCLUSIONS: Direction
      specific impairment of limits of stability components was observed in individuals
      with MS. This information could be used in balance rehabilitation of people with
      MS.

PMID- 25960360
TI  - One-pot synthesis and Nb4N5 surface modification of Nb(4+) self-doped KNbO3
      nanorods for enhanced visible-light-driven hydrogen production.
AB  - Herein, rhombohedral self-doped KNbO3 (S-KN) nanorods were fabricated via a one
      pot, solvothermal method without using any surfactant. The presence of Nb(4+) in
      S-KN greatly narrows its band gap and thus extends its photoresponse from UV to
      the visible light region. Moreover, S-KN/Nb4N5 nanorod heterostructures were
      obtained by nitriding S-KN nanorods for different times, which exhibited
      significantly enhanced photocatalytic activity for hydrogen production under
      visible light irradiation. The junction formed between S-KN and Nb4N5 and the
      Nb(4+) self-doping of KN are supposed to be responsible for the enhanced
      photocatalytic activity of S-KN/Nb4N5. This study also paves the way for the
      synthesis of other similar photocatalysts. 

PMID- 25960359
TI  - Synthesis of a heterogeneous artificial metallolipase with chimeric catalytic
      activity.
AB  - A solid-phase strategy using lipase as a biomolecular scaffold to produce a large
      amount of Cu(2+)-metalloenzyme is proposed here. The application of this protocol
      on different 3D cavities of the enzyme allows creating a heterogeneous artificial
      metallolipase showing chimeric catalytic activity. The artificial catalyst was
      assessed in Diels-Alder cycloaddition reactions and cascade reactions showing
      excellent catalytic properties. 

PMID- 25960361
TI  - Photodynamic therapy (PDT) for malignant brain tumors--where do we stand?
AB  - INTRODUCTION: What is the current status of photodynamic therapy (PDT) with
      regard to treating malignant brain tumors? Despite several decades of effort, PDT
      has yet to achieve standard of care. PURPOSE: The questions we wish to answer
      are: where are we clinically with PDT, why is it not standard of care, and what
      is being done in clinical trials to get us there. METHOD: Rather than a meta
      analysis or comprehensive review, our review focuses on who the major research
      groups are, what their approaches to the problem are, and how their results
      compare to standard of care. Secondary questions include what the effective depth
      of light penetration is, and how deep can we expect to kill tumor cells. CURRENT
      RESULTS: A measurable degree of necrosis is seen to a depth of about 5mm.
      Cavitary PDT with hematoporphyrin derivative (HpD) results are encouraging, but
      need an adequate Phase III trial. Talaporfin with cavitary light application
      appears promising, although only a small case series has been reported. Foscan
      for fluorescence guided resection (FGR) plus intraoperative cavitary PDT results
      were improved over controls, but are poor compared to other groups. 5
      Aminolevulinic acid-FGR plus postop cavitary HpD PDT show improvement over
      controls, but the comparison to standard of care is still poor. CONCLUSION:
      Continued research in PDT will determine whether the advances shown will mitigate
      morbidity and mortality, but certainly the potential for this modality to
      revolutionize the treatment of brain tumors remains. The various uses for PDT in
      clinical practice should be pursued.

PMID- 25960362
TI  - [Ultrasound-guided paravertebral block for pyloromyotomy in 3 neonates with
      congenital hypertrophic pyloric stenosis].
AB  - BACKGROUND AND OBJECTIVES: Hypertrophic pyloric stenosis is a relatively common
      affection of gastrointestinal tract in childhood that results in symptoms, such
      as projectile vomiting and metabolic disorders that imply a high risk of
      aspiration during anesthetic induction. In this way, the carrying out of a
      technique with general anesthesia and intravenous rapid sequence induction,
      preoxygenation and cricoid pressure are recommended. After the correction of
      systemic metabolic alkalosis and pH normalization, cerebrospinal fluid can keep a
      state of metabolic alkalosis. This circumstance, in addition to the residual
      effect of neuromuscular blocking agents, inhalant anesthetics and opioids could
      increase the risk of postoperative apnea after a general anesthesia. CASE REPORT:
      We present the successful management in 3 neonates in those a pyloromyotomy was
      carried out because they had presented congenital hypertrophic pyloric stenosis.
      This procedure was done under general anesthesia with orotracheal intubation and
      rapid sequence induction. Then, ultrasound-guided paravertebral block was
      performed as analgesic method without the need for administrating opioids within
      intraoperative period and keeping an appropriate analgesic level. CONCLUSIONS:
      Local anesthesia has demonstrated to be safe and effective in pediatric practice.
      We consider the ultrasound-guided paravertebral block with one dose as a possible
      alternative for other local techniques described, avoiding the use of opioids and
      neuromuscular blocking agents during general anesthesia, and reducing the risk of
      central apnea within postoperative period.

PMID- 25960363
TI  - [Anesthetic management for surgery of esophagus atresia in a newborn with
      Goldenhar's syndrome].
AB  - BACKGROUND AND OBJECTIVES: Goldenhar's syndrome is a polymalformative condition
      consisting of a craniofacial dysostosis that determines difficult airway in up to
      40% of cases. We described a case of a newborn with Goldenhar's syndrome with
      esophageal atresia and tracheoesophageal fistula who underwent repair surgery.
      CASE REPORT: We report the case of a 24-hour-old newborn with Goldenhar's
      syndrome. He had esophageal atresia with distal tracheoesophageal fistula. It was
      decided that an emergency surgery would be performed for repairing it. It was
      carried out under sedation, intubation with fibrobronchoscope distal to the
      fistula, to limit the air flow into the esophagus, and possible abdominal
      distension. Following complete repair of the esophageal atresia and fistula
      ligation, the patient was transferred to the intensive care unit and intubated
      under sedation and analgesia. CONCLUSIONS: The finding of a patient with
      Goldenhar's syndrome and esophageal atresia assumes an exceptional situation and
      a challenge for anesthesiologists, since the anesthetic management depends on the
      patient comorbidity, the type of tracheoesophageal fistula, the usual hospital
      practice and the skills of the anesthesiologist in charge, with the main
      peculiarity being maintenance of adequate pulmonary ventilation in the presence
      of a communication between the airway and the esophagus. Intubation with
      fibrobronchoscope distal to the fistula deals with the management of a probably
      difficult airway and limits the passage of air to the esophagus through the
      fistula.

PMID- 25960364
TI  - Capturing the embryonic stages of self-assembly - design rules for molecular
      computation.
AB  - The drive towards organic computing is gaining momentum. Interestingly, the
      building blocks for such architectures is based on molecular ensembles extending
      from nucleic acids to synthetic molecules. Advancement in this direction requires
      devising precise nanoscopic experiments and model calculations to decipher the
      mechanisms governing the integration of a large number of molecules over time at
      room-temperature. Here, we report on ultrahigh-resolution scanning tunnelling
      microscopic measurements to register the motion of molecules in the absence of
      external stimulus in liquid medium. We observe the collective behavior of
      individual molecules within a swarm which constantly iterate their position to
      attain an energetically favourable site. Our approach provides a consistent
      pathway to register molecular self-assembly in sequential steps from visualising
      thermodynamically driven repair of defects up until the formation of a stable two
      dimensional configuration. These elemental findings on molecular surface
      dynamics, self-repair and intermolecular kinetic pathways rationalised by atom
      scale simulations can be explored for developing new models in algorithmic self
      assembly to realisation of evolvable hardware. 

PMID- 25960365
TI  - 1,2,4-Triphospholyl anions - versatile building blocks for the formation of 1D,
      2D and 3D assemblies.
AB  - The potential of K[P3C2R2] (R = (t)Bu, Mes) as building blocks in metallo
      supramolecular chemistry was investigated and self-assembly processes with Cu(i)
      halides resulted in the formation of a large variety of unprecedented one-, two-
      and even three-dimensional aggregates. The 3D networks showed an interesting
      topological similarity to allotropes of carbon: diamond and the theoretically
      proposed polybenzene. Furthermore, the negative charge of the phospholyl ligand
      favoured the generation of cationic CuaXb (a > b, X = Cl, Br, I) assemblies, a
      challenging area within the well-studied coordination chemistry of CuX units. In
      addition, the 1D strands were also characterized in solution, revealing the
      presence of oligomeric units. 

PMID- 25960366
TI  - A Solomon link through an interwoven molecular grid.
AB  - A molecular Solomon link was synthesized through the assembly of an interwoven
      molecular grid consisting of four bis(benzimidazolepyridyl)benzthiazolo[5,4
      d]thiazole ligands and four zinc(II), iron(II), or cobalt(II) cations, followed
      by ring-closing olefin metathesis. NMR spectroscopy, mass spectrometry, and X-ray
      crystallography confirmed the doubly interlocked topology, and subsequent
      demetalation afforded the wholly organic Solomon link. The synthesis, in which
      each metal ion defines the crossing point of two ligand strands, suggests that
      interwoven molecular grids should be useful scaffolds for the rational
      construction of other topologically complex structures. 

PMID- 25960368
TI  - Pendant ionic groups of conjugated oligoelectrolytes govern their ability to
      intercalate into microbial membranes.
AB  - Conjugated oligoelectrolytes (COEs) bearing pyridinium and carboxylate groups are
      synthesized, characterized, and compared to the trimethylammonium analogue from
      which they are derived. All COEs are able to spontaneously intercalate into
      liposomes, whereas only positively charged COEs intercalate into E. coli
      membranes. Membrane intercalation is determined necessary for performance
      enhancement in microbial fuel cells. 

PMID- 25960367
TI  - High-density waveguide superlattices with low crosstalk.
AB  - Silicon photonics holds great promise for low-cost large-scale photonic
      integration. In its future development, integration density will play an ever
      increasing role in a way similar to that witnessed in integrated circuits.
      Waveguides are perhaps the most ubiquitous component in silicon photonics. As
      such, the density of waveguide elements is expected to have a crucial influence
      on the integration density of a silicon photonic chip. A solution to high-density
      waveguide integration with minimal impact on other performance metrics such as
      crosstalk remains a vital issue in many applications. Here, we propose a
      waveguide superlattice and demonstrate advanced superlattice design concepts such
      as interlacing-recombination that enable high-density waveguide integration at a
      half-wavelength pitch with low crosstalk. Such waveguide superlattices can
      potentially lead to significant reduction in on-chip estate for waveguide
      elements and salient enhancement of performance for important applications,
      opening up possibilities for half-wavelength-pitch optical-phased arrays and
      ultra-dense space-division multiplexing. 

PMID- 25960369
TI  - Relationship of thoracic fat depots with coronary atherosclerosis and circulating
      inflammatory biomarkers.
AB  - OBJECTIVE: The aim of the study was to determine the relationship of various
      thoracic fat depots with the presence and extent of coronary artery plaque and
      circulating biomarkers. METHODS: In 342 patients (52 +/- 11 years, 61% male, BMI
      29.1 +/- 5.9 kg/m(2) ) with coronary computed tomography (CT), angiography, we
      measured the fat volume in four thoracic depots (pericoronary, epicardial,
      periaortic, extracardiac), assessed coronary plaque, and determined the
      circulating levels of C-reactive protein, tumor necrosis factor alpha,
      plasminogen activator inhibitor-1, monocyte chemoattractant protein-1, and
      adiponectin. The extent of coronary plaque was classified into three groups: 0, 1
      3, and >3 segments. RESULTS: Patients with plaque (n =169, 49%) had higher
      volumes of all four fat depots as compared to patients without plaque (all P <
      0.01), despite similar BMI (P = 0.18). Extracardiac fat was most strongly
      correlated with BMI (r = 0.45, P < 0.001), while pericoronary fat was least (r =
      0.21, P < 0.001). Only pericoronary fat remained associated with coronary plaque
      in adjusted analyses. Inflammatory biomarkers showed a positive correlation with
      pericoronary fat (all P < 0.0001), whereas adiponectin was not associated with
      this fat compartment (P = 0.60) and showed a negative correlation with all other
      fat depots (all P < 0.001). CONCLUSIONS: Pericoronary fat is independently
      associated with coronary artery disease (CAD). Its correlation with inflammatory
      biomarkers suggests that while systemic inflammation plays a role in the
      pathogenesis of CAD, there are additional local effects that may exist.

PMID- 25960370
TI  - Velvet-mediated repression of beta-glucan synthesis in Aspergillus nidulans
      spores.
AB  - Beta-glucans are a heterologous group of fibrous glucose polymers that are a
      major constituent of cell walls in Ascomycetes and Basidiomycetes fungi.
      Synthesis of beta (1,3)- and (1,6)-glucans is coordinated with fungal cell growth
      and development, thus, is under tight genetic regulation. Here, we report that
      beta-glucan synthesis in both asexual and sexual spores is turned off by the NF
      kB like fungal regulators VosA and VelB in Aspergillus nidulans. Our genetic and
      genomic analyses have revealed that both VosA and VelB are necessary for proper
      down-regulation of cell wall biosynthetic genes including those associated with
      beta-glucan synthesis in both types of spores. The deletion of vosA or velB
      results in elevated accumulation of beta-glucan in asexual spores. Double mutant
      analyses indicate that VosA and VelB play an inter-dependent role in repressing
      beta-glucan synthesis in asexual spores. In vivo chromatin immuno-precipitation
      analysis shows that both VelB and VosA bind to the promoter region of the beta
      glucan synthase gene fksA in asexual spores. Similarly, VosA is required for
      proper repression of beta-glucan synthesis in sexual spores. In summary, the VosA
      VelB hetero-complex is a key regulatory unit tightly controlling proper levels of
      beta-glucan synthesis in asexual and sexual spores. 

PMID- 25960371
TI  - Comparison of melanoma incidence and trends among youth under 25 years in
      Australia and England, 1990-2010.
AB  - White populations in Australia and England share many genetic and phenotypic
      characteristics due to common ancestry, but Australians experience far higher
      rates of melanoma due to higher ambient ultraviolet radiation (UVR) levels. To
      gain insight into the role of UVR on melanoma development early in life, we used
      national cancer registration data and compared recent incidence rates and long
      term trends of primary invasive cutaneous melanoma in Australian and English
      youth aged 0-24 years diagnosed 1990-2010. Incidence rates and standardized rate
      ratios (SRRs) with 95% confidence intervals (CIs) for 2006-2010 were calculated
      and incidence trends across the whole period were examined using JoinPoint
      regression. In Australian youth, overall melanoma incidence was double that in
      English youth (2.2 and 1.1 per 100,000, respectively). While melanoma rates were
      similarly rare among children <10 years in both countries, in subsequent 5-year
      age groups, incidence was significantly higher in Australia compared to England.
      Melanoma incidence among 15-24 year olds significantly increased by more than 2%
      per year in both sexes in England. However, after an initial non-significant
      increase, Australian rates for this older age group significantly decreased by
      6.0% (95% CI, -8.2 to -3.8) per year in females from 1997 and decreased by 12.4%
      (95% CI, -20.3 to -3.8) per year in males from 2004. Long-standing primary
      prevention strategies targeted at curbing UVR exposure appear to have been
      effective in mitigating incidence trends in Australian youth, but decreases in
      incidence in English youth are yet to be observed. 

PMID- 25960373
TI  - [P3Se4](+): A Binary Phosphorus-Selenium Cation.
AB  - Although a fairly large number of binary group 15/16 element cations have been
      reported, no example involving phosphorus in combination with a group 16 element
      has been synthesized and characterized to date. In this contribution is reported
      the synthesis and structural characterization of the first example of such a
      cation, namely a nortricyclane-type [P3Se4](+). This cation has been
      independently discovered by three groups through three different synthetic
      routes, as described herein. The molecular and electronic structure of the
      [P3Se4](+) cage and its crystal properties in the solid state have been
      characterized comprehensively by using X-ray diffraction, Raman, and nuclear
      magnetic resonance spectroscopies, as well as quantum chemical calculations.

PMID- 25960372
TI  - Claudins and pathogenesis of viral infection.
AB  - Since their discovery, tremendous progress has been made in our understanding of
      the roles of claudins in tight junction physiology. In addition, interactions
      between claudins and other cellular proteins have highlighted their novel roles
      in cell physiology. Moreover, the importance of claudins is becoming apparent in
      the pathophysiology of several diseases, including viral infections. Notable is
      the discovery of CLDN1 as an essential host factor for hepatitis C virus (HCV)
      entry, which led to detailed characterization of CLDN1 and its association with
      tetraspanin CD81 for the initiation of HCV infection. CLDN1 has also been shown
      to facilitate dengue virus entry. Furthermore, owing to the roles of claudins in
      forming anatomical barriers, several viruses have been shown to alter claudin
      expression at the tight junction. This review summarizes the role of claudins in
      viral infection, with particular emphasis on HCV. 

PMID- 25960374
TI  - School context, friendship ties and adolescent mental health: A multilevel
      analysis of the Korean Youth Panel Survey (KYPS).
AB  - Research on the social determinants of health suggests that interpersonal
      networks play a critical role in facilitating individual mental and physical well
      being. Prior studies also indicate that ecological or contextual factors
      contribute to positive health outcomes. This study extends prior research by
      examining the factors associated with adolescent health in an Asian context.
      Based on the multilevel analysis of the Korean Youth Panel Survey (2006 & 2007),
      a longitudinal project funded by the Korean government, it investigates some of
      the key variables related to the mental health of Korean students. Much of
      previous research focuses on the functions of social capital. This study
      contributes to the social epidemiology literature by investigating the possible
      downside of network ties. Specifically, it asks whether having delinquent friends
      is associated with negative mental health experiences. In addition, little
      research has been conducted concerning the associations between adolescent health
      outcomes and school characteristics. This study moves in that direction by
      examining the relationship between mental well-being of students and a variety of
      school related variables (e.g., subjective attitude toward school and quality of
      relationship with peers and teachers). Hierarchical linear modeling shows that,
      among the social capital control variables, being properly integrated into the
      family and frequent peer interaction significantly add to mental health. At the
      individual (student) level only, ties to delinquent friends are negatively
      associated with mental health, while at both individual and contextual levels,
      school characteristics are positively related to adolescent subjective well
      being. 

PMID- 25960375
TI  - Validation of the appropriate use criteria for percutaneous coronary intervention
      in patients with stable coronary artery disease (from the COURAGE trial).
AB  - Establishing the validity of appropriate use criteria (AUC) for percutaneous
      coronary intervention (PCI) in the setting of stable ischemic heart disease can
      support their adoption for quality improvement. We conducted a post hoc analysis
      of 2,287 Clinical Outcomes Utilizing Revascularization and Aggressive Drug
      Evaluation trial patients with stable ischemic heart disease randomized to PCI
      with optimal medical therapy (OMT) or OMT alone. Within appropriateness
      categories, we compared rates of death, myocardial infarction, revascularization
      subsequent to initial therapy, and angina-specific health status as determined by
      the Seattle Angina Questionnaire in patients randomized to PCI + OMT to those
      randomized to OMT alone. A total of 1,987 patients (87.9%) were mapped to the
      2012 publication of the AUC, with 1,334 (67.1%) classified as appropriate, 551
      (27.7%) uncertain, and 102 (5.1%) as inappropriate. There were no significant
      differences between PCI and OMT alone in the rate of mortality and myocardial
      infarction by appropriateness classification. Rates of revascularization were
      significantly lower in patients initially receiving PCI + OMT who were classified
      as appropriate (hazard ratio 0.65; 95% confidence interval 0.53 to 0.80; p
      <0.001) or uncertain (hazard ratio 0.49; 95% confidence interval 0.32 to 0.76; p
      = 0.001). Furthermore, among patients classified as appropriate by the AUC,
      Seattle Angina Questionnaire scores at 1 month were better in the PCI-treated
      group compared with the medical therapy group (80 +/- 23 vs 75 +/- 24 for angina
      frequency, 73 +/- 24 vs 68 +/- 24 for physical limitations, and 68 +/- 23 vs 60
      +/- 24 for quality of life; all p <0.01), with differences generally persisting
      through 12 months. In contrast, health status scores were similar throughout the
      first year of follow-up in PCI + OMT patients compared with OMT alone in patients
      classified as uncertain or inappropriate. In conclusion, these findings support
      the validity of the AUC in efforts to improve health care quality through optimal
      use of PCI.

PMID- 25960376
TI  - Cardiorespiratory Fitness as a Prognostic Factor in Heart Failure Needs to be
      Standardized for Body Composition.

PMID- 25960377
TI  - Effect of gender on results of percutaneous edge-to-edge mitral valve repair with
      MitraClip system.
AB  - Knowledge regarding gender-specific results of percutaneous edge-to-edge mitral
      valve repair is scarce. The aim of this study was to investigate gender
      differences in outcomes in a cohort of patients treated with MitraClip
      implantation. A multicenter registry of 173 patients treated with MitraClip
      prostheses from 2009 to 2012 at 3 experienced centers was performed. One hundred
      nine patients (63%) were men. Men were younger (mean age 73 +/- 10 vs 79 +/- 9
      years, p = 0.001) and had a higher prevalence of previous coronary bypass graft
      surgery (34% vs 13%, p = 0.002), previous myocardial infarction (46% vs 20%, p =
      0.001), and diabetes mellitus (26% vs 11%, p = 0.020). There were no differences
      regarding New York Heart Association (NYHA) functional class before the
      intervention (NYHA class III or IV in 95% of men vs 97% of women, p = 0.472) or
      the cause of mitral regurgitation (MR) (functional in 58% of men vs 48% of women,
      p = 0.233). Men exhibited significantly larger ventricles (mean indexed left
      ventricular end-systolic diameter 2.4 +/- 0.8 vs 2.0 +/- 1.6 cm/m(2), p = 0.002,
      and mean indexed left ventricular end-diastolic volume 92.7 +/- 46.1 vs 59.9 +/-
      24.6 ml/m(2), p <0.001). At 1 month, there were no differences between groups in
      the reduction of MR or NYHA functional class (MR grade <=2+ in 98.2% of men vs
      96.8% of women, p = 0.586, and NYHA class <=II in 78.3% of men vs 77% of women, p
      = 0.851). At 6 months, results were maintained (MR grade <=2+ in 89.5% of men vs
      96.8% of women, p = 0.414, and NYHA class <=II in 73.1% of men vs 74.2% of women,
      p = 0.912). After a mean follow-up period of 16.1 +/- 11.1 months, no difference
      was found between groups in the incidence of death or admission for heart failure
      (log-rank p = 0.798). In conclusion, MitraClip implantation seems to be an
      equally safe and effective treatment of MR in men and women.

PMID- 25960378
TI  - Meta-analysis of long-term clinical outcomes of everolimus-eluting stents.
AB  - The superiority of everolimus-eluting stents (EES) over sirolimus-eluting stents
      (SES) for long-term clinical outcomes has not been yet firmly established. We
      conducted a systematic review and a meta-analysis of randomized controlled trials
      (RCTs) comparing EES directly with SES using the longest available follow-up
      data. We searched PubMed, the Cochrane database, and ClinicalTrials.gov for RCTs
      comparing outcomes between EES and SES and identified 13,434 randomly assigned
      patients from 14 RCTs. EES was associated with significantly lower risks than SES
      for definite stent thrombosis (ST), definite/probable ST, target-lesion
      revascularization (TLR), and major adverse cardiac events (MACE). The risks for
      all-cause death and myocardial infarction were similar between EES and SES. By
      the stratified analysis according to the timing after stent implantation, the
      favorable trend of EES relative to SES for ST, TLR, and MACE was consistently
      observed both within and beyond 1 year. The lower risk of EES relative to SES for
      MACE beyond 1 year was statistically significant (pooled odds ratio 0.77, 95%
      confidence interval 0.61 to 0.96, p = 0.02). In conclusion, the current meta
      analysis of 14 RCTs directly comparing EES with SES suggested that EES provided
      improvement in both safety and efficacy; EES compared with SES was associated
      with significantly lower risk for definite ST, definite/probable ST, TLR, and
      MACE. The direction and magnitude of the effect beyond 1 year were comparable
      with those observed within 1 year. 

PMID- 25960379
TI  - Usefulness of fetuin-A to predict risk for cardiovascular disease among patients
      with obstructive sleep apnea.
AB  - Patients with obstructive sleep apnea (OSA) are at increased risk for
      cardiovascular diseases (CVDs). Fetuin-A, a novel hepatokine, has been associated
      with the metabolic syndrome (MetS), insulin resistance, and type 2 diabetes
      mellitus, all of which are highly prevalent in patients with OSA and associated
      with increased CVD risk. The goal of this study was to determine whether fetuin-A
      could be involved in the pathogenesis of CVD risk in patients with OSA, through
      relations of fetuin-A with MetS components and/or insulin resistance. Overweight
      or obese, nondiabetic volunteers (n = 120) were diagnosed with OSA by in
      laboratory nocturnal polysomnography. Steady-state plasma glucose concentrations
      derived during the insulin suppression test were used to quantify insulin
      mediated glucose uptake; higher steady-state plasma glucose concentrations
      indicated greater insulin resistance. Fasting plasma fetuin-A and lipoprotein
      concentrations were measured. Whereas neither the prevalence of MetS nor the
      number of MetS components was associated with tertiles of fetuin-A
      concentrations, the lipoprotein components of MetS, triglycerides and high
      density lipoprotein cholesterol, increased (p <0.01) and decreased (p <0.05),
      respectively, across fetuin-A tertiles. Additionally, comprehensive lipoprotein
      analysis revealed that very low density lipoprotein (VLDL) particles and VLDL
      subfractions (VLDL1+2 and VLDL3) were increased across fetuin-A tertiles. In
      contrast, neither insulin resistance nor sleep measurements related to OSA were
      found to be modified by fetuin-A concentrations. In conclusion, abnormalities of
      lipoprotein metabolism, but not MetS or insulin resistance per se, may represent
      a mechanism by which fetuin-A contributes to increased CVD risk in patients with
      OSA.

PMID- 25960380
TI  - Did Colchicine Prove Useful in the Prevention of Postoperative Atrial
      Fibrillation?

PMID- 25960382
TI  - Reply: To PMID 25784519.

PMID- 25960381
TI  - Leukocyte telomere length and coronary artery calcium.
AB  - Patients with histories of myocardial infarction display shortened leukocyte
      telomere length (LTL), but conflicting findings have been reported on the
      relation between LTL and subclinical coronary artery atherosclerosis, as
      expressed by coronary artery calcium (CAC). The aim of this study was to examine
      the relation between LTL, measured by Southern blots, and CAC in 3,169
      participants in the National Heart, Lung, and Blood Institute Family Heart Study.
      Participants consisted of 2,556 whites, 613 blacks, 1,790 women, and 1,379 men.
      The odds of having CAC >=100 for the shortest LTL tertile versus the longest LTL
      tertile were 1.95 (95% confidence interval [CI] 1.28 to 3.16) in white men and
      1.76 (95% CI 1.18 to 2.45) in white women, after adjusting for multiple
      covariates of CAC. The corresponding odds ratios for blacks were 1.53 (95% CI
      0.67 to 3.50) and 0.87 (95% CI 0.37 to 2.00). Significance levels of tests for
      trend across LTL tertiles were p = 0.002 in white men, p = 0.006 in white women,
      p = 0.32 in black men, and p = 0.74 in black women. The associations, or lack of
      associations, were independent of C-reactive protein levels and other risk
      factors for CAC. As previously shown in other studies, whites displayed shorter
      LTLs than blacks (p <0.0001). In conclusion, the higher the coronary artery
      atherosclerotic burden in whites, the shorter the LTL. This LTL-atherosclerosis
      connection is not found in blacks. The mechanisms for the racial difference in
      LTL, CAC, and their interrelations do not seem to be related to inflammation and
      merit further research. 

PMID- 25960383
TI  - [Item 322 - UE 10 Iatrogenicity. Diagnosis and Prevention: Drug toxidermia].

PMID- 25960385
TI  - Risk factors for extensive drug-resistance and mortality in geriatric inpatients
      with bacteremia caused by Acinetobacter baumannii.
AB  - BACKGROUND: The aim of this study was to explore the risk factors for developing
      bacteremia caused by extensive drug-resistant (XDR) Acinetobacter baumannii and
      the associated mortality in geriatric inpatients. METHODS: We conducted a
      retrospective study of 125 patients with A baumannii bacteremia between October
      2008 and December 2013 at a medical center in China. RESULTS: The 30-day hospital
      mortality rate was 55.2%. XDR A baumannii was detected in 31.2% of all cases. A
      logistic regression analysis suggested that chronic obstructive pulmonary
      disease, a bedridden status, and central venous catheters were associated with
      bacteremia caused by XDR A baumannii, with adjusted odds ratios (aORs) and 95%
      confidence intervals (CIs) of 2.59 (1.01-6.64), 4.08 (1.39-12.01), and 9.52 (1.90
      47.56), respectively. Furthermore, intensive care unit (ICU) stay, bacteremia
      caused by XDR A baumannii, concurrent fungal infection, and age (70-80 years old
      and >80 years old) were associated with mortality, with aORs and 95% CIs of 3.16
      (1.29-7.73), 4.01 (1.46-11.04), 3.20 (1.28-7.98), 4.31 (1.44-12.92), and 5.46
      (1.94-15.35), respectively. CONCLUSION: Bacteremia is associated with a high 30
      day hospital mortality rate in geriatric inpatients. Furthermore, ICU stay,
      bacteremia caused by XDR A baumannii, concurrent fungal infection, and age are
      associated with increased mortality in geriatric inpatients with A baumannii
      bacteremia.

PMID- 25960384
TI  - Building-level analyses to prospectively detect influenza outbreaks in long-term
      care facilities: New York City, 2013-2014.
AB  - BACKGROUND: Timely outbreak detection is necessary to successfully control
      influenza in long-term care facilities (LTCFs) and other institutions. To
      supplement nosocomial outbreak reports, calls from infection control staff, and
      active laboratory surveillance, the New York City (NYC) Department of Health and
      Mental Hygiene implemented an automated building-level analysis to proactively
      identify LTCFs with laboratory-confirmed influenza activity. METHODS: Geocoded
      addresses of LTCFs in NYC were compared with geocoded residential addresses for
      all case-patients with laboratory-confirmed influenza reported through passive
      surveillance. An automated daily analysis used the geocoded building
      identification number, approximate text matching, and key-word searches to
      identify influenza in residents of LTCFs for review and follow-up by surveillance
      coordinators. Our aim was to determine whether the building analysis improved
      prospective outbreak detection during the 2013-2014 influenza season. RESULTS: Of
      119 outbreaks identified in LTCFs, 109 (92%) were ever detected by the building
      analysis, and 55 (46%) were first detected by the building analysis. Of the 5,953
      LTCF staff and residents who received antiviral prophylaxis during the 2013-2014
      season, 929 (16%) were at LTCFs where outbreaks were initially detected by the
      building analysis. CONCLUSIONS: A novel building-level analysis improved
      influenza outbreak identification in LTCFs in NYC, prompting timely infection
      control measures.

PMID- 25960386
TI  - Macromolecular crowding: Macromolecules friend or foe.
AB  - BACKGROUND: Cellular interior is known to be densely crowded due to the presence
      of soluble and insoluble macromolecules, which altogether occupy ~40% of the
      total cellular volume. This results in altered biological properties of
      macromolecules. SCOPE OF REVIEW: Macromolecular crowding is observed to have both
      positive and negative effects on protein folding, structure, stability and
      function. Significant data has been accumulated so far on both the aspects.
      However, most of the review articles so far have focused on the positive aspect
      of macromolecular crowding and not much attention has been paid on the
      deleterious aspect of crowding on macromolecules. In order to have a complete
      knowledge of the effect of macromolecular crowding on proteins and enzymes, it is
      important to look into both the aspects of crowding to determine its precise role
      under physiological conditions. To fill the gap in the understanding of the
      effect of macromolecular crowding on proteins and enzymes, this review article
      focuses on the deleterious influence of crowding on macromolecules. MAJOR
      CONCLUSIONS: Macromolecular crowding is not always good but also has several
      deleterious effects on various macromolecular properties. Taken together, the
      properties of biological macromolecules in vivo appears to be finely regulated by
      the nature and level of the intracellular crowdedness in order to perform their
      biological functions appropriately. GENERAL SIGNIFICANCE: The information
      provided here gives an understanding of the role played by the nature and level
      of cellular crowdedness in intensifying and/or alleviating the burden of various
      proteopathies.

PMID- 25960387
TI  - IDH1, lipid metabolism and cancer: Shedding new light on old ideas.
AB  - BACKGROUND: Since the initial discovery of mutations in the isocitrate
      dehydrogenase 1 (IDH1) gene in a large subset of human low-grade gliomas and
      acute myelogenous leukemia (AML), much interest focused on the function of IDH1
      and on the relationship between mutations in IDH1 and tumor progression. To date,
      mutations in the IDH1 gene have been found in numerous cancers with the highest
      frequencies occurring in gliomas, chondrosarcomas/enchondromas and
      cholangiocarcinomas. SCOPE OF REVIEW: IDH1 was first described in the scientific
      literature as early as 1950. Early researchers proposed that the enzyme likely
      functions in cellular lipid metabolism based on the observation that the
      enzymatic reaction produces NADPH and partially localizes to peroxisomes. This
      article highlights the studies implicating IDH1 in cytoplasmic and peroxisomal
      lipid metabolism from the early researchers to the recent studies examining
      mutant IDH1(R132), the most common IDH1 mutation found in cancer. MAJOR
      CONCLUSIONS: While a role for IDH1 in lipid biosynthesis in the liver and adipose
      tissue is now established, a role in lipid metabolism in the brain and tumors is
      beginning to be examined. The recent discoveries that IDH1(R132H) interferes with
      the metabolism of phospholipids in gliomas and that IDH1 activity could
      participate in the synthesis of acetyl-CoA from glutamine in hypoxic tumors
      highlight roles for IDH1 in lipid metabolism in a broad spectrum of tissues.
      GENERAL SIGNIFICANCE: Interferences in cytoplasmic and peroxisomal lipid
      metabolism by IDH1(R132) may contribute to the more favorable clinical outcome in
      patients whose tumors express mutations in the IDH1 gene.

PMID- 25960388
TI  - Lichen endophyte derived pyridoxatin inactivates Candida growth by interfering
      with ergosterol biosynthesis.
AB  - BACKGROUND: This study is to characterize the antifungal effects of pyridoxatin
      (PYR), a small natural product isolated from an endolichenic fungus. METHODS: The
      susceptibility tests in vitro and in vivo by using Caenorhabditis elegans as an
      infectious model were performed to evaluate the antifungal efficacy of PYR
      against Candida species. The cytotoxicity of PYR against normal human cells was
      tested using MTT assay. The transcriptional levels of genes related to sterol
      synthesis and cell cycle regulation were measured using real-time quantitative
      PCR (qPCR). The contents ergosterol, squalene, lanosterol were detected by liquid
      chromatography/tandem mass spectrometry (LC/MS). RESULTS: PYR was effective
      against four tested Candida species with its minimal inhibitory concentrations
      (MICs) ranging from 1-4MUg/ml. No obvious cytotoxicity was observed for PYR
      against normal human cells. PYR inhibited the growth of Candida albicans,
      preventing the biofilm formation. And the antifungal action was independent on
      efflux pumps. The in vivo test showed PYR greatly prolonged the survival of
      infected C. elegans. qPCR results revealed that most of the genes related to
      sterol biosynthesis were considerably down-regulated in PYR-treated cells.
      Determination of the sterol content found that PYR inhibited the ergosterol
      synthesis dose dependently and caused the accumulation of squalene and
      lanosterol. Moreover, analysis of the structure-activity relationship revealed
      the heterocyclic hydroxamic acid in PYR was the key group for the antifungal
      action. CONCLUSIONS: PYR interferes with the ergosterol synthesis to exert
      antifungal action. GENERAL SIGNIFICANCE: The elucidated mechanism provides
      possible applications of PYR in fighting clinical relevant fungal infections.

PMID- 25960389
TI  - Post-translational modification of a chimeric EPO-Fc hormone is more important
      than its molecular size in defining its in vivo hematopoietic activity.
AB  - BACKGROUND: Recombinant erythropoietin (EPO) has been marketed as
      biopharmaceutical for anemia and chronic renal failure. Long-acting EPO variants
      that aimed at achieving less frequent dosing have been generated, either by the
      addition of glycosylation sites or increasing its molecular weight. METHODS: The
      hEPO cDNA linked to the human IgG Fc fragment was cloned as a single codifying
      gene on the pAdtrack-CMV vector, yielding the recombinant adenoviral genome. For
      in vitro and in vivo expression assays cervical cancer cell line (SiHa) and
      nulliparous goats were used, respectively. The hematopoietic activity of EPO-Fc,
      expressed as the differential increment of hematocrit was evaluated in B6D2F1
      mice. NP-HPLC of the 2AB-labeled N-glycan was carried out to profile analysis.
      RESULTS: The direct transduction of mammary secretory cells with adenoviral
      vector is a robust methodology to obtain high levels of EPO of up to 3.5mg/mL in
      goat's milk. SiHa-derived EPO-Fc showed significant improvement in hematopoietic
      activity compared to the commercial hEPO counterpart or with the homologous milk
      derived EPO-Fc. The role of the molecular weight seemed to be important in
      enhancing the hematopoietic activity of SiHa-derived EPO-Fc. However, the lack of
      sialylated multi-antennary glycosylation profile in milk-derived EPO-Fc resulted
      in lower biological activity. CONCLUSIONS: The low content of tri- or tetra
      antennary sialylated N-glycans linked to the chimeric EPO-Fc hormone, expressed
      in the goat mammary gland epithelial cells, defined its in vivo hematopoietic
      activity. GENERAL SIGNIFICANCE: The sialylated N-glycan content plays a more
      significant role in the in vivo biological activity of hEPO than its increased
      molecular weight.

PMID- 25960390
TI  - Apocrine secretion: New insights into an old phenomenon.
AB  - BACKGROUND: While apocrine secretion was among the earliest secretory mechanisms
      to be identified, its underlying basis remains poorly understood. SCOPE OF
      REVIEW: This review reappraises our understanding of apocrine secretion using
      insights about apocrine secretion from the salivary glands of Drosophila, in
      which molecular genetic analyses have provided a glimmer of hope for elucidating
      the mechanistic aspects of this fundamental process. MAJOR CONCLUSIONS: In
      contrast to the well-defined process of exocytosis, apocrine secretion is non
      vesicular transport and secretory pathway that entails the loss of part of the
      cytoplasm. It often involves apical protrusions and generates cytoplasmic
      fragments inside a secretory lumen. In its most intense phase this process is
      accompanied by the release of large fragments of cellular structures and entire
      organelles that include mitochondria, Golgi, and portions of the endoplasmic
      reticulum, among others. Proteomic analyses revealed that the secretion is
      composed of hundreds to thousands of membranous, cytoskeletal, microsomal,
      mitochondrial, ribosomal, and even nuclear as well as nucleolar proteins.
      Strikingly, although many nuclear proteins are released, the nuclear
      deoxyribonucleic acid itself remains intact. In spite of this complexity, it
      appears that several protein components of apocrine secretion are identical,
      regardless of the location of the apocrine gland. GENERAL SIGNIFICANCE: This type
      of secretion appears to be common to many, if not all, barrier epithelial tissues
      including skin derivatives and the epididymis, and is implicated also in
      lung/bronchi and intestinal epithelium. Apocrine secretion is a mechanism that
      provides the en masse delivery of a very complex proteinaceous mixture from
      polarized epithelial tissues to allow for communication at exterior interfaces.

PMID- 25960391
TI  - A novel anti-microtubule agent with carbazole and benzohydrazide structures
      suppresses tumor cell growth in vivo.
AB  - BACKGROUND: The mitotic spindles are among the most successful targets of anti
      cancer chemotherapy, and they still hold promise as targets for novel drugs. The
      anti-mitotic drugs in current clinical use, including taxanes, epothilones, vinca
      alkaloids, and halichondrins, are all microtubule-targeting agents. Although
      these drugs are effective for cancer chemotherapy, they have some critical
      problems; e.g., neurotoxicity caused by damage to neuronal microtubules, as well
      as innate or acquired drug resistance. To overcome these problems, a great deal
      of effort has been expended on development of novel anti-mitotics. METHODS: We
      identified novel microtubule-targeting agents with carbazole and benzohydrazide
      structures: N'-[(9-ethyl-9H-carbazol-3-yl)methylene]-2-methylbenzohydrazide (code
      number HND-007) and its related compounds. We investigated their activities
      against cancer cells using various methods including cell growth assay,
      immunofluorescence analysis, cell cycle analysis, tubulin polymerization assay,
      and tumor inhibition assay in nude mice. RESULTS: HND-007 inhibits tubulin
      polymerization in vitro and blocks microtubule formation and centrosome
      separation in cancer cells. Consequently, it suppresses the growth of various
      cancer cell lines, with IC50 values in the range 1.3-4.6MUM. In addition, HND-007
      can inhibit the growth of taxane-resistant cancer cells that overexpress P
      glycoprotein. Finally, HND-007 can inhibit HeLa cell tumor growth in nude mice.
      CONCLUSIONS AND GENERAL SIGNIFICANCE: Taken together, these findings suggest that
      HND-007 is a promising lead compound for development of novel anti-mitotic, anti
      microtubule chemotherapeutic agents.

PMID- 25960392
TI  - Evaluating Industry Self-Regulation of Food Marketing to Children.
AB  - INTRODUCTION: Concern has grown about the role of televised food advertising as a
      contributor to childhood obesity. In response, the food industry adopted a
      program of self-regulation, with participating companies pledging to limit child
      targeted advertising to healthier products. The implicit promise of the industry
      initiative is a significant improvement in the overall nutritional quality of
      foods marketed to children, thereby negating the need for governmental regulation
      to accomplish that objective. This study assesses the efficacy of industry self
      regulation by comparing advertising content on children's TV programs before and
      after self-regulation was implemented. METHODS: A systematic content analysis of
      food advertisements (n=625 in 2007, n=354 in 2013) appearing in children's TV
      programs on the most popular cable and broadcast channels was conducted. RESULTS:
      All analyses were conducted in 2014. Findings indicated that no significant
      improvement in the overall nutritional quality of foods marketed to children has
      been achieved since industry self-regulation was adopted. In 2013, 80.5% of all
      foods advertised to children on TV were for products in the poorest nutritional
      category, and thus pose high risk for contributing to obesity. CONCLUSIONS: The
      lack of significant improvement in the nutritional quality of food marketed to
      children is likely a result of the weak nutritional standards for defining
      healthy foods employed by industry, and because a substantial proportion of child
      oriented food marketers do not participate in self-regulation. The lack of
      success achieved by self-regulation indicates that other policy actions are
      needed to effectively reduce children's exposure to obesogenic food advertising.

PMID- 25960393
TI  - Looking Beyond Income and Education: Socioeconomic Status Gradients Among Future
      High-Cost Users of Health Care.
AB  - INTRODUCTION: Healthcare spending occurs disproportionately among a very small
      portion of the population. Research on these high-cost users (HCUs) of health
      care has been overwhelmingly cross-sectional in nature and limited to the few
      sociodemographic and clinical characteristics available in health administrative
      databases. This study is the first to bridge this knowledge gap by applying a
      population health lens to HCUs. We investigate associations between a broad range
      of SES characteristics and future HCUs. METHODS: A cohort of adults from two
      cycles of large, nationally representative health surveys conducted in 2003 and
      2005 was linked to population-based health administrative databases from a
      universal healthcare plan for Ontario, Canada. Comprehensive person-centered
      estimates of annual healthcare spending were calculated for the subsequent 5
      years following interview. Baseline HCUs (top 5%) were excluded and healthcare
      spending for non-HCUs was analyzed. Adjusted for predisposition and need factors,
      the odds of future HCU status (over 5 years) were estimated according to various
      individual, household, and neighborhood SES factors. Analyses were conducted in
      2014. RESULTS: Low income (personal and household); less than post-secondary
      education; and living in high-dependency neighborhoods greatly increased the odds
      of future HCUs. After adjustment, future HCU status was most strongly associated
      with food insecurity, personal income, and non-homeownership. Living in highly
      deprived or low ethnic concentration neighborhoods also increased the odds of
      becoming an HCU. CONCLUSIONS: Findings suggest that addressing social
      determinants of health, such as food and housing security, may be important
      components of interventions aiming to improve health outcomes and reduce costs.

PMID- 25960394
TI  - Change in Neighborhood Socioeconomic Status and Weight Gain: Dallas Heart Study.
AB  - INTRODUCTION: Despite a proposed connection between neighborhood environment and
      obesity, few longitudinal studies have examined the relationship between change
      in neighborhood socioeconomic deprivation, as defined by moving between
      neighborhoods, and change in body weight. The purpose of this study is to examine
      the longitudinal relationship between moving to more socioeconomically deprived
      neighborhoods and weight gain as a cardiovascular risk factor. METHODS: Weight
      (kilograms) was measured in the Dallas Heart Study (DHS), a multiethnic cohort
      aged 18-65 years, at baseline (2000-2002) and 7-year follow-up (2007-2009,
      N=1,835). Data were analyzed in 2013-2014. Geocoded addresses were linked to
      Dallas County, TX, census block groups. A block group-level neighborhood
      deprivation index (NDI) was created. Multilevel difference-in-difference models
      with random effects and a Heckman correction factor (HCF) determined weight
      change relative to NDI change. RESULTS: Forty-nine percent of the DHS population
      moved (263 to higher NDI, 586 to lower NDI, 47 within same NDI), with blacks more
      likely to move than whites or Hispanics (p<0.01), but similar baseline BMI and
      waist circumference were observed in movers versus non-movers (p>0.05). Adjusting
      for HCF, sex, race, and time-varying covariates, those who moved to areas of
      higher NDI gained more weight compared to those remaining in the same or moving
      to a lower NDI (0.64 kg per 1-unit NDI increase, 95% CI=0.09, 1.19). Impact of
      NDI change on weight gain increased with time (p=0.03). CONCLUSIONS: Moving to
      more-socioeconomically deprived neighborhoods was associated with weight gain
      among DHS participants.

PMID- 25960395
TI  - Responses to a Decision Aid on Prostate Cancer Screening in Primary Care
      Practices.
AB  - INTRODUCTION: Prostate-specific antigen (PSA) testing remains controversial, with
      most guidelines recommending shared decision making. This study describes men's
      PSA screening preferences before and after viewing a decision aid and relates
      these preferences to subsequent clinician visit content. METHODS: Men were
      recruited from two health systems in 2009-2013. Participants answered a
      questionnaire before and after decision aid viewing addressing PSA screening
      preferences and five basic knowledge questions. At one health system,
      participants also answered a survey after a subsequent clinician visit. Data were
      analyzed in 2014. RESULTS: One thousand forty-one predominantly white, well
      educated men responded to the pre- and post-viewing questionnaire (25% and 29%
      response rates at the two sites). After viewing, the proportion of patients
      leaning away from PSA screening increased significantly (p<0.001), with 386 (38%)
      leaning toward PSA screening versus 436 (43%) before viewing; 174 (17%) unsure
      versus 319 (32%) before; and 448 (44%) leaning away versus 253 (25%) before.
      Higher knowledge scores were associated with being more likely to lean against
      screening and less likely to be unsure (p<0.001). Among 278 men who also
      completed a questionnaire after a subsequent clinician visit, participants who
      planned to discuss PSA screening with their clinicians were significantly more
      likely to report such discussions than participants who did not (148/217 [68%] vs
      16/46 [35%], respectively [p<0.001]). CONCLUSIONS: A decision aid reduces men's
      interest in PSA screening, particularly among the initially unsure. Men who plan
      to discuss PSA screening with their clinician after a decision aid are more
      likely to do so.

PMID- 25960396
TI  - RING E3-Catalyzed E2 Self-Ubiquitination Attenuates the Activity of Ube2E
      Ubiquitin-Conjugating Enzymes.
AB  - Ubiquitination of a target protein is accomplished through sequential actions of
      the E1, E2s, and the E3s. E2s dictate the modification topology while E3 ligases
      confer substrate specificity and recruit the cognate E2. Human genome codes for
      ~35 different E2 proteins; all of which contain the characteristic ubiquitin
      conjugating UBC core domain sufficient for catalysis. Many of these E2 enzymes
      also have N- or C-terminal extensions; roles of which are not very well
      understood. We show that the N-terminal extension of Ube2E1 undergoes
      intramolecular auto-ubiquitination. This self-ubiquitination activity is enhanced
      in the presence of interacting RING E3 ligases and results in a progressive
      attenuation of the E2 activity toward substrate/E3 modification. We also find
      that the N-terminal ubiquitination sites are conserved in all the three Ube2Es
      and replacing them with arginine renders all three full-length Ube2Es equally
      active as their core UBC domains. Based on these results, we propose that E3
      catalyzed self-ubiquitination acts as a key regulatory mechanism that controls
      the activity of Ube2E class of ubiquitin E2s. 

PMID- 25960397
TI  - Activation of phosphatidylinositol 3-kinase beta by the platelet collagen
      receptors integrin alpha2beta1 and GPVI: The role of Pyk2 and c-Cbl.
AB  - Phosphatidylinositol 3-kinasebeta (PI3Kbeta) plays a predominant role in integrin
      outside-in signaling and in platelet activation by GPVI engagement. We have shown
      that the tyrosine kinase Pyk2 mediates PI3Kbeta activation downstream of integrin
      alphaIIbbeta3, and promotes the phosphorylation of the PI3K-associated adaptor
      protein c-Cbl. In this study, we compared the functional correlation between Pyk2
      and PI3Kbeta upon recruitment of the two main platelet collagen receptors,
      integrin alpha2beta1 and GPVI. PI3Kbeta-mediated phosphorylation of Akt was
      inhibited in Pyk2-deficient platelets adherent to monomeric collagen through
      integrin alpha2beta1, but occurred normally upon GPVI ligation. Integrin
      alpha2beta1 engagement led to Pyk2-independent association of c-Cbl with PI3K.
      However, c-Cbl was not phosphorylated in adherent platelets, and phosphorylation
      of Akt occurred normally in c-Cbl-deficient platelets, indicating that the c-Cbl
      is dispensable for Pyk2-mediated PI3Kbeta activation. Stimulation of platelets
      with CRP, a selective GPVI ligand, induced c-Cbl phosphorylation in the absence
      of Pyk2, but failed to promote its association with PI3K. Pyk2 activation was
      completely abrogated in PI3KbetaKD, but not in PI3KgammaKD platelets, and was
      strongly inhibited by Src kinases and phospholipase C inhibitors, and by BAPTA
      AM. The absence of PI3Kbeta activity also hampered GPVI-induced tyrosine
      phosphorylation and activation of PLCgamma2, preventing intracellular Ca2+
      increase and phosphorylation of pleckstrin. Moreover, GPVI-induced intracellular
      Ca2+ increase and pleckstrin phosphorylation were also strongly inhibited in
      human platelets treated with the PI3Kbeta inhibitor TGX-221. These results
      outline important differences in the regulation of PI3Kbeta by GPVI and integrin
      alpha2beta1 and suggest that inhibition of Pyk2 may target PI3Kbeta activation in
      a selective context of platelet stimulation.

PMID- 25960398
TI  - Hyper-dependence of breast cancer cell types on the nuclear transporter Importin
      beta1.
AB  - We previously reported that overexpression of members of the Importin (Imp)
      superfamily of nuclear transporters results in increased nuclear trafficking
      through conventional transport pathways in tumour cells. Here we show for the
      first time that the extent of overexpression of Impbeta1 correlates with disease
      state in the MCF10 human breast tumour progression system. Excitingly, we find
      that targeting Impbeta1 activity through siRNA is >30 times more efficient in
      decreasing the viability of malignant ductal carcinoma cells compared to isogenic
      non-transformed counterparts, and is highly potent and tumour selective at
      subnanomolar concentrations. Tumour cell selectivity of the siRNA effects was
      unique to Impbeta1 and not other Imps, with flow cytometric analysis showing >60%
      increased cell death compared to controls concomitant with reduced nuclear import
      efficiency as indicated by confocal microscopic analysis. This hypersensitivity
      of malignant cell types to Impbeta1 knockdown raises the exciting possibility of
      anti-cancer therapies targeted at Impbeta1. 

PMID- 25960400
TI  - XIV International Symposium on Solid State Dosimetry - ISSSD 2014.

PMID- 25960399
TI  - Increased physical activity may be more protective for metabolic syndrome than
      reduced caloric intake. An analysis of estimated energy balance in U.S. adults:
      2007-2010 NHANES.
AB  - BACKGROUND AND AIM: The purpose of this study was to examine the association
      between physical activity (PA), caloric intake, and Metabolic Syndrome (MetS) in
      a representative sample of the United States population. METHODS AND RESULTS:
      Data for 4327 adults from 2007 to 2010 NHANES were analyzed. MetS was defined
      using both ATPIII and AHA/NHLBI criteria. Weekly moderate and vigorous physical
      activity (PA) minutes from work, leisure-time, and transportation PA were used to
      estimate Total Energy Expenditure (TEE) from Basal Metabolic Rate (BMR) using the
      Harris-Benedict equation. Average total calories (KCAL) from two 24-h dietary
      recalls were used to compare energy intake and expenditure between subjects with
      and without MetS. An alpha of 0.05 was used to determine statistical differences.
      The age adjusted prevalence of MetS was 21.9% (95% CI 20.1-23.6) and 36.8% (34.7
      39.0) using ATPIII and AHA/NHLBI criteria, respectively. The estimated population
      mean for KCAL/TEE was 0.83 (95% CI 0.82-0.84), and the mean for KCAL/BMR was 1.25
      (95% CI 1.23-1.27). Subjects without MetS (MetS-) reported 36 +/- 13 (ATPIII) and
      45 +/- 18 (AHA/NHLBI) more daily moderate PA minutes than subjects with MetS
      (MetS+). At each level of PA, MetS- consumed more calories relative to BMR and
      TEE than MetS+. For both normal and overweight adults, KCAL/BMR was higher for
      MetS- than MetS+. For all BMI groups, there were no differences between MetS- and
      MetS+ with respect to KCAL/TEE. Though MetS+ adults in either MetS criteria were
      generally less physically active, MetS- adults maintained a higher caloric intake
      relative to estimated energy needs. CONCLUSIONS: These results suggest energy
      needs may be distorted in Metabolic Syndrome and increased physical activity may
      be more protective than reduced caloric intake.

PMID- 25960401
TI  - Length of hospital stay and 30-day readmission following heart failure
      hospitalization: insights from the EVEREST trial.
AB  - AIMS: Previous reports have provided conflicting data regarding the relationship
      between length of stay (LOS) and subsequent readmission risk among patients
      hospitalized for heart failure (HF). METHODS AND RESULTS: We performed a post-hoc
      analysis of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study
      with Tolvaptan (EVEREST) trial to evaluate the differences in LOS overall and
      between geographic regions (North America, South America, Western Europe, and
      Eastern Europe) in association with all-cause and cause-specific [HF,
      cardiovascular (CV) non-HF, and non-CV] readmissions within 30 days of discharge
      after HF hospitalization. The present analysis included 4020 patients enrolled
      from 20 countries who were alive at discharge. Median [interquartile range (IQR)]
      LOS was 8 (4-11) days. The 30-day readmission rates were 15.7% [95% confidence
      interval (CI) 14.6-16.8] for all-cause; 5.6% (95% CI 4.9-6.3) for HF; 4.4% (95%
      CI 3.8-5.1) for CV non-HF; and 5.8% (95% CI 5.1-6.6) for non-CV readmissions.
      There was a positive correlation between LOS and all-cause readmissions (r =
      0.09, 95% CI 0.06-0.12). The adjusted odds ratio for the top (>=14 days) vs. the
      bottom (<=3 days) quintile for LOS was 1.39 (95% CI 0. 92-2.11) for all-cause
      readmissions, 0.43 (95% CI 0.24-0.79) for HF, 2.99 (95% CI 1.49-6.02) for CV non
      HF, and 1.72 (95% CI 1.05-2.81) for non-CV readmissions. With the exception of
      Western Europe, these findings remained largely consistent across geographic
      regions. CONCLUSION: In this large multinational cohort of hospitalized HF
      patients, longer LOS was associated with a higher risk for all-cause, CV non-HF,
      and non-CV readmissions, but a lower risk of HF readmissions within 30 days of
      discharge. These results may inform strategies to reduce readmissions.

PMID- 25960402
TI  - Comparative technoeconomic analysis of a softwood ethanol process featuring
      posthydrolysis sugars concentration operations and continuous fermentation with
      cell recycle.
AB  - Economical production of second generation ethanol from Ponderosa pine is of
      interest due to widespread mountain pine beetle infestation in the western United
      States and Canada. The conversion process is limited by low glucose and high
      inhibitor concentrations resulting from conventional low-solids dilute acid
      pretreatment and enzymatic hydrolysis. Inhibited fermentations require larger
      fermentors (due to reduced volumetric productivity) and low sugars lead to low
      ethanol titers, increasing distillation costs. In this work, multiple effect
      evaporation (MEE) and nanofiltration (NF) were evaluated to concentrate the
      hydrolysate from 30 g/l to 100, 150, or 200 g/l glucose. To ferment this high
      gravity, inhibitor containing stream, traditional batch fermentation was compared
      with continuous stirred tank fermentation (CSTF) and continuous fermentation with
      cell recycle (CSTF-CR). Equivalent annual operating cost (EAOC = amortized
      capital + yearly operating expenses) was used to compare these potential
      improvements for a local-scale 5 MGY ethanol production facility. Hydrolysate
      concentration via evaporation increased EAOC over the base process due to the
      capital and energy intensive nature of evaporating a very dilute sugar stream;
      however, concentration via NF decreased EAOC for several of the cases (by 2 to
      15%). NF concentration to 100 g/l glucose with a CSTF-CR was the most economical
      option, reducing EAOC by $0.15 per gallon ethanol produced. Sensitivity analyses
      on NF options showed that EAOC improvement over the base case could still be
      realized for even higher solids removal requirements (up to two times higher
      centrifuge requirement for the best case) or decreased NF performance.

PMID- 25960403
TI  - Effects of hybrid cycle and handcycle exercise on cardiovascular disease risk
      factors in people with spinal cord injury: A randomized controlled trial.
AB  - OBJECTIVE: To examine the effects of a 16-week exercise programme, using either a
      hybrid cycle or a handcycle, on cardiovascular disease risk factors in people
      with spinal cord injury. PARTICIPANTS: Nineteen individuals with spinal cord
      injury >= 8 years. DESIGN: Multicentre randomized controlled trial. Both the
      hybrid cycle group (n = 9) and the handcycle group (n = 10) trained twice a week
      for 16 weeks on the specific cycle. Outcome measures obtained pre and post the
      programme were: metabolic syndrome components (waist circumference, systolic and
      diastolic blood pressure, high-density lipoprotein cholesterol, triglycerides and
      insulin resistance), inflammatory status (C-reactive protein (CRP), interleukin
      (IL)-6 and -10), and visceral adiposity (trunk and android fat). RESULTS: For all
      outcome measures, there were no significant differences over time between the 2
      training groups. Overall significant reductions were found for waist
      circumference (p = 0.001), diastolic blood pressure (p = 0.03), insulin
      resistance (p = 0.006), CRP (p = 0.05), IL-6 (p = 0.04), IL-6/IL-10 ratio (p =
      0.03), and trunk (p = 0.04) and android (p = 0.02) fat percentage. No significant
      main effects for time were observed for systolic blood pressure, triglycerides,
      high-density lipoprotein cholesterol, IL-10, and trunk and android fat mass.
      CONCLUSION: The 16-week exercise programme, using either a hybrid cycle or a
      handcycle, found similar beneficial effects on metabolic syndrome components,
      inflammatory status and visceral adiposity, indicating that there were no
      additional benefits of functional electrical stimulation-induced leg exercise
      over handcycle exercise alone.

PMID- 25960404
TI  - A new surgical technique for hymenoplasty: A solution, but for which problem?

PMID- 25960405
TI  - Conformational Changes Underlying Desensitization of the Pentameric Ligand-Gated
      Ion Channel ELIC.
AB  - Structural rearrangements underlying functional transitions of pentameric ligand
      gated ion channels (pLGICs) are not fully understood. Using (19)F nuclear
      magnetic resonance and electron spin resonance spectroscopy, we found that ELIC,
      a pLGIC from Erwinia chrysanthemi, expanded the extracellular end and contracted
      the intracellular end of its pore during transition from the resting to an
      apparent desensitized state. Importantly, the contraction at the intracellular
      end of the pore likely forms a gate to restrict ion transport in the desensitized
      state. This gate differs from the hydrophobic gate present in the resting state.
      Conformational changes of the TM2-TM3 loop were limited to the N-terminal end.
      The TM4 helices and the TM3-TM4 loop appeared relatively insensitive to agonist
      mediated structural rearrangement. These results indicate that conformational
      changes accompanying functional transitions are not uniform among different ELIC
      regions. This work also revealed the co-existence of multiple conformations for a
      given state and suggested asymmetric conformational arrangements in a homomeric
      pLGIC. 

PMID- 25960406
TI  - The Elp2 subunit is essential for elongator complex assembly and functional
      regulation.
AB  - Elongator is a highly conserved multiprotein complex composed of six subunits
      (Elp1-6). Elongator has been associated with various cellular activities and has
      attracted clinical attention because of its role in certain neurodegenerative
      diseases. Here, we present the crystal structure of the Elp2 subunit revealing
      two seven-bladed WD40 beta propellers, and show by structure-guided mutational
      analyses that the WD40 fold integrity of Elp2 is necessary for its binding to
      Elp1 and Elp3 subunits in multiple species. The detailed biochemical experiments
      indicate that Elp2 binds microtubules through its conserved alkaline residues in
      vitro and in vivo. We find that both the mutually independent Elp2-mediated
      Elongator assembly and the cytoskeleton association are important for yeast
      viability. In addition, mutation of Elp2 greatly affects the histone H3
      acetylation activity of Elongator in vivo. Our results indicate that Elp2 is a
      necessary component for functional Elongator and acts as a hub in the formation
      of various complexes. 

PMID- 25960407
TI  - The origin of consistent protein structure refinement from structural averaging.
AB  - Recent studies have shown that explicit solvent molecular dynamics (MD)
      simulation followed by structural averaging can consistently improve protein
      structure models. We find that improvement upon averaging is not limited to
      explicit water MD simulation, as consistent improvements are also observed for
      more efficient implicit solvent MD or Monte Carlo minimization simulations. To
      determine the origin of these improvements, we examine the changes in model
      accuracy brought about by averaging at the individual residue level. We find that
      the improvement in model quality from averaging results from the superposition of
      two effects: a dampening of deviations from the correct structure in the least
      well modeled regions, and a reinforcement of consistent movements towards the
      correct structure in better modeled regions. These observations are consistent
      with an energy landscape model in which the magnitude of the energy gradient
      toward the native structure decreases with increasing distance from the native
      state. 

PMID- 25960408
TI  - Interactions by the Fungal Flo11 Adhesin Depend on a Fibronectin Type III-like
      Adhesin Domain Girdled by Aromatic Bands.
AB  - Saccharomyces cerevisiae harbors a family of GPI-anchored cell wall proteins for
      interaction with its environment. The flocculin Flo11, a major representative of
      these fungal adhesins, confers formation of different types of multicellular
      structures such as biofilms, flors, or filaments. To understand these environment
      dependent growth phenotypes on a molecular level, we solved the crystal structure
      of the N-terminal Flo11A domain at 0.89-A resolution. Besides a hydrophobic
      apical region, the Flo11A domain consists of a beta sandwich of the fibronectin
      type III domain (FN3). We further show that homophilic Flo11-Flo11 interactions
      and heterophilic Flo11-plastic interactions solely depend on the Flo11A domain
      and are strongly pH dependent. These functions of Flo11A involve an apical region
      with its surface-exposed aromatic band, which is accompanied by acidic stretches.
      Together with electron microscopic reconstructions of yeast cell-cell contact
      sites, our data suggest that Flo11 acts as a spacer-like, pH-sensitive adhesin
      that resembles a membrane-tethered hydrophobin. 

PMID- 25960409
TI  - Molecular Basis of the Activity and the Regulation of the Eukaryotic-like S/T
      Protein Kinase PknG from Mycobacterium tuberculosis.
AB  - Tuberculosis remains one of the world's deadliest human diseases, with a high
      prevalence of antibiotic-resistant Mycobacterium tuberculosis (Mtb) strains. A
      molecular understanding of processes underlying regulation and adaptation of
      bacterial physiology may provide novel avenues for the development of antibiotics
      with unconventional modes of action. Here, we focus on the multidomain S/T
      protein kinase PknG, a soluble enzyme that controls central metabolism in
      Actinobacteria and has been linked to Mtb infectivity. Our biochemical and
      structural studies reveal how different motifs and domains flanking the catalytic
      core regulate substrate selectivity without significantly affecting the intrinsic
      kinase activity, whereas a rubredoxin-like domain is shown to downregulate
      catalysis through specific intramolecular interactions that modulate access to a
      profound substrate-binding site. Our findings provide the basis for the selective
      and specific inhibition of PknG, and open new questions about regulation of
      related bacterial and eukaryotic protein kinases. 

PMID- 25960411
TI  - Heterogeneity in D'Amico classification-based low-risk prostate cancer:
      Differences in upgrading and upstaging according to active surveillance
      eligibility.
AB  - BACKGROUND: To date, no study has examined clinical, pathological, and surgical
      characteristics of D'Amico low-risk patients according to active surveillance
      (AS) eligibility. MATERIAL AND METHODS: We relied on patients with low-risk
      prostate cancer, who were classified based on the D'Amico classification, treated
      with radical prostatectomy (RP) between 2008 and 2013 at the Martini-Clinic
      Prostate Cancer Center. We assessed differences in clinical, pathological, and
      surgical characteristics in D'Amico low-risk patients according to AS eligibility
      (prostate-specific antigen [PSA]<= 10 ng/ml, Gleason score <= 3 + 3, <= 2
      positive cores,<=5 0% tumor content per core, and <= cT1-2a). Multivariable
      logistic regression analyses targeted 2 end points: (1) presence of either
      intermediate- or high-risk characteristics (Gleason score >= 3+4 or >= pT3 or
      pN1) or (2) exclusive presence of high-risk characteristics (Gleason score >= 4+4
      or >= pT3 or pN1) at RP. RESULTS: Of 1,331 patients low-risk prostate cancer
      classified based on the D'Amico classification, 825 (62%) men were eligible for
      AS. AS candidates were less frequently either upgraded (55% vs. 78%, P<0.001) or
      upstaged (8% vs. 15%, P<0.001). Similarly, at final pathology, AS candidates less
      frequently harbored either intermediate- or high-risk (56% vs. 78%, P<0.001), or
      exclusive high-risk characteristics (9% vs. 16%, P<0.001). Tumor involvement per
      core (>50%) (most powerful), number of positive cores, PSA values, and age were
      independent predictors for either intermediate- or high-risk characteristics at
      RP. Tumor involvement per core and PSA values were independent predictors for
      exclusive high-risk characteristics at RP. CONCLUSIONS: D'Amico low-risk patients
      did not have a homogeneous histology at RP. Especially, non-AS candidates were at
      a higher risk of either upgrading or upstaging at final pathology. Tumor
      involvement greater than 50% per core was the most powerful indicator of adverse
      pathology. Therefore, D'Amico low-risk criteria are not safe enough to identify
      AS candidates.

PMID- 25960410
TI  - Structural Basis for Multi-specificity of MRG Domains.
AB  - Chromatin-binding proteins play vital roles in the assembly and recruitment of
      multi-subunit complexes harboring effector proteins to specific genomic loci.
      MRG15, a chromodomain-containing chromatin-binding protein, recruits diverse
      chromatin-associated complexes that regulate gene transcription, DNA repair, and
      RNA splicing. Previous studies with Pf1, another chromatin-binding subunit of the
      Sin3S/Rpd3S histone deacetylase complex, defined the sequence and structural
      requirements for interactions with the MRG15 MRG domain, a common target of
      diverse subunits in the aforementioned complexes. We now show that MRGBP, a
      member of the Tip60/NuA4 histone acetyltransferase complex, engages the same two
      surfaces of the MRG domain as Pf1. High-affinity interactions occur via a
      bipartite structural motif including an FxLP sequence motif. MRGBP shares little
      sequence and structural similarity with Pf1, yet targets similar pockets on the
      surface of the MRG domain, mimicking Pf1 in its interactions. Our studies shed
      light onto how MRG domains have evolved to bind diverse targets. 

PMID- 25960413
TI  - Structure of the secretory cells of male and female adult guinea pigs Harderian
      gland.
AB  - The main objective of this study was to investigate the structure of the
      Harderian gland (HG) in male and female guinea pigs. A total number of sixteen
      animals of 4 months age were divided according to sex into two groups; eight
      animals each. Unfixed glands were weighed and their length and width were
      measured. Specimens from fixed glands were processed and examined using light,
      transmission electron microscopy and immunohistochemistry for the detection of
      the presence of chromogranin A (CgA). The gland consisted of a well-developed
      duct system which included both intra and extra parenchymal ducts and secretory
      end pieces lined by many types of cells of variable morphological features and
      modes of secretion. However, the holocrine mode of secretion was rare as mitotic
      figures were occasionally present. The interstitial cells included fibroblasts
      and immune cells (mast cells, lymphocyte, plasma cells and macrophages). The
      secretion produced by the gland included lipid, protein, neutral mucin and CgA
      which may be a newly identified constituent of biologically potent proteins
      stored in the cells of the guinea pig HG. Neutral mucin and CgA may function in
      photoprotection. The gland revealed sexual dimorphism in mast cells and blood
      capillaries number and chromogranin secretory activity. 

PMID- 25960412
TI  - Genetic variations in genes involved in testosterone metabolism are associated
      with prostate cancer progression: A Spanish multicenter study.
AB  - BACKGROUND: Prostate cancer (PCa) is an androgen-dependent disease. Nonetheless,
      the role of single nucleotide polymorphisms (SNPs) in genes encoding androgen
      metabolism remains an unexplored area. PURPOSE: To investigate the role of
      germline variations in cytochrome P450 17A1 (CYP17A1) and steroid-5alpha
      reductase, alpha-polypeptides 1 and 2 (SRD5A1 and SRD5A2) genes in PCa. PATIENTS
      AND METHODS: In total, 494 consecutive Spanish patients diagnosed with
      nonmetastatic localized PCa were included in this multicenter study and were
      genotyped for 32 SNPs in SRD5A1, SRD5A2, and CYP17A1 genes using a Biotrove
      OpenArray NT Cycler. Clinical data were available. Genotypic and allelic
      frequencies, as well as haplotype analyses, were determined using the web-based
      environment SNPator. All additional statistical analyses comparing clinical data
      and SNPs were performed using PASW Statistics 15. RESULTS: The call rate obtained
      (determined as the percentage of successful determinations) was 97.3% of
      detection. A total of 2 SNPs in SRD5A1-rs3822430 and rs1691053-were associated
      with prostate-specific antigen level at diagnosis. Moreover, G carriers for both
      SNPs were at higher risk of presenting initial prostate-specific antigen
      levels>20ng/ml (Exp(B) = 2.812, 95% CI: 1.397-5.657, P = 0.004) than those who
      are AA-AA carriers. Haplotype analyses showed that patients with PCa
      nonhomozygous for the haplotype GCTTGTAGTA were at an elevated risk of presenting
      bigger clinical tumor size (Exp(B) = 3.823, 95% CI: 1.280-11.416, P = 0.016), and
      higher Gleason score (Exp(B) = 2.808, 95% CI: 1.134-6.953, P = 0.026).
      CONCLUSIONS: SNPs in SRD5A1 seem to affect the clinical characteristics of
      Spanish patients with PCa.

PMID- 25960415
TI  - The etiology of lenticulostriate vasculopathy and the role of congenital
      infections.
AB  - Lenticulostriate vasculopathy (LSV) refers to increased echogenicity of the
      penetrating vessels that supply the basal ganglia and segments of the internal
      capsule seen on cranial ultrasound. Initially identified in infants with
      congenital infection, LSV has now been associated with a variety of infectious
      and non-infectious conditions. Although robust epidemiologic studies are lacking,
      the available evidence does not support broad evaluation for multiple congenital
      infections when LSV is identified. We propose screening infants with LSV for
      congenital cytomegalovirus infection and ensuring that prenatal screening
      included appropriate testing for syphilis, human immunodeficiency virus, and
      rubella-immune status. Large, prospective observational studies are needed to
      determine the incidence of LSV and the relative contribution of infectious and
      non-infectious conditions to LSV in the neonate. 

PMID- 25960416
TI  - Optimizing a parametrized Thomas-Fermi-Dirac-Weizsacker density functional for
      atoms.
AB  - Because of issues with accuracy and transferability of existing orbital-free (OF)
      density functionals, OF functional development remains an active research area.
      However, due to numerical difficulties, all-electron self-consistent assessment
      of OF functionals is limited. Using an all-electron radial OFDFT code, we
      evaluate the performance of a parametrized OF functional for a wide range in
      parameter space. Specifically, we combine the parametrized Thomas-Fermi
      Weizsacker kinetic model (lambda and gamma for the fractions of Weizsacker and
      Thomas-Fermi functionals, respectively) with a local density approximation (LDA)
      for the exchange-correlation functional. In order to obtain the converged results
      for lambda values other than lambda = 1, we use the potential scaling introduced
      in previous work. Because we work within a wide region in parameter space, this
      strategy provides an effective route towards better understanding of the
      parameter interplay that allows us to achieve good agreement with the Kohn-Sham
      (KS) model. Here, our interest lies in total energy, Euler equation eigenvalue,
      and electronic densities when the parameters are varied between 0.2 and 1.5. We
      observe that a one-to-one relation between lambda and gamma defines a region in
      parameter space that allows the atomic energies to be approximated with a very
      small average error (less than 3% percent for all the atoms studied) with respect
      to the KS reference energies. For each atom, the reference KS HOMO eigenvalue can
      also be reproduced with a similar error, but the one-to-one correspondence
      between lambda and gamma belongs to a different region of the same parameter
      space. Contrary to both properties, the atomic density behaves more smoothly and
      the error in reproducing the KS reference densities appears more insensitive to
      variation of the parameters (with mostly an average integrated difference of 0.15
      0.20 |e| per electron). These results pave the way towards testing of parameter
      transferability and further systematic improvement of OF density functionals. 

PMID- 25960414
TI  - Commissural axonal corridors instruct neuronal migration in the mouse spinal
      cord.
AB  - Unravelling how neurons are guided during vertebrate embryonic development has
      wide implications for understanding the assembly of the nervous system. During
      embryogenesis, migration of neuronal cell bodies and axons occurs simultaneously,
      but to what degree they influence each other's development remains obscure. We
      show here that within the mouse embryonic spinal cord, commissural axons bisect,
      delimit or preconfigure ventral interneuron cell body position. Furthermore,
      genetic disruption of commissural axons results in abnormal ventral interneuron
      cell body positioning. These data suggest that commissural axonal fascicles
      instruct cell body position by acting either as border landmarks (axon-restricted
      migration), which to our knowledge has not been previously addressed, or acting
      as cellular guides. This study in the developing spinal cord highlights an
      important function for the interaction of cell bodies and axons, and provides a
      conceptual proof of principle that is likely to have overarching implications for
      the development of neuronal architecture. 

PMID- 25960417
TI  - 1064-nm Nd: YAG laser-assisted cartilage reshaping for treating ear protrusions.
AB  - BACKGROUND: Correction of prominent ears is a common plastic surgical procedure.
      The laser-assisted cartilage reshaping (LACR) technique for protruding ears was
      developed at the French National Institute of Health and Medical Research in
      Lille, France, using both the 1064- and 1540-nm wavelengths, with a view to
      simplifying the surgical procedure. Herein we report our results with the 1064-nm
      wavelength. METHODS: Between 2008 and 2010, twenty-six 1064-nm LACR procedures in
      14 patients were performed. Twelve patients received treatment to both ears, and
      2 patients received treatment to one ear. Each procedure consisted of a single
      treatment session. The treatment consisted of laser irradiation of both sides of
      the helix with single pulses of 70 J/cm2. The beam diameter was 6 mm. Early and
      late complications were defined and reviewed for all patients. Satisfaction was
      assessed by patients using a visual analogue scale from 0 (unsatisfied) to 20
      (highly satisfied). The superior and middle cephaloauricular distances were
      prospectively evaluated at 6 months after treatment. RESULTS: Complications
      included eight cases of localized skin burns and one case of dermatitis. The mean
      right/left superior and middle cephaloauricular distances were 10.5+/-1.5
      mm/10.7+/-1.0 mm and 16.3+/-2.2 mm/16.3+/-2.8 mm, respectively, as compared to
      17.5+/-2.9 mm/18.6+/-2.5 mm (P<0.01) and 24.5+/-2.6 mm/24.7+/-1.7 mm (P<0.01)
      before the operation. Mean patient satisfaction was 16.8/20+/-3.3. CONCLUSION:
      Despite promising results for cartilage reshaping, the 1064-nm LACR procedure
      often leads to skin burns and inflammatory tissue reaction after treatment.
      Moreover, LACR with the 1064-nm wavelength is painful and necessitates local
      anaesthesia. LEVEL OF EVIDENCE: 4.

PMID- 25960418
TI  - Medicare Managed Care Spillovers and Treatment Intensity.
AB  - Evidence suggests that the share of Medicare managed care enrollees in a region
      affects the costs of treating traditional fee-for-service (FFS) Medicare
      beneficiaries; however, little is known about the mechanisms through which these
      'spillover effects' operate. This paper examines the relationship between
      Medicare managed care penetration and treatment intensity for FFS enrollees
      hospitalized with a primary diagnosis of AMI. I find that increased Medicare
      managed care penetration is associated with a reduction in both the costs and the
      treatment intensity of FFS AMI patients. Specifically, as Medicare managed care
      penetration increases, FFS AMI patients are less likely to receive surgical
      reperfusion and mechanical ventilation and to experience an overall reduction in
      the number of inpatient procedures. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 25960420
TI  - The extracellular matrix and transforming growth factor-beta1: Tale of a strained
      relationship.
AB  - Physiological tissue repair aims at restoring the mechano-protective properties
      of the extracellular matrix. Consequently, redundant regulatory mechanisms are in
      place ensuring that tissue remodeling terminates once matrix homeostasis is re
      established. If these mechanisms fail, stromal cells become continuously
      activated, accumulate excessive amounts of stiff matrix, and fibrosis develops.
      In this mini-review, I develop the hypothesis that the mechanical state of the
      extracellular matrix and the pro-fibrotic transforming growth factor (TGF)-beta1
      cooperate to regulate the remodeling activities of stromal cells. TGF-beta1 is
      stored in the matrix as part of a large latent complex and can be activated by
      cell contractile force that is transmitted by integrins. Matrix straining and
      stiffening lower the threshold for TGF-beta1 activation by increasing the
      mechanical resistance to cell pulling. Different elements of this mechanism can
      be pharmacologically targeted to interrupt the mechanical positive feedback loop
      of fibrosis, including specific integrins and matrix protein interactions. 

PMID- 25960419
TI  - Latent TGF-beta-binding proteins.
AB  - The LTBPs (or latent transforming growth factor beta binding proteins) are
      important components of the extracellular matrix (ECM) that interact with
      fibrillin microfibrils and have a number of different roles in microfibril
      biology. There are four LTBPs isoforms in the human genome (LTBP-1, -2, -3, and 
      4), all of which appear to associate with fibrillin and the biology of each
      isoform is reviewed here. The LTBPs were first identified as forming latent
      complexes with TGFbeta by covalently binding the TGFbeta propeptide (LAP) via
      disulfide bonds in the endoplasmic reticulum. LAP in turn is cleaved from the
      mature TGFbeta precursor in the trans-golgi network but LAP and TGFbeta remain
      strongly bound through non-covalent interactions. LAP, TGFbeta, and LTBP together
      form the large latent complex (LLC). LTBPs were originally thought to primarily
      play a role in maintaining TGFbeta latency and targeting the latent growth factor
      to the extracellular matrix (ECM), but it has also been shown that LTBP-1
      participates in TGFbeta activation by integrins and may also regulate activation
      by proteases and other factors. LTBP-3 appears to have a role in skeletal
      formation including tooth development. As well as having important functions in
      TGFbeta regulation, TGFbeta-independent activities have recently been identified
      for LTBP-2 and LTBP-4 in stabilizing microfibril bundles and regulating elastic
      fiber assembly. 

PMID- 25960421
TI  - Testing domain-general theories of perceptual awareness with auditory brain
      responses.
AB  - Past research has identified several candidate neural correlates of consciousness
      (NCCs) during visual perception. Recent research on auditory perception shows
      promise for establishing the generality of various NCCs across sensory
      modalities, as well as for revealing differences in how conscious processing
      unfolds in different sensory systems. 

PMID- 25960422
TI  - Do drivers with epilepsy have higher rates of motor vehicle accidents than those
      without epilepsy?
AB  - OBJECTIVE: We sought to understand the magnitude of the risk that drivers with
      epilepsy (DWE) contribute to motor vehicle accidents (MVAs) compared to other
      drivers. METHODS: We performed an evidence-based, systematic review using the
      American Academy of Neurology (AAN) guideline methodology. RESULTS: Contributory
      evidence consisted of six Class II studies and one Class III study. Two articles
      reported a trend toward a decreased rate of overall MVA rates for DWE when
      compared with the general population with a relative risk (RR) of 0.86 (95% CI:
      0.65-1.14) (Class III) and a RR of 1.00 (95% CI: 0.95-1.06) (Class II); both
      studies used patient report to ascertain MVA rates. Three Class II studies
      reported either a trend toward or an increased risk of MVA rates for DWE when
      compared with the general population with a RR of 1.62 (95% confidence interval
      (CI): 0.95-2.76), as ascertained by insurance, emergency department, and
      physician reporting databases, a RR of 1.73 (95% CI 1.58-1.90), as ascertained by
      police reports, and a RR of 7.01 (95% CI 2.18-26.13), as ascertained by casualty
      department visits. One Class II study showed that, compared to fatal crashes with
      DWE, fatal crashes were 26 times more likely to occur because of other medical
      conditions and 156 times more likely to occur because of alcohol abuse. Motor
      vehicle accident crashes due to seizures in DWE occurred in one out of every 2800
      MVAs, as reported in another Class II study. CONCLUSIONS: The evidence for the
      difference in MVA rates in DWE compared to the general population is
      inconsistent, and no conclusion can be made. Important methodological differences
      across the studies contribute to the imprecision. Future research should be
      performed using objective measures rather than self-reporting of MVAs by DWE and
      "miles driven" as the denominator to calculate MVA rates.

PMID- 25960424
TI  - The dilemma of adult-onset Rasmussen encephalitis clinical assessment: Proposal
      for a new bedside tool to evaluate disease progression.

PMID- 25960423
TI  - Use of the EpiNet database for observational study of status epilepticus in
      Auckland, New Zealand.
AB  - The EpiNet project has been established to facilitate investigator-initiated
      clinical research in epilepsy, to undertake epidemiological studies, and to
      simultaneously improve the care of patients who have records created within the
      EpiNet database. The EpiNet database has recently been adapted to collect
      detailed information regarding status epilepticus. An incidence study is now
      underway in Auckland, New Zealand in which the incidence of status epilepticus in
      the greater Auckland area (population: 1.5 million) will be calculated. The form
      that has been developed for this study can be used in the future to collect
      information for randomized controlled trials in status epilepticus. This article
      is part of a Special Issue entitled "Status Epilepticus". 

PMID- 25960425
TI  - Comparison of the effectiveness of four antiepileptic drugs in the treatment of
      status epilepticus according to four different efficacy criteria.
AB  - The preliminary data presented here shall give an impression on how different
      criteria for the identification of an antiepileptic drug (AED) with a possible or
      certain treatment effect can have an influence on the results of retrospective
      case series. We present a data subset from a large retrospective study which,
      when completed, will cover all treatment episodes of status epilepticus (SE) at
      the neurological department of the Universitatsmedizin Rostock from January 2010
      to June 2013. We compare and contrast the results of four different efficacy
      criteria for the effectiveness of phenytoin (PHT), valproate (VPA), levetiracetam
      (LEV), and lacosamide (LCM): criterion 1 = the last AED administered before SE
      termination; criterion 2 = the last drug introduced into the antiepileptic
      therapy within 72 h before SE termination and without changes in the
      comedication; criterion 3 = the last drug introduced into the antiepileptic
      therapy or increased in dose within 24h before SE termination without changes in
      the comedication; and criterion 4 = the last drug introduced into the
      antiepileptic therapy within 72 h before SE termination, even allowing changes in
      the comedication. Thirty-seven treatment episodes in 32 patients (13 male and 19
      female, mean age at first episode: 68 years, SD: 17) could be analyzed. In 31
      episodes, at least one AED was given intravenously. Efficacy rates in the whole
      case series according to all four criteria were not significantly different
      between the four AEDs, but there was a considerable difference in the efficacy
      rates of each AED when evaluating them with the different efficacy criteria. Our
      data show that statistically significant results concerning the efficacy of
      different AEDs in different subtypes of SE may depend on the outcome criteria.
      Therefore, efficacy criteria for the effectiveness of AEDs in the treatment of SE
      should be standardized. This article is part of a Special Issue entitled Status
      Epilepticus.

PMID- 25960426
TI  - Spot peptide arrays and SPR measurements: throughput and quantification in
      antibody selectivity studies.
AB  - Antibody selectivity represents a major issue in the development of efficient
      immuno-therapeutics and detection assays. Its description requires a comparison
      of the affinities of the antibody for a significant number of antigen variants.
      In the case of peptide antigens, this task can now be addressed to a significant
      level of details owing to improvements in spot peptide array technologies. They
      allow the high-throughput mutational analysis of peptides with, depending on
      assay design, an evaluation of binding stabilities. Here, we examine the cross
      reactive capacity of an antibody fragment using the PEPperCHIP((r)) technology
      platform (PEPperPRINT GmbH, Heidelberg, Germany; >8800 peptides per microarray)
      combined with the surface plasmon resonance characterization (Biacore((r))
      technology; GE-Healthcare Biacore, Uppsala, Sweden) of a subset of interactions.
      ScFv1F4 recognizes the N-terminal end of oncoprotein E6 of human papilloma virus
      16. The spot permutation analysis (i.e. each position substituted by all amino
      acids except cysteine) of the wild type decapeptide (sequence (6)TAMFQDPQER(15))
      and of 15 variants thereof defined the optimal epitope and provided a ranking for
      variant recognition. The SPR affinity measurements mostly validated the ranking
      of complex stabilities deduced from array data and defined the sensitivity of
      spot fluorescence intensities, bringing further insight into the conditions for
      cross-reactivity. Our data demonstrate the importance of throughput and
      quantification in the assessment of antibody selectivity.

PMID- 25960427
TI  - Regular aspirin use and nasopharyngeal cancer risk: A case-control study in
      Italy.
AB  - Regular aspirin use has been associated to decreased risk of several cancers, but
      evidence on nasopharyngeal carcinoma is scanty. We conducted a hospital-based
      case-control study in Italy, enrolling 198 Caucasian patients with nasopharyngeal
      carcinoma. Controls were 592 cancer-free Caucasian patients admitted to the same
      catchment areas as cases; controls were frequency matched according to sex, age,
      and area of residence. Regular aspirin use was defined as taking at least one
      aspirin a week for at least 6 months. Three cases (1.5%) and 27 controls (4.5%)
      reported regular aspirin use (odds ratio=0.24; 95% CI: 0.07-0.87). The median
      duration of consumption was 15 months among cases and 60 months among controls.
      Although study findings should be considered with caution due to limited sample
      size, they provide further evidence on the protective effect of aspirin use in
      head and neck cancers. 

PMID- 25960428
TI  - Application of quasi-steady state methods to molecular motor transport on
      microtubules in fungal hyphae.
AB  - We consider bidirectional transport of cargo by molecular motors dynein and
      kinesin that walk along microtubules, and/or diffuse in the cell. The motors
      compete to transport cargo in opposite directions with respect to microtubule
      polarity (towards the plus or minus end of the microtubule). In recent work, Gou
      et al. (2014) used a hierarchical set of models, each consisting of continuum
      transport equations to track the evolution of motors and their cargo (early
      endosomes) in the specific case of the fungus Ustilago maydis. We complement
      their work using a framework of quasi-steady state analysis developed by Newby
      and Bressloff (2010) and Bressloff and Newby (2013) to reduce the models to an
      approximating steady state Fokker-Plank equation. This analysis allows us to find
      analytic approximations to the steady state solutions in many cases where the
      full models are not easily solved. Consequently, we can make predictions about
      parameter dependence of the resulting spatial distributions. We also characterize
      the overall rates of bulk transport and diffusion, and how these are related to
      state transition parameters, motor speeds, microtubule polarity distribution, and
      specific assumptions made. 

PMID- 25960429
TI  - Mitochondria-targeted hydrogen sulfide donor AP39 improves neurological outcomes
      after cardiac arrest in mice.
AB  - AIMS: Mitochondria-targeted hydrogen sulfide donor AP39, [(10-oxo-10-(4-(3-thioxo
      3H-1,2-dithiol-5yl)phenoxy)decyl) triphenylphosphonium bromide], exhibits
      cytoprotective effects against oxidative stress in vitro. We examined whether or
      not AP39 improves the neurological function and long term survival in mice
      subjected to cardiac arrest (CA) and cardiopulmonary resuscitation (CPR).
      METHODS: Adult C57BL/6 male mice were subjected to 8 min of CA and subsequent
      CPR. We examined the effects of AP39 (10, 100, 1000 nmol kg(-1)) or vehicle
      administered intravenously at 2 min before CPR (Experiment 1). Systemic oxidative
      stress levels, mitochondrial permeability transition, and histological brain
      injury were assessed. We also examined the effects of AP39 (10, 1000 nmol kg(-1))
      or vehicle administered intravenously at 1 min after return of spontaneous
      circulation (ROSC) (Experiment 2). ROSC was defined as the return of sinus rhythm
      with a mean arterial pressure >40 mm Hg lasting at least 10 seconds. RESULTS:
      Vehicle treated mice subjected to CA/CPR had poor neurological function and 10
      day survival rate (Experiment 1; 15%, Experiment 2; 23%). Administration of AP39
      (100 and 1000 nmol kg(-1)) 2 min before CPR significantly improved the
      neurological function and 10-day survival rate (54% and 62%, respectively) after
      CA/CPR. Administration of AP39 before CPR attenuated mitochondrial permeability
      transition pore opening, reactive oxygen species generation, and neuronal
      degeneration after CA/CPR. Administration of AP39 1 min after ROSC at 10 nmol kg(
      1), but not at 1000 nmol kg(-1), significantly improved the neurological function
      and 10-day survival rate (69%) after CA/CPR. CONCLUSION: The current results
      suggest that administration of mitochondria-targeted sulfide donor AP39 at the
      time of CPR or after ROSC improves the neurological function and long term
      survival rates after CA/CPR by maintaining mitochondrial integrity and reducing
      oxidative stress.

PMID- 25960431
TI  - Selection of reliable reference genes for gene expression studies in Clonostachys
      rosea 67-1 under sclerotial induction.
AB  - Reference genes are important to precisely quantify gene expression by real-time
      PCR. In order to identify stable and reliable expressed genes in mycoparasite
      Clonostachys rosea in different modes of nutrition, seven commonly used
      housekeeping genes, 18S rRNA, actin, beta-tubulin, elongation factor 1,
      ubiquitin, ubiquitin-conjugating enzyme and glyceraldehyde-3-phosphate
      dehydrogenase, from the effective biocontrol isolate C. rosea 67-1 were tested
      for their expression under sclerotial induction and during vegetative growth on
      PDA medium. Analysis by three software programs showed that differences existed
      among the candidates. Elongation factor 1 was most stable; the M value in geNorm,
      SD value in Bestkeeper and stability value in Normfinder analysis were 0.405,
      0.450 and 0.442, respectively, indicating that the gene elongation factor 1 could
      be used to normalize gene expression in C. rosea in both vegetative growth and
      parasitic process. By using elongation factor 1, the expression of a serine
      protease gene, sep, in different conditions was assessed, which was consistent
      with the transcriptomic data. This research provides an effective method to
      quantitate expression changes of target genes in C. rosea, and will assist in
      further investigation of parasitism-related genes of this fungus. 

PMID- 25960430
TI  - Saccharomyces cerevisiae: A novel and efficient biological control agent for
      Colletotrichum acutatum during pre-harvest.
AB  - In this study, we evaluated the efficiency of six isolates of Saccharomyces
      cerevisiae in controlling Colletotrichum acutatum, the causal agent of postbloom
      fruit drop that occur in pre-harvest citrus. We analyzed the mechanisms of action
      involved in biological control such as: production of antifungal compounds,
      nutrient competition, detection of killer activity, and production of hydrolytic
      enzymes of the isolates of S. cerevisiae on C. acutatum and their efficiency in
      controlling postbloom fruit drop on detached citrus flowers. Our results showed
      that all six S. cerevisiae isolates produced antifungal compounds, competed for
      nutrients, inhibited pathogen germination, and produced killer activity and
      hydrolytic enzymes when in contact with the fungus wall. The isolates were able
      to control the disease when detached flowers were artificially inoculated, both
      preventively and curatively. In this work we identified a novel potential
      biological control agent for C. acutatum during pre-harvest. This is the first
      report of yeast efficiency for the biocontrol of postbloom fruit drop, which
      represents an important contribution to the field of biocontrol of diseases
      affecting citrus populations worldwide. 

PMID- 25960432
TI  - A cultivation-independent PCR-RFLP assay targeting oprF gene for detection and
      identification of Pseudomonas spp. in samples from fibrocystic pediatric
      patients.
AB  - Species-specific genetic markers are crucial to develop faithful and sensitive
      molecular methods for the detection and identification of Pseudomonas aeruginosa
      (Pa). We have previously set up a PCR-RFLP protocol targeting oprF, the gene
      encoding the genus-specific outer membrane porin F, whose strong conservation and
      marked sequence diversity allowed detection and differentiation of environmental
      isolates (Agaras et al., 2012). Here, we evaluated the ability of the PCR-RFLP
      assay to genotype clinical isolates previously identified as Pa by conventional
      microbiological methods within a collection of 62 presumptive Pa isolates from
      different pediatric clinical samples and different sections of the Hospital de
      Ninos "Sor Maria Ludovica" from La Plata, Argentina. All isolates, but one, gave
      an oprF amplicon consistent with that from reference Pa strains. The sequence of
      the smaller-sized amplicon revealed that the isolate was in fact a mendocina
      Pseudomonas strain. The oprF RFLP pattern generated with TaqI or HaeIII nucleases
      matched those of reference Pa strains for 59 isolates (96%). The other two Pa
      isolates (4%) revealed a different RFLP pattern based on HaeIII digestion,
      although oprF sequencing confirmed that Pa identification was correct. We next
      tested the effectiveness of the PCR-RFLP to detect pseudomonads on clinical
      samples of pediatric fibrocystic patients directly without sample cultivation.
      The expected amplicon and its cognate RFLP profile were obtained for all samples
      in which Pa was previously detected by cultivation-dependent methods. Altogether,
      these results provide the basis for the application of the oprF PCR-RFLP protocol
      to directly detect and identify Pa and other non-Pa pseudomonads in fibrocystic
      clinical samples. 

PMID- 25960433
TI  - Fusion of hIgG1-Fc to 111In-anti-amyloid single domain antibody fragment VHH-pa2H
      prolongs blood residential time in APP/PS1 mice but does not increase brain
      uptake.
AB  - INTRODUCTION: Llama single domain antibody fragments (VHH), which can pass
      endothelial barriers, are being investigated for targeting amyloid plaque load in
      Alzheimer's disease (AD). Contrary to conventional human or murine antibodies
      consisting of IgG or F(ab')2 antibody fragments, VHH are able to effectively pass
      the blood brain barrier (BBB) in vitro. However, in earlier in vivo studies, anti
      amyloid VHH showed poor BBB passage due to their short serum half-lives. It would
      be of interest to develop a VHH based protein with elongated serum half-life to
      enhance BBB passage, allowing the VHH to more easily reach the cerebral amyloid
      deposits. METHODS: To increase serum persistence, the Fc portion of the human
      IgG1 antibody (hinge plus CH2 and CH3 domains) was fused to the C-terminus of the
      VHH (VHH-pa2H-Fc). To determine the pharmacokinetics and biodistribution profile
      of the fusion protein, the chelator p-SCN-Bz-DTPA was linked to the protein and
      thereafter labeled with radioactive indium-111 ((111)In). Double transgenic
      APPswe/PS1dE9 and wild type littermates were injected with 20 MUg VHH-pa2H-Fc
      DTPA-(111)In (10-20 MBq). Pharmacokinetics of the tracer was determined in blood
      samples at 10 intervals after injection and imaging using microSPECT was
      performed. The biodistribution of the radioactivity in various excised tissues
      was measured at 48 h after injection. RESULTS: We succeeded in the expression of
      the fusion protein VHH-pa2H-Fc in HEK293T cells with a yield of 50mg/L growth
      medium. The fusion protein showed homodimerization - necessary for successful Fc
      neonatal receptor recycling. Compared to VHH-pa2H, the Fc tailed protein retained
      high affinity for amyloid beta on human AD patient brain tissue sections, and
      significantly improved serum retention of the VHH. However, at 48 h after
      systemic injection of the non-fused VHH-DTPA-(111)In and the VHH-Fc-DTPA-(111)In
      fusion protein in transgenic mice, the specific brain uptake of VHH-Fc-DTPA
      (111)In was not improved compared to non-fused VHH-DTPA-(111)In. CONCLUSION:
      Using VHH-Fc conjugates increases the blood half-life of the protein. However,
      purely extending the time window for brain uptake does not increase BBB passage.
      Nevertheless, VHH-Fc holds promise for therapeutic applications where a sustained
      systemic circulation of VHH is advantageous.

PMID- 25960434
TI  - The total amount of uptake may affect the input function: a theoretic approach
      about 18F-FDG PET imaging.
AB  - INTRODUCTION: The aim of this theoretic approach is to establish an analytical
      relationship between the total amount of uptake (TAU), either pathological or
      physiological, and the time constants "alphai" that describe the time decay of
      the tracer input function (IF). The proposed approach uses parameters of a
      (population-based) arterial plasma IF for 18 F-FDG PET imaging. METHODS: A
      previously published formula provides an estimate of the ratio "p" of 18 F-FDG
      molecules that are irreversibly trapped in an 18 F-FDG-positive tissue during a
      whole PET examination, to the number of injected molecules. Then, the change in
      the magnitude of the IF time constants is derived, involving a corrective
      procedure. RESULTS: Trapping of injected tracer molecules affects each alphai
      that is increased by a factor of 1/(1-p), with p ranging between zero and,
      theoretically, less than 1. This result is illustrated in a patient showing an
      intense uptake in the mediastinum at initial staging of a diffuse large B-cell
      lymphoma (DLBCL). CONCLUSIONS: An analytical relationship between TAU and the IF
      time constants is available in 18 F-FDG PET imaging, showing that TAU may
      actually affect the IF.

PMID- 25960435
TI  - Who are maximizers? Future oriented and highly numerate individuals.
AB  - Two studies investigated cognitive mechanisms that may be associated with
      people's tendency to maximize. Maximizers are individuals who are spending a
      great amount of effort in order to find the very best option in a decision
      situation, rather than stopping the decision process when they encounter a
      satisfying option. These studies show that maximizers are more future oriented
      than other people, which may motivate them to invest the extra energy into
      optimal choices. Maximizers also have higher numerical skills, possibly
      facilitating the cognitive processes involved with decision trade-offs. 

PMID- 25960436
TI  - Impact of the January 11 National March on the calls received at the emergency
      medical services centers (SAMU) in Seine-Saint-Denis and Paris.

PMID- 25960437
TI  - [Tongue's tumor].

PMID- 25960438
TI  - [Physician assessment of aptitude for driving in the European Union].
AB  - Road safety is for several years a major public health issue, given the number of
      casualties and annual deaths caused by road accidents in France or Europe.
      European directives of 2006 and 2009 were aimed harmonized community practices
      for the conduct, including medically. We studied the laws in force in each of the
      28 countries of the European Union to make an inventory of the organization on
      this subject. The results showed that 25 countries introduce, at least once,
      including 21 medical check regularly. Age is the main factor that motivates
      control. The frequency of examinations increases with the age of the driver. In
      other countries, a sworn statement of the absence of pathology is enough.
      Although a medical examination is mostly carried out systematically, it the
      content is extremely variable, ranging from a simple vision test to a full review
      with psycho test. Management of professional secrecy is approached differently in
      different countries, although predominantly an exemption exists in the event of
      discovery of the inability of a patient. We note that there is a great diversity
      in the medical screening modalities unsuited to driving. These systems will be
      harmonized to comply with the wishes of European directives. 

PMID- 25960439
TI  - [Vitamin D deficiency prediction by patient questionnaire and secondary
      hyperparathyroidism in a cohort of 526 healthy subjects in their fifties].
AB  - INTRODUCTION: Can vitamin D deficiency be predicted by patient questionnaire?
      Does it lead to secondary hyperparathyroidism that may cause excessive bone
      resorption? We studied non-osteoporotic subjects in their fifties, in whom
      vitamin D levels are often tested. PATIENTS AND METHODS: Patients hospitalised
      for degenerative osteoarthritis or consulting for assessment of menopause,
      without renal failure and not treated with vitamin D, completed a questionnaire
      on sun exposure and underwent measurement of serum calcium, creatinine, 25OH
      vitamin D, PTH and CTX. RESULTS: Five hundred and twenty-six subjects, mean age
      54.6 years (71% women), were investigated throughout the year. 25OH vitamin D
      levels were correlated with sun exposure and varied according to the month of the
      year, unlike PTH and CTX levels. From November to May, over 90% of subjects had
      25OH vitamin D levels<30ng/mL. Of the subjects who did not expose their face,
      arms and legs to the sun for at least 20min/day, 94% had 25OH vitamin D
      levels<30ng/mL. PTH levels were negatively correlated with those of 25OH vitamin
      D. Serum CTX levels were not correlated with PTH or 25OH vitamin D. Only 13% of
      subjects presented with secondary hyperparathyroidism, characterised by serum
      calcium<2.55mmol/L and PTH>65pg/mL, associated with increased CTX levels.
      CONCLUSION: Vitamin D deficiency can be predicted by patient questionnaire. It
      very rarely leads to secondary hyperparathyroidism.

PMID- 25960440
TI  - [Driving and health at work].
AB  - The role of the occupational physician is to prevent occupational accidents and
      diseases. Therefore, he is the one to decide if a worker is fit to drive in the
      context of his professional activity, including in cases where no specific
      driving license is required (e.g. forklift truck, mobile crane). This decision is
      an important one, as two thirds of fatal occupational accidents occur on the
      road. The decision is made on the basis of both a medical examination and the
      regulation, which indicates all contraindications to driving. The physician's
      responsibility is involved, as is the employer's, as he must ensure that his
      employee is fit to drive and possesses a valid driving license at all times.

PMID- 25960441
TI  - [Tumor-like neurosarcoidosis: About one case].

PMID- 25960442
TI  - [Role of the medical officer for the assessment of driving ability. Practical
      aspects, liability and confidentiality].
AB  - Every candidate for a driving license or any driver who meets a health problem
      must, on its own initiative, to submit to a medical examination. The list of
      approved doctors is available in the prefectures. There is a list of medical
      conditions that are incompatible with the licensing or involve restrictions on
      the use of the license. The treating physician is not authorized to carry out the
      assessment of medical fitness to drive for his own patients. This is the prefect
      who decides after consulting a licensed physician or medical committee composed
      of licensed doctors. If it deems medically necessary, the medical consultant
      outside medical commission may request the person to be summoned before the
      primary medical committee whose jurisdiction is then substituted for his.
      Possible advice is: fitness, temporary fitness, fitness subject to the license
      restrictions on use, or the inability of the candidate or driver to drive
      vehicles of the requested class. We emphasize the absence of shared secret
      between the attending physician and the medical officer or the Medical Committee.

PMID- 25960443
TI  - [Neutrophilic eccrine hidradenitis associated with acute myeloid leukemia].

PMID- 25960446
TI  - Arytenoid cartilage chondroma.
AB  - Arytenoid chondroma is an extremely rare benign cartilaginous tumor. We report a
      case of a patient with arytenoid chondroma initially mimicking laryngopharyngeal
      reflux. Clinicians should consider the possibility of the arytenoid chondroma in
      the differential diagnosis of patients with vocal cord palsy, or arytenoid
      swelling caused by laryngopharyngeal reflux. 

PMID- 25960445
TI  - Eliminating mental disability as a legal criterion in deprivation of liberty
      cases: The impact of the Convention on the Rights of Persons With Disabilities on
      the insanity defense, civil commitment, and competency law.
AB  - A number of laws that are associated with deprivations of liberty, including the
      insanity defense, civil commitment, guardianship of the person and numerous
      competency doctrines in the criminal context, require proof of mental disability
      as a predicate. The Convention on the Rights of Persons With Disabilities
      commands signatory states to eliminate that predicate. Summarizing principles set
      out in my book Minding Justice: Laws That Deprive People With Mental Disability
      of Life and Liberty, I explain how this seemingly radical stance can be
      implemented. Specifically, this article proposes adoption of an "integrationist
      defense" in the criminal context, an "undeterrability requirement" when the state
      seeks preventive detention outside of the criminal process, and a "basic
      rationality and self-regard test" for incompetency determinations. None of these
      proposals requires proof of a mental disorder as a predicate condition. 

PMID- 25960447
TI  - Development of a time-resolved fluoroimmunoassay for salmon insulin-like growth
      factor binding protein-1b.
AB  - In salmon plasma/serum, three major insulin-like growth factor binding proteins
      (IGFBPs) are consistently detected at 22-, 28- and 41-kDa. The 22-kDa form has
      been identified as IGFBP-1b and shown to increase under catabolic conditions. We
      developed a competitive time-resolved fluoroimmunoassay (TR-FIA) for salmon IGFBP
      1b. Purified salmon IGFBP-1b was used for biotin-labeling, assay standard and
      antiserum production. The TR-FIA did not cross-react with the 41-kDa form (IGFBP
      2b) but showed 3% cross-reactivity with the 28-kDa form (IGFBP-1a). It measured
      IGFBP-1b levels as low as 0.4 ng/ml, and ED80 and ED20 were 0.9 and 24.6 ng/ml,
      respectively. There appears to be little interference by IGF-I. Using the TR-FIA,
      serum IGFBP-1b levels were measured in individually-tagged underyearling masu
      salmon fed or fasted for 5 weeks, or fasted for 3 weeks followed by refeeding for
      2 weeks. Fasting for 3 weeks significantly increased circulating IGFBP-1b levels,
      while it returned to the basal levels after prolonged fasting for additional 2
      weeks. Serum IGFBP-1b level negatively correlated with body weight, condition
      factor, specific growth rate and serum IGF-I level. During parr-smolt
      transformation of masu salmon, average circulating IGFBP-1b levels were the
      highest in May. There was a positive correlation between serum IGFBP-1b and IGF
      I, which is in contrast to that in the fasting/feeding experiment. IGFBP-1b also
      showed a positive relationship with gill Na(+), K(+)-ATPase activity. These
      results suggest that the relationship between circulating IGFBP-1b and IGF-I
      during smoltification differs from that during fasting and IGFBP-1b may play a
      role in the development of hypoosmoregulatory ability.

PMID- 25960444
TI  - [Evolution since 2002 of the management of patients with ST elevated acute
      coronary syndrome (STEMI) in Ile-de-France. E-MUST survey].
AB  - INTRODUCTION: ST-segment-elevation acute myocardial infarction (STEMI) is a
      therapeutic emergency. Early reperfusion is the key to successful reperfusion.
      Guidelines recommend organizing regional networks. In France, this starts with a
      call to a medical dispatch center, the SAMU-centre 15. The aim of this study was
      to evaluate regional STEMI management using data collected from 2002 to 2010.
      METHODS: Observational, prospective, multicenter survey. STEMI patient with chest
      pain lasting for less than 24hours managed by 40 mobile emergency and
      resuscitation service (SMUR) and 8 emergency medical system (SAMU) from the
      Greater Paris Area (Ile-de-France) were analyzed. Demographic data,
      cardiovascular risk factors, infarction location, decision of reperfusion and
      delays were collected. The rate of coronary reperfusion was chosen as the primary
      endpoint. RESULTS: Eleven thousand five hundred and eighty-eight patients
      enrolled from 2002 to 2010 were analyzed. Median age was 59.9 (51.0 to 72.9)
      years; 9080 (78.5%) were men. The number of patients included decreased from 1376
      in 2002 to 1119 in 2010. Reperfusion was achieved by fibrinolysis in 2644 (23%)
      cases and primary angioplasty in 7999 (69%) cases. The rate of decision of
      coronary reperfusion significantly increased from 86.7% in 2002 to 94.8% in 2010
      (P<0.0001). Interaction between the increasing decision of reperfusion and all
      factors studied (demographics, cardiovascular risk factors, infarct location and
      delays) was significant only for family history of coronary artery disease
      (P=0.03). In-hospital mortality was 2.8% (321 cases). CONCLUSION: The number of
      patients with STEMI managed by the SAMU declined slightly over the past decade.
      The rate of decision of reperfusion progressively increased up to 95%. Entrance
      into the network by the SAMU-centre 15 is a guarantee of a wide and early access
      to the coronary reperfusion.

PMID- 25960449
TI  - OA1 There's plenty of talk about advance care planning but should women be
      listening?
AB  - BACKGROUND: It is well established that populations worldwide are ageing. It is
      also well known that women will continue to live longer than men. Indeed, the
      social gerontology literature describes 'deep old age' as being predominantly
      female. However, little research exists about the gendered implications of
      palliative care. AIM: To provide a feminist critique of attitudes towards and
      perceptions about Advance Care Planning (ACP) amongst community dwelling adults.
      METHODS: Forty-seven women and men (55-93) resident in Auckland, New Zealand and
      members of community organisations participated in seven focus groups. Vignettes
      about individuals with chronic illnesses were used to encourage discussion about
      participants' views on Advance Care Planning (ACP). A feminist gerontology
      framework informed the thematic analysis. RESULTS: Study participants stated
      there is an expectation women will provide end of life care for their partners,
      thus facilitating the partner's option to remain at home. Some women voiced
      concern about how a lack of financial resources, family and social networks
      affected their current wellbeing and shaped their fears for the future. Other
      attitudes expressed highlighted awareness of the physical, emotional and
      financial burden women experience as a result of providing end of life care.
      CONCLUSION: This study, one of the first to adopt and explicitly feminist
      approach to ACP, suggests attitudes towards ACP are highly gendered, while women
      are often caregivers for others at the end of life, their own choices are more
      likely to be circumscribed by living alone at the end of life or being resident
      in aged residential care.

PMID- 25960450
TI  - OA2 Chinese migrant peasant workers and the contradictory demands of filial piety
      in neo-liberal chinese society: a case study of filial end-of-life care in
      langzhong city.
AB  - BACKGROUND: Many scholars claim that recent changes to Chinese society since
      economic reform have challenged longstanding forms of informal social care, such
      as filial piety. For instance there is a societal tension at work in contemporary
      Chinese society today. On the one hand decreasing co-residence in multi
      generational households caused by rural-urban migration, population ageing, the
      fall in fertility and 'One-Child Policy', and women's increasing participation in
      the labour market, emphasises an individualised, wage earning centred society. On
      the other hand, the Chinese government has sought to enforce a form of
      institutionalised filial piety through policies that legally require younger
      generations fulfil the full responsibility of care as there is no
      institutionalised equivalent of the welfare state to provide e.g. home help or
      personal care to the elderly whose relatives live and work at some distance. This
      places many younger generations in the contradiction of having to comply with neo
      liberal labour market demands while also fulfilling state enforced filial piety.
      AIM: This research is to look at how Chinese migrant worker experience perceived
      filial responsibilities in relation to End-of-Life care for parents diagnosed
      with cancer in the current Chinese context. METHOD: My PhD, based on interviews
      with migrant peasant workers caught in this dilemma by the demands of having a
      terminally ill parent, examines how Chinese migrant peasant workers negotiate and
      conduct their filial practices. RESULTS: The preliminary analysis of the
      interviews suggests that 'Filial Piety' is getting reconstructed in multifaceted
      ways as they negotiate the care dilemmas they face. The way they engage with the
      concept of filial piety enables and constrains how they can think about and
      practically organise their parents' care. CONCLUSION: The result would shed a
      light on evaluation of and suggestions for governmental policy-makings, such as
      the newly implemented Parent-Visiting law in China, in terms of better
      reinforcing familial value and equipping end-of-life care, as well as taking into
      account of the specificity of peasant migrant workers' socio-economic status quo.

PMID- 25960451
TI  - WA3 Room for death - international museum - visitors' preferences regarding the
      end of their life.
AB  - BACKGROUND: Just as pain medications aim to relieve physical suffering,
      supportive surrounding for death and dying may facilitate well-being and comfort.
      However, little has been written of the experience of or preferences for settings
      for death and dying. AIM: We investigate preferences for and reflections about
      settings for end-of-life (EoL) in an international sample of museum visitors.
      METHODS: Data derive from a project teaming artists and craftspeople together to
      create prototypes of space for difficult conversations in EoL settings. These
      prototypes were presented in a museum exhibition, "Room for Death", in Stockholm
      in 2012. As project consultants, we contributed a question to the public viewing
      the exhibition: "How would you like it to be around you when you are dying?" and
      analysed responses with a phenomenographic approach. RESULTS: Five-hundred twelve
      responses were obtained from visitors from 46 countries. Responses were
      categorised in the following inductively- derived categories of types of deaths:
      The "Familiar", "Larger-than life", "Lone", "Mediated" "Calm and peaceful",
      "Sensuous", "'Green'", and "Distanced" death. Responses could relate to one
      category or be composites uniting different categories in individual
      combinations. CONCLUSION: These data provide insight into different facets of
      contemporary reflections about death and dying. Despite the selective sample, the
      findings give reason to consider how underlying assumptions and care provision in
      established forms for EoL care may differ from people's preferences. This project
      can be seen as an example of innovative endeavours to promote public awareness of
      issues related to death and dying, within the framework of health-promoting
      palliative care.

PMID- 25960448
TI  - APOE effect on Alzheimer's disease biomarkers in older adults with significant
      memory concern.
AB  - INTRODUCTION: This study assessed apolipoprotein E (APOE) epsilon4 carrier status
      effects on Alzheimer's disease imaging and cerebrospinal fluid (CSF) biomarkers
      in cognitively normal older adults with significant memory concerns (SMC).
      METHODS: Cognitively normal, SMC, and early mild cognitive impairment
      participants from Alzheimer's Disease Neuroimaging Initiative were divided by
      APOE epsilon4 carrier status. Diagnostic and APOE effects were evaluated with
      emphasis on SMC. Additional analyses in SMC evaluated the effect of the
      interaction between APOE and [(18)F]Florbetapir amyloid positivity on CSF
      biomarkers. RESULTS: SMC epsilon4+ showed greater amyloid deposition than SMC
      epsilon4-, but no hypometabolism or medial temporal lobe (MTL) atrophy. SMC
      epsilon4+ showed lower amyloid beta 1-42 and higher tau/p-tau than epsilon4-,
      which was most abnormal in APOE epsilon4+ and cerebral amyloid positive SMC.
      DISCUSSION: SMC APOE epsilon4+ show abnormal changes in amyloid and tau
      biomarkers, but no hypometabolism or MTL neurodegeneration, reflecting the at
      risk nature of the SMC group and the importance of APOE in mediating this risk.

PMID- 25960452
TI  - WA30 The dying well community charter and dying matters: a united kingdom (uk)
      approach to public health and dying.
AB  - BACKGROUND: The Dying Matters Coalition, set up following the UK Government's End
      of Life Care Strategy in 2008, is led by the NCPC (UK umbrella organisation).
      Dying Matters supports changing knowledge, attitudes and behaviours towards
      dying, death and bereavement, and through this to make 'living and dying well'
      the norm. The Coalition has over 30,000 members, and encourages people to talk to
      friends and family about their end of life wishes, including how they would like
      to be cared for, where they want to die and their funeral plans. The Dying Well
      Community Charter is an innovative approach to community development work,
      working with Pathfinder areas to pilot this approach, rather than encouraging
      health and social care services to "do" end of life care "to" people, to
      encourage them to work with community leaders to make end of life care everyone's
      responsibility. AIM: Participants will discover what has worked in the UK,
      including many low resource options, and a community development approach to
      palliative care. METHOD: We worked with 8 Pathfinder communities to ask them to
      pilot the Dying Well Community Charter approach. Dying Matters was the first
      national awareness and behaviour change campaign around death, dying and
      bereavement. RESULTS: Dying Matters has over 30,000 members. Outcome of the
      Charter work is unknown, but more will be known by the time of the conference.
      CONCLUSION: How communities can come together for better death, dying and
      bereavement. That death and dying are not subjects that need to be avoided, and
      can be engaged with for better outcomes.

PMID- 25960453
TI  - OA31 Help or hindrance: how are services and systems viewed by informal care
      networks?
AB  - BACKGROUND: The promotion of community engagement by palliative care services is
      an important strategy in increasing death literacy in the community. Networks of
      support around dying person and their carers can reveal existing death literacy
      or enable its development; this capacity can assist network members to engage
      with health services to the benefit of the dying person and their careers.
      However, it has not been clear whether members of these informal networks view
      palliative care services, and the health system more broadly, as a help or
      hindrance to the networks' support of dying people. AIM: To understand the
      perceptions of members of informal care networks of the role taken by health
      services in the support of dying people at home. METHOD: In interviews with
      carers (N = 23) and focus groups with caring networks (N = 13), participants were
      asked to describe the nature of their engagement with palliative care, other
      health care services and the health system. RESULTS: The analysis revealed care
      by individual practitioners was viewed as "above and beyond" expectations, it was
      clear that individualised and compassionate care was not always achieved.
      Further, the rules and regulations required by many services, and health system
      at large, were viewed as impediments to appropriate support of those dying at
      home. CONCLUSION: More appropriate care of dying people receiving care at home
      requires formal services to evaluate their attitudes and conduct towards informal
      networks. Agenda for incremental health system reform can be identified to remove
      obstacles to engagement between services and community networks.

PMID- 25960455
TI  - OA33 Think ahead.
AB  - BACKGROUND: Think Ahead is a public awareness initiative of the Forum on End of
      Life in Ireland. The Think Ahead Form (www.thinkahead.ie) guides people in
      recording important information in the event that they are unable to speak for
      themselves, due to serious illness, emergency or death. AIM: To engage the public
      to use Think Ahead and to build capacity of community organisations and health
      care professionals to empower people to use the tool if they wish. METHOD: A
      'Think Ahead' form and website were designed and launched as guidance tools for
      the public. A range of processes were also engaged in, including: Public
      consultation Consultation with key stakeholders GP research: involving 120 people
      up to 70 years of age, examined people's experiences of filling in the Think
      Ahead form Nursing home research: involving staff and residents in nursing homes
      in Kildare in 2014 Regional community- based pilots: Regional pilots took place
      in Limerick and Louth, late 2012 Train the trainer programmes with community
      organisations RESULTS: Very positive outcomes for patients and GPs Nursing home
      staff empowered to enable residents to express their preferences 80% of public
      believed that Think Ahead would be of interest to the general public 30,000 forms
      distributed since 2011 Active Retirement Ireland rolling out Think Ahead
      CONCLUSION: The research and public engagement activities have shown that Think
      Ahead is a citizen-led practical tool which people can use as part of their
      planning for end of life.

PMID- 25960454
TI  - OA32 Let's talk about - all ireland survey of palliative care experiences.
AB  - : "During Phase 1 of the Let's Talk About patient experience survey, 367
      responses were submitted by people who use or care (or cared) for someone with a
      serious or progressive life-limiting condition from across the Republic of
      Ireland and Northern Ireland. The overall purpose of the Let's Talk About
      initiative is to gain a better understanding the issues that matter most to
      individuals so that the design and delivery of services and supports can be
      improved and tailored accordingly. The method collects individual narratives
      about a high impact good or bad experience of palliative care services which can
      be accessed at a micro level combined with a meta-analysis of a large quantity of
      qualitative information. Input from users and carers, and specialist and general
      palliative care professional's was reflected in the design of the survey tool,
      during the engagement phase and with the interpretation of the dataset. This is a
      novel approach to identifying the lived experience of users in receipt of
      palliative care which directs focus to the vital aspects of psychosocial
      wellbeing within the palliative care experience. The results have informed
      initial strategic recommendations aimed at a variety of key stakeholders
      including policy makers and commissioners, palliative care providers and agencies
      with a palliative care interest. Phase II of the survey will complete May 2015
      www.letstalk-about.org" Report to reference: Let's Talk About Survey Report:
      Phase 1 http://aiihpc.org/policy-practice/141/phase-i-report/. 

PMID- 25960456
TI  - OA34 Forum on end of life: working to influence policy.
AB  - BACKGROUND: The Forum on End of Life in Ireland was launched in 2009 and has
      conducted a year-long public consultation about end of life issues. A National
      Council was set up to carry out the work of the Forum. Think Ahead is a public
      awareness initiative of the Forum on End of Life in Ireland which guides people
      in recording important information in the event that they are unable to speak for
      themselves, due to serious illness, emergency or death. AIM: The Forum has
      advocated for legislation of advance health care directives and has worked to
      raise awareness among members of the public in relation to their rights.
      Currently in Ireland while common law recognises people's right to express
      preferences and make directives, there has been no legislative framework for
      this, despite European and international law regarding personal autonomy and the
      right to self-determination. METHOD: Organised briefings and information seminars
      for public representatives Organised public meetings and national conferences
      which deal with the importance of advance healthcare directives Spoke of the
      importance of advance healthcare directives and advance care planning as part of
      the Oireachtas (Irish Parliament) Health Committee hearings on end of life Called
      for wider national end of life strategy to take a comprehensive approach to end
      of life issues, including health, legal, administrative, financial and social.
      RESULTS: Advance healthcare directives are provided for in the Assisted Decision
      Making (Capacity) Bill 2013. CONCLUSION: The aforementioned Bill has yet to be
      enacted and there remains work to be done in developing policy in this area.

PMID- 25960457
TI  - OA35 Shared humanity, shared mortality - spiritual care in care homes.
AB  - BACKGROUND: Currently a fifth of the population die in care homes and most
      residents are in the final year of life. Spiritual care is recognised as
      important (The National Institute for Health and Care Excellence [NICE] Quality
      Standards, Leadership Alliance) yet there is little teaching for care homes'
      staff in this vital area. Spiritual care is intrinsic in the Gold Standards
      Framework (GSF) programmes, it is one of the standards for GSF accreditation, yet
      often health and social care professionals are unaware or unconfident in this
      area, with a tendency to confuse spirituality with religion. AIM: To develop a
      Spiritual Care course to supplement the range of GSF programmes, especially for
      care homes, to increase confidence and ability of staff caring for people nearing
      the end of life. While we need to bring professional expertise to bear in our
      caring, we must also bring our humanity, our lack of answers and our ability to
      listen with mindfulness and compassion. METHOD: Working in collaboration with
      Staffordshire University, blending academic and practical expertise, we developed
      a one day workshop and filmed a four-module distance-learning course. RESULTS:
      Evaluations have shown a broadening of awareness and perspective, increased
      confidence in assessing and meeting spiritual needs, greater self-care and
      resilience amongst staff and a more creative interpretation of spiritual care
      helping to meet the needs of care homes' residents. CONCLUSION: Early use of this
      spiritual care workshop and course for care homes' staff has been well received
      and encouraging. Sharing our common human experience of loss and mortality leads
      to greater resilience through inner transformation.

PMID- 25960458
TI  - OA36 The buddy group.
AB  - BACKGROUND: In September 2008 a training course called Sharing the Journey was
      offered at Weston Hospicecare. During the six week course, a number of
      participants were bereaved. Because of the strong relationships developed between
      them they wanted to continue meeting after the six weeks. This highlighted that
      friendships can develop between strangers who are in a similar caring role but
      also sharing the experiences helps bereaved get back into the social networks.
      Having been in a long relationship or a caring role for several years some people
      struggle going out alone. AIM: The aim of The Buddy Group is to support bereaved
      "carer givers" to share their experience and get back into the social network.
      METHOD: The Buddy Group meet on a monthly basis within the Hospice environment,
      and plan their social events together and see it as a safe environment to express
      their emotions. As the groups have moved forward, two carers have assumed the
      role of facilitating the more recent groups and arranging the events. The Hospice
      is utilised for a venue and for support for the carers facilitating the group.
      RESULTS: The Buddy Group was an off shoot from the Sharing the Journey course and
      meet monthly for arranging social activities and supporting their bereavement
      journey. To date 120 people since September 2008 have benefitted from the Buddy
      Group and we are now on Buddy Group 5. Buddy Group 1 and 2 don't attend the
      Hospice but meet outside of the Hospice venue for social networking. Currently,
      the Hospice are operating three groups at the same time and are receiving
      facilitated assistance from two carers that had attended both Sharing the Journey
      and The Buddy Groups. They see themselves as the concept of "caring for the
      carers". CONCLUSION: The development of a Buddy Group may need facilitated
      support from a Hospice professional staff member initially, but after some time
      can become sustained by group members who have experienced the carers role. The
      bereavement journey is supported by fellow group members which results in members
      getting back into the social networks, preventing isolation and loneliness. The
      feedback from group members is extremely positive.

PMID- 25960459
TI  - OA37 Compassionate classrooms: supporting teachers to support children living
      with grief and loss.
AB  - BACKGROUND: Milford Care Centre's social work service is often contacted by
      teachers following a death within the school community. The team recognised the
      need to engage in a more proactive, health-promoting manner to help teachers
      normalise the experience of grief and loss, empowering them to provide support to
      pupils following bereavement. AIM: To develop and evaluate a brief intervention
      for teachers, as part of Milford Care Centre's Compassionate Communities
      programme, to support children experiencing bereavement. METHODS: A five-hour
      experiential workshop was developed and piloted with (1) a group of teachers and
      (2) staff working with early school completion programmes across the City. The
      teacher workshop was evaluated using a pre/post design measuring death anxiety
      and self-reported confidence. A qualitative evaluation, of both workshops will be
      presented from both the facilitator and participant perspective. RESULTS: The
      pilot highlighted that the intervention is acceptable and demonstrated both a
      significant reduction in death anxiety and improvement in self-reported
      confidence for teachers who participated. CONCLUSIONS: The Compassionate
      Classrooms: Working with Grief and Loss intervention can reduce death anxiety and
      improve teachers' confidence. The intervention will be shared with the audience
      for local adaptation.

PMID- 25960460
TI  - OA38 From service delivery to community enablement: a public health approach to
      palliative care.
AB  - : Milford Care Centre is the only hospice in Ireland to make a strategic decision
      to embrace a public health approach to palliative care, through the development,
      implementation and evaluation of the Compassionate Communities Project. This
      presentation seeks to examine why Milford made the decision to move toward a
      community enablement model, describes the development and implementation of the
      Compassionate Communities Project to date, presents key findings from recent
      evaluations and highlights our plans for the future. The presentation uses a
      reflective, story telling approach to meet it's aims, coupled with data and
      statistics gathered from the evaluations, and includes a new short film 'Tell Me'
      developed by recent Computer Science graduates for the Project to use to engage
      with communities during Cafe Conversations. The presentation will highlight the
      relevance of Health Promoting Palliative Care theory to the development of a
      three-tier model of programme activity, examine the challenges in implementing
      such an approach and will discuss the impact of upstream intervention to
      downstream service provision using case studies. 

PMID- 25960461
TI  - OA39 Digging a hole... planting a seed... water it and watch it start to grow,
      grow, grow.
AB  - BACKGROUND: Milford Care Centre's Compassionate Communities Project uses a seed
      grant scheme to engage with communities around illness, dying, death and
      bereavement. The scheme, now in it's 3(rd) cycle strives to inspire and support
      the work of local groups, organisations and individuals who wish to mark in some
      tangible way their response to the universal realities of death, dying, loss and
      care as lived and experienced by those living within their communities. A key
      requirement for the receipt of a grant is that the level of funding must be
      matched either in cash or in kind. AIM: This presentation will report on the
      projects supported, describing the short and medium term impact they have had on
      the local community. METHOD: A short film will showcase the projects. Qualitative
      interviews were conducted with all grant recipients to determine the impact of
      the seed grant at a community level. RESULTS: Seed grants were used in a variety
      of ways, for example: Supporting a community group to develop a reflection space
      Supporting a youth project to explore what death, dying, loss and care means to
      service users through the creative arts. Supporting a library to develop a
      bereavement information 'resource'. Supporting local groups to run a community
      event aimed at increasing awareness and knowledge about 'healthy' ways of coping
      with loss and grief. Supporting those seeking practical ways of providing support
      to other living with illness and loss. CONCLUSIONS: The seed grant scheme offers
      a low cost, high impact approach to working with communities.

PMID- 25960462
TI  - WA40 The good neighbour partnership: why do we need it? who is going to do it?
      how on earth are we going to evaluate it?
AB  - : This one-hour symposium considers Milford Care Centre's Compassionate
      Communities Good Neighbour Partnership and it's evaluation by an international
      team, led by Maynooth University and funded by the All Ireland Institute of
      Hospice and Palliative Care, The Irish Cancer Society, The Irish Hospice
      Foundation and Milford Care Centre. The symposium will be divided into three
      sections: 1. The Good Neighbour Partnership: Why do we need it? In this section
      we will describe the findings from a recent scoping study to determine the social
      and practical needs of community dwelling adults (and their families) living with
      advanced life limiting illness at home. We will consider the rationale for
      specialist palliative care services, working with community groups, to lead the
      development of a volunteer-based social model of care to address unmet need. 2.
      The Good Neighbour Partnership: How do we recruit and train volunteers? We will
      share our process and experience of recruiting and training 15 Compassionate
      Communities Volunteers to assess unmet social and practical need, and to mobile
      the person's circle of community to meet those needs. An understanding of the
      motivating factors of volunteers will be shared. 3. The Good Neighbour
      Partnership: How on earth are we going to evaluate it? Here we describe the
      INSPIRE study - Investigating Social and Practical Supports at the End of life.
      An exploratory delayed intervention randomised controlled trial (framed by the
      MRC Framework for Complex Interventions) to assess the feasibility, acceptability
      and potential effectiveness of the Good Neighbour Partnership. 

PMID- 25960464
TI  - WA42 Proving its worth - changing public policy for palliative care, end of life
      care and bereavement through advocacy and communications.
AB  - BACKGROUND: The 2015 palliative care budget is ?72 million (Euros) but up to ?1.3
      billion spent on end of life care annually - much of this larger figure unplanned
      and uncoordinated. Geographic and other inequities evident in palliative care
      provision. AIM: Build support for the development and implementation of a
      National Strategy on Palliative Care, End of Life and Bereavement. METHOD: Multi
      layered approach to raising awareness and building consensus: Targeting the
      correct audience who can make change happen Presenting robust evidence including
      costs justifying reform and investment Demonstrating that issues affect a
      significant number of people Sharing experience and knowledge Knowing their
      policy priorities Staying resilient - advancing and introducing new angles to
      argument Engaging directly as advocates within the political system at all
      political levels - developing relationships with politicians Identifying
      advocates in the public service to promote policy change Using a variety of new
      and existing projects and programmes Encouraging patients and families to be self
      advocates - using a novel project for discussing and recording future care
      preferences Supporting healthcare professionals to become effective advocates for
      patients Creating alliances to lobby for policy development Using media
      opportunities to sell the message RESULTS: The recognition of the importance of a
      strategic approach to palliative and end of life care acknowledged in
      Parliamentary Committee Report affords an opportunity to develop further policy
      and practice. CONCLUSION: This a long - term exercise, dependent on supporting
      the implementation plan, building momentum and promoting a public dialogue on
      sensitive issues around dying, death and bereavement.

PMID- 25960463
TI  - OA41 How can we support people living with death, dying, loss and care using
      animation? social workers reflect on the compassionate communities 'let's talk'
      films.
AB  - BACKGROUND: Milford Care Centre's Compassionate Communities Project has developed
      a series of animated films - The 'Let's Talk' Series. These films are used by the
      project to encourage people to have think about having difficult conversations
      about illness and death. The films are available on the project website, via You
      Tube and are shown during Cafe Conversations as part of the Compassionate
      Communities Project. More recently, members of the Specialist Palliative Care
      Social Work department have been using the films during their direct work with
      patients and their families. AIM: This presentation aims to introduce
      participants to the Let's Talk film series and describe the learning from social
      workers who have used the films at home, and in the inpatient unit, with
      patients, their partners and their children. METHOD: Social workers were
      interviewed, sharing their experience and reflection on using the animated films
      as a practice tool. RESULTS: A number of case studies will be presented to
      describe the use and impact of the films in practice. CONCLUSION: The films are a
      very useful addition to the social work toolbox. Guidelines for their use in
      practice will be presented.

PMID- 25960465
TI  - WA43 Because i care: an innovative initiative by students in palliative care.
AB  - BACKGROUND: Students in Palliative Care (SIPC), an offshoot of Institute of
      Palliative Medicine (IPM) WHOCC, Kozhikode, Kerala, India is A manifestation of
      community participation in palliative care. A vibrant platform of hundreds of
      student volunteers since 2008. Is engaged in organising affordable support
      program for the palliative care needy. Because I Care (BIC): a grass-root level
      campaign by SIPC to sensitise community on palliative care, engage in patient
      care activities and mobilise resources. AIM: To showcase the idea of: 1. Youth
      involvement in palliative care 2. Explore the possibility of replication. METHOD:
      Structured sensitisation in colleges and training programs for enrolled student
      volunteers. RESULTS: Around 3000 students Reached out to 30,000 people to pass
      the messages of palliative care and mobilise resources. Raised an amount of 1.6
      Million Rupees. Laudable initiatives at regular intervals like Freedom from Pain,
      Signature of Love, Kites of Compassion etc. An international conference on "youth
      in palliative care" is also in store. CONCLUSION: Placing vibrant youngsters at
      the centre of any development processes can result in inclusiveness and
      sustainable participation. The campaign helped the students to identify a genuine
      opportunity to better their own lives and for the community as a whole.
      Participation of student community in palliative care is possible as Social
      participation towards a common public good is always an integral character of
      student communities around the globe. Compassion is a global phenomenon Suffering
      of the patient is almost the same everywhere.

PMID- 25960466
TI  - OA44 Do it yourself care: from diagnosis to crematorium.
AB  - : Our mum was diagnosed, declined and died over a period of two months and one
      week. My siblings gathered from around the globe. We cared for her in her home on
      a small island off the west coast of British Columbia (Canada). She described
      this as the richest period of her life. We shared the care. And her friends, "the
      walkie-talkies" came to support us and to check in on her. We took time for fresh
      air. We walked the beaches. A piece of driftwood inspired my brothers to build a
      coffin. Silk in her studio inspired my sister to create a beautiful shroud. We
      snuggled with her, talked, sang, reminisced. We listened to her stories. And then
      in the quiet of the night, she died. We kept her body at home for a full day. Her
      friends gathered. Then early the next morning, with government permit to
      transport her body, we went via ferry, and drove her down Vancouver Island, past
      the green burial ground that my brother designed to the crematorium. The next day
      the bereavement counsellor greeted us, and with warmth and sensitivity introduced
      us to the staff and the cremator. After a bit of time, we lifted her body into
      the cremator and pushed the button. In Canada, the majority of after death care
      is provided by funeral professionals, but there is a growing interest in the
      concept of do it yourself care for the body and funerals. The purpose of this
      presentation is to share a photo journal of this experience, and depending on
      time allotted, open time for discussion regarding "do it yourself" care. 

PMID- 25960467
TI  - OA45 A different kettle of fish: death literacy.
AB  - BACKGROUND AND AIM: The concept of Death Literacy developed out of strengths
      based practitioner-led research examining the role that social networks play in
      home based end of life care. In this research we started by asking the questions:
      'How are ordinary people supporting each other to care for someone dying at home?
      What happens when they do? How can we capture their stories and illuminate the
      space of the possible? METHOD: Over the past 6 years the Caring at end of life
      research has spoken with over 300 end of life carers, their support networks and
      service providers in interviews and focus groups. RESULTS AND CONCLUSION: While
      caring is often spoke about as a burden and a drain on social capital what
      emerged in this research was that caring for someone at the end of their life can
      be transformational for the carer and their caring network, provided they are
      well supported by a core group of friends, family neighbours, workplaces and
      service providers. It became clear that home, as place of dying, is where caring
      communities can learn about dying and death. Here, it is a community event where
      each person has a role to play. This engaged learning builds death literacy: an
      outcome of engagement in, and participation with, the care of the dying and each
      other. This experience is transformational at individual, network and community
      levels. It is this transformation which we define as 'death literacy, or practice
      wisdom, which anyone can develop. People and communities with high levels of
      death literacy have context specific knowledge about the death system and the
      ability to put that knowledge into practice. Once this happens death literacy
      becomes a resource that people can use for the benefit of themselves, their
      networks and their communities.

PMID- 25960468
TI  - OA46 Dying to know day: a public health campaign in australia.
AB  - : Inspired by the book 'Dying to Know,' Dying to Know Day (August 8) is an annual
      day of action dedicated to bringing to life conversations and community actions
      around death, dying and bereavement. In Australia, 75% have not had end of life
      discussions, less than 10% have an advance care plan and 45% die without a will.
      The Dying To Know Day initiative encourages grassroots action to change these
      statistics by encouraging people to develop their death literacy, make their end
      of life plans, share these wishes with their families and get informed about end
      of life and death care options such as dying at home, home and community led
      funerals and natural burial. 2013 The GroundSwell Project successfully piloted
      and evaluated the concept and in 2014 the initiative grew significantly in size
      to 65 community events and over 120 personal actions across Australia. This
      presentation will provide an overview of this public health initiative and its
      outcomes over the past 2 years. Evaluation data indicates wide-spread support
      across a number of sectors of the community for example palliative care, funeral
      directors, artists and service clubs. 

PMID- 25960469
TI  - WA47 Tweets, hashtags and palliative care: a workshop for social media newbies
      looking to join the digital revolution.
AB  - : A recent article in the BMJ highlighted the role of social media has in
      changing the way we talk about and respond to death and dying. There are so many
      social media channels do you know which ones are best for communicating about
      your work? for networking with peers? participating in journal clubs?
      disseminating research with the international community? What about your local
      community- how do you increase engagement online to promote your work and events?
      How can you use social media to source and access interesting content and
      information about the public health approach? This workshop is designed as a
      beginner level and new user workshop and is suitable for anyone wanting to be
      more active in social media. It is designed specifically to focus on social media
      in relation to the end of life, palliative care and death care online
      communities. Bring your social media device - your phone, ipad or computer and we
      will do the following: login and practice communicating with other users develop
      and implement basic social media goals apply strategies to increase your
      engagement and effectiveness on social media learn simple ways to measure your
      reach. Workshop participants will have an opportunity to build confidence and be
      more effective communicators in social media. You then get to practice your newly
      learned skills for the remainder of the PHPC Conference. 

PMID- 25960470
TI  - OA48 Engaging communities: the impact of a decade of health promoting palliative
      care policy in victoria.
AB  - BACKGROUND: Health promoting palliative care began in Victoria, Australia and has
      been included in Victorian palliative care policy for over a decade. AIM: To
      review the way Victorian palliative care services have responded to government
      policies and strategic directions that are based upon health promoting palliative
      care. METHOD: Thematic analysis of the annual reports of regional palliative care
      consortia over the past two four-year policy cycles. The eight regional consortia
      represent all palliative care services in the state of Victoria, and report their
      activities against the government's strategic directions. RESULTS: Most
      palliative care services report some level of community engagement, but health
      promoting approaches are seldom seen as core business. Community engagement tends
      to be episodic or event-driven rather than sustained and sustainable. Most
      services express a desire to increase community engagement, but report that they
      struggle to do so in the face of the increasing demand for clinical service
      provision. CONCLUSION: The understandings of health promotion and community
      development that inform the current community engagement activities of palliative
      care services need to be expanded. We suggest that this is more likely to happen
      if community groups become active in engaging the health services, including
      palliative care services, rather than by continuing to focus solely on building
      the services' community engagement capacities. Some strategic opportunities for
      accomplishing this reorientation will be identified and illustrated as part of
      the presentation.

PMID- 25960471
TI  - OA49 Disadvantaged dying: a compassionate communities approach for people with
      intellectual disability.
AB  - BACKGROUND: The literature on end of life care in the disability sector is
      sparse, despite deaths in residential disability homes becoming more common as
      the cohort of long-term residents ages. If people with disability are to have
      choice about their dying, both the knowledge and skills of their carers and
      systemic barriers that are embedded in legal structures, policy and service
      systems must be addressed. AIM: In partnership with disability services we aim to
      build sustainable organisational capacity that will equip workers in residential
      disability homes to coordinate dying residents' care according to those
      residents' wishes. METHOD: The attitudes of disability workers toward providing
      end-of-life care for their clients, and their experiences in doing so, have been
      surveyed. The survey identifies both the assets workers bring and the barriers
      they experience in providing end-of-life care. Focus groups have explored these
      findings further in order to develop strategies that build workers' capacity to
      provide end of life support for residents. RESULTS: Results from the survey,
      distributed to over 1000 staff members in north-west metropolitan Melbourne,
      reveal both the relational skills workers bring to their task and their lack of
      training for end of life care. These survey results, and the findings from
      subsequent focus groups, will be presented. The effectiveness of HPPC
      interventions being developed will also be discussed. CONCLUSION: A Compassionate
      Communities approach enhances residential disability care workers' capacity to
      provide end of life care for clients. Numerous structural barriers at the policy
      and service level still need to be overcome if people with disability are to have
      genuine options concerning how, and where, they die.

PMID- 25960472
TI  - WA50 We can't do it alone: hospices and schools working together to educate and
      support children around death, dying and bereavement.
AB  - BACKGROUND: Educating and supporting children around death, dying and
      bereavement, in schools, frequently relies on the individual interest and
      expertise of staff (Rowling 2003). Moves to develop such work of ten results in
      one off projects led by external agencies. Support and education is therefore ad
      hoc and unequitable. A research study was undertaken between a hospice and school
      to develop practice in this area from a health promotion perspective. This
      presentation discusses the design and implementation of two practice innovations
      arising from this process. AIM: The innovations aimed to introduce and educate
      children on issues related to loss and change, whilst simultaneously ensure that
      school staff have the skills and confidence to support individual experiences
      within the school setting. This was from a harm education and early intervention
      standpoint. METHOD: Collaborative inquiry, within an action research methodology,
      was used to advance the innovations. This involved school and hospice staff
      working together to design and facilitate the activities. RESULTS: A programme of
      activities for children aged 5 to 11 (the resilience project) was designed and
      integrated throughout the curriculum. This is currently being piloted. A
      bereavement training programme was designed and facilitated to all school staff.
      Evaluations reported an increase in confidence around supporting bereavement
      issues. CONCLUSION: The process highlighted that combing the skills and expertise
      of hospice and school staff was essential in developing sustainable activities,
      appropriate to the setting. The role of the hospice in engaging with communities
      to collaboratively develop education and support around death, dying and
      bereavement was emphasised. REFERENCE: Rowling, L. Grief in school communities:
      effective support strategies. Buckingham and Philadelphia: Open University Press,
      2003.

PMID- 25960473
TI  - OA51 Caring community in living and dying - engaging communities through
      participatory research, an austrian case study.
AB  - BACKGROUND: The development in hospice and palliative care in German-speaking
      Europe is focused on improving professional practice and specialised palliative
      care services. The project was developed to foster the paradigmatic shift from
      professional - and institution - centred end-of-life care to community-based
      approaches in current end-of-life care in Austria. AIM: The project aims to
      strengthen networks and solidarity in end-of-life care, moreover to foster self
      help resources of older people and family caregivers. Local initiatives and
      projects in diverse community contexts should be developed and supported. The
      process should raise awareness within the local population about existential
      questions concerning vulnerability, frailty, dying, death, loss and grief.
      METHOD: The project follows a multi-level participatory research (Minkler,
      Wallerstein 2003) and community development (Kellehear 2005) approach. Phase 1:
      Describing, analysing and appreciating local care culture. Phase 2: Strengthening
      local networks and self-help resources. Phase 3: Supporting implementation and
      sustainability. RESULTS: The participatory research process was based on the
      dense narratives, micro-stories and care actions of people concerned in order to
      put these in relation to, and expand it with the different perspectives of the
      "circles of care" (Abel et al . 2013). Thus existential and care experiences were
      shared and common knowledge of local care cultures and resources was generated.
      REFERENCES: Minkler M, Wallerstein N, eds. Community based participatory research
      for health. San Francisco: Jossey-Bass, 2003. Kellehear, A. Compassionate cities.
      London: Routledge, 2005. Abel J, Walter T, Carey L, Rosenberg J, Noonan K,
      Horsfall D, Leonard R, Rumbold B, Morris D. Circles of care: should community
      development redefine the practice of palliative care? BMJ Support Palliat Care
      2013:3:383-388. CONCLUSION: The stakeholders succeeded in building relationships
      of trust and in forming "care culture working groups" in various spheres of the
      community. As this is an ongoing project the challenges of social and cultural
      sustainability should be discussed in order to get the citizens involved to an
      even greater extent in gaining 'ownership' of and control over the caring
      community as an ongoing cultural process offering solidarity and compassion in
      living and dying.

PMID- 25960474
TI  - OA52 "ethics from the bottom up": promoting networks and participation through
      shared stories of care.
AB  - BACKGROUND: The "basic action" in creating compassionate communities is to create
      settings where people effectively have the opportunity to develop concerns and
      compassion for each other. The project "ethics from the bottom up" (in Bad
      Bentheim, Lower Saxony, Germany) brings together the relatives of old and dying
      people, professionals from healthcare organisations and people from other living
      and working contexts in order to share their sorrows and care experiences. AIM:
      Current methods and concepts of applied and organised ethical deliberation (or
      ethics "consultation") are not qualified and able to fulfil the requirements of
      ethical questions in the field of health promotion and health promoting
      palliative care. The predominant model of ethical deliberation in healthcare
      settings, the clinical ethics consultation, is designed for the specific
      orientation needs of curative medicine. The analogous step from medicine to
      health promotion, from professional palliative care to compassionate communities
      has not been carried out in ethics. By promoting a compassionate community
      through shared narratives of care and concern, a paradigmatic shift from clinical
      ethics to "communal" ethics is put into action. METHOD: Participatory action
      research design. Ethical approach based on narrative and care ethics. RESULTS: We
      observe a new and simple way to bring relatives into communication with each
      other and with professional and (specialised) health services and to discuss the
      fundamental questions of human life. This is one way of initiating the
      democratisation of care, of finding support in the challenges of weakness and
      dying. CONCLUSION: In contrast to a narrowing tendency in modern ethics/ethics
      consultation (focus on moral dilemmas and treatment decisions) the objective of
      ethical deliberation is not just a singular decision but the sustainable
      cultivation of collective practical wisdom in a web of meaningful relationships.

PMID- 25960475
TI  - OA53 "dementia friendly pharmacies" a community based health promotion project.
AB  - BACKGROUND: Inspired by the Ottawa Charter for Health Promotion, which is a major
      point of reference also for the "Compassionate Communities", we would like to
      propose that communities consolidate various settings like schools, workplaces,
      and health care organisations like community pharmacies, all of which might be
      included in a compassionate communities approach. AIM: We aim at enabling
      community pharmacies to offer informal consulting and support for people with
      dementia and their informal caregivers. Furthermore we want to support pharmacies
      to reach out in the community through various activities. By this means the
      project seeks to contribute to de-stigmatising dementia. METHOD: The project is
      based on the approach "Participatory Health Research" (Hockley, Froggatt, Heimerl
      2013; Wright et al . 2010). The core elements of the approach are participation,
      action and reflection. Approximately 40 staff (almost exclusively women) in 18
      community pharmacies actively participates in the project, i.e. needs assessment,
      interactive workshops, practice projects and evaluation. People with dementia and
      their informal care givers are included in the needs assessment and in different
      steps of the programme. RESULTS: Community pharmacy staff raised several issues,
      closely related to communication, counselling and providing advice in a community
      pharmacy setting: They believe further development of professional practice to be
      important, since dementia care will become a more prominent issue for the
      community pharmacy. Moreover, a high frequency of contact with people living with
      dementia and their caregivers was reported by the majority of staff. Professional
      competencies related to dementia care are a key issue, and community pharmacy
      personnel viewed their practice with a critical eye: Communicating with
      disoriented persons poses some challenges, as does communicating with caregivers.
      CONCLUSION: In the still ongoing project the raised issues are being dealt with
      in practice projects that are performed by the pharmacies with the support of the
      project staff. Several projects reach out to the community through self-help
      groups, cinema performances, public presentations and discussions. Informal care
      givers have engaged in direct contact with the included pharmacies and become
      part of selected practice projects. People with dementia have been included in
      the needs assessment and the design of the project logo.

PMID- 25960476
TI  - OA54 Paying it forward - how participation, care and connexion with our loved
      ones at death leads to future community participation.
AB  - : In this talk I draw from my own personal and professional experiences of
      families gently caring for loved ones after death and wish to show that when we
      are encouraged to remain actively involved in death care and connected to our
      dead that we are empowered to help ourselves and others through the process. I
      plan to use specific, practical examples from a range of home and family-led
      funerals which show that when we embrace death by lovingly participating in this
      way we are enabled to confidently support, guide and give back to our
      communities. This will include the recent experience of woman who felt so enabled
      after washing, dressing and caring for the body of her husband that she hired a
      car and drove his coffin to the natural burial ground the next day. At the
      graveside she led the eulogy and powerfully sang to his coffin as it was lowered
      into the earth by family bearers. Three weeks later the same woman felt so
      inspired that she willingly hired another car and drove the coffin of a stranger
      to the church and crematorium as a simple and kind act of paying it forward in
      the spirit of community. In turn the second widow offered a donation to a charity
      of the first widow's choice. In doing so both families developed and shared a
      close bond which they hope will nourish and sustain them always. In reclaiming
      this lost art of caring for our own and actively participating in this way I
      suggest we can help each other to find purpose, meaning and transform our
      experience as a human community which connects us all in both life and death. 

PMID- 25960477
TI  - OA55 Impact of community health workers for continuum care of palliative care at
      community level integrated in rwanda public health system.
AB  - BACKGROUND: Multi-disciplinary palliative care for patients with any disease is
      rarely integrated into the public healthcare system at all levels in Africa. In
      Kigali, Rwanda, we have developed palliative care services in a district general
      hospital and linked these services to home care using community health workers.
      In addition, the Ministry of Health recently approved a palliative care training
      curriculum for community health workers employed by the government who will
      expand and make sustainable palliative home care. AIM: The impact of Community
      health workers helped the district hospital to map patients with chronic
      diseases, palliative care and identify symptoms for better orientation. METHOD:
      At Kibagabaga Hospital, the public hospital for Gasabo District that includes 60%
      of the population of Kigali, we initiated a training of 481 community health
      workers (CHW), 1 CHW/per village for continuing care and retro-information to the
      District Palliative Care team through Health centre. RESULTS: As of June 2014,
      community health workers had identified 432 patients and report has been sent to
      the district palliative care team for mapping. Anecdotal data indicates a high
      level of satisfaction by patients and family members with palliative care
      assisted at community level and a reduced stress of continuum care. CONCLUSION:
      It is feasible to integrate palliative care for patients at community level into
      public healthcare systems in Africa using Community health workers.

PMID- 25960478
TI  - OA56 Perinatal grief as a deeply social experience: perspectives of bereaved
      parents.
AB  - BACKGROUND: Individual counselling and support groups are the most usual forms of
      support helping professions offer people who are bereaved. This can result in the
      rich social contexts of people's lives being side-lined. Whilst the importance of
      social support is well acknowledged in the literature, it is frequently
      considered as axiomatic and not critically examined. AIM: This study explored how
      parents constructed their experiences of perinatal death and privileged their
      voices and perspectives. METHOD: Utilising a social constructionist, narrative
      approach, nineteen Australian women and men were interviewed within 4-24 months
      of the perinatal death of their baby. Participants were drawn from a community
      rather than clinical sample. RESULTS: Bereaved parents clearly stated they
      required support from their social networks. However this was not always
      forthcoming. In the face of this, some turned to professionals and self help
      groups for support. Some found this helpful; many did not. Parents identified
      wanting support from their own parents, close family, friends and work
      colleagues. They wanted their social identity as parent affirmed and their
      experience acknowledged in everyday life. CONCLUSION: In addition to working
      individually with the bereaved when appropriate, professionals can contribute
      significantly to the wellbeing of bereaved parents by broadening their focus to
      providing support and education to their social systems: the 'natural helpers' in
      the parents' social network. Shifting the gaze will in turn assist the social
      network to better offer support directly, something the bereaved state they want.
      It acknowledges that grief is a deeply social experience and not an individual
      one.

PMID- 25960479
TI  - OA57 The digitalisation of dying, loss and grief on social media channels.
AB  - BACKGROUND: The internet and birth of social media channels have changed the way
      in which we deal with death, loss and grief forever. Our photo albums are now
      saved digitally and shared on Facebook. Our private thoughts are now relayed on
      Twitter. Each year we spend more of our lives online, this workshop will address
      what happens as we approach death and when we switch off. After building a
      relationship digitally they recently presented together at the Macmillan Primary
      Care Conference on the subject 'Can we Palliate Social media'. The outcome of the
      workshop can be viewed below: 'Can we Palliate Social Media' workshop (about) -
      http://deadsocial.org/blog/222-macmillan-primary-care-conference BMJ
      review/results of workshop - http://blogs.bmj.com/spcare/2014/12/04/palliating
      social-media-a-seminar-workshop-at-the-macmillan-professionals-conference-in
      london/ AIM: We will highlight how the digital landscape has changed to help
      evoke thought and discussion around the subject of digitising death. They will
      explore the ethical and moral questions regarding end of life within the digital
      context. The role of the HCP will be examined in relation to social media and
      patient practice. All attendees will be provided with a number of simple tasks to
      carryout online. This will again provide a better understanding around the
      conversations that are occurring online and the digitisation of death. METHOD: An
      interactive 40 min workshop will be directed by us. This will conclude with a 20
      minute discussion. Leaflets containing relevant tasks for HCPs to carryout online
      can be carried out after the workshop. RESULTS: Understanding of the main social
      and digital channels that we (in the UK) use today. Understanding of how online
      channels have changed how we communicate and behave. The different ways grieving,
      remembering and mourning occurs online How death, grief and loss is different
      online Examination of how social media is breaking down the notion of death
      Reflect on how could/should HCPs and EOL professionals engage online in relation
      to EOL matters. Understanding how our digital footprint will ultimately become
      our digital legacy. CONCLUSION: Each participant/attendee will have a basic
      understanding of how death, grief and loss are addressed online within the UK.
      Examples of how different patients (especially children) are using social media
      in hospitals will be provided to help highlight the catalyst for change that
      social media has become.

PMID- 25960480
TI  - OA58 Community capacity development for enhanced hospice palliative care:
      exploring the value of community engagement.
AB  - BACKGROUND: Over time, palliative care has become "professionalised", placing a
      burden on health care systems to manage the suffering of individuals and families
      with advancing, life-limiting illness. The need to develop resources,
      infrastructure and policy to enhance the capacity for communities to facilitate
      and support individuals and families can add value to communities, enrich hospice
      palliative care and reduce health care system burden. AIM: Few examples of
      communities developing such capacity exist, however, this oral presentation will
      describe the results of one study that examined, in one rural community in
      western Canada, key factors that influenced their ability to address their own
      hospice palliative care needs. We will report on factors that helped and factors
      that hindered them in their initial stages of planning for better care. A follow
      up study that is just at its initial stages (i.e. to start in Jan./Feb., 2015)
      will examine the value and outcomes of a model where communities collaborate with
      health care providers to strengthen their hospice palliative care community level
      capacities. In two rural communities in western Canada, such questions asked will
      be: What expertise and infrastructure is required to nurture community-based
      palliative care initiatives? What criteria constitute community engagement and
      leadership in hospice palliative care development? When using a model where
      communities collaborate with health care providers to strengthen their hospice
      palliative care, what are the direct outcomes? And are these of value, and if so,
      in what way, and if not why not? METHODS: The two studies use multiple research
      methods. Both use a case study approach and framework. Results are also generated
      from a systematic literature review; semi-structured key informant interviews and
      focus group interviews. RESULTS: Results from the first study reveal significant
      barriers to a community planning their hospice palliative care needs, such as: a
      lack of provincial guidelines or funds; unforeseen workload; community
      expectations for a hospice building versus improved care; and an overall fear of
      failure. Key factors supporting their planning were: improved community
      awareness; putting hospice palliative 'on the map' at a provincial level;
      substantial donations for new services etc. Although our second, follow study to
      determine more concrete outcomes to community leadership and collaboration with
      health care providers are unknown, we imagine results will speak to the need for
      specific and tangible resources, infrastructure and specific policy direction.

PMID- 25960481
TI  - OA59 Developing an innovative model of palliative care in the community in
      brazil.
AB  - BACKGROUND: Despite a National Policy on Pain and Palliative Care (working since
      2002) and the Family Health Strategy (primary care), Brazil does not have a
      strategy to integrate palliative care in primary care. The Atlas of Palliative
      Care in Latino America (ALCP-2013) did not find any team working with this mode:
      a primary care teach working. AIM: Propose a model of palliative care in the
      Public Health Service of Brazil offered through the Primary Care to community.
      METHOD: The Pilot Project is in the city of Rio Grande, south of Brazil, covering
      the area 29 with 3000 persons. This area has a team with a family physician, a
      nurse, a technical nurse and 6 Community Agents of Health (persons of area who
      work directly with population). The team has 3 aims 1) care: identification of
      possible patients (using the tracking and opinions of community health workers
      and the area diagnostics) > evaluation using PIG and SPCIT > care according to
      needs of these patients 2) awareness and needs assessment of the local/area
      community with ongoing monthly meetings and community engagement 3) awareness of
      management institutions in the city. RESULTS: The project started in November of
      2014 and the first identification found 51 patients. Evaluation and assessment
      will begins and this number will be reduced. The first local meeting will happen
      in January/2015. CONCLUSION: This project seeks to provide a proposal for
      palliative care offered through primary care in a public health service which
      does not exist in Brazil.

PMID- 25960482
TI  - OA60 Public health and palliative care mix; a ccpmedicine approach to reverse the
      overgrowing burden of non-communicable diseases in tanzania.
AB  - : Outline of the Talk: The global prevalence of non-communicable diseases has
      increased persistently affecting developed and developing world. In 2008 alone 14
      million premature deaths were reported globally and it is projected to reach 52
      million by 2030. Diagnosis of NCDs in many of the developing countries [including
      Tanzania] is often made late while the disease progression advances leaving a
      very limited chance for interventions to yield good health outcomes. A recent
      study [2011] conducted in Dar es Salaam, Tanzania on NCDs revealed that, around
      16% of people admitted in referral hospitals had diabetes, and 88% had
      hypertension. The CCPmedicine is a community based private organisation that
      focuses on promoting healthy behaviour practices through prevention of non
      communicable diseases in Tanzania by helping communities to take a leading role
      to promote their own health through health education, early detection of
      diseases, and facilitates timely disease interventions CCPmedicine approach to
      Public Health and Palliative Care mix in addressing the burden of NCDs in low
      resource countries like Tanzania has recently attracted policy makers, and
      practices to engage and support Palliative Care Services. In this paper we seek
      to share our experience of working with the private and public sectors to promote
      palliative care services in Tanzania. 

PMID- 25960483
TI  - PA1 An internal audit into the adequacy of pain assessment in a hospice setting.
AB  - BACKGROUND: Pain is the most common presenting symptom of patients referred to
      palliative services. The effective management of pain is therefore paramount to
      any palliative service. The SOCRATES mnemonic is a pain assessment framework that
      is widely used by healthcare professionals to help them to remember to ask about
      key questions concerning a patient's pain. The eight elements of this framework
      are Site, Onset, Character, Radiation, Associated Factors, Timing, Exacerbating
      and Relieving Factors and Severity. AIM: To assess whether 100% of patients
      admitted to the hospice in a three month period with pain as a symptom were fully
      assessed using all elements of the SOCRATES mnemonic. Furthermore to ensure
      whether these patients were written up for regular and breakthrough analgesia
      medication. METHODS: New admissions from February to April were identified using
      SystmOneTM and their records searched for mention of pain as a symptom and a
      score assigned according to the number of elements of SOCRATES used. The
      medications section on SystmOneTM was checked for the prescription of analgesia.
      RESULTS: The results revealed that 0% of patients were fully assessed using all
      elements of the SOCRATES mnemonic and 66.7% of patients were partially assessed.
      The mean average of SOCRATES elements used when assessing pain was 3.3. Regular
      and breakthrough analgesia were prescribed for 100% of patients who complained of
      pain. CONCLUSION: This hospice meets standards for prescribing analgesia, however
      significantly falls below standards on the assessment of pain using all elements
      of the SOCRATES mnemonic.

PMID- 25960484
TI  - WA4 Volunteering in partnership: a public health approach to delivering
      compassionate care to those at end of life and the frail elderly.
AB  - BACKGROUND: Young people are often denied volunteering experiences with
      vulnerable dying people as this is considered to be 'too distressing'. This
      project challenged this paternalistic attitude and trained young people to
      volunteer in the hospice, and other organisations to enhance the delivery of
      compassionate care. AIM: To promote dignity in care, for older people, people
      with dementia, those at end of life and those with learning disabilities. To
      reduce social isolation and the stigma associated with dying and being old. To
      create new volunteering opportunities for young people to raise their awareness
      of the needs of the dying and the frail elderly. Develop a model of best practice
      - that could be replicated in other parts of the country. METHOD: A health
      promotion approach was used combining education and a community development,
      partnership approach. Results 120 Volunteers delivered over 3,650 hrs of
      volunteering activities, supporting individuals to engage in social activities.
      The project broke myths about having 16-18 year olds volunteering. The
      relationship between the hospice and the local community has strengthened and the
      employability skills for the young people taking part have increased. 16% of
      those who responded to an exit survey had gained full time employment, 9% had
      gained university places. CONCLUSION: The personalisation of care for the frail
      elderly and those at end of life has increased by the use of volunteers. Young
      volunteers need mentoring. Staff needs support to feel confident to utilise the
      volunteers and let go of myths about risks.

PMID- 25960485
TI  - OA5 Empowering ten culturally and linguistically diverse communities in
      melbourne, australia, to access culturally responsive palliative care.
AB  - BACKGROUND: This project addresses low levels of awareness and use of palliative
      care among ten culturally and linguistically diverse (CALD) communities in
      Melbourne, Australia. AIM: To increase awareness, understanding and use of
      palliative care among the Arabic speaking, Chinese, Croatian, Greek, Italian,
      Macedonian, Maltese, Polish, Turkish and Vietnamese communities in Melbourne and
      to strengthen the provision of culturally responsive palliative care. METHOD: In
      July 2013 the palliative care and ethnic peak bodies initiated a two-year project
      with 10 ethnic communities (5 per year) to deliver peer education sessions about
      palliative care in community languages. Adjunct activities include community
      engagement, relationship-building, media, cultural responsiveness education for
      palliative care services, and evaluation. RESULTS: As at mid-July 2014, feedback
      from 837 participants (80% of 1050 attendees) at 37 community education sessions
      for 4 CALD communities indicated that 68% did not know about palliative care
      before the session. 90% had learnt new information, 90% had an intention to tell
      friends and family about palliative care and 90% thought palliative care was a
      good idea. Updated results will be provided. CONCLUSION: Participatory and
      engagement strategies are needed to improve awareness of palliative care among
      CALD communities. The formation of community reference groups is a valuable
      strategy that respects community leadership, expertise and networks. The
      participation of CALD communities in tailoring education and information to meet
      specific cultural, spiritual and linguistic needs is essential. The participation
      of palliative care services in project activities is valued and strengthens
      relationships of trust and understanding.

PMID- 25960486
TI  - OA6 Talking about death won't kill you; introducing die-alogues.
AB  - BACKGROUND: Death holds a significant place in societies despite not being a
      direct or first-hand experience for many. Fewer people now die in their homes
      surrounded by family, and we have distanced ourselves from death by geography and
      the medicalisation of death. Our understanding of dying and death is influenced
      by the communities we live in. AIM: Die-alogues is an initiative hosted by
      Hospice Northwest intended to support meaningful conversations about dying,
      death, life and living. The mission of Hospice Northwest is to support end-of
      life care in our community. By engaging in open, easy and respectful discussions
      about death and dying ourselves, we can better prepare ourselves to care for
      others as they face their own dying and that of those they love. METHODS:
      Responding to an identified community need, we have partnered with community
      organisations including a music and dance studio, a leadership group and a
      research centre to facilitate this initiative. Our approach has been innovative
      and included a flash mob, Jeopardy games and various other strategies to
      facilitate and support community members' discussions of living until we die.
      RESULTS: Evaluations are positive. Our community has requested more opportunities
      for Die-alogues to continue. This initiative will hopefully expand in our region
      including within neighbouring First Nations communities. CONCLUSION: Our standing
      room only events demonstrate that our community wants to engage and be active
      participants in learning about dying and death and supporting one another. This
      presentation/poster will share some of the lessons learned from the Die-alogues
      community engagement process.

PMID- 25960487
TI  - WA7 Refining and sharing our methods - how to research the public health approach
      to palliative care?
AB  - : According to the WHO, public health has a mandate to: 1) Assess and monitor the
      health of communities and populations to identify health problems and priorities,
      2) assure that all populations have access to appropriate and cost- effective
      care, 3) devise public policies and actions to solve identified local and
      national health problems and priorities. In line with this, public health has
      increasingly provided a framework for descriptive and epidemiological palliative
      care research, related to the first two mandates. Demographic, epidemiological,
      and sociological changes are increasingly asking for a broader public health
      approach to palliative care research, one that incorporates the principles of
      health promotion. This workshop will be led by an international collaborative
      group interested in how these different mandates relate to one another in
      developing a public health and palliative care research agenda. The first
      presentation will focus on the more traditional public health and epidemiological
      research approach and how it has addressed some public health challenges in
      palliative care but has missed or ignored others. The second presentation will
      focus on the New Public Health approach and how this has been translated into
      research evaluating health promoting palliative care and related interventions,
      but faces the major challenge of developing an appropriate thorough
      methodological and evidence base. The presentations will examine the contribution
      of each tradition and determine how they can inform and strengthen one another.
      The workshop will conclude with a panel discussion to engage participants to
      develop a research agenda for the future. 

PMID- 25960488
TI  - PA2 Satisfaction with information received: perceptions of the patient and the
      informal caregiver.
AB  - BACKGROUND: Provision of information to patients and families is a priority of
      palliative care. Lack of information on symptoms, treatment and disease progress
      adversely affects patients' and caregivers' abilities to self manage and
      participate in decision making and care. Qualitative reports of end of life care
      suggest caregivers seek more information than patients. Ignorance of this need
      may hamper health promotion strategies and limitation of patient and caregiver
      morbidity during end of life and bereavement processes. AIM: To compare
      satisfaction of dying patients with information given; to proxy satisfaction
      estimates on the patient's behalf. METHODS: Prospective study comparing
      assessment of satisfaction with information received by nurse, informal caregiver
      and dying patient (>64 years) in hospital. Assessments made within 24 h, using
      patient and caregiver versions of the palliative outcome scale (POS). STATISTICAL
      ANALYSIS: weighted kappa for agreement between proxy and patient. RESULTS:
      Informal caregivers overestimate dissatisfaction with level of information given
      compared to patients. Weighted kappa patient versus ICG 0.187 (slight agreement),
      n = 50. CONCLUSION: The disparity between patient and proxy information
      satisfaction reflects the complexity of participatory strategies to limit
      morbidity at the end of life. Proxy over- estimation of patient dissatisfaction
      with information received may reflect the caregivers own dissatisfaction. As
      death approaches, caregivers require more information than patients, their burden
      increases and they become the interpreter of patient symptoms. Ignorance may lead
      to overestimation of symptoms, early breakdown of social care, and unplanned
      admission, risking death other than in the patients preferred place. Meeting
      caregiver information needs may reduce caregiver burden and improve proxy
      assessments, reducing patient and caregiver morbidity.

PMID- 25960489
TI  - PA3 Using the lived experience of volunteers to enhance the care of dying
      patients and their families.
AB  - BACKGROUND: In the UK, the majority of people die in hospital.(1) Community
      presence is considered to be a significant component to achieving a "good
      death",(2,3) however many patients die with no/few visitors, spending their last
      weeks of life isolated or alone. AIM: To establish a Volunteer Service and offer:
      A presence to dying patients. A connexion to the community outside the Hospital.
      Support to families, unable to visit or emotionally exhausted from their bedside
      vigil. METHODS: The Service was piloted on 6 wards (October 2012-March 2013)
      within a large NHS Trust, in the North of England. This was followed by a
      comprehensive evaluation, according to MRC guidance. RESULTS: Analysis of the
      service evaluation indicated that the service was extremely beneficial, meeting
      its aims in providing an emotional support and spiritual presence to dying
      patients, and their families. CONCLUSION: The Service provides a model of best
      practice that could be replicated in other Trusts and within other care settings.
      There are plans to further develop and expand service provision across the Trust.
      REFERENCES: National End of Life Care Intelligence Network. What we know now.
      2013. http://www.endoflifecare
      intelligence.org.uk/resources/publications/what_we_know_now_2013 Department of
      Health. End of Life Care Strategy. 2008.
      https://www.gov.uk/government/publications/end-of-life-care-strategy-promoting
      high-quality-care-for-adults-at-the-end-of-their-life Kellehear A. The end of
      death in late modernity, an emerging public health challenge. Crit Public Health
      2007;17(1):71-79.

PMID- 25960490
TI  - PA4 The companion volunteer service.
AB  - BACKGROUND: Recruitment and training of Companion Volunteers has developed out of
      a Companion Sitter Training Programme begun in 2010. (Scottish Journal of
      Healthcare Chaplaincy Vol 15. No 1, 2012). This programme was established to
      support patients emotionally and spiritually. While other services were available
      to offer practical support, this appeared to be unique in its delivery method.
      Within Weston Hospicecare, the feedback from patients and their carers encouraged
      us to develop a small team of trained volunteers to act in the role of Volunteer
      Companions. The Companions would be tasked to go in to patient's place of
      residence, in a non-medical support role, to converse, reminisce, and share
      outlooks while providing company and contact. AIM: The aim of this project is to
      offer emotional support which sustains patient care in their chosen environment
      and enables those in a caring role to maintain these choices. METHODS: Companion
      Volunteers go through the volunteer process of the Hospice and then join the
      specific training sessions for this role to offer support to patients and those
      in a caring role. Companion Volunteers were already encouraging carers to look at
      community networks and to say yes to offers of help. The extended role of the
      Companion allows for a total view of both parties' needs to discuss through the
      developing relationship of trust and care that is established by regular contact
      and support. Further training sessions are attended to develop changes to the
      role and supervision allows for support and discussion for volunteers. RESULTS:
      30 Companions are currently supporting one or more patients in a variety of ways
      depending on patient/carer needs. Feedback is suggesting that companion support
      is valued for its non-medical emphasis and normalising of the situation.
      CONCLUSION: Companion volunteers are now fully integrated into hospice care and
      support. They are valued for their ability to be present in complex clinical
      situations, offering sustainable and regular support which upholds patient and
      carer choices.

PMID- 25960491
TI  - PA5 Elderly population in bangladesh: coping with society in transition.
AB  - BACKGROUND: Bangladesh has a long tradition of looking after the elderly by
      offspring or family. But rapid socio-economic transformations, changing social
      values have broken down the traditional extended family system. Many elderly
      people now stay in old age homes, mainly based in Dhaka, run by non-government
      organisations or as a charity. AIM: This paper explores the scenario of the
      elderly's reasons for living in old age homes, coping with new environments and
      satisfaction about old age homes, and to sensitise the policy makers for
      designing and implementing appropriate programs for the elderly in Bangladesh.
      METHODS: Elderly (65+ years) living in two old age homes (n = 56) in Dhaka were
      interviewed. Reasons for staying in home and satisfaction etc. along with socio
      demographic information were collected. RESULTS: Almost all came from better off
      families, 47% male and 53% female. 68% of men and 36% of women were retired mid
      and high level officials. Reasons for coming to elderly home were problems with
      kin (63%) or with children (9%), children living in abroad (5%), no one to take
      care of them at home (67%), burden on the family (24%), properties occupied by
      others (27%). Children or relatives visit them (87%). 92% are satisfied with
      overall management of old age home. CONCLUSION: Elderly people living in old age
      homes are mainly from better off urban middle-class and rich families. It does
      not reflect the real situation of the elderly in the society. The old age home is
      a new idea or one answer of the elderly in a society in transition. It demands
      further wide ranged research; however findings reflect the indication of the
      growing rift between generations.

PMID- 25960492
TI  - PA6 Death chat: engaging with dying and death.
AB  - BACKGROUND: Talking about death continues to be a social taboo. St Christopher's
      has a large, welcoming social space, (The Anniversary Centre) and is committed to
      opening up its buildings in a number of ways. The St Christopher's social
      programme, of which Death Chat is part, aims to break down social taboos. AIMS:
      Hospices have a responsibility to engage creatively with patients, family
      members, carers and the wider community. Death Chat, held in the hospice
      buildings, enables honest discussion about dying and death and topics surrounding
      these themes. METHODS: Death Chat meets weekly and is an open meeting that takes
      a different subject each week as the starting point for conversation. Cheese and
      wine are shared and participants quickly find a place in the group. RESULTS:
      Death Chat has attracted patients, family members, bereaved relatives and the
      community since September 2013. Attendees have reflected that coming has broken
      taboos. Peter said, 'it's nowhere near as depressing as it sounds; it's a nice,
      friendly atmosphere - a convivial place.' Molly found Death Chat to be a
      welcoming, open and challenging space, 'I have learnt that death is more about my
      attitude to life than anything else. It has been by far the most important lesson
      I have learnt since dealing with bereavement.' CONCLUSION: Death Chat provides a
      forum in which discussion of dying and death for recognises that these are social
      events and reclaims them from being taboo, to being a normal part of life's
      experience.

PMID- 25960493
TI  - PA7 Developing a culture of medication safety in the palliative care home setting
      - supporting choices in place of care and death.
AB  - BACKGROUND: It is common informal practice in Australia for carers to be trained
      to administer PRN subcutaneous medications, especially in the last few days of
      life. A safe, legal and ethical framework for practice was needed to support end
      of life decision-making. AIM: To develop a culture of safety in the palliative
      care home setting by applying a Health Promoting Palliative Care philosophy,
      Kellehear (1999), to enable choice in place of care and death. METHOD: Team
      brainstorming and literature review - developed: Carer education programme to
      evaluate a carer's preparedness to administer subcutaneous medications. Guideline
      Evaluation and Communication strategy Support Focus Ease of access to equipment
      Piloted 2009 RESULTS: Pilot 93% participants achieved wish to die at home -
      consistent at approximately 90% medication errors reduced. Carer confidence
      increased to confident and most confident. Hospital admissions reduced - remains
      approximately 8-10% of all days on service spent in hospital. Staff safety and
      satisfaction increased with reduction in after-hours home visits - averages
      remain at one or two per year. After-hours phone calls did not increase in
      response to practice changes. CONCLUSION: Health promotion, enablement and
      promotion of autonomy and support rather than control and disablement are
      powerful determinants of carer's ability to cope when caring for the dying, and
      enduring bereavement. This project is now standard practice and has transformed
      community practice of palliative care empowering consumers and health
      professionals with such potential. However, in response to criticism of this
      practice the carer's perspective will be captured in a carer survey.

PMID- 25960494
TI  - PA8 St joseph's hospice's newham bereavement service.
AB  - BACKGROUND: In 2008 Newham ranked the 2nd in the country for income deprivation,
      Newham's Census showed 144 languages spoken and the lowest employment rate
      compared to other London Boroughs. The Newham Bereavement Service was set up in
      September 2012. It has been commissioned by NHS East London and City for 3 years.
      Volunteers have been trained to provide bereavement support. This initiative
      enabled a network of volunteers to support their community during bereavement and
      allow those who might not access professionally led services to get the support
      they need. AIM: As hospice care moves into a more community based approach, St
      Joseph's Hospice's Newham Bereavement Service has modelled a service providing
      bereavement support for and by local people. This service is a working
      partnership between St Joseph's Hospice and Newham Talking Therapies where
      volunteers are trained and supported to deal with complex bereavement referrals
      in one of the most deprived areas in the UK. The service has been the subject of
      research conducted by Which?, The charity and Consumer's Association.
      METHODOLOGY: The study was based on semi-ethnographic qualitative approach,
      designed and carried out in close discussion with Newham Bereavement Service
      staff and academics. During 2013-14 Which? Conducted participant observations of
      the recruitment, training and supervision process of volunteers. Following this
      Which? conducted 21 semi-structured telephone interviews with services users and
      befrienders, and with managers and staff on the programme. RESULTS: The Newham
      Bereavement Service is described as on the 'crest of a wave' in an area where
      people are realising that joint partnerships between public service providers and
      local communities can have a significant impact on complex psycho-social issues.
      CONCLUSION: This report places the Newham Bereavement Service within a policy
      context illustrating a new approach to service delivery where budget constraints
      and cuts in health and social care have required a community based solution.

PMID- 25960495
TI  - PA9 Developing a palliative hub: lessons from the island of ireland.
AB  - BACKGROUND: Meeting the information needs of entire community including patients,
      families, carers, health and social care professionals and researchers is
      important in a society where online resources are an increasing source of
      information. Providing this information digitally on one location will reduce the
      burden on individuals trying to navigate the internet and multiple sources of
      information, which may not be appropriate or relevant. AIM: To develop The
      Palliative Hub as a gateway for information, education and guidance regarding
      palliative care. METHODS: Drawing on the skills and expertise of a range of
      stakeholders, working groups were established, which represented service users,
      carers, providers, charities and advocacy groups. The purpose of these groups was
      to assist with the design and development of the Palliative Hub, as sites to
      provide information, education and guidance about palliative care. The Palliative
      Hub, whilst providing information, also acts to filter and direct the user to the
      most relevant sources of further information. RESULTS: It is anticipated that
      this resource will assist with meeting the palliative care information and
      education needs of the entire community in one place with key signposts to
      relevant sources and resources. CONCLUSION: The Palliative Hub has the potential
      to become an integral element in meeting the palliative care information and
      education needs of the entire community and is an example of an innovative and
      collaborative project across the island of Ireland, which could be translated
      across other jurisdictions.

PMID- 25960496
TI  - PA10 What i need you to know. building a collaborative communication tool.
AB  - BACKGROUND: During strategy consultation in Northern Ireland an "End of Life Care
      Passport" was suggested as a way to address myriad communication difficulties
      involved in living with evolving illness. AIM: To build a patient-owned
      communication tool to facilitate important conversations and capture key
      information as health changes. METHODS: Participatory action methods used to
      engage service users, carers, patient advocates, and healthcare professionals.
      Views harnessed via: face to face, email, telephone, via series of workshops.
      Iterative process of drafting, dissemination, evaluation, re drafting. Pilot
      version launched (350 disseminated): used for a 3 month evaluative period by 3
      groups: living with dementia, with motor neurone disease, with advanced
      respiratory illness. Feedback widely sought from participating individuals and
      groups. RESULTS: The emergent tool(1) very different from originally envisaged.
      Key issues include widespread rejection of "End of Life Care Passport" (felt to
      be professionally based perspective); very high level of engagement with the
      process, imperative to develop a tool which focusses on language and
      communication needs of patient and carers rather than professionals. Emergent
      tool contains ten sections and brief explanatory content. Housed as A5 portable
      ring binder (e-version suggested), updated collaboratively by patient, carers,
      key supporters, professionals. CONCLUSION: Patients and carers face multiple
      communication difficulties negotiating changing health. At particular risk are
      those with rare illness and those whose capacity is limited due to illness,
      language or cultural barriers. There is a role for a communication tool which
      houses key evolving information, is completed collaboratively and patient owned
      and controlled. REFERENCE: http://www.rcgp.org.uk/rcgp-near-you/rcgp-northern
      ireland/my-healthcare-passport.aspx.

PMID- 25960497
TI  - PA11 The dreamers - life, death and dreams.
AB  - BACKGROUND: Palliative Care Victoria is building community capacity to have end
      of life conversations. AIM: To create a conversation resource. METHODS: In
      partnership with Pippa Wischer, we published The Dreamers, an exploration of
      life, death and dreams through interviews and photographs of forty palliative
      care patients. RESULTS: The Dreamers was an effective advocacy tool during the
      2014 Victorian State Election. Palliative care services are using it with
      patients and families. The photographs are being exhibited at a rural regional
      gallery with several other galleries expressing interest. Other applications are
      being explored (e.g. conversation cards). CONCLUSION: The Dreamers highlights the
      importance of personal stories in overcoming the taboos around death and the
      value of the arts to foster community engagement and social change.

PMID- 25960498
TI  - PA12 Is digital storytelling ka pai for new zealand m&amacr;ori? using digital
      storytelling as a method to explore wh&amacr;nau end of life caregiving
      experiences: a pilot study.
AB  - BACKGROUND: M&amacr;ori regard stories as a preferred method for imparting
      knowledge through waiata (song), moteatea (poetry), kauwhau (moralistic tale),
      pakiwaitara (story) and purakau (myths). Storytelling is also an expression of
      tinorangatiratanga (self-determination); M&amacr;ori have the right to manage
      their knowledge, which includes embodiment in forms transcending typical western
      formulations. Digital storytelling is a process by which 'ordinary people' create
      short autobiographical videos. It has found application in numerous disciplines
      including public health and has been used to articulatethe experiences of those
      often excluded from knowledge production. AIM: To explore the use of digital
      storytelling as a research method for learning about wh&amacr;nau (family)
      experiences providing end of life care for kaum&amacr;tua (older people).
      METHODS: Eight M&amacr;ori and their nominated co-creators attended a three-day
      digital story telling workshop led by co-researchers Shuchi Kothari and Sarina
      Pearson. They were guided in the creation of first-person digital stories about
      caring for kaum&amacr;tua. The videos were shared at a group screening, and
      participants completed questionnaires about the workshop and their videos. A
      Kaupapa M&amacr;ori narrative analysis was applied to their stories to gain new
      perspectives on M&amacr;ori end of life caregiving practices. (Kaupapa Maori
      research privileges Maori worldviews and indigenous knowledge systems.) RESULTS:
      Digital storytelling is an appropriate method as M&amacr;ori is an oral/aural
      society. It allows M&amacr;ori to share their stories with others, thus promoting
      community support at the end of life, befitting a public health approach.
      CONCLUSION: Digital storytelling can be a useful method for M&amacr;ori to
      express their experiences providing end of life caregiving.

PMID- 25960499
TI  - PA13 The arts and end of life conversations: an innovative approach to health
      promotion in palliative care.
AB  - BACKGROUND: Dying in Australia has been recognised as amongst the most
      institutionalised in the world. Discussion of death and dying is largely taboo in
      contemporary society, resulting in a lack of formal advance care planning or
      personal reflection on end-of-life considerations. To address this problem, a
      pilot study was developed as an innovative health promotion activity, drawing
      upon the Arts. AIM: To explore how an arts medium might influence public
      discussion on end of life issues in the community. METHODS: An action research
      approach was used to collect survey data from a community sample attending a
      Canberra marketplace. 54 participants completed a 14 item questionnaire, after
      viewing a photographic exhibition that provided international narratives on death
      and dying. Qualitative descriptors were elicited from participants to describe
      their reactions to viewing the exhibition, and quantitative data were analysed
      for frequency. RESULTS: Most participants agreed the exhibition effectively
      engaged members of the public in conversations about death and dying. After
      viewing the exhibition, they were more inclined to consider or prepare a legal
      will, enduring or medical power of attorney, or an advance care plan (ACP).
      CONCLUSION: From this pilot study, there are preliminary but encouraging data to
      suggest that the Arts are an effective medium for health promoting approaches. We
      propose further use of Arts-based activities in communities to promote public
      discussions about death and dying.

PMID- 25960500
TI  - PA14 The legacy of cancer: why a health promoting approach is so important in
      palliative care.
AB  - BACKGROUND: A diagnosis of cancer and anticipated death of a loved one has a
      significant impact on the whole family. Research has mainly focused on carers,
      with little emphasis on the wider, long-term implications. AIM: To explore the
      cancer beliefs of patients with advanced cancer and their relatives. The focus
      was on their lived experiences and how these affected their beliefs, attitudes
      and constructions of cancer risk. METHODS: 27 in-depth, semi-structured
      interviews were conducted with advanced breast, colorectal or lung cancer
      patients and their close relatives. Interviews were recorded and transcribed
      verbatim. Data was analysed using the constant comparison method. RESULTS: A core
      category of fear, helplessness and fatalism emerged from the data. Family history
      was the most salient cancer risk factor and a diagnosis of advanced cancer
      increased perceptions of vulnerability for first-degree relatives. For relatives,
      the uncertainty and chaotic loss of control that accompanied an advanced cancer
      diagnosis resulted in multiple levels of fear and intensely negative or
      fatalistic attitudes to cancer. In contrast, patients held less negative views of
      cancer. They described several means of regaining control, including the
      importance of leaving a legacy - the hope that their situation would have a
      positive impact on others in the future. CONCLUSION: Despite the prominence of
      'prevention' in definitions of palliative care, services have evolved that are
      largely professional led and reactive. Adopting a health promoting approach based
      on empowerment is important, not just for improving care, but also increasing
      perceptions of control that may reduce negative cancer beliefs.

PMID- 25960501
TI  - PA15 Beer mat chat.
AB  - BACKGROUND: Storytelling/remembrance can the reduce isolation of recently (and
      less recently) bereaved people, and are beneficial to participants. Traditional
      rituals and approaches which supported storytelling/remembrance are declining in
      Scotland. Pubs are hubs of social interaction and storytelling, especially for
      men. AIM: To explore the acceptability of beer mats in pubs as a prompt to
      storytelling and remembrance of people who have died, and to promote To Absent
      Friends, a peoples' festival of storytelling and remembrance. METHODS: 5 mats
      were designed - each had a carefully selected quotation or piece of trivia
      relating to loss or remembrance, plus a web link to www.toabsentfriends.org.uk.
      20,000 mats were made available to order. Feedback regarding acceptability was
      elicited through conversation with bar tenders, direct observation and a
      questionnaire dispatched with some orders. A press release was issued. RESULTS:
      The mats were generally viewed as being acceptable. A local brewer distributed
      Approximately 15,000 mats to pubs across Edinburgh. The main Edinburgh newspaper
      ran a prominent article about the mats, the To Absent Friends Festival and the
      value of greater openness about death and dying. CONCLUSION: Beer mats are an
      acceptable way of introducing reflection on loss, grief and mortality into pubs.
      More research is needed to establish the effectiveness of the mats in prompting
      storytelling and remembrance.

PMID- 25960502
TI  - PA16 Carer proofing: empowering family carers to design an online tool to meet
      their information needs.
AB  - BACKGROUND: Among the general public there are misconceptions, sensitivities and
      taboos relating to Palliative Care. Furthermore, many Palliative Care recipients
      and Family Carers are managing with little guidance, knowledge or training. AIM:
      The All Island Institute for Hospice and Palliative Care (AIIHPC) funded this
      research to identify and evaluate community learning needs in the context of
      Palliative Care and propose key components of an electronic learning package and
      supporting materials for local communities on the island of Ireland. METHODS:
      This research emulated a participant action research model which was developed to
      create an empowerment intervention for older people to protect themselves against
      financial abuse.(1) The model is guided by principles of authentic participation
      and collaboration; namely through interviews and focus groups with care
      recipients and Family Carers with experience of Palliative Care as well as with
      relevant health care professionals. The research also assembled a working group
      of Family Carers. RESULTS: The working group of Family Carers was supported and
      empowered to reflect on their personal experience, on the insight from Health
      Care Professionals and on creative methods of information delivery. The Working
      Group made specific recommendations about the content of an online learning
      package and the delivery mechanisms that would best meet the information needs of
      those new to Palliative Care. CONCLUSION: Placing Family Carers at the centre of
      the research process resulted in pragmatic recommendations and should result in
      the design of an effective online information tool. REFERENCE: The O'Donnell
      Empowerment Model, NCPOP, UCD http://www.ncpop.ie/WEAAD_2013_Presentations.

PMID- 25960504
TI  - PA18 Heart of gold. integrating cross boundary care across different sectors with
      patients at the heart of care - a population-based public health perspective.
AB  - BACKGROUND: In response to the growing challenge of over-hospitalisation and
      fragmentation of care for people nearing the end-of-life, a key factor is to
      develop an integrated cross-boundary care approach to meet the population's
      needs. Gold Standards Framework (GSF) quality improvement programmes are widely
      used in the UK in primary care, care homes, hospitals, domiciliary care and
      hospices. By working together to a common plan, GSF can help be a vehicle for
      improvement with patients at the heart of care. AIM: To explore using GSF
      programmes in different settings to develop an integrated whole-system approach,
      with patients at the heart of care - the 'heart of gold' projects. METHOD: A
      description of GSF used in different settings as a common language to develop
      better integrated cross-boundary care, with peoples' wishes and preferences at
      the heart of care. GSF improves the early identification, Advance Care Planning
      discussions and coordination of care reducing unnecessary hospital admissions.
      RESULTS: Findings from different sectors are presented from each setting, looking
      at whole-systems, and practical and qualitative measures of progress. CONCLUSION:
      Real improvements are being seen across whole areas using GSF as a vehicle for
      better co-ordinated care. 'Gold patients' and their families feel many benefits
      and there is greater openness and 'cultural change' in end-of-life-care,
      especially for the frail elderly. GSF can be part of the solution in developing
      such integrated care by developing a common 'vocabulary' of care for all people
      in any setting with any condition in the final years of life.

PMID- 25960503
TI  - PA17 Interventions to improve upstream communication about death and dying.
AB  - BACKGROUND: Death is universal. Only 37% of adults have a will and 48% have
      stated their wishes regarding cremation or burial.(1) Planning and communication
      can help prevent some of the distress associated with dying and bereavement. AIM:
      To evaluate an intervention to encourage people to plan for the end of their life
      and to communicate their wishes to those closest to them. METHOD: Two
      interventions were delivered via community groups: 'Awareness' presentations
      aimed to raise awareness of benefits of preparing and talking about end of life
      issues. 'How to' workshops aimed to give people confidence and tools to open
      relevant conversations. To evaluate their impact, we conducted a 3-stage
      questionnaire survey; administered before, immediate after and 3 months after
      events. RESULTS: At baseline (n = 498; 76% female) 76% had previously discussed
      end of life care or wishes after death. Most were comfortable talking about these
      subjects, giving a mean score of 8.28/10. At follow-up (n = 133); 60% indicated
      they had made changes following the event; 43% had talked about their own end of
      life wishes, 9% for the first time; and 39% reported making other changes. The
      change in the proportion of people who had ever talked about their own end of
      life wishes was statistically significant (p = 0.033). CONCLUSION: Well designed
      community events can improve planning and communication of end of life
      preferences among general population. REFERENCE: Dying Matters Survey
      http://www.comres.co.uk/polls/Dying_Matters_Public_April12.pdf.

PMID- 25960505
TI  - PA19 'closing the gap': a community engagement project.
AB  - BACKGROUND: Dove House Hospice serves a population of about 600,000 covering Hull
      and East Riding. About 42% of people in Hull and East Riding die in their usual
      residence. Dove House Hospice's vision is to provide excellent specialist
      palliative care and support to patients, their families and carers in the
      locality. Despite excellent services provided, there was evidence of lack of
      awareness. A project, using a community engagement approaches, was therefore
      developed to close this gap. AIM: Raise awareness about death, dying, loss and
      care; and services provided by Dove House Hospice Improve partnerships between
      Dove House Hospice and the community. Increase social supports to those who
      experiences death, dying, loss and caregiving. METHODS:  APPROACH: Two postcode
      areas, namely Cottingham and Bransholme, were initially selected for two-week
      community engagement activities. The key approaches used were: direct engagement
      with the public, participation in community activities, engagement with local
      primary health care services and distribution of information leaflets. Evaluation
      approach: Use of pre and post activities questionnaire and feedback meetings with
      key community members. RESULTS: Leaflets were distributed to a total of about
      18,000 addresses. Immediate result include: Increased donation, increased
      application for volunteering and increased referrals. Community involvement in
      end of life care waits to be evaluated. CONCLUSION: This is an on-going project.
      Early indications are that there has been improved awareness of the hospice
      services and interest in the hospice's activities. The project has also
      contributed to the hospice being included in the pathfinder charter community.

PMID- 25960506
TI  - PA20 Views on talking about death, dying and loss.
AB  - BACKGROUND: Societal barriers to open discussion of personal feelings and
      preferences relating to death may hinder planning for end of life and supporting
      people who are dying or bereaved. AIM: To explore views about talking about
      death, dying and loss. METHOD: Semi-structured interviews were conducted with 31
      people; age range 30 to 83 years. RESULTS: Making wills and communicating end of
      life wishes were considered very important; mostly for the sake of the family
      left behind. Participants also valued confidence to discuss other people's end of
      life wishes and support them appropriately if they were dying or bereaved. Many
      participants were very comfortable talking about their own death. Identified
      barrier to talking about end of life wishes included not wanting to upset others;
      others not listening; not being about to find an appropriate moment; not knowing
      enough about the options available; and fear of death, especially of the unknown.
      Financial costs were seen as a barrier to making a will. Participants talked of
      the importance of raising awareness of what death and dying involves; what end of
      life options available; and the importance of communication. Information on the
      process of normal grieving and how to support somebody who has been bereaved were
      also suggested. CONCLUSION: Being able to talk about end of life wishes and know
      how to support people who are dying or bereaved are important to many people, and
      they would welcome interventions to facilitate this at a societal level.

PMID- 25960507
TI  - PA21 Community participation in setting up palliative care clubs for chronically
      ill aids patients in lagos.
AB  - BACKGROUND: With the introduction of Highly Active Anti-retroviral Therapy, more
      HIV/AIDS patients live longer in our communities. AIM: This study was conducted
      to assess the willingness of people in Lagos to participate in setting up
      palliative care clubs for these patients. METHODOLOGY: Self administered
      questionnaires were completed by 261 respondents with age ranging from 21-61
      years. SPSS version 16 data editor was used to analyse data. Univariate odds
      ratios and 95% confidence intervals (95% CI) were used to evaluate the correlates
      of willingness to participate (WTP). RESULTS: A total of 62% of the respondents
      reported that they will be willing to participate in palliative care for the HIV
      patients. Higher willingness was associated with prior contact with higher
      education (OR = 1.13, 95% CI: 1.02-1.53), present employment (OR = 1.65, 95% CI:
      1.45-1.72) and a potential for financial incentives (OR = 1.59, 95% CI: 1.32
      1.77). Decreased WTP was associated with concerns about social stigmatisation (OR
      = 0.35, 95% CI: 0.13-0.71) and possibility of rejection by the patients (OR =
      0.83, 95% CI: 0.56-0.93). CONCLUSION: The high level of WTP indicates that such
      programmes would be better successful if organisers provide incentives as a part
      of the take-off of this program.

PMID- 25960508
TI  - PA22 The arts of connexion.
AB  - BACKGROUND: There is growing evidence that creative arts interventions improve
      perceived physical and mental. However, there is little research into arts
      interventions in relation to palliative care and the published studies in arts
      and health have focussed on visual arts with little attention to dance. AIM: A
      one year clinical audit was followed by a ten week pilot research study explored
      whether creative movement enabled people to feel more connected to themselves and
      each other, whether it supported the development of their collective voice and
      their ability to advocate for themselves and their peers. The service was offered
      on a group basis in Day Therapy and on a one-to-one basis for patients in the in
      patient unit. METHOD: Dance sessions were run weekly and evaluated at each
      session on a simple scale measuring connectedness to oneself and each other in
      the group, and the joy derived from attendance. RESULTS: Healthcare professionals
      reported that the sessions offered patients a chance to reconnect with the
      memories of their physicality, whilst also offering an experience that proferred
      joy, the opportunity to participate in a social group and focussed on sharing
      support. A patient's daughter who co-participated in a session reported "Two days
      before {my mother} died we had a movement session together; we have never felt so
      together as we did after that session". CONCLUSION: Whilst palliative care has
      long recognised the arts, there are benefits to be gained from collaborating and
      further research is needed to understand the nature and impact of creative
      interventions.

PMID- 25960509
TI  - PA23 Alternative method to providing palliative care where there are caregiver
      shortages.
AB  - BACKGROUND: Due to financial incapability and absence of manpower poor families
      often fail to carry their advanced cancer patients to the nodal centres. This
      pilot study will explore whether communication by mobile phone can lessen this
      burden. AIM: To identify and try to solve to the extent possible the main
      difficulties in giving palliative care to the terminal cancer patients of the
      area. METHOD: Initially a plan was generated regarding management of an advanced
      cancer patient in a nodal centre at District Head Quarters. Subsequently every
      two weeks, a trained social worker attached to the nodal centre will follow up
      and give necessary advice and emotional support to the patients and their
      families through their registered mobile phone number. Patient's family were also
      encouraged to communicate with the team by phone in case of fresh complaints and
      urgency. RESULTS: Since initiation, cancer patients were contacted by mobile
      phone every two weeks to enquire about their difficulties. In 76% of the
      situations, trained social workers could give necessary advice by phone regarding
      management of their physical symptoms. Moreover patient's family were really
      overwhelmed by the emotional support offered by the team over phone. Only 24% of
      cancer patients had to attend the nodal centre for expert advice from Palliative
      Care specialists. CONCLUSION: This novel approach helped In providing regular
      physical and emotional support to the patients and their families. In
      significantly reducing the financial and manpower problems of carrying patients
      to the nodal units. In improved quality of life of patients by continuous
      guidance. More and more team members can take help of this new strategy for
      better communication and uninterrupted care.

PMID- 25960510
TI  - PA24 A grounded theory analysis to explore the impact of group work as a method
      of service delivery by community matrons to support those living with multiple
      long-term conditions.
AB  - BACKGROUND: The role of the Community Matron was introduced in 2005 (DoH 2005a)
      to case-manage those patients deemed as very high intensity service users to
      prevent and reduce unscheduled admission to secondary care. Related studies on
      the effectiveness of managed care indicated the need to manage the demand of high
      service users who had multiple long-term conditions (LTCs). Little evidence
      exists as to how the role should be delivered to enhance disease self-management
      and levels of self-efficacy for the service users. AIM: Reviewing the role of
      Community Matrons in regard to their work with patients with multiple long-term
      conditions. METHODS: This qualitative participatory action research study
      explored the use of group work as a method of Community Matron intervention.
      Drawing on the theoretical underpinnings of Bandura's Social Learning Theory
      (1997), a social learning framework approach was adopt ed. Twenty nine
      participants with multiple long-term conditions were recruited. Within each
      intervention group there were 8-10 participants, led by a Community Matron
      working in both the researcher and practitioner role. RESULTS: Three main
      categories emerged that highlighted the process by which community matrons
      support patient groups; 1) comparison leading to re-motivation of the self
      through comparing others, 2) learning leading to enhanced self-management
      techniques through storytelling and understanding of each other's experiences and
      3) having ownership leading to the ownership of the self and of the groups they
      existed in. The emergent grounded theory revealed a Basic Social Process that
      conveyed the operation of three interrelated factors that helped to improve
      patients' self-efficacy and in turn their ability to engage effectively in their
      disease self-management. Through an action research approach the group work was
      led in a facilitative way, enabling the participants to work collaboratively with
      the researcher practitioner to choose and shape the care delivery. The core
      category of 'taking back the self-understanding the whole revealed the impact
      that this care delivery method had upon re-adjusting the balance of power between
      health professional and service users and its relationship to refreshing and
      improving disease self-management and self-efficacy. CONCLUSION: Community matron
      intervention using a model of group learning embedded in a social learning
      framework for those living with multiple long-term conditions can lead to more
      effective support, through improving self-efficacy and related self-management
      ability.

PMID- 25960511
TI  - PA25 Openness about death, dying and bereavement in fife - building on the skills
      and knowledge of our people.
AB  - BACKGROUND: A multiagency group was set up in 2011 to encourage a more open
      approach to death, dying and bereavement in Fife, linked to the Scottish
      Alliance, Good Life Good Death Good Grief. AIM: To encourage and facilitate a
      more open approach to death, dying and bereavement in Fife through raising
      awareness and encouraging people across society to consider how they can further
      this agenda themselves. METHOD: The group has organised two well attended Fife
      wide conferences, with a wide range of participants from different organisations
      and the public, an all day drop-in event at a shopping centre, and a cafe event.
      Group members also produced some brief and practical information about Wills,
      Powers of Attorney, Advance Directives, Funeral Planning and the death
      registration process. Both conferences drew on the knowledge and skills of the
      participants as members of society and encouraged them to have confidence to take
      forward the agenda in their own way. RESULTS: The most recent conference in
      November 2014 was very well received. A high proportion of attendees reported
      that they would take forward some actions themselves either at home, in their
      workplace or in their communities. CONCLUSION: The group's work complements Good
      Life Good Death Good Grief nationally and provides a local focus to enable wider
      conversations about openness about death, dying and bereavement in Fife and
      greater knowledge of practical information.

PMID- 25960512
TI  - PA26 Unmet needs and stress among caregivers of bedridden stroke patients in
      north kerala - a community based study.
AB  - BACKGROUND: In developing countries informal care by an unpaid relative is the
      most prevalent form of long-term care. Being bedridden consumes the victim and
      the caregiver physically, psychologically, socially and financially. In
      developing countries, strengthening support for family caregivers is essential to
      sustain long term health care system. Therefore unmet needs and burdens of family
      caregivers, including inadequate training, respite, and access to support
      programs should be studied and addressed. AIM: To study unmet needs of caregivers
      of stroke patients in the home settings. To study physical, psychological and
      social stress of these caregivers. METHOD:  STUDY DESIGN: Descriptive Study
      setting: Four rural panchayats, where home based care is given to bed ridden
      patients by the palliative team of our medical college. Sampling design:
      Convenience sampling study population: Care givers of bedridden stroke patients
      tool: A semi structured questionnaire RESULTS: Forty caregivers participated in
      the study. Their mean age was 51 years. Most were wives (15, 37.5%) and daughters
      (14, 35%). All belonged to low socioeconomic class. Unmet needs were lack of
      recreation (67%), inadequate sleep (67%), total responsibility (65%), illnesses
      (53%) and insufficient money (67%). Severe to moderate physical, psychological
      and social stress was seen in 90%, 87.5% and 70% of caregivers respectively.
      CONCLUSION: Services to be aimed primarily at informal caregivers may be designed
      to increase the level of knowledge and emotional support of caregivers, provide
      respite, or provide financial benefits as social schemes.

PMID- 25960513
TI  - PA27 Characteristics of hospitalizations of patients with cancer in brazil:
      analysis of data from 2008-2013.
AB  - BACKGROUND: Cancers figure among the leading causes of morbidity and mortality in
      Brazil, with approximately 576,000 new cases and around 200,000 cancer related
      deaths in 2013. According to the Brazilian National Oncological Policy (Decree
      GM/MS 2.439/2005) cancer control, like other chronic diseases, must involve all
      actions and health services available in the National Health System (SUS): health
      promotion, rehabilitation and palliative care, following the principles of the
      SUS: Universality, Equity and Completeness of health care. AIM: 1) Outline the
      profile of all cancer patients admitted to the hospitals of the Unified Health
      System (SUS) between 2008-2013; 2) Estimate the number of cancer patients with
      palliative care needs in the population. METHOD: The present methodology has a
      quantitative approach, with descriptive exploratory, retrospective and
      observational studies of hospitalised cancer patients. Data was collected from
      the hospital information system of the Unified Health System (SIH/SUS), obtained
      from the database of the Health Information Department of SUS (DATASUS). RESULTS:
      Between 2008 and 2013, there were almost 4 million hospitalizations (3,705, 024)
      of patients with cancer in Brazil. From this total 2,661,118 (71.8%) had
      malignant cancer and 286,566 (7.73%) resulted in hospital death. CONCLUSION:
      Estimating resources and specific parameters to structure and tailor palliative
      care assistance in countries whose health policies do not provide this mode, as
      the case of Brazil, has been a difficult task, considering the existing
      diversities between curative and palliative assistance and understanding
      regarding the combination of different types and criteria of care.

PMID- 25960514
TI  - PA28 Assessing physicians' perception of home based palliative care services in
      the beirut area.
AB  - BACKGROUND: The referral process in palliative care is influenced by the
      structure of the health care system and the understanding of the value of
      Palliative Care (PC) by healthcare practitioners and patients. Balsam-Lebanese
      Centre for Palliative Care is a non-governmental organisation that has been
      providing home-based palliative care services to patients in Greater Beirut since
      2010. Lebanon has a highly privatised fee-for-service health care system. In this
      setting, treating physicians may resist seeking palliative care services for
      their patients for fear of losing the patient. A lack of awareness regarding the
      added value of palliative care can also be detrimental to referral rates. We
      aimed to gain physician acceptance by providing high quality care, consistent
      communication, and education. AIM: To assess the perceptions of referring
      physicians towards our home-based palliative care service. METHODS: A sample of
      primary physicians whose patients have been under the care of Balsam will be
      interviewed to assess their perceptions of the quality and value of our service
      to their patients as well as the impact of the service on their practice. 10-15
      semi-structured interviews will be conducted transcribed and analysed
      thematically. RESULTS: Since the initiation of our in 2010, patient load has
      steadily increased. The pool of referring physicians has also increased from 3
      physicians in the first year to 58 physicians to date in 2014. In this study, we
      will share the findings from our qualitative study with referring physicians.
      CONCLUSION: Understanding the fears and concerns of referring physicians will
      guide further interventions and may improve referral rates.

PMID- 25960515
TI  - PA29 How has the natural death movement has been liftinig the lid on dying and
      funerals for 25 years?
AB  - BACKGROUND: 'Birth' was reclaimed through the natural child birth movement in the
      1970s and went on to inspire the origins of the natural death movement in the UK.
      The Natural Death Centre charity was launched in 1991 to reclaim death. However
      with any people's movement it responded to demand from the public into funerals.
      Until the last decade the funeral industry was a closed shop and the natural
      death movement has led consumer driven demand for change. The conference
      presentation will apply academic scrutiny to the history of the movement. AIM: As
      an anarchist movement the aims of the Natural Death Centre are fluid and ever
      evolving. METHOD: The conference presentation involves identifying key milestones
      in the natural death movement and the influences for change. Audio interviews
      with key leaders in the UK natural death movement will be transcribed and a
      content analysis will draw themes applied to the four concepts of a public health
      approach to palliative care. RESULTS: The results will allow an academic scrutiny
      to the UK natural death movement to act as a catalyst for change and creating new
      visions to share with the wider public health approach to palliative care
      community. CONCLUSION: The natural death movement is embracing and evolved away
      from traditional structures of health and palliative care. It complements more
      traditional methods for change.

PMID- 25960516
TI  - PA30 Why specialist community public health nurses should work in end of life
      care.
AB  - BACKGROUND: Overview of roots of public health nursing in UK. Specialist
      Community Public Health Nurses, formerly known as Health Visitors, have been
      responding to key health priorities in the United Kingdom for the past 150 years.
      The profession emerged in response to the appalling poverty and high infant
      mortality rates which characterised nineteenth century Victorian slums, and
      transformed itself in the twentieth century to provide family welfare "from the
      cradle to the grave", including social and mental health. Acheson's 1998
      definition of public health as "the organised application of resources to achieve
      the greatest health for the greatest number", dominated practice and preceded The
      New NHS: Modern and Dependable (1997) which put public health at the top of the
      agenda. The new approach meant crossing traditional boundaries and putting the
      'community' at the centre of healthcare through empowerment. Throughout these
      changes, the underpinning principles have remained the same, including the search
      for health needs, stimulation of awareness of health needs, influence on policies
      affecting health and facilitation of health-enhancing activities. AIM: To learn
      from other public health professionals. METHOD: Literature review. Specialist
      Community Public Health Nurses with an interest and experience in end of life
      care, can apply these same principles to the new public health approach to death
      and dying, searching for death and dying needs whilst stimulating an awareness.
      This would lead to exerting influence on policies affecting death and dying and
      facilitating health-enhancing activities. The public health approach is new to
      palliative and end of life care so it makes sense to learn from those
      professionals who have a long history of successfully responding, adapting to
      change, rising to contemporary challenges and harnessing opportunities. RESULTS:
      Understanding of how and when the public health agenda emerged. CONCLUSION: Other
      professionals have skills we need.

PMID- 25960517
TI  - PA31 Bridging the gap: strengthening relations between faith and hospice. a
      research project commissioned by hospice uk and together for short lives.
AB  - BACKGROUND: In an age where communities are becoming increasingly diverse how are
      Muslim communities (the second largest faith group in the UK) impacted by a lack
      of engagement with hospice care? How are hospices trying to meet the needs of
      British Muslim patients (and their relatives) who are coming towards the end of
      life? Statistics and reports evidence an ageing British Muslim population who
      will increasingly require the support and services of hospice care. This project
      will go some way in enabling a strong working relationship in order that Muslims
      can be confident, comfortable and capable of getting in touch with their local
      hospice and access crucial services such as adult/children's hospice care. It is
      also important that hospices are prepared to work with British Muslims
      holistically using a person-centred approach, and are equipped to do so. The
      building of these connexions will help to create a dynamic relationship between
      Muslims and hospices working towards a match between the needs of Muslim
      communities and the services offered by hospices. AIM: This project, combining
      both research and practice, will provide both a theoretical and practical
      understanding of where the challenges and opportunities lie in building a strong
      and vibrant relationship between hospices and British Muslim in East London.
      METHODS: A range of in depth interviews with hospice staff and community
      individuals/institutions Attending meetings/conferences where hospice care and
      diversity is explored Host Roundtable with palliative care and faith community
      experts Extracting, analysing and including feedback from the Community outreach
      events in London and Manchester RESULTS: Research in progress, to be continued
      April 2015. CONCLUSION: TBC.

PMID- 25960518
TI  - PA32 Family centred health care: a palliative care approach to engage communities
      to address the burden of hiv in tanzania abstract.
AB  - BACKGROUND: Tanzania is one of the countries most devastated by HIV and AIDS in
      the sub Saharan Africa. The Government of Tanzania has called for a community
      participation to address the burden of HIV in Tanzania(1) however the uptake of
      this call has been minimal. This paper intends to describe the role of Palliative
      Medicine in engaging communities to address burden of HIV in Tanzania. AIM: We
      aim to improve health outcomes of HIV+ children by engaging families through
      utilisation of palliative care principles in a low resource setting Method Single
      child with recurrent illness, multiple social spiritual and psychological
      problems was purposely selected from a pool of HIV+ children attending a PASADA
      HIV clinic and was offered care through palliative care approach. An
      interdisciplinary team of health providers was formed, goals of care were
      identified and care plan developed. Family members empowered with knowledge and
      skills to live with a HIV+ child and assigned specific role to ensure the boy's
      physical, psychological and spiritual needs are met. Through retrospective chart
      review, clinical meetings, counselling sessions with the child, family and
      providers information was gathered to enrich our understanding of the process.
      RESULTS: Goals of care were met: cleared infections, tested for HIV, resumed
      school, and family unified. Hundreds of children benefited from the experience
      generated and expansion of the approach was governed by community engagement.
      CONCLUSION: Families when empowered have much potentials that can reverse
      sufferings due to diseases through application of Palliative Care Principles in
      practice. REFERENCE: Tanzania Commission for AIDS. 2008 Annual Report.

PMID- 25960519
TI  - PA33 Reflections from the intersection of palliative care and design.
AB  - : This presentation is based on our reflections as two designers entering
      palliative care, one working with supportive environments for death and dying and
      one working with issues related to health-promoting palliative care. Death, dying
      and mourning are important universal conditions that raise existential thought
      and reflection. The focus of care is different here than in most other areas, as
      it is not about curing, and values go beyond medical perspectives. Thus, if we
      want to support meaningful experiences related to dying, it is necessary to look
      beyond institutional structures and disciplinary divisions. The practice of
      design has begun to move away from a primary concern with the commercial realm,
      to instead be used as a method to approach complexity to incrementally improve
      situations. A key aspect of this is to design with those concerned rather than
      for them. We argue that design related to contextual change requires an immersion
      within that context. An essential feature of design is making, and so, drawing on
      this disciplinary background, we iteratively try theories out, working towards
      minimising the gap between theory and practice. This approach, applied in a
      sensitive setting, has the potential to result in insights relevant in the
      particular situation, as well as offering transferable design methods. Convinced
      that the intersection of design and palliative care offers opportunities for both
      sectors, we will present concrete examples from our interdisciplinary research
      group, to talk about the opportunities and challenges of our work. 

PMID- 25960520
TI  - OA8 Caring for the family caregiver: working with volunteers to implement and
      improve a service to enable family caregivers to maintain their own wellbeing.
AB  - BACKGROUND: Family caregivers suffer physically, mentally, and spiritually.
      Community volunteers play an important role in supporting patients at the end of
      life or former caregivers in bereavement. However, there are no research reports
      of volunteer services focused on maintaining the wellbeing of end-of-life
      caregivers. AIM: To have volunteers, a hired volunteer coordinator, health care
      providers, and researchers implement and formatively evaluate a volunteer service
      to enable family caregivers to maintain their well being while providing care and
      subsequent bereavement. This presentation will focus on the volunteers' roles
      with the project as both agents of change to the service and as support for the
      caregivers. METHOD: A qualitative formative evaluation informed by Guba and
      Lincoln's Fourth Generation Evaluation (1989) participatory design was conducted.
      Data was collected through individual interviews, focus groups, participant
      observation during volunteer support meetings, and through volunteers' written
      reflections. RESULTS: Amongst the volunteers, volunteer coordinator, and
      principal investigator, there was mutual respect for and interest in learning
      about everyone's roles and experiences in the project. The experience was
      rewarding because they felt they helped the family caregiver and enjoyed
      developing and improving the service and working in a supportive team.
      Volunteers' challenges included being nervous for their first meeting with a
      caregiver, and frustration with some rules put in place to protect them (e.g. not
      helping the caregiver with direct care for the patient). CONCLUSION: Volunteers
      can be an effective part of the research team, while providing valuable support
      and encouragement for family caregivers to maintain their own wellbeing.

PMID- 25960521
TI  - OA9 Impact of medication safety in the palliative care home setting - the carers'
      perspectives abstract.
AB  - BACKGROUND: A Health Promoting Palliative Care philosophy, Kellehear (1999), was
      embraced to develop medication safety in the palliative care home setting in
      response tothe widespread informal practice of carers administering subcutaneous
      medications, especially in the last few days of life. Evaluations have
      demonstrated a legal and ethical framework for standardised practices enabling
      patients choices in place of care and death however a carer survey has been
      conducted to gain carer's perspectives. AIM: To ascertain how palliative carers
      feel about participating in administering subcutaneous medications in the home
      setting during end of life care. METHODS: Carers who accepted the invitation to
      participate, were surveyed by telephone 3-6 months post client death. Questions
      were provided pre-interview - 9 closed and 4 open-ended. RESULTS: 100% carers
      felt they worked in partnership with the team to manage symptoms. 100% believed
      training and support was easy to understand and inspired confidence. 81% felt
      they were able to give medications confidently- 19% exercised their right to not
      participate. Comments demonstrated the support, reassurance, and increased self
      worth of the carers developing a great sense of achievement. "Couldn't have been
      a happier time for me that he died in bed with his arm around me.....the
      grandkids were here.... we would all laugh together..." Negative aspects were
      around bereavement. CONCLUSION: Common themes demonstrated the importance of
      place of care an d death, pain control, access and timing of information and
      support, medication safety, exercising Choices, self-confidence, knowing and
      controlling care of dying and death, and bereavement care. REFERENCE: Kellehear
      A. Health promoting palliative care. Melbourne: Oxford University Press, 1999.

PMID- 25960522
TI  - WA10 Working in partnership with people with learning disabilities: academics and
      people with learning disabilities working together to disseminate the findings of
      a confidential inquiry into deaths of people with learning disabilities through
      film.
AB  - BACKGROUND: In England, between 2010-2013, a Confidential Inquiry into premature
      Deaths of People with Learning Disabilities was commissioned by the Department of
      Health. This took place in SW England led by Norah Fry Research Centre at Bristol
      University. Findings from the investigations into 247 deaths included that men
      with learning disabilities die, on average 13 years sooner and women, on average
      20 years sooner, than the general population. Over 1/3 (37%) were found to be
      avoidable, being amenable to good quality healthcare. A number of key
      recommendations were made which required understanding by a range of audiences
      including people with learning disabilities and their carers. AIM: This workshop
      will demonstrate how academics can work with actors with learning disabilities to
      disseminate research findings about a sensitive subject in a thought provoking
      and accessible way. METHODS: Academics worked with the MISFITs theatre company to
      make a DVD about the findings and recommendations of the Confidential Inquiry.
      RESULTS: The DVD presents the findings of the Confidential Inquiry through the
      stories of John, Bill, Karen and Emily. It powerfully illustrates the importance
      of diagnosing and treating illness of people with learning disabilities in a
      timely and appropriate manner and highlights the measures that could be taken to
      reduce premature deaths in this population. CONCLUSION: The session provides an
      example of how the voices of people with learning disabilities can communicate
      research messages effectively to people with learning disabilities, health and
      social care practitioners and others who support the learning disability
      population.

PMID- 25960523
TI  - OA11 Public health and hospices: what is really possible?
AB  - INTRODUCTION: Whilst a growing number of hospices are proactively engaging in the
      public health agenda, questions remain about whether this is an approach that
      hospices can adopt successfully. (Sallnow et al . 2014). The experience of St
      Christopher's in the development of its social hub (The Anniversary Centre)
      offers insights into the challenges and how these are best addressed. BACKGROUND:
      The Anniversary Centre was established to provide a more open and flexible
      approach to end of life care and to challenge and change public attitudes towards
      death and dying. It sought, also, to contest an existing culture of care,
      shifting from professional management of problems to one in which people take a
      lead in their own care and wellbeing. METHODS: A review of the progress of the
      Centre in achieving these aims has been undertaken five years after its
      establishment. Questions focus on: The degree to which the centre has engaged
      more of the local communities How much its users are able to determine their own
      priorities, care and wellbeing through attendance at the centre What evidence of
      a public health approach exists in the support it provides. RESULTS: The Centre
      offers a new and alternative way of supporting people living with a life
      threatening condition. Although successes have been achieved, organisational and
      historical cultural barriers continue to limit progress. CONCLUSION: Hospice
      culture can prohibit public health approaches to palliative care. However,
      related innovation is possible when clear values and stories are shared,
      champions are identified and professional assumptions are challenged. REFERENCE:
      Sallnow L, Paul S. Understanding community engagement in end-of-life care:
      developing conceptual clarity. Crit Public Health 2015;25(2):231-8.

PMID- 25960524
TI  - OA12 When grief and work collide.
AB  - BACKGROUND: There is a significant price to pay for organisations that fail to
      take seriously the challenges involved in supporting grieving employees in the
      workplace, including loss of productivity, sickness absence, and low morale. The
      purpose of this study was to look at how social service organisations implement
      their bereavement policies and support bereaved staff. AIM: The study aimed to
      raise awareness of current issues and practices in the implementation of
      bereavement policies and the management and support of grieving employees on
      their return to work. METHODS: A generic qualitative method was used and
      recruitment of six participants from social service organisations within New
      Zealand was undertaken. Non-probability purposive sampling was used. Data
      collection was via email interviews. RESULTS: While New Zealand employees are
      legally entitled to three days paid bereavement leave, how flexible and
      supportive employers were willing to be beyond that varied. Participants felt out
      of their depth in dealing with grieving employees and lack of training around
      grief and loss meant a heavy reliance on external sources of support. The study
      also exposed a possible lack of understanding in relation to cultural mourning
      rituals. CONCLUSION: This study uncovered several areas of concern relating to
      organisational attitudes towards grieving employees and their ability to
      adequately support bereaved staff on their return to work. It poses the question
      for future research as to whether organisations can afford not to care and serves
      as a springboard for examining the detrimental consequences of neglecting the
      realities of loss.

PMID- 25960525
TI  - OA13 Developing sustainable community partnerships to provide ongoing bereavement
      support.
AB  - BACKGROUND: This project was developed within an urban home-based palliative care
      service. It commenced in response to the recognition that acutely grieving people
      needed long term, broad-based community support, and the need for death education
      in the community. AIM: It was hoped that bereavement support groups could be
      relocated from a clinical environment to the community, so that bereaved people
      could access support in their neighbourhoods, develop supportive local connexions
      and be introduced to a variety of resources. This would result in developing
      community partnerships, provide death education, assist in normalising death,
      dying and grief and in redressing the 'death taboo' in society. METHOD: Once the
      concept was approved by the community palliative care service, local community
      centres were identified, connexions made and discussions held regarding building
      partnerships to provide bereavement support. Two community centres responded
      enthusiastically and partnerships have slowly developed. RESULTS: After 2 years,
      feedback from bereaved carers has consistently endorsed the move to community
      centres. Staff at one centre have now offered administrative support, requested
      'open' grief support groups and grief education sessions. Staff from the other
      centre have requested a joint memorial service and training in loss and grief for
      staff. CONCLUSION: Developing sustainable community partnerships takes time and
      has required Significant evolutional learning. In particular, it must not become
      dependent on the specific personnel driving the project and there is a need to
      develop further protocols and 'embed' the practice. This is an organic process
      which will continue to grow in response to further development of the
      partnership.

PMID- 25960526
TI  - OA14 Good life, good death, good grief: changing scottish culture.
AB  - BACKGROUND: Social harms are caused in Scotland because of a cultural reluctance
      to be open about death, dying and bereavement, and there is growing recognition
      of the importance of promoting culture change relating to these issues. AIM: Good
      Life, Good Death, Good Grief (GLGDGG) was established to make Scotland a place
      where there is more openness about death, dying and bereavement. METHODS: Led and
      supported by the Scottish Partnership for Palliative Care, GLGDGG follows an
      "assets-based" approach-engaging, supporting and enhancing the assets of others.
      RESULTS: GLGDGG has: assisted in mobilising the assets of communities (eg through
      establishing small grants schemes and focal points of activity like To Absent
      Friends.) influenced policy (eg key messages incorporated within significant
      publications) found innovative ways of achieving impact on minimal resources (eg
      Death on the Fringe) CONCLUSION: A national alliance to encourage and guide
      activity is helpful in engaging communities and shaping policy.

PMID- 25960527
TI  - WA15 To absent friends: a people's festival of storytelling and remembrance.
AB  - BACKGROUND: Communities play a key role in supporting members through difficult
      times, yet bereaved individuals often experience social isolation. Palliative
      care services should make efforts to develop community capacity to support
      bereaved people. Rituals of remembrance build solidarity. There are indications
      that many people would like to talk more openly about dead loved ones but are
      restricted by cultural norms. AIM: To create a time of year when remembering dead
      loved ones is socially accepted and supported within mainstream culture. METHODS:
      To Absent Friends, a People's Festival of Storytelling and Remembrance was held
      across Scotland, 1-7 November 2014. Efforts were made to promote the festival,
      but not to control the form of people's participation. RESULTS: A wide variety of
      events took place including community-based activities and high profile
      participation, for example from the Royal Scottish National Orchestra quartet,
      and the Scottish Rugby Union. CONCLUSION: A public festival in celebration and
      remembrance of dead loved ones has resonance for many people in Scotland and
      should grow in future years.

PMID- 25960528
TI  - WA16 If my body is ill, who am i? pain relief through expression of whole self.
AB  - BACKGROUND: People rely on mobility and bodily capacity to define who they are.
      Little has been written about how bodily incapacity towards the end of life
      affects a person's self-concept. Expressive Movement Therapy (EMT) (also called
      Dance Movement Psychotherapy) enables people to use creative movement/gestures to
      express themselves physically, emotionally, socially and spiritually. This is the
      first known research about EMT in palliative care in the UK. AIM: To explore
      clients' experiences of EMT in a day hospice setting. METHODS: A
      phenomenological/case study approach explored four clients' experiences of EMT in
      depth. RESULTS: Participants used EMT to express how their ill bodies had become
      obstacles to defining who they are, causing a complex interaction between
      physical incapacity and emotional, social and spiritual pain. EMT released
      tension by enabling participants to grieve over these losses of self, and to re
      integrate with their estranged bodies to express themselves as "me completely".
      CONCLUSION: This research provides a new understanding of the concept of 'total
      pain'. It links physical suffering to emotional, social, spiritual pain by
      showing that bodily incapacity prevents people from expressing their sense of
      whole self. EMT helps relieve this pain by offering people accessible, creative
      ways to reconnect with their ill, estranged bodies to express themselves as an
      integrated complete person. The community needs to adopt a holistic approach,
      which does not just focus on parts of the body, but recognises the importance of
      helping people sustain their self-narrative as a whole person in all dimensions
      of their lives.

PMID- 25960529
TI  - OA17 Compassionate communities: engaging with communities to support patients at
      end of life: a birmingham st. mary's hospice lived experience.
AB  - BACKGROUND: Researchers carrying out a rebranding exercise for us in 2006 found
      that people from Black Asian and other Minority Ethnic (BAME) communities did not
      respond to their survey. This appeared to support anecdotal evidence from staff
      suggesting that the number of BAME patients accessing our services did not
      reflect the real need. AIM: To increase access to Hospice Care services for
      people from BAME communities. METHODS: From April to July 2007 we used
      qualitative methods to carry out an exploratory study, to identify barriers to
      hospice care for patients from BAME communities. Currently we use community
      development methods to raise awareness of hospice services among BAME communities
      in Birmingham and Sandwell; while offering training and cultural/spiritual broker
      services to clinicians increasing their understanding of patients and families
      from these communities. RESULTS: There was no information about Hospice care
      services among people from BAME communities. Many people from BAME communities
      belong to cultural or spiritual groups whose members support each other during
      times of celebration, illness, death and bereavement. They refer to this support
      as 'our way of life'. Death, dying, and cancer are taboo subjects. CONCLUSION: In
      2009 we set up the Compassionate Communities Project (CCP) within our Reaching
      People Programme (RPP) to increase access to our services for people from BAME
      communities. CCP enables community groups and service providers to work together
      in end of life. Representatives from BAME communities help train clinicians on
      supporting people from their communities in end of life.

PMID- 25960530
TI  - OA18 Population based end of life care - meeting the challenge of the ageing
      population.
AB  - BACKGROUND: The key challenge for most developed countries is meeting the needs
      of our ageing population, in particular, those nearing the end of their lives -
      population-based end-of-life care. Building on a public health approach to meet
      needs of an area-wide population, and a practical approach of enabling generalist
      frontline staff care for all people in a variety of settings using the GSF
      Quality Improvement Programmes, we describe progress in a few GSF Cross-Boundary
      Care Foundation Sites taking a population-based view to meet the challenges of
      the ageing population. AIMS: Taking a whole-system view, we explore ways to
      ensure all people receive quality care towards the final stages of life in line
      with their needs and wishes in a way that is cost-effective, responsive and
      compassionate. Expanding concepts of palliative/end-of-life care to include care
      for people with long-term conditions, dementia, and frailty. METHODS: We describe
      practical progress in a number of GSF XBC Sites, enabling generalist frontline
      staff including: Identifying and prioritising people earlier Reducing 'diagnostic
      apartheid' Enabling more to live well and die well in the place and manner of
      their choosing Encouraging integrated person-centred care, reducing inappropriate
      over-Hospitalisation and prevention of over - medicalising. RESULTS: Use of GSF
      in various settings to enable generalist frontline staff is described, with key
      outcome measures and evaluations in the UK, and internationally. CONCLUSION: As
      the population ages, population-based end of life care will be one of the most
      significant developments to meet the challenges for a fit-for-purpose health
      service of the future.

PMID- 25960531
TI  - OA19 Can oral history in palliative care influence the well-being of participants
      and the bereaved?
AB  - BACKGROUND: Oral history is the audio recording of unique life experience.
      Participants are involved in producing their own life histories, in their own
      voice, with no medical agenda. Oral history in palliative care began as a service
      in Sheffield in 2007 with Sheffield Hospitals Charity. In 2012 Macmillan Cancer
      Support piloted five further services in the North of England and Northern
      Ireland. AIM: To assess the impact of recording an oral history in palliative
      care and to understand how the recording is received by family in bereavement.
      METHODS: The study conducted semi-structured interviews with people associated
      with oral history in Sheffield. Thirty two interviews were carried out with 10
      patients; 9 bereaved family members; 6 health and social care professional; 7
      bereavement support volunteers. RESULTS: People who had made recordings said that
      it was an enjoyable experience and that creating a family record was important to
      them. Bereaved family and friends stressed that having a voice recording was
      important for them and a comfort to listen to. The process of making the
      recording brought families together to share memories and find connexions and
      meanings. CONCLUSION: Oral history interviewees, their family, bereavement
      volunteers and health professionals were enthusiastic about oral history. The
      research highlighted that creating a personal voice legacy can be an act of
      caring by the dying person, to help families subsequently cope with loss. The
      oral history process is seen as positive for the well-being of individuals in
      palliative care and bereaved family and friends.

PMID- 25960532
TI  - OA20 The positioning of family, friends, community, and service providers in
      support networks for caring at end-of-life: a social network analysis.
AB  - BACKGROUND: Although there is ample evidence of the risk to carers from the
      burden of caring, there is also evidence that a caring network can relieve the
      burden on the principal carer, strengthen community relationships, and increase
      'Death Literacy' in the community. There is often an assumption that, in caring
      networks, family and service providers are central and friends and community are
      marginal. We examined whether this is the case in practice using SNA. AIM: To
      identify the relative positioning of family, friends, community, and service
      providers in caring networks. METHODS: In interviews with carers (N = 23) and
      focus groups with caring networks (N = 13) participants were asked to list the
      people in the caring network and rate the strength of their relationships to them
      (0 no relationship to 3 strong relationship). SNA in UCInet was used to map the
      networks, examine density (number and strength of relationships) across time
      (when caring began to the present) and across relationship types (family,
      friends, community, and service providers) supplemented by qualitative data.
      RESULTS: The analysis revealed significant increases in the density of the
      networks over time. The density of relationships with friends was similar to that
      other family. Community and service providers had significantly lower density.
      Qualitative analysis revealed that often service providers were not seen as part
      of the networks. CONCLUSION: To avoid carer burnout, it is important not to make
      assumptions about where carers obtain support but work with each carer to
      mobilise any support that is available.

PMID- 25960533
TI  - OA21 The power to choose: developing community capacity to provide palliative
      care in four first nations communities in canada.
AB  - BACKGROUND: First Nations people in Canada are ageing with a high burden of
      chronic, progressive, and life-limiting illness. The majority now die in urban
      hospitals or long term care homes far away from family and culture. Today, First
      Nations community leaders are working to build local community capacity to
      support people and their families who choose to die at home. AIM: This
      presentation describes a five year participatory action research project that has
      enhanced local palliative care capacity in four First Nations communities using
      innovative strategies for collaboration, education, and advocacy
      (www.eolfn.lakeheadu.ca). METHODS: The process of community capacity development
      was locally driven and controlled. A local leader and advisory committee
      implemented a palliative care community assessment that identified resources and
      needs for community awareness, health provider education, service development and
      improved partnerships with external health care providers (physicians, hospitals
      etc) providing care to community members. Innovative strategies to address these
      needs were developed, implemented and evaluated. RESULTS: If services and
      community supports were available, 87% of the FN community participants would
      prefer to die at home. Each of the four participating FN communities developed a
      unique palliative care program model responsive to community culture and context.
      Culturally appropriate videos and print resources for education and community
      development were created to share internationally. CONCLUSION: First Nations
      communities have the desire and capacity to care for community members to the end
      of their lives. Community development and advocacy are required to support First
      Nations in addressing existing barriers and gaps in education, policy and service
      delivery.

PMID- 25960534
TI  - WA22 "it's hard to watch people die for a living": embedding the palliative
      approach into the organisational culture of long term care homes using
      participatory action research.
AB  - BACKGROUND: Long term care homes (LTC) in Canada have become a major location of
      death with 20% or more residents dying each year. Given the increasing age and
      frailty of residents, this is soon expected to increase to 40%. LTC has struggled
      to incorporate care of the dying into their day to day practice and culture
      because death is often absent from formalised policy and protocols. AIM: This
      workshop will share resources created during a 5 year participatory action
      research project in Ontario, Canada that aimed to improve the quality of life of
      people who were dying in long term care homes. METHODS: Through staff
      participation and empowerment, a process of organisational capacity development
      was undertaken. An extensive needs assessment was followed by creating an
      interprofessional palliative care resource team within each home. This team
      assessed the assets and gaps in their home and guided development of education,
      policy and clinical practices to address needs. Community partners with expertise
      in palliative care were engaged to support staff. RESULTS: A framework for
      palliative care in LTC integrates the palliative approach into the residents'
      journey from admission to death. Resources for organisational change were
      developed and organised into a toolkit that is unique to the LTC setting and
      context, and can be accessed at www.palliativealliance.ca CONCLUSION: The Quality
      Palliative Care in Long term Care Toolkit is the first of its kind in Canada. The
      toolkit can guide LTC management and staff through a process of culture change to
      incorporate a palliative approach to care.

PMID- 25960535
TI  - WA23 Research methodology workshop.
AB  - BACKGROUND: Public health approaches to end of life are a relatively recent
      development; hence research methodology in this area is also being developed.
      AIM: A workshop for practitioners and researchers describing methodologies used
      by an end of life public health programme to develop and test interventions and
      assess the needs and potential for success of further work. METHODS: During the
      workshop we will describe the methodologies used in a programme which aimed to
      reframe death and loss as social event and additionally included participatory
      approaches and engaging communities. Mixed methods approaches of direct
      observational methods, longitudinal questionnaire surveys to determine both
      immediate and sustained effectiveness of interventions and also semi-structured
      interviews will be described. The workshop will present this work, reflect on
      other methodologies that could be used; discuss what worked well and not so well,
      and encourage discussion of other people's research in this area and further
      development. The importance of retention and follow up of participants will be
      discussed as will issues regarding qualitative interviewing in this area and
      further interventions regarding how participants can be encouraged to share their
      thoughts and ideas re public health and palliative care thereby helping to shape
      the practical and research agenda. The subject and value of evaluation as opposed
      to research will also be discussed. CONCLUSION: At the end of this workshop,
      researchers and practitioners wishing to evaluate and research their programmes
      will have gained a better understanding of the theoretical and practical
      applications of research and evaluation.

PMID- 25960536
TI  - OA24 Support for terminally-ill cancer patients: perceptions of religious leaders
      about end-of-life spiritual care in lagos, nigeria.
AB  - BACKGROUND: Religious leaders are well respected in most Nigerian communities and
      are often called in to provide support for terminally-ill patients. Many Nigeria
      communities still view cancer as a stigmatised disease. AIM: This study sought to
      elicit the perceptions of Christian and Islamic religious leaders and explore
      problems associated with their involvement in end-of-life care for cancer
      patients. METHODOLOGY: Participants were recruited among 114 religious leaders.
      Four focus group discussion sessions were then conducted with open-ended
      questions on previous involvement in end-of-life care of cancer patients and
      whether they would like to do more. There were thirty (30) willing participants
      in all. The discussions were audiotaped, transcribed and coded using the NUDIST
      software. RESULTS: Ninety of the respondents (62%) would not be involved in end
      of-life care. This is because of the fear of peer pressure. The responses could
      be classified under three major themes were identified: (1) Care supposed to be
      provided by all religious leaders (2) End-of-Life care in institutions are safer
      (3) End-of-Life care consumes time. Statements made by respondents include "I
      will fall out with many if I am found ministering to dying patients". CONCLUSION:
      We observe that peer pressure played an important role in the acceptability of
      end-of-life activities in this group. This could be used in the positive light in
      designing interventions.

PMID- 25960537
TI  - OA25 The namaste care programme can enrich quality of life for people with
      advanced dementia and those who care for them without additional resources.
AB  - BACKGROUND: In the United Kingdom most people with advanced dementia die in care
      homes. Families judge quality of life and end of life as poor. The Namaste Care
      programme integrates compassionate nursing care with meaningful activities for
      people with advanced dementia at the end of their lives. Namaste uses sensory
      input, touch, music, massage, colour, tastes and scents, to connect with people
      with advanced dementia. No extra staff or expensive equipment are required. AIM:
      To establish whether Namaste Care could be implemented in United Kingdom care
      homes, and whether Namaste can enrich the quality of life of care home residents,
      families and staff without requiring additional resources. METHOD: We
      collaborated in an action research study with five care homes to implement the
      Namaste Care Programme. We collected quantitative data about residents using the
      Neuropsychiatric Inventory (NPI) and Doloplus 2 pain assessment scale as primary
      outcome measures. Qualitative data was gathered from focus groups with care staff
      and families and interviews with managers. RESULTS: 37 residents were recruited
      to the study. In care homes with good pain management, Namaste Care was
      significantly effective in reducing behavioural symptom severity over time.
      Families, care staff and managers welcomed Namaste. Extra staff and financial
      resources were not needed to implement the programme. CONCLUSION: Where there was
      good leadership and adequate clinical care, the Namaste Care programme supported
      compassionate care and enhanced quality of life for people with advanced dementia
      at the end of their lives. No additional resources were required.

PMID- 25960538
TI  - OA26 How inclusive partnership working influences local policy and practice: the
      case of the end of life partnership.
AB  - : Ageing, death, dying and loss are universal issues that have a range of health,
      wellbeing, financial and socio-economic costs for society. AIM: The End of Life
      Partnership (EoLP) is a charitable collaborative in Cheshire, which aims to
      transform end of life experience and care, by working with a wide range partners
      from the public, private and third sectors and by engaging individuals, families
      and communities. METHOD: Launched in April 2014, the EoLP merged three existing
      programmes focussing on public health, education and service development and
      added an additional research focus. There are now four dedicated departments:
      Public Health and Wellbeing; Research, Evaluation and Technology; Service
      Development; Education and Practice Development. In October 2014 a Dementia work
      stream was added. The work of The EoLP is shaped, overseen and monitored by a
      Strategic Partnership Executive, with representation from key local stakeholders
      and a board of trustees. The EoLP meets national objectives and delivers on local
      priorities agreed with stakeholders, including patients and the public. This is
      strengthened through a dedicated Cheshire Living Well, Dying Well Partnership to
      enable community voices to be heard. RESULTS: Significant milestones have already
      been realised as a partnership collaborative. For example, response to the
      national review of the Liverpool Care Pathway incorporated development of a local
      care plan with stakeholders, educational strategy to ensure effective roll-out,
      public consultation and work to measure impact. CONCLUSION: The EoLP works to
      influence and shape policy and practice at a local, regional, national and
      international level.

PMID- 25960539
TI  - OA27 Rural palliative care for low resource settings among marginalised
      communities in the south indian state of tamilnadu - a new venture with two and a
      half years of outcome.
AB  - BACKGROUND: India with a total of 1.27 Billion (2014) population and over 73% of
      them are living in rural areas. Cancer remaining as the second cause of death in
      rural community and at any given time over 4 million cancer cases are living in
      our country and most of them are diagnosed at their advanced stages and suffering
      with intractable pain and 'total sufferings'. At present, time available for
      palliative care services is less than 1% for the needy, it is mostly spread out
      around the urban areas leaving the remaining 73% of rural sufferers in lack of
      availability, accessibility, acceptability and affordability. AIM: To identify
      the need for palliative care, in a particular Block of the district, and provide
      home based total care. METHOD: Selection of 'Andanallur' village block with a
      population of nearly 100,000. Sensitisation of the health care staff, village
      members, self help groups and schools and through the Information, educative and
      communication methods. Conduction of a primary survey to identify the needy
      Examination and short listing cases for home based Palliative care Home based
      palliative care RESULTS: The project was started in 2011 January and 156 cases
      short listed; 121 cases started with home care and 52 cases had passed away, 8
      cases were given end of life care. CONCLUSION: Palliative care reaching the
      sufferers directly Reaching the unreachable and under-privileged Need based
      'total care' at their door steps Empowering and training the family members.

PMID- 25960540
TI  - OA28 At the clinical shores - palliative care volunteers and population health in
      new south wales (NSW).
AB  - BACKGROUND: In October 2014 a detailed mapping study of volunteers in palliative
      care services in NSW was undertaken for the first time. This presentation will
      provide a thematic analysis of the initial findings. AIMS: The aim of this study
      was to provide a thematic analysis of the occupational terrain of palliative care
      volunteers across NSW as part of a project to develop the capacity of palliative
      care volunteer services and to raise public awareness of their work. METHOD: A
      total of 44 Volunteer Coordinators, clinicians and other health service staff
      were surveyed across 38 services mostly by telephone and face-to-face meetings
      using a 21 question survey which measured quantitative and qualitative data.
      RESULTS: The survey clarified the number and distribution of the 38 palliative
      care services, 1,242 volunteers and 22 full-time-equivalent volunteer
      coordinators in NSW. Data included comments made by participants in the survey,
      and thematic analysis reveals that the palliative care volunteers are constructed
      as neither exclusively clinical nor non-clinical in nature. CONCLUSION:
      Palliative care volunteers metaphorically stand at the shores of the clinical
      domains, interacting collegially with the clinician but identifying with the
      public and acting to guide people ashore and through the expert landscape. The
      report concludes that given the emergent nature of palliative care practice there
      are precedents for the inclusion of palliative care volunteers more extensively
      within communities of practice at strategic, policy and operational contexts, but
      this might actually do a disservice to the unique function of volunteers as coast
      watchers.

PMID- 25960541
TI  - WA29 "we are all one" compassionate cities "a global community joined for care".
AB  - BACKGROUND: The NewHealth Foundation, a Spanish non-for-profit organisation, is
      leading the project Compassionate Cities. "We are all one". The project aims to
      involve citizens in creating communities of care to help people at the end of
      life phase. AIM: To design and develop a practical model to engage communities in
      the process of improving the quality of public palliative care. To empower key
      advocates of end-of-life care. To evaluate communities' interventions, their
      feasibility and impact in terms of shared benefit for stakeholders. METHODS:
      Identification and recruitment of key advocates of care. Design of an innovative
      model of compassionate cities. Define community of care activities through a
      triple-dimension methodology: [To Want - To Know - To Do]. RESULTS: An innovative
      model has been developed: The Collaborating Centre (schools, colleges, cultural
      centres, professional's associations, patient's associations, NGOs, brotherhoods,
      churches, etc.) organises the agenda of training events and promotes networking.
      Citizens set up "care clusters", becoming available to provide care. The
      Beneficiaries Centres (hospices, nursing homes, residential centres, patient
      organisations, hospitals, health and social care centres, etc.) contact the
      clusters when care needs of patients are identified. The palliative care
      specialist supports Compassionate Communities training and refer patients to
      clusters. Local Government (also a collaborating centre) encourages awareness
      campaigns and provides institutional support. Companies collaborate in promoting
      and funding the project. Six cities in Spain and 3 in Colombia have already been
      selected and local initiatives are already being promoted (more results to be
      provided at the Congress). CONCLUSION: This model supports people to become the
      real co-producers of services, as they know which services best respond to their
      needs.

PMID- 25960542
TI  - A Sporozoite- and Liver Stage-expressed Tryptophan-rich Protein Plays an
      Auxiliary Role in Plasmodium Liver Stage Development and Is a Potential Vaccine
      Candidate.
AB  - The liver stages of the malaria parasite are clinically silent and constitute
      ideal targets for causal prophylactic drugs and vaccines. Cellular and molecular
      events responsible for liver stage development are poorly characterized. Here, we
      show that sporozoite, liver stage tryptophan-rich protein (SLTRiP) forms large
      multimers. Mice immunized with a purified recombinant SLTRiP protein gave high
      antibody titers in both inbred and outbred mice. Immunized mice showed highly
      significant levels of protection upon challenge with sporozoites and exhibited
      10,000-fold fewer parasite 18S-rRNA copy numbers in their livers. The protection
      offered by immunization with SLTRiP came mainly from T-cells, and antibodies had
      little role to play despite their high titers. Immunofluorescence assays showed
      that SLTRiP is expressed in the sporozoite and early to late liver stages of
      malaria parasites. SLTRiP protein is exported to the cytosol of infected host
      cells during the early hours of parasite infection. Parasites deficient in SLTRiP
      were moderately defective in liver stage parasite development. A transcriptome
      profile of SLTRiP-deficient parasite-infected hepatocytes highlighted that SLTRiP
      interferes with multiple pathways in the host cell. We have demonstrated a role
      for SLTRiP in sporozoites and the liver stage of malaria parasites. 

PMID- 25960543
TI  - Wound healing and longevity: lessons from long-lived alphaMUPA mice.
AB  - Does the longevity phenotype offer an advantage in wound healing (WH)? In an
      attempt to answer this question, we explored skin wound healing in the long-lived
      transgenic alphaMUPA mice, a unique model of genetically extended life span.
      These mice spontaneously eat less, preserve their body mass, are more resistant
      to spontaneous and induced tumorigenesis and live longer, thus greatly mimicking
      the effects of caloric restriction (CR). We found that alphaMUPA mice showed a
      much slower age-related decline in the rate of WH than their wild-type
      counterparts (FVB/N). After full closure of the wound, gene expression in the
      skin of old alphaMUPA mice returned close to basal levels. In contrast, old FVB/N
      mice still exhibited significant upregulation of genes associated with growth
      promoting pathways, apoptosis and cell-cell/cell-extra cellular matrix
      interaction, indicating an ongoing tissue remodeling or an inability to properly
      shut down the repair process. It appears that the CR-like longevity phenotype is
      associated with more balanced and efficient WH mechanisms in old age, which could
      ensure a long-term survival advantage. 

PMID- 25960545
TI  - Ultrastructure of the spermatozoon of the trematode Notocotylus noyeri (Digenea:
      Notocotylidae), a parasite of Microtus arvalis (Rodentia: Cricetidae).
AB  - In the present paper, we describe the ultrastructure of the spermatozoon of the
      notocotylid Notocotylus noyeri (Joyeux, 1922) by means of transmission electron
      microscopy. The mature spermatozoon of N. noyeri exhibits the general pattern
      described in the majority of digeneans: two axonemes of the 9 + "1" pattern of
      the Trepaxonemata, nucleus, mitochondria, parallel cortical microtubules, spine
      like bodies and ornamentation of the plasma membrane. The glycogenic nature of
      the electron-dense granules was evidenced applying the test of Thiery. The
      ultrastructural features of the spermatozoon of N. noyeri present some
      differences in relation to those of the Pronocephalidea described until now, but
      confirm a general pattern for the Notocotylidae, namely a spermatozoon with two
      mitochondria and an anterior region with ornamentation of the plasma membrane
      associated with spine-like bodies. The posterior extremity of the spermatozoon
      exhibits only some microtubules after the disorganisation of the second axoneme.
      The present study confirms that some ultrastructural characters of the sperm cell
      such as the presence or absence of lateral expansions, the number of mitochondria
      and the morphology of both anterior and posterior spermatozoon extremities are
      useful for phylogenetic purposes within the Pronocephaloidea. Thus, unlike
      notocotylids, pronocephalids exhibit external ornamentation and a lateral
      expansion in the anterior spermatozoon region. Moreover, notocotylid spermatozoa
      present two mitochondria, whereas pronocephalid spermatozoa exhibit a single
      mitochondrion. Finally, pronocephalids are characterised by a type 2 posterior
      spermatozoon extremity, whereas notocotylids exhibit a type 3 posterior
      spermatozoon extremity. 

PMID- 25960544
TI  - Connexin 43 expression is associated with increased malignancy in prostate cancer
      cell lines and functions to promote migration.
AB  - Impaired expression of connexins, the gap junction subunits that facilitate
      direct cell-cell communication, have been implicated in prostate cancer growth.
      To elucidate the crucial role of connexins in prostate cancer progression, we
      performed a systematic quantitative RT-PCR screening of connexin expression in
      four representative prostate cancer cell lines across the spectrum of malignancy.
      Transcripts of several connexin subunits were detected in all four cell lines,
      and connexin 43 (Cx43) showed marked elevation at both RNA and protein levels in
      cells with increased metastatic potential. Analysis of gap-junction-mediated
      intercellular communication revealed homocellular coupling in PC-3 cells, which
      had the highest C x 43 expression, with minimal coupling in LNCaP cells where C x
      43 expression was very low. Treatment with the gap junction inhibitor
      carbenoxolone or connexin mimetic peptide ACT-1 did not impair cell growth,
      suggesting that growth is independent of functional gap junctions. PC-3 cells
      with C x 43 expression reduced by shRNA showed decreased migration in monolayer
      wound healing assay, as well as decreased transwell invasion capacities when
      compared to control cells expressing non-targeting shRNA. These results, together
      with the correlation between C x 43 expression levels and the metastatic capacity
      of the cell lines, suggest a role of C x 43 in prostate cancer invasion and
      metastasis.

PMID- 25960546
TI  - Molecular characterisation of Cryptosporidium (Apicomplexa) in children and
      cattle in Romania.
AB  - To investigate the transmission of species of Cryptosporidium Tyzzer, 1907 in
      Timis County, Romania, 48 isolates of Cryptosporidium coccidia from 11 children,
      29 calves and eight pigs were characterised by molecular analysis of two loci
      (SSU rRNA and 60-kDa glycoprotein gene). Overall, 22 isolates were amplified and
      sequence analyses revealed that all isolates were Cryptosporidium parvum Tyzzer,
      1912. Two subtype families were identified, IIa and IId. Subtype IIdA22G1 (n = 4)
      was the single C. parvum subtype found in children. Subtypes found in calves
      included IIdA27G1 (n = 8), a novel subtype, IIdA25G1 (n = 5), IIdA22G1 (n = 2),
      IIdA21G1a (n = 1), and IIaA16G1R1 (n = 1). Subtype IIdA26G1 was found in a pig.
      These results were significantly different from previous Romanian reports, as the
      five subtypes of family IId identified in this study were never identified
      previously in this country. Thus, cattle may be a source of Cryptosporidium
      infections for humans and the transmission dynamics of C. parvum in Romania is
      more complex than previously believed. 

PMID- 25960547
TI  - The taxonomic identity and phylogenetic relationships of Cercaria pugnax and C.
      helvetica XII (Digenea: Lecitho-dendriidae) based on morphological and molecular
      data.
AB  - The present study analysed the taxonomic status and phylogenetic relationships of
      two species of xiphidiocercariae of the 'microcotylae' group, Cercaria pugnax La
      Valette St. George, 1855, from Viviparus viviparus (Linnaeus) in the Ukraine and
      Cercaria helvetica XII Dubois, 1928 from Bithynia tentaculata (Linnaeus) in
      Lithuania. Molecular phylogenetic analyses based on sequences of the ITS2 region
      and partial 28S gene of the nuclear rDNA revealed that both these
      xiphidiocercariae belong to the Lecithodendriidae Luhe, 1901 and represent larval
      stages of lecithodendriids parasitic in bats. Cercaria helvetica XII clustered
      with the typical representatives of the genus Lecithodendrium Looss, 1896, being
      very close, but not identical, to Lecithodendrium linstowi Dollfus, 1931.
      Sequences of C. pugnax matched exactly the sequences of adult Paralecithodendrium
      chilostomum (Mehlis, 1831). Morphological descriptions of the cercariae are
      included; these represent the first report of non-virgulate xiphidiocercariae
      belonging to the family Lecithodendriidae. Until now, the presence of glandular
      virgula organ in the region of the oral sucker was considered a robust
      synapomorphy for the Lecithodendriidae and several closely related families. Our
      results have shown that the relative importance of this character is in need of a
      re-assessment. 

PMID- 25960548
TI  - Developmental stages and fecundity of Lepeophtheirus simplex (Copepoda:
      Caligidae) parasitic on bullseye puffer fish (Sphoeroides annulatus).
AB  - Lepeophtheirus simplex Ho, Gomez et Fajer-Avila, 2001 is a parasite of
      Sphoeroides annulatus (Jenyns), an economically important fish species, with
      potential for aquaculture, in northwestern Mexico. The goal of this study was to
      describe the developmental stages under experimental conditions and seasonal
      fecundity of this parasite on wild fish. There are two naupliar, one copepodid,
      two chalimus and two pre-adult stages preceding the adult of L. simplex. The
      results support previous findings, which point out that the life cycle of the
      caligid copepods includes only six post-naupliar stages. The generation time from
      egg extrusion to adult for L. simplex was approximately 10 days at 22  degrees C.
      The body length of the ovigerous females ranged between 2.2 and 4.1 mm, and its
      fecundity between 12 and 36 eggs per string. Fecundity was negatively correlated
      with the egg size and positively correlated with the egg string length. Our data
      did not reveal significant differences in fecundity among sampling months, but
      ovigerous females were significantly larger in March (when water temperature was
      22  degrees C) than in June and July (when water temperature was 30  degrees C).
      To some extent, our fecundity results contrast with those found in species of sea
      lice from higher latitudes. Undoubtedly, biological information on different
      species of sea lice from different environmental conditions will enhance our
      understanding of their infection strategies and will be valuable, given the
      increasing interest in marine fish farming in Mexico. 

PMID- 25960549
TI  - How females of Achtheinus spp. (Pandaridae: Siphonostomatoida) attach to their
      elasmobranch hosts with notes on their effects on the hosts' fins.
AB  - Copepods of the genus Achtheinus Wilson, 1908 (Pandaridae) are parasites of
      elasmobranchs that attach to their fins, gill slits and around the nostrils.
      Specimens of Achtheinus pinguis Wilson, 1912 were collected and examined using
      histology and scanning electron microscopy to determine their way of attachment
      to the host and the possible effect on the host. They insert their antennae deep
      into the dermis of the shark's skin, which causes the most damage due to possible
      tissue compression and/or fibrosis as well as rupture of the connective tissue.
      Additionally, the presence of the copepod on the skin causes cell erosion of the
      epidermal cells and thus reduces the number of epidermal layers. The maxillipeds
      are used to attach to the placoid scales that cover the shark's skin and probably
      serve to keep the copepod and inserted antennae in position. This is accomplished
      by the insertion of the placoid scales into the flaccid corpus of the
      maxillipeds. Observed damage seems to be negligible to the shark apart from the
      possibility of secondary infection. 

PMID- 25960550
TI  - A new genus and species of proteocephalidean tapeworm (Cestoda), first parasite
      found in the driftwood catfish Tocantinsia piresi (Siluriformes: Auchenipteridae)
      from Brazil.
AB  - Frezella gen. n. is proposed to accommodate Frezella vaucheri sp. n. from poorly
      known auchenipterid fish, Tocantinsia piresi (Miranda Ribeiro), from the Xingu
      River, one of the principal tributaries of the lower Amazon River in Brazil. The
      new genus belongs to the Proteocephalinae because of the medullary position of
      the testes, ovary (yet some follicles penetrate to the cortex on the dorsal
      side), vitelline follicles and uterus. It differs from other proteocephaline
      genera in the morphology of the scolex, which includes a metascolex composed of
      two distinct zones: anterior, strongly wrinkled part posterior to the suckers,
      and posterior, sparsely folded zone. Frezella can also be differentiated by
      having the internal longitudinal musculature hypertrophied laterally on both
      sides, the presence of some ovarian follicles in the cortex on the dorsal side
      and the presence of additional pair of tiny, thin-walled osmoregulatory canals
      situated slightly dorsomedian to ventral canals. Frezella vaucheri is the first
      helminth parasite reported from T. piresi, which occurs in the lower reaches of
      the Amazon and Tocantins River basins in Brazil. 

PMID- 25960551
TI  - Ultrastructure and phylogeny of Glugea nagelia sp. n. (Microsporidia: Glugeidae),
      infecting the intestinal wall of the yellowfin hind, Cephalopholis hemistiktos
      (Actinopterygii: Serranidae), from the Red Sea.
AB  - A new microsporidian species of the genus Glugea Thelohan, 1891 parasitising the
      marine teleost fish Cephalopholis hemistiktos Ruppell, collected from the Red Sea
      in Saudi Arabia, is described on the basis of microscopic and molecular
      procedures. Spherical and whitish xenoma were observed adhering to the intestinal
      wall. The numerous spores contained within these xenoma, were ovoid to pyriform
      and measured 4.3-6.0 um (5.1 um) in length and 1.8-2.9 um (2.2 um) in width. The
      spore's wall was composed of two thick layers, which were thinner in the area
      contacting the anchoring disk. The latter appeared at the spore's anterior pole,
      in an eccentric position to the longitudinal axis. A lamellar polaroplast
      surrounded the uncoiled portion of the polar filament projected to the basal
      region of the spore, giving rise to 26-29 turns with winding from the base to the
      anterior zone of the spore. The posterior vacuole, located at the spore's
      posterior pole, and surrounded by the polar filament coils, was irregular and
      composed of light material. Molecular analysis of the rRNA genes, including the
      ITS region, was performed using maximum parsimony, neighbour-joining and maximum
      likelihood methods. The ultrastructural features observed, combined with the
      phylogenetic data analysed, suggest this parasite to be a new species of the
      genus Glugea. This is the first species of this genus to be reported from Saudi
      Arabia and is herein named Glugea nagelia sp. n. 

PMID- 25960552
TI  - Life cycle of Hepatozoon affluomaloti sp. n. (Apicomplexa: Haemogregarinidae) in
      crag lizards (Sauria: Cordylidae) and in culicine mosquitoes from South Africa.
AB  - A new haemogregarine species Hepatozoon affluomaloti sp. n. is described from
      erythrocytes in the peripheral blood of crag lizards Pseudocordylus melanotus
      (Smith) and Pseudocordylus subviridis (Smith) (Sauria: Cordylidae) from
      mountainous regions in the Eastern Free State, South Africa. This species can be
      distinguished from all other congeners based on its large size, staining
      properties and life cycle development in its vector, Culex (Afroculex) lineata
      (Theobald) (Diptera: Culicidae). Mature gamonts stain mostly uniformly pinkish
      purple with Giemsa, sometimes containing darker azurophilic granules anterior and
      posterior to the nucleus. The reflexed posterior extremity of the gamont stage
      sometimes stains slightly deeper purple and the nucleus is dense and placed in
      the posterior third of the parasite body. Merogonic stages of this haemogregarine
      occur in the liver tissues of P. melanotus with dizoic meronts. Macromeronts
      contains 2-7 macromerozoites and micromeronts contains 9-24 micromerozoites.
      Sporogonic developmental stages found in the proposed final host and vector, C.
      lineata, include large oocysts, measuring 54 * 48 um on average. Sporulating
      oocysts with 8 nuclei are present in mosquitoes 6-7 days post-feeding on infected
      lizards. Sporocysts with mature sporozoites measure 31.0 * 21.8 um on average and
      each contains 2-8 large sporozoites. It is suggested that transmission of
      infective sporozoites is achieved through predation of lizards on mosquitoes. 

PMID- 25960553
TI  - Carcinopodacarus polymorphus gen. n. et sp. n. from Guira guira (Cuculiformes:
      Cuculidae) in Brazil: a first example of male polymorphism in the family
      Dermationidae (Acariformes: Analgoidea).
AB  - Carcinopodacarus polymorphus gen. n. et sp. n. (Acariformes: Dermationidae:
      Dermationinae) is described from the guira cuckoo Guira guira (Gmelin)
      (Cuculiformes: Cuculidae) in Brazil. The new genus differs from the closest
      genus, Psittophagoides Fain, 1964, by the following features: in both sexes, the
      anterior spines of trochanters I and II are absent (vs present in
      Psittophagoides), setae d2 are distinctly developed (vs only alveoli), and genual
      setae mGI are absent (vs present); in males, the hysteronotal shield is split
      transversally at the level of trochanters III (vs hysteronotal shield entire); in
      females, the platelets situated posterior to the propodonotal shield are absent
      (vs present), the metapodosomal sclerites are present (vs absent), and the adanal
      shields are fused anteriorly to each other (vs separated from each other). In
      this species, andropolymorphism is detected for the first time for the family. It
      involves various characters but the most impressive feature is the structure of
      legs III. In hetero- and mesomorphic males, these legs are strongly hypertrophied
      and have a distinct ventral spur on femora III; in homeomorphic males, legs III
      are not modified and subequal to legs IV. 

PMID- 25960554
TI  - Kudoa saudiensis sp. n. (Myxosporea: Multivalvulida) infecting oocytes of the
      Indian mackerel Rastrelliger kanagurta (Perciformes: Scombridae).
AB  - During a survey the occurrence of Kudoa quraishii Mansour, Harrath, Abd-Elkader,
      Alwasel, Abdel-Baki et Al Omar, 2014, recently identified in the muscles of the
      Indian mackerel, Rastrelliger kanagurta (Cuvier), a species of Kudoa Meglitsch,
      1947 infecting oocytes of mature females of the same host fish was found. The new
      species, for which the name Kudoa saudiensis sp. n. is proposed, infects oocytes
      that are enlarged with a whitish colour. The parasite develops in vesicular
      polysporous plasmodia within the oocyte. Infection occurs with a mean prevalence
      of 20% (7/35) of examined females. Mature spores are quadratic in shape in apical
      view, having four equal valves and four symmetrical polar capsules. Fresh spores
      are 2.4-3.6 um long (mean +/- SD 3.1 +/- 0.3 um), 4.3-5.4 um (4.7 +/- 0.3 um)
      wide and 3.4-4.3 um (3.8 +/- 0.3 um) in thickness and long. The smaller size of
      the new Kudoa species was the distinctive feature that separates it from all
      previously described species. Molecular analysis based on the SSU rDNA sequences
      shows that the highest percentage of similarity of 98.5% was observed with K.
      ovivora Swearer et Robertson, 1999, reported from oocytes of labroid fish from
      the Caribbean coasts of Panama. The percentage of similarity was 98% with K.
      azevedoi Mansour, Thabet, Chourabi, Harrath, Gtari, Al Omar et Ben Hassine, 2013
      and 89% with K. quraishii. Phylogenetic analysis of the SSU and LSU rDNA data
      revealed a consistent of the new species with K. azevedoi and K. ovivora. Our
      findings support the creation of Kudoa saudiensis sp. n. that infects oocytes of
      the Indian mackerel Rastrelliger kanagurta. 

PMID- 25960555
TI  - Lemuralges propithecus sp. n. (Acariformes: Psoroptidae), an ectoparasite of the
      diademed sifaka Propithecus diadema (Primates: Indriidae).
AB  - A new species of the genus Lemuralges Fain, 1963 (Acariformes: Psoroptidae:
      Makialginae) is described from the Malagasy lemur Propithecus diadema (Bennett)
      (Primates: Indriidae) based on all postembryonic instars. This new species
      differs from the only known species in this genus, Lemuralges intermedius Fain,
      1963, by the following features: both sexes of L. propithecus sp. n. show a pair
      of medioventral projections of the subcapitulum (vs without projections in L.
      intermedius) and the propodonotal shield is slightly ornamented (vs
      unornamented); in males the hysteronotal shield is completely covered by
      longitudinal striae (vs median part without striae), setae c2 are 120-140 um long
      (vs 200-210 um long), and femur III has a short transverse furrow dorsally (vs a
      longitudinal furrow); in females, setae h2 are, at least, 2 times shorter than h3
      (vs slightly longer, or subequal to, h3), tibia IV has a ventro-apical projection
      (vs without projection). Larvae and protonymphs of the new species show some
      unique developmental delays. Female and male tritonymphs differ by their external
      morphology. 

PMID- 25960556
TI  - Four new species of Acanthobothrium van Benden, 1850(Cestoda:
      Onchoproteocephalidea) from the guitarfish, Rhynchobatus cf. djiddensis
      (Elasmobranchii: Rhynchobatidae), from the Persian Gulf and Gulf of Oman.
AB  - Four new species of Acanthobothrium van Beneden, 1850 are described from
      guitarfish, Rhynchobatus cf. djiddensis (Forsskal), collected from the Gulf of
      Oman and Persian Gulf. Acanthobothrium janineae sp. n., a category 1 species,
      differs from all congeners in category 1 by having a long vagina extending into
      the vas deferens and different, proglottid and testis number except
      Acanthobothrium hypermekkolpos Fyler et Caira, 2010. Acanthobothrium fylerae sp.
      n., a category 1 species, can be differentiated by a combination of characters
      including the total length, proglottid and testis number, cirrus sac shape, and
      the length of the vagina and ovarian lobes. Both new species are similar to A.
      hypermekkolpos reported from Rhynchobatus laevis (Bloch et Schneider) from
      Australia in their scolex proper length, hook size and muscular pad,
      respectively. Acanthobothrium asrinae sp. n., a category 1 species, differs from
      other category 1 species by the shape of its hooks and the position of the
      tubercle at the mid-length of the axial prongs; in this respect it resembles A.
      bartonae Campbell et Beveridge, 2002 reported from Australia. Acanthobothrium
      jamesi sp. n. is among six category 1 species with post-ovarian testes. It
      differs from these species by total length, proglottid and testis number and the
      extension of the ovarian lobes. Although it is thought that R. djiddensis occurs
      in the region, the identities of the hosts of the newly described Acanthobothrium
      species await verification. There are two forms of host in the region and were
      designated as R. cf. djiddensis 1 and R. cf. djiddensis 2. More taxonomic work
      and the use of molecular techniques are needed to resolve the true identity of
      the host species. 

PMID- 25960557
TI  - Life cycle and settlement of an Australian isolate of Ichthyophthirius
      multifiliis Fouquet, 1876 from rainbow trout.
AB  - Ichthyophthirius multifiliis Fouquet, 1876, a ciliate parasite, is a cosmopolitan
      and problematic parasite of cultured freshwater fish. Each geographical isolate
      of I. multifiliis has variations in life cycle timing under different abiotic
      water conditions, such as temperature and salinity. We assessed the effects of
      salinity and temperature on the development and the preferred settlement site of
      a temperate Australian isolate of I. multifiliis. The time until theront release
      was significantly different between each temperature; development time was
      longest at 5  degrees C with a mean time of 189 h and decreased to a mean time of
      11.7 h at 30  degrees C. At 5  degrees C our isolate produced a mean of 267
      theronts per tomont, which increased to a mean of 493 theronts at 25  degrees C
      and reduced to a mean of 288 theronts at 30  degrees C. Theront length showed an
      inverse relationship to temperature; mean length was 62 MUm at 5  degrees C and
      41 MUm at 30  degrees C. Our isolate reproduced faster at all temperatures and a
      greater sensitivity to salinity than all reported profiles for temperate
      isolates. Parasite abundance was highest on the dorsal region of the fish. An
      accurate understanding of temperature-life cycle information and optimal region
      to sample for surveillance will aid in the development of specific management
      plans for the Australian isolate of I. multifiliis, facilitating the strategic
      timing of treatments. 

PMID- 25960558
TI  - Host-parasite and phylogenetic relationships of Myxobolus filamentum sp. n.
      (Myxozoa: Myxosporea), a parasite of Brycon orthotaenia (Characiformes:
      Bryconidae) in Brazil.
AB  - Myxobolus filamentum sp. n. was found infecting gill filaments of three of 39
      Brycon orthotaenia Gunther specimens examined (8%), which were taken from the
      river Sao Francisco in Minas Gerais state, Brazil. Plasmodia of the parasite were
      white and long, measuring 5 mm in lenght. Mature spores of M. filamentum sp. n.
      were oval from the frontal view and biconvex from the lateral view, measuring 7.5
      9.7 um (9.0 +/- 0.3 um) in length and 5.2-7.3 um (6.2 +/- 0.4 um) in width. The
      polar capsules were elongated and equal in size, measuring 3.8-5.5 um (4.7 +/-
      0.3 um) in length and 1.3-2.2 um (1.7 +/- 0.1 um) in width. The development of
      the parasite led to compression of the adjacent tissues and inflammatory
      infiltrate with granulocytic cells. Ultrastructural observation revealed that the
      plasmodia were delimited by two membranes, which had numerous and extensive
      pinocytotic channels extending into the wide ectoplasm zone. The plasmodial wall
      exhibited abundant villi-like projections and a thin layer of granular material
      prevented direct contact between the plasmodial wall and the host tissue.
      Phylogenetic analysis, based on 18S rDNA, showed M. filamentum sp. n. as a sister
      species of Myxobolus oliveirai Milanin, Eiras, Arana, Maia, Alves, Silva,
      Carriero, Ceccarelli et Adriano, 2010, a parasite of other fish species of the
      genus Brycon Muller et Troschel from South America. 

PMID- 25960559
TI  - Association between latent toxoplasmosis and clinical course of schizophrenia -
      continuous course of the disease is characteristic for Toxoplasma gondii-infected
      patients.
AB  - The aim of the present study was to investigate the association between various
      clinical aspects of schizophrenia and seropositivity against Toxoplasma gondii
      (Nicolle et Manceaux, 1908). We selected 94 patients with schizophrenia and
      investigated the seropositivity rate for anti-T. gondii IgG antibodies by ELISA.
      Clinical parameters of schizophrenic patients such as illness type and status,
      clinical course, awareness of the illness and need for electroconvulsive therapy
      (ECT) were compared with their serological status. Anti-T. gondii IgG antibodies
      were detected in 43 (46%) of schizophrenic patients. Chronic patients had a rate
      of 34 (72%) seropositivity, whereas 9 (22%) of the patients with partial
      remission showed evidence of latent toxoplasmosis. Of continuous patients, 35
      (81%) were found to be seropositive and this rate was significantly more than in
      the other groups. The rate of latent toxoplasmosis was detected significantly
      higher in patients who lack awareness of schizophrenia (36, i.e. 72%) than the
      patients who were aware of their illnesses (7, i.e. 16%). Anti-T. gondii IgG
      antibodies were detected in 38 (70%) of ECT performed patients while this
      percentage was 13% in the ones who had never been treated with ECT. This
      difference was also statistically significant. We showed that Toxoplasma-infected
      subjects had 15* higher probability of having continuous course of disease than
      Toxoplasma-free subjects. Our results put forth the possibility of latent
      toxoplasmosis to have a negative impact on the course of schizophrenia and
      treatment response of schizophrenic patients. 

PMID- 25960560
TI  - Characterisation of microsatellite loci in two species of lice, Polyplax serrata
      (Phthiraptera: Anoplura: Polyplacidae) and Myrsidea nesomimi (Phthiraptera:
      Amblycera: Menoponidae).
AB  - Polymorphic microsatellite loci were characterised for two louse species, the
      anopluran Polyplax serrata Burmeister, 1839, parasitising Eurasian field mice of
      the genus Apodemus Kaup, and the amblyceran Myrsidea nesomimi Palma et Price,
      2010, found on mocking birds endemic to the Galapagos Islands. Evolutionary
      histories of the two parasites show complex patterns influenced both by their
      geographic distribution and through coevolution with their respective hosts,
      which renders them prospective evolutionary models. In P. serrata, 16 polymorphic
      loci were characterised and screened across 72 individuals from four European
      populations that belong to two sympatric mitochondrial lineages differing in
      their breadth of host-specificity. In M. nesomimi, 66 individuals from three
      island populations and two host species were genotyped for 15 polymorphic loci.
      The observed heterozygosity varied from 0.05 to 0.9 in P. serrata and from 0.0 to
      0.96 in M. nesomimi. Deviations from the Hardy-Weinberg equilibrium were
      frequently observed in the populations of both parasites. Fst distances between
      tested populations correspond with previous phylogenetic data, suggesting the
      microsatellite loci are an informative resource for ecological and evolutionary
      studies of the two parasites. 

PMID- 25960561
TI  - The occurrence of metacercariae of Petasiger (Digenea: Echinostomatidae) in an
      unusual site, within the lateral line scales of cyprinid fishes.
AB  - During a regular veterinary inspection of fishes from Lake Balaton, Hungary,
      echinostomatid metacercariae (Digenea), with collar spines characteristic of
      species of the genera Petasiger Dietz, 1909 and Paryphostomum Dietz, 1909, were
      found in the lateral line scales of a roach Rutilus rutilus (Linnaeus), an
      apparently unique site. In a subsequent examination of 586 fishes from 20
      different species, similar infections were found in 11 species. The infection was
      virtually restricted to the lateral line scales, other scales being infected only
      incidentally. These encysted metacercariae had 27 collar spines, including eight
      larger angle spines and 19 smaller dorsal spines arranged in two rows. Two types
      of metacercarial cyst were found. One type had a cyst diameter of 138-171 um *
      105-120 um and three central dorsal spines that were larger than the remainder
      and tended to resemble the angle spines. The second type of metacercarial cyst
      had a diameter of 128-157 um * 105-115 um and all 19 dorsal spines of the
      metacercaria were of a similar size. ITS sequences of the second type of
      metacercaria exhibited a 100% similarity to sequences of two adult Petasiger
      phalacrocoracis (Yamaguti, 1939) specimens collected from the gut of
      Phalacrocorax carbo (Linnaeus) in Hungary and to P. phalacrocoracis deposited in
      the GenBank database. Sequences obtained from two metacercariae of the first type
      showed a 2.8-2.9 % difference from sequences of the second type of metacercaria
      and from those of adult specimens of P. phalacrocoracis from cormorants. Based on
      these results, the second type metacercaria is considered to be a larval stage of
      P. phalacrocoracis, but the identity of the first type is uncertain. The unusual
      location of these metacercariae in the lateral line scales is discussed in
      relation to their transmission. 

PMID- 25960563
TI  - Damselflies (Zygoptera) as paratenic hosts for Serpinema trispinosum and its
      report from turtle hosts from Oklahoma, USA.
AB  - Third-stage larvae of the nematode Serpinema trispinosum (Leidy, 1852) were
      collected from the midgut of four of five species of adult damselflies
      (Zygoptera) from a non-irrigated restored semipermanent wetland located in
      Stillwater, Oklahoma, USA. Of the four infected damselfly species, prevalence and
      mean abundance was highest for the southern spreadwing, Lestes disjunctus
      australis Walker (10%, 0.2 +/- 0.8) and lowest for the familiar bluet, Enallagma
      civile (Hagen) (2.5%, 0.04 +/- 0.3); whereas mean intensities were lowest for the
      citrine forktail, Ischnura hastata (Say) (1.5 +/- 0.5) and the eastern forktail,
      Ischnura verticalis (Say) (1.0 +/- 0). This is the first record of larvae of S.
      trispinosum from damselflies. Serpinema trispinosum adults have been reported
      from 18 species of North and Central American freshwater turtles, whereas
      microcrustaceans such as copepods serve as intermediate hosts and snails, fish
      and amphibians serve as paratenic hosts in this nematode's life cycle. However,
      dietary studies of the 18 species of freshwater turtles reported as definitive
      hosts for S. trispinosum indicate that aquatic insects including damselflies are
      more commonly reported in turtle diets than are fish or amphibians. Additionally,
      unlike snails and amphibians, larval damselflies predominantly feed on
      microcrustaceans, and our observation of S. trispinosum infecting damselflies may
      reflect the importance of these insects as paratenic hosts. In the present study,
      we provide new host information and measurements for third-stage larvae of S.
      trispinosum from damselfly hosts along with measurements for adult male and
      female S. trispinosum from turtle hosts from Oklahoma, USA. 

PMID- 25960562
TI  - A new species of Wallinia Pearse, 1920 (Digenea: Allocreadiidae) in Astyanax
      mexicanus (Characidae) from Mexico revealed by morphology and sequences of the
      28S ribosomal RNA gene.
AB  - Wallinia mexicana sp. n. is described from the Mexican tetra, Astyanax mexicanus
      (De Filippi) (Characidae Weitzman), from two localities in northern Mexico. The
      new species can be distinguished from the two congeneric species, described from
      small-bodied characids in South and Central America, mainly by the posterior
      extent of the vitelline follicles (halfway between the posterior testis and the
      end of the caeca), by having a larger oesophagus, testes that are always oblique,
      and eye-spot remnants. The distinct status of the new species was confirmed by
      molecular data (28S rRNA gene sequences). Phylogenetic analysis suggests the new
      species is the sister species of W. chavarriae Choudhury, Hartvigsen et Brooks,
      2002 described from characids in northwestern Costa Rica. Additionally, genetic
      divergence between these congeners reached 3.3%, a value higher than that
      observed for closely related species pairs of allocreadiids for that molecular
      marker. Based on these new findings, recently published records of this new
      species as Magnivitellinum simplex Kloss, 1966 and Creptotrematina
      aguirrepequenoi Jimenez-Guzman, 1973 in Astyanax mexicanus from Durango and San
      Luis Potosi states, respectively, are corrected. 

PMID- 25960564
TI  - Observations on sporulation of Eimeria bovis (Apicomplexa: Eimeriidae) from the
      European bison Bison bonasus: effect of temperature and potassium dichromate
      solution.
AB  - The present study was designed to determine the influence of temperature and the
      addition of potassium dichromate solution (K2Cr2O7) on the efficiency of
      sporulation of Eimeria bovis (Zublin, 1908), a coccidian species most commonly
      diagnosed in European bison Bison bonasus (Linnaeus). Sporulation under
      conventional conditions (2.5% dichromate solution, 23  degrees C) was completed
      on the fourth day of incubation (control), whereas the oocyst development took
      two days more at the temperature of 18  degrees C, and two days less at 28 
      degrees C. Additionally, experimental sporulation of E. bovis at the temperature
      of 23  degrees C in the environment of sterilised tap water (without any
      preservation) took 9 days more compared to control. Finally, oocyst development
      took 16 weeks when the faces were stored in the refrigerator (3-5  degrees C)
      without any special additives. Overall, our results indicate that K2Cr2O7,
      besides the temperature, plays a crucial role in the process of sporulation of
      oocysts under laboratory conditions, as the longest delay in sporogony was
      observed when the faeces were stored without any other additives in the
      temperature of the refrigerator. 

PMID- 25960565
TI  - Effect of dietary guild (frugivory and insectivory) and other host
      characteristics on ectoparasite abundance (mite and nycteribiid) of chiropterans.
AB  - Ectoparasites are an important factor in bat health due to emergent diseases and
      their associated threats to global public health. The diverse foraging habits of
      bats expose them to different surfaces which may influence ectoparasite
      infestations. In spite of these, most studies often overlook dietary
      specialisations when observing ectoparasite loads. The present paper
      quantitatively investigates whether foraging strategies as well as other host
      characteristics (sex, age, trunk and patagial area) influence ectoparasite
      (nycteribiids and mites) loads of bats. Ectoparasite counts and morphometric data
      were taken from mist net captures of bats. We then developed and compared models
      for modeling bat ectoparasite abundance under various distributions using
      generalised linear models. The negative binomial distribution consistently proved
      to be adequate for modeling mite, nycteribiid and total ectoparasite abundance
      based on information-theoretic approaches. Generally, females and frugivores had
      higher ectoparasite loads conditional on bat sex and diet, respectively. Contrary
      to nycteribiid abundance, mite abundance was positively related to patagial area.
      Thus, our findings suggest that dietary guild, sex and patagia of hosts (as well
      as age-nycteribiid abundance) are significant determinants of ectoparasite
      abundance. 

PMID- 25960566
TI  - Proteomic analysis of potential immunoreactive proteins from muscle larvae and
      adult worms of Trichinella spiralis in experimentally infected pigs.
AB  - The present study was undertaken to identify potentially immunoreactive proteins
      of the muscle larvae (ML) and adult stage (Ad) of the nematode Trichinella
      spiralis Owen, 1835. To identify immunoreactive proteins that are specifically
      recognised by anti-Trichinella antibodies, ML and Ad crude extracts and their
      excretory-secretory (E-S) products were subjected to sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblot with serum samples
      from pigs experimentally infected with T. spiralis. A total of 18 bands were
      selected for final identification by liquid chromatography-tandem mass
      spectrometry. To further understand the functions of the proteins identified in
      this study, gene ontology terms were applied. Results showed that the specific
      antibodies against T. spiralis reacted with protein bands matching heat shock
      proteins, aminopeptidase, enolase, isocitrate dehydrogenase NADP-dependent,
      tropomyosin, P49 antigen, serine proteinase, secreted 5'-nucleotidase, antigen
      targeted by protective antibodies, 53 kDa E-S antigen, putative trypsin and
      paramyosin. Three proteins common for both adult stage and muscle larvae,
      including heat shock proteins, enolase and 5'-nucleotidase, might play important
      role during T. spiralis infection. These proteins are presumably presented to the
      host immune system and may induce humoral immune response. Thus, these proteins
      may be potential antigens for early diagnosis and the development of a vaccine
      against the parasite. 

PMID- 25960567
TI  - Screening for anthelmintic resistance in equid strongyles (Nematoda) in Romania.
AB  - Resistance to anthelmintic medication of equid strongyles is a worldwide
      phenomenon and for this reason systematic investigations of resistant parasite
      populations are necessary. The purpose of the present study was to investigate
      the presence and distribution of equid strongyles resistant to the anthelmintics
      used in Romania, as well as the pre-treatment and post-treatment prevalence of
      species of strongylid nematodes. The Faecal Egg Count Reduction Test was
      performed between 2010 and 2013 on a total number of 588 horses and 23 donkeys
      from 26 locations (subgroups). Animals of the first group (I) consisting of
      subgroups no. 1-11 were treated with Albendazole (ABZ), those of the second group
      (II) consisting of subgroups no. 12-23 with Fenbendazole (FBZ), while Ivermectin
      (IVM) was used on animals of the third group (III) consisting of subgroups no. 24
      26. Resistant strongyles have been found in 82% (average lower limit of the 95%
      confidence interval, LCL95%, was 65) of the total equids from the group treated
      with ABZ. In the group of horses treated with FBZ, resistant strongyles were
      identified in 75% of the subgroups (LCL95% = 44). No resistant strongyles have
      been identified in IVM-treated horse groups (LCL95% = 98). The pre-treatment
      prevalence of the species of the Strongylinae Muller, 1780 was 22%, whereas that
      with nematodes of the subfamily Cyathostominae Molin, 1861 78%. Post-treatment
      reduction of strongyline nematodes was observed (5%), which demonstrates the
      sensitivity of large strongyles to common anthelmintics. The post-treatment
      prevalence of cyathostomes was of 95%, which proves their resistance, especially
      to ABZ- and FBZ-based anthelmintics. 

PMID- 25960568
TI  - A comparative study of Ligophorus uruguayense and L. saladensis (Monogenea:
      Ancyrocephalidae) from Mugil liza (Teleostei: Mugilidae) in southern Brazil.
AB  - Representatives of Ligophorus Euzet et Suriano, 1977 were found on the gills of
      Mugil liza Valenciennes caught in southern Brazil. They were identified as
      Ligophorus uruguayense Failla Siquier et Ostrowski de Nunez, 2009 and Ligophorus
      saladensis Marcotegui et Martorelli, 2009, even though specific identification
      proved to be difficult due to inconsistencies in some diagnostic features
      reported for these two species. Therefore, a combined morphological and molecular
      approach was used to critically review the validity of these species, by means of
      phase contrast and confocal fluorescence microscopical examination of sclerotised
      hard parts, and assessing the genetic divergence between L. saladensis, L.
      uruguayense and their congeners using rDNA sequences. The main morphological
      differences between the two species relate to the shape of the accessory piece of
      the penis and the median process of the ventral bar. The accessory piece in L.
      uruguayense is shorter than in L. saladensis, has a cylindrical, convex upper
      lobe and straight lower lobe (vs with the distal tip of the lower lobe turning
      away from the upper lobe in the latter species). The ventral bar has a V-shaped
      anterior median part in L. uruguayense (vs U-shaped in L. saladensis). The two
      species are suggested to be part of a species complex together with L.
      mediterraneus Sarabeev, Balbuena et Euzet, 2005. We recommend to generalise such
      comparative assessment of species of Ligophorus for a reliable picture of the
      diversity and diversification mechanisms within the genus, and to make full use
      of its potential as an additional marker for mullet taxonomy and systematics. 

PMID- 25960569
TI  - Post-marketing experience with nevirapine extended release (XR) tablets:
      effectiveness and tolerability in a population-based cohort in British Columbia,
      Canada.
AB  - BACKGROUND: Nevirapine 400 mg extended release tablets (nevirapine-XR) are a once
      daily alternative to nevirapine 200 mg immediate release tablets (nevirapine-IR).
      Study objectives were to describe the effectiveness and tolerability of
      nevirapine-XR in clinical practice and, for patients who switched from once daily
      2*200 mg nevirapine-IR to nevirapine-XR, compare virological suppression and
      plasma nevirapine concentrations during each treatment period. METHODS: HIV-1
      infected adults entered the study cohort if they initiated nevirapine-XR in
      British Columbia (BC) Canada between 1 April 2012 and 30 September 2012 and were
      followed until 30 September 2013. Demographic and clinical variables were
      abstracted from the BC Centre for Excellence in HIV/AIDS databases. Patients who
      switched from once daily nevirapine-IR to nevirapine-XR were monitored for 6
      months pre- and post-switch with comparison of virological suppression
      (McNeamer's test) and median random plasma nevirapine concentrations (Wilcoxon
      Mann-Whitney test) in each period. RESULTS: The 536 nevirapine-XR-treated
      patients were 96% male, median (IQR) age 49.9 (44.0-56.9) years. Median follow-up
      was 15.6 (14.7-16.5) months, with 474/536 (88%) maintaining virological
      suppression. Emergent drug resistance developed in 5/536 (1%), adverse drug
      reactions in 17/536 (3%) and, although 31/536 (6%) reported 'whole' tablets in
      their stools, this was not associated with adverse outcomes. Among the 305
      patients who switched from nevirapine-IR to nevirapine-XR, median (IQR) random
      plasma nevirapine concentration was higher during nevirapine-IR 5,000 (3,690
      6,090) ng/ml than nevirapine-XR 3,930 (3,050-5,150) ng/ml (P<0.001), but there
      was no difference in virological suppression, 89% and 87% respectively (P=0.414).
      CONCLUSIONS: This post-marketing study affirms the effectiveness and tolerability
      of nevirapine-XR as an alternative to nevirapine-IR in adults.

PMID- 25960570
TI  - Cilia and Diseases.
AB  - In recent decades, cilia have moved from relative obscurity to a position of
      importance for understanding multiple complex human diseases. Now termed the
      ciliopathies, these diseases inflict devastating effects on millions of people
      worldwide. In this review, written primarily for teachers and students who may
      not yet be aware of the recent exciting developments in this field, we provide a
      general overview of our current understanding of cilia and human disease. We
      start with an introduction to cilia structure and assembly and indicate where
      they are found in the human body. We then discuss the clinical features of
      selected ciliopathies, with an emphasis on primary ciliary dyskinesia, polycystic
      kidney disease, and retinal degeneration. The history of ciliopathy research
      involves a fascinating interplay between basic and clinical sciences, highlighted
      in a timeline. Finally, we summarize the relative strengths of individual model
      organisms for ciliopathy research; many of these are suitable for classroom use.

PMID- 25960571
TI  - Are Nectarines to Blame? A Case Report and Literature Review of Spontaneous
      Bacterial Peritonitis Due to Listeria monocytogenes.
AB  - Spontaneous bacterial peritonitis (SBP) is a frequent and potentially deadly
      complication of ascites in patients with end-stage liver disease. Unlike other
      pathogens more commonly implicated in SBP, Listeria monocytogenes is a nonenteric
      organism that maybe acquired either sporadically or in the setting of foodborne
      outbreaks. Listeria is an unusual cause of SBP that presents particular
      management challenges because of the organism's intrinsic resistance to first
      line and empiric SBP treatment that would otherwise include third-generation
      cephalosporins. We present here a case of Listeria SBP in a 68-year-old man with
      previously unidentified cirrhosis. His infection occurred in the context of a
      nationwide fruit recall for Listeria contamination, prompting an epidemiologic
      investigation. After describing the case, we then review the extant literature on
      Listeria peritonitis. To date, no case studies on Listeria SBP have
      systematically described risk factors for Listeria acquisition. As incidence of
      Listeria SBP is increasing, however, knowledge of patient risk factors,
      especially foodborne exposure risks, may be important in preventing future
      episodes of Listeria SBP, and in accurately monitoring foodborne outbreaks.

PMID- 25960572
TI  - Pandemics: waves of disease, waves of hate from the Plague of Athens to A.I.D.S.
AB  - This article briefly surveys the history of pandemics in the West, contesting
      long-held assumptions that epidemics sparked hatred and blame of the 'Other', and
      that it was worse when diseases were mysterious as to their causes and cures. The
      article finds that blame and hate were rarely connected with pandemics in
      history. In antiquity, epidemics more often brought societies together rather
      than dividing them as continued to happen with some diseases such as influenza in
      modernity. On the other hand, some diseases such as cholera were more regularly
      blamed than others and triggered violence even after their agents and mechanisms
      of transmission had become well known.

PMID- 25960573
TI  - Competition on the range: science vs. perception in a bison-cattle conflict in
      the western USA.
AB  - 1. Competition between livestock and wild ungulates is commonly perceived to
      occur on shared rangelands. In the Henry Mountains (HM) of Utah, a free-ranging
      population of bison Bison bison has raised concerns among ranchers holding
      grazing permits on these public lands. Bison are the most conspicuous potential
      competitors with cattle, but lagomorphs (mainly jackrabbits Lepus californicus)
      are also abundant in this area. The local ranching community is applying
      political pressure on state and federal agencies to resolve 'the bison problem',
      but the relative grazing impacts of bison, cattle and lagomorphs have not
      previously been quantified. 2. We constructed 40 grazing exclosures (each 5.95
      m2) in the conflict area: 20 excluded bison + cattle ('partial') and 20 excluded
      bison + cattle + lagomorphs ('full'). All exclosures, each with a paired open
      reference plot, were monitored for 1 year, and above-ground plant production was
      measured. GPS telemetry (bison) and scheduled grazing (cattle) allowed visitation
      to be quantified for each ungulate species based on the number of 'animal days'
      in the area. Rancher perceptions of wildlife-cattle interactions were recorded in
      a questionnaire survey. 3. Ranchers perceived bison as a high-level competitor
      with cattle, whereas lagomorphs were perceived as low-level competitors. 4.
      Grazed reference plots yielded an average (+/-SE) of 22.7 g m-2 (+/-5.16) of
      grass, compared to 36.5 g m-2 (+/-7.33) in the partial exclosures and 43.7 g m-2
      (+/-7.61) in the full exclosures. Exclusion of large herbivores thus resulted in
      a 13.8 g m-2 increase in grass biomass relative to the reference plots (P =
      0.005), with the additional exclusion of lagomorphs resulting in a further 7.18 g
      m-2 increase (P = 0.048). 5. Overall, lagomorphs accounted for 34.1%, bison 13.7%
      and cattle 52.3% of the total grass biomass removed by all herbivores on the
      shared range. 6.Synthesis and applications. Cattle face a greater competitive
      challenge from lagomorphs than from bison in the study area. This case study
      illustrates the need for science-based management of social-ecological systems in
      which even long-term resource users might underestimate the complexities of
      trophic interactions. Attention should be redirected at the lagomorphs and their
      main predators, coyotes Canis latrans, which are currently subject to population
      control. To reduce negative perceptions among local ranchers, options should be
      explored to incorporate benefit-sharing into the management of the bison
      population.

PMID- 25960574
TI  - Effects of reduced salinity on the photosynthetic characteristics and
      intracellular DMSP concentrations of the red coralline alga, Lithothamnion
      glaciale.
AB  - Mid- to high-latitude fjordic coastal environments experience naturally variable
      salinity regimes. Climate projections suggest that freshwater input into the
      coastal ocean will increase in the future, exposing coastal organisms to further
      periods of reduced salinity. This study investigated the effect of low salinity
      on Lithothamnion glaciale, a red coralline alga found in mid- to high-latitude
      fjordic regions, during a 21-day experiment. Specific measurements included: the
      intracellular concentration of dimethylsulphoniopropionate (DMSP, an algal
      secondary metabolite and major precursor to the climatically active gas
      dimethylsulphide), pigment composition and photosynthetic characteristics. No
      significant difference in intracellular DMSP concentrations was observed between
      treatments, suggesting that the primary function for DMSP in L. glaciale is not
      as a compatible solute, perhaps favouring an antioxidant role . Photosynthetic
      parameters (including pigment composition) exhibited a mixed response, suggesting
      some degree of photosynthetic resilience to reduced salinity. This study provides
      evidence of intracellular mechanisms adopted by L. glaciale in response to
      reduced salinity. This has significant implications for the survival of L.
      glaciale under a projected freshening scenario and provides organism-level detail
      to ecosystem-level projected changes should lower-salinity conditions become more
      frequent and more intense in the future.

PMID- 25960575
TI  - A Moderated Nonlinear Factor Model for the Development of Commensurate Measures
      in Integrative Data Analysis.
AB  - Integrative data analysis (IDA) is a methodological framework that allows for the
      fitting of models to data that have been pooled across two or more independent
      sources. IDA offers many potential advantages including increased statistical
      power, greater subject heterogeneity, higher observed frequencies of low base
      rate behaviors, and longer developmental periods of study. However, a core
      challenge is the estimation of valid and reliable psychometric scores that are
      based on potentially different items with different response options drawn from
      different studies. In Bauer and Hussong (2009) we proposed a method for obtaining
      scores within an IDA called moderated nonlinear factor analysis (MNLFA). Here we
      move significantly beyond this work in the development of a general framework for
      estimating MNLFA models and obtaining scale scores across a variety of settings.
      We propose a five step procedure and demonstrate this approach using data drawn
      from n=1972 individuals ranging in age from 11 to 34 years pooled across three
      independent studies to examine the factor structure of 17 binary items assessing
      depressive symptomatology. We offer substantive conclusions about the factor
      structure of depression, use this structure to compute individual-specific scale
      scores, and make recommendations for the use of these methods in practice.

PMID- 25960576
TI  - Preparation of azidoaryl- and azidoalkyloxazoles for click chemistry.
AB  - A series of azidoaryl- and azidoalkyl(diphenyl)oxazole scaffolds were warranted
      for biofilm inhibition studies. Cyclization of azidoaryl- or azidoalkyl esters of
      benzoin with ammonium acetate in acetic acid gives 2-azidoaryl- or 2-azidoalkyl
      4,5-diphenyloxazoles. The azidoaryl esters are prepared from the corresponding
      azidocarboxylic acids/acid chlorides while the azidoalkyl esters are prepared
      from the corresponding haloalkyl esters.

PMID- 25960578
TI  - Representing Micro-Macro Linkages by Actor-Based Dynamic Network Models.
AB  - Stochastic actor-based models for network dynamics have the primary aim of
      statistical inference about processes of network change, but may be regarded as a
      kind of agent-based models. Similar to many other agent-based models, they are
      based on local rules for actor behavior. Different from many other agent-based
      models, by including elements of generalized linear statistical models they aim
      to be realistic detailed representations of network dynamics in empirical data
      sets. Statistical parallels to micro-macro considerations can be found in the
      estimation of parameters determining local actor behavior from empirical data,
      and the assessment of goodness of fit from the correspondence with network-level
      descriptives. This article studies several network-level consequences of dynamic
      actor-based models applied to represent cross-sectional network data. Two
      examples illustrate how network-level characteristics can be obtained as emergent
      features implied by micro-specifications of actor-based models.

PMID- 25960577
TI  - Design and synthesis of novel prostaglandin E2 ethanolamide and glycerol ester
      probes for the putative prostamide receptor(s).
AB  - Novel prostaglandin-ethanolamide (PGE2-EA) and glycerol ester (2-PGE2-G) analogs
      were designed and synthesized to aid in the characterization of a putative
      prostamide receptor. Our design incorporates the electrophilic isothiocyanato and
      the photoactivatable azido groups at the terminal tail position of the prototype.
      Stereoselective Wittig and Horner-Wadsworth-Emmons reactions install the head and
      the tail moieties of the PGE2 skeleton. The synthesis is completed using
      Mitsunobu azidation and peptide coupling as the key steps. A chemoenzymatic
      synthesis for the 2-PGE2-G is described for first time.

PMID- 25960579
TI  - Geostatistical Microscale Study of Magnetic Susceptibility in Soil Profile and
      Magnetic Indicators of Potential Soil Pollution.
AB  - Directional variograms, along the soil profile, can be useful and precise tool
      that can be used to increase the precision of the assessment of soil pollution.
      The detail analysis of spatial variability in the soil profile can be also an
      important part of the standardization of soil magnetometry as a screening method
      for an assessment of soil pollution related to the dust deposition. The goal of
      this study was to investigate the correlation between basic parameters of spatial
      correlations of magnetic susceptibility in the soil profile, such as a range of
      correlation and a sill, and selected magnetometric indicators of soil pollution.
      Magnetic indicators were an area under the curve of magnetic susceptibility
      versus a depth in the soil profile, values of magnetic susceptibility at depths
      ranging from 1 to 10 cm, and maximum and background values of magnetic
      susceptibility in the soil profile. These indicators were previously analyzed in
      the literature. The results showed that a range of correlation of magnetic
      susceptibility was significantly correlated with magnetic susceptibility measured
      at depths 1, 2, and 3 cm. It suggests that a range of correlation is a good
      measure of pollutants' dispersion in the soil profile. The sill of the variogram
      of magnetic susceptibility was found to be significantly correlated with the area
      under the curve of plot of magnetic susceptibility that is related to the soil
      pollution. In consequence, the parameters of microscale spatial variability of
      magnetic susceptibility in s soil profile are important measures that take into
      consideration the spatial aspect of s soil pollution.

PMID- 25960580
TI  - Degradation of Iodinated Contrast Media in Aquatic Environment by Means of UV,
      UV/TiO2 Process, and by Activated Sludge.
AB  - Iodinated contrast media (ICM), which are used for radiological visualization of
      human tissue and cardiovascular system, are poorly biodegradable; hence, new
      methods of their removal are sought. In this study, the effectiveness of selected
      X-ray ICM removal by means of UV and UV/TiO2 pretreatment processes from
      synthetic hospital wastewater was demonstrated. The following compounds were
      investigated: iodipamide, iohexol, and diatrizoate. The experiments were as
      follows: (i) estimated susceptibility of the ICM to decay by UV radiation in
      different aquatic matrices, (ii) determined an optimal retention time of hospital
      wastewater in the UV reactor, (iii) determined optimum TiO2 concentration to
      improve the effectiveness of the UV pretreatment, and (iv) investigated removal
      of ICM by combination of the photochemical and biological treatment methods. The
      quantum yields of selected ICM decay in deionized water (pH = 7.0) were
      established as 0.006, 0.004, and 0.029 for iohexol, diatrizoate, and iodipamide,
      respectively. Furthermore, the experiments revealed that diatrizoate and iohexol
      removal in the UV/TiO2 process is more efficient than in UV process alone. For
      diatrizoate, the removal efficiency equaled to 40 and 30 %, respectively, and for
      iohexol, the efficiency was 38 and 27 %, respectively. No significant increase in
      iodipamide removal in UV and UV/TiO2 processes was observed (29 and 28 %,
      respectively). However, highest removal efficiency was demonstrated in synthetic
      hospital wastewater with the combined photochemical and biological treatment
      method. The removal of diatrizoate and iohexol increased to at least 90 %, and
      for iodipamide, to at least 50 %.

PMID- 25960581
TI  - A new fish-based multi-metric assessment index for cyprinid streams in the
      Iranian Caspian Sea Basin.
AB  - A major issue for water resource management is the assessment of environmental
      degradation of lotic ecosystems. The overall aim of this study is to develop a
      multi-metric fish index for the cyprinid streams of the Caspian Sea Basin (MMICS)
      in Iran. As species diversity and composition as well as population structure in
      the studied streams are different to other regions, there is a substantial need
      to develop a new fish index. We sampled fish and environmental data of 102 sites
      in medium sized streams. We analysed human pressures at different spatial scales
      and determined applicable fish metrics showing a response to human pressures. In
      total, five structural and functional types of metrics (i.e. biodiversity,
      habitat, reproduction, trophic level and water quality sensitivity) were
      considered. In addition, we used 29 criteria describing major anthropogenic human
      pressures at sampling sites and generated a regional pressure index (RPI) that
      accounted for potential effects of multiple human pressures. For the MMICS
      development, we first defined reference sites (least disturbed) and secondly
      quantified differences of fish metrics between reference and impaired sites. We
      used a Generalised Linear Model (GLM) to describe metric responses to natural
      environmental differences in least disturbed conditions. By including impaired
      sites, the residual distributions of these models described the response range of
      each metric to human pressures, independently of natural environmental influence.
      Finally, seven fish metrics showed the best ability to discriminate between
      impaired and reference sites. The multi-metric fish index performed well in
      discriminating human pressure classes, giving a significant negative linear
      response to a gradient of the RPI. These methods can be used for further
      development of a standardised monitoring tool to assess the ecological status and
      trends in biological condition for streams of the whole country, considering its
      complex and diverse geology and climate.

PMID- 25960582
TI  - Activity Coefficients at Infinite Dilution and Physicochemical Properties for
      Organic Solutes and Water in the Ionic Liquid 1-Ethyl-3-methylimidazolium
      trifluorotris(perfluoroethyl)phosphate.
AB  - New data of activity coefficients at infinite dilution, gamma13infinity, for 65
      different solutes including alkanes, alkenes, alkynes, cycloalkanes, aromatic
      hydrocarbons, alcohols, thiophene, ethers, ketones, aldehydes, esters and water
      in the ionic liquid 1-ethyl-3-methylimidazolium
      trifluorotris(perfluoroethyl)phosphate, were determined using inverse gas
      chromatography within the temperature range from 318.15 to 368.15 K. This is a
      continuation of our study of ionic liquids based on this anion. The results are
      compared with the other trifluorotris(perfluoroethyl)phosphate ionic liquids. The
      gamma13infinity values were used to calculate thermodynamic functions such as
      partial molar excess Gibbs energies [Formula: see text], enthalpies [Formula: see
      text] and entropies [Formula: see text] as well as gas-liquid partition
      coefficients of the solutes, KL. These values were used to determine the linear
      free energy relationship (LFER) system constants as a function of temperature.
      The selectivities at infinite dilution needed for some extraction problems were
      calculated and compared with literature data of ionic liquids based on the
      trifluorotris(perfluoroethyl)phosphate anion and the 1-ethyl-3-methylimidazolium
      cation. Additionally, the density and viscosity of the investigated ionic liquid
      at temperatures from 298.15 to 348.15 K were measured.

PMID- 25960583
TI  - SO2 Solvation in the 1-Ethyl-3-Methylimidazolium Thiocyanate Ionic Liquid by
      Incorporation into the Extended Cation-Anion Network.
AB  - We have carried out an ab initio molecular dynamics study on the sulfur dioxide
      (SO2) solvation in 1-ethyl-3-methylimidazolium thiocyanate for which we have
      observed that both cations and anions play an essential role in the solvation of
      SO2. Whereas, the anions tend to form a thiocyanate- and much less often an
      isothiocyanate-SO2 adduct, the cations create a "cage" around SO2 with those
      groups of atoms that donate weak interactions like the alkyl hydrogen atoms as
      well as the heavy atoms of the [Formula: see text]-system. Despite these
      similarities between the solvation of SO2 and CO2 in ionic liquids, an essential
      difference was observed with respect to the acidic protons. Whereas CO2 avoids
      accepting hydrogen bonds form the acidic hydrogen atoms of the cations, SO2 can
      from O(SO2)-H(cation) hydrogen bonds and thus together with the strong anion
      adduct it actively integrates in the hydrogen bond network of this particular
      ionic liquid. The fact that SO2 acts in this way was termed a linker effect by
      us, because the SO2 can be situated between cation and anion operating as a
      linker between them. The particular contacts are the H(cation)[Formula: see
      text]O(SO2) hydrogen bond and a S(anion)-S(SO2) sulfur bridge. Clearly, this
      observation provides a possible explanation for the question of why the SO2
      solubility in these ionic liquids is so high.

PMID- 25960584
TI  - Need for achievement moderates the effect of motive-relevant challenge on
      salivary cortisol changes.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis plays a key role in the
      physiological response to stress, preparing the organism for appropriate action.
      While some research has examined universally relevant threats, other research has
      suggested that individual differences may moderate the relationship between
      stress and cortisol release, such that some individuals exhibit modified
      reactivity to personally relevant stressors or challenges. In the present study
      we investigated whether one individual difference-the implicit need for
      achievement-moderates the effect of motive-relevant challenge on salivary
      cortisol. Participants' salivary cortisol and felt affect were measured before
      and after engagement in an achievement task. In the positive- and no-feedback
      conditions, individuals high in implicit achievement motivation demonstrated
      increased cortisol response to the task, whereas in the negative feedback
      condition, individuals high in implicit achievement motivation demonstrated a
      dampened cortisol response. Furthermore, changes in cortisol were accompanied by
      changes in felt affect in the same direction, specifically hedonic tone. These
      results suggest that the HPA axis also responds to non-social-evaluative
      challenge in a personality-contingent manner.

PMID- 25960585
TI  - Cultural Adaptation and Implementation of Evidence-Based Parent-Training: A
      Systematic Review and Critique of Guiding Evidence.
AB  - With advances in knowledge regarding efficacious evidence-based interventions,
      there have been significant attempts to culturally adapt, implement, and
      disseminate parent training interventions broadly, especially across ethnic and
      cultural groups. We sought to examine the extent to which researchers and
      developers of evidence-based parent training programs have used cultural
      adaptation models, tested implementation strategies, and evaluated implementation
      outcomes when integrating the interventions into routine care by conducting a
      systematic review of the literature for four evidence-based parent training
      interventions: Parent-Child Interaction Therapy (PCIT), The Incredible Years
      (IY), Parent Management Training-Oregon Model (PMTOTM), and the Positive
      Parenting Program (Triple P). A total of 610 articles across the four programs
      were identified. Of those, only eight documented a rigorous cultural adaptation
      process, and only two sought to test the effectiveness of implementation
      strategies by using rigorous research designs. Our findings suggest that there is
      much work to be done to move parent-training intervention research towards a more
      rigorous examination of cultural adaptation and implementation practices.

PMID- 25960586
TI  - Canine Comfort: Pet Affinity Buffers the Negative Impact of Ambivalence over
      Emotional Expression on Perceived Social Support.
AB  - This study evaluated pet affinity as a buffer between ambivalence over emotional
      expression (AEE) and social support. AEE occurs when one desires to express
      emotions but is reluctant to do so and is related to negative psychological
      outcomes. Individuals high in AEE may have difficulty receiving social support
      and thus may not gain accompanying benefits. Social support has been associated
      with positive health outcomes, and pet support is positively associated with
      human social support. The present study explores the potential protective effect
      of pet affinity. One hundred ninety-eight undergraduate dog owners completed
      measures assessing perceived social support, pet affinity, and AEE. AEE was
      expected to be negatively associated with social support, and pet affinity was
      expected to buffer the negative effects of AEE on social support. We found that
      AEE was negatively associated with perceived social support. An interaction
      between pet affinity and AEE emerged such that the negative association between
      AEE and social support was weaker among those higher in pet affinity. Thus, at
      high levels of AEE, those who felt a close connection with their pets reported
      more perceived social support than those less connected with their pets. Overall,
      these findings emphasize the potential benefits of pet affinity.

PMID- 25960587
TI  - A Genetic Variant (COMT) Coding Dopaminergic Activity Predicts Personality Traits
      in Healthy Elderly.
AB  - Association studies between the NEO five factor personality inventory and COMT
      rs4680 have focused on young adults and the results have been inconsistent.
      However, personality and cortical changes with age may put older adults in a more
      sensitive range for detecting a relationship. The present study examined
      associations of COMT rs4680 and personality in older adults. Genetic association
      analyses were carried out between the NEO and the targeted COMT rs4680 in a
      large, well-characterized sample of healthy, cognitively normal older adults (N =
      616, mean age = 69.26 years). Three significant associations were found:
      participants with GG genotype showed lower mean scores on Neuroticism (p = 0.039)
      and higher scores on Agreeableness (p = 0.020) and Conscientiousness (p = 0.006)
      than participants with AA or AG genotypes. These results suggest that older
      adults with higher COMT enzymatic activity (GG), therefore lower dopamine level,
      have lower Neuroticism scores, and higher Agreeableness and Conscientiousness
      scores. This is consistent with a recent model of phasic and tonic dopamine
      release suggesting that even though GG genotype is associated with lower tonic
      dopamine release, the phasic release of dopamine might be optimal for a more
      adaptive personality profile.

PMID- 25960588
TI  - Parental Involvement, Child Temperament, and Parents' Work Hours: Differential
      Relations for Mothers and Fathers.
AB  - This study examined how child temperament was related to parents' time spent
      accessible to and interacting with their 2-year-olds. Bivariate analyses
      indicated that both fathers and mothers spent more time with temperamentally
      challenging children than easier children on workdays, but fathers spent less
      time with challenging children than easier children on non-workdays. After
      accounting for work hours, some associations between temperament and fathers'
      workday involvement dropped to non-significance. For fathers, work hours also
      moderated the relation between irregular temperament and workday play. For
      mothers, work hours moderated the relation between both difficult and irregular
      temperament and workday interaction. Mothers also spent more time with girls (but
      not boys) who were temperamentally irregular. Results speak to the influence of
      child temperament on parenting behavior, and the differential construction of
      parenting roles as a function of child characteristics and patterns of work.

PMID- 25960590
TI  - Diagnostic implications of an elevated troponin in the emergency department.
AB  - OBJECTIVE: To determine the proportion of initial troponin (cTn) elevations
      associated with Type I MI versus other cardiovascular and noncardiovascular
      diagnoses in an emergency department (ED) and whether or not a relationship
      exists between the cTn level and the likelihood of Type I MI. BACKGROUND: In the
      ED, cTn is used as a screening test for myocardial injury. However, the
      differential diagnosis for an initial positive cTn result is not clear. METHODS:
      Hospital medical records were retrospectively reviewed for visits associated with
      an initial positive troponin I-ultra (cTnI), >=0.05 MUg/L. Elevated cTnI levels
      were stratified into low (0.05-0.09), medium (0.1-0.99), or high (>=1.0).
      Discharge diagnoses were classified into 3 diagnostic groups (Type I MI, other
      cardiovascular, or noncardiovascular). RESULTS: Of 23,731 ED visits, 4,928 (21%)
      had cTnI testing. Of those tested, 16.3% had initial cTnI >=0.05. Among those
      with elevated cTn, 11% were classified as Type I MI, 34% had other cardiovascular
      diagnoses, and 55% had a noncardiovascular diagnosis. Type I MI was more common
      with high cTnI levels (41% incidence) than among subjects with medium (9%) or low
      (6%). CONCLUSION: A positive cTn is most likely a noncardiovascular diagnosis,
      but Type I MI is far more common with cTnI levels >=1.0.

PMID- 25960589
TI  - Cross-domain influences on youth risky driving behaviors: A developmental cascade
      analysis.
AB  - We apply a developmental cascade approach to study the longitudinal, cross-domain
      effects of negative family influence, deviant peer associations, and individual
      substance use on risky driving among a sample of low-income African American
      youth. Participants (N = 681) were followed from age 16 to age 21. Using
      structural equation modeling, we examined conceptual models of pathways to risky
      driving. Results indicated strong associations between domains within time points
      among negative family environment, deviant peer associations, individual
      substance use, and risky driving. Deviant peer associations were related to
      future risky driving. Alcohol and marijuana use also predicted later deviant peer
      relationships. The pathways were observed both between age 16 and 18 and between
      age 18 and 21. Consistent with the cascade hypotheses, we found that risks in one
      domain manifested as risks in the same domain across time in addition to
      spreading to other domains.

PMID- 25960591
TI  - Cardiac biomarkers.

PMID- 25960592
TI  - Short communication: Relationship between urinary neutrophil gelatinase
      associated lipocalin and noninfectious pyuria in dogs.
AB  - Neutrophil gelatinase-associated lipocalin (NGAL) is a neutrophil-derived protein
      whose concentration increases in plasma and urine with ongoing renal damage.
      Urinary leucocytes can be a potential source of urinary NGAL. The aim of this
      study is to investigate the effects of urinary neutrophil count and other urinary
      parameters on urinary NGAL values in urine with negative culture. Urinalysis,
      urine culture, and determination of urinary NGAL were performed on 33 clinically
      healthy nonproteinuric dogs with negative urinoculture. The median uNGAL
      concentration in dogs in this study population was 9.74 ng/mL (IQR 1.93-25.43
      ng/mL). In samples with WBCs > 5 hpf (mean 15.9, 6-50 leucocytes/hpf), median
      uNGAL value was significantly higher than that in samples with WBCs < 5 hpf (mean
      0.9, 0-3 leucocytes/hpf), (4.96 pg/mL (0.29-11.34) and 23.65 pg/mL (20.04-29.80),
      resp.; P = 0.0053). The severity of urinary pyuria and the UPC value were
      correlated with uNGAL concentration. The results of our study show that urinary
      NGAL concentration is correlated with WBCs number in urinary sediment of dogs
      with negative urinoculture. The present study suggests that noninfectious pyuria
      is significantly correlated with urinary NGAL values and might influence uNGAL
      values. 

PMID- 25960593
TI  - Association between plasma fibrinogen levels and mortality in acute-on-chronic
      hepatitis B liver failure.
AB  - Acute-on-chronic liver failure (AoCLF) is the most common type of liver failure
      and is associated with high mortality. Fibrinogen is critical in maintaining
      primary and secondary hemostasis. Therefore, we prospectively analyzed the
      association between fibrinogen and outcomes in AoCLF patients. Plasma fibrinogen
      was measured in 169 AoCLF, 173 chronic hepatitis B (CHB), and 171 healthy
      patients using a coagulation method. The predictive ability of fibrinogen for 3
      month mortality in AoCLF patients was assessed using receiver operating
      characteristic (ROC) curve and multivariable logistic regression analyses. Plasma
      fibrinogen was significantly lower in nonsurvivor AoCLF patients compared with
      survivor AoCLF, CHB, and control patients. The sensitivity, specificity, and area
      under the ROC curve of 1/fibrinogen predicting mortality in AoCLF patients were
      66.7%, 72.5%, and 0.746 (95% confidence interval (CI): 0.672-0.820, P < 0.001),
      and the fibrinogen cutoff value was 0.90 g/L. On multivariate logistic regression
      analysis, low fibrinogen was an independent factor predicting mortality (odds
      ratio: 0.304; 95% CI: 0.094-0.983; P = 0.047). Nonsurvivor AoCLF patients had
      significantly decreased fibrinogen levels, suggesting that low plasma fibrinogen
      may be a useful predictor of poor prognosis in AoCLF patients. 

PMID- 25960594
TI  - NT-proBNP as early marker of subclinical late cardiotoxicity after doxorubicin
      therapy and mediastinal irradiation in childhood cancer survivors.
AB  - BACKGROUND: Childhood cancer survivors treated with anthracyclines and
      mediastinal irradiation are at risk for late onset cardiotoxicity. AIMS OF THE
      STUDY: To assess the role of N-terminal pro-brain natriuretic peptide (NT-proBNP)
      and tissue Doppler imaging (TDI) as early predictors of late onset cardiotoxicity
      in asymptomatic survivors of childhood cancer treated with doxorubicin with or
      without mediastinal irradiation. METHODS: A cross-sectional study on 58
      asymptomatic survivors of childhood cancer who received doxorubicin in their
      treatment protocols and 32 asymptomatic Hodgkin's lymphoma survivors who received
      anthracycline and mediastinal irradiation. Levels of NT-proBNP, TDI, and
      conventional echocardiography were determined. RESULTS: Thirty percent of
      survivors had abnormal NT-proBNP levels. It was significantly related to age at
      diagnosis, duration of follow-up, and cumulative dose of doxorubicin. TDI
      detected myocardial affection in 20% more than conventional echocardiography.
      Furthermore, abnormalities in TDI and NT-pro-BNP levels were more common in
      Hodgkin lymphoma survivors receiving both chemotherapy and radiotherapy.
      CONCLUSIONS: TDI could detect early cardiac dysfunction even in those with normal
      conventional echocardiography. Measurement of NT-proBNP represents an interesting
      strategy for detecting subclinical cardiotoxicity. We recommend prospective and
      multicenter studies to validate the role of NT-proBNP as an early marker for late
      onset doxorubicin-induced cardiotoxicity.

PMID- 25960595
TI  - Evaluation of high sensitive troponin in erectile dysfunction.
AB  - BACKGROUND: Evidence is accumulating in favour of a link between erectile
      dysfunction (ED) and coronary artery diseases. We investigated the presence of
      cardiac injury in patients who have had arteriogenic and nonarteriogenic ED using
      the hs-Tn levels. METHODS: The diagnosis of ED was based on the International
      Index of Erectile Function 5-questionnaire (IIF-5) and patients were classified
      as arteriogenic (A-ED, n = 40), nonarteriogenic (NA-ED, n = 48), and borderline
      (BL-ED, n = 32) patients in relation to the results of echo-color-Doppler
      examination of cavernous arteries. The level of hs-TnT and hs-TnI was measured in
      120 men with a history of ED of less than one year with no clinical evidence of
      cardiac ischemic disease. RESULTS: The levels of both hs-TnT and hs-TnI were
      within the reference range and there was no significant (P > 0.05) difference
      between patients of the three groups. The hs-CRP values were higher in A-ED men
      compared with NA-ED (P = 0.048) but not compared with BL-ED (P = 0.136) and
      negatively correlated with IIF-5 (r = -0.480; P = 0.031). CONCLUSIONS: In ED
      patients of the three groups the measurement of hs-Tn allows us to exclude the
      presence of cardiac involvement at least when the history of ED is less than one
      year and the men are without atherosclerotic risk factors.

PMID- 25960597
TI  - Prognostic value of galectin-3 in patients with heart failure.
AB  - Galectins are a family of soluble beta-galactoside-binding lectins that have
      important role in inflammation, immunity, and cancer. Galectin-3 as a part of
      this lectin family plays a very important role in development of heart failure.
      According to recent papers, galectin-3 plasma level correlates with heart failure
      outcome, primarily with rehospitalisation and death from heart failure. This
      paper summarizes the most recent advances in galectin-3 research, with the accent
      on the role of galectin-3 in pathophysiology of myocardial remodelling and heart
      failure development--with preserved and reduced ejection fraction, and some
      implication on development of new disease modifying drugs.

PMID- 25960596
TI  - Copeptin testing in acute myocardial infarction: ready for routine use?
AB  - Suspected acute myocardial infarction is one of the leading causes of admission
      to emergency departments. In the last decade, biomarkers revolutionized the
      management of patients with suspected acute coronary syndromes. Besides their
      pivotal assistance in timely diagnosis, biomarkers provide additional information
      for risk stratification. Cardiac troponins I and T are the most sensitive and
      specific markers of acute myocardial injury. Nonetheless, in order to overcome
      the remaining limitations of these markers, novel candidate biomarkers sensitive
      to early stage of disease are being extensively investigated. Among them,
      copeptin, a stable peptide derived from the precursor of vasopressin, emerged as
      a promising biomarker for the evaluation of suspected acute myocardial
      infarction. In this review, we summarize the currently available evidence for the
      usefulness of copeptin in the diagnosis and risk stratification of patients with
      suspected acute myocardial infarction in comparison with routine biomarkers. 

PMID- 25960599
TI  - Impact of magnetic field parameters and iron oxide nanoparticle properties on
      heat generation for use in magnetic hyperthermia.
AB  - Heating of nanoparticles (NPs) using an AC magnetic field depends on several
      factors, and optimization of these parameters can improve the efficiency of heat
      generation for effective cancer therapy while administering a low NP treatment
      dose. This study investigated magnetic field strength and frequency, NP size, NP
      concentration, and solution viscosity as important parameters that impact the
      heating efficiency of iron oxide NPs with magnetite (Fe3O4) and maghemite (gamma
      Fe2O3) crystal structures. Heating efficiencies were determined for each
      experimental setting, with specific absorption rates (SARs) ranging from 3.7 to
      325.9 W/g Fe. Magnetic heating was conducted on iron oxide NPs synthesized in our
      laboratories (with average core sizes of 8, 11, 13, and 18 nm), as well as
      commercially-available iron oxides (with average core sizes of 8, 9, and 16 nm).
      The experimental magnetic coil system made it possible to isolate the effect of
      magnetic field parameters and independently study the effect on heat generation.
      The highest SAR values were found for the 18 nm synthesized particles and the
      maghemite nanopowder. Magnetic field strengths were applied in the range of 15.1
      to 47.7 kA/m, with field frequencies ranging from 123 to 430 kHz. The best
      heating was observed for the highest field strengths and frequencies tested, with
      results following trends predicted by the Rosensweig equation. An increase in
      solution viscosity led to lower heating rates in nanoparticle solutions, which
      can have significant implications for the application of magnetic fluid
      hyperthermia in vivo.

PMID- 25960598
TI  - Biomarkers of hemodynamic stress and aortic stiffness after STEMI: a cross
      sectional analysis.
AB  - AIM: Increased aortic stiffness might adversely affect cardiac structure,
      function, and perfusion. Release of biomarkers of hemodynamic stress is thought
      to be enhanced by these alterations. We aimed to evaluate the association between
      biomarkers of hemodynamic stress and aortic stiffness assessed at a chronic stage
      after ST-segment elevation myocardial infarction (STEMI). METHODS: Fifty-four
      patients four months after STEMI were enrolled in this cross-sectional, single
      center study. N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional
      pro-A-type natriuretic peptide (MR-proANP), and mid-regional proadrenomedullin
      (MR-proADM) levels were measured by established assays. Aortic stiffness was
      assessed by the measurement of pulse wave velocity using phase-contrast
      cardiovascular magnetic resonance. RESULTS: NT-proBNP, MR-proANP, and MR-proADM
      concentrations were all correlated with aortic stiffness in univariate analysis
      (r = 0.378, r = 0.425, and r = 0.532; all P < 0.005, resp.). In multiple linear
      regression analysis, NT-proBNP (beta = 0.316, P = 0.005) and MR-proADM (beta =
      0.284, P < 0.020) levels were associated with increased aortic stiffness
      independently of age, blood pressure, and renal function. NT-proBNP was the
      strongest predictor for high aortic stiffness (area under the curve: 0.82, 95% CI
      0.67-0.96). CONCLUSION: At a chronic stage after STEMI, concentrations of
      biomarkers for hemodynamic stress, especially NT-proBNP, are positively
      correlated with aortic stiffness. These biomarkers might also be useful as
      predictors of high aortic stiffness after STEMI.

PMID- 25960600
TI  - Time for Transformation: Public Policy Must Change to Achieve Health Equity for
      LGBT Older Adults.
AB  - The marriage equality movement and the Affordable Care Act have enormous
      potential to reduce health disparities in LGBT elders, but more data and
      additional policy changes are sorely needed.

PMID- 25960601
TI  - Spectroscopic studies of nucleic acid additions during seed-mediated growth of
      gold nanoparticles.
AB  - The effect of adding nucleic acids to gold seeds during the growth stage of
      either nanospheres or nanorods was investigated using UV-Vis spectroscopy to
      reveal any oligonucleotide base or structure-specific effects on nanoparticle
      growth kinetics or plasmonic signatures. Spectral data indicate that the presence
      of DNA duplexes during seed ageing drastically accelerated nanosphere growth
      while the addition of single-stranded polyadenine at any point during seed ageing
      induces nanosphere aggregation. For seeds added to a gold nanorod growth
      solution, single-stranded polythymine induces a modest blue-shift in the
      longitudinal peak wavelength. Moreover, a particular sequence comprised of 50%
      thymine bases was found to induce a faster, more dramatic blue-shift in the
      longitudinal peak wavelength compared to any of the homopolymer incubation cases.
      Monomeric forms of the nucleic acids, however, do not yield discernable spectral
      differences in any of the gold suspensions studied.

PMID- 25960602
TI  - Patterns and Predictors of Service Use Among Women Who Have Separated from an
      Abusive Partner.
AB  - Using baseline data from a survey of 309 Canadian women recently separated from
      an abusive partner, we investigated patterns of access to health, social, legal,
      and violence-specific services and whether abuse history and social and health
      variables predict service use. We compared rates of service use to population
      rates, and used logistic regression to identify determinants of use. Service use
      rates were substantially higher than population estimates in every category,
      particularly in general and mental health sectors. Although women were confident
      in their ability to access services, they reported substantial unmet need,
      difficulty accessing services, and multiple barriers. The strongest unique
      predictors of use varied across service type. Health variables (high disability
      chronic pain, symptoms of depression and PTSD), low income, and mothering were
      the most consistent predictors. Service providers and policy makers must account
      for social location, abuse history, and health status of Intimate Violence (IPV)
      survivors. Strategies to enhance access to primary health care services, and to
      create a system of more integrated, accessible services, are required.

PMID- 25960603
TI  - Calixarene-Mediated Synthesis of Cobalt Nanoparticles: An Accretion Model for
      Separate Control over Nucleation and Growth.
AB  - The nucleation and growth of crystalline cobalt nanoparticles (Co NPs) under
      solvothermal conditions can be separated into distinct stages by using (i)
      polynuclear clusters with multivalent capping ligands to initiate nucleation, and
      (ii) thermolabile organometallic complexes with low autonucleation potential to
      promote crystalline growth. Both nucleation and growth take place within an
      amorphous accretion, formed in the presence of polyvalent surfactants. At the pre
      nucleation stage, a calixarene complex with multiple Co2-alkyne ligands (Co16
      calixarene 1) undergoes thermal decomposition above 130  degrees C to form
      "capped cluster" intermediates that coalesce into well-defined Co nanoclusters,
      but are resistant to further aggregation. At the post-nucleation stage, a monomer
      (pentyne-Co4(CO)10, or PTC) with a low thermal activation threshold but a high
      barrier to autonucleation is introduced, yielding epsilon-Co NPs with a linear
      relationship between particle volume and the Co mole ratio ([Cofinal]/[Coseed]).
      Co nanocrystals can be produced up to 40 nm with a 10-12% size dispersity within
      the accretion, but their growth rate depends on the activity of the supporting
      surfactant, with an octapropargyl calixarene derivative (OP-C11R) providing the
      most efficient transport of reactive Co species through the amorphous matrix.
      Post-growth digestion with oleic acid releases the Co NPs from the residual
      accretion, which can then self-assemble by magnetic dipolar interactions into
      flux-closure rings when stabilized by calixarene-based surfactants. These studies
      demonstrate that organometallic complexes can be designed to establish rational
      control over the nucleation and growth of crystalline NPs within an intermediate
      accretion phase.

PMID- 25960604
TI  - Identifying the Structure of the Intermediate, Li2/3CoPO4, Formed during
      Electrochemical Cycling of LiCoPO4.
AB  - In situ synchrotron diffraction measurements and subsequent Rietveld refinements
      are used to show that the high energy density cathode material LiCoPO4 (space
      group Pnma) undergoes two distinct two-phase reactions upon charge and discharge,
      both occurring via an intermediate Li2/3(Co2+)2/3(Co3+)1/3PO4 phase. Two
      resonances are observed for Li2/3CoPO4 with intensity ratios of 2:1 and 1:1 in
      the 31P and 7Li NMR spectra, respectively. An ordering of Co2+/Co3+ oxidation
      states is proposed within a (a * 3b * c) supercell, and Li+/vacancy ordering is
      investigated using experimental NMR data in combination with first-principles
      solid-state DFT calculations. In the lowest energy configuration, both the Co3+
      ions and Li vacancies are found to order along the b-axis. Two other low energy
      Li+/vacancy ordering schemes are found only 5 meV per formula unit higher in
      energy. All three configurations lie below the LiCoPO4-CoPO4 convex hull and they
      may be readily interconverted by Li+ hops along the b-direction.

PMID- 25960606
TI  - Bioinformatics and the developing world.

PMID- 25960605
TI  - Cu3-x P Nanocrystals as a Material Platform for Near-Infrared Plasmonics and
      Cation Exchange Reactions.
AB  - Synthesis approaches to colloidal Cu3P nanocrystals (NCs) have been recently
      developed, and their optical absorption features in the near-infrared (NIR) have
      been interpreted as arising from a localized surface plasmon resonance (LSPR).
      Our pump-probe measurements on platelet-shaped Cu3-x P NCs corroborate the
      plasmonic character of this absorption. In accordance with studies on crystal
      structure analysis of Cu3P dating back to the 1970s, our density functional
      calculations indicate that this material is substoichiometric in copper, since
      the energy of formation of Cu vacancies in certain crystallographic sites is
      negative, that is, they are thermodynamically favored. Also, thermoelectric
      measurements point to a p-type behavior of the majority carriers from films of
      Cu3-x P NCs. It is likely that both the LSPR and the p-type character of our Cu3
      x P NCs arise from the presence of a large number of Cu vacancies in such NCs.
      Motivated by the presence of Cu vacancies that facilitate the ion diffusion, we
      have additionally exploited Cu3-x P NCs as a starting material on which to probe
      cation exchange reactions. We demonstrate here that Cu3-x P NCs can be easily
      cation-exchanged to hexagonal wurtzite InP NCs, with preservation of the anion
      framework (the anion framework in Cu3-x P is very close to that of wurtzite InP).
      Intermediate steps in this reaction are represented by Cu3-x P/InP
      heterostructures, as a consequence of the fact that the exchange between Cu+ and
      In3+ ions starts from the peripheral corners of each NC and gradually evolves
      toward the center. The feasibility of this transformation makes Cu3-x P NCs an
      interesting material platform from which to access other metal phosphides by
      cation exchange.

PMID- 25960607
TI  - Stereoselective Synthesis of Dioxolanes and Oxazolidines via a Desymmetrization
      Acetalization/Michael Cascade.
AB  - The desymmetrization of p-quinols using a Bronsted acid catalyzed
      acetalization/Michael cascade was achieved in high yields and
      diastereoselectivities for aldehydes and imines. Use of a chiral Bronsted acid
      allowed for the synthesis of 1,3-dioxolane and 1,3-oxazolidine products in modest
      enantioselectivity.

PMID- 25960608
TI  - 'To[o] much eating stifles the child': fat bodies and reproduction in early
      modern England .
AB  - This article examines associations between fat bodies and reproductive
      dysfunction that were prevalent in medical, midwifery and other literature in
      early modern England. In a period when fertility and successful reproduction were
      regarded as hugely important for social, economic and political stability such
      associations further contributed to negative attitudes towards fat bodies that
      were fuelled by connection with the vices of sloth and gluttony. Fat bodies were
      categorized as inherently, constitutionally, less sexual and reproductively
      successful. Consequently they were perceived as unhealthy and unfit for their
      primary purpose once they had reached sexual maturity: marriage and the
      production of children. 

PMID- 25960609
TI  - Feasibility and safety of continuous and chronic bilateral deep brain stimulation
      of the medial forebrain bundle in the naive Sprague-Dawley rat.
AB  - OBJECTIVE: Deep brain stimulation (DBS) of the superolateral branch of the medial
      forebrain bundle (MFB) has provided rapid and dramatic reduction of depressive
      symptoms in a clinical trial. Early intracranial self-stimulation experiments of
      the MFB suggested detrimental side effects on the animals' health; therefore, the
      current study looked at the viability of chronic and continuous MFB-DBS in
      rodents, with particular attention given to welfare issues and identification of
      stimulated pathways. METHODS: Sprague-Dawley female rats were submitted to
      stereotactic microelectrode implantation into the MFB. Chronic continuous DBS was
      applied for 3-6 weeks. Welfare monitoring and behavior changes were assessed.
      Postmortem histological analysis of c-fos protein expression was carried out.
      RESULTS: MFB-DBS resulted in mild and temporary weight loss in the animals, which
      was regained even with continuing stimulation. MFB-DBS led to increased and long
      lasting c-fos expression in target regions of the mesolimbic/mesocortical system.
      CONCLUSIONS: Bilateral continuous chronic MFB-DBS is feasible, safe, and without
      impact on the rodent's health. MFB-DBS results in temporary increase in
      exploration, which could explain the initial weight loss, and does not produce
      any apparent behavioral abnormalities. This platform represents a powerful tool
      for further preclinical investigation of the MFB stimulation in the treatment of
      depression.

PMID- 25960610
TI  - The Developmental Progression of Understanding of Mind during a Hiding Game.
AB  - In this longitudinal study, 52 typically developing preschoolers engaged in a
      hiding game with their mothers when children were 42-, 54-, and 66-months old.
      Children's understanding of mind, positive affect, and engagement with the task
      were rated, and mothers' utterances were coded for role and content. Analyses
      confirmed that some facets of children's understanding of mind developed
      sequentially; specifically, they expressed an understanding of knowledge access
      before an understanding of deception and false beliefs, and expressed an
      understanding of deception before an understanding of false beliefs. Children's
      understanding of mind increased across visits and positively correlated with
      false belief task performance. Results suggest that mothers may tailor the
      content of their utterances to the child's growing expertise, but the role of
      mothers' utterances did not change. Observing preschoolers engaged in a playful
      hiding game revealed that children's understanding of mind not only increased
      with age but also developed sequentially.

PMID- 25960611
TI  - Positive reinforcement training as enrichment for singly housed rhesus macaques
      (Macaca mulatta).
AB  - Positive reinforcement training is one component of behavioural management
      employed to improve psychological well-being. There has been regulatory promotion
      to compensate for restricted social housing in part by providing human
      interaction to singly caged primates, implying an efficacy standard for
      evaluating human interaction. The effect of positive reinforcement training on
      the behaviour of 61 singly housed laboratory rhesus macaques (Macaca mulatta) was
      evaluated at two large primate facilities. Training involved body part
      presentation and basic control behaviours. Baseline data were compared to two
      treatment phases presented in varying order across individuals, six minutes per
      week of positive reinforcement training and six minutes per week of unstructured
      human interaction. While a MANOVA involving behavioural categories and study
      conditions across study subjects was significant, univariate ANOVAs found no
      effect of phase within any behavioural category. Categorising subjects according
      to rearing, housing facility, or baseline levels of abnormal behaviour did not
      reveal changes in behaviour with positive reinforcement training or human
      interaction. This study failed to detect, to any degree, the types of behavioural
      changes documented in the scientific literature to result from pairing singly
      housed monkeys. Implementing short durations of positive reinforcement training
      across large numbers of singly housed animals may not be the most effective
      manner for incorporating positive reinforcement training in the behavioural
      management of laboratory macaques. Rather, directing efforts toward individuals
      with specific behavioural, management, clinical, research or therapeutic needs
      may represent a more fruitful approach to improving psychological well-being with
      this technique.

PMID- 25960612
TI  - Activation of vitamin D regulates response of human bronchial epithelial cells to
      Aspergillus fumigatus in an autocrine fashion.
AB  - Aspergillus fumigatus (A. fumigatus) is one of the most common fungi to cause
      diseases in humans. Recent evidence has demonstrated that airway epithelial cells
      play an important role in combating A. fumigatus through inflammatory responses.
      Human airway epithelial cells have been proven to synthesize the active vitamin
      D, which plays a key role in regulating inflammation. The present study was
      conducted to investigate the impact of A. fumigatus infection on the activation
      of vitamin D and the role of vitamin D activation in A. fumigatus-elicited
      antifungal immunity in normal human airway epithelial cells. We found that A.
      fumigatus swollen conidia (SC) induced the expression of 1alpha-hydroxylase, the
      enzyme catalyzing the synthesis of active vitamin D, and vitamin D receptor (VDR)
      in 16HBE cells and led to increased local generation of active vitamin D. Locally
      activated vitamin D amplified SC-induced expression of antimicrobial peptides in
      16HBE cells but attenuated SC-induced production of cytokines in an autocrine
      fashion. Furthermore, we identified beta-glucan, the major A. fumigatus cell wall
      component, as the causative agent for upregulation of 1alpha-hydroxylase and VDR
      in 16HBE cells. Therefore, activation of vitamin D is inducible and provides a
      bidirectional regulation of the responses to A. fumigatus in 16HBE cells. 

PMID- 25960613
TI  - Astragaloside IV inhibits NF- kappa B activation and inflammatory gene expression
      in LPS-treated mice.
AB  - In this study we investigated the role of astragaloside IV (AS-IV), one of the
      major active constituents purified from the Chinese medicinal herb Astragalus
      membranaceus, in LPS-induced acute inflammatory responses in mice in vivo and
      examined possible underlying mechanisms. Mice were assigned to four groups:
      vehicle-treated control animals; AS-IV-treated animals (10 mg/kg b.w. AS-IV daily
      i.p. injection for 6 days); LPS-treated animals; and AS-IV plus LPS-treated
      animals. We found that AS-IV treatment significantly inhibited LPS-induced
      increases in serum levels of MCP-1 and TNF by 82% and 49%, respectively. AS-IV
      also inhibited LPS-induced upregulation of inflammatory gene expression in
      different organs. Lung mRNA levels of cellular adhesion molecules, MCP-1,
      TNFalpha, IL-6, and TLR4 were significantly attenuated, and lung neutrophil
      infiltration and activation were strongly inhibited, as reflected by decreased
      myeloperoxidase content, when the mice were pretreated with AS-IV. Similar
      results were observed in heart, aorta, kidney, and liver. Furthermore, AS-IV
      significantly suppressed LPS-induced NF-kappaB and AP-1 DNA-binding activities in
      lung and heart. In conclusion, our data provide new in vivo evidence that AS-IV
      effectively inhibits LPS-induced acute inflammatory responses by modulating NF
      kappaB and AP-1 signaling pathways. Our results suggest that AS-IV may be useful
      for the prevention or treatment of inflammatory diseases. 

PMID- 25960614
TI  - Ginkgo biloba extract improves insulin signaling and attenuates inflammation in
      retroperitoneal adipose tissue depot of obese rats.
AB  - Due to the high incidence and severity of obesity and its related disorders, it
      is highly desirable to develop new strategies to treat or even to prevent its
      development. We have previously described that Ginkgo biloba extract (GbE)
      improved insulin resistance and reduced body weight gain of obese rats. In the
      present study we aimed to evaluate the effect of GbE on both inflammatory cascade
      and insulin signaling in retroperitoneal fat depot of diet-induced obese rats.
      Rats were fed with high fat diet for 2 months and thereafter treated for 14 days
      with 500 mg/kg of GbE. Rats were then euthanized and samples from retroperitoneal
      fat depot were used for western blotting, RT-PCR, and ELISA experiments. The GbE
      treatment promoted a significant reduction on both food/energy intake and body
      weight gain in comparison to the nontreated obese rats. In addition, a
      significant increase of both Adipo R1 and IL-10 gene expressions and IR and Akt
      phosphorylation was also observed, while NF-kappaB p65 phosphorylation and TNF
      alpha levels were significantly reduced. Our data suggest that GbE might have
      potential as a therapy to treat obesity-related metabolic diseases, with special
      interest to treat obese subjects resistant to adhere to a nutritional education
      program. 

PMID- 25960615
TI  - Anti-inflammatory and immunoregulatory functions of artemisinin and its
      derivatives.
AB  - Artemisinin and its derivatives are widely used in the world as the first-line
      antimalarial drug. Recently, growing evidences reveal that artemisinin and its
      derivatives also possess potent anti-inflammatory and immunoregulatory
      properties. Meanwhile, researchers around the world are still exploring the
      unknown bioactivities of artemisinin derivatives. In this review, we provide a
      comprehensive discussion on recent advances of artemisinin derivatives affecting
      inflammation and autoimmunity, the underlying molecular mechanisms, and also drug
      development of artemisinins beyond antimalarial functions. 

PMID- 25960616
TI  - Decrease in circulating dendritic cell precursors in patients with peripheral
      artery disease.
AB  - Peripheral artery disease (PAD) is a common manifestation of atherosclerosis.
      Inflammation is important for initiation and progression of the disease.
      Dendritic cells (DCs) as antigen-presenting cells play an important role in the
      immune system. Therefore, we hypothesize that, in patients with PAD, DCPs might
      be reduced in blood due to their recruitment into the vascular wall and induce a
      proinflammatory response. The numbers of myeloid DCPs, plasmacytoid DCPs, and
      total DCPs were analyzed by flow cytometry in blood of patients with PAD (n = 52)
      compared to controls (n = 60). Femoralis plaques (n = 12) of patients who
      underwent surgery were immunostained for CD209 and CD83 (mDCs) as well as CD304,
      CD123 (pDCs), and HLA-DR. In patients with PAD, a significant decrease in mDCPs,
      pDCPs, and tDCPs was observed. In immunostaining, markers indicative for mDCs
      (CD209: 16 versus 8 cells/0.1 mm(2), P = 0.02; CD83: 19 versus 5 cells/0.1 mm(2),
      P = 0.03) were significantly elevated in femoralis plaques compared to control
      vessels. We show for the first time that mDCPs, pDCPs, and tDCPs are
      significantly reduced in patients with PAD. Immunohistochemical analysis
      unraveled that the decrease in DCPs might be due to their recruitment into
      atherosclerotic plaques. 

PMID- 25960617
TI  - Construction, expression, and characterization of a recombinant immunotoxin
      targeting EpCAM.
AB  - Epithelial cell adhesion molecule (EpCAM) is a type I transmembrane glycoprotein
      overexpressed in human epithelioma but with relatively low expression in normal
      epithelial tissues. To exploit this differential expression pattern for targeted
      cancer therapy, an EpCAM-targeted immunotoxin was developed and its antitumor
      activity was investigated in vitro. An immunotoxin (scFv2A9-PE or APE) was
      constructed by genetically fusing a truncated form (PE38KDEL) of Pseudomonas
      aeruginosa exotoxin with an anti-EpCAM single-chain variable fragment (scFv).
      ELISA and flow cytometry were performed to verify immunotoxin (scFv2A9-PE or APE)
      antigen-binding activity with EpCAM. Cytotoxicity was measured by MTT assay.
      Confocal microscopy was used to observe its cellular localization. The results of
      ELISA and flow cytometry revealed that the immunotoxin efficiently recognized
      recombinant and natural EpCAM. Its antigen-binding activity was relatively lower
      than 2A9. MTT assay confirmed potent reduction in EpCAM-positive HHCC (human
      hepatocellular carcinoma) cell viability (IC50 50 pM). Immunofluorescence
      revealed that the immunotoxin localized to endoplasmic reticulum 24 h later. In
      conclusion, we described the development of an EpCAM-targeted immunotoxin with
      potent activity against tumor cells, which may lay the foundation for future
      development of therapeutic antibody for the treatment of EpCAM-positive tumors. 

PMID- 25960618
TI  - Inhibitory effect of methyleugenol on IgE-mediated allergic inflammation in RBL
      2H3 cells.
AB  - Allergic diseases, such as asthma and allergic rhinitis, are common. Therefore,
      the discovery of therapeutic drugs for these conditions is essential.
      Methyleugenol (ME) is a natural compound with antiallergic, antianaphylactic,
      antinociceptive, and anti-inflammatory effects. This study examined the
      antiallergic effect of ME on IgE-mediated inflammatory responses and its
      antiallergy mechanism in the mast cell line, RBL-2H3. We found that ME
      significantly inhibited the release of beta-hexosaminidase, tumor necrosis factor
      (TNF-) alpha, and interleukin- (IL-) 4, and was not cytotoxic at the tested
      concentrations (0-100 MUM). Additionally, ME markedly reduced the production of
      the proinflammatory lipid mediators prostaglandin E2 (PGE2), prostaglandin D2
      (PGD2), leukotriene B4 (LTB4), and leukotriene C4 (LTC4). We further evaluated
      the effect of ME on the early stages of the FcepsilonRI cascade. ME significantly
      inhibited Syk phosphorylation and expression but had no effect on Lyn.
      Furthermore, it suppressed ERK1/2, p38, and JNK phosphorylation, which is
      implicated in proinflammatory cytokine expression. ME also decreased cytosolic
      phospholipase A2 (cPLA2) and 5-lipoxygenase (5-LO) phosphorylation and
      cyclooxygenase-2 (COX-2) expression. These results suggest that ME inhibits
      allergic response by suppressing the activation of Syk, ERK1/2, p38, JNK, cPLA2,
      and 5-LO. Furthermore, the strong inhibition of COX-2 expression may also
      contribute to the antiallergic action of ME. Our study provides further
      information about the biological functions of ME. 

PMID- 25960619
TI  - Percentages of CD4+CD161+ and CD4-CD8-CD161+ T cells in the synovial fluid are
      correlated with disease activity in rheumatoid arthritis.
AB  - OBJECTIVE: CD161 has been identified as a marker of human IL-17-producing T cells
      that are implicated in the pathogenesis of rheumatoid arthritis (RA). This study
      aimed to investigate the potential link between the percentage of CD161+ T cells
      and disease activity in RA patients. METHODS: Peripheral blood (PB) from 54 RA
      patients and 21 healthy controls was evaluated. Paired synovial fluid (SF) (n =
      17) was analyzed. CD161 expression levels on CD4+, CD8+, and CD4-CD8- T cells
      were assessed by flow cytometry. RESULTS: The percentage of CD4+CD161+ T cells in
      RA SF was higher than RA PB, and it was positively correlated with DAS28,
      erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). CD4-CD8
      CD161+ T cell percentage was decreased in RA PB and was further reduced in RA SF,
      and its level in SF was inversely correlated with DAS28, ESR, and CRP. However,
      CD8+CD161+ T cell percentage was neither changed in RA PB and SF nor correlated
      with disease activity indices. CONCLUSION: An increased CD4+CD161+ T cell
      percentage and a decreased CD4-CD8-CD161+ T cell percentage are present in RA SF
      and are associated with disease activity, and the accumulation of CD4+CD161+ T
      cells in SF may contribute to the local inflammation of RA.

PMID- 25960620
TI  - The evaluation of plasma and leukocytic IL-37 expression in early inflammation in
      patients with acute ST-segment elevation myocardial infarction after PCI.
AB  - OBJECTIVE: Acute ST-segment elevation myocardial infarction (ASTEMI) is
      accompanied by increased expression of inflammation and decreased expression of
      anti-inflammation. IL-37 was found to be involved in the atherosclerosis-related
      diseases and increased in acute coronary syndrome. However, the level of IL-37 in
      blood plasma and leukocytes from patients with ASTEMI after percutaneous coronary
      intervention (PCI) has not been explored. METHODS: We collected peripheral venous
      blood from consented patients at 12 h, 24 h, and 48 h after PCI and healthy
      volunteers. Plasma IL-37, IL-18, IL-18-binding protein (BP), and high sensitive C
      reaction protein (hs-CRP) were quantified by ELISA and leukocytic IL-37 and ICAM
      1 by immunoblotting. RESULTS: Plasma IL-37, IL-18, and IL-18 BP expression
      decreased compared to those in healthy volunteers while hs-CRP level was high.
      Both leukocytic IL-37 and ICAM-1 were highest expressed at 12 h point but
      significantly decreased at 48 h point. CONCLUSION: These findings suggest L-37
      does not play an important role in the systematic inflammatory response but may
      be involved in leukocytic inflammation in ASTEMI after PCI.

PMID- 25960622
TI  - The combination of N-acetyl cysteine, alpha-lipoic acid, and bromelain shows high
      anti-inflammatory properties in novel in vivo and in vitro models of
      endometriosis.
AB  - To evaluate the efficacy of an association of N-acetyl cystein, alpha-lipoic
      acid, and bromelain (NAC/LA/Br) in the treatment of endometriosis we set up a new
      in vivo murine model. We explored the anti-inflammatory and proapoptotic effect
      of this combination on human endometriotic endothelial cells (EECs) and on
      endothelial cells isolated from normal uterus (UtMECs). We implanted fragments of
      human endometriotic cysts intraperitoneally into SCID mice to evaluate the
      efficacy of NAC/LA/Br treatment. UtMECs and EECs, untreated or treated with
      NAC/LA/Br, were activated with the proinflammatory stimulus TNF-alpha and their
      response in terms of VCAM1 expression was evaluated. The proapoptotic effect of
      higher doses of NAC/LA/Br on UtMECs and EECs was measured with a fluorogenic
      substrate for activated caspases 3 and 7. The preincubation of EECs with
      NAC/LA/Br prior to cell stimulation with TNF-alpha prevents the upregulation of
      the expression of the inflammatory "marker" VCAM1. Furthermore NAC/LA/Br were
      able to induce EEC, but not UtMEC, apoptosis. Finally, the novel mouse model
      allowed us to demonstrate that mice treated with NAC/LA/Br presented a lower
      number of cysts, smaller in size, compared to untreated mice. Our findings
      suggest that these dietary supplements may have potential therapeutic uses in the
      treatment of chronic inflammatory diseases like endometriosis. 

PMID- 25960623
TI  - Dialogic Reading's Potential to Improve Children's Emergent Literacy Skills and
      Behavior.
AB  - Young children entering school with poor oral vocabulary skills may be "doubly
      disadvantaged." Their poor oral vocabulary skills will likely impede their
      attempts to become proficient readers while also possibly increasing the
      frequency of their problem behaviors. Dialogic Reading is a scientifically
      validated shared storybook reading intervention that is known to boost at risk
      children's oral vocabulary skills. As such, use of Dialogic Reading is one
      potential way to help children avoid both later reading failure and the negative
      outcomes associated with poor behavior. In this article, we detail both (a) a
      research-based rationale for using Dialogic Reading and (b) Dialogic Reading's
      set of procedures and prompts.

PMID- 25960621
TI  - Markers of inflammation associated with plaque progression and instability in
      patients with carotid atherosclerosis.
AB  - Atherosclerosis is the focal expression of a systemic disease affecting medium-
      and large-sized arteries, in which traditional cardiovascular risk factor and
      immune factors play a key role. It is well accepted that circulating biomarkers,
      including C-reactive protein and interleukin-6, reliably predict major
      cardiovascular events, including myocardial infarction or death. However, the
      relevance of biomarkers of systemic inflammation to atherosclerosis progression
      in the carotid artery is less established. The large majority of clinical studies
      focused on the association between biomarkers and subclinical atherosclerosis,
      that is, carotid intima-media thickening (cIMT), which represents an earlier
      stage of the disease. The aim of this work is to review inflammatory biomarkers
      that were associated with a higher atherosclerotic burden, a faster disease
      progression, and features of plaque instability, such as inflammation or
      neovascularization, in patients with carotid atherosclerotic plaque, which
      represents an advanced stage of disease compared with cIMT. The association of
      biomarkers with the occurrence of cerebrovascular events, secondary to carotid
      plaque rupture, will also be presented. Currently, the degree of carotid artery
      stenosis is used to predict the risk of future cerebrovascular events in patients
      affected by carotid atherosclerosis. However, this strategy appears suboptimal.
      The identification of suitable biomarkers could provide a useful adjunctive
      criterion to ensure better risk stratification and optimize management. 

PMID- 25960624
TI  - Learning Time-Varying Coverage Functions.
AB  - Coverage functions are an important class of discrete functions that capture the
      law of diminishing returns arising naturally from applications in social network
      analysis, machine learning, and algorithmic game theory. In this paper, we
      propose a new problem of learning time-varying coverage functions, and develop a
      novel parametrization of these functions using random features. Based on the
      connection between time-varying coverage functions and counting processes, we
      also propose an efficient parameter learning algorithm based on likelihood
      maximization, and provide a sample complexity analysis. We applied our algorithm
      to the influence function estimation problem in information diffusion in social
      networks, and show that with few assumptions about the diffusion processes, our
      algorithm is able to estimate influence significantly more accurately than
      existing approaches on both synthetic and real world data.

PMID- 25960625
TI  - Motivation Among Ex-Offenders Exiting Treatment: The Role of Abstinence Self
      Efficacy.
AB  - The relationships between motivation, treatment readiness, and abstinence self
      efficacy were examined among a sample of ex-offenders exiting inpatient treatment
      for substance use disorders. Hierarchical linear regression was conducted to
      examine changes in participants' motivation levels in relation to abstinence self
      efficacy beyond what would be expected from treatment readiness and substance
      use. Abstinence self-efficacy predicted significant decreases in motivation
      whereas treatment readiness and substance use predicted significant increases.
      However, there was not a significant relationship between abstinence self
      efficacy and treatment readiness. Findings suggest that motivation for change
      among persons with substance use disorders is related to their self-efficacy for
      ongoing abstinence.

PMID- 25960626
TI  - An Incidental Abscess in a Patient with Acquired Immunodeficiency Syndrome.

PMID- 25960627
TI  - Multilevel Functional Principal Component Analysis for High-Dimensional Data.
AB  - We propose fast and scalable statistical methods for the analysis of hundreds or
      thousands of high dimensional vectors observed at multiple visits. The proposed
      inferential methods do not require loading the entire data set at once in the
      computer memory and instead use only sequential access to data. This allows
      deployment of our methodology on low-resource computers where computations can be
      done in minutes on extremely large data sets. Our methods are motivated by and
      applied to a study where hundreds of subjects were scanned using Magnetic
      Resonance Imaging (MRI) at two visits roughly five years apart. The original data
      possesses over ten billion measurements. The approach can be applied to any type
      of study where data can be unfolded into a long vector including densely observed
      functions and images. Supplemental materials are provided with source code for
      simulations, some technical details and proofs, and additional imaging results of
      the brain study.

PMID- 25960628
TI  - Young People's Views on Electronic Mental Health Assessment: Prefer to Type than
      Talk?
AB  - For mental health professionals to provide personalized early interventions,
      young people need to disclose sensitive information to a clinician they are
      unlikely to have yet formed a relationship with. We conducted in-depth
      qualitative interviews with 129 young people aged 12-25 years from several sites
      across Australia to gauge views on whether young people thought that an
      electronic psychosocial assessment tool could help them initially disclose
      personal information. Additionally, we were interested in whether young people
      from different demographic groups held similar views around using the e-tool.
      Results provided support for the use of an e-tool, with most young people stating
      that it could help in the disclosure of particularly embarrassing problems. The
      main advantages reported were that the e-tool would support disclosure without
      fear of judgment by health professionals, and would enable young people greater
      input in deciding what to focus on. Young people who held a preference to simply
      talk were most concerned about the clinician missing non-verbal cues. These
      findings highlight the value of incorporating electronic options within clinical
      practice, but also the need for health professionals to work within a flexible
      framework guided by the individual preferences of each of their clients.

PMID- 25960629
TI  - Examining Change in Therapeutic Alliance to Predict Youth Mental Health Outcomes.
AB  - OBJECTIVE: To examine the link between therapeutic alliance and youth outcomes.
      METHOD: The study was conducted at a group-home with 112 youth with a disruptive
      behavior diagnosis. Therapeutic alliance was collected routinely via youth and
      staff report. Outcome data were collected using youth and staff reports of
      externalizing behavior as well as behavioral incidents occurring during care.
      Outcome data were collected following intake into services and at 6 and 12 months
      of care. Data were analyzed to examine (1) if youth behavior problems at intake
      were predictive of therapeutic alliance and (2) if changes in alliance were
      predictive of subsequent youth outcomes. These were conducted with a 6-month
      service-delivery model and replicated with a 12-month model. RESULTS: There was
      some support for the first hypothesis, that initial levels of youth externalizing
      behavior would be related to alliance ratings; however, most of the effects were
      marginally significant. The second hypothesis, that changes in therapeutic
      alliance would be related to subsequent youth outcomes, was supported for the 6
      month model, but not the 12-month model. CONCLUSIONS: Changes in therapeutic
      alliance may be predictive of youth outcomes during care. Additional research
      into examining therapeutic alliance trajectories is warranted to improve mental
      health services for youth.

PMID- 25960630
TI  - Bringing Culture Into Parent Training With Latinos.
AB  - Traditional frameworks of parenting have failed to capture the distinctive nature
      of parenting in Latino families. Cultural values likely influence parenting
      practices. The study of cultural values may allow us to identify aspects of
      parenting that are unique to Latinos and which complement traditional frameworks
      of parenting. This paper presents qualitative work on two Latino cultural values,
      familismo and respeto, and examines ways in which these values may inform the
      provision of standard parent training programs with Latinos. The first study is
      an ethnography that explored the value of familismo. The second study consisted
      of focus groups in which Latina mothers discussed the value of respeto. Findings
      from these two studies are used to examine the cultural congruence of the
      characteristics of parent training programs and the Latino values of familismo
      and respeto. In light of the issues identified, clinical guidelines for working
      with Latino parents in parent training programs are offered.

PMID- 25960631
TI  - Accountable Care Organizations in the U.S. Health Care System.

PMID- 25960632
TI  - D-cycloserine augmentation in behavioral therapy for obsessive-compulsive
      disorder: a meta-analysis.
AB  - OBJECTIVE: To evaluate the overall effect of D-cycloserine (DCS) augmentation on
      exposure and response prevention (ERP) therapy for obsessive-compulsive disorder
      (OCD). METHODS: Clinical studies on the effect of DCS augmentation on ERP therapy
      for OCD compared to placebo were included for meta analysis. The primary outcome
      was the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Meta-analyses were
      performed with a random-effect model or a fixed-effect model using the Cochrane
      Review Manager (RevMan, version 5.2) to calculate the odds ratio and the mean
      difference, with their corresponding 95% confidence intervals. RESULTS: A total
      of six studies was included in the current meta-analyses, and their data were
      extracted. Among them, four were for analyses of DCS and Y-BOCS at midtreatment,
      six for analysis at posttreatment, and four at 3-month follow-up. Besides, three
      of the six eligible studies were included in the meta-analysis of the DCS and
      Clinical Global Impression-Severity Scale at posttreatment, and three in the meta
      analysis of DCS and proportions of treatment responders and of subjects attaining
      clinical remission status criteria at posttreatment. Our meta-analyses do not
      reveal a significant effect of DCS augmentation in ERP therapy for OCD patients,
      except when measured at midtreatment. Compared to the placebo group, DCS
      augmentation did show a trend toward significantly lower/decreased Y-BOCS; when
      measured at posttreatment and in the subpopulation of DCS taken before some of
      the ERP sessions, DCS augmentation showed a trend toward significantly
      lower/decreased Y-BOCS. CONCLUSION: Our result suggested that with the careful
      optimization of DCS-augmented ERP therapy by fine-tuning timing and dosing of DCS
      administration and number and frequency of ERP sessions, DCS may enhance the
      efficacy of ERP therapy in reducing the symptomatic severity of OCD patients,
      especially at early stage of the treatment; therefore, DCS augmentation could
      possibly reduce treatment cost, reduce treatment drop and refusal rate, and help
      to improve access to the limited number of experienced therapists.

PMID- 25960633
TI  - Preparation, characterization, and in vivo study of rhein-loaded poly(lactic-co
      glycolic acid) nanoparticles for oral delivery.
AB  - A novel rhein formulation based on poly(lactic-co-glycolic acid) (PLGA)
      nanoparticles (NPs) suitable for oral administration was developed in this study.
      The designed nanosystems were obtained by a modified spontaneous emulsification
      solvent diffusion method. The morphology of rhein-loaded PLGA NPs showed a
      spherical shape with a smooth surface, without any particle aggregation. Mean
      size of the NPs was 140.5+/-4.3 nm, and the zeta potential was -16.9+/-3.1 mV.
      The average drug loading was 3.9%+/-0.7%, and encapsulation efficiency was
      84.5%+/-6.2%. Meanwhile, NPs are characterized by the slower release (only about
      70% of rhein is released within 5 hours), and the model that fitted best for
      rhein released from the NPs was Higuchi kinetic model with correlation
      coefficient r=0.9993, revealing that rhein could be controlled released from the
      NPs. In vivo, NPs altered the distribution of rhein, and the half-life after oral
      administration was prolonged remarkably more than those of suspensions (22.6
      hours vs 4.3 hours). The pharmacokinetic results indicated that the NPs had
      sustained-release efficacy. The area under the curve0-infinity of the NPs
      formulation was 3.07-fold higher than that of suspensions, suggesting that the
      encapsulated rhein had almost been absorbed in rats over the period of 12 hours.
      Although rhein-loaded PLGA NP formulations are hopefully used as a
      chemotherapeutic or adjuvant agent for human gastric cancer (SGC-7901), their in
      vivo antitumor effect and mechanisms at the molecular level still need further
      study. 

PMID- 25960634
TI  - Profile of conbercept in the treatment of neovascular age-related macular
      degeneration.
AB  - In developed countries, age-related macular degeneration (AMD) is the leading
      cause of irreversible blindness in individuals over the age of 65 years. Vascular
      endothelial growth factor (VEGF) plays a vital role in the formation of
      neovascular AMD. VEGF regulates angiogenesis, enhances vascular permeability, and
      drives the formation of choroidal neovascularization. As a result of the
      introduction of anti-VEGF drugs, the incidence of blindness from neovascular AMD
      has greatly reduced. Anti-VEGF drugs are used as a first-line treatment for
      neovascular AMD. The most recent anti-VEGF drug is conbercept, also named KH902,
      which was approved for the treatment of neovascular AMD by the China Food and
      Drug Administration in December 2013. In this review, recent clinical information
      regarding the use of conbercept to treat neovascular AMD is summarized.
      Conbercept is a soluble receptor decoy that blocks all isoforms of VEGF-A, VEGF
      B, VEGF-C, and PlGF, which has a high binding affinity to VEGF and a long half
      life in vitreous. Preclinical studies have demonstrated its anti-angiogenesis
      activity in both ocular neovascular disease models and tumor models. Clinical
      trials of conbercept have shown its superior efficacy and safety. Patients
      respond well even with 3-month treatment intervals following loading doses once a
      month for 3 months. The potential therapeutic effect of conbercept on the
      treatment of polypoidal choroidal vasculopathy, a special type of neovascular
      AMD, is also promising. In summary, conbercept is a new treatment option for
      ophthalmologists and their patients and may help address the limitations of
      current anti-VEGF drugs. 

PMID- 25960635
TI  - A novel misoprostol delivery system for induction of labor: clinical utility and
      patient considerations.
AB  - Induction of labor is one of the most commonly performed obstetric procedures and
      will likely become more common as the reproductive population in developed
      nations changes. As the proportion of women undergoing induction grows, there is
      a constant search for more efficacious ways to induce labor while maintaining
      fetal and maternal safety as well as patient satisfaction. With almost half of
      induced labors requiring cervical ripening, methods for achieving active labor
      and vaginal delivery are constantly being investigated. Prostaglandins have been
      shown to be effective induction agents, and specifically vaginal misoprostol,
      used off-label, have been widely utilized to initiate cervical ripening and
      active labor. The challenge is to administer this medication accurately while
      maintaining the ability to discontinue the medication when needed. The
      misoprostol vaginal insert initiates cervical ripening utilizing a delivery
      system that controls medication release and can be rapidly removed. This paper
      reviews the design, development, and clinical utility of the misoprostol vaginal
      insert for induction of labor as well as patient considerations related to the
      delivery system. 

PMID- 25960636
TI  - Modifying tetramethyl-nitrophenyl-imidazoline with amino acids: design,
      synthesis, and 3D-QSAR for improving inflammatory pain therapy.
AB  - With the help of pharmacophore analysis and docking investigation, 15 novel 1
      (4,4,5,5-tetramethyl-2-(3-nitrophenyl)-4,5-dihydroimidazol-1-yl)-oxyacetyl-L
      amino acids (6a-o) were designed, synthesized, and assayed. On tail-flick and
      xylene-induced ear edema models, 10 MUmol/kg 6a-o exhibited excellent oral anti
      inflammation and analgesic activity. The dose-dependent assay of their
      representative 6f indicates that the effective dose should be 3.3 MUmol/kg. The
      correlation of the three-dimensional quantitative structure-activity relationship
      with the docking analysis provides a basis for the rational design of drugs to
      treat inflammatory pain. 

PMID- 25960637
TI  - Efficacy and safety of ramosetron versus ondansetron for postoperative nausea and
      vomiting after general anesthesia: a meta-analysis of randomized clinical trials.
AB  - BACKGROUND: Postoperative nausea and vomiting is a common side effect of general
      anesthesia. In this study, we performed a meta-analysis on the efficacy and
      safety of ramosetron versus ondansetron in the prevention of postoperative nausea
      and vomiting using the most recently published randomized controlled clinical
      studies. METHODS: PubMed and EMBASE were searched for randomized controlled
      clinical trials comparing the efficacy and safety of ramosetron and ondansetron.
      The meta-analysis was performed using Review Manager version 5.3 (Cochrane
      Collaboration, Oxford, UK). Dichotomous outcomes are presented as the relative
      risk (RR) with a 95% confidence interval (CI). RESULTS: A total of 898 patients
      from nine selected studies were treated with antiemetics after surgery, including
      450 patients who received ondansetron 4 mg and 448 patients who received
      ramosetron 0.3 mg. The meta-analysis showed no statistically significant
      difference between the two groups with regard to prevention of postoperative
      nausea (PON) during different time periods in the 48 hours after surgery. When
      comparing the efficacy of ramosetron and ondansetron in the prevention of
      postoperative vomiting (POV), at various time intervals in the 24 hours after
      surgery, ramosetron was significantly more efficient than ondansetron: 0-6 hours
      (RR 0.46, 95% CI 0.24-0.92; P=0.03), 0-24 hours (RR 0.72, 95% CI 0.52-1.00;
      P=0.05), and 6-24 hours (RR 0.51, 95% CI 0.31-0.84; P=0.008). At other time
      periods between 24 and 48 hours after surgery, ramosetron did not show better
      efficacy than ondansetron. When comparing the safety profiles of ramosetron and
      ondansetron, fewer side effects were recorded in the ramosetron group (RR 0.65,
      95% CI 0.47-0.91; P=0.01). CONCLUSION: Our meta-analysis demonstrates that
      ramosetron was more effective than ondansetron in the prevention of early POV (0
      24 hours) with fewer recorded side effects. However, our study did not reveal any
      statistically significant differences in efficacy between ramosetron and
      ondansetron in the prevention of PON or late POV (at 24-48 hours).

PMID- 25960638
TI  - Critical appraisal of bevacizumab in the treatment of ovarian cancer.
AB  - Bevacizumab is the first molecular-targeted agent to be used for the treatment of
      ovarian cancer. Bevacizumab is a humanized monoclonal antibody targeting vascular
      endothelial growth factor. Two randomized Phase III trials evaluated the
      combination of bevacizumab plus standard cytotoxic chemotherapy for first-line
      treatment of advanced ovarian cancer. Additional Phase III trials evaluated
      bevacizumab combined with cytotoxic chemotherapy in platinum-sensitive and
      platinum-resistant recurrent ovarian cancer. All these trials reported a
      statistically significant improvement in progression-free survival but not in
      overall survival. Furthermore, bevacizumab effectively improved the quality of
      life with regard to abdominal symptoms in recurrent ovarian cancer patients.
      Bevacizumab is associated with adverse events not commonly observed with
      cytotoxic agents used to treat gynecological cancers, such as hypertension,
      bleeding, thromboembolism, proteinuria, delayed wound healing, and
      gastrointestinal events. However, most of these events can be adequately managed
      by gynecologists. The clinical trial results with bevacizumab have supported its
      recent approval in Europe and the United States as a treatment for ovarian
      cancer. This review presents the latest evidence for bevacizumab therapy of
      ovarian cancer and describes selection of patients for personalized treatment. 

PMID- 25960639
TI  - Wnt blockers inhibit the proliferation of lung cancer stem cells.
AB  - BACKGROUND: Previous study has confirmed that the occurrence of Wnt pathway
      activation is associated with risk of non-small-cell lung cancer recurrence.
      However, whether the pharmacologic blocking of the Wnt signaling pathway could
      provide therapeutic possibility remains unknown. The aim of the present study was
      to evaluate the therapeutic functions of the Wnt signaling pathway inhibitor
      pyrvinium pamoate (PP) on lung cancer stem cells (LCSCs) in vitro. METHODS:
      Colony formation and sphere culture were performed to enrich LCSCs from three
      lung cancer cell lines: PC9, SPC-A1, and A549. After confirming stemness by
      immunofluorescence, PP was employed for cell viability assay by comparison with
      three other kinds of Wnt signaling inhibitor: salinomycin, ICG-001, and
      silibinin. The effect of PP on LCSCs was further verified by colony formation
      assay and gene expression analysis. RESULTS: LCSCs were successfully generated by
      sphere culture from SPC-A1 and PC9 cells, but not A549 cells. Immunofluorescence
      assay showed that LCSCs could express pluripotent stem cell markers, including
      NANOG, Oct4, KLF5, and SOX2, and Wnt signaling pathway molecules beta-catenin and
      MYC. Half-maximal inhibitory concentrations of PP on SPC-A1, PC9, and A549 were
      10 nM, 0.44 nM, and 0.21 nM, respectively, which are much lower than those of
      salinomycin, ICG-001, and silibinin. Moreover, significantly decreased colony
      formation and downregulation of pluripotent stem cell signaling pathway were
      observed in lung cancer cells after treatment with PP. CONCLUSION: Wnt signaling
      inhibitor PP can inhibit proliferation of LCSCs, and the Wnt signaling pathway
      could be considered a promising therapeutic or interventional target in lung
      adenocarcinoma.

PMID- 25960640
TI  - Application of a three-microneedle device for the delivery of local anesthetics.
AB  - PURPOSE: We investigated the effectiveness of a newly developed device for the
      delivery of local anesthetics in the treatment of axillary osmidrosis and
      hyperhidrosis. We developed a device with three fine, stainless steel needles
      fabricated with a bevel angle facing outside ("three-microneedle device" [TMD])
      to release a drug broadly and homogeneously into tissue in the horizontal plane.
      Use of this device could reduce the risk of complications when transcutaneous
      injections are undertaken. PATIENTS AND METHODS: Sixteen Japanese patients were
      enrolled. The mean volume of lidocaine hydrochloride per unit area needed to
      elicit anesthesia when using a TMD was compared with that the volume required
      when using a conventional 27-gauge needle. The visual analog scale (VAS) score of
      needlestick pain and injection-associated pain was also compared. RESULTS: The
      mean volume of lidocaine hydrochloride per unit area to elicit anesthesia using
      the TMD was significantly lower than that the volume required when using the
      conventional 27-gauge needle. The VAS score of needlestick pain for the TMD was
      significantly lower than that the VAS score for the 27-gauge needle. CONCLUSION:
      These data suggest that the TMD could be useful for the delivery of local
      anesthetics in terms of clinical efficacy and avoidance of adverse effects.

PMID- 25960641
TI  - The influence of cultural and religious orientations on social support and its
      potential impact on medication adherence.
AB  - PURPOSE: Social support can positively influence patients' health outcomes
      through a number of mechanisms, such as increases in patients' adherence to
      medication. Although there have been studies on the influence of social support
      on medication adherence, these studies were conducted in Western settings, not in
      Asian settings where cultural and religious orientations may be different. The
      objective of this study was to assess the effects of cultural orientation and
      religiosity on social support and its relation to patients' medication adherence.
      METHODS: This was a cross-sectional study of patients with chronic diseases in
      two tertiary hospitals in Selangor, Malaysia. Patients who agreed to participate
      in the study were asked to answer questions in the following areas: 1) perceived
      group and higher authority cultural orientations; 2) religiosity: organizational
      and non-organizational religious activities, and intrinsic religiosity; 3)
      perceived social support; and 4) self-reported medication adherence. Patients'
      medication adherence was modeled using multiple logistic regressions, and only
      variables with a P-value of <0.25 were included in the analysis. RESULTS: A total
      of 300 patients completed the questionnaire, with the exception of 40
      participants who did not complete the cultural orientation question. The mean age
      of the patients was 57.6+/-13.5. Group cultural orientation, organizational
      religious activity, non-organizational religious activity, and intrinsic
      religiosity demonstrated significant associations with patients' perceived social
      support (r=0.181, P=0.003; r=0.230, P<0.001; r=0.135, P=0.019; and r=0.156,
      P=0.007, respectively). In the medication adherence model, only age, duration of
      treatment, organizational religious activity, and disease type (human
      immunodeficiency virus) were found to significantly influence patients' adherence
      to medications (adjusted odds ratio [OR] 1.05, P=0.002; OR 0.99, P=0.025; OR
      1.19, P=0.038; and OR 9.08, P<0.05, respectively). CONCLUSION: When examining
      religious practice and cultural orientation, social support was not found to have
      significant influence on patients' medication adherence. Only age, duration of
      treatment, organizational religious activity, and disease type (human
      immunodeficiency virus) had significant influence on patients' adherence.

PMID- 25960642
TI  - Adherence counseling during patient contacts in swiss community pharmacies.
AB  - PURPOSE: Numerous studies showed the effectiveness of pharmaceutical care in
      improving medication adherence in primary care patients. However, in daily
      pharmacy practice, the provision of pharmaceutical care appears to be limited. We
      aimed at quantifying the content of counseling by community pharmacy staff during
      patient contacts, especially adherence counseling, and at investigating
      pharmacist views about their practice of adherence counseling. PATIENTS AND
      METHODS: A Master's student in Pharmacy observed patient contacts at selected
      community pharmacies in the region of Basel, Switzerland. Content of counseling
      was manually ticked on a checklist with predefined themes (administration, dose,
      effect, and adherence). Pharmacists working in the pharmacy were interviewed on
      triggers, topics, and barriers in adherence counseling. RESULTS: In 20 community
      pharmacies and during a total of 148.1 hours, 1,866 patient contacts were
      observed. During the 1,476 patient contacts including the dispensing of one or
      more medications, counseling was provided to 799 (54.1%) patients; with 735
      (49.8%) patients counseled about administration, 362 (24.5%) about dose, 267
      (18.1%) about effect, and 99 (6.7%) about adherence. Significantly more patients
      received counseling when they obtained prescribed versus over-the-counter
      medication (P=0.002), a new prescription versus a repeat prescription (P<0.001),
      or when they were served by a pharmacist versus by another staff member
      (P<0.001). Of the 33 interviewed pharmacists, all except one reported actively
      approaching patients for adherence counseling. Triggers included medication
      related and patient-related factors. The pharmacists named predominantly product
      centered topics of adherence counseling. The most cited barriers were rejection
      of counseling by the patient and lack of time. CONCLUSION: Half of the patients
      receiving one or more medications were counseled, and only 6.7% of all contacts
      included adherence counseling. Future studies should clarify how barriers to
      adherence counseling at the community pharmacy can be overcome.

PMID- 25960643
TI  - Structural and functional markers of health depending on lifestyle in elderly
      women from Poland.
AB  - OBJECTIVE: To comparatively analyze the rate and magnitude of age-related changes
      between two groups of elderly women with different lifestyles living in Poland:
      women attending a University of the Third Age (active lifestyle) and less-active
      peers not involved in any seniors association. METHODS: The study was conducted
      in 2010-2012. The study design was approved by the Senate Ethics Committee for
      Scientific Research of the University School of Physical Education. In total, 417
      women were recruited. Basic somatic characteristics, body composition, bone
      mineral density, physical fitness, respiratory function, postural stability, and
      body posture were measured. Regression analysis and Student's t-tests for
      independent samples were calculated. RESULTS AND CONCLUSION: The best results
      among the tests assessing functional biological markers of health were found in
      the group of elderly women attending a University of the Third Age. The rate of
      change was larger in the group of seniors leading a less-active lifestyle,
      indicating the important role of a preventive gerontological approach and the
      participation of seniors in programs that accentuate the need for physical
      activity.

PMID- 25960644
TI  - Intramedullary versus extramedullary fixation in the management of
      subtrochanteric femur fractures: a meta-analysis.
AB  - BACKGROUND: Intramedullary and extramedullary fixation methods are used in the
      management of subtrochanteric femur fractures. However, whether intramedullary or
      extramedullary fixation is the primary treatment for subtrochanteric femur
      fractures in adults remains debatable. LEVEL OF EVIDENCE: Meta-analyses of
      prospective studies, level I. MATERIALS AND METHODS: The Cochrane library,
      Embase, Google Scholar, and PubMed databases were searched separately for all
      relevant studies published before January 1, 2015. No language restriction was
      applied. Prospective randomized controlled trials that compared intramedullary or
      extramedullary internal fixation to repair subtrochanteric femur fractures in
      adults were included. We determined intraoperative data, postoperative
      complications, fracture fixation complications, wound infection, hospital stay
      days, and final outcome measures to assess the relative effects of different
      internal fixation methods for the treatment of subtrochanteric femur fractures in
      adults. RESULTS: Six studies were included in our meta-analysis. The relative
      risks (RRs) of revision rate was 83% lower (RR, 0.17, 95% confidence interval
      [CI], 0.05 to 0.60; P=0.006), fixation failure rate was 64% lower (RR, 0.36, 95%
      CI, 0.12 to 1.08; P=0.07), non-union rate was 77% lower (RR, 0.23, 95% CI, 0.07
      to 0.81; P=0.02) in the intramedullary group compared with the extramedullary
      group. No significant differences were found between the intramedullary group and
      extramedullary group for intraoperative data, postoperative complications, wound
      infection, hospital stay days or final outcome measures. CONCLUSION: In
      conclusion, our meta-analysis suggests that there was no significant difference
      in intraoperative data, postoperative complications, wound infection, hospital
      stay days or final outcome measures between intramedullary and extramedullary
      internal fixation. However, a significant decrease occurred in the rate of
      fracture fixation complications for patients treated with intramedullary internal
      fixation, especially in elderly patients. Some differences were not significant,
      but the treatment of elderly subtrochanteric femur fractures using intramedullary
      internal fixation is recommended.

PMID- 25960645
TI  - Helicobacter pylori infection in Chinese patients with atrial fibrillation.
AB  - OBJECTIVE: To explore the relationship between Helicobacter pylori (Hp) infection
      and atrial fibrillation (AF) in Chinese patients. METHODS: A total of 285
      hospitalized patients with AF and 300 patients from Health Screening Center who
      matched age and sex with AF group were enrolled. AF patients were divided into
      two groups: the short-standing AF category (less than a year) and the long
      standing AF category (more than a year). All patients had laboratory testing of
      (13)C urea breath test, high-sensitive C-reactive protein (hs-CRP) and left
      atrial diameter (LAD). We analyzed the difference of these factors in all groups
      and explored the correlation between Hp infection and AF using logistic
      regression analysis. RESULTS: Both AF groups had more hypertension, diabetes, and
      Hp infection than the control group. The Hp value and the hs-CRP level in
      patients with long-standing AF were higher than those in the short-standing AF
      and the control groups (for Hp value: P<0.001 for both and for hs-CRP level:
      P=0.003, 0.002, respectively). The LAD of patients in the long-standing AF group
      was significantly larger than those in the short-standing AF group and control
      group (P=0.001 and P<0.001, respectively). The values of Hp, hs-CRP, and LAD in
      the long-standing AF category were significantly higher than those in the short
      standing AF category (all P<0.05). After controlling the potential confounders,
      Hp value >=40/00, hs-CRP >5 mg/L, and LAD >36 mm were significantly related to
      long-standing AF. CONCLUSION: The values of Hp in patients with long-standing AF
      were significantly higher than those in short-standing AF and control groups. Hp
      delta value >=40/00 is an independent predictor for long-standing AF.

PMID- 25960647
TI  - Is intrathoracic tracheal collapsibility correlated to clinical phenotypes and
      sex in patients with COPD?
AB  - A substantial proportion of patients with chronic obstructive pulmonary disease
      (COPD) develops various degree of intrathoracic tracheal collapsibility. We
      studied whether the magnitude of intrathoracic tracheal collapsibility could be
      different across clinical phenotypes and sex in COPD. Intrathoracic tracheal
      collapsibility measured at paired inspiratory-expiratory low dose computed
      tomography (CT) and its correlation with clinical, functional, and CT
      densitometric data were investigated in 69 patients with COPD according to their
      predominant conductive airway or emphysema phenotypes and according to sex.
      Intrathoracic tracheal collapsibility was higher in patients with predominant
      conductive airway disease (n=28) and in females (n=27). Women with a predominant
      conductive airway phenotype (n=10) showed a significantly greater degree of
      collapsibility than women with predominant emphysema (28.9%+/-4% versus 11.6%+/
      2%; P<0.001). Intrathoracic tracheal collapsibility was directly correlated with
      inspiratory-expiratory volume variation at CT and with forced expiratory volume
      (1 second), and inversely correlated with reduced CT lung density and functional
      residual capacity. Intrathoracic tracheal collapsibility was not correlated with
      cough and wheezing; however, intrathoracic tracheal collapsibility and clinical
      phenotypes of COPD are closely correlated. In patients with a predominant
      emphysematous phenotype, a reduced collapsibility may reflect the mechanical
      properties of the stiff hyperinflated emphysematous lung. The high collapsibility
      in patients with predominant airway disease, mild airway obstruction, and in
      women with this phenotype may reflect chronic airway inflammation. The lack of
      relationship with such symptoms as wheezing, cough, and dyspnea could indicate
      that intrathoracic tracheal collapsibility itself should be considered neither an
      abnormal feature of COPD nor a relevant clinical finding. 

PMID- 25960646
TI  - Role of combined indacaterol and glycopyrronium bromide (QVA149) for the
      treatment of COPD in Japan.
AB  - Once-daily dual-bronchodilator therapy with combined indacaterol and
      glycopyrronium bromide in one device (Ultibro, Breezhaler), often called QVA149,
      was first approved in 2013 in Japan and Europe. As of November 2014, more than 40
      countries had approved this medication except for the USA. This is the first dual
      bronchodilator in one device. Now, the Breezhaler is the only device that can
      provide long-acting muscarinic antagonist (glycopyrronium bromide), long-acting
      beta agonist (indacaterol), and a combination of the two medications (QVA149).
      The choice among the three medications allows a patient to use the same
      inhalation device even when the regimen is changed from single-bronchodilator
      therapy to dual-bronchodilator therapy. In addition, the quick bronchodilation
      effect and once-daily administration can improve patient adherence to medical
      treatment for chronic obstructive pulmonary disease (COPD). To our knowledge, as
      of November 2014, the safety and the efficacy of QVA149 have been evaluated in 14
      randomized controlled trials. The 14 trials generally showed good safety
      profiles, and there were better or not-inferior bronchodilator effects of QVA149
      when compared with placebo, or other inhaled medication. According to the
      Japanese Respiratory Society guidelines, QVA149 is a combination of the two first
      line bronchodilators. Our meta-analysis indicated that QVA149 is superior to the
      salmeterol-fluticasone combination to treat COPD in respect of the frequency of
      adverse effects, exacerbation, pneumonia, and improvement of trough forced
      expiratory volume in 1 second (FEV1). Thus, we believe that QVA149 can be a key
      medication for COPD treatments. 

PMID- 25960648
TI  - Nitric oxide-releasing poly(lactic-co-glycolic acid)-polyethylenimine
      nanoparticles for prolonged nitric oxide release, antibacterial efficacy, and in
      vivo wound healing activity.
AB  - Nitric oxide (NO)-releasing nanoparticles (NPs) have emerged as a wound healing
      enhancer and a novel antibacterial agent that can circumvent antibiotic
      resistance. However, the NO release from NPs over extended periods of time is
      still inadequate for clinical application. In this study, we developed NO
      releasing poly(lactic-co-glycolic acid)-polyethylenimine (PEI) NPs (NO/PPNPs)
      composed of poly(lactic-co-glycolic acid) and PEI/diazeniumdiolate (PEI/NONOate)
      for prolonged NO release, antibacterial efficacy, and wound healing activity.
      Successful preparation of PEI/NONOate was confirmed by proton nuclear magnetic
      resonance, Fourier transform infrared spectroscopy, and ultraviolet/visible
      spectrophotometry. NO/PPNPs were characterized by particle size, surface charge,
      and NO loading. The NO/PPNPs showed a prolonged NO release profile over 6 days
      without any burst release. The NO/PPNPs exhibited potent bactericidal efficacy
      against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas
      aeruginosa concentration-dependently and showed the ability to bind on the
      surface of the bacteria. We also found that the NO released from the NO/PPNPs
      mediates bactericidal efficacy and is not toxic to healthy fibroblast cells.
      Furthermore, NO/PPNPs accelerated wound healing and epithelialization in a mouse
      model of a MRSA-infected wound. Therefore, our results suggest that the NO/PPNPs
      presented in this study could be a suitable approach for treating wounds and
      various skin infections. 

PMID- 25960649
TI  - Delivery of vincristine sulfate-conjugated gold nanoparticles using liposomes: a
      light-responsive nanocarrier with enhanced antitumor efficiency.
AB  - Rapid drug release at the specific site of action is still a challenge for
      antitumor therapy. Development of stimuli-responsive hybrid nanocarriers provides
      a promising strategy to enhance therapeutic effects by combining the unique
      features of each component. The present study explored the use of drug-gold
      nanoparticle conjugates incorporated into liposomes to enhance antitumor
      efficiency. A model drug, vincristine sulfate, was physically conjugated with
      gold nanoparticles and verified by UV-visible and fourier transform infrared
      spectroscopy, and differential scanning calorimetry. The conjugates were
      incorporated into liposomes by film dispersion to yield nanoparticles (113.4 nm)
      with light-responsive release properties, as shown by in vitro release studies.
      Intracellular uptake and distribution was studied in HeLa cells using
      transmission electron microscopy and confocal laser scanning microscopy. This
      demonstrated liposome internalization and localization in endosomal-lysosomal
      vesicles. Fluorescence intensity increased in cells exposed to UV light,
      indicating that this stimulated intracellular drug release; this finding was
      confirmed by quantitative analyses using flow cytometry. Antitumor efficacy was
      evaluated in HeLa cells, both in culture and in implants in vivo in nude mice.
      HeLa cell viability assays showed that light exposure enhanced liposome
      cytotoxicity and induction of apoptosis. Furthermore, treatment with the prepared
      liposomes coupled with UV light exposure produced greater antitumor effects in
      nude mice and reduced side effects, as compared with free vincristine sulfate. 

PMID- 25960650
TI  - Magnetic particle imaging: current developments and future directions.
AB  - Magnetic particle imaging (MPI) is a novel imaging method that was first proposed
      by Gleich and Weizenecker in 2005. Applying static and dynamic magnetic fields,
      MPI exploits the unique characteristics of superparamagnetic iron oxide
      nanoparticles (SPIONs). The SPIONs' response allows a three-dimensional
      visualization of their distribution in space with a superb contrast, a very high
      temporal and good spatial resolution. Essentially, it is the SPIONs'
      superparamagnetic characteristics, the fact that they are magnetically saturable,
      and the harmonic composition of the SPIONs' response that make MPI possible at
      all. As SPIONs are the essential element of MPI, the development of customized
      nanoparticles is pursued with the greatest effort by many groups. Their objective
      is the creation of a SPION or a conglomerate of particles that will feature a
      much higher MPI performance than nanoparticles currently available commercially.
      A particle's MPI performance and suitability is characterized by parameters such
      as the strength of its MPI signal, its biocompatibility, or its pharmacokinetics.
      Some of the most important adjuster bolts to tune them are the particles' iron
      core and hydrodynamic diameter, their anisotropy, the composition of the
      particles' suspension, and their coating. As a three-dimensional, real-time
      imaging modality that is free of ionizing radiation, MPI appears ideally suited
      for applications such as vascular imaging and interventions as well as cellular
      and targeted imaging. A number of different theories and technical approaches on
      the way to the actual implementation of the basic concept of MPI have been seen
      in the last few years. Research groups around the world are working on different
      scanner geometries, from closed bore systems to single-sided scanners, and use
      reconstruction methods that are either based on actual calibration measurements
      or on theoretical models. This review aims at giving an overview of current
      developments and future directions in MPI about a decade after its first
      appearance. 

PMID- 25960651
TI  - Functional consequences for primary human alveolar macrophages following
      treatment with long, but not short, multiwalled carbon nanotubes.
AB  - PURPOSE: Multiwalled carbon nanotubes (MWCNTs) are a potential human health
      hazard, primarily via inhalation. In the lung, alveolar macrophages (AMs) provide
      the first line of immune cellular defense against inhaled materials. We
      hypothesized that, 1 and 5 days after treating AMs with short (0.6 MUm in length;
      MWCNT-0.6 MUm) and long (20 MUm in length; MWCNT-20 MUm) MWCNTs for 24 hours, AMs
      would exhibit increased markers of adverse bioreactivity (cytokine release and
      reactive oxygen species generation) while also having a modified functional
      ability (phagocytosis and migration). METHODS: Primary human AMs were treated
      with short and long MWCNTs for 24 hours, 1 and 5 days after which toxicity end
      points, including cell death, reactive oxygen species generation, and
      inflammatory mediator release, were measured. AM functional end points involving
      phagocytic ability and migratory capacity were also measured. RESULTS: AM
      viability was significantly decreased at 1 and 5 days after treatment with MWCNT
      20 MUm, while superoxide levels and inflammatory mediator release were
      significantly increased. At the same time, there was reduced phagocytosis and
      migratory capacity alongside increased expression of MARCO; this coincided with
      frustrated phagocytosis observed by scanning electron microscopy. In contrast,
      the adverse bioreactivity of the shorter MWCNT-0.6 MUm with AMs (and any
      resulting reduction in AM functional ability) was substantially less marked or
      absent altogether. CONCLUSION: This study shows that after 24-hour treatment with
      long, but not short, MWCNTs, AM function is severely affected up to 5 days after
      the initial exposure. This has potentially significant pathophysiological
      consequences for individuals who may be intentionally (via therapeutic
      applications) or unintentionally exposed to these nanomaterials.

PMID- 25960652
TI  - Insight into molecular dynamics simulation of BRAF(V600E) and potent novel
      inhibitors for malignant melanoma.
AB  - BRAF inhibitors have changed the standard therapeutic protocol for advanced or
      metastatic melanoma which harbored notorious BRAF(V600E) single mutation.
      However, drug resistance to BRAF inhibitors happens just like other cancer
      treatment. In this study, we constructed the ideal BRAF(V600E)-modeled structure
      through homology modeling and introduced the method of structure-based docking or
      virtual screening from the large compound database. Through certain methods of
      molecular dynamics simulation, we realized that BRAF(V600E) had quite prominent
      difference of molecular character or structural variation from the wild-type BRAF
      protein. It might confer the metamorphic character of advanced melanoma for the
      patients who harbored BRAF(V600E) mutation. By the methods of ligand-based
      quantitative structure-activity relationship and molecular dynamics simulation,
      we further recommend that aknadicine and 16beta-hydroxy-19s-vindolinine N-oxide
      from the traditional Chinese medicine are potent novel inhibitors for the
      management of malignant melanoma in the future. 

PMID- 25960654
TI  - Posterior reversible encephalopathy syndrome in a woman with focal segmental
      glomerulosclerosis.
AB  - Posterior reversible encephalopathy syndrome (PRES) is a rare syndrome
      characterized by reversible vasogenic edema in the posterior hemispheres. PRES is
      most often attributed to primary hypertension, pre-eclampsia, and neurotoxicity
      secondary to immunosuppressants such as cyclosporine. Renal disease is an
      infrequent cause of PRES with a majority of cases occurring in adults with
      complete renal failure or in pediatric cases with underlying renal parenchymal
      disease and concurrent immunosuppressive therapy. Typical symptoms include
      seizure, headache, altered mental status, and visual disturbances. PRES is rarely
      associated with cerebral hemorrhage, and even less so with subarachnoid bleeds.
      Herein we report on a 25-year-old female with focal segmental glomerulosclerosis
      who developed PRES. The patient's presentation was more severe as she presented
      with seizure, nephrotic syndrome, and subarachnoid hemorrhage. Computed
      tomography and magnetic resonance imaging with concurrent symptoms led us to the
      final diagnosis. The patient was treated with antihypertensives, diuretics, and
      corticosteroids and follow-up imaging revealed resolution of PRES. Our case
      illustrates that underlying kidney disease even without immunosuppressive agents
      should be added to the list of possible causes for PRES. Symptoms are reversible
      with treatment of underlying cause or offending agent. 

PMID- 25960653
TI  - Reversal of multidrug resistance in MCF-7/Adr cells by codelivery of doxorubicin
      and BCL2 siRNA using a folic acid-conjugated polyethylenimine hydroxypropyl-beta
      cyclodextrin nanocarrier.
AB  - Systemic administration of chemotherapy for cancer often faces drug resistance,
      limiting its applications in cancer therapy. In this study, we developed a simple
      multifunctional nanocarrier based on polyethylenimine (PEI) to codeliver
      doxorubicin (DOX) and BCL2 small interfering RNA (siRNA) for overcoming multidrug
      resistance (MDR) and enhancing apoptosis in MCF-7/Adr cancer cells by combining
      chemotherapy and RNA interference (RNAi) therapy. The low-molecular-weight branch
      PEI was used to conjugate hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and folic
      acid (FA), forming the codelivery nanocarrier (FA-HP-beta-CD-PEI) to encapsulate
      DOX with the cavity HP-beta-CD and bind siRNA with the positive charge of PEI for
      tumor-targeting codelivering drugs. The drug-loaded nanocomplexes (FA-HP-beta-CD
      PEI/DOX/siRNA) showed uniform size distribution, high cellular uptake, and
      significant gene suppression of BCL2, displaying the potential of overcoming MDR
      for enhancing the effect of anticancer drugs. Furthermore, the nanocomplexes
      achieved significant cell apoptosis through a mechanism of downregulating the
      antiapoptotic protein BCL2, resulted in improving therapeutic efficacy of the
      coadministered DOX by tumor targeting and RNA interference. Our study indicated
      that combined RNAi therapy and chemotherapy using our functional codelivery
      nanocarrier could overcome MDR and enhance apoptosis in MDR cancer cells for a
      potential application in treating MDR cancers. 

PMID- 25960655
TI  - Dietary patterns and schizophrenia: a comparison with healthy controls.
AB  - BACKGROUND: It has been reported that the onset of schizophrenia and the physical
      complications after its onset are related to diet. Diet has been considered as a
      variable factor of the pathogenesis of schizophrenia. However, the results of
      studies on this relationship have been inconsistent. Nutrients are consumed as a
      mixture in the diet. It is difficult to study them in isolation because they may
      have mutually complementary effects. The aim of this study was to assess the
      association between dietary patterns and schizophrenia in Japan. METHODS: The
      subjects comprised 237 outpatients aged 30-60 years (123 males and 114 females)
      with diagnoses of either schizophrenia or schizoaffective disorder. The patient
      diagnoses were determined based on medical records. Patients were recruited
      between June 2011 and August 2011. As a reference group, 404 healthy volunteers
      aged 30-60 years (158 males and 246 females) were also included. Demographic data
      (age, sex, and level of education) were collected by face-to-face method
      interviews and self-administered questionnaires. We assessed eating habits over
      the last month using a validated brief self-administered diet history
      questionnaire. We detected dietary patterns through a principal component
      analysis of calorie-adjusted intake; two principal components were retained. The
      principal components for each dietary pattern and for each individual were
      divided into tertiles by principal component scores. RESULTS: We derived two
      dietary patterns by principal component analysis; namely, the "vegetable" dietary
      pattern and the "cereal" dietary pattern. In the "cereal" dietary pattern, the
      high tertile was associated with a significantly increased risk of schizophrenia
      (P<0.001). CONCLUSION: The "cereal" dietary pattern is associated with
      schizophrenia. This article is the first to describe a study examining the
      association of dietary pattern and schizophrenia.

PMID- 25960657
TI  - A novel missense KIT mutation causing piebaldism in one Chinese family associated
      with cafe-au-lait macules and intertriginous freckling.
AB  - Piebaldism is a rare autosomal dominant genodermatosis, manifesting as congenital
      and stable depigmentation of the skin and white forelock. It has been found to be
      associated with mutations in the KIT or SLUG genes. We report a Chinese
      piebaldism family including a 28-year-old woman and her 3-year-old son with
      characteristics of white patches and forelock associated with numerous brown
      macules and patches. Genomic DNA samples of the proband and her son were
      extracted from their peripheral blood. One hundred unrelated healthy individuals
      were used as controls. All coding regions of KIT, SLUG, and NF1 genes were
      amplified by polymerase chain reaction using exon flanking intronic primers and
      Sanger sequencings were performed. DNA sequencing revealed heterozygous missense
      c.2431T>G mutation in exon 17 of the KIT gene in the proband and the affected
      son. No potentially pathogenic variant was identified in SLUG or NF1 genes. The
      nucleotide substitution was not found in 100 unrelated control individuals. This
      study reveals a novel KIT mutation in piebaldism, and it further supports that
      cafe-au-lait macules and intertriginous freckling of piebaldism are parts of
      pigmented anomaly in piebaldism, which does not necessarily represent coexistence
      of neurofibromatosis type 1 (NF1). 

PMID- 25960656
TI  - Association between anxiety and hypertension: a systematic review and meta
      analysis of epidemiological studies.
AB  - BACKGROUND: Epidemiological studies have repeatedly investigated the association
      between anxiety and hypertension. However, the results have been inconsistent.
      This study aimed to summarize the current evidence from cross-sectional and
      prospective studies that evaluated this association. METHODS: Seven common
      databases were searched for articles published up to November 2014. Cross
      sectional and prospective studies that reported an association between the two
      conditions in adults were included. Data on prevalence, incidence, unadjusted or
      adjusted odds ratios or hazard ratios, and 95% confidence intervals (CIs) were
      extracted or calculated by the authors. The pooled odds ratio was calculated
      separately for cross-sectional and prospective studies using random-effects
      models. The Q test and I2 statistic was used to assess heterogeneity. A funnel
      plot and modified Egger linear regression test were used to estimate publication
      bias. RESULTS: The search yielded 13 cross-sectional studies (n=151,389), and the
      final pooled odds ratio was 1.18 (95% CI 1.02-1.37; P Q<0.001; I (2)=84.9%).
      Eight prospective studies with a total sample size of 80,146 and 2,394
      hypertension case subjects, and the pooled adjusted hazard ratio was 1.55 (95% CI
      1.24-1.94; P Q<0.001; I (2)=84.6%). The meta-regression showed that location,
      diagnostic criteria for anxiety, age, sex, sample size, year of publication,
      quality, and years of follow-up (for prospective study) were not sources of
      heterogeneity. CONCLUSION: Our results suggest that there is an association
      between anxiety and increased risk of hypertension. These results support early
      detection and management of anxiety in hypertensive patients.

PMID- 25960658
TI  - Evaluation of the appropriate use of commonly prescribed fluoroquinolones and the
      risk of dysglycemia.
AB  - BACKGROUND: Fluoroquinolones are among the most widely prescribed antibiotics.
      However, concerns about increasing resistant microorganisms and the risk of
      dysglycemia associated with the use of these agents have emerged. OBJECTIVE: The
      primary objective of the study was to evaluate the appropriate use of commonly
      prescribed fluoroquinolones, including appropriate indication, dose, dose
      adjustment in renal impairment, and duration of treatment. The secondary
      objective was to investigate the dysglycemic effect of fluoroquinolone use
      (hypoglycemia and/or hyperglycemia) in diabetic and nondiabetic patients.
      METHODS: A prospective observational study at a teaching hospital in Lebanon was
      conducted over a 6-month period. A total of 118 patients receiving broad-spectrum
      fluoroquinolones (levofloxacin, ciprofloxacin, and moxifloxacin) were identified.
      Patients were mainly recruited from internal medicine floors and intensive care
      units. RESULTS: The final percentage for the appropriate indication, dose, and
      duration of fluoroquinolone therapy was 93.2%, 74.6%, and 57.6%, respectively. A
      total of 57.1% of the patients did not receive the appropriate dose adjustment
      according to their level of renal impairment. In addition, dysglycemia occurred
      in both diabetic and nondiabetic patients. Dysglycemia was more frequently
      encountered with ciprofloxacin (50.0%), followed by levofloxacin (42.4%) and
      moxifloxacin (7.6%). Hyperglycemia was more common than hypoglycemia in all
      groups. The highest incidence of hyperglycemia occurred with levofloxacin
      (70.0%), followed by ciprofloxacin (39.0%) and moxifloxacin (33.3%). In contrast,
      hypoglycemia did not occur in the ciprofloxacin group, but it was more common
      with moxifloxacin (11.1%) and levofloxacin (6.0%). CONCLUSION: The major clinical
      interventions for the future will adjust the dose and duration of therapy with
      commonly prescribed fluoroquinolones. The incidence of hypoglycemia was less
      common than hyperglycemia.

PMID- 25960659
TI  - Reducing health disparities in underserved communities via interprofessional
      collaboration across health care professions.
AB  - Health disparities can negatively impact subsets of the population who have
      systematically experienced greater socioeconomic obstacles to health. Health
      disparities are pervasive across the United States and no single health care
      profession can tackle this national crisis alone. It is essential that all health
      care providers work collaboratively toward the overarching goal of systematically
      closing the health disparities gap. Interprofessional collaboration is the
      foundation needed for health care providers to support patient needs and reduce
      health disparities in public health. Let us reach across the silos we work within
      and collaborate with our colleagues. Stand up and begin thinking about our
      communities, our patients, and the future overall health status of the population
      for the United States. 

PMID- 25960660
TI  - HES1 is an independent prognostic factor for acute myeloid leukemia.
AB  - HES1 is the target of Notch signaling which is reported to affect cell
      differentiation and maintain the cells in G0 phase in various tissues including
      the hematopoietic tissue. HES1 expression appears to be an independent prognostic
      factor for survival in a heterogeneous group of acute myeloid leukemia (AML)
      patients. To better assess its significance, we analyzed HES1 expression in a
      group of non-core binding factor AML patients and correlated its expression with
      the overall survival and relapse-free survival of AML patients. First, we
      detected the messenger RNA expression of HES1 in 40 patients with AML by real
      time polymerase chain reaction. The top 50% of AML cases with the high HES1
      expression were compared with the rest of the AML cohort. Overall survival was
      calculated from the date of diagnosis until the date of death from any cause or
      until the date of final follow-up. Relapse-free survival was determined for
      responders from the time of diagnosis until relapse or death from any cause. We
      showed that the lower-expression group had a shorter overall survival time and
      shorter relapse-free survival time compared with those of the high-expression
      group (37.6+/-1.6 versus 54.0+/-1.3 months, 28.6+/-1.8 months versus 44.8+/-2.1
      months, respectively, P<0.05), and Cox regression showed that HES1 was an
      independent prognostic factor. In all, we conclude that expression of HES1 is a
      useful prognostic factor for patients with non-core binding factor AML. 

PMID- 25960661
TI  - Comparison of uncommon EGFR exon 21 L858R compound mutations with single
      mutation.
AB  - Non-small-cell lung cancer with epidermal growth factor receptor (EGFR) mutation
      is sensitive to EGFR tyrosine kinase inhibitors (TKIs). But little is known about
      the response to EGFR TKIs and the prognostic role of compound mutations. This
      study compared the uncommon EGFR exon 21 L858R compound mutations with single
      mutation to characterize EGFR compound mutations and investigated their response
      to EGFR TKI treatment. We retrospectively screened 799 non-small-cell lung cancer
      patients from August 1, 2009 to June 1, 2012 by EGFR mutation testing. EGFR
      mutations were detected in 443 patients, with 22 (4.97%) compound mutations.
      Subsequently, six patients with EGFR exon 21 L858R compound mutations and 18
      paired patients with single L858R mutation were well characterized. Finally, we
      also analyzed the EGFR TKI treatment response and patients' outcomes of compound
      or single L858R mutations. There was no differential treatment effect on the
      disease control rate and objective response rate between the L858R compound
      mutations and single mutation groups. No significant difference in overall
      survival or progression-free survival of these two groups was found by log-rank
      test. In conclusion, we demonstrated that no significant difference was detected
      in the response to EGFR TKIs and patients' outcomes in the compound and single
      mutation groups. 

PMID- 25960662
TI  - Pilot study investigating the prognostic significance of thymidine phosphorylase
      expression in patients with metastatic breast cancer: a single institution
      retrospective analysis.
AB  - BACKGROUND: The thymidine phosphorylase (TP) enzyme is expressed in higher levels
      in cancer tissue when compared with normal tissue. It is involved in the
      intratumoral activation of widely prescribed pyrimidine-derived antimetabolites
      such as 5'-deoxy-5-fluorouridine and capecitabine (Xeloda((r))). The purpose of
      this study was to determine the clinical correlation between TP expression in
      tumor tissue and the clinical outcome of capecitabine-based therapy in patients
      with locally advanced (stage III) or metastatic breast cancer (stage IV).
      METHODS: The following variables were analyzed as potential determinants of
      benefit from a capecitabine-based therapy: TP expression, estrogen receptor (ER)
      and progesterone receptor (PR) status, human epidermal growth factor receptor-2
      status, and Ki67 status. This was accomplished by immunohistochemical analysis of
      paraffin-embedded cancer tissues from 18 patients with breast cancer treated with
      at least one cycle of capecitabine. Clinical outcome was measured as time to
      progression. RESULTS: TP staining intensities in both the invasive and in situ
      components in patients with lobular and ductal carcinomas were reported. Higher
      levels of TP in the invasive component were expressed in ER-negative tumors when
      compared with ER-positive tumors (P<0.05). The ER-positive group expressing lower
      levels of TP had a median time to progression of 13 months compared with the ER
      negative group expressing higher levels of TP which had a median time to
      progression of 7.5 months (P=0.14). CONCLUSION: Patients with ER-positive tumors
      expressing lower levels of TP exhibit a longer time to progression when compared
      with patients with ER-negative tumors. Consequently, tumor TP expression does not
      seem to predict the outcome of capecitabine-based chemotherapy.

PMID- 25960663
TI  - Progression-free survival as a surrogate endpoint for overall survival in
      patients with third-line or later-line chemotherapy for advanced gastric cancer.
AB  - BACKGROUND: The correlation between overall survival (OS) and progression-free
      survival (PFS) has been evaluated in patients with metastatic or advanced gastric
      cancer who have received first-line and/or second-line chemotherapy. However, no
      corresponding analysis has been done for patients who have undergone third-line
      or later-line chemotherapy. METHODS: A total of 303 patients from the Phase
      II/III studies of apatinib were pooled (the Phase II study as a training data
      set, the Phase III study as a testing data set). Landmark analyses of PFS at 2
      months from randomization were performed to minimize lead time bias. The Cox
      proportional hazard model was used to test for the significance effect of PFS
      rate at 2 months in predicting OS. Additionally, the PFS/OS correlations were
      evaluated by the normal induced copula (National Institute for Health and Care
      Excellence) estimation model. RESULTS: The median OS was 3.37 months (95%
      confidence interval 2.63-3.80) in patients who experienced progression at 2
      months and 5.67 months in patients who did not (95% confidence interval 4.83
      6.67; P<0.0001). Compared with patients who did not progress at 2 months, the
      adjusted hazard ratio for death was 3.39 (95% confidence interval 1.79-6.41;
      P<0.0001) for patients who experienced progression at 2 months. Moreover, the
      correlation of PFS/OS was 0.84 (95% confidence interval 0.74-0.90). Similar
      results were found in the testing data set. CONCLUSION: These results indicate
      that PFS correlates strongly with OS, suggesting PFS may be a useful early
      endpoint for patients with advanced gastric cancer who have undergone third-line
      or later-line chemotherapy. These observations require prospective validation.

PMID- 25960664
TI  - Clinical applications of PD-1-based therapy: a focus on pembrolizumab (MK-3475)
      in the management of melanoma and other tumor types.
AB  - Preclinical work has led to an increased understanding of the immunomodulatory
      mechanisms involved in the regulation of the antitumor response in a variety of
      tumor types. PD-1 (programmed death 1) appears to be a key checkpoint involved in
      immune suppression in the tumor microenvironment, even in diseases not previously
      thought to be sensitive to immune manipulation. More recently, the subsequent
      clinical development of PD-1-based therapy has resulted in a major breakthrough
      in the field of oncology. Pembrolizumab, a humanized highly selective IgG4 anti
      PD-1 monoclonal antibody, was recently approved for the treatment of advanced
      melanoma based on promising early-phase clinical data. Encouraging results have
      also been seen in other malignancies, and PD-1-targeted therapies are likely to
      markedly change the treatment landscape. Future work will center on rationally
      designed combination strategies in order to potentiate the antitumor immune
      response and overcome mechanisms of resistance. 

PMID- 25960665
TI  - Randomized Phase II trial of paclitaxel plus valproic acid vs paclitaxel alone as
      second-line therapy for patients with advanced gastric cancer.
AB  - The standard regimen of second-line chemotherapy for patients with unresectable
      gastric cancer has not been established. However, weekly paclitaxel (wPTX) has
      become the preferable second-line chemotherapy in Japan. Histone deacetylase
      (HDAC) inhibitors have been shown to have antiproliferative activity through cell
      cycle arrest, differentiation, and apoptosis in gastric cancer cells. One HDAC
      inhibitor, valproic acid (VPA), also inhibits tumor growth by inducing apoptosis,
      and enhances the efficacy of paclitaxel in a mouse xenograft model of gastric
      cancer. wPTX plus VPA as a second-line chemotherapy is expected to improve
      survival in gastric cancer patients. A multicenter randomized Phase II study was
      conducted to compare the effects of wPTX plus VPA and wPTX alone. A total of 66
      patients participated in this study. The primary end point of the study was
      overall survival, and secondary end points were progression-free survival,
      response rate, and assessment of peripheral neuropathy. 

PMID- 25960666
TI  - A spectrum of cutaneous toxicities from erlotinib may be a robust clinical marker
      for non-small-cell lung therapy: a case report and literature review.
AB  - Some literature suggests that an EGFR inhibition-induced rash can be used as a
      clinical marker, but few studies report the correlation between a spectrum of
      cutaneous toxicities from EGFR inhibition and drug efficacy. We report about a
      woman with a stage IV lung adenocarcinoma using erlotinib monotherapy, who
      experienced a spectrum of cutaneous toxicities, including papulopustular rash,
      mucositis, pruritus, xerosis, paronychia, and facial hirsutism. With treatment,
      her metastatic lesions shrunk remarkably. This report suggests that some non
      small-cell lung cancer patients experiencing a spectrum of cutaneous toxicities
      might have a good tumor response using erlotinib monotherapy. Our findings may
      provide a method for clinicians to predict erlotinib efficacy in non-small-cell
      lung cancer therapy without knowledge of the EGFR mutation status. 

PMID- 25960667
TI  - Effect of blood type on survival of Chinese patients with esophageal squamous
      cell carcinoma.
AB  - BACKGROUND: The aim of this study was to evaluate the prognostic value of ABO
      blood group in Chinese patients with esophageal squamous cell carcinoma (ESCC)
      after esophagectomy. METHODS: This study was a retrospective review of the
      records of 548 patients with ESCC who received cytoreductive surgery between
      October 2002 and March 2007. The prognostic impact of ABO blood group on overall
      survival (OS) was analyzed. RESULTS: The median follow-up time was 37 months, and
      the 5-year OS was 43.3%. The overall 5-year OS was 41.2%, 49.7%, 44.0%, and 29.8%
      for the A, B, O, and AB groups, respectively (P=0.038). Among patients with
      negative lymph nodes (LNs), the 5-year OS was 59.0%, 68.2%, 57.9%, and 28.6% for
      the A, B, O, and AB groups, respectively (P<0.001), but blood type had no value
      in predicting the OS of patients with positive LNs (P=0.524). In multivariate Cox
      regression analysis of all patients, ABO blood group was not an independent
      prognostic factor of OS. However, in patients with negative LNs, blood type was
      an independent prognostic factor of OS, and the higher risk of death for patients
      of type AB versus non-AB significant in multivariate analyses (hazard ratio [HR],
      2.576; 95% confidence interval [CI], 1.349-4.919; P=0.004). CONCLUSION: ABO blood
      group is associated with survival in Chinese patients with ESCC. Patients with
      blood type AB had a significantly worse OS than patients with non-AB type,
      especially in patients with negative LNs.

PMID- 25960668
TI  - Severe thrombocytopenia after dasatinib treatment in a patient with Philadelphia
      chromosome-positive chronic myeloid leukemia.
AB  - Dasatinib, a second-generation tyrosine kinase inhibitor, is used for treating
      patients with Philadelphia chromosome (Ph) positive leukemia, especially for
      those who are resistant or intolerant to imatinib. The common adverse effects
      associated to its use include myelosuppression, nausea, diarrhea, and peripheral
      edema. This study reports a very rare case of a 60-year-old male who suffered
      from severe thrombocytopenia after dasatinib administration. The platelet count
      did not increase even after dasatinib had been discontinued for more than 6
      months. Various means had been tried, but the count of platelet did not increase,
      and the result was not optimistic. This is the first report of so severe
      thrombocytopenia after dasatinib treatment, and the pathophysiology underlying
      this reaction remains unknown. We hope that this case will help remind clinicians
      to pay more attention to the side effect of thrombocytopenia caused by dasatinib
      in the future. 

PMID- 25960669
TI  - Evaluation and comparison of two commercially available targeted next-generation
      sequencing platforms to assist oncology decision making.
AB  - BACKGROUND: It is widely acknowledged that there is value in examining cancers
      for genomic aberrations via next-generation sequencing (NGS). How commercially
      available NGS platforms compare with each other, and the clinical utility of the
      reported actionable results, are not well known. During the course of the current
      study, the Foundation One (F1) test generated data on a combination of somatic
      mutations, insertion and deletion polymorphisms, chromosomal abnormalities, and
      deoxyribonucleic acid (DNA) copy number changes at ~250* coverage, while the
      Paradigm Cancer Diagnostic (PCDx) test generated the same type of data at >5,000*
      coverage, plus provided messenger RNA (mRNA) expression levels. We sought to
      compare and evaluate paired formalin-fixed paraffin-embedded tumor tissue using
      these two platforms. METHODS: Samples from patients with advanced solid tumors
      were submitted to both the F1 and PCDx vendors for NGS analysis. Turnaround time
      (TAT) was calculated. Biomarkers were considered clinically actionable if they
      had a published association with treatment response in humans and were assigned
      to the following categories: commercially available drug (CA), clinical trial
      drug (CT), or neither option (hereafter referred to as "None"). RESULTS: The
      demographics of the 21 unique patient tumor samples included ten men and eleven
      women, with a median age of 56 years. Due to insufficient archival tissue from
      the same collection period, in one case, we used samples from different
      collections. PCDx reported first results faster than F1 in 20 cases. When
      received at both vendors on the same day, PCDx reported first results for 14 of
      15 cases, with a median TAT of 9 days earlier than F1 (P<0.0001). Categorization
      of CA compared to CT and none significantly favored PCDx (P=0.012). CONCLUSION:
      In the current analysis, commercially available NGS platforms provided clinically
      relevant actionable targets (CA or CT) in 47%-67% of diverse cancer types. In the
      samples analyzed, PCDx significantly outperformed F1 in TAT, and had
      statistically significant higher clinically relevant actionable targets
      categorized as CA.

PMID- 25960671
TI  - Profile of tedizolid phosphate and its potential in the treatment of acute
      bacterial skin and skin structure infections.
AB  - Tedizolid phosphate is the first once-daily oxazolidinone approved by the United
      States Food and Drug Administration for the treatment of acute bacterial skin and
      skin structure infections (ABSSSI). It is more potent in vitro than linezolid
      against methicillin-resistant Staphylococcus aureus (MRSA) and other gram
      positive pathogens causing ABSSSI, even retaining activity against some linezolid
      resistant strains. Tedizolid is approximately 90% protein bound, leading to lower
      free-drug concentrations than linezolid. The impact of the effect of food, renal
      or hepatic insufficiency, or hemodialysis on tedizolid's pharmacokinetic have
      been evaluated, and no dosage adjustment is needed in these populations. In
      animal and clinical studies, tedizolid's effect on bacterial killing is optimized
      by the free-drug area under the curve to minimum inhibitory concentration ratio
      (fAUC/MIC). The 200 mg once-daily dose is able to achieve the target fAUC/MIC
      ratio in 98% of simulated patients. Two Phase III clinical trials have
      demonstrated the noninferiority of tedizolid 200 mg once daily for 6 days to
      linezolid 600 mg twice daily for 10 days. In vitro, animal, and clinical studies
      have failed to demonstrate that tedizolid inhibits monoamine oxidase to a
      clinically relevant extent. Tedizolid has several key advantages over linezolid
      including once daily dosing, decreased treatment duration, minimal interaction
      with serotonergic agents, possibly associated with less adverse events associated
      with the impairment of mitochondrial protein synthesis (eg, myelosuppression,
      lactic acidosis, and peripheral/optic neuropathies), and retains in vitro
      activity against linezolid-resistant gram-positive bacteria. Economic analyses
      with tedizolid are needed to describe the cost-effectiveness of this agent
      compared with other options used for ABSSSI, particularly treatment options
      active against MRSA. 

PMID- 25960672
TI  - Development of non-alcoholic fatty liver disease scoring system among adult
      medical check-up patients: a large cross-sectional and prospective validation
      study.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common liver
      disease in the community. However, NAFLD remains undiagnosed in most people with
      limited access to imaging facilities in most developing countries. OBJECTIVE: To
      examine the prevalence of NAFLD and to develop the risk scoring model for
      predicting the presence of NAFLD among adult medical check-up patients. METHOD: A
      large prospective cross-sectional study was conducted among medical check-up
      patients who underwent transabdominal ultrasound examination between January and
      December 2013 in Medistra Hospital, Jakarta. Data were obtained from the
      patients' medical records. Logistic regression analyses were undertaken to
      identify the best combination of risk factors for predicting fatty liver using
      the backward (likelihood ratio) approach. The adjusted odds ratio and 95%
      confidence interval were estimated using the logistic regression coefficient. The
      prediction model was assessed using the receiver operating characteristic curve
      and the Hosmer-Lemeshow goodness-of-fit test and was validated on a new,
      prospective cohort. Statistical analysis was done using SPSS version 17. RESULTS:
      A total of 1,054 cases was included in this study. Fatty liver was present in 538
      (51.0%) patients. Bivariate analyses found associations among fatty liver and
      several risk factors. Six risk factors were incorporated to build the final
      prediction model. All scores were summed up to obtain the total score. A
      probability equation was developed by applying linear regression analysis on the
      total score. The prediction model had good diagnostic performance with an area
      under the receiver operating characteristic curve =0.833 (95% confidence interval
      =0.809-0.857). The Hosmer-Lemeshow goodness-of-fit P-value was 0.232, which
      indicated the appropriateness of the logistic regression model to predict fatty
      liver. On the validation set, the scoring system proved to be moderately accurate
      and can potentially be applied to larger population setting. CONCLUSION: The
      presence of fatty liver in NAFLD patients can be predicted using our proposed
      fatty liver scoring system.

PMID- 25960673
TI  - Erratum: Relative nutritional deficiencies associated with centrally acting
      monoamines [Corrigendum].
AB  - [This corrects the article on p. 413 in vol. 5, PMID: 22615537.]. 

PMID- 25960670
TI  - Regulators of pluripotency and their implications in regenerative medicine.
AB  - The ultimate goal of regenerative medicine is to replace damaged tissues with new
      functioning ones. This can potentially be accomplished by stem cell
      transplantation. While stem cell transplantation for blood diseases has been
      increasingly successful, widespread application of stem cell therapy in the
      clinic has shown limited results. Despite successful efforts to refine existing
      methodologies and to develop better ones for reprogramming, clinical application
      of stem cell therapy suffers from issues related to the safety of the
      transplanted cells, as well as the low efficiency of reprogramming technology.
      Better understanding of the underlying mechanism(s) involved in pluripotency
      should accelerate the clinical application of stem cell transplantation for
      regenerative purposes. This review outlines the main decision-making factors
      involved in pluripotency, focusing on the role of microRNAs, epigenetic
      modification, signaling pathways, and toll-like receptors. Of special interest is
      the role of toll-like receptors in pluripotency, where emerging data indicate
      that the innate immune system plays a vital role in reprogramming. Based on these
      data, we propose that nongenetic mechanisms for reprogramming provide a novel and
      perhaps an essential strategy to accelerate application of regenerative medicine
      in the clinic. 

PMID- 25960674
TI  - The effect of nonrecurring alcohol administration on pain perception in humans: a
      systematic review.
AB  - PURPOSE: Alcohol is believed to have pain-dampening effects and is often used as
      self-medication by persons with pain problems; however, experimental evidence
      confirming this effect is scarce. We conducted a systematic review of
      experimental studies on the effects of nonrecurring alcohol administration on
      pain perception in healthy human subjects and the underlying mechanisms. METHOD:
      Three databases (PubMed, PsycINFO, and Web of Science) were searched for relevant
      studies using a predefined algorithm. In a next step, irrelevant articles were
      excluded by screening titles and abstracts. Finally, articles were checked
      regarding a set of methodological criteria; only publications meeting these
      criteria were selected for this review. A total of 14 experimental studies were
      identified. RESULTS: Overall, most of the studies were able to show a pain
      dampening effect of alcohol. However, many of them had methodological
      shortcomings (eg, lack of placebo control, insufficient blinding, or very small
      sample sizes). In addition, comparability is limited due to considerable
      variations in alcohol administration and pain measurement. More importantly,
      potential mechanisms of action and moderating variables have scarcely been
      investigated. CONCLUSION: Despite the frequent use of alcohol as self-medication
      by persons with pain problems, there are to date only a few experimental
      investigations of alcohol effects on pain perceptions. The results of these
      studies suggest that alcohol does in fact have pain-dampening effects. However,
      the mechanisms implicated in these effects are still unknown, and experimental
      research has been limited to pain-free subjects. Future research should provide
      more knowledge about alcohol effects on pain, especially in chronic pain
      patients.

PMID- 25960676
TI  - Erratum: Eribulin for the treatment of metastatic breast cancer: an update on its
      safety and efficacy [Corrigendum].
AB  - [This corrects the article on p. 47 in vol. 7, PMID: 25610001.]. 

PMID- 25960675
TI  - Biopsychosocial predictors of short-term success among people with low back pain
      referred to a physiotherapy spinal triage service.
AB  - BACKGROUND: A spinal triage assessment service may impact a wide range of patient
      outcomes. Investigating potential predictors of success or improvement may reveal
      why some people improve and some do not, as well as help to begin to explain
      potential mechanisms for improvements. The objective of this study was to
      determine which factors were associated with improved short-term self-reported
      pain, function, general health status, and satisfaction in people undergoing a
      spinal triage assessment performed by physiotherapists. METHODS: Participants
      with low back-related complaints were recruited from people referred to a spinal
      triage assessment program (N=115). Participants completed baseline questionnaires
      covering a range of sociodemographic, clinical, and psychological features. Self
      reported measures of pain, function, quality of life, and satisfaction were
      completed at 4 weeks following the assessment. Determination of "success" was
      based on minimal important change scores of select outcome measures. Multivariate
      logistic regression was used to explore potential predictors of success for each
      outcome. RESULTS: Despite the complex and chronic presentation of most
      participants, some reported improvements in outcomes at 4 weeks post assessment
      with the highest proportion of participants demonstrating improvement (according
      to the minimal important change scores) in the Medical Outcomes Survey 36-item
      short-form version 2 physical component summary score (48.6%) and the lowest
      proportion of participants having improvements in the Numeric Pain Rating Scale
      (11.5%). A variety of different sociodemographic, psychological, clinical, and
      other variables were associated with success or improvement in each respective
      outcome. CONCLUSION: There may be a potential mechanism of reassurance that
      occurs during the spinal triage assessment process as those with higher
      psychological distress (measured by the Fear Avoidance Beliefs Questionnaire and
      the Distress and Risk Assessment Measure) were more likely to improve on certain
      outcomes. The use of an evaluation framework guided by a biopsychosocial model
      may help determine potential mechanisms of action for a physiotherapy-delivered
      triage program.

PMID- 25960677
TI  - Smoking cessation in pregnancy: psychosocial interventions and patient-focused
      perspectives.
AB  - BACKGROUND: Smoking during pregnancy causes obstetric and fetal complications,
      and smoking cessation may have great benefits for the mother and the child.
      However, some pregnant women continue smoking even in pregnancy. OBJECTIVE: To
      review the literature addressing the prevalence of smoking during pregnancy,
      explore psychosocial factors associated with smoking, and review the evidence of
      psychosocial interventions for smoking cessation during pregnancy in recent
      years. LITERATURE REVIEW: Computerized Internet search results in PubMed for the
      years spanning from 2004 to 2014, as well as references cited in articles, were
      reviewed. A search for the keywords "smoking cessation pregnancy" and
      "intervention" and "clinical trials" yielded 52 citations. Thirty-five citations
      were identified as useful to this review for the evidence of psychosocial
      interventions for smoking cessation during pregnancy. RESULTS: The prevalence of
      smoking during pregnancy differs by country, reflecting the countries' social,
      cultural, and ethnic backgrounds. Women who had socioeconomic disadvantages,
      problems in their interpersonal relationships, higher stress, depression, less
      social support, and who engaged in health-risk behaviors were more prone to
      smoking during pregnancy. Psychosocial interventions, such as counseling, are
      effective methods for increasing smoking cessation. CONCLUSION: Smokers may have
      various psychosocial problems in addition to health problems. It is important to
      understand each individual's social situation or psychosocial characteristics,
      and a psychosocial intervention focused on the characteristics of the individual
      is required.

PMID- 25960678
TI  - Interventions for postnatal depression assessing the mother-infant relationship
      and child developmental outcomes: a systematic review.
AB  - Postnatal depression (PND) has negative effects on maternal well-being as well as
      implications for the mother-infant relationship, subsequent infant development,
      and family functioning. There is growing evidence demonstrating that PND impacts
      on a mother's ability to interact with sensitivity and responsiveness as a
      caregiver, which may have implications for the infant's development of self
      regulatory skills, making the infant more vulnerable to later psychopathology.
      Given the possible intergenerational transmission of risk to the infant, the
      mother-infant relationship is a focus for treatment and research. However, few
      studies have assessed the effect of treatment on the mother-infant relationship
      and child developmental outcomes. The main aim of this paper was to conduct a
      systematic review and investigate effect sizes of interventions for PND, which
      assess the quality of the mother-infant dyad relationship and/or child outcomes
      in addition to maternal mood. Nineteen studies were selected for review, and
      their methodological quality was evaluated, where possible, effect sizes across
      maternal mood, quality of dyadic relationship, and child developmental outcomes
      were calculated. Finally, clinical implications in the treatment of PND are
      highlighted and recommendations made for further research. 

PMID- 25960679
TI  - An in vitro comparison of tracheostomy tube cuffs.
AB  - INTRODUCTION: The ShileyTM Flexible adult tracheostomy tube with TaperGuardTM
      cuff has been designed through its geometry, materials, diameter, and wall
      thickness to minimize micro-aspiration of fluids past the cuff and to provide an
      effective air seal in the trachea while also minimizing the risk of excessive
      contact pressure on the tracheal mucosa. The cuff also has a deflated profile
      that may allow for easier insertion through the stoma site. This unique design is
      known as the TaperGuardTM cuff. The purpose of the observational, in vitro study
      reported here was to compare the TaperGuardTM taper-shaped cuff to a conventional
      high-volume low-pressure cylindrical-shaped cuff (ShileyTM Disposable Inner
      Cannula Tracheostomy Tube [DCT]) with respect to applied tracheal wall pressure,
      air and fluid sealing efficacy, and insertion force. METHODS: Three sizes of
      tracheostomy tubes with the two cuff types were placed in appropriately sized
      tracheal models and lateral wall pressure was measured via pressure-sensing
      elements on the inner surface. Fluid sealing performance was assessed by
      inflating the cuffs within the tracheal models (25 cmH2O), instilling water above
      the cuff, and measuring fluid leakage past the cuff. To measure air leak, tubes
      were attached to a test lung and ventilator, and leak was calculated by
      subtracting the average exhaled tidal volume from the average delivered tidal
      volume. A tensile test machine was used to measure insertion force for each tube
      with the cuff deflated to simulate clinical insertion through a stoma site.
      RESULTS: The average pressure exerted on the lateral wall of the model trachea
      was lower for the taper-shaped cuff than for the cylindrical cuff under all test
      conditions (P<0.05). The taper-shaped cuff also demonstrated a more even, lower
      pressure distribution along the lateral wall of the model trachea. The average
      air and fluid seal performance with the taper-shaped cuff was significantly
      improved, when compared to the cylindrical-shaped cuff, for each tube size tested
      (P<0.05). The insertion force for the taper-shaped cuff was ~40% less than that
      for the cylindrical-shaped cuff. CONCLUSION: In a model trachea, the ShileyTM
      Flexible Adult tracheostomy tube with TaperGuardTM cuff, when compared to the
      ShileyTM Disposable Inner Cannula Tracheostomy tube with cylindrical cuff,
      exerted a lower average lateral wall pressure and a more evenly distributed
      pressure. In addition, it provided more effective fluid and air seals and
      required less force to insert.

PMID- 25960680
TI  - The relationship between Taekwondo training habits and injury: a survey of a
      collegiate Taekwondo population.
AB  - OBJECTIVE: To correlate training habits of Taekwondo (TKD) athletes to risk for
      injury. BACKGROUND: TKD is a Korean marital art that has been growing in
      popularity, with nearly 2 million individuals practicing the sport in the United
      States. Because of the combative nature of the sport, injuries are an inherent
      risk. However, data on proper training habits, types of injuries sustained during
      training, and recommendations for athletes to avoid injury are lacking.
      Frequently, studies of TKD evaluate athletes' injuries during tournaments, but
      most do not evaluate athletes in training. HYPOTHESIS: Increased training would
      potentially create more injuries secondary to increased exposure. METHODS: This
      is a cross-sectional observational survey of 72 collegiate TKD athletes from the
      Pacific West Sanctioned Taekwondo Tournaments in the 2008-2009 season. Variables
      analyzed during training and competitions were training sessions per week,
      workout habits, belt level, years of experience, and characteristics of injury
      (location, type, mechanism, situation, treatment, and days missed). RESULTS: TKD
      training habits of individuals who practiced four or more times per week (odds
      ratio [OR], 4.5; P=0.005) or sparred for more than 2 hours (OR, 8.7; P=0.003)
      were associated with significantly increased odds (risk) of sustaining an injury.
      Those who had more than 3 years of tournament experience were more likely to
      sustain an injury (OR, 0.198; P=0.020). CONCLUSION: Increased risk for injury
      with more frequent practice and longer sparring should remind coaches and
      trainers that monitoring and adjusting the athletes' training schedules and
      exposure time could decrease the chance of injury. An athlete that has spent more
      years in tournaments along with high-frequency and long-duration training was
      associated with greater risk for injuries. Prevention and education about the
      risk for exposure to injury may may help athletes and trainers promote prevention
      strategies and adjust an athletes' training and tournament schedules to decrease
      the risk for injury.

PMID- 25960681
TI  - Economic evaluation of screening programs for hepatitis C virus infection:
      evidence from literature.
AB  - BACKGROUND: Hepatitis C is a liver infection caused by hepatitis C virus. Its
      main complications are cirrhosis and liver cancer. According to the World Health
      Organization (WHO), more than 185 million people worldwide are infected with
      hepatitis C virus and, of these, 350,000 die every year. Due to the high disease
      prevalence and the existence of effective (and expensive) medical treatments able
      to dramatically change the prognosis, early detection programs can potentially
      prevent the development of serious chronic conditions, improve health, and save
      resources. OBJECTIVE: To summarize the available evidence on the cost
      effectiveness of screening programs for hepatitis C. METHODS: A literature search
      was performed on PubMed and Scopus search engines. Trip database was queried to
      identify reports produced by the major Health Technology Assessment (HTA)
      agencies. Three reviewers dealt with study selection and data extraction blindly.
      RESULTS: Ten papers eventually met the inclusion criteria. In studies focusing on
      asymptomatic cohorts of individuals at general risk the cost/quality adjusted
      life year of screening programs ranged between US $4,200 and $50,000/quality
      adjusted life year gained, while in those focusing on specific risk factors the
      incremental cost-effectiveness ratio ranged between $848 and $128,424/quality
      adjusted life year gained. Age of the target population and disease prevalence
      were the main cost-effectiveness drivers. CONCLUSION: Our results suggest that,
      especially in the long run, screening programs represent a cost-effective
      strategy for the management of hepatitis C.

PMID- 25960682
TI  - Anti-VEGF treatment patterns and associated health care costs in Switzerland:
      findings using real-world claims data.
AB  - BACKGROUND: Little is known about the patterns of actual health care delivery of
      anti-vascular endothelial growth factor (VEGF) treatment in patients with age
      related macular degeneration, diabetic retinopathy, and retinal vein occlusion in
      Switzerland. The purpose of this study was to describe these treatment patterns,
      specifically comparing the numbers of anti-VEGF injections and associated
      expenditures between patients treated with ranibizumab and those treated with
      aflibercept in Switzerland using claims data. METHODS: We identified our study
      patients retrospectively using the Helsana claims database, which includes data
      on approximately 1.2 million subjects with basic health insurance. Patients
      qualified for inclusion if ranibizumab or aflibercept had been initiated between
      December 1, 2012 (when aflibercept was approved by the Federal Office of Public
      Health) and November 30, 2013. Within this set, patients with at least 12 months
      of continuous insurance enrolment in the previous year were considered. In
      univariate analyses, we examined the distribution of demographic data and patient
      characteristics between those receiving ranibizumab and those receiving
      aflibercept. Numbers of injections and associated health care expenditures
      observed during the 6-month follow-up period after incident treatment were the
      two outcomes considered. In multivariate regression analyses, controlling for
      possible confounding factors, we compared differences in these two outcomes
      between patients treated with ranibizumab and those treated with aflibercept.
      RESULTS: Of 3,260 patients who were on anti-VEGF treatment for an
      ophthalmological indication between December 1, 2012 and November 30, 2013, 1,150
      qualified for inclusion. Age, geographic region, and number of physician visits
      in the previous year were significant factors in the number of injections given
      during the 6-month follow-up period. Frequency of injections and associated
      health care expenditures were similar between the groups when correcting for
      differences in patient characteristics. CONCLUSION: Contrary to the
      recommendations regarding frequency of injections and the results of clinical
      studies, aflibercept and ranibizumab are used in a similar fashion in
      Switzerland, resulting in similar total health care expenditures for both these
      anti-VEGF agents.

PMID- 25960683
TI  - Perceived risk factors of health decline: a qualitative study of hospitalized
      patients with multimorbidity.
AB  - BACKGROUND: Effectively preventing and managing chronic illness are key goals for
      health systems worldwide. A growing number of people are living longer with
      multiple chronic illnesses, accompanied by a high degree of treatment burden and
      heavy use of health care resources. People with multimorbidity typically have to
      manage their care needs for a number of years, and from this experience may offer
      valuable perspectives on factors that influenced their health outcome. PURPOSE:
      The purpose of this study was to explore factors that may serve as tipping points
      into poor health from the perspective of hospitalized patients with
      multimorbidity. PARTICIPANTS AND METHODS: Patient interview data were analyzed
      from 43 hospitalized patients with multimorbidities who indicated that something
      could have been done to either avoid or slow down their health decline. The study
      used qualitative description as the analytic method to generate themes from a
      specific question collected through one-on-one interviews. Two reviewers
      independently analyzed and thematically coded the data and reached consensus on
      the final themes after a series of meetings. RESULTS: According to patient
      accounts, factors at the personal level (eg, personal behaviors), provider level
      (eg, late diagnoses), and health care system level (eg, poor care transitions)
      contributed to their health decline. CONCLUSION: This paper focuses on prevention
      in the context of multimorbidity. While some respondents indicated personal
      behaviors that impacted health, many pointed to factors outside themselves
      (providers and the broader health system). The orientation of health care
      systems, historically designed to support acute and episodic care and not
      multimorbidity, places patients, at least in some cases, at additional risk of
      decline. The patient accounts suggest that the notion of prevention should evolve
      throughout the course of illness. A successful health system would embrace this
      notion and see the goal as forestalling not only mortality (as achieved for the
      most part in high socioeconomic nations) but morbidity as well. High rates of
      multimorbidity and health system challenges suggest that we have not yet achieved
      this latter aim.

PMID- 25960684
TI  - Sexual risk behaviors and HIV risk among Americans aged 50 years or older: a
      review.
AB  - Although HIV-related sexual risk behaviors have been studied extensively in
      adolescents and young adults, there is limited information about these behaviors
      among older Americans, which make up a growing segment of the US population and
      an understudied population. This review of the literature dealing with sexual
      behaviors that increase the risk of becoming HIV-infected found a low prevalence
      of condom use among older adults, even when not in a long-term relationship with
      a single partner. A seminal study by Schick et al published in 2010 reported that
      the prevalence of condom use at last intercourse was highest among those aged 50
      59 years (24.3%; 95% confidence interval, 15.6-35.8) and declined with age, with
      a 17.1% prevalence among those aged 60-69 years (17.1%; 95% confidence interval,
      7.3-34.2). Studies have shown that older Americans may underestimate their risk
      of becoming HIV-infected. Substance use also increases the risk for sexual risk
      behaviors, and studies have indicated that the prevalence of substance use among
      older adults has increased in the past decade. As is the case with younger
      adults, the prevalence of HIV infections is elevated among ethnic minorities,
      drug users (eg, injection drug users), and men who have sex with men. When
      infected, older adults are likely to be diagnosed with HIV-related medical
      disorders later in the course of illness compared with their younger
      counterparts. Physicians are less likely to discuss sexual risk behaviors with
      older adults and to test them for HIV compared with younger adults. Thus, it is
      important to educate clinicians about sexual risk behaviors in the older age
      group and to design preventive interventions specifically designed for older
      adults. 

PMID- 25960685
TI  - Implementing meaningful, educative curricula, and assessments in complex school
      environments.
AB  - This commentary uses the lens of curricular implementation to consider issues and
      opportunities afforded by the papers in this special edition. While it is
      interesting to envision innovative approaches to physical education, actually
      implementing changes in the complex institutional school environment is
      exceptionally challenging. These authors have done an excellent job presenting
      viable solutions and fore grounding challenges. Yet, without a concerted effort
      to invite teachers to engage with us in this process, our implementation
      initiatives may not enhance the meaningful and educative process that these
      scholars envision for physical education.

PMID- 25960686
TI  - The influence of stabilizers on the production of gold nanoparticles by direct
      current atmospheric pressure glow microdischarge generated in contact with liquid
      flowing cathode.
AB  - Gold nanoparticles (Au NPs) were prepared by direct current atmospheric pressure
      glow microdischarge (dc-MUAPGD) generated between a miniature argon flow microjet
      and a flowing liquid cathode. The applied discharge system was operated in a
      continuous flow liquid mode. The influence of various stabilizers added to the
      solution of the liquid cathode, i.e., gelatin (GEL), polyvinylpyrrolidone (PVP),
      or polyvinyl alcohol (PVA), as well as the concentration of the Au precursor
      (chloroauric acid, HAuCl4) in the solution on the production growth of Au NPs was
      investigated. Changes in the intensity of the localized surface plasmon resonance
      (LSPR) band in UV/Vis absorption spectra of solutions treated by dc-MUAPGD and
      their color were observed. The position and the intensity of the LSPR band
      indicated that relatively small nanoparticles were formed in solutions containing
      GEL as a capping agent. In these conditions, the maximum of the absorption LSPR
      band was at 531, 534, and 535 nm, respectively, for 50, 100, and 200 mg L-1 of
      Au. Additionally, scanning electron microscopy (SEM) and dynamic light scattering
      (DLS) were used to analyze the structure and the morphology of obtained Au NPs.
      The shape of Au NPs was spherical and uniform. Their mean size was ca. 27, 73,
      and 92 nm, while the polydispersity index was 0.296, 0.348, and 0.456 for Au
      present in the solution of the flowing liquid cathode at a concentration of 50,
      100, and 200 mg L-1, respectively. The production rate of synthesized Au NPs
      depended on the precursor concentration with mean values of 2.9, 3.5, and 5.7 mg
      h-1, respectively.

PMID- 25960688
TI  - Size- and morphology-dependent optical properties of ZnS:Al one-dimensional
      structures.
AB  - Typical morphology substrates can improve the efficiency of surface-enhanced
      Raman scattering; the need for SERS substrates of controlled morphology requires
      an extensive study. In this paper, one-dimensional ZnS:Al nanostructures with the
      width of approximately 300 nm and the length of tens um, and micro-scale
      structures with the width of several um and the length of tens um were
      synthesized via thermal evaporation on Au-coated silicon substrates and were used
      to study their size effects on Raman scattering and photoluminescent spectra. The
      photoluminescence spectra reveal the strongest green emission at a 5 at% Al
      source, which originates from the Al-dopant emission. The Raman spectra reveal
      that the size and morphology of the ZnS:Al nanowires greatly influences the Raman
      scattering, whereas the Al-dopant concentration has a lesser effect on the Raman
      scattering. The observed Raman scattering intensity of the saw-like ZnS:Al
      nanowires with the width of tens nm was eight times larger than that of the bulk
      sample. The enhanced Raman scattering can be regarded as multiple scattering and
      weak exciton-phonon coupling. The branched one-dimensional nanostructure can be
      used as an ideal substrate to enhance Raman scattering.

PMID- 25960687
TI  - Effects of disciplinary cultures of researchers and research trainees on the
      acceptability of nanocarriers for drug delivery in different contexts of use: a
      mixed-methods study.
AB  - The acceptability of nanomedical applications, which have the potential to
      generate ethical and societal impacts, is a significant factor in the deployment
      of nanomedicine. A lack of fit between nanomedical applications and society's
      values may result from a partial consideration of such impacts. New approaches
      for technological evaluation focused on impact perception, acceptance, and
      acceptability are needed to go beyond traditional technology assessment
      approaches used with nanotechnology, which focus mainly on toxicological and
      safety criteria. Using a new evaluative approach based on perceived impacts of
      nanotechnology, the objective of this study was to assess perceptions among
      researchers and research trainees familiar with emergent technologies and from
      different disciplinary background the scope of acceptability judgments made
      towards the use of nanocarriers. This mixed-methods study was based on scenarios
      presenting two types of drug-delivery nanocarriers (carbon, synthetic DNA) in two
      contexts of use (lung cancer treatment, seasonal flu treatment). Researchers and
      research trainees in the natural sciences and engineering, and the social
      sciences and the humanities were invited by email to take part in this project.
      An online questionnaire followed by semi-directed interviews allowed
      characterization of disciplinary divergences regarding to impact perception,
      acceptance, and acceptability of the scenarios. The results suggest that impact
      perception is influenced by disciplinary culture. Also, trends can be seen
      between respondents' profiles and variables of acceptance and acceptability, and
      certain components of the acceptability judgement are specific to each
      disciplinary culture. The acknowledgment and consideration of these disciplinary
      divergences could allow, among others, for opening up interdisciplinary dialogue
      on matters related to the acceptability of nanomedical applications and their
      developments.

PMID- 25960689
TI  - A novel strategy for utilizing voice coil servoactuators in tensile tests of low
      volume protein hydrogels.
AB  - We present a novel tensile testing system optimized for the mechanical loading of
      microliter volume protein hydrogels. Our apparatus incorporates a voice coil
      servoactuator capable of carrying out fixed velocity extension-relaxation cycles
      as well as extension step protocols. The setup is equipped with an acrylic
      cuvette permitting day-long incubations in solution. To demonstrate the
      functionality of the device, we photochemically crosslinked polyproteins of the
      I91 immunoglobulin domain from the muscle protein titin to create solid hydrogels
      that recapitulate elastic properties of muscle. We present data from tensile
      tests of these low volume biomaterials that support protein unfolding as a main
      determinant of the elasticity of protein hydrogels. Our results demonstrate the
      potential use of protein hydrogels as biomaterials whose elastic properties
      dynamically respond to their environment.

PMID- 25960690
TI  - Morphology, microanatomy and sequence data of Sclerolinum contortum (Siboglindae,
      Annelida) of the Gulf of Mexico.
AB  - Sclerolinum is a small genus of Siboglinidae (Annelida) living in an obligate
      mutualistic association with thiotrophic bacteria as adults. Its taxonomic
      position, based on morphology, has been controversial; however, molecular data
      point to a sister taxa relationship with vestimentiferans. 16S rRNA gene
      sequencing and comparative morphology revealed that the studied population from
      deep-sea hydrocarbon seeps of the Gulf of Mexico belongs to Sclerolinum contortum
      known from the Arctic Sea. Since no anatomical and microanatomical studies have
      been published yet, we conducted such a study on S. contortum using serial
      sectioning and light and transmission electron microscopy. We show that the
      Sclerolinum body, divided into a head, trunk, and opisthosoma, is very similar to
      that of the vestimentiferans, and therefore we propose that the body regions are
      homologous in both taxa.

PMID- 25960692
TI  - Impact of ABCG2 polymorphisms on the clinical outcome of TKIs therapy in Chinese
      advanced non-small-cell lung cancer patients.
AB  - OBJECTIVE: The primary purpose of this study was to investigate the correlation
      between single nucleotide polymorphisms (SNPs) of ATP binding cassette
      superfamily G member 2 (ABCG2) and outcome of tyrosine kinase inhibitions (TKIs)
      therapy in Chinese advanced non-small-cell lung cancer (NSCLC) patients. The
      secondary objective was to identify biomarkers to evaluate the response to
      treatment and outcome of the targeted therapy. METHODS: SNP genotyping (34 G/A,
      421 C/A, 1143 C/T and -15622 C/T) of ABCG2 gene in 100 patients was performed
      using matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry. The clinical characteristics of 100 patients were collected. A
      total of 70 patients were treated with TKIs (gefitinib, erlotinib and icotinib).
      The association between ABCG2 polymorphisms and clinical characteristics was
      evaluated. Kaplan-Meier survival curves were plotted for overall survival (OS)
      and analyzed with the log-rank test. RESULTS: The three polymorphisms of the
      ABCG2 34 G/A, 421 C/A and 1143 C/T occurred more frequently compared with -15622
      C/T in Chinese advanced NSCLC patients. There was no association between ABCG2
      polymorphisms and clinical characteristics (p > 0.05). The median OS of patients
      with GG genotype at position 34 of the ABCG2 gene was significantly shorter than
      those with GA or AA genotype (p < 0.05). No significant difference of OS was
      found in 421 C/A and 1143 C/T polymorphisms (p > 0.05). CONCLUSION: ABCG2 34 G/A
      may be a possible predictor of the clinical outcome of TKIs therapy in NSCLC
      patients.

PMID- 25960691
TI  - MicroRNA (miRNA) in cancer.
AB  - In recent years, there has been a tremendous and growing interest among
      researchers to investigate the role of mircoRNA (miRNA) in normal cellular as
      well as in disease processes. miRNAs are a family of small non-coding RNAs which
      were reported to regulate the expression of various oncogenes or tumor suppressor
      genes. The expression profiling of miRNAs has already entered into cancer clinics
      as diagnostic and prognostic biomarkers to assess tumor initiation, progression
      and response to treatment in cancer patients. This review summarizes: (i) the
      current understanding of interactions between miRNAs and their target genes, (ii)
      recent advances in the regulatory mechanisms that control the expression of genes
      related to carcinogenesis, and (iii) the role of miRNAs in cancer diagnosis and
      therapy. 

PMID- 25960693
TI  - Posttraumatic Stress Disorder after Hurricane Sandy among Persons Exposed to the
      9/11 Disaster.
AB  - BACKGROUND: Traumatic exposure during a hurricane is associated with adverse
      mental health conditions post-event. The World Trade Center Health Registry
      provided a sampling pool for a rapid survey of persons directly affected by
      Hurricane Sandy in the New York City (NYC) metropolitan area in late October
      2012. This study evaluated the relationship between Sandy experiences and Sandy
      related posttraumatic stress disorder (PTSD) among individuals previously exposed
      to the September 11, 2001 (9/11) disaster. METHODS: A total of 4,558 surveys were
      completed from April 10-November 7, 2013. After exclusions for missing data, the
      final sample included 2,214 (53.5%) respondents from FEMA-defined inundation
      zones and 1,923 (46.5%) from non-inundation zones. Sandy exposures included
      witnessing terrible events, Sandy-related injury, fearing for own life or safety
      of others, evacuation, living in a home that was flooded or damaged, property
      loss, and financial loss. Sandy-related PTSD was defined as a score of >=44 on a
      Sandy-specific PTSD Checklist. RESULTS: PTSD prevalence was higher in the
      inundation zones (11.3%) and lower in the non-inundation zones (4.4%). The
      highest prevalence of Sandy-related PTSD was among individuals in the inundation
      zone who sustained an injury (31.2%), reported a history of 9/11-related PTSD
      (28.8%), or had low social support prior to the event (28.6%). In the inundation
      zones, significantly elevated adjusted odds of Sandy-related PTSD were observed
      among persons with a prior history of 9/11-related PTSD, low social support, and
      those who experienced a greater number of Sandy traumatic events. CONCLUSIONS:
      Sandy-related stress symptoms indicative of PTSD affected a significant
      proportion of persons who lived in flooded areas of the NYC metropolitan area.
      Prior 9/11-related PTSD increased the likelihood of Sandy-related PTSD, while
      social support was protective. Public health preparation for events similar to
      Sandy should incorporate outreach and linkages to care for persons with prior
      disaster-related trauma.

PMID- 25960694
TI  - Advances in the Management of Treatment-Resistant Depression.
AB  - : Treatment-resistant depression (TRD) is a prevalent, disabling, and costly
      condition affecting 1%-4% of the U.S. POPULATION:  Current approaches to managing
      TRD include medication augmentation (with lithium, thyroid hormone, buspirone,
      atypical antipsychotics, or various antidepressant medications), psychotherapy,
      and ECT. Advances in understanding the neurobiology of mood regulation and
      depression have led to a number of new potential approaches to managing TRD,
      including medications with novel mechanisms of action and focal brain stimulation
      techniques. This review will define and discuss the epidemiology of TRD, review
      the current approaches to its management, and then provide an overview of several
      developing interventions.

PMID- 25960697
TI  - Peripheral blood film - a review.
AB  - The peripheral blood film (PBF) is a laboratory work-up that involves cytology of
      peripheral blood cells smeared on a slide. As basic as it is, PBF is invaluable
      in the characterization of various clinical diseases. This article highlights the
      basic science and art behind the PBF. It expounds its laboratory applications,
      clinical indications and interpretations in the light of various clinical
      diseases. Despite advances in haematology automation and application of molecular
      techniques, the PBF has remained a very important diagnostic test to the
      haematologist. A good quality smear, thorough examination and proper
      interpretation in line with patient's clinical state should be ensured by the
      haemato-pathologist. Clinicians should be abreast with its clinical utility and
      proper application of the reports in the management of patients. 

PMID- 25960695
TI  - Response to Brosch et al.
AB  - We would like to respond to Brosch et al. regarding our manuscript "Expression of
      the Splicing Factor Gene SFRS10 Is Reduced in Human Obesity and Contributes to
      Enhanced Lipogenesis" (Pihlajamaki et al., 2011b). Brosch performed RT-PCR in
      liver samples from 13 lean and 34 obese individuals, finding no differences in
      SFRS10 or LPIN1 expression. We wish to address points raised by Brosch, including
      experimental strategy and analysis of human SFRS10 expression.

PMID- 25960696
TI  - Correction of precursor and product ion relative abundances in order to
      standardize CID spectra and improve Ecom50 accuracy for non-targeted
      metabolomics.
AB  - Quantitative biases in the abundance of precursor and product ions due to mass
      discrimination in RF-only ion guides results in inaccurate collision induced
      dissociation (CID) spectra. We evaluated the effects of collision cell RF voltage
      and collision energy on CID spectra using ten singly protonated compounds (46-854
      Da) in an orthogonal acceleration time-of-flight mass spectrometer. The relative
      ion transfer efficiency, i.e. the relative amount of ions transferred through the
      ion guide at any particular RF voltage was shown to be dependent on the ion's
      m/z. We developed an algorithm to correct for the mass discriminating effects of
      RF voltage on CID spectra. The algorithm was tested for both precursor and
      product ions at multiple RF voltages and collision energies in order to ensure
      reliability. Our results suggest that compounds that generate major product ions
      with m/z values <150 have peak intensities that deviate substantially from their
      actual abundance. This has implications for small molecule metabolomics research,
      particularly for studies that rely on CID spectra matching methods for structure
      identification.

PMID- 25960698
TI  - Accuracy of nelson and best guess formulae in estimation of weights in nigerian
      children population.
AB  - BACKGROUND: An alternative method of estimating children's weights, when direct
      weighing is impracticable is the use of age-based formulae but these formulae
      have not been validated in Nigeria. This study compares estimated weights from
      two commonly used formulae against actual weights of healthy children. METHODS:
      Children aged 1 month to 11 years (n= 2754) were randomly selected in Ibadan,
      Nigeria using a two-stage sampling procedure. Weight of each child, measured
      using a standard calibrated scale and determined using Nelson and Best Guess
      formulae, were compared. Demographic characteristics were also obtained. Mean
      percentage error (MPE) was calculated and stratified by gender and age. Bland
      Altman graphs were used for visual assessment of the agreement between estimated
      and measured weights. Clinically acceptable MPE was defined as +/-5%. Descriptive
      statistics and paired t test were used to examine the data. Statistical level of
      significance was set at p = 0.05. RESULTS: There were 1349 males and 1405
      females. Nelson and Best Guess formulae overestimated weight by 10.11% (95% CI: 
      20.44, 40.65) in infants. For 1-5 years group, Nelson formula marginally
      underestimated weight by -0.59% (95% CI: -5.16, 3.96) while it overestimated
      weight by 9.87% (95% CI: 24.89, 44.63) in 6-11 years. Best Guess formulae
      consistently overestimated weight in all age groups with the MPE ranging from
      10.11 to 30.67%. CONCLUSION: Nelson and Best Guess formulae are inaccurate for
      weight estimations in infants and children aged 6-11 years. Development of new
      formulae or modifications should be considered for use in the Nigerian children
      population.

PMID- 25960699
TI  - Male knowledge of danger signs of obstetric complications in an urban city in
      South west Nigeria.
AB  - BACKGROUND: Knowledge of danger signs in pregnancy can be regarded as one of the
      ways to eliminate the first level of delay as a factor influencing maternal
      mortality. The role of men as decision makers cannot be overlooked in this
      regard. The aim of this study was to determine men's knowledge of danger signs in
      pregnancy and their role in pregnancy related decision making. METHODS: A cross
      sectional survey was conducted among 259 men aged 15-65 years in selected
      communities in Ibadan, Oyo State by multistage sampling. A semi-structured
      pretested questionnaire was used to obtain information on socio-demographic
      characteristics, attitude and practices concerning antenatal care, knowledge of
      danger signs in pregnancy and decision to seek hospital care. Knowledge of danger
      signs was the main outcome measure categorized into poor and good based on a
      score of <= 6 and > 6. Data were analyzed using descriptive statistics and
      bivariate analysis with level of significance set at 5%. RESULTS: Mean age of
      respondents was 40.4 +/- 11.4 years. Almost half had at least secondary education
      (47.5%) and were mainly artisans by occupation (59.8%), while 18.1% could not
      mention any danger sign. Majority had poor knowledge about danger signs in
      pregnancy (60.6%). There was no significant difference in knowledge of
      respondents within different age groups, by occupation, number of children and
      from different educational levels. CONCLUSION: Poor knowledge of obstetric danger
      signs was evident among these men. Programmes targeted at providing education
      about danger signs in pregnancy for men are recommended.

PMID- 25960700
TI  - Non-glaucomatous optic neuropathy in ibadan: extrapolations to healthcare funding
      in Nigeria.
AB  - BACKGROUND: Optic neuropathy is not a diagnosis in itself, as potential
      aetiologies are myriad. A pilot study conducted in the Eye Clinic, University
      College Hospital, Ibadan, between September 2007 and November 2009, showed that
      46.8% of new cases presenting to the neuroophthalmology unit, had non
      glaucomatous optic neuropathy (NGON) in which, the precise aetiology of optic
      neuropathy was never diagnosed. METHODS: All cases of NGON, seen in the neuro
      ophthalmology unit, between September 2007 and June 2014 were analyzed to
      determine common aetiologies and identify the difficulties encountered in their
      investigation or management. RESULTS: There were 159 cases of NGON. The age range
      was 6 months to 87 years (mean 39.0, SD 21.3). Male: Female ratio was 1.2: 1, and
      the commonest diagnosis was optic atrophy of unknown aetiology. Challenges
      identified included difficulty obtaining recommended radiological and serological
      investigations, as well as no access to genetic studies and high loss to follow
      up. CONCLUSION: There are major constraints in the investigation of patients
      presenting with optic nerve disease in Ibadan, despite the prevalence of NGON as
      a major cause of visual disability among neuro-ophthalmic patients in this
      setting. Diagnostic constraints must be addressed, to facilitate
      neuroophthalmology patient care, within our limited resources.

PMID- 25960701
TI  - Aging affects morphology but not stimulated secretion of saliva in rats.
AB  - BACKGROUND: The role of aging on the salivary gland function still remains
      controversial and inconclusive. This study was undertaken to determine the
      effects of aging on the morphology and secretion of salivary glands using male
      Wistar rats. METHOD: There were three age groups; group A (3 months old; n = 8),
      group B (6 months old; n = 8), and group C (9 months old; n = 8). Body weights,
      salivary gland weights, salivary flow rates, pH and salivary levels of sodium,
      potassium, calcium, chloride, bicarbonate, phosphate and total protein were
      measured and compared. Hematoxylin-eosin stained histological slides of the
      salivary glands were assessed for morphological changes. RESULTS: Body weights
      increased with age while mean parotid gland weight was significantly higher in
      group B than in groups A and C. Mean salivary flow rate was significantly higher
      in group B and C than in group A, and mean salivary pH was significantly higher
      in group B and C than group A. Analysis of salivary electrolytes and total
      protein showed that mean levels of sodium, potassium and bicarbonate increased
      with age significantly while mean levels of calcium, chloride, phosphate and
      total protein did not show significant change among the groups. CONCLUSION: These
      findings showed that varying changes were observed in the morphology of salivary
      glands of aging rats without impaired function.

PMID- 25960702
TI  - Periapical lesions of the jaws: a review of 104 cases in ibadan.
AB  - BACKGROUND: Periapical lesions (PLs) occur as a result of pulpal inflammation and
      may rarely be seen in the absence of pulpal diseases. They are the most common
      pathological lesions affecting the alveolar bone. OBJECTIVE: This study aims to
      describe the clinicopathological features of PLs of the jaws with emphasis on the
      two most common types. METHODS: Histopathology records of PLs diagnosed from
      January 1990 to December 2012 at the Department of Oral Pathology, University
      College Hospital Ibadan, were examined and categorized into periapical cysts
      (PCs); periapical granuloma (PGs) and others. Clinical data and histopathological
      features of these PLs were reviewed and analyzed. RESULTS: One hundred and four
      lesions met the criteria for this study and consisted of PGs with 71 (68.3%)
      cases and PCs with 31 (29.8%) cases and one case each of apical scar and
      pleomorphic adenoma. Age range of cases was 9 to 80 years (mean=35.6 +/-
      15.8years) with a peak at age group of 20-29 years. Females were more frequently
      affected with 51.9% of cases. PLs were most frequently diagnosed in the anterior
      maxillary region with 58 (56.9%) cases, while the most frequently involved tooth
      was the left maxillary central incisor with 23 (22.1%) cases. CONCLUSION:
      Findings in this study are consistent with those of previous studies. It is
      important for all periapical pathological specimens to be submitted for
      histological examination to establish an accurate diagnosis and aid in the
      identification of sinister lesions that may present in the Periradicular region
      of teeth.

PMID- 25960704
TI  - Enhanced Therapeutic Epidermal Growth Factor Receptor (EGFR) Antibody Delivery
      via Pulsed Ultrasound with Targeting Microbubbles for Glioma Treatment.
AB  - Pulsed-mode ultrasound (pUS) in combination with intravenously (IV) administered
      microbubbles (MBs) can enhance local drug delivery by temporarily enhancing
      capillary permeability. This study evaluates the use of epidermal growth factor
      receptor (EGFR)-targeting MBs after pUS treatment to enhance the effects of
      therapeutic-EGFR antibody delivery to glioma tumor cells in mice. Three animal
      groups were compared: (1) IV-injected non-targeting MBs, (2) IV-injected
      targeting MBs, and (3) IV-injected targeting MBs combined with pUS treatment. All
      animals were analyzed using high-frequency small-animal US imaging. The mean
      halftime of circulating targeting MBs was significantly increased from 3.13 min
      of targeting bubble alone to 5.86 min by targeting MBs combined with pUS
      treatment, compared to 2.34 min for non-targeting MBs. Compared to targeting
      bubble administration alone, pUS exposure prior to injection of targeting MBs was
      also significantly better at suppressing tumor growth when monitored for up to 35
      days (p < 0.05). The final relative tumor volumes were 2664, 700, and 188 mm3 for
      non-targeting MBs, targeting MBs, and targeting MBs combined with pUS treatment,
      respectively. pUS treatment prolonged the mean circulatory halftime of targeting
      MBs and enhanced the anti-tumor effect of EGFR antibodies in a human glioma model
      in mice. Targeting MBs combined with pUS treatment thus has potential for
      enhanced therapeutic antibody delivery for facilitating anti-glioma treatment.

PMID- 25960703
TI  - Anti-fouling Coatings of Poly(dimethylsiloxane) Devices for Biological and
      Biomedical Applications.
AB  - Fouling initiated by nonspecific protein adsorption is a great challenge in
      biomedical applications, including biosensors, bioanalytical devices, and
      implants. Poly(dimethylsiloxane) (PDMS), a popular material with many attractive
      properties for device fabrication in the biomedical field, suffers serious
      fouling problems from protein adsorption due to its hydrophobic nature, which
      limits the practical use of PDMS-based devices. Effort has been made to develop
      biocompatible materials for anti-fouling coatings of PDMS. In this review,
      typical nonfouling materials for PDMS coatings are introduced and the associated
      basic anti-fouling mechanisms, including the steric repulsion mechanism and the
      hydration layer mechanism, are described. Understanding the relationships between
      the characteristics of coating materials and the accompanying anti-fouling
      mechanisms is critical for preparing PDMS coatings with desirable anti-fouling
      properties.

PMID- 25960705
TI  - Electromyography-Based Quantitative Representation Method for Upper-Limb Elbow
      Joint Angle in Sagittal Plane.
AB  - This paper presents a quantitative representation method for the upper-limb elbow
      joint angle using only electromyography (EMG) signals for continuous elbow joint
      voluntary flexion and extension in the sagittal plane. The dynamics relation
      between the musculotendon force exerted by the biceps brachii muscle and the
      elbow joint angle is developed for a modified musculoskeletal model. Based on the
      dynamics model, a quadratic-like quantitative relationship between EMG signals
      and the elbow joint angle is built using a Hill-type-based muscular model.
      Furthermore, a state switching model is designed to stabilize the transition of
      EMG signals between different muscle contraction motions during the whole
      movement. To evaluate the efficiency of the method, ten subjects performed
      continuous experiments during a 4-day period and five of them performed a
      subsequent consecutive stepping test. The results were calculated in real-time
      and used as control reference to drive an exoskeleton device bilaterally. The
      experimental results indicate that the proposed method can provide suitable
      prediction results with root-mean-square (RMS) errors of below 10 degrees  in
      continuous motion and RMS errors of below 10 degrees  in stepping motion with 20
      degrees  and 30 degrees  increments. It is also easier to calibrate and
      implement.

PMID- 25960706
TI  - Classification of Benign and Malignant Breast Tumors in Ultrasound Images with
      Posterior Acoustic Shadowing Using Half-Contour Features.
AB  - Posterior acoustic shadowing (PAS) can bias breast tumor segmentation and
      classification in ultrasound images. In this paper, half-contour features are
      proposed to classify benign and malignant breast tumors with PAS, considering the
      fact that the upper half of the tumor contour is less affected by PAS. Adaptive
      thresholding and disk expansion are employed to detect tumor contours. Based on
      the detected full contour, the upper half contour is extracted. For breast tumor
      classification, six quantitative feature parameters are analyzed for both full
      contours and half contours, including standard deviation of degree (SDD), which
      is proposed to describe tumor irregularity. Fifty clinical cases (40 with PAS and
      10 without PAS) were used. Tumor circularity (TC) and SDD were both effective
      full- and half-contour parameters in classifying images without PAS. Half-contour
      TC [74 % accuracy, 72 % sensitivity, 76 % specificity, 0.78 area under the
      receiver operating characteristic curve (AUC), p > 0.05] significantly improved
      the classification of breast tumors with PAS compared to that with full-contour
      TC (54 % accuracy, 56 % sensitivity, 52 % specificity, 0.52 AUC, p > 0.05). Half
      contour SDD (72 % accuracy, 76 % sensitivity, 68 % specificity, 0.81 AUC, p <
      0.05) improved the classification of breast tumors with PAS compared to that with
      full-contour SDD (62 % accuracy, 80 % sensitivity, 44 % specificity, 0.61 AUC, p
      > 0.05). The proposed half-contour TC and SDD may be useful in classifying benign
      and malignant breast tumors in ultrasound images affected by PAS.

PMID- 25960707
TI  - Obesity and older age as protective factors for vaginal cuff dehiscence following
      total hysterectomy.
AB  - Studies have shown an increased risk of vaginal cuff dehiscence following total
      laparoscopic hysterectomy (TLH). Patient variables associated with dehiscence
      have not been well described. This study aims to identify factors associated with
      dehiscence following varying routes of total hysterectomy. This is a
      retrospective, matched, case-control study of women who underwent a total
      hysterectomy at a large, urban, university-based teaching hospital from January
      2000 to December 2011. Women who underwent a total hysterectomy and had a
      dehiscence (n = 31) were matched by surgical mode to the next five total
      hysterectomies (n = 155). Summary statistics and conditional logistic regression
      were performed to compare cases to controls. Obese women (BMI >= 30) were 70 %
      less likely than normal weight women (BMI < 25) to experience a dehiscence (p =
      0.02). When stratified by hysterectomy route, obese women were 86 % less likely
      to have a dehiscence following robotic-assisted total hysterectomy (RAH) and TLH
      than normal weight women (p = 0.04). Further, increasing age was protective of
      dehiscence in this subgroup of women (p = 0.02). Older age and obesity were
      associated with a decreased risk of dehiscence following RAH and TLH but not
      following other routes. Increased risk of dehiscence following TLH observed in
      previous studies may be partially due to patient characteristics.

PMID- 25960708
TI  - Cross-linked xenogenic collagen implantation in the sheep model for vaginal
      surgery.
AB  - The properties of meshes used in reconstructive surgery affect the host response
      and biomechanical characteristics of the grafted tissue. Whereas durable
      synthetics induce a chronic inflammation, biological grafts are usually
      considered as more biocompatible. The location of implantation is another
      determinant of the host response: the vagina is a different environment with
      specific function and anatomy. Herein, we evaluated a cross-linked acellular
      collagen matrix (ACM), pretreated by the anti-calcification procedure ADAPT(r) in
      a sheep model for vaginal surgery. Ten sheep were implanted with a cross-linked
      ACM, and six controls were implanted with a polypropylene (PP; 56 g/m2) control.
      One implant was inserted in the lower rectovaginal septum, and one was used for
      abdominal wall defect reconstruction. Grafts were removed after 180 days; all
      graft-related complications were recorded, and explants underwent bi-axial
      tensiometry and contractility testing. Half of ACM-implanted animals had palpable
      induration in the vaginal implantation area, two of these also on the abdominal
      implant. One animal had a vaginal exposure. Vaginal ACMs were 63 % less stiff
      compared to abdominal ACM explants (p = 0.01) but comparable to vaginal PP
      explants. Seven anterior vaginal ACM explants showed areas of graft degradation
      on histology. There was no overall difference in vaginal contractility.
      Considering histologic degradation in the anterior vaginal implant as
      representative for the host, posterior ACM explants of animals with degradation
      had a 60 % reduced contractility as compared to PP (p = 0.048). Three abdominal
      implants showed histologic degradation; those were more compliant than non
      degraded implants. Vaginal implantation with ACM was associated with graft
      related complications (GRCs) and biomechanical properties comparable to PP.
      Partially degraded ACM had a decreased vaginal contractility.

PMID- 25960709
TI  - Frequency and specificity of red blood cell alloimmunization in chilean
      transfused patients.
AB  - BACKGROUND: Alloimmunization is an adverse effect of blood transfusions. In
      Chile, alloimmunization frequency is not established, and for this reason the aim
      of this study was to investigate the prevalence and specificity of red blood cell
      (RBC) alloantibodies in Chilean transfused subjects. METHODS: Records from 4,716
      multi-transfused patients were analyzed. In these patients, antibody screening
      was carried out prior to cross-matching with a commercially available two-cell
      panel by the microcolum gel test, and samples with a positive screen were
      analyzed for the specificity of the alloantibody with a 16-cell identification
      panel. RESULTS: The incidence of RBC alloimmunization in transfused patients was
      1.02% (48/4,716) with a higher prevalence in women (40/48). We detected 52
      antibodies, the most frequent specificities identified were anti-E (30.8%), anti
      K (26.9%), anti-D (7.7%), and anti-Fy(a) (5.8%). The highest incidence of
      alloantibodies was observed in cancer and gastroenterology patients. CONCLUSION:
      The data demonstrated a low alloimmunization frequency in Chilean transfused
      patients, principally associated with antibodies anti-E, anti-K, anti-D, and anti
      Fy(a).

PMID- 25960710
TI  - Transfusion management and immunohematologic complications in liver
      transplantation: experience of a single institution.
AB  - OBJECTIVE: Liver transplantation (LT) has traditionally been associated with
      major blood loss and consequently high blood transfusion requirements. Our
      objective was to analyze transfusion management and incidence of
      immunohematologic complications in patients undergoing LT at our institution.
      METHODS: A retrospective analysis of immunohematologic events and transfusion
      outcomes was carried out at La Fe University Hospital in Valencia. Data from 654
      patients were reviewed: 654 underwent only one LT while 36 underwent second LT.
      RESULTS: Patients received a median of 3 red blood cell (RBC) concentrates, 2
      platelets concentrates (PCs) and 2 fresh frozen plasma units (FFPs). Variables
      significantly influencing RBC transfusions were: the MELD score, hemoglobin
      levels, and the platelet counts before LT. 27 patients (4.1%) had a positive
      antibody screening before transplant. Immunohematologic events occurred in 8% of
      the patients, mostly in the first month after LT, and involved hemolysis in 13
      cases. Mortality was significantly higher in patients developing
      immunohematologic disorders (42.8 vs. 18.3%; p < 0.001). In the multivariable
      analysis, only ABO minor incompatibility between donor and recipient
      significantly increased the appearance of immunohematologic incidences (OR 4.92,
      95% CI 2.31-10.50; p < 0.001). CONCLUSION: Transfusion management of patients
      that underwent LT can be complicated by immunohematologic problems. Blood banks
      should implement the DAT test in each transfusion to detect them.

PMID- 25960711
TI  - Prospective Evaluation of a Transfusion Policy of RhD-Positive Red Blood Cells
      into DEL Patients in China.
AB  - BACKGROUND: The D antigen is highly immunogenic, requiring only a small quantity
      of transfused red blood cells (RBCs) to cause alloimmunization in D-
      immunocompetent recipients. DEL was reported arousing alloimmunization to true Rh
      patients. Molecular studies of the RHD gene have revealed that DEL individuals
      retain a grossly intact RHD gene or have a portion of RHD in their genomes.
      Avoiding immunization with clinically important antibodies is a primary objective
      in transfusion medicine. METHODS: In order to determine whether pregnant DEL
      women carrying an RhD+ fetus are at risk of anti-D alloimmunization, 808 Rh-
      pregnant women with a history of gestations or parturitions who regularly visited
      hospitals for their prenatal anti-D screening and postpartum care from January
      2011 to December 2012 were investigated. Samples were analyzed for DEL by PCR
      with specific primers, PCR-sequence-specific primers (PCR-SSP), reverse
      transcription-PCR (RT-PCR), PCRrestriction fragment length polymorphism (PCR
      RFLP), and by gene sequencing to characterize different alleles. RESULTS: Among
      the 808 Rh- pregnant women of our sample, 178 (22.0%) were typed as DEL; 168 DEL
      samples were confirmed to have the RHD (1,227 G>A) allele, 8 DEL samples were
      characterized by one base mutation of the RHD (3G >A) allele, and the remaining
      two DEL samples were determined to carry RHD-CE(4-9)-D or RHD-CE(2-5)-D. The
      observation of allo-anti-D in two prominent D epitope loss cases confirmed the
      partial nature of these DEL phenotypes. CONCLUSIONS: In conclusion, evidence is
      provided that different DEL genotypes code either for partial or complete D
      antigen expression. It is suggested that the use of RhD+ RBCs in complete D
      antigen DEL patients does not induce adverse reaction.

PMID- 25960712
TI  - Non-Invasive Prenatal RHD Genotyping Using Cell-Free Fetal DNA from Maternal
      Plasma: An Italian Experience.
AB  - BACKGROUND: This study assessed the diagnostic accuracy of a non-invasive
      approach to fetal RHD genotyping using cell-free fetal DNA in maternal plasma and
      a combination of methodological strategies. METHODS: Real-time PCR (qPCR) was
      performed on 216 RhD-negative women between weeks 10+0 and 14+6 of gestation (1st
      qPCR). qPCR was repeated (2nd qPCR) to increase the amount of each sample for
      analysis, on 95 plasma aliquots that were available from first trimester blood
      collection (group 1) and on 13 samples that were collected between weeks 18+0 and
      25+6 of gestation (group 2). qPCR was specific for exons 5 and 7 of the RHD gene
      (RHD5 and RHD7). The results were interpreted according to the number of positive
      replicates of both exons. RESULTS: 1st qPCR: diagnostic accuracy was of 93.3%.
      Diagnostic accuracy increased from 90.5% (1st qPCR) to 93.7% (2nd qPCR) in group
      1 and from 84.6% (1st qPCR) to 92.3% (2nd qPCR) in group 2. These increments were
      not statistically significant. CONCLUSION: Our approach to RHD genotyping in
      early pregnancy yielded high diagnostic accuracy. Increasing the amount of DNA
      analyzed in each sample did not improve significantly the diagnostic accuracy of
      the test.

PMID- 25960713
TI  - Beta-Chemokine CCL15 Affects the Adhesion and Migration of Hematopoietic
      Progenitor Cells.
AB  - BACKGROUND: Hematopoietic stem and progenitor cell (HPC) motility is essential
      for HPC transplantation. The chemokine CXCL12 is key for HPC motility. Further
      regulators are of interest to improve HPC transplantation and regenerative
      medicine. Here the impact of the human chemokine CCL15 on HPC motility was
      investigated. METHODS: CCL15 plasma concentrations were determined during HPC
      mobilization in humans. Activity of CCL15 on HPCs was investigated in murine
      assays, including chemotaxis, adhesion, and CFU-A assays, and competitive
      repopulation assays. RESULTS: During HPC mobilization with granulocyte colony
      stimulating factor, blood plasma contains increased concentrations (1.1 +/- 0.1
      ng/ml) of activated CCL15(27-92) versus 0.4 +/- 0.1 ng/ml in controls (p = 0.02).
      CCL15(27-92) significantly enhanced CXCL12-induced transwell migration of Lin
      /Sca1+ HPCs and strengthened shear stress-dependent adhesion to vascular cell
      adhesion molecule-1 (VCAM-1). CCL15(27-92) dose-dependently reduced the colony
      size in CFU-A assays performed with murine bone marrow and Lin-/Sca1+ HPCs.
      CCL15(27-92) did not show a direct impact on cell cycle status of HPCs. In murine
      repopulation assays, pretreatment of bone marrow with CCL15(27-92) significantly
      increased competitive repopulation. CONCLUSION: Our results point to a regulation
      of HPCs by CCL15 by modulating migratory and adhesive properties of HPCs with the
      potency to improve HPC short-term engraftment in stem cell transplantation.

PMID- 25960714
TI  - Monitoring of hematopoietic chimerism by real-time quantitative PCR of micro
      insertions/deletions in samples with low DNA quantities.
AB  - BACKGROUND: Sensitive and accurate methods to detect hematopoietic chimerism
      after hematopoietic stem cell transplantation (HSCT) are essential to evaluate
      engraftment and to monitor response to therapeutic procedures such as donor
      lymphocyte infusion. Continuous long-term follow up, however, requires large
      amounts of pre-HSCT samples limiting the application of many widely used
      techniques for sensitive chimerism monitoring. METHODS: DNAs from 42 normal
      healthy donors and 16 HSCT donor/recipient pairs were employed to validate the
      use of allele-specific insertion/deletion (indel) quantitative real-time
      polymerase chain reaction (qPCR) to quantify chimerism in samples with low
      amounts of DNA. Consequently, indel-qPCR analyses of samples from 16 HSCT
      patients were compared to short-tandem repeat (STR) specific PCR analyses.
      RESULTS: Typing with reduced amounts of input DNA (15 vs. 60 ng) allowed for the
      reliable distinction of positive (mean threshold cycle (ct) 28.05) and negative
      (ct >36) signals. The high informativity of primer/probe sets, with 12 out of 19
      markers exceeding 20% informativity, was confirmed in our cohort (n = 74).
      Importantly, a fourfold reduction of input DNA compared to published protocols
      did not alter PCR efficiencies and allowed for a more sensitive detection of
      chimerism in 7 of 16 HSCT patients compared to results obtained by STR-PCR.
      CONCLUSIONS: Our data suggest that indel-qPCR is a more sensitive technique for
      the detection of hematopoietic chimerism compared to STR-PCR and works
      efficiently for samples with low amounts of DNA.

PMID- 25960715
TI  - Biochemical and cellular changes in leukocyte-depleted red blood cells stored for
      transfusion.
AB  - BACKGROUND: To evaluate biochemical and cellular changes associated with the
      storage of leukocyte-depleted red blood cells (RBCs). METHODS: We investigated 10
      leukocyte-depleted RBC units, randomly chosen from volunteer donors. Every week
      an aliquot was collected for laboratorial evaluation, which included complete
      cell blood count, glucose-6-phosphate dehydrogenase (G6PD) activity,
      extracellular sodium, potassium and pH, membrane-bound hemoglobin (MBH), band 3
      profile, and quantification of RBC membrane proteins composition. RESULTS: We
      observed an increase in mean cell volume (from 91.86 +/- 4.65 fl to 98.10 +/-
      5.80 fl, day 0 vs. day 21; p < 0.05), red cell distribution width, percentage of
      macrocytic RBCs, reticulocyte hemoglobin content and a decreased percentage of
      microcytic RBCs, mean cell volume concentration and G6PD activity. The
      extracellular concentration of sodium decreased, and that of potassium increased
      significantly over time. RBC membrane composition revealed an increase in
      spectrin/ankyrin ratio after 21 days (from 4.84 +/- 0.99 to 5.27 +/- 0.94, day 0
      vs. day 21; p < 0.05). At day 35, a decrease in ankyrin (from 6.44 +/- 1.70% to
      5.49 +/- 1.96%, day 0 vs. day 35; p < 0.05), in protein 4.1/band 3, protein
      4.2/band 3, and ankyrin/band 3 ratios and in band 5 was observed. CONCLUSIONS:
      Our data show that leukocyte-depleted RBCs present changes in the RBC morphology,
      membrane protein composition, enzymatic activity, and extracellular electrolyte
      concentration and pH.

PMID- 25960716
TI  - Molecular Basis of KELnull Phenotype in Brazilians.
AB  - BACKGROUND: KELnull (K0) persons can produce clinically significant anti-KEL5
      antibody after transfusion and/or pregnancy, requiring K0 blood transfusion when
      indicated. 37 K0 alleles have been reported in studies over different
      populations, but none in Amerindian-Caucasian descendants from South America. The
      aim of this study was to identify the molecular basis of K0 phenotype in
      Brazilians. METHODS: We investigated three K0 samples from different Brazilian
      blood banks (Recife, Manaus, and Vila Velha) in women with anti-KEL5. KEL antigen
      typing was performed by serologic techniques, and the K0 status was confirmed by
      flow cytometry. PCR-RFLP and DNA sequencing of the KEL coding and exon-intron
      regions were also performed. RESULTS: RBCs of the 3 patients were phenotyped as
      KEL:-1,-2,-3,-4,-7. The 3 patients had the same KEL*02/02 genotype and were
      negative for KEL*02.03 and KEL*02.06 alleles. The Recife K0 patient was
      homozygous for IVS16 + 1g>a mutation (KEL*02N.31 allele). The flow cytometry with
      anti-KEL1, anti-KEL2, anti-KEL3, anti-KEL4, and anti-CD238 confirmed the K0
      phenotype. In addition, we found the c.10423C>T mutation (KEL*02N.04 allele) in
      both the Manaus K0 and the Vila Velha K0 patients. CONCLUSION: This report
      represents the first study of K0 molecular basis performed in Amerindian
      Caucasian descendants from South America.

PMID- 25960717
TI  - A Unique Case Involving a Female Patient with Upshaw-Schulman Syndrome: Low
      Titers of Antibodies against ADAMTS13 prior to Pregnancy Disappeared after
      Successful Delivery.
AB  - BACKGROUND: Upshaw-Schulman syndrome (USS) is usually suspected based on severe
      deficiency of ADAMTS13 activity without ADAMTS13 antibody, but the definitive
      diagnosis is made by ADAMTS13 gene analysis. We present a unique case of USS with
      low titers of ADAMTS13 antibodies before pregnancy. Interestingly, titers of
      ADAMTS13 antibodies decreased to almost undetectable levels after delivery. CASE
      REPORT: In patient LL4, the diagnosis of USS was confirmed at age 27 by ADAMTS13
      gene analysis. She became pregnant at age 30. During the pregnancy, she received
      regular fresh frozen plasma (FFP) infusion. Plasma von Willebrand factor levels
      increase as pregnancy progresses. To prevent platelet thrombi, much more ADAMTS13
      supplementation is necessary during late gestation in patients with USS.
      Therefore, we shortened the interval between and increased the volume of FFP
      infusions as pregnancy progressed. At 39 weeks, she delivered a healthy baby
      girl. Before pregnancy, she had low titers of both neutralizing and binding anti
      ADAMTS13 antibodies. Despite frequent FFP infusions, titers of the antibodies did
      not increase, but rather decreased to almost undetectable levels during
      pregnancy. CONCLUSION: Both the neutralizing and binding antibodies against
      ADAMTS13 decreased to almost undetectable levels after delivery in this patient,
      which can be caused by an immunological reset.

PMID- 25960718
TI  - New avenues in secondary and tertiary prevention of breast cancer.

PMID- 25960719
TI  - Breast cancer risks and risk prediction models.
AB  - BRCA1/2 mutation carriers have a considerably increased risk to develop breast
      and ovarian cancer. The personalized clinical management of carriers and other at
      risk individuals depends on precise knowledge of the cancer risks. In this
      report, we give an overview of the present literature on empirical cancer risks,
      and we describe risk prediction models that are currently used for individual
      risk assessment in clinical practice. Cancer risks show large variability between
      studies. Breast cancer risks are at 40-87% for BRCA1 mutation carriers and 18-88%
      for BRCA2 mutation carriers. For ovarian cancer, the risk estimates are in the
      range of 22-65% for BRCA1 and 10-35% for BRCA2. The contralateral breast cancer
      risk is high (10-year risk after first cancer 27% for BRCA1 and 19% for BRCA2).
      Risk prediction models have been proposed to provide more individualized risk
      prediction, using additional knowledge on family history, mode of inheritance of
      major genes, and other genetic and non-genetic risk factors. User-friendly
      software tools have been developed that serve as basis for decision-making in
      family counseling units. In conclusion, further assessment of cancer risks and
      model validation is needed, ideally based on prospective cohort studies. To
      obtain such data, clinical management of carriers and other at-risk individuals
      should always be accompanied by standardized scientific documentation. 

PMID- 25960720
TI  - Intensified surveillance for early detection of breast cancer in high-risk
      patients.
AB  - Efforts for early detection of breast cancer play an important role in the care
      of high-risk women. This will include both women with a pathological mutation in
      one of the known breast cancer susceptibility genes as well as women with a high
      breast cancer risk based on family history only. Due to the much higher incidence
      of breast cancer in premenopausal women with a genetic predisposition or a
      familial background, to be most effective, imaging-based breast surveillance
      should start at an age as early as 25-30 years. There is now ample evidence that
      magnetic resonance imaging (MRI) is by far the most sensitive imaging modality in
      young high-risk women. With high-risk multimodality screening at least 30% of
      breast cancers will be detected primarily by MRI and would have been missed at
      regular screening without MRI. Therefore, most high-risk breast surveillance
      programs now offer annual MRI to eligible high-risk women from age 25 to 30,
      usually supplemented by regular mammography starting at least from age 40. The
      inclusion of clinical breast exam (CBE) and/or ultrasound in the high-risk
      surveillance has little impact on the detection of additional cancers, but may
      improve compliance and reduce unnecessary callbacks for nonspecific findings on
      MRI. To reduce advanced stage interval cancers, especially in BRCA1/2 mutation
      carriers, some programs offer additional semiannual CBE and/or ultrasound or
      alternate MRI and mammography every 6 months. How long regular MRI should be
      continued in high-risk women is a matter of considerable debate. It appears
      feasible that MRI can safely be discontinued even in BRCA1/2 mutation carriers
      between the age of 60 and 70, especially if mammographic breast density is low.
      Even though several cohort studies have now demonstrated a very favorable stage
      distribution of breast cancers found in women undergoing high-risk surveillance
      with MRI, data on long-term survival and mortality in these patients is still
      rare. 

PMID- 25960721
TI  - Genotype/Phenotype correlations in patients with hereditary breast cancer.
AB  - Of all breast cancer cases, 5-10% can be attributed to germline mutations, and
      the high-susceptibility genes BRCA1 and BRCA2 account for about 25-28% of these
      cases. For the remainder, several genes of moderate and low penetrance have been
      discovered. Histopathologic characteristics have been studied in small cohorts,
      but for most of the known non-BRCA1/2-associated hereditary breast cancers, the
      histologic and immunohistochemical phenotypes are not yet identified.
      Particularly BRCA1 tumors are associated with a distinct morphology and
      immunohistochemical characteristics that differ from sporadic breast cancer of
      age-matched controls. The recognition of features characteristic of these
      mutations can be helpful to identify patients likely to carry a germline mutation
      and to assess which gene should be screened for first, in families with a high
      occurrence of breast and ovarian cancer. 

PMID- 25960722
TI  - Familial breast cancer - targeted therapy in secondary and tertiary prevention.
AB  - The introduction of an increasing number of individualized molecular targeted
      therapies into clinical routine mirrors their importance in modern cancer
      prevention and treatment. Well-known examples for targeted agents are the
      monoclonal antibody trastuzumab and the selective estrogen receptor modulator
      tamoxifen. The identification of an unaltered gene in tumor tissue in colon
      cancer (KRAS) is a predictor for the patient's response to targeted therapy with
      a monoclonal antibody (cetuximab). Targeted therapy for hereditary breast and
      ovarian cancer has become a reality with the approval of olaparib for platin
      sensitive late relapsed BRCA-associated ovarian cancer in December 2014. This
      manuscript reviews the status quo of poly-ADP-ribose polymerase inhibitors
      (PARPi) in the therapy of breast and ovarian cancer as well as the struggle for
      carboplatin as a potential standard of care for triple-negative and, in
      particular, BRCA-associated breast cancer. Details of the mechanism of action
      with information on tumor development are provided, and an outlook for further
      relevant research is given. The efficacy of agents against molecular targets
      together with the identification of an increasing number of cancer-associated
      genes will open the floodgates to a new era of treatment decision-making based on
      molecular tumor profiles. Current clinical trials involving patients with BRCA
      associated cancer explore the efficacy of the molecular targeted therapeutics
      platinum and PARPi. 

PMID- 25960723
TI  - Imaging-histological discordance after sonographically guided percutaneous breast
      core biopsy.
AB  - BACKGROUND: The objectives of this study were to determine the frequency of
      imaging-histological discordance and to compare the frequency of carcinoma
      between discordant lesions at ultrasound (US)-guided core needle biopsy.
      MATERIALS AND METHODS: From November 2009 to June 2012, we performed US-guided 14
      gauge core needle biopsies on 989 breast lesions in 961 women. We reviewed 58
      (5.8%) cases that had imaging-histological discordance after percutaneous breast
      biopsy and underwent subsequent excisional biopsy. The clinical, radiological,
      and histological findings were reviewed for those 58 cases. RESULTS: Among the 58
      cases, subsequent excisions revealed 16 (27.5%) malignancies, which were
      categorized as 9 (15.5%) invasive ductal carcinomas, 4 (6.9%) malignant phyllodes
      tumors, and 3 (5.1%) ductal carcinomas in situ. CONCLUSION: The malignancy rate
      of 27.5% suggests that surgical excision should be performed in those cases
      presenting with imaging-histological discordance after US-guided core biopsy.
      Careful correlation of clinical, radiological, and histological results as well
      as appropriate follow-up are essential. We have submitted a short version of this
      work as a poster presentation during the 2012 European Society of Surgery (ESS)
      Congress in Istanbul/Turkey.

PMID- 25960724
TI  - Patients' perspective on day case breast surgery.
AB  - BACKGROUND: This study assessed the views of patients undergoing breast surgery
      for breast cancer with a planned overnight stay, asking whether they would be
      happy to be discharged home on the same day of surgery. METHODS: A structured
      questionnaire sent out in the 6 weeks following surgery was used to ascertain the
      patients' views. RESULTS: The majority of patients undergoing mastectomy and
      axillary node clearance preferred an overnight stay, primarily for psychological
      reasons. CONCLUSIONS: Patients undergoing breast-conserving surgery were more
      prepared to go home on the day of surgery.

PMID- 25960725
TI  - Tumor Bed Boost Integration during Whole Breast Radiotherapy: A Review of the
      Current Evidence.
AB  - Radiation therapy delivered with hypofractionation, which involves the delivery
      of a higher dose per fraction in fewer fractions (generally with a lower total
      nominal dose) over a shorter overall treatment time, is an established
      therapeutic option at least for a selected group of early breast cancer patients
      after breast-conserving surgery. Optimal delivery of the tumor bed boost dose in
      terms of timing, fractionation, and total dose whenever a hypofractionated
      schedule is employed has yet to be established. We herein present a review of the
      current evidence on the role of boost integration in whole breast radiotherapy. 

PMID- 25960726
TI  - Chronic granulomatous inflammation of the breast as a first clinical
      manifestation of primary sarcoidosis.
AB  - BACKGROUND: Sarcoidosis is an idiopathic multisystemic disease that affects young
      to middle aged adults, with higher incidence in women. Although it may involve
      the breast parenchyma, primary sarcoidosis of the breast is very rare. It occurs
      in less than 1% of cases. In a differential diagnosis it may potentially be
      considered a malignancy. CASE REPORT: We report a case in which breast
      sarcoidosis was the first clinical manifestation of systemic disease in a 54-year
      old woman who presented with wide erythematous skin changes associated with
      palpable induration. Considering the fact that physical examination and the
      results of mammography, ultrasound and magnetic resonance imaging were
      inconclusive and unable to rule out malignancy, biopsy was performed.
      Pathohistological diagnosis showed a non-necrotizing granulomatous inflammation
      without elements of breast cancer. Sarcoidosis was confirmed with elevated level
      of angiotensin-converting enzyme in the sera and characteristic chest multislice
      computed tomography findings. The bronchoalveolar lavage was infiltrated with
      lymphocytes. CONCLUSION: Breast sarcoidosis has diverse and nonspecific imaging
      characteristics. Carcinoma must always be excluded by core needle biopsy.
      Achieving correct diagnosis is mandatory so that adequate corticosteroid therapy
      can be applied as early as possible. A multidisciplinary approach is of utmost
      importance in the diagnostic workup.

PMID- 25960727
TI  - BCY 2 - Second Breast Cancer in Young Women Conference 4th-5th November 2014
      Dublin, Ireland.

PMID- 25960728
TI  - Surgery for Severe Ulcerative Colitis during Pregnancy: Report of Two Cases.
AB  - Refractory ulcerative colitis (UC) that does not respond to medical therapy often
      requires surgery even during pregnancy. Although surgical cases of UC during
      pregnancy were reported previously, the standard surgical strategy for both
      colitis and pregnancy was unclear. Herein, fetal and maternal safety as well as
      the strategy for this unusual surgical procedure during pregnancy in patients
      with UC are considered. A 28-year-old woman was diagnosed with left-sided
      moderate UC at 12 weeks of pregnancy; toxic megacolon was suspected, and surgery
      was required. Although the baby's gestational age was 23 weeks and 3 days, a
      cesarean section was performed before the colectomy. In a next case, a 28-year
      old woman had a 2-year history of left-sided UC. Her colitis flared up at 11
      weeks of pregnancy. Colectomy was performed because her colitis was unresponsive
      to conservative therapy, and the pregnancy was continued, with a transvaginal
      delivery at 36 weeks. In patients with UC, the need for surgery should be
      determined promptly based on disease severity, whether or not the patient is
      pregnant. The need for surgery should not be affected by pregnancy. The pregnancy
      should be continued for as long as possible when there are no fetal and maternal
      complications. Both cesarean section and colectomy should be performed
      independently if necessary. 

PMID- 25960729
TI  - Pericardial biopsy revealed gastric signet-ring cell cancer.
AB  - We describe the case of an 85-year-old man who presented with a large pericardial
      effusion. The patient was admitted because of anorexia and general malaise. Chest
      X-ray revealed an increased cardiothoracic ratio and a small amount of bilateral
      pleural effusion. Two-dimensional ultrasonographic echocardiography showed
      pericardial effusions with atrial and right ventricular early diastolic collapse,
      establishing the diagnosis of cardiac tamponade. Signet-ring cell cancer with
      pericardial involvement was diagnosed by subxiphoid pericardiostomy. The clear
      fluid was removed through pericardial drainage. The signet-ring cell carcinoma of
      the stomach was revealed by gastric fiberscope examination after pericardial
      biopsy proved malignancy. Virchow lymph node metastasis was also found. We
      diagnosed the patient with gastric cancer stage IV and suggested him the best
      supportive therapy. He died of cardiac arrest 1 month after best supportive care.

PMID- 25960730
TI  - A case of swyer syndrome associated with advanced gonadal dysgerminoma involving
      long survival.
AB  - Swyer syndrome is caused by abnormal sex differentiation during the embryonic
      period, resulting in incomplete intrauterine masculinization and undifferentiated
      gonads. The current case report describes a patient with Swyer syndrome
      associated with stage 3 gonadal dysgerminoma who has survived for 23 years. At
      age 18, this patient sought assistance for primary amenorrhea from the
      Gynecological Services Department of the University of Brasilia Hospital. A
      physical examination revealed that the patient was at Tanner stage 4 with respect
      to axillary hair, breasts, and pubic hair; she presented with a eutrophic vagina
      and a small cervix. She was treated with a combination of estrogens and
      progestogens to induce cycling. Approximately 4 years later, a complex tumor was
      found and resected; a histopathological analysis revealed that this tumor was a
      right adnexal dysgerminoma with peritoneal affection. The patient was also
      subjected to chemotherapy. Her follow-up has continued to the present time, with
      no signs of tumor recurrence. In conclusion, this report describes an extremely
      rare case in which Swyer syndrome was associated with ovarian dysgerminoma;
      relative to similar patients, the described patient has survived for an unusually
      prolonged time. 

PMID- 25960731
TI  - Diagnostic Dilemma in Primary Blastomyces dermatitidis Meningitis: Role of
      Neurosurgical Biopsy.
AB  - A 52-year-old male on chronic prednisone for polymyalgia rheumatica presented
      with a subacute history of headaches, nausea, phonophobia, intermittent diplopia
      and gait instability. He was hospitalized 2 weeks prior to presentation with
      extensive evaluations only notable for leptomeningeal inflammation on MRI. His
      symptoms progressively worsened and he developed aphasia. He was transferred to
      our facility where extensive spinal fluid examinations were repeated and were
      again nondiagnostic. Ultimately, a diagnostic skull-based biopsy was performed
      which demonstrated Blastomyces dermatitidis fungal meningitis. Despite extensive
      sampling and cultures, only 1 of the intraoperative samples yielded diagnostic
      results. This underscores the low sensitivity of current methods to diagnose CNS
      blastomycosis. This case suggests that a neurosurgical biopsy may be necessary
      and should be considered early in the diagnostic process, especially if a
      definitive diagnosis is elusive. If a biopsy is performed, sampling should be
      ample and from multiple areas. Following the diagnosis, our patient was treated
      with liposomal amphotericin B and then voriconazole with a good clinical
      response. 

PMID- 25960732
TI  - Irreversible Loss of Vision in a Child due to Occipital Infarction after
      Gastroenteritis.
AB  - A 21/2-year-old girl developed a bilateral occipital infarct following severe
      gastroenteritis with bilateral vision of light perception. Evaluations for sickle
      cell anemia, hemolytic anemia and coagulopathies were negative. Cortical
      blindness is an uncommon but dramatic complication of gastroenteritis, hence the
      need of prompt hydration and other supportive measures to avoid irreversible
      visual loss or mental sequela. 

PMID- 25960733
TI  - Two cases of acute abdomen after an intravitreal injection of bevacizumab.
AB  - We report on a patient with ischemic colitis and another with paralytic ileus,
      both of whom experienced an acute abdomen after intravitreal injection of
      bevacizumab (IVB). Case 1 was a 78-year-old woman. Her medical history included
      surgery for colon carcinoma 10 years earlier. The patient developed acute severe
      abdominal pain and nausea the day after IVB for retinal vein occlusion with
      macular edema, and massive lower gastrointestinal bleeding occurred. Ischemic
      colitis was diagnosed. Case 2 was a 64-year-old man who presented with
      neovascular glaucoma with proliferative diabetic retinopathy. We performed
      vitreous surgery on the 9th day after IVB, and we reperformed IVB at the end of
      the vitreous surgery. On the first postoperative day, severe abdominal
      distension, vomiting and abdominal pain were observed, and paralytic ileus was
      diagnosed. It is possible that gastrointestinal disorders are induced after IVB,
      depending on the patient's background, including for example severe diabetes or a
      history of surgery for gastrointestinal cancer. Thus, ophthalmologists should
      apply alternative therapies instead of IVB to patients with severe diabetes
      mellitus or a history of gastrointestinal cancer. 

PMID- 25960734
TI  - Case report of sump syndrome after laser conjunctivodacryocystorhinostomy.
AB  - The sump syndrome was initially described in relation to patients who had
      undergone external dacryocystorhinostomy. Here we report a case of sump syndrome
      that developed following laser conjunctivodacryocystorhinostomy (CDCR) due to
      tube displacement after a bout of forceful sneezing. Unlike cases of external
      dacryocystorhinostomy where flaps are sutured, there is a potential space created
      by the sac remnants in laser CDCR. Hence, any displacement of the tube will lead
      to the improper drainage of secretions with superadded infections of the contents
      (as occurred in this case). Therefore, in laser CDCR, it is imperative to create
      an appropriately placed osteotomy with a correctly sized tube that is well
      secured to avoid displacement along with patient education regarding tube care. 

PMID- 25960735
TI  - Stroke-Like Presentation of Cerebral Toxoplasmosis: Two HIV-Infected Cases.
AB  - Toxoplasmosis is the most common opportunistic infection of the central nervous
      system in patients with acquired immunodeficiency syndrome (AIDS). Clinical
      presentation of cerebral toxoplasmosis in these patients includes headache, focal
      neurological deficits and seizures. Prompt diagnosis and appropriate therapy
      results in rapid clinical and radiological improvement as well as good outcome
      for patients. In this article, we report two cases with stroke-like presentation
      of cerebral toxoplasmosis in the setting of HIV infection. 

PMID- 25960736
TI  - On the Relationship between Variational Level Set-Based and SOM-Based Active
      Contours.
AB  - Most Active Contour Models (ACMs) deal with the image segmentation problem as a
      functional optimization problem, as they work on dividing an image into several
      regions by optimizing a suitable functional. Among ACMs, variational level set
      methods have been used to build an active contour with the aim of modeling
      arbitrarily complex shapes. Moreover, they can handle also topological changes of
      the contours. Self-Organizing Maps (SOMs) have attracted the attention of many
      computer vision scientists, particularly in modeling an active contour based on
      the idea of utilizing the prototypes (weights) of a SOM to control the evolution
      of the contour. SOM-based models have been proposed in general with the aim of
      exploiting the specific ability of SOMs to learn the edge-map information via
      their topology preservation property and overcoming some drawbacks of other ACMs,
      such as trapping into local minima of the image energy functional to be minimized
      in such models. In this survey, we illustrate the main concepts of variational
      level set-based ACMs, SOM-based ACMs, and their relationship and review in a
      comprehensive fashion the development of their state-of-the-art models from a
      machine learning perspective, with a focus on their strengths and weaknesses. 

PMID- 25960737
TI  - Memory dynamics in attractor networks.
AB  - As can be represented by neurons and their synaptic connections, attractor
      networks are widely believed to underlie biological memory systems and have been
      used extensively in recent years to model the storage and retrieval process of
      memory. In this paper, we propose a new energy function, which is nonnegative and
      attains zero values only at the desired memory patterns. An attractor network is
      designed based on the proposed energy function. It is shown that the desired
      memory patterns are stored as the stable equilibrium points of the attractor
      network. To retrieve a memory pattern, an initial stimulus input is presented to
      the network, and its states converge to one of stable equilibrium points.
      Consequently, the existence of the spurious points, that is, local maxima, saddle
      points, or other local minima which are undesired memory patterns, can be
      avoided. The simulation results show the effectiveness of the proposed method. 

PMID- 25960738
TI  - Fuzzy Controller Design Using Evolutionary Techniques for Twin Rotor MIMO System:
      A Comparative Study.
AB  - This paper presents a comparative study of fuzzy controller design for the twin
      rotor multi-input multioutput (MIMO) system (TRMS) considering most promising
      evolutionary techniques. These are gravitational search algorithm (GSA), particle
      swarm optimization (PSO), artificial bee colony (ABC), and differential evolution
      (DE). In this study, the gains of four fuzzy proportional derivative (PD)
      controllers for TRMS have been optimized using the considered techniques. The
      optimization techniques are developed to identify the optimal control parameters
      for system stability enhancement, to cancel high nonlinearities in the model, to
      reduce the coupling effect, and to drive TRMS pitch and yaw angles into the
      desired tracking trajectory efficiently and accurately. The most effective
      technique in terms of system response due to different disturbances has been
      investigated. In this work, it is observed that GSA is the most effective
      technique in terms of solution quality and convergence speed. 

PMID- 25960739
TI  - Robust adaptive principal component analysis based on intergraph matrix for
      medical image registration.
AB  - This paper proposes a novel robust adaptive principal component analysis (RAPCA)
      method based on intergraph matrix for image registration in order to improve
      robustness and real-time performance. The contributions can be divided into three
      parts. Firstly, a novel RAPCA method is developed to capture the common structure
      patterns based on intergraph matrix of the objects. Secondly, the robust
      similarity measure is proposed based on adaptive principal component. Finally,
      the robust registration algorithm is derived based on the RAPCA. The experimental
      results show that the proposed method is very effective in capturing the common
      structure patterns for image registration on real-world images. 

PMID- 25960741
TI  - MicroRNAs in Pancreatic Cancer: Involvement in Carcinogenesis and Potential Use
      for Diagnosis and Prognosis.
AB  - Pancreatic cancer is one of the most fatal malignancies with increasing incidence
      and high mortality. Possibilities for early diagnosis are limited and there is
      currently no efficient therapy. Molecular markers that have been introduced into
      diagnosis and treatment of other solid tumors remain unreciprocated in this
      disease. Recent discoveries have shown that certain microRNAs (miRNAs) take part
      in fundamental molecular processes associated with pancreatic cancer initiation
      and progression including cell cycle, DNA repair, apoptosis, invasivity, and
      metastasis. The mechanism involves both positive and negative regulation of
      expression of protooncogenes and tumor suppressor genes. Various miRNAs are
      expressed at different levels among normal pancreatic tissue, chronic
      pancreatitis, and pancreatic cancer and may therefore serve as a tool to
      differentiate chronic pancreatitis from early stages of cancer. Other miRNAs can
      indicate the probable course of the disease or determine the survival prognosis.
      In addition, there is a growing interest directed at the understanding of miRNA
      induced molecular mechanisms. The possibility of intervention in the molecular
      mechanisms of miRNAs regulation could begin a new generation of pancreatic cancer
      therapies. This review summarizes the recent reports describing functions of
      miRNAs in cellular processes underlying pancreatic cancerogenesis and their
      utility in diagnosis, survival prognosis, and therapy. 

PMID- 25960742
TI  - The natural history and predictors for intervention in patients with small renal
      mass undergoing active surveillance.
AB  - Aim. To describe the natural history of small renal mass on active surveillance
      and identify parameters that could help in predicting the need for intervention
      in patients with small renal masses undergoing active surveillance. We also
      discuss the need for renal biopsy in the management of these patients. Methods. A
      retrospective analysis of 78 renal masses <=4 cm diagnosed at our Urology
      Department at Bnai Zion Medical Center between September 2003 and March 2012.
      Results. Seventy patients with 78 small renal masses were analyzed. The mean age
      at diagnosis was 68 years (47-89). The mean follow-up period was 34 months (12
      112). In 54 of 78 masses there was a growth of at least 2 mm between imaging on
      last available follow-up and diagnosis. Eight of the 54 (15%) masses which grew
      in size underwent a nephron-sparing surgery, of which two were oncocytomas and
      six were renal cell carcinoma. Growth rate and mass diameter on diagnosis were
      significantly greater in the group of patients who underwent a surgery.
      Conclusions. Small renal masses might eventually be managed by active
      surveillance without compromising survival or surgical approach. All masses that
      were eventually excised underwent a nephron-sparing surgery. None of the patients
      developed metastases. 

PMID- 25960740
TI  - Peripheral signals mediate the beneficial effects of gastric surgery in obesity.
AB  - Obesity is nowadays a public health problem both in the industrialized world and
      developing countries. The different treatments to fight against obesity are not
      very successful with the exception of gastric surgery. The mechanism behind the
      achievement of this procedure remains unclear although the modifications in the
      pattern of gastrointestinal hormones production appear to be responsible for the
      beneficial effect. The gastrointestinal tract has emerged in the last time as an
      endocrine organ in charge of response to the different stimulus related to
      nutritional status by the modulation of more than 30 signals acting at central
      level to modulate food intake and body weight. The production of some of these
      gastric derived signals has been proved to be altered in obesity (ghrelin, CCK,
      and GLP-1). In fact, bariatric surgery modifies the production of both
      gastrointestinal and adipose tissue peripheral signals beyond the gut microbiota
      composition. Through this paper the main peripheral signals altered in obesity
      will be reviewed together with their modifications after bariatric surgery. 

PMID- 25960744
TI  - Long-Lasting Cranial Nerve III Palsy as a Presenting Feature of Chronic
      Inflammatory Demyelinating Polyneuropathy.
AB  - We describe a patient with chronic inflammatory demyelinating polyneuropathy
      (CIDP) in which an adduction deficit and ptosis in the left eye presented several
      years before the polyneuropathy. A 52-year-old man presented with a 14-year
      history of unremitting diplopia, adduction deficit, and ptosis in the left eye.
      At the age of 45 a mild bilateral foot drop and impaired sensation in the four
      limbs appeared, with these symptoms showing a progressive course. The diagnostic
      workup included EMG/ENG which demonstrated reduced conduction velocity with
      bilateral and symmetrical sensory and motor involvement. Cerebrospinal fluid
      studies revealed a cytoalbuminologic dissociation. A prolonged treatment with
      corticosteroids allowed a significant improvement of the limb weakness. Diplopia
      and ptosis remained unchanged. This unusual form of CIDP presented as a long
      lasting isolated cranial nerve palsy. A diagnostic workup for CIDP should
      therefore be performed in those patients in which an isolated and unremitting
      cranial nerve palsy cannot be explained by common causes. 

PMID- 25960745
TI  - A review of on-site wastewater treatment systems in Western Australia from 1997
      to 2011.
AB  - On-site wastewater treatment systems (OWTS) are widely used in Western Australia
      (WA) to treat and dispose of household wastewater in areas where centralized
      sewerage systems are unavailable. Septic tanks, aerobic treatment units (ATUs),
      and composting toilets with greywater systems are among the most well established
      and commonly used OWTS. However, there are concerns that some OWTS installed in
      WA are either performing below expected standards or failing. Poorly performing
      OWTS are often attributed to inadequate installation, inadequate maintenance,
      poor public awareness, insufficient local authority resources, ongoing wastewater
      management issues, or inadequate adoption of standards, procedures, and
      guidelines. This paper is to review the installations and failures of OWTS in WA.
      Recommendations to the Department of Health Western Australia (DOHWA) and Local
      Government (LG) in regard to management strategies and institutional arrangements
      of OWTS are also highlighted. 

PMID- 25960746
TI  - Agaricoglycerides Protect against Hepatic Ischemia/Reperfusion Injury by
      Attenuating Inflammatory Response, Oxidative Stress, and Expression of NF-kappaB.
AB  - We have investigated the effects of agaricoglycerides (AG) in a mouse model of
      hepatic I/R injury. I/R triggered increases/changes in markers of liver injury,
      hepatic oxidative stress, tumor necrosis factor-alpha (TNF-alpha), interleukin
      1beta (IL-1beta), and nuclear factor kappaB (NF-kappaB). AG significantly reduced
      the extent of liver inflammation and oxidative stress and also attenuated the NF
      kappaB activation as well as TNF-alpha and IL-1beta production. Our results
      indicate that AG may represent a novel protective strategy against I/R-induced
      injury and inflammatory diseases. 

PMID- 25960743
TI  - Antifibrotic activity of acylated and unacylated ghrelin.
AB  - Fibrosis can affect almost all tissues and organs, it often represents the
      terminal stage of chronic diseases, and it is regarded as a major health issue
      for which efficient therapies are needed. Tissue injury, by inducing
      necrosis/apoptosis, triggers inflammatory response that, in turn, promotes
      fibroblast activation and pathological deposition of extracellular matrix.
      Acylated and unacylated ghrelin are the main products of the ghrelin gene. The
      acylated form, through its receptor GHSR-1a, stimulates appetite and growth
      hormone (GH) release. Although unacylated ghrelin does not bind or activate GHSR
      1a, it shares with the acylated form several biological activities. Ghrelin
      peptides exhibit anti-inflammatory, antioxidative, and antiapoptotic activities,
      suggesting that they might represent an efficient approach to prevent or reduce
      fibrosis. The aim of this review is to summarize the available evidence regarding
      the effects of acylated and unacylated ghrelin on different pathologies and
      experimental models in which fibrosis is a predominant characteristic. 

PMID- 25960747
TI  - Acupuncture therapy is more effective than artificial tears for dry eye syndrome:
      evidence based on a meta-analysis.
AB  - Background. The efficacy of acupuncture in dry eye syndrome patients remains
      controversial. Methods. Pubmed, Ovid, Cochrane libraries, CNKI, Wanfang, and
      CQVIP databases were electronically searched until October 1, 2014. Outcomes
      including tear break-up time (BUT), Schirmer I test (SIT), and cornea fluorescein
      staining (CFS) were analyzed. A meta-analysis was performed using both fixed- and
      random-effects models based on heterogeneity across studies. Results. Seven
      studies were included in this study; 198 and 185 patients were randomly treated
      with acupuncture and artificial tears, respectively. The overall BUT of patients
      in acupuncture group was significantly longer than that of the artificial tears
      group after treatment (P < 0.00001). The SIT was significantly higher in the
      acupuncture group than that in the artificial tears group after treatment (P =
      0.001). The CFS of patients in acupuncture group was significantly improved
      compared to that in artificial group (P < 0.0001). Conclusions. Acupuncture
      therapy is effective for the dry eye patients, partly better than artificial tear
      treatment. 

PMID- 25960749
TI  - Deqi sensation in different kinds of acupuncture 2014.

PMID- 25960748
TI  - Aqueous Extract of Agaricus blazei Murrill Prevents Age-Related Changes in the
      Myenteric Plexus of the Jejunum in Rats.
AB  - This study evaluated the effects of the supplementation with aqueous extract of
      Agaricus blazei Murrill (ABM) on biometric and blood parameters and quantitative
      morphology of the myenteric plexus and jejunal wall in aging Wistar rats. The
      animals were euthanized at 7 (C7), 12 (C12 and CA12), and 23 months of age (C23
      and CA23). The CA12 and CA23 groups received a daily dose of ABM extract (26
      mg/animal) via gavage, beginning at 7 months of age. A reduction in food intake
      was observed with aging, with increases in the Lee index, retroperitoneal fat,
      intestinal length, and levels of total cholesterol and total proteins. Aging led
      to a reduction of the total wall thickness, mucosa tunic, villus height, crypt
      depth, and number of goblet cells. In the myenteric plexus, aging quantitatively
      decreased the population of HuC/D(+) neuronal and S100(+) glial cells, with
      maintenance of the nNOS(+) nitrergic subpopulation and increase in the cell body
      area of these populations. Supplementation with the ABM extract preserved the
      myenteric plexus in old animals, in which no differences were detected in the
      density and cell body profile of neurons and glial cells in the CA12 and CA23
      groups, compared with C7 group. The supplementation with the aqueous extract of
      ABM efficiently maintained myenteric plexus homeostasis, which positively
      influenced the physiology and prevented the death of the neurons and glial cells.

PMID- 25960750
TI  - Farnesol, a sesquiterpene alcohol in herbal plants, exerts anti-inflammatory and
      antiallergic effects on ovalbumin-sensitized and -challenged asthmatic mice.
AB  - To investigate the effect of farnesol on allergic asthma, three farnesol doses
      were extra-added into AIN-76 feed consumed by ovalbumin- (OVA-) sensitized and 
      challenged mice continuously for 5 weeks, at approximately 5, 25, and 100 mg
      farnesol/kg, BW/day. The results showed that there were no significant
      differences in body weight, feed intake, and visceral organ weights between the
      farnesol supplementation and dietary control groups. Farnesol supplementation
      decreased interleukin (IL)-6/IL-10 level ratios in bronchoalveolar lavage fluid
      (BALF). Farnesol supplementation significantly (P < 0.05) restored the cytokine
      secretion ability of peritoneal macrophages that was suppressed as a result of
      OVA sensitization and challenge and slightly decreased tumor necrosis factor (TNF
      alpha)/IL-10 cytokine secretion ratios. Farnesol supplementation slightly (P >
      0.05) decreased IL-4 but significantly (P < 0.05) increased IL-2 levels secreted
      by the splenocytes in the presence of OVA, implying that farnesol might have a
      systemic antiallergic effect on allergic asthmatic mice. Farnesol supplementation
      significantly (P < 0.05) increased IL-10 levels secreted by the splenocytes in
      the presence of OVA, suggesting that farnesol might have an anti-inflammatory
      potential to allergic asthmatic mice. Overall, our results suggest that farnesol
      supplementation may be beneficial to improve the Th2-skewed allergic asthmatic
      inflammation. 

PMID- 25960751
TI  - Protective Effect of Hericium erinaceus on Alcohol Induced Hepatotoxicity in
      Mice.
AB  - We investigated the effects of Hericium erinaceus (HEM) on liver injury induced
      by acute alcohol administration in mice. Mice received ethanol (5 g/kg BW) by
      gavage every 12 hrs for a total of 3 doses. HEM (200 mg/kg BW) was gavage before
      ethanol administration. Subsequent serum alanine aminotransferase (ALT) level,
      aspartate aminotransaminase (AST) level, Maleic dialdehyde (MDA) level, hepatic
      total antioxidant status (TAOS), and activated nuclear factor kappa-light-chain
      enhancer of activated B cells (NF-kappaB) were determined by ELISA and
      immunohistochemistry, respectively. HEM administration markedly (P < 0.05)
      decreased serum ALT, AST, and MDA levels. The hepatic histopathological
      observations showed that HEM had a relatively significant role in mice model,
      which had alcoholic liver damage. In conclusion, we observed that HEM (200 mg/kg
      BW) supplementation could restrain the hepatic damage caused by acute alcohol
      exposure. 

PMID- 25960752
TI  - Chemical composition and disruption of quorum sensing signaling in geographically
      diverse United States propolis.
AB  - Propolis or bee glue has been used for centuries for various purposes and is
      especially important in human health due to many of its biological and
      pharmacological properties. In this work we showed quorum sensing inhibitory
      (QSI) activity of ten geographically distinct propolis samples from the United
      States using the acyl-homoserine lactone- (AHL-) dependent Chromobacterium
      violaceum strain CV026. Based on GC-MS chemical profiling the propolis samples
      can be classified into several groups that are as follows: (1) rich in cinnamic
      acid derivatives, (2) rich in flavonoids, and (3) rich in triterpenes. An in
      depth analysis of the propolis from North Carolina led to the isolation and
      identification of a triterpenic acid that was recently isolated from Hondurian
      propolis (Central America) and ethyl ether of p-coumaric alcohol not previously
      identified in bee propolis. QSI activity was also observed in the second group US
      propolis samples which contained the flavonoid pinocembrin in addition to other
      flavonoid compounds. The discovery of compounds that are involved in QSI activity
      has the potential to facilitate studies that may lead to the development of
      antivirulence therapies that can be complementary and/or alternative treatments
      against antibiotic resistant bacterial pathogens and/or emerging pathogens that
      have yet to be identified. 

PMID- 25960753
TI  - The Chemical Constituents and Pharmacological Actions of Cordyceps sinensis.
AB  - Cordyceps sinensis, also called DongChongXiaCao (winter worm, summer grass) in
      Chinese, is becoming increasingly popular and important in the public and
      scientific communities. This study summarizes the chemical constituents and their
      corresponding pharmacological actions of Cordyceps sinensis. Many bioactive
      components of Cordyceps sinensis have been extracted including nucleoside,
      polysaccharide, sterol, protein, amino acid, and polypeptide. In addition, these
      constituents' corresponding pharmacological actions were also shown in the study
      such as anti-inflammatory, antioxidant, antitumour, antiapoptosis, and
      immunomodulatory actions. Therefore can use different effects of C. sinensis
      against different diseases and provide reference for the study of Cordyceps
      sinensis in the future. 

PMID- 25960754
TI  - Protective Effect of Ethanol Extracts of Hericium erinaceus on Alloxan-Induced
      Diabetic Neuropathic Pain in Rats.
AB  - We investigated the effects of Hericium erinaceus (HEE) on alloxan induced
      diabetic neuropathic pain in laboratory rats. Alloxan induced diabetic rats were
      administered orally HEE. After 6 weeks of treatments, treatment with HEE 40 mg/kg
      in diabetic animals showed significant increase in pain threshold and paw
      withdrawal threshold and significant decrease in serum glucose and urine glucose.
      We also observed a significant increase in lactate dehydrogenase (LDH), Lipid
      peroxidation (LPO), glutathione peroxidase (GPx) activity, glutathione reductase
      (GR) activity, catalase (CAT) activity, Na(+)K(+)ATPase activity, and glutathione
      S transferase (GST) activity along with significant decreased levels of
      glutathione (GSH) content in diabetic rats. The total antioxidant status (TAOS)
      in the HEE-treated groups was significantly lower than that in the alloxan
      treated group. HEE can offer pain relief in diabetic neuropathic pain. The
      improvement in diabetic state after HEE treatment along with the antioxidant
      activity could be the probable way by which it had alleviated diabetic
      neuropathy. 

PMID- 25960755
TI  - A survey of the practice and perspectives of chinese acupuncturists on deqi.
AB  - Deqi refers to the special sensation and reaction sensed mainly by both
      acupuncturist and patient when a needle was inserted into the acupoints and is
      considered to be vital to achieve acupuncture effect. For acupuncturist, it is
      important to judge and control Deqi in clinical practice. However, enough
      attention is paid to patients' feelings rather than acupuncturists' nowadays. We
      thus conducted this survey to determine acupuncturists' perspectives about Deqi
      and to further find the proper way to induce Deqi. A total of 250 questionnaires
      were sent out to acupuncturists and 202 (80.8%) were returned. According to the
      results, most acupuncturists believe that Deqi is vital to obtain preferable
      clinical effects. The reliability of acupuncturists' Deqi sensation ranks as
      sinking> tightening> astringent. The reliability of patients' Deqi sensations
      ranks as sourness> numbness> distention> heaviness> pain. The reliability of
      influential factors ranks as manipulation> specificity of acupoint> TCM
      constitution> disease status> patient's psychological condition> acupuncturists'
      psychological guidance> clinical environment. This study is believed to provide
      additional evidence to the qualitative and quantitative research of Deqi in the
      future. 

PMID- 25960756
TI  - Vasorelaxant and Hypotensive Effects of Jaboticaba Fruit (Myrciaria cauliflora)
      Extract in Rats.
AB  - This study's aim was to determine the effect of hydroalcoholic extract of M.
      cauliflora (HEMC) on vascular tension and blood pressure in rats. In our in vitro
      studies using precontracted isolated aortas from rats, HEMC and acetylcholine
      (positive control) induced relaxation only in vessels with endothelium.
      Pretreatment with L-NAME (NO synthase inhibitor) or ODQ (soluble guanylyl cyclase
      (sGC) inhibitor) abolished the HEMC-induced relaxation. The treatment with MDL
      12,330A (adenylyl cyclase (AC) inhibitor) or diclofenac (COX inhibitor) reduced
      HEMC-induced vasorelaxation. The blockade of muscarinic and beta-adrenergic
      receptors (by atropine and propranolol, resp.) did not promote changes in HEMC
      induced vasorelaxation. In our in vivo studies, catheters were inserted into the
      right femoral vein and artery of anesthetized rats for HEMC infusion and the
      measurement of blood pressure, heart rate, and aortic blood flow. The intravenous
      infusion of HEMC produced hypotension and increased aortic blood flow with no
      changes in heart rate. These findings showed that HEMC induces endothelium
      dependent vascular relaxation and hypotension with no alteration in heart rate.
      The NO/sGC/cGMP pathway seems to be the main cellular route involved in the
      vascular responsiveness. 

PMID- 25960758
TI  - Medicinal mushroom for prevention of disease of modern civilization.

PMID- 25960757
TI  - Triterpenoids and Polysaccharide Fractions of Ganoderma tsugae Exert Different
      Effects on Antiallergic Activities.
AB  - This study was to investigate antiallergic effects of triterpenoids (Gt-TRE) and
      polysaccharide (Gt-PS) extracts from Ganoderma tsugae, using mast cell line RBL
      2H3, T cell line EL4, primary T cells, and transfected RAW264.7 macrophage cells.
      The results showed that histamine secreted from activated RBL-2H3 mast cells was
      significantly suppressed by Gt-TRE but not Gt-PS. Interleukin- (IL-) 4 secreted
      from activated EL4 cells was significantly suppressed by Gt-TRE but not Gt-PS.
      Further primary CD4(+) T cells cultures also confirmed that Gt-TRE (5 ~ 50 ug/mL)
      significantly suppressed Th2 cytokines IL-4 and IL-5 secretions but had no effect
      on Th1 cytokines IL-2 and interferon (IFN)-gamma. Gt-PS did not affect IL-4 and
      IL-5 secretions until higher doses (400, 500 ug/mL) and significantly suppressed
      IFNgamma secretions but enhanced IL-2 at these high doses. The reporter gene
      assay indicated that Gt-TRE inhibited but Gt-PS enhanced the transcriptional
      activity of NF-kappaB in activated transfected RAW264.7 cells and transfected EL4
      cells. IL-4 secreted by this transfected EL-4 cells was also significantly
      decreased by Gt-TRE but not by Gt-PS, suggesting that these two fractions may
      exert different effects on NF-kappaB related cytokines expression. These data
      suggested that triterpenoids fraction of Ganoderma tsugae might be the main
      constituents to alleviate allergic asthma. 

PMID- 25960759
TI  - Chemical Constituents and Evaluation of Antimicrobial and Cytotoxic Activities of
      Kielmeyera coriacea Mart. & Zucc. Essential Oils.
AB  - Many essential oils (EOs) of different plant species possess interesting
      antimicrobial effects on buccal microorganisms and cytotoxic properties. EOs of
      Kielmeyera coriacea Mart. & Zucc. were analyzed by gas chromatography coupled to
      mass spectrometry (GC-MS). The EO from leaves is rich in sesquiterpenes
      hydrocarbons and oxygenated sesquiterpenes. The three major compounds identified
      were germacrene-D (24.2%), (E)-caryophyllene (15.5%), and bicyclogermacrene
      (11.6%). The inner bark EO is composed mainly of sesquiterpenes hydrocarbons and
      the major components are alpha-copaene (14.9%) and alpha-(E)-bergamotene (13.0%).
      The outer bark EO is composed mainly of oxygenated sesquiterpenes and long-chain
      alkanes, and the major components are alpha-eudesmol (4.2%) and nonacosane
      (5.8%). The wood EO is mainly composed of long-chain alkanes and fatty acids, and
      the major components are nonacosane (9.7%) and palmitic acid (16.2%). The inner
      bark EO showed the strongest antimicrobial activity against the anaerobic
      bacteria Prevotella nigrescens (minimum inhibitory concentration-MIC of 50 ug mL(
      1)). The outer bark and wood EOs showed MICs of 100 ug mL(-1) for all aerobic
      microorganisms tested. The EOs presented low toxicity to Vero cells. These
      results suggest that K. coriacea, a Brazilian plant, provide initial evidence of
      a new and alternative source of substances with medicinal interest. 

PMID- 25960760
TI  - Factors related to NT-proBNP levels in HIV patients aged over 40 years.
AB  - OBJECTIVE: To determine the levels of NT-pro BNP in HIV patients over 40 years
      who are receiving highly active antiretroviral therapy (HAART) and investigating
      potential independent clinical or laboratory factors. METHOD: We determine levels
      of NT-pro BNP in peripheral blood of HIV patients from Costa del Sol Hospital,
      over 40 years. We collected epidemiological, classical cardiovascular risk
      factors and variables associated with HIV infection status. The qualitative
      variables were compared using the chi2 test. NT-proBNP levels were taken as the
      dependent variable. The association between these levels and the quantitative
      variables were studied by analysis of variance (ANOVA), and the association with
      the qualitative variables, using Student's t test. RESULTS: Nt-pro BNP levels
      were determined in 146 HIV patients. We assess the 10-year cardiovascular risk
      calculated by the Framingham equation, 59 (41.5%) were classified as low risk, 46
      (32.4%) as a moderate risk and 37 (26.1%) as a high risk. The higher levels of NT
      pro BNP were found in women, and in those patient with lower filtration rate and
      high levels of triglycerides. An association was also observed between higher
      levels of NT-proBNP and the recent use of lamivudine and fosamprenavir. After a
      multivariate analysis we found an association between higher levels of NT-proBNP
      and the current use of fosamprenavir and a lower glomerular filtration rate.
      CONCLUSIONS: We found, with the limitations of a small serie, that higher levels
      of NTproBNP in HIV patients could be linked to the occurrence of cardiovascular
      events, this fact suggest that NTpro BNP could be used in patients at moderate or
      high vascular risk in order to optimise the primary prevention of vascular
      events.

PMID- 25960761
TI  - Fine taxonomic sampling of nervous systems within Naididae (Annelida: Clitellata)
      reveals evolutionary lability and revised homologies of annelid neural
      components.
AB  - INTRODUCTION: An important goal for understanding how animals have evolved is to
      reconstruct the ancestral features and evolution of the nervous system. Many
      inferences about nervous system evolution are weak because of sparse taxonomic
      sampling and deep phylogenetic distances among species compared. Increasing
      sampling within clades can strengthen inferences by revealing which features are
      conserved and which are variable within them. Among the Annelida, the segmented
      worms, the Clitellata are typically considered as having a largely conserved
      neural architecture, though this view is based on limited sampling. RESULTS: To
      gain better understanding of nervous system evolution within Clitellata, we used
      immunohistochemistry and confocal laser scanning microscopy to describe the
      nervous system architecture of 12 species of the basally branching family
      Naididae. Although we found considerable similarity in the nervous system
      architecture of naidids and that of other clitellate groups, our study identified
      a number of features that are variable within this family, including some that
      are variable even among relatively closely related species. Variable features
      include the position of the brain, the number of ciliary sense organs, the
      presence of septate ventral nerve cord ganglia, the distribution of serotonergic
      cells in the brain and ventral ganglia, and the number of peripheral segmental
      nerves. CONCLUSIONS: Our analysis of patterns of serotonin immunoreactive
      perikarya in the central nervous system indicates that segmental units are not
      structurally homogeneous, and preliminary homology assessments suggest that whole
      sets of serotonin immunoreactive cells have been gained and lost across the
      Clitellata. We also found that the relative position of neuroectodermal and
      mesodermal segmental components is surprisingly evolutionarily labile; in turn,
      this revealed that scoring segmental nerves by their position relative to
      segmental ganglia rather than to segmental septa clarifies their homologies
      across Annelida. We conclude that fine taxonomic sampling in comparative studies
      aimed at elucidating the evolution of morphological diversity is fundamental for
      proper assessment of trait variability.

PMID- 25960764
TI  - Effect of fluid friction on interstitial fluid flow coupled with blood flow
      through solid tumor microvascular network.
AB  - A solid tumor is investigated as porous media for fluid flow simulation. Most of
      the studies use Darcy model for porous media. In Darcy model, the fluid friction
      is neglected and a few simplified assumptions are implemented. In this study, the
      effect of these assumptions is studied by considering Brinkman model. A
      multiscale mathematical method which calculates fluid flow to a solid tumor is
      used in this study to investigate how neglecting fluid friction affects the solid
      tumor simulation. The mathematical method involves processes such as blood flow
      through vessels and solute and fluid diffusion, convective transport in
      extracellular matrix, and extravasation from blood vessels. The sprouting
      angiogenesis model is used for generating capillary network and then fluid flow
      governing equations are implemented to calculate blood flow through the tumor
      induced capillary network. Finally, the two models of porous media are used for
      modeling fluid flow in normal and tumor tissues in three different shapes of
      tumors. Simulations of interstitial fluid transport in a solid tumor demonstrate
      that the simplifications used in Darcy model affect the interstitial velocity and
      Brinkman model predicts a lower value for interstitial velocity than the values
      that Darcy model predicts. 

PMID- 25960763
TI  - Existential security is a necessary condition for continued breastfeeding despite
      severe initial difficulties: a lifeworld hermeneutical study.
AB  - BACKGROUND: The majority of new mothers in Sweden initiate breastfeeding and many
      experience initial difficulties. This experience is an important cause of early
      breastfeeding cessation. To increase understanding, there is a need to explore
      the lived experiences of the decision to continue or cease breastfeeding. The aim
      of this study is therefore to explain and understand how this decision is
      influenced by the meaning of severe initial difficulties. METHODS: A lifeworld
      hermeneutical approach was used for the study. The study was conducted in Sweden
      with eight mothers who experienced severe difficulties with initial
      breastfeeding. All except one were interviewed on two different occasions
      resulting in fifteen interviews. The interviews were conducted between 2010 and
      2013. RESULTS: Mothers who experience severe difficulties with initial
      breastfeeding feel both overtaken and violated not only by their own infants and
      their own bodies but also by their anger, expectations, loneliness and care from
      health professionals. These feelings of being overtaken and invaded provoke an
      existential crisis and place mothers at a turning point in which these feelings
      are compared and put in relation to one another in the negotiation of the
      decision to continue or cease breastfeeding. This decision thus depends on the
      possibility of feeling secure with the breastfeeding relationship. If insecurity
      dominates, this can, in severe cases, create a feeling of fear of breastfeeding
      that is so great that there is no alternative but to stop breastfeeding.
      CONCLUSIONS: Existential security in the breastfeeding relationship seems to be
      an underlying factor for confidence and therefore a necessary condition for
      continued breastfeeding when having severe initial breastfeeding difficulties.
      Unresolved feelings of insecurity may be a serious barrier to further
      breastfeeding that can result in a fear of breastfeeding. Such fear can force the
      mother to cease breastfeeding. This study highlights how women are situated in a
      complex cultural and biological context of breastfeeding that has existential
      consequences for them. An existential crisis forces mothers into a turning point
      for the breastfeeding decision. In the existential crisis, mothers'
      responsibility for the mother-infant relationship guides continuing or ceasing
      breastfeeding.

PMID- 25960765
TI  - Comparison between remote sensing and a dynamic vegetation model for estimating
      terrestrial primary production of Africa.
AB  - BACKGROUND: Africa is an important part of the global carbon cycle. It is also a
      continent facing potential problems due to increasing resource demand in
      combination with climate change-induced changes in resource supply. Quantifying
      the pools and fluxes constituting the terrestrial African carbon cycle is a
      challenge, because of uncertainties in meteorological driver data, lack of
      validation data, and potentially uncertain representation of important processes
      in major ecosystems. In this paper, terrestrial primary production estimates
      derived from remote sensing and a dynamic vegetation model are compared and
      quantified for major African land cover types. RESULTS: Continental gross primary
      production estimates derived from remote sensing were higher than corresponding
      estimates derived from a dynamic vegetation model. However, estimates of
      continental net primary production from remote sensing were lower than
      corresponding estimates from the dynamic vegetation model. Variation was found
      among land cover classes, and the largest differences in gross primary production
      were found in the evergreen broadleaf forest. Average carbon use efficiency
      (NPP/GPP) was 0.58 for the vegetation model and 0.46 for the remote sensing
      method. Validation versus in situ data of aboveground net primary production
      revealed significant positive relationships for both methods. A combination of
      the remote sensing method with the dynamic vegetation model did not strongly
      affect this relationship. CONCLUSION: Observed significant differences in
      estimated vegetation productivity may have several causes, including model design
      and temperature sensitivity. Differences in carbon use efficiency reflect
      underlying model assumptions. Integrating the realistic process representation of
      dynamic vegetation models with the high resolution observational strength of
      remote sensing may support realistic estimation of components of the carbon cycle
      and enhance resource monitoring, providing suitable validation data is available.

PMID- 25960762
TI  - The missing pieces of the HCV entry puzzle.
AB  - The past decade has witnessed steady and rapid progress in HCV research, which
      has led to the recent breakthrough in therapies against this significant human
      pathogen. Yet a deeper understanding of the life cycle of the virus is required
      to develop more affordable treatments and to advance vaccine design. HCV entry
      presents both a challenge for scientific research and an opportunity for
      alternative intervention approaches, owning to its highly complex nature and the
      myriad of players involved. More than half a dozen cellular proteins are
      implicated in HCV entry; and a more definitive picture regarding the structures
      of the glycoproteins is emerging. A role of apolipoproteins in HCV entry has also
      been established. Still, major questions remain, and the answers to these, which
      we summarize in this review, will hopefully close the gaps in our understanding
      and complete the puzzle that is HCV entry.

PMID- 25960766
TI  - Brief report: large individual variation in outcomes of autistic children
      receiving low-intensity behavioral interventions in community settings.
AB  - BACKGROUND: Despite widespread awareness of the necessity of early intervention
      for children with autism spectrum disorders (ASDs), evidence is still limited, in
      part, due to the complex nature of ASDs. This exploratory study aimed to examine
      the change across time in young children with autism and their mothers, who
      received less intensive early interventions with and without applied behavior
      analysis (ABA) methods in community settings in Japan. METHODS: Eighteen children
      with autism (mean age: 45.7 months; range: 28-64 months) received ABA-based
      treatment (a median of 3.5 hours per week; an interquartile range of 2-5.6 hours
      per week) and/or eclectic treatment-as-usual (TAU) (a median of 3.1 hours per
      week; an interquartile range of 2-5.6 hours per week). Children's outcomes were
      the severity of autistic symptoms, cognitive functioning, internalizing and
      externalizing behavior after 6 months (a median of 192 days; an interquartile
      range of 178-206 days). In addition, maternal parenting stress at 6-month follow
      up, and maternal depression at 1.5-year follow-up (a median of 512 days; an
      interquartile range of 358-545 days) were also examined. RESULTS: Large
      individual variations were observed for a broad range of children's and mothers'
      outcomes. Neither ABA nor TAU hours per week were significantly associated with
      an improvement in core autistic symptoms. A significant improvement was observed
      only for internalizing problems, irrespective of the type, intensity or monthly
      cost of treatment received. Higher ABA cost per month (a median of 1,188 USD; an
      interquartile range of 538-1,888 USD) was associated with less improvement in
      language-social DQ (a median of 9; an interquartile range of -6.75-23.75).
      CONCLUSIONS: To determine an optimal program for each child with ASD in areas
      with poor ASD resources, further controlled studies are needed that assess a
      broad range of predictive and outcome variables focusing on both individual
      characteristics and treatment components.

PMID- 25960767
TI  - Phaeodactylum tricornutum photorespiration takes part in glycerol metabolism and
      is important for nitrogen-limited response.
AB  - BACKGROUND: Microalgae are potential sources of biofuels and high-value
      compounds. Mixotrophic conditions usually promote growth of microalgae. The
      pennate diatom Phaeodactylum tricornutum, with its short life cycle, completely
      sequenced genome, and ease of transformation, can be used as a model for studying
      carbon metabolism in microalgae. RESULTS: We compared the growth rate of P.
      tricornutum (IOCAS-001) under different conditions and labeled the cells using
      [(13)C]glycerol (GL). The results revealed GL promoted the growth of P.
      tricornutum. Ser and Gly were synthesized via photorespiration. The (13)C
      enrichment of Ser and Gly under nitrogen-limited conditions was much higher
      compared to other amino acids, indicating the enhancement of photorespiration.
      Addition of sodium acetate decreased the growth rate of P. tricornutum under
      nitrogen-limited conditions. Our results indicated that the GL carbon backbone
      enters the Calvin cycle in the form of dihydroxyacetone phosphate (DHAP),
      producing xylulose 5-phosphate (X5P) with a GL2_3-generated carbon backbone
      distributed at X5P1_2 and ribose 5-phosphate (R5P) with GL1-derived carbon atoms
      at R5P1 and R5P2. Both R5P and X5P can be converted into ribulose-1,5
      bisphosphate (RuBP). By oxygenation of RuBP carboxylase/oxygenase (Rubisco) and
      metabolism through photorespiration, these RuBPs generate Ser and Gly with GL1 or
      GL2-derived carbon atoms at position 1 and GL1 or GL3-derived carbon atoms at
      other positions, resulting in a low level of (13)C enrichment of Gly1 and Ser1.
      CONCLUSION: Our results indicated different strains of P. tricornutum have
      different mechanisms for organic carbon metabolism. Photorespiration is involved
      in GL metabolism and is important for the nitrogen-limited response in P.
      tricornutum. CLASSIFICATION: Metabolic flux analysis, microalgae.

PMID- 25960768
TI  - Pan-cancer stratification of solid human epithelial tumors and cancer cell lines
      reveals commonalities and tissue-specific features of the CpG island methylator
      phenotype.
AB  - BACKGROUND: The term CpG island methylator phenotype (CIMP) has been used to
      describe widespread DNA hypermethylation at CpG-rich genomic regions affecting
      clinically distinct subsets of cancer patients. Even though there have been
      numerous studies of CIMP in individual cancer types, a uniform analysis across
      tissues is still lacking. RESULTS: We analyze genome-wide patterns of CpG island
      hypermethylation in 5,253 solid epithelial tumors from 15 cancer types from TCGA
      and 23 cancer cell lines from ENCODE. We identify differentially methylated loci
      that define CIMP+ and CIMP- samples, and we use unsupervised clustering to
      provide a robust molecular stratification of tumor methylomes for 12 cancer types
      and all cancer cell lines. With a minimal set of 89 discriminative loci, we
      demonstrate accurate pan-cancer separation of the 12 CIMP+/- subpopulations,
      based on their average levels of methylation. Tumor samples in different CIMP
      subclasses show distinctive correlations with gene expression profiles and
      recurrence of somatic mutations, copy number variations, and epigenetic
      silencing. Enrichment analyses indicate shared canonical pathways and upstream
      regulators for CIMP-targeted regions across cancer types. Furthermore, genomic
      alterations showing consistent associations with CIMP+/- status include genes
      involved in DNA repair, chromatin remodeling genes, and several histone
      methyltransferases. Associations of CIMP status with specific clinical features,
      including overall survival in several cancer types, highlight the importance of
      the CIMP+/- designation for individual tumor evaluation and personalized
      medicine. CONCLUSIONS: We present a comprehensive computational study of CIMP
      that reveals pan-cancer commonalities and tissue-specific differences underlying
      concurrent hypermethylation of CpG islands across tumors. Our stratification of
      solid tumors and cancer cell lines based on CIMP status is data-driven and
      agnostic to tumor type by design, which protects against known biases that have
      hindered classic methods previously used to define CIMP. The results that we
      provide can be used to refine existing molecular subtypes of cancer into more
      homogeneously behaving subgroups, potentially leading to more uniform responses
      in clinical trials.

PMID- 25960769
TI  - Cigarette smoking worsens systemic inflammation in persons with metabolic
      syndrome.
AB  - BACKGROUND: Emerging data suggests that the combination of smoking and metabolic
      syndrome (MetS) markedly increases cardiovascular disease risk well beyond that
      of either condition. In this study we assess if this interaction can be explained
      by an additive increase in the risk of systemic inflammation by MetS and
      cigarette smoking. METHODS: We evaluated 5,503 healthy non-diabetic Brazilian
      subjects (mean age of 43 +/- 10 years, 79% males). Participants were divided into
      sub-groups of smokers and non-smokers with or without MetS. High-sensitivity C
      reactive protein (hs-CRP) was measured to assess degree of underlying
      inflammation. RESULTS: Overall (19%) had hs-CRP > 3 mg/L. In adjusted regression
      analyses, compared to non-smokers, there was a 0.19 mg/L (95% CI: 0.05, 0.32)
      increase in hs-CRP among smokers in the entire population and 0.63 mg/L (95% CI:
      0.26, 1.01) increase among smokers with MetS while there was no significant
      increase among smokers without MetS (beta = 0.09 95% CI: -0.05, 0.24). In a fully
      adjusted logistic regression model, smokers compared to non-smokers were 55% more
      likely to have elevated hs-CRP in the entire population (OR 1.55, 95% CI: 1.25,
      1.92) and more than twice as likely to have elevated hs-CRP if they had MetS ( OR
      2.05, 95% CI: 1.40, 3.01) while the risk was non-significant among those without
      MetS (OR = 1.29, 95% CI: 0.98, 1.69). CONCLUSION: The study demonstrates an
      additive effect of cigarette smoking on the risk of systemic inflammation in MetS
      thus highlighting the need for determining smoking status among those with MetS
      and aggressively targeting smoking cessation in this population.

PMID- 25960770
TI  - A potential link between endothelial function, cardiovascular risk, and metabolic
      syndrome in patients with Non-alcoholic fatty liver disease.
AB  - BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous competitive
      inhibitor of nitric oxide (NO) synthetase. Elevated ADMA reduces NO formation and
      is associated with endothelial dysfunction. The aims of this study were to
      evaluate endothelial function and the cardiovascular risk (CVR) profile in
      patients with non-alcoholic fatty liver disease (NAFLD), and to determine whether
      or not an association with metabolic syndrome (MS) increases these parameters.
      METHODS: A total of 100 consecutive patients with NAFLD, who were seen in Liver
      Disease Outpatient clinic and 45 age- and sex-matched controls were included.
      Endothelial function was evaluated based on the serum ADMA level measured using a
      validated ELISA kit (DLD Diagnostika GMBH, Hamburg, Germany) and flow-mediated
      vasodilatation (FMV) measured via high-resolution external ultrasonography. The
      CVR profile was calculated according to the Framingham equation. RESULTS: At
      baseline there weren't any significant differences in brachial artery diameter
      between the NAFLD and control groups (3.7 +/- 0.6 mm vs. 3.6 +/- 0.6 mm,
      respectively). FMV and flow-independent vasodilatation in response to sublingual
      nitroglycerin did not differ between the NAFLD and control groups (mean: 16% +/-
      9.4% vs. 17.9% +/- 12.4%, and 21.4% +/- 14% vs. 17.8% +/- 11.3%, respectively, p
      > 0.05). No significant difference in the serum ADMA concentration between the
      NAFLD and control groups was observed (mean: 0.8 +/- 0.07 MUmol L(-1) vs. 0.74 +/
      0.2 MUmol L(-1), respectively). The CVR profile was significantly higher in the
      NAFLD group than in the control group (mean: 9% +/- 6.9% vs. 4.6% +/- 3.8%, P =
      0.000). MS associated with NAFLD significantly increased the CVR profile (mean:
      11.2% +/- 7.4%, P = 0.000). An abnormal serum alanine aminotransferase level (>37
      IU L(-1)) and the presence of fibrosis did not increase the CVR profile (p >
      0.05). CONCLUSIONS: The risk of cardiovascular events is increased in patients
      with NAFLD. The association with MS is further increased such risk.

PMID- 25960771
TI  - Health literacy skills in type 2 diabetes mellitus outpatients from an university
      affiliated hospital in Rio de Janeiro, Brazil.
AB  - BACKGROUND: Type 2 diabetes mellitus is the most common metabolic disorder and
      has considerable impact on quality of life. Treatment of DM2 is complex and
      adherence to treatment requires sophisticated cognition which includes literacy
      skills. METHODS: Health literacy skills of a cross-sectional nonrandom sample of
      164 DM2 outpatients at the Diabetes Unit of the Hospital Universitario Pedro
      Ernesto at the State University of Rio de Janeiro were evaluated by the short
      version of the Test of Functional Health Literacy in Adults (s-TOFHLA).
      Procedures available in the SPSS package were used in data analysis. RESULTS:
      Fourteen out of 164 patients (8.5%) were completely illiterate and therefore were
      not further assessed. The remaining 150 patients (75 men and 75 women) were the
      participants of this study. Data showed that 110 (73.3%) participants had
      adequate health literacy skills, 17 (11.3%) had marginal skills and 23 (15.3%)
      had inadequate skills. Moreover, older participants performed worse than younger
      patients. In addition, Caucasian and multiethnic participants performed better
      than Afro-Brazilians. Furthermore, participants with higher educational and
      occupational levels outperformed those with lower levels. However, only age and
      education, but not ethnic group and occupation, contributed significantly and
      independently to health literacy. CONCLUSION: This study showed that almost a
      quarter of the participants are illiterate or have inadequate health literacy
      skills. Therefore, our results indicate the need for the development of health
      care instructions properly calibrated to the health literacy skills of DM2
      patients.

PMID- 25960772
TI  - Effects of diet and exercise interventions on diabetes risk factors in adults
      without diabetes: meta-analyses of controlled trials.
AB  - BACKGROUND AND AIMS: Fasting insulin (FI), fasting glucose (FG), systolic blood
      pressure (SBP), high density lipoproteins (HDL), triacylglycerides (TAG), and
      body mass index (BMI) are well-known risk factors for type 2 diabetes. Reliable
      estimates of lifestyle intervention effects on these factors allow diabetes risk
      to be predicted accurately. The present meta-analyses were conducted to
      quantitatively summarize effects of diet and exercise intervention programs on
      FI, FG, SBP, HDL, TAG and BMI in adults without diabetes. MATERIALS AND METHODS:
      MEDLINE and EMBASE were searched to find studies involving diet plus exercise
      interventions. Studies were required to use adults not diagnosed with type 2
      diabetes, involve both dietary and exercise counseling, and include changes in
      diabetes risk factors as outcome measures. Data from 18, 24, 23, 30, 29 and 29
      studies were used for the analyses of FI, FG, SBP, HDL, TAG and BMI,
      respectively. About 60% of the studies included exclusively overweight or obese
      adults. Mean age and BMI of participants at baseline were 48 years and 30.1
      kg/m(2). Heterogeneity of intervention effects was first estimated using random
      effect models and explained further with mixed-effects models. RESULTS: Adults
      receiving diet and exercise education for approximately one year experienced
      significant (P <0.001) reductions in FI (-2.56 +/- 0.58 mU/L), FG (-0.18 +/- 0.04
      mmol/L), SBP (-2.77 +/- 0.56 mm Hg), TAG (-0.258 +/- 0.037 mmol/L) and BMI (-1.61
      +/- 0.13 kg/m(2)). These risk factor changes were related to a mean calorie
      intake reduction of 273 kcal/d, a mean total fat intake reduction of 6.3%, and 40
      minutes of moderate intensity aerobic exercise four times a week. Lifestyle
      intervention did not have an impact on HDL. More than 99% of total variability in
      the intervention effects was due to heterogeneity. Variability in calorie and fat
      intake restrictions, exercise type and duration, length of the intervention
      period, and the presence or absence of glucose, insulin, or lipid abnormalities
      explained 23-63% of the heterogeneity. CONCLUSIONS: Calorie and total fat intake
      restrictions coupled with moderate intensity aerobic exercises significantly
      improved diabetes risk factors in healthy normoglycemic adults although
      normoglycemic adults with glucose, insulin, and lipid abnormalities appear to
      benefit more.

PMID- 25960773
TI  - Phenotypic heterogeneity of latent autoimmune diabetes in adults identified by
      body composition analysis.
AB  - BACKGROUND: In patients with Latent Autoimmune Diabetes in Adults (LADA) a lower
      body mass index was reported compared with classical type 2 diabetes (T2D), and
      was found to be associated with a faster progression to insulin-dependence. In
      this study we determined the body composition in a cohort of LADA patients from
      Sardinia, Italy, and compared it with age- and gender-matched patients diagnosed
      as having adult-onset type 1 diabetes (T1D) and non-autoimmune T2D. METHODS: In
      210 LADA patients, 210 T2D patients and 30 adult-onset T1D patients of Sardinian
      origin we assessed total and segmental body composition (weight-adjusted percent
      fat mass and lean mass) by using Dual Energy X-rays Absorptiometry (DXA).
      RESULTS: In the whole cohort of LADA patients total fat mass was significantly
      smaller compared with T2D patients (p < 0.0001), while no difference was found
      between LADA and T1D patients. In LADA men fat depletion involved all body
      segments, while in LADA women it was observed only in the truncal segment (p <
      0.0001), as in the upper and lower regions fat deposits were larger compared to
      T2D (p < 0.0001). However, LADA women showed a significantly elevated truncal fat
      compared to T1D women (p < 0.004), whereas no difference was detected in the
      extremities. CONCLUSIONS: Body composition in LADA patients shows substantial
      difference, in a gender-dependent way, compared to classic T2D. In women fat
      deposits tend to accumulate in peripheral regions rather than centrally, whereas
      in men the distribution is more homogeneous. In addition, central fat depletion
      in LADA women appears to be a significant predictor of faster progression to
      insulin dependence. Thus, routine assessment of body composition may help the
      physician identify LADA patients who require early insulin treatment in order to
      delay beta-cell exhaustion, as well those with increased CV risk due to excess
      truncal adiposity.

PMID- 25960775
TI  - A descriptive study of health status and health related quality of life in
      selected outpatients with type 2 diabetes, pathological body mass index and
      cardiovascular risk in Spain.
AB  - BACKGROUND: Ottawa Charter defined health as a resource for everyday life and as
      an important dimension of health related quality of life (HRqol). Diabetes and
      obesity have repeatedly been shown as diseases that diminish health status and
      HRqol. The aim of this study was to measure health status and HRqol in a Spanish
      sample of obese patients with type 2 diabetes at cardiovascular risk and analyze
      behavioural, biological and social determinants of health. METHODS: Outpatients
      from external specialized clinic in Endocrinology were evaluated. MEASUREMENTS:
      sex, age, family history, employment status, comorbidities, pain, lifestyle
      habits, anthropometrics, blood pressure, blood analysis and HRqol with COOP/WONCA
      questionnaire (7 dimensions). STATISTICS: univariate, bivariate, multivariate and
      comparative analysis. RESULTS: Mean age was 59.1 +/- 7.6 [95%IC: 56.6-61.6], 74%
      were women and 63.2% were physically active. WONCA values were; summary index
      (SI): 18.7 +/- 4 [95%IC: 17.3-20] (maximum 35); physical fitness: 3.3 +/- 1,
      feelings: 2.3 +/- 1.1, social activities: 1.5 +/- 1, daily activities: 2.1 +/-
      1.2, change in health: 2.7 +/- 0.9, overall health: 3.6 +/- 0.7 and pain: 3.5 +/-
      1.2 (maximum 5). High fibrinogen values (339.3 +/- 85.8 [95%IC: 309.8-368.8])
      negatively influenced pain visual analogic scale (p = 0.029). Physically active
      patients (63.2%) had better values in daily activities dimension (p = 0.025).
      More than the half of the sample (51.5%) reported a good quality of sleep, but
      the pain worsened it (p = 0.040). High BMI values (34.8 +/- 5.8 [95%IC: 32.9
      36.7]) harmed the COOP-WONCA SI (p = 0.009). High glycated hemoglobin (HbA1c)
      values (6.8 +/- 1.3 [95%IC: 6.3-7.2]) had a negative impact on COOP-WONCA SI (p =
      0.018). Nor tailored diet (15.8%) or being employed (18.4%) influenced the HRqol.
      The regression that best models COOP-WONCA SI was adjusted for BMI and HbA1c. SI
      = 3.509 + 0.335BMI +0.330HbA1c. CONCLUSIONS: HRqol was worse than in general
      population, but better than in previous studies of diabetes patients, without
      differences by sex or age, though feelings, daily activities and pain dimensions
      scored worse than in these studies. Higher levels of HbA1c, obesity and
      procoagulative state had a negative impact in these last dimensions. Pain
      impaired quality of sleep and physical activity had a positive impact in daily
      activities. BMI and HbA1c modeled the HRqol.

PMID- 25960774
TI  - Metabolic and oxidative stress markers in Wistar rats after 2 months on a high
      fat diet.
AB  - BACKGROUND: Metabolic syndrome is associated with an increased risk of
      cardiovascular and hepatic complications. Oxidative stress in metabolic tissues
      has emerged as a universal feature of metabolic syndrome and its co-morbidities.
      We aimed to develop a rapidly and easily induced model of metabolic syndrome in
      rats to evaluate its impact on plasma and tissue oxidative stress. MATERIALS AND
      METHODS: Metabolic syndrome was induced in rats using a high-fat diet (HFD), and
      these rats were compared to rats fed a normal diet (ND) for 2 months. Metabolic
      control was determined by measuring body weight, blood glucose, triglycerides,
      lipid peroxidation and protein carbonylation in plasma. Insulinemia was evaluated
      through the measure of C-peptide. Histological analysis was performed on the
      pancreas, liver and blood vessels. RESULTS: After 2 months, the HFD induced an
      increase in body weight, insulin and triglycerides. Liver steatosis was also
      observed in the HFD group, which was associated with an increase in glycogen
      storage. In the pancreas, the HFD induced islet hyperplasia. Tissue oxidative
      stress was also increased in the liver, pancreas and blood vessels, but plasma
      oxidative stress remained unchanged. CONCLUSION: This paper reports the
      development of a fast and easy model of rat metabolic syndrome associated with
      tissue oxidative stress. This model may be a good tool for the biological
      validation of drugs or antioxidants to limit or prevent the complications of
      metabolic syndrome.

PMID- 25960776
TI  - Realistic changes in monounsaturated fatty acids and soluble fibers are able to
      improve glucose metabolism.
AB  - BACKGROUND/OBJECTIVES: Cardioprotective effects of Mediterranean-style diet have
      been shown. Instead of excluding foods, replacement or addition may facilitate
      compliance with impact on glucose metabolism of individuals at cardiometabolic
      risk. This study investigated the effect of changing selected nutrients intake on
      glucose metabolism during a lifestyle intervention tailored to living conditions
      of prediabetic Brazilians. SUBJECTS/METHODS: 183 prediabetic adults treated under
      the Brazilian public health system underwent an 18-month intervention on diet and
      physical activity. Dietary counseling focused on reducing saturated fat replaced
      by unsaturated fatty acids. Data were collected at baseline and after follow-up.
      ANOVA and multiple linear regression were used to test association of changes in
      nutrients intake with changes in plasma glucose. RESULTS: Changes in fasting and
      2-h plasma glucose but not in weight, HOMA-IR or C-reactive protein decreased
      after intervention across tertiles of MUFA changes (p-trend 0.017 and 0.024,
      respectively). Regression models showed that increase in MUFA intake was
      independently associated with reduction in fasting (beta -1.475, p = 0.008) and 2
      h plasma glucose (beta -3.321, p = 0.007). Moreover, increase in soluble fibers
      intake was associated with decrease in fasting plasma glucose (beta -1.579, p =
      0.038). Adjustment for anthropometric measurements did not change the results but
      did after including change in insulin in the models. CONCLUSIONS: Increases of
      MUFA and soluble fibers intakes promote benefits on glucose metabolism,
      independently of adiposity, during a realistic lifestyle intervention in at-risk
      individuals. Mechanisms mediating these processes may include mainly insulin
      sensitivity improvement.

PMID- 25960777
TI  - Individuals with prediabetes identified by HbA1c undergoing coronary angiography
      have worse cardiometabolic profile than those identified by fasting glucose.
AB  - BACKGROUND: Type 2 diabetes mellitus has well known deleterious effects on
      coronary artery disease (CAD). The role of milder hyperglycemic states such as
      prediabetes (PD) on CAD is debatable. Glycated hemoglobin (HbA1c) has recently
      been advocated as a diagnostic tool for diabetes mellitus (DM) and PD. This study
      aims to assess the cardiometabolic risk profile and coronary lesions of patients
      with PD undergoing coronary angiography identified either by fasting plasma
      glucose (FPG) or HbA1c levels. METHODS: We studied 514 individuals without
      previously known glucose disturbances. Their glycemic status was assessed by FPG
      and HbA1c (HPLC) and classified according to ADA guidelines, using each parameter
      independently, as having normal glucose tolerance (N), PD, or DM. CAD was defined
      as stenosis greater than 50% in one major coronary vessel or branch. Framingham
      score was calculated. RESULTS: Subjects with PD had a similar frequency of CAD
      compared do N individuals by both FPG (61 vs. 59.3%) and HbA1c (55.4 vs 61.2%) (p
      non-significant for linear-by-linear association). PD individuals identified by
      FPG had worse HOMA2B (mean [95% CI] 65.4 [60.9-69.9] vs. 76.6 [71.4-81.9]) and
      HOMA2-IR (1.10 [0.98-1.22] vs. 0.80 [0.72-0.89]) when compared to N controls. PD
      individuals identified by HbA1c had higher frequency of Framingham risk above 20%
      (25.4 vs 11.8%), arterial hypertension (87.8 vs 72.6%), and dyslipidemia (83.8 vs
      72%) compared to N individuals. PD associated with an increased number of
      coronary lesions only when diagnosed by HbA1c (median [interquartile interval] 2
      [0-4] PD versus 1 [0-3.75] N, p = 0.03 for trend). CONCLUSIONS: HbA1c was more
      effective than FPG in identifying individuals with PD associated with high
      cardiovascular risk profile in a sample of individuals undergoing coronary
      angiography.

PMID- 25960778
TI  - Cross-cultural adaptation and validation to Brazilian Portuguese of two measuring
      adherence instruments for patients with type 1 diabetes.
AB  - BACKGROUND: The purpose of this study was to carry out a cross-cultural
      adaptation to Brazilian Portuguese, validation, and comparison of two
      questionnaires to measure adherence in patients with type 1 diabetes. There are
      no validated instruments to measure treatment adherence in Brazilian patients
      with type 1 diabetes. METHODS: Type 1 diabetes outpatients of a tertiary hospital
      in Southern Brazil were recruited to examine psychometric properties of the
      Diabetes Self-Management Profile (DSMP) and Self-Care Inventory-revised (SCI-R)
      adapted to Brazilian Portuguese. Analyses assessed the reliability and validity
      according to its associations with glycated hemoglobin (A1C). Seventy-five
      patients [age: 34.9 +/- 13.7 years; A1C: 9.2 +/- 2% (75 mmol/mol); diabetes
      duration: 18.1 +/- 11.8 years] were evaluated. RESULTS: The translated versions
      of the instruments showed adequate internal consistency (DSMP Cronbach's alpha
      =0.76; SCI-R Cronbach's alpha =0.71). A positive correlation was found between
      all the items and total scores, except for item 12 in DSMP and item 13 in SCI-R,
      and for this reason, these items were excluded from the translated versions. In
      predictive validity analysis, A1C correlated significantly with the DSMP total (r
      = -0.46) and with the SCI-R total (r = -0.44). CONCLUSIONS: The Brazilian
      Portuguese versions of DSMP and SCI-R yielded a reliable and valid tool to
      measure adherence treatment for patients with type 1 diabetes, with a significant
      correlation between total scores and A1C.

PMID- 25960779
TI  - Anthropometric parameters and their associations with cardio-metabolic risk in
      Chinese working population.
AB  - BACKGROUND: There remains controversy regarding which of the anthropometric
      indicators best defines obesity. In this study, we compared the efficacy of using
      body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) in
      the diagnosis of obesity and assessed their associations with diabetes,
      hypertension, and dyslipidemia in an urban working population in China. METHODS:
      Anthropometric measurements, blood pressure, plasma lipids, fasting and 2-hour
      plasma glucose (PG) levels by a 75 gram oral glucose tolerance test (OGTT) were
      obtained from 2603 working Chinese who had no history of cardiovascular diseases
      or diabetes. Cardio-metabolic risk factors including high blood pressure,
      dyslipidemia, and glucose intolerance were evaluated. The diagnoses of overweight
      and obesity were based on the WHO definitions with BMI for general obesity and WC
      and WHR for central obesity. RESULTS: Based on BMI, WC and WHR, there were 31.3%,
      16.6%, 35.2% of the studied subjects, respectively, being overweight and 2.0%,
      5.6%, 9.2% being obese. Among women but not men, more overweight and obese
      subjects were diagnosed using WHR and WC. The number of cardio-metabolic risks
      was higher by WC criterion than BMI and WHR in the whole group (p <0.05) and
      female subjects (p <0.01). Comparing the three anthropometric indexes predicting
      hypertension, hyperglycemia, dyslipidemia and multiple cardio-metabolic risks,
      for women, it was WC having the largest areas under ROC curves (0.759, 0.746,
      0.701 and 0.773 respectively); while in men, it was WC for hypertension, WHR for
      hyperglycemia, BMI for dyslipidemia and WC for multiple cardio-metabolic risks
      (areas under ROC curves were 0.658, 0.686, 0.618 and 0.695 respectively).
      CONCLUSIONS: Among Chinese working population, the need of lower cutoff values to
      define overweight and obesity were observed. Central obesity indicator (WC) is
      the preferred measure to predict the presence of cardio-metabolic risk in Chinese
      female subjects.

PMID- 25960780
TI  - Streptozotocin-induced diabetes disrupts the body temperature daily rhythm in
      rats.
AB  - BACKGROUND: In mammals, the temperature rhythm is regulated by the circadian
      pacemaker located in the suprachiasmatic nuclei, and is considered a "marker
      rhythm". Melatonin, the pineal gland hormone, is a major regulator of the
      endogenous rhythms including body temperature. Its production is influenced by
      many factors, such as type 1 diabetes mellitus. In rats, diabetes leads to
      hypothermia and reduced melatonin synthesis; insulin treatment reestablishes
      both. AIM: To study the body temperature daily rhythm of diabetic animals and the
      effects of insulin and/or melatonin treatment on its structure. METHODS: We
      studied the effects of streptozotocin-induced diabetes (60 mg/kg) on the body
      temperature rhythm of Wistar rats and the possible modifications resulting from
      early and late treatments with insulin (6U/day) and/or melatonin (daily 0.5
      mg/kg). We monitored the daily body temperature rhythm, its rhythmic parameters
      (MESOR, amplitude and acrophase), glycemia and body weight for 55 days. Data were
      classified by groups and expressed as mean +/- SEM. One-way ANOVA analysis was
      performed followed by Bonferroni posttest. Statistical significance was set at p
      < 0.05. RESULTS: Diabetes led to complete disruption of the temperature rhythm
      and hypothermia, which were accentuated over time. All early treatments (insulin
      or/and melatonin) prevented the temperature rhythm disruption and hypothermia.
      Insulin plus melatonin restored the body temperature rhythm whereas insulin alone
      resulted less efficient; melatonin alone did not restore any of the parameters
      studied; however, when supplemented close to diabetes onset, it maintained the
      temperature rhythmicity. All these corrective effects of the early treatments
      were dependent on the continuous maintenance of the treatment. CONCLUSIONS: Taken
      together, our findings show the disruption of the body temperature daily rhythm,
      a new consequence of insulin-dependent diabetes, as well as the beneficial effect
      of the complementary action of melatonin and insulin restoring the normal
      rhythmicity.

PMID- 25960781
TI  - Transition to diversification by competition for multiple resources in catalytic
      reaction networks.
AB  - BACKGROUND: All life, including cells and artificial protocells, must integrate
      diverse molecules into a single unit in order to reproduce. Despite expected
      pressure to evolve a simple system with the fastest replication speed, the
      mechanism by which the use of a great variety of components, and the coexistence
      of diverse cell-types with different compositions are achieved is as yet unknown.
      RESULTS: Here we show that coexistence of such diverse compositions and cell
      types is the result of competitions for a variety of limited resources. We find
      that a transition to diversity occurs both in chemical compositions and in
      protocell types, as the resource supply is decreased, when the maximum inflow and
      consumption of resources are balanced. CONCLUSIONS: Our results indicate that a
      simple physical principle of competition for a variety of limiting resources can
      be a strong driving force to diversify intracellular dynamics of a catalytic
      reaction network and to develop diverse protocell types in a primitive stage of
      life.

PMID- 25960783
TI  - Effects of phthalate exposure on asthma may be mediated through alterations in
      DNA methylation.
AB  - BACKGROUND: Phthalates may increase the asthma risk in children. Mechanisms
      underlying this association remain to be addressed. This study assesses the
      effect of phthalate exposures on epigenetic changes and the role of epigenetic
      changes for asthma. In the first step, urine and blood samples from 256 children
      of the Childhood Environment and Allergic diseases Study (CEAS) were analyzed.
      Urine 5OH-MEHP levels were quantified as an indicator of exposure, and asthma
      information was collected. DNA methylation (DNA-M) was measured by quantitative
      PCR. In the screening part of step 1, DNA-M of 21 potential human candidate genes
      suggested by a toxicogenomic data were investigated in 22 blood samples. Then, in
      the testing part of step 1, positively screened genes were tested in a larger
      sample of 256 children and then validated by protein measurements. In step 2, we
      replicated the association between phthalate exposure and gene-specific DNA-M in
      54 children in the phthalate contaminated food event. In step 3, the risk of DNA
      M for asthma was tested in 256 children from CEAS and corroborated in 270
      children from the Isle of Wight (IOW) birth cohort. RESULTS: Differential
      methylation in three genes (AR, TNFalpha, and IL-4) was identified through
      screening. Testing in 256 children showed that methylation of the TNFalpha gene
      promoter was lower when children had higher urine 5OH-MEHP values (beta = -0.138,
      P = 0.040). Functional validation revealed that TNFalpha methylation was
      inversely correlated with TNFalpha protein levels (beta = -0.18, P = 0.041). In
      an additional sample of 54 children, we corroborated that methylation of the
      TNFalpha gene promoter was lower when urine 5OH-MEHP concentrations were higher.
      Finally, we found that a lower methylation of 5'CGI region of TNFalpha was
      associated with asthma in 256 CEAS children (OR = 2.15, 95% CI = 1.01 to 4.62).
      We replicated this in 270 children from the IOW birth cohort study. Methylation
      of the CpG site cg10717214 was negatively associated with asthma, when children
      had 'AA' or 'AG' genotype of the TNFalpha single nucleotide rs1800610.
      CONCLUSIONS: Effects of phthalate exposure on asthma may be mediated through
      alterations in DNA methylation.

PMID- 25960782
TI  - Evolution of group II introns.
AB  - Present in the genomes of bacteria and eukaryotic organelles, group II introns
      are an ancient class of ribozymes and retroelements that are believed to have
      been the ancestors of nuclear pre-mRNA introns. Despite long-standing
      speculation, there is limited understanding about the actual pathway by which
      group II introns evolved into eukaryotic introns. In this review, we focus on the
      evolution of group II introns themselves. We describe the different forms of
      group II introns known to exist in nature and then address how these forms may
      have evolved to give rise to spliceosomal introns and other genetic elements.
      Finally, we summarize the structural and biochemical parallels between group II
      introns and the spliceosome, including recent data that strongly support their
      hypothesized evolutionary relationship. 

PMID- 25960784
TI  - Coordinated epigenetic remodelling of transcriptional networks occurs during
      early breast carcinogenesis.
AB  - BACKGROUND: Dysregulation of the epigenome is a common event in malignancy;
      however, deciphering the earliest cancer-associated epigenetic events remains a
      challenge. Cancer epigenome studies to date have primarily utilised cancer cell
      lines or clinical samples, where it is difficult to identify the initial
      epigenetic lesions from those that occur over time. Here, we analysed the
      epigenome of human mammary epithelial cells (HMEC) and a matched variant cell
      population (vHMEC) that have spontaneously escaped senescence and undergone
      partial carcinogenic transformation. Using this model of basal-like breast
      carcinogenesis, we provide striking new insights into the very first epigenetic
      changes that occur during the initial stages of malignancy. RESULTS: The first
      phase of malignancy is defined by coordinated changes in the epigenome. At the
      chromatin level, this is embodied in long-range epigenetic deregulation, which
      involves the concomitant but atypical acquisition or loss of active and
      repressive histone modifications across large regional blocks. Changes in DNA
      methylation also occurs in a highly coordinated manner. We identified
      differentially methylated regions (DMRs) in the very earliest passages of vHMECs.
      Notably, we find that differential methylation targets loci regulated by key
      transcription factors including p53, AHR and E2F family members suggesting that
      epigenetic deregulation of transcription factor binding is a key event in breast
      carcinogenesis. Interestingly, DMRs identified in vHMEC are extensively
      methylated in breast cancer, with hypermethylation frequently encroaching into
      neighbouring regions. A subset of vHMEC DMRs exhibited a strong basal-like cancer
      specific hypermethylation. CONCLUSIONS: Here, we generated epigenome-wide maps of
      the earliest phase of breast malignancy and show long-range epigenetic
      deregulation and coordinated DNA hypermethylation targets loci regulated by key
      transcription factors. These findings support a model where induction of breast
      cancer occurs through epigenetic disruption of transcription factor binding
      leading to deregulation of cancer-associated transcriptional networks. With their
      stability and very early occurrence, vHMECs hypermethylated loci could serve as
      excellent biomarkers for the initial detection of basal breast cancer.

PMID- 25960785
TI  - New minimally invasive technique of parastomal hernia repair - methods and
      review.
AB  - INTRODUCTION: Parastomal hernia is described as the most common complication in
      patients with ostomy. It is reported that its incidence varies from 3% to 39% for
      colostomies and 0 to 6% for ileostomies. Surgical repair remains the treatment of
      choice. There are three types of surgical treatment - fascial repair, stoma
      relocation and repair using prosthetic mesh via a laparoscopic or open approach.
      Recently there have been several meta-analyses and systematic reviews aiming to
      compare the results of surgical treatment, and the authors agreed that the
      quality of evidence precludes firm conclusions. AIM: To describe the novel
      concept of parastomal hernia repair - HyPER/SPHR technique (hybrid parastomal
      endoscopic re-do/Szczepkowski parastomal hernia repair) and its early results in
      12 consecutive cases. MATERIAL AND METHODS: Twelve consecutive patients were
      operated on due to parastomal hernia using the new HyPER hybrid technique between
      June 2013 and May 2014. The patients' condition was evaluated during the
      perioperative period, 6 weeks and then every 3 months after surgery. RESULTS:
      After 6 weeks of follow-up we have not observed any mesh-related complications.
      All 12 patients were examined 3 months and 6 months after repair surgery for
      evaluation. No recurrence, stoma site infection or stoma-related problems were
      found. None of the patients complained of pain and none of them needed to be
      hospitalized again. Reported quality of life on a 0-10 scale after 6 weeks of
      follow-up was 8 (range: 7-10). CONCLUSIONS: The HyPER procedure for treatment of
      parastomal hernias proposed by the authors is a safe and feasible surgical
      technique with a high patient satisfaction rate and a low number of
      complications. The hybrid procedure seems to be a promising method for parastomal
      hernia repair.

PMID- 25960786
TI  - If the clinical experience is very important for everyday practice....

PMID- 25960787
TI  - Incidence of true short esophagus among patients submitted to laparoscopic Nissen
      fundoplication.
AB  - INTRODUCTION: The last two decades have observed development of surgical
      treatment of benign conditions of the gastroesophageal junction (GEJ), including
      anti-reflux surgery, due to the growing popularity of the laparoscopic approach.
      Migration of the fundoplication band and recurrent hiatal hernia are a result of
      the lack of correct diagnosis and appropriate management of the so-called short
      esophagus. According to various authors, short esophagus is present in up to 60%
      of patients qualified for anti-reflux surgery. However, some researchers question
      the existence of this condition. AIM: To analyze the prevalence of short
      esophagus in patients subjected to laparoscopic Nissen fundoplication. MATERIAL
      AND METHODS: The study included 202 patients who were subjected to laparoscopic
      Nissen fundoplication. RESULTS: As many as 96% of the patients qualified for the
      surgical treatment showed supradiaphragmatic location of the high pressure zone.
      The extent of GEJ protrusion ranged from 0 cm to 3 cm (mean: 2 cm). The extent of
      dissection within the mediastinum was determined by the level of GEJ protrusion,
      and ranged from 5 cm to 12 cm (mean: 6 cm). Upon complete mobilization of the
      esophagus within the mediastinum, no cases of significantly shortened esophagus,
      precluding downward retraction of at least a 2.5-cm segment below the
      diaphragmatic crura, were documented. Therefore, none of the patients required
      Collis gastroplasty. CONCLUSIONS: The presence of "true" short esophagus is a
      sporadic finding among patients qualified for anti-reflux surgery. Mediastinal
      dissection of the esophagus and its mobilization at an appropriate, individually
      defined level seems a sufficient treatment in the vast majority of these
      patients.

PMID- 25960788
TI  - Assessment of the efficacy and safety of steam vein sclerosis as compared to
      classic surgery in lower extremity varicose vein management.
AB  - INTRODUCTION: For the last 10 years, endovenous thermal ablation methods have
      gradually predominated over the classic Babcock procedure in varicose vein
      treatment. Steam vein sclerosis is the newest thermal ablation technique. AIM: To
      assess the efficacy and safety of steam vein sclerosis as compared to the Babcock
      procedure in lower extremity varicose vein treatment. MATERIAL AND METHODS: One
      hundred and two adult subjects with varicose veins of clinical grade C2 to C6
      according to the CEAP classification, treated with varicose vein surgery between
      2010 and 2012, were enrolled in the study. These were subdivided into two groups:
      the study group of 52 patients treated with endovenous steam vein sclerosis and
      the control group of 50 patients treated with the Babcock procedure. A single
      lower extremity with isolated great or small saphenous vein insufficiency was
      operated on in each subject. The groups were compared for demography, disease
      severity, involved veins, potential perioperative and postoperative
      complications, as well as treatment efficacy based on the VCSS score reduction.
      RESULTS: There were no statistically significant differences between the groups
      in terms of demography, disease severity, involved veins, or perioperative and
      postoperative complications. The treatment efficacy of both methods, assessed
      based on the recurrence rate and the quantitative VCSS score reduction, was
      similar. Clinically significant recanalisation was observed in 1 (1.9%) patient
      in the study group. CONCLUSIONS: The efficacy and safety analysis shows that
      steam vein sclerosis is a safe, simple method which can be recommended as
      effective varicose vein treatment.

PMID- 25960789
TI  - Laparoscopic pyeloplasty with cephalad translocation of the crossing vessel - a
      new approach to the Hellstrom technique.
AB  - INTRODUCTION: It is believed that lower pole crossing vessels may play an
      important role in the etiology of ureteropelvic junction obstruction (UPJO). A
      conventional operative technique, which seems to be widely used in patients with
      UPJO, is Anderson-Hynes (A-H) plasty with dorsal transposition of the vessel. An
      attractive alternative to dorsal transposition of the vessel might be its
      cephalad translocation. AIM: To assess the effectiveness of cephalad
      translocation of the crossing vessel in patients who underwent laparoscopic A-H
      or Y-V pyeloplasty. MATERIAL AND METHODS: Eighty-five patients were included in
      the study. To assess the effectiveness of cephalad translocation of the crossing
      vessel in patients who underwent laparoscopic pyeloplasty, the results of the
      procedure were compared to the results of laparoscopic pyeloplasties performed in
      patients without crossing vessels (control group). Success was defined as the
      following factors taken collectively: 80% or greater pain relief according to
      VAS, no sign of obstruction on intravenous urography (patent UPJ), decreasing
      excretion curve with T1/2 < 12 min, and improved or stable differential renal
      function on diuretic renography. RESULTS: The mean follow-up was 53.7 months.
      There was no statistically significant difference in the success rate between the
      compared groups (group 1 - cases with cephalad translocation of the crossing
      artery, and group 2 - cases without crossing vessels) in patients who underwent A
      H plasty or Y-V plasty. CONCLUSIONS: The analysis of our data seems to indicate
      that cephalad translocation of the anterior crossing vessel gives good
      therapeutic results in patients who undergo laparoscopic pyeloplasty.

PMID- 25960790
TI  - Enhanced recovery after colorectal surgery in elderly patients.
AB  - INTRODUCTION: The elderly will soon constitute 20% of the population. Their
      number is constantly rising, particularly in developed countries. It was found
      that they particularly benefit from the use of minimally invasive surgery. The
      Enhanced Recovery After Surgery (ERAS) protocol may further improve clinical
      outcomes in this group of patients. AIM: To assess the implementation of the ERAS
      protocol in elderly patients submitted to laparoscopic colorectal surgery.
      MATERIAL AND METHODS: Ninety-two patients who underwent elective laparoscopic
      colorectal surgery were included in the study. Patients were divided into group 1
      (<= 65 years) and group 2 (> 65 years). Perioperative care was based on ERAS
      Society guidelines. Length of hospital stay, time of first stool passage,
      perioperative complications and readmissions were analyzed. RESULTS: Group 2
      patients had higher ASA grades in comparison to group 1. In all cases, oral fluid
      intake started on the day of surgery. The groups did not differ according to oral
      fluid tolerance, first stool passage time or length of hospital stay. Number and
      character of perioperative complications were comparable between the two groups.
      Four patients were readmitted within 30 days after discharge. One patient
      required reoperation. CONCLUSIONS: Implementation of the ERAS protocol is
      possible regardless of the age of surgical patients. Its use in the elderly
      allows the length of hospitalization to be shortened and is not associated with
      higher risk of postoperative complications or readmissions.

PMID- 25960791
TI  - Comparison of the short-term postoperative results of prone positioning and
      lateral decubitus positioning during thoracoscopic esophagectomy.
AB  - INTRODUCTION: The conventional approach during thoracoscopic esophagectomy was
      performed in the left lateral decubitus position (LLDP). Recently, thoracoscopic
      esophagectomy in the prone position (PP) has attracted the attention of surgeons.
      AIM: To report institutional experience with thoracoscopic esophagectomy in PP
      and compare it with the conventional LLDP approach. MATERIAL AND METHODS: We
      reviewed 59 consecutive patients who had presented with esophageal cancer
      undergoing three-stage thoracoscopic/laparoscopic esophagectomy (TLE) from May
      2011 to Dec 2013. The TLE was sequentially performed on enrolled patients in LLDP
      from May 2011 to Oct 2012 and in PP from Nov 2012 to Dec 2013. Immediate
      postoperative outcomes were collected and compared to determine differences
      between the 2 groups. RESULTS: Thirty-eight patients had their operations in LLDP
      and 21 in PP. No differences in blood loss, respiratory condition during surgery,
      or postoperative pain scores were observed between the 2 groups. The PP had a
      shorter thoracic stage duration (3.4 vs. 3.9 h; p = 0.03) and shorter intensive
      care unit (ICU) stay (1.0 vs. 1.5 days; p = 0.03) but yielded a similar number of
      lymph nodes. Incidence of complications was similar between the 2 groups, except
      significantly lower incidence of pneumonia in PP (0% vs. 21.1%; p = 0.04) and
      higher incidence of hoarseness in PP (52.4% vs. 23.7%; p = 0.03). The symptoms
      resolved within 3 months in all patients except in the 2 patients with vocal cord
      palsy. CONCLUSIONS: It is feasible and safe to perform thoracoscopic
      esophagectomy by adopting the prone position. Thoracoscopic esophagectomy in the
      prone position is potentially associated with fewer major complications and
      shorter ICU stay.

PMID- 25960792
TI  - The role of laparoscopy in the surgical treatment of endometrial cancer.
AB  - INTRODUCTION: Endometrial carcinoma is one of the most common neoplasms in
      gynecological oncology and the most common genital cancer in women in developed
      countries. The 5-year overall survival rate depends on the FIGO stage. For
      patients with stage I endometrial cancer it is estimated as 80%. Traditionally,
      the main treatment of endometrial cancer consists of total abdominal hysterectomy
      with bilateral salpingo-oophorectomy and, in some histological or clinical
      stages, with additional pelvic lymphadenectomy. The main surgical approach so far
      for women with endometrial cancer has been laparotomy. However, in the last
      decades there have been many reports stating that the survival rate in such cases
      is similar after laparoscopy and laparotomy. Some researchers claim that
      laparoscopy is as effective as laparotomy, and it might be much more precise than
      laparotomy thanks to its special optic system. AIM: To establish the method of
      choice for treatment of stage I endometrial cancer. MATERIAL AND METHODS:
      Comparing the preliminary results from data collected during surgical procedures
      performed at the First Department of Obstetrics and Gynecology of the Medical
      Centre of Postgraduate Education in Warsaw and the Department of Obstetrics and
      Gynecology of the Rural Hospital in Garwolin. RESULTS: Laparoscopy is as
      effective as laparotomy, and it might be much more precise than laparotomy.
      CONCLUSIONS: Taking into consideration all the above arguments, if an experienced
      endoscopic surgeon and proper laparoscopic equipment are available, laparoscopy
      might become the method of choice for treatment of stage I endometrial cancer.

PMID- 25960793
TI  - The management of abdominal wall hernias - in search of consensus.
AB  - INTRODUCTION: Laparoscopic repair is becoming an increasingly popular alternative
      in the treatment of abdominal wall hernias. In spite of numerous studies
      evaluating this technique, indications for laparoscopic surgery have not been
      established. Similarly, implant selection and fixation techniques have not been
      unified and are the subject of scientific discussion. AIM: To assess whether
      there is a consensus on the management of the most common ventral abdominal wall
      hernias among recognised experts. MATERIAL AND METHODS: Fourteen specialists
      representing the boards of European surgical societies were surveyed to determine
      their choice of surgical technique for nine typical primary ventral and
      incisional hernias. The access method, type of operation, mesh prosthesis and
      fixation method were evaluated. In addition to the laparoscopic procedures, the
      number of tackers and their arrangement were assessed. RESULTS: In none of the
      cases presented was a consensus of experts obtained. Laparoscopic and open
      techniques were used equally often. Especially in the group of large hernias,
      decisions on repair methods were characterised by high variability. The technique
      of laparoscopic mesh fixation was a subject of great variability in terms of both
      method selection and the numbers of tackers and sutures used. CONCLUSIONS:
      Recognised experts have not reached a consensus on the management of abdominal
      wall hernias. Our survey results indicate the need for further research and the
      inclusion of large cohorts of patients in the dedicated registries to evaluate
      the results of different surgical methods, which would help in the development of
      treatment algorithms for surgical education in the future.

PMID- 25960794
TI  - Thoracoscopic repair of esophageal atresia with a distal fistula - lessons from
      the first 10 operations.
AB  - INTRODUCTION: Thoracoscopic esophageal atresia (EA) repair was first performed in
      1999, but still the technique is treated as one of the most complex pediatric
      surgical procedures. AIM: The study presents a single-center experience and
      learning curve of thoracoscopic repair of esophageal atresia and tracheo
      esophageal (distal) fistula. MATERIAL AND METHODS: From 2012 to 2014, 10
      consecutive patients with esophageal atresia and tracheo-esophageal fistula were
      treated thoracoscopically in our center. There were 8 girls and 2 boys. Mean
      gestational age was 36.5 weeks and mean weight was 2230 g. Four children had
      associated anomalies. The surgery was performed after stabilization of the
      patient between the first and fourth day after birth. Five patients required
      intubation before surgery for respiratory distress. Bronchoscopy was not
      performed before the operation. RESULTS: In 8 patients, the endoscopic approach
      was successfully used thoracoscopically, while in 2 patients conversion to an
      open thoracotomy was necessary. In all patients except 1, the anastomosis was
      patent, with no evidence of leak. One patient demonstrated a leak, which did not
      resolve spontaneously, necessitating surgical repair. In long-term follow-up, 1
      patient required esophageal dilatation of the anastomosis. All patients are on
      full oral feeding. CONCLUSIONS: The endoscopic approach is the method of choice
      for the treatment of esophageal atresia in our center because of excellent
      visualization and precise atraumatic preparation even in neonates below a weight
      of 2000 g.

PMID- 25960796
TI  - Assessment of patients' quality of life after haemorrhoidectomy using the
      LigaSure device.
AB  - INTRODUCTION: Haemorrhoids are small anatomical structures within the anal canal
      that are involved in the proper functioning of the lower gastrointestinal tract.
      Factors favouring the development of haemorrhoidal disease are insufficient
      physical activity, prolonged sitting and hence a shortage of physical activity,
      as well as poor diet which lacks adequate amounts of fibre. The main symptom of
      this disease is bleeding with bright red blood just after defecation.
      Haemorrhoidal disease occurs when the ligamentous apparatus comes loose and the
      internal haemorrhoidal plexus translocates down, whereas haemorrhoids enlarge and
      move out of the anal canal. Haemorrhoidal disease treatment includes
      conservative, instrumental and surgical therapy. AIM: To assess treatment and
      satisfaction in particular life domains after haemorrhoidectomy. MATERIAL AND
      METHODS: The research was undertaken in the General, Thoracic and Vascular
      Surgery Clinic of the 10(th) Military Clinical Hospital with Polyclinic in
      Bydgoszcz among 50 patients treated due to haemorrhoids and operated on in the
      period 2007-2008. The study evaluated quality of patients' life after
      haemorrhoidectomy by Ferguson's method using a LigaSure appliance. RESULTS: The
      study investigated whether patients perceived a difference before and after
      surgery. The research proved that patients can describe disease symptoms and know
      the risk factors for haemorrhoids. In the studied group patients are able to
      describe characteristic signs of haemorrhoidal disease and also indicate
      differences in everyday life before and after the surgery. They can also describe
      and classify the pain before and 1 year after the haemorrhoidectomy, which was
      statistically significantly lower already 3 months after the operation.
      CONCLUSIONS: Conducted examinations showed that sick people in the precise way
      were able to determine manifestations and know risk factors of the prevalence of
      disease hemorrhoidal. Operated sick people indicated the difference in quality of
      the life both before, as well as after the undergone treatment. After the
      operation of the haemorrhoids with method of Ferguson using LigaSure apparatus
      operated sick persons could distinguish and classify pain before the treatment as
      well as in a year after which was statistically characteristically lower already
      after three months from treatment.

PMID- 25960795
TI  - Laparoscopic urinary bladder diverticulectomy combined with photoselective
      vaporisation of the prostate.
AB  - INTRODUCTION: Pseudodiverticulum of the urinary bladder is mostly a complication
      of subvesical obstruction (SO). The gold standard of treatment was open
      diverticulectomy with adenectomy. A more contemporary resolution is endoscopic,
      in two steps: the first transurethral resection of the prostate (TURP), the
      second laparoscopic diverticulectomy (LD). AIM: To present a one-session
      procedure - photoselective vaporisation of the prostate (PVP) with LD. MATERIAL
      AND METHODS: From 1/2011 to 6/2014, 14 LDs were performed: 1 LD only, 1 with
      laparoscopic radical prostatectomy, 12 combined with treatment of benign
      prostatic hyperplasia (BPH), 4 cases of TURP and LD in the second period. In 8
      cases, PVP and LD in one session were combined. These 8 cases are presented. 3D
      CT cystography was used as a gold standard for assessment of diverticulum.
      RESULTS: The mean age was 66.5 +/-5.5 (57.3-75.1) years, the mean size of the
      diverticulum 61.8 +/-22.1 (26-90) mm. The procedure starts in the lithotomy
      position. It includes PVP and stenting of the ureter(s). Changing of position and
      laparoscopy follows: four ports, transperitoneal extravesical approach.
      Photoselective vaporisation of the prostate was performed using the Green Light
      Laser HPS (1x) or XPS with cooled fibre MoXy (7x). The mean delivered energy in
      PVP was 205.1 +/-106.4 (120-458) kJ. The mean time of operation was 165.0 +/-48.5
      (90-255) min. No postoperative complications were observed. One patient underwent
      TUR incision after 1 year for sclerosis of the bladder neck. CONCLUSIONS:
      Pseudodiverticulum of the urinary bladder (with or without SO) is a relatively
      rare disease. One session of PVP (Green Light Laser XPS, MoXy fibre) and
      laparoscopic (transperitoneal extravesical) diverticulectomy is the preferred
      method for treatment of subvesical obstruction due to BPH and bladder
      diverticulum at our institution.

PMID- 25960797
TI  - Laparoscopic colorectal surgery for colorectal polyps: single institution
      experience.
AB  - INTRODUCTION: Because of their difficult location or size, some polyps are
      impossible to remove with a flexible colonoscope and must be surgically removed.
      Laparoscopy is a great alternative. AIM: To assess outcomes of a laparoscopic
      approach for the management of difficult colorectal polyps. MATERIAL AND METHODS:
      From 2006 to 2014, patients with polyps that could not be treated by endoscopy
      were included. Demographic data, histology of the biopsy, type of surgery, length
      of postoperative stay, complications and final pathology were reviewed
      prospectively. RESULTS: Forty-two patients with a mean age of 64.9 +/-8.4
      underwent laparoscopic polypectomy. Laparoscopic mobilization of the colonic
      segment and colotomy with removal of the polyp was performed for 12 (28.6%)
      polyps. Laparoscopic segmental bowel resection was performed in 30 (71.4%) cases:
      anterior rectal resection with partial total mesorectal excision in 12 (28.6%),
      left hemicolectomy in 7 (16.6%), sigmoid resection in 6 (14.3%), ileocecal
      resection in 2 (4.76%), resection of transverse colon in 2 (4.76%) and sigmoid
      resection with transanal retrieval of specimen in 1 (2.38%). Mean postoperative
      hospital stay was 5.9 +/-2.6 days. There were 4 complications (9.5%). All
      patients recovered after conservative treatment. Mean polyp size was 3.6 +/-2.2
      cm. Final pathology revealed polyps (n = 2), tubular adenoma (n = 6),
      tubulovillous adenoma (n = 20), carcinoma in situ (n = 10) and invasive cancer (n
      = 4). Two of these patients underwent laparoscopic left hemicolectomies 14 and 10
      days after laparoscopic colotomy and polypectomy. CONCLUSIONS: For the management
      of endoscopically unresectable polyps, laparoscopic polypectomy is currently the
      technique of choice.

PMID- 25960798
TI  - Video display during laparoscopy - where should it be placed?
AB  - INTRODUCTION: During laparoscopy, the monitor is usually placed near the
      operating table, at eye level, which significantly affects hand-eye coordination.
      First, it is impossible for the surgeon to simultaneously observe the operative
      field and hand movement. Second, the axis of view of the endoscope rarely matches
      the natural axis of the surgeon's sight: it resembles a direct view into the
      operative field. Finally, as the arms of the tools act as levers with a fulcrum
      at the site of the skin incision, the action of the tool handles is a mirror
      image of the movement of the tool tips seen on the monitor. Studies have shown
      that a neutral position with the head flexed at 15-45 degrees  is the most
      ergonomically suitable. AIM: To evaluate whether the level of monitor placement
      exerts an influence on laparoscopic performance. MATERIAL AND METHODS: A group of
      52 students of medicine were asked to pass a thread through 9 holes of different
      sizes, placed at different levels and angles, using a self-made laparoscopic
      simulator. Each student performed the task four times in two monitor positions:
      at eye level, and placed on a simulator. The order of monitor placement was
      randomized. RESULTS: The task was performed more quickly when the monitor was
      placed on the simulator and the sight was forced downwards. Lower placement was
      also found to be more beneficial for students with experience in laparoscopy.
      CONCLUSIONS: New technologies which place the display on the patient, thus
      improving the ergonomics of the operation, should be developed.

PMID- 25960799
TI  - Selected oxidative stress markers in gynecological laparoscopy.
AB  - INTRODUCTION: The surgical stress response after laparoscopy is smaller when
      compared with open surgery, and it is expected that after minimally invasive
      surgery the possible development of oxidative stress will be less severe. AIM: To
      evaluate markers of pro-oxidant activity - levels of lipid peroxides and
      malondialdehyde - and activity of the antioxidant enzymes superoxide dismutase
      and glutathione peroxidase in the perioperative period in patients undergoing
      gynecological laparoscopy and to determine whether the duration of laparoscopy
      can affect these changes. MATERIAL AND METHODS: The study included 64 patients,
      divided into two groups: group 1 with duration of laparoscopy up to 20 min, and
      group 2 with duration of the operation over 40 min. Blood samples were collected
      before anesthesia, 5 min after release of pneumoperitoneum, and 10 h after
      surgery. RESULTS: A statistically significant increase in the levels of lipid
      peroxides and malondialdehyde in samples collected after surgery was found in
      comparison with values obtained before surgery. Also statistically significant
      differences existed between groups of patients with different duration of
      surgery. Superoxide dismutase and glutathione peroxidase activity values were
      significantly decreased. They were also significantly different between the two
      groups with different duration of surgery. CONCLUSIONS: In our study, levels of
      the markers of pro-oxidant activity increased and levels of the markers of
      antioxidant enzymes decreased, suggesting development of oxidative stress. The
      duration of laparoscopic procedures affects the severity of the presented
      changes.

PMID- 25960800
TI  - The role of laparoscopy in the management of pediatric appendicitis: a survey of
      Polish pediatric surgeons.
AB  - INTRODUCTION: Despite the increase in use of laparoscopic appendectomy (LA) in
      recent years, until now no nationwide survey on this issue has been performed in
      Poland. AIM: To determine current surgical practice patterns among Polish
      pediatric surgeons in the treatment of appendicitis in children. MATERIAL AND
      METHODS: The nationwide survey was conducted in the form of an internet
      questionnaire asking for information concerning treatment of children suspected
      of having acute appendicitis in the years 2007-2011. Twenty-seven major pediatric
      surgical departments in Poland were invited to participate in the study. RESULTS:
      The overall survey response rate was 70.37%. Laparoscopic appendectomy was
      offered in all departments except one. Laparoscopy was used in 33% of cases and
      was the standard procedure in 4 departments. In 1 center 100% of appendectomies
      were performed laparoscopically. The 3-port technique was used in all
      departments. Five centers offered transumbilical laparoscopic extracorporeal
      appendectomy and 2 centers single-port appendectomy. In LA the mesoappendix was
      mostly divided using bipolar or monopolar coagulation and the appendix was
      ligated using endoloops or was clipped. The mean hospitalization time was 3.31
      days after laparoscopy and 5.47 days after open appendectomy. CONCLUSIONS:
      Despite an apparent consensus on some aspects of pediatric appendicitis among
      Polish pediatric surgeons, significant inconsistency exists in the operative
      approach. The low rate of LA suggests that LA still remains far from being a
      standard. Personal experience and preference have a major influence on the choice
      of operative approach. It is recommended that national guidelines be set up,
      which could standardize the care for children and training of pediatric surgery
      residents.

PMID- 25960801
TI  - Minimally invasive transxiphoid approach for management of pediatric cardiac
      tamponade - one center's experience.
AB  - INTRODUCTION: Cardiac tamponade is excessive collection of fluid in the
      pericardial sac surrounding the heart that leads to restriction of cardiac
      function and causes critical cardiogenic shock and rapid circulatory depression.
      Despite the potential variety of different etiologies in the face of a dangerous
      decrease of cardiac output, the emergency life-saving procedure is surgical
      pericardial fluid evacuation. AIM: To perform a retrospective analysis of
      clinical data and the results of minimally invasive transxiphoid pediatric
      cardiac tamponade evacuation procedures performed in a cardiac surgery center.
      MATERIAL AND METHODS: We performed a retrospective analysis of all consecutive
      patients referred for treatment in our department in a period of 6 years (15
      patients) who underwent emergency pericardial drainage after an
      echocardiographically proven diagnosis. The procedure of choice was minimally
      invasive transxiphoid fluid evacuation with routine pericardial drainage.
      Retrospective operative data analysis was performed: clinical symptoms, pre
      admission and initial emergency diagnostics and interventions, the morphology and
      total amount of drained pericardial fluid, length of stay, final results, and
      overall survival rate. We introduced an original pediatric tamponade index (PTI).
      The PTI was analyzed according to catecholamine support before the drainage and
      the length of hospital stay after the procedure. RESULTS: All patients survived
      the procedure. No early complications of the presented minimally invasive
      subxiphoid approach were noted. Mean PTI in patients with intensive catecholamine
      support before the operation was significantly higher than in patients without
      it. CONCLUSIONS: Minimally invasive surgical transxiphoid interventions appear to
      be a safe and effective method to provide life-saving support with retrieval of
      the fluid for further laboratory investigations.

PMID- 25960802
TI  - The impact of bariatric surgery on nutritional status of patients.
AB  - INTRODUCTION: Currently, surgical treatment is considered to be the most
      efficient method of dealing with morbid obesity. AIM: To evaluate changes in
      nutritional status after surgical treatment of obesity in the early postoperative
      period. MATERIAL AND METHODS: The study included 50 patients (30 women and 20
      men) treated surgically due to morbid obesity. During the preliminary visit and
      during control visits measurements of body mass, height, and waist and hip
      circumference were conducted. Also, analysis of body content was performed and
      blood was taken for biochemical analysis. Statistical analysis was conducted
      using the program Statistica 10. RESULTS: Six months after the surgery, in the
      group of women, significant reduction of average body mass, average waist
      circumference, average hip circumference and average body mass index (BMI) was
      observed. Also, significant reduction of the percentage of body fat and an
      increase in the percentage of fat-free body mass were observed. A significant
      decrease in muscle mass was also noted. Both in women and in men, 6 months after
      the surgery, a significant decrease in fasting glucose concentration, fasting
      insulin and triglycerides in blood serum was observed. CONCLUSIONS: Bariatric
      procedures lead to significant body mass, BMI, waist and hip circumference
      reduction. Loss of body mass is caused mainly by the reduction of fat tissue.
      Application of surgical procedures in morbid obesity treatment also allowed us to
      achieve improvement in insulin, glucose and lipid metabolism.

PMID- 25960803
TI  - Subxiphoid single-incision thoracoscopic surgery for bilateral primary
      spontaneous pneumothorax.
AB  - It has been reported that single-incision thoracoscopic surgery can reduce
      postoperative pain without compromising the main surgical steps required for
      treating patients affected by primary spontaneous pneumothorax. However, all the
      reported thoracoscopic surgery cases with a single-incision procedure were via
      the intercostal route for unilateral pulmonary lesions. We present a novel single
      incision thoracoscopic technique via a subxiphoid route to perform one-stage
      bilateral thoracoscopic surgery for bilateral spontaneous pneumothorax. Reduced
      postoperative pain, shorter operative time, and better cosmetic results are
      potential benefits of this technique in selected patients. The subxiphoid single
      incision procedure may be indicated in patients with bilateral pulmonary lesions
      requiring surgical resections. 

PMID- 25960804
TI  - Extraction of a foreign body in the liver using single incision laparoscopic
      surgery: a new application for minimally invasive surgical procedures.
AB  - Ingestion of foreign bodies is a common medical problem frequently observed in
      children, psychiatric patients and prisoners. Various cases have been found in
      the medical literature, with different diagnostic and therapeutic approaches. We
      report a case of a 41-year-old male inmate, hospitalized for right upper quadrant
      pain of the abdomen due to the ingestion of two syringe needles two weeks
      previously. We describe the diagnostic procedure and the removal of one of the
      two needles that had migrated into the liver parenchyma, using a single-incision
      laparoscopic surgical technique. The operation was carried out safely through a
      2.5 cm transverse incision below the umbilicus. The dissection and the removal of
      the foreign body were easily conducted under direct visualization using a
      minimally invasive surgical technique. Our case report demonstrates the efficacy
      and the security of the laparoscopic treatment in such a challenging area,
      employing a single port access only. 

PMID- 25960805
TI  - Laparoscopic assisted total gastrectomy for gastric cancer - operative technique.
AB  - For many years, open gastrectomy with lymphadenectomy was the gold standard
      treatment for gastric cancer. In recent years, however, laparoscopic assisted
      total gastrectomy with associated D2 lymphadenectomy has gained in popularity. It
      has a similar oncological outcome to open resection, but has all of the added
      advantages of a laparoscopic procedure, such as early mobilisation, less
      postoperative pain and shorter hospital stay. This article describes the
      operative techniques, including key procedure steps, as well as a guide for using
      the new OrVil device for the laparoscopic creation of the oesophago-jejunal
      anastomosis. A video of a laparoscopic assisted total gastrectomy is presented. 

PMID- 25960806
TI  - Mondor's disease in a patient after a mammotome biopsy.
AB  - Mondor's disease is a rare, benign condition characterised by thrombophlebitis
      affecting subcutaneous veins of the chest and/or abdomen without an accompanying
      inflammatory response. The disease has a multifactorial etiology and its course
      is benign. It is usually self-limiting or it is eliminated by local treatment.
      Mondor's disease in the thoracoepigastric region may be a rare complication of
      mammotome biopsy. The case presentation describes a 32-year-old patient with
      Mondor's disease in the thoracoepigastric region after an ultrasound-guided
      mammotome biopsy of a breast. In the histopathological examination the lesion was
      diagnosed as fibroadenoma. Regardless of the disease's etiology, it is
      recommended to carry out diagnostic examinations to exclude co-occurring breast
      cancer. 

PMID- 25960808
TI  - The aberrant overexpression of vimentin is linked to a more aggressive status in
      tumours of the gastrointestinal tract.
AB  - Vimentin is an intermediate filament protein normally expressed in cells of
      mesenchymal origin, e.g. myofibroblasts, chondrocytes, macrophages, and
      endothelial cells. The expression of vimentin, which has been thought of as the
      main mesenchymal marker, is also detected in tumour tissue. In tumours of the
      gastrointestinal tract vimentin expression is usually correlated with advanced
      stage of tumour, lymph node metastasis, and patient survival. 

PMID- 25960807
TI  - (13)CO2 breath tests in non-invasive hepatological diagnosis.
AB  - In liver diagnostics, a simple, non-invasive test with high sensitivity and
      specificity is permanently being sought in order to assess the degree of liver
      damage. In addition to liver biopsy, algorithms using blood parameters or
      elastometry are used in clinical practice. However, these methods do not provide
      information about the true liver reserve, so the liver breath test seem to be a
      promising diagnostic tool. The basis of this test depends on the ability of
      particular hepatocyte enzyme systems to metabolise a tested substance labelled
      with a stable carbon isotope. The kinetics of (13)CO2 elimination with expiratory
      air then permits quantitative assessment of the functional liver reserve and the
      degree of organ damage. In this paper the most commonly used tests, grouped
      according to the main metabolic pathways, are described. The usefulness of liver
      breath tests in specific clinical situations, both as a diagnostic and prognostic
      tool, is presented. 

PMID- 25960809
TI  - Non-dietary methods in the treatment of celiac disease.
AB  - This is a selective review of the literature concerning the methods of celiac
      disease treatment, which can be an alternative to a gluten-free diet. The most
      advanced studies are devoted to the larazotide acetate (AT-1001, human zonulin
      inhibitor) and prolyl-endopeptidases degrading toxic gluten peptides (ALV003, AN
      PEP). It is estimated that they will be registered within a few years. They will
      not become an alternative to the gluten-free diet but rather a supplement to it,
      which will enable patients to ease the nutritional restrictions. 

PMID- 25960810
TI  - Treatment of hypertriglyceridemia-induced acute pancreatitis with insulin.
AB  - INTRODUCTION: Hypertriglyceridaemia (HT)-induced pancreatitis rarely occurs
      unless triglyceride levels exceed 1000 mg/dl. Hypertriglyceridaemia over 1,000
      mg/dl can provoke acute pancreatitis (AP) and its persistence can worsen the
      clinical outcome. In contrast, a rapid decrease in triglyceride level is
      beneficial. Insulin-stimulated lipoprotein lipase is known to decrease serum
      triglyceride levels. However, their efficacy in HT-induced AP is not well
      documented. AIM: To present 12 cases of AP successfully treated by insulin
      administration. MATERIAL AND METHODS: Three hundred and forty-three cases of AP
      were diagnosed at our clinic between 2005 and 2012. Twelve (3.5%) of these cases
      were HT-induced AP. Twelve patients who suffered HT-induced AP are reported.
      Initial blood triglyceride levels were above 1000 mg/dl. Besides the usual
      treatment of AP, insulin was administered intravenously in continuous infusion.
      The patients' medical records were retrospectively evaluated in this study.
      RESULTS: Serum triglyceride levels decreased to < 500 mg/dl within 2-3 days. No
      complications of treatment were seen and good clinical outcome was observed.
      CONCLUSIONS: Our results are compatible with the literature. Insulin may be used
      safely and effectively in HT-induced AP therapy. Administration of insulin is
      efficient when used to reduce triglyceride levels in patients with HT-induced AP.

PMID- 25960811
TI  - Intestinal stoma in patients with colorectal cancer from the perspective of 20
      year period of clinical observation.
AB  - INTRODUCTION: Intestinal stoma is a procedure most often performed in patients
      with colorectal cancer. AIM: To identify the percentage of patients with
      colorectal cancer in which the intestinal stoma was performed. MATERIAL AND
      METHODS: We retrospectively analysed 443 patients treated during a 20-year period
      (1994-2013) due to colorectal cancer, in which the intestinal stoma was made
      during the first surgical intervention. RESULTS: In the second analysed decade, a
      significant decrease in the percentage of created stomas, definitive stomas in
      particular, was observed. Stomas were made significantly more often in patients
      with a tumour located in the rectum, the left half of the colon, and in patients
      undergoing urgent surgeries. An increased incidence of intestinal stomas was
      associated with a higher severity of illness and higher proportion of
      unresectable and non-radical procedures. The definitive stomas were significantly
      more often made in men and in patients with tumours located in the rectum,
      whereas temporary stomas were created significantly more often in patients
      undergoing urgent operations. CONCLUSIONS: In the last decade (2004-2013) the
      number of intestinal stomas in patients operated due to colorectal cancer was
      significantly reduced.

PMID- 25960812
TI  - Small intestinal bacterial overgrowth syndrome in children.
AB  - INTRODUCTION: Small intestinal bacterial overgrowth syndrome (SIBO) is defined as
      an increased number of nonpathogenic bacteria over 10(5) organisms in 1
      millilitre of small intestine content. The most common predisposing factors
      include, among others, gut motility disorders and chronic use of proton pump
      inhibitors. The results of recent studies indicate the importance of SIBO in
      gastrointestinal diseases. AIM: To assess the prevalence of SIBO in children with
      abdominal pain. MATERIAL AND METHODS: One hundred children (59 girls and 41 boys)
      aged from 4 to 17 years (mean age: 10.47 +/-3.73 years), hospitalised due to
      abdominal pain, were enrolled in the study. Hydrogen breath test (HBT) with
      lactulose was established among all patients. Expired air was analysed using a
      Gastrolyzer (Bedfont). RESULTS: The HBT result was positive in 63 (63%) children
      with abdominal pain; including 40 girls (67.8%) and 23 boys (56.1%). The test was
      positive in the group of 29 (46%) children aged under 10 years and in the group
      of 34 (54%) children aged over 10 years. Among the patients who reported for the
      control study 88% achieved a normalisation of HBT after treatment. CONCLUSIONS:
      The prevalence of positive HBT results in the group of patients with abdominal
      pain is over 60%. Small intestinal bacterial overgrowth syndrome should be
      considered as one of the causes of abdominal pain in children. The SIBO in
      children shows a good response to treatment.

PMID- 25960813
TI  - Surgery in Jehovah's Witnesses - our experience.
AB  - INTRODUCTION: Surgeons face a special challenge in treating Jehovah's Witnesses
      who refuse blood transfusion. AIM: To present our surgical experience with this
      group of patients operated on in our department. MATERIAL AND METHODS: A
      retrospective study of 16 unselected Jehovah's Witnesses patients was conducted
      between October 2004 and February 2012. We analysed gender, age, haemogram before
      and after surgery, types of surgery, postoperative complications and the need for
      blood transfusion, and/or other drugs stimulating erythrogenesis. RESULTS: Eighty
      one percent of patients were women; the average age of all patients was 57.3
      years. Mean haemoglobin level, preoperative, postoperative, and on the day of
      discharge from hospital, was 12.5 g/dl, 9.7 g/dl, and 9.29 g/dl, respectively.
      Over the same time period, mean red blood cell count was 4.53 mln/ul, 3.58
      mln/ul, and 3.37 mln/ul, respectively. Two out of 16 patients agreed to have
      blood transfusion. Drugs used for erythropoiesis stimulation included rEPO,
      ferrum, and folic acid. No surgical death was noted. CONCLUSIONS: We found that
      abdominal surgery was safe in our small group of Jehovah's Witness patients.
      However, all Jehovah's Witness patients should be fully informed about the type
      of procedure and possible consequences of blood transfusion refusal. Two of our
      patients agreed to blood transfusion in the face of risk of death.

PMID- 25960814
TI  - Elastography in pancreatic solid tumours diagnoses.
AB  - INTRODUCTION: Pancreatic solid tumour diagnoses remain a challenge for modern
      medicine. However, using endosonography together with elastography helps to
      examine the elasticity of tissues and therefore may allow definition of the
      nature of pancreatic tumours. AIM: To evaluate the usefulness of elastography
      with the strain ratio method and quantitative evaluation of pancreatic solid
      tumours. MATERIAL AND METHODS: A total of 54 patients with pancreatic solid
      tumours were treated with ultrasound endosonography with fine-needle aspiration
      biopsy. The control group contained 26 patients with normal pancreas. Pancreatic
      solid tumours and normal pancreas were analysed with elastography and elasticity
      evaluation of the interest area (A), reference (B), and the strain ratio factor
      (B/A). Postoperative histopathological or cytological examinations were the final
      diagnoses. Both postoperative and cytological diagnoses were compared with
      average elasticity parameters (A) and strain ratio factors (B/A). RESULTS:
      Average elasticity parameters (A) and the strain ratio factors (B/A) were: 0.025%
      (0.01-0.05%) for malignant process, and (B/A) 33.93 (18.23-75.45); (A) - 0.26%
      (0.14-0.35%), and (B/A) 5.35 (3.47-7.8) for inflammatory process; (A) 0.54% (0.35
      0.82%), and (B/A) 1.79 (1.02-2.05) for normal pancreatic tissue. CONCLUSIONS:
      Malignant tumours have higher tightness factor compared to inflammatory tumours
      and normal pancreatic tissue. Elasticity parameters reach the highest levels in
      normal pancreatic tissue, lower in inflammatory tumours, and the lowest in
      malignant tumours.

PMID- 25960815
TI  - Severe viral oesophagitis, pharyngitis, and stomatitis as antecedents of
      ileocecal Crohn's disease.
AB  - We present a 22-year-old male who developed a severe erosive oesophagitis
      extending to the pharynx and oral cavity without obvious risk factors. Endoscopic
      image suggested viral aetiology that could not be confirmed by routine
      serological diagnostics of infections with cytomegalovirus, Epstein-Barr virus,
      and Herpes simplex virus. The histopathological evaluation also gave no definite
      clues to the aetiology of the inflammation. Treatment with acyclovir was
      ineffective, but gancyclovir therapy caused spectacular clinical improvement and
      healing of erosions. Two months later the patient presented febrile diarrhoea
      that was a symptom of ileocecal Crohn's disease proven by endoscopy,
      enterography, and histopathology. It is the first report of severe viral
      oesophagitis preceding clinical manifestation of Crohn's disease. This
      observation warrants further study towards the viral aetiology of oral,
      pharyngeal, and oesophageal erosions, frequently associated with Crohn's disease.

PMID- 25960816
TI  - Autoimmune pancreatitis: a case of difficult diagnosis.
AB  - Autoimmune pancreatitis (AIP) is an insidious disease of non-specific
      symptomatology. To make correct diagnosis three different findings must
      correlate: radiological imaging, serological markers, and histology. This is not
      easy, and furthermore an incorrect diagnosis can lead to incorrect management and
      even patient death. We present our experience with a case of AIP in a young woman
      (34 years old) affected by different autoimmune pathologies with a history of
      abdominal pain. The diagnosis was made correlating histological findings and
      anamnestic data, although there were no radiological or serological findings.
      However, the management of this case was complicated by acute pancreatitis. In
      our case, we had only a histological sample and anamnestic data. So in these
      cases of positive history for autoimmune disorders and unclear clinical signs,
      AIP should be considered in differential diagnosis. 

PMID- 25960817
TI  - Acute acalculous cholecystitis in a 17-year-old girl with Epstein-Barr virus
      infection.
AB  - Acute cholecystitis is most frequently concomitant with cholelithiasis, whereas
      acute acalculous cholecystitis is usually of an infectious aetiology. Among the
      aetiological factors, Epstein-Barr virus (EBV) infection is also mentioned. The
      case of a 17-year-old girl is described, hospitalised in the Children's Clinical
      Hospital, Paediatric Clinic, at the Medical University in Lublin, due to fever,
      upper abdomen pain lasting for a week, and nausea for several days. Based on the
      diagnostic - laboratory tests performed and ultrasonographic examination, acute
      acalculous cholecystitis was diagnosed, taking course with elevated
      aminotransferase activity and features of cholestasis. Serological tests
      confirmed an acute infection with Epstein-Barr virus. After 2 weeks of
      hospitalisation, the patient, receiving conservative treatment, was discharged
      home in good condition. A follow-up examination performed 2 weeks later did not
      show deviation from normal. 

PMID- 25960818
TI  - Extraosseous, epidural cavernous hemangioma with back pain.
AB  - BACKGROUND: Cavernous malformations are characterized by enlarged vascular
      structures located in benign neural tissues within the cerebellum and spinal cord
      of the central nervous system. Cavernous hemangiomas (CHs) account for 5% to 12%
      of all spinal vascular malformations. CASE REPORT: We removed a hemorrhagic
      thoracic mass in a 40-year-old male patient who presented with progressive
      neurological deficits. CONCLUSIONS: We found it appropriate to present this case
      due to its rarity.

PMID- 25960819
TI  - Posterior Reversible Encephalopathy Syndrome (PRES): Restricted Diffusion does
      not Necessarily Mean Irreversibility.
AB  - BACKGROUND: Restricted diffusion is the second most common atypical presentation
      of PRES. This has a very important implication, as lesions with cytotoxic edema
      may progress to infarction. Several studies suggested the role of DWI in the
      prediction of development of infarctions in these cases. Other studies, however,
      suggested that PRES is reversible even with cytotoxic patterns. Our aim was to
      evaluate whether every restricted diffusion in PRES is reversible and what
      factors affect this reversibility. MATERIAL/METHODS: Thirty-six patients with
      acute neurological symptoms suggestive of PRES were included in our study.
      Inclusion criteria comprised imaging features of atypical PRES where DWI images
      and ADC maps show restricted diffusion. Patients were imaged with 0.2-T and 1.5-T
      machines. FLAIR images were evaluated for the severity of the disease and a
      FLAIR/DWI score was used. ADC values were selectively recorded from the areas of
      diffusion restriction. A follow-up MRI study was carried out in all patients
      after 2 weeks. Patients were classified according to reversibility into: Group 1
      (reversible PRES; 32 patients) and Group 2 (irreversible changes; 4 patients).
      The study was approved by the University's research ethics committee, which
      conforms to the declaration of Helsinki. RESULTS: The age and blood pressure did
      not vary significantly between both groups. The total number of regions involved
      and the FLAIR/DWI score did not vary significantly between both groups.
      Individual regions did not reveal any tendency for the development of
      irreversible lesions. Similarly, ADC values did not reveal any significant
      difference between both groups. CONCLUSIONS: PRES is completely reversible in the
      majority of patients, even with restricted diffusion. None of the variables under
      study could predict the reversibility of PRES lesions. It seems that this process
      is individual-dependent.

PMID- 25960820
TI  - Radiological illustration of spontaneous ovarian hyperstimulation syndrome.
AB  - BACKGROUND: The role of radiology is of utmost importance not only in diagnosing
      s-OHSS but also in ruling out other cystic ovarian diseases and to determine the
      underlying etiology and course of the disease. We presented a radiological
      algorithm for diagnosing the various causes of s-OHSS. CASE REPORT: A 26-year-old
      female, gravida one was referred to radiology department with history of lower
      abdominal pain, nausea and vomiting since 2 days which was gradual in onset and
      progression. The patient had no significant medical and surgical history.
      CONCLUSIONS: This article illustrates and emphasizes that diagnosis of s-OHSS and
      its etiology can be completely evaluated radiologically. Biochemical markers will
      confirm the radiological diagnosis.

PMID- 25960821
TI  - Complex Psychiatric Comorbidity of Treatment-Seeking Youth With Autism Spectrum
      Disorder and Anxiety Symptoms.
AB  - Anxiety disorders and other co-occurring psychiatric disorders significantly
      impact adaptive functioning for many children with autism spectrum disorder
      (ASD). This descriptive study examines the complexity of psychiatric comorbidity
      in treatment-seeking youth with ASD and anxiety symptoms. Forty-two parents of 8-
      to 14-year-old children with ASD and anxiety symptoms completed a structured
      psychiatric interview (K-SADS) and provided information about the child's past
      and current psychological functioning as part of a screening process to enter an
      anxiety intervention program. Overall, comorbidity was very complex, with
      children obtaining an average of 4 psychiatric diagnoses (including anxiety
      disorders) on a structured clinical interview (range = 0-9). Onset and course
      differed by psychiatric disorder. Complexity of comorbidity did not differ
      significantly by age, sex, or autism severity. Despite clinical significance of
      the symptoms reported, few children were currently (or ever) engaged in mental
      health treatment or group psychosocial intervention. Although the specificity of
      the current sample limits the generalizability of these results, findings suggest
      that treatment-seeking children with ASD and anxiety often present with
      additional psychiatric symptoms, which supports a transdiagnostic approach to
      research and intervention in this area. Accurate assessment of comorbidity may
      provide valuable information for families and clinicians regarding individualized
      treatment approaches.

PMID- 25960822
TI  - Structure-Directed Exciton Dynamics in Templated Molecular Nanorings.
AB  - Conjugated polymers with cyclic structures are interesting because their symmetry
      leads to unique electronic properties. Recent advances in Vernier templating now
      allow large shape-persistent fully conjugated porphyrin nanorings to be
      synthesized, exhibiting unique electronic properties. We examine the impact of
      different conformations on exciton delocalization and emission depolarization in
      a range of different porphyrin nanoring topologies with comparable spatial
      extent. Low photoluminescence anisotropy values are found to occur within the
      first few hundred femtoseconds after pulsed excitation, suggesting ultrafast
      delocalization of excitons across the nanoring structures. Molecular dynamics
      simulations show that further polarization memory loss is caused by out-of-plane
      distortions associated with twisting and bending of the templated nanoring
      topologies.

PMID- 25960824
TI  - Bioactive oleanane glycosides from Polyscias duplicata from the Madagascar dry
      forest.
AB  - As part of the International Cooperative Biodiversity Group (ICBG) program, in a
      search for antiproliferative compounds, an ethanol extract of Polyscias duplicata
      was investigated due to its antiproliferative activity against the A2780 human
      ovarian cell cancer line (IC50 6 ug/mL). Seven known oleanane glycosides, 3beta
      [(alpha-L-arabinopyranosyl)oxy]-16alpha-hydroxyolean-12-en-28-oic acid (1, IC50 8
      uM), 3beta-[(alpha-L-arabinopyranosyl)oxy]-16alpha,23-dihydroxyolean-12-en-18-oic
      acid (2, IC50 13 uM), 3beta-[(O-beta-D-glucopyranosyl-(t-->3)-alpha-L
      arabinopyranosyl)oxy]-16alpha-hydroxyolean-12-en-28-oic acid (3, IC50 7 uM),
      3beta-[(O-alpha-L-rhamnopyranosyl-(1-2)-alpha-L-arabinopyranosyl)oxy]-16alpha
      hydroxyolean-12-en-28-oic acid (4, IC50 2.8 uM), 3beta-[(O-beta-D-glucopyranosyl
      (l-->3)-alpha-L- arabinopyranosyl)oxy]-23-hydroxyolean-12-en-28-oic acid (5, IC50
      10 uM), beta-[(O-alpha-L-rhamnopyranosyl-(-1.2)-alpha-L-arabinopyranosyl)oxy]-23
      hydroxyolean-12-en-28-oic acid (6, IC50 3.4 uM), and 3beta-[(alpha-L
      arabinopyranosyl)oxy]-23-hydroxyolean-12-en-28-oic acid (7, IC50 3.4 uM) were
      isolated, and their structures determined using spectroscopic methods.

PMID- 25960823
TI  - 15N Hyperpolarization by Reversible Exchange Using SABRE-SHEATH.
AB  - NMR signal amplification by reversible exchange (SABRE) is a NMR
      hyperpolarization technique that enables nuclear spin polarization enhancement of
      molecules via concurrent chemical exchange of a target substrate and parahydrogen
      (the source of spin order) on an iridium catalyst. Recently, we demonstrated that
      conducting SABRE in microtesla fields provided by a magnetic shield enables up to
      10% 15N-polarization (Theis, T.; et al. J. Am. Chem. Soc.2015, 137, 1404).
      Hyperpolarization on 15N (and heteronuclei in general) may be advantageous
      because of the long-lived nature of the hyperpolarization on 15N relative to the
      short-lived hyperpolarization of protons conventionally hyperpolarized by SABRE,
      in addition to wider chemical shift dispersion and absence of background signal.
      Here we show that these unprecedented polarization levels enable 15N magnetic
      resonance imaging. We also present a theoretical model for the hyperpolarization
      transfer to heteronuclei, and detail key parameters that should be optimized for
      efficient 15N-hyperpolarization. The effects of parahydrogen pressure, flow rate,
      sample temperature, catalyst-to-substrate ratio, relaxation time (T1), and
      reversible oxygen quenching are studied on a test system of 15N-pyridine in
      methanol-d4. Moreover, we demonstrate the first proof-of-principle 13C
      hyperpolarization using this method. This simple hyperpolarization scheme only
      requires access to parahydrogen and a magnetic shield, and it provides large
      enough signal gains to enable one of the first 15N images (2 * 2 mm2 resolution).
      Importantly, this method enables hyperpolarization of molecular sites with NMR T1
      relaxation times suitable for biomedical imaging and spectroscopy.

PMID- 25960825
TI  - Management of Coronary Artery Calcium and Coronary CTA Findings.
AB  - Coronary artery calcium (CAC) testing and coronary computed tomography
      angiography (CTA) have significant data supporting their ability to identify
      coronary artery disease (CAD) and classify patient risk for atherosclerotic
      cardiovascular disease (ASCVD). Evidence regarding CAC use for screening has
      established an excellent prognosis in patients with no detectable CAC, and the
      ability to risk re-classify the majority of asymptomatic patients considered
      intermediate risk by traditional risk scores. While data regarding the ideal
      management of CAC findings are limited, evidence supports statin consideration in
      patients with CAC > 0 and individualized aspirin therapy accounting for CAD risk
      factors, CAC severity, and factors which increase a patient's risk of bleeding.
      In patients with stable or acute symptoms undergoing coronary CTA, a normal CTA
      predicts excellent prognosis, allowing reassurance and disposition without
      further testing. When CTA identifies nonobstructive CAD (<50 % stenosis),
      observational data support consideration of statin use/intensification in
      patients with extensive plaque (at least four coronary segments involved) and
      patients with high-risk plaque features. In patients with both nonobstructive and
      obstructive CAD, multiple studies have now demonstrated an ability of CTA to
      guide management and improve CAD risk factor control. Still, significant under
      treatment of cardiovascular risk factors and high-risk image findings remain,
      among concerns that CTA may increase invasive angiography and revascularization.
      To fully realize the impact of atherosclerosis imaging for ASCVD prevention,
      patient engagement in lifestyle changes and the modification of ASCVD risk
      factors remain the foundation of care. This review provides an overview of
      available data and recommendations in the management of CAC and CTA findings.

PMID- 25960826
TI  - Effects of docosahexaenoic supplementation and in vitro vitamin C on the
      oxidative and inflammatory neutrophil response to activation.
AB  - We studied the effects of diet supplementation with docosahexaenoic (DHA) and in
      vitro vitamin C (VitC) at physiological concentrations on oxidative and
      inflammatory neutrophil response to phorbol myristate acetate (PMA). Fifteen male
      footballers ingested a beverage enriched with DHA or a placebo for 8 weeks in a
      randomized double-blind study. Neutrophils were isolated from blood samples
      collected in basal conditions at the end of nutritional intervention. Neutrophils
      were cultured for 2 hours at 37 degrees C in (a) control media, (b) media with
      PMA, and (c) media with PMA + VitC. PMA induces neutrophil degranulation with
      increased extracellular myeloperoxidase and catalase activities, nitric oxide
      production, expression of the inflammatory genes cyclooxygenase-2, nuclear factor
      kappabeta, interleukin 8 and tumor necrosis factor alpha, and interleukin 6
      production. DHA diet supplementation boosts the exit of CAT from neutrophils but
      moderates the degranulation of myeloperoxidase granules induced by PMA. VitC
      facilitates azurophilic degranulation of neutrophils and increases gene
      expression of myeloperoxidase induced by PMA. VitC and DHA diet supplementation
      prevent PMA effects on inflammatory gene expression, although together they do
      not produce additional effects. DHA diet supplementation enhances antioxidant
      defences and anti-inflammatory neutrophil response to in vitro PMA activation.
      VitC facilitates neutrophil degranulation but prevents an inflammatory response
      to PMA. 

PMID- 25960827
TI  - Apigenin Attenuates Atherogenesis through Inducing Macrophage Apoptosis via
      Inhibition of AKT Ser473 Phosphorylation and Downregulation of Plasminogen
      Activator Inhibitor-2.
AB  - Macrophage survival is believed to be a contributing factor in the development of
      early atherosclerotic lesions. Dysregulated apoptosis of macrophages is involved
      in the inflammatory process of atherogenesis. Apigenin is a flavonoid that
      possesses various clinically relevant properties such as anti-inflammatory,
      antiplatelet, and antitumor activities. Here we showed that apigenin attenuated
      atherogenesis in apoE (-/-) mice in an in vivo test. In vitro experiments
      suggested that apigenin induced apoptosis of oxidized low density lipoprotein-
      (OxLDL-) loaded murine peritoneal macrophages (MPMs). Proteomic analysis showed
      that apigenin reduced the expression of plasminogen activator inhibitor 2 (PAI
      2). PAI-2 has antiapoptotic effects in OxLDL-loaded MPMs. Enhancing PAI-2
      expression significantly reduced the proapoptosis effects of apigenin. Molecular
      docking assay with AutoDock software predicted that residue Ser473 of Akt1 is a
      potential binding site for apigenin. Lentiviral-mediated overexpression of Akt1
      wild type weakened the proapoptosis effect of apigenin in OxLDL-loaded MPMs.
      Collectively, apigenin executes its anti-atherogenic effects through inducing
      OxLDL-loaded MPMs apoptosis. The proapoptotic effects of apigenin were at least
      partly attributed to downregulation of PAI-2 through suppressing phosphorylation
      of AKT at Ser473. 

PMID- 25960829
TI  - Understanding the concept of brain death in the middle East.

PMID- 25960828
TI  - Targeting TRAF3 Downstream Signaling Pathways in B cell Neoplasms.
AB  - B cell neoplasms comprise >50% of blood cancers. However, many types of B cell
      malignancies remain incurable. Identification and validation of novel genetic
      risk factors and oncogenic signaling pathways are imperative for the development
      of new therapeutic strategies. We and others recently identified TRAF3, a
      cytoplasmic adaptor protein, as a novel tumor suppressor in B lymphocytes. We
      found that TRAF3 inactivation results in prolonged survival of mature B cells,
      which eventually leads to spontaneous development of B lymphomas in mice.
      Corroborating our findings, TRAF3 deletions and inactivating mutations frequently
      occur in human B cell chronic lymphocytic leukemia, splenic marginal zone
      lymphoma, mantle cell lymphoma, multiple myeloma, Waldenstrom's
      macroglobulinemia, and Hodgkin lymphoma. In this context, we have been
      investigating TRAF3 signaling mechanisms in B cells, and are developing new
      therapeutic strategies to target TRAF3 downstream signaling pathways in B cell
      neoplasms. Here we discuss our new translational data that demonstrate the
      therapeutic potential of targeting TRAF3 downstream signaling pathways in B
      lymphoma and multiple myeloma.

PMID- 25960830
TI  - Khat use: history and heart failure.
AB  - Recent reports suggest that 20 million people worldwide are regularly using khat
      as a stimulant, even though the habit of chewing khat is known to cause serious
      health issues. Historical evidence suggests khat use has existed since the 13th
      century in Ethiopia and the southwestern Arabian regions even before the
      cultivation and use of coffee. In the past three decades, its availability and
      use spread all over the world including the United States and Europe. Most of the
      consumers in the Western world are immigrant groups from Eastern Africa or the
      Middle East. The global transport and availability of khat has been enhanced by
      the development of synthetic forms of its active component. The World Health
      Organization considers khat a drug of abuse since it causes a range of health
      problems. However, it remains lawful in some countries. Khat use has long been a
      part of Yemeni culture and is used in virtually every social occasion. The main
      component of khat is cathinone, which is structurally and functionally similar to
      amphetamine and cocaine. Several studies have demonstrated that khat chewing has
      unfavorable cardiovascular effects. The effect on the myocardium could be
      explained by its effect on the heart rate, blood pressure, its vasomotor effect
      on the coronary vessels, and its amphetamine-like effects. However, its direct
      effect on the myocardium needs further elaboration. To date, there are few
      articles that contribute death among khat chewers to khat-induced heart failure.
      Further studies are needed to address the risk factors in khat chewers that may
      explain khat-induced cardiotoxicity, cardiomyopathy, and heart failure. 

PMID- 25960831
TI  - Switching to multiple daily insulin injections in children and adolescents with
      type 1 diabetes: revisiting benefits from oman.
AB  - OBJECTIVES: Optimal glycemic control is an important goal in the management of
      type 1 diabetes mellitus (T1DM). Although the use of multiple daily injections
      (MDI) is a common regimen worldwide, its use is not yet universal in many
      countries. Our aim was to evaluate the effects of switching from a twice daily
      (BID) to a MDI insulin regimen in children and adolescents with T1DM in order to
      revisit its benefits in the Omani population. METHODS: We conducted a
      retrospective cohort study of children and adolescents with T1DM at Sultan Qaboos
      University Hospital, Muscat, Oman, between January 2007 and June 2013. Patients
      using the BID regimen for more than six months who were then switched to MDI were
      included in the analysis. We compared glycated hemoglobin levels (HbA1c) before
      and after the regimen change. RESULTS: Fifty-three children were eligible for the
      study. Ten patients were excluded for various reasons. The remaining 43 patients
      were 58% male and 42% female, with a mean age of 9.4+/-3.7 years. There was
      significant decrease in the overall mean HbA1c level from baseline (10.0)
      compared to three months after switching to MDI (9.5); p=0.023. Nevertheless, the
      improvement was not significant in the subsequent follow-up visits at six and
      nine months. The reduction in HbA1c values was observed mainly in children five
      to 11 years. CONCLUSIONS: Switching from a BID to MDI insulin regimen has
      favorable effects on the overall control of T1DM in children and adolescents, as
      assessed by HbA1c levels. In addition, this regimen has been proved to be safe
      and well tolerated by patients.

PMID- 25960832
TI  - White coat hypertension and masked hypertension among omani patients attending a
      tertiary hospital for ambulatory blood pressure monitoring.
AB  - OBJECTIVES: Our study aimed to estimate the rate of white coat hypertension (WCH)
      and effect, and masked hypertension in patients attending a tertiary care
      hospital for 24 hour ambulatory blood pressure monitoring (24-h ABPM). METHODS: A
      total of 231 adult patients were referred to the Department of Clinical
      Physiology at Sultan Qaboos University Hospital, Muscat, for ABPM, between
      January 2010 and June 2012. The following data were gathered and analyzed:
      demographic data, clinic blood pressure (BP) measurements, and 24-h BP profile
      from ABPM. Thirty-two patients were excluded and the final analysis included 199
      patients. RESULTS: There were 105 (52.8%) women and 94 (47.2%) men studied. The
      mean age of patients was 46+/-15 years and most patients were overweight with a
      mean BMI of 29.6+/-5kg/m(2). Around half of patients (53.8%) were on one or more
      antihypertensive medications. WCH was found in 10.6% and white coat effect was
      found in 16% of patients. The majority of patients (57%) with WCH were aged 40
      years or above. Masked hypertension was present in 6% of patients and masked
      uncontrolled hypertension in 8.5% of patients. CONCLUSIONS: Our study showed that
      WCH and effect, and masked hypertension are common in hypertensive patients.
      Identifying these patients will have an impact on their management. However, the
      results of the study should be interpreted within the context of its limitations.
      Prospective randomized community and hospital-based studies should be conducted
      to estimate the true prevalence in the general population as well as in
      hypertensive patients.

PMID- 25960833
TI  - Trends of sickness certifications in primary health care in muscat, sultanate of
      oman.
AB  - OBJECTIVES: Sickness certification (SC) is common practice in primary health care
      with proven implications on the health system. To assess the rate of sickness
      certifications in the Bowsher province and describe related demographic,
      occupational and medical factors. METHODS: Our retrospective, cross-sectional
      study retrieved data for all consultations, with patients aged six to 65 years
      old, which ended with SC. The data from four primary health care centers in the
      Bowsher provice were collected during 2011 using the electronic medical record
      system. Collected data included patient demographics, occupation, date issued,
      duration of sickness certification, recorded vital signs, and clinical diagnosis.
      Suitable rates were calculated as percentages and important differences were
      compared using the chi-square test. RESULTS: The total number of consultation
      visits for the targeted population was 189,275. Of these 26,096 consultations
      resulted in SC to a total of 15,758 patients. The overall rate of SC was 13.8 per
      100 consultation-years (confidence interval (CI): 13.6-14). SC rates in males
      were significantly higher than females (17 and 11 per 100 consultations/year,
      respectively). Patients aged 19-29 years old had the highest rate of SC (18.6/100
      consultations/year). School students aged six to 18 years made up 28% of
      patients, and 24% and 22% of patients were working in the private and public
      sectors, respectively. No vital signs record was found for 30% of SC visits. The
      highest rate of SC was in October (17%) and the lowest was in August (9%). Acute
      respiratory infections were the most frequent diagnoses (31%) resulting in
      certifications. The rate of SC issued for Omanis and non-Omanis was 14 and 9 per
      100 consultations per year, respectively. CONCLUSION: Sickness certification is a
      burden on primary health care in the studied health centers with approximately
      one in seven consultations ending with SC issued. More investigations are needed
      to identify determinates of high sickness absence. Robust guidelines are
      important to regulate the number of sickness certificates issued.

PMID- 25960834
TI  - The metabolic syndrome and inflammation: ?role of insulin resistance and
      increased adiposity.
AB  - OBJECTIVES: We sought to determine the role of obesity and insulin resistance
      (IR) in the pathogenesis of inflammation in metabolic syndrome (MetS). METHODS:
      Our study included 100 patients with MetS and 100 age and gender matched control
      patients who attended a tertiary care laboratory in Rawalpindi, Pakistan.
      Anthropometric data was obtained including height and weight to calculate body
      mass index. A record of patient's blood pressure (BP), waist circumference (WC)
      and hip circumference (HC) was made. Biochemical analysis included measurements
      of fasting glucose, triglycerides (TG), high-density lipoprotein cholesterol (HDL
      c), insulin, and high-sensitivity C reactive protein (hsCRP). IR was determined
      by the homeostasis mode assessment insulin resistance (HOMA-IR) method. RESULTS:
      The levels of hs-CRP were found to be elevated in all patients with MetS where it
      correlated significantly with all its components including measures of obesity,
      fasting insulin and glucose levels, IR, TG and HDL-c. However, on linear
      regression analysis only WC, fasting insulin, and HOMA-IR remained significantly
      correlated with hs-CRP. CONCLUSION: MetS is a condition characterized by chronic
      low-grade inflammation, which arises because of increased abdominal adiposity and
      IR. Large multicenter studies are needed to gain insight into its pathogenesis
      and derive treatment strategies.

PMID- 25960835
TI  - Microbial air quality and bacterial surface contamination in ambulances during
      patient services.
AB  - OBJECTIVES: We sought to assess microbial air quality and bacterial surface
      contamination on medical instruments and the surrounding areas among 30 ambulance
      runs during service. METHODS: We performed a cross-sectional study of 106 air
      samples collected from 30 ambulances before patient services and 212 air samples
      collected during patient services to assess the bacterial and fungal counts at
      the two time points. Additionally, 226 surface swab samples were collected from
      medical instrument surfaces and the surrounding areas before and after ambulance
      runs. Groups or genus of isolated bacteria and fungi were preliminarily
      identified by Gram's stain and lactophenol cotton blue. Data were analyzed using
      descriptive statistics, t-test, and Pearson's correlation coefficient with a p
      value of less than 0.050 considered significant. RESULTS: The mean and standard
      deviation of bacterial and fungal counts at the start of ambulance runs were
      318+/-485cfu/m(3) and 522+/-581cfu/m(3), respectively. Bacterial counts during
      patient services were 468+/-607cfu/m(3) and fungal counts were 656+/-612cfu/m(3).
      Mean bacterial and fungal counts during patient services were significantly
      higher than those at the start of ambulance runs, p=0.005 and p=0.030,
      respectively. For surface contamination, the overall bacterial counts before and
      after patient services were 0.8+/-0.7cfu/cm(2) and 1.3+/-1.1cfu/cm(2),
      respectively (p<0.001). The predominant isolated bacteria and fungi were
      Staphylococcus spp. and Aspergillus spp., respectively. Additionally, there was a
      significantly positive correlation between bacterial (r=0.3, p<0.010) and fungal
      counts (r=0.2, p=0.020) in air samples and bacterial counts on medical
      instruments and allocated areas. CONCLUSIONS: This study revealed high microbial
      contamination (bacterial and fungal) in ambulance air during services and higher
      bacterial contamination on medical instrument surfaces and allocated areas after
      ambulance services compared to the start of ambulance runs. Additionally,
      bacterial and fungal counts in ambulance air showed a significantly positive
      correlation with the bacterial surface contamination on medical instruments and
      allocated areas. Further studies should be conducted to determine the optimal
      intervention to reduce microbial contamination in the ambulance environment.

PMID- 25960836
TI  - Rituximab leads to long remissions in patients with chronic immune
      thrombocytopenia.
AB  - OBJECTIVES: To assess the response rate and duration of response in patients with
      chronic immune thrombocytopenia (ITP) receiving rituximab. METHODS: We
      retrospectively analyzed 32 consecutive patients with chronic ITP who were
      treated in two tertiary centers in Oman. Response assessment was based on the
      American Society of Hematology criteria. RESULTS: Nineteen patients (59%) had an
      initial response. However, six of the 19 patients lost their response leaving 13
      patients with long-lasting remissions. The median age at diagnosis was 25 years
      (range 14-58). The median time from diagnosis to rituximab therapy was 21 months.
      The median follow-up after starting rituximab was 26 months. The overall
      cumulative response rate was 59% (complete response 44%, partial response 15%)
      and the median time to respond was 30 days with a response rate of 44% at four
      weeks. In all responders, the cumulative rate of loss of response was 32% with a
      median time to lose response of 54 months. CONCLUSIONS: The use of rituximab in
      ITP achieves high response rate and long remission duration. Our study was
      limited by the small sample size and further larger prospective studies are
      recommended.

PMID- 25960837
TI  - Vitamin D Deficiency in Patients with Irritable Bowel Syndrome: Does it Exist?
AB  - OBJECTIVES: Vitamin D has been found to be strongly associated with many systemic
      disorders. There has been an augmented interest within the medical community in
      vitamin D, especially its deficiency, in various systemic disorders. Although the
      role of vitamin D deficiency in irritable bowel syndrome (IBS) has not yet been
      established, studies are underway to clearly establish its role in the disease.
      The objective of our study was to elucidate and establish the role of vitamin D
      deficiency in IBS patients compared to a healthy control group. METHODS: This
      study is a comparative case control study of vitamin D deficiency in patients
      with IBS diagnosed with ROME 3 criteria of classification (the third ROME
      foundation classification) to an age and gender matched healthy control group.
      The vitamin D level was measured in both cohorts for comparison and the results
      interpreted statistically. Sixty patients with IBS and 100 healthy individuals
      were included as test and control groups, respectively, in the study. The mean
      serum vitamin D level (nmol/L) of IBS patients was compared to the control group.
      RESULTS: Vitamin D deficiency was detected in 49 patients (82%) in the IBS group
      and 31 patients (31%) in the control group. There was a statistically significant
      difference in the mean vitamin D level (p=0.025) between the IBS group and
      control group. CONCLUSIONS: Our study shows that vitamin D deficiency is highly
      prevalent in patients with IBS and these results seem to have therapeutic
      implications. Vitamin D supplementation could play a therapeutic role in the
      control of IBS.

PMID- 25960838
TI  - A retrospective analysis of 334 cases of hemoptysis treated by bronchial artery
      embolization.
AB  - OBJECTIVES: To analyze the safety and efficacy of bronchial artery embolization
      (BAE) in the management of hemoptysis. METHODS: We conducted a retrospective
      study of 334 patients who had undergone BAE for hemoptysis from January 2007 to
      July 2013. Our study included 255 (76.3%) males and 79 (23.7%) females with an
      age range from five to 81 years old. All relevant arteries were evaluated but
      only those arteries that showed hypertrophy and significant blush were targeted.
      Polyvinyl alcohol (PVA) was used in all patients and gel foam was used in
      combination with PVA where there was significant shunting. RESULTS: Mild
      hemoptysis was seen in 70 patients, moderate in 195 patients, and severe in 69
      patients. On imaging, right side disease was seen in 101 patients, left side
      involvement in 59 patients, and bilateral involvement in 174 patients. Post
      tubercular changes were the predominant pathology seen in 248 patients. Among 334
      patients (386 procedures), 42 patients underwent the procedure twice and five
      patients underwent the procedure thrice. A total of 485 arteries were attempted
      of which 440 arteries were successfully embolized. Right intercosto-bronchial was
      the most common culprit artery present in 157 patients, followed by common
      bronchial (n=97), left bronchial (n=55), and right bronchial (n=45). We embolized
      a maximum of four arteries in one session. Immediate complications such as
      dissection and rupture occurred in only nine sessions (2.3%). Twenty-five
      procedures (6.5%) were repeated within two months, which were due to technical or
      clinical failure and 27 procedures (7%) were repeated after two months.
      CONCLUSIONS: BAE is a safe and effective procedure with a negligible complication
      rate. Our approach of targeting hypertrophied arteries was effective.

PMID- 25960839
TI  - A Novel Mutation Causing 17-beta-Hydroxysteroid Dehydrogenase Type 3 Deficiency
      in an Omani Child: First Case Report and Review of Literature.
AB  - This is the first case report in Oman and the Gulf region of a 17-beta
      hydroxysteroid dehydrogenase type 3 (17-beta-HSD3) deficiency with a novel
      mutation in the HSD17B3 gene that has not been previously described in the
      medical literature. An Omani child was diagnosed with 17-beta-HSD3 deficiency and
      was followed up for 11 years at the Pediatric Endocrinology Clinic, Royal
      Hospital, Oman. He presented at the age of six weeks with ambiguous genitalia,
      stretched penile and bilateral undescended testes. Ultrasound showed no evidence
      of any uterine or ovarian structures with oval shaped solid structures in both
      inguinal regions that were confirmed by histology to be testicular tissues with
      immature seminiferous tubules only. The diagnosis was made by demonstrating low
      serum testosterone and high androstenedione, estrone, and
      androstenedione:testosterone ratio. Karyotyping confirmed 46,XY and the infant
      was raised as male. Testosterone injections (25mg once monthly) were given at two
      and six months and then three months before his surgeries at five and seven years
      of age when he underwent multiple operations for orchidopexy and hypospadias
      correction. At the age of 10 years he developed bilateral gynecomastia (stage 4).
      Laboratory investigations showed raised follicle-stimulating hormone, luteinizing
      hormone, androstenedione, and estrone with low-normal testosterone and low
      androstendiol glucurunide. Testosterone injections (50mg once monthly for six
      months) were given that resulted in significant reduction in his gynecomastia.
      Molecular analysis revealed a previously unreported homozygous variant in exon
      eight of the HSD17B3 gene (NM_000197.1:c.576G>A.Trp192*). This variant creates a
      premature stop codon, which is very likely to result in a truncated protein or
      loss of protein production. This is the first report in the medical literature of
      this novel HSD17B3 gene mutation. A literature review was conducted to identify
      the previous studies related to this disorder. 

PMID- 25960840
TI  - Delayed transient post-traumatic quadriplegia.
AB  - Transient neurological deficit following cervical trauma have been reported
      following sports injuries, and has been referred to as cervical cord neurapraxia.
      The so-called "whiplash injuries" following minor motor vehicle collisions
      usually do not produce any neurological deficit. Here we report the case of a
      whiplash type of injury presenting with a delayed onset neurological deficit,
      which was followed by rapid and complete recovery. The patient, an otherwise
      healthy 34-year-old male, attended the emergency department of Sultan Qaboos
      University Hospital following a rear-end motor vehicle collision. We present
      images showing degenerative disc disease causing spinal canal narrowing and mild
      cord compression in the patient, but no spinal instability. Differential
      diagnoses are also discussed. 

PMID- 25960841
TI  - Novel mutation in wolcott-rallison syndrome with variable expression in two omani
      siblings.
AB  - Wolcott-Rallison syndrome (WRS) is an autosomal recessive disease, characterized
      by neonatal or early-onset non-autoimmune insulin-dependent diabetes. WRS,
      although rare, is recognized to be the most frequent cause of neonatal-onset
      diabetes. The majority of reported patients are from consanguineous families.
      Several mutations with variable expression of the syndrome are reported. Here we
      describe a six-year-old boy with WRS who was evaluated at Sultan Qaboos
      University Hospital and was found to have a novel homozygous nonsense mutation in
      the EIF2AK3 gene. His younger sister also had WRS but with milder expression. The
      mutation exhibited different clinical characteristics in the siblings proving
      that WRS patients phenotypic variability correlates poorly to genotype. This is
      the first case report of two Omani children with WRS and a report of a novel
      mutation. 

PMID- 25960842
TI  - Traumatic asphyxia with diaphragmatic injury: ?a case report.
AB  - Traumatic asphyxia, or Perthe's syndrome, is a rare clinical syndrome
      characterized by cervicofacial cyanosis, petechiae, subconjunctival hemorrhage,
      neurological symptoms, and thoracic injury. It affects both adults and children
      after blunt chest traumas. The diagnosis of this condition is based mainly on the
      specific clinical signs, which should immediately bring to mind the severity of
      the trauma, the various probable types of pulmonary injuries, and the need for
      screening and careful assessment of other organs that might also be injured. In
      this report, we describe the case of a 39-year-old male who developed traumatic
      asphyxia after severe blunt chest trauma during his work at a construction site.
      The patient had multiple injuries to the chest, abdomen, head and neck, which
      were treated conservatively. An associated diaphragmatic injury was successfully
      treated by video-assisted thoracic surgery. This patient is one of five patients
      who were admitted to Saqr Hospital in the United Arab Emirates, diagnosed with
      traumatic asphyxia, and treated by mechanical ventilator, supportive measures,
      and fiberoptic bronchoscopy, for both diagnostic and therapeutic indications, in
      our unit in the period between July 2006 and June 2013. As traumatic asphyxia is
      a systemic injury, careful assessment of the patient and looking for other
      injuries is mandatory. Treatment usually involves supportive measures to the
      affected organs, but surgical intervention may sometimes prove to be an important
      part of the treatment. Bronchoscopy should be performed for diagnostic and
      therapeutic reasons because of the associated pulmonary and possible
      tracheobronchial injuries. 

PMID- 25960843
TI  - Abdominal pain in a young man.

PMID- 25960844
TI  - Effectiveness of group training based on acceptance and commitment therapy on
      anxiety and depression of women with breast cancer.
AB  - BACKGROUND: Breast cancer is the most common cancer in women that as a sudden
      event has profound effects on all aspects of patients' lives. Psychosocial
      interventions may play important roles in reducing anxiety and depression among
      breast-cancer survivors. Therefore, group training based on acceptance and
      commitment therapy may help women to cope better with their condition, and
      decrease their anxiety and depression. METHODS: In a quasi-experimental study, 30
      patients with breast cancer were selected by convenience sampling method and
      randomly assigned to 2 experimental and control groups. The experimental group
      attended acceptance and commitment training classes for 8 weeks continuously
      (each class lasting 90 minutes). Participants in both the experimental and
      control groups completed Beck Anxiety Inventory (BAI) and Beck Depression
      Inventory (BHI-II) as a pretest and posttest. Analysis of Covariance was used as
      the statistical method. RESULTS: In acceptance and commitment group training,
      anxiety and depression significantly decreased (p<0/05). These changes were not
      observed in the control group. CONCLUSION: The results showed that group training
      based on acceptance and commitment therapy is an effective method in reducing
      anxiety and depression. Hence psychological interventions can be used to reduce
      psychological difficulties of women with breast cancer.

PMID- 25960845
TI  - National health guidelines in I.R of iran, an innovative approach for developing
      countries.
AB  - BACKGROUND: Guidelines have produced and used in complex environment of health
      care system with its ethical, economical, legal and other aspects; that should be
      taken into account in any country. Modifying the format and content of guidelines
      might facilitate their usage and lead to improved quality of care and cost
      containment. We have produced this tool for explained above purpose. METHODS: A
      coordinating national team has settled at the office of minster of health and
      medical education, supported by a guideline review committee. An innovative and
      appropriate approach for adapting national health guidelines has consisted of
      eight steps, have defined For preparing the draft of each guideline a technical
      team which, including main author, her/his co-workers have nominated. The authors
      of each topic have systematically searched databases of the proposed Twenty-two
      International Sites, and then have selected at least five sources of them that
      were more relevant. The final recommendations have proposed by agreement of
      technical team and Guideline Review Committee. RESULTS: In less than 5 months,
      more than 500 authors in whole country have selected to prepare guidelines and,
      approximately 150 guidelines have provided in three volumes of the published and
      distributed book. Each guideline had a national ID number, constant forever; all
      topics should be reviewed every 3-5 years. CONCLUSION: National health
      guideline(s) would be essential means for policy making in health system and
      increased the cost containment and quality of care. Ministry of Health and
      Medical Education should provide and distribute the guidelines based on its
      accountability to legal responsibility.

PMID- 25960846
TI  - A Comparison of 5-HT3 Receptor Antagonist and Metoclopramide in the Patients
      Receiving Chemotherapeutic Regimens Including CMF, CAF and CHOP.
AB  - BACKGROUND: Chemotherapy- induced nausea and vomiting (CINV) occur frequently
      causing problems with an unacceptably high incidence that significantly affect
      patients' daily functioning and health-related quality of life. The present study
      was aimed to compare acute CINV for granisetron as 5-HT3 receptor antagonist and
      metoclopramide in the patients receiving chemotherapeutic regimens including
      cyclophosphamide and adriamycin. An attempt is made to examine whether it is
      possible to successfully replace granisetron with metoclopramide in control of
      acute CINV. METHODS: A total of 137 patients with breast cancer (78.8%) and
      lymphoma (17.5%) from two oncology departments in the first course of
      chemotherapy were enrolled. They received granisetron 3mg/IV and dexamethasone
      8mg for the first referring and in the second referring metoclopramid 30mg/IV and
      dexamethasone 8mg/IV thirty minutes before chemotherapy and metoclopramide
      20mg/IV during chemotherapy. The patients recorded the incidence of chemotherapy
      induced nausea and vomiting (CINV) and other side effects including headache,
      extra pyramidal manifestations and delayed nausea. RESULTS: Median age of studied
      patients was 49+/-15 year. The patients who received granisetron and
      dexamethasone had less acute nausea (during the first 24 hours after
      chemotherapy) than those who received metoclopramide. Also our study showed that
      controlled CINV episodes in patients who received CMF regimen were better than
      the regimen including adriamycin (CAF, CHOP) into both granisetron (p=0.06) and
      metoclopramid (p=0.04). The most common adverse event related to these drugs was
      extra pyramidal manifestations for 16 and 10 patients who had received
      granisetron and metoclopramide respectively. While the number of the patients who
      had sever delayed CINV (2-7 days after chemotherapy) episodes with granisetron (7
      cases) was lower than those who took metoclopramide drug (14 cases). The number
      of patients who experienced extrapyramidal manifestations in metoclopramide group
      was lower than granisetron group. CONCLUSION: There were not any significant
      clinically serious adverse events in any patients undergoing chemotherapy due to
      cancer. Thus, the safety profiles of granisetron and metoclopramide were
      comparable in this study. The patients who were treated with cyclophosphamide,
      and adriamycin, the efficacy of dexamethasone and metoclopramide in controlling
      acute nausea and vomiting nearly equaled to those of granisetron. Thus the
      present study supports the use of metoclopramide due to its lower cost and nearly
      the same efficacy and safety compared to granisetron in CMF regimen.

PMID- 25960847
TI  - Transhiatal Esophagectomy without Mediastinal Manipulation for Lower Third
      Esophageal and Cardial Cancers: The First Experience of a New Technique.
AB  - BACKGROUND: Considering the poor survival rate of patients with esophageal
      cancers, mainly due to the disease effects and surgical co morbidities, we have
      aimed to introduce a new method of Transhiatal Esophagectomy (THE) without
      mediastinal manipulation for lower third esophageal and cardial cancers. It has
      suggested that using this technique would decrease mentioned complications.
      METHODS: In this prospective study, patients with esophageal cancer who referred
      for surgical treatment have enrolled and undergone to new method of THE, without
      mediastinal manipulation. Pre and post-operative morbidities as well as the
      duration of procedure, duration of hospital and ICU stay have recorded. All
      patients have followed up or 4-40 months. RESULTS: In this study 53 patients with
      mean age of 55.2+/-10.3 years have undergone esophagectomy, and then in 50 of
      them the new method has performed. Median operative time and volume of blood loss
      was 120 minutes and 130 ml, respectively. Median duration of hospital and ICU
      stay was 7 and 1 day, respectively. There were no Pre-operative mortalities,
      arrhythmia, hemodynamic instability and mediastinal vessels injury. The most
      common co morbidities have related to our new method were mediastinal pleura
      injury, anastomotic leaks and anastomotic narrowing with 20%, 16% and 10%
      reported rate, respectively. CONCLUSION: The findings of current study have
      indicated that transhiatal esophagectomy without mediastinal manipulation, has
      represented a safe and effective method for treatment of lower third esophageal
      and cardial cancers due to its potential advantages of decreased blood loss,
      being a less traumatic procedure, minimal cardiopulmonary complications and low
      rate of hospital mortality.

PMID- 25960848
TI  - Cholorambucil versus Cholorambucil Plus Prednisolone as First-Line Therapy of
      Chronic Lymphocytic Leukemia in West of Iran.
AB  - BACKGROUND: Chronic lymphocytic leukemia (CLL) has been the most common type of
      leukemia in adults worldwide, and then more common in the elderly, markedly more
      common in patients over the age of 65 years. METHODS: Seventy patients with CLL
      have referred to Clinic of Hematology-Oncology, Kermanshah, Iran, between Jan
      2000 and Jun 2014. We have analyzed age, sex, survival, kind of chemotherapy and
      type of response in all of the patients with chronic lymphocytic leukemia.
      Survival curves of complete response patients have compared with partial
      response, by log-rank test using the Prism 5 GraphPad Software for the five-year
      period with two years follow up. RESULTS: The mean age of patients was 61.57+/
      8.88 years that 55.7% were males. Between the 70 patients, 40 patients (57.1%)
      have started treatment with chlorambucil and 30 patients (42.9%) with
      chlorambucil plus prednisolone. Among the forty patients that have treated with
      chlorambucil, overall response rate was 95% that 9 patients (22.5%) had complete
      response. Among the 30 patients that have treated with chlorambucil plus
      prednisolone, overall response rate was 96%, that 9 patients (30%) had complete
      response after six months of treatment. The mean of five-year overall survival
      for treated patients with chlorambucil and chlorambucil plus prednisolone in the
      first-line of therapy was 38.5 and 40.5 months, respectively. CONCLUSION:
      Combination of prednisolon to chlorambucil has increased survival rate in the
      patients more than mono-therapy with chlorambucil and also the complete response
      rate to chlorambucil in West of Iran was better than other areas of world.

PMID- 25960849
TI  - The Relationship between -2548 G/A Leptin Gene Polymorphism and Risk of Breast
      Cancer and Serum Leptin Levels in Ahvazian Women.
AB  - BACKGROUND: Potential association of leptin (LEP) gene polymorphisms has been
      suggested in the processes leading to breast cancer initiation and progression.
      We investigated whether genetic variations in the LEP -2548G/A gene are
      associated with risk of breast cancer. METHODS: This case-control study consisted
      of 100 breast cancer cases and 100 control subjects without breast cancer that
      matched for age and body mass index (BMI). Genotyping of LEP -2548G/A
      polymorphism was performed by polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) assay. Serum leptin level was determined by ELISA
      in all study subjects. RESULTS: The genotype distributions (AA, AG, and GG) were
      36, 55, and 9% in breast cancer cases and 52, 45, and 3% in control group,
      respectively. The frequency of LEP -2548 GG genotype was significantly elevated
      in breast cancer cases as compared to controls (chi2=6.90, p=0.032). Similar
      difference was also found in allele frequencies between two groups (chi2=5.65,
      p=0.017). A markedly increase risk of breast cancer was associated with the LEP 
      2548GG genotype when compared to the LEP -2548 AA genotype (OR=4.33, 95% CI=1.09
      17.22). In addition, postmenopausal women who bear at least one LEP -2548 G
      allele were at a markedly increased risk of breast cancer after adjusting for age
      and BMI confounders (OR=12.24, 95% CI=1.13-131.73). CONCLUSION: The LEP -2548 G/A
      polymorphism is associated with markedly increased risk of breast cancer
      especially in postmenopausal Ahvazian women and supported the hypothesis that
      leptin is involved in breast cancer.

PMID- 25960851
TI  - Application of texture analysis method for classification of benign and malignant
      thyroid nodules in ultrasound images.
AB  - BACKGROUND: The aim of this study was to evaluate computer aided diagnosis (CAD)
      system with texture analysis (TA) to improve radiologists' accuracy in
      identification of thyroid nodules as malignant or benign. METHODS: A total of 70
      cases (26 benign and 44 malignant) were analyzed in this study. We extracted up
      to 270 statistical texture features as a descriptor for each selected region of
      interests (ROIs) in three normalization schemes (default, 3s and 1%-99%). Then
      features by the lowest probability of classification error and average
      correlation coefficients (POE+ACC), and Fisher coefficient (Fisher) eliminated to
      10 best and most effective features. These features were analyzed under standard
      and nonstandard states. For TA of the thyroid nodules, Principle Component
      Analysis (PCA), Linear Discriminant Analysis (LDA) and Non-Linear Discriminant
      Analysis (NDA) were applied. First Nearest-Neighbour (1-NN) classifier was
      performed for the features resulting from PCA and LDA. NDA features were
      classified by artificial neural network (A-NN). Receiver operating characteristic
      (ROC) curve analysis was used for examining the performance of TA methods.
      RESULTS: The best results were driven in 1-99% normalization with features
      extracted by POE+ACC algorithm and analyzed by NDA with the area under the ROC
      curve ( Az) of 0.9722 which correspond to sensitivity of 94.45%, specificity of
      100%, and accuracy of 97.14%. CONCLUSION: Our results indicate that TA is a
      reliable method, can provide useful information help radiologist in detection and
      classification of benign and malignant thyroid nodules.

PMID- 25960850
TI  - Detection of Anticancer and Apoptotic Effect of the Produced IgYs against the
      Three Extracellular Domain of Human DR5 Protein.
AB  - BACKGROUND: TNFalpha cytokine family in the body plays divers' roles in the
      cellular events such as cell proliferation, differentiation, necrosis, septic
      shock and apoptosis. In response to TNF therapy, several cell signaling pathways
      activated in cells which in different manners can lead to apoptosis or necrosis.
      However induction of apoptosis is depended on one of its important members, TRAIL
      and its receptors that will be followed by apoptosis activity. Tumor necrosis
      factor-related apoptosis-inducing ligand (TRAIL) and especially the DR5, is
      generating considerable interests as a possible anticancer therapeutic agent
      because of its selective activation in apoptosis of this receptor as a superior
      affinity to ligands. METHODS: The study was performed in invitro assay and the
      anticancer effects of the produced antibodies were assumed by MTT and
      flowcytometric methods. In the first step for immunization of the hens, three
      selective small peptides from extracellular domain of DR5 which were chemically
      synthesized, injected to hens and after the proper immunization of them, IgYs
      were extracted from the egg yolk. After assumption of specificity of the purified
      IgYs against the whole DR5 protein, they were performed in MTT assay and
      flowcytometric colorimeter. RESULTS: After confirmation of synthesized peptides
      they were injected to hens with Fround's complete adjuvant. With completing the
      immunization procedure the specificity of purified IgYs were confirmed by ELISA.
      The antibodies were significantly killed the MCF7 breast cancer cells, but had
      divers affect (proliferative) on normal hepatocyte cells. Additionally,
      significantly they induced apoptosis on the cancerous cells in contrast to
      control cells. CONCLUSION: The results clearly demonstrated that the produced
      IgYs with reduced cost and time managing could remarkably use as an effective
      anticancer drug.

PMID- 25960852
TI  - Appearance of Acute Myelogenous Leukemia (AML) in a Patient with Breast Cancer
      after Adjuvant Chemotherapy: Case Report and Review of the Literature.
AB  - Acute Myelogenous Leukemia (AML) is an aggressive hematologic malignancy that
      cause by abnormal proliferation and accumulation of hematopoietic progenitor
      cells. A 37-year-old woman referred to oncologic clinic with a self-detected mass
      and pain in her left breast. The stage of tumor was IotaIotaIotaA. She was
      treated with the combination of anthracycline and cyclophosphamide for four
      courses, followed by four courses of paclitaxel with trastuzumab for one year.
      After 18 months of the first treatment for breast cancer, her bone marrow biopsy
      was compatible with AML-M2. Here, we are reporting a young woman case with breast
      cancer that developed AML malignancy during short interval of therapy. 

PMID- 25960853
TI  - Primary Ewing's Sarcoma/Primitive Neuroectodermal Tumor of of Kidney - a
      Diagnostic Dilemma.
AB  - Among the group of small round cell tumors of kidney Ewing's sarcoma/PNET is a
      very rare entity which has aggressive clinical course. We report a case of renal
      mass in 24 years old male which was histologically diagnosed as small round cell
      tumor of kidney. Arrangement of the malignant cell along with vascular network in
      a filigree pattern was suspicious for a diagnosis of Ewing's sarcoma/PNET which
      was confirmed by positivity of CD 99 immunohistochemically. Thus careful
      histological observation and immunohistochemical stains can give the proper
      diagnosis of primary Ewing's sarcoma/PNET thus removing the diagnostic dilemma in
      the group of small round cell tumors. 

PMID- 25960854
TI  - A case of rupioid syphilis masquerading as aggressive cutaneous lymphoma.
AB  - Secondary syphilis has been known since the late 19th century as the great
      imitator; however, some experts now regard cutaneous lymphoma as the great
      imitator of skin disease. Either disease, at times an equally fastidious
      diagnosis, has reported to mimic each other even. It is thus vital to consider
      these possibilities when presented with a patient demonstrating peculiar skin
      lesions. No other manifestation of secondary syphilis may pose such quandary as a
      rare case of rupioid syphilis impersonating cutaneous lymphoma. We present such a
      case, of a 36-year-old HIV positive male, misdiagnosed with aggressive cutaneous
      lymphoma, actually exhibiting rupioid syphilis thought secondary to immune
      reconstitution inflammatory syndrome (IRIS). 

PMID- 25960855
TI  - Age-standardized Incidence Rates for Leukemia Associated with Consanguineous
      Marriages in 68 Countries, an Ecological Study.
AB  - Consanguineous marriage that defines as a union between biologically related
      persons has a variety of known deleterious correlations with factors that affect
      public health within human populations. To investigate the association between
      the mean of inbreeding coefficient (alpha) and incidence of leukemia, the present
      ecological study on 68 countries was carried out. Statistical analysis showed
      that the age-standardized incidence rate of leukemia positively correlated with
      log10GNI per capita (r=0.699, df=66, P<0.001) and negatively correlated with
      log10alpha (r=-0.609, df=66, P<0.001). Controlling log10GNI per capita, a
      significant negative correlation between log10alpha and the age-standardized
      incidence rate of leukemia was observed (r=-0.392, df=65, P=0.001). The countries
      were stratified according to their annual GNI per capita, low and high-income
      countries with GNI per capita less than and more than 10,000$, respectively.
      Statistical analysis showed that in high-income countries, after controlling for
      log10GNI per capita, the correlation between the age-standardized incidence rate
      of leukemia and log10alpha was still significant (r=-0.600, df=36, P<0.001). It
      should be noted that there was no significant association between the age
      standardized mortality rate due to leukemia and log10alpha (P>0.05). The present
      finding indicates that the rate of leukemia, age-standardized for incidence, is
      lower in countries with a high prevalence of consanguineous marriages. 

PMID- 25960856
TI  - Disseminated Histoplasmosis in Immunocompetent Individuals- not a so Rare Entity,
      in India.
AB  - INTRODUCTION: Histoplasmosis is a rare fungal disease caused by dimorphic fungi
      Histoplasma capsulatum. The causative fungus persists in soil, infects through
      inhalation and manifests in three main types-acute primary, chronic cavitary and
      progressive disseminated histoplasmosis. Disseminated Histoplasmosis (DH) is
      defined as a clinical condition where the fungus is present in more than one
      location. Among the forms of histoplasmosis, DH is the rarest and mostly found in
      an immuno-compromised individual. Here we are presenting our experiences of the
      series of cases of DH in immuno-competent individuals who have been diagnosed in
      our institute in last 5 years. MATERIALS AND METHODS: This is a single centre
      retrospective observational study, conducted in Institute of Haematology and
      Transfusion Medicine, which is a referral centre for Eastern India, from May 2009
      to April 2014. Only cases with DH in otherwise healthy immuno-competent
      individuals were included in the study. The histoplasmosis was confirmed either
      by presence of Histoplasma in biopsy specimen from an extrapulmonary organ or by
      positive growth in fungal culture. RESULT: Total seven patients met the inclusion
      criteria. Five out of 7 patients were male. The mean age was 35 years. Five of
      the 7 patients presented with fever for a long duration. Six patients complained
      of significant weight loss before diagnosis. On examination, one patient had skin
      nodules, five patients had hepato-splenomegaly, and two patients had
      lymphadenopathy. The laboratory investigations revealed anaemia in six out of 7
      patients, and pancytopenia in 3 patients. Two patients had features of the
      hemophagocytic syndrome in the bone marrow. All patients were treated with
      conventional amphotericin B deoxycholate and azole antifungal. One patient with
      adrenal involvement died in hospital. The patient with skin nodule had recurrent
      relapses. The other patients had resolution of symptoms and were clinically
      cured. CONCLUSION: DH is not an uncommon aetiology of fever of prolonged duration
      even in immuno-competent individual and should be kept as a differential
      diagnosis. Targeted investigation through early bone marrow biopsy and fungal
      culture may help in the diagnosis of DH. Imaging study to exclude adrenal
      involvement prevents case fatality. Cytopenia may be due to a secondary
      hemophagocytic syndrome, which improves with anti-fungal therapy. Treatment with
      either amphotericin B or itraconazole gives excellent outcome though therapy may
      have to be given for a prolonged period in case of relapses.

PMID- 25960857
TI  - Is the incidence trend of heparin-induced thrombocytopenia decreased by the
      increased use of low-molecular-weight-heparin?
AB  - BACKGROUND: The increasing trend of using low-molecular-weight-heparin (LMWH)
      versus unfractionated heparin (UFH) in hospitalized adult patients is raising
      concerns about the incidence of heparin-induced thrombocytopenia (HIT). METHOD: A
      retrospective study analyzed the requests for heparin-induced antibodies by
      enzyme-linked immunosorbent assay (ELISA) among adult hospitalized patients
      during the period from January 2011 to December 2013. These patients received
      either UFH or LMWH for prevention or therapeutic indications. Those with positive
      immune-mediated HIT were identified and considered as case patients. RESULT: The
      usage of LMWH and UFH and development of HIT was determined during the study
      period. The incidence of HIT in patients receiving UFH and those receiving LMWH
      was 4.09 per thousand patients and 0.48 per thousand patients, respectively,
      (p<0.0001) with an overall incidence of 2.49 per thousand patients. CONCLUSION:
      The increased trend of using LMWH over UFH among hospitalized adult patients was
      observed and can be said to contribute to the diminished overall incidence of
      HIT.

PMID- 25960858
TI  - Nutritionally variant streptococci bacteremia in cancer patients: a retrospective
      study, 1999-2014.
AB  - BACKGROUND: Nutritionally variant Streptococci (NVS), Abiotrophia and
      Granulicatella are implicated in causing endocarditis and blood stream infections
      more frequently than other sites of infection. Neutropenia and mucositis are the
      most common predisposing factors for infection with other pathogens in cancer
      patients. In this study, we investigated the clinical characteristics of NVS
      bacteremia in cancer patients and identified risk factors and outcomes associated
      with these infections. MATERIALS AND METHODS: We retrospectively reviewed all
      cases of NVS bacteremia occurring from June 1999 to April 2014 at H. Lee Moffitt
      Cancer Center and Research Institute. The computerized epidemiology report
      provided by the microbiology laboratory identified thirteen cancer patients with
      NVS bacteremia. We collected data regarding baseline demographics and clinical
      characteristics such as age, sex, underlying malignancy, neutropenic status,
      duration of neutropenia, treatment, and outcome. RESULTS: Thirteen patients were
      identified with positive NVS blood stream infection. Ten patients (77%) had
      hematologic malignancies, including chronic lymphocytic leukemia (CLL)(1),
      multiple myeloma (MM)(1), acute myelogenous leukemia (AML)(4), and non-Hodgkin's
      lymphoma (NHL)(4). The non-hematologic malignancies included esophageal cancer(2)
      and bladder cancer (1). CONCLUSION: NVS should be considered as a possible agent
      of bacteremia in cancer patients with neutropenia and a breach in oral,
      gastrointestinal and genitourinary mucosa (gingivitis/mucositis).

PMID- 25960859
TI  - Community healthcare workers' perception of an educational intervention in the
      care of patients with sickle cell disease in Brazil.
AB  - INTRODUCTION: Despite advances in the management of sickle cell disease, gaps
      still exist in the training of primary healthcare professionals for monitoring
      patients with the disease. OBJECTIVE: To assess the perception of community
      healthcare workers about the care and monitoring of patients with sickle cell
      disease after an educational intervention. METHOD: This exploratory, descriptive,
      and the qualitative study was conducted in Montes Claros, state of Minas Gerais,
      Brazil. The intervention involved the educational training of community
      healthcare workers from the Family Health Program of the Brazilian Unified Health
      System. The focus group technique was used to collect the data. The following
      topics were covered in the discussion: assessment of educational workshops,
      changes observed in the perception of professionals after training, profile of
      home visits, and access to and provision of basic healthcare services to
      individuals with sickle cell disease. The discussions were tape-recorded and
      transcribed verbatim. The data were subjected to content analysis and empirically
      organized into two categories. RESULTS: Changes in the healthcare practices of
      community health workers were observed after the educational intervention. The
      prioritization of healthcare services for patients with sickle cell disease and
      monitoring of clinical warning signs in healthcare units were observed.
      Furthermore, changes were observed in the profile of home visits to patients,
      which were performed using a script provided in the educational intervention.
      CONCLUSION: The educational intervention significantly changed the work process
      of community health workers concerning patient monitoring in primary healthcare.

PMID- 25960860
TI  - Effect of nebulized colistin on the ventilator circuit: a prospective pilot case-
      control study from a single cancer center.
AB  - Nebulized colistin (NC) is used for the treatment of pneumonia due to multidrug-
      resistant Gram-negative bacteria. In this one-year case-control study, our
      objective was to evaluate the effect of NC on the ventilator circuit (VC)
      components. The case group consisted of 25 mechanically-ventilated patients who
      received NC for the treatment of nosocomial pneumonia while the control group was
      25 mechanically-ventilated patients who did not receive NC. Respiratory
      therapists inspected the VC every 4 hrs and whenever a ventilator alarm was
      reported. The VC component was changed if the alarm did not subside after
      necessary measures were performed. Patients from both groups were treated at the
      adult medical/surgical intensive care unit at King Hussein Cancer Center. In the
      case group, 22 (88%) patients required changing at least one of the circuit
      components (flow sensor, exhalation membrane, or nebulizer kit). The median
      number of changes (range) per patient of the flow sensor, exhalation membrane,
      and nebulizer kit were: 2 (1-3), 2 (1-6), and 1 (1-2), respectively. Large
      amounts of white crystals, which resembled the colistin powder, were reported on
      the replaced VC components. The flow sensor was changed in 2 control patients,
      but white crystals were absent. Crystals obtained from one case subject were
      confirmed to be colistin by chromatographic mass spectroscopy. Further studies
      are needed to evaluate the effect of crystal formation on the efficacy of NC and
      clinical outcomes. 

PMID- 25960861
TI  - Prognostic value of brain and acute leukemia cytoplasmic gene expression in
      egyptian children with acute myeloid leukemia.
AB  - BACKGROUND: Acute myeloid leukemia (AML) accounts for 25%-35% of acute leukemia
      in children. BAALC gene (Brain and Acute Leukemia Cytoplasmic gene) is a recently
      identified gene on chromosome 8q22.3 that has prognostic significance in AML. The
      aim of this work was to study the impact of BAALC gene expression on prognosis of
      AML in Egyptian children. PATIENTS AND METHODS: This study was conducted on 40
      Egyptian children with newly diagnosed AML who were subjected to full history
      taking, clinical examination and laboratory investigations including: complete
      blood count, LDH, bone marrow aspiration, cytochemistry, immunophenotyping and
      assessment of BAALC Gene by real time PCR in bone marrow aspirate mononuclear
      cells before the start of chemotherapy. RESULTS: Positive BAALC gene expression
      was found in 24 cases (60%) and negative expression in 16 cases (40%). Positive
      BAALC gene expression group includes 14 males and 10 females with mean age at
      presentation of 8.35+/-2.63 while negative BAALC gene expression includes 10
      males and 6 females with mean age at presentation of 7.74+/-3.23 with no
      statistically significant differences between patients with positive and negative
      BAALC gene expression regarding age, sex and clinical presentations at time of
      diagnosis including pallor, purpura, splenomegaly, hepatomegaly and
      lymphadenopathy and laboratory investigations including WBCs and platelets
      counts, hemoglobin and LDH levels, and peripheral blood and bone marrow blast
      cell counts. There was significant association between positive BAALC gene
      expression and M1 and M2 compared with negative BAALC gene expression which is
      significantly associated with M4. There were statistically significant
      differences in disease outcome between positive and negative BAALC gene
      expression groups with higher rate of relapse and death and lower rate of
      complete remission and disease free survival in positive BAALC gene expression
      group compared with negative BAALC gene expression group. (p = 0.017). CONCLUSION
      AND RECOMMENDATION: BAALC expression is an important bad prognostic factor in AML
      patients with normal karyotype and therefore we recommend its incorporation into
      novel risk-adapted therapeutic strategies to improve the currently disappointing
      cure rate of patients with AML.

PMID- 25960862
TI  - Rare cytogenetic abnormalities in myelodysplastic syndromes.
AB  - The karyotype represents one of the main cornerstones for the International
      Prognostic Scoring System (IPSS) and the revised IPSS-R (IPSS-R) that are most
      widely used for prognostication in patients with myelodysplastic syndromes (MDS).
      The most frequent cytogenetic abnormalities in MDS, i.e. del(5q), -7/del(7q), +8,
      complex karyotypes, or -Y have been extensively explored for their prognostic
      impact. The IPSS-R also considers some less frequent abnormalities such as
      del(11q), isochromosome 17, +19, or 3q abnormalities. However, more than 600
      different cytogenetic categories had been identified in a previous MDS study.
      This review aims to focus interest on selected rare cytogenetic abnormalities in
      patients with MDS. Examples are numerical gains of the chromosomes 11 (indicating
      rapid progression), of chromosome 14 or 14q (prognostically intermediate to
      favorable), -X (in females, with an intermediate prognosis), or numerical
      abnormalities of chromosome 21. Structural abnormalities are also considered,
      e.g. del(13q) that is associated with bone marrow failure syndromes and favorable
      response to immunosuppressive therapy. These and other rare cytogenetic
      abnormalities should be integrated into existing prognostication systems such as
      the IPSS-R. However, due to the very low number of cases, this is clearly
      dependent on international collaboration. Hopefully, this article will help to
      inaugurate this process. 

PMID- 25960863
TI  - Importance of classical morphology in the diagnosis of myelodysplastic syndrome.
AB  - Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders
      characterized by dysplastic, ineffective, clonal and neoplastic hematopoiesis.
      MDS represent a complex hematological problem: differences in disease
      presentation, progression and outcome have necessitated the use of classification
      systems to improve diagnosis, prognostication, and treatment selection. However,
      since a single biological or genetic reliable diagnostic marker has not yet been
      discovered for MDS, quantitative and qualitative dysplastic morphological
      alterations of bone marrow precursors and peripheral blood cells are still
      fundamental for diagnostic classification. In this paper, World Health
      Organization (WHO) classification refinements and current minimal diagnostic
      criteria proposed by expert panels are highlighted, and related problematic
      issues are discussed. The recommendations should facilitate diagnostic and
      prognostic evaluations in MDS and selection of patients for new effective
      targeted therapies. Although, in the future, morphology should be supplemented
      with new molecular techniques, the morphological approach, at least for the
      moment, is still the cornerstone for the diagnosis and classification of these
      disorders. 

PMID- 25960864
TI  - An unusual cause of anemia and encephalopathy.

PMID- 25960865
TI  - Cyclosporine ophthalmic emulsions for the treatment of dry eye: a review of the
      clinical evidence.
AB  - Dry eye has gained recognition as a public health problem given its high
      prevalence, morbidity and cost implications. Although dry eye is common and
      affects patients' quality of life, only one medication, cyclosporine 0.05%
      emulsion, has been approved by the US FDA for its treatment. In this review, we
      summarize the basic science and clinical data regarding the use of cyclosporine
      in the treatment of dry eye. Randomized controlled trials showed that
      cyclosporine emulsion outperformed vehicles in the majority of trials,
      consistently decreasing corneal staining and increasing Schirmer scores. Symptom
      improvement was more variable, however, with ocular dryness shown to be the most
      consistently improved symptom over vehicle.

PMID- 25960866
TI  - Division of labor between IRF1 and IRF2 in regulating different stages of
      transcriptional activation in cellular antiviral activities.
AB  - BACKGROUND: Cellular antiviral activities are critically controlled by
      transcriptional activation of interferon-inducible genes, involving interferon
      regulatory factors (IRFs). Previous data suggested that IRF1 is an activator and
      IRF2 is a repressor, which functionally antagonize each other in transcriptional
      regulation. However, it is not clear how these two factors function to regulate
      cellular antiviral activities. RESULTS: We show that IRF2 is critically required
      for the induction of the TLR3 and other interferon-inducible genes in a chromatin
      environment. While both IRF1 and IRF2 directly interact with the BAF chromatin
      remodeling complex, IRF2 is associated with the TLR3 promoter in the unstimulated
      state and IRF1 binding to the promoter is strongly induced by stimulation with
      interferon, suggesting that these two factors may function at different stages of
      gene induction in the recruitment of the BAF complex. IRF2 acts to maintain the
      basal level expression, an open chromatin structure, and active histone
      modification marks (H3K9, K14 acetylation and H3K4 tri-methylation) of the TLR3
      promoter in the unstimulated state, while IRF1 serves to rapidly activate the
      promoter upon stimulation. CONCLUSIONS: IRF1 and IRF2 of the IRF family of
      transcription factors play distinct roles in cellular response to viral
      infection. IRF2 binds to TLR3 and other IFN-inducible gene promoters and
      maintains an active chromatin structure in the unstimulated state, which is
      required for their induction, while IRF1 binding to these promoters activates
      their transcription upon viral infection. Thus, the division of labor between the
      IRF transcription factor family members plays a pivotal role in coordinating the
      transcriptional activation in the cellular antiviral response.

PMID- 25960867
TI  - Medical loss ratio as a potential regulatory tool in the Israeli healthcare
      system.
AB  - BACKGROUND: The growth of the private health insurance sector in Western
      countries, which is characterized by information deficiencies and limited
      competition, necessitates the implementation of effective regulatory tools. One
      measure which is widely used is the medical loss ratio (MLR). Our objective was
      to analyze how MLR is applied as a regulatory measure in the Israeli voluntary
      health insurance (VHI) market in order to promote the protection of
      beneficiaries. The study will examine MLR values and the use of this tool by
      regulators of VHI in Israel. METHODS: Descriptive analysis using 2005-2012 data
      from public reports of the Ministry of Health and the Ministry of Finance on VHI
      plans in three market segments: nonprofit health plans, group (collective)
      policies offered by commercial insurance companies and individual policies
      offered by commercial insurance companies. RESULTS: In 2012, 74% of the Israeli
      population owned VHI provided by nonprofit health plans and 43% owned VHI offered
      by for-profit commercial companies. At that time the MLRs of three nonprofit
      health plans were significantly lower than 80%, mostly in the upper layers of
      coverage. The MLR in the individual commercial segment was consistently low (38%
      in 2012). The use of MLR as a regulation tool was, and continues to be,
      relatively limited in all segments. CONCLUSION: The VHI in Israel covers several
      essential services that are not covered by the statutory benefits package as a
      result of budget constraints. Thus, due to the high penetration rate of VHI in
      Israel compared to European countries and the lower levels of MLR, in order to
      assure the protection of beneficiaries it may be warranted to increase the extent
      of regulation and adjust it to the nature of the services covered. This may
      include distinguishing between essential and nonessential coverages and
      implementation of the most suitable regulatory measures (such as an MLR
      threshold, limitation of services covered and adjusting the actuarial models to
      the beneficiaries' behavior), rather than focusing only on assuring solvency.

PMID- 25960869
TI  - Neuroscience, epigenetics and the intergenerational transmission of social life:
      exploring expectations and engagements.
AB  - Research in neuroscience and epigenetics is prominent in biomedicine and beyond.
      Some policy makers, health professionals and other citizens have intuited
      particular implications from these 'social biologies', leveraging them to support
      policies that many find problematic (e.g., around the early years). This enjoins
      scholarly attention to the uses to which science is put, but also to how and why
      biomedical knowledge comes to be imbued with certain kinds of salience (both by
      'advocates' and by 'critics').

PMID- 25949803
TI  - Adherence to Artemisinin Combination Therapy for the treatment of uncomplicated
      malaria in the Democratic Republic of the Congo.
AB  - Between 2011 and 2013 the number of recorded malaria cases had more than doubled,
      and between 2009 and 2013 had increased almost 4-fold in MSF-OCA (Medecins sans
      Frontieres - Operational Centre Amsterdam) programmes in the Democratic Republic
      of the Congo (DRC). The reasons for this rise are unclear. Incorrect intake of
      Artemisinin Combination Therapy (ACT) could result in failure to treat the
      infection and potential recurrence. An adherence study was carried out to assess
      whether patients were completing the full course of ACT. One hundred and eight
      malaria patients in Shamwana, Katanga province, DRC were visited in their
      households the day after ACT was supposed to be completed. They were asked a
      series of questions about ACT administration and the blister pack was observed
      (if available). Sixty seven (62.0%) patients were considered probably adherent.
      This did not take into account the patients that vomited or spat their pills or
      took them at the incorrect time of day, in which case adherence dropped to 46
      (42.6%). The most common reason that patients gave for incomplete/incorrect
      intake was that they were vomiting or felt unwell (10 patients (24.4%), although
      the reasons were not recorded for 22 (53.7%) patients). This indicates that there
      may be poor understanding of the importance of completing the treatment or that
      the side effects of ACT were significant enough to over-ride the pharmacy
      instructions. Adherence to ACT was poor in this setting. Health education
      messages emphasising the need to complete ACT even if patients vomit doses, feel
      unwell or their health conditions improve should be promoted. 

PMID- 25960870
TI  - BioMAJ2Galaxy: automatic update of reference data in Galaxy using BioMAJ.
AB  - BACKGROUND: Many bioinformatics tools use reference data, such as genome
      assemblies or sequence databanks. Galaxy offers multiple ways to give access to
      this data through its web interface. However, the process of adding new reference
      data was customarily manual and time consuming, even more so when this data
      needed to be indexed in a variety of formats (e.g. Blast, Bowtie, BWA, or 2bit).
      BioMAJ is a widely used and stable software that is designed to automate the
      download and transformation of data from various sources. This data can be used
      directly from the command line, in more complex systems, such as Mobyle, or by
      using a REST API. FINDINGS: To ease the process of giving access to reference
      data in Galaxy, we have developed the BioMAJ2Galaxy module, which enables the gap
      between BioMAJ and Galaxy to be bridged. With this module, it is now possible to
      configure BioMAJ to automatically download some reference data, to then convert
      and/or index it in various formats, and then make this data available in a Galaxy
      server using data libraries or data managers. CONCLUSIONS: The developments
      presented in this paper allow us to integrate the reference data in Galaxy in an
      automatic, reliable, and diskspace-saving way. The code is freely available on
      the GenOuest GitHub account (https://github.com/genouest/biomaj2galaxy).

PMID- 25960871
TI  - Investigation into the annotation of protocol sequencing steps in the sequence
      read archive.
AB  - BACKGROUND: The workflow for the production of high-throughput sequencing data
      from nucleic acid samples is complex. There are a series of protocol steps to be
      followed in the preparation of samples for next-generation sequencing. The
      quantification of bias in a number of protocol steps, namely DNA fractionation,
      blunting, phosphorylation, adapter ligation and library enrichment, remains to be
      determined. RESULTS: We examined the experimental metadata of the public
      repository Sequence Read Archive (SRA) in order to ascertain the level of
      annotation of important sequencing steps in submissions to the database. Using
      SQL relational database queries (using the SRAdb SQLite database generated by the
      Bioconductor consortium) to search for keywords commonly occurring in key
      preparatory protocol steps partitioned over studies, we found that 7.10%, 5.84%
      and 7.57% of all records (fragmentation, ligation and enrichment, respectively),
      had at least one keyword corresponding to one of the three protocol steps. Only
      4.06% of all records, partitioned over studies, had keywords for all three steps
      in the protocol (5.58% of all SRA records). CONCLUSIONS: The current level of
      annotation in the SRA inhibits systematic studies of bias due to these protocol
      steps. Downstream from this, meta-analyses and comparative studies based on these
      data will have a source of bias that cannot be quantified at present.

PMID- 25960873
TI  - Sustaining the gains made in malaria control and elimination.
AB  - Significant progress has been made in the last 25 years to reduce the malaria
      burden, but considerable challenges remain. These gains have resulted from large
      investments in a range of control measures targeting malaria. Fana and co-authors
      find a strong relationship between education level and net usage with malaria
      parasitemia in pregnant women, suggesting the need for targeted control
      strategies. Mayala and co-workers find important links between agriculture and
      malaria with implications for inter-sectoral collaboration for malaria control. 

PMID- 25960872
TI  - Lactococcus garvieae: a small bacteria and a big data world.
AB  - OBJECTIVE: To describe the importance of bioinformatics tools to analyze the big
      data yielded from new "omics" generation-methods, with the aim of unraveling the
      biology of the pathogen bacteria Lactococcus garvieae. METHODS: The paper
      provides the vision of the large volume of data generated from genome sequences,
      gene expression profiles by microarrays and other experimental methods that
      require biomedical informatics methods for management and analysis. RESULTS: The
      use of biomedical informatics methods improves the analysis of big data in order
      to obtain a comprehensive characterization and understanding of the biology of
      pathogenic organisms, such as L. garvieae. CONCLUSIONS: The "Big Data" concepts
      of high volume, veracity and variety are nowadays part of the research in
      microbiology associated with the use of multiple methods in the "omic" era. The
      use of biomedical informatics methods is a requisite necessary to improve the
      analysis of these data.

PMID- 25960874
TI  - Development of phenylboronic acid-functionalized nanoparticles for emodin
      delivery.
AB  - Stable and monodisperse phenylboronic acid-functionalized nanoparticles (PBA-NPs)
      were fabricated using 3-((acrylamido)methyl)phenylboronic acid homopolymer (PBAH)
      via solvent displacement technique. The effect of operating parameters, including
      stirring time, initial polymer concentration and the proportion of methanol on
      the self-assembly process were systematically investigated. The diameters of the
      PBA-NPs were increased as increasing the initial PBAH concentration and the
      proportion of methanol. Likewise, there was a linear dependence between the size
      of self-assembled nanoparticles and the polymer concentration. Moreover, the
      dissipative particle dynamics (DPD) simulation technique was used to investigate
      the mechanism of self-assembly behavior of PBAH, which indicated that the
      interior of PBA-NPs was hydrophobic and compact, and the boronic acid groups were
      displayed on both the outermost and interior of PBA-NPs. The resulting PBA-NPs
      could successfully encapsulate emodin through PBA-diol interaction and the
      encapsulation efficiency (EE%) and drug loading content (DLC%) of drug-loaded PBA
      NPs were 78% and 2.1%, respectively. Owing to the acid-labile feature of the
      boronate linkage, a reduction in environmental pH from pH 7.4 to 5.0 could
      trigger the disassociation of the boronate ester bonds, which could accelerate
      the drug release from PBA-Emodin-NPs. Besides, PBA-Emodin-NPs showed a much
      higher cytotoxicity to HepG2 cells (cancer cells) than that to MC-3T3-E1 cells
      (normal cells). These results imply that PBA-NPs would be a promising scaffold
      for the delivery of polyphenolic drugs.

PMID- 25960875
TI  - Spatial memory-based behaviors for locating sources of odor plumes.
AB  - BACKGROUND: Many animals must locate odorant point sources during key behaviors
      such as reproduction, foraging and habitat selection. Cues from such sources are
      typically distributed as air- or water-borne chemical plumes, characterized by
      high intermittency due to environmental turbulence and episodically rapid changes
      in position and orientation during wind or current shifts. Well-known examples of
      such behaviors include male moths, which have physiological and behavioral
      specializations for locating the sources of pheromone plumes emitted by females.
      Male moths and many other plume-following organisms exhibit "counter-turning"
      behavior, in which they execute a pre-planned sequence of cross-stream movements
      spanning all or part of an odorant plume, combined with upstream movements
      towards the source. Despite its ubiquity and ecological importance, theoretical
      investigation of counter-turning has so far been limited to a small subset of
      plausible behavioral algorithms based largely on classical biased random walk
      gradient-climbing or oscillator models. RESULTS: We derive a model of plume
      tracking behavior that assumes a simple spatially-explicit memory of previous
      encounters with odorant, an explicit statistical model of uncertainty about the
      plume's position and extent, and the ability to improve estimates of plume
      characteristics over sequential encounters using Bayesian updating. The model
      implements spatial memory and effective cognitive strategies with minimal neural
      processing. We show that laboratory flight tracks of Manduca sexta moths are
      consistent with predictions of our spatial memory-based model. We assess plume
      following performance of the spatial memory-based algorithm in terms of success
      and efficiency metrics, and in the context of "contests" in which the winner is
      the first among multiple simulated moths to locate the source. CONCLUSIONS: Even
      rudimentary spatial memory can greatly enhance plume-following. In particular,
      spatial memory can maintain source-seeking success even when plumes are so
      intermittent that no pheromone is detected in most cross-wind transits.
      Performance metrics reflect trade-offs between "risk-averse" strategies (wide
      cross-wind movements, slow upwind advances) that reliably but slowly locate odor
      sources, and "risk-tolerant" strategies (narrow cross-wind movements, fast upwind
      advances) that often fail to locate a source but are fast when successful.
      Success in contests of risk-averse vs. risk-tolerant behaviors varies strongly
      with the number of competitors, suggesting empirically testable predictions for
      diverse plume-following taxa. More generally, spatial memory-based models provide
      tractable, explicit theoretical linkages between sensory biomechanics,
      neurophysiology and behavior, and ecological and evolutionary dynamics operating
      at much larger spatio-temporal scales.

PMID- 25960876
TI  - Correction: Temperature of gas delivered from ventilators.
AB  - [This corrects the article on p. 6 in vol. 1, PMID: 25705400.]. 

PMID- 25960877
TI  - Procalcitonin for the differential diagnosis of infectious and non-infectious
      systemic inflammatory response syndrome after cardiac surgery.
AB  - BACKGROUND: This study was performed to assess the value of procalcitonin (PCT)
      for the differential diagnosis between infectious and non-infectious systemic
      inflammatory response syndrome (SIRS) after cardiac surgery. METHODS: Patients
      diagnosed with SIRS after cardiac surgery between April 1, 2011 and March 31,
      2013 were retrospectively studied. A total of 142 patients with SIRS, infectious
      (n = 47) or non-infectious (n = 95), were included. The patients with infectious
      SIRS included 11 with sepsis, 12 with severe sepsis without shock, and 24 with
      septic shock. RESULTS: PCT, C-reactive protein (CRP), and the white blood cell
      (WBC) count were significantly higher in the infectious SIRS group than in the
      non-infectious SIRS group. PCT had the highest sensitivity and specificity for
      differential diagnosis, with a cut-off value for infectious SIRS of 0.47 ng/mL.
      PCT was more reliable than CRP in diagnosing severe sepsis without shock, but it
      was not useful for diagnosing septic shock. The PCT cut-off value for diagnosing
      severe sepsis without shock was 2.28 ng/mL. CONCLUSIONS: PCT was a useful marker
      for the diagnosis of infectious SIRS after cardiac surgery. The optimal PCT cut
      off value for diagnosing infectious SIRS was 0.47 ng/mL.

PMID- 25960878
TI  - A pilot study of Bifidobacterium breve in neonates undergoing surgery for
      congenital heart disease.
AB  - BACKGROUND: Probiotics have currently been widely used in patients undergoing
      various types of surgeries and improved their clinical outcomes, while data in
      pediatric cardiac surgery have been lacking. We investigated the safety and
      effects on the intestinal microbiota of the probiotic Bifidobacterium breve in
      neonates undergoing surgery for congenital heart disease. METHODS: This pilot,
      randomized study was performed in a single-center, university hospital-based
      pediatric intensive care unit (PICU). Twenty-one neonates undergoing surgery for
      congenital heart disease at >7 days after birth were randomly allocated to two
      groups: group A received 3 * 10(9) colony-forming units (CFU)/day of enteral B.
      breve strain Yakult (BBG-01), which was started 1 week before and terminated 1
      week after surgery (n = 10), and group B did not receive BBG-01 (n = 11).
      RESULTS: The characteristics of the patients were similar in both groups. The
      postoperative days until fulfillment of the criteria for discharge from the PICU
      tended to be fewer in group A (8 [7-8] days) than in group B (9 [8-14] days) (p =
      0.10). Likewise, the postoperative days to enteral nutrition or achievement of
      caloric goal tended to be fewer in group A than in group B. The Bifidobacterium
      in fecal samples after initiating BBG-01 in group A were significantly higher in
      number than that in group B. Enterobacteriaceae were significantly fewer in group
      A than in group B immediately (7.0 [3.9-7.7] vs. 8.5 [8.0-9.1] log10 cells/g) and
      1 week (7.7 [7.0-8.1] vs. 9.3 [8.6-9.5] log10 cells/g) after surgery (p < 0.05
      for both comparisons). The number of Pseudomonas after 1 week was significantly
      lower in group A than in group B (p = 0.04). The concentrations of total organic
      and acetic acids were also significantly higher in group A than in group B. The
      postoperative course was uncomplicated and all neonates were discharged alive
      from the PICU. CONCLUSIONS: The perioperative administration of a probiotic to
      neonates undergoing surgery for congenital heart disease was safe and
      significantly improved their intestinal environment. The positive effects of this
      treatment on clinically significant outcomes remain to be investigated.

PMID- 25960879
TI  - Colloids to improve diuresis in critically ill patients: a systematic review.
AB  - BACKGROUND: The background of this study is to determine whether the addition of
      intravenous colloid to diuretic therapy, in comparison to diuretic therapy alone,
      improves diuresis and oxygenation and prevents intravascular volume depletion in
      intensive care unit (ICU) patients without shock. METHODS: We searched MEDLINE,
      Embase, Cochrane Register of Controlled Trials, Google Scholar, conference
      abstracts of ACCP, SCCM, ATS, and references of relevant articles. Randomized
      controlled trials (RCTs) of adult ICU patients, not in shock (defined as patients
      on low dose or no vasopressors, without need for IV fluid bolus or blood
      transfusion within 24 h), comparing intravenous colloid therapy (human albumin,
      plasma, synthetic starches, or gels) plus diuretic to control (diuretic alone, or
      diuretic plus placebo). Two reviewers independently applied eligibility criteria,
      assessed quality, and extracted data. RESULTS: Seven hundred fifty five studies
      were found in the initial search; 14 were deemed relevant; 2 were found to be
      eligible. There was good agreement between reviewers for study relevance (k =
      0.869) and eligibility (k = 0.811). One study of heart failure patients showed no
      evidence of improved mean or hourly urine output in the group receiving albumin.
      The second studied patients hypoproteinemic with ARDS and demonstrated an
      improved fluid balance in 3 days, improved oxygenation status, and improved serum
      albumin level in patients treated with albumin. No significant differences were
      found for other outcomes. No studies evaluating colloids other than albumin were
      found. CONCLUSIONS: Our review is limited by the small number of high-quality
      RCTs available to study this clinical question, both of which only studied
      albumin. High-quality RCTs are required to evaluate the effect of albumin as well
      as other colloids as an adjunct to diuresis in a general ICU population.

PMID- 25960880
TI  - Intensive care unit scoring systems outperform emergency department scoring
      systems for mortality prediction in critically ill patients: a prospective cohort
      study.
AB  - BACKGROUND: Multiple scoring systems have been developed for both the intensive
      care unit (ICU) and the emergency department (ED) to risk stratify patients and
      predict mortality. However, it remains unclear whether the additional data needed
      to compute ICU scores improves mortality prediction for critically ill patients
      compared to the simpler ED scores. METHODS: We studied a prospective
      observational cohort of 227 critically ill patients admitted to the ICU directly
      from the ED at an academic, tertiary care medical center. We compared Acute
      Physiology and Chronic Health Evaluation (APACHE) II, APACHE III, Simplified
      Acute Physiology Score (SAPS) II, Modified Early Warning Score (MEWS), Rapid
      Emergency Medicine Score (REMS), Prince of Wales Emergency Department Score
      (PEDS), and a pre-hospital critical illness prediction score developed by Seymour
      et al. (JAMA 2010, 304(7):747-754). The primary endpoint was 60-day mortality. We
      compared the receiver operating characteristic (ROC) curves of the different
      scores and their calibration using the Hosmer-Lemeshow goodness-of-fit test and
      visual assessment. RESULTS: The ICU scores outperformed the ED scores with higher
      area under the curve (AUC) values (p = 0.01). There were no differences in
      discrimination among the ED-based scoring systems (AUC 0.698 to 0.742; p = 0.45)
      or among the ICU-based scoring systems (AUC 0.779 to 0.799; p = 0.60). With the
      exception of the Seymour score, the ED-based scoring systems did not discriminate
      as well as the best-performing ICU-based scoring system, APACHE III (p = 0.005 to
      0.01 for comparison of ED scores to APACHE III). The Seymour score had a superior
      AUC to other ED scores and, despite a lower AUC than all the ICU scores, was not
      significantly different than APACHE III (p = 0.09). When data from the first 24 h
      in the ICU was used to calculate the ED scores, the AUC for the ED scores
      improved numerically, but this improvement was not statistically significant. All
      scores had acceptable calibration. CONCLUSIONS: In contrast to prior studies of
      patients based in the emergency department, ICU scores outperformed ED scores in
      critically ill patients admitted from the emergency department. This difference
      in performance seemed to be primarily due to the complexity of the scores rather
      than the time window from which the data was derived.

PMID- 25960881
TI  - Early prediction of acute kidney injury biomarkers after endovascular stent graft
      repair of aortic aneurysm: a prospective observational study.
AB  - BACKGROUND: Acute kidney injury (AKI) is a common and serious condition usually
      detected some time after onset by changes in serum creatinine (sCr). Although
      stent grafting to repair aortic aneurysms is associated with AKI caused by
      surgical procedures or the use of contrast agents, early biomarkers for AKI have
      not been adequately examined in stent graft recipients. We studied biomarkers
      including urinary neutrophil gelatinase-associated lipocalin (NGAL), blood NGAL,
      N-acetyl-beta-d-glucosaminidase (NAG), microalbumin (Alb), and liver fatty acid
      binding protein (L-FABP) as prospective early biomarkers for AKI in patients who
      had received stent graft repairs of aortic aneurysms. METHODS: In addition to pre
      surgical sampling, at 2 to 6 h and at 1, 3 to 4, and 5 days or later (until
      stable) after surgery, urine and serum biomarkers were sampled from 47 patients
      who underwent stent graft repair of aortic aneurysms. RESULTS: Using Acute Kidney
      Injury Network criteria, 6 (14%) of 42 retained patients developed AKI. NGAL
      corrected with urine Cr (NGAL/Cr) values demonstrated the best predictive value
      for AKI (97% specificity, 83% sensitivity at a 65.1 MUg/gCr cutoff). The area
      under the receiver-operator characteristic curve of NGAL/Cr value 2 h after
      surgery was 0.9. Although NGAL/Cr, L-FABP corrected with urine Cr (L-FABP/Cr), L
      FABP, NAG, and Alb corrected by urine Cr (Alb/Cr) all reached peak values before
      AKI detection by sCr in AKI patients, all biomarkers reached the cutoff value
      before AKI detection after adaption of cutoff value. CONCLUSIONS: After stent
      graft repair of aortic aneurysm, NGAL/Cr is a potentially useful early biomarker
      for AKI.

PMID- 25960882
TI  - Increased prothrombotic property as a risk factor of acute kidney injury after
      surgical repair of abdominal aortic aneurysm: a prospective observational study.
AB  - BACKGROUND: Acute kidney injury (AKI) is one of the major morbidities after
      surgical repair of abdominal aortic aneurysm (AAA); however, precise pathogenesis
      of this morbidity has not been well determined. Since prothrombotic coagulation
      abnormality may precede organ dysfunction in systemic inflammatory state, we
      examined the kinetics of von Willebrand factor (VWF) and a disintegrin-like
      metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13), a cleaving enzyme
      of VWF, on the development of AKI after AAA surgery. METHODS: The kinetics of
      ADAMTS13 and VWF were examined in ten patients who underwent surgical repair of
      AAA. The changes in plasma neutrophil gelatinase-associated lipocalin (NGAL), a
      novel biomarker for AKI, and serum creatinine concentration were also examined at
      four points until seventh postoperative day (POD). Clinical diagnosis of AKI was
      based on the change in serum creatinine concentration and urine output according
      to Acute Kidney Injury Network (AKIN) criteria. RESULTS: ADAMTS13 activity was
      significantly lower than normal level before the surgery and showed a trend of
      decrease toward 3POD. The VWF/ADAMTS13 ratio showed a significant increase on
      1POD, which persisted until 7POD. None of patents was diagnosed as AKI based on
      AKIN criteria, although two patients received furosemide and/or carperitide
      therapy because of decreased urine output less than 0.5 ml/kg/h for several hours
      in ICU. Plasma NGAL showed a trend to increase after the surgery, which was
      significant on 3POD. The change in plasma NGAL was significantly correlated with
      VWF/ADAMTS13 ratio (P < 0.01). CONCLUSIONS: This study has shown that patients
      undergoing AAA surgery were prothrombotic after the surgery because of high
      VWF/ADAMTS13 ratio. Correlation between VWF/ADAMTS13 ratio and NGAL might
      indicate contribution of thrombotic event to subclinical AKI in the patients
      undergoing AAA surgery.

PMID- 25960884
TI  - The Canadian Childhood Nephrotic Syndrome (CHILDNEPH) Project: overview of design
      and methods.
AB  - BACKGROUND: Nephrotic syndrome is a commonly acquired kidney disease in children
      that causes significant morbidity due to recurrent episodes of heavy proteinuria.
      The management of childhood nephrotic syndrome is known to be highly variable
      among physicians and care centres. OBJECTIVES: The primary objective of the study
      is to determine centre-, physician-, and patient-level characteristics associated
      with steroid exposure and length of steroid treatment. We will also determine the
      association of dose and duration of steroid treatment and time to first relapse
      as a secondary aim. An embedded qualitative study utilizing focus groups with
      health care providers will enrich the quantitative results by providing an
      understanding of the attitudes, beliefs and local contextual factors driving
      variation in care. DESIGN: Mixed-methods study; prospective observational cohort
      (quantitative component), with additional semi-structured focus groups of
      healthcare professionals (qualitative component). SETTING: National study,
      comprised of all 13 Canadian pediatric nephrology clinics. PATIENTS: 400 patients
      under 18 years of age to be recruited over 2.5 years. MEASUREMENTS: Steroid doses
      for all episodes (first presentation, first and subsequent relapses) tracked over
      course of the study. Physician and centre-level characteristics catalogued, with
      reasons for treatment preferences documented during focus groups. METHODS: All
      patients tracked prospectively over the course of the study, with data comprising
      a prospective registry. One focus group at each site to enrich understanding of
      variation in care. LIMITATIONS: Contamination of treatment protocols between
      physicians may occur as a result of concurrent focus groups. CONCLUSIONS:
      Quantitative and qualitative results will be integrated at end of study and will
      collectively inform strategies for the development and implementation of
      standardized evidence-based protocols across centres.

PMID- 25960883
TI  - Risk factors associated with hemodialysis central venous catheter malfunction; a
      retrospective analysis of a randomized controlled trial.
AB  - BACKGROUND: We previously reported a reduction in central venous catheter (CVC)
      malfunction when using once-weekly recombinant tissue-plasminogen activator (rt
      PA) as a locking solution, compared with thrice-weekly heparin. OBJECTIVES: To
      identify risk factors for CVC malfunction to inform a targeted strategy for rt-PA
      use. DESIGN: Retrospective analysis. SETTING: Canadian hemodialysis (HD) units.
      PATIENTS: Adults with newly placed tunnelled upper venous system CVCs randomized
      to a locking solution of rt-PA(1 mg/mL) mid-week and heparin (5000 u/ml) on the
      other HD sessions, or thrice-weekly heparin (5000 u/ml). MEASUREMENTS: CVC
      malfunction (the primary outcome) was defined as: peak blood flow less than 200
      mL/min for thirty minutes during a HD session; mean blood flow less than 250
      mL/min for two consecutive HD sessions; inability to initiate HD. METHODS: Cox
      regression was used to determine the association between patient demographics, HD
      session CVC-related variables and the outcome of CVC malfunction. RESULTS:
      Patient age (62.4 vs 65.4 yr), proportion female sex (35.6 vs 48.4%), and
      proportion with first catheter ever (60.7 vs 61.3%) were similar between patients
      with and without CVC malfunction. After multivariate analysis, risk factors for
      CVC malfunction were mean blood processed < 65 L when compared with >= 85 L in
      the prior 6 HD sessions (HR 4.36; 95% CI, 1.59 to 11.95), and mean blood flow <
      300 mL/min, or 300 - 324 mL/min in the prior 6 HD sessions (HR 7.65; 95% CI, 2.78
      to 21.01, and HR 5.52; 95% CI, 2.00 to 15.23, respectively) when compared to >=
      350 mL/min. LIMITATIONS: This pre-specified post-hoc analysis used a definition
      of CVC malfunction that included blood flow, which may result in an overestimate
      of the effect size. Generalizability of results to HD units where trisodium
      citrate locking solution is used may also be limited. CONCLUSIONS: HD session
      characteristics including mean blood processed and mean blood flow were
      associated with CVC malfunction, while patient characteristics were not. Whether
      targeting these patients at greater risk of CVC malfunction with rt-PA as a
      locking solution improves CVC longevity remains to be determined.

PMID- 25960885
TI  - Fluid balance, change in serum creatinine and urine output as markers of acute
      kidney injury post cardiac surgery: an observational study.
AB  - BACKGROUND: Acute kidney injury (AKI) is defined as oliguria or rise in serum
      creatinine but oliguria alone as a diagnostic criterion may over-diagnose AKI.
      OBJECTIVES: Given the association between fluid overload and AKI, we aimed to
      determine if positive fluid balance can complement the known parameters in
      assessing outcomes of AKI. DESIGN: Prospective observational study. SETTING:
      Teaching hospital in Vancouver, Canada. PATIENTS: 111 consecutive patients
      undergoing elective cardiac surgery from January to April 2012. MEASUREMENTS:
      Outcomes of cardiac surgery intensive care unit (CSICU) and hospital length of
      stay (LOS) in relation to fluid balance, urine output and serum creatinine.
      METHODS: All fluid input and output was recorded for 72 hours post-operatively.
      Positive fluid balance was defined as >6.5 cc/kg. Daily serum creatinine and
      hourly urine output were recorded and patients were defined as having AKI
      according to the AKIN criteria. RESULTS: Of the patients who were oliguric, those
      with fluid overload trended towards longer LOS than those without fluid overload
      [CSICU LOS: 62 and 39 hours (unadjusted p-value 0.02, adjusted p-value 0.58);
      hospital LOS: 13 and 9 days (unadjusted p-value: 0.05, adjusted p-value: 0.16)].
      Patients with oliguria who were fluid overloaded had similar LOS to patients with
      overt AKI (change in serum creatinine >= 26.5 umol/L), [CSICU LOS: 62 and 69
      hours (adjusted p value: 0.32) and hospital LOS: 13 and 14 days (adjusted p
      value: 0.19)]. Patients with oliguria regardless of fluid balance had longer
      CSICU LOS (adjusted p value: 0.001) and patients who were fluid overloaded in the
      absence of AKI had longer hospital LOS (adjusted p value: 0.02). LIMITATIONS:
      Single centre, small sample, LOS as outcome. CONCLUSIONS: Oliguria and positive
      fluid balance is associated with a trend towards longer LOS as compared to
      oliguria alone. Fluid balance may therefore be a useful marker of AKI, in
      addition to urine output and serum creatinine.

PMID- 25960886
TI  - Improving prevention, early recognition and management of acute kidney injury
      after major surgery: results of a planning meeting with multidisciplinary
      stakeholders.
AB  - PURPOSE OF REVIEW: Acute kidney injury (AKI) is common after major surgery, and
      is associated with morbidity, mortality, increased length of hospital stay, and
      high health care costs. Although recent guidelines for AKI provide
      recommendations for identification of patients at risk, monitoring, diagnosis,
      and management of AKI, there is lack of understanding to guide successful
      implementation of these recommendations into clinical practice. SOURCES OF
      INFORMATION: We held a planning meeting with multidisciplinary stakeholders to
      identify barriers, facilitators, and strategies to implement recommendations for
      prevention, early identification, and management of AKI after major surgery.
      Barriers and facilitators to knowledge use for peri-operative AKI prevention and
      care were discussed. FINDINGS: Stakeholders identified barriers in knowledge (how
      to identify high-risk patients, what criteria to use for diagnosis of AKI),
      attitudes (self-efficacy in preventive care and management of AKI), and behaviors
      (common use of diuretics, non-steroidal anti-inflammatory drugs, withholding of
      intravenous fluids, and competing time demands in peri-operative care).
      Educational, informatics, and organizational interventions were identified by
      stakeholders as potentially useful elements for future interventions for peri
      operative AKI. LIMITATION: Meeting participants were from a single centre.
      IMPLICATIONS: The information and recommendations obtained from this
      stakeholder's meeting will be useful to design interventions to improve
      prevention and early care for AKI after major surgery.

PMID- 25960887
TI  - Brief communication: patient satisfaction with the use of tablet computers: a
      pilot study in two outpatient home dialysis clinics.
AB  - BACKGROUND: Electronic capture of patients' reports of their health is
      significant in clinical nephrology research because health-related quality of
      life (HRQOL) for patients with end-stage renal disease is compromised and
      assessment by patients of their HRQOL in practice is relatively uncommon.
      OBJECTIVE: The purpose of this study was to evaluate patient satisfaction with
      and time involved in administering HRQOL and symptom assessment measures using
      tablet computers in two outpatient home dialysis clinics. DESIGN: A cross
      sectional observational study design was employed. SETTING: The study was
      conducted in two home dialysis clinics. PATIENTS: Fifty-six patients participated
      in the study; 35 males (63%) and 21 females (37%) with a mean age of 66 +/- 12
      (36-90 years old) were included. Forty-nine participants were on peritoneal
      dialysis (87%), 6 on home hemodialysis (11%), and 1 on nocturnal home
      hemodialysis (2%). MEASUREMENTS: Measures included the Kidney Disease Quality of
      Life-36 (KDQOL-36), the Edmonton Symptom Assessment Scale (ESAS) and
      Participant's Level of Satisfaction in Using a Tablet Computer. METHODS: Using a
      tablet computer, participants completed the three measures. Descriptive
      statistics and bivariate correlations were calculated. RESULTS: Participants'
      satisfaction with use of the tablet computer was high; 66% were "very satisfied",
      7% "satisfied", 2% "slightly satisfied", and 18% "neutral". On the 7-point Likert
      type scale, the mean satisfaction score was 5.11 (SD = 1.6). Mean time to
      complete the measures was: Level of Satisfaction 1.15 minutes (SD = 0.41), ESAS
      2.55 minutes (SD = 1.04), and KDQOL 9.56 minutes (SD = 2.03); the mean time to
      complete all three instruments was 13.19 minutes (SD = 2.42). There were no
      significant correlations between level of satisfaction and age, gender, HRQOL,
      time taken to complete surveys, computer experience, or comfort with technology.
      Comfort with technology and computer experience were highly correlated, r = .7, p
      (one-tailed) < 0.01. LIMITATIONS: Limitations include lack of generalizability
      because of a small self-selected sample of relatively healthy patients and a lack
      of psychometric testing on the measure of satisfaction. CONCLUSIONS: Participants
      were satisfied with the platform and the time involved for completion of
      instruments was modest. Routine use of HRQOL measures for clinical purposes may
      be facilitated through use of tablet computers.

PMID- 25960888
TI  - Thickness mapping of eleven retinal layers segmented using the diffusion maps
      method in normal eyes.
AB  - This study was conducted to determine the thickness map of eleven retinal layers
      in normal subjects by spectral domain optical coherence tomography (SD-OCT) and
      evaluate their association with sex and age. Mean regional retinal thickness of
      11 retinal layers was obtained by automatic three-dimensional diffusion map based
      method in 112 normal eyes of 76 Iranian subjects. We applied our previously
      reported 3D intraretinal fast layer segmentation which does not require edge
      based image information but rather relies on regional image texture. The
      thickness maps are compared among 9 macular sectors within 3 concentric circles
      as defined by ETDRS. The thickness map of central foveal area in layers 1, 3, and
      4 displayed the minimum thickness. Maximum thickness was observed in nasal to the
      fovea of layer 1 and in a circular pattern in the parafoveal retinal area of
      layers 2, 3, and 4 and in central foveal area of layer 6. Temporal and inferior
      quadrants of the total retinal thickness and most of other quadrants of layer 1
      were significantly greater in the men than in the women. Surrounding eight
      sectors of total retinal thickness and a limited number of sectors in layers 1
      and 4 significantly correlated with age. 

PMID- 25960889
TI  - Maternal Obesity Management Using Mobile Technology: A Feasibility Study to
      Evaluate a Text Messaging Based Complex Intervention during Pregnancy.
AB  - BACKGROUND: Maternal obesity and excessive gestational weight gain (GWG) are on
      the rise with negative impact on pregnancy and birth outcomes. Research into
      managing GWG using accessible technology is limited. The maternal obesity
      management using mobile technology (MOMTech) study aimed at evaluating the
      feasibility of text messaging based complex intervention designed to support
      obese women (BMI >= 30) with healthier lifestyles and limit GWG. METHODS:
      Participants received two daily text messages, supported by four appointments
      with healthy lifestyle midwife, diet and activity goal setting, and self
      monitoring diaries. The comparison group were obese mothers who declined to
      participate but consented for their routinely collected data to be used for
      comparison. Postnatal interviews and focus groups with participants and the
      comparison group explored the intervention's acceptability and suggested
      improvements. RESULTS: Fourteen women completed the study which did not allow
      statistical analyses. However, participants had lower mean GWG than the
      comparison group (6.65 kg versus 9.74 kg) and few (28% versus 50%) exceeded the
      Institute of Medicine's upper limit of 9 kg GWG for obese women. CONCLUSIONS:
      MOMTech was feasible within clinical setting and acceptable intervention to
      support women to limit GWG. Before further trials, slight modifications are
      planned to recruitment, text messages, and the logistics of consultation visits.

PMID- 25960890
TI  - Using computed tomography scans and patient demographic data to estimate thoracic
      epidural space depth.
AB  - Background and Objectives. Previous studies have used varying methods to estimate
      the depth of the epidural space prior to placement of an epidural catheter. We
      aim to use computed tomography scans, patient demographics, and vertebral level
      to estimate the depth of the loss of resistance for placement of thoracic
      epidural catheters. Methods. The records of consecutive patients who received a
      thoracic epidural catheter were reviewed. Patient demographics, epidural
      placement site, and technique were collected. Preoperative computed tomography
      scans were reviewed to measure the skin to epidural space distance. Linear
      regression was used for a multivariate analysis. Results. The records of 218
      patients were reviewed. The mean loss of resistance measurement was significantly
      larger than the mean computed tomography epidural space depth measurement by 0.79
      cm (p < 0.001). Our final multivariate model, adjusted for demographic and
      epidural technique, showed a positive correlation between the loss of resistance
      and the computed tomography epidural space depth measurement (R (2) = 0.5692, p <
      0.0001). Conclusions. The measured loss of resistance is positively correlated
      with the computed tomography epidural space depth measurement and patient
      demographics. For patients undergoing thoracic or abdominal surgery, estimating
      the loss of resistance can be a valuable tool. 

PMID- 25960891
TI  - A giant left atrial myxoma neovascularized from the right coronary artery.
AB  - Myxomas are benign and the most common tumors of the cardiac muscle (Reynen,
      1995). They are predominantly located in the left atrium. Clinical manifestations
      may vary according to the localization and the size of the myxoma. On the other
      hand, imaging of a myxoma by contrast dye during coronary angiography is a rare
      sign, which displays the vascular supply of the tumor. Here, we report the case
      of a 51-year-old man presenting with presyncope and palpitations due to a giant
      left atrial myxoma having its vascular supply from the right coronary artery
      (RCA). 

PMID- 25960892
TI  - The Significance of ST Depression in a Postmenopausal Woman on Estrogen Therapy
      during Regadenoson Myocardial SPECT Imaging.
AB  - The incidence of false-positive stress tests has been noted in women, especially
      on hormone replacement therapy. Current literature describes this phenomenon in
      treadmill and adenosine stress tests. The introduction of regadenoson as a
      vasodilator agent has been widely adopted owing to its potency and specificity.
      To our knowledge, false-positive stress test with regadenoson in a postmenopausal
      woman on estrogen has never been described. Given the higher chronotropic
      response with regadenoson, we believe that normal perfusion images with a higher
      heart rate response indicate a good prognosis in such patients. 

PMID- 25960893
TI  - The unexpected pitter patter: new-onset atrial fibrillation in pregnancy.
AB  - Background. Atrial fibrillation is a relatively uncommon but dangerous
      complication of pregnancy. Emergency physicians must know how to treat both
      stable and unstable tachycardias in late pregnancy. In this case, a 40-year-old
      female with a cerclage due to incompetent cervix and previous preterm deliveries
      presents in new-onset atrial fibrillation. Case Report. A previously healthy 40
      year-old African American G2 P1 female with a 23-week twin gestation complicated
      by an incompetent cervix requiring a cervical cerclage presented to the emergency
      department with intermittent palpitations and shortness of breath for the past
      two months. EMS noted the patient to have a tachydysrhythmia, atrial fibrillation
      with rapid ventricular response. She was placed on a diltiazem drip, which was
      titrated to 15 mg/hr without successful rate control. Her heart rate remained in
      the 130s and the rhythm continued to be atrial fibrillation with RVR. Digoxin was
      then added as a second agent, and discussions about the potential risks of
      cardioversion in pregnancy ensued. Fortunately, the patient converted to sinus
      rhythm before cardioversion became necessary. The digoxin was discontinued; the
      diltiazem was also discontinued after the patient subsequently developed
      hypotension. "Why Should Emergency Physicians Be Aware of This?" New-onset atrial
      fibrillation is rare in pregnancy but can increase the mortality and morbidity of
      the mother and fetus if not treated promptly. 

PMID- 25960894
TI  - Amphetamine-Like Analogues in Diabetes: Speeding towards Ketogenesis.
AB  - Obesity is common in patients with type 1 and type 2 diabetes. Amphetamine-like
      analogues comprise the most popular class of weight loss medications. We present
      a case of a 34-year-old African American female with a history of type 1
      diabetes, dyslipidemia, and obesity who developed diabetic ketoacidosis (DKA)
      after starting Diethylpropion for the purpose of weight loss. Shortly after
      starting Diethylpropion, she developed nausea, vomiting, and periumbilical pain.
      Blood work revealed glucose of 718 mg/dL, pH 7.32 (7.35-7.45), bicarbonate 16
      mmol/L (22-29 mmol/L), and anion gap 19 mmol/L (8-16 mmol/L). Urine analysis
      demonstrated large amount of ketones. She was hospitalized and successfully
      treated for DKA. Diethylpropion was discontinued. Amphetamine-like analogues
      administration leads to norepinephrine release from the lateral hypothalamus
      which results in the appetite suppression. Peripheral norepinephrine
      concentration rises as well. Norepinephrine stimulates adipocyte lipolysis and
      thereby increases nonesterified fatty acids (NEFA) availability. It promotes beta
      oxidation of NEFA to ketone bodies while decreasing metabolic clearance rate of
      ketones. In the setting of acute insulin deficiency these effects are augmented.
      Females are more sensitive to norepinephrine effects compared to males. In
      conclusion, amphetamine-like analogues lead to a release of norepinephrine which
      can result in a clinically significant ketosis, especially in the setting of
      insulin deficiency. 

PMID- 25960895
TI  - Successful aortic aneurysm repair in a woman with severe von Willebrand (type 3)
      disease.
AB  - von Willebrand disease type 3 (VWD3) is a rare but the most severe form of von
      Willebrand disease; it is due to almost complete lack of von Willebrand factor
      activity (VWF:RCo). It is inherited as autosomal recessive trait; whilst
      heterozygote carriers have mild, or no symptoms, patients with VWD3 show severe
      bleeding symptoms. In the laboratory, this is characterised by undetectable
      VWF:Ag, VWF:RCo, and reduced levels of factor VIII < 0.02 IU/dL. The bleeding is
      managed with von Willebrand/FVIII factor concentrate replacement therapy. In this
      rare but challenging case we report on the successful excision and repair of an
      ascending aortic aneurysm following adequate VWF/FVIII factor concentrate
      replacement using Haemate-P. 

PMID- 25960896
TI  - Nonsecretory multiple myeloma presenting as an intestinal tumor.
AB  - We report a case of a 43-year-old Caucasian man who presented with colicky
      abdominal pain and microcytic hypochromic anemia. The patient underwent a
      colonoscopy where a tumor was seen in the ascending colon; histology showed
      plasmacytoma of the colon. From the protein electrophoresis, no monoclonal band
      or free light chains were detected nor was urinary Bence Jones protein present. A
      bone marrow biopsy showed plasma cell myeloma. To the best of our knowledge, this
      is the first case of nonsecretory multiple myeloma presenting as plasmacytoma of
      the colon. 

PMID- 25960897
TI  - Two brothers with bardet-biedl syndrome presenting with chronic renal failure.
AB  - Bardet-Biedl Syndrome (BBS) is a rarely seen autosomal recessive transfer disease
      characterised by retinal dystrophy, obesity, extremity deformities, mental
      retardation, and renal and genital system anomalies. BBS shows heterogenic
      transfer. To date, 18 genes (BBS1-18) and 7 BBS proteins have been defined as
      related to BBS. All of the defined BBS genes have been shown to be related to the
      biogenesis or function of cilia. Renal failure accompanying the syndrome,
      especially in the advanced stages, is the most common cause of mortality.
      Therefore, as one of the major diagnostic criteria, renal damage is of great
      importance in early diagnosis. This paper presents the cases of two brothers with
      BBS who presented with chronic renal failure. 

PMID- 25960898
TI  - Neuralgia of the glossopharyngeal nerve in a patient with posttonsillectomy
      scarring: recovery after local infiltration of procaine-case report and
      pathophysiologic discussion.
AB  - We describe a patient with a three-year history of severe progressive left-sided
      glossopharyngeal neuralgia (GPN) that failed to adequately respond to various
      drug therapies. The application of lidocaine spray to the posterior pharyngeal
      wall provided no more than short-term relief. Apart from a large hypertrophic
      tonsillectomy scar on the left side all clinical and radiologic findings were
      normal. In terms of therapeutic local anaesthesia, the hypertrophic tonsillectomy
      scar tissue was completely infiltrated with the local anaesthetic (LA) procaine
      1%. The patient has been almost completely pain-free ever since, and the
      lidocaine spray is no longer needed. Six weeks after the first treatment a repeat
      infiltration of the tonsillectomy scar led to the complete resolution of all
      symptoms. The patient has become totally symptom-free without the need to take
      any medication now for two and a half years. This is the first report of a
      successful therapeutic infiltration of a tonsillectomy scar using an LA in a
      patient with GPN that has been refractory to medical treatment for several years.
      A possible explanation may be that the positive feedback loop maintaining
      neurogenic inflammation is disrupted and "sympathetically maintained pain"
      resolved by LA infiltration. 

PMID- 25960899
TI  - Cavernous hemangioma of the skull and meningioma: association or coincidence?
AB  - Intraosseous cavernous hemangiomas of the skull are rare. Meningiomas are quite
      frequently encountered in a neurosurgical practice. The association between these
      two entities is nevertheless very uncommon. The authors present a case of a 72
      year-old woman suffering from headache. The MRI showed a parietal meningioma with
      adjacent thick bone. The meningioma and the bone were removed. The histological
      examination confirmed the diagnosis of meningioma and revealed a cavernoma of the
      skull. The relationship between the lesions suggests more than a coincidental
      association. Several hypotheses are proposed to explain common causal
      connections. 

PMID- 25960900
TI  - Decidualized ovarian mass mimicking malignancy.
AB  - Deciduosis classically occurs in the context of known endometriosis in the
      pelvis, most commonly in the ovaries, but also in the peritoneum. However,
      ovarian deciduosis outside the context of endometriosis is rare and makes
      diagnosis difficult, especially as the sonographic appearance suggests a
      malignant process. We report a case of decidualized ovarian mass in a patient
      without prior history of endometriosis that mimicked an ovarian malignancy. MRI
      may be a useful imaging modality to monitor these lesions and guide management.
      Consultation with a multidisciplinary team accustomed to such conditions will
      help to tailor the management to each individual. 

PMID- 25960901
TI  - Conservative Treatment of Ewing's Sarcoma of the Uterus in Young Women.
AB  - Ewing sarcoma-primitive neuroectodermal tumors (ES/PNETs) constitute a family of
      neoplasms characterized by a continuum of neuroectodermal differentiations.
      ES/PNET of the uterus is rare. There are 48 cases of ES/PNET of the uterus
      published in the literature as far as we know. We describe a case of Ewing
      sarcoma of the uterus occurring in a 17-year-old woman presenting with a two
      month history of pelvic pain. After surgical excision and microscopic,
      immunohistochemical, and electron microscopy examination, the diagnosis of Ewing
      sarcoma of the uterus was suggested. This report will discuss the diagnosis and
      surgical and clinical management of Ewing uterine sarcoma in young women,
      according to the available literature. In spite of the rarity of ES/PNETs, they
      should be taken into account in the differential diagnosis of uterine neoplasms
      in young women. 

PMID- 25960902
TI  - Phyllodes tumor of the breast metastasizing to the vulva.
AB  - Phyllodes tumors of the breast are rare breast tumors that resemble fibroadenoma.
      They are composed of two types of tissues: stromal and glandular tissues. Unlike
      fibroadenoma, they are commonly found in the third decade of life and they tend
      to grow more rapidly. Depending on the relative components of the cells and
      mitotic activity, they are classified into benign, borderline, and malignant.
      They are usually present as a lump in the breast. Phyllodes tumors are usually
      managed by wide excision. The excision should be wide enough to ensure a tumor
      free margin. Recurrence rate is very high and most recurrences are usually local.
      Metastasis to the vulva has not been reported. 

PMID- 25960903
TI  - Conservative management in congenital bilateral upper eyelid eversion.
AB  - Aim. To report the case of congenital bilateral upper eyelid eversion with severe
      chemosis that was successfully managed conservatively. Report. The patient was a
      six-hour-old male neonate with bilateral congenital upper eyelid eversion and
      severe chemosis, following uneventful delivery. Conservative management consisted
      of the application of antibiotic ointment and padding the exposed conjunctiva
      with 5% hypertonic saline-soaked gauze. The eyelids reverted spontaneously on day
      3 and the condition was completely resolved by the third week. Conclusion.
      Congenital upper lid eversion is usually a benign condition which responds well
      to conservative treatment. Creating awareness amongst healthcare professionals is
      essential. 

PMID- 25960904
TI  - Patellar Tendon Rupture after Lateral Release without Predisposing Systemic
      Disease or Steroid Use.
AB  - Arthroscopic technique for lateral release is the most widely used procedure for
      the correction of recurrent dislocations of the patella. In the relevant
      literature, several complications of lateral release are described, but the
      spontaneous patellar tendon rupture has never been suggested as a possible
      complication of this surgical procedure. Patellar tendon rupture is a rather
      infrequent and often unilateral lesion. Nevertheless, in case of systemic
      diseases (LES, rheumatoid arthritis, and chronic renal insufficiency) that can
      weaken collagen structures, bilateral patellar tendon ruptures are described. We
      report a case of a 24-year-old girl with spontaneous rupture of patellar tendon
      who, at the age of 16, underwent an arthroscopic lateral release for recurrent
      dislocation of the patella. This is the first case of described spontaneous
      patellar tendon rupture that occurred some years after an arthroscopic lateral
      release. 

PMID- 25960905
TI  - Congenital cholesteatoma localized to the mastoid cavity and presenting as a
      mastoid abscess.
AB  - Introduction. Congenital cholesteatoma is a pearly white mass that rarely
      originates from the mastoid process. Case Report. A 21-year-old male patient
      presented to our department with severe right mastoid pain and postauricular
      fluctuant swelling for 23 days. There was no preceding history of ear complaints
      and examination showed a normal right ear drum. Emergency exploration of the
      mastoid process was done on the same day and revealed localized cholesteatoma
      limited only to the mastoid cavity. Conclusion. Despite a rarity, the mastoid
      process should be always put in mind as a site of origin for congenital
      cholesteatoma. 

PMID- 25960907
TI  - Microsatellite Genotyping to Distinguish Somatic beta-HCG Secreting Carcinoma
      from Epithelioid Trophoblastic Tumor.
AB  - Objective. Morphologically, beta-HCG secreting somatic carcinoma can be difficult
      to distinguish from epithelioid trophoblastic tumors (ETT). However, their
      distinction is critical due to their potentially differing prognoses and choice
      of chemotherapy. Presence of biparental alleles in ETT can be identified with
      molecular testing. We describe a patient who presented with metastatic carcinoma
      and elevated serum beta-HCG and contrast this to an ETT in another patient. Data
      and Results. A 32-year-old female with recent possible miscarriage presented with
      pulmonary emboli and was found to have an increased serum beta-HCG, a
      retroduodenal mass, and multiple nodules in her lungs, liver, and para-aortic
      lymph nodes. Biopsy showed a beta-HCG and p63 positive epithelioid neoplasm with
      otherwise noncontributory immunohistochemistry. Molecular testing for biparental
      alleles in repeated length polymorphisms was negative, consistent with somatic
      origin. The second patient was a 35-year-old pregnant female with increased serum
      beta-HCG and a uterine epithelioid tumor positive for beta-HCG. Clinical and
      pathologic findings were characteristic of ETT and molecular testing was not
      required. These 2 cases illustrate that beta-HCG secreting tumors of different
      etiologies may have similar appearances, and when clinical and/or IHC findings
      are inconclusive, molecular testing may be useful. 

PMID- 25960906
TI  - Extramedullary hematopoiesis in a sentinel lymph node as an early sign of chronic
      myelomonocytic leukemia.
AB  - Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic malignancy with
      features of both a myeloproliferative neoplasm and a myelodysplastic syndrome.
      Even though extramedullary leukemic infiltration is common in CMML patients,
      lymph node involvement has rarely been reported in the literature. We present an
      unusual case of a 72-year-old female who was found to have extramedullary
      hematopoiesis (EMH) in a sentinel lymph node that was excised during mastectomy
      for lobular breast carcinoma. One year later bone marrow biopsy was performed due
      to persistent anemia, thrombocytopenia, and monocytosis and the patient was
      diagnosed with CMML. Our case illustrates the importance of recognizing EMH in a
      lymph node during routine histological examination, especially in adults.
      Proliferation of bone marrow elements in a lymph node, in a patient with no known
      hematologic disorder, should trigger immediate bone marrow evaluation, as this
      could be the first clue in diagnosing underlying bone marrow disorder. 

PMID- 25960908
TI  - Successful treatment of bronchial fistula after pulmonary lobectomy by
      endobronchial embolization using an endobronchial watanabe spigot.
AB  - A bronchial fistula is one of the most serious complications that can occur
      following pulmonary lobectomy. We herein report a case of bronchial fistula that
      was successfully treated by endobronchial embolization using an Endobronchial
      Watanabe Spigot (EWS). A 72-year-old male underwent right lower lobectomy of the
      lung with nodal dissection for a pulmonary squamous cell carcinoma. A bronchial
      fistula developed 53 days after surgery. Tube drainage was performed, and air
      leakage was apparent. Under endoscopic observation, intrathoracic injection of
      indigo carmine revealed that a fistula existed at the peripheral site of the
      B(2)ai bronchus. After one EWS (small) was inserted into the B(2)a bronchus
      tightly using a bronchoscope, the air leakage was stopped. Pleurodesis was
      further carried out, the thoracostomy tube was subsequently removed, and the
      patient was discharged. Endobronchial embolization using an EWS is an option for
      the treatment of a bronchial fistula after pulmonary resection. 

PMID- 25960909
TI  - Pulmonary nocardiosis in an immunocompetent patient with cystic fibrosis.
AB  - Nocardia spp. are bacteria of low virulence that cause infection classically in
      immunocompromised hosts with the lungs as the primary site of infection in the
      majority of cases. Patients with cystic fibrosis have pulmonary disease
      characterized by frequent and progressive bacterial infections. Reports of
      Nocardia spp. isolation in CF are rare in the literature and may represent
      colonization or active infection, the significance and optimal treatment of which
      are unknown. We report the second case to date of Nocardia transvalensis
      pulmonary infection in an immunocompetent patient with CF and the first in a
      child under the age of eighteen. 

PMID- 25960910
TI  - Spectrum of surgical presentation of eosinophilic enteritis.
AB  - Eosinophilic enteritis is a rare disorder presenting mostly with diarrhea,
      malabsorption, abdominal pain, weight loss, and hypersensitivity. Surgical
      manifestation of eosinophilic gastrointestinal disorders depends on the site and
      extent of involvement. In our case series of four patients two of them had
      ileocaecal masses with recurrent subacute intestinal obstruction with past
      history of intake of antitubercular drugs for 9 months. On histopathological
      examination both of them proved to have eosinophilic enterocolitis. Thus it is a
      clinical dilemma to differentiate between these two conditions. The other two
      patients presented as acute abdomen with perforation and intussusception. All
      four patients were treated surgically. Postoperatively they recovered well with
      no symptoms on one year follow-up. In Indian setup tuberculosis being rampant
      there may be under reporting or wrongly diagnosed cases of eosinophilic
      enteritis. Thus a strong clinical suspicion and awareness of this clinical entity
      are essential among surgical community. 

PMID- 25960911
TI  - Robotic total pelvic exenteration with laparoscopic rectus flap: initial
      experience.
AB  - Total pelvic exenteration is a highly morbid procedure performed for locally
      advanced pelvic malignancies. We describe our experience with three patients who
      underwent robotic total pelvic exenteration with laparoscopic rectus flap and
      compare perioperative characteristics to our open experience. Demographic, tumor,
      operative, and perioperative factors were examined with descriptive statistics
      reported. Mean operative times were similar between the two groups. When compared
      to open total pelvic exenteration cases (n = 9), median estimated blood loss, ICU
      stay, and hospital stay were all decreased. These data show robotic pelvic
      exenteration with laparoscopic rectus flap is technically feasible. The surgery
      was well tolerated with low blood loss and comparable operative times to the open
      surgery. Further study is needed to confirm the oncologic efficacy and the
      suggested improvement in surgical morbidity. 

PMID- 25960912
TI  - Hafnia alvei Urosepsis in a Kidney Transplant Patient.
AB  - Hafnia alvei, a gram-negative facultative anaerobic, rod-shaped bacterium, is a
      rare cause of infection in humans. We report on a renal transplant patient who
      developed H. alvei pyelonephritis and urosepsis. The source of infection remains
      enigmatic but is most likely the intestinal tract. Appropriate antibiotic therapy
      with cefepime followed by oral ciprofloxacin brought about rapid resolution of
      symptoms and complete recovery. H. alvei may cause severe infection in transplant
      patients without predisposing factors such as hospitalization, invasive
      procedures, or antibiotic treatment. 

PMID- 25960913
TI  - Dedifferentiated paratesticular liposarcoma with osseous metaplasia.
AB  - Paratesticular liposarcoma is a rare tumour of the genitourinary track but the
      most common of all sarcomas in adults. The dedifferentiated variation occurs only
      in 10% of liposarcoma cases. The typical clinical presentation is similar to an
      inguinal hernia or a benign lipoma. We present the case of a dedifferentiated
      paratesticular liposarcoma with osseous metaplasia of the spermatic cord, in a
      male presented with acute scrotum. 

PMID- 25960914
TI  - Dialysis arteriovenous fistula causing subclavian steal syndrome in the absence
      of subclavian artery stenosis.
AB  - We present a rare cause of subclavian steal syndrome secondary to a dialysis
      arteriovenous fistula (AVF). A 69-year-old female with end-stage renal disease
      presented with ataxia and recurrent fainting spells. Angiography revealed normal
      subclavian arteries bilaterally, a right VA origin occlusion, and an apparent
      left VA origin occlusion. However, carotid artery angiography demonstrated flow
      through the posterior communicating artery with retrograde filling of the basilar
      artery and left VA to its subclavian origin. Repeat left subclavian arteriography
      during external compression of the AVF demonstrated normal antegrade left VA
      flow. The AVF was subsequently ligated resulting in complete symptom resolution. 

PMID- 25960915
TI  - Medial clavicular osteophyte: a novel cause of paget-schroetter syndrome.
AB  - Paget-Schroetter syndrome is a form of upper limb deep venous thrombosis usually
      seen in younger patients in association with repetitive activities of the
      affected limb. When occurring in more elderly patients or in those where it is
      difficult to appreciate a causative mechanism, other aetiologies should be
      considered. We present a case in which degenerative osteoarthritis of the
      sternoclavicular joint with osteophyte development impinged on the subclavian
      vein, leading to extensive upper limb thrombosis. The difficulties in identifying
      and managing this unusual cause of Paget-Schroetter are presented and discussed. 

PMID- 25960917
TI  - A community-based gastroenteritis outbreak after Typhoon Haiyan, Leyte,
      Philippines, 2013.
AB  - BACKGROUND: Three weeks after Typhoon Haiyan, an increasing number of acute
      gastroenteritis cases were reported in Kananga, Leyte, an area where evacuated
      residents had returned home two days after the disaster. An outbreak
      investigation was conducted to identify the source and risk factors associated
      with the increase of gastroenteritis. METHODS: A case was defined as any person
      in Kananga who developed acute diarrhoea (>= 3 times/24 hours) and any of the
      following symptoms: fever, nausea, vomiting or abdominal pain from 11 November
      2013 to 10 December 2013. Active case finding was conducted by reviewing medical
      records, and a case-control study was conducted. Rectal swabs and water samples
      were tested for bacteriological examination. RESULTS: One hundred and five cases
      were identified. Multivariate analysis revealed that consumption of untreated
      drinking-water was associated with illness (adjusted odds ratio: 18.2). Both
      rectal swabs and municipal water samples tested positive for Aeromonas
      hydrophila. On inspection of the municipal water system, breaks in the
      distribution pipes were found with some submerged in river water. CONCLUSION:
      This acute gastroenteritis outbreak was most likely caused by Aeromonas
      hydrophila and transmitted through a contaminated water source. This study
      highlights that areas less damaged by a disaster that do not require ongoing
      evacuation centres can still have acute gastroenteritis outbreaks. All affected
      areas should be monitored during a disaster response, not just those with
      evacuation centres. Boiling or chlorinating of water should also be recommended
      for all areas affected by disaster.

PMID- 25960916
TI  - Neurophysiology of Drosophila models of Parkinson's disease.
AB  - We provide an insight into the role Drosophila has played in elucidating
      neurophysiological perturbations associated with Parkinson's disease- (PD-)
      related genes. Synaptic signalling deficits are observed in motor, central, and
      sensory systems. Given the neurological impact of disease causing mutations
      within these same genes in humans the phenotypes observed in fly are of
      significant interest. As such we observe four unique opportunities provided by
      fly nervous system models of Parkinson's disease. Firstly, Drosophila models are
      instrumental in exploring the mechanisms of neurodegeneration, with several PD
      related mutations eliciting related phenotypes including sensitivity to energy
      supply and vesicular deformities. These are leading to the identification of
      plausible cellular mechanisms, which may be specific to (dopaminergic) neurons
      and synapses rather than general cellular phenotypes. Secondly, models show
      noncell autonomous signalling within the nervous system, offering the opportunity
      to develop our understanding of the way pathogenic signalling propagates,
      resembling Braak's scheme of spreading pathology in PD. Thirdly, the models link
      physiological deficits to changes in synaptic structure. While the structure
      function relationship is complex, the genetic tractability of Drosophila offers
      the chance to separate fundamental changes from downstream consequences. Finally,
      the strong neuronal phenotypes permit relevant first in vivo drug testing. 

PMID- 25960918
TI  - Tuberculosis case notification data in Viet Nam, 2007 to 2012.
AB  - Tuberculosis (TB) remains a major cause of morbidity and mortality, and Viet Nam
      ranks 12 among the 22 high-TB burden countries. This study analyses surveillance
      data of the National Tuberculosis Control Programme in Viet Nam for the six-year
      period 2007 to 2012. During the study period, 598,877 TB cases (all forms) were
      notified, and 313,225 (52.3%) were new smear-positive cases. The case
      notification rate of new smear-positive cases was decreased, from 65 per 100,000
      population in 2007 to 57 per 100,000 population in 2012; this decrease was
      observed for males and females in all age groups except males aged 0-14 and
      females aged 15-24 years. The male-to-female ratio of new smear-positive TB cases
      increased from 2.85 in 2007 to 3.02 in 2012. The average annual cure rate of new
      smear-positive cases was 90.3%. The high male-to-female ratio for new smear
      positive TB cases in this notification data was lower than that from the 2007 TB
      prevalence survey in Viet Nam, suggesting a lower case detection for males. The
      decrease in new smear-positive case notification rates may reflect a decline in
      TB incidence in Viet Nam as several programmatic improvements have been made,
      although further research is required to increase case detection among young
      males and children.

PMID- 25960919
TI  - Tuberculosis case-finding in Cambodia: analysis of case notification data, 2000
      to 2013.
AB  - The routine tuberculosis (TB) surveillance system in Cambodia has been
      strengthened under the National TB Programme (NTP). This paper provides an
      overview of the TB surveillance data for Cambodia at the national level for the
      period 2000 to 2013 and at the subnational level for 2013. The proportion of the
      total population that were screened for TB rose from 0.4% in 2001 to 1.1% in
      2013, while the smear-positivity rate decreased from 28.9% to 8.1% in the same
      period. The total number of notified TB cases increased steadily from 2000; this
      has stabilized in recent years with 39 055 cases notified in 2013. The proportion
      of all TB cases that were smear-positive decreased from 78% in 2000 to 36% in
      2013. Case notification rates (CNRs) for all forms of TB and new smear-positive
      TB in 2013 were 261 and 94 per 100 000 population, respectively. Higher CNRs were
      found in the north-western and south-eastern parts of the country and were higher
      for males especially in older age groups. The increase in TB screening, decline
      in the smear-positive rate and decline in notified smear-positive TB cases likely
      reflect a long-term positive impact of the NTP. A negative correlation between
      the proportion of the population screened and the smear-positivity rate at the
      subnational level helped identify where to find undiagnosed cases. Subnational
      differences in case notification of the elderly and in children provide more
      specific targets for case-finding and further encourage strategic resource
      allocation. 

PMID- 25960921
TI  - Intestinal parasites of children and adults in a remote Aboriginal community of
      the Northern Territory, Australia, 1994-1996.
AB  - INTRODUCTION: Parasitic infections can adversely impact health, nutritional
      status and educational attainment. This study investigated hookworm and other
      intestinal parasites in an Aboriginal community in Australia from 1994 to 1996.
      METHODS: Seven surveys for intestinal parasites were conducted by a quantitative
      formol-ether method on faecal samples. Serological testing was conducted for
      Strongyloides stercoralis and Toxocara canis IgG by enzyme-linked immunosorbent
      assays. RESULTS: Of the 314 participants, infections were as follows: Trichuris
      trichiura (86%); hookworm, predominantly Ancylostoma duodenale (36%); Entamoeba
      spp. (E. histolytica complex [E. histolytica, E. dispar and E. moskovski], E.
      coli and E. hartmanni) (25%); S. stercoralis (19%); Rodentolepis nana (16%); and
      Giardia duodenalis (10%). Serological diagnosis for 29 individuals showed that
      28% were positive for S. stercoralis and 21% for T. canis. There was a decrease
      in the proportion positive for hookworm over the two-year period but not for the
      other parasite species. The presence of hookworm, T. trichiura and Entamoeba spp.
      was significantly greater in 5-14 year olds (n = 87) than in 0-4 year olds (n =
      41), while the presence of S. stercoralis, R. nana, G. duodenalis and Entamoeba
      spp. in 5-14 year olds was significantly greater than 15-69 year olds (n = 91).
      DISCUSSION: Faecal testing indicated a very high prevalence of intestinal
      parasites, especially in schoolchildren. The decrease in percentage positive for
      hookworm over the two years was likely due to the albendazole deworming
      programme, and recent evidence indicates that the prevalence of hookworm is now
      low. However there was no sustained decrease in percentage positive for the other
      parasite species.

PMID- 25960920
TI  - Hospital preparedness for Ebola virus disease: a training course in the
      Philippines.
AB  - OBJECTIVE: To develop, teach and evaluate a training workshop that could rapidly
      prepare large numbers of health professionals working in hospitals in the
      Philippines to detect and safely manage Ebola virus disease (EVD). The strategy
      was to train teams (each usually with five members) of key health professionals
      from public, private and local government hospitals across the Philippines who
      could then guide Ebola preparedness in their hospitals. METHODS: The workshop was
      developed collaboratively by the Philippine Department of Health and the country
      office of the World Health Organization. It was evaluated using a pre- and post
      workshop test and two evaluation forms. chi(2) tests and linear regression
      analyses were conducted comparing pre- and post-workshop test results. RESULTS: A
      three-day workshop was developed and used to train 364 doctors, nurses and
      medical technologists from 78 hospitals across the Philippines in three initial
      batches. Knowledge about EVD increased significantly (P < 0.009) although
      knowledge on transmission remained suboptimal. Confidence in managing EVD
      increased significantly (P = 0.018) with 96% of participants feeling more
      prepared to safely manage EVD cases. DISCUSSION: The three-day workshop to
      prepare hospital staff for EVD was effective at increasing the level of knowledge
      about EVD and the level of confidence in managing EVD safely. This workshop could
      be adapted for use as baseline training in EVD in other developing countries to
      prepare large numbers of hospital staff to rapidly detect, isolate and safely
      manage EVD cases.

PMID- 25960922
TI  - Brief behavioural surveys in routine HIV sentinel surveillance: a new tool for
      monitoring the HIV epidemic in Viet Nam.
AB  - In this report we describe a new approach in HIV sentinel surveillance that was
      piloted in Viet Nam in 2009 and is currently being rolled out in all provinces.
      It comprises a brief behavioural questionnaire added to the HIV sentinel
      surveillance surveys conducted routinely among people who inject drugs, female
      sex workers and men who have sex with men. Timely reporting of data from this
      system has resulted in improvements to HIV prevention efforts for most at-risk
      populations. 

PMID- 25960923
TI  - Sexually transmitted infections among transgender people and men who have sex
      with men in Port Vila, Vanuatu.
AB  - Despite high sexually transmitted infection (STI) prevalence in the Pacific,
      there are limited data on STIs and risk among men who have sex with men (MSM) and
      transgender people (TG). In 2011, an Integrated Bio-Behavioural Survey recruited
      self-identified MSM and TG in Port Vila, Vanuatu. Descriptive findings were
      stratified by sexuality. Among 28 (55%) MSM and 23 (45%) TG, recent anal sex with
      male partners was more common among MSM (94% vs 71%; P < 0.1), including with
      casual (47% vs 35%), regular (59% vs 29%) and paying partners (28% vs 12%). MSM
      more commonly reported lifetime (P < 0.01) and recent sex with female partners (P
      < 0.01). Reported condom use with any partner type was low. More MSM (35%) than
      TG (24%) were diagnosed with an STI; previous treatment-seeking behaviour when
      symptomatic was lower among TG (P < 0.1). Tailored strategies acknowledging
      differences between MSM and TG are required to reduce STI vulnerability in
      Vanuatu.

PMID- 25960924
TI  - Identification of Enterovirus C105 for the first time in New Zealand.

PMID- 25960925
TI  - International Health Regulations (2005) facilitate communication for in-flight
      contacts of a Middle East respiratory syndrome case, Hong Kong Special
      Administrative Region, 2014.
AB  - The International Health Regulations (IHR) (2005) require World Health
      Organization Member States to notify events fulfilling two of four criteria: (1)
      serious public health impact; (2) unusual or unexpected event; (3) significant
      risk of international spread; or (4) significant risk of international travel or
      trade restrictions. (1) In-flight transmission of infections like severe acute
      respiratory syndrome is well documented. (2) With the enormous amount of air
      travel today, the risk of increasing in-flight transmission and subsequent
      international spread of infections are increasing. Prompt notification and
      information sharing under the IHR mechanism is critical for effective contact
      tracing and prompt control measures. We report on a case of in-flight exposure to
      an infection with significant public health risks that was successfully resolved
      using IHR (2005) guidelines. 

PMID- 25960926
TI  - Ebola preparedness in the Western Pacific Region, 2014.
AB  - West Africa is currently experiencing the largest outbreak of Ebola virus disease
      (EVD) in history with intense transmission in several affected countries. For non
      affected countries, the best protective measures are adequate levels of
      preparedness including vigilant surveillance to detect cases early and well
      prepared health systems to ensure rapid containment of the virus and to avoid
      further spread. The World Health Organization Regional Office for the Western
      Pacific recently conducted two activities: a web-based EVD preparedness survey
      and an EVD simulation exercise to determine the overall level of EVD preparedness
      in the Region. The survey and exercise together demonstrate there is a good
      overall level of preparedness for a potential imported case of EVD in the Western
      Pacific Region. However, several areas still require further strengthening before
      the Region can efficiently and effectively respond to potential EVD events,
      including laboratory testing arrangements; clinical management and infection
      prevention and control; and public health intervention measures, particularly at
      points of entry. Importantly, the survey and exercise also highlight the unique
      situation in Pacific island countries and emphasize that special considerations
      are needed to better support these countries in EVD preparedness. 

PMID- 25960928
TI  - Methylation Abnormalities in Mammary Carcinoma: The Methylation Suicide
      Hypothesis.
AB  - Promoter silencing by ectopic de novo methylation of tumor suppressor genes has
      been proposed as comparable or equivalent to inactivating mutations as a factor
      in carcinogenesis. However, this hypotheses had not previously been tested by
      high resolution, high-coverage whole-genome methylation profiling in primary
      carcinomas. We have determined the genomic methylation status of a series of
      primary mammary carcinomas and matched control tissues by examination of more
      than 2.7 billion CpG dinucleotides. Most of the tumors showed variable losses of
      DNA methylation from all sequence compartments, but increases in promoter
      methylation were infrequent, very small in extent, and were observed largely at
      CpG-poor promoters. De novo methylation at the promoters of proto-oncogenes and
      tumor suppressor genes occurred at approximately the same frequency. The findings
      indicate that tumor suppressor silencing by de novo methylation is much less
      common than currently believed. We put forward a hypothesis under which the
      demethylation commonly observed in carcinomas is a manifestation of a defensive
      system that kills incipient cancer cells.

PMID- 25960927
TI  - Oxidants and antioxidants: friends or foes?

PMID- 25960929
TI  - Comparison of Follicle-Stimulating Hormone Glycosylation Microheterogenity by
      Quantitative Negative Mode Nano-Electrospray Mass Spectrometry of Peptide-N
      Glycanase-Released Oligosaccharides.
AB  - Glycans from six highly purified hFSH preparations were released by peptide-N
      glycanase digestion and analyzed by negative mode nano-ESI mass spectrometry
      before and after neuraminidase digestion. Pituitary glycan structures were mainly
      high-mannose, di-, tri-, and tetra-antennary, and their abundance largely
      paralleled that reported by other investigators using different approaches. For
      most of the FSH preparations, the differences in glycosylation appeared to be
      restricted to relative abundances of the major glycan families, as defined by
      their neutral core oligosaccharide structures. Qualitative differences between
      glycan populations were largely relegated to those species that were lowest in
      abundance. Significant qualitative differences were noted in two cases.
      Recombinant GH3-hFSH triantennary glycans appeared to have the third antenna
      exclusively on the mannose6-branch, in contrast to all pituitary and urinary hFSH
      triantennary glycans, in which this antenna was exclusively attached to the
      mannose3-branch. The hypo-glycosylated hFSH preparation isolated from purified
      hLH was decorated with high mannose glycans that accounted for over 40% of the
      total in this population. As this preparation was found to be consistently 20
      fold more active than hFSH24 in FSH receptor-binding assays, it appears that both
      macroheterogeneity and microheterogeneity in FSH preparations need to be taken
      into account.

PMID- 25960930
TI  - IFNalpha signaling through PKC-theta is essential for antitumor NK cell function.
AB  - We have previously shown that the development of a major histocompatibility
      complex class I (MHC-I)-deficient tumor was favored in protein kinase C-theta
      knockout (PKC-theta-/-) mice compared to that occurring in wild-type mice. This
      phenomenon was associated with scarce recruitment of natural killer (NK) cells to
      the tumor site, as well as impaired NK cell activation and reduced cytotoxicity
      ex vivo. Poly-inosinic:cytidylic acid (poly I:C) treatment activated PKC-theta in
      NK cells depending on the presence of a soluble factor produced by a different
      splenocyte subset. In the present work, we sought to analyze whether interleukin
      15 (IL-15) and/or interferon-alpha (IFNalpha) mediate PKC-theta-dependent
      antitumor NK cell function. We found that IL-15 improves NK cell viability,
      granzyme B expression, degranulation capacity and interferon-gamma (IFNgamma)
      secretion independently of PKC-theta. In contrast, we found that IFNalpha
      improves the degranulation capability of NK cells against target cancer cells in
      a PKC-theta-dependent fashion both ex vivo and in vivo. Furthermore, IFNalpha
      induces PKC-theta auto-phosphorylation in NK cells, in a signal transduction
      pathway involving both phosphatidylinositol-3-kinase (PI3K) and phospholipase-C
      (PLC) activation. PKC-theta dependence was further implicated in IFNalpha-induced
      transcriptional upregulation of chemokine (C-X-C motif) ligand 10 (CXCL10), a
      signal transducer and activator of transcription-1 (STAT-1)-dependent target of
      IFNalpha. The absence of PKC-theta did not affect IFNalpha-induced STAT-1 Tyr701
      phosphorylation but affected the increase in STAT-1 phosphorylation on Ser727,
      attenuating CXCL10 secretion. This connection between IFNalpha and PKC-theta in
      NK cells may be exploited in NK cell-based tumor immunotherapy.

PMID- 25960931
TI  - Anti-p21 autoantibodies detected in colorectal cancer patients: A proof of
      concept study.
AB  - Whereas the presence of autoantibodies in cancer patients has been acknowledged,
      their diagnostic or therapeutic significance has yet to be established. This is
      due, at least in part, to the lack of robust screening techniques to detect and
      characterize such antibodies for further assessment. In this study, we screened
      colorectal cancer (CRC) patient sera for antibodies specifically targeting the
      key cell cycle inhibitory factor p21 encoded by the cyclin-dependent kinase
      inhibitor 1A (CDKN1A). Anti-p21 antibody titers were higher in CRC patient
      samples versus controls, correlating with a more advanced disease stage and lymph
      node involvement. Further, we isolated for the first time a specific human
      antibody fragment against p21, which could potentially be useful as a tool to
      study tumorigenicity in CRC patients.

PMID- 25960932
TI  - Metronomic cyclophosphamide enhances HPV16E7 peptide vaccine induced antigen
      specific and cytotoxic T-cell mediated antitumor immune response.
AB  - In clinical trials, metronomic cyclophosphamide (CPA) is increasingly being
      combined with vaccines to reduce tumor-induced immune suppression. Previous
      strategies to modulate the immune system during vaccination have involved
      continuous administration of low dose chemotherapy, studies that have posed
      unique considerations for clinical trial design. Here, we evaluated metronomic
      CPA in combination with a peptide vaccine targeting HPV16E7 in an HPV16-induced
      tumor model, focusing on the cytotoxic T-cell response and timing of low dose
      metronomic CPA (mCPA) treatment relative to vaccination. Mice bearing C3 tumors
      were given metronomic CPA on alternating weeks in combination with immunization
      with a DepoVax vaccine containing HPV16E749-57 peptide antigen every 3 weeks.
      Only the combination therapy provided significant long-term control of tumor
      growth. The efficacy of the vaccine was uncompromised if given at the beginning
      or end of a cycle of metronomic CPA. Metronomic CPA had a pronounced
      lymphodepletive effect on the vaccine draining lymph node, yet did not reduce the
      development of antigen-specific CD8+ T cells induced by vaccination. This
      enrichment correlated with increased cytotoxic activity in the spleen and
      increased expression of cytotoxic gene signatures in the tumor. Immunity could be
      passively transferred through CD8+ T cells isolated from tumor-bearing mice
      treated with the combinatorial treatment regimen. A comprehensive survey of
      splenocytes indicated that metronomic CPA, in the absence of vaccination, induced
      transient lymphodepletion marked by a selective expansion of myeloid-derived
      suppressor cells. These results provide important insights into the multiple
      mechanisms of metronomic CPA induced immune modulation in the context of a
      peptide cancer vaccine that may be translated into more effective clinical trial
      designs.

PMID- 25960933
TI  - Stress-related and homeostatic cytokines regulate Vgamma9Vdelta2 T-cell
      surveillance of mevalonate metabolism.
AB  - The potentially oncogenic mevalonate pathway provides building blocks for protein
      prenylation and induces cell proliferation and as such is an important
      therapeutic target. Among mevalonate metabolites, only isopentenyl pyrophosphate
      (IPP) has been considered to be an immunologically relevant antigen for primate
      specific, innate-like Vgamma9Vdelta2 T cells with antitumor potential. We show
      here that Vgamma9Vdelta2 T cells pretreated with the stress-related, inflammasome
      dependent cytokine interleukin 18 (IL-18) were potently activated not only by IPP
      but also by all downstream isoprenoid pyrophosphates that exhibit combined
      features of antigens and cell-extrinsic metabolic cues. Vgamma9Vdelta2 T cells
      induced this way effectively proliferated even under severe lymphopenic
      conditions and the antioxidant N-acetylcysteine significantly improved
      reconstitution of gammadelta T cells predominantly with a central memory
      phenotype. The homeostatic cytokine IL-15 induced the differentiation of effector
      cells in an antigen-independent fashion, which rapidly produced abundant
      interferon gamma (IFNgamma) upon antigen re-encounter. IL-15 induced effector
      gammadelta T cells displayed increased levels of the cytotoxic lymphocyte
      associated proteins CD56, CD96, CD161 and perforin. In response to stimulation
      with isoprenoid pyrophosphates, these effector cells upregulated surface
      expression of CD107a and exhibited strong cytotoxicity against tumor cells in
      vitro. Our data clarify understanding of innate immunosurveillance mechanisms and
      will facilitate the controlled generation of robust Vgamma9Vdelta2 T cell subsets
      for effective cancer immunotherapy.

PMID- 25960934
TI  - Spontaneous presence of FOXO3-specific T cells in cancer patients.
AB  - In the present study, we describe forkhead box O3 (FOXO3)-specific, cytotoxic
      CD8+ T cells existent among peripheral-blood mononuclear cells (PBMCs) of cancer
      patients. FOXO3 immunogenicity appears specific, as we did not detect reactivity
      toward FOXO3 among T cells in healthy individuals. FOXO3 may naturally serve as a
      target antigen for tumor-reactive T cells as it is frequently over-expressed in
      cancer cells. In addition, expression of FOXO3 plays a critical role in
      immunosuppression mediated by tumor-associated dendritic cells (TADCs). Indeed,
      FOXO3-specific cytotoxic T lymphocytes (CTLs) were able to specifically recognize
      and kill both FOXO3-expressing cancer cells as well as dendritic cells. Thus,
      FOXO3 was processed and presented by HLA-A2 on the cell surface of both immune
      cells and cancer cells. As FOXO3 programs TADCs to become tolerogenic, FOXO3
      signaling thereby comprises a significant immunosuppressive mechanism, such that
      FOXO3 targeting by means of specific T cells is an attractive clinical therapy to
      boost anticancer immunity. In addition, the natural occurrence of FOXO3-specific
      CTLs in the periphery suggests that these T cells hold a function in the complex
      network of immune regulation in cancer patients.

PMID- 25960935
TI  - Molecular mimicry of MAGE-A6 and Mycoplasma penetrans HF-2 epitopes in the
      induction of antitumor CD8+ T-cell responses.
AB  - A promising vaccine strategy for the treatment of cancer involves the use of
      vaccines incorporating tumor antigen-derived synthetic peptides that can be
      coordinately recognized by specific CD4+ and CD8+ T-cells. Previously, we
      reported that a MAGE-A6-derived peptide (MAGE-A6172-187) and its highly
      immunogenic and cross-reactive homolog derived from Mycoplasma penetrans HF-2
      permease (HF-2216-229) are promiscuously presented by multiple HLA-DR alleles to
      responder CD4+ T-cells obtained from healthy donors and melanoma patients. Here,
      we investigated whether these same peptides could concomitantly stimulate cross
      reactive MAGE-A6-specific CD8+ T-cell responses in vitro using cells isolated
      from HLA-A*0201 (HLA-A2)+ healthy individuals and patients with melanoma. We now
      show that MAGE-A6172-187 and, even more so, HF-2216-229, induce memory CD8+ T
      cells that recognize HLA-A2+ MAGE-A6+ tumor target cells. The immunogenicity of
      these peptides was at least partially attributed to their embedded MAGE-A6176-185
      and HF-2220-229 "homologous" sequences. The functional avidity of HF-2216-229
      peptide-primed CD8+ T cells for the MAGE-A6172-187 peptide was more than 100-fold
      greater than that of CD8+ T cells primed with the corresponding MAGE-A6 peptide.
      Additionally, these 2 peptides were recognized in interferon gamma (IFNgamma) and
      granzyme B ELISPOT assays by CD8+ T-cell clones displaying variable T-cell
      receptor (TCR) Vbeta usage. These data suggest that the immune cross-reactivity
      of the MAGE-A6172-187 and HF-2216-229 peptides extends to CD8+ T cells, at least
      in HLA-A2+ donors, and supports the potential translational utility of these
      epitopes in clinical vaccine formulations and for immunomonitoring of cancer
      patients.

PMID- 25960937
TI  - What Goes Around Comes Around ... Or Does It? Disrupting the Cycle of
      Traditional, Sport-Based Physical Education.
AB  - As typically taught, sport-based, multiactivity approaches to physical education
      provide students with few opportunities to increase their skill, fitness, or
      understanding. Alternative curriculum models, such as Sport Education, Teaching
      Games for Understanding, and Fitness for Life, represent a second generation of
      models that build on strong statements of democratic, student-centered practice
      in physical education. In the What Goes Around section of the paper, I discuss
      the U.S. perspective on the origins of alternative physical education curriculum
      models introduced in the early and mid-20th century as a response to sport and
      exercise programs of the times. Today, with the help of physical educators,
      scholars are conducting research to test new curricular alternatives or
      prototypes to provide evidence-based support for these models. Yet, the
      multiactivity, sport-based curriculum continues to dominate in most U.S. physical
      education classes. I discuss reasons for this dogged persistence and propose
      reforms to disrupt this pervasive pattern in the future.

PMID- 25960936
TI  - A catalog of HLA type, HLA expression, and neo-epitope candidates in human cancer
      cell lines.
AB  - Cancer cell lines are a tremendous resource for cancer biology and therapy
      development. These multipurpose tools are commonly used to examine the genetic
      origin of cancers, to identify potential novel tumor targets, such as tumor
      antigens for vaccine devel-opment, and utilized to screen potential therapies in
      preclinical studies. Mutations, gene expression, and drug sensitivity have been
      determined for many cell lines using next-generation sequencing (NGS). However,
      the human leukocyte antigen (HLA) type and HLA expression of tumor cell lines,
      characterizations necessary for the development of cancer vaccines, have remained
      largely incomplete and, such information, when available, has been distributed in
      many publications. Here, we determine the 4-digit HLA type and HLA expression of
      167 cancer and 10 non-cancer cell lines from publically available RNA-Seq data.
      We use standard NGS RNA-Seq short reads from "whole transcriptome" sequencing,
      map reads to known HLA types, and statistically determine HLA type,
      heterozygosity, and expression. First, we present previously unreported HLA Class
      I and II genotypes. Second, we determine HLA expression levels in each cancer
      cell line, providing insights into HLA downregulation and loss in cancer. Third,
      using these results, we provide a fundamental cell line "barcode" to track
      samples and prevent sample annotation swaps and contamination. Fourth, we
      integrate the cancer cell-line specific HLA types and HLA expression with
      available cell-line specific mutation information and existing HLA binding
      prediction algorithms to make a catalog of predicted antigenic mutations in each
      cell line. The compilation of our results are a fundamental resource for all
      researchers selecting specific cancer cell lines based on the HLA type and HLA
      expression, as well as for the development of immunotherapeutic tools for novel
      cancer treatment modalities.

PMID- 25960939
TI  - Impulsivity: present during euthymia in bipolar disorder? - a systematic review.
AB  - Because impulsivity is part of the presentation of bipolar disorder (BD) and is
      associated with its course, this systematic review presents the evidence whether
      increased impulsivity is present in a stable, euthymic mood and therefore
      potentially a vulnerability marker for BD. A multi-faceted model of impulsivity
      was adopted to explore how different facets may relate differently to BD. The
      evidence was explored in relation to studies employing measures of trait
      impulsivity (in self-report format) and studies exploring impulsivity with
      behavioural paradigms. Behavioural paradigms were separated into studies
      measuring response inhibition and those measuring the ability to delay
      gratification. Twenty-three papers met the inclusion criteria. Most studies using
      self-report measures found significant differences between euthymic BD patients
      and healthy controls. There was little evidence of increased impulsivity as
      measured by behavioural paradigms. Most studies found no significant difference
      in response inhibition between groups, though it is possible that much of the
      literature in this area was underpowered to detect an effect. Only five studies
      explored delay of gratification, of which the two methodologically strongest
      studies found no group differences. In conclusion, there is evidence that
      euthymic patients with BD report increased impulsivity when using self-ratings.
      However, there is currently limited evidence of impulsivity on behavioural
      measures assessing response inhibition, and this might be restricted to more
      severe cases. More research is needed on the ability to delay gratification
      before drawing any conclusions. However, to establish facets of impulsivity as
      vulnerability markers, future studies should include at-risk individuals to
      evaluate whether self-rated or behavioural impulsivity precedes the onset of BD. 

PMID- 25960938
TI  - Bridging Levels of Understanding in Schizophrenia Through Computational Modeling.
AB  - Schizophrenia is an illness with a remarkably complex symptom presentation that
      has thus far been out of reach of neuroscientific explanation. This presents a
      fundamental problem for developing better treatments that target specific
      symptoms or root causes. One promising path forward is the incorporation of
      computational neuroscience, which provides a way to formalize experimental
      observations and, in turn, make theoretical predictions for subsequent studies.
      We review three complementary approaches: (a) biophysically based models
      developed to test cellular-level and synaptic hypotheses, (b) connectionist
      models that give insight into large-scale neural-system-level disturbances in
      schizophrenia, and (c) models that provide a formalism for observations of
      complex behavioral deficits, such as negative symptoms. We argue that harnessing
      all of these modeling approaches represents a productive approach for better
      understanding schizophrenia. We discuss how blending these approaches can allow
      the field to progress toward a more comprehensive understanding of schizophrenia
      and its treatment.

PMID- 25960940
TI  - On the Development of Implicit and Control Processes in Relation to Substance Use
      in Adolescence.
AB  - Adolescence is a period in which brain structures involved in motivation and
      cognitive control continue to develop and also a period in which many youth begin
      substance use. Dual-process models propose that, among substance users, implicit
      or automatically activated neurocognitive processes gain in relative influence on
      substance use behavior, while the influence of cognitive control or reflective
      processes weakens. There is evidence that a variety of implicit cognitive
      processes, such as attentional bias, biased action tendencies (approach bias),
      memory bias and at a neural level, cue reactivity, are associated with adolescent
      substance use. The impact of these implicit processes on the further development
      of addictive behaviors appears to depend on moderating factors, such as
      (premorbid) executive control functions. Clear negative effects of adolescent
      substance use on executive control functions generally have not been found using
      behavioral tasks, although some studies have identified subtle and specific
      effects on cognitive functioning.

PMID- 25960941
TI  - Update on the Epidemiology and Prevention of HIV/AIDS in the United States.
AB  - This update on the epidemiology and prevention of HIV in the United States is
      intended to provide contextual background that will help inform an understanding
      of recent developments in the domestic HIV epidemic. We describe the epidemiology
      of HIV disease in the US and the HIV continuum of care based on data collected
      primarily through HIV surveillance systems led by the Centers for Disease Control
      and Prevention including HIV incidence, prevalence, comorbidities and death.
      Populations and geographic regions disparately impacted by HIV are also
      highlighted. The HIV prevention armamentarium is also described including
      behavioral approaches to prevention, the emerging availability of biomedical
      prevention interventions such as pre-exposure prophylaxis, and structural and
      population-level interventions including treatment as prevention. Finally gaps in
      our understanding of the epidemic are underscored and suggestions for future
      epidemiologic research are proposed.

PMID- 25960942
TI  - Preventing Cryptococcosis-Shifting the Paradigm in the Era of Highly Active
      Antiretroviral Therapy.
AB  - Cryptococcosis remains a significant cause of morbidity and mortality among HIV
      infected patients, especially in sub-Saharan Africa where it causes up to 20 % of
      AIDS-related deaths in HIV programs. A new, highly sensitive, and affordable
      point of care diagnostic test for cryptococcal infection, the lateral flow assay,
      can detect early sub-clinical cryptococcosis especially in areas with limited
      laboratory infrastructure. With a prevalence of detectable sub-clinical
      cryptococcal infection averaging 7.2 % (95 % CI 6.8-7.6 %) among 36 cohorts with
      CD4 <100 cells/MUL in Africa, together with data showing that preemptive
      fluconazole prevents overt cryptococcal disease in this population, implementing
      a screen and treat strategy as part of HIV care practice among patients with CD4
      <100 cells/MUL could prevent the incidence of often fatal cryptococcal meningitis
      in the setting of the HIV pandemic.

PMID- 25960943
TI  - The Epigenetic Effects of Prenatal Cadmium Exposure.
AB  - Prenatal exposure to the highly toxic and common pollutant cadmium has been
      associated with adverse effects on child health and development. However, the
      underlying biological mechanisms of cadmium toxicity remain partially unsolved.
      Epigenetic disruption due to early cadmium exposure has gained attention as a
      plausible mode of action, since epigenetic signatures respond to environmental
      stimuli and the fetus undergoes drastic epigenomic rearrangements during
      embryogenesis. In the current review, we provide a critical examination of the
      literature addressing prenatal cadmium exposure and epigenetic effects in human,
      animal, and in vitro studies. We conducted a PubMed search and obtained eight
      recent studies addressing this topic, focusing almost exclusively on DNA
      methylation. These studies provide evidence that cadmium alters epigenetic
      signatures in the DNA of the placenta and of the newborns, and some studies
      indicated marked sexual differences for cadmium-related DNA methylation changes.
      Associations between early cadmium exposure and DNA methylation might reflect
      interference with de novo DNA methyltransferases. More studies, especially those
      including environmentally relevant doses, are needed to confirm the
      toxicoepigenomic effects of prenatal cadmium exposure and how that relates to the
      observed health effects of cadmium in childhood and later life. 

PMID- 25960944
TI  - A mixed methods study of health and social disparities among substance-using
      African American/Black men who have sex with men.
AB  - African American/Black men who have sex with men (MSM) in the U.S. experience
      health and social disparities at greater rates than MSM of other
      races/ethnicities, including HIV infection and substance use. This mixed methods
      paper presents: 1) a quantitative examination of health and social disparities
      among a sample of substance-using African American/Black MSM (N=108), compared to
      Caucasian/White MSM (N=250), and 2) in-depth qualitative data from a subsample of
      African American/Black MSM (N=21) in order to contextualize the quantitative
      data. Findings indicate that compared to Caucasian/White MSM, African
      American/Black MSM experienced a wide range of health and social disparities
      including: substance use and dependence; buying, trading or selling sex;
      educational attainment; employment; homelessness; identifying as gay; HIV status;
      arrest history; social support; and satisfaction with one's living situation.
      Qualitative data suggests that structural interventions that address homophobia
      and the social environment would be likely to mitigate many of the health and
      social disparities experienced by African American/Black MSM.

PMID- 25960945
TI  - A Model of Cancer Clinical Trial Decision-making Informed by African-American
      Cancer Patients.
AB  - BACKGROUND: Clinical trials are critical to advancing cancer treatment. Minority
      populations are underrepresented among trial participants, and there is limited
      understanding of their decision-making process and key determinants of decision
      outcomes regarding trial participation. METHODS: To understand research decision
      making among clinical trial-eligible African-American cancer patients at Johns
      Hopkins, we conducted seven focus groups (n=32) with trial-offered patients >= 18
      years diagnosed with lung, breast, prostate, or colorectal cancer <= 5 years.
      Three "acceptor" and four "decliner" focus groups were conducted. Questions
      addressed: attitudes towards clinical trials, reasons for accepting or declining
      participation, and recommendations to improve minority recruitment and
      enrollment. Data were transcribed and analyzed using traditional approaches to
      content and thematic analysis in NVivo 9.0. Data coding resulted in themes that
      supported model construction. RESULTS: Participant experiences revealed the
      following themes when describing the decision-making process: Information
      gathering, Intrapersonal perspectives, and Interpersonal influences. Decision
      outcomes included the presence or absence of decision regret and satisfaction.
      From these themes, we generated a Model of Cancer Clinical Trial Decision-making.
      CONCLUSION: Our model should be tested in hypothesis-driven research to elucidate
      factors and processes influencing decision balance and outcomes of trial-related
      decision-making. The model should also be tested in other disparities populations
      and for diagnoses other than cancer.

PMID- 25960946
TI  - Cerebrospinal fluid inflammatory markers in patients with Listeria monocytogenes
      meningitis.
AB  - BACKGROUND: Listeria monocytogenes meningitis is the third most common cause of
      bacterial meningitis and is associated with high rates of mortality and
      unfavorable outcome. METHODS: We analyzed 101 cytokines, chemokines and
      complement factors in CSF of adult patients with Listeria meningitis included in
      a prospective cohort study and compared these biomarkers between Listeria
      meningitis patients and negative controls, and between Listeria meningitis
      patients with a favorable and an unfavorable outcome. RESULTS: CSF was available
      from 26 of 62 (42%) Listeria meningitis patients and 19 negative controls.
      Fifteen (58%) Listeria meningitis patients had an unfavorable outcome. In
      Listeria meningitis CSF levels of 51 biomarkers were significantly elevated
      compared to negative controls after Bonferroni correction. The 11 most
      significantly elevated (P < .01) biomarkers of unfavorable outcome in Listeria
      meningitis were markers of T-cell activation (sIL-2Ralpha, sCD40L and IL-1),
      interferon-related (IFN-alpha2, IL-18, CX3CL1, CCL20), markers of complement
      activation (C3a), and endothelial growth factor related (VEGF, CXCL7).
      CONCLUSIONS: Our data suggest that T-cell activation, complement activation,
      interferon- and endothelial growth factor production are important in the immune
      response to Listeria meningitis, and thereby influence outcome. GENERAL
      SIGNIFICANCE: Our study provides target pathways for further studies in the
      pathophysiology of Listeria meningitis.

PMID- 25960947
TI  - DNA methylation regulates neurophysiological spatial representation in memory
      formation.
AB  - Epigenetic mechanisms including altered DNA methylation are critical for altered
      gene transcription subserving synaptic plasticity and the retention of learned
      behavior. Here we tested the idea that one role for activity-dependent altered
      DNA methylation is stabilization of cognition-associated hippocampal place cell
      firing in response to novel place learning. We observed that a behavioral
      protocol (spatial exploration of a novel environment) known to induce hippocampal
      place cell remapping resulted in alterations of hippocampal Bdnf DNA methylation.
      Further studies using neurophysiological in vivo single unit recordings revealed
      that pharmacological manipulations of DNA methylation decreased long-term but not
      short-term place field stability. Together our data highlight a role for DNA
      methylation in regulating neurophysiological spatial representation and memory
      formation.

PMID- 25960948
TI  - SLC26A4 mutation testing for hearing loss associated with enlargement of the
      vestibular aqueduct.
AB  - Pendred syndrome (PS) is characterized by autosomal recessive inheritance of
      goiter associated with a defect of iodide organification, hearing loss,
      enlargement of the vestibular aqueduct (EVA), and mutations of the SLC26A4 gene.
      However, not all EVA patients have PS or SLC26A4 mutations. Two mutant alleles of
      SLC26A4 are detected in 1/4 of North American or European EVA populations, one
      mutant allele is detected in another 1/4 of patient populations, and no mutations
      are detected in the other 1/2. The presence of two mutant alleles of SLC26A4 is
      associated with abnormal iodide organification, increased thyroid gland volume,
      increased severity of hearing loss, and bilateral EVA. The presence of a single
      mutant allele of SLC26A4 is associated with normal iodide organification, normal
      thyroid gland volume, less severe hearing loss and either bilateral or unilateral
      EVA. When other underlying correlations are accounted for, the presence of a
      cochlear malformation or the size of EVA does not have an effect on hearing
      thresholds. This is consistent with observations of an Slc26a4 mutant mouse model
      of EVA in which hearing loss is independent of endolymphatic hydrops or inner ear
      malformations. Segregation analyses of EVA in families suggest that the patients
      carrying one mutant allele of SLC26A4 have a second, undetected mutant allele of
      SLC26A4, and the probability of a sibling having EVA is consistent with its
      segregation as an autosomal recessive trait. Patients without any mutations are
      an etiologically heterogeneous group in which siblings have a lower probability
      of having EVA. SLC26A4 mutation testing can provide prognostic information to
      guide clinical surveillance and management, as well as the probability of EVA
      affecting a sibling.

PMID- 25960949
TI  - Persimmon vinegar ripening with the mountain-cultivated ginseng ingestion reduces
      blood lipids and lowers inflammatory cytokines in obese adolescents.
AB  - PURPOSE: This study investigated the effect of the vinegar, which is made of 4
      year-old mountain-cultivated ginseng ripened into 4-year-matured persimmon
      vinegar, on the blood lipids level and inflammatory cytokines concentration in
      obese female adolescents. METHODS: Subjects ingested the vinegar, so-called
      'mountain-cultivated ginseng persimmon vinegar (MPV)', without meals every day
      for 6 weeks with activities control. Subjects were grouped into control (CON),
      persimmon vinegar (PV), and MPV with 10 people in each group. Blood lipids,
      triglyceride (TG), total-cholesterol (TC), and high density lipoprotein
      cholesterol (HDL-C) were analyzed. Also, glutamic oxaloacetic transaminase (GOT)
      and glutamate pyruvate transaminase (GPT) were analyzed for the hepatotoxicity.
      Blood cytokines, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha),
      and nuclear factor kappa-light-chain-enhancer of activated B cells (NFkappaB)
      were analyzed. RESULTS: Subjects showed a high reduction in body weight and body
      fat. Their blood lipid level was effectively improved, and the secretion of
      inflammatory cytokine was suppressed as well, except for TNF-alpha. However, the
      change ratio of the cytokines was high in PV and MPV. Such results were similar
      to those from research subjects who took persimmon vinegar only (PV), but the
      effect of the vinegar (MPV) was more remarkable. Besides, this mixture was found
      to have no effect on the hepatotoxicity. CONCLUSION: The significance of this
      study is that all the experiments were conducted without controlling research
      subjects' daily lives, and it is suggested that the vinegar may be recommended as
      a kind of health supplement food to suppress obesity. Especially, since these two
      products are traditional foods of Korean people, which have been taken for ages,
      it is expected that the fusing of two foods may be better applied to ordinary
      people who are concerned about obesity.

PMID- 25960950
TI  - Treadmill exercise after social isolation increases the levels of NGF, BDNF, and
      synapsin I to induce survival of neurons in the hippocampus, and improves
      depression-like behavior.
AB  - PURPOSE: We investigated the effects of 8 weeks of treadmill exercise on nerve
      growth factor (NGF), brain-derived neurotrophic factor (BDNF), and synapsin I
      protein expression and on the number of 5-bromo-2'-deoxyuridine-5'-mono-phosphate
      (BrdU)-positive cells in the dentate gyrus of the hippocampus in socially
      isolated rats. Additionally, we examined the effects of exercise on the number of
      serotonin (5-HT)- and tryptophan hydroxylase (TPH)-positive cells in the raphe
      nuclei and on depression behaviors induced by social isolation. METHODS: Forty
      male Sprague-Dawley rats were divided into four groups: (1) group housing and
      control group (GCG, n = 10); (2) group housing and exercise group (GEG, n = 10);
      (3) isolated housing and control group (ICG, n = 10); and (4) isolated housing
      and exercise group (IEG, n = 10). After 1 week of housing under the normal
      condition of 3 animals per cage, rats were socially isolated via transfer to
      individual cages for 8 weeks. Rats were then subjected to treadmill exercise for
      5 days per week for 8 weeks during which time the speed of the treadmill was
      gradually increased. RESULTS: Compared to the GCG, levels of NGF, BDNF, and
      synapsin I were significantly decreased in the ICG and significantly increased in
      the IEG (p < 0.001 respectively). Significantly more BrdU-positive cells in the
      GEG were present as compared to the GCG and ICG, and more BrdU-positive cells
      were found in the IEG as compared to the ICG (p < 0.001). 5-HT-positive cells in
      the GEG were significantly increased compared to the GCG and ICG, and more of
      these cells were found in the IEG as compared to the ICG (p < 0.01). TPH-positive
      cells in the GEG were significantly increased compared to those in the GCG and
      ICG (p < 0.05). In the forced swim test, immobility time was significantly
      increased in the ICG and significantly decreased in the IEG as compared to the
      ICG (p < 0.01). CONCLUSION: These results showed that regular treadmill exercise
      following social isolation not only increased the levels of NGF, BDNF, and
      synapsin I to induce survival of neurons in the hippocampus but also improved
      depression by increasing the number of serotonergic cells in the raphe nuclei.

PMID- 25960951
TI  - The effect of muscle power training with elastic band on blood glucose, cytokine,
      and physical function in elderly women with hyperglycemia.
AB  - PURPOSE: The purpose of this study was to identify the effects of muscle power
      training with elastic band on body composition, glucose relation factor, and
      physical function in elderly women with hyperglycemia. METHODS: A total of 16
      elderly women volunteered to participate in this study as subjects, and they were
      randomly assigned into one of the following two groups: muscle power training
      group (MPT: n = 8) and control group (CON: n = 8). The muscle power training
      group took exercise program using elastic band for 12 weeks, and the other group
      did not receive any exercise program during the same period. Before and after the
      experiment, both of the two groups received measurement in body composition (BMI,
      %Fat, skeletal muscle mass), glucose, cytokine (interleukin 6, adiponectin), and
      physical function (IPPB, grip strength). With these methods, the following
      conclusions were achieved. RESULTS: The results showed significant increases in
      adiponectin (p = 0.006), interleukin 6 (p = 0.018), SPPB (p = 0.024), and grip
      strength (P=.014). Blood glucose was significantly decreased in exercise group
      than contruo group. CONCLUSION: It shows that the muscle power training with
      elastic band can give positive effects in elderly women with hyperglycemia.

PMID- 25960952
TI  - Effects of potato and lotus leaf extract intake on body composition and blood
      lipid concentration.
AB  - PURPOSE: The purpose of this study was to investigate the effects of potato and
      lotus leaf extract intake on body composition, abdominal fat, and blood lipid
      concentration in female university students. METHODS: A total of 19 female
      university students participated in this 8-week study, and they were randomly
      assigned into 2 groups; potato and lotus leaf extract (skinny-line) administered
      group (SKG, n =9) and placebo group (PG, n = 10). The main results of the present
      study are presented below. RESULTS: 1) Body mass index, and percent body fat and
      abdominal fat in students of the SKG showed a decreasing tendency without
      significant interaction, 2) total cholesterol (TC), triglyceride (TG), and low
      density lipoprotein (LDL-C) in students of the SKG showed an averagely decreasing
      tendency and there was a significant interaction of TC only, 3) high density
      lipoprotein (HDL-C) in students of the SKG showed an increasing tendency without
      significant interaction, and 4) Z-score of fatness testing interaction in group *
      repetition did not show a significant interaction; however, there was a
      significant interaction of TC in group * repetition. Based on these results, 8
      week intake of potato and lotus leaf extract had a positive effect of lowering
      TC. On the other hand, it had no significant effect on other types of lipids and
      percent body fat changes. CONCLUSION: There was a positive tendency of blood
      lipids in students of the SKG and it seems that potato and lotus leaf extract
      intake might prevent obesity and improve obesity related syndromes.

PMID- 25960954
TI  - The European thyroid journal reaches adulthood: starting its fourth year of
      publication.

PMID- 25960953
TI  - Effects of different doses of leucine ingestion following eight weeks of
      resistance exercise on protein synthesis and hypertrophy of skeletal muscle in
      rats.
AB  - PURPOSE: This study was designed to determine the appropriate Leucine intake
      volume to obtain the effects of restoring damaged muscle through the synthesis of
      muscle proteins to increase skeletal muscle and improve exercise performance, and
      to achieve enhanced muscle hypertrophy. METHODS: To clarify the effects of
      leucine on skeletal muscle hypertrophy of SD rats, following eight weeks of
      resistance exercise (climbing ladder), the mass of the FHL (Flexor hallucis
      longus) was measured after extraction, after which change in the activity of
      muscle signaling proteins (PKB/Akt, mTOR, p70S6K, 4EBP1) was analyzed. RESULTS:
      The expressions of PKB/Akt, mTOR and p70S6K were increased in L5 (Leucine 50%
      administration group) compared with the control group (CON) and exercise group
      (Ex, exercise training group); EL1 (exercise + 10% leucine administration group)
      and EL5 (exercise + 50% Leucine administration) also exhibited increased
      expressions of PKB/Akt, mTOR, and p70S6K, while no difference between EL1 and EL5
      were observed. No significant differences in 4EBP1 were found among any of the
      groups. In addition, there were no differences in FHL mass, while relative mass
      (FHL/body mass) was increased in the exercise group (Ex, EL1, EL5) compared with
      the control group. No differences were observed among the exercise groups.
      CONCLUSION: The present study demonstrated that the relative body mass was
      increased in the EX group compared with the CON group, while no significant
      differences in muscle mass could be found among the groups. Even though some
      signaling proteins were increased, or some differences existed among groups,
      there were no differences in muscle mass between the leucine administration and
      exercise training combined with leucine administration groups in the present
      study.

PMID- 25960955
TI  - Bioassays for TSH Receptor Antibodies: Quo Vadis?

PMID- 25960956
TI  - DuOx2 Promoter Regulation by Hormones, Transcriptional Factors and the
      Coactivator TAZ.
AB  - The production of H2O2, which is essential to thyroid hormone synthesis, involves
      two NADPH oxidases: dual oxidases 1 and 2 (DuOx1 and DuOx2). A functional study
      with human DuOx genes and their 5'-flanking regions showed that DuOx1 and -2
      promoters are different from thyroid-specific gene promoters. Furthermore, their
      transcriptional activities are not restricted to thyroid cells. While regulation
      of Tg (thyroglobulin) and TPO (thyroperoxidase) expression have been extensively
      studied, DuOx2 promoter regulation by hormones and transcriptional factors need
      to be more explored. Herein we investigated the role of TSH, insulin and insulin
      like growth factor 1 (IGF-1), as well as the cAMP effect on DuOx2 promoter
      (ptx41) activity in transfected rat thyroid cell lines (PCCL3). We also assessed
      DuOx2 promoter activity in the presence of transcriptional factors crucial to
      thyroid development such as TTF-1 (thyroid transcription factor 1), PAX8, CREB,
      DREAM, Nkx2.5 and the coactivator TAZ in HeLa and HEK 293T-transfected cells. Our
      results show that TSH and forskolin, which increase cAMP in thyroid cells,
      stimulated DuOx2 promoter activity. IGF-1 led to pronounced stimulation, while
      insulin induction was not statistically different from DuOx2 promoter basal
      activity. All transcriptional factors selected for this work and coactivator TAZ,
      except DREAM, stimulated DuOx2 promoter activity. Moreover, Nkx2.5 and TAZ
      synergistically increased DuOx2 promoter activity. In conclusion, we show that
      DuOx2 expression is regulated by hormones and transcription factors involved in
      thyroid organogenesis and carcinogenesis, reinforcing the importance of the
      control of H2O2 generation in the thyroid. 

PMID- 25960957
TI  - Rapid bioassay for detection of thyroid-stimulating antibodies using cyclic
      adenosine monophosphate-gated calcium channel and aequorin.
AB  - BACKGROUND: Thyroid-stimulating antibodies (TSAb) are known to be responsible for
      hyperthyroidism in Graves' disease (GD). The conventional methods to measure TSAb
      depend on cell-based assays that require cumbersome procedures and a sterilized
      tissue culture technique. The aim of the present study was to develop a ready-to
      use cell-based assay for measuring TSAb activity without requiring sterilized
      conditions. METHODS: We developed a new assay kit using a frozen Chinese hamster
      ovary cell line expressing the thyroid-stimulating hormone receptor, cyclic
      adenosine monophosphate (cAMP)-gated calcium channel and aequorin, tentatively
      named the aequorin TSAb assay. Activated stimulatory G-protein-coupled adenylate
      cyclase increases intracellular cAMP, which then binds to the cyclic nucleotide
      gated calcium channel. Activation of this channel allows Ca(2+) to enter the
      cell, and the influx of Ca(2+) can be measured with aequorin, which is quantified
      by a luminometer. Results can be obtained in only 4 h without sterilized
      conditions. TSAb activities were expressed by international units using the NIBSC
      08/204 standard. RESULTS: Positive results of aequorin TSAb were obtained in 197
      of 199 (98.9%) of untreated patients with GD. Only 1 of 42 (2.3%) patients with
      painless thyroiditis had a weakly positive aequorin TSAb. All 45 patients with
      subacute thyroiditis and 185 normal subjects showed negative aequorin TSAb. As
      for chronic thyroiditis, all 52 euthyroid patients showed negative aequorin TSAb,
      but 8 of 50 (16.0%) hypothyroid patients had a positive reaction. However, these
      positive reactions were not induced by serum thyroid-stimulating hormone (TSH)
      and were thought to be induced by the stimulating activity of anti-TSH receptor
      immunoglobulins. Conventional porcine TSAb and Elecsys thyroid-stimulating
      hormone receptor antibodies were positive in 69.3 and 95.5% of GD, respectively.
      CONCLUSION: The aequorin TSAb assay was positive in 98.9% of GD and was more
      sensitive than the conventional assay. This assay can be conducted in only 4 h
      without sterilized conditions and is practically useful in general clinical
      laboratories.

PMID- 25960958
TI  - Systemic oxidative stress to nucleic acids is unaltered following radioiodine
      therapy of patients with benign nodular goiter.
AB  - BACKGROUND: Little is known about the whole body oxidative stress burden
      following radioactive iodine ((131)I) therapy of thyroid diseases. METHODS: We
      studied 17 patients with benign nodular goiter treated with (131)I therapy. The
      targeted thyroid dose was 50 Gy in 11 patients pretreated with 0.1 mg of
      recombinant human TSH (rhTSH). In 6 patients, the applied thyroid dose was 100 Gy
      without rhTSH prestimulation. Well-established biomarkers of oxidative stress to
      RNA (8-oxo-7,8-dihydroguanosine; 8-oxoGuo) and DNA (8-oxo-7,8-dihydro-2'
      deoxyguanosine; 8-oxodG) were measured in freshly voided morning urine
      (normalized against the creatinine concentration) at baseline, and 7 and 21 days
      after rhTSH (not followed by (131)I), and 7 and 21 days after (131)I therapy,
      respectively. RESULTS: The baseline urinary excretions of 8-oxoGuo and 8-oxodG
      were 2.20 +/- 0.84 and 1.63 +/- 0.70 nmol/mmol creatinine, respectively. We found
      no significant changes in the excretion of any of the metabolites, neither after
      rhTSH stimulation alone nor after (131)I therapy. Also, no significant
      differences were found between the rhTSH group (low dose, median (131)I: 152 MBq)
      and the non-rhTSH group (high dose, median (131)I: 419 MBq; 8-oxoGuo: p = 0.66, 8
      oxodG: p = 0.71). CONCLUSION: Systemic oxidative stress, as detected by nucleic
      acids metabolites in the urine, is not increased after thyroid stimulation with
      0.1 mg of rhTSH, or after (131)I therapy. Our method cannot quantify the
      oxidative stress induced locally in the thyroid gland, but the study supports
      that (131)I therapy of benign nodular goiter carries no or only a minute risk of
      developing subsequent malignancies. It remains to be explored whether our
      findings also apply to hyperthyroid disorders.

PMID- 25960959
TI  - Iodine, thyroid autoimmunity and cancer.
AB  - This review focuses on two different topics: (a) iodine and autoimmune thyroid
      disease (AITD) and (b) AITD and papillary thyroid carcinoma (PTC). Iodine intake
      modifies the expression of thyroid diseases and has been associated with
      induction of AITD. Thyroglobulin (Tg) is an important target in iodine-induced
      autoimmune response due to post-translational modifications of iodinated Tg, as
      suggested in animal models. We have shown that the unmasking of a cryptic epitope
      on Tg contributes to iodine-induced thyroid autoimmunity in humans. The
      relationship between AITD and PTC has been suggested in many studies. The
      presence of two different mechanisms has been hypothesized, one typical of AITD
      and the other of an immune reaction to PTC. We have shown that in AITD, the
      pattern of Tg recognition by anti-Tg antibodies (TgAb) is 'restricted' to the
      immunodominant regions of Tg, while in patients with non-AITD, such as nodular
      goiter and PTC devoid of thyroid lymphocytic infiltration at histology, TgAb show
      a less restricted epitopic pattern and bind also to other regions of Tg. Thyroid
      function may also affect the frequency of PTC, the risk of cancer increasing with
      serum TSH levels. We have shown that this mechanism, rather than thyroiditis per
      se, plays a major role in the association of PTC with Hashimoto's thyroiditis, as
      a consequence of the autoimmune process leading to a progressive increase of
      serum TSH in these patients. 

PMID- 25960960
TI  - Excessive iodine intake does not increase the recurrence rate of graves' disease
      after withdrawal of the antithyroid drug in an iodine-replete area.
AB  - BACKGROUND AND OBJECTIVES: The relationship between iodine intake and effects of
      antithyroid drugs (ATD) for Graves' disease, especially in iodine-deficient
      areas, has been demonstrated in many studies. However, it was not clear how
      chronic high iodine intake influenced the effectiveness of ATD in an iodine
      replete area. This study aimed to clarify the effect of iodine intake on clinical
      outcomes of Graves' disease after discontinuation of ATD in Korea, an iodine
      replete area. METHODS: A total of 142 patients with Graves' disease who visited
      the outpatient clinic regularly and stopped their ATD between October 2011 and
      April 2013 were enrolled in our study. Urinary iodine concentration (UIC) was
      measured just before and after the discontinuation of ATD. RESULTS: Median UIC
      was not significantly different between the remission and relapse groups, as well
      as among the four treatment groups (group 1, remission after initial treatment;
      group 2, remission after repeated treatment; group 3, early relapse within a
      year; group 4, late relapse after a year). Remission rates did not show a
      significant difference between the excessive iodine intake (UIC >=300 MUg/l) and
      average iodine intake groups (UIC <300 MUg/l). CONCLUSIONS: The present study
      suggests that excessive iodine intake does not have an effect on the clinical
      outcomes of Graves' disease in an iodine-replete area, and therefore diet control
      with iodine restriction might not be necessary in the management of Graves'
      disease.

PMID- 25960961
TI  - The effect of hypothyroidism on color contrast sensitivity: a prospective study.
AB  - BACKGROUND: Thyroid hormone has been shown to control retinal cone opsin
      expression, the protein of color vision, in adult rodents. OBJECTIVES: The aim of
      this study was to evaluate the effect of hypothyroidism on color contrast
      sensitivity in adult overt hypothyroid patients. METHODS: Thirty-eight overt
      hypothyroid (31 females, 7 males) subjects and 20 euthyroid (16 females, 4 males)
      controls were studied prospectively. Color vision examination was performed by
      Chromatest, a software program analyzing the tritan (blue-yellow) color contrast
      threshold (tritan CCT) and protan (red-green) color contrast threshold (protan
      CCT). Color contrast sensitivity analyses of hypothyroid subjects were performed
      on admission and after L-thyroxine treatment when biochemical euthyroidism was
      achieved. RESULTS: After a median period of 90 (90-210) days, 24 (19 females, 5
      males) patients were euthyroid and eligible for a second color vision
      examination. Baseline tritan CCT and protan CCT values were significantly higher
      in the hypothyroid group compared to euthyroid controls, which clinically
      translates into impaired color contrast sensitivity (p < 0.001 and p < 0.001,
      respectively). There was a significant decrease in tritan CCT (p = 0.002) and
      protan CCT (p < 0.001) values in the hypothyroid group after euthyroidism was
      achieved, which denotes improvement in color contrast sensitivity. CONCLUSIONS:
      It is a novel finding of the current study that color contrast sensitivity is
      impaired in hypothyroidism and significantly improves after euthyroidism is
      achieved.

PMID- 25960962
TI  - Differences in physicians' and patients' perception of acute hypothyroid symptoms
      induced by thyroid hormone withdrawal in thyroid cancer patients: a multicenter
      survey in Korea.
AB  - BACKGROUND: Acute short-term hypothyroidism induced by thyroid hormone withdrawal
      (THW) for follow-up surveillance or therapeutic radioiodine causes patients with
      differentiated thyroid cancer to suffer from a myriad of deleterious symptoms.
      OBJECTIVES: To know how patient recognition of hypothyroid symptoms compares to
      physician perception of patient symptoms. METHODS: The survey was performed in 10
      referral hospitals throughout Korea from December 2010 to May 2011 and targeted
      patients with total thyroidectomy and remnant ablation. The survey consisted of
      questions regarding the effect of THW on patient symptoms, the duration of
      symptoms, impact on social life, and patient complaints. The physicians treating
      thyroid cancer patients also responded to the survey and provided their
      perceptions of patient symptoms and treatment decisions. RESULTS: About 70% of
      the patients responded that they experienced a negative physical or psychological
      impact on their life and work due to hypothyroid symptoms. However, 76% of
      doctors thought hypothyroidism could negatively impact a patient's daily life but
      would be endurable. Two thirds of physicians do not routinely recommend
      recombinant human TSH (rhTSH) to their patients. Multivariate analysis showed
      patients with female sex, stronger educational background, emotionally negative
      experiences of hypothyroidism, and younger age were more willing to pay for
      therapy that could prevent hypothyroidism symptoms. CONCLUSIONS: There was a
      substantial gap in the perception of hypothyroid symptoms during THW between
      physicians and patients. Physicians who are aware of the seriousness of
      hypothyroidism in their patients were more likely to recommend the use of rhTSH
      for their patients.

PMID- 25960964
TI  - Rhabdomyolysis in the setting of induced hypothyroidism and statin therapy: a
      case report.
AB  - Mild elevation of creatine kinase (CK) is common in untreated hypothyroidism, but
      severe myositis and overt rhabdomyolysis are rare. Similarly, muscle pain and CK
      elevation are potential side effects of statin therapy, yet rhabdomyolysis is
      likewise rare in the absence of medication interactions adversely affecting
      statin metabolism. The coexistence of statin therapy and hypothyroid states may
      synergistically increase the risk of myopathy. We describe a case of
      rhabdomyolysis attributable to induced hypothyroidism in a patient on chronic
      statin medication who was anticipating adjuvant radioiodine ((131)I) therapy for
      a thyroid carcinoma. 

PMID- 25960963
TI  - Thyroid volume and its relation to anthropometric measures in a healthy cuban
      population.
AB  - OBJECTIVES: The aim of this study was to describe the thyroid volume in healthy
      adults by ultrasound and to correlate this volume with some anthropometric
      measures and other differentiated thyroid cancer risk factors. STUDY DESIGN:
      Thyroid volume and anthropometric measures were recorded in a sample of 100
      healthy adults, including 21 men and 79 women aged 18-50 years, living in a non
      iodine-deficient area of Havana city. RESULTS: The average thyroid volume was 6.6
      +/- 0.26 ml; it was higher in men (7.3 ml) than in women (6.4 ml; p = 0.15). In
      the univariate analysis, thyroid volume was correlated with all anthropometric
      measures, but in the multivariate analysis, body surface area was found to be the
      only significant anthropometric parameter. Thyroid volume was also higher in
      current or former smokers and in persons with blood group AB or B. CONCLUSION:
      Specific reference values of thyroid volume as a function of body surface area
      could be used for evaluating thyroid volume in clinical practice. The relation
      between body surface area and thyroid volume is coherent with what is known about
      the relation of thyroid volume to thyroid cancer risk, but the same is not true
      about the relation between thyroid volume and smoking habit.

PMID- 25960965
TI  - Concurrent Medullary, Papillary, and Follicular Thyroid Carcinomas and
      Simultaneous Cushing's Syndrome.
AB  - BACKGROUND: Papillary thyroid carcinoma is the most common thyroid cancer (85%).
      Follicular thyroid carcinoma is the second most common type of thyroid cancer,
      accounting for up to 10% of all thyroid cancers. Medullary thyroid carcinoma
      accounts for only 5-8% of thyroid cancers. Concurrent medullary, follicular, and
      papillary carcinomas of the thyroid gland are extremely rare and reported
      scarcely. CASE REPORT: A 72-year-old male presented with nonspecific neck pain.
      The workup revealed a nodular thyroid gland with a follicular lesion on fine
      needle aspiration. Total thyroidectomy was performed and pathological examination
      identified a 25-mm follicular carcinoma, two papillary microcarcinomas, and two
      medullary microcarcinomas. The genetic workup was negative and no other family
      members were diagnosed with any endocrinopathy. Two months after surgery, the
      patient was diagnosed with Cushing's syndrome that was treated with laparoscopic
      left adrenalectomy. On 3-year follow-up, the patient is asymptomatic with no
      evidence of recurrent disease. CONCLUSION: We present a rare case of a patient
      with follicular, papillary, and medullary thyroid carcinoma, and Cushing's
      syndrome. To date, no known genetic mutation or syndrome can account for this
      combination of neoplastic thyroid and adrenal pathologies, although future
      research may prove differently.

PMID- 25960966
TI  - A Fresh Look at the Relationship between TSH and Free Thyroxine in Cross
      Sectional Data.

PMID- 25960967
TI  - Iodine status of schoolchildren in hungary: improvement a decade on.

PMID- 25960968
TI  - Adenoma detection rate in patients younger than 50 years of age: relationship of
      the adenoma detection rate to interval cancer.

PMID- 25960969
TI  - The wind of change: uncomplicated diverticulitis.

PMID- 25960970
TI  - Different strategies for treating a colovesical fistula.

PMID- 25960971
TI  - Distribution of the colonoscopic adenoma detection rate according to age: is
      recommending colonoscopy screening for koreans over the age of 50 safe?
AB  - PURPOSE: This study was conducted to determine the distributions of the polyp
      detection rate (PDR) and the adenoma detection rate (ADR) according to age by
      analyzing the polypectomy results. METHODS: A total of 10,098 patients who
      underwent a colonoscopy in 2013 were included in this study. Chi-square and
      logistic regression statistical analyses were performed using SPSS ver. 19.
      RESULTS: The mean age of the patients was 52.7 years old (median, 54 +/- 12.52
      years; range, 14 to 92 years). A total of 6,459 adenomatous polyps (61.7%) from a
      total of 10,462 polyps were eliminated. The PDR was 50.9% (5,136/10,098), and
      the. ADR was 35.4% (3,579/10,098). The male-to-female ratio was 51.3%:48.7%, with
      a male-to-female ADR ratio of 42.8% : 27.7% (P < 0.001). In the age distribution,
      the values of the ADR were 0% for patients in their 10's, 6.3% for those in their
      20's, 14.0% for those in their 30's, 28.7% for those in their 40's, 38.4% for
      those in their 50's, 46.2% for those in their 60's, 55.8% for those in their
      70's, 56.1% for those in their 80's, and 33.3% for those in their 90's. In males,
      the values of the ADR were 0%, 9.1%, 17.1%, 37.8%, 48.2%, 53.6%, 61.7%, 59.1%,
      and 33.3% for the same age distribution, and a steep increase was found between
      patients in their 30's and patients in their 40's. Significant (P < 0.001)
      factors influencing the ADR included sex, previous colonoscopy experience,
      polypectomy method, and age of more than 40 years. CONCLUSION: In considering the
      adenoma carcinoma sequence, 28.7% of people, especially 37.8% of males in their
      40's showed adenomatous polyps. Whether an earlier first-time colonoscopy will
      have better results in preventing colorectal cancer should be investigated and
      discussed.

PMID- 25960972
TI  - Short-term Intravenous Antibiotic Treatment in Uncomplicated Diverticulitis Does
      Not Increase the Risk of Recurrence Compared to Long-term Treatment.
AB  - PURPOSE: This study included all patients treated at the University Hospital of
      Geneva for a first episode of uncomplicated diverticulitis. Risks of recurrence
      and treatment failure were evaluated by comparing the results between short
      course and long-course intravenous (IV) antibiotic therapy groups. METHODS: The
      records of all patients hospitalized at our facility from January 2007 to
      February 2012 for a first episode of uncomplicated diverticulitis (Hinchey Ia),
      as confirmed by computed tomography, were prospectively collected. We published
      an auxiliary analysis from this registered study at Clinicaltrials.gov
      (identifier number: NCT01015378). Two groups of patients were considered: one
      received a short-course IV antibiotic arm (ceftriaxone and metronidazole) for up
      to 5 days (followed by 5 days of oral antibiotics); the other received a long
      course IV arm between days 5 and 10. The primary outcome was the recurrence-free
      survival time. RESULTS: Follow-up was completed for 256 patients-50% men and 50%
      women, with a median age of 56 years (range, 24-85 years). The average follow-up
      was 50 months (range, 19-89 months). Of the 256 patients included in the study,
      46 patients received a short-course IV antibiotic treatment and 210 received a
      long-course treatment. The recurrence-free survivals were very similar between
      the two groups, which was supported by a log rank test (P = 0.772). Four
      treatment failures, all in the long-course IV antibiotic treatment group,
      occurred. CONCLUSION: Treatment of diverticulitis with a short IV antibiotic
      treatment is possible and does not modify the recurrence rate in patients with
      uncomplicated diverticulitis.

PMID- 25960973
TI  - Colovesical fistula: should it be considered a single disease?
AB  - PURPOSE: This research was conducted to compare the management and the outcome of
      patients with colovesical fistulae of different aetiologies. METHODS:
      Retrospective data were collected from 2002 to 2012 and analyzed with SPSS ver.
      17. Age, gender, aetiology, management, hospital stay, postoperative
      complications, and mortality were studied and compared among colovesical fistulae
      of different aetiologies. RESULTS: A total of 55 patients, 46 males (84%) and 9
      females (16%), with a median age of 65 years (interquartile range [IQR], 48-75
      years) were studied. Diverticular disease was the most common benign cause and
      recto-sigmoid cancer the most common malignancy. Anterior resection and bladder
      repair were the most frequent operations in benign cases, as was total pelvic
      exenteration in the malignant group. Multiple intestinal loop involvement and
      subsequent resection were significantly higher in those with Crohn disease than
      it was in patients of colovesical fistula due to all other causes collectively
      (60% vs. 6%, P = 0.006). Patients with malignancy had a higher postoperative
      complication rate than patients who did not (12 [80%] vs. 7 [32%], P = 0.0005).
      Pelvic collection (11, 22%) was the most frequent early complication
      (predominantly in the malignant group) whereas incisional hernia (8, 22%) was the
      most common late complication, with a predominance in the benign group. The
      median hospital stay was significantly prolonged in the malignant group (32 days;
      IQR, 17-70 days vs. 16 days; IQR, 11-25 days; P < 0.001). CONCLUSION: Despite
      their having similar clinical presentation, colovesical fistulae of various
      aetiologies differ significantly in management and outcome.

PMID- 25960974
TI  - Insertion of totally implantable central venous access devices by surgeons.
AB  - PURPOSE: The aim of this study is to evaluate the results for the insertion of
      totally implantable central venous access devices (TICVADs) by surgeons. METHODS:
      Total 397 patients, in whom TICVADs had been inserted for intravenous
      chemotherapy between September 2008 and June 2014, were pooled. This procedure
      was performed under local anesthesia in an operation room. The insertion site for
      the TICVAD was mainly in the right-side subclavian vein. In the case of breast
      cancer patients, the subclavian vein opposite the surgical site was used for
      insertion. RESULTS: The 397 patients included 73 males and 324 females. Primary
      malignant tumors were mainly colorectal and breast cancer. The mean operation
      time was 54 minutes (18-276 minutes). Operation-related complications occurred in
      33 cases (8.3%). Early complications developed in 15 cases with catheter
      malposition and puncture failure. Late complications, which developed after 24
      hours, included inflammation in 6 cases, skin necrosis in 6 cases, hematoma in 3
      cases, port malfunction in 1 case, port migration in 1 case, and intractable pain
      at the port site in 1 case. CONCLUSION: Insertion of a TICVAD under local
      anesthesia by a surgeon is a relatively safe procedure. Meticulous undermining of
      the skin and carefully managing the TICVAD could minimize complications.

PMID- 25960975
TI  - Primary extrauterine endometrial stromal sarcoma in the sigmoid colon.
AB  - An endometrial stromal sarcoma (ESS) is an uncommon uterine neoplasm, and its
      primary occurrence in the intestine as an extrauterine ESS (EESS) is exceedingly
      rare. We hereby report a primary EESS arising in the sigmoid colon with a review
      of the literature. A 52-year-old woman presented with bloody stool and underwent
      a colon fiberscopy, which revealed a fungating mass obstructing the lumen at the
      distal sigmoid. A laparoscopic low anterior resection was performed, and an
      umbilicated polypoid mass was identified; on section, it had infiltrated the
      mesocolic fat and measured 3.8 cm * 2.5 cm. The tumor showed geographic sheets or
      nests composed of relatively monotonous stromal cells, expansion or infiltration
      to the proper muscle and mesocolic fat, and extensive lymphovascular invasion and
      metastasis to regional lymph nodes and the pelvic peritoneum. The tumor cells
      were strongly and diffusely immunoreactive for CD10, but negative for c-kit,
      CD34, and Dog1. Two months later, a hysterectomy with a bilateral salpingo
      oophorectomy was performed, and no evidence of an ESS was found in the uterus. 

PMID- 25960976
TI  - Peritoneal metastatic goblet-cell carcinoid tumor treated with cytoreductive
      surgery and intraperitoneal chemotherapy.
AB  - We report a case of a goblet-cell carcinoid tumor of the appendix which
      metastasized to the peritoneum and was treated by using cytoreductive surgery
      (CRS) with intraperitoneal chemotherapy. A 47-year-old male presented with
      chronic constipation and was diagnosed as having a rectal adenocarcinoma with a
      signet-ring-cell component under colonoscopy. Computed tomography suggested
      peritoneal metastases with diffuse nodular parietal peritoneal thickening of the
      entire abdomen and focal invasion of the upper rectum by a seeding mass. CRS with
      intraperitoneal chemotherapy was done under the diagnosis of a rectal
      adenocarcinoma with peritoneal metastases. The pathologic diagnosis was a goblet
      cell carcinoid tumor of the appendix with peritoneal metastasis. The histological
      discrepancy between a peritoneal metastatic mass and a rectal mass was due to the
      mixed histological pattern of a goblet-cell carcinoid tumor. A metastatic mass
      may not share identical immunohistochemical characteristics from its origin. This
      histologic discrepancy necessitates caution in diagnosing a distant metastasis of
      a goblet-cell carcinoid tumor. 

PMID- 25960977
TI  - Usefulness of measuring isokinetic torque and balance ability for exercise
      rehabilitation.

PMID- 25960978
TI  - Difference, significant difference and clinically meaningful difference: The
      meaning of change in rehabilitation.
AB  - The valid confirmation of a positive change (improvement) in a patient's health
      status due to intervention has been at the core of medicine and rehabilitation
      since their very inception as clinicians always aspired to ensure that treating
      their patients had led to successful outcomes both in acute and chronic
      conditions. However what is change: either improvement or worsening
      (aggravation), is a complicated issue which involves clinical as well as
      statistical considerations. Change invariably relates to a difference in some
      measurable entity and almost always it relates to a time span. The confirmation
      of clinical change is important both for varying the treatment course (if
      necessary) and for the termination of treatment when the latter has reached
      wither its prescribed objective or a plateau. Since in the context of
      rehabilitation, the outcome measures (OM) are strongly linked to performance,
      determination of change in the latter is confounded by many factors, collectively
      known as the error of measurement, which render a decision regarding clinically
      meaningful change, highly involved. This is further complicated by the stability
      of the observed OM, the so-called reproducibility of the OM, and the accuracy of
      the measurement instrument. The higher the reproducibility the lower is the
      error. Moreover, in order to proclaim change, in most cases a positive one, it is
      necessary for the difference in outcome scores (i.e. the change) to surpass the
      error of measurement, in varying degree of rigor. This paper describes selected
      methods associated with determination of change and focuses predominantly on the
      difference between a simple difference in scores ('simple change'), a significant
      difference in scores and the so-called clinically meaningful change in scores
      which is considered today as the benchmark for confirmation of a real change. 

PMID- 25960979
TI  - Pulmonary rehabilitation and exercise in pulmonary arterial hypertension: An
      underutilized intervention.
AB  - Pulmonary arterial hypertension (PAH) is a rare and devastating disease
      characterized by progressive increases in pulmonary arterial pressure and
      pulmonary vascular resistance which eventually leads to right ventricular failure
      and death. Early thought process was that exercise and increased physical
      activity may be detrimental to PAH patients however many small cohort trials have
      proven otherwise. In addition to the many pharmaceutical options, exercise and
      pulmonary rehabilitation have also been shown to increase exercise capacity as
      well as various aspects of psychosomatic health. As pulmonary and exercise
      rehabilitation become more widely used as an adjuvant therapy patient outcomes
      improve and physicians should consider this in the therapeutic algorithm along
      with pharmacotherapy. 

PMID- 25960980
TI  - Treadmill exercise prevents GABAergic neuronal loss with suppression of neuronal
      activation in the pilocarpine-induced epileptic rats.
AB  - Epilepsy is a common neurological disorder characterized by seizure and loss of
      neuronal cells by abnormal rhythmic firing of neurons in the brain. In the
      present study, we investigated the effect of treadmill exercise on gamma
      aminobutyric acid (GABA)ergic neuronal loss in relation with neuronal activation
      using pilocarpine-induced epileptic rats. The rats were divided into four groups:
      control group, control and treadmill exercise group, pilocarpine-induced epilepsy
      group, and pilocarpine-induced epilepsy and treadmill exercise group. Epilepsy
      was induced by intraperitoneal injection of 320 mg/kg pilocarpine hydrochloride.
      The rats in the exercise groups were forced to run on a motorized treadmill for
      30 min once a day for 2 weeks. In the present results, neuronal loss in the
      hippocampal CA1 region was increased after pilocarpine-induced seizure. Treadmill
      exercise inhibited hippocampal neuronal loss in the epileptic rats. Glutamic acid
      decarboxylase (GAD67) expression in the hippocampal CA1 region was reduced by
      pilocarpine-induced seizure. Treadmill exercise increased GAD67 expression in the
      epileptic rats. c-Fos expression in the hippocampal CA1 region was increased in
      response to epileptic seizure. Treadmill exercise inhibited c-Fos expression in
      the epileptic rats. Epileptic seizure increased brain-derived neurotrophic factor
      (BDNF) and tyrosine kinase receptor B (TrkB) expressions in the hippocampus.
      Treadmill exercise suppressed BDNF and TrkB expressions in the epileptic rats. In
      the present study, treadmill exercise prevented GABAergic neuronal loss and
      inhibited neuronal activation in the hippocampal CA1 region through the down
      regulation of BDNF-TrkB signaling pathway. 

PMID- 25960981
TI  - Treadmill exercise decreases incidence of Alzheimer's disease by suppressing
      glycogen synthase kinase-3beta expression in streptozotocin-induced diabetic
      rats.
AB  - Diabetes is a metabolic disorder, and it is considered as a major risk factor for
      Alzheimer's disease (AD). In the present study, we evaluated whether treadmill
      exercise ameliorates progression of AD in relation with glycogen synthase kinase
      3beta (GSK-3beta) activity using streptozotocin (STZ)-induced diabetic rats. For
      this study, step-down avoidance task, immunohistochemistry for glycogen synthase
      kinase-3beta (GSK-3beta) and tau, and western blot for phosphor-phosphoinositide
      3 kinase (p-PI3K)/PI3K and phosphor-Akt (p-Akt)/Akt were performed. Diabetes
      mellitus was induced by intraperitoneal injection of STZ. The rats in the
      exercise groups were made to run on the treadmill for 30 min per one day, five
      times a week, during 12 weeks. The present results showed that short-term and
      long-term latencies in the step-down avoidance task were decreased by induction
      of diabetes, and treadmill exercise inhibited these latencies in the diabetic
      rats. Induction of diabetes suppressed the ratio of p-PI3K to PI3K and the ratio
      of p-Akt to Akt, and treadmill exercise increased these ratios in the diabetic
      rats. The numbers of GSK-3beta-positive and tau-positive cells in the hippocampal
      dentate gyrus was higher in the diabetes-induction group than that in the control
      group, and treadmill exercise inhibited these numbers in the diabetic rats. In
      the present study, treadmill exercise suppressed hyperphosphorylation of tau in
      the hippocampus by decreased GSK-3beta activity through PI3K/Akt pathway
      activation in the diabetic rats. Based on the present results, treadmill exercise
      may helpful to prevent diabetes-associated AD occurrence. 

PMID- 25960982
TI  - Isokinetic dynamometer evaluation of the effects of early thigh diameter
      difference on thigh muscle strength in patients undergoing anterior cruciate
      ligament reconstruction with hamstring tendon graft.
AB  - After anterior cruciate ligament (ACL) reconstruction, which muscle groups are
      more affected from frequently developing thigh muscle atrophy is a matter of
      debate. We evaluate the effect of thigh circumference difference between
      patients' knees who were administered the ACL reconstruction with hamstring
      tendon autograft and intact knees, on torque between the hamstring and quadriceps
      muscles. Fifty-five patients at least 6 months follow-up period available were
      included in our study. Power measurements of quadriceps and hamstring muscle
      groups in patients' extremities were done by using isokinetic dynamometer. The
      maximum torque values at 60 degrees /sec, 240 degrees /sec in frequency,
      positions of flexion and extension were determined. In accordance with our
      findings it is still possible to encounter the thigh atrophy in average 28 months
      after ACL reconstruction surgery even under physical rehabilitation programs and
      appropriate follow-up. It is inevitable for the clinician to consider these
      changes in diagnosis and rehabilitation stages. It can't be ignored that muscle
      weakness mechanisms developing in the thigh circumference vary according to the
      thigh muscle group and knee flexors play an important role in thigh atrophy when
      determining an appropriate rehabilitation program after reconstruction
      application. 

PMID- 25960983
TI  - Effect of 8 weeks of pre-season training on body composition, physical fitness,
      anaerobic capacity, and isokinetic muscle strength in male and female collegiate
      taekwondo athletes.
AB  - The purpose of the study was to determine the effect of 8 weeks pre-season
      training on body composition, physical fitness, anaerobic capacity, and
      isokinetic strength in collegiate taekwondo athletes. Thirty-four collegiate
      athletes (male: 22, female: 12) participated. Body composition, bone mineral
      density, physical fitness, anaerobic capacity, and isokinetic muscle strength
      were tested. After statistical analysis was performed the results indicated that
      there were significant decreases in body weight, percent body fat, and fat tissue
      after 8 weeks of pre-season training. Bone mineral density increased
      significantly only in males. There were significant improvements in the 50 m
      shuttle run and 20 m multistage endurance run in both males and females. The sit
      & reach test and standing long jump were not significantly changed after 8 weeks.
      Relative peak power and anaerobic capacity were significantly improved in males.
      Significant increases in angular velocity were observed for knee extension at
      both % BW 60 degrees /sec and 180 degrees /sec in both males and females. A
      significant increase in angular velocity was seen for right knee flexion at % BW
      60 degrees /sec for males, but it decreased at % BW 180 degrees /sec for both
      males and females. In conclusion, this study suggests that 8 weeks of pre-season
      training has a positive effect on body composition, physical fitness, anaerobic
      capacity, isokinetic muscular strength, and endurance. Nevertheless, an exercise
      approach with the goal of increasing lean tissue, and improving power in knee
      flexors and flexibility of athletes, should be included in the training program. 

PMID- 25960984
TI  - Relation of the factor to menstrual pain and musculoskeletal pain.
AB  - The purpose of the present study is to investigate the relationship between the
      regions of menstrual pain and of myofascial pain syndrome, which is the main
      cause of musculoskeletal pain, as well as to examine the changes and
      relationships among the menstrual pain-related factors, which are pain level,
      pain area, activity, appetite, mood, and sleeping pattern. The subjects were 13
      sufferers of musculoskeletal pain and 17 non-sufferers. Pain diary and pain chart
      systems were used for the measurement of menstrual pain-related factors and
      musculoskeletal pain. Data were analyzed using repeated ANOVA. The results show
      that there are significant differences between the two groups in pain level,
      activity, and mood during menstruation periods (P< 0.05). The area of
      musculoskeletal pain and menstrual pain were found to be the same. 

PMID- 25960985
TI  - Development of a non-damaging high-intensity intermittent running protocol.
AB  - The aim of the present study was to devise a non-damaging high-intensity
      intermittent running protocol. Ten healthy active men completed high-intensity
      interval running (8* 3-min bouts at 90% of maximal oxygen uptake interspersed
      with 3-min recovery) on a motorized treadmill under normal laboratory
      temperatures. Mean heart rate and rating of perceived exertion significantly
      increased during the intermittent protocol (the first bout, 15.3+/- 1.2; the
      final bout, 18.6+/- 0.9; P< 0.001). Blood lactate concentrations were
      significantly elevated following bout 1 compared with resting values (1.2+/- 0.3
      mmol/L vs 5.4+/- 2.4 mmol/L; P = 0.03). However, no significant reduction in
      maximal voluntary contraction was observed immediately after completing the last
      exercise bout (623.9+/- 143.6 N) or during the subsequent 7-d period compared to
      pre-exercise values (P = 0.59). Creatine kinase (CK) concentrations were not
      significantly increased following exercise or during the subsequent 7-d period (P
      = 0.96). Myoglobin (Mb) content was significantly increased following exercise (P
      = 0.01), however, values returned towards pre-exercise concentrations after 24 h.
      These results indicate that the high-intensity intermittent running protocol
      induced changes in physiological and subjective indices that are consistent with
      the effects of acute fatigue as opposed to those changes normally associated with
      exercise-induced muscle damage. This exercise protocol can therefore be used to
      investigate the influence of high-intensity exercise from physiological responses
      to molecular adaptation. 

PMID- 25960986
TI  - Protective effect of ischemic postconditioning against hepatic ischemic
      reperfusion injury in rat liver.
AB  - PURPOSE: The efficiency of ischemic postconditioning (IPC) was evaluated in a rat
      model of ischemic liver. Concentration of survivin of liver tissue correlated
      with the degree of antiapoptosis, so survivin was estimated to evaluate the
      efficiency of IPC on ischemic reperfusion (IR) injury. METHODS: Twenty-four
      healthy rats were divided to three groups (SHAM, IR, and IPC). Rats in the SHAM
      group displayed no change during 3 hours. Rats in the IR group were ischemic
      within 1 hour of clamping the left hepatic artery and left portal vein.
      Reperfusion for 2 hours was then done. IPC group, intermittent 2, 3, 5, and 7
      minutes of reperfusion followed by 1 hour of warm ischemia. Two-minute
      reocclusion was done after each reperfusion. Rat sera were analyzed for AST and
      ALT, and Western blot analysis of rat liver tissue of rats evaluated
      malondialdehyde (MDA) and survivin. RESULTS: MDA in the liver tissue of rats in
      the IR and IPC group were significantly high than in the liver tissue of the SHAM
      group (P = 0.003 and P = 0.008, respectively). Survivin was higher in the IPC
      group than in the SHAM and IR groups (P = 0.021 and P = 0.024, respectively).
      CONCLUSION: IPC could not prevent lipid oxidation in liver cell mitochondria, but
      did aid in the regeneration of ischemic injured liver cells. The results indicate
      that IPC can suppress the apoptosis of liver cells and reduce reperfusion injury
      of liver tissue.

PMID- 25960987
TI  - Laparoscopic sleeve gastrectomy in obese Korean patients: up to 4-year follow-up
      in a single center.
AB  - PURPOSE: Laparoscopic sleeve gastrectomy (LSG) has been gaining marked popularity
      as a stand-alone treatment for morbid obesity. This study aimed to evaluate the
      midterm outcomes and efficacy of LSG performed at a single center in Korea.
      METHODS: The records of 192 consecutive patients who underwent LSG between April
      2009 and December 2012 were retrospectively reviewed. The patients' demographics
      and surgical outcomes including anthropometric data were analyzed. RESULTS: The
      mean preoperative body mass index was 40.0 +/- 7.2 kg/m(2), and 120 patients
      (62.5%) had at least one obesity-related comorbidity. Three patients (1.6%)
      required endoscopic or surgical intervention to manage postoperative bleeding or
      leakage. At the postoperative 1-, 2-, 3-, and 4-year follow-ups, the mean percent
      of excess weight loss (%EWL) values were 72.6%, 80.6%, 71.1%, and 57.8%,
      respectively, with follow-up rates of 81%, 56%, 58%, and 30% respectively. The
      overall mean %EWL reached 68.3% +/- 27.2% at a mean follow-up of 25 months.
      Obesity-related comorbidities were resolved in >70% of the patients after
      surgery. Twelve months after LSG, 25 patients (13.0%) showed a %EWL of <50%; 9
      (4.7%) required conversion to gastric bypass due to inadequate weight loss,
      intolerable reflux symptoms, or intractable diabetes. CONCLUSION: These midterm
      results show that LSG is a safe and effective surgical procedure for morbidly
      obese patients. However, a longer follow-up period is necessary to elucidate
      whether LSG can achieve durable weight loss and long-term outcomes, comparable to
      those of more aggressive procedures.

PMID- 25960988
TI  - Oncologic outcomes following metastasectomy in colorectal cancer patients
      developing distant metastases after initial treatment.
AB  - PURPOSE: We performed a comparative analysis of the clinicopathologic features
      and oncologic outcomes of colorectal cancer patients with metachronous versus
      synchronous metastasis, according to the prognostic factors. METHODS: Ninety
      three patients who underwent curative resection for distant metastatic colorectal
      cancer were included in the study between December 2001 and December 2011. We
      assessed recurrence-free survival and overall survival in patients with distant
      metastasis who underwent curative surgery. RESULTS: The most common site of
      distant metastasis was lung alone (n = 19, 51.4%) in patients with metachronous
      metastasis, while liver alone was most common in those with synchronous
      metastasis (n = 40, 71.4%). Overall survival rate was significantly different
      between patients with synchronous metastasis and metachronous metastasis (34.0%
      vs. 53.7%; P = 0.013). Incomplete resection of the metastatic lesion was
      significantly related to poor overall survival in both, patients with synchronous
      metastasis, and metachronous metastasis. CONCLUSION: Our study indicates that
      patients developing distant metastasis after initial treatment show a different
      metastatic pattern and better oncologic outcomes, as compared to those presenting
      with distant metastasis. Resection with tumor free margins significantly improves
      survival in patients with metachronous as well as synchronous metastasis.

PMID- 25960989
TI  - Comparative study between transanal tube and loop ileostomy in low anterior
      resection for mid rectal cancer: a retrospective single center trial.
AB  - PURPOSE: To investigate the efficacy and safety of the transanal tube (TAT) in
      preventing anastomotic leak (AL) in rectal cancer surgery. METHODS: Clinical data
      of the patients who underwent curative surgery for mid rectal cancer from
      February 2010 to February 2014 were reviewed retrospectively. Rectal cancers
      arising 5 to 10 cm above the anal verge were selected. Patients were divided into
      the ileostomy, TAT, or no-protection groups. Postoperative complications
      including AL and postoperative course were compared. RESULTS: We included 137
      patients: 67, 35, and 35 patients were included in the ileostomy, TAT, and no
      protection groups, respectively. Operation time was longer in the ileostomy group
      (P = 0.029), and more estimated blood loss was observed (P = 0.018). AL occurred
      in 5 patients (7.5%) in the ileostomy group, 1 patients (2.9%) in the TAT group,
      and 6 patients (17.1%) in the no-protection group (P = 0.125). Patients in the
      ileostomy group resumed diet more than 1 day earlier than those in the other
      groups (P = 0.000). Patients in the no-protection group had about 1 or 2 days
      longer postoperative hospital stay (P = 0.048). The ileostomy group showed higher
      late complication rates than the other groups as complications associated with
      the stoma itself or repair operation developed (P = 0.019). CONCLUSION: For mid
      rectal cancer surgery, the TAT supports anastomotic site protection and diverts
      ileostomy-related complications. Further large scale randomized controlled
      studies are needed to gain more evidence and expand the range of TAT usage.

PMID- 25960990
TI  - Learning curves for single incision and conventional laparoscopic right
      hemicolectomy: a multidimensional analysis.
AB  - PURPOSE: This study aimed to compare the learning curves and early postoperative
      outcomes for conventional laparoscopic (CL) and single incision laparoscopic
      (SIL) right hemicolectomy (RHC). METHODS: This retrospective study included the
      initial 35 cases in each group. Learning curves were evaluated by the moving
      average of operative time, mean operative time of every five consecutive cases,
      and cumulative sum (CUSUM) analysis. The learning phase was considered overcome
      when the moving average of operative times reached a plateau, and when the mean
      operative time of every five consecutive cases reached a low point and
      subsequently did not vary by more than 30 minutes. RESULTS: Six patients with
      missing data in the CL RHC group were excluded from the analyses. According to
      the mean operative time of every five consecutive cases, learning phase of SIL
      and CL RHC was completed between 26 and 30 cases, and 16 and 20 cases,
      respectively. Moving average analysis revealed that approximately 31 (SIL) and 25
      (CL) cases were needed to complete the learning phase, respectively. CUSUM
      analysis demonstrated that 10 (SIL) and two (CL) cases were required to reach a
      steady state of complication-free performance, respectively. Postoperative
      complications rate was higher in SIL than in CL group, but the difference was not
      statistically significant (17.1% vs. 3.4%). CONCLUSION: The learning phase of SIL
      RHC is longer than that of CL RHC. Early oncological outcomes of both techniques
      were comparable. However, SIL RHC had a statistically insignificant higher
      complication rate than CL RHC during the learning phase.

PMID- 25960991
TI  - Noninvasive monitoring of mouse renal allograft rejection using micro-CT.
AB  - PURPOSE: Acute renal graft rejection can only be definitively diagnosed by renal
      biopsy. However, biopsies carry a risk of renal transplant injury and loss. Micro
      CT is widely used in preclinical studies of small animals. Here, we propose micro
      CT could noninvasively monitor and evaluate renal location and function in a
      mouse kidney transplant model. METHODS: Orthotopic kidney transplantation was
      performed in a BALB/c -to- C57BL/6j or C57BL/6j-to- C57BL/6j mouse model. After
      optimizing imaging techniques, five mice were imaged with micro-CT and the
      findings were verified histologically. RESULTS: Micro-CT can monitor and evaluate
      renal location and function after orthotopic kidney transplantation. There were
      no mice deaths while renal transplants were failure. CONCLUSION: We propose that
      graft micro-CT imaging is a new option that is noninvasive and specific, and can
      aid in early detection and follow-up of acute renal rejection. This method is
      potentially useful to improve posttransplant rejection monitoring.

PMID- 25960992
TI  - Evaluation of diagnostic biomarkers for acute kidney injury in major burn
      patients.
AB  - PURPOSE: Acute kidney injury (AKI) in major burn patients is a common
      complication with high morbidity and mortality. The mainstream treatment is early
      diagnosis and rapid termination and prevention of the underlying insult.
      Therefore, it's essential to identify early biomarkers predicting AKI. METHODS: A
      total of 85 patients who were admitted to the burn intensive care unit from June
      2012 to July 2013 were included in this prospective cohort study. Ten biomarkers
      (blood urea nitrogen, serum creatinine, urine creatinine, cystatin C, cystatin C
      glomerular filtration rate, AST, lacate dehydrogenase [LD], creatine kinase,
      lactic acid, and myoglobin) were obtained at time of admission and evaluated as
      diagnostic biomarkers to predicting AKI and early AKI. RESULTS: Out of 85
      patients, 35 patients were dead and overall mortality was 41.2%. The mean age was
      49.4 years and mean percentage of total body surface area was 53.2%. Area under
      the curve (AUC) of receiver operating characteristic curve of biomarkers on
      predicting AKI were 0.746, 0.718, and 0.717 in LD, lactic acid, and serum
      creatinine, respectively. AUC of cystatin C predicting AKI was much lower at
      0.555. AUC of biomarkers on predicting early AKI were 0.833, 0.816, 0.790, and
      0.759 in LD, serum creatinine, AST, and serum myoglobin. CONCLUSION: LD, lactic
      acid and serum creatinine were acceptable as diagnostic biomarkers of AKI and LD,
      serum creatinine, AST, and serum myoglobin were reasonable as diagnostic
      biomarkers of early AKI. However, cystatin C was an unfavorable biomarker in
      major burn patients.

PMID- 25960993
TI  - Giant malignant insulinoma.
AB  - Insulinomas are the most common pancreatic neuroendocrine tumors. Most
      insulinomas are benign, small, intrapancreatic solid tumors and only large tumors
      have a tendency for malignancy. Most patients present with symptoms of
      hypoglycemia that are relieved with the administration of glucose. We herein
      present the case of a 75-year-old woman who presented with an acute hypoglycemic
      episode. Subsequent laboratory and radiological studies established the diagnosis
      of a 17-cm malignant insulinoma, with local invasion to the left kidney, lymph
      node metastasis, and hepatic metastases. Patient symptoms, diagnostic and imaging
      work-up and surgical management of both the primary and the metastatic disease
      are reviewed. 

PMID- 25960994
TI  - Large cutaneous apocrine carcinoma occurring on right thigh aggravated after moxa
      treatment.
AB  - Primary cutaneous apocrine carcinoma is a rare adnexal tumor of the skin that
      occurs mainly in the axilla, anogenital area while the scalp and the lower
      extremities, especially the thigh, are very unusual sites. However, clinical or
      pathologic characteristics have not been well established due to a paucity of
      this tumor. Herein, we report very unusual case of apocrine carcinoma present as
      a huge mass in the lateral thigh of 77-year-old woman, which was aggravated
      abruptly after an irritation by moxa treatment, with a brief review of the
      literature. 

PMID- 25960995
TI  - Expression of Multidrug Resistance Transporter ABCB5 in a Murine Model of Human
      Conjunctival Melanoma.
AB  - Conjunctival melanoma (CM) is a rare ocular malignancy with a high tendency to
      reoccur locally and with a high risk of metastatic disease. Metastases are often
      unresponsive to conventional treatment. Recently, an animal model was set up
      using human CM cells. Orthotopic xenografts from human CM were created by
      subconjunctival injection of three different CM cell lines into NOD.Cg-Prkdcscid
      IL2rgtm1Wjl /SzJ (NSG) mice. Subconjunctival injection of cultured CM cells led
      to excellent subconjunctival growth, but no metastases were found. When single
      cell suspensions were obtained from the subconjunctival xenografts and passaged
      in vivo, all mice developed metastases. As recent findings indicate that cancer
      stem cells are linked to tumor recurrences, we used this new murine model to
      determine the expression of the stem cell marker ABCB5 during tumor progression.
      Expression of the ABCB5 protein was determined in three cell lines and during
      different stages of tumor development as observed in our model. All three cell
      lines contained a subpopulation of cells positive for ABCB5. During tumor
      development, expression of ABCB5 increased during phases of tumor expansion.
      Furthermore, expression of ABCB5 was increased in metastases. Using this model
      for CM, we were able to initiate metastatic spread and determine the expression
      of the stem cell marker ABCB5 during different stages of tumor development,
      identifying ABCB5 as a potential novel therapeutic target. This study illustrates
      the potential of our newly established murine model.

PMID- 25960996
TI  - Treatment of ureterosciatic hernia with a ureteral stent.
AB  - A 92-year-old woman was referred to our hospital from a family practice with the
      chief of complaint of vomiting. Subsequent computed tomography imaging revealed
      left hydroureteronephrosis without clear evidence of ureteral stones or ureteral
      tumors and that the lower part of the ureter was shifted to the outside of the
      cavum pelvis minor from the greater sciatic foramen. Retrograde pyelography was
      performed, and the shadow of a mass, which constricted and obstructed the distal
      left ureter, was observed. The patient was diagnosed with ureterosciatic hernia,
      and a left retrograde ureteral stent was indwelled and the hernia was repaired.
      Cases of ureterosciatic hernia are very rare. We describe one case of
      ureterosciatic hernia and review the relevant literature. 

PMID- 25960997
TI  - A possible clue for the production of anti-glomerular basement membrane antibody
      associated with ureteral obstruction and hydronephrosis.
AB  - BACKGROUND: Anti-glomerular basement membrane (anti-GBM) antibody-mediated
      glomerulonephritis (anti-GBM GN) is an autoimmune disease with rapidly
      progressive glomerulonephritis. Based on a case report of anti-GBM GN following
      hydronephrosis, we hypothesized that hydronephrosis may act as a trigger for the
      development of anti-GBM antibodies. PATIENTS AND METHODS: We evaluated 11
      patients who were diagnosed with hydronephrosis. It was measured with serum anti
      GBM antibody. These patients' medical histories as well as risk factors for the
      development of anti-GBM antibodies and causes of hydronephrosis were reviewed.
      Renal function and hematuria were also considered. The serum anti-GBM antibody
      was measured with enzyme-linked immunosorbent assays (ELISA) or chemiluminescent
      enzyme immunoassays (CLEIA). Histopathological findings of renal biopsy specimens
      were also evaluated. RESULTS: No patient had a medical history of renal disease.
      Five patients had a history of smoking. Ten of the 11 patients had renal
      dysfunction as evidenced by serum creatinine levels of 0.85-13.8 mg/dl, while 8
      patients had RBCs in their urinary sediment at the time of diagnosis for
      hydronephrosis. Two of the patients assessed by ELISA and CLEIA were positive for
      anti-GBM antibodies. In 1 of these 3 patients, anti-GBM antibodies and renal
      dysfunction improved upon treatment for hydronephrosis. Another of the 3 patients
      developed anti-GBM GN, but anti-GBM antibodies and renal dysfunction improved
      dramatically upon treatment. In the 3rd patient without improved hydronephrosis,
      anti-GBM antibodies and renal dysfunction remained unchanged. CONCLUSION: Our
      results provide insights into the development of anti-GBM antibodies in patients
      with ureteral obstruction and hydronephrosis.

PMID- 25960999
TI  - Mathematical modeling of subthreshold resonant properties in pyloric dilator
      neurons.
AB  - Various types of neurons exhibit subthreshold resonance oscillation (preferred
      frequency response) to fluctuating sinusoidal input currents. This phenomenon is
      well known to influence the synaptic plasticity and frequency of neural network
      oscillation. This study evaluates the resonant properties of pacemaker pyloric
      dilator (PD) neurons in the central pattern generator network through
      mathematical modeling. From the pharmacological point of view, calcium currents
      cannot be blocked in PD neurons without removing the calcium-dependent potassium
      current. Thus, the effects of calcium (I(Ca)) and calcium-dependent potassium
      (I(KCa)) currents on resonant properties remain unclear. By taking advantage of
      Hodgkin-Huxley-type model of neuron and its equivalent RLC circuit, we examine
      the effects of changing resting membrane potential and those ionic currents on
      the resonance. Results show that changing the resting membrane potential
      influences the amplitude and frequency of resonance so that the strength of
      resonance (Q-value) increases by both depolarization and hyperpolarization of the
      resting membrane potential. Moreover, hyperpolarization-activated inward current
      (I(h)) and I(Ca) (in association with I(KCa)) are dominant factors on resonant
      properties at hyperpolarized and depolarized potentials, respectively. Through
      mathematical analysis, results indicate that I h and I(KCa) affect the resonant
      properties of PD neurons. However, I(Ca) only has an amplifying effect on the
      resonance amplitude of these neurons.

PMID- 25960998
TI  - SNCA Gene, but Not MAPT, Influences Onset Age of Parkinson's Disease in Chinese
      and Australians.
AB  - BACKGROUND: alpha-Synuclein (SNCA) and microtubule-associated protein tau (MAPT)
      are the two major genes independently, but not jointly, associated with
      susceptibility for Parkinson's disease (PD). The SNCA gene has recently been
      identified as a major modifier of age of PD onset. Whether MAPT gene
      synergistically influences age of onset of PD is unknown. Objective. To
      investigate independent and joint effects of MAPT and SNCA on PD onset age.
      METHODS: 412 patients with PD were recruited from the Australian PD Research
      Network (123) and the Neurology Department, Ruijin Hospital Affiliated to
      Shanghai Jiaotong University, China (289). MAPT (rs17650901) tagging H1/H2
      haplotype and SNCA (Rep1) were genotyped in the Australian cohort, and MAPT
      (rs242557, rs3744456) and SNCA (rs11931074, rs894278) were genotyped in the
      Chinese cohort. SPSS regression analysis was used to test genetic effects on age
      at onset of PD in each cohort. RESULTS: SNCA polymorphisms associated with the
      onset age of PD in both populations. MAPT polymorphisms did not enhance such
      association in either entire cohort. CONCLUSION: This study suggests that, in
      both ethnic groups, SNCA gene variants influence the age at onset of PD and alpha
      synuclein plays a key role in the disease course of PD.

PMID- 25961000
TI  - 1,25-Dihydroxyvitamin D3 Promotes High Glucose-Induced M1 Macrophage Switching to
      M2 via the VDR-PPARgamma Signaling Pathway.
AB  - Macrophages, especially their activation state, are closely related to the
      progression of diabetic nephropathy. Classically activated macrophages (M1) are
      proinflammatory effectors, while alternatively activated macrophages (M2) exhibit
      anti-inflammatory properties. 1,25-Dihydroxyvitamin D3 has renoprotective roles
      that extend beyond the regulation of mineral metabolism, and PPARgamma, a nuclear
      receptor, is essential for macrophage polarization. The present study
      investigates the effect of 1,25-dihydroxyvitamin D3 on macrophage activation
      state and its underlying mechanism in RAW264.7 cells. We find that, under high
      glucose conditions, RAW264.7 macrophages tend to switch to the M1 phenotype,
      expressing higher iNOS and proinflammatory cytokines, including TNFalpha and IL
      12. While 1,25-dihydroxyvitamin D3 significantly inhibited M1 activation, it
      enhanced M2 macrophage activation; namely, it upregulated the expression of MR,
      Arg-1, and the anti-inflammatory cytokine IL-10 but downregulated the M1 markers.
      However, the above effects of 1,25-dihydroxyvitamin D3 were abolished when the
      expression of VDR and PPARgamma was inhibited by VDR siRNA and a PPARgamma
      antagonist. In addition, PPARgamma was also decreased upon treatment with VDR
      siRNA. The above results demonstrate that active vitamin D promoted M1 phenotype
      switching to M2 via the VDR-PPARgamma pathway. 

PMID- 25961001
TI  - Risk factors for delayed inpatient functional recovery after total knee
      arthroplasty.
AB  - PURPOSE: To determine the predictive value of surgery-related variables for
      delayed inpatient functional recovery (i.e., >=3 days to reach functional
      independence) after TKA. METHOD: 193 consecutive people undergoing TKA were
      included in this prospective cohort study. Inpatient functional recovery was
      measured daily using the Iowa Level of Assistance scale (ILAS). Two persons
      reviewed medical records to extract patient characteristics (i.e., age, sex, and
      BMI) and surgical factors (i.e., blood loss, tourniquet time, postoperative
      morphine use, and surgical experience). Odds ratios (OR) and area under the
      curves (AUC) were calculated to determine the predictive value of the putative
      factors and of the model on delayed functional recovery, respectively. RESULTS:
      Delayed functional recovery was apparent in 76 (39%) people. Higher age, female
      sex, and higher BMI were all independent risk factors for delayed functional
      recovery (AUC (95%-CI); 0.72 (0.65-0.80)), whereas blood loss (OR (95%-CI); 1.00
      (0.99-1.01)), tourniquet time (OR = 1.00 (0.98-1.02)), and postoperative morphine
      use (OR = 0.88 (0.37-2.06)) did not statistically improve the predictive value of
      the model, while surgical experience did (OR = 0.31 (0.16-0.64); AUC = 0.76 (0.69
      83)). CONCLUSIONS: Surgery-related factors contribute little to the patient
      related characteristics in a predictive model explaining delayed functional
      recovery after TKA in daily orthopaedic practice.

PMID- 25961002
TI  - Relation between Body Structure and Hearing during Soft Tissue Auditory
      Stimulation.
AB  - Hearing is elicited by applying the clinical bone vibrator to soft tissue sites
      on the head, neck, and thorax. Two mapping experiments were conducted in normal
      hearing subjects differing in body build: determination of the lowest soft tissue
      stimulation site at which a 60 dB SL tone at 2.0 kHz was effective in eliciting
      auditory sensation and assessment of actual thresholds along the midline of the
      head, neck, and back. In males, a lower site for hearing on the back was strongly
      correlated with a leaner body build. A correlation was not found in females. In
      both groups, thresholds on the head were lower, and they were higher on the back,
      with a transition along the neck. This relation between the soft tissue
      stimulation site and hearing sensation is likely due to the different
      distribution of soft tissues in various parts of the body.

PMID- 25961003
TI  - Biomarker identification and pathway analysis by serum metabolomics of lung
      cancer.
AB  - Lung cancer is one of the most common causes of cancer death, for which no
      validated tumor biomarker is sufficiently accurate to be useful for diagnosis.
      Additionally, the metabolic alterations associated with the disease are unclear.
      In this study, we investigated the construction, interaction, and pathways of
      potential lung cancer biomarkers using metabolomics pathway analysis based on the
      Kyoto Encyclopedia of Genes and Genomes database and the Human Metabolome
      Database to identify the top altered pathways for analysis and visualization. We
      constructed a diagnostic model using potential serum biomarkers from patients
      with lung cancer. We assessed their specificity and sensitivity according to the
      area under the curve of the receiver operator characteristic (ROC) curves, which
      could be used to distinguish patients with lung cancer from normal subjects. The
      pathway analysis indicated that sphingolipid metabolism was the top altered
      pathway in lung cancer. ROC curve analysis indicated that glycerophospho-N
      arachidonoyl ethanolamine (GpAEA) and sphingosine were potential sensitive and
      specific biomarkers for lung cancer diagnosis and prognosis. Compared with the
      traditional lung cancer diagnostic biomarkers carcinoembryonic antigen and
      cytokeratin 19 fragment, GpAEA and sphingosine were as good or more appropriate
      for detecting lung cancer. We report our identification of potential metabolic
      diagnostic and prognostic biomarkers of lung cancer and clarify the metabolic
      alterations in lung cancer. 

PMID- 25961004
TI  - Survival rate of short, locking taper implants with a plateau design: a 5-year
      retrospective study.
AB  - BACKGROUND: Short implants have become popular in the reconstruction of jaws,
      especially in cases with limited bone height. Shorter implants, those with
      locking tapers and plateau root shapes, tend to have longer survival times. We
      retrospectively investigated the cumulative survival rates of Bicon short
      implants (<8 mm) according to patient variables over a 5-year period. MATERIALS
      AND METHODS: This study included 111 consecutively treated patients with 371
      implants supporting fixed or removable prosthetics. Data were evaluated to
      acquire cumulative survival rates according to gender, age, tobacco use, surgical
      procedure, bone quality, and restoration type. Statistics were performed using
      chi-square, Mann-Whitney, and Kruskal Wallis H tests. RESULTS: The survival rate
      was 97.3% with, on average, 22.8 months of follow-up. Patients older than 60
      years had higher failure rate than the other age groups (P < 0.05). Placed
      region, age, and bone quality had adverse effects on survival rate in the <8 mm
      implant group with statistically significant difference (P < 0.05). CONCLUSIONS:
      Approximately 23-month follow-up data indicate that short implants with locking
      tapers and plateau-type roots have comparable survival rates as other types of
      dental implants. However, due to limitations of study, these issues remain to be
      further investigated in future randomized controlled clinical trials.

PMID- 25961005
TI  - Phenotypic characteristics associated with virulence of clinical isolates from
      the Sporothrix complex.
AB  - The Sporothrix complex members cause sporotrichosis, a subcutaneous mycosis with
      a wide spectrum of clinical manifestations. Several specific phenotypic
      characteristics are associated with virulence in many fungi, but studies in this
      field involving the Sporothrix complex species are scarce. Melanization,
      thermotolerance, and production of proteases, catalase, and urease were
      investigated in 61 S. brasiliensis, one S. globosa, and 10 S. schenckii strains.
      The S. brasiliensis strains showed a higher expression of melanin and urease
      compared with S. schenckii. These two species, however, presented similar
      thermotolerances. Our S. globosa strain had low expression of all studied
      virulence factors. The relationship between these phenotypes and clinical aspects
      of sporotrichosis was also evaluated. Strains isolated from patients with
      spontaneous regression of infection were heavily melanized and produced high
      urease levels. Melanin was also related to dissemination of internal organs and
      protease production was associated with HIV-coinfection. A murine sporotrichosis
      model showed that a S. brasiliensis strain with high expression of virulence
      factors was able to disseminate and yield a high fungal burden in comparison with
      a control S. schenckii strain. Our results show that virulence-related phenotypes
      are variably expressed within the Sporothrix complex species and might be
      involved in clinical aspects of sporotrichosis. 

PMID- 25961007
TI  - Application of FTIR-ATR Spectroscopy to Determine the Extent of Lipid
      Peroxidation in Plasma during Haemodialysis.
AB  - During a haemodialysis (HD), because of the contact of blood with the surface of
      the dialyser, the immune system becomes activated and reactive oxygen species
      (ROS) are released into plasma. Particularly exposed to the ROS are lipids and
      proteins contained in plasma, which undergo peroxidation. The main breakdown
      product of oxidized lipids is the malondialdehyde (MDA). A common method for
      measuring the concentration of MDA is a thiobarbituric acid reactive substances
      (TBARS) method. Despite the formation of MDA in plasma during HD, its
      concentration decreases because it is removed from the blood in the dialyser.
      Therefore, this research proposes the Fourier Transform Infrared Attenuated Total
      Reflectance (FTIR-ATR) spectroscopy, which enables determination of primary
      peroxidation products. We examined the influence of the amount of hydrogen
      peroxide added to lipid suspension that was earlier extracted from plasma
      specimen on lipid peroxidation with use of TBARS and FTIR-ATR methods. Linear
      correlation between these methods was shown. The proposed method was effective
      during the evaluation of changes in the extent of lipid peroxidation in plasma
      during a haemodialysis in sheep. A measurement using the FTIR-ATR showed an
      increase in plasma lipid peroxidation after 15 and 240 minutes of treatment,
      while the TBARS concentration was respectively lower. 

PMID- 25961008
TI  - Dealing with stigma: experiences of persons affected by disabilities and leprosy.
AB  - Persons affected by leprosy or by disabilities face forms of stigma that have an
      impact on their lives. This study seeks to establish whether their experiences of
      stigma are similar, with a view to enabling the two groups of people to learn
      from each other. Accounts of experiences of the impact of stigma were obtained
      using in-depth interviews and focus group discussion with people affected by
      leprosy and by disabilities not related to leprosy. The analysis shows that there
      are a lot of similarities in impact of stigma in terms of emotions, thoughts,
      behaviour, and relationships between the two groups. The main difference is that
      those affected by leprosy tended to frame their situation in medical terms, while
      those living with disabilities described their situation from a more social
      perspective. In conclusion, the similarities offer opportunities for
      interventions and the positive attitudes and behaviours can be modelled in the
      sense that both groups can learn and benefit. Research that tackles different
      aspects of stigmatization faced by both groups could lead to inclusive
      initiatives that help individuals to come to terms with the stigma and to
      advocate against exclusion and discrimination. 

PMID- 25961009
TI  - Feature Selection Combined with Neural Network Structure Optimization for HIV-1
      Protease Cleavage Site Prediction.
AB  - It is crucial to understand the specificity of HIV-1 protease for designing HIV-1
      protease inhibitors. In this paper, a new feature selection method combined with
      neural network structure optimization is proposed to analyze the specificity of
      HIV-1 protease and find the important positions in an octapeptide that determined
      its cleavability. Two kinds of newly proposed features based on Amino Acid Index
      database plus traditional orthogonal encoding features are used in this paper,
      taking both physiochemical and sequence information into consideration. Results
      of feature selection prove that p2, p1, p1', and p2' are the most important
      positions. Two feature fusion methods are used in this paper: combination fusion
      and decision fusion aiming to get comprehensive feature representation and
      improve prediction performance. Decision fusion of subsets that getting after
      feature selection obtains excellent prediction performance, which proves feature
      selection combined with decision fusion is an effective and useful method for the
      task of HIV-1 protease cleavage site prediction. The results and analysis in this
      paper can provide useful instruction and help designing HIV-1 protease inhibitor
      in the future. 

PMID- 25961010
TI  - Induction of Ankrd1 in Dilated Cardiomyopathy Correlates with the Heart Failure
      Progression.
AB  - Progression of idiopathic dilated cardiomyopathy (IDCM) is marked with extensive
      left ventricular remodeling whose clinical manifestations and molecular basis are
      poorly understood. We aimed to evaluate the clinical potential of titin ligands
      in monitoring progression of cardiac remodeling associated with end-stage IDCM.
      Expression patterns of 8 mechanoptotic machinery-associated titin ligands
      (ANKRD1, ANKRD2, TRIM63, TRIM55, NBR1, MLP, FHL2, and TCAP) were quantitated in
      endomyocardial biopsies from 25 patients with advanced IDCM. When comparing NYHA
      disease stages, elevated ANKRD1 expression levels marked transition from NYHA <
      IV to NYHA IV. ANKRD1 expression levels closely correlated with systolic strain
      depression and short E wave deceleration time, as determined by echocardiography.
      On molecular level, myocardial ANKRD1 and serum adiponectin correlated with low
      BAX/BCL-2 ratios, indicative of antiapoptotic tissue propensity observed during
      the worsening of heart failure. ANKRD1 is a potential marker for cardiac
      remodeling and disease progression in IDCM. ANKRD1 expression correlated with
      reduced cardiac contractility and compliance. The association of ANKRD1 with
      antiapoptotic response suggests its role as myocyte survival factor during late
      stage heart disease, warranting further studies on ANKRD1 during end-stage heart
      failure. 

PMID- 25961011
TI  - DNA methylation and histone modifications are the molecular lock in lentivirally
      transduced hematopoietic progenitor cells.
AB  - Stable introduction of a functional gene in hematopoietic progenitor cells (HPCs)
      has appeared to be an alternative approach to correct genetically linked blood
      diseases. However, it is still unclear whether lentiviral vector (LV) is
      subjected to gene silencing in HPCs. Here, we show that LV carrying green
      fluorescent protein (GFP) reporter gene driven by cytomegalovirus (CMV) promoter
      was subjected to transgene silencing after transduction into HPCs. This
      phenomenon was not due to the deletion of proviral copy number. Study using DNA
      demethylating agent and histone deacetylase (HDAC) inhibitor showed that the
      drugs could either prevent or reverse the silencing effect. Using sodium
      bisulfite sequencing and chromatin immunoprecipitation (ChIP) assay, we
      demonstrated that DNA methylation occurred soon after LV transduction. At the
      highest level of gene expression, CMV promoter was acetylated and was in a
      euchromatin state, while GFP reporter gene was acetylated but was strangely in a
      heterochromatin state. When the expression declined, CMV promoter underwent
      transition from acetylated and euchromatic state to a heterochromatic state,
      while the GFP reporter gene was in deacetylated and heterochromatic state. With
      these, we verify that DNA methylation and dynamic histone modifications lead to
      transgene silencing in HPCs transduced with LV. 

PMID- 25961006
TI  - Poorly understood aspects of striated muscle contraction.
AB  - Muscle contraction results from cyclic interactions between the contractile
      proteins myosin and actin, driven by the turnover of adenosine triphosphate
      (ATP). Despite intense studies, several molecular events in the contraction
      process are poorly understood, including the relationship between force
      generation and phosphate-release in the ATP-turnover. Different aspects of the
      force-generating transition are reflected in the changes in tension development
      by muscle cells, myofibrils and single molecules upon changes in temperature,
      altered phosphate concentration, or length perturbations. It has been notoriously
      difficult to explain all these events within a given theoretical framework and to
      unequivocally correlate observed events with the atomic structures of the myosin
      motor. Other incompletely understood issues include the role of the two heads of
      myosin II and structural changes in the actin filaments as well as the importance
      of the three-dimensional order. We here review these issues in relation to
      controversies regarding basic physiological properties of striated muscle. We
      also briefly consider actomyosin mutation effects in cardiac and skeletal muscle
      function and the possibility to treat these defects by drugs. 

PMID- 25961012
TI  - The Differential Proteome of the Probiotic Lactobacillus acidophilus NCFM Grown
      on the Potential Prebiotic Cellobiose Shows Upregulation of Two beta -Glycoside
      Hydrolases.
AB  - Probiotics, prebiotics, and combinations thereof, that is, synbiotics, are known
      to exert beneficial health effects in humans; however interactions between pro-
      and prebiotics remain poorly understood at the molecular level. The present study
      describes changes in abundance of different proteins of the probiotic bacterium
      Lactobacillus acidophilus NCFM (NCFM) when grown on the potential prebiotic
      cellobiose as compared to glucose. Cytosolic cell extract proteomes after harvest
      at late exponential phase of NCFM grown on cellobiose or glucose were analyzed by
      two dimensional difference gel electrophoresis (2D-DIGE) in the acidic (pH 4-7)
      and the alkaline (pH 6-11) regions showing a total of 136 spots to change in
      abundance. Proteins were identified by MS or MS/MS from 81 of these spots
      representing 49 unique proteins and either increasing 1.5-13.9-fold or decreasing
      1.5-7.8-fold in relative abundance. Many of these proteins were associated with
      energy metabolism, including the cellobiose related glycoside hydrolases phospho
      beta-glucosidase (LBA0881) and phospho-beta-galactosidase II (LBA0726). The data
      provide insight into the utilization of the candidate prebiotic cellobiose by the
      probiotic bacterium NCFM. Several of the upregulated or downregulated identified
      proteins associated with utilization of cellobiose indicate the presence of
      carbon catabolite repression and regulation of enzymes involved in carbohydrate
      metabolism. 

PMID- 25961013
TI  - Relationship between Hyperuricemia and Haar-Like Features on Tongue Images.
AB  - OBJECTIVE: To investigate differences in tongue images of subjects with and
      without hyperuricemia. MATERIALS AND METHODS: This population-based case-control
      study was performed in 2012-2013. We collected data from 46 case subjects with
      hyperuricemia and 46 control subjects, including results of biochemical
      examinations and tongue images. Symmetrical Haar-like features based on integral
      images were extracted from tongue images. T-tests were performed to determine the
      ability of extracted features to distinguish between the case and control groups.
      We first selected features using the common criterion P < 0.05, then conducted
      further examination of feature characteristics and feature selection using means
      and standard deviations of distributions in the case and control groups. RESULTS:
      A total of 115,683 features were selected using the criterion P < 0.05. The
      maximum area under the receiver operating characteristic curve (AUC) of these
      features was 0.877. The sensitivity of the feature with the maximum AUC value was
      0.800 and specificity was 0.826 when the Youden index was maximized. Features
      that performed well were concentrated in the tongue root region. CONCLUSIONS:
      Symmetrical Haar-like features enabled discrimination of subjects with and
      without hyperuricemia in our sample. The locations of these discriminative
      features were in agreement with the interpretation of tongue appearance in
      traditional Chinese and Western medicine.

PMID- 25961015
TI  - Prediction of antifungal activity of gemini imidazolium compounds.
AB  - The progress of antimicrobial therapy contributes to the development of strains
      of fungi resistant to antimicrobial drugs. Since cationic surfactants have been
      described as good antifungals, we present a SAR study of a novel homologous
      series of 140 bis-quaternary imidazolium chlorides and analyze them with respect
      to their biological activity against Candida albicans as one of the major
      opportunistic pathogens causing a wide spectrum of diseases in human beings. We
      characterize a set of features of these compounds, concerning their structure,
      molecular descriptors, and surface active properties. SAR study was conducted
      with the help of the Dominance-Based Rough Set Approach (DRSA), which involves
      identification of relevant features and relevant combinations of features being
      in strong relationship with a high antifungal activity of the compounds. The SAR
      study shows, moreover, that the antifungal activity is dependent on the type of
      substituents and their position at the chloride moiety, as well as on the surface
      active properties of the compounds. We also show that molecular descriptors
      MlogP, HOMO-LUMO gap, total structure connectivity index, and Wiener index may be
      useful in prediction of antifungal activity of new chemical compounds. 

PMID- 25961014
TI  - Diabetes and its link with cancer: providing the fuel and spark to launch an
      aggressive growth regime.
AB  - Diabetes is a disease involving metabolic derangements in multiple organs. While
      the spectrum of diabetic complications has been known for years, recent evidence
      suggests that diabetes could also contribute to the initiation and propagation of
      certain cancers. The mechanism(s) underlying this relationship are not completely
      resolved but likely involve changes in hormone and nutrient levels, as well as
      activation of inflammatory and stress-related pathways. Interestingly, some of
      the drugs used clinically to treat diabetes also appear to have antitumour
      effects, further highlighting the interaction between these two conditions. In
      this contribution we review recent literature on this emerging relationship and
      explore the potential mechanisms that may promote cancer in diabetic patients. 

PMID- 25961017
TI  - Home-Based versus Hospital-Based Rehabilitation Program after Total Knee
      Replacement.
AB  - OBJECTIVES: To compare home-based rehabilitation with the standard hospital
      rehabilitation in terms of improving knee joint mobility and recovery of muscle
      strength and function in patients after a total knee replacement. MATERIALS AND
      METHODS: A non-randomised controlled trial was conducted. Seventy-eight patients
      with a prosthetic knee were included in the study and allocated to either a home
      based or hospital-based rehabilitation programme. Treatment included various
      exercises to restore strength and joint mobility and to improve patients'
      functional capacity. The primary outcome of the trial was the treatment
      effectiveness measured by the Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC). RESULTS: The groups did not significantly differ in
      the leg side (right/left) or clinical characteristics (P > 0.05). After the
      intervention, both groups showed significant improvements (P < 0.001) from the
      baseline values in the level of pain (visual analogue scale), the range of
      flexion-extension motion and muscle strength, disability (Barthel and WOMAC
      indices), balance, and walking. CONCLUSIONS: This study reveals that the
      rehabilitation treatments offered either at home or in hospital settings are
      equally effective.

PMID- 25961016
TI  - Low Frequency Electromagnetic Field Conditioning Protects against I/R Injury and
      Contractile Dysfunction in the Isolated Rat Heart.
AB  - Low frequency electromagnetic field (LF-EMF) decreases the formation of reactive
      oxygen species, which are key mediators of ischemia/reperfusion (I/R) injury.
      Therefore, we hypothesized that the LF-EMF protects contractility of hearts
      subjected to I/R injury. Isolated rat hearts were subjected to 20 min of global
      no-flow ischemia, followed by 30 min reperfusion, in the presence or absence of
      LF-EMF. Coronary flow, heart rate, left ventricular developed pressure (LVDP),
      and rate pressure product (RPP) were determined for evaluation of heart
      mechanical function. The activity of cardiac matrix metalloproteinase-2 (MMP-2)
      and the contents of coronary effluent troponin I (TnI) and interleukin-6 (IL-6)
      were measured as markers of heart injury. LF-EMF prevented decreased RPP in I/R
      hearts, while having no effect on coronary flow. In addition, hearts subjected to
      I/R exhibited significantly increased LVDP when subjected to LF-EMF. Although TnI
      and IL-6 levels were increased in I/R hearts, their levels returned to baseline
      aerobic levels in I/R hearts subjected to LF-EMF. The reduced activity of MMP-2
      in I/R hearts was reversed in hearts subjected to LF-EMF. The data presented here
      indicate that acute exposure to LF-EMF protects mechanical function of I/R hearts
      and reduces I/R injury.

PMID- 25961018
TI  - The Effect of LAB as Probiotic Starter Culture and Green Tea Extract Addition on
      Dry Fermented Pork Loins Quality.
AB  - The objective of this study was to evaluate the microbiological, physicochemical,
      and sensory quality of dry fermented pork loin produced with the addition of Lb.
      rhamnosus LOCK900 probiotic strain, 0.2% glucose, and 1.5% green tea extract.
      Three loins were prepared: control sample (P0: no additives), sample supplemented
      with glucose and probiotic strain (P1), and sample with glucose, green tea
      extract, and probiotic (P2). The samples were analyzed after 21 days of ripening
      and 180 days of storage. The results indicated that the highest count of LAB was
      observed both in the samples: with probiotic and with probiotic and green tea
      extract (7.00 log cfu/g after ripening; 6.00 log cfu/g after storage). The
      oxidation-reduction potential values were lower in the probiotic loin samples.
      Probiotic and green tea extract have not caused color changes of study loins
      during storage. The study demonstrated that an addition of probiotic and green
      tea extract to dry fermented loins is possible and had no impact on sensory
      quality after product storage. 

PMID- 25961019
TI  - High order gene-gene interactions in eight single nucleotide polymorphisms of
      renin-angiotensin system genes for hypertension association study.
AB  - Several single nucleotide polymorphisms (SNPs) of renin-angiotensin system (RAS)
      genes are associated with hypertension (HT) but most of them are focusing on
      single locus effects. Here, we introduce an unbalanced function based on
      multifactor dimensionality reduction (MDR) for multiloci genotypes to detect high
      order gene-gene (SNP-SNP) interaction in unbalanced cases and controls of HT
      data. Eight SNPs of three RAS genes (angiotensinogen, AGT; angiotensin-converting
      enzyme, ACE; angiotensin II type 1 receptor, AT 1 R) in HT and non-HT subjects
      were included that showed no significant genotype differences. In 2- to 6-locus
      models of the SNP-SNP interaction, the SNPs of AGT and ACE genes were associated
      with hypertension (bootstrapping odds ratio [Boot-OR] = 1.972~3.785; 95%,
      confidence interval (CI) 1.26~6.21; P < 0.005). In 7- and 8-locus model, SNP
      A1166C of AT 1 R gene is joined to improve the maximum Boot-OR values of 4.050 to
      4.483; CI = 2.49 to 7.29; P < 1.63E - 08. In conclusion, the epistasis networks
      are identified by eight SNP-SNP interaction models. AGT, ACE, and AT 1 R genes
      have overall effects with susceptibility to hypertension, where the SNPs of ACE
      have a mainly hypertension-associated effect and show an interacting effect to
      SNPs of AGT and AT 1 R genes. 

PMID- 25961020
TI  - Dissociation of Calcium Transients and Force Development following a Change in
      Stimulation Frequency in Isolated Rabbit Myocardium.
AB  - As the heart transitions from one exercise intensity to another, changes in
      cardiac output occur, which are modulated by alterations in force development and
      calcium handling. Although the steady-state force-calcium relationship at various
      heart rates is well investigated, regulation of these processes during
      transitions in heart rate is poorly understood. In isolated right ventricular
      muscle preparations from the rabbit, we investigated the beat-to-beat alterations
      in force and calcium during the transition from one stimulation frequency to
      another, using contractile assessments and confocal microscopy. We show that a
      change in steady-state conditions occurs in multiple phases: a rapid phase, which
      is characterized by a fast change in force production mirrored by a change in
      calcium transient amplitude, and a slow phase, which follows the rapid phase and
      occurs as the muscle proceeds to stabilize at the new frequency. This second/late
      phase is characterized by a quantitative dissociation between the calcium
      transient amplitude and developed force. Twitch timing kinetics, such as time to
      peak tension and 50% relaxation rate, reached steady-state well before force
      development and calcium transient amplitude. The dynamic relationship between
      force and calcium upon a switch in stimulation frequency unveils the dynamic
      involvement of myofilament-based properties in frequency-dependent activation. 

PMID- 25961021
TI  - Identification of Novel Potential Vaccine Candidates against Tuberculosis Based
      on Reverse Vaccinology.
AB  - Tuberculosis (TB) is a chronic infectious disease, considered as the second
      leading cause of death worldwide, caused by Mycobacterium tuberculosis. The
      limited efficacy of the bacillus Calmette-Guerin (BCG) vaccine against pulmonary
      TB and the emergence of multidrug-resistant TB warrants the need for more
      efficacious vaccines. Reverse vaccinology uses the entire proteome of a pathogen
      to select the best vaccine antigens by in silico approaches. M. tuberculosis
      H37Rv proteome was analyzed with NERVE (New Enhanced Reverse Vaccinology
      Environment) prediction software to identify potential vaccine targets; these 331
      proteins were further analyzed with VaxiJen for the determination of their
      antigenicity value. Only candidates with values >=0.5 of antigenicity and 50% of
      adhesin probability and without homology with human proteins or transmembrane
      regions were selected, resulting in 73 antigens. These proteins were grouped by
      families in seven groups and analyzed by amino acid sequence alignments,
      selecting 16 representative proteins. For each candidate, a search of the
      literature and protein analysis with different bioinformatics tools, as well as a
      simulation of the immune response, was conducted. Finally, we selected six novel
      vaccine candidates, EsxL, PE26, PPE65, PE_PGRS49, PBP1, and Erp, from M.
      tuberculosis that can be used to improve or design new TB vaccines. 

PMID- 25961022
TI  - {2-[1-(3-Methoxycarbonylmethyl-1H-indol-2-yl)-1-methyl-ethyl]-1H-indol-3-yl}
      acetic Acid Methyl Ester Inhibited Hepatocellular Carcinoma Growth in Bel-7402
      Cells and Its Resistant Variants by Activation of NOX4 and SIRT3.
AB  - {2-[1-(3-Methoxycarbonylmethyl-1H-indol-2-yl)-1-methyl-ethyl]-1H-indol-3-yl}
      acetic acid methyl ester (MIAM) is a novel indole compound, which possessed high
      efficacy against many cancers xenografted in mice without obvious toxicity. In
      this study, we aimed to investigate the effects of MIAM on human hepatocellular
      carcinoma (HCC) Bel-7402 cells and its resistant variants Bel-7402/5FU. MIAM
      inhibited the growth of HCC more potent in Bel-7402/5FU cells than its parent
      cells. MIAM increased cellular reactive oxygen species (ROS) levels, induced cell
      apoptosis, and arrested cell cycle in G0/G1 phase. MIAM might exert its action on
      Bel-7402/5FU cells through activation of NADPH oxidase 4 (NOX4)/p22(phox),
      Sirtuin3 (SIRT3)/SOD2, and SIRT3/p53/p21(Waf1/Cip) pathways. MIAM might inhibit
      HCC growth through the modulation of SIRT3. When SIRT3 was silenced, the
      inhibitory effect of MIAM on Bel-7402/5FU was lowered, showing the characteristic
      of resistance against MIAM, whereas Bel-7402/5FU cells with high expression of
      SIRT3 by SIRT3 adenovirus infection demonstrated the high sensitivity to MIAM.
      These results suggested that MIAM might exert its action against Bel-7402/5FU
      growth through upregulation of SIRT3. We suggested that MIAM might be a promising
      candidate compound which could develop as a potent anticancer agent targeting
      NOX4 and SIRT3 activation. 

PMID- 25961023
TI  - Transcriptomic Analysis of mRNAs in Human Monocytic Cells Expressing the HIV-1
      Nef Protein and Their Exosomes.
AB  - The Nef protein of human immunodeficiency virus (HIV) promotes viral replication
      and progression to AIDS. Besides its well-studied effects on intracellular
      signaling, Nef also functions through its secretion in exosomes, which are
      nanovesicles containing proteins, microRNAs, and mRNAs and are important for
      intercellular communication. Nef expression enhances exosome secretion and these
      exosomes can enter uninfected CD4 T cells leading to apoptotic death. We have
      recently reported the first miRNome analysis of exosomes secreted from Nef
      expressing U937monocytic cells. Here we show genome-wide transcriptome analysis
      of Nef-expressing U937 cells and their exosomes. We identified four key mRNAs
      preferentially retained in Nef-expressing cells; these code for MECP2, HMOX1,
      AARSD1, and ATF2 and are important for chromatin modification and gene
      expression. Interestingly, their target miRNAs are exported out in exosomes. We
      also identified three key mRNAs selectively secreted in exosomes from Nef
      expressing U937 cells and their corresponding miRNAs being preferentially
      retained in cells. These are AATK, SLC27A1, and CDKAL and are important in
      apoptosis and fatty acid transport. Thus, our study identifies selectively
      expressed mRNAs in Nef-expressing U937 cells and their exosomes and supports a
      new mode on intercellular regulation by the HIV-1 Nef protein. 

PMID- 25961024
TI  - Analysis of Coinfections with A/H1N1 Strain Variants among Pigs in Poland by
      Multitemperature Single-Strand Conformational Polymorphism.
AB  - Monitoring and control of infections are key parts of surveillance systems and
      epidemiological risk prevention. In the case of influenza A viruses (IAVs), which
      show high variability, a wide range of hosts, and a potential of reassortment
      between different strains, it is essential to study not only people, but also
      animals living in the immediate surroundings. If understated, the animals might
      become a source of newly formed infectious strains with a pandemic potential.
      Special attention should be focused on pigs, because of the receptors specific
      for virus strains originating from different species, localized in their
      respiratory tract. Pigs are prone to mixed infections and may constitute a
      reservoir of potentially dangerous IAV strains resulting from genetic
      reassortment. It has been reported that a quadruple reassortant, A(H1N1)pdm09,
      can be easily transmitted from humans to pigs and serve as a donor of genetic
      segments for new strains capable of infecting humans. Therefore, it is highly
      desirable to develop a simple, cost-effective, and rapid method for evaluation of
      IAV genetic variability. We describe a method based on multitemperature single
      strand conformational polymorphism (MSSCP), using a fragment of the hemagglutinin
      (HA) gene, for detection of coinfections and differentiation of genetic variants
      of the virus, difficult to identify by conventional diagnostic. 

PMID- 25961025
TI  - Predict and Analyze Protein Glycation Sites with the mRMR and IFS Methods.
AB  - Glycation is a nonenzymatic process in which proteins react with reducing sugar
      molecules. The identification of glycation sites in protein may provide
      guidelines to understand the biological function of protein glycation. In this
      study, we developed a computational method to predict protein glycation sites by
      using the support vector machine classifier. The experimental results showed that
      the prediction accuracy was 85.51% and an overall MCC was 0.70. Feature analysis
      indicated that the composition of k-spaced amino acid pairs feature contributed
      the most for glycation sites prediction. 

PMID- 25961026
TI  - Application of systems biology and bioinformatics methods in biochemistry and
      biomedicine 2014.

PMID- 25961027
TI  - Building a framework for a dual task taxonomy.
AB  - The study of dual task interference has gained increasing attention in the
      literature for the past 35 years, with six MEDLINE citations in 1979 growing to
      351 citations indexed in 2014 and a peak of 454 cited papers in 2013.
      Increasingly, researchers are examining dual task cost in individuals with
      pathology, including those with neurodegenerative diseases. While the influence
      of these papers has extended from the laboratory to the clinic, the field has
      evolved without clear definitions of commonly used terms and with extreme
      variations in experimental procedures. As a result, it is difficult to examine
      the interference literature as a single body of work. In this paper we present a
      new taxonomy for classifying cognitive-motor and motor-motor interference within
      the study of dual task behaviors that connects traditional concepts of learning
      and principles of motor control with current issues of multitasking analysis. As
      a first step in the process we provide an operational definition of dual task,
      distinguishing it from a complex single task. We present this new taxonomy,
      inclusive of both cognitive and motor modalities, as a working model; one that we
      hope will generate discussion and create a framework from which one can view
      previous studies and develop questions of interest. 

PMID- 25961028
TI  - mRMR-ABC: A Hybrid Gene Selection Algorithm for Cancer Classification Using
      Microarray Gene Expression Profiling.
AB  - An artificial bee colony (ABC) is a relatively recent swarm intelligence
      optimization approach. In this paper, we propose the first attempt at applying
      ABC algorithm in analyzing a microarray gene expression profile. In addition, we
      propose an innovative feature selection algorithm, minimum redundancy maximum
      relevance (mRMR), and combine it with an ABC algorithm, mRMR-ABC, to select
      informative genes from microarray profile. The new approach is based on a support
      vector machine (SVM) algorithm to measure the classification accuracy for
      selected genes. We evaluate the performance of the proposed mRMR-ABC algorithm by
      conducting extensive experiments on six binary and multiclass gene expression
      microarray datasets. Furthermore, we compare our proposed mRMR-ABC algorithm with
      previously known techniques. We reimplemented two of these techniques for the
      sake of a fair comparison using the same parameters. These two techniques are
      mRMR when combined with a genetic algorithm (mRMR-GA) and mRMR when combined with
      a particle swarm optimization algorithm (mRMR-PSO). The experimental results
      prove that the proposed mRMR-ABC algorithm achieves accurate classification
      performance using small number of predictive genes when tested using both
      datasets and compared to previously suggested methods. This shows that mRMR-ABC
      is a promising approach for solving gene selection and cancer classification
      problems. 

PMID- 25961029
TI  - Coexpression Pattern Analysis of NPM1-Associated Genes in Chronic Myelogenous
      Leukemia.
AB  - BACKGROUND: Nucleophosmin 1 (NPM1) plays an important role in ribosomal synthesis
      and malignancies, but NPM1 mutations occur rarely in the blast-crisis and chronic
      phase chronic myelogenous leukemia (CML) patients. The NPM1-associated gene set
      (GCM_NPM1), in total 116 genes including NPM1, was chosen as the candidate gene
      set for the coexpression analysis. We wonder if NPM1-associated genes can affect
      the ribosomal synthesis and translation process in CML. RESULTS: We presented a
      distribution-based approach for gene pair classification by identifying a disease
      specific cutoff point that classified the coexpressed gene pairs into strong and
      weak coexpression structures. The differences in the coexpression patterns
      between the normal and the CML groups were reflected from the overall structure
      by performing two-sample Kolmogorov-Smirnov test. Our developed method
      effectively identified the coexpression pattern differences from the overall
      structure: P  value = 1.71 * 10(-22) < 0.05 for the maximum deviation D = 0.109.
      Moreover, we found that genes involved in the ribosomal synthesis and translation
      process tended to be coexpressed in the CML group. CONCLUSION: Our developed
      method can identify the coexpression difference between two different groups.
      Dysregulation of ribosomal synthesis and translation process may be related to
      the CML disease. Our significant findings may provide useful information for the
      novel CML mechanism exploration and cancer treatment.

PMID- 25961030
TI  - Evolutionary Pattern and Regulation Analysis to Support Why Diversity Functions
      Existed within PPAR Gene Family Members.
AB  - Peroxisome proliferators-activated receptor (PPAR) gene family members exhibit
      distinct patterns of distribution in tissues and differ in functions. The purpose
      of this study is to investigate the evolutionary impacts on diversity functions
      of PPAR members and the regulatory differences on gene expression patterns. 63
      homology sequences of PPAR genes from 31 species were collected and analyzed. The
      results showed that three isolated types of PPAR gene family may emerge from
      twice times of gene duplication events. The conserved domains of HOLI (ligand
      binding domain of hormone receptors) domain and ZnF_C4 (C4 zinc finger in nuclear
      in hormone receptors) are essential for keeping basic roles of PPAR gene family,
      and the variant domains of LCRs may be responsible for their divergence in
      functions. The positive selection sites in HOLI domain are benefit for PPARs to
      evolve towards diversity functions. The evolutionary variants in the promoter
      regions and 3' UTR regions of PPARs result into differential transcription
      factors and miRNAs involved in regulating PPAR members, which may eventually
      affect their expressions and tissues distributions. These results indicate that
      gene duplication event, selection pressure on HOLI domain, and the variants on
      promoter and 3' UTR are essential for PPARs evolution and diversity functions
      acquired. 

PMID- 25961031
TI  - Impact of a Complex Food Microbiota on Energy Metabolism in the Model Organism
      Caenorhabditis elegans.
AB  - The nematode Caenorhabditis elegans is widely used as a model system for research
      on aging, development, and host-pathogen interactions. Little is currently known
      about the mechanisms underlying the effects exerted by foodborne microbes. We
      took advantage of C. elegans to evaluate the impact of foodborne microbiota on
      well characterized physiological features of the worms. Foodborne lactic acid
      bacteria (LAB) consortium was used to feed nematodes and its composition was
      evaluated by 16S rDNA analysis and strain typing before and after colonization of
      the nematode gut. Lactobacillus delbrueckii, L. fermentum, and Leuconostoc lactis
      were identified as the main species and shown to display different worm gut
      colonization capacities. LAB supplementation appeared to decrease nematode
      lifespan compared to the animals fed with the conventional Escherichia coli
      nutrient source or a probiotic bacterial strain. Reduced brood size was also
      observed in microbiota-fed nematodes. Moreover, massive accumulation of lipid
      droplets was revealed by BODIPY staining. Altered expression of nhr-49, pept-1,
      and tub-1 genes, associated with obesity phenotypes, was demonstrated by RT-qPCR.
      Since several pathways are evolutionarily conserved in C. elegans, our results
      highlight the nematode as a valuable model system to investigate the effects of a
      complex microbial consortium on host energy metabolism. 

PMID- 25961033
TI  - Bioactive natural products: facts, applications, and challenges.

PMID- 25961032
TI  - Activation of Sonic Hedgehog Leads to Survival Enhancement of Astrocytes via the
      GRP78-Dependent Pathway in Mice Infected with Angiostrongylus cantonensis.
AB  - Angiostrongylus cantonensis infection may cause elevation of ROS and antioxidants
      in the CSF of infected mice. Astrocytes may protect the surrounding neurons from
      oxidative stress-induced cell death by secreting Sonic hedgehog (Shh) via the PI3
      K/AKT/Bcl-2 pathway. This study was conducted to determine the role of the Shh
      signaling pathway in A. cantonensis-infected BABL/c mice by coculturing
      astrocytes with living fifth-stage larvae or soluble antigens. The Shh pathway
      was activated with corresponding increases in the level of the Shh. Glial
      fibrillary acidic protein (GFAP) and Shh were increased in astrocyte cocultured
      with living fifth-stage larvae or soluble antigens. The survival of astrocytes
      pretreated with Shh was significantly elevated in cocultures with the antigens
      but reduced by its inhibitor cyclopamine. The expression of GRP78 and Bcl-2 was
      significantly higher in astrocytes pretreated with recombinant Shh. These
      findings suggest that the expression of Shh may inhibit cell death by activating
      Bcl-2 through a GRP78-dependent pathway. 

PMID- 25961034
TI  - Molecular mechanism of muscle contraction: new perspectives and ideas.

PMID- 25961036
TI  - Familial Parkinson's disease/parkinsonism.

PMID- 25961037
TI  - The R21C Mutation in Cardiac Troponin I Imposes Differences in Contractile Force
      Generation between the Left and Right Ventricles of Knock-In Mice.
AB  - We investigated the effect of the hypertrophic cardiomyopathy-linked R21C
      (arginine to cysteine) mutation in human cardiac troponin I (cTnI) on the
      contractile properties and myofilament protein phosphorylation in papillary
      muscle preparations from left (LV) and right (RV) ventricles of homozygous
      R21C(+/+) knock-in mice. The maximal steady-state force was significantly reduced
      in skinned papillary muscle strips from the LV compared to RV, with the latter
      displaying the level of force observed in LV or RV from wild-type (WT) mice.
      There were no differences in the Ca(2+) sensitivity between the RV and LV of
      R21C(+/+) mice; however, the Ca(2+) sensitivity of force was higher in RV
      R21C(+/+) compared with RV-WT and lower in LV- R21C(+/+) compared with LV-WT. We
      also observed partial loss of Ca(2+) regulation at low [Ca(2+)]. In addition,
      R21C(+/+)-KI hearts showed no Ser23/24-cTnI phosphorylation compared to LV or RV
      of WT mice. However, phosphorylation of the myosin regulatory light chain (RLC)
      was significantly higher in the RV versus LV of R21C(+/+) mice and versus LV and
      RV of WT mice. The difference in RLC phosphorylation between the ventricles of
      R21C(+/+) mice likely contributes to observed differences in contractile force
      and the lower tension monitored in the LV of HCM mice. 

PMID- 25961038
TI  - What augmented physical activity and empowerment can bring to patients receiving
      total knee replacement: content, implementation, and comparative effectiveness of
      a new function-tailored care pathway in a routine care setting.
AB  - BACKGROUND: In the routine setting of the 20-bed orthopaedic ward of a regional
      hospital in Netherlands, we developed, implemented, and evaluated a new, function
      tailored perioperative care pathway for patients receiving total knee replacement
      (TKR), aimed at faster functional recovery by reduction of inactivity and
      stimulation of self-efficacy of the patients. METHODS: To assess effectiveness,
      we compared, using prospectively collected data from medical files, patient
      groups before (n = 127) and after (n = 108) introduction of the new care pathway
      with respect to time to recovery of physical functioning during hospitalisation
      (five milestones), length of hospital stay (LoS), referrals to an inpatient
      rehabilitation facility, and readmissions. Multivariable regression was used to
      adjust results for differences between the two groups in preoperatively assessed
      risk factors for delayed recovery. RESULTS: Comparison of patient groups before
      (n = 127) and after (n = 108) introduction of the tailored care pathway showed
      that the tailored rehabilitation pathway decreased the time to recovery of
      physical functioning (from 4.5 to 4.1 days, P < 0.05), the mean LoS (from 5.2
      days to 4.2 days, P < 0.01). CONCLUSION: We demonstrated that the introduction of
      a function-tailored care pathway shortens the hospital stay and accelerates the
      recovery of physical functioning.

PMID- 25961039
TI  - Identification of Novel Breast Cancer Subtype-Specific Biomarkers by Integrating
      Genomics Analysis of DNA Copy Number Aberrations and miRNA-mRNA Dual Expression
      Profiling.
AB  - Breast cancer is a heterogeneous disease with well-defined molecular subtypes.
      Currently, comparative genomic hybridization arrays (aCGH) techniques have been
      developed rapidly, and recent evidences in studies of breast cancer suggest that
      tumors within gene expression subtypes share similar DNA copy number aberrations
      (CNA) which can be used to further subdivide subtypes. Moreover, subtype-specific
      miRNA expression profiles are also proposed as novel signatures for breast cancer
      classification. The identification of mRNA or miRNA expression-based breast
      cancer subtypes is considered an instructive means of prognosis. Here, we
      conducted an integrated analysis based on copy number aberrations data and miRNA
      mRNA dual expression profiling data to identify breast cancer subtype-specific
      biomarkers. Interestingly, we found a group of genes residing in subtype-specific
      CNA regions that also display the corresponding changes in mRNAs levels and their
      target miRNAs' expression. Among them, the predicted direct correlation of BRCA1
      miR-143-miR-145 pairs was selected for experimental validation. The study results
      indicated that BRCA1 positively regulates miR-143-miR-145 expression and miR-143
      miR-145 can serve as promising novel biomarkers for breast cancer subtyping. In
      our integrated genomics analysis and experimental validation, a new frame to
      predict candidate biomarkers of breast cancer subtype is provided and offers
      assistance in order to understand the potential disease etiology of the breast
      cancer subtypes. 

PMID- 25961040
TI  - A Kinase Anchoring Protein 9 Is a Novel Myosin VI Binding Partner That Links
      Myosin VI with the PKA Pathway in Myogenic Cells.
AB  - Myosin VI (MVI) is a unique motor protein moving towards the minus end of actin
      filaments unlike other known myosins. Its important role has recently been
      postulated for striated muscle and myogenic cells. Since MVI functions through
      interactions of C-terminal globular tail (GT) domain with tissue specific
      partners, we performed a search for MVI partners in myoblasts and myotubes using
      affinity chromatography with GST-tagged MVI-GT domain as a bait. A kinase
      anchoring protein 9 (AKAP9), a regulator of PKA activity, was identified by means
      of mass spectrometry as a possible MVI interacting partner both in
      undifferentiated and differentiating myoblasts and in myotubes.
      Coimmunoprecipitation and proximity ligation assay confirmed that both proteins
      could interact. MVI and AKAP9 colocalized at Rab5 containing early endosomes.
      Similarly to MVI, the amount of AKAP9 decreased during myoblast differentiation.
      However, in MVI-depleted cells, both cAMP and PKA levels were increased and a
      change in the MVI motor-dependent AKAP9 distribution was observed. Moreover, we
      found that PKA phosphorylated MVI-GT domain, thus implying functional relevance
      of MVI-AKAP9 interaction. We postulate that this novel interaction linking MVI
      with the PKA pathway could be important for targeting AKAP9-PKA complex within
      cells and/or providing PKA to phosphorylate MVI tail domain. 

PMID- 25961035
TI  - The sarcomeric M-region: a molecular command center for diverse cellular
      processes.
AB  - The sarcomeric M-region anchors thick filaments and withstands the mechanical
      stress of contractions by deformation, thus enabling distribution of
      physiological forces along the length of thick filaments. While the role of the M
      region in supporting myofibrillar structure and contractility is well
      established, its role in mediating additional cellular processes has only
      recently started to emerge. As such, M-region is the hub of key protein players
      contributing to cytoskeletal remodeling, signal transduction, mechanosensing,
      metabolism, and proteasomal degradation. Mutations in genes encoding M-region
      related proteins lead to development of severe and lethal cardiac and skeletal
      myopathies affecting mankind. Herein, we describe the main cellular processes
      taking place at the M-region, other than thick filament assembly, and discuss
      human myopathies associated with mutant or truncated M-region proteins. 

PMID- 25961041
TI  - Correlation between the Quality of Attention and Cognitive Competence with Motor
      Action in Stroke Patients.
AB  - It is considered that cognitive function and attention could affect walking,
      motion control, and proper conduct during the walk. To determine whether there is
      a difference in the quality of attention and cognitive ability in stroke patients
      and patients without neurological damage of similar age and education and to
      determine whether the connection of attention and cognition affects motor skills,
      the sample consisted of 50 stroke patients tested with hemiparesis, involved in
      the process of rehabilitation, and 50 persons, randomly chosen, without
      neurological damage. The survey used the following tests: Trail Making (TMT A B)
      test for assessing the flexibility of attention; Mini-Mental State Examination
      (MMSE) for cognitive status; Functional Ambulation Category (FAC) test to assess
      the functional status and parameters of walk: speed, frequency, and length of
      stride; STEP test for assessing the precision of movement and balance. With
      stroke patients, relationship between age and performance on the MMSE test was
      marginally significant. The ratio of performance to TMT A B test and years does
      not indicate statistical significance, while statistical significance between the
      MMSE test performance and education exists. In stroke patients, performance on
      MMSE test is correlated with the frequency and length of stride walk. The quality
      of cognitive function and attention is associated with motor skills but differs
      in stroke patients and people without neurological damage of similar age. The
      significance of this correlation can supplement research in neurorehabilitation,
      improve the quality of medical rehabilitation, and contribute to efficient
      recovery of these patients. 

PMID- 25961042
TI  - A Novel Operative Procedure for Pelvic Organ Prolapse Utilizing a MRI-Visible
      Mesh Implant: Safety and Outcome of Modified Laparoscopic Bilateral Sacropexy.
AB  - INTRODUCTION: Sacropexy is a generally applied treatment of prolapse, yet there
      are known possible complications of it. An essential need exists for better
      alloplastic materials. METHODS: Between April 2013 and June 2014, we performed a
      modified laparoscopic bilateral sacropexy (MLBS) in 10 patients using a MRI
      visible PVDF mesh implant. Selected patients had prolapse POP-Q stages II-III and
      concomitant OAB. We studied surgery-related morbidity, anatomical and functional
      outcome, and mesh-visibility in MRI. Mean follow-up was 7.4 months. RESULTS:
      Concomitant colporrhaphy was conducted in 1/10 patients. Anatomical success was
      defined as POP-Q stage 0-I. Apical success rate was 100% and remained stable. A
      recurrent cystocele was seen in 1/10 patients during follow-up without need for
      intervention. Out of 6 (6/10) patients with preoperative SUI, 5/6 were healed and
      1/6 persisted. De-novo SUI was seen in 1/10 patients. Complications requiring a
      relaparoscopy were seen in 2/10 patients. 8/10 patients with OAB were relieved
      postoperatively. The first in-human magnetic resonance visualization of a
      prolapse mesh implant was performed and showed good quality of visualization.
      CONCLUSION: MLBS is a feasible and safe procedure with favorable anatomical and
      functional outcome and good concomitant healing rates of SUI and OAB. Prospective
      data and larger samples are required.

PMID- 25961043
TI  - Effect of Electrode Shape on Impedance of Single HeLa Cell: A COMSOL Simulation.
AB  - In disease prophylaxis, single cell inspection provides more detailed data
      compared to conventional examinations. At the individual cell level, the
      electrical properties of the cell are helpful for understanding the effects of
      cellular behavior. The electric field distribution affects the results of single
      cell impedance measurements whereas the electrode geometry affects the electric
      field distributions. Therefore, this study obtained numerical solutions by using
      the COMSOL multiphysics package to perform FEM simulations of the effects of
      electrode geometry on microfluidic devices. An equivalent circuit model
      incorporating the PBS solution, a pair of electrodes, and a cell is used to
      obtain the impedance of a single HeLa cell. Simulations indicated that the circle
      and parallel electrodes provide higher electric field strength compared to cross
      and standard electrodes at the same operating voltage. Additionally, increasing
      the operating voltage reduces the impedance magnitude of a single HeLa cell in
      all electrode shapes. Decreasing impedance magnitude of the single HeLa cell
      increases measurement sensitivity, but higher operational voltage will damage
      single HeLa cell. 

PMID- 25961045
TI  - A Practical and Scalable Tool to Find Overlaps between Sequences.
AB  - The evolution of the next generation sequencing technology increases the demand
      for efficient solutions, in terms of space and time, for several bioinformatics
      problems. This paper presents a practical and easy-to-implement solution for one
      of these problems, namely, the all-pairs suffix-prefix problem, using a compact
      prefix tree. The paper demonstrates an efficient construction of this time
      efficient and space-economical tree data structure. The paper presents techniques
      for parallel implementations of the proposed solution. Experimental evaluation
      indicates superior results in terms of space and time over existing solutions.
      Results also show that the proposed technique is highly scalable in a parallel
      execution environment. 

PMID- 25961044
TI  - Improving the Understanding of Pathogenesis of Human Papillomavirus 16 via
      Mapping Protein-Protein Interaction Network.
AB  - The human papillomavirus 16 (HPV16) has high risk to lead various cancers and
      afflictions, especially, the cervical cancer. Therefore, investigating the
      pathogenesis of HPV16 is very important for public health. Protein-protein
      interaction (PPI) network between HPV16 and human was used as a measure to
      improve our understanding of its pathogenesis. By adopting sequence and
      topological features, a support vector machine (SVM) model was built to predict
      new interactions between HPV16 and human proteins. All interactions were
      comprehensively investigated and analyzed. The analysis indicated that HPV16
      enlarged its scope of influence by interacting with human proteins as much as
      possible. These interactions alter a broad array of cell cycle progression.
      Furthermore, not only was HPV16 highly prone to interact with hub proteins and
      bottleneck proteins, but also it could effectively affect a breadth of signaling
      pathways. In addition, we found that the HPV16 evolved into high carcinogenicity
      on the condition that its own reproduction had been ensured. Meanwhile, this work
      will contribute to providing potential new targets for antiviral therapeutics and
      help experimental research in the future. 

PMID- 25961046
TI  - Seroprevalence of Toxoplasma gondii Infection in Patients of Intensive Care Unit
      in China: A Hospital Based Study.
AB  - The objective of this study was to estimate the seroprevalence of Toxoplasma
      gondii infection in 394 patients of intensive care unit (ICU) in a hospital
      between April 2010 and March 2012 and analyze the association between T. gondii
      infection and ICU patients according to the species of disease. Toxoplasma
      serology was evaluated by ELISA method using a commercially available kit. Data
      of patients were obtained from the patients, informants, and medical examination
      records. Seventy-four (18.78%) of 394 patients were positive for anti-T. gondii
      IgG antibodies demonstrating latent infection. Of these, the highest T. gondii
      seroprevalence was found in the age group of 31-45 years (27.45%), and the lowest
      was found in the age group of <30 years (12.5%). In addition, females (21.6%) had
      a higher seroprevalence than males (18.36%). With respect to the species of
      disease, the patients with kidney diseases (57.14%), lung diseases (27.84%), and
      brain diseases (24%) had high T. gondii seroprevalence. The present study
      represents the first survey of T. gondii seroprevalence in ICU patients in China,
      revealing an 18.78% seropositivity. Considering the particularities of ICU
      patients, molecular identification, genetic characterization, and diagnosis of T.
      gondii should be considered in future study. 

PMID- 25961047
TI  - African flora has the potential to fight multidrug resistance of cancer.
AB  - BACKGROUND: Continuous efforts from scientists of diverse fields are necessary
      not only to better understand the mechanism by which multidrug-resistant (MDR)
      cancer cells occur, but also to boost the discovery of new cytotoxic compounds to
      fight MDR phenotypes. OBJECTIVES: The present review reports on the contribution
      of African flora in the discovery of potential cytotoxic phytochemicals against
      MDR cancer cells. Methodology. Scientific databases such as PubMed,
      ScienceDirect, Scopus, Google Scholar, and Web of Knowledge were used to retrieve
      publications related to African plants, isolated compounds, and drug resistant
      cancer cells. The data were analyzed to highlight cytotoxicity and the modes of
      actions of extracts and compounds of the most prominent African plants. Also,
      thresholds and cutoff points for the cytotoxicity and modes of action of
      phytochemicals have been provided. RESULTS: Most published data related to the
      antiproliferative potential of African medicinal plants were from Cameroon,
      Egypt, Nigeria, or Madagascar. The cytotoxicity of phenolic compounds isolated in
      African plants was generally much better documented than that of terpenoids and
      alkaloids. CONCLUSION: African flora represents an enormous resource for novel
      cytotoxic compounds. To unravel the full potential, efforts should be
      strengthened throughout the continent, to meet the challenge of a successful
      fight against MDR cancers.

PMID- 25961048
TI  - Detection of tropical fungi in formalin-fixed, paraffin-embedded tissue: still an
      indication for microscopy in times of sequence-based diagnosis?
AB  - INTRODUCTION: The aim of the study was the evaluation of panfungal PCR protocols
      with subsequent sequence analysis for the diagnostic identification of invasive
      mycoses in formalin-fixed, paraffin-embedded tissue samples with rare tropical
      mycoses. MATERIALS AND METHODS: Five different previously described panfungal
      PCR/sequencing protocols targeting 18S and 28S ribosomal RNA gene fragments as
      well as internal transcribed spacer 1 and 2 fragments were evaluated with a
      collection of 17 formalin-fixed, paraffin-embedded tissue samples of patients
      with rare and/or tropical invasive mycoses, comprising chromoblastomycosis,
      coccidioidomycosis, cryptococcosis, histoplasmosis, mucormycosis,
      mycetoma/maduromycosis, and rhinosporidiosis, in a proof-of-principle analysis.
      RESULTS: The primers of the panfungal PCRs readily and predominantly reacted with
      contaminating environmental fungi that had deposited on the paraffin blocks.
      Altogether three sequence results of histoplasmosis and mycetoma samples that
      matched the histological assessment were associated with sample age <10 years and
      virtually without PCR inhibition. CONCLUSIONS: The high risk of amplifying
      environmental contaminants severely reduces the usefulness of the assessed
      panfungal PCR/sequencing protocols for the identification of rare and/or tropical
      mycoses in stored formalin-fixed, paraffin-embedded tissues. Histological
      assessment remains valuable for such indications if cultural differentiation is
      impossible from inactivated sample material.

PMID- 25961049
TI  - Comparative Orbital Volumes between a Single Incisional Approach and a Double
      Incisional Approach in Patients with Combined Blowout Fracture.
AB  - PURPOSE: Blowout fracture characterized by concurrent floor and medial wall
      fractures is a rare entity. We compared surgical outcomes between a single
      approach and a double approach in patients with orbital fracture by measuring the
      postoperative orbital volume. METHODS: We confirmed that 21 (8.5%) of a total of
      246 patients with orbital fractures had fractures of the medial wall and floor
      through a retrospective chart review. Of these, 10 patients underwent the single
      approach and the remaining 11 patients had the double approach. We performed a
      statistical analysis of changes between the preoperative and postoperative
      orbital volumes at a 6-month follow-up. RESULTS: Compared with the contralateral,
      nonaffected side, the orbital volume was 115.3 (+/-6.09)% preoperatively and
      106.5 (+/-6.15)% postoperatively in the single approach group and 118.2 (+/
      11.16)% preoperatively and 108.6 (+/-13.96)% postoperatively in the double
      approach. These results indicated that there was a significant difference between
      the preoperative and postoperative orbital volumes in each group (P < 0.05).
      However there was no significant difference between the single approach and the
      double approach (P > 0.05). CONCLUSIONS: Our results showed that there were no
      significant differences in surgical outcomes between the two modalities. The
      treatment modality may be selected based on the surgeons' preference, as well as
      the fracture type.

PMID- 25961050
TI  - Plasma Lactate Levels Increase during Hyperinsulinemic Euglycemic Clamp and Oral
      Glucose Tolerance Test.
AB  - Insulin resistance, which plays a central role in the pathogenesis of type 2
      diabetes (T2D), is an early indicator that heralds the occurrence of T2D. It is
      imperative to understand the metabolic changes that occur at the cellular level
      in the early stages of insulin resistance. The objective of this study was to
      determine the pattern of circulating lactate levels during oral glucose tolerance
      test (OGTT) and hyperinsulinemic euglycemic clamp (HIEC) study in normal
      nondiabetic subjects. Lactate and glycerol were determined every 30 minutes
      during OGTT and HIEC on 22 participants. Lactate progressively increased
      throughout the HIEC study period (P < 0.001). Participants with BMI < 30 had
      significantly higher mean M-values compared to those with BMI >= 30 at baseline
      (P < 0.05). This trend also continued throughout the OGTT. In addition, those
      with impaired glucose tolerance test (IGT) had significantly higher mean lactate
      levels compared to those with normal glucose tolerance (P < 0.001). In
      conclusion, we found that lactate increased during HIEC study, which is a state
      of hyperinsulinemia similar to the metabolic milieu seen during the early stages
      in the development of T2D. 

PMID- 25961051
TI  - Effectiveness of a nurse-managed protocol to prevent hypoglycemia in hospitalized
      patients with diabetes.
AB  - BACKGROUND: Hypoglycemia due to inadequate carbohydrate intake is a frequent
      complication of insulin treatment of diabetic in-patients. Objective. To assess
      the effectiveness of a nurse-managed protocol to prevent hypoglycemia during
      subcutaneous insulin treatment. DESIGN: Prospective pre-post-intervention study.
      METHODS: In 350 consecutive diabetic in-patients the incidence of hypoglycemia
      (blood glucose < 70 mg/dL) during subcutaneous insulin treatment was assessed
      before (phase A) and after (phase B) the protocol was adopted to permit (1) the
      patient to opt for substitutive food to integrate incomplete carbohydrate intake
      in the meal; (2) in case of lack of appetite or repeatedly partial intake of the
      planned food, prandial insulin administered at the end of the meal to be related
      to the actual amount of carbohydrates eaten; (3) intravenous infusion of glucose
      during prolonged fasting. RESULTS: Eighty-four patients in phase A and 266 in
      phase B received subcutaneous insulin for median periods of, respectively, 7 (Q1
      Q3 6-12) and 6 days (Q1-Q3 4-9). Hypoglycemic events declined significantly from
      0.34 +/- 0.33 per day in phase A to 0.19 +/- 0.30 in phase B (P > 0.001).
      CONCLUSIONS: A nurse-managed protocol focusing on carbohydrate intake reduced the
      incidence of hypoglycemia in patients with diabetes receiving subcutaneous
      insulin in hospital.

PMID- 25961052
TI  - Characterization of the Prediabetic State in a Novel Rat Model of Type 2
      Diabetes, the ZFDM Rat.
AB  - We recently established a novel animal model of obese type 2 diabetes (T2D), the
      Zucker fatty diabetes mellitus (ZFDM) rat strain harboring the fatty mutation
      (fa) in the leptin receptor gene. Here we performed a phenotypic characterization
      of the strain, focusing mainly on the prediabetic state. At 6-8 weeks of age,
      fa/fa male rats exhibited mild glucose intolerance and severe insulin resistance.
      Although basal insulin secretion was remarkably high in the isolated pancreatic
      islets, the responses to both glucose stimulation and the incretin GLP-1 were
      retained. At 10-12 weeks of age, fa/fa male rats exhibited marked glucose
      intolerance as well as severe insulin resistance similar to that at the earlier
      age. In the pancreatic islets, the insulin secretory response to glucose
      stimulation was maintained but the response to the incretin was diminished. In
      nondiabetic Zucker fatty (ZF) rats, the insulin secretory responses to both
      glucose stimulation and the incretin in the pancreatic islets were similar to
      those of ZFDM rats. As islet architecture was destroyed with age in ZFDM rats, a
      combination of severe insulin resistance, diminished insulin secretory response
      to incretin, and intrinsic fragility of the islets may cause the development of
      T2D in this strain. 

PMID- 25961053
TI  - Characterization of the ZDSD Rat: A Translational Model for the Study of
      Metabolic Syndrome and Type 2 Diabetes.
AB  - Metabolic syndrome and T2D produce significant health and economic issues. Many
      available animal models have monogenic leptin pathway mutations that are absent
      in the human population. Development of the ZDSD rat model was undertaken to
      produce a model that expresses polygenic obesity and diabetes with an intact
      leptin pathway. A lean ZDF rat with the propensity for beta-cell failure was
      crossed with a polygenetically obese Crl:CD (SD) rat. Offspring were selectively
      inbred for obesity and diabetes for >30 generations. In the current study, ZDSD
      rats were followed for 6 months; routine clinical metabolic endpoints were
      included throughout the study. In the prediabetic metabolic syndrome phase, ZDSD
      rats exhibited obesity with increased body fat, hyperglycemia, insulin
      resistance, dyslipidemia, glucose intolerance, and elevated HbA1c. As disease
      progressed to overt diabetes, ZDSD rats demonstrated elevated glucose levels,
      abnormal oral glucose tolerance, increases in HbA1c levels, reductions in body
      weight, increased insulin resistance with decreasing insulin levels, and
      dyslipidemia. The ZDSD rat develops prediabetic metabolic syndrome and T2D in a
      manner that mirrors the development of metabolic syndrome and T2D in humans. ZDSD
      rats will provide a novel, translational animal model for the study of human
      metabolic diseases and for the development of new therapies. 

PMID- 25961054
TI  - The Association between Serum Cytokines and Damage to Large and Small Nerve
      Fibers in Diabetic Peripheral Neuropathy.
AB  - Diabetic peripheral neuropathy (DPN) is a frequent complication of type 2
      diabetes mellitus (DM) and may involve small and large peripheral nerve fibers.
      Recent evidence suggests a role of cytokines in DPN. The paper is aimed at
      exploring whether the serum concentration of cytokines is associated with small
      and large nerve fiber function and with neuropathic pain (NP). We recruited a
      group of 32 type 2 DM patients who underwent serum cytokines (TNF-alpha, IL-2, IL
      4, IL-6, and IL-10) dosage as well as electrodiagnostic and quantitative sensory
      testing (QST) assessment to explore damage to large and small nerve fibers.
      Raised serum levels of IL-6 and IL-10 correlated with markers of large nerve
      fiber sensory and motor axonal damage. Raised IL-10 serum level was associated
      with signs of motor nerve demyelination. No differences were found in pain
      characteristics and electrodiagnostic and QST markers of small nerve fiber
      function in relation to cytokines serum levels. IL-6 and IL-10 serum levels were
      associated with large nerve fiber damage but not to small fibers function or NP.
      IL-6 and IL-10 cytokines might play a role in the pathogenesis of nerve fiber
      damage or represent a compensatory or neuroprotective mechanism. 

PMID- 25961055
TI  - Beneficial effects of omega-3 polyunsaturated Fatty acids in gestational
      diabetes: consequences in macrosomia and adulthood obesity.
AB  - Omega-3 polyunsaturated fatty acids (PUFAs) are increasingly being used to
      prevent cardiovascular diseases, including diabetes and obesity. In this paper,
      we report data on the observed effects of omega-3 PUFA on major metabolic
      disorders and immune system disruption during gestational diabetes and their
      consequences on macrosomia. While controversies still exist about omega-3 PUFA
      effects on antioxidant status regarding the level of omega-3 PUFA in diet
      supplementation, their lipid-lowering effects are unanimously recognized by
      researchers. Animal studies have shown that omega-3 PUFA contributes to the
      maintenance of the immune defense system by promoting the differentiation of T
      helper (Th) cell to a Th2 phenotype in diabetic pregnancy and by shifting the
      Th1/Th2 ratio from a deleterious proinflammatory Th1 phenotype to a protective
      anti-inflammatory Th2 phenotype in macrosomia and in adulthood obesity that
      results from macrosomia at birth. Based on the available evidence, international
      nutritional and food agencies recommend administration of omega-3 PUFA as
      triglyceride-lowering agents, for the prevention of cardiovascular disease risk
      and during human pregnancy and lactation. Furthermore, studies targeting humans
      are still required to explore application of the fatty acids as supplement in the
      management of gestational diabetes and inflammatory and immune diseases. 

PMID- 25961056
TI  - Immunological hypoglycemia associated with insulin antibodies induced by
      exogenous insulin in 11 Chinese patients with diabetes.
AB  - AIMS: To investigate the characteristics of immunological hypoglycemia associated
      with insulin antibodies (IAbs) induced by exogenous insulin in Chinese patients
      with diabetes. METHODS: The clinical data of patients with immunological
      hypoglycemia due to IAbs were retrospectively analyzed by screening patients with
      diabetes discharged from West China Hospital from 2007 to 2013. RESULTS: A total
      of 11 patients (eight men and three women) were identified. Insulin-C-peptide
      separation was found in all patients via insulin and C-peptide release test.
      Previous insulin use was ceased after admission and was switched to oral
      hypoglycemic agents (OHAs) (8/11), lifestyle modification only (2/11), or regular
      human insulin (1/11). Hypoglycemia was ameliorated after a median of 20 days
      (interquartile range [IQR], 11-40), while IAbs turned negative after a median of
      17 months (IQR, 4-19), and serum immunoreactive insulin (IRI) levels dropped
      substantially after a median of 22 months (IQR, 9-32) in these cases.
      CONCLUSIONS: In insulin-treated patients with unexpected and refractory
      hypoglycemia even after insulin therapy was gradually reduced or even withdrawn,
      IAbs induced by exogenous insulin should be considered, and insulin withdrawal
      might be promptly needed. The course of immunological hypoglycemia was benign and
      self-limited.

PMID- 25961057
TI  - Glucocorticoid-induced tumour necrosis factor receptor-related protein: a key
      marker of functional regulatory T cells.
AB  - Glucocorticoid-induced tumour necrosis factor receptor-related protein (GITR,
      TNFRSF18, and CD357) is expressed at high levels in activated T cells and
      regulatory T cells (Tregs). In this review, we present data from mouse and human
      studies suggesting that GITR is a crucial player in the differentiation of thymic
      Tregs (tTregs), and expansion of both tTregs and peripheral Tregs (pTregs). The
      role of GITR in Treg expansion is confirmed by the association of GITR expression
      with markers of memory T cells. In this context, it is not surprising that GITR
      appears to be a marker of active Tregs, as suggested by the association of GITR
      expression with other markers of Treg activation or cytokines with suppressive
      activity (e.g., IL-10 and TGF-beta), the presence of GITR(+) cells in tissues
      where Tregs are active (e.g., solid tumours), or functional studies on Tregs.
      Furthermore, some Treg subsets including Tr1 cells express either low or no
      classical Treg markers (e.g., FoxP3 and CD25) and do express GITR. Therefore,
      when evaluating changes in the number of Tregs in human diseases, GITR expression
      must be evaluated. Moreover, GITR should be considered as a marker for isolating
      Tregs. 

PMID- 25961059
TI  - Immunoregulation by mesenchymal stem cells: biological aspects and clinical
      applications.
AB  - Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiation
      into mesenchymal lineages and that can be isolated from various tissues and
      easily cultivated in vitro. Currently, MSCs are of considerable interest because
      of the biological characteristics that confer high potential applicability in the
      clinical treatment of many diseases. Specifically, because of their high
      immunoregulatory capacity, MSCs are used as tools in cellular therapies for
      clinical protocols involving immune system alterations. In this review, we
      discuss the current knowledge about the capacity of MSCs for the immunoregulation
      of immunocompetent cells and emphasize the effects of MSCs on T cells, principal
      effectors of the immune response, and the immunosuppressive effects mediated by
      the secretion of soluble factors and membrane molecules. We also describe the
      mechanisms of MSC immunoregulatory modulation and the participation of MSCs as
      immune response regulators in several autoimmune diseases, and we emphasize the
      clinical application in graft versus host disease (GVHD). 

PMID- 25961058
TI  - Immunomodulatory effects mediated by serotonin.
AB  - Serotonin (5-HT) induces concentration-dependent metabolic effects in diverse
      cell types, including neurons, entherochromaffin cells, adipocytes, pancreatic
      beta-cells, fibroblasts, smooth muscle cells, epithelial cells, and leukocytes.
      Three classes of genes regulating 5-HT function are constitutively expressed or
      induced in these cells: (a) membrane proteins that regulate the response to 5-HT,
      such as SERT, 5HTR-GPCR, and the 5HT3-ion channels; (b) downstream signaling
      transduction proteins; and (c) enzymes controlling 5-HT metabolism, such as IDO
      and MAO, which can generate biologically active catabolites, including melatonin,
      kynurenines, and kynurenamines. This review covers the clinical and experimental
      mechanisms involved in 5-HT-induced immunomodulation. These mechanisms are cell
      specific and depend on the expression of serotonergic components in immune cells.
      Consequently, 5-HT can modulate several immunological events, such as chemotaxis,
      leukocyte activation, proliferation, cytokine secretion, anergy, and apoptosis.
      The effects of 5-HT on immune cells may be relevant in the clinical outcome of
      pathologies with an inflammatory component. Major depression, fibromyalgia,
      Alzheimer disease, psoriasis, arthritis, allergies, and asthma are all associated
      with changes in the serotonergic system associated with leukocytes. Thus,
      pharmacological regulation of the serotonergic system may modulate immune
      function and provide therapeutic alternatives for these diseases. 

PMID- 25961060
TI  - Immunomodulation and anti-inflammatory effects of garlic compounds.
AB  - The benefits of garlic to health have been proclaimed for centuries; however,
      only recently have Allium sativum and its derivatives been proposed as promising
      candidates for maintaining the homeostasis of the immune system. The complex
      biochemistry of garlic makes it possible for variations in processing to yield
      different preparations with differences in final composition and compound
      proportion. In this review, we assess the most recent experimental results, which
      indicate that garlic appears to enhance the functioning of the immune system by
      stimulating certain cell types, such as macrophages, lymphocytes, natural killer
      (NK) cells, dendritic cells, and eosinophils, by mechanisms including modulation
      of cytokine secretion, immunoglobulin production, phagocytosis, and macrophage
      activation. Finally, because immune dysfunction plays an important role in the
      development and progress of several diseases, we critically examined
      immunoregulation by garlic extracts and compounds isolated, which can contribute
      to the treatment and prevention of pathologies such as obesity, metabolic
      syndrome, cardiovascular disorders, gastric ulcer, and even cancer. We concluded
      that A. sativum modulates cytokine secretion and that such modulation may provide
      a mechanism of action for many of their therapeutic effects. 

PMID- 25961062
TI  - IL-10 and ARG-1 concentrations in bone marrow and peripheral blood of metastatic
      neuroblastoma patients do not associate with clinical outcome.
AB  - The expression of the immunosuppressive molecules IL-10 and arginase 1 (ARG-1),
      and of FOXP3 and CD163, as markers of regulatory T cells (Treg) and macrophages,
      respectively, was evaluated in bone marrow (BM) and peripheral blood (PB) samples
      collected at diagnosis from patients with metastatic neuroblastoma (NB). IL-10
      and ARG-1 plasma concentrations were measured and the association of each
      parameter with patients' outcome was tested. The percentages of immunosuppressive
      Treg and type-1 regulatory (Tr1) cells were also determined. In both BM and PB
      samples, IL-10 mRNA expression was higher in metastatic NB patients than in
      controls. IL-10 plasma concentration was higher in patients with NB regardless of
      stage. Neither IL-10 expression nor IL-10 plasma concentration significantly
      associated with patient survival. In PB samples from metastatic NB patients, ARG
      1 and CD163 expression was higher than in controls but their expression did not
      associate with survival. Moreover, ARG-1 plasma concentration was lower than in
      controls, and no association with patient outcome was found. Finally, in
      metastatic NB patients, the percentage of circulating Treg was higher than in
      controls, whereas that of Tr1 cells was lower. In conclusion, although IL-10
      concentration and Treg percentage were increased, their contribution to the
      natural history of metastatic NB appears uncertain. 

PMID- 25961061
TI  - IL-21: a pleiotropic cytokine with potential applications in oncology.
AB  - Interleukin- (IL-) 21 is a pleiotropic cytokine that regulates the activity of
      both innate and specific immunity. Indeed, it costimulates T and natural killer
      (NK) cell proliferation and function and regulates B cell survival and
      differentiation and the function of dendritic cells. In addition, IL-21 exerts
      divergent effects on different lymphoid cell leukemia and lymphomas, as it may
      support cell proliferation or on the contrary induce growth arrest or apoptosis
      of the neoplastic lymphoid cells. Several preclinical studies showed that IL-21
      has antitumor activity in different tumor models, through mechanism involving the
      activation of NK and T or B cell responses. Moreover, IL-21's antitumor activity
      can be potentiated by its combination with other immune-enhancing molecules,
      monoclonal antibodies recognizing tumor antigens, chemotherapy, or molecular
      targeted agents. Clinical phase I-II studies of IL-21 in cancer patients showed
      immune stimulatory properties, acceptable toxicity profile, and antitumor effects
      in a fraction of patients. In view of its tolerability, IL-21 is also suitable
      for combinational therapeutic regimens with other agents. This review will
      summarize the biological functions of IL-21, and address its role in lymphoid
      malignancies and preclinical and clinical studies of cancer immunotherapy. 

PMID- 25961063
TI  - Uptake of CCR7 by KIR2DS4+ NK cells is induced upon recognition of certain HLA-C
      alleles.
AB  - The KIR2DS4 receptor is the oldest KIR2DS expressed by human NK lymphocytes. The
      specificity of recognition of this receptor for various HLA class I alleles has
      been demonstrated; however it remains poorly understood whether these
      interactions may result in the activation of some specific functions in NK cells.
      Here, we examined the functional outcome of the KIR2DS4/HLA class I interaction
      by the use of an alternative functional system based on the ability of KIR2DS4 to
      regulate the mechanism of trogocytosis by NK cells. We demonstrate that KIR2DS4
      can induce the uptake of CCR7 by KIR2DS4(+) NKG2A(+) NK cell clones after
      interacting with CCR7(+) target cells expressing HLA-Cw4 and HLA-Cw6 alleles.
      However this interaction is not always sufficient to override the inhibition
      generated by NKG2A expressed on the same NK cells. The recognition of HLA-Cw4 was
      confirmed by experiments of cytotoxicity against HLA-C-transfected cells. We also
      show that, different from resting NK cells, the acquisition of CCR7 in response
      to IL-18 cannot occur in IL2-activated NK cells because of a marked
      downregulation in their IL-18Ralpha expression. As a consequence trogocytosis
      represents the major mechanism by which KIR2DS4(+) activated NK cells acquire the
      expression of this chemokine receptor. 

PMID- 25961065
TI  - Transporting Young Passengers While Impaired: The State of the Law.
AB  - OBJECTIVE: This study sought to expand public health knowledge about the legal
      and policy aspects of DUI-child endangerment laws, and analyze the extent to
      which jurisdictions give priority to the protection of children. METHODS: We
      performed original legal research to locate and code driving-under-the-influence
      (DUI)-child endangerment laws across the 50 states and the District of Columbia,
      enabling us to compile a baseline legal dataset. RESULTS: Only 42 of the 51
      jurisdictions address DUI-child endangerment in their statutes. Of the
      jurisdictions that do, the most comprehensive policies and those most protective
      of the safety of child passengers are not available in many jurisdictions.
      However, we found no significant relationship between the strength
      (comprehensiveness) of DUI-child endangerment laws and the proportion of child
      fatalities by a driver with a BAC >=.08. CONCLUSIONS: Additional work needs to be
      done to improve state laws on DUI-child endangerment. The 9 jurisdictions that do
      not directly address this public health harm can enact laws to do so, and the 42
      jurisdictions that already have laws can enhance their approaches to prioritize
      the protection of children. We suggest that future research include a close
      examination of the impact of DUI-child endangerment laws.

PMID- 25961064
TI  - Downmodulation of vaccine-induced immunity and protection against the
      intracellular bacterium Francisella tularensis by the inhibitory receptor
      FcgammaRIIB.
AB  - Fc gamma receptor IIB (FcgammaRIIB) is the only Fc gamma receptor (FcgammaR)
      which negatively regulates the immune response, when engaged by antigen- (Ag-)
      antibody (Ab) complexes. Thus, the generation of Ag-specific IgG in response to
      infection or immunization has the potential to downmodulate immune protection
      against infection. Therefore, we sought to determine the impact of FcgammaRIIB on
      immune protection against Francisella tularensis (Ft), a Category A biothreat
      agent. We utilized inactivated Ft (iFt) as an immunogen. Naive and iFt-immunized
      FcgammaRIIB knockout (KO) or wildtype (WT) mice were challenged with Ft-live
      vaccine strain (LVS). While no significant difference in survival between naive
      FcgammaRIIB KO versus WT mice was observed, iFt-immunized FcgammaRIIB KO mice
      were significantly better protected than iFt-immunized WT mice. Ft-specific IgA
      in serum and bronchial alveolar lavage, as well as IFN-gamma, IL-10, and TNF
      alpha production by splenocytes harvested from iFt-immunized FcgammaRIIB KO, were
      also significantly elevated. In addition, iFt-immunized FcgammaRIIB KO mice
      exhibited a reduction in proinflammatory cytokine levels in vivo at 5 days after
      challenge, which correlates with increased survival following Ft-LVS challenge in
      published studies. Thus, these studies demonstrate for the first time the ability
      of FcgammaRIIB to regulate vaccine-induced IgA production and downmodulate
      immunity and protection. The immune mechanisms behind the above observations and
      their potential impact on vaccine development are discussed. 

PMID- 25961066
TI  - Demonstrating Patterns in the Views Of Stakeholders Regarding Ethically-Salient
      Issues in Clinical Research: A Novel Use of Graphical Models in Empirical Ethics
      Inquiry.
AB  - BACKGROUND: Empirical ethics inquiry works from the notion that stakeholder
      perspectives are necessary for gauging the ethical acceptability of human studies
      and assuring that research aligns with societal expectations. Although common,
      studies involving different populations often entail comparisons of trends that
      problematize the interpretation of results. Using graphical model selection - a
      technique aimed at transcending limitations of conventional methods - this report
      presents data on the ethics of clinical research with two objectives: (1) to
      display the patterns of views held by ill and healthy individuals in clinical
      research as a test of the study's original hypothesis and (2) to introduce
      graphical model selection as a key analytic tool for ethics research. METHODS: In
      this IRB-approved, NIH-funded project, data were collected from 60 mentally ill
      and 43 physically ill clinical research protocol volunteers, 47 healthy protocol
      consented participants, and 29 healthy individuals without research protocol
      experience. Respondents were queried on the ethical acceptability of research
      involving people with mental and physical illness (i.e., cancer, HIV, depression,
      schizophrenia, and post-traumatic stress disorder) and non-illness related
      sources of vulnerability (e.g., age, class, gender, ethnicity). Using a
      statistical algorithm, we selected graphical models to display interrelationships
      among responses to questions. RESULTS: Both mentally and physically ill protocol
      volunteers revealed a high degree of connectivity among ethically-salient
      perspectives. Healthy participants, irrespective of research protocol experience,
      revealed patterns of views that were not highly connected. CONCLUSION: Between
      ill and healthy protocol participants, the pattern of views is vastly different.
      Experience with illness was tied to dense connectivity, whereas healthy
      individuals expressed views with sparse connections. In offering a nuanced
      perspective on the interrelation of ethically relevant responses, graphical model
      selection has the potential to bring new insights to the field of ethics.

PMID- 25961067
TI  - Effects of Brain-Derived IL-2 Deficiency and the Development of Autoimmunity on
      Spatial Learning and Fear Conditioning.
AB  - Interleukin-2 (IL-2) has been implicated in neurological disorders including
      multiple sclerosis and Alzheimer's disease. Peripheral IL-2 deficiency in gene
      deleted mice results in T cell mediated autoimmunity that begins to develop
      slowly after weaning and progressively increases through adulthood. Loss of brain
      derived IL-2 results in neurobiological and behavioral abnormalities, and may
      contribute to the development of CNS autoimmunity by modifying the
      neuroimmunological milieu of the brain. We have shown previously that IL-2
      knockout (KO) mice have altered learning acquisition in the Morris water-maze.
      Hypothesizing that the learning acquisition deficits in IL-2KO would be
      associated largely with the loss of brain-derived IL-2, the present study sought
      to determine if these cognitive alterations are due to the loss the IL-2 gene in
      the brain and/or autoimmunity resulting from loss of the gene in the peripheral
      immune system. We found that SCID congenic mice (mice free of IL-2 deficiency
      induced peripheral autoimmunity) without brain IL-2 (two IL-2KO alleles) did not
      differ from SCID congenic mice with normal brain IL-2 (two WT IL-2 alleles);
      thus, contrary to our hypothesis, loss of brain-derived IL-2 did not affect
      learning acquisition in the water-maze. Compared to adult WT littermates (9
      weeks), adult IL-2KO mice with autoimmunity exhibited alterations in learning
      acquisition in the Morris water-maze whereas younger pre-autoimmune IL-2KO mice
      (5 weeks) had performance comparable to younger WT littermates, suggesting that
      the water-maze learning deficits in IL-2KO mice were associated with the
      development of peripheral autoimmunity. As IL-2KO mice have cytoarchitectural
      alterations in the dentate gyrus, circuitry involved in the differentiation of
      contexts (versus places), we also compared IL-2KO mice and littermates in a
      contextual fear discrimination paradigm. IL-2KO mice were found to have reduced
      conditioned fear discrimination that was not related to age-associated
      autoimmunity. Together, these findings suggest that complex interactions between
      IL-2 deficiency in the brain and immune system may modify brain processes
      involved in different modalities of learning and memory.

PMID- 25961068
TI  - Diagnostic performance of the "Huffing and Puffing" sign in psychogenic
      (functional) movement disorders.
AB  - OBJECTIVE: To determine the diagnostic value of effort-associated behaviors
      ("huffing and puffing" spectrum) in patients with psychogenic movement disorders.
      METHODS: Three blinded clinicians rated presence, severity, and duration of
      effort-associated features during standing and walking tasks on edited videos of
      131 patients with psychogenic gait disorders and 37 patients with organic gait
      disorders. RESULTS: Huffing, grunting, grimacing, and breath holding were the
      most common effort-associated behaviors in patients with psychogenic gait
      disorders, with a combined prevalence of 44% and disproportionate to the severity
      of gait impairment compared to organic gait disorders. The presence of "huffing
      and puffing"-type behaviors yielded a relatively low sensitivity but high
      specificity for the diagnosis of psychogenic movement disorders, increasing the
      odds of diagnosis 13-fold (95%, CI: 4.2-43.8) compared to organic gait disorders.
      CONCLUSIONS: Demonstration of effort-associated behaviors during standing and
      walking strongly supports the psychogenic nature of disorders when gait is
      involved.

PMID- 25961069
TI  - Signaling pathways in osteogenesis and osteoclastogenesis: Lessons from cranial
      sutures and applications to regenerative medicine.
AB  - One of the simplest models for examining the interplay between bone formation and
      resorption is the junction between the cranial bones. Although only roughly a
      quarter of patients diagnosed with craniosynostosis have been linked to known
      genetic disturbances, the molecular mechanisms elucidated from these studies have
      provided basic knowledge of bone homeostasis. This work has translated to methods
      and advances in bone tissue engineering. In this review, we examine the current
      knowledge of cranial suture biology derived from human craniosynostosis syndromes
      and discuss its application to regenerative medicine.

PMID- 25961070
TI  - Epigenetics and Osteoarthritis.
AB  - Osteoarthritis (OA) is the most common form of joint disease and the leading
      cause of chronic disability in middle-aged and older populations. The development
      of disease-modifying therapy for OA currently faces major obstacles largely
      because the regulatory mechanisms for the function of joint tissue cells remain
      unclear. Previous studies have found that the alterations in gene expression of
      specific transcription factors (TFs), pro- or anti-inflammatory cytokines, matrix
      proteinases and extracellular matrix (ECM) proteins in articular cartilage may be
      involved in the development of OA. However, the regulatory mechanisms for the
      expression of those genes in OA chondrocytes are largely unknown. The recent
      advances in epigenetic studies have shed lights on the importance of epigenetic
      regulation of gene expression in the development of OA. In this review, we
      summarize and discuss the recent studies on the regulatory roles of various
      epigenetic mechanisms in the expression of genes for specific TFs, cytokines, ECM
      proteins and matrix proteinases, as well the significance of these epigenetic
      mechanisms in the pathogenesis of OA.

PMID- 25961071
TI  - The effect of changes in lower incisor inclination on gingival recession.
AB  - AIM: Orthodontic treatment may promote development of recessions. The mechanism
      by which orthodontic treatment influences occurrence of recessions remains
      unclear. The aim of this study was to test the hypothesis that a change of
      mandibular incisor inclination promotes development of labial gingival
      recessions. MATERIALS AND METHODS: The study sample comprised dental casts and
      lateral cephalograms obtained from 109 subjects before orthodontic treatment (Tb)
      and after orthodontic treatment (Ta). Depending on the change of lower incisor
      inclination during treatment, the subjects were divided into three groups:
      Retroclination (R), Stable Position (S), and Proclination (P). The presence of
      gingival recessions of mandibular incisors and clinical crown heights were
      assessed on plaster models. RESULTS AND CONCLUSIONS: From Tb to Ta, Inc_Incl
      showed a statistically significant change in the R, P, and S groups (p < 0.05).
      Increase of clinical crown heights of the lower incisors (42, 4, and 31) was not
      statistically significant in any group. The only statistically significant
      intergroup difference was the greater increase of the clinical crown height of
      tooth number 32 in the P group in comparison with the R group (p = 0.049). The
      change of lower incisor inclination during treatment did not lead to development
      of labial gingival recessions in the study sample.

PMID- 25961073
TI  - Reflective optics design for an LED high beam headlamp of motorbikes.
AB  - We propose a reflective optics design for an LED motorbike high beam lamp. We set
      the measuring screen as an elliptical zone and divide it into many small lattices
      and divide the spatial angle of the LED source into many parts and make
      relationships between them. According to the conservation law of energy and the
      Snell's law, the reflector is generated by freeform optics design method. Then
      the optical system is simulated by Monte Carlo method using ASAP software. Light
      pattern of simulation could meet the standard. The high beam headlamp is finally
      fabricated and assembled into a physical object. Experiment results can fully
      comply with United Nations Economic Commission for Europe (ECE) vehicle
      regulations R113 revision 2 (Class C). 

PMID- 25961074
TI  - Sparse Matrix for ECG Identification with Two-Lead Features.
AB  - Electrocardiograph (ECG) human identification has the potential to improve
      biometric security. However, improvements in ECG identification and feature
      extraction are required. Previous work has focused on single lead ECG signals.
      Our work proposes a new algorithm for human identification by mapping two-lead
      ECG signals onto a two-dimensional matrix then employing a sparse matrix method
      to process the matrix. And that is the first application of sparse matrix
      techniques for ECG identification. Moreover, the results of our experiments
      demonstrate the benefits of our approach over existing methods. 

PMID- 25961075
TI  - Recognizing cursive typewritten text using segmentation-free system.
AB  - Feature extraction plays an important role in text recognition as it aims to
      capture essential characteristics of the text image. Feature extraction
      algorithms widely range between robust and hard to extract features and noise
      sensitive and easy to extract features. Among those feature types are statistical
      features which are derived from the statistical distribution of the image pixels.
      This paper presents a novel method for feature extraction where simple
      statistical features are extracted from a one-pixel wide window that slides
      across the text line. The feature set is clustered in the feature space using
      vector quantization. The feature vector sequence is then injected to a
      classification engine for training and recognition purposes. The recognition
      system is applied to a data corpus which includes cursive Arabic text of more
      than 600 A4-size sheets typewritten in multiple computer-generated fonts. The
      system performance is compared to a previously published system from the
      literature with a similar engine but a different feature set. 

PMID- 25961072
TI  - Implication of fructans in health: immunomodulatory and antioxidant mechanisms.
AB  - Previous studies have shown that fructans, a soluble dietary fiber, are
      beneficial to human health and offer a promising approach for the treatment of
      some diseases. Fructans are nonreducing carbohydrates composed of fructosyl units
      and terminated by a single glucose molecule. These carbohydrates may be straight
      or branched with varying degrees of polymerization. Additionally, fructans are
      resistant to hydrolysis by human digestive enzymes but can be fermented by the
      colonic microbiota to produce short chain fatty acids (SCFAs), metabolic by
      products that possess immunomodulatory activity. The indirect role of fructans in
      stimulating probiotic growth is one of the mechanisms through which fructans
      exert their prebiotic activity and improve health or ameliorate disease. However,
      a more direct mechanism for fructan activity has recently been suggested;
      fructans may interact with immune cells in the intestinal lumen to modulate
      immune responses in the body. Fructans are currently being studied for their
      potential as "ROS scavengers" that benefit intestinal epithelial cells by
      improving their redox environment. In this review, we discuss recent advances in
      our understanding of fructans interaction with the intestinal immune system, the
      gut microbiota, and other components of the intestinal lumen to provide an
      overview of the mechanisms underlying the effects of fructans on health and
      disease. 

PMID- 25961076
TI  - Application of machine learning method in genomics and proteomics.

PMID- 25961077
TI  - Briefing in application of machine learning methods in ion channel prediction.
AB  - In cells, ion channels are one of the most important classes of membrane proteins
      which allow inorganic ions to move across the membrane. A wide range of
      biological processes are involved and regulated by the opening and closing of ion
      channels. Ion channels can be classified into numerous classes and different
      types of ion channels exhibit different functions. Thus, the correct
      identification of ion channels and their types using computational methods will
      provide in-depth insights into their function in various biological processes. In
      this review, we will briefly introduce and discuss the recent progress in ion
      channel prediction using machine learning methods. 

PMID- 25961078
TI  - Development and Validation of the Alzheimer's Questionnaire (AQ).
AB  - The Alzheimer's Questionnaire (AQ) was developed to be brief and accurate
      informant-based assessment for primary care and geriatric physicians to use in
      screening for cognitive impairment. To date, several studies have been carried
      out and published establishing the diagnostic accuracy and psychometric validity
      of the AQ. This paper will provide a review of the studies that have been carried
      out to establish the AQ as a valid and accurate informant-based assessment of
      cognitive function.

PMID- 25961080
TI  - A letter from the National Colorectal Cancer Roundtable.

PMID- 25961079
TI  - Rapid Markovnikov addition of HCl to a pendant alkyne: evidence for a quinoidal
      cumulene.
AB  - Reaction of cis-[RuCl2(dppm)2]BF4 with TlBF4 and 1,4-diethynyl-benzenes results
      in the formation of the vinylidene cations trans-[Ru([double bond, length as m
      dash]C[double bond, length as m-dash]CH-C6H2-2,5-R2-4-C[triple bond, length as m
      dash]CH)Cl(dppm)2](+) (R = H, Me). Subsequent reaction with [N(n)Bu4]Cl results
      in nucleophilic attack at the coordinated organic ligand, but not at the expected
      metal-bound carbon atom. Instead, trans-[Ru(C[triple bond, length as m-dash]C
      C6H2-2,5-R2-4-CCl[double bond, length as m-dash]CH2)Cl(dppm)2] was generated
      which, when coupled with DFT calculations, provides evidence for an intermediate
      quinoidal cumulene complex. 

PMID- 25961082
TI  - Mapmaking.

PMID- 25961081
TI  - Emergency medicine point-of-care ultrasonography:   a national needs assessment
      of competencies for   general and expert practice.
AB  - INTRODUCTION: Emergency medicine point-of-care ultrasonography (EM-PoCUS) is a
      core competency for residents in the Royal College of Physicians and Surgeons of
      Canada and College of Family Physicians of Canada emergency medicine (EM)
      training programs. Although EM-PoCUS fellowships are currently offered in Canada,
      there is little consensus regarding what training should be included in a
      Canadian EM-PoCUS fellowship curriculum or how this contrasts with the training
      received in an EM residency.Objectives To conduct a systematic needs assessment
      of major stakeholders to define the essential elements necessary for a Canadian
      EM-PoCUS fellowship training curriculum. METHODS: We carried out a national
      survey of experts in EM-PoCUS, EM residency program directors, and EM residents.
      Respondents were asked to identify competencies deemed either nonessential to EM
      practice, essential for general EM practice, essential for advanced EM practice,
      or essential for EM-PoCUS fellowship trained (''expert'') practice. RESULTS: The
      response rate was 81% (351 of 435). PoCUS was deemed essential to general EM
      practice for basic cardiac, aortic, trauma, and procedural imaging. PoCUS was
      deemed essential to advanced EM practice in undifferentiated symptomatology,
      advanced chest pathologies, and advanced procedural applications. Expert-level
      PoCUS competencies were identified for administrative, pediatric, and advanced
      gynecologic applications. Eighty-seven percent of respondents indicated that
      there was a need for EM-PoCUS fellowships, with an ideal length of 6 months.
      CONCLUSION: This is the first needs assessment of major stakeholders in Canada to
      identify competencies for expert training in EM-PoCUS. The competencies should
      form the basis for EM-PoCUS fellowship programs in Canada.

PMID- 25961083
TI  - Vasopressor and inotrope use in Canadian emergency departments: evidence based
      consensus guidelines.

PMID- 25961084
TI  - David T. Yue: in memoriam.

PMID- 25961085
TI  - Cytarabine, venous catheter removal, sepsis, diagnosis of malignancy, and
      takotsubo syndrome. Reply by Baumann et al.

PMID- 25961086
TI  - Recognition: Build a reputation.

PMID- 25961087
TI  - Physicians judging medical negligence:  a conflict of values.

PMID- 25961088
TI  - Undescended ovary mimicking  appendiceal mucocele.

PMID- 25961089
TI  - Advanced segmental atrophy of the  liver with marked elastosis.

PMID- 25961090
TI  - Pyoderma gangrenosum after inguinal  hernia repair.

PMID- 25961091
TI  - Successive overrelaxation for laplacian support vector machine.
AB  - Semisupervised learning (SSL) problem, which makes use of both a large amount of
      cheap unlabeled data and a few unlabeled data for training, in the last few
      years, has attracted amounts of attention in machine learning and data mining.
      Exploiting the manifold regularization (MR), Belkin et al. proposed a new
      semisupervised classification algorithm: Laplacian support vector machines
      (LapSVMs), and have shown the state-of-the-art performance in SSL field. To
      further improve the LapSVMs, we proposed a fast Laplacian SVM (FLapSVM) solver
      for classification. Compared with the standard LapSVM, our method has several
      improved advantages as follows: 1) FLapSVM does not need to deal with the extra
      matrix and burden the computations related to the variable switching, which make
      it more suitable for large scale problems; 2) FLapSVM's dual problem has the same
      elegant formulation as that of standard SVMs. This means that the kernel trick
      can be applied directly into the optimization model; and 3) FLapSVM can be
      effectively solved by successive overrelaxation technology, which converges
      linearly to a solution and can process very large data sets that need not reside
      in memory. In practice, combining the strategies of random scheduling of
      subproblem and two stopping conditions, the computing speed of FLapSVM is rigidly
      quicker to that of LapSVM and it is a valid alternative to PLapSVM.

PMID- 25961092
TI  - Frederick J. de Serres Jr. (1929-2014).

PMID- 25961093
TI  - CardioPulse: big heart disease: new insights from studies of a million people.

PMID- 25961094
TI  - CardioPulse: the 'Young Thrombosis Researchers Group' of the ESC Working Group on
      Thrombosis.

PMID- 25961095
TI  - CardioPulse: the burden of cardiovascular disease in India.

PMID- 25961096
TI  - CardioPulse: the atrial septal defect: do we know everything?

PMID- 25961097
TI  - CardioPulse: drinking tea reduces non-cardiovascular   mortality by 24%.

PMID- 25961098
TI  - Standards for MSWs.

PMID- 25961099
TI  - Patient safety whistleblowing report published.

PMID- 25961100
TI  - Birth rate down as CS increases.

PMID- 25961101
TI  - Revised NMC code.

PMID- 25961102
TI  - Mandatory FGM reporting.

PMID- 25961103
TI  - The end of supervison?

PMID- 25961104
TI  - Seven-day services.

PMID- 25961105
TI  - 'Normality' in 2015.

PMID- 25961106
TI  - The code.

PMID- 25961107
TI  - Updating a B. anthracis Risk Model with Field Data from a Bioterrorism Incident.
AB  - In this study, a Bayesian framework was applied to update a model of pathogen
      fate and transport in the indoor environment. Distributions for model parameters
      (e.g., release quantity of B. anthracis spores, risk of illness, spore setting
      velocity, resuspension rate, sample recovery efficiency, etc.) were updated by
      comparing model predictions with measurements of B. anthracis spores made after
      one of the 2001 anthrax letter attacks. The updating process, which was
      implemented by using Markov chain Monte Carlo (MCMC) methods, significantly
      reduced the uncertainties of inputs with uniformed prior estimates: total
      quantity of spores released, the amount of spores exiting the room, and risk to
      occupants. In contrast, uncertainties were not greatly reduced for inputs for
      which informed prior data were available: deposition rates, resuspension rates,
      and sample recovery efficiencies. This suggests that prior estimates of these
      quantities that were obtained from a review of the technical literature are
      consistent with the observed behavior of spores in an actual attack. Posterior
      estimates of mortality risk for people in the room, when the spores were
      released, are on the order of 0.01 to 0.1, which supports the decision to
      administer prophylactic antibiotics. Multivariate sensitivity analyses were
      conducted to assess how effective different measurements were at reducing
      uncertainty in the estimated risk for the prior scenario. This analysis revealed
      that if the size distribution of the released particulates is known, then
      environmental sampling can be limited to accurately characterizing floor
      concentrations; otherwise, samples from multiple locations, as well as
      particulate and building air circulation parameters, need to be measured. 

PMID- 25961108
TI  - Impact on rotavirus gastro-enteritis hospitalisation during the first year of
      universal vaccination in Sicily.

PMID- 25961109
TI  - Phototriggered functionalization of hierarchically structured polymer brushes.
AB  - The precise design of bioactive surfaces, essential for the advancement of many
      biomedical applications, depends on achieving control of the surface architecture
      as well as on the ability to attach bioreceptors to antifouling surfaces. Herein,
      we report a facile avenue toward hierarchically structured antifouling polymer
      brushes of oligo(ethylene glycol) methacrylates via surface-initiated atom
      transfer radical polymerization (SI-ATRP) presenting photoactive tetrazole
      moieties, which permitted their functionalization via nitrile imine-mediated
      tetrazole-ene cyclocloaddition (NITEC). A maleimide-functional ATRP initiator was
      photoclicked to the side chains of a brush enabling a subsequent polymerization
      of carboxybetaine acrylamide to generate a micropatterned graft-on-graft polymer
      architecture as evidenced by X-ray photoelectron spectroscopy (XPS) and time-of
      flight secondary ion mass spectrometry (ToF-SIMS). Furthermore, the spatially
      resolved biofunctionalization of the tetrazole-presenting brushes was accessed by
      the photoligation of biotin-maleimide and subsequent binding of streptavidin. The
      functionalized brushes bearing streptavidin were able to resist the fouling from
      blood plasma (90% reduction with respect to bare gold). Moreover, they were
      employed to demonstrate a model biosensor by immobilization of a biotinylated
      antibody and subsequent capture of an antigen as monitored in real time by
      surface plasmon resonance. 

PMID- 25961110
TI  - DNA repair genes XRCC1 and ERCC1 polymorphisms and the risk of sporadic breast
      cancer in Han women in the Gansu Province of China.
AB  - AIMS: Polymorphisms in DNA damage repair genes may affect DNA repair capacity and
      modulate breast cancer susceptibility. In this study, we aimed to analyze two
      polymorphisms for each of the DNA repair genes X-ray repair cross-complementing
      group 1 (XRCC1) rs25487 and rs1799782 and excision repair cross-complementing
      group 1 (ERCC1) rs3212964 and rs11615, to evaluate their associations with the
      risk of sporadic breast cancer in Han women in the Gansu Province of China.
      METHODS: Genotypes were determined by a polymerase chain reaction-based approach
      for 101 patients with breast cancer and in 101 disease-free controls. RESULTS: We
      found that individuals with the AA genotype at XRCC1 rs25487 had a significantly
      increased risk of breast cancer compared with GG genotype (p<0.001, odds ratio
      [OR]=6.39, 95% confidence interval [CI]: 2.18-18.65). The dominant model showed
      that the combined rs25487 genotypes (AA+AG) increased the disease risk (p<0.001,
      OR=3.17, 95% CI: 1.76-5.72). However, no statistical associations were found
      between rs1799782 in XRCC1, or rs3212964 and rs11615 in ERCC1 and the risk of
      disease. In haplotype analysis, the GC haplotype in XRCC1 conferred an increased
      risk (p<0.001) with a 4.78-fold increase for each copy (95% CI: 2.52-8.72).
      Significant associations were also shown between the single nucleotide
      polymorphisms (SNPs) and the status of estrogen receptor (ER), progesterone
      receptor (PR), and HER-2. CONCLUSIONS: The results suggest that the XRCC1 rs25487
      polymorphism may increase the risk of breast cancer.

PMID- 25961111
TI  - Airway Remodeling in Preschool Children with Severe Recurrent Wheeze.
AB  - RATIONALE: Airway wall structure in preschoolers with severe recurrent wheeze is
      poorly described. OBJECTIVES: To describe airway wall structure and inflammation
      in preschoolers with severe recurrent wheeze. METHODS: Flexible bronchoscopy was
      performed in two groups of preschoolers with severe recurrent wheeze: group 1,
      less than or equal to 36 months (n = 20); group 2, 36-59 months (n = 29). We
      assessed airway inflammation, reticular basement membrane (RBM) thickness, airway
      smooth muscle (ASM), mucus gland area, vascularity, and epithelial integrity.
      Comparisons were then made with biopsies from 21 previously described
      schoolchildren with severe asthma (group 3, 5-11.2 yr). MEASUREMENTS AND MAIN
      RESULTS: RBM thickness was lower in group 1 than in group 2 (3.3 vs. 3.9 MUm; P =
      0.02), was correlated with age (P < 0.01; rho = 0.62), and was higher in
      schoolchildren than in preschoolers (6.8 vs. 3.8 MUm; P < 0.01). ASM area was
      lower in preschoolers than in schoolchildren (9.8% vs. 16.5%; P < 0.01).
      Vascularity was higher in group 1 than in group 2 (P = 0.02) and group 3 (P <
      0.05). Mucus gland area was higher in preschoolers than in schoolchildren (16.4%
      vs. 4.6%; P < 0.01). Inflammatory cell counts in biopsies were not correlated
      with airway wall structure. ASM area was higher in preschoolers with atopy than
      without atopy (13.1% vs. 7.7%; P = 0.01). Airway morphometrics and inflammation
      were similar in viral and multiple-trigger wheezers. CONCLUSIONS: In preschoolers
      with severe recurrent wheeze, markers of remodeling and inflammation are
      unrelated, and atopy is associated with ASM. In the absence of control subjects,
      we cannot determine whether differences observed in RBM thickness and vascularity
      result from disease or normal age-related development.

PMID- 25961112
TI  - Newly observed temperature and surface ligand dependence of electron mobility in
      indium oxide nanocrystals solids.
AB  - We developed a new class of organic surface ligands; 2-aminopyridine (2AP), 4
      aminobenzoic acid (4ABA), and benzoic acid (BA); for use in the solution ligand
      exchange of nanocrystals (NCs) in the presence of nitric acid (HNO3). Here,
      colloidal NCs synthesis is used for the first time. These short, air-stable, easy
      to-model ligands bind to the surface of the indium oxide nanocrystal (In2O3 NC)
      and provide the electrostatic stabilization of NC semiconductor dispersions in
      N,N-dimethylformamide, allowing for a solution-based deposition of NCs into thin
      film transitors (TFTs). The shorter organic ligands greatly facilitate electronic
      coupling between the NCs. For example, thin films made from 2AP-capped In2O3 NCs
      exhibited a high electron mobility of MU~9.5 cm2/(V.s), an on-off current ratio
      of about >10(7), and a subthreshold swing of 2.34 V/decade. As the ligand length
      decreased, the electron mobility increased exponentially. Furthermore, we also
      report on the temperature-dependent behavior of the electron transport of In2O3
      NCs films, in the case in which thin films were cured at 150  degrees C, as the
      2AP, BA, and 4ABA ligand molecules were sustained on the NC. We demonstrated a
      hopping transport mechanism instead of a band-like transport, and the thermally
      activated carrier transport process governed the charge transport in our In2O3 NC
      thin-film solid.

PMID- 25961113
TI  - Long Working-Distance Optical Trap for in Situ Analysis of Contact-Induced Phase
      Transformations.
AB  - A novel optical trapping technique is described that combines an upward
      propagating Gaussian beam and a downward propagating Bessel beam. Using this
      optical arrangement and an on-demand droplet generator makes it possible to
      rapidly and reliably trap particles with a wide range of particle diameters (~1.5
      25 MUm), in addition to crystalline particles, without the need to adjust the
      optical configuration. Additionally, a new image analysis technique is described
      to detect particle phase transitions using a template-based autocorrelation of
      imaged far-field elastically scattered laser light. The image analysis allows
      subtle changes in particle characteristics to be quantified. The instrumental
      capabilities are validated with observations of deliquescence and homogeneous
      efflorescence of well-studied inorganic salts. Then, a novel collision-based
      approach to seeded crystal growth is described in which seed crystals are
      delivered to levitated aqueous droplets via a nitrogen gas flow. To our
      knowledge, this is the first account of contact-induced phase changes being
      studied in an optical trap. This instrument offers a novel and simple analytical
      technique for in situ measurements and observations of phase changes and crystal
      growth processes relevant to atmospheric science, industrial crystallization,
      pharmaceuticals, and many other fields. 

PMID- 25961114
TI  - DHEA replacement for postmenopausal women: have we been looking in the right
      direction?
AB  - Dehydroepiandrosterone (DHEA) and its sulfate represent the most abundant sex
      steroid in humans. In addition to age-related reduction, serum DHEA shows large
      interindividual variability. Although cross-sectional studies suggest that lower
      levels are associated with cardiovascular, cognitive and sexual impairment in
      women, clinical trials of oral DHEA replacement have failed to show benefits.
      However, current evidence is too imprecise to draw definite conclusions. 

PMID- 25961115
TI  - Predictors of postevent distress and growth among firefighters after work-related
      emergencies--A cross-national study.
AB  - Firefighters may experience posttraumatic stress symptomatology (i.e., postevent
      distress) as a consequence of exposure to work-related distressing incidents.
      However, positive psychological changes (i.e., postevent growth) should also be
      taken into account. The aim of this cross-national study was to investigate both
      postevent distress and growth in firefighters following distressing incidents. A
      sample of 1,916 firefighters from 8 predominantly European countries recalled a
      work-related distressing incident. Two hierarchical regression analyses were run
      to reveal predictors of postevent distress and growth, respectively. Predictors
      included person pre-event characteristics, objective (e.g., type of incident,
      time since incident, fatalities) and subjective (e.g., perceived life-threat,
      peri-event distress, most distressing aspect) incident features, and the
      participant's country. Postevent distress was measured by the Impact of Event
      Scale-Revised (IES-R) and growth by the Posttraumatic Growth Inventory-Short Form
      (PTGI-SF). The final models explained 29% of the variation in postevent distress
      and 26% in growth. Postevent distress and growth were predicted by different
      variables. Country differences were found after controlling for all other
      variables. Further research is needed to explain these differences.

PMID- 25961116
TI  - Optimism predicts positive health in repatriated prisoners of war.
AB  - "Positive health," defined as a state beyond the mere absence of disease, was
      used as a model to examine factors for enhancing health despite extreme trauma.
      The study examined the United States' longest detained American prisoners of war,
      those held in Vietnam in the 1960s through early 1970s. Positive health was
      measured using a physical and a psychological composite score for each
      individual, based on 9 physical and 9 psychological variables. Physical and
      psychological health was correlated with optimism obtained postrepatriation
      (circa 1973). Linear regressions were employed to determine which variables
      contributed most to health ratings. Optimism was the strongest predictor of
      physical health (beta = -.33, t = -2.73, p = .008), followed by fewer sleep
      complaints (beta = -.29, t = -2.52, p = .01). This model accounted for 25% of the
      variance. Optimism was also the strongest predictor of psychological health (beta
      = -.41, t = -2.87, p = .006), followed by Minnesota Multiphasic Personality
      Inventory-Psychopathic Deviate (MMPI-PD; McKinley & Hathaway, 1944) scores (beta
      = -.23, t = -1.88, p = .07). This model strongly suggests that optimism is a
      significant predictor of positive physical and psychological health, and optimism
      also provides long-term protective benefits. These findings and the utility of
      this model suggest a promising area for future research and intervention.

PMID- 25961118
TI  - Perceived resilience: Examining impacts of the deepwater horizon oil spill one
      year post-spill.
AB  - Scant research has focused on resilient responding to disasters such as oil
      spills a year or more after the event. One year after the BP Deepwater Horizon
      oil spill, this study assessed perceived resilience, relations between resiliency
      and psychological symptoms, and the degree to which self-reported resiliency was
      associated with reduced psychological symptoms after accounting for differences
      in economic impact sustained by Gulf Coast residents. Participants were 812
      adults (64% women, mean age 50) of 2 Alabama coastal communities. Participants
      were administered a telephone survey 1-year post-spill assessing self-perceptions
      of impact factors (e.g., economic and social), resilience, coping, and depressive
      and PTSD symptoms. Most participants perceived themselves as resilient (n = 739).
      As expected, lower perceived resilience was associated with greater ongoing
      depressive and PTSD symptoms. Spill-related economic impact predicted greater
      depressive and PTSD symptoms; however, perceived resilience predicted significant
      variance in psychological symptoms after taking into account spill-related
      economic impact. Improving individuals' sense of resiliency may help mitigate
      psychosocial and mental health effects over time.

PMID- 25961117
TI  - Orthostatic hypotension in young adults with and without posttraumatic stress
      disorder.
AB  - The purpose of this research is (a) to evaluate differences in orthostatic
      hypotension (OH) among young adults with and without posttraumatic stress
      disorder (PTSD) and (b) to examine whether group differences may be attributable
      to behavioral risk factors frequently associated with PTSD. Volunteers and U.S.
      veterans 18 to 39 years old (N = 222) completed a semistructured interview
      assessment of PTSD status. Direct measurements were obtained for supine and
      standing systolic and diastolic blood pressure at study visits, as well as height
      and weight, from which body mass index (BMI) was calculated. After controlling
      for use of psychotropic medications, a logistic regression model revealed that
      PTSD status was positively associated with OH, such that participants with PTSD
      were at 4.51 greater odds of having OH than control participants. Moreover, this
      effect was partially mediated by lifetime alcohol dependence (bootstrapped 95%
      confidence interval [-0.83, -0.20]). Overall, PTSD may pose a significant risk
      for OH among younger adults. In the present sample, this relationship was
      primarily driven by the disproportionately high history of alcohol dependence
      among individuals with PTSD. These results suggest that traditional therapy for
      PTSD should be coupled with treatment for alcohol dependency, when applicable, to
      reap both psychological and physiological benefits.

PMID- 25961119
TI  - Posttraumatic stress predicting depression and social support among college
      students: Moderating effects of race and gender.
AB  - More than half of the students entering college report a history of potentially
      traumatic events; however, little is known about the relationship of trauma
      exposure and posttraumatic stress disorder (PTSD) symptomatology to college
      students' mental health and access to social support or whether these
      relationships may show variations as a function of race and gender. The purpose
      of this study was to explore whether the relationships between PTSD symptoms and
      both depression and social support were moderated by gender and race. Data were
      collected from 631 African American (AA) and 299 European American (EA) freshmen
      students attending 2 universities in the Southeast. The majority of the students
      (74.3% of the AA and 68.2% of the EA sample) reported lifetime exposure to at
      least 1 traumatic event. PTSD symptomatology was significantly and positively
      associated with depression symptoms for all groups (i.e., AA and EA males and
      females); however, the relationship between these 2 variables was strongest for
      EA men. Similarly, the relationship between PTSD symptoms on the avoidance
      cluster and social support was stronger for EA males than other groups; avoidance
      symptoms did not significantly predict social support for AA men.

PMID- 25961120
TI  - Predictors of expressive writing content and posttraumatic stress following a
      mass shooting.
AB  - This study examined relations among experiential avoidance, state dissociation
      during writing, cognitive-emotional processing, and posttraumatic stress in the
      context of an expressive writing task among 58 undergraduate females who were
      students at a large midwestern university that had recently experienced a mass
      shooting. Experiential avoidance significantly predicted reported suppression
      during the writing task. Additionally, posttraumatic stress symptoms (PTSS) at
      the time of the writing task were significantly associated with state
      dissociation, suppression, and the use of positive emotion words during the
      writing. Finally, at the zero-order level, prospective PTSS were associated with
      state dissociation and suppression during the earlier writing task. However, in a
      full regression model, only experiential avoidance and PTSS at the time of the
      writing task significantly predicted prospective PTSS. Supplemental analyses
      suggest processes may operate differently across levels of exposure. Findings
      from the present study provide further support for the role of experiential
      avoidance, state dissociation during writing, and cognitive-emotional processing
      in predicting PTSS. Additionally, experiential avoidance may play an important
      role in how individuals use cognitive-emotional processing to narrate a traumatic
      event.

PMID- 25961121
TI  - Linguistic characteristics in a non-trauma-related narrative task are associated
      with PTSD diagnosis and symptom severity.
AB  - Linguistic characteristics of trauma narratives have been linked to the
      development and severity of posttraumatic stress disorder (PTSD). However, it
      remains unclear if linguistic markers of PTSD exist beyond the scope of trauma
      narratives. This study used ambiguous visual prompts to elicit spontaneous
      narratives from trauma-exposed individuals with (n = 23) and without PTSD (n =
      30). Individuals with PTSD used more singular pronouns and death-related words,
      and fewer plural pronouns. Within the PTSD group, increased severity of
      reexperiencing symptoms was associated with greater use of singular pronouns and
      lower use of cognitive words; increased severity of avoidance symptoms was
      associated with lower use of death words; and increased severity of hyperarousal
      symptoms was associated with less frequent use of anxiety words. Together, these
      linguistic variables accounted for 53% of the variance in total PTSD symptom
      severity. These findings are consistent with previous research suggesting that
      language use is a strong predictor of PTSD psychopathology, and extend the
      evidence to include the linguistic characteristics of non-trauma-related
      narratives.

PMID- 25961122
TI  - Outer retina reflectivity changes on sd-oct after intravitreal ocriplasmin for
      vitreomacular traction and macular hole.
AB  - PURPOSE: To report initial experience with intravitreal ocriplasmin (IVO) and to
      describe outer retina reflectivity changes observed on spectral domain optical
      coherence tomography (SD-OCT) after IVO injection in patients with vitreomacular
      traction (VMT) with or without macular holes (MHs). METHODS: A consecutive
      retrospective review of patients with VMT and MH who were treated with IVO was
      performed. Patients underwent complete ophthalmic evaluation, including
      nonstandardized Snellen visual acuity testing, and SD-OCT at baseline and follow
      up visits. RESULTS: A total of 23 patients who received IVO for VMT and/or MH
      were included for analysis. Patient age ranged from 53 years to 93 years with a
      mean of 74 years. The mean follow-up was 174 days (range: 20-291 days).
      Vitreomacular traction release at Day 30 after IVO was achieved in 11 of 23
      patients (47.82%), at an average of 14.54 days (range: 1-30 days) after
      treatment. The mean visual acuity improved from 0.50 to 0.38. At presentation,
      eight patients had MH associated with VMT. Closure of the MH with ocriplasmin was
      achieved in two patients, and six patients underwent pars plana vitrectomy for MH
      repair. Ten of 23 patients (43.47%) presented with changes in the outer retina
      reflectivity on SD-OCT after IVO, 4 patients of this group experienced a decrease
      in visual acuity. In 7 of these 10 patients (70%), VMT release was documented on
      OCT by Day 30 postinjection compared with 4 of 13 patients (30.76%) without outer
      retina changes post-IVO. Normalization of the outer retina reflectivity was
      achieved in all cases. CONCLUSION: In this case series of VMT/MH patients treated
      with ocriplasmin, changes in the SD-OCT outer retina reflectivity were relatively
      common. Within weeks, the outer retinal reflectivity on SD-OCT improved, as did
      the visual acuity. Further studies to investigate the association between outer
      retina reflectivity changes with the use of IVO and long-term visual acuity
      outcomes are warranted.

PMID- 25961123
TI  - RETINAL AND CHOROIDAL CHANGES OF NANOPHTHALMIC EYES WITH AND WITHOUT SECONDARY
      GLAUCOMA.
AB  - PURPOSE: To analyze the retinal and choroidal changes and their relationship in
      nanophthalmic eyes quantitatively and to evaluate the influence of axial length
      (AL) and secondary glaucoma on the retina and choroid in these eyes. METHODS:
      Thirty-seven eyes of 19 nanophthalmic patients (23 eyes with secondary glaucoma,
      SG group; 14 eyes without secondary glaucoma, NG group) and 38 eyes of 38 age/sex
      matched controls were recruited. The retinal and choroidal changes, the foveal
      retinal thickness (FRT), and the subfoveal choroidal thickness (SFCT) were
      measured by enhanced depth imaging optical coherence tomography (EDI-OCT,
      Heidelberg). The parameters were compared between nanophthalmic eyes and
      controls, as well as between the NG and SG group. The relationship between AL and
      FRT, AL and SFCT, and FRT and SFCT were analyzed. RESULTS: The optical coherence
      tomography images revealed broadened outer nuclear layer, and aberrant
      preservation of the inner retinal layer to different extents existed in the fovea
      in all nanophthalmic cases. The ganglion cell layer was found much thinner in the
      SG group than that of the NG group. The low-reflective areas near the outer
      border of the choroid in nanophthalmic eyes seemed larger than that of controls.
      The average FRT and SFCT of the total nanophthalmic cases were significantly
      thicker than those of controls (P < 0.001, P < 0.001, respectively). The FRT of
      the SG group was thinner than that of the NG group (P < 0.001). No significant
      difference was found between the SG group and NG group in SFCT (P = 0.83). Axial
      length was negatively related to FRT and SFCT (P < 0.001, P < 0.001,
      respectively). The foveal retinal thickness and SFCT were positively related (P =
      0.02). CONCLUSION: Retina and choroid are thickened accordantly in nanophthalmic
      eyes and are negatively related to AL. Secondary glaucoma could affect the FRT
      but would do nothing to the SFCT. The combined measurement of retina and choroid
      by enhanced depth imaging optical coherence tomography provides valuable
      information to facilitate comprehensive understanding of the pathology of
      nanophthalmos and its complications in vivo.

PMID- 25961124
TI  - VALIDATION OF AN ALGORITHM FOR NONMETALLIC INTRAOCULAR FOREIGN BODIES'
      COMPOSITION IDENTIFICATION BASED ON COMPUTED TOMOGRAPHY AND MAGNETIC RESONANCE
      IMAGING.
AB  - PURPOSE: To validate and evaluate the accuracy of an algorithm for the
      identification of nonmetallic intraocular foreign body composition based on
      computed tomography and magnetic resonance imaging. METHODS: An algorithm for the
      identification of 10 nonmetallic materials based on computed tomography and
      magnetic resonance imaging has been previously determined in an ex vivo porcine
      model. Materials were classified into 4 groups (plastic, glass, stone, and wood).
      The algorithm was tested by 40 ophthalmologists, which completed a questionnaire
      including 10 sets of computed tomography and magnetic resonance images of eyes
      with intraocular foreign bodies and were asked to use the algorithm to identify
      their compositions. Rates of exact material identification and group
      identification were measured. RESULTS: Exact material identification was achieved
      in 42.75% of the cases, and correct group identification in 65%. Using the
      algorithm, 6 of the materials were exactly identified by over 50% of the
      participants, and 7 were correctly classified according to their groups by over
      75% of the materials. DISCUSSION: The algorithm was validated and was found to
      enable correct identification of nonmetallic intraocular foreign body composition
      in the majority of cases. This is the first study to report and validate a
      clinical tool allowing intraocular foreign body composition based on their
      appearance in computed tomography and magnetic resonance imaging, which was
      previously impossible.

PMID- 25961125
TI  - Recent advances of catalytic asymmetric 1,3-dipolar cycloadditions.

PMID- 25961126
TI  - Photovoltaics: Perovskite cells charge forward.

PMID- 25961127
TI  - Cis-selective and highly enantioselective hydrogenation of 2,3,4-trisubstituted
      quinolines.
AB  - A highly enantioselective cis-hydrogenation of 2,3,4-trisubstituted quinolines
      has been realized for the first time using chiral borane catalysts generated in
      situ from chiral dienes. A variety of tetrahydroquinoline derivatives containing
      three contiguous stereogenic centers were obtained in 76-99% yields with 82-99%
      ee's. 

PMID- 25961128
TI  - The functional and clinical relevance of childhood trauma-related admixture of
      affective, anxious and psychosis symptoms.
AB  - OBJECTIVE: Previous work has shown that across different patient samples,
      patients with childhood trauma are more likely to have co-occurrence of
      affective, anxious and psychosis symptoms than non-traumatized patients. However,
      the clinical relevance of trauma-related admixture remains to be established.
      METHOD: We examined patients with mood disorder (NEMESIS-2; n = 1260), anxiety
      disorder (NEMESIS-2; n = 896) or psychotic disorder (GROUP; n = 532) in terms of
      symptom profiles, quality of life (QOL) and social functioning. RESULTS: Results
      showed that mood disorder patients with both trauma and co-occurrence of
      affective, anxious and psychosis symptoms had a lower QOL (B-12.6, 95% CI -17.7
      to -7.5, P < 0.001), more help-seeking behaviour [odds ratio (OR) 2.5, 95% CI 1.1
      5.7, P = 0.031] and higher prevalence of substance use disorders (OR 7.8, 95% CI
      1.1-58.0, P = 0.044), compared with patients without trauma history and symptom
      admixture (Trauma-/CL-). Similar results were found in patients with an anxiety
      disorder. Traumatized patients with a psychotic disorder and admixture showed
      lower QOL (B-0.6, 95% CI -0.9 to -0.4, P < 0.001), higher prevalence of drug
      disorders (OR 2.2, 95% CI 1.2-3.9, P = 0.008) and lower global assessment of
      functioning (B-12.8, 95% CI -17.1 to -8.5, P < 0.001) than Trauma-/CL- patients.
      CONCLUSION: Stratification according to childhood trauma exposure thus identifies
      a phenotype characterized by admixture of affective, anxiety and psychotic
      symptoms that, when combined, has clinical relevance. Identification of
      functionally meaningful aetiological subgroups may aid clinical practice.

PMID- 25961129
TI  - Why are standardized lifestyle interventions for the metabolic syndrome not
      successful? Experiences from two RCTs and one mixed-methods study.

PMID- 25961130
TI  - Fast Triplet Formation via Singlet Exciton Fission in a Covalent Perylenediimide
      beta-apocarotene Dyad Aggregate.
AB  - A covalent dyad was synthesized in which perylene-3,4,:9:10-bis(dicarboximide)
      (PDI) is linked to beta-apocarotene (Car) using a biphenyl spacer. The dyad is
      monomeric in toluene and forms a solution aggregate in methylcyclohexane (MCH).
      Using femtosecond transient absorption (fsTA) spectroscopy, the monomeric dyad
      and its aggregates were studied both in solution and in thin films. In toluene,
      photoexcitation at 530 nm preferentially excites PDI, and the dyad undergoes
      charge separation in tau = 1.7 ps and recombination in tau = 1.6 ns. In MCH and
      in thin solid films, 530 nm excitation of the PDI-Car aggregate also results in
      charge transfer that competes with energy transfer from (1)*PDI to Car and with
      an additional process, rapid Car triplet formation in <50 ps. Car triplet
      formation is only observed in the aggregated PDI-Car dyad and is attributed to
      singlet exciton fission (SF) within the aggregated PDI, followed by rapid triplet
      energy transfer from (3)*PDI to the carotenoid. SF from beta-apocarotene
      aggregation is ruled out by direct excitation of Car films at 414 nm, where no
      triplet formation is observed. Time-resolved electron paramagnetic resonance
      measurements on aggregated PDI-Car show the formation of (3)*Car with a spin
      polarization pattern that rules out radical-pair intersystem crossing as the
      mechanism of triplet formation as well. 

PMID- 25961131
TI  - Stretchable Wire-Shaped Asymmetric Supercapacitors Based on Pristine and MnO2
      Coated Carbon Nanotube Fibers.
AB  - While the emerging wire-shaped supercapacitors (WSS) have been demonstrated as
      promising energy storage devices to be implemented in smart textiles, challenges
      in achieving the combination of both high mechanical stretchability and excellent
      electrochemical performance still exist. Here, an asymmetric configuration is
      applied to the WSS, extending the potential window from 0.8 to 1.5 V, achieving
      tripled energy density and doubled power density compared to its asymmetric
      counterpart while accomplishing stretchability of up to 100% through the
      prestrainning-then-buckling approach. The stretchable asymmetric WSS constituted
      of MnO2/CNT hybrid fiber positive electrode, aerogel CNT fiber negative electrode
      and KOH-PVA electrolyte possesses a high specific capacitance of around 157.53
      MUF cm(-1) at 50 mV s(-1) and a high energy density varying from 17.26 to 46.59
      nWh cm(-1) with the corresponding power density changing from 7.63 to 61.55 MUW
      cm(-1). Remarkably, a cyclic tensile strain of up to 100% exerts negligible
      effects on the electrochemical performance of the stretchable asymmetric WSS.
      Moreover, after 10,000 galvanostatic charge-discharge cycles, the specific
      capacitance retains over 99%, demonstrating a long cyclic stability.

PMID- 25961133
TI  - Rebuttal to Comment on Authenticity and traceability of vanilla flavors by
      analysis of stable isotopes of carbon and hydrogen.

PMID- 25961132
TI  - A beginning of the end: new insights into the functional organization of
      telomeres.
AB  - Ever since the first demonstration of their repetitive sequence and unique
      replication pathway, telomeres have beguiled researchers with how they function
      in protecting chromosome ends. Of course much has been learned over the years,
      and we now appreciate that telomeres are comprised of the multimeric protein/DNA
      shelterin complex and that the formation of t-loops provides protection from DNA
      damage machinery. Deriving their name from D-loops, t-loops are generated by the
      insertion of the 3' overhang into telomeric repeats facilitated by the binding of
      TRF2. Recent studies have uncovered novel forms of chromosome end-structure that
      may implicate telomere organization in cellular processes beyond its essential
      role in telomere protection and homeostasis. In particular, we have recently
      described that t-loops form in a TRF2-dependent manner at interstitial telomere
      repeat sequences, which we termed interstitial telomere loops (ITLs). These
      structures are also dependent on association of lamin A/C, a canonical component
      of the nucleoskeleton that is mutated in myriad human diseases, including human
      segmental progeroid syndromes. Since ITLs are associated with telomere stability
      and require functional lamin A/C, our study suggests a mechanistic link between
      cellular aging (replicative senescence induced by telomere shortening) and
      organismal aging (modeled by Hutchinson Gilford Progeria Syndrome). Here we
      speculate on other potential ramifications of ITL formation, from gene expression
      to genome stability to chromosome structure. 

PMID- 25961134
TI  - Computational and experimental investigations of the formal dyotropic
      rearrangements of Himbert arene/allene cycloadducts.
AB  - The fascinating intramolecular arene/allene cycloaddition discovered by Himbert
      affords dearomatized, polycyclic intermediates with sufficient strain energy to
      drive rearrangement processes of the newly formed ring system. We disclose a
      detailed examination of a thermally induced stepwise dyotropic skeletal
      rearrangement of these cycloadducts, a reaction also first described by Himbert.
      We offer computational evidence for a two-stage mechanism for this formal
      dyotropic rearrangement and provide rationalizations for the significant
      substitution-dependent rate differences observed in experiments. These
      investigations led to the development of a Lewis-acid-catalyzed rearrangement of
      precursors that were unreactive under simple thermal instigation. The isolation
      of the product of an "interrupted" rearrangement under Lewis acidic conditions
      provides further support for the proposed stepwise mechanism. Computational
      results also matched experiments in terms of regiochemical preferences in
      unsymmetrical rearrangement precursors and explained why lactam O-, S-, and C
      heterologues do not easily undergo this rearrangement. 

PMID- 25961135
TI  - Age-Related Lipid Metabolic Signature in Human LMNA-Lipodystrophic Stem Cell
      Derived Adipocytes.
AB  - CONTEXT: Lamin A (LMNA)-linked lipodystrophies belong to a group of clinical
      disorders characterized by a redistribution of adipose tissue with a variable
      range of metabolic complications. The leading cause of these disorders is the
      nonphysiological accumulation of the lamin A precursor, prelamin A. However, the
      molecular mechanisms by which prelamin A induces the pathology remain unclear.
      OBJECTIVE: The aim of this study is to use an experimental LMNA-lipodystrophy
      model based on human mesenchymal stem cell (hMSC)-derived adipocytes that
      accumulate prelamin A to gain deeper insights into the mechanisms governing these
      diseases. DESIGN/SETTING/PARTICIPANTS: Prelamin A-induced or -noninduced hMSC
      derived adipocytes were obtained from healthy donors. The study was performed at
      the Biocruces Health Research Institute. MAIN OUTCOME MEASURES: Lipolytic
      activity was determined by the measurement of glycerol and free fatty acids.
      Ultrastructural analysis was performed by electron microscopy. Flow cytometry was
      used to assess mitochondrial membrane potential, and ultra-performance liquid
      chromatography coupled to mass spectrometry was used to explore lipid profiles.
      RESULTS: Prelamin A accumulating hMSC-derived adipocytes revealed increased
      lipolysis, mitochondrial dysfunction, and endoplasmic reticulum stress.
      Accumulation of prelamin A induces an altered lipid profile characterized by
      reduced diacylglyceride content, a higher ratio of monounsaturated over
      polyunsaturated fatty acids, and decreased stearoyl-coenzyme A desaturase-1
      activity. In contrast, the ratio of diacylglycerophosphatidylcholine over
      diacylglycerophosphatidylethanolamine and the activity of
      phosphatidylethanolamine-methyltransferase were increased. CONCLUSIONS: Prelamin
      A accumulation causes mitochondrial dysfunction, endoplasmic reticulum stress,
      and altered lipid metabolism resembling a premature aging phenotype.

PMID- 25961136
TI  - Daily or Cyclical Teriparatide Treatment in Women With Osteoporosis on no Prior
      Therapy and Women on Alendronate.
AB  - CONTEXT: Intermittent 3-month cyclic administration might optimize the anabolic
      potential of teriparatide (TPTD). OBJECTIVE: To determine whether 3-month
      cyclical TPTD would produce a similar bone mineral density (BMD) response to
      daily therapy in treatment naive (Rx-naive) women and to confirm the results in
      alendronate (ALN)-treated (ALN-Rx) women over 24 months. DESIGN: Subjects
      participated in a randomized open-label study for 2 years. SETTING: Osteoporosis
      clinical research center. PARTICIPANTS: A total of 150 postmenopausal women with
      osteoporosis in two cohorts: 86 Rx-naive and 64 ALN-Rx. INTERVENTION: Within
      cohorts, women were randomized to daily TPTD for 24 months or four 3-month TPTD
      cycles, each followed by 3 months off (12 mo total TPTD). MAIN OUTCOMES: BMD at
      24 months. RESULTS: In Rx-naive women, BMD increased in the lumbar spine (LS),
      total hip (TH), trochanter (Troch), and femoral neck (FN) in daily and cyclic
      groups (within groups, P < .0002, except cyclic FN, P = .13). Increases were 2
      fold greater in daily vs cyclic groups (LS, 8.8 vs 4.8%; TH, 4.0 vs 2.1%; Troch,
      5.6 vs 3.1%; and FN, 2.9 vs 1.2%; group differences, all P < .05). In daily vs
      cyclic groups, radius BMD declined (-4.2 vs -2.1%, respectively; both P < .01;
      group difference, P = .08) and total bone mineral increased modestly (1.4%, P =
      .18; vs 1.5%, P = .06; group difference, not significant). In ALN-Rx women, there
      were no group differences (daily vs cyclic: LS, 7.5 and 6.0%; TH, 3 and 2.5%;
      Troch, 3.7 and 3.3%; FN, 3 and 1.5%; within groups, P < .003; except cyclic FN, P
      = .2). In daily and cyclic groups, radius BMD decreased (-0.7% [not significant]
      and -1.4% [P < .05], respectively), and total bone mineral increased 2.3 and 3%
      (both P < .001). CONCLUSION: Cyclic TPTD over 2 years improves BMD similarly to
      daily treatment in women who remain on ALN, despite only 50% of the TPTD dose.
      However, there does not appear to be a BMD advantage to cyclic administration in
      treatment-naive women for up to 24 months.

PMID- 25961137
TI  - An investigation of emotional intelligence measures using item response theory.
AB  - This study investigated the psychometric properties of 3 frequently administered
      emotional intelligence (EI) scales (Wong and Law Emotional Intelligence Scale
      [WLEIS], Schutte Self-Report Emotional Intelligence Test [SEIT], and Trait
      Emotional Intelligence Questionnaire [TEIQue]), which were developed on the basis
      of different theoretical frameworks (i.e., ability EI and mixed EI). By
      conducting item response theory (IRT) analyses, the authors examined the item
      parameters and compared the fits of 2 response process models (i.e., dominance
      model and ideal point model) for these scales with data from 355 undergraduate
      sample recruited from the subject pool. Several important findings were obtained.
      First, the EI scales seem better able to differentiate individuals at low trait
      levels than high trait levels. Second, a dominance model showed better model fit
      to the self-report ability EI scale (WLEIS) and also fit better with most
      subfactors of the SEIT, except for the mood regulation/optimism factor. Both
      dominance and ideal point models fit a self-report mixed EI scale (TEIQue). Our
      findings suggest (a) the EI scales should be revised to include more items at
      moderate and higher trait levels; and (b) the nature of the EI construct should
      be considered during the process of scale development.

PMID- 25961138
TI  - Correction to Washburn et al. (2015).
AB  - Reports an error in "Assessing DSM-5 nonsuicidal self-injury disorder in a
      clinical sample" by Jason J. Washburn, Lauren M. Potthoff, K. R. Juzwin and
      Denise M. Styer (Psychological Assessment, 2015[Mar], Vol 27[1], 31-41). In the
      Method section, in the subsection Alexian Brothers Assessment of Self-Injury
      (ABASI), the first sentence of the third paragraph should read: "Examination of
      the specific NSI disorder criteria indicates the prominence of the first symptom
      in Criterion C. Symptom C-1, which evaluates the experience of interpersonal
      difficulties or negative thoughts or feelings immediately prior to engaging in
      selfinjury, was the most endorsed symptom of NSI disorder; 100% of those meeting
      criteria for NSI Disorder endorsed Symptom C-1 on the ABASI." (The following
      abstract of the original article appeared in record 2014-40800-001.) The entry
      for nonsuicidal self-injury (NSI) disorder in the 5th edition of the Diagnostic
      and Statistical Manual of Mental Disorders (DSM-5) provides a criterion-based
      definition of clinically relevant NSI. NSI disorder is currently classified in
      the DSM-5 as a condition requiring further study. The present study aimed to
      examine the reliability, validity, and clinical utility of a self-report measure
      of NSI disorder, the Alexian Brothers Assessment of Self-Injury (ABASI). The
      sample included 511 patients admitted to an acute care treatment program designed
      to treat NSI. Patients were administered the ABASI as part of a clinical
      assessment and routine outcome evaluation. The sample included a broad age range,
      as well as sufficient numbers of males and Hispanics to examine sociodemographic
      differences. The ABASI demonstrated adequate internal consistency and test-retest
      reliability, and the factor structure reflects NSI disorder criteria. Among
      patients being treated for NSI, 74% met criteria for NSI disorder. No differences
      in the rate of NSI disorder were observed by sex, ethnicity, or age. Although NSI
      disorder is associated with a worse presentation of self-injurious behavior, NSI
      disorder provides limited clinical utility as a dichotomous diagnosis, at least
      when compared with common NSI characteristics such as number of methods of NSI
      and the urge to self-injure. Instead, findings support a dimensional approach to
      NSI disorder. Analyses of specific symptoms of NSI disorder indicate concerns
      with Criterion B as currently defined by the DSM-5. Recommendations for a more
      parsimonious revision of NSI disorder are discussed.

PMID- 25961139
TI  - The Cultural Socialization Scale: Assessing family and peer socialization toward
      heritage and mainstream cultures.
AB  - In a culturally diverse society, youth learn about multiple cultures from a
      variety of sources, yet the existing assessment of cultural socialization has
      been limited to parents' efforts to teach youth about their heritage culture. The
      current study adapted and extended an existing cultural socialization measure
      (Umana-Taylor & Fine, 2004) to assess 4 types of socialization practices
      encountered specifically during adolescence: cultural socialization by families
      and peers toward both one's heritage culture and the mainstream culture. In a
      pilot study, we developed the Cultural Socialization Scale based on retrospective
      reports from 208 young adults, maximizing young adults' ability to reason and
      reflect their adolescent experiences with various socialization practices. In the
      primary study, we examined the psychometric properties of the scale using reports
      from 252 adolescents. Cultural socialization occurred from both socialization
      agents toward both cultures. Our Cultural Socialization Scale demonstrated stable
      factor structures and high reliabilities. We observed strong factorial invariance
      across the 4 subscales (6 items). Multiple indicators multiple causes models also
      demonstrated invariance for each subscale across adolescents' demographic
      characteristics (i.e., gender, race/ethnicity, nativity, socioeconomic status,
      language of assessment). The implications of the Cultural Socialization Scale are
      discussed.

PMID- 25961140
TI  - Impact of a multicomponent screening, brief intervention, and referral to
      treatment (SBIRT) training curriculum on a medical residency program.
AB  - BACKGROUND: Substance-related disorders are a growing problem in the United
      States. The patient-provider setting can serve as a crucial environment to detect
      and prevent at-risk substance use. Screening, brief intervention, and referral to
      treatment (SBIRT) is an integrated approach to deliver early intervention and
      treatment services for persons who have or are at risk for substance-related
      disorders. SBIRT training components can include online modules, in-person
      instruction, practical experience, and clinical skills assessment. This paper
      will evaluate the impact of multiple modes of training on acquisition of SBIRT
      skills as observed in a clinical skills assessment. METHODS: Residents were part
      of an SBIRT training program, from 2009 through 2013, consisting of lecture, role
      play, online modules, patient encounters, and clinical skills assessment (CSA).
      Differences were assessed across satisfactory and unsatisfactory CSA performance.
      RESULTS: Seventy percent of the residents satisfactorily completed CSA.
      Demographics, type of components completed, and number of components completed
      were similar among residents who demonstrated satisfactory clinical skills
      compared with those who did not. All components of the training program were
      accepted equally across specialties and resident matriculation cohorts.
      CONCLUSION: The authors conclude that the components employed in SBIRT training
      do not have to be numerous or of a particular mode of training in order to see
      observable demonstration of SBIRT skills among medical residents. Thus, residency
      educators who have limited time or resources may utilize as few as 1 mode of
      training to effectually disseminate SBIRT skills among health care providers. As
      SBIRT continues to evolve as a promising tool to address at-risk substance
      related disorders, it is critical to train medical residents and other health
      professionals.

PMID- 25961142
TI  - Subpopulations of PKCgamma interneurons within the medullary dorsal horn revealed
      by electrophysiologic and morphologic approach.
AB  - Mechanical allodynia, a cardinal symptom of persistent pain, is associated with
      the unmasking of usually blocked local circuits within the superficial spinal or
      medullary dorsal horn (MDH) through which low-threshold mechanical inputs can
      gain access to the lamina I nociceptive output neurons. Specific interneurons
      located within inner lamina II (IIi) and expressing the gamma isoform of protein
      kinase C (PKCgamma+) have been shown to be key elements for such circuits.
      However, their morphologic and electrophysiologic features are still unknown.
      Using whole-cell patch-clamp recordings and immunohistochemical techniques in
      slices of adult rat MDH, we characterized such lamina IIi PKCgamma+ interneurons
      and compared them with neighboring PKCgamma- interneurons. Our results reveal
      that PKCgamma+ interneurons display very specific activity and response
      properties. Compared with PKCgamma- interneurons, they exhibit a smaller membrane
      input resistance and rheobase, leading to a lower threshold for action
      potentials. Consistently, more than half of PKCgamma+ interneurons respond with
      tonic firing to step current. They also receive a weaker excitatory synaptic
      drive. Most PKCgamma+ interneurons express Ih currents. The neurites of PKCgamma+
      interneurons arborize extensively within lamina IIi, can spread dorsally into
      lamina IIo, but never reach lamina I. In addition, at least 2 morphologically and
      functionally different subpopulations of PKCgamma+ interneurons can be
      identified: central and radial PKCgamma+ interneurons. The former exhibit a lower
      membrane input resistance, rheobase and, thus, action potential threshold, and
      less PKCgamma+ immunoreactivity than the latter. These 2 subpopulations might
      thus differently contribute to the gating of dorsally directed circuits within
      the MDH underlying mechanical allodynia.

PMID- 25961143
TI  - Distract or reappraise? Age-related differences in emotion-regulation choice.
AB  - Does aging impact strategy choice with regard to regulating negative emotions?
      Based on the assumption that older adults are highly motivated to quickly defuse
      negative states, we predicted that older adults, relative to young adults, would
      show an increased preference for distraction (a cognitive disengagement strategy)
      over reappraisal (a cognitive engagement strategy) in the face of negative
      material. A stronger preference for distraction, in turn, should be associated
      with higher affective well-being at older ages, as it helps to avoid high
      physiological arousal. Young (19-28 years, n = 38) and older (65-75 years, n =
      39) adults completed a laboratory task of emotion-regulation choice in which they
      viewed negative pictures of high and low intensity and chose between distraction
      and reappraisal to regulate their emotional response. Confirming predictions, age
      was associated with an increased preference to choose distraction over
      reappraisal. Among older but not young adults, the relative preference for
      distraction to reappraisal predicted higher state-affective well-being. In
      addition, across age groups, the preference for distraction over reappraisal was
      positively predicted by stimulus intensity and negatively by cognitive resources.
      Findings support the notion of an age-related shift toward disengagement
      strategies to regulate negative emotions, which maps onto older adults'
      prohedonic orientation and holds affective benefits.

PMID- 25961141
TI  - 8p deletion is strongly linked to poor prognosis in breast cancer.
AB  - Deletions of chromosome 8p occur frequently in breast cancers, but analyses of
      its clinical relevance have been limited to small patient cohorts and provided
      controversial results. A tissue microarray with 2,197 breast cancers was thus
      analyzed by fluorescence in-situ hybridization using an 8p21 probe in combination
      with a centromere 8 reference probe. 8p deletions were found in 50% of carcinomas
      with no special type, 67% of papillary, 28% of tubular, 37% of lobular cancers
      and 56% of cancers with medullary features. Deletions were always heterozygous.
      8p deletion was significantly linked to advanced tumor stage (P < 0.0001), high
      grade (P < 0.0001), high tumor cell proliferation (Ki67 Labeling Index; P <
      0.0001), and shortened overall survival (P < 0.0001). For example, 8p deletion
      was seen in 32% of 290 grade 1, 43% of 438 grade 2, and 65% of 427 grade 3
      cancers. In addition, 8p deletions were strongly linked to amplification of MYC
      (P < 0.0001), HER2 (P < 0.0001), and CCND1 (p = 0.001), but inversely associated
      with ER receptor expression (p = 0.0001). Remarkably, 46.5% of 8p-deleted cancers
      harbored amplification of at least one of the analyzed genes as compared to 27.5%
      amplifications in 8p-non-deleted cancers (P < 0.0001). In conclusion, 8p deletion
      characterizes a subset of particularly aggressive breast cancers. As 8p deletions
      are easy to analyze, this feature appears to be highly suited for future DNA
      based prognostic breast cancer panels. The strong link of 8p deletion with
      various gene amplifications raises the possibility of a role for regulating
      genomic stability. 

PMID- 25961145
TI  - End-of-treatment abstinence self-efficacy, behavioral processes of change, and
      posttreatment drinking outcomes in Project MATCH.
AB  - This study evaluated whether alcohol abstinence self-efficacy at the end of
      alcohol treatment was moderated by utilization of behavioral processes of change
      (coping activities used during a behavior change attempt). It was hypothesized
      that self-efficacy would be differentially important in predicting posttreatment
      drinking outcomes depending on the level of behavioral processes, such that the
      relation between self-efficacy and outcomes would be stronger for individuals who
      reported low process use. Analyses were also estimated with end-of-treatment
      abstinence included as a covariate. Data were analyzed from alcohol-dependent
      individuals in both treatment arms of Project MATCH (Matching Alcoholism
      Treatments to Client Heterogeneity; N = 1,328), a large alcohol treatment study.
      Self-efficacy was moderated by behavioral process use in predicting drinking
      frequency 6 and 12 months posttreatment and drinking quantity 6 months
      posttreatment such that self-efficacy was more strongly related to posttreatment
      drinking when low levels of processes were reported than high levels, but
      interactions were attenuated when end-of-treatment abstinence was controlled for.
      Significant quadratic relations between end-of-treatment self-efficacy and 6- and
      12-month posttreatment drinking quantity and frequency were found (p < .001, f2 =
      0.02-0.03), such that self-efficacy most robustly predicted outcomes when high.
      These effects remained significant when end-of-treatment abstinence was included
      as a covariate. Findings highlight the complex nature of self-efficacy's relation
      with drinking outcomes. Although the interaction between self-efficacy and
      behavioral processes was attenuated when end-of-treatment abstinence was
      controlled for, the quadratic effect of self-efficacy on outcomes remained
      significant. The pattern of these effects did not support the idea of
      "overconfidence" as a negative indicator.

PMID- 25961144
TI  - Do therapist behaviors differ with Hispanic youth? A brief look at within-session
      therapist behaviors and youth treatment response.
AB  - Brief addiction treatments, including motivational interviewing (MI), have shown
      promise with youth. One underexamined factor in this equation is the role of
      therapist behaviors. We therefore sought to assess whether and how therapist
      behaviors differ for Hispanic versus non-Hispanic youth and how that may be
      related to treatment outcome. With 80 substance-using adolescents (M age = 16
      years; 65% male; 59% Hispanic; 41% non-Hispanic), we examined the relationship
      between youth ethnicity and therapist behaviors across two brief treatments (MI
      and alcohol/marijuana education [AME]). We then explored relationships to youth 3
      month treatment response across four target outcomes: binge drinking days,
      alcohol-related problems, marijuana use days, and marijuana-related problems. In
      this study, therapists showed significantly more MI skills within the MI
      condition and more didactic skills in the AME condition. With respect to youth
      ethnicity, across both conditions (MI and AME), therapists used less MI skills
      with Hispanic youth. Contrary to expectations, therapists' use of MI skills was
      not connected to poorer outcomes for Hispanic youth across the board (e.g., for
      binge drinking days, marijuana use days, or marijuana-related problems). Rather,
      for Hispanic youth, therapists' use of lower MI skills was related only to poorer
      treatment outcomes in the context of alcohol-related problems. The observed
      relationships highlight the importance of investigating salient treatment
      interactions between therapist factors and youth ethnicity to guide improvements
      in youth treatment response.

PMID- 25961146
TI  - The influence of impulsiveness on binge eating and problem gambling: A
      prospective study of gender differences in Canadian adults.
AB  - This study investigated the degree to which facets of impulsiveness predicted
      future binge eating and problem gambling, 2 theorized forms of behavioral
      addiction. Participants were 596 women and 406 men from 4 age cohorts randomly
      recruited from a Canadian province. Participants completed self-report measures
      of 3 facets of impulsiveness (negative urgency, sensation seeking, lack of
      persistence), binge-eating frequency, and problem-gambling symptoms.
      Impulsiveness was assessed at baseline, and assessments of binge eating and
      problem gambling were followed up after 3 years. Weighted data were analyzed
      using zero-inflated negative binomial and Poisson regression models. We found
      evidence of transdiagnostic and disorder-specific predictors of binge eating and
      problem gambling. Negative urgency emerged as a common predictor of binge eating
      and problem gambling among women and men. There were disorder-specific
      personality traits identified among men only: High lack-of-persistence scores
      predicted binge eating and high sensation-seeking scores predicted problem
      gambling. Among women, younger age predicted binge eating and older age predicted
      problem gambling. Thus, there are gender differences in facets of impulsiveness
      that longitudinally predict binge eating and problem gambling, suggesting that
      treatments for these behaviors should consider gender-specific personality and
      demographic traits in addition to the common personality trait of negative
      urgency.

PMID- 25961147
TI  - The role of the working alliance in treatment for alcohol problems.
AB  - Little research has been done on the role of the therapeutic working alliance in
      treatment for alcohol problems. This longitudinal study's objectives were (a) to
      identify predictors of working alliance and (b) to investigate whether client
      and/or therapist reports of the working alliance predicted posttreatment
      motivation and then later treatment outcome. Client and therapist perceptions of
      the working alliance were assessed after the first treatment session using a
      short form of the Working Alliance Inventory (WAI) among 173 clients taking part
      in the United Kingdom Alcohol Treatment Trial (UKATT) and randomized to
      motivational enhancement therapy (MET) or social behavior and network therapy
      (SBNT) with complete data on all measures of interest. Structural equation models
      were fitted to identify predictors of WAI scores and investigate the
      relationships between WAI and measures of drinking during treatment,
      posttreatment motivation, and successful treatment outcome (abstinent or
      nonproblem drinker), and measures of drinks per drinking day and nondrinking
      days, assessed 9 months after the conclusion of treatment. Motivation to change
      drinking when treatment began was a strong predictor of client-adjusted
      coefficient = 2.21 (95% confidence interval [CI] [0.36, 4.06]-but not therapist
      WAI. Client WAI predicted successful treatment outcome-adjusted odds ratios (OR)
      = 1.09 (95% CI [1.02, 1.17])-and had effects on drinking during treatment, and on
      posttreatment motivation to change. There was evidence for effect modification by
      treatment, with strong associations between WAI and posttreatment motivation, and
      evidence of WAI prediction of treatment outcomes in the MET group, but no
      evidence of associations for SBNT. Therapist WAI was not strongly associated with
      treatment outcome (adjusted OR = 1.05; 95% CI [0.99, 1.10]). The working alliance
      is important to treatment outcomes for alcohol problems, with client evaluation
      of the alliance strongly related to motivation to change drinking throughout
      treatment for MET. It was also much more important than therapist-rated alliance
      in this study. (PsycINFO Database Record 

PMID- 25961148
TI  - Nonjudging facet of mindfulness predicts enhanced smoking cessation in Hispanics.
AB  - Although most smokers express interest in quitting, actual quit rates are low.
      Identifying strategies to enhance smoking cessation is critical, particularly
      among underserved populations, including Hispanics, for whom many of the leading
      causes of death are related to smoking. Mindfulness (purposeful, nonjudgmental
      attention to the present moment) has been linked to increased likelihood of
      cessation. Given that mindfulness is multifaceted, determining which aspects of
      mindfulness predict cessation could help to inform interventions. This study
      examined whether facets of mindfulness predict cessation in 199 Spanish-speaking
      smokers of Mexican heritage (63.3% male, mean age of 39 years, 77.9% with a high
      school education or less) receiving smoking cessation treatment. Primary outcomes
      were 7-day abstinence at weeks 3 and 26 postquit (biochemically confirmed and
      determined using an intent-to-treat approach). Logistic random coefficient
      regression models were utilized to examine the relationship between mindfulness
      facets and abstinence over time. Independent variables were subscales of the Five
      Facet Mindfulness Questionnaire (Observing, Describing, Acting With Awareness,
      Nonjudging, and Nonreactivity). The Nonjudging subscale (i.e., accepting thoughts
      and feelings without evaluating them) uniquely predicted better odds of
      abstinence up to 26 weeks postquit. This is the first known study to examine
      whether specific facets of mindfulness predict smoking cessation. The ability to
      experience thoughts, emotions, and withdrawal symptoms without judging them may
      be critical in the process of quitting smoking. Results indicate potential
      benefits of mindfulness among smokers of Mexican heritage and suggest that
      smoking cessation interventions might be enhanced by central focus on the
      Nonjudging aspect of mindfulness.

PMID- 25961149
TI  - The magnitude of drug attentional bias is specific to substance use disorder.
AB  - The visual probe task with eye tracking is a sensitive measure of cocaine and
      alcohol cue attentional bias. Despite the high comorbidity between cocaine and
      alcohol dependence, attentional bias studies have examined the influence of
      cocaine- and alcohol-related cues separately. The aim of this experiment was to
      directly compare the magnitude of cocaine and alcohol cue attentional bias in
      individuals dependent on cocaine or cocaine and alcohol. Individuals who met
      criteria for cocaine dependence (n = 20) or both cocaine and alcohol dependence
      (n = 20) completed a visual probe task with eye tracking. Cocaine-dependent
      participants displayed an attentional bias toward cocaine, but not alcohol. In
      contrast, cocaine-alcohol dependent participants displayed an attentional bias to
      both cocaine and alcohol, and the magnitude of these biases did not differ. The
      magnitude of cocaine cue attentional bias, however, was significantly smaller in
      the cocaine-alcohol dependent group compared to the cocaine-dependent group.
      These results suggest that fixation time during the visual probe task is
      sensitive to clinically relevant differences in substance use disorders. The
      incentive value of cocaine-related cues, however, may differ for individuals who
      are also dependent on alcohol.

PMID- 25961150
TI  - High gain hybrid graphene-organic semiconductor phototransistors.
AB  - Hybrid phototransistors of graphene and the organic semiconductor poly(3
      hexylthiophene-2,5-diyl) (P3HT) are presented. Two types of phototransistors are
      demonstrated with a charge carrier transit time that differs by more than 6
      orders of magnitude. High transit time devices are fabricated using a photoresist
      free recipe to create large-area graphene transistors made out of graphene grown
      by chemical vapor deposition. Low transit time devices are fabricated out of
      mechanically exfoliated graphene on top of mechanically exfoliated hexagonal
      boron nitride using standard e-beam lithography. Responsivities exceeding 10(5)
      A/W are obtained for the low transit time devices. 

PMID- 25961152
TI  - Osteogenic embryoid body-derived material induces bone formation in vivo.
AB  - The progressive loss of endogenous regenerative capacity that accompanies
      mammalian aging has been attributed at least in part to alterations in the
      extracellular matrix (ECM) composition of adult tissues. Thus, creation of a more
      regenerative microenvironment, analogous to embryonic morphogenesis, may be
      achieved via pluripotent embryonic stem cell (ESC) differentiation and derivation
      of devitalized materials as an alternative to decellularized adult tissues, such
      as demineralized bone matrix (DBM). Transplantation of devitalized ESC materials
      represents a novel approach to promote functional tissue regeneration and reduce
      the inherent batch-to-batch variability of allograft-derived materials. In this
      study, the osteoinductivity of embryoid body-derived material (EBM) was compared
      to DBM in a standard in vivo ectopic osteoinduction assay in nude mice. EBM
      derived from EBs differentiated for 10 days with osteogenic media (+beta
      glycerophosphate) exhibited similar osteoinductivity to active DBM
      (osteoinduction score = 2.50 +/- 0.27 vs. 2.75 +/- 0.16) based on histological
      scoring, and exceeded inactive DBM (1.13 +/- 0.13, p < 0.005). Moreover, EBM
      stimulated formation of new bone, ossicles, and marrow spaces, similar to active
      DBM. The potent osteoinductivity of EBM demonstrates that morphogenic factors
      expressed by ESCs undergoing osteogenic differentiation yield a novel devitalized
      material capable of stimulating de novo bone formation in vivo. 

PMID- 25961154
TI  - Experimental (X-ray, (13)C CP/MAS NMR, IR, RS, INS, THz) and Solid-State DFT
      Study on (1:1) Co-Crystal of Bromanilic Acid and 2,6-Dimethylpyrazine.
AB  - A combined structural, vibrational spectroscopy, and solid-state DFT study of the
      hydrogen-bonded complex of bromanilic acid with 2,6-dimethylpyrazine is reported.
      The crystallographic structure was determined by means of low-temperature single
      crystal X-ray diffraction, which reveals the molecular units in their native
      protonation states, forming one-dimensional infinite nets of moderate-strength
      O...H-N hydrogen bonds. The nature of the crystallographic forces, stabilizing
      the studied structure, has been drawn by employing the noncovalent interactions
      analysis. It was found that, in addition to the hydrogen bonding, the
      intermolecular forces are dominated by stacking interactions and C-H...O
      contacts. The thermal and calorimetric analysis was employed to probe stability
      of the crystal phase. The structural analysis was further supported by a
      computationally assisted (13)C CP/MAS NMR study, providing a complete assignment
      of the recorded resonances. The vibrational dynamics was explored by combining
      the optical (IR, Raman, TDs-THz) and inelastic neutron scattering (INS)
      spectroscopy techniques with the state-of-the-art solid-state density functional
      theory (DFT) computations. Despite the quasi-harmonic approximation assumed
      throughout the study, an excellent agreement between the theoretical and
      experimental data was achieved over the entire spectral range, allowing for a
      deep and possibly thorough understanding of the vibrational characteristics of
      the system. Particularly, the significant influence of the long-range dipole
      coupling on the IR spectrum has been revealed. On the basis of a wealth of
      information gathered, the recent implementation of a dispersion-corrected linear
      response scheme has been extensively examined. 

PMID- 25961153
TI  - The emerging role of CaMKII in cancer.
AB  - Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a multifunctional
      serine/threonine kinases best known for its critical role in learning and memory.
      Recent studies suggested that high levels of CaMKII also expressed in variety of
      malignant diseases. In this review, we focus on the structure and biology
      properties of CaMKII, including the role of CaMKII in the regulation of cancer
      progression and therapy response. We also describe the role of CaMKII in the
      diagnosis of different kinds of cancer and recent progress in the development of
      CaMKII inhibitors. These data establishes CaMKII as a novel target whose
      modulation presents new opportunities for cancer diagnosis and treatment. 

PMID- 25961155
TI  - Controllable fabrication of copper phthalocyanine nanostructure crystals.
AB  - Copper phthalocyanine (CuPc) nanostructure crystals, including nanoflower,
      nanoribbon, and nanowire, were controllably fabricated by temperature gradient
      physical vapor deposition (TG-PVD) through controlling the growth parameters. In
      a controllable growth system with carrier gas N2, nanoflower, nanoribbon, and
      nanowire crystals were formed in a high-temperature zone, medium-temperature
      zone, and low-temperature zone, respectively. They were proved to be beta-phase,
      coexist of alpha-phase and beta-phase, and alpha-phase respectively based on x
      ray diffraction results. Furthermore, ultralong CuPc nanowires up to several
      millimeters could be fabricated by TG-PVD without carrier gas, and they were well
      aligned to form large-area CuPc nanowire crystal arrays by the Langmuir-Blodgett
      method. The nanostructure crystals showed unusual optical absorption spectra from
      the ultraviolet-visible to near-infrared range, which was explained by the
      diffraction and scattering caused by the wavelength-sized nanostructures. These
      CuPc nanostructure crystals show potential applications in organic electronic and
      optoelectronic devices. 

PMID- 25961156
TI  - Return to Learning After a Concussion and Compliance With Recommendations for
      Cognitive Rest.
AB  - OBJECTIVE: To determine the compliance of schools and school nurses in the United
      States with national recommendations for cognitive rest in students who sustain a
      concussion. DESIGN: Cross-sectional questionnaire based. PARTICIPANTS: Members of
      the National Association of School Nurses working at the high school level.
      INTERVENTION: A questionnaire, developed by the authors and based on
      recommendations for cognitive rest, was electronically distributed 3 times during
      the 2012 to 2013 academic year. MAIN OUTCOME MEASURES: Self-reported responses
      were collected regarding demographics and compliance of schools and school nurses
      with recommendations for the management of the postconcussion student, including
      the presence of specific guidelines for individualized care and the
      responsibility of the nurse for the prevention, detection, and management of
      concussions. RESULTS: Analysis was performed on 1033 completed questionnaires
      (36% usable response rate). Fifty-three percent of schools have guidelines to
      assist students when returning to school after a concussion. These guidelines
      include extension of assignment deadlines (87%), rest periods during the school
      day (84%), postponement or staggering of tests (75%), reduced workload (73%), and
      accommodation for light or noise sensitivity (64%). Sixty-six percent of nurses
      in our sample have had special training in the recognition and management of
      concussions. Nurses reported involvement in the following roles: identifying
      suspected concussions (80%), providing emotional support for recovering students
      dealing with concussion-related depression (59%), and guiding the student's
      postconcussion graduated academic and activity re-entry process (58%).
      CONCLUSIONS: We detected a wide variability in compliance of schools and school
      nurses with national recommendations for cognitive rest. CLINICAL RELEVANCE:
      Ensuring that schools have policies established for a student's return to
      learning, having specific guidelines to provide an individualized approach to
      return to learning based on postconcussion signs/symptoms, training school nurses
      in the recognition and management of concussions, and involving school nurses in
      the re-entry process are identified areas for improvement. Schools in the United
      States should be aware of these recommendations to guide a student's
      postconcussion graduated academic re-entry process.

PMID- 25961157
TI  - Gender Differences in Plantar Loading During an Unanticipated Side Cut on
      FieldTurf.
AB  - OBJECTIVE: To determine whether force-time integral (FTI) and maximum force (MF)
      are significantly different between genders when performing an unanticipated side
      cut on FieldTurf. DESIGN: Thirty-two collegiate athletes (16 men and 16 women)
      completed 12 unanticipated cutting trials, while plantar pressure data were
      recorded using Pedar-X insoles. SETTING: Controlled Laboratory Study.
      PARTICIPANTS: Division I cleated sport athletes with no previous foot and ankle
      surgery, no history of lower extremity injury in the past 6 months, and no
      history of metatarsal stress fracture. INTERVENTIONS: None. MAIN OUTCOME
      MEASURES: Maximum force and the FTI in the total foot, medial midfoot (MMF),
      lateral midfoot (LMF), medial forefoot (MFF), middle forefoot (MiddFF), and the
      lateral forefoot (LFF). RESULTS: Males had a greater FTI beneath the entire foot
      (TF) (P < 0.001). Females had a significantly higher MF beneath the LMF (P =
      0.001), MiddFF (P < 0.001), and LFF (P = 0.001). Males had a significantly
      greater MF beneath the MMF (P = 0.003) and greater FTI beneath the MMF (P <
      0.001) and MFF (P = 0.002). CONCLUSIONS: Significant differences in plantar
      loading exist between genders with males demonstrating increased loading beneath
      the TF in comparison with females. Females had overall greater loading on the
      lateral column, whereas males had greater loading on the medial column of the
      foot. CLINICAL RELEVANCE: The results of this study indicate that plantar loading
      is different between genders; therefore, altering cleated footwear to be gender
      specific may result in more optimal foot loading patterns. Optimizing cleated
      shoe design could decrease the risk for metatarsal stress fractures.

PMID- 25961158
TI  - Superficial Vein Thrombophlebitis in a Football Athlete.
AB  - A 22-year-old professional football player presented to a preparticipation
      physical examination with a 2-week history of left leg discomfort extending from
      the groin to the knee over the previous 2 weeks. He was found to have superficial
      vein thrombophlebitis (SVT) of the left great saphenous vein extending from the
      knee to within approximately 1.6 cm of the saphenofemoral junction. There is
      paucity in the literature regarding the management of SVT, particularly in
      actively training athletes. This case addresses the considerations of
      anticoagulation management for SVT as well as the unique challenge of managing
      anticoagulation therapy in an athlete that is actively training. 

PMID- 25961159
TI  - Antitrypanosomal Acetylene Fatty Acid Derivatives from the Seeds of Porcelia
      macrocarpa (Annonaceae).
AB  - Chagas' disease is caused by a parasitic protozoan and affects the poorest
      population in the world, causing high mortality and morbidity. As a result of the
      toxicity and long duration of current treatments, the discovery of novel and more
      efficacious drugs is crucial. In this work, the hexane extract from seeds of
      Porcelia macrocarpa R.E. Fries (Annonaceae) displayed in vitro antitrypanosomal
      activity against trypomastigote forms of T. cruzi by the colorimetric MTT assay
      (IC50 of 65.44 MUg/mL). Using chromatographic fractionation over SiO2, this
      extract afforded a fraction composed by one active compound (IC50 of 10.70
      ug/mL), which was chemically characterized as 12,14-octadecadiynoic acid
      (macrocarpic acid). Additionally, two new inactive acetylene compounds
      (alpha,alpha'-dimacro-carpoyl-beta-oleylglycerol and alpha-macrocarpoyl-alpha'
      oleylglycerol) were also isolated from the hexane extract. The complete
      characterization of the isolated compounds was performed by analysis of NMR and
      MS data as well as preparation of derivatives. 

PMID- 25961160
TI  - Novel all trans-retinoic Acid derivatives: cytotoxicity, inhibition of cell cycle
      progression and induction of apoptosis in human cancer cell lines.
AB  - Owing to the pharmacological potential of ATRA (all trans-retinoic acid), a
      series of retinamides and a 1-(retinoyl)-1,3-dicyclohexylurea compound were
      prepared by reacting ATRA with long chain alkyl or alkenyl fatty amines by using
      a 4-demethylaminopyridine (DMAP)-catalyzed N,Nc-dicyclohexylcarbodiimide (DCC)
      coupling. The successful synthesis of the target compounds was demonstrated using
      a range of spectroscopic techniques. The cytotoxicity of the compounds was
      measured along with their ability to induce cell cycle arrest and apoptosis in
      human cancer cell lines MCF-7 (breast cancer) and HepG2 (liver cancer) and normal
      human cell line HEK293 (embryonic kidney). The results of cytotoxicity and flow
      cytometry data showed that the compounds had a moderate to strong effect against
      MCF-7 and HepG2 cells and were less toxic to HEK293 cells. N-oleyl-retinamide was
      found to be the most potent anticancer agent and was more effective against MCF-7
      cells than HepG2 cells. 

PMID- 25961161
TI  - Antiproliferative Activity of Hinokitiol, a Tropolone Derivative, Is Mediated via
      the Inductions of p-JNK and p-PLCgamma1 Signaling in PDGF-BB-Stimulated Vascular
      Smooth Muscle Cells.
AB  - Abnormal proliferation of vascular smooth muscle cells (VSMCs) is important in
      the pathogenesis of vascular disorders such as atherosclerosis and restenosis.
      Hinokitiol, a tropolone derivative found in Chamacyparis taiwanensis, has been
      found to exhibit anticancer activity in a variety of cancers through inhibition
      of cell proliferation. In the present study, the possible anti-proliferative
      effect of hinokitiol was investigated on VSMCs. Our results showed that
      hinokitiol significantly attenuated the PDGF-BB-stimulated proliferation of VSMCs
      without cytotoxicity. Hinokitiol suppressed the expression of proliferating cell
      nuclear antigen (PCNA), a maker for cell cycle arrest, and caused G0/G1 phase
      arrest in cell cycle progression. To investigate the mechanism underlying the
      anti-proliferative effect of hinokitiol, we examined the effects of hinokitiol on
      phosphorylations of Akt, ERK1/2, p38 and JNK1/2. Phospholipase C (PLC)-gamma1
      phosphorylation, its phosphorylated substrates and p27kip1 expression was also
      analyzed. Pre-treatment of VSMCs with hinikitiol was found to significantly
      inhibit the PDGF-BB-induced phosphorylations of JNK1/2 and PLC-gamma1, however no
      effects on Akt, ERK1/2, and p38. The up-regulation of p27kip1 was also observed
      in hinokitiol-treated VSMCs. Taken together, our results suggest that hinokitiol
      inhibits PDGF-BB-induced proliferation of VSMCs by inducing cell cycle arrest,
      suppressing JNK1/2 phosphorylation and PLC-gamma1, and stimulating p27kip1
      expression. These findings suggest that hinokitiol may be beneficial for the
      treatment of vascular-related disorders and diseases. 

PMID- 25961162
TI  - A facile and mild synthesis of trisubstituted allylic sulfones from Morita-Baylis
      Hillman carbonates.
AB  - An efficient and catalyst-free synthesis of trisubstituted allylic sulfones
      through an allylic sulfonylation reaction of Morita-Baylis-Hillman (MBH)
      carbonates with sodium sulfinates has been developed. Under the optimized
      reaction conditions, a series of trisubstituted allylic sulfones were rapidly
      prepared in good to excellent yields (71%-99%) with good to high selectivity (Z/E
      from 79:21 to >99:1). Compared with known synthetic methods, the current protocol
      features mild reaction temperature, high efficiency and easily available
      reagents. 

PMID- 25961163
TI  - Synthesis, molecular structure and spectroscopic investigations of novel
      fluorinated spiro heterocycles.
AB  - This paper describes an efficient and regioselective method for the synthesis of
      novel fluorinated spiro-heterocycles in excellent yield by cascade [5+1] double
      Michael addition reactions. The compounds 7,11-bis(4-fluorophenyl)-2,4-dimethyl-
      2,4-diazaspiro[5.5] undecane-1,3,5,9-tetraone (3a) and 2,4-dimethyl-7,11-bis (4
      (trifluoromethyl)phenyl)-2,4-diazaspiro[5.5]undecane-1,3,5,9-tetraone (3b) were
      characterized by single-crystal X-ray diffraction, FT-IR and NMR techniques. The
      optimized geometrical parameters, infrared vibrational frequencies and NMR
      chemical shifts of the studied compounds have also been calculated using the
      density functional theory (DFT) method, using Becke-3-Lee-Yang-Parr functional
      and the 6-311G(d,p) basis set. There is good agreement between the experimentally
      determined structural parameters, vibrational frequencies and NMR chemical shifts
      of the studied compounds and those predicted theoretically. The calculated
      natural atomic charges using NBO method showed higher polarity of 3a compared to
      3b.The calculated electronic spectra are also discussed based on the TD-DFT
      calculations. 

PMID- 25961164
TI  - Celastrol Protects against Antimycin A-Induced Insulin Resistance in Human
      Skeletal Muscle Cells.
AB  - Mitochondrial dysfunction and inflammation are widely accepted as key hallmarks
      of obesity-induced skeletal muscle insulin resistance. The aim of the present
      study was to evaluate the functional roles of an anti-inflammatory compound,
      celastrol, in mitochondrial dysfunction and insulin resistance induced by
      antimycin A (AMA) in human skeletal muscle cells. We found that celastrol
      treatment improved insulin-stimulated glucose uptake activity of AMA-treated
      cells, apparently via PI3K/Akt pathways, with significant enhancement of
      mitochondrial activities. Furthermore, celastrol prevented increased levels of
      cellular oxidative damage where the production of several pro-inflammatory
      cytokines in cultures cells was greatly reduced. Celastrol significantly
      increased protein phosphorylation of insulin signaling cascades with amplified
      expression of AMPK protein and attenuated NF-kappaB and PKC theta activation in
      human skeletal muscle treated with AMA. The improvement of insulin signaling
      pathways by celastrol was also accompanied by augmented GLUT4 protein expression.
      Taken together, these results suggest that celastrol may be advocated for use as
      a potential therapeutic molecule to protect against mitochondrial dysfunction
      induced insulin resistance in human skeletal muscle cells. 

PMID- 25961165
TI  - Prediction of placental barrier permeability: a model based on partial least
      squares variable selection procedure.
AB  - Assessing the human placental barrier permeability of drugs is very important to
      guarantee drug safety during pregnancy. Quantitative structure-activity
      relationship (QSAR) method was used as an effective assessing tool for the
      placental transfer study of drugs, while in vitro human placental perfusion is
      the most widely used method. In this study, the partial least squares (PLS)
      variable selection and modeling procedure was used to pick out optimal
      descriptors from a pool of 620 descriptors of 65 compounds and to simultaneously
      develop a QSAR model between the descriptors and the placental barrier
      permeability expressed by the clearance indices (CI). The model was subjected to
      internal validation by cross-validation and y-randomization and to external
      validation by predicting CI values of 19 compounds. It was shown that the model
      developed is robust and has a good predictive potential (r2=0.9064, RMSE=0.09,
      q2=0.7323, rp2=0.7656, RMSP=0.14). The mechanistic interpretation of the final
      model was given by the high variable importance in projection values of
      descriptors. Using PLS procedure, we can rapidly and effectively select optimal
      descriptors and thus construct a model with good stability and predictability.
      This analysis can provide an effective tool for the high-throughput screening of
      the placental barrier permeability of drugs.

PMID- 25961151
TI  - Rare and Coding Region Genetic Variants Associated With Risk of Ischemic Stroke:
      The NHLBI Exome Sequence Project.
AB  - IMPORTANCE: Stroke is the second leading cause of death and the third leading
      cause of years of life lost. Genetic factors contribute to stroke prevalence, and
      candidate gene and genome-wide association studies (GWAS) have identified
      variants associated with ischemic stroke risk. These variants often have small
      effects without obvious biological significance. Exome sequencing may discover
      predicted protein-altering variants with a potentially large effect on ischemic
      stroke risk. OBJECTIVE: To investigate the contribution of rare and common
      genetic variants to ischemic stroke risk by targeting the protein-coding regions
      of the human genome. DESIGN, SETTING, AND PARTICIPANTS: The National Heart, Lung,
      and Blood Institute (NHLBI) Exome Sequencing Project (ESP) analyzed approximately
      6000 participants from numerous cohorts of European and African ancestry. For
      discovery, 365 cases of ischemic stroke (small-vessel and large-vessel subtypes)
      and 809 European ancestry controls were sequenced; for replication, 47 affected
      sibpairs concordant for stroke subtype and an African American case-control
      series were sequenced, with 1672 cases and 4509 European ancestry controls
      genotyped. The ESP's exome sequencing and genotyping started on January 1, 2010,
      and continued through June 30, 2012. Analyses were conducted on the full data set
      between July 12, 2012, and July 13, 2013. MAIN OUTCOMES AND MEASURES: Discovery
      of new variants or genes contributing to ischemic stroke risk and subtype
      (primary analysis) and determination of support for protein-coding variants
      contributing to risk in previously published candidate genes (secondary
      analysis). RESULTS: We identified 2 novel genes associated with an increased risk
      of ischemic stroke: a protein-coding variant in PDE4DIP (rs1778155; odds ratio,
      2.15; P = 2.63 * 10(-8)) with an intracellular signal transduction mechanism and
      in ACOT4 (rs35724886; odds ratio, 2.04; P = 1.24 * 10(-7)) with a fatty acid
      metabolism; confirmation of PDE4DIP was observed in affected sibpair families
      with large-vessel stroke subtype and in African Americans. Replication of protein
      coding variants in candidate genes was observed for 2 previously reported GWAS
      associations: ZFHX3 (cardioembolic stroke) and ABCA1 (large-vessel stroke).
      CONCLUSIONS AND RELEVANCE: Exome sequencing discovered 2 novel genes and
      mechanisms, PDE4DIP and ACOT4, associated with increased risk for ischemic
      stroke. In addition, ZFHX3 and ABCA1 were discovered to have protein-coding
      variants associated with ischemic stroke. These results suggest that genetic
      variation in novel pathways contributes to ischemic stroke risk and serves as a
      target for prediction, prevention, and therapy.

PMID- 25961166
TI  - Variety and Harvesting Season Effects on Antioxidant Activity and Vitamins
      Content of Citrus sinensis Macfad.
AB  - Five sweet orange (Citrus sinensis Osbeck) varieties cultivated in Huelva (Spain)
      and picked at two seasons during two consecutive years, were characterized for
      their antioxidant activity (free radicals scavenging activity, reducing power and
      lipid peroxidation inhibition) and vitamin content (vitamin E and vitamin C). The
      effects induced by sweet orange variety and stage of maturity were
      comprehensively compared by applying 2-way ANOVA and linear discriminant
      analysis. The results indicated higher differences in antioxidant activity and
      vitamin contents in response to the effect of the harvesting season, when
      compared to the effect of sweet orange variety. Nevertheless, the results
      observed in 2012 showed less marked differences among the assayed sweet orange
      varieties. Either way, it might be concluded that oranges sampled in January show
      the highest antioxidant activity and vitamin contents. Furthermore, concerning
      the properties evaluated in this work, all sweet orange varieties represent good
      alternatives, except for Rhode Summer, which would not be the preferable choice
      as a target to enhance sweet orange overall characteristics. 

PMID- 25961167
TI  - Correction: Chigrinova, M., et al. Kinugasa reactions in water: from green
      chemistry to bioorthogonal labelling. Molecules 2015, 20, 6959-6969.
AB  - The authors wish to make the following correction to this paper [1]: The author
      name "Paul Pezacki" should be "John Paul Pezacki". [...]. 

PMID- 25961168
TI  - Influence of torsional strength on different types of dental implant platforms.
AB  - AIM: The study assessed deformation of implant components submitted to torsion
      tests of 80 and 120 N . cm using an optical stereomicroscope. MATERIAL AND
      METHODS: The following 3 types of Titaniumfix conical implant connections (n = 5)
      measuring O 4.0 * 11.5 mm were used: external, internal hexagon and Morse taper
      connections. The diagonal and lateral measurements of the hexagon implant
      platform were measured before and after the torsion test. RESULTS: The torsion
      test using torque of 80 and 120 N . cm altered the implant dental platforms. All
      groups presented deformation of implant component after torque of 80 N . cm with
      no statistical difference among them. During torque of 120 N . cm, a difference
      in the Morse taper connection in relation to the internal and external hexagon
      connection was observed. The Morse taper connection implant, followed by the
      internal hex implant, underwent less deformation. Greater deformation occurred in
      the external hex implants. CONCLUSION: For all the implants, high insertion
      torques deformed the implant platform preventing long-term maintenance and
      stability of implants.

PMID- 25961169
TI  - Crystal Structures of mPGES-1 Inhibitor Complexes Form a Basis for the Rational
      Design of Potent Analgesic and Anti-Inflammatory Therapeutics.
AB  - Microsomal prostaglandin E synthase 1 (mPGES-1) is an alpha-helical homotrimeric
      integral membrane inducible enzyme that catalyzes the formation of prostaglandin
      E2 (PGE2) from prostaglandin H2 (PGH2). Inhibition of mPGES-1 has been proposed
      as a therapeutic strategy for the treatment of pain, inflammation, and some
      cancers. Interest in mPGES-1 inhibition can, in part, be attributed to the
      potential circumvention of cardiovascular risks associated with anti-inflammatory
      cyclooxygenase 2 inhibitors (coxibs) by targeting the prostaglandin pathway
      downstream of PGH2 synthesis and avoiding suppression of antithrombotic
      prostacyclin production. We determined the crystal structure of mPGES-1 bound to
      four potent inhibitors in order to understand their structure-activity
      relationships and provide a framework for the rational design of improved
      molecules. In addition, we developed a light-scattering-based thermal stability
      assay to identify molecules for crystallographic studies. 

PMID- 25961170
TI  - A hydrogel-endothelial cell implant mimics infantile hemangioma: modulation by
      survivin and the Hippo pathway.
AB  - Microvascular endothelial cells cultured in three-dimensional hydrogel scaffolds
      form a network of microvessel structures when implanted subcutaneously in mice,
      inosculate with host vessels, and over time remodel into large ectatic vascular
      structures resembling hemangiomas. When compared with infantile hemangiomas,
      similarities were noted, including a temporal progression from a morphological
      appearance of a proliferative phase to the appearance of an involuted phase,
      mimicking the proliferative and involutional phases of infantile hemangioma.
      Consistent with the progression of a proliferative phase to an involuted phase,
      both the murine implants and human biopsy tissue exhibit reduced expression of
      Ajuba, YAP, and Survivin labeling as they progressed over time. Significant
      numbers of CD45+, CD11b+, Mac3+ mononuclear cells were found at the 2-week time
      point in our implant model that correlated with the presence of CD45+, CD68+
      mononuclear cells observed in biopsies of human proliferative-phase hemangiomas.
      At the 4-week time point in our implant model, only small numbers of CD45+ cells
      were detected, which again correlated with our findings of significantly
      diminished CD45+, CD68+ mononuclear cells in human involutional-phase
      hemangiomas. The demonstration of mononuclear cell infiltration transiently in
      the proliferative phase of these lesions suggests that the vascular proliferation
      and/or regression may be driven in part by an immune response. Gross and
      microscopic morphological appearances of human proliferative and involutional
      hemangiomas and our implant model correlate well with each other as do the
      expression levels of Hippo pathway components (Ajuba and YAP) and Survivin and
      correlate with proliferation in these entities. Inhibitors of Survivin and Ajuba
      (which we have demonstrated to inhibit proliferation and increase apoptosis in
      murine hemangioendothelioma cell tissue culture) may have potential as other
      beneficial treatments for proliferating infantile hemangiomas. This implant model
      may have potential as a modest through-put screen for testing and development of
      therapeutics targeted at the proliferative phase of infantile hemangiomas,
      reducing the subsequent postinvolutional scarring or deformities sometimes
      associated with these lesions. 

PMID- 25961172
TI  - Tuberculoid reaction to a cosmetic tattoo on the lips.

PMID- 25961175
TI  - Clinical and pathological features of mitochondrial DNA deletion disease
      following antiretroviral treatment.

PMID- 25961171
TI  - MicroRNA-129-5p modulates epithelial-to-mesenchymal transition by targeting SIP1
      and SOX4 during peritoneal dialysis.
AB  - Peritoneal dialysis (PD) is the most readily feasible home-dialysis method for
      renal replacement therapy. However, repeated use of PD can lead to induction of
      mesothelial/epithelial-mesenchymal transition (MMT/EMT) and fibrosis, eventually
      leading to ultrafiltration failure and discontinuation of PD. MicroRNA-129-5p
      (miR-129-5p) is believed to be a potent downstream inhibitor of TGF-beta1 in
      renal fibrosis, but the effect of miR-129-5p on MMT/EMT relevant to PD is
      unknown. In this study, as determined by microRNA array analysis and confirmed by
      northern blot analysis and real-time PCR, we demonstrate that miRNA-129-5p is
      decreased in mesothelial cells isolated from effluent of patients having PD for
      more than 6 months extending to several years compared with those who have
      undergone PD for less than 6 months. The decreased expression of miR-129-5p was
      accompanied with alterations in EMT-related genes and the expression of
      respective proteins in vivo. In addition, in in vitro studies we noted that the
      expression of E-cadherin and claudin-1 were significantly reduced with increased
      cell migration in HMrSV5, a human peritoneal mesothelial cell line (HPMC),
      treated with TGF-beta1, whereas expression of vimentin, fibronectin and
      transcription factors SIP1 and SOX4 increased significantly, as assessed by real
      time PCR, western blot analysis and immunofluorescence microscopy. Furthermore,
      alteration in EMT-related genes and proteins were reversed by overexpression of
      miR-129-5p. No effect was observed in cells treated with miR-negative control.
      Meanwhile, inhibition of SIP1 and SOX4 with their respective siRNA also could
      decrease the expression of EMT-related genes and protein levels in HPMCs induced
      with TGF-beta1. Finally, we demonstrate that SIP1 can inhibit the promoter
      activity of E-cadherin while enhancing the promoter activity of vimentin. We also
      observed that miR-129-5p could directly target the 3'UTR of SIP1 and SOX4 genes,
      and repressed their post-transcriptional activities. These data suggest that
      there is a novel TGF-beta1/miR-129-5p/SIP-1 or SOX4 pathway that has a
      significant role in MMT and fibrosis in the setting of PD. 

PMID- 25961176
TI  - Association between vaccines and neuroinflammation: time, risks, and benefits.

PMID- 25961177
TI  - Association between vaccines and neuroinflammation-reply.

PMID- 25961178
TI  - Defining the Eye-of-the-Tiger Sign.

PMID- 25961179
TI  - Defining the Eye-of-the-Tiger Sign-Reply.

PMID- 25961180
TI  - Statin use during hospitalization for intracerebral hemorrhage.

PMID- 25961182
TI  - Error in figure legend.

PMID- 25961181
TI  - Statin use during hospitalization for intracerebral hemorrhage-reply.

PMID- 25961183
TI  - Typographical errors in figure.

PMID- 25961184
TI  - Mediterranean Diet and Age-Related Cognitive Decline: A Randomized Clinical
      Trial.
AB  - IMPORTANCE: Oxidative stress and vascular impairment are believed to partly
      mediate age-related cognitive decline, a strong risk factor for development of
      dementia. Epidemiologic studies suggest that a Mediterranean diet, an antioxidant
      rich cardioprotective dietary pattern, delays cognitive decline, but clinical
      trial evidence is lacking. OBJECTIVE: To investigate whether a Mediterranean diet
      supplemented with antioxidant-rich foods influences cognitive function compared
      with a control diet. DESIGN, SETTING, AND PARTICIPANTS: Parallel-group randomized
      clinical trial of 447 cognitively healthy volunteers from Barcelona, Spain (233
      women [52.1%]; mean age, 66.9 years), at high cardiovascular risk were enrolled
      into the Prevencion con Dieta Mediterranea nutrition intervention trial from
      October 1, 2003, through December 31, 2009. All patients underwent
      neuropsychological assessment at inclusion and were offered retesting at the end
      of the study. INTERVENTIONS: Participants were randomly assigned to a
      Mediterranean diet supplemented with extravirgin olive oil (1 L/wk), a
      Mediterranean diet supplemented with mixed nuts (30 g/d), or a control diet
      (advice to reduce dietary fat). MAIN OUTCOMES AND MEASURES: Rates of cognitive
      change over time based on a neuropsychological test battery: Mini-Mental State
      Examination, Rey Auditory Verbal Learning Test (RAVLT), Animals Semantic Fluency,
      Digit Span subtest from the Wechsler Adult Intelligence Scale, Verbal Paired
      Associates from the Wechsler Memory Scale, and the Color Trail Test. We used mean
      z scores of change in each test to construct 3 cognitive composites: memory,
      frontal (attention and executive function), and global. RESULTS: Follow-up
      cognitive tests were available in 334 participants after intervention (median,
      4.1 years). In multivariate analyses adjusted for confounders, participants
      allocated to a Mediterranean diet plus olive oil scored better on the RAVLT (P =
      .049) and Color Trail Test part 2 (P = .04) compared with controls; no between
      group differences were observed for the other cognitive tests. Similarly adjusted
      cognitive composites (mean z scores with 95% CIs) for changes above baseline of
      the memory composite were 0.04 (-0.09 to 0.18) for the Mediterranean diet plus
      olive oil, 0.09 (-0.05 to 0.23; P = .04 vs controls) for the Mediterranean diet
      plus nuts, and -0.17 (-0.32 to -0.01) for the control diet. Respective changes
      from baseline of the frontal cognition composite were 0.23 (0.03 to 0.43; P =
      .003 vs controls), 0.03 (-0.25 to 0.31), and -0.33 (-0.57 to -0.09). Changes from
      baseline of the global cognition composite were 0.05 (-0.11 to 0.21; P = .005 vs
      controls) for the Mediterranean diet plus olive oil, -0.05 (-0.27 to 0.18) for
      the Mediterranean diet plus nuts, and -0.38 (-0.57 to -0.18) for the control
      diet. All cognitive composites significantly (P < .05) decreased from baseline in
      controls. CONCLUSIONS AND RELEVANCE: In an older population, a Mediterranean diet
      supplemented with olive oil or nuts is associated with improved cognitive
      function. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN35739639.

PMID- 25961185
TI  - Goodbye, Sustainable Growth Rate-Hello, Merit-Based Incentive Payment System.

PMID- 25961187
TI  - Differential effects of overexpression of ERalpha and ERbeta in MCF10A
      immortalised, non-transformed human breast epithelial cells.
AB  - BACKGROUND: Cellular effects of oestrogen are mediated by two intracellular
      receptors ERalpha and ERbeta. However, to compare responses mediated through
      these two receptors, experimental models are needed where ERalpha and ERbeta are
      individually stably overexpressed in the same cell type. METHODS: We compared the
      effects of stable overexpression of ERalpha and ERbeta in the MCF10A cell line,
      which is an immortalised but non-transformed breast epithelial cell line without
      high endogenous ER expression. RESULTS: Clones of MCF10A cells were characterised
      which stably overexpressed ERalpha (10A-ERalpha2, 10A-ERalpha13) or which stably
      overexpressed ERbeta (10A-ERbeta12, 10A-ERbeta15). Overexpression of either
      ERalpha or ERbeta allowed induction of an oestrogen-regulated ERE-LUC reporter
      gene by oestradiol which was not found in the untransfected cells. Oestradiol
      also increased proliferation of 10A-ERalpha13 and 10A-ERbeta12 cells, but not
      untransfected cells, by 1.3-fold over 7 days. The phytoestrogen, genistein, which
      is reported to bind more strongly to ERbeta than to ERalpha, could induce
      luciferase gene expression from an ERE-LUC reporter gene at concentrations of 10
      6 M and 10-5 M but only in the clones overexpressing ERbeta and not in those
      overexpressing ERalpha. Clone 10A-ERbeta12 also yielded growth stimulation with
      10-6 M genistein. Finally, the overexpression of ERalpha, but not ERbeta, gave
      rise to increased growth in semi-solid methocel suspension culture in the
      presence of 70 nM oestradiol, suggesting that overexpression of ERalpha, but not
      ERbeta, produces characteristics of a transformed phenotype. CONCLUSIONS: This
      provides a model system to compare effects of oestradiol with other oestrogenic
      ligands in cells stably overexpressing individually ERalpha or ERbeta.

PMID- 25961186
TI  - High Maternal Serum Estradiol Levels Induce Dyslipidemia in Human Newborns via a
      Hepatic HMGCR Estrogen Response Element.
AB  - While the intrauterine environment is essential for the health of offspring, the
      impact of high maternal serum estradiol (E2) on lipid metabolism in offspring and
      the mechanisms are unknown. We found that ovarian stimulation (OS) could result
      in high E2 levels in women throughout pregnancy. Strikingly, their newborns
      showed elevated total cholesterol (TC) and low-density lipoprotein cholesterol
      (LDL-C) levels that were positively related with E2 in newborns. In vitro, E2
      dose-dependently stimulated TC and LDL-C secretion, and increased expression of
      the cholesterol synthesis rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA
      reductase (HMGCR) in HepG2 cells and mouse fetal hepatocytes. In vivo, high
      maternal E2 was detected and fetal livers also showed significantly higher HMGCR
      expression in an OS mouse model. Notably, an estrogen response element (ERE) was
      identified in the HMGCR promoter, indicating that high maternal serum E2 could up
      regulate HMGCR expression in fetal hepatocytes via an ERE that in turn induces
      elevated levels of TC and LDL-C in offspring. CONCLUSION: OS can induce a high
      maternal E2 environment, which up-regulates HMGCR expression in fetal hepatocytes
      via an ERE in the promoter, and induces elevated levels of TC and LDL-C in
      newborns that may be related to increased risk of metabolic disease in adulthood.

PMID- 25961188
TI  - Visualization of Stat3 and Stat5 transactivation activity with specific response
      element dependent reporter constructs integrated into lentiviral gene transfer
      vectors.
AB  - BACKGROUND: Signal transducer and activator of transcription 3 and 5 (Stat3 and
      Stat5) play important roles in cell differentiation, proliferation, apoptosis and
      inflammation. They are transiently activated by ligand-receptor interactions in
      normal cells but are often found to be constitutively active in cancer cells.
      Analysis of their activation pattern is therefore important for the description
      of developmental processes and the understanding of cellular transformation.
      MATERIALS AND METHODS: To visualize Stat3 and Stat5 transactivation activity in
      different cell types, we designed novel reporter constructs. These constructs
      comprise Stat3 or Stat5 specific promoter elements and reporter genes encoding
      beta-galactosidase or fluorescent proteins. These constructs were integrated into
      lentiviral gene transfer vectors facilitating efficient transduction of most cell
      types. RESULTS: The lentiviral reporter constructs were used to infect different
      cell types and their inducibility by activated Stat3 or Stat5 was measured. The
      Stat3-mCherry reporter was active in transduced tumor cells, which exhibit high
      levels of phosphorylated Stat3 and it was inducible in HepG2 liver cells by
      interleukin-6 treatment. The Stat5-LacZ reporter was active in cultured cells
      upon hormone induction of Stat5 and in primary mammary epithelial cells
      transplanted into cleared fat pads of mice during late pregnancy. CONCLUSION:
      These novel reporter constructs are valuable tools to investigate and to
      distinguish between Stat3 and Stat5 activity in primary cells and cancer cells.
      They will also be useful in the discovery of drugs targeting Stat3 or Stat5. They
      can also be employed to generate transgenic mice and track Stat activity during
      development.

PMID- 25961189
TI  - Effect of toremifene and ospemifene, compared to acolbifene, on estrogen
      sensitive parameters in rat and human uterine tissues.
AB  - BACKGROUND: Although the first generation selective estrogen receptor modulator
      (SERM) tamoxifen (TAM) is well known for its uterotrophic activity, this study
      compares the stimulatory effect of the TAM derivatives toremifene (TORE) and
      ospemifene (OSPE) on estrogen-sensitive parameters in rat and human uterine
      tissues. MATERIAL AND METHODS: Ovariectomized female rats were treated daily
      orally for 10 days with 0.75 mg/rat of TORE, OSPE or acolbifene (ACOL, a pure
      estrogen antagonist in the uterus and mammary gland), which was used for
      comparison. Human endometrial carcinoma Ishikawa cells were incubated for 5 days
      with increasing doses of compounds, in the absence or presence of 1 nM estradiol
      (E2). RESULTS: TORE and OSPE revealed 52% and 56% increases, respectively, in
      uterine weight, whereas ACOL had no effect. Similar effects were observed on
      vaginal weight. Endometrial epithelial height increased from 15.82+/-0.20 to
      48.94+/- 2.12 and 42.14+/-1.95 MUm with TORE and OSPE, respectively, whereas ACOL
      had no effect. Alkaline phosphatase activity, an estrogen-sensitive parameter in
      Ishikawa cells, was increased by 144% and 135% with OH-TORE and OH-OSPE,
      respectively. Owing to their intrinsic estrogenic activity, at maximal
      concentrations, OH-TORE and OH-OSPE blocked the stimulatory effect of E2 by only
      89% compared to 100% with ACOL. CONCLUSIONS: The present in vitro and in vivo
      data show similar stimulatory effects of 4-hydroxytoremifene (OH-TORE) and OH
      OSPE on estrogen-sensitive parameters. ACOL, a third generation SERM, has no
      effect on any of these parameters. Such data add to the potential uterine safety
      limitations of triphenylethylene-derived SERMs for long-term use in humans.

PMID- 25961190
TI  - Recent advances on the action of estrogens and progestogens in normal and
      pathological human endometrium.
AB  - Hormonal control in the development of the normal endometrium is of the utmost
      importance. It is well established that the two main hormones involved in this
      process are estradiol and progesterone, which are also implicated in the
      pathological conditions concerning endometriosis and endometrial carcinoma. There
      are two types of endometrial carcinoma: type I which represents 80%-90% is
      hormone-dependent, whereas the remainder is type II and is hormone-independent.
      The endometrial tissue contains all the enzymatic systems in the formation and
      transformation of the various hormones, including aromatases, sulfatases,
      sulfotransferases, hydroxysteroid dehydrogenases, hydroxylases, and
      glucuronidases. It is interesting to note that increased sulfatase activity is
      correlated with severity of endometriosis. An increased
      sulfatase/sulfotransferase ratio represents a poor prognosis in patients with
      endometrial carcinoma. Treatment with hormone replacement therapy
      (estrogens+progestogens), as well as with tibolone, is most effective in
      protecting this tissue by climacteric alterations, owing to the significant
      decrease of ovarian hormones. In conclusion, enzymatic control can open appealing
      perspectives to protect this organ from possible pathological alterations. 

PMID- 25961191
TI  - Testosterone and risk of breast cancer: appraisal of existing evidence.
AB  - The objective of this review was to examine data from preclinical, clinical and
      epidemiological studies to evaluate if testosterone (T) poses increased risk of
      breast cancer in women. Appraisal of the existing literature produced several
      lines of evidence arguing against increased breast cancer risk with T. These
      include: (i) Data from breast tumor cell lines treated with androgens did not
      corroborate the notion that T increases breast cancer risk. On the contrary,
      androgens appear to be protective, as they inhibit tumor cell growth. (ii) Many
      of the epidemiological studies claiming an association between T and breast
      cancer did not adjust for estrogen levels. Studies adjusted for estrogen levels
      reported no association between T and breast cancer. (iii) Data from clinical
      studies with exogenous androgen treatment of women with endocrine and sexual
      disorders did not show any increase in incidence of breast cancer. (iv) Women
      afflicted with polycystic ovary disease, who exhibit high levels of androgens do
      not show increased risk of breast cancer compared to the general population. (v)
      Female to male transsexuals, who receive supraphysiological doses of T for long
      time periods prior to surgical procedures, do not report increased risk of breast
      cancer. (vi) Finally, women with hormone responsive primary breast cancer are
      treated with aromatase inhibitors, which block conversion of androgens to
      estrogens, thus elevating androgen levels. These women do not experience
      increased incidence of contralateral breast cancer nor do they experience
      increased tumor growth. In conclusion, the evidence available strongly suggests
      that T does not increase breast cancer risk in women. 

PMID- 25961192
TI  - Preoperative low serum testosterone levels are associated with tumor
      aggressiveness in radical prostatectomy treated cancer patients.
AB  - BACKGROUND: The aim of this study was to characterize the aggressiveness of
      prostate cancer as assessed by the Gleason score (GS), the predominant Gleason
      pattern (pGP), and testosterone (T) serum concentration. METHODS: A total of 247
      patients, referred to our Department (from January 2007 to December 2009) for a
      radical prostatectomy, underwent preoperative T and bioavailable testosterone
      (samplings between 07:00 and 10:00 h). Serum determinations (radioimmunoassayed
      in a central laboratory). GS and pGP were determined in prostate biopsies and
      prostate tissue specimens. RESULTS: In biopsy specimens, a GS7 was observed in
      105 (43%) patients; 25 (10%) had pGP4. In prostate specimens, 163 (66%) had a
      GS7; 60 (24%) had pGP4. For prostate specimens, comparing the 75 patients with
      pGP4 (GS 4+3, 4+4 and 4+5) to the 172 with pGP3 (GS 3+3 and 3+4), T was lower
      (4.03 vs. 4.75 ng/mL, p=0.003) and prostrate-specific antigen (PSA) higher (11.1
      vs. 7.3 ng/mL, p<0.00001). Extra prostatic extension and positive margins were
      observed more frequently (52% vs. 18%, p<0.000001 and 29% vs. 15%, p=0.009,
      respectively). The 40 patients with T <3.0 ng/mL were larger (+5 kg, body mass
      index: +1.7 kg/m2), PSA was higher (9.9 vs. 8.2 ng/mL, p=0.07). They had a higher
      percent of GS with pGP4: 53% vs. 25% (p=0.0008). CONCLUSIONS: Aggressiveness of
      the tumor cannot be properly estimated by the GS and pGP found in biopsies. The
      pGP in prostate specimens is of paramount importance, particularly in the case of
      a Gleason 7, to appreciate the outcomes and to choose the treatment. Preoperative
      testosterone should be added to PSA determination to improve prediction of
      treatment outcomes.

PMID- 25961193
TI  - The androgen receptor drives the sex-specific expression of vascular cell
      adhesion molecule-1 in endothelial cells but not lipid metabolism genes in
      monocyte-derived macrophages.
AB  - BACKGROUND: Anecdotal evidence suggests that male sex hormones are
      proatherogenic. We hypothesized that the male sex hormone receptor, the androgen
      receptor (AR), acts as a molecular switch in sex-specific inflammatory signaling
      in vascular cells. MATERIALS AND METHODS: AR expression in human umbilical vein
      endothelial cells (HUVECs), human monocyte-derived macrophages (MDMs) or HeLa
      cells was modulated by transfection with AR siRNA or human AR cDNA expression
      vector. Activity and expression levels were measured by luciferase reporter
      assays, Western blotting or real-time PCR analysis. RESULTS: AR knockdown reduced
      expression of vascular cell adhesion molecule-1 (VCAM-1) in genetically male
      HUVECs. Conversely, AR upregulation in genetically female HUVECs induced VCAM-1
      expression and increased dihydrotestosterone-stimulated monocyte adhesion. Co
      transfection of an AR expression vector with VCAM-1 or NF-kappaB-reporter vectors
      into phenotypically female, AR-negative HeLa cells confirmed AR regulation of
      VCAM-1 expression as well as AR activation of NF-kappaB. AR upregulation was not
      sufficient to increase ICAM-1 levels in female HUVECs or lipoprotein metabolism
      gene expression in female MDMs, despite AR knockdown limiting expression in their
      male counterparts. CONCLUSIONS: AR acts as a molecular switch to induce VCAM-1
      expression. Low AR levels in female HUVECs limit NF-kappaB/VCAM-1 induction and
      monocyte adhesion and could contribute to the gender bias in cardiovascular
      disease. Unidentified factors in female cells limit induction of other
      proatherogenic genes not primarily regulated by NF-kappaB.

PMID- 25961194
TI  - Effects of LY117018 (a SERM analog of raloxifene) on tumor suppressor proteins
      and proliferation of breast cancer cells.
AB  - We have previously shown that presence of estradiol (E2) in the growth medium
      causes (i) proliferation of T47D breast cancer cells, (ii) elevation of p53
      levels, and (iii) hyperphos-phorylation of retinoblastoma protein (pRb). In the
      present study, we examined the expression of p53, phosphorylation state of pRb
      and proliferation of T47D cells in the presence of LY117018 (Courtesy of Lilly
      Research Laboratories), an analog of raloxifene, which is a known selective
      estrogen receptor modulator (SERM). The cells grown in charcoal-treated serum
      were treated with 1 nM E2 or different concentrations of LY117018 for 24 h. E2 or
      LY117018 treatments caused a 2- to 3-fold increase in the level of p53 and
      hyperphosphorylation of pRb. E2 treatment increased cell proliferation, whereas
      LY117018 treatment had no such effect but inhibited the E2-dependent cell
      proliferation. E2 and LY117018 treatments of T47D cells also caused differential
      effects on intracellular structures. Thus, LY117018 treatment induces changes in
      the level/activity of p53 and pRb and ultrastructure of T47D cells. Importantly,
      LY11708 inhibits estrogen-induced cell proliferation while mimicking E2 actions
      on p53 induction and pRb phosphorylation. The SERM also induced structural
      alterations in the T47D cells. 

PMID- 25961195
TI  - Quantitative determination and tissue distribution of human 11beta-hydroxysteroid
      dehydrogenase, hexose-6-phosphate dehydrogenase, glucose-6-phosphate transporter,
      glucocorticoid receptor and mineralocorticoid receptor mRNAs.
AB  - BACKGROUND: Glucocorticoid (GC) concentrations in peripheral tissues are
      precisely regulated by 11beta-hydroxysteroid dehydrogenase (HSD) isozymes. When
      considering the physiological effects of GC in various tissues, quantitative
      determination of these isozymes and other components involved in corticosteroid
      signaling is important and informative. We thus performed comprehensive
      determination of the expression of these mRNAs in a wide range of human tissues.
      METHODS: An absolute comparison of mRNA expression of human 11beta-HSD isozymes,
      hexose-6-phosphate dehydrogenase (H6PDH), glucose-6-phosphate transporter (G6PT),
      glucocorticoid receptors (GRs), and mineralocorticoid receptor (MR) was performed
      by real-time RT-PCR. RESULTS: Human 11beta-HSD type 1 mRNA was strongly expressed
      in the liver and placenta at comparatively high levels. H6PDH was expressed at
      low copy number, and comparatively high expression was observed in the kidney,
      testis, and ovary. G6PT expression was ubiquitous, but marked expression was
      observed in the liver, kidney, small intestine, and colon. GRalpha was also
      ubiquitously expressed at relatively high levels, which were approximately 10
      fold higher than those of MR, whereas GRbeta levels were below the detection
      limit in all tissues. 11beta-HSD type 2 was predominantly expressed in the
      kidney, small intestine and colon; however, copy numbers of these transcripts
      showed a nearly identical pattern to type 1. MR was observed in various tissues
      examined, but was not fully correlated to the distribution of 11beta-HSD type 2.
      CONCLUSIONS: The present quantitative results were partially consistent with
      previous studies. This quantification method can thus provide valuable
      information for understanding the physiological effects and physiological roles
      of glucocorticoid in humans.

PMID- 25961196
TI  - Congenital adrenal hyperplasia and the function of adrenal medulla.
AB  - OBJECTIVE: The most common form of congenital adrenal hyperplasia (CAH) is the
      deficiency of steroid 21-hydroxylase which results from deletion or mutation of
      the cytochrome P450 21-hydroxylase gene. The low level of glucocorticoids and in
      some cases low level of mineralocorticoids has an important pathophysiological
      influence on the axis of the hypothalamo-pituitary-adrenal cortex. DESIGN: Using
      determination of plasmatic metanephrine, normetanephrine and chromogranin A, we
      wanted to investigate the structure and function of adrenal medulla in patients
      with CAH, because adrenocortical and adrenomedullary systems are intimately
      linked anatomically and functionally. METHODS: Levels of plasmatic metanephrine,
      normetanephrine and chromogranin A were measured in our group of 37 patients (age
      range: 5-45 years, 18 females and 19 males) with the classic salt-wasting form of
      CAH. RESULTS: The reference range was 73% for metanephrine (<10 ng/L, 83.3%
      females, 63.2% males) and 59.5% for metanephrine (<15 ng/L, 72.2% females, 47.4%
      males). The concentration of plasmatic nephrines in the first quartile reference
      range was achieved in the case of metanephrine in all patients (<23 ng/L), and in
      the case of normetanephrine in 86.5% of patients (<42.5 ng/L). The level in
      chromogranin A was normal in all patients. No significant differences were found
      in plasmatic concentrations of nephrines and chromogranin A between males and
      females with CAH, nor was there a significant correlation with genetic results
      (severe or moderate salt-wasting form of CAH). CONCLUSION: Impaired secretion of
      glucocorticoids in patients with CAH leads to the structural changes in adrenal
      medulla which are expressed by low production of metanephrine, and to a lesser
      extent, normetanephrine.

PMID- 25961197
TI  - Effect of trenbolone acetate plus estradiol on transcriptional regulation of
      metabolism pathways in bovine liver.
AB  - BACKGROUND: The use of anabolic steroids is forbidden for food producing animals
      in the EU. Owing to the advantages of anabolics for production profitability,
      illegal application is appealing. Anabolics are known to influence gene
      expression of several tissues. We focused on the liver because of its important
      role in nutrient and hormone metabolism. The aim of the present study was to find
      differentially regulated metabolic pathways, which might be used as treatment
      biomarkers. MATERIAL AND METHODS: A total of 18 Nguni heifers were allocated
      equally to a control group and a treatment group and were implanted with Revalor
      H. Expression of 34 target genes was measured using reverse transcriptase
      quantitative polymerase chain reaction (RT-qPCR). RESULTS: Upregulation of
      androgen receptor and insulin-like growth factor 1 (IGF-1) and downregulation of
      IGF-2, insulin-like growth factor binding protein 2, steroid hormone binding
      globulin, insulin receptor alpha, insulin receptor beta, tyrosine
      aminotransferase, 17beta-hydroxy steroid dehydrogenase 2,3-hydroxy-methylglutaryl
      coenzym-A-synthase, cathepsin B, hepatocyte growth factor, steroidogenic acute
      regulatory protein, apolipoprotein 2 and tumor necrosis factor alpha was
      demonstrated. CONCLUSION: Several biochemical pathways showed different
      regulations on mRNA level under the influence of trenbolone acetate plus
      estradiol. The inhibition of nutrient metabolism and protein breakdown seems to
      support growth processes. IGF-1 plays an important role in growth and development
      and thus the upregulation of IGF-1 could be responsible for the stimulation of
      growth in treated animals. The upregulation of IGF-1 could also be revealed as a
      possible risk factor for the generation of artherosclerotic plaques, which are
      known as long-term side effects following the use of anabolic steroids. Principal
      components analysis of RT-qPCR results showed that both groups arrange together
      and can be clearly separated. Therefore, these might be used as possible
      biomarkers in bovine liver.

PMID- 25961198
TI  - Effect of long-term topical application of dehydroepiandrosterone (DHEA) and oral
      estrogens on morphology, cell proliferation, procollagen A1 and androgen receptor
      levels in rat skin.
AB  - BACKGROUND: After cessation of estrogen secretion by the ovaries at menopause,
      all estrogens and almost all androgens acting in the skin of postmenopausal women
      are synthesized locally from dehydroepiandrosterone (DHEA), a prohormone of
      adrenal origin that progressively declines with age. OBJECTIVE: To better
      understand the effects of DHEA on the skin, ovariectomized (OVX) rats were
      treated for 9 months with local topical application of DHEA compared with oral
      conjugated equine estrogens. MATERIALS AND METHODS: Morphological evaluation,
      immunohistochemistry for androgen receptor (AR) and Cdc47 proliferation marker,
      and in situ hybridization for procollagen A1 were performed on dorsal skin.
      RESULTS: Local topical DHEA application increased the thickness of the granular
      cell layer and total epidermis in OVX animals, whereas systemic estrogens had no
      significant effect. Although DHEA did not affect total dermal thickness, a 190%
      increase in dermal procollagen A1 mRNA was observed. Moreover, DHEA treatment
      decreased hypodermal thickness by 47% and increased skin muscle thickness by 58%.
      In the epidermis, DHEA induced a non-significant increase in cell proliferation,
      whereas AR labeling was increased in both the epidermis and dermis by DHEA.
      CONCLUSIONS: Although estrogens did not significantly modify any of the above
      mentioned parameters, the androgenic action of DHEA induced significant changes
      in all skin layers, without any sign of toxicity or lack of tolerance to DHEA
      after a 9-month local application of 4% (80 mg/kg) DHEA on the skin.

PMID- 25961199
TI  - Mechanisms of angiotensin II-induced ERK1/2 activation in fetal cardiomyocytes.
AB  - Fetal cardiomyocytes have been utilized in studies on myocardial repair in the
      damaged hearts of rodents and other species. Changes in angiotensin II (Ang II)
      receptor expression, especially decline of its type II receptor (AT2), are known
      to occur during the growth of cardiomyocytes from fetus to adult. However, the
      extent to which changes in the signaling pathways of Ang II type I (AT1) and AT2
      receptors via p42/44 mitogen-activated protein kinase (ERK1/2) activation affect
      the physiological and pathophysiological functions in cardiomyocytes has not been
      defined. The roles of these receptors were analyzed by confocal fluorescence
      microscopy, immunoblot analysis, reverse transcription PCR, measurement of
      intracellular 3',5'-cyclic AMP levels and siRNA technology in cultured rat fetal
      cardiomyocytes. These studies revealed that Gq is required for Ang II-induced
      ERK1/2 activation via the synergy of AT1 and AT2 receptors. It has also been
      shown that phospholipase Cbeta1, protein kinase Calpha and protein kinase A
      mediate the feedback inhibition of ERK1/2 activation via c-Raf and/or other
      intermediate signaling molecules. The observed mechanism of Ang II-induced ERK1/2
      activation in fetal cardiomyocytes could be relevant to the understanding of
      cardiomyocyte development and turnover, as well as clinical approaches using
      protein- and cell-based therapy for diseases such as heart failure. 

PMID- 25961200
TI  - Administration of testosterone to elderly hypogonadal men with Crohn's disease
      improves their Crohn's Disease Activity Index: a pilot study.
AB  - BACKGROUND: Both elevated and depressed testosterone (T) levels have been
      reported in Crohn's disease (CD). In this pilot study, effects of T
      administration on CD were assessed. MATERIALS AND METHODS: A total of 13 men with
      CD, aged 45-67 years, had subnormal plasma T (mean+/-SD=9.0+/-1.4 nmol/L)
      (reference >12.0); they were compared to a group of 110 men of similar age with
      sexual and urological problems whose plasma T was also subnormal: 10.4+/-1.4
      nmol/L (p=0.02). All received treatment with parenteral T undecanoate for 24
      months. The Crohn's Disease Activity Index (CDAI) was assessed as an indicator of
      the severity of the disease every 3 months. Levels of T and C-reactive protein
      (CRP) were compared between the 13 men with CD and the other men in this study.
      Values of CDAI and CRP were followed-up. RESULTS: CRP levels were 22.7 mg/dL (95%
      confidence interval of the mean: 14.9-34.3) in the 13 men with CD vs. 3.5 (2.9
      4.1) in 107 control men (p=0.001). Upon normalization of serum T, there was a
      significant decline of CDAI (from 243+/-19 to 89+/-9), CRP levels from 22.7+/-8.1
      to 6.9+/-2.9 mg/dL, and white blood cell count. Hemoglobin/hematocrit increased
      significantly. CONCLUSIONS: Upon normalization of plasma T the CDAI and CRP
      levels decreased in hypogonadal patients with CD. The mechanism of this
      improvement could be through immunosuppressive effects of T, reducing chronic
      inflammation of the intestinal wall in CD.

PMID- 25961201
TI  - Human type 3 5alpha-reductase is expressed in peripheral tissues at higher levels
      than types 1 and 2 and its activity is potently inhibited by finasteride and
      dutasteride.
AB  - 5alpha-Reductases are crucial enzymes involved in the biosynthesis of
      dihydrotestosterone, the most potent natural androgen. To date, three types of
      5alpha-reductases, chronologically named types 1, 2 and 3 5alpha-reductases
      (SRD5a-1, 2 and 3) have been described. In the present paper, we characterized
      the activity and compared the mRNA expression levels of SRD5a-3 with those of
      SRD5a-1 and 2 in various human tissues, and determined its sensitivity to
      finasteride and dutasteride. We have established HEK-293 cell line that stably
      expressed SRD5a-3 for studying its activity and the inhibitory effect of
      finasteride, using [14C]labeled steroids. mRNA expression levels were quantified
      using real-time PCR in many male and female human tissues including the prostate,
      adipose tissue, mammary gland, as well as breast and prostate cancer cell lines.
      Incubation of HEK-SRD5a-3 cells with [14C]4-androstenedione and [14C]testosterone
      allowed us to show that SRD5a-3 can catalyze very efficiently both substrates 4
      androstenedione and testosterone into 5alpha-androstanedione and
      dihydrotestosterone, respectively. We observed that the affinity of the enzyme
      for 4-androstenedione is higher than for testosterone. The activity of SRD5a-3
      and SRD5a-2 are similarly sensitive to finasteride, whereas dutasteride is a much
      more potent inhibitor of SRD5a-3 than SRD5a-2. Tissue distribution analysis shows
      that SRD5a-3 mRNA expression levels are higher than those of SRD5a-1 and SRD5a-2
      in 20 analyzed tissues. In particular, it is highly expressed in the skin, brain,
      mammary gland and breast cancer cell lines, thus suggesting that SRD5a-3 could
      play an important role in the production of androgens in these and other
      peripheral tissues. 

PMID- 25961202
TI  - Comparison of oral versus transdermal testosterone supplementation in hypogonadal
      men.
AB  - OBJECTIVE: To compare mean serum total testosterone, bioavailable-testosterone,
      and dihydrotestosterone levels between transdermal testosterone and oral
      testosterone undecanoate treatment. METHODS: Multicentre, randomized, cross-over
      study; 44 men >18 years, testosterone <=2.5 ng/mL. Two patches (Testopatch(r))
      every other day in the morning or two capsules Pantestone(r) 40 mg bid in each 22
      day period. Hormone serum levels of four blood samples over the first and last 48
      h of each treatment period. RESULTS: Mean age 49 years. Mean testosterone before
      inclusion 1.99 ng/mL. Mean testosterone serum levels over the last 48 h of
      Testopatch treatment were superior to Pantestone (4.64 vs. 2.58 ng/mL, p<0.001).
      Testosterone trough levels at the end of each treatment period were significantly
      higher for Testopatch (3.15 vs. 2.45 ng/mL, p<0.01). Bioavailable-testosterone
      levels over the first and last 48 h of treatment were significantly greater with
      Testopatch than with Pantestone (p=0.001 and p<0.01). Dihydrotestosterone levels
      over the first and last 48 h of treatment (0.71 vs. 1.05 ng/mL and 0.68 vs. 0.89
      ng/mL) as well as at trough (0.59 vs. 0.96 ng/mL) were significantly lower with
      Testopatch than with Pantestone (p<0.001, p<0.05, and p<0.001). SHBG levels
      decreased by Pantestone but not by Testopatch (p<0.001). CONCLUSIONS: Testopatch
      was superior to Pantestone to increase testosterone and bioavailable-testosterone
      levels in hypogonadal men from the first days and throughout the three weeks of
      treatment. Pantestone increased dihydrotestosterone to a larger extent and
      decreased SHBG.

PMID- 25961203
TI  - Target deletion of the bifunctional type 12 17beta-hydroxysteroid dehydrogenase
      in mice results in reduction of androgen and estrogen levels in heterozygotes and
      embryonic lethality in homozygotes.
AB  - 17beta-Hydroxysteroid dehydrogenases (17beta-HSDs) are enzymes issued from
      convergent evolution of activity from various ancestral genes having different
      functions. Type 12 17beta-HSD (17beta-HSD12) was described as a bifunctional
      enzyme, involved in the biosynthesis of estradiol (E2) and the elongation of very
      long chain fatty acid (VLCFA). It catalyzes selectively the transformation of
      estrone (E1) into estradiol (E2) in human and primates, whereas in the mouse and
      Caenorhabditis elegans the enzyme catalyzes the 17beta-reduction of both
      androgens and estrogens. It is also able to catalyze the reduction of 3-keto
      acylCoA into 3-hydroxy-acylCoA in the elongation cycle of VLCFA biosynthesis. To
      further understand the physiological role of 17beta-HSD12, we performed targeted
      disruption of the Hsd17b12 gene by substituting exons 8 and 9 that contain the
      active site with a neomycin cassette. The data indicate that heterozygous
      (HSD17B12+/-) mice are viable with reduced levels of sex steroids, whereas
      homozygous (HSD17B12-/-) mice show embryonic lethality. The present data are in
      agreement with the bifunctional activities of 17beta-HSD12 suggesting that the
      VLCFA elongation activity, having its origin in the yeast, is most probably
      responsible for embryonic lethality in HSD17B12-/-, whereas the more recently
      acquired 17beta-HSD12 activity is responsible for reduced sex steroid levels in
      HSD17B12+/-. 

PMID- 25961204
TI  - Generating diversity in glucocorticoid receptor signaling: mechanisms, receptor
      isoforms, and post-translational modifications.
AB  - Glucocorticoids are necessary for life after birth and regulate numerous
      homeostatic functions in man, including glucose homeostasis, protein catabolism,
      skeletal growth, respiratory function, inflammation, development, behavior, and
      apoptosis. In a clinical setting, they are widely used as anti-inflammatory
      agents to control both acute and chronic inflammation. Unfortunately, owing to
      their broad range of physiological actions, patients treated with glucocorticoids
      for long periods of time experience a variety of serious side effects, including
      metabolic syndrome, bone loss, and psychiatric disorders including depression,
      mania, and psychosis. Our understanding of how one hormone or drug regulates all
      of these diverse processes is limited. Recent studies have shown that multiple
      glucocorticoid receptor isoforms are produced from one gene via combinations of
      alternative mRNA splicing and alternative translation initiation. These isoforms
      possess unique tissue distribution patterns and transcriptional regulatory
      profiles. Owing to variation in the N-terminal and C-terminal length of
      glucocorticoid receptor isoforms, different post-translational modifications
      including ubiquitination, phosphorylation, and sumoylation are predicted,
      contributing to the complexity of glucocorticoid signaling. Furthermore,
      increasing evidence suggests that unique glucocorticoid receptor isoform
      compositions within cells could determine the cell-specific response to
      glucocorticoids. In this review, we will outline the recent advances made in the
      characterization of the transcriptional activity and the selective regulation of
      apoptosis by the various glucocorticoid receptor isoforms. 

PMID- 25961205
TI  - Risk of breast cancer during hormone replacement therapy: mechanisms.
AB  - Regarding estrogen replacement therapy, two main mechanisms have to be considered
      for it to be discussed as a potential carcinogen in the breast, and also
      considering the World Health Organization definition of estrogens and
      estrogen/progestogen combinations as "carcinogenic": (i) the
      proliferative/apoptotic effects on already pre-existing estrogen-sensitive cancer
      cells and (ii) the production of possible genotoxic estrogen metabolites. By
      addition of the progestogen component, as is usual in non-hysterectomized women,
      both mechanisms can lead to an increased risk compared to estrogenonly therapy.
      The detailed mechanisms underlying the development of the benign breast
      epithelial cell into clinically relevant breast cancer cells are very
      complicated. Based on these mechanisms, the following simplified summary of the
      main steps explains that: (i) an increased risk cannot be excluded, (ii)
      especially when estrogens are combined with progestogens, but (iii) there are
      differences between the preparations used in therapy; (iv) the risk seems to be
      very rare, needing very special cellular and extracellular conditions, (v) and
      could even be decreased in special situations of estrogen therapy. It is
      concluded that when critically reviewed, an increased risk of breast cancer
      during hormone replacement therapy cannot be excluded in very rare cases.
      Definitive mechanistic evidence for a possible causal relationship with
      carcinogenesis still remains open. 

PMID- 25961206
TI  - Circulating steroid hormones in prostate carcinogenesis. Part 1 - Androgens.
AB  - The aim of this review is to identify circulating steroids associated with
      prostate cancer (PCa) in bibliographic reports. First, we summarize chronological
      reports comparing circulating steroid levels in men with a high risk of PCa, such
      as African-Americans (AAs), with men having a lower risk. Higher testosterone
      plasma levels in young AA men have been reported. However, the difference between
      AAs and Caucasians decreases with age. When measured, dihydrotestosterone (DHT)
      was found to be higher in AAs; however, these results must be taken with caution,
      as immunological assay of this steroid is difficult. Second, we summarize
      chronological reports concerning circulating steroids assayed in blood samples
      drawn several years before a diagnosis of PCa was made, compared to controls.
      These nested case-control studies did not lead to straightforward conclusions
      regarding an increase in circulating testosterone. However, large collaborative
      studies showed a trend of a decrease in plasma sex hormone binding globulin,
      consequently an increase in bioavailable plasma testosterone in PCa. These nested
      case-control studies failed to associate plasma DHT levels with PCa risk. Third,
      we summarize numerous chronological publications relating plasma concentrations,
      measured at the time of PCa diagnosis. Numerous results showed a decrease in
      plasma testosterone levels in aggressive PCa (high Gleason score, advanced stage
      with positive surgical margins). Testosterone levels returned to normal several
      months after prostatectomy. All plasma hormone assay levels were always carried
      out using immunological methods. We recommend replacing this methodology by mass
      spectrometry coupled with gas chromatography or liquid chromatography in these
      epidemiologic studies. 

PMID- 25961207
TI  - Upregulation of AIB1, aromatase and ERalpha provides long-term estrogen-deprived
      human breast cancer cells with a mechanistic growth advantage for survival.
AB  - To investigate the mechanisms by which breast cancer cells adapt and are able to
      grow during estrogen deprivation, human estrogen receptor-alpha (ERalpha)
      positive breast cancer cells stably transfected with the aromatase gene (MCF-7Ca)
      were cultured in steroid-depleted medium for 6-8 months until they started
      proliferating. Compared with the parental MCF-7Ca cells, long-term estrogen
      deprived UMB-1Ca cells exhibited increased aromatase activity (2000%), AIB1
      expression (3500%) and ERalpha expression (100%). When MCF-7Ca cells were
      isolated from tumors of mice treated for 12 months with an aromatase inhibitor,
      letrozole, ERalpha was reduced (50%) whereas AIB1 levels were increased (>1000%),
      suggesting that the mechanism of estrogen deprivation might predetermine the
      signaling pathway utilized. To a lesser extent long-term estrogen-deprived MCF-7
      cells (LTED) displayed an increase in AIB1, ERalpha and aromatase activity.
      Consistent with other findings, the growth of the LTED cells was inhibited by
      estradiol and antiestrogens, whereas the UMB-1Ca cells were slightly stimulated
      by estradiol and inhibited by antiestrogens and letrozole. In LTED cells treated
      with estradiol, levels of AIB1 and ERalpha (95%) were reduced. Interestingly,
      estradiol treatment caused no change in AIB1 and ERalpha expression in the UMB
      1Ca cells which might explain the differential growth effect of the cells to
      estradiol. Together, these results demonstrate that estrogen deprivation results
      in the upregulation of the estrogen signaling pathway at the level of AIB1,
      ERalpha and aromatase, which might attenuate ER-mediated transcription
      representing one mechanism by which tumors adapt to proliferation in a low
      estrogenic environment. 

PMID- 25961208
TI  - Lack of substrate inhibition in a monomeric form of human cytosolic SULT2A1.
AB  - Mammalian cytosolic sulfotransferases (SULTs) frequently show substrate
      inhibition during the sulfation of increasing concentrations of substrates.
      SULT2A1, a major human liver isoform responsible for the conjugation of
      hydroxysteroids, bile acids and aliphatic hydroxyl groups in drugs and
      xenobiotics, is a homodimer and displays substrate inhibition during the
      conjugation of dehydroepiandrosterone (DHEA). Maltose binding protein (MBP)
      SULT2A1 fusion protein, produced as an intermediate step in the purification of
      the SULT2A1 homodimer, elutes during size exclusion chromatography as a monomer.
      The initial-rate parameters (Km and Vmax) of the monomer (MBP-SULT2A1) and native
      SULT2A1 dimer for DHEA sulfation are extremely similar; however, the monomer is
      not inhibited by DHEA. Intrinsic fluorescence studies show that two DHEA
      molecules bind each SULT2A1 subunit, one in the catalytic site and one in an
      apparent allosteric site. Lack of dimerization in the MBP-SULT2A1 fusion protein
      decreased the Kd for binding of DHEA at the allosteric site. These results
      suggest that formation of the homodimer is associated with structural re
      arrangements leading to increased DHEA binding at an allo-steric site that is
      associated with substrate inhibition. 

PMID- 25961209
TI  - A validated and rapid high-performance liquid chromatography method for the
      quantification of conversion of radio-labelled sex steroids.
AB  - The 17beta-hydroxysteroid dehydrogenase enzymes modify the availability of potent
      sex steroids and have thus attracted interest in the study of several steroid
      dependent pathologies including breast, endometrial and prostate cancers. An
      increased awareness of the importance of steroidogenic enzymes has brought forth
      a demand for efficient assays to study the effects of individual enzymes on
      steroid levels. Methods used for assessing steroid conversion are often laborious
      and frequently involve hazardous sample preparation steps. We developed and
      validated an optimised simple method for sample preparation of sex steroids using
      protein precipitation by the addition of zinc sulphate/sodium hydroxide. The
      interconversion of radio-labelled oestrogens and androgens was quantified using
      high-performance liquid chromatography separation of oestrone, oestradiol,
      androstenedione and testosterone followed by online radiometric flow
      scintillation analysis. The method, which can be applied for assessing, e.g., the
      efficacy of inhibitors of steroidogenic enzymes, was successfully used for
      evaluating oestrogenic interconversion in breast cancer cell lines MCF7 and T
      47D. 

PMID- 25961210
TI  - Sex steroids and breast cancer metastasis.
AB  - Sex steroids, particularly estrogen and progesterone, promote normal breast
      tissue growth and differentiation. Prolonged exposure of estrogen and/or
      progesterone is considered a risk factor for breast cancer carcinogenesis, and
      the effects of sex steroids on breast cancer metastasis are controversial.
      Emerging evidence indicates that sex steroids regulate breast cancer metastatic
      processes via nongenomic and genomic mechanisms. Through the regulation of actin
      binding proteins estrogen and progesterone rapidly provoke actin cytoskeleton
      reorganization in breast cancer cells, leading to formation of membrane
      structures facilitating breast cancer cell migration and invasion. In addition,
      steroid receptors interact and trans-activate receptor tyrosine kinases
      (including epidermal growth factor receptor and insulin-like growth factor
      receptor), resulting in growth factor-like effects that promote cancer cell
      invasive behavior. Moreover, sex steroids regulate the expression of metastasis
      associated molecules, such as E-cadherin, matrix metalloproteinases, growth
      factors, chemokines and their receptors, leading to epithelial-to-mesenchymal
      like transition. However, there is also evidence that sex steroids and their
      receptors protect against breast cancer cell invasiveness through distinct
      mechanisms. Here, we present an overview of the currently identified actions of
      sex steroids on breast cancer metastasis and their potential clinical
      implications. 

PMID- 25961211
TI  - Cancer protection of soy resembles cancer protection during pregnancy.
AB  - It has been established that carrying a pregnancy to full-term at an early age
      can protect against contracting cancer by up to 50% in later life. The
      trophoblast theory of cancer states that trophoblast and cancer tissue are very
      similar. New findings suggest that the loss of fetal cells during pregnancy
      resemble those cells responsible for causing metastasis in cancer. Fetal cells
      and spreading cancer cells are highly proliferative. They are similar to stem
      cells, exhibiting no or low hormone receptor expression, and require a hormone
      receptor independent mechanism for control. Control of membrane stability during
      pregnancy is of vital importance for a successful pregnancy and is mediated by
      androstenediol and 2-methoxyestradiol. 2-Methoxyestradiol has no hormone receptor
      affinity and elicits strong anticancer effects particularly against cancer stem
      cells and fetal cells, for which currently no treatment has yet been established.
      There is a discussion whether pregnancy reduces cancer stem cells in the breast.
      Soy isoflavones are structurally similar to both hormones, and elicit strong
      anticancer effects and antiangiogenesis via inhibition of NF-kappaB, even in
      hormone receptor independent breast cancers seen in epidemiologic studies. The
      trophoblast theory of cancer could help to explain why soy baby nutrition
      formulas have no effect on baby physiology, other than the nutritional aspect,
      although soy elicits many effects on the adult immune system. To survive the
      immune system of the mother, the immune system of the fetus has to be separated;
      otherwise, the reduction of the immune system in the mother, a necessary feature
      for the blastocyst to grow, would immediately reduce the immunity for the fetus
      and endanger its survival. Similar to a fetus, newly born babies show immune
      insensitive to Th1 and Th2 cytokines, which are necessary and crucial for
      regulating the immune system of the mother, thus raising the risk of the baby of
      developing allergies and neurodermatitis. Gene expression studies in vitro as
      well as in circulating tumor cells from patients consuming a fermented soy
      product support the antiangiogenic as well as antiproliferative effects of soy. 

PMID- 25961212
TI  - Expression of 5alpha-reductase type 1 in breast cancer and adjacent non-malignant
      tissue: an immunohistochemical study.
AB  - Intratumoral biosynthesis of sex steroids is thought to play a role in the
      pathogenesis and development of human breast cancer. There is evidence that
      androgens can inhibit the development and progression of breast cancer. Among the
      enzymes involved in the biosynthesis of androgens, 5alpha-reductase plays a key
      role by reducing testosterone to dihydrotestosterone, the most potent androgen.
      Two isoforms of 5alpha-reductase have been characterized and 5alpha-reductase
      type 1 is predominant in breast cancer tissue. We developed specific antibodies
      to 5alpha-reductase type 1 and studied the expression of the enzyme in 84
      specimens of breast carcinoma and adjacent non-malignant tissues by
      immunohistochemistry. The results were correlated with the expression of androgen
      receptor, estrogen receptor alpha, progesterone receptor and CDC47, a cell
      division marker as well as the tumor stage, tumor size, nodal status and
      menopausal status. The expression of 5alpha-reductase type 1 in 61% of breast
      cancer specimens appeared significantly lower than that observed in normal
      adjacent tissues (87% of cases being positive). There was no significant
      correlation between 5alpha-reductase type 1 expression and the
      clinicopathological parameters studied. The decrease in 5alpha-reductase type 1
      expression in breast cancer as compared to that observed in the adjacent normal
      tissues could play a role in the development and/or progression of the cancer by
      modifying the intratumoral levels of androgens. 

PMID- 25961213
TI  - Nomegestrol acetate is an anti-aromatase agent in human MCF-7aro breast cancer
      cells.
AB  - BACKGROUND: The progestogen nomegestrol acetate (NOMAC), a 17alpha-hydroxy-nor
      progesterone derivative (LUTENYL(r)) is largely used as an oral contraceptive and
      to treat menopausal complaints. In previous studies, we demonstrated that NOMAC
      is an anti-sulfatase agent in MCF-7 and T-47D breast cancer cells. In this study,
      we explore the effect of NOMAC on aromatase activity in a stable aromatase
      expressing human breast cancer cell line: MCF-7aro. MATERIALS AND METHODS: Cells
      were incubated with physiological concentrations of androgen substrates [3H]
      testosterone or [3H]-androstenedione (5*10-9 mol/L) alone, or in the presence of
      NOMAC (5*10-5 mol/L-5*10-8 mol/L) for 24 h at 37 degrees C. [3H]-Estradiol (E2),
      [3H]-estrone (E1), [3H]-testosterone and [3H]-androstenedione were characterized
      by thin layer chromatography and quantified using the corresponding standard.
      RESULTS: Aromatase activity levels are high in MCF-7aro cells because the [3H]-E2
      concentration after incubation of [3H]-testosterone was 5.8+/-0.31 pmol/mg DNA in
      non-treated cells. At concentrations of 5*10-5 mol/L, 5*10-6 mol/L and 5*10-7
      mol/L NOMAC significantly inhibits this conversion by 49.7%, 29.9% and 18.1%,
      respectively. After [3H]-androstenedione incubation, similar inhibition levels
      were observed with NOMAC for [3H]-E1 formation; whereas, inhibition of [3H]-E2
      production, which implicates 17beta-hydroxysteroid dehydrogenase activity in this
      pathway, is greater because NOMAC also inhibits this enzyme. CONCLUSION: The MCF
      7aro cell line shows high aromatase activity and NOMAC can act as an anti
      aromatase agent by inhibiting this activity. This is an important new effect of
      this progestogen. Because NOMAC can also inhibit sulfatase activity in breast
      cancer cells, we suggest that this dual effect of NOMAC has attractive
      possibilities for clinical trials.

PMID- 25961214
TI  - Editorial.

PMID- 25961215
TI  - Biological responses of progestogen metabolites in normal and cancerous human
      breast.
AB  - At present, more than 200 progestogen molecules are available, but their
      biological response is a function of various factors: affinity to progesterone or
      other receptors, their structure, the target tissues considered, biological
      response, experimental conditions, dose, method of administration and metabolic
      transformations. Metabolic transformation is of huge importance because in
      various biological processes the metabolic product(s) not only control the
      activity of the maternal hormone but also have an important activity of its own.
      In this regard, it was observed that the 20-dihydro derivative of the progestogen
      dydrogesterone (Duphaston(r)) is significantly more active than the parent
      compound in inhibiting sulfatase and 17beta-hydroxysteroid dehydrogenase in human
      breast cancer cells. Estrone sulfatase activity is also inhibited by
      norelgestromin, a norgestimate metabolite. Interesting information was obtained
      with a similar progestogen, tibolone, which is rapidly metabolized into the
      active 3alpha/3beta-hydroxy and 4-ene metabolites. All these metabolites can
      inhibit sulfatase and 17beta-hydroxysteroid dehydrogenase and stimulate
      sulfotransferase in human breast cancer cells. Another attractive aspect is the
      metabolic transformation of progesterone itself in human breast tissues. In the
      normal breast progesterone is mainly converted to 4-ene derivatives, whereas in
      the tumor tissue it is converted mostly to 5alpha-pregnane derivatives. 20alpha
      Dihydroprogesterone is found mainly in normal breast tissue and possesses
      antiproliferative properties as well as the ability to act as an anti-aromatase
      agent. Consequently, this progesterone metabolite could be involved in the
      control of estradiol production in the normal breast and therefore implicated in
      one of the multifactorial mechanisms of the breast carcinogenesis process. In
      conclusion, a better understanding of both natural and synthetic hormone
      metabolic transformations and their control could potentially provide attractive
      new therapies for the treatment of hormone-dependent pathologies. 

PMID- 25961216
TI  - Mechanisms for differential effects between natural progesterone and synthetic
      progestogens on normal breast tissue.
AB  - Both epidemiological studies and experimental data on normal breast tissue
      suggest increased cancer risk, proliferation and mammographic breast density (MD)
      during hormone therapy (HT) containing synthetic progestogens in traditional
      doses, and the relative risk or RR is approximately 1.5-3 (for women treated vs.
      untreated with the above therapies), proliferation levels of normal breast
      epithelial cells of around 10% and increase in MD in up to around 50% of women
      during treatment. Dose-response relationships have been inferred by correlations
      between progestogens as levonorgestrel, norethisterone acetate and
      medroxyprogesterone acetate on the one hand and proliferation and/or MD on the
      other hand, and of indications of lower relative risk of breast cancer with
      modern low or ultra-low dose HT. In contrast, natural progesterone endogenously
      during the menstrual cycle has a weak effect and exogenous estrogen in
      combination with oral micronized progesterone in HT has shown to yield an
      indifferent effect on proliferation. Furthermore, in epidemiological studies such
      as the French E3N cohort, these combinations have not shown any risk increase for
      breast cancer for at least 5 years of treatment. Experimental data supporting or
      not supporting the view that the main proliferative mechanism for natural
      progesterone is through binding to its nascent progesterone receptors is
      discussed as well as the pros and cons that the non-physiological higher
      proliferation levels induced by synthetic progestogens is mainly mediated through
      interaction with potent growth factors and their paracrine and/or cell signaling
      pathways. 

PMID- 25961217
TI  - Antigonadotropic progestogens as contraceptive agents in women with
      contraindication to combined pill.
AB  - Synthetic progestogens belong to different pharmacological classes and are mixed
      steroids. They display different properties due to their various affinities to
      the different steroid receptors. In addition, the dosage used can modify their
      side effects. Normethyltestosterone used at minimal doses, also called
      progestogen only pill (POP), constitute the standard recommended hormonal
      contraception for women with vascular and metabolic contraindications to combined
      pill (COC). However, POP efficacy and gynecological tolerance are limited. We
      have developed for more than 20 years in France the use of two pregnane
      derivatives as contraceptive agents in women with contraindication to COC.
      Chlormadinone acetate and cyproterone acetate have different antigonadotropic
      potencies but remain neutral on vascular risk. We have analyzed the efficacy,
      vascular and gynecological tolerances in 187 women with systemic lupus
      erythematous with or without antiphospholipids. Venous thrombosis and arterial
      events rates were lower than those reported in the literature. The current
      experience in women with thrombophilia is similar as reported in a series of 150
      patients. In addition, we have also used antigonadotropic progestins in women
      with hereditary angioedema (HAE) types I, II or III. HAE symptoms can be induced
      or worsened by COC. We could demonstrate a significant improvement of the
      symptoms in most women with HAE under antigonadotropic progestins. Gynecological
      and general tolerances were satisfactory. In conclusion, antigonadotropic
      progestins could have clinical positive benefits as contraceptive agents in women
      with contraindication to COC. 

PMID- 25961218
TI  - Progestogen effects at vascular level: the endothelial cells.
AB  - Progesterone and progestogens are active molecules on the cardiovascular system.
      However, their action is not as well-characterized as the effects of estrogens.
      Data of the last clinical trials suggest the possibility of harmful
      cardiovascular effects of progestogens, and the debate on the role of
      progesterone and progestins on the vascular wall is open. From an experimental
      point of view, each progestogen presents typical effects on the cardiovascular
      system and their administration results in diverse modifications of the effects
      of estrogens, sometimes acting synergically, others being neutral or antagonizing
      effects of estrogens. In this paper, we review the most important data from in
      vivo and in vitro studies which have been published on the effects of
      progesterone and progestogens on vascular cells. Endothelium is a target tissue
      for sex steroids and progesterone is able to regulate endothelial cell function
      and morphology. Even if the perfect molecule does not exist, the understanding of
      the molecular basis of each progestogen in vascular tissue is therefore of
      paramount importance for the most appropriate use with an optimal cardiovascular
      profile. 

PMID- 25961219
TI  - Progestogens for treatment and prevention of pregnancy disorders.
AB  - Progesterone appears to be the dominant hormone not only establishing a proper
      secretory endometrial development but also adequate decidualization to establish
      pregnancy and sustain pregnancy development. Progesterone is the natural
      immunoregulator to control the maternal immune system and not to reject the
      allogeneic fetus. There are two sources of progesterone: corpus luteum first and
      placenta later. Three progestogens can be used in pregnancy: (i) progesterone
      (per os, intravaginal and intramuscular), (ii) dydrogesterone (per os), and (iii)
      17alpha-hydroxyprogesterone caproate (intramuscular). There are three
      indications, for which these progestogens can be clinically used either for
      treatment or prevention: (i) first trimester threatened and recurrent (habitual)
      abortion, (ii) premature labor/premature birth, and (iii) pre-eclampsia
      (hypertension in pregnancy). The available data are limited and only partially
      randomized. In threatened abortion the use of progesterone, dydrogesterone and
      17alpha-hydroxyprogesterone caproate leads to a significant improved outcome,
      when at the time of threatened abortion a viable fetus has been ascertained by
      ultrasound. For prevention of recurrent abortion there are also some data
      indicating a significant effect compared with women without progestogen
      treatment. Prevention of preterm birth by progestogens (progesterone vaginally,
      orally and 17alpha-hydroxyprogesterone caproate intramuscularly) was
      significantly effective. The main study groups include pregnant women with a
      previous history of premature birth. However, also in women with shortened cervix
      use of progesterone seems to be helpful. The studies done so far in women with
      risk factors for pre-eclampsia or established pre-eclampsia were based on
      parenteral progesterone application. However, new studies are urgently needed. 

PMID- 25961220
TI  - Dysfunctional uterine bleeding: from adolescence to menopause.
AB  - Dysfunctional uterine bleeding (DUB) is defined as excessive or prolonged uterine
      bleeding in premenopausal women that is not caused by pelvic pathology,
      medications, systemic disease or pregnancy. It is a common condition that can
      lead not only to physical symptoms such as iron deficiency, anaemia, cramps and
      fatigue, but also has significant psychological and social effects that impair a
      woman's quality of life. Progesterone is highly important in the regulation of
      menstrual bleeding and a progesterone-deficient anovulatory state is a common
      cause of DUB. There are a wide range of treatment options available including
      hormonal therapies (oral cyclical progestogens, depot progestogens, progestogen
      releasing intrauterine devices, combined oral contraceptives, danazol,
      gonadotrophin-releasing hormone analogues and hormone replacement therapy), non
      hormonal therapies (non-steroidal anti-inflammatory drugs and antifibrinolytic
      drugs) and surgery (hysterectomy and endometrial ablation). The choice of
      appropriate therapy should be based on factors such as the mechanism behind the
      DUB, which symptoms are most problematic, and the woman's need for fertility or
      contraception. However, there is currently a lack of clinical evidence to help
      support these decisions. 

PMID- 25961221
TI  - Progestin effects in endometriosis treatment: new research on mechanisms.
AB  - New research on mechanisms of progestin effects in endometriosis treatment has
      been performed with dienogest (DNG), which has recently been launched in this
      regard. It is effective in the same low dosage of 2 mg/day, similar to the use of
      contraception and hormone therapy, whereas other progestogens (with the exception
      of dydrogesterone) must be given in much higher dosages to treat typical symptoms
      of endometriosis. This short review summarizes experimental studies on DNG. They
      demonstrate strong antiproliferative effects in endometrial and endometriotic
      cells or experimental endometriosis, as well as anti-inflammatory and
      antiangiogenic actions. By direct action on the ovarian folliculogenesis DNG lead
      to only modest suppression of estradiol production in contrast to the high-dosed
      progestogens or to gonadotropin releasing hormone (GnRH) agonists. These effects
      add to the well-known tolerability because DNG is very neutral regarding
      cardiovascular, metabolic or central action which also makes it suitable for long
      term therapy. 

PMID- 25961222
TI  - Different progestins in the treatment of endometriosis - are there relevant
      differences?
AB  - Oral progestins without an estrogen component have been described to be effective
      in the treatment of endometriosis. Several different substances have been tested,
      which are on the one hand derivatives of the natural progesterone or of the C-17
      OH-progesteron, or on the other hand derivatives of C-19-nortestosteron. Their
      common characteristic is the secretory transformation of estrogen primed uterine
      endometrium for which different dosages are necessary because of their different
      biological activities. They are different with regard to their profile and
      potency of action on hypothalamicpituitary axis, metabolic processes, breast
      tissue and genital organs. They are effectively similar with regard to
      endometriosis related complaints if sufficient doses are administered. No effects
      are noted on reduced fertility in endometriotic patients and the data are
      inconsistent concerning direct effects on the endometriotic cells. 

PMID- 25961223
TI  - Progesterone, progestins and psychosomatic health of women.
AB  - Psychosomatics as a medical perspective and discipline focuses on the interaction
      of physical and mental health in the specific life situation of a patient, taking
      into account the physical and emotional well-being, role functioning,
      satisfaction with the partner and family relationship, as well as sexual function
      and satisfaction. There are two important effects of progesterone on the combined
      physical, mental and sexual well-being of the climacteric patient. The first is
      the antiestrogenic effect of progesterone on the peripheral physical level which
      not only protects the endometrium against overstimulation but also reduces
      individual suffering from heavy bleeding, breast tension, bloating and general
      discomfort. The second effect is due to the complex action of progesterone in the
      brain. Studies using different progestins in different dosages and in different
      regimens show contradictory results. Some studies demonstrate an increase in
      depressed mood and reduced well-being while using synthetic progestins. Other
      studies, however, indicate an anxiolytic and sometimes antidepressant effect of
      progesterone and progesterone-like progestins with an improvement of emotional
      well-being and quality of life. In the individual patient, the positive or
      negative emotional and mental state can be conditioned by various pathways of
      progesterone and progestins. The antiestrogenic effect can attenuate the
      psychotropic effect of estradiol (E2) on the brain, thus reducing emotional well
      being. Progesterone interacting with many brain areas can have a mood stabilizing
      and anxiolytic effect through the action on the GABA receptor. This effect seems
      to be strongest when using natural progesterone and the effect varies
      considerably among different progestins and different dosages due to metabolic
      pathways involving the production of allopregnanolone or other metabolites. In
      conclusion, the positive anxiolytic and sedative effects of progesterone on the
      central nervous system depend on the type of progestogen, the dosage, the timing
      of application, the combination with estrogen, etc. Progesterone and progestins
      have important potential to maintain or improve the psychosomatic health of
      women. Their use must, however, be tailored to specific symptom clusters and to
      the individual's pre-existing psychosomatic health status. 

PMID- 25961224
TI  - Androgen modulation of pro-inflammatory and anti-inflammatory cytokines during
      preadipocyte differentiation.
AB  - BACKGROUND: Macrophages and adipocytes contribute to release of cytokines
      resulting in the chronic inflammatory profile of the metabolic syndrome. The
      local increase of proinflammatory cytokines impairs adipogenesis, resulting in
      formation of dysfunctional adipocytes that are unable to store and handle lipids.
      The altered lipid fluxes in/from adipocytes affect whole-body metabolism. We
      investigated the role of androgens on adipocyte-derived proinflammatory and anti
      inflammatory cytokines during preadipocyte differentiation. MATERIALS AND
      METHODS: Various differentiation methods were used to obtain full conversion of
      3T3-L1 into mature adipocytes. The degree of adipocyte conversion in the
      presence/absence of dihydrotestosterone (DHT) was analyzed by measuring
      intracellular triglycerides (Oil Red O staining). The effects of DHT
      administration on interleukin 1beta (IL-1beta), IL-2, IL-6, IL-10, IL-12,
      interferon gamma (IFNgamma) and tumor necrosis factor alpha (TNFalpha) secretion
      was measured at days 0, 4, 6 and 8 of differentiation using the SearchLight
      multiplex protein array. RESULTS: DHT regulates a number of cytokines in
      committed and mature 3T3-L1 adipocytes. IL-1beta and TNFalpha were readily
      suppressed at the very early stages of differentiation. IFNgamma release was
      inhibited at day 4, but the effect was no longer detectable on day 8. IL-6 and IL
      12 were significantly reduced at day 8 of differentiation. Conversely, the
      differentiation-dependent increase of IL-2 and IL-10 was further stimulated by
      DHT since day 0. CONCLUSIONS: We provide evidence that androgens promote an anti
      inflammatory profile that parallels the acquisition of a functional adipocyte
      phenotype. The crosstalk between androgens, adipocyte-derived mediators of
      inflammation and intracellular lipid fluxes could have profound implications on
      metabolism of men with obesity and metabolic syndrome.

PMID- 25961225
TI  - New insights into the protective effects of DHEA1).
AB  - Numerous studies investigated the effects of pharmacological doses of DHEA in
      animals. Among protective effects, antiglucocorticoid potencies, triggering and
      modulation of immunity and anticancerous effects were reported. Because DHEA
      levels decrease in aging humans, this steroid has been assayed as replacement
      therapy in elderly volunteers without striking evidence for beneficial effects.
      Examination of the investigations carried out in animals lead to suspect that,
      rather than DHEA, its metabolites produced in tissues could be responsible for
      some of the observed effects. Known as the "mother steroid", DHEA is a precursor
      for androgenic and estrogenic steroid hormones. In addition, DHEA is hydroxylated
      at the 7alpha position by the cytochrome P450 7B1 (CYP7B1), and the 7alpha
      hydroxy-DHEA produced is a substrate for the 11beta-hydroxysteroid dehydrogenase
      type 1 (11beta-HSD1) which converts it into 7beta-hydroxy-DHEA. Both 7
      hydroxylated metabolites were shown to favor the onset of immunity in mice and
      the activation of memory T cells in humans. Other DHEA and testosterone-derived
      metabolites, namely epiandrosterone and 5alpha-androstane-3beta,17beta-diol, are
      also substrates for the CYP7B1 and their 7alpha-hydroxylated products were also
      converted into the 7beta epimer by the 11beta-HSD1. When assayed at doses 104
      lower than DHEA, 7beta-hydroxy-epiandrosterone was shown to shift the
      prostaglandin metabolism patterns from prostaglandin E2 (PGE2) to PGD2
      production, thus triggering the resolution of inflammation. In addition, 7beta
      hydroxy-epiandrosterone (1 nM) exerted the same effects as tamoxifen (1 MUM) on
      the proliferation of MCF-7 and MDA-231 human breast cancer cells. These findings
      suggest that the observed effects of 7beta-hydroxy-epiandrosterone could be
      mediated by estrogen receptors. This overview of recent research implies that
      DHEA does not act directly and that its effects are due to its metabolites when
      produced in tissues. Treatments with DHEA should take into account the target
      tissue abilities to produce the desired metabolites through the two key enzymes,
      CYP7B1 and 11beta-HSD1. 

PMID- 25961226
TI  - Intravaginal DHEA, by a strictly local action, exerts beneficial effects on both
      vaginal atrophy symptoms and sexual dysfunction.
AB  - BACKGROUND: Following complete cessation of estrogen secretion by the ovaries at
      menopause, all estrogens and practically all androgens are made from
      dehydroepiandro-sterone (DHEA) of adrenal/ovarian origin. Although being an
      inactive molecule itself, DHEA is transformed at various levels and ratios into
      estrogens and/or androgens only in the tissues that possess the required cell
      specific steroidogenic enzymes with minimal or no release of the active hormones
      in the blood according to the mechanisms of intracrinology. Vaginal atrophy
      affects 50% of postmenopausal women from 50 to 60 years of age and 72% of women
      70 years and older. METHODS AND RESULTS: At the standard 12-week time interval,
      0.5% DHEA caused a 45.9+/-5.31 (p<0.0001 vs. placebo) decrease in the percentage
      of parabasal cells, a 6.8%+/-1.29% (p<0.0001 vs. placebo) increase in superficial
      cells, a 1.3+/-0.13 unit (p<0.0001 vs. placebo) decrease in vaginal pH and a
      1.5+/-0.14 score unit (p<0.0001 vs. placebo) decrease in the severity of the most
      bothersome symptom. Similar changes were observed on vaginal secretions, color,
      epithelial surface thickness and epithelial integrity. In addition to the effects
      of intravaginal DHEA on the symptoms and signs of vaginal atrophy, a time- and
      dose-dependent improvement in the four domains of sexual function was observed,
      namely desire, arousal, orgasm and pain at sexual intercourse. CONCLUSIONS: The
      present data indicate that combined androgenic/estrogenic stimulation in the
      three layers of the vagina exerts important beneficial effects on sexual function
      in women without systemic action on the brain and other extravaginal tissues.

PMID- 25961227
TI  - Testosterone deficiency in the aging male and its relationship with sexual
      dysfunction and cardiovascular diseases.
AB  - BACKGROUND: The relationship between age-associated dec-line of testosterone (T),
      cardiovascular (CV) risk and sexual dysfunction in males is not completely clear.
      The aim of the present study was to report our experience in a large series of
      patients seeking medical care for sexual dysfunction and comparing our results
      with current evidence. MATERIALS AND METHODS: Here, we review published data from
      our laboratory and reported data from a cross-sectional analysis on a consecutive
      series of 3149 patients seeking medical care at our Unit for sexual dysfunction
      (between 2000 and 2010). Among them, 1687 (studied between 2000 and 2007)
      patients were also longitudinally evaluated (mean follow-up 4.3+/-2.6 years) for
      forthcoming major cardiovascular events (MACEs). All major findings were
      discussed in comparison with data reported in the literature. RESULTS: T levels
      were associated with a wide array of biological and psychological factors, which
      substantially differ as a function of age. Some of these associations were more
      evident in the youngest patients (psychological symptoms), whereas sexual
      symptoms, including erectile function, sexual desire and the frequency of sexual
      intercourse, were associated with T levels only in the oldest patients. We did
      not find any association between T and MACEs, whereas we reported a close link
      between CV mortality and low T. Both these observations are in line with data
      obtained in community-dwelling men. CONCLUSIONS: T plays a crucial role in
      regulating different aspects of male sexual function. The effect of T on CV risk
      needs to be confirmed in larger epidemiological and interventional studies.

PMID- 25961228
TI  - Role of androgens in modulating male and female sexual function.
AB  - Advancement in basic and clinical research has provided considerable evidence
      suggesting a key role of androgens in the physiology and pathophysiology of
      sexual function. Evidence from clinical studies in men and women with androgen
      deficiency support a role of androgens in maintaining sexual function in men and
      women and are integral in maintaining sexual health. Preclinical studies
      utilizing male animal models demonstrated a role of androgens in maintenance of:
      (i) penile tissue structural integrity, (ii) penile trabecular smooth muscle
      growth and function, (iii) integrity of penile nerve fiber network, (iv)
      signaling pathways in the corpora cavernosa, (v) myogenic and adipogenic
      differentiation in the corpora cavernosa, (vi) physiological penile response to
      stimuli, and (vii) facilitating corporeal hemodynamics. These findings strongly
      suggest a role for androgen in the physiology of penile erection. In addition,
      clinical studies in hypogonadal men with erectile dysfunction treated with
      testosterone provided invaluable information on restoring erectile function and
      improving ejaculatory function. Similarly, clinical studies in surgically or
      naturally postmenopausal women with androgen deficiency suggested that androgens
      are important for maintaining sexual desire and testosterone treatment was shown
      to improve sexual desire, arousal and orgasm. Furthermore, studies in female
      animal models demonstrated that androgens maintain the integrity of vaginal nerve
      fiber network, muscularis volume, and enhance genital blood flow and
      mucification. Based on the biochemical, physiological and clinical findings from
      human and animal studies, we suggest that androgens are integral for maintaining
      sexual function and play a critical role in maintaining sexual health in men and
      women. 

PMID- 25961229
TI  - The relationship between testosterone deficiency and frailty in elderly men.
AB  - The vulnerable health status usually preceding the onset of overt disability is
      often referred to as frailty. A stringent definition is elusive but it can be
      viewed as a physiological syndrome, characterized by decreased reserve and
      diminished resistance to stressors, resulting from a cumulative decline across
      multiple physiological systems and causing vulnerability to adverse outcomes.
      Elements of frailty are related to the neurological system, metabolism, joints,
      bones, and muscles. Sarcopenia seems to be the major determinant of frailty.
      Several components of the frailty syndrome are related to loss of physiological
      actions of testosterone (T). T and/or its aromatized metabolite, estradiol, are
      necessary for maintenance of bone mineral density. Furthermore, T stimulates
      erythrocyte formation. T has a profound effect on body composition. Androgens
      promote differentiation of mesenchymal pluripotent cells into the myogenic
      lineage and inhibit differentiation into the adipogenic lineage. Skeletal muscles
      of older men are as responsive to the anabolic effects of T as of younger men.
      Thus, although frailty is obviously a complex syndrome, some elements are
      androgen-associated and these can improve in men with subnormal T levels when
      treated with T. Evidence suggests that T treatment in frail elderly men with low
      T improves body composition, quality of life, and physical function, including
      increased axial bone mineral density and body composition. The data available to
      date strongly suggest a relationship between T-deficiency and frailty and warrant
      further basic and clinical investigations to extend these observations to the
      management of elderly men with frailty. 

PMID- 25961230
TI  - Aldosterone and the cardiovascular system: a dangerous association.
AB  - Initial studies have focussed on the actions of aldosterone in renal electrolyte
      handling and, as a consequence, blood pressure control. More recently, attention
      has primarily been focussed on its actions on the heart and vascular system,
      where it is locally produced. Aldosterone by binding mineralocorticoid receptors
      causes oxidative stress, fibrosis and triggers an inflammatory response in the
      cardiovascular system. All these effects could be underlying the role of aldo
      sterone on cardiac and vascular remodelling associated with different
      pathological situations. At the vascular level, aldo-sterone affects endothelial
      function because administration of aldosterone to rats impaired endothelium
      dependent relaxations. In addition, the administration of mineralocorticoid
      receptor antagonists ameliorates endothelium-dependent relaxation in models of
      both hypertension and atherosclerosis, and in patients with heart failure.
      Several mechanisms can participate in this effect, including production of
      vasoconstrictor factors and a reduction in nitric oxide levels. This reduction
      can involve both a decrease in its production as well as an increase in its
      degradation by reactive oxygen species. Aldosterone can produce oxidative stress
      by the activation of transcription factors such as the NF-kappaB system, which
      can also trigger an inflammatory process through the production of different
      cytokines. At cardiac level, high levels of aldosterone can also adversely impact
      heart function by producing cardiac hypertrophy, diastolic dysfunction and
      electrical remodelling through changes in ionic channels. All these effects can
      explain the beneficial effect of mineralocorticoid blockade in the cardiovascular
      system. 

PMID- 25961231
TI  - Protective effect of estrogens on the brain of rats with essential and endocrine
      hypertension.
AB  - Estrogen neuroprotection has been shown in pathological conditions damaging the
      hippocampus, such as trauma, aging, neurodegeneration, excitotoxicity, oxidative
      stress, hypoglycemia, amyloid-beta peptide exposure and ischemia. Hypertensive
      encephalopathy also targets the hippocampus; therefore, hypertension seems an
      appropriate circumstance to evaluate steroid neuroprotection. Two experimental
      models of hypertension, spontaneously hypertensive rats (SHR) and
      deoxycorticosterone (DOCA)-salt hypertensive rats, develop hippocampal
      abnormalities, which include decreased neurogenesis in the dentate gyrus,
      astrogliosis, low expression of brain-derived neurotrophic factor (BDNF) and
      decreased number of neurons in the hilar region, with respect of their
      normotensive strains Wistar Kyoto (WKY) and Sprague-Dawley rats. After estradiol
      was given for 2 weeks to SHR and DOCA-treated rats, both hypertensive models
      normalized their faulty hippocampal parameters. Thus, estradiol treatment
      positively modulated neurogenesis in the dentate gyrus of the hippocampus,
      according to bromodeoxyuridine incorporation and doublecortin
      immunocytochemistry, decreased reactive astrogliosis, increased BDNF mRNA and
      protein expression in the dentate gyrus and increased neuronal number in the
      hilar region of the dentate gyrus. A role of local estrogen biosynthesis is
      suggested in SHR, because basal aromatase mRNA in the hippocampus and
      immunoreactive aromatase protein in cell processes of the dentate gyrus were
      highly expressed in these rats. Estradiol further stimulated aromatase-related
      parameters in SHR but not in WKY. These observations strongly support that a
      combination of exogenous estrogens to those locally synthesized might better
      alleviate hypertensive encephalopathy. These studies broaden estrogen
      neuroprotective functions to the hippocampus of hypertensive rat models. 

PMID- 25961232
TI  - Glucocorticoid signaling in cardiac disease.
AB  - As major mediators of stress regulation, glucocorticoids have an essential role
      in maintaining cardiovascular homeostasis under both physiological and
      pathological conditions. The release of glucocorticoids into the peripheral
      circulation is adjusted by the hypothalamic-pituitary-adrenal axis in response to
      various pathological challenges such as sepsis, starvation, and psychological
      stress. Clinically, dysregulation of the glucocorticoid-mediated signaling as a
      result of either excess ligand or receptor hypersensitivity is connected with the
      progression of unfavorable cardiovascular events such as cardiac hypertrophy,
      atherosclerosis, and coronary artery disease. The direct effects of
      glucocorticoids on cardiac tissues are mediated by two steroid receptors, the
      glucocorticoid receptor and mineralocorticoid receptor, which are both expressed
      by cardiomyocytes. Although each receptor has some shared responses to
      glucocorticoids, each receptor also has unique effects on cardiac functions.
      Elucidating the selective actions of each receptor is critical for determining
      the proper pharmaceutical targets in cardiovascular diseases. 

PMID- 25961233
TI  - Peroxisome proliferator-activated receptor beta/delta: a master regulator of
      metabolic pathways in skeletal muscle.
AB  - Skeletal muscle is considered to be a major site of energy expenditure and thus
      is important in regulating events affecting metabolic disorders. Over the years,
      both in vitro and in vivo approaches have established the role of peroxisome
      proliferator-activated receptor-beta/delta (PPARbeta/delta) in fatty acid
      metabolism and energy expenditure in skeletal muscles. Pharmacological activation
      of PPARbeta/delta by specific ligands regulates the expression of genes involved
      in lipid use, triglyceride hydrolysis, fatty acid oxidation, energy expenditure,
      and lipid efflux in muscles, in turn resulting in decreased body fat mass and
      enhanced insulin sensitivity. Both the lipid-lowering and the anti-diabetic
      effects exerted by the induction of PPARbeta/delta result in the amelioration of
      symptoms of metabolic disorders. This review summarizes the action of
      PPARbeta/delta activation in energy metabolism in skeletal muscles and also
      highlights the unexplored pathways in which it might have potential effects in
      the context of muscular disorders. Numerous preclinical studies have identified
      PPARbeta/delta as a probable potential target for therapeutic interventions.
      Although PPARbeta/delta agonists have not yet reached the market, several are
      presently being investigated in clinical trials. 

PMID- 25961234
TI  - Mechanisms of estrogen protection in diabetes and metabolic disease.
AB  - Until menopause, women are largely protected against several metabolic disorders,
      implicating a role for sex hormones. Adiposity and insulin resistance are
      fundamental features in the pathogenesis of type 2 diabetes mellitus. Emerging
      data suggest that sex-steroid hormones and adipocyte-derived hormones and
      cytokines could be associated with type 2 diabetes risk and that some of these
      novel markers can exhibit a sexual dimorphism with regard to this risk. Evidence
      suggests that the female hormone, 17beta-estradiol protects insulin production
      and prevents diabetes. Although 17beta-estradiol acts primarily via two distinct
      estrogen receptors (ERs), ERalpha and ERbeta, it appears that ERalpha protects
      beta-cell survival, whereas ERbeta reduces ERalpha function and provokes beta
      cell apoptosis. Accordingly, use of menopausal hormone therapy has been shown to
      reduce diabetes incidence and weight gain. Recent findings that benefits of
      menopausal hormone therapy might not outweigh the risks in some women do not
      negate the importance of identifying mechanisms by which 17beta-estradiol
      attenuates the development and progression of metabolic disease. This could lay
      the ground to the design of pharmacological treatments for the prevention of
      menopause-associated metabolic disorders that are safer and more efficacious than
      current hormone-based regimens. 

PMID- 25961235
TI  - The distribution of placental oxidoreductase isoforms provides different milieus
      of steroids influencing pregnancy in the maternal and fetal compartment.
AB  - Using information based on the steroid metabolome in maternal and fetal body
      fluids, we attempted to ascertain whether there is a common mechanism, which is
      based on the placental distribution of various isoforms of 17beta-hydroxysteroid
      dehydrogenases and aldo-keto reductases. This system simultaneously provides a
      higher proportion of active progestogens in fetal circulation and a higher
      proportion of active estrogens and GABAergic steroids in the maternal
      compartment. The data obtained using gas chromatography-mass spectrometry
      completely support the aforementioned hypothesis. We confirmed a common trend to
      higher ratios of steroids with hydroxy-groups in the 3alpha-, 17beta-, and
      20alpha-positions to the corresponding 3-oxo-, 17-oxo-, and 20-oxo-metabolites,
      respectively, in the maternal blood when compared with the fetal circulation, and
      the same tendency was obvious in the 3alpha-hydroxy/3beta-hydroxy steroid ratios.
      A decreasing trend was observed in the ratios of active estrogens and neuro
      inhibitory steroids to their inactive counterparts in fetal and maternal body
      fluids. This was probably associated with a limited capacity of placental
      oxidoreductases in the converting of estrone to estradiol during the
      transplacental passage. Although we observed a decreasing trend in pregnancy
      sustaining steroids with increasing gestational age, we recorded rising levels of
      estradiol and particularly of estriol, regardless of the limited capacity of
      placental oxidoreductases. Besides the estradiol, which is generally known as an
      active estrogen, estriol may be of importance for the termination of pregnancy
      with respect to its excessive concentrations near term which allows its binding
      to estrogen receptors. 

PMID- 25961236
TI  - Progesterone as a regulator of phosphorylation in the central nervous system.
AB  - Progesterone exerts a variety of actions in the central nervous system under
      physiological and pathological conditions. As in other tissues, progesterone acts
      in the brain through classical progesterone receptors and through alternative
      mechanisms. Here, we review the role of progesterone as a regulator of kinases
      and phosphatases, such as extracellular-signal regulated kinases,
      phosphoinositide 3-kinase, Akt, glycogen synthase kinase 3, protein phosphatase
      2A and phosphatase and tensin homolog deleted on chromosome 10. In addition, we
      analyzed the effects of progesterone on the phosphorylation of Tau, a protein
      that is involved in microtubule stabilization in neurons. 

PMID- 25961237
TI  - Estrogens and progestins: molecular effects on brain cells.
AB  - Sex steroids are known to regulate brain function and their role is so important
      that several diseases are strictly correlated with the onset of menopause when
      estrogen-progesterone deficiency makes neural cells much more vulnerable to toxic
      stimuli. Although in the past years several scientists have focused their studies
      on in vitro and in vivo effects of sex steroids on the brain, we are still far
      from complete knowledge. Indeed, contrasting results from large clinical trials
      have made the entire issue much more complicated. Currently we know that
      protective effects exerted by sex steroids depend on several factors among which
      the dose, the health of the cells and the type of molecule being used. In this
      review, we present an overview of the direct and indirect effects of estrogen and
      progesterone on the brain with specific focus on the molecular mechanisms by
      which these molecules act on neural cells. 

PMID- 25961238
TI  - The integration of a Stat3 specific peptide aptamer into the thioredoxin scaffold
      protein strongly enhances its inhibitory potency.
AB  - We are characterizing peptides which are able to interact with functional domains
      of oncoproteins and thus inhibit their activity. The yeast two-hybrid system was
      used to derive a peptide sequence which specifically interacts with the
      dimerization domain of the transcription factor Stat3. The activated form of
      Stat3 is required for the survival of many transformed cells and Stat3 inhibition
      can cause tumor cell death. The genetic selection of specific peptide sequences
      from random peptide libraries requires the integration into a scaffold protein
      and the expression in yeast cells. The scaffold protein, a variant of the human
      thioredoxin protein, has previously been optimized and also allows for effective
      bacterial expression of the recombinant protein and the cellular uptake of the
      purified, recombinant protein. We investigated the contributions of the scaffold
      protein to the inhibitory properties of rS3-PA. For this purpose we compared rS3
      PA in which the ligand peptide is embedded within the thioredoxin scaffold
      protein with a minimal Stat3-interacting peptide sequence. sS3-P45 is a synthetic
      peptide of 45 amino acids in length and consists only of the Stat3-binding
      sequence of 20 amino acids, a protein transduction domain (PTD) and a Flag-tag.
      Both, the recombinant rS3-PA of 19.3 kDa and the synthetic sS3-P45 of 5.1 kDa,
      were taken up into the cytoplasm of cells by the PTD-mediated transduction
      process, inhibited Stat3 target gene expression and caused the death of Stat3
      dependent tumor cells. Stat3-independent normal cells were unaffected. rS3-PA
      effectively inhibited Stat3 function at 2 MUM, however, sS3-P45 was required at a
      concentration of 100 MUM to exert the same effects. The more potent action of rS3
      PA is most probably due to a conformational stabilization of the Stat3
      interacting peptide in the context of the scaffold protein. 

PMID- 25961239
TI  - The corepressor Alien as a novel tumor suppressor?
AB  - Alien has been characterized as a corepressor for nuclear hormone receptors that
      harbor a silencing domain such as the thyroid hormone receptor (TR), the vitamin
      D3 receptor (VDR) and DAX-1. In addition, the androgen receptor (AR), a steroid
      hormone receptor, interacts with Alien. Alien enhances gene silencing mediated by
      TR, VDR and DAX-1, whereas Alien inhibits AR-mediated transactivation. The
      inhibition of AR by Alien seems to be restricted to cases where AR is bound to AR
      antagonists. In line with this, Alien inhibits AR target gene expression and
      human prostate cancer cell proliferation in an antagonist-specific manner
      indicating that Alien has an inhibitory role for cell cycle progression. Alien
      mediates gene silencing by recruitment of histone deacetylase activity and
      interestingly through nucleo-some assembly activity. Hereby, Alien enhances
      nucleosome positioning mediated by nucleosome assembly protein 1, which suggests
      a novel molecular mechanism of corepressor function. Using a proteomic approach
      to identify Alien interacting partners, we detected the cell cycle factor E2F1 to
      bind to Alien in vivo. The E2F1-mediated transactivation and E2F target gene
      expression is inhibited by Alien, and in line with this Alien is observed to
      repress cell cycle progression. 

PMID- 25961240
TI  - Androgen receptor: acting in the three-dimensional chromatin landscape of
      prostate cancer cells.
AB  - Androgen receptor (AR) acts as a hormone-controlled transcription factor that
      conveys the messages of both natural and synthetic androgens to the level of
      genes and gene programs. Defective AR signaling leads to a wide array of androgen
      insensitivity disorders, and deregulated AR function, in particular
      overexpression of AR, is involved in the growth and progression of prostate
      cancer. Classic models of AR action view AR-binding sites as upstream regulatory
      elements in gene promoters or their proximity. However, recent wider genomic
      screens indicate that AR target genes are commonly activated through very distal
      chromatin-binding sites. This highlights the importance of long-range chromatin
      regulation of transcription by the AR, shifting the focus from the linear gene
      models to three-dimensional models of AR target genes and gene programs. The
      capability of AR to regulate promoters from long distances in the chromatin is
      particularly important when evaluating the role of AR in the regulation of genes
      in malignant prostate cells that frequently show striking genomic aberrations,
      especially gene fusions. Therefore, in addition to the mechanisms of DNA loop
      formation between the enhancer bound ARs and the transcription apparatus at the
      target core promoter, the mechanisms insulating distally bound ARs from
      promiscuously making contacts and activating other than their normal target gene
      promoters are critical for proper physiological regulation and thus currently
      under intense investigation. This review discusses the current knowledge about
      the AR action in the context of gene aberrations and the three-dimensional
      chromatin landscape of prostate cancer cells. 

PMID- 25961241
TI  - Crosstalk with insulin and dependence on PI3K/Akt/mTOR rather than MAPK pathways
      in upregulation of basal growth following long-term oestrogen deprivation in
      three human breast cancer cell lines.
AB  - BACKGROUND: MCF-7, T-47-D, ZR-75-1 human breast cancer cell lines are dependent
      on oestrogen for growth but can adapt to grow during long-term oestrogen
      deprivation. This serves as a model for identification of therapeutic targets in
      endocrine-resistant breast cancer. METHODS: An overlooked complication of this
      model is that it involves more than non-addition of oestrogen, and inadequate
      attention has been given to separating molecular events associated with each of
      the culture manipulations. RESULTS: Insulin and oestradiol were shown to protect
      MCF-7 cells against upregulation of basal growth, demonstrating a crosstalk in
      the growth adaptation process. Increased phosphorylation of p44/42MAPK and c-Raf
      reflected removal of insulin from the medium and proliferation of all three cell
      lines was inhibited to a lesser extent by PD98059 and U0126 following long-term
      oestrogen/insulin withdrawal, demonstrating a reduced dependence on the MAPK
      pathway. By contrast, long-term oestrogen/insulin deprivation did not alter
      levels of phosphorylated Akt and did not alter the dose-response of growth
      inhibition with LY294002 in any of the three cell lines. The IGF1R inhibitor
      picropodophyllin inhibited growth of all MCF-7 cells but only in the long-term
      oestrogen/insulin-deprived cells was this paralleled by reduction in
      phosphorylated p70S6K, a downstream target of mTOR. Long-term oestrogen/insulin
      deprived MCF-7 cells had higher levels of phosphorylated p70S6K and developed
      increased sensitivity to growth inhibition by rapamycin. CONCLUSIONS: The greater
      sensitivity to growth inhibition by rapamycin in all three cell lines following
      long-term oestrogen/insulin deprivation suggests rapamycin-based therapies might
      be more effective in breast cancers with acquired oestrogen resistance.

PMID- 25961242
TI  - Antihormone induced compensatory signalling in breast cancer: an adverse event in
      the development of endocrine resistance.
AB  - Using MCF7 breast cancer cells, it has been shown that antihormones promote
      expression/activity of oestrogen-repressed tyrosine kinases, notably EGFR, HER2
      and Src. These inductive events confer responsiveness to targeted inhibitors
      (e.g., gefitinib, trastuzumab, saracatinib). We observed that these antihormone
      induced phenomena are common to ER+HER2- and ER+HER2+ breast cancer models in
      vitro, where targeting of EGFR, HER2 or Src alongside antihormone improves
      antitumour response and delays/prevents endocrine resistance. Such targeted
      inhibitors also subvert acquired endocrine resistant cells which retain increased
      EGFR, HER2 and Src (e.g., TAMR and FASR models derived after 6-12 months of
      tamoxifen or Faslodex treatment). Thus, antihormone-induced tyrosine kinases
      comprise "compensatory signalling" crucial in limiting maximal initial
      antihormone response and subsequently driving acquired resistance in vitro.
      However, despite such convincing preclinical findings from our group and others,
      clinical trials examining equivalent antigrowth factor strategies have proved
      relatively disappointing. Our new studies deciphering underlying causes reveal
      that further antihormone-promoted events could be pivotal in vivo. Firstly,
      Faslodex induces HER3 and HER4 which sensitise ER+ cells to heregulin, a
      paracrine growth factor that overcomes endocrine response and diminishes
      antitumour effect of agents targeting EGFR, HER2 or Src alongside antihormone.
      Secondly, extended antihormone exposure (experienced by ER+ cells prior to
      adjuvant clinical relapse) can "reprogramme" the compensatory kinase profile in
      vitro, hindering candidate antigrowth factor targeting of endocrine resistance.
      Faslodex resistant cells maintained with this antihormone for 3 years in vitro
      lose EGFR/HER2 dependency, gaining alternative mitogenic/invasion kinases.
      Deciphering these previously unrecognised antihormone-induced events could
      provide superior treatments to control endocrine relapse in the clinic. 

PMID- 25961243
TI  - The thyroid hormone receptors as tumor suppressors.
AB  - In addition to the well-known role of the thyroid hormone receptors (TRs) in
      growth, development and metabolism, there is increasing evidence that they have
      profound effects on cell proliferation and malignant transformation. TRs repress
      transcriptional induction of cyclin D1 by the ras oncogene and block
      transformation and tumor formation by Ras-transformed fibroblasts in nude mice.
      Mutant receptors that do not bind coactivators are able to display these actions,
      whereas receptors defective in corepressors binding are unable to antagonize the
      responses to the ras oncogene. Furthermore, expression of TRbeta1 in
      hepatocarcinoma and breast cancer cells abolishes anchorage-independent growth
      and migration, blocks responses to growth factors and represses expression of
      prometastatic genes, reducing tumor growth and strongly inhibiting invasiveness,
      extravasation and metastasis formation in euthyroid mice. By contrast, when cells
      are inoculated into hypothyroid host, tumor growth is retarded, but tumors are
      more invasive and metastatic growth is enhanced. Increased aggressiveness and
      tumor growth retardation was also observed with parental cells that do not
      express TRs, showing that changes secondary to hypothyroidism can modulate tumor
      progression and metastatic growth independently of the presence of TRs on the
      tumor cells. Finally, increased malignancy of skin tumors is found in mice
      lacking TRs, further demonstrating the role of these receptors as inhibitors of
      tumor progression and suggesting that they represent a potential therapeutic
      target in cancer. 

PMID- 25961245
TI  - Extending aromatase inhibitor sensitivity in hormone resistant breast cancer.
AB  - Aromatase inhibitors (AIs) are first-line treatment for ER+ breast cancer.
      However, despite responses initially, some patients can eventually acquire
      resistance. Moreover, 25% of all breast cancer patients do not express the
      estrogen receptor (ERalpha) and are innately resistance. In tumors of mouse
      models with acquired AI letrozole resistance, expression of ERalpha was reduced
      whereas HER2/growth factor signaling was enhanced. Treatment of mice with
      trastuzumab (HER2 antibody) reduced HER2/p-MAPK but restored ERalpha expression.
      The addition of trastuzumab to letrozole treatment when tumors progressed
      resulted in significantly longer tumor suppression than these drugs alone. Thus,
      inhibition of both HER2 and ERalpha signaling pathways was necessary to overcome
      resistance. In ERalpha-negative tumors, the receptor has been shown to be
      silenced by epigenetic modifications. Treatment of MDA-MB-231 ER-negative tumors
      with a histone deacetylase inhibitor, entinostat (ENT) increased expression of
      ERalpha and also aromatase. When ENT was combined with letrozole, tumor growth
      rate was markedly reduced compared with control tumors. ENT plus letrozole
      treatment also prevented the colonization and growth of MDA-MB-231 cells in the
      lung with significant reduction in visible and microscopic foci. These novel
      strategies could improve treatment for patients with acquired and innate
      resistance to AIs. 

PMID- 25961244
TI  - The role of nuclear endothelial nitric oxide synthase in the endothelial and
      prostate microenvironments.
AB  - This review is based on novel observations from our laboratory on the nuclear
      translocation and functional role of endothelial nitric oxide synthase (eNOS) in
      endothelial and prostate cancer (PCa) epithelial cells. Nitric oxide (NO), the
      product of eNOS, is a free radical involved in the physiology and pathophysiology
      of living organisms and in a variety of biological processes including the
      maintenance of vascular homeostasis. Of relevance in this context is the role
      that estrogens play in the apoptotic process and the migration of endothelial
      cells through the regulation of target genes such as eNOS itself. It has been
      shown that both estrogen and NO signaling, mediated respectively by the estrogen
      receptors (ERs) and eNOS, can strongly counteract endothelial senescence through
      a common effector, the catalytic subunit of human telomerase. Therefore, this
      protein has been identified as a key molecule in the aging process which,
      intriguingly, is considered the only risk factor in the development of PCa and
      one of the major determinants of cardiovascular diseases. Indeed, in both these
      contexts we have defined a molecular mechanism involving activation of eNOS and
      hypoxia-inducible factors in association with ERbeta that characterizes the most
      aggressive form of PCa or influences endothelial cell differentiation. Altogether
      these data led us to postulate that activation of eNOS is a crucial requirement
      for the delaying of endothelial senescence as well as for the acquisition of
      androgen-independence and for tumor progression in the prostate microenvironment.

PMID- 25961246
TI  - Benefits and risks during HRT: main safety issue breast cancer.
AB  - To assess the benefits and risks during hormone replacement therapy (HRT) in
      postmenopausal women, the only placebo-controlled study testing clinical
      endpoints with high statistical power has been the Women's Health Initiative
      (WHI). Although this trial, conducted mainly in older high-risk women, might not
      reflect the practical conditions for the normal use of HRT, the WHI for the first
      time provides the main risks in relative as well as in absolute numbers, which
      are venous thromboembolism and breast cancer, and in older women also myocardial
      infarction and stroke. Proven benefits such as treatment of climacteric symptoms,
      reduction of osteoporotic fractures and decrease of colon cancer risk seem to be
      only important for younger women, because only with early start of HRT
      cardiovascular risks can be reduced. Reduction of cardiovascular risks can be
      achieved using transdermal HRT, which, however, was not tested in a placebo
      controlled study design similar to that in the WHI. This review focuses on the
      results of the WHI, comparing different age groups, and in general especially on
      the main fear of women, risk of breast cancer, which has been defined as a
      special project between two universities, a close collaboration of a German and
      Chinese research group. 

PMID- 25961247
TI  - The antihormonal preventive therapy of breast cancer and prostate cancer.
AB  - With the continuing increase of median life expectancy of important segments of
      the world's population, cancer incidence, as well as cancer related morbidity and
      mortality, are constantly increasing, especially for developing countries and for
      breast and prostate cancer, the predominant gender-associated cancer types. In
      addition to continuing, with more and more expensive efforts to develop new and
      more effective cancer treatments, it is health-politically and medico
      professionally important to realise that only successful approaches to primary
      cancer prevention of major and frequent cancer types will be able to change this
      socially and economically unfavourably outlook. It is therefore encouraging to
      see that primary (or pharmacologic, interventional) cancer prevention programs
      have been successfully developed over the past decade for individuals at elevated
      risk for breast and prostate cancer on the basis of several scientifically well
      conducted, prospective chemoprevention trials, mainly with synthetic anti
      hormones (anti-estrogens and anti-androgens) in the USA, in Europe and Australia.
      This paper summarises the presently published results and design of several
      completed and some currently running primary cancer prevention trials in breast
      cancer and prostate cancer, and also points to the important obstacles for their
      conduct and translation into general practice in the broader populations at risk
      outside of clinical prevention research. 

PMID- 25961248
TI  - A new concept of endometriosis and adenomyosis: tissue injury and repair (TIAR).
AB  - Pelvic endometriosis, deeply infiltrating endometriosis and uterine adenomyosis
      share a common pathophysiology and may be integrated into the physiological
      mechanism and new nosological concept of 'tissue injury and repair' (TIAR) and
      may, in this context, just represent the extreme of a basically physiological,
      estrogen-related mechanism that is pathologically exaggerated in an extremely
      estrogen-sensitive reproductive organ. The acronym TIAR describes a fundamental
      and apparently ubiquitous biological system that becomes operative in mesenchymal
      tissues following tissue injury and, upon activation, results in the local
      production of estradiol. Endometriosis and adenomyosis are caused by trauma. In
      the spontaneously developing disease, chronic uterine peristaltic activity or
      phases of hyperperistalsis induce, at the endometrial-myometrial interface near
      the fundo-cornual raphe, microtraumatisations, with activation of the TIAR
      mechanism. With ongoing traumatisations, such sites of inflammation might
      accumulate and the increasingly produced estrogens interfere in a paracrine
      fashion with ovarian control over uterine peristaltic activity, resulting in
      permanent hyperperistalsis and a self-perpetuation of the disease process. Overt
      autotraumatisation of the uterus with dislocation of fragments of basal
      endometrium into the peritoneal cavity and infiltration of basal endometrium into
      the depth of the myometrial wall ensues. In most cases of
      endometriosis/adenomyosis a causal event early in the reproductive period of life
      must be postulated, rapidly leading to archimetral hyperestrogenism and uterine
      hyperperistalsis. In late premenopausal adenomyosis such an event might not have
      occurred. However, as indicated by the high prevalence of the disease, it appears
      to be unavoidable that, with time, chronic normoperistalsis throughout the
      reproductive period of life accumulates to the same extent of
      microtraumatisation. With activation of the TIAR mechanism followed by chronic
      inflammation and infiltrative growth, endometriosis/adenomyosis of the younger
      woman and premenopausal adenomyosis share in principal the same pathophysiology. 

PMID- 25961249
TI  - Sex steroids in uterine endometrial cancers.
AB  - Some uterine endometrial cancers conserve estrogen dependency in advancement.
      However, the concept of advancement in tumor is complicated, because it involves
      simple growth in primary tumor and secondary spreading. The expression manner of
      estrogen receptor alpha exon 5 splicing variant, ER beta, progesterone receptor-A
      (N-terminus deletion mutant) is associated with metastatic potential in uterine
      endometrial cancers. Increased estrogen-related receptor alpha expression is
      related to tumor advancement with the loss of estrogen dependency. Steroid
      receptor coactivator-3 contributes to tumor progression and can be used as a
      treatment target for advanced uterine endometrial cancers. Estrogen responsive
      oncogenes, c-jun and c-Ha-ras, are not modi-fied by progestin in uterine
      endometrial cancer cells and are considered to be an instinct phenotype as such
      cancers. By contrast, metastatic potential of estrogen-dependent uterine
      endometrial cancers can be partially controlled by progestin via metastasis
      related genes, E-cadherin/catenins, plasminogen activator inhibitor-1, vascular
      endothelial growth factor. Thus, sex steroids related phenomena are impress-ive
      in the advancement of uterine endometrial cancers. 

PMID- 25961250
TI  - Estrogen signalling through amphiregulin may be implicated in human
      hepatocellular carcinoma.
AB  - BACKGROUND: We investigated aromatase (Aro)-driven estrogen formation in non
      tumoral and malignant liver tissues and cells, also in relation to expression of
      the estrogen receptors alpha and beta (ERalpha and ERbeta) and amphiregulin
      (AREG), aiming to gain insights into the potential role of estrogens in human
      hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Chromatographic and
      reverse transcriptase polymerase chain reaction (RT-PCR) analyses were used to
      assess activity and expression of the Aro enzyme and AREG as well as the
      expression of wild-type and variant ERs, both in vivo and in vitro. RESULTS:
      Following 24 h and 72 h incubation of liver tissues or cells with testosterone,
      human HCC tissues and HepG2 hepatoma cells showed elevated Aro activity (estrogen
      formation, respectively, of 20% and 52%-99%). By contrast, no Aro activity could
      be detected in non-tumoral tissues and HA22T liver cancer cells. Cirrhotic
      samples and Huh7 cells exhibited intermediate enzyme activity, with estrogen
      formation of 4% and 34%, respectively. Markedly lower or undetectable Aro mRNA
      levels were observed in HA22T cells and non-tumoral liver tissues compared with
      HepG2 cells and HCC samples. Cirrhotic specimens displayed variable transcript
      levels. Interestingly, no or low expression of wild-type ERalpha and ERbeta could
      be observed in liver cancer cells and malignant tissues. However, ubiquitous
      expression of the hERalpha46 variant and occasional expression of the hERbeta2/Cx
      variant were observed in cancer tissues and cells. CONCLUSIONS: It is noteworthy
      that the pattern of wild-type ERalpha was inversely related to Aro, whilst AREG
      expression was consistently associated with that of Aro. This combined evidence
      suggests that locally elevated Aro activity may increase malignant cell
      proliferation also through AREG signalling.

PMID- 25961251
TI  - Assessment of steroidogenic pathways that do not require testosterone as
      intermediate.
AB  - Traditional literature and textbooks generally describe that estradiol (E2) and
      dihydrotestosterone (DHT) are synthesized from the aromatization and 5alpha
      reduction of testosterone (T), respectively, following a pathway in which T is an
      essential intermediate (Tpath). This pathway implies that the steps of
      aromatization and 5alpha-reduction follow the reaction of the androgenic 17beta
      hydroxysteroid dehydrogenase (17beta-HSD) that catalyzes the conversion of 4
      androstenedione (4-dione) into T, and that estrogenic 17beta-HSDs are not
      required. Contrary to this belief, the cloning of many estrogen-specific 17beta
      HSDs and the observation of higher affinity of aromatase and 5alpha-reductase for
      4-dione than T are strongly in favor of biosynthetic pathways in which the steps
      catalyzed by aromatase and 5alpha-reductase precede that catalyzed by 17beta
      HSDs. Such pathways do not require T as an intermediate, as demonstrated by
      experiments using [14C]-labeled DHEA and 4-dione as substrates and incubation
      with SZ95 sebaceous gland, DU-145 prostate cancer and JEG-3 choriocarcinoma cell
      lines cultured in the presence of inhibitors of 5alpha-reductase and aromatase. A
      review of early literature about patients with testicular 17beta-HSD deficiency
      and of steroid metabolism appears to confirm the physiological functionality of
      the E2 and DHT biosynthetic pathway not requiring T as intermediate (noTpath). 

PMID- 25961252
TI  - Progesterone and cortisol levels in sporadic amyotrophic lateral sclerosis
      (sALS): correlation with prognostic factors.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder. Worse
      prognostic factors in ALS are: (a) advanced age, (b) bulbar onset, and (c) short
      time between onset and diagnosis. Progesterone (PROG) has been associated with
      neuroprotective and promyelinating activities in injury, ischemia and
      degeneration of the central and peripheral nervous system. Cortisol is connected
      to the response to stress situations and could contribute to neuronal damage. The
      goals of this study were: (i) to investigate whether PROG levels are modified by
      ALS prognostic factors and (ii) to determine whether cortisol follows the same
      pattern. We determined serum steroid levels in 27 patients with sporadic ALS
      (sALS) and 21 controls. Both steroid hormones showed significantly increased
      levels in ALS patients versus controls (mean+/-SEM: PROG ALS vs. CONTROL: 0.54+/
      0.05 vs. 0.39+/-0.04 ng/mL, p<0.05; cortisol ALS vs. CONTROL: 17.02+/-1.60 vs.
      11.83+/-1.38 MUg/dL, p<0.05).1 A trend towards higher levels of PROG were
      demonstrated in spinal onset patients compared with bulbar onset (p=0.07),
      positive correlation with survival time (RRho=0.43, p=0.04) and a trend towards
      significance with time to diagnosis (RRho=0.36, p=0.06). These correlations have
      not been demonstrated for cortisol. Elevated serum steroid levels in sALS were
      probably due to hyperfunction of the hypothalamic-pituitary-adrenal axis.
      However, only PROG correlated with better prognostic factors. Future studies will
      determine if the different behavior of PROG and cortisol relate to any particular
      role they might play during the course of this motor neuron degenerative disease.

PMID- 25961253
TI  - Circulating steroid hormones in prostate carcinogenesis. Part 2: Estrogens.
AB  - The aim of this review is to describe the associations between circulating plasma
      estrogens and prostate cancer (PCa). We recall the origins of estrogens, which
      derive from the aromatization of androgens, but also by sulfatase hydrolysis of
      estrone sulfate (E1-S), the main circulating plasma estrogen. We evoke that the
      carcinogenic effects of estrogens were demonstrated in the rat and murine
      prostate when estrogens and androgens were simultaneously administered to them.
      We also describe estrogen proliferative activity and the genotoxicity of estrogen
      hydroxylated metabolites with the formation of DNA adducts. We report published
      aromatase and CYP1B1 polymorphisms found in men with PCa. We published a
      bibliography on the relation between PCa and prostate inflammation, as well as
      the possible role of obesity in the aggressiveness of PCa. In this review, we
      provide an exhaustive list of assays carried out in subjects at high risk for PCa
      compared with Caucasians, showing that higher estrogen levels were found in the
      plasma of these subjects at high risk for PCa. Plasma estrone was the estrogen
      for which plasma concentration was highest in subjects of African descent. We
      recall the links observed between plasma estrogens, particularly E1-S, and PCa
      aggressiveness. Finally, we describe assays for determining hydroxylated
      estrogens and DNA adducts in the urine of men with PCa. We insist on the
      importance of the technology employed in estrogen measurement and propose the use
      of mass spectrometry methods to carry out estrogen assays, in order to decrease
      variability in the results of plasma estrogen assays. 

PMID- 25961254
TI  - New insight on a possible mechanism of progestogens in terms of breast cancer
      risk.
AB  - OBJECTIVES: Progestogens influence mammary gland development and probably breast
      cancer tumorigenesis by regulating a broad spectrum of physiological processes.
      We investigated receptor membrane-initiated actions of progestogens in MCF-7
      breast cancer cells overexpressing progesterone receptor membrane component 1
      (PGRMC1). DESIGN: MCF-7 cells were stably transfected with PGRMC1 expression
      plasmid (MCF-7/PGRMC1-3HA) and overexpression of PGRMC1 was verified by immune
      fluorescent analysis and Western blot. To test the effects of progestogens on
      cell proliferation, MCF-7 and MCF-7/PGRMC1-3HA cells were stimulated with a
      membrane-impermeable progesterone: BSA-fluorescein-isothiocyanate conjugate (P4
      BSA-FITC), unconjugated progesterone (P4), medroxyprogesterone acetate (MPA),
      norethisterone (NET) and drospirenone (DRSP). Furthermore, reverse phase protein
      technology was applied to identify modified downstream signaling. RESULTS:
      Progesterone did not elicit any proliferative effect on MCF-7/PGRMC1-3HA cells.
      By contrast, P4-BSA-FITC, DRSP, MPA and NET significantly triggered proliferation
      of MCF-7/PGRMC1-3HA cells, the effect being more pronounced for NET. Almost no
      effect of progestogens on proliferation was observed in MCF-7 cells. In MCF
      7/PGRMC1-3HA cells, expression of Erk1/2 was significantly reduced by 40%
      compared to MCF-7 cells. CONCLUSIONS: Our data indicate that PGRMC1 mediates a
      progestogen-dependent proliferative signal in MCF-7 cells. Of significant
      interest is that progesterone and synthetic progestins that are used for hormone
      therapy are different in their proliferative effects on MCF-7 and MCF-7/PGRMC1
      3HA cells. Progesterone appears to act neutrally, whereas MPA, NET and DRSP
      trigger proliferation and thus might increase breast cancer risk. The data
      presented are very important in terms of the positive results of progestogens and
      breast cancer risk in clinical studies so far.

PMID- 25961255
TI  - Age, obesity and inflammation at baseline predict the effects of testosterone
      administration on the metabolic syndrome.
AB  - BACKGROUND: Testosterone administration to hypogonadal men improves the metabolic
      syndrome. This study analyzed whether age, serum testosterone, body mass
      index/waist circumference, increment in testosterone values and C-reactive
      protein (CRP) predicted the outcome of testosterone administration. MATERIALS AND
      METHODS: A total of 110 mainly elderly men, aged between 18 and 83 years (mean+/
      SD=59.6+/-8.0) with baseline serum testosterone of 5.8-12.1 nmol/L (mean+/
      SD=9.3+/-1.7) (n>14.0 nmol/L), received parenteral testosterone undecanoate
      whereupon serum testosterone normalized between 3 and 24 months. RESULTS: (i) The
      lower the baseline testosterone, the stronger the decreases in waist size and
      triglycerides. (ii) The greater the increment in serum testosterone, the stronger
      the decreases in low-density lipoprotein (LDL) cholesterol, triglycerides and
      glucose. (iii) Older age was associated with stronger beneficial effects on waist
      size, glucose and all lipids, but a small negative effect on high-density
      lipoprotein cholesterol. (iv) Obese men and men with the largest waist
      circumference showed the strongest declines over 2 years in weight, waist
      circumference and body mass index (BMI), and also in total cholesterol,
      triglycerides and glucose. Baseline BMI predicted a stronger decline in LDL
      cholesterol, but a smaller decline in CRP levels. (v) Higher baseline CRP
      predicted larger declines in levels of triglycerides, glucose and CRP. (vi) In
      the multivariate model, age, BMI and CRP were independent predictors of the
      strongest benefit of testosterone treatment on the metabolic syndrome.
      CONCLUSIONS: Older men, particularly when obese with chronic low-grade
      inflammation benefited most of normalizing their testosterone levels, preferably
      if they reached mid-normal reference values.

PMID- 25961256
TI  - Design and synthesis of substrate mimetics based on an indole scaffold: potential
      inhibitors of 17beta-HSD type 1.
AB  - BACKGROUND: Human 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) acts
      at a pre-receptor level. It catalyzes NADPH-dependent reduction of the weak
      estrogen estrone into the most potent estrogen estradiol, which exerts its
      proliferative effects via estrogen receptors. Overexpression of 17beta-HSD1 in
      estrogen-responsive tissues is related to the development of hormone-dependent
      diseases, such as breast cancer and endometriosis. 17beta-HSD1 thus represents an
      attractive target for development of new drugs. METHODS: We designed and
      synthesized a series of 3-, 5- and 6-phenyl indole derivatives as mimetics of the
      steroid substrate estrone. All of these compounds were evaluated for inhibition
      of recombinant human 17beta-HSD1 from Escherichia coli, at concentrations of 0.6
      MUM and 6.0 MUM. RESULTS: Among 14 indole derivatives, compound 9 was an initial
      hit inhibitor of 17beta-HSD1, with moderate inhibition (64% at 6 MUM). Molecular
      docking into the crystal structure of 17beta-HSD1 (1A27) revealed that this 5
      phenyl indole derivative binds to 17beta-HSD1 similarly to co-crystalized E2.
      Compound 9 forms two H-bonds with 17beta-HSD1: one between the indole nitrogen
      and His222, and the second between the phenolic OH group and catalytic Tyr155.
      CONCLUSIONS: The indole scaffold is one of the possible starting points for the
      design of substrate mimetics of the steroid substrate estrone. Our study shows
      that these 6- and, especially, 5-phenol indole derivatives can act as moderate
      inhibitors of 17beta-HSD1. Based on inhibition assays and docking simulations, we
      can infer further improvements of the 5-phenol indole derivatives that might
      result in better inhibition profiles.

PMID- 25961257
TI  - Effect of drospirenone on proliferation of human benign and cancerous epithelial
      breast cells.
AB  - BACKGROUND: Proliferation of human breast epithelial cells is regulated by sex
      hormones. Epidemiological studies indicate that progestogen addition to estrogen
      therapy can increase breast cancer risk. However, it remains unclear if all
      progestogens react in a similar manner. Here, the new progestogen drospirenone
      (DRSP) was compared to progesterone and other synthetic progestins. DESIGN AND
      METHODS: Human benign epithelial breast cells (HMECs) were incubated for 7 days
      with DRSP, progesterone (P), medroxyprogesterone acetate (MPA) and levonorgestrel
      (LNG) in the presence of a growth factor mixture (GF). HCC1500 and T-47D cells
      (human estrogen and progesterone receptor-positive primary breast cancer cells)
      were also incubated with the progestogens, but in the presence of estradiol (E2).
      The proliferation rate was measured by the MTT assay. RESULTS: DRSP and P
      elicited a similar significant inhibition of proliferation of HMECs in
      combination with GFs. LNG and MPA had no effect. DRSP, P, MPA and LNG were able
      to significantly inhibit the proliferation of HCC1500 and T-47D cells in
      combination with E2. No significant difference between the progestogens was
      observed in HCC1500 cells, whereas in T-47D cells both DRSP and P were
      significantly more effective at 10 MUM than LNG and MPA. CONCLUSION: Because
      different results were found in the same experimental model, it appears that
      progestogens do not react similarly on the proliferation of human breast
      epithelial cells. However, for assessment of breast cancer risk different models
      should be used, because various mechanism(s) might be involved. It is also
      important to use benign as well as cancerous cell lines. The choice of
      progestogen could be of significance in terms of breast cancer risk under hormone
      therapy.

PMID- 25961258
TI  - Liposomal trichostatin A: therapeutic potential in hormone-dependent and 
      independent breast cancer xenograft models.
AB  - BACKGROUND: Trichostatin A (TSA) is one of the most potent histone deacetylase
      inhibitors (HDACi) in vitro but it lacks biological activity in vivo when
      injected intravenously owing to its fast metabolism. MATERIALS AND METHODS: TSA
      was incorporated into Stealth(r) liposomes (TSA-lipo) at a high loading and its
      anticancer activity was evaluated in several types of breast cancer cells and
      xenografts. RESULTS: In estrogen receptor alpha (ERalpha)-positive MCF-7 and T47
      D cells, TSA induced a long-term degradation of cyclin A and a proteasome
      dependent loss of ERalpha and cyclin D1, allowed derepression of p21WAF1/CIP1,
      HDAC1 and RhoB GTPase, concomitantly with blockade in G2/M of the cell cycle and
      apoptosis induction. In MDA-MB-231 (MDA) and SKBr-3 cells, TSA increased ERalpha
      mRNA and p21WAF1/CIP1 protein expression, but decreased cyclin A with a G2/M
      blockade and cleavage of polyADP-ribose polymerase (PARP). No significant
      restoration of any ER protein was noticed in any cells. TSA-lipo markedly
      inhibited tumor growth in MCF-7 and MDA cells xenografts following intravenous
      injection. Their anticancer effects were characterized by inhibition of Ki-67
      labeling, the inhibition of tumor vasculature and an increase of p21WAF1/CIP1 in
      both tumors. In MCF-7 cell tumors, enhanced RhoB accumulation in the cytoplasm of
      epithelial cells was noticed, inversely to ERalpha that was strongly decreased.
      CONCLUSION: Such anticancer activity of TSA-lipo is exp-lained by the protection
      provided by HDACi encapsulation and by the strong tumor accumulation of the
      nanocarriers as revealed by fluorescence confocal microscopy experi-ments.
      Together with its lack of toxicity, the enhanced stability of TSA-lipo in vivo
      justifies its development for therapeutic use in the treatment estradiol
      dependent and -independent breast cancers.

PMID- 25961259
TI  - Altered levels of circulating GABAergic 5alpha/beta-reduced pregnane and
      androstane steroids in schizophrenic men.
AB  - The role of GABAergic pathways in the pathophysiology of schizophrenia is
      generally accepted. Therefore, the information concerning alterations of the
      steroid metabolome associated with the disease and/or its treatment is of
      interest with regard to the pathophysiology of the disease. Hence, we assessed 18
      serum steroids and steroid polar conjugates in a group of drug-naive patients (13
      adult men) and after 6-months therapy by atypical antipsychotics and age-matched
      controls (19 men) using gas chromatography-mass spectrometry analysis. This
      study, for the first time, demonstrates the altered circulating GABAergic
      steroids in schizophrenic men as well as the effect of the therapy with two types
      of atypical antipsychotics. The GABAergic androsterone (3alpha5alpha) and
      etiocholanolone (3alpha5beta) are reduced in schizophrenic men but the therapy
      with atypical antipsychotics reinstates their levels. This reinstatement could be
      of importance when considering that the GABAergic substances generally improve
      the well-being of patients. In addition to the unconjugated androsterone, being
      the most abundant GABAergic steroid in men, most of the other GABAergic steroids
      also tended to decrease in the patients. By contrast, the conjugated 5beta
      pregnanolone isomers were elevated in the patients. In conclusion, although
      schizophrenia status in adult men is associated with unfavorable alterations in
      neuroactive steroids, the treatment with antipsychotics could at least partly
      reinstate their circulating levels. 

PMID- 25961260
TI  - Pharmacokinetics, tolerability and cycle control of three transdermal
      contraceptive delivery systems containing different doses of ethinylestradiol and
      levonorgestrel.
AB  - BACKGROUND: The only available contraceptive patch, Ortho Evra(r), delivers a
      relatively high dose of estrogen. MATERIALS AND METHODS: Three transdermal
      contraceptive delivery systems (TCDS) containing low doses of ethinylestradiol
      (EE) and levonorgestrel (LNG) were evaluated in two open-label randomized trials.
      In a phase 1, two-period, cross-over trial, AG200-12.5 and AG200LE were compared
      with a 150 MUg LNG/30 MUg EE oral contraceptive (OC) (Levlen(r)) in 39 women. In
      a phase 2, parallel-group, multicenter, three-cycle study, AG200LE, AG200-12.5
      and a higher-dose formulation, AG200-15, were evaluated in 123 women. RESULTS: In
      Study 1, mean steady-state plasma concentrations (Css, pg/mL) for the TCDS were
      17 pg/mL to 26 pg/mL for EE and 1117 pg/mL to 1505 pg/mL for LNG (for AG200LE and
      AG200-12.5 respectively). Maximum concentration (Cmax) and Css for both analytes
      were significantly lower than for Levlen. In both studies, the Css levels for EE
      and LNG in all groups were within the ranges reported for low-dose OCs. Cycle
      control for AG200-15, assessed by breakthrough bleeding and spotting episodes as
      well as number of days of unscheduled bleeding and/or spotting, was similar to
      that reported for low-dose OCs. Most adverse events were considered mild to
      moderate in intensity. The incidence of patches falling off was <2%. CONCLUSIONS:
      All three patches exhibited excellent safety and wearability profiles while
      maintaining plasma drug levels required for ovulation suppression and adequate
      cycle control. A slight increase in the EE dose in AG200-15 still places this
      TCDS within the range of low-dose OCs, with EE exposure much lower than reported
      for Ortho Evra. AG200-15 was selected for further testing in phase 3 studies.

PMID- 25961261
TI  - Human chorionic gonadotropin and a 15 amino acid hCG fragment of the hormone
      induce downregulation of the cytokine IL-8 receptor in normal breast epithelial
      cells.
AB  - Cytokine receptors are associated with tumor cell growth by increasing
      proliferation, metastasis and regulating self-renewal of cancer stem cells (SCs).
      There is a strong association between cytokine IL-8 receptor (CXCR1) over
      expression and cells displaying SC characteristics. Human chorionic gonadotropin
      (hCG) causes differentiation, inhibition of cell proliferation and increased
      apoptosis of the breast epithelium. hCG receptor (LHCGR) expression in breast
      tumors and in breast cancer cell lines is undetectable or low. In this study, our
      objective was to assess and compare the effects of hCG and a 15 amino acid hCG
      fragment of the hormone on mRNA expression of CXCR1 and LHCGR on normal breast
      epithelial cells (MCF-10F) by real time RT-PCR after treatment with hCG or a hCG
      fragment for 15 days. Cell proliferation was also measured. hCG and the hCG
      fragment decreased cell proliferation in both groups. The compounds upregulated
      LHCGR expression and downregulated CXCR1 expression. It is possible to postulate
      that an increase of LHCGR mRNA seems to respond to the decrease of CXCR1
      expression. These genes probably act synergistically to reduce the amount of
      cancer SCs in the mammary gland. Thereby, the use of hCG or the hCG fragment as a
      therapeutic or preventive tool should be considered. 

PMID- 25961262
TI  - CYP2D6 genotyping in breast cancer patients by liquid chromatography-electrospray
      ionization mass spectrometry.
AB  - The application of cytochrome P450 2D6 (CYP2D6) genotyping to allow a
      personalized treatment approach for breast cancer patients undergoing endocrine
      therapy has been repeatedly discussed. However, the actual clinical relevance of
      the CYP2D6 genotype in the endocrine treatment of breast cancer still remains to
      be elucidated. A major prerequisite for the successful and valid evaluation of
      the CYP2D6 genotype with regard to its pharmacokinetic and clinical relevance is
      the availability of a comprehensive, accurate and cost-effective CYP2D6
      genotyping strategy. Herein we present a CYP2D6 genotyping assay employing
      polymerase chain reaction (PCR)-ion pair reversed-phase high-performance liquid
      chromatography-electrospray ionization time-of-flight mass spectrometry (ICEMS).
      The genotyping strategy involves the simultaneous amplification of nine variable
      regions within the CYP2D6 gene by a two-step PCR protocol and the direct analysis
      of the generated PCR amplicons by ICEMS. The nucleotide composition profiles
      generated by ICEMS enable the differentiation of 37 of the 80 reported CYP2D6
      alleles. The assay was applied to type the CYP2D6 gene in 199 Austrian
      individuals including 106 breast cancer patients undergoing tamoxifen treatment.
      The developed method turned out to be a highly applicable, robust and cost
      effective approach, enabling an economical CYP2D6 testing for large patient
      cohorts. 

PMID- 25961263
TI  - Sildenafil protects human mammary epithelial cells against ROS production induced
      by estradiol.
AB  - Several studies suggest that xanthine dehydrogenase (XDH) and its oxidase form
      (XO) play an important role in various types of ischemic and vascular injuries.
      Recently, we have demonstrated that estradiol (E2) induces a significant decrease
      of the expression and activity of XDH and of its conversion to XO in human
      mammary epithelial cells. E2 is known to induce upregulation of eNOS gene
      expression in aortic endothelial cells. Because the XO-derived O2.- combines with
      .NO to yield ONOO-, and considering that ONOO- converts XDH to XO, the resulting
      increase of XO activity and reactive oxygen species production would eventually
      lead to a further increase of ONOO- production, thus creating a vicious cycle of
      oxidative stress. Our previous study has indicated that sildenafil has a
      protective effect on human mammary epithelial cells as a consequence of XO
      inhibition and of the resulting decrease of free oxygen radicals that can impair
      the expression of NADPH oxidase and type 5 phosphodiesterase (PDE-5). In the
      present study, we report that the dual inhibitory effect exerted by sildenafil on
      both XO and PDE-5 is a consequence of a structural modification induced by O2.-,
      also consisting of the release of a piperazine group that could in turn inhibit
      the XO enzyme. 

PMID- 25961264
TI  - Cigarette smoking and progesterone and androgen metabolites in premenopausal
      women.
AB  - BACKGROUND: Smoking represents the most widespread substance dependence in the
      world. Several studies show nicotine's ability to alter women hormonal
      homeostasis. Women smokers have higher testosterone and lower estradiol levels
      throughout life compared to women non-smokers. This negatively affects women's
      reproductive function. Furthermore, alteration of neuroactive and neuroprotective
      steroids occurs in women smokers, and this plays an important role in the
      activity of the central nervous system, cognition, mental condition, and degree
      of substance dependence. METHODS: We monitored the effect of smoking
      discontinuation on steroid spectrum in 40 premenopausal women heavy smokers.
      These women were examined before they began to discontinue smoking, and after 6,
      12, 24 and 48 weeks of abstinence. In each examination, blood was collected to
      determine steroid spectrum, LH, FSH, and SHBG; basic anthropometric data were
      also measured using GC-MS or immunoanalysis. Repeated-measures analysis of
      variance (ANOVA) model was used for evaluation of the data. RESULTS: Given the
      small number of women who persisted in not smoking, only the data after 6 weeks
      could be analyzed. No changes were found in C21 steroids, and a slight increase
      in androgens occurred after the discontinuation of smoking. CONCLUSION: Chronic
      smoking causes hyperandrogenism in fertile women; after smoking discontinuation,
      it increases further. Longer-term monitoring is necessary to show the effect of
      smoking discontinuation on steroid spectrum.

PMID- 25961265
TI  - Sodium butyrate induces cellular senescence in neuroblastoma and prostate cancer
      cells.
AB  - Cellular senescence leads to an irreversible block of cellular division capacity
      both in cell culture and in vivo. The induction of an irreversible cell cycle
      arrest is very useful for treatment of cancer. Histone deacetylases (HDACs) are
      considered as therapeutic targets to treat cancer patients. HDAC inhibitors
      repress cancer growth and are used in various clinical trials. Here, we analyzed
      whether sodium butyrate (NaBu), an inhibitor of class I and II HDACs, induces
      cellular senescence in neuroblastoma and prostate cancer (PCa) including an
      androgen-dependent as well as an androgen-independent human PCa cell line. We
      found that the HDAC inhibitors NaBu and valproic acid (VPA) induce cellular
      senescence in tumor cells. Interestingly, also an inhibitor of SIRT1, a class
      HDAC III, induces cellular senescence. Both neuroblastoma and human prostate
      cancer cell lines express senescence markers, such as the Senescence Associated
      beta-galactosidase (SA-beta-Gal) and Senescence Associated Heterochromatin Foci
      (SAHF). Furthermore, NaBu down-regulates the proto-oncogenes c-Myc, Cyclin D1 and
      E2F1 mRNA levels. The mRNA level of the cell cycle inhibitor p16 remains
      unchanged whereas that of the tumor suppressor p21 is strongly up-regulated.
      Interestingly, NaBu treatment robustly increases reactive oxygen species (ROS)
      levels. These results indicate an epigenetic regulation and an association of
      HDAC inhibition and ROS production with cellular senescence. The data underline
      that tumor cells can be driven towards cellular senescence by HDAC inhibitors,
      which may further arise as a potent possibility for tumor suppression. 

PMID- 25961266
TI  - Investigating and critically appraising the expression and potential role of
      androgen receptor in breast carcinoma.
AB  - The potential role of the androgen receptor (AR) as a predictive or prognostic
      factor in breast cancer remains unclear. We aimed to determine the prognostic
      significance of AR in a cohort of breast carcinomas with long-term follow-up and
      to critically appraise this in the context of existing literature. Four hundred
      and eight cases of invasive breast cancer were incorporated into tissue
      microarrays (TMAs). All received tamoxifen and comprised 108 cases which relapsed
      and 300 cases which did not. Mean follow-up time for the former was 84 months
      (range 1-142, SD 38.8) and for the latter was 77 months (range 11-229, SD 49.7).
      TMAs were immunohistochemically stained with AR and scored as a continuous
      variable and using the Allred score. AR expression was significantly associated
      with grade, recurrence on tamoxifen, non-breast cancer death estrogen receptor
      alpha (ERalpha) and progesterone receptor (PR). AR correlated significantly with
      better overall survival (OS) and disease-free survival (DFS) using an Allred cut
      off of 4 (log rank=0.0053 and 0.0044, respectively), and 20% positive tumor cells
      (log rank=0.0027 and 0.0059, respectively). AR expression was additionally
      associated with a reduced risk of recurrence following endocrine therapy. In
      summary, AR positive breast tumors have better OS and DFS and are less likely to
      recur following endocrine treatment. 

PMID- 25961267
TI  - Synthesis of a 19-(O-carboxymethyl)oxime hapten of 7beta-hydroxy-epiandrosterone.
AB  - In order to develop an immunoassay of 7beta-hydroxy-epiandrosterone, a
      stereoselective synthesis of a specific hapten, 7beta-hydroxy-19-oxo-androstan 19
      (O-carboxymethyl)oxime (17), was performed. This synthesis was achieved in 16%
      overall yield starting from the well-known 3beta-acetoxy-19-hydroxy-5-androsten
      17-one (1). After coupling of the alkyl oxime moiety, an allylic oxidation of the
      C-7 carbon under mild conditions followed by two selective reductions established
      all the functionalities of the final compound 17. 

PMID- 25961268
TI  - Method for regeneration of hormones: 17beta-estradiol, 21alpha
      hydroxyprogesterone and corticosterone. A pathway for a possible medical
      application.
AB  - The hormones 17beta-estradiol (17betaE2), 21alpha-hydroxyprogesterone (21alpha
      HOPRG) and corticosterone (CORT) were used as representative models for the
      study. As a source for hormone excitation in singlet state serviced monochromatic
      UV-light (lambda=254 nm), it was stated that the transients resulting by e-aq
      emission in air-free mixture water/ethanol 40/60, as long as they are in "status
      nascendi", can be regenerated by electron transfer from a potent electron donor,
      e.g., vitamin C. The hormone regeneration (%) strongly depends, after all, on
      specific hormone molecular structure, concentration, temperature, etc. Because of
      the large heterogenic molecular structures, the substrates dissolved in the
      solvent mixture form "associates" (unstable complexes) in concentrations >109
      mol/L hormone. The hormones eject, but they also consume e-aq with a rather high
      reaction rate constant (k~109 up to 2*1010 L/mol.s), therefore, they act as
      "electron mediators". It was also observed that the hormones by dissolution in
      aerated solvent mixture are sensitive towards oxygen. For an explanation of the
      results, probable reaction mechanisms are presented. The described method offers
      a new pathway and possibilities for application in medicine. 

PMID- 25961269
TI  - Hormones and the brain.

PMID- 25961270
TI  - Corticosteroid receptor signalling modes and stress adaptation in the brain.
AB  - Adrenal glucocorticoid hormones modulate neuronal activity to support an adaptive
      response to stress. They modulate brain circuitry mediating physiological
      responses, emotion and cognitive processing. Chronically elevated glucocorticoid
      exposure is however linked to the development of mental disease. Glucocorticoid
      effects depend on mineralo- and glucocorticoid receptors, which are powerful
      transcription factors, but also can act via a diversity of non-genomic
      mechanisms. Here, I review generic factors that determine neuronal glucocorticoid
      sensitivity, in relation to brain function. First, pre-receptor mechanisms
      determine ligand availability. Second, there may be considerable variation in the
      receptor splice- and translation variants. Third, other transcription factors and
      many transcriptional coregulators interact with steroid receptors, determining
      nature and magnitude of steroid responses, in part through epigenetic regulation
      of DNA accessibility. Which factors underlie adaptive and pathogenic effects of
      stress hormones is largely unknown. Genome-wide identification of the receptor
      DNA interactions in specific behavioural and physiological contexts provides a
      way of assessing the complete genomic range of glucocorticoid modes of action.
      Novel ligands that induce selective activation of particular receptor signalling
      modes will aid our understanding of receptor signalling and may allow selective
      targeting of glucocorticoid effects in emotional or cognitive domains, in
      research and, hopefully, in clinical settings. 

PMID- 25961271
TI  - Regulation of the hypothalamic-pituitary-adrenal axis by neuropeptides.
AB  - The major endocrine response to stress occurs via activation of the hypothalamic
      pituitary-adrenal (HPA) axis, leading ultimately to increases in circulating
      glucocorticoids, which are essential for the metabolic adaptation to stress. The
      major players in the HPA axis are the hypothalamic neuropeptide, corticotropin
      releasing hormone (CRH), the pituitary hormone adrenocorticotropic hormone, and
      the negative feedback effects of adrenal glucocorticoids. In addition, a number
      of other neuropeptides, including vasopressin (VP), angiotensin II, oxytocin,
      pituitary adenylate cyclase activating peptide, orexin and cholecystokinin, and
      nesfatin can affect HPA axis activity by influencing the expression and secretion
      of CRH, and also by modulating pituitary corticotroph function or adrenal
      steroidogenesis. Of these peptides, VP co-secreted with CRH from axonal terminals
      in the external zone of the median eminence plays a prominent role by
      potentiating the stimulatory effect of CRH and by increasing the number of
      pituitary corticotrophs during chronic challenge. Although the precise role and
      significance of many of these neuropeptides in regulating HPA axis activity
      requires further investigation, it is likely that they are part of a
      multifactorial system mediating the fine tuning of HPA axis activity during
      adaptation to a variety of physiological and stressful conditions. 

PMID- 25961272
TI  - Effect of growth hormone and melatonin on the brain: from molecular mechanisms to
      structural changes.
AB  - Aging of the brain causes important reductions in quality of life and has wide
      socio-economic consequences. An increase in oxidative stress, and the associated
      inflammation and apoptosis, could be responsible for the pathogenesis of aging
      associated brain lesions. Melatonin has neuroprotective effects, by limiting the
      negative effects of oxygen and nitrogen free radicals. Growth hormone (GH) might
      exert additional neuro-protective and or neurogenic effects on the brain. The
      molecular mechanisms of the protective effects of GH and melatonin on the aging
      brain have been investigated in young and old Wistar rats. A reduction in the
      total number of neurons in the hilus of the dentate gyrus was evident at 24
      months of age and was associated with a significant increase in inflammation
      markers as well as in pro-apoptotic parameters, confirming the role of apoptosis
      in its reduction. Melatonin treatment was able to enhance neurogenesis in old
      rats without modification of the total number of neurons, whereas GH treatment
      increased the total number of neurons without enhancing neurogenesis. Both GH and
      melatonin were able to reduce inflammation and apoptosis in the hippocampus. In
      conclusion, neuroprotective effects demonstrated by GH and melatonin in the
      hippocampus were exerted by decreasing inflammation and apoptosis. 

PMID- 25961273
TI  - Leptin and the brain.
AB  - Leptin, which comes from the Greek root leptos meaning thin, has been the focus
      of intense investigation since its discovery in 1994. This hormone belongs to the
      cytokine family and is produced by adipocytes and circulates in proportion to fat
      mass, thus serving as a satiety signal and informing central metabolic control
      centers as to the status of peripheral energy stores. However, it participates in
      numerous other functions both peripherally and centrally, as indicated by the
      wide distribution of its various receptor isoforms. Leptin is involved in brain
      development, most notably in development of hypothalamic centers that control
      metabolism, but also in other brain areas. It acts as a nutritional cue to
      indicate adequacy of energy stores for pubertal development and reproductive
      capacity. The effects of this hormone on behavior and cognition are less well
      studied, but it clearly is involved in specific aspects of these physiological
      phenomena. As obesity is a major health problem in many areas of the world, the
      search for pharmacological treatments to decrease appetite and increase energy
      expenditure is intense. Understanding the mechanisms of actions of all
      physiological effects of this hormone is of great interest in the pursuit of such
      treatment. 

PMID- 25961274
TI  - Regulation of synaptic plasticity by hippocampus synthesized estradiol.
AB  - Estradiol is synthesized from cholesterol in hippocampal neurons of adult rats by
      cytochrome P450 and hydroxysteroid dehydrogenase enzymes. These enzymes are
      expressed in the glutamatergic neurons of the hippocampus. Surprisingly, the
      concentration of estradiol and androgen in the hippocampus is significantly
      higher than that in circulation. Locally synthesized estradiol rapidly and
      potently modulates synaptic plasticity within the hippocampus. E2 rapidly
      potentiates long-term depression and induces spinogenesis through synaptic
      estrogen receptors and kinases. The rapid effects of estradiol are followed by
      slow genomic effects mediated by both estrogen receptors located at the synapse
      and nucleus, modulating long-term potentiation and promoting the formation of new
      functional synaptic contacts. Age-related changes in hippocampally derived
      estradiol synthesis and distribution of estrogen receptors may alter synaptic
      plasticity, and could potentially contribute to age-related cognitive decline.
      Understanding factors which regulate hippocampal estradiol synthesis could lead
      to the identification of alternatives to conventional hormone therapy to protect
      against age-related cognitive decline. 

PMID- 25961275
TI  - Sex differences in the injured brain.
AB  - Observations obtained in human and in experimental models clearly demonstrate sex
      differences in degenerative events occurring in the central nervous system. The
      present review focuses on potential factors that may contribute to these sex
      dimorphic features; in particular, morphological organization of the central
      nervous system and functional influence by neuroactive steroids, genes, and
      immune system are considered. 

PMID- 25961276
TI  - Experimental and clinical evidence for the protective role of progesterone in
      motoneuron degeneration and neuroinflammation.
AB  - Far beyond its role in reproduction, progesterone exerts neuro-protective,
      promyelinating, and anti-inflammatory effects in the nervous system. These
      effects are amplified under pathological conditions, implying that changes of the
      local environment sensitize nervous tissues to steroid therapy. The present
      survey covers our results of progesterone neuroprotection in a motoneuron
      neurodegeneration model and a neuroinflammation model. In the degenerating spinal
      cord of the Wobbler mouse, progesterone reverses the impaired expression of
      neurotrophins, increases enzymes of neurotransmission and metabolism, prevents
      oxidative damage of motoneurons and their vacuolar degeneration (paraptosis), and
      attenuates the development of mitochondrial abnormalities. After long-term
      treatment, progesterone also increases muscle strength and the survival of
      Wobbler mice. Subsequently, this review describes the effects of progesterone in
      mice with induced experimental autoimmune encephalomyelitis (EAE), a commonly
      used model of multiple sclerosis. In EAE mice, progesterone attenuates the
      clinical severity, decreases demyelination and neuronal dysfunction, increases
      axonal counts, reduces the formation of amyloid precursor protein profiles, and
      decreases the aberrant expression of growth-associated proteins. These actions of
      progesterone may be due to multiple mechanisms, considering that classic nuclear
      receptors, extranuclear receptors, and membrane receptors are all expressed in
      the spinal cord. Although many aspects of progesterone action in humans remain
      unsolved, data provided by experimental models makes getting to this objective
      closer than previously expected. 

PMID- 25961277
TI  - Adaptive evolution of Hoxc13 genes in the origin and diversification of the
      vertebrate integument.
AB  - The problem of origination and diversification of integument derivatives in
      vertebrates is still a challenge. The homeobox (Hox) genes Hoxc13 control
      integument formation in vertebrate. Hoxc13 show strong expression in the
      integument development, are highly conserved across vertebrates, and show
      mutations that are associated with skin and appendages. To test whether the
      evolution of the integument is associated with positive selection or relaxation
      of Hoxc13, we obtained these genes in a wide range of vertebrates. In Hoxc13, we
      found evidence of diversifying selection after speciation during the origin of
      vertebrates. In addition, we found the glycine-rich regions in Hoxc13 protein in
      mammals, but not among non-mammalian taxa. Our results strongly implicate that
      Hoxc13 genes could have played an important role in the evolution of integument
      structure.

PMID- 25961279
TI  - Implementation of a targeted screening program to detect airflow obstruction
      suggestive of chronic obstructive pulmonary disease within a presurgical
      screening clinic.
AB  - BACKGROUND: Targeted spirometry screening for chronic obstructive pulmonary
      disease (COPD) has been studied in primary care and community settings.
      Limitations regarding availability and quality of testing remain. A targeted
      spirometry screening program was implemented within a presurgical screening (PSS)
      clinic to detect undiagnosed airways disease and identify patients with
      COPD/asthma in need of treatment optimization. OBJECTIVE: The present quality
      assurance study evaluated airflow obstruction detection rates and examined
      characteristics of patients identified through the targeted screening program.
      METHODS: The targeted spirometry screening program was implemented within the PSS
      clinic of a tertiary care university hospital. Current or ex-smokers with
      respiratory symptoms and patients with a history of COPD or asthma underwent
      prebronchodilator spirometry. History of airways disease and smoking status were
      obtained during the PSS assessment and confirmed through chart reviews. RESULTS:
      After exclusions, the study sample included 449 current or ex-smokers. Abnormal
      spirometry results were found in 184 (41%) patients: 73 (16%) had mild, 93 (21%)
      had moderate and 18 (4%) had severe or very severe airflow obstruction. One
      hundred eighteen (26%) new cases of airflow obstruction suggestive of COPD were
      detected. One-half of these new cases had moderate or severe airflow obstruction.
      Only 34% of patients with abnormal spirometry results had reported a previous
      diagnosis of COPD. More than one-half of patients with abnormal spirometry
      results were current smokers. CONCLUSIONS: Undiagnosed airflow obstruction was
      detected in a significant number of smokers and ex-smokers through a targeted
      screening program within a PSS clinic. These patients can be referred for early
      intervention and secondary preventive strategies.

PMID- 25961281
TI  - Implied actions between paired objects lead to affordance selection by
      inhibition.
AB  - Evidence from experiments with single objects indicates that perceiving objects
      leads to automatic extraction of affordances. Here we examined the influence of
      implied between-object actions on affordance processing. Images of task
      irrelevant object pairs (e.g., a spoon and a bowl) were followed by imperative
      central targets. Participants made speeded left/right responses to targets, and
      the responses randomly aligned with the affordance of one of the objects. The
      orientation of one object was manipulated across trials, leaving the colocation
      between objects correct or incorrect for potential interaction. Four experiments
      demonstrated that positioning the objects correctly for between-object actions
      led to a prioritization of the object active in the action (e.g., the spoon) over
      the passive (e.g., the bowl) object. Moreover, there was an inhibitory effect on
      responses to the passive object: responses congruent with the passive object were
      slower when pairs of objects were shown as if in interaction, compared with when
      they were not. The effects did not change in the single-hand response task but
      disappeared when the passive objects were absent-though an affordance should
      still have been presented by the active object. These results present evidence
      for affordance selection in action-related object pairs, and suggest inhibition
      of the action afforded by the passive objects under conditions of affordance
      competition.

PMID- 25961280
TI  - The effects of outdoor air pollution on the respiratory health of Canadian
      children: A systematic review of epidemiological studies.
AB  - BACKGROUND: Outdoor air pollution is a global problem with serious effects on
      human health, and children are considered to be highly susceptible to the effects
      of air pollution. OBJECTIVE: To conduct a comprehensive and updated systematic
      review of the literature reporting the effects of outdoor air pollution on the
      respiratory health of children in Canada. METHODS: Searches of four electronic
      databases between January 2004 and November 2014 were conducted to identify
      epidemiological studies evaluating the effect of exposure to outdoor air
      pollutants on respiratory symptoms, lung function measurements and the use of
      health services due to respiratory conditions in Canadian children. The selection
      process and quality assessment, using the Newcastle-Ottawa Scale, were conducted
      independently by two reviewers. RESULTS: Twenty-seven studies that were
      heterogeneous with regard to study design, population, respiratory outcome and
      air pollution exposure were identified. Overall, the included studies reported
      adverse effects of outdoor air pollution at concentrations that were below
      Canadian and United States standards. Heterogeneous effects of air pollutants
      were reported according to city, sex, socioeconomic status and seasonality. The
      present review also describes trends in research related to the effect of air
      pollution on Canadian children over the past 25 years. CONCLUSION: The present
      study reconfirms the adverse effects of outdoor air pollution on the respiratory
      health of children in Canada. It will help researchers, clinicians and
      environmental health authorities identify the available evidence of the adverse
      effect of outdoor air pollution, research gaps and the limitations for further
      research.

PMID- 25961282
TI  - Chemotherapeutic Drugs Interfere with Gene Delivery Mediated by Chitosan-Graft
      Poly(ethylenimine).
AB  - Combined chemo-gene therapy is one of the treatment modalities that have
      attracted extensive research interests; however, there is little information
      regarding the influence of drug application on gene transfer. This study bridges
      this gap by examining how chemotherapeutic drugs (teniposide, cis
      diamminedichloroplatinum(II) and temozolomide) interfere with polyplex formation
      and transfection of chitosan-graft-poly(ethylenimine). Our results indicate that
      the degree of drug interference varies with the mechanism of drug action, with
      the transgene expression being severely suppressed when the plasmid is co
      delivered with cis-diamminedichloroplatinum(II) or teniposide but not
      temozolomide. In addition, the interference with transfection by drugs varies
      with different gene/drug co-formulations. This is the first study to evidence
      that, though combined chemo-gene therapy has therapeutic potential, some
      chemotherapeutic drugs may reduce the treatment efficiency of gene therapy. 

PMID- 25961284
TI  - Acute glucagon induces postprandial peripheral insulin resistance.
AB  - Glucagon levels are often moderately elevated in diabetes. It is known that
      glucagon leads to a decrease in hepatic glutathione (GSH) synthesis that in turn
      is associated with decreased postprandial insulin sensitivity. Given that cAMP
      pathway controls GSH levels we tested whether insulin sensitivity decreases after
      intraportal (ipv) administration of a cAMP analog (DBcAMP), and investigated
      whether glucagon promotes insulin resistance through decreasing hepatic GSH
      levels.Insulin sensitivity was determined in fed male Sprague-Dawley rats using a
      modified euglycemic hyperinsulinemic clamp in the postprandial state upon ipv
      administration of DBcAMP as well as glucagon infusion. Glucagon effects on
      insulin sensitivity was assessed in the presence or absence of postprandial
      insulin sensitivity inhibition by administration of L-NMMA. Hepatic GSH and NO
      content and plasma levels of NO were measured after acute ipv glucagon infusion.
      Insulin sensitivity was assessed in the fed state and after ipv glucagon infusion
      in the presence of GSH-E. We founf that DBcAMP and glucagon produce a decrease of
      insulin sensitivity, in a dose-dependent manner. Glucagon-induced decrease of
      postprandial insulin sensitivity correlated with decreased hepatic GSH content
      and was restored by administration of GSH-E. Furthermore, inhibition of
      postprandial decrease of insulin sensitivity L-NMMA was not overcome by glucagon,
      but glucagon did not affect hepatic and plasma levels of NO. These results show
      that glucagon decreases postprandial insulin sensitivity through reducing hepatic
      GSH levels, an effect that is mimicked by increasing cAMP hepatic levels and
      requires physiological NO levels. These observations support the hypothesis that
      glucagon acts via adenylate cyclase to decrease hepatic GSH levels and induce
      insulin resistance. We suggest that the glucagon-cAMP-GSH axis is a potential
      therapeutic target to address insulin resistance in pathological conditions. 

PMID- 25961283
TI  - A Phase I Double Blind, Placebo-Controlled, Randomized Study of the Safety and
      Immunogenicity of an Adjuvanted HIV-1 Gag-Pol-Nef Fusion Protein and Adenovirus
      35 Gag-RT-Int-Nef Vaccine in Healthy HIV-Uninfected African Adults.
AB  - BACKGROUND: Sequential prime-boost or co-administration of HIV vaccine candidates
      based on an adjuvanted clade B p24, RT, Nef, p17 fusion protein (F4/AS01) plus a
      non-replicating adenovirus 35 expressing clade A Gag, RT, Int and Nef (Ad35-GRIN)
      may lead to a unique immune profile, inducing both strong T-cell and antibody
      responses. METHODS: In a phase 1, double-blind, placebo-controlled trial, 146
      healthy adult volunteers were randomized to one of four regimens: heterologous
      prime-boost with two doses of F4/AS01E or F4/AS01B followed by Ad35-GRIN; Ad35
      GRIN followed by two doses of F4/AS01B; or three co-administrations of Ad35-GRIN
      and F4/AS01B. T cell and antibody responses were measured. RESULTS: The vaccines
      were generally well-tolerated, and did not cause serious adverse events. The
      response rate, by IFN-gamma ELISPOT, was greater when Ad35-GRIN was the priming
      vaccine and in the co-administration groups. F4/AS01 induced CD4+ T-cells
      expressing primarily CD40L and IL2 +/- TNF-alpha, while Ad35-GRIN induced
      predominantly CD8+ T-cells expressing IFN-gamma +/- IL2 or TNF-alpha. Viral
      inhibition was induced after Ad35-GRIN vaccination, regardless of the regimen.
      Strong F4-specific antibody responses were induced. Immune responses persisted at
      least a year after the last vaccination. The complementary response profiles,
      characteristic of each vaccine, were both expressed after co-administration.
      CONCLUSION: Co-administration of an adjuvanted protein and an adenovirus vector
      showed an acceptable safety and reactogenicity profile and resulted in strong,
      multifunctional and complementary HIV-specific immune responses. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01264445.

PMID- 25961285
TI  - Numerical Modeling of Intraventricular Flow during Diastole after Implantation of
      BMHV.
AB  - This work presents a numerical simulation of intraventricular flow after the
      implantation of a bileaflet mechanical heart valve at the mitral position. The
      left ventricle was simplified conceptually as a truncated prolate spheroid and
      its motion was prescribed based on that of a healthy subject. The rigid leaflet
      rotation was driven by the transmitral flow and hence the leaflet dynamics were
      solved using fluid-structure interaction approach. The simulation results showed
      that the bileaflet mechanical heart valve at the mitral position behaved
      similarly to that at the aortic position. Sudden area expansion near the aortic
      root initiated a clockwise anterior vortex, and the continuous injection of flow
      through the orifice resulted in further growth of the anterior vortex during
      diastole, which dominated the intraventricular flow. This flow feature is
      beneficial to preserving the flow momentum and redirecting the blood flow towards
      the aortic valve. To the best of our knowledge, this is the first attempt to
      numerically model intraventricular flow with the mechanical heart valve
      incorporated at the mitral position using a fluid-structure interaction approach.
      This study facilitates future patient-specific studies. 

PMID- 25961286
TI  - A novel candidate region for genetic adaptation to high altitude in Andean
      populations.
AB  - Humans living at high altitude (>= 2,500 meters above sea level) have acquired
      unique abilities to survive the associated extreme environmental conditions,
      including hypoxia, cold temperature, limited food availability and high levels of
      free radicals and oxidants. Long-term inhabitants of the most elevated regions of
      the world have undergone extensive physiological and/or genetic changes,
      particularly in the regulation of respiration and circulation, when compared to
      lowland populations. Genome scans have identified candidate genes involved in
      altitude adaption in the Tibetan Plateau and the Ethiopian highlands, in contrast
      to populations from the Andes, which have not been as intensively investigated.
      In the present study, we focused on three indigenous populations from Bolivia:
      two groups of Andean natives, Aymara and Quechua, and the low-altitude control
      group of Guarani from the Gran Chaco lowlands. Using pooled samples, we
      identified a number of SNPs exhibiting large allele frequency differences over
      900,000 genotyped SNPs. A region in chromosome 10 (within the cytogenetic bands
      q22.3 and q23.1) was significantly differentiated between highland and lowland
      groups. We resequenced ~1.5 Mb surrounding the candidate region and identified
      strong signals of positive selection in the highland populations. A composite of
      multiple signals like test localized the signal to FAM213A and a related
      enhancer; the product of this gene acts as an antioxidant to lower oxidative
      stress and may help to maintain bone mass. The results suggest that positive
      selection on the enhancer might increase the expression of this antioxidant, and
      thereby prevent oxidative damage. In addition, the most significant signal in a
      relative extended haplotype homozygosity analysis was localized to the SFTPD
      gene, which encodes a surfactant pulmonary-associated protein involved in normal
      respiration and innate host defense. Our study thus identifies two novel
      candidate genes and associated pathways that may be involved in high-altitude
      adaptation in Andean populations.

PMID- 25961287
TI  - Globular Adiponectin Causes Tolerance to LPS-Induced TNF-alpha Expression via
      Autophagy Induction in RAW 264.7 Macrophages: Involvement of SIRT1/FoxO3A Axis.
AB  - Adiponectin, an adipokine predominantly produced from adipose tissue, exhibited
      potent anti-inflammatory properties. In particular, it inhibits production of pro
      inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), in
      macrophages. Autophagy, an intracellular self-digestion process, has been
      recently shown to regulate inflammatory responses. In the present study, we
      investigated the role of autophagy induction in the suppression of
      Lipopolysaccharide (LPS) -induced TNF-alpha expression by globular adiponectin
      (gAcrp) and its potential mechanisms. Herein, we found that gAcrp treatment
      increased expression of genes related with autophagy, including Atg5 and
      microtubule-associated protein light chain (LC3B), induced autophagosome
      formation and autophagy flux in RAW 264.7 macrophages. Similar results were
      observed in primary macrophages isolated peritoneum of mice. Interestingly,
      inhibition of autophagy by pretreatment with Bafilomycin A1 or knocking down of
      LC3B gene restored suppression of TNF-alpha expression, tumor necrosis factor
      receptor- associated factor 6 (TRAF6) expression and p38MAPK phosphorylation by
      gAcrp, implying a critical role of autophagy induction in the development of
      tolerance to LPS-induced TNF-alpha expression by gAcrp. We also found that
      knocking-down of FoxO3A, a forkhead box O member of transcription factor, blocked
      gAcrp-induced expression of LC3II and Atg5. Moreover, gene silencing of Silent
      information regulator 1 (SIRT1) blocked both gAcrp-induced nuclear translocation
      of FoxO3A and LC3II expression. Finally, pretreatment with ROS inhibitors,
      prevented gAcrp-induced SIRT1 expression and further generated inhibitory effects
      on gAcrp-induced autophagy, indicating a role of ROS production in gAcrp-induced
      SIRT1 expression and subsequent autophagy induction. Taken together, these
      findings indicate that globular adiponectin suppresses LPS-induced TNF-alpha
      expression, at least in part, via autophagy activation. Furthermore, SIRT1-FoxO3A
      axis plays a crucial role in gAcrp-induced autophagy in macrophages. 

PMID- 25961288
TI  - Discovery of an inhibitor of Z-alpha1 antitrypsin polymerization.
AB  - Polymerization of the Z variant alpha-1-antitrypsin (Z-alpha1AT) results in the
      most common and severe form of alpha1AT deficiency (alpha1ATD), a debilitating
      genetic disorder whose clinical manifestations range from asymptomatic to fatal
      liver and/or lung disease. As the altered conformation of Z-alpha1AT and its
      attendant aggregation are responsible for pathogenesis, the polymerization
      process per se has become a major target for the development of therapeutics.
      Based on the ability of Z-alpha1AT to aggregate by recruiting the reactive center
      loop (RCL) of another Z-alpha1AT into its s4A cavity, we developed a high
      throughput screening assay that uses a modified 6-mer peptide mimicking the RCL
      to screen for inhibitors of Z-alpha1AT polymer growth. A subset of compounds from
      the Library of Pharmacologically Active Compounds (LOPAC) with molecular weights
      ranging from 300 to 700 Da, was used to evaluate the assay's capabilities. The
      inhibitor S-(4-nitrobenzyl)-6-thioguanosine was identified as a lead compound and
      its ability to prevent Z-alpha1AT polymerization confirmed by secondary assays.
      To further investigate the binding location of S-(4-nitrobenzyl)-6-thioguanosine,
      an in silico strategy was pursued and the intermediate alpha1AT M* state modeled
      to allow molecular docking simulations and explore various potential binding
      sites. Docking results predict that S-(4-nitrobenzyl)-6-thioguanosine can bind at
      the s4A cavity and at the edge of beta-sheet A. The former binding site would
      directly block RCL insertion whereas the latter site would prevent beta-sheet A
      from expanding between s3A/s5A, and thus indirectly impede RCL insertion.
      Altogether, our investigations have revealed a novel compound that inhibits the
      formation of Z-alpha1AT polymers, as well as in vitro and in silico strategies
      for identifying and characterizing additional blocking molecules of Z-alpha1AT
      polymerization. 

PMID- 25961289
TI  - Morbidity Rate Prediction of Dengue Hemorrhagic Fever (DHF) Using the Support
      Vector Machine and the Aedes aegypti Infection Rate in Similar Climates and
      Geographical Areas.
AB  - BACKGROUND: In the past few decades, several researchers have proposed highly
      accurate prediction models that have typically relied on climate parameters.
      However, climate factors can be unreliable and can lower the effectiveness of
      prediction when they are applied in locations where climate factors do not differ
      significantly. The purpose of this study was to improve a dengue surveillance
      system in areas with similar climate by exploiting the infection rate in the
      Aedes aegypti mosquito and using the support vector machine (SVM) technique for
      forecasting the dengue morbidity rate. METHODS AND FINDINGS: Areas with high
      incidence of dengue outbreaks in central Thailand were studied. The proposed
      framework consisted of the following three major parts: 1) data integration, 2)
      model construction, and 3) model evaluation. We discovered that the Ae. aegypti
      female and larvae mosquito infection rates were significantly positively
      associated with the morbidity rate. Thus, the increasing infection rate of female
      mosquitoes and larvae led to a higher number of dengue cases, and the prediction
      performance increased when those predictors were integrated into a predictive
      model. In this research, we applied the SVM with the radial basis function (RBF)
      kernel to forecast the high morbidity rate and take precautions to prevent the
      development of pervasive dengue epidemics. The experimental results showed that
      the introduced parameters significantly increased the prediction accuracy to
      88.37% when used on the test set data, and these parameters led to the highest
      performance compared to state-of-the-art forecasting models. CONCLUSIONS: The
      infection rates of the Ae. aegypti female mosquitoes and larvae improved the
      morbidity rate forecasting efficiency better than the climate parameters used in
      classical frameworks. We demonstrated that the SVM-R-based model has high
      generalization performance and obtained the highest prediction performance
      compared to classical models as measured by the accuracy, sensitivity,
      specificity, and mean absolute error (MAE).

PMID- 25961291
TI  - Correction: Improving Men's Participation in Preventing Mother-to-Child
      Transmission of HIV as a Maternal, Neonatal, and Child Health Priority in South
      Africa.

PMID- 25961290
TI  - Extraction of pharmacokinetic evidence of drug-drug interactions from the
      literature.
AB  - Drug-drug interaction (DDI) is a major cause of morbidity and mortality and a
      subject of intense scientific interest. Biomedical literature mining can aid DDI
      research by extracting evidence for large numbers of potential interactions from
      published literature and clinical databases. Though DDI is investigated in
      domains ranging in scale from intracellular biochemistry to human populations,
      literature mining has not been used to extract specific types of experimental
      evidence, which are reported differently for distinct experimental goals. We
      focus on pharmacokinetic evidence for DDI, essential for identifying causal
      mechanisms of putative interactions and as input for further pharmacological and
      pharmacoepidemiology investigations. We used manually curated corpora of PubMed
      abstracts and annotated sentences to evaluate the efficacy of literature mining
      on two tasks: first, identifying PubMed abstracts containing pharmacokinetic
      evidence of DDIs; second, extracting sentences containing such evidence from
      abstracts. We implemented a text mining pipeline and evaluated it using several
      linear classifiers and a variety of feature transforms. The most important
      textual features in the abstract and sentence classification tasks were analyzed.
      We also investigated the performance benefits of using features derived from
      PubMed metadata fields, various publicly available named entity recognizers, and
      pharmacokinetic dictionaries. Several classifiers performed very well in
      distinguishing relevant and irrelevant abstracts (reaching F1~0.93, MCC~0.74,
      iAUC~0.99) and sentences (F1~0.76, MCC~0.65, iAUC~0.83). We found that word
      bigram features were important for achieving optimal classifier performance and
      that features derived from Medical Subject Headings (MeSH) terms significantly
      improved abstract classification. We also found that some drug-related named
      entity recognition tools and dictionaries led to slight but significant
      improvements, especially in classification of evidence sentences. Based on our
      thorough analysis of classifiers and feature transforms and the high
      classification performance achieved, we demonstrate that literature mining can
      aid DDI discovery by supporting automatic extraction of specific types of
      experimental evidence. 

PMID- 25961292
TI  - Neutrophil-to-Lymphocyte Ratio Is Associated with Impaired Interferon-Gamma
      Release to Phytohemagglutinin.
AB  - OBJECTIVE: The neutrophil-to-lymphocyte ratio (NLR) has been shown to predict
      adverse outcomes in several pathologic conditions. The majority of indeterminate
      interferon (IFN)-gamma release assays were due to inadequate IFN-gamma response
      to the phytohemagglutinin. We sought to study the value of NLR to predict an
      indeterminate result of QuantiFERON-TB Gold In-Tube (QFT-GIT) performed in
      routine laboratory practice. METHODS: Results from 2,773 QFT-GIT assays were
      analyzed. Data collection included demographic data, the level of IFN-gamma to
      nil, mitogen, and TB antigen of QFT-GIT, total WBC, and a differential count. We
      calculated the absolute neutrophil count, lymphocyte count, and NLR. RESULTS: Of
      the total, 224 (8.1%) indeterminate results were observed. Twelve (1.8%) showed
      indeterminate results in the NLR range from 1.71 to 2.84, but 132 (19.2%) had
      indeterminate results in NLR >= 5.18 (p < 0.0001). The likelihood ratio for
      indeterminate results were 2.70 (95% CI, 2.36-3.08) in NLR >= 5.18 and 1.93 (95%
      CI, 1.64-2.27) in lymphocyte count <= 1050/MUL. NLR and neutrophil count were
      independent predictors for indeterminate QFT-GIT result in multiple regression
      analysis. The IFN-gamma response to PHA was negatively associated with NLR (r = 
      0.33, p < 0.001). CONCLUSION: We showed that the NLR is an independent predictor
      of indeterminate QFT-GIT result. Low frequency of indeterminate results in group
      with normal NLR may imply the importance of a balance between two cellular
      compartments in physiological and pathological conditions.

PMID- 25961293
TI  - Acceptability and use of portable drinking water and hand washing stations in
      health care facilities and their impact on patient hygiene practices, Western
      kenya.
AB  - Many health care facilities (HCF) in developing countries lack access to reliable
      hand washing stations and safe drinking water. To address this problem, we
      installed portable, low-cost hand washing stations (HWS) and drinking water
      stations (DWS), and trained healthcare workers (HCW) on hand hygiene, safe
      drinking water, and patient education techniques at 200 rural HCFs lacking a
      reliable water supply in western Kenya. We performed a survey at baseline and a
      follow-up evaluation at 15 months to assess the impact of the intervention at a
      random sample of 40 HCFs and 391 households nearest to these HCFs. From baseline
      to follow-up, there was a statistically significant increase in the percentage of
      dispensaries with access to HWSs with soap (42% vs. 77%, p<0.01) and access to
      safe drinking water (6% vs. 55%, p<0.01). Female heads of household in the HCF
      catchment area exhibited statistically significant increases from baseline to
      follow-up in the ability to state target times for hand washing (10% vs. 35%,
      p<0.01), perform all four hand washing steps correctly (32% vs. 43%, p = 0.01),
      and report treatment of stored drinking water using any method (73% vs. 92%,
      p<0.01); the percentage of households with detectable free residual chlorine in
      stored drinking water did not change (6%, vs. 8%, p = 0.14). The installation of
      low-cost, low-maintenance, locally-available, portable hand washing and drinking
      water stations in rural HCFs without access to 24-hour piped water helped assure
      that health workers had a place to wash their hands and provide safe drinking
      water. This HCF intervention may have also contributed to the improvement of hand
      hygiene and reported safe drinking water behaviors among households nearest to
      HCFs. 

PMID- 25961294
TI  - Dead or Alive? Factors Affecting the Survival of Victims during Attacks by
      Saltwater Crocodiles (Crocodylus porosus) in Australia.
AB  - Conflicts between humans and crocodilians are a widespread conservation challenge
      and the number of crocodile attacks is increasing worldwide. We identified the
      factors that most effectively decide whether a victim is injured or killed in a
      crocodile attack by fitting generalized linear models to a 42-year dataset of 87
      attacks (27 fatal and 60 non-fatal) by saltwater crocodiles (Crocodylus porosus)
      in Australia. The models showed that the most influential factors were the
      difference in body mass between crocodile and victim, and the position of victim
      in relation to the water at the time of an attack. In-water position (for diving,
      swimming, and wading) had a higher risk than on-water (boating) or on-land
      (fishing, and hunting near the water's edge) positions. In the in-water position
      a 75 kg person would have a relatively high probability of survival (0.81) if
      attacked by a 300 cm crocodile, but the probability becomes much lower (0.17)
      with a 400 cm crocodile. If attacked by a crocodile larger than 450 cm, the
      survival probability would be extremely low (<0.05) regardless of the victim's
      size. These results indicate that the main cause of death during a crocodile
      attack is drowning and larger crocodiles can drag a victim more easily into
      deeper water. A higher risk associated with a larger crocodile in relation to
      victim's size is highlighted by children's vulnerability to fatal attacks. Since
      the first recently recorded fatal attack involving a child in 2006, six out of
      nine fatal attacks (66.7%) involved children, and the average body size of
      crocodiles responsible for these fatal attacks was considerably smaller (384 cm,
      223 kg) than that of crocodiles that killed adults (450 cm, 324 kg) during the
      same period (2006-2014). These results suggest that culling programs targeting
      larger crocodiles may not be an effective management option to improve safety for
      children. 

PMID- 25961295
TI  - A newton cooperative genetic algorithm method for in silico optimization of
      metabolic pathway production.
AB  - This paper presents an in silico optimization method of metabolic pathway
      production. The metabolic pathway can be represented by a mathematical model
      known as the generalized mass action model, which leads to a complex nonlinear
      equations system. The optimization process becomes difficult when steady state
      and the constraints of the components in the metabolic pathway are involved. To
      deal with this situation, this paper presents an in silico optimization method,
      namely the Newton Cooperative Genetic Algorithm (NCGA). The NCGA used Newton
      method in dealing with the metabolic pathway, and then integrated genetic
      algorithm and cooperative co-evolutionary algorithm. The proposed method was
      experimentally applied on the benchmark metabolic pathways, and the results
      showed that the NCGA achieved better results compared to the existing methods. 

PMID- 25961296
TI  - Exome Sequencing Identifies a Mutation in EYA4 as a Novel Cause of Autosomal
      Dominant Non-Syndromic Hearing Loss.
AB  - Autosomal dominant non-syndromic hearing loss is highly heterogeneous, and eyes
      absent 4 (EYA4) is a disease-causing gene. Most EYA4 mutations founded in the Eya
      homologous region, however, no deafness causative missense mutation in variable
      region of EYA4 have previously been found. In this study, we identified a
      pathogenic missense mutation located in the variable region of the EYA4 gene for
      the first time in a four-generation Chinese family with 57 members. Whole-exome
      sequencing (WES) was performed on samples from one unaffected and two affected
      individuals to systematically search for deafness susceptibility genes, and the
      candidate mutations and the co-segregation of the phenotype were verified by
      polymerase chain reaction amplification and by Sanger sequencing in all of the
      family members. Then, we identified a novel EYA4 mutation in exon 8, c.511G>C;
      p.G171R, which segregated with postlingual and progressive autosomal dominant
      sensorineural hearing loss (SNHL). This report is the first to describe a
      missense mutation in the variable region domain of the EYA4 gene, which is not
      highly conserved in many species, indicating that the potential unconserved role
      of 171G>R in human EYA4 function is extremely important. 

PMID- 25961297
TI  - BrainSignals Revisited: Simplifying a Computational Model of Cerebral Physiology.
AB  - Multimodal monitoring of brain state is important both for the investigation of
      healthy cerebral physiology and to inform clinical decision making in conditions
      of injury and disease. Near-infrared spectroscopy is an instrument modality that
      allows non-invasive measurement of several physiological variables of clinical
      interest, notably haemoglobin oxygenation and the redox state of the metabolic
      enzyme cytochrome c oxidase. Interpreting such measurements requires the
      integration of multiple signals from different sources to try to understand the
      physiological states giving rise to them. We have previously published several
      computational models to assist with such interpretation. Like many models in the
      realm of Systems Biology, these are complex and dependent on many parameters that
      can be difficult or impossible to measure precisely. Taking one such model,
      BrainSignals, as a starting point, we have developed several variant models in
      which specific regions of complexity are substituted with much simpler linear
      approximations. We demonstrate that model behaviour can be maintained whilst
      achieving a significant reduction in complexity, provided that the linearity
      assumptions hold. The simplified models have been tested for applicability with
      simulated data and experimental data from healthy adults undergoing a hypercapnia
      challenge, but relevance to different physiological and pathophysiological
      conditions will require specific testing. In conditions where the simplified
      models are applicable, their greater efficiency has potential to allow their use
      at the bedside to help interpret clinical data in near real-time. 

PMID- 25961298
TI  - Coordinated Expression of FLOWERING LOCUS T and DORMANCY ASSOCIATED MADS-BOX-Like
      Genes in Leafy Spurge.
AB  - Leafy spurge (Euphorbia esula L.) is a noxious perennial weed that produces
      underground adventitious buds, which are crucial for generating new vegetative
      shoots following periods of freezing temperatures or exposure to various control
      measures. It is also capable of flowering and producing seeds, but requires
      vernalization in some cases. DORMANCY ASSOCIATED MADS-BOX (DAM) genes have been
      proposed to play a direct role in the transition to winter-induced dormancy and
      maintenance through regulation of the FLOWERING LOCUS T (FT) gene, which also is
      likely involved in the vernalization process. To explore the regulation of FT and
      DAM during dormancy transitions in leafy spurge, the transcript accumulation of
      two previously cloned DAM splice variants and two different previously cloned FT
      genes was characterized. Under long-photoperiods (16 h light), both DAM and FT
      transcripts accumulate in a diurnal manner. Tissue specific expression patterns
      indicated the tissues with high DAM expression had low FT expression and vice
      versa. DAM expression is detected in leaves, stems, shoot tips, and crown buds.
      FT transcripts were detected mainly in leaves and flowers. Under dormancy
      inducing conditions, DAM and FT genes had an inverse expression pattern.
      Additionally, chromatin immunoprecipitation assays were performed using DAM-like
      protein specific antibodies to demonstrate that DAM or related proteins likely
      bind to cryptic and/or conserved CArG boxes in the promoter regions of FT genes
      isolated from endodormant crown buds. These results are consistent with the
      hypothesis that DAM proteins play a crucial role in leafy spurge dormancy
      transition and maintenance, potentially by negatively regulating the expression
      of FT. 

PMID- 25961299
TI  - Temporal Co-Variation between Eye Lens Accommodation and Trapezius Muscle
      Activity during a Dynamic Near-Far Visual Task.
AB  - Near work is associated with increased activity in the neck and shoulder muscles,
      but the underlying mechanism is still unknown. This study was designed to
      determine whether a dynamic change in focus, alternating between a nearby and a
      more distant visual target, produces a direct parallel change in trapezius muscle
      activity. Fourteen healthy controls and 12 patients with a history of visual and
      neck/shoulder symptoms performed a Near-Far visual task under three different
      viewing conditions; one neutral condition with no trial lenses, one condition
      with negative trial lenses to create increased accommodation, and one condition
      with positive trial lenses to create decreased accommodation. Eye lens
      accommodation and trapezius muscle activity were continuously recorded. The
      trapezius muscle activity was significantly higher during Near than during Far
      focusing periods for both groups within the neutral viewing condition, and there
      was a significant co-variation in time between accommodation and trapezius muscle
      activity within the neutral and positive viewing conditions for the control
      group. In conclusion, these results reveal a connection between Near focusing and
      increased muscle activity during dynamic changes in focus between a nearby and a
      far target. A direct link, from the accommodation/vergence system to the
      trapezius muscles cannot be ruled out, but the connection may also be explained
      by an increased need for eye-neck (head) stabilization when focusing on a nearby
      target as compared to a more distant target. 

PMID- 25961301
TI  - Correction: Dual logic and cerebral coordinates for reciprocal interaction in eye
      contact.

PMID- 25961300
TI  - Patterns in species persistence and biomass production in soil microcosms
      recovering from a disturbance reject a neutral hypothesis for bacterial community
      assembly.
AB  - The neutral theory of biodiversity has emerged as a major null hypothesis in
      community ecology. The neutral theory may sufficiently well explain the
      structuring of microbial communities as the extremely high microbial diversity
      has led to an expectation of high ecological equivalence among species. To
      address this possibility, we worked with microcosms of two soils; the microcosms
      were either exposed, or not, to a dilution disturbance which reduces community
      sizes and removes some very rare species. After incubation for recovery, changes
      in bacterial species composition in microcosms compared with the source soils
      were assessed by pyrosequencing of bacterial 16S rRNA genes. Our assays could
      detect species with a proportional abundance >= 0.0001 in each community, and
      changes in the abundances of these species should have occurred during the
      recovery growth, but not be caused by the disturbance per se. The undisturbed
      microcosms showed slight changes in bacterial species diversity and composition,
      with a small number of initially low-abundance species going extinct. In
      microcosms recovering from the disturbance, however, species diversity decreased
      dramatically (by > 50%); and in most cases there was not a positive relationship
      between species initial abundance and their chance of persistence. Furthermore, a
      positive relationship between species richness and community biomass was observed
      in microcosms of one soil, but not in those of the other soil. The results are
      not consistent with a neutral hypothesis that predicts a positive abundance
      persistence relationship and a null effect of diversity on ecosystem functioning.
      Adaptation mechanisms, in particular those associated with species interactions
      including facilitation and predation, may provide better explanations. 

PMID- 25961302
TI  - Narcissism as a moderator of satisfaction with body image in young women with
      extreme underweight and obesity.
AB  - OBJECTIVE: Body weight and age constitute main determinants of body image in
      women. We analyzed the role of narcissism as a moderator of body image in young
      women representing various extremes of body weight. METHODS: The study included
      325 women between 18 and 35 years, qualified into three BMI categories: obese
      women (BMI > 30.0, n = 72), severely underweight women who did not satisfy the
      remaining criteria of anorexia (BMI < 17.5, n = 85), and women with normal body
      weight (21.7 < "ideal BMI" > 22.7, n = 168). Satisfaction with body image was
      determined with Multidimensional Body-Self Relations Questionnaire and Body
      Esteem Scale, while narcissism was measured with Narcissistic Personality
      Inventory. PRINCIPAL FINDINGS: We revealed that narcissism has significant impact
      on the body image of women who are extremely underweight or obese. Vanity and
      Leadership were narcissism dimensions which played significant role in slim
      women, as compared to Vanity and Self-Sufficiency in obese women. CONCLUSION: The
      role of narcissism as a modulator of self-satisfaction with one's body varies
      depending on BMI level: extremely underweight women and obese individuals
      constitute groups in which narcissism has the strongest impact on the self
      satisfaction with body.

PMID- 25961303
TI  - Lumican is overexpressed in lung adenocarcinoma pleural effusions.
AB  - Adenocarcinoma (AdC) is the most common lung cancer subtype and is often
      associated with pleural effusion (PE). Its poor prognosis is attributable to
      diagnostic delay and lack of effective treatments and there is a pressing need in
      discovering new biomarkers for early diagnosis or targeted therapies. To date,
      little is known about lung AdC proteome. We investigated protein expression of
      lung AdC in PE using the isobaric Tags for Relative and Absolute Quantification
      (iTRAQ) approach to identify possible novel diagnostic/prognostic biomarkers.
      This provided the identification of 109 of lung AdC-related proteins. We further
      analyzed lumican, one of the overexpressed proteins, in 88 resected lung AdCs and
      in 23 malignant PE cell-blocks (13 lung AdCs and 10 non-lung cancers) using
      immunohistochemistry. In AdC surgical samples, lumican expression was low in
      cancer cells, whereas it was strong and diffuse in the stroma surrounding the
      tumor. However, lumican expression was not associated with tumor grade, stage,
      and vascular/pleural invasion. None of the lung cancer cell-blocks showed lumican
      immunoreaction, whereas those of all the other tumors were strongly positive.
      Finally, immunoblotting analysis showed lumican expression in both cell lysate
      and conditioned medium of a fibroblast culture but not in those of A549 lung
      cancer cell line. PE is a valid source of information for proteomic analysis
      without many of the restrictions of plasma. The high lumican levels
      characterizing AdC PEs are probably due to its release by the fibroblasts
      surrounding the tumor. Despite the role of lumican in lung AdC is still elusive,
      it could be of diagnostic value. 

PMID- 25961304
TI  - Study and characterization of an ancient European flint white maize rich in
      anthocyanins: Millo Corvo from Galicia.
AB  - In the second half of the last century, the American dent hybrids began to be
      widely grown, leading to the disappearance or marginalization of the less
      productive traditional varieties. Nowadays the characterization of traditional
      landraces can help breeders to discover precious alleles that could be useful for
      modern genetic improvement and allow a correct conservation of these open
      pollinated varieties (opvs). In this work we characterized the ancient coloured
      cultivar "Millo Corvo" typical of the Spanish region of Galicia. We showed that
      this cultivar accumulates high amounts of anthocyanins (83.4 mg/100g flour), and
      by TLC (Thin Layer Chromatography) and HPLC (High Pressure Liquid Chromatography)
      analysis, we demonstrated that they mainly consisted of cyanidin. Mapping and
      sequencing data demonstrate that anthocyanin pigmentation is due to the presence
      of the red color1 gene(r1), a transcription factor driving the accumulation of
      this pigment in the aleurone layer. Further chemical analysis showed that the
      kernels are lacking in carotenoids, as confirmed by genetic study. Finally a DPPH
      (2,2-diphenyl-1-picrylhydrazyl) radical scavenging ability test showed that Millo
      Corvo, even though lacking carotenoids, has a high antioxidant ability, and could
      be considered as a functional food due to the presence of anthocyanins. 

PMID- 25961305
TI  - Does the type of event influence how user interactions evolve on Twitter?
AB  - The number of people using on-line social networks as a new way of communication
      is continually increasing. The messages that a user writes in these networks and
      his/her interactions with other users leave a digital trace that is recorded.
      Thanks to this fact and the use of network theory, the analysis of messages, user
      interactions, and the complex structures that emerge is greatly facilitated. In
      addition, information generated in on-line social networks is labeled
      temporarily, which makes it possible to go a step further analyzing the dynamics
      of the interaction patterns. In this article, we present an analysis of the
      evolution of user interactions that take place in television, socio-political,
      conference, and keynote events on Twitter. Interactions have been modeled as
      networks that are annotated with the time markers. We study changes in the
      structural properties at both the network level and the node level. As a result
      of this analysis, we have detected patterns of network evolution and common
      structural features as well as differences among the events. 

PMID- 25961306
TI  - Arthropod but not bird predation in ethiopian homegardens is higher in tree-poor
      than in tree-rich landscapes.
AB  - Bird and arthropod predation is often associated with natural pest control in
      agricultural landscapes, but the rates of predation may vary with the amount of
      tree cover or other environmental factors. We examined bird and arthropod
      predation in three tree-rich and three tree-poor landscapes across southwestern
      Ethiopia. Within each landscape we selected three tree-rich and three tree-poor
      homegardens in which we recorded the number of tree species and tree stems within
      100 * 100 m surrounding the central house. To estimate predation rates, we
      attached plasticine caterpillars on leaves of two coffee and two avocado shrubs
      in each homegarden, and recorded the number of attacked caterpillars for 7-9
      consecutive weeks. The overall mean daily predation rate was 1.45% for birds and
      1.60% for arthropods. The rates of arthropod predation varied among landscapes
      and were higher in tree-poor landscapes. There was no such difference for birds.
      Within landscapes, predation rates from birds and arthropods did not vary between
      tree-rich and tree-poor homegardens in either tree-rich or tree-poor landscapes.
      The most surprising result was the lack of response by birds to tree cover at
      either spatial scale. Our results suggest that in tree-poor landscapes there are
      still enough non-crop habitats to support predatory arthropods and birds to
      deliver strong top-down effect on crop pests. 

PMID- 25961307
TI  - Application of a hyaluronic acid gel after intrauterine surgery may improve
      spontaneous fertility: a randomized controlled trial in New Zealand White
      rabbits.
AB  - OBJECTIVE: Intrauterine adhesions (IUAs) are the most common complication after
      hysteroscopy in patients of reproductive age. Intra-abdominal anti-adhesion gel
      reduces the incidence of adhesions, but effects on fertility after uterine
      surgery are not known. The objective of our work was to evaluate the effect of
      intrauterine anti-adhesion gel on spontaneous fertility after repeated
      intrauterine surgery with induced experimental synechiae in the rabbit model.
      MATERIALS AND METHODS: Twenty New Zealand White rabbits underwent a double
      uterine curettage 10 days apart and were randomized into two groups. Each rabbit
      served as its own control: one uterine tube was the treatment group (A), the
      second uterine tube was the control group (B) to avoid bias through other causes
      of infertility. Group A received a post curettage intrauterine instillation of
      anti-adhesion gel whereas group B, the control group, underwent curettage without
      instillation of the gel. After a recovery period, the rabbits were mated. An
      abdominal ultrasound performed 21 days after mating allowed us to diagnose
      pregnancy and quantify the number of viable fetuses. RESULTS: There was a
      significant difference in total fetuses in favor of group A, with an average of
      3.7 (range, 0-9) total fetuses per tube against 2.1 (0-7) in group B (p = .04).
      The number of viable fetuses shows a trend in favor of group A, with an average
      of 3.4 (0-7) viable fetuses per tube against 1.9 (0-6) viable fetuses per tube in
      group B (p = .05). CONCLUSION: The use of immediate postoperative anti-adhesion
      gel improved fertility in an animal model after intrauterine surgery likely to
      cause uterine synechiae. This experimental model will permit comparison of
      different anti-adhesion solutions, including assessment of their tolerance and
      potential mucosal toxicity on embryonic development.

PMID- 25961308
TI  - Repurposing Non-Antimicrobial Drugs and Clinical Molecules to Treat Bacterial
      Infections.
AB  - There is a pressing need to develop novel antimicrobials to circumvent the
      scourge of antimicrobial resistance. The objective of this study is to identify
      non-antibiotic drugs with potent antimicrobial activity, within an applicable
      clinical range. A library, containing 727 FDA approved drugs and small molecules,
      was screened against ESKAPE pathogens (Enterococcus faecium, Staphylococcus
      aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa,
      and Enterobacter cloacae). Drugs that showed antimicrobial activity in an
      applicable clinical range were further tested in vitro and in vivo in an infected
      mouse model. The initial screening identified 24 non-antibiotic drugs and
      clinical molecules active against Gram-positive pathogens including methicillin-
      resistant S. aureus (MRSA) and vancomycin-resistant enterococcus (VRE) isolates.
      Two non-antibiotic drugs showed activity against Gram-negative pathogens. Among
      the active non-antibiotic drugs, only ebselen (EB) and 5-fluoro-2'-deoxyuridine
      (FdUrd), showed bactericidal activity, in an applicable clinical range, against
      multi-drug-resistant Staphylococcus isolates including MRSA, vancomycin-resistant
      S. aureus (VRSA), and vancomycin-intermediate S. aureus (VISA). The minimum
      inhibitory concentration at which 90% of clinical isolates of S. aureus were
      inhibited (MIC90) was found to be 0.25 and 0.0039mg/L for EB and FdUrd,
      respectively. Treatment with EB orally significantly increased mice survival in a
      lethal model of septicemic MRSA infection by (60%) compared to that of control.
      FdUrd oral and intraperitoneal treatment significantly enhanced mouse survival by
      60% and 100%, respectively. These data encourage screening and repurposing of non
      antibiotic drugs and clinical molecules to treat multidrug-resistant bacterial
      infections.

PMID- 25961309
TI  - Stress in romantic relationships and adolescent depressive symptoms: Influence of
      parental support.
AB  - It is well known that stressful life events can play a role in the development of
      adolescent depressive symptoms; however, there has been little research on
      romantic stress specifically. The relationship between romantic stress and
      depressive symptoms is particularly salient in adolescence, as adolescence often
      involves the onset of dating. This and other stressors are often dealt with in
      the context of the family. The present study examined the relationship between
      romantic stress and depressive symptoms both concurrently and prospectively,
      controlling for preexisting depressive symptoms. We then explored whether support
      from parents buffers the negative effects of romantic stress on depressive
      symptoms. In addition, the study sought to determine whether the benefits of
      support vary by parent and child gender. A community sample of 375 adolescents
      completed self-report measures of parental support (both maternal and paternal),
      romantic stress, and depressive symptoms. A behavioral measure of maternal
      support was also obtained. For boys and girls, romantic stress at age 15
      predicted depressive symptoms at ages 15 and 18, even when controlling for age 13
      depressive symptoms. Perceived maternal support buffered the stress-depressive
      symptom relationship for both genders at age 15, even when controlling for age 13
      depressive symptoms. Higher perceived paternal support was associated with lower
      adolescent depressive symptoms; however, it did not have a buffering effect.
      These results have implications for the development of effective family-centered
      methods to prevent the development of depressive symptoms in adolescents.

PMID- 25961310
TI  - Four decades of research on school bullying: An introduction.
AB  - This article provides an introductory overview of findings from the past 40 years
      of research on bullying among school-aged children and youth. Research on
      definitional and assessment issues in studying bullying and victimization is
      reviewed, and data on prevalence rates, stability, and forms of bullying behavior
      are summarized, setting the stage for the 5 articles that comprise this American
      Psychologist special issue on bullying and victimization. These articles address
      bullying, victimization, psychological sequela and consequences, ethical, legal,
      and theoretical issues facing educators, researchers, and practitioners, and
      effective prevention and intervention efforts. The goal of this special issue is
      to provide psychologists with a comprehensive review that documents our current
      understanding of the complexity of bullying among school-aged youth and
      directions for future research and intervention efforts.

PMID- 25961312
TI  - A relational framework for understanding bullying: Developmental antecedents and
      outcomes.
AB  - This article reviews current research on the relational processes involved in
      peer bullying, considering developmental antecedents and long-term consequences.
      The following themes are highlighted: (a) aggression can be both adaptive and
      maladaptive, and this distinction has implications for bullies' functioning
      within peer social ecologies; (b) developmental antecedents and long-term
      consequences of bullying have not been well-distinguished from the extant
      research on aggressive behavior; (c) bullying is aggression that operates within
      relationships of power and abuse. Power asymmetry and repetition elements of
      traditional bullying definitions have been hard to operationalize, but without
      these specifications and more dyadic measurement approaches there may be little
      rationale for a distinct literature on bullying--separate from aggression.
      Applications of a relational approach to bullying are provided using gender as an
      example. Implications for future research are drawn from the study of
      relationships and interpersonal theories of developmental psychopathology.

PMID- 25961311
TI  - Long-term adult outcomes of peer victimization in childhood and adolescence:
      Pathways to adjustment and maladjustment.
AB  - The study of peer victimization has drawn together researchers, parents,
      teachers, and health professionals around the world in an effort to make change.
      Research attention has focused on the question of whether peer victimization in
      childhood and adolescence leads to lasting and serious negative ramifications in
      the lives of young people. We consider the wealth of information documenting the
      troubling adjustment that follows peer victimization within childhood and
      adolescence. Findings from prospective studies tracking children and adolescents
      into young adulthood are presented and synthesized. Using the construct of
      "multifinality" as our framework, we explore why it might be that early peer
      victimization does not have the same impact on all young people by considering
      factors that place individuals at greater risk or appear to protect them from
      more lasting harm. In addition to a need for carefully planned prospective
      studies, the field would benefit from the use of qualitative studies aimed at
      elucidating possible causal, concurrent, and resultant mechanisms involved with
      victimization.

PMID- 25961313
TI  - Translating research to practice in bullying prevention.
AB  - Bullying continues to be a concern in schools and communities across the United
      States and worldwide, yet there is uncertainty regarding the most effective
      approaches for preventing it and addressing its impacts on children and youth.
      This paper synthesizes findings from a series of studies and meta-analyses
      examining the efficacy of bullying prevention programs. This paper considers some
      methodological issues encountered when testing the efficacy and effectiveness of
      bullying prevention and intervention approaches. It also identifies several areas
      requiring additional research in order to increase the effectiveness of bullying
      prevention efforts in real-world settings. Drawing upon a public health
      perspective and findings from the field of prevention science, this paper aims to
      inform potential future directions for enhancing the adoption, high quality
      implementation, and dissemination of evidence-based bullying prevention programs.
      It is concluded that although bullying prevention programs can be effective in
      reducing bullying and victimization among school-aged youth, there is a great
      need for more work to increase the acceptability, fidelity, and sustainability of
      the existing programs in order to improve bullying-related outcomes for youth.
      The findings from this review are intended to inform both policy and public
      health practice related to bullying prevention.

PMID- 25961314
TI  - Law and policy on the concept of bullying at school.
AB  - The nationwide effort to reduce bullying in U.S. schools can be regarded as part
      of larger civil and human rights movements that have provided children with many
      of the rights afforded to adult citizens, including protection from harm in the
      workplace. Many bullied children find that their schools are hostile
      environments, but civil rights protections against harassment apply only to
      children who fall into protected classes, such as racial and ethnic minorities,
      students with disabilities, and victims of gender harassment or religious
      discrimination. This article identifies the conceptual challenges that bullying
      poses for legal and policy efforts, reviews judicial and legislative efforts to
      reduce bullying, and makes some recommendations for school policy. Recognition
      that all children have a right to public education would be one avenue for
      broadening protection against bullying to all children.

PMID- 25961315
TI  - Understanding the psychology of bullying: Moving toward a social-ecological
      diathesis-stress model.
AB  - With growing recognition that bullying is a complex phenomenon, influenced by
      multiple factors, research findings to date have been understood within a social
      ecological framework. Consistent with this model, we review research on the known
      correlates and contributing factors in bullying/victimization within the
      individual, family, peer group, school and community. Recognizing the fluid and
      dynamic nature of involvement in bullying, we then expand on this model and
      consider research on the consequences of bullying involvement, as either victim
      or bully or both, and propose a social-ecological, diathesis-stress model for
      understanding the bullying dynamic and its impact. Specifically, we frame
      involvement in bullying as a stressful life event for both children who bully and
      those who are victimized, serving as a catalyst for a diathesis-stress connection
      between bullying, victimization, and psychosocial difficulties. Against this
      backdrop, we suggest that effective bullying prevention and intervention efforts
      must take into account the complexities of the human experience, addressing both
      individual characteristics and history of involvement in bullying, risk and
      protective factors, and the contexts in which bullying occurs, in order to
      promote healthier social relationships.

PMID- 25961316
TI  - Should Malpractice Settlements Be Secret?

PMID- 25961317
TI  - Highly effective NK cells are associated with good prognosis in patients with
      metastatic prostate cancer.
AB  - Clinical outcome of patients with metastatic prostate cancer (mPC) at diagnosis
      is heterogeneous and unpredictable; thus alternative treatments such as
      immunotherapy are investigated. We retrospectively analyzed natural killer (NK)
      cells by flow cytometry in peripheral blood from 39 mPC patients, with 5 year
      follow-up, and their correlation with time to castration resistance (TCR) and
      overall survival (OS). In parallel, NK functionality was carried out against
      prostate tumor cell lines, analyzed for the expression of NK cell ligands, to
      identify the receptors involved in PC recognition. NK cells from patients with
      longer TCR and OS displayed high expression of activating receptors and high
      cytotoxicity. The activating receptors NKp30 and NKp46 were the most obvious
      predictive markers of OS and TCR in a larger cohort of mPC patients (OS: p=
      0.0018 and 0.0009; TCR: p= 0.007 and < 0.0001 respectively, log-rank test).
      Importantly, blocking experiments revealed that NKp46, along with NKG2D and DNAM
      1 and, to a lesser extent NKp30, were involved in prostate tumor recognition by
      NK cells. These results identify NK cells as potential predictive biomarkers to
      stratify patients who are likely to have longer castration response, and pave the
      way to explore therapies aimed at enhancing NK cells in mPC patients. 

PMID- 25961318
TI  - Inter-chromosomal contact networks provide insights into Mammalian chromatin
      organization.
AB  - The recent advent of conformation capture techniques has provided unprecedented
      insights into the spatial organization of chromatin. We present a large-scale
      investigation of the inter-chromosomal segment and gene contact networks in
      embryonic stem cells of two mammalian organisms: humans and mice. Both
      interaction networks are characterized by a high degree of clustering of genome
      regions and the existence of hubs. Both genomes exhibit similar structural
      characteristics such as increased flexibility of certain Y chromosome regions and
      co-localization of centromere-proximal regions. Spatial proximity is correlated
      with the functional similarity of genes in both species. We also found a
      significant association between spatial proximity and the co-expression of genes
      in the human genome. The structural properties of chromatin are also species
      specific, including the presence of two highly interactive regions in mouse
      chromatin and an increased contact density on short, gene-rich human chromosomes,
      thereby indicating their central nuclear position. Trans-interacting segments are
      enriched in active marks in human and had no distinct feature profile in mouse.
      Thus, in contrast to interactions within individual chromosomes, the inter
      chromosomal interactions in human and mouse embryonic stem cells do not appear to
      be conserved. 

PMID- 25961319
TI  - Synthesis of highly efficient CaO-based, self-stabilizing CO2 sorbents via
      structure-reforming of steel slag.
AB  - Capturing anthropogenic CO2 in a cost-effective and highly efficient manner is
      one of the most challenging issues faced by scientists today. Herein, we report a
      novel structure-reforming approach to convert steel slag, a cheap, abundant, and
      nontoxic calcium-rich industrial waste, as the only feedstock into superior CaO
      based, self-stabilizing CO2 sorbents. The CO2 capture capacity of all the steel
      slag-derived sorbents was improved more than 10-fold compared to the raw slag,
      with the maximum uptake of CO2 achieving at 0.50 gCO2 gsorbent(-1). Additionally,
      the initial steel slag-derived sorbent could retain 0.25 gCO2 gsorbent(-1), that
      is, a decay rate of only 12% over 30 carbonation-calcination cycles, the
      excellent self-stabilizing property allowed it to significantly outperform
      conventional CaO, and match with most of the existing synthetic CaO-based
      sorbents. A synergistic effect that facilitated CO2 capture by CaO-based sorbents
      was clearly recognized when Mg and Al, the most common elements in steel slag,
      coexisted with CaO in the forms of MgO and Al2O3, respectively. During the
      calcium looping process, MgO served as a well spacer to increase the porosity of
      sorbents together with Al2O3 serving as a durable stabilizer to coresist the
      sintering of CaCO3 grains at high temperatures.

PMID- 25961320
TI  - Krill products: an overview of animal studies.
AB  - Many animal studies have been performed with krill oil (KO) and this review aims
      to summarize their findings and give insight into the mechanism of action of KO.
      Animal models that have been used in studies with KO include obesity, depression,
      myocardial infarction, chronic low-grade and ulcerative inflammation and are
      described in detail. Moreover, studies with KO in the form of krill powder (KP)
      and krill protein concentrate (KPC) as a mix of lipids and proteins are mentioned
      and compared to the effects of KO. In addition, differences in tissue uptake of
      the long-chain omega-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA)
      and docosahexaenoic acid (DHA), when delivered in either phospholipid or
      triglyceride form, are addressed and the differential impact the delivery form
      has on gene expression profiles is explained. In our outlook, we try to highlight
      the potential of KO and KP supplementation in clinical settings and discuss
      health segments that have a high potential of showing krill product specific
      health benefits and warrant further clinical investigations. 

PMID- 25961323
TI  - A Note of Caution on the Role of Halogen Bonds for Protein Kinase/Inhibitor
      Recognition Suggested by High- And Low-Salt CK2alpha Complex Structures.
AB  - CK2 is a Ser/Thr kinase recruited by tumor cells to avoid cell death. 4'-Carboxy
      6,8-dibromo-flavonol (FLC26) is a nanomolar CK2 inhibitor reducing the
      physiological phosphorylation of CK2 biomarkers and inducing cell death. Its
      binding mode to the ATP site was predicted to depend primarily on noncovalent
      interactions not comprising halogen bonds. We confirm this by two independent
      cocrystal structures which additionally show that FLC26 is selective for an open,
      protein kinase-untypical conformation of the hinge/helix alphaD region. The
      structures suggest how the bromo substituents, found previously in lead
      optimization studies, contribute to the inhibitory efficacy. In this context, one
      of the complex structures, obtained by crystallization with the kosmotropic salt
      NaCl, revealed an unconventional pi-halogen bond between the 8-bromo substituent
      of FLC26 and an aromatic side chain which is absent under low-salt conditions.
      The kosmotropic salt sensitivity of pi-halogen bonds is a novel feature which
      requires attention in structural comparisons and halogen-bond-based explanations.

PMID- 25961321
TI  - B-vitamins and bone health--a review of the current evidence.
AB  - Because of ongoing global ageing, there is a rapid worldwide increase in
      incidence of osteoporotic fractures and the resultant morbidity and mortality
      associated with these fractures are expected to create a substantial economic
      burden. Dietary modification is one effective approach for prevention of
      osteoporosis in the general population. Recently, B vitamins have been
      investigated for their possible roles in bone health in human studies. In this
      review, we provide different lines of evidence and potential mechanisms of
      individual B vitamin in influencing bone structure, bone quality, bone mass and
      fracture risk from published peer-reviewed articles. These data support a
      possible protective role of B vitamins, particularly, B2, B6, folate and B12, in
      bone health. However, results from the clinical trials have not been promising in
      supporting the efficacy of B vitamin supplementation in fracture reduction.
      Future research should continue to investigate the underlying mechanistic
      pathways and consider interventional studies using dietary regimens with vitamin
      B enriched foods to avoid potential adverse effects of high-dose vitamin B
      supplementation. In addition, observational and interventional studies conducted
      in Asia are limited and thus require more attention due to a steep rise of
      osteoporosis and hip fracture incidence projected in this part of the world. 

PMID- 25961324
TI  - Wall-generated pattern on a periodically excited miscible liquid/liquid
      interface.
AB  - We present a new generic type of pattern generated by bounding walls on the
      interface between miscible liquids in a horizontally vibrated cell. The pattern
      is observed in laboratory experiments and numerical simulations below and above
      the frozen-wave instability threshold. At the threshold, a competition develops
      between the new "fish-spine" pattern and frozen waves, while above the threshold
      these two kinds of patterns may coexist in spatially separated domains. We
      propose a theoretical model for the formation mechanism of the fish-spine pattern
      and its spreading along the interface. 

PMID- 25961322
TI  - Bones of contention: bone mineral density recovery in celiac disease--a
      systematic review.
AB  - Metabolic bone disease is a frequent co-morbidity in newly diagnosed adults with
      celiac disease (CD), an autoimmune disorder triggered by the ingestion of dietary
      gluten. This systematic review of studies looked at the efficacy of the gluten
      free diet, physical activity, nutrient supplementation, and bisphosphonates for
      low bone density treatment. Case control and cohort designs were identified from
      PubMed and other academic databases (from 1996 to 2015) that observed newly
      diagnosed adults with CD for at least one year after diet treatment using the
      dual-energy x-ray absorptiometry (DXA) scan. Only 20 out of 207 studies met the
      inclusion criteria. Methodological quality was assessed using the Strengthening
      of the Reporting of Observational Studies in Epidemiology (STROBE) statement
      checklist. Gluten-free diet adherence resulted in partial recovery of bone
      density by one year in all studies, and full recovery by the fifth year. No
      treatment differences were observed between the gluten-free diet alone and diet
      plus bisphosphonates in one study. For malnourished patients, supplementation
      with vitamin D and calcium resulted in significant improvement. Evidence for the
      impact of physical activity on bone density was limited. Therapeutic strategies
      aimed at modifying lifestyle factors throughout the lifespan should be studied. 

PMID- 25961326
TI  - Cultured construction: global evidence of the impact of national values on
      sanitation infrastructure choice.
AB  - Case study research often claims culture-variously defined-impacts infrastructure
      development. I test this claim using Hofstede's cultural dimensions and newly
      available data representing change in national coverage of sewer connections,
      sewerage treatment, and onsite sanitation between 1990 and 2010 for 21 developing
      nations. The results show that the cultural dimensions of uncertainty avoidance,
      masculinity-femininity, and individualism-collectivism have statistically
      significant relationships to sanitation technology choice. These data prove the
      global impact of culture on infrastructure choice, and reemphasize that local
      cultural preferences must be considered when constructing sanitation
      infrastructure.

PMID- 25961325
TI  - Iron superoxide dismutases in eukaryotic pathogens: new insights from Apicomplexa
      and Trypanosoma structures.
AB  - Prior studies have highlighted the potential of superoxide dismutases as drug
      targets in eukaryotic pathogens. This report presents the structures of three
      iron-dependent superoxide dismutases (FeSODs) from Trypanosoma cruzi, Leishmania
      major and Babesia bovis. Comparison with existing structures from Plasmodium and
      other trypanosome isoforms shows a very conserved overall fold with subtle
      differences. In particular, structural data suggest that B. bovis FeSOD may
      display similar resistance to peroxynitrite-mediated inactivation via an
      intramolecular electron-transfer pathway as previously described in T. cruzi
      FeSOD isoform B, thus providing valuable information for structure-based drug
      design. Furthermore, lysine-acetylation results in T. cruzi indicate that
      acetylation occurs at a position close to that responsible for the regulation of
      acetylation-mediated activity in the human enzyme. 

PMID- 25961327
TI  - Role of Cooperative Interactions in the Intercalation of Heteroatoms between
      Graphene and a Metal Substrate.
AB  - The intercalation of heteroatoms between graphene and a metal substrate has been
      studied intensively over the past few years, due to its effect on the graphene
      properties, and as a method to create vertical heterostructures. Various
      intercalation processes have been reported with different combinations of
      heteroatoms and substrates. Here we study Si intercalation between graphene and
      Ru(0001). We elucidate the role of cooperative interactions between hetero-atoms,
      graphene, and substrate. By combining scanning tunneling microscopy with density
      functional theory, the intercalation process is confirmed to consist of four key
      steps, involving creation of defects, migration of heteroatoms, self-repairing of
      graphene, and growth of an intercalated monolayer. Both theory and experiments
      indicate that this mechanism applies also to other combinations of hetero-atoms
      and substrates. 

PMID- 25961328
TI  - Nazumazoles A-C, Cyclic Pentapeptides Dimerized through a Disulfide Bond from the
      Marine Sponge Theonella swinhoei.
AB  - A mixture of nazumazoles A-C (1-3) was purified from the extract of the marine
      sponge Theonella swinhoei. The mixture was eluted as an extraordinarily broad
      peak in the reversed-phase HPLC. The structures of nazumazoles were determined by
      interpretation of the NMR data and chemical degradations. Nazumazoles contain one
      residue each of alanine-derived oxazole and alpha-keto-beta-amino acid residue.
      Nazumazoles exhibited cytotoxicity against P388 cells. 

PMID- 25961329
TI  - Visible and ultraviolet spectroscopy of gas phase rhodamine 575 cations.
AB  - The visible and ultraviolet spectroscopy of gas phase rhodamine 575 cations has
      been studied experimentally by action-spectroscopy in a modified linear ion trap
      between 220 and 590 nm and by time-dependent density functional theory (TDDFT)
      calculations. Three bands are observed that can be assigned to the electronic
      transitions S0 -> S1, S0 -> S3, and S0 -> (S8,S9) according to the theoretical
      prediction. While the agreement between theory and experiment is excellent for
      the S3 and S8/S9 transitions, a large shift in the value of the calculated S1
      transition energy is observed. A theoretical analysis of thermochromism,
      potential vibronic effects, and-qualitatively-electron correlation revealed it is
      mainly the latter that is responsible for the failure of TDDFT to accurately
      reproduce the S1 transition energy, and that a significant thermochromic shift is
      also present. Finally, we investigated the nature of the excited states by
      analyzing the excitations and discussed their different fragmentation behavior.
      We hypothesize that different contributions of local versus charge transfer
      excitations are responsible for 1-photon versus 2-photon fragmentation observed
      experimentally. 

PMID- 25961330
TI  - Si Radial p-i-n Junction Photovoltaic Arrays with Built-In Light Concentrators.
AB  - High-performance photovoltaic (PV) devices require strong light absorption, low
      reflection and efficient photogenerated carrier collection for high quantum
      efficiency. Previous optical studies of vertical wires arrays have revealed that
      extremely efficient light absorption in the visible wavelengths is achievable.
      Photovoltaic studies have further advanced the wire approach by employing radial
      p-n junction architectures to achieve more efficient carrier collection. While
      radial p-n junction formation and optimized light absorption have independently
      been considered, PV efficiencies have further opportunities for enhancement by
      exploiting the radial p-n junction fabrication procedures to form arrays that
      simultaneously enhance both light absorption and carrier collection efficiency.
      Here we report a concept of morphology control to improve PV performance, light
      absorption and quantum efficiency of silicon radial p-i-n junction arrays.
      Surface energy minimization during vapor phase epitaxy is exploited to form match
      head structures at the tips of the wires. The match-head structure acts as a
      built-in light concentrator and enhances optical absorptance and external quantum
      efficiencies by 30 to 40%, and PV efficiency under AM 1.5G illumination by 20%
      compared to cylindrical structures without match-heads. The design rules for
      these improvements with match-head arrays are systematically studied. This
      approach of process-enhanced control of three-dimensional Si morphologies
      provides a fab-compatible way to enhance the PV performance of Si radial p-n
      junction wire arrays. 

PMID- 25961331
TI  - Survival advantage of women in localized melanoma mainly relies on clinical
      pathological differences by sex. A retrospective study of 1,607 patients in
      Valencia, Spain.
AB  - BACKGROUND: Among melanoma patients, women have a better prognosis than men but
      the differences might be due to a different presentation of melanoma. OBJECTIVES:
      The aim of this study was to identify differences in clinical presentation and
      survival in cutaneous melanoma between men and women in a Spanish population
      stratified by age. MATERIALS & METHODS: In total, 1,607 consecutive patients with
      localized cutaneous melanoma and complete clinical and pathological information
      were evaluated. Average follow-up was 5 years. Patients were stratified by age
      into three groups: <= 45 years, 46-60 years, and >60 years. Disease-free
      survival, overall-survival and disease-specific survival were generated using the
      Kaplan-Meier method. Multivariate survival analyses were evaluated using Cox
      modelling. RESULTS: Melanoma presented more frequently in the trunk in male
      patients and in the lower extremities and acral location in female patients. Men
      presented thicker tumors than women. However, for histological type, mitotic rate
      and ulceration there were no significant differences between the sexes. In the
      univariate survival analyses, women showed better disease-free, overall and
      disease-specific survival in the younger age group, compared with males of the
      same group. After adjusting for anatomical site, Breslow thickness, mitotic rate
      and presence of ulceration, there were no differences between males and females
      in any of the three age groups. CONCLUSION: The superior survival for women over
      men did not persist after adjusting for multiple prognostic variables such as
      anatomical site, Breslow thickness, mitotic rate and ulceration.

PMID- 25961332
TI  - Determination of neonicotinoid insecticides and strobilurin fungicides in
      particle phase atmospheric samples by liquid chromatography-tandem mass
      spectrometry.
AB  - A liquid chromatography-tandem mass spectrometry method has been developed for
      the determination of neonicotinoids and strobilurin fungicides in the particle
      phase fraction of atmosphere samples. Filter samples were extracted with
      pressurized solvent extraction, followed by a cleanup step with solid phase
      extraction. Method detection limits for the seven neonicotinoid insecticides and
      six strobilurin fungicides were in the range of 1.0-4.0 pg/m(3). Samples were
      collected from June to September 2013 at two locations (Osoyoos and Oliver) in
      the southern Okanagan Valley Agricultural Region of British Columbia, where these
      insecticides and fungicides are recommended for use on tree fruit crops (apples,
      pears, cherries, peaches, apricots) and vineyards. This work represents the first
      detection of acetamiprid, imidacloprid, clothianidin, kresoxim-methyl,
      pyraclostrobin, and trifloxystrobin in particle phase atmospheric samples
      collected in the Okanagan Valley in Canada. The highest particle phase
      atmospheric concentrations were observed for imidacloprid, pyraclostrobin, and
      trifloxystrobin at 360.0, 655.6, and 1908.2 pg/m(3), respectively. 

PMID- 25961333
TI  - Particle and Energy Pair and Triplet Correlations in Liquids and Liquid Mixtures
      from Experiment and Simulation.
AB  - Recent advances in fluctuation solution theory (FST) have provided access to
      information concerning triplet fluctuations and integrals, in addition to the
      established pair fluctuations and integrals, for liquids and liquid mixtures
      using both experimental and simulation data. Here, FST is used to investigate
      pair and triplet correlations for (i) pure water as provided by experiment and
      simulation using both polarizable and nonpolarizable water models, (ii) liquid
      mixtures of methanol and water as provided by experiment and simulation, and
      (iii) native and denatured states of proteins as provided by simulation. The last
      application is particularly powerful, as it provides exact equations for the
      volume, enthalpy, compressibility, thermal expansion, and heat capacity of a
      single protein form provided by a single simulation. In addition, a discussion of
      the quality of the integrals obtained from experiment and simulation is provided.
      The results clearly illustrate that FST can be a powerful tool for the analysis
      and interpretation of both experimental and simulation data in complex liquid
      mixtures, including biomolecular systems, and that current simulation protocols
      can provide reliable values for the pair and triplet correlations and integrals. 

PMID- 25961335
TI  - General Reagent Free Route to pH Responsive Polyacryloyl Hydrazide Capped Metal
      Nanogels for Synergistic Anticancer Therapeutics.
AB  - Herewith, we report a facile synthesis of pH responsive polyacryloyl hydrazide
      (PAH) capped silver (Ag) or gold (Au) nanogels for anticancer therapeutic
      applications. A cost-effective instant synthesis of PAH-Ag or PAH-Au
      nanoparticles (NPs) possessing controllable particle diameter and narrow size
      distribution was accomplished by adding AgNO3 or AuCl to the aqueous solution of
      PAH under ambient conditions without using any additional reagent. PAH possessing
      carbonyl hydrazide pendant functionality served as both reducing and capping
      agent to produce and stabilize the NPs. The stability analysis by UV-vis, dynamic
      light scattering, and transmission electron microscopy techniques suggested that
      these NPs may be stored in a refrigerator for at least up to 2 weeks with
      negligible change in conformation. The average hydrodynamic size of PAH-Ag NPs
      synthesized using 0.2 mmol/L AgNO3 changed from 122 to 226 nm on changing the pH
      of the medium from 5.4 to 7.4, which is a characteristic property of pH
      responsive nanogel. Camptothecin (CPT) with adequate loading efficiency (6.3%)
      was encapsulated in the PAH-Ag nanogels. Under pH 5.4 conditions, these nanogels
      released 78% of the originally loaded CPT over a period of 70 h. The
      antiproliferative potential of PAH-Ag-CPT nanogels (at [CPT]=0.6 MUg/mL) against
      MCF-7 breast adeno-carcinoma cells were ~350% higher compared to that of the free
      CPT as evidenced by high cellular internalization of these nanogels. Induction of
      apoptosis in MCF-7 breast adeno-carcinoma cells by PAH-Ag-CPT nanogels was
      evidenced by accumulation of late apoptotic cell population. Drug along with the
      PAH-Ag NPs were also encapsulated in a pH responsive hydrogel through in situ
      gelation at room temperature using acrylic acid as the cross-linker. The
      resulting hydrogel released quantitative amounts of both drug and PAH-Ag NPs over
      a period of 16 h. The simplicity of synthesis and ease of drug loading with
      efficient release render these NPs a viable candidate for various biomedical
      applications, and moreover this synthetic procedure may be extended to other
      metal NPs.

PMID- 25961336
TI  - Pseudomonas fluorescens LBUM223 Increases Potato Yield and Reduces Common Scab
      Symptoms in the Field.
AB  - Common scab of potato, caused by pathogenic Streptomyces spp., is an important
      disease not efficiently controlled by current methods. We previously demonstrated
      that Pseudomonas fluorescens LBUM223 reduces common scab development under
      controlled conditions through phenazine-1-carboxylic (PCA) production, leading to
      reduced thaxtomin A production by the pathogen, a key pathogenicity and virulence
      factor. Here, we aimed at determining if LBUM223 is able to increase potato yield
      and control common scab under field conditions, while characterizing the
      biocontrol mechanisms involved. We investigated if a reduction in pathogen soil
      populations, activation of induced systemic resistance in potato, and/or changes
      in txtA gene expression, involved in thaxtomin A biosynthesis in pathogenic
      Streptomyces spp. were involved in common scab control by LBUM223. Common scab
      symptoms were significantly reduced and total tuber weight increased by 46% using
      biweekly applications of LBUM223. LBUM223 did not reduce pathogen soil
      populations, nor was potato systemic defense-related gene expression
      significantly altered between treatments. However, a significant down-regulation
      of txtA expression occurred in the geocaulosphere. This is the first
      demonstration that a Pseudomonas strain can directly alter the transcriptional
      activity of a key pathogenesis gene in a plant pathogen under field conditions,
      contributing to disease control. 

PMID- 25961334
TI  - Structure-Activity Relationship and Pharmacokinetic Studies of 1,5
      Diheteroarylpenta-1,4-dien-3-ones: A Class of Promising Curcumin-Based Anticancer
      Agents.
AB  - Forty-three 1,5-diheteroaryl-1,4-pentadien-3-ones were designed as potential
      curcumin mimics, structurally featuring a central five-carbon dienone linker and
      two identical nitrogen-containing aromatic rings. They were synthesized using a
      Horner-Wadsworth-Emmons reaction as the critical step and evaluated for their
      cytotoxicity and antiproliferative activities toward both androgen-insensitive
      and androgen-sensitive prostate cancer cell lines and an aggressive cervical
      cancer cell line. Most of the synthesized compounds showed distinctly better in
      vitro potency than curcumin in the four cancer cell lines. The structure-activity
      data acquired from the study validated (1E,4E)-1,5-dihereroaryl-1,4-pentadien-3
      ones as an excellent scaffold for in-depth development for clinical treatment of
      prostate and cervical cancers. 1-Alkyl-1H-imidazol-2-yl, ortho pyridyl, 1-alkyl
      1H-benzo[d]imidazole-2-yl, 4-bromo-1-methyl-1H-pyrazol-3-yl, thiazol-2-yl, and 2
      methyl-4-(trifluoromethyl)thiazol-5-yl were identified as optimal heteroaromatic
      rings for the promising in vitro potency. (1E,4E)-1,5-Bis(2-methyl-4
      (trifluoromethyl)thiazol-5-yl)penta-1,4-dien-3-one, featuring thiazole rings and
      trifluoromethyl groups, was established as the optimal lead compound because of
      its good in vitro potency and attractive in vivo pharmacokinetic profiles. 

PMID- 25961337
TI  - Variability of Potato virus Y in Tomato Crops in Poland and Development of a
      Reverse-Transcription Loop-Mediated Isothermal Amplification Method for Virus
      Detection.
AB  - A collection of 147 Potato virus Y (PVY) isolates from tomato, originating from
      several commercial fields and greenhouses in different regions of Poland, was
      tested for the presence of PVY by reverse-transcription polymerase chain
      reaction. However, in some cases, the results obtained were ambiguous. Therefore,
      a sensitive reverse-transcription loop-mediated isothermal amplification method
      was developed for rapid detection of PVY isolates. Phylogenetic and recombination
      analyses were performed based on sequences of the coat protein gene. In
      comparison with results obtained in 2008, the presence of other strains besides
      PVY(N)Wi-P was confirmed. A novel recombinant between PVY(NTN) and PVY(N)Wi-P
      strains was detected. Our results indicate an increasing distribution and
      variability of the PVY population on tomato in Poland. 

PMID- 25961339
TI  - Steroids, spinal cord and pain sensation.
AB  - During the whole life, the nervous system is continuously submitted to the
      actions of different categories of hormones, including steroids. Therefore, the
      interactions between hormonal compounds and neural tissues are subjected to
      intense investigations. While a majority of studies focus on the brain, the
      spinal cord (SC) has received little attention, although this structure is also
      an important part of the central nervous system, controlling motor and sensory
      functions. To point out the importance of interactions between hormones and the
      SC in the regulation of neurobiological activities, we recapitulated and
      discussed herein various key data, revealing that the pivotal role played by the
      SC in nociception and pain modulation, directly depends on the SC ability to
      metabolize and synthesize steroidal molecules. The paper suggests that future
      investigations aiming to develop effective strategies against chronic pain, must
      integrate regulatory effects exerted by hormonal steroids on the SC activity, as
      well as the actions of endogenous neurosteroids locally synthesized in spinal
      neural networks. 

PMID- 25961338
TI  - History and Diversity of Citrus leprosis virus Recorded in Herbarium Specimens.
AB  - Leprosis refers to two diseases of citrus that present similar necrotic local
      lesions, often surrounded by chlorotic haloes on citrus. Two distinct viruses are
      associated with this disease, one that produces particles primarily in the
      nucleus of infected plant cells (Citrus leprosis virus nuclear type [CiLV-N];
      Dichorhavirus) and another type that produces particles in the cytoplasm of
      infected plant cells (Citrus leprosis virus cytoplasmic type [CiLV-C];
      Cilevirus). Both forms are transmitted by Brevipalpid mites and have bipartite,
      single-stranded, RNA genomes. CiLV-C and CiLV-N are present in South and Central
      America and as far north as parts of Mexico. Although leprosis disease was
      originally described from Florida, it disappeared from there in the 1960s. The
      United States Department of Agriculture-Agricultural Research Service maintains
      preserved citrus specimens identified at inspection stations 50 or more years ago
      with symptoms of citrus leprosis. We isolated RNA from these samples and
      performed degradome sequencing. We obtained nearly full-length genome sequences
      of both a typical CiLV-C isolate intercepted from Argentina in 1967 and a
      distinct CiLV-N isolate obtained in Florida in 1948. The latter is a novel form
      of CiLV-N, not known to exist anywhere in the world today. We have also
      documented the previously unreported presence of CiLV-N in Mexico in the mid-20th
      century. 

PMID- 25961340
TI  - Membrane-initiated signaling of estrogen related to neuroprotection. "Social
      networks" are required.
AB  - Numerous studies indicate that estrogens are crucial in normal brain functioning
      and preservation against different injuries. At the neuronal membrane, estrogens,
      binding to estrogen receptors (ERs) or other surface targets, exert rapid actions
      involving a plethora of signaling pathways that may converge in neuronal
      survival. Emerging work reveals that at least part of these actions may require
      the compartmentalization of ERs in signaling platforms, composed of
      macromolecular signaling proteins and particular lipid composition integrated in
      lipid rafts. These particular microstructures may provide the optimal
      microenvironment to trigger multiple ER interactions that may be crucial for
      neuroprotection against different brain impairments, such as Alzheimer's disease
      (AD). In this order of ideas, recent evidence has demonstrated that a membrane ER
      (mER) physically interacts with a voltage-dependent anion channel (VDAC) in lipid
      rafts from septal, hippocampal and cortical neurons, and these interactions may
      have important consequences in the alternative mechanisms developed by estrogens
      to achieve neuroprotection against amyloid beta (Abeta)-induced toxicity. This
      review includes a survey of some of the rapid mechanisms developed by estrogen to
      prevent neuronal death, and the ER interactions that are involved in the
      structural maintenance and signal transduction mechanisms important for neuronal
      survival against AD neuro-pathology. A special emphasis is put on the biological
      relevance of neuronal membrane VDAC in Abeta-related neurotoxicity, and the
      potential modulation of this channel as a part of a signaling complex with mER,
      which may be modified in AD brains. 

PMID- 25961341
TI  - Neurosteroids in clinical practice: implications for women's health.
AB  - The steroidogenic endocrine glands and local synthesis both contribute to the
      pool of steroids present in the central nervous system (CNS) and peripheral
      nervous system (PNS). Although the synthesis of neurosteroids in the nervous
      system is now well established, the spectrum of respective functions in
      regulating neuronal and glial functions remains to be fully elucidated. From the
      concept of neurosteroids derives another therapeutical strategy: the use of
      pharmaceutical agents that increase the synthesis of endogenous neurosteroids
      within the nervous system. This approach is so far hampered by the lack of
      knowledge concerning the regulation of the biosynthetic pathways of neurosteroids
      and their relationship with sex steroids produced by peripheral glands. The
      present review summarizes some of the available clinical and experimental
      findings supporting the critical role of neuro-steroids during the fertile life
      and reproductive aging and their relationship with endogenous and exogenous sex
      steroids. Brain metabolism of synthethic progestins and the implication of
      dehydroepiandrosterone (DHEA) treatment in post-menopausal women will be also
      discussed. 

PMID- 25961342
TI  - Induced testosterone deficiency: from clinical presentation of fatigue, erectile
      dysfunction and muscle atrophy to insulin resistance and diabetes.
AB  - Over the past 60 years, androgen deprivation therapy has been the mainstay of
      treatment of metastatic prostate cancer. However, research findings suggest that
      androgen deprivation therapy inflicts serious adverse effects on overall health
      and reduces the quality of life. Among the adverse effects known to date are
      insulin resistance, diabetes, metabolic syndrome fatigue, erectile dysfunction,
      and cardiovascular disease. In this clinical perspective, we discuss the
      relationship between induced androgen deficiency and a host of pathologies in the
      course of treatment with androgen deprivation therapy for prostate cancer
      patients. 

PMID- 25961343
TI  - Androgen deficiency and mitochondrial dysfunction: implications for fatigue,
      muscle dysfunction, insulin resistance, diabetes, and cardiovascular disease.
AB  - Among the major physiological functions of steroid hormones is regulation of
      carbohydrate, fat, and protein metabolism. Mitochondria, through oxidative
      phosphorylation, play a critical role in modulating a host of complex cellular
      metabolic pathways to produce chemical energy to meet the metabolic demand for
      cellular function. Thus, androgens may regulate cellular metabolism and energy
      production by increased mitochondrial numbers, activation of respiratory chain
      components, and increased transcription of mitochondrial-encoded respiratory
      chain genes that code for enzymes responsible for oxidative phosphorylation.
      Androgen deficiency is associated with increased insulin resistance, type 2
      diabetes (T2DM), metabolic syndrome, obesity, and increased overall mortality.
      One common link among all these pathologies is mitochondrial dysfunction.
      Contemporary evidence exists suggesting that testosterone deficiency (TD)
      contributes to mitochondrial dysfunction, including structural alterations and
      reduced expression and activities of metabolic enzymes. Here, we postulate that
      TD contributes to symptoms of fatigue, insulin resistance, T2DM, cardiovascular
      risk, and metabolic syndrome through a common mechanism involving impairment of
      mitochondrial function. 

PMID- 25961344
TI  - Managing immunity in resistant cancer patients correlates to survival: results
      and discussion of a pilot study.
AB  - Many cancer patients do not die due to impaired organ functions, but as a result
      of reduced general conditions, such as cachexia, sarcopenia, depression,
      infections, or stress. Reduced general health may be caused by immune modifying
      cytokines released from the tumor into the body. Improvement of immunity would
      not only reduce cancer side effects through inhibiting cytokine release from the
      tumor into the blood, but also, according to a new hypothesis, modify the cancer
      stem cells (CSC) in the tumor, which are believed to drive cancer growth and
      metastasis. We reported previously several investigations with a dietary
      fermented soy formulation (FSWW08) in cancer patients, where we saw a) strong
      reduction of cancer symptoms, b) broken resistance to chemotherapy, and c) a
      strong reduction of chemotherapy's toxic side effects, when taken in combination.
      This publication reports two new findings from a pilot study with postsurgical,
      treatment resistant patients conducted over four years. First, neither treatment
      resistance nor side effects were observed. Second, more patients have survived
      than expected. The improved health and immunity is detected together with
      increased CSC differentiation, suggesting lower aggressiveness, which was
      corroborated by increased gene expressions, particularly of steroidal hormones,
      MAPkinase, NF-kappaB, and tumor suppressor factor p53, a typical marker of
      "stemness" or cell differentiation. Although limited by its small, homogenous
      sample size, the results of this pilot study illustrate the relationship between
      CSCs differentiation, and the clinical symptoms of immunity, which influence
      survival outcomes and raise the clinical potential of measuring CSCs in ovarian,
      prostate, and breast cancers. The improved survival rates are also seen in larger
      cohort studies, which show similar gene expression profiles, which were induced
      by FSWW08 in the treatment resistant cancer patients in this study. 

PMID- 25961345
TI  - Liver X receptor agonist downregulates growth hormone signaling in the liver.
AB  - Liver X receptor (LXR) agonists have been shown to influence the development of
      hyperlipidemia and atherosclerosis in mouse models. It has also been demonstrated
      that some LXR agonists can cause hepatic steatosis in experimental animals.
      Growth hormone (GH) is known to regulate hepatic metabolism and the absence of
      hepatic GH receptors (GHR) leads to hepatic steatosis. In this study, we analyzed
      whether the actions of LXR agonists could involve interference with GH signaling.
      We showed that LXR agonists impair GH signaling in hepatocytes. LXR agonist
      treatment attenuated GH induction of suppressor of cytokine signaling 2 (SOCS2),
      SOCS3, and CIS mRNA levels in BRL-4 cells. Likewise, the activity of a luciferase
      reporter vector driven by the GH response element (GHRE) of the SOCS2 gene was
      inhibited by simultaneous treatment with an LXR agonist. The inhibitory effect of
      LXR agonists on GH signals can be mimicked by overexpression of the LXR regulated
      factors, sterol regulatory element binding protein 1 (SREBP1) and SREBP2, in
      hepatic cells. In both cases total and phosphorylated signal transducers and
      activators of transcription 5b (STAT5b) protein levels were significantly
      reduced. DNA binding assays demonstrated that SREBP1 binds to an E-box within a
      previously defined GHRE in the SOCS2 gene promoter, but does not compete with
      STAT5b binding to a nearby site in the same promoter construct. Taken together,
      our findings indicate that the inhibitory effects of LXR agonists on GH signaling
      are mediated by SREBP1, through the downregulation of STAT5b gene transcription
      and stimulation of STAT5b protein degradation. The findings provide a new insight
      into the understanding of the molecular actions of LXR agonists, which may be of
      relevance to their pharmacological actions. 

PMID- 25961346
TI  - Hormone replacement therapy: 1815.84 woman-years of follow-up main clinical
      events.
AB  - BACKGROUND: One hundred and eighty-five women with a mean age of 50.71 (SD=5.58)
      years upon initiation of treatment were studied before, and during, treatment.
      MATERIALS AND METHODS: Included in the profile of patients under study were
      family and personal histories, gynecological and breast examinations. Population
      age: a) <60 years old, 171 women (92.43%), and b) aged 60 years or older, 14
      women (7.57%). Dosage comprised both 0.625 mg/daily orally of conjugated equine
      estrogens and 2.5 or 5 mg/daily of medroxy progesterone acetate. No further
      specific treatment was prescribed. Mean duration of treatment was 9.82 (SD=5.42)
      years for all women; 9.70 (SD=5.44) in the younger group. Follow-up comprised
      1815.84 woman-years, for 5 years or over (76.75%) on 142 women. Fifty-two women
      (28.11%) dropped out. RESULTS: No deaths occurred during treatment. Four
      cardiovascular events (2.16%) were reported. No spontaneous bone fracture was
      documented. Nonetheless, there were 12 bone fractures of traumatic origin
      (6.48%), none of them hip fractures. Five breast cancers were observed. Likewise,
      one diagnosis of breast cancer for every 37 treated women from our series was
      evidenced. There were 117 women (63.24%) without any events. CONCLUSION: A higher
      risk of breast cancer or of serious cardiovascular events cannot be inferred from
      statistical analysis of 5 years or more of treatment.

PMID- 25961347
TI  - Effect of tibolone and its principal metabolites (3alpha- and 3beta-hydroxy,
      3alpha-sulfate, and 4-ene derivatives) on estrone sulfatase activity in normal
      and cancerous human breast tissue.
AB  - BACKGROUND: Tibolone (Org-OD14) is the active substance of Livial(r), a synthetic
      steroid with the structure 7alpha,17alpha-17-hydroxy-7-methyl-19-norpregn-5(10)
      en-20-yn-3-one, possessing weak tissue-specific estrogenic, progestogenic, and
      androgenic properties, used to treat menopausal complaints. After oral
      administration, tibolone is extensively metabolized into the 3alpha-(Org-4904)
      and 3beta-(Org-30126) hydroxy derivatives with estrogenic properties, its 4-ene
      (Org-OM38) isomer with progestogenic/androgenic activities, and the 3alpha
      sulfate (Org-34322) derivative, a major biologically inactive circulating form.
      We compared the dose response of tibolone and its metabolites on estrone
      sulfatase activity [conversion of estrone sulfate (E1S) to estrone (E1)] in
      normal and cancerous human breast tissues. MATERIALS AND METHODS: Tissue minces
      were incubated with physiological concentrations of [3H]-E1S (5*10-9M) alone or
      in the presence of tibolone and its metabolites (concentration range: 5*10-7to
      5*10-5M) for 4 h. Tritiated E1, estradiol (E2), and E1S were separated and
      evaluated quantitatively by thin-layer chromatography. RESULTS: The sulfatase
      activity was significantly higher in cancerous breast but strongly inhibited by
      tibolone and the different metabolites, whereas 3alpha- and 3beta-hydroxy
      derivatives were the most potent inhibitors. CONCLUSION: This very significant
      inhibitory effect of tibolone and its principal metabolites on the enzyme
      involved in E2biosynthesis in the human breast provides interesting perspectives
      to study the biological responses of these compounds in trials with breast cancer
      patients.

PMID- 25961348
TI  - Evaluation of dysthyronemia in endocrinological patients.
AB  - BACKGROUND: Dysthyronemia is the state of the thyroid gland in which the
      concentration of thyrotropin (TSH) in circulation is within the reference range,
      but the concentrations of free or total fractions of thyroid hormones (TH) are
      outside the reference range. Normal values of TSH and increased values of TH are
      referred to as hyperthyroxinemia or hypertriiodothyroninemia, while normal values
      of TSH and decreased values of TH are called hypothyroxinemia or
      hypotriiodothyroninemia. METHODS: Thyroid diagnostic tests were carried out at
      the Institute of Endocrinology, Prague, Czech Republic, in 1999-2009 using the
      immunoanalytical systems of Roche Diagnostics GmbH, Germany (Elecsys 2010,
      Modular E170). RESULTS: Hyperthyroxinemia was found in 6.74% of all parallel sets
      of TSH and free thyroxine (FT4, n=259,590) values. Hypotriiodothyroninemia was
      observed in 8.48% of all parallel sets of TSH and total triiodothyronine (TT3,
      n=73,143). The occurrence of hyperthyroxinemia (TSH-FT4) and
      hypotriiodothyroninemia (TSH-TT3) was >3 times higher than the occurrence of
      dysthyronemia for the combinations TSH-FT4 (hypothyroxinemia), TSH-TT4 (total
      thyroxine, n=1996), TSH-FT3 (free triiodothyronine, n=94,090), and TSH-TT3
      (hypertrijodthyroninemia), and >5 times higher in comparison with the
      combinations TSH-FT4-FT3 (n=93,683), TSH-FT4-TT3 (n=72,373), TSH-FT3-TT3
      (n=2466), TSH-TT4-TT3 (n=1779), TSH-FT4-TT4 (n=1571), and TSH-FT3-TT4 (n=1466).
      CONCLUSION: In light of our patient types, we are assuming that the observed
      hypotriiodothyroninemia (TSH-TT3, 8.48%) is due to a decreased concentration of
      thyroid binding globulin in postmenopausal women and that hyperthyroxinemia (TSH
      FT4, 6.74%) is caused mainly by endogenous autoantibodies against thyroxine in
      patients with thyroid autoimmune diseases.

PMID- 25961349
TI  - Hormones in normal and cancerous breast: basic and clinical applications.

PMID- 25961350
TI  - Molecular basis of pregnancy-induced breast cancer prevention.
AB  - Reduction in breast cancer risk is associated with elevated circulating levels of
      human chorionic gonadotropin (hCG) during the first trimester of gestation. The
      knowledge that hCG also modifies the genomic signature of breast epithelial
      cells, from highly susceptible to refractory, to undergo neoplastic
      transformation, and also exerts both preventive and therapeutic effects on
      chemically induced mammary cancer, lead us to select this hormone for inducing
      chromatin remodeling in breast epithelial cells as a surrogate end point of
      complete differentiation and cancer prevention. We have found that chromatin
      remodeling is the driving force of the differences between the nulliparous and
      parous breast. In the parous breast, the epithelial cells have a condensed
      chromatin and increased reactivity with anti-H3K9me2 [di-methyl histone 3 (H3)
      (Lysine 9)] and H3K27me3 antibodies. This is accompanied by upregulation of
      noncoding RNA (ncRNA) elements including X2-inactive specific transcript (XIST)
      and chromatin remodeling genes, such as chromodomain helicase DNA-binding protein
      2 (CHD2) and the chromobox homolog 3 (CBX3), whose products are required for
      controlling recruitment of protein/protein or DNA/protein interactions Another
      important gene upregulated in the parous breast epithelial cells is the histone
      lysine N-methyltransferase or enhancer of zeste homolog 2 (EZH2), a member of the
      polycomb group (PcG) forming multimeric protein complexes that maintains the
      transcriptional repressive state of genes over successive cell generations. The
      fact that recent studies indicate that ncRNAs recruit PcG complexes to the locus
      of transcription or to sites located elsewhere in the genome cause us to
      postulate that the increased chromatin condensation in the parous breast has been
      initiated by ncRNAs, a postulate supported by the observed upregulation of
      several ncRNAs that included the XIST. The identification of a specific genomic
      signature of pregnancy has uncovered a novel tool that will serve as a surrogate
      biomarker for testing new chemopreventive agents and will significantly advance
      the field of cancer prevention. The clinical impact of this work is that it
      validates in an experimental system the genomic signature of prevention
      identified in the human parous breast and establish the bases for the use of the
      hormone hCG in the prevention of breast cancer, an approach that has not been
      fully developed until now. 

PMID- 25961351
TI  - Pregnancy hormonal environment and mother's breast cancer risk.
AB  - Pregnancy can both reduce and increase lifetime breast cancer risk, and it also
      induces a short-term, transient increase in risk. Several biological mechanisms
      have been proposed to explain the protective effect, including pregnancy-induced
      increase in circulating estrogen levels leading to reduced estrogen receptor (ER)
      expression and activity. Persistent changes in ER-regulated gene expression may
      then alter the response of the breast to postpregnancy hormonal exposures
      originating, for example, from food. Understanding how pregnancy increases breast
      cancer risk has received less attention. Human studies indicate that those women
      who were exposed to an elevated pregnancy estrogenic environment, such as women
      who took the synthetic estrogen diethylstilbestrol or who had the highest
      circulating estrogen levels at the beginning or end of pregnancy, are at
      increased risk of developing breast cancer. There is also evidence that elevated
      leptin levels, for example, in pregnant women who gained excessive amount of
      weight, increase later breast cancer risk. This may reflect a close interaction
      between estradiol (E2), ER, and leptin. Our preclinical study suggests that an
      exposure to excess pregnancy E2 and leptin levels reverses the protective changes
      in genomic signaling pathways seen in the breast/mammary gland of parous women
      and rodents. Recent findings indicate that involution - the period after
      lactation when the breast regresses back to prepregnancy stage - may be related
      to some pregnancy-associated breast cancers. Importantly, in a preclinical model,
      the increase can be reversed by anti-inflammatory treatment, offering hope that
      the increase in lifelong breast cancer risk induced by late first pregnancy or by
      an exposure of pregnant women to an excessive hormonal environment may be
      reversible. 

PMID- 25961352
TI  - Hormonal enzymatic systems in normal and cancerous human breast: control,
      prognostic factors, and clinical applications.
AB  - The bioformation and transformation of estrogens and other hormones in the breast
      tissue as a result of the activity of the various enzymes involved attract
      particular attention for the role they play in the development and pathogenesis
      of hormone-dependent breast cancer. The enzymatic process concerns the aromatase,
      which transforms androgens into estrogens; the sulfatase, which hydrolyzes the
      biologically inactive sulfates to the active hormone; the 17beta-hydroxysteroid
      dehydrogenases, which are involved in the interconversion estradiol/estrone or
      testosterone/androstenedione; hydroxylases, which transform estrogens into
      mitotic and antimitotic derivatives; and sulfotransferases and glucuronidases,
      which, respectively convert into the biologically inactive sulfates and
      glucuronides. These enzymatic activities are more intense in the carcinoma than
      in the normal tissue. Concerning aromatase, the application of antiaromatase
      agents has been largely developed in the treatment of breast cancer patients,
      with very positive results. Various studies have shown that the activity levels
      of these enzymes and their mRNA can be involved as interesting prognostic factors
      for breast cancer. In conclusion, the application of new antienzymatic molecules
      can open attractive perspectives in the treatment of hormone-dependent breast
      cancer. 

PMID- 25961353
TI  - Molecular mechanisms of oestrogen action on growth of human breast cancer cells
      in culture.
AB  - Growth responses to oestrogen can be reproducibly obtained using a selection of
      oestrogen-receptor-containing human breast cancer cell lines, and molecular
      mechanisms have been shown to include modulation to growth
      factor/receptor/signalling pathways, cell-cycle proteins, apoptosis,
      differentiation, adhesion, motility and migration. Considerable progress has been
      made in understanding the molecular basis of oestrogen action on gene expression
      through the ligand-activated transcription factors human oestrogen receptor alpha
      (ERalpha) and ERbeta and the resulting effects on global gene expression
      patterns, but the full profile of coordination of the alterations, which brings
      about changes in cell growth through genomic and non-genomic mechanisms remain to
      be fully elucidated. Oestrogen regulation of cell growth involves a complex cross
      talk between oestrogen receptor and growth factor signalling pathways such that
      inhibition of one pathway may lead to stimulation of another, which may explain
      the remarkable ability of human breast cancer cells to escape from any mode of
      imposed growth inhibition be it oestrogen deprivation or administration of
      antioestrogen. Although studies on cell growth have focused to date on the
      effects of physiological oestrogens, many hundreds of environmental chemicals
      with oestrogenic properties have now been measured in the human breast. Whether
      or not the weight of evidence eventually establishes any causal link of complex
      mixtures of environmental oestrogenic chemicals with breast cancer, the presence
      of so many oestrogenic chemicals in the breast must influence resulting
      oestrogenic responses, and the impact of this additional oestrogenic burden needs
      to be taken into account in future studies on growth regulation of human breast
      cancer cells. 

PMID- 25961354
TI  - Search for novel therapies for triple negative breast cancers (TNBC): analogs of
      luteinizing hormone-releasing hormone (LHRH) and growth hormone-releasing hormone
      (GHRH).
AB  - Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that
      is clinically negative for the expression of estrogen and progesterone receptors
      (ER/PR) and human epidermal growth factor receptor-2 (HER2). Patients with TNBC
      have a worse clinical outcome, as measured by time to metastasis and median
      overall survival. Chemotherapy has been the mainstay of treatment of TNBC but
      responses are disappointing. A substantial proportion of TNBC expresses
      luteinizing hormone-releasing hormone (LHRH), receptors for LHRH, in addition to
      receptors for growth hormone-releasing hormone (GHRH). These receptors represent
      potential therapeutic targets. Potent antagonists of GHRH and LHRH receptors have
      been developed in recent years and these antagonists inhibit the growth,
      tumorigenicity and metastatic potential of various human experimental
      malignancies. These antagonists could be utilized for the treatment of TNBC. The
      targeted cytotoxic analog of LHRH, AN-152 (AEZS-108) containing doxorubicin, must
      also be strongly considered for therapy of TNBC. Experimental studies suggest the
      merit of clinical trials with LHRH antagonists and AEZS-108 in TNBC patients. 

PMID- 25961355
TI  - Estetrol prevents and suppresses mammary tumors induced by DMBA in a rat model.
AB  - BACKGROUND: Estetrol (E4) is a pregnancy-specific estrogenic steroid hormone
      produced by the human fetal liver in both male and female fetuses. During
      pregnancy, E4 plasma values increase exponentially until parturition and decrease
      thereafter. The synthesis of E4 in the liver of a newborn ceases during the first
      weeks after birth. MATERIALS AND METHODS: Here we report the effect of E4 on the
      initiation and growth of mammary tumors chemically induced by 7,12
      dimethylbenz(a)anthracene (DMBA) in female Sprague-Dawley rats in two different
      protocols. Two prevention studies to test the effect on initiation and growth of
      induced tumors and one intervention study to test the effect on tumor growth were
      performed. In the prevention studies, the effect of oral doses of E4 over a dose
      range of 0.5-3.0 mg/kg was investigated. In the intervention study, oral doses of
      1, 3 and 10 mg/kg E4 were used. The anti-estrogen tamoxifen (TAM) and
      ethinylestradiol (EE) were used as reference compounds. In all studies, a group
      with ovariectomized animals (OVX) was included. RESULTS: In the prevention
      studies, 2.5 mg and 3 mg/kg E4 showed a significant effect on the number and
      growth of induced tumors by DMBA, and the effects were comparable to those of
      TAM, whereas EE had no effect. In the intervention study, the effect of a high
      dose of E4 (10 mg/kg) on tumor number was similar to that of OVX and better than
      TAM and high-dose EE. The 3 mg/kg E4 had an effect comparable to high-dose EE.
      The treatment effects were largely due to complete regression of existing tumors.
      CONCLUSIONS: The natural fetal estrogen E4 prevents tumor initiation by DMBA and
      inhibits the growth of existing DMBA-induced tumors.

PMID- 25961356
TI  - Recent Advances in High Altitude Medicine and Biology.

PMID- 25961357
TI  - Does testing impair relational processing? Failed attempts to replicate the
      negative testing effect.
AB  - Recent research on testing effects (i.e., practice tests are more effective than
      restudy for enhancing subsequent memory) has focused on explaining when and why
      testing enhances memory. Of particular interest for present purposes, Zaromb and
      Roediger (2010) reported evidence that testing effects in part reflect enhanced
      relational processing, which refers to the encoding of similarity among to-be
      learned items. The multifactor account of testing effects (Peterson & Mulligan,
      2013) further distinguishes between processing of cue-target relations (intraitem
      relational processing) and processing of relations shared by targets from
      different items (interitem relational processing). The intriguing claim of this
      account is that testing enhances intraitem relational processing at the expense
      of interitem relational processing. Confirming predictions of this account,
      Peterson and Mulligan (2013) found negative testing effects on final free recall
      and on a measure of interitem relational processing (the same measures on which
      Zaromb and Roediger found positive testing effects). The original intent of the
      current research was to resolve this theoretical debate by replicating and
      extending the findings of Peterson and Mulligan (2013) to identify the locus of
      the apparent inconsistency in the outcomes reported in these 2 studies. However,
      5 high-powered experiments affording 8 comparisons of testing versus restudy did
      not replicate the negative testing effect on final memory performance nor on most
      measures of interitem relational processing. Thus, the weight of the evidence
      supports the conclusion that testing does not impair relational processing.

PMID- 25961359
TI  - Sensitivity to morphological composition in spoken word recognition: Evidence
      from grammatical and lexical identification tasks.
AB  - Access to morphological structure during lexical processing has been established
      across a number of languages; however, it remains unclear which constituents are
      held as mental representations in the lexicon. The present study examined the
      auditory recognition of different noun types across 2 experiments. The critical
      manipulations were morphological complexity and the presence of a verbal
      derivation or nominalizing suffix form. Results showed that nominalizations, such
      as "explosion," were harder to classify as a noun but easier to classify as a
      word when compared with monomorphemic words with similar actionlike semantics,
      such as "avalanche." These findings support the claim that listeners decompose
      morphologically complex words into their constituent units during processing.
      More specifically, the results suggest that people hold representations of base
      morphemes in the lexicon.

PMID- 25961358
TI  - Subsequent to suppression: Downstream comprehension consequences of noun/verb
      ambiguity in natural reading.
AB  - We used eye tracking to investigate the downstream processing consequences of
      encountering noun/verb (NV) homographs (i.e., park) in semantically neutral but
      syntactically constraining contexts. Target words were followed by a
      prepositional phrase containing a noun that was plausible for only 1 meaning of
      the homograph. Replicating previous work, we found increased first fixation
      durations on NV homographs compared with unambiguous words, which persisted into
      the next sentence region. At the downstream noun, we found plausibility effects
      following ambiguous words that were correlated with the size of a reader's first
      fixation effect, suggesting that this effect reflects the recruitment of
      processing resources necessary to suppress the homograph's context-inappropriate
      meaning. Using these same stimuli, Lee and Federmeier (2012) found a sustained
      frontal negativity to the NV homographs, and, on the downstream noun, found a
      plausibility effect that was also positively correlated with the size of a
      reader's ambiguity effect. Together, these findings suggest that when only
      syntactic constraints are available, meaning selection recruits inhibitory
      mechanisms that can be measured in both first fixation slowdown and event-related
      potential ambiguity effects.

PMID- 25961360
TI  - How strongly linked are mental time and space along the left-right axis?
AB  - Different lines of research suggest that our mental representations of time and
      space are linked, though the strength of this linkage has only recently been
      addressed for the front-back mental timeline (Eikmeier, Schroter, Maienborn, Alex
      Ruf, & Ulrich, 2013). The present study extends this investigation to the left
      right mental timeline. In contrast to what was found in the cited previous study,
      the obtained space-time congruency effects were smaller than benchmark stimulus
      response congruency effects in control conditions. This pattern of results
      suggests that the representations of time and space are less strongly linked for
      the left-right axis than for the back-front axis.

PMID- 25961361
TI  - An exemplar-model account of feature inference from uncertain categorizations.
AB  - In a highly systematic literature, researchers have investigated the manner in
      which people make feature inferences in paradigms involving uncertain
      categorizations (e.g., Griffiths, Hayes, & Newell, 2012; Murphy & Ross, 1994,
      2007, 2010a). Although researchers have discussed the implications of the results
      for models of categorization and inference, an explicit formal model that
      accounts for the full gamut of results has not been evaluated. Building on
      previous proposals, in this theoretical note I consider the predictions from an
      exemplar model of categorization in which the inferred category label becomes a
      new feature of the objects. The model predicts a priori a wide range of robust
      results that have been documented in this literature and can also be used to
      interpret effects of experimental manipulations (PsycINFO Database Record

PMID- 25961362
TI  - Predicting Incongruence between Self-reported and Documented Colorectal Cancer
      Screening in a Sample of African American Medicare Recipients.
AB  - Assessments of colorectal cancer (CRC) screening rates typically rely on self
      reported screening data, which are often incongruent with medical records. We
      used multilevel models to examine health-related, socio-demographic and
      psychological predictors of incongruent self-reports for CRC screening among
      Medicare-insured African Americans (N = 3,740). Results indicated that living
      alone decreased, and income increased, the odds of congruently self-reporting
      endoscopic CRC screening. Being male and having greater number of comorbidities
      decreased, and having less than a high school education increased, the odds of
      congruently self-reported fecal occult blood tests. Living alone, age and income
      had the most robust effects across classifications into one of four mutually
      exclusive categories defined by screening status (screened/unscreened) and
      congruence of self-reports. The results underscore the clinical importance of
      gathering socio-demographic data via patient interviews, and the relevance of
      these data for judging the veracity of self-reported CRC screenings behaviors.

PMID- 25961363
TI  - Bioresorbable polyelectrolytes for smuggling drugs into cells.
AB  - There is ample evidence that biodegradable polyelectrolyte nanocapsules are
      multifunctional vehicles which can smuggle drugs into cells, and release them
      upon endogenous activation. A large number of endogenous stimuli have already
      been tested in vitro, and in vivo research is escalating. Thus, the interest in
      the design of intelligent polyelectrolyte multilayer (PEM) drug delivery systems
      is clear. The need of the hour is a systematic translation of PEM-based drug
      delivery systems from the lab to clinical studies. Reviews on multifarious
      stimuli that can trigger the release of drugs from such systems already exist.
      This review summarizes the available literature, with emphasis on the recent
      progress in PEM-based drug delivery systems that are receptive in the presence of
      endogenous stimuli, including enzymes, glucose, glutathione, pH, and temperature,
      and addresses different active and passive drug targeting strategies. Insights
      into the current knowledge on the diversified endogenous approaches and
      methodological challenges may bring inspiration to resolve issues that currently
      bottleneck the successful implementation of polyelectrolytes into the catalog of
      third-generation drug delivery systems. 

PMID- 25961364
TI  - Extraction of superoxide dismutase, catalase, and carbonic anhydrase from stroma
      free red blood cell hemolysate for the preparation of the nanobiotechnological
      complex of polyhemoglobin-superoxide dismutase-catalase-carbonic anhydrase.
AB  - We report a novel method to simultaneously extract superoxide dismutase (SOD),
      catalase (CAT), and carbonic anhydrase (CA) from the same sample of red blood
      cells (RBCs). This avoids the need to use expensive commercial enzymes, thus
      enabling a cost-effective process for large-scale production of a
      nanobiotechnological polyHb-SOD-CAT-CA complex, with enhancement of all three red
      blood cell functions. An optimal concentration of phosphate buffer for ethanol
      chloroform treatment results in good recovery of CAT, SOD, and CA after
      extraction. Different concentrations of the enzymes can be used to enhance the
      activity of polyHb-SOD-CAT-CA to 2, 4, or 6 times that of RBC. 

PMID- 25961366
TI  - Corrigendum.

PMID- 25961365
TI  - Advancement in recombinant protein production using a marine oxygen carrier to
      enhance oxygen transfer in a CHO-S cell line.
AB  - Recombinant proteins, particularly proteins used as therapeutics, are widely
      expressed for bioprocessing manufacturing processes. Mammalian cell lines
      represent the major host cells for bioproduction, according to their capacities
      of post-translational modifications and folding of secreted proteins. Many
      parameters can affect cell productivity, especially the rate of oxygen transfer.
      Dissolved oxygen, in high or low proportions, is a crucial parameter which can
      affect cell viability and thus productivity. HEMARINA has developed a new
      technology, commercially proposed as HEMOXCell((r)), to improve cell culture at a
      large production scale. HEMOXCell((r)) is a marine oxygen carrier having
      properties of high oxygen sensitivity, to be used as an oxygen additive during
      cell culture manufacturing. In this study, we investigated the effects of
      HEMOXCell((r)) on the culture of the commonly used CHO-S cell line. Two main
      objectives were pursued: 1) cell growth rate and viability during a batch mode
      process, and 2) the determination of the effect of this oxygen carrier on
      recombinant protein production from a CHO-transfected cell line. Our results show
      an increase of CHO-S cellular growth at a rate of more than four-fold in culture
      with HEMOXCell((r)). Moreover, an extension of the growth exponential phase and
      high cell viability were observed. All of these benefits seem to contribute to
      the improvement of recombinant protein production. This work underlines several
      applications using this marine-type oxygen carrier for large biomanufacturing. It
      is a promising cell culture additive according to the increasing demand for
      therapeutic products such as monoclonal antibodies. 

PMID- 25961367
TI  - A randomized controlled trial of a diagnostic algorithm for symptoms of
      uncomplicated cystitis at an out-of-hours service.
AB  - OBJECTIVE: To compare the clinical outcome of patients presenting with symptoms
      of uncomplicated cystitis who were seen by a doctor, with patients who were given
      treatment following a diagnostic algorithm. DESIGN: Randomized controlled trial.
      SETTING: Out-of-hours service, Oslo, Norway. INTERVENTION: Women with typical
      symptoms of uncomplicated cystitis were included in the trial in the time period
      September 2010-November 2011. They were randomized into two groups. One group
      received standard treatment according to the diagnostic algorithm, the other
      group received treatment after a regular consultation by a doctor. SUBJECTS:
      Women (n = 441) aged 16-55 years. Mean age in both groups 27 years. MAIN OUTCOME
      MEASURES: Number of days until symptomatic resolution. RESULTS: No significant
      differences were found between the groups in the basic patient demographics,
      severity of symptoms, or percentage of urine samples with single culture growth.
      A median of three days until symptomatic resolution was found in both groups. By
      day four 79% in the algorithm group and 72% in the regular consultation group
      were free of symptoms (p = 0.09). The number of patients who contacted a doctor
      again in the follow-up period and received alternative antibiotic treatment was
      insignificantly higher (p = 0.08) after regular consultation than after treatment
      according to the diagnostic algorithm. There were no cases of severe
      pyelonephritis or hospital admissions during the follow-up period. CONCLUSION:
      Using a diagnostic algorithm is a safe and efficient method for treating women
      with symptoms of uncomplicated cystitis at an out-of-hours service. This
      simplification of treatment strategy can lead to a more rational use of
      consultation time and a stricter adherence to National Antibiotic Guidelines for
      a common disorder.

PMID- 25961368
TI  - Antinociceptive and Anti-Inflammatory Activities of Telfairia occidentalis
      Hydroethanolic Leaf Extract (Cucurbitaceae).
AB  - Telfairia occidentalis (Cucurbitaceae) is a tropical vine grown in West Africa as
      a leaf vegetable and for its edible seeds. The plant is noted to have healing
      properties. It is used as a blood tonic to revive weak/ill individuals and its
      use by sickle cell patients has been documented. In this study, the
      antinociceptive activity of the hydroethanolic leaf extract of Telfairia
      occidentalis (TO) was evaluated using the acetic acid-induced writhing, formalin,
      tail clip, and hot plate tests in mice. The carrageenan- and egg albumin-induced
      rat paw edema tests were used to evaluate the anti-inflammatory action. The
      extract (50-400 mg/kg, p.o.) produced significant (P<.05) dose-dependent
      inhibition of pain response elicited by acetic acid and formalin while also
      increasing the nociceptive reaction latency in the tail clip and hot plate tests.
      In respect of anti-inflammatory activity, the extract elicited significant
      (P<.05) time and dose-dependent inhibition of edema development in the
      carrageenan and egg albumin tests. Peak effects of TO in the models were
      generally comparable with the effects of the standard drugs (acetylsalicylic
      acid, morphine, indomethacin, and chlorpheniramine) used. Phytochemical screening
      of the extract revealed the presence of tannins, saponins, phlobatannins, and
      anthraquinones. The extract did not produce any mortality and visible signs of
      delayed toxicity when administered orally up to 2000 mg/kg. The LD50 (i.p.) was
      estimated to be 4073.80 mg/kg. The results obtained in this study suggest that TO
      possesses antinociceptive and anti-inflammatory activities possibly mediated
      through peripheral and central mechanisms involving inhibition of release and/or
      actions of vasoactive substances and prostaglandins.

PMID- 25961370
TI  - Corrigendum.

PMID- 25961371
TI  - Impact of psychotherapist expectations on client outcomes.
AB  - Recent investigations have implicated client expectations of psychotherapy as a
      strong predictor of premature termination; however, there is reason to believe
      psychotherapist expectations may also impact client outcomes. This study sought
      to address this gap in the literature by examining the association of
      psychotherapists' expectations to clients' psychotherapy outcomes, including
      termination status. Participants were 54 current and recent trainee
      psychotherapists at a Southern public university, who completed delay discounting
      measures to assess their expectations of the effectiveness of psychotherapy. Data
      were also drawn from 300 adult clients who had received at least 2 sessions of
      individual psychotherapy from the participating psychotherapists of this study,
      and had previously completed the Outcome Questionnaire 45.2 prior to each
      individual therapy session. Psychotherapists were found to hold significantly
      higher expectations for client improvement than anticipated, based on existing
      literature, and these high expectations were found to be positively correlated
      with clinically significant change in clients. Moreover, psychotherapists'
      expectations were found to explain 7.3% of the explainable variance in whether or
      not clients experienced clinically significant change during psychotherapy.
      Implications for improving client retention and treatment outcome are discussed.

PMID- 25961369
TI  - Low miR-145 silenced by DNA methylation promotes NSCLC cell proliferation,
      migration and invasion by targeting mucin 1.
AB  - MiR-145 has been implicated in the progression of non-small cell lung cancer
      (NSCLC); however, its exact mechanism is not well established. Here, we report
      that miR-145 expression is decreased in NSCLC cell lines and tumor tissues and
      that this low level of expression is associated with DNA methylation. MiR-145
      methylation in NSCLC was correlated with a more aggressive tumor phenotype and
      was associated with poor survival time, as shown by Kaplan-Meier analysis.
      Additional multivariate Cox regression analysis indicated that miR-145
      methylation was an independent prognostic factor for poor survival in patients
      with NSCLC. Furthermore, we found that restoration of miR-145 expression
      inhibited proliferation, migration and invasion of NSCLC by the direct targeting
      of mucin 1 by miR-145. Our results indicate that low miR-145 expression, due to
      methylation, promotes NSCLC cell proliferation, migration and invasion by
      targeting mucin 1. Therefore, miR-145 may be a valuable therapeutic target for
      NSCLC. 

PMID- 25961372
TI  - WELLFOCUS PPT: Modifying positive psychotherapy for psychosis.
AB  - Positive psychotherapy (PPT) is an established psychological intervention
      initially validated with people experiencing symptoms of depression. PPT is a
      positive psychology intervention, an academic discipline that has developed
      somewhat separately from psychotherapy and focuses on amplifying well-being
      rather than ameliorating deficit. The processes targeted in PPT (e.g., strengths,
      forgiveness, gratitude, savoring) are not emphasized in traditional psychotherapy
      approaches to psychosis. The goal in modifying PPT is to develop a new clinical
      approach to helping people experiencing psychosis. An evidence-based theoretical
      framework was therefore used to modify 14-session standard PPT into a manualized
      intervention, called WELLFOCUS PPT, which aims to improve well-being for people
      with psychosis. Informed by a systematic review and qualitative research,
      modification was undertaken in 4 stages: qualitative study, expert consultation,
      manualization, and stake-holder review. The resulting WELLFOCUS PPT is a theory
      based 11-session manualized group therapy.

PMID- 25961373
TI  - The effects of cognitive behavioral therapy as an anti-depressive treatment is
      falling: A meta-analysis.
AB  - A meta-analysis examining temporal changes (time trends) in the effects of
      cognitive behavioral therapy (CBT) as a treatment for unipolar depression was
      conducted. A comprehensive search of psychotherapy trials yielded 70 eligible
      studies from 1977 to 2014. Effect sizes (ES) were quantified as Hedge's g based
      on the Beck Depression Inventory (BDI) and the Hamilton Rating Scale for
      Depression (HRSD). Rates of remission were also registered. The publication year
      of each study was examined as a linear metaregression predictor of ES, and as
      part of a 2-way interaction with other moderators (Year * Moderator). The average
      ES of the BDI was 1.58 (95% CI [1.43, 1.74]), and 1.69 for the HRSD (95% CI
      [1.48, 1.89]). Subgroup analyses revealed that women profited more from therapy
      than did men (p < .05). Experienced psychologists (g = 1.55) achieved better
      results (p < .01) than less experienced student therapists (g = 0.98). The
      metaregressions examining the temporal trends indicated that the effects of CBT
      have declined linearly and steadily since its introduction, as measured by
      patients' self-reports (the BDI, p < .001), clinicians' ratings (the HRSD, p <
      .01) and rates of remission (p < .01). Subgroup analyses confirmed that the
      declining trend was present in both within-group (pre/post) designs (p < .01) and
      controlled trial designs (p = .02). Thus, modern CBT clinical trials seemingly
      provided less relief from depressive symptoms as compared with the seminal
      trials. Potential causes and possible implications for future studies are
      discussed. (PsycINFO Database Record 

PMID- 25961374
TI  - Heritability of personality: A meta-analysis of behavior genetic studies.
AB  - The aim of this meta-analysis was to systematize available findings in the field
      of personality heritability and test for possible moderator effects of study
      design, type of personality model, and gender on heritability estimates. Study
      eligibility criteria were: personality model, behavior genetic study design, self
      reported data, essential statistical indicators, and independent samples. A total
      of 134 primary studies with 190 potentially independent effect sizes were
      identified. After exclusion of studies that did not meet inclusion criteria
      and/or met 1 of the exclusion criteria, the final sample included 62 independent
      effect sizes, representing more than 100,000 participants of both genders and all
      ages. Data analyses were performed using the random-effects model, software
      program R package metafor. The average effect size was .40, indicating that 40%
      of individual differences in personality were due to genetic, while 60% are due
      to environmental influences. After correction for possible publication bias the
      conclusion was unaltered. Additional analyses showed that personality model and
      gender were not significant moderators of personality heritability estimate,
      while study design was a significant moderator with twin studies showing higher
      estimates, .47, compared to family and adoption studies, .22. Personality model
      also was not a significant moderator of heritability estimates for neuroticism or
      extraversion, 2 personality traits contained in most personality trait theories
      and/or models. This study is the first to empirically test and confirm moderator
      effect of study design on heritability estimates in the field of personality.
      Limitations of the study, as well as suggestion for future studies, are
      discussed. (PsycINFO Database Record 

PMID- 25961375
TI  - Correction to Wen and Fan (2015).
AB  - Reports an error in "Monotonicity of Effect Sizes: Questioning Kappa-Squared as
      Mediation Effect Size Measure" by Zhonglin Wen and Xitao Fan (Psychological
      Methods, Advanced Online Publication, Feb 9, 2015, np). There were various errors
      pertaining to the use of variable "R". Under the heading Lack of Monotonicity of
      k2, the second, eleventh, and thirteenth paragraph and under the heading
      Paradoxical Behaviors of k2 Multiple Mediation Models, the third paragraph
      incorrectly italicized the variable "R." All versions of this article have been
      corrected. (The following abstract of the original article appeared in record
      2015-04977-001.) Mediation analysis is important for research in psychology and
      other social and behavioral sciences. Great progress has been made in testing
      mediation effects and in constructing their confidence intervals. Mediation
      effect sizes have also been considered. Preacher and Kelley (2011) proposed and
      recommended kappa2 as an effect size measure for a mediation effect. In this
      article, we argue that kappa2 is not an appropriate effect size measure for
      mediation models, because of its lack of the property of rank preservation (e.g.,
      the magnitude of kappa2 may decrease when the mediation effect that kappa2
      represents increases). Furthermore, kappa2 can lead to paradoxical results in
      multiple mediation models. We show that the problem of kappa2 is due to (a) the
      improper calculation of the maximum possible value of the indirect effect, and
      (b) mathematically, the maximum possible indirect effect is infinity, implying
      that the definition of kappa2 is mathematically incorrect. At this time, it
      appears that the traditional mediation effect size measure PM (the ratio of the
      indirect effect to the total effect), together with some other statistical
      information, should be preferred for basic mediation models. But for inconsistent
      mediation models where the indirect effect and the direct effect have opposite
      signs, the situation is less clear. Other considerations and suggestions for
      future research are also discussed.

PMID- 25961377
TI  - Resonance Raman Spectra of Five-Coordinate Heme-Nitrosyl Cytochromes c': Effect
      of the Proximal Heme-NO Environment.
AB  - Five-coordinate heme nitrosyl complexes (5cNO) underpin biological heme-NO signal
      transduction. Bacterial cytochromes c' are some of the few structurally
      characterized 5cNO proteins, exhibiting a distal to proximal 5cNO transition of
      relevance to NO sensing. Establishing how 5cNO coordination (distal vs proximal)
      depends on the heme environment is important for understanding this process.
      Recent 5cNO crystal structures of Alcaligenes xylosoxidans cytochrome c' (AXCP)
      and Shewanella frigidimarina cytochrome c' (SFCP) show a basic residue (Arg124
      and Lys126, respectively) near the proximal NO binding sites. Using resonance
      Raman (RR) spectroscopy, we show that structurally characterized 5cNO complexes
      of AXCP variants and SFCP exhibit a range of nu(NO) (1651-1671 cm(-1)) and
      nu(FeNO) (519-536 cm(-1)) vibrational frequencies, depending on the nature of the
      proximal heme pocket and the sample temperature. While the AXCP Arg124 residue
      appears to have little impact on 5cNO vibrations, the nu(NO) and nu(FeNO)
      frequencies of the R124K variant are consistent with (electrostatically) enhanced
      Fe(II) -> (NO)pi* backbonding. Notably, RR frequencies for SFCP and R124A AXCP
      are significantly displaced from the backbonding trendline, which in light of
      recent crystallographic data and density functional theory modeling may reflect
      changes in the Fe-N-O angle and/or extent of sigma-donation from the NO(pi*) to
      the Fe(II) (dz(2)) orbital. For R124A AXCP, correlation of vibrational and
      crystallographic data is complicated by distal and proximal 5cNO populations.
      Overall, this study highlights the complex structure-vibrational relationships of
      5cNO proteins that allow RR spectra to distinguish 5cNO coordination in certain
      electrostatic and steric environments. 

PMID- 25961376
TI  - Rational combination of MEK inhibitor and the STAT3 pathway modulator for the
      therapy in K-Ras mutated pancreatic and colon cancer cells.
AB  - K-Ras mutations are frequently detected in pancreatic and colon cancers, which
      are associated with the resistance to MEK inhibitors targeting the Ras pathway.
      Identifying the underlying mechanisms for the acquired resistance is essential
      for the future clinical development of MEK inhibitors. Here, we identified that
      Signal Transducer and Activator of Transcription 3 (STAT3) was significantly
      activated following the MEK inhibition using AZD6244, PD98059 and Trametinib in K
      Ras mutant pancreatic and colon cancer cells. The STAT3 activation may be
      important for the MEK inhibitor resistance in these K-Ras mutant cancer cells. We
      have shown that dual inhibition of STAT3 and MEK using the STAT3 inhibitor LY5
      and MEK inhibitor Trametinib exerts significant anti-tumor cell efficacy in K-Ras
      mutant pancreatic and colon cancer cells in vitro. In addition, Trametinib showed
      increased suppression on tumor growth in vivo in STAT3 knockdown pancreatic
      cancer cells compared with tumor growth of control cells without STAT3 knockdown.
      Taken together, our results suggest the induced STAT3 activation as a possible
      mechanism for the resistance to MEK inhibitor and demonstrate the potentials of a
      combination therapy using MEK and STAT3 inhibitors in pancreatic and colon
      cancers harboring K-Ras mutant proteins. 

PMID- 25961378
TI  - Core Lung Biopsy for Biomarker Analysis: Is There Increased Risk Compared With
      Conventional Biopsy?
AB  - PURPOSE: The aim of the study was to compare the rate of pneumothorax and chest
      tube placement in patients undergoing conventional lung biopsy with those
      undergoing core lung biopsy for biomarker analysis. MATERIALS AND METHODS: Twenty
      three patients had biopsies performed for biomarker analysis (5 male, 18 female
      patients, mean age 67 y), and 173 patients underwent standard diagnostic lung
      biopsy (86 male, 87 female patients, mean age 68 y). All biopsies were performed
      under computed tomography guidance using the coaxial technique (19 G introducer
      needle and 20 G core biopsy needle). The number of core samples was noted for
      each case, and all complications were recorded in accordance with Society of
      Interventional Radiology guidelines. RESULTS: In the biomarker analysis group, a
      mean of 5.1 core samples (range, 1 to 10) was obtained. In the conventional
      biopsy group, a mean of 2.9 core samples (range, 1 to 6) was obtained. The
      pneumothorax rate was 37.6% in the conventional biopsy group and 30.4% in the
      biomarker analysis group (P=0.505). The rate of chest tube placement was 16.8% in
      the conventional biopsy group and 8.7% in the biomarker analysis group (P=0.319).
      Lesion size was found to be an independent predictor of pneumothorax (P=0.031),
      whereas biopsy tract length was found to be an independent predictor of both
      pneumothorax (P<0.001) and chest tube placement (P=0.005) upon multivariate
      analysis. CONCLUSIONS: There is no statistically significant difference in the
      incidence of pneumothorax or chest tube placement between patients undergoing
      standard diagnostic lung biopsy and those requiring increased core samples for
      biomarker analysis.

PMID- 25961380
TI  - Toward Realization of 2.4 GHz Balunless Narrowband Receiver Front-End for Short
      Range Wireless Applications.
AB  - The demand for radio frequency (RF) transceivers operating at 2.4 GHz band has
      attracted considerable research interest due to the advancement in short range
      wireless technologies. The performance of RF transceivers depends heavily on the
      transmitter and receiver front-ends. The receiver front-end is comprised of a low
      noise amplifier (LNA) and a downconversion mixer. There are very few designs that
      focus on connecting the single-ended output LNA to a double-balanced mixer
      without the use of on-chip transformer, also known as a balun. The objective of
      designing such a receiver front-end is to achieve high integration and low power
      consumption. To meet these requirements, we present the design of fully
      integrated 2.4 GHz receiver front-end, consisting of a narrow-band LNA and a
      double balanced mixer without using a balun. Here, the single-ended RF output
      signal of the LNA is translated into differential signal using an NMOS-PMOS (n
      channel metal-oxide-semiconductor, p-channel metal-oxide-semiconductor)
      transistor differential pair instead of the conventional NMOS-NMOS transistor
      configuration, for the RF amplification stage of the double-balanced mixer. The
      proposed receiver circuit fabricated using TSMC 0.18 um CMOS technology operates
      at 2.4 GHz and produces an output signal at 300 MHz. The fabricated receiver
      achieves a gain of 16.3 dB and consumes only 6.74 mW operating at 1.5 V, while
      utilizing 2.08 mm2 of chip area. Measurement results demonstrate the
      effectiveness and suitability of the proposed receiver for short-range wireless
      applications, such as in wireless sensor network (WSN). 

PMID- 25961379
TI  - Highly Cost-Effective Nitrogen-Doped Porous Coconut Shell-Based CO2 Sorbent
      Synthesized by Combining Ammoxidation with KOH Activation.
AB  - The objective of this research is to develop a cost-effective carbonaceous CO2
      sorbent. Highly nanoporous N-doped carbons were synthesized with coconut shell by
      combining ammoxidation with KOH activation. The resultant carbons have
      characteristics of highly developed porosities and large nitrogen loadings. The
      prepared carbons exhibit high CO2 adsorption capacities of 3.44-4.26 and 4.77
      6.52 mmol/g at 25 and 0  degrees C under atmospheric pressure, respectively.
      Specifically, the sample NC-650-1 prepared under very mild conditions (650 
      degrees C and KOH/precursor ratio of 1) shows the CO2 uptake 4.26 mmol/g at 25 
      degrees C, which is among the best of the known nitrogen-doped porous carbons.
      The high CO2 capture capacity of the sorbent can be attributed to its high
      microporosity and nitrogen content. In addition, the CO2/N2 selectivity of the
      sorbent is as high as 29, higher than that of many reported CO2 sorbents.
      Finally, this N-doped carbon exhibits CO2 heats of adsorption as high as 42
      kJ/mol. The multiple advantages of these cost-effective coconut shell-based
      carbons demonstrate that they are excellent candidates for CO2 capture. 

PMID- 25961381
TI  - POIS, a Low Cost Tilt and Position Sensor: Design and First Tests.
AB  - An integrated sensor for the measurement and monitoring of position and
      inclination, characterized by low cost, small size and low weight, has been
      designed, realized and calibrated at the Geomatics Lab of the University of
      Calabria. The design of the prototype, devoted to the monitoring of landslides
      and structures, was aiming at realizing a fully automated monitoring instrument,
      able to send the data acquired periodically or upon request by a control center
      through a bidirectional transmission protocol. The sensor can be released with
      different accuracy and range of measurement, by choosing bubble vials with
      different characteristics. The instrument is provided with a computer, which can
      be programmed so as to independently perform the processing of the data collected
      by a single sensor or a by a sensor network, and to transmit, consequently, alert
      signals if the thresholds determined by the monitoring center are exceeded. The
      bidirectional transmission also allows the users to vary the set of the
      monitoring parameters (time of acquisition, duration of satellite acquisitions,
      thresholds for the observed data). In the paper, hardware and software of the
      sensor are described, along with the calibration, the results of laboratory tests
      and of the first in field acquisitions. 

PMID- 25961382
TI  - A Fuzzy-Based Fusion Method of Multimodal Sensor-Based Measurements for the
      Quantitative Evaluation of Eye Fatigue on 3D Displays.
AB  - With the rapid increase of 3-dimensional (3D) content, considerable research
      related to the 3D human factor has been undertaken for quantitatively evaluating
      visual discomfort, including eye fatigue and dizziness, caused by viewing 3D
      content. Various modalities such as electroencephalograms (EEGs), biomedical
      signals, and eye responses have been investigated. However, the majority of the
      previous research has analyzed each modality separately to measure user eye
      fatigue. This cannot guarantee the credibility of the resulting eye fatigue
      evaluations. Therefore, we propose a new method for quantitatively evaluating eye
      fatigue related to 3D content by combining multimodal measurements. This research
      is novel for the following four reasons: first, for the evaluation of eye fatigue
      with high credibility on 3D displays, a fuzzy-based fusion method (FBFM) is
      proposed based on the multimodalities of EEG signals, eye blinking rate (BR),
      facial temperature (FT), and subjective evaluation (SE); second, to measure a
      more accurate variation of eye fatigue (before and after watching a 3D display),
      we obtain the quality scores of EEG signals, eye BR, FT and SE; third, for
      combining the values of the four modalities we obtain the optimal weights of the
      EEG signals BR, FT and SE using a fuzzy system based on quality scores; fourth,
      the quantitative level of the variation of eye fatigue is finally obtained using
      the weighted sum of the values measured by the four modalities. Experimental
      results confirm that the effectiveness of the proposed FBFM is greater than other
      conventional multimodal measurements. Moreover, the credibility of the variations
      of the eye fatigue using the FBFM before and after watching the 3D display is
      proven using a t-test and descriptive statistical analysis using effect size. 

PMID- 25961383
TI  - A micro-computed tomography technique to study the quality of fibre optics
      embedded in composite materials.
AB  - Quality of embedment of optical fibre sensors in carbon fibre-reinforced polymers
      plays an important role in the resultant properties of the composite, as well as
      for the correct monitoring of the structure. Therefore, availability of a tool
      able to check the optical fibre sensor-composite interaction becomes essential.
      High-resolution 3D X-ray Micro-Computed Tomography, or Micro-CT, is a relatively
      new non-destructive inspection technique which enables investigations of the
      internal structure of a sample without actually compromising its integrity. In
      this work the feasibility of inspecting the position, the orientation and, more
      generally, the quality of the embedment of an optical fibre sensor in a carbon
      fibre reinforced laminate at unit cell level have been proven. 

PMID- 25961384
TI  - Quaternion-based unscented Kalman filter for accurate indoor heading estimation
      using wearable multi-sensor system.
AB  - Inertial navigation based on micro-electromechanical system (MEMS) inertial
      measurement units (IMUs) has attracted numerous researchers due to its high
      reliability and independence. The heading estimation, as one of the most
      important parts of inertial navigation, has been a research focus in this field.
      Heading estimation using magnetometers is perturbed by magnetic disturbances,
      such as indoor concrete structures and electronic equipment. The MEMS gyroscope
      is also used for heading estimation. However, the accuracy of gyroscope is
      unreliable with time. In this paper, a wearable multi-sensor system has been
      designed to obtain the high-accuracy indoor heading estimation, according to a
      quaternion-based unscented Kalman filter (UKF) algorithm. The proposed multi
      sensor system including one three-axis accelerometer, three single-axis
      gyroscopes, one three-axis magnetometer and one microprocessor minimizes the size
      and cost. The wearable multi-sensor system was fixed on waist of pedestrian and
      the quadrotor unmanned aerial vehicle (UAV) for heading estimation experiments in
      our college building. The results show that the mean heading estimation errors
      are less 10 degrees  and 5 degrees  to multi-sensor system fixed on waist of
      pedestrian and the quadrotor UAV, respectively, compared to the reference path. 

PMID- 25961385
TI  - Local allergic rhinitis: mechanisms, diagnosis and relevance for occupational
      rhinitis.
AB  - PURPOSE OF REVIEW: Local allergic rhinitis (LAR) is a new form of allergic
      rhinitis that has caused a growing interest. The possibility of an occupational
      equivalent (occupational rhinitis) has not been yet explored. The purpose of this
      review is to summarize the most relevant and recent scientific evidence on LAR
      and occupational rhinitis. RECENT FINDINGS: LAR is a prevalent entity well
      differentiated from allergic rhinitis, affecting patients from different
      countries, ethnic groups and ages. Occupational rhinitis appears earlier and more
      frequently than occupational asthma, especially for high molecular weight
      substances. Diagnosis of LAR is based on nasal allergen provocation test and/or
      detection of nasal specific IgE, and other techniques such as basophil activation
      test may support the diagnosis. Skin prick tests and immunological determinations
      are of limited use for diagnosis of occupational rhinitis caused by low molecular
      weight agents. Performance of nasal allergen provocation test for confirming
      diagnosis of occupational rhinitis is strongly recommended. Uncommon allergens
      should also be investigated. SUMMARY: The possibility of a local occupational
      rhinitis should be considered in workers with a clear history of occupational
      rhinitis and negative immunological test, especially in the case of high
      molecular weight allergens.

PMID- 25961386
TI  - New causes of immunologic occupational asthma, 2012-2014.
AB  - PURPOSE OF REVIEW: The objective of this study was to review all new causes of
      well documented immunologic occupational asthma (IOA) published in the English
      and French medical literature between January 2012 and mid-2014. RECENT FINDINGS:
      Ten case reports of new causes of IOA were reported during that period. The
      diagnosis was either confirmed by specific inhalation challenges (n = 5) or a
      combination of peak expiratory flow monitoring at and off work, confirmation of
      specific sensitisation, and asthma (n = 3). These involved both high (mites
      contaminating cured ham, various enzymes used as detergents and food additives,
      aquarium fish food, and orange allergens) and low-molecular-weight agents (spruce
      wood dust, a biocide, and an halogenated platinum compound used in cytotoxic
      drugs). Furthermore, eight studies reported cases of IOA with agents already
      known as airway sensitizers but in working environments that were unusual and
      reported for the first time. SUMMARY: There are more than 400 known causes of IOA
      and the list grows continuously with the development of new technologies and
      better recognition of the diagnosis by physicians. IgE-mediated sensitization was
      confirmed in all new cases involving high-molecular-weight agents and in two of
      the three new cases involving low-molecular-weight agents. Symptoms of rhinitis
      were often associated with both types of agents. Physicians should stay alert and
      suspect occupational asthma in any adult with new-onset asthma or with newly
      uncontrolled asthma.

PMID- 25961387
TI  - Longitudinal assessment of lung function decline in the occupational setting.
AB  - PURPOSE OF REVIEW: Spirometry is performed in the work setting as part of medical
      surveillance of workers with potentially respiratory hazardous work exposures, to
      identify early disease and evaluate the effectiveness of preventive
      interventions. However, many clinicians are not familiar with workplace medical
      surveillance and how to evaluate longitudinal spirometry over time. RECENT
      FINDINGS: A recent American Thoracic Society technical standards report addressed
      issues related to performing spirometry in the work setting, including the
      interpretation of longitudinal lung function. Important considerations in
      assessing longitudinal lung function are reviewed. Recent studies evaluating the
      impact of selected occupational exposures on longitudinal lung function are
      reviewed. SUMMARY: Recent longitudinal studies of exposed workers have identified
      novel occupational respiratory diseases such as flavoring-related lung disease,
      and advanced our understanding of more familiar exposures such as mineral dusts.
      Clinicians will increasingly need to be able to evaluate longitudinal spirometry,
      including thresholds that trigger further evaluation.

PMID- 25961388
TI  - Work-associated irritable larynx syndrome.
AB  - PURPOSE OF REVIEW: The purpose of this study is to review the relevant literature
      concerning work-associated irritable larynx syndrome (WILS), a hyperkinetic
      laryngeal disorder associated with occupational irritant exposure. Clinical
      symptoms are variable and include dysphonia, cough, dyspnoea and globus
      pharyngeus. WILS is a clinical diagnosis and can be difficult to differentiate
      from asthma. Treatment options for WILS include medical and behavioural therapy.
      RECENT FINDINGS: Laryngeal-centred upper airway symptoms secondary to airborne
      irritants have been documented in the literature under a variety of diagnostic
      labels, including WILS, vocal cord dysfunction (VCD), laryngeal hypersensitivity
      and laryngeal neuropathy and many others. The underlying pathophysiology is as
      yet poorly understood; however, the clinical scenario suggests a multifactorial
      nature to the disorder. More recent literature indicates that central neuronal
      plasticity, inflammatory processes and psychological factors are all likely
      contributors. SUMMARY: Possible mechanisms for WILS include central neuronal
      network plasticity after noxious exposure and/or viral infection, inflammation
      (i.e. reflux disease) and intrinsic patient factors such a psychological state.
      Treatment is individualized and frequently includes one or more of the following:
      environmental changes in the workplace, GERD therapy, behavioural/speech therapy,
      psychotherapy counselling and neural modifiers.

PMID- 25961389
TI  - Role of microRNAs in allergic asthma: present and future.
AB  - PURPOSE OF REVIEW: MicroRNAs (miRNAs) modulate gene transcription in response to
      environmental stressors and other stimuli. A role for miRNAs in inflammation and
      immunity has been demonstrated and further evidence suggests that miRNAs also
      play a role in allergic asthma. RECENT FINDINGS: Studies investigating the
      differential expression of miRNAs in biological fluids between asthma patients
      and controls have been published, as have their role in immune cell subsets.
      Further development of miRNAs in therapy has been addressed. miRNA-146a has been
      implicated in autoimmunity and allergic inflammation and miRNA-155 in the
      development of atopy. Targeting of miRNA-1 and miRNA-145 has been used to inhibit
      lung inflammation in mouse models of asthma. Although these recent findings need
      to be confirmed, miRNAs may prove to be useful as potential biomarkers of
      disease. However, their use as therapeutic targets in the lung remains unclear.
      SUMMARY: There may be a potential role for using circulating miRNAs as biomarkers
      of disease status or response to therapy. The use of miRNAs as asthma therapy
      remains to be determined.

PMID- 25961390
TI  - Airway molecular endotypes of asthma: dissecting the heterogeneity.
AB  - PURPOSE OF REVIEW: This review will cover advances over the past year in defining
      airway endotypes in asthma by gene expression and the relationship between these
      endotypes and clinical traits. RECENT FINDINGS: Expression profiling studies of
      asthmatic airway samples continue to reveal significant heterogeneity in airway
      inflammation and dysfunction. Recent studies have indicated multiple distinct,
      but related Th2 inflammatory asthma endotypes. Moreover, novel biomarkers of Th2
      inflammation are being identified in more accessible nasal brushing and induced
      sputum cell samples. New data suggest the presence of multiple non-Th2-driven
      asthma molecular endotypes, including ones related to neutrophilic inflammation,
      airway remodeling, and chemosensory dysfunction. Many of these endotypes are
      associated with clinical disease features and treatment response. SUMMARY:
      Molecular endotyping of asthmatic patients using gene expression profiling of
      airway samples is helping to uncover disease mechanisms and potential novel
      treatment targets. The advancement of endotyping methods holds the promise of
      future personalized treatment for asthma.

PMID- 25961391
TI  - Childhood asthma and chronic obstructive pulmonary disease: outcomes until the
      age of 50.
AB  - PURPOSE OF REVIEW: There has been recent interest in understanding the origins of
      chronic obstructive pulmonary disease. Epidemiological studies suggest that
      chronic obstructive pulmonary disease clearly has other causes apart from tobacco
      smoke. RECENT FINDINGS: Cross-sectional studies of adult cohorts with chronic
      obstructive pulmonary disease highlight that childhood asthma is a risk factor. A
      recent longitudinal childhood cohort study of children from childhood to the age
      of 50 years describes that children with severe asthma are at increased risk of
      chronic obstructive pulmonary disease and that the deficit in lung function can
      be tracked back to early years. SUMMARY: Children with severe asthma are at
      increased risk of developing chronic obstructive pulmonary disease.

PMID- 25961392
TI  - Early treatment in preschool children: an evidence-based approach.
AB  - PURPOSE OF REVIEW: Wheezing is a common symptom in early childhood but only some
      of these children will experience continued wheezing symptoms in later childhood
      making the diagnosis and treatment of these children challenging. This review
      covers recent findings regarding the epidemiology, diagnosis, evaluation, and
      treatment of preschool-aged children with asthma. RECENT FINDINGS: Key
      characteristics that distinguish the childhood asthma-predictive phenotype
      include male sex, history of wheezing with lower respiratory tract infections,
      history of parental asthma, history of atopic dermatitis, eosinophilia, early
      sensitization to food or aeroallergens, or lower lung function in early life. The
      preschool-aged asthma population tends to be characterized as exacerbation prone
      with relatively limited impairment. The diagnosis of asthma in preschool-aged
      children is often based on symptom patterns, presence of risk factors, and
      therapeutic responses. Asthma management includes intermittent and daily inhaled
      corticosteroids, daily leukotriene-receptor antagonists, and, in rare cases,
      combination therapies. SUMMARY: The diagnosis of asthma in preschool-aged
      children is based on symptom patterns and the presence of risk factors, and the
      goals of asthma management are achieved through a partnership between the family
      and the healthcare team using regular assessment of symptom control and response
      to daily controller therapy.

PMID- 25961393
TI  - Asthma, allergy and the Olympics: a 12-year survey in elite athletes.
AB  - OBJECTIVE: There are no comprehensive surveys relating the reported high
      prevalence of asthma and allergic diseases in athletes to comorbidities and
      immune changes associated with intense chronic exercise. This 12-year survey aims
      to evaluate several clinical, functional and immunological parameters in order to
      assess features, trend and burden of asthma, allergy, infections and autoimmune
      diseases, in a large homogeneous population of Olympic athletes. METHODS: Six
      hundred and fifty-nine Italian Olympic athletes were studied through four cross
      sectional surveys performed between 2000 and 2012 before the Summer and Winter
      Olympics. Clinical diagnosis of allergic, autoimmune and infectious diseases was
      complemented by: skin-prick tests (n = 569); pulmonary function tests (n = 415);
      total (n = 158) and specific (n = 72) serum IgE; serum autoantibodies (n = 30),
      cytokines and growth factors (n = 92); flow cytometry (n = 135). RESULTS: The
      prevalence of asthma and/or exercise-induced bronchoconstriction was 14.7%, with
      a significant increase (P = 0.04) from 2000 (11.3%) to 2008 (17.2%). The
      prevalence of rhinitis, conjunctivitis, skin allergic diseases and anaphylaxis
      was 26.2%, 20.0%, 14.8% and 1.1%, respectively. Sensitization to inhalant
      allergens was documented in 49.0% of athletes, being 32.7% in 2000 and 56.5% in
      2008 (P < 0.0001). Food, drug and venom allergy was present in 7.1%, 5.0% and
      2.1% of athletes, respectively. The high prevalence of asthma and allergy was
      associated with recurrent upper respiratory tract (10.3%) and herpes (18.2%)
      infections, an abnormal T cell subset profile and a general down-regulation of
      serum cytokines with a significantly lower IFN-gamma/IL-4 ratio. CONCLUSION: A
      chronic and intense physical exercise may cause a transient immunodepression with
      a preferential shift to a Th2 response, associated with abnormalities of the
      respiratory tract.

PMID- 25961395
TI  - Underestimation of the True Specificity of the Urine Lipoarabinomannan Point-of
      Care Diagnostic Assay for HIV-Associated Tuberculosis.

PMID- 25961396
TI  - Protein-Protein and Peptide-Protein Interactions of NudE-Like 1 (Ndel1): A
      Protein Involved in Schizophrenia.
AB  - Schizophrenia (SCZ) is a devastating chronic mental disease determined by genetic
      and environmental factors, which susceptibility may involve an impaired neural
      migration during the neurodevelopmental process. Several candidate risk genes
      potentially associated with SCZ were related to the formation of protein
      complexes that ultimately mediate alterations in the neuroplasticity. The most
      studied SCZ risk gene is the Disrupted-in-Schizophrenia 1 (DISC1) gene, which
      functions seem to depend on the binding with cytoskeleton proteins, as the
      Nuclear-distribution gene E homolog like-1 (Ndel1) protein among others.
      Interestingly, Ndel1 is the only binding partner of DISC1 proteins with
      oligopeptidase activity, besides playing roles in multiple processes, including
      cytoskeletal organization, cell signaling, neuron migration, and neurite
      outgrowth. It is still not clear if the protein-protein interaction between Ndel1
      and DISC1 is enough to explain all cellular functions attributed to these
      proteins, but there are several lines of evidence suggesting the importance of
      the catalytic activity of Ndel1 for the neurite outgrowth and neuron migration
      during embryogenesis. Recent works of the group have demonstrated the modulation
      of Ndel1 activity by DISC1, which is hypothetically impaired in SCZ patients. In
      fact, more recently, we also showed a lower Ndel1 activity in the plasma of SCZ
      patients compared to control health subjects, but the physiopathological
      significance of this feature is still unknown. Here we discuss Ndel1 ligands
      involved in protein-protein complex formations related to neurodevelopmental
      diseases, as (1) lissencephaly or Miller-Dieker Syndrome (MDS), which is
      characterized by the typical craniofacial features and abnormal smooth cerebral
      surface, and as (2) SCZ, since they both seem to be determined by defects in
      neuronal migration. Although impaired lissencephaly protein Lis1 complex
      formation with Ndel1 is the leading cause of lissencephaly, this binding does not
      affect Ndel1 oligopeptidase activity. On the other hand, although MDS and SCZ may
      be both determined by an abnormal neuronal migration, DISC1 complex formation
      with Ndel1 was shown to inhibit Ndel1 activity. Also differently of MDS, SCZ
      needs inputs from environmental factors, while lissencephaly is not likely
      dependent or affected by the environment. Several other proteins and peptide
      ligands were described for Ndel1, Lis1 and DISC1, thanks to the employment of
      biochemical, immunochemical, and biological (using cells or living animals)
      assays, including heterologous expression and also simply by purification from
      nature of these proteins in the complex form. Effects of the post-translational
      modifications of these proteins are also discussed here. Taken together, the data
      presented here show in essence how protein-protein and proteinpeptide
      interactions can underlie fundamental processes as cell division, maturation and
      migration, necessary for adequate formation of a complex structured tissue as the
      brain. A special attention was given to Ndel1 as this protein binds to either
      proteins or peptides, besides having proteolytic activity. Moreover, Ndel1 seems
      to be the key protein underlying two seemingly unrelated diseases with highly
      complex etiology, as lissencephaly and SCZ. 

PMID- 25961397
TI  - From Conformation to Interaction: Techniques to Explore the Hsp70/Hsp90 Network.
AB  - Proteins participate in almost every cell physiological function, and to do so,
      they need to reach a state that allows its function by folding and/or exposing
      surfaces of interactions. Spontaneous folding in the cell is in general hindered
      by its crowded and viscous environment, which favors misfolding and nonspecific
      and deleterious self-interactions. To overcome this, cells have a system, in
      which Hsp70 and Hsp90 play a central role to aid protein folding and avoid
      misfolding. The topics of this review include the biophysical tools used for
      monitoring protein-ligand and protein-protein interactions and also some
      important results related to the study of molecular chaperones and heat shock
      proteins (Hsp), with a focus on the Hsp70/Hsp90 network. The biophysical tools
      and their use to probe the conformation and interaction of Hsp70 and Hsp90 are
      briefly reviewed. 

PMID- 25961398
TI  - Using QCM and SPR for the Kinetic Evaluation of the Binding Between A New
      Recombinant Chimeric Protein and Specific Antibodies of the Visceral
      Leishmaniasis.
AB  - In the present study, the surface plasmon resonance (SPR) and quartz crystal
      microbalance (QCM) techniques were employed to kinetically evaluate the binding
      affinity of a new recombinant chimeric protein (CP10) toward anti-Leishmania
      infantum antibodies for the immunodiagnostics of the visceral leishmaniasis (VL).
      This chimeric protein was formed by the union in a same artificial coding DNA of
      ten different peptides, which showed themselves reactive toward positive canine
      serum for VL. Using the CP10 in enzyme-linked immunosorbent assays (ELISA), it
      was possible to detect 80% of the asymptomatic infected dogs. After this, SPR and
      QCM immunosensors were constructed by the covalent immobilization of the CP10 on
      a self-assembled monolayer (SAM) formed by adsorption of alkanethiol on gold
      substrates. The thickness (6.80 nm) and the refractive index (1.475) of the
      protein on the SAM were simultaneously determined through SPR curves measured in
      different wavelengths (670 and 785 nm). Interactions between the CP10 and its
      specific IgGs (anti-CP10 antibodies) were characterized by the electrochemical
      impedance spectroscopy, SPR and QCM techniques. The equilibrium dissociation
      constant obtained by SPR (K(D) = 8.27 x 10(-10) mol.L(-1)) and QCM (K(D) = 2.42 x
      10(- 10) mol.L(-1)) demonstrated high binding affinity of the CP10 toward anti
      CP10 antibodies. In this sense, this work quantitatively proves the strong
      antigenic character of a new recombinant chimeric protein, giving evidence to
      potential contribution for the use of this protein in programs of control of the
      VL.

PMID- 25961399
TI  - Biophysical Characterisation and Quantification of Nucleic Acid-Protein
      Interactions: EMSA, MST and SPR.
AB  - Cell viability is only possible due to a dynamic range of essential nucleic acid
      protein complex formation. DNA replication and repair, gene expression,
      transcription and protein synthesis are well-known processes mediated by nucleic
      acids (DNA and RNA) - protein interactions. Novel nucleic acid- protein complexes
      have been identified in the past few years aided by the development of numerous
      new techniques such as RNA capture or Tandem RNA Affinity Purification (TRAP).
      However, the biophysical and biochemical details of these interactions are mostly
      unknown. Here, we present three techniques (Electrophoretic Mobility Shift
      Assays, Microscale Thermophoresis and Surface Plasmon Resonance) that are
      commonly used to quantify and characterize DNA-protein and RNA-protein
      interactions and discuss their main advantages and limitations. 

PMID- 25961400
TI  - DNA Binding Proteins and Drug Delivery Vehicles: Tales of Elephants and Snakes.
AB  - We compare the DNA-interactive properties of bacteriophage T4 gene 32 protein
      (gp32) with those of crotamine, a component of the venom of the South American
      rattlesnake. Gene 32 protein is a classical single-stranded DNA binding protein
      that has served as a model for this class of proteins. We discuss its biological
      functions, structure, binding specificities, and how it controls its own
      expression. In addition, we delineate the roles of the structural domains of gp32
      and how they regulate the protein's various activities. Crotamine, a component of
      the venom of the South American rattlesnake, is probably not a DNA binding
      protein in nature, but clearly shows significant DNA binding in vitro. Crotamine
      has been shown to selectively disrupt rapidly dividing cells and this specificity
      has been demonstrated for crotamine-facilitated delivery of plasmid DNA Thus,
      crotamine, or a variant of the protein, could have important clinical and/or
      diagnostic roles. Understanding its DNA binding properties may therefore lead to
      more effective drug delivery vehicles. 

PMID- 25961401
TI  - Structural Insights into Substrate Binding of Brown Spider Venom Class II
      Phospholipases D.
AB  - Phospholipases D (PLDs), the major dermonecrotic factors from brown spider
      venoms, trigger a range of biological reactions both in vitro and in vivo.
      Despite their clinical relevance in loxoscelism, structural data is restricted to
      the apo-form of these enzymes, which has been instrumental in understanding the
      functional differences between the class I and II spider PLDs. The crystal
      structures of the native class II PLD from Loxosceles intermedia complexed with
      myo-inositol 1-phosphate and the inactive mutant H12A complexed with fatty acids
      indicate the existence of a strong ligand-dependent conformation change of the
      highly conserved aromatic residues, Tyr 223 and Trp225 indicating their roles in
      substrate binding. These results provided insights into the structural
      determinants for substrate recognition and binding by class II PLDs. 

PMID- 25961402
TI  - Computational Biology Tools for Identifying Specific Ligand Binding Residues for
      Novel Agrochemical and Drug Design.
AB  - The term "agrochemicals" is used in its generic form to represent a spectrum of
      pesticides, such as insecticides, fungicides or bactericides. They contain active
      components designed for optimized pest management and control, therefore allowing
      for economically sound and labor efficient agricultural production. A "drug" on
      the other side is a term that is used for compounds designed for controlling
      human diseases. Although drugs are subjected to much more severe testing and
      regulation procedures before reaching the market, they might contain exactly the
      same active ingredient as certain agrochemicals, what is the case described in
      present work, showing how a small chemical compound might be used to control
      pathogenicity of Gram negative bacteria Xylella fastidiosa which devastates
      citrus plantations, as well as for control of, for example, meningitis in humans.
      It is also clear that so far the production of new agrochemicals is not
      benefiting as much from the in silico new chemical compound
      identification/discovery as pharmaceutical production. Rational drug design
      crucially depends on detailed knowledge of structural information about the
      receptor (target protein) and the ligand (drug/agrochemical). The interaction
      between the two molecules is the subject of analysis that aims to understand
      relationship between structure and function, mainly deciphering some fundamental
      elements of the nanoenvironment where the interaction occurs. In this work we
      will emphasize the role of understanding nanoenvironmental factors that guide
      recognition and interaction of target protein and its function modifier, an
      agrochemical or a drug. The repertoire of nanoenvironment descriptors is used for
      two selected and specific cases we have approached in order to offer a
      technological solution for some very important problems that needs special
      attention in agriculture: elimination of pathogenicity of a bacterium which is
      attacking citrus plants and formulation of a new fungicide. Finally, we also
      briefly describe a workflow which might be useful when research requires that
      model structures of target proteins are firstly generated (starting from genome
      sequences), followed by identification of ligand-target sites at the surface of
      those modeled structures, then application of procedures that adequately prepare
      both protein and ligand structures (the latter also involving filtration that
      satisfies acceptable adsorption/desorption/metabolism/excretion/toxicity [ADMET]
      parameters) for virtual high throughput screening (involving docking of ligands
      to indicated sites) and terminating by ranking of best pairs: target protein with
      selected ligand. 

PMID- 25961403
TI  - In Silico Protein-Protein Interactions: Avoiding Data and Method Biases Over
      Sensitivity and Specificity.
AB  - The study of protein-protein interactions (PPIs) can help researchers raise new
      hypotheses about an organism or disease and guide new experiments. Various
      methods for the identification and analysis of PPIs have been discussed in the
      literature. These methods are generally categorized as experimental or
      computational - each having its own advantages and disadvantages. Experimental
      methods provide insights into the real state of biological interactions but tend
      to be time-consuming and costly. Computational methods, on the other hand, can
      study thousands of PPIs at a very low cost and in much less time; however, the
      accuracy of such in silico prediction results heavily depends on the specific
      computational approach used. Furthermore, there is no gold standard for these
      computational methods; a method that works well for predicting one PPI may
      perform poorly (by generating false positives and false negatives) for a
      different PPI. Therefore, all such predictions must be carefully validated,
      preferably with experimental data. In this paper, we review the existing
      computational approaches and emphasize the use of biological data as inputs for
      accurate predictions of PPIs. We also discuss how such input datasets and
      approaches may influence the sensitivity and specificity of the predicted PPI
      networks. 

PMID- 25961404
TI  - Isolation and Characterization of L-Tryptophan Ammonia Lyase from Rubrivivax
      benzoatilyticus Strain JA2.
AB  - Ammonia lyase belongs to the family of enzymes that catalyzes the deamination of
      amino acids. Depending on the relative activity towards the substrates, L
      tryptophan ammonia lyase converts L-tryptophan to indole 3-acrylic acid and
      ammonia. Here, we isolated, purified, and characterized an L-tryptophan ammonia
      lyase from phototrophic purple non-sulfur bacterium Rubrivivax benzoatilyticus
      JA2. The isolated L-tryptophan ammonia lyase found to catalyze the reaction of L
      tryptophan to produce indole 3-acrylic acid and NH3. The enzyme is a
      heterotetramer and has the highest affinity to L-tryptophan. The optimum pH and
      temperature for the enzymatic action were 7.5 and 35 degrees C, respectively and
      the Km and Vmax were 40.4 +/- 23.1 nM and 0.964+/-0.2046 s(-1), respectively.
      These results suggest that the isolated enzyme is highly bioactive and could be a
      new class. Further molecular analyses are required to confirm the novelty of the
      enzyme. 

PMID- 25961405
TI  - A Disulfide Stabilized beta-Sandwich Defines the Structure of a New Cysteine
      Framework M-Superfamily Conotoxin.
AB  - The structure of a new cysteine framework (-C-CC-C-C-C-) "M"-superfamily
      conotoxin, Mo3964, shows it to have a beta-sandwich structure that is stabilized
      by inter-sheet cross disulfide bonds. Mo3964 decreases outward K(+) currents in
      rat dorsal root ganglion neurons and increases the reversal potential of the
      NaV1.2 channels. The structure of Mo3964 (PDB ID: 2MW7 ) is constructed from the
      disulfide connectivity pattern, i.e., 1-3, 2-5, and 4-6, that is hitherto
      undescribed for the "M"-superfamily conotoxins. The tertiary structural fold has
      not been described for any of the known conus peptides. NOE (549), dihedral angle
      (84), and hydrogen bond (28) restraints, obtained by measurement of (h3)JNC'
      scalar couplings, were used as input for structure calculation. The ensemble of
      structures showed a backbone root mean square deviation of 0.68 +/- 0.18 A, with
      87% and 13% of the backbone dihedral (phi, psi) angles lying in the most favored
      and additional allowed regions of the Ramachandran map. The conotoxin Mo3964
      represents a new bioactive peptide fold that is stabilized by disulfide bonds and
      adds to the existing repertoire of scaffolds that can be used to design stable
      bioactive peptide molecules. 

PMID- 25961406
TI  - CO2-Controllable Foaming and Emulsification Properties of the Stearic Acid Soap
      Systems.
AB  - Fatty acids, as a typical example of stearic acid, are a kind of cheap surfactant
      and have important applications. The challenging problem of industrial
      applications is their solubility. Herein, three organic amines-ethanolamine (EA),
      diethanolamine (DEA), and triethanolamine (TEA)-were used as counterions to
      increase the solubility of stearic acid, and the phase behaviors were
      investigated systematically. The phase diagrams were delineated at 25 and 50 
      degrees C, respectively. The phase-transition temperature was measured by
      differential scanning calorimetry (DSC) measurements, and the microstructures
      were vesicles and planar sheets observed by cryogenic transmission electron
      microscopy (cryo-TEM) observations. The apparent viscosity of the samples was
      determined by rheological characterizations. The values, rcmc, for the three
      systems were less than 30 mN.m(-1). Typical samples of bilayers used as foaming
      agents and emulsifiers were investigated for the foaming and emulsification
      assays. CO2 was introduced to change the solubility of stearic acid, inducing the
      transition of their surface activity and further achieving the goal of defoaming
      and demulsification. 

PMID- 25961407
TI  - Three-Dimensional Image of Cleavage Bodies in Nuclei Is Configured Using Gas
      Cluster Ion Beam with Time-of-Flight Secondary Ion Mass Spectrometry.
AB  - Structural variations of DNA in nuclei are deeply related with development,
      aging, and diseases through transcriptional regulation. In order to bare cross
      sections of samples maintaining sub-micron structures, an Ar2500(+)-gas cluster
      ion beam (GCIB) sputter was recently engineered. By introducing GCIB sputter to
      time-of-flight secondary ion mass spectrometry (TOF-SIMS), we analyzed the 3D
      configuration and chemical composition of subnuclear structures of pyramidal
      cells in the CA2 region in mouse brain hippocampus. Depth profiles of chemicals
      were analyzed as 3D distributions by combining topographic analyses. Signals
      corresponding to anions such as CN(-) and PO3(-) were distributed
      characteristically in the shape of cell organelles. CN(-) signals overlapped DAPI
      fluorescence signals corresponding to nuclei. The clusters shown by PO3(-) and
      those of adenine ions were colocalized inside nuclei revealed by the 3D
      reconstruction. Taking into account their size and their number in each nucleus,
      those clusters could be in the cleavage bodies, which are a kind of intranuclear
      structure. 

PMID- 25961408
TI  - Discovery of cancer drug targets by CRISPR-Cas9 screening of protein domains.
AB  - CRISPR-Cas9 genome editing technology holds great promise for discovering
      therapeutic targets in cancer and other diseases. Current screening strategies
      target CRISPR-Cas9-induced mutations to the 5' exons of candidate genes, but this
      approach often produces in-frame variants that retain functionality, which can
      obscure even strong genetic dependencies. Here we overcome this limitation by
      targeting CRISPR-Cas9 mutagenesis to exons encoding functional protein domains.
      This generates a higher proportion of null mutations and substantially increases
      the potency of negative selection. We also show that the magnitude of negative
      selection can be used to infer the functional importance of individual protein
      domains of interest. A screen of 192 chromatin regulatory domains in murine acute
      myeloid leukemia cells identifies six known drug targets and 19 additional
      dependencies. A broader application of this approach may allow comprehensive
      identification of protein domains that sustain cancer cells and are suitable for
      drug targeting. 

PMID- 25961409
TI  - Generation of articular chondrocytes from human pluripotent stem cells.
AB  - The replacement of articular cartilage through transplantation of chondrogenic
      cells or preformed cartilage tissue represents a potential new avenue for the
      treatment of degenerative joint diseases. Although many studies have described
      differentiation of human pluripotent stem cells (hPSCs) to the chondrogenic
      lineage, the generation of chondrocytes able to produce stable articular
      cartilage in vivo has not been demonstrated. Here we show that activation of the
      TGFbeta pathway in hPSC-derived chondrogenic progenitors promotes the efficient
      development of articular chondrocytes that can form stable cartilage tissue in
      vitro and in vivo. In contrast, chondrocytes specified by BMP4 signaling display
      characteristics of hypertrophy and give rise to cartilage tissues that initiate
      the endochondral ossification process in vivo. These findings provide a simple
      serum-free and efficient approach for the routine generation of hPSC-derived
      articular chondrocytes for modeling diseases of the joint and developing cell
      therapy approaches to treat them. 

PMID- 25961411
TI  - Highly active mesoporous ferrihydrite supported pt catalyst for formaldehyde
      removal at room temperature.
AB  - Ferrihydrite (Fh) supported Pt (Pt/Fh) catalyst was first prepared by combining
      microemulsion and NaBH4 reduction methods and investigated for room-temperature
      removal of formaldehyde (HCHO). It was found that the order of addition of Pt
      precursor and ferrihydrite in the preparation process has an important effect on
      the microstructure and performance of the catalyst. Pt/Fh was shown to be an
      efficient catalyst for complete oxidation of HCHO at room temperature, featuring
      higher activity than magnetite supported Pt (Pt/Fe3O4). Pt/Fh and Pt/Fe3O4
      exhibited much higher catalytic activity than Pt supported over calcined Fh and
      TiO2. The abundance of surface hydroxyls, high Pt dispersion and excellent
      adsorption performance of Fh are responsible for superior catalytic activity and
      stability of the Pt/Fh catalyst. This work provides some indications into the
      design and fabrication of the cost-effective and environmentally benign catalysts
      with excellent adsorption and catalytic oxidation performances for HCHO removal
      at room temperature. 

PMID- 25961410
TI  - Comprehensive analysis of the T-cell receptor beta chain gene in rhesus monkey by
      high throughput sequencing.
AB  - Profiling immune repertoires by high throughput sequencing enhances our
      understanding of immune system complexity and immune-related diseases in humans.
      Previously, cloning and Sanger sequencing identified limited numbers of T cell
      receptor (TCR) nucleotide sequences in rhesus monkeys, thus their full immune
      repertoire is unknown. We applied multiplex PCR and Illumina high throughput
      sequencing to study the TCRbeta of rhesus monkeys. We identified 1.26 million
      TCRbeta sequences corresponding to 643,570 unique TCRbeta sequences and 270,557
      unique complementarity-determining region 3 (CDR3) gene sequences. Precise
      measurements of CDR3 length distribution, CDR3 amino acid distribution, length
      distribution of N nucleotide of junctional region, and TCRV and TCRJ gene usage
      preferences were performed. A comprehensive profile of rhesus monkey immune
      repertoire might aid human infectious disease studies using rhesus monkeys. 

PMID- 25961412
TI  - Automated determination of fibrillar structures by simultaneous model building
      and fiber diffraction refinement.
AB  - For highly oriented fibrillar molecules, three-dimensional structures can often
      be determined from X-ray fiber diffraction data. However, because of limited
      information content, structure determination and validation can be challenging.
      We demonstrate that automated structure determination of protein fibers can be
      achieved by guiding the building of macromolecular models with fiber diffraction
      data. We illustrate the power of our approach by determining the structures of
      six bacteriophage viruses de novo using fiber diffraction data alone and together
      with solid-state NMR data. Furthermore, we demonstrate the feasibility of
      molecular replacement from monomeric and fibrillar templates by solving the
      structure of a plant virus using homology modeling and protein-protein docking.
      The generated models explain the experimental data to the same degree as
      deposited reference structures but with improved structural quality. We also
      developed a cross-validation method for model selection. The results highlight
      the power of fiber diffraction data as structural constraints. 

PMID- 25961413
TI  - Structural analysis of multicellular organisms with cryo-electron tomography.
AB  - We developed a method for visualizing tissues from multicellular organisms using
      cryo-electron tomography. Our protocol involves vitrifying samples with high
      pressure freezing, thinning them with cryo-FIB-SEM (focused-ion-beam scanning
      electron microscopy) and applying fiducial gold markers under cryogenic
      conditions to the lamellae post-milling. We applied this protocol to acquire
      tomograms of vitrified Caenorhabditis elegans embryos and worms, which showed the
      intracellular organization of selected tissues at particular developmental stages
      in otherwise intact specimens. 

PMID- 25961414
TI  - 3D high- and super-resolution imaging using single-objective SPIM.
AB  - Single-objective selective-plane illumination microscopy (soSPIM) is achieved
      with micromirrored cavities combined with a laser beam-steering unit installed on
      a standard inverted microscope. The illumination and detection are done through
      the same objective. soSPIM can be used with standard sample preparations and
      features high background rejection and efficient photon collection, allowing for
      3D single-molecule-based super-resolution imaging of whole cells or cell
      aggregates. Using larger mirrors enabled us to broaden the capabilities of our
      system to image Drosophila embryos. 

PMID- 25961415
TI  - Acceleration Effects of Phosphine Ligands on the Rhodium-Catalyzed
      Dehydrogenative Silylation and Germylation of Unactivated C(sp(3))-H Bonds.
AB  - The current work describes the marked rate of acceleration caused by phosphine
      ligands on the rhodium-catalyzed dehydrogenative silylation and germylation of
      unactivated C(sp(3))-H bonds. The reactivity was affected by the steric and
      electronic nature of the phosphine ligands. The use of the bulky and electron
      rich diphosphine ligand (R)-DTBM-SEGPHOS was highly effective to yield the
      dehydrogenative silylation products selectively in the presence of a hydrogen
      acceptor. An appropriate choice of C2-symmetric chiral diphosphine ligand enables
      the asymmetric dehydrogenative silylation via the enantioselective
      desymmetrization of the C(sp(3))-H bond. The unprecedented catalytic germylation
      of C(sp(3))-H bonds with dehydrogenation was also examined with the combination
      of the rhodium complex and a wide bite angle diphosphine ligand to provide the
      corresponding 2,3-dihydrobenzo[b]germoles in good yield. 

PMID- 25961416
TI  - Tetramethyleneethane Equivalents: Recursive Reagents for Serialized
      Cycloadditions.
AB  - New reactions and reagents that allow for multiple bond-forming events per
      synthetic operation are required to achieve structural complexity and thus value
      with step-, time-, cost-, and waste-economy. Here we report a new class of
      reagents that function like tetramethyleneethane (TME), allowing for back-to-back
      [4 + 2] cycloadditions, thereby amplifying the complexity-increasing benefits of
      Diels-Alder and metal-catalyzed cycloadditions. The parent recursive reagent, 2,3
      dimethylene-4-trimethylsilylbutan-1-ol (DMTB), is readily available from the
      metathesis of ethylene and THP-protected 4-trimethylsilylbutyn-1-ol. DMTB and
      related reagents engage diverse dienophiles in an initial Diels-Alder or metal
      catalyzed [4 + 2] cycloaddition, triggering a subsequent vinylogous Peterson
      elimination that recursively generates a new diene for a second cycloaddition.
      Overall, this multicomponent catalytic cascade produces in one operation carbo-
      and heterobicyclic building blocks for the synthesis of a variety of natural
      products, therapeutic leads, imaging agents, and materials. Its application to
      the three step synthesis of a new solvatochromic fluorophore, N-ethyl(6-N,N
      dimethylaminoanthracene-2,3-dicarboximide) (6-DMA), and the photophysical
      characterization of this fluorophore are described. 

PMID- 25961417
TI  - Phase transitions of the ionic Hubbard model on the honeycomb lattice.
AB  - Many-body problem on the honeycomb lattice systems have been the subject of
      considerable experimental and theoretical interest. Here we investigate the phase
      transitions of the ionic Hubbard model on the honeycomb lattice with an alternate
      ionic potential for the half filling and hole doping cases by means of cellular
      dynamical mean field theory combining with continue time quantum Monte Carlo as
      an impurity solver. At half filling, as the increase of the interaction at a
      fixed ionic potential, we find the single particle gap decreases firstly, reaches
      a minimum at a critical interaction Uc, then increases upturn. At Uc, there is a
      band insulator to Mott insulator transition accompanying with the presence of the
      antiferromagnetic order. Away from half filing, the system shows three phases for
      the different values of hole density and interaction, paramagnetic metal,
      antiferromagnetic metal and ferromagnetic metal. Further, we present the
      staggered particle number, the double occupancy, the staggered magnetization, the
      uniform magnetization and the single particle spectral properties, which exhibit
      characteristic features for those phases.

PMID- 25961418
TI  - DNA Nanostructures as Programmable Biomolecular Scaffolds.
AB  - This Review focuses on how to use DNA nanostructures as scaffolds to organize
      biological molecules. First, we introduce the use of structural DNA
      nanotechnology to engineer rationally designed nanostructures. Second, we survey
      approaches used to generate protein-DNA conjugates. Third, we discuss studies
      exploring DNA scaffolds to create DNA nanodevices to analyze protein structures,
      to engineer enzyme pathways, to create artificial light-harvesting systems, and
      to generate nanomachines in vitro and in vivo. Future challenges and perspectives
      of using DNA nanostructures as programmable biomolecular scaffolds are addressed
      at the end. 

PMID- 25961419
TI  - High aspect ratio conjugated polymer nanowires for high performance field-effect
      transistors and phototransistors.
AB  - We synthesized a highly crystalline DPP-based polymer, DPPBTSPE, which contained
      1,2-bis(5-(thiophen-2-yl)selenophen-2-yl)ethene as a planar and rigid electron
      donating group. High- and low-molecular weight (MW) DPPBTSPE fractions were
      collected by Soxhlet extraction and were employed to investigate their unique
      charge transport properties in macroscopic films and single crystalline polymer
      nanowire (SC-PNW), respectively. The low-MW polymer could provide well-isolated
      and high aspect ratio SC-PNWs, in which the direction of pi-pi stacking was
      perpendicular to the wire growing axis. The field effect transistors made of SC
      PNWs exhibited remarkably high carrier mobility of 24 cm(2) V(-1) s(-1). In
      addition, phototransistors (PTs) made of SC-PNW showed very high performance in
      terms of photoresponsivity (R) and photoswitching ratio (P). The average R of the
      SC PNW-based PTs were in the range of 160-170 A W(-1) and the maximum R was
      measured at 1920 A W(-1), which is almost three orders higher than that of thin
      film-based PT device. 

PMID- 25961421
TI  - Physical exercise reduces synthesis of ADMA, SDMA, and L-Arg.
AB  - Increased levels of asymmetric dimethylarginine (ADMA), symmetric
      dimethylarginine (SDMA) and low plasma level of L-arginine (L-ARG) are all
      conditions likely to decrease nitric oxide (NO) production. Aim of this study is
      to evaluate ADMA, SDMA, and L-ARG plasmatic levels before and after physical
      exercise in patients with coronary artery disease (CAD). We studied 30 patient
      with mean age 52 + 4.5 years. After inclusion in the study, before the execution
      of physical exercise, heparinized blood sample was drawn from an indwelling
      arterial line for determination of ADMA, L-ARG and SDMA (baseline values).
      Subsequently a blood sample was drawn after the physical exercise. The mean
      plasma concentrations of ADMA (0.68 + 0.06 vs 0.48 + 0.05 umol/L) and SDMA (0.45
      + 0.03 vs 0.30 + 0.03 umol/L) were significantly lower after physical exercise in
      comparison to baseline value, while L-ARG mean levels were increased (44.20 +
      10.5 vs 74.13 + 11.2 umol/L). Physical exercise has a beneficial effect by
      reducing plasmatic ADMA and SDMA levels, and increasing L-ARG substrate for
      endothelial NO. 

PMID- 25961422
TI  - Induction of crossover by introduction of aro554:Tn10 into Salmonella chromosome.
AB  - One of the ancient methods for the generation of bacterial mutants was to insert
      the composite transposable elements (e.g. Tn10) flanked by desired gene
      sequences, into the bacterial chromosome. This mechanism of DNA integrating into
      a chromosome can sometimes not only lead to the creation of desired mutants but
      also induced other recombination event within the chromosome. Several studies
      have reported alterations such as deletion, insertion, inversion and both
      deletion/inversion in the bacterial chromosome due to the insertion of composite
      transposable elements. In this study it has been found that a Tn10 mutagenesis
      event not only leads to the inactivation of desired gene (?aorA), and
      consequential deletion of other genes upstream of aroA and insertion of IS10,
      also has resulted in a large-scale chromosomal rearrangement in the Salmonella
      Typhimurium chromosome. This rearrangement consists of exchange of genetic
      material between the 10 minute and the 19 minute on a circular chromosomal map
      (approximately 440 kbps), possibly due to crossover between the two regions.
      Results from this study are the first evidence of such a large scale
      rearrangement in the bacterial genome due to the insertion of transposable
      elements. 

PMID- 25961420
TI  - Remote ischaemic conditioning: cardiac protection from afar.
AB  - For patients with ischaemic heart disease, remote ischaemic conditioning may
      offer an innovative, non-invasive and virtually cost-free therapy for protecting
      the myocardium against the detrimental effects of acute ischaemia-reperfusion
      injury, preserving cardiac function and improving clinical outcomes. The
      intriguing phenomenon of remote ischaemic conditioning was first discovered over
      20 years ago, when it was shown that the heart could be rendered resistant to
      acute ischaemia-reperfusion injury by applying one or more cycles of brief
      ischaemia and reperfusion to an organ or tissue away from the heart - initially
      termed 'cardioprotection at a distance'. Subsequent pre-clinical and then
      clinical studies made the important discovery that remote ischaemic conditioning
      could be elicited non-invasively, by inducing brief ischaemia and reperfusion to
      the upper or lower limb using a cuff. The actual mechanism underlying remote
      ischaemic conditioning cardioprotection remains unclear, although a neuro
      hormonal pathway has been implicated. Since its initial discovery in 1993, the
      first proof-of-concept clinical studies of remote ischaemic conditioning followed
      in 2006, and now multicentre clinical outcome studies are underway. In this
      review article, we explore the potential mechanisms underlying this academic
      curiosity, and assess the success of its application in the clinical setting. 

PMID- 25961423
TI  - Mechanisms of PDGFRalpha promiscuity and PDGFRbeta specificity in association
      with PDGFB.
AB  - Platelet-derived growth factor receptor alpha (PDGFRalpha) interacts with PDGFs
      A, B, C and AB, while PDGFRbeta binds to PDGFs B and D, thus suggesting that
      PDGFRalpha is more promiscuous than PDGFRbeta. The structural analysis of
      PDGFRalpha-PDGFA and PDGFRalpha-PDGFB complexes and a molecular explanation for
      the promiscuity of PDGFRalpha and the specificity of PDGFRbeta remain unclear. In
      the present study, we modeled the three extracellular domains of PDGFRalpha using
      a previous crystallographic structure of PDGFRbeta as a template. Additionally,
      we analyzed the interacting residues of PDGFRalpha-PDGFA and PDGFRalpha-PDGFB
      complexes using docking simulations. The validation of the resulting complexes
      was evaluated by molecular dynamics simulations. Structural analysis revealed
      that changes of non-aromatic amino acids in PDGFRalpha to aromatic amino acids in
      PDGFRbeta (I139F, P267F and N204Y) may be involved in the promiscuity of
      PDGFRalpha. Indeed, substitution of amino acids with few probabilities of rotamer
      changes in PDGFRbeta (M133A, N163E and N179S) and energy stability due to the
      formation of hydrogen bond in PDGFRbeta could explain the specificity of
      PDGFRbeta. These results may be used as an input for a better and more specific
      drug and peptide design targeting diseases related with the malfunction of PDGFs
      and PDGFRalpha such as cancer and atherosclerosis. 

PMID- 25961424
TI  - Ambient Environmental risk factors for childhood wheezing illness.
AB  - It is a great consensus in the scientific community that environmental factors,
      such as weather conditions and ambient air pollution, have vital impacts on
      respiratory diseases. Further, these factors imply the potential to have many
      significant impacts on aeroallergens, and therefore related diseases such as
      asthma and allergic rhinitis. The impacts are more pronounced in sensitive groups
      of population, such as children and elderly, living in urbanized areas. Over the
      last three decades, studies have shown changes in production, dispersion and
      allergen content of pollen and spores, which may be region- and species-specific.
      In addition, these changes may have been influenced by air pollutants interacting
      directly with pollen. It is not easy to evaluate the impact of climate change and
      air pollution on the prevalence of asthma in general and on the timing of asthma
      exacerbations. However, the global rise in asthma prevalence and severity
      suggests that air pollution and climate changes could be contributing. The
      objective of this review is to summarize the environmental impacts on pulmonary
      diseases in children based on recent literature over the world. 

PMID- 25961425
TI  - Perception of dyspnea in children with asthma.
AB  - The subjective experience of discomfort in breathing, termed dyspnea (or
      breathlessness), is a symptom with multifactorial causes of highly complex and
      largely undefined psycho-physiologic mechanism(s). There are at least three
      discrete qualities of dyspnea likely corresponding to different types of
      respiratory stress and separate underlying mechanisms. Perception of dyspnea can
      be measured by diverse means; however, none of these scales has been standardized
      in children. In general, the same degree of bronchoconstriction causes various
      levels of perception of dyspnea in different patients. There are large
      discrepancies among patients in subjective rating of the severity of dyspnea and
      objective measurement of lung function. Since reporting symptoms is an integral
      part of therapeutic management of asthma, poor perception of dyspnea may lead to
      delayed diagnosis and undertreatment of the disease. 

PMID- 25961426
TI  - Bioavailability of different dietary supplemental methionine sources in animals.
AB  - Dietary methionine is indispensable for animal maintenance, growth and
      development. L-methionine (L-Met), and its synthetic forms DL-methionine (DL-Met)
      and 2-hydroxy-4 (methylthio) butanoic acid (HMTBA) are common supplemental
      methionine sources in animal diets. There are different characteristics for
      cellular absorption, transport, metabolism and bio-efficiency between these three
      dietary methionine sources. Moreover, there are differences in their utilization
      among various species such as chickens, pigs and ruminants. As a methionine
      precursor, HMTBA is efficacious in the promotion of growth in animals. It is
      absorbed mainly by monocarboxylate transporter 1 (MCT1), coupled with the
      activity of the Na(+)/H(+) exchanger (NHE3), while DL-Met uptake occurs via
      multiple carrier-mediated systems. Liver, kidney and small intestine can
      metabolize D-Met and HMTBA to L-Met through oxidation and transamination. In
      ruminants, the non-hepatic tissues act as major sites of HMTBA conversion, which
      are different from that in chickens and pigs. HMTBA also has additional benefits
      in anti-oxidation. Understanding the characteristics of uptake and metabolism of
      different methionine sources will greatly benefit the industry and bioscience
      research. 

PMID- 25961427
TI  - Kidney transplantation in patients with history of malignancy: Time to rethink
      the guidelines?
AB  - A history of malignancy is often considered a contraindication for kidney
      transplantation. While the desire to transplant a 'cancer-free' patient is
      understandable, the current approach neglects the heterogeneity in the natural
      history of cancers, even within a given tumor type. The information used to
      formulate current guidelines are dated and fail to reflect the vast resource of
      modern oncology clinical trials data that should more accurately predict the
      expected overall survival and recurrence risk of cancer patients. The expected
      survival for many cancer patients excluded by current guidelines compares
      favorably with other conditions considered acceptable for transplantation. This
      review will suggest that close collaboration between transplant teams and
      oncologists can increase the appropriate use of renal transplantation in cancer
      patients.

PMID- 25961428
TI  - Near-Infrared-to-Visible Photon Upconversion Enabled by Conjugated Porphyrinic
      Sensitizers under Low-Power Noncoherent Illumination.
AB  - We report four supermolecular chromophores based on (porphinato)zinc(II) (PZn)
      and (polypyridyl)metal units bridged via ethyne connectivity (Pyr1RuPZn2,
      Pyr1RuPZnRuPyr1, Pyr1RuPZn2RuPyr1, and OsPZn2Os) that fulfill critical sensitizer
      requirements for NIR-to-vis triplet-triplet annihilation upconversion (TTA-UC)
      photochemistry. These NIR sensitizers feature: (i) broad, high oscillator
      strength NIR absorptivity (700 nm < lambda(max(NIR)) < 770 nm; 6 * 10(4) M(-1)
      cm(-1) < extinction coefficient (lambda(max(NIR))) < 1.6 * 10(5) M(-1) cm(-1);
      820 cm(-1) < fwhm < 1700 cm(-1)); (ii) substantial intersystem crossing quantum
      yields; (iii) long, microsecond time scale T1 state lifetimes; and (iv) triplet
      states that are energetically poised for exergonic energy transfer to the
      molecular annihilator (rubrene). Using low-power noncoherent illumination at
      power densities (1-10 mW cm(-2)) similar to that of terrestrial solar photon
      illumination conditions, we demonstrate that Pyr1RuPZn2, Pyr1RuPZn2RuPyr1, and
      Pyr1RuPZnRuPyr1 sensitizers can be used in combination with the rubrene
      acceptor/annihilator to achieve TTA-UC: these studies represent the first
      examples whereby a low-power noncoherent NIR light source drives NIR-to-visible
      upconverted fluorescence centered in a spectral window within the bandgap of
      amorphous silicon.

PMID- 25961429
TI  - Grand Canonical Monte Carlo Simulations Guided by an Analytic Equation of State
      Transferable Anisotropic Mie Potentials for Ethers.
AB  - In this study, we propose using an analytical equation of state for guiding
      molecular simulations in the grand canonical ensemble. Molecular simulations in
      the grand canonical ensemble deliver phase equilibrium properties with low
      statistical uncertainty. The entire phase envelope can be obtained when
      histograms of several simulations along the phase envelope are combined. In this
      study, we explore the use of an analytical equation of state for defining
      chemical potentials, temperatures, and intervals of molecule numbers for
      simulations in the grand canonical ensemble, such that the phase envelope is
      traced. We limit particle numbers to intervals and ensure even sampling of
      molecule numbers in each interval by applying a bias potential determined from
      transition-matrix sampling. The methodology is described for pure components and
      binary mixtures. We apply the simulation method to develop parameters of the
      transferable anisotropic Mie (TAMie) force field for ethers. We find that the
      partial charges optimized individually for diethyl ether and for dipropyl ether
      differ substantially from the partial charges optimized simultaneously to both
      substances. The concept of transferable partial charges is thus a significant
      assumption. For developing the (TAMie) force field, we constrained the partial
      charge to a range, where individually optimized partial charges were found. 

PMID- 25961430
TI  - Detailed Biological Profiling of a Photoactivated and Apoptosis Inducing pdppz
      Ruthenium(II) Polypyridyl Complex in Cancer Cells.
AB  - Ruthenium polypyridyl complexes show great promise as new photodynamic therapy
      (PDT) agents. However, a lack of detailed understanding of their mode of action
      in cells poses a challenge to their development. We have designed a new Ru(II)
      PDT candidate that efficiently enters cells by incorporation of the lipophilic
      aromatic pdppz ([2,3-h]dipyrido[3,2-a:2',3'-c]phenazine) ligand and exhibits
      photoactivity through incorporation of 1,4,5,8-tetraazaphenanthrene ancillary
      ligands. Its photoreactivity toward biomolecules was studied in vitro, where
      light activation caused DNA cleavage. Cellular internalization occurred via an
      energy dependent mechanism. Confocal and transmission electron microscopy
      revealed that the complex localizes in various organelles, including the
      mitochondria. The complex is nontoxic in the dark, with cellular clearance within
      96 h; however, upon visible light activation it induces caspase-dependent and
      reactive-oxygen-species-dependent apoptosis, with low micromolar IC50 values.
      This investigation greatly increases our understanding of such systems in
      cellulo, aiding development and realization of their application in cancer
      therapy. 

PMID- 25961432
TI  - Development of large-scale size-controlled adult pancreatic progenitor cell
      clusters by an inkjet-printing technique.
AB  - The generation of transplantable beta-cells from pancreatic progenitor cells
      (PPCs) could serve as an ideal cell-based therapy for diabetes. Because the
      transplant efficiency depends on the size of islet-like clusters, it becomes one
      of the key research topics to produce PPCs with controlled cluster sizes in a
      scalable manner. In this study, we used inkjet printing to pattern biogenic
      nanoparticles, i.e., mutant tobacco mosaic virus (TMV), with different spot sizes
      to support the formation of multicellular clusters by PPCs. We successfully
      achieved TMV particle patterns with variable features and sizes by adjusting the
      surface wettability and printing speed. The spot sizes of cell-adhesive TMV
      mutant arrays were in the range of 50-150 MUm diameter. Mouse PPCs were seeded on
      the TMV-RGD (arginine-glycine-aspartate)-patterned polystyrene (PS) substrate,
      which consists of areas that either favor (TMV-RGD) or prohibit (bare PS) cell
      adhesion. The PPCs stably attached, proliferated on top of the TMV-RGD support,
      thus resulting in the formation of uniform and confluent PPC clusters.
      Furthermore, the aggregated PPCs also maintained their multipotency and were
      positive for E-cadherin, indicating that the formation of cell-cell junctions is
      critical for enhanced cell-cell contact. 

PMID- 25961433
TI  - Strain-driven direct cross-aldol and -ketol reactions of four-membered
      heterocyclic ketones.
AB  - Owing to the ring strain and alpha-heteroatom effect, the four-membered
      heterocyclic ketones can undergo direct cross-aldol and -ketol reactions without
      the need for preformed enol or "enolate-like" intermediates. Besides the
      organocatalyzed cross-ketol addition onto their highly active carbonyl group,
      their ability to act as a nucleophilic donor has also been explored. As a result,
      a number of discrete aldol adducts were synthesized and the distinct reactivities
      were successfully combined into a double-aldol one-pot reaction. 

PMID- 25961431
TI  - Cardiovascular risk factors and metabolic syndrome in people with established
      psychotic illnesses: baseline data from the IMPaCT randomized controlled trial.
AB  - BACKGROUND: The aims of the study were to determine the prevalence of
      cardiometabolic risk factors and establish the proportion of people with
      psychosis meeting criteria for the metabolic syndrome (MetS). The study also
      aimed to identify the key lifestyle behaviours associated with increased risk of
      the MetS and to investigate whether the MetS is associated with illness severity
      and degree of functional impairment. METHOD: Baseline data were collected as part
      of a large randomized controlled trial (IMPaCT RCT). The study took place within
      community mental health teams in five Mental Health NHS Trusts in urban and rural
      locations across England. A total of 450 randomly selected out-patients, aged 18
      65 years, with an established psychotic illness were recruited. We ascertained
      the prevalence rates of cardiometabolic risk factors, illness severity and
      functional impairment and calculated rates of the MetS, using International
      Diabetes Federation (IDF) and National Cholesterol Education Program Third Adult
      Treatment Panel criteria. RESULTS: High rates of cardiometabolic risk factors
      were found. Nearly all women and most men had waist circumference exceeding the
      IDF threshold for central obesity. Half the sample was obese (body mass index >=
      30 kg/m2) and a fifth met the criteria for type 2 diabetes mellitus. Females were
      more likely to be obese than males (61% v. 42%, p < 0.001). Of the 308 patients
      with complete laboratory measures, 57% (n = 175) met the IDF criteria for the
      MetS. CONCLUSIONS: In the UK, the prevalence of cardiometabolic risk factors in
      individuals with psychotic illnesses is much higher than that observed in
      national general population studies as well as in most international studies of
      patients with psychosis.

PMID- 25961434
TI  - MiR-744 functions as a proto-oncogene in nasopharyngeal carcinoma progression and
      metastasis via transcriptional control of ARHGAP5.
AB  - Nasopharyngeal carcinoma (NPC) is a highly invasive and metastasis-prone
      epithelial cancer. The paucity of effective treatment strategies for recurrent
      and metastatic NPC is the major cause for stagnating survival rate of NPC.
      Therefore, it's urgent to understand the molecular mechanisms underlying NPC
      progression and identify novel avenues for targeted therapy. It has emerged
      recently that microRNAs are potential pro-tumorigenic or tumor-suppressive
      factors that participate in oncogenesis. In this study, we found that miR-744
      expression was upregulated in NPC specimens compared to nasopharyngeal epithelium
      (NPE) tissue, and miR- 744 upregulation was significantly associated with TNM
      stage, tumorigenesis and metastasis. Functional studies revealed that miR-744
      acts as a novel tumor promotor in NPC. Moreover, we determined that miR-744
      targets ARHGAP5 (Rho GTPase activating protein 5), a protumorigenic gene, by
      directly interacting with its promoter and thereby regulating its expression at
      transcriptional level. Reintroduction of ARHGAP5 resembled the effects of miR-744
      and silencing of ARHGAP5 clearly abrogated miR-744-induced enhancement of cell
      migration and invasion. High level of ARHGAP5 was positively correlated with that
      of miR-744 and with advanced stages of NPC, as well as with lymph node
      metastasis. Taken together, these data reveal for the first time that miR-744
      exerts its proto-oncogenic function by directly targeting ARHGAP5 promoter. This
      newly identified miR-744/ARHGAP5 pathway provides further insight into the
      progression and metastasis of NPC and indicates potential novel therapeutic
      targets for NPC. 

PMID- 25961435
TI  - Not Breathing Easier With the US FDA's Ban on Chlorofluorocarbons in Inhalers.

PMID- 25961436
TI  - Clinical Trials of Therapies for Amyotrophic Lateral Sclerosis: One Size Does Not
      Fit All.

PMID- 25961437
TI  - Risks of Different Testosterone Preparations: Too Much, Too Little, Just Right.

PMID- 25961439
TI  - Nutcracker and jackhammer esophagus treatment: a three-case survey, including two
      novel cases of eosinophilic infiltration into the muscularis propria.
AB  - Nutcracker esophagus and jackhammer esophagus are largely unknown motility
      disorders, also sometimes called hypertensive and hypercontractile peristalsis,
      respectively. There is currently no standardized diagnostic or management plan
      for these diseases. Here, we report on three patients with jackhammer/nutcracker
      esophagus who were treated with either peroral endoscopic myotomy or a systemic
      steroid regimen, focusing particularly on two novel presentations of nutcracker
      and jackhammer esophagus involving eosinophilic infiltration into the muscularis
      propria, and their responses to both interventions. 

PMID- 25961438
TI  - Characteristics and Clinical Management of a Cluster of 3 Patients With Ebola
      Virus Disease, Including the First Domestically Acquired Cases in the United
      States.
AB  - BACKGROUND: More than 26,000 cases of Ebola virus disease (EVD) have been
      reported in western Africa, with high mortality. Several patients have been
      medically evacuated to hospitals in the United States and Europe. Detailed
      clinical data are limited on the clinical course and management of patients with
      EVD outside western Africa. OBJECTIVE: To describe the clinical characteristics
      and management of a cluster of patients with EVD, including the first cases of
      Ebola virus (EBOV) infection acquired in the United States. DESIGN: Retrospective
      clinical case series. SETTING: Three U.S. hospitals in September and October
      2014. PATIENTS: First imported EVD case identified in the United States and 2
      secondary EVD cases acquired in the United States in critical care nurses who
      cared for the index case patient. MEASUREMENTS: Clinical recovery, EBOV RNA
      level, resolution of Ebola viremia, survival with discharge from hospital, or
      death. RESULTS: The index patient had high EBOV RNA levels, developed respiratory
      and renal failure requiring critical care support, and died. Both patients with
      secondary EBOV infection had nonspecific signs and symptoms and developed
      moderate illness; EBOV RNA levels were moderate, and both patients recovered.
      LIMITATION: Both surviving patients received uncontrolled treatment with multiple
      investigational agents, including convalescent plasma, which limits
      generalizability of the results. CONCLUSION: Early diagnosis, prompt initiation
      of supportive medical care, and moderate clinical illness likely contributed to
      successful outcomes in both survivors. The inability to determine the potential
      benefit of investigational therapies and the effect of patient-specific factors
      that may have contributed to less severe illness highlight the need for
      controlled clinical studies of these interventions, especially in the setting of
      a high level of supportive medical care. PRIMARY FUNDING SOURCE: None.

PMID- 25961440
TI  - Microscopic colitis: a misnomer for a clearly defined entity?
AB  - In recent years, several endoscopic features of microscopic colitis have been
      noted. The pickup of these on colonoscopy depends on local expertise, endoscopic
      technology, and case volume. As the incidence of microscopic colitis has
      increased, we wanted to draw attention to endoscopists' ability to recognize such
      findings. We present eight cases of biopsy-proven microscopic colitis which
      demonstrate the spectrum of endoscopic findings. Endoscopists should actively
      search for such findings and target their biopsies, as new high-definition
      colonoscopes with sharper images, zoom capabilities, and high resolution allow a
      new vision into this syndrome. 

PMID- 25961441
TI  - Single-channel endoscopic closure of large endoscopy-related perforations.
AB  - BACKGROUND AND STUDY AIMS: Gastrointestinal endoscopy procedures, such as
      endoscopic retrograde cholangiopancreatography (ERCP), endoscopic submucosal
      dissection (ESD), and colonoscopy are widely used for the diagnosis or treatment
      of digestive diseases. Perforation is a rare but potentially lethal complication.
      Large perforations usually require immediate endoscopic or surgical repair.
      Endoscopic closure using a nylon loop pouch suture is usually performed with a
      double-channel endoscope. This paper describes the endoscopic closure of large
      procedure-related perforations using a single-channel endoscope. PATIENTS AND
      METHODS: A total of 10 patients with large perforations (2.5 - 4.0 cm), which
      occurred during ERCP, ESD, or colonoscopy, were treated using the single-channel
      endoscope technique. RESULTS: All perforations were successfully closed using a
      nylon loop pouch suture through the single-channel endoscope. No surgery or
      further endoscopic intervention was required. CONCLUSIONS: Nylon loop pouch
      suture through a single-channel endoscope was easy to perform and was feasible
      for the closure of large gastrointestinal perforations.

PMID- 25961442
TI  - Endoscopically inserted nasobiliary catheters for high dose-rate brachytherapy as
      part of neoadjuvant therapy for perihilar cholangiocarcinoma.
AB  - BACKGROUND AND AIM: Selected patients with unresectable perihilar
      cholangiocarcinoma can undergo neoadjuvant chemoradiotherapy followed by liver
      transplantation, which has been shown to improve survival. The aim of this study
      was to determine the feasibility and safety of endoscopic transpapillary
      insertion of nasobiliary tubes (NBTs) and brachytherapy catheters for high dose
      rate (HDR) brachytherapy as part of this neoadjuvant chemoradiotherapy. PATIENTS
      AND METHODS: Medical records of patients undergoing biliary brachytherapy for
      hilar cholangiocarcinoma at the Mayo Clinic, Rochester were reviewed. Patients
      were treated with curative intent using external beam radiotherapy (4500 cGy),
      chemotherapy (5-FU or capecitabine), and HDR brachytherapy (930 - 1600 cGy in one
      to four fractions delivered over 1 - 2 days) prior to planned liver
      transplantation. RESULTS: Between 2009 and 2013, 40 patients underwent biliary
      HDR brachytherapy via endoscopically placed NBTs (8.5 - 10 Fr). Patients had a
      median age of 55 years (range 28 - 68); 25 patients (62.5 %) had primary
      sclerosing cholangitis. Prior to therapy, 29 patients (72.5 %) had plastic
      stents, two (5 %) had metal stents, and nine (22.5 %) had no stents. Bilateral
      NBTs were placed in five patients (12.5 %). NBT/brachytherapy catheter
      displacement was seen in eight patients (20 %) - five intraprocedure and three
      post-procedure. A radiotherapy error and NBT kinking each occurred once. Post
      procedure adverse events included: cholangitis (n = 5; 12.5 %), severe abdominal
      pain (n = 3; 7.5 %), duodenopathy (n = 3; 7.5 %), gastropathy (n = 3; 7.5 %), and
      both duodenopathy and gastropathy (n = 2; 5 %). CONCLUSION: HDR biliary
      brachytherapy administered via endoscopically placed NBTs and brachytherapy
      catheters is technically feasible and appears reasonably safe in selected
      patients with unresectable perihilar cholangiocarcinoma.

PMID- 25961443
TI  - Endoscopic ultrasound-guided biliary drainage after failed ERCP: cumulative
      experience of 101 procedures at a single center.
AB  - BACKGROUND AND STUDY AIM: Endoscopic ultrasound (EUS)-guided biliary access is an
      alternative to percutaneous access after failed endoscopic retrograde
      cholangiopancreatography (ERCP). This report presents 7 years' cumulative
      experience of EUS-guided biliary drainage for obstructive jaundice in patients
      with failed ERCP. PATIENTS AND METHODS: Between February 2006 and February 2013,
      101 patients (malignant = 98, benign = 3) with previous failed ERCP underwent an
      EUS intra- or extrahepatic approach with transluminal stenting or an EUS-guided
      rendezvous procedure with transpapillary stent placement. A single endoscopist
      performed all procedures. RESULTS: A total of 71 patients underwent the
      intrahepatic approach (66 hepatogastrostomies and 5 EUS-guided rendezvous), and
      30 underwent the extrahepatic approach (26 choledochoduodenostomies, 1
      choledochojejunostomy, 1 choledochoantrostomy, and 2 EUS-guided
      cholangiographies). Technical and clinical success rates were 98.0 % and 92.1 %,
      respectively. There was no difference in efficacy between hepatogastrostomies and
      choledochoduodenostomies (94 % vs. 90 %; P = 0.69) or in major complications
      (10.6 % vs. 6.7 %; P = 1). Adverse events occurred in 12 patients (11.9 %): 10 in
      the hepatogastrostomy group (2 limited pneumoperitoneum, 1 hepatic hematoma, 5
      bile leakage, 2 sepsis), and 2 in the choledochoduodenostomy group (1
      arteriobiliary fistula and 1 sepsis). There were six procedure-related deaths,
      five among the first 50 patients and one among the last 51 patients.
      Hepatogastrostomy vs. choledochoduodenostomy, plastic vs. metal stenting, stent
      in-stent vs. 1 stent, nasobiliary drain, or postoperative octreotide infusion
      were not prognostic of bile leakage. CONCLUSION: EUS-guided biliary drainage is
      an efficient technique, but is associated with significant morbidity that seems
      to decrease with the learning curve. It should be performed in tertiary care
      centers in selected patients. Prospective randomized studies are needed to
      compare EUS-guided biliary drainage with percutaneous transhepatic
      cholangiography drainage.

PMID- 25961444
TI  - Risk of progression for incidental small subepithelial tumors in the upper
      gastrointestinal tract.
AB  - BACKGROUND AND STUDY AIMS: Subepithelial tumor is a relatively common finding in
      upper gastrointestinal endoscopy. This study aimed to evaluate the natural course
      of incidentally detected small subepithelial tumors in the upper gastrointestinal
      tract and to analyze risk factors for increase in the size of such tumors.
      PATIENTS AND METHODS: Medical records of 1684 patients with subepithelial tumors
      in the upper gastrointestinal tract incidentally detected between 2004 and 2013
      were retrospectively reviewed. If serial follow-up endoscopy showed significant
      size increase, endoscopic or surgical resection was recommended because of
      possibility of malignant change. RESULTS: 954 participants with subepithelial
      tumors underwent serial upper gastrointestinal endoscopy for a period > 6 months.
      Initial mean size of subepithelial tumors was 8.7 mm (range 1 - 35 mm). During a
      mean follow-up of 47.3 months (range 6 - 118 months), lesion size was unchanged
      in 920 participants (96.4 %), and in 34 participants (3.6 %) lesions had
      increased at least 25 % in diameter (mean increment 6.2 mm, range 2 - 15 mm).
      Subepithelial tumors with overlying mucosal changes (hyperemia, erosion, or
      ulcer) had a significantly higher risk of increasing in size (odds ratio [OR] =
      3.61, 95 % confidence interval [95 %CI] 1.06 - 12.28). Growth rates (size
      increment per year) for enlarging lesions were significantly correlated with
      initial size (r = 0.44, P = 0.009). CONCLUSIONS: Most incidentally detected small
      subepithelial tumors in the upper gastrointestinal tract showed no size change
      during follow-up. Thus, regular follow-up with serial endoscopy may be sufficient
      for small subepithelial tumors (< 2 cm) with intact overlying mucosa.

PMID- 25961445
TI  - Small pulmonary artery defects are not reliable indicators of pulmonary embolism.
AB  - OBJECTIVES: To evaluate the rate of agreement of pulmonary embolism diagnosis in
      computed tomography (CT) pulmonary angiogram studies and to evaluate the rate of
      inaccurate interpretations in the community hospital setting. METHODS: Using the
      keywords "pulmonary embolism/embolus/emboli," the radiology information system
      was searched for CT pulmonary angiograms performed over a 3-year period at three
      U.S. community hospitals. Studies containing probable or definite pulmonary
      emboli were independently reviewed by four subspecialty thoracic radiologists.
      MEASUREMENTS AND MAIN RESULTS: Agreement about the presence of pulmonary embolism
      progressively decreased with decreasing diameter of pulmonary vascular lesions (P
      < 0.0001). There was a sharp fall in observer agreement for pulmonary embolism of
      subsegmental lesions (P < 0.0001). The frequency of agreement decreased with
      decreasing quality of the imaging examination (P < 0.0001). Community
      radiologists were prone to false-positive pulmonary embolism diagnosis of
      subsegmental and/or small pulmonary arterial defects. The probability of a false
      positive diagnosis and indeterminate examinations progressively increased with:
      (1) more peripheral location of the lesion, (2) decreased size (short-axis
      diameter) of the lesion, and (3) diminishing quality of the CT examination. Forty
      eight of 177 (27%) of subsegmental vascular defects identified by community
      radiologists were deemed indeterminate, and 27 of 177 (15%) of subsegmental
      vascular defects were judged to be false positive for pulmonary embolism by the
      consensus diagnosis. Fifty-four of 274 (20%) vascular defects with short axis
      less than 6 mm were indeterminate for pulmonary embolism, and 37 of 274 (14%) of
      vascular defects with short axis less than 6 mm were false positive for pulmonary
      embolism. Eleven of 13 (85%) of vascular lesions identified as pulmonary emboli
      on the lowest-quality CT examinations were false positive or indeterminate for
      pulmonary embolism. False-positive examinations were most often due to
      respiratory motion artifact (19/38, 50%). CONCLUSIONS: There is relatively poor
      interobserver agreement for subsegmental and/or small pulmonary artery defects,
      especially in CT pulmonary angiograms degraded by technical artifacts. These
      factors can lead to an increased frequency of inaccurate interpretation or
      indeterminate diagnosis of subsegmental and/or small defects. Caution is
      indicated in interpreting the significance of small vascular defects in CT
      pulmonary angiograms.

PMID- 25961446
TI  - Hypoglycemic Accuracy and Improved Low Glucose Alerts of the Latest Dexcom G4
      Platinum Continuous Glucose Monitoring System.
AB  - OBJECTIVE: Accuracy of continuous glucose monitoring (CGM) devices in
      hypoglycemia has been a widely reported shortcoming of this technology. We report
      the accuracy in hypoglycemia of a new version of the Dexcom (San Diego, CA) G4
      Platinum CGM system (software 505) and present results regarding the optimum
      setting of CGM hypoglycemic alerts. MATERIALS AND METHODS: CGM values were
      compared with YSI analyzer (YSI Life Sciences, Yellow Springs, OH) measurements
      every 15 min. We reviewed the accuracy of the CGM system in the hypoglycemic
      range using standard metrics. We analyzed the time required for the CGM system to
      detect biochemical hypoglycemia (70 mg/dL) compared with the YSI with alert
      settings at 70 mg/dL and 80 mg/dL. We also analyzed the time between the YSI
      value crossing 55 mg/dL, defined as the threshold for cognitive impairment due to
      hypoglycemia, and when the CGM system alerted for hypoglycemia. RESULTS: The mean
      absolute difference for a glucose level of less than 70 mg/dL was 6 mg/dL. Ninety
      six percent of CGM values were within 20 mg/dL of the YSI values between 40 and
      80 mg/dL. When the CGM hypoglycemic alert was set at 80 mg/dL, the device
      provided an alert for biochemical hypoglycemia within 10 min in 95% of instances
      and at least a 10-min advance warning before the cognitive impairment threshold
      in 91% of instances in the study. CONCLUSIONS: Use of an 80 mg/dL threshold
      setting for hypoglycemic alerts on the G4 Platinum (software 505) may provide
      patients with timely warning of hypoglycemia before the onset of cognitive
      impairment, enabling them to treat themselves for hypoglycemia with fast-acting
      carbohydrates and prevent neuroglycopenia associated with very low glucose
      levels.

PMID- 25961447
TI  - Recommendations to Improve Employee Thermal Comfort When Working in 40 degrees F
      Refrigerated Cold Rooms.
AB  - Cold rooms are commonly used for food storage and preparation, and are usually
      kept around 40 degrees F following food safety guidelines. Some food preparation
      employees may spend 8 or more hours inside cold rooms. These employees may not be
      aware of the risks associated with mildly cold temperatures, dampness, and
      limited ventilation. We performed an evaluation of cold rooms at an airline
      catering facility because of concerns with exposure to cold temperatures. We
      spoke with and observed employees in two cold rooms, reviewed daily temperature
      logs, evaluated employee's physical activity, work/rest schedule, and protective
      clothing. We measured temperature, percent relative humidity, and air velocities
      at different work stations inside the cold rooms. We concluded that thermal
      comfort concerns perceived by cold room employees may have been the result of air
      drafts at their workstations, insufficient use of personal protective equipment
      due to dexterity concerns, work practices, and lack of knowledge about good
      health and safety practices in cold rooms. These moderately cold work conditions
      with low air velocities are not well covered in current occupational health and
      safety guidelines, and wind chill calculations do not apply. We provide practical
      recommendations to improve thermal comfort of cold room employees. Engineering
      control recommendations include the redesigning of air deflectors and installing
      of suspended baffles. Administrative controls include the changing out of wet
      clothing, providing hand warmers outside of cold rooms, and educating employees
      on cold stress. We also recommended providing more options on personal protective
      equipment. However, there is a need for guidelines and educational materials
      tailored to employees in moderately cold environments to improve thermal comfort
      and minimize health and safety problems. 

PMID- 25961448
TI  - Motivational Profiles for Physical Activity Practice in Adults with Type 2
      Diabetes: A Self-Determination Theory Perspective.
AB  - Drawing on Self-Determination Theory, this study explored the motivational
      profiles toward Physical Activity (PA) among adults with type 2 diabetes and the
      relationships between motivational profile, perceived competence and PA.
      Participants were 350 men and women (Mean age 62.77 years) who were interviewed
      on their motivations toward PA, perceived level of competence to practice, and PA
      practice. Cluster analyses reveal the existence of three distinct profiles: "High
      Combined" (ie, high scores on motivations ranging from intrinsic to external
      regulation, moderate level on amotivation), "Self-Determined" (ie, high scores on
      intrinsic, integrated, and identified regulations; low scores on other
      regulations), and "Moderate" (ie, moderate scores on all regulations).
      Participants with "High Combined" and "Self-Determined" profiles reported higher
      perceived competence and longer leisure-time PA practice in comparison to those
      with a "Moderate" profile. This study highlights the necessity of adopting a
      person-centered approach to better understand motivation toward PA among type 2
      diabetics.

PMID- 25961449
TI  - Tumor suppressor p53 stole the AKT in hypoxia.
AB  - The presence of hypoxia within a tumor is associated with poor clinical outcome,
      which is often exacerbated by loss of the tumor suppressor p53. In the presence
      of functional p53, hypoxic conditions promote apoptosis; however, the p53
      dependent genes that mediate this process are not well understood. In this issue
      of the JCI, Leszczynska and colleagues identify a p53-dependent six-gene
      signature that is specifically induced in hypoxia and mediates apoptosis. In
      patients with a variety of cancers, downregulation of this gene signature was
      associated with poor clinical outcome. Induction of p53-dependent apoptosis under
      hypoxia was mediated by AKT inhibition, and treatment with the combination of an
      AKT inhibitor and ionizing radiation decreased tumor size in a p53-deficient
      xenograft model more substantially than either single-agent treatment. The
      results of this study provide important insight into p53-mediated apoptosis under
      hypoxia and suggest that AKT inhibition has therapeutic potential for inducing
      apoptosis in hypoxic, p53-deficient cancers. 

PMID- 25961451
TI  - Embryonic stem cells as sources of donor-independent platelets.
AB  - The creation of a donor-independent source of platelets has been challenging;
      however, recent advances show growing promise for alternative platelet sources.
      Pluripotent stem cells have the capacity to differentiate into mature
      megakaryocytes with the ability to produce functional platelets. In this issue of
      JCI, Noh et al. provide a proof-of-principle demonstration that embryonic stem
      cells can be used to produce platelets on a clinical scale by controlling the
      level of the transcription factor GATA1. This study emphasizes the importance of
      precise regulation of gene expression for regenerative medicine applications. 

PMID- 25961450
TI  - T cell signaling abnormalities contribute to aberrant immune cell function and
      autoimmunity.
AB  - Systemic lupus erythematosus (SLE) is a prototype systemic autoimmune disease
      that results from a break in immune tolerance to self-antigens, leading to multi
      organ destruction. Autoantibody deposition and inflammatory cell infiltration in
      target organs such as kidneys and brain lead to complications of this disease.
      Dysregulation of cellular and humoral immune response elements, along with organ
      defined molecular aberrations, form the basis of SLE pathogenesis. Aberrant T
      lymphocyte activation due to signaling abnormalities, linked to defective gene
      transcription and altered cytokine production, are important contributors to SLE
      pathophysiology. A better understanding of signaling and gene regulation defects
      in SLE T cells will lead to the identification of specific novel molecular
      targets and predictive biomarkers for therapy. 

PMID- 25961452
TI  - Pouring fuel on the fire: Th17 cells, the environment, and autoimmunity.
AB  - Cytokines play a critical role in controlling the differentiation of CD4 Th cells
      into distinct subsets, including IL-17-producing Th17 cells. Unfortunately, the
      incidence of a number of autoimmune diseases, particularly those in which the IL
      23/IL-17 axis has been implicated, has risen in the last several decades,
      suggesting that environmental factors can promote autoimmunity. Here we review
      the role of cytokines in Th17 differentiation, particularly the role of IL-23 in
      promoting the differentiation of a pathogenic subset of Th17 cells that potently
      induce autoimmune tissue inflammation. Moreover, we highlight emerging data that
      indicate that environmental factors, including the intestinal microbiota and
      changes in diet, can alter normal cytokine regulation with potent effects on Th17
      differentiation and thus promote autoimmunity, which has strong implications for
      human disease. 

PMID- 25961454
TI  - Inducible Gata1 suppression expands megakaryocyte-erythroid progenitors from
      embryonic stem cells.
AB  - Transfusion of donor-derived platelets is commonly used for thrombocytopenia,
      which results from a variety of clinical conditions and relies on a constant
      donor supply due to the limited shelf life of these cells. Embryonic stem (ES)
      and induced pluripotent stem (iPS) cells represent a potential source of
      megakaryocytes and platelets for transfusion therapies; however, the majority of
      current ES/iPS cell differentiation protocols are limited by low yields of
      hematopoietic progeny. In both mice and humans, mutations in the gene-encoding
      transcription factor GATA1 cause an accumulation of proliferating,
      developmentally arrested megakaryocytes, suggesting that GATA1 suppression in ES
      and iPS cell-derived hematopoietic progenitors may enhance megakaryocyte
      production. Here, we engineered ES cells from WT mice to express a doxycycline
      regulated (dox-regulated) shRNA that targets Gata1 transcripts for degradation.
      Differentiation of these cells in the presence of dox and thrombopoietin (TPO)
      resulted in an exponential (at least 1013-fold) expansion of immature
      hematopoietic progenitors. Dox withdrawal in combination with multilineage
      cytokines restored GATA1 expression, resulting in differentiation into
      erythroblasts and megakaryocytes. Following transfusion into recipient animals,
      these dox-deprived mature megakaryocytes generated functional platelets. Our
      findings provide a readily reproducible strategy to exponentially expand ES cell
      derived megakaryocyte-erythroid progenitors that have the capacity to
      differentiate into functional platelet-producing megakaryocytes.

PMID- 25961453
TI  - Bacterial induction of Snail1 contributes to blood-brain barrier disruption.
AB  - Bacterial meningitis is a serious infection of the CNS that results when blood
      borne bacteria are able to cross the blood-brain barrier (BBB). Group B
      Streptococcus (GBS) is the leading cause of neonatal meningitis; however, the
      molecular mechanisms that regulate bacterial BBB disruption and penetration are
      not well understood. Here, we found that infection of human brain microvascular
      endothelial cells (hBMECs) with GBS and other meningeal pathogens results in the
      induction of host transcriptional repressor Snail1, which impedes expression of
      tight junction genes. Moreover, GBS infection also induced Snail1 expression in
      murine and zebrafish models. Tight junction components ZO-1, claudin 5, and
      occludin were decreased at both the transcript and protein levels in hBMECs
      following GBS infection, and this repression was dependent on Snail1 induction.
      Bacteria-independent Snail1 expression was sufficient to facilitate tight
      junction disruption, promoting BBB permeability to allow bacterial passage. GBS
      induction of Snail1 expression was dependent on the ERK1/2/MAPK signaling cascade
      and bacterial cell wall components. Finally, overexpression of a dominant
      negative Snail1 homolog in zebrafish elevated transcription of tight junction
      protein-encoding genes and increased zebrafish survival in response to GBS
      challenge. Taken together, our data support a Snail1-dependent mechanism of BBB
      disruption and penetration by meningeal pathogens. 

PMID- 25961455
TI  - Hypoxia-induced p53 modulates both apoptosis and radiosensitivity via AKT.
AB  - Restoration of hypoxia-induced apoptosis in tumors harboring p53 mutations has
      been proposed as a potential therapeutic strategy; however, the transcriptional
      targets that mediate hypoxia-induced p53-dependent apoptosis remain elusive.
      Here, we demonstrated that hypoxia-induced p53-dependent apoptosis is reliant on
      the DNA-binding and transactivation domains of p53 but not on the acetylation
      sites K120 and K164, which, in contrast, are essential for DNA damage-induced,
      p53-dependent apoptosis. Evaluation of hypoxia-induced transcripts in multiple
      cell lines identified a group of genes that are hypoxia-inducible proapoptotic
      targets of p53, including inositol polyphosphate-5-phosphatase (INPP5D),
      pleckstrin domain-containing A3 (PHLDA3), sulfatase 2 (SULF2), B cell
      translocation gene 2 (BTG2), cytoplasmic FMR1-interacting protein 2 (CYFIP2), and
      KN motif and ankyrin repeat domains 3 (KANK3). These targets were also regulated
      by p53 in human cancers, including breast, brain, colorectal, kidney, bladder,
      and melanoma cancers. Downregulation of these hypoxia-inducible targets
      associated with poor prognosis, suggesting that hypoxia-induced apoptosis
      contributes to p53-mediated tumor suppression and treatment response. Induction
      of p53 targets, PHLDA3, and a specific INPP5D transcript mediated apoptosis in
      response to hypoxia through AKT inhibition. Moreover, pharmacological inhibition
      of AKT led to apoptosis in the hypoxic regions of p53-deficient tumors and
      consequently increased radiosensitivity. Together, these results identify
      mediators of hypoxia-induced p53-dependent apoptosis and suggest AKT inhibition
      may improve radiotherapy response in p53-deficient tumors. 

PMID- 25961458
TI  - Human prion protein sequence elements impede cross-species chronic wasting
      disease transmission.

PMID- 25961456
TI  - Notch promotes recurrence of dormant tumor cells following HER2/neu-targeted
      therapy.
AB  - Breast cancer mortality is principally due to recurrent tumors that arise from a
      reservoir of residual tumor cells that survive therapy. Remarkably, breast
      cancers can recur after extended periods of clinical remission, implying that at
      least some residual tumor cells pass through a dormant phase prior to relapse.
      Nevertheless, the mechanisms that contribute to breast cancer recurrence are
      poorly understood. Using a mouse model of recurrent mammary tumorigenesis in
      combination with bioinformatics analyses of breast cancer patients, we have
      identified a role for Notch signaling in mammary tumor dormancy and recurrence.
      Specifically, we found that Notch signaling is acutely upregulated in tumor cells
      following HER2/neu pathway inhibition, that Notch signaling remains activated in
      a subset of dormant residual tumor cells that persist following HER2/neu
      downregulation, that activation of Notch signaling accelerates tumor recurrence,
      and that inhibition of Notch signaling by either genetic or pharmacological
      approaches impairs recurrence in mice. Consistent with these findings, meta
      analysis of microarray data from over 4,000 breast cancer patients revealed that
      elevated Notch pathway activity is independently associated with an increased
      rate of recurrence. Together, these results implicate Notch signaling in tumor
      recurrence from dormant residual tumor cells and provide evidence that dormancy
      is a targetable stage of breast cancer progression. 

PMID- 25961457
TI  - KANK deficiency leads to podocyte dysfunction and nephrotic syndrome.
AB  - Steroid-resistant nephrotic syndrome (SRNS) is a frequent cause of progressive
      renal function decline and affects millions of people. In a recent study, 30% of
      SRNS cases evaluated were the result of monogenic mutations in 1 of 27 different
      genes. Here, using homozygosity mapping and whole-exome sequencing, we identified
      recessive mutations in kidney ankyrin repeat-containing protein 1 (KANK1), KANK2,
      and KANK4 in individuals with nephrotic syndrome. In an independent functional
      genetic screen of Drosophila cardiac nephrocytes, which are equivalents of
      mammalian podocytes, we determined that the Drosophila KANK homolog (dKank) is
      essential for nephrocyte function. RNAi-mediated knockdown of dKank in
      nephrocytes disrupted slit diaphragm filtration structures and lacuna channel
      structures. In rats, KANK1, KANK2, and KANK4 all localized to podocytes in
      glomeruli, and KANK1 partially colocalized with synaptopodin. Knockdown of kank2
      in zebrafish recapitulated a nephrotic syndrome phenotype, resulting in
      proteinuria and podocyte foot process effacement. In rat glomeruli and cultured
      human podocytes, KANK2 interacted with ARHGDIA, a known regulator of RHO GTPases
      in podocytes that is dysfunctional in some types of nephrotic syndrome. Knockdown
      of KANK2 in cultured podocytes increased active GTP-bound RHOA and decreased
      migration. Together, these data suggest that KANK family genes play
      evolutionarily conserved roles in podocyte function, likely through regulating
      RHO GTPase signaling. 

PMID- 25961459
TI  - Macrophage migration inhibitory factor promotes cyst growth in polycystic kidney
      disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is characterized by renal
      cyst formation, inflammation, and fibrosis. Macrophages infiltrate cystic
      kidneys, but the role of these and other inflammatory factors in disease
      progression are poorly understood. Here, we identified macrophage migration
      inhibitory factor (MIF) as an important regulator of cyst growth in ADPKD. MIF
      was upregulated in cyst-lining epithelial cells in polycystin-1-deficient murine
      kidneys and accumulated in cyst fluid of human ADPKD kidneys. MIF promoted cystic
      epithelial cell proliferation by activating ERK, mTOR, and Rb/E2F pathways and by
      increasing glucose uptake and ATP production, which inhibited AMP-activated
      protein kinase signaling. MIF also regulated cystic renal epithelial cell
      apoptosis through p53-dependent signaling. In polycystin-1-deficient mice, MIF
      was required for recruitment and retention of renal macrophages, which promoted
      cyst expansion, and Mif deletion or pharmacologic inhibition delayed cyst growth
      in multiple murine ADPKD models. MIF-dependent macrophage recruitment was
      associated with upregulation of monocyte chemotactic protein 1 (MCP-1) and
      inflammatory cytokine TNF-alpha. TNF-alpha induced MIF expression, and MIF
      subsequently exacerbated TNF-alpha expression in renal epithelial cells,
      suggesting a positive feedback loop between TNF-alpha and MIF during cyst
      development. Our study indicates MIF is a central and upstream regulator of ADPKD
      pathogenesis and provides a rationale for further exploration of MIF as a
      therapeutic target for ADPKD. 

PMID- 25961460
TI  - MicroRNA-26a regulates insulin sensitivity and metabolism of glucose and lipids.
AB  - Type 2 diabetes (T2D) is characterized by insulin resistance and increased
      hepatic glucose production, yet the molecular mechanisms underlying these
      abnormalities are poorly understood. MicroRNAs (miRs) are a class of small,
      noncoding RNAs that have been implicated in the regulation of human diseases,
      including T2D. miR-26a is known to play a critical role in tumorigenesis;
      however, its function in cellular metabolism remains unknown. Here, we determined
      that miR-26a regulates insulin signaling and metabolism of glucose and lipids.
      Compared with lean individuals, overweight humans had decreased expression of miR
      26a in the liver. Moreover, miR-26 was downregulated in 2 obese mouse models
      compared with control animals. Global or liver-specific overexpression of miR-26a
      in mice fed a high-fat diet improved insulin sensitivity, decreased hepatic
      glucose production, and decreased fatty acid synthesis, thereby preventing
      obesity-induced metabolic complications. Conversely, silencing of endogenous miR
      26a in conventional diet-fed mice impaired insulin sensitivity, enhanced glucose
      production, and increased fatty acid synthesis. miR-26a targeted several key
      regulators of hepatic metabolism and insulin signaling. These findings reveal miR
      26a as a regulator of liver metabolism and suggest miR-26a should be further
      explored as a potential target for the treatment of T2D. 

PMID- 25961461
TI  - Anacetrapib lowers LDL by increasing ApoB clearance in mildly
      hypercholesterolemic subjects.
AB  - BACKGROUND: Individuals treated with the cholesteryl ester transfer protein
      (CETP) inhibitor anacetrapib exhibit a reduction in both LDL cholesterol and
      apolipoprotein B (ApoB) in response to monotherapy or combination therapy with a
      statin. It is not clear how anacetrapib exerts these effects; therefore, the goal
      of this study was to determine the kinetic mechanism responsible for the
      reduction in LDL and ApoB in response to anacetrapib. METHODS: We performed a
      trial of the effects of anacetrapib on ApoB kinetics. Mildly hypercholesterolemic
      subjects were randomized to background treatment of either placebo (n = 10) or 20
      mg atorvastatin (ATV) (n = 29) for 4 weeks. All subjects then added 100 mg
      anacetrapib to background treatment for 8 weeks. Following each study period,
      subjects underwent a metabolic study to determine the LDL-ApoB-100 and proprotein
      convertase subtilisin/kexin type 9 (PCSK9) production rate (PR) and fractional
      catabolic rate (FCR). RESULTS: Anacetrapib markedly reduced the LDL-ApoB-100 pool
      size (PS) in both the placebo and ATV groups. These changes in PS resulted from
      substantial increases in LDL-ApoB-100 FCRs in both groups. Anacetrapib had no
      effect on LDL-ApoB-100 PRs in either treatment group. Moreover, there were no
      changes in the PCSK9 PS, FCR, or PR in either group. Anacetrapib treatment was
      associated with considerable increases in the LDL triglyceride/cholesterol ratio
      and LDL size by NMR. CONCLUSION: These data indicate that anacetrapib, given
      alone or in combination with a statin, reduces LDL-ApoB-100 levels by increasing
      the rate of ApoB-100 fractional clearance. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00990808. FUNDING: Merck & Co. Inc., Kenilworth, New Jersey, USA. Additional
      support for instrumentation was obtained from the National Center for Advancing
      Translational Sciences (UL1TR000003 and UL1TR000040).

PMID- 25961462
TI  - Mental health problems of undocumented migrants in the Netherlands: A qualitative
      exploration of recognition, recording, and treatment by general practitioners.
AB  - OBJECTIVE: To explore the views and experiences of general practitioners (GPs) in
      relation to recognition, recording, and treatment of mental health problems of
      undocumented migrants (UMs), and to gain insight in the reasons for under
      registration of mental health problems in the electronic medical records. DESIGN:
      Qualitative study design with semi-structured interviews using a topic guide.
      SUBJECTS AND SETTING: Sixteen GPs in the Netherlands with clinical expertise in
      the care of UMs. RESULTS: GPs recognized many mental health problems in UMs.
      Barriers that prevented them from recording these problems and from delivering
      appropriate care were their low consultation rates, physical presentation of
      mental health problems, high number of other problems, the UM's lack of trust
      towards health care professionals, and cultural differences in health beliefs and
      language barriers. Referrals to mental health care organizations were often seen
      as problematic by GPs. To overcome these barriers, GPs provided personalized care
      as far as possible, referred to other primary care professionals such as social
      workers or mental health care nurses in their practice, and were a little less
      restrictive in prescribing psychotropics than guidelines recommended.
      CONCLUSIONS: GPs experienced a variety of barriers in engaging with UMs when
      identifying or suspecting mental health problems. This explains why there is a
      gap between the high recognition of mental health problems and the low recording
      of these problems in general practice files. It is recommended that GPs address
      mental health problems more actively, strive for continuity of care in order to
      gain trust of the UMs, and look for opportunities to provide mental care that is
      accessible and acceptable for UMs.

PMID- 25961463
TI  - Anti-Diabetic Effect of Aster sphathulifolius in C57BL/KsJ-db/db Mice.
AB  - In this study, we investigated the anti-diabetic effect of Aster sphathulifolius
      (AS) extract in C57BL/KsJ-db/db mice. The db/db mice were orally administered
      with AS 50% ethanol extract at concentrations of 50, 100, and 200 mg/kg/day
      (db/db-AS50, db/db-AS100, and db/db-AS200, respectively) for 10 weeks. Food and
      water intake, fasting blood glucose concentrations, blood glycosylated hemoglobin
      levels, and plasma insulin levels were significantly lower in the db/db-AS200
      group than in the vehicle-treated db/db group; whereas glucose tolerance was
      significantly improved in the db/db-AS200 group. Moreover, AS dose dependently
      increased both insulin receptor substrate 1 and glucose transporter type 4
      expression in skeletal muscle, significantly increased glucokinase expression,
      and decreased glucose 6-phosphatase and phosphoenolpyruvate carboxykinase
      expressions in the liver. The expressions of transcription factors, such as
      sterol-regulatory element-binding protein, peroxisome proliferator-activated
      receptor gamma, and adipocyte protein 2, were upregulated in adipose tissue.
      Furthermore, immunohistochemical analysis showed that AS upregulated insulin
      production by increasing pancreatic beta-cell mass. In summary, AS extract
      normalized hyperglycemia by multiple mechanisms: inhibition of glyconeogenesis,
      acceleration of glucose metabolism and lipid metabolism, and increase of glucose
      uptake. Using in vivo assays, this study has shown the potential of AS as a
      medicinal food and suggests the efficacy of AS for the use of prevention of
      diabetes.

PMID- 25961464
TI  - Estrogen withdrawal, increased breast cancer risk and the KRAS-variant.
AB  - The KRAS-variant is a biologically functional, microRNA binding site variant,
      which predicts increased cancer risk especially for women. Because external
      exposures, such as chemotherapy, differentially impact the effect of this
      mutation, we evaluated the association of estrogen exposures, breast cancer (BC)
      risk and tumor biology in women with the KRAS-variant. Women with BC (n = 1712),
      the subset with the KRAS-variant (n = 286) and KRAS-variant unaffected controls
      (n = 80) were evaluated, and hormonal exposures, KRAS-variant status, and
      pathology were compared. The impact of estrogen withdrawal on transformation of
      isogenic normal breast cell lines with or without the KRAS-variant was studied.
      Finally, the association and presentation characteristics of the KRAS-variant and
      multiple primary breast cancer (MPBC) were evaluated. KRAS-variant BC patients
      were more likely to have ovarian removal pre-BC diagnosis than non-variant BC
      patients (p = 0.033). In addition, KRAS-variant BC patients also appeared to have
      a lower estrogen state than KRAS-variant unaffected controls, with a lower BMI (P
      < 0.001). Finally, hormone replacement therapy (HRT) discontinuation in KRAS
      variant patients was associated with a diagnosis of triple negative BC (P <
      0.001). Biologically confirming our clinical findings, acute estrogen withdrawal
      led to oncogenic transformation in KRAS-variant positive isogenic cell lines.
      Finally, KRAS-variant BC patients had greater than an 11-fold increased risk of
      presenting with MPBC compared to non-variant patients (45.39% vs 6.78%, OR 11.44
      [3.42-37.87], P < 0.001). Thus, estrogen withdrawal and a low estrogen state
      appear to increase BC risk and to predict aggressive tumor biology in women with
      the KRAS-variant, who are also significantly more likely to present with multiple
      primary breast cancer.

PMID- 25961465
TI  - Valid screening questions useful to diagnose hand and forearm eczema are
      available in the Spanish language, a new tool for global research.
AB  - Hand eczema is an impacting cutaneous disease. Globally valid tools that help to
      diagnose hand and forearm eczema are required. OBJECTIVE: To validate the
      questions to detect hand and/or forearm eczema included in the "Nordic
      Occupational Skin Questionnaire" (NOSQ-2002) in the Spanish language. MATERIALS
      AND METHODS: A prospective pilot study was conducted with 80 employees of a
      cleaning company and a retrospective one involving 2,546 individuals. The
      responses were analysed for sensitivity, specificity and positive and negative
      predictive values. The final diagnosis according to the patients' hospital
      records, the specialty care records and the physical examination was taken as
      gold standard. The Dermatology Life Quality Index (DLQI) was also evaluated.
      RESULTS: Sensitivity and specificity, in a worst case scenario (WC) combining
      both questions, were 96.5% and 66.7%, respectively, and in a per protocol (PP)
      analysis, were 96.5% and 75.2%. CONCLUSION: The questions validated detected
      eczema effectively, making this tool suitable for use e.g. in multicentre
      epidemiological studies or clinical trials.

PMID- 25961468
TI  - An appraisal theory of empathy and other vicarious emotional experiences.
AB  - Empathy, feeling what others feel, is regarded as a special phenomenon that is
      separate from other emotional experiences. Emotion theories say little about
      feeling emotions for others and empathy theories say little about how feeling
      emotions for others relates to normal firsthand emotional experience. Current
      empathy theories focus on how we feel emotions for others who feel the same
      thing, but not how we feel emotions for others that they do not feel, such as
      feeling angry for someone who is sad or feeling embarrassed for someone who is
      self-assured. We propose an appraisal theory of vicarious emotional experiences,
      including empathy, based on appraisal theories of emotion. According to this
      theory, emotions for others are based on how we evaluate their situations, just
      as firsthand emotions are based on how we evaluate our own situations. We discuss
      how this framework can predict empathic emotion matching and also the experience
      of emotions for others that do not match what they feel. The theory treats
      empathy as a normal part of emotional experience.

PMID- 25961466
TI  - Regulation and function of P-Rex family Rac-GEFs.
AB  - The P-Rex family are Dbl-type guanine-nucleotide exchange factors for Rac family
      small G proteins. They are distinguished from other Rac-GEFs through their
      synergistic mode of activation by the lipid second messenger phosphatidyl
      inositol (3,4,5) trisphosphate and the Gbetagamma subunits of heterotrimeric G
      proteins, thus acting as coincidence detectors for phosphoinositide 3-kinase and
      G protein coupled receptor signaling. Work in genetically-modified mice has shown
      that P-Rex1 has physiological importance in the inflammatory response and the
      migration of melanoblasts during development, whereas P-Rex2 controls the
      dendrite morphology of cerebellar Purkinje neurons as well as glucose homeostasis
      in liver and adipose tissue. Deregulation of P-Rex1 and P-Rex2 expression occurs
      in many types of cancer, and P-Rex2 is frequently mutated in melanoma. Both GEFs
      promote tumor growth or metastasis. This review critically evaluates the P-Rex
      literature and tools available and highlights exciting recent developments and
      open questions. 

PMID- 25961469
TI  - Generating structure from experience: A retrieval-based model of language
      processing.
AB  - Standard theories of language generally assume that some abstraction of
      linguistic input is necessary to create higher level representations of
      linguistic structures (e.g., a grammar). However, the importance of individual
      experiences with language has recently been emphasized by both usage-based
      theories (Tomasello, 2003) and grounded and situated theories (e.g., Zwaan &
      Madden, 2005). Following the usage-based approach, we present a formal exemplar
      model that stores instances of sentences across a natural language corpus,
      applying recent advances from models of semantic memory. In this model, an
      exemplar memory is used to generate expectations about the future structure of
      sentences, using a mechanism for prediction in language processing (Altmann &
      Mirkovic, 2009). The model successfully captures a broad range of behavioral
      effects-reduced relative clause processing (Reali & Christiansen, 2007), the role
      of contextual constraint (Rayner & Well, 1996), and event knowledge activation
      (Ferretti, Kutas, & McRae, 2007), among others. We further demonstrate how
      perceptual knowledge could be integrated into this exemplar-based framework, with
      the goal of grounding language processing in perception. Finally, we illustrate
      how an exemplar memory system could have been used in the cultural evolution of
      language. The model provides evidence that an impressive amount of language
      processing may be bottom-up in nature, built on the storage and retrieval of
      individual linguistic experiences.

PMID- 25961467
TI  - A risk and maintenance model for bulimia nervosa: From impulsive action to
      compulsive behavior.
AB  - This article offers a new model for bulimia nervosa (BN) that explains both the
      initial impulsive nature of binge eating and purging, as well as the compulsive
      quality of the fully developed disorder. The model is based on a review of
      advances in research on BN and advances in relevant basic psychological science.
      It integrates transdiagnostic personality risk, eating-disorder-specific risk,
      reinforcement theory, cognitive neuroscience, and theory drawn from the drug
      addiction literature. We identify both a state-based and a trait-based risk
      pathway, and we then propose possible state-by-trait interaction risk processes.
      The state-based pathway emphasizes depletion of self-control. The trait-based
      pathway emphasizes transactions between the trait of negative urgency (the
      tendency to act rashly when distressed) and high-risk psychosocial learning. We
      then describe a process by which initially impulsive BN behaviors become
      compulsive over time, and we consider the clinical implications of our model.
      (PsycINFO Database Record 

PMID- 25961472
TI  - Airway microbiota and acute respiratory infection in children.
AB  - Acute respiratory infections (ARIs), such as bronchiolitis and pneumonia, are the
      leading cause of hospitalization of infants in the US. While the incidence and
      severity of ARI can vary widely among children, the reasons for these differences
      are not fully explained by traditional risk factors (e.g., prematurity, viral
      pathogens). The recent advent of molecular diagnostic techniques has revealed the
      presence of highly functional communities of microbes inhabiting the human body
      (i.e., microbiota) that appear to influence development of local and systemic
      immune response. We propose a 'risk and resilience' model in which airway
      microbiota are associated with an increased (risk microbiota) or decreased
      (resilience microbiota) incidence and severity of ARI in children. We also
      propose that modulating airway microbiota (e.g., from risk to resilience
      microbiota) during early childhood will optimize airway immunity and, thereby,
      decrease ARI incidence and severity in children. 

PMID- 25961471
TI  - Delayed Methylene Blue Improves Lesion Volume, Multi-Parametric Quantitative
      Magnetic Resonance Imaging Measurements, and Behavioral Outcome after Traumatic
      Brain Injury.
AB  - Traumatic brain injury (TBI) remains a primary cause of death and disability in
      both civilian and military populations worldwide. There is a critical need for
      the development of neuroprotective agents that can circumvent damage and provide
      functional recovery. We previously showed that methylene blue (MB), a U.S. Food
      and Drug Administration-grandfathered drug with energy-enhancing and antioxidant
      properties, given 1 and 3 h post-TBI, had neuroprotective effects in rats. This
      study aimed to further investigate the neuroprotection of delayed MB treatment
      (24 h postinjury) post-TBI as measured by lesion volume and functional outcomes.
      Comparisons were made with vehicle and acute MB treatment. Multi-modal magnetic
      resonance imaging and behavioral studies were performed at 1 and 3 h and 2, 7,
      and 14 days after an impact to the primary forelimb somatosensory cortex. We
      found that delaying MB treatment 24 h postinjury still minimized lesion volume
      and functional deficits, compared to vehicle-treated animals. The data further
      support the potential for MB as a neuroprotective treatment, especially when
      medical teatment is not readily available. MB has an excellent safety profile and
      is clinically approved for other indications. MB clinical trials on TBI can thus
      be readily explored. 

PMID- 25961473
TI  - Conformation-Dependent Human p52Shc Phosphorylation by Human c-Src.
AB  - Phosphorylation of the human p52Shc adaptor protein is a key determinant in
      modulating signaling complex assembly in response to tyrosine kinase signaling
      cascade activation. The underlying mechanisms that govern p52Shc phosphorylation
      status are unknown. In this study, p52Shc phosphorylation by human c-Src was
      investigated using purified proteins to define mechanisms that affect the p52Shc
      phosphorylation state. We conducted biophysical characterizations of both human
      p52Shc and human c-Src in solution as well as membrane-mimetic environments using
      the acidic lipid phosphatidylinositol 4-phosphate or a novel amphipathic
      detergent (2,2-dihexylpropane-1,3-bis-beta-D-glucopyranoside). We then identified
      p52Shc phosphorylation sites under various solution conditions, and the amount of
      phosphorylation at each identified site was quantified using mass spectrometry.
      These data demonstrate that the p52Shc phosphorylation level is altered by the
      solution environment without affecting the fraction of active c-Src. Mass
      spectrometry analysis of phosphorylated p52Shc implies functional linkage among
      phosphorylation sites. This linkage may drive preferential coupling to protein
      binding partners during signaling complex formation, such as during initial
      binding interactions with the Grb2 adaptor protein leading to activation of the
      Ras/MAPK signaling cascade. Remarkably, tyrosine residues involved in Grb2
      binding were heavily phosphorylated in a membrane-mimetic environment. The
      increased phosphorylation level in Grb2 binding residues was also correlated with
      a decrease in the thermal stability of purified human p52Shc. A schematic for the
      phosphorylation-dependent interaction between p52Shc and Grb2 is proposed. The
      results of this study suggest another possible therapeutic strategy for altering
      protein phosphorylation to regulate signaling cascade activation.

PMID- 25961475
TI  - Trauma nurses: making a difference.

PMID- 25961474
TI  - Growing together.

PMID- 25961476
TI  - STN News and Notes.

PMID- 25961477
TI  - What we now know about the new oral anticoagulants and their reversal.

PMID- 25961479
TI  - Penetrating knitting needle through the mediastinum in a child.
AB  - Thoracic injuries are second only to central nervous system injuries as the
      leading cause of traumatic death in patients of all ages. Penetrating chest
      injury is very uncommon in children, but it comes with significant morbidity and
      mortality. Presentation of penetrating thoracic injury in the child is unique
      with inherent opportunities for learning. The purpose of this case report was to
      disseminate information regarding rare thoracic trauma in the pediatric patient. 

PMID- 25961478
TI  - Risk factors for ventilator-associated pneumonia: among trauma patients with and
      without brain injury.
AB  - Ventilator-associated pneumonia (VAP) rates remain highest among trauma and brain
      injured patients; yet, no research compares VAP risk factors between the 2
      groups. This retrospective, case-controlled study identified risk factors for VAP
      among critically ill trauma patients with and without brain injury. Data were
      abstracted on trauma patients with (cases) and without (controls) brain injury.
      Data gathered on n = 157 subjects. Trauma patients with brain injury had more
      emergent and field intubations. Age was strongest predictor of VAP in cases, and
      ventilator days predicted VAP in controls. Trauma patients with brain injury may
      be at higher risk for VAP. 

PMID- 25961480
TI  - Examining the relationship between preinjury health and injury-related factors to
      discharge location and risk for injury-associated complications in patients after
      blunt thoracic trauma: a pilot study.
AB  - OBJECTIVE: To determine whether preinjury health and injury-related factors were
      associated with posthospitalization discharge location and injury-associated
      complications for patients with blunt thoracic trauma. METHODS: A retrospective
      analysis using registry data from a level 1 trauma center was conducted. A random
      sample of 200 patients admitted between 2009 and 2012 was included. Relationships
      between variables were assessed through cross-tabulation with the chi-square
      analysis; a P value <.05 was considered statistically significant. RESULTS:
      Alcohol/drug use was related to hospital discharge location. Most patients with
      alcohol involved injuries discharged to locations other than home or long-term
      care facilities. Of the 59 patients who required intensive care, their length of
      stay was less than 3 days, and 24 required mechanical ventilation for short
      periods. Most blunt thoracic trauma patients were hospitalized less than 7 days.
      A relationship was identified between discharge location and the presence of any
      of the National Trauma Databank comorbid conditions and the comorbid condition of
      bleeding. A relationship between rib fractures and injury-associated
      complications was not found. The complication of pneumonia was related to length
      of stay and primary payment method. CONCLUSION: Comorbid medical conditions and
      injury-related factors were associated with injury-related complications and
      discharge location for select variables. Further exploration with is needed to
      elucidate the associations more fully.

PMID- 25961481
TI  - Bedside Tracheostomy and Percutaneous Endoscopic Gastrostomy on the Patient's
      Television.
AB  - Bedside surgical procedures such as percutaneous dilatational tracheostomy (PDT)
      and percutaneous endoscopic gastrostomy (PEG) placement in ICU settings are
      widely accepted; however, these procedures often require the addition of bulky
      equipment into the patient's room, which consumes valuable space and restrict
      workflow. A practice modification was developed in our trauma program, which
      reduces clutter in the patient's room, streamlines workflow, and results in
      better patient care and teaching. Simple and cost-effective, this has become the
      standard in our trauma center and could be of benefit to other institutions as
      well. 

PMID- 25961482
TI  - The role and impact of the specialist trauma nurse: an integrative review.
AB  - To identify the scope, context, and impact on patient and health service outcomes
      of the specialist trauma nurse. Integrative review with data sourced from CINAHL,
      OvidSP, Scopus, and hand searching of references. Abstracts were screened for
      inclusion/exclusion criteria with 56 articles appraised for quality, analyzed,
      and synthesized into 3 main categories. This international review shows a widely
      varied scope and context of practice with positive impacts on patient and health
      service outcomes. Further research and exploration are recommended to develop a
      consistent model of care and further ascertain the benefits of the specialist
      trauma nurse role. 

PMID- 25961483
TI  - Preventing secondary complications in trauma patients with implementation of a
      multidisciplinary mobilization team.
AB  - Management of the trauma patient is complex. Immobility or bed rest has
      detrimental effects on multiple body systems. Early mobilization, especially in
      the multi-injured patient, can be challenging requiring a multidisciplinary team
      effort. Health care team members' and patient's understanding and perceptions of
      bed rest greatly influence successful early mobilization. Integrating a
      multidisciplinary mobility program in the acute care setting can decrease
      secondary complications and hospital length of stay ultimately improving patient
      outcomes. Using the strategy for translating research into evidence based
      practice by incorporating the 4 "Es" of Engage, Educate, Execute, and Evaluate
      will assist in creating a culture of mobility. 

PMID- 25961484
TI  - Implementing a domestic violence screening program.
AB  - The purpose of this study was to design and implement a domestic violence (DV)
      screening protocol. Trauma patients meeting inclusion criteria (hospitalized > 48
      hours) were given a four question DV screen. If abuse was found, a comprehensive
      DV questionnaire followed. Barriers to screening and results were recorded.
      Compliance during the pilot test showed 23 of 157 (14.6%) admitted patients were
      screened. In the implementation year, 446 of 721 (61.9%) were screened. During
      the 10-month follow-up, 499 of 619 (80.6%) patients were screened. Lack of social
      work resources was the primary barrier to screening, but compliance increased and
      was maintained after the study period. 

PMID- 25961487
TI  - SCR atmosphere induced reduction of oxidized mercury over CuO-CeO2/TiO2 catalyst.
AB  - CuO-CeO2/TiO2 (CuCeTi) catalyst synthesized by a sol-gel method was employed to
      investigate mercury conversion under a selective catalytic reduction (SCR)
      atmosphere (NO, NH3 plus O2). Neither NO nor NH3 individually exhibited an
      inhibitive effect on elemental mercury (Hg(0)) conversion in the presence of O2.
      However, Hg(0) conversion over the CuCeTi catalyst was greatly inhibited under
      SCR atmosphere. Systematic experiments were designed to investigate the
      inconsistency and explore the in-depth mechanisms. The results show that the
      copresence of NO and NH3 induced reduction of oxidized mercury (Hg(2+), HgO in
      this study), which offset the effect of catalytic Hg(0) oxidation, and hence
      resulted in deactivation of Hg(0) conversion. High NO and NH3 concentrations with
      a NO/NH3 ratio of 1.0 facilitated Hg(2+) reduction and therefore lowered Hg(0)
      conversion. Hg(2+) reduction over the CuCeTi catalyst was proposed to follow two
      possible mechanisms: (1) direct reaction, in which NO and NH3 react directly with
      HgO to form N2 and Hg(0); (2) indirect reaction, in which the SCR reaction
      consumed active surface oxygen on the CuCeTi catalyst, and reduced species on the
      CuCeTi catalyst surface such as Cu2O and Ce2O3 robbed oxygen from adjacent HgO.
      Different from the conventionally considered mechanisms, that is, competitive
      adsorption responsible for deactivation of Hg(0) conversion, this study reveals
      that oxidized mercury can transform into Hg(0) under SCR atmosphere. Such
      knowledge is of fundamental importance in developing efficient and economical
      mercury control technologies for coal-fired power plants.

PMID- 25961490
TI  - Prominent HLA-G Expression in Liver Disease But Not After Liver Transplantation.
AB  - BACKGROUND: HLA-G is a nonclassical MHC class I molecule and its physiological
      expression restricted to placental extravillous trophoblasts contributes to
      maternal tolerance to the semiallogeneic fetus. Aberrant expression of HLA-G in
      human organ grafts has been proposed to contribute to graft acceptance. METHODS:
      We studied HLA-G expression in liver tissue and serum of adult liver transplant
      recipients before, early, and late after transplantation in relation to liver
      function and operational tolerance. RESULTS: Cirrhotic explant livers showed
      robust HLA-G expression on hepatocytes, whereas the majority of noncirrhotic
      livers and graft biopsies taken before or after liver transplantation (LTX)
      showed no, or weak, HLA-G expression. The HLA-G expression was induced on
      hepatocytes in vitro by TGF-beta, but not by other relevant cytokines. Serum
      levels of the HLA-G isoforms 1 + 5 gradually declined after LTX. Early after LTX,
      serum HLA-G levels were higher in patients with acute rejection episodes than
      nonrejectors. Late after LTX, serum HLA-G levels did not differ between
      operationally tolerant patients and patients on regular immunosuppressive
      therapy. CONCLUSIONS: Our data do not support a graft-protective role for HLA-G
      after LTX, but show that end-stage liver diseases are associated with HLA-G
      expression on hepatocytes, which may determine a negative feedback to protect the
      liver against immunological damage.

PMID- 25961489
TI  - Mechanisms of cancer cell killing by the adenovirus E4orf4 protein.
AB  - During adenovirus (Ad) replication the Ad E4orf4 protein regulates progression
      from the early to the late phase of infection. However, when E4orf4 is expressed
      alone outside the context of the virus it induces a non-canonical mode of
      programmed cell death, which feeds into known cell death pathways such as
      apoptosis or necrosis, depending on the cell line tested. E4orf4-induced cell
      death has many interesting and unique features including a higher susceptibility
      of cancer cells to E4orf4-induced cell killing compared with normal cells,
      caspase-independence, a high degree of evolutionary conservation of the signaling
      pathways, a link to perturbations of the cell cycle, and involvement of two
      distinct cell death programs, in the nucleus and in the cytoplasm. Several E4orf4
      interacting proteins including its major partners, protein phosphatase 2A (PP2A)
      and Src family kinases, contribute to induction of cell death. The various
      features of E4orf4-induced cell killing as well as studies to decipher the
      underlying mechanisms are described here. Many explanations for the cancer
      specificity of E4orf4-induced cell death have been proposed, but a full
      understanding of the reasons for the different susceptibility of cancer and
      normal cells to killing by E4orf4 will require a more detailed analysis of the
      complex E4orf4 signaling network. An improved understanding of the mechanisms
      involved in this unique mode of programmed cell death may aid in design of novel
      E4orf4-based cancer therapeutics. 

PMID- 25961488
TI  - Alphaviruses in gene therapy.
AB  - Alphavirus vectors present an attractive approach for gene therapy applications
      due to the rapid and simple recombinant virus particle production and their broad
      range of mammalian host cell transduction. Mainly three types of alphavirus
      vectors, namely naked RNA, recombinant particles and DNA/RNA layered vectors,
      have been subjected to preclinical studies with the goal of achieving
      prophylactic or therapeutic efficacy, particularly in oncology. In this context,
      immunization with alphavirus vectors has provided protection against challenges
      with tumor cells. Moreover, alphavirus intratumoral and systemic delivery has
      demonstrated substantial tumor regression and significant prolonged survival
      rates in various animal tumor models. Recent discoveries of the strong
      association of RNA interference and disease have accelerated gene therapy based
      approaches, where alphavirus-based gene delivery can play an important role. 

PMID- 25961491
TI  - The Effectiveness of Culture-Directed Preemptive Anti-Aspergillus Treatment in
      Lung Transplant Recipients at One Year After Transplant.
AB  - BACKGROUND: Invasive pulmonary aspergillosis (IPA) is a significant complication
      after lung transplantation. However, the risk factors for IPA in patients
      colonized with Aspergillus species, and the effectiveness of culture-directed
      preemptive treatment, are not well known. METHODS: We studied 328 lung transplant
      recipients, from January 2006 to July 2009, with 1-year follow-up. Risk factors
      and effectiveness of culture-directed preemptive treatment were evaluated via a
      Cox-proportional hazard model. RESULTS: Seventy-one recipients (21.6%) developed
      invasive fungal infections, including 29 patients (8.8%) with IPA. Only 48.3%
      (14/29) of patients with IPA had pretransplantation or posttransplantation airway
      colonization with Aspergillus spp. In the Cox-proportional hazard model,
      treatment with rabbit antithymocyte globulin was significantly associated with
      posttransplant IPA in patients with Aspergillus colonization (hazards ratio,
      4.25; 95% confidence interval, 1.09-16.6). Preemptive antifungal treatment for 3
      months was significantly associated with a lower rate of IPA (0% [0/36] vs 18%
      [14/77]; P = 0.003, odds ratio, 0.8; 95% confidence interval, 0.7-0.9) but did
      not impact mortality. CONCLUSIONS: Our data suggest that almost half the cases of
      IPA occurred in patients without pretransplantation or posttransplantation airway
      colonization with Aspergillus spp. Among patients with Aspergillus colonization,
      use of rabbit antithymocyte globulin was associated with 4-fold risk of
      subsequent development of IPA. Invasive pulmonary aspergillosis was an
      independent risk factor for 1-year mortality. Use of preemptive antifungal
      treatment for 3 months may be associated with significant reduction of IPA
      without influencing mortality.

PMID- 25961493
TI  - Lactoferrin-loaded contact lenses: eye protection against oxidative stress.
AB  - PURPOSE: Tear fluid contains antioxidative compounds, vitamin C, glutathione,
      superoxide dismutase, and lactoferrin (LF), which protect the corneal epithelium
      from the effects of ultraviolet irradiation, direct airflow, and chemical agents.
      However, these natural defenses against oxidative stress can decrease, favoring
      the development of anterior eye disorders, such as keratoconus, dry eye, and
      Sjogren syndrome. LF is an iron-binding glycoprotein, present in mammalian
      secretions such as tears and milk, endowed with different physiological functions
      such as antimicrobial, antiviral, and antioxidant activities. In this work, we
      studied the capability of different soft contact lenses to adsorb and release LF
      to restore cellular viability in oxidative stress conditions. METHODS: Three
      types of contact lenses (filcon V, galyfilcon A, and filcon IB) were loaded with
      LF and then incubated with TsA or human corneal epithelial primary cells. After
      oxidative stress induction with 250 MUM or 125 MUM H2O2, cell viability was
      evaluated. RESULTS: Data showed that the highest quantity of LF loaded in contact
      lenses was between 61 MUg (for filcon V) and 39 MUg (for filcon IB); the release
      was between 49% and 100% of protein adsorbed. LF released from contact lenses
      maintained its antioxidant activity at least for 24 hours and was able to protect
      human epithelial cells from the detrimental effects of oxidative stress.
      CONCLUSIONS: These results demonstrate that LF-loaded contact lenses could
      represent a new therapeutic approach to treat ocular surface pathologies
      characterized by high levels of oxidative stress.

PMID- 25961492
TI  - Comparison of galectin expression signatures in rejected and accepted murine
      corneal allografts.
AB  - PURPOSE: Although members of the galectin family of carbohydrate-binding proteins
      are thought to play a role in the immune response and regulation of allograft
      survival, little is known about the galectin expression signature in failed
      corneal grafts. The aim of this study was to compare the galectin expression
      pattern in accepted and rejected murine corneal allografts. METHODS: Using BALB/c
      mice as recipients and C57BL/6 mice as donors, a total of 57 transplants were
      successfully performed. One week after transplantation, the grafts were scored
      for opacity by slit-lamp microscopy. Opacity scores of 3+ or greater on
      postoperative week 4 were considered rejected. Grafted corneas were harvested on
      postoperative week 4, and their galectin expressions were analyzed by Western
      blot and immunofluorescence staining. RESULTS: As determined by the Western blot
      analyses, galectins-1, 3, 7, 8 and 9 were expressed in normal corneas. Although
      in both accepted and rejected grafts, expression levels of the 5 lectins were
      upregulated compared with normal corneas, there were distinct differences in the
      expression levels of galectins-8 and 9 between accepted and rejected grafts, as
      both the Western blot and immunofluorescence staining revealed that galectin-8 is
      upregulated, whereas galectin-9 is downregulated in the rejected grafts compared
      with the accepted grafts. CONCLUSIONS: Our findings that corneal allograft
      rejection is associated with increased galectin-8 expression and reduced galectin
      9 expression, support the hypothesis that galectin-8 may reduce graft survival,
      whereas galectin-9 may promote graft survival. As a potential therapeutic
      intervention, inhibition of galectin-8 and/or treatment with exogenous galectin-9
      may enhance corneal allograft survival rates.

PMID- 25961494
TI  - Traumatic keratoplasty rupture resulting from continuous positive airway pressure
      mask.
AB  - PURPOSE: To report a rare case of traumatic wound dehiscence caused by the use of
      a continuous positive airway pressure (CPAP) mask in a patient with chronic
      obstructive pulmonary disease (COPD) after penetrating keratoplasty (PKP).
      METHODS: Observational case report. CASE REPORT: A 55-year-old man who was
      treated with uncomplicated PKP due to pellucid marginal corneal degeneration in
      the right eye 9 months earlier presented to the emergency department after a
      globe rupture caused by dislocation of his CPAP mask during sleep. The best
      corrected visual acuity (BCVA) was light perception in the right eye. The corneal
      graft was dehisced from 12 over 3 to 6 o'clock (180 degrees) with interruption of
      the double running corneal sutures and nasal iris as well as vitreous
      incarceration. The graft was resutured in place with 33 interrupted 10-0
      monofilament nylon sutures. The BCVA improved to 20/100 three months after globe
      reconstruction. CONCLUSIONS: This case underlines the necessity of education for
      patients undergoing keratoplasty regarding the use of protective eyewear, to
      avoid predictable or accidental ocular injuries and graft dehiscence or its
      subsequent consequences. CPAP masks should be fitted (eyeball sparing) to the
      margins of the orbit after PKP.

PMID- 25961495
TI  - A Brief Screening Tool to Assess the Risk of Contracting HIV Infection Among
      Active Injection Drug Users.
AB  - OBJECTIVE: To incorporate preexposure prophylaxis and other biomedical or
      intensive behavioral interventions into the care of injection drug users (IDUs),
      health care providers need validated, rapid, risk screening tools for identifying
      persons at highest risk of incident HIV infection. METHODS: To develop and
      validate a brief screening tool for assessing the risk of contracting HIV (ARCH),
      we included behavioral and HIV test data from 1904 initially HIV-uninfected men
      and women enrolled and followed in the AIDS Linked to the Intravenous Experience
      prospective cohort study between 1988 and 2008. Using logistic regression
      analyses with generalized estimating equations, we identified significant
      predictors of incident HIV infection, then rescaled and summed their regression
      coefficients to create a risk score. RESULTS: The final logistic regression model
      included age, engagement in a methadone maintenance program, and a composite
      injection risk score obtained by counting the number of the following 5 behaviors
      reported during the past 6 months: injection of heroin, injection of cocaine,
      sharing a cooker, sharing needles, or visiting a shooting gallery. The area under
      the receiver operating characteristic curve was 0.720; possible scores on the
      index ranged from 0 to 100 and a score 46 or greater had a sensitivity of 86.2%
      and a specificity of 42.5%, appropriate for a screening tool. DISCUSSION: We
      developed an easy to administer 7-question screening tool with a cutoff that is
      predictive of incident HIV infection in a large prospective cohort of IDUs in
      Baltimore. The ARCH-IDUs screening tool can be used to prioritize persons who are
      injecting illicit drugs for consideration of preexposure prophylaxis and other
      intensive HIV prevention efforts.

PMID- 25961496
TI  - Prescription Medication Obtainment Methods and Misuse.
AB  - BACKGROUND: Abuse of prescription medications is an ever-expanding epidemic in
      the United States. OBJECTIVE: This study intends to help provide physicians with
      more knowledge about the behaviors that patients with a substance use disorder
      may exhibit in an effort to obtain medications. DESIGN: Patients who were willing
      to participate in the survey were interviewed by a physician. SETTING: Patients
      were screened, selected, and interviewed while participating in an inpatient
      rehabilitation program. RESULTS: Thirty-six patients completed the survey. There
      was a mean of 50.2 prescriptions per person. An average of 1.2 states was
      utilized by the surveyed patient population. There was an average of 2.11
      providers seen per patient. Data show that 78% of patients surveyed utilized more
      than one pharmacy. The type of medications obtained by respondents were as
      follows: opioids, 35 (97.2%); sedative-hypnotics, 17 (47.4%); and amphetamines, 2
      (5.5%). Seventy-five percent of patients (27 of the 36) stated that they feigned
      symptoms in attempts to obtain prescriptions. Two patients used a falsified (via
      mislabeling) magnetic resonance image of injury. Two patients paid a physician
      outright for the prescription. Three patients (8.3%) stated they would physically
      harm themselves in an attempt to obtain prescription medications. CONCLUSIONS: It
      may be noted that patients seeking prescription medications tend to utilize more
      than one physician and more than one pharmacy. On the basis of survey results, it
      seems that primary care and pain management physicians are considered the easiest
      venues to obtain prescription medications. It suggests that patients will go to
      great lengths to obtain prescription medications.

PMID- 25961498
TI  - Poly(L-lysine) Interfaces via Dual Click Reactions on Surface-Bound Custom
      Designed Dithiol Adsorbates.
AB  - Surfaces modified with poly(L-lysine) can be used to immobilize selected
      biomolecules electrostatically. This report describes the preparation of a set of
      self-assembled monolayers (SAMs) from three different azide-terminated adsorbates
      as platforms for performing controlled surface attachments and as a means of
      determining the parameters that afford stable poly(L-lysine)-modified SAM
      surfaces having controlled packing densities. A maleimide-terminated alkyne
      linker was "clicked" to the azide-terminated surfaces via a copper-catalyzed
      cycloaddition reaction to produce the attachment sites for the polypeptides. A
      thiol-Michael addition was then used to immobilize cysteine-terminated poly(L
      lysine) moieties on the gold surface, avoiding adsorbate self-reactions with this
      two-step procedure. Each step in this process was analyzed by ellipsometry, X-ray
      photoelectron spectroscopy, polarization modulation infrared reflection
      absorption spectroscopy, and contact angle goniometry to determine which
      adsorbate structure most effectively produced the targeted polypeptide interface.
      Additionally, a series of mixed SAMs using an azidoalkanethiol in combination
      with a normal alkanethiol having an equivalent alkyl chain were prepared to
      provide data to determine how dilution of the azide reactive site on the SAM
      surface influences the initial click reaction. Overall, the collected data
      demonstrate the advantages of an appropriately designed bidentate absorbate and
      its potential to form effective platforms for biomolecule surface attachment via
      click reactions.

PMID- 25961497
TI  - Simultaneously Targeting the NS3 Protease and Helicase Activities for More
      Effective Hepatitis C Virus Therapy.
AB  - This study examines the specificity and mechanism of action of a recently
      reported hepatitis C virus (HCV) nonstructural protein 3 (NS3) helicase-protease
      inhibitor (HPI), and the interaction of HPI with the NS3 protease inhibitors
      telaprevir, boceprevir, danoprevir, and grazoprevir. HPI most effectively reduced
      cellular levels of subgenomic genotype 4a replicons, followed by genotypes 3a and
      1b replicons. HPI had no effect on HCV genotype 2a or dengue virus replicon
      levels. Resistance evolved more slowly to HPI than telaprevir, and HPI inhibited
      telaprevir-resistant replicons. Molecular modeling and analysis of the ability of
      HPI to inhibit peptide hydrolysis catalyzed by a variety of wildtype and mutant
      NS3 proteins suggested that HPI forms a bridge between the NS3 RNA-binding cleft
      and an allosteric site previously shown to bind other protease inhibitors. In
      most combinations, the antiviral effect of HPI was additive with telaprevir and
      boceprevir, minor synergy was observed with danoprevir, and modest synergy was
      observed with grazoprevir. 

PMID- 25961499
TI  - Photoluminescent Evolution Induced by Structural Transformation Through Thermal
      Treating in the Red Narrow-Band Phosphor K2GeF6:Mn4+.
AB  - This study explored optimal preparation conditions for K2GeF6:Mn(4+) red
      phosphors by using chemical coprecipitation method. The prepared hexagonal P3m1
      K2GeF6:Mn(4+) exhibited efficient red emission, high color purity, good Mn(4+)
      concentration stability, and low thermal quenching. Structural evolution from
      hexagonal P3m1 to P63mc and then P63mc to cubic Fm3m occurred after thermal
      treatment at approximately 400 and 500  degrees C, respectively. Hexagonal P63mc
      phase showed an obvious zero phonon line peak at 621 nm, whereas cubic Fm3m phase
      showed no red emission. Yellowish K2GeF6:Mn(4+) with both hexagonal P3m1 and
      P63mc symmetries are promising commercial red phosphors for white light-emitting
      diodes. 

PMID- 25961500
TI  - Interferon gamma-induced protein 10 is associated with insulin resistance and
      incident diabetes in patients with nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is an important risk factor for the
      development of type 2 diabetes mellitus. Interferon gamma-induced protein 10 (IP
      10), a proinflammatory chemokine, plays a crucial role in inflammatory diseases.
      This cross-sectional pilot study investigated whether circulating IP-10 is
      associated with the progression of liver disease, and prediabetes in patients
      with NAFLD. A total of 90 patients with NAFLD alone (n = 48) or NAFLD with
      incident diabetes (n = 42) and 43 controls participated in this study. Fasting
      plasma was used to assess metabolic parameters, inflammatory factors, endotoxin
      levels, and malondialdehyde (MDA) concentrations. Insulin resistance was
      estimated using homeostatic model assessment (HOMA-IR). IP-10 levels were
      significantly higher in patients with NAFLD alone (median (interquartile range):
      369.44 (309.30-418.97) pg/mL) and in those with incident diabetes (418.99 (330.73
      526.04) pg/mL) than in controls (293.37 (214.10-331.57) pg/mL) (P < 0.001). IP-10
      levels were positively correlated with levels of alanine aminotransferase, hs
      CRP, MDA, MCP-1, and TNF-alpha as well as HOMA-IR values. Ordinal logistic
      regression analysis revealed IP-10 was an independent risk factor associated with
      progressive liver injury, insulin resistance and incident diabetes. Circulating
      IP-10 may be a non-invasive biomarker for disease progression and subsequent
      diabetes development of NAFLD. 

PMID- 25961501
TI  - The Association between Serum Uric Acid Levels and the Prevalence of Vulnerable
      Atherosclerotic Carotid Plaque: A Cross-sectional Study.
AB  - Little is known about the associations between serum uric acid (SUA) levels and
      atherosclerotic carotid plaque vulnerability. The aim of this study was to assess
      the associations of SUA levels with the prevalence of vulnerable atherosclerotic
      carotid plaque in a community-based cohort. In the Asymptomatic Polyvascular
      Abnormalities Community (APAC) study, cross-sectional data from 2860 Chinese
      residents who underwent SUA measurement and ultrasonographic assessment of
      carotid plaque were analyzed. Multivariable logistic regression models were used
      to assess the associations of SUA levels with presence of vulnerable carotid
      plaque. After adjustment for potential confounders, SUA levels were significantly
      associated with the prevalence of vulnerable plaque amongst the middle-aged
      adults (odds ratio [OR] = 1.19, 95% confidence interval [CI]: 1.11-1.28).
      Compared to the lowest quartile, quartiles 2, 3 and 4 had a prevalence OR of 1.33
      (1.02-1.74), 1.70 (1.27-2.27) and 2.05 (1.53-2.75), respectively, for the
      presence of vulnerable carotid plaque (p for trend across quartiles < 0.001). In
      the APAC study, elevated SUA levels were independently associated with the
      prevalence of vulnerable carotid plaque in middle-aged adults. 

PMID- 25961502
TI  - Degradation of lipid droplet-associated proteins by chaperone-mediated autophagy
      facilitates lipolysis.
AB  - Chaperone-mediated autophagy (CMA) selectively degrades a subset of cytosolic
      proteins in lysosomes. A potent physiological activator of CMA is nutrient
      deprivation, a condition in which intracellular triglyceride stores or lipid
      droplets (LDs) also undergo hydrolysis (lipolysis) to generate free fatty acids
      for energetic purposes. Here we report that the LD-associated proteins perilipin
      2 (PLIN2) and perilipin 3 (PLIN3) are CMA substrates and their degradation
      through CMA precedes lipolysis. In vivo studies revealed that CMA degradation of
      PLIN2 and PLIN3 was enhanced during starvation, concurrent with elevated levels
      of cytosolic adipose triglyceride lipase (ATGL) and macroautophagy proteins on
      LDs. CMA blockage both in cultured cells and mouse liver or expression of CMA
      resistant PLINs leads to reduced association of ATGL and macrolipophagy-related
      proteins with LDs and the subsequent decrease in lipid oxidation and accumulation
      of LDs. We propose a role for CMA in LD biology and in the maintenance of lipid
      homeostasis. 

PMID- 25961503
TI  - Condensin confers the longitudinal rigidity of chromosomes.
AB  - In addition to inter-chromatid cohesion, mitotic and meiotic chromatids must have
      three physical properties: compaction into 'threads' roughly co-linear with their
      DNA sequence, intra-chromatid cohesion determining their rigidity, and a
      mechanism to promote sister chromatid disentanglement. A fundamental issue in
      chromosome biology is whether a single molecular process accounts for all three
      features. There is universal agreement that a pair of Smc-kleisin complexes
      called condensin I and II facilitate sister chromatid disentanglement, but
      whether they also confer thread formation or longitudinal rigidity is either
      controversial or has never been directly addressed respectively. We show here
      that condensin II (beta-kleisin) has an essential role in all three processes
      during meiosis I in mouse oocytes and that its function overlaps with that of
      condensin I (gamma-kleisin), which is otherwise redundant. Pre-assembled meiotic
      bivalents unravel when condensin is inactivated by TEV cleavage, proving that it
      actually holds chromatin fibres together. 

PMID- 25961506
TI  - Lewis acid activation of carbodicarbene catalysts for Rh-catalyzed hydroarylation
      of dienes.
AB  - The activation of carbodicarbene (CDC)-Rh(I) pincer complexes by secondary
      binding of metal salts is reported for the catalytic site-selective hydro
      heteroarylation of dienes (up to 98% yield and >98:2 gamma:alpha). Reactions are
      promoted by 5 mol % of a readily available tridentate (CDC)-Rh complex in the
      presence of an inexpensive lithium salt. The reaction is compatible with a
      variety of terminal and internal dienes and tolerant of ester, alkyl halide, and
      boronate ester functional groups. X-ray data and mechanistic experiments provide
      support for the role of the metal salts on catalyst activation and shed light on
      the reaction mechanism. The increased efficiency (120 to 22  degrees C) made
      available by catalytic amounts of metal salts to catalysts containing C(0) donors
      is a significant aspect of the disclosed studies. 

PMID- 25961504
TI  - Inactivation of a Galpha(s)-PKA tumour suppressor pathway in skin stem cells
      initiates basal-cell carcinogenesis.
AB  - Genomic alterations in GNAS, the gene coding for the Galphas heterotrimeric G
      protein, are associated with a large number of human diseases. Here, we explored
      the role of Galphas on stem cell fate decisions by using the mouse epidermis as a
      model system. Conditional epidermal deletion of Gnas or repression of PKA
      signalling caused a remarkable expansion of the stem cell compartment, resulting
      in rapid basal-cell carcinoma formation. In contrast, inducible expression of
      active Galphas in the epidermis caused hair follicle stem cell exhaustion and
      hair loss. Mechanistically, we found that Galphas-PKA disruption promotes the
      cell autonomous Sonic Hedgehog pathway stimulation and Hippo signalling
      inhibition, resulting in the non-canonical activation of GLI and YAP1. Our study
      highlights an important tumour suppressive function of Galphas-PKA, limiting the
      proliferation of epithelial stem cells and maintaining proper hair follicle
      homeostasis. These findings could have broad implications in multiple
      pathophysiological conditions, including cancer. 

PMID- 25961505
TI  - A nuclear role for the respiratory enzyme CLK-1 in regulating mitochondrial
      stress responses and longevity.
AB  - The coordinated regulation of mitochondrial and nuclear activities is essential
      for cellular respiration and its disruption leads to mitochondrial dysfunction, a
      hallmark of ageing. Mitochondria communicate with nuclei through retrograde
      signalling pathways that modulate nuclear gene expression to maintain
      mitochondrial homeostasis. The monooxygenase CLK-1 (human homologue COQ7) was
      previously reported to be mitochondrial, with a role in respiration and
      longevity. We have uncovered a distinct nuclear form of CLK-1 that independently
      regulates lifespan. Nuclear CLK-1 mediates a retrograde signalling pathway that
      is conserved from Caenorhabditis elegans to humans and is responsive to
      mitochondrial reactive oxygen species, thus acting as a barometer of oxidative
      metabolism. We show that, through modulation of gene expression, the pathway
      regulates both mitochondrial reactive oxygen species metabolism and the
      mitochondrial unfolded protein response. Our results demonstrate that a
      respiratory enzyme acts in the nucleus to control mitochondrial stress responses
      and longevity. 

PMID- 25961507
TI  - Reactive Oxygen Species Production Mediated by Humic-like Substances in
      Atmospheric Aerosols: Enhancement Effects by Pyridine, Imidazole, and Their
      Derivatives.
AB  - Ambient particulate matter (PM) can cause adverse health effects via their
      ability to produce reactive oxygen species (ROS). Humic-like substances (HULIS),
      a complex mixture of amphiphilic organic compounds, have been demonstrated to
      contain the majority of redox activity in the water-extractable organic fraction
      of PM. Reduced organic nitrogen compounds, such as alkaloids resulting from
      biomass burning emissions, are among HULIS constituents. In this study, we
      examined the redox activities of pyridine, imidazole and their alkyl derivatives
      using a cell-free dithiothreitol (DTT) assay under simulated physiological
      conditions (37  degrees C, pH = 7.40). These compounds were found to have little
      redox activity on their own as measured by the DTT assay, but they enhanced ROS
      generation catalyzed by 1,4-naphthoquinone (as a model quinone compound) and
      HULIS isolated from multiple aerosol samples. The enhancement effect by the
      individual nitrogen-containing bases was determined to be proportional to their
      amount in the assay solutions. It is postulated that the underlying mechanism
      involves the unprotonated N atom acting as a H-bonding acceptor to facilitate
      hydrogen-atom transfer in the ROS generation cycle. The enhancement capability
      was found to increase with their basicity (i.e., pKa of their conjugated acids,
      BH(+)), consistent with the proposed mechanism for enhancement. Among the
      imidazole homologues, a linear relationship was observed between the enhancement
      factors (in log scale) of the unprotonated form of the imidazole compounds (B)
      and the pKa of their conjugated acids (BH(+)). This relationship predicts that
      the range of alkylimidazole homologues (C6-C13) observed in atmospheric HULIS
      would be 1.5-4.4 times more effective than imidazole in facilitating HULIS
      mediated ROS generation. Our work reveals that the ability of atmospheric PM
      organics to catalyze generation of ROS in cells could be affected by coexisting
      redox inactive organic constituents and suggests further work deploying multiple
      assays be conducted to quantify redox capabilities and enhancement effects of the
      HULIS components. 

PMID- 25961508
TI  - High-efficiency resonant amplification of weak magnetic fields for single spin
      magnetometry at room temperature.
AB  - Magnetic resonance techniques not only provide powerful imaging tools that have
      revolutionized medicine, but they have a wide spectrum of applications in other
      fields of science such as biology, chemistry, neuroscience and physics. However,
      current state-of-the-art magnetometers are unable to detect a single nuclear spin
      unless the tip-to-sample separation is made sufficiently small. Here, we
      demonstrate theoretically that by placing a ferromagnetic particle between a
      nitrogen-vacancy magnetometer and a target spin, the magnetometer sensitivity is
      improved dramatically. Using materials and techniques that are already
      experimentally available, our proposed set-up is sensitive enough to detect a
      single nuclear spin within ten milliseconds of data acquisition at room
      temperature. The sensitivity is practically unchanged when the ferromagnet
      surface to the target spin separation is smaller than the ferromagnet lateral
      dimensions; typically about a tenth of a micrometre. This scheme further benefits
      when used for nitrogen-vacancy ensemble measurements, enhancing sensitivity by an
      additional three orders of magnitude. 

PMID- 25961510
TI  - Edge-mode superconductivity in a two-dimensional topological insulator.
AB  - Topological superconductivity is an exotic state of matter that supports Majorana
      zero-modes, which have been predicted to occur in the surface states of three
      dimensional systems, in the edge states of two-dimensional systems, and in one
      dimensional wires. Localized Majorana zero-modes obey non-Abelian exchange
      statistics, making them interesting building blocks for topological quantum
      computing. Here, we report superconductivity induced in the edge modes of
      semiconducting InAs/GaSb quantum wells, a two-dimensional topological insulator.
      Using superconducting quantum interference we demonstrate gate-tuning between
      edge-dominated and bulk-dominated regimes of superconducting transport. The edge
      dominated regime arises only under conditions of high-bulk resistivity, which we
      associate with the two-dimensional topological phase. These experiments establish
      InAs/GaSb as a promising platform for the confinement of Majoranas into localized
      states, enabling future investigations of non-Abelian statistics. 

PMID- 25961509
TI  - Self-replication of DNA rings.
AB  - Biology provides numerous examples of self-replicating machines, but artificially
      engineering such complex systems remains a formidable challenge. In particular,
      although simple artificial self-replicating systems including wooden blocks,
      magnetic systems, modular robots and synthetic molecular systems have been
      devised, such kinematic self-replicators are rare compared with examples of
      theoretical cellular self-replication. One of the principal reasons for this is
      the amount of complexity that arises when you try to incorporate self-replication
      into a physical medium. In this regard, DNA is a prime candidate material for
      constructing self-replicating systems due to its ability to self-assemble through
      molecular recognition. Here, we show that DNA T-motifs, which self-assemble into
      ring structures, can be designed to self-replicate through toehold-mediated
      strand displacement reactions. The inherent design of these rings allows the
      population dynamics of the systems to be controlled. We also analyse the
      replication scheme within a universal framework of self-replication and derive a
      quantitative metric of the self-replicability of the rings. 

PMID- 25961511
TI  - Magnetoluminescence and valley polarized state of a two-dimensional electron gas
      in WS2 monolayers.
AB  - Materials often exhibit fundamentally new phenomena in reduced dimensions that
      potentially lead to novel applications. This is true for single-layer, two
      dimensional semiconductor crystals of transition-metal dichalcogenides, MX2 (M =
      Mo, W and X = S, Se). They exhibit direct bandgaps with energies in the visible
      region at the two non-equivalent valleys in the Brillouin zone. This makes them
      suitable for optoelectronic applications that range from light-emitting diodes to
      light harvesting and light sensors, and to valleytronics. Here, we report the
      results of a magnetoluminescence study of WS2 single-layer crystals in which the
      strong spin-orbit interaction additionally locks the valley and spin degrees of
      freedom. The recombination of the negatively charged exciton in the presence of a
      two-dimensional electron gas (2DEG) is found to be circularly polarized at zero
      magnetic field despite being excited with unpolarized light, which indicates that
      the existence of a valley polarized 2DEG is caused by valley and spin locking and
      strong electron-electron interactions. 

PMID- 25961512
TI  - Dienals derived from pyridinium salts and their subsequent application in natural
      product synthesis.
AB  - Transformation of quaternary pyridinium compounds into functionalized conjugated
      dienes can be adapted to natural product synthesis with great effect. Most
      conspicuously, the transformation has been employed in the preparation of
      polyenic structures. However, in a more convoluted application, polycyclic
      systems have arisen from elaboration of the diene motif. The goal of the present
      account is to survey the utility of dienals derived from pyridinium salts as the
      means to establish molecular architecture featured in natural products. 

PMID- 25961513
TI  - Four-state ferroelectric spin-valve.
AB  - Spin-valves had empowered the giant magnetoresistance (GMR) devices to have
      memory. The insertion of thin antiferromagnetic (AFM) films allowed two stable
      magnetic field-induced switchable resistance states persisting in remanence. In
      this letter, we show that, without the deliberate introduction of such an AFM
      layer, this functionality is transferred to multiferroic tunnel junctions (MFTJ)
      allowing us to create a four-state resistive memory device. We observed that the
      ferroelectric/ferromagnetic interface plays a crucial role in the stabilization
      of the exchange bias, which ultimately leads to four robust electro tunnel
      electro resistance (TER) and tunnel magneto resistance (TMR) states in the
      junction. 

PMID- 25961515
TI  - Synthesis and Transfer of Large-Area Monolayer WS2 Crystals: Moving Toward the
      Recyclable Use of Sapphire Substrates.
AB  - Two-dimensional layered transition metal dichalcogenides (TMDs) show intriguing
      potential for optoelectronic devices due to their exotic electronic and optical
      properties. Only a few efforts have been dedicated to large-area growth of TMDs.
      Practical applications will require improving the efficiency and reducing the
      cost of production, through (1) new growth methods to produce large size TMD
      monolayer with less-stringent conditions, and (2) nondestructive transfer
      techniques that enable multiple reuse of growth substrate. In this work, we
      report to employ atmospheric pressure chemical vapor deposition (APCVD) for the
      synthesis of large size (>100 MUm) single crystals of atomically thin tungsten
      disulfide (WS2), a member of TMD family, on sapphire substrate. More importantly,
      we demonstrate a polystyrene (PS) mediated delamination process via capillary
      force in water which reduces the etching time in base solution and imposes only
      minor damage to the sapphire substrate. The transferred WS2 flakes are of
      excellent continuity and exhibit comparable electron mobility after several
      growth cycles on the reused sapphire substrate. Interestingly, the
      photoluminescence emission from WS2 grown on the recycled sapphire is much higher
      than that on fresh sapphire, possibly due to p-type doping of monolayer WS2
      flakes by a thin layer of water intercalated at the atomic steps of the recycled
      sapphire substrate. The growth and transfer techniques described here are
      expected to be applicable to other atomically thin TMD materials. 

PMID- 25961514
TI  - Molecular probes for fluorescence lifetime imaging.
AB  - Visualization of biological processes and pathologic conditions at the cellular
      and tissue levels largely relies on the use of fluorescence intensity signals
      from fluorophores or their bioconjugates. To overcome the concentration
      dependency of intensity measurements, evaluate subtle molecular interactions, and
      determine biochemical status of intracellular or extracellular microenvironments,
      fluorescence lifetime (FLT) imaging has emerged as a reliable imaging method
      complementary to intensity measurements. Driven by a wide variety of dyes
      exhibiting stable or environment-responsive FLTs, information multiplexing can be
      readily accomplished without the need for ratiometric spectral imaging. With
      knowledge of the fluorescent states of the molecules, it is entirely possible to
      predict the functional status of biomolecules or microevironment of cells.
      Whereas the use of FLT spectroscopy and microscopy in biological studies is now
      well-established, in vivo imaging of biological processes based on FLT imaging
      techniques is still evolving. This review summarizes recent advances in the
      application of the FLT of molecular probes for imaging cells and small animal
      models of human diseases. It also highlights some challenges that continue to
      limit the full realization of the potential of using FLT molecular probes to
      address diverse biological problems and outlines areas of potential high impact
      in the future. 

PMID- 25961516
TI  - Preschool-age problem behavior and teacher-child conflict in school: direct and
      moderation effects by preschool organization.
AB  - The hypothesis was tested that the new open-group Norwegian day-care centers
      would more than traditionally organized centers negatively affect (a) current and
      (b) future teacher-child relationships, and (c) the developmental legacy of
      preschool problem behavior. The focus was on eight hundred and fifty 4-year-olds
      from 153 centers who were followed up in first grade. Results of this natural
      quasi-experiment revealed that children from open-group centers (a) experienced
      less teacher-child closeness in preschool and (b) more teacher-child conflict in
      first grade, and (c) that high levels of preschool problem behavior forecast
      especially high levels of future teacher-child conflict, but only for children
      from open-group centers. Results highlight the importance of spatial and social
      organization of day care and their translational implications. 

PMID- 25961517
TI  - Multi-Target QSAR Approaches for Modeling Protein Inhibitors. Simultaneous
      Prediction of Activities Against Biomacromolecules Present in Gram-Negative
      Bacteria.
AB  - Drug discovery is aimed at finding therapeutic agents for the treatment of many
      diverse diseases and infections. However, this is a very slow an expensive
      process, and for this reason, in silico approaches are needed to rationalize the
      search for new molecular entities with desired biological profiles. Models
      focused on quantitative structure-activity relationships (QSAR) have constituted
      useful complementary tools in medicinal chemistry, allowing the virtual
      predictions of dissimilar pharmacological activities of compounds. In the last 10
      years, multi-target (mt) QSAR models have been reported, representing great
      advances with respect to those models generated from classical approaches. Thus,
      mt- QSAR models can simultaneously predict activities against different
      biological targets (proteins, microorganisms, cell lines, etc.) by using large
      and heterogeneous datasets of chemicals. The present review is devoted to discuss
      the most promising mt-QSAR models, particularly those developed for the
      prediction of protein inhibitors. We also report the first multi-tasking QSAR
      (mtk-QSAR) model for simultaneous prediction of inhibitors against
      biomacromolecules (specifically proteins) present in Gram-negative bacteria. This
      model allowed us to consider both different proteins and multiple experimental
      conditions under which the inhibitory activities of the chemicals were
      determined. The mtk-QSAR model exhibited accuracies higher than 98% in both
      training and prediction sets, also displaying a very good performance in the
      classification of active and inactive cases that depended on the specific
      elements of the experimental conditions. The physicochemical interpretations of
      the molecular descriptors were also analyzed, providing important insights
      regarding the molecular patterns associated with the appearance/enhancement of
      the inhibitory potency. 

PMID- 25961518
TI  - Nano-QSPR Modelling of Carbon-Based Nanomaterials Properties.
AB  - Evaluation of chemical and physical properties of nanomaterials is of critical
      importance in a broad variety of nanotechnology researches. There is an
      increasing interest in computational methods capable of predicting properties of
      new and modified nanomaterials in the absence of time-consuming and costly
      experimental studies. Quantitative Structure- Property Relationship (QSPR)
      approaches are progressive tools in modelling and prediction of many
      physicochemical properties of nanomaterials, which are also known as nano-QSPR.
      This review provides insight into the concepts, challenges and applications of
      QSPR modelling of carbon-based nanomaterials. First, we try to provide a general
      overview of QSPR implications, by focusing on the difficulties and limitations on
      each step of the QSPR modelling of nanomaterials. Then follows with the most
      significant achievements of QSPR methods in modelling of carbon-based
      nanomaterials properties and their recent applications to generate predictive
      models. This review specifically addresses the QSPR modelling of physicochemical
      properties of carbon-based nanomaterials including fullerenes, single-walled
      carbon nanotube (SWNT), multi-walled carbon nanotube (MWNT) and graphene. 

PMID- 25961519
TI  - Metal Oxide Nanomaterials in Nanomedicine: Applications in Photodynamic Therapy
      and Potential Toxicity.
AB  - Metal oxide nanomaterials have exhibited excellent performance as nanomedicines
      in photodynamic therapy (PDT) for cancer and infection treatment. Their unique
      and tunable physicochemical properties advance them as promising alternatives in
      drug delivery, early diagnosis, imaging, and treatment against various tumors and
      infectious diseases. Moreover, the implementation of nanophototherapy in deep
      tissue sites is enhanced by advancements in photosensitization technology.
      Notwithstanding the progress made in emerging metal oxide nanomaterials-derived
      PDT, the potential toxicity towards adjunct tissues associated with this approach
      remains challenging. Regulation and legislation have also been recommended and
      subsequently enacted in response to public concerns related to large-scale
      production, transportation, use, and disposal of those nanomaterials.
      Consequently, a quantitative structure-activity relationship (QSAR) paradigm has
      been adopted and is widely used in evaluating and predicting the side effects of
      nanomedicines, thus influencing their design and fabrication. This article
      briefly reviews the application of metal oxide nanomaterials in PDT and their
      associated adverse impacts as reported in recent publications. The future trends
      and implications of this platform in nanomedicine are also highlighted. However,
      more studies and efforts have to be carried out for developing novel nano
      therapeutics with high selectivity, sensitivity, biocompatibility, and minimal
      side effects in PDT. 

PMID- 25961520
TI  - Computational Study of Nanosized Drug Delivery from Cyclodextrins, Crown Ethers
      and Hyaluronan in Pharmaceutical Formulations.
AB  - The problem in this work is the computational characterization of cyclodextrins,
      crown ethers and hyaluronan (HA) as hosts of inclusion complexes for nanosized
      drug delivery vehicles in pharmaceutical formulations. The difficulty is
      addressed through a computational study of some thermodynamic, geometric and
      topological properties of the hosts. The calculated properties of
      oligosaccharides of D-glucopyranoses allow these to act as co-solvents of
      polyanions in water. In crown ethers, the central channel is computed.
      Mucoadhesive polymer HA in formulations releases drugs in mucosas. Geometric,
      topological and fractal analyses are carried out with code TOPO. Reference
      calculations are performed with code GEPOL. From HA to HA.3Ca and hydrate, the
      hydrophilic solvent-accessible surface varies with the count of H-bonds. The
      fractal dimension rises. The dimension of external atoms rises resulting 1.725
      for HA. It rises going to HA.3Ca and hydrate. Nonburied minus molecular dimension
      rises and decays. Hydrate globularity is lower than O(water), Ca(2+) and O(HA).
      Ca(2+) rugosity is smaller than for hydrate, O(HA) and O(water). Ca(2+) and
      O(water) accessibilities are greater than hydrate. Conclusions are drawn on: (1)
      the relative stability of linear/cyclic and shorter/larger polymers; (2) the
      atomic analysis of properties allows determining the atoms with maximum
      reactivity. 

PMID- 25961521
TI  - Toxicity of 11 Metal Oxide Nanoparticles to Three Mammalian Cell Types In Vitro.
AB  - The knowledge on potential harmful effects of metallic nanomaterials lags behind
      their increased use in consumer products and therefore, the safety data on
      various nanomaterials applicable for risk assessment are urgently needed. In this
      study, 11 metal oxide nanoparticles (MeOx NPs) prepared using flame pyrolysis
      method were analyzed for their toxicity against human alveolar epithelial cells
      A549, human epithelial colorectal cells Caco2 and murine fibroblast cell line
      Balb/c 3T3. The cell lines were exposed for 24 h to suspensions of 3-100 MUg/mL
      MeOx NPs and cellular viability was evaluated using. Neutral Red Uptake (NRU)
      assay. In parallel to NPs, toxicity of soluble salts of respective metals was
      analyzed, to reveal the possible cellular effects of metal ions shedding from the
      NPs. The potency of MeOx to produce reactive oxygen species was evaluated in the
      cell-free assay. The used three cell lines showed comparable toxicity responses
      to NPs and their metal ion counterparts in the current test setting. Six MeOx NPs
      (Al2O3, Fe3O4, MgO, SiO2, TiO2, WO3) did not show toxic effects below 100 ug/mL.
      For five MeOx NPs, the averaged 24 h IC50 values for the three mammalian cell
      lines were 16.4 ug/mL for CuO, 22.4 ug/mL for ZnO, 57.3 ug/mL for Sb2O3, 132.3
      ug/mL for Mn3O4 and 129 ug/mL for Co3O4. Comparison of the dissolution level of
      MeOx and the toxicity of soluble salts allowed to conclude that the toxicity of
      CuO, ZnO and Sb2O3 NPs was driven by release of metal ions. The toxic effects of
      Mn3O4 and Co3O4 could be attributed to the ROS-inducing ability of these NPs. All
      the NPs were internalized by the cells according to light microscopy studies but
      also proven by TEM, and internalization of Co3O4 NPs seemed to be most prominent
      in this aspect. In conclusion, this work provides valuable toxicological data for
      a library of 11 MeOx NPs. Combining the knowledge on toxic or non-toxic nature of
      nanomaterials may be used for safe-by-design approach. 

PMID- 25961522
TI  - Reliable but Timesaving: In Search of an Efficient Quantum-chemical Method for
      the Description of Functional Fullerenes.
AB  - Fullerene and its derivatives are currently one of the most intensively
      investigated species in the area of nanomedicine and nanochemistry. Various
      unique properties of fullerenes are responsible for their wide range applications
      in industry, biology and medicine. A large pool of functionalized C60 and C70
      fullerenes is investigated theoretically at different levels of quantum
      mechanical theory. The semiempirial PM6 method, density functional theory with
      the B3LYP functional, and correlated ab initio MP2 method are employed to compute
      the optimized structures, and an array of properties for the considered species.
      In addition to the calculations for isolated molecules, the results of solution
      calculations are also reported at the DFT level, using the polarizable continuum
      model (PCM). Ionization potentials (IPs) and electron affinities (EAs) are
      computed by means of Koopmans' theorem as well as with the more accurate but
      computationally expensive DeltaSCF method. Both procedures yield comparable
      values, while comparison of IPs and EAs computed with different quantum
      mechanical methods shows surprisingly large differences. Harmonic vibrational
      frequencies are computed at the PM6 and B3LYP levels of theory and compared with
      each other. A possible application of the frequencies as 3D descriptors in the
      EVA (EigenVAlues) method is shown. All the computed data are made available, and
      may be used to replace experimental data in routine applications where large
      amounts of data are required, e.g. in structure-activity relationship studies of
      the toxicity of fullerene derivatives. 

PMID- 25961523
TI  - Computer-Aided Drug Design of Bioactive Natural Products.
AB  - Natural products have been an integral part of sustaining civilizations because
      of their medicinal properties. Past discoveries of bioactive natural products
      have relied on serendipity, and these compounds serve as inspiration for the
      generation of analogs with desired physicochemical properties. Bioactive natural
      products with therapeutic potential are abundantly available in nature and some
      of them are beyond exploration by conventional methods. The effectiveness of
      computational approaches as versatile tools for facilitating drug discovery and
      development has been recognized for decades, without exception, in the case of
      natural products. In the post-genomic era, scientists are bombarded with data
      produced by advanced technologies. Thus, rendering these data into knowledge that
      is interpretable and meaningful becomes an essential issue. In this regard,
      computational approaches utilize the existing data to generate knowledge that
      provides valuable understanding for addressing current problems and guiding the
      further research and development of new natural-derived drugs. Furthermore,
      several medicinal plants have been continuously used in many traditional medicine
      systems since antiquity throughout the world, and their mechanisms have not yet
      been elucidated. Therefore, the utilization of computational approaches and
      advanced synthetic techniques would yield great benefit to improving the world's
      health population and well-being. 

PMID- 25961524
TI  - On the Origins of Hepatitis C Virus NS5B Polymerase Inhibitory Activity Using
      Machine Learning Approaches.
AB  - Inhibition of non-structural protein 5B (NS5B) represents an attractive strategy
      for the therapeutic treatment of hepatitis C virus (HCV). In this study, machine
      learning classifiers such as artificial neural network (ANN), support vector
      machine (SVM), random forest (RF) and decision tree (DT) analyses were used to
      classify 970 compounds based on their physicochemical properties, including
      quantum chemical descriptors, constitutional descriptors, functional groups and
      molecular properties. Good predictive performance was obtained from all
      classifiers, providing accuracies ranging from 82.47-89.61% for external
      validation set. SVM was noted as the best classifier, indicated by its highest
      accuracy of 89.61%. The analyses were performed on data sets stratified by
      structural scaffolds (nucleoside and non-nucleoside) and bioactivities (active
      and inactive properties). In addition, a molecular fragment analysis was
      performed to investigate molecular substructures corresponding to biological
      activities. Furthermore, common substructures and potential functional groups
      governing the activities of active and inactive inhibitors were noted for the
      benefit of rational design and high-throughput screening towards potential HCV
      NS5B inhibitors. 

PMID- 25961525
TI  - Application of SMILES Notation Based Optimal Descriptors in Drug Discovery and
      Design.
AB  - SMILES notation based optimal descriptors as a universal tool for the QSAR
      analysis with further application in drug discovery and design is presented. The
      basis of this QSAR modeling is Monte Carlo method which has important advantages
      over other methods, like the possibility of analysis of a QSAR as a random event,
      is discussed. The advantages of SMILES notation based optimal descriptors in
      comparison to commonly used descriptors are defined. The published results of
      QSAR modeling with SMILES notation based optimal descriptors applied for various
      pharmacologically important endpoints are listed. The presented QSAR modeling
      approach obeys OECD principles and has mechanistic interpretation with
      possibility to identify molecular fragments that contribute in positive and
      negative way to studied biological activity, what is of big importance in
      computer aided drug design of new compounds with desired activity. 

PMID- 25961526
TI  - Ab Initio Studies of Anatase TiO2 (101) Surface-supported Au8 Clusters.
AB  - Supported transition metals on TiO2 surfaces have shown exceptional catalytic
      properties in many important process such as CO oxidation, selective propane
      oxidation, hydrogenation, water adsorption and other catalytic and photocatalytic
      oxidation reaction at low-temperature. Among the three polymorphs of TiO2, the
      anatase crystal is the more photoactive. The anatase (101) surface attracts more
      attention since it has lower surface energy relative to (001) and (100) surfaces
      and it is observed to adsorb small molecules on its surface. Using density
      functional theory (DFT) with on-site Coulomb interactions corrections, we have
      computed the structural and electronic properties of selected Au8 clusters
      interacting with clean and reduced anatase TiO2(101) surfaces. The computed
      adsorption energies are suggesting that the considered Au8 clusters are only
      physisorbed onto pristine TiO2(101) surface. Oxygen vacancies are found to
      enhance the absorption of Au8 on the Ti2(101) surface. Accurate simulations
      required spin polarized DFT since the ground state of Au8 interacting with
      defective TiO2(101) shows magnetic solutions. The results show that Au8 clusters
      are chemically bonded to the surface around the locality of the oxygen vacancy.
      The surface oxygen vacancy is found to be energetically more favourable than sub
      surface oxygen vacancy configuration. These vacancy sites may act as nucleation
      sites for small Au clusters or Au atoms. Finally, the computed electronic
      structure of all the Au8/TiO2(101) configurations considered in this work are
      analysed in the light of available experimental data. 

PMID- 25961527
TI  - Use of Quasi-SMILES and Monte Carlo Optimization to Develop Quantitative Feature
      Property/Activity Relationships (QFPR/QFAR) for Nanomaterials.
AB  - The CORAL software (http://www.insilico.eu/coral) has been used to develop
      quantitative feature-property/activity relationships (QFPRs/QFARs) for the
      prediction of endpoints related to different categories of nanomaterials. In
      contrast to previous models built up by using CORAL from a representation of the
      molecular structure by using simplified molecular input-line entry system
      (SMILES), the current QFPR/QFARs are based on an integrated representation of
      acting conditions (i.e., a combination of physicochemical and/or biochemical
      factors) of nanomaterials via the so-called quasi-SMILES notation. In contrast to
      traditional quantitative structure - property / activity relationships
      (QSPRs/QSARs), the new models are able to provide new insight on the conditions
      of acting of substances (e.g., chemicals and nanomaterials) independently of
      their molecular structure. The development and validation of the QFPR/QFAR models
      was carried out following the OECD principles. The statistical quality of models
      developed from quasi-SMILES is acceptable, with values for the determination
      coefficient in the range of 0.70 to 0.85 for various endpoints of environmental
      and human health relevance. Perspectives of the QFPR/QFAR and their interaction
      and overlapping with traditional QSPR/QSAR are also discussed. 

PMID- 25961528
TI  - Predicting Cell Association of Surface-Modified Nanoparticles Using Protein
      Corona Structure - Activity Relationships (PCSAR).
AB  - Nanoparticles are likely to interact in real-case application scenarios with
      mixtures of proteins and biomolecules that will absorb onto their surface forming
      the so-called protein corona. Information related to the composition of the
      protein corona and net cell association was collected from literature for a
      library of surface-modified gold and silver nanoparticles. For each protein in
      the corona, sequence information was extracted and used to calculate
      physicochemical properties and statistical descriptors. Data cleaning and
      preprocessing techniques including statistical analysis and feature selection
      methods were applied to remove highly correlated, redundant and non-significant
      features. A weighting technique was applied to construct specific signatures that
      represent the corona composition for each nanoparticle. Using this basic set of
      protein descriptors, a new Protein Corona Structure-Activity Relationship (PCSAR)
      that relates net cell association with the physicochemical descriptors of the
      proteins that form the corona was developed and validated. The features that
      resulted from the feature selection were in line with already published
      literature, and the computational model constructed on these features had a good
      accuracy (R(2)LOO=0.76 and R(2)LMO(25%)=0.72) and stability, with the advantage
      that the fingerprints based on physicochemical descriptors were independent of
      the specific proteins that form the corona. 

PMID- 25961529
TI  - Editorial: From Chemoinformatics to Nanoinformatics: New Tools for Drug Discovery
      and Nanoparticles Design in Medicinal Chemistry.

PMID- 25961530
TI  - High-Power Genuine Ultraviolet Light-Emitting Diodes Based On Colloidal
      Nanocrystal Quantum Dots.
AB  - Thin-film ultraviolet (UV) light-emitting diodes (LEDs) with emission wavelengths
      below 400 nm are emerging as promising light sources for various purposes, from
      our daily lives to industrial applications. However, current thin-film UV
      emitting devices radiate not only UV light but also visible light. Here, we
      introduce genuine UV-emitting colloidal nanocrystal quantum dot (NQD) LEDs
      (QLEDs) using precisely controlled NQDs consisting of a 2.5-nm-sized CdZnS
      ternary core and a ZnS shell. The effective core size is further reduced during
      the shell growth via the atomic diffusion of interior Cd atoms to the exterior
      ZnS shell, compensating for the photoluminescence red shift. This design enables
      us to develop CdZnS@ZnS UV QLEDs with pure UV emission and minimal parasitic
      peaks. The irradiance is as high as 2.0-13.9 mW cm(-2) at the peak wavelengths of
      377-390 nm, several orders of magnitude higher than that of other thin-film UV
      LEDs. 

PMID- 25961531
TI  - Platelet activation is a key event in the pathogenesis of streptococcal
      infections.
AB  - Diverse Streptococcus species including Streptococcus Pneumoniae, Sanguis,
      Gordonii, Mitis and Mutans cause life-threatening conditions including pneumonia,
      bacteremia and meningitis. These diseases bear a high morbidity and mortality and
      for this reason, understanding the key events in the pathogenesis of these
      infections have a great significance in their prevention and/or treatment. Here,
      we describe as how the activation of the platelets and their affinity to bind to
      bacterial proteins act as early key events in the pathogenesis of Streptococcal
      infections. 

PMID- 25961532
TI  - KIT gene mutations in gastrointestinal stromal tumor.
AB  - Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the
      gastrointestinal tract. It arises in the stomach, small intestine, colon, rectum
      and esophagus. KIT gene mutation is a feature of GIST, in addition to PDGFRA gene
      mutation. KIT gene mutations have been observed to be involved in the development
      of GIST, its recurrence after surgery and chemotherapy resistance in GIST. Exons
      13, 17, 9, and mainly exon 11 are concerned in these biological behaviors of
      GIST. In this review, we will discuss on the involvement of KIT gene mutations in
      the tumorigenesis, recurrence and chemotherapeutic resistance of GIST. 

PMID- 25961533
TI  - Systemic inflammation and multiple organ injury in traumatic hemorrhagic shock.
AB  - Traumatic hemorrhagic shock (HS) is a severe outcome of traumatic injury that
      accounts for numerous traumatic deaths. In the process of traumatic HS, both
      hemorrhage and trauma can trigger a complex cascade of posttraumatic events that
      are related to inflammatory and immune responses, which may lead to multiple
      organ injury or even death. From a mechanistic perspective, systemic inflammation
      and organ injury are involved coagulation, the complement system, impaired
      microcirculation and inflammatory signaling pathways. In this review, we discuss
      the systemic inflammation and multiple organ injury in post-traumatic HS. 

PMID- 25961534
TI  - The role of 14-3-3 proteins in gynecological tumors.
AB  - A large family of highly conserved cellular 14-3-3 proteins plays key roles in
      the regulation of central physiological pathways such as metabolism, protein
      trafficking, signal transduction, apoptosis and regulation of cell cycle. The
      involvement of these proteins in the regulation of various tumor suppressor genes
      and oncogenes points to their potential role in human cancer. According to some,
      the 14-3-3 proteins in gynecological tumors, promote gynecological tumors whereas
      others suggest that 14-3-3 proteins function as tumor suppressors in such tumors.
      Here, we review the use of 14-3-3 proteins as novel markers for screening and
      early diagnosis of gyncyological malignancies, and in monitoring the
      effectiveness of treatment. 14-3-3 proteins are proposed to be used as prognostic
      factors and as specific target in the treatment of cancers. 

PMID- 25961535
TI  - Epigenetic regulation of hepatic tumor-initiating cells.
AB  - Hepatocellular carcinoma (HCC) is the third most lethal cancer and resistant to
      common chemotherapy. Tumor-initiating cells (T-ICs) that are thought to be
      responsible for tumorigenesis share surface markers and signaling pathways
      similar to normal tissue stem cells. Identification of T-ICs and elucidation of
      aberrant epigenetic modulation and self-renewal pathways may provide new insights
      into hepatic carcinogenesis, metastasis and chemotherapeutic resistance. Histone
      modification, DNA methylation and microenvironmental changes are considered as
      key elements to promote the derivation and function of T-ICs. In this review, we
      intend to compare the similarity and difference between normal liver stem cells
      and T-ICs, and to define the intrinsic and micro-environmental factors that lead
      to the transformation from normal liver stem cells to hepatic T-ICs. We believe
      that etiology, microenvironmental alteration, epigenetic modification and
      epithelial-mesenchymal transition play a fundamental role in initiating the
      transformation. Strategies targeting signaling molecules critical in modulating
      these processes may offer a personalized therapy for HCC in the future. 

PMID- 25961536
TI  - Thymic derived iPs cells can be differentiated into cardiomyocytes.
AB  - Ventricular septal defect (VSD) is one of the common congenital heart
      malformations. Several factors lead to the development of VSD, including familial
      causes, exposure to certain drugs, infectious agents, and maternal metabolic
      disturbances. We considered that induced pluripotent stem (iPS) cells derived
      from VSD patients can be used to study the origin and pathogenesis of the VSD.
      Here, we show generation and cardiomyocyte differentiation potential of iPS cells
      from thymic epithelial cells of a patient with VSD (TECs-VSD) by overexpressing
      the four factors: OCT4, SOX2, NANOG, and LIN28 with lentiviral vectors. The self
      renewal and pluripotency of the VSD-iPS cells was verified in iPS cells by in
      vitro expression of pluripotency markers and formation of teratoma in vivo. iPS
      cell lines from VSD patients differentiated into functional cardiomyocytes can
      serve as a model system for studying the pathophysiology and identifying etiology
      of VSD. 

PMID- 25961537
TI  - Oxidized low-density lipoprotein alters endothelial progenitor cell populations.
AB  - Oxidized low-density lipoprotein (ox-LDL) is critical to atherosclerosis in
      hyperlipidemia. Bone marrow (BM)-derived endothelial progenitor cells (EPCs) are
      important to preventing atherosclerosis, and significantly decreased in
      hyperlipidemia. This study was to demonstrate ox-LDL and hyperlipidemia could
      exhibit similar effect on EPC population and the role of reactive oxygen species
      (ROS). ROS production in BM and blood was significantly increased in male C57BL/6
      mice with intravenous ox-LDL treatment, and in hyperlipidemic LDL receptor
      knockout mice with 4-month high-fat diet. ROS formation was effectively blocked
      with overexpression of antioxidant enzymes or N-acetylcysteine treatment. In
      hyperlipidemic and ox-LDL-treated mice, c-Kit(+)/CD31(+) cell number in BM and
      blood, and Sca-1(+)/Flk-1(+) cell number in blood, not in BM, were significantly
      decreased, which were not affected by inhibiting ROS production, while blood
      CD34(+)/Flk-1(+) cell number was significantly increased that was prevented with
      reduced ROS formation. However, blood CD34(+)/CD133(+) cell number increased in
      ox-LDL-treated mice, while decreased in hyperlipidemic mice. These data suggested
      that ox-LDL produced significant changes in BM and blood EPC populations similar
      (but not identical) to chronic hyperlipidemia with predominantly ROS-independent
      mechanism(s).

PMID- 25961538
TI  - L-arginine improves DNA synthesis in LPS-challenged enterocytes.
AB  - The neonatal small intestine is susceptible to damage by endotoxin, and this
      cytotoxicity may involve intracellular generation of reactive oxygen species
      (ROS), resulting in DNA damage and mitochondrial dysfunction. L-Arginine (Arg)
      confers a cytoprotective effect on lipopolysaccharide (LPS)-treated enterocytes
      through activation of the mammalian target of the rapamycin (mTOR) signaling
      pathway. Arg improves DNA synthesis and mitochondrial bioenergetics, which may
      also be responsible for beneficial effects of Arg on intestinal mucosal cells. In
      support of this notion, results of recent studies indicate that elevated Arg
      concentrations enhances DNA synthesis, cell-cycle progression, and mitochondrial
      bioenergetics in LPS-treated intestinal epithelial cells through mechanisms
      involving activation of the PI3K-Akt pathway. These findings provide a
      biochemical basis for dietary Arg supplementation to improve the regeneration and
      repair of the small-intestinal mucosa in both animals and humans. 

PMID- 25961539
TI  - Infantile haemangioma: a complicated disease.
AB  - Infantile haemangiomas (IH) are common benign vascular tumors of childhood. They
      are characterised by rapid growth during the first year of life and slow
      regression that is usually completed by 7-10 years of age. The underlying
      mechanism of action of IH is aberrant angiogenesis and vasculogenesis, and
      involves the mammalian target of rapamycin pathway and vascular endothelial
      growth factor pathway. IH become a challenge if they are part of a syndrome, are
      located in certain areas of the body, or if complications develop. The beta
      adrenergic receptor blocker propranolol is a promising new candidate for first
      line systemic therapy. This review focuses on the clinical characteristics,
      pathogenesis and management of IH. 

PMID- 25961540
TI  - Critical role of miRNAs in pancreatic cancer.
AB  - Pancreatic cancer (PC) is an aggressive malignancy with a high mortality rate and
      poor prognosis. Numerous investigations have shown that microRNA (miRNA) plays a
      vital role in PC. Thousands of miRNAs have been screened in PC and altered
      miRNAs, including circulating miRNAs, are associated with PC proliferation,
      apoptosis, metastasis, chemosensitivity, and radiosensitivity. Several studies
      have shown that miRNAs can act as potential diagnostic and prognostic markers.
      The present review focuses on recent advances regarding the roles of miRNAs in PC
      and their practical value. 

PMID- 25961541
TI  - Cell signaling in the interaction between pathogenic bacteria and immune cells.
AB  - Cell signaling is an essential part in the complex system of communication that
      governs basic cellular activities and coordinates cell actions. The ability of
      cells to perceive and correctly respond to their microenvironment is essential
      for cell survival and basic biological function. In the defense from pathogenic
      bacteria, the immune cells exert their function through various signaling
      pathways. In this review, we will summarize recent findings on the role of cell
      signaling in the interaction between pathogenic bacteria and immune cells,
      focusing on neutrophils and macrophages, which are part of the innate immunity,
      and also T cells, which are components of the adaptive immune system. 

PMID- 25961542
TI  - Identification of biomarkers for bone union promoted by mechanical stimulation.
AB  - At present, the identity of the proteins that participate in mechanical
      stimulation during the fracture healing process is not known. Here, we screened
      for and identified 299 proteins that are expressed in various stages of
      mechanically stimulated fracture healing. Among these biomarkers, 54 proteins
      were differentially expressed during all three recovery time points. Gene
      ontology (GO) analysis and selected biomarker candidates were used to determine
      their involvement in biological processes required for mechanically stimulated
      healing. The levels of cofilin-1 and A2HSG protein were significantly upregulated
      in the forth week after fracture suggesting that that they play a role in
      mechanically stimulated fracture healing. 

PMID- 25961543
TI  - Expression of AQP3 protein in hAECs is regulated by Camp-PKA-CREB signalling
      pathway.
AB  - Previous studies by others and our group have demonstrated the expression of AQP3
      protein in human chorioamniotic membranes. Here, we investigated whether cyclic
      adenosine monophosphate (cAMP) up-regulation of aquaporin 3 (AQP3) protein
      expression in human amniotic epithelial cells (hAECs) is mediated by protein
      kinase A (PKA) dependent or independent pathway. Cells were treated with various
      concentrations of Forskolin, SP-cAMP, H-89 at various time intervals or optimal
      concentration of Forskolin in combination with H-89 in the blocking experiments.
      Forskolin significantly increased cAMP levels and the expression of PKA, p-CREB
      and AQP3. SP-cAMP had similar effects. H-89 inhibited PKA, p-CREB and AQP3
      protein expression, and attenuated the stimulatory effect of Forskolin. These
      results show that the AQP3 protein expression in hAECs was regulated by cAMP-PKA
      CREB signal pathway. A relatively short biological half life of AQP3 renders its
      rapid responsiveness to regulation. 

PMID- 25961544
TI  - Role of microRNAs in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third
      leading cause of cancer related death worldwide. HCC develops through a multistep
      process that involves genetic and epigenetic changes. In addition to genetic and
      epigenetic mechanisms, recent studies have shown that microRNAs (miRNAs) play
      essential roles in hepatocellular carcinogenesis through the post-transcriptional
      regulation of tumor associated-genes. In this review, we summarize the role of
      miRNAs in HCC and its microenvironment, and discuss the implications for HCC
      therapy. 

PMID- 25961545
TI  - The role of BRAF in the pathogenesis of thyroid carcinoma.
AB  - BRAF is a cytoplasmic serine-threonine protein kinasethat plays a critical role
      in the MAPK signaling pathway. BRAF is the only member of the RAF family
      activated by mutation in human cancers. A single amino acid substitution (V600E)
      accounts for a multitude of human cancers, which causes constitutive kinase
      activity. In papillary thyroid cancer (PTC) and papillary-derived anaplastic
      thyroid cancer (ATC), the BRAF(V600E) mutation promotes follicular cell
      transformation. The BRAF(V600E)mutation could provide valuable prognostic
      information for thyroid cancer, because this mutation has been correlated with
      more aggressive and iodine-resistant phenotypes. Evidence has also shown that the
      detection of the BRAF(V600E) mutation in cancer is crucial in order to identify
      novel avenues for thyroid cancer treatment.Based on the BRAF kinase structure,
      novel drugs can potentially be designed to target oncogenic BRAF in cancer
      therapeutics. This review will focus on the recent progress in understandingthe
      functions of BRAF, the role of the BRAF mutations in thyroid carcinoma, and the
      correlation between BRAF mutations and cancer microenvironment. 

PMID- 25961546
TI  - A Monte Carlo simulation dissecting quantal release at the calyx of Held.
AB  - Although quantal release provides a basic control of synaptic strength, its
      underlying mechanisms remain unclear. Here, we report a refined realistic 3D
      vesicle fusion model at calyx-type synapses. By refining the micro ultrastructure
      and combining updated parameters, our model is appropriate for simulating quantal
      release. First, we confirmed the existence of kiss-and-run fusion and gave a
      justified estimation of its percentage in spontaneous and stimulated release.
      Second, we found the location of AMPA receptors caused the huge variation in the
      mEPSC rise time. Third, glutamate spillover only slightly contributed to the
      mEPSC decay time in small vesicles but caused a dual-peak event in large
      vesicles. Fourth, mEPSC rise time increased with amplitude, suggesting the
      contribution of vesicle size, not glutamate concentration. We also applied our
      model to the analysis of KCl, CaCl2 and synaptotagmin-2 triggered exocytosis. KCl
      globally accelerated the mEPSCs, whereas mEPSCs were slowed down in high calcium
      treatments and synaptotagmin-2 knock-out mice, indicating more kiss-and-run
      release. In summary, our model provides a convenient method for exploring the
      detailed mechanism of vesicle fusion. 

PMID- 25961547
TI  - MicroRNAs in colorectal cancer: potential biomarkers and therapeutic targets.
AB  - Colorectal Cancer (CRC) is one of the most common malignant tumors of
      gastrointestinal tract. The occurrence, development, diagnosis and prognosis have
      become a hot topic in current clinical research. However, current diagnosis and
      treatment still depend on the results of tumor imaging or pathology test.
      Therefore, to reveal the biological pathogenesis of CRC and to discover specific
      biomarkers for early diagnosis and better prognosis assessment of CRC have become
      key roles in current studies. Recent literature has revealed that aberrant
      expression of microRNAs (miRNAs) could contribute to the development and
      progression of CRC through the regulation of several critical pathways, including
      apoptosis, epithelial-mesenchymal transition, angiogenesis and signal
      transduction. These findings have also indicated that miRNAs could be a novel
      biomarker for early clinical diagnosis and prognosis evaluation of CRC. In this
      review, we have summarized the recent studies of miRNAs on the diagnosis,
      treatment and prognosis clinical biomarker of CRC. We also discussed the
      regulatory mechanisms of miRNAs in CRC, which may guide the future treatment for
      CRC. 

PMID- 25961548
TI  - Glioma: an overview of current classifications, characteristics, molecular
      biology and target therapies.
AB  - Glioma is the most common primary brain tumor, accounting for 30% to 40% of all
      intracranial tumors. About half of all gliomas in adults are glioblastomas.
      Patients with glioblastoma have a poor prognosis, with a median survival of one
      year despite aggressive therapy and a five year mortality of over 95%. Although
      considerable progress has been made in the technical proficiencies of surgical
      and radiation oncology, the overall impact of these advances on clinical outcomes
      has been disappointing. Recent elucidation of several biochemical and molecular
      markers associated with glioma may provide valuable insight into the underlying
      biological features of the disease, as well as illuminate possible new
      therapeutic targets. This review focuses on the current characteristics,
      classifications, and management of glioma. 

PMID- 25961551
TI  - MMP Inhibitors: Past, present and future.
AB  - Development of inhibitors of matrix metalloproteinases (MMPs) has been fraught
      with challenges. Early compounds largely failed due to poor selectivity and
      bioavailability. Dose-limiting side effects, off-target interactions, and
      improperly designed clinical trials significantly impeded clinical success. As
      information becomes available and technology evolves, tools to combat these
      obstacles have been developed. Improved methods for high throughput screening and
      drug design have led to identification of compounds exhibiting high potency,
      binding affinity, and favorable pharmacokinetic profiles. Current research into
      MMP inhibitors employs innovative approaches for drug delivery methods and
      allosteric inhibitors. Such innovation is key for development of clinically
      successful compounds. 

PMID- 25961552
TI  - NOK mediated mitogenic signaling is altered by P203L and V395I mutations.
AB  - The novel oncogene with kinase-domain (NOK), is an atypical receptor protein
      tyrosine kinase with potent oncogenic potential. In the current study, we
      generated two point mutations (P203L and V395I) on NOK gene. NOK(P203L) is
      identical to serine/threonine/tyrosine kinase 1 (STYK1), the aliases of NOK,
      while the V395I mutation was recovered from human glioblastoma. Both mutations
      did not impair NOK kinase activities, but V395I inhibited NOK
      autophosphorylation. Although with overall inhibition, both STYK1 and V395I
      affected the activities of extracellular regulated protein kinase (ERK), Akt and
      signal transducer and activator of transcription (STAT) differently in HEK293T
      cells versus HeLa and BaF3 stable cells The proliferation potentials for both
      STYK1 and V395I were significantly inhibited. Single mutation at either site was
      sufficient to abolish the IL-3 independent growth and the anchor-independent
      growth of of BaF3 stable cells. Overall, our data indicates that both P203 and
      V395 residues on NOK are important for NOK mediated mitogenic signaling, and the
      substitutions of P203L and V395I may selectively affect certain mitogenic
      signaling cascades in a tissue specific manner. 

PMID- 25961549
TI  - Tryptophan-kynurenine pathway is dysregulated in inflammation, and immune
      activation.
AB  - The kynurenine (Kyn) pathway is the major route for tryptophan (Trp) metabolism,
      and it contributes to several fundamental biological processes. Trp is
      constitutively oxidized by tryptophan 2, 3-dioxygenase in liver cells. In other
      cell types, it is catalyzed by an alternative inducible indoleamine-pyrrole 2, 3
      dioxygenase (IDO) under certain pathophysiological conditions, which consequently
      increases the formation of Kyn metabolites. IDO is up-regulated in response to
      inflammatory conditions as a novel marker of immune activation in early
      atherosclerosis. Besides, IDO and the IDO-related pathway are important mediators
      of the immunoinflammatory responses in advanced atherosclerosis. In particular,
      Kyn, 3-hydroxykynurenine, and quinolinic acid are positively associated with
      inflammation, oxidative stress (SOX), endothelial dysfunction, and carotid artery
      intima-media thickness values in end-stage renal disease patients. Moreover, IDO
      is a potential novel contributor to vessel relaxation and metabolism in systemic
      infections, which is also activated in acute severe heart attacks. The Kyn
      pathway plays a key role in the increased prevalence of cardiovascular disease by
      regulating inflammation, SOX, and immune activation. 

PMID- 25961550
TI  - Matrix metalloproteinases as breast cancer drivers and therapeutic targets.
AB  - Members of the matrix metalloproteinase (MMP) family have been identified as poor
      prognosis markers for breast cancer patients and as drivers of many facets of the
      tumor phenotype in experimental models. Early enthusiasm for MMPs as therapeutic
      targets was tempered following disappointing clinical trials that utilized broad
      spectrum, small molecule catalytic site inhibitors. However, subsequent research
      has continued to define key roles for MMPs as breast cancer promoters, to
      elucidate the complex roles that that these proteins play in breast cancer
      development and progression, and to identify how these roles are linked to
      specific and unique biochemical features of individual members of the MMP family.
      Here, we provide an overview of the structural features of the MMPs, then discuss
      clinical studies identifying which MMP family members are linked with breast
      cancer development and new experimental studies that reveal how these specific
      MMPs may play unique roles in the breast cancer microenvironment. We conclude
      with a discussion of the most promising avenues for development of therapeutic
      agents capable of targeting the tumor-promoting properties of MMPs.

PMID- 25961553
TI  - Gene and splicing therapies for neuromuscular diseases.
AB  - Neuromuscular disorders (NMD) are heterogeneous group of genetic diseases
      characterized by muscle weakness and wasting. Duchenne Muscular dystrophy (DMD)
      and Spinal muscular atrophy (SMA) are two of the most common and severe forms in
      humans and although the molecular mechanisms of these diseases have been
      extensively investigated, there is currently no effective treatment. However, new
      gene-based therapies have recently emerged with particular noted advances in
      using conventional gene replacement strategies and RNA-based technology. Whilst
      proof of principle have been demonstrated in animal models, several clinical
      trials have recently been undertaken to investigate the feasibility of these
      strategies in patients. In particular, antisense mediated exon skipping has shown
      encouraging results and hold promise for the treatment of dystrophic muscle. In
      this review, we summarize the recent progress of therapeutic approaches to
      neuromuscular diseases, with an emphasis on gene therapy and splicing modulation
      for DMD and SMA, focusing on the advantages offered by these technologies but
      also their challenges. 

PMID- 25961554
TI  - Lactic dehydrogenase and cancer: an overview.
AB  - Despite the intense scientific efforts made, there are still many tumors that are
      difficult to treat and the percentage of patient survival in the long-term is
      still too low. Thus, new approaches to the treatment of cancer are needed. Cancer
      is a highly heterogeneous and complex disease, whose development requires a
      reorganization of cell metabolism. Most tumor cells downregulate mitochondrial
      oxidative phosphorylation and increase the rate of glucose consumption and
      lactate release, independently of oxygen availability (Warburg effect). This
      metabolic rewiring is largely believed to favour tumor growth and survival,
      although the underlying molecular mechanisms are not completely understood.
      Importantly, the correlation between the aerobic glycolysis and cancer is widely
      regarded as a useful biochemical basis for the development of novel anticancer
      strategies. Among the enzymes involved in glycolysis, lactate dehydrogenase (LDH)
      is emerging as a very attractive target for possible pharmacological approaches
      in cancer therapy. This review addresses the state of the art and the
      perspectives concerning LDH both as a useful diagnostic marker and a relevant
      molecular target in cancer therapy and management. 

PMID- 25961555
TI  - ALK-mediated post-transcriptional regulation: focus on RNA-binding proteins.
AB  - Extensive research has been carried out in the past two decades to provide
      insights into the molecular mechanisms by which the Nucleophosmin-Anaplastic
      Lymphoma Kinase (NPM-ALK) exerts its oncogenic effects. These studies led to the
      concept that NPM-ALK acts at the transcriptional level through the activation of
      several transcription factors downstream of many different signaling pathways
      including JAK3/STAT3, PI3K/AKT and RAS/ERK. Nevertheless, the discovery of
      several RNA-binding proteins (RBPs) within ALK interactome suggested an
      additional and complementary role of this oncogenic kinase at the post
      transcriptional level. This review gives emerging views in ALK-mediated post
      transcriptional regulation with a focus on RBPs that are associated with ALK. We
      will summarize the capacity of NPM-ALK in modulating the biological properties of
      RBPs and then discuss the role of cytoplasmic aggregates, called AGs for "ALK
      granules", which are observed in anaplastic large cell lymphoma (ALCL) expressing
      the ALK kinase. AGs contain polyadenylated mRNAs and numerous RBPs but are
      distinct from processing bodies (PBs) and stress granules (SGs), two well-known
      discrete cytoplasmic sites involved in mRNA fate. 

PMID- 25961556
TI  - Heparin defends against the toxicity of circulating histones in sepsis.
AB  - Although circulating histones were demonstrated as major mediators of death in
      septic mice models, their roles in septic patients are not clarified. The present
      study sought to evaluate the clinical relevance of the circulating histone levels
      in septic children, and the antagonizing effects of heparin on circulating
      histones. Histone levels in the plasma of septic children were significantly
      higher than healthy controls, and positively correlated with disease severity.
      Histone treatment could activate NF-kappaB pathway of the endothelial cells and
      induce the secretion of large amount of cytokines that further amplify
      inflammation, subsequently leading to organ damage. Co-injection of low dose
      heparin with lethal dose histones could protect mouse from organ damage and death
      by antagonizing circulating histones, and similar effects were also observed in
      other septic models. Collectively, these findings indicated that circulating
      histones might serve as key factors in the pathogenesis of sepsis and their
      levels in plasma might be a marker for disease progression and prognosis.
      Furthermore, low dose heparin might be an effective therapy to hamper sepsis
      progression and reduce the mortality. 

PMID- 25961557
TI  - Root-Derived Short-Chain Suberin Diacids from Rice and Rape Seed in a Paddy Soil
      under Rice Cultivar Treatments.
AB  - Suberin-derived substituted fatty acids have been shown to be potential
      biomarkers for plant-derived carbon (C) in soils across ecosystems. Analyzing
      root derived suberin compounds bound in soil could help to understand the root
      input into a soil organic carbon pool. In this study, bound lipids were extracted
      and identified in root and topsoil samples. Short-chain suberin diacids were
      quantified under rice (Oryza sativa L.) and rape (Brassica campestris) rotations
      with different cultivar combinations in a Chinese rice paddy. After removal of
      free lipids with sequential extraction, the residual bound lipids were obtained
      with saponification and derivatization before analysis using gas chromatography
      mass spectrometry (GC-MS). Diacids C16 and C18 in bound lipids were detected both
      in rice and rape root samples, while diacids C20 and C22 were detected only in
      rape root samples. Accordingly, diacids were quantified in both rhizosphere and
      bulk soil (0-15 cm). The amount of total root-derived diacids in bulk soil varied
      in a range of 5.6-9.6 mg/kg across growth stages and crop seasons. After one year
      round rice-rape rotation, root-derived suberin diacids were maintained at a level
      of 7-9 mg/kg in bulk soil; this was higher under a super rice cultivar LY than
      under a hybrid cultivar IIY. While concentrations of the analyzed diacids were
      generally higher in rhizosphere than in bulk soil, the total diacid (DA)
      concentration was higher at the time of rape harvest than at rice harvest,
      suggesting that rape roots made a major contribution to the preservation of
      diacids in the paddy. Moreover, the net change in the concentration and the
      ratios of C16:0 DA to C18:1 DA, and of C16:0 DA to C18:0 DA, over a whole growing
      season, were greater under LY than under IIY, though there was no difference
      between cultivars within a single growth stage. Overall, total concentration of
      root-derived suberin diacids was found to be positively correlated to soil
      organic carbon concentration both for bulk soil and rhizosphere. However, the
      turnover and preservation of the root suberin biomolecules with soil property and
      field conditions deserve further field studies. 

PMID- 25961558
TI  - Use of cystatin C and serum creatinine for the diagnosis of contrast-induced
      nephropathy in patients undergoing contrast-enhanced computed tomography at an
      oncology centre.
AB  - OBJECTIVE: Our aim was to assess renal function using as laboratory measurements
      serum creatinine and cystatin C concentrations before and after administration of
      low-osmolarity (nonionic) iodinated contrast medium in patients with cancer
      undergoing computed tomography (CT). METHODS: This prospective study included 400
      oncologic outpatients. Serum creatinine and cystatin C concentrations were
      measured before and 72 h after contrast administration. Glomerular filtration
      rates (GFRs) were estimated using serum creatinine-based [Modification of Diet in
      Renal Disease (MDRD) and Cockroft-Gault and cystatin C based (Larsson) equations.
      Exploratory data analysis was performed. The nonparametric Wilcoxon test was used
      to compare pre and post contrast of test results and estimated clearance. The
      confidence interval used in the analysis was 95%. RESULTS: Compared with the pre
      contrast values, the mean serum creatinine concentration was significantly higher
      and average GFRs estimated using MDRD and Cockcroft-Gault equations were
      significantly lower after the administration of contrast (p <0.001). It was also
      observed a significant increase after contrast in the concentration of Cystatin C
      (p = 0.015). In addition, a decrease in GFR estimated using the average Larsson
      (p = 0.021) was observed between time points. However, none of the patients
      presented clinically significant nephropathy. CONCLUSIONS: Assessment using serum
      creatinine and cystatin C concentrations showed changes in renal function among
      patients with cancer undergoing contrast-enhanced CT examination in this study.
      No significant renal damage related to the use of low-osmolarity iodinated
      contrast medium of the type and dosage employed in this study was observed. This
      contrast medium is thus safe for use in patients with cancer.

PMID- 25961559
TI  - Immune Reconstitution Kinetics following Intentionally Induced Mixed Chimerism by
      Nonmyeloablative Transplantation.
AB  - Establishing mixed chimerism is a promising approach for inducing donor-specific
      transplant tolerance. The establishment and maintenance of mixed chimerism may
      enable long-term engraftment of organ transplants while minimizing the use of
      immunosuppressants. Several protocols for inducing mixed chimerism have been
      reported; however, the exact mechanism underlying the development of immune
      tolerance remains to be elucidated. Therefore, understanding the kinetics of
      engraftment during early post-transplant period may provide insight into
      establishing long-term mixed chimerism and permanent transplant tolerance. In
      this study, we intentionally induced allogeneic mixed chimerism using a
      nonmyeloablative regimen by host natural killer (NK) cell depletion and T cell
      depleted bone marrow (BM) grafts in a major histocompatibility complex (MHC)
      mismatched murine model and analyzed the kinetics of donor (C57BL/6) and
      recipient (BALB/c) engraftment in the weeks following transplantation. Donor BM
      cells were well engrafted and stabilized without graft-versus-host disease (GVHD)
      as early as one week post-bone marrow transplantation (BMT). Donor-derived thymic
      T cells were reconstituted four weeks after BMT; however, the emergence of newly
      developed T cells was more obvious at the periphery as early as two weeks after
      BMT. Also, the emergence and changes in ratio of recipient- and donor-derived NKT
      cells and antigen presenting cells (APCs) including dendritic cells (DCs) and B
      cells were noted after BMT. Here, we report a longitudinal analysis of the
      development of donor- and recipient-originated hematopoietic cells in various
      lymphatic tissues of intentionally induced mixed chimerism mouse model during
      early post-transplant period. Through the understanding of immune reconstitution
      at early time points after nonmyeloablative BMT, we suggest guidelines on
      intentionally inducing durable mixed chimerism. 

PMID- 25961560
TI  - The Amino Acid Arginine 210 of the Response Regulator HrpG of Xanthomonas citri
      subsp. citri Is Required for HrpG Function in Virulence.
AB  - Xanthomonas citri subsp. citri colonizes its hosts through the trafficking of
      effector proteins to the plant cell by the type III protein secretion system. In
      X. citri subsp. citri, as in other plant pathogens, the hrp cluster encodes the
      type III protein secretion system and is regulated by the transcription factors
      HrpG and HrpX. HrpG belongs to the OmpR family's response regulator of EnvZ/OmpR
      two-component signal transduction system. Here, we show that the arginine 210
      residue is crucial for the transcriptional activity of HrpG revealed by the
      absence of disease in host plants and hypersensitive response in non-host plants
      when a strain carrying this point mutation is used in plant infiltration assays.
      Also, this strain showed decreased expression levels of hrp genes in bacteria
      grown in culture or when they were recovered from citrus leaves. Moreover, we
      show for the first time that HrpG binds to both hrpX and its own promoter, and
      the change of the arginine 210 by a cysteine does not prevent the binding to both
      promoters. Nevertheless, in vitro hrpX transcription was observed only with HrpG
      whereas no transcription was detected with the R210C mutant. HrpG was able to
      interact with itself as well as with the mutant R210C suggesting that it
      functions as a dimer. The mutant protein R210C showed altered protease
      sensitivity, suggesting that Arg210 is essential for protein active conformation
      and thus for transcriptional activity. Our results indicate that arginine 210 in
      HrpG, as it may occur with this conserved residue in other members of this family
      of response regulators, is not required for DNA binding whereas is essential for
      hrp genes transcription and therefore for pathogenicity and HR induction. 

PMID- 25961561
TI  - The discrete multi-hybrid system for the simulation of solid-liquid flows.
AB  - This study proposes a model based on the combination of Smoothed Particle
      Hydrodynamics, Coarse Grained Molecular Dynamics and the Discrete Element Method
      for the simulation of dispersed solid-liquid flows. The model can deal with a
      large variety of particle types (non-spherical, elastic, breakable, melting,
      solidifying, swelling), flow conditions (confined, free-surface, microscopic),
      and scales (from microns to meters). Various examples, ranging from biological
      fluids to lava flows, are simulated and discussed. In all cases, the model
      captures the most important features of the flow. 

PMID- 25961562
TI  - Field evidence of social influence in the expression of political preferences:
      the case of secessionists flags in Barcelona.
AB  - Models of social influence have explored the dynamics of social contagion,
      imitation, and diffusion of different types of traits, opinions, and conducts.
      However, few behavioral data indicating social influence dynamics have been
      obtained from direct observation in "natural" social contexts. The present
      research provides that kind of evidence in the case of the public expression of
      political preferences in the city of Barcelona, where thousands of citizens
      supporting the secession of Catalonia from Spain have placed a Catalan flag in
      their balconies and windows. Here we present two different studies. 1) During
      July 2013 we registered the number of flags in 26% of the electoral districts in
      the city of Barcelona. We find that there is a large dispersion in the density of
      flags in districts with similar density of pro-independence voters. However, by
      comparing the moving average to the global mean we find that the density of flags
      tends to be fostered in electoral districts where there is a clear majority of
      pro-independence vote, while it is inhibited in the opposite cases. We also show
      that the distribution of flags in the observed districts deviates significantly
      from that of an equivalent random distribution. 2) During 17 days around
      Catalonia's 2013 national holiday we observed the position at balcony resolution
      of the flags displayed in the facades of a sub-sample of 82 blocks. We compare
      the 'clustering index' of flags on the facades observed each day to thousands of
      equivalent random distributions. Again we provide evidence that successive
      hangings of flags are not independent events but that a local influence mechanism
      is favoring their clustering. We also find that except for the national holiday
      day the density of flags tends to be fostered in facades located in electoral
      districts where there is a clear majority of pro-independence vote. 

PMID- 25961563
TI  - Trend Patterns of Vegetative Coverage and Their Underlying Causes in the Deserts
      of Northwest China over 1982-2008.
AB  - We identified the spatiotemporal patterns of the Normalized Difference Vegetation
      Index (NDVI) for the years 1982-2008 in the desert areas of Northwest China and
      quantified the impacts of climate and non-climate factors on NDVI changes. The
      results indicate that although the mean NDVI has improved in 24.7% of the study
      region; 16.3% among the region has been stagnating in recent years and only 8.4%
      had a significantly increasing trend. Additionally, 45.3% of the region has
      maintained a stable trend over the study period and 30.0% has declined. A
      multiple regression model suggests that a wetter climate (quantified by the
      Palmer Drought Severity Index, PDSI) is associated with higher NDVI in most areas
      (18.1% of significance) but these historical changes in PDSI only caused an
      average improvement of approximately 0.4% over the study region. Contrasting the
      regression results under different trend patterns, no significant differences in
      PDSI impacts were detected among the four trend patterns. Therefore, we conclude
      that climate is not the primary driver for vegetative coverage in Northwest
      China. Future studies will be required to identify the impacts of specific non
      climatic factors on vegetative coverage based on high-resolution data, which will
      be beneficial in creating an effective strategy to combat the recent
      desertification trend in China. 

PMID- 25961565
TI  - Asymmetric Paper Supercapacitor Based on Amorphous Porous Mn3O4 Negative
      Electrode and Ni(OH)2 Positive Electrode: A Novel and High-Performance Flexible
      Electrochemical Energy Storage Device.
AB  - Here we synthesize novel asymmetric all-solid-state paper supercapacitors (APSCs)
      based on amorphous porous Mn3O4 grown on conducting paper (NGP) (Mn3O4/NGP)
      negative electrode and Ni(OH)2 grown on NGP (Ni(OH)2/NGP) as positive electrode,
      and they have attracted intensive research interest owing to their outstanding
      properties such as being flexible, ultrathin, and lightweight. The fabricated
      APSCs exhibit a high areal Csp of 3.05 F/cm3 and superior cycling stability. The
      novel asymmetric APSCs also exhibit high energy density of 0.35 mW h/cm3, high
      power density of 32.5 mW/cm3, and superior cycling performance (<17% capacitance
      loss after 12,000 cycles at a high scan rate of 100 mV/s). This work shows the
      first example of amorphous porous metal oxide/NGP electrodes for the asymmetric
      APSCs, and these systems hold great potential for future flexible electronic
      devices.

PMID- 25961564
TI  - Epidemiology of HIV among US Air Force Military Personnel, 1996-2011.
AB  - OBJECTIVE: The objectives of this study were to describe the epidemiology of HIV
      in the United States Air Force (USAF) from 1996 through 2011 and to assess
      whether socio-demographic characteristics and service-related mobility, including
      military deployments, were associated with HIV infection. METHODS: We conducted a
      retrospective cohort analysis of USAF personnel who were HIV-infected during the
      study period January 1, 1996 through December 31, 2011 and a matched case-control
      study. Cases were USAF personnel newly-diagnosed with HIV during the study
      period. Five randomly-selected HIV-uninfected controls were matched to each case
      by age, length of service, sex, race, service, component, and HIV test collection
      date. Socio-demographic and service-related mobility factors and HIV diagnosis
      were assessed using conditional logistic regression. RESULTS: During the study
      period, the USAF had 541 newly diagnosed HIV-infected cases. HIV incidence rate
      (per 100,000 person-years) among 473 active duty members was highest in 2007
      (16.78), among black/ African-American USAF members (26.60) and those aged 25 to
      29 years (10.84). In unadjusted analysis restricted to personnel on active duty,
      10 characteristics were identified and considered for final multivariate
      analysis. Of these single (adjusted odds ratio [aOR], 8.15, 95% confidence
      interval [CI] 5.71-11.6) or other marital status (aOR 4.60, 95% CI 2.72-7.75),
      communications/ intelligence (aOR 2.57, 95% CI 1.84-3.60) or healthcare (aOR
      2.07, 95% CI 1.28-3.35) occupations, and having no deployment in the past 2 years
      before diagnosis (aOR 2.02, 95% CI 1.47-2.78) conferred higher odds of HIV
      infection in adjusted analysis. CONCLUSION: The highest risk of HIV infection in
      the USAF was among young unmarried deployment-naive males, especially those in
      higher risk occupation groups. In an era when worldwide military operations have
      increased, these analyses identified potential areas where targeted HIV
      prevention efforts may be beneficial in reducing HIV incidence in the USAF
      military population.

PMID- 25961566
TI  - Chronic Inhibition of PDE5 Limits Pro-Inflammatory Monocyte-Macrophage
      Polarization in Streptozotocin-Induced Diabetic Mice.
AB  - Diabetes mellitus is characterized by changes in endothelial cells that alter
      monocyte recruitment, increase classic (M1-type) tissue macrophage infiltration
      and lead to self-sustained inflammation. Our and other groups recently showed
      that chronic inhibition of phosphodiesterase-5 (PDE5i) affects circulating
      cytokine levels in patients with diabetes; whether PDE5i also affects circulating
      monocytes and tissue inflammatory cell infiltration remains to be established.
      Using murine streptozotocin (STZ)-induced diabetes and in human vitro cell-cell
      adhesion models we show that chronic hyperglycemia induces changes in myeloid and
      endothelial cells that alter monocyte recruitment and lead to self-sustained
      inflammation. Continuous PDE5i with sildenafil (SILD) expanded tissue anti
      inflammatory TIE2-expressing monocytes (TEMs), which are known to limit
      inflammation and promote tissue repair. Specifically, SILD: 1) normalizes the
      frequency of circulating pro-inflammatory monocytes triggered by hyperglycemia
      (53.7 +/- 7.9% of CD11b+Gr-1+ cells in STZ vs. 30.4 +/- 8.3% in STZ+SILD and 27.1
      +/- 1.6% in CTRL, P<0.01); 2) prevents STZ-induced tissue inflammatory
      infiltration (4-fold increase in F4/80+ macrophages in diabetic vs. control mice)
      by increasing renal and heart anti-inflammatory TEMs (30.9 +/- 3.6% in STZ+SILD
      vs. 6.9 +/- 2.7% in STZ, P <0.01, and 11.6 +/- 2.9% in CTRL mice); 3) reduces
      vascular inflammatory proteins (iNOS, COX2, VCAM-1) promoting tissue protection;
      4) lowers monocyte adhesion to human endothelial cells in vitro through the TIE2
      receptor. All these changes occurred independently from changes of glycemic
      status. In summary, we demonstrate that circulating renal and cardiac TEMs are
      defective in chronic hyperglycemia and that SILD normalizes their levels by
      facilitating the shift from classic (M1-like) to alternative (M2-like)/TEM
      macrophage polarization. Restoration of tissue TEMs with PDE5i could represent an
      additional pharmacological tool to prevent end-organ diabetic complications. 

PMID- 25961567
TI  - West Nile virus positive blood donation and subsequent entomological
      investigation, Austria, 2014.
AB  - The detection of West Nile virus (WNV) nucleic acid in a blood donation from
      Vienna, Austria, as well as in Culex pipiens pupae and egg rafts, sampled close
      to the donor's residence, is reported. Complete genomic sequences of the human-
      and mosquito-derived viruses were established, genetically compared and
      phylogenetically analyzed. The viruses were not identical, but closely related to
      each other and to recent Czech and Italian isolates, indicating co-circulation of
      related WNV strains within a confined geographic area. The detection of WNV in a
      blood donation originating from an area with low WNV prevalence in humans (only
      three serologically diagnosed cases between 2008 and 2014) is surprising and
      emphasizes the importance of WNV nucleic acid testing of blood donations even in
      such areas, along with active mosquito surveillance programs. 

PMID- 25961568
TI  - The temporal expression pattern of alpha-synuclein modulates olfactory
      neurogenesis in transgenic mice.
AB  - BACKGROUND: Adult neurogenesis mirrors the brain's endogenous capacity to
      generate new neurons throughout life. In the subventricular zone/ olfactory bulb
      system adult neurogenesis is linked to physiological olfactory function and has
      been shown to be impaired in murine models of neuronal alpha-Synuclein
      overexpression. We analyzed the degree and temporo-spatial dynamics of adult
      olfactory bulb neurogenesis in transgenic mice expressing human wild-type alpha
      Synuclein (WTS) under the murine Thy1 (mThy1) promoter, a model known to have a
      particularly high tg expression associated with impaired olfaction. RESULTS:
      Survival of newly generated neurons (NeuN-positive) in the olfactory bulb was
      unchanged in mThy1 transgenic animals. Due to decreased dopaminergic
      differentiation a reduction in new dopaminergic neurons within the olfactory bulb
      glomerular layer was present. This is in contrast to our previously published
      data on transgenic animals that express WTS under the control of the human
      platelet-derived growth factor beta (PDGF) promoter, that display a widespread
      decrease in survival of newly generated neurons in regions of adult neurogenesis,
      resulting in a much more pronounced neurogenesis deficit. Temporal and
      quantitative expression analysis using immunofluorescence co-localization
      analysis and Western blots revealed that in comparison to PDGF transgenic
      animals, in mThy1 transgenic animals WTS is expressed from later stages of
      neuronal maturation only but at significantly higher levels both in the olfactory
      bulb and cortex. CONCLUSIONS: The dissociation between higher absolute expression
      levels of alpha-Synuclein but less severe impact on adult olfactory neurogenesis
      in mThy1 transgenic mice highlights the importance of temporal expression
      characteristics of alpha-Synuclein on the maturation of newborn neurons.

PMID- 25961569
TI  - Astragaloside IV Attenuates Glutamate-Induced Neurotoxicity in PC12 Cells through
      Raf-MEK-ERK Pathway.
AB  - Astragaloside IV (AGS-IV) is a main active ingredient of Astragalus membranaceus
      Bunge, a medicinal herb prescribed as an immunostimulant, hepatoprotective,
      antiperspirant, a diuretic or a tonic as documented in Chinese Materia Medica. In
      the present study, we employed a high-throughput comparative proteomic approach
      based on 2D-nano-LC-MS/MS to investigate the possible mechanism of action
      involved in the neuroprotective effect of AGS-IV against glutamate-induced
      neurotoxicity in PC12 cells. Differential proteins were identified, among which
      13 proteins survived the stringent filter criteria and were further included for
      functional discussion. Two proteins (vimentin and Gap43) were randomly selected,
      and their expression levels were further confirmed by western blots analysis. The
      results matched well with those of proteomics. Furthermore, network analysis of
      protein-protein interactions (PPI) and pathways enrichment with AGS-IV associated
      proteins were carried out to illustrate its underlying molecular mechanism.
      Proteins associated with signal transduction, immune system, signaling molecules
      and interaction, and energy metabolism play important roles in neuroprotective
      effect of AGS-IV and Raf-MEK-ERK pathway was involved in the neuroprotective
      effect of AGS-IV against glutamate-induced neurotoxicity in PC12 cells. This
      study demonstrates that comparative proteomics based on shotgun approach is a
      valuable tool for molecular mechanism studies, since it allows the simultaneously
      evaluate the global proteins alterations. 

PMID- 25961570
TI  - Chaperone-Mediated Autophagy Targets IFNAR1 for Lysosomal Degradation in Free
      Fatty Acid Treated HCV Cell Culture.
AB  - BACKGROUND: Hepatic steatosis is a risk factor for both liver disease progression
      and an impaired response to interferon alpha (IFN-alpha)-based combination
      therapy in chronic hepatitis C virus (HCV) infection. Previously, we reported
      that free fatty acid (FFA)-treated HCV cell culture induces hepatocellular
      steatosis and impairs the expression of interferon alpha receptor-1 (IFNAR1),
      which is why the antiviral activity of IFN-alpha against HCV is impaired. AIM: To
      investigate the molecular mechanism by which IFNAR1 expression is impaired in HCV
      cell culture with or without free fatty acid-treatment. METHOD: HCV-infected Huh
      7.5 cells were cultured with or without a mixture of saturated (palmitate) and
      unsaturated (oleate) long-chain free fatty acids (FFA). Intracytoplasmic fat
      accumulation in HCV-infected culture was visualized by oil red staining.
      Clearance of HCV in FFA cell culture treated with type I IFN (IFN-alpha) and Type
      III IFN (IFN-lambda) was determined by Renilla luciferase activity, and the
      expression of HCV core was determined by immunostaining. Activation of Jak-Stat
      signaling in the FFA-treated HCV culture by IFN-alpha alone and IFN-lambda alone
      was examined by Western blot analysis and confocal microscopy. Lysosomal
      degradation of IFNAR1 by chaperone-mediated autophagy (CMA) in the FFA-treated
      HCV cell culture model was investigated. RESULTS: FFA treatment induced dose
      dependent hepatocellular steatosis and lipid droplet accumulation in HCV-infected
      Huh-7.5 cells. FFA treatment of infected culture increased HCV replication in a
      concentration-dependent manner. Intracellular lipid accumulation led to reduced
      Stat phosphorylation and nuclear translocation, causing an impaired IFN-alpha
      antiviral response and HCV clearance. Type III IFN (IFN-lambda), which binds to a
      separate receptor, induces Stat phosphorylation, and nuclear translocation as
      well as antiviral clearance in FFA-treated HCV cell culture. We show here that
      the HCV-induced autophagy response is increased in FFA-treated cell culture.
      Pharmacological inhibitors of lysosomal degradation, such as ammonium chloride
      and bafilomycin, prevented IFNAR1 degradation in FFA-treated HCV cell culture.
      Activators of chaperone-mediated autophagy, including 6-aminonicotinamide and
      nutrient starvation, decreased IFNAR1 levels in Huh-7.5 cells. Co
      immunoprecipitation, colocalization and siRNA knockdown experiments revealed that
      IFNAR1 but not IFNLR1 interacts with HSC70 and LAMP2A, which are core components
      of chaperone-mediated autophagy (CMA). CONCLUSION: Our study presents evidence
      indicating that chaperone-mediated autophagy targets IFNAR1 degradation in the
      lysosome in FFA-treated HCV cell culture. These results provide a mechanism for
      why HCV induced autophagy response selectively degrades type I but not the type
      III IFNAR1.

PMID- 25961572
TI  - A Comparison of Methods to Measure Fitness in Escherichia coli.
AB  - In order to characterize the dynamics of adaptation, it is important to be able
      to quantify how a population's mean fitness changes over time. Such measurements
      are especially important in experimental studies of evolution using microbes. The
      Long-Term Evolution Experiment (LTEE) with Escherichia coli provides one such
      system in which mean fitness has been measured by competing derived and ancestral
      populations. The traditional method used to measure fitness in the LTEE and many
      similar experiments, though, is subject to a potential limitation. As the
      relative fitness of the two competitors diverges, the measurement error increases
      because the less-fit population becomes increasingly small and cannot be
      enumerated as precisely. Here, we present and employ two alternatives to the
      traditional method. One is based on reducing the fitness differential between the
      competitors by using a common reference competitor from an intermediate
      generation that has intermediate fitness; the other alternative increases the
      initial population size of the less-fit, ancestral competitor. We performed a
      total of 480 competitions to compare the statistical properties of estimates
      obtained using these alternative methods with those obtained using the
      traditional method for samples taken over 50,000 generations from one of the LTEE
      populations. On balance, neither alternative method yielded measurements that
      were more precise than the traditional method. 

PMID- 25961571
TI  - Distinct effects of memory retrieval and articulatory preparation when learning
      and accessing new word forms.
AB  - Temporal and frontal activations have been implicated in learning of novel word
      forms, but their specific roles remain poorly understood. The present
      magnetoencephalography (MEG) study examines the roles of these areas in
      processing newly-established word form representations. The cortical effects
      related to acquiring new phonological word forms during incidental learning were
      localized. Participants listened to and repeated back new word form stimuli that
      adhered to native phonology (Finnish pseudowords) or were foreign (Korean words),
      with a subset of the stimuli recurring four times. Subsequently, a modified 1
      back task and a recognition task addressed whether the activations modulated by
      learning were related to planning for overt articulation, while parametrically
      added noise probed reliance on developing memory representations during effortful
      perception. Learning resulted in decreased left superior temporal and increased
      bilateral frontal premotor activation for familiar compared to new items. The
      left temporal learning effect persisted in all tasks and was strongest when
      stimuli were embedded in intermediate noise. In the noisy conditions, native
      phonotactics evoked overall enhanced left temporal activation. In contrast, the
      frontal learning effects were present only in conditions requiring overt
      repetition and were more pronounced for the foreign language. The results
      indicate a functional dissociation between temporal and frontal activations in
      learning new phonological word forms: the left superior temporal responses
      reflect activation of newly-established word-form representations, also during
      degraded sensory input, whereas the frontal premotor effects are related to
      planning for articulation and are not preserved in noise. 

PMID- 25961573
TI  - Human TM9SF4 Is a New Gene Down-Regulated by Hypoxia and Involved in Cell
      Adhesion of Leukemic Cells.
AB  - BACKGROUND: The transmembrane 9 superfamily protein member 4, TM9SF4, belongs to
      the TM9SF family of proteins highly conserved through evolution. TM9SF4 homologs,
      previously identified in many different species, were mainly involved in cellular
      adhesion, innate immunity and phagocytosis. In human, the function and biological
      significance of TM9SF4 are currently under investigation. However, TM9SF4 was
      found overexpressed in human metastatic melanoma and in a small subset of acute
      myeloid leukemia (AMLs) and myelodysplastic syndromes, consistent with an
      oncogenic function of this gene. PURPOSE AND RESULTS: In this study, we first
      analyzed the expression and regulation of TM9SF4 in normal and leukemic cells and
      identified TM9SF4 as a gene highly expressed in human quiescent CD34+
      hematopoietic progenitor cells (HPCs), regulated during monocytic and
      granulocytic differentiation of HPCs, both lineages giving rise to mature myeloid
      cells involved in adhesion, phagocytosis and immunity. Then, we found that TM9SF4
      is markedly overexpressed in leukemic cells and in AMLs, particularly in M2, M3
      and M4 AMLs (i.e., in AMLs characterized by the presence of a more or less
      differentiated granulocytic progeny), as compared to normal CD34+ HPCs.
      Proliferation and differentiation of HPCs occurs in hypoxia, a physiological
      condition in bone marrow, but also a crucial component of cancer
      microenvironment. Here, we investigated the impact of hypoxia on TM9SF4
      expression in leukemic cells and identified TM9SF4 as a direct target of HIF
      1alpha, downregulated in these cells by hypoxia. Then, we found that the hypoxia
      mediated downregulation of TM9SF4 expression is associated with a decrease of
      cell adhesion of leukemic cells to fibronectin, thus demonstrating that human
      TM9SF4 is a new molecule involved in leukemic cell adhesion. CONCLUSIONS:
      Altogether, our study reports for the first time the expression of TM9SF4 at the
      level of normal and leukemic hematopoietic cells and its marked expression at the
      level of AMLs displaying granulocytic differentiation.

PMID- 25961576
TI  - Correction: Parentage of overlapping offspring of an arboreal-breeding frog with
      no nest defense: implications for nest site selection and reproductive strategy.

PMID- 25961574
TI  - Suppression of the Insulin Receptors in Adult Schistosoma japonicum Impacts on
      Parasite Growth and Development: Further Evidence of Vaccine Potential.
AB  - To further investigate the importance of insulin signaling in the growth,
      development, sexual maturation and egg production of adult schistosomes, we have
      focused attention on the insulin receptors (SjIRs) of Schistosoma japonicum,
      which we have previously cloned and partially characterised. We now show, by
      Biolayer Interferometry, that human insulin can bind the L1 subdomain (insulin
      binding domain) of recombinant (r)SjIR1 and rSjIR2 (designated SjLD1 and SjLD2)
      produced using the Drosophila S2 protein expression system. We have then used RNA
      interference (RNAi) to knock down the expression of the SjIRs in adult S.
      japonicum in vitro and show that, in addition to their reduced transcription, the
      transcript levels of other important downstream genes within the insulin pathway,
      associated with glucose metabolism and schistosome fecundity, were also impacted
      substantially. Further, a significant decrease in glucose uptake was observed in
      the SjIR-knockdown worms compared with luciferase controls. In vaccine/challenge
      experiments, we found that rSjLD1 and rSjLD2 depressed female growth, intestinal
      granuloma density and faecal egg production in S. japonicum in mice presented
      with a low dose challenge infection. These data re-emphasize the potential of the
      SjIRs as veterinary transmission blocking vaccine candidates against zoonotic
      schistosomiasis japonica in China and the Philippines. 

PMID- 25961577
TI  - An Update on Maryland's All-Payer Approach to Reforming the Delivery of Health
      Care.

PMID- 25961575
TI  - The undiagnosed chronically-infected HCV population in France. Implications for
      expanded testing recommendations in 2014.
AB  - BACKGROUND: Recent HCV therapeutic advances make effective screening crucial for
      potential HCV eradication. To identify the target population for a possible
      population-based screening strategy to complement current risk-based testing in
      France, we aimed to estimate the number of adults with undiagnosed chronic HCV
      infection and age and gender distribution at two time points: 2004 and 2014.
      METHODS: A model taking into account mortality, HCV incidence and diagnosis rates
      was applied to the 2004 national seroprevalence survey. RESULTS: In 2014, an
      estimated 74,102 individuals aged 18 to 80 were undiagnosed for chronic HCV
      infection (plausible interval: 64,920-83,283) compared with 100,868 [95%CI:
      58,534-143,202] in 2004. Men aged 18-59 represented approximately half of the
      undiagnosed population in 2014. The proportion of undiagnosed individuals in 2004
      (43%) varied from 21.9% to 74.1% in the 1945-1965 and 1924-1944 birth cohorts.
      Consequently, age and gender distributions between the chronically-infected
      (diagnosed and undiagnosed) and undiagnosed HCV populations were different, the
      1945-1965 birth cohort representing 48.9% and 24.7%, respectively. CONCLUSIONS:
      Many individuals were still undiagnosed in 2014 despite a marked reduction with
      respect to 2004. The present work contributed to the 2014 recommendation of a new
      French complementary screening strategy, consisting in one-time simultaneous HCV,
      HBV and HIV testing in men aged 18-60. Further studies are needed to assess the
      cost-effectiveness and feasibility of such a strategy. We also demonstrated that
      data on the undiagnosed HCV population are crucial to help adapt testing
      strategies, as the features of the chronically-infected HCV population are very
      distinct.

PMID- 25961578
TI  - Epidemiology and prognosis of coagulase-negative staphylococcal endocarditis:
      impact of vancomycin minimum inhibitory concentration.
AB  - This study describes coagulase-negative staphylococcal (CoNS) infective
      endocarditis (IE) epidemiology at our institution, the antibiotic susceptibility
      profile, and the influence of vancomycin minimum inhibitory concentration (MIC)
      on patient outcomes. One hundred and three adults with definite IE admitted to an
      850-bed tertiary care hospital in Barcelona from 1995-2008 were prospectively
      included in the cohort. We observed that CoNS IE was an important cause of
      community-acquired and healthcare-associated IE; one-third of patients involved
      native valves. Staphylococcus epidermidis was the most frequent species,
      methicillin-resistant in 52% of patients. CoNS frozen isolates were available in
      88 patients. Vancomycin MICs of 2.0 MUg/mL were common; almost all cases were
      found among S. epidermidis isolates and did not increase over time. Eighty-five
      patients were treated either with cloxacillin or vancomycin: 38 patients (Group
      1) were treated with cloxacillin, and 47 received vancomycin; of these 47, 27 had
      CoNS isolates with a vancomycin MIC <2.0 MUg/mL (Group 2), 20 had isolates with a
      vancomycin MIC >= 2.0 MUg/mL (Group 3). One-year mortality was 21%, 48%, and 65%
      in Groups 1, 2, and 3, respectively (P = 0.003). After adjusting for confounders
      and taking Group 2 as a reference, methicillin-susceptibility was associated with
      lower 1-year mortality (OR 0.12, 95% CI 0.02-0.55), and vancomycin MIC >= 2.0
      MUg/mL showed a trend to higher 1-year mortality (OR 3.7, 95% CI 0.9-15.2;
      P=0.069). Other independent variables associated with 1-year mortality were heart
      failure (OR 6.2, 95% CI 1.5-25.2) and pacemaker lead IE (OR 0.1, 95%CI 0.02
      0.51). In conclusion, methicillin-resistant S.epidermidis was the leading cause
      of CoNS IE, and patients receiving vancomycin had higher mortality rates than
      those receiving cloxacillin; mortality was higher among patients having isolates
      with vancomycin MICs >= 2.0 MUg/mL.

PMID- 25961579
TI  - Inhibition of IL-6 signaling pathway by curcumin in uterine decidual cells.
AB  - IL-6 is a multifunctional pro-inflammatory cytokine and has been implicated in
      many gestational disorders including preterm birth. Currently, there are no
      appropriate therapeutic interventions available to circumvent inflammatory
      mediated gestational disorders. Therefore, the goal of this study was to identify
      a safe and effective pharmacological compound to counterbalance inflammatory
      responses in the uterus. Curcumin, a naturally-occurring polyphenolic compound,
      has been widely used in alternative medicine to treat inflammatory diseases.
      However, the anti-inflammatory effect of curcumin has not been explored in
      uterine decidual cells, a major source of IL-6. Therefore, we examined the effect
      of curcumin on IL-6 expression using two types of uterine decidual cells 1) HuF
      cells, primary human fibroblast cells obtained from the decidua parietalis; 2)
      UIII cells, a rodent non-transformed decidual cell line. Curcumin treatment
      completely abrogated the expression of IL-1beta-induced IL-6 in these cells.
      Curcumin also strongly inhibited the expression of gp130, a critical molecule in
      IL-6 signaling, whereas expression of IL-6R and sIL-6R was not affected. Curcumin
      also inhibited phosphorylation and nuclear localization of STAT3, a well-known
      downstream mediator of IL-6 signaling. Furthermore, curcumin attenuated IL-1beta
      induced IL-6 promoter reporter activity suggesting transcriptional regulation. To
      further understand whether NF-?B is involved in this inhibition, we examined the
      effect of curcumin on the expression of p50 and p65 subunits of NF-?B in decidual
      cells. Expression of IL-1beta-induced p50 mRNA was repressed by curcumin while
      p65 mRNA was not affected. However, curcumin treatment dramatically inhibited
      both p50 and p65 protein levels and prevented its nuclear localization. This
      effect is at least partly mediated through the deactivation of IKK, since IL
      1beta-induced IKKalpha/beta phosphorylation is decreased upon curcumin treatment.
      Our results not only revealed molecular mechanisms underlying curcumin action in
      uterine decidual cells but also suggest that this compound may have therapeutic
      potential for the prevention of inflammation-mediated preterm birth and other
      gestational disorders.

PMID- 25961580
TI  - Shikonin Suppresses Skin Carcinogenesis via Inhibiting Cell Proliferation.
AB  - The M2 isoform of pyruvate kinase M2 (PKM2) has been shown to be up-regulated in
      human skin cancers. To test whether PKM2 may be a target for chemoprevention,
      shikonin, a natural product from the root of Lithospermum erythrorhizon and a
      specific inhibitor of PKM2, was used in a chemically-induced mouse skin
      carcinogenesis study. The results revealed that shikonin treatment suppressed
      skin tumor formation. Morphological examinations and immunohistochemical staining
      of the skin epidermal tissues suggested that shikonin inhibited cell
      proliferation without inducing apoptosis. Although shikonin alone suppressed PKM2
      activity, it did not suppress tumor promoter-induced PKM2 activation in the skin
      epidermal tissues at the end of the skin carcinogenesis study. To reveal the
      potential chemopreventive mechanism of shikonin, an antibody microarray analysis
      was performed, and the results showed that the transcription factor ATF2 and its
      downstream target Cdk4 were up-regulated by chemical carcinogen treatment;
      whereas these up-regulations were suppressed by shikonin. In a promotable skin
      cell model, the nuclear levels of ATF2 were increased during tumor promotion,
      whereas this increase was inhibited by shikonin. Furthermore, knockdown of ATF2
      decreased the expression levels of Cdk4 and Fra-1 (a key subunit of the activator
      protein 1. In summary, these results suggest that shikonin, rather than
      inhibiting PKM2 in vivo, suppresses the ATF2 pathway in skin carcinogenesis. 

PMID- 25961582
TI  - Transfection of RNA from organ samples of infected animals represents a highly
      sensitive method for virus detection and recovery of classical swine fever virus.
AB  - Translation and replication of positive stranded RNA viruses are directly
      initiated in the cellular cytoplasm after uncoating of the viral genome.
      Accordingly, infectious virus can be generated by transfection of RNA genomes
      into susceptible cells. In the present study, efficiency of conventional virus
      isolation after inoculation of cells with infectious sample material was compared
      to virus recovery after transfection of total RNA derived from organ samples of
      pigs infected with Classical swine fever virus (CSFV). Compared to the
      conventional method of virus isolation applied in three different porcine cell
      lines used in routine diagnosis of CSF, RNA transfection showed a similar
      efficiency for virus rescue. For two samples, recovery of infectious virus was
      only possible by RNA transfection, but not by the classical approach of virus
      isolation. Therefore, RNA transfection represents a valuable alternative to
      conventional virus isolation in particular when virus isolation is not possible,
      sample material is not suitable for virus isolation or when infectious material
      is not available. To estimate the potential risk of RNA prepared from sample
      material for infection of pigs, five domestic pigs were oronasally inoculated
      with RNA that was tested positive for virus rescue after RNA transfection. This
      exposure did not result in viral infection or clinical disease of the animals. In
      consequence, shipment of CSFV RNA can be regarded as a safe alternative to
      transportation of infectious virus and thereby facilitates the exchange of virus
      isolates among authorized laboratories with appropriate containment facilities. 

PMID- 25961583
TI  - Synthesis of Hindered Biaryls via Aryne Addition and in Situ Dimerization.
AB  - Benzynes generated under Knochel conditions from 2-iodophenylsulfonates and
      (i)PrMgCl smoothly add to thiol, selenol, and amine nucleophiles. Treatment of
      the resulting aryl Grignard intermediate with a copper salt and an organic
      oxidant then affords symmetrical biaryls in good yield. 3-Substituted arynes
      undergo regioselective addition, enabling synthesis of atropisomeric biaryls with
      chelating S, Se, or N groups in the 2,2' positions. 

PMID- 25961581
TI  - Ano1/TMEM16A Overexpression Is Associated with Good Prognosis in PR-Positive or
      HER2-Negative Breast Cancer Patients following Tamoxifen Treatment.
AB  - The calcium-activated chloride channel Ano1 (TMEM16A) is overexpressed in many
      tumors. Although Ano1 overexpression is found in breast cancer due to 11q13
      amplification, it remains unclear whether signaling pathways are involved in Ano1
      overexpression during breast cancer tumorigenesis in vivo. Estrogen receptor
      (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2
      (HER2) have been known to contribute to breast cancer progression. It is unclear
      whether Ano1 is associated with clinical outcomes in breast cancer patients with
      different ER, PR and HER2 status. In the present study, we investigated the Ano1
      expression in 431 patients with invasive ductal breast carcinoma and 46 patients
      with fibroadenoma, using immunohistochemistry, and analyzed the association
      between Ano1 expression and clinical characteristics and outcomes of breast
      cancer patients with different ER, PR, and HER2 status. Ano1 was overexpressed in
      breast cancer compared with fibroadenoma. Ano1 was significantly more associated
      with breast cancer with the lower clinical stage (stage I or II), or triple
      negative status. Mostly importantly, Ano1 overexpression was associated with good
      prognosis in patients with the PR-positive or HER2-negative status, and in
      patients following tamoxifen treatment. Multivariate Cox regression analysis
      showed that Ano1 overexpression was a prognostic factor for longer overall
      survival in PR-positive or HER2-negative patients, and a predictive factor for
      longer overall survival in patients following tamoxifen treatment. Our findings
      suggest that Ano1 may be a potential marker for good prognosis in PR-positive or
      HER2-negative patients following tamoxifen treatment. The PR and HER2 status
      defines a subtype of breast cancer in which Ano1 overexpression is associated
      with good prognosis following tamoxifen treatment. 

PMID- 25961585
TI  - Advances in concussion research: an applied research area with significant
      implications for the future conduct of brain science. Introduction.

PMID- 25961584
TI  - Rescue of alphaB Crystallin (HSPB5) Mutants Associated Protein Aggregation by Co
      Expression of HSPB5 Partners.
AB  - HSPB5 (also called alphaB-crystallin) is a ubiquitously expressed small heat
      shock protein. Mutations in HSPB5 have been found to cause cataract, but are also
      associated with a subgroup of myofibrillar myopathies. Cells expressing each of
      these HSPB5 mutants are characterized by the appearance of protein aggregates of
      primarily the mutant HSPB5. Like several members of the HSPB family, HSPB5 can
      form both homo-oligomeric and hetero-oligomeric complexes. Previous studies
      showed that co-expression of HSPB1 and HSPB8 can prevent the aggregation
      associated with the HSPB5 (R120G) mutant in cardiomyocytes and in transgenic
      mice. In this study, we systematically compared the effect of co-expression of
      each of the members of the human HSPB family (HSPB1-10) on the aggregation of
      three different HSPB5 mutants (R120G, 450 Delta A, 464 Delta CT). Of all members,
      co-expression of HSPB1, HSPB4 and HSPB5 itself, most effectively prevent the
      aggregation of these 3 HSPB5 mutants. HSPB6 and HSPB8 were also active but less,
      whilst the other 5 HSPB members were ineffective. Co-expression of Hsp70 did not
      reduce the aggregation of the HSPB5 mutants, suggesting that aggregate formation
      is most likely not related to a toxic gain of function of the mutants per se, but
      rather related to a loss of chaperone function of the oligomeric complexes
      containing the HSPB5 mutants (dominant negative effects). Our data suggest that
      the rescue of aggregation associated with the HSPB5 mutants is due to competitive
      incorporation of its partners into hetero-oligomers hereby negating the dominant
      negative effects of the mutant on the functioning of the hetero-oligomer. 

PMID- 25961586
TI  - A call to arms: the need to create an inter-institutional concussion neuroimaging
      consortium to discover clinically relevant diagnostic biomarkers and develop
      evidence-based interventions to facilitate recovery.

PMID- 25961587
TI  - FMRI of visual working memory in high school football players.
AB  - Visual working memory deficits have been observed in at-risk athletes. This study
      uses a visual N-back working memory functional magnetic resonance imaging task to
      longitudinally assess asymptomatic football athletes for abnormal activity.
      Athletes were increasingly "flagged" as the season progressed. Flagging may
      provide early detection of injury. 

PMID- 25961588
TI  - Repeat baseline assessment in college-age athletes.
AB  - Repeat baseline testing scores from one collegiate Division I NCAA school were
      analyzed to determine the necessity of this practice. ImPACT tests were taken
      between 13 and 40 months apart (median 24 months; final N = 67). No significant
      difference in any test composite score was obtained; the number of tests
      exceeding chance levels of change was insignificant. The results do not support
      the recommendation for repeating baseline testing in college athletes;
      replication is recommended. 

PMID- 25961589
TI  - The role of location of subconcussive head impacts in FMRI brain activation
      change.
AB  - Monte-Carlo permutation analysis was used to identify sets of head impacts most
      predictive of functional magnetic resonance imaging (fMRI) changes in football
      players. The relative distribution of impact location was found to be more
      predictive of brain activation changes than the number of impacts, suggesting
      that fMRI changes are related to systematic playing style. 

PMID- 25961590
TI  - Cerebrovascular reactivity alterations in asymptomatic high school football
      players.
AB  - Cerebrovascular reactivity (CVR) is impaired following brain injury, increasing
      susceptibility to subsequent injury. CVR was tracked in football and non
      collision athletes throughout one season. CVR transiently decreased in football
      athletes during the first half of the season. Results indicate the brain adapts
      slowly to increases in loading, increasing risk for injury. 

PMID- 25961591
TI  - Post-Season Neurophysiological Deficits Assessed by ImPACT and fMRI in Athletes
      Competing in American Football.
AB  - Neurocognitive assessment, functional magnetic resonance imaging, and head impact
      monitoring were used to evaluate neurological changes in high school football
      players throughout competitive seasons. A substantial number of asymptomatic
      athletes exhibited neurophysiological changes that persisted post-season, with
      abnormal measures significantly more common in athletes receiving 50 or more hits
      per week during the season. 

PMID- 25961592
TI  - DTI Detection of Longitudinal WM Abnormalities Due to Accumulated Head Impacts.
AB  - Longitudinal evaluation using diffusion-weighted imaging and collision event
      monitoring was performed on high school athletes who participate in American
      football. Observed changes in white matter health were suggestive of injury and
      found to be correlated with accumulation of head collision events during
      practices and games. 

PMID- 25961595
TI  - Children With Obesity: How Are They Different?

PMID- 25961596
TI  - Ultrasound of the Whole Arm to Manage Suspected Upper-Extremity Deep Venous
      Thrombosis.

PMID- 25961594
TI  - MicroRNA networks regulated by all-trans retinoic acid and Lapatinib control the
      growth, survival and motility of breast cancer cells.
AB  - SKBR3-cells, characterized by ERBB2/RARA co-amplification, represent a subgroup
      of HER2+ breast-cancers sensitive to all-trans retinoic acid (ATRA) and
      Lapatinib. In this model, the two agents alone or in combination modulate the
      expression of 174 microRNAs (miRs). These miRs and predicted target-transcripts
      are organized in four interconnected modules (Module-1 to -4). Module-1 and
      Module-3 consist of ATRA/Lapatinib up-regulated and potentially anti-oncogenic
      miRs, while Module-2 contains ATRA/Lapatinib down-regulated and potentially pro
      oncogenic miRs. Consistent with this, the expression levels of Module-1/-3 and
      Module-2 miRs are higher and lower, respectively, in normal mammary tissues
      relative to ductal-carcinoma-in-situ, invasive-ductal-carcinoma and metastases.
      This indicates associations between tumor-progression and the expression profiles
      of Module-1 to -3 miRs. Similar associations are observed with tumor
      proliferation-scores, staging, size and overall-survival using TCGA (The Cancer
      Genome Atlas) data. Forced expression of Module-1 miRs, (miR-29a-3p; miR-874-3p)
      inhibit SKBR3-cell growth and Module-3 miRs (miR-575; miR-1225-5p) reduce growth
      and motility. Module-2 miRs (miR-125a; miR-193; miR-210) increase SKBR3 cell
      growth, survival and motility. Some of these effects are of general significance,
      being replicated in other breast cancer cell lines representing the heterogeneity
      of this disease. Finally, our study demonstrates that HIPK2-kinase and the PLCXD1
      phospholipase-C are novel targets of miR-193a-5p/miR-210-3p and miR-575/miR-1225
      5p, respectively. 

PMID- 25961597
TI  - A Microfluidic Platform for Evaluating Neutrophil Chemotaxis Induced by Sputum
      from COPD Patients.
AB  - Chronic Obstructive Pulmonary Disease (COPD) is a common lung disease
      characterized by breathing difficulty as a consequence of narrowed airways.
      Previous studies have shown that COPD is correlated with neutrophil infiltration
      into the airways through chemotactic migration. However, whether neutrophil
      chemotaxis can be used to characterize and diagnose COPD is not well established.
      In the present study, we developed a microfluidic platform for evaluating
      neutrophil chemotaxis to sputum samples from COPD patients. Our results show
      increased neutrophil chemotaxis to COPD sputum compared to control sputum from
      healthy individuals. The level of COPD sputum induced neutrophil chemotaxis was
      correlated with the patient's spirometry data. The cell morphology of neutrophils
      in a COPD sputum gradient is similar to the morphology displayed by neutrophils
      exposed to an IL-8 gradient, but not a fMLP gradient. In competing gradients of
      COPD sputum and fMLP, neutrophils chemotaxis and cell morphology are dominated by
      fMLP. 

PMID- 25961598
TI  - Lesbian, Gay, Bisexual, and Transgender Health Disparities: Executive Summary of
      a Policy Position Paper From the American College of Physicians.
AB  - In this position paper, the American College of Physicians examines the health
      disparities experienced by the lesbian, gay, bisexual, and transgender (LGBT)
      community and makes a series of recommendations to achieve equity for LGBT
      individuals in the health care system. These recommendations include enhancing
      physician understanding of how to provide culturally and clinically competent
      care for LGBT individuals, addressing environmental and social factors that can
      affect their mental and physical well-being, and supporting further research into
      understanding their unique health needs. 

PMID- 25961599
TI  - Methods in pediatric sleep research and sleep medicine.
AB  - Several methods are used to evaluate sleep in infants, children, and adolescents
      including: Questionnaires and diaries, actigraphy, polysomnography, and
      electroencephalography which are well established. Novel approaches such as high
      density electroencephalography, simultaneous electroencephalography-functional
      magnetic resonance imaging and nonpharmacological methods aiming for a modulation
      of sleep are currently only used for research. These approaches might become
      valuable methods for clinical application in the future. The purpose of this
      review is to present an overview of current methods and their respective fields
      of application and to report available rules and recommendations for their use. 

PMID- 25961600
TI  - Narcolepsy during Childhood: An Update.
AB  - Narcolepsy type 1 (NT1) is a rare central disorder of hypersomnolence
      characterized by excessive daytime sleepiness, cataplexy, sleep paralysis,
      hallucinations, and fragmented nocturnal sleep usually arising in adolescence or
      young adulthood. Recently, the childhood NT1 diagnoses have increased for
      improved disease awareness and for several cases occurring after the H1N1
      pandemic influenza or vaccination. As in adults, the occurrence of NT1 in
      individuals with a genetic predisposition of the immune system (e.g., human
      leukocyte antigen, HLA-DQB1*0602) together with the role of environmental
      triggers (e.g., H1N1 influenza virus, streptococcus beta hemolyticus) further
      supports the autoimmune pathogenesis. Children with NT1 close to disease onset
      show a peculiar cataplexy phenotype characterized by persistent hypotonia with
      prominent facial involvement (cataplectic facies) and by a complex mosaic of
      hyperkinetic movement abnormalities that increase during emotional stimulation.
      This phenotype progressively vanishes along the disease course leading to the
      typical picture of cataplexy (i.e., muscle weakness exclusively evoked by strong
      emotions). This possibly explains in part the misdiagnoses and diagnostic delay.
      Childhood NT1 also shows behavioral abnormalities and psychiatric disorders,
      encompassing depressive feelings, hyperactive/aggressive behavior, up to
      psychotic features. The association with obesity and precocious puberty
      strikingly suggests that NT1 arising in prepubertal children may reflect a wide
      hypothalamic derangement secondary to hypocretin neuronal loss. The complexity of
      the childhood NT1 phenotype claims a multidisciplinary assessment and management,
      taking behavioral and endocrinological features into account. NT1 indeed is a
      lifelong disorder with a devastating impact on quality of life, especially when
      arising across developmental age, and targeted school programs, medicolegal and
      psychological supports are essential for patients care. Controlled studies are
      mandatory to assess safety and efficacy of the current symptomatic off-label
      medications on which also relies the treatment for children with NT1, and
      hopefully future pathogenetic evidences will pave the way to better disease
      prevention and therapies to modify the disease course. 

PMID- 25961601
TI  - Relationships between Diet, Alcohol Preference, and Heart Disease and Type 2
      Diabetes among Americans.
AB  - Although excessive alcohol consumption is a recognized cause of morbidity and
      mortality, many studies have linked moderate alcohol consumption to improved
      cardiovascular health and a lower risk of Type 2 Diabetes (T2D). Self-reported
      alcohol and diet data used to generate these results suffer from measurement
      error due to recall bias. We estimate the effects of diet, alcohol, and lifestyle
      choices on the prevalence and incidence of cardiovascular disease and T2D among
      U.S. adults using a nationally representative cohort of households with scanner
      data representing their food-at-home, alcohol, and tobacco purchases from 2007
      2010, and self-reported health surveys for the same study participants from 2010
      2012. Multivariate regression models were used to identify significant
      associations among purchase data and lifestyle/demographic factors with disease
      prevalence in 2010, and with incidence of new disease from 2011-2012. After
      controlling for important confounders, respondents who purchased moderate levels
      of wine were 25% less likely than non-drinkers to report heart disease in 2010.
      However, no alcohol-related expenditure variables significantly affected the
      likelihood of reporting incident heart disease from 2011-2012. In contrast, many
      types of alcohol-related purchases were associated with a lower prevalence of
      T2D, and respondents who purchased the greatest volumes of wine or beer--but not
      liquor--were less likely to report being diagnosed with T2D in 2011-2012 than non
      drinkers.

PMID- 25961602
TI  - Treatment challenges for the young patient with type 1 diabetes.

PMID- 25961603
TI  - Glycemic variability: challenges in interpretation.

PMID- 25961604
TI  - Self-Control of Task Difficulty During Early Practice Promotes Motor Skill
      Learning.
AB  - This study was designed to determine whether the effect of self-control of task
      difficulty on motor learning is a function of the period of self-control
      administration. In a complex anticipation-coincidence task that required
      participants to intercept 3 targets with a virtual racquet, the task difficulty
      was either self-controlled or imposed to the participants in the two phases of
      the acquisition session. First, the results confirmed the beneficial effects of
      self-control over fully prescribed conditions. Second, the authors also
      demonstrated that a partial self-control of task difficulty better promotes
      learning than does a complete self-controlled procedure. Overall, the results
      revealed that these benefits are increased when this choice is allowed during
      early practice. The findings are discussed in terms of theoretical and applied
      perspectives. 

PMID- 25961605
TI  - Scientific misconduct.

PMID- 25961606
TI  - Influence of refractory on the color of VM7 metal free ceramics.
AB  - INTRODUCTION: The aim of this study was to evaluate the influence of metal oxides
      from investment dies on the color of metal-free VM7 ceramic. MATERIALS AND
      METHODS: Forty circular patterns were made with an elastic gelatin duplicator.
      These were divided into four groups (n = 10) for pouring the investment: G1,
      Begoform (Bego); G2, Ducera Lay Superfit (DeguDent GmbH); G3, Duravest
      (Polidental), and G4, Refrax Magnum (CNG). Refractory dies were subjected to the
      degassing process for gas and metal oxide elimination, and the testing was done
      with the application of two layers of VM7 ceramic. These layers were sinterized
      in accordance with the manufacturer's recommendation and then glazed. For the
      control group, 10 additional VM7 ceramic discs were made without the use of any
      investment die. The ceramic's control color and the tested groups were analyzed
      with the aid of a portable colorimeter (Minolta CR-10) in the CIELab. The color
      change (DeltaE) of the specimens from the tested groups was obtained, and the
      data were submitted to one-way ANOVA and post-hoc Tukey's test. RESULTS: All
      tested groups had a color change from the control group. G1 (5,3) and G2 (5,3)
      were those that showed the greater color change and did not show statistical
      differences between themselves; G3 (3,3) and G4 (3,1) were those that showed the
      least color change from control group and did not show statistical differences
      between themselves. CONCLUSION: Once all investments present a perceptible color
      change from the control group, color selection should be done with a laboratory
      produced color scale.

PMID- 25961607
TI  - Detection of proximal caries using digital radiographic systems with different
      resolutions.
AB  - BACKGROUND: Dental radiography is an important tool for detection of caries and
      digital radiography is the latest advancement in this regard. Spatial resolution
      is a characteristic of digital receptors used for describing the quality of
      images. AIM: This study was aimed to compare the diagnostic accuracy of two
      digital radiographic systems with three different resolutions for detection of
      noncavitated proximal caries. SETTINGS AND DESIGN: Diagnostic accuracy. MATERIALS
      AND METHODS: Seventy premolar teeth were mounted in 14 gypsum blocks. Digora;
      Optime and RVG Access were used for obtaining digital radiographs. Six observers
      evaluated the proximal surfaces in radiographs for each resolution in order to
      determine the depth of caries based on a 4-point scale. The teeth were then
      histologically sectioned, and the results of histologic analysis were considered
      as the gold standard. Data were entered using SPSS version 18 software and the
      Kruskal-Wallis test was used for data analysis. P <0.05 was considered as
      statistically significant. RESULTS: No significant difference was found between
      different resolutions for detection of proximal caries (P > 0.05). RVG access
      system had the highest specificity (87.7%) and Digora; Optime at high resolution
      had the lowest specificity (84.2%). Furthermore, Digora; Optime had higher
      sensitivity for detection of caries exceeding outer half of enamel. Judgment of
      oral radiologists for detection of the depth of caries had higher reliability
      than that of restorative dentistry specialists. CONCLUSION: The three resolutions
      of Digora; Optime and RVG access had similar accuracy in detection of
      noncavitated proximal caries.

PMID- 25961608
TI  - A study to evaluate the correlation of serum albumin levels with chronic
      periodontitis.
AB  - CONTEXT: Periodontitis is a chronic inflammatory disease caused by bacterial
      infection of the supporting tissues around the teeth. Serum albumin levels might
      be the practical marker of general health status. Albumin concentration is
      associated with nutrition and inflammation. AIMS: The aim of this study was to
      evaluate the relationship between periodontal health status and serum albumin
      levels. SUBJECTS AND METHODS: A total of 60 subjects of both genders with age
      range of 40-70 years were included in the study. Patients were divided into two
      groups viz. Group I; clinically healthy subjects and Group II; patients with
      chronic periodontitis, that is, loss of attachment >=5 mm. Serum albumin
      concentration was estimated by bromocresol green albumin method. STATISTICAL
      ANALYSIS USED: Student's unpaired t-test. RESULTS: The mean value of serum
      albumin levels for Group I was 4.815 g/dL with standard deviation (SD) of 0.127
      and for Group II, the mean value of serum albumin levels was 4.219 g/dL (SD
      0.174). The difference between serum albumin levels in Group I and Group II were
      found to be statistically significant ( P <= 0.001). CONCLUSIONS: The findings of
      this clinical trial suggest an inverse relationship between the serum albumin
      concentration and chronic periodontal disease.

PMID- 25961609
TI  - Marginal and internal discrepancies of zirconia copings: effects of milling
      system and finish line design.
AB  - CONTEXT: Discrepancies at the abutment/crown interface can affect the longevity
      of zirconia restorations. AIM: The aim was to evaluate the marginal and internal
      discrepancies (MD and ID) of zirconia copings manufactured by two milling systems
      with different finish lines. MATERIALS AND METHODS: Three aluminum-master-dies (h
      = 5.5 mm; Psi =7.5 mm; 6?), with different finish lines (large chamfer [LC];
      tilted chamfer [TC]; rounded shoulder [RS]) were fabricated. Twenty impressions
      were made from each master die and poured. Sixty zirconia copings were
      manufactured and divided according to the factors "finish line" and "milling
      system" (n = 10): CAD LC = Computer-aided design/computer-aided manufacturing
      (CAD/CAM) + LC; CAD TC = CAD/CAM + TC; CAD RS = CAD/CAM + RS; MAD LC = manually
      aided design/manually aided manufacturing (MAD/MAM) + LC; MAD TC = MAD/MAM + TC;
      and MAD RS = MAD/MAM + RS. For MD analysis, each coping was fixed, and the
      distance between the external edges of the coping and the edge of the cervical
      preparation was measured (50 points). Using the same copings, the ID of each
      coping was evaluated, by the replica technique, at 12 points equally distributed
      among the regions (n = 10): Ray (R), axial (A), and occlusal (Occl). The
      measurements were performed by optical microscopy (Chi250). The data (MUm) were
      subjected to parametric and non-parametric statistical analyses. RESULTS: For the
      MAD/MAM system, the "finish line" (P = 0.0001) affected significantly the MD
      median values (MUm): LC = 251.80 a , RS = 68.40 a and TC = 8.10 b (Dunn's test).
      For the CAD/CAM system, the median MD values (MUm) were not affected by the
      factor "finish line" (P = 0.4037): LC = 0.82 a , RS = 0.52 a , and TC = 0.89 a .
      For the ID, it was observed interaction between the finish line types and the
      region (P = 0.0001) and between region and milling system (P = 0.0031) (RM
      ANOVA). CONCLUSIONS: The CAD/CAM system presented lower MD values, regardless the
      finish line. However, the MAD/MAM system showed ID values smaller than those of
      CAD/CAM.

PMID- 25961610
TI  - Awareness of the association between periodontal disease and adverse pregnancy
      outcome among the general female population.
AB  - BACKGROUND: Preterm low birth weight (PTLBW) is a public health issue which needs
      to be dealt with by educating the general female population. One of the major
      contributing factors is periodontal disease and treatment of the same could
      reduce the occurrence of PTLBW babies. Therefore, awareness of this among the
      female population is highly essential. Hence, this survey was planned with the
      aim to explore the awareness of the general female population regarding the
      association of periodontal disease and PTLBW. MATERIAL AND METHODS: This survey
      consisted of nine close-ended questions answered by 1284 females. RESULTS:
      Younger individuals had higher knowledge scores as compared to the older
      individuals (r = -0.161) and the more educated group had a higher knowledge score
      as compared to the less educated groups (r = 0.322). Furthermore, married women
      seemed to be more aware of the relation of PTLBW to periodontal disease as
      compared to unmarried women. CONCLUSION: Younger and educated females had better
      awareness of the association between periodontal diseases and PTLBW. Hence,
      efforts to educate the general female population on this association could
      contribute toward the reduction of the risk of PTLBW.

PMID- 25961611
TI  - Grading angiogenesis in oral squamous cell carcinoma: a histomorphometric study.
AB  - CONTEXT: Like normal tissues, tumors require an adequate supply of oxygen,
      metabolites and an effective way to remove waste products. This is achieved by
      angiogenesis, which is defined as the process by which new blood vessels are
      produced by sprouting from preexisting vasculature. There is a large spectrum of
      physiological and pathological processes in which angiogenesis occur, ranging
      from tissue hypertrophy, wound healing, and inflammation to tumors. AIMS: The
      present study was designed to morphometrically evaluate the angiogenesis in
      different grades of oral squamous cell carcinomas (OSCCs) under light microscope
      by the use of H and E stained sections and to assess that whether the parameters
      of vascularity like mean vascular density (MVD), mean vascular area (MVA), and
      total vascular area (TVA) can be used to histologically grade the tumors.
      SUBJECTS AND METHODS: A total of 10 cases each of well-, moderately- and poorly
      differentiated SCC cases were retrieved from the archives of the Department of
      Oral Pathology and Microbiology and were morphometrically analyzed for mean
      vascular density (MVD), MVA, and TVA. Ten cases of normal oral mucosa were taken
      as Control. Statistical analysis was done using  SPSS 19.0 version (IBM, Armonk,
      NY, USA) software for windows. Group mean for MVD, TVA and MVA were calculated
      for 10 cases of each group. "Student's t-test" was applied to assess the
      intergroup variation of mean values of MVD, TVA, and MVA. RESULTS: Our results
      showed significant differences between all the three parameters, that is, MVD,
      MVA and TVA when poorly differentiated OSCC was compared with the normal mucosa,
      well- and moderately-differentiated OSCC. However, when comparison was made
      between the well- and moderately-differentiated OSCC, the differences in the
      three parameters were present but not statistically significant. CONCLUSION:
      There was an increased MVD, MVA and TVA in poorly differentiated OSCC, which
      could be used as an additional criterion to histologically grade the tumor.

PMID- 25961612
TI  - Multidetector computed tomography dentascan analysis of root canal morphology of
      maxillary canine.
AB  - AIM: The aims of this in vitro study were to see potential applications of
      multidetector computed tomography (MDCT) in the analysis of root canal
      morphology. MATERIALS AND METHODS: In this in vitro study measurement of root and
      canal diameters, root and canal diameter ratios, and radicular wall thickness at
      different levels in maxillary canines with long oval root canals. A total of 40
      human maxillary canines, with single long oval canals were selected for this
      study. The specimens were analyzed with MDCT (16 slice) through dentascan
      software. The cross-sections corresponding to 625 mm slice thickness from the
      radiologic apex were analyzed to measure the mesiodistal (MD) and buccolingual
      (BL) diameters of the canals and the thickness of the root and the walls. The
      BL/MD ratios of the canal (?C) and the root (?R) diameters were calculated, as
      was as the mean taper in both a BL and an MD dimension. RESULTS: A high
      correlation was established between the shape of the root canal and the
      corresponding root. CONCLUSION: Clinical Implications of these techniques is
      useful to clinician and it can also be applied to improve preclinical training
      and analysis of fundamental procedures in endodontic and restorative treatment.

PMID- 25961613
TI  - Evaluation of three different agents for in-office treatment of dentinal
      hypersensitivity: a controlled clinical study.
AB  - CONTEXT: Dentin desensitizers are used for in-office treatment of dentinal
      hypersensitivity. They block the open tubules and bring about a reduction in
      hypersensitivity. AIM: The aim was to evaluate and compare the clinical
      effectiveness of a dentin desensitizer, a combination of a dentin desensitizer +
      adhesive and one-bottle self-etching adhesive for in-office treatment of dentin
      hypersensitivity. SETTINGS AND DESIGN: Institutional, prospective double-blind
      parallel clinical design. SUBJECTS AND METHODS: A total of 54 teeth in 20
      patients were randomly allocated to one of the three study groups, with 18 teeth
      in each group as follows: Group A-Gluma Desensitizer (GD), Group B-Gluma Comfort
      Bond + Desensitizer (GCBD), Group C-Single Bond Universal (SBU). The patients'
      dentinal hypersensitivity scores for tactile (hand-held scratch device), thermal
      (cold), and evaporative (dental unit air syringe) stimuli were recorded on a
      visual analog scale. The parameters were recorded at baseline, immediately after
      application of the agent, 3- and 6-week posttreatment. STATISTICAL ANALYSIS USED:
      The data were analyzed with Friedman's test, Wilcoxon signed ranks test, Kruskal
      Wallis test, and Mann-Whitney-U-test (P < 0.05). RESULTS: All three groups showed
      a significant reduction in dentinal hypersensitivity (P < 0.05) compared to
      baseline at all time intervals. Statistically, significant differences were noted
      between GD and SBU; between GCBD and SBU in all testing parameters. Between GD
      and GCBD no significant difference was noted. CONCLUSIONS: GD and GCBD showed a
      greater reduction in dentin hypersensitivity than SBU.

PMID- 25961614
TI  - C-reactive protein estimation: a quantitative analysis for three nonsteroidal
      anti-inflammatory drugs: a randomized control trial.
AB  - CONTEXT: C-reactive protein (CRP) estimation for quantitative analysis to assess
      anti-inflammatory action of nonsteroidal anti-inflammatory drugs (NSAIDs) after
      surgery in maxillofacial surgery. AIMS: This study was to evaluate the efficacy
      of CRP as a quantitative analysis for objective assessment of efficacy of three
      NSAIDs in postoperative inflammation and pain control. SETTINGS AND DESIGN: The
      parallel study group design of randomization was done. Totally 60 patients were
      divided into three groups. CRP was evaluated at baseline and postoperatively
      (immediate and 72 h) after surgical removal of impacted lower third molar. The
      respective group received the drugs by random coding postoperatively. SUBJECTS
      AND METHODS: The assessment of pain control and inflammation using NSAIDs
      postoperatively after surgical removal of impacted lower third molar was
      qualitatively and quantitatively assessed with CRP levels. The blood sample of
      the patient was assessed immediate postoperatively and after 72 h. The visual
      analog scale (VAS) was used for assessment of pain and its correlation with CRP
      levels. STATISTICAL ANALYSIS: Comparison of difference in levels of CRP levels
      had P < 0.05 with immediate postoperative and baseline levels. The duration of
      surgery with association of CRP levels P = 0.425 which was nonsignificant. The
      pain score was increased with mefenamic acid (P = 0.003), which was significant
      on VAS. RESULTS: Diclofenac had the best anti-inflammatory action. There was a
      significant increase in CRP levels in immediate postoperative values and 72 h.
      CRP test proved to be a useful indicator as a quantitative assessment tool for
      monitoring postsurgical inflammation and therapeutic effects of various anti
      inflammatory drugs. CONCLUSIONS: CRP test is a useful indicator for quantitative
      assessment for comparative evaluation of NSAIDs.

PMID- 25961615
TI  - Prevalence of dental caries, periodontitis, and oral hygiene status among 12-year
      old schoolchildren having normal occlusion and malocclusion in Mathura city: a
      comparative epidemiological study.
AB  - OBJECTIVE: The aim was to find the prevalence of dental caries, periodontitis,
      and oral hygiene index-simplified (OHI-S) among 12-year schoolchildren having
      normal occlusion and malocclusion in Mathura city. MATERIALS AND METHODS: The
      present study was a cross-sectional study done among the 100 subjects who have
      been selected from 5 schools in four different geographical locations. The data
      regarding their socio-demographic characteristics, dental caries status,
      periodontitis status and oral hygiene status was collected using structured
      proforma. Means, standard deviations and test of significant were used as
      statistics to describe the data. RESULTS: The results showed that there was no
      significant difference between dental caries status, periodontitis status among
      subjects having normal occlusion and malocclusion (P = 0.06, 0.093) but
      significant relationship was found OHI-S and children who were having
      malocclusion (and P = 0.022). Significant difference was also found between
      periodontitis and oral hygiene status (P = 0.00). CONCLUSION: It was observed
      from the present study that normal occlusion and malocclusion had no or weak
      significant effect on overall caries and periodontitis prevalence whereas oral
      hygiene status had a strong effect on overall periodontitis prevalence but not in
      relation to prevalence of dental caries in 12-year-old school children in Mathura
      city.

PMID- 25961616
TI  - Comparative evaluation of natural curcumin and synthetic chlorhexidine in the
      management of chronic periodontitis as a local drug delivery: a clinical and
      microbiological study.
AB  - BACKGROUND OF THE STUDY: The aim of this study is to evaluate the efficacy of
      natural curcumin in the management of chronic periodontitis as local drug
      delivery in comparison to synthetic chlorhexidine, which is the gold standard.
      MATERIALS AND METHODS: Thirty chronic periodontitis patients with an age range of
      20-50 years with probing pocket depth (PPD) of 4-6 mm were included. Curcumin and
      chlorhexidine gel was applied in the contralateral disease sites at baseline and
      day 15. The clinical parameters like PPD, clinical attachment level (CAL),
      gingival index (Loe and Silness) and plaque index (Turesky Gillmore modification
      of Quigley Hein) were recorded and colony forming units (CFU) were assessed
      microbiologically at baseline, 15 and 30 days. RESULTS: There was a significant
      reduction of the clinical parameters (PPD, CAL) and microbiological parameters
      CFU at 15 and 30 days for both the groups. Curcumin group showed a greater
      reduction in the clinical parameters when compared with chlorhexidine group. Both
      groups had a significant reduction in parameters when compared with baseline.
      CONCLUSION: Although curcumin has equivalent benefit to chlorhexidine, curcumin
      being an ayurvedic herb is an excellent alternative to chlorhexidine due to
      minimal side-effects.

PMID- 25961617
TI  - Comparison of amine fluoride and chlorhexidine mouth rinses in the control of
      plaque and gingivitis--a randomized controlled clinical trial.
AB  - OBJECTIVES: The objective of this triple blind randomized controlled clinical
      trial was to compare the efficacy of a mouth rinse containing amine fluoride
      (AmF) and chlorhexidine in controlling the supragingival plaque accumulation and
      gingival inflammation during a 4-week period in patients with chronic gingivitis.
      SUBJECTS AND METHODS: A total of 30 patients were participated in this study.
      Fifteen patients were prescribed an AmF-containing mouth rinse and 15 were
      prescribed a chlorhexidine mouth rinse. Plaque index, gingival index, bleeding
      index, tooth stain, and tongue stain (TS) were recorded at baseline, 15 days and
      1-month. Patients' perception of odor, taste and any discomfort were recorded.
      RESULTS: The comparisons between the groups were done using Mann-Whitney U-test.
      The comparison within the group at different time visits were done using Wilcoxon
      signed rank test. Both the mouth rinses resulted in a significant decrease in
      plaque index, gingival index, bleeding index. However, AmF mouth rinse resulted
      in a statistically significant decrease in bleeding index and gingival index
      compared to chlorhexidine group. There was no significant difference in tooth
      stain and TS in both the groups. CONCLUSIONS: The 4 weeks use of AmF containing
      mouth rinse is effective in reducing the gingival inflammation and plaque.

PMID- 25961618
TI  - Demystifying the mesiobuccal root of maxillary first molar using cone-beam
      computed tomography.
AB  - CONTEXT: Imaging techniques and endodontics are inseparable from each other as
      the former have always been the cornerstone for successful endodontic diagnosis
      and treatment. AIMS: The objective of this study was to detect the presence of
      extra canals in the mesiobuccal root of the maxillary first molar using cone-beam
      computed tomography (CBCT). MATERIALS AND METHODS: In this study, 75 freshly
      extracted human maxillary first molars were mounted on arches and exposed to CBCT
      and digital radiography (control). The incidence of additional canals is then
      evaluated using CBCT and the teeth identified with additional canals were marked
      and again exposed to RVG. STATISTICAL ANALYSIS USED: The results were analyzed by
      three examiners two endodontists and an oral radiologist to eliminate bias. Inter
      and intra rater agreement was analyzed using the kappa coefficient. RESULTS:
      Statistical analysis revealed the incidence of extra canals to be at 47.1% with
      the difference between the readings of the 3 examiners being statistically
      insignificant. CONCLUSIONS: CBCT can be considered an advanced diagnostic tool
      for primary and secondary endodontic treatments.

PMID- 25961619
TI  - Apical extrusion of Enterococcus faecalis using three different rotary
      instrumentation techniques: an in vitro study.
AB  - AIMS: To compare the apical extrusion of Enterococcus faecalis after
      instrumentation with three different Ni-Ti rotary instruments- An in vitro study.
      SETTINGS AND DESIGN: In vitro study Methods and Material: Forty freshly extracted
      mandibular premolars were mounted in bacteria collection apparatus and root
      canals were contaminated with a suspension of Enterococcus faecalis. The
      contaminated teeth were divided into 4 groups of 10 teeth each according to
      rotary system used for instrumentation: Group1: Hyflex files, Group 2: GTX files,
      Group 3: Protaper files and Group 4: control group (no instrumentation). Bacteria
      extruded after preparations were collected into vials and microbiological samples
      were incubated in BHI broth for 24 hrs. The colony forming units were determined
      for each sample. STATISTICAL ANALYSIS USED: Statistical analysis was done using
      one way ANOVA followed by post hoc independent " t" test. RESULTS: GTX files
      extruded least amount of bacteria followed by Hyflex files. Maximum extrusion of
      E. faecalis was seen in rotary Protaper group. CONCLUSION: Least amount of
      extrusion was seen with GTX files followed by Hyflex files and then rotary
      Protaper system.

PMID- 25961620
TI  - Influence of polyurethane resin dies on the fit and adaptation of full veneer
      crowns.
AB  - CONTEXT: Polyurethane resin is a possible alternative to type IV dental stone for
      fabrication of indirect restorations however its dimensional accuracy is
      questionable. AIM: The aim was to investigate the dimensional accuracy of silica
      filled polyurethane resin die material by evaluating the marginal fit and
      adaptation of indirect gold castings. SETTINGS AND DESIGN: Experimental, in vitro
      study. MATERIALS AND METHODS: Totally 40 copper plated replicas of a nickel
      chrome master die analogous to a veneer gold crown preparation were made and
      impressions recorded using polyvinylsiloxane material. Twenty impressions were
      poured in type IV dental stone (control group (Vel-mix, Kerr, UK) and the
      remaining (n = 20) in silica filled polyurethane die material (test group) (Alpha
      Die MF, CA, USA). Gold castings were fabricated for each die using standardized
      techniques. The castings were seated on their respective copper plated dies,
      embedded in resin and sectioned. The specimens were analyzed by measuring
      marginal opening and the area beneath the casting at a *63 magnification and
      using image analysis software. STATISTICAL ANALYSIS USED: Data were analyzed
      using a Student's t-test. RESULTS: No significant difference was observed between
      the experimental groups (P > 0.05). The mean marginal opening for type IV, dental
      stone and polyurethane resin, was 57 +/- 22.6 MUm and 63.47 +/- 27.1 MUm,
      respectively. Stone displayed a smaller area beneath the casting (31581 +/- 16297
      MUm 2 ) as compared to polyurethane resin (35003 +/- 23039 MUm 2 ). CONCLUSIONS:
      The fit and adaptation of indirect gold castings made on polyurethane and type IV
      dental stone dies were comparable.

PMID- 25961621
TI  - Scanning electron microscopy analysis of microstructure of the adhesive interface
      between resin and dentin treated with papain gel.
AB  - AIM: The aim of this in vitro study was to observe and compare the microstructure
      of the adhesive interface between resin and dentin treated with Papacarie(r)
      using scanning electron microscopy (SEM). MATERIALS AND METHODS: Totally, 10
      human dentin slabs were randomly distributed into two groups. The control group
      (n = 5) was subjected to etching with 37% phosphoric acid for 20 s and washed for
      30 s, dried with absorbent paper, and the bonding agent was applied along with
      low viscosity resin. In turn, the experimental group (n = 5) was subjected to the
      same procedure, but Papacarie(r) (Fsigmarmula and Aetagammao, Sgammao Paulo,
      Brazil) was added for 30 s prior to etching. AdperTM Single Bond 2 (3M ESPE,
      Sgammao Paulo, Brazil) adhesive was applied to both groups following manufacturer
      instructions. The specimens were prepared for observation under SEM with *1.000,
      *2.000, *2.200 and *5.000 magnification. The micrographs were evaluated with
      respect to the formation of the hybrid layer, thickness, shape and length of the
      tags and microtags. RESULTS: In the experimental group there was the formation of
      more fine hybrid layer and tags with average of similar length to the control
      group; microtags in less number and without formation of lateral branches. The
      resin tags presented conical, smooth and uniform characteristics. CONCLUSIONS:
      When Papacarie(r) was used prior to the application of a bonding agent it could
      interfere with the formation of the hybrid layer without changing the length of
      the tag. Moreover, the morphology in the experimental group was found to be more
      uniform and regular.

PMID- 25961622
TI  - Maxillary first molar with seven root canals diagnosed with cone-beam computed
      tomography scanning.
AB  - Nonsurgical endodontic therapy of a right maxillary first molar with three roots
      and seven root canals. This unusual morphology was diagnosed using a dental
      operating microscope (DOM) and confirmed with the help of cone-beam computed
      tomography (CBCT) images. CBCT axial images showed that both the palatal and
      distobuccal root have a Vertucci type II canal pattern, whereas the mesiobuccal
      root showed a Sert and Bayirli type XVIII canal configuration. The use of a DOM
      and CBCT imaging in endodontically challenging cases can facilitate a better
      understanding of the complex root canal anatomy, which ultimately enables the
      clinician to explore the root canal system and clean, shape, and obturate it more
      efficiently.

PMID- 25961623
TI  - Therapeutic efficacy of a hybrid mandibular advancement device in the management
      of obstructive sleep apnea assessed with acoustic reflection technique.
AB  - Obstructive sleep apnea (OSA) is one of the most common forms of sleep-disordered
      breathing. Various treatment modalities include behavior modification therapy,
      nasal continuous positive airway pressure (CPAP), oral appliance therapy, and
      various surgical modalities. Oral appliances are noninvasive and recommended
      treatment modality for snoring, mild to moderate OSA cases and severe OSA cases
      when patient is not compliant to CPAP therapy and unwilling for surgery. Acoustic
      reflection technique (ART) is a relatively new modality for three-dimensional
      assessment of airway caliber in various clinical situations. The accuracy and
      reproducibility of acoustic rhinometry and acoustic pharyngometry assessment are
      comparable to computerized tomography and magnetic resonance imaging. This case
      report highlights the therapeutic efficacy of an innovative customized acrylic
      hybrid mandibular advancement device in the management of polysomnography
      diagnosed OSA cases, and the treatment results were assessed by ART.

PMID- 25961624
TI  - Analysis of the rate of maturogenesis of a traumatized Cvek's stage 3 anterior
      tooth treated with platelet-rich fibrin as a regenerative tool using three
      dimensional cone-beam computed tomography: an original case report.
AB  - Regenerative endodontic procedures are biologically based procedures which deal
      with the regeneration of pulp-like tissue, more idealistically the pulp-dentin
      complex. The regeneration of this pulp-dentin complex in an infected necrotic
      tooth with an open apex is possible only when the canal is effectively
      disinfected. Though there are various procedures for treating open apex ranging
      from Ca(OH) 2 apexification, mineral trioxide aggregate apexification and
      surgical approach, regeneration of tissues has always taken superior hand over
      the repair of tissues. The mechanics behind the regenerative endodontic
      procedures is that despite the tooth being necrotic, some pulp tissue can survive
      apically which under favorable conditions proliferate to aid in the process of
      regeneration. In the past 2 decades, an increased understanding of the
      physiological roles of platelets in wound healing and after tissue injury has led
      to the idea of using platelets as therapeutic tools in the field regenerative
      endodontics. In the present case report with an open apex, high sterilization
      protocol is followed using triple antibiotic paste as intra-canal medicament,
      followed which platelet rich fibrin is used as the regenerative material of
      choice. Over an 18-month follow-up period, clinically patient is asymptomatic and
      radiographically there is complete regression of the periapical lesion and
      initiation of the root end closure.

PMID- 25961625
TI  - Nonsurgical management of vascular malformation of masseter.
AB  - Intramuscular vascular anomalies are rare congenital hamartomatous lesions. Less
      than 1% of these occur in skeletal muscle out of which 15% arise in head and neck
      musculature. In the head and neck region, masseter muscle is the most common
      site. It accounts for about 5% of intramuscular vascular malformations. They are
      present from birth but are clinically apparent during infancy and childhood and
      occasionally during adulthood. Due to its location it is often mistaken for a
      parotid swelling. The usual treatment of choice is surgical excision with a
      margin. This is associated with loss of motor function, hemorrhage, nerve damage.
      Intralesional sclerotherapy, embolization are nonsurgical alternatives for
      treatment of slow flow venous malformations. Sclerotherapy can be used solely in
      multiple sittings or as an adjunct to surgery. This article presents a case
      report of a 28-year-old male with recurrent intramuscular vascular malformation
      in the masseter muscle, which was successfully treated by ethanol sclerotherapy.

PMID- 25961626
TI  - Extra-vascular type of oral intravascular papillary endothelial hyperplasia
      (Masson's tumor) of lower lip: a case report and review of the literature.
AB  - Intravascular papillary endothelial hyperplasia (IPEH) is an unusual reactive
      lesion of vascular origin, which rarely occurs in the oral cavity.
      Pathogenetically, is it divided into true, mixed and extra-vascular types. We
      report a case of extra-vascular IPEH of the lower lip in 54-year-old female
      patient. Patient gives history of trauma 4 months back with lesion developing at
      the site to trauma. The lesion was 3 cm * 4 cm in size with soft to firm in
      consistency. Histologically, it is characterized by an exuberant papillary
      endothelial cell proliferation toward the lumen of an enlarged blood vessel from
      the area of an organizing thrombus. The lesion was surgically excised under local
      anesthesia. The patient was followed for 1-year with no evidence of recurrence.
      This paper discusses the various aspects of IPEH of the oral cavity such as
      pathogenesis, clinical features, histopathology treatment, and prognosis. 

PMID- 25961627
TI  - Emerging technology and techniques.
AB  - A technique of fabricating feldspathic porcelain pressable ingots was proposed. A
      5 ml disposable syringe was used to condense the powder slurry. The condensed
      porcelain was sintered at 900?C to produce porcelain ingots. The fabricated
      porcelain ingots were used in pressable ceramic machines. The technological
      advantages of pressable system improve the properties, and the fabricated ingot
      enhances the application of feldspathic porcelain.

PMID- 25961628
TI  - Desensitizing paste use in children: boon or bane.

PMID- 25961629
TI  - Issues to be addressed for a randomized controlled trial.

PMID- 25961630
TI  - Pulmonary Hypertension: A Nomogram Based on CT Pulmonary Angiographic Data for
      Prediction in Patients without Pulmonary Embolism.
AB  - PURPOSE: To use cardiovascular data from computerized tomographic (CT) pulmonary
      angiography for facilitating the identification of pulmonary hypertension (PH) in
      patients without acute pulmonary embolism. MATERIALS AND METHODS: The
      institutional human research committee approved this retrospective study;
      informed consent was waived. Patients without pulmonary embolism who underwent CT
      pulmonary angiography and echocardiography within 24 hours of each other between
      December 2008 and October 2012 were retrospectively identified. The diameters of
      the pulmonary artery, aorta, and right and left ventricles and the severity of
      reflux of contrast material were assessed. The volumes of each cardiac
      compartment were calculated. Doppler echocardiography served as a reference
      standard for PH. A prediction model for PH was built by using backward logistic
      regression and was presented on a nomogram. The prediction model was evaluated
      with 10-fold cross-validation, and a test group of patients was studied between
      November 2012 and June 2014. RESULTS: The final study group included 182
      patients, of whom 98 (54%) were given a diagnosis of PH on the basis
      echocardiographic results. Age of 67 years or older (odds ratio [OR] = 4.46),
      reflux grade of 3 or higher (OR = 2.63), right atrial volume of greater than or
      equal to 106 cm(3) (OR = 3.59), pulmonary artery diameter greater than or equal
      to 28 mm (OR = 2.52) and pulmonary artery diameter to aorta diameter ratio of
      greater than or equal to 0.86 (OR = 2.17) were independently associated with PH.
      The logistic model showed good discrimination ability (area under the curve =
      0.844, discrimination slope = 0.359). Tenfold cross-validation showed 85.7%
      sensitivity, 60.7% specificity, 71.3% positive predictive value, and 76.1%
      negative predictive value for identification of PH, while the test group showed
      similar results (84.1%, 60.5%, 71.2%, and 76.7%, respectively). CONCLUSION:
      Cardiovascular data derived from CT pulmonary angiography are associated with PH,
      and a nomogram can be created that may facilitate identification of PH after
      exclusion of acute pulmonary embolism.

PMID- 25961631
TI  - Imaging Features and Prognosis of Hepatocellular Carcinoma in Patients with
      Cirrhosis Who Are Coinfected with Human Immunodeficiency Virus and Hepatitis C
      Virus.
AB  - PURPOSE: To evaluate the effect of human immunodeficiency virus (HIV) coinfection
      on hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-infected patients
      with cirrhosis in terms of HCC morphologic subtypes and survival prognosis at the
      time of radiologic diagnosis. MATERIALS AND METHODS: The study was approved by
      the institutional review board and patients gave their written informed consent.
      Two databases, one for HIV-HCV patients and the other for HCV-infected patients
      without HIV infection, were obtained from prospective multicenter cohorts.
      Inclusion criteria were a confirmed diagnosis of cirrhosis and the discovery of
      HCC at imaging between January 2008 and December 2012. This study included 35 HIV
      HCV patients with cirrhosis (32 men and three women; median age, 50 years [age
      range, 40-65 years]; Child-Pugh classification A, 21 patients; classification B,
      10 patients; classification C, four patients) and 35 infected HCV patients with
      cirrhosis (29 men and six women; median age, 56 years [age range, 41-83 years];
      Child-Pugh classification A, 26 patients; classification B, six patients;
      classification C, three patients) who were the control group. Computed
      tomographic or magnetic resonance images were analyzed for HCC subtypes, the
      number and size of nodules, and evidence of portal obstructing tumors. Fisher
      exact and Wilcoxon tests were used for comparisons and Kaplan-Meier plots were
      used for survival analysis. RESULTS: Infiltrative HCC was found in eight HIV-HCV
      patients with cirrhosis (23%) and in no HCV patients with cirrhosis (P = .002).
      All other HCCs were of a nodular type, with similar nodule sizes in the two
      groups. Portal-obstructing tumors were found in 10 HIV-HCV patients (eight of
      eight tumors were infiltrative and two of 27 tumors were nodular) but none were
      found in HCV patients (P = .001). Survival was dramatically shorter for HIV-HCV
      patients than for those with HCV, with a median of 17.2 months versus 54.7 months
      (P = .004). Survival time was dependent on the type of HCC, with probabilities of
      death at 12 months of 87% in infiltrative-type HCC, 32% in multiple-nodule type,
      and 5% in single-nodule type, which was found in both groups (log-rank test, P <
      .001). CONCLUSION: Unlike HCV-infected patients with cirrhosis, patients with
      cirrhosis coinfected with HIV and HCV frequently present at radiologic diagnosis
      with infiltrative-type HCC and portal-obstructing tumors, which results in
      dramatically shorter survival.

PMID- 25961633
TI  - Breast Cancer: Computer-aided Detection with Digital Breast Tomosynthesis.
AB  - PURPOSE: To evaluate a commercial tomosynthesis computer-aided detection (CAD)
      system in an independent, multicenter dataset. MATERIALS AND METHODS: Diagnostic
      and screening tomosynthesis mammographic examinations (n = 175; cranial caudal
      and mediolateral oblique) were randomly selected from a previous institutional
      review board-approved trial. All subjects gave informed consent. Examinations
      were performed in three centers and included 123 patients, with 132 biopsy-proven
      screening-detected cancers, and 52 examinations with negative results at 1-year
      follow-up. One hundred eleven lesions were masses and/or microcalcifications (72
      masses, 22 microcalcifications, 17 masses with microcalcifications) and 21 were
      architectural distortions. Lesions were annotated by radiologists who were aware
      of all available reports. CAD performance was assessed as per-lesion sensitivity
      and false-positive results per volume in patients with negative results. RESULTS:
      Use of the CAD system showed per-lesion sensitivity of 89% (99 of 111; 95%
      confidence interval: 81%, 94%), with 2.7 +/- 1.8 false-positive rate per view, 62
      of 72 lesions detected were masses, 20 of 22 were microcalcification clusters,
      and 17 of 17 were masses with microcalcifications. Overall, 37 of 39
      microcalcification clusters (95% sensitivity, 95% confidence interval: 81%, 99%)
      and 79 of 89 masses (89% sensitivity, 95% confidence interval: 80%, 94%) were
      detected with the CAD system. On average, 0.5 false-positive rate per view were
      microcalcification clusters, 2.1 were masses, and 0.1 were masses and
      microcalcifications. CONCLUSION: A digital breast tomosynthesis CAD system can
      allow detection of a large percentage (89%, 99 of 111) of breast cancers
      manifesting as masses and microcalcification clusters, with an acceptable false
      positive rate (2.7 per breast view). Further studies with larger datasets
      acquired with equipment from multiple vendors are needed to replicate the
      findings and to study the interaction of radiologists and CAD systems.

PMID- 25961634
TI  - Development and Validation of Electronic Health Record-based Triggers to Detect
      Delays in Follow-up of Abnormal Lung Imaging Findings.
AB  - Purpose To develop an electronic health record (EHR)-based trigger algorithm to
      identify delays in follow-up of patients with imaging results that are suggestive
      of lung cancer and to validate this trigger on retrospective data. Materials and
      Methods The local institutional review board approved the study. A "trigger"
      algorithm was developed to automate the detection of delays in diagnostic
      evaluation of chest computed tomographic (CT) images and conventional radiographs
      that were electronically flagged by reviewing radiologists as being "suspicious
      for malignancy." The trigger algorithm was developed through literature review
      and expert input. It included patients who were alive and 40-70 years old, and it
      excluded instances in which appropriate timely follow-up (defined as occurring
      within 30 days) was detected (eg, pulmonary visit) or when follow-up was
      unnecessary (eg, in patients with a terminal illness). The algorithm was
      iteratively applied to a retrospective test cohort in an EHR data warehouse at a
      large Veterans Affairs facility, and manual record reviews were used to validate
      each individual criterion. The final algorithm aimed at detecting an absence of
      timely follow-up was retrospectively applied to an independent validation cohort
      to determine the positive predictive value (PPV). Trigger performance, time to
      follow-up, reasons for lack of follow-up, and cancer outcomes were analyzed and
      reported by using descriptive statistics. Results The trigger algorithm was
      retrospectively applied to the records of 89 168 patients seen between January 1,
      2009, and December 31, 2009. Of 538 records with an imaging report that was
      flagged as suspicious for malignancy, 131 were identified by the trigger as being
      high risk for delayed diagnostic evaluation. Manual chart reviews confirmed a
      true absence of follow-up in 75 cases (trigger PPV of 57.3% for detecting
      evaluation delays), of which four received a diagnosis of primary lung cancer
      within the subsequent 2 years. Conclusion EHR-based triggers can be used to
      identify patients with suspicious imaging findings in whom follow-up diagnostic
      evaluation was delayed. ((c)) RSNA, 2015. 

PMID- 25961632
TI  - CT-Definable Subtypes of Chronic Obstructive Pulmonary Disease: A Statement of
      the Fleischner Society.
AB  - The purpose of this statement is to describe and define the phenotypic
      abnormalities that can be identified on visual and quantitative evaluation of
      computed tomographic (CT) images in subjects with chronic obstructive pulmonary
      disease (COPD), with the goal of contributing to a personalized approach to the
      treatment of patients with COPD. Quantitative CT is useful for identifying and
      sequentially evaluating the extent of emphysematous lung destruction, changes in
      airway walls, and expiratory air trapping. However, visual assessment of CT scans
      remains important to describe patterns of altered lung structure in COPD. The
      classification system proposed and illustrated in this article provides a
      structured approach to visual and quantitative assessment of COPD. Emphysema is
      classified as centrilobular (subclassified as trace, mild, moderate, confluent,
      and advanced destructive emphysema), panlobular, and paraseptal (subclassified as
      mild or substantial). Additional important visual features include airway wall
      thickening, inflammatory small airways disease, tracheal abnormalities,
      interstitial lung abnormalities, pulmonary arterial enlargement, and
      bronchiectasis.

PMID- 25961635
TI  - Evaluation of unique elastic aggregates (elastic globes) in normal facial skin by
      multiphoton laser scanning tomography.
AB  - BACKGROUND: There is no reliable marker to estimate the degree of skin aging in
      vivo. It now has become possible to quantitatively determine the dermal
      characteristics of the extracellular matrix (ECM) in vivo using multiphoton laser
      tomography (MLT). METHODS: Fifty-seven healthy Japanese female volunteers, aged
      from 20 to 60 years old, were examined using multiphoton depth-resolved
      measurements of autofluorescence (AF) and second harmonic generation (SHG) at
      three sites on their right cheek. Paraffin-embedded skin specimens obtained from
      the faces of 12 normal individuals aged 38-68 years old were stained with
      Elastica van Gieson (EVG). RESULTS: We found unique elastic aggregates at a 20
      MUm depth from the dermo-epidermal junction (DEJ) in vivo which increased in size
      with aging of subjects from 20 to 60 years old. SHG fibers seemed to surround
      those elastic aggregates. Histological examination of specimens from normal
      individuals stained with EVG confirmed the occurrence of elastic aggregates with
      varied sizes just beneath the epidermis or hair follicles. CONCLUSIONS: The
      elastic aggregates are morphologically similar to previously described 'elastic
      globes' and can serve as a marker of the early stage of photoaging. MLT will
      contribute to determine age-related dermal changes using a non-invasive
      technique.

PMID- 25961637
TI  - Lexical Preactivation in Basic Linguistic Phrases.
AB  - Many previous studies have shown that predictable words are read faster and lead
      to reduced neural activation, consistent with a model of reading in which words
      are activated in advance of being encountered. The nature of such preactivation,
      however, has typically been studied indirectly through its subsequent effect on
      word recognition. Here, we use magnetoencephalography to study the dynamics of
      prediction within serially presented adjective-noun phrases, beginning at the
      point at which the predictive information is first available to the reader. Using
      corpus transitional probability to estimate the predictability of a noun, we
      found an increase in activity in the left middle temporal gyrus in response to
      the presentation of highly predictive adjectives (i.e., adjectives that license a
      strong noun prediction). Moreover, we found that adjective predictivity and
      expected noun frequency interacted, such that the response to the highly
      predictive adjectives (e.g., stainless) was modulated by the frequency of the
      expected noun (steel). These results likely reflect preactivation of nouns in
      highly predictive contexts. The fact that the preactivation process was modulated
      by the frequency of the predicted item is argued to provide support for a
      frequency-sensitive lexicon. 

PMID- 25961636
TI  - Analysis of DNA methylation and gene expression in radiation-resistant head and
      neck tumors.
AB  - Resistance to radiation therapy constitutes a significant challenge in the
      treatment of head and neck squamous cell cancer (HNSCC). Alteration in DNA
      methylation is thought to play a role in this resistance. Here, we analyzed DNA
      methylation changes in a matched model of radiation resistance for HNSCC using
      the Illumina HumanMethylation450 BeadChip. Our results show that compared to
      radiation-sensitive cells (SCC-61), radiation-resistant cells (rSCC-61) had a
      significant increase in DNA methylation. After combining these results with
      microarray gene expression data, we identified 84 differentially methylated and
      expressed genes between these 2 cell lines. Ingenuity Pathway Analysis revealed
      ILK signaling, glucocorticoid receptor signaling, fatty acid alpha-oxidation, and
      cell cycle regulation as top canonical pathways associated with radiation
      resistance. Validation studies focused on CCND2, a protein involved in cell cycle
      regulation, which was identified as hypermethylated in the promoter region and
      downregulated in rSCC-61 relative to SCC-61 cells. Treatment of rSCC-61 and SCC
      61 with the DNA hypomethylating agent 5-aza-2'deoxycitidine increased CCND2
      levels only in rSCC-61 cells, while treatment with the control reagent cytosine
      arabinoside did not influence the expression of this gene. Further analysis of
      HNSCC data from The Cancer Genome Atlas found increased methylation in radiation
      resistant tumors, consistent with the cell culture data. Our findings point to
      global DNA methylation status as a biomarker of radiation resistance in HNSCC,
      and suggest a need for targeted manipulation of DNA methylation to increase
      radiation response in HNSCC. 

PMID- 25961638
TI  - Functional Connectivity under Anticipation of Shock: Correlates of Trait Anxious
      Affect versus Induced Anxiety.
AB  - Sustained anxiety about potential future negative events is an important feature
      of anxiety disorders. In this study, we used a novel anticipation of shock
      paradigm to investigate individual differences in functional connectivity during
      prolonged threat of shock. We examined the correlates of between-participant
      differences in trait anxious affect and induced anxiety, where the latter
      reflects changes in self-reported anxiety resulting from the shock manipulation.
      Dissociable effects of trait anxious affect and induced anxiety were observed.
      Participants with high scores on a latent dimension of anxious affect showed less
      increase in ventromedial pFC-amygdala connectivity between periods of safety and
      shock anticipation. Meanwhile, lower levels of induced anxiety were linked to
      greater augmentation of dorsolateral pFC-anterior insula connectivity during
      shock anticipation. These findings suggest that ventromedial pFC-amygdala and
      dorsolateral pFC-insula networks might both contribute to regulation of sustained
      fear responses, with their recruitment varying independently across participants.
      The former might reflect an evolutionarily old mechanism for reducing fear or
      anxiety, whereas the latter might reflect a complementary mechanism by which
      cognitive control can be implemented to diminish fear responses generated due to
      anticipation of aversive stimuli or events. These two circuits might provide
      complementary, alternate targets for exploration in future pharmacological and
      cognitive intervention studies. 

PMID- 25961639
TI  - A Common Polymorphism in SCN2A Predicts General Cognitive Ability through Effects
      on PFC Physiology.
AB  - Here we provide novel convergent evidence across three independent cohorts of
      healthy adults (n = 531), demonstrating that a common polymorphism in the gene
      encoding the alpha2 subunit of neuronal voltage-gated type II sodium channels
      (SCN2A) predicts human general cognitive ability or "g." Using meta-analysis, we
      demonstrate that the minor T allele of a common polymorphism (rs10174400) in
      SCN2A is associated with significantly higher "g" independent of gender and age.
      We further demonstrate using resting-state fMRI data from our discovery cohort (n
      = 236) that this genetic advantage may be mediated by increased capacity for
      information processing between the dorsolateral PFC and dorsal ACC, which support
      higher cognitive functions. Collectively, these findings fill a gap in our
      understanding of the genetics of general cognitive ability and highlight a
      specific neural mechanism through which a common polymorphism shapes
      interindividual variation in "g." 

PMID- 25961641
TI  - As Working Memory Grows: A Developmental Account of Neural Bases of Working
      Memory Capacity in 5- to 8-Year Old Children and Adults.
AB  - Working memory develops slowly: Even by age 8, children are able to maintain only
      half the number of items that adults can remember. Neural substrates that support
      performance on working memory tasks also have a slow developmental trajectory and
      typically activate to a lesser extent in children, relative to adults. Little is
      known about why younger participants elicit less neural activation. This may be
      due to maturational differences, differences in behavioral performance, or both.
      Here we investigate the neural correlates of working memory capacity in children
      (ages 5-8) and adults using a visual working memory task with parametrically
      increasing loads (from one to four items) using fMRI. This task allowed us to
      estimate working memory capacity limit for each group. We found that both age
      groups increased the activation of frontoparietal networks with increasing
      working memory loads, until working memory capacity was reached. Because
      children's working memory capacity limit was half of that for adults, the plateau
      occurred at lower loads for children. Had a parametric increase in load not been
      used, this would have given an impression of less activation overall and less
      load-dependent activation for children relative to adults. Our findings suggest
      that young children and adults recruit similar frontoparietal networks at working
      memory loads that do not exceed capacity and highlight the need to consider
      behavioral performance differences when interpreting developmental differences in
      neural activation. 

PMID- 25961640
TI  - Electrophysiological Correlates of Refreshing: Event-related Potentials
      Associated with Directing Reflective Attention to Face, Scene, or Word
      Representations.
AB  - Refreshing is the component cognitive process of directing reflective attention
      to one of several active mental representations. Previous studies using fMRI
      suggested that refresh tasks involve a component process of initiating refreshing
      as well as the top-down modulation of representational regions central to
      refreshing. However, those studies were limited by fMRI's low temporal
      resolution. In this study, we used EEG to examine the time course of refreshing
      on the scale of milliseconds rather than seconds. ERP analyses showed that a
      typical refresh task does have a distinct electrophysiological response as
      compared to a control condition and includes at least two main temporal
      components: an earlier (~400 msec) positive peak reminiscent of a P3 response and
      a later (~800-1400 msec) sustained positivity over several sites reminiscent of
      the late directing attention positivity. Overall, the evoked potentials for
      refreshing representations from three different visual categories (faces, scenes,
      words) were similar, but multivariate pattern analysis showed that some category
      information was nonetheless present in the EEG signal. When related to previous
      fMRI studies, these results are consistent with a two-phase model, with the first
      phase dominated by frontal control signals involved in initiating refreshing and
      the second by the top-down modulation of posterior perceptual cortical areas that
      constitutes refreshing a representation. This study also lays the foundation for
      future studies of the neural correlates of reflective attention at a finer
      temporal resolution than is possible using fMRI. 

PMID- 25961642
TI  - Anti-Inflammatory Activity in the Low Molecular Weight Fraction of Commercial
      Human Serum Albumin (LMWF5A).
AB  - The innate immune system is increasingly being recognized as a critical component
      in osteoarthritis (OA) pathophysiology. An ex vivo immunoassay utilizing human
      peripheral blood mononuclear cells (PBMC) was developed in order to assess the OA
      anti-inflammatory properties of the low molecular weight fraction (<5 kDa) of
      commercial human serum albumin (LMWF5A). PBMC from various donors were pre
      incubated with LMWF5A before LPS stimulation. TNFalpha release was measured by
      ELISA in supernatants after an overnight incubation. A >= 30% decrease in
      TNFalpha release was observed. This anti-inflammatory effect is potentially
      useful in assessing potency of LMWF5A for the treatment of OA. 

PMID- 25961643
TI  - The psychologist's role in transgender-specific care with U.S. veterans.
AB  - Psychologists are integral to the care of transgender individuals. This article
      details the many roles for psychologists in transgender-specific care, including
      diagnosing and treating gender dysphoria; providing treatment for comorbid
      conditions; referring to medical services such as gender confirmation surgeries,
      voice modification, and cross-sex hormone therapies; serving as consultants
      within health care systems; and advocating for addressing barriers in systems in
      which transgender individuals live and work. Transgender veterans have unique
      experiences and vulnerabilities related to their military service that are
      detailed from a review of the literature, and we make the case that Veterans
      Health Administration (VHA) and community psychologists are well-positioned to
      provide care to transgender veterans (trans-vets). In this article, the authors
      describe the experiences that many trans-vets have faced, identify the importance
      of treatment for gender dysphoria (and draw the distinction between gender
      identity disorder and gender dysphoria) as well as psychologists' roles, and
      clarify which transgender-related services are available to eligible veterans
      though VHA per policy and how VHA providers have access to training to provide
      that care. In addition, we describe how veterans can connect to the VHA, even if
      they have (and want to continue working with) non-VHA psychologists or other
      community providers.

PMID- 25961644
TI  - The Blackfeet Indian culture camp: Auditioning an alternative indigenous
      treatment for substance use disorders.
AB  - American Indian and Alaska Native (AIAN) communities experience alarming health
      disparities, including high rates of substance use disorders (SUDs).
      Psychological services for AIANs, including SUDs treatment, are primarily funded
      by the federal Indian Health Service and typically administered by tribal
      governments. Tribal administration of SUDs treatment programs has routinely
      involved either inclusion of traditional cultural practices into program
      activities or adaptation of conventional treatment approaches to distinctive
      community sensibilities. In this article, we investigate a third possibility: the
      collaborative, community-based development of an alternative indigenous
      intervention that was implemented as a form of SUDs treatment in its own right
      and on its own terms. Specifically, in July of 2012, we undertook a trial
      implementation of a seasonal cultural immersion camp based on traditional Pikuni
      Blackfeet Indian cultural practices for 4 male clients from the reservation's
      federally funded SUDs treatment program. Given a variety of logistical and
      methodological constraints, the pilot offering of the culture camp primarily
      served as a demonstration of "proof of concept" for this alternative indigenous
      intervention. In presenting and reflecting on this effort, we consider many
      challenges associated with alternative indigenous treatment models, especially
      those associated with formal outcome evaluation. Indeed, we suggest that the
      motivation for developing local indigenous alternatives for AIAN SUDs treatment
      may work at cross-purposes to the rigorous assessment of therapeutic efficacy for
      such interventions. Nevertheless, we conclude that these efforts afford ample
      opportunities for expanding the existing knowledge base concerning the delivery
      of community-based psychological services for AIANs.

PMID- 25961646
TI  - The Mokihana Program: The effectiveness of an integrated department of education
      and department of health school-based behavioral health approach.
AB  - As a result of difficulties with access to care and resulting low levels of
      service utilization, the mental health problems of children often go undiagnosed
      and untreated. One of the most promising approaches to increasing access to care
      is the delivery of mental health services in school settings, where almost all of
      the children in a community can be accessed. However, as a result of competing
      needs, cultures, and objectives, integrating mental health services into schools
      can be challenging. In the wake of a devastating hurricane in 1992 and efforts to
      identify and treat children with posttraumatic stress, many of these barriers
      were overcome on the island of Kauai, Hawaii and led to the development of the
      Mokihana Program, an integrated Department of Education and Hawaii Department of
      Health initiative for providing school-based behavioral health services. This
      study examined the effectiveness of the Mokihana Program in the treatment of 123
      elementary age children and 56 adolescents by comparing teacher ratings of
      behavior problems and adaptive skills at intake and at 1-year follow-up. It was
      hypothesized that symptom severity would decrease from pretreatment to follow-up.
      Findings showed statistically significant improvements across a wide spectrum of
      behavioral problems and adaptive functioning. The authors explore the challenges
      and opportunities in sustaining and replicating this type of departmental
      integration in the service of children and youth.

PMID- 25961645
TI  - How do providers serving American Indians and Alaska Natives with substance abuse
      problems define evidence-based treatment?
AB  - Rates of substance abuse remain high in American Indian and Alaska Native (AI/AN)
      populations. While there are many evidence-based treatments (EBTs) for substance
      use problems, no studies exist describing how directors of treatment programs
      serving AI/ANs perceive and use EBTs. Twenty-one key informant interviews with
      program administrators and 10 focus groups with clinicians were conducted at 18
      treatment programs for AI/ANs with substance use problems. Demographic data were
      not collected to protect participant privacy. Transcripts were coded to identify
      relevant themes. A majority of participants correctly defined an EBT using the
      key terms "effective" and "research" found in standard definitions of the phrase.
      More detailed descriptions were uncommon. Prevalent themes related to attitudes
      about EBTs included concerns about cultural relevance, external mandates to use
      EBTs, and their reliance on western conceptualization of substance abuse. While
      most administrators and clinicians who treat AI/AN clients for substance abuse
      had a basic understanding of what constitutes an EBT, there was little consensus
      regarding their relevance for use with AI/ANs. Recognizing that broad geographic
      and tribal diversity among AI/AN populations may impact conclusions drawn about
      EBTs, several factors may enhance the abilities of program staff to identify EBTs
      most appropriate for local implementation. These include gaining a more detailed
      understanding of how an EBT is developed and how to assess its scientific
      grounding, as well as utilizing definitions of EBTs that include not only
      research evidence, but also clinical expertise and judgment, and fit with
      consumer choice, preference, and culture.

PMID- 25961647
TI  - Quality of care in American Indian child and adolescent behavioral health: A
      pilot study of patient and family perspectives.
AB  - Research regarding the quality of behavioral health care for American Indian (AI)
      children and adolescents is extremely limited, and no study has considered the
      qualitative perspectives of the AI children receiving such services or that of
      their families. This pilot study investigated AI patient and family perspectives
      of what quality of care means to them. Data were drawn from interviews of parents
      (n = 15) and the youth (if they were age 11 or older; n = 11) of 16 children and
      adolescents who received treatment at three behavioral health programs serving AI
      communities. Interview transcripts were coded and analyzed for key themes that
      related to treatment structure, process, and outcomes. According to these
      participants, the principal indicator of treatment quality was "being able to
      trust the clinician." The most valued treatment outcomes for improvement were the
      youth's "self-efficacy and self-worth," "functioning in school," and
      "relationship with the family." Future research is needed on how to best
      integrate these domains into specific and objective indicators for standardized
      quality of care assessments of AI child and adolescent behavioral health
      services.

PMID- 25961648
TI  - Cultural adaptation, psychometric properties, and outcomes of the Native American
      Spirituality Scale.
AB  - Spirituality is central to many Native Americans (NAs) and has been associated
      with recovery from substance use disorders (SUDs). However, no published
      questionnaire uniquely taps tribal-specific spiritual beliefs and practices. This
      hinders efforts to integrate traditional NA spirituality into SUD treatment and
      track spiritual outcomes. As part of a randomized controlled trial examining SUD
      treatment for NAs, we adapted the Daily Spiritual Experience Scale (DSES) in
      collaboration with members of a Southwest tribe to create the Native American
      Spirituality Scale (NASS) and measured changes in the NASS over the course of
      treatment. The 83 participants (70% male) were from a single Southwest tribe and
      seeking SUD treatment. They completed the NASS at baseline, 4, 8, and 12 months.
      Exploratory factor analysis of the NASS was conducted and its temporal
      invariance, construct validity, and longitudinal changes in the factor and item
      scores were examined. The NASS yielded a 2-factor structure that was largely
      invariant across time. Factor 1 reflected behavioral practices, while Factor 2
      reflected more global beliefs. Both factors significantly increased across 12
      months, albeit at different assessment points. At baseline, Factor 1 was
      negatively related to substance use and positively associated with measures of
      tribal identification while Factor 2 was unrelated to these measures. Given the
      importance of tribal spirituality to many NAs, the development of this
      psychometrically sound measure is a key precursor and complement to the
      incorporation of tribal spirituality into treatment, as well as research on
      mechanisms of change for SUD treatment among NAs and assessment of NA
      spirituality in relation to other aspects of health.

PMID- 25961649
TI  - The impact of demographic differences on native veterans' outpatient service
      utilization.
AB  - Many Native veterans--including American Indian/Alaska Native (AIAN) and Native
      Hawaiian/Pacific Islanders (NHPI)--have served in the United States Armed Forces.
      Most of these veterans are eligible for medical care from the Department of
      Veterans Affairs (VA), but research examining the determinants of their service
      use is needed to inform policy and allocate appropriate resources for these
      unique groups. In a retrospective cohort study, we examined the impact of Native
      veterans' personal demographics on their outpatient utilization of VA-based
      primary care and mental health services. AIAN (n = 37,687) and NHPI (n = 46,582)
      veterans were compared with a non-Native reference (N = 262,212) using logistic
      and binomial regression. AIAN and NHPIs were more likely to be female, report
      military sexual trauma, and utilize the VA for posttraumatic stress disorder,
      traumatic brain injury, depression, addiction, anxiety, hypertension, and
      diabetes care. More AIAN and urban NHPI veterans served in Iraq and Afghanistan,
      and Native women reported more military sexual trauma than their non-Native
      counterparts. Primary care and mental health services were associated with race,
      number of diagnoses, and disability ratings. For mental health services, service
      era, military sexual trauma, and marital status were related to service
      utilization. Native veterans' medical need was elevated for primary and mental
      health care. Rural residence was associated with less mental health use. The
      findings underscore the need for additional specialized services in rural areas,
      more targeted outreach to Operation Enduring Freedom/Operation Iraqi Freedom
      Native veterans, and additional care directed toward Native women's health care
      needs.

PMID- 25961650
TI  - Racial-ethnic differences in access, diagnosis, and outcomes in public-sector
      inpatient mental health treatment.
AB  - This study investigated inequities in access, diagnosis, and treatment for
      African Americans and Hispanic Americans receiving treatment in northeast, public
      sector, inpatient mental health settings as part of a Department of Mental Health
      and Addiction Services Health Disparities Initiative. Data from 1,484 adults were
      obtained through a random extract of patients admitted to state inpatient
      facilities between 2002 and 2005. After controlling for demographic variables and
      symptom severity, logistic and linear regression showed that Hispanic Americans
      were significantly more likely to enter inpatient care through crisis/emergency
      sources and were significantly less likely to self-refer or come to inpatient
      care through other sources (e.g., family, outpatient). After admission, Hispanic
      Americans were more likely to be diagnosed with other psychotic disorders (e.g.,
      schizoaffective disorder, delusional disorder), were less likely to receive an
      Axis II diagnosis at discharge, and had a shorter length of stay than non
      Hispanic White Americans. African Americans were more likely than other groups to
      be diagnosed with schizophrenia, drug-related, and Cluster B diagnoses (discharge
      only), and they were less likely to be diagnosed with mood disorders and other
      nonpsychotic disorders. Although African Americans were more likely than other
      groups to come to inpatient units from numerous routes, including self-referral
      and referral from other sources (e.g., family, outpatient), they were more likely
      to terminate treatment against medical advice and displayed shorter length of
      stay despite receiving ratings of greater symptom severity at discharge. These
      findings highlight the need for policies, programs, and system interventions
      designed to eliminate disparities and improve the quality and cultural
      responsiveness of behavioral health services.

PMID- 25961651
TI  - No costly prosociality among related long-tailed macaques (Macaca fascicularis).
AB  - Altruism, benefiting another at a cost to the donor, may be achieved through
      prosocial behavior. Studies of nonhuman animals typically investigate prosocial
      behavior with paradigms in which the donor can choose to give a recipient a food
      item, and the choice does not affect the donor's reward (which is either present
      or absent). In such tasks, long-tailed macaques (Macaca fascicularis) show
      prosocial behavior, especially toward kin. Here, we tested captive long-tailed
      macaques with related recipients in an alternative task, in which the donor had
      to give up a preferred reward to benefit the recipient; that is, they had to
      choose a lower valued reward for themselves to provide food to their kin.
      Overall, the macaques did not provide their kin with food. The task forced the
      donor to balance its prosocial behavior with its selfish choice for a higher
      value reward, a balance that turned out to favor selfish motives. Consequently,
      our study shows that a prosocial tendency is not sufficient to elicit costly
      prosocial behavior in long-tailed macaques. Subsequently, we feel that tasks in
      which the donor must choose a lower value reward to benefit another individual
      may allow the titration of the strength of prosocial behavior, and thus provides
      interesting possibilities for future comparative studies.

PMID- 25961652
TI  - Contraversive neglect? A modulation of visuospatial neglect in association with
      contraversive pushing.
AB  - OBJECTIVE: Contraversive pushing (CP) is a neurologic disorder characterized by a
      lateral postural imbalance. Pusher patients actively push toward their
      contralesional side due to a misperception of the body's orientation in relation
      to gravity. Although not every patient with CP suffers from spatial neglect (SN),
      both phenomena are highly correlated in right-hemispheric patients. The present
      study investigates whether peripersonal visuospatial functioning differs in
      neglect patients with versus without CP (NP+ vs. NP- patients). METHOD: Eighteen
      right-hemispheric stroke patients with SN were included, of which 17 in a double
      blind case-control study and 1 single case with posterior pushing to supplement
      the discourse. A computer-based visuospatial navigation task, in which
      lateralized deviation can freely emerge, was used to quantify visuospatial
      behavior. In addition, visuospatial orienting was monitored using line bisection.
      RESULTS: Significant intergroup differences were found. The NP+ patients
      demonstrated a smaller ipsilesional navigational deviation and more cross-over
      (contralesional instead of ipsilesional deviation) in long line bisection. As
      such, they demonstrated a contraversive (contralesionally directed) shift in
      comparison with the NP- patients. CONCLUSIONS: These findings highlight the
      similarity between 2 systems of space representation. They are consistent with a
      coherence between the neural processing system that mainly provides for postural
      control, and the one responsible for nonpredominantly postural, visuospatial
      behavior.

PMID- 25961653
TI  - Diffuse Large B-Cell Lymphoma of the Peri-Implant Mucosa Mimicking Peri
      Implantitis.

PMID- 25961654
TI  - Reproducibility of parameter learning with missing observations in naive Wnt
      Bayesian network trained on colorectal cancer samples and doxycycline-treated
      cell lines.
AB  - In this manuscript the reproducibility of parameter learning with missing
      observations in a naive Bayesian network and its effect on the prediction results
      for Wnt signaling activation in colorectal cancer is tested. The training of the
      network is carried out separately on doxycycline-treated LS174T cell lines
      (GSE18560) as well as normal and adenoma samples (GSE8671). A computational
      framework to test the reproducibility of the parameters is designed in order
      check the veracity of the prediction results. Detailed experimental analysis
      suggests that the prediction results are accurate and reproducible with
      negligible deviations. Anomalies in estimated parameters are accounted for due to
      the representation issues of the Bayesian network model. High prediction
      accuracies are reported for normal (N) and colon-related adenomas (AD),
      colorectal cancer (CRC), carcinomas (C), adenocarcinomas (ADC) and replication
      error colorectal cancer (RER CRC) test samples. Test samples from inflammatory
      bowel diseases (IBD) do not fare well in the prediction test. Also, an
      interesting case regarding hypothesis testing came up while proving the
      statistical significance of the different design setups of the Bayesian network
      model. It was found that hypothesis testing may not be the correct way to check
      the significance between design setups, especially when the structure of the
      model is the same, given that the model is trained on a single piece of test
      data. The significance test does have value when the datasets are independent.
      Finally, in comparison to the biologically inspired models, the naive Bayesian
      model may give accurate results, but this accuracy comes at the cost of a loss of
      crucial biological knowledge which might help reveal hidden relations among
      intra/extracellular factors affecting the Wnt pathway. 

PMID- 25961655
TI  - Masitinib for the treatment of mild to moderate Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a degenerative neurological disorder that is the most
      common cause of dementia and disability in older patients. Available treatments
      are symptomatic in nature and are only sufficient to improve the quality of life
      of AD patients temporarily. A potential strategy, currently under investigation,
      is to target cell-signaling pathways associated with neurodegeneration, in order
      to decrease neuroinflammation, excitotoxicity, and to improve cognitive
      functions. Current review centers on the role of neuroinflammation and the
      specific contribution of mast cells to AD pathophysiology. The authors look at
      masitinib therapy and the evidence presented through preclinical and clinical
      trials. Dual actions of masitinib as an inhibitor of mast cell-glia axis and a
      Fyn kinase blocker are discussed in the context of AD pathology. Masitinib is in
      Phase III clinical trials for the treatment of malignant melanoma, mastocytosis,
      multiple myeloma, gastrointestinal cancer and pancreatic cancer. It is also in
      Phase II/III clinical trials for the treatment of multiple sclerosis, rheumatoid
      arthritis and AD. Additional research is warranted to better investigate the
      potential effects of masitinib in combination with other drugs employed in AD
      treatment. 

PMID- 25961656
TI  - Towards zero-power ICT.
AB  - Is it possible to operate a computing device with zero energy expenditure? This
      question, once considered just an academic dilemma, has recently become strategic
      for the future of information and communication technology. In fact, in the last
      forty years the semiconductor industry has been driven by its ability to scale
      down the size of the complementary metal-oxide semiconductor-field-effect
      transistor, the building block of present computing devices, and to increase
      computing capability density up to a point where the power dissipated in heat
      during computation has become a serious limitation. To overcome such a
      limitation, since 2004 the Nanoelectronics Research Initiative has launched a
      grand challenge to address the fundamental limits of the physics of switches. In
      Europe, the European Commission has recently funded a set of projects with the
      aim of minimizing the energy consumption of computing. In this article we briefly
      review state-of-the-art zero-power computing, with special attention paid to the
      aspects of energy dissipation at the micro- and nanoscales. 

PMID- 25961657
TI  - The Role of HIT in Care Coordination in the United States.

PMID- 25961658
TI  - In reply.

PMID- 25961659
TI  - Does good medication adherence really save payers money?
AB  - BACKGROUND: Despite a growing consensus that better adherence with evidence-based
      medications can save payers money, assertions of cost offsets may be incomplete
      if they fail to consider additional drug costs and/or are biased by healthy
      adherer behaviors unobserved in typical medical claims-based analyses.
      OBJECTIVES: The objective of this study was to determine whether controlling for
      healthy adherer bias (HAB) materially affected estimated medical cost offsets and
      additional drug spending associated with higher adherence. SUBJECTS: A total of
      1273 Medicare beneficiaries with diabetes enrolled in Part D plans between 2006
      and 2009. RESEARCH DESIGN: Using survey and claims data from the Medicare Current
      Beneficiary Survey, we measured medical and drug costs associated with good and
      poor adherence (proportion of days covered >= 80% and <80%, respectively) to oral
      antidiabetic drugs, ACE inhibitors/ARBs, and statins over 2 years. To test for
      HAB, we estimated pairs of regression models, one set containing variables
      typically controlled for in conventional claims analysis and a second set with
      survey-based variables selected to capture HAB effects. RESULTS: We found
      consistent evidence that controlling for HAB reduces estimated savings in medical
      costs from better adherence, and likewise, reduces estimates of additional
      adherence-related drug spending. For ACE inhibitors/ARBs we estimate that
      controlling for HAB reduced adherence-related medical cost offsets from $6389 to
      $4920 per person (P<0.05). Estimates of additional adherence-related drug costs
      were 26% and 14% lower in HAB-controlled models (P < 0.05). CONCLUSIONS: These
      results buttress the economic case for action by health care payers to improve
      medication adherence among insured persons with chronic disease. However, given
      the limitations of our research design, further research on larger samples with
      other disease states is clearly warranted.

PMID- 25961660
TI  - How does geographic access affect in-hospital mortality for veterans with acute
      ischemic stroke?
AB  - OBJECTIVE: To examine the relationship between estimated travel time to admitting
      hospital and mortality for veterans with acute ischemic stroke, controlling for
      patient demographic, clinical, facility-level variables, as well as select in
      hospital treatments and procedures. METHODS: A longitudinal observational
      population-based study. Information on all veterans discharged from a Veterans
      Administration Medical Center (VAMC) with an ischemic stroke diagnosis between
      October 1, 2006 and September 30, 2008 were examined. A total of 10,430 patients
      met the inclusion criteria for the study. Unadjusted differences between patients
      who died during the hospital stay versus those patients who were discharged
      alive, used chi analyses or Student t tests, as appropriate. Multivariable
      logistic regression was used to control for confounding effects of patient,
      treatment, and facility characteristics to examine the relationship between
      travel time and the bivariate outcome of in-hospital mortality. RESULTS: Travel
      time to the admitting VAMC, our primary variable of interest regarding the effect
      on in-hospital mortality, after adjusting for the patient, treatment, and
      facility characteristics showed that longer travel times significantly increased
      the odds of in-hospital mortality. Travel times >= 90 minutes had increased odds
      of in-hospital mortality (OR=1.476; 95% CI, 1.067-2.042) as compared with <30
      minutes. CONCLUSIONS: Even after adjusting for the confounding effects of
      patient, treatment, and facility characteristics, travel time from home to
      admitting VAMC was significantly associated with in-hospital mortality.

PMID- 25961661
TI  - Do hospital service areas and hospital referral regions define discrete health
      care populations?
AB  - BACKGROUND: Effective measurement of health care quality, access, and cost for
      populations requires an accountable geographic unit. Although Hospital Service
      Areas (HSAs) and Hospital Referral Regions (HRRs) have been extensively used in
      health services research, it is unknown whether these units accurately describe
      patterns of hospital use for patients living within them. OBJECTIVES: To evaluate
      the ability of HSAs, HRRs, and counties to define discrete health care
      populations. RESEARCH DESIGN: Cross-sectional geographic analysis of hospital
      admissions. SUBJECTS: All hospital admissions during the year 2011 in Washington,
      Arizona, and Florida. MEASURES: The main outcomes of interest were 3 metrics that
      describe patient movement across HSA, HRR, and county boundaries: localization
      index, market share index, and net patient flow. Regression models tested the
      association of these metrics with different HSA characteristics. RESULTS: For 45%
      of HSAs, fewer than half of the patients were admitted to hospitals located in
      their HSA of residence. For 16% of HSAs, more than half of the treated patients
      lived elsewhere. There was an equivalent degree of movement across county
      boundaries but less movement across HRR boundaries. Patients living in populous,
      urban HSAs with multiple, large, and teaching hospitals tended to remain for
      inpatient care. Patients admitted through the emergency department tended to
      receive care at local hospitals relative to other patients. CONCLUSIONS: HSAs and
      HRRs are geographic units commonly used in health services research yet vary in
      their ability to describe where patients receive hospital care. Geographic models
      may need to account for differences between emergent and nonemergent care.

PMID- 25961662
TI  - Fragment-Based QSAR and Structural Analysis of a Series of Hydroxyethylamine
      Derivatives as HIV-1 Protease Inhibitors.
AB  - HIV-1 protease is a key enzyme for viral maturation because it cleaves precursor
      polypeptides into mature structural and functional proteins. The introduction of
      protease inhibitors into therapy in the mid-1990s has dramatically changed the
      AIDS panorama worldwide. However, resistance to currently available protease
      inhibitors remains a serious challenge that must be overcome. Herein, we report a
      fragment-based QSAR study of a series of highly potent HIV-1 protease inhibitors,
      as well as the structural basis of their binding affinity. Hologram QSAR (HQSAR)
      analyses were performed, resulting in robust statistical models that consistently
      correlated the bioactivity profile with the two dimensional molecular
      descriptors. The robustness of the best model was assessed based on the
      correlation coefficients (q(2) = 0.70 and r(2) = 0.90), as well as the prediction
      of the activity of an external test set (r(2) pred = 0.75). Structure-based
      molecular modeling studies were performed to investigate the binding mode of the
      best inhibitor in the active site of the enzyme. The HQSAR model and the
      structural findings provide valuable insights for the rational design of
      structurally related HIV-1 protease inhibitors.

PMID- 25961663
TI  - Comprehensive evaluation of antibiotics emission and fate in the river basins of
      China: source analysis, multimedia modeling, and linkage to bacterial resistance.
AB  - Antibiotics are widely used in humans and animals, but there is a big concern
      about their negative impacts on ecosystem and human health after use. So far
      there is a lack of information on emission inventory and environmental fate of
      antibiotics in China. We studied national consumption, emissions, and multimedia
      fate of 36 frequently detected antibiotics in China by market survey, data
      analysis, and level III fugacity modeling tools. Based on our survey, the total
      usage for the 36 chemicals was 92700 tons in 2013, an estimated 54000 tons of the
      antibiotics was excreted by human and animals, and eventually 53800 tons of them
      entered into the receiving environment following various wastewater treatments.
      The fugacity model successfully predicted environmental concentrations (PECs) in
      all 58 river basins of China, which are comparable to the reported measured
      environmental concentrations (MECs) available in some basins. The bacterial
      resistance rates in the hospitals and aquatic environments were found to be
      related to the PECs and antibiotic usages, especially for those antibiotics used
      in the most recent period. This is the first comprehensive study which
      demonstrates an alarming usage and emission of various antibiotics in China. 

PMID- 25961664
TI  - Effects of bariatric surgery on incidence of obesity-related cancers: a meta
      analysis.
AB  - BACKGROUND: The aim of this meta-analysis was to investigate possible
      relationships between bariatric surgery and incidence of obesity-related cancers.
      Obesity is an established risk factor for obesity-related cancers but the effects
      of bariatric surgery on incidence of obesity-related cancers are uncertain.
      MATERIAL/METHODS: We searched 4 electronic databases to identify eligible
      studies: PubMed, Embase, Web of Science, and Google Scholar. Five observational
      studies were eligible and included in this meta-analysis. Random-effects or fixed
      effects odds ratio (OR) and its corresponding 95% confidence interval (CI) were
      pooled. RESULTS: Meta-analysis of these 5 observational studies revealed that
      bariatric surgery was associated with a significantly (p=0.0004) reduced
      incidence of obesity-related cancers (OR=0.43, 95%CI, 0.27-0.69) when compared
      with control individuals. Pooled estimated data showed that bariatric surgery is
      associated with a 24% lower colorectal cancer (CRC) risk. No publication bias was
      detected by Egger's or Begg's tests. CONCLUSIONS: Although bariatric surgery may
      significantly reduce incidence of obesity-related cancers, considering the
      limitations of these included studies, these findings should be confirmed by
      further well-designed studies.

PMID- 25961665
TI  - Adherence to diagnostic guidelines of hepatocellular carcinoma: 12-year
      experience in a veterans affairs medical center.
AB  - BACKGROUND: Noninvasive diagnostic criteria for cirrhotic hepatocellular
      carcinoma (HCC) were first established in 2001 by the European Association for
      the Study of the Liver. OBJECTIVES: The aim of this study was to evaluate
      adherence to the HCC diagnostic algorithm over time and identify factors
      associated with nonadherence. METHODS: Between 2001 and 2013, 224 consecutive
      cirrhotic HCC cases were retrospectively reviewed. Nonadherent biopsy (NAB) was
      defined as cases diagnosed either by biopsy despite meeting noninvasive criteria
      for HCC or by biopsy in place of an optional second imaging modality. Nonadherent
      nonbiopsy (NANB) was defined as cases diagnosed without performing biopsy when
      noninvasive criteria were not met. Factors associated with nonadherence were
      identified using multivariate analysis. RESULTS: Nonadherence rate decreased from
      52 to 30% over the study period (P = 0.003). Among all patients, there were 34%
      NAB and 13% NANB cases. Compared with the adherence group, both NAB and NANB
      groups were likely to undergo only computed tomography scanning [odds ratio (OR)
      3.08, 95% confidence interval (CI) 1.71-5.66 and OR 3.18, 95% CI 1.28-8.27,
      respectively] and were less likely to undergo MRI (OR 0.29, 95% CI 0.16-0.53 and
      OR 0.26, 95% CI 0.10-0.66, respectively). In addition, the NAB group was less
      likely to be presented in a multidisciplinary tumor conference (OR 0.12, 95% CI
      0.02-0.61). CONCLUSION: This is the first study to report adherence to HCC
      diagnostic guidelines over time in a veteran hospital. Despite overall
      improvement, nonadherence at the present time is still high (~ 30%).
      Underutilization of MRI and the multidisciplinary tumor conference is associated
      with nonadherence, representing a potential area for improvement.

PMID- 25961666
TI  - (30)Si mole fraction of a silicon material highly enriched in (28)Si determined
      by instrumental neutron activation analysis.
AB  - The latest determination of the Avogadro constant, carried out by counting the
      atoms in a pure silicon crystal highly enriched in (28)Si, reached the target 2 *
      10(-8) relative uncertainty required for the redefinition of the kilogram based
      on the Planck constant. The knowledge of the isotopic composition of the enriched
      silicon material is central; it is measured by isotope dilution mass
      spectrometry. In this work, an independent estimate of the (30)Si mole fraction
      was obtained by applying a relative measurement protocol based on Instrumental
      Neutron Activation Analysis. The amount of (30)Si isotope was determined by
      counting the 1266.1 keV gamma-photons emitted during the radioactive decay of the
      radioisotope (31)Si produced via the neutron capture reaction
      (30)Si(n,gamma)(31)Si. The x((30)Si) = 1.043(19) * 10(-6) mol mol(-1) is
      consistent with the value currently adopted by the International Avogadro
      Coordination. 

PMID- 25961668
TI  - Device Stability and Light-Soaking Characteristics of High-Efficiency
      Benzodithiophene-Thienothiophene Copolymer-Based Inverted Organic Solar Cells
      with F-TiO(x) Electron-Transport Layer.
AB  - Organic solar cells (OSC) based on low-band-gap thienothiophene-benzodithiophene
      copolymer have achieved relatively high efficiency (7-9%) in recent times. Among
      this class of material, poly({4,8-bis[(2-ethylhexyl)oxy]benzo[1,2-b:4,5
      b']dithiophene-2,6-diyl}{3-fluoro-2-[(2-ethylhexyl)carbonyl]thieno[3,4
      b]thiophenediyl}) (PTB-7) is one of the high-efficiency materials reported for
      OSC. However, this material seems to be intrinsically unstable compared to the
      commonly used workhorse polymer, poly(3-hexylthiophene) (P3HT), especially when
      illuminated in air. Inverted device architecture is usually adopted to improve
      device stability, but the device stability using PTB-7 is not yet well
      understood. In this work, a systematic degradation study on a PTB-7:PC71BM-based
      inverted OSC employing F-TiO(x) as electron-transport layer (ETL) was conducted
      for the first time. Air stability, photostability in inert atmosphere, and
      photostability under ambient conditions of the device were separately carried out
      to understand better the polymer behavior in inverted OSC. The device's air
      stability with different polymer absorber layers was studied by exposing the
      devices in air for up to 1500 h. Because of the long and easily cleavable alkoxy
      side chains in the polymer backbone, a PTB-7:PC71BM-based inverted OSC device is
      highly susceptible to oxygen and moisture when compared to a P3HT:PC61BM-based
      device. In addition, with the presence of F-TiO(x) ETL, a significant reduction
      in light-soaking time was also observed in PTB-7:PC71BM inverted OSC for the
      first time. The TiO(x)/organic interface was found to be responsible for the
      reduction in the light-soaking time.

PMID- 25961667
TI  - Effect of the rheological properties of carbon nanotube dispersions on the
      processing and properties of transparent conductive electrodes.
AB  - Transparent conductive films are made from aqueous surfactant stabilized
      dispersions of carbon nanotubes using an up-scalable rod coating method. The
      processability of the films is governed by the amount of surfactant which is
      shown to alter strongly the wetting and viscosity of the ink. The increase of
      viscosity results from surfactant mediated attractive interactions between the
      carbon nanotubes. Links between the formulation, ink rheological properties, and
      electro-optical properties of the films are determined. The provided guidelines
      are generalized and used to fabricate optimized electrodes using conductive
      polymers and carbon nanotubes. In these electrodes, the carbon nanotubes act as
      highly efficient viscosifiers that allow the optimized ink to be homogeneously
      spread using the rod coating method. From a general point of view and in contrast
      to previous studies, the CNTs are optimally used in the present approach as
      conductive additives for viscosity enhancements of electronic inks. 

PMID- 25961669
TI  - Evaluation and integration of cancer gene classifiers: identification and ranking
      of plausible drivers.
AB  - The number of mutated genes in cancer cells is far larger than the number of
      mutations that drive cancer. The difficulty this creates for identifying relevant
      alterations has stimulated the development of various computational approaches to
      distinguishing drivers from bystanders. We develop and apply an ensemble
      classifier (EC) machine learning method, which integrates 10 classifiers that are
      publically available, and apply it to breast and ovarian cancer. In particular we
      find the following: (1) Using both standard and non-standard metrics, EC almost
      always outperforms single method classifiers, often by wide margins. (2) Of the
      50 highest ranked genes for breast (ovarian) cancer, 34 (30) are associated with
      other cancers in either the OMIM, CGC or NCG database (P < 10(-22)). (3) Another
      10, for both breast and ovarian cancer, have been identified by GWAS studies. (4)
      Several of the remaining genes--including a protein kinase that regulates the Fra
      1 transcription factor which is overexpressed in ER negative breast cancer cells;
      and Fyn, which is overexpressed in pancreatic and prostate cancer, among others-
      are biologically plausible. Biological implications are briefly discussed. Source
      codes and detailed results are available at
      http://www.visantnet.org/misi/driver_integration.zip. 

PMID- 25961670
TI  - Low Temperature Vacuum Synthesis of Triangular CoO Nanocrystal/Graphene
      Nanosheets Composites with Enhanced Lithium Storage Capacity.
AB  - CoO nanocrystal/graphene nanosheets (GNS) composites, consisting of a triangular
      CoO nanocrystal of 2~20 nm on the surface of GNS, are synthesized by a mild
      synthetic method. First, cobalt acetate tetrahydrate is recrystallized in the
      alcohol solution at a low temperature. Then, graphene oxide mixed with cobalt
      precursor followed by high vacuum annealing to form the CoO nanocrystal/GNS
      composites. The CoO nanocrystal/GNS composites exhibit a high reversible capacity
      of 1481.9 m Ah g(-1) after 30 cycles with a high Coulombic efficiency of over 96%
      when used as anode materials for lithium ion battery. The excellent
      electrochemical performances may be attributed to the special structure of the
      composites. The well-dispersed triangular CoO nanocrystal on the substrate of
      conductive graphene can not only have a shorter diffusion length for lithium
      ions, better stress accommodation capability during the charge-discharge
      processes and more accessible active sites for lithium-ion storage and
      electrolyte wetting, but also possess a good conductive network, which can
      significantly improve the whole electrochemical performance. 

PMID- 25961672
TI  - Detection of residual oil-sand-derived organic material in developing soils of
      reclamation sites by ultra-high-resolution mass spectrometry.
AB  - The reconstruction of disturbed landscapes back to working ecosystems is an issue
      of increasing importance for the oil sand areas in Alberta, Canada. In this
      context, the fate of oil-sand-derived organic material in the tailings sands used
      for reclamation is of utmost environmental importance. Here we use electrospray
      ionization Fourier transform ion cyclotron resonance mass spectrometry of maltene
      fractions to identify compositional variations over a complete oil sand mining
      and recultivation process chain. On the basis of bulk compound class
      distributions and percentages of unique elemental compositions, we identify
      specific compositional features that are related to the different steps of the
      process chain. The double bond equivalent and carbon number distributions of the
      N1 and S1O2 classes are almost invariant along the process chain, despite a
      significant decrease in overall abundance. We thus suggest that these oil-sand
      derived components can be used as sensitive tracers of residual bitumen, even in
      soils from relatively old reclamation sites. The patterns of the O2, O3, and O4
      classes may be applied to assess process-chain-related changes in organic matter
      composition, including the formation of plant-derived soil organic matter on the
      reclamation sites. The N1O2 species appear to be related to unidentified
      processes in the tailings ponds but do not represent products of aerobic
      biodegradation of pyrrolic nitrogen compounds. 

PMID- 25961671
TI  - Chemical profiling of the genome with anti-cancer drugs defines target
      specificities.
AB  - Many anticancer drugs induce DNA breaks to eliminate tumor cells. The
      anthracycline topoisomerase II inhibitors additionally cause histone eviction.
      Here, we performed genome-wide high-resolution mapping of chemotherapeutic
      effects of various topoisomerase I and II (TopoI and II) inhibitors and
      integrated this mapping with established maps of genomic or epigenomic features
      to show their activities in different genomic regions. The TopoI inhibitor
      topotecan and the TopoII inhibitor etoposide are similar in inducing DNA damage
      at transcriptionally active genomic regions. The anthracycline daunorubicin
      induces DNA breaks and evicts histones from active chromatin, thus quenching
      local DNA damage responses. Another anthracycline, aclarubicin, has a different
      genomic specificity and evicts histones from H3K27me3-marked heterochromatin,
      with consequences for diffuse large B-cell lymphoma cells with elevated levels of
      H3K27me3. Modifying anthracycline structures may yield compounds with selectivity
      for different genomic regions and activity for different tumor types. 

PMID- 25961673
TI  - Efficient removal of organic ligands from supported nanocrystals by fast thermal
      annealing enables catalytic studies on well-defined active phases.
AB  - A simple yet efficient method to remove organic ligands from supported
      nanocrystals is reported for activating uniform catalysts prepared by colloidal
      synthesis procedures. The method relies on a fast thermal treatment in which
      ligands are quickly removed in air, before sintering can cause changes in the
      size and shape of the supported nanocrystals. A short treatment at high
      temperatures is found to be sufficient for activating the systems for catalytic
      reactions. We show that this method is widely applicable to nanostructures of
      different sizes, shapes, and compositions. Being rapid and effective, this
      procedure allows the production of monodisperse heterogeneous catalysts for
      studying a variety of structure-activity relationships. We show here results on
      methane steam reforming, where the particle size controls the CO/CO2 ratio on
      alumina-supported Pd, demonstrating the potential applications of the method in
      catalysis. 

PMID- 25961674
TI  - Medical licensing examination (uigwa) and the world of the physician officers
      (uigwan) in Korea's Joseon Dynasty.
AB  - Physicians for ordinary people in Korea's Joseon Dynasty (1392-1910) did not need
      to pass the national medical licensing examination. They were able to work after
      a sufficient apprenticeship period. Only physician officers were licensed as
      technical civil servants. These physician officers were middle class, located
      socially between the nobility and the commoner. They had to pass a national
      licensing examination to be considered for high-ranking physician officer
      positions, that is, those at the rank equal to or above the 6th level out of a
      total of 9 ranks, where the first rank was highest. Royal physicians also had to
      pass this examination before accepting responsibility for the King's healthcare.
      This article aims to describe the world of physician officers during the Joseon
      Dynasty. Physician officers enjoyed considerable social status because they dealt
      with matters of life and death. Owing to the professional nature of their fields
      and a strong sense of group identity, they came to compose a distinct social
      class. The physician officers' world was marked by strong group allegiances based
      on shared professional knowledge; the use of marriage to gain and maintain social
      status; and the establishment of hereditary technical posts within the medical
      profession that were handed down from one generation to the next. The medical
      licensing examination persisted until 1894 when the civil service examination
      agency, of which it was part, was abolished. Until that time, the testing agency,
      the number of candidates who were accepted, two-step test procedures, and the
      method of test item selection were maintained and enforced. 

PMID- 25961675
TI  - Best-fit model of exploratory and confirmatory factor analysis of the 2010
      Medical Council of Canada Qualifying Examination Part I clinical decision-making
      cases.
AB  - PURPOSE: This study aims to assess the fit of a number of exploratory and
      confirmatory factor analysis models to the 2010 Medical Council of Canada
      Qualifying Examination Part I (MCCQE1) clinical decision-making (CDM) cases. The
      outcomes of this study have important implications for a range of domains,
      including scoring and test development. METHODS: The examinees included all first
      time Canadian medical graduates and international medical graduates who took the
      MCCQE1 in spring or fall 2010. The fit of one- to five-factor exploratory models
      was assessed for the item response matrix of the 2010 CDM cases. Five
      confirmatory factor analytic models were also examined with the same CDM response
      matrix. The structural equation modeling software program Mplus was used for all
      analyses. RESULTS: Out of the five exploratory factor analytic models that were
      evaluated, a three-factor model provided the best fit. Factor 1 loaded on three
      medicine cases, two obstetrics and gynecology cases, and two orthopedic surgery
      cases. Factor 2 corresponded to pediatrics, and the third factor loaded on
      psychiatry cases. Among the five confirmatory factor analysis models examined in
      this study, three- and four-factor lifespan period models and the five-factor
      discipline models provided the best fit. CONCLUSION: The results suggest that
      knowledge of broad disciplinary domains best account for performance on CDM
      cases. In test development, particular effort should be placed on developing CDM
      cases according to broad discipline and patient age domains; CDM testlets should
      be assembled largely using the criteria of discipline and age.

PMID- 25961676
TI  - The implementation of problem-based learning in collaborative groups in a
      chiropractic program in Malaysia.
AB  - PURPOSE: Problem-based learning (PBL) is usually conducted in small-group
      learning sessions with approximately eight students per facilitator. In this
      study, we implemented a modified version of PBL involving collaborative groups in
      an undergraduate chiropractic program and assessed its pedagogical effectiveness.
      METHODS: This study was conducted at the International Medical University, Kuala
      Lumpur, Malaysia, and involved the 2012 chiropractic student cohort. Six PBL
      cases were provided to chiropractic students, consisting of three PBL cases for
      which learning resources were provided and another three PBL cases for which
      learning resources were not provided. Group discussions were not continuously
      supervised, since only one facilitator was present. The students' perceptions of
      PBL in collaborative groups were assessed with a questionnaire that was divided
      into three domains: motivation, cognitive skills, and perceived pressure to work.
      RESULTS: Thirty of the 31 students (97%) participated in the study. PBL in
      collaborative groups was significantly associated with positive responses
      regarding students' motivation, cognitive skills, and perceived pressure to work
      (P<0.05). The students felt that PBL with learning resources increased motivation
      and cognitive skills (P<0.001). CONCLUSION: The new PBL implementation described
      in this study does not require additional instructors or any additional funding.
      When implemented in a classroom setting, it has pedagogical benefits equivalent
      to those of small-group sessions. Our findings also suggest that students rely
      significantly on available learning resources.

PMID- 25961677
TI  - Ribonuclease Activity of an Artificial Catalyst That Combines a Ligated Cu(II)
      Ion and a Guanidinium Group at the Upper Rim of a cone-Calix[4]arene Platform.
AB  - A cone-calix[4]arene derivative, featuring a guanidinium group and a Cu(II) ion
      ligated to a 1,4,7-triazacyclononane (TACN) ligand at the 1,3-distal positions of
      the upper rim, effectively catalyzes the cleavage of 2-hydroxypropyl p
      nitrophenyl phosphate (HPNP) and a number of diribonucleoside 3',5'
      monophosphates (NpN'). Kinetic and potentiometric measurements support the
      operation of a general-base/general-acid mechanism and demonstrate that the
      hydroxo form of the ligated Cu(II) ion is the sole catalytically active species.
      Rate enhancements relative to the background hydrolysis reaction at 1 mM catalyst
      concentration are 6 * 10(5)-fold for HPNP and cluster around 10(7)-fold with the
      most favorable catalyst-NpN' combinations. 

PMID- 25961678
TI  - Bacterial genetics: A CRISPR sense of self.

PMID- 25961679
TI  - Photoregulating RNA digestion using azobenzene linked dumbbell antisense
      oligodeoxynucleotides.
AB  - Introduction of 4,4'-bis(hydroxymethyl)-azobenzene (azo) to dumbbell hairpin
      oligonucleotides at the loop position was able to reversibly control the
      stability of the whole hairpin structure via UV or visible light irradiation.
      Here, we designed and synthesized a series of azobenzene linked dumbbell
      antisense oligodeoxynucleotides (asODNs) containing two terminal hairpins that
      are composed of an asODN and a short inhibitory sense strand. Thermal melting
      studies of these azobenzene linked dumbbell asODNs indicated that efficient trans
      to cis photoisomerization of azobenzene moieties induced large difference in
      thermal stability (DeltaTm = 12.1-21.3  degrees C). In addition, photomodulation
      of their RNA binding abilities and RNA digestion by RNase H was investigated. The
      trans-azobenzene linked asODNs with the optimized base pairs between asODN
      strands and inhibitory sense strands could only bind few percentage of the target
      RNA, while it was able to recover their binding to the target RNA and degrade it
      by RNase H after light irradiation. Upon optimization, it is promising to use
      these azobenzene linked asODNs for reversible spatial and temporal regulation of
      antisense activities based on both steric binding and RNA digestion by RNase H. 

PMID- 25961680
TI  - All-Graphene Three-Terminal-Junction Field-Effect Devices as Rectifiers and
      Inverters.
AB  - We present prominent tunable and switchable room-temperature rectification
      performed at 100 kHz ac input utilizing micrometer-scale three-terminal junction
      field-effect devices. Monolayer CVD graphene is used as both a channel and a gate
      electrode to achieve all-graphene thin-film structure. Instead of ballistic
      theory, we explain the rectification characteristics through an electric-field
      capacitive model based on self-gating in the high source-drain bias regime.
      Previously, nanoscale graphene three-terminal junctions with the ballistic (or
      quasi-ballistic) operation have shown rectifications with relatively low
      efficiency. Compared to strict nanoscale requirements of ballistic devices,
      diffusive operation gives more freedom in design and fabrication, which we have
      exploited in the cascading device architecture. This is a significant step for
      all-graphene thin-film devices for integrated monolithic graphene circuits. 

PMID- 25961681
TI  - Germanium Silicon Alloy Anode Material Capable of Tunable Overpotential by
      Nanoscale Si Segregation.
AB  - We developed the novel electrode that enables fine control of overpotential by
      exploiting surface segregation that is the enrichment of one component at the
      surface of binary alloy. To realize this approach, we controlled the proportion
      of Si with low Li diffusivity at the surface by annealing the SiGe nanowire in H2
      environment at various temperatures. The resulting SiGe nanowires annealed at 850
      degrees C exhibited high reversible capacity (>1031 mA.h.g(-1)), and long cycle
      life (400 cycles) with high capacity retention (89.0%) at 0.2 C. This superior
      battery performance is attributed to the remaining unlithiated part acting as
      support frame to prevent pulverization of anode material, which results from the
      fine-tuning of overpotential by controlling the degree of Si segregation. 

PMID- 25961682
TI  - Histamine H4 receptor: insights into a potential therapeutic target in breast
      cancer.
AB  - Breast cancer is the second most common cancer worldwide, and the leading cause
      of cancer death in women. Several studies underlined the critical role of
      histamine in breast cancer development and progression. This review addresses the
      latest evidence regarding the involvement of histamine and histamine receptors in
      breast cancer, focusing particularly in the histamine H4 receptor (H4R).
      Histamine concentration in breast cancer tissues was found to be higher than that
      in normal tissues of healthy controls by means of an increase in the activity of
      histidine decarboxylase (HDC), the enzyme involved in histamine production. The
      expression of H4R in different experimental models and human biopsies, the
      associated biological responses, as well as the in vivo treatment of experimental
      tumors with H4R ligands is reviewed. Evidence demonstrates that the H4R exhibits
      a key role in histamine-mediated biological processes such as cell proliferation,
      senescence and apoptosis in breast cancer. The polymorphisms of the H4R and HDC
      genes and their association with breast cancer risk and malignancy reinforce the
      critical (patho)physiological role of H4R in breast cancer. In addition, H4R
      agonists display anti-tumor effects in vivo in a triple negative breast cancer
      model. The findings support the exploitation of the H4R as a molecular target for
      breast cancer drug development. 

PMID- 25961683
TI  - Object recognition test for studying cognitive impairments in animal models of
      Alzheimer's disease.
AB  - Animal models are essential resources in basic research and drug discovery in the
      field of Alzheimer's disease (AD). As the main clinical feature in AD is
      cognitive failure, the ultimate readout for any interventions or the ultimate
      goal in research should be measures of learning and memory. Although there is a
      wealth of genetic and biochemical studies on proposed AD pathogenic pathways, the
      aetiology of the illness remains unsolved. Therefore, assessment by cognitive
      assays should target relevant memory systems without assumptions about
      pathogenesis. The description of several tests that are available for assessing
      cognitive functioning in animal models can be found in literature. Among the
      behavioural test, the novel object recognition (NOR) task is a method to measure
      a specific form of recognition memory. It is based on the spontaneous behaviour
      of rodents and offers the advantage of not needing external motivation, reward or
      punishment. Therefore, the NOR test has been increasingly used as an experimental
      tool in assessing drug effects on memory and investigating the neural mechanisms
      underlying learning and memory. This review describes the basic procedure,
      modifications, practical considerations, and the requirements and caveats of this
      behavioural paradigm to be considered as appropriate for the study of AD.
      Altogether, NOR test could be considered as a very useful instrument that allows
      researchers to explore the cognitive status of rodents, and hence, for studying
      AD related pathological mechanisms or treatments. 

PMID- 25961684
TI  - The role of nutritional lipids and antioxidants in UV-induced skin cancer.
AB  - Two dietary tenets of the free radical theory of cancer require refinement. The
      first was dietary reduction of vulnerable free-radical targets, e.g.,
      polyunsaturated lipids. The second was the addition of one or more antioxidants
      to the diet. Further, it was reported in 1939 that high levels of dietary fat
      exacerbated UV-carcinogenesis. Both lines of enquiry (dietary lipid and
      antioxidant effects on UV-carcinogenesis) were investigated. Both dietary lipids
      and antioxidants modified carcinogenic expression. Increasing levels of omega-6
      polyunsaturated fatty acids (PUFA) exacerbated UV-carcinogenesis. However, omega
      3 PUFA dramatically inhibited carcinogenic expression. It is probable that the
      action of omega-6 and-3 PUFA rests with differential metabolic intermediates,
      both tumor promoting and immune-modulating, that each PUFA generates through
      lipoxygenase and cyclooxygenase pathways. Antioxidant supplementation with
      butylated hydroxytoluene or beta-carotene demonstrated that each exerted its own
      specific antioxidant mechanism(s). When introduced into the complex milieu of the
      cell with its own intricate and complex antioxidant defense system, detrimental
      effects may ensue. These results point to oversimplification of these dietary
      suggestions to reduce cancer risk and the necessity to refine these dietary
      recommendations. 

PMID- 25961685
TI  - Effect of early endometriosis on ovarian reserve and reproductive outcome.
AB  - Accumulating evidence suggests that advanced (moderate/severe) endometriosis
      negatively affects female fecundity, whereas the influence of early
      (minimal/mild) endometriosis on human reproduction remains unclear. Recent
      studies showed that the presence of the early pelvic endometriosis lesions
      deteriorates the ovarian reserve, luteal function, and fertilization rate in
      infertile women undergoing in vitro fertilization-embryo transfer treatment, but
      not their final reproductive outcome. Meanwhile, laparoscopic resection of early
      endometriosis lesions may be a promising therapeutic option to improve the
      fecundity of the affected subfertile women. Insufficient evidence on the
      relationship between early endometriosis, ovarian reserve, and reproductive
      outcome warrants further investigations. 

PMID- 25961686
TI  - Epigenetic crosstalk: a molecular language in human metabolic disorders.
AB  - Technological breakthroughs are emphasizing the impact of epigenetic mechanisms
      in human health highlighting the importance of a fine-tune orchestration of DNA
      methylation, micro RNAs, histone modifications, and chromatin structure.
      Transcriptional regulators sense the concentration of intermediary metabolites
      associated to a wide variety of biological processes including the long-term
      imprinting and heritable DNA methylation. Recent epigenetic mechanisms associated
      with cholesterol and lipid homeostasis have a critical impact in the
      susceptibility, development and progression of complex diseases such as type 2
      diabetes mellitus, non-alcoholic fatty liver, obesity and metabolic syndrome. The
      heritability of epigenetic states emerge as an additional level of complexity
      where the extension of somatic as well as inherited epigenetic modifications may
      require a thoughtful reconsideration in many human diseases related with
      metabolic disorders. 

PMID- 25961688
TI  - Colorectal endometriosis and pregnancy wish: why doing primary surgery.
AB  - One of the most interesting debates surrounding deep endometriosis concerns the
      management of patients with colorectal lesions and pregnancy intention, for which
      no strong first level of evidence data exists to recommend performing surgical
      excision of colorectal endometriosis or ART. Studies assessing the policy of
      primary IVF have recorded pregnancy rates inferior to 45% and estimated
      cumulative pregnancy rates after up to 3 cycles or IVF as high as 68%. Other
      authors have reported pregnancy rates over 60% in patients undergoing primary
      surgery for colorectal endometriosis, with spontaneous conception representing up
      to 60% of pregnancies. Although overall pregnancy rates appear roughly comparable
      in patients undergoing either IVF followed by surgery or surgery followed if
      required by IVF, questions remain as to whether delaying surgery for months or
      years impairs health. Delaying surgery may lead to bowel occlusion, higher rates
      of radical colorectal procedures, increased postoperative morbidity and prolonged
      painful complaints. To provide definitive answers requires a randomized trial on
      an international scale with a sample size exceeding 400 patients and follow up
      averaging 4 years. 

PMID- 25961687
TI  - How fisetin reduces the impact of age and disease on CNS function.
AB  - It is becoming increasingly clear that neurological diseases are multi-factorial
      involving disruptions in multiple cellular systems. Thus, while each disease has
      its own initiating mechanisms and pathologies, certain common pathways appear to
      be involved in most, if not all, neurological diseases. Thus, it is unlikely that
      modulating only a single factor will be effective at either preventing disease
      development or slowing disease progression. A better approach is to identify
      small (< 900 daltons) molecules that have multiple biological activities relevant
      to the maintenance of brain function. We have identified an orally active, novel
      neuroprotective and cognition-enhancing molecule, the flavonoid fisetin. Fisetin
      not only has direct antioxidant activity but it can also increase the
      intracellular levels of glutathione, the major intracellular antioxidant. Fisetin
      can also activate key neurotrophic factor signaling pathways. In addition, it has
      anti-inflammatory activity and inhibits the activity of lipoxygenases, thereby
      reducing the production of pro-inflammatory eicosanoids and their by-products.
      This wide range of actions suggests that fisetin has the ability to reduce the
      impact of age-related neurological diseases on brain function.

PMID- 25961690
TI  - Endangered species: mitochondrial DNA loss as a mechanism of human disease.
AB  - Human mitochondrial DNA (mtDNA) is a small maternally inherited DNA, typically
      present in hundreds of copies in a single human cell. Thus, despite its small
      size, the mitochondrial genome plays a crucial role in the metabolic homeostasis
      of the cell. Our understanding of mtDNA genotype-phenotype relationships is
      derived largely from studies of the classical mitochondrial neuromuscular
      diseases, in which mutations of mtDNA lead to compromised mitochondrial
      bioenergetic function, with devastating pathological consequences. Emerging
      research suggests that loss, rather than mutation, of mtDNA plays a major role
      across a range of prevalent human diseases, including diabetes mellitus,
      cardiovascular disease, and aging. Here, we examine the 'rules' of mitochondrial
      genetics and function, the clinical settings in which loss of mtDNA is an
      emerging pathogenic mechanism, and explore mtDNA damage and its consequences for
      the organellar network and cell at large. As extranuclear genetic material
      arrayed throughout the cell to support metabolism, mtDNA is increasingly
      implicated in a host of disease conditions, opening a range of exciting questions
      regarding mtDNA and its role in cellular homeostasis.

PMID- 25961691
TI  - Historical perspective of matrix metalloproteases.
AB  - Matrix metalloproteinases (MMPs) were identified as early as 1962. Since this
      seminal finding, this family of zinc-dependent endopeptidases has been studied
      extensively. This collective work has resulted in delineation of MMP gene and
      protein structures, the mechanisms of control of MMPs, the action of MMPs on both
      extracellular matrices and other proteins such as growth factors and cytokines,
      naturally-occurring mechanisms of control, and of course their role in normal
      physiology and their crucial roles in pathophysiology. Stemming from the
      discovery that MMPs contribute to arthritis, heart disease, and cancer, amongst
      other diseases, attempts to develop treatment strategies incorporating MMP
      inhibition have been undertaken. The results of these endeavours have been
      mediocre, resulting in few FDA-approved MMP inhibitors mostly due to the broad
      spectrum nature of these early inhibitors and unwanted side effects of MMP
      inhibition. The future of exploitation of MMPs in disease lies in the design of
      more targeted inhibitors; in order to accomplish this, we must all understand the
      subtle differences between each MMP and their contextual roles. In this chapter,
      we aim to overview major topics regarding MMPs and what direction we may go in
      the future. 

PMID- 25961689
TI  - Roles of lncRNA in breast cancer.
AB  - Recent systematic genomic studies have revealed a broad spectrum of lncRNAs that
      are involved in a variety of disease (diseases), including tumor progression, by
      regulating gene expression at epigenetic, transcriptional and post
      transcriptional levels. However, their exact roles of physiological function and
      the mechanism (mechanisms) of action are yet to be clarified. In breast cancer
      research, several lncRNAs are identified as tumor driving oncogenic lncRNAs and
      few are identified as tumor suppressive lncRNAs. They are involved in cell
      growth, apoptosis, cell migration and invasiveness as well as cancer cell
      stemness. Therefore, this new class of RNAs may serve as biomarkers for
      diagnostic and prognostic purpose and also as potential therapeutic targets. This
      review summarizes the current information about lncRNAs that are particularly
      involved in breast cancer progression and also discusses the potential
      translational application of these newly discovered nucleic acids.

PMID- 25961692
TI  - Degradomics of matrix metalloproteinases in inflammatory diseases.
AB  - Organisms have evolved to react to stress, tissue damage and pathogen invasion to
      assure their survival. Leukocytes are the primary responders and they regulate
      repair, immune defense and inflammation with the aid of a wide variety of other
      cells (e.g. epithelial, fibroblasts). To assure proper responses, a plethora of
      proteins are involved including signaling molecules, chemokines and proteases to
      orchestrate a step-by-step reaction. Inflammation is an essential biological
      process, however, when it persists, it can lead to various diseases that are
      challenging to heal or cure. The technologies and techniques covered in this book
      chapter can be applied to study all proteases and their inhibitors although will
      be centered on the matrix metalloproteinases (MMPs). It will focus on the
      proteolysis performed by MMPs, their various beneficial and detrimental effects
      in inflammation and the novel methods to study their roles on human diseases. 

PMID- 25961693
TI  - Matrix metalloproteinase function in non-mammalian model organisms.
AB  - Matrix metalloproteinases (MMPs), adamalysins, astacins, and serralysins are
      members of the metzincin superfamily of proteases. MMPs constitute a large
      protein family of both secreted and membrane-tethered enzymes that are
      synthesized as zymogens (proMMP) and activated by a cysteine-switch mechanism.
      First described over 50 years ago by Gross and Lapiere as a collagenolytic
      activity in amphibian tissues, the human MMP family now encompasses 23 different
      genes whose encoded proteins are capable of cleaving a variety of extracellular
      matrix protein substrates. Since their expression is upregulated in many cancer
      cell types, MMPs have received much attention particularly in the areas of tumor
      progression and metastasis. However, in terms of normal developmental processes,
      much less is known regarding MMP function and substrate identity. Data from
      knockout mouse studies support the notion that MMPs are not essential regulators
      of embryonic development, suggesting redundancy between MMPs or the presence of
      subtle phenotypes. However, studies on MMP function in other model systems
      indicate a larger role for MMP-dependent proteolysis during embryonic processes.
      Here, we review the current knowledge of MMPs from diverse model systems ranging
      from flowering plants and invertebrates to non-mammalian vertebrates. 

PMID- 25961694
TI  - Drug repositioning in Alzheimer's disease.
AB  - Drug repositioning offers an innovative approach to drug discovery with great
      potential in the field of Alzheimer's Disease and dementia therapeutics.
      Investigation of licensed compounds enables processing through the drug discovery
      pipeline in a rapid and cost-effective manner. A growing body of evidence
      supports the translation of priority compounds to be taken forward to clinical
      trials, based on established and proposed mechanisms of action. A number of drugs
      have already entered clinical trial following repositioning, and novel
      technologies have been created to enable high-throughput screening. This review
      discusses the novel approaches that build on transcriptional signature profiling
      to support repositioning in AD, and the novel candidate drugs that are emerging
      from this exciting new technique. 

PMID- 25961695
TI  - Ageing, neuroinflammation and neurodegeneration.
AB  - During ageing, different iron complexes accumulate in specific brain regions
      which are associated with motor and cognitive dysfunction. In neurodegenerative
      diseases, such as Alzheimer's disease and Parkinson's disease, changes in local
      iron homoeostasis result in altered cellular iron distribution and accumulation,
      ultimately inducing neurotoxicity. The use of iron chelators which are able to
      penetrate the blood brain barrier and reduce excessive iron accumulation in
      specific brain regions have been shown to reduce disease progression in both
      Parkinson's disease and Friedreich's Ataxia. Neuroinflammation often occurs in
      neurodegenerative diseases, which is mainly sustained by activated microglia
      exhibiting the M1 phenotype. Such inflammation contributes to the disease
      progression. Therapeutic agents which reduce such inflammation, e.g. taurine
      compounds, may ameliorate the inflammatory process by switching the microglia
      from a M1 to a M2 phenotype. 

PMID- 25961696
TI  - Prognostic factors in paediatric anaplastic large cell lymphoma: role of ALK.
AB  - Event-free survival of children and adolescents with ALK-positive anaplastic
      large cell lymphoma (ALCL) reaches 65-75% with current chemotherapy regimen. Risk
      stratification of children with ALCL was, until now, based on clinical
      parameters. More recently, pathological and biological risk factors have been
      described in trials applying BFM-type chemotherapy. Histological subtypes
      containing small-cell or lymphohistiocytic components indicate a high risk of
      failure. Minimal disseminated disease (MDD) detected by qualitative RT-PCR for
      NPM-ALK in bone marrow or blood is associated with a relapse risk of 50%.
      Quantification of MDD and persistent minimal residual disease (MRD) characterize
      very high risk patients. Serum ALK-autoantibody titres inversely correlate with
      relapse risk. The combination of MDD and ALK-antibody titre separates both low
      and very high risk patients from those with standard risk. In relapse, the time
      of relapse/progression, central nervous system and bone marrow involvement are
      major risk factors. In conclusion, MDD, MRD, ALK-antibody titres and histological
      subtype are strong biological risk factors in childhood ALCL. The combination of
      MDD and ALK-antibody titre may serve for patient stratification in upcoming
      clinical trials. 

PMID- 25961697
TI  - MicroRNA and ALK-positive anaplastic large cell lymphoma.
AB  - In this review we describe the current literature covering the role of microRNA
      in anaplastic large cell lymphoma (ALCL). MicroRNA is one of the best
      characterized subgroups of non-coding RNAs and it is now becoming clear that its
      importance in oncogenesis has been greatly underestimated. In ALCL the
      deregulation of a diverse range of microRNA has been demonstrated however much
      less is known about the physiological consequences of this deregulation. Here we
      focus on the subgroup of ALCL bearing the anaplastic lymphoma kinase (ALK)
      translocation (ALK+). The pathways linking oncogenic ALK signaling and the
      regulation of microRNA are now becoming established with the transcription factor
      STAT3 appearing to play an important role in the epigenetic regulation. This
      review will discuss our current understanding of the role of microRNAs in ALK
      mediated oncogenesis and will explain why we believe these new findings suggest
      that the use of methyltransferase inhibitors together with microRNA-specific
      drugs could be a useful addition to our current armamentarium in the fight
      against ALK(+) ALCL. 

PMID- 25961698
TI  - The role of AP-1 and epigenetics in ALCL.
AB  - Anaplastic large cell lymphoma (ALCL) is an aggressive, highly proliferative, T
      cell lymphoma with increasing incidence worldwide. Anaplastic Lymphoma Kinase
      (ALK) fusions occur in about 50% of all cases. Most ALK positive cases of ALCL
      harbor the t(2;5) translocation that leads to expression of Nucleophosmin
      Anaplastic Lymphoma Kinase (NPM-ALK). NPM-ALK induces a variety of oncogenic
      signaling pathways that lead to malignant transformation of T-cells via Activator
      Protein-1 (AP-1), STAT3 and other (transcription) factors. In addition to the
      commonly known AP-1 activators Mitogen-Activated Protein Kinases (MAPKs), there
      are other signaling pathways, such as PI3K/mTOR/AKT, which are implicated in AP-1
      activation/expression in ALCL. The AP-1 factor JUNB was shown to drive ALCL
      proliferation and the expression of the characteristic ALCL Ki-1 antigen, CD30.
      cJUN and JUNB target PDGFRB, thereby leading to tumor progression and
      dissemination. Furthermore, aberrant gene expression in ALCL is frequently
      accompanied by changes in epigenetic regulatory mechanisms, such as DNA
      methylation patterns. Here, we discuss the role of AP-1 in the pathogenesis of
      ALCL and provide an overview of pathological epigenetic changes in ALCL cells. 

PMID- 25961699
TI  - Twenty years of modelling NPM-ALK-induced lymphomagenesis.
AB  - Our current understanding of oncogenic Anaplastic Lymphoma Kinase (ALK)-induced
      lymphomagenesis has relied for over 20 years on multiple and complementary
      studies performed on various experimental models, encompassing ALK oncogene
      expressing cells, their grafts into immune-compromised mice, the generation of
      genetically engineered mouse models (GEMMs) and, when available, the use of
      patient samples from Anaplastic Large Cell Lymphoma (ALCL) tumour banks. Of note,
      and to our knowledge, no ALK-positive ALCL 3D culture system has been described
      so far. In this review, we will first outline how these different cell and mouse
      models were designed, and what key findings they revealed (or confirmed) towards
      oncogenic ALK-induced lymphomagenesis. Secondly, we will discuss how recent and
      revolutionary advances in genetic engineering technology are likely to complete
      our understanding of ALK-related disease in an effort to improve current
      therapeutic approaches. 

PMID- 25961701
TI  - The origins of ALK translocations.
AB  - Translocations involving the anaplastic lymphoma kinase (ALK) gene locus on
      chromosome 2p23 were first described in anaplastic large cell lymphoma (ALCL).
      Although most commonly fused to the nucleophosmin (NPM1) gene on chromosome 5q35,
      which results in the t(2;5)(p23;q35)/NPM1-ALK translocation, several other ALK
      translocation partners have meanwhile been identified. Furthermore, apart from
      ALCL, ALK-involving translocations have been described in other hematopoietic and
      non-hematopoietic cancers. However, despite a rapid increase in literature on the
      nature and tissue distribution of ALK-translocations, much less is known about
      the mechanisms of formation of these translocations. The emergence of
      translocations has been linked to the transcriptional activity of the respective
      genome regions, reorganization of the chromatin and activation of the DNA repair
      machinery. In this review we discuss mechanisms and implications of formation of
      ALK-translocations. 

PMID- 25961700
TI  - ALK-positive anaplastic large cell lymphoma: an evolving story.
AB  - The current classification of lymphoid neoplasms is based on the integrated
      utilisation of morphological, immunohistochemical, genetic and clinical criteria
      to define disease entities. Anaplastic large cell lymphoma is a paradigm for the
      identification of a disease entity based on morphological observations and
      immunophenotype, which paved the way for the subsequent discovery of the
      characteristic cytogenetic abnormality the translocation t(2;5)(p23;q35). In
      1994, the t(2;5) was cloned and the NPM-ALK fusion gene generated by this
      rearrangement was identified. The year 2014 marked the 20th anniversary of this
      seminal publication by Steve Morris et al. The discovery of anaplastic lymphoma
      kinase (ALK) has allowed the definition of a distinct entity within the
      clinically and pathologically heterogeneous group of CD30+ lymphomas. The
      diagnosis of ALK-positive ALCL has become straightforward due to the generation
      of the reliable monoclonal antibody ALK-1 that also has led to the recognition of
      the histologic spectrum of the disease. ALK-positive ALCL has evolved in the last
      20 years to an exciting model for signal transduction studies and targeted
      therapy.

PMID- 25961703
TI  - Anaplastic lymphoma kinase: activating mechanisms and signaling pathways.
AB  - The discovery of Anaplastic Lymphoma Kinase (ALK) by Stephan Morris and
      colleagues twenty years ago has led to an unprecedented opportunity and provided
      the basis for a novel and clinically powerful stratification of human cancers.
      The molecular and biological characterization of ALK and the recognition of
      alternative mechanisms of activation of the tyrosine kinase receptors have then
      set the basis for the development and the subsequent application of selective
      small molecules. These achievements have fostered a new era in oncology, and the
      result of this new avenue has drastically changed the expectation of many cancer
      patients. Here we review the mechanisms of ALK activation and the modalities that
      drive ALK pathogenesis. 

PMID- 25961702
TI  - The anaplastic lymphoma kinase as an oncogene in solid tumors.
AB  - Twenty years ago anaplastic lymphoma kinase (ALK) was discovered in anaplastic
      large cell lymphoma (ALCL), but the interest in ALK as an oncogene grew only in
      recent years when ALK rearrangements were reported as recurrent genetic lesions
      in lung carcinoma and activating single point mutations were described in
      neuroblastoma. In this review we will describe the main features of ALK
      rearranged solid tumors, with particular emphasis to NSCLC and neuroblastoma. We
      will discuss the numerous in vitro and in vivo studies that confirmed ALK as the
      driver oncogene in these tumors and the achievements in clinical settings with
      ALK inhibitors that validated ALK as a therapeutic target. We will finally end
      with the description of putative innovative therapeutic approaches that are on
      going to overcome acquired resistance that invariably occurs in crizotinib
      treated NSCLC patients or intrinsic resistance to crizotinb therapy reported in
      neuroblastoma. 

PMID- 25961706
TI  - High Aspect-Ratio Iridium-Coated Nanopillars for Highly Reproducible Surface
      Enhanced Raman Scattering (SERS).
AB  - A variety of different gold and silver nanostructures have been proposed over the
      years as high sensitivity surface-enhanced Raman scattering (SERS) sensors.
      However, efficient use of SERS has been hindered by the difficulty of realizing
      SERS substrates that provide reproducible SERS response over the whole active
      area. Here, we show that atomic layer deposition (ALD) grown iridium can be used
      to produce highly reliable SERS substrates. The substrates are based on a
      periodic array of high aspect-ratio iridium coated nanopillars that feature
      efficient and symmetrically distributed hot spots within the interpillar gaps
      (gap width<10 nm). We show that the enhancement with the iridium based
      nanostructures is of significant magnitude and it equals the enhancement of
      silver based reference substrates. Most notably, we demonstrate that the ordered
      and well-defined plasmonic nanopillars offer a measurement-to-measurement
      variability of 5%, which paves the way for truly quantitative SERS measurements.

PMID- 25961707
TI  - Stabilization of Human Serum Albumin against Urea Denaturation by Diazepam and
      Ketoprofen.
AB  - Stabilizing effect of diazepam and ketoprofen, Sudlow's site II markers on human
      serum albumin (HSA) against urea denaturation was studied using fluorescence
      spectroscopy. The two-step, three-state urea transition of HSA was transformed
      into a single-step, two-state transition with the abolishment of the intermediate
      state along with a shift of the transition curve towards higher urea
      concentrations in the presence of diazepam or ketoprofen. Interestingly, a
      greater shift in the transition curve of HSA was observed in the presence of
      ketoprofen compared to diazepam. A comparison of the intrinsic fluorescence and
      three-dimensional fluorescence spectra of HSA and partially-denatured HSAs,
      obtained in the absence and the presence of diazepam or ketoprofen suggested
      significant retention of native-like conformation in the partially-denatured
      states of HSA in the presence of Sudlow's site II markers. Taken together, all
      these results suggested stabilization of HSA in the presence of diazepam or
      ketoprofen, being greater in the presence of ketoprofen. 

PMID- 25961708
TI  - Structural Modelling, Substrate Binding and Stability Studies of Endopectate
      Lyase (PL1B) of Family 1 Polysaccharide Lyase from Clostridium thermocellum.
AB  - An endo-pectate lyase (PL1B) of family 1 polysaccharide lyase from Clostridium
      thermocellum was structurally characterized and its stability under chaotropic
      agent was determined. The putative domain PL1B was identified from the protein
      sequence ABN53381.1 belonging to superfamily 3 of pectate lyase. Multiple
      sequence alignment of PL1B with other known pectate lyases revealed the conserved
      and semi-conserved residues. The secondary structure of PL1B predicted by PsiPred
      and confirmed by Circular Dichroism showed the presence of 2 alpha-helices
      (2.06%), 26 beta-strands (40.54%) and 29 random coils (57.4%). The modelled
      protein represented right handed parallel beta-helix structure, where three
      parallel beta-sheets linked by loops coils around to form the beta-helix core.
      Quality assessment of energy minimized structure by Ramachandran plot displayed
      82.8% residues in favoured region. Superposition of PL1B structure with Bsp165
      PelA from Bacillus sp. revealed the substrate binding cleft formed by the amino
      acid residues from the loops and beta-sheet. Molecular dynamic simulation of
      modelled PL1B structure inferred that it is quite stable and compact. Docking
      studies identified Asp151, Arg209, Asn234, Arg236, Tyr271 and Ser272 as the key
      residues of PL1B involved during catalysis. Among them Arg209 is responsible for
      proton abstraction during beta-elimination. Protein melting studies on PL1B
      showed that there was 12 degrees C shift of peak from 74 to 86 degrees C in
      presence of 0.6 mM Ca(2+) ions, showing that they provide stability to the
      structure. The unfolding of PL1B by GuHCl or Urea by fluorescence study showed
      that the protein structure is stable and disintegrates at their higher
      concentrations. 

PMID- 25961710
TI  - Correction: Oxidative stress induced inflammation initiates functional decline of
      tear production.

PMID- 25961709
TI  - Atypical Role for PhoU in Mutagenic Break Repair under Stress in Escherichia
      coli.
AB  - Mechanisms of mutagenesis activated by stress responses drive pathogen/host
      adaptation, antibiotic and anti-fungal-drug resistance, and perhaps much of
      evolution generally. In Escherichia coli, repair of double-strand breaks (DSBs)
      by homologous recombination is high fidelity in unstressed cells, but switches to
      a mutagenic mode using error-prone DNA polymerases when the both the SOS and
      general (sigmaS) stress responses are activated. Additionally, the sigmaE
      response promotes spontaneous DNA breakage that leads to mutagenic break repair
      (MBR). We identified the regulatory protein PhoU in a genetic screen for
      functions required for MBR. PhoU negatively regulates the phosphate-transport and
      utilization (Pho) regulon when phosphate is in excess, including the PstB and
      PstC subunits of the phosphate-specific ABC transporter PstSCAB. Here, we
      characterize the PhoU mutation-promoting role. First, some mutations that affect
      phosphate transport and Pho transcriptional regulation decrease mutagenesis.
      Second, the mutagenesis and regulon-expression phenotypes do not correspond,
      revealing an apparent new function(s) for PhoU. Third, the PhoU mutagenic role is
      not via activation of the sigmaS, SOS or sigmaE responses, because mutations (or
      DSBs) that restore mutagenesis to cells defective in these stress responses do
      not restore mutagenesis to phoU cells. Fourth, the mutagenesis defect in phoU
      mutant cells is partially restored by deletion of arcA, a gene normally repressed
      by PhoU, implying that a gene(s) repressed by ArcA promotes mutagenic break
      repair. The data show a new role for PhoU in regulation, and a new regulatory
      branch of the stress-response signaling web that activates mutagenic break repair
      in E. coli. 

PMID- 25961711
TI  - Non-Invasive Acoustical sensing of Drug-Induced Effects on the Contractile
      Machinery of Human Cardiomyocyte Clusters.
AB  - There is an urgent need for improved models for cardiotoxicity testing. Here we
      propose acoustic sensing applied to beating human cardiomyocyte clusters for non
      invasive, surrogate measuring of the QT interval and other characteristics of the
      contractile machinery. In experiments with the acoustic method quartz crystal
      microbalance with dissipation monitoring (QCM-D), the shape of the recorded
      signals was very similar to the extracellular field potential detected in
      electrochemical experiments, and the expected changes of the QT interval in
      response to addition of conventional drugs (E-4031 or nifedipine) were observed.
      Additionally, changes in the dissipation signal upon addition of cytochalasin D
      were in good agreement with the known, corresponding shortening of the
      contraction-relaxation time. These findings suggest that QCM-D has great
      potential as a tool for cardiotoxicological screening, where effects of compounds
      on the cardiomyocyte contractile machinery can be detected independently of
      whether the extracellular field potential is altered or not. 

PMID- 25961713
TI  - Changes in the dynamics of foliar N metabolites in oak saplings by drought and
      air warming depend on species and soil type.
AB  - Climate change poses direct or indirect influences on physiological mechanisms in
      plants. In particular, long living plants like trees have to cope with the
      predicted climate changes (i.e. drought and air warming) during their life span.
      The present study aimed to quantify the consequences of simulated climate change
      for foliar N metabolites over a drought-rewetting-drought course. Saplings of
      three Central European oak species (i.e. Quercus robur, Q. petraea, Q. pubescens)
      were tested on two different soil types (i.e. acidic and calcareous). Consecutive
      drought periods increased foliar amino acid-N and soluble protein-N
      concentrations at the expense of structural N in all three oak species. In
      addition, transient effects on foliar metabolite dynamics were observed over the
      drought-rewetting-drought course. The lowest levels of foliar soluble protein-N,
      amino acid-N and potassium cation with a minor response to drought and air
      warming were found in the oak species originating from the driest/warmest habitat
      (Q. pubescens) compared to Q. robur and Q. petraea. Higher foliar osmolyte-N and
      potassium under drought and air warming were observed in all oak species when
      grown on calcareous versus acidic soil. These results indicate that species
      specific differences in physiological mechanisms to compensate drought and
      elevated temperature are modified by soil acidity. 

PMID- 25961714
TI  - THE MULTIDIMENSIONAL HEALTH LOCUS OF CONTROL SCALE: PSYCHOMETRIC PROPERTIES AND
      FORM EQUIVALENCE.
AB  - This study examined the psychometric equivalence of Forms A and B of the
      Multidimensional Health Locus of Control Scale in a sample of college students (N
      = 370; M = 19.5 yr.; 318 Caucasians; 281 women). Given the dearth of studies that
      address the issue of form equivalence directly, this study sought to ascertain
      whether these forms could be used interchangeably by researchers. Subscales on
      the two forms had fairly high correlations (range of r = .77-.81), and similar
      alpha and omega reliability coefficients. Additionally, confirmatory factor
      analysis revealed both forms fit a three-factor model well. However, paired
      sample t tests yielded significant mean differences for all three subscales.
      Furthermore, the two forms yielded inconsistent associations with relevant
      measures. Although the observed pattern of associations with social desirability
      and safe swimming behaviors were similar for Forms A and B, the pattern of
      differences was not identical for smoking groups and bicycle helmet use groups
      between forms. Overall, these results suggested that Forms A and B do not meet
      the strict criteria for parallel forms, but instead should be considered
      alternative forms.

PMID- 25961712
TI  - Accounting for Dynamic Fluctuations across Time when Examining fMRI Test-Retest
      Reliability: Analysis of a Reward Paradigm in the EMBARC Study.
AB  - Longitudinal investigation of the neural correlates of reward processing in
      depression may represent an important step in defining effective biomarkers for
      antidepressant treatment outcome prediction, but the reliability of reward
      related activation is not well understood. Thirty-seven healthy control
      participants were scanned using fMRI while performing a reward-related guessing
      task on two occasions, approximately one week apart. Two main contrasts were
      examined: right ventral striatum (VS) activation fMRI BOLD signal related to
      signed prediction errors (PE) and reward expectancy (RE). We also examined
      bilateral visual cortex activation coupled to outcome anticipation. Significant
      VS PE-related activity was observed at the first testing session, but at the
      second testing session, VS PE-related activation was significantly reduced.
      Conversely, significant VS RE-related activity was observed at time 2 but not
      time 1. Increases in VS RE-related activity from time 1 to time 2 were
      significantly associated with decreases in VS PE-related activity from time 1 to
      time 2 across participants. Intraclass correlations (ICCs) in VS were very low.
      By contrast, visual cortex activation had much larger ICCs, particularly in
      individuals with high quality data. Dynamic changes in brain activation are
      widely predicted, and failure to account for these changes could lead to
      inaccurate evaluations of the reliability of functional MRI signals. Conventional
      measures of reliability cannot distinguish between changes specified by
      algorithmic models of neural function and noisy signal. Here, we provide evidence
      for the former possibility: reward-related VS activations follow the pattern
      predicted by temporal difference models of reward learning but have low ICCs. 

PMID- 25961715
TI  - Online multi-modal robust non-negative dictionary learning for visual tracking.
AB  - Dictionary learning is a method of acquiring a collection of atoms for subsequent
      signal representation. Due to its excellent representation ability, dictionary
      learning has been widely applied in multimedia and computer vision. However,
      conventional dictionary learning algorithms fail to deal with multi-modal
      datasets. In this paper, we propose an online multi-modal robust non-negative
      dictionary learning (OMRNDL) algorithm to overcome this deficiency. Notably,
      OMRNDL casts visual tracking as a dictionary learning problem under the particle
      filter framework and captures the intrinsic knowledge about the target from
      multiple visual modalities, e.g., pixel intensity and texture information. To
      this end, OMRNDL adaptively learns an individual dictionary, i.e., template, for
      each modality from available frames, and then represents new particles over all
      the learned dictionaries by minimizing the fitting loss of data based on M
      estimation. The resultant representation coefficient can be viewed as the common
      semantic representation of particles across multiple modalities, and can be
      utilized to track the target. OMRNDL incrementally learns the dictionary and the
      coefficient of each particle by using multiplicative update rules to respectively
      guarantee their non-negativity constraints. Experimental results on a popular
      challenging video benchmark validate the effectiveness of OMRNDL for visual
      tracking in both quantity and quality. 

PMID- 25961716
TI  - Dendritic-tumor fusion cells derived heat shock protein70-peptide complex has
      enhanced immunogenicity.
AB  - Tumor-derived heat shock protein70-peptide complexes (HSP70.PC-Tu) have shown
      great promise in tumor immunotherapy due to numerous advantages. However, large
      scale phase III clinical trials showed that the limited immunogenicity remained
      to be enhanced. In previous research, we demonstrated that heat shock protein 70
      peptide complexes (HSP70.PC-Fc) derived from dendritic cell (DC)-tumor fusions
      exhibit enhanced immunogenicity compared with HSP70.PCs from tumor cells.
      However, the DCs used in our previous research were obtained from healthy donors
      and not from the patient population. In order to promote the clinical application
      of these complexes, HSP70.PC-Fc was prepared from patient-derived DC fused
      directly with patient-derived tumor cells in the current study. Our results
      showed that compared with HSP70.PC-Tu, HSP70.PC-Fc elicited much more powerful
      immune responses against the tumor from which the HSP70 was derived, including
      enhanced T cell activation, and CTL responses that were shown to be antigen
      specific and HLA restricted. Our results further indicated that the enhanced
      immunogenicity is related to the activation of CD4+ T cells and increased
      association with other heat shock proteins, such as HSP90. Therefore, the current
      study confirms the enhanced immunogenicity of HSP70.PC derived from DC-tumor
      fusions and may provide direct evidence promoting their future clinical use. 

PMID- 25961717
TI  - A Potential Solution to the Shortage of Solid Organs for Transplantation.

PMID- 25961718
TI  - Resveratrol-Induced Vascular Progenitor Differentiation towards Endothelial
      Lineage via MiR-21/Akt/beta-Catenin Is Protective in Vessel Graft Models.
AB  - BACKGROUND AND PURPOSE: Vessel graft failure is typically associated with
      arteriosclerosis, in which endothelial dysfunction/damage is a key event.
      Resveratrol has been shown to possess cardioprotective capacity and to reduce
      atherosclerosis. We aimed to study the influence of resveratrol on the behavior
      of resident stem cells that may contribute to graft arteriosclerosis.
      EXPERIMENTAL APPROACH: Vascular resident progenitor cells and embryonic stem
      cells were treated with resveratrol under differentiating conditions and
      endothelial markers expression was evaluated. Expression of miR-21 and beta
      catenin was also tested and exogenously modified. Effects of resveratrol
      treatment in an ex vivo re-endothelialization model and on mice undergone
      vascular graft were evaluated. KEY RESULTS: Resveratrol induced expression of
      endothelial markers such as CD31, VE-cadherin and eNOS in both progenitor and
      stem cells. We demonstrated that resveratrol significantly reduced miR-21
      expression, which in turn reduced Akt phosphorylation. This signal cascade
      diminished the amount of nuclear beta-catenin, inducing endothelial marker
      expression and increasing tube-like formation by progenitor cells. Both the
      inhibition of miR-21 and the knockdown of beta-catenin were able to recapitulate
      the effect of resveratrol application. Ex vivo, progenitor cells treated with
      resveratrol produced better endothelialization of the decellularized vessel.
      Finally, in a mouse model of vessel graft, a resveratrol-enhanced diet was able
      to reduce lesion formation. CONCLUSIONS AND IMPLICATIONS: We provide the first
      evidence that oral administration of resveratrol can reduce neointimal formation
      in a model of vascular graft and elucidated the underpinning miR-21/Akt/beta
      catenin dependent mechanism. These findings may support the beneficial effect of
      resveratrol supplementation for graft failure prevention.

PMID- 25961719
TI  - A doubling of microphytobenthos biomass coincides with a tenfold increase in
      denitrifier and total bacterial abundances in intertidal sediments of a temperate
      estuary.
AB  - Surface sediments are important systems for the removal of anthropogenically
      derived inorganic nitrogen in estuaries. They are often characterized by the
      presence of a microphytobenthos (MPB) biofilm, which can impact bacterial
      communities in underlying sediments for example by secretion of extracellular
      polymeric substances (EPS) and competition for nutrients (including nitrogen).
      Pyrosequencing and qPCR was performed on two intertidal surface sediments of the
      Westerschelde estuary characterized by a two-fold difference in MPB biomass but
      no difference in MPB composition. Doubling of MPB biomass was accompanied by a
      disproportionately (ten-fold) increase in total bacterial abundances while,
      unexpectedly, no difference in general community structure was observed, despite
      significantly lower bacterial richness and distinct community membership, mostly
      for non-abundant taxa. Denitrifier abundances corresponded likewise while
      community structure, both for nirS and nirK denitrifiers, remained unchanged,
      suggesting that competition with diatoms for nitrate is negligible at
      concentrations in the investigated sediments (appr. 1 mg/l NO3-). This study
      indicates that MPB biomass increase has a general, significantly positive effect
      on total bacterial and denitrifier abundances, with stimulation or inhibition of
      specific bacterial groups that however do not result in a re-structured
      community. 

PMID- 25961720
TI  - A systematic review of the amount of water per person per day needed to prevent
      morbidity and mortality in (post-)disaster settings.
AB  - BACKGROUND: In order to improve the effectiveness and efficiency of humanitarian
      efforts, minimum standards for humanitarian assistance and key indicators,
      showing whether a standard has been attained, have been developed. However, many
      of these standards and indicators are based on a consensus on best practices and
      experiences in humanitarian response, because relevant evidence on the impact of
      humanitarian interventions is often lacking. OBJECTIVES: One important example of
      a standard in humanitarian aid in a disaster setting is "water quantity." The
      accompanying indicator states how many litres of water are needed per person per
      day in a disaster setting. It was our objective to determine the evidence base
      behind this indicator, in order to improve health outcomes such as morbidity
      (e.g., diarrhoea) and mortality. METHODS: A systematic review was performed
      searching The Cochrane Library, Medline and Embase. We included studies performed
      during disasters and in refugee camps that reported a specific water amount and
      health-related outcomes related to water shortages, including diarrhoea, cholera,
      and mortality. We used GRADE to determine the quality of evidence. RESULTS: Out
      of 3,630 articles, 111 references relevant to our question were selected. Based
      on our selection criteria, we finally retained 6 observational studies, including
      1 study that was performed during the disaster and 5 studies in a post-disaster
      phase. From two studies there is conclusive evidence on the relationship between
      the amount of water received and diarrhoea or mortality rates in refugee camps.
      However, overall, these studies do not contain enough data with relevance to a
      specific amount of water, and the level of evidence is very low. CONCLUSIONS:
      More primary research on water amounts in a disaster setting is necessary, so
      that the humanitarian sector can further professionalise its water-related
      standards, indicators and interventions.

PMID- 25961721
TI  - Burden of HIV and Syphilis: A Comparative Evaluation between Male Sex Workers and
      Non-Sex-Worker Men Who Have Sex with Men in Urban China.
AB  - BACKGROUND: The increasing burden of sexually transmitted infections (STIs)
      including HIV and syphilis among male sex workers (MSWs) is a major global
      concern. The aim of our study was to evaluate the difference between MSWs and non
      commercial MSMs in China. METHODS: During 2008-09, in a cross-sectional study,
      2618 adult MSM were recruited through respondent-driven and snowball sampling
      from seven cities of China. Information regarding socio-demographics, risk
      behaviors, HIV-related knowledge and STI-related symptoms were collected and
      participants were tested for HIV and syphilis. RESULTS: Among 2618 participating
      MSM, 9.97% sold sex to males. HIV prevalence was 7.45% (6.13% among MSWs and
      7.59% among non-MSW MSM) and syphilis prevalence was 14.32% (10.73% for MSWs and
      14.72% for non-MSW MSM). Compared to non-MSW MSM, MSWs were more likely to be
      younger (adjusted odds ratio: aOR = 0.91, 95% confidence interval: 95%CI=0.88
      0.93), never married (aOR = 4.38, 95% CI = 2.38-6.80), less educated,
      heterosexual (aOR = 13.04, 95% CI = 6.08-27.95), less knowledgeable regarding HIV
      (aOR = 0.70, 95% CI=0.51-0.96), experiencing symptoms of STI (aOR = 2.16, 95% CI
      = 1.47-3.19), engaging in condomless vaginal intercourse (aOR = 2.16, 95% CI =
      1.47-3.19) and less likely to engage in condomless anal intercourse (aOR = 0.62,
      95% CI = 0.46-0.85). CONCLUSIONS: High HIV and syphilis prevalence warranted
      urgent intervention targeting MSWs as a separate sentinel group for efficient
      surveillance owing to their different distribution from non-MSW MSM. Although
      male sex workers and non-commercial homosexuals have similar rates of HIV and
      syphilis, MSWs have different characteristics which should be considered in
      designing intervention programs targeting them.

PMID- 25961722
TI  - Terfestatins B and C, New p-Terphenyl Glycosides Produced by Streptomyces sp. RM
      5-8.
AB  - Terfestatins B (1) and C (2), new p-terphenyls bearing a novel unsaturated
      hexuronic acid (4-deoxy-alpha-L-threo-hex-4-enopyranuronate), a unique beta-D
      glycosyl ester of 5-isoprenylindole-3-carboxylate (3) and the same rare sugar,
      and two new hygromycin precursors, were characterized as metabolites of the coal
      mine fire isolate Streptomyces sp. RM-5-8. EtOH damage neuroprotection assays
      using rat hippocampal-derived primary cell cultures with 1, 2, 3 and echoside B
      (a terfestatin C-3'-beta-D-glucuronide from Streptomyces sp. RM-5-8) revealed 1
      as potently neuroprotective, highlighting a new potential application of the
      terfestatin scaffold.

PMID- 25961723
TI  - Severe Adverse Maternal Outcomes among Women in Midwife-Led versus Obstetrician
      Led Care at the Onset of Labour in the Netherlands: A Nationwide Cohort Study.
AB  - OBJECTIVE: To test the hypothesis that it is possible to select a group of low
      risk women who can start labour in midwife-led care without having increased
      rates of severe adverse maternal outcomes compared to women who start labour in
      secondary care. DESIGN AND METHODS: We conducted a nationwide cohort study in the
      Netherlands, using data from 223 739 women with a singleton pregnancy between 37
      and 42 weeks gestation without a previous caesarean section, with spontaneous
      onset of labour and a child in cephalic presentation. Information on all cases of
      severe acute maternal morbidity collected by the national study into ethnic
      determinants of maternal morbidity in the Netherlands (LEMMoN study), 1 August
      2004 to 1 August 2006, was merged with data from the Netherlands Perinatal
      Registry of all births occurring during the same period. Our primary outcome was
      severe acute maternal morbidity (SAMM, i.e. admission to an intensive care unit,
      uterine rupture, eclampsia or severe HELLP, major obstetric haemorrhage, and
      other serious events). Secondary outcomes were postpartum haemorrhage and manual
      removal of placenta. RESULTS: Nulliparous and parous women who started labour in
      midwife-led care had lower rates of SAMM, postpartum haemorrhage and manual
      removal of placenta compared to women who started labour in secondary care. For
      SAMM the adjusted odds ratio's and 95% confidence intervals were for nulliparous
      women: 0.57 (0.45 to 0.71) and for parous women 0.47 (0.36 to 0.62). CONCLUSIONS:
      Our results suggest that it is possible to identify a group of women at low risk
      of obstetric complications who may benefit from midwife-led care. Women can be
      reassured that we found no evidence that midwife-led care at the onset of labour
      is unsafe for women in a maternity care system with a well developed risk
      selection and referral system.

PMID- 25961724
TI  - Post-operative plasma osteopontin predicts distant metastasis in human colorectal
      cancer.
AB  - BACKGROUND: The overall prognosis of colorectal cancer (CRC) patients is
      unsatisfactory due to cancer metastasis after operation. This study aims to
      investigate the clinical significance of plasma osteopontin (OPN) levels as
      minimally invasive, predictive, and surrogate biomarkers for prognosis of CRC
      patients. METHODS: This randomized study design consists of pre-operative and
      post-operative plasma samples from a total of 79 patients. We determined plasma
      levels of OPN by ELISA and examined their correlation with the
      clinicopathological parameters of CRC patients. The effects of endogenous and
      exogenous OPN on CRC metastasis were investigated by examination of the effect on
      regulators of epithelial to messenchymal transition and migration assay. RESULTS:
      Our findings demonstrated for the first time the clinical correlation of plasma
      OPN with metastasis of CRC patients. High post-operative plasma OPN level
      (>153.02 ng/ml) associated with development of metastasis after curative
      resection (p<0.001). Moreover, post-operative plasma OPN level correlated with
      disease-free survival of CRC patients (p=0.009) and was an independent factor for
      predicting development of metastasis in CRC patients after curative resection
      (p=0.036). Our in vitro model showed that OPN ectopic expression induced DLD1
      cell migration through Snail and Twist1 overexpression and E-cadherin repression,
      and secretory OPN level enhanced cell migration. CONCLUSIONS: The results of the
      current study suggest that post-operative plasma OPN correlated with post
      operative metastasis, suggesting that it is a potential non-invasive biomarker
      for the development of future metastasis in CRC patients. In addition, OPN was
      shown to be involved in the metastatic process and thus inhibition of OPN is a
      potential therapeutic approach to treat CRC patients.

PMID- 25961725
TI  - Effect of social influence on effort-allocation for monetary rewards.
AB  - Though decades of research have shown that people are highly influenced by peers,
      few studies have directly assessed how the value of social conformity is weighed
      against other types of costs and benefits. Using an effort-based decision-making
      paradigm with a novel social influence manipulation, we measured how social
      influence affected individuals' decisions to allocate effort for monetary rewards
      during trials with either high or low probability of receiving a reward. We found
      that information about the effort-allocation of peers modulated participant
      choices, specifically during conditions of low probability of obtaining a reward.
      This suggests that peer influence affects effort-based choices to obtain rewards
      especially under conditions of risk. This study provides evidence that people
      value social conformity in addition to other costs and benefits when allocating
      effort, and suggests that neuroeconomic studies that assess trade-offs between
      effort and reward should consider social environment as a factor that can
      influence decision-making. 

PMID- 25961726
TI  - Biogeography and Genetic Structure in Populations of a Widespread Lichen
      (Parmelina tiliacea, Parmeliaceae, Ascomycota).
AB  - The genetic diversity and population structure of the foliose lichenized fungus
      Parmelina tiliacea has been analyzed through its geographical range, including
      samples from Macaronesia (Canary Islands), the Mediterranean, and Eurosiberia.
      DNA sequences from the nuclear ribosomal internal transcribed spacer, the
      mitochondrial large subunit ribosomal RNA gene, and the translation elongation
      factor 1-alpha were used as molecular markers. The haplotypes of the three
      markers and the molecular variance analyses of multilocus haplotypes showed the
      highest diversity in the Canary Islands, while restricted haplotypes occurred at
      high frequencies in Mediterranean coastal samples. The multilocus haplotypes
      formed three unevenly distributed clusters (clusters 1-3). In the Canary Islands
      all the haplotypes were present in a similar proportion, while the coastal
      Mediterranean sites had almost exclusively haplotypes of cluster 3; cluster 2
      predominated in inland Mediterranean sites; and cluster 1 was more abundant in
      central and northern Europe (Eurosiberian area). The distribution of clusters is
      partially explained by climatic factors, and its interaction with local spatial
      structure, but much of the variation remains unexplained. The high frequency of
      individuals in the Canary Islands with haplotypes shared with other areas
      suggests that could be a refugium of genetic diversity, and the high frequency of
      individuals of the Mediterranean coastal sites with restricted haplotypes
      indicates that gene flow to contiguous areas may be restricted. This is
      significant for the selection of areas for conservation purposes, as those with
      most genetic variation may reflect historical factors and biological properties
      of the species. 

PMID- 25961727
TI  - Web-based training for primary healthcare workers in rural China: a qualitative
      exploration of stakeholders' perceptions.
AB  - BACKGROUND: Equitable access to basic public health services is a priority in
      China. However, primary healthcare workers' competence to deliver public health
      services is relatively poor because they lack professional training. Since the
      availability of web-based training has increased in China, the current study
      explored stakeholders' perceptions of a web-based training program on basic
      public health services to understand their thoughts, experiences, and attitudes
      about it. METHODS: Six focus group discussions with primary healthcare workers
      and three with directors of township hospitals, county-level Health Bureaus, and
      county-level Centers for Disease Control and Prevention were conducted in Yichang
      City during 2013. Semi-structured topic guides were used to facilitate
      qualitative data collection. Audio recordings of the sessions were transcribed
      verbatim and theme analysis was performed. RESULTS: Most of the study's
      participants, especially the village doctors, had insufficient knowledge of basic
      public health services. The existing training program for primary healthcare
      workers consisted of ineffective traditional face-to-face sessions and often
      posed accessibility problems for the trainees. Most of the study's participants
      had a positive attitude about web-based learning and expressed a strong desire to
      receive this novel training approach because of its flexibility and convenience.
      The perceived barriers to utilizing the web-based training method included poor
      computer literacy, lack of personal interaction, inadequate infrastructure, and
      lack of time and motivation. The facilitators of this approach included the
      training content applicability, the user-friendly and interactive learning
      format, and policy support. CONCLUSIONS: Web-based training on basic public
      health services is a promising option in rural China. The findings of the study
      will contribute knowledge to implementation of web-based training in similar
      settings.

PMID- 25961728
TI  - Correction: The Distribution of Ocular Chlamydia Prevalence across Tanzanian
      Communities Where Trachoma Is Declining.

PMID- 25961729
TI  - Pore-scale modeling of pore structure effects on P-wave scattering attenuation in
      dry rocks.
AB  - Underground rocks usually have complex pore system with a variety of pore types
      and a wide range of pore size. The effects of pore structure on elastic wave
      attenuation cannot be neglected. We investigated the pore structure effects on P
      wave scattering attenuation in dry rocks by pore-scale modeling based on the wave
      theory and the similarity principle. Our modeling results indicate that pore
      size, pore shape (such as aspect ratio), and pore density are important factors
      influencing P-wave scattering attenuation in porous rocks, and can explain the
      variation of scattering attenuation at the same porosity. From the perspective of
      scattering attenuation, porous rocks can safely suit to the long wavelength
      assumption when the ratio of wavelength to pore size is larger than 15. Under the
      long wavelength condition, the scattering attenuation coefficient increases as a
      power function as the pore density increases, and it increases exponentially with
      the increase in aspect ratio. For a certain porosity, rocks with smaller aspect
      ratio and/or larger pore size have stronger scattering attenuation. When the pore
      aspect ratio is larger than 0.5, the variation of scattering attenuation at the
      same porosity is dominantly caused by pore size and almost independent of the
      pore aspect ratio. These results lay a foundation for pore structure inversion
      from elastic wave responses in porous rocks. 

PMID- 25961730
TI  - Radiation-induced microRNA-622 causes radioresistance in colorectal cancer cells
      by down-regulating Rb.
AB  - The standard treatment for patients with locally advanced rectal cancer is
      preoperative 5-fluorouracil-based chemoradiotherapy followed by total mesorectal
      excision. However, tumor response to standard dose radiation varies. In this
      study, we found that miR-622 was increased significantly in ionizing radiation
      treated colorectal cancer (CRC) cells compared to the cells cultured with
      irradiated medium, and persisted stably in surviving cells treated with
      continuous low-dose radiation. Overexpression of miR-622 induced the
      radioresistance in vitro. In addition, miR-622 inhibited Rb expression by
      directly targeting RB1-3'UTR. Overexpression of Rb reversed miR-622-induced
      radioresistance in vitro. In response to ionizing radiation, the Rb-E2F1-P/CAF
      complex activated proapoptotic genes. Importantly, miR-622 was highly expressed
      in tumors of rectal cancer patients with non-regression after standard dose
      radiotherapy. In conclusion, miR-622 overexpressing cells are induced or selected
      by radiotherapy, causing in turn radioresistance and poor response to further
      therapy. MiR-622 is a potential biomarker of responders for radiotherapy and a
      potential therapeutic target.

PMID- 25961731
TI  - Potential and Actual Neonatal Organ and Tissue Donation After Circulatory
      Determination of Death.
AB  - IMPORTANCE: The need for transplants continues to exceed organ and tissue donor
      availability. Although recent surgical advances have resulted in successful
      transplants using very small pediatric donors, including neonates, the actual
      practice of neonatal organ donation after circulatory determination of death
      (DCDD) remains uncommon. OBJECTIVE: To describe the percentage of neonates
      potentially eligible for DCDD, including those who underwent successful donation,
      and reasons for ineligibility in those who did not in a single neonatal intensive
      care unit (NICU). DESIGN, SETTING, AND PARTICIPANTS: We obtained data from the
      Children's Hospital Neonatal Database and Intermountain Donor Services (IDS)
      organ procurement records. The 136 deaths that occurred in the NICU of the
      Primary Children's Hospital, Salt Lake City, Utah, from January 1, 2010, through
      May 7, 2013, were reviewed retrospectively from January 12 through July 1, 2014,
      to determine potential eligibility for DCDD as determined by IDS minimum
      eligibility criteria (requirement of life-sustaining interventions and weight >2
      kg). For patients who did not undergo DCDD, we reviewed records to determine the
      reasons for ineligibility. MAIN OUTCOMES AND MEASURES: Potential eligibility for
      DCDD among neonates who died in the study NICU. RESULTS: Of 136 deaths in the
      NICU, 60 (44.1%) met criteria for DCDD; however, fewer than 10% were referred
      appropriately to the regional organ procurement organization for evaluation.
      Forty-five neonates (33.1%) ultimately died within 90 minutes of withdrawal of
      life-sustaining interventions and thus would have been eligible for organ
      donation based on warm ischemic time. The most common causes of death among the
      60 potentially eligible neonatal donors were neonatal encephalopathy (n = 17) and
      multiple congenital anomalies (n = 14). Nonreferral or late referral by the
      medical team was the most frequent reason for donor ineligibility, including 49
      neonates (36.0%). Overall, only 4 neonates (2.9%) underwent successful DCDD.
      CONCLUSIONS AND RELEVANCE: Although almost half of all neonatal deaths identified
      met minimum IDS criteria, most of these patients were not referred or were
      referred too late for evaluation. Although small size remains the primary reason
      for exclusion from DCDD, improved education with regard to criteria and the
      importance of timely referral by neonatologists and other members of the NICU
      team would likely result in a significant increase of future donations.

PMID- 25961733
TI  - Correction: the impact of host diet on wolbachia titer in Drosophila.

PMID- 25961732
TI  - Prevalence and Predictors of Immunological Failure among HIV Patients on HAART in
      Southern Ethiopia.
AB  - Immunological monitoring is part of the standard of care for patients on
      antiretroviral treatment. Yet, little is known about the routine implementation
      of immunological laboratory monitoring and utilization in clinical care in
      Ethiopia. This study assessed the pattern of immunological monitoring,
      immunological response, level of immunological treatment failure and factors
      related to it among patients on antiretroviral therapy in selected hospitals in
      southern Ethiopia. A retrospective longitudinal analytic study was conducted
      using documents of patients started on antiretroviral therapy. Adequacy of timely
      immunological monitoring was assessed every six months the first year and every
      one year thereafter. Immunological response was assessed every six months at
      cohort level. Immunological failure was based on the criteria: fall of follow-up
      CD4 cell count to baseline (or below), or CD4 levels persisting below 100
      cells/mm3, or 50% fall from on-treatment peak value. A total of 1,321 documents
      of patients reviewed revealed timely immunological monitoring were inadequate.
      There was adequate immunological response, with pediatric patients, females,
      those with less advanced illness (baseline WHO Stage I or II) and those with
      higher baseline CD4 cell count found to have better immunological recovery.
      Thirty-nine patients (3%) were not evaluated for immunological failure because
      they had frequent treatment interruption. Despite overall adequate immunological
      response at group level, the prevalence of those who ever experienced
      immunological failure was 17.6% (n=226), while after subsequent re-evaluation it
      dropped to 11.5% (n=147). Having WHO Stage III/IV of the disease or a higher CD4
      cell count at baseline was identified as a risk for immunological failure. Few
      patients with confirmed failure were switched to second line therapy. These
      findings highlight the magnitude of the problem of immunological failure and the
      gap in management. Prioritizing care for high risk patients may help in effective
      utilization of meager resources. 

PMID- 25961734
TI  - Whole-Arm Ultrasound to Rule Out Suspected Upper-Extremity Deep Venous Thrombosis
      in Outpatients.

PMID- 25961735
TI  - Intravoxel Incoherent Motion Diffusion Weighted MR Imaging at 3.0 T: Assessment
      of Steatohepatitis and Fibrosis Compared with Liver Biopsy in Type 2 Diabetic
      Patients.
AB  - OBJECTIVE: To evaluate the capability of intravoxel incoherent motion (IVIM)
      diffusion-weighted imaging (DWI) to assess steatohepatitis and fibrosis
      determined by histopathology in type 2 diabetic patients. METHODS: Fifty-nine
      type 2 diabetic patients (49 women, 10 men; mean age, 54 +/- 9 years) were
      submitted to liver biopsy for the evaluation of non-alcoholic fatty liver disease
      (NAFLD) and underwent DWI on a 3.0T MR system using 10 b values. Institutional
      approval and patient consent were obtained. Pure molecular-based (D), perfusion
      related (D*), and vascular fraction (f) were calculated using a double
      exponential model and least squares curve fitting. D, D*, and f were compared
      between patients with and without steatohepatitis and between patients with and
      without fibrosis. The variables were compared by using the Ranksum test and
      Student t-test. RESULTS: Steatohepatitis was observed in 22 patients and fibrosis
      in 16 patients. A lower D median (0.70 s/mm2 vs. 0.83 s/mm2, p<0.05) and a lower
      D* median (34.39 s/mm2 vs. 45.23 s/mm2, p<0.05) were observed among those with
      steatohepatitis. A lower D median (0.70 s/mm2 vs. 0.82 s/mm2, p<0.05) and a lower
      D* median (35.01 s/mm2 vs. 44.76 s/mm2, p=0.05) were also observed among those
      with fibrosis. CONCLUSION: IVIM-DWI has the potential to aid in the
      characterization of steatohepatitis and fibrosis.

PMID- 25961737
TI  - Sexual Orientation Identity Disparities in Awareness and Initiation of the Human
      Papillomavirus Vaccine Among U.S. Women and Girls: A National Survey.
AB  - BACKGROUND: Lesbians and bisexual women are at risk for human papillomavirus
      (HPV) infection from female and male sexual partners. OBJECTIVE: To examine the
      association between sexual orientation identity and HPV vaccination among U.S.
      women and girls. DESIGN: Cross-sectional, using 2006-2010 National Survey of
      Family Growth data. SETTING: U.S. civilian noninstitutionalized population.
      PARTICIPANTS: The 2006-2010 National Survey of Family Growth used stratified
      cluster sampling to establish a national probability sample of 12,279 U.S. women
      and girls aged 15 to 44 years. Analyses were restricted to 3253 women and girls
      aged 15 to 25 years who were asked about HPV vaccination. MEASUREMENTS:
      Multivariable logistic regression was used to obtain prevalence estimates of HPV
      vaccine awareness and initiation adjusted for sociodemographic and health care
      factors for each sexual orientation identity group. RESULTS: Among U.S. women and
      girls aged 15 to 25 years, 84.4% reported having heard of the HPV vaccine; of
      these, 28.5% had initiated HPV vaccination. The adjusted prevalence of vaccine
      awareness was similar among heterosexual, bisexual, and lesbian respondents.
      After adjustment for covariates, 8.5% (P = 0.007) of lesbians and 33.2% (P =
      0.33) of bisexual women and girls who had heard of the vaccine had initiated
      vaccination compared with 28.4% of their heterosexual counterparts. LIMITATION:
      Self-reported, cross-sectional data, and findings may not be generalizable to
      periods after 2006 to 2010 or all U.S. lesbians aged 15 to 25 years (because of
      the small sample size for this group). CONCLUSION: Adolescent and young adult
      lesbians may be less likely to initiate HPV vaccination than their heterosexual
      counterparts. Programs should facilitate access to HPV vaccination services among
      young lesbians. PRIMARY FUNDING SOURCE: National Cancer Institute.

PMID- 25961736
TI  - Physical activity, sedentary time and physical capability in early old age:
      British birth cohort study.
AB  - PURPOSE: To investigate the associations of time spent sedentary, in moderate-to
      vigorous-intensity physical activity (MVPA) and physical activity energy
      expenditure (PAEE) with physical capability measures at age 60-64 years. METHODS:
      Time spent sedentary and in MVPA and, PAEE were assessed using individually
      calibrated combined heart rate and movement sensing among 1727 participants from
      the MRC National Survey of Health and Development in England, Scotland and Wales
      as part of a detailed clinical assessment undertaken in 2006-2010. Multivariable
      linear regression models were used to examine the cross-sectional associations
      between standardised measures of each of these behavioural variables with grip
      strength, chair rise and timed up-&-go (TUG) speed and standing balance time.
      RESULTS: Greater time spent in MVPA was associated with higher levels of physical
      capability; adjusted mean differences in each capability measure per 1 standard
      deviation increase in MVPA time were: grip strength (0.477 kg, 95% confidence
      interval (CI): 0.015 to 0.939), chair rise speed (0.429 stands/min, 95% CI: 0.093
      to 0.764), standing balance time (0.028 s, 95% CI: 0.003 to 0.053) and TUG speed
      (0.019 m/s, 95% CI: 0.011 to 0.026). In contrast, time spent sedentary was
      associated with lower grip strength (-0.540 kg, 95% CI: -1.013 to -0.066) and TUG
      speed (-0.011 m/s, 95% CI: -0.019 to -0.004). Associations for PAEE were similar
      to those for MVPA. CONCLUSION: Higher levels of MVPA and overall physical
      activity (PAEE) are associated with greater levels of physical capability whereas
      time spent sedentary is associated with lower levels of capability. Future
      intervention studies in older adults should focus on both the promotion of
      physical activity and reduction in time spent sedentary.

PMID- 25961738
TI  - Correlation of Alzheimer's disease death rates with historical per capita
      personal income in the USA.
AB  - Alzheimer's disease (AD) is a progressive degenerating disease of complex
      etiology. A variety of risk factors contribute to the chance of developing AD.
      Lifestyle factors, such as physical, mental and social activity, education, and
      diet all affect the susceptibility to developing AD. These factors are in turn
      related to the level of personal income. Lower income usually coincides with
      lower level of education, lesser mental, leisure-social and physical activity,
      and poorer diet. In the present paper, we have analyzed the correlation of
      historical (1929-2011) per capita personal income (PCPI) for all states of the
      USA with corresponding age-adjusted AD death rates (AADR) for years 2000, 2005
      and 2008. We found negative correlations in all cases, the highest one (R ~ 
      0.65) for the PCPIs in the year 1970 correlated against the AADRs in 2005. From
      1929 to 2005 the R value varies in an oscillatory manner, with the strongest
      correlations in 1929, 1970, 1990 and the weakest in 1950, 1980, 1998. Further
      analysis indicated that this oscillatory behavior of R is not artificially
      related to the economic factors but rather to delayed biological consequences
      associated with personal income. We conclude that the influence of the income
      level on the AD mortality in 2005 was the highest in the early years of life of
      the AD victims. Overall, the income had a significant, lifelong, albeit
      constantly decreasing, influence on the risk of developing AD. We postulate that
      the susceptibility of a population to late-onset AD (LOAD) is determined to a
      large extent by the history of income-related modifiable lifestyle risk factors.
      Among these risk factors, inappropriate diet has a significant contribution. 

PMID- 25961739
TI  - Comparisons of different metabolic syndrome definitions and associations with
      coronary heart disease, stroke, and peripheral arterial disease in a rural
      Chinese population.
AB  - OBJECTIVES: We estimated the prevalence of metabolic syndrome (MetS) and compared
      associations of different MetS definitions with coronary heart disease (CHD),
      stroke, and peripheral arterial disease (PAD) in a rural Chinese population.
      METHODS: Among 4,748 residents (2,145 men and 2,603 women) aged 30+ years in
      rural China from 2006 to 2007, the prevalence of MetS was estimated by using five
      different definitions: modified World Health Organization (WHO), Chinese Diabetes
      Society (CDS), the updated National Cholesterol Education Program Adult Treatment
      Panel III (NCEP-ATP III) for Asian-Americans, International Diabetes Federation
      (IDF), and Joint Interim Statement (JIS). Multivariable logistic regression
      analyses were implemented to estimate the association between MetS and the
      prevalence of CHD, stroke and PAD, respectively. RESULTS: Prevalence of MetS in
      men was 11.5% (WHO), 14.8% (CDS), 32.4% (NCEP-ATP III), 27.5% (IDF) and 39.7%
      (JIS) and in women was 15.7% (WHO), 20.7% (CDS), 54.2% (NCEP-ATP III), 51.5%
      (IDF) and 54.2% (JIS), respectively. Respective ORs (95% CI) for associating MetS
      with CHD in men were 1.79 (1.02-3.17), 1.25 (0.69-2.26), 1.61 (1.01-2.58), 1.84
      (1.14-2.96), and 1.53 (0.96-2.43). Corresponding ORs (95% CI) for stroke in men
      were 2.18 (95% CI 1.20 to 3.97), 2.20 (95% CI 1.25 to 3.89), 1.71 (95% CI 1.02 to
      2.84), 1.30 (95% CI 0.77 to 2.23), and 1.61 (95% CI 0.97 to 2.68), respectively.
      In women, CHD and stroke were significantly associated with MetS using all five
      definitions of MetS. In addition, PAD was associated with all five MetS
      definitions in men, but not in women. Only hyperglycemia and BMI were
      significantly associated with PAD in women. CONCLUSIONS: In this rural Chinese
      population, the JIS, IDF and CDS criteria may not be more suitable than WHO and
      updated NCEP-ATPIII definitions for screening high-risk individuals and
      estimating the risk of CHD and stroke from MetS, especially in men.

PMID- 25961741
TI  - Abdominal drainage versus no drainage post-gastrectomy for gastric cancer.
AB  - BACKGROUND: Gastrectomy remains the primary therapeutic method for resectable
      gastric cancer. Thought of as an important measure to reduce post-operative
      complications and mortality, abdominal drainage has been used widely after
      gastrectomy for gastric cancer in previous decades. The benefits of abdominal
      drainage have been questioned by researchers in recent years. OBJECTIVES: The
      objectives of this review were to assess the benefits and harms of routine
      abdominal drainage post-gastrectomy for gastric cancer. SEARCH METHODS: We
      searched the Cochrane Upper Gastrointestinal and Pancreatic Diseases (UGPD) Group
      Specialised Register and the Cochrane Central Register of Controlled Trials
      (CENTRAL) in The Cochrane Library (2014, Issue 11); MEDLINE (via PubMed) (1950 to
      November 2014); EMBASE (1980 to November 2014); and the Chinese National
      Knowledge Infrastructure (CNKI) Database (1979 to November 2014). SELECTION
      CRITERIA: We included randomised controlled trials (RCTs) comparing an abdominal
      drain versus no drain in patients who had undergone gastrectomy (not considering
      the scale of gastrectomy and the extent of lymphadenectomy); irrespective of
      language, publication status, and the type of drain. We excluded RCTs comparing
      one drain with another. DATA COLLECTION AND ANALYSIS: We adhered to the standard
      methodological procedures of The Cochrane Collaboration. From each included
      trial, we extracted the data on the methodological quality and characteristics of
      the participants, mortality (30-day mortality), re-operations, post-operative
      complications (pneumonia, wound infection, intra-abdominal abscess, anastomotic
      leak, drain-related complications), operation time, length of post-operative
      hospital stay, and initiation of a soft diet. For dichotomous data, we calculated
      the risk ratio (RR) and 95% confidence interval (CI). For continuous data, we
      calculated mean difference (MD) and 95% CI. We tested heterogeneity using the
      Chi(2) test. We used a fixed-effect model for data analysis with RevMan software,
      but we used a random-effects model if the P value of the Chi(2) test was less
      than 0.1. MAIN RESULTS: We included four RCTs involving 438 patients (220
      patients in the drain group and 218 in the no-drain group). There was no evidence
      of a difference between the two groups in mortality (RR 1.73, 95% CI 0.38 to
      7.84); re-operations (RR 2.49, 95% CI 0.71 to 8.74); post-operative complications
      (pneumonia: RR 1.18, 95% CI 0.55 to 2.54; wound infection: RR 1.23, 95% CI 0.47
      to 3.23; intra-abdominal abscess: RR 1.27, 95% CI 0.29 to 5.51; anastomotic leak:
      RR 0.93, 95% CI 0.06 to 14.47); or initiation of soft diet (MD 0.15 days, 95% CI 
      0.07 to 0.37). However, the addition of a drain prolonged the operation time (MD
      9.07 min, 95% CI 2.56 to 15.57) and post-operative hospital stay (MD 0.69 day,
      95% CI 0.18 to 1.21) and led to drain-related complications. Additionally, we
      should note that 30-day mortality and re-operations are very rare events and, as
      a result, very large numbers of patients would be required to make any sensible
      conclusions about whether the two groups were similar. The overall quality of the
      evidence according to the GRADE approach was 'very low' for mortality and re
      operations, and 'low' for post-operative complications, operation time, and post
      operative length of stay. AUTHORS' CONCLUSIONS: We found no convincing evidence
      to support routine drain use after gastrectomy for gastric cancer.

PMID- 25961743
TI  - Antecedents and Consequences of Envy.
AB  - The aim of this study was to examine the relationship between individual
      attributes and envy, and to determine how envy may impact personal response
      variables in the workplace. To address these issues we apply Vecchio's theory on
      antecedents and consequences of envy (1995) as a theoretical framework. The
      present study relied on a cross-sectional measurement design. A total of 135
      leaders and 772 followers employed in business organizations participated. SEM
      analysis shows that span of supervision serves as an important antecedent of
      envy, where span of supervision is significantly associated to envy via
      supportive leadership. Furthermore, envy seems to be indirectly and negatively
      related to self-esteem via distress and directly related to social loafing. The
      implications of these findings are discussed, and suggestions for future research
      are outlined. 

PMID- 25961742
TI  - Revealing the Molecular Portrait of Triple Negative Breast Tumors in an
      Understudied Population through Omics Analysis of Formalin-Fixed and Paraffin
      Embedded Tissues.
AB  - Triple negative breast cancer (TNBC), defined by the lack of expression of the
      estrogen receptor, progesterone receptor and human epidermal receptor 2, is an
      aggressive form of breast cancer that is more prevalent in certain populations,
      in particular in low- and middle-income regions. The detailed molecular features
      of TNBC in these regions remain unexplored as samples are mostly accessible as
      formalin-fixed paraffin embedded (FFPE) archived tissues, a challenging material
      for advanced genomic and transcriptomic studies. Using dedicated reagents and
      analysis pipelines, we performed whole exome sequencing and miRNA and mRNA
      profiling of 12 FFPE tumor tissues collected from pathological archives in
      Mexico. Sequencing analyses of the tumor tissues and their blood pairs identified
      TP53 and RB1 genes as the most frequently mutated genes, with a somatic mutation
      load of 1.7 mutations/exome Mb on average. Transcriptional analyses revealed an
      overexpression of growth-promoting signals (EGFR, PDGFR, VEGF, PIK3CA, FOXM1), a
      repression of cell cycle control pathways (TP53, RB1), a deregulation of DNA
      repair pathways, and alterations in epigenetic modifiers through miRNA:mRNA
      network de-regulation. The molecular programs identified were typical of those
      described in basal-like tumors in other populations. This work demonstrates the
      feasibility of using archived clinical samples for advanced integrated genomics
      analyses. It thus opens up opportunities for investigating molecular features of
      tumors from regions where only FFPE tissues are available, allowing retrospective
      studies on the search for treatment strategies or on the exploration of the
      geographic diversity of breast cancer. 

PMID- 25961744
TI  - Blocking Respiratory Syncytial Virus Entry: A Story with Twists.
AB  - Respiratory syncytial virus (RSV) is responsible for majority of infant
      hospitalizations due to viral infections. Despite its clinical importance, no
      vaccine against RSV or effective antiviral therapy is available. Several
      structural classes of small-molecule RSV entry inhibitor have been described and
      one compound has advanced to clinical testing. Mutations in either one of two
      resistance hot spots in the F protein mediate unusual pan-resistance to all of
      these inhibitor classes. Based on the biochemical characterization of resistant
      viruses and structural insight into the RSV F trimer, we propose a kinetic escape
      model as the origin of pan-resistance. Since a resistant RSV remained pathogenic
      in the mouse model, pan-resistance mutations could emerge rapidly in circulating
      RSV strains. We evaluate clinical implications and discuss consequences for the
      design of future RSV drug discovery campaigns. 

PMID- 25961745
TI  - High glucose induces bone marrow-derived mesenchymal stem cell senescence by
      upregulating autophagy.
AB  - Hyperglycemia was reported to cause bone marrow hematopoietic niche dysfunction,
      and high glucose (HG) in the cultured medium induces MSC senescence. The
      underlying mechanism is unclear. Here, we investigated the role of HG-induced
      autophagy in bone-marrow-derived mesenchymal stem cell (BMSC) senescence. HG (25
      mM) increased expression of Beclin-1, Atg 5, 7 and 12, generation of LC3-II and
      autophagosome formation which was correlated with development of cell senescence.
      Pretreatment of HG-MSC with 3-methyladenine (3-MA) prevented senescence but
      increased apoptosis. N-acetylcysteine (NAC) was effective in abrogating HG
      induced autophagy accompanied by prevention of senescence. Diphenyleneiodonium
      (DPI), an inhibitor of NADPH oxidase, blocked autophagy and senescence in a
      manner comparable to NAC. 3-MA, NAC and DPI inhibited HG-induced interleukin-6
      production in BMSCs. These results suggest that hyperglycemia induces MSC
      senescence and local inflammation via a novel oxidant-mediated autophagy which
      contributes to bone marrow niche dysfunction and hematopoietic impairment. 

PMID- 25961746
TI  - Increase EGFR Mutations Detection Rate in Lung Adenocarcinoma by Real-Time PCR
      Screening Followed by Direct Sequencing.
AB  - BACKGROUND: Recently, a number of small-molecule tyrosine kinase inhibitors
      (TKIs) have been developed to target the ATP-binding cleft of the epidermal
      growth factor receptor (EGFR). The presence of EGFR mutations in non-small cell
      lung cancer (NSCLC) correlates with the responsiveness to TKIs. Therefore, the
      identification of EGFR mutations before the administration of TKIs of NSCLC has
      become important. The aim of the present study was to investigate the occurrence
      of EGFR mutations in the southern Taiwanese population with NSCLC using a
      combination of real-time polymerase chain reaction (PCR) kit and direct
      sequencing. METHODS: In the present study, DNAs were extracted from 249 cases of
      formalin-fixed, paraffin-embedded NSCLC samples for clinical EGFR mutational
      analysis by real-time PCR kit and direct sequencing. RESULTS: The results showed
      that the frequency of EGFR mutations is 63% in the southern Taiwanese population.
      Most of the EGFR mutations are located at exons 19 and 21. In addition, we
      indicated that a combination of real-time PCR kit and direct sequencing increases
      the rate of mutation by 4%. Direct sequencing revealed 9 EGFR mutations including
      6 reported EGFR mutations and 3 novel EGFR mutations. CONCLUSIONS: In the present
      study, we have demonstrated that a combination of real-time PCR kit and direct
      sequencing increases the detection rate of EGFR mutations. Therefore, our
      proposed EGFR mutation detection strategy could be applied in clinical settings.
      In addition, our results indicated the prevalence of EGFR mutational status in
      the southern Taiwanese population.

PMID- 25961747
TI  - Regulatory considerations in oncologic biosimilar drug development.
AB  - Biosimilar monoclonal antibodies are being developed globally for patients with
      different types of solid tumors and hematologic malignancies. Applications for
      proposed biosimilar monoclonal antibodies are being submitted to the regulatory
      authorities around the world and may increase patient access to key treatment
      options upon approval. An understanding among stakeholders (e.g., physicians,
      patients and their caregivers, pharmacists, payers) of the approval criteria, as
      well as the similarities and differences in regulatory pathways involved in
      biosimilar approval in different countries, as presented in this review, will
      facilitate identification of high-quality, safe, monoclonal antibodies that have
      been developed according to strict, biosimilar regulatory standards. Further
      guidance and resolution of the ongoing discussions on biosimilar labeling,
      naming, automatic substitution, and indication extrapolation may ensure, in the
      future, an effective and appropriate use of biosimilar monoclonal antibodies by
      oncologists and other stakeholders in daily clinical practice. 

PMID- 25961748
TI  - Dermoscopic features of eruptive milium-like syringoma.

PMID- 25961749
TI  - Methadone for Patients with Malignant Psoas Syndrome: Case Series of Three
      Patients.
AB  - BACKGROUND: Malignant psoas syndrome (MPS) is a relatively rare syndrome that
      accompanies malignancy; the pain associated with MPS is often difficult to
      control. Methadone is known to be effective in relieving both nociceptive and
      neuropathic pain. OBJECTIVE: Herein we describe treatment strategies for three
      patients with MPS, diagnosed by imaging and clinical findings, who responded to
      methadone treatment. METHODS: Patient diagnoses, pain characteristics, and
      treatment were analyzed retrospectively. Subjects were three patients with MPS
      who presented to Hyogo Cancer Center with pain. A numeric rating scale (NRS; 0
      10) was used to assess patients' pain levels. RESULTS: All three patients were
      diagnosed with malignancies (prostate, cervical, and urachal) and had impaired
      gait and thigh extension. All had tumor invasion to the iliopsoas muscle, as
      determined by imaging, and were diagnosed with MPS. After starting methadone,
      symptoms improved in all patients and they were able to extend the thigh and walk
      normally. The NRS scores improved by an average of -7.3 points (95% confidence
      interval [CI] -4.97, -9.69) on Day 14; and the average time until symptom
      improvement after starting methadone was 2.3 days (95% CI 1.86, 2.80).
      CONCLUSIONS: Methadone may be considered a treatment choice for MPS patients in
      whom pain is difficult to control.

PMID- 25961750
TI  - Characterization of Cichopeptins, New Phytotoxic Cyclic Lipodepsipeptides
      Produced by Pseudomonas cichorii SF1-54 and Their Role in Bacterial Midrib Rot
      Disease of Lettuce.
AB  - The lettuce midrib rot pathogen Pseudomonas cichorii SF1-54 produces seven
      bioactive compounds with biosurfactant properties. Two compounds exhibited
      necrosis-inducing activity on chicory leaves. The structure of the two phytotoxic
      compounds, named cichopeptin A and B, was tentatively characterized. They are
      related cyclic lipopeptides composed of an unsaturated C12-fatty acid chain
      linked to the N-terminus of a 22-amino acid peptide moiety. Cichopeptin B differs
      from cichopeptin A only in the last C-terminal amino acid residue, which is
      probably Val instead of Leu/Ile. Based on peptide sequence similarity,
      cichopeptins are new cyclic lipopeptides related to corpeptin, produced by the
      tomato pathogen Pseudomonas corrugata. Production of cichopeptin is stimulated by
      glycine betaine but not by choline, an upstream precursor of glycine betaine.
      Furthermore, a gene cluster encoding cichopeptin synthethases, cipABCDEF, is
      responsible for cichopeptin biosynthesis. A cipA-deletion mutant exhibited
      significantly less virulence and rotten midribs than the parental strain upon
      spray inoculation on lettuce. However, the parental and mutant strains multiplied
      in lettuce leaves at a similar rate. These results demonstrate that cichopeptins
      contribute to virulence of P. cichorii SF1-54 on lettuce. 

PMID- 25961751
TI  - MiR-144 Inhibits Uveal Melanoma Cell Proliferation and Invasion by Regulating c
      Met Expression.
AB  - MicroRNAs (miRNAs) are a group endogenous small non-coding RNAs that inhibit
      protein translation through binding to specific target mRNAs. Recent studies have
      demonstrated that miRNAs are implicated in the development of cancer. However,
      the role of miR-144 in uveal melanoma metastasis remains largely unknown. MiR-144
      was downregulated in both uveal melanoma cells and tissues. Transfection of miR
      144 mimic into uveal melanoma cells led to a decrease in cell growth and
      invasion. After identification of two putative miR-144 binding sites within the
      3' UTR of the human c-Met mRNA, miR-144 was proved to inhibit the luciferase
      activity inMUM-2B cells with a luciferase reporter construct containing the
      binding sites. In addition, the expression of c-Met protein was inhibited by miR
      144. Furthermore, c-Met-mediated cell proliferation and invasion were inhibited
      by restoration of miR-144 in uveal melanoma cells. In conclusion, miR-144 acts as
      a tumor suppressor in uveal melanoma, through inhibiting cell proliferation and
      migration. miR-144 might serve as a potential therapeutic target in uveal
      melanoma patients. 

PMID- 25961753
TI  - Mechanical Stretching of Mouse Calvarial Osteoblasts In Vitro Models Changes in
      MMP-2 and MMP-9 Expression at the Bone-Implant Interface.
AB  - Bone to mechanical loading elicits a biological response that has clinical
      significance for several areas in dental medicine, including orthodontic tooth
      movement, tempromandibular joint disease, and endosseous dental implant
      osseointegration. Human orthopedic studies of failed hip implant sites have
      identified increased mRNA expression of several collagen-degrading matrix
      metalloproteinases (MMPs), while in vitro experiments have shown increases in MMP
      secretion after exposure to inflammatory mediators. This investigation evaluates
      the effects of mechanical deformation on in vitro osteoblasts by assessing
      changes in MMP gene expression and enzyme activity. We seeded mouse neonatal
      calvarial osteoblasts onto flexible 6-well plates and subjected to continuous
      cyclic mechanical stretching. The expression and activity of mRNA for several
      MMPs (2, 3, 9, and 10) was assessed. When subjected to mechanical stress in
      culture, only mRNA specific for MMP-9 was significantly increased compared to
      nonstretched controls (P < .005). Measurement of MMP activity by gelatin
      zymography demonstrated that none of the MMPs showed increased activity with
      stretching; however, MMP-2 activity decreased. Our results suggest that in
      response to stretch, MMP-2 responds rapidly by inhibiting conversion of a MMP-2
      to the active form, while a slower up-regulation of MMP-9 may play a role in the
      long-term remodeling of extracellular matrix in response to continuous mechanical
      loading. This study suggests that the regulation of metalloproteinases at both
      the mRNA and protein level are important in the response of bone to mechanical
      stress. 

PMID- 25961752
TI  - Rapid detection of health-care-associated bloodstream infection in critical care
      using multipathogen real-time polymerase chain reaction technology: a diagnostic
      accuracy study and systematic review.
AB  - BACKGROUND: There is growing interest in the potential utility of real-time
      polymerase chain reaction (PCR) in diagnosing bloodstream infection by detecting
      pathogen deoxyribonucleic acid (DNA) in blood samples within a few hours.
      SeptiFast (Roche Diagnostics GmBH, Mannheim, Germany) is a multipathogen probe
      based system targeting ribosomal DNA sequences of bacteria and fungi. It detects
      and identifies the commonest pathogens causing bloodstream infection. As
      background to this study, we report a systematic review of Phase III diagnostic
      accuracy studies of SeptiFast, which reveals uncertainty about its likely
      clinical utility based on widespread evidence of deficiencies in study design and
      reporting with a high risk of bias. OBJECTIVE: Determine the accuracy of
      SeptiFast real-time PCR for the detection of health-care-associated bloodstream
      infection, against standard microbiological culture. DESIGN: Prospective
      multicentre Phase III clinical diagnostic accuracy study using the standards for
      the reporting of diagnostic accuracy studies criteria. SETTING: Critical care
      departments within NHS hospitals in the north-west of England. PARTICIPANTS:
      Adult patients requiring blood culture (BC) when developing new signs of systemic
      inflammation. MAIN OUTCOME MEASURES: SeptiFast real-time PCR results at
      species/genus level compared with microbiological culture in association with
      independent adjudication of infection. Metrics of diagnostic accuracy were
      derived including sensitivity, specificity, likelihood ratios and predictive
      values, with their 95% confidence intervals (CIs). Latent class analysis was used
      to explore the diagnostic performance of culture as a reference standard.
      RESULTS: Of 1006 new patient episodes of systemic inflammation in 853 patients,
      922 (92%) met the inclusion criteria and provided sufficient information for
      analysis. Index test assay failure occurred on 69 (7%) occasions. Adult patients
      had been exposed to a median of 8 days (interquartile range 4-16 days) of
      hospital care, had high levels of organ support activities and recent antibiotic
      exposure. SeptiFast real-time PCR, when compared with culture-proven bloodstream
      infection at species/genus level, had better specificity (85.8%, 95% CI 83.3% to
      88.1%) than sensitivity (50%, 95% CI 39.1% to 60.8%). When compared with pooled
      diagnostic metrics derived from our systematic review, our clinical study
      revealed lower test accuracy of SeptiFast real-time PCR, mainly as a result of
      low diagnostic sensitivity. There was a low prevalence of BC-proven pathogens in
      these patients (9.2%, 95% CI 7.4% to 11.2%) such that the post-test probabilities
      of both a positive (26.3%, 95% CI 19.8% to 33.7%) and a negative SeptiFast test
      (5.6%, 95% CI 4.1% to 7.4%) indicate the potential limitations of this technology
      in the diagnosis of bloodstream infection. However, latent class analysis
      indicates that BC has a low sensitivity, questioning its relevance as a reference
      test in this setting. Using this analysis approach, the sensitivity of the
      SeptiFast test was low but also appeared significantly better than BC. Blood
      samples identified as positive by either culture or SeptiFast real-time PCR were
      associated with a high probability (> 95%) of infection, indicating higher
      diagnostic rule-in utility than was apparent using conventional analyses of
      diagnostic accuracy. CONCLUSION: SeptiFast real-time PCR on blood samples may
      have rapid rule-in utility for the diagnosis of health-care-associated
      bloodstream infection but the lack of sensitivity is a significant limiting
      factor. Innovations aimed at improved diagnostic sensitivity of real-time PCR in
      this setting are urgently required. Future work recommendations include
      technology developments to improve the efficiency of pathogen DNA extraction and
      the capacity to detect a much broader range of pathogens and drug resistance
      genes and the application of new statistical approaches able to more reliably
      assess test performance in situation where the reference standard (e.g. blood
      culture in the setting of high antimicrobial use) is prone to error. STUDY
      REGISTRATION: The systematic review is registered as PROSPERO CRD42011001289.
      FUNDING: The National Institute for Health Research Health Technology Assessment
      programme. Professor Daniel McAuley and Professor Gavin D Perkins contributed to
      the systematic review through their funded roles as codirectors of the Intensive
      Care Foundation (UK).

PMID- 25961754
TI  - Psychological and sociocultural adjustment of first-year international students:
      Trajectories and predictors.
AB  - Despite the increasing number of international students in U.S. universities, the
      temporal course of international students' adjustment has not been adequately
      tested, and only 1 study to date has examined multiple trajectories of
      adjustment. Therefore, the first goal of the current study was to explore
      multiple trajectories of adjustment among first-year international students using
      a broader range of adjustment measures (i.e., psychological distress, positive
      psychological adjustment, sociocultural adjustment). The second goal was to
      identify important predictors of trajectories. A wide range of individual and
      interpersonal predictor variables was examined, including academic stress and
      perceived control over academic stress, personality, social relationships, and
      language-related factors. Undergraduate and graduate international students in
      their first semester at a large midwestern university participated in this 5-wave
      longitudinal study (N = 248) that spanned 1 academic year. Multiple trajectories
      emerged, and the trajectories varied across the 3 adjustment measures. Average
      trajectories masked the trajectories of small groups of students who maintained
      or increased in terms of adjustment difficulties across outcomes. Contrary to
      popular theories, the U-shape adjustment trajectory (characterized by initial
      euphoria, distress, and then recovery) did not emerge. The most consistent
      predictors of adjustment trajectories were perceived present control over
      academic stress and Neuroticism.

PMID- 25961755
TI  - Feasibility of an acceptance and commitment therapy adjunctive web-based program
      for counseling centers.
AB  - Web-based adjunctive tools provide a promising method for addressing the
      challenges college counseling centers face in meeting the mental health needs of
      students. The current study tested an initial adjunctive prototype based on
      acceptance and commitment therapy (ACT) in a pre-post open trial with 30
      counselors and 82 student clients across 4 counseling centers. Results indicated
      high ratings of program satisfaction and usability with counselors and students.
      The majority of students completed at least part of the program. Significant
      improvements were found across almost all outcome and ACT process measures with
      student clients. Improvements in student outcomes were predicted by both changes
      in psychological inflexibility and how often counselors discussed the program
      with students. Results are discussed in relation to support for and future
      development of a flexible, adjunctive ACT program for counseling centers.

PMID- 25961756
TI  - Intergroup forgiveness of race-related offenses.
AB  - We developed a new intergroup forgiveness measure in the context of identity
      related offenses, with a focus on racial conflicts. In Study 1 (N = 384), we
      adapted a widely used measure of interpersonal forgiveness to develop the Group
      Forgiveness Scale (GFS) within the context of an identity-related offense. In
      Study 2, we replicated the 3-factor structure of the GFS (i.e., Avoidance,
      Revenge, Decision to Forgive) and examined evidence for its construct validity in
      a sample of African American/Black university students (N = 225). As evidence of
      convergent validity, intergroup forgiveness correlated with appraising greater
      relationship value as well as appraising lower likelihood of being exploited in
      the future. As evidence of discriminant validity, the newly developed intergroup
      forgiveness scale (i.e., the GFS) correlated only moderately with interpersonal
      forgiveness and perceived microaggressions. In Study 3, in another sample of
      racial/ethnic minority individuals (N = 352), we examined the predictive validity
      of the scale. More specifically, we examined relations of the GFS subscales with
      religious commitment and racial/ethnic identity. The Decision to Forgive subscale
      uniquely correlated with religious commitment controlling for the Avoidance and
      Revenge subscales. Lower revenge correlated with stronger racial/ethnic identity.
      We conclude with implications of the current findings for the development of
      intergroup forgiveness measurement and for understanding the nature of
      forgiveness within marginalized groups.

PMID- 25961757
TI  - Hurdles that impede economic evaluations of welfare interventions.
AB  - Compared with economic evaluations of healthcare interventions, less experience
      has been gained in the field of economic evaluation of welfare interventions.
      This review suggests possible approaches to address four previously identified
      hurdles in economic evaluations of welfare interventions. After literature was
      searched through MEDLINE and EMBASE, it was found that Health-Related-Quality-of
      Life questionnaires related to the condition of the target population are needed,
      instead of generic instruments. These condition-specific instruments use a
      multidimensional approach. There are specific instruments needed to take account
      of influences on informal caregivers. Moreover, it was shown that several
      aspects, such as crime rates and employment should be considered to estimate the
      impact on societal costs. Finally, the intervention must be described in detail
      and well defined to reduce variability. In conclusion, economic evaluations of
      welfare interventions increase complexity. These must be accounted for to permit
      valid assessments of the value for money of welfare interventions. 

PMID- 25961759
TI  - Smokers With Adequate Vitamin C Intake Show a Preferable Pulmonary Function Test.
AB  - OBJECTIVE: Airflow obstruction often results from the chronic inflammation caused
      by cigarette smoke. It has been concluded that cigarette smoke-induced oxidative
      damage is prevented by ascorbic acid on a cellular level. The purpose of the
      current study was to explore the effect of vitamin C intake on pulmonary function
      in established smokers (100 or more cigarettes) and never-smokers in a Korean
      population. METHODS: The 2974 enrolled men and women over the age of 40 in the
      Korea National Health and Nutrition Examination Survey IV 2008 were divided into
      4 groups based on smoking patterns (never-smoker vs established smoker) and
      vitamin C intake from dietary assessment (higher vs lower; median value: 77.18
      mg/day). RESULTS: Univariate analysis showed associations between forced
      expiratory volume in 1 second (FEV1), FEV/forced vital capacity (FVC) and age,
      gender, body mass index (BMI), pack-years, vitamin C intake, and additional
      micronutrient intake. On multiple logistic regression analysis, the odds ratios
      (95% confidence interval) for FEV1 < 80% predicted were 1.000 (never-smokers,
      higher vitamin C intake), 1.067 (0.823, 1.383; never-smokers, lower vitamin C
      intake), 1.224 (0.871, 1.721; established smokers, higher vitamin C intake), and
      1.479 (1.057, 2.072; established smokers, lower vitamin C intake). The odds
      ratios for FEV1/FVC < 0.70 were 1.177 (0.821, 1.687; never-smokers, lower vitamin
      C intake), 1.637 (1.094, 2.445; established smokers, higher vitamin C intake),
      and 2.093 (1.403, 3.122; established smokers, lower vitamin C intake) after
      adjusting for confounding factors (p < 0.001). CONCLUSIONS: Korean smokers with
      adequate vitamin C intake showed a preferable pulmonary function test.

PMID- 25961760
TI  - Glycopolymers as Antiadhesives of E. coli Strains Inducing Inflammatory Bowel
      Diseases.
AB  - n-Heptyl alpha-d-mannose (HM) is a nanomolar antagonist of FimH, a virulence
      factor of E. coli. Herein we report on the construction of multivalent HM-based
      glycopolymers as potent antiadhesives of type 1 piliated E. coli. We investigate
      glycopolymer/FimH and glycopolymer/bacteria interactions and show that HM-based
      glycopolymers efficiently inhibit bacterial adhesion and disrupt established cell
      bacteria interactions in vitro at very low concentration (0.1 MUM on a mannose
      unit basis). On a valency-corrected basis, HM-based glycopolymers are,
      respectively, 10(2) and 10(6) times more potent than HM and d-mannose for their
      capacity to disrupt the binding of adherent-invasive E. coli to T84 intestinal
      epithelial cells. Finally, we demonstrate that the antiadhesive capacities of HM
      based glycopolymers are preserved ex vivo in the colonic loop of a transgenic
      mouse model of Crohn's disease. All together, these results underline the
      promising scope of HM-based macromolecular ligands for the antiadhesive treatment
      of E. coli induced inflammatory bowel diseases. 

PMID- 25961761
TI  - Biosignal Interpretation II. Advanced Methods for Studying Biosignals and Images.

PMID- 25961758
TI  - Work-family conflict, cardiometabolic risk, and sleep duration in nursing
      employees.
AB  - We investigated associations of work-family conflict and work and family
      conditions with objectively measured cardiometabolic risk and sleep. Multilevel
      analyses assessed cross-sectional associations between employee and job
      characteristics and health in analyses of 1,524 employees in 30 extended-care
      facilities in a single company. We examined work and family conditions in
      relation to: (a) validated, cardiometabolic risk score based on measured blood
      pressure, cholesterol, glycosylated hemoglobin, body mass index, and self
      reported tobacco consumption and (b) wrist actigraphy-based sleep duration. In
      fully adjusted multilevel models, work-to-family conflict but not family-to-work
      conflict was positively associated with cardiometabolic risk. Having a lower
      level occupation (nursing assistant vs. nurse) was associated with increased
      cardiometabolic risk, whereas being married and having younger children at home
      was protective. A significant Age * Work-to-Family Conflict interaction revealed
      that higher work-to-family conflict was more strongly associated with increased
      cardiometabolic risk in younger employees. High family-to-work conflict was
      significantly associated with shorter sleep duration. Working long hours and
      having children at home were both independently associated with shorter sleep
      duration. High work-to-family conflict was associated with longer sleep duration.
      These results indicate that different dimensions of work-family conflict may pose
      threats to cardiometabolic health and sleep duration for employees. This study
      contributes to the research on work-family conflict, suggesting that work-to
      family and family-to-work conflict are associated with specific health outcomes.
      Translating theory and findings to preventive interventions entails recognition
      of the dimensionality of work and family dynamics and the need to target specific
      work and family conditions.

PMID- 25961762
TI  - Nanotextured polymer substrates show enhanced cancer cell isolation and cell
      culture.
AB  - Detection of circulating tumor cells (CTCs) in the early stages of cancer is a
      great challenge because of their exceedingly small concentration. There are only
      a few approaches sensitive enough to differentiate tumor cells from the plethora
      of other cells in a sample like blood. In order to detect CTCs, several
      antibodies and aptamers have already shown high affinity. Nanotexture can be used
      to mimic basement membrane to further enhance this affinity. This article reports
      an approach to fabricate nanotextured polydimethylsiloxane (PDMS) substrates
      using micro reactive ion etching (micro-RIE). Three recipes were used to prepare
      nanotextured PDMS using oxygen and carbon tetrafluoride. Micro-RIE provided
      better control on surface properties. Nanotexturing improved the affinity of PDMS
      surfaces to capture cancer cells using surface immobilized aptamers against cell
      membrane overexpressed with epidermal growth factor receptors. In all cases,
      nanotexture of PDMS increased the effective surface area by creating nanoscale
      roughness on the surface. Nanotexture also enhanced the growth rate of cultured
      cells compared to plain surfaces. A comparison among the three nanotextured
      surfaces demonstrated an almost linear relationship between the surface roughness
      and density of captured tumor cells. The nanotextured PDMS mimicked biophysical
      environments for cells to grow faster. This can have many implications in
      microfluidic platforms used for cell handling. 

PMID- 25961763
TI  - Stereotactic Microanatomy of the Nucleus Accumbens Stimulation for Obsessive
      Compulsive Disorder: Reported Coordinates and Mavridis' Area.

PMID- 25961764
TI  - Identification of Novel Polyfluorinated Ether Sulfonates as PFOS Alternatives in
      Municipal Sewage Sludge in China.
AB  - A 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFAES) with the trade
      name F-53B, is an alternative to perfluorooctanesulfonate (PFOS) in
      electroplating industry that is uniquely used in China. It was developed as a
      mist suppressant initially in the 1970s, but the environmental behaviors and
      potential adverse effects of the 6:2 Cl-PFAES have only recently been
      investigated. In this work, the occurrence and distribution of perfluoroalkyl
      sulfonate (PFSA), fluorotelomer sulfonate (FTSA), and PFAES analogues were
      investigated in municipal sewage sludge samples collected around China.
      Perfluorobutane, perfluorohexane, perfluorooctane, and perfluorodecanesulfonates,
      6:2 and 8:2 FTSAs, and the emerging 6:2 Cl-PFAES were detected. Moreover, 8:2 and
      10:2 Cl-PFAESs were identified for the first time as new polyfluorinated
      contaminants using high resolution mass spectrometry. These fluorinated analytes
      were further quantified with the aid of commercial and laboratory-purified
      standards. PFOS was the predominant contaminant with a geometric mean (GM) value
      of 3.19 ng/g dry weight (d.w.), which was subsequently followed by 6:2 Cl-PFAES
      and 8:2 Cl-PFAES (GM: 2.15 and 0.50 ng/g d.w., respectively). Both 6:2 and 8:2 Cl
      PFAES were positively detected as the major components in the F-53B commercial
      product, and discrete 6:2 Cl-PFAES/8:2 Cl-PFAES ratios in the product and sludge
      samples might suggest 8:2 Cl-PFAES had enhanced sorption behavior in the sludge
      due to the increase in hydrophobicity. 

PMID- 25961765
TI  - High-dose therapy and autologous stem cell transplant in older adults with
      multiple myeloma.
AB  - Randomized trials showing that high-dose therapy with autologous stem cell
      transplant (ASCT) improved the overall survival (OS) in multiple myeloma (MM)
      excluded patients over age 65. To compare the outcomes of older adults with MM
      who underwent ASCT with non-transplant strategies, we identified 146 patients
      aged 65-77 with newly diagnosed MM seen in the Washington University School of
      Medicine from 2000 to 2010. Survival among patients who did (N=62) versus did not
      (N=84) undergo ASCT was compared using Cox proportional hazards modeling,
      controlling for comorbidities, Eastern Cooperative Oncology Group performance
      status (PS) and the propensity to undergo ASCT. Median age was 68 years (range 65
      77). PS and comorbidities did not differ significantly between those who did
      versus those who did not undergo ASCT. Median OS was significantly longer in
      patients who underwent ASCT than in those who did not (median 56.0 months (95%
      confidence intervals (CIs) 49.1-65.4) versus 33.1 months (24.3-43.1), P=0.004).
      Adjusting for PS, comorbidities, Durie-Salmon stage and the propensity to undergo
      ASCT, ASCT was associated with superior OS (HR for mortality 0.52 (95% CI 0.30
      0.91), P=0.02). In a cohort of older adults with MM, undergoing ASCT was
      associated with a nearly 50% lower mortality, after controlling for PS,
      comorbidities, stage and the propensity to undergo ASCT. 

PMID- 25961766
TI  - Fecal calprotectin and alpha1-antitrypsin dynamics in gastrointestinal GvHD.
AB  - In a previous study, the fecal biomarkers calprotectin and alpha1-antitrypsin
      (alpha1-AT) at symptom onset were reported to be significantly associated with
      the response to steroids in gastrointestinal GvHD (GI-GvHD). The purpose of this
      trial was to evaluate the dynamics of the fecal biomarkers calprotectin and
      alpha1-AT throughout the course of GvHD. Patients who were refractory to steroids
      had initially higher biomarker levels and in the course of GvHD demonstrated a
      continuous increase in fecal biomarkers. In contrast, the dynamics of
      calprotectin and alpha1-AT demonstrated low and decreasing levels in cortico
      sensitive GvHD. In steroid-refractory patients who received a second line of
      treatment, the biomarker levels at the beginning of second-line treatment did not
      predict the subsequent response. Nevertheless, calprotectin levels progressively
      decreased in subsequent responders, whereas non-responders demonstrated
      continuously high levels of calprotectin. alpha1-AT values correlated to a lesser
      extent with the response to second-line treatment and remained elevated in both
      non-responders and responders. In conclusion, calprotectin monitoring can be of
      use in the management of immunosuppressive treatment in GI-GvHD. 

PMID- 25961767
TI  - A randomized control trial of a psychosocial intervention for caregivers of
      allogeneic hematopoietic stem cell transplant patients: effects on distress.
AB  - Caregivers of patients receiving allogeneic hematopoietic stem cell transplants
      (allo-HSCT) serve a pivotal role in patient care but experience high stress,
      anxiety and depression as a result. We theorized that stress management adapted
      for allo-HSCT caregivers would reduce distress compared with treatment as usual
      (TAU). Of 267 consecutive caregivers of allo-HSCT patients approached, 148
      (mean=53.5 years, 75.7% female) were randomized to either psychosocial
      intervention (i=74) or TAU (n=74). Eight one-on-one stress management sessions
      delivered across the 100-day post-transplant period focused on understanding
      stress, changing role(s) as caregiver, cognitive behavioral stress management,
      pacing respiration and identifying social support. Primary outcomes included
      perceived stress (psychological) and salivary cortisol awakening response (CAR)
      (physiological). Randomized groups were not statistically different at baseline.
      Mixed models analysis of covariance (intent-to-treat) showed that intervention
      was associated with significantly lower caregiver stress 3 months post transplant
      (mean=20.0, 95% confidence interval (95% CI)=17.9-22.0) compared with TAU
      (mean=23.0, 95% CI=21.0-25.0) with an effect size (ES) of 0.39 (P=0.039).
      Secondary psychological outcomes, including depression and anxiety, were
      significantly reduced with ESs of 0.46 and 0.66, respectively. Caregiver CAR did
      not differ from non-caregiving controls at baseline and was unchanged by
      intervention. Despite significant caregiving burden, this psychosocial
      intervention significantly mitigated distress in allo-HSCT caregivers. 

PMID- 25961768
TI  - Mannan-binding lectin deficiency attenuates acute GvHD in pediatric hematopoietic
      stem cell transplantation.

PMID- 25961769
TI  - Extensive bone marrow necrosis resolved by allogeneic umbilical cord blood
      mesenchymal stem cell transplantation in a chronic myeloid leukemia patient.

PMID- 25961771
TI  - Cutaneous macrophage infiltration in acute GvHD.

PMID- 25961770
TI  - Long-term outcome of HLA-haploidentical hematopoietic stem cell transplantation
      without in vitro T-cell depletion based on an FBCA conditioning regimen for
      hematologic malignancies.
AB  - Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an
      alternative for patients who need a transplant without having conventional
      donors. One hundred and five consecutive patients with hematologic malignancies
      who underwent G-CSF-primed peripheral blood haplo-HSCT without in vitro T-cell
      depletion in our single center were reported in this study. Patients were
      categorized into the intermediate-risk group (n=28) or high-risk group (n=77)
      according to the risk stratification. The conditioning regimen included
      fludarabine, busulfan, cyclophosphamide and anti-lymphocyte globulin. The
      cumulative incidence of grades II-IV acute GvHD (aGvHD) on day +100 was 21.9%,
      and that of grades III-IV aGvHD was 14.3%. The 2-year cumulative incidence of
      total chronic GvHD (cGvHD) was 24.1%, and that of extensive cGvHD was 5.6% in 83
      eligible patients. The 3-year cumulative incidence rates of relapse and no
      relapse mortality were 21.9% and 30.5%, respectively. After a median follow-up of
      35 months, the 3-year probabilities of overall and disease-free survival for the
      intermediate-risk and high-risk groups were 63.2% and 39.8% and 61.2% and 32.2%,
      respectively. In multivariate analysis, the outcome of survival (overall survival
      and disease-free survival) was associated with the risk stratification, disease
      status at transplant and dose of infused mononuclear cells. Our results suggest
      that unmanipulated peripheral blood stem cell allograft performed with
      fludarabine, busulfan, cyclophosphamide and anti-lymphocyte globulin conditioning
      regimen is feasible. 

PMID- 25961772
TI  - Prognostic understanding, quality of life and mood in patients undergoing
      hematopoietic stem cell transplantation.
AB  - Little is known about how patients undergoing hematopoietic stem cell
      transplantation (HCT) and their family caregivers (FC) perceive their prognosis.
      We examined prognostic understanding in patients undergoing HCT and their FC and
      its relationship with quality of life (QOL) and mood. We conducted a longitudinal
      study of patients (and FC) hospitalized for HCT. We used a questionnaire to
      measure participants' prognostic understanding and asked the oncologists to
      estimate patients' prognosis prior to HCT. We assessed QOL and mood weekly and
      evaluated the relationship between prognostic understanding, and QOL and mood
      using multivariable linear mixed models. We enrolled 90 patients undergoing
      (autologous (n=30), myeloablative (n=30) or reduced intensity allogeneic (n=30))
      HCT. About 88.9% of patients and 87.1% of FC reported it is 'extremely' or 'very'
      important to know about prognosis. However, 77.6% of patients and 71.7% of FC
      reported a discordance and more optimistic prognostic perception compared to the
      oncologist (P<0.0001). Patients with a concordant prognostic understanding with
      their oncologists reported worse QOL (beta=-9.4, P=0.01) and greater depression
      at baseline (beta=1.7, P=0.02) and over time ((beta=1.2, P<0.0001). Therefore,
      Interventions are needed to improve prognostic understanding, while providing
      patients with adequate psychological support. 

PMID- 25961773
TI  - Ovarian tissue cryopreservation in girls undergoing haematopoietic stem cell
      transplant: experience of a single centre.
AB  - Fertility after childhood haemopoietic stem cell transplant (HSCT) is a major
      concern. Conditioning regimens before HSCT present a high risk (>80%) of ovarian
      failure. Since 2000, we have proposed cryopreservation of ovarian tissue to
      female patients undergoing HSCT at our centre, to preserve future fertility.
      After clinical and haematological evaluation, the patients underwent ovarian
      tissue collection by laparoscopy. The tissue was analysed by histologic
      examination to detect any tumour contamination and then frozen following the slow
      freezing procedure and cryopreserved in liquid nitrogen. From August 2000 to
      September 2013, 47 patients planned to receive HSCT, underwent ovarian tissue
      cryopreservation. The median age at diagnosis was 11.1 years and at the time of
      procedure it was 13 years, respectively. Twenty-four patients were not pubertal
      at the time of storage, whereas 23 patients had already experienced menarche. The
      median time between laparoscopy and HSCT was 25 days. Twenty-six out of 28
      evaluable patients (93%) developed hypergonadotropic hypogonadism at a median
      time of 23.3 months after HSCT. One patient required autologous orthotopic
      transplantation that resulted in one live birth. Results show a very high rate of
      iatrogenic hypergonadotropic hypogonadism, highlighting the need for fertility
      preservation in these patients. 

PMID- 25961774
TI  - Chronic GvHD-associated serositis and pericarditis.
AB  - Serositis is a rare manifestation of chronic GvHD (cGvHD). No risk factors or
      laboratory changes associated with this syndrome have been recognized to date,
      and outcomes have not been described in a large series. We searched our
      institutional database for patients undergoing allogeneic hematopoietic cell
      transplant identified as having serositis or pericarditis. Laboratory studies
      from prior to diagnosis, at diagnosis and post diagnosis of serositis, as well as
      outcomes from invasive procedures were included. Twenty patients met criteria for
      cGvHD-associated serositis, and all but three patients had a prior diagnosis of
      cGvHD. Fifteen were male, and the complication occurred in the setting of
      immunosuppressant taper in 12 cases. Ten patients required invasive
      interventions, including pericardial window or stripping. A significant increase
      in blood monocytes and decrease in serum albumin were identified at diagnosis
      compared with pre-diagnosis. Out of 20 patients, 17 were treated with steroids,
      with 12 demonstrating a complete response. These data suggest that cGvHD
      associated serositis occurs mainly in the setting of treated as opposed to de
      novo cGvHD and biomarkers associated with the syndrome include a decrease in
      albumin and an increase in absolute monocyte count. Outcome data from larger
      series are required to better understand the optimal management of this rare
      complication. 

PMID- 25961776
TI  - Publications of bone marrow transplants in Latin America. A report of the Latin
      American Group of Bone Marrow Transplantation.

PMID- 25961775
TI  - Risk factors and timing of relapse after allogeneic transplantation in pediatric
      ALL: for whom and when should interventions be tested?
AB  - We previously showed that minimal residual disease (MRD) detection pre
      hematopoietic cell transplant (HCT) and acute GvHD (aGvHD) independently
      predicted risk of relapse in pediatric ALL. In this study we further define risk
      by assessing timing of relapse and the effects of leukemia risk category and post
      HCT MRD. By multivariate analysis, pre-HCT MRD <0.1% and aGvHD by day +55 were
      associated with decreased relapse and improved event-free survival (EFS).
      Intermediate leukemia risk status predicted decreased relapse, and improved EFS
      and overall survival (OS). Patients with pre-HCT MRD ?0.1% who did not develop
      aGvHD compared with those with MRD <0.1% who did develop aGvHD had much worse
      survival (2 years EFS 18% vs 71%; P=0.001, 2 years OS 46 vs 74%; P=0.04).
      Patients with pre-HCT MRD <0.1% who did not experience aGvHD had higher rates of
      relapse than those who did develop aGvHD (40% vs 13%; P= 0.008). Post-HCT MRD led
      to a substantial increase in relapse risk (HR=4.5, P<0.01). Patients at high risk
      of relapse can be defined after transplant using leukemia risk category, presence
      of MRD pre or post HCT, and occurrence of aGvHD. An optimal window to initiate
      intervention to prevent relapse occurs between day +55 and +200 after HCT. 

PMID- 25961777
TI  - Engineering haploidentical transplants.

PMID- 25961779
TI  - Rare Anterior Segment Retinoblastoma Masquerading as Corneal Endotheliitis.
AB  - We present a unique case involving a 6-year-old female with a unilateral corneal
      endotheliitis-like finding, who was ultimately found to have a form of anterior
      diffuse infiltrating retinoblastoma with no evidence of retinal involvement. The
      patient's presumed endotheliitis was initially treated with topical dexamethasone
      and oral acyclovir without improvement. She then underwent multiple fine-needle
      aspirations of anterior chamber fluid, which were negative for abnormal findings
      of viral polymerase chain reaction, viral cultures, and flow cytometry. Months
      after initial presentation, an anterior chamber angle mass developed and a biopsy
      identified retinoblastoma cells. The patient underwent plaque radiotherapy of the
      cornea and systemic chemotherapy. The patient regained good vision and is tumor
      free at 13 months. Anterior inflammation is a rare form of masquerade syndrome
      associated with retinoblastoma; however, it tends to be associated with diffuse
      posterior segment retinoblastoma when it does occur. Diffuse anterior
      retinoblastoma is a rare form of retinoblastoma with no apparent focus in the
      retina. Ultimately, our patient developed an anterior chamber angle lesion, which
      was biopsied and proven to be retinoblastoma. Unusual corneal endotheliitis-like
      findings in children that are not responsive to conventional treatment should
      raise the clinician's suspicion of malignancy, even when no retinal lesion is
      detected. 

PMID- 25961778
TI  - Mutation in TET2 or TP53 predicts poor survival in patients with myelodysplastic
      syndrome receiving hypomethylating treatment or stem cell transplantation.

PMID- 25961780
TI  - Nanoscale Swelling Heterogeneities in Type I Collagen Fibrils.
AB  - The distribution of water within the supramolecular structure of collagen fibrils
      is important for understanding their mechanical properties as well as the
      biomineralization processes in collagen-based tissues. We study the influence of
      water on the shape and the mechanical properties of reconstituted fibrils of type
      I collagen on the nanometer scale. Fibrils adsorbed on a silicon substrate were
      imaged with multiset point intermittent contact (MUSIC)-mode atomic force
      microscopy (AFM) in air at 28% relative humidity (RH) and in a hydrated state at
      78% RH. Our data reveal the differences in the water uptake between the gap and
      overlap regions during swelling. This provides direct evidence for different
      amounts of bound and free water within the gap and overlap regions. In the dry
      state, the characteristic D-band pattern visible in AFM images is due to height
      corrugations along a fibril's axis. In the hydrated state, the fibril's surface
      is smooth and the D-band pattern reflects the different mechanical properties of
      the gap and overlap regions. 

PMID- 25961781
TI  - Assessment of the Efficacy and Safety of BMS-820836 in Patients With Treatment
      Resistant Major Depression: Results From 2 Randomized, Double-Blind Studies.
AB  - Two phase 2B, randomized, double-blind studies assessed the efficacy and safety
      of fixed or flexible dose of triple monoamine uptake inhibitor BMS-820836 in
      patients with treatment-resistant depression to demonstrate whether switching to
      BMS-820836 was superior to the continuation of standard antidepressant treatment.
      Patients with a history of inadequate response to 1 to 3 adequate trials of
      antidepressant therapies were prospectively treated with duloxetine 60 mg/d for 8
      weeks (CN162-006) or duloxetine 60 mg/d or escitalopram 20 mg/d for 7 weeks
      (CN162-007). Inadequate responders were randomized to continue their prospective
      phase treatment or switch to flexible-dose (0.5-2 mg/d; CN162-006) or fixed-dose
      (0.25, 0.5, 1, or 2 mg/d; CN162-007) BMS-820836 for 6 weeks. The primary end
      point in both studies was mean change in Montgomery-Asberg Depression Rating
      Scale (MADRS) total score from randomization to study end point. BMS-820836
      flexible (0.5-2 mg/d) or fixed dose of 1 mg/d or greater showed efficacy similar
      to the continuation of antidepressant treatment, with no statistically
      significant or clinically meaningful differences. In the CN162-006 study, the
      adjusted mean (SE) change in MADRS total score was -8.7 (0.661) and -8.1 (0.656)
      for BMS-820836 and duloxetine, respectively (P = 0.526). In the CN162-007 study,
      the adjusted mean (SE) change in MADRS total score was -7.3 (0.830) and -6.6
      (0.842) for BMS-820836 of 1 and 2 mg, respectively, and -6.9 (0.602) for the
      continuation group (P = 0.910). Thus, BMS-820836 was well tolerated, with no
      evidence of dose-dependent discontinuations due to adverse events, but it failed
      to demonstrate superiority to the continuation of an existing antidepressant in
      patients with treatment-resistant depression. 

PMID- 25961782
TI  - Phosphorylation-Mediated Assembly of a Semisynthetic Fluorescent Protein for
      Label-Free Detection of Protein Kinase Activity.
AB  - Protein phosphorylation catalyzed by protein kinases plays a critical role in
      many intracellular processes, and detecting kinase activity is important in
      biochemical research and drug discovery. Herein, we developed a novel fluorescent
      biosensor to detect protein kinase activity based on phosphorylation-mediated
      assembly of semisynthetic green fluorescent protein (GFP). A chimaera S-peptide
      composed of the 10th beta-strand of GFP (s10) and a kinase substrate peptide was
      synthesized. Kinase-catalyzed phosphorylation of the S-peptide can protect its
      s10 part against cleavage by carboxypeptidase Y (CPY). Then, the peptide can bind
      the truncated GFP (tGFP, GFP without s10) to assemble intact GFP and recover
      fluorescence. Unphosphorylated S-peptide would be degraded by CPY, and
      fluorescent protein assembly could not occur. Thus, the kinase-catalyzed
      phosphorylation can switch on the fluorescence signal. This platform has been
      successfully applied to detect the activity of cAMP-dependent protein kinase with
      a low detection limit of 0.50 mU/MUL and its inhibition of H-89 with an IC50
      value of 23.4 nM. The feasibility of this method has been further demonstrated by
      assessment of the kinase activity and inhibition in the cell lysate. Moreover,
      based on the reverse principle, this method was expanded to detect the activity
      of protein phosphatase 1. Our method, using semisynthetic GFP as a readout, is
      facile, sensitive, label-free, and highly versatile, thus showing great potential
      as a promising platform for protein kinase detection and inhibitor screening. 

PMID- 25961783
TI  - Application of Thio-Ugi Adducts for the Preparation of Benzo[b]thiophene and S
      Heterocycle Library via Copper Catalyzed Intramolecular C-S Bond Formation.
AB  - Fused heterocycles, such as benzo[b]thiophene, thiochroman,
      benzo[b][1,4]thiazine, and 1,4-benzothiazepine were generated from thio-Ugi
      adducts containing a thioamide group through copper-catalyzed intramolecular C-S
      bond formation under microwave irradiation. 

PMID- 25961784
TI  - Light-Controlled Conductance Switching in Azobenzene-Containing MWCNT-Polymer
      Nanocomposites.
AB  - We report on reversible light-controlled conductance switching in devices
      consisting of multiwalled carbon nanotube (MWCNT)-polymer nanocomposites blended
      with azobenzene molecules and photoisomerization of the latter. Both the
      azobenzene molecules and MWCNT, which are functionalized with carboxyl groups
      (MWCNT-COOH), are embedded independently in a poly(methyl methacrylate) matrix,
      and thin films are prepared by using a simple spin-coating technique. We
      demonstrate the feasibility of the present concept with a photocurrent switching
      amplitude of almost 10%. 

PMID- 25961785
TI  - Diabetes registries in patient-centered medical homes.
AB  - BACKGROUND: Little is known about the effectiveness of a patient registry, an
      attribute within the patient-centered medical home (PCMH) model, as it relates to
      diabetes health outcomes. The purpose of this retrospective study was to compare
      hemoglobin A1c (HbA1c) values for patients (n = 713) from clinics with an
      established diabetes registry (n = 7) to patients (n = 325) at clinics without a
      diabetes registry (n = 15), and determine whether HbA1c levels improve
      significantly more over time at registry clinics compared to nonregistry clinics.
      METHODS: Up to 3 most recent sequential HbA1c values, along with demographic
      variables of age, body mass index (BMI), gender, race, insurance type, marital
      status, and whether or not the patient lived in the local area around the medical
      center were extracted from the electronic medical record used throughout the
      primary health care system. Presence of comorbid conditions of lipid metabolism
      and hypertension disorders were also collected. Analysis of variance and
      propensity-score-matched 2-sample analyses were used to examine the association
      between diabetes registry status HbA1c, controlling for demographic variables.
      RESULTS: Analyses indicated no evidence that patients in clinics with established
      diabetes registries had improved HbA1c levels significantly more than patients in
      clinics without diabetes registries. DISCUSSION: Patients in clinics with
      diabetes registry did not have greater overall improvement in HbA1c values than
      patients in nondiabetes registry clinics. However, patients at all clinics had
      significantly reduced HbA1c values over time. More research is needed to
      determine if registries are effective PCMH tools to reduce diabetes morbidity and
      mortality.

PMID- 25961786
TI  - Chronic myelogenous leukemia in eastern Pennsylvania: an assessment of registry
      reporting.
AB  - BACKGROUND: Chronic myelogenous leukemia (CML) has been reportable to the
      Pennsylvania Cancer Registry (PCR) since the 1980s, but the completeness of
      reporting is unknown. This study assessed CML reporting in eastern Pennsylvania
      where a cluster of another myeloproliferative neoplasm was previously identified.
      METHODS: Cases were identified from 2 sources: 1) PCR case reports for residents
      of Carbon, Luzerne, or Schuylkill County with International Classification of
      Diseases for Oncology, Third Edition (ICD-O-3) codes 9875 (CML, BCR-ABL+), 9863
      (CML, NOS), and 9860 (myeloid leukemia) and date of diagnosis 2001-2009, and 2)
      review of billing records at hematology practices. Participants were interviewed
      and their medical records were reviewed by board-certified hematologists.
      RESULTS: PCR reports included 99 cases coded 9875 or 9863 and 9 cases coded 9860;
      2 additional cases were identified by review of billing records. Of the 110
      identified cases, 93 were mailed consent forms, 23 consented, and 12 medical
      records were reviewed. Hematologists confirmed 11 of 12 reviewed cases as CML
      cases; all 11 confirmed cases were BCR/ABL positive, but only 1 was coded as
      positive (code 9875). CONCLUSIONS: Very few unreported CML cases were identified,
      suggesting relatively complete reporting to the PCR. Cases reviewed were
      accurately diagnosed, but ICD-0-3 coding often did not reflect BCR-ABL-positive
      tests. Cancer registry abstracters should look for these test results and code
      accordingly.

PMID- 25961787
TI  - Acute myocardial infarction in pregnancy: a statewide analysis.
AB  - OBJECTIVE: Acute myocardial infarction (AMI) during pregnancy and the puerperium
      is a rare but devastating event. The objective of this study was to describe the
      clinical and epidemiological features of pregnancy-related AMI. METHODS: A
      retrospective study was conducted using Texas hospital inpatient data (years 2004
      2007). Diagnoses and procedures had been coded using International Classification
      of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). Adjusted odds
      ratios (OR) for hospital mortality and length of stay >4 days (prolonged length
      of stay [PLOS]) were calculated using logistic regression with Firth's bias
      correction and multiple imputation. RESULTS: 103 women with pregnancy-related AMI
      were identified in the statewide hospital database (6.5 cases per 100,000
      births). The prevalence of cardiomyopathy was 16.5%. Approximately 14% of the
      pregnancies were complicated by preeclampsia/eclampsia. A history of cocaine use
      was noted in 3 patients. Congestive heart failure was present in 18 patients
      (17.5%). Two patients had attempted suicide and 1 died in the hospital. The
      overall hospital mortality rate was 9.7%. Placement of coronary artery stents was
      the most common coronary revascularization procedure (11 patients or 10.7%). The
      adjusted hospital mortality OR for women 35-39 years old (versus 30-34 years old)
      was 6.29 (P = .07). Patients with preeclampsia were more likely to have PLOS than
      patients whose deliveries were not complicated by preeclampsia (OR, 3.84; P =
      .06). CONCLUSIONS: While AMI in pregnancy remains a rare occurrence, it is
      associated with significant morbidity and a high case-fatality rate.

PMID- 25961788
TI  - How we organized a regional meeting: cancer registrars association of central
      Ohio and Michigan Cancer Registrars Association.
AB  - Due to the cost of sending staff to a national meeting, it is sometimes difficult
      for hospitals to fulfill Cancer Program Standard 1.11 if they desire a
      commendation. The Cancer Registrars Association of Central Ohio teamed up with
      the Michigan Cancer Registrars Association to organize a regional meeting. The
      goal for the planning committee was to keep costs to a minimum. The meeting was a
      success with nearly 190 attendees from 5 states. 

PMID- 25961789
TI  - Larynx carcinoma regulates tumor-associated macrophages through PLGF signaling.
AB  - Cancer neovascularization plays an essential role in the metastasis of larynx
      carcinoma (LC). However, the underlying molecular mechanisms are not completely
      understood. Recently, we reported that placental growth factor (PLGF) regulates
      expression of matrix metalloproteinase 3 (MMP3) through ERK/MAPK signaling
      pathway in LC. Here, we show that MMP9 upregulated in LC, and appeared to be
      mainly produced by M2 macrophages (tumor-associated macrophages (TAM)). In a
      transwell co-culture system, PLGF secreted by LC cells triggered macrophage
      polarization to a TAM subtype that releases MMP9. Moreover, MMP9 was found to be
      activated in the PLGF-polarized TAM via transforming growth factor beta (TGFbeta)
      receptor signaling activation. Furthermore, PLGF in LC cells induced macrophage
      polarization in vivo, and significantly promoted the growth of LC. Thus, together
      with our previous work, our study highlights a pivotal role of cross-talk between
      TAM and LC in regulating the metastasis of LC. 

PMID- 25961790
TI  - Function and developmental origin of a mesocortical inhibitory circuit.
AB  - Midbrain ventral tegmental neurons project to the prefrontal cortex and modulate
      cognitive functions. Using viral tracing, optogenetics and electrophysiology, we
      found that mesocortical neurons in the mouse ventrotegmental area provide fast
      glutamatergic excitation of GABAergic interneurons in the prefrontal cortex and
      inhibit prefrontal cortical pyramidal neurons in a robust and reliable manner.
      These mesocortical neurons were derived from a subset of dopaminergic
      progenitors, which were dependent on prolonged Sonic Hedgehog signaling for their
      induction. Loss of these progenitors resulted in the loss of the mesocortical
      inhibitory circuit and an increase in perseverative behavior, whereas mesolimbic
      and mesostriatal dopaminergic projections, as well as impulsivity and attentional
      function, were largely spared. Thus, we identified a previously uncharacterized
      mesocortical circuit contributing to perseverative behaviors and found that the
      diversity of dopaminergic neurons begins to be established during their
      progenitor phase. 

PMID- 25961793
TI  - In Situ Determination of Tacticity, Deactivation, and Kinetics in [rac-(C2H4(1
      Indenyl)2)ZrMe][B(C6F5)4] and [Cp2ZrMe][B(C6F5)4]-Catalyzed Polymerization of 1
      Hexene Using (13)C Hyperpolarized NMR.
AB  - The stereochemistry, kinetics, and mechanism of olefin polymerization catalyzed
      by a set of zirconium-based metallocenes was studied by NMR using dissolution
      dynamic nuclear polarization (DNP). Hyperpolarized 1-hexene was polymerized in
      situ with a C2 symmetric catalyst, [(EBI)ZrMe][B(C6F5)4] (EBI = rac-(C2H4(1
      indenyl)2)), and a C2v symmetric catalyst, [(Cp)2ZrMe][B(C6F5)4] (Cp =
      cyclopentadienyl). Hyperpolarized (13)C NMR spectra were used to characterize
      product tacticity following initiation of the reaction. At the same time, a
      signal gain of 3 orders of magnitude from (13)C hyperpolarization enabled the
      real time observation of catalyst-polymeryl species and deactivation products,
      such as vinylidene and a Zr-allyl complex. The compounds appearing in the
      reaction provide evidence for the existence of beta-hydride elimination and
      formation of a dormant site via a methane-generating mechanism. The presence of a
      deactivating mechanism was incorporated in a model used to determine kinetic
      parameters of the reaction. On this basis, rate constants were measured between
      0.8 and 6.7 mol % of catalyst. The concentration dependence of the rate constants
      obtained indicates a second-order process for polymerization concomitant with a
      first-order process for deactivation. The simultaneous observation of both
      processes in the time evolution of (13)C NMR signals over the course of several
      seconds underlines the utility of hyperpolarized NMR for quantifying early events
      in polymerization reactions. 

PMID- 25961791
TI  - A transcriptional reporter of intracellular Ca(2+) in Drosophila.
AB  - Intracellular Ca(2+) is a widely used neuronal activity indicator. Here we
      describe a transcriptional reporter of intracellular Ca(2+) (TRIC) in Drosophila
      that uses a binary expression system to report Ca(2+)-dependent interactions
      between calmodulin and its target peptide. We found that in vitro assays
      predicted in vivo properties of TRIC and that TRIC signals in sensory systems
      depend on neuronal activity. TRIC was able to quantitatively monitor neuronal
      responses that changed slowly, such as those of neuropeptide F-expressing neurons
      to sexual deprivation and neuroendocrine pars intercerebralis cells to food and
      arousal. Furthermore, TRIC-induced expression of a neuronal silencer in nutrient
      activated cells enhanced stress resistance, providing a proof of principle that
      TRIC can be used for circuit manipulation. Thus, TRIC facilitates the monitoring
      and manipulation of neuronal activity, especially those reflecting slow changes
      in physiological states that are poorly captured by existing methods. TRIC's
      modular design should enable optimization and adaptation to other organisms. 

PMID- 25961794
TI  - Asymmetric synthesis and biological evaluation of natural or bioinspired
      cytotoxic C2-symmetrical lipids with two terminal chiral alkynylcarbinol
      pharmacophores.
AB  - Bidirectional syntheses of C2-symmetrical lipids embedding two terminal
      alkynylcarbinol pharmacophores are reported. Naturally occurring chiral
      alkenylalkynylcarbinol units were generated using Pu's procedure for
      enantioselective addition of terminal alkynes to aldehydes, allowing the first
      asymmetric synthesis of (3R,4E,16E,18R)-icosa-4,16-diene-1,19-diyne-3,18-diol,
      isolated from Callyspongia pseudoreticulata. Two synthetic analogues embedding
      the recently uncovered (S)-dialkynylcarbinol pharmacophore were secured using
      Carreira's procedure adapted to ynal substrates. The dramatic effect of the
      carbinol configuration on cytotoxicity was confirmed with submicromolar IC50
      values against HCT116 cells. 

PMID- 25961792
TI  - Regulation of axon regeneration by the RNA repair and splicing pathway.
AB  - Mechanisms governing a neuron's regenerative ability are important but not well
      understood. We identify Rtca (RNA 3'-terminal phosphate cyclase) as an inhibitor
      of axon regeneration. Removal of Rtca cell-autonomously enhanced axon regrowth in
      the Drosophila CNS, whereas its overexpression reduced axon regeneration in the
      periphery. Rtca along with the RNA ligase Rtcb and its catalyst Archease operate
      in the RNA repair and splicing pathway important for stress-induced mRNA
      splicing, including that of Xbp1, a cellular stress sensor. Drosophila Rtca and
      Archease had opposing effects on Xbp1 splicing, and deficiency of Archease or
      Xbp1 impeded axon regeneration in Drosophila. Moreover, overexpressing mammalian
      Rtca in cultured rodent neurons reduced axonal complexity in vitro, whereas
      reducing its function promoted retinal ganglion cell axon regeneration after
      optic nerve crush in mice. Our study thus links axon regeneration to cellular
      stress and RNA metabolism, revealing new potential therapeutic targets for
      treating nervous system trauma. 

PMID- 25961795
TI  - Nose to Brain Delivery of Midazolam Loaded PLGA Nanoparticles: In Vitro and In
      Vivo Investigations.
AB  - OBJECTIVES: The present study is aimed to develop poly(D, L-lactide-co-glycolic
      acid) (PLGA) nanoparticles (NP) loaded with midazolam (Mdz) for nose to brain
      delivery. MATERIALS AND METHODS: NP were formulated by nanoprecipitation and
      characterized for z-average, zeta potential, % drug entrapment and ex vivo drug
      release. Mdz NP (MNP) were radiolabeled with technetium-99m. Biodistribution and
      gamma scintigraphic studies were performed on Sprague-Dawley rats following
      intranasal (i.n) and intravenous (i.v) administration to trace the transport of
      Mdz for nose-to-brain delivery. RESULTS AND DISCUSSION: MNP showed z-average of
      164+/-4.5nm with polydispersity index 0.099+/-0.02 and zeta potential of -16.6+/
      2.5mV. Ex vivo drug studies indicated that MNP showed 29+/-1.2% of permeation
      upto 4h via sheep nasal mucosa, whereas Mdz suspension (MS) showed drug release
      of 83+/-1.2% within 4h. Comparing i.n administration of MNP, MS and i.v
      administration of MS, scintigraphy imaging and Brain/blood uptake ratios
      indicated higher brain targeting via i.n administration of MNP. CONCLUSION:
      Results indicated that the i.n MNP could be employed as a non invasive mode of
      delivery system with improved drug entrapment, stability and controlled drug
      release over a period of time.

PMID- 25961796
TI  - Dual Drug Conjugate Loaded Nanoparticles for the Treatment of Cancer.
AB  - Two antineoplastic agents, Imatinib (IM) and 5-Fluorouracil (FU) were conjugated
      by hydrolysable linkers through an amide bond and entrapped in polymeric Human
      Serum Albumin (HSA) nanoparticles. The presence of dual drugs in a common carrier
      has the advantage of reaching the site of action simultaneously and acting at
      different phases of the cell cycle to arrest the growth of cancer cells before
      they develop chemoresistance. The study has demonstrated an enhanced anticancer
      activity of the conjugate, and conjugate loaded stealth HSA nanoparticles (NPs)
      in comparison to the free drug in A-549 human lung carcinoma cell line and Zebra
      fish embryos (Danio rerio). Hydrolysability of the conjugate has also been
      demonstrated with complete hydrolysis being observed after 12 h. In vivo
      pharmacodynamics study in terms of tumor volume and pharmacokinetics in mice for
      conjugate (IM-SC-FU) and conjugate loaded nanoparticles showed significant anti
      cancer activity. The other parameters evaluated were particle size (86nm), Poly
      Dispersive Index (PDI) (0.209), zeta potential (-49mV), drug entrapment
      efficiency (96.73%) and drug loading efficiency (89%). Being in stealth mode
      gives the potential for the NPs to evade Reticulo-Endothelial system (RES),
      achieve passive targeting by Enhanced Permeation Retention (EPR) effect with
      controlled release of the therapeutic agent. As the conjugate cleaves into
      individual drugs in the tumor environment, this promises better suppression of
      cancer chemoresistance by delivering dual drugs with different modes of action at
      the same site, thereby synergistically inhibiting the growth of cancerous tissue.

PMID- 25961797
TI  - Cryptochrome 1 regulates the circadian clock through dynamic interactions with
      the BMAL1 C terminus.
AB  - The molecular circadian clock in mammals is generated from transcriptional
      activation by the bHLH-PAS transcription factor CLOCK-BMAL1 and subsequent
      repression by PERIOD and CRYPTOCHROME (CRY). The mechanism by which CRYs repress
      CLOCK-BMAL1 to close the negative feedback loop and generate 24-h timing is not
      known. Here we show that, in mouse fibroblasts, CRY1 competes for binding with
      coactivators to the intrinsically unstructured C-terminal transactivation domain
      (TAD) of BMAL1 to establish a functional switch between activation and repression
      of CLOCK-BMAL1. TAD mutations that alter affinities for co-regulators affect the
      balance of repression and activation to consequently change the intrinsic
      circadian period or eliminate cycling altogether. Our results suggest that CRY1
      fulfills its role as an essential circadian repressor by sequestering the TAD
      from coactivators, and they highlight regulation of the BMAL1 TAD as a critical
      mechanism for establishing circadian timing. 

PMID- 25961798
TI  - X-ray structures of Drosophila dopamine transporter in complex with nisoxetine
      and reboxetine.
AB  - Most antidepressants elicit their therapeutic benefits through selective blockade
      of Na(+)/Cl(-)-coupled neurotransmitter transporters. Here we report X-ray
      structures of the Drosophila melanogaster dopamine transporter in complexes with
      the polycyclic antidepressants nisoxetine or reboxetine. The inhibitors stabilize
      the transporter in an outward-open conformation by occupying the substrate
      binding site. These structures explain how interactions between the binding
      pocket and substituents on the aromatic rings of antidepressants modulate drug
      transporter selectivity. 

PMID- 25961799
TI  - A dynamic DNA-repair complex observed by correlative single-molecule
      nanomanipulation and fluorescence.
AB  - We characterize in real time the composition and catalytic state of the initial
      Escherichia coli transcription-coupled repair (TCR) machinery by using
      correlative single-molecule methods. TCR initiates when RNA polymerase (RNAP)
      stalled by a lesion is displaced by the Mfd DNA translocase, thus giving repair
      components access to the damage. We previously used DNA nanomanipulation to
      obtain a nanomechanical readout of protein-DNA interactions during TCR
      initiation. Here we correlate this signal with simultaneous single-molecule
      fluorescence imaging of labeled components (RNAP, Mfd or RNA) to monitor the
      composition and localization of the complex. Displacement of stalled RNAP by Mfd
      results in loss of nascent RNA but not of RNAP, which remains associated with Mfd
      as a long-lived complex on the DNA. This complex translocates at ~4 bp/s along
      the DNA, in a manner determined by the orientation of the stalled RNAP on the
      DNA. 

PMID- 25961800
TI  - Leachability of heavy metals from lightweight aggregates made with sewage sludge
      and municipal solid waste incineration fly ash.
AB  - Lightweight aggregate (LWA) production with sewage sludge and municipal solid
      waste incineration (MSWI) fly ash is an effective approach for waste disposal.
      This study investigated the stability of heavy metals in LWA made from sewage
      sludge and MSWI fly ash. Leaching tests were conducted to find out the effects of
      MSWI fly ash/sewage sludge (MSWI FA/SS) ratio, sintering temperature and
      sintering time. It was found that with the increase of MSWI FA/SS ratio, leaching
      rates of all heavy metals firstly decreased and then increased, indicating the
      optimal ratio of MSWI fly ash/sewage sludge was 2:8. With the increase of
      sintering temperature and sintering time, the heavy metal solidifying
      efficiencies were strongly enhanced by crystallization and chemical
      incorporations within the aluminosilicate or silicate frameworks during the
      sintering process. However, taking cost-savings and lower energy consumption into
      account, 1100  degrees C and 8 min were selected as the optimal parameters for
      LWA sample- containing sludge production. Furthermore, heavy metal leaching
      concentrations under these optimal LWA production parameters were found to be in
      the range of China's regulatory requirements. It is concluded that heavy metals
      can be properly stabilized in LWA samples containing sludge and cannot be easily
      released into the environment again to cause secondary pollution. 

PMID- 25961801
TI  - Lung function impact from working in the pre-revolution Libyan quarry industry.
AB  - The purpose of this study was to determine the lung impact from working within
      the Libyan quarry industry, and if the length of work impacted the degree of
      degradation. Eighty three workers from eight silica quarries in the Nafusa
      Mountains of Libya opted to participate. These quarries were working the upper
      cretaceous geological structure. Eighty-five individuals who lived in Gharyan
      City with no affiliation to quarry operations participated as controls.
      Spirometry variables evaluated were Forced Vital Capacity (FVC), Forced
      Expiratory Volume at 1.0 second (FEV1), FVC/FEV1 and Peak Expiratory Flow (PEF).
      Control and exposed groups had no differences in terms of height, weight, or
      smoking status (p = 0.18, 0.20, 0.98, respectively). Prior to adjustment for
      other variables, FVC, FEV1, and PEF are all significantly lower in the exposed
      group (p = 0.003, 0.009, 0.03, respectively). After adjustment for age, height,
      weight, and smoking status, there remain significant differences between the
      control and exposed groups for FVC, FEV1, and PEF. This analysis demonstrated
      that exposure to quarry dust has a detrimental effect on lung function, and that
      pre-revolution Libyan quarry workers were being exposed. This study shows that
      any exposure is harmful, as the reduction in lung function was not significantly
      associated with years of exposure. 

PMID- 25961802
TI  - MULTIDETECTOR-ROW COMPUTED TOMOGRAPHY PATTERNS OF BRONCHOESPHAGEAL ARTERY
      HYPERTROPHY AND SYSTEMIC-TO-PULMONARY FISTULA IN DOGS.
AB  - Anomalies involving arterial branches in the lungs are one of the causes of
      hemoptysis in humans and dogs. Congenital and acquired patterns of
      bronchoesophageal artery hypertrophy have been reported in humans based on CT
      characteristics. The purpose of this retrospective study was to describe
      clinical, echocardiographic, and multidetector computed tomography features of
      bronchoesophageal artery hypertrophy and systemic-to-pulmonary arterial
      communications in a sample of 14 dogs. Two main vascular patterns were identified
      in dogs that resembled congenital and acquired conditions reported in humans.
      Pattern 1 appeared as an aberrant origin of the right bronchoesophageal artery,
      normal origin of the left one, and enlargement of both the bronchial and
      esophageal branches that formed a dense network terminating in a pulmonary artery
      through an orifice. Pattern 2 appeared as a normal origin of both right and left
      bronchoesophageal arteries, with an enlarged and tortuous course along the
      bronchi to the periphery of the lung, where they communicated with subsegmental
      pulmonary arteries. Dogs having Pattern 1 also had paraesophageal and esophageal
      varices, with the latter being confirmed by videoendoscopy examination. Authors
      conclude that dogs with Pattern 1 should be differentiated from dogs with other
      congenital vascular systemic-to-pulmonary connections. Dogs having Pattern 2
      should be evaluated for underlying pleural or pulmonary diseases.
      Bronchoesophageal artery hypertrophy can be accompanied by esophageal venous
      engorgement and should be included in the differential diagnosis for esophageal
      and paraesophageal varices in dogs. 

PMID- 25961803
TI  - Thermoacoustic transduction in individual suspended carbon nanotubes.
AB  - We report an experimental measurement of the acoustic signal emitted from an
      individual suspended carbon nanotube (CNT) approximate 2 MUm in length, 1 nm in
      diameter, and 10(-21) kg in mass. This system represents the smallest
      thermoacoustic system studied to date. By applying an AC voltage of 1.4 V at 8
      kHz to the suspended CNT, we are able to detect the acoustic signal using a
      commercial microphone. The acoustic power detected is found to span a range from
      0.1 to 2.4 attoWatts or 0.2 to 1 MUPa of sound pressure. This corresponds to
      thermoacoustic efficiencies ranging from 0.007 to 0.6 Pa/W for the seven devices
      that were measured in this study. Here, the small lateral dimensions of these
      devices cause large heat losses due to thermal conduction, which result in the
      relatively small observed thermoacoustic efficiencies. 

PMID- 25961804
TI  - Tuning the optical response of a dimer nanoantenna using plasmonic nanoring
      loads.
AB  - The optical properties of a dimer type nanoantenna loaded with a plasmonic
      nanoring are investigated through numerical simulations and measurements of
      fabricated prototypes. It is demonstrated that by judiciously choosing the
      nanoring geometry it is possible to engineer its electromagnetic properties and
      thus devise an effective wavelength dependent nanoswitch. The latter provides a
      mechanism for controlling the coupling between the dimer particles, and in
      particular to establish a pair of coupled/de-coupled states for the total
      structure, that effectively results in its dual mode response. Using electron
      beam lithography the targeted structure has been accurately fabricated and the
      desired dual mode response of the nanoantenna was experimentally verified. The
      response of the fabricated structure is further analyzed numerically. This
      permits the visualization of the electromagnetic fields and polarization surface
      charge distributions when the structure is at resonance. In this way the
      switching properties of the plasmonic nanoring are revealed. The documented
      analysis illustrates the inherent tuning capabilities that plasmonic nanorings
      offer, and furthermore paves the way towards a practical implementation of
      tunable optical nanoantennas. Additionally, our analysis through an effective
      medium approach introduces the nanoring as a compact and efficient solution for
      realizing nanoscale circuits. 

PMID- 25961805
TI  - Understanding the Anchoring Effect of Two-Dimensional Layered Materials for
      Lithium-Sulfur Batteries.
AB  - Although the rechargeable lithium-sulfur battery system has attracted significant
      attention due to its high theoretical specific energy, its implementation has
      been impeded by multiple challenges, especially the dissolution of intermediate
      lithium polysulfide (Li2Sn) species into the electrolyte. Introducing anchoring
      materials, which can induce strong binding interaction with Li2Sn species, has
      been demonstrated as an effective way to overcome this problem and achieve long
      term cycling stability and high-rate performance. The interaction between Li2Sn
      species and anchoring materials should be studied at the atomic level in order to
      understand the mechanism behind the anchoring effect and to identify ideal
      anchoring materials to further improve the performance of Li-S batteries. Using
      first-principles approach with van der Waals interaction included, we
      systematically investigate the adsorption of Li2Sn species on various two
      dimensional layered materials (oxides, sulfides, and chlorides) and study the
      detailed interaction and electronic structure, including binding strength,
      configuration distortion, and charge transfer. We gain insight into how van der
      Waals interaction and chemical binding contribute to the adsorption of Li2Sn
      species for anchoring materials with strong, medium, and weak interactions. We
      understand why the anchoring materials can avoid the detachment of Li2S as in
      carbon substrate, and we discover that too strong binding strength can cause
      decomposition of Li2Sn species. 

PMID- 25961806
TI  - The Pediocin PA-1 Accessory Protein Ensures Correct Disulfide Bond Formation in
      the Antimicrobial Peptide Pediocin PA-1.
AB  - Peptides, in contrast to proteins, are generally not large enough to form stable
      and well-defined three-dimensional structures. However, peptides are still able
      to form correct disulfide bonds. Using pediocin-like bacteriocins, we have
      examined how this may be achieved. Some pediocin-like bacteriocins, such as
      pediocin PA-1 and sakacin P[N24C+44C], have four cysteines. There are three
      possible ways by which the four cysteines may combine to form two disulfide
      bonds, and the three variants are expected to be produced in approximately equal
      amounts if their formation is random. Pediocin PA-1 and sakacin P[N24C+44C] with
      correct disulfide bonds were the main products when they were secreted by the
      pediocin PA-1 ABC transporter and accessory protein, but when they were secreted
      by the corresponding secretion machinery for sakacin A, a pediocin-like
      bacteriocin with one disulfide bond (two cysteines), peptides with all three
      possible disulfide bonds were produced in approximately equal amounts. All five
      cysteines in the pediocin PA-1 ABC transporter and the two cysteines (that form a
      CxxC motif) in the accessory protein were individually replaced with serines to
      examine their involvement in disulfide bond formation in pediocin PA-1. The
      Cys86Ser mutation in the accessory protein caused a 2-fold decrease in the amount
      of pediocin PA-1 with correct disulfide bonds, while the Cys83Ser mutation nearly
      abolished the production of pediocin PA-1 and resulted in the production of all
      three disufide bond variants in equal amounts. The Cys19Ser mutation in the ABC
      transporter completely abolished secretion of pediocin PA-1, suggesting that
      Cys19 is in the proteolytic active site and involved in cleaving the
      prebacteriocin. Replacing the other four cysteines in the ABC transporter with
      serines caused a slight reduction in the overall amount of secreted pediocin PA
      1, but the relative amount with the correct disulfide bonds remained large. These
      results indicate that the pediocin PA-1 accessory protein has a chaperone-like
      activity in that it ensures the formation of the correct disulfide bond in
      pediocin PA-1. 

PMID- 25961807
TI  - Proteomic Validation of Transcript Isoforms, Including Those Assembled from RNA
      Seq Data.
AB  - Human proteome analysis now requires an understanding of protein isoforms. We
      recently published the PG Nexus pipeline, which facilitates high confidence
      validation of exons and splice junctions by integrating genomics and proteomics
      data. Here we comprehensively explore how RNA-seq transcriptomics data, and
      proteomic analysis of the same sample, can identify protein isoforms. RNA-seq
      data from human mesenchymal (hMSC) stem cells were analyzed with our new
      TranscriptCoder tool to generate a database of protein isoform sequences. MS/MS
      data from matching hMSC samples were then matched against the TranscriptCoder
      derived database, along with Ensembl and the neXtProt database. Querying the
      TranscriptCoder-derived or Ensembl database could unambiguously identify ~450
      protein isoforms, with isoform-specific proteotypic peptides, including candidate
      hMSC-specific isoforms for the genes DPYSL2 and FXR1. Where isoform-specific
      peptides did not exist, groups of nonisoform-specific proteotypic peptides could
      specifically identify many isoforms. In both the above cases, isoforms will be
      detectable with targeted MS/MS assays. Unfortunately, our analysis also revealed
      that some isoforms will be difficult to identify unambiguously as they do not
      have peptides that are sufficiently distinguishing. We covisualize mRNA isoforms
      and peptides in a genome browser to illustrate the above situations. Mass
      spectrometry data is available via ProteomeXchange (PXD001449). 

PMID- 25961808
TI  - Influence of a Counterion on the Ion Atmosphere of an Anion: A Molecular Dynamics
      Study of LiX and CsX (X = F(-), Cl(-), I(-)) in Methanol.
AB  - We report molecular dynamics (MD) simulations to explore the influence of a
      counterion on the structure and dynamics of cationic and anionic solvation shells
      for various ions in methanol at 298 K. We show that the variation in ionic size
      of either the cation or the anion in an ion pair influences the solvation
      structure of the other ion as well as the diffusivity in an electrolyte solution
      of methanol. The extent of ionic association between the cation and its
      counteranion of different ionic sizes has been investigated by analyzing the
      radial distribution functions (RDFs) and the orientation of methanol molecules in
      the first solvation shell (FSS) of ions. It is shown that the methanol in the FSS
      of the anion as well the cation exhibit quite different radial and orientational
      structures as compared to methanol which lie in the FSS of either the anion or
      the cation but not both. We find that the coordination number (CN) of F(-), Cl(
      ), and I(-) ions decreases with increasing size of the anion which is contrary to
      the trend reported for the anions in H2O. The mean residence time (MRT) of
      methanol molecules in the FSS of ions has been calculated using the stable states
      picture (SSP) approach. It is seen that the ion-counterion interaction has a
      considerable influence on the MRT of methanol molecules in the FSS of ions. We
      also discuss the stability order of the ion-counterion using the potentials of
      mean force (PMFs) for ion pairs with ions of different sizes. The PMF plots
      reveal that the Li(+)-F(-) pair (small-small) is highly stable and the Li(+)-I(-)
      pair is least stable (small-large) in electrolyte solutions. 

PMID- 25961809
TI  - Correction to Rhodium-Catalyzed 1,4-Addition of Arylboronic Acids to 3
      Benzylidene-1H-pyrrolo[2,3-b]pyridin-2(3H)-one Derivatives.

PMID- 25961810
TI  - Understanding the formation mechanism of graphene frameworks synthesized by
      solvothermal and rapid pyrolytic processes based on an alcohol-sodium hydroxide
      system.
AB  - The determination of ways to facilitate the 2D-oriented assembly of carbons into
      graphene instead of other carbon structures while restraining the pi-pi stacking
      interaction is a challenge for the controllable bulk synthesis of graphene, which
      is vital both scientifically and technically. In this study, graphene frameworks
      (GFs) are synthesized by solvothermal and rapid pyrolytic processes based on an
      alcohol-sodium hydroxide system. The evolution mechanism of GFs is investigated
      systematically. Under sodium catalysis, the abundant carbon atoms produced by the
      fast decomposition of solvothermal intermediate self-assembled to graphene. The
      existence of abundant ether bonds may be favorable for 3D graphene formation.
      More importantly, GFs were successfully obtained using acetic acid as the carbon
      source in the synthetic process, suggesting the reasonability of analyzing the
      formation mechanism. It is quite possible to determine more favorable routes to
      synthesize graphene under this cognition. The electrochemical energy storage
      capacity of GFs was also studied, which revealed a high supercapacitor
      performance with a specific capacitance of 310.7 F/g at the current density of
      0.2 A/g. 

PMID- 25961812
TI  - Symptoms as the main problem in primary care: A cross-sectional study of
      frequency and characteristics.
AB  - OBJECTIVE: The aim was to study symptoms managed as the main problem by the
      general practitioner (GP) and to describe the frequencies and characteristics of
      presented symptoms when no specific diagnosis could be made. DESIGN: Cross-
      sectional study. SETTING: General practices in the Central Denmark Region.
      SUBJECTS: In total, 397 GPs included patients with face-to-face contacts during
      one randomly assigned day in 2008-2009; 7008 patients were included and 5232
      presented with a health problem. MAIN OUTCOME MEASURES: GPs answered a
      questionnaire after each patient contact. Symptoms and specific diagnoses were
      subsequently classified using the International Classification of Primary Care
      (ICPC). Symptom frequency, comorbidity, consultation length, and GP-assessed
      final outcome and burden of consultations were analysed. RESULTS: The GPs could
      not establish a specific diagnosis in 36% of patients with health problems. GPs
      expected that presented symptoms would not result in a future specific diagnosis
      for half of these patients. Musculoskeletal (lower limb and back) and respiratory
      (cough) symptoms were most frequent. More GPs had demanding consultations when no
      specific diagnosis could be made. Higher burden was associated with age,
      comorbidity, and GP expectancy of persistent symptoms when no diagnosis could be
      made. CONCLUSION: Interpretation and management of symptoms is a key task in
      primary care. As symptoms are highly frequent in general practice, symptoms
      without a specific diagnosis constitute a challenge to GPs. Nevertheless,
      symptoms have been given little priority in research. More attention should be
      directed to evidence-based management of symptoms as a generic phenomenon to
      ensure improved outcomes in the future.

PMID- 25961811
TI  - Differential diagnosis of illness in travelers arriving from Sierra Leone,
      Liberia, or Guinea: a cross-sectional study from the GeoSentinel Surveillance
      Network.
AB  - BACKGROUND: The largest-ever outbreak of Ebola virus disease (EVD), ongoing in
      West Africa since late 2013, has led to export of cases to Europe and North
      America. Clinicians encountering ill travelers arriving from countries with
      widespread Ebola virus transmission must be aware of alternate diagnoses
      associated with fever and other nonspecific symptoms. OBJECTIVE: To define the
      spectrum of illness observed in persons returning from areas of West Africa where
      EVD transmission has been widespread. DESIGN: Descriptive, using GeoSentinel
      records. SETTING: 57 travel or tropical medicine clinics in 25 countries.
      PATIENTS: 805 ill returned travelers and new immigrants from Sierra Leone,
      Liberia, or Guinea seen between September 2009 and August 2014. MEASUREMENTS:
      Frequencies of demographic and travel-related characteristics and illnesses
      reported. RESULTS: The most common specific diagnosis among 770 nonimmigrant
      travelers was malaria (n = 310 [40.3%]), with Plasmodium falciparum or severe
      malaria in 267 (86%) and non-P. falciparum malaria in 43 (14%). Acute diarrhea
      was the second most common diagnosis among nonimmigrant travelers (n = 95
      [12.3%]). Such common diagnoses as upper respiratory tract infection, urinary
      tract infection, and influenza-like illness occurred in only 26, 9, and 7
      returning travelers, respectively. Few instances of typhoid fever (n = 8), acute
      HIV infection (n = 5), and dengue (n = 2) were encountered. LIMITATION:
      Surveillance data collected by specialist clinics may not be representative of
      all ill returned travelers. CONCLUSION: Although EVD may currently drive clinical
      evaluation of ill travelers arriving from Sierra Leone, Liberia, and Guinea,
      clinicians must be aware of other more common, potentially fatal diseases.
      Malaria remains a common diagnosis among travelers seen at GeoSentinel sites.
      Prompt exclusion of malaria and other life-threatening conditions is critical to
      limiting morbidity and mortality. PRIMARY FUNDING SOURCE: Centers for Disease
      Control and Prevention.

PMID- 25961813
TI  - The temporal "pulse" of drinking: Tracking 5 years of binge drinking in emerging
      adults.
AB  - Binge drinking is associated with clinically significant individual-level and
      public health consequences. The topography of binge drinking may influence the
      emergence of consequences, but studies of topography require a higher level of
      temporal resolution than is typically available in epidemiological research. To
      address topography across the 5 "peak" years of binge drinking (18 to 23 years),
      we assessed daily binge drinking via successive 90-day timeline follow-back
      interviews of 645 young adults (resulting in almost 700,000 data points). Results
      showed a weekend "pulse" of binge drinking that remained consistent across the
      entire 5 year span, with occasional holiday-based perturbations. Two-part latent
      growth curve modeling applied to this dataset showed that the often-observed
      decrease in drinking associated with "maturing out" was due more to decreased
      participation in binge drinking occasions, rather than to amounts consumed when
      drinking (intensity). Similarly, the number of binge drinkers varied by day of
      the week, but the intensity of binge drinking, for those drinking, varied little
      by day of the week. This approach also showed distinctive predictors for
      participation and intensity; baseline expectancies and sociability accounted for
      individual differences in participation, whereas impulsivity-sensation seeking
      predicted intensity. Individual patterns of binge drinking participation and
      intensity also predicted drinking consequences over the 5 years of the study.
      Given these results, binge drinking patterns may serve as a useful phenotype for
      future research on pathological drinking.

PMID- 25961814
TI  - Tobacco withdrawal symptoms mediate motivation to reinstate smoking during
      abstinence.
AB  - Withdrawal-based theories of addiction hypothesize that motivation to reinstate
      drug use following acute abstinence is mediated by withdrawal symptoms.
      Experimental tests of this hypothesis in the tobacco literature are scant and may
      be subject to methodological limitations. This study utilized a robust within
      subject laboratory experimental design to investigate the extent to which
      composite tobacco withdrawal symptomatology level and 3 unique withdrawal
      components (i.e., low positive affect, negative affect, and urge to smoke)
      mediated the effect of smoking abstinence on motivation to reinstate smoking.
      Smokers (>=10 cigarettes per day; N = 286) attended 2 counterbalanced sessions at
      which abstinence duration was differentially manipulated (1 hr vs. 17 hr). At
      both sessions, participants reported current withdrawal symptoms and subsequently
      completed a task in which they were monetarily rewarded proportional to the
      length of time they delayed initiating smoking, with shorter latency reflecting
      stronger motivation to reinstate smoking. Abstinence reduced latency to smoking
      initiation and positive affect and increased composite withdrawal symptom level,
      urge, and negative affect. Abstinence-induced reductions in latency to initiating
      smoking were mediated by each withdrawal component, with stronger effects
      operating through urge. Combined analyses suggested that urge, negative affect,
      and low positive affect operate through empirically unique mediational pathways.
      Secondary analyses suggested similar effects on smoking quantity, few differences
      among specific urge and affect subtypes, and that dependence amplifies some
      abstinence effects. This study provides the first experimental evidence that
      within-person variation in abstinence impacts motivation to reinstate drug use
      through withdrawal. Urge, negative affect, and low positive affect may reflect
      unique withdrawal-mediated mechanisms underlying tobacco addiction.

PMID- 25961816
TI  - Commentary on "The modal suicide decedent did not consume alcohol just prior to
      the time of death: An analysis with implications for understanding suicidal
      behavior".
AB  - This is a commentary on a meta-analysis in this journal by Anestis, Joiner,
      Hanson, and Gutierrez (2014) that analyzed 92 studies reporting data on the
      presence/absence of alcohol in suicide decedents based on positive blood alcohol
      concentrations (BACs). The authors conclude that the weighted mean percentage of
      suicide decedents with positive BACs is 26.9%, a result that is underestimated by
      6.7% due to a coding error. The authors argue that acute use of alcohol may not
      be an important proximal risk factor for suicide based largely on the fact that
      it is not modal in decedents, a point that overlooks the fact that risk factors
      need not be modal to be of major public health significance. For example, most
      traffic fatalities do not involve a driver who had been drinking but this does
      not imply that alcohol use is unimportant in road deaths. Furthermore, the
      authors do not discuss controlled studies providing evidence that acute use of
      alcohol confers marked risk. The authors also predict that the percentage of
      suicide decedents with positive BACs who are intoxicated is low. However,
      published data on alcohol levels and suicide in the United States are available
      and show that most suicide decedents with positive blood tests have BACs at or
      above the U.S. legal limit of 0.08 g/dl for drinking and driving, with mean BACs
      well in excess of the legal limit, evidence of intoxication.

PMID- 25961815
TI  - Poor self-control and harsh punishment in childhood prospectively predict
      borderline personality symptoms in adolescent girls.
AB  - Developmental theories of borderline personality disorder (BPD) propose that
      harsh, invalidating parenting of a child with poor self-control and heightened
      negative emotionality often leads to a coercive cycle of parent-child
      transactions that increase risk for BPD symptoms such as emotion dysregulation.
      Although parenting practices and child temperament have previously been linked
      with BPD, less is known about the prospective influences of caregiver and child
      characteristics. Using annual longitudinal data from the Pittsburgh Girls Study
      (n = 2,450), our study examined how reciprocal influences among harsh parenting,
      self-control, and negative emotionality between ages 5 and 14 predicted the
      development of BPD symptoms in adolescent girls ages 14 to 17. Consistent with
      developmental theories, we found that harsh punishment, poor self-control, and
      negative emotionality predicted BPD symptom severity at age 14. Only worsening
      self-control between ages 12 and 14, however, predicted growth in BPD symptoms
      from 14 to 17. Furthermore, the effects of harsh punishment and poor self-control
      on age 14 BPD symptoms were partially mediated by their earlier reciprocal
      effects on each other between ages 5 and 14. Our findings underscore the need to
      address both child and parental contributions to dysfunctional transactions in
      order to stem the development of BPD symptoms. Moreover, problems with self
      regulation in early adolescence may indicate heightened risk for subsequent BPD.
      Altogether, these results increase our understanding of developmental
      trajectories associated with BPD symptoms in adolescent girls.

PMID- 25961817
TI  - Response to commentary on "The modal suicide decedent did not consume alcohol
      just prior to the time of death: An analysis with implications for understanding
      suicidal behavior".
AB  - A commentary on our article, "The Modal Suicide Decedent Did Not Consume Alcohol
      Just Prior to the Time of Death: An Analysis with Implications for Understanding
      Suicidal Behavior," published in this issue, was reviewed. We agree with the
      authors of that commentary regarding a coding error that has now been corrected.
      While we disagree with several of the points raised by the authors, the majority
      of our disagreements lie in how the results of our original study are being
      interpreted. We provide a point-by-point response to that commentary and thank
      the authors for advancing scientific debate on what we view as a very important
      issue in understanding the role of alcohol as a risk factor for suicide.

PMID- 25961818
TI  - Correction to Lowe et al. (2014).
AB  - Reports an error in "Bidirectional relationships between trauma exposure and
      posttraumatic stress: A longitudinal study of Detroit residents" by Sarah R.
      Lowe, Kate Walsh, Monica Uddin, Sandro Galea and Karestan C. Koenen (Journal of
      Abnormal Psychology, 2014[Aug], Vol 123[3], 533-544). The prevalences in Table 1
      did not correspond to the correct traumatic events due to a misalignment in rows
      and columns. All other results in the manuscript remain unchanged. The corrected
      table is provided.

PMID- 25961821
TI  - Exercise in isolation--a countermeasure for electrocortical, mental and cognitive
      impairments.
AB  - INTRODUCTION: Mental impairments, including deterioration of mood and cognitive
      performance, are known to occur during isolation and space missions, but have
      been insufficiently investigated. Appropriate countermeasures are required, such
      as exercise, which is known to prevent mood disorders for prolonged space and
      isolation missions. Based on the interaction of brain activity, mood and
      cognitive performance, this study aims to investigate the effect of long-term
      isolation and confinement and the long-term effect of exercise on these
      parameters. METHODS: Eight male volunteers were isolated and confined for about
      eight month during the winter period at the Antarctic Concordia Station. Every
      six weeks electroencephalographic measurements were recorded under rest
      conditions, and cognitive tests and a mood questionnaire were executed. Based
      individual training logs, subjects were afterwards separated into an active (>
      2500 arbitrary training units/interval) or inactive (< 2500 arbitrary training
      units/interval) group. RESULTS: A long-term effect of exercise was observed for
      brain activity and mood. Regularly active people showed a decreased brain
      activity (alpha and beta) in the course of isolation, and steady mood. Inactive
      people instead first increased and than remained at high brain activity
      accompanied with a deterioration of mood. No effect of exercise and isolation was
      found for cognitive performance. CONCLUSION: The findings point out the positive
      effect of regularly performed voluntary exercise, supporting subjective mental
      well-being of long-term isolated people. The choice to be regularly active seems
      to support mental health, which is not only of interest for future isolation and
      space missions.

PMID- 25961822
TI  - Mechanistic Basis Of Peptide-Protein Interaction In AtPep1-PEPR1 Complex In
      Arabidopsis thaliana.
AB  - Peptide-mediated immunity against pathogens in plants can provide information on
      protein-peptide interactions and drug discovery in general. The molecular
      structure of AtPep1, a 23-amino acid signaling peptide isolated from Arabidopsis
      thaliana leaves and implicated in innate immunity, has evaded structural
      determination by biophysical methods. The details of molecular interaction of
      AtPep1 peptide with its receptor (PEPR1), a 170 kDa leucine-rich repeat (LRR)
      kinase is also unknown. We report a computational approach to the modeling AtPep1
      by conformational sampling and its interaction with the receptor PEPR1. Molecular
      dynamics simulations were employed to sample and cluster energetically favorable
      conformations of AtPep1 and modeling of PEPR1 through homology. Docking of AtPep1
      to PEPR1 and filtering of the biologically relevant poses were facilitated by the
      computational Ala-scanning mutations and binding energy analysis of the peptide
      protein complex. This study provides the first independent in silico validation
      of the Structure-Activity- Relationship studies carried out on the AtPep1 and
      provides a molecular mechanism of the peptide-protein complex system. 

PMID- 25961820
TI  - Loss of Bace1 in mice does not alter the severity of caerulein induced
      pancreatitis.
AB  - CONTEXT: Beta-site alpha-amyloid protein cleaving enzyme1 (BACE1) plays a key
      role in the pathogenesis of Alzheimer's disease. Additional to its moderate
      expression in the brain, high levels of BACE1 mRNA were found in the pancreas.
      Murine Bace1 has been immunohistochemicaly detected at the apical pole of acinar
      cells within the exocrine pancreas of mice and Bace1 activity was observed in
      pancreatic juice. In vitro experiments revealed enteropeptidase as a putative
      substrate for Bace1 suggesting a role in acute pancreatitis. OBJECTIVE: The aim
      of this study was to address a protective mechanism of Bace1 in acute
      experimental pancreatitis in mice. METHODS: Acute experimental pancreatitis was
      induced by intraperitoneal injection of caerulein in homozygote Bace1-/- mice and
      wild type mice. Serum and tissue analyses were carried out after 4 h, 8 h and 24
      h. Measurement of plasma amylase and lipase was performed to confirm pancreatitis
      induction. In order to assess the severity of pancreatitis H&E stained pancreatic
      sections were examined regarding edema, inflammation and apoptosis.
      Immunohistochemical detection of myeloperoxidase (MPO) positive cells was carried
      out to further quantify the extent of inflammation. Expression of Bace2 within
      the pancreas was analyzed by immunohistochemistry and RT-qPCR. RESULTS: We
      demonstrate that total loss of Bace1 in mice leads to no alterations in the
      course of acute experimental caerulein-pancreatitis. Bace1-/- mice develop a
      moderate pancreatitis that is comparable in histomorphological and serological
      features with those seen in wild type mice. DISCUSSION: We discuss the results in
      the context of the applied caerulein induced edematous pancreatitis model and
      possible compensatory mechanisms via Bace2 that might be responsible for the
      observed results.

PMID- 25961819
TI  - Tumor Suppressor Function of the SEMA3B Gene in Human Lung and Renal Cancers.
AB  - The SEMA3B gene is located in the 3p21.3 LUCA region, which is frequently
      affected in different types of cancer. The objective of our study was to expand
      our knowledge of the SEMA3B gene as a tumor suppressor and the mechanisms of its
      inactivation. In this study, several experimental approaches were used: tumor
      growth analyses and apoptosis assays in vitro and in SCID mice, expression and
      methylation assays and other. With the use of the small cell lung cancer cell
      line U2020 we confirmed the function of SEMA3B as a tumor suppressor, and showed
      that the suppression can be realized through the induction of apoptosis and,
      possibly, associated with the inhibition of angiogenesis. In addition, for the
      first time, high methylation frequencies have been observed in both intronic (32
      39%) and promoter (44-52%) CpG-islands in 38 non-small cell lung carcinomas,
      including 16 squamous cell carcinomas (SCC) and 22 adenocarcinomas (ADC), and in
      83 clear cell renal cell carcinomas (ccRCC). Correlations between the methylation
      frequencies of the promoter and the intronic CpG-islands of SEMA3B with tumor
      stage and grade have been revealed for SCC, ADC and ccRCC. The association
      between the decrease of the SEMA3B mRNA level and hypermethylation of the
      promoter and the intronic CpG-islands has been estimated in renal primary tumors
      (P < 0.01). Using qPCR, we observed on the average 10- and 14-fold decrease of
      the SEMA3B mRNA level in SCC and ADC, respectively, and a 4-fold decrease in
      ccRCC. The frequency of this effect was high in both lung (92-95%) and renal
      (84%) tumor samples. Moreover, we showed a clear difference (P < 0.05) of the
      SEMA3B relative mRNA levels in ADC with and without lymph node metastases. We
      conclude that aberrant expression and methylation of SEMA3B could be suggested as
      markers of lung and renal cancer progression. 

PMID- 25961823
TI  - Correction: Experimental Tests of Priority Effects and Light Availability on
      Relative Performance of Myriophyllum picatum and Elodea nuttallii Propagules in
      Artificial Stream Channels.

PMID- 25961824
TI  - Comparison of glucose lowering effect of metformin and acarbose in type 2
      diabetes mellitus: a meta-analysis.
AB  - BACKGROUND: Metformin is the first-line oral hypoglycemic agent for type 2
      diabetes mellitus recommended by international guidelines. However, little
      information exists comparing it with acarbose which is also commonly used in
      China. This study expanded knowledge by combining direct and indirect evidence to
      ascertain the glucose lowering effects of both drugs. METHODS: PubMed (1980-
      December 2013) and China National Knowledge Infrastructure databases (1994
      January 2014) were systematically searched for eligible randomized controlled
      trials from Chinese and English literatures. Meta-analysis was conducted to
      estimate the glucose lowering effects of metformin vs. acarbose, or either of
      them vs. common comparators (placebo or sulphonylureas), using random- and fixed
      effect models. Bucher method with indirect treatment comparison calculator was
      applied to convert the summary estimates from the meta-analyses into weighted
      mean-difference (WMD) and 95% confidence intervals (CIs) to represent the
      comparative efficacy between metformin and acarbose. RESULTS: A total of 75
      studies were included in the analysis. In direct comparison (8 trials), metformin
      reduced glycosylated hemoglobin (HbA1c) by 0.06% more than acarbose, with no
      significant difference (WMD,-0.06%; 95% CI, -0.32% to 0.20%). In indirect
      comparisons (67 trials), by using placebo and sulphonylureas as common
      comparators, metformin achieved significant HbA1c reduction than acarbose, by 
      0.38% (WMD,-0.38%, 95% CI, -0.736% to -0.024%) and -0.34% (WMD, -0.34%, 95% CI, 
      0.651% to -0.029%) respectively. CONCLUSION: The glucose lowering effects of
      metformin monotherapy and acarbose monotherapy are the same by direct comparison,
      while metformin is a little better by indirect comparison. This implies that the
      effect of metformin is at least as good as acarbose's.

PMID- 25961825
TI  - A mass spectrometry-based assay for improved quantitative measurements of efflux
      pump inhibition.
AB  - Bacterial efflux pumps are active transport proteins responsible for resistance
      to selected biocides and antibiotics. It has been shown that production of efflux
      pumps is up-regulated in a number of highly pathogenic bacteria, including
      methicillin resistant Staphylococcus aureus. Thus, the identification of new
      bacterial efflux pump inhibitors is a topic of great interest. Existing assays to
      evaluate efflux pump inhibitory activity rely on fluorescence by an efflux pump
      substrate. When employing these assays to evaluate efflux pump inhibitory
      activity of plant extracts and some purified compounds, we observed severe
      optical interference that gave rise to false negative results. To circumvent this
      problem, a new mass spectrometry-based method was developed for the quantitative
      measurement of bacterial efflux pump inhibition. The assay was employed to
      evaluate efflux pump inhibitory activity of a crude extract of the botanical
      Hydrastis Canadensis, and to compare the efflux pump inhibitory activity of
      several pure flavonoids. The flavonoid quercetin, which appeared to be completely
      inactive with a fluorescence-based method, showed an IC50 value of 75 MUg/mL with
      the new method. The other flavonoids evaluated (apigenin, kaempferol, rhamnetin,
      luteolin, myricetin), were also active, with IC50 values ranging from 19 MUg/mL
      to 75 MUg/mL. The assay described herein could be useful in future screening
      efforts to identify efflux pump inhibitors, particularly in situations where
      optical interference precludes the application of methods that rely on
      fluorescence. 

PMID- 25961826
TI  - Channel properties of Nax expressed in neurons.
AB  - Nax is a sodium-concentration ([Na+])-sensitive Na channel with a gating
      threshold of ~150 mM for extracellular [Na+] ([Na+]o) in vitro. We previously
      reported that Nax was preferentially expressed in the glial cells of sensory
      circumventricular organs including the subfornical organ, and was involved in
      [Na+] sensing for the control of salt-intake behavior. Although Nax was also
      suggested to be expressed in the neurons of some brain regions including the
      amygdala and cerebral cortex, the channel properties of Nax have not yet been
      adequately characterized in neurons. We herein verified that Nax was expressed in
      neurons in the lateral amygdala of mice using an antibody that was newly
      generated against mouse Nax. To investigate the channel properties of Nax
      expressed in neurons, we established an inducible cell line of Nax using the
      mouse neuroblastoma cell line, Neuro-2a, which is endogenously devoid of the
      expression of Nax. Functional analyses of this cell line revealed that the [Na+]
      sensitivity of Nax in neuronal cells was similar to that expressed in glial
      cells. The cation selectivity sequence of the Nax channel in cations was revealed
      to be Na+ ~ Li+ > Rb+ > Cs+ for the first time. Furthermore, we demonstrated that
      Nax bound to postsynaptic density protein 95 (PSD95) through its PSD95/Disc
      large/ZO-1 (PDZ)-binding motif at the C-terminus in neurons. The interaction
      between Nax and PSD95 may be involved in promoting the surface expression of Nax
      channels because the depletion of endogenous PSD95 resulted in a decrease in Nax
      at the plasma membrane. These results indicated, for the first time, that Nax
      functions as a [Na+]-sensitive Na channel in neurons as well as in glial cells. 

PMID- 25961827
TI  - AKT inhibition overcomes rapamycin resistance by enhancing the repressive
      function of PRAS40 on mTORC1/4E-BP1 axis.
AB  - The mTORC1 inhibitors, rapamycin and its analogs, are known to show only modest
      antitumor activity in clinic, but the underlying mechanisms remain largely
      elusive. Here, we found that activated AKT signaling is associated with rapamycin
      resistance in breast and colon cancers by sustained phosphorylation of the
      translational repressor 4E-BP1. Treatment of tumor cells with rapamycin or the
      AKT inhibitor MK2206 showed a limited activity in inhibiting 4E-BP1
      phosphorylation, cap-dependent translation, cell growth and motility. However,
      treatment with both drugs resulted in profound effects in vitro and in vivo.
      Mechanistic investigation demonstrated that the combination treatment was
      required to effectively inhibit PRAS40 phosphorylation on both Ser183 and Thr246
      mediated by mTORC1 and AKT respectively, and with the combined treatment,
      dephosphorylated PRAS40 binding to the raptor/mTOR complex was enhanced, leading
      to dramatic repression of mTORC1-regulated 4E-BP1 phosphorylation and
      translation. Knockdown of PRAS40 or 4E-BP1 expression markedly reduced the
      dependence of tumor cells on AKT/mTORC1 signaling for translation and survival.
      Together, these findings reveal a critical role of PRAS40 as an integrator of
      mTORC1 and AKT signaling for 4E-BP1-mediated translational regulation of tumor
      cell growth and motility, and highlight PRAS40 phosphorylation as a potential
      biomarker to evaluate the therapeutic response to mTOR/AKT inhibitors. 

PMID- 25961828
TI  - Drug Dosing and Pharmacokinetics in Children With Obesity: A Systematic Review.
AB  - IMPORTANCE: Obesity affects nearly one-sixth of US children and results in
      alterations to body composition and physiology that can affect drug disposition,
      possibly leading to therapeutic failure or toxic side effects. The depth of
      available literature regarding obesity's effect on drug safety, pharmacokinetics,
      and dosing in obese children is unknown. OBJECTIVE: To perform a systematic
      literature review describing the current evidence of the effect of obesity on
      drug disposition in children. EVIDENCE REVIEW: We searched the MEDLINE, Cochrane,
      and EMBASE databases (January 1, 1970-December 31, 2012) and included studies if
      they contained data on drug clearance, volume of distribution, or drug
      concentration in obese children (aged <=18 years). We compared exposure and
      weight-normalized volume of distribution and clearance between obese and nonobese
      children. We explored the association between drug physicochemical properties and
      clearance and volume of distribution. FINDINGS: Twenty studies met the inclusion
      criteria and contained pharmacokinetic data for 21 drugs. The median number of
      obese children studied per drug was 10 (range, 1-112) and ages ranged from
      newborn to 29 years (1 study described pharmacokinetics in children and adults
      together). Dosing schema varied and were either a fixed dose (6 [29%]) or based
      on body weight (10 [48%]) and body surface area (4 [19%]). Clinically significant
      pharmacokinetic alterations were observed in obese children for 65% (11 of 17) of
      the studied drugs. Pharmacokinetic alterations resulted in substantial
      differences in exposure between obese and nonobese children for 38% (5 of 13) of
      the drugs. We found no association between drug lipophilicity or
      Biopharmaceutical Drug Disposition Classification System class and changes in
      volume of distribution or clearance due to obesity. CONCLUSIONS AND RELEVANCE:
      Consensus is lacking on the most appropriate weight-based dosing strategy for
      obese children. Prospective pharmacokinetic trials in obese children are needed
      to ensure therapeutic efficacy and enhance drug safety.

PMID- 25961829
TI  - Use of Nondisclosure Agreements in Medical Malpractice Settlements by a Large
      Academic Health Care System.
AB  - IMPORTANCE: Honesty and transparency are essential aspects of health care,
      including in physicians' and hospitals' responses to medical error. Biases and
      habits associated with medical malpractice litigation, however, may work at cross
      purposes with compassion in clinical care and with efforts to improve patient
      safety. OBJECTIVE: To determine the frequency of nondisclosure agreements in
      medical malpractice settlements and the extent to which the restrictions in these
      agreements seem incompatible with good patient care. DESIGN, SETTING, AND
      PARTICIPANTS: We performed a retrospective review of medical malpractice claim
      files, including settlement agreements, for claims closed before (fiscal year
      2001-2002), during (fiscal year 2006-2007), and after (fiscal years 2009-2012)
      the implementation of tort reform in Texas. We studied The University of Texas
      System, which self-insures malpractice claims that involve 6000 physicians at 6
      medical campuses in 5 cities. MAIN OUTCOMES AND MEASURES: Nondisclosure
      provisions in medical malpractice settlements. RESULTS: During the 5 study years,
      The University of Texas System closed 715 malpractice claims and made 150
      settlement payments. For the 124 cases that met our selection criteria, the
      median compensation paid by the university was $100,000 (range, $500-$1.25
      million), and the mean compensation was $185,372. A total of 110 settlement
      agreements (88.7%) included nondisclosure provisions. All the nondisclosure
      clauses prohibited disclosure of the settlement terms and amount, 61 (55.5%)
      prohibited disclosure that the settlement had been reached, 51 (46.4%) prohibited
      disclosure of the facts of the claim, 29 (26.4%) prohibited reporting to
      regulatory agencies, and 10 (9.1%) prohibited disclosure by the settling
      physicians and hospitals, not only by the claimant. Three agreements (2.7%)
      included specific language that prohibited the claimant from disparaging the
      physicians or hospitals. The 50 settlement agreements signed after tort reform
      took full effect in Texas (2009-2012) had stricter nondisclosure provisions than
      the 60 signed in earlier years: settlements after tort reform were more likely to
      prohibit disclosure of the event of settlement (36 [72.0%] vs 25 [41.7%]; P <
      .001), to prohibit disclosure of the facts of the claims (31 [62.0%] vs 20
      [33.3%]; P = .003), and to prohibit reporting to regulatory bodies (25 [50.0%] vs
      4 [6.7%]; P < .001). CONCLUSIONS AND RELEVANCE: An academic health system with a
      declared commitment to patient safety and transparency used nondisclosure clauses
      in most malpractice settlement agreements but with little standardization or
      consistency. The scope of nondisclosure was often broader than seemed needed to
      protect physicians and hospitals from disparagement by the plaintiff or to avoid
      publicizing settlement amounts that might attract other claimants. Some
      agreements prohibited reporting to regulatory agencies, a practice that the
      health system changed in response to our findings.

PMID- 25961832
TI  - Summaries for Patients. Sexual Orientation Identity and Human Papillomavirus
      Vaccination.

PMID- 25961831
TI  - Regional versus General Anesthesia for Percutaneous Nephrolithotomy: A Meta
      Analysis.
AB  - OBJECTIVE: To compare the effectiveness and safety of regional anesthesia (RA)
      and general anesthesia (GA) for percutaneous nephrolithotomy (PNL). PATIENTS AND
      METHODS: PubMed, EMBASE, The Cochrane Library, and the Web of Knowledge databases
      were systematically searched to identify relevant studies. After literature
      screening and data extraction, a meta-analysis was performed using the RevMan 5.3
      software. RESULTS: Eight randomized controlled trials (RCTs) and six non
      randomized controlled trials (nRCTs) involving 2270 patients were included.
      Patients receiving RA were associated with shorter operative time (-6.22 min;
      95%CI, -9.70 to -2.75; p = 0.0005), lower visual analgesic score on the first and
      third postoperative day (WMD, -2.62; 95%CI, -3.04 to -2.19; p < 0.00001 WMD, 
      0.38; 95%CI, -0.58 to -0.18; p = 0.0002), less analgesic requirements (WMD, 
      59.40 mg; 95%CI, -78.39 to -40.40; p<0.00001), shorter hospitalization (WMD, 
      0.36d; 95%CI, -0.66 to -0.05; p = 0.02), less blood transfusion (RR, 0.61; 95%CI,
      0.41 to 0.93; p = 0.02), fewer modified Clavion-Dindo Grade II (RR, 0.56; 95%CI,
      0.37 to 0.83; p = 0.005), Grade III or above postoperative complications (RR,
      0.51; 95%CI, 0.33 to 0.77; p = 0.001), and potential benefits of less fever (RR,
      0.79; 95%CI, 0.61 to 1.02; p = 0.07), nausea or vomiting (RR, 0.54; 95%CI, 0.20
      to 1.46; p = 0.23), whereas more intraoperative hypotension (RR, 3.13; 95%CI,
      1.76 to 5.59; p = 0.0001) when compared with patients receiving GA. When nRCTs
      were excluded, most of the results were stable but the significant differences
      were no longer detectable in blood transfusion, Grade II and more severe
      complications. No significant difference in the total postoperative complications
      and stone-free rate were found. CONCLUSIONS: Current evidence suggests that both
      RA and GA can provide safe and effective anesthesia for PNL in carefully
      evaluated and selected patients. Each anesthesia technique has its own advantages
      but some aspects still remain unclear and need to be explored in future studies.

PMID- 25961830
TI  - Altered KLOTHO and NF-kappaB-TNF-alpha Signaling Are Correlated with Nephrectomy
      Induced Cognitive Impairment in Rats.
AB  - Renal insufficiency can have a negative impact on cognitive function.
      Neuroinflammation and changes in klotho levels associate with chronic kidney
      disease (CKD) and may play a role in the development of cognitive impairment
      (CI). The present study evaluates the correlation of cognitive deficits with
      neuroinflammation and soluble KLOTHO in the cerebral spinal fluid (CSF) and brain
      tissue of nephrectomized rats (Nx), with 5/6 renal mass ablation. Nx and sham
      Munich Wistar rats were tested over 4 months for locomotor activity, as well as
      inhibitory avoidance or novel object recognition, which started 30 days after the
      surgery. EMSA for Nuclear factor-kappaB and MILLIPLEXMAP or ELISA kit were used
      to evaluate cytokines, glucocorticoid and KLOTHO levels. Nx animals that showed a
      loss in aversive-related memory and attention were included in the CI group (Nx
      CI) (n=14) and compared to animals with intact learning (Nx-M n=12 and Sham n=20
      groups). CSF and tissue samples were collected 24 hours after the last behavioral
      test. The results show that the Nx-groups have increased NF-kappaB binding
      activity and tumor necrosis factor-alpha (TNF-alpha) levels in the hippocampus
      and frontal cortex, with these changes more pronounced in the Nx-CI group frontal
      cortex. In addition, the Nx-CI group showed significantly increased CSF
      glucocorticoid levels and TNF-alpha /IL-10 ratio compared to the Sham group.
      Klotho levels were decreased in Nx-CI frontal cortex but not in hippocampus, when
      compared to Nx-M and Sham groups. Overall, these results suggest that
      neuroinflammation mediated by frontal cortex NF-kappaB, TNF-alpha and KLOTHO
      signaling may contribute to Nx-induced CI in rats. 

PMID- 25961833
TI  - Anticancer Effect of Ginger Extract against Pancreatic Cancer Cells Mainly
      through Reactive Oxygen Species-Mediated Autotic Cell Death.
AB  - The extract of ginger (Zingiber officinale Roscoe) and its major pungent
      components, [6]-shogaol and [6]-gingerol, have been shown to have an anti
      proliferative effect on several tumor cell lines. However, the anticancer
      activity of the ginger extract in pancreatic cancer is poorly understood. Here,
      we demonstrate that the ethanol-extracted materials of ginger suppressed cell
      cycle progression and consequently induced the death of human pancreatic cancer
      cell lines, including Panc-1 cells. The underlying mechanism entailed autosis, a
      recently characterized form of cell death, but not apoptosis or necroptosis. The
      extract markedly increased the LC3-II/LC3-I ratio, decreased SQSTM1/p62 protein,
      and enhanced vacuolization of the cytoplasm in Panc-1 cells. It activated AMPK, a
      positive regulator of autophagy, and inhibited mTOR, a negative autophagic
      regulator. The autophagy inhibitors 3-methyladenine and chloroquine partially
      prevented cell death. Morphologically, however, focal membrane rupture, nuclear
      shrinkage, focal swelling of the perinuclear space and electron dense
      mitochondria, which are unique morphological features of autosis, were observed.
      The extract enhanced reactive oxygen species (ROS) generation, and the
      antioxidant N-acetylcystein attenuated cell death. Our study revealed that daily
      intraperitoneal administration of the extract significantly prolonged survival (P
      = 0.0069) in a peritoneal dissemination model and suppressed tumor growth in an
      orthotopic model of pancreatic cancer (P < 0.01) without serious adverse effects.
      Although [6]-shogaol but not [6]-gingerol showed similar effects, chromatographic
      analyses suggested the presence of other constituent(s) as active substances.
      Together, these results show that ginger extract has potent anticancer activity
      against pancreatic cancer cells by inducing ROS-mediated autosis and warrants
      further investigation in order to develop an efficacious candidate drug. 

PMID- 25961834
TI  - The Repellent DEET Potentiates Carbamate Effects via Insect Muscarinic Receptor
      Interactions: An Alternative Strategy to Control Insect Vector-Borne Diseases.
AB  - Insect vector-borne diseases remain one of the principal causes of human
      mortality. In addition to conventional measures of insect control, repellents
      continue to be the mainstay for personal protection. Because of the increasing
      pyrethroid-resistant mosquito populations, alternative strategies to reconstitute
      pyrethroid repellency and knock-down effects have been proposed by mixing the
      repellent DEET (N,N-Diethyl-3-methylbenzamide) with non-pyrethroid insecticide to
      better control resistant insect vector-borne diseases. By using
      electrophysiological, biochemichal, in vivo toxicological techniques together
      with calcium imaging, binding studies and in silico docking, we have shown that
      DEET, at low concentrations, interacts with high affinity with insect M1/M3 mAChR
      allosteric site potentiating agonist effects on mAChRs coupled to phospholipase C
      second messenger pathway. This increases the anticholinesterase activity of the
      carbamate propoxur through calcium-dependent regulation of acetylcholinesterase.
      At high concentrations, DEET interacts with low affinity on distinct M1/M3 mAChR
      site, counteracting the potentiation. Similar dose-dependent dual effects of DEET
      have also been observed at synaptic mAChR level. Additionally, binding and in
      silico docking studies performed on human M1 and M3 mAChR subtypes indicate that
      DEET only displays a low affinity antagonist profile on these M1/M3 mAChRs. These
      results reveal a selective high affinity positive allosteric site for DEET in
      insect mAChRs. Finally, bioassays conducted on Aedes aegypti confirm the
      synergistic interaction between DEET and propoxur observed in vitro, resulting in
      a higher mortality of mosquitoes. Our findings reveal an unusual allosterically
      potentiating action of the repellent DEET, which involves a selective site in
      insect. These results open exciting research areas in public health particularly
      in the control of the pyrethroid-resistant insect-vector borne diseases. Mixing
      low doses of DEET and a non-pyrethroid insecticide will lead to improvement in
      the efficiency treatments thus reducing both the concentration of active
      ingredients and side effects for non-target organisms. The discovery of this
      insect specific site may pave the way for the development of new strategies
      essential in the management of chemical use against resistant mosquitoes. 

PMID- 25961835
TI  - Macular grid laser photocoagulation for branch retinal vein occlusion.
AB  - BACKGROUND: Branch retinal vein occlusion (BRVO) is the second most common cause
      of retinal vascular abnormality after diabetic retinopathy. Persistent macular
      oedema develops in 60% of eyes with a BRVO. Untreated, only 14% of eyes with
      chronic macular oedema will have a visual acuity (VA) of 20/40 or better. Macular
      grid laser photocoagulation is used for chronic non-ischaemic macular oedema
      following BRVO and has been the mainstay of treatment for over 20 years. New
      treatments are available and a systematic review is necessary to ensure that the
      most up-to-date evidence is considered objectively. OBJECTIVES: To examine the
      effects of macular grid laser photocoagulation in the treatment of macular oedema
      following BRVO. SEARCH METHODS: We searched CENTRAL, Ovid MEDLINE, EMBASE, Web of
      Science Conference Proceedings Citation Index, the metaRegister of Controlled
      Trials (mRCT), ClinicalTrials.gov and the WHO International Clinical Trials
      Registry Platform. We did not use any date or language restrictions in the
      electronic searches for trials. We last searched the electronic databases on 21
      August 2014. SELECTION CRITERIA: We included randomised controlled trials (RCTs)
      comparing macular grid laser photocoagulation treatment to another treatment,
      sham treatment or no treatment. DATA COLLECTION AND ANALYSIS: We used standard
      methodological procedures expected by Cochrane. MAIN RESULTS: We included five
      studies conducted in Europe and North America. Four separate trials compared grid
      laser to no treatment, sham treatment, intravitreal bevacizumab and intravitreal
      triamcinolone. One further trial compared subthreshold to threshold laser. Two of
      these trials were judged to be at high risk of bias in one or more domains.In one
      trial of grid laser versus observation, people receiving grid laser were more
      likely to gain visual acuity (VA) (10 or more ETDRS letters) at 36 months (RR
      1.75, 95% confidence interval (CI) 1.08 to 2.84, 78 participants, moderate
      quality evidence). The effect of grid laser on loss of VA (10 or more letters)
      was uncertain as the results were imprecise (RR 0.68, 95% CI 0.23 to 2.04, 78
      participants, moderate-quality evidence). On average, people receiving grid laser
      had better improvement in VA (mean difference (MD) 0.11 logMAR, 95% CI 0.05 to
      0.17, high-quality evidence). In a trial of early and delayed grid laser
      treatment versus sham laser (n = 108, data available for 99 participants), no
      participant gained or lost VA (15 or more ETDRS letters). At 12 months, there was
      no evidence for a difference in change in VA (from baseline) between early grid
      laser and sham laser (MD -0.03 logMAR, 95% confidence interval (CI) -0.07 to
      0.01, 68 participants, low-quality evidence) or between delayed grid laser and
      sham laser (MD 0.00, 95% CI -0.04 to 0.04, 66 participants, low-quality
      evidence).The relative effects of subthreshold and threshold laser were
      uncertain. In one trial, the RR for gain of VA (15 or more letters) at 12 months
      was 1.68 (95% CI 0.57 to 4.95, 36 participants, moderate-quality evidence); the
      RR for loss of VA (15 or more letters) was 0.56 (95% CI 0.06 to 5.63, moderate
      quality evidence); and at 24 months the change in VA from baseline was MD 0.07
      (95% CI -0.10 to 0.24, moderate-quality evidence).The relative effects of macular
      grid laser and intravitreal bevacizumab were uncertain. In one trial, the RR for
      gain of 15 or more letters at 12 months was 0.67 (95% CI 0.39 to 1.14, 30
      participants, low-quality evidence). Loss of 15 or more letters was not reported.
      Change in VA at 12 months was MD 0.11 logMAR (95% CI -0.36 to 0.14, low-quality
      evidence).The relative effects of grid laser and 1mg triamcinolone were uncertain
      at 12 months. RR for gain of VA (15 or more letters) was 1.13 (95% CI 0.75 to
      1.71, 1 RCT, 242 participants, moderate-quality evidence); RR for loss of VA (15
      or more letters) was 1.20 (95% CI 0.63 to 2.27, moderate-quality evidence); MD
      for change in VA was -0.03 letters (95% CI -0.12 to 0.06, moderate-quality
      evidence). Similar results were seen for the comparison with 4mg triamcinolone.
      Beyond 12 months, the visual outcomes were in favour of grid laser at 24 months
      and 36 months with people in the macular grid group gaining more VA.Four studies
      reported on adverse effects. Laser photocoagulation appeared to be well tolerated
      in the studies. One participant (out of 71) suffered a perforation of Bruch's
      membrane, but this did not affect visual acuity. AUTHORS' CONCLUSIONS: Moderate
      quality evidence from one RCT supports the use of grid laser photocoagulation to
      treat macular oedema following BRVO. There was insufficient evidence to support
      the use of early grid laser or subthreshold laser. There was insufficient
      evidence to show a benefit of intravitreal triamcinolone or anti-vascular
      endothelial growth factor (VEGF) over macular grid laser photocoagulation in
      BRVO. With recent interest in the use of intravitreal anti-VEGF or steroid
      therapy, assessment of treatment efficacy (change in visual acuity and foveal or
      central macular thickness using optical coherence tomography (OCT)) and the
      number of treatments needed for maintenance and long-term safety will be
      important for future studies.

PMID- 25961836
TI  - Progressive rise in red blood cell distribution width predicts mortality and
      cardiovascular events in end-stage renal disease patients.
AB  - Red blood cell distribution width (RDW) is a robust marker of adverse clinical
      outcomes in various populations. However, the clinical significance of a
      progressive rise in RDW is undetermined in end-stage renal disease (ESRD)
      patients. The purpose of this study was to determine the prognostic importance of
      a change in RDW in ESRD patients. Three hundred twenty-six incident dialysis
      patients were retrospectively analyzed. Temporal changes in RDW during 12 months
      after dialysis initiation were assessed by calculating the coefficients by linear
      regression. Patients were divided into two groups: an RDW-decreased group who had
      negative coefficient values (n = 177) and an RDW-increased group who had positive
      values (n = 149). The associations between rising RDW and mortality and
      cardiovascular (CV) events were investigated. During a median follow-up of 2.7
      years (range, 1.0-7.7 years), 75 deaths (24.0%) and 60 non-fatal CV events
      (18.4%) occurred. The event-free survival rate for the composite of end-points
      was lower in the RDW-increased group (P = 0.004). After categorizing patients
      according to baseline RDW, the event-free survival rate was lowest in patients
      with a baseline RDW >14.9% and increased RDW, and highest in patients with a
      baseline RDW <=14.9% and decreased RDW (P = 0.02). In multivariate analysis,
      rising RDW was independently associated with the composite of end-points (hazard
      ratio = 1.75, P = 0.007), whereas the baseline RDW was not. This study shows that
      a progressive rise in RDW independently predicted mortality and CV events in ESRD
      patients. Rising RDW could be an additive predictor for adverse CV outcomes ESRD
      patients. 

PMID- 25961837
TI  - Do alcohol advertisements for brands popular among underage drinkers have greater
      appeal among youth and young adults?
AB  - BACKGROUND: No previous study has determined whether there are differences in the
      youth appeal of alcohol advertisements for popular versus unpopular brands among
      underage drinkers. This paper provides a systematic investigation of the
      differential appeal of brand-level alcohol advertisements among underage youth
      and young adults in the United States. METHODS: We examined 3 issues of 8
      magazines popular among underage youth. From the advertised alcohol brands, we
      selected the ads for the top 10 and bottom 10 brands by prevalence of underage
      youth consumption, based on the results of a previous national survey. We
      assessed the ads' appeal using a sample of 211 students recruited from 1 graduate
      and 2 undergraduate courses at Boston University. Respondents rated the appeal of
      each advertisement on 4 dimensions: physical and social appeal, appeal to
      underage youth, perceived effectiveness, and liking. Using random-effects linear
      regression, we compared the appeal of advertisements for popular versus unpopular
      brands. RESULTS: On each dimension, the ads for popular youth alcohol brands were
      rated as significantly more appealing than the ads for unpopular brands. The
      magnitude of this difference was 0.26 standard deviation for the physical and
      social appeal score, 0.25 for the appeal to underage youth score, 0.21 for the
      perceived effectiveness score, and 0.16 for the liking score. CONCLUSIONS:
      Advertising for alcohol brands that are popular among youth contain elements that
      are more likely to appeal to underage youth and young adults than ads for brands
      that are relatively unpopular among young drinkers.

PMID- 25961838
TI  - Inhibin Biosynthesis and Activity Are Limited by a Prodomain-Derived Peptide.
AB  - Gonadal-derived inhibin A and B are essential factors in mammalian reproduction,
      negatively regulating pituitary production of FSH. Inhibins are synthesized as
      heterodimers of alpha- and beta-subunits, each comprising an N-terminal pro- and
      C-terminal mature domain. After dimerization, the inhibin alpha- and beta-subunit
      prodomains are enzymatically cleaved from the mature domains at consensus RXXR
      sites (site1). Interestingly, the inhibin alpha-subunit is a unique TGF-beta
      ligand, comprising a second cleavage site (site2) within its prodomain. Cleavage
      at site2 in the inhibin alpha-subunit prodomain releases a 43-amino acid proalpha
      peptide. We aimed to determine the influence of the proalpha-peptide on inhibin
      synthesis and bioactivity. Blocking proalpha-peptide release by silencing
      cleavage site2 (Arg56-Arg61) inhibited both inhibin A and B synthesis. Ligand
      blot analysis and solid-phase binding assays indicated that the proalpha-peptide
      binds specifically to a mature 30-kDa inhibin (mean Kd 86 nM) but was unable to
      bind related activins. The proalpha-peptide suppressed inhibin A and B
      bioactivity in primary rat pituitary cell cultures. Mechanistically, the proalpha
      peptide blocked inhibin A binding to its coreceptor, betaglycan (IC50 131 nM),
      and the subsequent sequestration of the activin type II receptor (IC50 156 nM),
      which underscores inhibin's biological activity. Based on the sequential
      mutations across the inhibin alpha-subunit, the proalpha-peptide binding site was
      localized to residues Arg341-Thr354, corresponding directly to the betaglycan
      binding region. Together our findings indicate that the proalpha-peptide limits
      the synthesis and bioactivity of inhibins. 

PMID- 25961840
TI  - Pressure Overload-Induced Cardiac Dysfunction in Aged Male Adiponectin Knockout
      Mice Is Associated With Autophagy Deficiency.
AB  - Heart failure is a leading cause of death, especially in the elderly or obese and
      diabetic populations. Various remodeling events have been characterized, which
      collectively contribute to the progression of heart failure. Of particular
      interest, autophagy has recently emerged as an important determinant of cardiac
      remodeling and function. Here, we used aged, 13-month-old, male adiponectin
      knockout (Ad-KO) or wild-type (wt) mice subjected to aortic banding to induce
      pressure overload (PO). Cardiac strain analysis using speckle tracking
      echocardiography indicated significant dysfunction at an earlier stage in Ad-KO
      than wt. Analysis of autophagy by Western blotting for Light Chain 3 or
      microtubule-associated proteins 1B and Sequestosome 1 together with transmission
      electron microscopy of left ventricular tissue indicated a lack of PO-induced
      cardiac autophagy in Ad-KO compared with wt mice. Associated with this was
      mitochondrial degeneration and evidence of enhanced endoplasmic reticulum stress.
      Western blotting for Light Chain 3 or microtubule-associated proteins 1B,
      examination of flux using tandem fluoresent tagged-Light Chain 3, and analysis of
      lysosomal activity in H9c2 cardiac myoblasts treated with adiponectin indicated
      that adiponectin enhanced autophagy flux. In conclusion, adiponectin directly
      stimulates autophagic flux and the lack of autophagy in response to PO in aged
      mice lacking adiponectin may contribute to cellular events which exacerbate the
      development of cardiac dysfunction. 

PMID- 25961839
TI  - Control of Polyamine Biosynthesis by Antizyme Inhibitor 1 Is Important for
      Transcriptional Regulation of Arginine Vasopressin in the Male Rat Hypothalamus.
AB  - The polyamines spermidine and spermine are small cations present in all living
      cells. In the brain, these cations are particularly abundant in the neurons of
      the paraventricular (PVN) and supraoptic nuclei (SON) of the hypothalamus, which
      synthesize the neuropeptide hormones arginine vasopressin (AVP) and oxytocin. We
      recently reported increased mRNA expression of antizyme inhibitor 1 (Azin1), an
      important regulator of polyamine synthesis, in rat SON and PVN as a consequence
      of 3 days of dehydration. Here we show that AZIN1 protein is highly expressed in
      both AVP- and oxytocin-positive magnocellular neurons of the SON and PVN together
      with antizyme 1 (AZ1), ornithine decarboxylase, and polyamines. Azin1 mRNA
      expression increased in the SON and PVN as a consequence of dehydration, salt
      loading, and acute hypertonic stress. In organotypic hypothalamic cultures,
      addition of the irreversible ornithine decarboxylase inhibitor DL-2
      (difluoromethyl)-ornithine hydrochloride significantly increased the abundance of
      heteronuclear AVP but not heteronuclear oxytocin. To identify the function of
      Azin1 in vivo, lentiviral vectors that either overexpress or knock down Azin1
      were stereotaxically delivered into the SON and/or PVN. Azin1 short hairpin RNA
      delivery resulted in decreased plasma osmolality and had a significant effect on
      food intake. The expression of AVP mRNA was also significantly increased in the
      SON by Azin1 short hairpin RNA. In contrast, Azin1 overexpression in the SON
      decreased AVP mRNA expression. We have therefore identified AZIN1, and hence by
      inference, polyamines as novel regulators of the expression of the AVP gene. 

PMID- 25961841
TI  - Activins A and B Regulate Fate-Determining Gene Expression in Islet Cell Lines
      and Islet Cells From Male Mice.
AB  - TGFbeta superfamily ligands, receptors, and second messengers, including activins
      A and B, have been identified in pancreatic islets and proposed to have important
      roles regulating development, proliferation, and function. We previously
      demonstrated that Fstl3 (an antagonist of activin activity) null mice have larger
      islets with beta-cell hyperplasia and improved glucose tolerance and insulin
      sensitivity in the absence of altered beta-cell proliferation. This suggested the
      hypothesis that increased activin signaling influences beta-cell expansion by
      destabilizing the alpha-cell phenotype and promoting transdifferentiation to beta
      cells. We tested the first part of this hypothesis by treating alpha- and beta
      cell lines and sorted mouse islet cells with activin and related ligands.
      Treatment of the alphaTC1-6 alpha cell line with activins A or B suppressed
      critical alpha-cell gene expression, including Arx, glucagon, and MafB while also
      enhancing beta-cell gene expression. In INS-1E beta-cells, activin A treatment
      induced a significant increase in Pax4 (a fate determining beta-cell gene) and
      insulin expression. In sorted primary islet cells, alpha-cell gene expression was
      again suppressed by activin treatment in alpha-cells, whereas Pax4 was enhanced
      in beta-cells. Activin treatment in both cell lines and primary cells resulted in
      phosphorylated mothers against decapentaplegic-2 phosphorylation. Finally,
      treatment of alphaTC1-6 cells with activins A or B significantly inhibited
      proliferation. These results support the hypothesis that activin signaling
      destabilized the alpha-cell phenotype while promoting a beta-cell fate. Moreover,
      these results support a model in which the beta-cell expansion observed in Fstl3
      null mice may be due, at least in part, to enhanced alpha- to beta-cell
      transdifferentiation. 

PMID- 25961843
TI  - Adjustment capacity of maritime pine cambial activity in drought-prone
      environments.
AB  - Intra-annual density fluctuations (IADFs) are anatomical features formed in
      response to changes in the environmental conditions within the growing season.
      These anatomical features are commonly observed in Mediterranean pines, being
      more frequent in younger and wider tree rings. However, the process behind IADF
      formation is still unknown. Weekly monitoring of cambial activity and wood
      formation would fill this void. Although studies describing cambial activity and
      wood formation have become frequent, this knowledge is still fragmentary in the
      Mediterranean region. Here we present data from the monitoring of cambial
      activity and wood formation in two diameter classes of maritime pine (Pinus
      pinaster Ait.), over two years, in order to test: (i) whether the differences in
      stem diameter in an even-aged stand were due to timings and/or rates of
      xylogenesis; (ii) if IADFs were more common in large trees; and (iii) if their
      formation is triggered by cambial resumption after the summer drought. Larger
      trees showed higher rates of cell production and longer growing seasons, due to
      an earlier start and later end of xylogenesis. When a drier winter occurs, larger
      trees were more affected, probably limiting xylogenesis in the summer months. In
      both diameter classes a latewood IADF was formed in 2012 in response to late
      September precipitation, confirming that the timing of the precipitation event
      after the summer drought is crucial in determining the resumption of cambial
      activity and whether or not an IADF is formed. It was the first time that the
      formation of a latewood IADF was monitored at a weekly time scale in maritime
      pine. The capacity of maritime pine to adjust cambial activity to the current
      environmental conditions represents a valuable strategy under the future climate
      change conditions. 

PMID- 25961842
TI  - OPG Treatment Prevents Bone Loss During Lactation But Does Not Affect Milk
      Production or Maternal Calcium Metabolism.
AB  - Lactation is associated with increased bone turnover and rapid bone loss, which
      liberates skeletal calcium used for milk production. Previous studies suggested
      that an increase in the skeletal expression of receptor activator of nuclear
      factor kappa-light-chain-enhancer of activated B cells ligand (RANKL) coupled
      with a decrease in osteoprotegerin (OPG) levels likely triggered bone loss during
      lactation. In this study, we treated lactating mice with recombinant OPG to
      determine whether bone loss during lactation was dependent on RANKL signaling and
      whether resorption of the maternal skeleton was required to support milk
      production. OPG treatment lowered bone resorption rates and completely prevented
      bone loss during lactation but, surprisingly, did not decrease osteoclast
      numbers. In contrast, OPG was quite effective at lowering osteoblast numbers and
      inhibiting bone formation in lactating mice. Furthermore, treatment with OPG
      during lactation prevented the usual anabolic response associated with reversal
      of lactational bone loss after weaning. Preventing bone loss had no appreciable
      effect on milk production, milk calcium levels, or maternal calcium homeostasis
      when mice were on a standard diet. However, when dietary calcium was restricted,
      treatment with OPG caused maternal hypocalcemia, maternal death, and decreased
      milk production. These studies demonstrate that RANKL signaling is a requirement
      for bone loss during lactation, and suggest that osteoclast activity may be
      required to increase osteoblast numbers during lactation in preparation for the
      recovery of bone mass after weaning. These data also demonstrate that maternal
      bone loss is not absolutely required to supply calcium for milk production unless
      dietary calcium intake is inadequate. 

PMID- 25961844
TI  - Cross-Sectional and Prospective Associations between Physical Activity and C
      Reactive Protein in Males.
AB  - BACKGROUND: There is conflicting evidence about the association between physical
      activity and inflammatory markers. Few prospective studies are available,
      particularly from low and middle-income countries. This study was aimed at
      assessing the cross-sectional and prospective associations between physical
      activity and C-reactive protein (CRP) levels in males belonging to the 1982
      Pelotas (Brazil) Birth Cohort Study. METHODS: The sample comprised 2,213 males
      followed up at the ages of 18 and 23 years. We performed high sensitivity CRP
      assays; we used a cut-off of 3 mg/L in categorical analyses. We measured physical
      activity by self-report at ages 18 and 23 years. Body mass index and waist
      circumference were studies as possible mediators. RESULTS: CRP levels above the
      3mg/L cut-off were found in 13.3% (95%CI: 11.7; 14.8) of the individuals. We
      found no evidence for an association between physical activity (leisure-time or
      all-domains) and either continuous (geometrical mean) or categorical CRP. We
      confirmed these null findings in (a) prospective and cross-sectional analyses;
      (b) trajectories analyses. CONCLUSIONS: There was no association between CRP
      levels and physical activity levels in early adulthood in a large birth cohort.
      Little variability in CRP at this early age is the likely explanation for these
      null findings.

PMID- 25961846
TI  - Impact of Conditional miRNA126 Overexpression on Apoptosis-Resistant Endothelial
      Cell Production.
AB  - The activation of endothelial cells is essential to repair damage caused by
      atherosclerosis via endothelial cell proliferation and migration. Overexpression
      of VEGF (vascular endothelial growth factor) and the downstream gene, B-cell
      lymphoma-2 (BCL-2) could result in apoptosis-resistant endothelial cells, which
      are responsible for aggravated hyperplasia and instable plaques generation.
      Previous studies have shown that miRNA126 could regulate the expression of VEGF.
      Here, we verified the existence of a miRNA126 binding site in VEGF's 3'UTR.
      Additionally, VEGF regulated BCL-2 expression via AP1 (Activator Protein 1)
      binding site in BCL-2's promoter. Next, we established an apoptosis-resistant
      endothelial cell line and constructed a lentiviral vector to express miRNA126
      under the control of the BCL-2 promoter to investigate whether conditional
      expression of miRNA126 could modulate VEGF and BCL-2 expression in apoptosis
      resistant endothelial cells. This lentiviral system specifically expressed
      miRNA126 in cells with high BCL-2 levels, downregulated VEGF expression,
      inhibited MAPK pathway activation and downregulated BCL-2 expression via
      suppression of AP1, and as a whole, reduced apoptosis-resistant endothelial
      cells, while the effects of miRNA126 on normal endothelial cells were relatively
      small. Our results demonstrate that conditional miRNA126 overexpression under the
      control of the downstream BCL-2 promoter provides a flexible regulatory strategy
      for reducing the apoptosis-resistant endothelial cells without having a
      significant impact on normal endothelial cells. 

PMID- 25961847
TI  - Clinical Features, Psychiatric Assessment, and Longitudinal Outcome of Suicide
      Attempters Admitted to a Tertiary Emergency Hospital.
AB  - The objective of this study was to characterize admissions to an emergency
      hospital due to suicide attempts and verify outcomes in 2 years. Data were
      collected from medical records and were analyzed using descriptive statistics and
      logistic regression. The sample consisted of 412 patients (58.7% women; mean age
      = 32.6 years old, SD = 14.3). Self-poisoning was the most frequent method
      (84.0%), and they were diagnosed mainly as depressive (40.3%) and borderline
      personality disorders (19.1%). Previous suicide attempts and current psychiatric
      treatment were reported by, respectively, 32.0% and 28.4%. Fifteen patients
      (3.6%, 9 males) died during hospitalization. At discharge, 79.3% were referred to
      community-based psychiatric services. Being male (OR = 2.11; 95% CI = 1.25-3.55),
      using violent methods (i.e., hanging, firearms, and knives) (OR = 1.96; 95% CI =
      1.02-3.75) and psychiatric treatment history (OR = 2.58; 95% CI = 1.53-4.36) were
      predictors for psychiatric hospitalization. Of 258 patients followed for 2 years,
      10 (3.9%) died (3 suicide), and 24 (9.3%) undertook new suicide attempts.
      Patients with a history of psychiatric treatment had higher risks of new suicide
      attempts (OR = 2.46, 95% CI = 1.07-5.65). Suicide attempters admitted to
      emergency hospitals exhibit severe psychiatric disorders, and despite
      interventions, they continue to present high risks for suicide attempts and
      death. 

PMID- 25961845
TI  - Selective Allosteric Inhibition of MMP9 Is Efficacious in Preclinical Models of
      Ulcerative Colitis and Colorectal Cancer.
AB  - Expression of matrix metalloproteinase 9 (MMP9) is elevated in a variety of
      inflammatory and oncology indications, including ulcerative colitis and
      colorectal cancer. MMP9 is a downstream effector and an upstream mediator of
      pathways involved in growth and inflammation, and has long been viewed as a
      promising therapeutic target. However, previous efforts to target matrix
      metalloproteinases (MMPs), including MMP9, have utilized broad-spectrum or semi
      selective inhibitors. While some of these drugs showed signs of efficacy in
      patients, all MMP-targeted inhibitors have been hampered by dose-limiting
      toxicity or insufficient clinical benefit, likely due to their lack of
      specificity. Here, we show that selective inhibition of MMP9 did not induce
      musculoskeletal syndrome (a characteristic toxicity of pan-MMP inhibitors) in a
      rat model, but did reduce disease severity in a dextran sodium sulfate-induced
      mouse model of ulcerative colitis. We also found that MMP9 inhibition decreased
      tumor growth and metastases incidence in a surgical orthotopic xenograft model of
      colorectal carcinoma, and that inhibition of either tumor- or stroma-derived MMP9
      was sufficient to reduce primary tumor growth. Collectively, these data suggest
      that selective MMP9 inhibition is a promising therapeutic strategy for treatment
      of inflammatory and oncology indications in which MMP9 is upregulated and is
      associated with disease pathology, such as ulcerative colitis and colorectal
      cancer. In addition, we report the development of a potent and highly selective
      allosteric MMP9 inhibitor, the humanized monoclonal antibody GS-5745, which can
      be used to evaluate the therapeutic potential of MMP9 inhibition in patients. 

PMID- 25961848
TI  - Correction: Estimating the global burden of endemic canine rabies.

PMID- 25961849
TI  - Programmed Speed Reduction Enables Aortic Valve Opening and Increased Pulsatility
      in the LVAD-Assisted Heart.
AB  - Aortic valve opening (AVO) during left ventricular assist device (LVAD) support
      aids in preventing valve fusion, incompetence, and thrombosis. The programmed low
      speed algorithm (PLSA) allows AVO intermittently by reducing continuous motor
      speed during a dwell time. AVO and hemodynamics in the LVAD-assisted heart were
      measured using a HeartMate II (Thoratec Corporation, Pleasanton, CA) LVAD with a
      PLSA controller in a mock circulatory loop. Left ventricle and aortic pressures,
      LVAD, and total aortic flow were measured during pre-LVAD, non-PLSA and PLSA
      combinations of cardiac function, and LVAD speed. The low cardiac setting
      corresponded to a pre-LVAD cardiac output of 2.8 L/min, stroke volume of 40 ml,
      and ejection fraction of 22%; the medium setting produced values of 3.5 L/min, 50
      ml, and 28%, respectively. Results show that the PLSA controller set at 10 krpm,
      dropping to 7 krpm for dwell time of 6 s, adequately produced AVO for all tested
      cardiac functions with only minimal changes in cardiac output. However, AVO
      frequency was independent of opening area and systolic duration, which both
      decreased with increasing LVAD support. Furthermore, aortic pulsatility index
      quadrupled in the aortic root and doubled in the distal aorta during PLSA
      conditions, providing evidence that AVO and blood mixing are enabled by PLSA
      control at the appropriate speed. 

PMID- 25961850
TI  - Analysis of biofilm formation by intestinal lactobacilli.
AB  - In this study, the biofilm-forming potential of intestinal Lactobacillus reuteri
      strains under different culture conditions was characterized by microtiter plate
      biofilm assays. Moreover, the spatial organization of exogenously applied L.
      reuteri L2/6 (a pig isolate) at specific locations in gastrointestinal tract of
      monoassociated mice was investigated by fluorescence in situ hybridization. We
      did not detect biofilm formation by tested strains in nutrient-rich de Man-Rogosa
      Sharpe (MRS) medium. On the contrary, a highly positive biofilm formation was
      observed in medium with lower accessibility to the carbon sources and lack of
      salts. The results obtained confirmed the significant role of Tween 80 and the
      quantity and nature of the sugars in the growth medium in biofilm formation. The
      omission of Tween 80 in MRS medium favored the formation of biofilm. Abundant
      biofilm formation was detected in the presence of lactose, galactose, and
      glucose. However, a gradual increase in sugar concentration triggered a
      significant decrease in biofilm formation. In addition, conditions related to the
      gastrointestinal environment, such as low pH and the presence of bile and mucins,
      highly modulated biofilm production. This effect seems to be dependent on the
      specificity and properties of the medium used for cultivation. From the evidence
      provided by this study we conclude that the biofilm formation capacity of L.
      reuteri is strongly dependent on the environmental factors and culture medium
      used. 

PMID- 25961851
TI  - Improving survey response rates from parents in school-based research using a
      multi-level approach.
AB  - BACKGROUND: While schools can provide a comprehensive sampling frame for
      community-based studies of children and their families, recruitment is
      challenging. Multi-level approaches which engage multiple school stakeholders
      have been recommended but few studies have documented their effects. This paper
      compares the impact of a standard versus enhanced engagement approach on multiple
      indicators of recruitment: parent response rates, response times, reminders
      required and sample characteristics. METHODS: Parents and teachers were
      distributed a brief screening questionnaire as a first step for recruitment to a
      longitudinal study, with two cohorts recruited in consecutive years (cohort 1
      2011, cohort 2 2012). For cohort 2, additional engagement strategies included the
      use of pre-notification postcards, improved study materials, and recruitment
      progress graphs provided to school staff. Chi-square and t-tests were used to
      examine cohort differences. RESULTS: Compared to cohort 1, a higher proportion of
      cohort 2 parents responded to the survey (76% versus 69%; p < 0.001), consented
      to participate (71% versus 56%; p < 0.001), agreed to teacher participation (90%
      versus 82%; p < 0.001) and agreed to follow-up contact (91% versus 80%; p <
      0.001). Fewer cohort 2 parents required reminders (52% versus 63%; p < 0.001),
      and cohort 2 parents responded more promptly than cohort 1 parents (mean
      difference: 19.4 days, 95% CI: 18.0 to 20.9, p < 0.001). CONCLUSION: These
      results illustrate the value of investing in a relatively simple multi-level
      strategy to maximise parent response rates, and potentially reduce recruitment
      time and costs.

PMID- 25961852
TI  - Congenital generalized hypertrichosis terminalis: a proposed classification and a
      plea to avoid the ambiguous term "Ambras syndrome".
AB  - Congenital generalized hypertrichosis terminalis (CGHT) is a heterogenous group
      of diseases with continuing excessive growth of terminal hair. "Ambras syndrome"
      was first coined by Baumeister in 1993 to describe a case of nonsyndromic CGHT
      which was erroneously analogized to the portrait paintings of Petrus Gonzales and
      his children, exhibited in Ambras Castle near Innsbruck, Austria. This family
      probably, a syndromic type with abnormal dentition, inherited as an autosomal
      dominant trait. CGHT associated with gingival hyperplasia is probably a
      particular entity typified by the historical cases of Julia Pastrana and her son.
      An X-linked type of CGHT has likewise been categorized as "Ambras syndrome".
      Moreover, some reports have mistakenly classified "Ambras syndrome" as an example
      of hypertrichosis lanuginosa. Potential gene loci identified so far may include
      8q22, 17q24.2-q24.3 and Xq24-q27.1. The designation "Ambras syndrome" has thus
      been applied to various types of congenital hypertrichosis that differ to such
      degree that the name "Ambras" has no specific meaning, neither in the past nor in
      the future. Hence, this misleading term should now be jettisoned.

PMID- 25961853
TI  - Pharmacophore modeling for anti-Chagas drug design using the fragment molecular
      orbital method.
AB  - BACKGROUND: Chagas disease, caused by the parasite Trypanosoma cruzi, is a
      neglected tropical disease that causes severe human health problems. To develop a
      new chemotherapeutic agent for the treatment of Chagas disease, we predicted a
      pharmacophore model for T. cruzi dihydroorotate dehydrogenase (TcDHODH) by
      fragment molecular orbital (FMO) calculation for orotate, oxonate, and 43 orotate
      derivatives. METHODOLOGY/PRINCIPAL FINDINGS: Intermolecular interactions in the
      complexes of TcDHODH with orotate, oxonate, and 43 orotate derivatives were
      analyzed by FMO calculation at the MP2/6-31G level. The results indicated that
      the orotate moiety, which is the base fragment of these compounds, interacts with
      the Lys43, Asn67, and Asn194 residues of TcDHODH and the cofactor flavin
      mononucleotide (FMN), whereas functional groups introduced at the orotate 5
      position strongly interact with the Lys214 residue. CONCLUSIONS/SIGNIFICANCE: FMO
      based interaction energy analyses revealed a pharmacophore model for TcDHODH
      inhibitor. Hydrogen bond acceptor pharmacophores correspond to Lys43 and Lys214,
      hydrogen bond donor and acceptor pharmacophores correspond to Asn67 and Asn194,
      and the aromatic ring pharmacophore corresponds to FMN, which shows important
      characteristics of compounds that inhibit TcDHODH. In addition, the Lys214
      residue is not conserved between TcDHODH and human DHODH. Our analysis suggests
      that these orotate derivatives should preferentially bind to TcDHODH, increasing
      their selectivity. Our results obtained by pharmacophore modeling provides
      insight into the structural requirements for the design of TcDHODH inhibitors and
      their development as new anti-Chagas drugs.

PMID- 25961854
TI  - A novel screening method to assess developability of antibody-like molecules.
AB  - Monoclonal antibodies and antibody-like molecules represent a fast-growing class
      of bio-therapeutics that has rapidly transformed patient care in a variety of
      disease indications. The discovery of antibodies that bind to particular targets
      with high affinity is now a routine exercise and a variety of in vitro and in
      vivo techniques are available for this purpose. However, it is still challenging
      to identify antibodies that, in addition to having the desired biological effect,
      also express well, remain soluble at different pH levels, remain stable at high
      concentrations, can withstand high shear stress, and have minimal non-specific
      interactions. Many promising antibody programs have ultimately failed in
      development due to the problems associated with one of these factors. Here, we
      present a simple high-performance liquid chromatography (HPLC)-based screening
      method to assess these developability factors earlier in discovery process. This
      method is robust and requires only microgram quantities of proteins. Briefly, we
      show that for antibodies injected on a commercially available pre-packed Zenix
      HPLC column, the retention times are inversely related to their colloidal
      stability with antibodies prone to precipitation or aggregation retained longer
      on the column with broader peaks. By simply varying the salt content of running
      buffer, we were also able to estimate the nature of interactions between the
      antibodies and the column. We believe this approach should generally be
      applicable to assessment of the developability of other classes of bio
      therapeutic molecules, and that the addition of this simple tool early in the
      discovery process will lead to selection of molecules with improved
      developability characteristics. 

PMID- 25961855
TI  - Sexual and Reproductive Health Indicators and Intimate Partner Violence
      Victimization Among Female Family Planning Clinic Patients Who Have Sex with
      Women and Men.
AB  - BACKGROUND: Sexual minority women are more likely than heterosexual women to have
      ever experienced intimate partner violence (IPV). Although IPV is associated with
      sexual risk and poor reproductive health outcomes among US women overall, little
      is known about whether IPV is related to sexual and reproductive health
      indicators among sexual minority women in particular. METHODS: Baseline data from
      a prospective intervention trial were collected from women ages 16-29 years at 24
      family planning clinics in western PA (n=3,455). Multivariable logistic
      regression for clustered survey data was used to compare women who have sex with
      men only (WSM) and women who have sex with women and men (WSWM) on (1) IPV
      prevalence and (2) sexual and reproductive health behaviors, outcomes, and
      services use, controlling for IPV. Finally, we tested the interaction of sexual
      minority status and IPV. RESULTS: WSWM were significantly more likely than WSM to
      report a lifetime history of IPV (adjusted odds ratio (AOR): 3.00; 95% confidence
      interval (CI): 2.30, 3.09). Controlling for IPV, WSWM reported higher levels of
      sexual risk behaviors (e.g., unprotected vaginal and anal sex), male-perpetrated
      reproductive coercion, unwanted pregnancy, and sexually transmitted infection
      (STI) and pregnancy testing but less contraceptive care seeking. The association
      between IPV and lifetime STI diagnosis was greater among WSWM than among WSM.
      CONCLUSIONS: IPV was pervasive and associated with sexual risk and reproductive
      health indicators among WSWM in this clinic-based setting. Healthcare providers'
      sexual risk assessment and provision of sexual and reproductive health services
      should be informed by an understanding of women's sexual histories, including sex
      of sexual partners and IPV history, in order to help ensure that all women
      receive the clinical care they need.

PMID- 25961856
TI  - Googling Stroke ASPECTS to Determine Disability: Exploratory Analysis from VISTA
      Acute Collaboration.
AB  - The summed Alberta Stroke Program Early CT Score (ASPECTS) is useful for
      predicting stroke outcome. The anatomical information in the CT template is
      rarely used for this purpose because traditional regression methods are not adept
      at handling collinearity (relatedness) among brain regions. While penalized
      logistic regression (PLR) can handle collinearity, it does not provide an
      intuitive understanding of the interaction among network structures in a way that
      eigenvector method such as PageRank can (used in Google search engine). In this
      exploratory analysis we applied graph theoretical analysis to explore the
      relationship among ASPECTS regions with respect to disability outcome. The
      Virtual International Stroke Trials Archive (VISTA) was searched for patients who
      had infarct in at least one ASPECTS region (ASPECTS <= 9, ASPECTS = 10 were
      excluded), and disability (modified Rankin score/mRS). A directed graph was
      created from a cross correlation matrix (thresholded at false discovery rate of
      0.01) of the ASPECTS regions and demographic variables and disability (mRS > 2).
      We estimated the network-based importance of each ASPECTS region by comparing
      PageRank and node strength measures. These results were compared with those from
      PLR. There were 185 subjects, average age 67.5 +/- 12.8 years (55% Males). Model
      1: demographic variables having no direct connection with disability, the highest
      PageRank was M2 (0.225, bootstrap 95% CI 0.215-0.347). Model 2: demographic
      variables having direct connection with disability, the highest PageRank were M2
      (0.205, bootstrap 95% CI 0.194-0.367) and M5 (0.125, bootstrap 95% CI 0.096
      0.204). Both models illustrate the importance of M2 region to disability. The
      PageRank method reveals complex interaction among ASPECTS regions with respects
      to disability. This approach may help to understand the infarcted brain network
      involved in stroke disability.

PMID- 25961858
TI  - The effect of shear flow on nanoparticle agglomeration and deposition in in vitro
      dynamic flow models.
AB  - Traditional in vitro toxicity experiments typically involve exposure of a mono-
      or co-culture of cells to nanoparticles (NPs) in static conditions with the
      assumption of 100% deposition (i.e. dose) of well-dispersed particles. However,
      cellular dose can be affected by agglomeration and the unique transport kinetics
      of NPs in biological media. We hypothesize that shear flow can address these
      issues and achieve more predictable dosage. Here, we compare the behavior of gold
      NPs with diameters of 5, 10 and 30 nm in static and dynamic in vitro models. We
      also utilize transport modeling to approximate the shear rate experienced by the
      cells in dynamic conditions to evaluate physiological relevance. The transport
      kinetics show that NP behavior is governed by both gravity and diffusion forces
      in static conditions and only diffusion in dynamic conditions. Our results reveal
      that dynamic systems are capable of producing a more predictable dose compared to
      static systems, which has strong implications for improving repeatability in
      nanotoxicity assessments. 

PMID- 25961857
TI  - A physiologically based pharmacokinetic model for polyethylene glycol-coated gold
      nanoparticles of different sizes in adult mice.
AB  - Nanoparticles (NPs) are widely used in various fields of nanomedicine. A
      systematic understanding of NP pharmacokinetics is crucial in their design,
      applications, and risk assessment. In order to integrate available experimental
      information and to gain insights into NP pharmacokinetics, a membrane-limited
      physiologically based pharmacokinetic (PBPK) model for polyethylene glycol-coated
      gold (Au) NPs (PEG-coated AuNPs) was developed in mice. The model described
      endocytosis of the NPs in the liver, spleen, kidneys, and lungs and was
      calibrated using data from mice that were intravenously injected with 0.85 mg/kg
      13 nm and 100 nm PEG-coated AuNPs. The model adequately predicted multiple
      external datasets for PEG-coated AuNPs of similar sizes (13-20 nm; 80-100 nm),
      indicating reliable predictive capability in suitable size ranges. Simulation
      results suggest that endocytosis of NPs is time and size dependent, i.e.
      endocytosis of larger NPs occurs immediately and predominately from the blood,
      whereas smaller NPs can diffuse through the capillary wall and their endocytosis
      appears mainly from the tissue with a 10-h delay, which may be the primary
      mechanism responsible for the reported size-dependent pharmacokinetics of NPs.
      Several physiological parameters (e.g. liver weight fraction of body weight) were
      identified to have a high influence on selected key dose metrics, indicating the
      need for additional interspecies comparison and scaling studies and to conduct
      pharmacokinetic studies of NPs in species that are more closely related to humans
      in these parameters. This PBPK model provides useful insights into the size,
      time, and species dependence of NP pharmacokinetics.

PMID- 25961859
TI  - What It Takes to Be a Pseudomonas aeruginosa? The Core Genome of the
      Opportunistic Pathogen Updated.
AB  - Pseudomonas aeruginosa is an opportunistic bacterial pathogen able to thrive in
      highly diverse ecological niches and to infect compromised patients. Its genome
      exhibits a mosaic structure composed of a core genome into which accessory genes
      are inserted en bloc at specific sites. The size and the content of the core
      genome are open for debate as their estimation depends on the set of genomes
      considered and the pipeline of gene detection and clustering. Here, we redefined
      the size and the content of the core genome of P. aeruginosa from fully re
      analyzed genomes of 17 reference strains. After the optimization of gene
      detection and clustering parameters, the core genome was defined at 5,233
      orthologs, which represented ~ 88% of the average genome. Extrapolation indicated
      that our panel was suitable to estimate the core genome that will remain constant
      even if new genomes are added. The core genome contained resistance determinants
      to the major antibiotic families as well as most metabolic, respiratory, and
      virulence genes. Although some virulence genes were accessory, they often related
      to conserved biological functions. Long-standing prophage elements were subjected
      to a genetic drift to eventually display a G+C content as higher as that of the
      core genome. This contrasts with the low G+C content of highly conserved
      ribosomal genes. The conservation of metabolic and respiratory genes could
      guarantee the ability of the species to thrive on a variety of carbon sources for
      energy in aerobiosis and anaerobiosis. Virtually all the strains, of
      environmental or clinical origin, have the complete toolkit to become resistant
      to the major antipseudomonal compounds and possess basic pathogenic mechanisms to
      infect humans. The knowledge of the genes shared by the majority of the P.
      aeruginosa isolates is a prerequisite for designing effective therapeutics to
      combat the wide variety of human infections. 

PMID- 25961860
TI  - MiRduplexSVM: A High-Performing MiRNA-Duplex Prediction and Evaluation
      Methodology.
AB  - We address the problem of predicting the position of a miRNA duplex on a microRNA
      hairpin via the development and application of a novel SVM-based methodology. Our
      method combines a unique problem representation and an unbiased optimization
      protocol to learn from mirBase19.0 an accurate predictive model, termed
      MiRduplexSVM. This is the first model that provides precise information about all
      four ends of the miRNA duplex. We show that (a) our method outperforms four state
      of-the-art tools, namely MaturePred, MiRPara, MatureBayes, MiRdup as well as a
      Simple Geometric Locator when applied on the same training datasets employed for
      each tool and evaluated on a common blind test set. (b) In all comparisons,
      MiRduplexSVM shows superior performance, achieving up to a 60% increase in
      prediction accuracy for mammalian hairpins and can generalize very well on plant
      hairpins, without any special optimization. (c) The tool has a number of
      important applications such as the ability to accurately predict the miRNA or the
      miRNA*, given the opposite strand of a duplex. Its performance on this task is
      superior to the 2nts overhang rule commonly used in computational studies and
      similar to that of a comparative genomic approach, without the need for prior
      knowledge or the complexity of performing multiple alignments. Finally, it is
      able to evaluate novel, potential miRNAs found either computationally or
      experimentally. In relation with recent confidence evaluation methods used in
      miRBase, MiRduplexSVM was successful in identifying high confidence potential
      miRNAs. 

PMID- 25961861
TI  - Veteran PTSS and spouse relationship quality: The importance of dyadic coping.
AB  - Research with combat veterans and their spouses has documented the harmful impact
      of posttraumatic stress symptoms (PTSS) on relationships, yet few studies have
      evaluated theoretically based models of relational processes among these couples.
      In this study, the authors tested 2 moderators of the association between male
      combat veterans' PTSS and their female spouses' reported relationship quality
      based on Bodenmann's (1997, 2005) systemic transactional theory of dyadic coping.
      We hypothesized that supportive dyadic coping and common dyadic coping would
      moderate the association of PTSS and spouses' relationship quality. Hypotheses
      were supported. The degree to which a veteran's PTSS was negatively associated
      with his spouse's relationship quality depended on whether she perceived him as
      supportive when she experiences stress (i.e., supportive dyadic coping) and the
      degree to which she perceived the couple as working together to manage
      difficulties (i.e., common dyadic coping). The significant interactions of PTSS
      with supportive and common dyadic coping accounted for 11.95% and 10.58% of the
      variance, respectively. Tests of conditional effects showed veterans' PTSS was
      only significantly negatively associated with spouses' relationship quality when
      supportive and common dyadic coping were low. Findings highlight the importance
      of adaptive dyadic coping behaviors as a protective factor for spouses of
      veterans and hold implications for research and practice.

PMID- 25961862
TI  - A cross-cultural longitudinal examination of the effect of cumulative adversity
      on the mental and physical health of older adults.
AB  - Self-oriented adversity refers to traumatic events that primarily inflict the
      self, whereas other-oriented adversity refers to events that affect the self by
      primarily targeting others. The present study aimed to examine whether cultural
      background moderates the effects of self-oriented and other-oriented adversity on
      mental and physical health of older adults. Using longitudinal data from the
      Israeli component of the Survey of Health and Retirement, we focused on 370 Jews
      and 239 Arabs who reported their exposure to various adversities across the life
      span, and completed questionnaires regarding mental and physical health. Results
      showed that the effect of self-oriented adversity on health did not differ among
      Jews and Arabs. However, other-oriented adversity showed a stronger effect on
      Arabs' mental and physical health than on Jews' health. Our findings suggest that
      the accumulation of adverse events that affect the self by primarily targeting
      others may have a stronger impact in collectivist cultures than in individualist
      cultures.

PMID- 25961863
TI  - Anger intensification with combat-related PTSD and depression comorbidity.
AB  - Anger is becoming more widely recognized for its involvement in the psychological
      adjustment problems of current war veterans. Recent research with combat veterans
      has found anger to be related to psychological distress, psychosocial
      functioning, and harm risk variables. Using behavioral health data for 2,077
      treatment-seeking soldiers who had been deployed to Iraq and Afghanistan, this
      study examined whether anger disposition was intensified for those who met screen
      threshold criteria for posttraumatic stress disorder (PTSD) and major depressive
      disorder (MDD). Anger was assessed with a 7-item screening measure previously
      validated with the study population. The study tested the hypothesis that anger
      would be highest when "PTSD & MDD" were conjoined, compared with "PTSD only,"
      "MDD only," and "no PTSD, no MDD." PTSD and depression were assessed with well
      established screening instruments. A self-rated "wanting to harm others" variable
      was also incorporated. Age, gender, race, military component, military grade, and
      military unit social support served as covariates. Hierarchical multiple
      regression was used to test the hypothesis, which was confirmed. Anger was
      intensified in the PTSD & MDD condition, in which it was significantly higher
      than in the other 3 conditions. Convergent support was obtained for "wanting to
      harm others" as an exploratory index. Given the high prevalence and co-occurrence
      of PTSD and MDD among veterans, the results have research and clinical practice
      relevance for systematic inclusion of anger assessment postdeployment from risk
      assessment and screening standpoints.

PMID- 25961864
TI  - Feelings of wantedness and consent during nonconsensual sex: Implications for
      posttraumatic cognitions.
AB  - Social-cognitive models of traumatic stress have urged researchers to investigate
      the complex changes in victims' systems of belief following trauma. Among victims
      of rape, posttraumatic cognitions related to self-blame, safety, trust, intimacy,
      control, power, and esteem are common negative outcomes; yet there is great
      variability in the degree to which rape victims exhibit these reactions, and this
      remains unexplained. Two possible factors that may be relevant to the development
      of these posttraumatic cognitions are the extent to which the nonconsensual
      sexual act was internally perceived as nonconsensual by the victim and the extent
      to which it was internally perceived as unwanted by the victim. Although felt
      consent and perceived wanting are often conflated and rated dichotomously, there
      is evidence that they are distinct and may be experienced on a continuum. This
      study sought to examine the relationships among felt consent, wantedness, and
      posttraumatic cognitions in a sample of 189 undergraduate female victims of rape.
      Results demonstrated that perceived consent and perceived wantedness had unique
      and opposite relationships with posttraumatic cognitions: Greater felt consent
      was a risk factor for characterological and behavioral self-blame and maladaptive
      self-beliefs, but greater feelings of wanting to have sex constituted a
      protective factor for characterological self-blame, maladaptive self-beliefs, and
      maladaptive world-beliefs. A suppression effect was also identified, which
      provided evidence that perceived consent and wantedness work in tandem in the
      cognitive processing of rape. Clinical and research implications are discussed,
      with an emphasis on the importance of understanding and honoring victims'
      perceptions.

PMID- 25961865
TI  - Delivering cognitive processing therapy in a community health setting: The
      influence of Latino culture and community violence on posttraumatic cognitions.
AB  - Despite the applicability of cognitive processing therapy (CPT) for posttraumatic
      stress disorder (PTSD) to addressing sequelae of a range of traumatic events, few
      studies have evaluated whether the treatment itself is applicable across diverse
      populations. The present study examined differences and similarities among non
      Latino, Latino Spanish-speaking, and Latino English-speaking clients in rigid
      beliefs-or "stuck points"-associated with PTSD symptoms in a sample of community
      mental health clients. We utilized the procedures of content analysis to analyze
      stuck point logs and impact statements of 29 participants enrolled in a larger
      implementation trial for CPT. Findings indicated that the content of stuck points
      was similar across Latino and non-Latino clients, although fewer total stuck
      points were identified for Latino clients compared to non-Latino clients. Given
      that identification of stuck points is central to implementing CPT, difficulty
      identifying stuck points could pose significant challenges for implementing CPT
      among Latino clients and warrants further examination. Thematic analysis of
      impact statements revealed the importance of family, religion, and the urban
      context (e.g., poverty, violence exposure) in understanding how clients organize
      beliefs and emotions associated with trauma. Clinical recommendations for
      implementing CPT in community settings and the identification of stuck points are
      provided.

PMID- 25961866
TI  - The influence of trait-negative affect and compassion satisfaction on compassion
      fatigue in Australian nurses.
AB  - For this study, we examined the nature of the unique relationships trait-negative
      affect and compassion satisfaction had with compassion fatigue and its components
      of secondary traumatic stress and burnout in 273 nurses from 1 metropolitan
      tertiary acute hospital in Western Australia. Participants completed the
      Professional Quality of Life Scale (Stamm, 2010), Depression Anxiety Stress Scale
      (Lovibond & Lovibond, 2004), and the State-Trait Anxiety Inventory (Spielberger,
      Gorsuch, Lushene, Vagg, & Jacobs, 1983). Bivariate correlation and hierarchical
      regression analyses were performed to examine and investigate 4 hypotheses. The
      results demonstrate a clear differential pattern of relationships with secondary
      traumatic stress and burnout for both trait-negative affect and compassion
      satisfaction. Trait-negative affect was clearly the more important factor in
      terms of its contribution to overall compassion fatigue and secondary traumatic
      stress. In contrast, compassion satisfaction's unique protective relationship
      only related to burnout, and not secondary traumatic stress. The results are
      therefore consistent with the view that compassion satisfaction may be an
      important internal resource that protects against burnout, but is not directly
      influential in protecting against secondary traumatic stress for nurses working
      in an acute-care hospital environment. With the projected nursing workforce
      shortages in Australia, it is apparent that a further understanding is warranted
      of how such personal variables may work as protective and risk factors.

PMID- 25961867
TI  - A meta-analytic review of overgeneral memory: The role of trauma history, mood,
      and the presence of posttraumatic stress disorder.
AB  - A number of studies suggest that a history of trauma, depression, and
      posttraumatic stress disorder (PTSD) are associated with autobiographical memory
      deficits, notably overgeneral memory (OGM). However, whether there are any group
      differences in the nature and magnitude of OGM has not been evaluated. Thus, a
      meta-analysis was conducted to quantify group differences in OGM. The effect
      sizes were pooled from studies examining the effect on OGM from a history of
      trauma (e.g., childhood sexual abuse), and the presence of PTSD or current
      depression (e.g., major depressive disorder). Using multiple search engines, 13
      trauma studies and 12 depression studies were included in this review. A
      depression effect was observed on OGM with a large effect size, and was more
      evident by the lack of specific memories, especially to positive cues. An effect
      of trauma history on OGM was observed with a medium effect size, and this was
      most evident by the presence of overgeneral responses to negative cues. The
      results also suggested an amplified memory deficit in the presence of PTSD. That
      is, the effect sizes of OGM among individuals with PTSD were very large and
      relatively equal across different types of OGM. Future studies that directly
      compare the differences of OGM among 4 samples (i.e., controls, current
      depression without trauma history, trauma history without depression, and trauma
      history and depression) would be warranted to verify the current findings.

PMID- 25961868
TI  - Narratives of traumatic birth: Quality and changes over time.
AB  - Childbirth is a highly emotive event that can involve complications. Around 1% of
      births in the United Kingdom involve life-threatening complications to the mother
      (Waterstone, Bewley, & Wolfe, 2001) and 0.8% result in stillbirth or perinatal
      death (Confidential Enquiry into Maternal and Child Health [CEMACH], 2009). A
      review found that 3.1% of women report posttraumatic stress disorder (PTSD) after
      birth (Grekin & O'Hara, 2014). The aim of this study was to examine whether
      narrative characteristics of traumatic birth were specific to women with PTSD or
      observed in all women who experience a highly emotive and potentially traumatic
      birth. Parturient women were matched for birth events, but either had severe PTSD
      symptoms (n = 22) or no, or very low, PTSD symptoms (n = 22). Women were
      interviewed about the birth 3 and 6 months postpartum, and their birth narratives
      were examined for content, coherence, and cognitive and perceptual processing.
      Results showed birth narratives became shorter and more coherent over time.
      Consistent with PTSD literature, birth memories were more likely to be recalled
      and involuntarily triggered in women with PTSD symptoms. However, women with PTSD
      symptoms had more coherent narratives, used more causal and fewer tentative
      words. These latter findings are inconsistent with research finding that PTSD is
      associated with fragmented or incoherent memories but are consistent with the
      view that highly emotive events result in improved memory (e.g., Berntsen,
      Willert, & Rubin, 2003). Possible reasons for this are discussed.

PMID- 25961870
TI  - Mandibular Ridge Augmentation Using a Mineralized Ilium Block: A Case Letter.

PMID- 25961869
TI  - Cumulative burden of lifetime adversities: Trauma and mental health in low-SES
      African Americans and Latino/as.
AB  - This study examined the utility of a lifetime cumulative adversities and trauma
      model in predicting the severity of mental health symptoms of depression,
      anxiety, and posttraumatic stress disorder. We also tested whether ethnicity and
      gender moderate the effects of this stress exposure construct on mental health
      using multigroup structural equation modeling. A sample of 500 low-socioeconomic
      status African American and Latino men and women with histories of adversities
      and trauma were recruited and assessed with a standard battery of self-report
      measures of stress and mental health. Multiple-group structural equation models
      indicated good overall model fit. As hypothesized, experiences of discrimination,
      childhood family adversities, childhood sexual abuse, other childhood trauma, and
      chronic stresses all loaded on the latent cumulative burden of adversities and
      trauma construct (CBAT). The CBAT stress exposure index in turn predicted the
      mental health status latent variable. Although there were several significant
      univariate ethnic and gender differences, and ethnic and gender differences were
      observed on several paths, there were no significant ethnic differences in the
      final model fit of the data. These findings highlight the deleterious
      consequences of cumulative stress and trauma for mental health and underscore a
      need to assess these constructs in selecting appropriate clinical interventions
      for reducing mental health disparities and improving human health.

PMID- 25961871
TI  - Classroom norms of bullying alter the degree to which children defend in response
      to their affective empathy and power.
AB  - This study examined whether the degree to which bullying is normative in the
      classroom would moderate associations between intra- (cognitive and affective
      empathy, self-efficacy beliefs) and interpersonal (popularity) factors and
      defending behavior. Participants were 6,708 third- to fifth-grade children (49%
      boys; Mage = 11 years) from 383 classrooms. Multilevel modeling analyses revealed
      that children were more likely to defend in response to their affective empathy
      in classrooms with high levels of bullying. In addition, popular students were
      more likely to support victims in classrooms where bullying was associated with
      social costs. These findings highlight the importance of considering interactions
      among individual and contextual influences when trying to understand which
      factors facilitate versus inhibit children's inclinations to defend others.

PMID- 25961872
TI  - When crizotinib-induced bradycardia becomes symptomatic: role of concomitant
      drugs.
AB  - Crizotinib is an orally active multi-target tyrosine kinase inhibitor which is
      the standard of care in patients with anaplastic lymphoma kinase translocated non
      small-cell lung cancer. Common adverse events in clinical trials with crizotinib
      included visual disorders, nausea-vomiting, diarrhea and elevated transaminases.
      Less common toxicities are emerging, such as bradycardia and QT interval
      prolongation. We report on a case of a presyncopal episode which occurred under
      crizotinib and metoclopramide treatment. 

PMID- 25961873
TI  - Age-Related Increase of EED Expression in Early Hematopoietic Progenitor Cells is
      Associated with Global Increase of the Histone Modification H3K27me3.
AB  - Human hematopoietic stem and progenitor cells (HSPCs) from umbilical cord blood
      exhibit higher differentiation potential and repopulation capacity compared to
      adult HSPCs. The molecular basis for these functional differences is currently
      unknown. Upon screening for epigenetic effector genes being differentially
      expressed in neonatal and adult HSPC subpopulations, the Polycomb Repressive
      Complex 2 (PRC2) member EED was identified. Even though EED is expressed at
      comparable amounts in neonatal and adult multipotent HSPCs, early adult lineage
      committed progenitors of the lymphomyeloid (LM) and erythromyeloid lineages
      expressed higher EED amounts than neonatal HPCs. We demonstrate that EED
      overexpression directly leads to higher H3K27me3 levels, a repressive histone
      modification that is mediated by the PRC2 complex. Quantitative analysis of
      H3K27me3 levels by FPLC-based ELISA revealed elevated levels in primary blood
      cells from adults. Besides quantitative changes, gene ontology analysis of the
      genome-wide H3K27me3 distribution revealed qualitative changes in adult HSPCs
      with elevated levels in genes associated with nonhematopoietic development
      pathways. In contrast, H3K4me3 which labels active chromatin was enriched on
      hematopoietic genes. In vitro differentiation of EED-transfected neonatal HSPCs
      revealed aberrant expression of the myelopoietic marker CD14, suggesting that EED
      affects the lymphoid versus myeloid decision processes within the lymphomyeloid
      lineage. This is in line with LM progenitors having the most pronounced
      differences in EED expression. Highlighting the dynamic roles of epigenetic
      modifications in human hematopoiesis, the present data demonstrate shifts in the
      PRC2-associated histone modification H3K27me3 from birth to adulthood. 

PMID- 25961874
TI  - Associations of a Short Sleep Duration, Insufficient Sleep, and Insomnia with
      Self-Rated Health among Nurses.
AB  - Epidemiological evidence suggests that sleep duration and poor sleep are
      associated with mortality, as well as with a wide range of negative health
      outcomes. However, few studies have examined the association between sleep and
      self-rated health, particularly through the combination of sleep complaints. The
      objective of this study was to examine whether self-rated health is associated
      with sleep complaints, considering the combination of sleep duration, insomnia,
      and sleep sufficiency. This cross-sectional study was performed in the 18 largest
      public hospitals in the city of Rio de Janeiro, Brazil. A total of 2518 female
      nurses answered a self-filled multidimensional questionnaire. The adjusted odds
      ratios and 95% confidence intervals (CIs) estimated the chance of poor self-rated
      health in the presence of different combinations of sleep duration and quality.
      Compared with women who reported adequate sleep duration with no sleep quality
      complaints (reference group), the odds ratios (95% CI) for poor self-rated health
      were 1.79 (1.27-2.24) for those who reported only insufficient sleep, 1.85 (0.94
      3.66) for only a short sleep duration, and 3.12 (1.94-5.01) for only insomnia.
      Compared with those who expressed all three complaints (short sleep duration,
      insomnia, and insufficient sleep), the odds ratio for poor self-rated health was
      4.49 (3.25-6.22). Differences in the magnitude of the associations were observed,
      depending on the combination of sleep complaints. Because self-rated health is a
      consistent predictor of morbidity, these results reinforce the increasing
      awareness of the role of sleep in health and disease. Our findings contribute to
      the recognition of sleep as a public health matter that deserves to be better
      understood and addressed by policymakers. 

PMID- 25961875
TI  - TOT phenomena: Gesture production in younger and older adults.
AB  - This study explored age-related changes in gesture to better understand the
      relationship between gesture and word retrieval from memory. The frequency of
      gestures during tip-of-the-tongue (TOT) states highlights this relationship.
      There is a lack of evidence describing the form and content of iconic gestures
      arising spontaneously in such TOT states and a parallel gap addressing age
      related variations. In this study, TOT states were induced in 45 participants
      from 2 age groups (older and younger adults) using a pseudoword paradigm. The
      type and frequency of gestures produced was recorded during 2 experimental
      conditions (single-word retrieval and narrative task). We found that both groups
      experienced a high number of TOT states, during which they gestured. Iconic co
      TOT gestures were more common than noniconic gestures. Although there was no age
      effect on the type of gestures produced, there was a significant, task-specific
      age difference in the amount of gesturing. That is, younger adults gestured more
      in the narrative task, whereas older adults generated more gestures in the single
      word-retrieval task. Task-specific age differences suggest that there are age
      related differences in terms of the cognitive operations involved in TOT gesture
      production.

PMID- 25961876
TI  - Cognitive aging in older Black and White persons.
AB  - During a mean of 5.2 years of annual follow-up, older Black (n = 647) and White
      (n = 647) persons of equivalent age and education completed a battery of 17
      cognitive tests from which composite measures of 5 abilities were derived.
      Baseline level of each ability was lower in the Black subgroup. Decline in
      episodic and working memory was not related to race. Decline in semantic memory,
      perceptual speed, and visuospatial ability was slower in Black persons than White
      persons, and in semantic memory and perceptual speed this effect was stronger in
      older than younger participants. Racial differences persisted after adjustment
      for retest effects. The results suggest subtle cognitive aging differences
      between Black persons and White persons.

PMID- 25961877
TI  - Identifying age-invariant and age-limited mechanisms for enhanced memory
      performance: Insights from self-referential processing in younger and older
      adults.
AB  - Self-referential processing has been identified as a possible tool for supporting
      effective encoding processes in the elderly population. However, the importance
      of self-reference per se, relative to the increase in meaningful elaboration
      normally associated with self-reference instructions, remains unclear. The
      present study sought to explore this issue further by examining self-referential
      encoding strategies that inherently involve more extensive stimulus elaboration:
      episodic autobiographical memory (AM) retrieval and semantic AM retrieval. These
      were compared with an analogous task involving retrieval of general semantic
      knowledge, as well as traditional binary self-referential and semantic encoding
      judgments. We found that both AM retrieval and general semantic retrieval at
      encoding resulted in substantial enhancements to recall and recognition memory of
      concrete nouns relative to binary encoding judgments across both age groups.
      Furthermore, older adults exhibited larger benefits from this additional
      elaboration than did younger adults, leading to elimination of age-related
      deficits in recognition memory. However, younger adults showed an additional
      boost to subsequent memory following episodic, relative to semantic, AM retrieval
      during free recall that was not exhibited by older adults. This may be because of
      greater demands on frontally mediated control processes and cognitive resources
      associated with the use of this strategy. Taken together, the results suggest
      that the mnemonic benefits associated with self-referential processing vary
      substantially depending on the specific nature of the encoding strategy, and
      suggest that, under certain conditions, semantic processing and self-referential
      processing are equally effective in mitigating age-related deficits in memory
      performance.

PMID- 25961878
TI  - Can DRYAD explain age-related associative memory deficits?
AB  - A recent interesting theoretical account of aging and memory judgments, the DRYAD
      (density of representations yields age-related deficits; Benjamin, 2010;
      Benjamin, Diaz, Matzen, & Johnson, 2012), attributes the extensive findings of
      disproportional age-related deficits in memory for source, context, and
      associations, to a global decline in memory fidelity. It is suggested that this
      global deficit, possibly due to a decline in attentional processes, is moderated
      by weak representation of contextual information to result in disproportional age
      related declines. In the current article, we evaluate the DRYAD model, comparing
      it to specific age-related deficits theories, in particular, the ADH (associative
      deficit hypothesis, Naveh-Benjamin, 2000). We question some of the main
      assumptions/hypotheses of DRYAD in light of data reported in the literature, and
      we directly assess the role of attention in age-related deficits by manipulations
      of divided attention and of the instructions regarding what to pay attention to
      in 2 experiments (one from the literature and a new one). The results of these
      experiments fit the predictions of the ADH and do not support the main
      assumption/hypotheses of DRYAD.

PMID- 25961879
TI  - Cognitive dedifferentiation with increasing age and proximity of death: Within
      person evidence from the Seattle Longitudinal Study.
AB  - A central aim of life-span psychology is to understand ontogenetic changes in the
      structure of individuals' actions, thoughts, and behaviors. The dedifferentiation
      hypothesis of cognitive aging suggests that the structure of individuals'
      cognitive abilities becomes less differentiated in old age. Empirical tests have
      almost exclusively approached this hypothesis from a between-person difference
      perspective and produced a mixed set of findings. In the present study, we pursue
      a within-person test of the hypothesis using up to 8 repeated measures of
      cognitive abilities over up to 49 years, covering fluid (inductive reasoning),
      visualization (spatial orientation), and crystallized abilities (number, verbal
      meaning, and word fluency), obtained from 419 now-deceased individuals who
      participated in the Seattle Longitudinal Study (SLS) and have provided at least 4
      observations for each cognitive test. Results revealed that with advancing age
      and proximity to death, within-person coupling increased (a) among the
      crystallized abilities, (b) between visualization and fluid abilities, (c)
      between visualization and crystallized abilities, and (d) between fluid abilities
      and crystallized abilities. We discuss the importance of within-person analyses
      for understanding changes in the structure of behavior and consider how our
      findings inform research on cognitive decline and dedifferentiation later in
      life.

PMID- 25961880
TI  - Loss of attentional inhibition in older adults--Does it really exist? An
      experimental dissociation of inhibitory and memory retrieval processes.
AB  - It is commonly assumed that attentional inhibitory functioning decreases with
      age, even though empirical evidence is mixed. These inconsistencies possibly stem
      from methodological artifacts: distractor inhibition is typically assessed with
      the negative priming paradigm, which confounds inhibition and episodic retrieval.
      In the present study, we investigated age differences in a sequential distractor
      repetition paradigm (Giesen, Frings, & Rothermund, 2012) that provides
      independent estimates of distractor inhibition and episodic retrieval processes.
      Older (60+ yrs) and younger (below 30 years) adults identified target letters
      that were flanked by distractors (JKJ). Inhibitory processes were preserved in
      older adults, who showed reliable distractor repetition benefits resulting from
      persistent distractor inhibition; however, a significant loss of inhibition was
      apparent for the older subgroup of participants (65+ yrs) compared with a
      subgroup of young-old participants (60 to 64 years). No age differences were
      found for episodic retrieval processes of stimulus-response bindings that were
      indexed by an interaction of distractor repetition and response relation.
      Findings highlight the importance of dissociating between distractor inhibition
      and retrieval processes that are differently implicated in age-related cognitive
      change.

PMID- 25961881
TI  - Changing predictors of self-rated health: Disentangling age and cohort effects.
AB  - Previous studies have shown that some predictors of self-rated health (SRH)
      become more important with age, while others become less important. Although
      based on cross-sectional data, these findings are often interpreted as age
      related changes in evaluation criteria. However, results could be due to cohort
      effects as well. We attempted to disentangle age and cohort effects by combining
      and comparing cross-sectional and longitudinal data from a large-scale
      longitudinal survey. The sample consisted of 2,982 community-dwelling
      participants from 2 measurement occasions of the German Ageing Survey ages 40-81
      years at baseline. Multigroup latent regression models were used to examine
      whether associations between various predictors and SRH differed between age
      groups and whether they changed over time. Comparisons of cross-sectional age
      differences in SRH-predictor associations and longitudinal age changes in the
      same associations allow the identification of cohort effects. Number of chronic
      conditions showed a constant negative association with SRH independently of age
      and cohort. In contrast, the association between SRH and all other predictors
      (physical functioning, exercise, life satisfaction, depressive symptoms, and
      positive affect) changed longitudinally, pointing to an age effect. Prediction of
      SRH by depressive symptoms and positive affect showed an additional cohort
      effect: The negative associations between depressive symptoms and SRH and the
      positive associations between positive affect and SRH were stronger among younger
      cohorts. The findings provide not only longitudinal support for previous cross
      sectional studies, but also show the impact of historical change: Emotional
      facets of psychological well-being increase in relevance for SRH across cohorts.

PMID- 25961882
TI  - Effect of Hydrophobic and Hydrophilic Surfaces on the Stability of Double
      Stranded DNA.
AB  - DNA hybridization is the foundation for numerous technologies like DNA origami
      and DNA sensing/microarrays. Using molecular simulations, enhanced-sampling
      methods, and free-energy calculations, we show the effects of hydrophilic and
      hydrophobic surfaces on DNA hybridization. Hydrophilic surfaces compete with
      terminal bases' H-bonds but stabilize central base stacking. Hydrophobic surfaces
      strengthen terminal H-bonds but destabilize central base stacking. Regardless of
      surface chemistry, for terminal bases, melting proceeds through breaking H-bonds,
      followed by unstacking from the neighboring base. For central bases in bulk or
      near hydrophobic surfaces, melting proceeds by disruption of H-bonds, followed by
      unstacking, whereas on hydrophilic surfaces, unstacking from one neighboring base
      precedes complete disruption of the H-bonds, followed by unstacking from the
      second neighboring base. Kinetic barriers to melting and hybridization show that
      the central bases melt rapidly near hydrophobic surfaces, which can accelerate
      conformational searching and thereby accelerate folding into the desired
      conformation. 

PMID- 25961883
TI  - Comparison of Long-Term Outcomes between Peritoneal Dialysis Patients with
      Diabetes as a Primary Renal Disease or as a Comorbid Condition.
AB  - OBJECTIVE: To investigate the long-term outcomes of peritoneal dialysis (PD)
      patients with diabetes as primary renal disease and patients with diabetes as a
      comorbid condition. METHODS: All diabetic patients who commenced PD between
      January 1, 1995 and June 30, 2012 at Ren Ji Hospital, China were included.
      Patients were divided into diabetic nephropathy group (DN group) and non-diabetic
      nephropathy group (NDN group) according to their diagnosis of primary renal
      disease at the initiation of PD. They were followed until death, cessation of PD,
      transferred to other centers or to the end of study (June 30, 2013). Outcomes
      were analyzed by Kaplan-Meier method and Cox regression models. RESULTS: A total
      of 163 diabetic patients were enrolled in the study, including 121 (74.2%) in DN
      group and 42 (25.8%) in NDN group. The 1-, 2-, 3- and 5-year patient survival
      rates were 89%, 78%, 66% and 51% for DN group, and 85%, 63%, 53% and 25% for NDN
      group, respectively. Kaplan-Meier analysis showed that patients in NDN group had
      a worse patient survival compared with DN group (log rank 4.830, P=0.028).
      Patients in NDN group had a marginally shorter peritonitis-free period (log rank
      3.297, P=0.069), however, there was no significant difference in technique
      survival (log rank 0.040, P=0.841). Multivariate Cox regression analysis showed
      that older age (HR 1.047, 95% CI 1.022-1.073, p<0.001), cardiovascular disease
      comorbidity (HR 2.200, 95% CI 0.1.269-3.814, P=0.005) and diabetes as a
      comorbidity condition (HR 1.806, 95% CI 1.003-3.158, P=0.038) were the
      independent predictors of increased mortality. CONCLUSIONS: PD patients with
      diabetes as a comorbidity had an inferior patient survival compared to those with
      diabetic nephropathy, and closer monitoring and extra attention in the former
      subgroup of patients are therefore warranted.

PMID- 25961884
TI  - The Next Generation of Dietitians: Implementing Dietetics Education and Practice
      in Integrative Medicine.
AB  - Integrative medicine is a quickly expanding field of health care that emphasizes
      nutrition as a key component. Dietitians and nutritionists have an opportunity to
      meet workforce demands by practicing dietetics and integrative medicine (DIM).
      The purpose of this article is to describe a DIM education program and practicum.
      We report the results of an interprofessional nutrition education and practicum
      program between the University of Kansas Medical Center (KUMC) Department of
      Dietetics and Nutrition and KU Integrative Medicine. This partnered program
      provides training that builds on the strong foundation of the Nutrition Care
      Process and adds graduate-level educational and practicum experiences in
      foundational integrative medicine knowledge, including nutritional approaches
      from a systems biology perspective, nutrigenomics, and biochemistry as the core
      knowledge to understand the root cause of a chronic disorder and to choose
      appropriate nutritional tools for interventions. This interprofessional KUMC
      program provides a dietetic internship, master's degree, and graduate certificate
      in DIM and fulfills a need for dietitians and nutritionists who seek careers
      practicing in an integrative medicine setting. The program fulfills expanding
      workforce needs to provide quality health care for patients with chronic
      illnesses. 

PMID- 25961886
TI  - Parallel nanomanufacturing via electrohydrodynamic jetting from microfabricated
      externally-fed emitter arrays.
AB  - We report the design, fabrication, and characterization of planar arrays of
      externally-fed silicon electrospinning emitters for high-throughput generation of
      polymer nanofibers. Arrays with as many as 225 emitters and with emitter density
      as large as 100 emitters cm(-2) were characterized using a solution of dissolved
      PEO in water and ethanol. Devices with emitter density as high as 25 emitters cm(
      2) deposit uniform imprints comprising fibers with diameters on the order of a
      few hundred nanometers. Mass flux rates as high as 417 g hr(-1) m(-2) were
      measured, i.e., four times the reported production rate of the leading commercial
      free-surface electrospinning sources. Throughput increases with increasing array
      size at constant emitter density, suggesting the design can be scaled up with no
      loss of productivity. Devices with emitter density equal to 100 emitters cm(-2)
      fail to generate fibers but uniformly generate electrosprayed droplets. For the
      arrays tested, the largest measured mass flux resulted from arrays with larger
      emitter separation operating at larger bias voltages, indicating the strong
      influence of electrical field enhancement on the performance of the devices.
      Incorporation of a ground electrode surrounding the array tips helps equalize the
      emitter field enhancement across the array as well as control the spread of the
      imprints over larger distances. 

PMID- 25961885
TI  - In-vitro suppression of IL-6 and IL-8 release from human pulmonary epithelial
      cells by non-anticoagulant fraction of enoxaparin.
AB  - BACKGROUND: Enoxaparin, a mixture of anticoagulant and non-anticoagulant
      fractions, is widely used as an anticoagulant agent. However, it is also reported
      to possess anti-inflammatory properties. Our study indicated that enoxaparin
      inhibits the release of IL-6 and IL-8 from A549 pulmonary epithelial cells. Their
      release causes extensive lung tissue damage. The use of enoxaparin as an anti
      inflammatory agent is hampered due to the risk of bleeding associated with its
      anticoagulant fractions. Therefore, we aimed to identify the fraction responsible
      for the observed anti-inflammatory effect of enoxaparin and to determine the
      relationship between its structure and biological activities. METHODS: A549
      pulmonary epithelial cells were pre-treated in the presence of enoxaparin and its
      fractions. The levels of IL-6 and IL-8 released from the trypsin-stimulated cells
      were measured by ELISA. The anticoagulant activity of the fraction responsible
      for the effect of enoxaparin was determined using an anti-factor-Xa assay. The
      fraction was structurally characterised using nuclear magnetic resonance. The
      fraction was 2-O, 6-O or N-desulfated to determine the position of sulfate groups
      required for the inhibition of interleukins. High-performance size-exclusion
      chromatography was performed to rule out that the observed effect was due to the
      interaction between the fraction and trypsin or interleukins. RESULTS: Enoxaparin
      (60 MUg/mL) inhibited the release of IL-6 and IL-8 by >30%. The fraction
      responsible for this effect of enoxaparin was found to be a disaccharide composed
      of alpha-L-iduronic-acid and alpha-D-glucosamine-6-sulfate. It (15 MUg/mL)
      inhibited the release of interleukins by >70%. The 6-O sulphate groups were
      responsible for its anti-inflammatory effect. The fraction did not bind to
      trypsin or interleukins, suggesting the effect was not due to an artefact of the
      experimental model. CONCLUSION: The identified disaccharide has no anticoagulant
      activity and therefore eliminates the risk of bleeding associated with
      enoxaparin. Future in-vivo studies should be designed to validate findings of the
      current study.

PMID- 25961887
TI  - Neuroelectronics and Biooptics: Closed-Loop Technologies in Neurological
      Disorders.
AB  - Brain-implanted devices are no longer a futuristic idea. Traditionally, therapies
      for most neurological disorders are adjusted based on changes in clinical
      symptoms and diagnostic measures observed over time. These therapies are commonly
      pharmacological or surgical, requiring continuous or irreversible treatment
      regimens that cannot respond rapidly to fluctuations of symptoms or isolated
      episodes of dysfunction. In contrast, closed-loop systems provide intervention
      only when needed by detecting abnormal neurological signals and modulating them
      with instantaneous feedback. Closed-loop systems have been applied to several
      neurological conditions (most notably epilepsy and movement disorders), but
      widespread use is limited by conceptual and technical challenges. Herein, we
      discuss how advances in experimental closed-loop systems hold promise for
      improved clinical benefit in patients with neurological disorders. 

PMID- 25961888
TI  - Molecular evolution of the Sorghum Maturity Gene Ma3.
AB  - Time to maturity is a critical trait in sorghum (Sorghum bicolor) breeding, as it
      determines whether a variety can be grown in a particular cropping system or
      ecosystem. Understanding the nucleotide variation and the mechanisms of molecular
      evolution of the maturity genes would be helpful for breeding programs. In this
      study, we analyzed the nucleotide diversity of Ma3, an important maturity gene in
      sorghum, using 252 cultivated and wild sorghum materials from all over the world.
      The nucleotide variation and diversity were analyzed based both on race- and
      usage-based groups. We also sequenced 12 genes around the Ma3 gene in 185 of
      these materials to search for a selective sweep and found that purifying
      selection was the strongest force on Ma3, as low nucleotide diversity and low
      frequency amino acid variants were observed. However, a very special mutation,
      described as ma3R, seemed to be under positive selection, as indicated by
      dramatically reduced nucleotide variation not only at the loci but also in the
      surrounding regions among individuals carrying the mutations. In addition, in an
      association study using the Ma3 nucleotide variations, we detected 3 significant
      SNPs for the heading date at a high-latitude environment (Beijing) and 17 at a
      low-latitude environment (Hainan). The results of this study increases our
      understanding of the evolutionary mechanisms of the maturity genes in sorghum and
      will be useful in sorghum breeding. 

PMID- 25961890
TI  - Household Food Insecurity is Associated with Respiratory Infections Among 6-11
      Month Old Infants in Rural Ghana.
AB  - BACKGROUND: To determine the relationship between household food insecurity
      (HHFI) and symptoms of respiratory infections among infants in rural Ghana.
      METHODS: The study was cross-sectional. The outcome variables were symptoms of
      respiratory infections (cough and nasal discharge) in infants. HHFI was measured
      using a 15-item modified U.S. Department of Agriculture (USDA) household food
      security module. Households were classified as food insecure if they had an
      affirmative answer for at least 1 item. Associations were examined using multiple
      logistic regression analysis. Data were collected in 32 communities located in 3
      rural subdistricts in the Upper Manya Krobo district of the Eastern region of
      Ghana. The sample included 367 infants aged 6-11 months who attended a community
      based growth monitoring session. RESULTS: Overall, 20.5% of households reported
      experiencing food insecurity in the last month. Compared with infants in food
      secure households, infants living in food insecure households were about twice as
      likely to experience cough (adjusted odds ratio: 2.25, 95% confidence intervals:
      1.25, 4.04) and nasal discharge (adjusted odds ratio: 1.87, 95% confidence
      intervals: 1.05, 3.36). CONCLUSION: Infants living in food insecure households
      are at an increased risk of respiratory tract morbidity. Interventions that
      address HHFI might be important to improve infant health in rural Ghana.

PMID- 25961891
TI  - Factors Affecting Staphylococcus aureus Colonization of the Nasopharynx in the
      First 6 Months of Life.
AB  - BACKGROUND: Staphylococcal aureus (SA) colonization in early infancy is common,
      but the pattern and factors affecting its acquisition and persistence in the
      first few months of life are not well studied. The aim is to study the rate of SA
      nasopharyngeal (NP) colonization at monthly intervals in the first 6 months of
      life and its association with environmental and host factors and other pathogenic
      NP bacteria. METHODS: Data from a prospective study were analyzed on bacterial
      cultures of 1765 NP swabs from 367 infants who were followed from birth to 6
      months of age. Demographic, breastfeeding, cigarette smoke exposure and day care
      attendance data were collected at each monthly visit. RESULTS: The rate of
      infants colonized with SA was highest at age 1 month (25%) and declined to lowest
      rate by age 6 months (12%). The proportion of SA strains that was methicillin
      resistant SA was also highest at age 1 month and declined rapidly by age 4 months
      (18% vs. 6%, P = 0.05). Colonization with Streptococcus pneumoniae (SP),
      nontypeable Haemophilus influenzae (NTHI) and Moraxella catarrhalis (MC)
      increased at different rates up to age 6 months. Univariate analysis showed that
      SA colonization rate was significantly lower with increasing age, black race, day
      care attendance, and colonization with NTHI, MC and SP (P < 0.05). Multivariate
      analysis showed that this effect was independently associated only with
      increasing age and MC colonization (P < 0.05). Furthermore, the time to first
      acquisition of SA from one month of age onwards was significantly associated with
      day care attendance, and NTHI and MC colonization. None of the infants colonized
      with SA developed SA infections through age 6 months. CONCLUSIONS: SA
      colonization of NP begins very early in life and declines quickly. Methicillin
      resistant SA has lower ability to maintain prolonged colonization status than
      methicillin-susceptible strains in the first 6 months of life. As the NP is
      colonized with other respiratory bacterial pathogens, the colonization with SA
      declines; however, this effect is stronger with Gram-negative bacteria, such as
      NTHI and MC.

PMID- 25961889
TI  - Meconium Tenofovir Concentrations and Growth and Bone Outcomes in Prenatally
      Tenofovir Exposed HIV-Uninfected Children.
AB  - BACKGROUND: Maternal tenofovir disoproxil fumarate (TDF) treatment among HIV
      infected pregnant women results in fetal tenofovir (TFV) exposure. Fetal TFV
      toxicity was demonstrated in animals, but most clinical investigations have not
      observed toxicity in humans. METHODS: We evaluated HIV-exposed, uninfected
      infants in the Surveillance Monitoring for Antiretroviral Therapy Toxicities
      cohort of the Pediatric HIV/AIDS Cohort Study whose mothers were prescribed TDF
      for >= 8 third trimester weeks. Infant dual-energy X-ray absorptiometry scans
      were obtained at 0-4 weeks to measure whole body bone mineral content. Meconium
      TFV concentrations were quantified by liquid chromatography-tandem mass
      spectrometry. RESULTS: Fifty-eight TFV-exposed infants had meconium TFV
      quantified. Detectable concentrations were 11-48,100 ng/g; 3 infants had
      undetectable concentrations. Maternal TDF prescription duration ranged from 8 to
      41 gestational weeks; infant gestational ages were 36-41 weeks. Meconium TFV
      concentrations were not correlated with TFV exposure duration or timing and did
      not vary by concomitant prescription of protease inhibitors. Increased meconium
      TFV concentrations were associated with greater gestational ages (rho = 0.29, P =
      0.03) and lower maternal plasma HIV RNA before delivery (rho = -0.29, P = 0.04).
      Meconium TFV concentrations were not associated with infant weight, length (n =
      58) or bone mineral content (n = 49). CONCLUSIONS: For the first time, we
      explored associations between meconium TFV concentrations and infant growth and
      bone measurements; we did not observe a meconium concentration-dependent
      relationship for these infant outcomes. These findings support other clinical
      research failing to show dose-response relationships for growth and bone outcomes
      among intrauterine TFV-exposed infants. High meconium TFV concentrations
      correlated with low maternal viral load, suggesting maternal TDF adherence
      significantly contributes to meconium TFV concentrations.

PMID- 25961892
TI  - Fever and Reversible Laboratory Abnormalities Associated with Prolonged Use of
      Piperacillin-Tazobactam in Children.
AB  - Piperacillin-tazobactam is used frequently in pediatric patients with complicated
      appendicitis and other intra-abdominal infections. We report 10 pediatric
      patients who developed a piperacillin-tazobactam-associated adverse reaction
      characterized by fever, rash, hematologic abnormalities and transaminitis.
      Physicians should be aware of this entity in patients treated with a prolonged
      course of piperacillin-tazobactam. Prompt identification can obviate unnecessary
      diagnostic testing and treatment. 

PMID- 25961893
TI  - Association of White Blood Cell Count and C-Reactive Protein with Outcomes in
      Children Hospitalized for Community-acquired Pneumonia.
AB  - We examined the association between baseline peripheral white blood cell count
      and C-reactive protein (CRP) values with outcomes among 153 children hospitalized
      with pneumonia. In multivariable analyses, CRP, but not white blood cell count,
      was significantly associated with both fever duration and hospital length of
      stay. For every 1mg/dL increase in CRP, length of stay increased by 1 hour. 

PMID- 25961894
TI  - Population-based Incidence and Etiology of Community-acquired Neonatal Viral
      Infections in Bangladesh: A Community-based and Hospital-based Surveillance
      Study.
AB  - BACKGROUND: The etiology of >90% of cases of suspected neonatal infection remains
      unknown. We conducted community-based surveillance in conjunction with hospital
      based surveillance in a rural region in Bangladesh from June 2006 to September
      2007 to assess the incidence and etiology of community-acquired viral infections
      among neonates. METHODS: Community health workers (CHWs) assessed neonates at
      home on days 0, 2, 5 and 8 after birth and referred cases of suspected illness to
      the hospital (CHW surveillance). Among neonates with clinically suspected upper
      respiratory tract infection (URTI), pneumonia, sepsis and/or meningitis, virus
      identification studies were conducted on nasal wash, cerebrospinal fluid and/or
      blood specimens. In the hospital-based surveillance, similar screening was
      conducted among all neonates (referred by CHWs and self-referred) who were
      admitted to the hospital. RESULTS: CHW surveillance found an incidence rate of
      15.6 neonatal viral infections per 1000 live births with 30% of infections
      identified on the day of birth. Among neonates with suspected sepsis, a viral
      etiology was identified in 36% of cases, with enterovirus accounting for two
      thirds of those infections. Respiratory syncytial virus was the most common
      etiologic agent among those with viral pneumonia (91%) and URTI (68%). There was
      a low incidence (1.2%) of influenza in this rural population. CONCLUSION: Viral
      infections are commonly associated with acute newborn illness, even in the early
      neonatal period. The estimated incidence was 5-fold greater than reported
      previously for bacterial infections. Low-cost preventive measures for neonatal
      viral infections are urgently needed.

PMID- 25961895
TI  - Group A Streptococcal Carriage and Seroepidemiology in Children up to 10 Years of
      Age in Australia.
AB  - BACKGROUND: Group A streptococci (GAS) and other beta-hemolytic streptococci
      (BHS) cause pharyngitis, severe invasive disease and serious nonsuppurative
      sequelae including rheumatic heart disease and post streptococcal
      glomerulonephritis. The aim of this study was to assess carriage rates and anti
      streptococcal C5a peptidase (anti-SCP) IgG levels and identify epidemiologic
      factors related to carriage or seropositivity in Australian children. METHODS: A
      throat swab and blood sample were collected for microbiological and serological
      analysis (anti-SCP IgG) in 542 healthy children aged 0-10 years. Sequence
      analysis of the SCP gene was performed. Serological analysis used a competitive
      Luminex Immunoassay designed to preferentially detect functional antibody.
      RESULTS: GAS-positive culture prevalence in throat swabs was 5.0% (range 0-10%),
      with the highest rate in 5 and 9 years old children. The rate of non-GAS BHS
      carriage was low (<1%). The scp gene was present in all 22 isolates evaluated. As
      age of child increased, the rate of carriage increased; odds ratio, 1.14 (1.00,
      1.29); P = 0.50. Geometric mean anti-SCP titers increased with each age-band from
      2 to 7 years, then plateaued. Age, geographic location and number of children
      within the household were significantly associated with the presence of anti-SCP
      antibodies. CONCLUSIONS: Children are exposed to GAS and other BHS at a young
      age, which is important for determining the target age for vaccination to protect
      before the period of risk.

PMID- 25961896
TI  - Australia-wide Point Prevalence Survey of Antimicrobial Prescribing in Neonatal
      Units: How Much and How Good?
AB  - BACKGROUND: There is increasing recognition of the threat to neonatal patients
      from antibiotic resistance. There are limited data on antimicrobial prescribing
      practices for hospitalized neonates. We aimed to describe antimicrobial use in
      hospitalized Australian neonatal patients, and to determine its appropriateness.
      METHODS: Multicentre single-day hospital-wide point prevalence survey in 2012, in
      conjunction with the Antimicrobial Resistance and Prescribing in European
      Children study. The appropriateness of antimicrobial prescriptions was also
      assessed. All patients admitted at 8 am on the survey day, in 6 neonatal units in
      tertiary children's hospitals across 5 states, were included in an analysis of
      the quantity and quality of all antimicrobial prescriptions. RESULTS: The point
      prevalence survey included 6 neonatal units and 236 patients. Of 109 patients
      (46%) receiving at least 1 antimicrobial, 66 (61%) were being treated for
      infection, with sepsis the most common indication. There were 216 antimicrobial
      prescriptions, 134 (62%) for treatment of infection and 82 (38%) for prophylaxis,
      mostly oral nystatin. Only 15 prescriptions were for targeted as opposed to
      empirical treatment. Penicillin and gentamicin were the most commonly prescribed
      antibiotics, with vancomycin third most common. Half of all treated patients were
      receiving combination antimicrobial therapy. There was marked variation in
      vancomycin and gentamicin dosing. Overall, few prescriptions (4%) were deemed
      inappropriate. CONCLUSION: This is the first Australia-wide point prevalence
      survey of neonatal antimicrobial prescribing in tertiary children's hospitals.
      The findings highlight positive practices and potential targets for quality
      improvement.

PMID- 25961898
TI  - Ensuring sustainability of non-networked sanitation technologies: an approach to
      standardization.
AB  - Non-networked sanitation technologies use no sewer, water or electricity lines.
      Based on a review of 45 commercially distributed technologies, 12 (representing
      three concepts) were selected for a detailed audit. They were located in six
      countries of Africa and Asia. The safety of users was generally assured and the
      costs per use were not excessive, whereas costs were fully transparent for only
      one technology surveyed. A main drawback was insufficient quality of the
      byproducts from on-site treatment, making recycling in agriculture a hygienic and
      environmental risk. Further, no technology was sufficiently mature (requiring
      e.g. to shift wastes by hand). In order to promote further development and give
      producers of mature products a competitive advantage, the paper proposes a
      certification of technologies to confirm the fulfillment of basic requirements to
      make them attractive for future users. 

PMID- 25961899
TI  - Comment on "Isomer Specific Product Detection in the Reaction of CH with
      Acrolein".

PMID- 25961900
TI  - Weight, Weight Perceptions, and Health-Related Quality of Life Among a National
      Sample of US Girls.
AB  - OBJECTIVE: To examine associations between 3 weight indices (weight status,
      perceived weight, and weight status perception accuracy) and heath-related
      quality of life (HRQOL). METHODS: Data are for girls in the 2009 Health Behaviors
      in School-Age Children survey, a nationally representative sample of students in
      Grades 5 to 10 during the 2009/2010 school year (n = 5018). Controlling for
      sociodemographics, multivariate linear regressions examined associations between
      self-reported weight status (underweight/normal/overweight/obese), perceived
      weight (how children categorize their weight), weight status perception accuracy
      (underestimate/accurate perception/overestimate), and dimensions of HRQOL,
      including physical, emotional, social, and school functioning. RESULTS: Although
      obesity was only associated with poor physical and emotional HRQOL, perceptions
      of being overweight were associated with worse physical, emotional, school, and
      social HRQOL. Furthermore, girls who overestimated their weight reported poorer
      HRQOL than those with accurate weight perceptions. Associations of perceptions of
      being overweight and weight status overestimation with poor HRQOL despite, in
      most instances, the absence of associations between weight status and HRQOL
      suggest that weight status perceptions may not merely be a mediator of a weight
      status-HRQOL association but a significant independent correlate of poor HRQOL.
      CONCLUSION: These findings raise the issue of whether there is a need to
      prioritize intervention efforts to promote better HRQOL by redefining the
      population of girls most at risk. Parents, teachers, and clinicians should be
      aware that, rather than overweight status, perceptions of being overweight
      (accurately or not) are associated with a poor HRQOL among girls. Future research
      should examine the potential negative effect of using specific body image
      terminologies on adolescents' psychological health.

PMID- 25961901
TI  - Subjective health, school victimization, and protective factors in a high-risk
      school sample.
AB  - OBJECTIVE: School victimization has adverse effects on mental and physical
      health. However, little is known about the influence of protective factors,
      socioeconomic status (SES), or a migration background (MB) on this association.
      The authors analyzed data from a multicenter longitudinal school study with a
      high proportion of pupils with a low SES and an MB. Victimization was defined as
      bullying or the experiences of interpersonal violence. METHODS: In a cross
      sectional design, 2483 pupils of secondary schools in northern Germany completed
      standardized questionnaires measuring families' SES, MB, school victimization,
      psychosomatic complaints, life satisfaction, health-related quality of life
      (HRQoL), and social and personal protective factors. The authors tested the
      association between victimization, low protective factors, low SES and MB, and
      subjective health parameters using linear regression models. RESULTS: A total of
      39% of the pupils reported being bullied, and 16% had experienced interpersonal
      violence. Victimized children reported twice as many psychosomatic problems,
      lower life satisfaction, and reduced HRQoL (p < .001) compared with children
      without victimization experiences. Regression models confirmed this association;
      in addition to victimization, low social and especially low personal protective
      factors increased the risk for low subjective health parameters. The SES and MB
      had no influence on the outcomes. CONCLUSION: The results underscore the strong
      association between school victimization and low subjective health factors.
      Strengthening pupils' self-efficacy and a supportive school climate can diminish
      the health consequences of victimization.

PMID- 25961902
TI  - Family impact of acquired brain injury in children and youth.
AB  - OBJECTIVE: To assess the parental view on the impact of pediatric traumatic brain
      injury (TBI) and nontraumatic brain injury (NTBI) on the family and its
      determinants. METHODS: Follow-up study including parents of children with a
      hospital-based diagnosis of acquired brain injury (ABI) aged 4-20 years at onset
      of ABI. Parents completed the Pediatric Quality of Life Inventory Family Impact
      Module (PedsQL FIM), which measures Parent Health-Related Quality of Life, Family
      Functioning, Communication, and Worry. Additional assessments included the
      Pediatric Stroke Outcome Measure (PSOM), the Child & Family Follow-up Survey
      (CFFS), PedsQL General Core and Multiple Fatigue Scales, and sociodemographic and
      disease characteristics. RESULTS: Parents of 108 patients, median age 13 years
      (range 5-22), completed the questionnaires 24-30 months after diagnosis. There
      were 81 patients with TBI of whom 11 (14%) with moderate/severe TBI and 27
      patients with NTBI of whom 5 (19%) with moderate/severe NTBI. The median PedsQL
      FIM Total Scale was 80.4 (SD 16.1). The PedsQL FIM Total Scale and 4 out of 5
      Subscale Scores were statistically significantly better in the TBI group than in
      the NTBI group and in patients with severe NTBI than with mild/moderate NTBI.
      Moreover, in the total group, there were significant univariate associations
      between the FIM Total Scale and/or one or more Subscale Scores and age, preinjury
      patient health problems, and the PSOM, CFFS, PedsQL General Core, and Multiple
      Fatigue Scales. In the multivariable analysis, the FIM Total Scale was
      significantly associated with type and severity of injury and preinjury patient
      health problems. CONCLUSIONS: Two years after onset, the parent-reported that
      impact of ABI on the family as measured by the PedsQL FIM was considerable
      especially in patients with moderate/severe NTBI.

PMID- 25961903
TI  - A model for the development of mothers' perceived vulnerability of preterm
      infants.
AB  - OBJECTIVE: Some mothers of preterm infants continue to view them as vulnerable
      after their health has improved. These exaggerated perceptions of vulnerability
      lead to poor parent-child interactions and, subsequently, to adverse child
      outcomes. However, there is no theoretical model to explain why these exaggerated
      perceptions develop in only some mother-child dyads. METHOD: Data for this study
      come from a randomized trial of an intervention to reduce distress in mothers of
      preterm infants. A total of 105 mothers older than 18 years of infants aged 25-34
      weeks, weighing >600 g and with clinically significant anxiety, depression, or
      trauma symptoms, were recruited and randomized. Women were assessed at baseline,
      after intervention, and at 6 months after birth. The outcome for these analyses
      was perceptions of infant vulnerability as measured by the Vulnerable Baby Scale
      (VBS) at 6 months after birth. A theoretical model developed from the extant
      literature was tested using the MacArthur Mediator-Moderator Approach. RESULTS: A
      dysfunctional coping style, high depression, anxiety, or trauma symptoms in
      response to the preterm birth, and low social support were related to 6-month VBS
      scores. Maternal response to trauma was directly related to VBS, and an important
      precursor of maternal response to trauma was a dysfunctional coping style.
      CONCLUSIONS: This model suggests that maternal responses to trauma are critical
      in the formation of exaggerated perceptions of vulnerability as are dysfunctional
      coping styles and low social support. Women with these characteristics should be
      targeted for intervention to prevent poor parenting practices that result from
      exaggerated perceptions of vulnerability.

PMID- 25961904
TI  - Behavioral changes associated with a disruptive new student in the classroom.
AB  - CASE: Marcus is a 10-year-old boy who was followed by his pediatrician for
      several years. She knows him as a socially engaged, active athlete, playing
      soccer and baseball, out-going, and a good student. He has been in good health
      without a significant medical history.At the beginning of this academic year, a
      new student was placed in Marcus's fourth grade class. This student is
      disruptive, impulsive, and abusive. He has frequent violent outbursts, yelling,
      kicking, and throwing objects, including recently throwing a desk across the
      room. The school has made efforts to manage this student. The teacher sets up
      behavior contracts, and the school has temporarily suspended the child; however,
      the school is unable to remove the child from the classroom. Many students,
      including Marcus, have been significantly affected by this disruption.Marcus
      describes the classroom environment as "tense." He reports he is never sure what
      is going to make the student "so mad." Over the last 3-4 months, Marcus developed
      nightmares, enuresis, and trichotillomania. The hair pulling is the most
      distressing feature for both Marcus and his parents. Marcus acknowledges that he
      is usually unaware of the behavior at first but then finds the sensation is
      relaxing. Afterward, he is typically embarrassed by the behavior. There is a
      family history of anxiety in both parents.He has been seeing a psychologist with
      some mild improvement in his enuresis. However, the hair pulling has not improved
      and has worsened. They were seeking additional advice regarding the next steps.

PMID- 25961906
TI  - Mannich Bases as Enone Precursors for Water-Mediated Efficient Synthesis of 2,3,6
      Trisubstituted Pyridines and 5,6,7,8-Tetrahydroquinolines.
AB  - A highly efficient, regioselective, and environmentally friendly method has been
      developed for water-mediated synthesis of 2,3,6-trisubstituted pyridines and
      5,6,7,8-tetrahydroquinolines. The introduced method allows easy preparation of
      various polysubstituted pyridines and 5,6,7,8-tetrahydroquinolines via domino
      reaction of an enolizable ketone, ammonia and enones derived from different
      Mannich bases in mild reaction conditions. Montmorillonite K-10 promoted this one
      pot three-component reaction and gave both new and known 2,3,6-trisubstituted
      pyridines and 5,6,7,8-tetrahydroquinolines in good yields. The reaction protocol
      provides a wide array of functionality in construction of polysubstituted
      pyridines and 5,6,7,8-tetrahydroquinolines from commercially available starting
      materials in easily applicable and environmentally friendly conditions. 

PMID- 25961905
TI  - Extensive decoupling of metabolic genes in cancer.
AB  - Tumorigenesis requires the re-organization of metabolism to support malignant
      proliferation. We examine how the altered metabolism of cancer cells is reflected
      in the rewiring of co-expression patterns among metabolic genes. Focusing on
      breast and clear-cell kidney tumors, we report the existence of key metabolic
      genes which act as hubs of differential co-expression, showing significantly
      different co-regulation patterns between normal and tumor states. We compare our
      findings to those from classical differential expression analysis, and
      counterintuitively observe that the extent of a gene's differential co-expression
      only weakly correlates with its differential expression, suggesting that the two
      measures probe different features of metabolism. Focusing on this discrepancy, we
      use changes in co-expression patterns to highlight the apparent loss of
      regulation by the transcription factor HNF4A in clear cell renal cell carcinoma,
      despite no differential expression of HNF4A. Finally, we aggregate the results of
      differential co-expression analysis into a Pan-Cancer analysis across seven
      distinct cancer types to identify pairs of metabolic genes which may be
      recurrently dysregulated. Among our results is a cluster of four genes, all
      components of the mitochondrial electron transport chain, which show significant
      loss of co-expression in tumor tissue, pointing to potential mitochondrial
      dysfunction in these tumor types. 

PMID- 25961907
TI  - Controlling the Sensing Properties of Silicon Nanowires via the Bonds Nearest to
      the Silicon Nanowire Surface.
AB  - Controlling the sensing properties of a silicon nanowire field effect transistor
      is dependent on the surface chemistry of the silicon nanowire. A standard silicon
      nanowire has a passive oxide layer (native oxide), which has trap states that
      cause sensing inaccuracies and desensitize the surface to nonpolar molecules. In
      this paper, we successfully modified the silicon nanowire surface with different
      nonoxide C3 alkyl groups, specifically, propyl (Si-CH2-CH2-CH3), propenyl (Si
      CH?CH-CH3), and propynyl (Si-C=C-CH3) modifications. The effect of the near
      surface bond on the sensor sensitivity and stability was explored by comparing
      three C3 surface modifications. A reduction of trap-states led to greater sensor
      stability and accuracy. The propenyl-modified sensor was consistently the most
      stable and sensitive sensor, among the applied sensors. The propenyl- and
      propynyl-modified sensors consistently performed with the best accuracy in
      identifying specific analytes with similar polarity or similar molecular weights.
      A combination of features from different sensing surfaces led to the best rubric
      for specific analytes identification. These results indicate that nonoxide sensor
      surfaces are useful in identifying specific analytes and that a combination of
      sensors with different surfaces in a cross-reactive array can lead to specific
      analytes detection. 

PMID- 25961908
TI  - Atomic Force Microscopy and Voltammetric Investigation of Quadruplex Formation
      between a Triazole-Acridine Conjugate and Guanine-Containing Repeat DNA
      Sequences.
AB  - The interactions of the Tetrahymena telomeric repeat sequence d(TG4T) and the
      polyguanylic acid (poly(G)) sequence with the quadruplex-targeting triazole
      linked acridine ligand GL15 were investigated using atomic force microscopy (AFM)
      at a highly oriented pyrolytic graphite and voltammetry at a glassy carbon
      electrode. GL15 interacted with both sequences, in a time dependent manner, and G
      quadruplex formation was detected. AFM showed the adsorption of quadruplexes as
      small d(TG4T) and poly(G) spherical aggregates and large quadruplex-based poly(G)
      assemblies, and voltammetry showed the decrease and disappearance of GL15 and
      guanine oxidation peak currents and appearance of the G-quadruplex oxidation
      peak. The GL15 molecule strongly stabilized and accelerated G-quadruplex
      formation in both Na(+) and K(+) ion-containing solution, although only K(+)
      promoted the formation of perfectly aligned tetra-molecular G-quadruplexes. The
      small-molecule complex with the d(TG4T) quadruplex is discrete and approximately
      globular, whereas the G-quadruplex complex with poly(G) is formed at a number of
      points along the length of the polynucleotide, analogous to beads on a string. 

PMID- 25961909
TI  - Distinct Impact of Two Keratin Mutations Causing Epidermolysis Bullosa Simplex on
      Keratinocyte Adhesion and Stiffness.
AB  - Keratin filaments constitute the major component of the epidermal cytoskeleton
      from heterodimers of type I and type II keratin subunits. Missense mutations in
      keratin 5 or keratin 14, highly expressed in the basal epidermis, cause the
      severe skin blistering disease epidermolysis bullosa simplex (EBS) in humans by
      rendering the keratin cytoskeleton sensitive to mechanical stress; yet, the
      mechanisms by which individual mutations cause cell fragility are incompletely
      understood. Here, we compared the K14p.Arg125Pro with the K5p.Glu477Asp mutation,
      both giving rise to severe generalized EBS, by stable expression in keratin-free
      keratinocytes. This revealed distinctly different effects on keratin cytoskeletal
      organization, in agreement with in vivo observations, thus validating the cell
      system. Although the K14p.Arg125Pro mutation led to impaired desmosomes,
      downregulation of desmosomal proteins, and weakened epithelial sheet integrity
      upon shear stress, the K5p.Glu477Asp mutation did not impair these functions,
      although causing EBS with squamous cell carcinoma in vivo. Atomic force
      microscopy demonstrated that K14 mutant cells were even less resistant against
      deformation compared with keratin-free keratinocytes. Thus, a keratin mutation
      causing EBS compromises cell stiffness to a greater extent than the lack of
      keratins. Finally, re-expression of K14 in K14 mutant cells did not rescue the
      above defects. Collectively, our findings have implications for EBS therapy
      approaches. 

PMID- 25961910
TI  - Resources Utilization and Costs the Year Before and After Starting Treatment with
      Adalimumab in Crohn's Disease Patients.
AB  - BACKGROUND: This study examines the resources utilization in patients with
      Crohn's disease (CD) during the year before (Y - 1) and after (Y + 1) starting
      treatment with adalimumab and the drug's efficiency. METHODS: Observational,
      multicenter, prospective cohort study of patients with CD naive to biological
      drugs. The proportion of patients with CD Activity Index (CDAI) <150 was
      considered as the effectiveness variable. Costs considered were direct costs (DC)
      related to the use of health care resources, and indirect costs (IC) related to
      sick leave in Y - 1 and Y + 1. Adalimumab efficiency was estimated as the
      incremental cost/effectiveness ratio. A deterministic sensitivity analysis was
      performed building 3 scenarios: base case, the least favorable, and the most
      favorable case for adalimumab. RESULTS: In the cohort of 126 patients (50.8% men;
      age 39.1 +/- 13.8 yr), the proportion of patients in remission increased from
      34.1% by the end of Y - 1 to 83.3% by the end of Y + 1. Although the DC increase
      by the use of adalimumab, the use of doctor visits, emergency room visits,
      laboratory tests, diagnostic examinations, and nonbiological drug treatment were
      lower (P < 0.05) in Y + 1 than Y - 1. In the base case scenario, considering only
      DC, the incremental cost/effectiveness ratio was ?31,308 and including IC, it was
      ?28,936. In patients with CDAI > 150 at the onset, incremental cost/effectiveness
      ratio was ?20,119 and ?18,223, considering DC alone or included IC, respectively.
      CONCLUSIONS: In patients with CD, adalimumab increases pharmacological costs at
      the expense of biological therapy but reduces the cost of other drugs, the use of
      health care resources, and IC. Adalimumab efficiency is 30% greater in patients
      with CDAI > 150.

PMID- 25961911
TI  - Tissue spray ionization mass spectrometry for rapid recognition of human lung
      squamous cell carcinoma.
AB  - Tissue spray ionization mass spectrometry (TSI-MS) directly on small tissue
      samples has been shown to provide highly specific molecular information. In this
      study, we apply this method to the analysis of 38 pairs of human lung squamous
      cell carcinoma tissue (cancer) and adjacent normal lung tissue (normal). The main
      components of pulmonary surfactants, dipalmitoyl phosphatidylcholine (DPPC, m/z
      757.47), phosphatidylcholine (POPC, m/z 782.52), oleoyl phosphatidylcholine
      (DOPC, m/z 808.49), and arachidonic acid stearoyl phosphatidylcholine (SAPC, m/z
      832.43), were identified using high-resolution tandem mass spectrometry. Monte
      Carlo sampling partial least squares linear discriminant analysis (PLS-LDA) was
      used to distinguish full-mass-range mass spectra of cancer samples from the mass
      spectra of normal tissues. With 5 principal components and 30-40 Monte Carlo
      samplings, the accuracy of cancer identification in matched tissue samples
      reached 94.42%. Classification of a tissue sample required less than 1 min, which
      is much faster than the analysis of frozen sections. The rapid, in situ diagnosis
      with minimal sample consumption provided by TSI-MS is advantageous for surgeons.
      TSI-MS allows them to make more informed decisions during surgery.

PMID- 25961912
TI  - PC4 promotes genome stability and DNA repair through binding of ssDNA at DNA
      damage sites.
AB  - The transcriptional cofactor PC4 is an ancient single-strand DNA (ssDNA)-binding
      protein that has a homologue in bacteriophage T5 where it is likely the elusive
      replicative ssDNA-binding protein. We hypothesize that human PC4 has retained
      functions in ssDNA binding to stabilize replication forks and prevent genome
      instability in mammalian cells. Here we demonstrate that PC4 is recruited to
      hydroxyurea (HU)-stalled replication forks, which is dependent on active
      transcription and its ssDNA-binding ability. Interestingly, we demonstrate that
      ssDNA binding by PC4 is critical to suppress spontaneous DNA damage and promote
      cellular survival. PC4 accumulation co-localizes with replication protein A (RPA)
      at stalled forks and is increased upon RPA depletion, demonstrating compensatory
      functions in ssDNA binding. Depletion of PC4 not only results in defective
      resolution of HU-induced DNA damage but also significantly reduces homologous
      recombination repair efficiency. Altogether, our results indicate that PC4 has
      similar functions to RPA in binding ssDNA to promote genome stability, especially
      at sites of replication-transcription collisions. 

PMID- 25961913
TI  - Brg-1 targeting of novel miR550a-5p/RNF43/Wnt signaling axis regulates colorectal
      cancer metastasis.
AB  - Metastasis is one of the main causes of death in patients with colorectal cancer
      (CRC). Brg-1 is a central component of the SWItch/Sucrose NonFermentable
      chromatin-remodeling complex, which features a bromodomain and helicase/ATPase
      activity. The gene encoding Brg-1 is frequently mutated or silenced in human
      cancers. Several reports have proposed Brg-1 as a tumor suppressor; however,
      little is known about its role in oncogenesis and metastasis. Here we
      demonstrated that decreased Brg-1 regulates a novel miR-550a-5p/RNF43/Wnt/beta
      catenin signaling pathway, to promote CRC metastasis in vitro and in vivo. In
      particular, we used high-throughput RNA-sequencing analysis to show that Brg-1
      negatively regulates miR-550a-5p in CRC cells. We further found that Brg-1
      inhibits the transcriptional activity of miR-550a-5p promoter, and that decreased
      Brg-1 expression increased miR-550a-5p expression. We also identified ring finger
      43 (RNF43), an inhibitor of Wnt/beta-catenin signaling, as a target of miR-550a
      5p. Knockdown of Brg-1 by small interfering RNA led to decreased RNF43
      expression, increased Wnt signaling and increased CRC cell migration and
      invasion. This novel pathway defines a new function for Brg-1 and provides
      potential targets for the treatment of Brg-1 mutant and loss-of-function tumors.

PMID- 25961915
TI  - Anti-HER3 monoclonal antibody patritumab sensitizes refractory non-small cell
      lung cancer to the epidermal growth factor receptor inhibitor erlotinib.
AB  - Human epidermal growth factor receptor (HER) 3 is aberrantly overexpressed and
      correlates with poor prognosis in non-small cell lung cancer (NSCLC). Patritumab
      is a monoclonal antibody against HER3 that has shown promising results in early
      phase clinical trials, but an optimal target population for the drug has yet to
      be identified. In the present study, we examined whether heregulin, a HER3 ligand
      that is also overexpressed in a subset of NSCLC, can be used as a biomarker to
      predict the antitumorigenic efficacy of patritumab and whether the drug can
      overcome the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR
      TKI) resistance induced by heregulin. Patritumab sensitivity was associated with
      heregulin expression, which, when abolished, resulted in the loss of HER3 and AKT
      activation and growth arrest. Furthermore, heregulin overexpression induced EGFR
      TKI resistance in NSCLC cells harbouring an activating EGFR mutation, while HER3
      and AKT activation was maintained in the presence of erlotinib in heregulin
      overexpressing, EGFR-mutant NSCLC cells. Sustained HER3-AKT activation was
      blocked by combining erlotinib with either anti-HER2 or anti-HER3 antibody.
      Notably, heregulin was upregulated in tissue samples from an NSCLC patient who
      had an activating EGFR mutation but was resistant to the TKI gefitinib. These
      results indicate that patritumab can overcome heregulin-dependent EGFR inhibitor
      resistance in NSCLC in vitro and in vivo and suggest that it can be used in
      combination with EGFR TKIs to treat a subset of heregulin-overexpressing NSCLC
      patients. 

PMID- 25961914
TI  - Deficiency in WT1-targeting microRNA-125a leads to myeloid malignancies and
      urogenital abnormalities.
AB  - The Wilms' tumor gene WT1 is overexpressed in leukemia and solid tumors and has
      an oncogenic role in leukemogenesis and tumorigenesis. However, precise
      regulatory mechanisms of WT1 overexpression remain undetermined. In the present
      study, microRNA-125a (miR-125a) was identified as a miRNA that suppressed WT1
      expression via binding to the WT1-3'UTR. MiR-125a knockout mice overexpressed
      WT1, developed myeloproliferative disorder (MPD) characterized by expansion of
      myeloid cells in bone marrow (BM), spleen and peripheral blood, and displayed
      urogenital abnormalities. Silencing of WT1 expression in hematopoietic
      stem/progenitor cells of miR-125a knockout MPD mice by short-hairpin RNA
      inhibited myeloid colony formation in vitro. Furthermore, the incidence and
      severity of MPD were lower in miR-125a (-/-) mice than in miR-125a (+/-) mice,
      indicating the operation of compensatory mechanisms for the complete loss of miR
      125a. To elucidate the compensatory mechanisms, miRNA array was performed. MiR
      486 was occasionally induced in compete loss of miR-125a and inhibited WT1
      expression instead of miR-125a, resulting in the cancellation of MPD occurrence.
      These results showed for the first time the post-transcriptional regulatory
      mechanisms of WT1 by both miR-125a and miR-486 and should contribute to the
      elucidation of mechanisms of normal hematopoiesis and kidney development. 

PMID- 25961916
TI  - Therapeutic potential of targeting IRES-dependent c-myc translation in multiple
      myeloma cells during ER stress.
AB  - Protein translation is inhibited by the unfolded protein response (UPR)-induced
      eIF-2alpha phosphorylation to protect against endoplasmic reticulum (ER) stress.
      In addition, we found additional inhibition of protein translation owing to
      diminished mTORC1 (mammalian target of rapamycin complex1) activity in ER
      stressed multiple myeloma (MM) cells. However, c-myc protein levels and myc
      translation was maintained. To ascertain how c-myc was maintained, we studied myc
      IRES (internal ribosome entry site) function, which does not require mTORC1
      activity. Myc IRES activity was upregulated in MM cells during ER stress induced
      by thapsigargin, tunicamycin or the myeloma therapeutic bortezomib. IRES activity
      was dependent on upstream MAPK (mitogen-activated protein kinase) and MNK1 (MAPK
      interacting serine/threonine kinase 1) signaling. A screen identified hnRNP A1
      (A1) and RPS25 as IRES-binding trans-acting factors required for ER stress
      activated activity. A1 associated with RPS25 during ER stress and this was
      prevented by an MNK inhibitor. In a proof of principle, we identified a compound
      that prevented binding of A1 to the myc IRES and specifically inhibited myc IRES
      activity in MM cells. This compound, when used alone, was not cytotoxic nor did
      it inhibit myc translation or protein expression. However, when combined with ER
      stress inducers, especially bortezomib, a remarkable synergistic cytotoxicity
      ensued with associated inhibition of myc translation and expression. These
      results underscore the potential for targeting A1-mediated myc IRES activity in
      MM cells during ER stress. 

PMID- 25961917
TI  - Rho1-Wnd signaling regulates loss-of-cell polarity-induced cell invasion in
      Drosophila.
AB  - Both cell polarity and c-Jun N-terminal kinase (JNK) activity are essential to
      the maintenance of tissue homeostasis, and disruption of either is commonly seen
      in cancer progression. Despite the established connection between loss-of-cell
      polarity and JNK activation, much less is known about the molecular mechanism by
      which aberrant cell polarity induces JNK-mediated cell migration and tumor
      invasion. Here we show results from a genetic screen using an in vivo invasion
      model via knocking down cell polarity gene in Drosophila wing discs, and identify
      Rho1-Wnd signaling as an important molecular link that mediates loss-of-cell
      polarity-triggered JNK activation and cell invasion. We show that Wallenda (Wnd),
      a protein kinase of the mitogen-activated protein kinase kinase kinase family, by
      forming a complex with the GTPase Rho1, is both necessary and sufficient for Rho1
      induced JNK-dependent cell invasion, MMP1 activation and epithelial-mesenchymal
      transition. Furthermore, Wnd promotes cell proliferation and tissue growth
      through wingless production when apoptosis is inhibited by p35. Finally, Wnd
      shows oncogenic cooperation with Ras(V12) to trigger tumor growth in eye discs
      and causes invasion into the ventral nerve cord. Together, our data not only
      provides a novel mechanistic insight on how cell polarity loss contributes to
      cell invasion, but also highlights the value of the Drosophila model system to
      explore human cancer biology. 

PMID- 25961918
TI  - USP7 is essential for maintaining Rad18 stability and DNA damage tolerance.
AB  - Rad18 functions at the cross-roads of three different DNA damage response (DDR)
      pathways involved in protecting stressed replication forks: homologous
      recombination repair, DNA inter-strand cross-link repair and DNA damage
      tolerance. Although Rad18 serves to facilitate replication of damaged genomes by
      promoting translesion synthesis (TLS), this comes at a cost of potentially error
      prone lesion bypass. In contrast, loss of Rad18-dependent TLS potentiates the
      collapse of stalled forks and leads to incomplete genome replication. Given the
      pivotal nature with which Rad18 governs the fine balance between replication
      fidelity and genome stability, Rad18 levels and activity have a major impact on
      genomic integrity. Here, we identify the de-ubiquitylating enzyme USP7 as a
      critical regulator of Rad18 protein levels. Loss of USP7 destabilizes Rad18 and
      compromises UV-induced PCNA mono-ubiquitylation and Pol eta recruitment to
      stalled replication forks. USP7-depleted cells also fail to elongate nascent
      daughter strand DNA following UV irradiation and show reduced DNA damage
      tolerance. We demonstrate that USP7 associates with Rad18 directly via a
      consensus USP7-binding motif and can disassemble Rad18-dependent poly-ubiquitin
      chains both in vitro and in vivo. Taken together, these observations identify
      USP7 as a novel component of the cellular DDR involved in preserving the genome
      stability. 

PMID- 25961919
TI  - Normal vs cancer thyroid stem cells: the road to transformation.
AB  - Recent investigations in thyroid carcinogenesis have led to the isolation and
      characterisation of a subpopulation of stem-like cells, responsible for tumour
      initiation, progression and metastasis. Nevertheless, the cellular origin of
      thyroid cancer stem cells (SCs) remains unknown and it is still necessary to
      define the process and the target population that sustain malignant
      transformation of tissue-resident SCs or the reprogramming of a more
      differentiated cell. Here, we will critically discuss new insights into thyroid
      SCs as a potential source of cancer formation in light of the available
      information on the oncogenic role of genetic modifications that occur during
      thyroid cancer development. Understanding the fine mechanisms that regulate
      tumour transformation may provide new ground for clinical intervention in terms
      of prevention, diagnosis and therapy. 

PMID- 25961920
TI  - How do K-RAS-activated cells evade cellular defense mechanisms?
AB  - Lung adenocarcinomas, like other cancers, develop through the accumulation of
      epigenetic and genetic alterations. Numerous studies have shown that K-RAS
      mutation is among the most important early events in carcinogenesis of the lung.
      However, it is also well established that growth-stimulating signals feed back
      into growth-suppressing pathways, and any imbalance in these signaling networks
      will cause the cell to exit the cell cycle, thereby preventing uncontrolled cell
      growth. How, then, do K-RAS-activated cells evade cellular defense mechanisms? To
      answer this question, it is necessary to identify the molecular event(s)
      responsible for the development of early dysplastic lesions that are unable to
      defend against aberrant oncogene activation. Lineage-determining transcriptional
      regulators govern differentiation status during normal lung development, as well
      as in lung adenocarcinoma. Among the genes involved in K-RAS-induced lung
      tumorigenesis, RUNX3 is unique: inactivation of Runx3 in mouse lung induces lung
      adenoma and abrogates the ARF-p53 pathway. This observation raises the
      possibility of intimate cross-talk between the differentiation program and
      oncogene surveillance. In this review, we summarized evidences suggesting that K
      RAS-activated cells do not evade cellular defense mechanisms per se; instead,
      cells with K-RAS mutations are selected only if they occur in cells in which
      defense mechanism is abrogated. 

PMID- 25961922
TI  - p38gamma MAPK is required for inflammation-associated colon tumorigenesis.
AB  - Chronic inflammation has long been considered to causatively link to colon cancer
      development. However, signal transduction pathways involved remain largely
      unidentified. Here, we report that p38gamma mitogen-activated protein kinase
      mediates inflammatory signaling to promote colon tumorigenesis. Inflammation
      activates p38gamma in mouse colon tissues and intestinal epithelial cell-specific
      p38gamma knockout (KO) attenuates colitis and inhibits pro-inflammatory cytokine
      expression. Significantly, p38gamma KO inhibits tumorigenesis in a colitis
      associated mouse model. The specific p38gamma pharmacological inhibitor
      pirfenidone also suppresses pro-inflammatory cytokine expression and colon
      tumorigenesis. The tumor-promoting activity of epithelial p38gamma was further
      demonstrated by xenograft studies. In addition, p38gamma is required for beta
      catenin/Wnt activities and p38gamma stimulates Wnt transcription by
      phosphorylating beta-catenin at Ser605. These results show that p38gamma
      activation links inflammation and colon tumorigenesis. Targeting p38gamma may be
      a novel strategy for colon cancer prevention and treatment. 

PMID- 25961921
TI  - Cancer stem cells and tumor-associated macrophages: a roadmap for multitargeting
      strategies.
AB  - The idea that tumor initiation and progression are driven by a subset of cells
      endowed with stem-like properties was first described by Rudolf Virchow in 1855.
      'Cancer stem cells', as they were termed more than a century later, represent a
      subset of tumor cells that are able to generate all tumorigenic and
      nontumorigenic cell types within the malignancy. Although their existence was
      hypothesized >150 years ago, it was only recently that stem-like cells started to
      be isolated from different neoplastic malignancies. Interestingly, Virchow, in
      suggesting a correlation between cancer and the inflammatory microenvironment,
      also paved the way for the 'Seed and Soil' theory proposed by Paget a few years
      later. Despite the time that has passed since these two important concepts were
      suggested, the relationships between Virchow's 'stem-like cells' and Paget's
      'soil' are far from being fully understood. One emerging topic is the importance
      of a stem-like niche in modulating the biological properties of stem-like cancer
      cells and thus in affecting the response of the tumor to drugs. This review aims
      to summarize the recent molecular data concerning the multilayered relationship
      between cancer stem cells and tumor-associated macrophages that form a key
      component of the tumor microenvironment. We also discuss the therapeutic
      implications of targeting this synergistic interplay. 

PMID- 25961923
TI  - MDM4/HIPK2/p53 cytoplasmic assembly uncovers coordinated repression of molecules
      with anti-apoptotic activity during early DNA damage response.
AB  - The p53 inhibitor, MDM4 (MDMX) is a cytoplasmic protein with p53-activating
      function under DNA damage conditions. Particularly, MDM4 promotes phosphorylation
      of p53 at Ser46, a modification that precedes different p53 activities. We
      investigated the mechanism by which MDM4 promotes this p53 modification and its
      consequences in untransformed mammary epithelial cells and tissues. In response
      to severe DNA damage, MDM4 stimulates p53Ser46(P) by binding and stabilizing
      serine-threonine kinase HIPK2. Under these conditions, the p53-inhibitory
      complex, MDM4/MDM2, dissociates and this allows MDM4 to promote p53/HIPK2
      functional interaction. Comparative proteomic analysis of DNA damage-treated
      cells versus -untreated cells evidenced a diffuse downregulation of proteins with
      anti-apoptotic activity, some of which were targets of p53Ser46(P)/HIPK2
      repressive activity. Importantly, MDM4 depletion abolishes the downregulation of
      these proteins indicating the requirement of MDM4 to promote p53-mediated
      transcriptional repression. Consistently, MDM4-mediated HIPK2/p53 activation
      precedes HIPK2/p53 nuclear translocation and activity. Noteworthy, repression of
      these proteins was evident also in mammary glands of mice subjected to gamma
      irradiation and was significantly enhanced in transgenic mice overexpressing
      MDM4. This study evidences the flexibility of MDM2/MDM4 heterodimer, which allows
      the development of a positive activity of cytoplasmic MDM4 towards p53-mediated
      transcriptional function. Noteworthy, this activity uncovers coordinated
      repression of molecules with shared anti-apoptotic function which precedes active
      cell apoptosis and that are frequently overexpressed and/or markers of tumour
      phenotype in human cancer. 

PMID- 25961924
TI  - hMENA(11a) contributes to HER3-mediated resistance to PI3K inhibitors in HER2
      overexpressing breast cancer cells.
AB  - Human Mena (hMENA), an actin regulatory protein of the ENA/VASP family,
      cooperates with ErbB receptor family signaling in breast cancer. It is
      overexpressed in high-risk preneoplastic lesions and in primary breast tumors
      where it correlates with HER2 overexpression and an activated status of AKT and
      MAPK. The concomitant overexpression of hMENA and HER2 in breast cancer patients
      is indicative of a worse prognosis. hMENA is expressed along with alternatively
      expressed isoforms, hMENA(11a) and hMENADeltav6 with opposite functions. A novel
      role for the epithelial-associated hMENA(11a) isoform in sustaining HER3
      activation and pro-survival pathways in HER2-overexpressing breast cancer cells
      has been identified by reverse phase protein array and validated in vivo in a
      series of breast cancer tissues. As HER3 activation is crucial in mechanisms of
      cell resistance to PI3K inhibitors, we explored whether hMENA(11a) is involved in
      these resistance mechanisms. The specific hMENA(11a) depletion switched off the
      HER3-related pathway activated by PI3K inhibitors and impaired the nuclear
      accumulation of HER3 transcription factor FOXO3a induced by PI3K inhibitors,
      whereas PI3K inhibitors activated hMENA(11a) phosphorylation and affected its
      localization. At the functional level, we found that hMENA(11a) sustains cell
      proliferation and survival in response to PI3K inhibitor treatment, whereas
      hMENA(11a) silencing increases molecules involved in cancer cell apoptosis. As
      shown in three-dimensional cultures, hMENA(11a) contributes to resistance to PI3K
      inhibition because its depletion drastically reduced cell viability upon
      treatment with PI3K inhibitor BEZ235. Altogether, these results indicate that
      hMENA(11a) in HER2-overexpressing breast cancer cells sustains HER3/AKT axis
      activation and contributes to HER3-mediated resistance mechanisms to PI3K
      inhibitors. Thus, hMENA(11a) expression can be proposed as a marker of HER3
      activation and resistance to PI3K inhibition therapies, to select patients who
      may benefit from these combined targeted treatments. hMENA(11a) activity could
      represent a new target for antiproliferative therapies in breast cancer. 

PMID- 25961925
TI  - TGF-beta1-induced EMT promotes targeted migration of breast cancer cells through
      the lymphatic system by the activation of CCR7/CCL21-mediated chemotaxis.
AB  - Tumor cells frequently disseminate through the lymphatic system during metastatic
      spread of breast cancer and many other types of cancer. Yet it is not clear how
      tumor cells make their way into the lymphatic system and how they choose between
      lymphatic and blood vessels for migration. Here we report that mammary tumor
      cells undergoing epithelial-mesenchymal transition (EMT) in response to
      transforming growth factor-beta (TGF-beta1) become activated for targeted
      migration through the lymphatic system, similar to dendritic cells (DCs) during
      inflammation. EMT cells preferentially migrated toward lymphatic vessels compared
      with blood vessels, both in vivo and in 3D cultures. A mechanism of this targeted
      migration was traced to the capacity of TGF-beta1 to promote CCR7/CCL21-mediated
      crosstalk between tumor cells and lymphatic endothelial cells. On one hand, TGF
      beta1 promoted CCR7 expression in EMT cells through p38 MAP kinase-mediated
      activation of the JunB transcription factor. Blockade of CCR7, or treatment with
      a p38 MAP kinase inhibitor, reduced lymphatic dissemination of EMT cells in
      syngeneic mice. On the other hand, TGF-beta1 promoted CCL21 expression in
      lymphatic endothelial cells. CCL21 acted in a paracrine fashion to mediate
      chemotactic migration of EMT cells toward lymphatic endothelial cells. The
      results identify TGF-beta1-induced EMT as a mechanism, which activates tumor
      cells for targeted, DC-like migration through the lymphatic system. Furthermore,
      it suggests that p38 MAP kinase inhibition may be a useful strategy to inhibit
      EMT and lymphogenic spread of tumor cells. 

PMID- 25961926
TI  - CXCL12/CXCR4: a symbiotic bridge linking cancer cells and their stromal neighbors
      in oncogenic communication networks.
AB  - Increasing evidence indicates that the tumor microenvironment has critical roles
      in all aspects of cancer biology, including growth, angiogenesis, metastasis and
      progression. Although chemokines and their receptors were originally identified
      as mediators of inflammatory diseases, it is being increasingly recognized that
      they serve as critical communication bridges between tumor cells and stromal
      cells to create a permissive microenvironment for tumor growth and metastasis.
      Thus, an important therapeutic strategy for cancer is to break this communication
      channel and isolate tumor cells for long-term elimination. Cytokine CXCL12 (also
      known as stromal-derived factor 1alpha) and its receptor CXCR4 represent the most
      promising actionable targets for this strategy. Both are overexpressed in various
      cancer types, and this aberrant expression strongly promotes proliferation,
      migration and invasion through multiple signal pathways. Several molecules that
      target CXCL12 or CXCR4 have been developed to interfere with tumor growth and
      metastasis. In this article, we review our current understanding of the
      CXCL12/CXCR4 axis in cancer tumorigenesis and progression and discuss its
      therapeutic implications. 

PMID- 25961927
TI  - The BET bromodomain inhibitor JQ1 suppresses growth of pancreatic ductal
      adenocarcinoma in patient-derived xenograft models.
AB  - The primary aim of this study was to evaluate the antitumor efficacy of the
      bromodomain inhibitor JQ1 in pancreatic ductal adenocarcinoma (PDAC) patient
      derived xenograft (tumorgraft) models. A secondary aim of the study was to
      evaluate whether JQ1 decreases expression of the oncogene c-Myc in PDAC tumors,
      as has been reported for other tumor types. We used five PDAC tumorgraft models
      that retain specific characteristics of tumors of origin to evaluate the
      antitumor efficacy of JQ1. Tumor-bearing mice were treated with JQ1 (50 mg/kg
      daily for 21 or 28 days). Expression analyses were performed with tumors
      harvested from host mice after treatment with JQ1 or vehicle control. An nCounter
      PanCancer Pathways Panel (NanoString Technologies) of 230 cancer-related genes
      was used to identify gene products affected by JQ1. Quantitative RT-PCR,
      immunohistochemistry and immunoblots were carried out to confirm that changes in
      RNA expression reflected changes in protein expression. JQ1 inhibited the growth
      of all five tumorgraft models (P<0.05), each of which harbors a KRAS mutation;
      but induced no consistent change in expression of c-Myc protein. Expression
      profiling identified CDC25B, a regulator of cell cycle progression, as one of the
      three RNA species (TIMP3, LMO2 and CDC25B) downregulated by JQ1 (P<0.05).
      Inhibition of tumor progression was more closely related to decreased expression
      of nuclear CDC25B than to changes in c-Myc expression. JQ1 and other agents that
      inhibit the function of proteins with bromodomains merit further investigation
      for treating PDAC tumors. Work is ongoing in our laboratory to identify effective
      drug combinations that include JQ1.

PMID- 25961928
TI  - Paclitaxel targets FOXM1 to regulate KIF20A in mitotic catastrophe and breast
      cancer paclitaxel resistance.
AB  - FOXM1 has been implicated in taxane resistance, but the molecular mechanism
      involved remains elusive. In here, we show that FOXM1 depletion can sensitize
      breast cancer cells and mouse embryonic fibroblasts into entering paclitaxel
      induced senescence, with the loss of clonogenic ability, and the induction of
      senescence-associated beta-galactosidase activity and flat cell morphology. We
      also demonstrate that FOXM1 regulates the expression of the microtubulin
      associated kinesin KIF20A at the transcriptional level directly through a
      Forkhead response element (FHRE) in its promoter. Similar to FOXM1, KIF20A
      expression is downregulated by paclitaxel in the sensitive MCF-7 breast cancer
      cells and deregulated in the paclitaxel-resistant MCF-7Tax(R) cells. KIF20A
      depletion also renders MCF-7 and MCF-7Tax(R) cells more sensitive to paclitaxel
      induced cellular senescence. Crucially, resembling paclitaxel treatment,
      silencing of FOXM1 and KIF20A similarly promotes abnormal mitotic spindle
      morphology and chromosome alignment, which have been shown to induce mitotic
      catastrophe-dependent senescence. The physiological relevance of the regulation
      of KIF20A by FOXM1 is further highlighted by the strong and significant
      correlations between FOXM1 and KIF20A expression in breast cancer patient
      samples. Statistical analysis reveals that both FOXM1 and KIF20A protein and mRNA
      expression significantly associates with poor survival, consistent with a role of
      FOXM1 and KIF20A in paclitaxel action and resistance. Collectively, our findings
      suggest that paclitaxel targets the FOXM1-KIF20A axis to drive abnormal mitotic
      spindle formation and mitotic catastrophe and that deregulated FOXM1 and KIF20A
      expression may confer paclitaxel resistance. These findings provide insights into
      the underlying mechanisms of paclitaxel resistance and have implications for the
      development of predictive biomarkers and novel chemotherapeutic strategies for
      paclitaxel resistance. 

PMID- 25961929
TI  - Identification of therapeutic targets for glioblastoma by network analysis.
AB  - Glioblastoma can originate from terminally differentiated astrocytes and neurons,
      which can dedifferentiate to a stem cell-like state upon transformation. In this
      study, we confirmed that transformed dedifferentiated astrocytes and neurons
      acquired a stem/progenitor cell state, although they still retained gene
      expression memory from their parental cell. Transcriptional network analysis on
      these cells identified upregulated genes in three main pathways: Wnt signaling,
      cell cycle and focal adhesion with the gene Spp1, also known as osteopontin (OPN)
      serving as a key common node connecting these three pathways. Inhibition of OPN
      blocked the formation of neurospheres, affected the proliferative capacity of
      transformed neurons and reduced the expression levels of neural stem cell
      markers. Specific inhibition of OPN in both murine and human glioma tumors
      prolonged mice survival. We conclude that OPN is an important player in
      dedifferentiation of cells during tumor formation, hence its inhibition can be a
      therapeutic target for glioblastoma. 

PMID- 25961930
TI  - Oncolytic reovirus induces intracellular redistribution of Ras to promote
      apoptosis and progeny virus release.
AB  - Reovirus is a naturally oncolytic virus that preferentially replicates in Ras
      transformed cells and is currently undergoing clinical trials as a cancer
      therapeutic. Ras transformation promotes reovirus oncolysis by enhancing virion
      disassembly during entry, viral progeny production, and virus release through
      apoptosis; however, the mechanism behind the latter is not well understood. Here,
      we show that reovirus alters the intracellular location of oncogenic Ras to
      induce apoptosis of H-RasV12-transformed fibroblasts. Reovirus infection
      decreases Ras palmitoylation levels and causes accumulation of Ras in the Golgi
      through Golgi fragmentation. With the Golgi being the site of Ras palmitoylation,
      treatment of target cells with the palmitoylation inhibitor, 2-bromopalmitate
      (2BP), prompts a greater accumulation of H-RasV12 in the Golgi, and a dose
      dependent increase in progeny virus release and subsequent spread. Conversely,
      tethering H-RasV12 to the plasma membrane (thereby preventing its movement to the
      Golgi) allows for efficient virus production, but results in basal levels of
      reovirus-induced cell death. Analysis of Ras downstream signaling reveals that
      cells expressing cycling H-RasV12 have elevated levels of phosphorylated JNK (c
      Jun N-terminal kinase), and that Ras retained at the Golgi body by 2BP increases
      activation of the MEKK1/MKK4/JNK signaling pathway to promote cell death.
      Collectively, our data suggest that reovirus induces Golgi fragmentation of
      target cells, and the subsequent accumulation of oncogenic Ras in the Golgi body
      initiates apoptotic signaling events required for virus release and spread. 

PMID- 25961931
TI  - Direct relationship between the level of p53 stabilization induced by rRNA
      synthesis-inhibiting drugs and the cell ribosome biogenesis rate.
AB  - Many drugs currently used in chemotherapy work by hindering the process of
      ribosome biogenesis. In tumors with functional p53, the inhibition of ribosome
      biogenesis may contribute to the efficacy of this treatment by inducing p53
      stabilization. As the level of stabilized p53 is critical for the induction of
      cytotoxic effects, it seems useful to highlight those cancer cell characteristics
      that can predict the degree of p53 stabilization following the treatment with
      inhibitors of ribosome biogenesis. In the present study we exposed a series of
      p53 wild-type human cancer cell lines to drugs such as actinomycin D (ActD),
      doxorubicin, 5-fluorouracil and CX-5461, which hinder ribosomal RNA (rRNA)
      synthesis. We found that the amount of stabilized p53 was directly related to the
      level of ribosome biogenesis in cells before the drug treatment. This was due to
      different levels of inactivation of the ribosomal proteins-MDM2 pathway of p53
      digestion. Inhibition of rRNA synthesis always caused cell cycle arrest,
      independent of the ribosome biogenesis rate of the cells, whereas apoptosis
      occurred only in cells with a high rDNA transcription rate. The level of p53
      stabilization induced by drugs acting in different ways from the inhibition of
      ribosome biogenesis, such as hydroxyurea (HU) and nutlin-3, was independent of
      the level of ribosome biogenesis in cells and always lower than that occurring
      after the inhibition of rRNA synthesis. Interestingly, in cells with a low
      ribosome biogenesis rate, the combined treatment with ActD and HU exerted an
      additive effect on p53 stabilization. These results indicated that (i) drugs
      inhibiting ribosome biogenesis may be highly effective in p53 wild-type cancers
      with a high ribosome biogenesis rate, as they induce apoptotic cell death, and
      (ii) the combination of drugs capable of stabilizing p53 through different
      mechanisms may be useful for treating cancers with a low ribosome biogenesis
      rate. 

PMID- 25961932
TI  - H3K9me3 facilitates hypoxia-induced p53-dependent apoptosis through repression of
      APAK.
AB  - Regions of hypoxia occur in most solid tumors, and they are associated with a
      poor prognostic outcome. Despite the absence of detectable DNA damage, severe
      hypoxia (<0.1% O2) induces a DNA damage response, including the activation of p53
      and subsequent induction of p53-dependent apoptosis. Factors affecting hypoxia
      induced p53-dependent apoptosis are unclear. Here we asked whether H3K9me3,
      through mediating gene repression, could regulate hypoxia-induced p53-dependent
      apoptosis. Under hypoxic conditions, increases in H3K9me3 occur in an oxygen
      dependent but HIF-1-independent manner. We demonstrate that under hypoxic
      conditions, which induce p53 activity, the negative regulator of p53, APAK, is
      repressed by increases in H3K9me3 along the APAK loci. APAK repression in hypoxia
      is mediated by the methyltransferase SETDB1 but not Suv39h1 or G9a.
      Interestingly, increasing hypoxia-induced H3K9me3 through pharmacological
      inhibition of JMJD2 family members leads to an increase in apoptosis and
      decreased clonogenic survival and again correlates with APAK expression. The
      relevance of understanding the mechanisms of APAK expression regulation to human
      disease was suggested by analysis of patients with colorectal cancer, which
      demonstrates that high APAK expression correlates with poor prognosis. Together,
      these data demonstrate the functional importance of H3K9me3 in hypoxia, and they
      provide a novel mechanistic link between H3K9me3, p53 and apoptosis in
      physiologically relevant conditions of hypoxia. 

PMID- 25961933
TI  - Inhibition of vacuolar ATPase subunit in tumor cells delays tumor growth by
      decreasing the essential macrophage population in the tumor microenvironment.
AB  - In cancer cells, vacuolar ATPase (V-ATPase), a multi-subunit enzyme, is expressed
      on the plasma as well as vesicular membranes and critically influences metastatic
      behavior. The soluble, cleaved N-terminal domain of V-ATPase a2 isoform is
      associated with in vitro induction of tumorigenic characteristics in macrophages.
      This activity led us to further investigate its in vivo role in cancer
      progression by inhibition of a2 isoform (a2V) in tumor cells and the concomitant
      effect on tumor microenvironment in the mouse 4T-1 breast cancer model. Results
      showed that macrophages cocultivated with a2V knockdown (sh-a2) 4T-1 cells
      produce lower amounts of tumorigenic factors in vitro and have reduced ability to
      suppress T-cell activation and proliferation compared with control 4T-1 cells.
      Data analysis showed a delayed mammary tumor growth in Balb/c mice inoculated
      with sh-a2 4T-1 cells compared with control. The purified CD11b(+) macrophages
      from sh-a2 tumors showed a reduced expression of mannose receptor-1 (CD206),
      interleukin-10, transforming growth factor-beta, arginase-1, matrix
      metalloproteinase and vascular endothelial growth factor. Flow cytometric
      analysis of tumor-infiltrated macrophages showed a significantly low number of
      F4/80(+)CD11c(+)CD206(+) macrophages in sh-a2 tumors compared with control. In sh
      a2 tumors, most of the macrophages were F4/80(+)CD11c(+) (antitumor M1
      macrophages) suggesting it to be the reason behind delayed tumor growth.
      Additionally, tumor-infiltrating macrophages from sh-a2 tumors showed a reduced
      expression of CD206 compared with control whereas CD11c expression was
      unaffected. These findings demonstrate that in the absence of a2V in tumor cells,
      the resident macrophage population in the tumor microenvironment is altered which
      affects in vivo tumor growth. We suggest that by involving the host immune
      system, tumor growth can be controlled through targeting of a2V on tumor cells. 

PMID- 25961934
TI  - Repression of TIF1gamma by SOX2 promotes TGF-beta-induced epithelial-mesenchymal
      transition in non-small-cell lung cancer.
AB  - TIF1gamma is a novel regulator of transforming growth factor (TGF)-beta/Smad
      signaling. Our previous studies show that dysregulated expression of
      transcriptional intermediary factor 1 gamma (TIF1gamma) and abnormal TGF
      beta/Smad signaling are implicated in non-small-cell lung cancer (NSCLC)
      separately. However, how TIF1gamma contributes to NSCLC by controlling TGF
      beta/Smad signaling is poorly understood. Here, we investigated the mechanistic
      role of TIF1gamma in TGF-beta-induced epithelial-mesenchymal transition (EMT), as
      well as a link between TIF1gamma and SOX2 in NSCLC. We show that TIF1gamma is a
      downstream target of SOX2 in NSCLC cells. SOX2 overexpression negatively
      regulated TIF1gamma promoter activity and thereby attenuated TIF1gamma mRNA and
      protein expression levels; SOX2 knockdown significantly enhanced TIF1gamma
      promoter activity and augmented TIF1gamma expression. Moreover, TIF1gamma mRNA
      expression was downregulated in human NSCLC tissues and negatively correlated
      with SOX2 protein, which was upregulated in NSCLC tissues. Importantly, knockdown
      of TIF1gamma or SOX2 overexpression augmented SMAD4 (human Mad (mothers against
      decapentaplegic)-related homologous protein 4)-dependent transcriptional
      responses, and enhanced TGF-beta-induced EMT and human NSCLC cell invasion;
      knockdown of SOX2 impaired TGF-beta-induced EMT and NSCLC cell invasion. In an in
      vivo model of metastasis, knockdown of TIF1gamma promotes NSCLC cell metastasis.
      In addition, our data suggested that TIF1gamma inhibited TGF-beta-induced EMT
      through competing with SMAD4 in NSCLC cells. Taken together, our findings reveal
      a new mechanism by which SOX2-mediated transcription repression of TIF1gamma
      promotes TGF-beta-induced EMT in NSCLC. 

PMID- 25961935
TI  - Mechanism of action of a WWTR1(TAZ)-CAMTA1 fusion oncoprotein.
AB  - The WWTR1 (protein is known as TAZ)-CAMTA1 (WC) fusion gene defines epithelioid
      hemangioendothelioma, a malignant vascular cancer. TAZ (transcriptional
      coactivator with PDZ binding motif) is a transcriptional coactivator and end
      effector of the Hippo tumor suppressor pathway. It is inhibited by
      phosphorylation by the Hippo kinases LATS1 and LATS2. Such phosphorylation causes
      cytoplasmic localization, 14-3-3 protein binding and the phorphorylation of a
      terminal phosphodegron promotes ubiquitin-dependent degradation (the
      phosphorylation of the different motifs has several effects). CAMTA1 is a
      putative tumor suppressive transcription factor. Here we demonstrate that TAZ
      CAMTA1 (TC) fusion results in its nuclear localization and constitutive
      activation. Consequently, cells expressing TC display a TAZ-like transcriptional
      program that causes resistance to anoikis and oncogenic transformation. Our
      findings elucidate the mechanistic basis of TC oncogenic properties, highlight
      that TC is an important model to understand how the Hippo pathway can be
      inhibited in cancer, and provide approaches for targeting this chimeric protein. 

PMID- 25961936
TI  - STAT3 integrates cooperative Ras and TGF-beta signals that induce Snail
      expression.
AB  - The epithelial-mesenchymal transition (EMT) is a crucial morphological event that
      occurs during the progression of epithelial tumors. EMT can be induced by
      transforming growth factor beta (TGF-beta) in certain kinds of cancer cells
      through the induction of Snail, a key regulator of EMT. We have previously found
      that TGF-beta remarkably induces Snail expression in cooperation with Ras
      signals; however, the underlying mechanism of this synergism has not yet been
      determined. Here, we demonstrate that signal transducer and activator of
      transcription 3 (STAT3) acts as a mediator that synergizes TGF-beta and Ras
      signals. The overexpression of STAT3 enhanced Snail induction, whereas siRNA
      mediated knockdown of STAT3 inhibited it. The STAT3-YF mutant, which has Tyr 705
      substituted with Phe, did not enhance Snail induction. Several STAT3 mutants
      lacking transcriptional activity also failed to enhance it; however, the putative
      STAT3-binding elements in the Snail promoter regions were not required for STAT3
      mediated Snail induction. Protein inhibitor of activated STAT3 (PIAS3) inhibited
      the enhanced Snail promoter activity induced by TGF-beta and Ras. The interaction
      between PIAS3 and STAT3 was reduced by TGF-beta in cells harboring oncogenic Ras,
      whereas TGF-beta promoted the binding of PIAS3 to Smad3, a crucial mediator of
      TGF-beta signaling. Therefore, these findings suggest that STAT3 enhances Snail
      induction when it is dissociated from PIAS3 by TGF-beta in cooperation with Ras
      signals. 

PMID- 25961937
TI  - Optical Dark-Field and Electron Energy Loss Imaging and Spectroscopy of Symmetry
      Forbidden Modes in Loaded Nanogap Antennas.
AB  - We have produced large numbers of hybrid metal-semiconductor nanogap antennas
      using a scalable electrochemical approach and systematically characterized the
      spectral and spatial character of their plasmonic modes with optical dark-field
      scattering, electron energy loss spectroscopy with principal component analysis,
      and full wave simulations. The coordination of these techniques reveal that these
      nanostructures support degenerate transverse modes which split due to substrate
      interactions, a longitudinal mode which scales with antenna length, and a
      symmetry-forbidden gap-localized transverse mode. This gap-localized transverse
      mode arises from mode splitting of transverse resonances supported on both
      antenna arms and is confined to the gap load enabling (i) delivery of substantial
      energy to the gap material and (ii) the possibility of tuning the antenna
      resonance via active modulation of the gap material's optical properties. The
      resonant position of this symmetry-forbidden mode is sensitive to gap size,
      dielectric strength of the gap material, and is highly suppressed in air-gapped
      structures which may explain its absence from the literature to date.
      Understanding the complex modal structure supported on hybrid nanosystems is
      necessary to enable the multifunctional components many seek. 

PMID- 25961938
TI  - Structural basis for a six nucleotide genetic alphabet.
AB  - Expanded genetic systems are most likely to work with natural enzymes if the
      added nucleotides pair with geometries that are similar to those displayed by
      standard duplex DNA. Here, we present crystal structures of 16-mer duplexes
      showing this to be the case with two nonstandard nucleobases (Z, 6-amino-5-nitro
      2(1H)-pyridone and P, 2-amino-imidazo[1,2-a]-1,3,5-triazin-4(8H)one) that were
      designed to form a Z:P pair with a standard "edge on" Watson-Crick geometry, but
      joined by rearranged hydrogen bond donor and acceptor groups. One duplex, with
      four Z:P pairs, was crystallized with a reverse transcriptase host and adopts
      primarily a B-form. Another contained six consecutive Z:P pairs; it crystallized
      without a host in an A-form. In both structures, Z:P pairs fit canonical
      nucleobase hydrogen-bonding parameters and known DNA helical forms. Unique
      features include stacking of the nitro group on Z with the adjacent nucleobase
      ring in the A-form duplex. In both B- and A-duplexes, major groove widths for the
      Z:P pairs are approximately 1 A wider than those of comparable G:C pairs, perhaps
      to accommodate the large nitro group on Z. Otherwise, ZP-rich DNA had many of the
      same properties as CG-rich DNA, a conclusion supported by circular dichroism
      studies in solution. The ability of standard duplexes to accommodate multiple and
      consecutive Z:P pairs is consistent with the ability of natural polymerases to
      biosynthesize those pairs. This, in turn, implies that the GACTZP synthetic
      genetic system can explore the entire expanded sequence space that additional
      nucleotides create, a major step forward in this area of synthetic biology. 

PMID- 25961940
TI  - The genomic landscape of high hyperdiploid childhood acute lymphoblastic
      leukemia.
AB  - High hyperdiploid (51-67 chromosomes) acute lymphoblastic leukemia (ALL) is one
      of the most common childhood malignancies, comprising 30% of all pediatric B cell
      precursor ALL. Its characteristic genetic feature is the nonrandom gain of
      chromosomes X, 4, 6, 10, 14, 17, 18 and 21, with individual trisomies or
      tetrasomies being seen in over 75% of cases, but the pathogenesis remains poorly
      understood. We performed whole-genome sequencing (WGS) (n = 16) and/or whole
      exome sequencing (WES) (n = 39) of diagnostic and remission samples from 51 cases
      of high hyperdiploid ALL to further define the genomic landscape of this
      malignancy. The majority of cases showed involvement of the RTK-RAS pathway and
      of histone modifiers. No recurrent fusion gene-forming rearrangement was found,
      and an analysis of mutations on trisomic chromosomes indicated that the
      chromosomal gains were early events, strengthening the notion that the high
      hyperdiploid pattern is the main driver event in this common pediatric
      malignancy. 

PMID- 25961939
TI  - A Sleeping Beauty forward genetic screen identifies new genes and pathways
      driving osteosarcoma development and metastasis.
AB  - Osteosarcomas are sarcomas of the bone, derived from osteoblasts or their
      precursors, with a high propensity to metastasize. Osteosarcoma is associated
      with massive genomic instability, making it problematic to identify driver genes
      using human tumors or prototypical mouse models, many of which involve loss of
      Trp53 function. To identify the genes driving osteosarcoma development and
      metastasis, we performed a Sleeping Beauty (SB) transposon-based forward genetic
      screen in mice with and without somatic loss of Trp53. Common insertion site
      (CIS) analysis of 119 primary tumors and 134 metastatic nodules identified 232
      sites associated with osteosarcoma development and 43 sites associated with
      metastasis, respectively. Analysis of CIS-associated genes identified numerous
      known and new osteosarcoma-associated genes enriched in the ErbB, PI3K-AKT-mTOR
      and MAPK signaling pathways. Lastly, we identified several oncogenes involved in
      axon guidance, including Sema4d and Sema6d, which we functionally validated as
      oncogenes in human osteosarcoma. 

PMID- 25961942
TI  - PDE3A mutations cause autosomal dominant hypertension with brachydactyly.
AB  - Cardiovascular disease is the most common cause of death worldwide, and
      hypertension is the major risk factor. Mendelian hypertension elucidates
      mechanisms of blood pressure regulation. Here we report six missense mutations in
      PDE3A (encoding phosphodiesterase 3A) in six unrelated families with mendelian
      hypertension and brachydactyly type E (HTNB). The syndrome features brachydactyly
      type E (BDE), severe salt-independent but age-dependent hypertension, an
      increased fibroblast growth rate, neurovascular contact at the rostral
      ventrolateral medulla, altered baroreflex blood pressure regulation and death
      from stroke before age 50 years when untreated. In vitro analyses of mesenchymal
      stem cell-derived vascular smooth muscle cells (VSMCs) and chondrocytes provided
      insights into molecular pathogenesis. The mutations increased protein kinase A
      mediated PDE3A phosphorylation and resulted in gain of function, with increased
      cAMP-hydrolytic activity and enhanced cell proliferation. Levels of
      phosphorylated VASP were diminished, and PTHrP levels were dysregulated. We
      suggest that the identified PDE3A mutations cause the syndrome. VSMC-expressed
      PDE3A deserves scrutiny as a therapeutic target for the treatment of
      hypertension. 

PMID- 25961941
TI  - Phylogeographical analysis of the dominant multidrug-resistant H58 clade of
      Salmonella Typhi identifies inter- and intracontinental transmission events.
AB  - The emergence of multidrug-resistant (MDR) typhoid is a major global health
      threat affecting many countries where the disease is endemic. Here whole-genome
      sequence analysis of 1,832 Salmonella enterica serovar Typhi (S. Typhi)
      identifies a single dominant MDR lineage, H58, that has emerged and spread
      throughout Asia and Africa over the last 30 years. Our analysis identifies
      numerous transmissions of H58, including multiple transfers from Asia to Africa
      and an ongoing, unrecognized MDR epidemic within Africa itself. Notably, our
      analysis indicates that H58 lineages are displacing antibiotic-sensitive
      isolates, transforming the global population structure of this pathogen. H58
      isolates can harbor a complex MDR element residing either on transmissible IncHI1
      plasmids or within multiple chromosomal integration sites. We also identify new
      mutations that define the H58 lineage. This phylogeographical analysis provides a
      framework to facilitate global management of MDR typhoid and is applicable to
      similar MDR lineages emerging in other bacterial species. 

PMID- 25961945
TI  - Exceptional and Anisotropic Transport Properties of Photocarriers in Black
      Phosphorus.
AB  - One key challenge in developing postsilicon electronic technology is to find
      ultrathin channel materials with high charge mobilities and sizable energy band
      gaps. Graphene can offer extremely high charge mobilities; however, the lack of a
      band gap presents a significant barrier. Transition metal dichalcogenides possess
      sizable and thickness-tunable band gaps; however, their charge mobilities are
      relatively low. Here we show that black phosphorus has room-temperature charge
      mobilities on the order of 10(4) cm(2) V(-1) s(-1), which are about 1 order of
      magnitude larger than silicon. We also demonstrate strong anisotropic transport
      in black phosphorus, where the mobilities along the armchair direction are about
      1 order of magnitude larger than in the zigzag direction. A photocarrier lifetime
      as long as 100 ps is also determined. These results illustrate that black
      phosphorus is a promising candidate for future electronic and optoelectronic
      applications. 

PMID- 25961944
TI  - Excess of rare, inherited truncating mutations in autism.
AB  - To assess the relative impact of inherited and de novo variants on autism risk,
      we generated a comprehensive set of exonic single-nucleotide variants (SNVs) and
      copy number variants (CNVs) from 2,377 families with autism. We find that
      private, inherited truncating SNVs in conserved genes are enriched in probands
      (odds ratio = 1.14, P = 0.0002) in comparison to unaffected siblings, an effect
      involving significant maternal transmission bias to sons. We also observe a bias
      for inherited CNVs, specifically for small (<100 kb), maternally inherited events
      (P = 0.01) that are enriched in CHD8 target genes (P = 7.4 * 10(-3)). Using a
      logistic regression model, we show that private truncating SNVs and rare,
      inherited CNVs are statistically independent risk factors for autism, with odds
      ratios of 1.11 (P = 0.0002) and 1.23 (P = 0.01), respectively. This analysis
      identifies a second class of candidate genes (for example, RIMS1, CUL7 and LZTR1)
      where transmitted mutations may create a sensitized background but are unlikely
      to be completely penetrant. 

PMID- 25961943
TI  - The impact of low-frequency and rare variants on lipid levels.
AB  - Using a genome-wide screen of 9.6 million genetic variants achieved through 1000
      Genomes Project imputation in 62,166 samples, we identify association to lipid
      traits in 93 loci, including 79 previously identified loci with new lead SNPs and
      10 new loci, 15 loci with a low-frequency lead SNP and 10 loci with a missense
      lead SNP, and 2 loci with an accumulation of rare variants. In six loci, SNPs
      with established function in lipid genetics (CELSR2, GCKR, LIPC and APOE) or
      candidate missense mutations with predicted damaging function (CD300LG and
      TM6SF2) explained the locus associations. The low-frequency variants increased
      the proportion of variance explained, particularly for low-density lipoprotein
      cholesterol and total cholesterol. Altogether, our results highlight the impact
      of low-frequency variants in complex traits and show that imputation offers a
      cost-effective alternative to resequencing. 

PMID- 25961946
TI  - Effect of Melatonin on the Extracellular-Regulated Kinase Signal Pathway
      Activation and Human Osteoblastic Cell Line hFOB 1.19 Proliferation.
AB  - It has been shown that melatonin may affect bone metabolism. However, it is
      controversial whether melatonin could promote osteoblast proliferation, and the
      precise molecular mechanism of melatonin on osteoblast proliferation is still
      obscure. In this study, the results of the CCK-8 assay showed that melatonin
      significantly promoted human osteoblastic cell line hFOB 1.19 cell proliferation
      at 1, 2.5, 5, 10, 25, 50 and 100 uM concentrations for 24 h, but there were no
      significant differences among the groups. Western blot demonstrated that 10 uM
      melatonin significantly promoted ERK1/2 phosphorylation. Furthermore, we also
      detected the phosphorylation of c-Raf, MEK1/2, p90RSK and MSK1, and all of them
      increased with 10 uM melatonin. U0126 (a selective inhibitor of MEK that disrupts
      downstream activation of ERK1/2) downregulated the phosphorylation of ERK1/2,
      p90RSK and MSK1. U0126 also attenuated the proliferation of osteoblasts
      stimulated by melatonin. In conclusion, this study for the first time indicates
      that melatonin (10 nM-100 uM) promotes the proliferation of a human osteoblastic
      cell line hFOB 1.19 through activation of c-Raf, MEK1/2, ERK1/2, p90RSK and MSK1.

PMID- 25961947
TI  - Optimal decision rules for biomarker-based subgroup selection for a targeted
      therapy in oncology.
AB  - Throughout recent years, there has been a rapidly increasing interest regarding
      the evaluation of so-called targeted therapies. These therapies are assumed to
      show a greater benefit in a pre-specified subgroup of patients-commonly
      identified by a predictive biomarker-as compared to the total patient population
      of interest. This situation has led to the necessity to develop biostatistical
      methods allowing an efficient evaluation of such treatments. Among others,
      adaptive enrichment designs have been proposed as a solution. These designs allow
      the selection of the most promising patient population based on an efficacy
      analysis at interim and restricting recruitment to these patients afterwards. As
      has recently been shown, the performance of the applied interim decision rule in
      such a design plays a crucial role in ensuring a successful trial. In this work,
      we investigate the situation when the primary outcome of the trial is a binary
      variable. Optimal decision rules are derived which incorporate the uncertainty
      about the treatment effects. These optimal decision rules are evaluated with
      respect to their performance in an adaptive enrichment design in terms of correct
      selection probability and power, and are compared to proposed ad hoc decision
      rules. Our methods are illustrated by means of a clinical trial example. 

PMID- 25961948
TI  - Identification and Validation of Evolutionarily Conserved Unusually Short Pre
      mRNA Introns in the Human Genome.
AB  - According to the length distribution of human introns, there is a large
      population of short introns with a threshold of 65 nucleotides (nt) and a peak at
      85 nt. Using human genome and transcriptome databases, we investigated the
      introns shorter than 66 nt, termed ultra-short introns, the identities of which
      are scarcely known. Here, we provide for the first time a list of bona fide human
      ultra-short introns, which have never been characterized elsewhere. By conducting
      BLAST searches of the databases, we screened 22 introns (37-65 nt) with conserved
      lengths and sequences among closely related species. We then provide experimental
      and bioinformatic evidence for the splicing of 15 introns, of which 12 introns
      were remarkably G-rich and 9 introns contained completely inefficient splice
      sites and/or branch sites. These unorthodox characteristics of ultra-short
      introns suggest that there are unknown splicing mechanisms that differ from the
      well-established mechanism. 

PMID- 25961949
TI  - Subcellular Sequestration and Impact of Heavy Metals on the Ultrastructure and
      Physiology of the Multicellular Freshwater Alga Desmidium swartzii.
AB  - Due to modern life with increasing traffic, industrial production and
      agricultural practices, high amounts of heavy metals enter ecosystems and pollute
      soil and water. As a result, metals can be accumulated in plants and particularly
      in algae inhabiting peat bogs of low pH and high air humidity. In the present
      study, we investigated the impact and intracellular targets of aluminum, copper,
      cadmium, chromium VI and zinc on the filamentous green alga Desmidium swartzii,
      which is an important biomass producer in acid peat bogs. By means of
      transmission electron microscopy (TEM) and electron energy loss spectroscopy
      (EELS) it is shown that all metals examined are taken up into Desmidium readily,
      where they are sequestered in cell walls and/or intracellular compartments. They
      cause effects on cell ultrastructure to different degrees and additionally
      disturb photosynthetic activity and biomass production. Our study shows a clear
      correlation between toxicity of a metal and the ability of the algae to
      compartmentalize it intracellularly. Cadmium and chromium, which are not
      compartmentalized, exert the most toxic effects. In addition, this study shows
      that the filamentous alga Desmidium reacts more sensitively to aluminum and zinc
      when compared to its unicellular relative Micrasterias, indicating a severe
      threat to the ecosystem. 

PMID- 25961950
TI  - TCF4 Is a Molecular Target of Resveratrol in the Prevention of Colorectal Cancer.
AB  - The Wnt/beta-catenin pathway plays an essential role in the tumorigenesis of
      colorectal cancer. T-cell factor-4 (TCF4) is a member of the TCF/LEF (lymphoid
      enhancer factor) family of transcription factors, and dysregulation of beta
      catenin is decisive for the initiation and progression of colorectal cancer.
      However, the role of TCF4 in the transcriptional regulation of its target gene
      remained poorly understood. Resveratrol is a dietary phytoalexin and present in
      many plants, including grape skin, nuts and fruits. Although resveratrol has been
      widely implicated in anti-tumorigenic and pro-apoptotic properties in several
      cancer models, the underlying cellular mechanisms are only partially understood.
      The current study was performed to elucidate the molecular mechanism of the anti
      cancer activity of resveratrol in human colorectal cancer cells. The treatment of
      resveratrol and other phytochemicals decreased the expression of TCF4.
      Resveratrol decreases cellular accumulation of exogenously-introduced TCF4
      protein, but did not change the TCF4 transcription. The inhibition of proteasomal
      degradation using MG132 (carbobenzoxy-Leu-Leu-leucinal) and lactacystin
      ameliorates resveratrol-stimulated down-regulation of TCF4. The half-life of TCF4
      was decreased in the cells exposed to resveratrol. Resveratrol increased
      phosphorylation of TCF4 at serine/threonine residues through ERK (extracellular
      signal-regulated kinases) and p38-dependent pathways. The TCF4 knockdown
      decreased TCF/beta-catenin-mediated transcriptional activity and sensitized
      resveratrol-induced apoptosis. The current study provides a new mechanistic link
      between resveratrol and TCF4 down-regulation and significant benefits for further
      preclinical and clinical practice. 

PMID- 25961951
TI  - Humic Acid Increases Amyloid beta-Induced Cytotoxicity by Induction of ER Stress
      in Human SK-N-MC Neuronal Cells.
AB  - Humic acid (HA) is a possible etiological factor associated with for several
      vascular diseases. It is known that vascular risk factors can directly increase
      the susceptibility to Alzheimer's disease (AD), which is a neurodegenerative
      disorder due to accumulation of amyloid beta (Abeta) peptide in the brain.
      However, the role that HA contributes to Abeta-induced cytotoxicity has not been
      demonstrated. In the present study, we demonstrate that HA exhibits a synergistic
      effect enhancing Abeta-induced cytotoxicity in cultured human SK-N-MC neuronal
      cells. Furthermore, this deterioration was mediated through the activation of
      endoplasmic reticulum (ER) stress by stimulating PERK and eIF2alpha
      phosphorylation. We also observed HA and Abeta-induced cytotoxicity is associated
      with mitochondrial dysfunction caused by down-regulation of the Sirt1/PGC1alpha
      pathway, while in contrast, treating the cells with the ER stress inhibitor
      Salubrinal, or over-expression of Sirt1 significantly reduced loss of cell
      viability by HA and Abeta. Our findings suggest a new mechanism by which HA can
      deteriorate Abeta-induced cytotoxicity through modulation of ER stress, which may
      provide significant insights into the pathogenesis of AD co-occurring with
      vascular injury. 

PMID- 25961952
TI  - 5-ALA Fluorescence Image Guided Resection of Glioblastoma Multiforme: A Meta
      Analysis of the Literature.
AB  - BACKGROUND: Glioblastoma multiforme (GBM) is one of the most deadly cancers in
      humans. Despite recent advances in anti-cancer therapies, most patients with GBM
      die from local disease progression. Fluorescence image guided surgical resection
      (FIGR) was recently advocated to enhance local control of GBM. This is meta
      analyses of 5-aminolevulinic (5-ALA) induced FIGR. MATERIALS: Review of the
      literature produced 503 potential publications; only 20 of these fulfilled the
      inclusion criteria of this analysis, including a total of 565 patients treated
      with 5-ALA-FIGR reporting on its outcomes and 800 histological samples reporting
      5-ALA-FIGR sensitivity and specificity. RESULTS: The mean gross total resection
      (GTR) rate was 75.4% (95% CI: 67.4-83.5, p<0.001). The mean time to tumor
      progression (TTP) was 8.1 months (95% CI: 4.7-12, p<0.001). The mean overall
      survival gain reported was 6.2 months (95% CI: -1-13, p<0.001). The specificity
      was 88.9% (95% CI: 83.9-93.9, p<0.001) and the sensitivity was 82.6% (95% CI:
      73.9-91.9, p<0.001). CONCLUSION: 5-ALA-FIGR in GBM is highly sensitive and
      specific, and imparts significant benefits to patients in terms of improved GTR
      and TTP.

PMID- 25961953
TI  - 4,4'-Diisothiocyanostilbene-2,2'-disulfonic Acid (DIDS) Ameliorates Ischemia
      Hypoxia-Induced White Matter Damage in Neonatal Rats through Inhibition of the
      Voltage-Gated Chloride Channel ClC-2.
AB  - Chronic cerebral hypoperfusion is believed to cause white matter lesions (WMLs),
      leading to cognitive impairment. Previous studies have shown that inflammation
      and apoptosis of oligodendrocytes (OLs) are involved in the pathogenesis of WMLs,
      but effective treatments have not been studied. In this study, 4,4'
      diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), a chloride (Cl-) channel
      blocker, was injected into chronic cerebral ischemia-hypoxia rat models at
      different time points. Our results showed that DIDS significantly reduced the
      elevated mRNA levels and protein expression of chloride channel 2 (ClC-2) in
      neonatal rats induced by ischemia-hypoxia. Meanwhile, DIDS application
      significantly decreased the concentrations of reactive oxygen species (ROS); and
      the mRNA levels of inducible nitric oxide synthase (iNOS) and tumor necrosis
      factor-alpha TNF-alpha in neonatal rats with hypoxic-ischemic damage. Myelin
      staining was weaker in neonatal rats with hypoxic-ischemic damage compared to
      normal controls in corpus callosum and other white matter, which was ameliorated
      by DIDS. Furthermore, the elevated number of caspase-3 and neural/glial antigen 2
      (NG-2) double-labeled positive cells was attenuated by DIDS after ischemia anoxic
      injury. Administration of DIDS soon after injury alleviated damage to OLs much
      more effectively in white matter. In conclusion, our study suggests that early
      application of DIDS after ischemia-hypoxia injury may partially protect
      developing OLs. 

PMID- 25961954
TI  - Investigation of the Anti-Melanogenic and Antioxidant Characteristics of
      Eucalyptus camaldulensis Flower Essential Oil and Determination of Its Chemical
      Composition.
AB  - The effects of essential oil from Eucalyptus camaldulensis flowers oil on
      melanogenesis and the oil's antioxidant characteristics were investigated. Assays
      of mushroom and cellular tyrosinase activities and melanin content of mouse
      melanoma cells were performed spectrophotometrically, and the expression of
      melanogenesis-related proteins was determined by Western blotting. The possible
      signaling pathways involved in essential oil-mediated depigmentation were also
      investigated using specific protein kinase inhibitors. The results revealed that
      E. camaldulensis flower essential oil effectively suppresses intracellular
      tyrosinase activity and decreases melanin amount in B16F10 mouse melanoma cells.
      The essential oil also exhibits antioxidant properties and effectively decreases
      intracellular reactive oxygen species (ROS) levels. The volatile chemical
      composition of the essential oil was analyzed with gas chromatography-mass
      spectrometry (GC/MS). The chemical constituents in the essential oil are
      predominately oxygenated monoterpenes (34.9%), followed by oxygenated
      sesquiterpenes (31.8%), monoterpene hydrocarbons (29.0%) and sesquiterpene
      hydrocarbons (4.3%). Our results indicated that E. camaldulensis flower essential
      oil inhibits melanogenesis through its antioxidant properties and by down
      regulating both mitogen-activated protein kinases (MAPK) and protein kinase A
      (PKA) signaling pathways. The present study indicates that the essential oil has
      the potential to be developed into a skin care product. 

PMID- 25961955
TI  - Regulative Effect of Mir-205 on Osteogenic Differentiation of Bone Mesenchymal
      Stem Cells (BMSCs): Possible Role of SATB2/Runx2 and ERK/MAPK Pathway.
AB  - Bone mesenchymal stem cells (BMSCs) have multiple potentials to differentiate
      into osteoblasts and adipocytes, and methods to enhance their osteogenic
      differentiation are gaining increasing attention. MicroRNAs are critical
      regulation factors during the process of the osteogenic induction in BMSCs, and
      mir-205 has been substantiated to be involved in the osteogenic process, but the
      underlying mechanisms remain unclear. The purpose of this article is to
      investigate the role of mir-205 in the osteogenic differentiation of BMSCs. We
      found that mir-205 expression was down-regulated in a time-dependent manner
      during BMSC osteo-induction. Inhibition of mir-205 enhanced osteogenic abilities
      by up-regulating bone sialoprotein (BSP) and osteopontin (OPN) protein levels and
      increasing alkaline phosphatase (ALP) activity and osteocalcin secretion.
      Furthermore, we found that mir-205 could regulate protein expression of special
      AT-rich sequence-binding protein 2 (SATB2) and runt-related transcription factor
      2 (Runx2), and over-expression of SATB2 activated Runx2 and reversed the negative
      effects of mir-205 on osteoblastic differentiation. Furthermore, we examined the
      extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein
      kinase (p38 MAPK) pathways during osteogenic induction and our data indicates
      that mir-205 might exert negative functions on the osteogenic differentiation in
      BMSCs at least partly via altering phosphorylation of ERK and p38 MAPK. These
      results shed new light on the molecular mechanisms of microRNAs in governing
      differentiation of BMSCs. 

PMID- 25961956
TI  - Dihydroaustrasulfone Alcohol (WA-25) Impedes Macrophage Foam Cell Formation by
      Regulating the Transforming Growth Factor-beta1 Pathway.
AB  - Atherosclerosis is considered an inflammatory disease. However, clinically used
      anti-atherosclerotic drugs, such as simvastatin, have many side effects.
      Recently, several unique marine compounds have been isolated that possess a
      variety of bioactivities. In a previous study, we found a synthetic precursor of
      the marine compound (austrasulfone), which is dihydroaustrasulfone alcohol (WA
      25), has anti-atherosclerotic effects in vivo. However, the detailed mechanisms
      remain unclear. Therefore, to clarify the mechanisms through which WA-25 exerts
      anti-atherosclerotic activity, we used RAW 264.7 macrophages as an in vitro model
      to evaluate the effects of WA-25. In lipopolysaccharide (LPS)-stimulated RAW
      264.7 cells, WA-25 significantly inhibited expression of the pro-inflammatory
      proteins, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In
      contrast, simvastatin increased the COX-2 expression compared to WA-25. In
      addition, WA-25 impedes foam cell formation and up-regulated the lysosomal and
      cyclic adenosine monophosphate (cAMP) signaling pathway. We also observed that
      transforming growth factor beta1 (TGF-beta1) was up-regulated by WA-25 and
      simvastatin in LPS-induced RAW 264.7 cells, and the promising anti
      atherosclerosis effects of WA-25 were disrupted by blockade of TGF-beta1
      signaling. Besides, WA-25 might act through increasing lipolysis than through
      alteration of lipid export. Taken together, these data demonstrate that WA-25 may
      have potential as an anti-atherosclerotic drug with anti-inflammatory effects. 

PMID- 25961958
TI  - Toxicity Assessment of 4-Methyl-1-cyclohexanemethanol and Its Metabolites in
      Response to a Recent Chemical Spill in West Virginia, USA.
AB  - The large-scale chemical spill on January 9, 2014 from coal processing and
      cleaning storage tanks of Freedom Industries in Charleston affected the drinking
      water supply to 300,000 people in Charleston, West Virginia metropolitan, while
      the short-term and long-term health impacts remain largely unknown and need to be
      assessed and monitored. There is a lack of publically available toxicological
      information for the main contaminant 4-methyl-1-cyclohexanemethanol (4-MCHM).
      Particularly, little is known about 4-MCHM metabolites and their toxicity. This
      study reports timely and original results of the mechanistic toxicity assessment
      of 4-MCHM and its metabolites via a newly developed quantitative toxicogenomics
      approach, employing proteomics analysis in yeast cells and transcriptional
      analysis in human cells. These results suggested that, although 4-MCHM is
      considered only moderately toxic based on the previous limited acute toxicity
      evaluation, 4-MCHM metabolites were likely more toxic than 4-MCHM in both yeast
      and human cells, with different toxicity profiles and potential mechanisms. In
      the yeast library, 4-MCHM mainly induced chemical stress related to transmembrane
      transport and transporter activity, while 4-MCHM metabolites of S9 mainly induced
      oxidative stress related to antioxidant activity and oxidoreductase activity.
      With human A549 cells, 4-MCHM mainly induced DNA damage-related biomarkers, which
      indicates that 4-MCHM is related to genotoxicity due to its DNA damage effect on
      human cells and therefore warrants further chronic carcinogenesis evaluation. 

PMID- 25961957
TI  - A specific nucleophilic ring-opening reaction of aziridines as a unique platform
      for the construction of hydrogen polysulfides sensors.
AB  - A hydrogen polysulfide mediated aziridine ring-opening reaction was discovered.
      Based on this reaction, a novel H2S(n)-specific chemosensor (AP) was developed.
      AP showed high sensitivity and selectivity for H2S(n). Notably, the fluorescent
      turn-on product (1) exhibited excellent two-photon photophysical properties, a
      large Stokes shift, and high solid state luminescent efficiency.

PMID- 25961961
TI  - Purification, structural characterization, and modification of organosolv wheat
      straw lignin.
AB  - Biolignin, a wheat straw lignin produced by acetic acid/formic acid/water
      hydrolysis, was characterized by (31)P and (13)C-(1)H 2D NMR spectroscopy and by
      size-exclusion chromatography. Biolignin is a mixture of low molar mass compounds
      (Mn = 1660 g/mol) made up of S, G, and H units and of coumaric and ferulic acid
      units. beta-5 and beta-O-4 interunit linkages are partially acylated in the gamma
      position by acetate and p-coumarate groups. Deacylated samples with a low content
      of contaminants were obtained by combining alkaline hydrolysis and solvent
      extraction. The high phenolic OH content found by (31)P NMR reflects the presence
      of condensed aromatic units, such as 5-5 units. Reaction of purified lignin with
      ethanol and ethane-1,2-diol yielded esterified lignins much more soluble than
      Biolignin in common organic solvents. During this reaction, the secondary OH of
      beta-O-4 linkages was simultaneously etherified. Phenol hydroxyethylation by 2
      chloroethanol yielded samples containing only aliphatic hydroxyl groups. 

PMID- 25961960
TI  - N-Substituted Quinolinonyl Diketo Acid Derivatives as HIV Integrase Strand
      Transfer Inhibitors and Their Activity against RNase H Function of Reverse
      Transcriptase.
AB  - Bifunctional quinolinonyl DKA derivatives were first described as nonselective
      inhibitors of 3'-processing (3'-P) and strand transfer (ST) functions of HIV-1
      integrase (IN), while 7-aminosubstituted quinolinonyl derivatives were proven IN
      strand transfer inhibitors (INSTIs) that also displayed activity against
      ribonuclease H (RNase H). In this study, we describe the design, synthesis, and
      biological evaluation of new quinolinonyl diketo acid (DKA) derivatives
      characterized by variously substituted alkylating groups on the nitrogen atom of
      the quinolinone ring. Removal of the second DKA branch of bifunctional DKAs, and
      the amino group in position 7 of quinolinone ring combined with a fine-tuning of
      the substituents on the benzyl group in position 1 of the quinolinone, increased
      selectivity for IN ST activity. In vitro, the most potent compound was 11j (IC50
      = 10 nM), while the most active compounds against HIV infected cells were ester
      derivatives 10j and 10l. In general, the activity against RNase H was negligible,
      with only a few compounds active at concentrations higher than 10 MUM. The
      binding mode of the most potent IN inhibitor 11j within the IN catalytic core
      domain (CCD) is described as well as its binding mode within the RNase H
      catalytic site to rationalize its selectivity. 

PMID- 25961959
TI  - Biodegradable CSMA/PECA/Graphene Porous Hybrid Scaffold for Cartilage Tissue
      Engineering.
AB  - Owing to the limited repair capacity of articular cartilage, it is essential to
      develop tissue-engineered cartilage for patients suffering from joint disease and
      trauma. Herein, we prepared a novel hybrid scaffold composed of methacrylated
      chondroitin sulfate (CSMA), poly(ethylene glycol) methyl ether-epsilon
      caprolactone-acryloyl chloride (MPEG-PCL-AC, PECA was used as abbreviation for
      MPEG-PCL-AC) and graphene oxide (GO) and evaluated its potential application in
      cartilage tissue engineering. To mimic the natural extracellular matrix (ECM) of
      cartilage, the scaffold had an adequate pore size, porosity, swelling ability,
      compression modulus and conductivity. Cartilage cells contacted with the scaffold
      remained viable and showed growth potential. Furthermore, CSMA/PECA/GO scaffold
      was biocompatible and had a favorable degradation rate. In the cartilage tissue
      repair of rabbit, Micro-CT and histology observation showed the group of
      CSMA/PECA/GO scaffold with cellular supplementation had better chondrocyte
      morphology, integration, continuous subchondral bone, and much thicker newly
      formed cartilage compared with scaffold group and control group. Our results show
      that the CSMA/PECA/GO hybrid porous scaffold can be applied in articular
      cartilage tissue engineering and may have great potential to in other types of
      tissue engineering applications. 

PMID- 25961962
TI  - Therapy Stratifications and Novel Approach in Pursuit of AIDS Related Kaposi's
      Sarcoma Management- A paradigm for Non Invasiveness.
AB  - Cancer in individuals suffering with HIV and AIDS has become a common source of
      morbidity and mortality, especially in the underdeveloped world in which Kaposi's
      sarcoma is the most occurring tumor of vascular endothelium frequently seen in
      patients suffering from AIDS. Suffering individuals are invariably co-infected
      with HIV and HHV-8 virus. The conventional modes for chemotherapies may be
      clinically useful in patients with Kaposi's sarcoma. Though advancements in
      treatment modalities of AIDS related Kaposi's sarcoma have been successfully
      achieved, till date an exclusive therapy of golden standard has not been
      principally defined that can deliver the drug via non-invasive route. Novel
      concepts of treatment primarily address the factors that are associated with the
      pathogenesis of critical disease. On the other hand local therapies are aimed at
      eradicating primary lesions; and systemic chemotherapies are aimed to treat
      widespread visceral involvement. Increased understanding of the mechanisms
      underlying viral tumorigenesis will hopefully portray new therapeutic strategies.
      This review discusses novel drug delivery strategies that have been investigated
      for the effective and safe management of AIDS related kaposi's sarcoma. The
      review also highlights, the lipid based ultradeformable vesicular system that
      offers attractive drug delivery platform capable of delivering its payload
      without using invasive technique. These systems offer advance models for
      efficacious treatment of the future therapy aiming Kaposi's sarcoma. 

PMID- 25961963
TI  - Electric Field-Controlled Ion Transport In TiO2 Nanochannel.
AB  - On the basis of biological ion channels, we constructed TiO2 membranes with rigid
      channels of 2.3 nm to mimic biomembranes with flexible channels; an external
      electric field was employed to regulate ion transport in the confined channels at
      a high ionic strength in the absence of electrical double layer overlap. Results
      show that transport rates for both Na+ and Mg2+ were decreased irrespective of
      the direction of the electric field. Furthermore, a voltage-gated selective ion
      channel was formed, the Mg2+ channel closed at -2 V, and a reversed relative
      electric field gradient was at the same order of the concentration gradient,
      whereas the Na+ with smaller Stokes radius and lower valence was less sensitive
      to the electric field and thus preferentially occupied and passed the channel.
      Thus, when an external electric field is applied, membranes with larger
      nanochannels have promising applications in selective separation of mixture salts
      at a high concentration.

PMID- 25961965
TI  - Electronic Cigarettes: Perhaps the Devil Unknown Is Better Than the Devil Known.

PMID- 25961964
TI  - Individual care plans for chronically ill patients within primary care in the
      Netherlands: Dissemination and associations with patient characteristics and
      patient-perceived quality of care.
AB  - OBJECTIVE: To examine the use of individual care plans (ICPs) within primary
      chronic illness care in the Netherlands, and to explore the relationships between
      ICP use, patient characteristics, and patient-perceived quality of care. DESIGN:
      Cross-sectional study using survey data from a panel of chronically ill patients
      and medical registration data provided by their general practices. SETTING AND
      SUBJECTS: A sample of 1377 patients with somatic chronic disease(s) randomly
      selected in general practices throughout the Netherlands, supplemented with a
      sample of 225 COPD patients, also recruited from general practices. MAIN OUTCOME
      MEASURES: (i) Percentage of ICP use based on self-report by chronically ill
      patients, and (ii) patient-perceived quality of care as assessed using the
      Patient Assessment of Chronic Illness Care (PACIC). RESULTS: ICP use among the
      total generic sample was low (9%), but slightly higher (13%) among patients
      diagnosed with diabetes or COPD, diseases for which disease management programmes
      have been set up in the Netherlands. Patients with a low educational level and
      patients with poor(er) self-rated health were more likely to have an ICP.
      Compared with patients without an ICP, patients with an ICP more often reported
      that the care they received was patient-centred, proactive, planned, and included
      collaborative goal setting, problem-solving, and follow-up support. CONCLUSION
      AND IMPLICATIONS: Findings reveal a discrepancy between practice and policy
      aspirations regarding ICP use in primary chronic illness care. More research is
      needed to gain insight into the effectiveness of ICPs to improve the quality of
      chronic illness care in various patient populations.

PMID- 25961966
TI  - Estrogen receptor-alpha: molecular mechanisms and interactions with the ubiquitin
      proteasome system.
AB  - Estrogen receptor-alpha (ERalpha) is a protein with a long history of study that
      precedes the advent of modern molecular biology. Over the course of 50 years,
      ERalpha has been increasingly recognized as a prominent model for the study of
      the mechanism of gene transcription in vertebrates. It also serves as a
      regulatory molecule for numerous physiological and disease states. Several
      fundamental insights have been made using ERalpha as a model protein, from the
      discovery that endocrine hormones elicit gene transcription to our understanding
      of the relationship between ERalpha-mediated transcription and transcription
      factor degradation by the ubiquitin proteasome system (UPS). Understanding of
      receptor protein degradation developed alongside other aspects of its molecular
      biology, from early observations in the 1960s that ERalpha is degraded on hormone
      treatment to the current understanding of ERalpha transcriptional regulation by
      the UPS. Here, we present the concept of ERalpha turnover from the perspective of
      the historical development of this notion and highlight some of the latest
      discoveries regarding this process. We discuss the logic and significance of
      ERalpha degradation pathways in the context of cell and whole-organism
      homeostasis. 

PMID- 25961967
TI  - A native steroid hormone derivative triggers the resolution of inflammation.
AB  - Inflamed tissues produce both prostaglandins (PGs) and 7alpha-hydroxylated
      derivatives of native circulating 3beta-hydroxysteroids. These 7alpha
      hydroxysteroids are in turn transformed into 7beta-hydroxylated epimers by 11beta
      hydroxysteroid dehydrogenase type 1 in the tissue. 7beta-Hydroxy-epiandrosterone
      (7beta-hydroxy-EpiA) affects PG production in two models of inflammation, dextran
      sodium sulfate-induced colitis in the rat and TNF-alpha-induced activation of PG
      production and PG synthase expression in cultured human peripheral blood
      monocytes (hPBMC). Treatment with 7beta-hydroxy-EpiA led to a shift from high to
      low colonic PGE2 levels and from low to high 15-deoxy-Delta12-14-PGJ2 (15d-PGJ2)
      levels, together with changes in the expression of the respective PG synthases
      and resolution of colonic inflammation. Addition of 7beta-hydroxy-EpiA to hPBMC
      also changed the expression of PG synthases and decreased PGE2 while increasing
      15d-PGJ2 production. These effects were only observed with 7beta-hydroxy-EpiA and
      not with 7alpha-hydroxy- or 7beta-hydroxy-dehydroepiandrosterone (7alpha-hydroxy
      DHEA and 7beta-hydroxy-DHEA). 15d-PGJ2, which is the native ligand for peroxisome
      proliferator-activated receptor subtype gamma, contributes to cell protection and
      to the resolution of inflammation. Our results therefore suggest that 7beta
      hydroxy-EpiA may facilitate inflammatory resolution by shifting PG production
      from PGE2 to PGD2 and 15d-PGJ2. The finding that 7beta-hydroxy-EpiA was effective
      at nM concentrations, whereas the two structurally closely related
      hydroxysteroids 7alpha-hydroxy-DHEA and 7beta-hydroxy-DHEA were inactive suggests
      that the effects of 7beta-hydroxy-EpiA are specific to this steroid and may be
      mediated by a specific receptor. 

PMID- 25961968
TI  - Therapeutic implications of brain steroidogenesis.
AB  - The nervous system is a steroidogenic tissue and several steroids synthesized
      locally in the brain, such as pregnenolone, progesterone and estradiol, modulate
      neuronal and glial physiology and are neuroprotective. The brain upregulates
      steroidogenesis at sites of injury as part of a program triggered by neural
      tissue to cope with neurodegenerative insults. Pharmacological targets to
      increase brain steroidogenesis and promote neuroprotection include the molecules
      that transport cholesterol to the inner mitochondrial membrane, where the first
      enzyme for steroidogenesis is located. Furthermore, the human gene encoding
      aromatase, the enzyme that synthesizes estradiol, is under the control of
      different tissue-specific promoters, and it is therefore conceivable that
      selective aromatase modulators can be developed that will enhance the expression
      of the enzyme and the consequent increase in estrogen formation in the brain but
      not in other tissues. 

PMID- 25961969
TI  - Beneficial effects of 2 years of administration of parenteral testosterone
      undecanoate on the metabolic syndrome and on non-alcoholic liver steatosis and C
      reactive protein.
AB  - BACKGROUND: Elderly men often show a concurrence of a decline of testosterone
      with attributes of the metabolic syndrome. This study tested the effects of
      normalization of testosterone. MATERIALS AND METHODS: A total of 122 hypogonadal
      men (18-83 years, mean 59.6+/-8.0 years; n=11<45 years, n=25<55 years, n=53<65
      years) were included in the study. Their baseline testosterone levels were
      between 0.14 and 4.51 ng/mL (n>4.90 ng/mL) and were treated with parenteral
      testosterone undecanoate for 2 years as the sole intervention (administration at
      0 and 6 weeks, and thereafter every 12 weeks). RESULTS: Plasma testosterone
      increased from 3.3+/-1.9 ng/mL to 4.1+/-1.5 ng/mL (p<0.01) at 3 months, and then
      stabilized at 6.8+/-1.3 ng/mL after the first 6 months. There was a remarkable
      progressive linear decline in body weight, body mass index, and waist
      circumference over the entire study period. Plasma cholesterol decreased
      significantly over the first 12 months, and then stabilized. Plasma glucose,
      triglycerides, low-density lipoprotein cholesterol, and C-reactive protein
      decreased significantly and high-density lipoprotein cholesterol increased
      significantly over the 24-month study period in a non-linear manner. There was a
      significant decrease in aspartate aminotransferase and alanine aminotransferase
      levels over the first 9 and 12 months, and then values leveled off. Changes in
      variables were largely correlated with changes in testosterone levels. At
      baseline, 47 out of 122 subjects fulfilled the metabolic syndrome criteria as
      defined by the National Cholesterol Education Program (2001); after 2 years of
      testosterone treatment, this number had declined to 11 out of 122 subjects.
      CONCLUSION: With testosterone treatment over 2 years, the most significant
      improvement of the metabolic syndrome was noted over the first 12 months, but
      over the following 12 months further improvement was also observed. With regard
      to safety of testosterone administration to mainly elderly men, a number of
      safety measures were carried out.

PMID- 25961971
TI  - Pharmacotherapy with 17beta-estradiol and progesterone prevents development of
      mouse experimental autoimmune encephalomyelitis.
AB  - BACKGROUND: Pregnant women with multiple sclerosis (MS) show disease remission in
      the third trimester concomitant with high circulating levels of sex steroids.
      Rodent experimental autoimmune encephalomyelitis (EAE) is an accepted model for
      MS. Previous studies have shown that monotherapy with estrogens or progesterone
      exert beneficial effects on EAE. The aim of the present study was to determine if
      estrogen and progesterone cotherapy of C57BL/6 female mice provided substantial
      protection from EAE. METHODS: A group of mice received single pellets of
      progesterone (100 mg) and 17 beta-estradiol (2.5 mg) subcutaneously 1 week before
      EAE induction, whereas another group were untreated before EAE induction. On day
      16 we compared the two EAE groups and control mice in terms of clinical scores,
      spinal cord demyelination, expression of myelin basic protein and proteolipid
      protein, macrophage cell infiltration, neuronal expression of brain-derived
      neurotrophic factor mRNA and protein, and the number of glial fribrillary acidic
      protein (GFAP)-immunopositive astrocytes. RESULTS: Clinical signs of EAE were
      substantially attenuated by estrogen and progesterone treatment. Steroid
      cotherapy prevented spinal cord demyelination, infiltration of inflammatory cells
      and GFAP+ astrogliocytes to a great extent. In motoneurons, expression of BDNF
      mRNA and protein was highly stimulated, indicating concomitant beneficial effects
      of the steroid on neuronal and glial cells. CONCLUSIONS: Cotherapy with estrogen
      and progesterone inhibits the development of major neurochemical abnormalities
      and clinical signs of EAE. We suggest that a combination of neuroprotective,
      promyelinating and immuno-suppressive mechanisms are involved in these beneficial
      effects.

PMID- 25961970
TI  - Effects of isoquinolonesulfonamides on action potential secretion coupling in
      pituitary cells.
AB  - BACKGROUND: Pituitary lactotrophs fire action potentials spontaneously and the
      associated voltage-gated calcium influx is sufficient to maintain high and steady
      prolactin release. Several intracellular proteins can mediate the action of
      calcium influx on prolactin secretion, including calmodulin-dependent protein
      kinases. Here, we studied effects of isoquinolonesulfonamides KN-62 and KN-93,
      calmodulin-dependent protein kinase inhibitors, and KN-92, an inactive analog, on
      spontaneous electrical activity, voltage-gated calcium influx, cyclic nucleotide
      production, and basal prolactin release. METHODS: The effects of these compounds
      on electrical activity and calcium signaling was measured in single lactotrophs
      and cyclic nucleotide production and prolactin release were determined in static
      culture and perifusion experiments of anterior pituitary cells from postpubertal
      female rats. RESULTS: KN-62 and KN-93 blocked basal prolactin release in a dose-
      and time-dependent manner, suggesting that calmodulin-dependent protein kinase
      could mediate the coupling of electrical activity and secretion. However, a
      similar effect on basal prolactin release was observed on application of KN-92,
      which does not inhibit this kinase. KN-93 also inhibited cAMP and cGMP
      production, but inhibition of prolactin release was independent of the status of
      cyclic nucleotide production. Single cell measurements revealed abolition of
      spontaneous and depolarization-induced electrical activity and calcium transients
      in KN-92/93-treated cells, with a time course comparable to that observed in
      secretory studies. CONCLUSIONS: The results suggest that caution should be used
      when interpreting data from studies using isoquinolonesulfonamides to evaluate
      the role of calmodulin-dependent protein kinases in excitable endocrine cells,
      because inactive compounds exhibit comparable effects on action potential
      secretion coupling to those of active compounds.

PMID- 25961972
TI  - Sequential transformation of 4-androstenedione into dihydrotestosterone in
      prostate carcinoma (DU-145) cells indicates that 4-androstenedione and not
      testosterone is the substrate of 5alpha-reductase.
AB  - BACKGROUND: Although it is well recognized that 5alpha-reductases possess higher
      affinity for 4-androstenedione than testosterone, and the affinity of 4
      androstenedione is higher for 5alpha-reductases than 17beta-hydroxysteroid
      dehydrogenases, it is generally believed that dihydrotestosterone is necessarily
      produced by the transformation of testosterone into dihydrotestosterone,
      suggesting that the step catalyzed by 17beta-hydroxysteroid dehydrogenase
      precedes the step catalyzed by 5alpha-reductase. This interpretation is in
      contradiction with the enzymatic kinetic law that suggests that the 5alpha
      reduction step that catalyzes the transformation of 4-dione into 5alpha
      androstane-3,17-dione precedes the 17keto-reduction step. MATERIALS AND METHODS:
      To verify which of these two pathways is operative, we quantified mRNA expression
      levels of steroidogenic enzymes in prostate carcinoma DU-145 cells by real-time
      PCR and determined the metabolites produced after incubation with [14C]4-dione in
      the presence and absence of a 5alpha-reductase inhibitor and analyzed the
      metabolites produced by thin layer chromatography and HPLC. RESULTS: Real-time
      PCR analysis strongly suggests that the new type 3 5alpha-reductase is
      responsible for 5alpha-reductase activity in DU-145 cells. Steroid profile
      analysis shows that in the absence of inhibitor 5alpha-androstanedione is first
      produced, followed by the production of androsterone and dihydrotestosterone. The
      concentration of testosterone was not detectable. In the presence of Finasteride,
      an inhibitor of 5alpha-reductase, there was no transformation of 4
      androstenedione and also there was no production of testosterone. The present
      data clearly indicate that the biosynthesis of dihydrotestosterone in DU-145
      cells does not require testosterone as intermediate, and the step catalyzed by
      5alpha-reductase precedes the step catalyzed by 17beta-hydroxysteroid
      dehydrogenase.

PMID- 25961973
TI  - Monitoring gene expression in muscle tissue of macaca fascicularis under the
      influence of testosterone and SARM.
AB  - The focus of this study was to evaluate data on the gene expression profiles
      induced by testosterone and a selective androgen receptor modulator (SARM, TAP
      Pharmaceutical Products Inc., Lake Forest, IL, USA) in androgen sensitive muscle
      tissue to obtain a better understanding on the molecular mechanisms of action and
      to identify biomarkers for SARM function in primate organs. A total of 24 male
      cyomolgus monkeys were divided into four groups: testosterone group, SARM1 group,
      SARM10 group, and control group, each consisting of six animals. The testosterone
      group was treated i.m. with 3.0 mg/kg Testostoviron(r)-depot-250 (Schering,
      Berlin, Germany) every 2 weeks, the SARM1 and SARM10 groups with 1 mg/kg or 10
      mg/kg SARM LGD2941 daily, and the control group was not treated. Muscle biopsies
      from musculus quadriceps and musculus triceps were collected at three time
      points: baseline time point before SARM application (control), on day 16, and on
      day 90 of treatment. A total of 30 candidate genes were selected according to
      their functionality by screening the actual literature and were composed to the
      following functional groups: cell cycle, endocrine factors, energy metabolism,
      muscle fiber proteins, muscle specific transcription factors, protein metabolism,
      and satellite cell biology. Biomarkers were identified as genes regulated from
      baseline in any of the three treatment groups at day 16 or day 90 using analysis
      of variance with baseline defined as the contrast group. Out of 23 tested
      candidate genes, 3 were significantly regulated in m. quadriceps after 90 days
      treatment; in m. triceps no significant differences were identified. Cathepsin L,
      calpain 3, and insulin like growth factor binding protein 3 could be identified
      as first biomarkers, and first physiological differences between control and
      treatment samples were determined. Both testosterone and SARM LGD2941 appear to
      have similar effects after 90 days treatment, and thus a longer-term therapy with
      these substances can be recommended. 

PMID- 25961974
TI  - Sex hormone-binding globulin in congenital adrenal hyperplasia.
AB  - BACKGROUND: Sex hormone-binding globulin biosynthesis is influenced by three
      hormonal systems: gonadal, insular and thyroid. Congenital adrenal hyperplasia is
      characterized by overproduction of adrenal androgens associated with impaired
      insulin sensitivity, hyperinsulinemia and often also with hypothyroidism. Only
      scarce data are available concerning congenital adrenal hyperplasia. The
      objective of this study was to determine the distribution of sex hormone-binding
      globulin and free testosterone levels in these patients and to what extent these
      values correlate with actual 17-hydroxyprogesterone and androstenedione levels,
      which are commonly used for monitoring of treatment effectiveness. MATERIALS AND
      METHODS: A total of 300 retrospective laboratory records of 78 males and boys and
      456 records of 162 girls and premenopausal women with diagnosis of congenital
      adrenal hyperplasia under common substitution treatment were evaluated
      statistically. The data were divided artificially into groups of low, normal and
      high levels, with respect to physiological concentrations for each sex and age.
      The percentages of the total in each group were calculated. RESULTS: Whereas an
      almost Gaussian distribution occurred for males, the data for females displayed a
      considerable shift to low sex hormone-binding globulin and accordingly high free
      testosterone levels. Sex hormone-binding globulin levels did not correlate with
      17-hydroxyprogesterone. CONCLUSION: Low sex hormone-binding globulin levels in
      congenital adrenal hyperplasia, at least in females, reflect their involvement in
      insular and eventually thyroid axes, rather than the effectiveness of
      substitution.

PMID- 25961975
TI  - The influence of low dose finasteride, a type II 5alpha-reductase inhibitor, on
      circulating neuroactive steroids.
AB  - BACKGROUND: Finasteride is a 5alpha-reductase inhibitor that has received
      clinical approval for the treatment of human benign prostatic hyperplasia and
      androgenetic alopecia. The treatment is practically without side effects,
      although some occasional cases of depression syndrome have been reported. 5alpha
      Reductase is an enzyme responsible for the reduction of testosterone,
      progesterone or deoxycorticosterone to their 5alpha-reduced derivatives
      possessing anticonvulsant, antidepressant, and anxiolytic activity. Therefore,
      the formation of GABAergic neuroactive steroids is likely to be impacted by
      finasteride. OBJECTIVE: The objective of the study was to show how the treatment
      of premature androgenetic alopecia with low doses (1 mg/day) of finasteride
      influences the broad spectrum of steroids with potential neuroactivity. METHODS:
      A group of 12 men with premature androgenetic alopecia participated in the
      present study. The steroid hormone profile was determined for all individuals.
      Finasteride was administered for 4 months at a daily dose of 1 mg. After the
      treatment, the same hormonal profile was determined again. RESULTS: 5alpha
      Reduced steroids, e.g., 5alpha-dihydrotestosterone, androsterone,
      epiandrosterone, 5alpha-androstene-3alpha,17beta-diol, allopregnanolone,
      isopregnaolone, and some 5-ene steroids, such as dehydroepiandrosterone and
      pregnenolone, decreased gradually during treatment. CONCLUSIONS: The decrease of
      5alpha-reduced steroids, especially of allopregnanediol, dihydrotestosterone, and
      pregnenolone, is probably one of the factors responsible for the increased
      occurrence of depression in men treated with finasteride, even at low doses.

PMID- 25961976
TI  - The use of peptide analogs for the treatment of gastrointestinal, pancreatic,
      liver and urinary bladder cancers.
AB  - Peptide hormones can influence the development and growth of many cancers which
      are not considered classical hormone-dependent tumors. Analogs of somatostatin,
      bombesin/gastrin-releasing peptide (GRP), luteinizing hormone-releasing hormone
      (LH-RH) and growth hormone-releasing hormone (GH-RH) can interfere with receptors
      on tumor cells or intracellular pathways that are important in cell proliferation
      and in this way inhibit tumor growth. The first part of this review explains how
      these peptide hormones and their analogs affect tumors. The second part of this
      review describes how various hormone analogs can be used for the treatment of
      gastric, colorectal, pancreatic, liver and urinary bladder cancers. These tumors
      are major health problems worldwide and their treatment remains a great
      challenge. Receptors for somatostatin, bombesin/GRP, LH-RH and GH-RH are present
      in a large percentage of these cancers. We have developed a series of cytotoxic
      peptides based on doxorubicin or its derivative 2-pyrrolino-doxorubicin coupled
      to an analog of LH-RH, somatostatin or bombesin. This new class of targeted
      analogs might provide a more effective therapy for various cancers that express
      receptors for these carrier peptides, while producing significantly reduced
      peripheral toxicity. Under experimental conditions, these peptide hormone analogs
      strongly inhibited the growth of these tumors. Cytotoxic analogs were
      particularly effective on tumors that express the specific peptide receptors and
      acted more powerfully than the carrier peptide or the cytotoxic compound alone.
      Clinical trials on these peptide analogs are in progress. 

PMID- 25961977
TI  - Are estradiol metabolites involved in gynaecological carcinogenesis?
AB  - Certain estradiol metabolites are biologically active, sometimes several times
      more potent than their parent substance. Highly sophisticated laboratory methods
      allow us to understand oestrogenic effects as a net effect of the corresponding
      metabolite pattern. Currently, research is focused on the anticancerogenic
      effects of 2-hydroxyestrone and particularly 2-methoxyestradiol, as well as the
      possible carcinogenic properties of 4-hydroxyoestrogens and 16alpha
      hydroxyestrone. The clinical relevance of these activities, demonstrated in in
      vitro and animal experiments, remains unclear - it is proven, however, that the
      metabolite production can be altered in certain malignancies such as endometrial
      , breast- and cervical carcinoma. Clinical studies, including our studies, have
      demonstrated a negative correlation between the ratio of 2-hydroxyestrone to
      16alpha-hydroxyestrone and breast cancer risk. However, the design and
      interpretation of such studies should consider factors influencing metabolic
      pattern such as diet, physical activity, smoking, as well as internal diseases
      and certain drugs. 

PMID- 25961978
TI  - Inhibition of aromatase activity in MCF-7aro human breast cancer cells by the
      natural androgens testosterone and androstenedione.
AB  - BACKGROUND: The human breast contains all the enzymes responsible for local
      bioformation of estradiol (E2). Two principal pathways are implicated in the last
      steps of E2 formation: the 'aromatase' which transforms androgens into estrogens,
      and the 'sulfatase' which converts estrogen sulfates into active unconjugated
      estrogens; activities found in both normal and cancerous breast. Aromatase
      inhibition by anti-aromatase agents is largely used with very positive results in
      the treatment of breast cancer patients. In this study, the effects of the
      natural androgens androstenedione and testosterone were explored on aromatase
      activity in a stable aromatase-expressing estrogen receptor-positive human breast
      cancer cell line MCF-7aro. MATERIALS AND METHODS: The cells were incubated with
      physiological concentrations of [3H]-testosterone (5 nmol/L) alone or in the
      presence of either testosterone or androstenedione (0.5 and 50 MUmol/L) 24 h at
      37 degrees C. Cellular radioactivity uptake was determined. [3H]-E2 was
      characterized by thin-layer chromatography. RESULTS: The MCF-7aro cells have a
      very high aromatase activity because conversion of [3H]-testosterone to [3H]-E2
      was 3.02+/-0.17 pmol/mg DNA in non-treated cells. Testosterone, at concentrations
      of 0.5 and 50 MUmol/L, provoked inhibition of E2 formation of 36% and 79%,
      respectively. The effect of androstenedione at 0.5 and 50 MUmol/L was 56% and
      76%, respectively. CONCLUSION: In breast cancer cells, the natural androgens
      testosterone and androstenedione, have the capacity to control bioformation of
      estradiol by blocking aromatase activity. The data can provide important
      information on the control mechanism of estrogen intratumoral levels and open new
      possibilities in breast cancer treatment.

PMID- 25961979
TI  - Editorial.

PMID- 25961980
TI  - Editorial.

PMID- 25961981
TI  - Brain glutaminases.
AB  - Glutaminase is considered as the main glutamate producer enzyme in brain.
      Consequently, the enzyme is essential for both glutamatergic and gabaergic
      transmissions. Glutamine-derived glutamate and ammonia, the products of
      glutaminase reaction, fulfill crucial roles in energy metabolism and in the
      biosynthesis of basic metabolites, such as GABA, proteins and glutathione.
      However, glutamate and ammonia are also hazardous compounds and danger lurks in
      their generation beyond normal physiological thresholds; hence, glutaminase
      activity must be carefully regulated in the mammalian brain. The differential
      distribution and regulation of glutaminase are key factors to modulate the
      metabolism of glutamate and glutamine in brain. The discovery of novel
      isoenzymes, protein interacting partners and subcellular localizations indicate
      new functions for brain glutaminase. In this short review, we summarize recent
      findings that point consistently towards glutaminase as a multifaceted protein
      able to perform different tasks. Finally, we will highlight the involvement of
      glutaminase in pathological states and its consideration as a potential
      therapeutic target. 

PMID- 25961982
TI  - The epigenetic regulation of autonomous replicons.
AB  - The discovery of autonomous replicating sequences (ARSs) in Saccharomyces
      cerevisiae in 1979 was considered a milestone in unraveling the regulation of
      replication in eukaryotic cells. However, shortly afterwards it became obvious
      that in Saccharomyces pombe and all other higher organisms ARSs were not
      sufficient to initiate independent replication. Understanding the mechanisms of
      replication is a major challenge in modern cell biology and is also a
      prerequisite to developing application-oriented autonomous replicons for gene
      therapeutic treatments. This review will focus on the development of non-viral
      episomal vectors, their use in gene therapeutic applications and our current
      knowledge about their epigenetic regulation. 

PMID- 25961983
TI  - Structure and molecular evolution of multicopper blue proteins.
AB  - The multicopper blue protein family, which contains cupredoxin-like domains as a
      structural unit, is one of the most diverse groups of proteins. This protein
      family is divided into two functionally different types of enzymes: multicopper
      oxidase and nitrite reductase. Multicopper oxidase catalyzes the oxidation of the
      substrate and then reduces dioxygen. The structures of many multicopper oxidases
      are already known, and until recently they were classified into two main groups:
      the three- and six-domain types. Both function as monomers and have three
      spectroscopically different copper sites: Types I (blue), II, and III (tri
      nuclear). Nitrite reductase is a closely related protein that contains Types I
      and II (mono-nuclear) coppers but reduces nitrite instead of dioxygen. Nitrite
      reductase, which consists of two domains, forms a homotrimer. Multicopper oxidase
      and nitrite reductase share similar structural architectures and also contain
      Type I copper. Therefore, it is proposed that they have a common ancestor
      protein. Recently, some two-domain type multicopper oxidases have been found and
      their crystal structures have been determined. They have a trimeric quaternary
      structure and contain an active site at the molecular interface such as nitrite
      reductase. These results support previous hypotheses and provide an insight into
      the molecular evolution of multicopper blue proteins. 

PMID- 25961984
TI  - Membrane progestin receptors: beyond the controversy, can we move forward?
AB  - Steroids are well-known mediators of many different physiological functions.
      Their best characterized mechanism of action involves interaction with well
      defined nuclear receptors and regulation of gene transcription. However, rapid
      effects of steroids have been reported which are incompatible with their
      classical long-term/slow effects. Although the concept of membrane-bound
      receptors for steroids which can transduce their rapid effects has been proposed
      many years ago, it is only recently that such proteins have been identified and
      characterized. In this review, we will discuss recent data regarding the rapid
      action of progesterone mediated by newly characterized membrane-bound receptors
      belonging to the progestin and adiponectin receptor family. 

PMID- 25961985
TI  - Epigenetic regulation of p16Ink4a and Arf by JDP2 in cellular senescence.
AB  - In response to accumulating cellular stress, cells protect themselves from
      abnormal growth by entering the senescent stage. Senescence is controlled mainly
      by gene products from the p16Ink4a/Arf locus. In mouse cells, the expression of
      p16Ink4a and Arf increases continuously during proliferation in cell culture.
      Transcription from the locus is under complex control. p16Ink4a and Arf respond
      independently to positive and negative signals, and the entire locus is
      epigenetically suppressed by histone methylation that depends on the Polycomb
      repressive complex-1 and -2 (PRC1 and PRC2). In fact, the PRCs associate with the
      p16Ink4a/Arf locus in young proliferating cells and dissociate in aged senescent
      cells. Thus, it seems that chromatin-remodeling factors that regulate association
      and dissociation of PRCs might be important players in the senescence program.
      Here, we summarize the molecular mechanisms that mediate cellular aging and
      introduce the Jun dimerization protein 2 (JDP2) as a factor that regulates
      replicative senescence by mediating dissociation of PRCs from the p16Ink4a/Arf
      locus. 

PMID- 25961986
TI  - The Musashi family RNA-binding proteins in stem cells.
AB  - The Musashi family is an evolutionarily conserved group of RNA-binding proteins.
      In mammal, two members of the group, Msi1 and Msi2, have been identified to date.
      Msi1 is considered to play roles in maintaining the stem cell status (stemness)
      of neural stem/progenitor cells in adults and in the development of central
      nervous system through translational regulation of its target mRNAs, which encode
      regulators of signal transduction and the cell cycle. Recently, strong expression
      of Msi1 in various somatic stem/progenitor cells of adult tissues, such as eye,
      gut, stomach, breast, and hair follicle, has been reported. The protein is also
      expressed in various cancer cells, and ectopically emerging cells have been found
      in neural tissues of patients with diseases involving neural disorder, including
      epilepsy. Many novel target mRNAs and regulatory pathways of Msi1 have been
      reported in recent years. Here, we present a review of the functions and action
      mechanisms of Msi1 protein and discuss possible directions for further study. 

PMID- 25961987
TI  - Ubiquitin fragments: their known biological activities and putative roles.
AB  - Ubiquitin (Ub) is involved in many key processes of cell biology. Identification
      of compounds that could interfere in the ubiquitination process is of importance.
      It could be expected that peptides derived from the Ub-binding regions might be
      able to interact with Ub receptors themselves and modify an ability of the Ub
      receptors interactions. This review summarizes current knowledge about known Ub
      derived peptides and discusses putative activity of unexplored Ub fragments.
      Among identified biologically active Ub-derived peptides, its decapeptide
      fragment of the LEDGRTLSDY sequence was found to exhibit strong immunosuppressive
      effects on the cellular and humoral immune responses, comparable to that of
      cyclosporine. Some of the Ub fragments possess strong antibacterial and
      antifungal potency. In the search for new peptides that could interfere in the
      interaction of Ub with other proteins, we investigated the pentapeptide Ub
      sequences present in non-ubiquitin proteins. Based on examination of the Swiss
      Prot database, we postulated that sequences of some Ub fragments often exist in
      other protein molecules. However, some of those motives are represented more
      frequently than others and could be involved in regulation of cellular processes
      related to Ub. 

PMID- 25961988
TI  - Recent progress in the field of neoglycoconjugate chemistry.
AB  - Glycosylation is probably the most complex secondary gene event that affects the
      vast majority of proteins in nature resulting in the occurrence of a
      heterogeneous mixture of glycoforms for a single protein. Many functions are
      exerted by single monosaccharides, well-defined oligosaccharides, or larger
      glycans present in these glycoproteins. To unravel these functions it is of the
      utmost importance to prepare well-defined single glycans conjugated to the
      underlying aglycon. In this review, the most recent developments are described to
      address the preparation of carbohydrate-amino acid (glyco-conjugates). Naturally
      occurring N- and O-linked glycosylation are described and the preparation of non
      natural sugar-amino acid linkages are also included. 

PMID- 25961989
TI  - Advances in research on the accumulation, redox behavior, and function of
      vanadium in ascidians.
AB  - The discovery of high levels of vanadium-containing compounds in ascidian blood
      cells goes back to 1911. Ascidians, which are also known as tunicates or sea
      squirts, belong to a subphylum of the Chordata, between the vertebrates and
      invertebrates. This discovery attracted the attention of an interdisciplinary
      group of chemists, physiologists, and biochemists, in part because of interest in
      the possible role of vanadium in oxygen transport as a prosthetic group in
      respiratory pigments, which was later shown not to be such a role, and in part
      because of the fact that high levels of vanadium were unknown in other organisms.
      The intracellular concentration of vanadium in some ascidian species can be as
      high as 350 mm, which is 107 times that in seawater. Vanadium ions, which are
      thought to be present in the +5 oxidation state in seawater, are reduced to the
      +3 oxidation state via the +4 oxidation state and are stored in the vacuoles of
      vanadium-containing cells called vanadocytes, where high levels of protons and
      sulfate ions are also found. Recently, many proteins and genes that might be
      involved in the accumulation and reduction of vanadium have been isolated. In
      this review, we not only trace the history of vanadium research but also describe
      recent advances in our understanding of the field from several viewpoints: (i)
      vanadium-accumulating blood cells, (ii) the energetics of vanadium accumulation,
      (iii) the redox mechanism of vanadium, (iv) the possible role of sulfate, and (v)
      the physiological roles of vanadium. 

PMID- 25961990
TI  - Cell penetrating peptides can exert biological activity: a review.
AB  - Cell penetrating peptides (CPPs) have been successful in delivering cargo into
      many different cell types and are an important alternative to other methods of
      permeation that might damage the integrity of the cell membrane. The traditional
      view of CPPs is that they are inert molecules that can be successfully used to
      deliver many cargos intracellularly. The goal of this review is to challenge this
      traditional understanding of CPPs. Recent literature has demonstrated that CPPs
      themselves can convey biological activity, including the alteration of gene
      expression and inhibition of protein kinases and proteolytic activity. Further
      characterization of CPPs is required to determine the extent of this activity.
      Research into the use of CPPs for intracellular delivery should continue with
      investigators being aware of these recent results. 

PMID- 25961991
TI  - Molecular bases of neuroserpin function and pathology.
AB  - Serpins build a large and evolutionary widespread protein superfamily, hosting
      members that are mainly Ser-protease inhibitors. Typically, serpins display a
      conserved core domain composed of three main beta-sheets and 9-10 alpha-helices,
      for a total of approximately 350 amino acids. Neuroserpin (NS) is mostly
      expressed in neurons and in the central and peripheral nervous systems, where it
      targets tissue-type plasminogen activator. NS activity is relevant for
      axogenesis, synaptogenesis and synaptic plasticity. Five (single amino acid) NS
      mutations are associated with severe neurodegenerative disease in man, leading to
      early onset dementia, epilepsy and neuronal death. The functional aspects of NS
      protease inhibition are linked to the presence of a long exposed loop (reactive
      center loop, RCL) that acts as bait for the incoming partner protease. Large NS
      conformational changes, associated with the cleavage of the RCL, trap the
      protease in an acyl-enzyme complex. Contrary to other serpins, this complex has a
      half-life of approximately 10 min. Conformational flexibility is held to be at
      the bases of NS polymerization leading to Collins bodies intracellular deposition
      and neuronal damage in the pathological NS variants. Two main general mechanisms
      of serpin polymerization are currently discussed. Both models require the
      swapping of the RCL among neighboring serpin molecules. Specific differences in
      the size of swapped regions, as well as differences in the folding stage at which
      polymerization can occur, distinguish the two models. The results provided by
      recent crystallographic and biophysical studies allow rationalization of the
      functional and pathological roles played by NS based on the analysis of four
      three-dimensional structures. 

PMID- 25961992
TI  - Tau and neurodegenerative disorders.
AB  - The mechanisms that render tau a toxic agent are still unclear, although
      increasing evidence supports the assertion that alterations of tau can directly
      cause neuronal degeneration. In addition, it is unclear whether neurodegeneration
      in various tauopathies occurs via a common mechanism or that specific differences
      exist. The aim of this review is to provide an overview of tauopathies from bench
      to bedside. The review begins with clinicopathological findings of familial and
      sporadic tauopathies. It includes a discussion of the similarities and
      differences between these two conditions. The second part concentrates on
      biochemical alterations of tau such as phosphorylation, truncation and
      acetylation. Although pathological phosphorylation of tau has been studied for
      many years, recently researchers have focused on the physiological role of tau
      during development. Finally, the review contains a summary of the significance of
      tauopathy model mice for research on neurofibrillary tangles, axonopathies, and
      synaptic alteration. 

PMID- 25961993
TI  - Aurora kinases orchestrate mitosis; who are the players?
AB  - The Aurora are a conserved family of serine/threonine kinases with essential
      functions in cell division. In mitosis, Aurora kinases are required for
      chromosome segregation, condensation and orientation in the metaphase plate,
      spindle assembly, and the completion of cytokinesis. This review presents the
      Aurora kinases, their partners and how their interactions impact on the different
      mitotic functions. 

PMID- 25961994
TI  - The chromosome peripheral proteins play an active role in chromosome dynamics.
AB  - The chromosome periphery is a chromosomal structure that covers the surface of
      mitotic chromosomes. The structure and function of the chromosome periphery has
      been poorly understood since its first description in 1882. It has, however, been
      proposed to be an insulator or barrier to protect chromosomes from subcellular
      substances and to act as a carrier of nuclear and nucleolar components to direct
      their equal distribution to daughter cells because most chromosome peripheral
      proteins (CPPs) are derived from the nucleolus or nucleus. Until now, more than
      30 CPPs were identified in mammalians. Recent immunostaining analyses of CPPs
      have revealed that the chromosome periphery covers the centromeric region of
      mitotic chromosomes in addition to telomeres and regions between two sister
      chromatids. Knockdown analyses of CPPs using RNAi have revealed functions in
      chromosome dynamics, including cohesion of sister chromatids, kinetochore
      microtubule attachments, spindle assembly and chromosome segregation. Because
      most CPPs are involved in various subcellular events in the nucleolus or nuclear
      at interphase, a temporal and spatial-specific knockdown method of CPPs in the
      chromosome periphery will be useful to understand the function of chromosome
      periphery in cell division. 

PMID- 25961995
TI  - Lipoprotein assembly and function in an evolutionary perspective.
AB  - Circulatory fat transport in animals relies on members of the large lipid
      transfer protein (LLTP) superfamily, including mammalian apolipoprotein B (apoB)
      and insect apolipophorin II/I (apoLp-II/I). ApoB and apoLp-II/I, constituting the
      structural (non-exchangeable) basis for the assembly of various lipoproteins,
      acquire lipids through microsomal triglyceride-transfer protein, another LLTP
      family member, and bind them by means of amphipathic alpha-helical and beta-sheet
      structural motifs. Comparative research reveals that LLTPs evolved from the
      earliest animals and highlights the structural adaptations in these lipid-binding
      proteins. Thus, in contrast to apoB, apoLp-II/I is cleaved post-translationally
      by a furin, resulting in the appearance of two non-exchangeable apolipoproteins
      in the single circulatory lipoprotein in insects, high-density lipophorin (HDLp).
      The remarkable structural similarities between mammalian and insect lipoproteins
      notwithstanding important functional differences relate to the mechanism of lipid
      delivery. Whereas in mammals, partial delipidation of apoB-containing
      lipoproteins eventually results in endocytic uptake of their remnants, mediated
      by members of the low-density lipoprotein receptor (LDLR) family, and degradation
      in lysosomes, insect HDLp functions as a reusable lipid shuttle capable of
      alternate unloading and reloading of lipid. Also, during muscular efforts (flight
      activity), an HDLp-based lipoprotein shuttle provides for the transport of lipid
      for energy generation. Although a lipophorin receptor - a homolog of LDLR - was
      identified that mediates endocytic uptake of HDLp during specific developmental
      periods, the endocytosed lipoprotein appears to be recycled in a transferrin-like
      manner. These data highlight that the functional adaptations in the lipoprotein
      lipid carriers in mammals and insects also emerge with regard to the functioning
      of their cognate receptors. 

PMID- 25961996
TI  - Variable contribution of protein kinases to the generation of the human
      phosphoproteome: a global weblogo analysis.
AB  - In an attempt to evaluate the contribution of individual protein kinases to the
      generation of the human phosphoproteome, we performed a global weblogo analysis
      exploiting a database of 45641 phosphosites (80% pSer, 11% pTyr, 9% pThr). The
      outcome of this analysis was then interpreted by comparison with similar logos
      constructed from bona fide phospoacceptor sites of individual pleiotropic
      kinases. The main conclusions that were drawn are as follows: (i) the hallmarks
      surrounding phosphorylated Ser/Thr residues are more pronounced than and sharply
      different from those found around phosphorylated Tyr, which is consistent with
      the view that local consensus sequences are particularly important for substrate
      recognition by Ser/Thr protein kinases. (ii) Only six residues are positively
      selected around phosphorylated Ser/Thr residues, notably Pro (particularly at
      n+1), Glu, and to a lesser extent Asp, at various positions with special
      reference to n+3, Arg (and to a much lesser extent Lys), particularly at n-3 and
      n-5, and Ser, at various positions, particularly n+4 and n-4. (iii) This
      composite signature reflects the contribution of kinases whose bona fide
      substrates exhibit logos partially overlapping that of the whole phosphoproteome.
      These are Pro-directed kinases belonging to the CMGC group, some basophilic
      kinases belonging to the ACG and CAMK groups, phosphate-directed kinases such as
      GSK3 and members of the CK1 group and the individual highly acidophilic CK2.
      Collectively taken our data support the concept that a relatively small number of
      highly pleiotropic kinases contribute to the generation of the great majority of
      the human Ser/Thr phosphoproteome. 

PMID- 25961997
TI  - Seven essential questions on G-quadruplexes.
AB  - The helical duplex architecture of DNA was discovered by Francis Crick and James
      Watson in 1951 and is well known and understood. However, nucleic acids can also
      adopt alternative structural conformations that are less familiar, although no
      less biologically relevant, such as the G-quadruplex. G-quadruplexes continue to
      be the subject of a rapidly expanding area of research, owing to their
      significant potential as therapeutic targets and their unique biophysical
      properties. This review begins by focusing on G-quadruplex structure, elucidating
      the intermolecular and intramolecular interactions underlying its formation and
      highlighting several substructural variants. A variety of methods used to
      characterize these structures are also outlined. The current state of G
      quadruplex research is then addressed by proffering seven pertinent questions for
      discussion. This review concludes with an overview of possible directions for
      future research trajectories in this exciting and relevant field. 

PMID- 25961998
TI  - MTERF factors: a multifunction protein family.
AB  - The MTERF family is a large protein family, identified in metazoans and plants,
      which consists of four subfamilies, MTERF1, 2, 3 and 4. Mitochondrial
      localisation was predicted for the vast majority of MTERF family members and
      demonstrated for the characterised MTERF proteins. The main structural feature of
      MTERF proteins is the presence of a modular architecture, based on repetitions of
      a 30-residue module, the mTERF motif, containing leucine zipper-like heptads. The
      MTERF family includes transcription termination factors: human mTERF, sea urchin
      mtDBP and Drosophila DmTTF. In addition to terminating transcription, they are
      involved in transcription initiation and in the control of mtDNA replication.
      This multiplicity of functions seems to flank differences in the gene
      organisation of mitochondrial genomes. MTERF2 and MTERF3 play antithetical roles
      in controlling mitochondrial transcription: that is, mammalian and Drosophila
      MTERF3 act as negative regulators, whereas mammalian MTERF2 functions as a
      positive regulator. Both proteins contact mtDNA in the promoter region, perhaps
      establishing interactions, either mutual or with other factors. Regulation of
      MTERF gene expression in human and Drosophila depends on nuclear transcription
      factors NRF-2 and DREF, respectively, and proceeds through pathways which appear
      to discriminate between factors positively or negatively acting in mitochondrial
      transcription. In this emerging scenario, it appears that MTERF proteins act to
      coordinate mitochondrial transcription. 

PMID- 25961999
TI  - Chromatin regulators: weaving epigenetic nets.
AB  - In multicellular organisms differentiated cells must maintain their cellular
      memory, which will be faithfully inherited and maintained by their progeny. In
      addition, these specialized cells are exposed to specific environmental and cell
      intrinsic signals and will have to appropriately respond to them. Some of these
      stimuli lead to changes in a subset of genes or to a genome-wide reprogramming of
      the cells that will remain after stimuli removal and, in some instances, will be
      inherited by the daughter cells. The molecular substrate that integrates cellular
      memory and plasticity is the chromatin, a complex of DNA and histones unique to
      eukaryotes. The nucleosome is the fundamental unit of the chromatin and
      nucleosomal organization defines different chromatin conformations. Chromatin
      regulators affect chromatin conformation and accessibility by covalently
      modifying the DNA or the histones, substituting histone variants, remodeling the
      nucleosome position or modulating chromatin looping and folding. These regulators
      frequently act in multiprotein complexes and highly specific interplays among
      chromatin marks and different chromatin regulators allow a remarkable array of
      possibilities. Therefore, chromatin regulator nets act to propagate the
      conformation of different chromatin regions through DNA replication and mitosis,
      and to remodel the chromatin fiber to regulate the accessibility of the DNA to
      transcription factors and to the transcription and repair machineries. Here, the
      state-of-the-art of the best-known chromatin regulators is reviewed. 

PMID- 25962000
TI  - Epigenetic drugs for cancer treatment and prevention: mechanisms of action.
AB  - This review provides a brief overview of the basic principles of epigenetic gene
      regulation and then focuses on recent development of epigenetic drugs for cancer
      treatment and prevention with an emphasis on the molecular mechanisms of action.
      The approved epigenetic drugs are either inhibitors of DNA methyltransferases or
      histone deacetylases (HDACs). Future epigenetic drugs could include inhibitors
      for histone methyltransferases and histone demethylases and other epigenetic
      enzymes. Epigenetic drugs often function in two separate yet interrelated ways.
      First, as epigenetic drugs per se, they modulate the epigenomes of premalignant
      and malignant cells to reverse deregulated epigenetic mechanisms, leading to an
      effective therapeutic strategy (epigenetic therapy). Second, HDACs and other
      epigenetic enzymes also target non-histone proteins that have regulatory roles in
      cell proliferation, migration and cell death. Through these processes, these
      drugs induce cancer cell growth arrest, cell differentiation, inhibition of tumor
      angiogenesis, or cell death via apoptosis, necrosis, autophagy or mitotic
      catastrophe (chemotherapy). As they modulate genes which lead to enhanced
      chemosensitivity, immunogenicity or dampened innate antiviral response of cancer
      cells, epigenetic drugs often show better efficacy when combined with
      chemotherapy, immunotherapy or oncolytic virotherapy. In chemoprevention, dietary
      phytochemicals such as epigallocatechin-3-gallate and sulforaphane act as
      epigenetic agents and show efficacy by targeting both cancer cells and the tumor
      microenvironment. Further understanding of how epigenetic mechanisms function in
      carcinogenesis and cancer progression as well as in normal physiology will enable
      us to establish a new paradigm for intelligent drug design in the treatment and
      prevention of cancer. 

PMID- 25962001
TI  - Epigenetic regulation of protein glycosylation.
AB  - Protein N-glycosylation is an ancient metabolic pathway that still exists in all
      three domains of life (Archaea, Bacteria and Eukarya). The covalent addition of
      one or more complex oligosaccharides (glycans) to protein backbones greatly
      diversifies their structures and makes the glycoproteome several orders of
      magnitude more complex than the proteome itself. Contrary to polypeptides, which
      are defined by a sequence of nucleotides in the corresponding genes, the glycan
      part of glycoproteins are encoded in a complex dynamic network of hundreds of
      proteins, whereby activity is defined by both genetic sequence and the regulation
      of gene expression. Owing to the complex nature of their biosynthesis, glycans
      are particularly versatile and apparently a large part of human variation derives
      from differences in protein glycosylation. Composition of the individual glycome
      appears to be rather stable, and thus differences in the pattern of glycan
      synthesis between individuals could originate either from genetic polymorphisms
      or from stable epigenetic regulation of gene expression in different individuals.
      Studies of epigenetic modification of genes involved in protein glycosylation are
      still scarce, but their results indicate that this process might be very
      important for the regulation of protein glycosylation. 

PMID- 25962002
TI  - Bacterial cleanup: lateral diffusion of hydrophobic molecules through protein
      channel walls.
AB  - The outer membrane (OM) of Gram-negative bacteria forms a very efficient barrier
      against the permeation of both hydrophilic and hydrophobic compounds, owing to
      the presence of lipopolysaccharides on the outside of the cell. Although much is
      known about the OM passage of hydrophilic molecules, it is much less clear how
      hydrophobic molecules cross this barrier. Members of the FadL channel family,
      which are widespread in Gram-negative bacteria, are so far the only proteins with
      an established role in the uptake of hydrophobic molecules across the OM. Recent
      structural and biochemical research has shown that these channels operate
      according to a unique lateral diffusion mechanism, in which the substrate moves
      from the lumen of the barrel into the OM via an unusual opening in the wall of
      the barrel. Understanding how hydrophobic molecules cross the OM is not only of
      fundamental importance but could also have applications in the design of novel,
      hydrophobic drugs, biofuel production and the generation of more efficient
      bacterial biodegrader strains. 

PMID- 25962003
TI  - RNA duplexes in transcriptional regulation.
AB  - Transcriptional regulation by small RNA molecules, including small interfering
      RNA and microRNA, has emerged as an important gene expression modulator. The
      regulatory pathways controlling gene expression, post-transcriptional gene
      silencing and transcriptional gene silencing (TGS) have been demonstrated in
      yeast, plants and more recently in human cells. In this review, we discuss the
      currents models of transcriptional regulation and the main components of the RNA
      induced silencing complex and RNA-induced transcriptional silencing complex
      machinery, as well as confounding off-target effects and gene activation. We also
      discuss RNA-mediated TGS within the NF-kappaB motif of the human immunodeficiency
      virus type 1 5' long tandem repeat promoter region and the associated epigenetic
      modifications. Finally, we outline the current RNA interference (RNAi) delivery
      methods and describe the current status of human trials investigating potential
      RNAi therapeutics for several human diseases. 

PMID- 25962004
TI  - Secreted bone morphogenetic protein antagonists of the Chordin family.
AB  - Chordin, Chordin-like 1, and Chordin-like 2 are secreted bone morphogenetic
      protein (BMP) antagonists with highly conserved Chordin-like cysteine-rich
      domains. Recently, Brorin and Brorin-like have been identified as new Chordin
      like BMP antagonists. A Chordin ortholog, Short gastrulation, has been identified
      in Drosophila, a protostome, but not other orthologs. By contrast, Chordin,
      Chordin-like 1, and Chordin-like 2 have been identified in Ciona intestinalis,
      the closest living relatives of the vertebrates, but Brorin and Brorin-like have
      not. However, all these genes have been identified in most vertebrates. These
      results indicate that Chordin, Chordin-like 1, and Chordin-like 2 were generated
      early in the metazoan lineage. Later on, Brorin and Brorin-like were potentially
      generated by a genome duplication event in early vertebrate evolution. All four
      cysteine-rich domains of Chordin are essential for the regulation of its action.
      However, Chordin-like 1, Chordin-like 2, Brorin, and Brorin-like contain only two
      or three cysteine-rich domains. Although their mechanisms of action remain
      unclear, they might be distinct from that of Chordin. The expression profiles of
      these genes in mice and zebrafish indicate unique roles at embryonic and
      postnatal stages. Mutant/knockdown mouse and zebrafish phenotypes indicate roles
      in morphogenesis during gastrulation, dorsoventral axis formation, ear,
      pharyngeal, and neural development, and venous and arterial patterning. Aberrant
      Chordin expression might result in hereditary diseases and cancer. In addition,
      altered serum Chordin and Chordin-like 1 levels are also observed in non
      hereditary diseases. Together, these results indicate pathophysiological roles. 

PMID- 25962005
TI  - Propeptides as modulators of functional activity of proteases.
AB  - Most proteases are synthesized in the cell as precursor-containing propeptides.
      These structural elements can determine the folding of the cognate protein,
      function as an inhibitor/activator peptide, mediate enzyme sorting, and mediate
      the protease interaction with other molecules and supramolecular structures. The
      data presented in this review demonstrate modulatory activity of propeptides
      irrespective of the specific mechanism of action. Changes in propeptide
      structure, sometimes minor, can crucially alter protein function in the living
      organism. Modulatory activity coupled with high variation allows us to consider
      propeptides as specific evolutionary modules that can transform biological
      properties of proteases without significant changes in the highly conserved
      catalytic domains. As the considered properties of propeptides are not unique to
      proteases, propeptide-mediated evolution seems to be a universal biological
      mechanism. 

PMID- 25962006
TI  - The epigenetic regulator Cfp1.
AB  - Numerous epigenetic modifications have been identified and correlated with
      transcriptionally active euchromatin or repressed heterochromatin and many
      enzymes responsible for the addition and removal of these marks have been
      characterized. However, less is known regarding how these enzymes are regulated
      and targeted to appropriate genomic locations. Mammalian CXXC finger protein 1 is
      an epigenetic regulator that was originally identified as a protein that binds
      specifically to any DNA sequence containing an unmethylated CpG dinucleotide.
      Mouse embryos lacking CXXC finger protein 1 die prior to gastrulation, and
      embryonic stem cells lacking CXXC finger protein 1 are viable but are unable to
      achieve cellular differentiation and lineage commitment. CXXC finger protein 1 is
      a regulator of both cytosine and histone methylation. It physically interacts
      with DNA methyltransferase 1 and facilitates maintenance cytosine methylation.
      Rescue studies reveal that CXXC finger protein 1 contains redundant functional
      domains that are sufficient to support cellular differentiation and proper levels
      of cytosine methylation. CXXC finger protein 1 is also a component of the Setd1
      histone H3-Lys4 methyltransferase complexes and functions to target these enzymes
      to unmethylated CpG islands. Depletion of CXXC finger protein 1 leads to loss of
      histone H3-Lys4 tri-methylation at CpG islands and inappropriate drifting of this
      euchromatin mark into areas of hetero-chromatin. Thus, one function of CXXC
      finger protein 1 is to serve as an effector protein that interprets cytosine
      methylation patterns and facilitates crosstalk with histone-modifying enzymes. 

PMID- 25962007
TI  - Dynameomics: protein dynamics and unfolding across fold space.
AB  - All currently known structures of proteins together define 'protein fold space'.
      To increase the general understanding of protein dynamics and protein folding, we
      selected a set of 807 proteins and protein domains that represent 95% of the
      currently known autonomous folded domains present in globular proteins. Native
      state and unfolding simulations of these representatives are now complete and
      accessible via a novel database containing over 11 000 simulations. Because
      protein folding is a microscopically reversible process, these simulations
      effectively sample protein folding across all of protein fold space. Here, we
      give an overview of how the representative proteins were selected and how the
      simulations were performed and validated. We then provide examples of different
      types of analyses that can be performed across our large set of simulations, made
      possible by the database approach. We further show how the unfolding simulations
      can be used to compare unfolding of structural elements in isolation and in
      different structural contexts, using as an example a short, triple stranded beta
      sheet that forms the WW domain and is present in several larger unrelated
      proteins. 

PMID- 25962008
TI  - Dissection and prediction of RNA-binding sites on proteins.
AB  - RNA-binding proteins are involved in many important regulatory processes in cells
      and their study is essential for a complete understanding of living organisms.
      They show a large variability from both structural and functional points of view.
      However, several recent studies performed on protein-RNA crystal structures have
      revealed interesting common properties. RNA-binding sites usually constitute
      patches of positively charged or polar residues that make most of the specific
      and non-specific contacts with RNA. Negatively charged or aliphatic residues are
      less frequent at protein-RNA interfaces, although they can also be found either
      forming aliphatic and positive-negative pairs in protein RNA-binding sites or
      contacting RNA through their main chains. Aromatic residues found within these
      interfaces are usually involved in specific base recognition at RNA single-strand
      regions. This specific recognition, in combination with structural
      complementarity, represents the key source for specificity in protein-RNA
      association. From all this knowledge, a variety of computational methods for
      prediction of RNA-binding sites have been developed based either on protein
      sequence or on protein structure. Some reported methods are really successful in
      the identification of RNA-binding proteins or the prediction of RNA-binding
      sites. Given the growing interest in the field, all these studies and prediction
      methods will undoubtedly contribute to the identification and comprehension of
      protein-RNA interactions. 

PMID- 25962009
TI  - Non-neuronal regulation and repertoire of cholinergic receptors in organs.
AB  - Many studies on the cholinergic pathway have indicated that cholinergic
      receptors, which are widely expressed in various cells, play an important role in
      all body organs. In this review, we present the concept that cholinergic
      responses are regulated through a neuronal or non-neuronal mechanism. The
      neuronal mechanism is a system in which acetylcholine binds to cholinergic
      receptors on target cells through the nerves. In the non-neuronal mechanism,
      acetylcholine, produced by neighboring cells in an autocrine/paracrine manner,
      binds to cholinergic receptors on target cells. Both mechanisms subsequently lead
      to physiological and pathophysiological responses. We also investigated the
      subunits/subtypes of cholinergic receptors on target cells, physiological and
      pathophysiological responses of the organs via cholinergic receptors, and
      extracellular factors that alter the subtypes/subunits of cholinergic receptors.
      Collectively, this concept will elucidate how cholinergic responses occur and
      will help us conduct further experiments to develop new therapeutic agents. 

PMID- 25962010
TI  - Oxytocin: recent developments.
AB  - Oxytocin is a neurohypophyseal hormone that is produced centrally by neurons in
      the paraventricular nucleus and supraoptic nucleus of the hypothalamus. It is
      released directly into higher brain centres and into the peripheral circulation
      where it produces a multitude of effects. Classically, oxytocin is known for
      inducing uterine contractions at parturition and milk ejection during suckling.
      Oxytocin also acts in a species and gender specific manner as an important
      neuromodulator. It can affect behaviours associated with stress and anxiety, as
      well social behaviours including sexual and relationship behaviours, and maternal
      care. Additionally, oxytocin has been shown to have a variety of physiological
      roles in peripheral tissues, many of which appear to be modulated largely by
      locally produced oxytocin, dispelling the notion that oxytocin is a purely
      neurohypophyseal hormone. Oxytocin levels are altered in several diseases and the
      use of oxytocin or its antagonists have been identified as a possible clinical
      intervention in the treatment of mood disorders and pain conditions, some
      cancers, benign prostatic disease and osteoporosis. Indeed, oxytocin has already
      been successful in clinical trials to treat autism and schizophrenia. This review
      will report briefly on the known functions of oxytocin, it will discuss in depth
      the data from recent clinical trials and highlight future targets for
      oxytocinergic modulation. 

PMID- 25962012
TI  - The Akt isoforms, their unique functions and potential as anticancer therapeutic
      targets.
AB  - Akt (also known as protein kinase B or PKB) is the major downstream nodal point
      of the PI3K signaling pathway. This pathway is a promising anticancer therapeutic
      target, because constitutive activation of the PI3K-Akt pathway is correlated
      with tumor development, progression, poor prognosis, and resistance to cancer
      therapies. The Akt serine/threonine kinase regulates diverse cellular functions
      including cell growth, proliferation, glucose metabolism, and survival. Although
      all three known Akt isoforms (Akt1-3) are encoded by separate genes, their amino
      acid sequences show a high degree of similarity. For this and other reasons, it
      has long been assumed that all three Akt isoforms are activated in the same way,
      and their functions largely overlap. However, accumulating lines of evidence now
      suggest that the three Akt isoforms might have unique modes of activation and
      many distinct functions. In particular, it has recently been found that the Akt
      isoforms are localized at different subcellular compartments in both adipocytes
      and cancer cells. In this review, we highlight the unique roles of each Akt
      isoform by introducing published data obtained from both in vitro and in vivo
      studies. We also discuss the significant potential of the Akt isoforms as
      effective anticancer therapeutic targets. 

PMID- 25962011
TI  - Liver X receptors and immune regulation.
AB  - Recent studies suggest that homeostasis of lipid metabolism is crucial for the
      function of various immune cells. Oxygenated derivatives of cholesterol
      (oxysterols) are well-known regulators of lipid metabolism and have diverse
      functions, such as inhibition of cholesterol synthesis, efflux of intracellular
      cholesterol, synthesis of cholesterol esters, and activation of liver X receptors
      (LXRs). In this review, we introduce novel roles of the oxysterol receptors LXRs
      in the immune system, including regulation of inflammatory responses, T cell
      expansion, immunoglobulin production, and antitumor responses. We also discuss
      lipid-mediated signaling as a potential target for treatment of immune diseases. 

PMID- 25962013
TI  - New twist in the regulation of cyclin D1.
AB  - Among the cell cycle-related mammalian cyclins, cyclin D1 is more closely
      connected with cell proliferation in response to extracellular signals than the
      cell cycle clock itself. Because both its mRNA and protein are labile, the
      intracellular abundance of cyclin D1 is thought to be largely regulated at the
      level of transcription. However, recent findings suggest that, in certain cell
      types, cyclin D1 is post-translationally regulated, and a disturbance of this
      regulatory mechanism induces aberrant entry into the cell cycle and
      proliferation, sometimes leading to diseases such as cancer. In this review, we
      summarize recent findings and discuss the physiological role and cellular
      function of the novel mechanism of regulation of cyclin D1 in terms of the
      control of cell proliferation. 

PMID- 25962014
TI  - Ceramide synthases in mammalians, worms, and insects: emerging schemes.
AB  - The ceramide synthase (CerS) gene family comprises a group of highly conserved
      transmembrane proteins, which are found in all studied eukaryotes. The key
      feature of the CerS proteins is their role in ceramide synthase activity.
      Therefore, their original name 'longevity assurance gene (Lass) homologs', after
      the founding member, the yeast longevity assurance gene lag1, was altered to
      'CerS'. All CerS have high sequence similarity in a domain called LAG1 motif and
      a subset of CerS proteins is predicted to contain a Homeobox (Hox) domain. These
      domains could be the key to the multiple roles CerS have. CerS proteins play a
      role in diverse biological processes such as proliferation, differentiation,
      apoptosis, stress response, cancer, and neurodegeneration. In this review, we
      focus on CerS structure and biological function with emphasis of biological
      functions in the widely used model systems Caenorhabditis elegans and Drosophila
      melanogaster. Also, we focus on the accumulating data suggesting a role for CerS
      in lipid homeostasis. 

PMID- 25962015
TI  - Revisiting the tubulin folding pathway: new roles in centrosomes and cilia.
AB  - Centrosomes and cilia are critical eukaryotic organelles which have been in the
      spotlight in recent years given their implication in a myriad of cellular and
      developmental processes. Despite their recognized importance and intense study,
      there are still many open questions about their biogenesis and function. In the
      present article, we review the existing data concerning members of the tubulin
      folding pathway and related proteins, which have been identified at centrosomes
      and cilia and were shown to have unexpected roles in these structures. 

PMID- 25962016
TI  - Functional specificity of Akt isoforms in cancer progression.
AB  - Akt/PKB kinases are central mediators of cell homeostasis. There are three highly
      homologous Akt isoforms, Akt1/PKBalpha, Akt2/PKBbeta and Akt3/PKBgamma.
      Hyperactivation of Akt signaling is a key node in the progression of a variety of
      human cancer, by modulating tumor growth, chemoresistance and cancer cell
      migration, invasion and metastasis. It is now clear that, to understand the
      mechanisms on how Akt affects specific cancer cells, it is necessary to consider
      the relative importance of each of the three Akt isoforms in the altered cells.
      Akt1 is involved in tumor growth, cancer cell invasion and chemoresistance and is
      the predominant altered isoform found in various carcinomas. Akt2 is related to
      cancer cell invasion, metastasis and survival more than tumor induction. Most of
      the Akt2 alterations are observed in breast, ovarian, pancreatic and colorectal
      carcinomas. As Akt3 expression is limited to some tissues, its implication in
      tumor growth and resistance to drugs mostly occurs in melanomas, gliomas and some
      breast carcinomas. To explain how Akt isoforms can play different or even opposed
      roles, three mechanisms have been proposed: tissue-specificity
      expression/activation of Akt isoforms, distinct effect on same substrate as well
      as specific localization through the cyto-skeleton network. It is becoming clear
      that to develop an effective anticancer Akt inhibitor drug, it is necessary to
      target the specific Akt isoform which promotes the progression of the specific
      tumor. 

PMID- 25962017
TI  - Antimicrobial peptides from amphibians.
AB  - Increased prevalence of multi-drug resistance in pathogens has encouraged
      researchers to focus on finding novel forms of anti-infective agents.
      Antimicrobial peptides (AMPs) found in animal secretions are components of host
      innate immune response and have survived eons of pathogen evolution. Thus, they
      are likely to be active against pathogens and even those that are resistant to
      conventional drugs. Many peptides have been isolated and shown to be effective
      against multi-drug resistant pathogens. More than 500 AMPs have been identified
      from amphibians. The abundance of AMPs in frog skin is remarkable and constitutes
      a rich source for design of novel pharmaceutical molecules. Expression and post
      translational modifications, discovery, activities and probable therapeutic
      application prospects of amphibian AMPs will be discussed in this article. 

PMID- 25962018
TI  - The role of symmetry in the regulation of bacterial carboxyltransferase.
AB  - Carboxyltransferase is one component of the multifunctional enzyme acetyl-CoA
      carboxylase which catalyzes the first committed step in fatty acid biosynthesis.
      Carboxyltransferase is an alpha2beta2 heterotetramer and possesses two distinct
      but integrated functions. One function catalyzes the transfer of carbon dioxide
      from biotin to acetyl-CoA, whereas the other involves binding to the mRNA
      encoding both subunits. When carboxyltransferase binds to the mRNA both enzymatic
      activity and translation of the mRNA are inhibited. However, the substrate acetyl
      CoA competes with mRNA for binding. Thus, mRNA binding by carboxyltransferase
      provides an effective mechanism for regulating enzymatic activity and gene
      expression. This conceptual review takes the position that regulation of
      enzymatic activity and gene expression of carboxyltransferase by binding to its
      own mRNA is at its most fundamental level the result of the symmetry in the
      chemical reaction catalyzed by the enzyme. The chemical reaction is symmetrical
      in that both substrates generate enolate anions during the course of catalysis.
      The chemical symmetry led to a structural symmetry in the enzyme where both the
      alpha and beta subunits contain oxyanion holes that stabilize the enolate anions.
      Then the region of the mRNA that codes for the oxyanion holes provided the
      binding sites for carboxyltransferase. Thus, the symmetry of the chemical
      reaction formed the foundation for the evolution of the mechanism for regulation
      of carboxyltransferase. 

PMID- 25962020
TI  - Calcineurin inhibitors: status quo and perspectives.
AB  - Despite the fact that cyclosporin A (CsA) and tacrolimus (FK506) are very potent
      drugs in the treatment of serious autoimmune diseases and in the prevention of
      graft vs. host reactions or tissue rejections after allo- or
      xenotransplantations, modern transplantation medicine attempts to develop
      alternative medication regimes without these calcineurin inhibitors. The primary
      motivation for this endeavor is the high incidence of dramatic side effects upon
      immunosuppressive therapy. CsA and FK506 target not only the calcineurin/NFAT
      pathway, but they also bind and inhibit members of distinct peptidyl-prolyl
      cis/trans isomerase families, which are involved in numerous important signal
      transduction pathways. Therefore, the development of a potent calcineurin
      inhibitor that discriminates between calcineurin and other protein phosphatases
      and peptidyl-prolyl cis/trans isomerases, respectively, should improve the drug
      safety in clinical use and represent a valuable tool in basic research to
      investigate calcineurin modulated pathways. This review gives a current overview
      about novel calcineurin inhibitors, which were identified by screening of
      compound libraries and in natural materials or were derived from known inhibitors
      in the past decades. Thereby, we focus on their structure, properties and
      biological effects. 

PMID- 25962019
TI  - Solution NMR studies of periplasmic binding proteins and their interaction
      partners.
AB  - Periplasmic binding proteins (PBPs) are a crucial part of ATP-binding cassette
      import systems in Gram-negative bacteria. Central to their function is the
      ability to undergo a large-scale conformational rearrangement from open
      unliganded to closed-liganded, which signals the presence of substrate and starts
      its translocation. Over the years, PBPs have been extensively studied not only
      owing to their essential role in nutrient uptake but also because they serve as
      excellent models for both practical applications (e.g., biosensor technology) and
      basic research (e.g., allosteric mechanisms). Although much of our knowledge at
      atomic level has been inferred from the detailed, static pictures afforded by
      crystallographic studies, nuclear magnetic resonance (NMR) has been able to fill
      certain gaps in such body of work, particularly with regard to dynamic processes.
      Here, we review NMR studies on PBPs, and their unique insights on conformation,
      dynamics, energetics, substrate binding, and interactions with related transport
      proteins. Based on the analysis of recent paramagnetic NMR results, as well as
      crystallographic and functional observations, we propose a mechanism that could
      explain the ability of certain PBPs to achieve a closed conformation in absence
      of ligand while others seem to remain open until ligand-mediated closure. 

PMID- 25962021
TI  - Interactions of natural polyamines with mammalian proteins.
AB  - The ubiquitously expressed natural polyamines putrescine, spermidine, and
      spermine are small, flexible cationic compounds that exert pleiotropic actions on
      various regulatory systems and, accordingly, are essentially involved in diverse
      life functions. These roles of polyamines result from their capability to
      interact with negatively charged regions of all major classes of biomolecules,
      which might act in response by changing their structures and functions. The
      present review deals with polyamine-protein interactions, thereby focusing on
      mammalian proteins. We discuss the various modes in which polyamines can interact
      with proteins, describe major types of affected functions illustrated by
      representative examples of involved proteins, and support information with
      respective structural evidence from elucidated three-dimensional structures. A
      specific focus is put on polyamine interactions at protein surfaces that can
      modulate the aggregation of proteins to organized structural networks as well as
      to toxic aggregates and, moreover, can play a role in important transient protein
      protein interactions. 

PMID- 25962022
TI  - Cystatins: a versatile family.
AB  - Cystatins are small proteins, typically composed of 100-120 amino acids, which
      together with similar proteins devoid of inhibitory properties, belong to a
      cystatin 'superfamily'. Cystatins can do more than just inhibit proteases: two
      important aspects described here are aggregation properties linked to misfolding
      diseases and the unique ability of monellin, a plant cystatin, to elicit sweet
      taste. The explanation of the puzzling phenomenon of 'sweet proteins' required an
      in-depth structural study of monellin, also regarding the causes of the high
      thermal stability of its single chain structure. The detailed mechanisms by which
      cystatins aggregate could be relevant in the study of misfolding diseases
      involving cystatins. They are reviewed here with emphasis on 3D domain swapping,
      typical of aggregating cystatins. While studying monellin, we noticed that it
      aggregates in a conventional way, probably through the cross-beta spine
      mechanism. However, several cystatins derived from oryzacystatin_I to emulate the
      taste behavior of monellin aggregate via different mechanisms. 

PMID- 25962023
TI  - Human aldo-keto reductases: structure, substrate specificity and roles in
      tumorigenesis.
AB  - The aldo-keto reductase (AKR) superfamily consists of over 150 protein members
      sharing similar structure and enzymatic activities. To date, 13 human AKRs have
      been identified, and they participate in xenobiotic detoxification, biosynthesis
      and metabolism. Increasing evidence suggests the involvement of human AKR
      proteins in cancer development, progression and treatment. Some proteins
      demonstrate multiple functional features in addition to being a reductase for
      carbonyl groups. This review article discusses the most recent progress made in
      the study of humans AKRs. 

PMID- 25962024
TI  - Epigenetherapy, a new concept.
AB  - Small RNAs have been shown to regulate gene transcription by interacting with the
      promoter region and modifying the histone code. The exact mechanism of function
      is still unclear but the feasibility to activate or repress endogenous gene
      expression with small RNA molecules has already been demonstrated in vitro and in
      vivo. In traditional gene therapy non-mutated or otherwise useful genes are
      inserted into patient's cells to treat a disease. In epigenetherapy the action of
      small RNAs is utilized by delivering only the small RNAs to patient's cells where
      they then regulate gene expression by epigenetic mechanisms. This method could be
      widely useful not only for basic research but also for clinical applications of
      small RNAs. 

PMID- 25962025
TI  - Antineuronal autoantibodies in neurological disorders.
AB  - Autoantibodies (abs) related to neurological disease are currently classified
      into two large groups depending on the site of the respective target antigen:
      Group I encompasses abs that recognise intracellular antigens (Hu, Yo, Ri,
      CV2/CRMP5, amphiphysin, Ma2, SOX, ZIC, GAD, adenylate kinase 5, homer 3), whereas
      group II abs are targeted against neuronal cell membrane antigens (VGKC, AMPA-R,
      GABAB-R, NMDA-R, Glycine-R, VGCC, metabotropic GluR1). Both abs groups can be
      further subdivided according to their diagnostic impact for paraneoplastic or non
      paraneoplastic neurological disease. The review gives an overview of the common
      characteristics of each group and provides more detailed information on single
      abs and the associated clinical syndromes. 

PMID- 25962026
TI  - From mammals to viruses: the Schlafen genes in developmental, proliferative and
      immune processes.
AB  - The Schlafen genes have been associated with proliferation control and with
      several differentiation processes, as well as with disparate phenotypes such as
      immune response, embryonic lethality and meiotic drive. They constitute a gene
      family with widespread distribution in mammals, where they are expressed in
      several tissues, predominantly those of the immune system. Moreover, horizontal
      transfer of these genes to orthopoxviruses suggests a role of the viral Schlafens
      in evasion to the host immune response. The expression and functional studies of
      this gene family will be reviewed under the prism of their evolution and
      diversification, the challenges they pose and the future avenues of research. 

PMID- 25962027
TI  - It's a loop world - single strands in RNA as structural and functional elements.
AB  - Unpaired regions in RNA molecules - loops - are centrally involved in defining
      the characteristic three-dimensional (3D) architecture of RNAs and are of high
      interest in RNA engineering and design. Loops adopt diverse, but specific
      conformations stabilised by complex tertiary structural interactions that provide
      structural flexibility to RNA structures that would otherwise not be possible if
      they only consisted of the rigid A-helical shapes usually formed by canonical
      base pairing. By participating in sequence-non-local contacts, they furthermore
      contribute to stabilising the overall fold of RNA molecules. Interactions between
      RNAs and other nucleic acids, proteins, or small molecules are also generally
      mediated by RNA loop structures. Therefore, the function of an RNA molecule is
      generally dependent on its loops. Examples include intermolecular interactions
      between RNAs as part of the microRNA processing pathways, ribozymatic activity,
      or riboswitch-ligand interactions. Bioinformatics approaches have been
      successfully applied to the identification of novel RNA structural motifs
      including loops, local and global RNA 3D structure prediction, and structural and
      conformational analysis of RNAs and have contributed to a better understanding of
      the sequence-structure-function relationships in RNA loops. 

PMID- 25962028
TI  - Protein trans-splicing as a protein ligation tool to study protein structure and
      function.
AB  - Protein trans-splicing (PTS) exerted by split inteins is a protein ligation
      reaction which enables overcoming the barriers of conventional heterologous
      protein production. We provide an overview of the current state-of-the-art in
      split intein engineering, as well as the achievements of PTS technology in the
      realm of protein structure-function analyses, including incorporation of natural
      and artificial protein modifications, controllable protein reconstitution,
      segmental isotope labeling and protein cyclization. We further discuss factors
      crucial for the successful implementation of PTS in these protein engineering
      approaches, and speculate on necessary future endeavours to make PTS a
      universally applicable protein ligation tool. 

PMID- 25962029
TI  - Coiled coils as possible models of protein structure evolution.
AB  - Coiled coils are formed by two or more alpha-helices wrapped around one another.
      This structural motif often guides di-, tri- or multimerization of proteins
      involved in diverse biological processes such as membrane fusion, signal
      transduction and the organization of the cytoskeleton. Although coiled coil
      motifs seem conceptually simple and their existence was proposed in the early
      1950s, the high variability of the motif makes coiled coil prediction from
      sequence a difficult task. They might be confused with intrinsically disordered
      sequences and even more with a recently described structural motif, the charged
      single alpha-helix. By contrast, the versatility of coiled coil structures
      renders them an ideal candidate for protein (re)design and many novel variants
      have been successfully created to date. In this paper, we review coiled coils in
      the light of protein evolution by putting our present understanding of the motif
      and its variants in the context of structural interconversions. We argue that
      coiled coils are ideal subjects for studies of subtle and large-scale structural
      changes because of their well-characterized and versatile nature. 

PMID- 25962030
TI  - Beta-amyloid oligomers: recent developments.
AB  - Recent studies point to a critical role of soluble beta-amyloid oligomers in the
      pathogenesis of one of the most common neurodegenerative diseases, Alzheimer's
      disease (AD). Beta-amyloid peptides are cleavage products of a ubiquitously
      expressed protein, the amyloid precursor protein. Early studies suggested that
      accumulation of extracellular beta-amyloid aggregates are the most toxic species
      causing synaptic dysfunction and neuronal loss in particular regions of the brain
      (neurobiological features underlying cognitive decline of the AD patients). In
      recent years, a shift of pardigm occurred, and now there is accumulating evidence
      that soluble oligomeric forms of the peptide are the most toxic to neuronal
      cells. In this review, we discuss recent findings on the toxic effects of amyloid
      beta oligomers, their physico-chemical properties and the possible pathways of
      their formation in vitro and in vivo. 

PMID- 25962031
TI  - Structure and function of Tec family kinase Itk.
AB  - Itk is a member of the Tec family of kinases that is expressed predominantly in T
      cells. Itk regulates the T cell receptor signaling pathway to modulate T cell
      development and T helper cell differentiation, particularly Th2 differentiation.
      Itk is also important for the development and function of iNKT cells. In this
      review we discuss current progress on our understanding of the structure,
      activation and signaling pathway of Itk, in addition to inhibitors that have been
      developed, which target this kinase. We also place in context the function of
      Itk, available inhibitors and potential use in treating disease. 

PMID- 25962032
TI  - Retinoblastoma family of proteins and chromatin epigenetics: a repetitive story
      in a few LINEs.
AB  - The retinoblastoma (RB) protein family in mammals is composed of three members:
      pRB (or RB1), p107, and p130. Although these proteins do not directly bind DNA,
      they associate with the E2F family of transcription factors which function as DNA
      sequence-specific transcription factors. RB proteins alter gene transcription via
      direct interference with E2F functions, as well as recruitment of transcriptional
      repressors and corepressors that silence gene expression through DNA and histone
      modifications. E2F/RB complexes shape the chromatin landscape through recruitment
      to CpG-rich regions in the genome, thus making E2F/RB complexes function as local
      and global regulators of gene expression and chromatin dynamics. Recruitment of
      E2F/pRB to the long interspersed nuclear element (LINE1) promoter enhances the
      role that RB proteins play in genome-wide regulation of heterochromatin. LINE1
      elements are dispersed throughout the genome and therefore recruitment of RB to
      the LINE1 promoter suggests that LINE1 could serve as the scaffold on which RB
      builds up heterochromatic regions that silence and shape large stretches of
      chromatin. We suggest that mutations in RB function might lead to global
      rearrangement of heterochromatic domains with concomitant retrotransposon
      reactivation and increased genomic instability. These novel roles for RB proteins
      open the epigenetic-based way for new pharmacological treatments of RB-associated
      diseases, namely inhibitors of histone and DNA methylation, as well as histone
      deacetylase inhibitors. 

PMID- 25962033
TI  - Intrinsic neuronal excitability: implications for health and disease.
AB  - The output of a single neuron depends on both synaptic connectivity and intrinsic
      membrane properties. Changes in both synaptic and intrinsic membrane properties
      have been observed during homeostatic processes (e.g., vestibular compensation)
      as well as in several central nervous system (CNS) disorders. Although changes in
      synaptic properties have been extensively studied, particularly with regard to
      learning and memory, the contribution of intrinsic membrane properties to either
      physiological or pathological processes is much less clear. Recent research,
      however, has shown that alterations in the number, location or properties of
      voltage- and ligand-gated ion channels can underlie both normal and abnormal
      physiology, and that these changes arise via a diverse suite of molecular
      substrates. The literature reviewed here shows that changes in intrinsic neuronal
      excitability (presumably in concert with synaptic plasticity) can fundamentally
      modify the output of neurons, and that these modifications can subserve both
      homeostatic mechanisms and the pathogenesis of CNS disorders including epilepsy,
      migraine, and chronic pain. 

PMID- 25962034
TI  - Endoplasmic reticulum quality control and dysmyelination.
AB  - Dysmyelination contributes to several human diseases including multiple
      sclerosis, Charcot-Marie-Tooth, leukodystrophies, and schizophrenia and can
      result in serious neurological disability. Properly formed, compacted myelin
      sheaths are required for appropriate nerve conduction velocities and the health
      and survival of neurons. Many different molecular mechanisms contribute to
      dysmyelination and many of these mechanisms originate at the level of the
      endoplasmic reticulum. The endoplasmic reticulum is a critical organelle for
      myelin biosynthesis and maintenance as the site of myelin protein folding quality
      control, Ca2+ homeostasis, cholesterol biosynthesis, and modulation of cellular
      stress. This review paper highlights the role of the endoplasmic reticulum and
      its resident molecules as an upstream and dynamic contributor to myelin and
      myelin pathologies. 

PMID- 25962035
TI  - The role of CRF family peptides in the regulation of food intake and anxiety-like
      behavior.
AB  - Corticotropin-releasing factor (CRF) and the urocortins (UCN1, UCN2, and UCN3)
      belong to the CRF family of peptides and are the major regulators of the adaptive
      response to internal and external stresses. The actions of CRF and UCNs are
      mediated through two receptor subtypes: CRF receptor 1 (CRFR1) and CRFR2. Their
      physiological roles, among other functions, include the regulation of food intake
      and anxiety-like behavior. In this review, we describe the progress that has been
      made towards understanding how anxiety- and depression-like behavior and food
      intake are regulated by CRF, UCN1, UCN2, and UCN3. 

PMID- 25962036
TI  - Compensated pathogenic deviations.
AB  - Deleterious or 'disease-associated' mutations are mutations that lead to disease
      with high phenotype penetrance: they are inherited in a simple Mendelian manner,
      or, in the case of cancer, accumulate in somatic cells leading directly to
      disease. However, in some cases, the amino acid that is substituted resulting in
      disease is the wild-type native residue in the functionally equivalent protein in
      another species. Such examples are known as 'compensated pathogenic deviations'
      (CPDs) because, somewhere in the second species, there must be compensatory
      mutations that allow the protein to function normally despite having a residue
      which would cause disease in the first species. Depending on the nature of the
      mutations, compensation can occur in the same protein, or in a different protein
      with which it interacts. In principle, compensation can be achieved by a single
      mutation (most probably structurally close to the CPD), or by the cumulative
      effect of several mutations. Although it is clear that these effects occur in
      proteins, compensatory mutations are also important in RNA potentially having an
      impact on disease. As a much simpler molecule, RNA provides an interesting model
      for understanding mechanisms of compensatory effects, both by looking at
      naturally occurring RNA molecules and as a means of computational simulation.
      This review surveys the rather limited literature that has explored these
      effects. Understanding the nature of CPDs is important in understanding traversal
      along fitness landscape valleys in evolution. It could also have applications in
      treating diseases that result from such mutations. 

PMID- 25962037
TI  - DNA binding proteins: outline of functional classification.
AB  - DNA-binding proteins composed of DNA-binding domains directly affect genomic
      functions, mainly by performing transcription, DNA replication or DNA repair.
      Here, we briefly describe the DNA-binding proteins according to these three major
      functions. Transcription factors that usually bind to specific sequences of DNA
      could be classified based on their sequence similarity and the structure of the
      DNA-binding domains, such as basic, zinc-coordinating, helix-turn-helix domains,
      etc. Most DNA replication factors do not need a specific sequence of DNA, but
      instead mainly depend on a DNA structure, with the exception of the origin
      recognition complex in yeast or Escherichia coli that recognizes the DNA
      sequences at particular origins. DNA replication includes initiation and
      elongation. The major DNA-binding proteins involved in these two steps are
      briefly described. DNA repair proteins bound to DNA depend on the damaged DNA
      structure. They are classified to base excision repair, DNA mismatch repair,
      nucleotide excision repair, homologous recombination repair and non-homologous
      end joining. The major DNA-binding proteins involved in these pathways are
      briefly described. Histone and high mobility group are two examples of DNA
      binding proteins that do not belong to the three categories above and are briefly
      described. Finally, we warn that the non-specific binding proteins might have an
      affinity to some non-specific medium materials such as protein A or G beads that
      are commonly used for immune precipitation, which can easily generate false
      positive signals while detecting protein-protein interaction; therefore, the
      results need to be carefully analyzed using positive/negative controls. 

PMID- 25962038
TI  - Structure, dynamics, and mechanism of the lead-dependent ribozyme.
AB  - Leadzyme is a small catalytic RNA that was identified by in vitro selection for
      Pb2+-dependent cleavage from a tRNA library. Leadzyme employs a unique two-step
      Pb2+-specific mechanism to cleave within its active site. NMR and crystal
      structures of the active site revealed different folding patterns, but neither
      features the in-line alignment for attack by the 2'-OH nucleophilic group. These
      experimentally determined structures most likely represent ground states and are
      catalytically inactive. There are significant dynamics of the active site and the
      motif samples multiple conformations at the ground states. Various metal ion
      binding sites have been identified, including one that may be occupied by a
      catalytic Pb2+. Based on functional group analysis, a computational model of the
      transition state has been proposed. This model features a unique base triple that
      is consistent with sequence and functional group requirements for catalysis. This
      structure is likely only populated transiently, but imposing appropriate
      conformational constraints may significantly stabilize this state thereby
      promoting catalysis. Other ions may inhibit the cleavage by competing for the
      Pb2+ binding site, or by stabilizing the ground state thereby suppressing its
      transition to the catalytically active conformation. Some rare earth ions can
      enhance the reaction via an unknown mechanism. Because of its unique chemistry
      and dynamic behavior, leadzyme can continue to serve as an excellent model system
      for teaching us RNA biology and chemistry. 

PMID- 25962039
TI  - The function and architecture of DEAH/RHA helicases.
AB  - Helicases are ubiquitous enzymes that participate in every aspect of nucleic acid
      metabolism. The DEAH/RHA family of helicases are involved in a variety of
      cellular processes including transcriptional and translational regulation, pre
      mRNA splicing, pre-rRNA processing, mRNA export and decay, in addition to the
      innate immune response. Recently, the first crystal structures of a DEAH/RHA
      helicase unveiled the unique structural features of this helicase family. These
      structures furthermore illuminate the molecular mechanism of these proteins and
      provide a framework for analysis of their interaction with nucleic acids,
      regulatory proteins and large macromolecular complexes. 

PMID- 25962040
TI  - The discovery and mechanism of sweet taste enhancers.
AB  - Excess sugar intake posts several health problems. Artificial sweeteners have
      been used for years to reduce dietary sugar content, but they are not ideal
      substitutes for sugar owing to their off-taste. A new strategy focused on
      allosteric modulation of the sweet taste receptor led to identification of sweet
      taste 'enhancers' for the first time. The enhancer molecules do not taste sweet,
      but greatly potentiate the sweet taste of sucrose and sucralose selectively.
      Following a similar mechanism as the natural umami taste enhancers, the sweet
      enhancer molecules cooperatively bind with the sweeteners to the Venus flytrap
      domain of the human sweet taste receptor and stabilize the active conformation.
      Now that the approach has proven successful, enhancers for other sweeteners and
      details of the molecular mechanism for the enhancement are being actively
      pursued. 

PMID- 25962041
TI  - Evolvability, epigenetics and transposable elements.
AB  - Evolvability can be defined as the capacity of an individual to evolve and thus
      to capture adaptive mutations. Transposable elements (TE) are an important source
      of mutations in organisms. Their capacity to transpose within a genome, sometimes
      at a high rate, and their copy number regulation are environment-sensitive, as
      are the epigenetic pathways that mediate TE regulation in a genome. In this
      review we revisit the way we see evolvability with regard to transposable
      elements and epigenetics. 

PMID- 25962042
TI  - Fragile X family members have important and non-overlapping functions.
AB  - The fragile X family of genes encodes a small family of RNA binding proteins
      including FMRP, FXR1P and FXR2P that were identified in the 1990s. All three
      members are encoded by 17 exons and show alternative splicing at the 3' ends of
      their respective transcripts. They share significant homology in the protein
      functional domains, including the Tudor domains, the nuclear localization
      sequence, a protein-protein interaction domain, the KH1 and KH2 domains and the
      nuclear export sequence. Fragile X family members are found throughout the animal
      kingdom, although all three members are not consistently present in species
      outside of mammals: only two family members are present in the avian species
      examined, Gallus gallus and Taeniopygia guttata, and in the frog Xenopus
      tropicalis. Although present in many tissues, the functions of the fragile X
      family members differ, which are particularly evident in knockout studies
      performed in animals. The fragile X family members play roles in normal neuronal
      function and in the case of FXR1, in muscle function. 

PMID- 25962043
TI  - Oxidative folding: recent developments.
AB  - Disulfide bond formation in proteins is an effective tool of both structure
      stabilization and redox regulation. The prokaryotic periplasm and the endoplasmic
      reticulum of eukaryotes were long considered as the only compartments for enzyme
      mediated formation of stable disulfide bonds. Recently, the mitochondrial
      intermembrane space has emerged as the third protein-oxidizing compartment. The
      classic view on the mechanism of oxidative folding in the endoplasmic reticulum
      has also been reshaped by new observations. Moreover, besides the structure
      stabilizing function, reversible disulfide bridge formation in some proteins of
      the endoplasmic reticulum, seems to play a regulatory role. This review briefly
      summarizes the present knowledge of the redox systems supporting oxidative
      folding, emphasizing recent developments. 

PMID- 25962044
TI  - Functional aspects of cytidine-guanosine dinucleotides and their locations in
      genes.
AB  - Originally, the finding of a particular distribution of cytidine-guanosine
      dinucleotides (CpGs) in genomic DNA was considered to be an interesting
      structural feature of eukaryotic genome organization. Despite a global depletion
      of CpGs, genes are frequently associated with CpG clusters called CpG islands
      (CGIs). CGIs are prevalently unmethylated but often found methylated in
      pathologic situations. On the other hand, CpGs outside of CGIs are generally
      methylated and are found mainly in the heterochromatic fraction of the genome.
      Hypomethylation of those CpGs is associated with genomic instability in
      malignancy. Additionally, CpG-rich and CpG-poor regions, as well as CpG-shores,
      are defined. Usually, the methylation status inversely correlates with gene
      expression. Methylation of CpGs, as well as demethylation and generation of
      hydroxmethyl-cytosines, is strictly regulated during development and
      differentiation. This review deals with the relevance of the organizational
      features of CpGs and their relation to each other. 

PMID- 25962045
TI  - Ion transport and osmotic adjustment in plants and bacteria.
AB  - Plants and bacteria respond to hyperosmotic stress by an increase in
      intracellular osmolality, adjusting their cell turgor to altered growth
      conditions. This can be achieved either by increased uptake or de novo synthesis
      of a variety of organic osmolytes (so-called 'compatible solutes'), or by
      controlling fluxes of ions across cellular membranes. The relative contributions
      of each of these mechanisms have been debated in literature for many years and
      remain unresolved. This paper summarises all the arguments and reopens a
      discussion on the efficiency and strategies of osmotic adjustment in plants and
      bacteria. We show that the bulk of osmotic adjustment in both plants and bacteria
      is achieved by increased accumulation of inorganic osmolytes such as K+, Na+ and
      Cl-. This is applicable to both halophyte and glycophyte species. At the same
      time, de novo synthesis of compatible solutes is an energetically expensive and
      slow option and can be used only for the fine adjustment of the cell osmotic
      potential. The most likely role the organic osmolytes play in osmotic adjustment
      is in osmoprotection of key membrane transport proteins and reactive oxygen
      species (ROS) scavenging. The specific mechanisms by which compatible solutes
      regulate activity of ion transporters remain elusive and require more thorough
      investigation. It is concluded that creating transgenic species with increased
      levels of organic osmolytes by itself is counterproductive due to high yield
      penalties; all these attempts should be complemented by a concurrent increase in
      the accumulation of inorganic ions directly used for osmotic adjustment. 

PMID- 25962046
TI  - Functional and evolutional implications of natural channel-enzyme fusion
      proteins.
AB  - Channeling of ions or substrates across membranes and enzymatic activity are two
      highly distinct biochemical concepts. They are usually studied by different
      research groups, which focus on either subject. Nature has provided a challenge
      for specialized scientists by fusing genes coding for a transmembrane channel
      domain with an enzyme domain. There are examples of fusion proteins consisting of
      an N-terminal ion channel or sensor and a C-terminal, cytosolic kinase domain (or
      other enzymes involved in signaling) of which either domain may influence the
      functionality of the other. The physiological role of such fusions may reside in
      coupling ion flux or membrane potential sensing to cellular responses or vice
      versa. Other examples can be found in metabolism. We have identified and
      characterized an ar-senite-conducting aquaglyceroporin carrying a C-terminal ar
      senate reductase domain. Here, a function in the detoxification of arsenic is
      obvious, with the enzyme domain generating the substrate for the channel domain,
      which immediately shuttles the toxic metabolite out of the cell. We see two
      advantages in this latter concept: lowering of the cellular toxicity due to rapid
      release of the substrate and energetic coupling of the reaction enthalpy to
      extrusion due to high local substrate gradients. In this overview, we summarize
      and discuss the current view on functional and physiological aspects of
      channel/enzyme fusion proteins. 

PMID- 25962047
TI  - Insulin resistance and epigenetic regulation: insights from human studies and
      prospects for future research.
AB  - In this study, we review the current knowledge and recent insights on the role of
      epigenetic factors in the development of human insulin resistance (IR)- and
      metabolic syndrome (MS)-related phenotypes, and attempt to lay a framework to
      consider IR as a potentially reversible incapacity to control metabolic
      homeostasis that is strongly influenced by the interplay between external and
      internal cues. We summarize the evidence on how tissue-specific epigenetic
      markers participate either by activating or repressing the gene expression
      programs to modulate IR- and MS-associated traits. Some additional data are
      provided about how the exploration of DNA methylation markers in peripheral blood
      mononuclear cells potentially offers appealing information about the impact of
      epigenetics in the pathogenesis of IR. Clues about the relation between IR and
      impaired intrauterine growth explained by fetal metabolic programming and
      epigenetic modifications are shown, including novel findings about the impact of
      histone modifications. For instance, we observed that specific epigenetic factors
      in genes associated with mitochondrial biogenesis may be associated with birth
      weight. Furthermore, some prospective ideas about the functional consequences of
      genetic variation modulated by allele-specific epigenetic markers and its impact
      on MS susceptibility are also illustrated. Finally, we summarize the current
      knowledge of epigenetics as the biological rationale for potential therapeutic
      intervention in IR and MS. 

PMID- 25962049
TI  - Telocytes.
AB  - Here, we review the history, morphology, immunohistochemical phenotype, and
      presumptive roles of a new type of interstitial tissue cells, formerly called
      interstitial Cajal-like cells (ICLC) and by 2010 named 'telocytes' (TC). Many
      different techniques have been used to characterize TC and provide their
      unequivocal identification: (i) in vitro, cultures and isolated cells; (ii) in
      situ, fixed specimens examined by light and fluorescence microscopy, transmission
      (TEM) and scanning electron microscopy, and electron tomography. TEM allowed sure
      identification and characterization of the most peculiar feature of TC: the long,
      thin, and convoluted prolongations named 'telopodes'. An enormous variety of
      antibodies have been tested, but presently none are reliable to specifically
      label TC. TC have a mesenchymal origin and are resident connective tissue
      (stromal) cells. Possible identification with 'already identified' stromal cell
      types (fibroblasts, fibrocytes, fibroblast-like cells, and mesenchymal stromal
      cells) is discussed. We conclude that in adulthood, most of the TC have the
      morphology of fibrocytes. Apparently, immunocytochemistry suggests that a variety
      of TC populations showing different, likely organ-specific, immunophenotypes
      might exist. Several roles have been hypothesized for TC: mechanical roles,
      intercellular signaling, guiding and nursing of immature cells during
      organogenesis, and being themselves a pool of precursors for many of the
      mesenchyme-derived cells in adulthood; however, none of these roles have been
      proven yet. On the basis of the available data, we propose TC may be key players
      in organ regeneration and repair. 

PMID- 25962048
TI  - DNA methylation: dynamic and stable regulation of memory.
AB  - Epigenetic mechanisms have emerged as a central process in learning and memory.
      Histone modifications and DNA methy-lation are epigenetic events that can mediate
      gene transcription. Interesting features of these epigenetic changes are their
      transient and long lasting potential. Recent advances in neuroscience suggest
      that DNA methylation is both dynamic and stable, mediating the formation and
      maintenance of memory. In this review, we will further illustrate the recent
      hypothesis that DNA methylation participates in the transcriptional regulation
      necessary for memory. 

PMID- 25962050
TI  - mRNA degradation and maturation in prokaryotes: the global players.
AB  - The degradation of messenger RNA is of universal importance for controlling gene
      expression. It directly affects protein synthesis by modulating the amount of
      mRNA available for translation. Regulation of mRNA decay provides an efficient
      means to produce just the proteins needed and to rapidly alter patterns of
      protein synthesis. In bacteria, the half-lives of individual mRNAs can differ by
      as much as two orders of magnitude, ranging from seconds to an hour. Most of what
      we know today about the diverse mechanisms of mRNA decay and maturation in
      prokaryotes comes from studies of the two model organisms Escherichia coli and
      Bacillus subtilis. Their evolutionary distance provided a large picture of
      potential pathways and enzymes involved in mRNA turnover. Among them are three
      ribonucleases, two of which have been discovered only recently, which have a
      truly general role in the initiating events of mRNA degradation: RNase E, RNase J
      and RNase Y. Their enzymatic characteristics probably determine the strategies of
      mRNA metabolism in the organism in which they are present. These ribonucleases
      are coded, alone or in various combinations, in all prokaryotic genomes, thus
      reflecting how mRNA turnover has been adapted to different ecological niches
      throughout evolution. 

PMID- 25962051
TI  - The Tat-dependent protein translocation pathway.
AB  - The twin-arginine translocation (Tat) pathway is found in bacteria, archaea, and
      plant chloroplasts, where it is dedicated to the transmembrane transport of fully
      folded proteins. These proteins contain N-terminal signal peptides with a
      specific Tat-system binding motif that is recognized by the transport machinery.
      In contrast to other protein transport systems, the Tat system consists of
      multiple copies of only two or three usually small (~8-30 kDa) membrane proteins
      that oligomerize to two large complexes that transiently interact during
      translocation. Only one of these complexes includes a polytopic membrane protein,
      TatC. The other complex consists of TatA. Tat systems of plants, proteobacteria,
      and several other phyla contain a third component, TatB. TatB is evolutionarily
      and structurally related to TatA and usually forms tight complexes with TatC.
      Minimal two-component Tat systems lacking TatB are found in many bacterial and
      archaeal phyla. They consist of a 'bifunctional' TatA that also covers TatB
      functionalities, and a TatC. Recent insights into the structure and interactions
      of the Tat proteins have various important implications. 

PMID- 25962052
TI  - Autotransporter protein secretion.
AB  - Autotransporter proteins are a large family of virulence factors secreted from
      Gram-negative bacteria by a unique mechanism. First described in the 1980s, these
      proteins have a C-terminal region that folds into a beta-barrel in the bacterial
      outer membrane. The so-called passenger domain attached to this barrel projects
      away from the cell surface and may be liberated from the cell by self-cleavage or
      surface proteases. Although the majority of passenger domains have a similar beta
      helical structure, they carry a variety of sub-domains, allowing them to carry
      out widely differing functions related to pathogenesis. Considerable biochemical
      and structural characterisation of the barrel domain has shown that
      'autotransporters' in fact require a conserved and essential protein complex in
      the outer membrane for correct folding. Although the globular domains of this
      complex projecting into the periplasmic space have also been structurally
      characterised, the overall secretion pathway of the autotransporters remains
      highly puzzling. It was presumed for many years that the passenger domain passed
      through the centre of the barrel domain to reach the cell surface, driven at
      least in part by folding. This picture is complicated by conflicting data, and
      there is currently little hard information on the true nature of the secretion
      intermediates. As well as their medical importance therefore, autotransporters
      are proving to be an excellent system to study the folding and membrane insertion
      of outer membrane proteins in general. This review focuses on structural aspects
      of autotransporters; their many functions in pathogenesis are beyond its scope. 

PMID- 25962053
TI  - Origin and function of embryonic Sertoli cells.
AB  - In the adult testis, Sertoli cells (SCs) are the epithelial supporting cells of
      the seminiferous tubules that provide germ cells (GCs) with the required
      nutrients and structural and regulatory support to complete spermatogenesis. SCs
      also form the blood-testis barrier, phagocytose apoptotic spermatocytes and cell
      debris derived from spermiogenesis, and produce and secrete numerous paracrine
      and endocrine signals involved in different regulatory processes. In addition to
      their essential functions in the adult testis, SCs play a pivotal role during
      testis development. They are the first cells to differentiate in the embryonic XY
      gonadal primordium and are involved in the regulation of testis-specific
      differentiation processes, such as prevention of GC entry into meiosis, Leydig
      and peritubular myoid cell differentiation, and regression of the Mullerian duct,
      the anlagen of the uterus, oviducts, and the upper part of the vagina. Expression
      of the Y-linked gene SRY in pre-SCs initiates a genetic cascade that leads to SC
      differentiation and subsequently to testis development. Since the identification
      of the SRY gene, many Sertoli-specific transcription factors and signals
      underlying the molecular mechanisms of early testis differentiation have been
      identified. Here, we review the state of the art of the molecular interactions
      that commit the supporting cell lineage of the gonadal primordium to
      differentiate as SCs and the subsequent Sertoli-specific signaling pathways
      involved in early testis differentiation. 

PMID- 25962054
TI  - MicroRNA-125a influences breast cancer stem cells by targeting leukemia
      inhibitory factor receptor which regulates the Hippo signaling pathway.
AB  - Cancer stem cells (CSC) are the main driving force behind cancer initiation and
      progression. The molecular mechanisms that regulate CSC properties are poorly
      understood. MicroRNAs (miRNAs) play a significant role in normal and cancer
      tissues. Here, we show that miRNA-125a indirectly regulates TAZ, an effector
      molecule in the Hippo pathway, through the leukemia inhibitory factor receptor
      (LIFR). The miR-125a->LIFR axis affected the homeostasis of nonmalignant and
      malignant breast epithelial stem cells through the Hippo signaling pathway.
      Inhibition of miR-125a in breast cancer cells led to a significant reduction in
      the CSC pool. In contrast, enhanced expression of miR-125a in nonmalignant breast
      epithelial cells resulted in significant expansion of the stem cell pool. Gain of
      function and loss of function of LIFR directly correlated with the inhibition and
      overexpression of miR-125a, respectively. Modulation of miR-125a led to a change
      in the activity of TAZ and its subcellular localization. We further demonstrated
      that miR-125a influenced stem cells by regulating Hippo signaling through LIFR in
      human primary breast cancer cells confirming the data obtained from established
      cell lines. We suggest that miR-125a could be a potential target against CSCs
      that maybe used along with the existing conventional therapies. 

PMID- 25962055
TI  - International Child Health Competencies.

PMID- 25962057
TI  - Advancing Care for Lesbian, Gay, Bisexual, and Transgender Persons: Enough
      Already?

PMID- 25962056
TI  - Comparative Safety of Testosterone Dosage Forms.
AB  - IMPORTANCE: Increases in testosterone use and mixed reports of adverse events
      have raised concerns about the cardiovascular safety of testosterone.
      Testosterone is available in several delivery mechanisms with varying
      pharmacokinetics; injections cause spikes in testosterone levels, and transdermal
      patches and gels cause more subtle but sustained increases. The comparative
      cardiovascular safety of gels, injections, and patches has not been studied.
      OBJECTIVE: To determine the comparative cardiovascular safety of testosterone
      injections, patches, and gels. DESIGN, SETTING, AND PARTICIPANTS: A retrospective
      cohort study was conducted using administrative claims from a commercially
      insured (January 1, 2000, to December 31, 2012) and Medicare (January 1, 2007, to
      December 31, 2010) population in the United States and general practitioner
      records from the United Kingdom (January 1, 2000, to June 30, 2012). Participants
      included men (aged >=18 years) who initiated use of testosterone patches, gels,
      or injections following 180 days with no testosterone use. Our analysis was
      conducted from December 11, 2013, to November 12, 2014. EXPOSURES: New initiation
      of a testosterone dosage form, with use monitored for up to 1 year. MAIN OUTCOMES
      AND MEASURES: Inpatient or outpatient medical records, diagnoses, or claims for
      cardiovascular and cerebrovascular events including myocardial infarction (MI),
      unstable angina, stroke, and composite acute event (MI, unstable angina, or
      stroke); venous thromboembolism (VTE); mortality; and all-cause hospitalization.
      RESULTS: We identified 544,115 testosterone initiators between the 3 data sets:
      37.4% injection, 6.9% patch, and 55.8% gel. The majority of men in the Medicare
      cohort were injection initiators (51.2%), most in the US commercially insured
      population were gel initiators (56.5%), and the UK database included equal
      proportions of injections and gel users (approximately 41%). With analysis
      conducted using hazard ratios and 95% CIs, compared with men using gels,
      injection initiators had higher hazards of cardiovascular events (ie, MI,
      unstable angina, and stroke) (1.26; 1.18-1.35), hospitalization (1.16; 1.13
      1.19), and death (1.34; 1.15-1.56) but not VTE (0.92; 0.76-1.11). Compared with
      gels, patches did not confer increased hazards of cardiovascular events (1.10;
      0.94-1.29), hospitalization (1.04; 1.00-1.08), death (1.02; 0.77-1.33), or VTE
      (1.08; 0.79-1.47). CONCLUSIONS AND RELEVANCE: Testosterone injections were
      associated with a greater risk of cardiovascular events, hospitalizations, and
      deaths compared with gels. Patches and gels had similar risk profiles. However,
      this study did not assess whether patients met criteria for use of testosterone
      and did not assess the safety of testosterone among users compared with nonusers
      of the drug.

PMID- 25962058
TI  - Overexpression of the Promigratory and Prometastatic PTK7 Receptor Is Associated
      with an Adverse Clinical Outcome in Colorectal Cancer.
AB  - Biomarkers and novel therapeutic targets are urgently needed in colorectal cancer
      (CRC). The pseudo tyrosine kinase receptor 7 (PTK7) is involved in planar cell
      polarity and it is deregulated in various malignancies, including CRC. Yet,
      little is known about its protein expression in human CRC, or about a possible
      correlation of its expression with clinical endpoints. Using a clinically
      annotated Tissue MicroArray (TMA) produced from from 192 consecutive CRC patients
      treated by initial surgery, we examined PTK7 expression by immunohistochemistry
      in tumoral tissue and matched normal mucosae, and correlated its expression with
      clinico-pathological features and patient outcome. PTK7 depletion by specific
      shRNA in HCT116 and HCT15 CRC cell lines was found to affect cell proliferation,
      resistance to drugs and cell migration. Tumor growth and metastatic phenotype
      were investigated in vivo using a xenograft mouse model of CRC cells with
      modulated expression of PTK7 levels. PTK7 was significantly up-regulated in CRC
      tissue as compared to matched healthy mucosae, and significant overexpression was
      found in 34% of patients. PTK7 overexpression was significantly associated with a
      reduced metastasis-free survival in non-metastatic patients. In HCT116 and HCT15
      cells, shRNA PTK7 reduced migration but did not affect cell proliferation and
      resistance to drugs. In a xenograft mouse of HCT15 cells, downregulation of PTK7
      led to reduced tumor growth, whereas its overexpression in PTK7-negative cancer
      cells led to increased metastatic events. PTK7 expression thus represents a
      potential prognostic biomarker and a novel therapeutic target in CRC. 

PMID- 25962059
TI  - Identification of CD4-Binding Site Dependent Plasma Neutralizing Antibodies in an
      HIV-1 Infected Indian Individual.
AB  - Dissecting antibody specificities in the plasma of HIV-1 infected individuals
      that develop broadly neutralizing antibodies (bNAbs) is likely to provide useful
      information for refining target epitopes for vaccine design. Several studies have
      reported CD4-binding site (CD4bs) antibodies as neutralization determinants in
      the plasma of subtype B-infected individuals; however there is little information
      on the prevalence of CD4bs specificities in HIV-infected individuals in India.
      Here, we report on the presence of CD4bs antibodies and their contribution to
      virus neutralization in the plasma from a cohort of HIV-1 infected Indian
      individuals. Plasma from 11 of the 140 HIV-1 infected individuals (7.9%) studied
      here exhibited cross-neutralization activity against a panel of subtype B and C
      viruses. Analyses of these 11 plasma samples for the presence of CD4bs antibodies
      using two CD4bs-selective probes (antigenically resurfaced HXB2gp120 core protein
      RSC3 and hyperglycosylated JRFLgp120 mutant DeltaN2mCHO) revealed that five
      (AIIMS 617, 619, 627, 642, 660) contained RSC3-reactive plasma antibodies and
      only one (AIIMS 660) contained DeltaN2mCHO-reactive antibodies. Plasma antibody
      depletion and competition experiments confirmed that the neutralizing activity in
      the AIIMS 660 plasma was dependent on CD4bs antibodies. To the best of our
      knowledge, this is the first study to report specifically on the presence of
      CD4bs antibodies in the plasma of a cohort of HIV-1 infected Indian donors. The
      identification of CD4bs dependent neutralizing antibodies in an HIV-1 infected
      Indian donor is a salient finding of this study and is supportive of ongoing
      efforts to induce similar antibodies by immunization. 

PMID- 25962061
TI  - Correction: Comparison of the Japanese Orthopaedic Association (JOA) Score and
      Modified JOA (mJOA) Score for the Assessment of Cervical Myelopathy: A
      Multicenter Observational Study.

PMID- 25962060
TI  - Prognostic Value of Malic Enzyme and ATP-Citrate Lyase in Non-Small Cell Lung
      Cancer of the Young and the Elderly.
AB  - BACKGROUND: Lung cancer is the leading cause of death among malignancies
      worldwide. Understanding its biology is therefore of pivotal importance to
      improve patient's prognosis. In contrast to non-neoplastic tissues, cancer cells
      utilize glucose mainly for production of basic cellular modules '(i.e.
      nucleotides, aminoacids, fatty acids). In cancer, Malic enzyme (ME) and ATP
      citrate lyase (ACLY) are key enzymes linking aerobic glycolysis and fatty acid
      synthesis and may therefore be of biological and prognostic significance in non
      small cell lung cancer (NSCLC). MATERIAL AND METHODS: ME and ACLY expression was
      analyzed in 258 NSCLC in correlation with clinico-pathological parameters
      including patient's survival. RESULTS: Though, overall expression of both enzymes
      correlated positively, ACLY was associated with local tumor stage, whereas ME
      correlated with occurrence of mediastinal lymph node metastases. Young patients
      overexpressing ACLY and/or ME had a significantly longer overall survival. This
      proved to be an independent prognostic factor. This contrasts older NSCLC
      patients, in whom overexpression of ACLY and/or ME appears to predict the
      opposite. CONCLUSION: In NSCLC, ME and ACLY show different enzyme expressions
      relating to local and mediastinal spread. Most important, we detected an inverse
      prognostic impact of ACLY and/or ME overexpression in young and elderly patients.
      It can therefore be expected, that treatment of NSCLC especially, if targeting
      metabolic pathways, requires different strategies in different age groups.

PMID- 25962063
TI  - Time Dependent MHD Nano-Second Grade Fluid Flow Induced by Permeable Vertical
      Sheet with Mixed Convection and Thermal Radiation.
AB  - The aim of present paper is to study the series solution of time dependent MHD
      second grade incompressible nanofluid towards a stretching sheet. The effects of
      mixed convection and thermal radiation are also taken into account. Because of
      nanofluid model, effects Brownian motion and thermophoresis are encountered. The
      resulting nonlinear momentum, heat and concentration equations are simplified
      using appropriate transformations. Series solutions have been obtained for
      velocity, temperature and nanoparticle fraction profiles using Homotopy Analysis
      Method (HAM). Convergence of the acquired solution is discussed critically.
      Behavior of velocity, temperature and concentration profiles on the prominent
      parameters is depicted and argued graphically. It is observed that temperature
      and concentration profiles show similar behavior for thermophoresis parameter Nut
      but opposite tendency is noted in case of Brownian motion parameter Nub. It is
      further analyzed that suction parameter S and Hartman number MU depict decreasing
      behavior on velocity profile. 

PMID- 25962062
TI  - Genetic testing of Korean familial hypercholesterolemia using whole-exome
      sequencing.
AB  - Familial hypercholesterolemia (FH) is a genetic disorder with an increased risk
      of early-onset coronary artery disease. Although some clinically diagnosed FH
      cases are caused by mutations in LDLR, APOB, or PCSK9, mutation detection rates
      and profiles can vary across ethnic groups. In this study, we aimed to provide
      insight into the spectrum of FH-causing mutations in Koreans. Among 136 patients
      referred for FH, 69 who met Simon Broome criteria with definite family history
      were enrolled. By whole-exome sequencing (WES) analysis, we confirmed that the 3
      known FH-related genes accounted for genetic causes in 23 patients (33.3%). A
      substantial portion of the mutations (19 of 23 patients, 82.6%) resulted from 17
      mutations and 2 copy number deletions in LDLR gene. Two mutations each in the
      APOB and PCSK9 genes were verified. Of these anomalies, two frameshift deletions
      in LDLR and one mutation in PCSK9 were identified as novel causative mutations.
      In particular, one novel mutation and copy number deletion were validated by co
      segregation in their relatives. This study confirmed the utility of genetic
      diagnosis of FH through WES. 

PMID- 25962065
TI  - Expression, purification and auto-activation of cathepsin E from insect cells.
AB  - Cathepsin E is an aspartic protease that belongs to the pepsin family. This
      protease is similar to cathepsin D but differs in its tissue distribution and
      cell localization. Elevated levels of this enzyme are linked to several tumors,
      including devastating pancreatic ductal adenocarcinoma. In this manuscript, we
      present a new protocol for the high-yield purification of recombinant human
      cathepsin E in the baculovirus expression system. The recombinant protein was
      produced by the Sf9 insect cell line and secreted into the medium in the form of
      an inactive zymogen. Procathepsin E was purified using ion-exchange and size
      exclusion chromatographies followed by pepstatin- and heparin-affinity
      chromatography steps. The zymogen was activated at an acidic pH, resulting in a
      high yield of the activated intermediate of cathepsin E. The enzymatic activity,
      stability, and molecular weight corresponded to those of cathepsin E. The new
      purification procedure will promote further studies of this enzyme to improve the
      understanding of its structure-function relationship and consequently enable the
      development of better therapeutic approaches. 

PMID- 25962064
TI  - Human Copper Chaperone Atox1 Translocates to the Nucleus but does not Bind DNA In
      Vitro.
AB  - After Ctr1-mediated cell uptake, copper (Cu) is transported by the cytoplasmic Cu
      chaperone Atox1 to P1B type ATPases ATP7A and ATP7B in the Golgi network, for
      incorporation into Cudependent enzymes. Atox1 is a small 68-residue protein that
      binds Cu in a conserved CXXC motif; it delivers Cu to target domains in ATP7A/B
      via direct protein-protein interactions. Specific transcription factors
      regulating expression of the human Cu transport proteins have not been reported
      although Atox1 was recently suggested to have dual functionality such that it, in
      addition to its cytoplasmic chaperone function, acts as a transcription factor in
      the nucleus. To examine this hypothesis, here we investigated the localization of
      Atox1 in HeLa cells using fluorescence imaging in combination with in vitro
      binding experiments to fluorescently labeled DNA duplexes harboring the proposed
      promotor sequence. We found that whereas Atox1 is present in the nucleus in HeLa
      cells, it does not bind to DNA in vitro. It appears that Atox1 mediates
      transcriptional regulation via additional (unknown) proteins. 

PMID- 25962066
TI  - 28-mer Fragment Derived from Enterocin CRL35 Displays an Unexpected Bactericidal
      Effect on Listeria Cells.
AB  - Two shorter peptides derived from enterocin CRL35, a 43-mer bacteriocin, were
      synthesized i.e. the N-terminal fragment spanning from residues 1 to 15, and a 28
      mer fragment that represents the C-terminal of enterocin CRL35, the residues 16
      to 43. The separate peptides showed no activity when combined. On one hand, the
      28-mer peptide displayed an unpredicted antimicrobial activity. On the other, 15-
      mer peptide had no consistent anti-Listeria effect. The dissociation constants
      calculated from experimental data indicated that all peptides could bind at
      similar extent to the sensitive cells. However, transmembrane electrical
      potential was not dissipated to the same level by the different peptides; whereas
      the full-length and the C-terminal 28-mer fragment induced almost full
      dissipation, 15-mer fragment produced only a slow and incomplete effect.
      Furthermore, a different interaction of each peptide with membranes was
      demonstrated based on studies carried out with liposomes, which led us to
      conclude that activity was related to structure rather than to net positive
      charges. These results open up the possibility of designing new peptides based on
      the 28-mer fragment with enhanced activity, which would represent a promising
      approach for combating Listeria and other pathogens. 

PMID- 25962067
TI  - Cognitive Improvement after Mild Traumatic Brain Injury Measured with Functional
      Neuroimaging during the Acute Period.
AB  - Functional neuroimaging studies in mild traumatic brain injury (mTBI) have been
      largely limited to patients with persistent post-concussive symptoms, utilizing
      images obtained months to years after the actual head trauma. We sought to
      distinguish acute and delayed effects of mild traumatic brain injury on working
      memory functional brain activation patterns < 72 hours after mild traumatic brain
      injury (mTBI) and again one-week later. We hypothesized that clinical and fMRI
      measures of working memory would be abnormal in symptomatic mTBI patients
      assessed < 72 hours after injury, with most patients showing clinical recovery
      (i.e., improvement in these measures) within 1 week after the initial assessment.
      We also hypothesized that increased memory workload at 1 week following injury
      would expose different cortical activation patterns in mTBI patients with
      persistent post-concussive symptoms, compared to those with full clinical
      recovery. We performed a prospective, cohort study of working memory in emergency
      department patients with isolated head injury and clinical diagnosis of
      concussion, compared to control subjects (both uninjured volunteers and emergency
      department patients with extremity injuries and no head trauma). The primary
      outcome of cognitive recovery was defined as resolution of reported cognitive
      impairment and quantified by scoring the subject's reported cognitive post
      concussive symptoms at 1 week. Secondary outcomes included additional post
      concussive symptoms and neurocognitive testing results. We enrolled 46 subjects:
      27 with mild TBI and 19 controls. The time of initial neuroimaging was 48 (+22
      S.D.) hours after injury (time 1). At follow up (8.7, + 1.2 S.D., days after
      injury, time 2), 18 of mTBI subjects (64%) reported moderate to complete
      cognitive recovery, 8 of whom fully recovered between initial and follow-up
      imaging. fMRI changes from time 1 to time 2 showed an increase in posterior
      cingulate activation in the mTBI subjects compared to controls. Increases in
      activation were greater in those mTBI subjects without cognitive recovery. As
      workload increased in mTBI subjects, activation increased in cortical regions in
      the right hemisphere. In summary, we found neuroimaging evidence for working
      memory deficits during the first week following mild traumatic brain injury.
      Subjects with persistent cognitive symptoms after mTBI had increased requirement
      for posterior cingulate activation to complete memory tasks at 1 week following a
      brain injury. These results provide insight into functional activation patterns
      during initial recovery from mTBI and expose the regional activation networks
      that may be involved in working memory deficits. 

PMID- 25962068
TI  - Ten-Year Follow-up of Patients with Epidemic Post Infectious Glomerulonephritis.
AB  - BACKGROUND: Scarce information on outcomes of epidemic post infectious
      glomerulonephritis is available. This is a 10-year follow-up of the patients that
      developed acute glomerulonephritis in an epidemic outbreak caused by group C
      Streptococcus zooepidemicus in Brazil in 1998, that were also previously
      evaluated 2 and 5 years after the acute episode. METHODS: In this prospective
      study 60 cases (out of 134 in 1998) were reevaluated after 10 years, as well as
      community controls matched by gender and age. They underwent clinical and renal
      function evaluation, including serum creatinine and cystatin C, estimated
      glomerular filtration rate (eGFR), albuminuria and hematuria. RESULTS:
      Comparisons of clinical and renal function aspects of 60 patients and 48
      community controls have not shown significant differences (eGFR <60 ml/min/1.73
      m2 and/or albuminuria >30 mg/g creatinine: 13.8% vs. 12.2%, respectively, p =
      0.817) except for a higher frequency of hypertension in the cases (45.0% vs.
      20.8%, p = 0.009). Comparing the same patients affected in the acute episode, 2,
      5 and 10 years later, it was observed an improvement of median eGFR levels at 2
      years and a trend toward subsequent stabilization in these levels, associated
      with decrease in albuminuria and increased hypertension rates in the last survey.
      At 10 years it was not observed additional reduction of renal function using
      serum creatinine, eGFR and cystatin C. CONCLUSIONS: During the acute episode of
      epidemic GN a considerable proportion of patients presented hypertension and
      reduced renal function; after 2 years and particularly at this 10-year follow-up
      survey there was no worsening of renal function parameters, except for persistent
      higher frequency of hypertension. Nevertheless, a longer follow up is necessary
      to confirm that progressive loss of renal function will not occur.

PMID- 25962069
TI  - A Clinical Predictor Score for 30-Day Mortality among HIV-Infected Adults
      Hospitalized with Pneumonia in Uganda.
AB  - BACKGROUND: Pneumonia is a major cause of mortality among HIV-infected patients.
      Pneumonia severity scores are promising tools to assist clinicians in predicting
      patients' 30-day mortality, but existing scores were developed in populations
      infected with neither HIV nor tuberculosis (TB) and include laboratory data that
      may not be available in resource-limited settings. The objective of this study
      was to develop a score to predict mortality in HIV-infected adults with pneumonia
      in TB-endemic, resource-limited settings. METHODS: We conducted a secondary
      analysis of data from a prospective study enrolling HIV-infected adults with
      cough >=2 weeks and <6 months and clinically suspected pneumonia admitted to
      Mulago Hospital in Kampala, Uganda from September 2008 to March 2011. Patients
      provided two sputum specimens for mycobacteria, and those with Ziehl-Neelsen
      sputum smears that were negative for mycobacteria underwent bronchoscopy with
      inspection for Kaposi sarcoma and testing for mycobacteria and fungi, including
      Pneumocystis jirovecii. A multivariable best subsets regression model was
      developed, and one point was assigned to each variable in the model to develop a
      clinical predictor score for 30-day mortality. RESULTS: Overall, 835 patients
      were studied (mean age 34 years, 53.4% female, 30-day mortality 18.2%). A four
      point clinical predictor score was identified and included heart rate >120
      beats/minute, respiratory rate >30 breaths/minute, oxygen saturation <90%, and
      CD4 cell count <50 cells/mm3. Patients' 30-day mortality, stratified by score,
      was: score 0 or 1, 12.6%, score 2 or 3, 23.4%, score 4, 53.9%. For each 1 point
      change in clinical predictor score, the odds of 30-day mortality increased by 65%
      (OR 1.65, 95% CI 1.39-1.96, p <0.001). CONCLUSIONS: A simple, four-point scoring
      system can stratify patients by levels of risk for mortality. Rapid
      identification of higher risk patients combined with provision of timely and
      appropriate treatment may improve clinical outcomes. This predictor score should
      be validated in other resource-limited settings.

PMID- 25962071
TI  - Trichostatin A rescues the disrupted imprinting induced by somatic cell nuclear
      transfer in pigs.
AB  - Imprinting disorders induced by somatic cell nuclear transfer (SCNT) usually lead
      to the abnormalities of cloned animals and low cloning efficiency. Histone
      deacetylase inhibitors have been shown to improve gene expression, genomic
      methylation reprogramming and the development of cloned embryos, however, the
      imprinting statuses in these treated embryos and during their subsequent
      development remain poorly studied. In this study, we investigated the dynamics of
      H19/Igf2 methylation and transcription in porcine cloned embryos treated with
      trichostatin A (TSA), and examined H19/Igf2 imprinting patterns in cloned fetuses
      and piglets. Our results showed that compared with the maintenance of H19/Igf2
      methylation in fertilized embryos, cloned embryos displayed aberrant H19/Igf2
      methylation and lower H19/Igf2 transcripts. When TSA enhanced the development of
      cloned embryos, the disrupted H19/Igf2 imprinting was largely rescued in these
      treated embryos, more similar to those detected in fertilized counterparts.
      Further studies displayed that TSA effectively rescued the disrupted imprinting
      of H19/Igf2 in cloned fetuses and piglets, prevented the occurrence of cloned
      fetus and piglet abnormalities, and enhanced the full-term development of cloned
      embryos. In conclusion, our results demonstrated that aberrant imprinting induced
      by SCNT led to the abnormalities of cloned fetuses and piglets and low cloning
      efficiency, and TSA rescued the disrupted imprinting in cloned embryos, fetuses
      and piglets, and prevented the occurrence of cloned fetus and piglet
      abnormalities, thereby improving the development of cloned embryos. This study
      would have important implications in improving cloning efficiency and the health
      of cloned animals. 

PMID- 25962072
TI  - Upregulation of NLRP3 Inflammasome in the Tears and Ocular Surface of Dry Eye
      Patients.
AB  - PURPOSE: To evaluate the mRNA and protein expressions of NLRP3 inflammasome and
      its downstream inflammatory factors in human dry eye. METHODS: We recruited 54
      patients with Sjogren's syndrome dry eye (SSDE), 50 patients with non-Sjogren's
      syndrome dry eye (NSSDE), and 46 healthy controls. Tear film breakup time (TBUT),
      Schirmer I test, and fluorescein staining (FL) were performed on all subjects.
      Tear samples were obtained to analyze the inflammatory cytokine levels of IL
      1beta and IL-18 via enzyme-linked immunosorbent (ELISA). Conjunctival impression
      cytology (CIC) specimens were collected to detect the mRNA expression of NLRP3,
      caspase-1, IL-1beta, and IL-18 using quantitative RT-PCR, and the protein
      expression of NLRP3 and caspase-1 by Western blotting. RESULTS: NLRP3 mRNA
      expression showed higher levels in both dry eye groups compared with controls,
      with a comparably significant elevation in the SSDE group (relative 2.47-fold
      upregulation, p<0.05). NLRP3 protein expression was also increased in SSDE group
      (relative1.94-fold upregulation) compared with the controls. mRNA expression of
      caspase-1 was significantly upregulated in both SSDE (relative 1.44-fold
      upregulation, p<0.05) and NSSDE (relative 1.32-fold upregulation, p<0.05).
      Procaspase-1 protein level was increased in SSDE (relative 1.84-fold
      upregulation) and NSSDE (relative 1.12-fold upregulation) versus controls; and
      caspase-1 protein expression was also increased in SSDE (relative 1.49-fold
      upregulation) and NSSDE (relative 1.17-fold upregulation) compared with the
      controls. The patients with SSDE and NSSDE had higher IL-1beta and IL-18 mRNA
      values and protein expressions than the controls did. The relative mRNA
      expression of IL-1beta upregulated 3.59-fold (p<0.001) in SSDE and 2.13-fold
      (p<0.01) in NSSDE compared with the controls. IL-1beta protein level also showed
      significant upregulation in SSDE (p=0.01; vs. controls groups). IL-18 mRNA
      expression levels were significantly upregulated in the SSDE (relative 2.97-fold
      upregulation, p=0.001) and NSSDE (relative 2.05-fold upregulation, p=0.001)
      groups compared with the controls; tear IL-18 concentrations were also
      significantly increased in the SSDE (p<0.001) and NSSDE (p<0.05) groups.
      CONCLUSIONS: In the current study, we found that mRNA and protein expressions of
      NLRP3 inflammasome were upregulated in human dry eyes, especially in SSDE; the
      downstream inflammatory factors caspase-1, IL-1beta, and IL-18 were also elevated
      in dry eye patients. These observations suggest the involvement of NLRP3
      inflammasome in the onset and development of the inflammation in dry eye.

PMID- 25962070
TI  - Effects of mood inductions by meal ambiance and moderate alcohol consumption on
      endocannabinoids and N-acylethanolamines in humans: a randomized crossover trial.
AB  - BACKGROUND: The endocannabinoid system is suggested to play a regulatory role in
      mood. However, the response of circulating endocannabinoids (ECs) to mood changes
      has never been tested in humans. In the present study, we examined the effects of
      mood changes induced by ambiance and moderate alcohol consumption on plasma ECs 2
      arachidonoylglycerol (2-AG), anandamide (AEA), and some N-acylethanolamine (NAE)
      congeners in humans. METHODS: Healthy women (n = 28) participated in a randomized
      cross-over study. They consumed sparkling white wine (340 mL; 30 g alcohol) or
      alcohol-free sparkling white wine (340 mL; <2 g alcohol) as part of a standard
      evening meal in a room with either a pleasant or an unpleasant ambiance. RESULTS:
      Plasma concentrations of palmitoylethanolamide (PEA) and stearoylethanolamide
      (SEA) increased after 30 min in the unpleasant ambiance, while they decreased in
      the pleasant ambiance. Changes in ECs and their NAE congeners correlated with
      mood states, such as happiness and fatigue, but in the pleasant ambiance without
      alcohol only. ECs and their NAE congeners were correlated with serum free fatty
      acids and cortisol. CONCLUSION: This is the first human study to demonstrate that
      plasma NAEs are responsive to an unpleasant meal ambiance. Furthermore,
      associations between mood states and ECs and their NAE congeners were observed.
      TRIAL REGISTRATION: Clinicaltrials.gov NCT01426022.

PMID- 25962074
TI  - Recalls of cardiac implants in the last decade: what lessons can we learn?
AB  - BACKGROUND: Due to an ageing population and demographic changes worldwide, a
      higher prevalence of heart disease is forecasted, which causes an even higher
      demand for cardiac implants in future. The increasing high incidence of clinical
      adverse events attributed especially to high-risk medical devices has led an
      advocated change from many stakeholders. This holds especially true for devices
      like cardiac implants, with their high-risk nature and high complication rates
      associated with considerable mortality, due to their frequent use in older
      populations with frequent co-morbidities. To ensure patients' safety, the
      objective of this study is to analyze different cardiac implants recall reasons
      and different recall systems, based on an overview of the recalls of cardiac
      implant medical devices in the last decade. On the basis of the results from this
      structured analysis, this study provides recommendations on how to avoid such
      recalls from a manufacturer perspective, as well as how to timely react to an
      adverse event from a post-surveillance system perspective. METHODS AND FINDINGS:
      A systematic search of cardiac implant recalls information has been performed in
      the PubMed, ScienceDirect and Scopus databases, as well as data sources in
      regulatory authorities from 193 UN Member States. Data has been extracted for the
      years 2004-2014 with the following criteria applied: cardiac implant medical
      device recalls and reasons for recall, associated harm or risk to patients. From
      the data sources described above, eleven regulatory authorities and 103 recall
      reports have been included in this study. The largest cardiac implant categories
      include ICDs 40.8%, pacemakers 14.5% and stents 14.5%. Regarding the recall
      reasons, the majority of reports were related to device battery problems (33.0%)
      and incorrect therapy delivery (31.1%). From a total of 103 recall reports, five
      reported death and serious injuries. Our review highlights weaknesses in the
      current cardiac implant recall system, including data reporting and management
      issues and provides recommendations for the improvement of safety information and
      management. CONCLUSION: Due to the mortality associated with the nature of
      cardiac implants, the traceability and transparency of safety hazards information
      is crucial. By a structured analysis of recall reasons and their efficient
      management, important knowledge is gained to inform an effective safety-reporting
      system for monitoring the safety of cardiac implanted patients, ideally by
      building up cardiac implant registries worldwide in the future.

PMID- 25962073
TI  - Small Heat Shock Protein Beta-1 (HSPB1) Is Upregulated and Regulates Autophagy
      and Apoptosis of Renal Tubular Cells in Acute Kidney Injury.
AB  - BACKGROUND: Heat shock protein beta-1 (HSPB1, also known as HSP27) is a small
      heat shock protein involved in many cellular processes and reportedly protects
      cells against oxidative stress. Autophagy protects cells from many types of
      stress and is thought to play a key role in preventing stress in acute kidney
      injury (AKI). However, little is known about the role of HSPB1 in autophagy and
      apoptosis in the pathogenesis of AKI. METHODS: We used a rat ischemia/reperfusion
      AKI model and cultured renal tubular cells as an in vitro model. To elucidate the
      regulation of HSPB1, we evaluated the promoter activity and expression of HSPB1
      in normal rat kidney (NRK)-52E cells in the presence of H2O2. To examine the
      regulation of autophagy by HSPB1, we established NRK-light chain 3 (NRK-LC3)
      cells that were stably transfected with a fusion protein of green fluorescent
      protein and LC3. RESULTS: The results of immunohistological examination showed
      that HSPB1 was expressed in proximal tubule cells after AKI. Real-time
      quantitative reverse transcription-polymerase chain reaction and western blot
      analysis showed that HSPB1 messenger RNA and protein expression were upregulated
      6-72 h and 12-72 h, respectively, after ischemia/reperfusion injury. HSPB1
      promoter activity as well as messenger RNA and protein expression indicated dose
      dependent induction by H2O2. HSPB1 overexpression-induced autophagy in NRK-LC3
      cells under normoxic conditions was confirmed with confocal microscopy, which
      revealed the presence of LC3-positive granules. Furthermore, H2O2-induced
      autophagy was inhibited by the transfection of small interfering RNAs for HSPB1.
      Overexpression of HSPB1 reduced BAX activation and H2O2-induced apoptosis, as
      measured by caspase 3 activity and terminal deoxynucleotidyl transferase
      deoxyuridine triphosphate nick end labeling assay. CONCLUSIONS: We showed that
      HSPB1 expression increased during oxidative stress in AKI. Incremental HSPB1
      expression increased autophagic flux and inhibited apoptosis in renal tubular
      cells. These results indicate that HSPB1 upregulation plays a role in the
      pathophysiology of AKI.

PMID- 25962077
TI  - Correction: Gentamicin-Attenuated Leishmania infantum Vaccine: Protection of Dogs
      against Canine Visceral Leishmaniosis in Endemic Area of Southeast of Iran.

PMID- 25962076
TI  - Small RNA Profiling of Two Important Cultivars of Banana and Overexpression of
      miRNA156 in Transgenic Banana Plants.
AB  - Micro RNAs (miRNAs) are a class of non-coding, short RNAs having important roles
      in regulation of gene expression. Although plant miRNAs have been studied in
      detail in some model plants, less is known about these miRNAs in important fruit
      plants like banana. miRNAs have pivotal roles in plant growth and development,
      and in responses to diverse biotic and abiotic stress stimuli. Here, we have
      analyzed the small RNA expression profiles of two different economically
      significant banana cultivars by using high-throughput sequencing technology. We
      identified a total of 170 and 244 miRNAs in the two libraries respectively
      derived from cv. Grand Naine and cv. Rasthali leaves. In addition, several
      cultivar specific microRNAs along with their putative target transcripts were
      also detected in our studies. To validate our findings regarding the small RNA
      profiles, we also undertook overexpression of a common microRNA, MusamiRNA156 in
      transgenic banana plants. The transgenic plants overexpressing the stem-loop
      sequence derived from MusamiRNA156 gene were stunted in their growth together
      with peculiar changes in leaf anatomy. These results provide a foundation for
      further investigations into important physiological and metabolic pathways
      operational in banana in general and cultivar specific traits in particular. 

PMID- 25962075
TI  - Beyond the biomedical: community resources for mental health care in rural
      Ethiopia.
AB  - BACKGROUND: The focus of discussion in addressing the treatment gap is often on
      biomedical services. However, community resources can benefit health service
      scale-up in resource-constrained settings. These assets can be captured
      systematically through resource mapping, a method used in social action research.
      Resource mapping can be informative in developing complex mental health
      interventions, particularly in settings with limited formal mental health
      resources. METHOD: We employed resource mapping within the Programme for
      Improving Mental Health Care (PRIME), to systematically gather information on
      community assets that can support integration of mental healthcare into primary
      care in rural Ethiopia. A semi-structured instrument was administered to key
      informants. Community resources were identified for all 58 sub-districts of the
      study district. The potential utility of these resources for the provision of
      mental healthcare in the district was considered. RESULTS: The district is rich
      in community resources: There are over 150 traditional healers, 164 churches and
      mosques, and 401 religious groups. There were on average 5 eddir groups
      (traditional funeral associations) per sub-district. Social associations and 51
      micro-finance institutions were also identified. On average, two traditional bars
      were found in each sub-district. The eight health centres and 58 satellite
      clinics staffed by Health Extension Workers (HEWs) represented all the biomedical
      health services in the district. In addition the Health Development Army (HDA)
      are community volunteers who support health promotion and prevention activities.
      DISCUSSION: The plan for mental healthcare integration in this district was
      informed by the resource mapping. Community and religious leaders, HEWs, and HDA
      may have roles in awareness-raising, detection and referral of people with mental
      illness, improving access to medical care, supporting treatment adherence, and
      protecting human rights. The diversity of community structures will be used to
      support rehabilitation and social reintegration. Alcohol use was identified as a
      target disorder for community-level intervention.

PMID- 25962078
TI  - Postoperative Critical Care of the Adult Cardiac Surgical Patient. Part I:
      Routine Postoperative Care.
AB  - OBJECTIVES: Cardiac surgery, including coronary artery bypass, cardiac valve, and
      aortic procedures, is among the most common surgical procedures performed in the
      United States. Successful outcomes after cardiac surgery depend on optimum
      postoperative critical care. The cardiac intensivist must have a comprehensive
      understanding of cardiopulmonary physiology and the sequelae of cardiopulmonary
      bypass. In this concise review, targeted at intensivists and surgeons, we discuss
      the routine management of the postoperative cardiac surgical patient. DATA SOURCE
      AND SYNTHESIS: Narrative review of relevant English-language peer-reviewed
      medical literature. CONCLUSIONS: Critical care of the cardiac surgical patient is
      a complex and dynamic endeavor. Adequate fluid resuscitation, appropriate
      inotropic support, attention to rewarming, and ventilator management are key
      components. Patient safety is enhanced by experienced personnel, a structured
      handover between the operating room and ICU teams, and appropriate transfusion
      strategies.

PMID- 25962079
TI  - Five-Year Survival of Children With Chronic Critical Illness in Australia and New
      Zealand.
AB  - OBJECTIVE: Outcomes for children with chronic critical illness are not defined.
      We examined the long-term survival of these children in Australia and New
      Zealand. DESIGN: All cases of PICU chronic critical illness with length of stay
      more than 28 days and age 16 years old or younger in Australia and New Zealand
      from 2000 to 2011 were studied. Five-year survival was analyzed using Kaplan-Meir
      estimates, and risk factors for mortality evaluated using Cox regression.
      SETTING: All PICUs in Australia and New Zealand. PATIENTS: Nine hundred twenty
      four children with chronic critical illness. INTERVENTION: None. MEASUREMENTS AND
      MAIN RESULTS: Nine hundred twenty-four children were admitted to PICU for longer
      than 28 days on 1,056 occasions, accounting for 1.3% of total admissions and
      23.5% of bed days. Survival was known for 883 of 924 patients (95.5%), with a
      median follow-up of 3.4 years. The proportion with primary cardiac diagnosis
      increased from 27% in 2000-2001 to 41% in 2010-2011. Survival was 81.4% (95% CI,
      78.6-83.9) to PICU discharge, 70% (95% CI, 66.7-72.8) at 1 year, and 65.5% (95%
      CI, 62.1-68.6) at 5 years. Five-year survival was 64% (95% CI, 58.7-68.6) for
      children admitted in 2000-2005 and 66% (95% CI, 61.7-70) if admitted in 2006-2011
      (log-rank test, p = 0.37). After adjusting for admission severity of illness
      using the Paediatric Index of Mortality 2 score, predictors for 5-year mortality
      included bone marrow transplant (hazard ratio, 3.66; 95% CI, 2.26-5.92) and
      single-ventricle physiology (hazard ratio, 1.98; 95% CI, 1.37-2.87). Five-year
      survival for single-ventricle physiology was 47.2% (95% CI, 34.3-59.1) and for
      bone marrow transplantation 22.8% (95% CI, 8.7-40.8). CONCLUSIONS: Two thirds of
      children with chronic critical illness survive for at-least 5 years, but there
      was no improvement between 2000 and 2011. Cardiac disease constitutes an
      increasing proportion of pediatric chronic critical illness. Bone marrow
      transplant recipients and single-ventricle physiology have the poorest outcomes.

PMID- 25962080
TI  - beta1-Adrenergic Inhibition Improves Cardiac and Vascular Function in
      Experimental Septic Shock.
AB  - OBJECTIVE: Preliminary experimental data suggest that selective beta1-blockers
      may improve ex vivo cardiac function in animal sepsis. Currently, the effects of
      esmolol on in vivo cardiac function and on vascular function are unknown. The
      present study was designed to examine the effects of the beta1-selective blocker
      esmolol on myocardial and vascular function in peritonitis-induced septic rats
      and to explore the inflammatory pathways involved in this process. DESIGN:
      Randomized animal study. SETTING: University research laboratory. SUBJECTS: Male
      Wistar rats. INTERVENTIONS: Four hours after cecal ligation and puncture, Wistar
      rats were randomly allocated to the following groups: control, esmolol,
      norepinephrine (started at 18 hr after the surgery), and esmolol (started at 4 hr
      after the surgery) + norepinephrine (started at 18 hr after the surgery).
      Assessment at 18 hours after surgery was focused on cardiac contractility and
      vascular ex vivo function. Cardiac and vascular protein expressions of nuclear
      factor kappaB and endothelial nitric oxide synthase/Akt/inducible nitric oxide
      synthase pathways were assessed by Western blotting. MEASUREMENTS AND MAIN
      RESULTS: When compared with sham-operated animals, cecal ligation and puncture
      animals developed hypotension, cardiac depression, and vascular
      hyporesponsiveness to vasopressor treatment. Esmolol infusion increased cardiac
      contractility and restored mesenteric vasoreactivity. This effect was associated
      with a decrease in nuclear factor kappaB activation, an increase in Akt and
      endothelial nitric oxide synthase phosphorylation, and a decrease in inducible
      nitric oxide synthase expression both at the cardiac and vessel level. Esmolol
      infusion was also associated with an up-regulation in alpha1-vascular
      adrenoreceptors. CONCLUSION: Adjunction of selective beta1-blockade to standard
      septic shock management enhances intrinsic cardiac contractility and vascular
      responsiveness to catecholamines. These protective cardiovascular effects are
      likely predominantly attributed to the anti-inflammatory effect of esmolol.

PMID- 25962081
TI  - Persistence of Neuropsychological Deficits Following Pediatric Critical Illness.
AB  - OBJECTIVE: To study 12-month persistence of neuropsychological deficits in PICU
      survivors. DESIGN: Prospective follow-up study. SETTING: Two PICUs. PARTICIPANTS:
      Children 5-16 years old with neuropsychological deficits 3-6 months following
      PICU care for meningoencephalitis, sepsis, and other critical illnesses
      (excluding other primary neurological disorders). INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Neuropsychological function was assessed using the
      Cambridge Neuropsychological Test Automated Battery, the Children's Memory Scale,
      and the Wechsler Abbreviated Scale of Intelligence or Wide Range Intelligence
      Test. Forty-seven of 88 PICU admitted children (53%) were identified as
      neuropsychologically impaired 3-6 months after discharge; of these, 23 provided
      12-month follow-up data. In spite of significant improvements in measures of
      memory, there was little change in intelligence quotient and visual attention
      over the study period, and children's educational progress remained below
      expectation. CONCLUSIONS: We found persistently reduced neuropsychological
      function following PICU admission in the critical illnesses under study.

PMID- 25962082
TI  - Lactate Testing in Suspected Sepsis: Trends and Predictors of Failure to Measure
      Levels.
AB  - OBJECTIVES: Serum lactate monitoring is central to risk stratification and
      management of sepsis and is now part of a potential quality measure. We examined
      11-year trends in lactate testing and predictors of failure to measure lactates
      in patients with severe sepsis. DESIGN: Retrospective cohort study. SETTING: Two
      U.S. academic hospitals. PATIENTS: Adult patients admitted from 2003 to 2013.
      INTERVENTIONS: Annual rates of lactate measurement were assessed in patients who
      had blood cultures ordered and patients with severe sepsis, as defined by
      concomitant International Classification of Diseases, Ninth Revision codes for
      infection and organ dysfunction. The approximate time of suspected sepsis was
      determined by the first blood culture order with concurrent antibiotic
      initiation. Multivariate analysis was performed to identify predictors of failure
      to measure lactates in severe sepsis cases in 2013. MEASUREMENTS AND MAIN
      RESULTS: Among hospitalizations with blood culture orders, rates of lactate
      measurement increased from 11% in 2003 to 48% in 2013 (p < 0.001 for linear
      trend). Rates of repeat lactate measurement within 6 hours after lactate levels
      greater than or equal to 4.0 mmol/L increased from 23% to 69% (p < 0.001).
      Patients were progressively less likely to be on vasopressors at the time of
      first lactate measurement (49% in 2003 vs 21% in 2013; p < 0.001). Despite these
      trends, lactates were measured at the time of suspected sepsis in only 65% of
      patients with severe sepsis in 2013. On multivariate analysis, hospital-onset
      sepsis and hospitalization on a nonmedical service were significant predictors of
      failure to measure lactates (adjusted odds ratio, 7.56; 95% CI, 6.31-9.06 and
      adjusted odds ratio, 2.08; 95% CI, 1.76-2.24, respectively). CONCLUSIONS: Lactate
      testing has increased dramatically over time and is being extended to patients
      without overt shock. However, rates of serial lactate testing are still
      suboptimal, and lactates are not being measured in many patients with severe
      sepsis. Hospital-onset sepsis and nonmedical units may be high-yield targets for
      quality improvement initiatives.

PMID- 25962083
TI  - A Multibiomarker-Based Model for Estimating the Risk of Septic Acute Kidney
      Injury.
AB  - OBJECTIVE: The development of acute kidney injury in patients with sepsis is
      associated with worse outcomes. Identifying those at risk for septic acute kidney
      injury could help to inform clinical decision making. We derived and tested a
      multibiomarker-based model to estimate the risk of septic acute kidney injury in
      children with septic shock. DESIGN: Candidate serum protein septic acute kidney
      injury biomarkers were identified from previous transcriptomic studies. Model
      derivation involved measuring these biomarkers in serum samples from 241 subjects
      with septic shock obtained during the first 24 hours of admission and then using
      a Classification and Regression Tree approach to estimate the probability of
      septic acute kidney injury 3 days after the onset of septic shock, defined as at
      least two-fold increase from baseline serum creatinine. The model was then tested
      in a separate cohort of 200 subjects. SETTING: Multiple PICUs in the United
      States. INTERVENTIONS: None other than standard care. MEASUREMENTS AND MAIN
      RESULTS: The decision tree included a first-level decision node based on day 1
      septic acute kidney injury status and five subsequent biomarker-based decision
      nodes. The area under the curve for the tree was 0.95 (CI95, 0.91-0.99), with a
      sensitivity of 93% and a specificity of 88%. The tree was superior to day 1
      septic acute kidney injury status alone for estimating day 3 septic acute kidney
      injury risk. In the test cohort, the tree had an area under the curve of 0.83
      (0.72-0.95), with a sensitivity of 85% and a specificity of 77% and was also
      superior to day 1 septic acute kidney injury status alone for estimating day 3
      septic acute kidney injury risk. CONCLUSIONS: We have derived and tested a model
      to estimate the risk of septic acute kidney injury on day 3 of septic shock using
      a novel panel of biomarkers. The model had very good performance in a test cohort
      and has test characteristics supporting clinical utility and further prospective
      evaluation.

PMID- 25962085
TI  - Long-term menopausal hormone therapy and health consequences - how to choose
      sides?
AB  - There is no debate any more on the good safety profile of postmenopausal hormone
      therapy (HT) in healthy perimenopausal and early postmenopausal women, but there
      are still many open issues related to the consequences of long-term HT,
      especially in older women. A recent Cochrane meta-analysis showed that women who
      started HT less than 10 years after the menopause had lower mortality and
      coronary heart disease (CHD), but more venous thromboembolism (DVT). However, in
      those who started treatment more than 10 years after the menopause, there was
      high-quality evidence that it had little effect on death or CHD between HT and
      placebo groups but there was an increased risk of stroke and DVT. In contrast,
      many large, observational studies such as a recent one from Finland (3.3 million
      years of HT exposure) have shown that the risk of CHD or stroke death and all
      cause mortality was significantly reduced, both in those who initiated HT below
      or above age 60 years. Because of conflicting data concerning long-term HT use,
      it seems that every health-care provider chooses as reference those studies that
      can support his/her individual views and therapeutic approach. 

PMID- 25962084
TI  - Transient and Persistent Acute Kidney Injury and the Risk of Hospital Mortality
      in Critically Ill Patients: Results of a Multicenter Cohort Study.
AB  - OBJECTIVE: To assess the prognostic impact of transient and persistent acute
      kidney injury in critically ill patients. DESIGN: Retrospective analysis of
      prospectively collected patient data SETTING: : Six hospital ICUs. PATIENTS:
      Critically-ill patients with ICU stay longer than three days. INTERVENTION: None.
      MEASUREMENTS AND MAIN RESULTS: Assessment of hospital survival with respect to
      acute kidney injury duration. A total of 447 patients were included in this
      study, including 283 patients (63.3%) with an acute kidney injury at admission
      (175 and 108 patients with persistent and transient acute kidney injury,
      respectively). Patients with persistent acute kidney injury more frequently had
      stage 3 acute kidney injury (42.9% vs 30.6%; p = 0.04). Hospital survival was
      76.2% (n = 125) in patients without acute kidney injury, 70.4% (n = 76) in
      patients with transient acute kidney injury, and 61.1% (n = 107) in patients with
      persistent acute kidney injury. After adjustment for confounding factors, the
      factors associated with lower hospital survival were the need for vasopressors
      (odds ratio, 0.65; 95% CI, 0.43-0.98) and the presence of persistent acute kidney
      injury (odds ratio, 0.58; 95% CI, 0.36-0.95). When included in the final model,
      stage 3 acute kidney injury was independently associated with a lower hospital
      survival (odds ratio, 0.83; 95% CI, 0.70-0.98), and persistent acute kidney
      injury was no longer associated with outcome. CONCLUSION: Two thirds of the
      critically ill patients with acute kidney injury have persistent acute kidney
      injury. Although mortality increased progressively with the duration of acute
      kidney injury, we found no independent association between this duration and
      patient outcome when the acute kidney injury severity is taken into account. Our
      results suggest that the classical "prerenal acute kidney injury" and "acute
      tubular necrosis" paradigm might be of limited interest from a pathophysiological
      or prognostic point of view.

PMID- 25962086
TI  - Tracing engineered nanomaterials in biological tissues using coherent anti-Stokes
      Raman scattering (CARS) microscopy - A critical review.
AB  - Nanomaterials (NMs) are used in an extremely diverse range of products and are
      increasingly entering the environment, driving a need to better understand their
      potential health effects in both humans and wildlife. A major challenge in
      nanoparticle (eco)toxicology is the ability to localise NMs post exposure, to
      enable more targeted biological effects analyses. A range of imaging techniques
      have been applied to do so, but they are limited, requiring either extensive
      processing of the material, staining or use of high intensity illumination that
      can lead to photo damage and/or have limited tissue penetration. Coherent anti
      Stokes Raman scattering (CARS) microscopy is a label-free imaging technique,
      providing contrast based on the intrinsic molecular vibrations of a specimen,
      circumventing the need for chemical perturbation by exogenous labels. CARS uses
      near infra-red excitation wavelengths which allow microscopy at depths of several
      hundred microns in intact tissues and minimises photo-damage to live and delicate
      samples. Here we provide an overview of the CARS process and present a series of
      illustrative examples demonstrating its application for detecting NMs within
      biological tissues, ranging from isolated cells to whole organisms and including
      materials spanning metals to polymers. We highlight the advantages of this
      technique which include chemically selective live imaging and substantial depth
      penetration, but we also discuss its limitations when applied to nanotoxicology,
      which most notably include the lack of resolution for studies on single
      nanoparticles. 

PMID- 25962087
TI  - Cross-reactive and pre-existing antibodies to therapeutic antibodies--Effects on
      treatment and immunogenicity.
AB  - The potential for immunogenicity is an ever-present concern during the
      development of biopharmaceuticals. Therapeutic antibodies occasionally elicit an
      antibody response in patients, which can result in loss of response or adverse
      effects. However, antibodies that bind a drug are sometimes found in pre
      treatment serum samples, with the amount depending on drug, assay, and patient
      population. This review summarizes published data on pre-existing antibodies to
      therapeutic antibodies, including rheumatoid factors, anti-allotype antibodies,
      anti-hinge antibodies, and anti-glycan antibodies. Unlike anti-idiotype
      antibodies elicited by the drug, pre-formed antibodies in general appear to have
      little consequences during treatment. In the few cases where (potential) clinical
      consequences were encountered, antibodies were characterized and found to bind a
      distinct, unusual epitope of the therapeutic. Immunogenicity testing strategies
      should therefore always include a proper level of antibody characterization,
      especially when pre-formed antibodies are present. This minimizes false
      positives, particularly due to rheumatoid factors, and helps to judge the
      potential threat in case a genuine pre-dose antibody reactivity is identified. 

PMID- 25962088
TI  - Transmitted Drug Resistance Mutations in Antiretroviral-Naive Injection Drug
      Users with Chronic HIV-1 Infection in Iran.
AB  - The growing incidence and transmission of drug resistant HIV-1 strains due to
      widespread use of antiretroviral therapy (ART) can jeopardize the success of
      first-line ART. While there is a known moderate prevalence of transmitted drug
      resistance (TDR) among newly infected Iranians, no data exist about the rate of
      these primary resistance mutations among the ART-naive, chronically infected
      individuals who are, in fact, the main candidates for ART initiation. To address
      this issue, we collected blood samples from 40 ART-naive injection drug-users
      (IDUs) with chronic HIV-1 infection (seroconversion time ranging from 2 to 9
      years) living in Sanandaj, Iran, followed by sequencing of the protease and
      reverse-transcriptase regions from their HIV-1 genome. Phylogenetic analyses of
      the sequenced regions revealed that all samples were CRF35_AD. Transmitted
      resistance mutations were interpreted as surveillance drug-resistant mutations
      (SDRMs) based on the world health organization (WHO) algorithm. The frequency of
      SDRMs to any class of antiretroviral drugs was 15%, which included mutations to
      nucleoside reverse transcriptase inhibitors (NRTIs, 10%), with M41L and M184V as
      the most common (5%), and non-nucleoside reverse transcriptase inhibitors
      (NNRTIs, 5%), with K103N as the only detected mutation (5%). Although not in the
      WHO SDRMs list, several minor protease inhibitor resistant mutations listed in
      the International Antiviral Society-USA panel were identified, of which M36I,
      H69K, L89M/V/I (each one 100%) and K20R/T (92.5%) can be considered as
      polymorphic signatures for CRF35_AD.The relatively high rate of TDR mutations in
      our study raises concerns about the risk of treatment failure in chronically
      infected IDUs of Sanandaj city. These results suggest that routine resistance
      testing should be considered before the therapy initiation in this area.
      Additional surveillance studies are required to generalize this deduction to
      other cities of Iran. 

PMID- 25962089
TI  - Epigenetics and miRNA as predictive markers and targets for lung cancer
      chemotherapy.
AB  - Lung cancer cells show inherent and acquired resistance to chemotherapy. The lack
      of good predictive markers/novel targets and the incomplete understanding of the
      mechanisms of resistance limit the success of lung cancer response to
      chemotherapy. In the present study, we used an isogenic pair of lung
      adenocarcinoma cell lines; A549 (wild-type) and A549DOX11 (doxorubicin resistant)
      to study the role of epigenetics and miRNA in resistance/response of non-small
      cell lung cancer (NSCLC) cells to doxorubicin. Our results demonstrate
      differential expression of epigenetic markers whereby the level of HDACs 1, 2, 3
      and4, DNA methyltransferase, acetylated H2B and acetylated H3 were lower in
      A549DOX11 compared to A549 cells. Fourteen miRNAs were dys-regulated in A549DOX11
      cells compared to A549 cells, of these 14 miRNAs, 4 (has-mir-1973, 494, 4286 and
      29b-3p) have shown 2.99 - 4.44 fold increase in their expression. This was
      associated with reduced apoptosis and higher resistance of A549DOX11cells to
      doxorubicin and etoposide. Sequential treatment with the epigenetic modifiers
      trichostatin A or 5-aza-2'-deoxycytidine followed by doxorubicin resulted in: (i)
      enhanced sensitivity of both cell lines to doxorubicin especially at low
      concentrations, (ii) enhanced doxorubicin-induced DNA damage in both cell lines,
      (iii) dysregulation of some miRNAs in A549 cells. In conclusion, A549DOX11 cells
      resistant to DNA damaging drugs have epigenetic profile and miRNA expression
      different from the sensitive cells. Moreover, epigenetic modifiers may reverse
      the resistance of certain NSCLC cells to DNA damaging agents by enhancing
      induction of DNA damage. This may open the door for using epigenetic
      profile/miRNA expression of some cancer cells as resistance markers/targets to
      improve response of resistant cells to doxorubicin and for the use of combination
      doxorubicin/epigenetic modifiers to reduce doxorubicin toxicity. 

PMID- 25962091
TI  - Proceedings from the American Association of Clinical Endocrinologists and
      American College of Endocrinology consensus conference on glucose monitoring.
AB  - This document represents the official position of the American Association of
      Clinical Endocrinologists and the American College of Endocrinology. Where there
      were no randomized controlled trials or specific U.S. FDA labeling for issues in
      clinical practice, the participating clinical experts utilized their judgment and
      experience. Every effort was made to achieve consensus among the committee
      members. Position statements are meant to provide guidance, but they are not to
      be considered prescriptive for any individual patient and cannot replace the
      judgment of a clinician.

PMID- 25962090
TI  - Oxford recovery housing: Length of stay correlated with improved outcomes for
      women previously involved with the criminal justice system.
AB  - BACKGROUND: Housing plays a crucial role in providing resources for and aiding an
      individual's reentry into the community following incarceration and substance use
      treatment. As such, this study examined the influence of recovery homes on a
      sample of former female substance-using women with criminal justice involvement.
      METHODS: Two hundred women who had been involved with the criminal justice system
      within the preceding 2 years were recruited from multiple sites in metropolitan
      Chicago. These women were assigned to either 1 of 2 conditions: Oxford House (OH)
      recovery homes or usual aftercare (UA). RESULTS: Those with longer stays in OH (6
      months or more) had better outcomes in terms of alcohol and drug use, employment,
      and self-efficacy than those with shorter stays. Outcomes for those who stayed in
      OH were not appreciably different than the UA condition on substance use and
      employment, but fewer deaths occurred for those in the OH condition. CONCLUSIONS:
      Findings suggest that length of stay of 6 or more months is critical for those in
      recovery homes, but it is important for us to better understand the processes
      through which longer stays influence better outcomes.

PMID- 25962092
TI  - AACE/ACE disease state clinical review: diagnosis and management of midgut
      carcinoids.
AB  - OBJECTIVE: Neuroendocrine tumors (NETs) are a collection of complex tumors that
      arise from the diffuse endocrine system, primarily from the digestive tract.
      Carcinoid tumors most commonly originate from the small intestine. These tumors
      are either referred to as small intestinal neuroendocrine tumors or midgut
      carcinoids (MGCs). The purpose of this review article is to survey the diagnostic
      and therapeutic pathways for patients with MGC and provide an overview of the
      complex multidisciplinary care involved in improving their quality of life,
      treatment outcomes, and survival. METHODS: The current literature regarding the
      diagnosis and management of MGCs was reviewed. RESULTS: Dry flushing and
      secretory diarrhea are the hallmarks of the clinical syndrome of MGC. Managing
      MGC requires attention to the overall symptom complex, including the physical
      effects of the tumor and biomarker levels. The somatostatin analogs (SAs)
      octreotide and lanreotide are highly efficacious for symptomatic improvement.
      MGCs require resection to encompass the primary tumor and mesenteric lymph node
      metastases and should include cholecystectomy if the patient is likely to receive
      SA therapy. Debulking of liver metastasis by resection in combination with
      ablative therapies and other liver-directed modalities may help palliate symptoms
      and hormonal overproduction in carefully selected patients. Quality of life is an
      important measure of patients' perception of the burden of their disease and
      impact of treatment modalities and may be a useful guide in deciding changes in
      therapy to alter apparent health status. CONCLUSION: MGC is a challenging
      malignancy that requires the input of a multidisciplinary team to develop the
      best treatment plan. Consultation with expert centers that specialize in NETs may
      also be indicated for complex cases. With expert care, patients can be cured or
      live with the disease and enjoy good quality of life.

PMID- 25962094
TI  - Correction.

PMID- 25962093
TI  - AACE/ACE disease state clinical review: pancreatic neuroendocrine incidentalomas.
AB  - Incidental detection of pancreatic neuroendocrine tumors (PNETs) has
      substantially increased over the last decade due to widespread use of advanced
      imaging studies. Reliable initial imaging-based characterization is crucial for
      the differential diagnosis from other exocrine neoplasms and to determine the
      appropriate management plan. Measurements of chromogranin A, pancreatic
      polypeptide, and calcitonin are recommended for the biochemical evaluation. A
      thorough medical history needs to be performed to rule out multiple endocrine
      neoplasia (MEN) type 1. The European Neuroendocrine Tumor Society (ENETS)/Tumor
      Node Metastasis (TNM) staging system together with a grading based on the Ki-67
      proliferation index and mitotic counts has proven to give more appropriate
      prognostic information than the World Health Organization (WHO)/American Joint
      Committee on Cancer (AJCC) TNM staging but may still fail to safely differentiate
      benign from malignant lesions. Poorly differentiated PNETs generally present with
      metastases and are rarely amenable for resection. Well- or intermediately
      differentiated tumors >=2 cm with imaging evidence of malignancy or with a Ki-67
      >2% should be resected. It has been suggested that non-MEN related,
      nonfunctioning, and asymptomatic PNETs <2 cm with a Ki-67 index <=2% carry a low
      risk of metastasis and may be observed in the absence of clinical or radiologic
      criteria of malignancy or progression, especially in older patients. However,
      because metastases may occur with long delay with smaller PNETS, physicians
      should consider patient age, lesion location, and the risks of operation, and
      patients not undergoing surgery need to be closely followed closely.

PMID- 25962095
TI  - Distribution of Thelastomatoid Nematodes (Nematoda: Oxyurida) in Endemic and
      Introduced Cockroaches on the Galapagos Island Archipelago, Ecuador.
AB  - The thelastomatoid pinworm fauna (Nematoda: Oxyurida: Thelastomatoidea) was
      surveyed in 3 endemic species and 6 introduced species of cockroach hosts
      (Insecta: Blattaria) in the Galapagos Islands, Ecuador. A total of 658 host
      specimens were examined from preserved collections that had been collected
      between 1966 and 2003 from 7 islands in the archipelago. Eight species of
      pinworms were identified from these cockroach hosts, including the dominant
      species Cephalobellus ovumglutinosus and a Severianoia sp. as well as Leidynema
      appendiculata, Hammerschmidtiella diesingi, an unidentified Cephalobellus species
      resembling Cephalobellus magalhaesi, an unidentified Protrellus species closely
      resembling Protrellus shamimi, and an undescribed Blattophila sp. Five new host
      records are identified for C. ovumglutinosus including the endemic Galapagos
      cockroaches Chorisoneura carpenteri, Ischnoptera snodgrassii, and Ischnoptera
      santacruzensis. These endemics were also infected with an undescribed Blatticola
      sp. Other species recorded resemble known pinworms from other hosts around the
      world. Prevalence between islands and between host species was variable, but
      total prevalence for individual pinworm species was consistently low (<10%). A
      single host specimen examined was infected with more than 1 pinworm species;
      otherwise only a single species was observed in each infected host. At least 1
      introduced pinworm species carried to the islands via invasive cockroach hosts
      was present in endemic host species, but several globally widespread introduced
      pinworm species were absent from endemic cockroaches. Santa Cruz was inhabited by
      the greatest number of pinworm species, likely due to a higher rate of invasive
      host introduction. This survey, the first from this region, showed that the
      distribution and transmission of pinworms in the Galapagos Islands is complex and
      may provide future models of invertebrate dispersal and speciation in an
      ecosystem already rich with examples of evolution. 

PMID- 25962096
TI  - Molecular Mechanisms of ZnO Nanoparticle Dispersion in Solution: Modeling of
      Surfactant Association, Electrostatic Shielding and Counter Ion Dynamics.
AB  - Molecular models of 5 nm sized ZnO/Zn(OH)2 core-shell nanoparticles in ethanolic
      solution were derived as scale-up models (based on an earlier model created from
      ion-by-ion aggregation and self-organization) and subjected to mechanistic
      analyses of surface stabilization by block-copolymers. The latter comprise a poly
      methacrylate chain accounting for strong surfactant association to the
      nanoparticle by hydrogen bonding and salt-bridges. While dangling poly-ethylene
      oxide chains provide only a limited degree of sterical hindering to nanoparticle
      agglomeration, the key mechanism of surface stabilization is electrostatic
      shielding arising from the acrylates and a halo of Na+ counter ions associated to
      the nanoparticle. Molecular dynamics simulations reveal different solvent shells
      and distance-dependent mobility of ions and solvent molecules. From this, we
      provide a molecular rationale of effective particle size, net charge and
      polarizability of the nanoparticles in solution. 

PMID- 25962098
TI  - Cellular promyelocytic leukemia protein is an important dengue virus restriction
      factor.
AB  - The intrinsic antiviral defense is based on cellular restriction factors that are
      constitutively expressed and, thus, active even before a pathogen enters the
      cell. The promyelocytic leukemia (PML) nuclear bodies (NBs) are discrete nuclear
      foci that contain several cellular proteins involved in intrinsic antiviral
      responses against a number of viruses. Accumulating reports have shown the
      importance of PML as a DNA virus restriction factor and how these pathogens evade
      this antiviral activity. However, very little information is available regarding
      the antiviral role of PML against RNA viruses. Dengue virus (DENV) is an RNA
      emerging mosquito-borne human pathogen affecting millions of individuals each
      year by causing severe and potentially fatal syndromes. Since no licensed
      antiviral drug against DENV infection is currently available, it is of great
      importance to understand the factors mediating intrinsic immunity that may lead
      to the development of new pharmacological agents that can boost their potency and
      thereby lead to treatments for this viral disease. In the present study, we
      investigated the in vitro antiviral role of PML in DENV-2 A549 infected cells. 

PMID- 25962097
TI  - A conserved histidine modulates HSPB5 structure to trigger chaperone activity in
      response to stress-related acidosis.
AB  - Small heat shock proteins (sHSPs) are essential 'holdase' chaperones that form
      large assemblies and respond dynamically to pH and temperature stresses to
      protect client proteins from aggregation. While the alpha-crystallin domain (ACD)
      dimer of sHSPs is the universal building block, how the ACD transmits structural
      changes in response to stress to promote holdase activity is unknown. We found
      that the dimer interface of HSPB5 is destabilized over physiological pHs and a
      conserved histidine (His-104) controls interface stability and oligomer structure
      in response to acidosis. Destabilization by pH or His-104 mutation shifts the ACD
      from dimer to monomer but also results in a large expansion of HSPB5 oligomer
      states. Remarkably, His-104 mutant-destabilized oligomers are efficient holdases
      that reorganize into structurally distinct client-bound complexes. Our data
      support a model for sHSP function wherein cell stress triggers small
      perturbations that alter the ACD building blocks to unleash a cryptic mode of
      chaperone action. 

PMID- 25962099
TI  - Modeling Analysis of Signal Sensitivity and Specificity by Vibrio fischeri LuxR
      Variants.
AB  - The LuxR protein of the bacterium Vibrio fischeri belongs to a family of
      transcriptional activators that underlie pheromone-mediated signaling by
      responding to acyl-homoserine lactones (-HSLs) or related molecules. V. fischeri
      produces two acyl-HSLs, N-3-oxo-hexanoyl-HSL (3OC6-HSL) and N-octanoyl-HSL (C8
      HSL), each of which interact with LuxR to facilitate its binding to a "lux box"
      DNA sequence, thereby enabling LuxR to activate transcription of the lux operon
      responsible for bioluminescence. We have investigated the HSL sensitivity of four
      different variants of V. fischeri LuxR: two derived from wild-type strains ES114
      and MJ1, and two derivatives of LuxRMJ1 generated by directed evolution. For each
      LuxR variant, we measured the bioluminescence induced by combinations of C8-HSL
      and 3OC6-HSL. We fit these data to a model in which the two HSLs compete with
      each other to form multimeric LuxR complexes that directly interact with lux to
      activate bioluminescence. The model reproduces the observed effects of HSL
      combinations on the bioluminescence responses directed by LuxR variants,
      including competition and non-monotonic responses to C8-HSL and 3OC6-HSL. The
      analysis yields robust estimates for the underlying dissociation constants and
      cooperativities (Hill coefficients) of the LuxR-HSL complexes and their
      affinities for the lux box. It also reveals significant differences in the
      affinities of LuxRMJ1 and LuxRES114 for 3OC6-HSL. Further, LuxRMJ1 and LuxRES114
      differed sharply from LuxRs retrieved by directed evolution in the cooperativity
      of LuxR-HSL complex formation and the affinity of these complexes for lux. These
      results show how computational modeling of in vivo experimental data can provide
      insight into the mechanistic consequences of directed evolution. 

PMID- 25962100
TI  - Darunavir/cobicistat once daily for the treatment of HIV.
AB  - A current focus in HIV management is improving adherence by minimizing pill
      burden with convenient formulations, including fixed-dose combinations (FDCs).
      Darunavir, a HIV protease inhibitor, co-administered with low-dose ritonavir
      (800/100 mg once daily), is recommended in guidelines in combination with other
      antiretrovirals for HIV patients with no darunavir resistance-associated
      mutations. Cobicistat is an alternative agent to ritonavir for boosting plasma
      drug levels of darunavir among other antiretrovirals. Cobicistat is a more
      specific cytochrome P450 3A inhibitor than ritonavir without enzyme-inducing
      properties. This review describes the differing effects of cobicistat and
      ritonavir on metabolic enzymes, which explains their differing drug-drug
      interactions, and summarizes some of the studied drug-drug interactions for
      cobicistat. It also outlines the clinical development and data for a once-daily
      darunavir/cobicistat FDC. This FDC thus allows for a once-daily treatment regimen
      (including background antiretrovirals) with reduced pill burden. 

PMID- 25962101
TI  - Vaccine preventable meningitis in Malaysia: epidemiology and management.
AB  - Worldwide bacterial meningitis accounts for more than one million cases and
      135,000 deaths annually. Profound, lasting neurological complications occur in 9
      25% of cases. This review confirms the greatest risk from bacterial meningitis is
      in early life in Malaysia. Much of the disease burden can be avoided by
      immunization, particularly against Haemophilus influenzae type b (Hib) and
      Streptococcus pneumoniae. Despite inclusion of the Hib vaccine in the National
      Immunisation Programme and the licensure of pneumococcal vaccines, these two
      species are the main contributors to bacterial meningitis in Malaysia, with
      Neisseria meningitidis and Mycobacterium tuberculosis, causing a smaller
      proportion of disease. The high Hib prevalence may partly be due to dated, small
      scale studies limiting the understanding of the current epidemiological
      situation. This highlights the need for larger, better quality surveillance from
      Malaysia to evaluate the success of Hib immunization and to help guide
      immunization policy for vaccines against S. pneumoniae and N. meningitidis. 

PMID- 25962103
TI  - Eight-and-a-Half Syndrome.

PMID- 25962102
TI  - The Anthocyanin Delphinidin 3-Rutinoside Stimulates Glucagon-Like Peptide-1
      Secretion in Murine GLUTag Cell Line via the Ca2+/Calmodulin-Dependent Kinase II
      Pathway.
AB  - Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted from
      enteroendocrine L-cells. Although several nutrients induce GLP-1 secretion, there
      is little evidence to suggest that non-nutritive compounds directly increase GLP
      1 secretion. Here, we hypothesized that anthocyanins induce GLP-1 secretion and
      thereby significantly contribute to the prevention and treatment of diabetes.
      Delphinidin 3-rutinoside (D3R) was shown to increase GLP-1 secretion in GLUTag L
      cells. The results suggested that three hydroxyl or two methoxyl moieties on the
      aromatic ring are essential for the stimulation of GLP-1 secretion. Notably, the
      rutinose moiety was shown to be a potent enhancer of GLP-1 secretion, but only in
      conjunction with three hydroxyl moieties on the aromatic ring (D3R). Receptor
      antagonist studies revealed that D3R-stimulates GLP-1 secretion involving
      inositol 1,4,5-trisphosphate receptor-mediated intracellular Ca2+ mobilization.
      Treatment of GLUTag cells with a Ca2+/calmodulin-dependent kinaseII (CaMKII)
      inhibitor (KN-93) abolished D3R-stimulated GLP-1 secretion. In addition,
      treatment of GLUTag cells with D3R resulted in activation of CaMKII. Pre
      treatment of cells with a G protein-coupled receptor (GPR) 40/120 antagonist
      (GW1100) also significantly decreased D3R-stimulated GLP-1 secretion. These
      observations suggest that D3R stimulates GLP-1 secretion in GLUTag cells, and
      that stimulation of GLP-1 secretion by D3R is mediated via Ca2+-CaMKII pathway,
      which may possibly be mediated by GPR40/120. These findings provide a possible
      molecular mechanism of GLP-1 secretion in intestinal L-cells mediated by foods or
      drugs and demonstrate a novel biological function of anthocyanins in regards to
      GLP-1 secretion. 

PMID- 25962104
TI  - Using Community-Based Participatory Research to Disseminate a Mass Media Campaign
      Into Rural Communities.
AB  - The authors present the results of a media documentary, Weight of the Nation,
      disseminated in rural communities in the Brazos Valley region of east central
      Texas. Researchers relied on a community-based participatory research strategy to
      assure community participation in the implementation and evaluation of the media
      documentary in rural communities. To measure the short-term effects of the
      documentary, the research team used a mixed-methods approach of quantitative
      panel data from a pre/post survey, qualitative meeting notes, and observations
      from facilitated discussion groups. Results showed short-term increases in
      behavioral intention, as well as an increase in self and collective efficacy of
      participants to make healthy changes at individual and community levels to reduce
      obesity. The findings suggest that Weight of the Nation is a catalyst for
      increasing awareness about obesity and initiating changes in intention and
      efficacy perceptions. 

PMID- 25962107
TI  - Inhibition of Growth and Metastasis of Breast Cancer in Mice by Milk Fermented
      With Lactobacillus casei CRL 431.
AB  - Breast cancer is the second cause of death in women, who are especially related
      to uncontrolled metastasis. It was previously demonstrated that the
      administration of milk fermented by Lactobacillus casei CRL 431 [fermented milk
      (FM)] delayed the tumor growth in a murine breast cancer model. In this work we
      evaluated if the administration of FM to mice, starting when the tumor was
      measurable, can affect not only the tumor growth, but also the extravasation of
      tumor cells and the lung metastasis. The evaluation of immune cells-infiltrating
      tumors and lungs was also performed. Tumor volume was calculated. Whole blood,
      lungs, and liver were processed to count the number of colonies formed by tumor
      cells. Blood serum was obtained for monocyte chemoattractant protein-1,
      interleukin (IL)-10, and IL-6 determination, lung tissues for histologic
      observations, and tumor tissues for angiogenesis determination. Mice that
      received FM were compared with animals given milk or to the controls without any
      especial supplementation. The results showed that FM administration to mice
      decreased or suppressed tumor growth, with less tumor vascularity, extravasation
      of tumor cells, and lung metastasis. These benefits were associated to modulation
      of the immune response by decreasing the infiltration of macrophages in both the
      tumor and the lungs. FM administration maintained an increased antitumor response
      associated to CD8 lymphocytes, and also increased CD4 lymphocytes that can be
      involved in the modulation of the immune response. The future evaluation of
      cytokine profiles will allow knowing more about subpopulation of macrophages and
      lymphocytes associated to the beneficial effect of this probiotic in the breast
      cancer model. 

PMID- 25962106
TI  - Wogonin Inhibits Tumor-derived Regulatory Molecules by Suppressing STAT3
      Signaling to Promote Tumor Immunity.
AB  - Wogonin exerts effective antitumor activities through direct cytotoxicity against
      cancer cells and indirect immune modulation. However, the molecular mechanisms of
      these activities remain poorly understood and need further study. We found that
      wogonin could efficiently downregulate the expression of B7H1, retinoic acid
      early induced transcript-1epsilon (RAE-1epsilon), and vascular endothelial growth
      factor in gastric cancer cells. Wogonin also promoted the secretion of
      calreticulin and high-mobility group protein 1 by tumor cells. Apoptotic bodies
      from dying tumor cells treated with wogonin were susceptible for uptake by
      neighboring dendritic cells (DCs). With the xenograft tumor model, wogonin
      inhibited tumor growth and promoted the recruitment of DC, T, and NK cells into
      tumor tissues. Infiltrated frequencies of DC, T, and NK cells in tumors were
      inversely correlated with expression levels of vascular endothelial growth
      factor, B7H1, and RAE-1epsilon of tumor tissues. Wogonin directly inhibited the
      activation of STAT3 on tyrosine 705 in tumor cells. The dephosphorylation of
      STAT3 contributed to the decreased expression of B7H1 and MHC class I chain
      related protein A, and the enhancement of calreticulin on the cell membrane. Our
      study confirmed the immune-enhancing function of wogonin, and indicated that
      wogonin could be used in collaboration with DC vaccine or activated lymphocytes
      for tumor therapy. 

PMID- 25962109
TI  - Administration of ipilimumab to a liver transplant recipient with unresectable
      metastatic melanoma.
AB  - The CTLA-4 immune checkpoint inhibitor ipilimumab improves overall survival in
      metastatic melanoma. Its use in organ transplant recipients has not been studied
      and has been reported once in the literature. We report the case of a 59-year-old
      liver transplant patient who was given ipilimumab after previous treatment for
      advanced melanoma. She did not experience organ rejection, immune-related adverse
      events, or evidence of tumor regression. 

PMID- 25962108
TI  - Engineering NK Cells Modified With an EGFRvIII-specific Chimeric Antigen Receptor
      to Overexpress CXCR4 Improves Immunotherapy of CXCL12/SDF-1alpha-secreting
      Glioblastoma.
AB  - Natural killer (NK) cells are promising effector cells for adjuvant immunotherapy
      of cancer. So far, several preclinical studies have shown the feasibility of gene
      engineered NK cells, which upon expression of chimeric antigen receptors (CARs)
      are redirected to otherwise NK cell-resistant tumors. Yet, we reasoned that the
      efficiency of an immunotherapy using CAR-modified NK cells critically relies on
      efficient migration to the tumor site and might be improved by the engraftment of
      a receptor specific for a chemokine released by the tumor. On the basis of the
      DNAX-activation protein 12 (DAP12), a signaling adapter molecule involved in
      signal transduction of activating NK cell receptors, we constructed an epidermal
      growth factor variant III (EGFRvIII)-CAR, designated MR1.1-DAP12 which confers
      specific cytotoxicity of NK cell towards EGFRvIII glioblastoma cells in vitro and
      to established subcutaneous U87-MG tumor xenografts. So far, infusion of NK cells
      with expression of MR1.1-DAP12 caused a moderate but significantly delayed tumor
      growth and increased median survival time when compared with NK cells transduced
      with an ITAM-defective CAR. Notably, the further genetic engineering of these
      EGFRvIII-specific NK cells with the chemokine receptor CXCR4 conferred a specific
      chemotaxis to CXCL12/SDF-1alpha secreting U87-MG glioblastoma cells. Moreover,
      the administration of such NK cells resulted in complete tumor remission in a
      number of mice and a significantly increased survival when compared with the
      treatment of xenografts with NK cells expressing only the EGFRvIII-specific CAR
      or mock control. We conclude that chemokine receptor-engineered NK cells with
      concomitant expression of a tumor-specific CAR are a promising tool to improve
      adoptive tumor immunotherapy. 

PMID- 25962110
TI  - Autoimmune Colitis and Subsequent CMV-induced Hepatitis After Treatment With
      Ipilimumab.
AB  - Ipilimumab, a humanized CTLA-4 antibody, improves overall survival in patients
      with metastatic melanoma. However, immune-related adverse effects occur in about
      65% of ipilimumab-treated patients and have to be adequately managed. A 55-year
      old patient developed grade 3 autoimmune colitis 7 weeks after initiation of
      ipilimumab treatment and subsequently hepatitis with grade 3 elevation of
      transaminases and gamma-glutamyl transferase. Colitis manifested with up to 18
      watery and bloody stools per day and severe attacks of abdominal pain. After
      exclusion of infectious causes, immunosuppression with corticosteroids was
      initiated. Because of recurrent abdominal pain, spontaneous perforation of the
      colon had to be excluded. Elevated liver function tests (grade 3 CTCAE) occurred
      and differential diagnosis included immune-mediated, toxic, and viral hepatitis.
      It is interesting to note that, not an immune-mediated but a cytomegalovirus
      induced hepatitis was diagnosed by serum blood tests and liver biopsy and was
      subsequently successfully treated. Careful elaboration of the patient under
      immunotherapy was essential as further immunosuppression mandatory for autoimmune
      hepatitis would have worsened the viral hepatitis. In conclusion, cytomegalovirus
      reactivation should be included in the differential in patients under
      immunotherapy with checkpoint inhibitors and has to be considered as a cause for
      morbidity. 

PMID- 25962111
TI  - Recellularization of decellularized lung scaffolds is enhanced by dynamic
      suspension culture.
AB  - Strategies are needed to improve repopulation of decellularized lung scaffolds
      with stromal and functional epithelial cells. We demonstrate that decellularized
      mouse lungs recellularized in a dynamic low fluid shear suspension bioreactor,
      termed the rotating wall vessel (RWV), contained more cells with decreased
      apoptosis, increased proliferation and enhanced levels of total RNA compared to
      static recellularization conditions. These results were observed with two
      relevant mouse cell types: bone marrow-derived mesenchymal stromal (stem) cells
      (MSCs) and alveolar type II cells (C10). In addition, MSCs cultured in
      decellularized lungs under static but not bioreactor conditions formed
      multilayered aggregates. Gene expression and immunohistochemical analyses
      suggested differentiation of MSCs into collagen I-producing fibroblast-like cells
      in the bioreactor, indicating enhanced potential for remodeling of the
      decellularized scaffold matrix. In conclusion, dynamic suspension culture is
      promising for enhancing repopulation of decellularized lungs, and could
      contribute to remodeling the extracellular matrix of the scaffolds with
      subsequent effects on differentiation and functionality of inoculated cells. 

PMID- 25962112
TI  - Genotypic distribution of hepatitis C virus in Thailand and Southeast Asia.
AB  - The majority of hepatitis C virus (HCV) infection results in chronic infection,
      which can lead to liver cirrhosis and hepatocellular carcinoma. Global burden of
      hepatitis C virus (HCV) is estimated at 150 million individuals, or 3% of the
      world's population. The distribution of the seven major genotypes of HCV varies
      with geographical regions. Since Asia has a high incidence of HCV, we assessed
      the distribution of HCV genotypes in Thailand and Southeast Asia. From 588 HCV
      positive samples obtained throughout Thailand, we characterized the HCV 5'
      untranslated region, Core, and NS5B regions by nested PCR. Nucleotide sequences
      obtained from both the Core and NS5B of these isolates were subjected to
      phylogenetic analysis, and genotypes were assigned using published reference
      genotypes. Results were compared to the epidemiological data of HCV genotypes
      identified within Southeast Asian. Among the HCV subtypes characterized in the
      Thai samples, subtype 3a was the most predominant (36.4%), followed by 1a
      (19.9%), 1b (12.6%), 3b (9.7%) and 2a (0.5%). While genotype 1 was prevalent
      throughout Thailand (27-36%), genotype 3 was more common in the south. Genotype 6
      (20.9%) constituted subtype 6f (7.8%), 6n (7.7%), 6i (3.4%), 6j and 6m (0.7%
      each), 6c (0.3%), 6v and 6xa (0.2% each) and its prevalence was significantly
      lower in southern Thailand compared to the north and northeast (p = 0.027 and p =
      0.030, respectively). Within Southeast Asia, high prevalence of genotype 6
      occurred in northern countries such as Myanmar, Laos, and Vietnam, while genotype
      3 was prevalent in Thailand and Malaysia. Island nations of Singapore, Indonesia
      and Philippines demonstrated prevalence of genotype 1. This study further
      provides regional HCV genotype information that may be useful in fostering sound
      public health policy and tracking future patterns of HCV spread. 

PMID- 25962113
TI  - Structure based in silico analysis of quinolone resistance in clinical isolates
      of Salmonella Typhi from India.
AB  - Enteric fever is a major cause of morbidity in several parts of the Indian
      subcontinent. The treatment for typhoid fever majorly includes the
      fluoroquinolone group of antibiotics. Excessive and indiscriminate use of these
      antibiotics has led to development of acquired resistance in the causative
      organism Salmonella Typhi. The resistance towards fluoroquinolones is associated
      with mutations in the target gene of DNA Gyrase. We have estimated the Minimum
      Inhibitory Concentration (MIC) of commonly used fluoroquinolone representatives
      from three generations, ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin,
      for 100 clinical isolates of Salmonella Typhi from patients in the Indian
      subcontinent. The MICs have been found to be in the range of 0.032 to 8 MUg/ml.
      The gene encoding DNA Gyrase was subsequently sequenced and point mutations were
      observed in DNA Gyrase in the quinolone resistance determining region comprising
      Ser83Phe/Tyr and Asp87Tyr/Gly. The binding ability of these four fluoroquinolones
      in the quinolone binding pocket of wild type as well as mutant DNA Gyrase was
      computationally analyzed by molecular docking to assess their differential
      binding behaviour. This study has revealed that mutations in DNA Gyrase alter the
      characteristics of the binding pocket resulting in the loss of crucial molecular
      interactions and consequently decrease the binding affinity of fluoroquinolones
      with the target protein. The present study assists in understanding the
      underlying molecular and structural mechanism for decreased fluoroquinolone
      susceptibility in clinical isolates as a consequence of mutations in DNA Gyrase. 

PMID- 25962114
TI  - Epirubicin, Cisplatin, and Capecitabine for Primary Platinum-Resistant or
      Platinum-Refractory Epithelial Ovarian Cancer: Results of a Retrospective, Single
      Institution Study.
AB  - OBJECTIVE: Primary platinum-resistant epithelial ovarian cancer (EOC) is an area
      of unmet medical need. There is limited evidence from small studies that platinum
      based combinations can overcome "resistance" in a proportion of patients. We
      investigated the efficacy and toxicity of platinum-based combination chemotherapy
      in the platinum-resistant and platinum-refractory setting. METHODS: Epirubicin,
      cisplatin, and capecitabine (ECX) combination chemotherapy was used at our
      institution for the treatment of relapsed EOC. From the institutional database,
      we identified all patients with primary platinum-refractory or platinum-resistant
      relapse treated with ECX as second-line therapy between 2001 and 2012. We
      extracted demographic, clinical, treatment, and toxicity data and outcomes. We
      used logistic and Cox regression models to identify predictors of response and
      survival respectively. RESULTS: Thirty-four 34 patients (8 refractory, 26
      resistant) were treated with ECX. Response Evaluation Criteria In Solid Tumors
      (RECIST) response rate was 45%, median progression-free survival (PFS) was 6.4
      months, and overall survival (OS) was 10.6 months. Platinum-resistant patients
      had better outcomes than did platinum-refractory patients (response rate, 54% vs
      0%, P = 0.047; PFS 7.2 vs 1.8 months, P < 0.0001; OS 14.4 vs 3 months, P <
      0.001). In regression models, time to progression after first-line treatment and
      platinum-refractory status were the strongest predictors of response and PFS or
      OS, respectively. Patients with time to progression after first-line treatment
      longer than 3 months showed PFS and OS of 7.9 and 14.7 months, respectively.
      Toxicity was manageable, with only 13% of cycles administered at reduced doses.
      CONCLUSIONS: Epirubicin, cisplatin, and capecitabine seems to be active in
      platinum-resistant relapsed EOC with manageable toxicity. Further prospective
      investigation of platinum-anthracycline combinations is warranted in patients who
      relapse 3 to 6 months after first-line platinum-taxane treatment.

PMID- 25962115
TI  - Up-Regulation of miR-204 Enhances Anoikis Sensitivity in Epithelial Ovarian
      Cancer Cell Line Via Brain-Derived Neurotrophic Factor Pathway In Vitro.
AB  - OBJECTIVE: Genomic loci encoding miR-204, which was predicted to target brain
      derived neurotrophic factor (BDNF), were frequently lost in multiple cancer,
      including epithelial ovarian cancer (EOC). In this study, we aimed to find out
      the influence of miR-204 expression level on EOC cell anoikis sensitivity and to
      explore possible mechanisms of this process. METHODS: First, we screened EOC
      cells, which maintain anoikis resistance forming an anoikis pattern. miR-204
      expression level and apoptosis were measured, respectively, by quantitative
      reverse transcriptase polymerase chain reaction and Annexin-V-R-PE/7-amino
      actinomycin assay. Then we restored the expression level of miR-204 by
      transfection with pre-miR-204. miR-204 expression level and apoptosis were
      measured as before; cell invasion and migration ability were detected by
      transwell invasion assay and wound-healing assay. The messenger RNA level of BDNF
      was also detected by quantitative reverse transcriptase polymerase chain
      reaction; Western blot analysis was performed to assess pAKT expression. RESULTS:
      Expression of miR-204 is significantly down-regulated in an anoikis pattern.
      Restored expression level of miR-204 enables cells to acquire more sensitivity to
      anoikis and decrease invasive and metastatic behavior, and also results in BDNF
      down-expression and inhibits activation of mitochondria-dependent pathway through
      the PI3K/AKT signaling pathway leading to cancer cell anoikis in EOC cells.
      CONCLUSIONS: miR-204 up-regulation may be linked directly to the sensitivity of
      EOC cell anoikis by contributing to BDNF down-regulation. Our findings provide a
      novel mechanism for manipulating miR-204 levels therapeutically to restore
      anoikis sensitivity.

PMID- 25962116
TI  - Postoperative Complications After Distal Pancreatectomy Performed During
      Cytoreductive Surgery for Gynecologic Malignancies.
AB  - OBJECTIVES: To investigate the incidence of pancreatic leak and other
      postoperative complications after distal pancreatectomy performed during
      debulking surgery for gynecologic malignancies. METHODS: All patients who
      underwent distal pancreatectomy during their debulking surgery from 2010 to 2014
      were identified. Postoperative complications within 30 days and pancreatic leak
      within 120 days after surgery were included. RESULTS: Eighteen patients met the
      inclusion criteria. The median age was 62 years (36-78 years). Four patients
      (22%) were admitted to the intensive care unit, and the average length of
      hospital stay was 10 days. Nine patients developed postoperative complications
      within 30 days after surgery (50%) with no perioperative mortality up to 90 days
      after surgery. No patients required reexploration. The median time from surgery
      to initiation of chemotherapy was 39.5 days. Two patients developed pancreatic
      leak (11%). Among the patients who developed pancreatic leak, the average length
      of hospital stay was 11.5 days and time to initiation of chemotherapy was 75
      days. Conservative management was successful in both cases. CONCLUSION: In this
      series, the rate of pancreatic leak was lower than previously reported with no
      perioperative mortality or surgical reexploration. However, the time to
      initiation of chemotherapy was delayed in those who developed pancreatic leak.
      These data are important in patient counseling and decision making at the time of
      debulking surgery. Gynecologic oncologists considering distal pancreatectomy
      should be familiar with perioperative management of these patients.

PMID- 25962117
TI  - A small, microRNA-size, ribonucleic acid regulating gene expression and
      development of Shiga toxin-converting bacteriophage Phi24Beta.
AB  - A microRNA-size (20-nt long) molecule has been identified in Escherichia coli
      after induction of Shiga toxin-converting bacteriophage Phi24B. This small RNA,
      named 24B_1, is encoded in the lom-vb_24B_43 region of the phage genome, and
      apparently it is produced by cleavage of a larger transcript. A phage devoid of
      24B_1 revealed decreased efficiency of lysogenization, quicker prophage induction
      after provoking the SOS response, higher efficiency of progeny phage production
      during the lytic cycle and less efficient adsorption on the host cells.
      Expression of most of phage genes was drastically increased after infection of E.
      coli by the Phi24BDelta24B_1 phage. Since 24B_1 may impair expression of the
      d_ant gene, coding for an anti-repressor, these results may explain the mechanism
      of regulations of the physiological processes by this small RNA due to impaired
      activity of the cI repressor and changed expression of vast majority of phage
      genes. To our knowledge, this is the first example of functional microRNA-size
      molecule in bacterial cells. 

PMID- 25962119
TI  - A global biomedical R&D fund and mechanism for innovations of public health
      importance.

PMID- 25962118
TI  - HPTN 062: A Pilot Randomized Controlled Trial Exploring the Effect of a
      Motivational-Interviewing Intervention on Sexual Behavior among Individuals with
      Acute HIV Infection in Lilongwe, Malawi.
AB  - OBJECTIVE: We pilot tested a Motivational Interviewing (MI) -based counseling
      intervention for individuals with Acute HIV Infection (AHI) to reduce risky
      sexual behavior in Lilongwe, Malawi. METHODS: Twenty-eight individuals diagnosed
      with AHI were randomized to receive either brief education alone, or the brief
      education plus the MI-based intervention, called Uphungu Wanga. Participants in
      Uphungu Wanga received four sessions delivered on the day of diagnosis, three
      days later and at weeks 1 and 2 with a booster session at week 8; participants
      were followed for 24 weeks from diagnosis. An interviewer administered
      quantitative questionnaire was conducted at baseline and at weeks 2, 4, 8, 12,
      16, 20 and 24. Semi-structured qualitative interviews (SSI) were conducted at
      weeks 2, 8, 12, and 24. RESULTS: The majority of participants in both arms
      reported rapid and sustained behavior change following diagnosis with AHI. Very
      few participants reported having sex without a condom after diagnosis.
      Participants reported a trend towards fewer sex partners and abstaining from sex
      during study follow-up. Participants in the MI-based arm provided concrete
      examples of risk reduction strategies in the SSIs while those in the brief
      education arm primarily described reducing risk behavior, suggesting that the MI
      based group may have acquired more risk reduction skills. CONCLUSIONS:
      Individuals in both study arms reduced risky sexual behaviors after diagnosis
      with AHI. We found few major differences between study arms during the 6-month
      follow up period in self-reported sexual behaviors therefore a MI-based
      intervention may not be needed to trigger behavior change following AHI. However,
      comparing the MI-based intervention to repeated brief education sessions made it
      difficult to assess the potential benefit of an MI-based intervention in a
      setting where standard counseling often consists of one post-test session.
      Nevertheless, provision of counseling immediately following diagnosis with HIV to
      support behavior change should remain a priority. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01197027.

PMID- 25962120
TI  - Negative feedback-defective PRPS1 mutants drive thiopurine resistance in relapsed
      childhood ALL.
AB  - Relapse is the leading cause of mortality in children with acute lymphoblastic
      leukemia (ALL). Among chemotherapeutics, thiopurines are key drugs in ALL
      combination therapy. Using whole-exome sequencing, we identified relapse-specific
      mutations in the phosphoribosyl pyrophosphate synthetase 1 gene (PRPS1), which
      encodes a rate-limiting purine biosynthesis enzyme, in 24/358 (6.7%) relapsed
      childhood B cell ALL (B-ALL) cases. All individuals who harbored PRPS1 mutations
      relapsed early during treatment, and mutated ALL clones expanded exponentially
      before clinical relapse. Our functional analyses of PRPS1 mutants uncovered a new
      chemotherapy-resistance mechanism involving reduced feedback inhibition of de
      novo purine biosynthesis and competitive inhibition of thiopurine activation.
      Notably, the de novo purine synthesis inhibitor lometrexol effectively abrogated
      PRPS1 mutant-driven drug resistance. These results highlight the importance of
      constitutive activation of the de novo purine synthesis pathway in thiopurine
      resistance, and they offer therapeutic strategies for the treatment of relapsed
      and thiopurine-resistant ALL. 

PMID- 25962121
TI  - Pharmacological targeting of actin-dependent dynamin oligomerization ameliorates
      chronic kidney disease in diverse animal models.
AB  - Dysregulation of the actin cytoskeleton in podocytes represents a common pathway
      in the pathogenesis of proteinuria across a spectrum of chronic kidney diseases
      (CKD). The GTPase dynamin has been implicated in the maintenance of cellular
      architecture in podocytes through its direct interaction with actin. Furthermore,
      the propensity of dynamin to oligomerize into higher-order structures in an actin
      dependent manner and to cross-link actin microfilaments into higher-order
      structures has been correlated with increased actin polymerization and global
      organization of the actin cytoskeleton in the cell. We found that use of the
      small molecule Bis-T-23, which promotes actin-dependent dynamin oligomerization
      and thus increased actin polymerization in injured podocytes, was sufficient to
      improve renal health in diverse models of both transient kidney disease and CKD.
      In particular, administration of Bis-T-23 in these renal disease models restored
      the normal ultrastructure of podocyte foot processes, lowered proteinuria,
      lowered collagen IV deposits in the mesangial matrix, diminished mesangial matrix
      expansion and extended lifespan. These results further establish that alterations
      in the actin cytoskeleton of kidney podocytes is a common hallmark of CKD, while
      also underscoring the substantial regenerative potential of injured glomeruli and
      identifying the oligomerization cycle of dynamin as an attractive potential
      therapeutic target to treat CKD. 

PMID- 25962122
TI  - Common clonal origin of central and resident memory T cells following skin
      immunization.
AB  - Central memory T (TCM) cells in lymph nodes (LNs) and resident memory T (TRM)
      cells in peripheral tissues have distinct roles in protective immunity. Both are
      generated after primary infections, but their clonal origins have been unclear.
      To address this question, we immunized mice through the skin with a protein
      antigen, a chemical hapten, or a non-replicating poxvirus. We then analyzed
      antigen-activated T cells from different tissues using high-throughput sequencing
      (HTS) of the gene encoding the T cell receptor (TCR) beta-chain (Trb, also known
      as Tcrb) using CDR3 sequences to simultaneously track thousands of unique T
      cells. For every abundant TRM cell clone generated in the skin, an abundant TCM
      cell clone bearing the identical TCR was present in the LNs. Thus, antigen
      reactive skin TRM and LN TCM cell clones were derived from a common naive T cell
      precursor after skin immunization, generating overlapping TCR repertoires.
      Although they bore the same TCR, TRM cells mediated rapid contact
      hypersensitivity responses, whereas TCM cells mediated delayed and attenuated
      responses. Studies in human subjects confirmed the generation of skin TRM cells
      in allergic contact dermatitis. Thus, immunization through skin simultaneously
      generates skin TRM and LN TCM cells in similar numbers from the same naive T
      cells. 

PMID- 25962123
TI  - Metabolic regulation of hepatitis B immunopathology by myeloid-derived suppressor
      cells.
AB  - Infection with hepatitis B virus (HBV) results in disparate degrees of tissue
      injury: the virus can either replicate without pathological consequences or
      trigger immune-mediated necroinflammatory liver damage. We investigated the
      potential for myeloid-derived suppressor cells (MDSCs) to suppress T cell
      mediated immunopathology in this setting. Granulocytic MDSCs (gMDSCs) expanded
      transiently in acute resolving HBV, decreasing in frequency prior to peak hepatic
      injury. In persistent infection, arginase-expressing gMDSCs (and circulating
      arginase) increased most in disease phases characterized by HBV replication
      without immunopathology, whilst L-arginine decreased. gMDSCs expressed liver
      homing chemokine receptors and accumulated in the liver, their expansion
      supported by hepatic stellate cells. We provide in vitro and ex vivo evidence
      that gMDSCs potently inhibited T cells in a partially arginase-dependent manner.
      L-arginine-deprived T cells upregulated system L amino acid transporters to
      increase uptake of essential nutrients and attempt metabolic reprogramming. These
      data demonstrate the capacity of expanded arginase-expressing gMDSCs to regulate
      liver immunopathology in HBV infection. 

PMID- 25962124
TI  - Astaxanthin from Haematococcus pluvialis Prevents Oxidative Stress on Human
      Endothelial Cells without Toxicity.
AB  - Astaxanthin, a powerful antioxidant, is a good candidate for the prevention of
      intracellular oxidative stress. The aim of the study was to compare the
      antioxidant activity of astaxanthin present in two natural extracts from
      Haematococcus pluvialis, a microalgae strain, with that of synthetic astaxanthin.
      Natural extracts were obtained either by solvent or supercritical extraction
      methods. UV, HPLC-DAD and (HPLC-(atmospheric pressure chemical ionization
      (APCI)+)/ion trap-MS) characterizations of both natural extracts showed similar
      compositions of carotenoids, but different percentages in free astaxanthin and
      its ester derivatives. The Trolox equivalent antioxidant capacity (TEAC) assay
      showed that natural extracts containing esters displayed stronger antioxidant
      activities than free astaxanthin. Their antioxidant capacities to inhibit
      intracellular oxidative stress were then evaluated on HUVEC cells. The
      intracellular antioxidant activity in natural extracts was approximately 90-times
      higher than synthetic astaxanthin (5 uM). No modification, neither in the
      morphology nor in the viability, of vascular human cells was observed by in vitro
      biocompatibility study up to 10 uM astaxanthin concentrations. Therefore, these
      results revealed the therapeutic potential of the natural extracts in vascular
      human cell protection against oxidative stress without toxicity, which could be
      exploited in prevention and/or treatment of cardiovascular diseases. 

PMID- 25962126
TI  - Electronic Cigarettes: Aggregate Harm.

PMID- 25962125
TI  - A novel caspase 8 selective small molecule potentiates TRAIL-induced cell death.
AB  - Recombinant soluble TRAIL and agonistic antibodies against TRAIL receptors (DR4
      and DR5) are currently being created for clinical cancer therapy, due to their
      selective killing of cancer cells and high safety characteristics. However,
      resistance to TRAIL and other targeted therapies is an important issue facing
      current cancer research field. An attractive strategy to sensitize resistant
      malignancies to TRAIL-induced cell death is the design of small molecules that
      target and promote caspase 8 activation. For the first time, we describe the
      discovery and characterization of a small molecule that directly binds caspase 8
      and enhances its activation when combined with TRAIL, but not alone. The molecule
      was identified through an in silico chemical screen for compounds with affinity
      for the caspase 8 homodimer's interface. The compound was experimentally
      validated to directly bind caspase 8, and to promote caspase 8 activation and
      cell death in single living cells or population of cells, upon TRAIL stimulation.
      Our approach is a proof-of-concept strategy leading to the discovery of a novel
      small molecule that not only stimulates TRAIL-induced apoptosis in cancer cells,
      but may also provide insights into the structure-function relationship of caspase
      8 homodimers as putative targets in cancer. 

PMID- 25962127
TI  - On Chlorofluorocarbon Bans and Inhaled Albuterol Prices.

PMID- 25962129
TI  - Hemorrhagic Stroke Probably Caused by Exercise Combined With a Sports Supplement
      Containing beta-Methylphenylethylamine (BMPEA): A Case Report.

PMID- 25962128
TI  - The Impact of the US Food and Drug Administration Chlorofluorocarbon Ban on Out
      of-pocket Costs and Use of Albuterol Inhalers Among Individuals With Asthma.
AB  - IMPORTANCE: The US Clean Air Act prohibits use of nonessential ozone-depleting
      substances. In 2005, the US Food and Drug Administration announced the ban of
      chlorofluorocarbon (CFC) albuterol inhalers by December 31, 2008. The policy
      resulted in the controversial replacement of generic CFC inhalers by more
      expensive, branded hydrofluoroalkane inhalers. The policy's impact on out-of
      pocket costs and utilization of albuterol is unknown. OBJECTIVE: To study the
      impact of the US Food and Drug Administration's CFC ban on out-of-pocket costs
      and utilization of albuterol inhalers. DESIGN, SETTING, AND PARTICIPANTS: Using
      private insurance data from January 1, 2004, to December 31, 2010, we
      investigated the effect of the CFC ban on out-of-pocket costs and utilization of
      albuterol inhalers among individuals with asthma (109,428 adults; 37,281
      children), as well as asthma-related hospitalizations, emergency department
      visits, and outpatient visits. We estimated multivariable models adjusted for
      age, sex, comorbidities, and mean out-of-pocket costs of albuterol inhalers in an
      individual's drug plan. We analyzed whether effects varied between adults vs
      children and those with persistent vs nonpersistent asthma. MAIN OUTCOMES AND
      MEASURES: Pharmacy claims for albuterol inhalers, as well as asthma-related
      hospitalizations, emergency department visits, and outpatient visits. RESULTS:
      The mean out-of-pocket albuterol cost rose from $13.60 (95% CI, $13.40-$13.70)
      per prescription in 2004 to $25.00 (95% CI, $24.80-$25.20) immediately after the
      2008 ban. By the end of 2010, costs had lowered to $21.00 (95% CI, $20.80-$21.20)
      per prescription. Overall albuterol inhaler use steadily declined from 2004 to
      2010. Steep declines in use of generic CFC inhalers occurred after the fourth
      quarter of 2006 and were almost fully offset by increases in use of
      hydrofluoroalkane inhalers. In multivariable analyses, a $10 increase in out-of
      pocket albuterol prescription costs was estimated to lower utilization by 0.92
      percentage points (95% CI, -1.39 to -0.44; P < .001) for adults and 0.54
      percentage points (95% CI, -0.84 to -0.24; P = .001) for children, with no
      difference between adults vs children and patients with persistent vs
      nonpersistent asthma and with no impact on asthma-related hospitalizations,
      emergency department visits, and outpatient visits. CONCLUSIONS AND RELEVANCE:
      The Federal ban of CFC inhalers led to large relative increases in out-of-pocket
      albuterol costs among privately insured individuals with asthma and modest
      declines in utilization. The policy's impact on individuals without insurance,
      who faced greater cost increases, is unknown.

PMID- 25962130
TI  - The Avalanche Hypothesis and Compression of Morbidity: Testing Assumptions
      through Cohort-Sequential Analysis.
AB  - BACKGROUND: The compression of morbidity model posits a breakpoint in the adult
      lifespan that separates an initial period of relative health from a subsequent
      period of ever increasing morbidity. Researchers often assume that such a
      breakpoint exists; however, this assumption is hitherto untested. PURPOSE: To
      test the assumption that a breakpoint exists--which we term a morbidity tipping
      point--separating a period of relative health from a subsequent deterioration in
      health status. An analogous tipping point for healthcare costs was also
      investigated. METHODS: Four years of adults' (N = 55,550) morbidity and costs
      data were retrospectively analyzed. Data were collected in Pittsburgh, PA between
      2006 and 2009; analyses were performed in Rochester, NY and Ann Arbor, MI in 2012
      and 2013. Cohort-sequential and hockey stick regression models were used to
      characterize long-term trajectories and tipping points, respectively, for both
      morbidity and costs. RESULTS: Morbidity increased exponentially with age
      (P<.001). A morbidity tipping point was observed at age 45.5 (95% CI, 41.3-49.7).
      An exponential trajectory was also observed for costs (P<.001), with a costs
      tipping point occurring at age 39.5 (95% CI, 32.4-46.6). Following their
      respective tipping points, both morbidity and costs increased substantially
      (Ps<.001). CONCLUSIONS: Findings support the existence of a morbidity tipping
      point, confirming an important but untested assumption. This tipping point,
      however, may occur earlier in the lifespan than is widely assumed. An "avalanche
      of morbidity" occurred after the morbidity tipping point-an ever increasing rate
      of morbidity progression. For costs, an analogous tipping point and "avalanche"
      were observed. The time point at which costs began to increase substantially
      occurred approximately 6 years before health status began to deteriorate.

PMID- 25962131
TI  - Proflavine Hemisulfate as a Fluorescent Contrast Agent for Point-of-Care
      Cytology.
AB  - Proflavine hemisulfate, an acridine-derived fluorescent dye, can be used as a
      rapid stain for cytologic examination of biological specimens. Proflavine
      fluorescently stains cell nuclei and cytoplasmic structures, owing to its small
      amphipathic structure and ability to intercalate DNA. In this manuscript, we
      demonstrated the use of proflavine as a rapid cytologic dye on a number of
      specimens, including normal exfoliated oral squamous cells, cultured human oral
      squamous carcinoma cells, and leukocytes derived from whole blood specimens using
      a custom-built, portable, LED-illuminated fluorescence microscope. No incubation
      time was needed after suspending cells in 0.01% (w/v) proflavine diluted in
      saline. Images of proflavine stained oral cells had clearly visible nuclei as
      well as granular cytoplasm, while stained leukocytes exhibited bright nuclei, and
      highlighted the multilobar nature of nuclei in neutrophils. We also demonstrated
      the utility of quantitative analysis of digital images of proflavine stained
      cells, which can be used to detect significant morphological differences between
      different cell types. Proflavine stained oral cells have well-defined nuclei and
      cell membranes which allowed for quantitative analysis of nuclear to cytoplasmic
      ratios, as well as image texture analysis to extract quantitative image features.

PMID- 25962132
TI  - Forskolin suppresses delayed-rectifier K+ currents and enhances spike frequency
      dependent adaptation of sympathetic neurons.
AB  - In signal transduction research natural or synthetic molecules are commonly used
      to target a great variety of signaling proteins. For instance, forskolin, a
      diterpene activator of adenylate cyclase, has been widely used in cellular
      preparations to increase the intracellular cAMP level. However, it has been shown
      that forskolin directly inhibits some cloned K+ channels, which in excitable
      cells set up the resting membrane potential, the shape of action potential and
      regulate repetitive firing. Despite the growing evidence indicating that K+
      channels are blocked by forskolin, there are no studies yet assessing the impact
      of this mechanism of action on neuron excitability and firing patterns. In
      sympathetic neurons, we find that forskolin and its derivative 1,9
      Dideoxyforskolin, reversibly suppress the delayed rectifier K+ current (IKV).
      Besides, forskolin reduced the spike afterhyperpolarization and enhanced the
      spike frequency-dependent adaptation. Given that IKV is mostly generated by Kv2.1
      channels, HEK-293 cells were transfected with cDNA encoding for the Kv2.1 alpha
      subunit, to characterize the mechanism of forskolin action. Both drugs reversible
      suppressed the Kv2.1-mediated K+ currents. Forskolin inhibited Kv2.1 currents and
      IKV with an IC50 of ~32 MUM and ~24 uM, respectively. Besides, the drug induced
      an apparent current inactivation and slowed-down current deactivation. We suggest
      that forskolin reduces the excitability of sympathetic neurons by enhancing the
      spike frequency-dependent adaptation, partially through a direct block of their
      native Kv2.1 channels. 

PMID- 25962133
TI  - Correction: Predictors of Immunological Failure of Antiretroviral Therapy among
      HIV Infected Patients in Ethiopia: A Matched Case-Control Study.

PMID- 25962135
TI  - Resource construction and evaluation for indirect opinion mining of drug reviews.
AB  - Opinion mining is a well-known problem in natural language processing that has
      attracted increasing attention in recent years. Existing approaches are mainly
      limited to the identification of direct opinions and are mostly dedicated to
      explicit opinions. However, in some domains such as medical, the opinions about
      an entity are not usually expressed by opinion words directly, but they are
      expressed indirectly by describing the effect of that entity on other ones.
      Therefore, ignoring indirect opinions can lead to the loss of valuable
      information and noticeable decline in overall accuracy of opinion mining systems.
      In this paper, we first introduce the task of indirect opinion mining. Then, we
      present a novel approach to construct a knowledge base of indirect opinions,
      called OpinionKB, which aims to be a resource for automatically classifying
      people's opinions about drugs. Using our approach, we have extracted 896
      quadruples of indirect opinions at a precision of 88.08 percent. Furthermore,
      experiments on drug reviews demonstrate that our approach can achieve 85.25
      percent precision in polarity detection task, and outperforms the state-of-the
      art opinion mining methods. We also build a corpus of indirect opinions about
      drugs, which can be used as a basis for supervised indirect opinion mining. The
      proposed approach for corpus construction achieves the precision of 88.42
      percent. 

PMID- 25962134
TI  - PSMC5, a 19S Proteasomal ATPase, Regulates Cocaine Action in the Nucleus
      Accumbens.
AB  - DeltaFosB is a stable transcription factor which accumulates in the nucleus
      accumbens (NAc), a key part of the brain's reward circuitry, in response to
      chronic exposure to cocaine or other drugs of abuse. While DeltaFosB is known to
      heterodimerize with a Jun family member to form an active transcription factor
      complex, there has not to date been an open-ended exploration of other possible
      binding partners for DeltaFosB in the brain. Here, by use of yeast two-hybrid
      assays, we identify PSMC5-also known as SUG1, an ATPase-containing subunit of the
      19S proteasomal complex-as a novel interacting protein with DeltaFosB. We verify
      such interactions between endogenous DeltaFosB and PSMC5 in the NAc and
      demonstrate that both proteins also form complexes with other chromatin
      regulatory proteins associated with gene activation. We go on to show that
      chronic cocaine increases nuclear, but not cytoplasmic, levels of PSMC5 in the
      NAc and that overexpression of PSMC5 in this brain region promotes the locomotor
      responses to cocaine. Together, these findings describe a novel mechanism that
      contributes to the actions of DeltaFosB and, for the first time, implicates PSMC5
      in cocaine-induced molecular and behavioral plasticity. 

PMID- 25962136
TI  - Formulation, high throughput in vitro screening and in vivo functional
      characterization of nanoemulsion-based intranasal vaccine adjuvants.
AB  - Vaccine adjuvants have been reported to induce both mucosal and systemic immunity
      when applied to mucosal surfaces and this dual response appears important for
      protection against certain pathogens. Despite the potential advantages, however,
      no mucosal adjuvants are currently approved for human use. Evaluating compounds
      as mucosal adjuvants is a slow and costly process due to the need for lengthy
      animal immunogenicity studies. We have constructed a library of 112 intranasal
      adjuvant candidate formulations consisting of oil-in-water nanoemulsions that
      contain various cationic and nonionic surfactants. To facilitate adjuvant
      development we first evaluated this library in a series of high-throughput, in
      vitro assays for activities associated with innate and adaptive immune activation
      in vivo. These in vitro assays screened for the ability of the adjuvant to bind
      to mucin, induce cytotoxicity, facilitate antigen uptake in epithelial and
      dendritic cells, and activate cellular pathways. We then sought to determine how
      these parameters related to adjuvant activity in vivo. While the in vitro assays
      alone were not enough to predict the in vivo adjuvant activity completely,
      several interesting relationships were found with immune responses in mice.
      Furthermore, by varying the physicochemical properties of the surfactant
      components (charge, surfactant polar head size and hydrophobicity) and the
      surfactant blend ratio of the formulations, the strength and type of the immune
      response generated (TH1, TH2, TH17) could be modulated. These findings suggest
      the possibility of using high-throughput screens to aid in the design of custom
      adjuvants with unique immunological profiles to match specific mucosal vaccine
      applications. 

PMID- 25962137
TI  - eEF-2 Phosphorylation Down-Regulates P-Glycoprotein Over-Expression in Rat Brain
      Microvessel Endothelial Cells.
AB  - OBJECTIVE: We investigated whether glutamate, NMDA receptors, and eukaryote
      elongation factor-2 kinase (eEF-2K)/eEF-2 regulate P-glycoprotein expression, and
      the effects of the eEF-2K inhibitor NH125 on the expression of P-glycoprotein in
      rat brain microvessel endothelial cells (RBMECs). METHODS: Cortex was obtained
      from newborn Wistar rat brains. After surface vessels and meninges were removed,
      the pellet containing microvessels was resuspended and incubated at 37 degrees C
      in culture medium. Cell viability was assessed by the MTT assay. RBMECs were
      identified by immunohistochemistry with anti-vWF. P-glycoprotein, phospho-eEF-2,
      and eEF-2 expression were determined by western blot analysis. Mdr1a gene
      expression was analyzed by RT-PCR. RESULTS: Mdr1a mRNA, P-glycoprotein and
      phospho-eEF-2 expression increased in L-glutamate stimulated RBMECs. P
      glycoprotein and phospho-eEF-2 expression were down-regulated after NH125
      treatment in L-glutamate stimulated RBMECs. CONCLUSIONS: eEF-2K/eEF-2 should have
      played an important role in the regulation of P-glycoprotein expression in
      RBMECs. eEF-2K inhibitor NH125 could serve as an efficacious anti-multidrug
      resistant agent.

PMID- 25962138
TI  - Quantification of histone deacetylase isoforms in human frontal cortex, human
      retina, and mouse brain.
AB  - Histone deacetylase (HDAC) inhibition has promise as a therapy for Alzheimer's
      disease (AD) and other neurodegenerative diseases. Currently, therapeutic HDAC
      inhibitors target many HDAC isoforms, a particularly detrimental approach when
      HDAC isoforms are known to have different and specialized functions. We have
      developed a multiple reaction monitoring (MRM) mass spectrometry assay using
      stable isotope-labeled QconCATs as internal standards to quantify HDAC isoforms.
      We further determined a quantitative pattern of specific HDACs expressed in
      various human and mouse neural tissues. In human AD frontal cortex, HDAC1,2
      decreased 32%, HDAC5 increased 47%, and HDAC6 increased 31% in comparison to age
      matched controls. Human neural retina concentrations of HDAC1, 2, HDAC5, HDAC6,
      and HDAC7 decreased in age-related macular degeneration (AMD)-affected donors and
      exhibited a greater decrease in AD-affected donors in comparison to age-matched
      control neural retinas. Additionally, HDAC concentrations were measured in whole
      hemisphere of brain of 5XFAD mice, a model of beta-amyloid deposition, to assess
      similarity to AD in human frontal cortex. HDAC profiles of human frontal cortex
      and mouse hemisphere had noticeable differences and relatively high
      concentrations of HDAC3 and HDAC4 in mice, which were undetectable in humans. Our
      method for quantification of HDAC isoforms is a practical and efficient technique
      to quantify isoforms in various tissues and diseases. Changes in HDAC
      concentrations reported herein contribute to the understanding of the pathology
      of neurodegeneration. 

PMID- 25962139
TI  - Expression profiling of human basophils: modulation by cytokines and
      secretagogues.
AB  - Human basophils are an accessible participant of the human allergic reaction.
      There is natural variation in various functional endpoints and in signaling
      molecule expression but there has been only a limited effort to place this
      information in the context of mRNA expression profiles. This study examined the
      hypothesis that unique mRNA signatures could be identified during the response of
      human basophils to several known forms of stimulation. Highly purified human
      basophils were cultured in vitro and exposed to IL-3, IL-5, NGF, IL-33, IL-2,
      anti-IgE Ab, or FMLP and the mRNA profiles examined by microarrays. The response
      to IL-3 and anti-IgE Ab were examined on 2-3 time frames and the response to IL-3
      examined at several concentrations. In addition, the mRNA signatures of 3
      different potential phenotypes were examined. These included basophils with the
      so-called non-releaser phenotype, and basophils from atopic and non-atopic
      subjects. Given the role of IL-3 in basophil maturation and the known profound
      effects on mature basophil function, it was not surprising that IL-3 showed the
      greatest influence on the basophil transcriptome. However, it also became
      apparent that the act of isolating and culturing basophils was sufficient to
      induce a large number of changes in the transcriptome, despite high viability and
      recovery. These "culture-effect" changes dominated the changes in mRNA profiles
      induced by other stimuli. Unique signatures for anti-IgE antibody and IL-33 could
      be identified although the number of gene transcripts (6-30) that were unique to
      these two stimuli was very limited. There were no apparent unique profiles for IL
      5, NGF, IL-2 or FMLP. Therefore, a potential tool for screening basophil
      phenotypes was limited to changes that could be induced by IL-3 (or no IL-3), IL
      33 and anti-IgE Ab. 

PMID- 25962140
TI  - Temporary dietary iron restriction affects the process of thrombus resolution in
      a rat model of deep vein thrombosis.
AB  - BACKGROUND: Deep vein thrombosis (DVT) is a major cause of pulmonary
      thromboembolism and sudden death. Thus, it is important to consider the
      pathophysiology of DVT. Recently, iron has been reported to be associated with
      thrombotic diseases. Hence, in this study, we investigate the effects of dietary
      iron restriction on the process of thrombus resolution in a rat model of DVT.
      METHODS: We induced DVT in 8-week-old male Sprague-Dawley rats by performing
      ligations of their inferior venae cavae. The rats were then given either a normal
      diet (DVT group) or an iron-restricted diet (DVT+IR group). Thrombosed inferior
      venae cavae were harvested at 5 days after ligation. RESULTS: The iron-restricted
      diet reduced venous thrombus size compared to the normal diet. Intrathrombotic
      collagen content was diminished in the DVT+IR group compared to the DVT group. In
      addition, intrathrombotic gene expression and the activity of matrix
      metalloproteinase-9 were increased in the DVT+IR group compared to the DVT group.
      Furthermore, the DVT+IR group had greater intrathrombotic neovascularization as
      well as higher gene expression levels of urokinase-type plasminogen activator and
      tissue-type plasminogen activator than the DVT group. The iron-restricted diet
      decreased intrathrombotic superoxide production compared to the normal diet.
      CONCLUSIONS: These results suggest that dietary iron restriction affects the
      process of thrombus resolution in DVT.

PMID- 25962141
TI  - Human-assisted invasions of pacific islands by litoria frogs: a case study of the
      bleating tree frog on Lord Howe Island.
AB  - There are substantial differences among taxonomic groups in their capacity to
      reach remote oceanic islands via long-distance overwater dispersal from mainland
      regions. Due to their permeable skin and intolerance of saltwater, amphibians
      generally require human-assisted dispersal to reach oceanic islands. Several
      Litoria frog species have been introduced to remote islands throughout the
      Pacific Ocean region. Lord Howe Island (LHI) is an oceanic island that lies
      approximately 600 km east of the Australian mainland and has a diverse, endemic
      biota. The bleating tree frog (Litoria dentata) is native to mainland eastern
      Australia, but was accidentally introduced to LHI in the 1990s, yet its ecology
      and potential impact on LHI has remained unstudied. We used a mitochondrial
      phylogeographical approach to determine that L. dentata was introduced from the
      Ballina region in northeastern New South Wales. The founding population was
      likely accidentally introduced with cargo shipped from the mainland. We also
      completed the first detailed investigation of the distribution, ecology and
      habitat use of L. dentata on LHI. The species is widespread on LHI and is
      prevalent in human habitat, cattle pasture and undisturbed forest. We discuss the
      potential impact of introduced Litoria species on Pacific islands and outline
      what biosecurity protocols could be implemented to prevent the introduction of
      further amphibian species to the ecologically sensitive oceanic area. 

PMID- 25962142
TI  - Transfection of Babesia bovis by Double Selection with WR99210 and Blasticidin-S
      and Its Application for Functional Analysis of Thioredoxin Peroxidase-1.
AB  - Genetic manipulation is an essential technique to analyze gene function; however,
      limited methods are available for Babesia bovis, a causative pathogen of the
      globally important cattle disease, bovine babesiosis. To date, two stable
      transfection systems have been developed for B. bovis, using selectable markers
      blasticidin-S deaminase (bsd) or human dihydrofolate reductase (hdhfr). In this
      work, we combine these two selectable markers in a sequential transfection
      system. Specifically, a parent transgenic B. bovis line which episomally
      expresses green fluorescent protein (GFP) and human dihydrofolate reductase
      (hDHFR), was transfected with a plasmid encoding a fusion protein consisting of
      red fluorescent protein (RFP) and blasticidin-S deaminase (BSD). Selection with
      WR99210 and blasticidin-S resulted in the emergence of parasites double positive
      for GFP and RFP. We then applied this method to complement gene function in a
      parasite line in which thioredoxin peroxidase-1 (Bbtpx-1) gene was knocked out
      using hDHFR as a selectable marker. A plasmid was constructed harboring both RFP
      BSD and Bbtpx-1 expression cassettes, and transfected into a Bbtpx-1 knockout
      (KO) parasite. Transfectants were independently obtained by two transfection
      methods, episomal transfection and genome integration. Complementation of Bbtpx-1
      resulted in full recovery of resistance to nitrosative stress, via the nitric
      oxide donor sodium nitroprusside, which was impaired in the Bbtpx-1 KO parasites.
      In conclusion, we developed a sequential transfection method in B. bovis and
      subsequently applied this technique in a gene complementation study. This method
      will enable broader genetic manipulation of Babesia toward enhancing our
      understanding of the biology of this parasite. 

PMID- 25962143
TI  - Bone Marrow Recovery by Morphometry during Induction Chemotherapy for Acute
      Lymphoblastic Leukemia in Children.
AB  - Bone marrow architecture is grossly distorted at the diagnosis of ALL and details
      of the morphological changes that accompany response to Induction chemotherapy
      have not been reported before. While marrow aspirates are widely used to assess
      initial response to ALL therapy and provide some indications, we have enumerated
      marrow components using morphometric analysis of trephine samples with the aim of
      achieving a greater understanding of changes in bone marrow niches. Morphometric
      analyses were carried out in the bone marrow trephine samples of 44 children with
      ALL, using a NanoZoomer HT digital scanner. Diagnostic samples were compared to
      those of 32 control patients with solid tumors but without marrow involvement.
      Samples from patients with ALL had significantly increased fibrosis and the area
      occupied by bony trabeculae was lower than in controls. Cellularity was higher in
      ALL samples due to leukemic infiltration while the percentage of normal elements
      such as megakaryocytes, adipocytes, osteoblasts and osteoclasts were all
      significantly lower. During the course of Induction therapy, there was a decrease
      in the cellularity of ALL samples at day 15 of therapy with a further decrease at
      the end of Induction and an increase in the area occupied by adipocytes and the
      width of sinusoids. Reticulin fibrosis decreased throughout Induction.
      Megakaryocytes increased, osteoblasts and osteoclasts remained unchanged. No
      correlation was found between clinical presentation, early response to treatment
      and morphological changes. Our results provide a morphological background to
      further studies of bone marrow stroma in ALL. 

PMID- 25962144
TI  - Telomerase activity and telomere length in Daphnia.
AB  - Telomeres, comprised of short repetitive sequences, are essential for genome
      stability and have been studied in relation to cellular senescence and aging.
      Telomerase, the enzyme that adds telomeric repeats to chromosome ends, is
      essential for maintaining the overall telomere length. A lack of telomerase
      activity in mammalian somatic cells results in progressive shortening of
      telomeres with each cellular replication event. Mammals exhibit high rates of
      cell proliferation during embryonic and juvenile stages but very little somatic
      cell proliferation occurs during adult and senescent stages. The telomere
      hypothesis of cellular aging states that telomeres serve as an internal mitotic
      clock and telomere length erosion leads to cellular senescence and eventual cell
      death. In this report, we have examined telomerase activity, processivity, and
      telomere length in Daphnia, an organism that grows continuously throughout its
      life. Similar to insects, Daphnia telomeric repeat sequence was determined to be
      TTAGG and telomerase products with five-nucleotide periodicity were generated in
      the telomerase activity assay. We investigated telomerase function and telomere
      lengths in two closely related ecotypes of Daphnia with divergent lifespans,
      short-lived D. pulex and long-lived D. pulicaria. Our results indicate that there
      is no age-dependent decline in telomere length, telomerase activity, or
      processivity in short-lived D. pulex. On the contrary, a significant age
      dependent decline in telomere length, telomerase activity and processivity is
      observed during life span in long-lived D. pulicaria. While providing the first
      report on characterization of Daphnia telomeres and telomerase activity, our
      results also indicate that mechanisms other than telomere shortening may be
      responsible for the strikingly short life span of D. pulex. 

PMID- 25962145
TI  - Pathogenicity of Highly Pathogenic Avian Influenza Virus H5N1 in Naturally
      Infected Poultry in Egypt.
AB  - Highly pathogenic avian influenza virus (HPAIV) H5N1 has been endemic in Egypt
      since 2006, and there is increasing concern for its potential to become highly
      transmissible among humans. Infection by HPAIV H5N1 has been described in
      experimentally challenged birds. However, the pathogenicity of the H5N1 isolated
      in Egypt has never been reported in naturally infected chickens and ducks. Here
      we report a 2013 outbreak of HPAIV H5N1 in commercial poultry farms and backyards
      in Sharkia Province, Egypt. The main symptoms were ecchymosis on the shanks and
      feet, cyanosis of the comb and wattles, subcutaneous edema of the head and neck
      for chickens, and nervous signs (torticollis) for ducks. Within 48-72 hrs of the
      onset of illness, the average mortality rates were 22.8-30% and 28.5-40% in
      vaccinated chickens and non-vaccinated ducks, respectively. Tissue samples of
      chickens and ducks were collected for analyses with cross-section
      immunohistochemistry and real-time RT-PCR for specific viral RNA transcripts.
      While viral RNA was detected in nearly all tissues and sera collected, viral
      nucleoprotein was detected almost ubiquitously in all tissues, including testis.
      Interestingly, viral antigen was also observed in endothelial cells of most
      organs in chickens, and clearly detected in the trachea and brain in particular.
      Viral nucleoprotein was also detected in mononuclear cells of various organs,
      especially pulmonary tissue. We performed phylogenetic analyses and compared the
      genomic sequences of the hemagglutinin (HA) and nonstructural proteins (NS) among
      the isolated viruses, the HPAIV circulated in Egypt in the past and currently,
      and some available vaccine strains. Further analysis of deduced amino acids of
      both HA and NS1 revealed that our isolates carried molecular determinants of
      HPAIV, including the multibasic amino acids (PQGERRRK/KR*GLF) in the cleavage
      site in HA and glutamate at position 92 (D92E) in NS1. This is the first report
      of the pathogenicity of the HPAIVH5N1 strain currently circulating in naturally
      infected poultry in Egypt, which may provide unique insights into the viral
      pathogenesis in HPAIV-infected chickens and ducks. 

PMID- 25962146
TI  - Understanding the role of dicer in astrocyte development.
AB  - The Dicer1 allele is used to show that microRNAs (miRNAs) play important roles in
      astrocyte development and functions. While it is known that astrocytes that lack
      miRNAs are dysregulated, the in vivo phenotypes of these astrocytes are not well
      understood. In this study, we use Aldh1l1-EGFP transgene, a marker of astrocytes,
      to characterize mouse models with conditional Dicer1 ablation (via either human
      or mouse GFAP-Cre). This transgene revealed novel features of the defective
      astrocytes from the absence of miRNA. Although astrocyte miRNAs were depleted in
      both lines, we found histological and molecular differences in the Aldh1l1-EGFP
      cells between the two Cre lines. Aldh1l1-EGFP cells from hGFAP-Cre mutant lines
      displayed up-regulation of Aldh1l1-EGFP with increased proliferation and a
      genomic profile that acquired many features of wildtype primary astrocyte
      cultures. In the young mGFAP-Cre mutant lines we found that Aldh1l1-EGFP cells
      were disorganized and hyperproliferative in the developing cerebellum. Using the
      Aldh1l1-EGFP transgene, our work provides new insights into the roles of miRNAs
      in astrocyte development and the features of astrocytes in these two mouse
      models. 

PMID- 25962148
TI  - Risk of Neuropathy Among 28,232 Patients With Biopsy-Verified Celiac Disease.
AB  - IMPORTANCE: Earlier research on celiac disease (CD) and neuropathy has been
      hampered by the use of inpatient data, low study power, and lack of neuropathic
      characteristics. OBJECTIVE: To examine the relative risk and absolute risk of
      developing neuropathy in a nationwide population-based sample of patients with
      biopsy-verified CD. DESIGN, SETTING, AND PARTICIPANTS: Between October 27, 2006,
      and February 12, 2008, we collected data on small-intestinal biopsies performed
      at Sweden's 28 pathology departments between June 16, 1969, and February 4, 2008.
      We compared the risk of neuropathy in 28,232 patients with CD (villous atrophy,
      Marsh 3) with that of 139,473 age- and sex-matched controls. Cox proportional
      hazards regression estimated hazard ratios (HRs) and 95% CIs for neuropathy
      defined according to relevant International Classification of Diseases codes in
      the Swedish National Patient Register (consisting of both inpatient and
      outpatient data). MAIN OUTCOMES AND MEASURES: Neuropathy in patients with biopsy
      verified CD. RESULTS: Celiac disease was associated with a 2.5-fold increased
      risk of later neuropathy (95% CI, 2.1-3.0; P < .001). We also found an increased
      risk (with results reported as HRs [95% CIs]) of chronic inflammatory
      demyelinating neuropathy (2.8; 1.6-5.1; P = .001), autonomic neuropathy (4.2; 1.4
      12.3; P = .009), and mononeuritis multiplex (7.6; 1.8-32.4; P = .006), but no
      association between CD and acute inflammatory demyelinating polyneuropathy (0.8;
      0.3-2.1; P = .68). CONCLUSIONS AND RELEVANCE: We found an increased risk of
      neuropathy in patients with CD. This statistically significant association in a
      population-based sample suggests that CD screening should be completed in
      patients with neuropathy.

PMID- 25962147
TI  - Sodium salicylate suppresses GABAergic inhibitory activity in neurons of rodent
      dorsal raphe nucleus.
AB  - Sodium salicylate (NaSal), a tinnitus inducing agent, can activate serotonergic
      (5-HTergic) neurons in the dorsal raphe nucleus (DRN) and can increase serotonin
      (5-HT) level in the inferior colliculus and the auditory cortex in rodents. To
      explore the underlying neural mechanisms, we first examined effects of NaSal on
      neuronal intrinsic properties and the inhibitory synaptic transmissions in DRN
      slices of rats by using whole-cell patch-clamp technique. We found that NaSal
      hyperpolarized the resting membrane potential, decreased the input resistance,
      and suppressed spontaneous and current-evoked firing in GABAergic neurons, but
      not in 5-HTergic neurons. In addition, NaSal reduced GABAergic spontaneous and
      miniature inhibitory postsynaptic currents in 5-HTergic neurons. We next examined
      whether the observed depression of GABAergic activity would cause an increase in
      the excitability of 5-HTergic neurons using optogenetic technique in DRN slices
      of the transgenic mouse with channelrhodopsin-2 expressed in GABAergic neurons.
      When the GABAergic inhibition was enhanced by optical stimulation to GABAergic
      neurons in mouse DRN, NaSal significantly depolarized the resting membrane
      potential, increased the input resistance and increased current-evoked firing of
      5-HTergic neurons. However, NaSal would fail to increase the excitability of 5
      HTergic neurons when the GABAergic synaptic transmission was blocked by
      picrotoxin, a GABA receptor antagonist. Our results indicate that NaSal
      suppresses the GABAergic activities to raise the excitability of local 5-HTergic
      neural circuits in the DRN, which may contribute to the elevated 5-HT level by
      NaSal in the brain. 

PMID- 25962149
TI  - Recent Origin of the Methacrylate Redox System in Geobacter sulfurreducens AM-1
      through Horizontal Gene Transfer.
AB  - The origin and evolution of novel biochemical functions remains one of the key
      questions in molecular evolution. We study recently emerged methacrylate
      reductase function that is thought to have emerged in the last century and
      reported in Geobacter sulfurreducens strain AM-1. We report the sequence and
      study the evolution of the operon coding for the flavin-containing methacrylate
      reductase (Mrd) and tetraheme cytochrome s (Mcc) in the genome of G.
      sulfurreducens AM-1. Different types of signal peptides in functionally
      interlinked proteins Mrd and Mcc suggest a possible complex mechanism of
      biogenesis for chromoproteids of the methacrylate redox system. The homologs of
      the Mrd and Mcc sequence found in delta-Proteobacteria and Deferribacteres are
      also organized into an operon and their phylogenetic distribution suggested that
      these two genes tend to be horizontally transferred together. Specifically, the
      mrd and mcc genes from G. sulfurreducens AM-1 are not monophyletic with any of
      the homologs found in other Geobacter genomes. The acquisition of methacrylate
      reductase function by G. sulfurreducens AM-1 appears linked to a horizontal gene
      transfer event. However, the new function of the products of mrd and mcc may have
      evolved either prior or subsequent to their acquisition by G. sulfurreducens AM
      1. 

PMID- 25962150
TI  - Correlation between Serum Level of Monocyte Chemoattractant Protein-1 and
      Postoperative Recurrence of Spinal Tuberculosis in the Chinese Han Population.
AB  - OBJECTIVE: To correlate serum level of monocyte chemoattractant protein-1 (MCP-1)
      with postoperative recurrence of spinal tuberculosis in the Chinese Han
      population. METHODS: Patients of Han nationality with newly diagnosed spinal
      tuberculosis were consecutively included in this study. At different time points
      postoperatively, serum level of MCP-1 was determined using an enzyme linked
      immunosorbent assay. Recurrence of spinal tuberculosis after surgery and during
      the follow-up period was recorded. The correlation between serum MCP-1 level and
      recurrence of spinal tuberculosis was analyzed. RESULTS: A total of 169 patients
      with spinal tuberculosis were included in the study and followed up for an
      average of 2.2 +/- 1.3 years (range, 1-5 years). Of these patients, 11 had
      postoperative recurrence of spinal tuberculosis. The patients' serum level of MCP
      1 increased significantly after postoperative recurrence of spinal tuberculosis.
      Once the symptoms of recurrence were cured, the serum level of MCP-1 decreased
      significantly and it did not differ from patients without disease recurrence.
      CONCLUSION: Postoperative recurrence of spinal tuberculosis is likely to increase
      the serum level of MCP-1.

PMID- 25962152
TI  - Concentrated assemblies of magnetic nanoparticles in ionic liquids.
AB  - Maghemite (gamma-Fe2O3) nanoparticles (NPs) can be successfully dispersed in a
      protic ionic liquid, ethylammonium nitrate (EAN), by transfer from aqueous
      dispersions into EAN. As the aqueous systems are well controlled, several
      parameters can be tuned. Their crucial role towards the interparticle potential
      and the structure of the dispersions is evidenced: (i) the size of the NPs tunes
      the interparticle attraction monitoring dispersions to be either monophasic or
      gas-liquid-like phase separated; (ii) the nature of the initial counterion in
      water (here sodium, lithium or ethylammonium) and the amount of added water (<20
      vol%) modulate the interparticle repulsion. Very concentrated dispersions with a
      volume fraction of around 25% are obtained thanks to the gas-liquid-like phase
      separations. Such conclusions are derived from a fine structural and dynamical
      study of the dispersions on a large range of spatial scales by coupling several
      techniques: chemical analyses, optical microscopy, dynamic light scattering,
      magneto-optic birefringence and small angle scattering. 

PMID- 25962151
TI  - The impact of hypnotic suggestions on reaction times in continuous performance
      test in adults with ADHD and healthy controls.
AB  - Attention is one of the key factors in both hypnotic processes and patients with
      ADHD. In addition, the brain areas associated with hypnosis and ADHD overlap in
      many respects. However, the use of hypnosis in ADHD patients has still received
      only minor attention in research. The main purpose of the present work was to
      investigate whether hypnosis and hypnotic suggestions influence the performance
      of adult ADHD (n = 27) and control participants (n = 31) in the continuous
      performance test (CPT). The hypnotic susceptibility of the participants was
      measured by the Harvard Group Scale of Hypnotic Susceptibility (HGSHS:A) and the
      attentional task was a three minute long auditory version of the CPT. The CPT
      task was administered four times: before hypnosis (CPT1), after a hypnotic
      induction (CPT2), after suggestions about speed and accuracy (CPT3), and after
      the termination of hypnosis (CPT4). The susceptibility of the groups measured by
      HGSHS:A did not differ. There was a statistically significant decrease in
      reaction times in both ADHD and control groups between CPT2 and CPT3. The
      differences between CPT1 and CPT2, even though non-significant, were different in
      the two groups: in the ADHD group reaction times decreased whereas in the control
      group they increased. Both groups made very few errors in the short CPT. This
      study indicates that hypnotic suggestions have an effect on reaction times in the
      sustained attention task both in adult ADHD patients and control subjects. The
      theoretical and clinical implications are discussed. 

PMID- 25962154
TI  - Downregulation of notch signaling pathway in late preterm and term placentas from
      pregnancies complicated by preeclampsia.
AB  - Preeclampsia (PE) is a major cause of maternal mortality and morbidity, affecting
      3-5% of all pregnancies. The Notch signaling pathway plays an important role
      during placental development, activating several target genes. Defects in the
      Notch pathway have adverse effect on placentation. The aim of this study was to
      investigate the expression of receptors NOTCH1,-2,-3,-4, ligands DLL1,-3,-4,
      JAG1,-2 and target genes HEY1,-2 in placental tissue samples from 20 late preterm
      or term pregnancies complicated by PE versus 20 normal pregnancies. mRNA levels
      of the studied molecules were measured by quantitative Real-Time PCR (qRT-PCR),
      while the protein expression of the intracellular domain of NOTCH2 (NICD2) and
      NOTCH3 (NICD3) was measured by Western Blot (WB). qRT-PCR analysis revealed that
      NOTCH1, NOTCH4 and DLL1 were not expressed in the placenta. On the contrary,
      NOTCH2, NOTCH3, DLL3, DLL4, JAG1, JAG2, HEY1 and HEY2 mRNA levels were
      downregulated in PE samples vs. controls (p<0.01). WB confirmed that NICD2 (p =
      0.014) and NICD3 (p<0.001) protein levels were also lower in PE specimens.
      Statistical analysis revealed several significant associations: of NOTCH3 mRNA
      expression with smoking during pregnancy (p = 0.029), of NICD3 protein levels (p
      = 0.028) and DLL3 mRNA levels (p = 0.041) with birth weight centile, and of HEY2
      transcript levels with parity (p = 0.034) and mode of delivery (p = 0.028). Our
      results suggest that Notch pathway downregulation is associated with PE. Further
      studies are required in order to determine the role of these molecules in PE
      pathogenesis and to evaluate their potential use for the early detection and
      treatment of PE. 

PMID- 25962155
TI  - Conventional chemotherapy and oncogenic pathway targeting in ovarian
      carcinosarcoma using a patient-derived tumorgraft.
AB  - Ovarian carcinosarcoma is a rare subtype of ovarian cancer with poor clinical
      outcomes. The low incidence of this disease makes accrual to large clinical
      trials challenging. However, studies have shown that treatment responses in
      patient-derived xenograft (PDX) models correlate with matched-patient responses
      in the clinic, supporting their use for preclinical testing of standard and novel
      therapies. An ovarian carcinosarcoma PDX is presented herein and showed
      resistance to carboplatin and paclitaxel (similar to the patient) but exhibited
      significant sensitivity to ifosfamide and paclitaxel. The PDX demonstrated
      overexpression of EGFR mRNA and gene amplification by array comparative genomic
      hybridization (log2 ratio 0.399). EGFR phosphorylation was also detected.
      Angiogensis and insulin-like growth factor pathways were also implicated by
      overexpression of VEGFC and IRS1. In order to improve response to chemotherapy,
      the PDX was treated with carboplatin/paclitaxel with or without a pan-HER and
      VEGF inhibitor (BMS-690514) but there was no tumor growth inhibition or improved
      animal survival, which may be explained by a KRAS mutation. Resistance was also
      observed when the IGF-1R inhibitor BMS-754807 was combined with
      carboplatin/paclitaxel. Because poly (ADP-ribose) polymerase inhibitors have
      activity in ovarian cancer patients, with and without BRCA mutations, ABT-888 was
      also tested but found to have no activity. Pathogenic mutations were also
      detected in TP53 and PIK3CA. In conclusion, ifosfamide/paclitaxel was superior to
      carboplatin/paclitaxel in this ovarian carcinosarcoma PDX and gene overexpression
      or amplification alone was not sufficient to predict response to targeted
      therapy. Better predictive markers of response are needed. 

PMID- 25962156
TI  - 4-1BB Signaling Enhances Primary and Secondary Population Expansion of CD8+ T
      Cells by Maximizing Autocrine IL-2/IL-2 Receptor Signaling.
AB  - 4-1BB (CD137), a member of the tumor necrosis factor receptor superfamily
      (TNFRSF), is primarily expressed on activated T cells and is known to enhance
      proliferation of T cells, prevent activation-induced cell death, and promote
      memory formation of CD8+ T cells. In particular, it is well acknowledged that 4
      1BB triggering preferentially enhances the expansion of CD8+ T cells rather than
      CD4+ T cells, but the underlying mechanism remains unclear. Here we found that 4
      1BB triggering markedly increased IL-2Ralpha (CD25) and IL-2 expressions of CD8+
      T cells but minimally for CD4+ T cells. Proliferation of CD8+ T cells was
      moderately enhanced by direct 4-1BB triggering in the absence of signaling
      through IL-2Ralpha/IL-2 interactions, but further promoted in the presence of IL
      2Ralpha/IL-2 interactions. Among the TNFRSF members including OX40, GITR, CD30,
      and CD27, 4-1BB was superior in the ability to induce IL-2Ralpha expression on
      CD8+ T cells. When the primary and secondary expansions of CD8+ T cells in vivo
      were examined by adoptively transferring OVA-specific CD8+ T cells along with the
      treatment with agonistic anti-4-1BB and/or antagonistic anti-CD25 F(ab')2 mAb, 4
      1BB triggering enhanced both primary and secondary expansion of CD8+ T cells in
      vivo, and the 4-1BB effects were moderately suppressed in primary expansion while
      completely abolished in secondary expansion of OVA-specific CD8+ T cells by
      blocking IL-2Ralpha. These results suggest that 4-1BB-mediated increases of IL
      2Ralpha and IL-2 prolong the effects of transient TCR- and 4-1BB-mediated
      signaling in CD8+ T cells, and that 4-1BB triggering preferentially enhances the
      expansion of CD8+ T cells through the amplification of autocrine IL-2/IL-2R
      signaling loop. 

PMID- 25962157
TI  - An alternative approach for estimating the accuracy of colposcopy in detecting
      cervical precancer.
AB  - INTRODUCTION: Since colposcopy helps to detect cervical cancer in its
      precancerous stages, as new strategies and technologies are developed for the
      clinical management of cervical neoplasia, precisely determining the accuracy of
      colposcopy is important for characterizing its continued role. Our objective was
      to employ a more precise methodology to estimate of the accuracy of colposcopy to
      better reflect clinical practice. STUDY DESIGN: For each patient, we compared the
      worst histology result among colposcopically positive sites to the worst
      histology result among all sites biopsied, thereby more accurately determining
      the number of patients that would have been underdiagnosed by colposcopy than
      previously estimated. MATERIALS AND METHODS: We utilized data from a clinical
      trial in which 850 diagnostic patients had been enrolled. Seven hundred and
      ninety-eight of the 850 patients had been examined by colposcopy, and biopsy
      samples were taken at colposcopically normal and abnormal sites. Our endpoints of
      interest were the percentages of patients underdiagnosed, and sensitivity and
      specificity of colposcopy. RESULTS: With the threshold of low-grade squamous
      intraepithelial lesions for positive colposcopy and histology diagnoses, the
      sensitivity of colposcopy decreased from our previous assessment of 87.0% to
      74.0%, while specificity remained the same. The drop in sensitivity was the
      result of histologically positive sites that were diagnosed as negative by
      colposcopy. Thus, 28.4% of the 798 patients in this diagnostic group would have
      had their condition underdiagnosed by colposcopy in the clinic. CONCLUSIONS: In
      utilizing biopsies at multiple sites of the cervix, we present a more precise
      methodology for determining the accuracy of colposcopy. The true accuracy of
      colposcopy is lower than previously estimated. Nevertheless, our results
      reinforce previous conclusions that colposcopy has an important role in the
      diagnosis of cervical precancer.

PMID- 25962158
TI  - Ample Evidence: Dehydroepiandrosterone (DHEA) Conversion into Activated Steroid
      Hormones Occurs in Adrenal and Ovary in Female Rat.
AB  - Dehydroepiandrosterone (DHEA) is important for human health, especially for
      women. All estrogens and practically half of androgens are synthesized from DHEA
      in peripheral tissues. However, the mechanism and exact target tissues of DHEA
      biotransformation in the female are not fully clear. The present study showed
      that maximal content of androstenedione (AD) and testosterone (T) were observed
      at 3h after DHEA administration in female rats, which was 264% and 8000% above
      the control, respectively. Estradiol (E2) content significantly increased at 6h
      after DHEA administration, which was 113% higher than that in control group.
      Gavage with DHEA could significantly reduce 3beta-hydroxysteroid dehydrogenase
      (3beta-HSD) mRNA level at 3-12h and 17beta-hydroxysteroid dehydrogenase (17beta
      HSD) mRNA level at 12h in ovary, while increasing aromatase mRNA levels at 6, 24,
      and 48 h. It is interesting that administration of DHEA caused a significant
      increase of 17beta-HSD, 3beta-HSD and aromatase mRNA levels in adrenal. The AD
      and T contents also markedly increased by 537% and 2737% after DHEA
      administration in ovariectomised rats, in company with a significant increase in
      17beta-HSD and 3beta-HSD mRNA levels and decreased aromatase mRNA level in
      adrenal. However, DHEA administration did not restore the decreased E2, estrone
      (E1), and progesterone (P) caused by the removal of the ovaries in females. These
      results clearly illustrated that exogenous DHEA is preferentially converted into
      androgens in adrenal, while its conversion to estrogens mainly happens in the
      ovary through steroidogenic enzyme in female rats.

PMID- 25962159
TI  - An ShRNA Based Genetic Screen Identified Sesn2 as a Potential Tumor Suppressor in
      Lung Cancer via Suppression of Akt-mTOR-p70S6K Signaling.
AB  - BACKGROUND: Lung cancer is emerging rapidly as the leading death cause in Chinese
      cancer patients. The causal factors for Chinese lung cancer development remain
      largely unclear. Here we employed an shRNA library-based loss-of-function screen
      in a genome-wide and unbiased manner to interrogate potential tumor suppressor
      candidates in the immortalized human lung epithelial cell line BEAS-2B.
      METHODS/RESULTS: Soft agar assays were conducted for screening BEAS-2B cells
      infected with the retroviral shRNA library with the acquired feature of anchorage
      independent growth, large (>0.5mm in diameter) and well-separated colonies were
      isolated for proliferation. PCRs were performed to amplify the integrated shRNA
      fragment from individual genomic DNA extracted from each colony, and each PCR
      product is submitted for DNA sequencing to reveal the integrated shRNA and its
      target gene. A total of 6 candidate transformation suppressors including INPP4B,
      Sesn2, TIAR, ACRC, Nup210, LMTK3 were identified. We validated Sesn2 as the
      candidate of lung cancer tumor suppressor. Knockdown of Sesn2 by an shRNA
      targeting 3' UTR of Sesn2 transcript potently stimulated the proliferation and
      malignant transformation of lung bronchial epithelial cell BEAS-2B via activation
      of Akt-mTOR-p70S6K signaling, whereas ectopic expression of Sens2 re-suppressed
      the malignant transformation elicited by the Sesn2 shRNA. Moreover, knockdown of
      Sesn2 in BEAS-2B cells promoted the BEAS-2B cell-transplanted xenograft tumor
      growth in nude mice. Lastly, DNA sequencing indicated mutations of Sesn2 gene are
      rare, the protein levels of Sesn2 of 77 Chinese lung cancer patients varies
      greatly compared to their adjacent normal tissues, and the low expression level
      of Sesn2 associates with the poor survival in these examined patients by Kaplan
      Meier analysis. CONCLUSIONS: Our shRNA-based screen has demonstrated Sesn2 is a
      potential tumor suppressor in lung epithelial cells. The expression level of
      Sesn2 may serve as a prognostic marker for Chinese lung cancer patients in the
      clinic.

PMID- 25962160
TI  - The Spread of Aedes albopictus in Metropolitan France: Contribution of
      Environmental Drivers and Human Activities and Predictions for a Near Future.
AB  - Invasion of new territories by insect vector species that can transmit pathogens
      is one of the most important threats for human health. The spread of the mosquito
      Aedes albopictus in Europe is emblematic, because of its major role in the
      emergence and transmission of arboviruses such as dengue or chikungunya. Here, we
      modeled the spread of this mosquito species in France through a statistical
      framework taking advantage of a long-term surveillance dataset going back to the
      first observation of Ae. albopictus in the Metropolitan area. After validating
      the model, we show that human activities are especially important for mosquito
      dispersion while land use is a major factor for mosquito establishment. More
      importantly, we show that Ae. albopictus invasion is accelerating through time in
      this area, resulting in a geographic range extending further and further year
      after year. We also show that sporadic "jump" of Ae. albopictus in a new location
      far from the colonized area did not succeed in starting a new invasion front so
      far. Finally, we discuss on a potential adaptation to cooler climate and the risk
      of invasion into Northern latitudes. 

PMID- 25962162
TI  - Correction: Biomass and abundance biases in European standard gillnet sampling.

PMID- 25962161
TI  - Cream formulation impact on topical administration of engineered colloidal
      nanoparticles.
AB  - In order to minimize the impact of systemic toxicity of drugs in the treatment of
      local acute and chronic inflammatory reactions, the achievement of reliable and
      efficient delivery of therapeutics in/through the skin is highly recommended.
      While the use of nanoparticles is now an established practice for drug
      intravenous targeted delivery, their transdermal penetration is still poorly
      understood and this important administration route remains almost unexplored. In
      the present study, we have synthesized magnetic (iron oxide) nanoparticles (MNP)
      coated with an amphiphilic polymer, developed a water-in-oil emulsion formulation
      for their topical administration and compared the skin penetration routes with
      the same nanoparticles deposited as a colloidal suspension. Transmission and
      scanning electron microscopies provided ultrastructural evidence that the
      amphiphilic nanoparticles (PMNP) cream formulation allowed the efficient
      penetration through all the skin layers with a controllable kinetics compared to
      suspension formulation. In addition to the preferential follicular pathway, also
      the intracellular and intercellular routes were involved. PMNP that crossed all
      skin layers were quantified by inductively coupled plasma mass spectrometry. The
      obtained data suggests that combining PMNP amphiphilic character with cream
      formulation improves the intradermal penetration of nanoparticles. While PMNP
      administration in living mice via aqueous suspension resulted in preferential
      nanoparticle capture by phagocytes and migration to draining lymph nodes, cream
      formulation favored uptake by all the analyzed dermis cell types, including
      hematopoietic and non-hematopoietic. Unlike aqueous suspension, cream formulation
      also favored the maintenance of nanoparticles in the dermal architecture avoiding
      their dispersion and migration to draining lymph nodes via afferent lymphatics. 

PMID- 25962163
TI  - Inhibition of Staphylococcus aureus Adhesion to the Surface of a Reticular
      Heavyweight Polypropylene Mesh Soaked in a Combination of Chlorhexidine and
      Allicin: An In vitro Study.
AB  - INTRODUCTION: Presoaking meshes for hernia repair with antiseptics prior to
      implantation could decrease the adhesion of microorganisms to the material
      surface and reduce the risk of antibiotic resistances. In this work, we evaluate
      chlorhexidine and allicin (natural antiseptic not yet tested for these purposes)
      against vancomycin as antiseptics to be used in the pretreatment of a heavyweight
      polypropylene mesh using an in vitro model of bacterial contamination. METHODS:
      Solutions of saline, vancomycin (40 ug/mL), allicin (1,000 ug/mL), chlorhexidine
      (2%-0.05%) and the combination allicin-chlorhexidine (900 ug/mL-0.05%) were
      analyzed with agar diffusion tests in the presence of 106 CFU Staphylococcus
      aureus ATCC25923. Additionally, sterile fragments of Surgipro (1 cm2) were soaked
      with the solutions and cultured onto contaminated agar plates for 24/48/72 h. The
      antimicrobial material DualMesh Plus was utilized as positive control. At every
      time, the inhibition zones were measured and the bacterial adhesion to the mesh
      surface quantified (sonication, scanning electron microscopy). Cytotoxicity of
      the treatments was examined (alamarBlue) using rabbit skin fibroblasts. RESULTS:
      The largest zones of inhibition were created by allicin-chlorhexidine.
      Chlorhexidine was more effective than vancomycin, and allicin lost its
      effectiveness after 24 h. No bacteria adhered to the surface of the DualMesh Plus
      or the meshes soaked with vancomycin, chlorhexidine and allicin-chlorhexidine. On
      the contrary, saline and allicin allowed adherence of high loads of bacteria.
      Vancomycin had no toxic effects on fibroblasts, while allicin and chlorhexidine
      exerted high toxicity. Cytotoxicity was significantly reduced with the allicin
      chlorhexidine combination. CONCLUSIONS: The use of antiseptics such as
      chlorhexidine, alone or combined with others like allicin, could represent an
      adequate prophylactic strategy to be used for hernia repair materials because
      soaking with these agents provides the mesh with similar antibacterial properties
      to those observed after soaking with vancomycin, similar to the effect of
      DualMesh Plus.

PMID- 25962164
TI  - Reduced regional brain cortical thickness in patients with heart failure.
AB  - AIMS: Autonomic, cognitive, and neuropsychologic deficits appear in heart failure
      (HF) subjects, and these compromised functions depend on cerebral cortex
      integrity in addition to that of subcortical and brainstem sites. Impaired
      autoregulation, low cardiac output, sleep-disordered-breathing, hypertension, and
      diabetic conditions in HF offer considerable potential to affect cortical areas
      by loss of neurons and glia, which would be expressed as reduced cortical
      thicknesses. However, except for gross descriptions of cortical volume
      loss/injury, regional cortical thickness integrity in HF is unknown. Our goal was
      to assess regional cortical thicknesses across the brain in HF, compared to
      control subjects. METHODS AND RESULTS: We examined localized cortical thicknesses
      in 35 HF and 61 control subjects with high-resolution T1-weighted images (3.0
      Tesla MRI) using FreeSurfer software, and assessed group differences with
      analysis-of-covariance (covariates; age, gender; p<0.05; FDR). Significantly
      reduced cortical thicknesses appeared in HF over controls in multiple areas,
      including the frontal, parietal, temporal, and occipital lobes, more markedly on
      the left side, within areas that control autonomic, cognitive, affective,
      language, and visual functions. CONCLUSION: Heart failure subjects show reduced
      regional cortical thicknesses in sites that control autonomic, cognitive,
      affective, language, and visual functions that are deficient in the condition.
      The findings suggest chronic tissue alterations, with regional changes reflecting
      loss of neurons and glia, and presumably are related to earlier-described axonal
      changes. The pathological mechanisms contributing to reduced cortical thicknesses
      likely include hypoxia/ischemia, accompanying impaired cerebral perfusion from
      reduced cardiac output and sleep-disordered-breathing and other comorbidities in
      HF.

PMID- 25962165
TI  - First-In-Human, Double-Blind, Placebo-Controlled, Randomized, Dose-Escalation
      Study of BG00010, a Glial Cell Line-Derived Neurotrophic Factor Family Member, in
      Subjects with Unilateral Sciatica.
AB  - OBJECTIVE: To evaluate the safety, tolerability, and pharmacokinetics of single
      doses of BG00010 (neublastin, artemin, enovin) in subjects with unilateral
      sciatica. METHODS: This was a single-center, blinded, placebo-controlled,
      randomized Phase 1 sequential-cohort, dose-escalation study (ClinicalTrials.gov
      identifier NCT00961766; funded by Biogen Idec). Adults with unilateral sciatica
      were enrolled at The Royal Adelaide Hospital, Australia. Four subjects were
      assigned to each of eleven cohorts (intravenous BG00010 0.3, 1, 3, 10, 25, 50,
      100, 200, 400, or 800 MUg/kg, or subcutaneous BG00010 50 MUg/kg) and were
      randomized 3:1 to receive a single dose of BG00010 or placebo. The primary safety
      and tolerability assessments were: adverse events; clinical laboratory parameters
      and vital signs; pain as measured by a Likert rating scale; intra-epidermal nerve
      fiber density; and longitudinal assessment of quantitative sensory test
      parameters. Blood, serum, and plasma samples were collected for pharmacokinetic
      and pharmacodynamic assessments. Subjects were blinded to treatment assignment
      throughout the study. The investigator was blinded to treatment assignment until
      the Data Safety Review Committee review of unblinded data, which occurred after
      day 28. RESULTS: Beyond the planned enrollment of 44 subjects, four additional
      subjects were enrolled into to the intravenous BG00010 200 MUg/kg cohort after
      one original subject experienced mild generalized pruritus. Therefore, a total of
      48 subjects were enrolled between August 2009 and December 2011; all were
      included in the safety analyses. BG00010 was generally well tolerated: in primary
      analyses, the most common treatment-emergent adverse events were changes in
      temperature perception, pruritus, rash, or headache; no trends were observed in
      clinical laboratory parameters, vital signs, intra-epidermal nerve fiber density,
      or quantitative sensory testing. BG00010 was not associated with any clear, dose
      dependent trends in Likert pain scores. BG00010 was rapidly distributed, with a
      prolonged terminal elimination phase. CONCLUSIONS: These data support the
      development of BG00010 for the treatment of neuropathic pain. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT00961766.

PMID- 25962166
TI  - Grouping Pentylenetetrazol-Induced Epileptic Rats According to Memory Impairment
      and MicroRNA Expression Profiles in the Hippocampus.
AB  - Previous studies have demonstrated a close relationship between abnormal
      regulation of microRNA (miRNA) and various types of diseases, including epilepsy
      and other neurological disorders of memory. However, the role of miRNA in the
      memory impairment observed in epilepsy remains unknown. In this study, a model of
      temporal lobe epilepsy (TLE) was induced via pentylenetetrazol (PTZ) kindling in
      Sprague-Dawley rats. First, the TLE rats were subjected to Morris water maze to
      identify those with memory impairment (TLE-MI) compared with TLE control rats
      (TLE-C), which presented normal memory. Both groups were analyzed to detect
      dysregulated miRNAs in the hippocampus; four up-regulated miRNAs (miR-34c, miR
      374, miR-181a, and miR-let-7c-1) and seven down-regulated miRNAs (miR-1188, miR
      770-5p, miR-127-5p, miR-375, miR-331, miR-873-5p, and miR-328a) were found. Some
      of the dysregulated miRNAs (miR-34c, miR-1188a, miR-328a, and miR-331) were
      confirmed using qRT-PCR, and their blood expression patterns were identical to
      those of their counterparts in the rat hippocampus. The targets of these
      dysregulated miRNAs and other potentially enriched biological signaling pathways
      were analyzed using bioinformatics. Following these results, the MAPK, apoptosis
      and hippocampal signaling pathways might be involved in the molecular mechanisms
      underlying the memory disorders of TLE. 

PMID- 25962168
TI  - Does the Brain Detect 3G Mobile Phone Radiation Peaks? An Explorative In-Depth
      Analysis of an Experimental Study.
AB  - This study aimed to investigate whether third generation mobile phone radiation
      peaks result in event related potentials. Thirty-one healthy females
      participated. In this single-blind, cross-over design, a 15 minute mobile phone
      exposure was compared to two 15 minute sham phone conditions, one preceding and
      one following the exposure condition. Each participant was measured on two
      separate days, where mobile phone placement was varied between the ear and heart.
      EEG activity and radiofrequency radiation were recorded jointly. Epochs of 1200
      ms, starting 200 ms before and lasting until 1000 ms after the onset of a
      radiation peak, were extracted from the exposure condition. Control epochs were
      randomly selected from the two sham phone conditions. The main a-priori
      hypothesis to be tested concerned an increase of the area in the 240-500 ms post
      stimulus interval, in the exposure session with ear-placement. Using multilevel
      regression analyses the placement*exposure interaction effect was significant for
      the frontal and central cortical regions, indicating that only in the mobile
      phone exposure with ear-placement an enlarged cortical reactivity was found. Post
      hoc analyses based on visual inspection of the ERPs showed a second significantly
      increased area between 500-1000 ms post-stimulus for almost every EEG location
      measured. It was concluded that, when a dialing mobile phone is placed on the
      ear, its radiation, although unconsciously, is electrically detected by the
      brain. The question of whether or not this cortical reactivity results in a
      negative health outcome has to be answered in future longitudinal experiments.

PMID- 25962167
TI  - Clinical and genetic factors associated with progression of geographic atrophy
      lesions in age-related macular degeneration.
AB  - Worldwide, age-related macular degeneration (AMD) is a serious threat to vision
      loss in individuals over 50 years of age with a pooled prevalence of
      approximately 9%. For 2020, the number of people afflicted with this condition is
      estimated to reach 200 million. While AMD lesions presenting as geographic
      atrophy (GA) show high inter-individual variability, only little is known about
      prognostic factors. Here, we aimed to elucidate the contribution of clinical,
      demographic and genetic factors on GA progression. Analyzing the currently
      largest dataset on GA lesion growth (N = 388), our findings suggest a significant
      and independent contribution of three factors on GA lesion growth including at
      least two genetic factors (ARMS2_rs10490924 [P < 0.00088] and C3_rs2230199 [P <
      0.00015]) as well as one clinical component (presence of GA in the fellow eye [P
      < 0.00023]). These correlations jointly explain up to 7.2% of the observed inter
      individual variance in GA lesion progression and should be considered in strategy
      planning of interventional clinical trials aimed at evaluating novel treatment
      options in advanced GA due to AMD. 

PMID- 25962169
TI  - Identification of two metallothioneins as novel inhalative coffee allergens cof a
      2 and cof a 3.
AB  - BACKGROUND: Dust of green coffee beans is known to be a relevant cause for
      occupational allergic disorders in coffee industry workers. Recently, we
      described the first coffee allergen (Cof a 1) establishing an allergenic
      potential of green coffee dust. OBJECTIVE: Our aim was to identify allergenic
      components of green coffee in order to enhance inhalative coffee allergy
      diagnosis. METHODS: A Coffea arabica pJuFo cDNA phage display library was created
      and screened for IgE binding with sera from allergic coffee workers. Two further
      coffee allergens were identified by sequence analysis, expressed in E. coli, and
      evaluated by Western blots. The prevalence of sensitization to recombinant Cof a
      1, Cof a 2, and Cof a 3 and to commercially available extract was investigated by
      ELISA (enzyme-linked immunosorbent assay) respectively CAP (capacity test)
      screening in 18 sera of symptomatic coffee workers. RESULTS: In addition to the
      previously described chitinase Cof a 1, two Coffea arabica cysteine-rich
      metallothioneins of 9 and 7 kDa were identified and included in the IUIS Allergen
      Nomenclature as Cof a 2 and Cof a 3. Serum IgE antibodies to at least one of the
      recombinant allergens were found in 8 out of 18 symptomatic coffee workers (44%).
      Only 2 of the analysed sera (11%) had reacted previously to the commercial
      allergy test. CONCLUSIONS: In addition to the previously described Cof a 1 we
      have identified two further coffee proteins to be type I coffee allergens (Cof a
      2 and Cof a 3) which may have a relevant potential for the specific diagnosis
      and/or therapy of coffee allergy.

PMID- 25962170
TI  - An Efficient Protocol for Plantlet Regeneration via Direct Organogenesis by Using
      Nodal Segments from Embryo-Cultured Seedlings of Cinnamomum camphora L.
AB  - A simple and efficient plantlet regeneration protocol via direct organogenesis
      was established for camphor tree (Cinnamomum camphora L.). Stem segments with one
      node (SN explants) from embryo-cultured seedlings (EC seedlings) were used as
      explants. Murashige and Skoog (MS) medium supplemented with 0.5 mg/L 2, 4
      dichlorophenoxyacetic acid and 2.0 mg/L 6-benzyladenine was used to induce
      cotyledonary embryo germination. This medium was also used for EC seedlings
      propagation and adventitious bud induction from SN explants. Regenerated
      plantlets were cultured on hormone-free MS medium for elongation and root
      induction. The regeneration capability of SN explants was compared by using EC
      seedling lines established in this research. EC seedling line EL6 exhibited the
      highest adventitious bud induction frequency (91.7%) and the highest number of
      buds per responding explant (5.2), which was considered as the most efficient EC
      seedling line for further gene transformation research. 

PMID- 25962171
TI  - Alcohol Consumption among HIV-Infected Persons in a Large Urban HIV Clinic in
      Kampala Uganda: A Constellation of Harmful Behaviors.
AB  - INTRODUCTION: Alcohol use by persons living with HIV/AIDS (PLWHA) negatively
      impacts the public health benefits of antiretroviral therapy (ART). Using a
      standardized alcohol assessment tool, we estimate the prevalence of alcohol use,
      identify associated factors, and test the association of alcohol misuse with
      sexual risk behaviors among PLWHA in Uganda. METHODS: A cross-section of PLWHA in
      Kampala were interviewed regarding their sexual behavior and self-reported
      alcohol consumption in the previous 6 months. Alcohol use was assessed using the
      alcohol use disorders identification test (AUDIT). Gender-stratified log binomial
      regression analyses were used to identify independent factors associated with
      alcohol misuse and to test whether alcohol misuse was associated with risky
      sexual behaviors. RESULTS: Of the 725 subjects enrolled, 235 (33%) reported any
      alcohol use and 135 (18.6%) reported alcohol misuse, while 38 (5.2%) drank
      hazardous levels of alcohol. Alcohol misuse was more likely among subjects not
      yet on ART (adjusted prevalence ratio [aPR] was 1.65 p=0.043 for males and 1.79,
      p=0.019 for females) and those with self-reported poor adherence (aPR for
      males=1.56, p=0.052, and for females=1.93, p=0.0189). Belonging to Pentecostal or
      Muslim religious denominations was protective against alcohol misuse compared to
      belonging to Anglican and Catholic denominations in both sexes (aPR=0.11 for men,
      p<0.001, and aPR=0.32 for women, p=0.003). Alcohol misuse was independently
      associated with reporting risky sexual behaviors (aPR=1.67; 95% CI: 1.07-2.60,
      p=0.023) among males, but not significant among females (aPR=1.29; 95% CI: 0.95
      1.74, p=0.098). Non-disclosure of HIV positive status to sexual partner was
      significantly associated with risky sex in both males (aPR=1.69; p=0.014) and
      females (aPR 2.45; p<0.001). CONCLUSION: Alcohol use among PLWHA was high, and
      was associated with self-reported medication non-adherence, non-disclosure of HIV
      positive status to sexual partner(s), and risky sexual behaviors among male
      subjects. Interventions targeting alcohol use and the associated negative
      behaviors should be tested in this setting.

PMID- 25962172
TI  - Branchial cilia and sperm flagella recruit distinct axonemal components.
AB  - Eukaryotic cilia and flagella have highly conserved 9 + 2 structures. They are
      functionally diverged to play cell-type-specific roles even in a multicellular
      organism. Although their structural components are therefore believed to be
      common, few studies have investigated the molecular diversity of the protein
      components of the cilia and flagella in a single organism. Here we carried out a
      proteomic analysis and compared protein components between branchial cilia and
      sperm flagella in a marine invertebrate chordate, Ciona intestinalis. Distinct
      feature of protein recruitment in branchial cilia and sperm flagella has been
      clarified; (1) Isoforms of alpha- and beta-tubulins as well as those of actins
      are distinctly used in branchial cilia or sperm flagella. (2) Structural
      components, such as dynein docking complex, tektins and an outer dense fiber
      protein, are used differently by the cilia and flagella. (3) Sperm flagella are
      specialized for the cAMP- and Ca2+-dependent regulation of outer arm dynein and
      for energy metabolism by glycolytic enzymes. Our present study clearly
      demonstrates that flagellar or ciliary proteins are properly recruited according
      to their function and stability, despite their apparent structural resemblance
      and conservation. 

PMID- 25962173
TI  - Modeling the cellular mechanisms and olfactory input underlying the triphasic
      response of moth pheromone-sensitive projection neurons.
AB  - In the antennal lobe of the noctuid moth Agrotis ipsilon, most pheromone
      sensitive projection neurons (PNs) exhibit a triphasic firing pattern of
      excitation (E1)-inhibition (I)-excitation (E2) in response to a pulse of the sex
      pheromone. To understand the mechanisms underlying this stereotypical discharge,
      we developed a biophysical model of a PN receiving inputs from olfactory receptor
      neurons (ORNs) via nicotinic cholinergic synapses. The ORN is modeled as an
      inhomogeneous Poisson process whose firing rate is a function of time and is
      fitted to extracellular data recorded in response to pheromone stimulations at
      various concentrations and durations. The PN model is based on the Hodgkin-Huxley
      formalism with realistic ionic currents whose parameters were derived from
      previous studies. Simulations revealed that the inhibitory phase I can be
      produced by a SK current (Ca2+-gated small conductance K+ current) and that the
      excitatory phase E2 can result from the long-lasting response of the ORNs.
      Parameter analysis further revealed that the ending time of E1 depends on some
      parameters of SK, Ca2+, nACh and Na+ currents; I duration mainly depends on the
      time constant of intracellular Ca2+ dynamics, conductance of Ca2+ currents and
      some parameters of nACh currents; The mean firing frequency of E1 and E2 depends
      differentially on the interaction of various currents. Thus it is likely that the
      interplay between PN intrinsic currents and feedforward synaptic currents are
      sufficient to generate the triphasic firing patterns observed in the noctuid moth
      A. ipsilon. 

PMID- 25962174
TI  - Generational and time period differences in American adolescents' religious
      orientation, 1966-2014.
AB  - In four large, nationally representative surveys (N = 11.2 million), American
      adolescents and emerging adults in the 2010s (Millennials) were significantly
      less religious than previous generations (Boomers, Generation X) at the same age.
      The data are from the Monitoring the Future studies of 12th graders (1976-2013),
      8th and 10th graders (1991-2013), and the American Freshman survey of entering
      college students (1966-2014). Although the majority of adolescents and emerging
      adults are still religiously involved, twice as many 12th graders and college
      students, and 20%-40% more 8th and 10th graders, never attend religious services.
      Twice as many 12th graders and entering college students in the 2010s (vs. the
      1960s-70s) give their religious affiliation as "none," as do 40%-50% more 8th and
      10th graders. Recent birth cohorts report less approval of religious
      organizations, are less likely to say that religion is important in their lives,
      report being less spiritual, and spend less time praying or meditating. Thus,
      declines in religious orientation reach beyond affiliation to religious
      participation and religiosity, suggesting a movement toward secularism among a
      growing minority. The declines are larger among girls, Whites, lower-SES
      individuals, and in the Northeastern U.S., very small among Blacks, and non
      existent among political conservatives. Religious affiliation is lower in years
      with more income inequality, higher median family income, higher materialism,
      more positive self-views, and lower social support. Overall, these results
      suggest that the lower religious orientation of Millennials is due to time period
      or generation, and not to age. 

PMID- 25962175
TI  - Participation of Children with Disabilities in Taiwan: The Gap between
      Independence and Frequency.
AB  - BACKGROUND: Independence and frequency are two distinct dimensions of
      participation in daily life. The gap between independence and frequency may
      reflect the role of the environment on participation, but this distinction has
      not been fully explored. METHODS: A total of 18,119 parents or primary caregivers
      of children with disabilities aged 6.0-17.9 years were interviewed in a cross
      sectional nationwide survey with the Functioning Scale of the Disability
      Evaluation System - Child version (FUNDES-Child). A section consisting of 20
      items measured the children's daily participation in 4 environmental settings:
      home, neighborhood/community, school, and home/community. Higher independence and
      frequency restriction scores indicated greater limitation of participation in
      daily activities. Scores for independence, frequency and independence-frequency
      gaps were examined across ages along with trend analysis. ANOVA was used to
      compare the gaps across settings and diagnoses for children with mild levels of
      severity of impairment. FINDINGS: A negative independence-frequency gap
      (restriction of frequency was greater than that of independence) was found for
      children with mild to severe levels of impairment. A positive gap (restriction of
      independence was greater than that of frequency) was found for children with
      profound levels of severity. The gaps became wider with age in most settings of
      children with mild impairment and different diagnoses. Widest negative gaps were
      found for the neighborhood/community settings than for the other three settings
      for children with mild to severe impairment. CONCLUSIONS: Children's
      participation and independence-frequency gaps depend not only on the severity of
      their impairments or diagnoses, but also on their age, the setting and the
      support provided by their environment. In Taiwan, more frequency restrictions
      than ability restrictions were found for children with mild to moderate severity,
      especially in the neighborhood/community setting, and increased with age. Further
      identification of environmental opportunities that positively impact frequency of
      participation is needed.

PMID- 25962176
TI  - The Influence of Antral Ulcers on Intramural Gastric Nerve Projections Supplying
      the Pyloric Sphincter in the Pig (Sus scrofa domestica)-Neuronal Tracing Studies.
AB  - BACKGROUND: Gastric ulcerations in the region of antrum pylori represent a
      serious medical problem in humans and animals. Such localization of ulcers can
      influence the intrinsic descending nerve supply to the pyloric sphincter. The
      pyloric function is precisely regulated by intrinsic and extrinsic nerves.
      Impaired neural regulation could result in pyloric sphincter dysfunction and
      gastric emptying malfunction. The aim of the study was to determine the effect of
      gastric antral ulcerations on the density and distribution of intramural gastric
      descending neurons supplying the pyloric sphincter in pigs. METHODOLOGY/PRINCIPAL
      FINDINGS: The experiment was performed on 2 groups of pigs: healthy gilts (n=6)
      and gilts with experimentally induced peptic ulcers in the region of antrum
      pylori (n=6). Gastric neurons supplying pyloric sphincter were labeled using the
      retrograde neuronal tracing technique (20MUl of Fast Blue tracer injected into
      the pyloric sphincter muscle). After a week survival period the animals were
      sacrificed and the stomachs were collected. Then, the stomach wall was cross-cut
      into 0.5cm thick sections taken in specified intervals (section I - 1.5cm;
      section II - 3.5cm; section III - 5.5cm; section IV - 7.5cm) starting from the
      sphincter. Consecutive microscopic slices prepared from each section were
      analyzed under fluorescent microscope to count traced neurons. Obtained data were
      statistically analyzed. The total number of FB-positive perikarya observed within
      all studied sections significantly decreased from 903.3 +/- 130.7 in control to
      243.8 +/- 67.3 in experimental animals. In healthy pigs 76.1 +/- 6.7% of labeled
      neurons were observed within the section I, 23.53 +/- 6.5% in section II and only
      occasional cells in section III. In experimental animals, as many as 93.8 +/-
      2.1% of labeled cells were observed within the section I and only 6.2 +/- 2.2% in
      section II, while section III was devoid of such neurons. There were no traced
      perikarya in section IV observed in both groups of pigs.
      CONCLUSIONS/SIGNIFICANCE: Obtained results revealed for the first time
      significant impact of antral ulcerations on intramural descending nerve pathways
      supplying the pyloric sphincter in pigs, animals of increasing value in
      biomedical research and great economic importance.

PMID- 25962177
TI  - Systematically constructing kinetic transition network in polypeptide from top to
      down: trajectory mapping.
AB  - Molecular dynamics (MD) simulation is an important tool for understanding bio
      molecules in microscopic temporal/spatial scales. Besides the demand in improving
      simulation techniques to approach experimental scales, it becomes more and more
      crucial to develop robust methodology for precisely and objectively interpreting
      massive MD simulation data. In our previous work [J Phys Chem B 114, 10266
      (2010)], the trajectory mapping (TM) method was presented to analyze simulation
      trajectories then to construct a kinetic transition network of metastable states.
      In this work, we further present a top-down implementation of TM to
      systematically detect complicate features of conformational space. We first look
      at longer MD trajectory pieces to get a coarse picture of transition network at
      larger time scale, and then we gradually cut the trajectory pieces in shorter for
      more details. A robust clustering algorithm is designed to more effectively
      identify the metastable states and transition events. We applied this TM method
      to detect the hierarchical structure in the conformational space of alanine
      dodeca-peptide from microsecond to nanosecond time scales. The results show a
      downhill folding process of the peptide through multiple pathways. Even in this
      simple system, we found that single common-used order parameter is not sufficient
      either in distinguishing the metastable states or predicting the transition
      kinetics among these states. 

PMID- 25962178
TI  - Psychological resilience after Hurricane Sandy: the influence of individual- and
      community-level factors on mental health after a large-scale natural disaster.
AB  - Several individual-level factors are known to promote psychological resilience in
      the aftermath of disasters. Far less is known about the role of community-level
      factors in shaping postdisaster mental health. The purpose of this study was to
      explore the influence of both individual- and community-level factors on
      resilience after Hurricane Sandy. A representative sample of household residents
      (N = 418) from 293 New York City census tracts that were most heavily affected by
      the storm completed telephone interviews approximately 13-16 months postdisaster.
      Multilevel multivariable models explored the independent and interactive
      contributions of individual- and community-level factors to posttraumatic stress
      and depression symptoms. At the individual-level, having experienced or witnessed
      any lifetime traumatic event was significantly associated with higher depression
      and posttraumatic stress, whereas demographic characteristics (e.g., older age,
      non-Hispanic Black race) and more disaster-related stressors were significantly
      associated with higher posttraumatic stress only. At the community-level, living
      in an area with higher social capital was significantly associated with higher
      posttraumatic stress. Additionally, higher community economic development was
      associated with lower risk of depression only among participants who did not
      experience any disaster-related stressors. These results provide evidence that
      individual- and community-level resources and exposure operate in tandem to shape
      postdisaster resilience. 

PMID- 25962179
TI  - Trait self-control, identified-introjected religiosity and health-related
      feelings in healthy muslims: a structural equation model analysis.
AB  - AIM: The present study attempted to test McCullough and Willoughby's hypothesis
      that self-control mediates the relationships between religiosity and psychosocial
      outcomes. Specifically, this study examined whether trait self-control (TSC)
      mediates the relationship of identified-introjected religiosity with positive and
      negative health-related-feelings (HRF) in healthy Muslims. METHODS: Two hundred
      eleven French-speaking participants (116 females, 95 males; Mage = 28.15, SDage =
      6.90) answered questionnaires. One hundred ninety participants were retained for
      the analyses because they reported to be healthy (105 females, 85 males; Mage =
      27.72, SDage = 6.80). To examine the relationships between religiosity, TSC and
      HRF, two competing mediation models were tested using structural equation model
      analysis: While a starting model used TSC as mediator of the religiosity-HRF
      relationship, an alternative model used religiosity as mediator of the TSC-HRF
      relationship. RESULTS: The findings revealed that TSC mediated the relationship
      between identified religiosity and positive HRF, and that identified religiosity
      mediated the relationship between TSC and positive and negative HRF, thereby
      validating both models. Moreover, the comparison of both models showed that the
      starting model explained 13.211% of the variance (goodness of fit = 1.000),
      whereas the alternative model explained 6.877% of the variance (goodness of fit =
      0.987). CONCLUSION: These results show that the starting model is the most
      effective model to account for the relationships between religiosity, TSC, and
      HRF. Therefore, this study provides initial insights into how religiosity
      influences psychological health through TSC. Important practical implications for
      the religious education are suggested.

PMID- 25962180
TI  - MiR-138 Suppresses Cell Proliferation by Targeting Bag-1 in Gallbladder
      Carcinoma.
AB  - BACKGROUND: MiR-138 is frequently downregulated in different cancer types and is
      thought to be involved in the progression of tumorigenesis. However, the
      molecular mechanism of miR-138 involvement in gallbladder carcinoma still remains
      unknown. METHODS: The expression of miR-138 in 49 gallbladder carcinoma samples
      and paired normal gallbladder samples was analyzed using quantitative reverse
      transcription-polymerase chain reaction. The biological functions of miR-138 and
      Bag-1 (Bcl-2-associated athanogene-1) on cell proliferation were examined using 3
      (4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide and apoptosis assays.
      Targets of miR-138 were predicted using bioinformatics and validated using
      luciferase reporter and Western blot analyses. The in vivo effects of miR-138
      were examined using subcutaneous inoculation of gallbladder carcinoma cells in
      Balb/c nude mice. RESULTS: Compared with their paired normal gallbladder samples,
      the gallbladder carcinoma samples had decreased expression of miR-138 and
      increased expression of Bag-1. Overexpression of miR-138 inhibited the
      proliferation of gallbladder carcinoma cells. Bag-1 was defined as a novel target
      of miR-138. Both the inhibition of Bag-1 by miR-138 and the silencing of Bag-1 by
      siRNA led to alterations of apoptosis-related proteins such as Bcl-2 and Bax.
      Restoring expression of Bag-1 eliminates the effects of miR-138 on cell
      proliferation and apoptosis. Furthermore, overexpression of miR-138 markedly
      inhibited the growth of tumors in the gallbladder carcinoma xenograft model in
      nude mice. CONCLUSIONS: Expression of miR-138 is frequently reduced in
      gallbladder carcinoma when compared to normal cells. Overexpression of miR-138
      inhibited cell proliferation by directly suppressing the expression of Bag-1.
      These results suggest that miR-138 plays an important role in inhibiting the
      growth of gallbladder carcinoma.

PMID- 25962182
TI  - BLOCH equations-based reconstruction of myocardium t1 maps from modified look
      locker inversion recovery sequence.
AB  - Modified Look-Locker Inversion recovery (MOLLI) sequence is increasingly
      performed for myocardial T1 mapping but is known to underestimate T1 values. The
      aim of the study was to quantitatively analyze several sources of errors when T1
      maps are derived using standard post-processing of the sequence and to propose a
      reconstruction approach that takes into account inversion efficacy (eta), T2
      relaxation during balanced steady-state free-precession readouts and B1+
      inhomogeneities. Contributions of the different sources of error were analyzed
      using Bloch equations simulations of MOLLI sequence. Bloch simulations were then
      combined with the acquisition of fast B1+ and T2 maps to derive more accurate T1
      maps. This novel approach was evaluated on phantoms and on five healthy
      volunteers. Simulations show that T2 variations, B1+ heterogeneities and
      inversion efficiency represent major confounders for T1 mapping when MOLLI is
      processed with standard 3-parameters fitting. In vitro data indicate that T1
      values are accurately derived with the simulation approach and in vivo data
      suggest that myocardium T1 are 15% underestimated when processed with the
      standard 3-parameters fitting. At the cost of additional acquisitions, this
      method might be suitable in clinical research protocols for precise tissue
      characterization as it decorrelates T1 and T2 effects on parametric maps provided
      by MOLLI sequence and avoids inaccuracies when B1+ is not homogenous throughout
      the myocardium. 

PMID- 25962181
TI  - Cyclin b1 suppresses colorectal cancer invasion and metastasis by regulating e
      cadherin.
AB  - Cyclin B1, a mitotic cyclin, has been implicated in malignances. However, its
      contribution to colorectal cancer invasion and metastasis are still not well
      understood. Here, we demonstrated that the invasion and metastasis of colorectal
      cancer is regulated by Cyclin B1. Overexpression of Cyclin B1 was observed in
      colorectal cancer tissues, but this elevated expression was negatively associated
      with lymph node metastasis, distant metastasis stage, and TNM stage. The Kaplan
      Meier survival analysis proved that low Cyclin B1 expression was associated with
      poor overall survival of patients with colorectal cancer. Inhibition of Cyclin B1
      in colorectal cancer cells enhanced the cell migration and invasion of three
      different colorectal cancer cell lines. In studying the possible mechanism by
      which Cyclin B1 suppresses colorectal cancer invasion and metastasis, we observed
      that suppression of Cyclin B1 decreased the expression of E-cadherin protein
      level. Our findings suggest that Cyclin B1 could suppress the invasion and
      metastasis of colorectal cancer cells through regulating E-cadherin expression,
      which enables the development of potential intervention strategies for colorectal
      cancer. 

PMID- 25962183
TI  - Assessment of Optic Nerve Impairment in Patients with Neuromyelitis Optica by MR
      Diffusion Tensor Imaging.
AB  - BACKGROUND: Diffusion tensor imaging (DTI) has been used for the evaluation of
      the white matter integrity. In this study, we evaluated optic nerve impairment in
      patients with neuromyelitis optica (NMO) using DTI. METHODOLOGY/PRINCIPAL
      FINDINGS: Optic nerve DTI were performed on 28 NMO patients and 38 normal
      controls. Fractional anisotropy (FA) values were measured in the anterior,
      middle, and posterior parts of the intraorbital optic nerve segment. For the
      posterior intraorbital optic nerve, FA values of BI (0.20+/-0.07), MI (0.24+/
      0.16), and NA (0.25+/-0.14) decreased significantly compared with that of NC
      (0.43+/-0.07) (P<0.05), and ROC analysis demonstrated that the area under the
      curve (AUC) measurements for BI vs. NC, MI vs. NC, NA vs. NC, and NMO (including
      BI, MI, and NA) vs. NC were 0.99, 0.93, 0.88, and 0.96, respectively. The
      corresponding diagnostic sensitivities of ROC analysis were 100%, 80%, 80%, and
      91%; and the specificities were 93%, 97%, 91%, and 93%. CONCLUSIONS/SIGNIFICANCE:
      Decreased FA value in the intraorbital optic nerve, especially in the posterior
      part of the nerve, was demonstrated as a characteristic MR feature for NMO
      related optic nerve impairment.

PMID- 25962185
TI  - [Some trends in chromatography research].

PMID- 25962184
TI  - Mild cognitive impairment: vascular risk factors in community elderly in four
      cities of Hebei Province, China.
AB  - BACKGROUND: Evidence has demonstrated that vascular risk factors (VRFs)
      contribute to mild cognitive impairment (MCI) in the elderly population. Because
      of the race and different diagnosis standard, there is still no definitive
      conclusions. OBJECTIVE: To estimate the VRFs and potential protective factors for
      MCI in elderly population living in the community in North China. METHODS: A
      total of 3136 participants entered the study. They were screened for
      hypertension, coronary heart disease (CHD), and cerebrovascular disease (CVD).
      Cognitive function was assessed with Mini-Mental State Examination (MMSE) and the
      Montreal Cognitive Assessment (MoCA). The diagnosis of MCI was made according to
      Petersen's criteria. We investigated the relationship between vascular risk
      factors, potential protective factors and MCI. RESULTS: A total of 2511 (80%)
      participant belonged to normal group and 625 (20%) participants showed MCI.
      Multiple logistic regression analysis demonstrated that stroke and diabetes, but
      not hypertension or CHD was associated with MCI. Besides, exercise habit could
      lower the risk of MCI. CONCLUSIONS: Vascular Risk Factors, including stroke and
      diabetes, rather than hypertension and CHD are independent risk factors of MCI.
      Involvement in physical activities seems to reduce the risk of MCI.

PMID- 25962186
TI  - [The diagnosis of stupor and coma].

PMID- 25962187
TI  - Gene expression analysis for prostate cancer management.

PMID- 25962188
TI  - Special report: cost-effectiveness studies of new hepatitis C treatments.

PMID- 25962189
TI  - Endovascular treatments for acute ischemic stroke in adults.

PMID- 25962190
TI  - Bronchial thermoplasty for treatment of inadequately controlled severe asthma.

PMID- 25962191
TI  - Special report: medication adherence.

PMID- 25962192
TI  - Special report: early intensive behavioral intervention and other behavioral
      interventions for autism spectrum disorder.

PMID- 25962193
TI  - Non-invasive ventilation: challenges in usage and applications.

PMID- 25962194
TI  - Medical thoracoscopy: a useful diagnostic tool for undiagnosed pleural effusion.
AB  - OBJECTIVE: We aimed to assess the role of medical thoracoscopy in patients with
      undiagnosed pleural effusion. METHODS: Patiens presenting with pleural effusion
      underwent three pleural aspirations. Patients in whom pleural fluid analysis was
      inconclusive underwent closed pleural biopsy for diagnostic confirmation.
      Patients in whom closed pleural biopsy was incolcusive underwent medical
      thoracoscopy using a rigid thoracoscope with a viewing angle of zero degrees was
      done under local anaesthesia and sedation with the patient lying in lateral
      decubitus position with the affected side up. Biopsy specimens from parietal
      pleura were obtained under direct vision and were sent for histopathological
      examination. RESULTS: Of the 128 patients with pleural effusion who were studied,
      pleural fluid examination established the diagnosis in 81 (malignancy 33,
      tuberculosis 33, pyogenic 14 and fungal 1); 47 patients underwent closed pleural
      biopsy and a diagnosis was made in 28 patients (malignancy 24, tuberculosis 4).
      The remaining 19 patients underwent medical thoracoscopy and pleural biopsy and
      the aetiological diagnosis could be confirmed in 13 of the 19 patients (69%)
      (adenocarcinoma 10, poorly differentiated carcinoma 2 and mesothelioma 1).
      CONCLUSION: Medical thoracoscopy is a useful tool for the diagnosis of pleural
      diseases. The procedure is safe with minimal complications.

PMID- 25962195
TI  - Prediction equations for spirometry in adults from northern India.
AB  - BACKGROUND: Most of the Indian studies on prediction equations for spirometry in
      adults are several decades old and may have lost their utility as these were
      carried out with equipment and standardisation protocols that have since changed.
      Their validity is further questionable as the lung health of the population is
      likely to have changed over time. OBJECTIVE: To develop prediction equations for
      spirometry in adults of north Indian origin using the 2005 American Thoracic
      Society/European Respiratory Society (ATS/ERS) recommendations on
      standardisation. METHODS: Normal healthy non-smoker subjects, both males and
      females, aged 18 years and above underwent spirometry using a non-heated Fleisch
      Pneumotach spirometer calibrated daily. The dataset was randomly divided into
      training (70%) and test (30%) sets and the former was used to develop the
      equations. These were validated on the test data set. Prediction equations were
      developed separately for males and females for forced vital capacity (FVC),
      forced expiratory volume in first second (FEV1), FEV1/FVC ratio, and
      instantaneous expiratory flow rates using multiple linear regression procedure
      with different transformations of dependent and/or independent variables to
      achieve the best-fitting models for the data. The equations were compared with
      the previous ones developed in the same population in the 1960s. RESULTS: In all,
      685 (489 males, 196 females) subjects performed spirometry that was technically
      acceptable and repeatable. All the spirometry parameters were significantly
      higher among males except the FEV1/FVC ratio that was significantly higher in
      females. Overall, age had a negative relationship with the spirometry parameters
      while height was positively correlated with each, except for the FEV1/FVC ratio
      that was related only to age. Weight was included in the models for FVC, forced
      expiratory flow (FEF75) and FEV1/FVC ratio in males, but its contribution was
      very small. Standard errors of estimate were provided to enable calculation of
      the lower limits of normal and standardised residuals for these parameters. The
      equations were found to be valid on the test dataset, and therefore, may be
      extended to general population. Comparison with the 1960s equations revealed lack
      of good agreement, and substantially higher predicted FVC with the current
      equations, especially in the forty-years-plus age group, in both males and
      females. Even in the age group upto 40 years, the level of agreement was
      clinically not acceptable. CONCLUSIONS: Validated prediction equations have been
      developed for spirometry variables in adults of north Indian origin using the
      current ATS/ERS spirometry standardisation recommendations. The equations suggest
      an improvement in the lung health of the population over time in the middle-aged
      and the elderly. These equations should address a long-felt unmet need and enable
      a more appropriate evaluation of spirometry data in different chest diseases in
      Indian subjects.

PMID- 25962196
TI  - A study on pulmonary complications of systemic sclerosis in eastern India.
AB  - AIM: This study was undertaken to find out the characteristics of clinical,
      radiological and functional changes affecting the respiratory system in patients
      with systemic sclerosis (SSc) from eastern India, and the association of these
      characteristics with pulmonary hypertension. METHODS: This was a cross-sectional,
      observational study involving 46 patients. Other than the routine tests, anti
      nuclear antibody (ANA), spirometry, diffusing capacity of lung for carbon
      monoxide (DLCO) measurement, chest radiograph, high-resolution computed
      tomography (HRCT) of thorax, 6-minute walk test and echocardiography were done.
      RESULTS: Out of a total of 46 patients, 27 patients had diffuse cutaneous SSc
      (dcSSc) and 19 had limited cuteaneous SSc (lcSSc). Eleven patients had pulmonary
      hypertension. The HRCT revealed diffuse parenchymal lung disease (DPLD) in 32
      (65%) cases. The ANA was positive in 83% cases. Anti-Scl70 was found in 41% of
      patients with dcSSc and anti-centromere antibody was found in 47% of patients
      with lcSSc. Spirometry revealed restrictive pattern in 30 patients; 9 had
      obstruction; and the rest were normal. The DLCO was abnormal in 38 patients. A
      strong correlation was found between reduction in DLCO and pulmonary artery
      systolic pressure (PASP). Also, a strong association was observed between a drop
      of > 4% in oxygen saturation on 6-minute walk test and presence of pulmonary
      arterial hypertension (PAH). CONCLUSIONS: Majority of the patients with SSc had
      restrictive lung disease with abnormal DLCO and features resembling non-specific
      interstitial pneumonia. Nucleolar ANA was predominantly found in patients having
      PAH. Presence of DPLD had a negative association with presence of anti-centromere
      antibody. Reduction in DLCO and a fall of > 4% in oxygen saturation on 6-minute
      walk test may be used as predictors of PAH in asymptomatic individuals.

PMID- 25962197
TI  - Multidrug resistant tuberculosis: trends and control.
AB  - Multidrug resistant tuberculosis (MDR-TB) has been an area of growing concern and
      is posing a threat to the control of tuberculosis (TB). The exact magnitude of
      problem of resistance to anti-tuberculosis drugs worldwide was not known till the
      1994-97 global project on anti-tuberculosis drug resistance surveillance
      initiated by the World Health Organization (WHO) and International Union Against
      Tuberculosis and Lung Diseases (IUATLD). The Global Tuberculosis Report 2014
      estimated that an 3.5% of newly diagnosed and 20.5% of previously treated.TB
      cases had MDR-TB. It has been estimated that 480,000 cases emerged and 210,000
      deaths occurred due to MDR-TB globally in 2013. In India, estimates showed that
      the prevalence of MDR-TB among new and previously treated patients was 2.2% and
      15%, respectively. It is estimated that 99,000 cases of MDR-TB emerge every year
      of which 62,000 were among notified cases of TB in 2013. The MDR-TB is a human
      made problem and results largely from poorly managed cases of TB. Adequate,
      timely diagnosis and optimal treatment of MDR-TB will help curb the epidemic.
      Efforts must be focused on the effective use of anti-tuberculosis drugs in every
      new patient, so as to prevent the emergence of MDR-TB.

PMID- 25962198
TI  - Reversed halo sign.

PMID- 25962199
TI  - Lung cancer presenting with choroidal metastasis in a pregnant woman.
AB  - A 28-year-old, non-smoker pregnant woman who was initially diagnosed to have deep
      vein thrombosis and pulmonary thromboembolism earlier in pregnancy, presented at
      22 weeks of gestation with dyspnoea, visual loss initially in the right eye and
      then in the left eye. Fundoscopic examination revealed metastatic foci,
      suggestive of choroid metastases. Computed tomography of the chest revealed a
      right hilar mass. Fibreoptic bronchoscopy and bronchoscopic biopsy confirmed lung
      adenocarcinoma. As the patient and family wished to continue with the pregnancy,
      chemotherapy with cisplatin and was administered from the 31st week of pregnancy
      and she had undergone Caesarian section in the 32nd week and the baby was
      healthy. We report this case as it is probably the first reported case of lung
      cancer presenting with choroidal metastasis in a pregnant woman.

PMID- 25962200
TI  - B-type natriuretic peptide may be unsuitable for diagnosing central acute
      pulmonary embolism.
AB  - We describe a case of a 90-year-old male admitted to the emergency department
      with deep vein thrombosis and central acute pulmonary embolism. Despite a
      remarkably increased value of D-dimer and a modestly elevated concentration of
      cardiac troponin I, the value of B-type natriuretic peptide was found to be non
      diagnostic. Limited to this single case report, our evidence suggests that the
      measurement of natriuretic peptides is questionable for diagnosing central acute
      pulmonary embolism in the emergency department.

PMID- 25962201
TI  - Metastatic thymic carcinoid: does surgeon have a primary role?
AB  - Thymic carcinoids are rare mediastinal tumours. These are aggressive tumours that
      often present late and have poor prognosis. Primary surgical treatment is
      recommended even in metastatic tumours since the role of adjuvant therapy is not
      well established. We present a case of metastatic thymic carcinoid managed with
      surgical excision.

PMID- 25962202
TI  - Pulmonary capillary haemangiomatosis: a rare cause of pulmonary hypertension.
AB  - Pulmonary capillary haemangiomatosis (PCH) is a rare disorder of unknown
      aetiology, characterised by proliferating capillaries that invade the pulmonary
      interstitium, alveolar septae and the pulmonary vasculature. It is often mis
      diagnosed as primary pulmonary hypertension and pulmonary veno-occlusive disease.
      Pulmonary capillary haemangiomatosis is a locally aggressive benign vascular
      neoplasm of the lung. We report the case of a 19-year-old female who was referred
      to us in the early post-partum period with severe pulmonary artery hypertension,
      which was diagnosed as PCH by open lung biopsy.

PMID- 25962203
TI  - Electronic cigarettes: facts and myths.
AB  - E-cigarettes are devices designed to deliver nicotine to users without burning
      tobacco. These are being marketed globally as a healthier substitute to the
      conventional cigarettes and as smoking quitting aids. The use of these devices
      has increased recently in developed countries with approximately 1.3 million
      users reported in the United Kingdom in 2013. Perception of these products as a
      safe alternative, appealing advertisements, and lax regulatory policies have
      helped gain popularity among the public. Despite all these claims, a debate is on
      going because of insufficient scientific data regarding safety and efficacy of e
      cigarettes as well as awareness of the potential health hazards. To solve the
      dilemma, more scientific studies in this field are required. Prompt regulatory
      response with strict vigilance on marketing and advertising may be desirable in
      the interest of users and public at large.

PMID- 25962204
TI  - The urgent need to prevent type 1 autoimmune childhood diabetes.
AB  - Clinical onset of autoimmune Type 1 diabetes mellitus (T1DM) develops after an
      asymptomatic, complex interaction between host genetic and environmental factors
      lasting several years. The world-wide increase in T1DM incidence with no cure in
      sight necessitates the identification of the causative environmental factors in
      order to develop methods for preventing them from participating in the autoimmune
      process leading to T1DM. Human trials to prevent insulitis or development of T1DM
      (secondary prevention trials) have not as yet produced satisfactory outcomes
      despite promising results from T1DM animal models, possibly because the
      autoimmune response had already progressed too far and could not be stopped or
      reversed. Primary prevention trials conducted with individuals with increased
      genetic risk, but without signs of autoimmune response or metabolic abnormalities
      have also not yet produced any clear benefit. A correlation between month of
      birth and T1DM implicated seasonal infectious pathogens in the etiology of T1DM.
      This has prompted a search for those seasonal pathogens including viruses that
      might lead to onset of T1DM. Many studies investigated immediate viral triggers,
      e.g., viral infections at the time of clinical onset of T1DM. Fewer studies have
      investigated virus infections as the initial or early trigger in a cascade of
      events leading to development of TIDM. Seasonal virus infections of pregnant
      women may be transmitted in utero and induce the first damage to the developing
      fetus's beta-cells. The identification of specific pathogenic viruses may enable
      development for pregestational vaccines to diminish the incidence of childhood
      T1DM.

PMID- 25962205
TI  - Cortisol levels in central adrenal insufficiency: light and shade.
AB  - Evaluating children or adolescents with central adrenal insufficiency (CAI) is a
      difficult task in clinical practice, especially in subjects with hypothalamic
      pituitary diseases and partial ACTH deficiency, or in those with recent pituitary
      surgery or brain irradiation when the adrenal cortex may still be responsive to
      stress. In 2008, a meta-analysis reported a three-step approach for evaluating
      patients at risk for CAI with no acute illness. In particular, the authors
      recommended the evaluation of morning cortisol, a low dose ACTH test (LDST) and
      the "gold standard" insulin tolerance test or metyrapone test if the low LDCT was
      not diagnostic. Cortisol and ACTH secretion exhibit significant fluctuation
      throughout the day. The reference ranges supplied by labs are so wide that they
      only flag up extremely low cortisol levels. Interpreting the results correctly
      can be difficult for a physician without an experience in adrenal dysfunctions.
      The lack of uniformity in these cut-off levels could in part be attributed to
      differences in study populations, variability of dynainic tests, the use of
      different serum cortisol assays and dissimilar cut-off peak serum cortisol
      response indicative of a normal axis response and the difference in the clinical
      context in which the studies were done. Therefore, Laboratories have to advertise
      the need to establish reference values for given populations, both for basal or
      stimulated hormone levels. Failure to apply this rule may elicit false-positive
      and more critically, false-negative results. LDST (1 pg synthetic ACTH as iv
      bolus with measurement of serum cortisol) has been proposed as a sensitive test
      for the diagnosis of CAl. However, the advantage of LDST compared with the high
      dose test may be offset by the technical difficulties inherent to dilution of 250
      pg ampoules. Clinical judgment remains imperative especially regarding the use of
      glucocorticoid supplementation during extreme stress.

PMID- 25962206
TI  - Anti-PIT-1 antibody syndrome; a novel clinical entity leading to hypopituitarism.
AB  - Various hypothalamic-pituitary diseases cause hypopituitarism. Inflammation
      related to autoimmunity also causes hypopituitarism. Hypophysitis is a
      representative disease caused by autoimmunity. Generally, anterior pituitary
      hormones are non-specifically impaired in this condition, but specific hormone
      defects have been reported in some cases. Anti-PIT-1 (pituitary-specific
      transcription factor 1) antibody syndrome is a novel clinical entity that
      presents an acquired combined pituitary hormone deficiency characterized by a
      specific defect in growth hormone, prolactin, and thyroid-stimulating hormone.
      Circulating anti-PIT-1 antibody along with various autoantibodies are detected
      with multiple endocrine organopathy, meeting the definition of autoimmune
      polyglandular syndrome. Mechanistically, cytotoxic T lymphocytes that
      specifically react with PIT-1 protein play an important role in the development
      of this syndrome.

PMID- 25962207
TI  - Obesity management in Prader-Willi syndrome.
AB  - Prader-Willi Syndrome (PWS) is one of the most common genetic causes of obesity.
      The phenotype of obesity in PWS is unique and characterized by hyperphagia,
      earlier meal initiation, delayed meal termination, reduced energy expenditure,
      abnormal gut hormone profiles, as well as irregular responses to food in areas of
      the brain associated with satiety and reward. Management of obesity is necessary
      to avoid major morbidity. The relentless food-seeking behavior associated with
      PWS such as stealing, hoarding food, eating inedibles, and lying about eating,
      can cause turmoil both inside and outside of the home. Management is challenging
      for both patients and caretakers, but at this time there are limited medical
      therapies available besides dietary restriction and behavior management. However,
      current research shows promise for discovery of additional treatment options for
      hyperphagia and obesity management in PWS.

PMID- 25962208
TI  - Propranolol induced hypoglycemia.
AB  - ince 2008, propranolol has become the first line therapy for infantile
      hemangiomas. Due to the fact that infantile hemangiomas are the most common
      vascular tumors of infancy, the use of systemic propranolol has been dramatically
      increased in the last few years. The reported adverse effects of propranolol in
      the treatment of infantile hemangiomas included symptomatic hypoglycemia. In this
      review we will summarize those reports and will offer guidelines for prevention
      of hypoglycemia secondary to propranolol therapy.

PMID- 25962209
TI  - The 48th Annual Scientific Meeting of the Japanese Society for Pediatric
      Endocrinology (JSPE), Hamamatsu (Shizuoka), Japan (September 25-27, 2014).

PMID- 25962210
TI  - Selected highlights of the VIII International Symposium of Clinicians for
      Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) on Growth,
      Puberty and Endocrine Complications in Thalassaemia. Auditorium of the Sultan
      Qaboos University (SQU) Muscat (Sultanate of Oman), 20th of December 2014.
AB  - The VIII ICET-A International Symposium was held in Muscat (Sultanate of Oman) on
      the 20th of December, 2014. The symposium included four sessions on a wide range
      of topics covering growth disorders and endocrine complications in thalassaemia.
      Despite the fact that endocrine complications are very common in multi-transfused
      thalassaemia patients a recent survey conducted by the International Network of
      Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A)
      in 2014 in Acitrezza (Catania, Italy) showed that the major difficulties reported
      by hematologists or pediatricians experienced in thalassaemias or thalassaemia
      syndromes in following endocrine complications included: Lack of familiarity with
      medical treatment of endocrine complications, interpretation of endocrine tests,
      lack of collaboration and on-time consultation between thalassaemic centres
      supervised by haematologists and endocrinologists. Endocrine monitoring of
      growth, pubertal development, reproductive ability and endocrine function in
      general are essential to achieve a good quality of life as well as controlling
      the pain which results from the defects of bone structure, all of which increase
      with the age of patients. Such comprehensive care is best provided by
      coordinated, multidisciplinary teams working in expert centres. The
      multidisciplinary team must include an endocrinologist, preferably someone
      experienced in the management of hormonal deficiencies caused early in life by
      transfusion-induced iron overload.

PMID- 25962211
TI  - "Proceedings of the 22nd Aschauer Soiree on Growth and Health Screening", held at
      Altenhof, Germany, November 15th, 2014.
AB  - Twenty-five scientists met at Aschauhof, Altenhof, Germany, to discuss various
      aspects of the complex network of modern health screening, focusing on current
      scientific topics including medical sciences, human biology, and mathematics; on
      problems in implementing these results at the practical level of physicians,
      nurses, technicians, and engineers; and the level of administrative and political
      decisions. Whereas major scientific advancements have been published in the
      understanding and the bio-statistical evaluation of anthropometric screening
      parameters such as serial measurements of height and weight for preventive
      medical check-ups, BMI screening and surveillance in schools, etc., the
      implementation of these advancements into current health screening concepts,
      strategies and decision-making is poor. Fear of discrimination, misperception of
      body image, behavioural responses and political concerns, meanwhile dominate and
      negatively interfere with the implementation of recent scientific results into
      public health screening concepts and practices.

PMID- 25962212
TI  - [The Helvetius dynasty].
AB  - The Helvetius dynasty originates from the Principality of Anhalt, in Germany.
      George Vigelius, one of its ancestors, was born in the Palatinate (Germany) and
      studied theology in the town of Basel (Switzerland), after which he was given the
      surname Swietser. In 1649, his eldest son, Johann Friedrich Swietser, moved to
      the United Provinces and changed his name into Johan Frederik Helvetius. In 1656,
      he took his doctorate of medicine at the university of Harderwyck Guelderland).
      He settled in Amsterdam and moved later to The Hague, where he had a lightning
      career. Three of his four sons studied medicine in Leyden: Jean-Balthasar,
      Philippe-Maximilien, and Joseph-Jean. Jean-Adrien, the second son of Johann
      Friedrich, settled in Paris and took his doctorate of medicine at the university
      of Reims, using the pseudonym of Christian-Lebrecht Helvetius. He had a
      prosperous career. He was the father of Jean-Claude-Adrien Helvetius, who became
      also a successful physician and first physician to the queen of France. His
      grandson was Claude-Adrien Helvetius, who became a leading philosopher and
      writer.

PMID- 25962213
TI  - [Public health in the mountain zone in the nineteenth century. The records of
      births and deaths in the village of Beost, Ossau valley, Bearn].
AB  - We report a study on 809 births and 885 deaths collected from the civil
      registries of the Pyrenean village of Beost, Ossau Valley, Bearn, France, during
      the entire 19th century. Among the studied parameters, some give us interesting
      data on the population history. Thus, the rate of mortality under 1 year of age
      (110,7 per thousand), the global longevity of this population (mean age at death:
      45,8 years) and the absence of significant increase in mortality during the
      winter months and periods of difficulty for food availability argue in favor of a
      quite satisfactory sanitary level. Nevertheless, the reduced longevity of
      illegitimate children (nine deaths often before the age of 7) suggests an absence
      of care for this population category who was socially rejected. Furthermore, the
      proportion of women dying between 21 and 40 years of age was twice than that of
      men, which could be explained by maternity-related medical complications. The
      seasonality of births (and therefore of conceptions) is less typical than in the
      other mountain populations. Finally, we may note an increased mortality at the
      end of 1856 due to a cholera epidemic and in 1870 because of small pox.

PMID- 25962214
TI  - [History of cancer and chemotherapy before chemotherapy].
AB  - Chemotherapy stands today for cancer. In 1909, Paul Ehrlich (1854-1915) advocates
      the use of arsphenamine by infusion. So, he is considered as the father of
      chemotherapy. In fact, the first to have thought through chemotherapy was Sir
      Christopher Wren (1632-1723). In 1676, ideas and experiments on animals had
      sufficiently progressed to allow Michel Ettmuller (1644-1683) to publish the
      first edition of his book and several others were printed until 1753. In this
      book, he describes the first intravenous treatment, it sets the first
      indications, dosages and different products which can be used. However this
      method has been forgotten until the late 19th century.

PMID- 25962215
TI  - [Fight against epidemics: Austrian prisoners in Troyes].
AB  - The victories near Ulm and Elchingen, where the Napoleonic army took 60000
      prisoners between 15th and 20th of October 1805, lead to the arrival at Troyes
      (county "Aube") of nearly 2000 Austrian soldiers to be held inside former
      monasteries among whose, mainly the Jacobinians casern where more than half of
      them stayed. At the beginning of 1806, the government sent the epidemics medical
      practitioner Dr Desgenettes on an inspection tour to control the state of health
      of the populations of places where foreign prisoners were held, which lead him
      through several counties of the North-eastern part of France, where he surveyed
      several diseases ranging from all kinds offevers up to dysentery, scabies or
      gangrenes. With the means of acid fumigations invented by the chemist Guyton
      Morveau from Dijon, the authorities took care of combating and preventing the
      epidemics in the caserns. As soon as October 1805, the epidemics medical
      practitioner Dr Pigeotte from Troyes wrote to the county governor his
      observations recommending a better diet, airing of the rooms and also calls to
      take some exercise. All these precepts showed an astonishing modernity.

PMID- 25962216
TI  - [The fate of the wood of the Fabrica of 1543].
AB  - Destiny of the wood blocks which have been used for engraving of illustrations of
      1543 edition of the Fabrica is really outstanding. Several times lost and found
      again, they were transported over Europe in a surprising conservation state, for
      more than four centuries. Made by the famous Venitian wood-cutters, the blocks
      cross the Alps to join up Basel in Switzerland and Joannes Oporinus, the printer.
      Felix Platter uses 48 Vesalian wood-blocks for his own treaty in 1583. These
      blocks reappear in Augsburg in 1706, at the printer Andreas Maschenbauer's; they
      are found again by Von Wollter from Ingolstadt: they are used to illustrate
      Leveling's anatomy book in 1781 and 1783. Ingolstadt university and the blocks
      will be transferred to Landshut because of Napoleon's war, then to Munich in
      1826. But in 1892 147 blocks are found again in the library; and are forgotten
      again. Forty years after, 230 blocks are discovered again! Icones anatomicae
      represent the last and fabulous edition made in 1934. The Second World War closes
      this epic with the library fire on July 13th 1944: none of these precious blocks
      remains today.

PMID- 25962217
TI  - [The copy of De humani corporis fabrica of Andreas Vesalius of the municipal
      library of Reims].
AB  - The author presents a copy of the De humani corporis fabrica by Andreas Vesalius;
      this book is preserved in the department of rare books of the municipal Library
      in Reims. This copy is a first edition as the author gives positive proofs. This
      book results of a donation to the Minimes's congregation of Reims by Seigneur
      Guillaume Le Vergeur, Count of Saint Souplet and Baillif of Vermandois in the
      17th century. Guillaume Le Vergeur has also given other precious books to the
      monastery's library and his name is inscribed on the register of obituaries and
      on the pediment of the Minimes' Church.

PMID- 25962218
TI  - [The reception of Vesalius in Spain and England].
AB  - This paper discusses the depiction of engravings taken from Vesalius's, Valverde
      de Hamusco's and Casserio 's treatises in portraits during the 16th and the 17th
      centuries to understand better the reception of the Fabrica in Spain and England.

PMID- 25962219
TI  - [From Vesalius to Descartes: the heart, the life].
AB  - At the end of 1629, Descartes, settled in the Lower Countries, began studying
      anatomy and performing dissections in order to write L'Homme (The Treatise on
      Man). He acknowledged his debt towards "Vezalius and the others". In those years,
      in Europe, the influence of Vesalius was increasing, as shown by Rembrandt's
      Anatomy of Dr Tulp and by the Theatrum anatomicum by Caspar Bauhin. Descartes
      rejected the divisions of the soul, then a common place in medical treatises, and
      he stated a principle of life defined by the heath in the heart linked to the new
      demonstration of the circulation of the blood by William Harvey.

PMID- 25962220
TI  - [Vesalius and the flat of Daremberg].
AB  - Who was Charles Daremberg? Why and how did he become interested in Vesalius? Why
      was he unable to really understand his work? Why did he tone down the general
      tune of praise?

PMID- 25962221
TI  - [From ergot of rye to Mediator].

PMID- 25962222
TI  - [Saving osteoporosis!].

PMID- 25962223
TI  - [Thirty years of bone disease in Geneva].
AB  - During thirty years of bone pathologies in Geneva, one has assisted to and
      sometimes a little bit contributed to major advances in the management of
      patients with bone diseases.

PMID- 25962224
TI  - [Bone health in Geneva retirees].
AB  - GERICO (Geneva Retirees Cohort) is a cohort of 953 men and women recruited at the
      age of 65 in Canton of Geneva, Switzerland, providing a picture of bone health at
      retirement time. Despite few comorbidities and good nutritional intake and
      vitamin D status, 30% of subjects have a history of vertebral or clinical
      fracture after the age of 45, 20% of women and 11% of men have osteoporosis
      assessed by DXA. 22% have a 10-year probability of a major osteoporotic fracture
      assessed by FRAX greater than 15%, -i.e. the current intervention thresholds
      recommended in this age-class in Switzerland. Nevertheless, only 1.4% subject
      benefits of an anti-osteoporotic drug. These data underscore the importance of
      primary and secondary prevention of osteoporosis and fractures in healthy elderly
      at time of retirement.

PMID- 25962225
TI  - [DXA imaging: the multifunction Swiss army knife?].
AB  - The significant progress on the quality and resolution of the images obtained by
      "Dual X-ray Absorptiometry" or DXA has permitted on one hand to improve some
      existing features and on the other to develop new ones, significantly refining
      the care of our patients in various pathologies. For example, by improving the
      prediction of fracture risk by indirect analysis of micro- and macro-architecture
      of the bone, by looking for markers of associated bone diseases (research
      vertebral fractures or atypical femoral fractures), or by assessing the metabolic
      status by the measurement of body composition. With the best performing DXA
      devices we will soon be able, in clinical routine, to determine bone age, to
      estimate cardiovascular risk (by measuring the calcification of the abdominal
      aorta) or to predict the progression of joint osteoarthritis and its evolution
      after surgical management.

PMID- 25962226
TI  - [Definition of sarcopenia and diagnostic evaluation in clinical practice].
AB  - Aging is associated with progressive increase in body fat and a corresponding
      decline in lean muscle mass. When the decrease in muscle mass reaches a critical
      threshold, this may affect muscle strength and consequently limit the ability to
      cope with the activities of daily living, reducing the independence of elders. It
      is widely accepted to define sarcopenia as the loss of skeletal muscle mass and
      strength that occurs with advancing age. It is more difficult to establish cut
      off points which are clinically relevant. The purpose of this paper is to
      summarize the definitions of sarcopenia and the assessment tools that can be used
      in clinical practice.

PMID- 25962227
TI  - [News in osteogenesis imperfecta: from research to clinical management].
AB  - Osteogenesis imperfecta (OI) is a rare genetic disease. Today we are able to
      propose an adapted and efficient management to the patients with this rare
      disorder (and their families) thanks to a strong collaboration of clinicians and
      researchers. Recent knowledge regarding the genetics of OI permits an accurate
      diagnosis of the specific type of OI and its own molecular mechanism, a genetic
      counseling for family planning and prenatal diagnosis, and in addition more
      targeted therapeutic options. A specific support with re-education for patients
      with OI is necessary and efficient. To optimize patient care, a multidisciplinary
      consultation is proposed at the CHUV, moreover a web site is available for
      patients, families and therapists: www.infomaladiesrares.ch

PMID- 25962228
TI  - [Improvement of fracture healing with teriparatide: series of 22 cases and review
      of the literature].
AB  - Pseudoarthrosis is defined as a non healing fracture 9 months after trauma and
      without radiological progression within the last three months. Osteoporotic
      fractures have a greater risk of chirurgical complications. The question of
      giving a medical treatment in the purpose of accelerating fracture healing is an
      increasing concern. There are data showing that with teriparatide (bone anabolic
      treatment derived from the parathyroid hormone) bone healing and functional
      status are improved, with or without surgery, in the case of either typical or
      atypical fractures. The risks of this treatment are low but health insurance
      agreement is needed in this indication. We report our experience with the use of
      this molecule, out of the official indication, in complex situations of non
      healing fractures.

PMID- 25962229
TI  - [Calcinosis cutis associated with connective tissue diseases].
AB  - Calcinosis cutis is characterized by calcified deposits in the skin and in
      subcutaneous tissues. The potential complications are ulceration, infection,
      functional limitation. According to serum calcium/phosphate levels, calcinosis
      cutis is classified in 4 subtypes: dystrophic, metastatic, iatrogenic,
      idiopathic. In dystrophic calcinosis, calcium/phosphate serum levels are within
      range. Dystrophic calcinosis occurs in damaged tissues and is associated with
      several connective tissue diseases (mainly systemic sclerosis and
      dermatopolymyositis). Its physiopathology remains unclear. Despite different
      therapeutic modalities in the litterature, there is no standard therapy for
      calcinosis. Thus, larger controlled studies are necessary.

PMID- 25962230
TI  - [Management of patients with dementia living at home].
AB  - Caring for a patient with dementia who lives at home, sometimes alone, presents a
      constant challenge for general practitioners. This article uses a clinical
      vignette to explore the initiation of medical care and treatment in an elderly
      patient with dementia. We specifically address how to inform the patient and
      family of the initial diagnosis and important issues to discuss from the start.
      We also examine issues such as delirium, medication adjustments, behavioral
      difficulties, feeding, and treatment of associated pathologies such as
      hypertension and diabetes.

PMID- 25962231
TI  - [Smoking: is the electronic cigarette a nicotine substitute?].

PMID- 25962232
TI  - [Autonomy and responsibility with respect to International Women's Day].

PMID- 25962233
TI  - [In France, "deep and terminal sedation" becomes a national matter].

PMID- 25962234
TI  - [Go to the sauna and live longer].

PMID- 25962235
TI  - [2015: to be or not to be "noninvasive" screening for trisomy 21? (2)].

PMID- 25962236
TI  - [Thousands in Swiss borders could return to the LAMal].

PMID- 25962237
TI  - [Mr. Price wants a federal law regulating hospital rates].

PMID- 25962238
TI  - [Pleasure and pain: an ongoing conflict?].

PMID- 25962239
TI  - [The digital doctor].

PMID- 25962240
TI  - [The Arrow project--excellence in medical education in Sheba Medical Center].

PMID- 25962241
TI  - [Use of fecal microbial transplantations for disease states in Israel].
AB  - The enteric microbial population (microbiota) has a tremendous impact on our
      health and multiple disease states are associated with an alteration of the
      enteric microbial profile. It has been suggested that fecal microbial
      transplantation (FMT)--a transfer of fecal microbiota from a healthy donor to a
      sick person, may be beneficial for the treatment of certain diseases such as
      obesity, diabetes and inflammatory bowel diseases. Currently, this treatment has
      been approved in Israel, as well as in other countries, for the treatment of
      recurrent Clostridium difficile infection (RCDI). The establishment of a stool
      bank from healthy donors makes this therapy available and easy to use. The
      rationale for using FMT for RCDI, and the methods for its performance and for
      choosing patients and donors, along with the open questions and the future for
      this therapy, are presented in the current editorial.

PMID- 25962242
TI  - [Reconstruction in plastic surgery using osmotic tissue expanders].
AB  - BACKGROUND: Tissue expander is a major reconstructive modality. Its main
      disadvantages include: long and inconvenient period of inflation with temporary
      deformity of the surrounding tissue. Osmotic expander was developed in order to
      eliminate some of these limitations. It is a self-filling device which absorbs
      fluids in order to achieve tissue expansion faster. PURPOSE: We present our
      experience with 28 consecutive cases of tissue reconstruction using osmotic
      expanders. We wish to emphasize the main advantages and limitations of this
      device. METHODS: The present study was launched in May 2008, until April 2014,
      for twenty eight patients, median age 26 years with reconstructions using an
      osmotic expander (total of 35 expanders). The reasons for using tissue expander
      included large congenital nevi (75%) and scars. RESULTS: In all of the cases, the
      operative and post-operative management was uneventful. During the expansion
      period, there were 2 outpatient clinical visits. The average expansion time was 9
      weeks. In 11% (three patients) there was partial extrusion of the expander. In
      all other cases there were no complications and the final aesthetic results were
      satisfying. DISCUSSION: Osmotic expander is an advanced modality for tissue
      reconstruction. The final shape and size are precisely predictable. Its initial
      small size allows for a small surgical incision and short overall operating time.
      The expansion period is shorter and more convenient for the patient. Its main
      disadvantage includes the inability to control the filling rate and the need to
      remove the expander in case of damage to the overlying tissue. CONCLUSION:
      Osmotic expander is a reliable tool for tissue expansion. It allows for a
      satisfying aesthetic result in a shorter period of time and with less
      inconvenience to the patient.

PMID- 25962243
TI  - [Delivery during time of shift change is not a risk factor for obstetric
      complication: a historical cohort study].
AB  - BACKGROUND: The time of shift change is a unique time because the continuity of
      routine care is interrupted. The association between delivery during time of
      shift change and obstetric complications has not been evaluated. OBJECTIVE: We
      hypothesized that delivery during time of shift change is at risk for obstetric
      complications. METHODS: A historical cohort study was performed of all women with
      a singleton pregnancy undergoing a trial of labor at term during 2006-2010. Data
      was extracted from a computerized database that is continuously updated during
      Labor. The hour of delivery was divided into two categories: "morning shift"
      (09:30-15:00) and "time of shift change" which was defined 30 minutes prior to
      and 90 minutes past the official time of shift change, which occurs twice daily
      at 07:30 and 15:30. Multivariate logistic regression models were implemented to
      estimate the association between deliveries during "time of shift change"
      compared to "morning weekdays", with instrumental delivery (primary outcome) and
      prolonged second stage, unplanned cesarean section, postpartum hemorrhage, 5
      minutes Apgar score < 7, admission to neonatal intensive care unit (NICU) and
      prolonged maternal hospitalization (secondary outcome). RESULTS: A total of
      16,341 deliveries were included in the cohort. No statistical difference in
      instrumental vaginal delivery was documented for women delivering during "time of
      shift change compared to morning shift weekdays (OR = 0.96, 95% CI: 0.83- 1.11, p
      = 0.605). None of the secondary outcomes were found at risk for women delivering
      during "time of shift change". CONCLUSIONS: Delivery during "time of shift
      change" does not pose additional risk for obstetric complications.

PMID- 25962244
TI  - [The effect of fever on blood oxygen saturation in children].
AB  - INTRODUCTION: Blood temperature is inversely correlated with oxygen-hemoglobin
      affinity as demonstrated by in-vitro oxyhemoglobin dissociation curve (ODC)
      experimentation. OBJECTIVE: To evaluate the real-life effect of fever on blood
      oxygen saturation (SO2) in children. METHODS: Children treated in the Pediatric
      Emergency Department at the "Shaare Zedek" Medical Center with a body temperature
      > 38.50C were included in the study. Children suffering from active lung disease
      were excluded. The following parameters were collected before and 90 minutes
      after administering antipyretic therapy: temperature, SO2, respiratory rate and
      pulse rate. RESULTS: Twenty-two subjects completed the study. The mean decrease
      in temperature was 2.030C. Following the decrease in body temperature, a rise in
      SO2 was noted in 17 subjects (77.3%). The mean SO2 before the antipyretic therapy
      was 96.18%. The mean SO2 after the drug administration was 97.73%. The average
      rise in SO2 was 1.55 +/- 1.79% (p = 0.001). CONCLUSIONS: Fever in children is
      associated with decreased SO2. This decrease is not clinically significant in
      patients with normal baseline SO2. Calculation reveals that in patients with
      baseline SO2 close to the steep region of the ODC, the same increase of body
      temperature will cause a significantly greater decrease in SO2. In patients with
      a baseline SO2 of 91% at body temperature of 370C, an increase in body
      temperature to 400C is anticipated to cause a 5% decrease in SO2. This decrease
      has major potential implications concerning treatment decisions.

PMID- 25962245
TI  - [Effect of a computer application on appropriate use and control of broad
      spectrum antibiotics].
AB  - BACKGROUND: Antibiotics are among the greatest contributions of modern medicine.
      However, since the onset of the antibiotic age, resistance has emerged,
      threatening the future usability of these drugs. The complexity of antibiotic
      prescribing and associated expense has led to the development of infectious
      disease (ID) expert stewardship programs. PURPOSE: To describe an in-house
      created computer application, in use since 2005 with which all restricted
      antimicrobials are ordered and approved by ID physicians before being supplied by
      the pharmacy. RESULTS: In the nine years since the application was adopted by the
      entire hospital, 173,436 prescriptions for restricted antibiotics have been
      ordered through the application, of which 52% were for male patients, 8% for
      children <= 20 years, 31% for adults 21-70 years old and 61% for patients > 70.
      All prescriptions were reviewed by ID physicians; their response included
      approval (mean 87%, range 82-92%), rejection (7%, 3-12%), or change (6%, 4-18%).
      The latter two decisions always involved written and/or oral interaction with the
      prescribing physicians. The result analysis showed that: by clinical diagnoses,
      the approval rate ranged from 82% (for central line associated infection) to 94%
      (for tuberculosis); by class of antimicrobial, the approval rate ranged from 71%
      (IV ciprofloxacin) to 95% (IV amoxicillin-calvulanate). Overall hospital
      expenditure on antimicrobials, corrected by 100 admissions and 100 admission
      days, did not change significantly. CONCLUSIONS: During the nine years of its
      use, the described computer program has significantly contributed to physician
      awareness of appropriate antibiotic use, provided tools to assist physicians in
      their choice of antimicrobial treatment, allowed ID supervision with
      unprecedented scope and depth and has significantly contributed to cost control.

PMID- 25962246
TI  - [Bile lake post Kasai hepatoportoenterostomy in biliary atresia].
AB  - In this case report we describe a boy with extrahepatic biliary atresia who
      underwent a Kasai hepatoportoenterostomy at six weeks of age. Beginning several
      weeks post-op, he had recurrent cholangitis inadequately controlled by various
      antibiotic prophylaxis regimens. Imaging revealed the development of several bile
      lakes in the liver hilum. Due to the recurrent nature of his cholangitis, and
      some evidence of acutely impaired biliary drainage, he underwent a refashioning
      of his portoenterostomy with resultant improved drainage. However, shortly
      thereafter, the patient developed ongoing fever and anemia. Culture of the bile
      lake aspirate grew multiresistant Klebsiella and a 6 week course of parenteral
      meropenume controlled his fever and his anemia improved. Following treatment
      cessation his fever and anemia returned. A biliary drain was inserted into his
      larger bile lake and following another course of parenteral antibiotics he has
      remained free of clinically detected cholangitis despite ongoing contamination of
      drained bile fluid. The development of bile lakes after Kasai
      hepatoportoenterostomy is not an uncommon finding. This have been associated with
      worse prognosis including increased incidence of cholangitis. Often, conservative
      treatment with prophylactic antibiotics suffices, however, in rare cases, more
      aggressive intervention may be considered including percutaneous bile drainage or
      surgical management. The benefit of these management strategies must be balanced
      with the potential gain regarding quality of life and delaying transplant, on an
      individual basis.

PMID- 25962247
TI  - [Foreign body aspiration in children].
AB  - Foreign body (FB) aspiration occurs mainly in children under 3 years of age and
      is one of the most frequent causes of accidental death under 12 months of age.
      The increased risk of FB aspiration in children is due to the different structure
      of the pharynx and the upper airways compared to adults. In addition, children
      have an immature swallowing mechanism and they most commonly aspirate food
      stuffs. FB aspiration is usually a sudden and dramatic event when the child feels
      that he is suffocating or choking. After the acute event, the clinical
      presentation widely ranges from severe respiratory distress to the most minimal
      symptoms. Bronchoscopy is the best diagnostic and therapeutic modality for FB
      inhalation. Prevention and rapid diagnosis can be lifesaving. In 2010, the
      American Academy of Pediatrics published a position paper on prevention of FB
      aspiration. The association calls for more proactive preventative measures to
      protect children from FB aspiration and to prevent mortality and morbidity. These
      include: 1. Raising awareness of parents and caregivers to supervise children and
      create a safe environment for them. 2. Promoting legislation and enforcing
      regulations that will prevent dangerous products being sold for children. 3.
      Changing the design of products, especially food products and toys, that will
      reduce the risks of choking. In this overview we will show the principles of
      diagnosis of FB aspiration and a flow chart including when flexible or rigid
      bronchoscopy is required.

PMID- 25962248
TI  - [The reproductive system in Prader-Willi syndrome].
AB  - Prader-Willi syndrome (PWS) is a genetic syndrome caused by the lack of
      expression of imprinted genes located on paternal chromosome 15q11-q13,
      characterized by endocrine defects, an insatiable appetite, short stature,
      cognitive and behavioral difficulties and dysmorphic features. Nearly all PWS
      males and most PWS women show clinical and/or laboratory evidence of
      hypogonadism, affecting their habitus, health and quality of life. Until
      recently, hypogonadism in PWS was generally considered to be of centrall,
      hypothalamic origin. However, recent studies have shown that primary gonadal
      dysfunction is the major contributor to hypogonadism in this condition, while
      severe gonadotropin deficiency is rare. Despite clinical and laboratory evidence
      of hypogonadism, young adult PWS men and women have sexual and romantic interests
      and aspirations. Pregnancies have been reported in a few women with genetically
      documented PWS. Fertility has not been reported in PWS men. Recognition of these
      interests is essential for physicians and caregivers in order to offer proper
      anticipatory guidance, psychological and sex education and counseling. Individual
      variations in pubertal development, reproductive hormone profiles, bone-mineral
      density and individual appeal need to be considered when recommending sex hormone
      replacement in this population. Testosterone should be considered in most
      hypogonadal PWS males, considering possible side effects. Hormone replacement may
      be indicated in PWS women with decreasing bone mineral density or in PWS women
      who wish to have regular menses. Contraception should be considered in women with
      normal inhibin B levels. Hormone replacement is likely to improve bone density,
      quality of life and body image.

PMID- 25962249
TI  - [Phyto-adaptogens--protection against stress?].
AB  - The term adaptogen was invented in the former USSR. An adaptogen increases body
      resistance to physically, chemically or biologically noxious factors, thereby
      having a normalizing effect on body functions and inflicting no harm. Most of the
      research took place in the USSR and in Scandinavian countries and was not
      published in English. In the last decades, some research has been performed in
      Western Europe and in the USA and was also published in English. From the
      research it is possible to learn about the efficacy of the adaptogen use as a
      single dose and on long term use and the differences between the various
      adaptogens. In this article there is a review of the studies and explanations of
      the adaptogenic activity. Adaptogenic effects on different functions in humans
      and animals are mentioned

PMID- 25962250
TI  - [Do's and don'ts in the establishment of an integrative medicine service in the
      public health care system--challenges and insights].
AB  - Although gratifying, it is somewhat misleading to describe the progress made in
      recent years in the field of integrative medicine just by counting the number of
      new programs established. This count, albeit ever-increasing, represents only one
      facet of the complex challenge that should concern us all--the development of a
      better healthcare system. In the real field, other rules apply. It is not
      sufficient for new integrative medicine services to survive or even to thrive if
      this is done in parallel to, or worse off in disconnect from, conventional
      medicine. The two systems, complementary and alternative medicine (CAM) and
      allopathic medicine, must collaborate in harmony for the sake of synergy. In
      order for that to happen, careful prior planning that addresses the multiple
      interests of the various stakeholders is warranted. This paper describes five key
      challenges and insights [institutional acceptance, Leadership support, the day
      after, the human factor, and program evaluation) gained from establishing an
      integrative oncology section within a tertiary academic medical center in Israel.
      It includes practical advice and useful tips in the form of do's and don'ts with
      the hope that these pearls would help others to estabLish and develop their own
      integrative medicine programs within the unique context of their hospitals and
      healthcare systems.

PMID- 25962251
TI  - [Martin Heidegger, beneficence, health, and evidence based medicine-
      contemplations regarding ethics and complementary and alternative medicine].
AB  - Beneficence is considered a core principle of medical ethics. Evidence Based
      Medicine (EBM) is used almost synonymously with beneficence and has become the
      gold standard of efficiency of conventional medicine. Conventional modern
      medicine and EBM in particular are based on what Heidegger called calculative
      thinking, whereas complementary medicine (CM) is often based on contemplative
      thinking according to Heidegger's distinction of different thinking processes. A
      central issue of beneficence is the striving for health and wellbeing. EBM is
      little concerned directly with wellbeing, though it does claim to aim at
      improving quality of life by correcting pathological processes and conditions
      like infectious diseases, ischemic heart disease but also hypertension and
      hyperlipidemia. On the other hand, wellbeing is central to therapeutic efforts of
      CM. Scientific methods to gauge results of EBM are quantitative and based on
      calculative thinking, while results of treatments with CM are expressed in a
      qualitative way and based on meditative thinking. In order to maximize
      beneficence it seems important and feasible to use both approaches, by combining
      EBM and CM in the best interest of the individual patient.

PMID- 25962252
TI  - [Application of bed-side ultrasound tests in wards of internal medicine].
AB  - Bedside sonography by non-radiologists is rapidly expanding, presenting modern
      medicine with challenging professional, medico-legal, financial and logistic
      aspects. In the current article, we reviewed the relevant literature describing
      sonography application by internal medicine practitioners and the obstacles that
      may interfere with large-scale integration of point of care ultrasound imaging.
      In conclusion, we see a great potential for clinical benefit by internists who
      will use bedside sonography and we recommend establishing an official training
      program in the fiell of bedside ultrasonography by internists.

PMID- 25962253
TI  - [SGLT2 inhibitors: a new therapeutic class for the treatment of type 2 diabetes
      mellitus].
AB  - SGLT2 (Sodium Glucose co-Transporter 2 Inhibitors) inhibitors are a new group of
      oral medications for the treatment of type 2 diabetes mellitus patients. These
      medications interfere with the process of glucose reabsorption in the proximal
      convoluted tubules in the kidneys, therefore increasing both glucose and water
      diuresis. SGLT2 inhibitors were found to be effective in lowering HbA1c levels in
      double-blinded studies, both as monotherapy and in combination with other oral
      hypoglycemic medications of various other mechanisms of action. SGLT2 Inhibitors
      are not a risk factor for hypoglycemia and are suitable for combination with
      insulin therapy. Their unique mode of action, relying on glomerular filtration,
      make these medication unsuitable for usage as treatment for type 2 diabetes
      patients who are also suffering from moderate to severe renal failure. Their main
      adverse effects are increased risk for urinary and genital tract infections. The
      following review describes the relevant pathophysiology addressed by these novel
      medications, evidence for efficacy and the safety profile of SGLT2 Inhibitors.

PMID- 25962254
TI  - [Non-invasive assessment of liver fibrosis].
AB  - Chronic liver diseases represent a major public health problem, accounting for
      significant morbidity and mortality worldwide. Prognosis and management of
      chronic liver diseases depend on the amount of liver fibrosis. Liver biopsy has
      long remained the gold standard for assessment of liver fibrosis. Liver biopsy is
      an invasive procedure with associated morbidity, it is rarely the cause for
      mortality, and has a few limitations. During the past two decades, in an attempt
      to overcome the limitations of liver biopsy, non-invasive methods for the
      evaluation of liver fibrosis have been developed, mainly in the field of viral
      hepatitis. This review will focus on different methods available for non-invasive
      evaluation of liver fibrosis including a biological approach which quantifies
      serum levels of biomarkers of fibrosis and physical techniques which measure
      liver stiffness by transient elastography, ultrasound or magnetic resonance based
      elastography, their accuracy, advantages and disadvantages.

PMID- 25962255
TI  - Unexamined assumptions in palliative care.

PMID- 25962256
TI  - Demoralization: a life-preserving diagnosis to make for the severely medically
      ill.

PMID- 25962258
TI  - Unanswered questions in malignant bowel obstruction.

PMID- 25962257
TI  - Palliative care for delirium in patients in the last weeks of life: the final
      frontier.

PMID- 25962259
TI  - What next in refractory breathlessness? Research questions for palliative care.
AB  - Refractory breathlessness is a common and distressing symptom among patients
      receiving palliative care. Improvements in the assessment and management of
      refractory breathlessness are dependent on further research. In this article, we
      have outlined research topics on which to base future work.

PMID- 25962260
TI  - Assessing and classifying cancer pain: can we develop an internationally accepted
      common language?

PMID- 25962261
TI  - Is palliative care at odds with the culture of medicine?

PMID- 25962262
TI  - The third wave of palliative care.

PMID- 25962263
TI  - Palliative care nursing, technology, and therapeutic presence: are they
      reconcilable?

PMID- 25962264
TI  - Intractable wish to die: multiple questions about a challenging issue.

PMID- 25962265
TI  - Palliative care for people with progressive neurological disease: what is the
      role?

PMID- 25962266
TI  - Unanswered questions and barriers to research in the palliative care of motor
      neurone disease patients.

PMID- 25962267
TI  - Patient evaluation and delivery of care at the bedside: increasing well-being.

PMID- 25962268
TI  - Pediatric palliative care in 2014: much accomplished, much yet to be done.

PMID- 25962269
TI  - What is the role and impact of osteoarthritis in the realm of palliative care?

PMID- 25962270
TI  - What is extreme death anxiety and what are its consequences?

PMID- 25962271
TI  - [Cytogenetic effects in Allium schoenoprasum growing on the anthropogenically
      contaminated soil].
AB  - Cytogenetic effects in Allium schoenoprasum meristematic root tip cells grown for
      a year on the territory contaminated with 235U, 238U and 232Th decay series
      radionuclides, heavy metals and As were studied. The area is characterized with
      different concentrations of chemical compounds in soil affecting a toxic element
      migration in biocoenosis. Analysis of the chromosome aberration spectrum showed
      an ambiguous cell response to soil contamination. Within the weighted absorbed
      dose range up to 1.2 Gy the higher the dose the aberrant cell frequency increase
      was shown. But further increase in the dose resulted in a genotoxic effect
      decrease due to high toxic effects of heavy metals and radionuclides in soil.
      This was registered as a mitotic index decrease that can provoke a chromosome
      aberration frequency underestimation and result in erroneous conclusions about
      genotoxic effects in A. schoenoprasum used as a bioindicator.

PMID- 25962272
TI  - [Role of polyalternativeness of animals' ontogeny development in the estimation
      of ionizing radiation consequences].
AB  - The role of polyalternativeness of small mammals' ontogeny development
      (belongings of individuals to alternative pathways of the ontogeny development)
      in the estimation of effects of ionizing radiation is considered. It is shown
      that biological consequences of acute (laboratory experiment) and chronic
      (inhabiting the Eastern Urals Radioactive Trace zone) ionizing radiation in
      rodents significantly depend on the belonging of individuals to the pathway of
      ontogeny. Specificity of the response of the population to acute and chronic
      irradiation is revealed. It is concluded that it is necessary to take into
      account the belonging of individuals to the pathway of ontogeny development in a
      wide spectrum of investigations at the analysis of any biological parameters in
      small rodents in the zones of local technogenic contamination.

PMID- 25962273
TI  - [The level of DNA damage and DNA reparation rate in cells of earthworms sampled
      from natural populations for numerous generations inhabited territories with
      anthropogenically enhanced levels of radionuclides in soil].
AB  - Low doses of ionizing radiation and chemical toxic agent effects on biological
      systems on different organization levels have been studied by numerous
      researchers. But there is a clear lack of experimental data that allow one to
      reveal molecular and cellular adaptations of plants and animals from natural
      populations to adverse effects of environmental factors. The present study was
      aimed to assess genotoxic effects in earthworms Aporrectodea caliginosa Savigny
      and Lumbricus rubellus Hoffmeister sampled from the populations that during
      numerous generations inhabited the territories with a technogeneously enhanced
      content of natural origin radionuclides and heavy metals in soil. The levels
      ofthe DNA damage detected with alkaline and neutral versions of Comet-assay in
      invertebrates from contaminated territories were established not to differ from
      the spontaneous level found in the animals from the reference population. At the
      same time the rate of the DNA damage reparation induced in A. caliginosa sampled
      from the contaminated sites with additional acute gamma-irradiation (4 Gy) was
      found to be considerably higher as compared with earthworms from the reference
      population.

PMID- 25962274
TI  - [Cytogenetic indices for somatic mutagenesis in mammals exposed to chronic low
      dose irradiation].
AB  - We used cytogenetic analysis in the studies of the biological effects of a
      radiation factor of natural and artificial origin (under conditions ofthe 30-km
      exclusion zone ofthe Chernobyl experimental landfills in Ukraine, Belarus and
      Russia). The studies have been performed on various types of mammals: domestic
      animals--cows, pigs, horses and rodents--root voles, the Af mouse line, and
      yellow necked field mouse, bank voles. We found significant changes in the level
      of MN and chromosomal aberrations in the animals that were exposed to the
      conditions of chronic low-dose radiation for a long time (bothin the habitat and
      upon exposure in the Chernobyl zone) regardless of the type of animal and nature
      of contamination.

PMID- 25962275
TI  - [Biochemical parallels of cellular adaptive reactions at chronic low-intensity
      irradiation and action of phitoecdysteroid preparation serpisten].
AB  - Comparison of action of chronic gamma-irradiation at a dose of 22.6 cGy and the
      serpisten substance containing phitoecdysteroids at small doses of 5 and 50 mg/kg
      on biochemical indicators in erythrocytes and tissues of white not purebred mice
      is given. It is established that in both cases there is an increase of minor
      fractions of cardiolipin and phosphatidic acid, lysophosphatidilcholin and a
      share of phospholipids as part of common lipids. Course administration of
      serpisten to rats at the total doses of 12 and 30 mg/kg leads to an increase in
      tissues of thermal shock proteins of family 70 (Hsp70 and Hsc70). Similarity of
      action of ecdysteroid preparations and the influence of stress factors of
      physical nature of low intensity (gamma radiation at a small dose) have been
      detected in mice, which manifest themselves in some chain links of lipid
      peroxidation processes as well as an increase in biosynthesis of thermal shock
      proteins of family 70 (Hsp70 and Hsc70) in rats at administration of serpisten.

PMID- 25962276
TI  - [Effect of soil microflora on 137Cs transition to plants].
AB  - The impact of certain types of microorganisms on 137Cs transfer from the
      substrate into the plant was analyzed in the experiment on artificial mediums. It
      was found that certain types of microorganisms could either reduce or increase
      the ratio of 137Cs transfer from the substrate to the plant. It is shown that
      this property is independent of the localization of the microorganism on the
      surface of the root, for all the analyzed bacteria belonging to the rhizospheric
      group. Azotobacter chroococcum UKM B-6003 stimulated the radionuclide transfer to
      plants up to 1.5 times, while the best bacteria for reducing its accumulation is
      Burkholderia sp IMER-B1 -53 - 1.3 times in comparison with the control. It was
      shown that the strain Bacillus megaterium UKM B-5724 from the collection of the
      Institute of Microbiology and Virology of NASU has a high ability to accumulate
      radionuclides.

PMID- 25962277
TI  - [The radiosensitivity change after low-dose irradiation, possible mechanisms and
      regularities].
AB  - This paper is a short review of literature data and results of our own
      investigation into the adaptive response (AR). It was aimed at the analysis of
      the AR induction, its formation, some mechanisms, its expansion, and
      universality. It is supposed that a lot of mechanisms, a high variability degree,
      the absence of this phenomenon in some individuals, as well as dependence on many
      situations make the AR induction not predictable. Perhaps AR induction is not a
      universal phenomenon in practice, as it was supposed earlier.

PMID- 25962278
TI  - [Morphometric and cytogenetic studies of the follicular epithelium thyroid of
      small mammals under chronic exposure to small doses].
AB  - We have detected the genotoxic effect (increase of micronuclei) after chronic
      exposure to low-level ionizing radiation of the thyroid follicular epithelium of
      the voles living for many generations in the radioactive territory. At the same
      time, we also discovered the stimulating effect of chronic low-level ionizing
      radiation on the activity of morphogenetic processes in the thyroid parenchyma of
      the animals from natural populations (increased micro-follicles). These data were
      confirmed by the experiments; chronic irradiation of the thyroid gland of rats at
      the doses of 5 and 50 cGy revealed an increased induction of micronuclei and the
      increase in the number of small follicles. An increased proliferative potential
      of thyroid may be regarded as a non-specific adaptive response to chronicbody
      exposure to ionizing radiation.

PMID- 25962279
TI  - [Migration in soil and accumulation in plants of peaceful nuclear explosion
      products in Perm region].
AB  - The data on the migration capacity in soil and accumulation of 238Pu, 239, 240Pu,
      137Cs and 90Sr by plants in the area of a peaceful nuclear explosion located in
      the taiga zone are presented. The influence of the soil parameters on the
      distribution and transformation forms of the radionuclides in the podzolic soil
      profile was studied. The major amounts of man-made radionuclides were found in
      the matter of the ground lip. The accumulation parameters of pollutants by plants
      were the highest for the leaves, young branches and conifer of trees.

PMID- 25962280
TI  - [Some aspects of structural alterations of erythrocyte membranes under the effect
      of uranyl chloride at low concentrations].
AB  - The influence of nanomolar concentrations of the uranyl ion on the parameters of
      some membrane structures of rodent erythrocytes (laboratory mice and tundra voles
      -classical objects of radioecological monitoring) was investigated in vitro. A
      high sensitivity of the tundra vole red blood cells to the uranyl influence was
      shown. This fact may be determined by the cross-species difference in the
      membrane structures of erythrocytes--the low sphingomyelin content in tundra
      voles. Investigation into the phospholipid composition of the erythrocytes
      incubated in vitro with uranyl ions demonstrates the absence of the membrane
      lipid component reactions "typical" for the cells circulating in blood and also
      the changes pointing to the initial stages of eryptosis. Latent alterations in
      the membrane structure of red blood cells of both species induced by a short time
      contact with uranyl ions were confirmed by the increase in their sensitivity to
      nonionic detergent Triton X-100 and indicate the changes in orderliness of the
      membrane lipid phase.

PMID- 25962281
TI  - [Role of the tissue antioxidant status in response to chronic irradiation of mice
      during early ontogenesis].
AB  - The response of the liver and blood erythrocyte lipids to the low intensity
      chronic gamma-irradiation action of mice at the dose of 8 cGy during early
      ontogenesis immediately and 7 months after irradiation is studied. The
      maintainance of the changed structural state of the lipid component in liver and
      especially blood erythrocytes which are characterized by a lower antioxidant
      status compared with the liver lipids is revealed during a long time after the
      cessation of irradiation. This confirms the possibility of using blood
      erythrocyte lipids as a perspective model for the estimation of the effects of
      the weak impact of unfavorable factors on the organism.

PMID- 25962282
TI  - [Radiation-induced DNA fragmentation in cells of somatic and generative tissues
      of Drosophila melanogaster].
AB  - The levels of DNA fragmentation (using a neutral version of the "Comet assay"
      method) in the cells of somatic (brain ganglia) and generative (male gonad)
      tissues of the inbred individuals of the Drosophila wild-type developing in
      different conditions of a chronic irradiation were estimated. It was found that
      the radiobiological effect depends on the genotype and cytotype. Irradiation at
      low doses (0.42 mGy/h) induces the DNA damage in somatic cells of all the studied
      lines Drosophila in the same way. With the increase in the intensity of chronic
      irradiation (3.5mGy/h) a significant level of DNA breaks in neuroblasts was
      observed only for Harwich and Oregon-R stocks, in the cells of male gonad--for
      all the studied genotypes.

PMID- 25962283
TI  - [A.H. Sparrow--a classic of radiobiology and radioecology of the twentieth
      century (to the 100th anniversary of his birth)].

PMID- 25962284
TI  - [On the 85th birthday anniversary of Gennady G. Polikarpov (1929-2012)].

PMID- 25962285
TI  - [In memory of Nizametdin Nizametdinovich Isamov].

PMID- 25962286
TI  - [Closed abdominal injury with liver damage].
AB  - An analysis of the treatment results was made in 447 patients with closed
      abdominal injury combined with liver damage. An individualized treatment-and
      diagnostic program considering the data of field surgery--MT scale was applied in
      victims with closed abdominal trauma with liver damage. At the same time the
      classification E. Moore et. all (1990) for liver injuries was used for
      assistance. The indications for endovideosurgical homeosta- sis, a primary suture
      of liver wound and the hepatic resection were determined. The indications for
      packing the liver wound were specialized using strategy of "Damage control". An
      appli- cation of given individualized surgical strategy allowed reduction of the
      lethality level from 32.3% to 17.1% in the case of closed abdominal trauma with
      liver damage.

PMID- 25962287
TI  - [Changes of immune status in acute pancreatitis and its correction].
AB  - Changes of immune status were studied in patients with acute pancreatitis. The
      presence of expressed secondary immunodeficiency was determined in patients with
      acute destructive pancreatitis. The Ronkoleykin immunomodulator was used to
      correct the immune status. The authors obtained the posi- tive results. An
      application of Ronkoleykin immunomodulator allowed decrease of the postoperative
      lethality with a high degree of reliability (p < 0.01).

PMID- 25962288
TI  - [Postoperative hypothyroidism].
AB  - There is a number of factors such as the thyroidectomy and limiting subtotal
      thyroid resection against the background of euthyroidism and initial
      hypothyroidism (in any extent of operation) which leads to the prediction of
      early postoperative hypothyroidism origin during 10 days of the postoperative
      peri- od. The early postoperative hypothyroidism is accompanied by activation
      processes of lipid peroxide oxidation and at the same time by reduction of
      antioxidant protection.

PMID- 25962289
TI  - [Restatement of indications for thyroid nodules biopsy].
AB  - The ultrasonic signs or focal formations have a defining value for indication of
      fine-needle aspiration biopsy of thyroid nodules. The size and dynamics of growth
      aren't so important. The evaluation of indications for performing a thyroid
      nodules biopsy was made in 6403 patients. It was proved that the size of thyroid
      nodules hadn't any value for the indications and technique of aspiration biopsy.
      It was stated that a subjectivity assessment, many errors and parameters variety
      took place in clinical and ultrasound examination in the case of thyroid nodules
      changes. Indications for biopsy based on the size of nodules hadn't any
      theoretical or practical value. The indications according to TIRADS system are
      reasonable. Their application considerably improved obtaining an informative
      material and increased the probability of thyroid tumor detection.

PMID- 25962290
TI  - [Modern technologies and diagnostics in treatment of neuroendocrine tumors of the
      pancreas].
AB  - The article presents the results of investigation and treat- ment of 124 patients
      with neuroendocrine tumors of the pancreas (NET P): insulinima (68 cases),
      gastrinoma (43 cases), rare forms of tumor (13 patients). It was stated that
      clinical manifestations of NET P resembled the signs of neurological and
      gastroentero- logical diseases. Thus, the terms of detection would be prolonged
      during pre-admission stage and this validated the reasonabil- ity of well-timed
      application of current laboratory methods of diagnostics. An appropriate clinic
      neuroendocrine syndrome could be confirmed in 93-96% of patients. The authors
      showed that available diagnostic technique of NET P were the helical computer
      tomography and endoscopic ultrasound study with sen- sitivity 75% and 91%,
      respectively. It was rational to complete study with the data of intraoperative
      sonography for final tumor localization and its assessment in relation to the
      connection with pancreas duct and vessels. At the same time, it could be used in
      case of suspicion to multiple neoplasia. Angiography in combi- nation with
      arterial-stimulated blood sampling from the hepatic vein and positron emission
      tomography with 18-fluorodeoxyglu- cose were the additional methods of
      diagnostics concerning the main forms of limited hyperinsulinism and generalized
      forms of NET P. Immunohistochemical study of removed pancreas tumor was the main
      method of morphological verification of the diagnosis and it's used to develop
      the further strategy of postop- erative treatment for patients. The surgical
      method of treatment of patients with NET P allowed elimination of clinical
      laboratory manifestations of neuroendocrine syndrome and getting general
      cumulative 5-year survival (69.3 +/- 4.7%) of radically operated patients.

PMID- 25962291
TI  - [Value of the index of transversal dislocation of the brain in neurosurgery].
AB  - The complex clinical and radiation examination was made in 135 victims with
      craniocerebral trauma and in 120 patients with primary tumors of the brain. All
      observations evaluated the index of transversal dislocation of the brain. It
      included derivative of volume parameter of intracranial supratentorial
      substratum, the value of dislocation of ventricular system and its width
      relatively to the septum pellucidum and at the same time the state of mind
      according to Glasgow coma scale. High diagnostic informativity of developed and
      certified index of transversal dislocation in dif- ferent intracranial pathology
      allowed using the index for more wide application.

PMID- 25962292
TI  - [Mechanical damage and spontaneous esophageal perforation].
AB  - The article presents the results of treatment of 95 patients with iatrogenic
      damages and perforations caused by other reasons and spontaneous rupture of the
      esophagus. A defect of the esophagus was formed in thoracic part in 67.4% cases.
      Combined suppurative complications such as a neck phlegmon, mediastinitis,
      pleural empyema, pericarditis, pneumonia and lung abscess occurred in prevalent
      majority of patients. Surgical interventions were performed through cervical,
      thoracotomical and laparoscopical accesses. Different plastic methods of covering
      sutures of the esophagus were used in conditions of suppurative inflammation in
      33 patients. An inconsistency of sutures was noted in 6 (18.2%) cases.
      Postoperative lethality consisted of 34.6% in spontaneous rupture of the
      esophagus and it was 11.9% in case of other damages.

PMID- 25962293
TI  - [Diagnostics and treatment of congenital malformations of the lung and
      mediastinum in newborn children and infants].
AB  - The article presents the experience of treatment of newborn children and infants
      with congenital malformations of the lung and mediastinum, which required a
      surgery. Children (138 cases) were treated during recent 18 years. There was a
      prevalence of full-term infants (73%). Fetal malformations were diagnosed in
      prenatal period in majority of cases. Computed tomography was the main method of
      diagnostics after delivery. Children (110 cases) were operated out of 138.
      Children with extrapulmonary sequestration didn't undergo surgery in case of
      absence of clinical manifestations. The authors made a conclusion that
      malformations of the lung and mediastinum should be included in number of
      differentiated diseases in case of respiratory distress syndrome in newborn
      children. The indications to early surgery should be the danger of contamination
      and malignant transformation, presence of intrathoracic tension syndrome in
      neonatal period.

PMID- 25962294
TI  - [Complications of purulent meningoencephalitis in children].
AB  - An analysis of 19 cases of meningoencephalitis was made in infants aged under one
      year old. The disease was complicated by chronic subdural hematomas in 11
      patients and by hydrocephalus in 8 patients. The article presents the strategy,
      treatment results and diagnostic procedures volume. Based on their work, the
      authors made a conclusion that meningoencephalitis required an emergency
      neurosurgical interference in order to avoid complications in convalescence
      period.

PMID- 25962295
TI  - [Bilateral post-traumatic diaphragmatic hernias].
AB  - Traumatic diaphragmatic hernias could be clinically apparent and diagnosed after
      months and years after trauma. Bilateral ruptures of the diaphragm rarely
      appeared. Patients (46 cases) with diaphragmatic hernias were treated at the
      period from 1998 to 2010. The rate of diaphragmatic hernias consisted of 41,3%,
      bilateral post-traumatic hernias was noted in 2.2%. The article presents a follow
      up study of bilateral diaphragmatic hernia, which was formed on the left (after 1
      year) and on the right after 5 years. Diagnosis was supported by radiographic
      contrast research and computed tomography data. The stomach and omentum were
      displaced to the pleural cavity on the left, the transversely colon and omentum
      had a shift on the right. Thoracotomy and diaphragm plasty were performed in both
      cases. Hernial orifice was located in the area of esophageal opening and crura of
      diaphragm. It is necessary to increase clinical suspicion in relation to
      possibility of diaphragmatic hernia origin after severe closed trauma.

PMID- 25962296
TI  - [Comparative research of traumatic injury of open hand-assisted laparoscopic
      anterior resection of the rectum].
AB  - The article made a comparative assessment of traumatic injury of open hand
      assisted laparoscopic anterior resection of the rectum in lateral and spinal
      positions. The presented technique of hand-assisted laparoscopic colon and rectal
      surgery is simple. There are advantages in case of obesity presence (IMT more
      than 30 kg/m2), in significant shortening of the mesocolon and mesentery, high
      fixation of splenic flexure and intimate fixation of the spleen, in case of bad
      preparation of the bowels in partial intestinal obstruction or in case of
      emergency operation, big cancer size, expressed perifocal inflammation. A
      comparative analysis of dynamics of hormone stress content and metabolism
      (cortisol, adrenaline, thyrothrophic hormone) showed their expressed increase in
      blood during operation after traditional surgery. Less stressed reaction was
      noted after hand-assisted surgery, especially in overweight patients. An
      application of low invasive method allowed reduction of hemorrhage, pain
      syndrome, terms of patient's activation and restoration of intestinal motility
      after operation.

PMID- 25962297
TI  - [Initial experience of thoracoscopic lobectomy performance with bronchoplasty].
AB  - The article presents an initial Russian experience of video- thoracoscopic
      bronchoplastic lobectomies performed in 2 clinical cases of centric lung tumors.
      The upper bronchoplastic lobec- tomies with right lymphodissection were carried
      out on two patients in 2012. Complications weren't observed in intraopera- tive
      and postoperative periods. There wasn't relapse during two years after operation.
      Thus, the authors came to conclusion that thoracoscopic bronchoplastic
      lobectomies turned out to be safe and effective interventions in individual
      patients with centric tumor location, which wasn't extended outside mouth of the
      lobar bronchus. The choice of candidates for thoracoscopic bron- choplasty was
      made using video-bronchoscopy, angio-computer tomography of the thorax and PET.
      This allowed avoiding an invasive staging and excluded patients with substantial
      extra- bronchial lesions.

PMID- 25962298
TI  - [Features of the heart wound by non-lethal kinetic weapons].

PMID- 25962299
TI  - [Staging surgery of the patient with complicated locally advanced cancer of
      sigmoid colon].

PMID- 25962300
TI  - [Successful treatment of the child who's got a vast deep burn complicated by
      sepsis, the multiple organ failure and refractory hyperglycemia].

PMID- 25962301
TI  - [Surgery of thyroid gland: objects and unsolved problems].
AB  - The author considers the problems for surgeons such as maintenance of trachea and
      the esophagus integrity, bleeding prophylaxis, damage prevention of recurrent
      nerves and parathyroid glands. The article proposed the measures of the edematous
      syndrome prevention in early postoperative period.

PMID- 25962302
TI  - [Postradial sialozoadenitis in patients with papillary carcinoma of the thyroid
      gland].
AB  - The authors present the results of investigation of 42 patients with salivary
      gland dysfunction after radioactive iodine-131 ablation therapy concerning
      papillary thyroid carcinoma. Clinical manifestations of postradial sialodenitis
      with secretory insufficiency of different degree were revealed. These side
      effects required an application of the special therapy.

PMID- 25962303
TI  - [Surgical treatment of superior thoracic outlet syndrome].
AB  - The authors present immediate and long-term results of treatment of 117 patients
      with superior thoracic outlet syndrome (STOS). There were different reasons for
      compression of neu- rovascular fascicle in outlet of the thorax. The
      costaclavicular syndrome was a reason in 48 patients, additional cervical ribs
      had 36 patients. Skalenus syndrome was noted in 26 cases, rudimentary cervical
      ribs or hypertrophy of cervical vertebrae C7 had 7 patients. Raynaud's syndrome
      took place in 19 cases. The required volume of diagnostic procedures and surgical
      treatment of STOS were determined according to the cause of the syndrome.
      Differentiated approach to the different forms of STOS was used in relation to
      dominant symptoms of the disease and reasons for compression of neurovascular
      fascicle. This allowed getting positive results in majority of patients (90,4%)
      in long- term period.

PMID- 25962304
TI  - [Fournier's gangrene-variety of clinical model of critical states in surgery].
AB  - The investigation based on a retrospective analysis of the treatment results of
      Fournier's gangrene (FG) in 27 patients aged from 34 till 82 years old. There
      were 27 patients. Diseases of colorectal zone were the nosological reasons of FG
      in 15 patients. Diseases of urogenital tract had 10 patients with FG. The
      development of FG was determined by closed trauma (1 patient) and a gunshot wound
      of the perineum and the scrotum in one patient. The slowly progressive (limited)
      forms of the disease were noted in 15 patients, although the rapid progressive
      (extensive) forms were in 12 patients.All the patients had the clinical
      manifestations of the disease and at the same time laboratory indices indicated a
      presence of generalized infection and they were characterized by symptoms of
      systemic inflammatory response syndrome (SIRS). There were 6 patient, who died
      out of 27.The lethality consisted of 22.2%. The reasons of the death were an
      infection-toxic shock (1 case), a progressive endotoxicosis (3 cases) and a
      pulmonary artery thromboembolism (2 cases). The results obtained testified that
      early diagnostics and the active strategy with radical surgical d-bridement of
      necrotic suppurative foci combined with programmed (staged) sanitation
      necrosectomy, complex system of local wound treatment, the rational antibacterial
      therapy, a task-specific and syndrome correction of dyscrasia could be the actual
      ways to improve the treatment results in patients with FG.

PMID- 25962305
TI  - [Vasiliy Ivanovich Kolesov and his part in progress of coronary surgery (to his
      110th birthday)].

PMID- 25962306
TI  - [Intraoperative detection of the sentinel lymph nodes in lung cancer].
AB  - An analysis of the scientific data was made. It was used the literature devoted
      to the intraoperative visualization of the sentinel lymph nodes in patients with
      lung cancer. Correct detection of such lymph nodes with following pathologic
      investigation allowed limiting the volume of lympho-dissection in a number of
      patients. There is the possibility of maximal in-depth study of the sentinel
      lymph nodes by purposeful application of most sensible pathologic and molecular
      methods for detection their micrometastatic lesions. At the same time the
      treatment strategy and prognosis could be determined. The authors present the
      results of an application of dye techniques, radioactive preparation and
      fluorescence imaging for sentinel lymph node detection. Advantages and
      disadvantages of the methods are shown in the article. There are validated the
      prospects of technical development, study of information value of new
      applications and the most perspective method of fluorescence indocyanine green
      visualization by lymph outflow.

PMID- 25962307
TI  - [Application of stem cells in treatment of the patients with critical ischemia of
      the lower extremities].

PMID- 25962308
TI  - [Professor Yuriy Sergeevich Polushin (to his 60th birthday)].

PMID- 25962309
TI  - [Professor Mikhail Dmitrievich Khanevich (to his 60th birthday) (collective of
      authors)].

PMID- 25962310
TI  - [Professor Valeriy Evgenievich Parfyonov (to his 65th birthday)].

PMID- 25962311
TI  - Effects of single-shot and steady-state propofol anaesthesia on rocuronium dose
      response relationship: a randomised trial.
AB  - BACKGROUND: Similar to volatile anaesthetics, propofol may influence
      neuromuscular transmission. We hypothesised that the administration of propofol
      influenced the potency of rocuronium depending on the duration of the
      administration. METHODS: After consent, patients scheduled for elective surgery
      randomly received rocuronium either after induction of anaesthesia with propofol
      (2 min of propofol, n = 36) or after 30 min of propofol infusion (30 min of
      propofol, n = 36). Remifentanil was given in both groups. Neuromuscular
      monitoring was performed by calibrated electromyography. The dose-response
      relationship of rocuronium was determined with a single-bolus technique (0.07,
      0.1, 0.15, 0.2, 0.3 and 0.45 mg/kg rocuronium). The primary endpoints were the
      ED50 and ED95 of rocuronium after 2 and 30 min propofol. Data are presented as
      means with (95% confidence interval). The trial is registered with the Eudra-CT:
      2009-012815-16. RESULTS: A total of 72 patients were included. Time to maximal
      neuromuscular blockade was significantly shorter in patients after 30 min of
      propofol [3.3 min (2.9-3.7)] compared with patients anaesthetised with 2 min of
      propofol [4.6 min (4.0-5.2)]. After 30 min of propofol, the slope of the dose
      response curve was significantly steeper (30 min of propofol: 4.34 [3.62-5.05]; 2
      min of propofol: [3.34 (2.72-3.96)], resulting in lower ED95 values of rocuronium
      (30 min of propofol: 0.287 mg/kg [0.221-0.368]; 2 min of propofol [0.391 mg/kg
      (0.296-0.520)]. The ED50 were not different between groups. CONCLUSION: The
      potency of rocuronium was significantly enhanced after propofol infusion for 30
      min. Estimates of potency those are usually determined during steady-state
      anaesthesia might underestimate rocuronium requirements for endotracheal
      intubation at the time of induction.

PMID- 25962312
TI  - AUTS2 is a potential therapeutic target for pancreatic cancer patients with liver
      metastases.
AB  - Liver metastasis is a common event at the advanced stage of pancreatic
      malignancies. Identification of effective therapeutic targets is crucial for the
      management of pancreatic cancer patients with liver metastases. In this study, we
      show that (A) AUTS2 is overexpressed in liver metastases of pancreatic cancer and
      could be a biomarker for defining cancer subtypes. (B) AUTS2 expression is
      positively correlated with Docetaxel resistance, TGF-beta pathway activation,
      HEDGEHOG and WNT signaling pathway. (C) By building an AUTS2 centered protein
      drug interaction network, we show that AUTS2 might promote chemotherapeutic
      resistance and metastasis by exerting its effect on epithelial-mesenchymal
      transition and WNT signaling pathway. (D) Five drugs that could down regulate the
      expression of AUTS2 were also suggested. These drugs might help in the treatment
      of pancreatic cancer patients at the stage of liver metastasis. In summary, our
      results indicate that AUTS2 is a candidate biomarker for defining liver
      metastasis of pancreatic cancer and directing personalized therapies. 

PMID- 25962313
TI  - Acute but not chronic activation of brain glucagon-like peptide-1 receptors
      enhances glucose-stimulated insulin secretion in mice.
AB  - AIM: To investigate the role of brain glucagon-like peptide-1 (GLP-1) in
      pancreatic beta-cell function. METHODS: To determine the role of brain GLP-1
      receptor (GLP-1R) on beta-cell function, we administered intracerebroventricular
      (i.c.v.) infusions of GLP-1 or the specific GLP-1 antagonist exendin-9 (Ex-9), in
      both an acute and a chronic setting. RESULTS: We observed that acute i.c.v. GLP-1
      infusion potentiates glucose-stimulated insulin secretion (GSIS) and improves
      glucose tolerance, whereas central GLP-1R blockade with Ex-9 impaired glucose
      excursion after a glucose load. Sustained activation of central nervous system
      GLP-1R, however, did not produce any effect on either GSIS or glucose tolerance.
      Similarly, ex vivo GSIS performed in islets from mice chronically infused with
      i.c.v. GLP-1 resulted in no differences compared with controls. In addition, in
      mice fed a high-fat diet we observed that acute i.c.v. GLP-1 infusion improved
      glucose tolerance without changes in GSIS, while chronic GLP-1R activation had no
      effect on glucose homeostasis. CONCLUSIONS: Our results indicate that, under non
      clamped conditions, brain GLP-1 plays a functional neuroendocrine role in the
      acute regulation of glucose homeostasis in both lean and obese rodents.

PMID- 25962314
TI  - Correlation between microsatellite instability status and grading assessed by the
      counting of poorly differentiated clusters in colorectal cancer.

PMID- 25962315
TI  - Outcome of "indefinite for dysplasia" in inflammatory bowel disease: correlation
      with DNA flow cytometry and other risk factors of colorectal cancer.
AB  - Dysplasia that develops in the setting of inflammatory bowel disease precedes
      colorectal cancer (CRC). The category of "indefinite for dysplasia (IND)" is used
      often in equivocal cases, but its clinical significance remains unclear. Flow
      cytometric analysis of DNA content (aneuploidy) has shown some promise in
      stratifying patients into low or high risk of CRC, but there are few reports that
      have specifically evaluated the outcome of IND. As such, we analyzed a series of
      84 IND inflammatory bowel disease patients seen at the University of Washington
      and Harborview Medical Centers from 2003 to 2013 to determine the outcome of IND.
      Hospital electronic medical records were further reviewed to correlate outcome
      with the type of lesion (flat versus polypoid), primary sclerosing cholangitis,
      active inflammation in the area of IND, and DNA flow cytometric data. The data
      show that 13% of IND cases were found to have low-grade dysplasia, whereas only
      2% of IND cases showed advanced neoplasia (high-grade dysplasia or CRC) after a
      mean follow-up of 28 months. The risk of neoplasia was not significantly
      associated with the type of lesion (P = .94 from log-rank test), primary
      sclerosing cholangitis (P = .94), or active inflammation (P = .41) in this
      cohort. However, the finding of DNA aneuploidy at baseline IND was predictive of
      subsequent detection of neoplasia (P = .037). IND patients with abnormal DNA flow
      cytometric results may warrant more careful follow-up, but conversely, IND in the
      setting of normal DNA content may require less frequent surveillance colonoscopy.

PMID- 25962316
TI  - No evidence for external genital morphology affecting cryptic female choice and
      reproductive isolation in Drosophila.
AB  - Genitalia are one of the most rapidly diverging morphological features in
      animals. The evolution of genital morphology is proposed to be driven by sexual
      selection via cryptic female choice, whereby a female selectively uptakes and
      uses a particular male's sperm on the basis of male genital morphology. The
      resulting shifts in genital morphology within a species can lead to divergence in
      genitalia between species, and consequently to reproductive isolation and
      speciation. Although this conceptual framework is supported by correlative data,
      there is little direct empirical evidence. Here, we used a microdissection laser
      to alter the morphology of the external male genitalia in Drosophila, a widely
      used genetic model for both genital shape and cryptic female choice. We evaluate
      the effect of precision alterations to lobe morphology on both interspecific and
      intraspecific mating, and demonstrate experimentally that the male genital lobes
      do not affect copulation duration or cryptic female choice, contrary to long
      standing assumptions regarding the role of the lobes in this model system.
      Rather, we demonstrate that the lobes are essential for copulation to occur.
      Moreover, slight alterations to the lobes significantly reduced copulatory
      success only in competitive environments, identifying precopulatory sexual
      selection as a potential contributing force behind genital diversification. 

PMID- 25962317
TI  - Type II Cortical Dysplasia in Dominant Frontal Lobe Presenting as Gelastic
      Epilepsy.

PMID- 25962318
TI  - Detection and Genome Analysis of a Lineage III Peste Des Petits Ruminants Virus
      in Kenya in 2011.
AB  - In May 2011 in Turkana County, north-western Kenya, tissue samples were collected
      from goats suspected of having died of peste des petits ruminant (PPR) disease,
      an acute viral disease of small ruminants. The samples were processed and tested
      by reverse transcriptase PCR for the presence of PPR viral RNA. The positive
      samples were sequenced and identified as belonging to peste des petits ruminants
      virus (PPRV) lineage III. Full-genome analysis of one of the positive samples
      revealed that the virus causing disease in Kenya in 2011 was 95.7% identical to
      the full genome of a virus isolated in Uganda in 2012 and that a segment of the
      viral fusion gene was 100% identical to that of a virus circulating in Tanzania
      in 2013. These data strongly indicate transboundary movement of lineage III
      viruses between Eastern Africa countries and have significant implications for
      surveillance and control of this important disease as it moves southwards in
      Africa.

PMID- 25962319
TI  - Clinicopathological characteristics and perineural invasion in adenoid cystic
      carcinoma: a systematic review.
AB  - INTRODUCTION: Adenoid cystic carcinoma is the most frequent malignant tumor of
      the submandibular gland and the minor salivary glands. It is a malignant neoplasm
      that, despite its slow growth, shows an unfavorable prognosis. OBJECTIVES: The
      aim of this study was to perform a systematic review of the literature on Adenoid
      cystic carcinoma in the head and neck region and its clinicopathological
      characteristics, with emphasis on the perineural invasion capacity of the tumor.
      METHODS: A systematic search of articles published between January 2000 and
      January 2014 was performed in the PubMed/MEDLINE, SciELO, Science Direct, and
      Scopus databases. RESULTS: Nine articles were selected for this systematic
      review. These demonstrated that the female gender was more often affected and
      that malignant tumors showed a high rate of distant metastasis, recurrence, and a
      low survival rate. The presence of perineural invasion ranged from 29.4% to 62.5%
      and was associated with local tumor recurrence. CONCLUSION: Adenoid cystic
      carcinoma is commonly characterized by the presence of pain, high rate of
      recurrence, metastasis, and a low survival rate. Reporting studies with patient
      follow-up is of utmost importance for a better clinical-pathological
      understanding and to improve the prognosis of this pathology.

PMID- 25962320
TI  - Estimating the secondary attack rate and serial interval of influenza-like
      illnesses using social media.
AB  - OBJECTIVES: Knowledge of the secondary attack rate (SAR) and serial interval (SI)
      of influenza is important for assessing the severity of seasonal epidemics of the
      virus. To date, such estimates have required extensive surveys of target
      populations. Here, we propose a method for estimating the intrafamily SAR and SI
      from postings on the Twitter social network. This estimate is derived from a
      large number of people reporting ILI symptoms in them and?or their immediate
      family members. DESIGN: We analyze data from the 2012-2013 and the 2013-2014
      influenza seasons in England and find that increases in the estimated SAR precede
      increases in ILI rates reported by physicians. RESULTS: We hypothesize that
      observed variations in the peak value of SAR are related to the appearance of
      specific strains of the virus and demonstrate this by comparing the changes in
      SAR values over time in relation to known virology. In addition, we estimate SI
      (the average time between cases) as 2.41 days for 2012 and 2.48 days for 2013.
      CONCLUSIONS: The proposed method can assist health authorities by providing near
      real-time estimation of SAR and SI, and especially in alerting to sudden
      increases thereof.

PMID- 25962321
TI  - Influence of fetuin and hyaluronan on the post-thaw quality and fertilizing
      ability of Holstein bull semen.
AB  - It was determined that fetuin and hyaluronan supplementation did not provide any
      significant effect on the post-thaw subjective and CASA motility percentages and
      sperm motion characteristics, in comparison to the controls (P>0.05). Sperm
      acrosome and total abnormalities were similar in all groups (P>0.05). Groups M
      (hyaluronan+fetuin) and H (hyaluronan) displayed a higher rate of sperm membrane
      integrity, compared to that of Group C (control) (P<0.01). According to the
      results of the comet assay, the lowest percentage of sperm with damaged DNA was
      achieved in Group H, when compared to all of the experimental groups (P<0.01).
      Furthermore, all of the additives resulted in a lower rate of sperm with damaged
      DNA than that of the controls, and thus, reduced DNA damage (P<0.01). For
      pregnancy rates, there were no significant differences between the extender
      groups (P>0.05). MDA formation was found to be lower in Groups M and F (P<0.01).
      In Group M, SOD activity was determined to have significantly increased (23.61+/
      5.62 U/ml) compared to the other groups (P<0.01). All experimental groups had a
      GSH-Px activity higher than that of the control group (P<0.01).

PMID- 25962322
TI  - BAFF receptor and TACI in B-1b cell maintenance and antibacterial responses.
AB  - Although evidence of the protective immunity conferred by B-1b cells (CD19(+)
      B220(+) IgM(hi) Mac1(+) CD5(-)) has been established, the mechanisms governing
      the maintenance and activation of B-1b cells following pathogen encounter remain
      unclear. B cell-activating factor (BAFF) and a proliferation-inducing ligand
      (APRIL) mediate their function in mature B cells through the BAFF receptor
      (BAFFR) and transmembrane activator and CAML interactor (TACI). BAFFR-deficient
      mice have lower numbers of B-1b cells, and this reduction is directly
      proportional to BAFFR levels. The generation of B-1b cells is also dependent on
      the strength of B cell receptor (BCR) signaling. Mice with impaired BCR
      signaling, such as X-linked immunodeficient (xid) mice, have B-1b cell
      deficiency, indicating that both BCR- and BAFFR-mediated signaling are critical
      for B-1b cell homeostasis. Borrelia hermsii induces expansion and persistence of
      B-1b cells in xid mice, and these B-1b cells provide a heightened protective
      response. Toll-like receptor (TLR)-mediated stimulation of xid B cells results in
      a significant increase in TACI expression and restoration of TACI-mediated
      functions. The activation of TLR signaling by B. hermsii and BCR/TLR
      costimulation-mediated upregulation of BAFFR and TACI on B-1b cells suggests that
      B-1b cell maintenance and function following bacterial exposure may depend on
      BAFFR- and TACI-mediated signaling. In fact, the loss of both BAFFR and TACI
      results in a greater impairment in anti-B. hermsii responses compared to
      deficiency of BAFFR or TACI alone.

PMID- 25962323
TI  - Temperamental and socioeconomic factors associated with traumatic dental injuries
      among children aged 0-17 years in the Swedish BITA study.
AB  - AIM: The aim of the study was to identify individual risk factors for traumatic
      dental injuries (TDI) among Swedish children aged 0-17 years. The studied risk
      factors were temperamental reactivity of the child, family structure, parent's
      country of birth, and the socioeconomic status of the family represented by
      parental education and occupation. SUBJECTS AND METHODS: The study included 2363
      children in four different age cohorts at 12 public dental service clinics in
      Sweden, representing different types of demographic areas, both rural and urban.
      Data were collected from parents and children through an interview and
      questionnaires. RESULTS: The more social and active children in the two older age
      cohorts showed less occasions of TDI. Having one parent/guardian protected the
      child from dental injury just as well as two parents/guardians. Parents born
      outside of the Nordic countries showed children with less TDI. Low parental
      education was related to more occasions of TDI among the children. CONCLUSIONS:
      This study has increased the knowledge on certain individual risk factors for
      TDI. To prevent dental injuries, information could be given to families and
      children at risk.

PMID- 25962324
TI  - Prevalence and risk factors of osteoporosis in patients with ankylosing
      spondylitis: a 5-year follow-up study of 504 cases.
AB  - OBJECTIVES: The objective of this study was to assess the prevalence and risk
      factors of osteoporosis (OP) in patients with ankylosing spondylitis (AS).
      METHODS: Demographic and clinical data of 504 AS patients were collected. Bone
      mineral density (BMD) measurements of the lumbar spine, proximal femur and
      forearm were performed by dual-energy x-ray absorptiometry at baseline and follow
      up. 106 cases of sex- and age-matched healthy volunteers were enrolled as normal
      controls. RESULTS: In contrast to normal controls, AS patients displayed a higher
      prevalence of both OP (9.7% vs. 0%) and osteopenia (57.5% vs. 34.9%). The
      prevalence of OP was significantly higher and the BMD were significantly lower in
      patients with elevated erythrocyte sedimentation rate (ESR) or C-reactive protein
      (CRP) than patients with normal ESR and CRP. Juvenile onset, morning stiffness
      lasting over 0.5 hours and elevated ESR levels were risk factors for bone loss at
      the lumbar spine; Male gender, older age, hip involvement and lack of regular
      treatment were risk factors for bone loss at the femur. 173 cases were followed
      up for 1 to 5 years, BMD changes per year at the lumbar spine, femur and forearm
      were 4.8%, 2.7%, and 2.6% respectively. There was no significant difference in
      annual BMD change between patients treated with or without low dose
      glucocorticoids (GCs). Hip involvement and persistent elevated ESR levels, but
      not GCs treatment, were associated with decreased BMD at both the lumbar spine
      and the femur during follow-up in longitudinal regression analysis. CONCLUSIONS:
      High disease activity and hip involvement are risk factors of bone loss in
      patients with AS. Low-dose GCs treatment in AS does not increase the risk of OP.

PMID- 25962325
TI  - Resistin Increases Ectopic Deposition of Lipids Through miR-696 in C2C12 Cells.
AB  - Resistin is associated with ectopic deposition of lipids, and determining its
      developmental and molecular mechanisms may help in the development of novel
      treatments. MicroRNAs (miRNAs) are involved in many physiological and
      pathological processes as negative regulators. We performed mouse liver miRNA
      microarrays to analyze the differences in expression between resistin-treated and
      control mice; the results showed that miR-696 was significantly upregulated by
      resistin. Therefore, we aimed to study whether miR-696 played a role in the
      resistin-induced ectopic deposition of lipids. Quantitative RT-PCR results showed
      that miR-696 was upregulated both in vivo and in vitro, consistent with the
      microarray. We transfected C2C12 cells and used miR-696 mimics and inhibitors to
      assess the role of miR-696 in the resistin-induced ectopic deposition of lipids.
      The overexpression of miR-696 increased the TG content in C2C12 cells and
      decreased the mitochondrial content. Next, a study of miR-696's role in the
      deposition of lipids in C2C12 induced by resistin showed that inhibition of miR
      696 restored the TG content by up to 80%, which suggests that, in C2C12 cells,
      resistin at least partially increases the deposition of lipids through miR-696.
      miR-696 plays a role in the ectopic deposition of lipids induced by resistin in
      skeletal muscle at least partially. 

PMID- 25962326
TI  - Transcriptional Downregulation by Nucleotide Substitution with the Minor Allele
      of rs3760776 Located in the Promoter of FUT6 Gene.
AB  - We examined the promoter activity of an association signal in an upstream region
      of the gene encoding fucosyltransferae 6 (FUT6) identified from a recent
      genomewide association study for the N-glycan level. The luciferase assay using
      reporter constructs with T and C alleles at rs3760776 revealed differential
      promoter activity. The amount of luciferin expressed with the C allele
      corresponded to that without the reporter construct (P > 0.05). On the other
      hand, the expression was dramatically reduced with the T allele (P < 0.05). The
      difference in transcriptional activity between the two alleles was confirmed by
      an electrophoretic mobility shift assay. It demonstrated that the promoter with a
      T allele had a stronger binding affinity to nuclear factors than that with the C
      allele. We concluded that the T allele of rs3760776 might repress the
      transcription of the FUT6 gene. Further studies are warranted to understand its
      underlying mechanism and its influence on susceptibility to potential diseases.

PMID- 25962327
TI  - Anatomic and functional properties of bulboglandularis striated muscle support
      its contribution as sphincter in female rabbit micturition.
AB  - PURPOSE: To determine anatomic and functional properties of the bulboglandularis
      muscle (Bgm) for clarifying its role in micturition in female rabbits. MATERIAL
      AND METHODS: Virgin female rabbits were used to describe the gross anatomy and
      innervation of the Bgm, to determine the effect of the Bgm contraction on
      urethral pressure, and to evaluate the Bgm activity during the induced
      micturition. Both electromyogram and cystometrogram activity were simultaneously
      recorded in urethane-anesthetized rabbits. Bladder function was assessed
      measuring standard urodynamic variables before and after blocking the Bgm
      activity for approaching its contribution to micturition. The relevance of the
      Bgm activation for micturition was approached applying lidocaine injections.
      RESULTS: The Bgm was composed of circularly oriented striated fibers enveloping
      distal urethra and pelvic vagina. Both the venous plexus and urethra were
      comprised by the Bgm contraction induced by electrical stimulation. The Bgm
      showed bursts of tonic activity at the storage phase of micturition that
      gradually decreased until turning off as the onset of the voiding phase. The
      voided volume, the voiding efficiency, the threshold pressure, and the maximal
      pressure were decreased after lidocaine injection. Contrastingly, the threshold
      volume, the residual volume, the voiding duration, and the urethral resistance at
      voiding were increased. CONCLUSIONS: Present anatomical and physiological
      findings support that the Bgm acts as a sphincter during micturition of female
      rabbits. Neurourol. Urodynam. 35:689-695, 2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 25962328
TI  - Plasma ghrelin and liquid gastric emptying in children with functional dyspepsia
      consistent with post-prandial distress syndrome.
AB  - BACKGROUND: Adult studies indicate a role for ghrelin in functional dyspepsia
      (FD) mediated through ghrelin's effect on gastric emptying (GE). This study
      examines the relationship between ghrelin, liquid GE, and pain in children with
      FD. METHODS: Thirteen FD patients reporting symptoms consistent with post
      prandial distress syndrome (PDS) and 17 healthy controls were enrolled. All
      participants received a liquid meal containing (13) C-sodium acetate. Pain
      severity, liquid GE utilizing exhaled (13) CO2 from the sodium acetate breath
      tests (ABT), plasma acyl ghrelin (AG), and des-acyl ghrelin concentrations were
      measured at specific intervals over 240 min following ingestion. KEY RESULTS: FD
      PDS patients demonstrated lower mean baseline AG (14.8 +/- 9.7 vs 27.2 +/- 14.0
      fmol/mL; p = 0.013), AG Cmax (24.6 +/- 8.2 vs 40.5 +/- 16.8 fmol/mL; p = 0.007),
      and AG flux (18.2 +/- 7.8 vs 32.7 +/- 17.3 fmol/mL; p = 0.015) than controls. The
      time to reach maximum exhaled (13) CO2 concentration (T max ) was longer in FD
      patients than controls (47.5 +/- 18.5 vs 35.8 +/- 11.8 min; p = 0.046).
      Significant relationships between ghrelin analyte ratios and ABT parameters were
      largely confined to control participants. CONCLUSIONS & INFERENCES: FD-PDS in
      children is associated with lower fasting and maximum AG concentrations, and
      dampened AG flux. These data suggest a possible role for altered ghrelin
      physiology in the pathogenesis of PDS.

PMID- 25962329
TI  - Comparison of the effects of whole-body cooling during fatiguing exercise in
      males and females.
AB  - The effects of cold stress on exercise performance and fatigue have been
      thoroughly investigated only in males, and thus the general understanding of
      these effects relates only to males. The aim of this study was to determine
      whether whole-body cooling has different effects on performance during fatiguing
      exercise in males and females. Thirty-two subjects (18 males and 14 females) were
      exposed to acute cold stress by intermittent immersion in 14 degrees C water
      until their rectal temperature reached 35.5 degrees C or for a maximum of 170
      min. Thermal responses and motor performance were monitored before and after
      whole-body cooling. Whole-body cooling decreased rectal, muscle and mean skin
      temperatures in all subjects (p<0.05), and these changes did not differ between
      males and females. Cold stress decreased the fatigue index (FI) of a sustained 2
      min maximal voluntary contraction (MVC) only in males (p<0.05). There were no sex
      differences in central and peripheral fatigability, or muscle electromyographic
      activity. This observed sex difference (i.e., body cooling-induced decrease in
      the FI of a sustained MVC in males but not in females) supports the view of sex
      effects on performance during fatiguing exercise after whole-body cooling.

PMID- 25962330
TI  - Converting 2D inorganic-organic ZnSe-DETA hybrid nanosheets into 3D hierarchical
      nanosheet-based ZnSe microspheres with enhanced visible-light-driven
      photocatalytic performances.
AB  - Engineering two-dimensional (2D) nanosheets into three-dimensional (3D)
      hierarchical structures is one of the great challenges in nanochemistry and
      materials science. We report a facile and simple chemical conversion route to
      fabricate 3D hierarchical nanosheet-based ZnSe microspheres by using 2D inorganic
      organic hybrid ZnSe-DETA (DETA = diethylenetriamine) nanosheets as the starting
      precursors. The conversion mechanism involves the controlled depletion of the
      organic-component (DETA) from the hybrid precursors and the subsequent self
      assembly of the remnant inorganic-component (ZnSe). The transformation reaction
      of ZnSe-DETA nanosheets is mainly influenced by the concentration of DETA in the
      reaction solution. We demonstrated that this organic-component depletion method
      could be extended to the synthesis of other hierarchical structures of metal
      sulfides. In addition, the obtained hierarchical nanosheet-based ZnSe
      microspheres exhibited outstanding performance in visible light photocatalytic
      degradation of methyl orange and were highly active for photocatalytic H2
      production. 

PMID- 25962331
TI  - Unanticipated difficult intubation in a patient with juvenile Paget disease.

PMID- 25962332
TI  - Evaluation of three different point-of-care tests for quantitative measurement of
      canine C-reactive protein.
AB  - BACKGROUND: C-reactive protein (CRP) is a major acute phase protein in both
      people and dogs. OBJECTIVE: The objective of this study was to evaluate the
      precision and accuracy of 3 different point-of-care tests (POCT) for canine CRP
      (cCRP) in comparison to a standard ELISA test, and to assess storage stability.
      MATERIAL AND METHODS: Blood samples were collected from 125 dogs (23 healthy and
      102 diseased). Serum cCRP measurements were performed using the TECOmedical AG,
      the EUROLyser Diagnostica, and the LifeAssays POCT. The TECOmedical AG ELISA
      validated for canine serum was used as a reference method. Statistical analyses
      included descriptive statistics, inter assay variance for each POCT, comparison
      of results from each POCT with the ELISA using Spearman's correlation and Bland
      Altman plots, and a t-test to evaluate sample stability. RESULTS: ELISA cCRP
      values ranged from 0.1-4.7 mg/L (median 1.3) in healthy dogs and from 0-282 mg/L
      (median 17.3) in diseased dogs. Spearman's correlation coefficient between ELISA
      and the respective POCT measurements for cCRP concentration was 0.89 for
      TECOmedical, 0.85 for EUROLyser, and 0.97 for LifeAssays. Bias calculated from
      Bland-Altman difference plots was 27.6% for TECOmedical, -14.2% for EUROLyser,
      and -15.7% for LifeAssays. Inter assay reliability was > 0.9 for all POCT. Total
      observed error of the EUROLyser was 28.2% and therefore met the acceptable total
      error of 29.6%. CONCLUSIONS: All POCTs were able to measure cCRP, but precision,
      accuracy, and correlation coefficients varied among the 3 systems. Therefore,
      serial measurements for monitoring of cCRP in dogs should always be performed
      using the same POCT system.

PMID- 25962333
TI  - Low cost production of 3D-printed devices and electrostimulation chambers for the
      culture of primary neurons.
AB  - The analysis of primary neurons is a basic requirement for many areas of
      neurobiology. However, the range of commercial systems available for culturing
      primary neurons is functionally limiting, and the expense of these devices is a
      barrier to both exploratory and large-scale studies. This is especially relevant
      as primary neurons often require unusual geometries and specialised coatings for
      optimum growth. Fortunately, the recent revolution in 3D printing offers the
      possibility to generate customised devices, which can support neuronal growth and
      constrain neurons in defined paths, thereby enabling many aspects of neuronal
      physiology to be studied with relative ease. In this article, we provide a
      detailed description of the system hardware and software required to produce
      affordable 3D-printed culture devices, which are also compatible with live-cell
      imaging. In addition, we also describe how to use these devices to grow and
      stimulate neurons within geometrically constrained compartments and provide
      examples to illustrate the practical utility and potential that these protocols
      offer for many aspects of experimental neurobiology. 

PMID- 25962334
TI  - [Chronic heart failure in the elderly patient].
AB  - The prevalence and incidence of heart failure (HF) is increasing, especially in
      the elderly population, and is becoming a major geriatric problem. Elderly
      patients with HF usually show etiopathogenic, epidemiological, and even clinical
      characteristics significantly different from those present in younger patients.
      Their treatment, however, derives from clinical trials performed with only a few
      elderly subjects. Moreover, beyond the cardiovascular disease itself, it is
      essential to evaluate the patient as a whole, given the interrelationship between
      HF and the characteristic geriatric syndromes of the elderly patient. This review
      examines the peculiarities in the most prevalent "real world" HF patient. 

PMID- 25962335
TI  - [Infectious acute motor-sensory axonal neuropathy in an octogenarian. A case
      report].

PMID- 25962337
TI  - Artificial switchable catalysts.
AB  - Catalysis is key to the effective and efficient transformation of readily
      available building blocks into high value functional molecules and materials. For
      many years research in this field has largely focussed on the invention of new
      catalysts and the optimization of their performance to achieve high conversions
      and/or selectivities. However, inspired by Nature, chemists are beginning to turn
      their attention to the development of catalysts whose activity in different
      chemical processes can be switched by an external stimulus. Potential
      applications include using the states of multiple switchable catalysts to control
      sequences of transformations, producing different products from a pool of
      building blocks according to the order and type of stimuli applied. Here we
      outline the state-of-art in artificial switchable catalysis, classifying systems
      according to the trigger used to achieve control over the catalytic activity and
      stereochemical or other structural outcomes of the reaction. 

PMID- 25962336
TI  - Enzyme-Responsive Delivery of Multiple Proteins with Spatiotemporal Control.
AB  - Orchestrated biological materials such as enzymes and growth factors regulate the
      growth of tissues and organs. A chirality-controlled, single-protein technology
      is devised to tailor the spatiotemporally defined delivery of therapeutic
      proteins in response to natural enzymes present at wound sites. Sustained
      delivery of one protein and sequential delivery of two proteins are demonstrated
      for stroke and skin wound healing. 

PMID- 25962339
TI  - Effect of gamma irradiation on the structural stability and functional activity
      of plasma-derived IgG.
AB  - Plasma-originated commercial intravenous immunoglobulin, which is used for a
      variety of clinical purposes, has been studied to determine the effect of virus
      inactivating doses of gamma irradiation on the structural-functional
      characteristics of the protein. A detailed analysis has been performed in
      response to a concern that the use of conventional gamma irradiation may damage
      biologically active proteins. The results demonstrate that although gamma
      irradiation of the IgG may have some impact on protein structure, the damage can
      be reduced or even prevented by appropriate irradiation conditions. At the
      virucidal dose of gamma irradiation (50 kGy) and a temperature of -80  degrees C,
      the integrity of the polypeptide chain of immunoglobulin and the secondary
      structure of IgG can be completely protected, while conformational changes in
      tertiary structure are significantly minimized to a level that preserves
      functional activity. The irradiated IgG retains specific antigen-binding
      properties and F(c)-binding activity, indicating that the conformational
      integrity of the most important structural regions is not affected by gamma
      irradiation. These results present strong evidence that gamma irradiation
      treatment can be effectively implemented for inactivation of pathogens in IgG
      solutions that are used for intravenous injection.

PMID- 25962340
TI  - An integrative review of complementary and alternative medicine use for back
      pain: a focus on prevalence, reasons for use, influential factors, self-perceived
      effectiveness, and communication.
AB  - BACKGROUND CONTEXT: Back pain is the most prevalent of musculoskeletal
      conditions, and back pain sufferers have been identified as high users of
      complementary and alternative medicine (CAM). Despite lacking evidence, CAM
      treatments (e.g., acupuncture, chiropractic, and massage) and CAM products (eg,
      vitamins, supplements, and aromatherapy oils) for back pain care have become
      widely available internationally, and CAM use by back pain sufferers has become a
      significant health service issue. However, to date, there has been no integrative
      review on CAM use for back pain. PURPOSE: This study aims to conduct an
      integrative review on CAM use for back pain focusing on prevalence of use,
      commonly used CAM, characteristics of users, factors influencing decision making,
      self-perceived effectiveness, and communication with health-care providers. STUDY
      DESIGN/SETTING: The study is based on an integrative literature review. METHODS:
      A comprehensive search of international literature from 2000 to 2014 in MEDLINE,
      CINHAL, AMED, DARE, EMBASE, ExceptaMedica, psycINFO, and SCOPUS databases was
      conducted. The search was limited to peer-reviewed articles published in English
      language and reporting empirical research findings on CAM use for back pain.
      RESULTS: The review reveals a considerable variation in prevalences of CAM use
      for back pain internationally. Acupuncture, chiropractic, osteopathy, and massage
      therapy are the commonly used CAM treatments besides a range of self-prescribed
      CAM, and back pain sufferers use CAM alongside conventional medical treatments.
      Female gender, chronicity of back pain, and previous exposure to CAM are key
      predictors of CAM use for back pain as highlighted from the reviewed literature.
      Family, friends, and recommendation by doctors appear to influence decision
      making on CAM use for back pain. The review reveals that users of CAM for back
      pain tend to report CAM as beneficial, but there is little knowledge on
      communication between CAM users with back pain and health-care providers about
      such use. Existing literature is largely based on the research investigating CAM
      use for back pain among a range of other health conditions. Further rigorous
      research is needed to investigate the use of a wider range of CAM treatments,
      particularly self-prescribed CAM for back pain. CONCLUSIONS: The review findings
      provide insights for health-care providers and policy makers on the range of CAM
      treatments used by back pain sufferers. Conventional medical and CAM
      practitioners should be aware of back pain sufferers' decision making regarding a
      range of CAM treatments and be prepared to communicate with patients on safe and
      effective CAM treatments for back pain.

PMID- 25962342
TI  - Boronic Acid Functionalized Aza-Bodipy (azaBDPBA) based Fluorescence Optodes for
      the Analysis of Glucose in Whole Blood.
AB  - A near-infrared fluorescent dye (aza-bodipy or azaBDPBA) functionalized with
      boronic acid groups was synthesized for the preparation of optodes to measure
      glucose in 40-fold diluted whole blood. Boronic acid groups as an electron
      deficient group on aza-bodipy was reacted with hydrogen peroxide into an electron
      rich phenolic group leading to the red-shift of emission wavelength from 682 to
      724 nm. The emission in near-infrared region offered a low level of background
      interference from whole blood. Also, the dual-wavelength emission guaranteed our
      probe to measure glucose in whole blood accurately after the conversion of
      glucose into hydrogen peroxide using glucose oxidase. The measuring range of
      glucose from 0.2 to 200 mM in the buffer was achieved with high selectivity. To
      facilitate the blood test, the probe was immobilized into thin hydrophobic
      polymer films to prepare the disposal glucose optode, which could detect glucose
      in the solution from 60 MUM to 100 mM. The concentration of glucose in 40-fold
      diluted whole blood was determined using our optode and the reference method,
      respectively. The consistence in the concentration obtained from these two assays
      revealed that our azaBDPBA-based optodes were promising for the clinic assay of
      glucose in the whole blood. 

PMID- 25962338
TI  - Single-molecule super-resolution imaging of chromosomes and in situ haplotype
      visualization using Oligopaint FISH probes.
AB  - Fluorescence in situ hybridization (FISH) is a powerful single-cell technique for
      studying nuclear structure and organization. Here we report two advances in FISH
      based imaging. We first describe the in situ visualization of single-copy regions
      of the genome using two single-molecule super-resolution methodologies. We then
      introduce a robust and reliable system that harnesses single-nucleotide
      polymorphisms (SNPs) to visually distinguish the maternal and paternal homologous
      chromosomes in mammalian and insect systems. Both of these new technologies are
      enabled by renewable, bioinformatically designed, oligonucleotide-based
      Oligopaint probes, which we augment with a strategy that uses secondary
      oligonucleotides (oligos) to produce and enhance fluorescent signals. These
      advances should substantially expand the capability to query parent-of-origin
      specific chromosome positioning and gene expression on a cell-by-cell basis. 

PMID- 25962341
TI  - Bar shoes and ambient temperature are risk factors for exercise-induced pulmonary
      haemorrhage in Thoroughbred racehorses.
AB  - REASONS FOR PERFORMING STUDY: Ambient temperature has been identified as a risk
      factor for exercise-induced pulmonary haemorrhage (EIPH) in racing Thoroughbreds.
      This warranted a more expansive investigation of climatic conditions on the
      incidence and severity of EIPH. The impact of other variables such as the type of
      bit used, tongue ties and nonstandard shoes has not been reported and also
      warrant investigation. OBJECTIVES: To examine the effect of various climatic
      variables as contributing risk factors for EIPH. Other previously uninvestigated
      variables as well as standard track and population factors will also be examined.
      STUDY DESIGN: Cross-sectional study. METHODS: Thoroughbred racehorses competing
      at metropolitan racetracks in Perth, Western Australia were examined 30-200 min
      post race with tracheobronchoscopy. Examination took place at 48 race meetings
      over a 12 month period. Examinations were graded (0-4), independently by two
      experienced veterinarians. Univariable analyses were performed and variables with
      a P<0.25 were entered into a multivariable logistic regression analysis. The
      analysis was performed twice using the presence of blood (EIPH grade 0 vs. grades
      >=1) and EIPH grades <=1 vs. EIPH grades >=2 as dependent variables. RESULTS:
      Exercise-induced pulmonary haemorrhage was diagnosed in 56.6% of observations.
      Lower ambient temperature was significantly associated with EIPH grades >=1 (OR
      0.95; 95% CI 0.93-0.98) and EIPH grades >=2 (OR 0.97; 95% CI 0.94-1.0). Bar shoes
      were significantly associated with EIPH grades >=1 (OR 6.35; 95% CI 2.17-18.54)
      and EIPH grades >=2 (OR 2.72; 95% CI 1.3-5.68). Increasing race distance was
      significantly associated with EIPH grade >=1 and increasing lifetime starts was
      significantly associated with EIPH grade >=2. CONCLUSIONS: Ambient temperature is
      a risk factor for EIPH in Thoroughbred racehorses, with lower temperatures
      associated with increased risk. Bar shoes are a novel risk factor for EIPH in
      this population.

PMID- 25962343
TI  - Increased fat and polyunsaturated fatty acid content in sow gestation diet has no
      effect on gene expression in progeny during the first 7 days of life.
AB  - The 'developmental origins of health and disease' hypothesis proposes not only
      that we are what we eat, but also that we could be what our parents ate. Here, we
      aimed to improve health and performance of young piglets via maternal diets based
      on the hypothesis that maternal nutritional interventions change metabolic
      programming in piglets, reflected by differential gene expression early in life.
      Therefore, sows were fed either a regular diet, based on barley, wheat and wheat
      by-products, sugar beet pulp, palm oil and oilseed meal, or a high-fat (HF) diet
      consisting of the regular diet supplemented with an additional amount of 3.5%
      soybean oil and 1% fish oil at the expense of palm oil and wheat. Performance
      results, physiological parameters and gene expression in liver of piglets and
      blood of piglets and sows at day 7 after farrowing from both diet groups were
      compared. The HF diet tended to enhance growth rate of the offspring in the first
      week of life. No significant differences in gene expression in liver tissue and
      blood could be detected between the two groups, neither with whole-genome
      microarray analysis, nor with gene specific qPCR analysis. In this study, the
      feeding of a high-fat diet with increased amounts of polyunsaturated fatty acid
      (PUFA) to gestating sows under practical farm settings did not induce significant
      changes in gene expression in sows and offspring. 

PMID- 25962344
TI  - [Treatment of the glioma microenvironment].
AB  - Therapeutic concepts for malignant gliomas increasingly target the genetically
      non-transformed tumor stroma rather than the tumor cells themselves. There are
      two particular compartments of the tumor stroma which are currently tackled: the
      vascular compartment by using antiangiogenic treatment with the aim of vascular
      normalization and the immune compartment with the aim of enhancing or inducing
      anti-tumor immunity. Although the vascular endothelial growth factor (VEGF) A
      antibody bevacizumab has not been approved for the treatment of malignant glioma
      in European countries, there is evidence from smaller trials of biological
      efficacy particularly in recurrent disease and the results of a large European
      phase III study testing the clinical efficacy are currently expected.
      Immunotherapies are on the verge of entering the clinical arena with the first
      randomized phase III clinical trials having already been completed. In these
      studies, active vaccination and checkpoint inhibitors which are approved for
      other tumor entities are being tested. This article provides an overview on the
      current antiangiogenic and immunological therapies for gliomas, summarizes the
      results of clinical trials and discusses further developments. 

PMID- 25962345
TI  - [Sociomedical outcome after outpatient withdrawal treatment: Results of a model
      project of integrated care].
AB  - BACKGROUND: Dependence disorders represent a large socioeconomic problem due to
      insufficient and delayed diagnostics and treatment. This study investigated the
      effectiveness of the integrated care concept involving rapid clarification,
      diagnosis, initiation of withdrawal treatment, transfer to addiction
      rehabilitation and abstinence. METHODS: In this prospective observational study
      293 patients with dependency disorders were investigated in an outpatient
      withdrawal treatment concept with respect to the course of the integrated care
      concept, sociodemographic data and other important variables of addiction. In a 2
      year follow-up period abstinence (after t1 = 3, t2 = 12 and t3 = 24 months),
      referral to and beginning addiction rehabilitation were recorded. RESULTS: All
      patients completed the outpatient detoxification treatment concept without
      complications of whom 95.3% were abstinent and 52.9% could be placed in long-term
      treatment (duration 1 year). The 24-month abstinence (DGSS 4) was high but
      decreased significantly over time (t1 = 59.4%, t2 = 50.5%, t3 = 39.7%, p<0.001).
      Placement in a long-term rehabilitation program showed the greatest effect on
      abstinence (p<0.001), followed by treatment duration (p<0.001). The disease
      severity (stress index) showed significantly lower negative effects (p<0.01).
      DISCUSSION: The integrated care concept is an effective outpatient withdrawal
      treatment, despite the methodological limitations. Break points in the addiction
      help system are stabilized and patients can be successfully treated. The results
      are equivalent to a qualified inpatient withdrawal treatment taking the
      recommendations of the Federal Medical Council into consideration.

PMID- 25962346
TI  - [Shock therapy and psychosurgery in the early German Democratic Republic (GDR)].
AB  - Patient files, textbooks and published articles of the time show that the wide
      range of psychiatric therapies of the 1950s and 1960s was also used in the early
      German Democratic Republic (GDR). The use of insulin coma therapy, cardiazol and
      electroconvulsive therapies and especially of leucotomy in the GDR must not only
      be seen in the context of the international development and debate concerning
      these therapies up to the introduction of psychopharmaceutic therapy but also, in
      a similar way as in the Federal Republic of Germany, in relation to the locally
      sometimes different availability of insulin and cardiazol in the post-war period,
      different schools of academic thought and scientific research interest and
      priorities of the clinics concerned. 

PMID- 25962347
TI  - Gamma Knife radiosurgery for medically and surgically refractory prolactinomas:
      long-term results.
AB  - INTRODUCTION: Prolactinomas are the most common functioning pituitary adenomas.
      Dopamine agonists (DA) are generally very effective in treating prolactinomas by
      inducing tumor volume regression and endocrine remission. A minority of patients
      do not respond to DA or are intolerant because of side-effects. Microsurgical
      resection when possible is the next treatment option, but cavernous sinus, dural,
      or bone involvement may not allow for complete resection. OBJECTIVE: We reviewed
      the outcome of patients with medically and surgically refractory prolactinomas
      treated with Gamma Knife radiosurgery (GKRS) during a 22 years follow-up period.
      METHODS: We reviewed the patient database at the University of Virginia Gamma
      Knife center during a 25-year period (1989-2014), identifying 38 patients having
      neurosurgical, radiological and endocrine follow-up. RESULTS: Median age at GKRS
      treatment was 43 years. Median follow-up was 42.3 months (range 6-207.9). 55.3 %
      (n = 21) were taking a dopamine agonist at time of GKRS. 63.2 % (n = 24) had
      cavernous sinus tumor invasion. Endocrine remission (normal serum prolactin off
      of a dopamine agonist) was achieved in 50 % (n = 19). GKRS induced
      hypopituitarism occurred in 30.3 % (n = 10). Cavernous sinus involvement was
      shown to be a significant negative prognosticator of endocrine remission. Taking
      a dopamine agonist drug at the time of GKRS showed a tendency to decrease the
      probability for endocrine remission. CONCLUSION: GKRS for refractory
      prolactinomas can lead to endocrine remission in many patients. Hypopituitarism
      is the most common side effect of GKRS.

PMID- 25962348
TI  - Cyclooxygenase-2--An Imperative Prognostic Biomarker in Oral Squamous Cell
      Carcinoma--An Immunohistochemical Study.
AB  - Oral squamous cell carcinoma (OSCC) is the most common head and neck squamous
      cell carcinoma (HNSCC) with metastasis and tumor recurrence resulting in 90 % of
      cancer associated mortality. COX-2, an inflammatory biomarker, has been shown to
      play a significant role in tumorigenesis of OSCC. To study the expression of COX
      2 in OSCC by immunohistochemistry and investigate its association with the
      clinicopathological parameters including patient survival. A cross sectional
      study was carried out in 75 histologically confirmed cases of OSCC. COX-2
      expression was evaluated by indirect streptavidin biotin method. The expression
      was semi-quantitatively assessed using established criteria. The expression
      profile of COX-2 was correlated with the clinicopathological details like tumor
      size, regional lymphnode metastasis, distant metastasis, clinical stage, local
      recurrence of tumor, histological grade, and survival of patient. Chi square and
      Kaplan Meier statistical tests were applied for assessing this association. COX-2
      expression was absent in normal oral mucosa. Over expression of COX-2 was seen in
      58 out of 75 specimens of OSCC. Overexpression of COX-2 was significantly
      associated with the lymphnode involvement, histological grade, local recurrence
      of tumor and patient survival. COX-2 expression represents an important biomarker
      of prognostic significance that may be used to identify a subset of patients at
      high risk and to predict patient survival.

PMID- 25962349
TI  - Om.breast cancer in very young women aged 25 year-old or below in the center of
      Tunisia and review of the literature.
AB  - Breast cancer in very young women under 40 or 35 years attracted a widespread
      attention. Few studies have focused on women aged below 25 years. The aim of this
      study was to evaluate the situation of breast cancer in women <=25 years in the
      center of Tunisia. Retrospective review from 1993 to 2013. Clinical,
      histopathological, therapeutic and outcome data were recorded. Cases were
      classified into different molecular subtypes based on the immunohistochemistry
      based definitions. The series included 25 patients. The mean duration of symptoms
      was 7.5 months. The most common presenting symptom was a palpable mass. Four
      patients had at least one relative diagnosed with breast cancer. Mammography
      combined with ultrasound was suggestive of malignancy in 60 % of cases. Curative
      surgical treatment could be offered in 19 cases. The mean tumor size was 39 mm.
      Nodal metastases were detected in 9/18 cases. Twenty cases could be classified
      into: luminal A (5 cases), luminal B (6 cases), Her-2 (1 case), triple negative
      (6 cases) and unclassified (2 cases). Two women experienced locoregional
      recurrence and 6 had distant recurrence. Asynchronous contralateral breast cancer
      occurred in one case. The overall survival at 5 and 10 years was 85 and 75 %
      respectively. The survival was significantly lower in grade III tumors (p = 0.04)
      and triple negative tumors (p = 0.03). Breast cancer in women <=25 years is
      uncommon. An adequate medical education of young women and physicians is
      necessary.

PMID- 25962350
TI  - Ferroptosis is Involved in Acetaminophen Induced Cell Death.
AB  - The recently described form of programmed cell death, ferroptosis can be induced
      by agents causing GSH depletion or the inhibition of GPX4. Ferroptosis clearly
      shows distinct morphologic, biochemical and genetic features from apoptosis,
      necrosis and autophagy. Since NAPQI the highly reactive metabolite of the widely
      applied analgesic and antipyretic, acetaminophen induces a cell death which can
      be characterized by GSH depletion, GPX inhibition and caspase independency the
      involvement of ferroptosis in acetaminophen induced cell death has been
      investigated. The specific ferroptosis inhibitor ferrostatin-1 failed to elevate
      the viability of acetaminophen treated HepG2 cells. It should be noticed that
      these cells do not form NAPQI due to the lack of phase I enzyme expression
      therefore GSH depletion cannot be observed. However in the case of acetaminophen
      treated primary mouse hepatocytes the significant elevation of cell viability
      could be observed upon ferrostatin-1 treatment. Similar to ferrostatin-1
      treatment, the addition of the RIP1 kinase inhibitor necrostatin-1 could also
      elevate the viability of acetaminophen treated primary hepatocytes. Ferrostatin-1
      has no influence on the expression of CYP2E1 or on the cellular GSH level which
      suggest that the protective effect of ferrostatin-1 in APAP induced cell death is
      not based on the reduced metabolism of APAP to NAPQI or on altered NAPQI
      conjugation by cellular GSH. Our results suggest that beyond necroptosis and
      apoptosis a third programmed cell death, ferroptosis is also involved in
      acetaminophen induced cell death in primary hepatocytes. 

PMID- 25962351
TI  - Continuous dielectrophoretic particle separation using a microfluidic device with
      3D electrodes and vaulted obstacles.
AB  - This paper reports a microfluidic separation device combining 3D electrodes and
      vaulted obstacles to continuously separate particles experiencing strong positive
      dielectrophoresis (DEP) from particles experiencing weak positive DEP, or from
      particles experiencing negative DEP. The separation is achieved by first focusing
      the particle mixture into a narrow stream by a hydrodynamic focusing flow, and
      then deviating them into different outlets by AC DEP. The vaulted obstacles
      facilitate the separation by both increasing the non-uniformity of the electric
      field, and influencing the particles to move in regions strongly affected by DEP.
      The 3D electrodes give rise to a spatially non-uniform electric field and extend
      DEP effect to the channel height. Numerical simulations are performed to
      investigate the effects of the obstacles on electric field distribution and
      particle trajectories so as to optimize the obstacle height and compare with the
      experimental results. The performance of the device is assessed by separating 25
      MUm gold-coated particles from 10 MUm particles in different flow rates by
      positive DEP and negative DEP, and also separating 25 MUm gold-coated particles
      from yeast cells using only positive DEP. The experimental observation shows a
      reasonable agreement with numerical simulation results. 

PMID- 25962352
TI  - The Effect of Altering Knee Position and Squat Depth on VMO : VL EMG Ratio During
      Squat Exercises.
AB  - BACKGROUND: Patellofemoral pain syndrome is an extremely common condition,
      believed to be caused by altered activation of vastus medialis obliquus (VMO),
      leading to maltracking of the patella. AIM: This study aimed to investigate the
      effect of altering knee movement and squat depth on the ratio of VMO and vastus
      lateralis (VMO : VL) during squat exercises. METHOD: Eighteen (7 male and 11
      female) healthy, asymptomatic participants performed semi-squat exercises with
      three squat depths (20 degrees , 50 degrees  and 80 degrees  of knee flexion)
      while following three knee movement paths (neutral, varus or valgus). Normalized
      VMO : VL ratio from linear envelope surface electromyography was analysed.
      RESULTS: No significant effect was found for gender (p = 0.87), leg dominance (p
      = 0.99) or knee position (p = 0.44). A significant effect was found for squat
      depth (p < 0.001) with both the 50 degrees  and 80 degrees  squats showing
      increases in VMO : VL ratio (p = 0.031 and p = 0.028), respectively. The VMO : VL
      ratio was not influenced by gender, leg dominance or knee position in semi-squat
      exercises. DISCUSSION AND CONCLUSION: Increases in relative VMO activation did
      occur in 'deeper' squat depths (50 degrees  and 80 degrees  knee flexion)
      compared with the 20 degrees  condition. Further research is needed in this area
      concerning the effects of such exercise modifications on a symptomatic
      patellofemoral pain syndrome population. Copyright (c) 2015 John Wiley & Sons,
      Ltd.

PMID- 25962354
TI  - The impact of sensation seeking on the relationship between attention
      deficit/hyperactivity symptoms and severity of Internet addiction risk.
AB  - The aim of this study was to investigate the relationship of attention
      deficit/hyperactivity symptoms (ADHS) with severity of Internet addiction risk
      (SIAR), while controlling the effects of variables such as depression, anxiety,
      anger, sensation seeking and lack of assertiveness among university students.
      Cross-sectional online self-report survey was conducted in two universities among
      a representative sample of 582 Turkish university students. The students were
      assessed through the Addiction Profile Index Internet Addiction Form Screening
      Version (BAPINT-SV), the Psychological Screening Test for Adolescents (PSTA) and
      the Adult Attention deficit/hyperactivity disorder Self-Report Scale (ASRS). The
      participants were classified into the two groups as those with high risk of
      Internet addiction (HRIA) (11%) and those with low risk of Internet addiction
      (IA) (89%). The mean age was lower in the group with HRIA, whereas depression,
      anxiety, sensation seeking, anger, lack of assertiveness and ADHS scores were
      higher in this group. Lastly, a hierarchical regression analysis suggested that
      severity of sensation seeking and ADHS, particularly attention deficiency,
      predicted SIAR. The severity of sensation seeking and ADHS, particularly
      attention deficit symptoms, are important for SIAR. Awareness of sensation
      seeking among those with high ADHS may be important in prevention and management
      of IA among university students. 

PMID- 25962353
TI  - Cloning and molecular characterization of telomerase reverse transcriptase (TERT)
      and telomere length analysis of Peromyscus leucopus.
AB  - Telomerase reverse transcriptase (TERT) is the catalytic subunit of telomerase
      complex that regulates telomerase activity to maintain telomere length for all
      animals with linear chromosomes. As the Mus musculus (MM) laboratory mouse has
      very long telomeres compared to humans, a potential alternative animal model for
      telomere research is the Peromyscus leucopus (PL) mouse that has telomere lengths
      close to the human range and has the wild counterparts for comparison. We report
      the full TERT coding sequence (pTERT) from PL mice to use in the telomere
      research. Comparative analysis with eight other mammalian TERTs revealed a pTERT
      protein considerably homologous to other TERTs and preserved all TERT specific
      sequence signatures, yet with some distinctive features. pTERT displayed the
      highest nucleotide and amino acid sequence homology with hamster TERT. Unlike
      human but similar to MM mice, pTERT expression was detected in various adult
      somatic tissues of PL mice, with the highest expression in testes. Four different
      captive stocks of PL mice and wild-captured PL mice each displayed group-specific
      average telomere lengths, with the longest and shortest telomeres in inbred and
      outbred stock mice, respectively. pTERT showed considerable numbers of synonymous
      and nonsynonymous mutations. A pTERT proximal promoter region cloned was
      homologous among PL and MM mice and rat, but with species-specific features. From
      PL mice, we further cloned and characterized ribosomal protein, large, P0
      (pRPLP0) to use as an internal control for various assays. Peromyscus mice have
      been extensively used for various studies, including human diseases, for which
      pTERT and pRPLP0 would be useful tools. 

PMID- 25962355
TI  - The Chapman psychosis-proneness scales: Consistency across culture and time.
AB  - The purpose of the present study was to examine the factor structure and the
      temporal stability of the Chapman psychosis-proneness scales in a representative
      sample of nonclinical Chinese young adults. The four psychosis-proneness scales
      evaluated were the Perceptual Aberration (PAS), Magical Ideation (MIS), revised
      Social Anhedonia (RSAS), and revised Physical Anhedonia (RPAS) scales. The sample
      consisted of 1724 young adults with a mean age of 18.8 years (S.D. = 0.84). The
      results of the confirmatory factor analyses indicated that the best fitting model
      was a two-factor model with positive schizotypy (PER and MIS) scales and negative
      schizotypy (RSAS and RPAS) scales. The data add to the growing literature
      indicating that the measurement of schizotypal traits is consistent across
      cultures. In addition, the results support the measurement invariance of the
      Chapman psychosis-proneness scales across time, i.e., there was ample evidence of
      test-retest reliability over a test interval of 6 months.

PMID- 25962356
TI  - Electrochemistry, biosensors and microfluidics: a convergence of fields.
AB  - Electrochemistry, biosensors and microfluidics are popular research topics that
      have attracted widespread attention from chemists, biologists, physicists, and
      engineers. Here, we introduce the basic concepts and recent histories of
      electrochemistry, biosensors, and microfluidics, and describe how they are
      combining to form new application-areas, including so-called "point-of-care"
      systems in which measurements traditionally performed in a laboratory are moved
      into the field. We propose that this review can serve both as a useful starting
      point for researchers who are new to these topics, as well as being a compendium
      of the current state-of-the art for experts in these evolving areas. 

PMID- 25962357
TI  - Sentinel node biopsy in vulvar cancer: Implications for staging.
AB  - In 2008, the first Groningen International Study on Sentinel nodes in Vulvar
      cancer (GROINSS-V) showed that omission of inguinofemoral lymphadenectomy is safe
      in patients with early-stage vulvar cancer and a negative sentinel node and it
      simultaneously decreases treatment-related morbidity. An important part of the
      sentinel node procedure is pathologic ultrastaging of the removed sentinel nodes.
      Subsequently, since the introduction of this procedure in the standard care of
      patients with early-stage vulvar cancer, more and smaller inguinofemoral lymph
      node metastases have been diagnosed. The clinical consequences of these
      micrometastases are not clear yet. With increasing size of the sentinel node
      metastasis, chances of non-sentinel node metastases increase and those of
      survival decrease. The size of lymph node metastases is included in the latest
      staging system for vulvar cancer, however at this moment without clinical
      implications. Furthermore, a separate category for micrometastases is not
      incorporated yet. More research is needed to determine the clinical consequences
      of the size of (sentinel) lymph node metastases. 

PMID- 25962358
TI  - Effects of changing climate and cultivar on the phenology and yield of winter
      wheat in the North China Plain.
AB  - Understanding how changing climate and cultivars influence crop phenology and
      potential yield is essential for crop adaptation to future climate change. In
      this study, crop and daily weather data collected from six sites across the North
      China Plain were used to drive a crop model to analyze the impacts of climate
      change and cultivar development on the phenology and production of winter wheat
      from 1981 to 2005. Results showed that both the growth period (GP) and the
      vegetative growth period (VGP) decreased during the study period, whereas changes
      in the reproductive growth period (RGP) either increased slightly or had no
      significant trend. Although new cultivars could prolong the winter wheat
      phenology (0.3~3.8 days per decade for GP), climate warming impacts were more
      significant and mainly accounted for the changes. The harvest index and kernel
      number per stem weight have significantly increased. Model simulation indicated
      that the yield of winter wheat exhibited increases (5.0~19.4%) if new cultivars
      were applied. Climate change demonstrated a negative effect on winter wheat yield
      as suggested by the simulation driven by climate data only (-3.3 to -54.8 kg ha(
      1) year(-1), except for Lushi). Results of this study also indicated that winter
      wheat cultivar development can compensate for the negative effects of future
      climatic change.

PMID- 25962360
TI  - miR-128-3p suppresses hepatocellular carcinoma proliferation by regulating PIK3R1
      and is correlated with the prognosis of HCC patients.
AB  - microRNAs (miRNAs) are known to be involved in the pathogenesis of hepatocellular
      carcinoma (HCC). miR-128-3p was recently reported to be deregulated in several
      types of cancer. However, the biological function and potential mechanisms of miR
      128-3p in HCC remain unknown. In the present study, we found that miR-128-3p was
      frequently downregulated in HCC tissues and cell lines by qRT-PCR analysis.
      Moreover, functional assays showed that overexpression of miR-128-3p markedly
      suppressed HCC cell proliferation by inducing G1 phase cell arrest and migration.
      Mechanistically, miR-128-3p was confirmed to regulate PIK3R1 (p85alpha)
      expression thereby suppressing phosphatidylinositol 3-kinase (PI3K)/AKT pathway
      activation using qRT-PCR and western blot analysis. Furthermore, correlation
      analysis and Kaplan-Meier estimates revealed an inverse correlation between miR
      128-3p and p85alpha as well as a shorter disease-free survival (DFS) period after
      HCC resection in patients with low miR-128-3p expression. Hence, we conclude that
      miR-128-3p, which is frequently downregulated in HCC, inhibits HCC progression by
      regulating PIK3R1 and PI3K/AKT activation, and is a prognostic marker for HCC
      patients.

PMID- 25962361
TI  - Effects of dietary trans-9 octadecenoic acid, trans-11 vaccenic acid and cis-9,
      trans-11 conjugated linoleic acid in mice.
AB  - The aim of the present study was to investigate the effects of dietary trans
      fatty acids in mice. Following the administration of a 0.5/100 g diet of trans-9
      octadecenoic acid (EA), trans-11 vaccenic acid (TVA) or cis-9, trans-11
      conjugated linoleic acid (CLA) for 4 weeks, the body weights and the weights of
      the liver, testis and mediastinal adipose tissue (MAT) of the animals gradually
      decreased (P<0.05). The EA group exhibited the lowest levels of magnesium and
      triglycerides (P<0.05). CLA increased villus length (P<0.05), while EA and TVA
      decreased villus length (P<0.05). The TVA group exhibited the lowest levels of
      low-density lipoprotein and tumor necrosis factor-alpha (P<0.05). Taken together,
      EA, TVA and CLA affected the physiological conditions of mice differently. The
      potential effects of three well-known fatty acids, including trans-9 octadecenoic
      acid (EA), trans-11 vaccenic acid (TVA) and cis-9, trans-11 conjugated linoleic
      acid (CLA), in animals or humans remain to be elucidated. Therefore, in the
      present study, 32 animals were randomly divided into four groups and administered
      a 0.5/100 g diet of EA, TVA or CLA for 4 weeks. The results demonstrated that the
      body weights and the weights of the liver, testis and mediastinal adipose tissue
      (MAT) of the animals gradually decreased (P<0.05). Blood was collected
      individually via the external jugular veins and the EA group exhibited the lowest
      levels of magnesium and triglycerides (P<0.05). CLA increased villus length
      (P<0.05), while EA and TVA decreased villus length (P<0.05). The TVA group
      exhibited the lowest levels of low-density lipoprotein and tumor necrosis factor
      alpha (P<0.05). Taken together, EA, TVA and CLA affected the physiological
      conditions of mice differently and these may further our understanding of the
      various effects of these fatty acids on animals and humans.

PMID- 25962362
TI  - Paraoxonase (PON1) polymorphisms Q192R and L55M are not associated with human
      longevity: A meta-analysis.
AB  - BACKGROUND: Genetic mutations in the paraoxonase 1 (PON1) encoding gene have been
      considered to affect mortality and of these the functional promoter region
      polymorphisms Q192R and L55M are among the most widely studied. OBJECTIVE: The
      aim of this study was to determine whether the Q192R and L55M polymorphisms of
      PON1 can increase susceptibility to longevity. A meta-analysis was performed to
      obtain a comprehensive estimation of the association between Q192R and L55M and
      longevity in long-lived individuals (LLIs) aged 80 years or more. MATERIAL AND
      METHODS: A search was carried out in the PubMed database (from January 2001 to
      May 2014) to obtain data on the role of PON1 polymorphisms in longevity and a
      pooled odds ratio (OR) with a 95% confidence interval (CI) was used to assess the
      associations. RESULTS: The meta-analysis was based on 9 studies of PON1 Q192R and
      5 studies of PON1 L55M that covered a total of 5086 LLIs and 4494 controls.
      Overall, significantly increased risks were not observed for either Q192R or
      L55M. The results of the statistical calculations were as follows: R vs. Q
      (additive model): OR = 1.080, 95% CI = 0.989-1.179, p = 0.088 and RR + RQ vs. QQ
      (dominant model): OR = 1.099, 95% CI = 0.975-1.240, p = 0.124; M vs. L (additive
      model): OR = 0.946, 95% CI = 0.862-1.039, p = 0.245 and MM + ML vs. LL (dominant
      model): OR = 0.951, 95% CI = 0.836-1.081, p = 0.442 for Q192R and L55M,
      respectively. The results did not change with an age cut-off among the LLIs of >=
      93 years. CONCLUSION: No evidence that the Q192R and L55M polymorphisms of PON1
      impacted on the probability of reaching extreme ages was found although this
      cannot be completely ruled out; however, the possibility of population-specific
      effects due to the influence of and interaction between different genes or
      environmental factors could not be ruled out.

PMID- 25962363
TI  - Depression associated with dementia.
AB  - Depression and cognitive disorders, including dementia and mild cognitive
      impairment, are common disorders in old age. Depression is frequent in dementia,
      causing distress, reducing the quality of life, exacerbating cognitive and
      functional impairment and increasing caregiver stress. Even mild levels of
      depression can significantly add to the functional impairment of dementia
      patients and the severity of psychopathological and neurological impairments
      increases with increasing severity of depression. Depressive symptoms may be both
      a risk factor for, as well as a prodrome of dementia. Major depressive syndrome
      of Alzheimer's disease may be among the most common mood disorders of older
      adults. Treating depression is therefore a key clinical priority to improve the
      quality of life both of people with dementia as well as their carergivers.
      Nonpharmacological approaches and watchful waiting should be attempted first in
      patients who present with mild to moderate depression and dementia. In cases of
      severe depression or depression not able to be managed through nonpharmacological
      means, antidepressant therapy should be considered. 

PMID- 25962366
TI  - Investigation of Fragmentation of Tryptophan Nitrogen Radical Cation.
AB  - This work describes investigation of the fragmentation mechanism of tryptophan N
      indolyl radical cation, H3N(+)-TrpN(*) (m/z 204) studied via DFT calculations and
      several gas-phase experimental techniques. The main fragment ion at m/z 131,
      shown to be a mixture of up to four isomers including 3-methylindole (3MI) pi
      radical cation, was found to undergo further loss of an H atom to yield one of
      the two isomeric m/z 130 ions. 3-Methylindole radical cation generated
      independently (via CID of [Cu(II)(terpy)3MI](*2+)) displayed gas-phase reactivity
      partially similar to that of the m/z 131 fragment, further confirming our
      proposed mechanism. CID of deuterated tryptophan N-indolyl radical cation (m/z
      208) suggested that up to six H atoms are involved in the pathway to formation of
      the m/z 131 ion, consistent with hydrogen atom scrambling during CID of
      protonated Trp.

PMID- 25962367
TI  - Gas-Phase Fragmentation of Protonated N,2-Diphenyl-N'-(p
      Toluenesulfonyl)Ethanimidamides: Tosyl Cation Transfer Versus Proton Transfer.
AB  - The gas-phase dissociation chemistry of protonated N,2-diphenyl-N'-(p
      toluenesulfonyl) ethanimidamides was investigated by electrospray ionization mass
      spectrometry in combination with density functional theory calculation. The
      protonated molecules underwent fragmentation via two main competing channels: (1)
      migration of the tosyl cation to the anilinic N atom and the subsequent loss of 2
      phenylacetonitrile to afford protonated N-phenyl p-toluenesulfonamide (m/z 248);
      and (2) transfer of the ionizing proton to the anilinic N atom to give an
      ion/neutral complex of [tosyl cation / 2-phenylacetonitrile] (m/z 272) and the
      subsequent decomposition to yield tosyl cation (m/z 155). To the best of our
      knowledge, the gas-phase tosyl cation transfer has not been reported previously.
      For the para-substituted sulfonamides, the presence of electron-donating groups
      on the anilinic ring inhibits the reaction channel of the tosyl cation migration,
      whereas the presence of electron-withdrawing groups favors this pathway.

PMID- 25962368
TI  - Nd:YAG laser photocoagulation of benign oral vascular lesions: a case series.
AB  - Vascular anomalies of the head and neck are common lesions usually associated
      with functional and/or aesthetic limitations. The aim of the present paper was to
      report a case series of oral vascular malformations treated with Nd:YAG laser
      photocoagulation, highlighting the clinical evolution and post-surgical
      complications. Fifteen patients diagnosed with oral vascular malformations were
      treated with Nd:YAG laser followed by three sessions of biostimulation. None of
      the patients presented post-surgical pain, but 6 of 15 patients (40%) experienced
      minimal post-surgical complications. All cases presented complete resolution of
      the lesions after laser treatment. More importantly, 12 out of 15 (80%) resolved
      after a single session. Low morbidity, minimal patient discomfort, and
      satisfactory aesthetic results point Nd:YAG laser photocoagulation as a promising
      option for the management of benign oral vascular lesions.

PMID- 25962369
TI  - Peer mentoring program in an interprofessional and interdisciplinary curriculum
      in Brazil.
AB  - The Federal University of Sao Paulo, Baixada Santista Campus was founded in 2006
      with five degree-granting programs in physical education, physiotherapy,
      nutrition, psychology, and occupational therapy. The guiding principle behind the
      programs' educational mission was centered on the development of health care
      professionals capable of working in interdisciplinary teams with an emphasis on
      holistic patient care. This pedagogical structure required peer-mentoring
      programs in order to integrate different areas of knowledge and to improve
      learning strategies among new generations of students. The authors' objective in
      the present report is to discuss the strategies and activities of the peer
      mentoring program in histophysiology and gross anatomy in an interdisciplinary
      and interprofessional curriculum. Evaluations by students, mentors and professors
      are presented, along with a statistical analysis of variance comparing student
      performance in the module assessments according to their participation in the
      peer-mentoring activities. The results demonstrated that students who
      participated in peer-mentoring activities enjoyed a higher rate of academic
      success than those who did not participate. In addition, student and mentor
      evaluations of the peer mentoring program were highly positive. The program
      enabled mentors to gain a deeper knowledge of the subjects addressed in the
      learning modules, as well as to develop intrinsic teaching skills during their
      time as mentors. In short, the authors believe that the peer-mentoring program
      has been validated for its effectiveness in raising student academic performance.

PMID- 25962370
TI  - Barcroft's bold assertion: All dwellers at high altitudes are persons of impaired
      physical and mental powers.
AB  - Barcroft's bold assertion that everyone at high altitude has physical and mental
      impairment compared with sea level was very provocative. It was a result of the
      expedition that he led to Cerro de Pasco in Peru, altitude 4300 m. Although it is
      clear that newcomers to high altitude have reduced physical powers, some people
      believe that this does not apply to permanent residents who have been at high
      altitude for generations. The best evidence supports Barcroft's contention,
      although permanent residents often perform better than acclimatized lowlanders.
      Turning to neuropsychological function, newcomers to high altitude certainly have
      some impairment, and there is evidence that the same applies to highlanders.
      However the notion that permanent residents are impaired is anathema to many
      people. For example the eminent Peruvian physician Carlos Monge took great
      exception to Barcroft's remark and even attributed it to the fact that Barcroft
      was suffering from acute mountain sickness when he made it! Monge referred to
      'climatic aggression', by which he meant the negative consequences of the
      inevitable hypoxia of high altitude. Recent technological advances such as oxygen
      enrichment of room air can overcome this 'aggression'. This might be useful in
      some settings at high altitude such as a nursery where newborn babies are cared
      for, and possibly operating rooms where the surgeon's dexterity may be enhanced.
      Other situations might be dormitories, conference rooms, and perhaps some school
      rooms. These constitute possible ways by which the effects of Barcroft's
      assertion might be countered.

PMID- 25962371
TI  - Early MRI finding in adult spinal cord injury without radiologic abnormalities
      does not correlate with the neurological outcome: a retrospective study.

PMID- 25962373
TI  - Tobacco smoke exposure and impact of smoking legislation on rural and non-rural
      hospitality venues in North Dakota.
AB  - The purpose of this cross-sectional study in a stratified random sample of 135
      bars and restaurants in North Dakota was to describe factors that influenced
      tobacco smoke pollution levels in the venues; to compare the quantity of tobacco
      smoke pollution by rurality and by presence of local ordinances; and to assess
      compliance with state and local laws. In data collection in 2012, we measured the
      indoor air quality indicator of particulate matter (2.5 microns aerodynamic
      diameter or smaller), calculated average smoking density and occupant density,
      and determined compliance with state and local smoking ordinances using
      observational methods. As rurality increased, tobacco smoke pollution in bars
      increased. A significant association was found between stringency of local laws
      and level of tobacco smoke pollution, but the strength of the association varied
      by venue type. Compliance was significantly lower in venues in communities
      without local ordinances. Controlling for venue type, 69.2% of smoke-free
      policy's impact on tobacco smoke pollution levels was mediated by observed
      smoking. This study advances scientific knowledge on the factors influencing
      tobacco smoke pollution and informs public health advocates and decision makers
      on policy needs, especially in rural areas.

PMID- 25962372
TI  - Vegetable dishes, dairy products and fruits are key items mediating adequate
      dietary intake for Japanese adults with spinal cord injury.
AB  - STUDY DESIGN: This is a cross-sectional study. OBJECTIVES: The objective of this
      study was to ascertain the essential items mediating adequate dietary intake
      based on the Japanese Food Guide in common among the transtheoretical model
      (TTM), self-efficacy (SE) and outcome expectancy (OE). SETTING: Members of the
      organization Spinal Injuries Japan. METHODS: We posted a questionnaire survey to
      2731 community-dwelling Japanese adults with spinal cord injury (SCI), and
      responses from 841 individuals were analyzed. Food intake was assessed as the
      frequency scores of 10 food items eaten in a daily diet in Japan. The
      correlations between the frequency scores of food intake and TTM, SE and OE were
      determined by binominal logistic regression analysis. RESULTS: The frequency
      scores of food intake were significantly associated with 'To eat vegetable dishes
      (dishes made mainly from vegetables or potatoes) not less than twice a day', 'To
      eat green/yellow vegetables not less than twice a day', 'To eat dairy products
      not less than once a day' and 'To eat fruits not less than once a day' in TTM.
      'To eat vegetable dishes (dishes made mainly from vegetables or potatoes) not
      less than twice a day', 'To eat dairy products not less than once a day' and 'To
      eat fruits not less than once a day' were significantly associated with the
      frequency scores of food intake in SE. In OE, no differences were shown.
      CONCLUSION: This study finds that vegetable dishes, dairy products and fruits are
      the key items mediating adequate dietary intake. Dietary guidelines promoting the
      intake of these dishes for SCI individuals are needed.

PMID- 25962374
TI  - Sex Differences in Experimentally Induced Colitis in Mice: a Role for Estrogens.
AB  - Sex differences have been found in the incidence and progression of inflammatory
      bowel diseases (IBD) such as ulcerative colitis and Crohn's disease. The reported
      differences in observational studies are controversial, and the effects of sex
      hormones on the pathogenesis of IBD are not clear. The aim of this study was to
      analyze sex differences in the progression of experimentally induced colitis.
      Experimental colitis was induced in adult mice by adding 2% dextran sodium
      sulfate (DSS) into drinking water. Male and female mice were used as intact,
      gonadectomized, and supplemented with either estradiol or testosterone. In
      comparison to males, female mice with induced colitis had significantly longer
      colon (p < 0.05), lower decrease in body weight (p < 0.001), and lower stool
      consistency score (p < 0.05). Histopathological analysis showed less inflammatory
      infiltrates (p < 0.001) and crypt damage (p < 0.001) in female mice. Female mice
      with colitis had also lower concentration of TNF-alpha in colon homogenates (p <
      0.01). Supplementation with estradiol in ovariectomized mice ameliorated the
      severity of colitis. Female mice are partially protected against chemically
      induced colitis. This protection seems to be mediated by estradiol.

PMID- 25962376
TI  - Hydrophobic-hydrophilic monolithic dual-phase layer for two-dimensional thin
      layer chromatography coupled with surface-enhanced Raman spectroscopy detection.
AB  - Hydrophobic-hydrophilic monolithic dual-phase plates have been prepared by a two
      step polymerization method for two-dimensional thin-layer chromatography of low
      molecular-weight compounds, namely, several dyes. The thin 200 MUm poly(glycidyl
      methacrylate-co-ethylene dimethacrylate) layers attached to microscope glass
      plates were prepared using a UV-initiated polymerization method within a simple
      glass mold. After cutting and cleaning the specific area of the layer, the
      reassembled mold was filled with a polymerization mixture of butyl methacrylate
      and ethylene dimethacrylate and subsequently irradiated with UV light. During the
      second polymerization process, the former layer was protected from the UV light
      with a UV mask. After extracting the porogens and hydrolyzing the poly(glycidyl
      methacrylate-co-ethylene dimethacrylate) area, these two-dimensional layers were
      used to separate a mixture of dyes with great difference in their polarity using
      reversed-phase chromatography mode within the hydrophobic layer and then
      hydrophilic interaction chromatography mode along the hydrophilic area. In the
      latter dimension only the specific spot was developed further. Detection of the
      separated dyes could be achieved with surface-enhanced Raman spectroscopy. 

PMID- 25962375
TI  - Hypertonic Saline (NaCl 7.5%) Reduces LPS-Induced Acute Lung Injury in Rats.
AB  - Acute respiratory distress syndrome (ARDS) is the most severe lung inflammatory
      manifestation and has no effective therapy nowadays. Sepsis is one of the main
      illnesses among ARDS causes. The use of fluid resuscitation is an important
      treatment for sepsis, but positive fluid balance may induce pulmonary injury. As
      an alternative, fluid resuscitation with hypertonic saline ((HS) NaCl 7.5%) has
      been described as a promising therapeutical agent in sepsis-induced ARDS by the
      diminished amount of fluid necessary. Thus, we evaluated the effect of hypertonic
      saline in the treatment of LPS-induced ARDS. We found that hypertonic saline
      (NaCl 7.5%) treatment in rat model of LPS-induced ARDS avoided pulmonary function
      worsening and inhibited type I collagen deposition. In addition, hypertonic
      saline prevented pulmonary injury by decreasing metalloproteinase 9 (MMP-9)
      activity in tissue. Focal adhesion kinase (FAK) activation was reduced in HS
      group as well as neutrophil infiltration, NOS2 expression and NO content. Our
      study shows that fluid resuscitation with hypertonic saline decreases the
      progression of LPS-induced ARDS due to inhibition of pulmonary remodeling that is
      observed when regular saline is used.

PMID- 25962377
TI  - Sensitive fluorimetric assays for alpha-glucosidase activity and inhibitor
      screening based on beta-cyclodextrin-coated quantum dots.
AB  - A fluorescence method was established for a alpha-glucosidase activity assay and
      inhibitor screening based on beta-cyclodextrin-coated quantum dots. p
      Nitrophenol, the hydrolysis product of the alpha-glucosidase reaction, could
      quench the fluorescence of beta-cyclodextrin-coated quantum dots via an electron
      transfer process, leading to fluorescence turn-off, whereas the fluorescence of
      the system turned on in the presence of alpha-glucosidase inhibitors. Taking
      advantage of the excellent properties of quantum dots, this method provided a
      very simple, rapid and sensitive screening method for alpha-glucosidase
      inhibitors. Two alpha-glucosidase inhibitors, 2,4,6-tribromophenol and acarbose,
      were used to evaluate the feasibility of this screening model, and IC50 values of
      24 MUM and 0.55 mM were obtained respectively, which were lower than those
      previously reported. The method may have potential application in screening alpha
      glucosidase inhibitors.

PMID- 25962379
TI  - A whole body vibration perception map and associated acceleration loads at the
      lower leg, hip and head.
AB  - Whole-body vibration (WBV) training has become popular in recent years. However,
      WBV may be harmful to the human body. The goal of this study was to determine the
      acceleration magnitudes at different body segments for different frequencies of
      WBV. Additionally, vibration sensation ratings by subjects served to create
      perception vibration magnitude and discomfort maps of the human body. In the
      first of two experiments, 65 young adults mean (+/- SD) age range of 23 (+/- 3.0)
      years, participated in WBV severity perception ratings, based on a Borg scale.
      Measurements were performed at 12 different frequencies, two intensities (3 and 5
      mm amplitudes) of rotational mode WBV. On a separate day, a second experiment (n
      = 40) included vertical accelerometry of the head, hip and lower leg with the
      same WBV settings. The highest lower limb vibration magnitude perception based on
      the Borg scale was extremely intense for the frequencies between 21 and 25 Hz;
      somewhat hard for the trunk region (11-25 Hz) and fairly light for the head (13
      25 Hz). The highest vertical accelerations were found at a frequency of 23 Hz at
      the tibia, 9 Hz at the hip and 13 Hz at the head. At 5 mm amplitude, 61.5% of the
      subjects reported discomfort in the foot region (21-25 Hz), 46.2% for the lower
      back (17, 19 and 21 Hz) and 23% for the abdominal region (9-13 Hz). The range of
      3-7 Hz represents the safest frequency range with magnitudes less than 1 g(*)sec
      for all studied regions. 

PMID- 25962378
TI  - Achilles tendon displacement patterns during passive stretch and eccentric
      loading are altered in middle-aged adults.
AB  - The purpose of this study was to investigate middle-age effects on Achilles
      displacement patterns under passive stretch and eccentric loading. Healthy young
      (24.1 +/- 1.4 years, n = 9) and middle-aged (49.0 +/- 3.1 years, n = 9) adults
      were positioned prone and the ankle was cyclically dorsiflexed (0.5 Hz, 25
      degrees  range) during passive stretch and active lengthening. Achilles
      displacements were tracked in cine ultrasound using 2D speckle tracking.
      Displacements were found to be non-uniform, with mid and deep portions of the
      tendon displacing more than superficial portions. However, the degree of non
      uniformity was significantly reduced in middle-aged adults, suggesting a
      potential age-related reduction in inter-fascicle sliding or a shift in loading
      sharing between plantarflexors. Eccentric loading reduced displacement
      magnitudes, likely reflecting distal tendon stretch induced via active muscle
      contractions. Changes in tendon displacement with active loading were greater in
      middle-aged adults, which could reflect greater tendon compliance. The observed
      age-related changes in Achilles tendon behavior may have implications for both
      plantarflexor performance and injury risk.

PMID- 25962380
TI  - Site-dependent and interindividual variations in Denonvilliers' fascia: a
      histological study using donated elderly male cadavers.
AB  - BACKGROUND: Site-dependent and interindividual histological differences in
      Denonvilliers' fascia (DF) are not well understood. This study aimed to examine
      site-dependent and interindividual differences in DF and to determine whether
      changes in the current approach to radical prostatectomy are warranted in light
      of these histological findings. METHODS: Twenty-five donated male cadavers (age
      range, 72-95 years) were examined. These cadavers had been donated to Sapporo
      Medical University for research and education on human anatomy. Their use for
      research was approved by the university ethics committee. Horizontal sections (15
      cadavers) or sagittal sections (10 cadavers) were prepared at intervals of 2-5 mm
      for hematoxylin and eosin staining. Elastic-Masson staining and
      immunohistochemical staining were also performed, using mouse monoclonal anti
      human alpha-smooth muscle actin to stain connective tissues and mouse monoclonal
      anti-human S100 protein to stain nerves. RESULTS: We observed that DF consisted
      of disorderly, loose connective tissue and structures resembling "leaves", which
      were interlacing and adjacent to each other, actually representing elastic or
      smooth muscle fibers. Variations in DF were observed in the following: 1)
      configuration of multiple leaves, including clear, unclear, or fragmented behind
      the body and tips of the seminal vesicles, depending on the site; 2) connection
      with the lateral pelvic fascia at the posterolateral angle of the prostate
      posterior to the neurovascular bundles, being clear, unclear, or absent; 3) all
      or most leaves of DF fused with the prostatic capsule near the base of the
      seminal vesicles, and periprostatic nerves were embedded in the leaves at the
      fusion site; and 4) some DF leaves fused with the prostatic capsule anteriorly
      and/or the fascia propria of the rectum posteriorly. CONCLUSIONS: Site-dependent
      and interindividual variations in DF were observed in donated elderly male
      cadavers. All or most DF leaves are fused with the prostatic capsule near the
      base of the seminal vesicles and some DF leaves are fused with the fascia propria
      of the rectum posterior. Based on our results, surgeons should be aware of
      variations and search for them to create a suitable dissection plane to avoid
      iatrogenic positive margins and rectal injury.

PMID- 25962381
TI  - Identification and characterization of expressed retrotransposons in the genome
      of the Paracoccidioides species complex.
AB  - BACKGROUND: Species from the Paracoccidioides complex are thermally dimorphic
      fungi and the causative agents of paracoccidioidomycosis, a deep fungal infection
      that is the most prevalent systemic mycosis in Latin America and represents the
      most important cause of death in immunocompetent individuals with systemic
      mycosis in Brazil. We previously described the identification of eight new
      families of DNA transposons in Paracoccidioides genomes. In this work, we aimed
      to identify potentially active retrotransposons in Paracoccidioides genomes.
      RESULTS: We identified five different retrotransposon families (four LTR-like and
      one LINE-like element) in the genomes of three Paracoccidioides isolates.
      Retrotransposons were present in all of the genomes analyzed. P. brasiliensis and
      P. lutzii species harbored the same retrotransposon lineages but differed in
      their copy numbers. In the Pb01, Pb03 and Pb18 genomes, the number of LTR
      retrotransposons was higher than the number of LINE-like elements, and the LINE
      like element RtPc5 was transcribed in Paracoccidioides lutzii (Pb01) but could
      not be detected in P. brasiliensis (Pb03 and Pb18) by semi-quantitative RT-PCR.
      CONCLUSION: Five new potentially active retrotransposons have been identified in
      the genomic assemblies of the Paracoccidioides species complex using a combined
      computational and experimental approach. The distribution across the two known
      species, P. brasiliensis and P. lutzii, and phylogenetics analysis indicate that
      these elements could have been acquired before speciation occurred. The presence
      of active retrotransposons in the genome may have implications regarding the
      evolution and genetic diversification of the Paracoccidioides genus.

PMID- 25962382
TI  - Intraoperative extracorporeal autogenous irradiated tendon grafts for functional
      limb salvage surgery of soft tissue sarcomas of the wrist and hand.
AB  - BACKGROUND: In patients with soft tissue sarcoma of the wrist and hand, limb
      salvage operation is extremely challenging for surgeons in attempting a complete
      tumor resection with negative surgical margins. In this study, we report four
      patients with soft tissue sarcoma of the wrist and hand treated by limb salvage
      operation with intraoperative extracorporeal autogenous irradiated tendon grafts.
      METHODS: The patients were all male, and the mean age at the time of surgery was
      45 years. Histological diagnoses included clear cell sarcoma in two patients,
      synovial sarcoma in one, and angiosarcoma in one. All four patients had high
      grade tumors, wherein three had American Joint Committee on Cancer (AJCC) stage
      III disease and one with AJCC stage IV disease. The tumors were resected en bloc
      with involved tendons. The tendons were isolated from the resected tissues,
      irradiated ex vivo, and re-implanted into the host tendons. In one patient, the
      bone was resected additionally because of tumor invasion to the bone. Hand
      function was evaluated using Musculoskeletal Tumor Society (MSTS) rating system.
      RESULTS: Of the four patients, three died of distant metastatic disease. The
      remaining patient lives and remains disease-free. The mean follow-up period was
      33 months. One patient had local recurrence outside the irradiated graft at 20
      months after surgery. The functional rating was 22. Lower scores were seen in
      patients with reconstruction of flexor tendons than extensor tendons.
      CONCLUSIONS: Limb salvage operation with intraoperative extracorporeal autogenous
      irradiated tendon grafts is an acceptable method in selected patients with soft
      tissue sarcoma of the wrist and hand.

PMID- 25962383
TI  - Immunomodulation by lipid emulsions in pulmonary inflammation: a randomized
      controlled trial.
AB  - INTRODUCTION: Acute respiratory distress syndrome (ARDS) is a major cause of
      mortality in intensive care units. As there is rising evidence about immuno
      modulatory effects of lipid emulsions required for parenteral nutrition of ARDS
      patients, we sought to investigate whether infusion of conventional soybean oil
      (SO)-based or fish oil (FO)-based lipid emulsions rich in either n-6 or n-3 fatty
      acids, respectively, may influence subsequent pulmonary inflammation. METHODS: In
      a randomized controlled, single-blinded pilot study, forty-two volunteers
      received SO, FO, or normal saline for two days. Thereafter, volunteers inhaled
      pre-defined doses of lipopolysaccharide (LPS) followed by bronchoalveolar lavage
      (BAL) 8 or 24 h later. In the murine model of LPS-induced lung injury a possible
      involvement of resolvin E1 (RvE1) receptor ChemR23 was investigated. Wild-type
      and ChemR23 knockout mice were infused with both lipid emulsions and challenged
      with LPS intratracheally. RESULTS: In volunteers receiving lipid emulsions, the
      fatty acid profile in the plasma and in isolated neutrophils and monocytes was
      significantly changed. Adhesion of isolated monocytes to endothelial cells was
      enhanced after infusion of SO and reduced by FO, however, no difference of
      infusion on an array of surface adhesion molecules was detected. In neutrophils
      and monocytes, LPS-elicited generation of pro-inflammatory cytokines increased in
      the SO and decreased in the FO group. LPS inhalation in volunteers evoked an
      increase in neutrophils in BAL fluids, which decreased faster in the FO group.
      While TNF-alpha in the BAL was increased in the SO group, IL-8 decreased faster
      in the FO group. In the murine model of lung injury, effects of FO similar to the
      volunteer group observed in wild-type mice were abrogated in ChemR23 knockout
      mice. CONCLUSIONS: After infusion of conventional lipid emulsions, leukocytes
      exhibited increased adhesive and pro-inflammatory features. In contrast, FO-based
      lipid emulsions reduced monocyte adhesion, decreased pro-inflammatory cytokines,
      and neutrophil recruitment into the alveolar space possibly mediated by ChemR23
      signaling. Lipid emulsions thus exert differential effects in human volunteers
      and mice in vivo. TRIAL REGISTRATION: DRKS00006131 at the German Clinical Trial
      Registry, 2014/05/14.

PMID- 25962385
TI  - Transplantation of human amnion mesenchymal cells attenuates the disease
      development in rats with collagen-induced arthritis.
AB  - OBJECTIVES: Human amnion mesenchymal cells (hAMCs), isolated from the amniotic
      membrane of human placenta, are a unique population of mesenchymal stem cells
      (MSCs). Recent studies indicated that hAMCs had immunosuppressive functions and
      might be used in treatment of some autoimmune diseases. The aim of this study is
      to explore the feasibility of using hAMCs for treatment rats with collagen
      induced arthritis (CIA), a classic animal model for human rheumatoid arthritis.
      METHODS: SD rats were immunised with type II collagen and Freund's incomplete
      adjuvant. hAMCs were injected intraperitoneal when arthritis had become
      established. The arthritis was evaluated macroscopically and microscopically.
      Serum levels of IFN-gamma, TNF-alpha, SOD, MDA, GSH-Px and T-AOC were detected by
      commercially assay kits. CD4+/CD8+ T-cell ratio in peripheral blood was examined
      by flow cytometry. Proliferation of splenocytes was evaluated using MTT assay.
      RESULTS: The results demonstrated that application of hAMCs significantly
      ameliorated severity of arthritis and decreased the histopathological changes in
      CIA rats. Consistently, production of proinflammatory cytokines such as IFN-gamma
      and TNF-alpha was dramatically inhibited. Moreover, hAMCs exerted anti-oxidative
      capacity by significantly raising the levels of SOD, GSH-Px, T-AOC and lowering
      the level of MDA. In addition, hAMCs also remarkably restored CD4+/CD8+ T-cell
      ratio and induced hyporesponsiveness of T lymphocytes by inhibiting their active
      proliferation. Finally, hAMCs had no obvious side effect on CIA rats.
      CONCLUSIONS: In conclusion, our results indicated that hAMCs could attenuate the
      disease development in rats with CIA, which might be a promising cell source for
      therapy of rheumatoid arthritis.

PMID- 25962384
TI  - 4'-O-methylhonokiol increases levels of 2-arachidonoyl glycerol in mouse brain
      via selective inhibition of its COX-2-mediated oxygenation.
AB  - BACKGROUND AND PURPOSE: 4'-O-methylhonokiol (MH) is a natural product showing
      anti-inflammatory, anti-osteoclastogenic, and neuroprotective effects. MH was
      reported to modulate cannabinoid CB2 receptors as an inverse agonist for cAMP
      production and an agonist for intracellular [Ca2+]. It was recently shown that MH
      inhibits cAMP formation via CB2 receptors. In this study, the exact modulation of
      MH on CB2 receptor activity was elucidated and its endocannabinoid substrate
      specific inhibition (SSI) of cyclooxygenase-2 (COX-2) and CNS bioavailability are
      described for the first time. METHODS: CB2 receptor modulation ([35S]GTPgammaS,
      cAMP, and beta-arrestin) by MH was measured in hCB2-transfected CHO-K1 cells and
      native conditions (HL60 cells and mouse spleen). The COX-2 SSI was investigated
      in RAW264.7 cells and in Swiss albino mice by targeted metabolomics using LC
      MS/MS. RESULTS: MH is a CB2 receptor agonist and a potent COX-2 SSI. It induced
      partial agonism in both the [35S]GTPgammaS binding and beta-arrestin recruitment
      assays while being a full agonist in the cAMP pathway. MH selectively inhibited
      PGE2 glycerol ester formation (over PGE2) in RAW264.7 cells and significantly
      increased the levels of 2-AG in mouse brain in a dose-dependent manner (3 to 20
      mg kg(-1)) without affecting other metabolites. After 7 h from intraperitoneal
      (i.p.) injection, MH was quantified in significant amounts in the brain
      (corresponding to 200 to 300 nM). CONCLUSIONS: LC-MS/MS quantification shows that
      MH is bioavailable to the brain and under condition of inflammation exerts
      significant indirect effects on 2-AG levels. The biphenyl scaffold might serve as
      valuable source of dual CB2 receptor modulators and COX-2 SSIs as demonstrated by
      additional MH analogs that show similar effects. The combination of CB2 agonism
      and COX-2 SSI offers a yet unexplored polypharmacology with expected synergistic
      effects in neuroinflammatory diseases, thus providing a rationale for the diverse
      neuroprotective effects reported for MH in animal models.

PMID- 25962386
TI  - When natural mutants do not fit our expectations: the intriguing case of patients
      with XRCC4 mutations revealed by whole-exome sequencing.

PMID- 25962387
TI  - Gates funds surveillance site to prevent next big epidemic.

PMID- 25962388
TI  - School Nurses' Professional Practice in the HPV Vaccine Decision-Making Process.
AB  - Because U.S. human papillomavirus (HPV) vaccination rates remain low, we
      evaluated school nurses' knowledge, attitudes, perceptions of their role as
      opinion leaders, self-efficacy, intention, and professional practice regarding
      the HPV vaccine and determined if these variables influenced their professional
      practice concerning the HPV vaccine. We utilized a cross-sectional design by
      recruiting Ohio Association of School Nurses (OASN) members. Participants (n =
      145) completed a paper survey during the OASN annual conference. Structural
      equation modeling was used to examine the proposed model. Our model yielded a
      well-fitting solution, chi2 = 1.118 (degrees of freedom = 2, p = .57). Knowledge
      had positive effects on intention and self-efficacy. Attitude had a positive
      effect on perception of role as opinion leaders. Intention to provide HPV vaccine
      education had a positive effect on professional practice. To develop school
      nurses' practice, interventions should center on increasing knowledge, attitudes,
      and intention toward providing HPV vaccine education.

PMID- 25962389
TI  - Who knows the risk? Challenge to improve education and knowledge infrastructure
      for workers and companies.

PMID- 25962390
TI  - Dosing time-dependent changes in the analgesic effect of pregabalin on diabetic
      neuropathy in mice.
AB  - Patients with diabetes often develop peripheral nerve complications, including
      numbness and pain in the extremities. Diabetes-induced peripheral neuropathic
      pain is characterized by hypersensitivity to innocuous stimuli, known as tactile
      allodynia. Pregabalin (PGN) is currently used to treat diabetes-induced
      peripheral neuropathy and alleviates allodynia. In the present study, we
      demonstrated that the antiallodynic effect of PGN on diabetic mice was modulated
      by circadian changes in its intestinal absorption. A single intraperitoneal
      administration of 200 mg/kg streptozotocin (STZ) to mice induced type I diabetic
      pathologic changes that were accompanied by tactile allodynia. The intensity of
      tactile allodynia in STZ-induced diabetic mice was alleviated by the oral
      administration of PGN; however, the antiallodynic effect varied according to its
      dosing time. The analgesic effect of PGN was enhanced by its administration at
      the times of day when its intestinal absorption was accelerated. Organic cation
      transporter novel type 1 (Octn1) mediated the uptake of PGN into intestinal
      epithelial cells. The expression of Octn1 in the small intestine of STZ-induced
      diabetic mice oscillated in a circadian time-dependent manner. This oscillation
      in Octn1 appeared to cause the time of day-dependent changes in the intestinal
      absorption of PGN. Similar dosing time dependencies of the antiallodynic effect
      of PGN and oscillation in Octn1 expression were also detected in type II diabetic
      db/db mice. These results suggested that the dosing time-dependent differences in
      the analgesic effect of PGN were attributable to circadian oscillations in the
      intestinal expression of Octn1 and also that optimizing its dosing schedule may
      assist in achieving rational pharmacotherapy for diabetes-induced peripheral
      neuropathic pain. 

PMID- 25962391
TI  - Humanized thymidine kinase-NOG mice can be used to identify drugs that cause
      animal-specific hepatotoxicity: a case study with furosemide.
AB  - Interspecies differences have limited the predictive utility of toxicology
      studies performed using animal species. A drug that could be a safe and effective
      treatment in humans could cause toxicity in animals, preventing it from being
      used in humans. We investigated whether the use of thymidine kinase (TK)-NOG mice
      with humanized livers could prevent this unfortunate outcome (i.e., "rescue" a
      drug for use in humans). A high dose of furosemide is known to cause severe liver
      toxicity in mice, but it is a safe and effective treatment in humans. We
      demonstrate that administration of a high dose of furosemide (200 mg/kg i.p.)
      causes extensive hepatotoxicity in control mice but not in humanized TK-NOG mice.
      This interspecies difference results from a higher rate of production of the
      toxicity-causing metabolite by mouse liver. Comparison of their survival curves
      indicated that the humanized mice were more resistant than control mice to the
      hepatotoxicity caused by high doses of furosemide. In this test case, humanized
      TK-NOG mouse studies indicate that humans could be safely treated with a high
      dose of furosemide. 

PMID- 25962392
TI  - Fish Intake and Venous Thromboembolism: A Systematic Literature Review.
AB  - Diet plays an important role in modulating the risk of arterial and venous
      thrombosis. Several lines of evidence attest that consumption of fish and its
      compounds, especially omega-3 fatty acids, may be effective to decrease the
      cardiovascular risk. Since the pathogenesis of arterial and venous thrombosis
      share some common aspects, we performed a systematic review of published clinical
      studies that investigated the association between fish intake and venous
      thrombosis. An electronic search was carried out in Medline, Scopus, and ISI Web
      of Science using the key words "fish" OR "seafood" AND "venous thromboembolism"
      OR "deep vein thrombosis" OR "pulmonary embolism", with no language or date
      restriction. Overall, 6 studies (5 prospective and 1 case-control) were finally
      identified. In only 1 small case-control study, a larger intake of total fish was
      found to be negatively associated with the risk of venous thromboembolism. No
      association was found in 4 large prospective studies, whereas a positive
      association was observed in the remaining. No substantial difference was also
      noticed between intake of fatty or lean fish. Taken together, the current
      epidemiological evidence does not support the existence of a significant effect
      of total fish consumption on the risk of venous thromboembolism. 

PMID- 25962393
TI  - A Comparison of Dabigatran With Warfarin for Stroke Prevention in Atrial
      Fibrillation in an Asian Population.
AB  - BACKGROUND: The Asian population with atrial fibrillation (AF) have a higher risk
      of stroke than the caucasian population and a higher risk of intracranial
      bleeding when anticoagulated with warfarin. There are few real-world studies
      comparing the efficacy of non-vitamin K antagonist oral anticoagulants (NOACs)
      and warfarin among Asian patients to assess its outcomes of ischemic stroke and
      hemorrhagic stroke. METHODS: A retrospective cohort study of 1000 patients on
      dabigatran and warfarin from 2009 to 2013. RESULTS: Data were available for 500
      patients on dabigatran and 500 patients on warfarin. The average follow-up
      duration was 315 +/- 280 days in the dabigatran group and 355 +/- 232 in the
      warfarin group. The time in therapeutic range (TTR) was 53.2% in the warfarin
      treated group, with 32.8% of patients in the subtherapeutic international
      normalized ratio range of <2. None of the patients in the dabigatran group had
      ischemic cerebrovascular accident (CVA) compared to 4 (0.8%) patients in the
      warfarin group, hazard ratio (HR) 0.13, P = .3. There was 1 (0.2%) patient in
      both dabigatran and warfarin groups with hemorrhagic CVA (HR 1.16, P = .92).
      There were 3 (0.6%) patients with major bleeding in the dabigatran group compared
      to 2 (0.4%) patients in the warfarin group (HR 1.57, P = .59). CONCLUSION: There
      were similar rates of efficacy for outcomes of ischemic CVA, hemorrhagic CVA, and
      bleeding when comparing dabigatran with warfarin. Our study shows that despite
      similar efficacy, suboptimal TTR rates and inconveniences with warfarin
      demonstrate that NOACs are preferred for stroke prevention in AF.

PMID- 25962395
TI  - Urinary microRNA-30a-5p is a potential biomarker for ovarian serous
      adenocarcinoma.
AB  - MicroRNAs (miRNAs) can serve as biomarkers in human cancer. To determine the
      clinical value of urinary miRNAs for ovarian serous adenocarcinoma, we collected
      urine samples from 39 ovarian serous adenocarcinoma patients, 26 patients with
      benign gynecological disease and 30 healthy controls. The miRNA microarray data
      showed that only miR-30a-5p was upregulated and 37 miRNAs were downregulated in
      the urine samples of ovarian serous adenocarcinoma patients, when compared to
      healthy controls, which was confirmed after conducting quantitative PCR. The
      upregulation of urinary miR-30a-5p was closely associated with early stage of
      ovarian serous adenocarcinoma as well as lymphatic metastasis. Receiver operator
      characteristic (ROC) analysis demonstrated the potential use of urinary miR-30a
      5p as a diagnostic marker for ovarian serous adenocarcinoma. Furthermore, a lower
      urine level of miR-30a-5p was found in 20 gastric cancer and 20 colon carcinoma
      patients when compared to ovarian serous adenocarcinoma, suggesting that the
      upregulation of urinary miR-30a-5p may be specific for ovarian serous
      adenocarcinoma. miR-30a-5p was also upregulated in ovarian serous adenocarcinoma
      tissues and cell lines, while urinary miR-30a-5p from ovarian cancer patients was
      notably reduced following the surgical removal of ovarian serous adenocarcinoma,
      suggesting that urinary miR-30a-5p was derived from the ovarian serous
      adenocarcinoma tissue. Notably, miR-30a-5p was concentrated with exosomes from
      the ovarian cancer cell supernatant or urine from ovarian serous adenocarcinoma
      patients, supporting a pathway for excretion into the urine. The results also
      showed that the knockdown of miR-30a-5p significantly inhibited the proliferation
      and migration of ovarian cancer cells. In summary, to the best of our knowledge,
      the present study provided the first evidence of increased miR-30a-5p in the
      urine of ovarian serous adeno-carcinoma patients, while the inhibition of miR-30a
      5p suppressed the malignant phenotypes of ovarian cancer in vitro. Therefore, miR
      30a-5p serves as a promising diagnostic and therapeutic target for ovarian serous
      adenocarcinoma.

PMID- 25962394
TI  - Ozone Inhalation Impairs Coronary Artery Dilation via Intracellular Oxidative
      Stress: Evidence for Serum-Borne Factors as Drivers of Systemic Toxicity.
AB  - Ambient ozone (O3) levels are associated with cardiovascular morbidity and
      mortality, but the underlying pathophysiological mechanisms driving
      extrapulmonary toxicity remain unclear. This study examined the coronary vascular
      bed of rats in terms of constrictive and dilatory responses to known agonists
      following a single O3 inhalation exposure. In addition, serum from exposed rats
      was used in ex vivo preparations to examine whether bioactivity and toxic effects
      of inhaled O3 could be conveyed to extrapulmonary systems via the circulation. We
      found that 24 h following inhalation of 1 ppm O3, isolated coronary vessels
      exhibited greater basal tone and constricted to a greater degree to serotonin
      stimulation. Vasodilation to acetylcholine (ACh) was markedly diminished in
      coronary arteries from O3-exposed rats, compared with filtered air-exposed
      controls. Dilation to ACh was restored by combined superoxide dismutase and
      catalase treatment, and also by NADPH oxidase inhibition. When dilute (10%) serum
      from exposed rats was perfused into the lumen of coronary arteries from
      unexposed, naive rats, the O3-induced reduction in vasodilatory response to ACh
      was partially recapitulated. Furthermore, following O3 inhalation, serum
      exhibited a nitric oxide scavenging capacity, which may partially explain blunted
      ACh-mediated vasodilatory responses. Thus, bioactivity from inhalation exposures
      may be due to compositional changes of the circulation. These studies shed light
      on possible mechanisms of action that may explain O3-associated cardiac morbidity
      and mortality in humans. 

PMID- 25962396
TI  - Establishment and characterization of triple drug resistant head and neck
      squamous cell carcinoma cell lines.
AB  - Resistance to chemotherapy leading to poor outcome and survival remains a
      challenge for developing strategies for therapeutic interventions in all types of
      cancer, including head and neck cancer. In vitro chemoresistant cell line models
      are an indispensable resource towards delineating the mechanisms involved in drug
      resistance/response and for the development of novel drugs. Current treatment for
      head and neck cancer includes chemotherapy with cisplatin, docetaxel and 5
      fluorouracil (5-FU) and the response rates to these drugs in patients is 60-80%.
      The present study aimed to generate head and neck cancer triple drug-resistant
      cell lines in an effort towards elucidating the mechanisms underlying
      chemoresistance and providing a resourceful tool for drug design. Using two head
      and neck squamous cell carcinoma cell lines, Hep-2 (larynx) and CAL-27 (oral
      cavity), the present study sequentially exposed these cells to increasing
      concentrations of the combination of docetaxel, cisplatin and 5-FU (TPF) to
      generate triple drug-resistant cells, termed Hep-2 TPF resistant (TPFR) and CAL
      27 TPFR. The effect of the drug treatments on the cell viability, apoptosis, cell
      cycle and the expression of genes associated with multidrug resistance were
      analyzed in the parental cells and drug-resistant counterparts.

PMID- 25962397
TI  - Ethnobotanical survey of medicinal dietary plants used by the Naxi People in
      Lijiang Area, Northwest Yunnan, China.
AB  - BACKGROUND: Food and herbal medicinal therapy is an important aspect of Chinese
      traditional culture and traditional Chinese medicine. The Naxi are indigenous
      residents of the Ancient Tea Horse Road, and the medicine of the Naxi integrates
      traditional Chinese, Tibetan, and Shamanic medicinal systems, however, little is
      known about the medicinal dietary plants used by the Naxi people, or their
      ethnobotanical knowledge. This is the first study to document the plant species
      used as medicinal dietary plants by the Naxi of the Lijiang area. METHODS:
      Ethnobotancial surveys were conducted with 89 informants (35 key informants) from
      2012 to 2013. Three different Naxi villages were selected as the study sites.
      Literature research, participatory investigation, key informant interviews, and
      group discussions were conducted to document medicinal dietary plants and the
      parts used, habitat, preparation methods, and function of these plants. The
      fidelity level (FL) was used to determine the acceptance of these medicinal
      dietary plants. Voucher specimens were collected for taxonomic identification.
      RESULTS: Surveys at the study sites found that 41 ethnotaxa corresponded to 55
      botanical taxa (species, varieties, or subspecies) belonging to 24 families and
      41 genera. Overall, 60 % of documented plants belonged to seven botanical
      families. The most common families were Compositae (16.4 %) and Rosaceae (10.9
      %). Roots (34.1 %) were the most common part used. Wild-gathered (68.3 %), semi
      domesticated (17.1 %), and cultivated (14.6 %) were the most common habitats of
      medicinal dietary plants. Stewing plants with meat was the most common
      preparation and consumption method. The plants were used to treat 21 major health
      conditions; alleviating fatigue (42.8 %) was the most common. The maximum FL of
      100 was found for 68.3 % of the medicinal dietary plants CONCLUSIONS: The
      medicinal dietary plants used by the Naxi people are diverse and are used to
      treat a wide spectrum of body disorders. Further studies focusing on safety,
      detoxification, and nutritional value of the plants should be conducted to allow
      them to be used to improve health and prevent diseases in modern society.

PMID- 25962399
TI  - Two emerging topics regarding long-range physical signaling in neurosystems:
      Membrane nanotubes and electromagnetic fields.
AB  - In this review paper, an overview is given of two emerging research topics that
      address the importance of long-range physical signaling in living biosystems. The
      first topic concerns the biophysical principles and the physiological
      significance of long-range cell-to-cell signaling through electrical signals
      facilitated by membrane nanotubes (MNTs) (also called "tunneling nanotubes"),
      namely long membrane extensions that connect cells, discovered about 10 years
      ago. This review paper looks at experimental results that showed electrical
      signals being propagated through MNTs, and that MNT-mediated electrical coupling
      between brain cells involves activation of low-voltage-gated calcium channels.
      The significance of electrical cell-to-cell coupling through MNT for neuronal
      communication is discussed. The second topic deals with endogenous
      electromagnetic fields generated by nerve cells. The review concludes that these
      fields are not just an "epiphenomenon" but play a fundamental role in neuronal
      processes. For example, electromagnetic fields from brain cells feed back to
      their generating cells and to other cells (ephaptic coupling) and, for example,
      modulate the spiking timing of them. It is also discussed that cell membranes of
      neurons have specific resonance properties which possibly determine the impact of
      endogenous electric field fluctuations with respect to field strength and
      frequency. In addition, it is reviewed how traveling and standing waves of the
      endogenous electromagnetic field produced by neuronal and non-neuronal cells may
      play an integral part in global neuronal network dynamics. Finally, an outlook is
      given on which research questions should be addressed in the future regarding
      these two topics. 

PMID- 25962398
TI  - Depression increases the onset of cardiovascular disease over and above other
      determinants in older primary care patients, a cohort study.
AB  - BACKGROUND: To determine if major depressive disorder (MDD) in older primary care
      patients is an independent risk factor for cardiovascular events. METHODS: A
      cohort of 143 primary care patients with depression and 139 non-depressed
      controls without depression (both aged over 55 years, matched for age and gender)
      from the Netherlands was evaluated for 2 years. MDD was diagnosed according to
      DSM-IV-criteria. During the follow-up period, information was collected on
      physical health, depression status and behavioural risk factors. CVD end points
      were assessed with validated annual questionnaires and were crosschecked with
      medical records. RESULTS: Thirty-four participants experienced a cardiovascular
      event, of which 71% were depressed: 27/134 with MDD (20.1%) and 9/137 controls
      (6.6%). MDD was associated with a hazard ratio of 2.83 (p value 0,004, 95% CI
      1.32 to 6.05) for cardiovascular events. After adjustment for cardiovascular
      medication, the hazard ratio was 2.46 (95% CI 1.14 to 5.30). CONCLUSIONS: In a 2
      year follow-up period, baseline MDD increased the risk for CVD in older primary
      care patients compared with controls, over and above well-known cardiovascular
      risk factors.

PMID- 25962400
TI  - Reversal of neuromuscular block with sugammadex: a comparison of the corrugator
      supercilii and adductor pollicis muscles in a randomized dose-response study.
AB  - BACKGROUND: Neuromuscular monitoring using the corrugator supercilii muscle is
      associated with a number of challenges. The aim of this study was to assess
      reversal of a rocuronium-induced neuromuscular blockade with sugammadex according
      to monitoring either using the corrugator supercilii muscle or the adductor
      pollicis muscle. We hypothesized that a larger dose of sugammadex would be
      required to obtain a train-of-four (TOF) ratio of 1.0 with the corrugator
      supercilii muscle than with the adductor pollicis muscle. METHODS: Forty patients
      aged 20-60 years and 40 patients aged >= 70 years were enrolled. After induction
      of anesthesia, we recorded the corrugator supercilii muscle response to facial
      nerve stimulation and the adductor pollicis muscle response to ulnar nerve
      stimulation using acceleromyography. All patients received 1 mg/kg rocuronium.
      When the first twitch (T1) of TOF recovered to 10% of control values at the
      corrugator supercilii, rocuronium infusion was commenced to maintain a T1 of 10%
      of the control at the corrugator supercilii. Immediately after discontinuation of
      rocuronium infusion, 2 mg/kg or 4 mg/kg of sugammadex was administered. The time
      for recovery to a TOF ratio of 1.0 and the number of patients not reaching a TOF
      ratio of 1.0 by 5 min at each dose and muscle was recorded. RESULTS: When
      neuromuscular block at the corrugator supercilii was maintained at a T1 of 10% of
      control, that at the adductor pollicis was deep (post-tetanic count <= 5).
      Sugammadex 4 mg/kg completely antagonized neuromuscular block at both muscles
      within 5 min. The time to a TOF ratio of 1.0 at the adductor pollicis was
      significantly longer in the group >= 70 years than the group 20-60 years (mean
      (SD): 178 (42.8) s vs. 120 (9.4) s, P < 0.0001). In contrast, 2 mg/kg sugammadex
      reversed neuromuscular blockade at the corrugator supercilii but not at the
      adductor pollicis, with 10 patients in the group 20-60 years and 8 patients in
      the group >= 70 years requiring an additional sugammadex (P < 0.05 vs. 4 mg/kg
      sugammadex). CONCLUSION: Sugammadex 4 mg/kg was required to reverse a moderate
      rocuronium-induced neuromuscular block when the corrugator supercilii muscle is
      used for monitoring.

PMID- 25962402
TI  - Wavelet and Gaussian Approaches for Estimation of Groundwater Variations Using
      GRACE Data.
AB  - In this study, a scheme is presented to estimate groundwater storage variations
      in Iran. The variations are estimated using 11 years of Gravity Recovery and
      Climate Experiments (GRACE) observations from period of 2003 to April 2014 in
      combination with the outputs of Global Land Data Assimilation Systems (GLDAS)
      model including soil moisture, snow water equivalent, and total canopy water
      storage. To do so, the sums of GLDAS outputs are subtracted from terrestrial
      water storage variations determined by GRACE observations. Because of stripping
      errors in the GRACE data, two methodologies based on wavelet analysis and
      Gaussian filtering are applied to refine the GRACE data. It is shown that the
      wavelet approach could better localize the desired signal and increase the signal
      to-noise ratio and thus results in more accurate estimation of groundwater
      storage variations. To validate the results of our procedure in estimation of
      ground water storage variations, they are compared with the measurements of
      pisometric wells data near the Urmia Lake which shows favorable agreements with
      our results. 

PMID- 25962401
TI  - Progression to insulin therapy among patients with type 2 diabetes treated with
      sitagliptin or sulphonylurea plus metformin dual therapy.
AB  - AIM: To assess time to insulin initiation among patients with type 2 diabetes
      mellitus (T2DM) treated with sitagliptin versus sulphonylurea as add-on to
      metformin. METHODS: This retrospective cohort study used GE Centricity electronic
      medical records and included patients aged >=18 years with continuous medical
      records and an initial prescription of sitagliptin or sulphonylurea (index date)
      with metformin for >=90 days during 2006-2013. Sitagliptin and sulphonylurea
      users were matched 1 : 1 using propensity score matching, and differences in
      insulin initiation were assessed using Kaplan-Meier curves and Cox regression. We
      used conditional logistic regression to examine the likelihood of insulin use 1-6
      years after the index date for each year. RESULTS: Propensity score matching
      produced 3864 matched pairs. Kaplan-Meier analysis showed that sitagliptin users
      had a lower risk of insulin initiation compared with sulphonylurea users (p =
      0.003), with 26.6% of sitagliptin users initiating insulin versus 34.1% of
      sulphonylurea users over 6 years. This finding remained significant after
      adjusting for baseline characteristics (hazard ratio 0.76, 95% confidence
      interval 0.65-0.90). Conditional logistic regression analyses confirmed that
      sitagliptin users were less likely to initiate insulin compared with
      sulphonylurea users [odds ratios for years 1-6: 0.77, 0.79, 0.81, 0.57, 0.29 and
      0.75, respectively (p < 0.05 for years 4 and 5)]. CONCLUSIONS: In this real-world
      matched cohort study, patients with T2DM treated with sitagliptin had a
      significantly lower risk of insulin initiation compared with patients treated
      with sulphonylurea, both as add-on to metformin.

PMID- 25962403
TI  - GLP-1-Exendin-4/IgG4 (Fc) fusion protein as a novel drug for diabetes treatment.
AB  - In this paper, we aimed to look for a potent long acting GLP-1 receptor agonist
      for diabetes treatment. In this work, we constructed the eukaryotic expression
      vector of GLP-1-Exendin-4/IgG4 (Fc)-pOptiVECTM-TOPO((r)) and then transfected it
      into Chinese hamster ovary DG44 (CHO/DG44) cells using liposome method. Then the
      beta-cell line INS-1 cells were treated with purified GLP-1-Exendin-4/IgG4 (Fc)
      fusion protein (0.01, 0.1, 1.0 mM respectively) and randomly assigned to 2
      groups, each group were then grown in KRB buffer in the presence of 2.8 mM or
      16.8 mM glucose for 2 h separately. In addition, single dose of fusion protein
      was intraperitoneally injected into male CD1 mice for pharmacokinetic study.
      Besides, multiple low doses of streptozotozin (STZ) induced diabetes mice were
      used to evaluate the effect of fusion protein for anti-diabetes in male CD1 mice.
      GLP-1-Exendin-4/IgG4 (Fc) had stimulatory effect on insulin secretion glucose
      dependently from INS-1 cells in a dose-dependent manner. Pharmacokinetic studies
      showed that the GLP-1 level increased significantly after injecting fusion
      protein and maintained a higher level for 200 h. Besides, multiple-low-dose STZ
      induced diabetes mice which received intraperitoneal injections of fusion protein
      did not show sign of diabetes. Our results indicated that GLP-1-Exendin-4/IgG4
      (Fc) fusion protein retained native GLP-1 activities and had effect on long-term
      glucose regulation. All the results suggest that this fusion protein may serve as
      a potent long acting GLP-1 receptor agonist. 

PMID- 25962404
TI  - Analysis of Heart Rate Variability and Cardiac Autonomic Nerve Remodeling in
      Streptozotocin-induced Diabetic Rats.
AB  - BACKGROUND: Diabetes mellitus (DM) is associated with both cardiovascular and
      autonomic nervous system dysfunction. Spectral analysis of heart rate variability
      (HRV) can be used to monitor changes in response to autonomic innervation and
      stimulation of the heart. In this study, conducted in a rat model of diabetes,
      HRV and changes in associated neurotransmitters and neurotrophic factors in the
      right atrium (RA) were monitored. METHODS: Diabetes was induced by streptozotocin
      (STZ) (60 mg/kg) in male Wistar rats, and HRV data were collected for 10 weeks by
      telemetry. Time and frequency domains of HRV data were analyzed using established
      metrics. The levels of various neural enzymes in the RA were determined by enzyme
      linked immunosorbent assay (ELISA) and immunofluorescence to characterize
      autonomic nerve remodeling. Insulin and methycobal were used to block the effects
      of STZ. RESULTS: HRV parameters reflecting parasympathetic tone (SDNN, RMSSD and
      HF domains) sharply decreased in the first 3 weeks after STZ administration;
      measures of sympathetic tone (SDANN) increased. After a series of adjustments,
      cardiac autonomic nerve innervation reached a new equilibrium, with a dominance
      of sympathetic tone. RA levels of tyrosine hydroxylase (TH) increased, and
      choline acetyltransferase (ChAT) decreased, indicating autonomic nerve
      remodeling. Levels of growth associated protein-43 (GAP43) and nerve growth
      factor (NGF) increased during the period of diabetes-induced cardiac-nerve
      damage; however, the level of ciliary neurotrophic factor (CNTF) decreased. The
      physical condition and indexes of rats were normalized in different degree after
      administration of the insulin and methycobal, but not completely recovered.
      CONCLUSION: STZ-induced diabetes was associated with cardiac autonomic nerve
      dysfunction at both the organ and molecular levels. Parasympathetic nerves
      exhibited severe damage and/or weak recovery; remodeling of sympathetic nerves
      predominated during 10-weeks of STZ-induced diabetes.

PMID- 25962405
TI  - Na+/Ca2+ exchanger inhibitor restores endothelium-dependent relaxation in
      diabetic rat aorta.
AB  - The aims of this study were to examine the effects of KB-R7943, an inhibitor of
      Na(+)/Ca(2+) exchanger, on the endothelium-dependent relaxation (EDR) in diabetic
      rat aorta. Both acetylcholine (ACh)-induced EDR and sodium nitroprusside (SNP)
      induced endothelium-independent relaxation (EIR) were measured in aortic rings of
      nondiabetic and streptozotocin-diabetic rats. Diabetes mellitus was induced by
      single injection of streptozotocin (60 mg/kg). The treated rats received 0.01 or
      0.1 mg/kg/day of KB-R7943 for 8 weeks. ACh-induced relaxation was impaired in
      diabetic compared to control rings and the vasodilatation to SNP was unaffected.
      Treatment with KB-R7943 markedly enhanced relaxation to ACh in diabetic but not
      in control rings. KB-R7943 significantly increased superoxide dismutase (SOD)
      activity and the nitric oxide (NO) release. These results suggest that KB-R7943
      can restore impaired EDR in aortic rings of diabetic rats, which may be related
      to scavenging oxygen free radicals and enhancing NO production. 

PMID- 25962406
TI  - An immunohistochemical investigation of the expression of somatostatin receptor
      subtypes - should therapeutic trials be performed to determine the efficacy of
      somatostatin analogs in treating advanced thyroid malignances?
AB  - Somatostatin and its analogs through the specific receptor are known to
      demonstrate antiproliferative, anti-angiogenic and pro-apoptotic actions. The
      presence of SSTR-1-5 has not been sufficiently explored in poorly differentiated
      and undifferentiated thyroid tumors. The aim was to investigate the SSTR subtypes
      expression in these aggressive thyroid tumors. The study also discusses the
      usefulness of SSTR analogs as an alternative to conventional forms of therapy.
      METHODS: The analysis was performed by immunohistochemistry on the 14 archived
      poorly differentiated and 4 anaplastic thyroid carcinomas. A group of benign
      thyroid pathologies consisting of 11 patients was also included. RESULTS: SSTR-1,
      2A, 2B, 3 and 5 were found to be expressed both in benign and malignant thyroid
      diseases, while SSTR-4 was not. Expression of SSTR-1 and SSTR-5 was found in
      samples with poorly differentiated thyroid tumors with a score of at least 2.0
      being recorded in 10 tumors (71.4%). For SSTR-2A the same or higher score was
      noted in 5/14 (35.7%), for SSTR-2B in 4/14 (28.6%) and for SSTR-3 in 3/14 (21.4%)
      samples. SSTR-1, 2B and 5 were found to have a score of at least 2.0 in all
      undifferentiated thyroid tumors. Immunostaining of SSTR-2A and 3 was observed in
      50% of samples. The immunopositive reactions were observed both in the membranes
      and cytoplasm of the thyroid cancer' cells. In some cases positive immunostaining
      was localized also in the endothelium of intrathyroidal blood vessels.
      CONCLUSIONS: The somatostatin multiligand analogs or selective agonists could be
      considered alternatives to conventional therapeutic agents in aggressive thyroid
      tumors.

PMID- 25962407
TI  - DNA methylation profiles in placenta and its association with gestational
      diabetes mellitus.
AB  - Emerging evidences indicate that placenta plays a critical role in gestational
      diabetes mellitus (GDM). DNA methylation could be associated with altered
      placental development and functions. This study is to uncover the genome-wide DNA
      methylation patterns in this disorder. DNA methylation was measured at >385,000
      CpG sites using methylated DNA immunoprecipitation (MeDIP) and a huamn CpG island
      plus promoter microarray. We totally identified 6,641 differentially methylated
      regions (DMRs) targeting 3,320 genes, of which 2,729 DMRs targeting 1,399 genes,
      showed significant hypermethylation in GDM relative to the controls, whereas
      3,912 DMRs targeting 1,970 genes showed significant hypomethylation. Functional
      analysis divided these genes into different functional networks, which mainly
      involved in the pathways of cell growth and death regulation, immune and
      inflammatory response and nervous system development. In addition, the
      methylation profiles and expressions of 4 loci (RBP4, GLUT3, Resistin and
      PPARalpha) were validated by BSP for their higher log2 ratio and potential
      functions with energy metabolism. This study demonstrates aberrant patterns of
      DNA methylation in GDM which may be involved in the pathophysiology of GDM and
      reflect the fetal development. Future work will assess the potential prognostic
      and therapeutic value for these findings in GDM.

PMID- 25962408
TI  - Problems in Interpretation of the short ACTH test: an update and historical
      notes.
AB  - ACTH stimulation test has been used for many years. Some important questions
      remain unsettled. These are reviewed and discussed in detail. Interpretation of a
      short ACTH test rests on the fact that a close correlation exists between the
      responses in plasma cortisol concentrations after administration of ACTH and
      during insulin induced hypoglycaemia which previously was the standard test. It
      is generally assumed that the plasma cortisol concentration after ACTH (and
      insulin) mirrors the response in major stress situations (surgery and critical
      disease). This notion rests on few observations. Furthermore, extensive changes
      in protein binding of cortisol occur swiftly during stress. This complicates
      comparison between cortisol responses to ACTH and to critical disease. Based on
      published studies it is discussed whether the outcome of an ACTH test is an
      appropriate indicator of the need for glucocorticosteroid replacement. This issue
      is of particular importance when deciding if permanent glucocorticosteroid
      substitution is necessary or not. 

PMID- 25962409
TI  - Hospitalisation impacts on oral hygiene: an audit of oral hygiene in a
      metropolitan health service.
AB  - BACKGROUND: Poor oral health has been associated with systemic diseases,
      morbidity and mortality. Many patients in hospital environments are physically
      compromised and rely upon awareness and assistance from health professionals for
      the maintenance or improvement of their oral health. This study aimed to identify
      whether common individual and environment factors associated with hospitalisation
      impacted on oral hygiene. METHODS: Data were collected during point prevalence
      audits of patients in the acute and rehabilitation environments on three separate
      occasions. Data included demographic information, plaque score, presence of
      dental hygiene products, independence level and whether nurse assistance was
      documented in the health record. RESULTS: Data were collected for 199 patients. A
      higher plaque score was associated with not having a toothbrush (p = 0.002),
      being male (p = 0.007), being acutely unwell (p = 0.025) and requiring nursing
      assistance for oral hygiene (p = 0.002). There was fair agreement between the
      documentation of requiring assistance for oral care and the patient independently
      able to perform oral hygiene (ICC = 0.22). CONCLUSION: Oral hygiene was impacted
      by factors arising from hospitalisation, for those without a toothbrush and male
      patients of acute wards. Establishment of practices that increase awareness and
      promote good oral health should be prioritised.

PMID- 25962410
TI  - A randomized clinical trial to evaluate the effects of rasagiline on depressive
      symptoms in non-demented Parkinson's disease patients.
AB  - BACKGROUND AND PURPOSE: Depressed mood is a common psychiatric problem associated
      with Parkinson's disease (PD), and studies have suggested a benefit of rasagiline
      treatment. METHODS: ACCORDO (see the ) was a 12-week, double-blind, placebo
      controlled trial to evaluate the effects of rasagiline 1 mg/day on depressive
      symptoms and cognition in non-demented PD patients with depressive symptoms. The
      primary efficacy variable was the change from baseline to week 12 in depressive
      symptoms measured by the Beck Depression Inventory (BDI-IA) total score.
      Secondary outcomes included change from baseline to week 12 in cognitive function
      as assessed by a comprehensive neuropsychological battery; Parkinson's disease
      quality of life questionnaire (PDQ-39) scores; Apathy Scale scores; and Unified
      Parkinson's Disease Rating Scale (UPDRS) subscores. RESULTS: One hundred and
      twenty-three patients were randomized. At week 12 there was no significant
      difference between groups for the reduction in total BDI-IA score (primary
      efficacy variable). However, analysis at week 4 did show a significant difference
      in favour of rasagiline (marginal means difference +/- SE: rasagiline -5.46 +/-
      0.73 vs. placebo -3.22 +/- 0.67; P = 0.026). There were no significant
      differences between groups on any cognitive test. Rasagiline significantly
      improved UPDRS Parts I (P = 0.03) and II (P = 0.003) scores versus placebo at
      week 12. Post hoc analyses showed the statistical superiority of rasagiline
      versus placebo in the UPDRS Part I depression item (P = 0.04) and PDQ-39 mobility
      (P = 0.007) and cognition domains (P = 0.026). CONCLUSIONS: Treatment with
      rasagiline did not have significant effects versus placebo on depressive symptoms
      or cognition in PD patients with moderate depressive symptoms. Although limited
      by lack of correction for multiple comparisons, post hoc analyses signalled some
      improvement in patient-rated cognitive and depression outcomes.

PMID- 25962411
TI  - Development of maraviroc, a CCR5 antagonist for treatment of HIV, using a novel
      tropism assay.
AB  - Assays to identify infectious organisms are critical for diagnosis and enabling
      the development of therapeutic agents. The demonstration that individuals with a
      32-bp deletion within the CCR5 locus were resistant to human immunodeficiency
      virus (HIV) infection, while those heterozygous for the mutation progressed more
      slowly, led to the discovery of maraviroc (MVC), a CCR5 antagonist. As MVC is
      only active against CCR5-tropic strains of HIV, it was critical to develop a
      diagnostic assay to identify appropriate patients. TrofileTM, a novel phenotypic
      tropism assay, was used to identify patients with CCR5-tropic virus for the MVC
      development program. Results of these clinical studies demonstrated that the
      assay correctly identified patients likely to respond to MVC. Over time, the
      performance characteristics of the phenotypic assay were enhanced, necessitating
      retesting of study samples. Genotypic tropism tests that have the potential to
      allow for local use and more rapid turnaround times are also being developed. 

PMID- 25962412
TI  - Development of influenza A(H7N9) candidate vaccine viruses with improved
      hemagglutinin antigen yield in eggs.
AB  - BACKGROUND: The emergence of avian influenza A(H7N9) virus in poultry causing
      zoonotic human infections was reported on March 31, 2013. Development of A(H7N9)
      candidate vaccine viruses (CVV) for pandemic preparedness purposes was initiated
      without delay. Candidate vaccine viruses were derived by reverse genetics using
      the internal genes of A/Puerto/Rico/8/34 (PR8). The resulting A(H7N9) CVVs needed
      improvement because they had titers and antigen yields that were suboptimal for
      vaccine manufacturing in eggs, especially in a pandemic situation. METHODS: Two
      CVVs derived by reverse genetics were serially passaged in embryonated eggs to
      improve the hemagglutinin (HA) antigen yield. The total viral protein and HA
      antigen yields of six egg-passaged CVVs were determined by the BCA assay and
      isotope dilution mass spectrometry (IDMS) analysis, respectively. CVVs were
      antigenically characterized by hemagglutination inhibition (HI) assays with
      ferret antisera. RESULTS: Improvement of total viral protein yield was observed
      for the six egg-passaged CVVs; HA quantification by IDMS indicated approximately
      a twofold increase in yield of several egg-passaged viruses as compared to that
      of the parental CVV. Several different amino acid substitutions were identified
      in the HA of all viruses after serial passage. However, HI tests indicated that
      the antigenic properties of two CVVs remained unchanged. CONCLUSIONS: If
      influenza A(H7N9) viruses were to acquire sustained human-to-human
      transmissibility, the improved HA yield of the egg-passaged CVVs generated in
      this study could expedite vaccine manufacturing for pandemic mitigation.

PMID- 25962413
TI  - Imaging Tolerance Induction in the Classic Medawar Neonatal Mouse Model: Active
      Roles of Multiple F1-Donor Cell Types.
AB  - The immature immune system is uniquely susceptible to tolerance induction and
      thus an attractive target for immunomodulation strategies for organ
      transplantation. Newborn mice injected with adult semi-allogeneic
      lymphohematopoietic cells accept transplants without immunosuppressive drugs.
      Early in vivo/in situ events leading to neonatal tolerance remain poorly
      understood. Here, we show by whole body/organ imaging that injected cells home to
      lymphoid organs and liver where various F1-donor cell types selectively alter
      neonatal immunity. In host thymus, F1-donor dendritic cells (DC) interact with
      developing thymocytes and regulatory T cells suggesting a role in negative
      selection. In spleen and lymph nodes, F1-donor regulatory T/B cells associate
      with host alloreactive cells and by themselves prolong cardiac allograft
      survival. In liver, F1-donor cells give rise to albumin-containing hepatocyte
      like cells. The neonatal immune system is lymphopenic, Th-2 immunodeviated and
      contains immature DC, suggesting susceptibility to regulation by adult F1-donor
      cells. CD8a T cell inactivation greatly enhances chimerism, suggesting that
      variable emerging neonatal alloreactivity becomes a barrier to tolerance
      induction. This comprehensive qualitative imaging study systematically shows
      contribution of multiple in vivo processes leading simultaneously to robust
      tolerance. These insights into robust tolerance induction have important
      implications for development of strategies for clinical application. 

PMID- 25962414
TI  - Primary dermal melanoma: a West Australian cohort.
AB  - BACKGROUND: The objectives of this study were to identify a subgroup of patients
      with putative primary dermal melanoma after thorough multidisciplinary clinical
      and histological evaluation, and to describe the clinical, histological and
      selected molecular features of these lesions. METHODS: The records of the Western
      Australian Melanoma Advisory Service were searched for potential cases of primary
      dermal melanoma. The clinical and histological features were reviewed,
      immunohistochemical assessment was performed and clinical outcomes recorded.
      RESULTS: Eighteen cases of putative primary dermal melanoma with available
      clinical data were identified. Two of 12 cases in which further histological
      sections could be obtained were excluded because of the presence of findings
      suggesting an epidermal origin on these further sections. In one additional case,
      such origin could not be histologically excluded. Median follow-up period for the
      remaining cases was 68 months. Confirmed primary dermal melanoma accounts for
      0.87% of cases of melanoma referred to a subspecialist melanoma advisory service.
      These cases show significant histological overlap with dermal/subcutaneous
      metastases of melanoma, but display a relatively good prognosis, with a 5-year
      survival of 87.5%. CONCLUSION: Our results support the recognition of a distinct
      group of melanoma that mimics metastatic melanoma, but is associated with a
      relatively favourable outcome. The group of putative primary dermal melanoma is
      likely to be heterogenous, including cases of primary nodular melanoma in which
      epidermal connection has not been identified, metastatic melanoma with an occult
      primary lesion and true primary dermal melanoma.

PMID- 25962415
TI  - Zoster Immunoglobulin-VF: A Potential Treatment for Molluscum Contagiosum in
      Immunosuppressed Children.
AB  - We present a brief observational report of clearance of significant molluscum
      contagiosum infection in a child taking methotrexate after one dose of
      intramuscular zoster immunoglobulin-VF (human) and suggest that this may indicate
      a potential new treatment option. 

PMID- 25962416
TI  - Multi-drug resistance and side-effects in a patient with Behcet's disease.
AB  - OBJECTIVES: To report on the clinical course of ocular and extraocular
      involvement in a multidrug-resistant patient with Behcet's disease (BD). METHODS:
      A 22-year-old male with BD (bilateral panuveitis and retinal vasculitis, oral
      ulcers, erythema nodosum, arthralgia, epididymitis) was followed-up from 1999 to
      2014. He was treated continuously with corticosteroids in combination with
      different immunosuppressive therapies (cyclosporine, azathioprine, methotrexate,
      interferon, infliximab, mycophenolate), which exerted numerous side-effects such
      as nephrotoxicity, nephrolithiasis, increase of liver enzymes, severe depression
      with suicidal ideation, severe leucopenia, pulmonary tuberculosis, pulmonary
      legionellosis, recurrent bronchopneumonia. RESULTS: Despite immunosuppressive and
      corticosteroid therapies, the patient showed multiple relapses of uveitis and
      systemic BD lesions and developed severe osteoporosis with multiple vertebral
      fractures, bilateral cataracts and steroid-associated glaucoma until 2007. Since
      then he has been treated with prednisone alone, currently at low dosage,
      remaining free from uveitis and systemic symptoms. His final visual acuity is
      9/10 in the right eye and counting fingers in the left one. CONCLUSIONS: BD
      patients are usually responsive to immunosuppressive drugs. The possibility of a
      multi-drug resistance as well as of multiple drug-related side effects cannot be
      disregarded and continuous therapy should be given in order to preserve a useful
      visual acuity until the disease, either spontaneously or drug-induced, runs into
      remission.

PMID- 25962420
TI  - [Retinal tubulation].
AB  - The aim of this study is to present a new retinal structure which is detectable
      on OCT scans - outer retinal tubulations (ORT). The discovery of these structures
      is related to more and more perfect retinal imaging using the spectral domain
      optical coherence tomography (SD OCT). Outer retinal tubulations were first
      described by Zweifel et al. in the year 2009 in patients with age-related macular
      degeneration. These branching tubular structures are localized in the outer
      nuclear layer of the retina. They are of circular or ovoid shape, with
      hyporeflectivity in the center, their borders are hyperreflective. Retinal
      tubulations are mostly seen together with choroid neovasculare membrane or with
      retinal pigment epithelium atrophy. Typically, they are adjacent to the area of
      wide damage of the outer retinal structure combined with relatively good
      preserved photoreceptor layer (respectively junctions between inner and outer
      photoreceptors segments), often they overlap the area of subretinal fibrosis or
      RPE (retinal pigment epithelium) damage. In eyes with anti-VEGF (vascular
      endothelial growth factor) treatment, they do appear in the area, where, before
      the treatment, the intraretinal fluid was present. These structures may simulate
      CME or the presence of subretinal fluid, so their determination plays an
      important role in the indications of next anti-VEGF drugs applications. Their non
      detection may cause unneeded re-applications of anti-VEGF drugs into the
      viterous. This study was presented as a lecture at the Congress of the Czech
      VitreoRetinal Society in Dolni Morava (Czech Republic, E.U.) in the year 2014.

PMID- 25962417
TI  - Characterization of repetitive DNA landscape in wheat homeologous group 4
      chromosomes.
AB  - BACKGROUND: The number and complexity of repetitive elements varies between
      species, being in general most represented in those with larger genomes.
      Combining the flow-sorted chromosome arms approach to genome analysis with second
      generation DNA sequencing technologies provides a unique opportunity to study the
      repetitive portion of each chromosome, enabling comparisons among them.
      Additionally, different sequencing approaches may produce different depth of
      insight to repeatome content and structure. In this work we analyze and
      characterize the repetitive sequences of Triticum aestivum cv. Chinese Spring
      homeologous group 4 chromosome arms, obtained through Roche 454 and Illumina
      sequencing technologies, hereinafter marked by subscripts 454 and I,
      respectively. Repetitive sequences were identified with the RepeatMasker software
      using the interspersed repeat database mips-REdat_v9.0p. The input sequences
      consisted of our 4DS454 and 4DL454 scaffolds and 4ASI, 4ALI, 4BSI, 4BLI, 4DSI and
      4DLI contigs, downloaded from the International Wheat Genome Sequencing
      Consortium (IWGSC). RESULTS: Repetitive sequences content varied from 55% to 63%
      for all chromosome arm assemblies except for 4DLI, in which the repeat content
      was 38%. Transposable elements, small RNA, satellites, simple repeats and low
      complexity sequences were analyzed. SSR frequency was found one per 24 to 27 kb
      for all chromosome assemblies except 4DLI, where it was three times higher.
      Dinucleotides and trinucleotides were the most abundant SSR repeat units.
      (GA)n/(TC)n was the most abundant SSR except for 4DLI where the most frequently
      identified SSR was (CCG/CGG)n. Retrotransposons followed by DNA transposons were
      the most highly represented sequence repeats, mainly composed of CACTA/En-Spm and
      Gypsy superfamilies, respectively. This whole chromosome sequence analysis
      allowed identification of three new LTR retrotransposon families belonging to the
      Copia superfamily, one belonging to the Gypsy superfamily and two TRIM
      retrotransposon families. Their physical distribution in wheat genome was
      analyzed by fluorescent in situ hybridization (FISH) and one of them, the Carmen
      retrotransposon, was found specific for centromeric regions of all wheat
      chromosomes. CONCLUSION: The presented work is the first deep report of wheat
      repetitive sequences analyzed at the chromosome arm level, revealing the first
      insight into the repeatome of T. aestivum chromosomes of homeologous group 4.

PMID- 25962419
TI  - Alpha-fetoprotein-producing early rectal carcinoma: a rare case report and
      review.
AB  - BACKGROUND: Alpha-fetoprotein (AFP)-producing rectal cancer is very rare, and
      this type of cancer frequently metastasizes to the liver with a poor prognosis.
      To date, only 11 cases of AFP-producing colorectal cancer have been reported.
      CASE PRESENTATION: A 41-year-old woman was first presented to the hospital for
      anal bleeding. An elevated tumor with a central shallow depression in the lower
      rectum was detected by colonoscopy. Transanal excision was performed, and the
      histology revealed adenocarcinoma. Further immunohistopathological examination
      revealed that the tumor was an AFP-producing adenocarcinoma of the rectum.
      Although local resection was performed 2 months before the diagnosis of AFP
      tumor, the serum AFP level was normal. The depth of the submucosal invasion was
      5,000 MUm, and there was venous invasion. Also, no lymphatic invasion was
      detected. Therefore, additional surgical resection with lymph node dissection was
      conducted, and the patient underwent laparoscopic intersphincteric resection. No
      residual cancer was identified in the surgical specimens, and there was no
      evidence of lymph node metastasis. The patient was discharged 18 days
      postoperatively, and 12 months after the operation, there are no signs of
      recurrence. CONCLUSION: To the best of our knowledge, this is the first case of
      an AFP-producing rectal cancer that was diagnosed at an early stage.

PMID- 25962418
TI  - Antimicrobial activity and safety evaluation of Enterococcus faecium KQ 2.6
      isolated from peacock feces.
AB  - BACKGROUND: The objective of this paper was to study antimicrobial activity and
      safety of Enterococcus faecium KQ 2.6 (E. faecium KQ 2.6) isolated from peacock
      feces. METHODS: Agar well diffusion method was adopted in antimicrobial activity
      assay. Disk diffusion test was used to determine the antibiotic resistance. The
      identification and virulence potential of E. faecium KQ 2.6 were investigated
      using PCR amplification. RESULTS: The results indicated that cell free
      supernatant (CFS) of the strain had the good antimicrobial activity against
      selected gram-positive and gram-negative bacteria. The biochemical
      characteristics of antimicrobial substances were investigated. The results
      indicated that the antimicrobial substances were still active after treatment
      with catalase and proteinase, respectively. Moreover, the stability of
      antimicrobial substances did not change after heat treatment at 40, 50, 60, 70
      and 80 degrees C for 30 min, respectively. The activity of antimicrobial
      substances remained stable at 4 and -20 degrees C after long time storage. The
      antimicrobial activity of CFS was compared with that of the buffer with similar
      strength and pH. The inhibitory zone of the buffer was apparently smaller than
      that of CFS, which meant that the acid in CFS was not the only factor that was
      contributed to antibacterial activity of CFS. The antibiotic resistance and
      virulence potential were evaluated using disk diffusion test and PCR
      amplification. The results showed that E. faecium KQ 2.6 did not harbor any
      tested virulence genes such as gelE, esp, asa1, cylA, efaA and hyl. It was
      susceptible to most of tested antibiotics except for vancomycin and polymyxin B.
      CONCLUSION: E. faecium KQ 2.6 may be used as bio-preservative cultures for the
      production of fermented foods.

PMID- 25962421
TI  - [Clinical Results after Continuous Corneal ring (MyoRing) Implantation in
      Keratoconus Patients].
AB  - PURPOSE: to present one and two years clinical results after intrastromal
      continuous corneal ring implantation in keratoconus patients. METHODS:
      Retrospective evaluation of the results of patients with keratoconus, after
      MyoRing implantation for improving of visual functions. The uncorrected distance
      visual acuity (UDVA), best corrected distance visual acuity (CDVA), the residual
      subjective refractive error, pachymetry, keratometry and the size of corneal
      astigmatismus were evaluated. Peroperative and postoperative complications were
      investigated. The minimal follow-up time was 12 months. RESULTS: The study
      included 32 eyes of 30 patients with mean age of 30.08 (+/- 11.56) years. UDVA
      improved from 1.03 (+/- 0.41) logMAR to 0.36 (+/- 0.25) logMAR 12 months and 0.31
      (+/- 0.27) logMAR 24 months after surgery. These changes were stastistically
      significant. The maxima value of corneal curvature (Kmax) was preoperatively
      52.48 (+/- 6.35) D, 46.08 (+/- 4.44) D 12 months and 45.53 (+/- 5.52) D 24 months
      after surgery. Both changes were statistically significant (P ? 0,00000). The
      mean value of corneal curvature (K mean) was preoperatively 50.10 (+/- 4.96) D,
      44.25 (+/- 4.40) D 12 months and 44.11 (+/- 5.38) D 24 months after surgery. Both
      changes were statistically significant. In any of the patients we did not
      register any severe peroperative or postoperative complication. CONCLUSION: The
      MyoRing implantation is an effective and safe method in improvement of visual
      functions in keratoconus patients. Clinical results are stable in one and two
      years follow-up time.

PMID- 25962422
TI  - [The Changes of the Spectrum in Primarily Indicated Surgeries due to Retinal
      Detachment during the Period of 15 Years].
AB  - PURPOSE: To evaluate the effectiveness of surgery for the rhegmatogenous retinal
      detachment, depending upon changes in the type of the primary surgery in the last
      15 years. MATERIALS AND METHODS: There were 991 patients with primary
      rhegmatogenous retinal detachment operated (in total 1020 eyes) at the Department
      of Ophthalmology Faculty of Medicine and University Hospital Bratislava. In the
      prospective part, in A group concerning the years 1999-2001, there were 346 eyes,
      339 patients included. In the first retrospective part, in B group concerning the
      years 1994-1998 there were 464 eyes, 455 patients. In the second retrospective
      part, in C group concerning the years 2009-2010, 210 eyes, 197 patients were
      enrolled. We have analyzed the anatomical and functional results, focusing on the
      primary indicated surgical procedure of retinal detachment. The primary pars
      plana vitrectomy was in A group indicated in 54,6%, in group B in 27,6% and in
      group C in 90,4%. RESULTS: We have recorded the improvement of visual acuity
      after retinal detachment surgery in A group in 54.7% of eyes, in B group in 58.2%
      of eyes and in C group in 57% of eyes. The same visual acuity as it was before
      the first surgery for retinal detachment was recorded in A group in 26.8%, in B
      group in 19.8% and in C group C in 28% of eyes. Attached retina has been achieved
      in 75 % in A group after the first surgery and after the last surgical procedure
      the success rate increased to 98%. The anatomical success was 72% of eyes after
      the first surgery in B group and after the last surgery it was 94%, in C group
      the retina was attached in the 74% after primary surgery and 99% after the last
      surgery. CONCLUSION: The changing of spectrum indicated by primary retinal
      detachment surgeries for the last 15 years has not brought the expected major
      functional and anatomical improvement.

PMID- 25962423
TI  - [Aflibercept in clinical practice].
AB  - In this article we have tried to evaluate first clinical experience with the
      effectiveness and safety of aflibercept in the treatment of the wet form of age
      related macular degeneration in all types of subretinal neovascular membranes for
      the period of the first 10 months of treatment in our clinic.

PMID- 25962424
TI  - [Acute zonal occult outer retinopathy - a case with rapid return of visual
      functions in type 3 disease].
AB  - Acute zonal occult outer retinopathy is noninfectious zonal dysfunction of outer
      retina often adjacent to optic nerve. It is accompanied by temporary
      disappearance of retinal fotoreceptor layer, visual acuity drop and late
      pigmentary fundus changes. Authors present a case report of a patient with
      unilateral involvement and spontaneous visual acuity resolution followed by quick
      reappearance of photoreceptor layer on OCT.

PMID- 25962425
TI  - [STORY of the Papilla - a Case Report].
AB  - PURPOSE: To present a case report with "unclear" and sudden decrease of left eye
      visual acuity and bilateral visual fields defects. METHODS: A case report. CASE
      PRESENTATION: A 66-year-old woman was referred to our Center of
      Neuroophthalmology and Orbitology by a neurologist for a history of sudden
      decrease of visual acuity of her left eye 3 years ago. From September 2009, she
      was examined at various and not only ophthalmology departments. One by one the
      optic nerve neuritis, traumatic, compressive or toxic neuropathy and also
      nutritive neuropathy because of vitamin B(12) deficiency were excluded. The
      patient underwent also a genetic examination for Lebers hereditary optic nerve
      neuropathy, but this diagnosis was not confirmed. On magnetic resonance imaging,
      an atrophy of both optic nerves was described, with no further progression found
      during the follow-up examination after one year. In available patients medical
      records we found out that on optical coherence tomography scans optic disc drusen
      of the both eyes are visible, but this wasnt described in the records. Also, an
      examination of Visual Evoked Potential was performed - this confirmed the
      diagnosis of optic disc drusen. However, our patient was further examined for
      visual lost of the left eye. At the time of presentation (January, 2014), her
      best-corrected visual acuity of the right eye was 0.5, and counting fingers at 50
      cm distance with correct light projection in the left eye. Static perimetric
      examination demonstrated bilateral and concentric narrowing of visual fields. The
      eyes were parallel, with no limitation of their movements in any direction. The
      patient was without diplopia, the direct pupil reactions to the light were
      sluggish bilaterally, and anterior segments of both eyes were with no
      pathologies. Examination of the fundus revealed bilateral findings of pale optic
      disc with absent optic cup and indistinct "lumpy" margins. Waxy pearl-like
      irregularities of the papila of both eyes were visible even without pupil
      dilatation. Bilateral optic disc drusen were confirmed by ultrasonography, fundus
      autofluorescence and spectral-domain optical coherence tomography. CONCLUSION:
      Optic disc drusen are often asymptomatic, frequently it is an accidental finding
      during the biomicroscopy of fundus due to ordinary eye examination. Rarely, optic
      disc drusen can cause blood circulation failure on the optic disc with typical
      defects of the visual field. Thats why we shouldnt forget the optic disc drusen
      in the differential diagnosis considerations.

PMID- 25962426
TI  - Phase I/II study of temsirolimus for patients with unresectable Hepatocellular
      Carcinoma (HCC)- a correlative study to explore potential biomarkers for
      response.
AB  - BACKGROUND: The oncogenic PI3K/Akt/mTOR pathway is frequently activated in HCC.
      Data on the mTOR inhibitor, temsirolimus, is limited in HCC patients with
      concomitant chronic liver disease. The objectives of this study were: (1) In
      phase I, to determine DLTs and MTD of temsirolimus in HCC patients with chronic
      liver disease; (2) In phase II, to assess activity of temsirolimus in HCC, and
      (3) to explore potential biomarkers for response. METHODS: Major eligibility
      criteria included histologically confirmed advanced HCC and adequate organ
      function. In Phase I part of the study, temsirolimus was given weekly in 3-weekly
      cycle; dose levels were 20 mg (level 1), 25 mg (level 2) and 30 mg (level 3). The
      MTD was used in the subsequent phase II part; the primary endpoint was PFS and
      secondary endpoints were response and OS. In addition, exploratory analysis was
      conducted on pre-treatment tumour tissues to determine stathmin, pS6, pMTOR or p
      AKT expressions as potential biomarkers for response. Overall survival and PFS
      were calculated using the Kaplan-Meier method. Reassessment CT scans were done
      every 6 weeks. All adverse events were reported using CTCAE v3. RESULTS: The
      Phase I part consisted of 19 patients, 2 of 6 patients at level 3 experienced
      DLT; dose level 2 was determined to be the MTD. The phase II part consisted of 36
      patients. Amongst 35 assessable patients, there were 1 PR, 20 SD and 14 PD.
      Overall, the median PFS was 2.83 months (95% C.I. 1.63-5.24). The median OS was
      8.89 months (95% C.I. 5.89-13.30). Grade >= 3 that occurred in > 10% of patients
      included thrombocytopenia (4) and hyponatraemia (4). Exploratory analysis
      revealed that disease stabilization (defined as CR + PR + SD > 12 weeks) in
      tumours having high and low pMTOR H-scores to be 70% and 29% respectively (OR
      5.667, 95% CI 1.129-28.454, p = 0.035). CONCLUSIONS: In HCC patients with chronic
      liver disease, the MTD of temsirolimus was 25 mg weekly in a 3-week cycle. The
      targeted PFS endpoint was not reached. However, further studies to identify
      appropriate patient subgroup are warranted. TRIAL REGISTRATION: This study has
      been registered in ClinicalTrials.gov (Id: NCT00321594) on 1 December 2010.

PMID- 25962427
TI  - Absence of toll-like receptor 4 (TLR4) extends survival in the hSOD1 G93A mouse
      model of amyotrophic lateral sclerosis.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating late onset
      neurodegenerative disorder that is characterised by the progressive loss of upper
      and lower motor neurons. The mechanisms underlying ALS pathogenesis are unclear;
      however, there is emerging evidence the innate immune system, including
      components of the toll-like receptor (TLR) system, may drive disease progression.
      For example, toll-like receptor 4 (TLR4) antagonism in a spontaneous 'wobbler
      mouse' model of ALS increased motor function, associated with a decrease in
      microglial activation. This study therefore aimed to extend from these findings
      and determine the expression and function of TLR4 signalling in hSOD1(G93A) mice,
      the most widely established preclinical model of ALS. FINDINGS: TLR4 and one of
      its major endogenous ligands, high-mobility group box 1 (HMGB1), were increased
      during disease progression in hSOD1(G93A) mice, with TLR4 and HMGB1 expressed by
      activated microglia and astrocytes. hSOD1(G93A) mice lacking TLR4 showed
      transient improvements in hind-limb grip strength and significantly extended
      survival when compared to TLR4-sufficient hSOD1(G93A) mice. CONCLUSION: These
      results suggest that enhanced glial TLR4 signalling during disease progression
      contributes to end-stage ALS pathology in hSOD1(G93A) mice.

PMID- 25962428
TI  - Erythrocyte membrane-coated NIR-triggered biomimetic nanovectors with programmed
      delivery for photodynamic therapy of cancer.
AB  - A new type of photodynamic therapy (PDT) agents using upconversion nanoparticles
      (UCNPs) with incorporated photosensitizers as the inner core and an erythrocyte
      membrane (RM) decorated with dual targeting moieties as the cloak is developed.
      Owing to the endogenous nature of RM, the RM-coating endows the PDT agents with
      perfect biocompatibility and stealth ability to escape from the entrapment by the
      reticulo-endothelial system (RES). More importantly, owing to the unique nature
      of erythrocyte as an oxygen carrier in the blood, the RM outer layer of the
      agents unequivocally facilitates the permeation of ground-state molecular oxygen
      ((3)O2) and the singlet oxygen ((1)O2) as compared to the previously developed
      PDT agents with other types of coating. Another salient feature of the as
      prepared PDT platform is the decoration of RM with dual targeting moieties for
      selective recognition of cancer cells and mitochondrial targeting, respectively.
      The synergistic effect of RM coating and dual-targeting of such feature-packed
      agents are investigated in tumor-bearing mice and the improved PDT therapeutic
      efficacy is confirmed, which is the first paradigm where RM-coated NIR-triggered
      nanovectors with programmed delivery ability is applied in PDT of tumor in vivo. 

PMID- 25962429
TI  - FOXM1-mediated downregulation of uPA and MMP9 by 3,3'-diindolylmethane inhibits
      migration and invasion of human colorectal cancer cells.
AB  - Although 3,3'-diindolylmethane (DIM) has been suggested to reduce the risk of
      colorectal cancer, the underlying biological mechanism is not clearly understood.
      In the present study, we investigated the effect of DIM on the migratory and
      invasive activities of the human colorectal cancer cell lines DLD-1 and HCT116.
      DIM significantly inhibited the migration and invasion of colorectal cancer cells
      as assessed by wound healing and Matrigel invasion assays. The migratory ability
      of the DLD-1 and HCT116 cells was significantly reduced by DIM at 24 and 48 h.
      DIM also significantly inhibited the invasion rate of the DLD-1 and HCT116 cells
      in a dose-dependent manner. The mRNA expression levels of urokinase type
      plasminogen activator (uPA) and matrix metalloprotease 9 (MMP9) were
      significantly attenuated, whereas expression of E-cadherin mRNA was significantly
      enhanced, following DIM treatment. DIM also decreased the protein levels of uPA
      and MMP9, yet significantly increased E-cadherin protein expression. In addition,
      DIM significantly reduced the mRNA and protein levels of FOXM1 in the DLD-1 and
      HCT116 cells. Our results suggest that DIM can influence the cell migratory and
      invasive properties of human colorectal cancer cells and may decrease the
      invasive capacity of colorectal cancer through downregulation of uPA and MMP9
      mediated by suppression of the transcription factor FOXM1.

PMID- 25962430
TI  - Identification of microRNAome in rat bladder reveals miR-1949 as a potential
      inducer of bladder cancer following spinal cord injury.
AB  - The costs of spinal cord injury and its complications are high in personal,
      social and financial terms. Complications include bladder cancer, for which the
      risk is 16-28 times higher than that of the general population, There is
      currently little consensus regarding the cause of this discrepancy. As microRNAs
      are stable biomarkers and potential therapeutic targets of cancer, the present
      study aimed to explore the underlying mechanisms of this phenomenon by examining
      changes in the microRNAome. Rats were used to produce models of spinal cord
      injury. Microarrays and bioinformatics were used to investigate the cancer
      associated microRNAs that are upregulated in rat bladders following spinal cord
      injury. In order to validate the results, quantitative reverse transcription
      polymerase chain reaction (qRT-PCR), western blotting and immunohistochemistry
      were performed. The expression of miR-1949 was found to be deregulated and
      abundant in the rat bladder following spinal cord injury. Bioinformatics
      demonstrated that retinoblastoma 1, which is involved in tumorigenesis, is a
      target gene of miR-1949. qRT-PCR, western blotting and immunohistochemistry
      confirmed the results of the microarray analysis. In addition, it was shown that
      miR-1949 expression was not influenced by aging. Furthermore, the expression of
      miR-1949 was stable until the third month following spinal cord injury, after
      which it significantly increased. If this increase was prolonged, the expression
      of retinoblastoma 1 may decline to a carcinogenic level. The present study
      suggests a role for miR-1949 in the translational regulation of retinoblastoma 1
      and in subsequent bladder tumorigenesis following spinal cord injury.

PMID- 25962432
TI  - Supported catalysts based on layered double hydroxides for catalytic oxidation
      and hydrogenation: general functionality and promising application prospects.
AB  - Oxidation and hydrogenation catalysis plays a crucial role in the current
      chemical industry for the production of key chemicals and intermediates. Because
      of their easy separation and recyclability, supported catalysts are widely used
      in these two processes. Layered double hydroxides (LDHs) with the advantages of
      unique structure, composition diversity, high stability, ease of preparation and
      low cost have shown great potential in the design and synthesis of novel
      supported catalysts. This review summarizes the recent progress in supported
      catalysts by using LDHs as supports/precursors for catalytic oxidation and
      hydrogenation. Particularly, partial hydrogenation of acetylene, hydrogenation of
      dimethyl terephthalate, methanation, epoxidation of olefins, elimination of NOx
      and SOx emissions, and selective oxidation of biomass have been chosen as
      representative reactions in the petrochemical, fine chemicals, environmental
      protection and clean energy fields to highlight the potential application and the
      general functionality of LDH-based catalysts in catalytic oxidation and
      hydrogenation. Finally, we concisely discuss some of the scientific challenges
      and opportunities of supported catalysts based on LDH materials. 

PMID- 25962431
TI  - Association of the Asp312Asn and Lys751Gln polymorphisms in the XPD gene with the
      risk of non-Hodgkin's lymphoma: evidence from a meta-analysis.
AB  - Polymorphisms in DNA repair genes may alter DNA repair capacity and,
      consequently, lead to genetic instability and carcinogenesis. Several studies
      have investigated the association of the Asp312Asn and Lys751Gln polymorphisms in
      the xeroderma pigmentosum complementation group D (XPD) gene with the risk of non
      Hodgkin's lymphoma (NHL), but the conclusions have been inconsistent. Therefore,
      we performed this meta-analysis to more precisely estimate these relationships. A
      systematic literature search was performed using the PubMed, Embase, and Chinese
      Biomedical (CBM) databases. Ultimately, 6 studies of Asp312Asn, comprising 3,095
      cases and 3,306 controls, and 7 studies of Lys751Gln, consisting of 3,249 cases
      and 3,676 controls, were included. Pooled odds ratios (ORs) and 95% confidence
      intervals (CIs) were calculated to assess the strength of each association.
      Overall, no association was observed between the Asp312Asn polymorphism and NHL
      risk (homozygous: OR = 1.11, 95% CI = 0.94-1.32; heterozygous: OR = 1.00, 95% CI
      = 0.89-1.11; recessive: OR = 1.12, 95% CI = 0.95-1.31; dominant: OR = 1.02, 95%
      CI = 0.92-1.13; and allele comparison: OR = 1.04, 95% CI = 0.96-1.12) or between
      the Lys751Gln polymorphism and NHL risk (homozygous: OR = 0.97, 95% CI = 0.83
      1.15; heterozygous: OR = 0.96, 95% CI = 0.86-1.06; recessive: OR = 1.00, 95% CI =
      0.86-1.16; dominant: OR = 0.96, 95% CI = 0.87-1.06; and allele comparison: OR =
      0.98, 95% CI = 0.91-1.05). Furthermore, subgroup analyses did not reveal any
      association between these polymorphisms and ethnicity, the source of the
      controls, or the NHL subtype. These results indicated that neither the Asp312Asn
      nor Lys751Gln XPD polymorphism was related to NHL risk. Large and well-designed
      prospective studies are required to confirm this finding. 

PMID- 25962433
TI  - Magnesium-induced recurarisation after reversal of rocuronium-induced
      neuromuscular block with sugammadex. Findings vs. speculation.

PMID- 25962434
TI  - Gout, anxiety, and depression in primary care: a matched retrospective cohort
      study.

PMID- 25962435
TI  - Chronic myeloid leukemia with e14a3 BCR-ABL transcript: analysis of
      characteristics and prognostic significance.
AB  - Chronic myeloid leukemia (CML) is characterized by Philadelphia chromosome (Ph)
      and BCR-ABL fusion genes. This study retrospectively analyzed 2381 CML patients
      with Ph chromosome confirmed by cytogenetics, Fluorescence in situ hybridization
      (FISH) or real-time quantitative polymerase chain reaction (Q-PCR). Among them,
      five CML patients without e13a2, e14a2 or e1a2 transcripts detected by Q-PCR were
      identified. DNA sequencing confirmed the fusion of BCR exon 14 and ABL exon 3.
      Case 1 reponded poorly to imatinib and achieved complete cytogenetic response
      (CCyR) after converting from imatinib to dasatinib. BCR-ABL transcripts were
      undetectable in cases after 2, 3 and 4 treated with imatinib after 6, 6 and 3
      months, respectively, and in one patient who had undergone allogeneic
      hematopoietic stem cell transplantation after 4 months. Q-PCR may miss the
      detection of rare cases that are not covered by the primers used in Q-PCR, unless
      the proper primers are used. 

PMID- 25962436
TI  - Long-term complete remission by infusion of ex vivo-expanded donor-derived CD4(+)
      lymphocytes for treating an early relapse of Hodgkin lymphoma after cord blood
      transplantation.

PMID- 25962437
TI  - Immobilised molecular catalysts and the role of the supporting metal substrate.
AB  - This work demonstrates that immobilising molecular catalysts on metal substrates
      can attenuate their reactivity. In particular, the reactivity towards molecular
      oxygen of both ruthenium tetraphenyl porphyrin (Ru-TPP) and its Ti analogue (Ti
      TPP) on Ag(111) was studied as benchmark for the interaction strength of such
      metal-organic complexes with possible reactants. Here, Ru-TPP proves to be
      completely unreactive and Ti-TPP strongly reactive towards molecular oxygen;
      along with comparison to work in the literature, this suggests that studies into
      immobilised catalysts might find fruition in considering species traditionally
      seen as too strongly interacting. 

PMID- 25962438
TI  - Chronic relapsing remitting Sweet syndrome--a harbinger of myelodysplastic
      syndrome.
AB  - Sweet syndrome (SS) is an acute febrile neutrophilic dermatosis. It has been
      associated with malignant disease, especially acute myeloid leukaemia (AML),
      infections, autoimmune disorders and drugs, particularly granulocyte colony
      stimulating factor (GCSF). No cause is found in the rest, which are labelled
      idiopathic. We describe 15 patients with SS, which we believe represent 'immune
      dysregulation' secondary to myelodysplastic syndrome (MDS). We initially
      identified 31 patients with SS in a cohort of 744 patients with MDS and 215 with
      AML seen over a 6-year period (2004-10). The cause in 16 patients could be
      attributed either to administration of GCSF or chemotherapy. The eruption was
      brief and resolved spontaneously or following withdrawal of GCSF. Fifteen
      patients however, had a chronic debilitating illness dominated by the skin
      eruptions. Diagnosis of chronic relapsing SS was delayed because the pathology
      was not always typical of classical neutrophil-rich SS and included lymphocytic
      and histiocytoid infiltrates and bone marrow was not always performed because the
      relevance of the eruption to MDS was often not immediately appreciated. All these
      patients had 'low risk' MDS, diagnosed at a median of 17 months (range 0-157)
      following the diagnosis of SS. We describe a chronic debilitating episodic
      clinically distinctive skin eruption with features of SS but not always
      definitive histopathology often associated with immunological abnormalities
      affecting other systems related to underlying low risk MDS. 

PMID- 25962441
TI  - 'Industry corner: perspectives and controversies': a new series in Annals of
      Oncology.

PMID- 25962439
TI  - In vivo efficacy of sulphadoxine-pyrimethamine for the treatment of asymptomatic
      parasitaemia in pregnant women in Machinga District, Malawi.
AB  - BACKGROUND: The effectiveness of sulphadoxine-pyrimethamine (SP) intermittent
      preventive treatment of malaria in pregnancy (IPTp) might be compromised by high
      prevalence of resistance-associated Plasmodium falciparum dihydrofolate reductase
      (dhfr) and dihydropteroate synthase (dhps) mutations. As a proxy for IPTp-SP
      effectiveness, the in vivo efficacy of SP to clear parasitaemia and prevent
      reinfection in asymptomatic parasitaemic pregnant women in an area with high SP
      resistance prevalence was assessed. METHODS: Pregnant women 16-26 weeks'
      gestation with asymptomatic parasitaemia presenting for antenatal care were given
      IPTp-SP and followed for 42 days. The primary outcome was polymerase chain
      reaction (PCR) uncorrected 42-day survival rate; the per cent of patients without
      recrudescence or reinfection by day 42. PCR was used to distinguish recrudescence
      from reinfection. DNA was sequenced to detect resistance-associated dhfr and dhps
      mutations. RESULTS: Of 245 pregnant women included in the intention-to-treat
      analysis, 93.9% cleared their parasitaemia by day 7. The day 42 PCR-uncorrected
      survival rate was 58.1% (95% confidence interval (CI) 51.5-65.7) and day 42 PCR
      corrected survival was 68.7% (CI 61.4-76.0). Recrudescence was more common among
      primi- than among multigravid women; recrudescence rate 33.3% (CI 25.1-42.4%)
      versus 21.4% (CI 15.0-29.0%) (log rank test p-value 0.006). The quintuple mutant
      was present in nearly all samples (95%), while 2% were sextuple mutants with an
      additional mutation at dhps A581G. CONCLUSIONS: SP efficacy for acute malaria
      treatment has been compromised by resistance, but SP retains partial activity
      among pregnant women with asymptomatic parasitaemia, and thus might be useful for
      IPTp. Nonetheless, research on non-SP IPTp regimens should continue. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01120145 .

PMID- 25962440
TI  - Clinical usefulness of PI3K/Akt/mTOR genotyping in companion with other clinical
      variables in metastatic renal cell carcinoma patients treated with everolimus in
      the second and subsequent lines.
AB  - BACKGROUND: The aim of this study was to search for predictive and prognostic
      factors in patients with metastatic renal cell carcinoma (mRCC) treated with
      everolimus among the components of PI3K/AKT/mTOR pathway. PATIENTS AND METHODS:
      In a prospective, one-arm, phase II study, patients with mRCC received everolimus
      (10 mg/day) using a 30-day cycle. A prospectively planned evaluation of potential
      biomarkers of PI3K/AKT/mTOR pathway. RESULTS: The median age of the 58 patients
      enrolled into the study was 60 years (range 41-78 years). In multivariate
      analysis, it was found that the adverse independent predictors for everolimus
      therapy were histological grade G1/2 {hazard ratio (HR): 2.68 [95% confidence
      interval (CI) 1.29-5.58, P = 0.0082]}, increased lactate dehydrogenase (LDH)
      level before treatment [HR: 2.55 (95% CI 1.30-4.99, P = 0.0064)] and the PIK3CA
      gene variant rs6443624 (HR: AC + AA versus CC = 2.08, 95% CI 1 11-3.89, P =
      0.0254). In multivariate analysis, it was observed that the adverse independent
      prognostic factors were: elevated corrected calcium level [HR: 4.17 (95% CI 1.66
      10.51; P = 0.0024)] and the PIK3CA gene variant rs6443624 [HR: AC + AA versus CC
      = 1.97 (95% CI 1.02-3.79; P = 0.0421)]. CONCLUSIONS: The PI3KCA gene
      polymorphism, LDH, and histologic grade can predict the effects of everolimus
      treatment. The corrected calcium level and the PIK3CA gene variant rs6443624 may
      be independent prognostic factors. Further investigation is needed to confirm and
      validate these findings prospectively in other RCC trials.

PMID- 25962442
TI  - Long-term ovarian function in women treated with CHOP or CHOP plus etoposide for
      aggressive lymphoma.
AB  - BACKGROUND: Chemotherapy-associated ovarian damage comprises not only
      infertility, but also premature menopause. The latter has been reported as a
      consequence of alkylating chemotherapy for breast cancer or Hodgkin's lymphoma.
      In this study, we assessed the long-term impact of CHOP (cyclophosphamide,
      doxorubicin, vincristine, and prednisone)-like regimens on ovarian function in
      patients with aggressive non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS: Long
      term survivors after CHOP or CHOP plus etoposide (CHOEP) treatment within the
      Mabthera International Trial or the NHL-B1 trial of the German NHL Study Group
      were requested to respond to a questionnaire and to consent to blood sampling for
      hormone assessment. RESULTS: A total of 46 of 81 contacted patients with a median
      age of 32.5 years at the time of enrolment into the aforementioned clinical
      trials responded to the questionnaire. The median follow-up after completion of
      treatment was 14 years. Last menstrual bleeding occurred significantly earlier in
      patients compared with the general population (47 versus 51 years, P < 0.0001).
      In comparison to the distribution of menopausal symptoms in the general
      population, the percentage of women with moderate or severe menopausal symptoms
      was increased. In 23 patients who agreed to participate in laboratory analyses,
      anti-Muller hormone as a marker of ovarian reserve was decreased when compared
      with correspondent age groups of the general population. CONCLUSION: Although
      most female patients regain fertility after CHOP-like chemotherapy, late ovarian
      impairment occurs frequently. Therefore, awareness of such delayed side-effects
      at the time of counselling is of importance.

PMID- 25962443
TI  - Multi-Cereal Beverage Fermented by Lactobacillus Helveticus and Saccharomyces
      Cerevisiae.
AB  - A novel multi-cereal-based fermented beverage with suitable aroma, flavor, and pH
      fermented by lactic acid bacteria and Saccharomyces cerevisiae was developed.
      Twenty-seven lactobacilli strains were screened for acid production (pH and
      titratable acidity) in a mixture of malt, rice, and maize substrates. It was
      found that Lactobacillus helveticus KLDS1.9204 had the greatest acid production
      among 27 lactobacilli tested. The fermentation performance of L. helveticus
      KLDS1.9204 was also assayed and the fermentation parameters were optimized using
      Plackett-Burman design and steepest ascent method. L. helveticus KLDS1.9204
      showed good proteolytic capability, however, the strain could not utilize starch.
      The optimum substrate consisted of 50% malt (25 g/100 mL), 25% rice (20 g/100
      mL), and 25% maize (30 g/100 mL). The inoculum was 5% with a ratio of S.
      cerevisiae to L. helveticus KLDS1.9204 of 2.5:1. The optimum temperature was 37 
      degrees C and the time was 22 h. Lastly, the quality of the multi-cereal-based
      fermented beverage was evaluated. This beverage was light yellow, transparent,
      and it tasted well with a pleasant acid and a unique flavor of cereals. The
      beverage was rich in free amino acids and organic acids. The pH and titratable
      acidity of the beverage were 3.5 and 29.86  degrees T, respectively. The soluble
      solids content of the beverage was 6.5  degrees Brix, and the alcohol content was
      0.67%. 

PMID- 25962444
TI  - A holistic comparative analysis of diagnostic tests for urothelial carcinoma: a
      study of Cxbladder Detect, UroVysion(r) FISH, NMP22(r) and cytology based on
      imputation of multiple datasets.
AB  - BACKGROUND: Comparing the relative utility of diagnostic tests is challenging
      when available datasets are small, partial or incomplete. The analytical leverage
      associated with a large sample size can be gained by integrating several small
      datasets to enable effective and accurate across-dataset comparisons.
      Accordingly, we propose a methodology for a holistic comparative analysis and
      ranking of cancer diagnostic tests through dataset integration and imputation of
      missing values, using urothelial carcinoma (UC) as a case study. METHODS: Five
      datasets comprising samples from 939 subjects, including 89 with UC, where up to
      four diagnostic tests (cytology, NMP22(r), UroVysion(r) Fluorescence In-Situ
      Hybridization (FISH) and Cxbladder Detect) were integrated into a single dataset
      containing all measured records and missing values. The tests were firstly ranked
      using three criteria: sensitivity, specificity and a standard variable (feature)
      ranking method popularly known as signal-to-noise ratio (SNR) index derived from
      the mean values for all subjects clinically known to have UC versus healthy
      subjects. Secondly, step-wise unsupervised and supervised imputation (the latter
      accounting for the 'clinical truth' as determined by cystoscopy) was performed
      using personalized modelling, k-nearest-neighbour methods, multiple logistic
      regression and multilayer perceptron neural networks. All imputation models were
      cross-validated by comparing their post-imputation predictive accuracy for UC
      with their pre-imputation accuracy. Finally, the post-imputation tests were re
      ranked using the same three criteria. RESULTS: In both measured and imputed data
      sets, Cxbladder Detect ranked higher for sensitivity, and urine cytology a higher
      specificity, when compared with other UC tests. Cxbladder Detect consistently
      ranked higher than FISH and all other tests when SNR analyses were performed on
      measured, unsupervised and supervised imputed datasets. Supervised imputation
      resulted in a smaller cross-validation error. Cxbladder Detect was robust to
      imputation showing a 2% difference in its predictive versus clinical accuracy,
      outperforming FISH, NMP22 and cytology. CONCLUSION: All data analysed, pre- and
      post-imputation showed that Cxbladder Detect had higher SNR and outperformed all
      other comparator tests, including FISH. The methodology developed and validated
      for comparative ranking of the diagnostic tests for detecting UC, may be further
      applied to other cancer diagnostic datasets across population groups and multiple
      datasets.

PMID- 25962445
TI  - Prenatal ultrasound and postmortem histologic evaluation of tooth germs: an
      observational, transversal study.
AB  - INTRODUCTION: Hypodontia is the most frequent developmental anomaly of the
      orofacial complex, and its detection in prenatal ultrasound may indicate the
      presence of congenital malformations, genetic syndromes and chromosomal
      abnormalities. To date, only a few studies have evaluated the histological
      relationship of human tooth germs identified by two-dimensional (2D)
      ultrasonography. In order to analyze whether two-dimensional ultrasonography of
      tooth germs may be successfully used for identifying genetic syndromes, prenatal
      ultrasound images of fetal tooth germs obtained from a Portuguese population
      sample were compared with histological images obtained from fetal autopsies.
      METHODS: Observational, descriptive, transversal study. The study protocol
      followed the ethical principles outlined by the Helsinki Declaration and was
      approved by the Ethics Committee of the School of Dental Medicine, University of
      Porto (FMDUP, Porto, Portugal) and of the Centro Hospitalar de Vila Nova de
      Gaia/Espinho (CHVNG/EPE, Porto, Portugal) as well as by the CGC Genetics
      Embryofetal Pathology Laboratory. Eighty-five fetuses examined by prenatal
      ultrasound screening from May 2011 to August 2012 had an indication for autopsy
      following spontaneous fetal death or medical termination of pregnancy. Of the 85
      fetuses, 37 (43.5%) were randomly selected for tooth germ evaluation by routine
      histopathological analysis. Fetuses who were up to 30 weeks of gestation, and
      whose histological pieces were not representative of all maxillary tooth germs
      was excluded. Twenty four fetus between the 13(th) and 30(th) weeks of gestation
      fulfilled the parameters to autopsy. RESULTS: Twenty four fetuses were submitted
      to histological evaluation and were determined the exact number, morphology, and
      mineralization of their tooth germs. All tooth germs were identifiable with
      ultrasonography as early as the 13(th) week of gestation. Of the fetuses
      autopsied, 41.7% had hypodontia (29.1% maxillary hypodontia and 20.9% mandibular
      hypodontia). CONCLUSIONS: This results indicate that prenatal ultrasound is a
      reliable method for detecting of hypodontia an early gestational ages. Further
      studies with larger samples are needed to confirm these results.

PMID- 25962446
TI  - Views of early psychosis clinicians on discontinuation of antipsychotic
      medication following symptom remission in first episode psychosis.
AB  - AIMS: Discontinuation of antipsychotics following remission in first episode
      psychosis (FEP) is a contentious area of practice. We aimed to investigate the
      views of early psychosis clinicians on this important clinical question. METHODS:
      We designed an 11 question online survey on medication discontinuation following
      remission of symptoms in FEP. The questionnaire was distributed to early
      intervention team workers in England and Wales via members of the National Early
      Psychosis Network who were requested to distribute it to their teams. RESULTS: We
      received 172 questionnaire responses; 37% were nurses, 33% doctors, 11%
      psychologists and 19% were other allied health professionals. The average years
      of experience in psychiatry was 16.9. 75.4% of respondents thought that greater
      than 60% of patients would like to be considered for guided medication
      reduction/discontinuation. Only 31.4% of respondents said that medication should
      be continued for over a year following remission. 61.4% of respondents felt that
      the quality of life of individuals was better in those who stop medication
      following remission. There was a significant difference in the response of
      professional groups to this question. 82.6% of respondents said they would be
      happy to support their patients in participating in a randomized trial of graded
      antipsychotic reduction/discontinuation versus maintenance medication.
      CONCLUSIONS: The views of clinicians regarding prophylactic antipsychotic
      medication following remission in FEP are much less conservative than those in
      current guidelines; concern was expressed by many about the impact of
      antipsychotic medication on quality of life. A randomized trial of maintenance
      antipsychotic medication versus graded reduction/discontinuation is feasible and
      has considerable clinician support.

PMID- 25962447
TI  - Features of cardioembolic stroke with persistent and paroxysmal atrial
      fibrillation - a study with the Japan Stroke Registry.
AB  - BACKGROUND AND PURPOSE: The stroke severity on admission and clinical outcomes
      were compared between ischaemic stroke patients with non-valvular atrial
      fibrillation (NVAF) of the persistent (PeAF) and paroxysmal (PAF) types. METHODS:
      The study comprised 9293 patients with cardioembolic stroke and NVAF who were
      registered in the Japanese stroke databank: 6522 had PeAF (70.2%) and 2771 had
      PAF (29.8%). Stroke severity on admission and the clinical outcomes on discharge
      were retrospectively compared between these patient groups. RESULTS: The National
      Institutes of Health Stroke Scale score on admission (median, interquartile
      range) was 10 (3-20) for PeAF patients and 7 (2-17) for PAF patients, indicating
      that stroke severity on admission was significantly worse in PeAF patients than
      PAF patients (P < 0.001). Good outcomes (modified Rankin scale score <=2) were
      achieved by 45% PeAF patients and 53% PAF patients. Thus, PeAF patients had
      significantly poorer clinical outcomes than PAF patients (P < 0.001). In-hospital
      mortality was significantly higher amongst PeAF patients (11%) than PAF patients
      (8%) (P < 0.001). Multivariate analysis of factors contributing to clinical
      outcomes showed that PeAF was a contributing factor for in-hospital mortality
      (odds ratio 1.261; 95% confidence interval 1.011-1.652; P = 0.045). CONCLUSIONS:
      Amongst cardioembolic stroke patients with NVAF, those with PeAF have
      significantly higher stroke severity on admission than those with PAF, and PeAF
      is a factor contributing to in-hospital mortality. Thus, our study suggests that
      the type of atrial fibrillation affects stroke severity and clinical outcomes
      following cerebral infarction.

PMID- 25962448
TI  - [Certified clinical excellence : Suitable tool for patient recruitment?].
AB  - BACKGROUND: Medical institutions often spend a lot of time and money to obtain
      external certification of clinical excellence and the quality of clinical care,
      with the purported aim of attracting patients. There is, however, little evidence
      about the role of certification in patients' choice of institution to receive
      elective inpatient treatment. OBJECTIVE: On admission 413 consecutive patients
      were anonymously surveyed about the reasons for choosing this institution, a
      tertiary care rheumatology department, which is currently certified by the
      cooperation for transparency and quality in healthcare (KTQ) and by the German
      Association of Rheumatological Acute Care Hospitals (VRA). In a self-administered
      questionnaire, patients reported reasons for their choice of institution,
      allowing for more than one reason. RESULTS: Patients reported recommendation by
      the primary care physician (48 %), recommendation by the attending rheumatologist
      (39 %), own (30 %) or family/friends (18 %) positive experience as the main
      reasons for choosing this institution. Certificates of clinical excellence were
      given as a reason by only 3 % of patients. Similar results were obtained from 42
      referring physicians, of which 5 % regarded the KTQ certification and 2 % the VRA
      certification as one of the decisive factors. CONCLUSION: The results suggest
      that certification does not meaningfully influence patient choice of clinic for
      elective inpatient treatment and therefore does not contribute to patient
      acquisition.

PMID- 25962449
TI  - [Rheumatism and kidney].

PMID- 25962450
TI  - [Interstitial nephritis in rheumatic diseases].
AB  - Interstitial nephritis is responsible for about 12 % of end-stage renal disease
      in Germany. It comprises an etiologically heterogenous group of inflammatory
      renal disorders which primarily affect the renal interstitium and tubuli. Drugs,
      predominantly antibiotics, nonsteroidal anti-inflammatory drugs and proton pump
      inhibitors are causative in the majority of cases. Rheumatic diseases frequently
      affect the kidneys, either the glomeruli or the interstitial tissues.
      Inflammatory interstitial processes can be accompanied by complex functional
      tubular disorders. This review gives an overview about clinical and laboratory
      findings of interstitial nephritis in the context of rheumatic diseases.
      Sarcoidosis, tubulointerstitial nephritis and uveitis (TINU) syndrome, primary
      Sjogren's syndrome, and IgG4-related disease often show an interstitial nephritis
      when the kidneys are affected. Other diseases, such as systemic lupus
      erythematosus, systemic sclerosis, drug reaction with eosinophilia and systemic
      symptoms (DRESS) syndrome, and granulomatosis with polyangiitis are more rarely
      associated with predominant interstitial nephritis. Glucocorticoids are the
      mainstay of therapy for most cases; in refractory cases or when side effects
      occur, second-line immunosuppressants such as mycophenolate mofetil, azathioprine
      and others, rarely biologics, can be used. 

PMID- 25962451
TI  - [Dosage and toxicity of antirheumatic drugs in renal insufficiency].
AB  - BACKGROUND: Patients with inflammatory rheumatic diseases frequently have a
      reduced renal function. The risk of adverse events is increased in these patients
      and treatment options in patients with rheumatic disease and renal failure are
      poorly studied. METHODS: A selective literature search was carried out for
      pharmocokinetics, dosage and toxicity of antirheumatic drugs in patients with
      renal insufficiency. RESULTS: The use of nonsteroidal anti-inflammatory drugs
      (NSAID), cyclooxygenase(COX)-2 inhibitors, gold and cyclosporine is limited in
      renal insufficiency due to nephrotoxicity. Methotrexate should not be used in
      patients with a glomerular filtration rate (eGFR) < 45 ml/min, because of the
      unpredictable pharmacokinetics with a risk for fatal pancytopenia. The dosage of
      sulfasalazine, azathioprine, mycophenolate mofetil, cyclophosphamide and
      antimalarial drugs should be reduced in patients with moderate and severe renal
      insufficiency. In contrast, leflunomide and numerous biologics can be used
      without dosage modification; however, biologics with a molecular weight < 60 kDa
      (e.g. anakinra) are an exception and should be reduced in patients with renal
      insufficiency. Overall, there are only limited data on the use of biologics in
      this population. Numerous comorbidities and the high risk for infection should be
      kept in mind when patients with rheumatic disease and renal failure are treated
      with immunosuppressive drugs. CONCLUSION: Further studies are necessary to obtain
      more evidence on the use of disease-modifying antirheumatic drugs (DMARD) and
      biologics in patients with renal insufficiency.

PMID- 25962452
TI  - [Prognosis and therapy of inflammatory rheumatic diseases : Impact of renal
      manifestations].
AB  - BACKGROUND: Inflammatory rheumatic diseases and their treatment cause various
      renal manifestations requiring modification of treatment. OBJECTIVES: Discussion
      of renal manifestations in selected rheumatic diseases, including their impact on
      general prognosis and therapy. MATERIALS AND METHODS: Basic literature and expert
      opinions are analyzed and discussed. RESULTS: Inflammatory rheumatic diseases and
      their treatment cause various renal manifestations, including glomerular,
      tubular, interstitial, and vascular damage. The type of damage determines both,
      associated clinical symptoms (i.e. hematuria, proteinuria, loss of kidney
      function) and the renal and overall survival as will be discussed here for
      rheumatoid arthritis, systemic lupus erythematosus, scleroderma, Sjogrens
      syndrome, cryoglobulinemia and ANCA-associated vasculitis. CONCLUSION: Renal
      manifestations are generally indicators of high disease activity and usually
      require more intensive treatment of the underlying rheumatic disease. Early and
      rigorous treatment, which has to be adapted to renal function, is capable of
      improving renal and overall survival in many of the affected patients.

PMID- 25962453
TI  - [Hyperuricemia - more than gout : Impact on cardiovascular risk and renal
      insufficiency].
AB  - BACKGROUND: Hyperuricemia is not only associated with gout but also with
      hypertension, atherosclerosis and chronic kidney disease (CKD); however, in cases
      of disproportionally high serum uric acid levels without symptoms of gout and
      slowly progressive chronic kidney failure especially in young people, a genetic
      cause of hyperuricemia needs to be considered. PATHOGENETIC ASSOCIATIONS: The
      results of experimental studies suggest that hyperuricemia can be a
      pathophysiologically relevant cardiovascular risk factor. In animal studies
      hyperuricemia leads to oxidative stress and vascular dysfunction and chronically
      elevated uric acid levels can result in structural changes of the vessel wall.
      Epidemiological data show a connection between hyperuricemia and hypertension and
      uric acid lowering therapy has been shown to lower arterial blood pressure. In
      CKD, uric acid increases in parallel with the decline in GFR and an increase in
      proteinuria. Several ongoing prospective clinical trials will clarify if
      pharmacological lowering of uric acid will translate into reduction of relevant
      cardiovascular and renal endpoints. THERAPY: The treatment of gout and the
      medicinal prophylaxis of further gout attacks depend on the comorbidities and
      especially CKD.

PMID- 25962454
TI  - [Relapsing polychondritis : A rare differential diagnosis in clinical practice].
AB  - Relapsing polychondritis (RPC) is a chronic immune-mediated inflammatory,
      systemic disease primarily leading to structural damage and impaired function of
      cartilage tissue. However, the systemic inflammatory process in RPC can also
      affect sensory organ structures, the respiratory tract, the nervous and
      cardiovascular systems as well as the kidneys. The immune-mediated disease leads
      to recurrent inflammatory attacks causing a progressive degradation of elastic
      and hyaline cartilage structures, especially in the ears, nose, larynx, trachea
      and diarthrodial joints. However, other connective tissue structures in the eye
      and the heart valves may also be involved. The RPC is regarded as an orphan
      disease as the number of reported cases has so far remained confined to
      approximately 600 worldwide. The rarity of the disease has limited systematic
      clinical studies and the available empirical data are exclusively derived from
      casuistic studies or evaluation of small case series. The therapeutic
      interventions depend on the extent and localization of the disease manifestation.
      Thus, nonsteroidal anti-inflammatory drugs (NSAID), glucocorticoids and
      immunosuppressive agents with conventional synthetic disease-modifying
      antirheumatic drugs (DMARD) have been demonstrated to be beneficial. More severe
      and refractory diseases may require a targeted pharmacological intervention with
      biologic DMARDs. 

PMID- 25962455
TI  - Autoimmune/auto-inflammatory syndrome induced by adjuvants (ASIA) after
      quadrivalent human papillomavirus vaccination in Colombians: a call for
      personalised medicine.
AB  - This was a case study in which 3 patients with autoimmune/auto-inflammatory
      syndrome induced by adjuvants (ASIA) after quadrivalent human papillomavirus
      vaccination (HPV) were evaluated and described. All the patients were women.
      Diagnosis consisted of HLA-B27 enthesitis related arthritis, rheumatoid arthritis
      and systemic lupus erythematous, respectively. Our results highlight the risk of
      developing ASIA after HPV vaccination and may serve to increase the awareness of
      such a complication. Factors that are predictive of developing autoimmune
      diseases should be examined at the population level in order to establish
      preventive measures in at-risk individuals for whom healthcare should be
      personalized and participatory. 

PMID- 25962456
TI  - A mathematical model of saccadic reaction time as a function of the fixation
      point brightness gain.
AB  - The gap effect refers to a reduction in saccadic reaction time (SRT) to an
      eccentric target, when the fixation point is removed before the target onset.
      Though it is known that the gap effect peaks when the fixation point is offset
      about 200 ms before the onset of the eccentric target, it is unknown how this
      effect is modulated by stimulus variations. In this paper, we propose and
      investigate a model of saccadic reaction time as a function of the fixation point
      brightness gain. The brightness gain is defined as the ratio of the final and
      initial intensities of the stimulus. We have conducted a typical gap effect
      experiment with 15 participants, where the brightness of the fixation point was
      manipulated under four conditions and two gap intervals, at the same time and 200
      ms before the onset of the eccentric target. The conditions included removing the
      fixation point (offset), leaving it with constant brightness (overlap), reducing,
      and increasing its brightness (lower and higher brightness conditions).
      Experimental data showed a significant gap effect in the offset and lower
      brightness conditions when compared to the overlap condition. On the other hand,
      the SRT was significantly longer for the higher brightness condition than the SRT
      for the overlap condition. Linear regression analysis using ten values of
      brightness gain shows that our model fits the data well for the 0- and 200-ms
      gap, with a coefficient of determination of .89 and .94, respectively. 

PMID- 25962457
TI  - Perceptual limits in a simulated "Cocktail party".
AB  - Numerosity judgments of simultaneous talkers were examined. Listeners were
      required to report the number of talkers heard when this number varied (1 to 13).
      Spatial location of talkers (1 or 6 locations), duration of talker voices (0.8 s,
      5.0 s, and 15.0 s), and gender arrangement of talkers also were manipulated in
      four experiments. In all experiments, the proportion of correct numerosity
      judgments monotonically decreased as talker numbers increased. Perceptual limits,
      defined as talker numbers with proportion correct scores of 0.5, varied between 3
      to 5 talkers, on average, depending on listening conditions, and were
      significantly higher for spatially separated talkers, for the longer voices, and
      for the mixed gender voices (Experiments 1, 2, and 3). In addition, Experiment 4
      found that average numerosity response times increased monotonically over a range
      of one to four talkers. These results support the idea that, before counting
      talkers, listeners perceptually segregate talkers to render numerosity judgments.
      They also suggest that our functional auditory world for simultaneous voices may
      consist of, at most, three to five talkers depending on listening situations. In
      light of these results, possible causes for such perceptual limits are discussed.

PMID- 25962458
TI  - Incompetence and failure to regulate methylisothiazolinone.

PMID- 25962459
TI  - Morphological characterisation and identification of four species of Cardicola
      Short, 1953 (Trematoda: Aporocotylidae) infecting the Atlantic bluefin tuna
      Thunnus thynnus (L.) in the Mediterranean Sea.
AB  - Blood flukes of the genus Cardicola Short, 1953 are considered the most
      potentially pathogenic parasites in bluefin tuna cultures. Morphological study
      and genetic analyses of the ribosomal internal transcribed spacer ITS-2 and the
      mitochondrial cytochrome c oxidase 1 (cox1) gene fragments revealed the
      occurrence of four aporocotylid species (C. forsteri Cribb, Daintith & Munday,
      2000, C. orientalis Ogawa, Tanaka, Sugihara & Takami, 2010, C. opisthorchis
      Ogawa, Ishimaru, Shirakashi, Takami & Grabner, 2011 and Cardicola sp.) in 421
      Thunnus thynnus (L.) from the Western Mediterranean (274 fished from the wild and
      147 from sea-cages). Cardicola opisthorchis was the most abundant species, with
      higher prevalence in the cage-reared fish than in those fished in the wild (21 vs
      6%, p < 0.05). Adults of three species were recovered: C. forsteri from both
      gills and heart, C. opisthorchis from heart and C. orientalis from gills. The
      secondary gill lamellae were profusely infected by eggs of C. orientalis. A
      fourth species was found in four tunas, based on the molecular analyses of eggs
      apparently indistinguishable in size and shape from the eggs of C. orientalis.
      The findings provided evidence that infections with Cardicola spp. differed in
      relation to locality, host origin (wild vs cage-reared) and site of infection. It
      is necessary to estimate the possible different pathogenic effects of each
      species of Cardicola in order to take appropriate control measures. 

PMID- 25962460
TI  - Studies on some spirurids (Nematoda: Spirurida) from fishes of the Okavango
      River, Botswana.
AB  - Based on light and scanning electron microscopical studies, three adult spirurid
      nematode species, Camallanus (Zeylanema) ctenopomae Vassiliades & Petter, 1972,
      Paracamallanus cyathopharynx (Baylis, 1923) (both Camallanidae) and Spinitectus
      polli Campana-Rouget, 1961 (Cystidicolidae), are redescribed from specimens
      collected in fishes of the Okavango River, Botswana: C. (Z.) ctenopomae from
      Ctenopoma sp. (Anabantidae), P. cyathopharynx from Clarias stappersi Boulenger,
      C. theodorae Weber (both new hosts, Clariidae) and C. gariepinus (Burchell), as
      well as S. polli from Synodontis nigromaculatus Boulenger (new host, Mochokidae).
      Moreover, spirurid larvae of an additional three species were found in fishes
      from the same locality: Rhabdochona paski Baylis, 1928 fourth-stage larva
      (Rhabdochonidae) in S. nigromaculatus (Mochokidae), Physalopteridae gen. sp. 1
      third-stage larva in C. gariepinus (Clariidae) and Physalopteridae gen. sp. 2
      third-stage larva in Serranochromis angusticeps (Boulenger) (Cichlidae), all
      representing new host and geographical records. Spinitectus zambezensis Boomker,
      1993 is considered a junior synonym of S. polli. 

PMID- 25962461
TI  - Solostamenides paucitesticulatus n. sp. (Monogenoidea: Mazocraeidea:
      Microcotylidae) from the freshwater mullet Liza abu (Heckel) (Mugiliformes:
      Mugilidae) from Ataturk Reservoir on the Euphrates River in southern Turkey.
AB  - Solostamenides paucitesticulatus n. sp. (Monogenoidea: Microcotylidae) from the
      gills of the abu mullet Liza abu (Heckel) in Ataturk Reservoir in southern Turkey
      is described. Among other features, the new species is easily distinguished from
      its three congeners, Solostamenides mugilis (Vogt, 1879), Solostamenides
      pseudomugilis (Hargis, 1956) and Solostamenides polyorchis Zhang & Yang, 2001, by
      having fewer hooks on the male copulatory organ (11 to 14), testes (5 to 9), and
      haptoral clamps (31 to 47). 

PMID- 25962462
TI  - Sharpilosentis peruviensis n. g., n. sp. (Acanthocephala: Diplosentidae) from
      freshwater catfishes (Siluriformes) in the Amazonia.
AB  - Sharpilosentis peruviensis n. g., n. sp. is described from the catfishes
      Duopalatinus cf. peruanus Eigenmann & Allen (type-host) and Oxydoras niger
      (Valenciennes) in the River Amazon basin, Peru. The new species belongs to the
      subfamily Diplosentinae Tubangui & Masilungan, 1937 of the family Diplosentidae
      Tubangui & Masilungan, 1937 because of its possession of an unarmed trunk, a
      cylindrical proboscis, proboscis hooks arranged in longitudinal rows and two
      tubular cement glands of the same length in males. Sharpilosentis n. g. differs
      from the other genera of the Diplosentidae in the morphology of the reproductive
      system: males have a large muscular penis covered with small tubercles and the
      vulva of females is devoid of muscular sphincters and the cephalic ganglion is
      located between the second and third part of the proboscis receptacle. In
      addition, proboscis hooks are of three types: large hooks with simple roots in
      the anterior part of the proboscis, transitional 6th hook in one from two
      adjacent rows with bifurcated root in the distal part and small hooks without
      roots in the posterior part of the proboscis. A partial sequence for the
      mitochondrial cox1 gene is provided for this new taxon. The taxonomic composition
      of the family Diplosentidae is discussed. 

PMID- 25962463
TI  - Redescription of Naobranchia variabilis Brian, 1924 (Siphonostomatoida:
      Lernaeopodidae), parasitic on the grey triggerfish Balistes capriscus Gmelin in
      Algerian coastal waters.
AB  - Adults of both sexes of Naobranchia variabilis Brian, 1924 (Lernaeopodidae) are
      described based on material collected from the gill filaments of Balistes
      capriscus Gmelin, caught off the coast of Algeria. This is the second species of
      Naobranchia Hesse, 1863 to be found in the Mediterranean and the host record is
      new. Morphological comparisons are made with existing descriptions of N.
      variabilis and it is inferred, from small variations between material from
      different hosts and different localities, that N. variabilis may represent a
      species complex. The corrugated lobes on the head of Naobranchia females are
      interpreted as novel structures involved with temporary attachment during
      feeding. 

PMID- 25962464
TI  - A new species of the genus Demodex Owen, 1843 (Acari: Demodecidae) from the ear
      canals of the house mouse Mus musculus L. (Rodentia: Muridae).
AB  - A new species Demodex conicus n. sp. is described based on adult and juvenile
      stages from the ear canals of the house mouse Mus musculus L. in Poland. The new
      species is most similar to D. auricularis Izdebska, Rolbiecki & Fryderyk, 2014
      from the ear canals of the wood mouse Apodemus sylvaticus (L.), but differs in
      the following features: the gnathosoma is triangular, the supracoxal spines
      (setae elc.p) are conical, the spines on the terminal segment of palp are four,
      the striation on opisthosoma is fine but dense, the vulva is located at a
      distance of c.17 um from posterior level of legs IV, and the male genital opening
      is located at the level of legs I. The differences also relate to body size and
      proportions, female D. conicus n. sp. being, on average slightly larger, and male
      significantly larger than D. auricularis. Males of the new species also have
      longer and more massive opisthosoma than males of D. auricularis. Demodex conicus
      n. sp. was found in 17.5% of the mice studied from different locations in Poland.

PMID- 25962465
TI  - Description of Litomosoides ysoguazu n. sp. (Nematoda, Onchocercidae), a parasite
      of the tuft-toed rice rat Sooretamys angouya (Fischer) (Rodentia: Cricetidae),
      and a first record of L. esslingeri Bain, Petit & Berteaux, 1989 in Paraguay.
AB  - Paraguay is a small landlocked country whose mammalian fauna is among the least
      studied in South America, as well as their parasites. As a result of a study of
      the effects of habitat fragmentation on small mammal biodiversity in eastern
      Paraguay, we have collected some parasites of cricetid rodents. Herein, we
      describe a new species of Litomosoides Chandler, 1931 parasitising the body
      cavity of the tuft-toed rice rat Sooretamys angouya (Fischer) and Litomosoides
      esslingeri Bain, Petit & Diagne, 1989 parasitising Oligoryzomys nigripes
      (Olfers), thus expanding its geographical distribution into Paraguay.
      Litomosoides ysoguazu n. sp. is characterised by the large size of the females
      (92.2-117.6 mm long) and by having buccal capsule with an anterior widening with
      rounded edges on the chitinous segment and a rounded widening at the base; male
      tail with a single pair of adcloacal papillae, three to five pairs of
      asymmetrical postcloacal papillae, and one or two unpaired papillae in the median
      ventral line; spicules corresponding to the "sigmodontis" species group; and
      microfilaria with a sheath stuck to the body and visible in the anterior
      extremity. We also describe a fourth-stage female larva. Oligoryzomys nigripes is
      a new host record of L. esslingeri; this enlarges the host record to eight
      species highlighting the low specificity of this species. 

PMID- 25962466
TI  - A new species of Eimeria Schneider, 1875 (Apicomplexa: Eimeriidae) from the brown
      anole Anolis sagrei Dumeril & Bibron (Sauria: Dactyloidae) in Florida, USA.
AB  - During July 2014, 14 brown anoles, Anolis sagrei Dumeril & Bibron were collected
      from Orange County, Florida, USA, and their faeces examined for coccidian
      parasites. One (7%) lizard harboured an eimerian that we describe here as new.
      Oocysts of Eimeria garmani n. sp. were ellipsoidal with a uni-layered wall and
      measured 19.3 * 12.5 um, with a length/width ratio of 1.5. A micropyle and oocyst
      residuum were absent but 1-2 polar granule(s) were present. Sporocysts were
      subspheroidal, 6.8 * 6.3 um, with a length/width ratio of 1.1. Stieda, sub-Stieda
      and para-Stieda bodies were absent. A sporocyst residuum was present as dispersed
      granules. Endogenous stages were observed within the small intestine. This is the
      first coccidian reported from the brown anole and the third eimerian reported
      from anoles in the United States. 

PMID- 25962467
TI  - Metabolic syndrome of weight change from pre-pregnancy to 1-5 years post-partum
      among Chinese women with prior gestational diabetes.
AB  - AIMS: Few studies have evaluated the effect of weight change from pre-pregnancy
      to post-partum with the risk of cardiometabolic diseases among women with a
      history of gestational diabetes mellitus. The aim of this study was to evaluate
      the association between weight change from pre-pregnancy to 1-5 years post-partum
      with metabolic syndrome among Chinese women with prior gestational diabetes
      mellitus. METHODS: We performed a retrospective cohort study in 1263 women with
      gestational diabetes mellitus at 1-5 years post-partum. Participants were divided
      into four groups based on their weight change from pre-pregnancy to 1-5 years
      post-partum: loss of >= 3 kg, +/- 3 kg, gain of 3-7 kg and gain of >=7 kg.
      RESULTS: The prevalence of metabolic syndrome was 12.1%, 16.2%, 26.0% and 44.3%
      among women with weight loss >= 3 kg, stable weight ( +/- 3 kg), weight gain 3-7
      kg and weight gain >= 7 kg from pre-pregnancy to post-partum, respectively. The
      positive association between weight change and metabolic syndrome was observed
      among women with pre-pregnancy normal weight (BMI < 24 kg/m(2)), overweight (BMI
      24-27.9 kg/m(2)) and obesity (BMI >= 28 kg/m(2)). The prevalence of metabolic
      syndrome was almost similar among pre-pregnancy normal weight women with weight
      gain >= 7 kg, pre-pregnancy overweight women with stable weight ( +/- 3 kg) and
      pre-pregnancy obese women with weight loss >= 3 kg from pre-pregnancy to post
      partum (P = 0.62). CONCLUSIONS: Women with gestational diabetes mellitus who had
      large weight gain from pre-pregnancy to post-partum were more likely to develop
      metabolic syndrome. Women who are pre-pregnancy overweight/obesity and also
      diagnosed as gestational diabetes mellitus during pregnancy need more weight
      control after delivery.

PMID- 25962468
TI  - Laminin L4 domain structure resembles adhesion modules in ephrin receptor and
      other transmembrane glycoproteins.
AB  - The ~ 800 kDa laminin heterotrimer forms a distinctive cross-shaped structure
      that further self-assembles into networks within the extracellular matrix. The
      domains at the laminin chain termini, which engage in network formation and cell
      surface interaction, are well understood both structurally and functionally. By
      contrast, the structures and roles of additional domains embedded within the
      limbs of the laminin cross have remained obscure. Here, we report the X-ray
      crystal structure, determined to 1.2 A resolution, of the human laminin alpha2
      subunit L4b domain, site of an inframe deletion mutation associated with mild
      congenital muscular dystrophy. The alpha2 L4b domain is an irregular beta
      sandwich with many short and broken strands linked by extended loops. The most
      similar known structures are the carbohydrate-binding domains of bacterial
      cellulases, the ephrin-binding domain of ephrin receptors, and MAM adhesion
      domains in various other eukaryotic cell-surface proteins. This similarity to
      mammalian adhesion modules, which was not predicted on the basis of amino acid
      sequence alone due to lack of detectable homology, suggests that laminin internal
      domains evolved from a progenitor adhesion molecule and may retain a role in cell
      adhesion in the context of the laminin trimer. DATABASE: The atomic coordinates
      and structure factors have been deposited in the Protein Data Bank, Research
      Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick,
      NJ, USA (http://www.rcsb.org/) under codes 4YEP and 4YEQ.

PMID- 25962469
TI  - [Metastasized prostate cancer. Position paper on the use of chemotherapy].
AB  - BACKGROUND: Antihormonal and cytotoxic therapy options are available for the
      therapy of metastasized prostate cancer (mPC). Because no comparative studies are
      available, especially for castration-resistant prostate cancer (mCRCP), it
      remains unclear which patients will profit best from which therapy. OBJECTIVES:
      Previous data on the sequence of the various therapy options show that correct
      selection of the first line therapy for mCRPC can have an influence on the
      prognosis of the patient. In this position paper the various therapy options are
      critically illustrated and the clinical and pathohistological criteria for
      selection of the first line therapy of mCRPC are discussed. RESULTS: Molecular
      markers are an important aid for future patient selection and individualized
      therapy for optimal use of the available forms of therapy.

PMID- 25962470
TI  - Elevations of serum CA-125 predict severity of acute appendicitis in males.
AB  - BACKGROUND: Acute appendicitis (AA) is a common indication for urgent abdominal
      surgery. CA-125 glycoprotein antigen is a non-specific marker for epithelial
      ovarian cancer; CA-125 serum levels also increased in the conditions of
      peritoneal inflammation. The aim of this study was to examine the correlation
      between serum CA-125 levels and AA. METHODS: All emergency department (ED)
      patients with suspected AA were prospectively enrolled in the study. The serum
      level of CA-125 was checked in every patient on arrival to the ED in addition to
      the routine clinical and laboratory evaluation. Data regarding demographic,
      clinical, radiological, operative and pathological features were analysed.
      RESULTS: One hundred consecutive patients (48 males) were enrolled in the study.
      We found a statistically significant correlation between CA-125 levels in males
      and the severity of appendicitis as described in the operative and pathology
      reports (P = 0.008 and P = 0.02, respectively). In addition, we observed a trend
      towards higher levels of CA-125 in males with AA compared with males without AA
      (9.9 +/- 4.7 versus 7.8 +/- 3.2 U/mL, respectively; P = 0.09). CONCLUSIONS: CA
      125 levels correlate with the severity of appendicitis in males and may serve as
      a surrogate marker for the severity of other intra-abdominal surgical diseases.

PMID- 25962472
TI  - Implementation of extended Lagrangian dynamics in GROMACS for polarizable
      simulations using the classical Drude oscillator model.
AB  - Explicit treatment of electronic polarization in empirical force fields used for
      molecular dynamics simulations represents an important advancement in simulation
      methodology. A straightforward means of treating electronic polarization in these
      simulations is the inclusion of Drude oscillators, which are auxiliary, charge
      carrying particles bonded to the cores of atoms in the system. The additional
      degrees of freedom make these simulations more computationally expensive relative
      to simulations using traditional fixed-charge (additive) force fields. Thus,
      efficient tools are needed for conducting these simulations. Here, we present the
      implementation of highly scalable algorithms in the GROMACS simulation package
      that allow for the simulation of polarizable systems using extended Lagrangian
      dynamics with a dual Nose-Hoover thermostat as well as simulations using a full
      self-consistent field treatment of polarization. The performance of systems of
      varying size is evaluated, showing that the present code parallelizes efficiently
      and is the fastest implementation of the extended Lagrangian methods currently
      available for simulations using the Drude polarizable force field.

PMID- 25962471
TI  - Failure in pantomime action execution correlates with the severity of social
      behavior deficits in children with autism: a praxis study.
AB  - Here we describe the performance of children with autism, their siblings, and
      typically developing children using the Florida Apraxia Battery. Children with
      autism showed the lowest performance in all sections of the test. They were
      mostly impaired in pantomime actions execution on imitation and on verbal
      command, and in imitation of meaningless gestures. Interestingly, a correlation
      was found between performance in pantomime actions and the severity of social
      behavior deficits. We conclude that the presence of a rigid internal model
      prevents the execution of an exact copy of the observed pantomime actions and
      that the deficit in imitation of meaningless gestures is most likely due to a
      deficit in the mechanisms responsible for visuomotor transformations. 

PMID- 25962473
TI  - CRF01_AE/B/C, a Novel Drug-Resistant HIV-1 Recombinant in Men Who Have Sex with
      Men in Beijing, China.
AB  - We report a unique HIV-1 recombinant strain (URF) from an HIV-positive man who
      has sex with men (MSM) in Beijing, China. This virus genome has insertions and
      multiple drug-resistant mutations to both nucleoside reverse transcriptase
      inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs),
      as well as a complex intersubtype recombinant structure with 11 breakpoints.
      Phylogenetic analysis of the near full-length genome (NFLG) shows that this URF
      is comprised of gene regions originating from three circulating viral strains:
      CRF01_AE, subtype B, and subtype C. The parental CRF01_AE regions of the
      recombinant cluster with a previously described cluster 4 sublineage of CRF01_AE.
      The B regions of the recombinant cluster within the B (United States-European
      origin) subtype and the three subtype C regions cluster with a strain detected in
      China in 1998. The detection and characterization of this complex drug-resistant
      URF indicate an ongoing generation of recombinant strains among MSM, and will
      help to provide insight into our understanding of the dynamics and complexity of
      the HIV-1 epidemic in China. 

PMID- 25962474
TI  - Predictors of medication nonadherence differ among black and white patients with
      heart failure.
AB  - Heart failure (HF) is a global public health problem, and outcomes remain poor,
      especially among ethnic minority populations. Medication adherence can improve
      heart failure outcomes but is notoriously low. The purpose of this secondary
      analysis of data from a prospective cohort comparison study of adults with heart
      failure was to explore differences in predictors of medication nonadherence by
      racial group (Black vs. White) in 212 adults with heart failure. Adaptive
      modeling analytic methods were used to model HF patient medication nonadherence
      separately for Black (31.7%) and White (68.3%) participants in order to
      investigate differences between these two racial groups. Of the 63 Black
      participants, 33.3% had low medication adherence, compared to 27.5% of the 149
      White participants. Among Blacks, 16 risk factors were related to adherence in
      bivariate analyses; four of these (more comorbidities, lower serum sodium, higher
      systolic blood pressure, and use of fewer activities compensating for
      forgetfulness) jointly predicted nonadherence. In the multiple risk factor model,
      the number of risk factors in Black patients ranged from 0 to 4, and 76.2% had at
      least one risk factor. The estimated odds ratio for medication nonadherence was
      increased 9.34 times with each additional risk factor. Among White participants,
      five risk factors were related to adherence in bivariate analyses; one of these
      (older age) explained the individual effects of the other four. Because Blacks
      with HF have different and more risk factors than Whites for low medication
      adherence, interventions are needed that address unique risk factors among Black
      patients with HF.

PMID- 25962475
TI  - Diagnosing domoic acid toxicosis in the California sea lion (Zalophus
      californianus) using behavioral criteria: A novel approach.
AB  - Domoic acid toxicosis in the California sea lion (Zalophus californianus) is
      difficult to diagnose using presence of toxin alone because the duration of
      domoic acid presence in blood and urine is generally less than 48 hr following
      exposure. Because domoic acid toxicosis is often suggested by presentation of
      behavioral abnormalities, we asked whether assessment of behavior might be useful
      for diagnostic purposes. We developed an ethogram to categorize behavioral data
      collected via continuous focal animal sampling. In total, 169 subjects were
      observed at a rehabilitation center. Sea lions with domoic acid toxicosis
      displayed head weaving (P < 0.0001) and muscle fasciculations (P < 0.01)
      significantly more often than animals in a comparison group. Dragging hind
      flippers and swift scanning were observed exclusively in animals from the domoic
      acid toxicosis group. The data show that behavioral diagnostic criteria can be
      effective in the diagnosis of domoic acid toxicosis in the California sea lion.

PMID- 25962476
TI  - Agitation in dementia and the role of spatial and sensory interventions:
      experiences of professional and family caregivers.
AB  - AIM: There is a growing interest in environmental interventions to complement the
      psychosocial approaches to cope with agitation in dementia. The aim of this study
      was to present this evidence from literature and research to care practitioners
      and family carers in order to gather their reflections. In this way, we can
      identify experienced gaps in care practice and define needs for further research.
      METHOD: A framework with seven types of environmental interventions for agitation
      in dementia was developed through literature review, referring to the impact of
      light, smell, noise, temperature, nature, colour and spatial configuration. This
      framework guided three expert panels, respectively, with family caregivers of
      persons with dementia (N = 5), professional home care workers (N = 12) and
      professional caregivers working in nursing homes (N = 10). RESULTS: All
      caregivers stressed the impact of agitation on their quality of life and on the
      quality of life of the person with dementia. Most caregivers were familiar with
      the impact of daylight, natural elements and domestic smells. Caregivers were
      unfamiliar with the specific effects of bright light therapy and were interested
      in more research on the effectiveness of light, temperature and spatial
      configuration. They stressed the individuality of agitation in dementia.
      CONCLUSION: Caregivers already use sensory and spatial interventions to manage
      agitation, and they are interested in knowing more about feasible effective
      interventions. Caregivers need to be informed on the possible benefits of sensory
      environmental factors on coping with agitation. To this end, it is very useful to
      take the experiences of caregivers into account.

PMID- 25962477
TI  - Prime-boost vaccination with Bacillus Calmette Guerin and a recombinant
      adenovirus co-expressing CFP10, ESAT6, Ag85A and Ag85B of Mycobacterium
      tuberculosis induces robust antigen-specific immune responses in mice.
AB  - Tuberculosis (TB) remains to be a prevalent health issue worldwide. At present,
      Mycobacterium bovis Bacillus Calmette Guerin (BCG) is the singular anti-TB
      vaccine available for the prevention of disease in humans; however, this vaccine
      only provides limited protection against Mycobacterium tuberculosis (Mtb)
      infection. Therefore, the development of alternative vaccines and strategies for
      increasing the efficacy of vaccination against TB are urgently required. The
      present study aimed to evaluate the ability of a recombinant adenoviral vector
      (Ad5-CEAB) co-expressing 10-kDa culture filtrate protein, 6-kDa early-secreted
      antigenic target, antigen 85 (Ag85)A and Ag85B of Mtb to boost immune responses
      following primary vaccination with BCG in mice. The mice were first
      subcutaneously primed with BCG and boosted with two doses of Ad5-CEAB via an
      intranasal route. The immunological effects of Ad5-CEAB boosted mice primed with
      BCG were then evaluated using a series of immunological indexes. The results
      demonstrated that the prime-boost strategy induced a potent antigen-specific
      immune response, which was primarily characterized by an enhanced T cell response
      and increased production of cytokines, including interferon-gamma, tumor necrosis
      factor-alpha and interleukin-2, in mice. In addition, this vaccination strategy
      was demonstrated to have an elevated humoral response with increased
      concentrations of antigen-specific bronchoalveolar lavage secretory
      immunoglobulin (Ig)A and serum IgG in mice compared with those primed with BCG
      alone. These data suggested that the regimen of subcutaneous BCG prime and
      mucosal Ad5-CEAB boost was a novel strategy for inducing a broad range of antigen
      specific immune responses to Mtb antigens in vivo, which may provide a promising
      strategy for further development of adenoviral-based vaccine against Mtb
      infection.

PMID- 25962478
TI  - Comparing the effects of massed and distributed practice on skill acquisition for
      children with autism.
AB  - We replicated and extended the findings of Haq and Kodak (2015) by evaluating the
      efficiency of massed and distributed practice for teaching tacts and textual and
      intraverbal behavior to 3 children with autism. Massed practice included all
      practice opportunities conducted on 1 day during each week, and distributed
      practice included practice opportunities conducted across several days during the
      week. The results indicated that distributed practice was more efficient for all
      participants. Suggested areas for future research and implications for practice
      are discussed. 

PMID- 25962479
TI  - Efficient perovskite/fullerene planar heterojunction solar cells with enhanced
      charge extraction and suppressed charge recombination.
AB  - Alcohol soluble titanium chelate TIPD (titanium (diisopropoxide) bis(2,4
      pentanedionate)) was used as an electron transporting layer to form an ohmic
      contact with the negative electrode, aiming to enhance the charge extraction and
      suppress the charge recombination for high performance CH3NH3PbI3/PCBM-based PHJ
      perovskite solar cells. The TIPD layer shows excellent suitability to CH3NH3PbI3
      perovskite synthesized by different methods. For one-step synthesized CH3NH3PbI3,
      the power conversion efficiency (PCE) of the device with the TIPD buffer reaches
      8.75%, with a nearly 33% increase in comparison with the device without the
      buffer layer (6.58%). For two-step synthesized CH3NH3PbI3, an open-circuit
      voltage (Voc) of 0.89 V, a short-circuit current density (Jsc) of 22.57 mA cm(
      2), and a fill factor (FF) of 64.5%, corresponding to a PCE of 12.95% for the
      device with a TIPD buffer layer were achieved, which is among the best
      performances reported in the literature for CH3NH3PbI3/PCBM-based PHJ perovskite
      solar cells. 

PMID- 25962480
TI  - Highly Water Resistant Anion Exchange Membrane for Fuel Cells.
AB  - For anion exchange membranes (AEMs), achieving efficient hydroxide conductivity
      without excessive hydrophilicity presents a challenge. Hence, new strategies for
      constructing mechanically strengthened and hydroxide conductive (especially at
      controlled humidity) membranes are critical for developing better AEMs.
      Macromolecular modification involving ylide chemistry (Wittig reaction) for the
      fabrication of novel AEMs with an interpenetrating polymer network structure is
      reported. The macromolecular modification is cost effective, facile, and based on
      a one-pot synthesis. AEM water uptake is reduced to 3.6 wt% and a high hydroxide
      conductivity (69.7 mS cm(-1) , 90  degrees C) is achieved simultaneously. More
      importantly, the membrane exhibits similar tensile strength (>35 MPa) and
      comparable flexibility in both dry and wet states. These AEMs could find further
      applications within anion exchange membrane fuel cells with low humidity or
      photoelectric assemblies. 

PMID- 25962481
TI  - Complete mitochondrial genome of a satyrid butterfly, Lethe albolineata
      (Lepidoptera: Nymphalidae).
AB  - The complete mitochondrial genome of Lethe albolineata is a circular molecule of
      15,248 bp in length, containing 13 protein-coding genes (PCGs), 22 transfer RNA
      genes (tRNAs), two ribosomal RNA genes (LrRNA and SrRNA), and a non-coding AT
      rich region. All PCGs use the standard ATN start codon, except for COI, which
      begins with CGA. Eight PCGs employ complete stop codon (TAA), whereas the others
      use a single T or TA acting as an incomplete stop codon. The AT-rich region is
      413 bp in length, which contains a conserved motif common to the other
      lepidopteran species. Two tRNA-like pseudo-genes are found in the mitochondrial
      genome of L. albolineata. The phylogenetic analysis shows that L. albolineata
      exhibits most close relationship with L. dura.

PMID- 25962482
TI  - Complete mitochondrial genome of the Macaca mulatta brevicaudus.
AB  - The complete mitochondrial sequence of the Macaca mulatta brevicaudus has been
      determined by mapping the raw data to previously published mitochondrial
      assemblies of the corresponding species. The total sequence length is 16,561 bp,
      consisting of 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA
      genes, and one D-loop control region. The base composition of the mtDNA genome is
      31.77% A, 25.14% T, 30.33% C, and 12.76% G, with an AT content of 56.90%. The
      arrangement of genes in M. m. brevicaudus is identical to that of M. mulatta. All
      genes are encoded on the heavy strand with the exception of ND6 and eight tRNA
      genes. The mitochondrial genome of M. m. brevicaudus presented here will
      contribute to a better understanding of the population genetics, help to protect
      its genetic diversity and resolve phylogenetic relationships within the family.

PMID- 25962483
TI  - The complete mitochondrial genome of Astatotilapia burtoni.
AB  - Astatotilapia burtoni is a species of fish in the Cichlidae family. Astatotilapia
      burtoni has been used as a model organism to research the behaviors and physical
      systems of cichlids. Here, we reported the complete mitogenome sequence of A.
      burtoni, which was 16,583 bp and composed of 13 protein-coding genes, 22 tRNA
      genes, 2 rRNA genes and 1 control region, with a base composition of lower G + C
      content (45.5%). Similar to Astatotilapia calliptera, all genes were located on H
      strand except for eight tRNAs and ND6 genes. Most protein-coding genes started
      with an ATG codon except for COX1, ATP6 and ND3, which initiated with GTG or ATC
      instead, and terminated with the typical stop condon (TAA/TAG)or a single T. In
      this article, 12 protein-coding genes of other 10 closely species were used to
      construct the species phylogenetic tree to convince the mitogenome sequences.
      These results provided basic information for researching A. burtoni on genetics,
      phylogeny and adaptive evolution.

PMID- 25962484
TI  - Identification of deer species (Cervidae, Cetartiodactyla) in China using
      mitochondrial cytochrome c oxidase subunit I (mtDNA COI).
AB  - In China, many deer species are threatened and their wild populations are
      decreasing. In this study, a segment of mitochondrial cytochrome oxidase subunit
      I (COI) was used as a DNA barcode to identify Cervidae species. COI sequences of
      30 individuals from nine species were determined. Together with 148 sequences
      from BOLD and Genbank, a total of 178 sequences from 21 species of the family
      Cervidae were analyzed. The results showed that all species had unique COI
      sequences, and there was no barcode sharing among them. The mean K2P distances
      within species, genus, and family were 1.3%, 3.4%, and 8.9%, respectively. The
      neighbor-joining (NJ) tree was in most cases concordant with modern deer
      classification. Three species showed maximum intraspecific divergences higher
      than their minimum interspecific divergences. However, all species could be
      discriminated by their diagnostic characters in BLOG analysis. The present study
      confirmed that COI barcodes can effectively distinguish Cervidae species in
      China.

PMID- 25962485
TI  - Complete mitochondrial genome of Siniperca roulei (Perciformes: Sinipercidae).
AB  - Siniperca roulei is an endemic species of the eastern part of China. In this
      study, the complete mitochondrial genome of S. roulei was determined. The
      circular genome is 16,493 bp in length and consists of 13 protein-coding genes,
      22 tRNA genes, two ribosomal RNA genes, and a control region. The overall
      nucleotide composition was 25.9% T, 29.3% C, 28.4% A, and 16.4% G, with an A + T
      bias of 54.3%. The gene composition and the arrangement of the S. roulei
      mitogenome were identical to most of the other vertebrates. The molecular data
      here we presented could play a useful role to study the evolutionary
      relationships and population genetics of Sinipercidae fish.

PMID- 25962486
TI  - Complete mitochondrial genome sequence of Ussurian moose, Alces alces cameloides.
AB  - Ussurian moose (Alces alces cameloides) in Northeast China, which is on the
      southmost edge of the species' Eurasian range, are facing dramatic decline in
      population size and distribution areas. We undertook the first sequencing of the
      entire mitogenome of Ussurian moose, which is thought as the oldest moose
      subspecies to better understand the evolutionary history of this circumboreal
      sole extant species. The mitogenome is 16,418 bp in length, consisting of two
      ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, 13 protein-coding
      genes, and one control region. The overall base composition is A: 33.7%, T:
      30.1%, C: 23.2%, and G: 13.0%, with a much higher A + T content. The phylogenetic
      tree of moose and 10 other most closely related Cervidae species was built.

PMID- 25962487
TI  - Ultrahigh Thermoelectric Performance in Mosaic Crystals.
AB  - Successful research strategies to enhance the dimensionless figure of merit zT
      above 2 rely on either bulk nanomaterials or on single crystals. A new physical
      mechanism of nanoscale mosaicity is shown that goes beyond the approaches in
      single crystals or conventional nanomaterials. A zT value of 2.1 at 1000 K in
      bulk nanomaterials is achieved. 

PMID- 25962488
TI  - Analysis of nitrogenous organic compounds from mainstream cigarette smoke using
      low-temperature solvent extraction followed by comprehensive two-dimensional gas
      chromatography with high-resolution time-of-flight mass spectrometry.
AB  - A method involving comprehensive two-dimensional gas chromatography coupled to
      high-resolution time-of-flight mass spectrometry was developed and applied to the
      analysis of nitrogenous organic compounds present in mainstream cigarette smoke
      trapped on self-designed equipment. The samples were prepared using low
      temperature solvent extraction under liquid nitrogen and analyzed by
      comprehensive two-dimensional gas chromatography with high-resolution time-of
      flight mass spectrometry. Important experimental parameters, such as the type and
      volume of the extraction solvent and flow rate of smoking, were optimized to
      improve the analysis parameter. The results indicated that 180 mL of diethyl
      ether in the low-temperature solvent extraction apparatus system with a 4 mL/min
      smoke flow rate were the optimal conditions. Then, 85 nitrogenous organic
      compounds were identified and quantified using a mass spectral library search,
      accurate mass ion and N-rules of a molecular formula for nitrogen compounds.
      Finally, a comparison of the low temperature solvent extraction method and
      Cambridge filter pad method indicated that more peaks, a higher peak volume and
      better repeatability were obtained using the low-temperature solvent extraction
      method. 

PMID- 25962489
TI  - Head and neck injuries from the Boston Marathon bombing at four hospitals.
AB  - The aim of this study was to evaluate the imaging findings of head and neck
      injuries in patients from the Boston Marathon bombing. A total of 115 patients
      from the Boston Marathon bombing presenting to four hospitals who underwent
      imaging to evaluate for head and neck injuries were included in the study. Twelve
      patients with positive findings on radiography or cross-sectional imaging were
      included in the final analysis. The radiographic, computed tomography (CT), and
      magnetic resonance (MR) imaging features of these patients were evaluated for the
      presence of shrapnel and morphological abnormality. Head and neck injuries were
      seen in 12 out of 115 patients presenting to the four hospitals. There were
      secondary blast injuries to the head and neck in eight patients, indicated by the
      presence of shrapnel on imaging. In the four patients without shrapnel, there
      were two with subgaleal hematomas, one with facial contusion and one with mastoid
      injury. There were two patients with subarachnoid hemorrhage, one with brain
      contusion, one with cerebral laceration, and one with globe rupture. There was
      frontal bone, nasal bone, and orbital wall fracture in one patient each. Imaging
      identified 26 shrapnel fragments, 21 of which were ball bearings. Injuries to the
      head and neck region identified on imaging from the Boston Marathon bombing were
      not common. The injuries seen were predominantly secondary blast injuries from
      shrapnel, and did not result in calvarial penetration of the shrapnel fragments. 

PMID- 25962490
TI  - Importance Attributed to Cardiovascular and Pulmonary Competencies by Public
      Sector Physical Therapists in Kuwait: A Population-based Exploratory Study.
AB  - BACKGROUND AND PURPOSE: Indications for cardiovascular and pulmonary (CVP)
      physical therapy competencies are changing with the epidemic of non-communicable
      diseases in Kuwait, particularly lifestyle-related conditions. The degree to
      which the country's physical therapists (PTs) perceive the importance of CVP
      competencies (assessment/evaluation and clinical and laboratory investigation
      interpretation) in professional practice is relevant. Our study objectives were
      to (1) explore the importance attributed to specific CVP competencies by PTs to
      professional practice in Kuwait and (2) establish whether these are related to
      practitioner traits, for example, age, sex, practice setting and specialty.
      METHOD: The study design was exploratory with a stratified random sample.
      Questionnaires (n = 221) were distributed to PTs practicing in the facilities of
      the Ministry of Health, the primary employer of PTs in Kuwait. Questions included
      participants' demographics and perceived importance of specific CVP competencies
      (Likert rating scale 1-not important to 5-highly important). RESULTS: Response
      rate was 87% (n = 193). Participant mean age was 36(+/-9) years, 63% were women
      and 48% were Kuwaiti. Ratings of moderately important or higher were 84% for
      cardiac assessment/intervention skills, 78.8% for cardiac clinical/laboratory
      investigations interpretation, 77.2% for pulmonary assessment/intervention skills
      and 73.6% for pulmonary clinical/laboratory investigations interpretation. PTs in
      the musculoskeletal area attributed less importance to the competencies than
      those in other specialties. CONCLUSIONS: Participants perceived CVP competencies
      as generally relevant to practice. However, greater importance was attributed to
      these competencies in relation to management of CVP conditions (e.g. those that
      address lifestyle-related conditions) rather than across practice areas. Research
      is needed to elucidate whether this finding reflects the profession's commitment
      to holistic care, the prevalence of lifestyle-related risk factors and conditions
      irrespective of a patient's primary complaint presenting to the PT, best evidence
      based, non-pharmacologic practice to address these or some combination. Copyright
      (c) 2015 John Wiley & Sons, Ltd.

PMID- 25962492
TI  - SHP-1 overexpression increases the radioresistance of NPC cells by enhancing DSB
      repair, increasing S phase arrest and decreasing cell apoptosis.
AB  - The present study aimed to investigate the influence of SHP-1 on the
      radioresistance of the nasopharyngeal carcinoma (NPC) cell line CNE-2 and the
      relevant underlying mechanisms. The human NPC cell line CNE-2 was transfected
      with a lentivirus that contained the SHP-1 gene or a nonsense sequence (referred
      to as LP-H1802Lv201 and LP-NegLv201 cells, respectively). Cells were irradiated
      with different ionizing radiation (IR) doses. Cell survival, DNA double-strand
      breaks (DSBs), apoptosis, cell cycle distribution, and the expression of related
      proteins were assessed using colony formation assay, immunofluorescent assays
      (IFAs), flow cytometry (FCM) and western blot analyses, respectively. Compared
      with the control (CNE-2 cells) and LP-NegLv201 cells, LP-H1802Lv201 cells were
      more resistant to IR. IFAs showed that IR caused less histone H2AX
      phosphorylation (gammaH2AX) and RAD51 foci in the LP-H1802Lv201 cells. Compared
      with the control and LP-NegLv201 cells, LP-H1802Lv201 cells showed increased S
      phase arrest. After IR, the apoptotic rate of the LP-H1802Lv201 cells was lower
      in contrast to the control and LP-NegLv201 cells. Western blot analyses showed
      that IR increased the phosphorylation of ataxia telangiectasia mutated (ATM)
      kinase, checkpoint kinase 2 (CHK2), ataxia telangiectasia and Rad3-related (ATR)
      protein, checkpoint kinase 1 (CHK1) and p53. In LP-H1802Lv201 cells, the
      phosphorylation levels of ATM and CHK2 were significantly increased while the p53
      phosphorylation level was decreased compared to these levels in the control and
      LP-NegLv201 cells. Phosphorylation of ATR and CHK1 did not show significant
      differences in the three cell groups. Overexpression of SHP-1 in the CNE-2 cells
      led to radioresistance and the radioresistance was related to enhanced DNA DSB
      repair, increased S phase arrest and decreased cell apoptosis.

PMID- 25962493
TI  - Synthesis and magnetic properties of manganese carbonyl complexes with different
      coordination modes of 3,4,5-triaryl-1,2-diphospholide ligands.
AB  - The set of complexes bis-(MU:eta(1),eta(1)-3,4,5-triaryl-1,2
      diphosphacyclopentadienyl)-bis-(tetracarbonyl manganese(i)) (aryl = C6H5 (), p
      FC6H4 (), p-ClC6H4 ()) undergo an irreversible rearrangement to mononuclear 3,4,5
      triaryl-1,2-diphosphacymantrenes (). According to quantum-chemical calculations
      binuclear complexes can be considered to be products of kinetic control and
      mononuclear species are thermodynamically favorable compounds. The
      antiferromagnetic intramolecular interaction observed for complexes can be
      effectively tuned by using substituents in the para-position of the arene ring,
      whereas mononuclear 1,2-diphosphacymantrenes are diamagnetic. 

PMID- 25962494
TI  - Avoidance of polypharmacy and excessive blood pressure control is associated with
      improved renal function in older patients.
AB  - BACKGROUND: Elderly patients are particularly susceptible to polypharmacy. The
      present study evaluated the renal effects of optimizing potentially nephrotoxic
      medications in an older population. METHODS: Retrospective study of patients' >=
      60 years treated between January of 2013 and February of 2015 in a Nephrology
      Clinic. The renal effect of avoiding polypharmacy was studied. RESULTS: Sixty-one
      patients were studied. Median age was 81 years (range 60-94). Twenty-five
      patients (41%) were male. NSAIDs alone were stopped in seven patients (11.4%), a
      dose reduction in antihypertensives was done in 11 patients (18%), one or more
      antihypertensives were discontinued in 20 patients (32.7%) and discontinuation
      and dose reduction of multiple medications was carried out in 23 patients
      (37.7%). The number of antihypertensives was reduced from a median of 3 (range of
      0-8) at baseline to a median of 2 (range 0-7), p < 0.001 after intervention.
      After intervention, the glomerular filtration rate (GFR) improved significantly,
      from a baseline of 32 +/- 15.5 cc/min/1.73 m(2) to 39.5 +/- 17 cc/min/1.73 m(2)
      at t1 (p < 0.001) and 44.5 +/- 18.7 cc/min/1.73 m(2) at t2 (p < 0.001 vs.
      baseline). In a multivariate model, after adjusting for ACEIs/ARBs
      discontinuation/dose reduction, NSAIDs use and change in DBP, an increase in SBP
      at time 1 remained significantly associated with increments in GFR on follow-up
      (estimate = 0.20, p = 0.01). CONCLUSIONS: Avoidance of polypharmacy was
      associated with an improvement in renal function.

PMID- 25962495
TI  - Outcomes of living kidney donors with monoclonal gammopathy of undetermined
      significance.

PMID- 25962496
TI  - Thermodynamics of various F420 coenzyme models as sources of electrons, hydride
      ions, hydrogen atoms and protons in acetonitrile.
AB  - 32 F420 coenzyme models with alkylation of the three different N atoms (N1, N3
      and N10) in the core structure (XFH(-)) were designed and synthesized and the
      thermodynamic driving forces (defined in terms of the molar enthalpy changes or
      the standard redox potentials in this work) of the 32 XFH(-) releasing hydride
      ions, hydrogen atoms and electrons, the thermodynamic driving forces of the 32
      XFH releasing protons and hydrogen atoms and the thermodynamic driving forces of
      XF(-) releasing electrons in acetonitrile were determined using titration
      calorimetry and electrochemical methods. The effects of the methyl group at N1,
      N3 and N10 and a negative charge on N1 and N10 atoms on the six thermodynamic
      driving forces of the F420 coenzyme models and their related reaction
      intermediates were examined; the results show that seating arrangements of the
      methyl group and the negative charge have remarkably different effects on the
      thermodynamic properties of the F420 coenzyme models and their related reaction
      intermediates. The effects of the substituents at C7 and C8 on the six
      thermodynamic driving forces of the F420 coenzyme models and their related
      reaction intermediates were also examined; the results show that the substituents
      at C7 and C8 have good Hammett linear free energy relationships with the six
      thermodynamic parameters. Meanwhile, a reasonable determination of possible
      reactions between members of the F420 family and NADH family in vivo was given
      according to a thermodynamic analysis platform constructed using the elementary
      step thermodynamic parameter of F420 coenzyme model 2FH(-) and NADH model MNAH
      releasing hydride ions in acetonitrile. The information disclosed in this work
      can not only fill a gap in the chemical thermodynamics of F420 coenzyme models as
      a class of very important organic sources of electrons, hydride ions, hydrogen
      atoms and protons, but also strongly promote the fast development of the
      chemistry and applications of F420 coenzyme. 

PMID- 25962497
TI  - Donkey Milk for Manufacture of Novel Functional Fermented Beverages.
AB  - The aim of this work was to investigate on the functional features of a donkey
      milk probiotic berevage as a novel food. Particularly, it was to study the
      decrease of lactose content and the antioxidant activity of standard yogurt (YC)
      and probiotic yogurt (YP; Lactobacillus acidophilus, Lactobacillus casei) from
      donkey milk during the storage up to 30 d at 4 oC. The evolution of lactose
      content using enzymatic-spectrophotometric kits was analyzed. Antioxidant
      activity of yogurt was measured using 2,2'-azino-bis-3-ethylbenzothiazoline-6
      sulfonic acid (ABTS), ferric reducing antioxidant power (FRAP), and thiol assays.
      Parallel consumer sensory studies were carried out as consumer test in order to
      gain information about the impact of these novel fermented beverages on sensory
      perceptions. The statistical analysis has shown significant effect of studied
      factors. The results showed that the lactose content gradually decreased during
      storage in both yogurts, reaching values of 2.36% and 2.10% in YC and YP,
      respectively, at 30 d (P < 0.05). During storage of both yogurt types, the
      antioxidant activity increased, but YP showed a higher antioxidant activity than
      YC. The results suggest that the antioxidant activity of yogurt samples was
      affected by cultures of lactic acid bacteria (LAB). We conclude that the
      fermented donkey milk could be configured as health and nutraceutical food, which
      aims to meet nutritional requirements of certain consumers groups with lactose or
      cow milk protein intolerance. 

PMID- 25962499
TI  - Abstracts of the 41st annual meeting of the society for neuropediatrics.

PMID- 25962498
TI  - Sterile males in a parasitoid wasp with complementary sex determination: from
      fitness costs to population extinction.
AB  - BACKGROUND: Single-locus complementary sex determination (sl-CSD), which occurs
      in some insects of the order Hymenoptera, imposes a heavy genetic load that can
      drive small populations to extinction. The core process in these species is the
      development of individuals homozygous at the sex-determining locus into unfit
      diploid males. The risk of extinction of populations with sl-CSD is theoretically
      much higher if diploid males are viable and capable of mating but sterile,
      because diploid males then decrease the reproductive output of both their parents
      and the females with which they mate. RESULTS: In the parasitoid wasp Venturia
      canescens (Hymenoptera: Ichneumonidae), diploid males resembled their haploid
      counterparts in most respects, but their mating success was nevertheless lower
      than that of haploid males, especially when the two types of males were placed in
      competition. Furthermore, although diploid males transferred viable sperm during
      copulation, they sired no daughters: the females with which they mated produced
      only sons, like virgin females. A simulation model combining behavior, genetics
      and demography demonstrated that for two alternative hypotheses concerning the
      fertilization success of diploid sperm, the mating success of diploid males
      strongly affected population dynamics. CONCLUSION: The performance of diploid
      males should be estimated in competitive situations. It is a crucial determinant
      of the probability of extinction.

PMID- 25962500
TI  - Changing priorities in women's health.

PMID- 25962501
TI  - The Danish Fetal Medicine Database: revealing the fruits of collaborative
      research.

PMID- 25962502
TI  - Dynamic transcriptome profiles of skeletal muscle tissue across 11 developmental
      stages for both Tongcheng and Yorkshire pigs.
AB  - BACKGROUND: The growth and development of skeletal muscle directly impacts the
      quantity and quality of pork production. Chinese indigenous pig breeds and exotic
      species vary greatly in terms of muscle production and performance traits. We
      present transcriptome profiles of 110 skeletal muscle samples from Tongcheng (TC)
      and Yorkshire (YK) pigs at 11 developmental periods (30, 40, 55, 63, 70, 90, and
      105 days of gestation, and 0, 1, 3, and 5 weeks of age) using digital gene
      expression on Solexa/Illumina's Genome Analyzer platform to investigate the
      differences in prenatal and postnatal skeletal muscle between the two breeds.
      RESULTS: Muscle morphological changes indicate the importance of primary fiber
      formation from 30 to 40 dpc (days post coitus), and secondary fiber formation
      from 55 to 70 dpc. We screened 4,331 differentially expressed genes in TC and
      2,259 in YK (log2 ratio >1 and probability >0.7). Cluster analysis showed
      different gene expression patterns between TC and YK pigs. The transcripts were
      annotated in terms of Gene Ontology related to muscle development. We found that
      the genes CXCL10, EIF2B5, PSMA6, FBXO32, and LOC100622249 played vital roles in
      the muscle regulatory networks in the TC breed, whereas the genes SGCD, ENG,
      THBD, AQP4, and BTG2 played dominant roles in the YK breed. These genes showed
      breed-specific and development-dependent differential expression patterns.
      Furthermore, 984 genes were identified in myogenesis. A heat map showed that
      significantly enriched pathways (FDR <0.05) had stage-specific functional
      regulatory mechanisms. Finally, the differentially expressed genes from our
      sequencing results were confirmed by real-time quantitative polymerase chain
      reaction. CONCLUSIONS: This study detected many functional genes and showed
      differences in the molecular mechanisms of skeletal muscle development between TC
      and YK pigs. TC pigs showed slower muscle growth and more complicated genetic
      regulation than YK pigs. Many differentially expressed genes showed breed
      specific expression patterns. Our data provide a better understanding of skeletal
      muscle developmental differences and valuable information for improving pork
      quality.

PMID- 25962503
TI  - Significance of prophylactic intra-abdominal drain placement after laparoscopic
      distal gastrectomy for gastric cancer.
AB  - BACKGROUND: Unnecessary intra-abdominal drain insertion must be avoided, but
      little is known about the value of prophylactic drainage following laparoscopic
      distal gastrectomy (LDG). In this study, we investigated the significance of
      prophylactic drain placement after LDG for gastric cancer. METHODS: Seventy-eight
      consecutive patients with gastric cancer who underwent LDG in our department were
      retrospectively analyzed. The patients were divided into two groups according to
      the insertion of a prophylactic intra-abdominal drain following LDG. The 'drain
      group' comprised 45 patients with routine use of a prophylactic intra-abdominal
      drain, and the 'no-drain group' comprised 33 patients who did not undergo
      placement of an intra-abdominal drain. RESULTS: There were no significant
      differences in terms of the mean age of the patients, male/female ratio, body
      mass index, and concurrent diseases between the drain group and the no-drain
      group. In addition, there were no significant differences in the tumor location,
      tumor diameter, depth of the tumor, nodal metastasis, and tumor stage between the
      two groups. All patients in each group were successfully treated with R0 surgery,
      and no patient required conversion to open surgery. Surgery-related factors,
      including lymph node dissection and operative time, were similar in the drain
      group and the no-drain group. A comparison of the amount of intraoperative blood
      loss between patients with and without postoperative complications revealed that
      patients who experienced postoperative complications had a significantly larger
      amount of blood loss than those without postoperative complications. A comparison
      of operative times between patients with and without surgery-related
      postoperative local complications revealed that patients who experienced surgery
      related postoperative local complications had a significantly longer operative
      time than those without surgery-related postoperative local complications.
      Analysis of operative times in each group revealed that patients with surgery
      related postoperative local complications had a significantly longer operative
      time than those without surgery-related postoperative local complications in the
      no-drain group. CONCLUSIONS: Intraoperative factors such as the operative time
      and the amount of intraoperative blood loss affected the occurrence of
      postoperative complications following LDG. A prophylactic drain may thus be
      useful in patients at higher risk and in those with a longer operative time or
      massive intraoperative bleeding.

PMID- 25962504
TI  - Current CAPE-15: a measure of recent psychotic-like experiences and associated
      distress.
AB  - AIM: Psychotic-like experiences (PLEs) are common in young people and are
      associated with both distress and adverse outcomes. The Community Assessment of
      Psychic Experiences-Positive Scale (CAPE-P) provides a 20-item measure of
      lifetime PLEs. A 15-item revision of this scale was recently published (CAPE
      P15). Although the CAPE-P has been used to assess PLEs in the last 12 months,
      there is no version of the CAPE for assessing more recent PLEs (e.g. 3 months).
      This study aimed to determine the reliability and validity of the current CAPE
      P15 and assess its relationship with current distress. METHOD: A cross-sectional
      online survey of 489 university students (17-25 years) assessed lifetime and
      current substance use, current distress, and lifetime and 3-month PLEs on the
      CAPE-P15. RESULTS: Confirmatory factor analysis indicated that the current CAPE
      P15 retained the same three-factor structure as the lifetime version consisting
      of persecutory ideation, bizarre experiences and perceptual abnormalities. The
      total score of the current version was lower than the lifetime version, but the
      two were strongly correlated (r = .64). The current version was highly predictive
      of generalized distress (r = .52) and indices that combined symptom frequency
      with associated distress did not confer greater predictive power than frequency
      alone. CONCLUSION: This study provided preliminary data that the current CAPE-P15
      provides a valid and reliable measure of current PLEs. The current CAPE-P15 is
      likely to have substantial practical utility if it is later shown to be sensitive
      to change, especially in prevention and early intervention for mental disorders
      in young people.

PMID- 25962505
TI  - Simple, fast matrix conversion and membrane separation method for ultrasensitive
      metal detection in aqueous samples by laser-induced breakdown spectroscopy.
AB  - A fast, low cost, and sensitive sample pretreatment method was specially
      developed for laser-induced breakdown spectroscopy (LIBS) based on metal
      precipitation and membrane separation for simultaneous elemental analysis in
      liquid samples. The metal elements were reacted with the chelating reagent 2,4,6
      trimercapto-1,3,5-triazine (TMT) in the first step and separated by mixed
      cellulose ester microfiltration membrane subsequently. A specific membrane
      supporter with smaller aperture than the commercially available needle filter was
      designed and assembled in the presented research to increase the sensitivity. As
      a result, the detection limits of Cu, Ag, Mn, and Cr obtained in this research
      were 2.59 ng.mL(-1), 0.957 ng.mL(-1), 0.958 ng.mL(-1), and 1.29 ng.mL(-1)
      respectively, which were greatly improved from direct liquid analysis by LIBS.
      Satisfactory linearity, reproducibility, and accuracy were also obtained in the
      concentration range of 10-120 ng.mL(-1) for all four elements tested at the
      optimized experimental conditions. The analytical figures of merits of the
      proposed method are at an advanced level and are comparable to those reported
      among other non-LIBS research. In addition, the separation mechanism in this
      research was initially explored and further varied to be based on metal
      precipitates adsorption by membrane fibers, rather than a regular size-dependent
      obstruction. 

PMID- 25962506
TI  - Urolithin A causes p21 up-regulation in prostate cancer cells.
AB  - PURPOSE: Walnuts contain several bioactive compounds, including pedunculagin, a
      polyphenol metabolized by microbiota to form urolithins, namely urolithin A (UA).
      The aim of this study was to determine gene expression changes in prostate cancer
      cells after incubation with UA. METHODS: We performed a genomic analysis to study
      the effect of UA on LNCaP prostate cells. Cells were incubated with 40 uM UA for
      24 h, and RNA was extracted and hybridized to Affymetrix Human Genome U219 array.
      Microarray results were analyzed using GeneSpring v13 software. Differentially
      expressed genes (p < 0.05, fold change > 2) were used to perform biological
      association networks. Cell cycle was analyzed by flow cytometry and apoptosis
      measured by the rhodamine method and by caspases 3 and 7 activation. Cell
      viability was determined by MTT assay. RESULTS: We identified two nodes, FN-1 and
      CDKN1A, among the differentially expressed genes upon UA treatment. CDKN1A was
      validated, its mRNA and protein levels were significantly up-regulated, and the
      promoter activation measured by luciferase. Cell cycle analysis showed an
      increase in G1-phase, and we also observed an induction of apoptosis and caspases
      3 and 7 activation upon UA treatment. CONCLUSION: Our results indicate a
      potential role of UA as a chemopreventive agent for prostate cancer.

PMID- 25962507
TI  - Vitamin D, vitamin D binding protein gene polymorphisms, race and risk of
      incident stroke: the Atherosclerosis Risk in Communities (ARIC) study.
AB  - BACKGROUND AND PURPOSE: Low vitamin D levels, measured by serum 25-hydroxyvitamin
      D [25(OH)D], are associated with increased stroke risk. Less is known about
      whether this association differs by race or D binding protein (DBP) single
      nucleotide polymorphism (SNP) status. Our objective was to characterize the
      associations of and interactions between 25(OH)D levels and DBP SNPs with
      incident stroke. It was hypothesized that associations of low 25(OH)D with stroke
      risk would be stronger amongst persons with genotypes associated with higher DBP
      levels. METHODS: 25(OH)D was measured by mass spectroscopy in 12 158 participants
      in the Atherosclerosis Risk in Communities (ARIC) study (baseline 1990-1992, mean
      age 57 years, 57% female, 23% black) and they were followed through 2011 for
      adjudicated stroke events. Two DBP SNPs (rs7041, rs4588) were genotyped. Cox
      models were adjusted for demographic/behavioral/socioeconomic factors. RESULTS:
      During a median of 20 years follow-up, 804 incident strokes occurred. The lowest
      quintile of 25(OH)D (<17.2 ng/ml) was associated with higher stroke risk [hazard
      ratio (HR) 1.34 (1.06-1.71) versus highest quintile]; this association was
      similar by race (P interaction 0.60). There was weak evidence of increased risk
      of stroke amongst those with 25(OH)D < 17.2 ng/ml and either rs7041 TG/GG [HR =
      1.29 (1.00-1.67)] versus TT genotype [HR = 1.19 (0.94-1.52)] (P interaction 0.28)
      or rs4588 CA/AA [HR = 1.37 (1.07-1.74)] versus CC genotype [HR = 1.14 (0.91
      1.41)] (P interaction 0.11). CONCLUSIONS: Low 25(OH)D is a risk factor for
      stroke. Persons with low 25(OH)D who are genetically predisposed to high DBP
      (rs7041 G, rs4588 A alleles), who therefore have lower predicted bioavailable
      25(OH)D, may be at greater risk for stroke, although our results were not
      conclusive and should be interpreted as hypothesis generating.

PMID- 25962508
TI  - Cytokine-induced killer (CIK) cells: from basic research to clinical translation.
AB  - The accumulation of basic researches and clinical studies related to cytokine
      induced killer (CIK) cells has confirmed their safety and feasibility in treating
      malignant diseases. This review summarizes the available published literature
      related to the biological characteristics and clinical applications of CIK cells
      in recent years. A number of clinical trials with CIK cells have been implemented
      during the progressive phases of cancer, presenting potential widespread
      applications of CIK cells for the future. Furthermore, this review briefly
      compares clinical applications of CIK cells with those of other adoptive
      immunotherapeutic cells. However, at present, there are no uniform criteria or
      large-scale preparations of CIK cells. The overall clinical response is difficult
      to evaluate because of the use of autologous CIK cells. Based on these
      observations, several suggestions regarding uniform criteria and universal
      sources for CIK cell preparations and the use of CIK cells either combined with
      chemotherapy or alone as a primary strategy are briefly proposed in this review.
      Large-scale, controlled, grouped, and multi-center clinical trials on CIK cell
      based immunotherapy should be conducted under strict supervision. These
      interventions might help to improve future clinical applications and increase the
      clinical curative effects of CIK cells for a broad range of malignancies in the
      future. 

PMID- 25962509
TI  - Autoantigen cross-reactive environmental antigen can trigger multiple sclerosis
      like disease.
AB  - BACKGROUND: Multiple sclerosis is generally considered an autoimmune disease
      resulting from interaction between predisposing genes and environmental factors,
      together allowing immunological self-tolerance to be compromised. The precise
      nature of the environmental inputs has been elusive, infectious agents having
      received considerable attention. A recent study generated an algorithm predicting
      naturally occurring T cell receptor (TCR) ligands from the proteome database.
      Taking the example of a multiple sclerosis patient-derived anti-myelin TCR, the
      study identified a number of stimulatory, cross-reactive peptide sequences from
      environmental and human antigens. Having previously generated a spontaneous
      multiple sclerosis (MS) model through expression of this TCR, we asked whether
      any of these could indeed function in vivo to trigger CNS disease by cross
      reactive activation. FINDINGS: A number of myelin epitope cross-reactive epitopes
      could stimulate T cell immunity in this MS anti-myelin TCR transgenic model. Two
      of the most stimulatory of these 'environmental' epitopes, from Dictyostyelium
      slime mold and from Emiliania huxleyi, were tested for the ability to induce MS
      like disease in the transgenics. We found that immunization with cross-reactive
      peptide from Dictyostyelium slime mold (but not from E. huxleyi) induces severe
      disease. CONCLUSIONS: These specific environmental epitopes are unlikely to be
      common triggers of MS, but this study suggests that our search for the cross
      reactivity triggers of autoimmune activation leading to MS should encompass
      epitopes not just from the 'infectome' but also from the full environmental
      'exposome.'

PMID- 25962510
TI  - Value of monoenergetic dual-energy CT (DECT) for artefact reduction from metallic
      orthopedic implants in post-mortem studies.
AB  - OBJECTIVES: The aim of this ex vivo study was to assess the performance of
      monoenergetic dual-energy CT (DECT) reconstructions to reduce metal artefacts in
      bodies with orthopedic devices in comparison with standard single-energy CT
      (SECT) examinations in forensic imaging. Forensic and clinical impacts of this
      study are also discussed. MATERIALS AND METHODS: Thirty metallic implants in 20
      consecutive cadavers with metallic implants underwent both SECT and DECT with a
      clinically suitable scanning protocol. Extrapolated monoenergetic DECT images at
      64, 69, 88, 105, 120, and 130 keV and individually adjusted monoenergy for
      optimized image quality (OPTkeV) were generated. Image quality of the seven
      monoenergetic images and of the corresponding SECT image was assessed
      qualitatively and quantitatively by visual rating and measurements of attenuation
      changes induced by streak artefact. RESULTS: Qualitative and quantitative
      analyses showed statistically significant differences between monoenergetic DECT
      extrapolated images and SECT, with improvements in diagnostic assessment in
      monoenergetic DECT at higher monoenergies. The mean value of OPTkeV was 137.6 +/-
      4.9 with a range of 130 to 148 keV. CONCLUSIONS: This study demonstrates that
      monoenergetic DECT images extrapolated at high energy levels significantly reduce
      metallic artefacts from orthopedic implants and improve image quality compared to
      SECT examination in forensic imaging.

PMID- 25962511
TI  - Fairness influences early signatures of reward-related neural processing.
AB  - Many humans exhibit a strong preference for fairness during decision-making.
      Although there is evidence that social factors influence reward-related and
      affective neural processing, it is unclear if this effect is mediated by
      compulsory outcome evaluation processes or results from slower deliberate
      cognition. Here we show that the feedback-related negativity (FRN) and late
      positive potential (LPP), two signatures of early hedonic processing, are
      modulated by the fairness of rewards during a passive rating task. We find that
      unfair payouts elicit larger FRNs than fair payouts, whereas fair payouts elicit
      larger LPPs than unfair payouts. This is true both in the time-domain, where the
      FRN and LPP are related, and in the time-frequency domain, where the two signals
      are largely independent. Ultimately, this work demonstrates that fairness affects
      the early stages of reward and affective processing, suggesting a common
      biological mechanism for social and personal reward evaluation. 

PMID- 25962512
TI  - Contact dermatitis caused by Tinosorb(r) M: the importance of pach testing with
      pure methylene bis-benzotriazolyl tetramethylbutylphenol.

PMID- 25962513
TI  - Body mass index and response to infliximab in rheumatoid arthritis.
AB  - OBJECTIVES: Excess adipose tissue in obese individuals may have immunomodulating
      properties and pharmacokinetics consequences. Previous studies have suggested
      that obesity could negatively affect the response to anti-TNF-alpha agents,
      notably infliximab (IFX). We aimed to determine whether body mass index (BMI) is
      involved in the response to IFX in rheumatoid arthritis (RA). METHODS: We
      retrospectively examined data for 76 RA patients receiving IFX. BMI was
      calculated before treatment, and change from baseline in DAS28, pain on a visual
      analog scale, erythrocyte sedimentation rate, C-reactive protein level, tender
      and swollen joint count was analysed at 6 months after treatment. The primary
      outcome was decrease in DAS28 >=1.2. Secondary outcomes were good response and
      remission according to EULAR. RESULTS: At baseline, the median [interquartile
      range] BMI was 26.6 [22.6-30.6] kg/m2. The number of patients with normal weight,
      overweight and obesity was 25, 29 and 22. In multivariable analyses, IFX treated
      patients with lower BMI showed a more frequent DAS28 decrease >=1.2 (25.5 [22.3
      28.3] vs. 28.0 [23.2-32.5], p=0.02, odds ratio [OR] 0.88 [95% confidence interval
      0.79-0.98]), EULAR good response (25.3 [21.9-27.5] vs. 27.5 [24.3-31.2], p=0.03,
      OR 0.87 [0.76-0.99]) and EULAR remission, although not significant (25.3 [21.9
      26.4] vs. 27.5 [23.2-30.9], p=0.14, OR 0.88 [0.75-1.04]). CONCLUSIONS: Obesity
      may negatively influence the response to IFX in RA. These data could help
      physicians to choose biologic agents for obese RA patients.

PMID- 25962515
TI  - OPTIMAL, an occupational therapy led self-management support programme for people
      with multimorbidity in primary care: a randomized controlled trial.
AB  - BACKGROUND: We investigated the effectiveness of an occupational therapy led self
      management support programme, OPTIMAL, designed to address the challenges of
      living with multiple chronic conditions or multimorbidity in a primary care
      setting. METHODS: Pragmatic feasibility randomised controlled trial including
      fifty participants with multimorbidity recruited from family practice and primary
      care settings. OPTIMAL is a six-week community-based programme, led by
      occupational therapy facilitators and focuses on problems associated with
      managing multimorbidity. The primary outcome was frequency of activity
      participation. Secondary outcomes included self-perception of, satisfaction with
      and ability to perform daily activities, independence in activities of daily
      living, anxiety and depression, self-efficacy, health-related quality of life,
      self-management support, healthcare utilisation and individualised goal
      attainment. Outcomes were collected within two weeks of intervention completion.
      RESULTS: There was a significant improvement in frequency of activity
      participation, measured using the Frenchay Activities Index, for the intervention
      group compared to the control group (Adjusted Mean Difference at follow up 4.22.
      95% Confidence Interval 1.59-6.85). There were also significant improvements in
      perceptions of activity performance and satisfaction, self-efficacy, independence
      in daily activities and quality of life. Additionally, the intervention group
      demonstrated significantly higher levels of goal achievement, following the
      intervention. No significant differences were found between the two groups in
      anxiety, depression, self-management scores or healthcare utilisation.
      CONCLUSIONS: OPTIMAL significantly improved frequency of activity participation,
      self-efficacy and quality of life for patients with multimorbidity. Further work
      is required to test the sustainability of these effects over time but this study
      indicates that it is a promising intervention that can be delivered in primary
      care and community settings. TRIAL REGISTRATION:  TRIAL NUMBER: ISRCTN67235963.

PMID- 25962514
TI  - Microgeography and molecular epidemiology of malaria at the Thailand-Myanmar
      border in the malaria pre-elimination phase.
AB  - BACKGROUND: Endemic malaria in Thailand continues to only exist along
      international borders. This pattern is frequently attributed to importation of
      malaria from surrounding nations. A microgeographical approach was used to
      investigate malaria cases in a study village along the Thailand-Myanmar border.
      METHODS: Three mass blood surveys were conducted during the study period (July
      and December 2011, and May 2012) and were matched to a cohort-based demographic
      surveillance system. Blood slides and filter papers were taken from each
      participant. Slides were cross-verified by an expert microscopist and filter
      papers were analysed using nested PCR. Cases were then mapped to households and
      analysed using spatial statistics. A risk factor analysis was done using mixed
      effects logistic regression. RESULTS: In total, 55 Plasmodium vivax and 20
      Plasmodium falciparum cases (out of 547 participants) were detected through PCR,
      compared to six and two (respectively) cases detected by field microscopy. The
      single largest risk factor for infection was citizenship. Many study participants
      were ethnic Karen people with no citizenship in either Thailand or Myanmar. This
      subpopulation had over eight times the odds of malaria infection when compared to
      Thai citizens. Cases also appeared to cluster near a major drainage system and
      year-round water source within the study village. CONCLUSION: This research
      indicates that many cases of malaria remain undiagnosed in the region. The
      spatial and demographic clustering of cases in a sub-group of the population
      indicates either transmission within the Thai village or shared exposure to
      malaria vectors outside of the village. While it is possible that malaria is
      imported to Thailand from Myanmar, the existence of undetected infections,
      coupled with an ecological setting that is conducive to malaria transmission,
      means that indigenous transmission could also occur on the Thai side of the
      border. Improved, timely, and active case detection is warranted.

PMID- 25962516
TI  - The contribution of apixaban renal clearance to total clearance.

PMID- 25962517
TI  - Smoking cessation among transit workers: beliefs and perceptions among an at-risk
      occupational group.
AB  - BACKGROUND: Transit workers, in comparison to the general population, have higher
      rates of smoking. Although smoking cessation programs are often available through
      workers' HMOs, these programs are frequently underutilized. Quitting practices,
      including participation in cessation programs, are often associated with beliefs
      about smoking behaviors and the ability to quit. We analyzed how transit workers'
      beliefs about cessation might function as barriers to or facilitators of
      participating in cessation activities. FINDINGS: We conducted 11 focus group
      discussions with 71 workers (45% female; 83% African American) at an urban public
      transit agency. Most participants (83%) were bus operators. Only current smokers
      and former smokers were recruited. Both current and former smokers recognized the
      need to quit and some were familiar with or at least aware of cessation programs
      and pharmaceutical aids offered through their HMO. Many, however, believed there
      were factors, such as smoker's readiness to quit, recognition of the elements of
      addiction, and personal or observed experience with cessation, that facilitated
      or impeded successful quit attempts. CONCLUSION: Beliefs play an important role
      and influence the extent to which transit workers participate in smoking
      cessation. Being cognizant of and addressing these beliefs so that workers gain
      an informed understanding is important when designing cessation programs. Doing
      so may help in creating tobacco cessation efforts that are seen as both
      attractive and beneficial to transit workers.

PMID- 25962518
TI  - Current prevalence of Type 1 and Type 2 diabetes in adults and children in the
      UK.

PMID- 25962519
TI  - Erratum: A rare variant in APOC3 is associated with plasma triglyceride and VLDL
      levels in Europeans.

PMID- 25962520
TI  - The limited storage capacity of gonadal adipose tissue directs the development of
      metabolic disorders in male C57Bl/6J mice.
AB  - AIMS/HYPOTHESIS: White adipose tissue (WAT) consists of various depots with
      different adipocyte functionality and immune cell composition. Knowledge of WAT
      depot-specific differences in expandability and immune cell influx during the
      development of obesity is limited, therefore we aimed to characterise different
      WAT depots during the development of obesity in mice. METHODS: Gonadal WAT
      (gWAT), subcutaneous WAT (sWAT) and mesenteric WAT (mWAT) were isolated from male
      C57Bl/6J mice with different body weights (approximately 25-60 g) and analysed.
      Linear and non-linear regression models were used to describe the extent of WAT
      depot expandability and immune cell composition as a function of body weight.
      RESULTS: Whereas mouse sWAT and mWAT continued to expand with body weight, gWAT
      expanded mainly during the initial phase of body weight gain. The expansion
      diminished after the mice reached a body weight of around 40 g. From this point
      on, gWAT crown-like structure formation, liver steatosis and insulin resistance
      occurred. Mouse WAT depots showed major differences in immune cell composition:
      gWAT consisted mainly of macrophages, whereas sWAT and mWAT primarily contained
      lymphocytes. CONCLUSIONS/INTERPRETATION: Marked inter-depot differences exist in
      WAT immune cell composition and expandability. The limited storage capacity of
      gWAT seems to direct the development of metabolic disorders in male C57Bl/6J
      mice.

PMID- 25962521
TI  - Vascular AGE-ing by methylglyoxal: the past, the present and the future.
AB  - Over the years, new research has elucidated the importance of the very fast
      formation of AGEs by the highly reactive methylglyoxal (MGO). It has become clear
      that MGO triggers maladaptive responses in vascular tissue. To counteract the
      deleterious effects of MGO, organisms have an enzymatic glyoxalase defence system
      in which MGO is converted to D-lactate, with glyoxalase 1 (GLO1) as the key
      enzyme in this system. Significant progress has been made towards the
      understanding of the MGO-GLO1 pathway in the pathogenesis of vascular disease in
      diabetes. This commentary highlights some lines of current research and future
      perspectives. The work conducted so far is only the starting point--in the coming
      50 years, the MGO-GLO1 pathway will be the subject of intensified research, with
      special focus on pathophysiological pathways, the use of this system for early
      screening and risk prediction, and the development of intervention strategies for
      preventing vascular complications in people with and without diabetes. This is
      one of a series of commentaries under the banner '50 years forward', giving
      personal opinions on future perspectives in diabetes, to celebrate the 50th
      anniversary of Diabetologia (1965-2015).

PMID- 25962522
TI  - In the patient's shoes.

PMID- 25962523
TI  - Utility of serum free light chain measurements in multiple myeloma patients not
      achieving complete response to therapy.
AB  - Normalization of the serum-free light-chain ratio (FLCr) with the absence of bone
      marrow monoclonal plasma cells following achievement of a complete response (CR)
      to therapy denotes a stringent CR in multiple myeloma (MM), and is associated
      with improved overall survival (OS). However, its value in patients achieving <CR
      is not clear. We hypothesized that patients achieving a normalization of FLCr
      with initial therapy of MM will have an improved outcome, even in the absence of
      a CR. We retrospectively evaluated 449 patients with newly diagnosed MM with
      measurable disease at baseline, who did not achieve a CR with initial therapy.
      One hundred and fifty-three patients (34%) had a normal FLCr, whereas 296 (66%)
      had an abnormal ratio. Patients with a normal FLCr had a longer progression-free
      survival (29 vs 16 months, P<0.001) and OS (91 vs 58 months, P<0.001).
      Normalization of FLCr retained its prognostic value in a multivariable model. Our
      results suggest an important role for sFLC measurement in disease monitoring even
      in patients who achieve only a partial response to therapy. Obtaining a normal
      FLCr confers a favorable prognosis independent from other factors, supporting the
      inclusion of sFLC in all levels of response criteria. 

PMID- 25962525
TI  - Ethnic disparities in thyroid surgery outcomes in New Zealand.
AB  - BACKGROUND: Although thyroid disease is known to have significant ethnic
      variability, ethnic disparities in outcomes of thyroid surgery have been poorly
      studied. METHOD: Retrospective review of 716 consecutive thyroid operations at
      Counties Manukau Health, a public health provider in New Zealand, from January
      2002 to August 2013. RESULTS: Compared with Europeans, Maori and Pacific
      Islanders have longer operation times (P < 0.001) and heavier thyroid glands (P <
      0.001). Polynesians also had higher risk of post-operative haemorrhage compared
      with non-Polynesians (P = 0.016). They also have higher body mass index, American
      Society of Anesthesiologists scores and rates of smoking. There were no
      differences in length of inpatient stay and readmission rates. CONCLUSIONS: There
      are significant ethnic differences in certain outcomes of thyroid surgery. Part
      of this may be explained by higher co-morbid characteristics.

PMID- 25962524
TI  - Toll-like receptor 4 contributes to the inhibitory effect of morphine on colonic
      motility in vitro and in vivo.
AB  - Opioids rank among the most potent analgesic drugs but gastrointestinal side
      effects, especially constipation, limit their therapeutic utility. The adverse
      effects of opioids have been attributed to stimulation of opioid receptors, but
      emerging evidence suggests that opioids interact with the innate immune receptor
      Toll-like receptor 4 (TLR4) and its signalling pathway. As TLR4 signalling
      affects gastrointestinal motility, we examined the involvement of TLR4 in
      morphine-induced depression of peristaltic motility in the guinea-pig intestine
      in vitro and male C57BL/6N mice in vivo. While the TLR4 antagonist TAK-242 (0.1
      MUM and 1 MUM) did not alter the morphine-induced inhibition of peristalsis in
      the isolated guinea-pig small intestine, the morphine-induced decrease in pellet
      propulsion velocity in colonic segments was attenuated by TAK-242 (0.1 MUM). The
      ability of TAK-242 (4 mg/kg) to mitigate the morphine-induced suppression of
      colonic motility was replicated in mice in vivo by measuring the expulsion time
      of beads inserted in the distal colon. The inhibition of upper gastrointestinal
      transit of mice by morphine was not affected by pre-treatment with TAK-242 (4
      mg/kg) in vivo. This is the first report that morphine-induced inhibition of
      colonic peristalsis is alleviated by TLR4 antagonism. We therefore conclude that
      TLR4 may contribute to opioid-induced constipation. 

PMID- 25962526
TI  - Stem cell transplantation before birth - a realistic option for treatment of
      osteogenesis imperfecta?
AB  - Osteogenesis imperfecta (OI) is characterized by severe bone deformities, growth
      retardation and bones that break easily, often from little or no apparent cause.
      OI is a genetic disorder primarily with defective type I collagen with a wide
      spectrum of clinical expression. In the more severe cases, it can be diagnosed
      before birth. Transplantation of mesenchymal stem cells (MSC) has the potential
      to improve the bone structure and stability, growth and fracture healing.
      Prenatal and postnatal cell transplantation has been investigated in preclinical
      and clinical studies of OI and suggests that this procedure is safe and has
      positive effects. Cell transplantation resulted in improved linear growth,
      mobility and reduced fracture incidence. However, the effect is transient and for
      this reason re-transplantation may be needed. So far there is limited experience
      in this area, and proper studies are required to accurately determine if MSC
      transplantation is of clinical benefit in the treatment of OI. In this review, we
      summarize what is currently known in this field.

PMID- 25962527
TI  - Differential mobility spectrometry/mass spectrometry history, theory, design
      optimization, simulations, and applications.
AB  - This review of differential mobility spectrometry focuses primarily on mass
      spectrometry coupling, starting with the history of the development of this
      technique in the Soviet Union. Fundamental principles of the separation process
      are covered, in addition to efforts related to design optimization and
      advancements in computer simulations. The flexibility of differential mobility
      spectrometry design features is explored in detail, particularly with regards to
      separation capability, speed, and ion transmission. 2015 Wiley Periodicals, Inc.
      Mass Spec Rev 35:687-737, 2016.

PMID- 25962528
TI  - Successful haploidentical donor hematopoietic stem cell transplant and
      restoration of STAT3 function in an adolescent with autosomal dominant hyper-IgE
      syndrome.
AB  - PURPOSE: Autosomal dominant hyper-IgE syndrome (AD-HIES), caused by mutations in
      Signal Transducer and Activator of Transcription 3 (STAT3) is associated with
      defective STAT3 signaling and Th17 differentiation and recurrent bacterial and
      fungal infections. Most patients suffer significant morbidity and premature
      mortality. Hematopoietic stem cell transplantation (HSCT) has been reported in a
      small number of cases, with mixed outcomes. We report successful haploidentical
      donor HSCT in a patient with AD-HIES. METHODS: Evaluation of lymphocyte subsets,
      STAT3 signaling, and Th17 cells was performed pre- and post-HSCT. RESULTS: A 14
      year old female with AD-HIES developed recurrent methicillin-resistant
      Staphylococcus aureus (MRSA) abscesses. Immunologic analysis showed elevated IgE
      (4331 kU/L), absent Th17 cells, and markedly decreased STAT3 phosphorylation in
      cytokine stimulated peripheral blood mononuclear cells. She had breakthrough
      abscesses despite clindamycin and trimethoprim-sulfamethoxazole prophylaxis, and
      developed steroid refractory autoimmune hemolytic anemia. She underwent T-cell
      depleted haploidentical HSCT from her father following reduced intensity
      conditioning. She developed one MRSA hand abscess after transplant. Twenty-four
      months post transplant, she had complete donor chimerism (>95 % donor), normal
      absolute T cell numbers, and a normal percentage of Th17 cells. IgE was normal at
      25 kU/L. She remains well 42 months after transplantation off all antibacterial
      prophylaxis. CONCLUSIONS: Haploidentical HSCT led to successful bone marrow
      engraftment, normalization of STAT3 signaling in hematopoietic cells,
      normalization of IgE, and restoration of immune function in this patient with AD
      HIES.

PMID- 25962529
TI  - Analysis of the in vitro nanoparticle-cell interactions via a smoothing-splines
      mixed-effects model.
AB  - A mixed-effects statistical model has been developed to understand the
      nanoparticle (NP)-cell interactions and predict the rate of cellular uptake of
      NPs. NP-cell interactions are crucial for targeted drug delivery systems, cell
      level diagnosis, and cancer treatment. The cellular uptake of NPs depends on the
      size, charge, chemical structure, and concentration of NPs, and the incubation
      time. The vast number of combinations of these variable values disallows a
      comprehensive experimental study of NP-cell interactions. A mathematical model
      can, however, generalize the findings from a limited number of carefully designed
      experiments and can be used for the simulation of NP uptake rates, to design,
      plan, and compare alternative treatment options. We propose a mathematical model
      based on the data obtained from in vitro interactions of NP-healthy cells,
      through experiments conducted at the Nanomedicine and Advanced Technologies
      Research Center in Turkey. The proposed model predicts the cellular uptake rate
      of silica, polymethyl methacrylate, and polylactic acid NPs, given the incubation
      time, size, charge and concentration of NPs. This study implements the mixed
      model methodology in the field of nanomedicine for the first time, and is the
      first mathematical model that predicts the rate of cellular uptake of NPs based
      on sound statistical principles. Our model provides a cost-effective tool for
      researchers developing targeted drug delivery systems. 

PMID- 25962530
TI  - Carotid intima-media thickness measurement promises to improve cardiovascular
      risk evaluation in head and neck cancer patients.
AB  - BACKGROUND: Radiation-treated head and neck cancer (HNC) patients are at high
      risk for developing radiation vasculopathy, as evidenced by an increased stroke
      risk. The benefits of screening and assessing the cardiovascular (CV) risk of HNC
      patients using carotid intima-media thickness (CIMT) ultrasound are not known.
      Our objective was to determine the prevalence of high CV risk in patients without
      known CV diseases who received radiation for HNC, determine the percentage of
      screened patients who had a change in clinical management as a result of an
      increased CIMT, and to compare this risk-assessment tool to patients' risk
      classification using the Framingham Risk Score (FRS) and Pooled Cohort
      Atherosclerotic Cardiovascular Disease (ASCVD) Risk Equation (recommended by
      American College of Cardiology/American Heart Association Guidelines on the
      Assessment of Cardiovascular Risk). HYPOTHESIS: Risk calculators may not
      accurately predict risk in this population with a unique risk factor. Carotid IMT
      may be used to detect radiation vasculopathy in HNC patients. METHODS:
      Retrospective medical chart review was conducted on 134 radiation-treated HNC
      patients. The main outcome measures were CV risk (as determined by CIMT) and
      clinical management. Also, the FRS and the Pooled Cohort ASCVD Risk Equation were
      used to compare classification with CIMT. RESULTS: Approximately 74% of the cases
      were at high CV risk using CIMT technique. Approximately half of the HNC patients
      screened had a change in clinical management characterized by recorded initiation
      of aspirin and recorded initiation or increase of statin therapies. The FRS and
      the Pooled Cohort ASCVD Risk Equation failed to detect 40% to 50% of cases found
      to be at high risk using the CIMT technique. CONCLUSIONS: Carotid IMT identified
      a much greater percentage of radiation-treated HNC patients at high CV risk
      compared with standard CV-risk calculators. By more accurately identifying the
      patients at high risk, this may lead to more effective prevention, and therefore
      a reduction in CV events.

PMID- 25962532
TI  - Highly fluorescent flavins: rational molecular design for quenching protection
      based on repulsive and attractive control of molecular alignment.
AB  - Unprecedented intense fluorescent emission was observed for a variety of flavin
      compounds bearing a perpendicular cyclic imide moiety at the C7 position of an
      isoalloxazine platform. A series of alloxan-substituted flavins was prepared
      selectively by reduction of the corresponding N-aryl-2-nitro-5-alkoxyanilines
      with zinc dust and subsequent reaction with alloxan monohydrate in the presence
      of boric acid. Analogues bearing oxazolidine-2,4-dione functionality were
      obtained on methylation of the alloxan-substituted flavins with methyl iodide and
      subsequent rearrangement in the presence of an inorganic base. The flavin
      compounds exhibit intense white-green fluorescent emission in the solution state
      under UV excitation at 298 K, with emission efficiencies Phi298 K greater than
      0.55 in CH3 CN, which are higher than the values for all reported flavin
      compounds under similar conditions. The highest Phi298 K value of 0.70 was
      obtained in CH3 CN for isoalloxazine bearing C7-alloxan and N10-2,6
      diisopropylphenyl groups. The temperature dependence of the emission intensities
      indicates that the pronounced emission properties at 298 K are attributable to
      the highly heat resistant properties towards emission decay with increasing
      temperature. Mechanistic studies, including X-ray diffraction analysis, revealed
      that the good emission properties and high heat resistance of the alloxan
      substituted flavins are due to a synergetic effect of the associative nature of
      the C7-alloxan unit and the repulsive nature of the perpendicular bulky
      substituents at the C7 and N10 positions. 

PMID- 25962533
TI  - Cardiometabolic risk factors and TV watching in a rural community in West Bengal,
      India.
AB  - BACKGROUND: No study has been undertaken among rural adult population of India to
      investigate the association of cardiometabolic risk factors with TV watching.
      MATERIALS AND METHODS: This cross-sectional study was carried out in 1007
      participants (645 males and 362 females) aged 20-80 years from a rural community.
      Anthropometric measures were collected using standard techniques. HOMA-IR was
      calculated accordingly. RESULTS: The significant higher value for MWC, WHtR, TER,
      SF4, BMI, %BF, FM, VFL, IVF, TC, LDL and FBG was observed with increasing
      duration of TV watching. No significant change was observed for TG, HDL, VLDL,
      DBP and MAP. Chi-square revealed significant difference for central obesity
      between male and females across TV watching category. The higher metabolic
      syndrome phenotypes were prevalent among both sexes with increasing duration of
      TV watching. Furthermore, multiple regression analyses (stepwise) revealed that
      occupation, monthly income, duration of TV watching in a day, education and
      monthly expenditure cumulatively explained ~19% (R(2)=0.191) of the total
      variance of % body fat in the study. CONCLUSION: It seems rational to argue that
      lengthy TV watching time might have detrimental effect on CVD health.

PMID- 25962534
TI  - Improvement of Bovine Nucleus Pulposus Cells Isolation Leads to Identification of
      Three Phenotypically Distinct Cell Subpopulations.
AB  - OBJECTIVE: Strategies to promote intervertebral disc (IVD) regeneration have been
      hindered by the lack of knowledge of IVD fundamental cellular/molecular
      components. One of the key points to be addressed is the characterization of
      nucleus pulposus (NP) cell population(s). This study establishes an improved
      method for bovine NP (bNP) cell isolation, whose procedure is still not
      consensual among the literature, allowing a thorough characterization of cell
      (sub)populations that exist in the young NP. METHODS: bNP was digested with
      distinct enzymes (collagenase-type-I, collagenase-type-II, and collagenase-type
      XI) at different concentrations (0.5, 1.0, and 2.0 mg/mL), for 4 and 19 h. Cell
      yield, viability/apoptosis, and morphology were analyzed by flow cytometry and
      imaging flow cytometry. Identification of cell subpopulations within NP and its
      phenotype was investigated by assessing expression of CD29, CD44, CD45, CD34,
      CD146, and Brachyury. RESULTS: It was found that bNP cells present a similar
      morphology independently of the digestive enzyme used. However, cell yield was
      greatly improved by Coll-XI (2 mg/mL) treatment for a short digestion period.
      Interestingly, three subpopulations, with different sizes and auto-fluorescence,
      were consistently identified by flow cytometry. And crucially, differential
      expression of cell markers was found among these subpopulations. CONCLUSION: This
      study demonstrated that collagenase-type-XI is an efficient enzyme that is used
      for digesting bNP. And most importantly, three phenotypically distinct
      subpopulations of cells where identified within the bNP. Such knowledge is key
      for a better understanding of NP cell biology and its potential endogenous
      regenerative capacity.

PMID- 25962535
TI  - Gold-catalyzed alpha-furanylations of quinoline N-oxides with alkenyldiazo
      carbonyl species.
AB  - Gold-catalyzed alpha-furanylations of 8-alkylquinoline N-oxides have been
      achieved using alkenyldiazo carbonyl species as nucleophiles. The reactions are
      applicable to a reasonable range of alkenyldiazo species and 8-alkylquinoline N
      oxides. The reaction mechanism is postulated to involve an initial nucleophilic
      addition of diazocarbonyl species at 8-alkylquinoline N-oxides, followed by diazo
      decomposition. 

PMID- 25962536
TI  - Development of a duplex one-step RT-qPCR assay for the simultaneous detection of
      Apple scar skin viroid and plant RNA internal control.
AB  - Apple scar skin viroid (ASSVd) is an important quarantine pathogen for
      international movement of pome germplasm as it can cause significant damage to
      pip fruit. A one-step real-time RT-PCR assay was developed for the rapid and
      sensitive detection of ASSVd. The assay was able to detect a wide range of ASSVd
      isolates and was highly specific compared to a published conventional RT-PCR. The
      detection limit of the new assay was estimated to be about 100 copies of the
      ASSVd target. The assay can be run as a duplex with the nad5 internal control
      primers and probe to simultaneously check the PCR competency of the samples
      therefore reducing the risk of false negatives. It is expected that this real
      time RT-PCR assay will facilitate efficient testing for ASSVd by regulatory
      services, and will also have a wider use for the general detection of ASSVd in a
      range of pip fruit. 

PMID- 25962537
TI  - A multiplex RT-PCR assay for the detection of fish picornaviruses.
AB  - With the emergence of high profile fish diseases in the Great Lakes region,
      surveillance and regulatory inspections of fish populations have increased. This
      has resulted in a better understanding of known pathogens and isolation of many
      new pathogens of fish. In this study, a multiplex RT-PCR assay was developed for
      the detection of three newly discovered fish picornaviruses: bluegill
      picornavirus-1 (BGPV-1), fathead minnow picornavirus (FHMPV), and eel
      picornavirus-1 (EPV-1). This assay was found to be very sensitive with a
      detection limit of 81.9pg/MUl of extracted RNA from a pool of FHMPV and BGPV-1
      and was able to detect 501 and 224 gene copies/MUl of BGPV-1 and FHMPV,
      respectively. The assay was highly reproducible and did not cross react with
      other closely related pathogens. We believe that this new assay provides a rapid
      and cost effective tool for confirming cell culture isolates and conducting
      prevalence studies of these newly detected fish picornaviruses. 

PMID- 25962538
TI  - Molecular analyses detect natural coinfection of water buffaloes (Bubalus
      bubalis) with bovine viral diarrhea viruses (BVDV) in serologically negative
      animals.
AB  - Infection of water buffaloes (Bubalus bubalis) with bovine viral diarrhea viruses
      (BVDV) has been confirmed in several studies by serological and molecular
      techniques. In order to determine the presence of persistently infected animals
      and circulating species and subtypes of BVDV we conducted this study on a buffalo
      herd, whose habitat was shared with bovine cattle (Bossp.). Our serological
      results showed a high level of positivity for BVDV-1 and BVDV-2 within the
      buffalo herd. The molecular analyses of blood samples in serologically negative
      animals revealed the presence of viral nucleic acid, confirming the existence of
      persistent infection in the buffaloes. Cloning and sequencing of the 5' UTR of
      some of these samples revealed the presence of naturally mix-infected buffaloes
      with at least two different subtypes (1a and 1b), and also with both BVDV species
      (BVDV-1 and BVDV-2). 

PMID- 25962539
TI  - [Bovine herpesvirus 4 (BoHV-4): general aspects of the biology and status in
      Argentina].
AB  - Bovine herpesvirus 4 (BoHV-4) has been isolated from cattle with respiratory
      infections, vulvovaginitis, mastitis, abortions, endometritis and from apparently
      healthy animals throughout the world. Although it has not yet been established as
      causal agent of a specific disease entity, it is primarily associated with
      reproductive disorders of cattle. This virus can infect a wide range of species,
      either in vivo or in vitro. Two groups of prototype strains were originated from
      the first isolates: the DN599-type strains (American group) and the Movar-type
      strains (European group). In Argentina, BoHV-4 was isolated and characterized in
      2007 from vaginal discharge samples taken from cows that had aborted. So far,
      more than 40 isolates, mainly associated with aborting bovine females have been
      registered in our country. 

PMID- 25962540
TI  - Precise Actuation of Bilayer Photomechanical Films Coated with Molecular
      Azobenzene Chromophores.
AB  - Bilayer photomechanical films are fabricated by depositing one layer of molecular
      azobenzene chromophores onto flexible low-density polyethylene substrates. The
      photoinduced bending and unbending behavior of five azobenzene derivatives
      including azobenzene, 4-hydroxy-azobenzene, 4-((4
      hydroxyphenyl)diazenyl)bezoitrile, 4-((4-methoxyph-enyl)diazenyl)phenol, and 4
      (phenyldiazenyl)phenol is systematically studied by considering the incident
      light intensity and the thickness of the coated chromophore layers. Precise
      control of photoinduced curling of the bilayer film is successfully achieved upon
      irradiation with two beams of UV light, and the curled films can be recovered by
      thermal relaxation in the dark. The easily fabricated bilayer films show fast
      photomechanical response, strong photoinduced stress, and stability similar to
      crosslinked polymeric films. 

PMID- 25962541
TI  - [Post-hematopietic stem cell transplant complications].
AB  - Under the long-term monitoring of patients treated in childhood or adolescence
      for cancer, we present in this article the long-term monitoring and therefore
      possible effects of patients who underwent allergenic hematopoietic stem cell
      transplantation. This article is based on a collaborative effort organized by the
      French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC), which
      took place during the 4th day of allograft harmonization practices. Patients
      affected are children and young adults (0-25 years). We defined the monitoring
      effects beyond 1 year post-transplant. Our recommendations are based on a
      literature review, in line with the Leucemie Enfant Adulte (LEA) study cohort of
      long-term monitoring of patients treated for hematological malignancies in
      childhood, grafted or not. It became important to determine the nature of
      problems, their risk factors, frequency and monitoring necessary to implement for
      their detection. We will not address the therapeutic management of sequelae.

PMID- 25962542
TI  - [Neurosensory, aesthetic and dental late effects of childhood cancer therapy].
AB  - Oncologic management in pediatric patient may be associated with a high risk of
      neurosensory deficit, such as taste, olfaction, vision and hearing. These
      neurosensory deficits can be linked to chemotherapy toxicity or to a direct
      deleterious effect of local radiotherapy or surgical management in case of
      craniofacial cancers. Neurosensory deficit may be temporary but are usually
      irreversible and frequently progress after the completion of treatment. Taste and
      olfaction deficits expose to high risk of nutritional complications and quality
      of life alteration. Hyposialia, as a result of irradiation of the salivary
      glands, increases taste changes and the risk of dental caries. The risk of
      cataract is present in patients who received high dose corticosteroids and/or
      brain or orbital irradiation. When hearing is affected, a risk of impaired
      intellectual or academic performance is increased with an impact on the quality
      of life in absence of specific care. Finally, there are some cosmetic
      consequences of therapy such as alopecia and scarring that alter the image of the
      patient. Early detection of these problems in order to limit medical,
      psychological, educational and social impact is mandatory. Moreover, high risk of
      worsening of these deficits after completion of therapy support long-term follow
      up children treated for cancer, especially with head and neck primary. 

PMID- 25962543
TI  - Chronic Pain and Decreased Opioid Efficacy: An Inflammatory Link.
AB  - Chronic pain is a devastating amalgam of symptoms that affects millions of
      Americans at tremendous cost to our healthcare system and, more importantly, to
      patients' quality of life. Literature and research demonstrate that neuroimmune
      cells called glia are not only responsible for initiating and maintaining part of
      the chronic pain disease process, but also release inflammatory molecules
      responsible for decreasing the efficacy of one of the most prominent treatments
      for pain, opioid analgesia. This article describes chronic pain as a disease
      process that has ineffective treatment modalities, explores the mechanisms of
      glial cell activation and inflammatory responses that lead to chronic pain and
      decreased opioid treatment efficacy, and hypothesizes novel chronic pain
      treatment modalities based on the glial cell inactivation and anti-inflammatory
      pathways. 

PMID- 25962544
TI  - Validity, Sensitivity, and Responsiveness of the 11-Face Faces Pain Scale to
      Postoperative Pain in Adult Orthopedic Surgery Patients.
AB  - Pain is common in patients after orthopedic surgery. The 11-face Faces Pain Scale
      has not been validated for use in adult patients with postoperative pain. To
      assess the validity of the 11-face Faces Pain Scale and its ability to detect
      responses to pain medications, and to determine whether the sensitivity of the 11
      face Faces Pain Scale for detecting changes in pain intensity over time is
      associated with gender differences in adult postorthopedic surgery patients. The
      11-face Faces Pain Scale was translated into Vietnamese using forward and back
      translation. Postoperative pain was assessed using an 11-point numerical rating
      scale and the 11-face Faces Pain Scale on the day of surgery, and before (Time 1)
      and every 30 minutes after (Times 2-5) the patients had taken pain medications on
      the first postoperative day. The 11-face Faces Pain Scale highly correlated with
      the numerical rating scale (r = 0.78, p < .001). When the scores from each follow
      up test (Times 2-5) were compared with those from the baseline test (Time 1), the
      effect sizes were -0.70, -1.05, -1.20, and -1.31, and the standardized response
      means were -1.17, -1.59, -1.66, and -1.82, respectively. The mean change in pain
      intensity, but not gender-time interaction effect, over the five time points was
      significant (F = 182.03, p < .001). Our results support that the 11-face Faces
      Pain Scale is appropriate for measuring acute postoperative pain in adults. 

PMID- 25962545
TI  - A Comprehensive Review of Central Post-Stroke Pain.
AB  - Although central post-stroke pain is widely recognized as a severe chronic
      neuropathic pain condition, its consolidated definition, clinical
      characteristics, and diagnostic criteria have not been defined due to its
      clinically diverse features. The present study was undertaken to comprehensively
      review current literature and provide a more complete picture of central post
      stroke pain with respect to its definition, prevalence, pathophysiology, clinical
      characteristics, and diagnostic problems, and to describe the range of therapies
      currently available. In particular, nursing care perspectives are addressed. It
      is hoped that this review will help nurses become knowledgeable about central
      post-stroke pain and provide valuable information for the drafting of effective
      nursing care plans that improve outcomes and quality of life for patients with
      central post-stroke pain. 

PMID- 25962546
TI  - Ethnic Differences in Nonverbal Pain Behaviors Observed in Older Adults with
      Dementia.
AB  - Research supports using nonverbal pain behaviors to identify pain in persons with
      dementia. It is unknown whether variations exist among ethnic groups in the
      expression of nonverbal pain behaviors in this special population. The purpose of
      this descriptive study was to examine ethnic differences in the presentation and
      intensity of nonverbal pain behaviors among African American, Caucasian, and
      Hispanic older adults with dementia when screened for pain by certified nursing
      assistants. Six certified nursing assistants were trained to review and score 28
      video recordings of subjects with dementia for nonverbal pain behaviors using the
      Non-Communicative Patient's Pain Assessment Instrument. Chi-square was used to
      examine differences among ethnic groups with regard to the display of nonverbal
      pain behaviors, and ANOVA was used to evaluate differences in the intensity of
      overall pain across ethnic groups. Of the 168 assessments, pain words (28%), pain
      noises (29.8%), and pain faces (28%) were observed most often as indicators of
      pain. Rubbing, bracing, and restlessness were rarely noted. Chi-square analysis
      revealed ethnic differences in the expression of pain words (chi(2) = 19.167, p <
      .001). No significant differences were noted across ethnic groups with regards to
      overall pain intensity. These findings are the first to examine ethnic
      differences in nonverbal pain behaviors for older adults with dementia. However,
      future work should examine assessment tendencies of providers in a larger, more
      diverse sample. 

PMID- 25962547
TI  - Evaluation and Treatment of Penile Thrombophlebitis (Mondor's Disease).
AB  - Superficial penile thrombophlebitis or penile Mondor's disease (PMD) is an
      underreported condition that causes anxiety and embarrassment in affected men.
      Patients usually present with a smooth, cord-like induration on the dorsal penile
      shaft 1-7 days after prolonged or intensive sexual intercourse, but other
      presentations of disease and triggers for endothelial damage are possible. The
      condition is typically self-limited with expected spontaneous resolution within 4
      8 weeks of initial presentation, and absolute diagnosis is usually not necessary
      with management including supportive care and pain control. However, when disease
      course is prolonged or there are concerning risk factors, it may be important to
      differentiate PMD from other conditions such as Peyronie's disease,
      hypercoagulability, blood stasis, genitourinary infection, and malignancy.
      History and physical are often sufficient to distinguish these conditions from
      PMD, but providers may employ ultrasound to assist with the diagnosis. If PMD
      does not spontaneously resolve, patients may be considered for thrombectomy, at
      which point histological analysis can confirm the diagnosis.

PMID- 25962548
TI  - The significance of cooking for early hominin scavenging.
AB  - Meat scavenged by early Homo could have contributed importantly to a higher
      quality diet. However, it has been suggested that because carrion would normally
      have been contaminated by bacteria it would have been dangerous and therefore
      eaten rarely prior to the advent of cooking. In this study, we quantified
      bacterial loads on two tissues apparently eaten by hominins, meat and bone
      marrow. We tested the following three hypotheses: (1) the bacterial loads on
      exposed surfaces of raw meat increase within 24 h to potentially dangerous
      levels, (2) simple roasting of meat on hot coals kills most bacteria, and (3)
      fewer bacteria grow on marrow than on meat, making marrow a relatively safe food.
      Our results supported all three hypotheses. Our experimental data imply that
      early hominins would have found it difficult to scavenge safely without focusing
      on marrow, employing strategies of carrion selection to minimize pathogen load,
      or cooking.

PMID- 25962549
TI  - A systematic revision of Proconsul with the description of a new genus of early
      Miocene hominoid.
AB  - For more than 80 years, Proconsul has held a pivotal position in interpretations
      of catarrhine evolution and hominoid diversification in East Africa. The majority
      of what we 'know' about Proconsul, however, derives from abundant younger fossils
      found at the Kisingiri localities on Rusinga and Mfangano Islands rather than
      from the smaller samples found at Koru--the locality of the type species,
      Proconsul africanus--and other Tinderet deposits. One outcome of this is seen in
      recent attempts to expand the genus "Ugandapithecus" (considered here a junior
      subjective synonym of Proconsul), wherein much of the Tinderet sample was
      referred to that genus based primarily on differentiating it from the Kisingiri
      specimens rather than from the type species, P. africanus. This and other recent
      taxonomic revisions to Proconsul prompted us to undertake a systematic review of
      dentognathic specimens attributed to this taxon. Results of our study underscore
      and extend the substantive distinction of Tinderet and Ugandan Proconsul (i.e.,
      Proconsul sensu stricto) from the Kisingiri fossils, the latter recognized here
      as a new genus. Specimens of the new genus are readily distinguished from
      Proconsul sensu stricto by morphology preserved in the P. africanus holotype, but
      also in I(1)s, lower incisors, upper and lower canines, and especially mandibular
      characteristics. A number of these differences are more advanced among Kisingiri
      specimens in the direction of crown hominoids. Proconsul sensu stricto is
      characterized by a suite of unique features that strongly unite the included
      species as a clade. There have been decades of contentious debate over the
      phylogenetic placement of Proconsul (sensu lato), due in part to there being a
      mixture of primitive and more advanced morphology within the single genus. By
      recognizing two distinct clades that, in large part, segregate these character
      states, we believe that better phylogenetic resolution can be achieved.

PMID- 25962550
TI  - Giant African pouched rats (Cricetomys gambianus) that work on tilled soil
      accurately detect land mines.
AB  - Pouched rats were employed as mine-detection animals in a quality-control
      application where they searched for mines in areas previously processed by a
      mechanical tiller. The rats located 58 mines and fragments in this 28,050-m(2)
      area with a false indication rate of 0.4 responses per 100 m(2) . Humans with
      metal detectors found no mines that were not located by the rats. These findings
      indicate that pouched rats can accurately detect land mines in disturbed soil and
      suggest that they can play multiple roles in humanitarian demining. 

PMID- 25962551
TI  - C19orf12 gene mutations in patients with neurodegeneration with brain iron
      accumulation.
AB  - A novel subtype of Neurodegeneration with Brain Iron Accumulation (NBIA) recently
      has been described: mitochondrial membrane protein-associated neurodegeneration
      (MPAN), caused by mutations of c19orf12 gene. We present phenotypic data and
      results of screening of C19orf12 in five unrelated NBIA families. Our data led to
      identify novel pathogenic mutations in C19orf12. 

PMID- 25962552
TI  - Impaired heart rate variability in patients with dementia with Lewy bodies:
      Efficacy of electrocardiogram as a supporting diagnostic marker.
AB  - OBJECTIVE: It has been suggested that impaired heart rate variability (HRV) may
      be an early sign of Parkinson's disease (PD). The aim of this study was to
      determine whether HRV can be employed in order to differentiate between dementia
      with Lewy bodies (DLB) and Alzheimer's disease (AD). METHODS: We examined HRV in
      30 probable DLB patients (16 men and 14 women; mean age, 79.9 years; SD, 4.7
      years), and 30 probable AD patients (15 men and 15 women; mean age, 79.8 years;
      SD, 5.6 years), compared with that in 20 age- and sex-matched controls. Subjects
      with other causes of impaired HRV were excluded. HRV was determined using the RR
      intervals of a 5-min electrocardiogram recording. Measurements of beat-to-beat RR
      variability, including time domains [(RR-standard deviation (SDNN), percentage of
      consecutive RR intervals differing by more than 50 msec (pNN50), and root mean
      square difference of successive RR intervals (RMSSD)), and frequency domains
      [very low- (VLF), low- (LF), and high-frequency (HF) components, and total
      spectral power (Total power)], were assessed retrospectively. The association
      between these HRV parameters and cardiac iodine-123 metaiodobenzylguanidine
      ((123)I-MIBG) scintigraphy were investigated in 22 probable DLB patients.
      RESULTS: DLB group showed significant decreases compared to AD group in almost
      all HRV parameters including SDNN, pNN50, RMSSD, VLF, LF, HF, and Total power.
      Among these, SDNN, VLF, and Total power were correlated with the (123)I-MIBG
      delayed heart to mediastinum ratio. CONCLUSION: Impaired HRV was detected in
      patients with probable DLB. Non-invasive and routine electrocardiogram may have
      potential in differentiating DLB from AD.

PMID- 25962553
TI  - LRRK2 mutations in Parkinson disease; a sex effect or lack thereof? A meta
      analysis.
AB  - BACKGROUND: It is currently under debate whether there is a sex effect in LRRK2
      associated Parkinson disease (PD), as several studies suggested such effect while
      others did not. METHODS: All case-control studies describing LRRK2 mutations and
      PD were examined, and papers with data on sex and LRRK2 mutations in both
      patients and controls were included (n = 17) in a sex-stratified meta-analysis.
      Additional studies (n = 33) that included data on male:female ratio only in
      patients with LRRK2 mutations, were included in further analysis of male:female
      ratio in LRRK2-assocoiated PD patients. RESULTS: Similar risk estimates were
      calculated for men and women. Among men, LRRK2 mutation carriers had a pooled OR
      for PD of 4.20 (95% CI 2.95-5.99, p < 0.0001) and among women, LRRK2 mutation
      carriers had a pooled OR for PD of 4.73 (95% CI 3.26-6.86, p < 0.0001). Similar
      risk estimates for men and women were also observed when analysing specific LRRK2
      mutations. A total of 1080 LRRK2-associated PD patients with sex information were
      identified. The male:female ratio was 1.02:1.00 (50.6% men and 49.4% women).
      CONCLUSION: While sporadic PD is characterized by a sex effect, with more
      affected men than women, LRRK2-associated PD lacks a sex effect, as typically
      seen in autosomal dominant traits.

PMID- 25962554
TI  - Initiation and dose optimization for levodopa-carbidopa intestinal gel: Insights
      from phase 3 clinical trials.
AB  - BACKGROUND: Levodopa-carbidopa intestinal gel (LCIG) provides continuous infusion
      and reduces "off" time in advanced Parkinson's disease (PD) patients with motor
      fluctuations despite optimized pharmacotherapy. METHODS: Clinical experience with
      2 LCIG dosing paradigms from phase 3 studies was examined. In an open-label, 54
      week study, LCIG was initiated as daytime monotherapy via nasojejunal (NJ) tube
      then switched to percutaneous endoscopic gastrojejunostomy (PEG-J) tube;
      adjunctive therapy was permitted 28 days postPEG-J. In a 12-week, double-blind,
      placebo-controlled, double-dummy trial, patients continued stable doses of
      existing anti-PD medications, but LCIG replaced daytime oral levodopa-carbidopa
      and was initiated directly via PEG-J. RESULTS: In the open-label study, 92% of
      354 patients received monotherapy at post-PEG-J week 4; mean titration duration
      was 7.6 days; dosing remained stable post-titration (mean total daily dose [TDD]
      was 1572 mg at last visit). In the double-blind trial, 84% received polypharmacy;
      mean titration took 7.1 days for the LCIG arm (TDD post-titration: 1181 mg; n =
      37). At post-PEG-J week 4, mean "off" time with LCIG was reduced by 3.9 h (open
      label/monotherapy study) and 3.7 h (double-blind/polypharmacy trial). NJ
      treatment (open-label study only) required an additional procedure with related
      adverse events (AEs) and withdrawals. The most common AEs during PEG-J weeks 1-4
      in the open-label/monotherapy and double-blind/polypharmacy trials, respectively,
      were complication of device insertion (35%, 57%) and abdominal pain (26%, 51%).
      Discontinuations due to nonprocedure/nondevice AEs were low (2.2%, 2.7%).
      CONCLUSION: These results support the option of initiating LCIG with or without
      NJ and as either monotherapy or polypharmacy.

PMID- 25962555
TI  - Surgical embolectomy for internal carotid artery terminus occlusion.
AB  - The aim of this study was to assess the efficacy and safety of surgical
      embolectomy for internal carotid artery terminus (ICA-T) occlusion. Twenty-five
      consecutive patients with acute ischemic stroke attributed to embolic ICA-T
      occlusion who underwent surgical embolectomy were retrospectively reviewed.
      Twenty-four patients were examined based on magnetic resonance imaging, with one
      patient included based on a computed tomography scan. Recanalization rate,
      recanalization time, complications, National Institutes of Health Stroke Scale
      (NIHSS) score improvement at 1 month, and modified Rankin Scale (mRS) at 3 months
      were evaluated. Final recanalization status was Thrombolysis in Myocardial
      Infarction (TIMI) 3 in 24 patients (96 %). Median recanalization time from
      symptom onset and from start of surgery was 281 and 79 min, respectively. Two
      patients (8 %) had major hemorrhagic complications related to surgery. Seventeen
      patients (68 %) demonstrated NIHSS score improvement of more than 10 points at 1
      month. At 3 months, eight patients (32 %) were mRS 0-2, five patients (20 %) were
      mRS 3, and three patients (12 %) had died. Surgical embolectomy for ICA-T
      occlusion demonstrated a high complete recanalization rate and should be
      reconsidered as an additional therapeutic strategy to overcome this devastating
      situation. 

PMID- 25962556
TI  - Treatment outcomes of surgical clipping for unruptured anterior circulation
      aneurysm-single institute experiences in the era of neurophysiologic monitoring
      and endovascular treatment.
AB  - Recently, the treatment of intracranial aneurysms entered a new phase due to safe
      surgical tool such as neurophysiologic monitoring and challenged by endovascular
      treatment. To determine the safety of clipping surgery in the modern era, we
      reviewed our experiences of simple unruptured anterior circulation aneurysm
      surgery which is commonly performed in many places. We retrospectively reviewed
      610 consecutive patients who were treated with surgical clipping under motor
      evoked potential (MEP) monitoring for a tiny to large anterior circulation
      aneurysm in a single institute between 2008 and 2012. MEP changes were identified
      in 40 cases (6.6 %). MEP deterioration was associated with remote site epidural
      hematoma (n = 1), anesthesia (n = 2), temporary clipping (n = 21), and permanent
      clipping (n = 16). Despite that no persistent MEP deterioration was noted after
      prompt corrective measures, 56 (9.2 %) patients showed symptomatic (n = 14) and
      asymptomatic (n = 42) radiologic abnormalities. Anterior cerebral artery (ACA)
      aneurysm was associated with a higher radiologic complication rate (Fisher's
      exact test, P < 0.05). Two (0.3 %) patients showed severe morbidity (mRS >2) at
      latest follow-up. MEP monitoring can be helpful in preventing postoperative motor
      deterioration but seems to have some limitations. Although the permanent
      morbidity rate was low, a significant clinical (2.3 %) or radiologic (9.2 %)
      abnormality rate was identified even in simple aneurysm clipping that should be
      taken into account when performing interdisciplinary treatment planning and
      patient counseling. Also, direct vascular monitoring or new neurophysiologic
      monitoring techniques are needed to reduce surgical complications, especially in
      ACA aneurysm surgery. 

PMID- 25962557
TI  - Assessment of a method to determine deep brain stimulation targets using
      deterministic tractography in a navigation system.
AB  - Recent advances in imaging permit radiologic identification of target structures
      for deep brain stimulation (DBS) for movement disorders. However, these methods
      cannot detect the internal subdivision and thus cannot determine the appropriate
      DBS target located within those subdivisions. The aim of this study is to provide
      a straightforward method to obtain an optimized target (OT) within DBS target
      nuclei using a widely available navigation system. We used T1- and T2-weighted
      images, fluid-attenuated inversion recovery (FLAIR) sequence, and diffusion
      tensor imaging (DTI) of nine patients operated for DBS in our center. Using the
      StealthViz(r) software, we segmented the targeted deep structures (subcortical
      targets) and the anatomically identifiable areas to which these target nuclei
      were connected (projection areas). We generated fiber tracts from the projection
      areas. By identifying their intersections with the subcortical targets, we
      obtained an OT within the DBS target nuclei. We computed the distances from the
      clinically effective electrode contacts (CEEC) to the OT obtained by our method
      and the targets provided by the atlas. These distances were compared using a
      Wilcoxon signed-rank test, with p < 0.05 considered statistically significant. We
      were able to identify OT coincident with the motor part of the subthalamic
      nucleus and the ventral intermediate nucleus. We clinically tested the results
      and found that the CEEC were significantly more closely related to the OT than
      with the targets obtained by the atlas. Our present results show that this novel
      method permits optimization of the stimulation site within the internal
      subdivisions of target nuclei for DBS. 

PMID- 25962559
TI  - The brain of STEMI.

PMID- 25962560
TI  - An unusual emphysema.

PMID- 25962558
TI  - Hyperglycemia management in patients admitted to internal medicine in Spain: A
      point-prevalence survey examining adequacy of glycemic control and guideline
      adherence.
AB  - AIMS: Despite the increasing prevalence of hospitalized diabetic patients, there
      are few studies that evaluate the glycemic control and the rate of adherence to
      clinical practice guidelines for glucose monitoring and management in the
      hospital setting. METHODS: Crossover study using one-day surveys of all
      inpatients admitted to internal medicine wards from voluntary participating
      hospitals across Spain. Retrospective review of medical records was used to
      identify patients with hyperglycemia, causes for hospitalization, patients'
      demographic characteristics, appropriateness of glycemic monitoring and treatment
      during hospitalization. RESULTS: Among 5439 hospitalized patients studied there
      were 1000 (18.4%) with hyperglycemia in 111 participating hospitals. Patients
      mean age was 76.0+/-8.5 years (51.6% male). On admission, 91% had known diabetes
      (disease duration of 10.9+/-8.5 years), 5% had unknown diabetes and 4% had stress
      hyperglycemia. The comorbidity index (Charslon score) was 4 (interquartile range:
      2 to 6) and 31% showed a high level of disability (Rankin scale). Main
      infringement in the process of care included lack of a recent HbA1c value
      (43.7%), use of sliding scale insulin therapy (20.7%), use of oral antidiabetic
      agents (8.9%), and less than three bedside point-of-care (POC) blood glucose test
      per day (17%). Glycemic target pre-meal and bedtime were achieved in 47% to 79.5%
      of POC. The rates of hypoglycemia (<70 mg/dL and <50mg/dL) were 10.3% and 2.4%,
      respectively. CONCLUSIONS: Our results suggest that there is an important gap
      between the clinical guidelines and both the management and the grade of glycemic
      control of diabetic inpatients.

PMID- 25962561
TI  - Bullying Victimization, Parenting Stress, and Anxiety among Adolescents and Young
      Adults with Autism Spectrum Disorder.
AB  - Bullying victimization is commonly associated with anxiety among individuals with
      and without Autism Spectrum Disorder (ASD), and both bullying victimization and
      anxiety are more prevalent among youth with ASD than in the general population.
      We explored individual and contextual factors that relate to anxiety in
      adolescents and young adults with ASD who also experience bullying victimization.
      Participants included 101 mothers of adolescents and young adults diagnosed with
      ASD. Hierarchical multiple regression analyses were conducted to investigate the
      relationship between bullying victimization and anxiety in children with ASD, as
      well as parenting stress as a potential moderator of that relationship. Findings
      indicate that parenting stress moderates the association between bullying
      victimization and anxiety. The severity of anxiety was most strongly associated
      with bullying victimization when mothers reported high levels of stress.
      Implications for interventions that assist parents with coping and address
      bullying victimization are discussed.

PMID- 25962562
TI  - Suppression of phosphatase and tensin homolog protects insulin-resistant cells
      from apoptosis.
AB  - In the present study, a glucosamine-induced model of insulin-resistant skeletal
      muscle cells was established in order to investigate the effect of inhibition of
      phosphatase and tensin homolog (PTEN)/5'-adenosine monophosphate-activated
      protein kinase (AMPK) on these cells. The glucosamine-induced insulin-resistant
      skeletal muscle cells were produced and the rate of glucose uptake was measured
      using the glucose oxidase-peroxidase method. The expression levels of PTEN and
      phosphorylated PTEN (p-PTEN) were assessed using western blotting. Glucose
      transporter 4 (GLUT4) translocation was detected by immunofluorescence. Cell
      apoptosis was evaluated using flow cytometry. Following insulin stimulation, the
      rate of glucose uptake was significantly reduced in the cells with glucosamine
      induced insulin-resistance in comparison with those in the control group. The
      expression and translocation of GLUT4 were reduced in the insulin-resistant
      muscle cells. By contrast, the expression of PTEN and p-PTEN as well as apoptosis
      were significantly increased. Following treatment with
      bisperoxopicolinatooxovanadate (BPV) or metformin in the insulin-resistant
      skeletal muscle cells, there was an increase in the rate of glucose uptake, an
      increase in GLUT4 expression and its translocation, a reduction in the expression
      of PTEN and p-PTEN, and a decrease in cell apoptosis compared with untreated
      insulin-resistant cells. Glucosamine may be used to produce an effective model of
      insulin-resistant skeletal muscle cells. Cells with glucosamine-induced insulin
      resistance exhibited a reduced expression of GLUT4 and dysfunction in GLUT4
      translocation, as well as increased activation of PTEN and increased cell
      apoptosis. Inhibition of PTEN or its upstream regulator, AMPK, protects
      glucosamine-induced insulin-resistant skeletal muscle cells from apoptosis.

PMID- 25962565
TI  - Towards parallel fabrication of single electron transistors using carbon
      nanotubes.
AB  - Single electron transistors (SETs) are considered to be promising building blocks
      for post CMOS era electronic devices, however, a major bottleneck for practical
      realization of SET based devices is a lack of a parallel fabrication approach.
      Here, we have demonstrated a technique for the scalable fabrication of SETs using
      single-walled carbon nanotubes (SWNTs). The approach is based on the integration
      of solution processed individual SWNTs via dielectrophoresis (DEP) at the
      selected position of the circuit with a 100 nm channel length, where the metal
      SWNT Schottky contact works as a tunnel barrier. Measurements carried out at a
      low temperature (4.2 K) show that the majority of the devices with a contact
      resistance (RT) > 100 kOmega display SET behavior. For the devices with 100
      kOmega < RT < 1 MOmega, periodic, well-defined Coulomb diamonds with a charging
      energy of ~14 meV, corresponding to the transport through a single quantum dot
      (QD) was observed. For devices with high RT (>1 MOmega) multiple QD behavior was
      observed. From the transport study of 50 SWNT devices, a total of 38 devices show
      SET behavior giving a yield of 76%. The results presented here are a significant
      step forward for the practical realization of SET based devices. 

PMID- 25962563
TI  - The Benefits of Authorized Agent Controlled Analgesia (AACA) to Control Pain and
      Other Symptoms at the End of Life.
AB  - CONTEXT: Eliza Coffee Memorial Hospital is a community hospital with a palliative
      care unit providing inpatient symptom management and end-of-life care. The
      palliative care unit provides authorized agent controlled analgesia (AACA).
      OBJECTIVES: The objective of this study was to determine if an AACA system
      improves control of pain and other end-of-life symptoms adequately and if it
      provides families with satisfactory involvement in the care of their loved ones.
      METHODS: Data on demographics, pain assessments, length of stay before and after
      consult, drugs used, mortality, discharge disposition, and family and staff
      satisfaction were collected by chart review of all 2013 consultations. RESULTS:
      There was a total of 318 consults in 2013. Of the 118 patients (37% of total) who
      used the AACA system, 112 (95%) died in hospital; morphine was used by 77% and
      the others used hydromorphone. Following the patient's death, of the 70 AACA
      families contacted, 100% were satisfied with the pain/symptom control. Staff also
      were overwhelmingly pleased with the system. CONCLUSION: An AACA system has been
      highly satisfactory for patients, families, and staff, meeting the goals of 1)
      allowing patients with a terminal condition to die peacefully and 2) enabling
      families to share in the patients' care, providing them with a more favorable
      memory at the end of life.

PMID- 25962564
TI  - The Evaluation of Antioxidant Interactions among 4 Common Vegetables using
      Isobolographic Analysis.
AB  - Isobolographic analysis was used to assess the antioxidant interactions
      (synergism, addition, and antagonism) of 4 common vegetables (tomato [T], carrot
      [C], eggplant [E], and purple potato [P]). The lipophilic (L) extracts of T and C
      (main carotenoids), the hydrophilic (H) extracts of E and P (main phenolics) were
      mixed by the certain ratios (1:9, 3:7, 1:1, 7:3, 9:1, w/w) and their antioxidant
      activities were investigated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'
      Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) radical scavenging assays,
      respectively. Most of the binary mixtures (LC-HE, LC-HP, HE-HP, LT-HE, and LT-HP
      combinations) showed the synergistic antioxidant effects. In DPPH assay, the
      greatest antioxidant activity of vegetable combinations was 1:9 LT-HP (EC50 :
      2.45 +/- 0.13 mg/mL), followed by 9:1 HE-HP (EC50 : 3.62 +/- 0.12 mg/mL) and 1:9
      LC-HE (EC50 : 3.74 +/- 0.47 mg/mL). In ABTS assay, the greatest antioxidant
      activity of vegetable combinations was 9:1 HE-HP (EC50 : 4.20 +/- 0.10 mg/mL),
      followed by 7:3 HE-HP (EC50 : 4.41 +/- 0.63 mg/mL) and 1:1 HE-HP (EC50 : 5.35 +/-
      0.85 mg/mL). Among these combinations, 1:1 LC-HE combination showed the highest
      synergistic antioxidant effects in DPPH assay (synergistic rate: 87.4%), and 7:3
      LC-HE combination showed the highest synergistic antioxidant effects in ABTS
      assay (synergistic rate: 87.0%). The mixtures of phenolics and carotenoids with
      suitable ratios in vegetables effectively enhanced the synergistic antioxidant
      effects. 

PMID- 25962566
TI  - Biological actions of pentraxins.
AB  - The innate immunity is the first defense reaction against microorganisms or
      altered self-components upon tissue injury. Such exogenous or modified endogenous
      molecules present conserved molecular structures that are recognized by the
      immune system via pattern-recognition receptors or molecules. Within the soluble
      pattern-recognition molecules pentraxins play an important role in humoral innate
      immunity. Pentraxins branch off into the short and long pentraxins. Short
      constituents include C-reactive protein (CRP) and serum amyloid P-component which
      are synthesized in the liver mostly upon IL-6 stimulation. Long constituent
      pentraxin3 (PTX3) is produced by several immune and vascular cells in response to
      pro-inflammatory signals (but not IL-6) and by toll-like receptor engagement. The
      ability of pentraxins to interact with numerous ligands (microorganisms, the
      complement system, dead cells, modified plasma proteins, cellular receptors,
      extracellular matrix components, and growth factors) supports their involvement
      in multiple biological functions. As such, the capability of CRP and PTX3 to
      modulate inflammation through the complement system and innate immunity suggests
      their contribution in atherosclerosis, thrombosis, and ischemic heart disease. In
      this review we will overview the key properties of pentraxins and discuss the
      major relevant findings that attribute to pentraxins, particularly CRP and PTX3,
      a biological role in the pathogenesis of cardiovascular disease. 

PMID- 25962567
TI  - [Dyspnoea in Patients with Pulmonary Hypertension (PH) - a Survey in Spezialized
      German PH Centres].
AB  - Dyspnoea is the predominant symptom in patients with pulmonary hypertension (PH)
      at diagnosis. However, since dyspnoea is nonspecific and often occurs in a number
      of common diseases, the presence of PH can easily be underdiagnosed.In addition,
      this symptom underlies a high variability in the subjective perception, therefore
      further diagnostic procedures are often delayed by the patients.A survey of the
      incidence and severity of dyspnoea in 372 patients with PAH was conducted by
      questionnaire in German centres. Age, sex distribution and the range of
      comorbidities corresponded to the findings of national and international
      registries.Approximately 99 % of patients reported the presence of dyspnoea on
      exertion, even at low loads.Remarkably, in 13 % of patients dyspnoea occurs as a
      paroxysmal symptom, which may lead to the differential diagnosis of bronchial
      asthma. In addition, the patients who were being followed in specialized PH
      centres reported an increase in dyspnoea during the last year.The results of the
      survey on the incidence of dyspnoea in patients with PAH are consistent with the
      findings of international studies. 

PMID- 25962568
TI  - [Reduction of Tracheotomy Associated Tracheal Stenosis by Surgical Closure of the
      Tracheostomy].
AB  - BACKGROUND: The most common long-term complication of tracheotomy is the benign
      stenosis of the trachea, which is described for up to 20% of the cases.
      Typically, the stenosis occurs after decannulation in the context of secondary
      wound healing. This study examined whether the closure of the tracheostomy by
      surgical procedure reduces stenosis. METHOD: With the help of our clinical
      database a retrospective analysis of 401 surgical tracheotomies was performed.
      Variables that were recorded were the indication for tracheotomy, the clinical
      course and complications occurred. RESULTS: 155 patients were successfully
      decannulated. In 92 of these patients the tracheostomy was closed by a surgical
      procedure, in 63 cases the closure occurred spontaneously by wound healing. After
      decannulation 3% (n=3) of the surgically closed and 22% (n=14) of the
      spontaneously closed tracheostomies developed a symptomatic tracheal stenosis
      (p<0.001). CONCLUSION: Secondary wound healing of the tracheostomy often leads to
      symptomatic tracheal stenosis. The incidence of symptomatic tracheal stenosis was
      significantly reduced applying closure of the tracheostomy by surgical procedure.

PMID- 25962569
TI  - [Desing and validation of a scale to measure caregiving dedication in caregivers
      of dependent older people].
AB  - OBJECTIVE: To develop and validate a scale to measure caregiving dedication
      regarding activities of daily living in caregivers of dependent older people.
      DESIGN: Cross-sectional study. LOCATION: Primary Health Care (Andalusia, Spain).
      PARTICIPANTS: a probabilistic sample of 200 caregivers of older relatives from
      Cordoba, Spain. MAIN MEASUREMENTS: Content validation by experts, construct
      validity (by exploratory factor analysis), divergent validity and reliability
      (internal consistency, test-retest reliability and inter-observers reliability).
      RESULTS: Cronbach's alpha was 0.86. Intraclass Correlation Coefficient was 0.96
      for test-retest reliability and 0.88 for inter-observers reliability. When the
      sample was divided in two groups according to perceived burden level (presence
      and absence), the perceived burden was significantly different in each group
      (P=.001). The factor analysis revealed one only factor that explained 64% of the
      variance. CONCLUSIONS: The scale allows a suitable measure of caregiving
      dedication regarding activities of daily living in caregivers of older people,
      because this scale allows a quickly, easy administration, is well accepted by
      caregivers, has acceptable psychometric results and includes the frequency of
      caregiving, the kind of attended need and the dependence level in each need.

PMID- 25962570
TI  - [Aims of the publication of care results on health centres].

PMID- 25962571
TI  - [Author's reply].

PMID- 25962572
TI  - [Author's reply].

PMID- 25962573
TI  - [Balneotherapy in osteoarthritis].

PMID- 25962574
TI  - [COOP/WONCA: Reliability and validity of the test administered by telephone].
AB  - AIM: The COOP/WONCA test was initially proposed as a self-report in which the
      answers were supported by drawings illustrating the state investigated.
      Subsequent studies have confirmed its usefulness as a mere verbal self-report
      face-to-face administered. No data have been found about its useful when
      administered by telephone interview. The aim of this study was to determine the
      psychometric properties of the COOP / WONCA test to measure Related Quality of
      Life (HRQoL) administered by telephone and compare them with those obtained in
      other forms of prior administration. DESIGN: Cross-sectional study on a random.
      SETTING: City of Madrid. PARTICIPANTS: Random sample of 802 adult subjects,
      representative of the adult population in Madrid, obtained by stratification from
      the population census. MAIN MEASUREMENTS: Questionnaire COOP/WONCA with 9 items
      included in a broader battery, administered by telephone interview. RESULTS: The
      unrestricted factor analysis points to the unifactoriality of the scale, which
      measures a single latent construct (HRQOL), showing high internal consistency,
      not significantly different from those found by face-to-face administration,
      ruling out the existence of biases in the phone modality. CONCLUSIONS: The
      COOP/WONCA test appears as a reliable and valid measure of HRQOL and telephonic
      administration allows to assume no changes in the results, which can reduce costs
      in population studies, increasing efficiency without loss of quality in the
      information collected.

PMID- 25962575
TI  - Differential influence of propofol and isoflurane anesthesia in a non-human
      primate on the brain kinetics and binding of [(18)F]DPA-714, a positron emission
      tomography imaging marker of glial activation.
AB  - Translocator protein 18 kDa (TSPO) expression at the mitochondrial membrane of
      glial cells is related to glial activation. TSPO radioligands such as [(18)F]DPA
      714 are useful for the non-invasive study of neuroimmune processes using positron
      emission tomography (PET). Anesthetic agents were shown to impact mitochondrial
      function and may influence [(18)F]DPA-714 binding parameters and PET kinetics.
      [(18) F]DPA-714 PET imaging was performed in Papio anubis baboons anesthetized
      using either intravenous propofol (n = 3) or inhaled isoflurane (n = 3). Brain
      kinetics and metabolite-corrected input function were measured to estimate [(18)
      F]DPA-714 brain distribution (VT). Displacement experiments were performed using
      PK11195 (1.5 mg/kg). In vitro [(18)F]DPA-714 binding experiments were performed
      using baboon brain tissue in the absence and presence of tested anesthetics.
      Brain radioactivity peaked higher in isoflurane-anesthetized animals compared
      with propofol (SUVmax = 2.7 +/- 0.5 vs. 1.3 +/- 0.2, respectively) but was not
      different after 30 min. Brain VT was not different under propofol and isoflurane.
      Displacement resulted in a 35.8 +/- 8.4% decrease of brain radioactivity under
      propofol but not under isoflurane (0.1 +/- 7.0%). In vitro, the presence of
      propofol increased TSPO density and dramatically reduced its affinity for
      [(18)F]DPA-714 compared with control. This in vitro effect was not significant
      with isoflurane. Exposure to propofol and isoflurane differentially influences
      TSPO interaction with its specific radioligand [(18)F]DPA-714 with subsequent
      impact on its tissue kinetics and specific binding estimated in vivo using PET.
      Therefore, the choice of anesthetics and their potential influence on PET data
      should be considered for the design of imaging studies using TSPO radioligands,
      especially in a translational research context.

PMID- 25962576
TI  - A Phase I/II adaptive design for heterogeneous groups with application to a
      stereotactic body radiation therapy trial.
AB  - Dose-finding studies that aim to evaluate the safety of single agents are
      becoming less common, and advances in clinical research have complicated the
      paradigm of dose finding in oncology. A class of more complex problems, such as
      targeted agents, combination therapies and stratification of patients by clinical
      or genetic characteristics, has created the need to adapt early-phase trial
      design to the specific type of drug being investigated and the corresponding
      endpoints. In this article, we describe the implementation of an adaptive design
      based on a continual reassessment method for heterogeneous groups, modified to
      coincide with the objectives of a Phase I/II trial of stereotactic body radiation
      therapy in patients with painful osseous metastatic disease. Operating
      characteristics of the Institutional Review Board approved design are
      demonstrated under various possible true scenarios via simulation studies.

PMID- 25962577
TI  - Relative expression of rRNA transcripts and 45S rDNA promoter methylation status
      are dysregulated in tumors in comparison with matched-normal tissues in breast
      cancer.
AB  - Ribosomal RNA (rRNA) expression, one of the most important factors regulating
      ribosome production, is primarily controlled by a CG-rich 45 S rDNA promoter.
      However, the DNA methylation state of the 45 S rDNA promoter, as well as its
      effect on rRNA gene expression in types of human cancers is controversial. In the
      present study we analyzed the methylation status of the rDNA promoter (-380 to
      +53 bp) as well as associated rRNA expression levels in breast cancer cell lines
      and breast tumor-normal tissue pairs. We found that the aforementioned regulatory
      region was extensively methylated (74-96%) in all cell lines and in 68% (13/19
      tumor-normal pairs) of the tumors. Expression levels of rRNA transcripts 18 S, 28
      S, 5.8 S and 45 S external transcribed spacer (45 S ETS) greatly varied in the
      breast cancer cell lines regardless of their methylation status. Analyses of rRNA
      transcript expression levels in the breast tumor and normal matched tissues
      showed no significant difference when normalized with TBP. On the other hand,
      using the geometric mean of the rRNA expression values (GM-rRNA) as reference
      enabled us to identify significant changes in the relative expression of rRNAs in
      the tissue samples. We propose GM-rRNA normalization as a novel strategy to
      analyze expression differences between rRNA transcripts. Accordingly, the 18S
      rRNA/GM-rRNA ratio was significantly higher whereas the 5.8S rRNA/GM-rRNA ratio
      was significantly lower in breast tumor samples than this ratio in the matched
      normal samples. Moreover, the 18S rRNA/GM-rRNA ratio was negatively correlated
      with the 45 S rDNA promoter methylation level in the normal breast tissue
      samples, yet not in the breast tumors. Significant correlations observed between
      the expression levels of rRNA transcripts in the normal samples were lost in the
      tumor samples. We showed that the expression of rRNA transcripts may not be based
      solely on promoter methylation. Carcinogenesis may cause dysregulation of the
      correlation between spliced rRNA expression levels, possibly due to changes in
      rRNA processing, which requires further investigation.

PMID- 25962578
TI  - Snail mediates medial-lateral patterning of the ascidian neural plate.
AB  - The ascidian neural plate exhibits a regular, grid-like arrangement of cells.
      Patterning of the neural plate across the medial-lateral axis is initiated by
      bilateral sources of Nodal signalling, such that Nodal signalling induces
      expression of lateral neural plate genes and represses expression of medial
      neural plate genes. One of the earliest lateral neural plate genes induced by
      Nodal signals encodes the transcription factor Snail. Here, we show that Snail is
      a critical downstream factor mediating this Nodal-dependent patterning. Using
      gain and loss of function approaches, we show that Snail is required to repress
      medial neural plate gene expression at neural plate stages and to maintain the
      lateral neural tube genetic programme at later stages. A comparison of these
      results to those obtained following Nodal gain and loss of function indicates
      that Snail mediates a subset of Nodal functions. Consistently, overexpression of
      Snail can partially rescue a Nodal inhibition phenotype. We conclude that Snail
      is an early component of the gene regulatory network, initiated by Nodal signals,
      that patterns the ascidian neural plate. 

PMID- 25962579
TI  - Agreement Between Experts Regarding Assessment of Postoperative Urinary
      Elimination Nursing Outcomes in Elderly Patients.
AB  - PURPOSE: This study aims to verify the interrater reliability for indicators of
      the Nursing Outcomes Classification of urinary elimination. METHODS: A total of
      103 elderly postoperative patients were followed by two nurses with specialized
      training in medical-surgical and gerontological nursing. FINDINGS: The agreement
      of evaluators was based on interpretation of the Krippendorff's alpha
      coefficient, for complete emptying of the bladder (.928) and presence of
      leukocytes (.885). The amount of urine (.262), density (.425), and urinary
      frequency (.307) had the lowest rates of agreement. IMPLICATIONS FOR NURSING
      PRACTICE: Analysis of urinary elimination could help in clinical follow-up of
      elderly postoperative patients and selection of nursing interventions.

PMID- 25962580
TI  - Neutrophil function in healthy aged horses and horses with pituitary dysfunction.
AB  - Immunosuppression leading to opportunist bacterial infection is a well-recognized
      sequela of equine pituitary pars intermedia dysfunction (PPID). The mechanisms
      responsible for immune dysfunction in PPID however, are as of yet poorly
      characterized. Horses with PPID have high concentrations of hormones known to
      impact immune function including alpha-melanocyte stimulating hormone (alpha-MSH)
      and insulin. alpha-MSH and related melanocortins have been shown in rodents and
      people to impair neutrophil function by decreasing superoxide production (known
      as oxidative burst activity), migration and adhesion. The goal of this study was
      to determine if neutrophil function is impaired in horses with PPID and, if so,
      to determine if plasma alpha-MSH or insulin concentration correlated with the
      severity of neutrophil dysfunction. Specifically, neutrophil phagocytosis,
      oxidative burst activity, chemotaxis and adhesion were assessed. Results of this
      study indicate that horses with PPID have reduced neutrophil function,
      characterized by decreased oxidative burst activity and adhesion. In addition,
      chemotaxis was greater in healthy aged horses than in young horses or aged horses
      with PPID. Plasma insulin: alpha-MSH ratio, but not individual hormone
      concentration was correlated to neutrophil oxidative burst activity. In summary,
      neutrophil function is impaired in horses with PPID, likely due to altered
      hormone concentrations and may contribute to increased risk of opportunistic
      infections. Whether regulation of hormone concentration profiles in horses with
      PPID using therapeutic intervention improves neutrophil function and reduces
      infections needs to be explored. 

PMID- 25962581
TI  - A versatile approach for the site-specific modification of recombinant antibodies
      using a combination of enzyme-mediated bioconjugation and click chemistry.
AB  - A unique two-step modular system for site-specific antibody modification and
      conjugation is reported. The first step of this approach uses enzymatic
      bioconjugation with the transpeptidase Sortase A for incorporation of strained
      cyclooctyne functional groups. The second step of this modular approach involves
      the azide-alkyne cycloaddition click reaction. The versatility of the two-step
      approach has been exemplified by the selective incorporation of fluorescent dyes
      and a positron-emitting copper-64 radiotracer for fluorescence and positron
      emission tomography imaging of activated platelets, platelet aggregates, and
      thrombi, respectively. This flexible and versatile approach could be readily
      adapted to incorporate a large array of tailor-made functional groups using
      reliable click chemistry whilst preserving the activity of the antibody or other
      sensitive biological macromolecules. 

PMID- 25962582
TI  - Nonsuicidal self-injury, suicidal thoughts and suicide attempts among sexual
      minority youth in Ireland during their emerging adult years.
AB  - AIM: This study aimed to examine whether or not sexual minority youth constitute
      an at-risk group for nonsuicidal self-injury, suicidal ideation or suicide
      attempts during their emerging adult years. METHODS: Using data from the
      Challenging Times Study, a population-based study of psychopathology and suicide
      in Ireland, analyses were conducted to test the associations between sexual
      minority status and the odds of any lifetime experience of nonsuicidal self
      injury, suicidal thoughts or suicide attempts among Irish youth aged 19-24 years.
      RESULTS: Sexual minority youth had 6.6-fold (95% CI 1.7-24.7) increased risk of
      nonsuicidal self-injury, a 5.0-fold (95% CI 1.3-18.3) increased risk of suicidal
      ideation, a 7.7-fold (95% CI 1.8-32.0) increased risk of suicide intent and a 6.8
      fold (95% CI 1.6-27.6) increased risk of a suicide attempt during their lifetime
      compared to their heterosexual peers. CONCLUSIONS: This study shows that emerging
      adulthood is a period of risk for suicide and nonsuicidal self-injurious
      behaviour among sexual minority youth.

PMID- 25962584
TI  - Functional up-converting SrTiO3:Er(3+)/Yb(3+) nanoparticles: structural features,
      particle size, colour tuning and in vitro RBC cytotoxicity.
AB  - SrTiO3 nanoparticles co-doped with a broad concentration range of Er(3+) and
      Yb(3+) ions were fabricated using the citric route as a function of annealing
      temperatures of 500-1000  degrees C. The effect of a broad co-dopant
      concentration range and sintering temperature on structural and up-conversion
      properties was investigated in detail by X-ray diffraction techniques and optical
      spectroscopy. The TEM technique was used to estimate the mean particle size,
      which was around 30 nm for the inorganic product annealed at 600  degrees C. Up
      conversion emission color tuning was achieved by particle size control. Power
      dependence of the green and red emissions was found to be a result of temperature
      determination in the operating range of SrTiO3 nanoparticles and a candidate for
      the fast and local microscopic heating and heat release induced by IR
      irradiation. The color changed from white-red-yellow-green upon an increase of
      sintering temperature, inducing changes in the surface-to-volume ratio and the
      number of optically active ions in particle surface regions. The cytotoxic
      activity of nanoparticles on human red blood cells was investigated, showing no
      harmful effects up to a particle concentration of 0.1 mg ml(-1). The cytotoxic
      response of a colloidal suspension of nanoparticles to RBC cells was connected
      with the strong affinity of SrTiO3 particles to the cell membranes, blocking the
      transport of important biological solutes. 

PMID- 25962585
TI  - Tandem inversion duplication within F8 Intron 1 associated with mild haemophilia
      A.
AB  - In approximately 90% of mild haemophilia A (HA) patients, a missense mutation can
      be identified using complete gene sequencing. In this study, multiplex ligation
      dependent probe amplification analysis was performed as a second step in 10
      French-speaking Belgian with mild HA presenting no detectable causal mutation by
      complete sequencing of the factor VIII (FVIII) (F8) gene's 26 exons and its 1.2
      kb of contiguous promoter sequence. This gene dosage technique enabled the
      detection of exon 1 duplications of F8 in three apparently unrelated subjects.
      Using array-comparative genomic hybridization, breakpoint analysis delimited the
      duplication extent to 210 kb in the F8 intron 1 and VBP1 gene intragenic
      position. We postulated that the rearrangement responsible for this duplication,
      never before reported, could be attributed to a symmetrical tandem inversion
      duplication, resulting in a large 233 kb rearrangement of F8 intron 1. This
      rearranged intron should lead to the production of a small number of normal mRNA
      transcripts in relation to the mild HA phenotype. Our analysis of the entire F8
      mRNA from index case 1, particularly the segment containing exons 1-9, revealed
      normal amplification and sequencing. Reduced plasma FVIII antigen levels caused
      by cross-reacting material is associated with a quantitative deficiency of plasma
      FVIII. Male patients were unresponsive to desmopressin (1-deamino-8-D-arginine
      vasopressin). All patients displayed identical F8 haplotypes, despite not being
      related, which suggests a possible founder effect caused by a 210 kb duplication
      involving F8 exon 1. 

PMID- 25962586
TI  - Achievement of Diffusional Independence at Nanoscale Liquid-Liquid Interfaces
      within Arrays.
AB  - In this work, independent radial diffusion at arrayed nanointerfaces between two
      immiscible electrolyte solutions (nanoITIES) was achieved. The arrays were formed
      at nanopores fabricated by focused ion beam milling of silicon nitride (SiN)
      membranes, enabling the reproducible and systematic design of five arrays with
      different ratios of pore center-to-center distance (rc) to pore radius (ra).
      Voltammetry across water-1,6-dichlorohexane nanoITIES formed at these arrays was
      examined by the interfacial transfer of tetrapropylammonium ions. The diffusion
      limited ion-transfer current increased with the ratio rc/ra, reaching a plateau
      for rc/ra >= 56, which was equivalent to the theoretical current for radial
      diffusion to an array of independent nanoITIES. As a result, mass transport to
      the nanoITIES arrays was greatly enhanced due to the decreased overlap of
      diffusion zones at adjacent nanoITIES, allowing each interface in the array to
      behave independently. When the rc/ra ratio increased from 13 to 56, the
      analytical performance parameters of sensitivity and limit of detection were
      improved from 0.50 (+/-0.02) A M(-1) to 0.76 (+/-0.02) A M(-1) and from 0.101 (+/
      0.003) MUM to 0.072 (+/-0.002) MUM, respectively. These results provide an
      experimental basis for the design of arrayed nanointerfaces for electrochemical
      sensing. 

PMID- 25962587
TI  - Emerging aspects of treatment in mitochondrial disorders.
AB  - Mitochondrial diseases are clinically, biochemically and genetically
      heterogeneous disorders of two genomes, for which effective curative therapies
      are currently lacking. With the exception of a few rare vitamin/cofactor
      responsive conditions (including ACAD9 deficiency, disorders of coenzyme Q(10)
      biosynthesis, and Leigh syndrome caused by mutations in the SLC19A3 transporter),
      the mainstay of treatment for the vast majority of patients involves supportive
      measures. The search for a cure for mitochondrial disease is the subject of
      intensive research efforts by many investigators across the globe, but the goal
      remains elusive. The clinical and genetic heterogeneity, multisystemic nature of
      many of these disorders, unpredictable natural course, relative inaccessibility
      of the mitochondrion and lack of validated, clinically meaningful outcome
      measures, have all presented great challenges to the design of rigorous clinical
      trials. This review discusses barriers to developing effective therapies for
      mitochondrial disease, models for evaluating the efficacy of novel treatments and
      summarises the most promising emerging therapies in six key areas: 1) antioxidant
      approaches; 2) stimulating mitochondrial biogenesis; 3) targeting mitochondrial
      membrane lipids, dynamics and mitophagy; 4) replacement therapy; 5) cell-based
      therapies; and 6) gene therapy approaches for both mtDNA and nuclear-encoded
      defects of mitochondrial metabolism.

PMID- 25962588
TI  - Differences in brain gene transcription profiles advocate for an important role
      of cognitive function in upstream migration and water obstacles crossing in
      European eel.
AB  - BACKGROUND: European eel is a panmictic species, whose decline has been recorded
      since the last 20 years. Among human-induced environmental factors of decline,
      the impact of water dams during species migration is questioned. The main issue
      of this study was to pinpoint phenotypic traits that predisposed glass eels to
      successful passage by water barriers. The approach of the study was individual
      centred and without any a priori hypothesis on traits involved in the putative
      obstacles selective pressure. We analyzed the transcription level of 14,913
      genes. RESULTS: Transcriptome analysis of three tissues (brain, liver and muscle)
      from individuals sampled on three successive forebays separated by water
      obstacles indicated different gene transcription profiles in brain between the
      two upstream forebays. No differences in gene transcription levels were observed
      in liver and muscle samples among segments. A total of 26 genes were
      differentially transcribed in brain. These genes encode for, among others,
      keratins, cytokeratins, calcium binding proteins (S100 family), cofilin,
      calmodulin, claudin and thy-1 membrane glycoprotein. The functional analysis of
      these genes highlighted a putative role of cytoskeletal dynamics and synaptic
      plasticity in fish upstream migration. CONCLUSION: Synaptic connections in brain
      are solicited while eels are climbing the obstacles with poorly designed
      fishways. Successful passage by such barriers can be related to spatial learning
      and spatial orientation abilities when fish is out of the water.

PMID- 25962589
TI  - Quantifying [18F]fluorodeoxyglucose uptake in the arterial wall: the effects of
      dual time-point imaging and partial volume effect correction.
AB  - PURPOSE: The human arterial wall is smaller than the spatial resolution of
      current positron emission tomographs. Therefore, partial volume effects should be
      considered when quantifying arterial wall (18)F-FDG uptake. We evaluated the
      impact of a novel method for partial volume effect (PVE) correction with contrast
      enhanced CT (CECT) assistance on quantification of arterial wall (18)F-FDG uptake
      at different imaging time-points. METHODS: Ten subjects were assessed by CECT
      imaging and dual time-point PET/CT imaging at approximately 60 and 180 min after
      (18)F-FDG administration. For both time-points, uptake of (18)F-FDG was
      determined in the aortic wall by calculating the blood pool-corrected maximum
      standardized uptake value (cSUVMAX) and cSUVMEAN. The PVE-corrected SUVMEAN
      (pvcSUVMEAN) was also calculated using (18)F-FDG PET/CT and CECT images. Finally,
      corresponding target-to-background ratios (TBR) were calculated. RESULTS: At 60
      min, pvcSUVMEAN was on average 3.1 times greater than cSUVMAX (P < .0001) and 8.5
      times greater than cSUVMEAN (P < .0001). At 180 min, pvcSUVMEAN was on average
      2.6 times greater than cSUVMAX (P < .0001) and 6.6 times greater than cSUVMEAN (P
      < .0001). CONCLUSION: This study demonstrated that CECT-assisted PVE correction
      significantly influences quantification of arterial wall (18)F-FDG uptake.
      Therefore, partial volume effects should be considered when quantifying arterial
      wall (18)F-FDG uptake with PET.

PMID- 25962590
TI  - Diagnostic accuracy of 11C-choline PET/CT in comparison with CT and/or MRI in
      patients with hepatocellular carcinoma.
AB  - PURPOSE: In recent decades, the use of radiopharmaceuticals in the assessment of
      hepatocellular carcinoma (HCC) has become established, and new findings indicate
      that radiolabelled choline has considerable potential in this setting. Therefore,
      in this study we aimed to assess the diagnostic role of (11)C-choline positron
      emission tomography (PET)/CT, compared with conventional imaging with CT/MRI, in
      patients with HCC. METHODS: The study population comprised 45 patients (male to
      female ratio = 37:8, median age 70.5 years) referred to our institution owing to
      HCC: 27 at initial diagnosis and 18 for restaging after recurrence. In all cases
      we performed whole-body (11)C-choline PET/CT and compared its findings with
      contrast-enhanced CT (n = 35) or MRI (n = 29) or both (n = 15) for a total of 50
      paired scans. The reference standard was either histological proof (21 patients)
      or a multidisciplinary consensus. Diagnostic accuracy was then determined in a
      scan-based (SBA) and a lesion-based analysis (LBA). RESULTS: On SBA the
      sensitivity and specificity for PET were 88 and 90 %, respectively, whereas for
      CT/MRI they were 90 and 73 %, respectively (p > 0.05). On LBA the overall
      sensitivity and specificity were 78 and 86 %, respectively, for PET vs 65 and 55
      % for CT/MRI. Overall we investigated 168 disease sites, of which 100 were in the
      liver and 68 were extrahepatic. When considering only liver lesions, (11)C
      choline PET and CT/MRI showed an accuracy of 66 and 85 %, respectively, while for
      extrahepatic lesions PET showed an accuracy of 99 %, while the accuracy of CT/MRI
      was 32 %. In both cases, there was a statistically significant difference in
      accuracy between the two modalities (p < 0.01). Combination of the PET results
      with those of CT/MRI resulted in the highest diagnostic accuracy in both
      analyses, at 92 % for SBA and 96 % for LBA. In 11 patients (24 %) the PET
      findings modified the therapeutic strategy, the modification proving appropriate
      in 10 of them. CONCLUSION: (11)C-Choline PET showed good accuracy in
      investigating patients with HCC and prompted a change in treatment planning in
      almost one fourth of patients. The main strength of (11)C-choline PET/CT resides
      in its ability to detect extrahepatic HCC localizations, but the combination with
      conventional imaging modalities allowed for the highest diagnostic accuracy.

PMID- 25962591
TI  - Erratum to: Modeling precision treatment of breast cancer.
AB  - During the type-setting of the final version of the article [1] some of the
      additional files were swapped. The correct files are republished in this Erratum.

PMID- 25962592
TI  - Further characterization of "subject's own name (SON) negativity," an ERP
      component reflecting early preattentive detection of SON.
AB  - BACKGROUND: Subject's own name (SON) is detected automatically and unconsciously
      in the brain. SON negativity, an early wave in the mismatch negativity latency
      range, has been proposed as a potential event-related potential (ERP) index of
      the automatic preattentive detection of SON. SON negativity is probably not a
      general measure of familiarity, as it is not elicited by the subject's parent's
      name. We further investigated the specificity of this response by testing whether
      it is elicited by a name to which subjects were strongly but only temporarily
      familiarized. FINDINGS: Subjects performed a task to detect an arbitrary
      unfamiliar name for forty minutes. Then, that name was presented randomly and
      equiprobably with nine novel unfamiliar names while they played a video game and
      tried to ignore the sounds. SON negativity was not elicited, even when subjects
      spontaneously noticed hearing the familiarized name. CONCLUSIONS: The finding
      supports the notion that SON negativity represents a specific ERP measure of the
      early preattentive detection of SON, rather than a general measure of
      familiarity.

PMID- 25962593
TI  - ATP-binding cassette subfamily B member 1 (ABCB1) and subfamily C member 10
      (ABCC10) are not primary resistance factors for cabazitaxel.
AB  - INTRODUCTION: ATP-binding cassette subfamily B member 1 (ABCB1) and subfamily C
      member 10 (ABCC10) proteins are efflux transporters that couple the energy
      derived from ATP hydrolysis to the translocation of toxic substances and
      chemotherapeutic drugs out of cells. Cabazitaxel is a novel taxane that differs
      from paclitaxel by its lower affinity for ATP-binding cassette (ABC)
      transporters. METHODS: We determined the effects of cabazitaxel, a novel tubulin
      binding taxane, and paclitaxel on paclitaxel-resistant, ABCB1-overexpressing KB
      C2 and LLC-MDR1-WT cells and paclitaxel-resistant, ABCC10-overexpressing
      HEK293/ABCC10 cells by calculating the degree of drug resistance and measuring
      ATPase activity of the ABCB1 transporter. RESULTS: Decreased resistance to
      cabazitaxel compared with paclitaxel was observed in KB-C2, LLC-MDR1-WT, and
      HEK293/ABCC10 cells. Moreover, cabazitaxel had low efficacy, whereas paclitaxel
      had high efficacy in stimulating the ATPase activity of ABCB1, indicating a
      direct interaction of both drugs with the transporter. CONCLUSION: ABCB1 and
      ABCC10 are not primary resistance factors for cabazitaxel compared with
      paclitaxel, suggesting that cabazitaxel may have a low affinity for these efflux
      transporters.

PMID- 25962594
TI  - Influence of hospitalization on prescribing safety across the continuum of care:
      an exploratory study.
AB  - BACKGROUND: Transitions between different levels of healthcare, such as hospital
      admission and discharge, pose a considerable threat to the quality and continuity
      of drug therapy. This study aims to further explore the current role of
      hospitalization in prescribing error exposure and medication-related
      communication as patients are transferred from and back to ambulatory care.
      METHODS: Assisted by electronic decision support, pre-admission and discharge
      medication regimens of 187 adult patients in a German university hospital were
      comparatively screened for clinically relevant categories of potentially
      inadequate prescribing. Binary logistic regression analyses were conducted to
      identify risk factors predisposing individuals to prescribing errors as a result
      of hospitalization. Additionally, it was established to what extent medication
      changes and potentially inappropriate prescribing decisions originating from
      inpatient treatment were communicated in discharge letters. RESULTS: 94.7% of the
      patients are subjected to differences between pre-admission and discharge
      prescriptions occurring at a rate of 461 per 100 hospitalizations. However, these
      modifications in drug therapy do not have a significant effect on the total
      number of potential prescribing errors per patient (p = 0.135) even though a
      large potential for improvement exists throughout the care continuum. For
      instance, almost a quarter of study participants with impaired kidney function
      lacks appropriate dose adjustment for one or more drugs before onset and at the
      end of inpatient treatment alike (22.5% [95% CI: 13.5%-34.0%] vs. 22.8% [95% CI:
      14.1%-33.6%]). Overall, the probability of error exposure following
      hospitalization rises with an increasing number of prescribed drugs per patient,
      while individuals treated on surgical wards are four times more likely to be
      discharged with a prescribing-related safety hazard than their counterparts from
      medical departments (OR: 4.069 [95% CI: 1.126-14.703]; p = 0.032). In the study
      population's discharge summaries only 14.8% of medication changes and none of the
      potentially inappropriate prescribing decisions made during inpatient care are
      addressed, despite the latter occurring at a rate of 91 per 100 hospitalizations.
      CONCLUSIONS: There is urgent need for standardized and evidence-based measures
      contributing to patient safety across sectorial interfaces of drug therapy. Our
      findings provide useful orientation for the targeted and rational design of such
      improvement strategies.

PMID- 25962595
TI  - Vagally mediated heart rate variability in headache patients--a systematic review
      and meta-analysis.
AB  - OBJECTIVE: Vagal nerve activity-indexed by heart rate variability (HRV)-has been
      linked to altered pain processing and inflammation, both of which may underpin
      headache disorders and lead to cardiovascular disease (CVD). Here we examined the
      evidence for differences in parasympathetic (vagal) activity indexed by time- and
      frequency-domain measures of HRV in patients with headache disorders compared to
      healthy controls (HCs). METHODS: A systematic review and meta-analysis was
      conducted on studies investigating group differences in vagally mediated HRV
      (vmHRV) including time- (root-mean-square of successive R-R-interval differences
      (RMSSD)) and frequency- (high-frequency HRV) domain measures. Studies eligible
      for inclusion were identified by a systematic search of the literature, based on
      the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
      statement. RESULTS: Seven studies reporting a total of 10 comparisons of patients
      with headache disorders (HF-HRV n = 67, RMSSD n = 122) and HCs (HF-HRV n = 64,
      RMSSD n = 125) were eligible for inclusion. Random-effects meta-analysis revealed
      a significant main effect on RMSSD (Z = 2.03, p = 0.04; Hedges' g = -0.63; 95% CI
      (-1.24, -0.02); k = 6) and similar pooled effect size estimates for HF-HRV when
      breathing was controlled (g = -0.30; 95% CI (-0.69; 0.10)) but not when breathing
      was not controlled (g = 0.02; 95% CI (-0.69; 0.74)). Controlling for breathing
      had no effect on RMSSD. CONCLUSION: vmHRV is reduced in patients with headache
      disorders, findings associated with a medium effect size. Suggestions for future
      research in this area are provided, emphasizing a need to investigate the impact
      of headache disorders and commonly comorbid conditions-including mental disorders
      as well as the investigation of the risk for CVD in migraine in particular. We
      further emphasize the need for large-scale studies to investigate HRV as a
      mechanism mediating the association of migraine and CVD.

PMID- 25962596
TI  - Video studies of passage by Anopheles gambiae mosquitoes through holes in a
      simulated bed net: effects of hole size, hole orientation and net environment.
AB  - BACKGROUND: Holes in netting provide potential routes for mosquitoes to enter
      ITNs. Despite this, there is little information on how mosquitoes respond to
      holes in bed nets and how their responses are affected by hole size, shape and
      orientation or by ambient conditions around the net. METHODS: Female Anopheles
      gambiae (G3) were recorded in a simulated bed net consisting of two sizes of
      untreated netting-covered behavioural arenas placed above and beside (to simulate
      the bed net roof and sides respectively) the experimenter who was a source of
      host cues from 'inside' the net. A round hole of 9 mm or 13 mm diameter was cut
      into the centre of the netting of each arena. Videos of unfed female mosquitoes
      in arenas were analysed for time spent flying, walking and standing still and for
      exit through the hole. The effects of the experimenter on temperature and
      relative humidity around the simulated net were also measured. RESULTS:
      Mosquitoes were significantly more active in overhead arenas than in arenas to
      the side. Hole passage was significantly more likely in smaller arenas than
      larger ones and for larger holes than smaller ones. In arenas to the side, hole
      passage rate through small holes was about 50% less likely than what could be
      explained by area alone. Passage rate through holes in overhead arenas was
      consistent with hole area. Temperature in arenas did not strongly reflect the
      experimenter's presence in the simulated net. Relative humidity and absolute
      humidity in overhead arenas, but not in arenas to the side, were immediately
      affected by experimenter presence. CONCLUSIONS: Higher levels of activity in
      overhead arenas than in arenas to the side were likely due to the rising heat and
      humidity plume from the experimenter. Lower than expected passage rates through
      smaller vertically oriented holes may have been be due to an edge effect that
      does not apply to horizontally oriented holes. Results suggest that current
      methods of assessing the importance of physical damage to ITNs may not accurately
      reflect mosquito entry risk in all cases.

PMID- 25962597
TI  - CT brush and CancerZap!: two video games for computed tomography dose
      minimization.
AB  - BACKGROUND: X-ray dose from computed tomography (CT) scanners has become a
      significant public health concern. All CT scanners spray x-ray photons across a
      patient, including those using compressive sensing algorithms. New technologies
      make it possible to aim x-ray beams where they are most needed to form a
      diagnostic or screening image. We have designed a computer game, CT Brush, that
      takes advantage of this new flexibility. It uses a standard MART algorithm
      (Multiplicative Algebraic Reconstruction Technique), but with a user defined
      dynamically selected subset of the rays. The image appears as the player moves
      the CT brush over an initially blank scene, with dose accumulating with every
      "mouse down" move. The goal is to find the "tumor" with as few moves (least dose)
      as possible. RESULTS: We have successfully implemented CT Brush in Java and made
      it available publicly, requesting crowdsourced feedback on improving the open
      source code. With this experience, we also outline a "shoot 'em up game"
      CancerZap! for photon limited CT. CONCLUSIONS: We anticipate that human computing
      games like these, analyzed by methods similar to those used to understand eye
      tracking, will lead to new object dependent CT algorithms that will require
      significantly less dose than object independent nonlinear and compressive sensing
      algorithms that depend on sprayed photons. Preliminary results suggest
      substantial dose reduction is achievable.

PMID- 25962599
TI  - Economic crisis and mortality by suicide: two concepts hard to link.

PMID- 25962600
TI  - Maximising the fourth year of medical school.

PMID- 25962598
TI  - Implementation and evaluation of the VA DPP clinical demonstration: protocol for
      a multi-site non-randomized hybrid effectiveness-implementation type III trial.
AB  - BACKGROUND: The Diabetes Prevention Program (DPP) study showed that lifestyle
      intervention resulted in a 58% reduction in incidence of type 2 diabetes among
      individuals with prediabetes. Additional large randomized controlled trials have
      confirmed these results, and long-term follow-up has shown sustained benefit 10
      20 years after the interventions ended. Diabetes is a common and costly disease,
      especially among Veterans, and despite strong evidence supporting the feasibility
      of type 2 diabetes prevention, the DPP has not been widely implemented. The first
      aim of this study will evaluate implementation of the Veterans Affairs (VA) DPP
      in three VA medical centers. The second aim will assess weight and hemoglobin A1c
      (A1c) outcomes, and the third aim will determine the cost-effectiveness and
      budget impact of implementation of the VA DPP from a health system perspective.
      METHODS/DESIGN: This partnered multi-site non-randomized systematic assignment
      study will use a highly pragmatic hybrid effectiveness-implementation type III
      mixed methods study design. The implementation and administration of the VA DPP
      will be funded by clinical operations while the evaluation of the VA DPP will be
      funded by research grants. Seven hundred twenty eligible Veterans will be
      systematically assigned to the VA DPP clinical demonstration or the usual care VA
      MOVE!(r) weight management program. A multi-phase formative evaluation of the VA
      DPP implementation will be conducted. A theoretical program change model will be
      used to guide the implementation process and assess applicability and feasibility
      of the DPP for VA. The Consolidated Framework for Implementation Research (CFIR)
      will be used to guide qualitative data collection, analysis, and interpretation
      of barriers and facilitators to implementation. The RE-AIM framework will be used
      to assess Reach, Effectiveness, Adoption, Implementation, and Maintenance of the
      VA DPP. Twelve-month weight and A1c change will be evaluated for the VA DPP
      compared to the VA MOVE! PROGRAM: Mediation analyses will be conducted to
      identify whether program design differences impact outcomes. DISCUSSION: Findings
      from this pragmatic evaluation will be highly applicable to practitioners who are
      tasked with implementing the DPP in clinical settings. In addition, findings will
      determine the effectiveness and cost-effectiveness of the VA DPP in the Veteran
      population.

PMID- 25962601
TI  - Macrophage activity assessed by soluble CD163 in early rheumatoid arthritis:
      association with disease activity but different response patterns to synthetic
      and biologic DMARDs.
AB  - OBJECTIVES: Rheumatoid arthritis (RA) is a chronic autoimmune disease where TNF
      alpha is a central mediator of inflammation, and is cleaved from the cell surface
      by TACE/ADAM17. This metalloproteinase is also responsible for the release of
      soluble (s) CD163. Soluble CD163 reflects macrophage activation. In RA, sCD163
      has been suggested as a marker of disease activity and progression. Our aim is to
      investigate sCD163 levels in early RA patients. METHODS: Soluble CD163 was
      measured by ELISA from 150 RA plasma samples from the OPERA trial. Averaged
      disease duration was three months, prior to randomisation with methotrexate (MTX)
      and adalimumab (DMARD+ADA) or MTX and placebo (DMARD+PLA). Soluble CD163 levels
      were evaluated in relation to clinical disease parameters. RESULTS: Plasma sCD163
      at baseline was 2.39 mg/l (1.74 mg/l-3.18 mg/l), mean (95% CI), vs healthy
      controls: 1.63 mg/l (1.54 mg/l - 1.73 mg/l), (p<0.001). After three months of
      treatment sCD163 levels decreased significantly (average 23.5%) in both treatment
      groups. Significant incremental sCD163 levels followed withdrawal of ADA after 12
      months of treatment. Baseline sCD163 correlated with CRP and all investigated
      disease activity markers (rho=0.16-0.28, p<0.05). In the DMARD+PLA group baseline
      sCD163 also correlated with CRP during the follow-up period. CONCLUSIONS: Soluble
      CD163 correlated with disease activity markers in early RA before treatment.
      Plasma sCD163 may add to currently available disease measures by specifically
      reflecting changes in macrophage activity as evidenced by increasing levels
      following anti-TNF withdrawal, despite maintenance of a stable clinical condition
      achieved by conventional remedies. It remains to be determined whether sCD163 is
      an early predictor of disease flare.

PMID- 25962602
TI  - Working memory's workload capacity.
AB  - We examined the role of dual-task interference in working memory using a novel
      dual two-back task that requires a redundant-target response (i.e., a response
      that neither the auditory nor the visual stimulus occurred two back versus a
      response that one or both occurred two back) on every trial. Comparisons with
      performance on single two-back trials (i.e., with only auditory or only visual
      stimuli) showed that dual-task demands reduced both speed and accuracy. Our task
      design enabled a novel application of Townsend and Nozawa's (Journal of
      Mathematical Psychology 39: 321-359, 1995) workload capacity measure, which
      revealed that the decrement in dual two-back performance was mediated by the
      sharing of a limited amount of processing capacity. Relative to most other single
      and dual n-back tasks, performance measures for our task were more reliable, due
      to the use of a small stimulus set that induced a high and constant level of
      proactive interference. For a version of our dual two-back task that minimized
      response bias, accuracy was also more strongly correlated with complex span than
      has been found for most other single and dual n-back tasks. 

PMID- 25962603
TI  - Tipping points and early warning signals in the genomic composition of
      populations induced by environmental changes.
AB  - We live in an ever changing biosphere that faces continuous and often stressing
      environmental challenges. From this perspective, much effort is currently devoted
      to understanding how natural populations succeed or fail in adapting to evolving
      conditions. In a different context, many complex dynamical systems experience
      critical transitions where their dynamical behaviour or internal structure
      changes suddenly. Here we connect both approaches and show that in rough and
      correlated fitness landscapes, population dynamics shows flickering under small
      stochastic environmental changes, alerting of the existence of tipping points.
      Our analytical and numerical results demonstrate that transitions at the genomic
      level preceded by early-warning signals are a generic phenomenon in constant and
      slowly driven landscapes affected by even slight stochasticity. As these genomic
      shifts are approached, the time to reach mutation-selection equilibrium
      dramatically increases, leading to the appearance of hysteresis in the
      composition of the population. Eventually, environmental changes significantly
      faster than the typical adaptation time may result in population extinction. Our
      work points out several indicators that are at reach with current technologies to
      anticipate these sudden and largely unavoidable transitions. 

PMID- 25962604
TI  - Expression of bone morphogenetic proteins 4, 6 and 7 is downregulated in kidney
      allografts with interstitial fibrosis and tubular atrophy.
AB  - PURPOSE: Bone morphogenetic proteins (BMPs) are pleiotropic growth factors. This
      paper investigates the connection between the expression pattern of BMPs in
      kidney allograft tissue versus the cause of allograft dysfunction. METHODS: The
      expression pattern of BMP2, BMP4, BMP6 and BMP7 in 50 kidney allografts obtained
      by transplant nephrectomy is investigated. Immunohistochemical staining is
      semiquantitatively evaluated for intensity to identify the expression pattern of
      BMPs in normal and allograft kidney tissues. RESULTS: The expression of BMP4 is
      unique between different tubular cell types in grafts without signs of fibrosis.
      This effect is not found in specimens with high grades of interstitial fibrosis
      and tubular atrophy (IFTA). In samples with IFTA grades II and III, the BMP7
      expression is reduced in a significant fraction of specimens relative to those
      without signs of IFTA. The expression pattern of BMP6 indicates that its
      activation may be triggered by the act of transplantation and subsequent
      reperfusion injury. The expression of BMP2 is strong in all types of tubular
      epithelial cells and does not differ between the compared allografts and control
      kidney specimens. CONCLUSION: The intensity and expression pattern of BMP4, BMP6
      and BMP7 in transplanted kidney tissue are found to be dependent upon the length
      of the transplanted period, the clinical indication for transplant nephrectomy
      and signs of IFTA in kidney tissue.

PMID- 25962606
TI  - Unusual cause of right iliac fossa pain: extra-peritoneal omentum with torsion.

PMID- 25962605
TI  - Sudden cardiac death in CKD patients.
AB  - The risk of sudden cardiac death (SCD) is high in chronic kidney disease
      patients, and it increases with the progression of kidney function deterioration.
      The most common causes of SDC are the following: ventricular tachycardia,
      ventricular tachyarrhythmia, tachycardia torsade de pointes, sustained
      ventricular fibrillation and bradyarrhythmia. Dialysis influences cardiovascular
      system and results in hemodynamic disturbances as well as electrolyte shifts
      altering myocardial electrophysiology. Studies suggest that this procedure exerts
      both detrimental (poor volume control can exacerbate hypertension and left
      ventricle hypertrophy) and beneficial effects (associated with fluid removal and
      subsequent decrease in left ventricle stretch). Dialysis-related vulnerability to
      serious arrhythmias is the result of sudden shifts in fluid status and
      electrolytes, particularly potassium, which alter the physiological milieu. Also
      Ca(2+) ions, in which concentration alters during dialysis, are of key importance
      in the contraction of vascular smooth muscle cells and cardiac myocytes, thus
      exerting significant effects on hemodynamics. Due to the fact that SCD occurs
      with similar frequency in peritoneal dialysis and in hemodialysis patients, it
      seems that end-stage renal disease factors are more important than the specific
      ones associated with dialysis type. The results of randomized trials suggested
      that hemodialysis patients may not derive the same benefit of cardiovascular
      disease therapy including beta-blockers, calcium channel blockers and angiotensin
      converting enzyme inhibitors as the general population with normal kidney
      function. Noninvasive tests used to stratify SCD risk in HD patients have poor
      positive value, and thus, combining tests including HRV, baroreceptor sensitivity
      and effectiveness index as well as its function indices and heart rate turbulence
      should be implemented. There are only few large randomized placebo-controlled
      trials assessing the influence of cardioprotective medications or implantable
      cardioverter defibrillator (ICD) implantation in dialysis patients on life
      quality and survival, and their results are sometimes contradictory. The decision
      concerning treatment and/or ICD implantation in this group of patients should be
      made on the basis of careful assessment of individual risk factors. Moreover, due
      to the high hazard of cardiovascular mortality including SCD in dialysis
      patients, physicians should concentrate on the early selection of high-risk
      patients, monitoring them and introduction of preventive measures. 

PMID- 25962608
TI  - Erratum: Different forms of effective connectivity in primate frontotemporal
      pathways.

PMID- 25962607
TI  - Prevalence of recurrent pathogenic microdeletions and microduplications in over
      9500 pregnancies.
AB  - OBJECTIVES: The implementation of chromosomal microarray analysis (CMA) in
      prenatal testing for all patients has not achieved a consensus. Technical
      alternatives such as Prenatal BACs-on-Beads(TM) (PNBoBs(TM) ) have thus been
      applied. The aim of this study was to provide the frequencies of the
      submicroscopic defects detectable by PNBoBs(TM) under different prenatal
      indications. METHODS: A total of 9648 prenatal samples were prospectively
      analyzed by karyotyping plus PNBoBs(TM) and classified by prenatal indication.
      The frequencies of the genomic defects and their 95%CIs were calculated for each
      indication. RESULTS: The overall incidence of cryptic imbalances was 0.7%. The
      majority involved the DiGeorge syndrome critical region (DGS). The additional
      diagnostic yield of PNBoBs(TM) in the population with a low a priori risk was
      1/298. The prevalences of DGS microdeletion and microduplication in the low-risk
      population were 1/992 and 1/850, respectively. CONCLUSIONS: The constant a priori
      risk for common pathogenic cryptic imbalances detected by this technology is
      estimated to be ~0.3%. A prevalence higher than that previously estimated was
      found for the 22q11.2 microdeletion. Their frequencies were independent of
      maternal age. These data have implications for cell-free DNA screening tests
      design and justify prenatal screening for 22q11 deletion, as early recognition of
      DGS improves its prognosis.

PMID- 25962609
TI  - Validated Method for the Quantification of Buprenorphine in Postmortem Blood
      Using Solid-Phase Extraction and Two-Dimensional Gas Chromatography-Mass
      Spectrometry.
AB  - A highly sensitive and fully validated method was developed for the
      quantification of buprenorphine in postmortem blood. After a two-step protein
      precipitation process using acetonitrile, buprenorphine was purified using mixed
      mode (C8/cation exchange) solid-phase extraction cartridges. Endogenous water
      soluble compounds and lipids were removed from the cartridges before the samples
      were eluted, concentrated and derivatized using N-methyl-N
      trimethylsilyltrifluoroacetamide. The samples were analyzed using two-dimensional
      gas chromatography-mass spectrometry (2D GC-MS) in selective ion-monitoring mode.
      A low polarity Rxi((r))-5MS (30 m * 0.25 mm I.D. * 0.25 um) was used as the
      primary column and the secondary column was a mid-polarity Rxi((r)) -17Sil MS (15
      m * 0.32 mm I.D. * 0.25 um). The assay was linear from 1.0 to 50.0 ng/mL (r(2) >
      0.99; n = 6). Intraday (n = 6) and interday (n = 9) imprecisions (percentage
      relative standard deviation, % RSD) were <5% and the average recovery was 60%.
      The limit of detection (LOD) of the method was 0.5 ng/mL and limit of
      quantification was 1.0 ng/mL. 2D GC-MS improved the LOD of buprenorphine by 20
      fold compared with analysis on a conventional GC-MS. The method was highly
      selective with no interference from endogenous compounds or from 62 commonly
      encountered drugs. To prove method applicability to forensic postmortem cases, 14
      authentic postmortem blood samples were analyzed. 

PMID- 25962610
TI  - Prescription Opioids. IV: Disposition of Hydrocodone in Oral Fluid and Blood
      Following Single-Dose Administration.
AB  - The Substance Abuse and Mental Health Services Administration (SAMHSA) is
      currently evaluating hydrocodone (HC) for inclusion in the Mandatory Guidelines
      for Federal Workplace Drug Testing Programs. This study evaluated the time course
      of HC, norhydrocodone (NHC), dihydrocodeine (DHC) and hydromorphone (HM) in
      paired oral fluid and whole blood specimens by liquid chromatography-tandem mass
      spectrometry (limit of quantitation = 1 ng/mL of oral fluid, 5 ng/mL of blood)
      over a 52-h period. A single dose of HC bitartrate, 20 mg, was administered to 12
      subjects. Analyte prevalence was as follows: oral fluid, HC > NHC > DHC; and
      blood, HC > NHC. HM was not detected in any specimen. HC was frequently detected
      within 15 min in oral fluid and 30 min in blood. Mean oral fluid to blood (OF :
      BL) ratios and correlations were 3.2 for HC (r = 0.73) and 0.7 for NHC (r =
      0.42). The period of detection for oral fluid exceeded blood at all evaluated
      thresholds. At a 1-ng/mL threshold for oral fluid, mean detection time was 30 h
      for HC and 18 h for NHC and DHC. This description of HC and metabolite
      disposition in oral fluid following single-dose administration provides valuable
      interpretive guidance of HC test results. 

PMID- 25962611
TI  - Randomized trial of anaesthetic interventions in external cephalic version for
      breech presentation.
AB  - BACKGROUND: Successful external cephalic version (ECV) for breech presenting
      fetus reduces the need for Caesarean section (CS). We aimed to compare the
      success rate of ECV with either spinal anaesthesia (SA) or i.v. analgesia using
      remifentanil. METHODS: In a double-phased, stratified randomized blinded
      controlled study we compared the success rates of ECV, performed under spinal
      anaesthesia (SA), i.v. analgesia (IVA) using remifentanil or no anaesthetic
      interventions. In phase I, 189 patients were stratified by parity before
      randomization to ECV, performed by blinded operators, under SA using either
      hyperbaric bupivacaine 9 mg with fentanyl 15 ug, i.v. remifentanil infusion 0.1
      ug kg min(-1), or Control (no anaesthetic intervention). Operators performing ECV
      were blinded to the treatment allocation. In phase 2, patients in the Control
      group in whom the initial ECV failed were further randomized to receive either SA
      (n=9) or IVA (n=9) for a re-attempt. The primary outcome was the incidence of
      successful ECV. RESULTS: The success rate in Phase 1 was greatest using SA [52/63
      (83%)], compared with IVA [40/63 (64%)] and Control [40/63 (64%)], (P=0.027).
      Median [IQR] pain scores on a visual analogue scale (range 0-100), were 0 [0-0]
      with SA, 35 [0-60] with IVA and 50 [30-75] in the Control group (P<0.001). Median
      [IQR] VAS sedation scores were highest with IVA [75 (50-80)], followed by SA, [0
      (0-50)] and Control [0 (0-0)]. In phase 2, 7/9 (78%) of ECV re-attempts were
      successful with SA, whereas all re-attempts using IVA failed (P=0.0007). The
      incidence of fetal bradycardia necessitating emergency CS within 30 min, was
      similar among groups; 1.6% (1/63) in the SA and IVA groups and 3.2% (2/63) in the
      Control group. CONCLUSIONS: SA increased the success rate and reduced pain for
      both primary and re-attempts of ECV, whereas IVA using remifentanil infusion only
      reduced the pain. There was no significant increase in the incidence of fetal
      bradycardia or emergency CS, with ECV performed under anaesthetic interventions.
      Relaxation of the abdominal muscles from SA appears to underlie the improved
      outcomes for ECV.

PMID- 25962612
TI  - Predictors for postoperative nausea and vomiting after xenon-based anaesthesia.
AB  - BACKGROUND: In contrast to volatile anaesthetics, xenon acts by antagonism at N
      methyl-d-aspartate receptors and antagonizes 5-hydroxytryptamine type 3 receptors
      that mediate nausea and vomiting. Therefore, it is unknown whether the same risk
      factors for postoperative nausea and vomiting (PONV) after volatile anaesthetics
      apply to xenon-based anaesthesia. METHODS: With ethics committee approval and
      written informed consent, 502 consecutive patients undergoing xenon-based
      anaesthesia were included in a multicentre prospective observational study.
      Antiemetic prophylaxis was administered at the discretion of the attending
      anaesthetists. Postoperative nausea and vomiting and need for antiemetic rescue
      medication were assessed for 24 h after anaesthesia. Multivariate logistic
      regression analysis was performed to quantify risk factors for PONV and need for
      rescue medication. RESULTS: Four hundred and eighty-eight subjects were available
      for the final analysis. The incidence of PONV in subjects without prophylaxis was
      lower than expected according to the Apfel Score (28% observed; 42% expected,
      P<0.001). Independent predictors for PONV were (adjusted odds ratio; 95%
      confidence interval) female sex (1.76; 1.08-2.89), younger patient age (0.82 per
      10 yr; 0.69-0.97), and longer duration of anaesthesia (1.36 per hour; 1.17-1.59).
      CONCLUSIONS: The incidence of PONV was significantly lower than predicted by the
      Apfel Score. Female sex, younger age, and longer duration of anaesthesia are risk
      factors for PONV after xenon-based anaesthesia. CLINICAL TRIAL REGISTRATION:
      German Federal Institute for Drugs and Medical Devices number AL-PMS-01/07GER.

PMID- 25962613
TI  - Oxygen availability effect on the performance of air-breathing cathode microbial
      fuel cell.
AB  - The effect of the oxygen availability over the performance of an air-breathing
      microbial fuel cell (MFC) was studied by limiting the oxygen supply to the
      cathode. It was found that anodic reaction was the limiting stage in the
      performance of the MFC while oxygen was fully available at cathode. As the
      cathode was depleted of oxygen, the current density becomes limited by oxygen
      transport to the electrode surface. The exerted current density was maintained
      when oxygen mole fraction was higher than 10% due to the very good performance of
      the cathodic catalysts. However, the current density drastically falls when
      working at lower concentrations because of mass transfer limitations. In this
      sense it must be highlighted that the maximum exerted power, when oxygen mole
      fraction was higher than 10%, was almost three times higher than that obtained
      when oxygen mole fraction was 5%. Regarding to the wastewater treatment, a
      significant decrease in the COD removal was obtained when the MFC performance was
      reduced due to the limited availability of oxygen, which indicates the
      significant role of the electrogenic microorganisms in the COD removal in MFC. In
      addition, the low availability of oxygen at the cathode leads to a lower presence
      of oxygen at the anode, resulting in an increase in the coulombic efficiency.

PMID- 25962614
TI  - The effects of oxygen induced pulmonary vasoconstriction on bedside measurement
      of pulmonary gas exchange.
AB  - In patients with respiratory failure measurements of pulmonary gas exchange are
      of importance. The bedside automatic lung parameter estimator (ALPE) of pulmonary
      gas exchange is based on changes in inspired oxygen (FiO2) assuming that these
      changes do not affect pulmonary circulation. This assumption is investigated in
      this study. Forty-two out of 65 patients undergoing coronary artery bypass
      grafting (CABG) had measurements of mean pulmonary arterial pressure (MPAP),
      cardiac output and pulmonary capillary wedge pressure thus enabling the
      calculation of pulmonary vascular resistance (PVR) at each FiO2 level. The
      research version of ALPE was used and FiO2 was step-wise reduced a median of 0.20
      and ultimately returned towards baseline values, allowing 6-8 min' steady state
      period at each of 4-6 levels before recording the oxygen saturation (SpO2). FiO2
      reduction led to median decrease in SpO2 from 99 to 92 %, an increase in MPAP of
      4 mmHg and an increase in PVR of 36 dyn s cm(-5). Changes were immediately
      reversed on returning FiO2 towards baseline. In this study changes in MPAP and
      PVR are small and immediately reversible consistent with small changes in
      pulmonary gas exchange. This indicates that mild deoxygenation induced pulmonary
      vasoconstriction does not have significant influences on the ALPE parameters in
      patients after CABG.

PMID- 25962615
TI  - Associations between oral complications and days to death in palliative care
      patients.
AB  - PURPOSE: Adverse oral symptoms gradually appear in advanced cancer patients as
      the disease progresses. We retrospectively investigated the associations between
      the incidence of oral problems and the days to death (DTD) in patients receiving
      palliative care. METHODS: The dental assessment sheets and medical charts of 105
      patients who had been admitted into the palliative care unit at our hospital were
      examined. Case data included evaluations of organic and functional oral
      conditions at the time of admission for all patients. The cohort was divided into
      two groups according to the DTD as the short group (<28 days from the time of
      dental assessment until death) and the long group (>=28 days). We compared the
      incidences of organic and functional oral problems between these groups. RESULTS:
      Dry mouth, tongue inflammation, and bleeding spots were significantly more
      frequent in the short group than in the long group (78 vs. 54% for dry mouth, 67
      vs. 46% for tongue inflammation, 35 vs. 14% for bleeding spots, respectively; p <
      0.05). Tongue coating and candidiasis were comparable between the two groups.
      Dysphagia was significantly more common in the short group (43%) than in the long
      group (20%) (p = 0.01), as was assistance with oral health care (76 vs. 50%) (p =
      0.01). CONCLUSIONS: Our findings suggest that, during palliative care, oral
      complications appear more frequently when the DTD period is shorter. These
      symptoms may be useful indicators when deciding on the proper timing of intensive
      oral care intervention to decrease oral problems and pain in terminally ill
      patients.

PMID- 25962616
TI  - Enhanced External Counterpulsation Is Cost-Effective in Reducing Hospital Costs
      in Refractory Angina Patients.
AB  - BACKGROUND: Enhanced external counterpulsation (EECP) is effective in the
      treatment of refractory angina, a condition suffered by 1.7 million Americans.
      Declining cardiovascular mortality and appropriate use criteria may further
      increase this number. HYPOTHESIS: EECP is hypothesized to be cost-effective in
      reducing hospitalizations in refractory angina patients. METHODS: The data used
      in this analysis were collected in phase II of the International EECP Patient
      Registry (IEPR-II). Data were collected on changes in Canadian Cardiovascular
      Society functional class, Duke Activity Status Index, and number of
      hospitalizations in the 6 months prior to EECP and in the 6- and 12-month
      intervals following EECP. Estimates of the changes in annual cost of all-cause
      hospitalization before and after EECP therapy were calculated by the product of
      the differences in hospitalization rates in the 6-month interval before and after
      EECP treatment and estimated hospitalization and physician charges after
      subtracting the average cost of EECP. RESULTS: Data for 1015 patients were
      analyzed. Hospitalization occurred in 55.2% of patients, an average of 1.7 +/-
      1.4 hospitalizations/patient, in the 6-month period before 35 hours of EECP; and
      in 24.4%, an average of 1.4 +/- 1.0 hospitalizations/patient, during the 6- to 12
      month period after EECP. The average hospitalization and physician charge in the
      US was $17,995, and the average EECP cost was $4880, yielding an annual cost
      savings/patient of $17,074. CONCLUSIONS: Treatment of refractory angina patients
      with EECP resulted in improvement in angina and functional class accompanied by a
      sustained reduction in health care costs over 1 year of follow-up.

PMID- 25962617
TI  - Analyzing Structure and Function of Vascularization in Engineered Bone Tissue by
      Video-Rate Intravital Microscopy and 3D Image Processing.
AB  - Vascularization is a key challenge in tissue engineering. Three-dimensional
      structure and microcirculation are two fundamental parameters for evaluating
      vascularization. Microscopic techniques with cellular level resolution, fast
      continuous observation, and robust 3D postimage processing are essential for
      evaluation, but have not been applied previously because of technical
      difficulties. In this study, we report novel video-rate confocal microscopy and
      3D postimage processing techniques to accomplish this goal. In an immune
      deficient mouse model, vascularized bone tissue was successfully engineered using
      human bone marrow mesenchymal stem cells (hMSCs) and human umbilical vein
      endothelial cells (HUVECs) in a poly (D,L-lactide-co-glycolide) (PLGA) scaffold.
      Video-rate (30 FPS) intravital confocal microscopy was applied in vitro and in
      vivo to visualize the vascular structure in the engineered bone and the
      microcirculation of the blood cells. Postimage processing was applied to perform
      3D image reconstruction, by analyzing microvascular networks and calculating
      blood cell viscosity. The 3D volume reconstructed images show that the hMSCs
      served as pericytes stabilizing the microvascular network formed by HUVECs. Using
      orthogonal imaging reconstruction and transparency adjustment, both the vessel
      structure and blood cells within the vessel lumen were visualized. Network
      length, network intersections, and intersection densities were successfully
      computed using our custom-developed software. Viscosity analysis of the blood
      cells provided functional evaluation of the microcirculation. These results show
      that by 8 weeks, the blood vessels in peripheral areas function quite similarly
      to the host vessels. However, the viscosity drops about fourfold where it is only
      0.8 mm away from the host. In summary, we developed novel techniques combining
      intravital microscopy and 3D image processing to analyze the vascularization in
      engineered bone. These techniques have broad applicability for evaluating
      vascularization in other engineered tissues as well.

PMID- 25962618
TI  - Evidence-informed strategies for undergraduate nutrition education: a review.
AB  - This review focuses on evidence-informed strategies to enhance learning in
      undergraduate nutrition education. Here, we describe the general shift in
      undergraduate education from a teacher-centered model of teaching to a student
      centered model and present approaches that have been proposed to address the
      challenges associated with this shift. We further discuss case-based, project
      based, and community-based learning, patient simulation, and virtual clinical
      trials as educational strategies to improve students' critical thinking and
      problem-solving skills; these strategies are well suited to the teaching of
      undergraduate nutrition. The strategies are defined, and we discuss the potential
      benefits to students and how they can be applied specifically to the teaching of
      undergraduate nutrition. Finally, we provide a critical analysis of the
      limitations associated with these techniques and propose several directions for
      future research, including research methodologies that may best evaluate teaching
      strategies in terms of both teaching and learning outcomes. Consideration of
      these evidence-informed strategies is warranted, given their ability to encourage
      students to develop relevant skills that will facilitate their transition beyond
      the university classroom. 

PMID- 25962620
TI  - Current complexity: a tool for assessing the complexity of organic molecules.
AB  - Molecular complexity for a synthetic organic chemist is difficult to define,
      though intuitively known. Despite the importance of this concept, the
      quantitative assessment of complexity within organic chemistry has remained a
      challenge. We report here on the development of an approach for generating a
      unique complexity index, which is reflective of both intrinsic molecular
      complexity and extrinsic synthetic complexity. This index is based on a
      community's perception of complexity, within the context of current technology,
      calculating a molecule's current complexity. Our approach allows for a direct
      comparison between molecules, the analysis of trends within research programs, it
      enables an assessment (and comparison) of new synthetic approaches to known
      molecules and is capable of following a molecule's apparent complexity as it
      changes over time. 

PMID- 25962619
TI  - ADHD-associated dopamine transporter, latrophilin and neurofibromin share a
      dopamine-related locomotor signature in Drosophila.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable
      neuropsychiatric disorder with hyperactivity as one of the hallmarks. Aberrant
      dopamine signaling is thought to be a major theme in ADHD, but how this relates
      to the vast majority of ADHD candidate genes is illusive. Here we report a
      Drosophila dopamine-related locomotor endophenotype that is shared by pan
      neuronal knockdown of orthologs of the ADHD-associated genes Dopamine transporter
      (DAT1) and Latrophilin (LPHN3), and of a gene causing a monogenic disorder with
      frequent ADHD comorbidity: Neurofibromin (NF1). The locomotor signature was not
      found in control models and could be ameliorated by methylphenidate, validating
      its relevance to symptoms of the disorder. The Drosophila ADHD endophenotype can
      be further exploited in high throughput to characterize the growing number of
      candidate genes. It represents an equally useful outcome measure for testing
      chemical compounds to define novel treatment options. 

PMID- 25962621
TI  - Cost-effectiveness of continuous subcutaneous insulin infusion versus multiple
      daily injections of insulin in Type 1 diabetes: a systematic review.
AB  - AIM: Continuous subcutaneous insulin infusion (CSII) is increasingly used in
      clinical practice for the management of selected patients with Type 1 diabetes.
      Several cost-effectiveness studies comparing CSII vs. multiple insulin injections
      (MDI) have been reported. The aim was systematically to review these analyses and
      test the hypothesis that CSII is a cost-effective use of healthcare resources
      across settings. METHODS: A literature review was performed using MEDLINE,
      Cochrane Library and other databases. No time limit or language restrictions were
      applied. After two rounds of screening, 11 cost-effectiveness analyses were
      included in the final review, of which nine used the CORE Diabetes Model. A
      narrative synthesis was conducted and mean cost effectiveness calculated.
      RESULTS: CSII was considered cost-effective vs. MDI in Type 1 diabetes in all 11
      studies in 8 countries, with a mean (95% CI) incremental cost effectiveness ratio
      of ?30 862 (17 997-43 727), US$40 143 (23 409-56 876) per quality-adjusted life
      year (QALY) gained. CSII was associated with improved life expectancy and quality
      adjusted life expectancy (0.4-1.1 QALYs in adults), driven by lower HbA(1c) and
      lower frequency of hypoglycaemic events vs. MDI. CSII was associated with higher
      lifetime direct costs due to higher treatment costs but this was partially offset
      by cost-savings from reduced diabetes-related complications. CONCLUSIONS:
      Published cost-effectiveness analyses show that in Type 1 diabetes CSII is cost
      effective vs. MDI across a number of settings for patients who have poor
      glycaemic control and/or problematic hypoglycaemia on MDI, with cost
      effectiveness highly sensitive to the reduction in HbA1c and hypoglycaemia
      frequency associated with CSII.

PMID- 25962622
TI  - Treatment of headache following triptan failure after successful triptan therapy.
AB  - OPINION STATEMENT: Triptans should remain the first choice in migraine abortive
      treatment. They are not always effective or adequate for specific patients.
      Before declaring a triptan in appropriate for a given patient, the provider ought
      to be analytical about the rationale and especially the use of objective efficacy
      outcome measures and ensure that treatment is prescribed and used appropriately.
      Other ergot derivatives, especially dihydroergotamine, may on one hand share
      common contraindications of triptans but on the other hand can be quite effective
      where triptans failed. Non-steroids are simple, readily available, and overall
      safe, and evidence for their efficacy in migraine is plentiful. Opioid analgesics
      are blatantly overprescribed especially in non-complicated migraine patients.
      These should be used with great care and restraint and closely monitored.
      Frequent opioid usage often leads to tolerance, dependence, and medication
      overuse headache. Neurostimulation is gaining momentum in the armamentarium of
      migraine management but at the present time remains primarily focused on
      prophylaxis, yet abortive use is expected to grow.

PMID- 25962623
TI  - Reconstitution of the targeting of Rab6A to the Golgi apparatus in semi-intact
      HeLa cells: A role of BICD2 in stabilizing Rab6A on Golgi membranes and a
      concerted role of Rab6A/BICD2 interactions in Golgi-to-ER retrograde transport.
AB  - Rab is a small GTP-binding protein family that regulates various pathways of
      vesicular transport. Although more than 60 Rab proteins are targeted to specific
      organelles in mammalian cells, the mechanisms underlying the specificity of Rab
      proteins for the respective organelles remain unknown. In this study, we
      reconstituted the Golgi targeting of Rab6A in streptolysin O (SLO)-permeabilized
      HeLa cells in a cytosol-dependent manner and investigated the biochemical
      requirements of targeting. Golgi-targeting assays identified Bicaudal-D (BICD)2,
      which is reportedly involved in the dynein-mediated transport of mRNAs during
      oogenesis and embryogenesis in Drosophila, as a cytosolic factor for the Golgi
      targeting of Rab6A in SLO-permeabilized HeLa cells. Subsequent immunofluorescence
      analyses indicated decreased amounts of the GTP-bound active form of Rab6 in
      BICD2-knockdown cells. In addition, fluorescence recovery after photobleaching
      (FRAP) analyses revealed that overexpression of the C-terminal region of BICD2
      decreased the exchange rate of GFP-Rab6A between the Golgi membrane and the
      cytosol. Collectively, these results indicated that BICD2 facilitates the binding
      of Rab6A to the Golgi by stabilizing its GTP-bound form. Moreover, several
      analyses of vesicular transport demonstrated that Rab6A and BICD2 play crucial
      roles in Golgi tubule fusion with the endoplasmic reticulum (ER) in brefeldin A
      (BFA)-treated cells, indicating that BICD2 is involved in coat protein I (COPI)
      independent Golgi-to-ER retrograde vesicular transport. 

PMID- 25962624
TI  - Oleic acid enhances the motility of umbilical cord blood derived mesenchymal stem
      cells through EphB2-dependent F-actin formation.
AB  - The role of unsaturated fatty acids (UFAs) is essential for determining stem cell
      functions. Eph/Ephrin interactions are important for regulation of stem cell fate
      and localization within their niche, which is significant for a wide range of
      stem cell behavior. Although oleic acid (OA) and Ephrin receptors (Ephs) have
      critical roles in the maintenance of stem cell functions, interrelation between
      Ephs and OA has not been explored. Therefore, the present study investigated the
      effect of OA-pretreated UCB-MSCs in skin wound-healing and underlying mechanism
      of Eph expression. OA promoted the motility of UCB-MSCs via EphB2 expression. OA
      mediated GPR40 activation leads to Galphaq-dependent PKCalpha phosphorylation. In
      addition, OA-induced phosphorylation of GSK3beta was followed by beta-catenin
      nuclear translocation in UCB-MSCs. Activation of beta-catenin was blocked by PKC
      inhibitors, and OA-induced EphB2 expression was suppressed by beta-cateninsiRNA
      transfection. Of those Rho-GTPases, Rac1 was activated in an EphB2-dependent
      manner. Accordingly, knocking down EphB2 suppressed F-actin expression. In vivo
      skin wound-healing assay revealed that OA-treated UCB-MSCs enhanced skin wound
      repair compared to UCB-MSCs pretreated with EphB2siRNA and OA. In conclusion, we
      showed that OA enhances UCB-MSC motility through EphB2-dependent F-actin
      formation involving PKCalpha/GSK3beta/beta-catenin and Rac1 signaling pathways. 

PMID- 25962625
TI  - Imaging mass spectrometry: Instrumentation, applications, and combination with
      other visualization techniques.
AB  - Imaging Mass Spectrometry (IMS) is strengthening its position as a valuable
      analytical tool. It has unique ability to identify structures and to unravel
      molecular changes that occur in the precisely defined part of the sample. These
      unique features open new possibilities in the field of various aspects of
      biological research. In this review we briefly discuss the main imaging mass
      spectrometry techniques, as well as the nature of biological samples and
      molecules, which might be analyzed by such methodology. Moreover, a novel
      approach, where different analytical techniques might be combined with the
      results of IMS study, is emphasized and discussed. With such a fast development
      of IMS and related methods, we can foresee the promising future of this
      technique.

PMID- 25962626
TI  - Geometric Verification of Dynamic Wave Arc Delivery With the Vero System Using
      Orthogonal X-ray Fluoroscopic Imaging.
AB  - PURPOSE: The purpose of this study was to define an independent verification
      method based on on-board orthogonal fluoroscopy to determine the geometric
      accuracy of synchronized gantry-ring (G/R) rotations during dynamic wave arc
      (DWA) delivery available on the Vero system. METHODS AND MATERIALS: A
      verification method for DWA was developed to calculate O-ring-gantry (G/R)
      positional information from ball-bearing positions retrieved from fluoroscopic
      images of a cubic phantom acquired during DWA delivery. Different noncoplanar
      trajectories were generated in order to investigate the influence of path
      complexity on delivery accuracy. The G/R positions detected from the fluoroscopy
      images (DetPositions) were benchmarked against the G/R angulations retrieved from
      the control points (CP) of the DWA RT plan and the DWA log files recorded by the
      treatment console during DWA delivery (LogActed). The G/R rotational accuracy was
      quantified as the mean absolute deviation +/- standard deviation. The maximum G/R
      absolute deviation was calculated as the maximum 3-dimensional distance between
      the CP and the closest DetPositions. RESULTS: In the CP versus DetPositions
      comparison, an overall mean G/R deviation of 0.13 degrees /0.16 degrees  +/- 0.16
      degrees /0.16 degrees  was obtained, with a maximum G/R deviation of 0.6 degrees
      /0.2 degrees . For the LogActed versus DetPositions evaluation, the overall mean
      deviation was 0.08 degrees /0.15 degrees  +/- 0.10 degrees /0.10 degrees  with a
      maximum G/R of 0.3 degrees /0.4 degrees . The largest decoupled deviations
      registered for gantry and ring were 0.6 degrees  and 0.4 degrees  respectively.
      No directional dependence was observed between clockwise and counterclockwise
      rotations. Doubling the dose resulted in a double number of detected points
      around each CP, and an angular deviation reduction in all cases. CONCLUSIONS: An
      independent geometric quality assurance approach was developed for DWA delivery
      verification and was successfully applied on diverse trajectories. Results showed
      that the Vero system is capable of following complex G/R trajectories with
      maximum deviations during DWA below 0.6 degrees .

PMID- 25962627
TI  - Long-Term Efficacy and Toxicity of Low-Dose-Rate 125I Prostate Brachytherapy as
      Monotherapy in Low-, Intermediate-, and High-Risk Prostate Cancer.
AB  - PURPOSE/OBJECTIVES: To report long-term efficacy and toxicity for a single
      institution cohort of patients treated with low-dose-rate prostate brachytherapy
      permanent implant (PI) monotherapy. METHODS AND MATERIALS: From 1996 to 2007,
      1989 patients with low-risk (61.3%), intermediate-risk (29.8%), high-intermediate
      risk (4.5%), and high-risk prostate cancer (4.4%) were treated with PI and
      followed up prospectively in a registry. All patients were treated with (125)I
      monotherapy to 144 Gy. Late toxicity was coded retrospectively according to a
      modified Common Terminology Criteria for Adverse Events 4.0 scale. The rates of
      biochemical relapse-free survival (bRFS), distant metastasis-free survival
      (DMFS), overall survival (OS), and prostate cancer-specific mortality (PCSM) were
      calculated. We identified factors associated with late grade >=3 genitourinary
      (GU) and gastrointestinal (GI) toxicity, bRFS, DMFS, OS, PCSM, and incontinence.
      RESULTS: The median age of the patients was 67 years, and the median overall and
      prostate-specific antigen follow-up times were 6.8 years and 5.8 years,
      respectively. The overall 5-year rates for bRFS, DMFS, OS, and PCSM were 91.9%,
      97.8%, 93.7%, and 0.71%, respectively. The 10-year rates were 81.5%, 91.5%,
      76.1%, and 2.5%, respectively. The overall rates of late grade >=3 GU and GI
      toxicity were 7.6% and 0.8%, respectively. On multivariable analysis, age and
      prostate length were significantly associated with increased risk of late grade
      >=3 GU toxicity. The risk of incontinence was highly correlated with both pre-PI
      and post-PI transurethral resection of the prostate. CONCLUSIONS: Prostate
      brachytherapy as monotherapy is an effective treatment for low-risk and low
      intermediate-risk prostate cancer and appears promising as a treatment for high
      intermediate-risk and high-risk prostate cancer. Significant long-term toxicities
      are rare when brachytherapy is performed as monotherapy.

PMID- 25962628
TI  - Impact of diurnal temperature range on mortality in a high plateau area in
      southwest China: A time series analysis.
AB  - BACKGROUND: Diurnal temperature range (DTR) is an important meteorological
      indicator that reflects weather stability and is associated with global climate
      change and urbanization. Previous studies have explored the effect of DTR on
      human health in coastal cities with small daily temperature variations, but we
      have little evidence for high plateau regions where large DTRs usually occur.
      Using daily mortality data (2007-2013), we conducted a time-series analysis to
      assess the effect of DTR on daily mortality in Yuxi, a high plateau city in
      southwest China. METHODS: Poisson regression with distributed lag non-linear
      model was used to estimate DTR effects on daily mortality, controlling for daily
      mean temperature, relative humidity, sunshine duration, wind speed, atmospheric
      pressure, day of the week, and seasonal and long-term trends. RESULTS: The
      cumulative effects of DTR were J-shaped curves for non-accidental,
      cardiorespiratory and cardiovascular mortality, with a U-shaped curve for
      respiratory mortality. Risk assessments showed strong monotonic increases in
      mortality starting at a DTR of approximately 16  degrees C. The relative risk of
      non-accidental morality with extreme high DTR at lag 0 and 0-21 days was 1.03
      (95% confidence interval: 0.95-1.11) and 1.33 (0.94-1.89), respectively. The risk
      of mortality with extreme high DTR was greater for males and age <75 years than
      females and age >=75 years. CONCLUSIONS: The effect of DTR on mortality was non
      linear, with high DTR associated with increased mortality. A DTR of 16  degrees C
      may be a cut-off point for mortality prognosis and has implications for
      developing intervention strategies to address high DTR exposure.

PMID- 25962629
TI  - Demodex hominis.

PMID- 25962630
TI  - Unravelling the complex trait of harvest index in rapeseed (Brassica napus L.)
      with association mapping.
AB  - BACKGROUND: Harvest index (HI), the ratio of grain yield to total biomass, is
      considered as a measure of biological success in partitioning assimilated
      photosynthate to the harvestable product. While crop production can be
      dramatically improved by increasing HI, the underlying molecular genetic
      mechanism of HI in rapeseed remains to be shown. RESULTS: In this study, we
      examined the genetic architecture of HI using 35,791 high-throughput single
      nucleotide polymorphisms (SNPs) genotyped by the Illumina BrassicaSNP60 Bead Chip
      in an association panel with 155 accessions. Five traits including plant height
      (PH), branch number (BN), biomass yield per plant (BY), harvest index (HI) and
      seed yield per plant (SY), were phenotyped in four environments. HI was found to
      be strongly positively correlated with SY, but negatively or not strongly
      correlated with PH. Model comparisons revealed that the A-D test (ADGWAS model)
      could perfectly balance false positives and statistical power for HI and
      associated traits. A total of nine SNPs on the C genome were identified to be
      significantly associated with HI, and five of them were identified to be
      simultaneously associated with HI and SY. These nine SNPs explained 3.42% of the
      phenotypic variance in HI. CONCLUSIONS: Our results showed that HI is a complex
      polygenic phenomenon that is strongly influenced by both environmental and
      genotype factors. The implications of these results are that HI can be increased
      by decreasing PH or reducing inefficient transport from pods to seeds in
      rapeseed. The results from this association mapping study can contribute to a
      better understanding of natural variations of HI, and facilitate marker-based
      breeding for HI.

PMID- 25962631
TI  - Robotic transanal total mesorectal excision with intersphincteric dissection for
      extreme distal rectal cancer: a video demonstration.

PMID- 25962632
TI  - Biofeedback therapy for constipation due to dyssynergic defecation: ready for
      prime time.

PMID- 25962633
TI  - Quiet and distortion-free, whole brain BOLD fMRI using T2 -prepared RUFIS.
AB  - PURPOSE: To develop and evaluate a novel MR method that addresses some of the
      most eminent technical challenges of current BOLD-based fMRI in terms of 1)
      acoustic noise and 2) geometric distortions and signal dropouts. METHODS: A BOLD
      sensitive fMRI pulse sequence was designed that first generates T2-weighted
      magnetization (using a T2 preparation module) and subsequently undergoes three
      dimensional (3D) radial encoding using a rotating ultrafast imaging sequence
      (RUFIS). The method was tested on healthy volunteers at 3T with motor, visual,
      and auditory tasks, and compared relative to standard gradient and spin echo
      planar imaging (EPI) methods. RESULTS: In combination with parallel imaging the
      method achieves efficient and robust 3D whole brain coverage (3 mm isotropic
      resolution in 2.65 s scan time). Compared with standard EPI-based fMRI, the
      method demonstrated 1) T2-weighted imaging clean of geometrical distortions and
      signal dropout, 2) an acoustic noise reduction of ~40 dB(A), and 3) a consistent
      BOLD response that is less sensitive (~1.3% BOLD change) but spatially more
      specific. CONCLUSION: T2-prepared RUFIS provides quiet and distortion-free whole
      brain BOLD fMRI with minimal demands on the gradient performance. In particular,
      auditory fMRI and/or studies involving brain regions near air-tissue interfaces
      are expected to greatly benefit from the proposed method, especially if performed
      at ultrahigh field strengths.

PMID- 25962634
TI  - The uneven seepage of science: Diabetes and biosociality in China.
AB  - The rapid growth of the Chinese economy in the post-Mao era has been accompanied
      by a sharp increase in the prevalence of diabetes and recent studies suggest that
      there is now more than a 100 million diabetics in China. This article explores
      how biomedical diabetes treatment contributes to configure subjectivities and
      collectivities in contemporary China. Based on an ethnographic study of
      diabetics, it argues that biomedical knowledge of diabetes is subtly inflected as
      it is transmitted by doctors, pharmaceutical companies, and patients, and that
      these differentiated modes of transmission work against the emergence of a
      singular diabetic subjectivity and biosociality.

PMID- 25962636
TI  - Food selection criteria for disaster response planning in urban societies.
AB  - BACKGROUND: Nutrition professionals that have menu planning and disaster
      management responsibilities should consider factors that have transcended from
      ancient to current times, in addition to recognizing societal trends that have
      led to our current increased vulnerability in the event of a disaster. Hence, we
      proceeded to develop a set of "Disaster Response Diets" (DRDs) for use in urban
      societies inclusive of the aforementioned considerations. METHODS: A three-phase
      multidimensional approach was used to identify food groups suitable for creating
      a set of DRDs. Phase One consisted of calculating the percent daily nutrient
      intake and Drewnowski's naturally nutrient rich (NNR) score for an individual or
      mean composite for one serving of food from 11 specific food groups. In Phase
      Two, in addition to nutrient density, the 11 food groups were evaluated and
      scored based on the following DRD planning criteria: storage and handling
      properties, preparation ease and, cultural acceptance/individual tolerance.
      During Phase Three, three DRDs were developed based upon the data retrieved from
      Phases one and two. RESULTS: In Phase One, the NNR scores ranged from 2.1 for
      fresh fruits to 28.1 for dry cereals, a higher score indicating a higher nutrient
      density. During Phase Two, a maximum score of 12 was possible based on
      appropriateness for a disaster situation. Five plant-based food groups (dry
      cereals, nuts, dried fruits, grains and legumes) achieved a score ranging between
      7 and 12, whereas the five fresh food groups were deemed ineligible due to
      sanitation and perishability concerns. During Phase Three, three DRDs (milk
      inclusive, milk-free and Grab-and-Go) were developed as benchmarks for disaster
      response planning. CONCLUSIONS: Plant-based DRDs are universally acceptable and
      tolerated across cultures and religions. Therefore, we suggest nutrition
      professionals consider using a plant-based approach for creating DRDs for public
      health institutions and organizations.

PMID- 25962637
TI  - What Is the Impact of Online Training in Mind-Body Skills?
AB  - BACKGROUND: Mind-body skills (MBS) training is popular, but in-person training
      can be inconvenient and costly. We assessed the impact of online MBS training on
      clinicians' and trainees' stress, mindfulness, and confidence in providing calm,
      compassionate care. METHODS: This was a prospective cohort trial. Trainees
      entering medical school; graduate programs in nursing, social work, and
      dietetics; and residencies in family medicine and pediatrics at a large
      Midwestern academic health center were invited to complete online surveys before
      and 12 weeks after enrolling in online elective integrative health courses on MBS
      training or not. The elective offered no course credit and had no mandated
      deadlines for completion. RESULTS: At baseline, the 60 who engaged in MBS
      training were similar to the 43 who did not in terms of profession, gender,
      perceived stress levels, mindfulness, resilience, and compassion. MBS
      participants engaged in a median of 3 of 12 available modules with a bimodal
      distribution peaking at 1 to 2 and 12 modules. Twelve weeks later, those who
      participated in MBS showed significantly greater improvements in measures of
      stress, mindfulness, and confidence in providing calm, compassionate care than
      those who did not. CONCLUSIONS: Online elective training offers a feasible
      strategy to improve mindfulness, stress, and confidence in providing calm,
      compassionate care. Additional studies are needed to determine the impact of
      required versus elective courses, the optimal dosage and content of training, and
      the costs and benefits of online versus in-person training.

PMID- 25962635
TI  - Brain tumor is a sequence-specific RNA-binding protein that directs maternal mRNA
      clearance during the Drosophila maternal-to-zygotic transition.
AB  - BACKGROUND: Brain tumor (BRAT) is a Drosophila member of the TRIM-NHL protein
      family. This family is conserved among metazoans and its members function as post
      transcriptional regulators. BRAT was thought to be recruited to mRNAs indirectly
      through interaction with the RNA-binding protein Pumilio (PUM). However, it has
      recently been demonstrated that BRAT directly binds to RNA. The precise sequence
      recognized by BRAT, the extent of BRAT-mediated regulation, and the exact roles
      of PUM and BRAT in post-transcriptional regulation are unknown. RESULTS: Genome
      wide identification of transcripts associated with BRAT or with PUM in Drosophila
      embryos shows that they bind largely non-overlapping sets of mRNAs. BRAT binds
      mRNAs that encode proteins associated with a variety of functions, many of which
      are distinct from those implemented by PUM-associated transcripts. Computational
      analysis of in vitro and in vivo data identified a novel RNA motif recognized by
      BRAT that confers BRAT-mediated regulation in tissue culture cells. The
      regulatory status of BRAT-associated mRNAs suggests a prominent role for BRAT in
      post-transcriptional regulation, including a previously unidentified role in
      transcript degradation. Transcriptomic analysis of embryos lacking functional
      BRAT reveals an important role in mediating the decay of hundreds of maternal
      mRNAs during the maternal-to-zygotic transition. CONCLUSIONS: Our results
      represent the first genome-wide analysis of the mRNAs associated with a TRIM-NHL
      protein and the first identification of an RNA motif bound by this protein
      family. BRAT is a prominent post-transcriptional regulator in the early embryo
      through mechanisms that are largely independent of PUM.

PMID- 25962638
TI  - Butein suppresses cervical cancer growth through the PI3K/AKT/mTOR pathway.
AB  - Cervical cancer is the second most common women carcinoma worldwide and the
      fourth leading cause of cancer-associated mortality in women. Butein, a bioactive
      flavonoid isolated from numerous native plants, has been shown to induce
      apoptosis and inhibits migration and invasion in numerous human cancer cells.
      However, to the best of our knowledge, the effect of butein on human cervical
      cancer cells has not been reported. The present study aimed to determine the
      effect of butein on cell growth, apoptosis, migration and invasion and identify
      the associated molecular mechanism involved using HeLa human cervical cancer
      cells in vitro, and on tumor growth in a nude mouse model. It was found that
      butein notably inhibited cell viability, colony formation, migration and
      invasion, induced cell cycle at the G2/M stage and cell apoptosis, as well as
      enhanced caspase-3, -8 and -9 activity in HeLa cells in a dose-dependent manner.
      When administered intraperitoneally, butein inhibited the tumor growth of human
      cervical cancer xenograft tumors in the nude mouse model. Additionally, treatment
      with butein significantly increased reactive oxygen species (ROS) generation and
      reduced the phosphorylation of PI3K, AKT and mTOR expression, which contributes
      to the inhibition of the tumor growth of cervical cancer and reduction of
      oxidative stress. These findings suggested that butein serves as a potential
      therapeutic agent for the treatment of cervical cancer.

PMID- 25962639
TI  - Ataxia induced by a thymic neuroblastoma in the elderly patient.
AB  - Thymic neuroblastoma is a rare tumor with only few reports in modern literature.
      Whereas most data is taken from childhood neuroblastoma, little is known about
      the characteristics of the disease in the adult and elderly population. There are
      significant differences between adult and childhood neuroblastoma which are
      reviewed below. We report a case of a 62-year-old male who presented with
      neurological symptoms of ataxia and opsoclonus and an anterior mediastinal mass.
      Ultimately, the patient underwent a resection of the mass and pathologic review
      identified a thymic neuroblastoma. This is the first case of thymic neuroblastoma
      associated with symptomatic central nervous system disease; it is presented with
      an up-to-date review of the previous cases in the field as well with a review of
      the literature of post adolescent neuroblastoma.

PMID- 25962640
TI  - Conjugated Linoleic Acid and Postmenopausal Women's Health.
AB  - Declined estrogen levels in women after menopause can cause a number of
      significant health issues, and various estrogen receptor ligands have been
      clinically evaluated for postmenopausal treatment. Conjugated linoleic acid (CLA)
      has been shown to display protective effects against menopausal symptoms such as
      bone loss and metabolic dysfunctions in both animals and humans. In particular,
      it inhibits the proliferations of breast and endometrial cancer cells through
      estrogen receptor alpha-mediated mechanism(s). These findings suggest that CLA
      may provide beneficial effects on menopausal symptoms, while protecting the
      endometrium and breast from estrogen stimulation. Thus, understanding the effects
      of CLA on menopausal disorders and ER metabolism is important in development of
      novel therapeutic options for use in postmenopausal women with or without
      conventional estrogen therapy. In this report, we review literature regarding the
      impact of CLA on menopausal symptoms in cell lines, rodents, and humans, along
      with potential mechanism(s). We also discuss safety consideration for CLA use in
      humans. 

PMID- 25962641
TI  - T-2 toxin inhibits gene expression and activity of key steroidogenesis enzymes in
      mouse Leydig cells.
AB  - T-2 toxin is one of the mycotoxins, a group of type A trichothecenes produced by
      several fungal genera including Fusarium species, which may lead to the decrease
      of the testosterone secretion in the primary Leydig cells derived from the mouse
      testis. The previous study demonstrated the effects of T-2 toxin through direct
      decrease of the testosterone biosynthesis in the primary Leydig cells derived
      from the mouse testis. In this study, we further examined the direct biological
      effects of T-2 toxin on steroidogenesis production, primarily in Leydig cells of
      mice. Mature mouse Leydig cells were purified by Percoll gradient centrifugation
      and the cell purity was determined by 3beta-hydroxysteroid dehydrogenase (3beta
      HSD) staining. To examine T-2 toxin-induced testosterone secretion decrease, we
      measured the transcription levels of 3 key steroidogenic enzymes and 5 enzyme
      activities including 3beta-HSD-1, P450scc, StAR, CYP17A1, and 17beta-HSD in T-2
      toxin/human chorionicgonadotropin (hCG) co-treated cells. Our previous study
      showed that T-2 toxin (10(-7) M, 10(-8) M and 10(-9) M) significantly suppressed
      hCG (10 ng/ml)-induced testosterone secretion. The studies demonstrated that the
      suppressive effect is correlated with the decreases in the levels of
      transcription of 3beta-HSD-1, P450scc, and StAR (P<0.05) and also in enzyme
      activities of 3beta-HSD-1, P450scc, StAR, CYP17A1, and 17beta-HSD (P<0.05).

PMID- 25962642
TI  - Mechanism of neutrophil activation and toxicity elicited by engineered
      nanomaterials.
AB  - The effects of nanomaterials (NMs) on biological systems, especially their
      ability to stimulate inflammatory responses requires urgent investigation. We
      evaluated the response of the human differentiated HL60 neutrophil-like cell line
      to NMs. It was hypothesised that NM physico-chemical characteristics would
      influence cell responsiveness by altering intracellular Ca2+ concentration
      [Ca2+]i and reactive oxygen species production. Cells were exposed (1.95-125
      MUg/ml, 24 h) to silver (Ag), zinc oxide (ZnO), titanium dioxide (TiO2), multi
      walled carbon nanotubes (MWCNTs) or ultrafine carbon black (ufCB) and
      cytotoxicity assessed (alamar blue assay). Relatively low (TiO2, MWCNTs, ufCB) or
      high (Ag, ZnO) cytotoxicity NMs were identified. Sub-lethal impacts of NMs on
      cell function were investigated for selected NMs only, namely TiO2, Ag and ufCB.
      Only Ag stimulated cell activation. Within minutes, Ag stimulated an increase in
      [Ca2+]i (in Fura-2 loaded cells), and a prominent inward ion current (assessed by
      electrophysiology). Within 2-4 h, Ag increased superoxide anion release and
      stimulated cytokine production (MCP-1, IL-8) that was diminished by Ca2+
      inhibitors or trolox. Light microscopy demonstrated that cells had an activated
      phenotype. In conclusion NM toxicity was ranked; Ag>ufCB>TiO2, and the battery of
      tests used provided insight into the mechanism of action of NM toxicity to guide
      future testing strategies.

PMID- 25962643
TI  - Designing BRET-based conformational biosensors for G protein-coupled receptors.
AB  - Ligand-biased signaling is starting to have significant impact on drug discovery
      programs in the pharmaceutical industry and has reinvigorated our understanding
      of pharmacological efficacy. As such, many investigators and screening campaigns
      are now being directed at a larger section of the signaling responses downstream
      of an individual G protein-coupled receptor. Many biosensor-based platforms have
      been developed to capture signaling signatures. Despite our growing ability to
      use such signaling signatures, we remain hampered by the fact that signaling
      signatures may be particular to an individual cell type and thus our platforms
      may not be portable from cell to cell, necessitating further cell-specific
      biosensor development. Here, we provide a complementary strategy based on
      capturing receptor-proximal conformational profiles using intra-molecular BRET
      based sensors composed of a Renilla luciferase donor engineered into the carboxy
      terminus and CCPGCC motifs which bind fluorescent hairpin arsenical dyes
      engineered into different positions in intracellular loop 3 of FP, the receptor
      for PGF2alpha. We discuss the design and optimization of such sensors for
      orthosteric and allosteric ligands. 

PMID- 25962644
TI  - Post-processing strategies in image scanning microscopy.
AB  - Image scanning microscopy (ISM) coupled with pixel reassignment offers a
      resolution improvement of ?2 over standard widefield imaging. By scanning point
      wise across the specimen and capturing an image of the fluorescent signal
      generated at each scan position, additional information about specimen structure
      is recorded and the highest accessible spatial frequency is doubled. Pixel
      reassignment can be achieved optically in real time or computationally a
      posteriori and is frequently combined with the use of a physical or digital
      pinhole to reject out of focus light. Here, we simulate an ISM dataset using a
      test image and apply standard and non-standard processing methods to address
      problems typically encountered in computational pixel reassignment and pinholing.
      We demonstrate that the predicted improvement in resolution is achieved by
      applying standard pixel reassignment to a simulated dataset and explore the
      effect of realistic displacements between the reference and true excitation
      positions. By identifying the position of the detected fluorescence maximum using
      localisation software and centring the digital pinhole on this co-ordinate before
      scaling around translated excitation positions, we can recover signal that would
      otherwise be degraded by the use of a pinhole aligned to an inaccurate excitation
      reference. This strategy is demonstrated using experimental data from a
      multiphoton ISM instrument. Finally we investigate the effect that imaging
      through tissue has on the positions of excitation foci at depth and observe a
      global scaling with respect to the applied reference grid. Using simulated and
      experimental data we explore the impact of a globally scaled reference on the ISM
      image and, by pinholing around the detected maxima, recover the signal across the
      whole field of view. 

PMID- 25962645
TI  - Variable expression levels of keratin and vimentin reveal differential EMT status
      of circulating tumor cells and correlation with clinical characteristics and
      outcome of patients with metastatic breast cancer.
AB  - BACKGROUND: CTCs expressing variable levels of epithelial and mesenchymal markers
      in breast cancer have previously been reported. However, no information exists
      for keratin expression levels of CTCs in association with disease status, whereas
      assays for the characterization of transitional EMT phenotypes of CTCs in breast
      cancer are rather lacking. We investigated the correlation between keratin
      expression of CTCs and patients' outcome and characterized the EMT status of CTCs
      via the establishment of a numerical "ratio" value of keratin and vimentin
      expression levels on a single cell basis. METHODS: Keratin expression was
      evaluated in 1262 CTCs from 61 CTC-positive patients with metastatic breast
      cancer, using analysis of images obtained through the CellSearch System. For the
      determination of vimentin/keratin (vim/K) ratios, expression levels of keratin
      and vimentin were measured in cytospin preparations of luminal (MCF-7 and T47D)
      and basal (MDA.MB231 and Hs578T) breast cancer cell lines and 110 CTCs from 5 CTC
      positive patients using triple immunofluorescence laser scanning microscopy and
      image analysis. RESULTS: MCF-7 and T47D displayed lower vim/K ratios compared to
      MDA.MB231 and Hs578T cells, while MCF-7 cells that had experimentally undergone
      EMT were characterized by varying intermediate vim/K ratios. CTCs were consisted
      of an heterogeneous population presenting variable vim/K values with 46% of them
      being in the range of luminal breast cancer cell lines. Keratin expression levels
      of CTCs detected by the CellSearch System correlated with triple negative (p =
      0.039) and ER-negative (p = 0.025) breast cancer, and overall survival (p =
      0.038). CONCLUSIONS: Keratin expression levels of CTCs correlate with tumor
      characteristics and clinical outcome. Moreover, CTCs display significant
      heterogeneity in terms of the degree of EMT phenotype that probably reflects
      differential invasive potential. The assessment of the vim/K ratios as a
      surrogate marker for the EMT status of CTCs merits further investigation as a
      prognostic tool in breast cancer.

PMID- 25962647
TI  - Reply to correspondence regarding the paper "Ternesten-Hasseus E, Johansson EL,
      Millqvist E. Cough reduction using capsaicin. Respir Med. 2015 Jan;109(1):27
      37.".

PMID- 25962646
TI  - Epithelial cell identity in hyperplastic precursors of breast cancer.
AB  - INTRODUCTION: In the adult human breast, hyperplastic enlarged lobular unit
      (HELU) and atypical ductal hyperplasia (ADH) are two common abnormalities that
      frequently coexist with ductal carcinoma in situ (DCIS). For this reason, they
      have been proposed as the early steps in a biological continuum toward breast
      cancer. METHODS: We investigated in silico the expression of 369 genes
      experimentally recognized as involved in establishing and maintaining epithelial
      cell identity and mammary gland remodeling, in HELUs or ADHs with respect to the
      corresponding patient-matched normal tissue. RESULTS: Despite the common luminal
      origin, HELUs and ADHs proved to be characterized by distinct gene profiles that
      overlap for 5 genes only. While HELUs were associated with the overexpression of
      progesterone receptor (PGR), ADHs were characterized by the overexpression of
      estrogen receptor 1 (ESR1) coupled with the overexpression of some proliferation
      associated genes. CONCLUSIONS: This unexpected finding contradicts the notion
      that in differentiated luminal cells the expression of estrogen receptor (ER) is
      dissociated from cell proliferation and suggests that the establishing of an ER
      dependent signaling is able to sustain cell proliferation in an autocrine manner
      as an early event in tumor initiation. Although clinical evidence indicates that
      only a fraction of HELUs and ADHs evolve to invasive cancer, present findings
      warn that exposure to synthetic progestins, frequently administered as hormone
      replacement therapy, and estrogens, when abnormally produced by adipose cells and
      persistently present in the stroma surrounding the mammary gland, may cause these
      hyperplastic lesions.

PMID- 25962648
TI  - Lung function impairment increases with age of diagnosis in adult onset asthma.
AB  - BACKGROUND: Asthma-onset in older individuals has been associated with an
      accelerated decline in lung function, but direct comparisons with younger adults
      have not been reported. METHODS: In a random population sample comprising 4983
      individuals from the Copenhagen City Heart Study without asthma at baseline, we
      compared young (<35 years), middle-aged (35-64 years) and older (>64 years)
      adults with newly diagnosed asthma during a 10-year follow-up. RESULTS: The
      proportion of cases with newly diagnosed asthma during follow-up was similar
      across age groups (Older adults: 7% (84/1168), middle-aged adults: 7% (223/3147),
      and young adults: 6% (42/668) (p = ns)). In all three age groups, lung function
      was reduced at baseline in subjects who were subsequently diagnosed with asthma,
      but most pronounced in those >35 years. (Mean FEV1%: Young 90.2% (+/-13.9),
      middle-aged 80.8% (+/-20.8), and older adults 80.8% (+/-24.2), p < 0.001).
      Furthermore, incident asthma was associated with an accelerated decline in lung
      function in older adults (young adults 11.0 mL/year, middle-aged adults 18.2
      mL/year, and older adults 30.8 mL/year). These differences were independent of
      FEV1 at baseline and smoking status, and were not explained by undiagnosed asthma
      in older adults, as the frequency of respiratory symptoms, including wheeze, was
      similar in all three age groups at baseline. CONCLUSIONS: Asthma was diagnosed as
      frequently in older as in younger adults. Preexisting symptoms were equally
      common, but lung function was more reduced pre-diagnosis, and declined more
      rapidly in older adults. This emphasizes the need for a high level of therapeutic
      attention in patients with asthma diagnosed late in life.

PMID- 25962650
TI  - Solar-Energy-Driven Photoelectrochemical Biosensing Using TiO2 Nanowires.
AB  - Photoelectrochemical sensing represents a unique means for chemical and
      biological detection, with foci of optimizing semiconductor composition and
      electronic structures, surface functionalization layers, and chemical detection
      methods. Here, we have briefly discussed our recent developments of TiO2 nanowire
      based photoelectrochemical sensing, with particular emphasis on three main
      detection mechanisms and corresponding examples. We have also demonstrated the
      use of the photoelectrochemical sensing of real-time molecular reaction kinetic
      measurements, as well as direct interfacing of living cells and probing of
      cellular functions. 

PMID- 25962649
TI  - Efficacy of pirfenidone for idiopathic pulmonary fibrosis: An Italian real life
      study.
AB  - BACKGROUND: In this retrospective Italian study, which involved all major
      national interstitial lung diseases centers, we evaluated the effect of
      pirfenidone on disease progression in patients with IPF. METHODS: We
      retrospectively studied 128 patients diagnosed with mild, moderate or severe IPF,
      and the decline in lung function monitored during the one-year treatment with
      pirfenidone was compared with the decline measured during the one-year pre
      treatment period. RESULTS: At baseline (first pirfenidone prescription), the mean
      percentage forced vital capacity (FVC) was 75% (35-143%) of predicted, and the
      mean percentage diffuse lung capacity (DLCO) was 47% (17-120%) of predicted.
      Forty-eight patients (37.5%) had mild disease (GAP index stage I), 64 patients
      (50%) had moderate IPF (stage II), and 8 patients (6.3%) had severe disease
      (stage III). In the whole population, pirfenidone attenuated the decline in FVC
      (p = 0.065), but did not influence the decline in DLCO (p = 0.355) in comparison
      to the pre-treatment period. Stratification of patients into mild and severe
      disease groups based on %FVC level at baseline (>75% and <=75%) revealed that
      attenuation of decline in FVC (p = 0.002) was more pronounced in second group of
      patients. Stratification of patients according to GAP index at baseline (stage I
      vs. II/III) also revealed that attenuation of decline in lung function was more
      pronounced in patients with more severe disease. CONCLUSIONS: In this national
      experience, pirfenidone reduced the rate of annual FVC decline (p = 0.065). Since
      pirfenidone provided significant treatment benefit for patients with moderate
      severe disease, our results suggest that the drug may also be effective in
      patients with more advanced disease.

PMID- 25962651
TI  - A web based cross-platform application for teleconsultation in radiology.
AB  - The growing complexity of radiologic examinations and interventional procedures
      requires frequent exchange of knowledge. Consequently a simple way to share and
      discuss patient images between radiology experts and with colleagues from other
      medical disciplines is needed. Aims of this work were the development and initial
      performance evaluation of a fast and user friendly, platform independent
      teleconsultation system for medical imaging. A local back end system receives
      DICOM images and generates anonymized JPEG files that are uploaded to an internet
      webserver. The front end running on that webserver comprises an image viewer with
      a specially developed pointer element for indicating findings to collaborative
      partners. The front end that uses only standard web technologies works on a
      variety of different platforms, mobile devices and desktop computers. Images can
      be accessed by simply calling up a special internet address in a web browser that
      may be exchanged between users (e.g. via email). A speed evaluation of the system
      showed good results: For example the preparation and upload of a standard head CT
      took less than 21 seconds. The data volume of the same series and the viewer
      application could be transferred to a mobile phone in less than 42 seconds via a
      UMTS network or in less than 3 seconds via a HSPA network. The presented system
      with its minimal hard- and software requirements, its simplicity and platform
      independence might be a promising tool in the increasingly important area of
      teleconsultation. 

PMID- 25962652
TI  - Telephone-based low intensity therapy after crisis presentations to the emergency
      department is associated with improved outcomes.
AB  - INTRODUCTION: In Australia there is an overwhelming need to provide effective
      treatment to patients presenting to the Emergency Department (ED) in mental
      health crisis. We adapted Improving Access to Psychological Therapies service
      model (IAPT) from the National Health Service (NHS) method for the large scale
      delivery of psychological therapies throughout the United Kingdom to an
      Australian ED setting. This telephone-based low intensity therapy was provided to
      people presenting in crisis to the EDs with combinations of anxiety, depression,
      substance use, and suicidal thinking. METHODS: This uncontrolled study utilised
      session-by-session, before-and-after measures of anxiety and depression via
      Patient Health Questionnaire (PHQ-9) and Generalised Anxiety Disorder-7 (GAD-7).
      RESULTS: Of 347 eligible post-crisis ED referred patients, 291 (83.9%) engaged
      with the IAPT team. Most patients (65%) had attended the ED previously on an
      average of 3.9 (SD = 6.0) occasions. Two hundred and forty one patients received
      an average of 4.1 (SD = 2.3) contacts of low-intensity psychological therapies
      including 1.2 (SD = 1.7) community outreach visits between 20th Oct 2011 and 31st
      Dec 2012. Treated patients reported clinically significant improvements in
      anxiety, depression and suicidal ideation. Uncontrolled effect sizes were
      moderate for anxiety (0.6) and depression (0.6). DISCUSSION: The Australian ED
      IAPT program demonstrated that the UK IAPT program could be adapted for emergency
      mental health patients and be associated with similar clinical benefits as the
      original program. FUNDING: The Flinders Medical Centre IAPT program received
      Emergency Department project funding from the Australian Commonwealth Government
      through the Council of Australian Governments (COAG) and the South Australian
      Government initiative, Every Patient Every Service (EPES).

PMID- 25962653
TI  - Post t-PA transfer to hub improves outcome of moderate to severe ischemic stroke
      patients.
AB  - BACKGROUND AND PURPOSE: Telemedicine offers rural hospitals the ability to treat
      acute ischemic stroke on site with intravenous tissue plasminogen activator (t
      PA). Most patients are subsequently transferred to a hub hospital with a primary
      stroke center for post t-PA care. There is little evidence that such transfer is
      beneficial. The purpose of our study is to determine whether the transfer of
      patients to hub hospitals is beneficial. METHODS: We retrospectively analyzed
      data from our prospectively collected cohort in the AR SAVES (Stroke Assistance
      through Virtual Emergency Support) telestroke network from November 2008 till
      January 2012. We compared the outcome of patients who were transferred to a "hub"
      with those who remained at the "spoke" hospital where thrombolysis took place. We
      stratified patients according to stroke severity using admission NIHSS scores
      into two groups: patients with mild stroke (NIHSS <8) and those with moderate to
      severe stroke (NIHSS >=8). We defined good outcome as a modified Rankin Scale
      (mRS) score <=2. Statistical analysis was performed using Fisher's exact test,
      two-tailed, and significance was considered at p < 0.05. RESULTS: Out of 894
      telestroke consultations, 206 patients received thrombolytic therapy; 134
      patients had moderate to severe strokes and 160 patients (78%) were transferred
      to the hub after thrombolytic therapy. The percentage of patients with good
      outcome at 3 months was similar between patients transferred to hub and those who
      stayed at the spoke (61% vs. 55%, p = NS). However, when only patients with
      moderate to severe strokes were analyzed, patients transferred to the hub were
      more likely to have good outcomes at three months post t-PA (50% versus 24%, p =
      0.026). CONCLUSIONS: Patients with moderate to severe ischemic strokes who were
      treated with t-PA in a telestroke network may potentially benefit from expert
      care at a primary stroke center.

PMID- 25962654
TI  - Telehealth on heart failure: results of the Recap project.
AB  - Telehealth has become a very important tool that allows the monitoring of heart
      failure patients in a home environment. However, little is known about the effect
      that such monitoring systems have on patients' compliance, evolution and self
      care behaviour. In particular, the effect that the selected user interface has on
      these factors is unknown. This study aims to investigate this, and to determine
      some practicalities that must be considered when designing and implementing a
      telehealth programme for heart failure. To achieve this, daily measurements of
      blood pressure, pulse, SpO2 and weight were collected from 534 patients suffering
      from heart failure. In addition, they were asked to fill in the European heart
      failure self-care behaviour scale questionnaire and the EQ-5D quality of life
      questionnaire, before and after the monitoring period. Two telehealth systems
      were used, the Motiva platform provided by Philips and the standalone unit
      provided by Docobo, the Doc@Home system. Significant differences were found
      between both systems concerning the compliance and adherence of patients.
      Moreover, a general, positive effect of telehealth was identified due to the fact
      that patients showed an increased self-awareness when managing their condition.
      These findings are supported by behavioural changes and a better understanding of
      heart failure from the patients' perspective. 

PMID- 25962655
TI  - The critical roles of tumor-initiating cells and the lymph node stromal
      microenvironment in human colorectal cancer extranodal metastasis using a unique
      humanized orthotopic mouse model.
AB  - Colorectal cancer (CRC) is the second-most common cause of cancer-related
      mortality. The most important prognostic factors are lymph node (LN) involvement
      and extranodal metastasis. Our objective is to investigate the interactions
      between CD133(+)CXCR4(+) (CXC receptor 4) colorectal cancer tumor-initiating
      cells (Co-TICs) and the LN stromal microenvironment in human CRC extranodal
      metastasis. We established a unique humanized orthotopic xenograft model.
      Luciferase-tagged CRC cell lines and human cancer cells were injected
      intrarectally into nonobese diabetic/SCID mice. Mesenteric LN stromal cells,
      stromal cell line HK, or CXCL12 knockdown HK (HK-KD-A3) cells were coinoculated
      with CRC cells. Tumor growth and metastasis were monitored by bioluminescent
      imaging and immunohistochemistry. We found that this model mimics the human CRC
      metastatic pattern with CRC cell lines or patient specimens. Adding LN stromal
      cells promotes CRC tumor growth and extranodal metastasis (P < 0.001). Knocking
      down CXCL12 impaired HK cell support of CRC tumor formation and extranodal
      metastasis. When HK cells were added, sorted CD133(+)CXCR4(+) Co-TICs showed
      increased tumor formation and extranodal metastasis capacities compared to
      unseparated and non-Co-TIC populations. In conclusion, both Co-TIC and LN stromal
      factors play crucial roles in CRC metastasis through the CXCL12/CXCR4 axis.
      Blocking Co-TIC/LN-stromal interactions may lead to effective therapy to prevent
      extranodal metastasis.

PMID- 25962656
TI  - Incidences and outcomes of status epilepticus: A 9-year longitudinal national
      study.
AB  - INTRODUCTION: The national database of status epilepticus (SE) in Thailand is
      limited in terms of the characteristics of the demographics, outcome, and
      prognostic factors. MATERIALS AND METHODS: We retrospectively explored national
      data in Thailand for reimbursement of all adult patients with SE admitted in the
      fiscal year 2004-2012. Patients with SE were diagnosed and searched based on ICD
      10 (G41) from the national database of the Universal Health Coverage Insurance
      office. RESULTS: There were 12,367 patients with SE. The average age was 48.14
      years, and 8119 patients were males (65.7%). At discharge, 75.2% of patients were
      improved, while 16.4% were not improved, and in-hospital mortality rate was 8.4%.
      The first three most common comorbid conditions were hypertension (1790 patients,
      14.5%), diabetes mellitus (1064 patients, 8.6%), and previous stroke (819
      patients, 6.6%). The common complications were respiratory failure (3990
      patients, 32.3%), pneumonia (1201 patients, 9.7%) and septicemia (876 patients,
      7.1%). The mean (SD) hospital stay was 5.48 (11.44) days. Patients with SE with
      age over 60 years, female patients, and patients at primary care hospitals had
      higher proportions of poor outcomes at 36.1%, 39.6%, and 40.9%. Out of 11
      comorbid conditions, six of them were significantly associated with poor
      outcomes. Additionally, 5 complications and two procedures were significant
      factors of poor outcomes. CONCLUSIONS: Factors associated with poor outcome in
      admitted patients with SE by the national data were age, gender, hospital level,
      comorbid conditions, complications of SE, and procedural intervention. This
      article is part of a Special Issue entitled "Status Epilepticus".

PMID- 25962657
TI  - Perampanel in patients with refractory and super-refractory status epilepticus in
      a neurological intensive care unit.
AB  - INTRODUCTION: In refractory status epilepticus (SE), because of subcellular
      maladaptive changes, GABAergic drugs are no longer effective, and the excitatory
      neurotransmitter glutamate (Glu) plays a major role in seizure perpetuation.
      Perampanel (PER, licensed since 09/2012) is the first orally active
      noncompetitive AMPA receptor antagonist for adjunctive treatment of refractory
      focal epilepsy. METHODS: We analyzed treatment response, seizure outcome, and
      adverse effects of add-on treatment with perampanel in patients with refractory
      status epilepticus in the Neurological Intensive Care Unit (NICU), Salzburg,
      Austria between 09/2012 and 11/2014 by retrospective chart review. RESULTS:
      Twelve patients (75% women) with refractory status epilepticus were treated with
      PER administered per nasogastric tube between 09/2012 and 11/2014. Median age was
      75 years [range: 60-91]. The most frequent SE type was nonconvulsive SE (NCSE)
      with (5/12, 42%) and without coma (6/12, 50%). In seven patients (58%), SE arose
      de novo, with an acute symptomatic cause in five patients (42%). Cerebrovascular
      diseases (4/12, 33%) and cerebral tumors (4/12, 33%) were the most common
      etiologies. Perampanel was given after a median number of four antiepileptic
      drugs [range: 2-7] and a median time of 1.5 days [range: 0.8-18.3]. In one
      patient (8%), clinical improvement was observed within 24h and EEG improvement
      within 60 h after administration of PER, while in another patient (8%), clinical
      and EEG improvement was observed more than 48 h after administration. Median
      initial dose was 4 mg [range: 2-12; SD: 4.11], titrated up to a median of 12 mg
      [range: 4-12] in steps of 2 to 4 mg per day. No adverse effects were reported
      regarding cardiorespiratory changes or laboratory parameters. Outcomes after SE
      were moderate disability in five patients (42%), death in three patients (25%),
      and persistent vegetative state in two patients (17%). CONCLUSION: Though
      glutamate plays a major role in seizure perpetuation, the noncompetitive AMPA
      receptor antagonist PER could only ameliorate seizure activity in a few patients
      with refractory SE. The long duration of SE before the administration of PER via
      nasogastric tube, as well as relatively low doses of PER, might be responsible
      for the modest result. Perampanel was well tolerated, and no adverse events were
      reported. This article is part of a Special Issue entitled Status Epilepticus.

PMID- 25962659
TI  - A novel acquired cryptic three-way translocation t(2;11;5)(p21.3;q13.5;q23.2)
      with a submicroscopic deletion at 11p14.3 in an adult with hypereosinophilic
      syndrome.
AB  - Hypereosinophilic syndrome (HES) is a clinically and pathologically heterogeneous
      disease entity. It is characterized by persistent eosinophilia and organ damage
      after excluding other causes. Clonal eosinophilia is distinguished from
      idiopathic eosinophilia by the presence of histologic, cytogenetic, or molecular
      evidence of an underlying malignancy. There are two distinct subcategories of
      clonal eosinophilia: chronic eosinophilic leukemia, not otherwise specified and
      myeloid/lymphoid neoplasms with eosinophilia and mutations involving platelet
      derived growth factor receptor alpha/beta or fibroblast growth factor receptor 1.
      More than 50% of HES are without knowledge of underlying pathogenic molecular
      pathways. Here we examined a HES patient by oligo-based aCGH analysis and
      molecular cytogenetic methods. Examination for the common eosinophilia-related
      cytogenetic abnormalities involving the genes PDGFRA, PDGFRB, and FGFR1 together
      with BCR-ABL fusion gene was negative. Cytogenetic analysis and multi-color FISH
      analysis revealed a novel cryptic three-way translocation
      t(2;11;5)(p21.3;q13.5;q23.2). By oaCGH analysis we could not find any copy number
      changes related to the cytogenetic breakpoints but instead detected a 0.9Mb
      submicroscopic deletion at 11p14.3. The deleted region involved the 5'-upstream
      sequences and exons 1-4 of the LUZP2 gene, which encodes a leucine zipper
      protein. Analysis of surrogate germ-line cells revealed a normal result showing
      that the detected chromosomal aberrations were acquired. This is the first report
      on a HES patient associated with a novel complex three-way translocation
      t(2;11;5)(p21.3;q13.5;q23.2) and a submicroscopic deletion in chromosome band
      11p14.3. The study also demonstrates the benefits of oligo-based aCGH analysis in
      detecting hidden disease related chromosomal abnormalities. The present findings
      provide additional clues to unravel important molecular pathways in HES to obtain
      the full spectrum of acquired chromosomal and genomic aberrations in this
      heterogeneous disease entity. As more cases become characterized this may
      eventually improve on classification and treatment options.

PMID- 25962658
TI  - Quantitative analysis of the expression of caspase 3 and caspase 9 in different
      types of atherosclerotic lesions in the human aorta.
AB  - The existing data on apoptotic processes in human atherosclerotic lesions is
      insufficient and is often contradictory. This study was undertaken to evaluate
      the levels of the expression of key apoptosis-related genes, namely, caspase 3
      (CASP3) and caspase 9 (CASP9) in the normal (non-atherosclerotic) intima of the
      human aorta in comparison with those in different types of atherosclerotic
      lesions. Twenty-five autopsy samples of thoracic aorta were examined by
      polymerase chain reaction (PCR) analysis. The study revealed that the expressions
      of CASP3 and CASP9 genes were changed in different types of atherosclerotic
      lesions in course of the progression of the disease, but not in a unanimous way.
      The mRNA expression of CASP3 was found to be steadily decreasing with the
      progression of atherosclerosis while the expression of CASP9 showed a pattern
      which can be described as a "bell-shaped" relationship between gene mRNA
      expression and the type of atherosclerotic lesion, with the maximum being
      observed in fatty streaks. The fall in CASP3 expression may be associated with
      cellular senescence as well as with the domination of necrotic processes in
      atherosclerotic lesions, as shown by electron microscopic analysis. Our study
      provides novel quantitative data on the expression of CASP3 and CASP9 genes in
      different atherosclerotic lesions in the human aorta and thus, might assist in
      better understanding of the processes occurring during the development of lesions
      in human atherogenesis.

PMID- 25962660
TI  - [Local allergic reaction post-vaccination against rabies in Argelia].

PMID- 25962661
TI  - [Antimicrobial susceptibility cumulative reports].
AB  - Cumulative reports on antimicrobial susceptibility tests data are important for
      selecting empirical treatments, as an educational tool in programs on
      antimicrobial use, and for establishing breakpoints defining clinical categories.
      These reports should be based on data validated by clinical microbiologists using
      diagnostic samples (not surveillance samples). In order to avoid a bias derived
      from including several isolates obtained from the same patient, it is recommended
      that, for a defined period, only the first isolate is counted. A minimal number
      of isolates per species should be presented: a figure of >=30 isolates is
      statistically acceptable. The report is usually presented in a table format
      where, for each cell, information on clinically relevant microorganisms
      antimicrobial agents is presented. Depending on particular needs, multiple tables
      showing data related to patients, samples, services or special pathogens can be
      prepared. 

PMID- 25962662
TI  - Nitric oxide modulation of endothelium-derived hyperpolarizing factor in agonist
      induced depressor responses in anesthetized rats.
AB  - Vasodilators, such as prostacyclin, nitric oxide (NO), and endothelium-derived
      hyperpolarizing factor (EDHF), released from the vascular endothelium are
      important in the maintenance of systemic blood pressure. Some studies have shown
      that NO affects EDHF-induced vasodilator responses in isolated perfused blood
      vessel segments. However, the effects of NO on EDHF-mediated dilation, and their
      contribution to systemic blood pressure, have not been clarified. Therefore, in
      the present study we investigated the mechanisms underlying acetylcholine- and
      bradykinin-induced depressor responses, as well as the interaction between NO and
      EDHF, by measuring systemic blood pressure in anesthetized rats. In the presence
      of indomethacin and N(G)-nitro-l-arginine (l-NA; an NO synthase inhibitor),
      apamin plus charybdotoxin significantly inhibited depressor responses to
      acetylcholine and bradykinin, whereas glibenclamide, iberiotoxin, quinacrine,
      catalase, and combination of ouabain plus BaCl2 failed to inhibit EDHF-induced
      depressor responses. 4-Aminopyridine significantly inhibited depressor responses
      to acetylcholine, but not to bradykinin. In the presence of indomethacin and l
      NA, carbenoxolone, a gap junction inhibitor, significantly inhibited depressor
      responses to agonists. l-NA alone significantly potentiated agonist-induced
      depressor responses. In contrast, infusion of sodium nitroprusside, an NO donor,
      or 8-br-cGMP significantly inhibited depressor responses to agonist. The findings
      of the present study raise the possibility that agonist-induced depressor
      responses are elicited by propagation of endothelial hyperpolarization via apamin
      plus charybdotoxin-sensitive K(+) channels to smooth muscle cells through gap
      junctions, but not by diffusible substance(s). It is suggested that, in
      anesthetized rats, the EDHF-induced depressor response is attenuated in the
      presence of endogenous and exogenous NO via an increment in cGMP. 

PMID- 25962663
TI  - Proton-induced currents in substantia gelatinosa neurons of the rat trigeminal
      subnucleus caudalis.
AB  - Acid-sensing ion channels (ASICs) are widely expressed in both the peripheral and
      central nervous system, and contribute to the modulation of central nociceptive
      transmission under both physiological and pathophysiological conditions. In this
      study, we characterized the proton-induced membrane currents in acutely isolated
      rat substantia gelatinosa (SG) neurons of the trigeminal subnucleus caudalis
      using the whole cell patch-clamp technique. Exposure to acidic conditions
      (pH<6.5) induced the inward currents in a pH-dependent manner. Amiloride, a
      general ASIC antagonist, significantly blocked the proton-induced currents in a
      non-competitive manner. The pH 6.0-induced membrane current (IpH6.0) was greatly
      attenuated in the Na(+)-free external solution, and the reversal potential of the
      proton-induced currents was similar to the theoretical Na(+) equilibrium
      potential. The IpH6.0 was reciprocally potentiated by a lower extracellular
      Ca(2+) concentration. The modulation of IpH6.0 by divalent cations and other
      modulators suggests that the proton-induced currents are mediated by multiple
      types of ASIC subunits, including ASIC1a and ASIC2a. Multi-cell RT-PCR analysis
      revealed that SG neurons express these subunits. Exposure to a pH 6.0 solution
      directly depolarized the membrane potential, and generated a burst of action
      potentials in a current-clamp mode. This acidic pH-induced depolarization was
      significantly blocked by amiloride. The present results suggest that ASICs
      expressed on SG neurons play important roles in the regulation of nociceptive
      transmission from the orofacial tissues. 

PMID- 25962664
TI  - Hydrogen gas production is associated with reduced interleukin-1beta mRNA in
      peripheral blood after a single dose of acarbose in Japanese type 2 diabetic
      patients.
AB  - Acarbose, an alpha-glucosidase inhibitor, leads to the production of hydrogen
      gas, which reduces oxidative stress. In this study, we examined the effects of a
      single dose of acarbose immediately before a test meal on postprandial hydrogen
      gas in breath and peripheral blood interleukin (IL)-1beta mRNA expression in
      Japanese type 2 diabetic patients. Sixteen Japanese patients (14 men, 2 women)
      participated in this study. The mean+/-standard deviation age, hemoglobin A1c and
      body mass index were 52.1+/-15.4 years, 10.2+/-2.0%, and 27.7+/-8.0kg/m(2),
      respectively. The patients were admitted into our hospital for 2 days and
      underwent test meals at breakfast without (day 1) or with acarbose (day 2). We
      performed continuous glucose monitoring and measured hydrogen gas levels in
      breath, and peripheral blood IL-1beta mRNA levels before (0min) and after the
      test meal (hydrogen gas: 60, 120, 180, and 300min; IL-1beta: 180min). The
      induction of hydrogen gas production and the reduction in peripheral blood IL
      1beta mRNA after the test meal were not significant between days 1 (without
      acarbose) and 2 (with acarbose). However, the changes in total hydrogen gas
      production from day 1 to day 2 were closely and inversely associated with the
      changes in peripheral blood IL-1beta mRNA levels. Our results suggest that an
      increase in hydrogen gas production is inversely associated with a reduction of
      the peripheral blood IL-1beta mRNA level after a single dose of acarbose in
      Japanese type 2 diabetic patients. 

PMID- 25962665
TI  - Protective effects of melatonin against 2,3,7,8-tetrachlorodibenzo-p-dioxin
      induced cardiac injury in rats.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the prototype of a group of highly
      toxic environmental chemicals. Although there are some suggestions regarding TCDD
      induced cardio-toxicity, the exact mechanisms underlying this process have not
      been fully discovered. One mechanism related to this toxicity is believed to be
      the generation of reactive oxygen species. Melatonin is known to be a strong
      antioxidant and has a free radical scavenging ability. Therefore, the aim of this
      study was to investigate the TCDD-induced cardio-toxicity and the protective
      effects of melatonin in rats. Rats were randomly divided into 4 equal groups (n=7
      for each group). Group 1 was control; group 2 was TCDD group (2ug/kg/week, p.o);
      group 3 was melatonin group (5mg/kg/day, i.p.) and group 4 was TCDD and melatonin
      treatment group. All agents were continued to be administered until the 45th day.
      Body/heart weights, mean oxygen saturation (PO2%), hemodynamic [mean blood
      pressure (MBP) and heart rate (HR) from the cannulated-carotid artery] and
      electrocardiographic evaluations (arrhythmias and duration of PR, QRS and QT
      intervals), biochemical and histopathological analysis were carried out. TCDD
      exposure caused significant body and heart weight loss, impairment of PO2%, and
      decrease of MBP and HR levels. Also, major ECG changes and prolongation of PR,
      QRS and QT durations were observed in TCDD-exposed rats. In biochemical analysis,
      TCDD significantly induced lipid peroxidation and reduced antioxidant activities.
      Moreover, our histopathological observations were in accordance with the
      biochemical results. According to the results, melatonin treatment significantly
      protected the subjects from TCDD-induced cardio-toxicity. 

PMID- 25962666
TI  - Processing of Written Irony in Autism Spectrum Disorder: An Eye-Movement Study.
AB  - Previous research has suggested that individuals with Autism Spectrum Disorders
      (ASD) have difficulties understanding others communicative intent and with using
      contextual information to correctly interpret irony. We recorded the eye
      movements of typically developing (TD) adults ASD adults when they read
      statements that could either be interpreted as ironic or non-ironic depending on
      the context of the passage. Participants with ASD performed as well as TD
      controls in their comprehension accuracy for speaker's statements in both ironic
      and non-ironic conditions. Eye movement data showed that for both participant
      groups, total reading times were longer for the critical region containing the
      speaker's statement and a subsequent sentence restating the context in the ironic
      condition compared to the non-ironic condition. The results suggest that more
      effortful processing is required in both ASD and TD participants for ironic
      compared with literal non-ironic statements, and that individuals with ASD were
      able to use contextual information to infer a non-literal interpretation of
      ironic text. Individuals with ASD, however, spent more time overall than TD
      controls rereading the passages, to a similar degree across both ironic and non
      ironic conditions, suggesting that they either take longer to construct a
      coherent discourse representation of the text, or that they take longer to make
      the decision that their representation of the text is reasonable based on their
      knowledge of the world.

PMID- 25962667
TI  - Influence of hydrophobic residues on the binding of CB[7] toward diammonium ions
      of common ammonium...ammonium distance.
AB  - We report the binding constants of CB[7] toward a series of naphthalene
      diammonium and 4,4'-dipiperidinium derivatives and compare the results with those
      obtained previously for CB[7].3b by (1)H NMR and X-ray crystallography. The
      nature of binding in the host.guest complexes was investigated using quantum
      mechanical tools.

PMID- 25962669
TI  - Pathophysiology of primary burning mouth syndrome with special focus on taste
      dysfunction: a review.
AB  - Primary burning mouth syndrome (BMS) is a chronic oral condition characterized by
      burning pain often accompanied with taste dysfunction and xerostomia. The most
      compelling evidence concerning BMS pathophysiology comes from studies on the
      somatosensory system using neurophysiologic or psychophysical methods such as
      blink reflex, thermal quantitative sensory testing, as well as functional brain
      imaging. They have provided convincing evidence for neuropathic involvement at
      several levels of the somatosensory system in BMS pain pathophysiology. The
      number of taste function studies trying to substantiate the subjective taste
      disturbances or studies on salivary factors in BMS is much more limited, and most
      of them suffer from definitional and methodological problems. This review aims to
      critically evaluate the existing literature on the pathophysiology of BMS, paying
      special attention to the correctness of case selection and the methodology used
      in published studies, and to summarize the current state of knowledge. Based on
      the recognition of several gaps in the current understanding of the
      pathophysiology of BMS especially as regards taste and pain system interactions,
      the review ends with future scenarios for research in this area. 

PMID- 25962668
TI  - Micelle-Enhanced Bioorthogonal Labeling of Genetically Encoded Azido Groups on
      the Lipid-Embedded Surface of a GPCR.
AB  - Genetically encoded p-azido-phenylalanine (azF) residues in G protein-coupled
      receptors (GPCRs) can be targeted with dibenzocyclooctyne-modified (DIBO
      modified) fluorescent probes by means of strain-promoted [3+2] azide-alkyne
      cycloaddition (SpAAC). Here we show that azF residues situated on the
      transmembrane surfaces of detergent-solubilized receptors exhibit up to 1000-fold
      rate enhancement relative to azF residues on water-exposed surfaces. We show that
      the amphipathic moment of the labeling reagent, consisting of hydrophobic DIBO
      coupled to hydrophilic Alexa dye, results in strong partitioning of the DIBO
      group into the hydrocarbon core of the detergent micelle and consequently high
      local reactant concentrations. The observed rate constant for the micelleenhanced
      SpAAC is comparable with those of the fastest bioorthogonal labeling reactions
      known. Targeting hydrophobic regions of membrane proteins by use of micelle
      enhanced SpAAC should expand the utility of bioorthogonal labeling strategies. 

PMID- 25962670
TI  - [Multimodality imaging of Langerhans Cell Histiocytosis ].

PMID- 25962671
TI  - Combined Preclinical Magnetic Particle Imaging and Magnetic Resonance Imaging:
      Initial Results in Mice.
AB  - PURPOSE: Magnetic particle imaging (MPI) is a new radiologic imaging modality.
      For the first time, a commercial preclinical scanner is installed. The goal of
      this study was to establish a workflow between MPI and magnetic resonance imaging
      (MRI) scanners for a complete in vivo examination of a mouse and to generate the
      first co-registered in vivo MR-MP images. MATERIALS AND METHODS: The in vivo
      examination of five mice were performed on a preclinical MPI scanner and a 7
      Tesla preclinical MRI system. MRI measurements were used for anatomical
      referencing and validation of the injection of superparamagnetic iron oxide
      (SPIO) particles during a dynamic MPI scan. We extracted MPI data of the
      injection phase and co-registered it with MRI data. RESULTS: A workflow process
      for a combined in vivo MRI and MPI examination was established. A successful
      injection of ferucarbotran was proven in MPI and MRI. MR-MPI co-registration
      allocated the SPIOs in the inferior vena cava and the heart during and shortly
      after the injection. CONCLUSION: The acquisition of preclinical MPI and MRI data
      is feasible and allows the combined analysis of MR-MPI information.

PMID- 25962672
TI  - Impact of Hybrid Iterative Reconstruction on Agatston Coronary Artery Calcium
      Scores in Comparison to Filtered Back Projection in Native Cardiac CT.
AB  - PURPOSE: To investigate whether the effects of hybrid iterative reconstruction
      (HIR) on coronary artery calcium (CAC) measurements using the Agatston score lead
      to changes in assignment of patients to cardiovascular risk groups compared to
      filtered back projection (FBP). MATERIALS AND METHODS: 68 patients (mean age 61.5
      years; 48 male; 20 female) underwent prospectively ECG-gated, non-enhanced,
      cardiac 256-MSCT for coronary calcium scoring. Scanning parameters were as
      follows: Tube voltage, 120 kV; Mean tube current time-product 63.67 mAs (50 - 150
      mAs); collimation, 2 * 128 * 0.625 mm. Images were reconstructed with FBP and
      with HIR at all levels (L1 to L7). Two independent readers measured Agatston
      scores of all reconstructions and assigned patients to cardiovascular risk
      groups. Scores of HIR and FBP reconstructions were correlated (Spearman).
      Interobserver agreement and variability was assessed with K-statistics and Bland
      Altmann-Plots. RESULTS: Agatston scores of HIR reconstructions were closely
      correlated with FBP reconstructions (L1, R = 0.9996; L2, R = 0.9995; L3, R =
      0.9991; L4, R = 0.986; L5, R = 0.9986; L6, R = 0.9987; and L7, R = 0.9986). In
      comparison to FBP, HIR led to reduced Agatston scores between 97 % (L1) and 87.4
      % (L7) of the FBP values. Using HIR iterations L1 - L3, all patients were
      assigned to identical risk groups as after FPB reconstruction. In 5.4 % of
      patients the risk group after HIR with the maximum iteration level was different
      from the group after FBP reconstruction. CONCLUSION: There was an excellent
      correlation of Agatston scores after HIR and FBP with identical risk group
      assignment at levels 1 - 3 for all patients. Hence it appears that the
      application of HIR in routine calcium scoring does not entail any disadvantages.
      Thus, future studies are needed to demonstrate whether HIR is a reliable method
      for reducing radiation dose in coronary calcium scoring.

PMID- 25962673
TI  - xPIPE--Reception of DICOM Data from any Sender via the Internet.
AB  - PURPOSE: Various technologies have been established for DICOM data exchange in
      radiology. In addition to the patient CD, online transfers via VPN (virtual
      private network) or DICOM email are common practice. However, dedicated network
      solutions are generally not appropriate for data exchange with occasional and
      spontaneous partners due to missing infrastructure at the partner institutions
      and/or complex setup procedures. The purpose was to develop a practical solution
      to complement the established technologies to allow users worldwide to transfer
      images without registration. MATERIALS AND METHODS: The development of the xPIPE
      system is based on Java and various software libraries. A client hosted on a
      website enables sending DICOM data to a receiving system of the hospital.
      RESULTS: The new xPIPE system creates a gateway to a receiving hospital which is
      accessible from any point worldwide, giving other hospitals, clinics and patients
      a simple and secure method to transmit DICOM data without intermediate storage on
      external servers. CONCLUSION: The system was deployed at the University Hospital
      Munster and subsequently widely used even without information events and
      training. Data protection during transfer is ensured by the use of signatures and
      encryption. From the user's perspective the system has only minor technical
      requirements and can be used with minimal setup effort.

PMID- 25962676
TI  - [Radyoloji meets Radiology -- three country meeting GAST 2015].

PMID- 25962677
TI  - [Comment on teleradiology - swabs, syringes, radiographic images?].

PMID- 25962678
TI  - [The principles of horizontal division of labor between radiologists and other
      specialists in the current medical malpractice law].

PMID- 25962681
TI  - Demonstrating approaches to chemically modify the surface of Ag nanoparticles in
      order to influence their cytotoxicity and biodistribution after single dose acute
      intravenous administration.
AB  - With the advance in material science and the need to diversify market
      applications, silver nanoparticles (AgNPs) are modified by different surface
      coatings. However, how these surface modifications influence the effects of AgNPs
      on human health is still largely unknown. We have evaluated the uptake, toxicity
      and pharmacokinetics of AgNPs coated with citrate, polyethylene glycol, polyvinyl
      pyrolidone and branched polyethyleneimine (Citrate AgNPs, PEG AgNPs, PVP AgNPs
      and BPEI AgNPs, respectively). Our results demonstrated that the toxicity of
      AgNPs depends on the intracellular localization that was highly dependent on the
      surface charge. BPEI AgNPs (zeta potential = +46.5 mV) induced the highest
      cytotoxicity and DNA fragmentation in Hepa1c1c7. In addition, it showed the
      highest damage to the nucleus of liver cells in the exposed mice, which is
      associated with a high accumulation in liver tissues. The PEG AgNPs (zeta
      potential = -16.2 mV) showed the cytotoxicity, a long blood circulation, as well
      as bioaccumulation in spleen (34.33 ug/g), which suggest better biocompatibility
      compared to the other chemically modified AgNPs. Moreover, the adsorption ability
      with bovine serum albumin revealed that the PEG surface of AgNPs has an optimal
      biological inertia and can effectively resist opsonization or non-specific
      binding to protein in mice. The overall results indicated that the
      biodistribution of AgNPs was significantly dependent on surface chemistry: BPEI
      AgNPs > Citrate AgNPs = PVP AgNPs > PEG AgNPs. This toxicological data could be
      useful in supporting the development of safe AgNPs for consumer products and drug
      delivery applications.

PMID- 25962682
TI  - How important is drinking water exposure for the risks of engineered
      nanoparticles to consumers?
AB  - This study explored the potential for engineered nanoparticles (ENPs) to
      contaminate the UK drinking water supplies and established the significance of
      the drinking water exposure route compared to other routes of human exposure. A
      review of the occurrence and quantities of ENPs in different product types on the
      UK market as well as release scenarios, their possible fate and behaviour in raw
      water and during drinking water treatment was performed. Based on the available
      data, all the ENPs which are likely to reach water sources were identified and
      categorized. Worst case concentrations of ENPs in raw water and treated drinking
      water, using a simple exposure model, were estimated and then qualitatively
      compared to available estimates for human exposure through other routes. A range
      of metal, metal oxide and organic-based ENPs were identified that have the
      potential to contaminate drinking waters. Worst case predicted concentrations in
      drinking waters were in the low- to sub-ug/l range and more realistic estimates
      were tens of ng/l or less. For the majority of product types, human exposure via
      drinking water was predicted to be less important than exposure via other routes.
      The exceptions were some clothing materials, paints and coatings and cleaning
      products containing Ag, Al, TiO2, Fe2O3 ENPs and carbon-based materials. 

PMID- 25962683
TI  - Cytotoxicity of Au, ZnO and SiO2 NPs using in vitro assays with mussel hemocytes
      and gill cells: Relevance of size, shape and additives.
AB  - Metal-bearing nanoparticles (NPs) possess unique physico-chemical characteristics
      that make them useful for an increasing number of industrial products and
      applications, but could also confer them a higher toxicity due to their higher
      reactivity compared to bulk forms of the same materials. There is a considerable
      interest in the use of in vitro techniques in environmentally relevant species,
      such as marine mussels, to evaluate NPs toxicity. In the present work, mussel
      hemocytes and gill cells were used to assess the potential toxic effects of Au,
      ZnO and SiO2 NPs with different sizes and shapes in parallel with their
      respective ionic and bulk forms and additives used in the NPs preparations.
      Cytotoxicity (neutral red and MTT assays) was screened at a wide range of
      concentrations, and LC50 values were calculated. Uptake of fluorescently labeled
      SIO2 NPs of 27 nm by hemocytes was also investigated. Au, ZnO and SiO2 NPs were
      less toxic than the corresponding ionic forms but more toxic than the bulk forms.
      ZnO NPs were the most toxic NPs tested which could be related with their capacity
      to release free ions. SiO2 NPs were not taken up by hemocytes and were not toxic
      to either hemocytes or gill cells. Size-dependent toxicity was found for Au NPs.
      Shape influenced the cytotoxicity of ZnO NPs. Finally, the presence of the
      additives Na-citrate and Ecodis P90 contributed to the toxicity of Au and ZnO
      NPs, respectively. As a general conclusion, solubility appears to play a key role
      in NPs toxicity to mussel cells. 

PMID- 25962679
TI  - New therapeutic targets for cancer bone metastasis.
AB  - Bone metastases are dejected consequences of many types of tumors including
      breast, prostate, lung, kidney, and thyroid cancers. This complicated process
      begins with the successful tumor cell epithelial-mesenchymal transition, escape
      from the original site, and penetration into the circulation. The homing of tumor
      cells to the bone depends on both tumor-intrinsic traits and various molecules
      supplied by the bone metastatic niche. The colonization and growth of cancer
      cells in the osseous environment, which awaken their dormancy to form micro- and
      macro-metastasis, involve an intricate interaction between the circulating tumor
      cells and local bone cells including osteoclasts, osteoblasts, adipocytes, and
      macrophages. We discuss the most recent advances in the identification of new
      molecules and novel mechanisms during each step of bone metastasis that may serve
      as promising therapeutic targets. 

PMID- 25962684
TI  - Role of chemokine CX3CL1 in progression of multiple myeloma via CX3CR1 in bone
      microenvironments.
AB  - Several chemokines/chemokine receptors such as CXCL12, CCL3, CXCR4 and CCR1
      attract multiple myelomas to specific microenvironments. In the present study, we
      investigated whether the CX3CL1/CX3CR1 axis is involved in the interaction of the
      multiple myeloma cells with their microenvironment. The expression of CX3CR1
      (also known as fractalkine) was detected in three of the seven human myeloma cell
      lines. CX3CL1-induced phosphorylation of Akt and ERK1/2 was detected in the
      CX3CR1-positive cell lines, but not in the CX3CR1-negative cell lines. In
      addition, CX3CL1-induced cell adhesion to fibronectin and vascular cell adhesion
      molecule-1 (VCAM-1) in the human myeloma RPMI-8226 cell line. We also
      investigated whether a relationship existed between myeloma cells and osteoclasts
      that may function via the CX3CL1/CX3CR1 axis. Conditioned medium from CX3CL1
      stimulated RPMI-8226 cells drastically increased the osteoclast differentiation.
      Collectively, the results from the present study support the concept of the
      CX3CL1-mediated activation of the progression of the multiple myeloma via CX3CR1.
      Thus, CX3CR1 may represent a potential therapeutic target for the treatment of
      multiple myeloma in a bone microenvironment.

PMID- 25962686
TI  - Focus takes time: structural effects on reading.
AB  - Previous eye-tracking work has yielded inconsistent evidence regarding whether
      readers spend more or less time encoding focused information compared with
      information that is not focused. We report the results of an eye-tracking
      experiment that used syntactic structure to manipulate whether a target word was
      linguistically defocused, neutral, or focused, while controlling for possible
      oculomotor differences across conditions. As the structure of the sentence made
      the target word increasingly more focused, reading times systematically
      increased. We propose that the longer reading times for linguistically focused
      words reflect deeper encoding, which explains previous findings showing that
      readers have better subsequent memory for focused versus defocused information. 

PMID- 25962685
TI  - Negative regulatory roles of DE-ETIOLATED1 in flowering time in Arabidopsis.
AB  - Arabidopsis flowers early under long days (LD) and late under short days (SD).
      The repressor of photomorphogenesis DE-ETIOLATED1 (DET1) delays flowering; det1-1
      mutants flower early, especially under SD, but the molecular mechanism of DET1
      regulation remains unknown. Here we examine the regulatory function of DET1 in
      repression of flowering. Under SD, the det1-1 mutation causes daytime expression
      of FKF1 and CO; however, their altered expression has only a small effect on
      early flowering in det1-1 mutants. Notably, DET1 interacts with GI and binding of
      GI to the FT promoter increases in det1-1 mutants, suggesting that DET1 mainly
      restricts GI function, directly promoting FT expression independent of CO
      expression. Moreover, DET1 interacts with MSI4/FVE, which epigenetically inhibits
      FLC expression, indicating that the lack of FLC expression in det1-1 mutants
      likely involves altered histone modifications at the FLC locus. These data
      demonstrate that DET1 acts in both photoperiod and autonomous pathways to inhibit
      expression of FT and SOC1. Consistent with this, the early flowering of det1-1
      mutants disappears completely in the ft-1 soc1-2 double mutant background. Thus,
      we propose that DET1 is a strong repressor of flowering and has a pivotal role in
      maintaining photoperiod sensitivity in the regulation of flowering time. 

PMID- 25962687
TI  - Forward scanning in verbal working memory updating.
AB  - Effective use of working memory (WM) for high-level cognitive tasks requires
      coordinating two conflicting requirements: robust maintenance and rapid updating.
      Models of WM suggest that these demands are coordinated by a gate between
      perceptual input and WM. Previous work with a letter-updating paradigm (Kessler &
      Oberauer, Journal of Experimental Psychology: Learning, Memory, and Cognition,
      40, 738-754, 2014) supported a scanning and gate-switching (SGS) model of WM
      updating. The present work provides further evidence for the SGS model.
      Participants were required to keep track of the last letter that appeared in each
      of a row of frames on the screen. On each updating step, a variable subset of
      letters in varying positions in the row had to be updated. The SGS model assumes
      that on each updating step, participants scan through the memory set
      sequentially, opening the gate when a letter requires updating, and closing the
      gate when the next letter needs to be maintained. As is predicted by the SGS
      model, the reaction times for each updating step increased with the number of
      updated items and with the number of gate switches. In addition, the present
      experiment provides direct evidence supporting the scanning assumption of the
      model. Hebrew-speaking participants performed the task with either Hebrew or
      English letter stimuli, in different blocks. As was predicted, the scanning
      direction of the stimulus set was from left to right in English and from right to
      left in Hebrew. The SGS model fit the data only when the scanning direction was
      taken into account, establishing the role of item-based forward scanning during
      WM updating. 

PMID- 25962688
TI  - Maintenance of auditory-nonverbal information in working memory.
AB  - According to the multicomponent view of working memory, both auditory-nonverbal
      information and auditory-verbal information are stored in a phonological code and
      are maintained by an articulation-based rehearsal mechanism (Baddeley, 2012). Two
      experiments have been carried out to investigate this hypothesis using sound
      materials that are difficult to label verbally and difficult to articulate.
      Participants were required to maintain 2 to 4 sounds differing in timbre over a
      delay of up to 12 seconds while performing different secondary tasks. While there
      was no convincing evidence for articulatory rehearsal as a main maintenance
      mechanism for auditory-nonverbal information, the results suggest that processes
      similar or identical to auditory imagery might contribute to maintenance. We
      discuss the implications of these results for multicomponent models of working
      memory. 

PMID- 25962689
TI  - Testing drug additivity based on monotherapies.
AB  - Under the Loewe additivity, constant relative potency between two drugs is a
      sufficient condition for the two drugs to be additive. Implicit in this condition
      is that one drug acts like a dilution of the other. Geometrically, it means that
      the dose-response curve of one drug is a copy of another that is shifted
      horizontally by a constant over the log-dose axis. Such phenomenon is often
      referred to as parallelism. Thus, testing drug additivity is equivalent to the
      demonstration of parallelism between two dose-response curves. Current methods
      used for testing parallelism are usually based on significance tests for
      differences between parameters in the dose-response curves of the monotherapies.
      A p-value of less than 0.05 is indicative of non-parallelism. The p-value-based
      methods, however, may be fundamentally flawed because an increase in either
      sample size or precision of the assay used to measure drug effect may result in
      more frequent rejection of parallel lines for a trivial difference. Moreover,
      similarity (difference) between model parameters does not necessarily translate
      into the similarity (difference) between the two response curves. As a result, a
      test may conclude that the model parameters are similar (different), yet there is
      little assurance on the similarity between the two dose-response curves. In this
      paper, we introduce a Bayesian approach to directly test the hypothesis that the
      two drugs have a constant relative potency. An important utility of our proposed
      method is in aiding go/no-go decisions concerning two drug combination studies.
      It is illustrated with both a simulated example and a real-life example.

PMID- 25962690
TI  - Defining Characteristics and Related Factors of Decreased Cardiac Tissue
      Perfusion: Proposal of a New Nursing Diagnosis.
AB  - PURPOSE: To identify the possible defining characteristics (DCs) and related
      factors of the nursing diagnosis (ND) decreased cardiac tissue perfusion.
      METHODS: Cross-sectional study using medical charts of adults admitted to an
      emergency department with the chief complaint of chest pain in a hospital in Sao
      Paulo, Brazil. FINDINGS: DCs identified: crushing chest pain, elevated markers of
      myocardial necrosis, ischemic electrocardiogram changes, sweating, nausea, and
      vomiting. Related factors identified: interruption of arterial blood flow and
      coronary spasm. CONCLUSION: This ND was clinically identified due to significant
      differences in the DCs of patients with and without the diagnosis. PRACTICE
      IMPLICATIONS: The clinical indicators identified in this study can be the
      starting point for the DCs for this ND.

PMID- 25962691
TI  - Effects of tumor necrosis factor-alpha inhibitors in mothers and daughters
      concordant for HLA-B27-positive ankylosing spondylitis.
AB  - OBJECTIVES: Pharmacogenomics is considered as the new frontier to predict the
      response to treatments and it can also be based on the comparison of family
      members being treated for the same condition. No data are available on the impact
      of anti-tumour necrosis factor (TNF)-alpha therapies in members of the same
      family with ankylosing spondylitis (AS). METHODS: We describe three mother
      daughter couples concordant for AS and HLA-B27, both treated with TNF-alpha
      inhibitors, for whom the Bath Ankylosing Spondylitis Disease Activity Index
      (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Ankylosing
      Spondylitis Disease Activity Score (ASDAS)-CRP were evaluated during a follow-up
      of 24 months. RESULTS: All patients manifested improvements of all scores, but
      the daughters had a more prominent effect achieving faster complete disease
      remission. CONCLUSIONS: We hypothesise that longer standing chronic inflammation
      and older age may cause a less prompt and effective response to treatment in SA
      when compared with their genetically related controls.

PMID- 25962692
TI  - Hepatitis B virus screening before adjuvant chemotherapy in patients with early
      stage breast cancer: a cost-effectiveness analysis.
AB  - Most patients with hepatitis B virus (HBV) have no symptoms, and many are unaware
      of the infection. However, HBV can reactivate with immunosuppression;
      chemotherapy causes reactivation in 22 % of hepatitis B surface antigen-positive
      patients. HBV reactivation can be fatal. HBV reactivation can be prevented,
      provided that HBV is recognized prior to chemotherapy. The objective of this
      study is to estimate the health and economic effects of HBV screening strategies
      in patients receiving adjuvant chemotherapy for breast cancer. We developed a
      state-transition microsimulation model to examine the cost-effectiveness of three
      HBV screening strategies: (1) "No screening"; (2) "Screen-and-Treat to prevent
      reactivation" (screen-all) with either lamivudine/tenofovir (LAM/TDF) or
      entecavir (ETV); and (3) "Screen-and-Treat high-risk only" (screen-HR) and treat
      with either LAM/TDF or ETV. Model data were obtained from the published
      literature. We used a payer's perspective, a lifetime horizon, and a 5 % discount
      rate for the analysis. "Screen-all" would prevent at least 38 severe
      reactivations per 100,000 persons screened over the lifetime of the cohort.
      "Screen-all" was associated with an increase of 0.0034-0.0035 QALYs and an
      additional cost of C$164-C$266 per person, which translated into an incremental
      cost-effectiveness ratio of C$47,808/QALY-C$76,527/QALY gained compared with "No
      screening" depending on the antiviral therapy received. "Screen-all" was the most
      cost-effective strategy, while "Screen-HR" was inferior in all scenarios tested.
      HBV screening before adjuvant chemotherapy for breast cancer patients would
      prevent a significant number of reactivations, would likely be moderately cost
      effective, and may extend the lives of breast cancer patients. 

PMID- 25962694
TI  - Obesity as an independent risk factor for decreased survival in node-positive
      high-risk breast cancer.
AB  - Obese breast cancer patients have a higher risk of lymph node metastasis and a
      poorer prognosis compared to patients with normal weight. For obese women with
      node-positive breast cancer, an association between body weight and prognosis
      remains unclear. In this retrospective study, we analyzed patient data from the
      Phase-III ADEBAR trial, in which high-risk breast cancer patients (pT1-4, pN2-3,
      pM0) were randomized into a docetaxel-based versus epirubicin-based chemotherapy
      regimen. Patients were grouped according to their BMI value as underweight/normal
      weight (BMI < 25 kg/m(2); n = 543), overweight (BMI 25-29.9 kg/m(2); n = 482) or
      obese (BMI >= 30 kg/m(2); n = 285). Overweight and obese patients were older, had
      larger tumors and were more likely to be postmenopausal at the time of diagnosis
      compared to underweight/normal-weight patients (all p < 0.001). Multivariate Cox
      regression analyses adjusting for age and histopathological tumor features showed
      that obese patients had a significantly shorter disease-free survival (DFS; HR
      1.43; 95 % CI 1.11-1.86; p = 0.006) and overall survival (OS; HR 1.56; 95 % CI
      1.14-2.14; p = 0.006) than non-obese patients. Subgroup analyses revealed that
      the differences in DFS and OS were significant for postmenopausal but not for
      premenopausal patients, and that the survival benefit of non-obese patients was
      more pronounced in women with hormone-receptor-positive disease. Obesity
      constitutes an independent, adverse prognostic factor in high-risk node-positive
      breast cancer patients, in particular for postmenopausal women and women with
      hormone-receptor-positive disease. 

PMID- 25962693
TI  - AroER tri-screenTM is a novel functional assay to estimate both estrogenic and
      estrogen precursor activity of chemicals or biological specimens.
AB  - The purpose of the study is to define AroER tri-screen's utility for identifying
      endocrine-disrupting chemicals (EDCs) that target aromatase and/or estrogen
      receptor (ER), and to measure the total estrogenic activity in biological
      specimens. ER-positive, aromatase-expressing MCF-7 breast cancer cells were
      stably transfected with an estrogen responsive element (ERE)-driven luciferase
      reporter plasmid to yield a new high-throughput screening platform-the AroER tri
      screen. AroER tri-screen was capable of identifying estrogen precursors, such as
      cortodoxone, which function as estrogens through a two-step conversion process in
      aromatase-expressing tissue. Furthermore, the system proved useful for assessing
      EDC activity in biologically relevant samples. Estimating these activities is
      critical because natural estrogens and estrogenic EDCs are important factors in
      ER-positive breast cancer risk. As our research demonstrates, incorporating
      functionally active aromatase into the AroER tri-screen produces a powerful and
      unique tool to (1) identify new EDCs targeting aromatase and/or ER; (2) discover
      novel EDCs activated by aromatase; and (3) estimate overall estrogenic activities
      in biological samples as a potential intermediate risk factor for breast cancer.

PMID- 25962696
TI  - Fc-Gamma receptor polymorphism and gene expression of peripheral blood
      mononuclear cells in patients with HER2-positive metastatic breast cancer
      receiving single-agent trastuzumab.
AB  - AIM: The aim of this study was to investigate gene expression in the peripheral
      blood mononuclear cells (PBMCs) of patients with HER2-positive breast cancer
      receiving trastuzumab. We also evaluated the effect of Fc-gamma receptor genotype
      on trastuzumab-driven gene expression. MATERIALS AND METHODS: Gene expression was
      assessed by microarray analyses before and after administration of single-agent
      trastuzumab in 34 patients with metastatic HER2-positive breast cancer who were
      genotyped for Fc-gamma receptor (FcGR) IIA H131R and FcGRIIIA V158F. Gene set
      enrichment analysis (GSEA) was used to identify the gene sets that were
      significantly enriched after administration of trastuzumab in patient cohorts
      categorized by FcGR variant. RESULTS: At baseline three non-immune-related gene
      sets were identified only in patient cohort of FcGRIIA non-H/H variant. Thirty
      gene sets were identified in the cohort of FcGRIIIA V/V variants, while no gene
      set was identified in FcGRIIIA non-V/V variants one week after starting
      trastuzumab. Eleven gene sets were identified in FcGRIIA H/H variants 8 week
      after starting trastuzumab, but none in non-H/H variants. Immune-related gene
      sets were significantly down-regulated after administration of trastuzumab.
      CONCLUSION: The response of PBMCs to trastuzumab markedly varied with
      polymorphisms in FcGRIIA and FcGRIIIA. These results indicate that FcGR
      polymorphisms contribute to the systemic immune reaction triggered by
      trastuzumab. Further investigations are needed to clarify the biological effects
      of FcGR variation on the mechanism of trastuzumab activity.

PMID- 25962697
TI  - Evaluation of Surface Water Quality by Using GIS and a Heavy Metal Pollution
      Index (HPI) Model in a Coal Mining Area, India.
AB  - Twenty eight surface water samples were collected from fourteen sites of the West
      Bokaro coalfield, India. The concentration of Mn, Cu, Zn, Ni, As, Se, Al, Cr, Ba,
      and Fe were analyzed using inductively coupled plasma mass spectrometry (ICP-MS)
      for determination of seasonal fluctuations and a heavy metal pollution index
      (HPI). The HPI values were below the critical pollution index value of 100. Metal
      concentrations were higher in the pre-monsoon season as compared to the post
      monsoon season. The Zn, Ni, Mn, As, Se, Al, Ba, Cu, and Cr concentrations did not
      exceed the desirable limits for drinking water in either season. However, at many
      sites, concentrations of Fe were above the desirable limit of the WHO (2006) and
      Indian drinking water standard (BIS 2003) in both seasons. The water that
      contained higher concentrations of Fe would require treatment before domestic
      use.

PMID- 25962698
TI  - A stepwise assembly of a molecular box from 16-electron half-sandwich precursors
      [Cp*M(pdt)] (M = Rh, Ir).
AB  - The coordinatively-unsaturated 16-electron half-sandwich precursors [Cp*M(pdt)]
      (M = Rh, Ir; pdt = pyrazine-2,3-dithiol) have been synthesized. X-ray
      crystallography in combination with (1)H NMR analysis was used to elucidate the
      nature of the precursors. The Rh(iii) precursor displays a dimeric form in the
      trans arrangement in the solid state, formulated as [(Cp*Rh)2(MU(S)-pdt)2] (), in
      which covalent Rh-S bonds bridge the metal centers. In solution, however, dimers
      and monomers coexist in equilibrium. The dissociation equilibrium of in DMSO-d6
      was evaluated by (1)H NMR at several temperatures between 20 and 80  degrees C.
      The Ir(iii) precursor [Cp*Ir(pdt)] () is the monomeric form, and stable in the
      solid state and solution. Due to their unsaturation and bridging properties,
      these precursors were further used in stepwise assembly reactions with the
      binuclear building blocks to give open macrocycles and a closed molecular box. 

PMID- 25962695
TI  - The immunoregulatory and fibrotic roles of activin A in allergic asthma.
AB  - Activin A, a member of the TGF-beta superfamily of cytokines, was originally
      identified as an inducer of follicle stimulating hormone release, but has since
      been ascribed roles in normal physiological processes, as an immunoregulatory
      cytokine and as a driver of fibrosis. In the last 10-15 years, it has also become
      abundantly clear that activin A plays an important role in the regulation of
      asthmatic inflammation and airway remodelling. This review provides a brief
      introduction to the activin A/TGF-beta superfamily, focussing on the regulation
      of receptors and signalling pathways. We examine the contradictory evidence for
      generalized pro- vs. anti-inflammatory effects of activin A in inflammation,
      before appraising its role in asthmatic inflammation and airway remodelling
      specifically by evaluating data from both murine models and clinical studies. We
      identify key issues to be addressed, paving the way for safe exploitation of
      modulation of activin A function for treatment of allergic asthma and other
      inflammatory lung diseases.

PMID- 25962700
TI  - Fiber-Optic SPR Immunosensors Tailored To Target Epithelial Cells through
      Membrane Receptors.
AB  - We report, for the first time, the use of a surface plasmon resonance (SPR) fiber
      optic immunosensor for selective cellular detection through membrane protein
      targeting. The sensor architecture lies on gold-coated tilted fiber Bragg
      gratings (Au-coated TFBGs) photoimprinted in the fiber core via a laser
      technique. TFBGs operate in the near-infrared wavelength range at ~1550 nm,
      yielding optical and SPR sensing characteristics that are advantageous for the
      analyses of cellular bindings and technical compatibility with relatively low
      cost telecommunication-grade measurement devices. In this work, we take consider
      their numerous assets to figure out their ability to selectively detect intact
      epithelial cells as analytes in cell suspensions in the range of 2-5 * 10(6)
      cells mL(-1). For this, the probe was first thermally annealed to ensure a strong
      adhesion of the metallic coating to the fiber surface. Its surface was then
      functionalized with specific monoclonal antibodies via alkanethiol self-assembled
      monolayers (SAMs) against extracellular domain of epidermal growth factor
      receptors (EGFRs) and characterized by peak force tapping atomic force
      microscopy. A differential diagnosis has been demonstrated between two model
      systems. The developed immunosensors were able to monitor, in real time, the
      specific attachment of single intact cells in concentrations from 3 * 10(6) cells
      mL(-1). Such results confirm that the developed probe fits the lab-on-fiber
      technology and has the potential to be used as a disposable device for in situ
      and real-time clinical diagnosis. 

PMID- 25962699
TI  - Antipsychotic-induced weight gain in first-episode psychosis patients: a meta
      analysis of differential effects of antipsychotic medications.
AB  - AIM: The first-episode psychosis (FEP) represents a critical period to prevent
      cardiovascular and metabolic morbidity decades later. Antipsychotic (AP)-induced
      weight gain is one modifiable factor in this period. The purpose of this study is
      to conduct a meta-analysis of AP-induced weight and body mass index (BMI) change
      in FEP. METHODS: A comprehensive literature search identified 28 articles that
      reported data on AP-specific weight or BMI change in FEP. We conducted a meta
      analysis of short- and long-term mean weight and BMI differences between placebo
      and AP medications. We also performed subgroup and meta-regression analysis to
      examine weight, BMI outcomes and their relationship with location (Asian vs.
      Western), sponsorship and baseline weight and BMIs. RESULTS: Compared to placebo,
      AP-caused mean weight gain was 3.22 kg and 1.4 points BMI in the short-term, and
      5.30 kg and 1.86 points BMI in the long term. Clinically significant weight gain
      risk increased about twofold with AP use. Weight gain was associated with
      duration of AP use. AP medications were associated with more weight gain in
      Western samples as opposed to Asian samples. Most AP medications were associated
      with significant body weight gain and BMI increase in FEP patients, except for
      ziprasidone. Olanzapine and clozapine caused the highest weight gain compared to
      placebo. CONCLUSION: Except for ziprasidone, most AP medications were associated
      with body weight gain and BMI increase in FEP patients. Early and continuing
      effects of various AP medications on weight gain and BMI increase should be taken
      into consideration by clinicians.

PMID- 25962701
TI  - C1q/tumor necrosis factor-related protein-6 attenuates post-infarct cardiac
      fibrosis by targeting RhoA/MRTF-A pathway and inhibiting myofibroblast
      differentiation.
AB  - C1q/tumor necrosis factor-related protein-6 (CTRP6) is a newly identified
      adiponectin paralog with modulation effects on metabolism and inflammation.
      However, the cardiovascular function of CTRP6 remains unknown. This study aimed
      to determine its role in cardiac fibrosis and explore the possible mechanism.
      Myocardial infarction (MI) was induced by left anterior descending coronary
      artery ligation in rats. CTRP6 was mainly expressed in the cytoplasm of adult rat
      cardiomyocytes and significantly decreased in the border and infarct zones post
      MI. Adenovirus-mediated CTRP6 delivery improved cardiac function, attenuated
      cardiac hypertrophy, alleviated cardiac fibrosis, and inhibited myofibroblast
      differentiation as well as the expression of collagen I, collagen III, and
      connective tissue growth factor post-MI. In cultured adult rat cardiac
      fibroblasts (CFs), exogenous or cardiomyocyte-secreted CTRP6 inhibited, whereas
      knockdown of CTRP6 facilitated transforming growth factor-beta1 (TGF-beta1)
      induced expression of alpha-smooth muscle actin, smooth muscle 22alpha, and
      profibrotic molecules. CTRP6 had no effect on CFs proliferation but attenuated
      CFs migration induced by TGF-beta1. CTRP6 increased the phosphorylation of AMP
      activated protein kinase (AMPK) and Akt in CFs and post-MI hearts. Pretreatment
      with adenine 9-beta-D-arabinofuranoside (AraA), an AMPK inhibitor, or LY294002, a
      phosphatidylinositol-3-kinase (PI3 K) inhibitor, abolished the protective effect
      of CTRP6 on TGF-beta1-induced profibrotic response. Furthermore, CTRP6 had no
      effect on TGF-beta1-induced Smad3 phosphorylation and nuclear translocation,
      whereas significantly decreased TGF-beta1-induced RhoA activation and myocardin
      related transcription factor-A (MRTF-A) nuclear translocation, and these effects
      were blocked by AMPK or Akt inhibition. In conclusion, CTRP6 attenuates cardiac
      fibrosis via inhibiting myofibroblast differentiation. AMPK and Akt activation
      are responsible for the CTRP6-mediated anti-fibrotic effect by targeting
      RhoA/MRTF-A pathway. 

PMID- 25962702
TI  - SIRT3 deficiency impairs mitochondrial and contractile function in the heart.
AB  - Sirtuin 3 (SIRT3) is a mitochondrial NAD(+)-dependent deacetylase that regulates
      energy metabolic enzymes by reversible protein lysine acetylation in various
      extracardiac tissues. The role of SIRT3 in myocardial energetics and in the
      development of mitochondrial dysfunction in cardiac pathologies, such as the
      failing heart, remains to be elucidated. To investigate the role of SIRT3 in the
      regulation of myocardial energetics and function SIRT3(-/-) mice developed
      progressive age-related deterioration of cardiac function, as evidenced by a
      decrease in ejection fraction and an increase in enddiastolic volume at 24 but
      not 8 weeks of age using echocardiography. Four weeks following transverse aortic
      constriction, ejection fraction was further decreased in SIRT3(-/-) mice compared
      to WT mice, accompanied by a greater degree of cardiac hypertrophy and fibrosis.
      In isolated working hearts, a decrease in cardiac function in SIRT3(-/-) mice was
      accompanied by a decrease in palmitate oxidation, glucose oxidation, and oxygen
      consumption, whereas rates of glycolysis were increased. Respiratory capacity and
      ATP synthesis were decreased in cardiac mitochondria of SIRT3(-/-) mice. HPLC
      measurements revealed a decrease of the myocardial ATP/AMP ratio and of
      myocardial energy charge. Using LC-MS/MS, we identified increased acetylation of
      84 mitochondrial proteins, including 6 enzymes of fatty acid import and
      oxidation, 50 subunits of the electron transport chain, and 3 enzymes of the
      tricarboxylic acid cycle. Lack of SIRT3 impairs mitochondrial and contractile
      function in the heart, likely due to increased acetylation of various energy
      metabolic proteins and subsequent myocardial energy depletion. 

PMID- 25962703
TI  - Implementation and evaluation of a checklist to improve patient care on surgical
      ward rounds.
AB  - BACKGROUND: Key aspects of care may be overlooked on a busy surgical ward round.
      This study assessed the use of a checklist to correct these omissions. Its use as
      the basis of structured ward round documentation was then measured. METHODS:
      Using a structured checklist, key aspects of surgical care were observed and
      recorded during ward rounds. Initially, members of the surgical team were unaware
      of the checklist. Subsequently, rounds were performed with a designated member of
      the team acting as 'prompter' if aspects of care were not considered per the
      checklist. A structured ward round progress form was developed and its completion
      assessed before and after specific education in its use. Changes in the use of
      checklist and documentation using the structured form were analysed for
      statistical significance. RESULTS: Following the use of a checklist and prompting
      during ward rounds, significant improvement occurred in the consideration of the
      majority of criteria included in the checklist, all of which reached statistical
      significance (P < 0.05). Provision of a structured progress form did not
      initially improve documentation but this was substantially improved with specific
      education (P < 0.05). CONCLUSION: The use of a checklist during surgical ward
      rounds makes significant improvement in the consideration of most key aspects of
      care and education in the completion of a structured progress form substantially
      improved documentation.

PMID- 25962704
TI  - Corrigendum: Adiponectin receptor 1 conserves docosahexaenoic acid and promotes
      photoreceptor cell survival.

PMID- 25962705
TI  - Prenatal diagnosis of intra-abdominal cystic lesions by fetal ultrasonography:
      diagnostic agreement between prenatal and postnatal diagnosis.
AB  - OBJECTIVE: The aim of this study was to assess the diagnostic agreement between
      the prenatal diagnosis of intra-abdominal cystic lesions made by ultrasound
      examination and the postnatal diagnosis. METHODS: We reviewed all consecutive
      cases referred for an anechoic abdominal cyst from 2009 to 2013. Prenatal
      ultrasound diagnosis was compared with postnatal diagnosis. Prenatal diagnosis
      was defined as 'correct' if a specific prenatal diagnosis or one of the possible
      diagnoses was confirmed postnatally, as 'not confirmed' if the postnatal
      examination revealed no abnormalities and as 'incorrect' if the postnatal
      diagnosis was different from those suggested prenatally. RESULTS: Seventy-three
      cases were included, and prenatal diagnoses were made at a median gestational age
      of 27 weeks (range: 13-36). Correct diagnoses were made in 66 cases (90.4%),
      including four in which the lesion resolved spontaneously in utero; two diagnoses
      were 'not confirmed' postnatally, and one was incorrect (a prenatal diagnosis of
      intestinal duplication was in fact an anorectal malformation). Postnatal
      diagnosis was not achieved in four cases: None of them required surgery, and
      clinical follow-up was favorable. The abdominal cysts were isolated in 52 cases
      (71%) and associated with other anomalies in 21 cases (29%). Aneuploidies were
      diagnosed in three cases (all trisomy 21). Eight cases underwent termination of
      pregnancy; there were no fetal deaths and one neonatal death. Postnatal surgery
      was performed in 30 out of 65 liveborn infants (46.1%). CONCLUSION: Overall
      diagnostic agreement between prenatal and postnatal diagnosis of fetal intra
      abdominal cystic lesions is high.

PMID- 25962706
TI  - Are medical students skint on skin?

PMID- 25962707
TI  - Performance of HbA1c for the prediction of diabetes in a rural community in
      Korea.
AB  - AIM: To investigate the performance of HbA1c in predicting incident diabetes
      among Korean adults with normal fasting glucose and impaired fasting glucose
      levels. METHODS: This study used data from the Korean Genome Epidemiology Study
      Kangwha Study. A prospective analysis was carried out on 2079 people (820 men and
      1259 women) who completed follow-up examinations up until 2013. Diabetes was
      defined as fasting blood glucose level >= 7.0 mmol/l, HbA1c level >= 48 mmol/mol
      (6.5%), or current treatment for diabetes. Areas under the receiver-operating
      characteristic curves were used to assess the different performances of HbA1c ,
      glucose and insulin in predicting diabetes. RESULTS: The median follow-up time
      was 3.97 years, during which 7.7% of men and 6.3% of women developed incident
      diabetes. The areas under the receiver-operating curves (95% CI) for diabetes
      prediction were 0.740 (0.692-0.787) for HbA1c , 0.716 (0.667-0.764) for glucose
      and 0.598 (0.549-0.648) for insulin. HbA1c showed better predictive power in
      people with impaired fasting glucose (area under the curve 0.753, 95% CI 0.685
      0.821) than in those with normal glucose (area under the curve 0.648, 95% CI
      0.577-0.719). An HbA1c threshold of 40 mmol/mol (5.8%) was found to have the
      highest predictive value for diabetes, with a relative risk of 6.30 (95% CI 3.49
      11.35) in men and 3.52 (95% CI 2.06-6.03) in women after adjusting for age, waist
      circumference, triglycerides, hypertension, family history of diabetes, smoking,
      alcohol intake, exercise and baseline glucose level. CONCLUSIONS: HbA1c can be
      used to identify people at high risk for the development of diabetes, especially
      in those with impaired fasting glucose levels.

PMID- 25962708
TI  - Intrahepatic mass-forming cholangiocarcinoma: enhancement pattern on Gd-BOPTA-MRI
      with emphasis of hepatobiliary phase.
AB  - PURPOSE: To describe the Gd-BOPTA MRI findings of intrahepatic mass-forming type
      cholangiocarcinomas (IMCs), with emphasis on the hepatobiliary phase (HBP).
      METHODS: We reviewed retrospectively 29 IMC patients who underwent Gd-BOPTA-MRI
      between June, 2004 and June, 2014. Images were acquired prior to, and after,
      administration of 15-20 mL of Gd-BOPTA in the dynamic phase (arterial phase,
      portal venous phase, and 3-5 min phase), 10-15-min late phase, and 2-3 h HBP
      phase. RESULTS: In the dynamic phase, 27 (93%) lesions showed a peripheral rim
      like enhancement in the arterial and portal venous phases, followed by
      progressive filling-in on the delayed images. In 14 (56%) cases, a hypointense
      peripheral rim was identified in the 10-15-min late phase, delineating a target
      pattern. In the HBP, the cholangiocarcinoma showed a diffuse, mainly central and
      inhomogeneous enhancement (cloud of enhancement) in 28 (96%) patients; in 23
      (79%) cases, there was an association between cloud appearance and a hypointense
      peripheral rim, showing a target pattern. CONCLUSIONS: Gd-BOPTA MRI pattern of
      IMC on dynamic study is similar to that of conventional extracellular agents,
      that is peripheral enhancement with progressive and concentric filling of
      contrast material on delayed phases. At 10-15 min delayed phases, IMC shows often
      a peripheral hypointense rim consistent with a target appearance. In the HBP, due
      to progressive central enhancement (cloud) and peripheral hypointense rim, an
      higher number of tumors show a target appearance; this pattern is not specific
      and would also be expected to be seen in metastases from adenocarcinoma.

PMID- 25962710
TI  - The "staghorn" calculus.

PMID- 25962709
TI  - Sigmoid stenosis caused by diverticulitis vs. carcinoma: usefulness of
      sonographic features for their differentiation in the emergency setting.
AB  - OBJECTIVE: To retrospectively evaluate the accuracy of ultrasound as a diagnostic
      method for differentiating acute diverticulitis from colon cancer in patients
      with sigmoid colon stenosis. MATERIALS AND METHODS: Ultrasound examinations of 91
      consecutive patients with sigmoid stenosis (50 diverticulitis and 41 colon
      cancers) were reviewed by two trained radiologists. Sixty-five (71%) patients
      presented with acute abdominal symptoms. Thirteen sonographic criteria retrieved
      from the literature were evaluated to differentiate benign from malignant
      strictures. A score including all parameters which showed significant differences
      between benign vs. malignant was built. Sensitivity, specificity, accuracy, and
      positive or negative predictive values of each sonographic sign, the overall
      diagnosis, and sonographic score were calculated. RESULTS: Loss of the bowel wall
      stratification was the most reliable criteria for the diagnosis of malignancy
      (92% and 94% of sensitivity and specificity, respectively), and the best inter
      radiologist agreement (kappa = 0.848). Adjacent lymph nodes were the most
      specific feature (98%) for colon cancer, but its sensitivity was low. Global
      assessment could differentiate both diseases with high sensitivity (92-94.9%) and
      specificity (98-100%). Sonographic score >3 enabled differentiation of carcinoma
      from diverticulitis with 95% sensitivity and 92-94% specificity, with an area
      under the ROC curve of 0.98-0.987. There were no significant differences in the
      results between patients with acute and nonacute abdominal symptoms. CONCLUSION:
      The combination of several morphological sonographic findings using a score can
      differentiate most cases of diverticulitis from colon carcinoma in sigmoid
      strictures.

PMID- 25962713
TI  - Using a modified syringe technique to adjust the intracuff pressure of a
      laryngeal mask airway.
AB  - Limiting the intracuff pressure of a laryngeal mask airway (LMA) to <60 cmH2O is
      recommended in clinical practice. This report aimed to assess the efficacy of a
      modified syringe technique to adjust the intracuff pressure of an LMA. In a
      preclinical study, commercially available 20-mL syringes were attached to the
      pilot balloon of LMAs with different preset intracuff pressures (40 cmH2O, 50
      cmH2O, 60 cmH2O, 70 cmH2O, 80 cmH2O, 100 cmH2O, and 120 cmH2O). After attachment,
      the syringe plunger was allowed to passively rebound. If no rebound of the
      plunger was observed after attachment, 1 mL of air was withdrawn and the plunger
      was allowed to passively rebound again. This technique allowed the plunger to
      overcome static friction and avoid excessive deflation of the LMA cuffs. The
      intracuff pressure was measured using a manometer after the plunger ceased
      moving. In the preclinical study, the intracuff pressure was always less than or
      close to 60 cmH2O after adjustment using this modified syringe technique. After
      evaluating the performance and characteristics of the syringe in the preclinical
      study, we concluded that the modified syringe technique may be useful for
      adjusting LMA intracuff pressure effectively.

PMID- 25962712
TI  - Contemporary Trends of Optimal Evidence-Based Medical Therapy at Discharge for
      Patients Surviving Acute Myocardial Infarction From the Korea Acute Myocardial
      Infarction Registry.
AB  - BACKGROUND: Temporal trends of evidence-based optimal medical therapy (OMT) at
      discharge after acute myocardial infarction (AMI) have not been investigated in
      recent years. HYPOTHESIS: OMT should have been increased in AMI and gap between
      guidelines and practices in its use should have been narrowed. METHODS: We
      examined discharge medications of 17,578 post-MI patients who had no documented
      contraindications to antiplatelet agents, beta-blockers, angiotensin-converting
      enzyme inhibitors, or statins across a 6-year period (divided into subperiods of
      November 2005 to December 2006 [period 1], 2007 [period 2], 2008 [period 3], 2009
      [period 4], 2010 [period 5], and January to June 2011 [period 6]) in the Korean
      AMI Registry. OMT was defined as use of all 4 indicated medications. RESULTS:
      Marked increases in OMT (48.6% to 63.2%) were seen irrespective of age and sex,
      mainly attributed to marked increases in the use of beta-blockers (70.3% to
      83.7%) and statins (76.9% to 82.6%) from period 1 to period 6. The gap in use of
      OMT between men and women narrowed over time between the first and second 3
      periods, but not between the young and the elderly. Advanced age (odds ratio
      [OR]: 0.88, P = 0.04) was independently associated with underuse of OMT. Adjusted
      ORs for OMT from period 1 to period 6 were as follows: 1, 1.14 (P = 0.024), 1.21
      (P = 0.001), 1.40 (P < 0.001), 1.47 (P < 0.001), and 1.69 (P < 0.001),
      respectively. CONCLUSIONS: Despite gradual increase in OMT over time, the gap
      between guidelines and practices in use of OMT continues to exist.

PMID- 25962711
TI  - Corticotropin-releasing factor receptor type 1 and type 2 interaction in
      irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) displays chronic abdominal pain or discomfort with
      altered defecation, and stress-induced altered gut motility and visceral
      sensation play an important role in the pathophysiology. Corticotropin-releasing
      factor (CRF) is a main mediator of stress responses and mediates these
      gastrointestinal functional changes. CRF in brain and periphery acts through two
      subtype receptors such as CRF receptor type 1 (CRF1) and type 2 (CRF2), and
      activating CRF1 exclusively stimulates colonic motor function and induces
      visceral hypersensitivity. Meanwhile, several recent studies have demonstrated
      that CRF2 has a counter regulatory action against CRF1, which may imply that CRF2
      inhibits stress response induced by CRF1 in order to prevent it from going into
      an overdrive state. Colonic contractility and sensation may be explained by the
      state of the intensity of CRF1 signaling. CRF2 signaling may play a role in CRF1
      triggered enhanced colonic functions through modulation of CRF1 activity.
      Blocking CRF2 further enhances CRF-induced stimulation of colonic contractility
      and activating CRF2 inhibits stress-induced visceral sensitization. Therefore, we
      proposed the hypothesis, i.e., balance theory of CRF1 and CRF2 signaling as
      follows. Both CRF receptors may be activated simultaneously and the signaling
      balance of CRF1 and CRF2 may determine the functional changes of gastrointestinal
      tract induced by stress. CRF signaling balance might be abnormally shifted toward
      CRF1, leading to enhanced colonic motility and visceral sensitization in IBS.
      This theory may lead to understanding the pathophysiology and provide the novel
      therapeutic options targeting altered signaling balance of CRF1 and CRF2 in IBS. 

PMID- 25962714
TI  - The surface Laplacian technique in EEG: Theory and methods.
AB  - This paper reviews the method of surface Laplacian differentiation to study EEG.
      We focus on topics that are helpful for a clear understanding of the underlying
      concepts and its efficient implementation, which is especially important for EEG
      researchers unfamiliar with the technique. The popular methods of finite
      difference and splines are reviewed in detail. The former has the advantage of
      simplicity and low computational cost, but its estimates are prone to a variety
      of errors due to discretization. The latter eliminates all issues related to
      discretization and incorporates a regularization mechanism to reduce spatial
      noise, but at the cost of increasing mathematical and computational complexity.
      These and several other issues deserving further development are highlighted,
      some of which we address to the extent possible. Here we develop a set of
      discrete approximations for Laplacian estimates at peripheral electrodes. We also
      provide the mathematical details of finite difference approximations that are
      missing in the literature, and discuss the problem of computational performance,
      which is particularly important in the context of EEG splines where data sets can
      be very large. Along this line, the matrix representation of the surface
      Laplacian operator is carefully discussed and some figures are given illustrating
      the advantages of this approach. In the final remarks, we briefly sketch a
      possible way to incorporate finite-size electrodes into Laplacian estimates that
      could guide further developments. 

PMID- 25962715
TI  - Periodontal Specific Differentiation of Dental Follicle Stem Cells into
      Osteoblast, Fibroblast, and Cementoblast.
AB  - The dental follicle is a source of dental follicle stem cells (DFCs), which have
      the potential to differentiate into the periodontal lineage. DFCs therefore are
      of value in dental tissue engineering. The purpose of this study was to evaluate
      the effect of growth factor type and concentration on DFC differentiation into
      periodontal specific lineages. DFCs were isolated from the human dental follicle
      and characterized for the expression of mesenchymal markers. The cells were
      positive for CD-73, CD-44, and CD-90; and negative for CD-33, CD-34, and CD-45.
      The expression of CD-29 and CD-31 was almost negligible. The cells also expressed
      periodontal ligament and cementum markers such as periodontal ligament-associated
      protein-1 (PLAP-1), fibroblast growth factor-2 (FGF-2), and cementum protein-1
      (CEMP-1), however, the expression of osteoblast markers was absent. Further, the
      DFCs were cultured in three different induction medium to analyze the
      osteoblastic, fibroblastic, and cementoblastic differentiation. Runt-related
      transcription factor 2 (RUNX-2), alkaline phosphatase (ALP) activity, alizarin
      staining, calcium quantification, collagen type-1 (Col-1), and osteopontin (OPN)
      expression confirmed the osteoblastic differentiation of DFCs. DFCs cultured in
      recombinant human FGF-2 (rhFGF-2) containing medium showed enhanced PLAP-1, FGF
      2, and COL-1 expression with increasing concentration of rhFGF-2 which thereby
      confirmed periodontal ligament fibroblastic differentiation. Similarly, DFCs
      cultured in recombinant human cementum protein-1 (rhCEMP-1) containing medium
      showed enhanced bone sialoprotein-2 (BSP-2), CEMP-1, and COL-1 expression with
      respect to rhCEMP-1 which confirmed cementoblastic differentiation. The
      expression of osteoblast, fibroblast, and cementoblast-related genes of DFCs
      cultured in induction medium was enhanced in comparison to DFCs cultured in
      noninduction medium. Thus, growth factor-dependent differentiation of DFCs into
      periodontal specific lineages was proved by quantitative analysis. 

PMID- 25962716
TI  - Protein carbonyl levels correlate with performance in elite field hockey players.
AB  - Excess and incorrectly selected exercise can degrade athletic performance from an
      imbalance in redox homeostasis and oxidative stress, but well-planned training
      and nutrition can improve antioxidant capacity. The aim of the study was to
      investigate how nutrient intake could influence oxidative stress and cell lesion
      biomarkers after 5 days of training followed by a game. Blood was collected from
      10 athletes at the start of training (basal), after training (pre-game), and
      postgame. Their acceleration capacity also was measured pre- and postgame. Blood
      analysis showed an increase in lactate concentration postgame (13%) and total
      antioxidant capacity increased both pre-game (13.1%) and postgame (12.7%), all in
      comparison with basal levels. An oxidative stress marker, protein carbonyl (PC),
      increased 3-fold over the course of the game, which correlated with a decreased
      acceleration (r = 0.749). For biomarkers of tissue damage, creatine kinase and
      aspartate transaminase (AST) increased postgame by 150% and 75%, respectively.
      The AST variation had a high negative correlation with energy and carbohydrate
      consumption and a moderate correlation with lipid and vitamin C intake. Protein
      intake had a positive but moderate correlation with reduced glutathione. The
      observed correlations suggest that nutritional monitoring can improve exercise
      physiological homeostasis and that PC serves as a good biomarker for oxidative
      stress and performance loss. 

PMID- 25962717
TI  - Safety and Activity of the First-in-Class Sym004 Anti-EGFR Antibody Mixture in
      Patients with Refractory Colorectal Cancer.
AB  - Tumor growth in the context of EGFR inhibitor resistance may remain EGFR
      dependent and is mediated by mechanisms including compensatory ligand
      upregulation and de novo gene alterations. Sym004 is a two-antibody mixture
      targeting nonoverlapping EGFR epitopes. In preclinical models, Sym004 causes
      significant EGFR internalization and degradation, which translates into superior
      growth inhibition in the presence of ligands. In this phase I trial, we observed
      grade 3 skin toxicity and hypomagnesemia as mechanism-based dose-limiting events
      during dose escalation. In dose-expansion cohorts of 9 and 12 mg/kg of Sym004
      weekly, patients with metastatic colorectal cancer and acquired EGFR inhibitor
      resistance were enrolled; 17 of 39 patients (44%) had tumor shrinkage, with 5
      patients (13%) achieving partial response. Pharmacodynamic studies confirmed
      marked Sym004-induced EGFR downmodulation. MET gene amplification emerged in 1
      patient during Sym004 treatment, and a partial response was seen in a patient
      with EGFR(S492R) mutation that is predictive of cetuximab resistance.
      SIGNIFICANCE: Potent EGFR downmodulation with Sym004 in patients with metastatic
      colorectal cancer and acquired resistance to cetuximab/panitumumab translates
      into significant antitumor activity and validates the preclinical hypothesis that
      a proportion of tumors remains dependent on EGFR signaling. Further clinical
      development and expanded correlative analyses of response patterns with secondary
      RAS/EGFR mutations are warranted.

PMID- 25962718
TI  - Cochlear Implantation, Enhancements, Transhumanism and Posthumanism: Some Human
      Questions.
AB  - Biomedical engineering technologies such as brain-machine interfaces and
      neuroprosthetics are advancements which assist human beings in varied ways. There
      are exciting yet speculative visions of how the neurosciences and bioengineering
      may influence human nature. However, these could be preparing a possible pathway
      towards an enhanced and even posthuman future. This article seeks to investigate
      several ethical themes and wider questions of enhancement, transhumanism and
      posthumanism. Four themes of interest are: autonomy, identity, futures, and
      community. Three larger questions can be asked: will everyone be enhanced? Will
      we be "human" if we are not, one day, transhuman? Should we be enhanced or not?
      The article proceeds by concentrating on a widespread and sometimes controversial
      application: the cochlear implant, an auditory prosthesis implanted into Deaf
      patients. Cochlear implantation and its reception in both the deaf and hearing
      communities have a distinctive moral discourse, which can offer surprising
      insights. The paper begins with several points about the enhancement of human
      beings, transhumanism's reach beyond the human, and posthuman aspirations. Next
      it focuses on cochlear implants on two sides. Firstly, a shorter consideration of
      what technologies may do to humans in a transhumanist world. Secondly, a deeper
      analysis of cochlear implantation's unique socio-political movement, its ethical
      explanations and cultural experiences linked with pediatric cochlear implantation
      and how those wary of being thrust towards posthumanism could marshal such ideas
      by analogy. As transhumanism approaches, the issues and questions merit
      continuing intense analysis. 

PMID- 25962719
TI  - Making Choices: Ethical Decisions in a Global Context.
AB  - The changing milieu of research--increasingly global, interdisciplinary and
      collaborative--prompts greater emphasis on cultural context and upon partnership
      with international scholars and diverse community groups. Ethics training,
      however, tends to ignore the cross-cultural challenges of making ethical choices.
      This paper confronts those challenges by presenting a new curricular model
      developed by an international team. It examines ethics across a very broad range
      of situations, using case studies and employing the perspectives of social
      science, humanities and the sciences. The course has been developed and taught in
      a highly collaborative way, involving researchers and students at Zhejiang
      University, the Indian Institute of Technology, Bombay and Brown University. The
      article presents the curricular modules of the course, learning outcomes, an
      assessment framework developed for the project, and a discussion of evaluation
      findings.

PMID- 25962720
TI  - High prevalence of discordant human papillomavirus and p16 oropharyngeal squamous
      cell carcinomas in an African American cohort.
AB  - BACKGROUND: Most studies on human papillomavirus (HPV)-associated oropharyngeal
      squamous cell carcinoma (SCC) have been performed on white Americans. Our study
      examined the incidence of HPV in an African American oropharyngeal SCC cohort and
      its survival. METHODS: African American patients with oropharyngeal SCC in a
      combined tumor registry were identified. HPV16 testing was performed by
      polymerase chain reaction (PCR) from DNA extracted from tumor blocks. The p16
      staining was performed using standard immunohistochemistry. RESULTS: Forty-four
      patients were identified for analysis. Seventy-three percent of the tumors were
      HPV-positive. Only 39% of the patients who were HPV-positive were also p16
      positive. Survival between all 3 tumor types, patients who tested HPV
      positive/p16, HPV-positive/p16-positive, and HPV-negative/p16-negative was
      significantly different (p = .03). HPV/p16 status was significant on univariate
      and multivariate analysis. CONCLUSION: HPV oropharyngeal SCC is strongly present
      in this African American cohort. Two thirds of the patients who were HPV-positive
      were p16-negative. Greater study is needed to explain the high p16 negativity
      among this HPV-positive oropharyngeal SCC African American cohort. (c) 2015 Wiley
      Periodicals, Inc. Head Neck 38: E867-E872, 2016.

PMID- 25962721
TI  - Red meat, processed meat and the risk of venous thromboembolism: friend or foe?
AB  - Venous thromboembolism (VTE) is a highly prevalent condition worldwide, which can
      be triggered by a combination of inherited and acquired risk factors, including
      diet. Several lines of evidence suggest that consumption of red and processed
      meat is associated with a significant risk of colorectal cancer, cardiovascular
      disease and diabetes. Therefore, an electronic search was conducted to identify
      clinical studies investigating the potential association between the risk of
      venous thrombosis and consumption of red or processed meat. Seven articles were
      finally included in this review, 6 prospective studies and 1 case-control
      investigation. Taken together, the evidence of the current scientific literature
      suggests that whether or not a pathophysiological link may exist between red or
      processed meat consumption and venous thrombosis, the association is definitely
      weak, since it was found to be non-statistically significant in four prospective
      cohort studies, marginally significant in one prospective cohort study and highly
      significant in the remaining prospective cohort study. In the single case-control
      study, the risk was also found to be non-statistically significant. Although
      further studies will be needed to definitely establish the existence of a
      thrombotic risk associated with different subtypes of red or processed meat, it
      seems premature to conclude that a reduced consumption of red and processed meat
      lowers the risk of VTE. 

PMID- 25962722
TI  - Mass spectrometric and charge density studies of organometallic clusters
      photoionized by gigawatt laser pulses.
AB  - Clusters on exposure to nanosecond laser pulses of gigawatt intensity exhibit a
      variety of photo-chemical processes such as fragmentation, intracluster reaction,
      ionization, Coulomb explosion, etc. Present article summarizes the experimental
      results obtained in our laboratory utilizing time-of-flight mass spectrometer
      which deal with one such aspect of cluster photochemistry related to generation
      of multiply charged atomic ions upon excessive ionization of cluster constituents
      (Coulomb explosion) at low intensity laser field (~109  W/cm2 ). To understand
      the mechanism of laser-cluster interaction, laser as well as cluster parameters
      were varied. Mass spectrometric studies were carried out at different laser
      wavelength as well as varying the nature of cluster constituents, backup
      pressure, nozzle diameter, etc. In addition, charge density measurements were
      also preformed to get information about the total number of ions generated upon
      laser-cluster interaction as a function of laser wavelength. In case of pure
      molecular clusters, the charge state of atomic ions as well as charge density was
      observed to enhance with increasing laser wavelength, signifying efficient
      coupling of the cluster medium with nanosecond laser pulse at longer wavelength.
      While in case of clusters doped with species having comparatively lower
      ionization energy, the efficiency of laser-cluster interaction was less, in
      contrast to studies carried out using femtosecond lasers. Results obtained in the
      present work have been rationalized on the basis of proposed three-stage cluster
      ionization mechanism, that is, multiphoton ionization ignited-inverse
      Bremsstrahlung heating and electron ionization. (c) 2015 Wiley Periodicals, Inc.
      Mass Spec Rev. 36:188-212, 2017.

PMID- 25962723
TI  - Sixty-Year-Old Man With Acute Epigastric Pain and Increased Serum Lipase Level.

PMID- 25962724
TI  - Erratum to: Change in Oral Impacts on Daily Performances (OIDP) with increasing
      age: testing the evaluative properties of the OIDP frequency inventory using
      prospective data from Norway and Sweden.

PMID- 25962725
TI  - The impact of demographic and perceptual variables on a young adult's decision to
      be covered by private health insurance.
AB  - BACKGROUND: The large number of uninsured individuals in the United States
      creates negative consequences for those who are uninsured and for those who are
      covered by health insurance plans. Young adults between the ages of 18 and 24 are
      the largest uninsured population subgroup. This subgroup warrants analysis. The
      major aim of this study is to determine why young adults between the ages of 18
      and 24 are the largest uninsured population subgroup. METHODS: The present study
      seeks to determine why young adults between the ages of 18 and 24 are the largest
      population subgroup that is not covered by private health insurance. Data on
      perceived health status, perceived need, perceived value, socioeconomic status,
      gender, and race was obtained from a national sample of 1,340 young adults from
      the 2005 Medical Expenditure Panel Survey and examined for possible explanatory
      variables, as well as data on the same variables from a national sample of 1,463
      from the 2008 Medical Expenditure Panel Survey. RESULTS: Results of the
      structural equation model analysis indicate that insurance coverage in the 2005
      sample was largely a function of higher socioeconomic status and being a non
      minority. Perceived health status, perceived need, perceived value, and gender
      were not significant predictors of private health insurance coverage in the 2005
      sample. However, in the 2008 sample, these indicators changed. Socioeconomic
      status, minority status, perceived health, perceived need, and perceived value
      were significant predictors of private health insurance coverage. CONCLUSIONS:
      The results of this study show that coverage by a private health insurance plan
      in the 2005 sample was largely a matter of having a higher socioeconomic status
      and having a non-minority status. In 2008 each of the attitudinal variables
      (perceived health, perceived value, and perceived need) predicted whether
      subjects carried private insurance. Our findings suggest that among those
      sampled, the young adult subgroup between the ages of 18 and 24 does not
      necessarily represent a unique segment of the population, with behaviors
      differing from the rest of the sample.

PMID- 25962726
TI  - Targeting epidermal fatty acid binding protein for treatment of experimental
      autoimmune encephalomyelitis.
AB  - BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease in which
      dysregulated immune cells attack myelin in the central nervous system (CNS),
      leading to irreversible neuronal degeneration. Our previous studies have
      demonstrated that epidermal fatty acid binding protein (E-FABP), widely expressed
      in immune cells, in particular in dendritic cells (DCs) and T lymphocytes, fuels
      the overactive immune responses in the mouse model of experimental autoimmune
      encephalomyelitis (EAE). METHODS: In the present study, we conducted an intensive
      computational docking analysis to identify novel E-FABP inhibitors for regulation
      of immune cell functions and for treatment of EAE. RESULTS: We demonstrate that
      compound [2-(4-acetylphenoxy)-9,10-dimethoxy-6,7-dihydropyrimido[6,1
      a]isoquinolin-4-one; designated as EI-03] bound to the lipid binding pocket of E
      FABP and enhanced the expression of peroxisome proliferator-activating receptor
      (PPAR) gamma. Further in vitro experiments showed that EI-03 regulated DC
      functions by inhibition of TNFalpha production while promoting IL-10 secretion.
      Moreover, EI-03 treatment counterregulated T cell balance by decreasing effector
      T cell differentiation (e.g. Th17, Th1) while increasing regulatory T cell
      development. Most importantly, mice treated with this newly identified compound
      exhibited reduced clinical symptoms of EAE in mouse models. CONCLUSIONS: Taken
      together, we have identified a new compound which displays a potential
      therapeutic benefit for treatment of MS by targeting E-FABP.

PMID- 25962727
TI  - Transcriptomic analysis of wheat near-isogenic lines identifies PM19-A1 and A2 as
      candidates for a major dormancy QTL.
AB  - BACKGROUND: Next-generation sequencing technologies provide new opportunities to
      identify the genetic components responsible for trait variation. However, in
      species with large polyploid genomes, such as bread wheat, the ability to rapidly
      identify genes underlying quantitative trait loci (QTL) remains non-trivial. To
      overcome this, we introduce a novel pipeline that analyses, by RNA-sequencing,
      multiple near-isogenic lines segregating for a targeted QTL. RESULTS: We use this
      approach to characterize a major and widely utilized seed dormancy QTL located on
      chromosome 4AL. It exploits the power and mapping resolution afforded by large
      multi-parent mapping populations, whilst reducing complexity by using multi
      allelic contrasts at the targeted QTL region. Our approach identifies two
      adjacent candidate genes within the QTL region belonging to the ABA-induced Wheat
      Plasma Membrane 19 family. One of them, PM19-A1, is highly expressed during grain
      maturation in dormant genotypes. The second, PM19-A2, shows changes in sequence
      causing several amino acid alterations between dormant and non-dormant genotypes.
      We confirm that PM19 genes are positive regulators of seed dormancy. CONCLUSIONS:
      The efficient identification of these strong candidates demonstrates the utility
      of our transcriptomic pipeline for rapid QTL to gene mapping. By using this
      approach we are able to provide a comprehensive genetic analysis of the major
      source of grain dormancy in wheat. Further analysis across a diverse panel of
      bread and durum wheats indicates that this important dormancy QTL predates
      hexaploid wheat. The use of these genes by wheat breeders could assist in the
      elimination of pre-harvest sprouting in wheat.

PMID- 25962728
TI  - Sex differences in the impact of the Mediterranean diet on systemic inflammation.
AB  - BACKGROUND: Some intervention trials have reported a reduction in systemic
      inflammation with the Mediterranean diet (MedDiet) while others have observed no
      effect. Despite the fact that sex differences have been highlighted in the
      inflammatory regulation, it is still not known whether MedDiet exerts similar
      effects on systemic inflammation in men and women. The aim of this study was
      therefore to investigate sex differences in the effects of the MedDiet on high
      sensitivity C-reactive protein (hs-CRP). FINDINGS: Participants were 35 men and
      27 premenopausal women (24-53 years) presenting a slightly deteriorated lipid
      profile. All foods were provided to participants during a 4-week isocaloric
      MedDiet. At baseline, women had higher hs-CRP concentrations than men (P = 0.03).
      No sex difference was observed in hs-CRP response to the MedDiet (P for sex-by
      time interaction = 0.36), with both men and women experiencing no change
      (respectively P = 0.62 and P > 0.99). When subgroups were formed according to hs
      CRP concentration before the MedDiet phase, men with elevated baseline values
      (>=2 mg/l) experienced a reduction in hs-CRP over time with the MedDiet (-26.5 %)
      while an increase was observed in men with lower baseline values (+96.6 %; P for
      group-by-time interaction = 0.02). This pattern of change was not observed in
      women. CONCLUSIONS: Results from this controlled feeding study suggest that men
      and women have similar effects from the MedDiet on systemic inflammation. The
      individual's overall inflammatory status seems to influence these effects, but
      only in men. TRIAL REGISTRATION: This clinical trial was registered at
      www.clinicaltrials.gov as NCT01293344 .

PMID- 25962729
TI  - Costs of dengue in three French territories of the Americas: an analysis of the
      hospital medical information system (PMSI) database.
AB  - BACKGROUND: Dengue is a major emerging public health concern in tropical and
      subtropical countries. Severe dengue can lead to hospitalisation and death. This
      study was performed to assess the economic burden of hospitalisations for dengue
      from 2007 to 2011 in three French territories of the Americas where dengue is
      endemic (French Guiana, Martinique and Guadeloupe). METHODS: Data on dengue
      associated hospitalisations were extracted from the French national hospital
      administrative database, Programme de Medicalisation des Systemes d'Information
      (PMSI). The numbers of stays and the corresponding number of hospitalised
      patients were determined using disease-specific ICD-10 codes. Associated hospital
      costs were estimated from the payer perspective, using French official tariffs.
      RESULTS: Overall, 4183 patients (mean age 32 years; 51 % male) were hospitalised
      for dengue, corresponding to 4574 hospital stays. In nearly all hospital stays
      (98 %; 4471), the illness was medically managed and the mean length of stay was
      4.3 days. The mean cost per stay was ?2522, corresponding to a total hospital
      cost of ?11.5 million over the 5 years assessed. The majority of hospitalisations
      (80 % of patients) and associated costs (75 % of total hospital costs) were
      incurred during two epidemics. CONCLUSION: Severe dengue is associated with
      significant hospital costs that escalate during outbreaks.

PMID- 25962730
TI  - Peri-pubertal administration of 3-nitro-1,2,4-triazol-5-one (NTO) affects
      reproductive organ development in male but not female Sprague Dawley rats.
AB  - Nitrotriazolone (3-nitro-1,2,4-triazol-5-one; NTO) is an insensitive munition
      that has demonstrated effects on reproductive organs in adult male rats. NTO was
      administered to male (0, 250, and 500milligrams per kilogram per day (mg/kg-day))
      and female (0, 500, and 1000mg/kg-day) Sprague-Dawley rats (15/sex/group) via
      oral gavage from weaning through post-natal day 53/54 and 42/43, respectively.
      Age and body mass at vaginal opening (VO) and preputial separation (PPS), as well
      as all measures of estrous cyclicity were not affected by treatment with NTO.
      Males treated with NTO exhibited reductions in testis mass associated with
      tubular degeneration/atrophy. Less pronounced reductions in accessory sex organ
      masses were also observed in the 500mg/kg-day group. Treatment with NTO did not
      affect thyroid hormone or testosterone levels. These findings suggest that NTO is
      not acting as an estrogen or thyroid active compound, but may indicate effects on
      steroidogenesis and/or direct testicular toxicity. 

PMID- 25962731
TI  - Comparative analysis of goitrogenic effects of phenylthiourea and methimazole in
      zebrafish embryos.
AB  - Craniofacial malformations, reduced locomotion and induction of genes encoding
      for enzymes involved in thyroid hormone synthesis were assessed using methimazole
      and N-phenylthiourea in zebrafish embryos. Gene expression, the most sensitive
      endpoint (EC50_MMI=372-765MUM, EC50_PTU=7.6-8.6MUM), was analysed in wild-type
      and in a transgenic strain, tg(tg:mCherry), expressing mCherry fluorescence
      protein under the control of the thyroglobulin gene. Reduction of locomotion and
      craniofacial malformations were observed at one or two orders of magnitude above
      concentrations affecting gene expression, respectively. Both effects could be
      linked to the malformations caused by reduced thyroxin levels. Our results show
      that due to the presence of the autoregulatory loop of the hypothalamus-pituitary
      thyroid axis, various molecular initiating events of thyroid disruption are
      amenable for the zebrafish embryo. We propose the tg(tg:mCherry) bioassay as a
      sensitive tool in medium scale screening of goitrogens, given the minimal effort
      for sample preparation and analysis of gene expression. 

PMID- 25962732
TI  - Analysis of 17 cases of posterior vertebral column resection in treating
      thoracolumbar spinal tuberculous angular kyphosis.
AB  - OBJECTIVE: This study aims to explore the efficacy and safety of posterior
      vertebral column resection (PVCR) in treating thoracolumbar spinal tuberculous
      angular kyphosis (TSTAK). METHODS: From January 2008 to January 2012, 17 TSTAK
      patients were treated surgically, including five males and 12 females, with an
      average age of 23.6 years, among five cases who had the kyphotic apical vertebrae
      located at the thoracic vertebrae, ten cases were located at the thoracolumbar
      segment, and two cases were located at the lumbar vertebrae. The kyphotic Cobb
      angle was measured in the preoperative, postoperative, and final follow-up,
      respectively, and the nerve function ASIA classification was assessed. RESULTS:
      The mean operative time was 364 min; the average intraoperative blood loss was
      2,218 ml; and the average intraoperative blood transfusion was 1,863 ml. Among
      the five patients with the preoperative nerve function as grade D, four of them
      recovered to grade E. The preoperative average Cobb angle was 81.3 degrees  +/-
      12.8 degrees , while the postoperative average Cobb average was 17.3 degrees  +/-
      3.6 degrees ; while it was significantly improved than the preoperative (P <
      0.01), the average kyphosis correction rate was 68.7% +/- 6.5%; the postoperative
      average follow-up was 18.7 months, with an average correction loss as 3.3 degrees
      . CONCLUSION: PVCR could be safely and effectively used in TSTAK.

PMID- 25962733
TI  - Producing the 'problem of drugs': A cross national-comparison of 'recovery'
      discourse in two Australian and British reports.
AB  - The notion of 'recovery' as an overarching approach to drug policy remains
      controversial. This cross-national analysis considers how the problem of drugs
      was constructed and represented in two key reports on the place of 'recovery' in
      drug policy, critically examining how the problem of drugs (and the people who
      use them) are constituted in recovery discourse, and how these problematisations
      are shaped and disseminated. Bacchi's poststructuralist approach is applied to
      two documents (one in Britain and one in Australia) to analyse how the 'problem
      of drugs' and the people who use them are constituted: as problematic users,
      constraining alternative understandings of the shifting nature of drug use; as
      responsibilised individuals (in Britain) and as patients (in Australia); as
      worthy of citizenship in the context of treatment and recovery, silencing the
      assumption of unworthiness and the loss of rights for those who continue to use
      drugs in 'problematic' ways. The position of the organisations which produced the
      reports is considered, with the authority of both organisations resting on their
      status as independent, apolitical bodies providing 'evidence-based' advice. There
      is a need to carefully weigh up the desirable and undesirable political effects
      of these constructions. The meaning of 'recovery' and how it could be realised in
      policy and practice is still being negotiated. By comparatively analysing how the
      problem of drugs was produced in 'recovery' discourse in two jurisdictions, at
      two specific points in the policy debate, we are reminded that ways of thinking
      about 'problems' reflect specific contexts, and how we are invoked to think about
      policy responses will be dependent upon these conditions. As 'recovery' continues
      to evolve, opening up spaces to discuss its contested meanings and effects will
      be an ongoing endeavour. 

PMID- 25962734
TI  - Plasma oligomeric alpha-synuclein is associated with glucocerebrosidase activity
      in Gaucher disease.
AB  - BACKGROUND: The link between Parkinson's disease (PD) and Gaucher disease (GD),
      the most common lysosomal storage disease associated with loss of
      glucocerebrosidase (GBA) activity, can be explained by abnormal accumulation of
      oligomeric alpha-synuclein (alpha-Syn) species resulting from mutations in the
      GBA gene. However, in GD, the relationship between GBA activity and alpha-Syn
      accumulation in biological fluids has not been investigated. METHODS: We analyzed
      plasma oligomeric alpha-Syn levels, leucocyte GBA activity, and plasma
      chitotriosidase activity in 21 patients with GD. RESULTS: Negative correlation
      between plasma oligomeric alpha-Syn levels, and leucocyte GBA activity was
      observed in patients with GD (R(2)  = 0.487; P < 0.001). CONCLUSION: The decrease
      in GBA activity may influence alpha-Syn oligomerization, explaining the high risk
      of PD development in GD patients. (c) 2015 International Parkinson and Movement
      Disorder Society.

PMID- 25962735
TI  - Ginkgo biloba extract enhances chemotherapy sensitivity and reverses
      chemoresistance through suppression of the KSR1-mediated ERK1/2 pathway in
      gastric cancer cells.
AB  - Kinase suppressor of Ras 1 (KSR1) is a scaffold protein that modulates the
      activation of the oncogenic mitogen-activated protein kinase (MAPK)/extracellular
      signal-regulated kinase (ERK) signaling pathway. Ginkgo biloba extract (EGb) 761
      has been demonstrated to possess antitumor activity that may be related to the
      KSR1-mediated ERK signaling pathway. However, the roles and its underlying
      mechanism in gastric cancer are unclear. In the present study, 62 gastric cancer
      and matched normal tissues were exploited for immunohistochemistry and real-time
      fluorescent quantitative PCR detection. Results of the immunohistochemistry
      showed that the expression of ERK1/2 and p-ERK1/2 was correlated to the
      expression of KSR1 and p-KSR1 in the gastric cancer tissues, and the
      overexpression of KSR1, p-KSR1, ERK1/2 and p-ERK1/2 was significantly associated
      with histological grade, TNM stage, lymph node and distant metastasis. Compared
      with the normal tissues, the relative mRNA copy values of KSR1, ERK1 and ERK2 in
      the cancer tissues were 2.43 +/- 0.49, 2.10 +/- 0.44 and 3.65 +/- 0.94. In
      addition, the expression of KSR1, p-KSR1, ERK1/2 and p-ERK1/2 in human gastric
      cancer multidrug resistant SGC-7901/CDDP cells was higher than that in the SGC
      7901 cells as detected by the methods of immunocytochemistry and western blot
      analysis. EGb 761 not only suppressed expression of these proteins induced by
      cisplatin (CDDP) and etoposide in SGC-7901 cells, but also inhibited expression
      of these proteins in the SGC-7901/CDDP cells. Meanwhile, the proliferation
      suppressing and apoptosis-inducing capacities of CDDP and etoposide were enhanced
      following combined treatment with EGb 761. Moreover, EGb 761 reduced the
      malondialdehyde (MDA) content and elevated the activities of superoxide dismutase
      (SOD) and glutathione peroxidase (GSH-Px) in the tumor cells. These results
      confirmed that activation of the KSR1-mediated ERK1/2 signaling pathway may
      contribute to tumorigenesis, metastasis and chemoresistance of human gastric
      cancer. EGb 761 enhanced the chemotherapy sensitivity and reversed the
      chemoresistance through suppression of the KSR1-mediated ERK1/2 pathway in
      gastric cancer cells, and the underlying mechanism may be related to its
      antioxidative activity.

PMID- 25962737
TI  - Hypertrophic adenoids in patients with nasopharyngeal carcinoma: appearance at
      magnetic resonance imaging before and after treatment.
AB  - INTRODUCTION: Patients with nasopharyngeal carcinoma (NPC) sporadically develop
      abnormal adenoids. Nasopharyngeal adenoids are usually included in the gross
      tumor volume (GTV) but may have different therapeutic responses than tumor
      tissue. Therefore, distinguishing adenoids from tumor tissue may be required for
      precise and efficient chemoradiotherapy and radiotherapy. We characterized
      nasopharyngeal adenoids and investigated the therapeutic responses of NPC and
      nasopharyngeal adenoids using magnetic resonance imaging (MRI). METHODS: MRI data
      from 40 NPC patients with a coexisting adenoid mass before and after treatment
      were analyzed. The features of the adenoid masses, including location, striped
      appearance, size, interface, symmetry/asymmetry, and cysts, were evaluated.
      Treatment response were scored according to the World Health Organization
      guidelines. RESULTS: A striped appearance was observed in 36 cases before
      treatment and in all cases after treatment. In these 36 cases, the average GTVs
      including and excluding the uninvolved adenoids were 19.8 cm3 and 14.8 cm3,
      respectively. The average percentage change after excluding the uninvolved
      adenoids from the GTV was 31.0%. Stable disease in the adenoids was identified in
      27 (96.4%) of 28 patients after neoadjuvant chemotherapy, while NPC clearly
      regressed. Partial adenoid responses were identified in 33 (82.5%) of 40 patients
      at 3 months after chemoradiotherapy or radiotherapy, whereas complete tumor
      responses were achieved in all patients. Six months after treatment, the adenoids
      continued to atrophy but did not disappear, and tumor recurrence was not found.
      CONCLUSIONS: Nasopharyngeal adenoids and carcinoma tissue in NPC patients can be
      distinguished by using MRI and have different responses to chemoradiotherapy and
      radiotherapy. These findings contribute to better delineating the GTV of NPC,
      based on which spatially optimized strategies can be developed to render precise
      and efficient chemoradiotherapy and radiotherapy. Additionally, we observed a
      clear difference in the responses of these two tissue types to current therapies.
      This finding may reduce or avoid unnecessary biopsies or overtreatment.

PMID- 25962738
TI  - Preparation of a poly(3'-azido-3'-deoxythymidine-co-propargyl methacrylate-co
      pentaerythritol triacrylate) monolithic column by in situ polymerization and a
      click reaction for capillary liquid chromatography of small molecules and
      proteins.
AB  - Combining free radical polymerization with click chemistry via a copper-mediated
      azide/alkyne cycloaddition (CuAAC) reaction in a "one-pot" process, a facile
      approach was developed for the preparation of a poly(3'-azido-3'-deoxythymidine
      co-propargyl methacrylate-co-pentaerythritol triacrylate) (AZT-co-PMA-co-PETA)
      monolithic column. The resulting poly(AZT-co-PMA-co-PETA) monolith showed a
      relatively homogeneous monolithic structure, good permeability and mechanical
      stability. Different ratios of monomers and porogens were used for optimizing the
      properties of a monolithic column. A series of alkylbenzenes, amides, anilines,
      and benzoic acids were used to evaluate the chromatographic properties of the
      polymer monolith in terms of hydrophobic, hydrophilic and cation-exchange
      interactions, and the results showed that the poly(AZT-co-PMA-co-PETA) monolith
      exhibited more flexible adjustment in chromatographic selectivity than that of
      the parent poly(PMA-co-PETA) and AZT-modified poly(PMA-co-PETA) monoliths. Column
      efficiencies for toluene, DMF, and formamide with 35,000-48,000 theoretical
      plates per m could be obtained at a linear velocity of 0.17 mm s(-1). The run-to
      run, column-to-column, and batch-to-batch repeatabilities of the retention
      factors were less than 4.2%. In addition, the proposed monolith was also applied
      to efficient separation of sulfonamides, nucleobases and nucleosides, anesthetics
      and proteins for demonstrating its potential.

PMID- 25962739
TI  - Preparation of the porcine secretory component and a monoclonal antibody against
      this protein.
AB  - Secretory component (SC) is a component of secretory IgA that is designated sIgA
      to distinguish it from IgA. The monoclonal antibody (MAb) against SC has been
      shown to be an excellent tool for the detection of the level of sIgA and for the
      evaluation of the efficacy of mucosal immunity. To prepare a monoclonal antibody
      against porcine SC, a recombinant porcine SC was expressed and purified. To
      develop this recombinant SC, the gene encoding the porcine SC was ligated into
      the pCold I vector. The recombinant vector was then transformed into Escherichia
      coli BL 21 (DE3), and gene expression was successfully induced by isopropyl-beta
      D-thiogalactoside (IPTG). After affinity purification with Ni-NTA resin and gel
      recovery, the recombinant SC protein was used to immunize BALB/c mice. Finally,
      three hybridoma cell lines showing specific recognitions of both recombinant SC
      and native SC were used as stable secretors of MAbs against porcine SC and were
      confirmed to have no reaction to porcine IgA or IgG. The successful preparations
      of recombinant SC protein and MAbs provide valuable materials that can be used in
      the mucosal infection diagnosis for porcine disease and mucosal immune evaluation
      for porcine vaccine, respectively.

PMID- 25962740
TI  - Expression and purification recombinant antihypertensive peptide ameliorates
      hypertension in rats with spontaneous hypertension.
AB  - A highly efficient Escherichia coli expression system was established to obtain
      an appreciable quantity of antihypertensive peptide. The DNA-coding sequence for
      the Gly-Val-Tyr-Pro-His-Lys peptide was chemically synthesized and linked to form
      a ten-copy in tandem. It was cloned into the vector pET-15b and expressed in E.
      coli BL21 (DE3). The optimal conditions for maximal expression were verified and
      included the induction time and the concentration of isopropyl-beta-D
      thiogalactopyranoside. The recombinant protein was purified by affinity
      chromatography to greater than 95% purity, and further purification was achieved
      by High-performance Liquid Chromatography after cleavage with trypsin. The
      product was identified by Electrospray Ionization-Mass Spectrometry. The
      antihypertensive effects of the recombinant AHP were investigated in
      spontaneously hypertensive rats. The in vivo results demonstrated that a single
      oral administration of this peptide in spontaneously hypertensive rats resulted
      in a significant reduction of systolic blood pressure at 2h. Systolic blood
      pressure was stabilized 4h later and remained at a low level for 24h. This study
      provides a practical method to develop the peptide into functional foods or drugs
      for the prevention and treatment of hypertension.

PMID- 25962741
TI  - Overexpression of functional human oxidosqualene cyclase in Escherichia coli.
AB  - The generation of multicyclic scaffolds from linear oxidosqualene by enzymatic
      polycyclization catalysis constitutes a cornerstone in biology for the generation
      of bioactive compounds. Human oxidosqualene cyclase (hOSC) is a membrane-bound
      triterpene cyclase that catalyzes the formation of the tetracyclic steroidal
      backbone, a key step in cholesterol biosynthesis. Protein expression of hOSC and
      other eukaryotic oxidosqualene cyclases has traditionally been performed in yeast
      and insect cells, which has resulted in protein yields of 2.7 mg protein/g cells
      (hOSC in Pichia pastoris) after 48 h of expression. Herein we present, to the
      best of our knowledge, the first functional expression of hOSC in the model
      organism Escherichia coli. Using a codon-optimized gene and a membrane extraction
      procedure for which detergent is immediately added after cell lysis, a protein
      yield of 2.9 mg/g bacterial cells was achieved after four hours of expression. It
      is envisaged that the isolation of high amounts of active eukaryotic
      oxidosqualene cyclase in an easy to handle bacterial system will be beneficial in
      pharmacological, biochemical and biotechnological applications.

PMID- 25962742
TI  - Supramolecular columnar liquid crystals formed by hydrogen bonding between a
      clicked star-shaped s-triazine and benzoic acids.
AB  - A star-shaped tris(triazolyl)triazine is shown to establish hydrogen-bond
      interactions with polycatenar benzoic acids. The formation of hydrogen-bonded
      triazine/acid complexes has been demonstrated both in solution and in bulk by
      different techniques. The complexes, mainly formed by nonmesogenic components,
      all show enantiotropic hexagonal columnar mesomorphism, which relies on the
      formation of hydrogen-bond complexes in a triazine/acid ratio of 1:3. This
      approach combines the straightforward synthesis of a nonmesomorphic triazine core
      by click chemistry, and the preparation of a supramolecular complex, providing a
      much more convenient route than covalent synthesis to modify the periphery of
      triazine discotics and thus to modulate their functionality. 

PMID- 25962743
TI  - Determinants of unmet need for family planning among currently married women in
      Dangila town administration, Awi Zone, Amhara regional state; a cross sectional
      study.
AB  - BACKGROUND: Unmet need for family planning is a major problem of developing
      countries. Evidences about unmet need for family planning and associated factors
      are not enough in Dangila town. Therefore, this study was done to assess the
      magnitude and determinants of unmet need for family planning among currently
      married women in Dangila town. METHODOLOGY: Community based cross sectional study
      design was used to collect data from a total of 551 currently married women from
      February to March 2014. Data were collected using pretested structured
      interviewer administered questionnaire after written consent was obtained from
      respondents. Collected data were edited, coded, and entered to SPSS version 16.0.
      Bivariate and multivariable logistic regression analyses were done to identify
      determinants of unmet need for family planning. RESULTS: This study revealed that
      17.4 % of married women had unmet need for family planning. In this study, women
      who were housewife/farmers were about 7 [OR = 6.81 (1.91-24.29)] times more
      likely to have unmet need compared to employed women. Women who were not
      counseled about family planning by health workers [OR = 6.76 (3.17-14.42)], women
      whose partner had non-supportive attitude for family planning use [OR = 3.34
      (1.26-8.90)] and rural women [OR = 17.65 (4.35-71.67)] were also more likely to
      have unmet need for family planning. About 33 %, 32 %, 23.5 % and 11.8 % of women
      mentioned less perceived risk of pregnancy due to breast feeding, fear of side
      effects, partner opposition and religious prohibition respectively as reasons for
      not using contraceptives at the time of interview. CONCLUSIONS: The level of
      unmet need for family planning in the study area is still high compared to the
      target set (10 %) in the national family planning guide plan of Ethiopia to be
      achieved by the end of 2015. Therefore, it is important to strengthen counseling
      and partner involvement in Dangila town to reduce unmet need for family planning.

PMID- 25962744
TI  - Does Compensating Primary Care Providers to Produce Higher Quality Make Them More
      or Less Patient Centric?
AB  - Both payment reform and patient engagement are key elements of health care
      reform. Yet the question of how incentivizing primary care providers (PCPs) on
      quality outcomes affects the degree to which PCPs are supportive of patient
      activation and patient self-management has received little attention. In this
      mixed-methods study, we use in-depth interviews and survey data from PCPs working
      in a Pioneer Accountable Care Organization that implemented a compensation model
      in which a large percentage of PCP salary is based on quality performance. We
      assess how much PCPs report focusing their efforts on supporting patient
      activation and self-management, and whether or not they become frustrated with
      patients who do not change their behaviors. The findings suggest that most PCPs
      do not see the value in investing their own efforts in supporting patient self
      management and activation. Most PCPs saw patient behavior as a major obstacle to
      improving quality and many were frustrated that patient behaviors affected their
      compensation. 

PMID- 25962746
TI  - Green tea EGCG plus fish oil omega-3 dietary supplements rescue mitochondrial
      dysfunctions and are safe in a Down's syndrome child.

PMID- 25962745
TI  - Audiometric Profiles in Autism Spectrum Disorders: Does Subclinical Hearing Loss
      Impact Communication?
AB  - Rates of hearing impairment in individuals with Autism Spectrum Disorders (ASD)
      are higher than those reported in the general population. Although ASD is not
      caused by hearing impairment, it may exacerbate symptomatology. Participants with
      ASD (N = 60) and typically developing peers (N = 16) aged 5-18 years underwent a
      comprehensive audiological screening (pure tone audiometry, uncomfortable
      loudness level, tympanometry, acoustic reflexes, distortion product otoacoustic
      emissions, and auditory brainstem response) and assessment of communication
      abilities (expressive/receptive language, articulation, phonological awareness,
      and vocal affect recognition). Incidence of abnormal findings on at least one
      measure of audiological functioning was higher for the ASD group (55%) than
      controls (14.9%) or the general population estimate (6%). The presence of sound
      sensitivity was also considerably higher for the ASD group (37%) compared with
      controls (0%) or general population estimates (8-15%). When participants with ASD
      were dichotomized into groups with and without evidence of clinical audiological
      abnormality, no significant differences were identified on measures of
      communication; however, results of correlational analyses indicated that
      variability in hearing thresholds at middle range frequencies (2000 Hz) was
      significantly related to performance on all measures of speech articulation and
      language after correction for multiple comparisons (r = -0.48 to r = -0.53, P < 
      0.0045). These findings suggest that dichotomized classification of clinical
      audiology may not be sufficient to understand the role of subclinical hearing
      loss in ASD symptomatology and that treatment studies for mild/subclinical
      hearing loss in this population may be worthwhile.

PMID- 25962747
TI  - The Effects of Aerobic and Resistance Exercise on Markers of Large Joint Health
      in Stable Rheumatoid Arthritis Patients: A Pilot Study.
AB  - OBJECTIVE: Exercise is beneficial for people with rheumatoid arthritis (RA).
      However, patients and health professionals have expressed concern about the
      possible detrimental effects of exercise on joint health. The present study
      investigated the acute and chronic effects of high-intensity, low-impact aerobic
      and resistance exercise on markers of large joint health in RA. METHODS: Eight RA
      patients and eight healthy, matched control (CTL) participants performed 30
      minutes' high-intensity, low-impact aerobic and lower-body resistance exercise,
      one week apart. Primary outcome measures assessing joint health were serum
      cartilage oligomeric matrix protein (sCOMP) and knee joint synovial inflammation
      (Doppler ultrasound colour fraction; CF). These measures were taken at baseline,
      immediately after and 0.5, one, two, six and 24 hours post-exercise. In a
      separate study, nine RA patients completed eight weeks of progressive exercise
      training. The same outcome measures were reassessed at baseline, and at one hour
      post-exercise of training weeks 0, 1, 4 and 8. RESULTS: RA patients showed higher
      overall sCOMP [RA: 1,347 +/- 421, CTL: 1,189 +/- 562 ng/mL; p < 0.05; effect size
      (ES) = 0.32] and CF when scanned longitudinally (RA: 0.489 +/- 0.30 * 10(-3) ,
      CTL: 0.101 +/- 0.13 * 10(-3) ; p < 0.01; ES = 1.73) and transversely (RA: 0.938
      +/- 0.69 * 10(-3) , CTL: 0.199 +/- 0.36 * 10(-3) ; p < 0.01; ES = 1.33) than CTL.
      However, no acute effects on joint health were observed post-exercise. Similarly,
      no chronic effects were observed over eight weeks of combined aerobic and
      resistance training in RA, with positive effects on physical fitness and
      function. CONCLUSIONS: RA patients on stable treatment with low disease activity
      were able to perform an individually prescribed high-intensity, low-impact
      aerobic and resistance exercise without changes in markers of large joint health.
      Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 25962748
TI  - Tomato plant cell death induced by inhibition of HSP90 is alleviated by Tomato
      yellow leaf curl virus infection.
AB  - To ensure a successful long-term infection cycle, begomoviruses must restrain
      their destructive effect on host cells and prevent drastic plant responses, at
      least in the early stages of infection. The monopartite begomovirus Tomato yellow
      leaf curl virus (TYLCV) does not induce a hypersensitive response and cell death
      on whitefly-mediated infection of virus-susceptible tomato plants until diseased
      tomatoes become senescent. The way in which begomoviruses evade plant defences
      and interfere with cell death pathways is still poorly understood. We show that
      the chaperone HSP90 (heat shock protein 90) and its co-chaperone SGT1 (suppressor
      of the G2 allele of Skp1) are involved in the establishment of TYLCV infection.
      Inactivation of HSP90, as well as silencing of the Hsp90 and Sgt1 genes, leads to
      the accumulation of damaged ubiquitinated proteins and to a cell death phenotype.
      These effects are relieved under TYLCV infection. HSP90-dependent inactivation of
      26S proteasome degradation and the transcriptional activation of the heat shock
      transcription factors HsfA2 and HsfB1 and of the downstream genes Hsp17 and
      Apx1/2 are suppressed in TYLCV-infected tomatoes. Following suppression of the
      plant stress response, TYLCV can replicate and accumulate in a permissive
      environment. 

PMID- 25962749
TI  - Novel transabdominal drainage of Bakri balloon following massive obstetric
      hemorrhage in a woman with cervical stenosis.

PMID- 25962750
TI  - Percutaneous CT-Guided Radiofrequency Ablation of Solitary Small Renal Masses: A
      Single Center Experience.
AB  - PURPOSE: To analyze the outcome of patients undergoing percutaneous CT-guided
      radiofrequency ablation (RFA) of small renal masses (SRM) at a single center
      during a ten-year time period. MATERIALS AND METHODS: Patient records of renal
      RFAs (07/2003 - 11/2013) were reviewed. Indications were SRM suspicious of
      malignancy on imaging and one of the following: severe comorbidity; old age;
      solitary kidney; impaired renal function; patient wish. Biopsy was performed at
      the time of RFA. Patients were excluded if no follow-up was available. Patient
      and procedural characteristics were recorded. Survival rates were calculated
      using the Kaplan-Meier's method and compared with log-rank or cox tests. RESULTS:
      38 patients (16 females, mean age 70.0 years [range 52 - 87]) presenting with a
      solitary SRM were included in the study. Biopsy showed malignancy in 29 patients;
      9 had benign tumors. 26 patients suffered from cardiovascular, respiratory or
      hepatic comorbidities. Technical success (complete ablation on first follow-up)
      was achieved in 95 % of cases. Two major complications (bowel perforation;
      hematothorax) occurred. The 3- and 7-year overall survival (OS) [any cause] rates
      were 73.4 +/- 0.8 % and 50.3 +/- 1.0 %, respectively (mean follow-up 54.6 months,
      range 1 - 127). 4 recurrences and 2 metastases were observed. The presence of
      comorbidities was the only independent predictor of OS. There was no difference
      in survival between patients with benign and malignant tumors. CONCLUSION: RFA of
      SRM is successful in a large percentage of cases with a low complication rate and
      durable local control. As RFA is typically performed in multimorbid patients,
      overall survival seems to depend primarily on comorbidities rather than cancer
      progression. Key Points * RFA of SRM is technically successful in the majority of
      cases. * RFA leads to a high degree of local tumor control. * Post-RFA most
      patients ultimately die of comorbidities. * Overall survival post-RFA does not
      significantly differ between benign and malignant tumors in multimorbid patients.

PMID- 25962751
TI  - Emphysema: Imaging for Endoscopic Lung Volume Reduction.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by two entities,
      the more airway-predominant type ("bronchitis") on the one hand, and emphysema
      predominant type on the other. Imaging via high-resolution computed tomography
      plays an important role in phenotyping COPD. For patients with advanced lung
      emphysema, new endoscopic lung volume reduction therapies (ELVR) have been
      developed. Proper selection of suitable patients requires thin-section
      reconstruction of volumetric CT image data sets also in coronal and sagittal
      orientation are required. In the current manuscript we will describe emphysema
      subtypes (centrilobular, paraseptal, panlobular), options for quantifying
      emphysema and this importance of regional distribution (homogeneous or
      heterogeneous, target area) as this is crucial for patient selection. Analysis of
      the interlobular fissures is obligatory despite the lack of standardization, as
      incomplete fissures indicate collateral ventilation (CV) via parenchymal bridges,
      which is an important criterion in choosing endoscopic methods of LVR. Every
      radiologist should be familiar with modern LVR therapies such as valves and
      coils, and furthermore should know what a lung doctor expects from radiologic
      evaluation (before and after ELVR). Finally we present a checklist as a quick
      reference for all steps concerning imaging for ELVR. KEY POINTS: * High
      resolution computed tomography with 3 D reconstructions becomes increasingly
      important in phenotyping COPD and diagnosing emphysema. * Patient selection is
      crucial for modern techniques of lung volume reduction, such as valves or coils.
      * Radiology plays a key role for fissural analysis and identifying a target area.
      * Success of this therapy depends on experience and multidisciplinary
      cooperation.

PMID- 25962752
TI  - [Spontaneous retropharyngeal hematoma with fatal outcome].

PMID- 25962753
TI  - Cluster Randomized Controlled Trial of An Aged Care Specific Leadership and
      Management Program to Improve Work Environment, Staff Turnover, and Care Quality.
AB  - OBJECTIVE: To evaluate the effectiveness of a leadership and management program
      in aged care. DESIGN: Double-blind cluster randomized controlled trial. SETTING:
      Twelve residential and community-aged care sites in Australia. PARTICIPANTS: All
      care staff employed for 6 months or longer at the aged care sites were invited to
      participate in the surveys at 3 time points: baseline (time 1), 9 months from
      baseline (time 2), and 9 months after completion of time 2 (time 3) from 2011 to
      2013. At each time point, at least 500 care staff completed a survey. At baseline
      (N = 503) the largest age group was 45 to 54 years (37%), and the majority of
      care staff were born in Australia (70%), spoke English (94%), and had at least
      completed secondary education (57%). INTERVENTION: A 12-month Clinical Leadership
      in Aged Care (CLiAC) program for middle managers, which aimed to further develop
      their leadership and management skills in creating positive workplace
      relationships and in enabling person-centered, evidence-based care. MAIN OUTCOME
      MEASURES: The primary outcomes were care staff ratings of the work environment,
      care quality and safety, and staff turnover rates. Secondary outcomes were care
      staff's intention to leave their employer and profession, workplace stress, job
      satisfaction, and cost-effectiveness of implementing the program. Absenteeism was
      excluded due to difficulty in obtaining reliable data. Managers' self-rated
      knowledge and skills in leadership and management are not included in this
      article, which focuses on care staff perceptions only. RESULTS: At 6 months after
      its completion, the CLiAC program was effective in improving care staff's
      perception of management support [mean difference 0.61, 95% confidence interval
      (CI) 0.04-1.18; P = .04]. Compared with the control sites, care staff at the
      intervention sites perceived their managers' leadership styles as more
      transformational (mean difference 0.30, 95% CI 0.09-0.51; P = .005),
      transactional (mean difference 0.22, 95% CI 0.05-0.39; P = .01), and less passive
      avoidant (mean difference 0.30, 95% CI 0.07-0.52; P = .01); and were rated higher
      on the overall leadership outcomes (mean difference 0.35, 95% CI 0.13-0.56; P =
      .001) as well as individual manager outcomes: extra effort (P = .004),
      effectiveness (P = .001), and satisfaction (P = .01). There was no evidence that
      CLiAC was effective in reducing staff turnover, or improving patient care quality
      and safety. CONCLUSIONS: While the CLiAC leadership program had direct impact on
      the primary process outcomes (management support, leadership actions, behaviors,
      and effects), this was insufficient to change the systems required to support
      care service quality and client safety. Nevertheless, the findings send a strong
      message that leadership and management skills in aged care managers can be
      nurtured and used to change leadership behaviors at a reasonable cost.

PMID- 25962754
TI  - Cre-driven optogenetics in the heterogeneous genetic panorama of the VTA.
AB  - The selectivity of optogenetics commonly relies on genetic promoters to
      manipulate specific populations of neurons through the use of Cre-driver lines.
      All studies performed in the ventral tegmental area (VTA) so far have utilized
      promoters present in groups of cells that release dopamine (DA), GABA, or
      glutamate. However, neurons that co-release neurotransmitters and variabilities
      within groups of neurons that release the same neurotransmitter present
      challenges when evaluating the results. Further complexity is introduced by
      ectopic expression patterns often occurring in transgenic Cre-drivers. New
      perspectives could be unfolded by identifying and selecting different types of
      promoter for driving the Cre recombinase. Here, we discuss some promising
      candidates and highlight the advantages or disadvantages of different methods for
      creating novel transgenic lines. 

PMID- 25962756
TI  - Biofunction-assisted aptasensors based on ligand-dependent 3' processing of a
      suppressor tRNA in a wheat germ extract.
AB  - We have developed a novel type of biofunction-assisted aptasensor that harnesses
      ligand-dependent 3' processing of a premature amber suppressor tRNA and the
      subsequent amber suppression of a reporter gene in a wheat germ extract. 

PMID- 25962755
TI  - Cantharidin inhibits cell proliferation and promotes apoptosis in tongue squamous
      cell carcinoma through suppression of miR-214 and regulation of p53 and Bcl
      2/Bax.
AB  - Cantharidin, a type of terpenoid, is a chemical compount secreted by the blister
      beetle or Mylabris phelarata pallas of the Meloidae family. Cantharidin is known
      to have good antitumor activity. The present study aimed to investigate the
      anticancer effect of cantharidin and its possible underlying mechanism using
      tongue squamous cell carcinoma (TSCC) TCA8113 cells. TCA8113 cells were treated
      with various concentrations of cantharidin, and the cell viability and
      cytotoxicity were assessed using MTT and LDH assays, respectively. Flow cytometry
      was conducted to examine cell apoptosis and colorimetric protease assay was
      performed to analyze caspase-9/3 activities in TCA8113 cells. qPCR and western
      blot analysis were used to investigate microRNA-214 (miR-214) expression, as well
      as the expression of p53, Bcl-2 and Bax proteins in TCA8113 cells. miR-214 and
      anti-miR-214 were transfected with mimics to examine whether miR-214 expression
      regulated the anticancer effect of cantharidin on TCA8113 cells and p53, Bcl-2
      and Bax protein expression. The anticancer effect of cantharidin significantly
      inhibited cell proliferation and increased cytotoxicity of TSCC Tca8113 cells in
      a dose- and time-dependent manner. In addition, cantharidin induced cell
      apoptosis and activated caspase-9/3 activities of TSCC Tca8113 cells. Cantharidin
      markedly weakened miR-214 expression level, activated p53 protein expression, and
      suppressed the Bcl-2/Bax signaling pathway in Tca8113 cells. Downregulation of
      miR-214 increased p53 protein expression and decreased the Bcl-2/Bax signaling
      pathway of TSCC Tca8113 cells. However, the overexpression of miR-214 reduced the
      anticancer effect of cantharidin on the proliferation and apoptosis of TSCC
      Tca8113 cells, inhibited p53 protein expression, and increased the Bcl-2/Bax
      signaling pathway. The results suggested that cantharidin is a potential
      anticancer drug that can be used to regulate the proliferation and apoptosis of
      human TSCC Tca8113 cells. Additionally, its mechanism may partially be associated
      with the downregulation of miR-214, upregulation of p53 protein expression and
      suppression of the Bcl-2/Bax signaling pathway. 

PMID- 25962757
TI  - Low-temperature direct copper-to-copper bonding enabled by creep on (111)
      surfaces of nanotwinned Cu.
AB  - Direct Cu-to-Cu bonding was achieved at temperatures of 150-250  degrees C using
      a compressive stress of 100 psi (0.69 MPa) held for 10-60 min at 10(-3) torr. The
      key controlling parameter for direct bonding is rapid surface diffusion on (111)
      surface of Cu. Instead of using (111) oriented single crystal of Cu, oriented
      (111) texture of extremely high degree, exceeding 90%, was fabricated using the
      oriented nano-twin Cu. The bonded interface between two (111) surfaces forms a
      twist-type grain boundary. If the grain boundary has a low angle, it has a
      hexagonal network of screw dislocations. Such network image was obtained by plan
      view transmission electron microscopy. A simple kinetic model of surface creep is
      presented; and the calculated and measured time of bonding is in reasonable
      agreement. 

PMID- 25962758
TI  - Traffic-related air pollution and the incidence of childhood central nervous
      system tumors: Texas, 2001-2009.
AB  - BACKGROUND: Due to increasing concerns regarding air pollution and childhood
      cancer, we conducted a population-based study evaluating the association between
      traffic-related hazardous air pollutants (1,3-butadiene, benzene, diesel
      particulate matter [DPM]) and the incidence of childhood central nervous system
      (CNS) tumors. PROCEDURE: Information on children diagnosed with a CNS tumor at
      <15 years of age, in Texas, for the period of 2001-2009 (n = 1,949) was obtained
      from the Texas Cancer Registry. Information on the corresponding at-risk
      population was obtained from the United States (U.S.) Census. Annual census tract
      level pollutant concentrations, estimated by the U.S. Environmental Protection
      Agency, were categorized based on quartiles (low, medium, medium-high, and high)
      of the statewide distribution. Multivariable Poisson regression was used to
      calculate adjusted incidence rate ratios (aIRR). Juvenile pilocytic astrocytomas
      (JPAs) (n = 384), other astrocytomas (n = 372), ependymomas (n = 142),
      medulloblastomas (n = 235), and primitive neuroectodermal tumors (PNET) (n = 47)
      were evaluated. RESULTS: Census tracts with medium and medium-high 1,3-butadiene
      concentrations had higher astrocytoma incidence rates (aIRR [95% confidence
      interval (CI)]: 1.46 [1.05-2.01] and 1.69 [1.22-2.33], respectively) compared
      with low concentrations. Census tracts with medium DPM concentrations had higher
      astrocytoma (aIRR [95%CI]: 1.42 [1.05-1.94]) and medulloblastoma (aIRR [95%CI]:
      1.46 [1.01-2.12]) incidence rates compared with low concentrations. Increased
      concentrations of 1,3-butadiene and benzene were strongly associated with
      increased PNET incidence rates, but were not statistically significant. No
      associations were detected with JPA or ependymoma incidence. CONCLUSIONS: In one
      of the largest studies of its kind, our results suggest positive associations
      between hazardous air pollutants and incidence of astrocytoma (1,3-butadiene and
      DPM) and medulloblastoma (DPM).

PMID- 25962759
TI  - Generation and propagation of recombinant mumps viruses exhibiting an additional
      U residue in the homopolymeric U tract of the F gene-end signal.
AB  - As a member of the family paramyxoviridae, subfamily paramyxovirinae, the genome
      of mumps virus (MuV) is postulated to be polyhexameric in length in order to be
      able to replicate efficiently. While all natural MuV strains sequenced so far
      obey to this "rule of six," we describe here the isolation of recombinant MuVs
      that appeared to contain an additional U residue in the homopolymeric tract of
      the F gene-end signal, resulting in a genome length of 6n + 1. Sequencing of
      several plaque-purified viruses from these preparations did not reveal the
      existence of length-correcting mutations, suggesting that they are violators of
      the rule of six. Employing high-throughput sequencing technology, we provide
      evidence that the insertion of an additional U residue is mainly the result of
      the rescue system used that relies on T7 RNA polymerase. Limited in vitro and in
      vivo testing of the viruses did not reveal any significant impact of the longer
      genome on virus replication or virulence, suggesting that the rule of six is not
      a strict requirement for MuV replication.

PMID- 25962761
TI  - Contemporary Cardiovascular Concerns after Spinal Cord Injury: Mechanisms,
      Maladaptations, and Management.
AB  - Cardiovascular (CV) issues after spinal cord injury (SCI) are of paramount
      importance considering they are the leading cause of death in this population.
      Disruption of autonomic pathways leads to a highly unstable CV system, with
      impaired blood pressure (BP) and heart rate regulation. In addition to low
      resting BP, on a daily basis the majority of those with SCI suffer from transient
      episodes of aberrantly low and high BP (termed orthostatic hypotension and
      autonomic dysreflexia, respectively). In fact, autonomic issues, including
      resolution of autonomic dysreflexia, are frequently ranked by individuals with
      high-level SCI to be of greater priority than walking again. Owing to a
      combination of these autonomic disturbances and a myriad of lifestyle factors,
      the pernicious process of CV disease is accelerated post-SCI. Unfortunately,
      these secondary consequences of SCI are only beginning to receive appropriate
      clinical attention. Immediately after high-level SCI, major CV abnormalities
      present in the form of neurogenic shock. After subsiding, new issues related to
      BP instability arise, including orthostatic hypotension and autonomic
      dysreflexia. This review describes autonomic control over the CV system before
      injury and the mechanisms underlying CV abnormalities post-SCI, while also
      detailing the end-organ consequences, including those of the heart, as well as
      the systemic and cerebral vasculature. The tertiary impact of CV dysfunction will
      also be discussed, such as the potential impediment of rehabilitation, and
      impaired cognitive function. In the recent past, our understanding of autonomic
      dysfunctions post-SCI has been greatly enhanced; however, it is vital to further
      develop our understanding of the long-term consequences of these conditions,
      which will equip us to better manage CV disease morbidity and mortality in this
      population. 

PMID- 25962760
TI  - Genome-wide association analyses for meat quality traits in Chinese Erhualian
      pigs and a Western Duroc * (Landrace * Yorkshire) commercial population.
AB  - BACKGROUND: Understanding the genetic mechanisms that underlie meat quality
      traits is essential to improve pork quality. To date, most quantitative trait
      loci (QTL) analyses have been performed on F2 crosses between outbred pig strains
      and have led to the identification of numerous QTL. However, because linkage
      disequilibrium is high in such crosses, QTL mapping precision is unsatisfactory
      and only a few QTL have been found to segregate within outbred strains, which
      limits their use to improve animal performance. To detect QTL in outbred pig
      populations of Chinese and Western origins, we performed genome-wide association
      studies (GWAS) for meat quality traits in Chinese purebred Erhualian pigs and a
      Western Duroc * (Landrace * Yorkshire) (DLY) commercial population. METHODS:
      Three hundred and thirty six Chinese Erhualian and 610 DLY pigs were genotyped
      using the Illumina PorcineSNP60K Beadchip and evaluated for 20 meat quality
      traits. After quality control, 35 985 and 56 216 single nucleotide polymorphisms
      (SNPs) were available for the Chinese Erhualian and DLY datasets, respectively,
      and were used to perform two separate GWAS. We also performed a meta-analysis
      that combined P-values and effects of 29 516 SNPs that were common to Erhualian,
      DLY, F2 and Sutai pig populations. RESULTS: We detected 28 and nine suggestive
      SNPs that surpassed the significance level for meat quality in Erhualian and DLY
      pigs, respectively. Among these SNPs, ss131261254 on pig chromosome 4 (SSC4) was
      the most significant (P = 7.97E-09) and was associated with drip loss in
      Erhualian pigs. Our results suggested that at least two QTL on SSC12 and on SSC15
      may have pleiotropic effects on several related traits. All the QTL that were
      detected by GWAS were population-specific, including 12 novel regions. However,
      the meta-analysis revealed seven novel QTL for meat characteristics, which
      suggests the existence of common underlying variants that may differ in frequency
      across populations. These QTL regions contain several relevant candidate genes.
      CONCLUSIONS: These findings provide valuable insights into the molecular basis of
      convergent evolution of meat quality traits in Chinese and Western breeds that
      show divergent phenotypes. They may contribute to genetic improvement of
      purebreds for crossbred performance.

PMID- 25962762
TI  - Coexistence and survival of pathogenic leptospires by formation of biofilm with
      Azospirillum.
AB  - Pathogenic Leptospira spp. represent one cause of leptospirosis worldwide and
      have long been regarded as solitary organisms in soil and aquatic environments.
      However, in the present study, Leptospira interrogans was observed to be
      associated with environmental biofilms with 21 bacterial isolates belonging to 10
      genera. All 21 isolates were examined for their coaggregation and biofilm-forming
      ability with leptospires in vitro. Among these, Azospirillum brasilense RMRCPB
      showed maximum interspecies coaggregation with leptospiral strains (>75%, visual
      score of +4). Other significant coaggregating isolates belonged to the genera
      Sphingomonas, Micrococcus, Brevundimonas, Acinetobacter and Paracoccus. Biofilms
      of leptospires in combination with A. brasilense RMRCPB showed high resistance to
      penicillin G, ampicillin and tetracycline (minimum bactericidal concentration
      >=800 MUg/mL) and tolerance to UV radiation and high temperature (up to 49
      degrees C). This study hypothesized that biofilm formation with A. brasilense
      protects the pathogenic Leptospira from adverse environmental conditions/stress.
      This coexistence of pathogenic Leptospira with other bacteria may be the key
      factor for its persistence and survival. However, the mechanism of biofilm
      formation by leptospires needs to be explored to help devise an appropriate
      control strategy and reduce transmission of leptospires.

PMID- 25962763
TI  - Environmental drivers of the distribution of nitrogen functional genes at a
      watershed scale.
AB  - To date only few studies have dealt with the biogeography of microbial
      communities at large spatial scales, despite the importance of such information
      to understand and simulate ecosystem functioning. Herein, we describe the
      biogeographic patterns of microorganisms involved in nitrogen (N)-cycling
      (diazotrophs, ammonia oxidizers, denitrifiers) as well as the environmental
      factors shaping these patterns across the Koiliaris Critical Zone Observatory, a
      typical Mediterranean watershed. Our findings revealed that a proportion of
      variance ranging from 40 to 80% of functional genes abundance could be explained
      by the environmental variables monitored, with pH, soil texture, total organic
      carbon and potential nitrification rate being identified as the most important
      drivers. The spatial autocorrelation of N-functional genes ranged from 0.2 to 6.2
      km and prediction maps, generated by cokriging, revealed distinct patterns of
      functional genes. The inclusion of functional genes in statistical modeling
      substantially improved the proportion of variance explained by the models, a
      result possibly due to the strong relationships that were identified among
      microbial groups. Significant relationships were set between functional groups,
      which were further mediated by land use (natural versus agricultural lands).
      These relationships, in combination with the environmental variables, allow us to
      provide insights regarding the ecological preferences of N-functional groups and
      among them the recently identified clade II of nitrous oxide reducers.

PMID- 25962764
TI  - Menopausal hormone therapy and mortality among endometrial cancer patients in the
      NIH-AARP Diet and Health Study.
AB  - BACKGROUND: While menopausal hormone therapy (MHT) is an established endometrial
      cancer risk factor, its relationship with mortality among endometrial cancer
      patients is understudied. METHODS: Within the NIH-AARP Diet and Health Study, we
      examined the associations of pre-diagnosis MHT use with 10-year all-cause and
      endometrial cancer-specific mortality among 890 endometrial cancer patients. We
      used Cox proportional hazards regression models to estimate hazard ratios (HRs)
      and 95 % confidence intervals (CIs) adjusted for tumor characteristics,
      treatment, and other risk factors. RESULTS: Endometrial cancer cases were
      diagnosed a median of 4.6 years (range 0.0-10.1 years) after the second risk
      factor questionnaire was completed. We identified a total of 241 deaths, of which
      104 were due to endometrial cancer. Compared with non-MHT use, pre-diagnosis use
      of estrogen plus progestin therapy (EPT)-only was associated with lower 10-year
      all-cause (HR 0.65, 95 % CI 0.43-0.99, based on 29 deaths) and endometrial cancer
      specific mortality (HR 0.51, 95 % CI 0.26-0.98, based on 11 deaths). Recency of
      MHT use, assessed approximately 5 years prior to the endometrial cancer
      diagnosis, was associated with mortality. Compared with non-MHT users, former ET
      users had higher all-cause (HR 1.71, 95 % CI 1.02-2.88, based on 18 deaths) and
      endometrial cancer-specific mortality (HR 2.17, 95 % CI 0.96-4.90, based on 8
      deaths), whereas current EPT users had nonsignificant lower risks of death.
      CONCLUSION: Based on small numbers, we observed that pre-diagnosis use of EPT was
      related to lower mortality among endometrial cancer patients. Future studies
      examining the biological mechanisms underlying this association are warranted.

PMID- 25962765
TI  - TNF-related apoptosis-inducing ligand and cardiovascular disease in rheumatoid
      arthritis.
AB  - OBJECTIVES: We examined the association of TNF-related apoptosis-inducing ligand
      (TRAIL) concentrations with cardiovascular disease (CVD) in rheumatoid arthritis
      (RA) and, since osteoprotegerin (OPG) can act as a decoy receptor for TRAIL,
      whether TRAIL concentrations impact on the OPG level-atherosclerotic CVD relation
      that was recently documented in the present cohort. METHODS: TRAIL concentrations
      were assessed by ELISA in 151 RA patients of which 75 (49.7%) had CVD comprising
      ischaemic heart disease (n=27), cerebrovascular accident (n=26), peripheral
      artery disease (n=9) or/and heart failure (HF) (n=27), and 62 controls. RESULTS:
      Mean RA duration was 12 years. In RA patients, C-reactive protein (CRP) levels
      and cholesterol-HDL cholesterol ratio related to TRAIL concentrations [partial R=
      0.222 (p=0.006) and 0.174 (p=0.04), respectively]. TRAIL concentrations were
      smaller in RA patients compared to controls (median (interquartile range) = 80.2
      (60.9-120.4) versus 130.4 (89.4-167.7) pg/ml, p<0.0001)). TRAIL levels were
      larger in RA patients with compared to those without HF (105.5 (66.5-143.4)
      versus 79.9 (57.8-110.6), p=0.02); this difference was independent of demographic
      characteristics and traditional cardiovascular risk factors (p=0.04) but not CRP
      concentrations (p=0.1). TRAIL levels were consistently unrelated to
      atherosclerotic CVD. Our previously reported OPG-atherosclerotic CVD relation in
      RA survived adjustment for TRAIL concentrations in a mixed regression model
      (p=0.04). CONCLUSIONS: TRAIL concentrations are markedly reduced and associated
      with HF in established RA, this relationship being explained by CRP levels. OPG
      may directly enhance CVD risk in RA.

PMID- 25962766
TI  - Transfusion e-learning for junior doctors: the educational role of
      'LearnBloodTransfusion'.
AB  - OBJECTIVES: To critically analyse the educational role of 'LearnBloodTransfusion'
      (LBT) in enabling junior doctors to be safe transfusion practitioners.
      BACKGROUND: Computer assisted learning, or e-learning, enables the educational
      needs of learners to be flexibly met. Education and learning in the health
      service is necessary to ensure appropriate skills, behaviours and training are
      provided, to assure excellence in healthcare delivery. LBT is a computer-assisted
      learning programme that has been designed to meet the needs of practitioners
      involved in the transfusion process. It is widely adopted across the NHS and
      within undergraduate medical training. METHOD: Critical analysis of LBT relating
      to learning outcomes, assessment tools and functionality, as pertaining to the
      transfusion curriculum for junior doctors. RESULTS: Learning outcomes of LBT
      adhere to Bloom's taxonomy, addressing cognitive, psycho-motor and affective
      domains of learning. LBT flexibly meets differing styles, strategies and levels
      of learning although there is scope to enhance the computer-facilitated
      flexibility of this learning tool. LBT is unable to address the complex clinical
      reasoning skills or clinical competency required by doctors in the transfusion
      process. CONCLUSION: LBT uses effective educational methodology to deliver the
      transfusion curriculum to junior doctors although LBT must be complemented by
      additional methods of learning to ensure clinical competency.

PMID- 25962767
TI  - Correction: Influence of N-heteroaromatic pi-pi stacking on supramolecular
      assembly and coordination geometry; effect of a single-atom change in the ligand.

PMID- 25962768
TI  - Development of a Functional Ruthenium(II) Complex that Can Act as a
      Photoluminescent and Electrochemiluminescent Dual-signaling Probe for
      Hypochlorous Acid.
AB  - A functional ruthenium(II) complex that can act as a probe for response to
      hypochlorous acid (HOCl) in aqueous media with photoluminescence (PL) and
      electrochemiluminescence (ECL) dual-signals, [Ru(bpy)2(DB-phen)](PF6)2 [bpy: 2,2'
      bipyridine; DB-phen: 5-(2,4-dimethoxybenzylamino)-1,10-phenanthroline)], has been
      designed and synthesized. The complex is highly luminescent both under the light
      excitation and the electrochemical induction. It can specifically react with HOCl
      in physiological pH aqueous media to afford its chlorinated derivative,
      [Ru(bpy)2(DBCA-phen)](PF6)2 [DBCA-phen: 5-(2,4-dimethoxybenzyl-chloroamino)- 1,10
      phenanthroline], accompanied by remarkable decreases in its PL and ECL
      intensities. The PL and ECL abatements of [Ru(bpy)2(DB-phen)](PF6)2 show good
      linear correlation to the concentration of HOCl with detection limits at low
      micromolar concentration level, and the PL and ECL responses of the complex to
      HOCl are highly specific without interferences of other reactive oxygen/nitrogen
      species. These features enabled [Ru(bpy)2(DB-phen)](PF6)2 to be used as a probe
      for the highly selective and sensitive detection of HOCl in aqueous media with PL
      and ECL dual-modes. 

PMID- 25962769
TI  - Primaquine dosing errors: the human cost of a pharmaceutical anachronism.
AB  - Confusion between salt/base forms of primaquine may result in malaria prophylaxis
      failure. During 1995-2011, there were 14 malaria cases in Israel despite
      primaquine primary prophylaxis. In 6/14 cases, primaquine was underdosed because
      of confusion between salt and base forms, including two Plasmodium falciparum
      cases. Primaquine labeling clarification may be lifesaving. 

PMID- 25962770
TI  - Geostatistical modeling of malaria endemicity using serological indicators of
      exposure collected through school surveys.
AB  - Ethiopia has a diverse ecology and geography resulting in spatial and temporal
      variation in malaria transmission. Evidence-based strategies are thus needed to
      monitor transmission intensity and target interventions. A purposive selection of
      dried blood spots collected during cross-sectional school-based surveys in Oromia
      Regional State, Ethiopia, were tested for presence of antibodies against
      Plasmodium falciparum and P. vivax antigens. Spatially explicit binomial models
      of seroprevalence were created for each species using a Bayesian framework, and
      used to predict seroprevalence at 5 km resolution across Oromia. School
      seroprevalence showed a wider prevalence range than microscopy for both P.
      falciparum (0-50% versus 0-12.7%) and P. vivax (0-53.7% versus 0-4.5%),
      respectively. The P. falciparum model incorporated environmental predictors and
      spatial random effects, while P. vivax seroprevalence first-order trends were not
      adequately explained by environmental variables, and a spatial smoothing model
      was developed. This is the first demonstration of serological indicators being
      used to detect large-scale heterogeneity in malaria transmission using samples
      from cross-sectional school-based surveys. The findings support the incorporation
      of serological indicators into periodic large-scale surveillance such as Malaria
      Indicator Surveys, and with particular utility for low transmission and
      elimination settings. 

PMID- 25962771
TI  - Detection of mixed-species infections of Plasmodium falciparum and Plasmodium
      vivax by nested PCR and rapid diagnostic tests in southeastern Iran.
AB  - Coexistence of two species of Plasmodium in a single host has disrupted the
      diagnosis and treatment of malaria. This study was designed to evaluate the
      ability of rapid diagnostic test (RDT) kits for the diagnosis of mixed-species
      malaria infections in southeastern Iran. A total of 100 malaria patients were
      included in the study out of 164 randomly suspected symptomatic malaria patients
      from May to November 2012. Nested polymerase chain reaction (PCR) was also used
      to judge the ability of microscopy versus RDT kits for detecting mixed species.
      The sensitivity of light microscopy for the detection of mixed-species malaria
      infections was 16.6% (95% confidence interval [CI] = 3-49.1). Nested PCR revealed
      12 patients with mixed-species infection. The CareStart Pv/Pf Combo kit detected
      58% of the mixed-species infections, which were determined by nested PCR
      (sensitivity = 58.3%; 95% CI = 28.5-83.5). For identifying P. falciparum, P.
      vivax, and mixed-species infections, the concordance rates (kappa statistics) of
      microscopy and CareStart Pv/Pf Combo kit with nested PCR were 0.76 and 0.79,
      respectively (P = 0.001). This study underlines the effectiveness of RDT kits to
      improve the differentiation of mixed-species malaria infections in endemic areas
      where the prevalence of chloroquine resistance is high. 

PMID- 25962772
TI  - Comparison of Fluorescence Microscopy and Different Growth Media Culture Methods
      for Acanthamoeba Keratitis Diagnosis.
AB  - Acanthamoeba keratitis (AK), a potentially blinding infection of the cornea, is
      caused by a free-living protozoan. Culture and microscopic examination of corneal
      scraping tissue material is the conventional method for identifying Acanthamoeba.
      In this article, we compared several methods for AK diagnosis of 32 patients:
      microscopic examination using fluorescent dye, specific culture on growth media
      non-nutrient agar (NNA), culture on liquid growth media-peptone yeast glucose
      (PYG), and TYI-S-33. AK was found in 14 patients. Thirteen of the specimens were
      found AK positive by fluorescence microscopic examination, 11 specimens were
      found AK positive on PYG growth media, and 9 specimens were found AK positive on
      TYI-S-33 growth media. Only five specimens were found AK positive on NNA growth
      media. Therefore, we recommend using fluorescence microscopy technique and
      culture method, especially PYG liquid media. 

PMID- 25962773
TI  - Temperature and the field stability of a dengue rapid diagnostic test in the
      tropics.
AB  - The global incidence of dengue has increased significantly in recent decades,
      resulting in a large public health burden in tropical and subtropical countries.
      Dengue rapid diagnostic tests (RDTs) can provide accurate, rapid accessible
      diagnosis for patient management and may be easily used by health workers in
      rural areas. However, in dengue-endemic areas, ambient temperatures are often
      higher than manufacturer's recommendation. We therefore evaluated the effect of
      high temperature over time on the performance of one commonly used dengue RDT,
      the Standard Diagnostics Bioline Dengue Duo. RDTs were kept in five different
      conditions (at 4 degrees C, 35 degrees C, 45 degrees C, 60 degrees C, and at
      fluctuant ambient temperatures in a free-standing hut) for between 2 days and 2
      years in the Lao People's Democratic Republic (PDR). RDTs were tested with four
      control sera (negative, dengue nonstructural protein 1 [NS1], anti-dengue
      immunoglobulin [Ig] M, and anti-dengue IgG positive). The RDTs had 100%
      consistency over the 2-year study, despite high temperatures, including in the
      hut in which temperatures exceeded the manufacturer's recommendations for 29% of
      time points. These data suggest that the diagnostic accuracy of the SD Bioline
      Dengue Duo RDT remains stable even after long-term storage at high temperatures.
      Therefore, use at such ambient temperatures in tropical areas should not
      jeopardize the dengue diagnostic outcome. 

PMID- 25962775
TI  - Rotavirus group A genotypes detected through diarrheal disease surveillance in
      Haiti, 2012.
AB  - Samples collected in 2012 through diarrheal disease surveillance in Haiti were
      tested for rotavirus by enzyme immunoassay and real time RT-PCR and positive
      samples were genotyped. The predominant genotypes were G1P[8] (29% prevalence)
      and G9P[8] (21%). The observed genotype prevalence was similar to that reported
      previously for other Caribbean countries. 

PMID- 25962774
TI  - Emergence of a new lineage of Cache Valley virus (Bunyaviridae: Orthobunyavirus)
      in the Northeastern United States.
AB  - Cache Valley virus (CVV; Family Bunyavidae, Genus Orthobunyavirus) is a mosquito
      borne zoonosis that frequently infects humans and livestock in North and Central
      America. In the northeastern United States, CVV transmission is unpredictable
      from year-to-year and may derive from the periodic extinction and reintroduction
      of new virus strains into this region. To evaluate this possibility, we sequenced
      and analyzed numerous CVV isolates sampled in Connecticut during an 18-year
      period to determine how the virus population may change over time. Phylogenetic
      analyses showed the establishment of a new viral lineage during 2010 that became
      dominant by 2014 and appears to have originated from southern Mexico. CVV strains
      from Connecticut also grouped into numerous sub-clades within each lineage that
      included viruses from other U.S. states and Canada. We did not observe the
      development and stable persistence of local viral clades in Connecticut, which
      may reflect the episodic pattern of CVV transmission. Together, our data support
      the emergence of a new lineage of CVV in the northeastern United States and
      suggest extensive dispersal of viral strains in North America. 

PMID- 25962777
TI  - Googling for Information About Alternative Vaccination Schedules.
AB  - INTRODUCTION: The purpose of this study was to explore and describe the
      information a parent may find when Googling for information about alternative
      vaccination schedules. METHODS: The data collection tool included evaluation of
      Web site quality and vaccine-specific content on the 12 sites that met the
      inclusion criteria. RESULTS: Seven of the Web sites had a bias toward
      vaccination, three sites were anti-vaccine, and two sites were neutral in their
      stance. Three of the four Web sites authored by physicians had an antivaccine
      bias. Only three sites included 50% or more of the vaccine-specific content.
      Fewer than half of the Web sites recommended that vaccine concerns be discussed
      with a health care provider. Three alternate vaccine schedules were found in the
      study sample. DISCUSSION: Although the majority of the Web sites indicated that
      vaccines are important and acknowledged that parents may have legitimate concerns
      regarding vaccinations, few addressed parental fears surrounding vaccine safety.
      It would be challenging for a parent to decide what vaccine information
      constitutes "science" and which site is "right" when there are "expert"
      physicians on both sides of an intense debate. It is important for parents to
      bring in the vaccine information they find to facilitate an open dialogue and
      build trust with their health care provider.

PMID- 25962776
TI  - Assessing drivers of full adoption of test and treat policy for malaria in
      Senegal.
AB  - Malaria treatment policy has changed from presumptive treatment to targeted "test
      and treat" (T&T) with malaria rapid diagnostic tests (RDTs) and artemisinin
      combination therapy (ACT). This transition involves changing behavior among
      health providers, meaning delays between introduction and full implementation are
      recorded in almost every instance. We investigated factors affecting successful
      transition, and suggest approaches for accelerating uptake of T&T. Records from
      2000 to 2011 from health clinics in Senegal where malaria is mesoendemic were
      examined (96,166 cases). The study period encompassed the implementation of
      national T&T policy in 2006. Analysis showed that adherence to test results is
      the first indicator of T&T adoption and is dependent on accumulation of
      experience with positive RDTs (odds ratio [OR]: 0.55 [P <= 0.001], 95% confidence
      interval [CI]: 0.53-0.58). Reliance on tests for malaria diagnosis (rather than
      presumptive diagnosis) followed after test adherence is achieved, and was also
      associated with increased experience with positive RDTs (OR: 0.60 [P <= 0.001],
      95% CI: 0.58-0.62). Logistic models suggest that full adoption of T&T clinical
      practices can occur within 2 years, that monitoring these behavioral responses
      rather than RDT or ACT consumption will improve evaluation of T&T uptake, and
      that accelerating T&T uptake by focusing training on adherence to test results
      will reduce overdiagnosis and associated health and economic costs in mesoendemic
      regions. 

PMID- 25962778
TI  - Anti-NMDA Receptor Encephalitis: A Case Study of Recovery Through Art.

PMID- 25962779
TI  - Dynamic Monitoring of MicroRNA-DNA Hybridization Using DNAase-Triggered Signal
      Amplification.
AB  - Dynamically monitoring microRNA (miRNA)-DNA reactions is critical for elucidating
      various biological processes. However, traditional strategies fail to capture
      this dynamic event because the original targets are preamplified. In the present
      study, we developed an amplification-free strategy for real-time monitoring of
      miRNA-DNA hybridization that integrates the advantages of both duplex-specific
      nuclease (DSN)-triggered signal amplification and single-stranded DNA probe
      coating facilitated by reduced graphene oxide. DSN-mediated miRNA recognition was
      found to consist of two phases: hybridization and hybridization cleavage. In the
      presence of miRNA and DSN, hybridization of a 22-mer miRNA-DNA could be completed
      within 7 min by observing the angle increase in a surface plasmon resonance (SPR)
      biosensor. The subsequent hybridization-cleavage process could be visualized as a
      gradual SPR angle decrease that occurred until all coated probes were hydrolyzed.
      In addition, for miRNA-21 detection, the proposed linear signal amplification
      assay demonstrated a sensitivity of 3 fM over a dynamic range of 5 orders of
      magnitude. 

PMID- 25962780
TI  - A returning migrant worker with avian influenza A (H7N9) virus infection in
      Guizhou, China: a case report.
AB  - INTRODUCTION: Human infection with avian influenza A (H7N9) virus was first
      reported on March, 2013 in the Yangtze River Delta region of China. The majority
      of human cases were detected in mainland China; other regions out of mainland
      China reported imported human cases, including Hong Kong SAR, Taiwan (the
      Republic of China) and Malaysia, due to human transportation. Here, we report the
      first human case of H7N9 infection imported into Guizhou Province during the
      Spring Festival travel season in January 2014. CASE PRESENTATION: In early
      January 2014, a 38-year-old healthy Chinese man, a migrant worker returning from
      previously H7N9-affected Zhejiang Province, was identified as the first human
      case of infection with avian influenza A(H7N9) virus in Guizhou Province. He
      developed fever in Zhejiang at the beginning of January 2014, and returned to
      Guizhou for the Chinese New Year the next day. He went to seek medical care, but
      deteriorated rapidly and died on day 8 after his illness onset. The influenza
      virus A/Guizhou/01502/2014 isolated from the patient had 99% identity with
      viruses circulating in the Yangtze River Delta region. Selected amino acids
      substitutions, well-known to be associated with mammalian adaptation, viral
      replication and drug resistance were similar to other H7N9 viruses circulating in
      humans. CONCLUSIONS: Epidemiology investigation and laboratory results confirmed
      it was the first imported case of H7N9 infection in Guizhou Province. This
      finding further indicated that more human H7N9 cases may be detected in other
      regions due to frequent travel both domestically and internationally.

PMID- 25962781
TI  - Cameroon public health sector: shortage and inequalities in geographic
      distribution of health personnel.
AB  - INTRODUCTION: Cameroon is classified by the World Health Organization (WHO) as
      having a critical shortage of health personnel. This is further complicated by
      the geographic distributional inequalities of the national health workforce. This
      shortfall impedes Cameroons' progress of improving the human resources for health
      (HRH) to meet up with the Millennium Development Goals (MDGs) by 2015. However,
      it is unknown whether the health workforce of Cameroon is distributed equally
      across geographic regions. Additionally, indicators other than population levels
      have not been used to measure health care needs. This study aimed to assess the
      adequacy, evenness of distribution and challenges faced by the health workforce
      across the different regions of Cameroon. METHODS: National health personnel
      availability and distribution were assessed by use of end-of-year census data for
      2011 obtained from the MoPH data base. The inequalities and distribution of the
      workforce were estimated using Gini coefficient and Lorenz curve and linear
      regression was used to determine the relation between health personnel density
      and selected health outcomes. Alternative indicators to determine health care
      needs were illustrated using concentration curves. RESULTS: Significant
      geographic inequalities in the availability of health workforce exist in
      Cameroon. Some regions have a higher number of physicians (per person) than
      others leading to poor health outcomes across the regions. 70 % of regions have a
      density of health personnel-to-population per 1,000 that is less than 1.5,
      implying acute shortage of health personnel. Poor working and living conditions,
      coupled with limited opportunities for career progress accounted for some
      documented 232 physicians and 205 nurses that migrated from the public sector.
      Significant distributional inequality was noticed when under-five infant
      mortality and malaria prevalence rate were used as indicators to measure health
      care needs. CONCLUSION: Our results show an absolute shortage of public health
      personnel in Cameroon that is further complicated by the geographic
      distributional inequalities across the regions of the nation. Cameroon aims to
      achieve universal health coverage by 2035; to realize this objective, policies
      targeting training, recruitment, retention and effective deployment of motivated
      and supported health workforce as well as the development and improvement of
      health infrastructures remain the major challenge.

PMID- 25962782
TI  - Decreased microRNA miR-181c expression in peripheral blood mononuclear cells
      correlates with elevated serum levels of IL-7 and IL-17 in patients with
      myasthenia gravis.
AB  - miR-181c is a newly identified negative regulator of immune cell activation. In
      this study, we aimed to investigate the expression and functional role of miR
      181c in myasthenia gravis (MG). miR-181c showed significant downregulation in
      peripheral blood mononuclear cells (PBMCs) from MG patients compared with healthy
      controls, with lower expression in generalized patients than in ocular ones. MG
      patients also had increased serum IL-7 and IL-17 levels. Additionally, serum IL-7
      level presents a positive correlation with the serum IL-17 level. miR-181c levels
      were negatively correlated with serum levels of IL-7 and IL-17 in either
      generalized patients or ocular patients. A luciferase reporter assay revealed
      that miR-181c could directly bind to the 3'-UTR of interleukin-7. Forced
      expression of miR-181c led to decreased IL-7 and IL-17 release in cultured PBMCs,
      while depletion of miR-181c increased the secretion of these two proinflammatory
      cytokines. The results from our study suggested for the first time that miR-181c
      was able to negatively regulate the production of proinflammatory cytokines IL-7
      and IL-17 in MG patients, and it is a novel potential therapeutic target for MG. 

PMID- 25962783
TI  - Young Australians with moderate to severe mental health problems: client data and
      outcomes at Children and Young People's Mental Health.
AB  - AIM: Almost a quarter of young Australians experience a mental health issue that
      may become chronic if left untreated. Children and Young People's Mental Health
      (CYPMH) is a specialist tertiary service for young people with moderate to severe
      mental health problems on the Central Coast in Australia. This paper presents an
      overview of client data and service use collected over a 1 year period specific
      to the Youth Mental Health (YMH) component of the service. METHOD: Client data,
      including demographic characteristics, service usage, presenting issues and
      standardized outcome measures, were analysed using SPSS. Clinicians routinely
      collect MH-OAT (Mental Health Outcomes and Assessment Tools) measures at
      different points in a client's episode of care, and each of these measures was
      analysed separately. Wilcoxon Z and a series of McNemar's tests were used to
      report on the difference between admission and discharge scores. RESULTS: During
      a designated 1 year period, 830 referrals to YMH were received. The most
      prevalent presenting issue was suicidal ideation followed by deliberate self-harm
      and depression. A comparison of admission and discharge outcome scores shows
      significant improvement by discharge on a range of measures. Specifically,
      analysis identified significant differences between admission and discharge
      HoNOSCA (Health of the Nation Outcomes Scales for Children and Adolescents) and
      CGAS (Children's Global Assessment Scale) scores for young people aged 12-17 and
      HONOS (Health of the Nation Outcomes Scale) scores for young people aged 18-24.
      CONCLUSION: The clinical outcomes for young people are positive with improvements
      seen on a range of measures.

PMID- 25962784
TI  - New approaches to reduce radiation exposure.
AB  - Exposure to ionizing radiation is associated with a long-term risk of health
      effects, including cancer. Radiation exposure to the U.S. population from cardiac
      imaging has increased markedly over the past three decades. Initiatives to reduce
      radiation exposure have focused on the tenets of appropriate study
      "justification" and "optimization" of imaging protocols. This article reviews
      ways to optimally reduce radiation dose across the spectrum of cardiac imaging. 

PMID- 25962785
TI  - Chronicles of the end of the femoral-only era and the rise of radial access in
      the modern era of tailored vascular approaches in the catheterization laboratory.

PMID- 25962786
TI  - Anammox Planctomycetes have a peptidoglycan cell wall.
AB  - Planctomycetes are intriguing microorganisms that apparently lack peptidoglycan,
      a structure that controls the shape and integrity of almost all bacterial cells.
      Therefore, the planctomycetal cell envelope is considered exceptional and their
      cell plan uniquely compartmentalized. Anaerobic ammonium-oxidizing (anammox)
      Planctomycetes play a key role in the global nitrogen cycle by releasing fixed
      nitrogen back to the atmosphere as N2. Here using a complementary array of state
      of-the-art techniques including continuous culturing, cryo-transmission electron
      microscopy, peptidoglycan-specific probes and muropeptide analysis, we show that
      the anammox bacterium Kuenenia stuttgartiensis contains peptidoglycan. On the
      basis of the thickness, composition and location of peptidoglycan in K.
      stuttgartiensis, we propose to redefine Planctomycetes as Gram-negative bacteria.
      Our results demonstrate that Planctomycetes are not an exception to the universal
      presence of peptidoglycan in bacteria. 

PMID- 25962787
TI  - Ibudilast reverses the decrease in the synaptic signaling protein
      phosphatidylethanolamine-binding protein 1 (PEBP1) produced by chronic
      methamphetamine intake in rats.
AB  - BACKGROUND: Chronic methamphetamine intake has been shown to induce a
      neuroinflammatory state leading to significant changes in brain functioning
      including behavioral changes. These changes can persist for years after drug use
      is discontinued and likely contribute to the risk of relapse. A better
      understanding of inflammation responses associated with methamphetamine intake
      may help in designing novel and more efficacious treatment strategies. METHODS:
      Rats were trained to self-administer methamphetamine or saline on a variable
      ratio 3 schedule of reinforcement (25 days). This training was followed by 12
      days of extinction (i.e., methamphetamine unavailable) during which rats received
      daily post-session administration of ibudilast (AV411; 2.5 or 7.5mg/kg) or
      saline. Following extinction, synaptosomes were isolated from the prefrontal
      cortex (PFC) and the differential pattern of synaptic proteins was assessed using
      mass spectrometry based proteomics. RESULTS: Treatment with ibudilast allowed for
      deeper extinction of active lever pressing. Quantitative mass spectrometry based
      proteomics on the PFC identified one potential hit; the synaptic signaling
      protein phosphatidylethanolamine-binding protein 1 (PEBP1). While methamphetamine
      intake was associated with reduced PEBP1 protein levels, treatment with ibudilast
      reversed this effect. Furthermore, decreased PEBP1 expression was correlated with
      subsequent activation of Raf-1, MEK, and ERK signaling components of the mitogen
      activated protein kinase cascade (MAPK). Raf-1, MEK, and ERK expression levels
      were also attenuated by ibudilast treatment. CONCLUSION: PEBP1, given its
      synaptic localization and its role as a signaling molecule acting via the
      ERK/MAPK pathway, could be a potential therapeutic target mediating drug-seeking
      behaviors associated with neuroinflammation.

PMID- 25962788
TI  - Therapist-client relationships in a psychological therapy trial for psychosis and
      substance misuse.
AB  - BACKGROUND: This study aimed to explore factors associated with outcomes in a
      randomised controlled trial of integrated motivational interviewing and cognitive
      behavioural therapy for psychosis and substance misuse. METHOD: Clients and
      therapists completed self-report measures of alliance and clients completed a
      self-report measure of adult attachment. Trial therapists were also asked to
      identify challenges in therapy, client strengths and reasons for client making
      and not making changes in relation to substance misuse. RESULTS: Neither
      therapist-rated nor client-rated alliance was significantly related to objective
      outcomes. Client insecure attachment avoidance was associated with poorer
      symptoms and functioning at 12 and 24 months; although not changes in substance
      misuse. Therapists' perceptions of therapeutic processes (e.g., challenges to
      therapy, client strengths, client reasons for change and alliance) were
      consistent with previous literature. Therapists' perceptions of client
      improvement were associated with reductions in substance use at the end of
      treatment and their ratings of therapeutic alliance. CONCLUSION: Insecure adult
      attachment styles may be a potentially important predictor of symptom outcomes
      for people with psychosis and substance misuse. Trial therapists may also provide
      an important source of information about therapeutic processes and factors
      associated with outcome.

PMID- 25962790
TI  - Large-scale monoclonal antibody purification by continuous chromatography, from
      process design to scale-up.
AB  - The development and optimization of a purification process of monoclonal
      antibodies based on two continuous chromatography steps for capture and
      intermediate purification are presented. The two chromatography steps were
      individually optimized using either batch chromatography or sequential
      multicolumn chromatography (SMCC). Proprietary simulation software was used to
      optimize SMCC and to evaluate the potential gains compared with batch
      chromatography. The SMCC recipes provided by the simulation software were
      evaluated experimentally. A good correlation was found between the simulated
      results and experimental observations. Significant gains were observed on the
      productivity, buffer consumption and the volume of resin required for SMCC over
      batch chromatography. Based on these results, a chained process from the capture
      to polishing steps was implemented. This chained process demonstrated
      significantly better performance compared with the batch equivalent while
      satisfying the specifications. The expected positive impact provided by
      implementing continuous chromatography is also discussed. 

PMID- 25962789
TI  - Daily co-occurrence of alcohol use and high-risk sexual behavior among
      heterosexual, heavy drinking emergency department patients.
AB  - BACKGROUND: Global association and experimental studies suggest that alcohol use
      may increase sexual behavior that poses risk for exposure to sexually transmitted
      infections (STI) among heterosexual men and women. However, results from
      longitudinal and daily recall studies exploring the co-occurrence of alcohol use
      with various sexual risk outcomes in more naturalistic contexts have been mixed,
      and the bulk of this research has focused on college students. METHODS: The
      current study enrolled heavy-drinking emergency department (ED) patients and used
      a cross-sectional, 30-day Timeline Followback (TLFB) method to examine the daily
      co-occurrence between alcohol use and three sexual behavior outcomes: Any sex,
      unprotected intercourse (UI), and UI with casual partners (versus protected
      intercourse [PI] with casual partners, or UI/PI with steady partners). RESULTS:
      Results indicated that increasing levels of alcohol use on a given day increased
      the odds of engaging in any sexual activity and that heavy drinking (but not very
      heavy drinking) on a given day was associated with an increased odds of engaging
      in UI with either steady or casual partners. However, day-level alcohol use was
      not associated with an increased odds of UI with casual partners. CONCLUSIONS:
      These findings suggest that alcohol may play an important role in increasing risk
      for HIV/STIs among heterosexuals, and support the continued need to target heavy
      drinking in sex risk reduction interventions. However, our results also suggest
      that alcohol may not universally result in unprotected sex with casual partners,
      a behavior posing perhaps the highest risk for HIV/STI transmission.

PMID- 25962791
TI  - Effect of bisphosphonates in preventing femoral periprosthetic bone resorption
      after primary cementless total hip arthroplasty: a meta-analysis.
AB  - BACKGROUND: Bone loss leading to aseptic loosening of the prosthesis and
      periprosthetic fracture is a mode of failure in cementless total hip arthroplasty
      (THA). The aim of this meta-analysis was to evaluate the effect of
      bisphosphonates in preventing femoral periprosthetic bone resorption following
      primary cementless THA zone by zone. METHOD: Clinical randomized controlled
      trials concerning bisphosphonates application after primary cementless THA
      published up to October 2014 were retrieved from PubMed, Cochrane library, and
      Embase databases. The methodological quality of the included studies was assessed
      by the Physiotherapy Evidence Database (PEDro) scale. Data analysis was performed
      using StataSE12.0. RESULTS: Ten randomized controlled trials involving a total of
      502 patients were assessed; the bisphosphonates group included 256 patients and
      the control group included 246 patients. The meta-analysis showed that the bone
      mineral density (BMD) of most femoral periprosthetic zones in bisphosphonates
      group was significantly higher than that in the control group at 3 months
      postoperatively except zone 5 with no significant difference. At 6 and 12 months,
      the BMD of bisphosphonates group was much higher than that in control group
      except zone 5, which showed no statistical difference. The BMD of bisphosphonates
      group was persistently higher than control group in zone 6 and 7 at 5 years
      postoperatively, while the other zones had no significant difference. Both serum
      bone alkaline phosphatase and urinary type I collagen N-telopeptide were
      significantly suppressed by bisphosphonates at 3, 6, and 12 months. CONCLUSION:
      Bisphosphonates seem to decrease early femoral periprosthetic bone resorption
      after primary cementless THA. Drug efficacy was found to be long-standing in the
      main load-bearing zones.

PMID- 25962792
TI  - IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation
      and little difference in survival: a grading problem for WHO.
AB  - The WHO 2007 classification of tumors of the CNS distinguishes between diffuse
      astrocytoma WHO grade II (A II(WHO2007)) and anaplastic astrocytoma WHO grade III
      (AA III(WHO2007)). Patients with A II(WHO2007) are significantly younger and
      survive significantly longer than those with AA III(WHO2007). So far,
      classification and grading relies on morphological grounds only and does not yet
      take into account IDH status, a molecular marker of prognostic relevance. We here
      demonstrate that WHO 2007 grading performs poorly in predicting prognosis when
      applied to astrocytoma carrying IDH mutations. Three independent series including
      a total of 1360 adult diffuse astrocytic gliomas with IDH mutation containing 683
      A II(IDHmut), 562 AA III(IDHmut) and 115 GBM(IDHmut) have been examined for age
      distribution and survival. In all three series patients with A II(IDHmut )and AA
      III(IDHmut) were of identical age at presentation of disease (36-37 years) and
      the difference in survival between grades was much less (10.9 years for A
      II(IDHmut), 9.3 years for AA III(IDHmut)) than that reported for A II(WHO2007)
      versus AA III(WHO2007). Our analyses imply that the differences in age and
      survival between A II(WHO2007) and AA III(WHO2007) predominantly depend on the
      fraction of IDH-non-mutant astrocytomas in the cohort. This data poses a
      substantial challenge for the current practice of astrocytoma grading and risk
      stratification and is likely to have far-reaching consequences on the management
      of patients with IDH-mutant astrocytoma.

PMID- 25962794
TI  - Pathology, molecular mechanisms and markers of gliomas: new insight and new
      challenges.

PMID- 25962793
TI  - Atypical multiple system atrophy is a new subtype of frontotemporal lobar
      degeneration: frontotemporal lobar degeneration associated with alpha-synuclein.
AB  - Multiple system atrophy (MSA) is a sporadic neurodegenerative disease clinically
      characterized by cerebellar signs, parkinsonism, and autonomic dysfunction.
      Pathologically, MSA is an alpha-synucleinopathy affecting striatonigral and
      olivopontocerebellar systems, while neocortical and limbic involvement is usually
      minimal. In this study, we describe four patients with atypical MSA with clinical
      features consistent with frontotemporal dementia (FTD), including two with
      corticobasal syndrome, one with progressive non-fluent aphasia, and one with
      behavioral variant FTD. None had autonomic dysfunction. All had frontotemporal
      atrophy and severe limbic alpha-synuclein neuronal pathology. The neuronal
      inclusions were heterogeneous, but included Pick body-like inclusions. The latter
      were strongly associated with neuronal loss in the hippocampus and amygdala.
      Unlike typical Pick bodies, the neuronal inclusions were positive on Gallyas
      silver stain and negative on tau immunohistochemistry. In comparison to 34
      typical MSA cases, atypical MSA had significantly more neuronal inclusions in
      anteromedial temporal lobe and limbic structures. While uncommon, our findings
      suggest that MSA may present clinically and pathologically as a frontotemporal
      lobar degeneration (FTLD). We suggest that this may represent a novel subtype of
      FTLD associated with alpha-synuclein (FTLD-synuclein). 

PMID- 25962796
TI  - A review of blood diseases and cytopenias associated with human parvovirus B19
      infection.
AB  - Parvovirus B19 is a single-stranded DNA virus which preferentially targets the
      erythroblast resulting in red cell aplasia, which is temporary in immunocompetent
      persons. Since the discovery of B19 virus in 1975, a wide variety of blood
      diseases and cytopenias affecting several blood cell lineages have been
      documented during or following B19 infection. These include cytopenias affecting
      the erythroid, megakaryoblastoid, myeloid and lymphoid lineages, as well as a
      variety of bicytopenias, pancytopenia, bone marrow necrosis / fat embolism
      syndrome, myelodysplastic syndrome, leucoerythroblastopenia, and hemophagocytic
      lymphohistiocytosis. B19 infection may also complicate and precede the course of
      acute leukemia, the significance of which remains to be determined. This review
      describes the current state of knowledge of the abnormalities of individual blood
      cell lineages encountered during parvovirus B19 infection, over the almost 40
      years since its discovery, and reveals some very interesting themes, which
      improve our understanding of the pathogenesis of B19 infection with particular
      reference to the bone marrow.

PMID- 25962795
TI  - Prolonged survival of a patient with metastatic leptomeningeal melanoma treated
      with BRAF inhibition-based therapy: a case report.
AB  - BACKGROUND: Leptomeningeal metastasis of melanoma is a devastating complication
      with a grave prognosis, and there are no known effective standard treatments.
      Although selective BRAF inhibitors have demonstrated a significant clinical
      activity in patients with metastatic melanoma harboring a BRAF mutation, the
      clinical benefit of BRAF inhibitor-based therapy in leptomeningeal disease is not
      clear. CASE PRESENTATION: We present a case of prolonged survival of a patient
      with BRAF V600E-mutant leptomeningeal disease who was treated with vemurafenib
      followed by whole brain radiation and a combination of dabrafenib and trametinib.
      Both vemurafenib and the sequential treatment of radiation and
      dabrafenib/trametinib led to regression of the leptomeningeal disease, and the
      patient survived for 19 months after the diagnosis of the leptomeningeal disease.
      CONCLUSION: This case suggests a possible clinically meaningful benefit of BRAF
      inhibitor-based therapy and a need for close investigation of this therapeutic
      approach in patients with this devastating disease.

PMID- 25962797
TI  - Massive mucinous neoplasm of the appendix.

PMID- 25962798
TI  - Diabetes, trekking and high altitude: recognizing and preparing for the risks.
AB  - Although regular physical activity is encouraged for individuals with diabetes,
      exercise at high altitude increases risk for a number of potential complications.
      This review highlights our current understanding of the key physiological and
      clinical issues that accompany high-altitude travel and proposes basic clinical
      strategies to help overcome obstacles faced by trekkers with Type 1 or Type 2
      diabetes. Although individuals with diabetes have adaptations to the hypoxia of
      high altitude (increased ventilation, heart rate, blood pressure and hormonal
      responses), elevated counter-regulatory hormones can impair glycaemic control,
      particularly if mountain sickness occurs. Moreover, high-altitude-induced
      anorexia and increased energy expenditure can predispose individuals to
      dysglycaemia unless careful adjustments in medication are performed. Frequent
      blood glucose monitoring is imperative, and results must be interpreted with
      caution because capillary blood glucose meter results may be less accurate at
      high elevations and low temperatures. It is also important to undergo pre-travel
      screening to rule out possible contraindications owing to chronic diabetes
      complications and make well-informed decisions about risks. Despite the risks,
      healthy, physically fit and well-prepared individuals with Type 1 or Type 2
      diabetes who are capable of advanced self-management can be encouraged to
      participate in these activities and attain their summit goals. Moreover, trekking
      at high altitude can serve as an effective means to engage in physical activity
      and to increase confidence with fundamental diabetes self-management skills.

PMID- 25962799
TI  - Do Birds Avoid Railroads as Has Been Found for Roads?
AB  - The construction of railway lines usually has a negative effect on the natural
      environment: habitats are destroyed, collisions with trains cause deaths, and the
      noise and vibrations associated with rail traffic disturb the lives of animals.
      Cases are known, however, where the opposite holds true: a railway line has a
      positive effect on the fauna in its vicinity. In this study, we attempted to
      define the influence of a busy railway line on a breeding community of woodland
      birds. Birds were counted using the point method at 45 observation points located
      at three different distances (30, 280, 530 m) from the tracks. At each point, we
      determined the habitat parameters and the intensity of noise. In total, 791
      individual birds of 42 species were recorded on the study plot. Even though the
      noise level fell distinctly with increasing distance from the tracks, the
      abundance of birds and the number of species were the highest near the railway
      line. Moreover, insectivorous species displayed a clear preference for the
      vicinity of the line. The noise from the trains did not adversely affect the
      birds on the study plot. The environmental conditions created by the edge effect
      meant that the birds preferred the neighborhood of the tracks: the more diverse
      habitats near the tracks supplied attractive nesting and foraging niches for many
      species of birds. Trains passing at clear intervals acted as point sources of
      noise and did not elicit any negative reactions on the part of the birds; this
      stands in contrast to busy roads, where the almost continuous flow of traffic in
      practice constitutes a linear source of noise.

PMID- 25962800
TI  - Developing Custom Fire Behavior Fuel Models for Mediterranean Wildland-Urban
      Interfaces in Southern Italy.
AB  - The dramatic increase of fire hazard in wildland-urban interfaces (WUIs) has
      required more detailed fuel management programs to preserve ecosystem functions
      and human settlements. Designing effective fuel treatment strategies allows to
      achieve goals such as resilient landscapes, fire-adapted communities, and
      ecosystem response. Therefore, obtaining background information on forest fuel
      parameters and fuel accumulation patterns has become an important first step in
      planning fuel management interventions. Site-specific fuel inventory data enhance
      the accuracy of fuel management planning and help forest managers in fuel
      management decision-making. We have customized four fuel models for WUIs in
      southern Italy, starting from forest classes of land-cover use and adopting a
      hierarchical clustering approach. Furthermore, we provide a prediction of the
      potential fire behavior of our customized fuel models using FlamMap 5 under
      different weather conditions. The results suggest that fuel model IIIP
      (Mediterranean maquis) has the most severe fire potential for the 95th percentile
      weather conditions and the least severe potential fire behavior for the 85th
      percentile weather conditions. This study shows that it is possible to create
      customized fuel models directly from fuel inventory data. This achievement has
      broad implications for land managers, particularly forest managers of the
      Mediterranean landscape, an ecosystem that is susceptible not only to wildfires
      but also to the increasing human population and man-made infrastructures. 

PMID- 25962801
TI  - Importance of nonpulmonary vein foci in catheter ablation for paroxysmal atrial
      fibrillation.
AB  - BACKGROUND: Pulmonary vein (PV) isolation is an established treatment strategy
      for paroxysmal atrial fibrillation (PAF). However, the recurrence rate of PAF is
      8% to 37%, despite repeated procedures, and the catheter ablation strategy for
      PAF with non-PV foci is unclear. OBJECTIVE: The purpose of this study was to
      assess the PAF ablation strategy for non-PV foci. METHODS: The study included 304
      consecutive patients undergoing PAF ablation (209 males, age 63.0 +/- 10.4 years)
      divided into 3 groups: group 1 (245 patients) with no inducible non-PV foci;
      group 2 (34 patients) with atrial fibrillation (AF) originating from non-PV foci
      and all the foci successfully ablated; and group 3 (25 patients) with AF
      originating from non-PV triggers, but without all foci being ablated or with
      persistently inducible AF. RESULTS: Mean follow-up period was 26.9 +/- 11.8
      months, and AF recurrence rates since the last procedure were 9.8%, 8.8%, and
      68.0% in groups 1, 2, and 3, respectively. There was no statistically significant
      difference in recurrence rate between groups 1 and 2 (P = .89); however, there
      were statistically significant differences between groups 3 and 1 (P <.0001) and
      groups 3 and 2 (P <.0001). The patients in group 2 had an AF-free outcome to
      equivalent to those who had PV foci in group 1 (P = .83). CONCLUSION: Success
      rates can be improved for PAF ablation if non-PV foci are detected and
      eliminated.

PMID- 25962802
TI  - Temporal-component analysis of diastolic electrograms in ventricular tachycardia
      differentiates nonvulnerable regions of the circuit.
AB  - BACKGROUND: Successful activation mapping of ventricular tachycardia (VT) is
      dependent on the identification of a region of diastolic conduction by use of
      point-by-point sequential mapping. It is important to identify the site of
      transition from diastolic conduction to systolic activation of healthy myocardium
      (exit site) and differentiate this from nonvulnerable regions of the circuit.
      OBJECTIVE: We sought to determine the temporal and component characteristics of
      exit-site electrograms using simultaneous multielectrode endocardial mapping and
      to differentiate them from bystander sites during activation mapping. METHODS:
      Sixteen VTs induced in 12 patients with ischemic cardiomyopathy who underwent
      multielectrode mapping during VT performed with a custom-made 112-bipolar
      electrode endocardial array were analyzed retrospectively. The activation
      sequence in systole and diastole was annotated, and the timing at exit and
      bystander sites of the near-field component was characterized in relation to
      surface electrocardiogram activation and to the far-field component. Spectral
      content of bipolar electrograms recorded at these sites was additionally analyzed
      to identify the near-field to far-field interval. RESULTS: The mean activation
      time at exit sites was 60.0 +/- 31.5 ms (range 21-113 ms) ahead of surface QRS
      but was not significantly different from bystander sites (72.0 +/- 55.0 ms, P =
      .63). However, the time delay from local to far-field activity was significantly
      lower at exit sites than at bystander sites (24.9 +/- 15.6 vs. 86.6 +/- 92.0 ms,
      P = .003), which was confirmed by spectral analysis (10.0 +/- 13.1 vs. 89.0 +/-
      64.5 ms, P = .003). CONCLUSION: Our analysis suggests that temporal-component
      analysis of diastolic electrograms during activation mapping of VT provides a
      practical method to differentiate nonvulnerable sites from the exit site without
      the need for pacing maneuvers.

PMID- 25962803
TI  - Same-day cardiac catheter ablation is safe and cost-effective: Experience from a
      UK tertiary center.
AB  - BACKGROUND: Catheter ablation is a curative intervention for common arrhythmias
      such as supraventricular tachycardia and atrial flutter. Many centers still admit
      patients overnight after this procedure. OBJECTIVE: This study was performed to
      evaluate the safety and cost-effectiveness of same-day standard catheter
      ablation. METHODS: We conducted a retrospective study of all consecutive elective
      same-day procedures performed between 2010 and 2014. Data were collected on
      baseline parameters, procedure details and success, postoperative complications,
      unplanned overnight hospital admissions, and clinical outcome (including
      mortality) at 4-month follow-up. A cost analysis of potential savings was also
      performed. RESULTS: A total of 1142 patients underwent planned same-day
      electrophysiological study with or without ablation. Radiofrequency ablation was
      performed in 897 of these patients (mean age +/- standard error 56 +/- 0.6 years,
      range 16-95 years, 467 males), with 921 arrhythmias ablated and with complete
      procedural success in 883 cases (96%). There were 92 unplanned admissions
      (10.3%): 50 for concealed pathways that required transseptal puncture, 19 for
      immediate complications (including 9 femoral bleeds and 5 pacemakers for heart
      block), 12 admitted at the operator's discretion, and 11 for other clinical
      reasons. All had transthoracic echocardiography after the procedure, and none had
      significant pericardial effusion. At 4-month follow-up, there were 16
      readmissions (1 deep vein thrombosis, 3 pericarditic chest pain, 2 femoral
      hematomas, 7 palpitations, and 3 others) and 1 death (unrelated to ablation). An
      overnight stay at our center costs $450 (L300); same-day ablation over this
      period saved our institution $365,000 (L240,000). CONCLUSION: Same-day standard
      catheter ablation is safe and cost-effective, with significant benefits for
      patients and health care providers. This is particularly important given the
      current financial climate.

PMID- 25962804
TI  - Risk assessment for atrial fibrillation: Enter the P-wave.

PMID- 25962805
TI  - Borrelia miyamotoi is widespread in Ixodes ricinus ticks in southern Norway.
AB  - From April to October 2007, host-seeking Ixodes ricinus ticks were collected from
      four locations in southern Norway; Farsund, Mandal, Sogne and Tromoy,
      respectively. Larvae (n=210), nymphs (n=1130) and adults (n=449) were
      investigated for infection with Borrelia miyamotoi by real-time polymerase chain
      reaction (PCR) amplification of part of the 16S rRNA gene. Results were verified
      by direct sequencing of the PCR amplicon generated from the rrs (16S)-rrl (23S)
      intergenetic spacer. B. miyamotoi was detected at all sites and throughout the
      period of questing activity, with infection prevalence (<=1.26%) similar to what
      has been seen in other European countries. Detection of the relapsing fever
      spirochete at all locations indicates a wide distribution in southern Norway.
      This is the first report of B. miyamotoi prevalence in ticks collected from
      Norway. As not much is known about the spatiotemporal dynamics of this relatively
      recently discovered pathogen, the conclusions of this study significantly add to
      the knowledge regarding B. miyamotoi in this region. 

PMID- 25962806
TI  - Treatment of distal biceps tendon rupture: why, when, how? Analysis of literature
      and our experience.
AB  - INTRODUCTION: The rupture of the distal biceps tendon is a relatively uncommon
      lesion. Even if conservative treatment may be an option in low demanding
      patients, young and active subjects may benefit from an early surgical
      reinsertion. Many techniques and fixation devices have been described, but in the
      literature, there are no clinical evidences that show the superiority of any of
      these. In this article, we report an analysis of the "state of the art" and our
      case series of surgical reinsertion with the double approach transosseous
      technique. MATERIALS AND METHODS: Between 2003 and 2013, 26 patients underwent
      surgical reinsertion, either for acute or for chronic lesions of distal biceps
      tendon. We evaluated 21 acute cases treated with double approach using DASH and
      SECEC Elbow Scores. The mean follow-up was 22 months. Range of motion, supination
      and flexion strength were also recorded. RESULTS: Mean final ROM was 6-132
      degrees  in F/E and 89-0-87 degrees  in P/S; flexion and supination strength were
      96 and 88 % compared to the opposite side. The main complications were two cases
      of heterotopic ossifications: one asymptomatic fracture of the proximal radius
      and one temporary neurapraxia of the radial nerve. CONCLUSIONS: Analysing the
      literature and our outcomes, we underline the importance of timing for surgery,
      in young and compliant patients, with a valid rehabilitation protocol for
      excellent results. The choice of surgical technique remains controversial, and we
      believe that the double approach transosseous reinsertion is a safe, costless and
      relatively non-invasive technique, offering satisfactory results when performed
      early.

PMID- 25962807
TI  - Reverse shoulder prosthesis to treat complex proximal humeral fractures in the
      elderly patients: results after 10-year experience.
AB  - PURPOSE: The aim of this study is to report the clinical and radiological results
      of reverse total shoulder arthroplasty (rTSA) in elderly patients who have been
      treated for complex humeral fractures. MATERIALS AND METHODS: From January 2005
      to December 2014, we have implanted rTSA for proximal humeral fractures in 95
      patients (80 women, 15 men) about 75 years old on average (range 62-95 years).
      All rates and results on intraoperative and postoperative complications have been
      collected in a specific database. In all cases we have used a modular implant
      prosthesis (Lima Corporate, San Daniele del Friuli, Italy). The prosthesis was
      implanted cementless in 92 cases. Because of the presence of a high percentage of
      comorbidities in the elderly patients, we have retrospectively analyzed the
      necessity of a secondary hospitalization, from a week to a 6-month time after the
      discharge, due to general health problems and specific postoperative shoulder
      complications. The mean follow-up was 5 years (range 1-9 years) for 70 of 95
      patients, 50 of whom had adequate radiographic controls. RESULTS: None of 95
      patients has required a reoperation or a hospitalization for general health
      problems from 1 week to 6 months postoperative. No early or late infection of
      prosthesis has been observed. There were seven cases of perioperative
      complications, three humeral vertical bone fissuring, two glenoid fractures and
      two cases of deltoid muscle damage. We have had three cases of postoperative
      hematoma and one case of ulnar nerve neuropathy. The mean constant score was
      85.4, and the mean simple shoulder test was 7.4. We have observed a grade 1
      scapular notching in 15 cases (30 %). In the remaining 35 reviewed cases, there
      was no notching. Peri-articular heterotopic ossifications were found in 11 cases
      (22 %). CONCLUSION: Reverse shoulder prosthesis in complex humeral fractures in
      the elderly can be considered as a reliable surgical procedure, which leads to
      very good clinical and radiological results in case of cementless prosthesis, as
      well.

PMID- 25962808
TI  - Proximal humeral fracture fixation: multicenter study with carbon fiber peek
      plate.
AB  - BACKGROUND: Locking plate fixation is a reliable treatment for many displaced
      proximal humeral fractures. Carbon fiber-reinforced-poly-ether-ether-ketone (CFR
      PEEK) plates have recently been introduced as an alternative to traditional
      metallic plates. METHODS: In a multicenter study involving the Orthopedic
      Services of 6 Italian hospitals, 182 patients with a proximal humeral fracture
      were treated with a Diphos H (Lima Corporate, San Daniele del Friuli, Italy) CFR
      PEEK plate, 160 of whom were followed clinically and radiographically for 2 years
      or more. Fractures were classified by Neer's system. The functional results were
      assessed by Constant and DASH scores. RESULTS: The average time to radiographic
      healing was 5.6 months in 158 of 160 cases. Mean Constant score was 76, and mean
      DASH score was 28 at 2 years. There were two nonunions (one septic and one
      aseptic) and 13 cases of partial (9) or massive (4) humeral head necrosis. In
      three of the 78 patients treated with the first-generation plates, hardware
      breakage happened during the operation and the plate was replaced. There was no
      failure among the cases treated with the thicker second-generation plate. In
      eight cases, there was a perforation of the humeral head by the cephalic screws.
      CONCLUSIONS: CFR-PEEK plates proved as reliable as metallic plates in the
      treatment of proximal humeral fractures. The advantages of these new devices
      include a better visualization of fracture reduction during intraoperative
      fluoroscopic assessment and easy hardware removal due to the absence of screw
      plate cold fusion.

PMID- 25962809
TI  - Non-thermal extremely low frequency magnetic field effects on opioid related
      behaviors: Snails to humans, mechanisms to therapy.
AB  - In 1984, it was initially discovered in mice that an extremely low frequency
      magnetic field (ELF-MF) could attenuate opiate induced analgesia. In the past 30
      years, we defined some of ELF-MF exposure and subject state conditions that can
      both increase and decrease nociception in snails and mice and can induce
      analgesia in humans. In our search for mechanisms and our desire to translate our
      findings to the treatment of chronic pain in humans, we pioneered the use of
      electroencephalography and magnetic resonance imaging to monitor effects during
      exposure. We have contributed to an understanding of the phenomena but a
      considerable amount remains to be done by us and those who have undertaken
      corroboratory and complimentary work. As the recipient of the 2013 d'Arsonval
      Award, I was invited to prepare an article for Bioelectromagnetics that
      highlights research findings that led to the award. Here, I have focused on our
      main findings associated with the effects of nociception of exposure to ELF-MF.
      To enrich the value of this contribution, I have put our research into the
      context of work of others. Further, I have suggested future directions of
      research and the potential for linkages and synergies associated with the
      extensive literature on animal orientation. Hence, it needs to be acknowledged
      that this is a report of our contributions and not intended as a balanced review.

PMID- 25962810
TI  - A meta-analysis of the association between IL28B polymorphisms and infection
      susceptibility of hepatitis B virus in Asian population.
AB  - BACKGROUND: Several association studies with small sample sizes of two SNPs in
      IL28BB (rs12979860 and rs8099917) showed inconsistent results, so in this study,
      we aim to evaluate the association between the two SNPs and infection
      susceptibility of Hepatitis B Virus (HBV) in Asian population, especially in
      Chinese population by meta-analysis. METHODS: Search the relevant published
      papers and perform meta-analysis respectively on IL28B (rs12979860 and rs8099917)
      in Asian population and Chinese population under an additive genetic model by
      STATA11.0. RESULTS: The pooled odds ratios (OR) of rs12979860 are 0.79 (95% CI,
      0.53-1.18; P = 0.25, I(2) = 63.2%) and 1.62 (95% CI, 1.04-2.51; P = 0.033, I(2) =
      54.3%) respectively in Asian population and Chinese population analysis. The
      pooled OR of rs8099917 are 1.05 (95% CI, 0.93-1.19; P = 0.44, I(2) = 43.3%) and
      0.97 (95% CI, 0.84-1.23; P = 0.726, I(2) = 15.6%) respectively in Asian
      population and Chinese population analysis. CONCLUSION: Our study demonstrated
      that T allele of rs12979680 can increase the risk of HBV infection in Chinese
      population but not Asian population under an additive genetic model. There is no
      association between rs8099917 and HBV infection in Chinese population and Asian
      population.

PMID- 25962813
TI  - Outcome of single level disc prolapse treated with transforaminal steroid versus
      epidural steroid versus caudal steroids.
AB  - OBJECTIVE: To determine the efficacy of fluoroscopic guided transforaminal
      steroid versus interlaminar epidural steroid versus caudal steroid. MATERIAL AND
      METHOD: A total of 90 patients were studied who had complains of low back pain
      with radiculopathy and MRI evidence of disc prolapse. Out of this group, patients
      were randomly assigned to three groups each having 30 patients. First group
      received transforaminal steroid injection, second group received caudal steroid
      injection, and third group received epidural steroid. All patients were followed
      up for 12 months, and the results were compared using change in Visual Analogue
      Scale score and Oswestry Disability Index (OSD). RESULTS: The change in pain
      scores was statistically different at 1- and 6-month interval such that a higher
      change was observed by transforaminal route as compared to the other two. There
      was no difference in change of scores between interlaminar and caudal routes. For
      OSD, a greater change was seen in transforminal at all times as compared to the
      other two. There was no difference in change of scores between interlaminar and
      caudal routes at any time of assessment. CONCLUSION: In current study,
      transforaminal steroid injection group has better symptomatic improvement for
      both short and long term as compared to interlaminar and caudal steroid injection
      group.

PMID- 25962812
TI  - Discussing sexual health in spinal care.
AB  - BACKGROUND: The possible detrimental effects of spinal disease on sexual health
      are widely recognized; however, it is not known to what extent neurosurgeons
      discuss this topic with their patients. The aim of this study is to identify
      knowledge, attitude and practice patterns of neurosurgeons counseling their
      patients about sexual health. METHODS: All members of the Dutch Association of
      Neurosurgery (neurosurgeons and residents) were sent a questionnaire addressing
      their attitudes, knowledge and practice patterns regarding discussing sexual
      health. RESULTS: Response rate was 62% with 89 questionnaires suitable for
      analysis. The majority of participants (83%) were male; mean age, 42.4 years. The
      mean experience in neurosurgical practice was 9 years. Respondents assumed that
      in 34% of their patients, sexual health was affected due to spinal disease. The
      majority of respondents (64%) stated that responsibility for discussing sexual
      health lies (partly) with the neurosurgeon; however, 73% indicated to (almost)
      never do this. The main reasons for not discussing sexual health were patients'
      old age (42%), lack of knowledge (38%) and lack of patients' initiative to bring
      up the subject (36%). Twenty-six percent indicated lack of time as a reason.
      There was no evidence for gender or doctor's age discordance as important
      barriers. Fifty percent of participants wished to gain more knowledge on
      discussing sexual health with patients. CONCLUSION: This study shows that despite
      high prevalence of sexual dysfunction (SD) in spinal patients, counseling about
      sexual health is not often done in neurosurgical care. More training on sexual
      health counseling early in the residency program seems critical. By initiating
      the discussion, clinicians who deal with spinal patients have the potential to
      detect sexual dysfunction (SD) and to refer adequately when necessary, thereby
      improving overall quality of life of their patients.

PMID- 25962811
TI  - Non-Hodgkin Lymphoma, Body Mass Index, and Cytokine Polymorphisms: A Pooled
      Analysis from the InterLymph Consortium.
AB  - BACKGROUND: Excess adiposity has been associated with lymphomagenesis, possibly
      mediated by increased cytokine production causing a chronic inflammatory state.
      The relationship between obesity, cytokine polymorphisms, and selected mature B
      cell neoplasms is reported. METHOD: Data on 4,979 cases and 4,752 controls from
      nine American/European studies from the InterLymph consortium (1988-2008) were
      pooled. For diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and
      chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), joint
      associations of body mass index (from self-reported height and weight) and 12
      polymorphisms in cytokines IL1A (rs1800587), IL1B (rs16944, rs1143627), IL1RN
      (rs454078), IL2 (rs2069762), IL6 (rs1800795, rs1800797), IL10 (rs1800890,
      rs1800896), TNF (rs1800629), LTA (rs909253), and CARD15 (rs2066847) were
      investigated using unconditional logistic regression. BMI-polymorphism
      interaction effects were estimated using the relative excess risk due to
      interaction (RERI). RESULTS: Obesity (BMI >= 30 kg/m(2)) was associated with
      DLBCL risk [OR = 1.33; 95% confidence interval (CI), 1.02-1.73], as was TNF
      308GA+AA (OR = 1.24; 95% CI, 1.07-1.44). Together, being obese and TNF-308GA+AA
      increased DLBCL risk almost 2-fold relative to those of normal weight and TNF
      308GG (OR = 1.93; 95% CI, 1.27-2.94), with a RERI of 0.41 (95% CI, -0.05-0.84;
      Pinteraction = 0.13). For FL and CLL/SLL, no associations with obesity or TNF
      308GA+AA, either singly or jointly, were observed. No evidence of interactions
      between obesity and the other polymorphisms were detected. CONCLUSIONS: Our
      results suggest that cytokine polymorphisms do not generally interact with BMI to
      increase lymphoma risk but obesity and TNF-308GA+AA may interact to increase
      DLBCL risk. IMPACT: Studies using better measures of adiposity are needed to
      further investigate the interactions between obesity and TNF-308G>A in the
      pathogenesis of lymphoma.

PMID- 25962815
TI  - Is neck tilt and shoulder imbalance the same phenomenon? A prospective analysis
      of 89 adolescent idiopathic scoliosis patients (Lenke type 1 and 2).
AB  - PURPOSE: To introduce a new clinical neck tilt grading and to investigate
      clinically and radiologically whether neck tilt and shoulder imbalance is the
      same phenomenon in AIS patients. METHODS: 89 AIS Lenke 1 and 2 cases were
      assessed prospectively using the new clinical neck tilt grading. Shoulder
      imbalance and neck tilt were correlated with coracoid height difference (CHD),
      clavicle?rib intersection distance (CRID), clavicle angle (CA), radiographic
      shoulder height (RSH), T1 tilt and cervical axis. RESULTS: Mean age was 17.2 +/-
      3.8 years old. 66.3 % were Lenke type 1 and 33.7 % were type 2 curves. Strong
      intraobserver (0.79) and interobserver (0.75) agreement of the clinical neck tilt
      grading was noted. No significant correlation was observed between clinical neck
      tilt and shoulder imbalance (0.936). 56.3 % of grade 3 neck tilt, 50.0 % grade 2
      neck tilt patients had grade 0 shoulder imbalance. In patients with grade 2
      shoulder imbalance, 42.9 % had grade 0, 35.7 % grade 1, 14.3 % grade 2 and only
      7.1 % had grade 3 neck tilt. CHD, CRID, CA and RSH correlated with shoulder
      imbalance. T1 tilt and cervical axis measurements correlated with neck tilt.
      CONCLUSIONS: In conclusion, neck tilt is distinct from shoulder imbalance.
      Clinical neck tilt has poor correlation with clinical shoulder imbalance.
      Clinical neck tilt grading correlated with cervical axis and T1 tilt whereas
      clinical shoulder grading correlated with CHD, RSH CRID and CA.

PMID- 25962814
TI  - Markers of inflammation and fibrinolysis in relation to outcome after surgery for
      lumbar disc herniation. A prospective study on 177 patients.
AB  - PURPOSE: The role of inflammation and fibrinolysis for the development of back
      pain and sciatica has been discussed. The aim of this study was to assess the
      relationship between markers of inflammation and fibrinolysis, to predict the
      outcome after surgery for lumbar disc herniation. METHODS: 177 patients were
      recruited. High sensitive C-reactive protein (hsCRP), plasminogen activator
      inhibitor 1 (PAI-1), fibrinogen, and D-dimer were analyzed preoperatively. Visual
      analogue scale (VAS) for back and leg pain, Oswestry Disability Index (ODI), and
      EuroQol 5 Dimensions (EQ-5D) were assessed preoperatively and at 6 weeks, 6-, 12
      , and 24- months postoperatively. Dichotomization was made at the median for the
      laboratory analyses, and between the worst quartile and the other three quartiles
      for the outcome variables. Logistic regression was used to determine the odds
      ratios (OR) and 95 % confidence intervals (CI). RESULTS: The associations between
      PAI-1 and outcome seemed to be most prominent at the 6 and 12-month follow-up.
      When being in the upper half of PAI-1, the OR for being in the worst quartile of
      VAS back pain 12 months postoperatively was 3.33 (1.56-7.10). The corresponding
      OR for VAS leg pain was 2.46 (1.18-5.10), for ODI 2.83 (1.35-5.94) and for EQ-5D
      2.73 (1.30-5.75). The OR for hsCRP was 2.10 (1.03-4.29) for being in the worst
      quartile of VAS back pain. Fibrinogen or D-dimer was not associated with any
      outcome variable. CONCLUSIONS: High PAI-1, a marker of fibrinolysis, was fairly
      consistently associated with poor outcome, while hsCRP, fibrinogen, and D-dimer
      were not.

PMID- 25962817
TI  - Thematic issue: Biologics in autoimmune diseases.

PMID- 25962816
TI  - Pretreatment platelet count improves the prognostic performance of the TNM
      staging system and aids in planning therapeutic regimens for nasopharyngeal
      carcinoma: a single-institutional study of 2,626 patients.
AB  - INTRODUCTION: Thrombocytosis has been identified as an unfavorable prognostic
      factor in several types of cancer. This study aimed to evaluate the prognostic
      value of pretreatment platelet count in association with the TNM staging system
      and therapeutic regimens in patients with nasopharyngeal carcinoma (NPC).
      METHODS: A total of 2,626 patients with NPC were retrospectively analyzed.
      Platelet count >300 * 10(9)/L was defined as thrombocytosis. Matched-pair
      analysis was performed between patients receiving chemoradiotherapy and
      radiotherapy. RESULTS: Multivariate analysis showed that platelet count was an
      independent unfavorable prognostic factor for overall survival (OS) [hazard ratio
      (HR) = 1.810, 95% confidence interval (CI) = 1.531-2.140, P < 0.001] and distant
      metastasis-free survival (DMFS) (HR = 1.873, 95% CI = 1.475-2.379, P < 0.001) in
      the entire patient cohort. Further subgroup analysis revealed that increased
      platelet count was an independent unfavorable prognostic factor for OS and DMFS
      in patients with NPC stratified by early and advanced T category, N category, or
      TNM classification (all P <= 0.001). Receiver operating characteristic (ROC)
      curves verified that the predictive value of TNM classification for OS was
      improved when combined with pretreatment platelet count (P = 0.030). Matched-pair
      analysis showed that chemoradiotherapy significantly improved OS only in advanced
      stage NPC with thrombocytosis (HR = 0.416, 95% CI = 0.226-0.765, P = 0.005).
      CONCLUSIONS: Pretreatment platelet count, when combined with TNM classification,
      is a useful indicator for metastasis and survival in patients with NPC. It may
      improve the predictive value of the TNM classification and help to identify
      patients likely to benefit from more aggressive therapeutic regimens.

PMID- 25962818
TI  - Rheumatoid Arthritis - Anti-TNF.
AB  - This review will focus on the recent information and strategies now informing
      best use of TNF inhibitor therapy in RA. These issues include the role of TNFi
      therapy in early RA management, anti-drug antibodies in TNFi therapy, updates on
      safety and optimal dosage regimens in long term management. 

PMID- 25962819
TI  - Effects of selenizing angelica polysaccharide and selenizing garlic
      polysaccharide on immune function of murine peritoneal macrophage.
AB  - The effects of two selenizing polysaccharides (sCAP2 and sGPS6) on immune
      function of murine peritoneal macrophages taking two non-selenizing
      polysaccharides (CAP and GPS) and modifier Na2SeO3 as control. In vitro test, the
      changes of selenizing polysaccharides, non-selenizing polysaccharides and Na2SeO3
      on murine macrophages function were evaluated by phagocytosis and nitric oxide
      (NO) secretion tests. In vivo test, the mice were injected respectively with 0.2,
      0.4 and 0.6 mg of sCAP2, sGPS6, CAP and GPS, or Na2SeO3 80 MUg or normal saline
      0.4 mL. The peritoneal macrophages were collected and cultured to determine the
      contents of TNF-alpha, IL-6 and IL-10 in supernatants by enzyme-linked
      immunosorbent assay. The results showed that sCAP2 and sGPS6 could significantly
      promote the phagocytosis and secretion of NO and three cytokines of macrophages
      in comparison with CAP and GPS. sCAP2 possessed the strongest activity. This
      indicates that selenylation modification can further improve the immune-enhancing
      activity of polysaccharide, and sCAP2 could be as a new immunopotentiator.

PMID- 25962820
TI  - Differential expression of serum microRNAs in cirrhosis that evolve into
      hepatocellular carcinoma related to hepatitis B virus.
AB  - Circulating microRNAs (miRNAs) exist stably in body fluids and are potential
      biomarkers for hepatocellular carcinoma (HCC). Twenty-five patients with
      cirrhosis that evolved into HCC, who were treated at The Third Hospital of
      Zhenjiang Affiliated to Jiangsu University between January 2005 and December
      2012, were enrolled. In the discovery stage, 2 serum samples pooled from 3
      cirrhosis and 3 HCC samples were subjected to deep sequencing. Subsequently,
      differential expression of miRNAs was validated by quantitative reverse
      transcription-polymerase chain reaction (qRT-PCR) in the serum samples from an
      independent cohort of 22 patients with cirrhosis and HCC. Twenty-two miRNAs
      showed a >2-fold upregulation (P<0.01), and 2 miRNAs showed a >2-fold
      downregulation (P<0.01) in the cirrhosis and HCC samples. Using the comparative
      Ct method, we calculated the 2-(DeltaDeltaCt) for 40 candidate miRNAs in the
      sample sets. Eight of the 40 miRNAs demonstrated significantly differential
      expression levels between the disease categories. The miRNAs exhibiting
      differential expression were hsa-miR-122-5p, has-miR-199a-5p, hsa-miR-486-5p, has
      miR-193b-5p, hsa-miR-206, has-miR-141-3p, has-miR-192-5p and has-miR-26a-5p. We
      identified the miRNAs differentially expressed in cirrhosis that evolved into
      hepatitis B virus-related HCC.

PMID- 25962821
TI  - Chronic administration of N-acetyl-D-mannosamine improves age-associated
      impairment of long-term potentiation in the senescence-accelerated mouse.
AB  - N-Acetyl-D-mannosamine (ManNAc), a precursor of a sialic acid, is recently
      reported to improve the cognitive function in aged animals. However, the effect
      of chronic administration of ManNAc on impaired synaptic transmission and
      plasticity with age still remain unknown. In this study, we
      electrophysiologically determined the effect of chronic administration of ManNAc
      on deteriorated synaptic transmission and plasticity using hippocampal slices
      from senescence-accelerated mouse prone 8 (SAMP8) which shows age-related
      impairment of learning and memory. Oral administration of ManNAc for 8 weeks
      improved the field excitatory postsynaptic potentials (fEPSPs) in both SAMP8 and
      SAM resistant 1 (SAMR1), the control strain of SAMP8, at 14 months of age, but
      not at 6 months of age. On the other hand, ManNAc administration improved long
      term potentiation (LTP), representative of long-term synaptic plasticity, of 6
      month-old SAMP8 but not of age-matched SAMR1. In addition, ManNAc improved LTP of
      14 month-old SAMR1 but not of age-matched SAMP8. At the same time, we checked the
      PPR but ManNAc did not affect the PPRs at either before or after high-frequency
      stimulation for LTP induction. These results indicate that chronic administration
      of ManNAc improves the age-dependent attenuation of synaptic transmission and
      LTP, and shows the availability of ManNAc treatment as potential therapeutic
      application for cognitive dysfunction.

PMID- 25962822
TI  - Role of actin filaments in allodynia induced by chronic compression of the dorsal
      root ganglion.
AB  - The role of actin filaments in allodynia induced by chronic compression of the
      dorsal root ganglion (DRG) (CCD) and the effects of microfilaments dynamics on
      transient receptor potential vanilloid 4 (TRPV4) were investigated in this study.
      Anti-microfilaments agents resulted in dose-dependent and partial reduction in
      CCD-induced allodynia, which could be prevented by the prior stabilizer
      administration. In association with the reduction of allodynia by microfilaments'
      disruption, TRPV4-mediated currents were inhibited by disruptors. In addition,
      plasma membrane-associated TRPV4 was also depressed by disruptors. The time
      courses for the changes of TRPV4 activity and distribution in vitro were similar
      to the time courses for the attenuation of allodynia in vivo. Phalloidin, the
      stabilizer of microfilaments, did not affect the allodynia in CCD rats. However,
      phalloidin resulted in reduction and delay of TRPV4 current, which was not
      consistent with the effect of phalloidin on CCD-induced allodynia. In accordance
      with the inhibition of TRPV4 activity, the reversal potentials shifted toward
      more positive voltages and the plasma membrane-associated TRPV4 was depressed by
      phalloidin. In conclusion, intact actin filaments were necessary for CCD-induced
      allodynia, and disruptors of microfilaments attenuated CCD-induced allodynia.
      However, stabilizer of actin filaments did not affect allodynia in CCD rats.
      Further, TRPV4 contributed to the disruptors-induced attenuation of allodynia in
      CCD rats. 

PMID- 25962823
TI  - Recruitment and retention of junior clinical teachers.

PMID- 25962824
TI  - An Improved Nonradioactive Screening Method Identifies Genistein and Xanthohumol
      as Potent Inhibitors of Iodothyronine Deiodinases.
AB  - BACKGROUND: Deiodinases (DIO1, 2, and 3) are key enzymes in thyroid hormone (TH)
      activation and inactivation with impact on energy metabolism, development, cell
      differentiation, and a number of other physiological processes. The three DIO
      isoenzymes thus constitute sensitive rate-limiting components within the TH axis,
      prone to dysregulation by endocrine disruptive compounds or disease state. In
      animal models and cell culture experiments, they serve as readout for local TH
      status and disarrangement of the hormonal axis. Furthermore, some human diseases
      are characterized by apparent deiodinase dysregulation (e.g., the low
      triiodothyronine syndrome in critical illness). Consequently, these enzymes are
      targets of interest for the development of pharmacological compounds with
      modulatory activities. Until now, the portfolio of inhibitors for these enzymes
      is limited. In the clinics, the DIO1-specific inhibitor propylthiouracil is in
      use for treatment of severe hyperthyroidism. Other well-known inhibitors (e.g.,
      iopanoic acid or aurothioglucose) are nonselective and block all three
      isoenzymes. Furthermore, DIO3 was shown to be a potential oncogenic gene, which
      is strongly expressed in some tumors and might, in consequence, protect tumor
      tissue form differentiation by TH. With respect to its role in tumorigenesis,
      specific inhibitors of DIO3 as a potential target for anticancer drugs would be
      highly desirable. To this end, a flexible and convenient assay for high
      throughput screening is needed. We recently described a nonradioactive screening
      assay, utilizing the classic Sandell-Kolthoff reaction as readout for iodide
      release from the substrate molecules. While we used murine liver as enzyme
      source, the assay was limited to murine DIO1 activity testing. Here, we describe
      the use of recombinant proteins as enzyme sources within the assay, expanding its
      suitability from murine Dio1 to human DIO1, DIO2, and DIO3. METHODS: As proof-of
      concept, deiodination reactions catalyzed by these recombinant enzymes were
      monitored with various nonradioactive substrates and confirmed by liquid
      chromatography-tandem mass spectrometry. RESULTS: The contrast agent and known
      DIO inhibitor iopanoic acid was characterized as readily accepted substrate by
      DIO2 and Dio3. In a screening approach using established endocrine disrupting
      compounds, the natural food ingredient genistein was identified as a further DIO1
      specific inhibitor, while xanthohumol turned out to potently block the activity
      of all three isoenzymes. CONCLUSIONS: A rapid nonradioactive screening method
      based on the Sandell-Kolthoff reaction is suitable for identification of
      environmental, nutritive and pharmacological compounds modulating activities of
      human deiodinase enzymes.

PMID- 25962825
TI  - Waste heat generation: A comprehensive review.
AB  - A comprehensive review of heat generation in various types of wastes and of the
      thermal regime of waste containment facilities is provided in this paper.
      Municipal solid waste (MSW), MSW incineration ash, and mining wastes were
      included in the analysis. Spatial and temporal variations of waste temperatures,
      thermal gradients, thermal properties of wastes, average temperature
      differentials, and heat generation values are provided. Heat generation was
      influenced by climatic conditions, mean annual earth temperatures, waste
      temperatures at the time of placement, cover conditions, and inherent heat
      generation potential of the specific wastes. Time to onset of heat generation
      varied between months and years, whereas timelines for overall duration of heat
      generation varied between years and decades. For MSW, measured waste temperatures
      were as high as 60-90 degrees C and as low as -6 degrees C. MSW incinerator ash
      temperatures varied between 5 and 87 degrees C. Mining waste temperatures were in
      the range of -25 to 65 degrees C. In the wastes analyzed, upward heat flow toward
      the surface was more prominent than downward heat flow toward the subsurface.
      Thermal gradients generally were higher for MSW and incinerator ash and lower for
      mining waste. Based on thermal properties, MSW had insulative qualities (low
      thermal conductivity), while mining wastes typically were relatively conductive
      (high thermal conductivity) with ash having intermediate qualities. Heat
      generation values ranged from -8.6 to 83.1MJ/m(3) and from 0.6 to 72.6MJ/m(3) for
      MSW and mining waste, respectively and was 72.6MJ/m(3) for ash waste. Conductive
      thermal losses were determined to range from 13 to 1111MJ/m(3)yr. The data and
      analysis provided in this review paper can be used in the investigation of heat
      generation and thermal regime of a wide range of wastes and waste containment
      facilities located in different climatic regions. 

PMID- 25962826
TI  - Integrating remediation and resource recovery: On the economic conditions of
      landfill mining.
AB  - This article analyzes the economic potential of integrating material separation
      and resource recovery into a landfill remediation project, and discusses the
      result and the largest impact factors. The analysis is done using a direct
      costs/revenues approach and the stochastic uncertainties are handled using Monte
      Carlo simulation. Two remediation scenarios are applied to a hypothetical
      landfill. One scenario includes only remediation, while the second scenario adds
      resource recovery to the remediation project. Moreover, the second scenario is
      divided into two cases, case A and B. In case A, the landfill tax needs to be
      paid for re-deposited material and the landfill holder does not own a combined
      heat and power plant (CHP), which leads to disposal costs in the form of gate
      fees. In case B, the landfill tax is waived on the re-deposited material and the
      landfill holder owns its own CHP. Results show that the remediation project in
      the first scenario costs about ?23/ton. Adding resource recovery as in case A
      worsens the result to -?36/ton, while for case B the result improves to -?14/ton.
      This shows the importance of landfill tax and the access to a CHP. Other
      important factors for the result are the material composition in the landfill,
      the efficiency of the separation technology used, and the price of the saleable
      material. 

PMID- 25962827
TI  - Trajectories of depressive symptoms and oral health outcomes in a community
      sample of older adults.
AB  - OBJECTIVE: Adverse outcomes associated with chronic depressive symptoms are of
      clinical importance. The objective was to identify subgroups of older adults
      based on their trajectories of depressive symptoms over a 10-year period and
      determine if these subgroups predicted oral health outcomes. METHODS: The sample
      was 944 adults aged 65+ who participated in the oral health module of the the
      Health and Retirement Survey in 2008. Depressive symptoms were measured with a
      modified version of the Center for Epidemiologic Studies-Depression (CES-D)
      scale. Latent class trajectory analysis was used to identify distinct subgroups
      of elders based on their CES-D scores from 1998-2008. Group membership was used
      to predict self-rated oral health, overall mouth condition (problems with
      bleeding gums, gum sensitivity, and food avoidance), and edentulism in 2008.
      RESULTS: Three distinct subgroups were identified using zero-inflated Poisson
      regression models: (i) minimal depressive symptoms over the study period (43%),
      (ii) low but generally stable level of depressive symptoms (41%), and (iii)
      moderate symptoms and higher CES-D scores than the other groups over the 10 years
      (16%). Controlling for demographic and health variables and edentulism status,
      having a trajectory of moderate symptoms was associated with poorer mouth
      condition (p < 0.0001) and poorer self-rated oral health (p = 0.0003) compared
      with those with minimal symptoms. Having low levels of depressive symptoms was
      not significantly associated with these two outcomes. Group membership was not
      significantly associated with the probability of edentulism. CONCLUSIONS: Chronic
      moderate depressive symptoms are associated with poorer oral health in older
      adults.

PMID- 25962828
TI  - Detection of Vibrio cholerae by isothermal cross-priming amplification combined
      with nucleic acid detection strip analysis.
AB  - Vibrio cholerae is a water- and food-borne human pathogen, and V. cholerae
      serotypes O1 and O139 have attracted attention because of their severe
      pathogenesis. However, non-O1, non-O139 cholera vibrios (NCVs) were also recently
      recognized as having virulence properties. In this study, we developed a cross
      priming amplification (CPA) method for the detection of all serotypes of V.
      cholerae. The specificity of the CPA method was tested using a panel of 60
      different bacterial strains. All of the V. cholerae strains showed positive
      results, and 41 other types of bacteria gave negative results. The limit of
      detection of the CPA method was 79.28 fg of genomic DNA, 4.2 * 10(2) CFU/ml for
      bacteria in pure culture, and 5.6 CFU per 25 g of sample with pre-enrichment.
      This method showed a higher sensitivity than the loop-mediated isothermal
      amplification (LAMP) method did and was more convenient to perform. These results
      indicate that the CPA method can be used for the rapid preliminary screening of
      V. cholerae.

PMID- 25962829
TI  - Acetic acid-assisted hydrothermal fractionation of empty fruit bunches for high
      hemicellulosic sugar recovery with low byproducts.
AB  - Xylose, mannose, and galactose (xmg) recovery from empty fruit bunches using
      acetic acid-assisted hydrothermal (AAH) fractionation method was investigated.
      Acetic acid has been demonstrated to be effective in xmg recovery in comparison
      with the liquid hot-water (LHW) fractionation. The maximum xmg recovery yield
      (50.7 %) from the empty fruit bunch (EFB) was obtained using AAH fractionation at
      optimum conditions (6.9 wt.% acetic acid at 170  degrees C and for 18 min);
      whereas, only 16.2 % of xmg recovery was obtained from the LHW fractionation at
      the same reaction conditions (170  degrees C and 18 min). Releasing out the
      glucose from EFB was kept at low level (<1.0 %) through all tested conditions and
      consequently negligible 5-HMF and formic acid were analyzed in the hydrolyzate.
      The production of furfural was also resulted with extremely low level (1.0 g/L).

PMID- 25962830
TI  - Editorial: Consent to treatment: Supreme Court discards Bolam principle.

PMID- 25962831
TI  - Altered Medial Frontal and Superior Temporal Response to Implicit Processing of
      Emotions in Autism.
AB  - Interpreting emotional expressions appropriately poses a challenge for
      individuals with autism spectrum disorder (ASD). In particular, difficulties with
      emotional processing in ASD are more pronounced in contexts where emotional
      expressions are subtle, automatic, and reflexive-that is, implicit. In contrast,
      explicit emotional processing, which requires the cognitive evaluation of an
      emotional experience, appears to be relatively intact in individuals with ASD. In
      the present study, we examined the brain activation and functional connectivity
      differences underlying explicit and implicit emotional processing in age- and IQ
      matched adults with (n = 17) and without (n = 15) ASD. Results indicated: (1)
      significantly reduced levels of brain activation in participants with ASD in
      medial prefrontal cortex (MPFC) and superior temporal gyrus (STG) during implicit
      emotion processing; (2) significantly weaker functional connectivity in the ASD
      group in connections of the MPFC with the amygdala, temporal lobe, parietal lobe,
      and fusiform gyrus; (3) No group difference in performance accuracy or reaction
      time; and (4) Significant positive relationship between empathizing ability and
      STG activity in ASD but not in typically developing participants. These findings
      suggest that the neural mechanisms underlying implicit, but not explicit, emotion
      processing may be altered at multiple levels in individuals with ASD.

PMID- 25962832
TI  - A molecularly imprinted sensor based on an electrochemiluminescent membrane for
      ultratrace doxycycline determination.
AB  - A new molecularly imprinted sensor was developed based on an electroluminescent
      molecularly imprinted polymer (MIP) membrane and used for doxycycline
      determination. The MIP was prepared by electropolymerization of pyrogallol doped
      with alizarin red. An electrochemiluminescence (ECL) signal was produced by the
      oxidation of the poly-pyrogallol polymer and reaction with alizarin red. The
      luminescence intensity was enhanced by doxycycline molecules which were re
      adsorbed in cavities in MIP due to the energy transfer of the doxycycline
      oxidized intermediate to alizarin red. The changes of ECL intensities were linear
      with the concentrations of doxycycline in the range of 2 * 10(-10) to 5 * 10(-8)
      mol L(-1). The detection limit was 5.17 * 10(-11) mol L(-1). This method was
      utilized to determine doxycycline residuals in fish muscles with satisfactory
      results. 

PMID- 25962833
TI  - Author/reviewer: A case of split personality.

PMID- 25962834
TI  - Evidence synthesis for count distributions based on heterogeneous and incomplete
      aggregated data.
AB  - The analysis of count data is commonly done using Poisson models. Negative
      binomial models are a straightforward and readily motivated generalization for
      the case of overdispersed data, that is, when the observed variance is greater
      than expected under a Poissonian model. Rate and overdispersion parameters then
      need to be considered jointly, which in general is not trivial. Here, we are
      concerned with evidence synthesis in the case where the reporting of data is
      rather heterogeneous, that is, events are reported either in terms of mean event
      counts, the proportion of event-free patients, or rate estimates and standard
      errors. Either figure carries some information about the relevant parameters, and
      it is the joint modeling that allows for coherent inference on the parameters of
      interest. The methods are motivated and illustrated by a systematic review in
      chronic obstructive pulmonary disease. 

PMID- 25962835
TI  - A multi-view genomic data simulator.
AB  - BACKGROUND: OMICs technologies allow to assay the state of a large number of
      different features (e.g., mRNA expression, miRNA expression, copy number
      variation, DNA methylation, etc.) from the same samples. The objective of these
      experiments is usually to find a reduced set of significant features, which can
      be used to differentiate the conditions assayed. In terms of development of novel
      feature selection computational methods, this task is challenging for the lack of
      fully annotated biological datasets to be used for benchmarking. A possible way
      to tackle this problem is generating appropriate synthetic datasets, whose
      composition and behaviour are fully controlled and known a priori. RESULTS: Here
      we propose a novel method centred on the generation of networks of interactions
      among different biological molecules, especially involved in regulating gene
      expression. Synthetic datasets are obtained from ordinary differential equations
      based models with known parameters. Our results show that the generated datasets
      are well mimicking the behaviour of real data, for popular data analysis methods
      are able to selectively identify existing interactions. CONCLUSIONS: The proposed
      method can be used in conjunction to real biological datasets in the assessment
      of data mining techniques. The main strength of this method consists in the full
      control on the simulated data while retaining coherence with the real biological
      processes. The R package MVBioDataSim is freely available to the scientific
      community at http://neuronelab.unisa.it/?p=1722.

PMID- 25962836
TI  - Hybrid position/force control of an active handheld micromanipulator for membrane
      peeling.
AB  - BACKGROUND: Peeling procedures in retinal surgery require micron-scale
      manipulation and control of sub-tactile forces. METHODS: Hybrid position/force
      control of an actuated handheld microsurgical instrument is presented as a means
      for simultaneously improving positioning accuracy and reducing forces to prevent
      avoidable trauma to tissue. The system response was evaluated, and membrane
      peeling trials were performed by four test subjects in both artificial and animal
      models. RESULTS: Maximum force was reduced by 56% in both models compared with
      position control. No statistically significant effect on procedure duration was
      observed. CONCLUSIONS: A hybrid position/force control system has been
      implemented that successfully attenuates forces and minimizes unwanted excursions
      during microsurgical procedures such as membrane peeling. Results also suggest
      that improvements in safety using this technique may be attained without
      increasing the duration of the procedure.

PMID- 25962838
TI  - Quality of Anticoagulation With Vitamin K Antagonists.
AB  - BACKGROUND: Vitamin K antagonists (VKA) have a narrow therapeutic range, and
      literature analysis reveals poor quality of anticoagulation control. We sought to
      assess the prevalence of poor anticoagulant control in patients under VKA
      treatment in the prevention of stroke for atrial fibrillation (AF). HYPOTHESIS:
      Control of anticoagulation with VKA is inadequate in a high percentage of
      patients with AF. METHODS: Patients with AF under VKA treatment were
      prospectively recruited in this observational registry. The sample comprised 948
      patients. The estimated time spent in the therapeutic range (TTR) was calculated,
      and variables related with a TTR >65% were analyzed. RESULTS: Mean age was 73.8
      +/- 9.4 years, and 42.5% of the patients were women. Mean TTR was 63.77% +/-
      23.80% for the direct method and 60.27% +/- 24.48% for the Rosendaal method.
      Prevalence of poor anticoagulation control was 54%. Variables associated with
      good anticoagulation control were university studies (odds ratio [OR]: 1.99, 95%
      confidence interval [CI]: 1.08-3.64), chronic hepatic disease (OR: 8.15, 95% CI:
      1.57-42.24), low comorbidity expressed as Charlson index (OR: 0.87, 95% CI: 0.76
      0.99), no previous cardiac disease (OR: 0.64, 95% CI: 0.41-0.98), lower risk of
      bleeding assessed as hypertension, abnormal renal/liver function, stroke,
      bleeding history or predisposition, labile international normalized ratio,
      elderly age, and use of drugs or alcohol (HAS-BLED; OR: 0.81, 95% CI: 0.69-0.95),
      and lower heart rate (OR: 0.99, 95% CI: 0.98-0.99). CONCLUSIONS: Patients who
      receive VKA to prevent stroke for AF spend less than half the time within
      therapeutic range.

PMID- 25962839
TI  - Exercise training modifies gut microbiota in normal and diabetic mice.
AB  - Cecal microbiota from type 2 diabetic (db/db) and control (db/(+)) mice was
      obtained following 6 weeks of sedentary or exercise activity. qPCR analysis
      revealed a main effect of exercise, with greater abundance of select Firmicutes
      species and lower Bacteroides/Prevotella spp. in both normal and diabetic
      exercised mice compared with sedentary counterparts. Conversely, Bifidobacterium
      spp. was greater in exercised normal but not diabetic mice (exercise * diabetes
      interaction). How exercise influences gut microbiota requires further
      investigation. 

PMID- 25962837
TI  - Transcriptional profiling and targeted proteomics reveals common molecular
      changes associated with cigarette smoke-induced lung emphysema development in
      five susceptible mouse strains.
AB  - BACKGROUND: Mouse models are useful for studying cigarette smoke (CS)-induced
      chronic pulmonary pathologies such as lung emphysema. To enhance translation of
      large-scale omics data from mechanistic studies into pathophysiological changes,
      we have developed computational tools based on reverse causal reasoning (RCR).
      OBJECTIVE: In the present study we applied a systems biology approach leveraging
      RCR to identify molecular mechanistic explanations of pathophysiological changes
      associated with CS-induced lung emphysema in susceptible mice. METHODS: The lung
      transcriptomes of five mouse models (C57BL/6, ApoE (-/-) , A/J, CD1, and Nrf2 (-/
      ) ) were analyzed following 5-7 months of CS exposure. RESULTS: We predicted 39
      molecular changes mostly related to inflammatory processes including known key
      emphysema drivers such as NF-kappaB and TLR4 signaling, and increased levels of
      TNF-alpha, CSF2, and several interleukins. More importantly, RCR predicted
      potential molecular mechanisms that are less well-established, including
      increased transcriptional activity of PU.1, STAT1, C/EBP, FOXM1, YY1, and N-COR,
      and reduced protein abundance of ITGB6 and CFTR. We corroborated several
      predictions using targeted proteomic approaches, demonstrating increased
      abundance of CSF2, C/EBPalpha, C/EBPbeta, PU.1, BRCA1, and STAT1. CONCLUSION:
      These systems biology-derived candidate mechanisms common to susceptible mouse
      models may enhance understanding of CS-induced molecular processes underlying
      emphysema development in mice and their relevancy for human chronic obstructive
      pulmonary disease.

PMID- 25962840
TI  - Prognostic evaluation of biofeedback response in patients treated for anorectal
      malformation.
AB  - PURPOSE: Functional bowel outcome in patients with anorectal malformation often
      is poor. For fecal incontinence resulting from sphincter dysfunction, biofeedback
      (BFB) training appears to be effective. The aim of study was to investigate the
      bowel function in incontinent children treated for ARM, using a clinical score, a
      manometric and pelvic magnetic resonance evaluation, in order to establish
      predictive parameters of response after BFB. METHODS: 25 children (median age of
      6.5 years) with true fecal incontinence were evaluated by clinical score,
      anorectal manometry and magnetic resonance imaging (MRI). According to these
      evaluations patients were divided in 4 groups: group 1 (favorables manometry and
      MRI); group 2 (favorable manometry and unfavorable MRI); group 3 (unfavorable
      manometry and favorable MRI); group 4 (unfavorables manometry and MRI). All
      groups started a cycle of BFB and six months after end of BFB, were reevaluated
      by clinical score and manometry. RESULTS: The overall response to BFB was
      excellent in 44%, discrete in 40% and poor in 16%; a better response was found in
      groups 1 and 2 than groups 3 and 4. The differences between groups before BFB
      proportionally correlated with values after BFB; a correlation with genitourinary
      and spinal anomalies was found. CONCLUSIONS: Our results showed that BFB is an
      effective for fecal incontinence when the assessment pretreatment (functional and
      morphologic) is favorable; the manometry can evaluate the potential sphincterial
      recovery after BFB with a further prognostic benefit if correlated to morphologic
      evaluation with MRI.

PMID- 25962841
TI  - Contemporary management of recurrent pectus excavatum.
AB  - BACKGROUND: Optimal management of recurrent pectus excavatum (PE) has not been
      established. Here, we review our institutional experience in managing recurrent
      PE to evaluate long-term outcomes and propose an anatomic classification of
      recurrences, and a decision-making algorithm. METHODS: Clinical records of
      patients undergoing repair of recurrent PE (1996-2011) were reviewed. Univariate
      and multivariate logistic regression analyses were employed to examine patient
      characteristics as potential predictors for re-recurrence. RESULTS: Eighty-five
      patients with recurrent PE were identified during the study period. The initial
      operation was a Ravitch procedure in 85% of cases. Revision procedures were most
      frequently Nuss repairs (N=73, 86%), with remaining cases managed via open
      approach. Overall cosmetic and functional results were satisfactory in 67
      patients (91.8%) managed with Nuss and in 7 (58%) patients managed with other
      techniques. Seven (8%) patients required additional surgical revision.
      Multivariate analysis identified no statistically significant patient or
      procedural factors predictive of re-recurrence. CONCLUSION: This study
      demonstrates that the Nuss procedure can be an effective intervention for
      recurrent pectus excavatum, regardless of the initial repair technique. However,
      open repair remains valuable when managing severe cases with abnormalities of the
      sternocostal junction and cartilage regrowth under the sternum.

PMID- 25962842
TI  - Influence of hospital and patient location on early postoperative outcomes after
      appendectomy and pyloromyotomy.
AB  - BACKGROUND: The effects of hospital location and designation on postoperative
      pediatric outcomes remain unclear. We hypothesized that urban hospital outcomes
      would be superior to rural hospitals, and that outcomes at urban centers would
      differ for children from rural versus urban counties. METHODS: Retrospective
      cohort study of children undergoing appendectomy (n=129,507) and pyloromyotomy
      (n=13,452) using the 2006/2009 KID databases. Hospitals were characterized by
      specialty designation and classified as urban/rural. County of residence was
      classified as urban/rural. Outcomes included complications and length of stay.
      Multivariate regression models were used to adjust for confounding. RESULTS:
      Among appendectomy patients, treatment at urban hospitals was associated with
      reduced odds of any postoperative complication (OR=0.77, 95% C.I. 0.70-0.85) and
      anesthesia-related complications (OR=0.72, 95% C.I. 0.57-0.91). This association
      was strongest in the youngest children (<5 years) and at children's hospitals.
      For pyloromyotomy patients, urban hospitals were associated with reduced odds of
      any complication (OR=0.43, 95% C.I. 0.24-0.75), anesthesia-related complications
      (OR=0.14, 95% C.I. 0.05-0.37), and duodenal perforation (OR=0.46, 95% C.I. 0.19
      1.07). These associations were most significant at children's hospitals.
      CONCLUSIONS: Postoperative outcomes appear to be improved at urban specialty
      hospitals relative to rural hospitals for certain common pediatric procedures.
      Identification of the factors driving this association may help inform resource
      optimization efforts in pediatric surgery.

PMID- 25962843
TI  - Single-staged surgical approach in congenital diaphragmatic hernia associated
      with esophageal atresia.
AB  - BACKGROUND: The coexistence of congenital diaphragmatic hernia (CDH) with
      esophageal atresia (EA) has only been reported occasionally in literature. Series
      of patients from a single institution with comparison of different postnatal
      therapeutic approaches have not been reported. We describe our management in this
      unique cohort of patients and discuss the procedures that can lead to successful
      outcomes in this association of congenital anomalies. METHODS: The surgical
      approaches and outcome of six neonates with CDH associated with EA and distal
      tracheo-esophageal fistula (TEF) are discussed. RESULTS: Five newborns were
      treated surgically, while one patient with trisomy 18 only received palliative
      treatment. In four patients TEF was ligated during laparotomy for CDH repair.
      Secondary surgery was performed for correction of EA via thoracotomy after 4-6
      weeks (primary anastomosis in two patients, Foker's-technique in one patient, one
      patient deceased prior to secondary surgery). All three surviving patients
      required fundoplication due to severe gastro-esophageal reflux during the first
      year of life. Two patients also required dilatation for anastomotic stricture. In
      one preterm infant correction of both malformations was accomplished during one
      surgical intervention. The herniated organs were eventrated and temporarily
      placed into a silastic bag to allow a mediastinal shift to the left. Thus a
      continuous ventilation of the right lung with minimal compression and sufficient
      oxygenation was possible during esophageal repair via a right-sided thoracotomy
      and extrapleural approach. No further surgery was required so far. CONCLUSIONS:
      Definitive surgical correction in newborns with CDH and EA was so far
      accomplished with multiple surgical interventions. Ligation of TEF via an
      abdominal approach with repair of CDH followed by delayed repair of EA is prone
      to stenosis and gastro-esophageal reflux due to loss of esophageal length. With a
      new combination of established surgical methods a single-staged correction of
      both malformations is possible. This new approach might help to preserve
      sufficient length of esophagus to accomplish primary anastomosis without tension
      and therefore avoid long-term morbidity and repetitive surgeries.

PMID- 25962844
TI  - Coordination polymer flexibility leads to polymorphism and enables a crystalline
      solid-vapour reaction: a multi-technique mechanistic study.
AB  - Despite an absence of conventional porosity, the 1D coordination polymer [Ag4 (O2
      C(CF2 )2 CF3 )4 (TMP)3 ] (1; TMP=tetramethylpyrazine) can absorb small alcohols
      from the vapour phase, which insert into Ag?O bonds to yield coordination
      polymers [Ag4 (O2 C(CF2 )2 CF3 )4 (TMP)3 (ROH)2 ] (1-ROH; R=Me, Et, iPr). The
      reactions are reversible single-crystal-to-single-crystal transformations. Vapour
      solid equilibria have been examined by gas-phase IR spectroscopy (K=5.68(9)*10(
      5) (MeOH), 9.5(3)*10(-6) (EtOH), 6.14(5)*10(-5) (iPrOH) at 295 K, 1 bar). Thermal
      analyses (TGA, DSC) have enabled quantitative comparison of two-step reactions 1
      ROH->1->2, in which 2 is the 2D coordination polymer [Ag4 (O2 C(CF2 )2 CF3 )4
      (TMP)2 ] formed by loss of TMP ligands exclusively from singly-bridging sites.
      Four polymorphic forms of 1 (1-A(LT) , 1-A(HT) , 1-B(LT) and 1-B(HT) ; HT=high
      temperature, LT=low temperature) have been identified crystallographically. In
      situ powder X-ray diffraction (PXRD) studies of the 1-ROH->1->2 transformations
      indicate the role of the HT polymorphs in these reactions. The structural
      relationship between polymorphs, involving changes in conformation of
      perfluoroalkyl chains and a change in orientation of entire polymers (A versus B
      forms), suggests a mechanism for the observed reactions and a pathway for guest
      transport within the fluorous layers. Consistent with this pathway, optical
      microscopy and AFM studies on single crystals of 1-MeOH/1-A(HT) show that cracks
      parallel to the layers of interdigitated perfluoroalkyl chains develop during the
      MeOH release/uptake process. 

PMID- 25962846
TI  - Tumor growth prediction with reaction-diffusion and hyperelastic biomechanical
      model by physiological data fusion.
AB  - The goal of tumor growth prediction is to model the tumor growth process, which
      can be achieved by physiological modeling and model personalization from clinical
      measurements. Although image-driven frameworks have been proposed with promising
      results, several issues such as infinitesimal strain assumptions, complicated
      personalization procedures, and the lack of functional information, may limit
      their prediction accuracy. In view of these issues, we propose a framework for
      pancreatic neuroendocrine tumor growth prediction, which comprises a FEM-based
      tumor growth model with coupled reaction-diffusion equation and nonlinear
      biomechanics. Physiological data fusion of structural and functional images is
      used to improve the subject-specificity of model personalization, and a
      derivative-free global optimization algorithm is adopted to facilitate the
      complicated model and accommodate flexible choices of objective functions. With
      this flexibility, we propose an objective function accounting for both the tumor
      volume difference and the root-mean-squared error of intracellular volume
      fractions. Experiments were performed on synthetic and clinical data to verify
      the parameter estimation capability and the prediction performance. Comparisons
      of using different biomechanical models and objective functions were also
      performed. From the experimental results of eight patient data sets, the average
      recall, precision, Dice coefficient, and relative volume difference between
      predicted and measured tumor volumes were 84.5 +/- 6.9%, 85.8 +/- 8.2%, 84.6 +/-
      1.7%, and 14.2 +/- 8.4%, respectively. 

PMID- 25962845
TI  - Regularized outcome weighted subgroup identification for differential treatment
      effects.
AB  - To facilitate comparative treatment selection when there is substantial
      heterogeneity of treatment effectiveness, it is important to identify subgroups
      that exhibit differential treatment effects. Existing approaches model outcomes
      directly and then define subgroups according to interactions between treatment
      and covariates. Because outcomes are affected by both the covariate-treatment
      interactions and covariate main effects, direct modeling outcomes can be hard due
      to model misspecification, especially in presence of many covariates.
      Alternatively one can directly work with differential treatment effect
      estimation. We propose such a method that approximates a target function whose
      value directly reflects correct treatment assignment for patients. The function
      uses patient outcomes as weights rather than modeling targets. Consequently, our
      method can deal with binary, continuous, time-to-event, and possibly contaminated
      outcomes in the same fashion. We first focus on identifying only directional
      estimates from linear rules that characterize important subgroups. We further
      consider estimation of comparative treatment effects for identified subgroups. We
      demonstrate the advantages of our method in simulation studies and in analyses of
      two real data sets. 

PMID- 25962847
TI  - Tumor suppressor Menin acts as a corepressor of LXRalpha to inhibit hepatic
      lipogenesis.
AB  - Menin, encoded by the MEN1 gene, was initially identified as a tumor suppressor
      for endocrine neoplasia. Our previous report showed that Menin enhances PPARalpha
      transactivity preventing triglyceride accumulation in the liver. Here, we further
      explore the role of Menin in liver steatosis. Transient transfection assays
      demonstrate that Menin inhibits the transcriptional activity of nuclear receptor
      liver X receptor alpha (LXRalpha). Accordingly, Menin overexpression results in
      reduced expression of LXRalpha target genes, such as lipogenic enzymes including
      SREBP-1c, FASN and SCD-1. Co-immunoprecipitation assays revealed physical
      interaction between Menin and LXRalpha. Collectively, our data suggest that Menin
      acts as a novel corepressor of LXRalpha and functions as a negative regulator of
      hepatic lipogenesis. 

PMID- 25962849
TI  - Tuning colloidal gels by shear.
AB  - Using a powerful combination of experiments and simulations we demonstrate how
      the microstructure and its time evolution are linked with mechanical properties
      in a frustrated, out-of-equilibrium, particle gel under shear. An intermediate
      volume fraction colloid-polymer gel is used as a model system, allowing
      quantification of the interplay between interparticle attractions and shear
      forces. Rheometry, confocal microscopy and Brownian dynamics reveal that high
      shear rates, fully breaking the structure, lead after shear cessation to more
      homogeneous and stronger gels, whereas preshear at low rates creates largely
      heterogeneous weaker gels with reduced elasticity. We find that in comparison,
      thermal quenching cannot produce structural inhomogeneities under shear. We argue
      that external shear has strong implications on routes towards metastable
      equilibrium, and therefore gelation scenarios. Moreover, these results have
      strong implications for material design and industrial applications, such as
      mixing, processing and transport protocols coupled to the properties of the final
      material. 

PMID- 25962848
TI  - Directionality of electron transfer in cyanobacterial photosystem I at 298 and
      77K.
AB  - Electron transfer processes in cyanobacterial photosystem I particles from
      Synechocystis sp. PCC 6803 with a high potential naphthoquinone (2,3-dichloro-1,4
      naphthoquinone) incorporated into the A1 binding site have been studied at 298
      and 77K using time-resolved visible and infrared difference spectroscopy. The
      high potential naphthoquinone inhibits electron transfer past A1, and biphasic
      P700(+)A1(-) radical pair recombination is observed. The two phases are assigned
      to P700(+)A1B(-) and P700(+)A1A(-) recombination. Analyses of the transient
      absorption changes indicate that the ratio of A- and B-branch electron transfer
      is 95:5 at 77 K and 77:23 at 298 K.

PMID- 25962850
TI  - Surface polysaccharides and quorum sensing are involved in the attachment and
      survival of Xanthomonas albilineans on sugarcane leaves.
AB  - Xanthomonas albilineans, the causal agent of sugarcane leaf scald, is a bacterial
      plant pathogen that is mainly spread by infected cuttings and contaminated
      harvesting tools. However, some strains of this pathogen are known to be spread
      by aerial means and are able to colonize the phyllosphere of sugarcane before
      entering the host plant and causing disease. The objective of this study was to
      identify the molecular factors involved in the survival or growth of X.
      albilineans on sugarcane leaves. We developed a bioassay to test for the
      attachment of X. albilineans on sugarcane leaves using tissue-cultured plantlets
      grown in vitro. Six mutants of strain XaFL07-1 affected in surface polysaccharide
      production completely lost their capacity to survive on the sugarcane leaf
      surface. These mutants produced more biofilm in vitro and accumulated more
      cellular poly-beta-hydroxybutyrate than the wild-type strain. A mutant affected
      in the production of small molecules (including potential biosurfactants)
      synthesized by non-ribosomal peptide synthetases (NRPSs) attached to the
      sugarcane leaves as well as the wild-type strain. Surprisingly, the attachment of
      bacteria on sugarcane leaves varied among mutants of the rpf gene cluster
      involved in bacterial quorum sensing. Therefore, quorum sensing may affect
      polysaccharide production, or both polysaccharides and quorum sensing may be
      involved in the survival or growth of X. albilineans on sugarcane leaves. 

PMID- 25962851
TI  - Efficacy and community effectiveness of larvivorous fish for dengue vector
      control.
AB  - OBJECTIVE: To evaluate the efficacy and community effectiveness of larvivorous
      fish for the control of dengue vectors and dengue transmission, when used as a
      single agent or in combination with other vector control methods. METHOD:
      Comprehensive literature search of published and grey literature using PubMed,
      EMBASE (DMDI), Web of Science, WHOLIS, WILEY, LILACS, GIFT, Cochrane Library,
      ELDIS, New York Academy of Medicine Grey Literature Report and Google. All
      results were checked for duplicates and examined for eligibility. Methodological
      quality of the studies was assessed using RoBANS. RESULTS: Thirteen articles were
      considered eligible for inclusion. Incorporating a wide range of interventions
      and outcome measures, three were efficacy studies and 10 assessed community
      effectiveness. None of the studies were randomised or cluster-randomised
      controlled trials. All three efficacy studies and seven community effectiveness
      studies investigated fish as a single agent. All efficacy studies reported
      elimination of Aedes larvae from treated containers, while community
      effectiveness studies reported reductions in immature vector stages, two of which
      also detected a continuous decline over 2 years. An impact on adult mosquitoes
      was shown in only two community effectiveness studies. Reductions in dengue cases
      following intervention were reported in two studies, but it was not possible to
      attribute this to the intervention. CONCLUSION: While the use of larvivorous fish
      as a single agent or in combination with other control measures could lead to
      reductions in immature vector stages, considerable limitations in all the studies
      restricted any conclusions with respect to the evaluation of community
      effectiveness. Evidence for the community effectiveness of larvivorous fish as a
      single agent remains minimal and cluster-randomised controlled studies that
      include the assessment of impact on dengue are recommended.

PMID- 25962852
TI  - Preeclampsia is Characterized by Fetal NK Cell Activation and a Reduction in
      Regulatory T Cells.
AB  - PROBLEM: Preeclampsia affects 3-17% of pregnancies worldwide and has serious
      consequences for both the mother and the fetus. As maternal-fetal immune
      tolerance is bidirectional, fetal immunopathology may play a significant role in
      the pathogenesis of pregnancy disorders. Nevertheless, the impact of preeclampsia
      on the fetal immune system is unclear. METHOD OF STUDY: In this case-control
      study, we examined the phenotype of innate and adaptive immune cells from the
      cord blood of 3rd trimester babies born to healthy mothers and compared them to
      cord blood from 3rd trimester babies born to mothers with symptomatic
      preeclampsia. RESULTS: The ratio of CD56hi CD16- non-activated/regulatory NK
      cells to CD56lo CD16+ activated/effector NK cells as well as the proportion of
      CD4+ T cells was significantly decreased in the cord blood of babies born to
      preeclamptic mothers. The percentage of FoxP3+ Treg, especially the FoxP3lo
      populations (resting Treg and cytokine Treg), were significantly reduced.
      Importantly, this reduction in FoxP3+ Treg affected the ratio of CD8+ effector T
      cells per FoxP3+ Treg in the cord blood of babies born to preeclamptic mothers.
      CONCLUSION: These observations indicate that there are significant fetal immune
      system derangements during preeclampsia.

PMID- 25962853
TI  - A gene-expression-based neural code for food abundance that modulates lifespan.
AB  - How the nervous system internally represents environmental food availability is
      poorly understood. Here, we show that quantitative information about food
      abundance is encoded by combinatorial neuron-specific gene-expression of
      conserved TGFbeta and serotonin pathway components in Caenorhabditis elegans.
      Crosstalk and auto-regulation between these pathways alters the shape, dynamic
      range, and population variance of the gene-expression responses of daf-7
      (TGFbeta) and tph-1 (tryptophan hydroxylase) to food availability. These
      intricate regulatory features provide distinct mechanisms for TGFbeta and
      serotonin signaling to tune the accuracy of this multi-neuron code: daf-7
      primarily regulates gene-expression variability, while tph-1 primarily regulates
      the dynamic range of gene-expression responses. This code is functional because
      daf-7 and tph-1 mutations bidirectionally attenuate food level-dependent changes
      in lifespan. Our results reveal a neural code for food abundance and demonstrate
      that gene expression serves as an additional layer of information processing in
      the nervous system to control long-term physiology. 

PMID- 25962854
TI  - Tinnitus and hyperacusis involve hyperactivity and enhanced connectivity in
      auditory-limbic-arousal-cerebellar network.
AB  - Hearing loss often triggers an inescapable buzz (tinnitus) and causes everyday
      sounds to become intolerably loud (hyperacusis), but exactly where and how this
      occurs in the brain is unknown. To identify the neural substrate for these
      debilitating disorders, we induced both tinnitus and hyperacusis with an ototoxic
      drug (salicylate) and used behavioral, electrophysiological, and functional
      magnetic resonance imaging (fMRI) techniques to identify the tinnitus-hyperacusis
      network. Salicylate depressed the neural output of the cochlea, but vigorously
      amplified sound-evoked neural responses in the amygdala, medial geniculate, and
      auditory cortex. Resting-state fMRI revealed hyperactivity in an auditory network
      composed of inferior colliculus, medial geniculate, and auditory cortex with side
      branches to cerebellum, amygdala, and reticular formation. Functional
      connectivity revealed enhanced coupling within the auditory network and segments
      of the auditory network and cerebellum, reticular formation, amygdala, and
      hippocampus. A testable model accounting for distress, arousal, and gating of
      tinnitus and hyperacusis is proposed. 

PMID- 25962855
TI  - Dynamic BMP signaling polarized by Toll patterns the dorsoventral axis in a
      hemimetabolous insect.
AB  - Toll-dependent patterning of the dorsoventral axis in Drosophila represents one
      of the best understood gene regulatory networks. However, its evolutionary origin
      has remained elusive. Outside the insects Toll is not known for a patterning
      function, but rather for a role in pathogen defense. Here, we show that in the
      milkweed bug Oncopeltus fasciatus, whose lineage split from Drosophila's more
      than 350 million years ago, Toll is only required to polarize a dynamic BMP
      signaling network. A theoretical model reveals that this network has self
      regulatory properties and that shallow Toll signaling gradients are sufficient to
      initiate axis formation. Such gradients can account for the experimentally
      observed twinning of insect embryos upon egg fragmentation and might have evolved
      from a state of uniform Toll activity associated with protecting insect eggs
      against pathogens. 

PMID- 25962857
TI  - Paediatric Tracheomalacia.
AB  - Intrathoracic tracheomalacia is characterized by increased compliance of the
      central airway within the thorax. This leads to excessive dynamic collapse during
      exhalation or periods of increased intrathoracic pressure such as crying.
      Extrathoracic tracheomalacia involves dynamic collapse of the airway between the
      glottis and sternal notch that occurs during inhalation rather than exhalation.
      The tone of the posterior membrane of the trachea increases throughout
      development and childhood, as does the rigidity of the tracheal cartilage.
      Abnormalities of airway maturation result in congenital tracheomalacia. Acquired
      tracheomalacia occurs in the normally developed trachea due to trauma, external
      compression, or airway inflammation. Although tracheomalacia can be suspected by
      history, physical examination, and supportive radiographic findings, flexible
      fiberoptic bronchoscopy remains the "gold standard" for diagnosis. Current
      treatment strategies involve pharmacotherapy with cholinergic agents, positive
      pressure ventilation, and surgical repair. 

PMID- 25962856
TI  - Metacognition in Pathological Gambling and Its Relationship with Anxious and
      Depressive Symptomatology.
AB  - Gambling disorder is associated with elevated comorbidity with depressive and
      anxious disorders, and one variable that might help in the understanding of this
      association is metacognition. In the present study, the relationship between
      gambling and metacognition and the mediating role of metacognition in the
      relationship between gambling and depressive and anxious symptomatology were
      assessed. The sample comprised 124 pathological gamblers from centers that assist
      pathological gamblers and 204 participants from the general population. The
      results showed that pathological gamblers had higher levels of depressive and
      anxious symptomatology. Additionally, pathological gamblers had higher scores for
      positive beliefs about worry, negative beliefs of uncontrollability and danger,
      and beliefs about the need to control thoughts; these factors were also
      positively correlated with depressive and anxious symptomatology. Metacognition
      also fully mediated the association between gambling and depressive and anxious
      symptomatology. These results suggest that metacognition could contribute to
      explaining gambling disorder and the symptomatology associated with it. 

PMID- 25962858
TI  - The first breaths of life: imaging studies of the human infant during neonatal
      transition.
AB  - The neonatal transition during birth is characterized by major physiological
      changes in respiratory and hemodynamic function, which are predominantly
      initiated by labor, lung aeration and clamping of the umbilical cord. Lung liquid
      clearance and lung aeration are not only important for the establishment of
      functional residual capacity, but these events also trigger the significant
      decrease in pulmonary vascular resistance and increase in pulmonary blood flow.
      Clamping the umbilical cord also contributes to these hemodynamic changes by
      increasing the systemic vascular resistance and sudden loss of a large proportion
      of venous return. This results in blood flow changes both through the foramen
      ovale and ductus arteriosus and eventually leads to closure of these structures
      and the separation of the pulmonary and systemic circulations. Most of the early
      theories describing neonatal transition are based on imaging studies of human
      infants from the 1900s. Some of these theories have been disproven in more recent
      studies using more accurate and non-invasive imaging techniques. This review will
      provide an overview of the theories suggested to explain the process of liquid
      clearance and lung recruitment and also addresses new findings in this field of
      research. 

PMID- 25962859
TI  - Nelumbo nucifera leaves protect hydrogen peroxide-induced hepatic damage via
      antioxidant enzymes and HO-1/Nrf2 activation.
AB  - Naturally occurring phenolic compounds are widely found in plants. Here, the
      phenolic composition and hepatoprotective effect of the butanolic extract (BE)
      from Nelumbo nucifera leaves against H2O2-induced hepatic damage in cultured
      hepatocytes were investigated. BE showed high total phenol and flavonoid
      contents, and major phenolic compounds are quercetin, catechin, ferulic acid,
      rutin, and protocatechuic acid by HPLC analysis. BE effectively scavenged 2,2
      diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azino-bis(3-ethylbenzthiazoline)-6
      sulfonic acid (ABTS) cation radicals (IC50 values of 5.21 MUg mL(-1) for DPPH and
      6.22 MUg mL(-1) for ABTS(+)) and showed strong reducing power. Pretreatment of BE
      prior to 650 MUM H2O2 exposure markedly increased cell viability and suppressed
      H2O2-induced intracellular reactive oxygen species generation and AAPH-induced
      cell membrane lipid peroxidation. In addition, BE up-regulated intracellular
      glutathione levels under normal and oxidative stress conditions. Notably, the
      hepatoprotective effect of BE was directly correlated with the increased
      expression of superoxide dismutase-1 (SOD-1) by 0.62-fold, catalase (CAT) by 0.42
      fold, and heme oxygenase-1 (HO-1) by 2.4-fold. Pretreatment of BE also increased
      the nuclear accumulation of Nrf2 by 8.1-fold indicating that increased SOD-1,
      CAT, and HO-1 expressions are Nrf2-mediated.

PMID- 25962860
TI  - Brain Networks Subserving Emotion Regulation and Adaptation after Mild Traumatic
      Brain Injury.
AB  - The majority of patients with traumatic brain injury (TBI) sustain a mild injury
      (mTBI). One out of 4 patients experiences persistent complaints, despite their
      often normal neuropsychological test results and the absence of structural brain
      damage on conventional neuroimaging. Susceptibility to develop persistent
      complaints is thought to be affected by interindividual differences in
      adaptation, which can also be influenced by preinjury psychological factors.
      Coping is a key construct of adaptation and refers to strategies to deal with new
      situations and serious life events. An important element of coping is the ability
      to regulate emotions and stress. The prefrontal cortex is a crucial area in this
      regulation process, given that it exerts a top-down influence on the amygdala and
      other subcortical structures involved in emotion processing. However, little is
      known about the role of the prefrontal cortex and associated brain networks in
      emotion regulation and adaptation post-mTBI. Especially, the influence of
      prefrontal dysfunction on development of persistent postconcussive complaints is
      poorly understood. In this article, we aim to integrate findings from functional
      and structural MRI studies on this topic. Alterations within the default mode,
      executive and salience network have been found in relation to complaints post
      mTBI. Dysfunction of the medial prefrontal cortex may impair network dynamics for
      emotion regulation and adaptation post-mTBI, resulting in persistent post
      concussive complaints. 

PMID- 25962861
TI  - Interrater and Intrarater Reliability and Validity of 3 Measurement Methods for
      Shoulder-Position Sense.
AB  - CONTEXT: Joint-position sense (JPS) plays a critical role in the stability of
      shoulder joint. Restoration of JPS is essential to improve rehabilitation
      outcomes in individuals with shoulder injury. However, the number of affordable
      and reliable shoulder-JPS measurement methods for everyday clinical practice is
      limited. OBJECTIVE: To estimate reliability and validity of 3 simple shoulder-JPS
      measurement methods. DESIGN: Cross-sectional study. PARTICIPANTS: 25 healthy men
      and women. MAIN OUTCOME MEASURE: Absolute-error scores of JPS in 3 ranges of
      shoulder flexion (low, mid, and high), measured with a laser pointer, an
      inclinometer, and a goniometer in 2 separate sessions (48 h apart). RESULTS:
      Overall interrater and intrarater intraclass correlation coefficients were .86
      and .78 for the laser pointer, .67 and .70 for the inclinometer, and .60 and .50
      for the goniometer, respectively. There was excellent reliability in the low
      range for the laser pointer and inclinometer methods, but fair to good and poor
      reliability in mid- and high ranges, respectively. All methods showed strong
      validity. CONCLUSION: The laser pointer and inclinometer JPS measurement methods
      are reliable and can be used by clinicians during rehabilitation of shoulder
      injuries.

PMID- 25962862
TI  - [Amputations--current developments].

PMID- 25962863
TI  - Prognostic value of heart valve calcifications for cardiovascular events in a
      lung cancer screening population.
AB  - To assess the prognostic value of aortic valve and mitral valve/annulus
      calcifications for cardiovascular events in heavily smoking men without a history
      of cardiovascular disease. Heavily smoking men without a cardiovascular disease
      history who underwent non-contrast-enhanced low-radiation-dose chest CT for lung
      cancer screening were included. Non-imaging predictors (age, smoking status and
      pack-years) were collected and imaging-predictors (calcium volume of the coronary
      arteries, aorta, aortic valve and mitral valve/annulus) were obtained. The
      outcome was the occurrence of cardiovascular events. Multivariable Cox
      proportional-hazards regression was used to calculate hazard-ratios (HRs) with
      95% confidence interval (CI). Subsequently, concordance-statistics were
      calculated. In total 3111 individuals were included, of whom 186 (6.0%) developed
      a cardiovascular event during a follow-up of 2.9 (Q1-Q3, 2.7-3.3) years. If
      aortic (n = 657) or mitral (n = 85) annulus/valve calcifications were present,
      cardiovascular event incidence increased to 9.0% (n = 59) or 12.9% (n = 11),
      respectively. HRs of aortic and mitral valve/annulus calcium volume for
      cardiovascular events were 1.46 (95% CI, 1.09-1.84) and 2.74 (95% CI, 0.92-4.56)
      per 500 mm(3). The c-statistic of a basic model including age, pack-years,
      current smoking status, coronary and aorta calcium volume was 0.68 (95% CI, 0.63
      0.72), which did not change after adding heart valve calcium volume. Aortic valve
      calcifications are predictors of future cardiovascular events. However, there was
      no added prognostic value beyond age, number of pack-years, current smoking
      status, coronary and aorta calcium volume for short term cardiovascular events.

PMID- 25962865
TI  - A Weighty Issue: Diminished Net Nutrition Among the U.S. Working Class in the
      Nineteenth Century.
AB  - Much has been written about the modern obesity epidemic, and historical BMIs are
      low compared with their modern counterparts. However, interpreting BMI variation
      is difficult because BMIs increase when weight increases or when stature
      decreases, and the two have different implications for human health. An
      alternative measure for net current nutritional conditions is body weight. After
      controlling for height, I find that African American and white weights decreased
      throughout the late nineteenth and early twentieth centuries. Farmers had greater
      average weights than workers in other occupations. Individuals from the South had
      taller statures, greater BMIs, and heavier weights than workers in other U.S.
      regions, indicating that even though the South had higher disease rates in the
      nineteenth century, it had better net nutritional conditions. 

PMID- 25962864
TI  - Non-invasive volumetric assessment of aortic atheroma: a core laboratory
      validation using computed tomography angiography.
AB  - Aortic atherosclerosis has been linked with worse peri- and post-procedural
      outcomes following a range of aortic procedures. Yet, there are currently no
      standardized methods for non-invasive volumetric pan-aortic plaque assessment. We
      propose a novel means of more accurately assessing plaque volume across whole
      aortic segments using computed tomography angiography (CTA) imaging. Sixty
      patients who underwent CTA prior to trans-catheter aortic valve implantation were
      included in this analysis. Specialized software analysis (3mensio VascularTM, Pie
      Medical, Maastricht, Netherlands) was used to reconstruct images using a
      centerline approach, thus creating true cross-sectional aortic images, akin to
      those images produced with intravascular ultrasonography. Following aortic
      segmentation (from the aortic valve to the renal artery origin), atheroma areas
      were measured across multiple contiguous evenly spaced (10 mm) cross-sections.
      Percent atheroma volume (PAV), total atheroma volume (TAV) and calcium score were
      calculated. In our populations (age 79.9 +/- 8.5 years, male 52 %, diabetes 27 %,
      CAD 84 %, PVD 20 %), mean +/- SD number of cross sections measured for each
      patient was 35.1 +/- 3.5 sections. Mean aortic PAV and TAV were 33.2 +/- 2.51 %
      and 83,509 +/- 17,078 mm(3), respectively. Median (IQR) calcium score was 1.5
      (0.7-2.5). Mean (SD) inter-observer coefficient of variation and agreement for
      plaque area among 4 different analysts was 14.1 (5.4), and the mean (95 % CI)
      Lin's concordance correlation coefficient was 0.79 (0.62-0.89), effectively
      simulating a Core Laboratory scenario. We provide an initial validation of cross
      sectional volumetric aortic atheroma assessment using CTA. This proposed
      methodology highlights the potential for utilizing non-invasive aortic plaque
      imaging for risk prediction across a range of clinical scenarios.

PMID- 25962866
TI  - Bayesian Population Forecasting: Extending the Lee-Carter Method.
AB  - In this article, we develop a fully integrated and dynamic Bayesian approach to
      forecast populations by age and sex. The approach embeds the Lee-Carter type
      models for forecasting the age patterns, with associated measures of uncertainty,
      of fertility, mortality, immigration, and emigration within a cohort projection
      model. The methodology may be adapted to handle different data types and sources
      of information. To illustrate, we analyze time series data for the United Kingdom
      and forecast the components of population change to the year 2024. We also
      compare the results obtained from different forecast models for age-specific
      fertility, mortality, and migration. In doing so, we demonstrate the flexibility
      and advantages of adopting the Bayesian approach for population forecasting and
      highlight areas where this work could be extended. 

PMID- 25962867
TI  - Black-White Differences in Attitudes Related to Pregnancy Among Young Women.
AB  - In this article, we use newly available data from the Relationship Dynamics and
      Social Life (RDSL) study to compare a wide range of attitudes related to
      pregnancy for 961 black and white young women. We also investigate the extent to
      which race differences are mediated by, or net of, family background, childhood
      socioeconomic status (SES), adolescent experiences related to pregnancy, and
      current SES. Compared with white women, black women generally have less positive
      attitudes toward young nonmarital sex, contraception, and childbearing, and have
      less desire for sex in the upcoming year. This is largely because black women are
      more religious than white women and partly because they are more
      socioeconomically disadvantaged in young adulthood. However, in spite of these
      less positive attitudes, black women are more likely to expect sex without
      contraception in the next year and to expect more positive consequences if they
      were to become pregnant, relative to white women. This is largely because,
      relative to white women, black women had higher rates of sex without
      contraception in adolescence and partly because they are more likely to have
      grown up with a single parent. It is unclear whether attitudes toward
      contraception and pregnancy preceded or are a consequence of adolescent sex
      without contraception. Some race differences remain unexplained; net of all
      potential mediators in our models, black women have less desire for sex in the
      upcoming year, but they are less willing to refuse to have sex with a partner if
      they think it would make him angry and they expect more positive personal
      consequences of a pregnancy, relative to white women. In spite of these
      differences, black women's desires to achieve and to prevent pregnancy are very
      similar to white women's desires. 

PMID- 25962868
TI  - Deep pyoderma caused by Burkholderia cepacia complex associated with ciclosporin
      administration in dogs: a case series.
AB  - BACKGROUND: Bacteria of the Burkholderia cepacia complex (Bcc) are ubiquitous
      Gram-negative bacilli associated with fatal nosocomial infections in humans;
      multi-antibiotic resistance makes this organism a serious threat in hospital
      settings. OBJECTIVE: To describe the historical, clinicopathological and
      treatment characteristics of Bcc-associated deep skin infections in dogs.
      ANIMALS: Six dogs with skin infections in which skin bacterial cultures resulted
      in pure growth of Bcc. METHODS: Retrospective study with review of medical
      records and skin biopsies. RESULTS: All dogs were receiving oral ciclosporin at
      the time of skin infection development. All dogs were castrated males and four of
      six were West Highland white terriers. Cutaneous lesions consistent with deep
      pyoderma were confined mainly to the trunk. In all dogs skin cytology revealed a
      strong inflammatory response, with moderate to abundant numbers of intracellular
      (neutrophils and macrophages) and extracellular bacilli. In three dogs
      histopathology showed a multifocal, nodular to coalescing pyogranulomatous
      dermatitis associated with multifocal folliculitis and furunculosis. Tissue
      Giemsa and Gram stains identified numerous Gram-negative rods within macrophages.
      Antimicrobial susceptibility testing revealed multidrug-resistant Bcc strains
      with sensitivity to trimethoprim/sulfonamides in all dogs and to marbofloxacin,
      piperacillin and ceftazidime in three dogs. Successful treatment was achieved in
      all dogs using trimethoprim/sulfonamides or quinolones (marbofloxacin,
      ciprofloxacin) or doxycycline in conjunction with ciclosporin withdrawal.
      CONCLUSIONS AND CLINICAL IMPORTANCE: Clinicians should be aware of the rare
      potential for Bcc-associated deep skin infections in dogs receiving oral
      ciclosporin. Owners should be made conscious of the potential transmission risk
      to humans or other animals.

PMID- 25962869
TI  - Differences in childhood leukemia incidence and survival between Southern
      Thailand and the United States: a population-based analysis.
AB  - BACKGROUND: Childhood leukemia incidence and survival varies globally, and this
      variation may be attributed to environmental risk factors, genetics, and/or
      disparities in diagnosis and treatment. PROCEDURE: We analyzed childhood leukemia
      incidence and survival trends in children aged 0-19 years from 1990 to 2011 in
      Songkhla, Thailand (n = 316) and compared these results to US data from the
      Surveillance, Epidemiology, and End Results (SEER) registry (n = 6,738). We
      computed relative survival using Ederer II and estimated survival functions using
      the Kaplan-Meier method. Changes in incidence and 5-year survival by year of
      diagnosis were evaluated using joinpoint regression and are reported as annual
      percent changes (APC). RESULTS: The age-standardized incidence of leukemia was
      3.2 and 4.1 cases per 100,000 in Songkhla and SEER-9, respectively. In Songkhla,
      incidence from 1990 to 2011 significantly increased for leukemia (APC = 1.7%, P =
      0.031) and acute lymphoblastic leukemia (ALL) (APC = 1.8%, P = 0.033). Acute
      myeloid leukemia (AML) incidence significantly increased (APC = 4.2%, P = 0.044)
      and was significantly different from the US (P = 0.026), where incidence was
      stable during the same period (APC = 0.3%, P = 0.541). The overall 5-year
      relative survival for leukemia was lower than that reported in the US (43 vs.
      79%). Five-year survival significantly improved by at least 2% per year from 1990
      to 2011 in Songkhla for leukemia, ALL, and AML (P < 0.050). CONCLUSIONS: While
      leukemia and ALL incidence increased in Songkhla, differences in leukemia trends,
      particularly AML incidence, may suggest etiologic or diagnostic differences
      between Songkhla and the US. This work highlights the importance of evaluating
      childhood cancer trends in low- and middle-income countries.

PMID- 25962870
TI  - Averaging methods for extracting representative waveforms from motor unit action
      potential trains.
AB  - In the context of quantitative electromyography (EMG), it is of major interest to
      obtain a waveform that faithfully represents the set of potentials that
      constitute a motor unit action potential (MUAP) train. From this waveform,
      various parameters can be determined in order to characterize the MUAP for
      diagnostic analysis. The aim of this work was to conduct a thorough, in-depth
      review, evaluation and comparison of state-of-the-art methods for composing
      waveforms representative of MUAP trains. We evaluated nine averaging methods:
      Ensemble (EA), Median (MA), Weighted (WA), Five-closest (FCA), MultiMUP (MMA),
      Split-sweep median (SSMA), Sorted (SA), Trimmed (TA) and Robust (RA) in terms of
      three general-purpose signal processing figures of merit (SPMF) and seven
      clinically-used MUAP waveform parameters (MWP). The convergence rate of the
      methods was assessed as the number of potentials per MUAP train (NPM) required to
      reach a level of performance that was not significantly improved by increasing
      this number. Test material comprised 78 MUAP trains obtained from the tibialis
      anterioris of seven healthy subjects. Error measurements related to all SPMF and
      MWP parameters except MUAP amplitude descended asymptotically with increasing NPM
      for all methods. MUAP amplitude showed a consistent bias (around 4% for EA and SA
      and 1-2% for the rest). MA, TA and SSMA had the lowest SPMF and MWP error
      figures. Therefore, these methods most accurately preserve and represent MUAP
      physiological information of utility in clinical medical practice. The other
      methods, particularly WA, performed noticeably worse. Convergence rate was
      similar for all methods, with NPM values averaged among the nine methods, which
      ranged from 10 to 40, depending on the waveform parameter evaluated. 

PMID- 25962871
TI  - Aerobic conditions increase isoprenoid biosynthesis pathway gene expression
      levels for carotenoid production in Enterococcus gilvus.
AB  - Some lactic acid bacteria that harbour carotenoid biosynthesis genes (crtNM) can
      produce carotenoids. Although aerobic conditions can increase carotenoid
      production and crtNM expression levels, their effects on the pathways that
      synthesize carotenoid precursors such as mevalonate and isoprene are not
      completely understood. In this study, we investigated whether aerobic conditions
      affected gene expression levels involved in the isoprenoid biosynthesis pathway
      that includes the mevalonate and isoprene biosynthesis pathways in Enterococcus
      gilvus using real-time quantitative reverse transcription PCR. NADH oxidase (nox)
      and superoxide dismutase (sod) gene expression levels were investigated as
      controls for aerobic conditions. The expression levels of nox and sod under
      aerobic conditions were 7.2- and 8.0-fold higher, respectively, than those under
      anaerobic conditions. Aerobic conditions concomitantly increased the expression
      levels of crtNM carotenoid biosynthesis genes. HMG-CoA synthase gene expression
      levels in the mevalonate pathway were only slightly increased under aerobic
      conditions, whereas the expression levels of HMG-CoA reductase and five other
      genes in the isoprene biosynthesis pathways were 1.2-2.3-fold higher than those
      under anaerobic conditions. These results demonstrated that aerobic conditions
      could increase the expression levels of genes involved in the isoprenoid
      biosynthesis pathway via mevalonate in E. gilvus. 

PMID- 25962872
TI  - Convertible MRI contrast: Sensing the delivery and release of anti-glioma nano
      drugs.
AB  - There is considerable interest in developing nanohybrids of imaging contrast
      agents and drugs for image-guided drug delivery. We have developed a strategy of
      utilizing manganese (Mn) to enhance the nano-encapsulation of arsenic trioxide
      (ATO). Formation of arsenite (As(3+))-Mn precipitates in liposomes generates
      magnetic susceptibility effects, reflected as dark contrast on T2-weighted MRI.
      Intriguingly, following cell uptake, the As-Mn complex decomposes in response to
      low pH in endosome-lysosome releasing ionic As(3+), the active form of ATO, and
      Mn(2+), the T1 contrast agent that gives a bright signal. Glioblastoma (GBM) is
      well known for its high resistance to chemotherapy, e.g., temozolomide (TMZ).
      Building upon the previously established phosphatidylserine (PS)-targeted
      nanoplatform that has excellent GBM-targeting specificity, we now demonstrate the
      effectiveness of the targeted nanoformulated ATO for treating TMZ-resistant GBM
      cells and the ability of the convertible Mn contrast as a surrogate revealing the
      delivery and release of ATO. 

PMID- 25962873
TI  - Federally Qualified Health Centers' Capacity and Readiness for Research
      Collaborations: Implications for Clinical-Academic-Community Partnerships.
AB  - BACKGROUND: Federally qualified health centers (FQHCs) provide a health care
      safety net for underserved populations and contribute unique expertise to
      research that could further enhance quality of patient care. The purpose of this
      research was to assess interest in, readiness to, and capacity for conducting
      research in FQHCs in South Carolina (SC). METHODS: A Web-based survey was
      administered to 20 FQHCs across SC. Fourteen representatives of FQHCs completed
      the 39-item survey that assessed research experience and interest, partnerships
      and funding, barriers and benefits to research participation, training and
      technical assistance needs, and research capacity. RESULTS: FQHCs are interested
      in conducting research. FQHCs reported that health center leadership,
      organizational benefit, active engagement of staff, and clear roles for partners
      were important factors for successful partnerships. Inequity of budget and
      resources were the greatest challenges encountered. Improved patient outcomes,
      additional resources for the center, reduction in disparities, and academic
      partnerships were considered benefits for participation. FQHCs were interested in
      training and technical assistance opportunities for research funding and best
      practices for the use of research to inform programs and services. CONCLUSIONS:
      FQHCs are willing to collaborate on research. For successful research
      partnerships, collaborators should understand FQHCs' challenges and barriers to
      participation.

PMID- 25962874
TI  - I believe I'm good at orienting myself... But is that true?
AB  - The present study aimed to analyse beliefs that men and women have with respect
      to their sense of direction (SOD) and whether they correlate with spatial
      environmental task performance. Eighty-four students filled in the short version
      of the Familiarity and Spatial Cognitive Style Scale to evaluate beliefs on their
      SOD, knowledge of the city (TK), spatial ability (SA) and wayfinding (WA) and
      performed three spatial environmental tasks. Results showed that gender did not
      predict the performance on the spatial environmental tasks, whereas it can be
      predicted by participants' beliefs related to their SOD and TK. The findings
      point out the need to identify specific training aimed at improving women's
      metacognitive skills in order to delete or reduce gender differences in SA. 

PMID- 25962875
TI  - An fMRI-Based Neural Signature of Decisions to Smoke Cannabis.
AB  - Drug dependence may be at its core a pathology of choice, defined by continued
      decisions to use drugs irrespective of negative consequences. Despite evidence of
      dysregulated decision making in addiction, little is known about the neural
      processes underlying the most clinically relevant decisions drug users make:
      decisions to use drugs. Here, we combined functional magnetic resonance imaging
      (fMRI), machine learning, and human laboratory drug administration to investigate
      neural activation underlying decisions to smoke cannabis. Nontreatment-seeking
      daily cannabis smokers completed an fMRI choice task, making repeated decisions
      to purchase or decline 1-12 placebo or active cannabis 'puffs' ($0.25-$5/puff).
      One randomly selected decision was implemented. If the selected choice had been
      bought, the cost was deducted from study earnings and the purchased cannabis
      smoked in the laboratory; alternatively, the participant remained in the
      laboratory without cannabis. Machine learning with leave-one-subject-out cross
      validation identified distributed neural activation patterns discriminating
      decisions to buy cannabis from declined offers. A total of 21 participants were
      included in behavioral analyses; 17 purchased cannabis and were thus included in
      fMRI analyses. Purchasing varied lawfully with dose and cost. The classifier
      discriminated with 100% accuracy between fMRI activation patterns for purchased
      vs declined cannabis at the level of the individual. Dorsal striatum, insula,
      posterior parietal regions, anterior and posterior cingulate, and dorsolateral
      prefrontal cortex all contributed reliably to this neural signature of decisions
      to smoke cannabis. These findings provide the basis for a brain-based
      characterization of drug-related decision making in drug abuse, including effects
      of psychological and pharmacological interventions on these processes. 

PMID- 25962876
TI  - Three Birds with One Fe3O4 Nanoparticle: Integration of Microwave Digestion,
      Solid Phase Extraction, and Magnetic Separation for Sensitive Determination of
      Arsenic and Antimony in Fish.
AB  - An environmentally friendly and fast sample treatment approach that integrates
      accelerated microwave digestion (MWD), solid phase extraction, and magnetic
      separation into a single step was developed for the determination of arsenic and
      antimony in fish samples by using Fe3O4 magnetic nanoparticles (MNPs). Compared
      to conventional microwave digestion, the consumption of HNO3 was reduced
      significantly to 12.5%, and the digestion time and temperature were substantially
      decreased to 6 min and 80  degrees C, respectively. This is largely attributed to
      Fe3O4 magnetic nanoparticles being a highly effective catalyst for rapid
      generation of oxidative radicals from H2O2, as well as an excellent absorber of
      microwave irradiation. Moreover, potential interferences from sample matrices
      were eliminated because the As and Sb species adsorbed on the nanoparticles were
      efficiently separated from the digests with a hand-held magnet prior to analysis.
      Limits of detection for arsenic and antimony were in the range of 0.01-0.06 MUg
      g(-1) and 0.03-0.08 MUg g(-1) by using hydride generation atomic fluorescence
      spectrometry, respectively, and further improved to 0.002-0.005 MUg g(-1) and
      0.005-0.01 MUg g(-1) when inductively coupled plasma mass spectrometry was used
      as a detector. The precision of replicate measurements (n = 9) was better than 6%
      by analyzing 0.1 g test sample spiked with 1 MUg g(-1) arsenic and antimony. The
      proposed method was validated by analysis of two certified reference materials
      (DORM-3 and DORM-4) with good recoveries (90%-106%). 

PMID- 25962877
TI  - Yes-associated protein regulates endothelial cell contact-mediated expression of
      angiopoietin-2.
AB  - Angiogenesis is regulated by the dynamic interaction between endothelial cells
      (ECs). Hippo-Yes-associated protein (YAP) signalling has emerged as a key pathway
      that controls organ size and tissue growth by mediating cell contact inhibition.
      However, the role of YAP in EC has not been defined yet. Here, we show expression
      of YAP in the developing front of mouse retinal vessels. YAP subcellular
      localization, phosphorylation and activity are regulated by VE-cadherin-mediated
      EC contacts. This VE-cadherin-dependent YAP phosphorylation requires
      phosphoinositide 3-kinase-Akt activation. We further identify angiopoietin-2 (ANG
      2) as a potential transcriptional target of YAP in regulating angiogenic activity
      of EC in vitro and in vivo. Overexpression of YAP-active form in EC enhances
      angiogenic sprouting, and this effect is blocked by ANG-2 depletion or soluble
      Tie-2 treatment. These findings implicate YAP as a critical regulator in
      angiogenesis and provide new insights into the mechanism coordinating junctional
      stability and angiogenic activation of ECs. 

PMID- 25962878
TI  - Dual target strategy: combining distinct non-dopaminergic treatments reduces
      neuronal cell loss and synergistically modulates L-DOPA-induced rotational
      behavior in a rodent model of Parkinson's disease.
AB  - The glutamate metabotropic receptor 5 (mGluR5) and the adenosine A2A receptor
      (A2A R) represent major non-dopaminergic therapeutic targets in Parkinson's
      disease (PD) to improve motor symptoms and slow down/revert disease progression.
      The 6-hydroxydopamine rat model of PD was used to determine/compare the
      neuroprotective and behavioral impacts of single and combined administration of
      one mGluR5 antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP), and two A2A R
      antagonists, (E)-phosphoric acid mono-[3-[8-[2-(3-methoxyphenyl)vinyl]-7-methyl
      2,6-dioxo-1-prop-2-ynyl-1,2,6,7-tetrahydropurin-3-yl]propyl] (MSX-3) and 8-ethoxy
      9-ethyladenine (ANR 94). Chronic treatment with MPEP or MSX-3 alone, but not with
      ANR 94, reduced the toxin-induced loss of dopaminergic neurons in the substantia
      nigra pars compacta. Combining MSX-3 and MPEP further improved the
      neuroprotective effect of either antagonists. At the behavioral level, ANR 94 and
      MSX-3 given alone significantly potentiated L-DOPA-induced turning behavior.
      Combination of either A2A R antagonists with MPEP synergistically increased L
      DOPA-induced turning. This effect was dose-dependent and required subthreshold
      drug concentration, which per se had no motor stimulating effect. Our findings
      suggest that co-treatment with A2A R and mGluR5 antagonists provides better
      therapeutic benefits than those produced by either drug alone. Our study sheds
      some light on the efficacy and advantages of combined non-dopaminergic PD
      treatment using low drug concentration and establishes the basis for in-depth
      studies to identify optimal doses at which these drugs reach highest efficacy.
      Combined treatment with low concentrations of known adenosine A2A receptor (A2A
      R) and metabotropic glutamate receptor (mGluR5) antagonists results in a
      therapeutic benefit and provides better results than those produced by either
      drug given alone, both in terms of motor performance and neuroprotection. Future
      trials should involve careful optimization of drug combinations and
      concentrations that may avoid the emergence of debilitating side effects and slow
      down/revert disease progression.

PMID- 25962879
TI  - Novel monoclonal antibodies against Plasmodium falciparum histidine-rich protein
      2: development and application in rapid diagnostic tests of malaria in
      hyperendemic regions of China and Myanmar.
AB  - BACKGROUND: Malaria presents a considerable threat to public health. Histidine
      rich protein 2 (HRP 2) is the major protein released into human blood upon
      infection by Plasmodium falciparum. In this study, we aimed to evaluate the
      immunogenicity of HRP 2 exon II and the efficacy of novel monoclonal antibodies
      (mAbs) against HRP 2 for Point-of-Care Test (POCT). METHODS: The recombinant
      protein was expressed in soluble form in E. coli and used to immunize mice for
      mAb production. Two IgG1 mAbs (1A5 and 1C10) with high affinity, specificity and
      sensitivity for both native and recombinant HRP 2 were selected after fusion of
      mouse spleen with myeloma cells. The affinity constant of 1A5 and 1C10 were 7.15
      and 4.91 * 10-7 L/mol, respectively. Subsequently, an immunochromatograhic assay
      was used for screening of clinical samples in endemic regions of China and
      Myanmar. RESULTS: The immunochromatographic test retrospectively showed an
      overall sensitivity of 99.07%, and specificity of 100%. Sensitivity at parasite
      densities < 200, 200-2000, and > 2000 parasites/MUL was 87.5, 98.7, and 100%,
      respectively. CONCLUSIONS: These results suggest that HRP 2 exon II contains
      immunogenic sites similar to those of the native antigen and can be used for the
      development of mAbs suitable for malaria diagnosis in endemic communities.

PMID- 25962880
TI  - Pancreatic mediastinal pseudocyst presenting as a posterior mediastinal mass with
      recurrent pleural effusions: a case report and review of the literature.
AB  - INTRODUCTION: A rare complication of chronic pancreatitis is the formation of
      single or multiple mediastinal pseudocysts, which are fueled from the pancreas
      through anatomical openings of the diaphragm. We present a rare case with a
      difficult diagnosis, treatment and potentially catastrophic complications. CASE
      PRESENTATION: A 53-year-old Caucasian man was referred to our hospital for
      further investigation and treatment of a large heterogeneous mass situated in the
      posterior mediastinum, and bilateral pleural effusions which had developed after
      recent multiple episodes of pancreatitis. He had a history of chronic alcoholism.
      Laboratory and imaging modalities established the diagnosis of a pancreatic
      mediastinal pseudocyst. CONCLUSIONS: Despite successful initial conservative
      treatment, our patient had a relapse and underwent emergency surgical
      intervention due to internal hemorrhage. We present his diagnostic and imaging
      workup, along with the multidisciplinary intervention, and a literature review
      referring to the diagnosis and treatment of mediastinal pancreatic pseudocysts.

PMID- 25962881
TI  - Older Brazilian women's experience of psychological domestic violence: a social
      phenomenological study.
AB  - BACKGROUND: Domestic violence is a global public health issue, as it is in
      Brazil. The psychological violence is one of the most prevalent forms of domestic
      violence, affecting more women than men. However, many older adults do not
      consider it as a type of domestic violence. In addiction, psychological violence
      has received little attention from researchers. So, this study aims to further
      understand the phenomenon of psychological domestic violence perpetrated by
      relatives against older adult women (60 years and older). METHODS: A qualitative
      study was conducted using a social phenomenological approach proposed by Alfred
      Schutz. In-depth interviews were conducted with 11 older Brazilian women from
      three different agencies, two in Campina Grande and one in Sao Bernardo do Campo.
      Data collection took place between November 2012 and February 2013. We performed
      data analysis using the key concepts (such as the world of everyday life, natural
      attitude, intersubjetivity, stock of knowledge, biographical situation, social
      action, motivation and typification) proposed by Alfred Schutz. RESULTS: Despite
      the fact that participants reported being psychologically abused, they also
      referred to being neglected and financially abused. They revealed being
      threatened, disrespected, neglected, financially abused, forced to do housework,
      and humiliated. Older women expressed feelings of sadness, anger, grief, and
      fear, which had negative effects on their health. Attempts by the participants to
      change their current situations were unsuccessful and resulted in feelings of
      helplessness. The abuser's behaviour will change, and leaving the abusive
      situation were two possible outcomes pointed for participants. CONCLUSIONS: A
      support network is crucial to help changing the behaviour of aggressors and/or to
      help older adult women leave the abusive situation. Further research is needed to
      understand the risk factors linked to abuse behaviours, to develop educational
      programs for the abusers, and to design social support for the victims.

PMID- 25962882
TI  - Immigration and viral hepatitis.
AB  - WHO estimates reveal that the global prevalence of viral hepatitis may be as high
      as 500 million, with an annual mortality rate of up to 1.3 million individuals.
      The majority of this global burden of disease is borne by nations of the
      developing world with high rates of vertical and iatrogenic transmission of HBV
      and HCV, as well as poor access to healthcare. In 2013, 3.2% of the global
      population (231 million individuals) migrated into a new host nation. Migrants
      predominantly originate from the developing countries of the south, into the
      developed economies of North America and Western Europe. This mass migration of
      individuals from areas of high-prevalence of viral hepatitis poses a unique
      challenge to the healthcare systems of the host nations. Due to a lack of
      universal standards for screening, vaccination and treatment of viral hepatitis,
      the burden of chronic liver disease and hepatocellular carcinoma continues to
      increase among migrant populations globally. Efforts to increase case
      identification and treatment among migrants have largely been limited to small
      outreach programs in urban centers, such that the majority of migrants with viral
      hepatitis continue to remain unaware of their infection. This review summarizes
      the data on prevalence of viral hepatitis and burden of chronic liver disease
      among migrants, current standards for screening and treatment of immigrants and
      refugees, and efforts to improve the identification and treatment of viral
      hepatitis among migrants.

PMID- 25962884
TI  - Strain ultrasound elastography for liver diseases.

PMID- 25962883
TI  - Delta hepatitis within the Veterans Affairs medical system in the United States:
      Prevalence, risk factors, and outcomes.
AB  - BACKGROUND & AIMS: Low hepatitis delta prevalence estimates in the United States
      are likely biased due to low testing rates. The objectives of this study were to
      quantify the prevalence of testing and identify factors associated with hepatitis
      D positive status among chronic hepatitis B patients in the Veterans Health
      Administration. METHODS: We performed a nationwide retrospective study of all
      veterans who tested positive for HBsAg from October 1999 to December 2013.
      Hepatitis D antibody testing results were used to stratify patients into three
      groups: HDV-positive, HDV-negative, and HDV-not tested. Demographics,
      comorbidities, additional laboratory data and clinical outcomes were compared
      across these groups of patients using standard statistical approaches. RESULTS:
      Among 25,603 patients with a positive hepatitis B surface antigen, 2175 (8.5%)
      were tested for HDV; 73 (3.4%) patients tested positive. Receiving HDV testing
      was associated with receipt of testing for HBV, HIV, and HCV. Predictors of
      positive HDV results included substance abuse and cirrhosis. Fitting a predefined
      high-risk profile (abnormal ALT with suppressed HBV DNA titers) was strongly
      associated with testing positive for HDV (OR 3.2, 95%CI 1.4-7.5). Most (59%) of
      HDV-positive patients were HCV co-infected. HDV-positive subjects had higher
      risks of all-cause mortality. Incidence rates of HCC were 2.9 fold higher in HDV
      positive relative to HDV-negative individuals (p=0.002). In adjusted analyses,
      HDV was independently associated with HCC (OR 2.1, 95%CI 1.1-3.9). CONCLUSIONS:
      Testing rates for hepatitis delta in chronic hepatitis B patients in the United
      States are inappropriately low. Approaches to increase testing for HDV
      particularly in high-risk subsets should be explored.

PMID- 25962886
TI  - The size of tibial footprint of anterior cruciate ligament and association with
      physical characteristics in Asian females.
AB  - INTRODUCTION: The tibial footprint is important for preoperative planning of
      operative technique and graft selection. Knowledge of tibial footprint in Asians
      is scant including the relationship between tibial footprint and physical
      characteristics. The aim of this study was to identify the size of the anterior
      cruciate ligament (ACL) tibial footprint and the proportion of size <14 mm, and
      to evaluate the association of tibial footprint with physical characteristics in
      Asian females. MATERIALS AND METHODS: A total of 127 patients with intact or
      minimal change in ACL were included. The tibial footprint was carefully measured
      during total knee arthroplasty. As potential predictors, leg length, femoral
      length, tibial length, and anteroposterior and mediolateral diameter of the
      proximal tibia were measured on radiographs, as well as body height and weight.
      The relationship of ACL tibial footprint length <14 mm with physical
      characteristics was analyzed using univariable and multivariable logistic
      regression. RESULTS: The tibial footprint was 13.8 mm (range 10.0-18.0) in length
      and 9.8 mm (range 6.3-13.5) in width. The proportion of footprints <14 mm in
      length was 53.5 %. Patient height, leg length, femoral length, and tibial length
      were correlated with tibial footprint. Tibial length was the best predictor of
      ACL tibial footprint length <14 mm (Odds ratio 1.75; 95 % confidence interval
      1.08-2.82). CONCLUSIONS: Tibial footprint size shows a large variation with a
      high proportion of <14 mm length. Tibial length can help predict the ACL tibial
      footprint in the preoperative planning of ACL reconstruction.

PMID- 25962887
TI  - Ebola virus outbreak, updates on current therapeutic strategies.
AB  - Filoviruses are enveloped negative-sense single-stranded RNA viruses, which
      include Ebola and Marburg viruses, known to cause hemorrhagic fever in humans
      with a case fatality of up to 90%. There have been several Ebola virus outbreaks
      since the first outbreak in the Democratic Republic of Congo in 1976 of which,
      the recent 2013-2015 epidemic in Guinea, Liberia, and Sierra Leone is the largest
      in recorded history. Within a few months of the start of the outbreak in December
      2013, thousands of infected cases were reported with a significant number of
      deaths. As of March 2015, according to the Centers for Disease Control and
      Prevention, there have been nearly 25,000 suspected cases, with 15,000 confirmed
      by laboratory testing, and over 10,000 deaths. The large number of cases and the
      high mortality rate, combined with the lack of effective Food and Drug
      Administration-approved treatments, necessitate the development of potent and
      safe therapeutic measures to combat the current and future outbreaks. Since the
      beginning of the outbreak, there have been considerable efforts to develop and
      characterize protective measures including vaccines and antiviral small
      molecules, and some have proven effective in vitro and in animal models. Most
      recently, a cocktail of monoclonal antibodies has been shown to be highly
      effective in protecting non-human primates from Ebola virus infection. In this
      review, we will discuss what is known about the nature of the virus, phylogenetic
      classification, genomic organization and replication, disease transmission, and
      viral entry and highlight the current approaches and efforts, in the development
      of therapeutics, to control the outbreak.

PMID- 25962885
TI  - Successful knowledge translation intervention in long-term care: final results
      from the vitamin D and osteoporosis study (ViDOS) pilot cluster randomized
      controlled trial.
AB  - BACKGROUND: Few studies have systematically examined whether knowledge
      translation (KT) strategies can be successfully implemented within the long-term
      care (LTC) setting. In this study, we examined the effectiveness of a
      multifaceted, interdisciplinary KT intervention for improving the prescribing of
      vitamin D, calcium and osteoporosis medications over 12-months. METHODS: We
      conducted a pilot, cluster randomized controlled trial in 40 LTC homes (21
      control; 19 intervention) in Ontario, Canada. LTC homes were eligible if they had
      more than one prescribing physician and received services from a large pharmacy
      provider. Participants were interdisciplinary care teams (physicians, nurses,
      consultant pharmacists, and other staff) who met quarterly. Intervention homes
      participated in three educational meetings over 12 months, including a
      standardized presentation led by expert opinion leaders, action planning for
      quality improvement, and audit and feedback review. Control homes did not receive
      any additional intervention. Resident-level prescribing and clinical outcomes
      were collected from the pharmacy database; data collectors and analysts were
      blinded. In addition to feasibility measures, study outcomes were the proportion
      of residents taking vitamin D (>=800 IU/daily; primary), calcium >=500 mg/day and
      osteoporosis medications (high-risk residents) over 12 months. Data were analyzed
      using the generalized estimating equations technique accounting for clustering
      within the LTC homes. RESULTS: At baseline, 5,478 residents, mean age 84.4
      (standard deviation (SD) 10.9), 71% female, resided in 40 LTC homes, mean size =
      137 beds (SD 76.7). In the intention-to-treat analysis (21 control; 19
      intervention clusters), the intervention resulted in a significantly greater
      increase in prescribing from baseline to 12 months between intervention versus
      control arms for vitamin D (odds ratio (OR) 1.82, 95% confidence interval (CI):
      1.12, 2.96) and calcium (OR 1.33, 95% CI: 1.01, 1.74), but not for osteoporosis
      medications (OR 1.17, 95% CI: 0.91, 1.51). In secondary analyses, excluding seven
      nonparticipating intervention homes, ORs were 3.06 (95% CI: 2.18, 4.29), 1.57
      (95% CI: 1.12, 2.21), 1.20 (95% CI: 0.90, 1.60) for vitamin D, calcium and
      osteoporosis medications, respectively. CONCLUSIONS: Our KT intervention
      significantly improved the prescribing of vitamin D and calcium and is a model
      that could potentially be applied to other areas requiring quality improvement.
      TRIAL REGISTRATION: ClinicalTrials.gov: NCT01398527 . Registered: 19 July 2011.

PMID- 25962888
TI  - Aggressive renal tumour: squamous cell carcinoma with sarcomatoid
      differentiation.

PMID- 25962890
TI  - A prospective Phase 2a pilot study investigating focal percutaneous irreversible
      electroporation (IRE) ablation by NanoKnife in patients with localised renal cell
      carcinoma (RCC) with delayed interval tumour resection (IRENE trial).
AB  - INTRODUCTION: Focal ablation therapy is playing an increasing role in oncology
      and may reduce the toxicity of current surgical treatments while achieving
      adequate oncological benefit. Irreversible electroporation (IRE) has been
      proposed to be tissue-selective with potential advantages compared with current
      thermal-ablation technologies or radiotherapy. The aim of this pilot trial is to
      determine the effectiveness and feasibility of focal percutaneous IRE in patients
      with localised renal cell cancer as a uro-oncological tumour model. METHODS:
      Prospective, monocentric Phase 2a pilot study following current recommendations,
      including those of the International Working Group on Image-Guided Tumor
      Ablation. Twenty patients with kidney tumour (T1aN0M0) will be recruited. This
      sample permits an appropriate evaluation of the feasibility and effectiveness of
      image-guided percutaneous IRE ablation of locally confined kidney tumours as well
      as functional outcomes. Percutaneous biopsy for histopathology will be performed
      before IRE, with magnetic-resonance imaging one day before and 2, 7, 27 and 112
      days after IRE; at 28 days after IRE the tumour region will be completely
      resected and analysed by ultra-thin-layer histology. DISCUSSION: The IRENE study
      will investigate over a short-term observation period (by magnetic-resonance
      imaging, post-resection histology and assessment of technical feasibility)
      whether focal IRE, as a new ablation procedure for soft tissue, is feasible as a
      percutaneous, tissue-sparing method for complete ablation and cure of localised
      kidney tumours. Results from the kidney-tumour model can provide guidance for
      designing an effectiveness and feasibility trial to assess this new ablative
      technology, particularly in uro-oncology.

PMID- 25962889
TI  - An exercise trial targeting African-American women with metabolic syndrome and at
      high risk for breast cancer: Rationale, design, and methods.
AB  - BACKGROUND: Metabolic syndrome and obesity are known risk factors for breast
      cancers. Exercise interventions can potentially modify circulating biomarkers of
      breast cancer risk but evidence in African-Americans and women with metabolic
      syndrome is lacking. METHODS/DESIGN: The Focused Intervention on Exercise to
      Reduce CancEr (FIERCE) trial is a prospective, 6-month, 3-arm, randomized
      controlled trial to examine the effect of exercise on obesity, metabolic syndrome
      components, and breast cancer biomarkers among African-American women at high
      risk of breast cancer. Two hundred-forty inactive women with metabolic syndrome
      and absolute risk of breast cancer >= 1.40 will be randomized to one of the three
      trial arms: 1) a supervised, facility-based exercise arm; 2) a home-based
      exercise arm; and 3) a control group that maintains physical activity levels
      through the course of the trial. Assessments will be conducted at baseline, 3
      months, and 6 months. The primary outcome variables are anthropometric indicators
      of obesity, metabolic syndrome components, and inflammatory, insulin-pathway, and
      hormonal biomarkers of breast cancer risk. DISCUSSION: The FIERCE trial will
      provide evidence on whether a short-term exercise intervention might be effective
      in reducing breast cancer risk among African-American women with comorbidities
      and high breast cancer risk--a group traditionally under-represented in non
      therapeutic breast cancer trials. CLINICAL TRIAL REGISTRATION NUMBER:
      NCT02103140.

PMID- 25962891
TI  - How to Measure Motivational Interviewing Fidelity in Randomized Controlled
      Trials: Practical Recommendations.
AB  - Many randomized controlled trials in which motivational interviewing (MI) is a
      key intervention make no provision for the assessment of treatment fidelity. This
      methodological shortcoming makes it impossible to distinguish between high- and
      low-quality MI interventions, and, consequently, to know whether MI provision has
      contributed to any intervention effects. This article makes some practical
      recommendations for the collection, selection, coding and reporting of MI
      fidelity data, as measured using the Motivational Interviewing Treatment
      Integrity Code. We hope that researchers will consider these recommendations and
      include MI fidelity measures in future studies. 

PMID- 25962892
TI  - Stent Placement for Portal Vein Stenosis After Pancreaticoduodenectomy.
AB  - BACKGROUND: Portal vein (PV) stenosis is a worrisome late complication following
      pancreaticoduodenectomy (PD) that causes intestinal bleeding from varices, which
      must be diagnosed correctly and treated promptly. Recent reports advocate the
      usefulness of stent placement to improve PV stenosis. METHODS: We evaluated the
      cause, diagnosis, and treatment method of PV stenosis after PD and the duration
      of stent patency in our institution. RESULTS: Intestinal bleeding caused by PV
      stenosis occurred in 5 (2.4%) of 205 patients. A computed tomography scan was
      useful to diagnose this complication. Four of 5 patients with PV stenosis
      underwent percutaneous transhepatic PV stent placement. The duration of stent
      patency was 21-41 months, and no rebleeding occurred. CONCLUSIONS: Percutaneous
      stent placement is viable, less invasive option than laparotomy for the
      management of PV stenosis after PD.

PMID- 25962893
TI  - Case Study: Somatic Sprouts and Halo-Like Amorphous Materials of the Purkinje
      Cells in Huntington's Disease.
AB  - We described a 63-year-old Japanese female with genetically confirmed
      Huntington's disease who showed unusual pathological findings in the cerebellum.
      This case exhibited typical neuropathological features as Huntington's disease,
      including severe degeneration of the neostriatum and widespread occurrence of
      ubiquitin and expanded polyglutamine-positive neuronal intranuclear and
      intracytoplasmic inclusions. The cerebellum was macroscopically unremarkable;
      however, somatic sprouts and halo-like amorphous materials of Purkinje cell with
      a large amount of torpedoes were noteworthy. Furthermore, the Purkinje cells were
      found to have granular cytoplasmic inclusions. Somatic sprouting is a form of
      degenerated Purkinje cell exhibited in several specific conditions. Although this
      finding usually appeared in developmental brains, several neurodegenerative
      disorders, including Menkes kinky hair disease, familial spinocerebellar ataxia,
      acute encephalopathy linked to familial hemiplegic migraine, and several other
      conditions, have been reported showing sprouting from the soma of Purkinje cell.
      We propose that Huntington's disease is another degenerative condition associated
      with these distinct neuropathological findings of Purkinje cell. Abnormally
      accumulated huntingtin protein in the cytoplasm could be related to the
      development of these structures. 

PMID- 25962894
TI  - Rapid method for thermal dose-based safety supervision during MR scans.
AB  - To maximize diagnostic accuracy and minimize costs, magnetic resonance imaging
      (MRI) scanners expose patients to electromagnetic exposure levels well above the
      established maximum, but in a well-controlled environment. In this paper, we
      discuss a novel safety assessment model that offers maximum flexibility while
      ensuring no local tissue damage due to radiofrequency induced heating occurs.
      This model is based on the cumulative equivalent minutes at 43  degrees C (CEM43)
      thermal dose concept, which naturally considers exposure duration, tissue
      sensitivity and the transient nature of heating, and permits rapid assessment of
      exposure safety of a given MRI scan using information about the transient
      specific absorption rate (SAR). It builds upon theoretical considerations (e.g.,
      relating peak temperatures in the presence and absence of local thermoregulation)
      as well as data extracted from simulations involving anatomical models (e.g., to
      determine the characteristic time of temperature changes). The model is capable
      of predicting CEM43 for patients with either uncompromised thermoregulation or
      absent thermoregulation. The model predictions approximate detailed simulations
      well and results illustrate the importance of adequately considering changes in
      perfusion. The model presented herein offers an MRI safety assessment approach
      that overcomes problems associated with traditional SAR-based limits. Its
      limitations and the associated uncertainties are discussed together with
      remaining open questions.

PMID- 25962895
TI  - 'I want to feel at home': establishing what aspects of environmental design are
      important to people with dementia nearing the end of life.
AB  - BACKGROUND: The design of environments in which people with dementia live should
      be understandable, reinforce personal identity and maintain their abilities. The
      focus on supporting people with dementia to live well has omitted considering the
      needs or wishes for a supportive physical environment of those who are nearing
      the end of their lives. Using a combination of focus groups and a Delphi survey,
      this study explored the views of people with dementia, family carers and
      professionals on what aspects of the physical environment would be important to
      support a good quality of life to the very end. METHODS: Three focus groups were
      carried out in three cities along the East Coast of Australia using a discussion
      guide informed by a literature review. Focus groups comprised recently bereaved
      family carers of people with dementia (FG1), people with dementia and family
      carers of people with dementia (FG2) and practitioners caring for people with
      dementia nearing or at the end of their lives (FG3). Focus group conversations
      were audio-recorded with participants' consent. Audio files were transcribed
      verbatim and analysed thematically to identify environmental features that could
      contribute to achieving the goal of providing a comfortable life to the end. A
      list of design features derived from analysis of focus group transcripts was
      distributed to a range of experts in the dementia field and a consensus sought on
      their appropriateness. From this, a set of features to inform the design of
      environments for people with dementia nearing the end of life was defined.
      RESULTS: Eighteen people took part in three focus groups: two with dementia,
      eleven current or recently bereaved family carers and five practitioners. There
      were differences in opinion on what were important environmental considerations.
      People with dementia and family carers identified comfort through engagement,
      feeling at home, a calm environment, privacy and dignity and use of technology to
      remain connected as important. For practitioners, design to facilitate duty of
      care and institutional influences on their practice were salient themes. Twenty
      one experts in the dementia field took part in the survey to agree a consensus on
      the desirable features derived from analysis of focus group transcripts, with
      fifteen features agreed. CONCLUSIONS: The fifteen features are compatible with
      the design principles for people with dementia who are mobile, but include a
      stronger focus on sensory engagement. We suggest that considering these features
      as part of a continuum of care will support good practice and offer those with
      dementia the opportunity to live well until the end and give their families a
      more positive experience in the last days of their lives together.

PMID- 25962896
TI  - Sarcopenia--The search for emerging biomarkers.
AB  - Sarcopenia, an age-related decline in skeletal muscle mass and function,
      dramatically affects the life quality of elder people. In view of increasing life
      expectancy, sarcopenia renders a heavy burden on the health care system. However,
      although there is a consensus that sarcopenia is a multifactorial syndrome, its
      etiology, underlying mechanisms, and even definition remain poorly delineated,
      thus, preventing development of a precise treatment strategy. The main aim of our
      review is to critically analyze potential sarcopenia biomarkers in light of the
      molecular mechanisms of their involvement in sarcopenia pathogenesis. Normal
      muscle mass and function maintenance are proposed to be dependent on the dynamic
      balance between the positive regulators of muscle growth such as bone
      morphogenetic proteins (BMPs), brain-derived neurotrophic factor (BDNF),
      follistatin (FST) and irisin, and negative regulators including TGFbeta,
      myostatin, activins A and B, and growth and differentiation factor-15 (GDF-15).
      We hypothesize that the shift in this balance to muscle growth inhibitors, along
      with increased expression of the C- terminal agrin fragment (CAF) associated with
      age-dependent neuromuscular junction (NMJ) dysfunction, as well as skeletal
      muscle-specific troponin T (sTnT), a key component of contractile machinery, is a
      main mechanism underlying sarcopenia pathogenesis. Thus, this review proposes and
      emphasizes that these molecules are the emerging sarcopenia biomarkers. 

PMID- 25962897
TI  - An excellent result of surgical treatment in patients with severe pulmonary
      arterial hypertension following mitral valve disease.
AB  - OBJECTIVE: Observe the efficacy of surgical treatment in patients with severe
      pulmonary arterial hypertension caused by mitral valve disease. METHODS: We
      examined the results of surgical treatment in 32 patients with mitral valve
      disease and severe pulmonary arterial hypertension (pulmonary arterial systolic
      pressure >= 80 mmHg) retrospectively. Operative and postoperative data collection
      included type of the surgery, cardiopulmonary bypass time, cross-clamp time and
      the mortality rate. Pulmonary arterial systolic pressure, left atrial diameter,
      left ventricular end-diastolic diameter, and left ventricular ejection fraction
      were recorded and compared. RESULTS: A total number of 32 patients had the
      operation of mitral valve replacement. Among those subjects, twenty-seven
      patients were surgically replaced with mechanical prosthesis and five patients
      with tissue prosthesis. Only one patient died of pneumonia, with a mortality rate
      of 3.1 %. The statistical results of preoperative and postoperative
      echocardiographic data showed significant decrease in pulmonary arterial systolic
      pressure (101.2 +/- 20.3 versus 48.1 +/- 14.3 mmHg, P < 0.05), left atrial
      diameter(67.6 +/- 15.7 versus 54.4 +/- 11.4 mm, P < 0.05) and left ventricular
      end-diastolic diameter (52.3 +/- 9.5 versus 49.2 +/- 5.9 mm, P < 0.05). There was
      no significant change in left ventricular ejection fraction (59.2 +/- 6.5 versus
      57.9 +/- 7.6, P = NS). At the time of follow-up, twenty-eight (96.6 %) patients
      were classified in New York Heart Association functional class I or II, one(3.4
      %) in class III, with the mortality rate is zero percent. CONCLUSIONS: Mitral
      valve replacement can be performed successfully in patients with mitral valve
      disease and severe pulmonary arterial hypertension with an acceptable
      perioperative risk.

PMID- 25962898
TI  - Establishment and characterization of a cell line from human adenoid cystic
      carcinoma of the lacrimal glands and a nude mouse transplantable model.
AB  - Using tissue block culture techniques, we established a new human tumor cell line
      derived from adenoid cystic carcinoma of the lacrimal glands (LACC-1). The LACC-1
      cell line was successfully subcultured for more than 100 passages during the last
      two years. The outgrowth of cells was observed by day 5 after seeding, and then
      the cells were generated slowly. The first passage proceeded by day 32, and the
      classical epithelioid cell colonies formed by day 69 after inoculation. After
      eight passages, homogeneous epithelioid tumor cells appeared when we combined
      continuous passage, mechanical scraping, repeated adherence, and dissociation
      methods to remove the fibroblast cells. LACC-1 cells appeared as a histologically
      solid pattern and continuous passage culture. The population doubling time was
      approximately 37.1 h. LACC-1 cells appeared as an epithelioid monolayer culture
      on the cell culture flask and presented with a cobblestone-like appearance when
      they reached confluency. The nucleus was large and round with many abnormal
      mitoses. The nucleoplasm ratio was high. Multinucleated tumor giant cells
      appeared. LACC-1 cells showed a tendency to have overlapping growth without
      contact inhibition when the cell density continued to increase. Scanning electron
      microscopy (SEM) and transmission electron microscopy (TEM) showed that the LACC
      1 cells were malignant tumor cells that were poorly differentiated. The surface
      of the LACC-1 cells exhibited affluent microvilli, protuberances and filopodia
      under SEM. The no. 84 generation LACC-1 cell line was inoculated subcutaneously
      into the subaxillary of nude mice and the tumorigenic potential was evident. The
      formation rate of the transplanted tumors was 100% at day 7 after inoculation.
      This finding showed that the LACC-1 cell line was malignant with tumorigenic
      ability. The xenograft tumors retained the same histological characteristics of a
      solid pattern as the LACC-1 original tumor after inoculation for 49 days. Under
      TEM observation, the xenograft tumor cells had the same ultrastructure as the
      LACC-1 cells. Immunohistochemical examination revealed the similarity of both
      cytoskeletal proteins (e.g., cytokeratin, vimentin, desmin and alpha-SMA) and S
      100 expression in the original tumor, LACC-1 cells and xenograft tumors.
      Immunoreactivity of these proteins was gradually decreased in these three
      tissues. Reverse transcription-polymerase chain reaction demonstrated that the
      xenograft tumors originated from the human. Based on these results, the LACC-1
      cell line provides a useful model for studying the biological characteristics of
      human ACC of the lacrimal glands.

PMID- 25962899
TI  - A male patient with acromegaly and breast cancer: treating acromegaly to control
      tumor progression.
AB  - BACKGROUND: Acromegaly is a rare disease associated with an increased risk of
      developing cancer. CASE PRESENTATION: We report the case of a 72-year-old man who
      was diagnosed with acromegaly (IGF-1 770 ng/ml) and breast cancer. Four years
      before he suffered from a colon-rectal cancer. Pituitary surgery and octreotide
      LAR treatment failed to control acromegaly. Normalization of IGF-1 (97 ng/ml) was
      obtained with pegvisomant therapy. Four years after breast cancer surgery, 2
      pulmonary metastases were detected at chest CT. The patient was started on
      anastrozole, but, contrary to medical advice, he stopped pegvisomant treatment
      (IGF-I 453 ng/ml). Four months later, chest CT revealed an increase in size of
      the metastatic lesion of the left lung. The patient was shifted from anastrozole
      to tamoxifen and was restarted on pegvisomant, with normalization of serum IGF-1
      levels (90 ng/ml). Four months later, a reduction in size of the metastatic
      lesion of the left lung was detected by CT. Subsequent CT scans throughout a 24
      month follow-up showed a further reduction in size and then a stabilization of
      the metastasis. CONCLUSIONS: This is the first report of a male patient with
      acromegaly and breast cancer. The clinical course of breast cancer was closely
      related to the metabolic control of acromegaly. The rapid progression of
      metastatic lesion was temporally related to stopping pegvisomant treatment and
      paralleled a rise in serum IGF-1 levels. Normalization of IGF-1 after re-starting
      pegvisomant impressively reduced the progression of metastatic breast lesions.
      Control of acromegaly is mandatory in acromegalic patients with cancer.

PMID- 25962900
TI  - Evolution pathways of IgE responses to grass and mite allergens throughout
      childhood.
AB  - BACKGROUND: Little is known about longitudinal patterns of the development of IgE
      to distinct allergen components. OBJECTIVE: We sought to investigate the
      evolution of IgE responses to allergenic components of timothy grass and dust
      mite during childhood. METHODS: In a population-based birth cohort (n = 1184) we
      measured IgE responses to 15 components from timothy grass and dust mite in
      children with available samples at 3 time points (ages 5, 8, and 11 years; n =
      235). We designed a nested, 2-stage latent class analysis to identify cross
      sectional sensitization patterns at each follow-up and their longitudinal
      trajectories. We then ascertained the association of longitudinal trajectories
      with asthma, rhinitis, eczema, and lung function in children with component data
      for at least 2 time points (n = 534). RESULTS: Longitudinal latent class analysis
      revealed 3 grass sensitization trajectories: (1) no/low sensitization; (2) early
      onset; and (3) late onset. The early-onset trajectory was associated with asthma
      and diminished lung function, and the late-onset trajectory was associated with
      rhinitis. Four longitudinal trajectories emerged for mite: (1) no/low
      sensitization; (2) group 1 allergens; (3) group 2 allergens; and (3) complete
      mite sensitization. Children in the complete mite sensitization trajectory had
      the highest odds ratios (ORs) for asthma (OR, 7.15; 95% CI, 3.80-13.44) and were
      the only group significantly associated with comorbid asthma, rhinitis, and
      eczema (OR, 5.91; 95% CI, 2.01-17.37). Among children with wheezing, those in the
      complete mite sensitization trajectory (but not other longitudinal mite
      trajectories) had significantly higher risk of severe exacerbations (OR, 3.39;
      95% CI, 1.62-6.67). CONCLUSIONS: The nature of developmental longitudinal
      trajectories of IgE responses differed between grass and mite allergen
      components, with temporal differences (early vs late onset) dominant in grass and
      diverging patterns of IgE responses (group 1 allergens, group 2 allergens, or
      both) in mite. Different longitudinal patterns bear different associations with
      clinical outcomes, which varied by allergen.

PMID- 25962901
TI  - Thymic stromal lymphopoietin activation of basophils in patients with allergic
      asthma is IL-3 dependent.
AB  - BACKGROUND: Thymic stromal lymphopoietin (TSLP) released after antigenic
      stimulation of allergic asthmatic airways is a key initiator of type 2
      inflammation. Basophils are important effectors of allergic inflammation in the
      airways. Murine basophils have been shown to respond to TSLP independently of IL
      3 by increasing functional thymic stromal lymphopoietin receptor (TSLPR)
      expression. OBJECTIVE: The purpose of this study was to investigate the effect of
      TSLP stimulation on human basophil function. METHODS: Ten patients with mild
      allergic asthma underwent diluent and allergen inhalation challenges. Peripheral
      blood and sputum samples were collected at baseline and 7 and 24 hours after
      challenge, and bone marrow samples were collected at baseline and 24 hours after
      challenge to measure basophil TSLPR expression. In vitro experiments were
      conducted on purified human basophils to measure the effect of TSLP on
      degranulation, expression of activation markers and TH2 cytokines, and eotaxin
      induced shape change. RESULTS: Allergen inhalation increased basophil numbers in
      the airways and significantly upregulated the expression of activation markers,
      TH2 intracellular cytokines, and receptors for TSLP, IL-3, and eotaxin in blood,
      bone marrow, and sputum basophils. In vitro stimulation with TSLP primed basophil
      migration to eotaxin and induced rapid and sustained basophil activation mediated
      directly through TSLPR and indirectly through an IL-3-mediated basophil autocrine
      loop. Basophils responded to TSLP at a similar magnitude and potency as the well
      described basophil-activating stimuli IL-3 and anti-IgE. CONCLUSION: Our findings
      indicate that basophil activation during early- and late-phase responses to
      inhaled allergen might be driven at least in part by TSLP.

PMID- 25962904
TI  - National summit on advanced illness care.

PMID- 25962902
TI  - Skin dendritic cells induce follicular helper T cells and protective humoral
      immune responses.
AB  - BACKGROUND: The contribution of individual subsets of dendritic cells (DCs) to
      generation of adaptive immunity is central to understanding immune homeostasis
      and protective immune responses. OBJECTIVE: We sought to define functions for
      steady-state skin DCs. METHODS: We present an approach in which we restrict
      antigen presentation to individual DC subsets in the skin and monitor the effects
      on endogenous antigen-specific CD4(+) T- and B-cell responses. RESULTS:
      Presentation of foreign antigen by Langerhans cells (LC) in the absence of
      exogenous adjuvant led to a large expansion of T follicular helper (TFH) cells.
      This was accompanied by B-cell activation, germinal center formation, and
      protective antibody responses against influenza. The expansion of TFH cells and
      antibody responses could be elicited by both systemic and topical skin
      immunization. TFH cell induction was not restricted to LCs and occurred in
      response to antigen presentation by CD103(+) dermal DCs. CD103(+) DCs, despite
      inducing similar TFH responses as LCs, were less efficient in induction of
      germinal center B cells and humoral immune responses. We also found that skin DCs
      are sufficient to expand CXCR5(+) TFH cells through an IL-6- and IFN-alpha/beta
      receptor-independent mechanism, but B cells were required for sustained Bcl-6(+)
      expression. CONCLUSIONS: These data demonstrate that a major unappreciated
      function of skin DCs is their promotion of TFH cells and humoral immune responses
      that potentially represent an efficient approach for vaccination.

PMID- 25962903
TI  - Prostaglandin E2 inhibits mast cell-dependent bronchoconstriction in human small
      airways through the E prostanoid subtype 2 receptor.
AB  - BACKGROUND: Inhaled prostaglandin (PG) E2 might inhibit asthmatic responses, but
      the mechanisms involved remain undefined. OBJECTIVE: We sought to characterize
      the direct and indirect effects of PGE2 on human small airways with particular
      reference to the receptors mediating the responses. METHODS: Contraction and
      relaxation were studied in isolated human bronchi with an inner diameter of 1 mm
      or less. RESULTS: Low concentrations of PGE2 (0.01-1 MUmol/L) relaxed the bronchi
      precontracted by histamine. The bronchodilator response was inhibited by the E
      prostanoid (EP) subtype 4 receptor antagonist ONO-AE3-208 but unaffected by the
      EP2 receptor antagonist PF-04418948. Higher concentrations of PGE2 (10-100
      MUmol/L) contracted the small airways. However, the TP receptor agonists U
      46,619, PGF2alpha, and PGD2 were more potent than PGE2. Moreover, the
      bronchoconstrictor responses to PGE2 and all other tested prostanoids, including
      the EP1/EP3 receptor agonist 17-phenyl trinor PGE2 and the partial FP receptor
      agonist AL-8810, were uniformly abolished by the TP receptor antagonist SQ
      29,548. In the presence of TP and EP4 antagonists, PGE2 inhibited the mast cell
      mediated bronchoconstriction resulting from anti-IgE challenge. Measurement of
      the release of histamine and cysteinyl leukotrienes documented that this
      bronchoprotective action of PGE2 was mediated by the EP2 receptor, unrelated to
      bronchodilation, and increased with time of exposure. CONCLUSION: The
      pharmacology of PGE2 in isolated human small airways was different from its
      profile in animal models. This first demonstration of powerful EP2 receptor
      mediated inhibition of IgE-dependent contractions in human airways introduces a
      new selective target for the treatment of asthma. This EP2 control of mast cell
      mediated bronchoconstriction is presumably exaggerated in patients with aspirin
      exacerbated respiratory disease.

PMID- 25962905
TI  - Workplace formative assessment: faculty members' beliefs.
AB  - BACKGROUND: Workplace-based formative assessment (WFA) is an increasingly used
      tool in graduate medical education as it serves to evaluate and teach; however,
      the use of WFA is reportedly low. The objectives of this study were to assess the
      proportion of dermatology residency training programmes using WFA, and to
      describe faculty members' beliefs about the factors that support or impede its
      use. METHODS: An electronic survey was distributed to all US dermatology
      programmes. RESULTS: Responses were collected from 43 per cent (56/131) of the US
      dermatology programmes. Half (28/56) of the respondent programmes use WFA. The
      most frequently endorsed advantage was 'provides feedback to residents about
      their performance'. The most frequent barriers were 'time for faculty to observe'
      and 'faculty interest'. DISCUSSION: WFA has been shown to stimulate learning
      through the exchange of feedback with a learner about gaps in his or her
      practice. This study showed that WFA is not yet used in the majority of
      dermatology training programmes. Time for faculty members to perform WFA was the
      most cited barrier to the use of WFA, but few studies have investigated the
      actual time requirement. Secondly, faculty members' interest may be encouraged
      through training and an increased awareness of the impact of WFA. For example,
      the evidence supporting the effects of feedback include a meta-analysis of over
      1800 studies showed that the effect of feedback, especially regarding performance
      on a specific task, was greater than the effect of schooling.

PMID- 25962906
TI  - Performance of the Afirma Gene Expression Classifier in Hurthle Cell Thyroid
      Nodules Differs from Other Indeterminate Thyroid Nodules.
AB  - BACKGROUND: The recently introduced Afirma gene expression classifier (AGEC)
      provides binary results (benign or suspicious) to guide management of
      cytologically indeterminate thyroid nodules. The AGEC is intended to reduce
      unnecessary surgeries for benign nodules, and management algorithms favor surgery
      for suspicious results. Limited data are available on the performance of this
      test for Hurthle cell nodules (HCNs). This study hypothesized that a predominance
      of Hurthle cells leads to an increased rate of suspicious AGEC results with a
      potential for overtreatment, despite a relatively low risk of malignancy.
      METHODS: The pathology databases from three tertiary care facilities were queried
      from 2010 to 2014 for fine-needle aspirates (FNAs) diagnosed as suspicious for
      Hurthle cell neoplasm (SHCN) or atypia of undetermined significance/follicular
      lesion of undetermined significance concerning for Hurthle cell neoplasm (AFHCN).
      Cytology diagnoses were rendered internally prior to AGEC testing. The patient
      demographics, FNA diagnosis, AGEC result, surgical procedure, and pathologic
      outcomes were recorded. RESULTS: The cohort consisted of 134 patients with HCNs.
      Prior to AGEC availability, 62 patients underwent surgery: 81% (50/62) of
      patients had surgery, and 34% (17/50) of the resected index nodules were
      malignant. After introduction of the AGEC, 72 patients underwent AGEC testing:
      65% (47/72) of patients had surgery, and 13% (6/46) of the resected nodules were
      malignant. Thirty-two percent (23/72) of patients had a benign AGEC result and
      did not undergo surgery, and 4% (3/72) had surgery despite a benign AGEC result
      with benign final pathology, whereas 63% (45/72) of patients had suspicious AGEC
      results, with 96% of these patients (43/45) undergoing surgery, and 14% (6/43) of
      these index nodules were malignant. CONCLUSIONS: While 32% of tested patients
      declined surgery based on a benign AGEC, 86% of patients with suspicious AGEC
      findings had unnecessary surgery, reflecting a substantially lower rate of
      malignancy from what was previously reported for all indeterminate nodules. Given
      the approximate pretest malignancy risk of 25-35% for an FNA diagnosis of SHCN or
      AFHCN, a suspicious AGEC diagnosis does not increase the probability of
      malignancy in an HCN, and patients should be counseled accordingly.

PMID- 25962907
TI  - Comparison of doses received by the hippocampus in patients treated with single
      isocenter- vs multiple isocenter-based stereotactic radiation therapy to the
      brain for multiple brain metastases.
AB  - To investigate the doses received by the hippocampus and normal brain tissue
      during a course of stereotactic radiation therapy using a single isocenter (SI)
      based or multiple isocenter (MI)-based treatment planning in patients with less
      than 4 brain metastases. In total, 10 patients with magnetic resonance imaging
      (MRI) demonstrating 2-3 brain metastases were included in this retrospective
      study, and 2 sets of stereotactic intensity-modulated radiation therapy (IMRT)
      treatment plans (SI vs MI) were generated. The hippocampus was contoured on SPGR
      sequences, and doses received by the hippocampus and the brain were calculated
      and compared between the 2 treatment techniques. A total of 23 lesions in 10
      patients were evaluated. The median tumor volume, the right hippocampus volume,
      and the left hippocampus volume were 3.15, 3.24, and 2.63mL, respectively. In
      comparing the 2 treatment plans, there was no difference in the planning target
      volume (PTV) coverage except in the tail for the dose-volume histogram (DVH)
      curve. The only statistically significant dosimetric parameter was the V100. All
      of the other measured dosimetric parameters including the V95, V99, and D100 were
      not significantly different between the 2 treatment planning techniques. None of
      the dosimetric parameters evaluated for the hippocampus revealed any
      statistically significant difference between the MI and SI plans. The total brain
      doses were slightly higher in the SI plans, especially in the lower dose region,
      although this difference was not statistically different. The use of SI-based
      treatment plan resulted in a 35% reduction in beam-on time. The use of SI
      treatments for patients with up to 3 brain metastases produces similar PTV
      coverage and similar normal tissue doses to the hippocampus and the brain when
      compared with MI plans. SI treatment planning should be considered in patients
      with multiple brain metastases undergoing stereotactic treatment. 

PMID- 25962908
TI  - Medical examiner and coroner reports: uses and limitations in the epidemiology
      and prevention of late-life suicide.
AB  - OBJECTIVE: Late-life suicide is a growing public health concern in many parts of
      the world. Understanding the contributory factors to completed suicide is
      essential to inform the development of effective suicide risk assessment and
      management. The aim of this study is to synthesise the findings in studies that
      used coroner or medical examiner records to determine these contributory factors.
      METHODS: The databases of Scopus (from 1960), MEDLINE (from 1946) and PsychINFO
      (from 1806) were searched in August 2013, to identify studies that used coroner
      or medical examiner records for investigating the epidemiological,
      sociodemographic characteristics and clinical aspects of late-life suicide.
      RESULTS: In total, 25 studies were identified. There was a lack of
      standardisation of variables assessed between studies leading to incomplete
      datasets in some work. However, a diagnosis of depression was found in 33%, and
      depressive mood/symptoms in 47% of cases. About 55% had a physical health
      problem. Terminal illness was associated with a smaller proportion (7.1%) of the
      cases. Older people were more likely to have had contact with primary care rather
      than mental health services prior to suicide. CONCLUSIONS: Despite their
      limitations, coroner and medical examiner records provide an opportunity for
      examining suicide epidemiology. Targeting primary care providers where late-life
      depression and physical illness can be detected and treated is a potential
      strategy to address late-life suicide.

PMID- 25962910
TI  - Cell biology of the NCL proteins: What they do and don't do.
AB  - The fatal, primarily childhood neurodegenerative disorders, neuronal ceroid
      lipofuscinoses (NCLs), are currently associated with mutations in 13 genes. The
      protein products of these genes (CLN1 to CLN14) differ in their function and
      their intracellular localization. NCL-associated proteins have been localized
      mostly in lysosomes (CLN1, CLN2, CLN3, CLN5, CLN7, CLN10, CLN12 and CLN13) but
      also in the Endoplasmic Reticulum (CLN6 and CLN8), or in the cytosol associated
      to vesicular membranes (CLN4 and CLN14). Some of them such as CLN1 (palmitoyl
      protein thioesterase 1), CLN2 (tripeptidyl-peptidase 1), CLN5, CLN10 (cathepsin
      D), and CLN13 (cathepsin F), are lysosomal soluble proteins; others like CLN3,
      CLN7, and CLN12, have been proposed to be lysosomal transmembrane proteins. In
      this review, we give our views and attempt to summarize the proposed and
      confirmed functions of each NCL protein and describe and discuss research results
      published since the last review on NCL proteins. This article is part of a
      Special Issue entitled: "Current Research on the Neuronal Ceroid Lipofuscinoses
      (Batten Disease)". 

PMID- 25962911
TI  - Role of DNA Methylation on the Expression of the Anthracycline Metabolizing
      Enzyme AKR7A2 in Human Heart.
AB  - The intracardiac synthesis of anthracycline alcohol metabolites by aldo-keto
      reductases (AKRs) contributes to the pathogenesis of anthracycline-related
      cardiotoxicity. AKR7A2 is the most abundant anthracycline reductase in hearts
      from donors with and without Down syndrome (DS), and its expression varies
      between individuals (~tenfold). We investigated whether DNA methylation impacts
      AKR7A2 expression in hearts from donors with (n = 11) and without DS (n = 30).
      Linear models were used to test for associations between methylation status and
      cardiac AKR7A2 expression. In hearts from donors without DS, DNA methylation
      status at CpG site -865 correlated with AKR7A2 mRNA (Pearson's regression
      coefficient, r = -0.4051, P = 0.0264) and AKR7A2 protein expression (r = -0.5818,
      P = 0.0071). In heart tissue from donors with DS, DNA methylation status at CpG
      site -232 correlated with AKR7A2 protein expression (r = 0.8659, P = 0.0025).
      Multiple linear regression modeling revealed that methylation at several CpG
      sites is associated with the synthesis of cardiotoxic daunorubicinol. AKR7A2
      methylation status in lymphoblastoid cell lines from donors with and without DS
      was examined to explore potential parallelisms between cardiac tissue and
      lymphoid cells. These results suggest that DNA methylation impacts AKR7A2
      expression and the synthesis of cardiotoxic daunorubicinol. 

PMID- 25962912
TI  - Induction of the Nitrate Assimilation nirA Operon and Protein-Protein
      Interactions in the Maturation of Nitrate and Nitrite Reductases in the
      Cyanobacterium Anabaena sp. Strain PCC 7120.
AB  - Nitrate is widely used as a nitrogen source by cyanobacteria, in which the
      nitrate assimilation structural genes frequently constitute the so-called nirA
      operon. This operon contains the genes encoding nitrite reductase (nirA), a
      nitrate/nitrite transporter (frequently an ABC-type transporter; nrtABCD), and
      nitrate reductase (narB). In the model filamentous cyanobacterium Anabaena sp.
      strain PCC 7120, which can fix N2 in specialized cells termed heterocysts, the
      nirA operon is expressed at high levels only in media containing nitrate or
      nitrite and lacking ammonium, a preferred nitrogen source. Here we examined the
      genes downstream of the nirA operon in Anabaena and found that a small open
      reading frame of unknown function, alr0613, can be cotranscribed with the operon.
      The next gene in the genome, alr0614 (narM), showed an expression pattern similar
      to that of the nirA operon, implying correlated expression of narM and the
      operon. A mutant of narM with an insertion mutation failed to produce nitrate
      reductase activity, consistent with the idea that NarM is required for the
      maturation of NarB. Both narM and narB mutants were impaired in the nitrate
      dependent induction of the nirA operon, suggesting that nitrite is an inducer of
      the operon in Anabaena. It has previously been shown that the nitrite reductase
      protein NirA requires NirB, a protein likely involved in protein-protein
      interactions, to attain maximum activity. Bacterial two-hybrid analysis confirmed
      possible NirA-NirB and NarB-NarM interactions, suggesting that the development of
      both nitrite reductase and nitrate reductase activities in cyanobacteria involves
      physical interaction of the corresponding enzymes with their cognate partners,
      NirB and NarM, respectively. IMPORTANCE: Nitrate is an important source of
      nitrogen for many microorganisms that is utilized through the nitrate
      assimilation system, which includes nitrate/nitrite membrane transporters and the
      nitrate and nitrite reductases. Many cyanobacteria assimilate nitrate, but
      regulation of the nitrate assimilation system varies in different cyanobacterial
      groups. In the N2-fixing, heterocyst-forming cyanobacteria, the nirA operon,
      which includes the structural genes for the nitrate assimilation system, is
      expressed in the presence of nitrate or nitrite if ammonium is not available to
      the cells. Here we studied the genes required for production of an active nitrate
      reductase, providing information on the nitrate-dependent induction of the
      operon, and found evidence for possible protein-protein interactions in the
      maturation of nitrate reductase and nitrite reductase.

PMID- 25962909
TI  - Current gene therapy using viral vectors for chronic pain.
AB  - The complexity of chronic pain and the challenges of pharmacotherapy highlight
      the importance of development of new approaches to pain management. Gene therapy
      approaches may be complementary to pharmacotherapy for several advantages. Gene
      therapy strategies may target specific chronic pain mechanisms in a tissue
      specific manner. The present collection of articles features distinct gene
      therapy approaches targeting specific mechanisms identified as important in the
      specific pain conditions. Dr. Fairbanks group describes commonly used gene
      therapeutics (herpes simplex viral vector (HSV) and adeno-associated viral vector
      (AAV)), and addresses biodistribution and potential neurotoxicity in pre-clinical
      models of vector delivery. Dr. Tao group addresses that downregulation of a
      voltage-gated potassium channel (Kv1.2) contributes to the maintenance of
      neuropathic pain. Alleviation of chronic pain through restoring Kv1.2 expression
      in sensory neurons is presented in this review. Drs Goins and Kinchington group
      describes a strategy to use the replication defective HSV vector to deliver two
      different gene products (enkephalin and TNF soluble receptor) for the treatment
      of post-herpetic neuralgia. Dr. Hao group addresses the observation that the pro
      inflammatory cytokines are an important shared mechanism underlying both
      neuropathic pain and the development of opioid analgesic tolerance and
      withdrawal. The use of gene therapy strategies to enhance expression of the anti
      pro-inflammatory cytokines is summarized. Development of multiple gene therapy
      strategies may have the benefit of targeting specific pathologies associated with
      distinct chronic pain conditions (by Guest Editors, Drs. C. Fairbanks and S.
      Hao). 

PMID- 25962913
TI  - In Salmonella enterica, Ethanolamine Utilization Is Repressed by 1,2-Propanediol
      To Prevent Detrimental Mixing of Components of Two Different Bacterial
      Microcompartments.
AB  - Bacterial microcompartments (MCPs) are a diverse family of protein-based
      organelles composed of metabolic enzymes encapsulated within a protein shell. The
      function of bacterial MCPs is to optimize metabolic pathways by confining toxic
      and/or volatile metabolic intermediates. About 20% of bacteria produce MCPs, and
      there are at least seven different types. Different MCPs vary in their
      encapsulated enzymes, but all have outer shells composed of highly conserved
      proteins containing bacterial microcompartment domains. Many organisms have genes
      encoding more than one type of MCP, but given the high homology among shell
      proteins, it is uncertain whether multiple MCPs can be functionally expressed in
      the same cell at the same time. In these studies, we examine the regulation of
      the 1,2-propanediol (1,2-PD) utilization (Pdu) and ethanolamine utilization (Eut)
      MCPs in Salmonella. Studies showed that 1,2-PD (shown to induce the Pdu MCP)
      represses transcription of the Eut MCP and that the PocR regulatory protein is
      required. The results indicate that repression of the Eut MCP by 1,2-PD is needed
      to prevent detrimental mixing of shell proteins from the Eut and Pdu MCPs.
      Coexpression of both MCPs impaired the function of the Pdu MCP and resulted in
      the formation of hybrid MCPs composed of Eut and Pdu MCP components. We also show
      that plasmid-based expression of individual shell proteins from the Eut MCP or
      the beta-carboxysome impaired the function of Pdu MCP. Thus, the high
      conservation among bacterial microcompartment (BMC) domain shell proteins is
      problematic for coexpression of the Eut and Pdu MCPs and perhaps other MCPs as
      well. IMPORTANCE: Bacterial MCPs are encoded by nearly 20% of bacterial genomes,
      and almost 40% of those genomes contain multiple MCP gene clusters. In this
      study, we examine how the regulation of two different MCP systems (Eut and Pdu)
      is integrated in Salmonella. Our findings indicate that 1,2-PD (shown to induce
      the Pdu MCP) represses the Eut MCP to prevent detrimental mixing of Eut and Pdu
      shell proteins. These findings suggest that numerous organisms which produce more
      than one type of MCP likely need some mechanism to prevent aberrant shell protein
      interactions.

PMID- 25962914
TI  - Immunogold Localization of Key Metabolic Enzymes in the Anammoxosome and on the
      Tubule-Like Structures of Kuenenia stuttgartiensis.
AB  - Anaerobic ammonium-oxidizing (anammox) bacteria oxidize ammonium with nitrite as
      the terminal electron acceptor to form dinitrogen gas in the absence of oxygen.
      Anammox bacteria have a compartmentalized cell plan with a central membrane-bound
      "prokaryotic organelle" called the anammoxosome. The anammoxosome occupies most
      of the cell volume, has a curved membrane, and contains conspicuous tubule-like
      structures of unknown identity and function. It was suggested previously that the
      catalytic reactions of the anammox pathway occur in the anammoxosome, and that
      proton motive force was established across its membrane. Here, we used antibodies
      raised against five key enzymes of the anammox catabolism to determine their
      cellular location. The antibodies were raised against purified native
      hydroxylamine oxidoreductase-like protein kustc0458 with its redox partner
      kustc0457, hydrazine dehydrogenase (HDH; kustc0694), hydroxylamine oxidase (HOX;
      kustc1061), nitrite oxidoreductase (NXR; kustd1700/03/04), and hydrazine synthase
      (HZS; kuste2859-61) of the anammox bacterium Kuenenia stuttgartiensis. We
      determined that all five protein complexes were exclusively located inside the
      anammoxosome matrix. Four of the protein complexes did not appear to form higher
      order protein organizations. However, the present data indicated for the first
      time that NXR is part of the tubule-like structures, which may stretch the whole
      length of the anammoxosome. These findings support the anammoxosome as the locus
      of catabolic reactions of the anammox pathway. IMPORTANCE: Anammox bacteria are
      environmentally relevant microorganisms that contribute significantly to the
      release of fixed nitrogen in nature. Furthermore, the anammox process is applied
      for nitrogen removal from wastewater as an environment-friendly and cost
      effective technology. These microorganisms feature a unique cellular organelle,
      the anammoxosome, which was proposed to contain the energy metabolism of the cell
      and tubule-like structures with hitherto unknown function. Here, we purified five
      native enzymes catalyzing key reactions in the anammox metabolism and raised
      antibodies against these in order to localize them within the cell. We showed
      that all enzymes were located within the anammoxosome, and nitrite oxidoreductase
      was located exclusively at the tubule-like structures, providing the first
      insights into the function of these subcellular structures.

PMID- 25962915
TI  - Gene Transfer Efficiency in Gonococcal Biofilms: Role of Biofilm Age,
      Architecture, and Pilin Antigenic Variation.
AB  - Extracellular DNA is an important structural component of many bacterial
      biofilms. It is unknown, however, to which extent external DNA is used to
      transfer genes by means of transformation. Here, we quantified the acquisition of
      multidrug resistance and visualized its spread under selective and nonselective
      conditions in biofilms formed by Neisseria gonorrhoeae. The density and
      architecture of the biofilms were controlled by microstructuring the substratum
      for bacterial adhesion. Horizontal transfer of antibiotic resistance genes
      between cocultured strains, each carrying a single resistance, occurred
      efficiently in early biofilms. The efficiency of gene transfer was higher in
      early biofilms than between planktonic cells. It was strongly reduced after 24 h
      and independent of biofilm density. Pilin antigenic variation caused a high
      fraction of nonpiliated bacteria but was not responsible for the reduced gene
      transfer at later stages. When selective pressure was applied to dense biofilms
      using antibiotics at their MIC, the double-resistant bacteria did not show a
      significant growth advantage. In loosely connected biofilms, the spreading of
      double-resistant clones was prominent. We conclude that multidrug resistance
      readily develops in early gonococcal biofilms through horizontal gene transfer.
      However, selection and spreading of the multiresistant clones are heavily
      suppressed in dense biofilms. IMPORTANCE: Biofilms are considered ideal reaction
      chambers for horizontal gene transfer and development of multidrug resistances.
      The rate at which genes are exchanged within biofilms is unknown. Here, we
      quantified the acquisition of double-drug resistance by gene transfer between
      gonococci with single resistances. At early biofilm stages, the transfer
      efficiency was higher than for planktonic cells but then decreased with biofilm
      age. The surface topography affected the architecture of the biofilm. While the
      efficiency of gene transfer was independent of the architecture, spreading of
      double-resistant bacteria under selective conditions was strongly enhanced in
      loose biofilms. We propose that while biofilms help generating multiresistant
      strains, selection takes place mostly after dispersal from the biofilm.

PMID- 25962916
TI  - Importance of Real-Time Assays To Distinguish Multidrug Efflux Pump-Inhibiting
      and Outer Membrane-Destabilizing Activities in Escherichia coli.
AB  - The constitutively expressed AcrAB multidrug efflux system of Escherichia coli
      shows a high degree of homology with the normally silent AcrEF system. Exposure
      of a strain with acrAB deleted to antibiotic selection pressure frequently leads
      to the insertion sequence-mediated activation of the homologous AcrEF system. In
      this study, we used strains constitutively expressing either AcrAB or AcrEF from
      their normal chromosomal locations to resolve a controversy about whether
      phenylalanylarginine beta-naphthylamide (PAbetaN) inhibits the activities of
      AcrAB and AcrEF and/or acts synergistically with antibiotics by destabilizing the
      outer membrane permeability barrier. Real-time efflux assays allowed a clear
      distinction between the efflux pump-inhibiting activity of PAbetaN and the outer
      membrane-destabilizing action of polymyxin B nonapeptide (PMXBN). When added in
      equal amounts, PAbetaN, but not PMXBN, strongly inhibited the efflux activities
      of both AcrAB and AcrEF pumps. In contrast, when outer membrane destabilization
      was assessed by the nitrocefin hydrolysis assay, PMXBN exerted a much greater
      damaging effect than PAbetaN. Strong action of PAbetaN in inhibiting efflux
      activity compared to its weak action in destabilizing the outer membrane
      permeability barrier suggests that PAbetaN acts mainly by inhibiting efflux
      pumps. We concluded that at low concentrations, PAbetaN acts specifically as an
      inhibitor of both AcrAB and AcrEF efflux pumps; however, at high concentrations,
      PAbetaN in the efflux-proficient background not only inhibits efflux pump
      activity but also destabilizes the membrane. The effects of PAbetaN on membrane
      integrity are compounded in cells unable to extrude PAbetaN. IMPORTANCE: The
      increase in multidrug-resistant bacterial pathogens at an alarming rate has
      accelerated the need for implementation of better antimicrobial stewardship,
      discovery of new antibiotics, and deeper understanding of the mechanism of drug
      resistance. The work carried out in this study highlights the importance of
      employing real-time fluorescence-based assays in differentiating multidrug efflux
      inhibitory and outer membrane-destabilizing activities of antibacterial
      compounds.

PMID- 25962917
TI  - Bacillus anthracis Overcomes an Amino Acid Auxotrophy by Cleaving Host Serum
      Proteins.
AB  - Bacteria sustain an infection by acquiring nutrients from the host to support
      replication. The host sequesters these nutrients as a growth-restricting
      strategy, a concept termed "nutritional immunity." Historically, the study of
      nutritional immunity has centered on iron uptake because many bacteria target
      hemoglobin, an abundant circulating protein, as an iron source. Left unresolved
      are the mechanisms that bacteria use to attain other nutrients from host sources,
      including amino acids. We employed a novel medium designed to mimic the chemical
      composition of human serum, and we show here that Bacillus anthracis, the
      causative agent of anthrax disease, proteolyzes human hemoglobin to liberate
      essential amino acids which enhance its growth. This property can be traced to
      the actions of InhA1, a secreted metalloprotease, and extends to at least three
      other serum proteins, including serum albumin. The results suggest that we must
      also consider proteolysis of key host proteins to be a way for bacterial
      pathogens to attain essential nutrients, and we provide an experimental framework
      to determine the host and bacterial factors involved in this process. IMPORTANCE:
      The mechanisms by which bacterial pathogens acquire nutrients during infection
      are poorly understood. Here we used a novel defined medium that approximates the
      chemical composition of human blood serum, blood serum mimic (BSM), to better
      model the nutritional environment that pathogens encounter during bacteremia.
      Removing essential amino acids from BSM revealed that two of the most abundant
      proteins in blood-hemoglobin and serum albumin-can satiate the amino acid
      requirement for Bacillus anthracis, the causative agent of anthrax. We further
      demonstrate that hemoglobin is proteolyzed by the secreted protease InhA1. These
      studies highlight that common blood proteins can be a nutrient source for
      bacteria. They also challenge the historical view that hemoglobin is solely an
      iron source for bacterial pathogens.

PMID- 25962918
TI  - The PduL Phosphotransacylase Is Used To Recycle Coenzyme A within the Pdu
      Microcompartment.
AB  - In Salmonella enterica, 1,2-propanediol (1,2-PD) utilization (Pdu) is mediated by
      a bacterial microcompartment (MCP). The Pdu MCP consists of a multiprotein shell
      that encapsulates enzymes and cofactors for 1,2-PD catabolism, and its role is to
      sequester a reactive intermediate (propionaldehyde) to minimize cellular toxicity
      and DNA damage. For the Pdu MCP to function, the enzymes encapsulated within must
      be provided with a steady supply of substrates and cofactors. In the present
      study, Western blotting assays were used to demonstrate that the PduL
      phosphotransacylase is a component of the Pdu MCP. We also show that the N
      terminal 20-residue-long peptide of PduL is necessary and sufficient for
      targeting PduL and enhanced green fluorescent protein (eGFP) to the lumen of the
      Pdu MCP. We present the results of genetic tests that indicate that PduL plays a
      role in the recycling of coenzyme A internally within the Pdu MCP. However, the
      results indicate that some coenzyme A recycling occurs externally to the Pdu MCP.
      Hence, our results support a model in which a steady supply of coenzyme A is
      provided to MCP lumen enzymes by internal recycling by PduL as well as by the
      movement of coenzyme A across the shell by an unknown mechanism. These studies
      expand our understanding of the Pdu MCP, which has been linked to enteric
      pathogenesis and which provides a possible basis for the development of
      intracellular bioreactors for use in biotechnology. IMPORTANCE: Bacterial MCPs
      are widespread organelles that play important roles in pathogenesis and global
      carbon fixation. Here we show that the PduL phosphotransacylase is a component of
      the Pdu MCP. We also show that PduL plays a key role in cofactor homeostasis by
      recycling coenzyme A internally within the Pdu MCP. Further, we identify a
      potential N-terminal targeting sequence using a bioinformatic approach and show
      that this short sequence extension is necessary and sufficient for directing PduL
      as well as heterologous proteins to the lumen of the Pdu MCP. These findings
      expand our general understanding of bacterial MCP assembly and cofactor
      homeostasis.

PMID- 25962919
TI  - Pharmacogenomics of EGFR-targeted therapies in non-small cell lung cancer: EGFR
      and beyond.
AB  - Commonly observed aberrations in epidermal growth factor receptor (EGFR)
      signaling have led to the development of EGFR-targeted therapies for various
      cancers, including non-small cell lung cancer (NSCLC). EGFR mutations and
      overexpression have further been shown to modulate sensitivity to these EGFR
      targeted therapies in NSCLC and several other types of cancers. However, it is
      clear that mutations and/or genetic variations in EGFR alone cannot explain all
      of the variability in the responses of patients with NSCLC to EGFR-targeted
      therapies. For instance, in addition to EGFR genotype, genetic variations in
      other members of the signaling pathway downstream of EGFR or variations in
      parallel receptor tyrosine kinase (RTK) pathways are now recognized to have a
      significant impact on the efficacy of certain EGFR-targeted therapies. In this
      review, we highlight the mutations and genetic variations in such genes
      downstream of EGFR and in parallel RTK pathways. Specifically, the directional
      effects of these pharmacogenetic factors are discussed with a focus on two
      commonly prescribed EGFR inhibitors: cetuximab and erlotinib. The results of this
      comprehensive review can be used to optimize the treatment of NSCLC with EGFR
      inhibitors. Furthermore, they may provide the rationale for the design of
      subsequent combination therapies that involve the inhibition of EGFR. 

PMID- 25962920
TI  - Visual Responsiveness of Neurons in the Secondary Somatosensory Area and its
      Surrounding Parietal Operculum Regions in Awake Macaque Monkeys.
AB  - Previous neurophysiological studies performed in macaque monkeys have shown that
      the secondary somatosensory cortex (SII) is essentially engaged in the processing
      of somatosensory information and no other sensory input has been reported. In
      contrast, recent human brain-imaging studies have revealed the effects of visual
      and auditory stimuli on SII activity, which suggest multisensory integration in
      the human SII. To determine whether multisensory responses of the SII also exist
      in nonhuman primates, we recorded single-unit activity in response to visual and
      auditory stimuli from the SII and surrounding regions in 8 hemispheres from 6
      awake monkeys. Among 1157 recorded neurons, 306 neurons responded to visual
      stimuli. These visual neurons usually responded to rather complex stimuli, such
      as stimulation of the peripersonal space (40.5%), observation of human action
      (29.1%), and moving-object stimulation outside the monkey's reach (23.9%). We
      occasionally applied auditory stimuli to visual neurons and found 10 auditory
      responsive neurons that exhibited somatosensory responses. The visual neurons
      were distributed continuously along the lateral sulcus covering the entire SII,
      along with other somatosensory neurons. These results highlight the need to
      investigate novel functional roles-other than somesthetic sensory processing-of
      the SII. 

PMID- 25962922
TI  - Benefits and risks associated with consumption of raw, cooked, and canned tuna
      (Thunnus spp.) based on the bioaccessibility of selenium and methylmercury.
AB  - The Se, Hg, and methylmercury (MeHg) levels in raw, cooked (boiled and grilled),
      and canned tuna (Thunnus spp.) were determined before and after an in vitro
      digestion, thereby enabling the calculation of the respective bioaccessibility
      percentages. A risk-benefit evaluation of raw and canned tuna on the basis of the
      Se and MeHg data was performed. Selenium bioaccessibility was high in tuna,
      though slightly lower in canned than in raw products. Mercury levels were high in
      raw and cooked tuna. Hg bioaccessibility percentages were low (39-48%) in the
      cooked tuna and even lower (<20%) in canned tuna. For the bioaccessible fraction,
      all molar Se:MeHg ratios were higher than one (between 10 and 74). A
      probabilistic assessment of MeHg risk vs Se benefit showed that while a weekly
      meal of canned tuna presents very low risk, raw, boiled, and grilled tuna
      consumption should not exceed a monthly meal, at least, for pregnant and nursing
      women. 

PMID- 25962923
TI  - Neuropsychological scores and WeeFIM cognitive ratings of children with traumatic
      brain injury: A brief report.
AB  - PRIMARY OBJECTIVE AND HYPOTHESIS: To test the hypothesis that there is a
      significant relationship between WeeFIM ratings of cognitive functioning and
      performance on neuropsychological tests of children with traumatic brain injury
      (TBI). DESIGN: Retrospective analysis of archival data. PARTICIPANTS: Data from
      52 children with severe TBI collected during inpatient rehabilitation. MAIN
      OUTCOME MEASURES: Multiple regression analysis with Neuropsychological test
      scores from Wechsler Abbreviated Scale of Intelligence (WASI) and Children's
      Memory Scale (CMS) entered as predictor variables and WeeFIM cognitive ratings as
      criteria variables. RESULTS: Analyses revealed significant relationships between
      WeeFIM cognitive rating and neuropsychological test scores. Delayed verbal memory
      was most highly associated with WeeFIM cognitive ratings. CONCLUSIONS: Results
      support the hypothesis of significant relationships between neuropsychological
      performance and WeeFIM ratings of children with TBI and support generalizability
      of neuropsychological performance to daily cognitive functioning.

PMID- 25962921
TI  - Motor Circuit Anatomy in Children with Autism Spectrum Disorder With or Without
      Attention Deficit Hyperactivity Disorder.
AB  - This study examined the morphology of frontal-parietal regions relevant to motor
      functions in children with autism spectrum disorder (ASD) with or without
      attention deficit hyperactivity disorder (ADHD). We also explored its
      associations with autism severity and motor skills, and the impact of comorbid
      ADHD on these associations. Participants included 126 school-age children: 30 had
      ASD only, 33 had ASD with ADHD, and 63 were typically developing. High resolution
      3T MPRAGE images were acquired to examine the cortical morphology (gray matter
      volume, GMV, surface area, SA, and cortical thickness, CT) in three regions of
      interest (ROI): precentral gyrus (M1), postcentral gyrus (S1), and inferior
      parietal cortex (IPC). Children with ASD showed abnormal increases in GMV and SA
      in all three ROIs: (a) increased GMV in S1 bilaterally and in right M1 was
      specific to children with ASD without ADHD; (b) all children with ASD (with or
      without ADHD) showed increases in the left IPC SA. Furthermore, on measures of
      motor function, impaired praxis was associated with increased GMV in right S1 in
      the ASD group with ADHD. Children with ASD with ADHD showed a positive
      relationship between bilateral S1 GMV and manual dexterity, whereas children with
      ASD without ADHD showed a negative relationship. Our findings suggest that (a)
      ASD is associated with abnormal morphology of cortical circuits crucial to motor
      control and learning; (b) anomalous overgrowth of these regions, particularly S1,
      may contribute to impaired motor skill development, and (c) functional and
      morphological differences are apparent between children with ASD with or without
      ADHD.

PMID- 25962924
TI  - Predictors of productivity outcomes for secondary and tertiary students following
      traumatic brain injury.
AB  - PRIMARY OBJECTIVE: This prospective longitudinal study aimed to identify rates
      and predictors of productivity outcomes (educational or vocational) at 1 year
      post-injury in young people studying prior to sustaining a traumatic brain injury
      (TBI). METHODS AND PROCEDURES: A total of n = 145 with complicated mild-severe
      injuries, studying at secondary (45.2%) or tertiary (54.8%) levels pre-injury,
      participated. Mean age at injury = 18.6 years (SD = 3.29) and mean duration of
      PTA = 21.9 days (SD = 27.18). Pre-injury demographic (gender, age, level of
      study, living situation), injury related (severity, physical injuries) and
      concurrent post-injury (independence in ADLs and self-reported cognitive,
      behavioural, emotional sequelae) predictors were entered into logistic
      regressions. MAIN OUTCOMES: Of those participants categorized as 'productive'
      (79.3%), 60% were studying, with 40% employed. Participants with longer PTA and
      those with reduced initiative and self-centredness were less likely to be
      'productive'. The overall relationship between PTA and productivity appeared to
      be linear in nature, with PTA duration of more than 80 days, reducing the
      probability of being productive at 1 year to 50%. CONCLUSIONS: PTA duration and
      behavioural sequelae were the strongest predictors of productivity in those
      studying prior to injury. Allied health supports should be targeted towards
      reducing the impact of and compensating for barriers such as reduced initiative
      in order to maximize productive outcomes in this group.

PMID- 25962925
TI  - Relatives of patients with severe brain injury: Growth curve analysis of anxiety
      and depression the first year after injury.
AB  - PRIMARY OBJECTIVE: To investigate trajectories and predictors of trajectories of
      anxiety and depression in relatives of patients with a severe brain injury during
      the first year after injury. RESEARCH DESIGN: A prospective longitudinal study
      with four repeated measurements. SUBJECTS: Ninety relatives of patients with
      severe brain injury. METHODS: The relatives were assessed on the anxiety and
      depression scales from the Symptom Checklist-90-Revised and latent variable
      growth curve models were used to model the trajectories. The effects of patient's
      age, patient's Glasgow Coma Score, level of function and consciousness, gender
      and relationship of the relatives were modelled. RESULTS: Improvement was found
      in both symptoms of anxiety and depression during the 12-month study period. The
      analysis revealed different trajectories for symptoms of anxiety and depression,
      as anxiety had a more rapid improvement. Higher initial level of symptoms of
      depression was seen in female relatives. Higher initial level of anxiety was
      associated with younger patient age, lower level of function and consciousness in
      the patient and the relative being female or the spouse. CONCLUSION: Future
      research and interventions should focus not only on specific deficits in the
      patient, but also on how the emotional state and well-being of the relatives
      evolve, while trying to adjust and cope with a new life-situation.

PMID- 25962926
TI  - Trends in incidence and severity of sports-related traumatic brain injury (TBI)
      in the emergency department, 2006-2011.
AB  - OBJECTIVE: To characterize and identify trends in sports-related traumatic brain
      injury (TBI) emergency department (ED) visits from 2006-2011. METHODS: This study
      reviewed data on sports-related TBI among individuals under age 65 from the
      Nationwide Emergency Department Sample from 2006-2011. Visits were stratified by
      age, sex, injury severity, payer status and other criteria. Variations in
      incidence and severity were examined both between groups and over time. Odds of
      inpatient admission were calculated using regression modelling. RESULTS: Over the
      period examined, 489 572 sports-related TBI ED visits were reported. The majority
      (62.2%) of these visits occurred among males under the age of 18. The average
      head Abbreviated Injury Severity score among these individuals was 1.93 (95% CI =
      1.93-1.94) and tended to be lowest among those in middle school and high school
      age groups; these were also less likely to be admitted. The absolute annual
      number of visits grew 65.9% from 2006 until 2011, with the majority of this
      growth occurring among children under age 15. Hospitalization rates dropped 35.6%
      over the same period. CONCLUSION: Changes in year-over-year presentation rates
      vs. hospitalization rates among young athletes suggest that players, coaches and
      parents may be more aware of sports-related TBI and have developed lower
      thresholds for seeking medical attention.

PMID- 25962927
TI  - Community integration 2 years after moderate and severe traumatic brain injury.
AB  - OBJECTIVE: The aim of this study was to examine community integration by the
      Community Integration Questionnaire (CIQ) 2 years after injury in a divided TBI
      sample of moderately and severely injured patients. The second aim was to
      identify social-demographic, injury-related and rehabilitation associated
      predictors of CIQ. DESIGN: A cohort study. SETTING: Outpatient follow-up.
      PARTICIPANTS: Fifty-seven patients with moderate (n = 21) or severe (n = 36) TBI
      were examined with the Community Integration Questionnaire (CIQ) at 2 years after
      injury. Possible predictors were analysed in a regression model using CIQ total
      score at 2 years as the outcome measure. MAIN OUTCOME MEASURES: The Community
      Integration Questionnaire. RESULTS: At 2 years follow-up, there was significant
      difference between the moderately and severely injured patients in the
      productivity scores (p < 0.003), while difference in the total CIQ scores
      approached the significance level (p = 0.074). Significant predictors of a higher
      CIQ score were living with a spouse, higher Glasgow Coma Scale (GCS) in the acute
      phase, shorter Post-Traumatic Amnesia (PTA), longer rehabilitation stay (LOS) and
      use of rehabilitation service. Use of rehabilitation service (B = 7.766) and
      living with a spouse (B = 4.251) had the largest influence. This means that
      living with a spouse, better score on the GCS scale, shorter PTA, longer LOS and
      use of rehabilitation service after discharge equated to better community
      integration 2 years after TBI Conclusions: Two years after TBI the moderately
      injured patients have a higher productivity level than the severely injured
      patients. Marital status, injury severity and rehabilitation after injury were
      associated with community integration 2 years after TBI.

PMID- 25962928
TI  - Physical Activity, Obesity Status, and Blood Pressure in Preschool Children.
AB  - OBJECTIVE: To examine the combined effects of physical activity and weight status
      on blood pressure (BP) in preschool-aged children. STUDY DESIGN: The sample
      included 733 preschool-aged children (49% female). Physical activity was
      objectively assessed on 7 consecutive days by accelerometry. Children were
      categorized as sufficiently active if they met the recommendation of at least 60
      minutes daily of moderate-to-vigorous physical activity (MVPA). Body mass index
      was used to categorize children as nonoverweight or overweight/obese, according
      to the International Obesity Task Force benchmarks. BP was measured using an
      automated BP monitor and categorized as elevated or normal using BP percentile
      based cut-points for age, sex, and height. RESULTS: The prevalence of elevated
      systolic BP (SBP) and diastolic BP was 7.7% and 3.0%, respectively. The
      prevalence of overweight/obese was 32%, and about 15% of children did not
      accomplish the recommended 60 minutes of daily MVPA. After controlling for age
      and sex, overweight/obese children who did not meet the daily MVPA recommendation
      were 3 times more likely (OR 3.8; CI 1.6-8.6) to have elevated SBP than
      nonoverweight children who met the daily MVPA recommendation. CONCLUSIONS:
      Overweight or obese preschool-aged children with insufficient levels of MVPA are
      at significantly greater risk for elevated SBP than their nonoverweight and
      sufficiently active counterparts.

PMID- 25962929
TI  - Vaccine-Associated Herpes Zoster.

PMID- 25962930
TI  - Randomized Clinical Trial of Preoperative Feeding to Evaluate Intestinal Barrier
      Function in Neonates Requiring Cardiac Surgery.
AB  - OBJECTIVES: To evaluate intestinal barrier function in neonates undergoing
      cardiac surgery using lactulose/mannitol (L/M) ratio measurements, and to
      determine correlations with early breast milk feeding. STUDY DESIGN: This was a
      single-center, prospective, randomized pilot study of 27 term-born neonates (>=
      37 weeks gestation) requiring cardiac surgery who were randomized to 1 of 2
      preoperative feeding groups: nil per os (NPO) or trophic (10 mL/kg/day) breast
      milk feeds. At 3 time points (preoperative [preop], postoperative [postop] day 7,
      and postop day 14), subjects were administered an oral L/M solution, after which
      urine L/M ratios were measured using gas chromatography, with higher ratios
      indicative of increased intestinal permeability. Trends over time in the mean
      urine L/M ratios for each group were estimated using a general linear mixed
      model. RESULTS: There were no adverse events related to preoperative trophic
      feeding. In the NPO group (n = 13), the mean urine L/M ratio was 0.06 at preop,
      0.12 at postop day 7, and 0.17 at postop day 14. In the trophic breast milk feeds
      group (n = 14), the mean urine L/M ratio was 0.09 at preop, 0.19 at postop day 7,
      and 0.15 at postop day 14. In both groups, L/M ratios were significantly higher
      at postop day 7 and postop day 14 compared with preop (P < .05). CONCLUSION:
      Neonates have increased intestinal permeability after cardiac surgery extending
      to at least postop day 14. This pilot study was not powered to detect differences
      in benefit or adverse events comparing the NPO and trophic breast milk feeds
      groups. Further studies to identify mechanisms of intestinal injury and
      therapeutic interventions are warranted. TRIAL REGISTRATION: Registered with
      ClinicalTrials.gov: NCT01475357.

PMID- 25962932
TI  - Aneurysmal Bone Cyst of the Occipital Bone.

PMID- 25962931
TI  - Age at Menarche and Cardiometabolic Risk in Adulthood: The Coronary Artery Risk
      Development in Young Adults Study.
AB  - OBJECTIVE: To examine the association of menarche timing with cardiometabolic
      risk factors into early to mid-adulthood, comparing African American and White
      women. STUDY DESIGN: Analyses included 2583 women (African American = 1333; White
      = 1250) from the Coronary Artery Risk Development in Young Adults cohort study
      over 25 years of follow-up (1985-2011). Outcomes included type 2 diabetes,
      metabolic syndrome, adiposity, glucose, insulin, blood pressure, and blood
      lipids. Cox models or repeated measures linear regression models estimated the
      association between age at menarche and the outcomes. RESULTS: Each 1-year
      earlier age at menarche was associated with higher mean body mass index among
      African American (0.88 +/- 0.12 kg/m(2), P < .0001) and White (0.89 +/- 0.10
      kg/m(2), P < .0001) women. After body mass index adjustment, each 1-year earlier
      age at menarche was associated with higher triglycerides (2.26 +/- 0.68 mg/dL, P
      = .001) and glucose (0.34 +/- 0.11 mg/dL, P = .002), and greater risk for
      incident impaired fasting glucose (hazard ratio = 1.13, 95% CI 1.04-1.20) and
      metabolic syndrome (hazard ratio 1.19, 95% CI 1.11-1.26) among White women only.
      CONCLUSIONS: Excess adiposity associated with earlier menarche is sustained
      through mid-adulthood, and primarily drives higher cardiometabolic risk factor
      levels. However, White women with earlier menarche had increased risk of a number
      of insulin-resistance related conditions independent of adiposity. The
      cardiometabolic impact of earlier menarche was weaker in African American women
      despite higher average adiposity. Weight maintenance would likely reduce but may
      not completely eliminate the elevated cardiometabolic risk of earlier menarche.

PMID- 25962933
TI  - Markers of Insulin Sensitivity in 12-Year-Old Children Born from Preeclamptic
      Pregnancies.
AB  - OBJECTIVE: To determine whether maternal preeclampsia influences insulin
      sensitivity (IS) or its biochemical markers in offspring. STUDY DESIGN: Sixty
      children born from a preeclamptic pregnancy (PRE) and 60 matched control subjects
      born from a normotensive pregnancy (non-PRE) were studied at age 12 years. IS was
      estimated using the Quantitative Insulin Sensitivity Check Index (QUICKI), and
      serum concentrations of adiponectin, leptin, insulin-like growth factor (IGF)-1,
      IGF-2, IGF-binding protein-1 (IGFBP-1), sex hormone-binding globulin, lipids, and
      casual blood pressure (BP) were measured. RESULTS: The mean values of QUICKI,
      serum adiponectin, leptin, IGF-1, IGF-2, IGFBP-1, and sex hormone-binding
      globulin did not differ between the PRE group and non-PRE group (P > .05 for
      all). The PRE subjects with the lowest IS (the lowest QUICKI tertile; n = 20) had
      significantly higher mean serum leptin (P = .007), triglyceride (P = .008), and
      IGF-1 (P = .005) levels and systolic BP (P = .019), and lower serum IGFBP-1 level
      (P = .007) compared with PRE subjects with higher QUICKI values (n = 40).
      Similarly, in logistic regression analysis, higher serum leptin (OR, 1.2; P =
      .009), triglyceride (OR, 1.2; P = .040), and IGF-1 (OR, 1.1; P = .031) levels and
      systolic BP (OR, 5.8; P = .024) were associated with low QUICKI in the PRE group.
      CONCLUSION: Maternal preeclampsia did not produce decreased IS in offspring by
      age of 12 years. However, the offspring with the lowest IS had higher mean serum
      triglyceride level and systolic BP, suggesting that components of the metabolic
      syndrome may cluster in this subgroup.

PMID- 25962934
TI  - Electrocardiographic Versus Echocardiographic Left Ventricular Hypertrophy in
      Prediction of Congestive Heart Failure in the Elderly.
AB  - BACKGROUND: Left ventricular hypertrophy (LVH) is an established risk factor for
      heart failure (HF) and is a component of the Framingham Heart Failure Risk Score
      (FHFRS). Whether LVH detected by electrocardiogram (ECG-LVH) is equally
      predictive of HF as LVH detected by echocardiography (echo-LVH) is unclear.
      HYPOTHESIS: ECG-LVH and echo-LVH are equally predictive of HF. METHODS: This
      analysis included 4543 participants (85% white; 41% male) age >= 65 years from
      the Cardiovascular Health Study who were free of HF at baseline. Incident HF was
      identified during a median follow-up of 12 years. ECG-LVH was defined by the
      Cornell criteria. Echo-LVH was defined as left ventricular mass > 95th percentile
      (male, > 212 g; female, > 175 g). Cox proportional hazard regression was used to
      examine the association between ECG-LVH and echo-LVH, separately with incident
      HF. Harrell's concordance C-index was calculated for the FHFRS with inclusion of
      ECG-LVH and echo-LVH, separately. RESULTS: At baseline, 168 participants had ECG
      LVH and 226 had echo-LVH. A total of 1380 incident HF events occurred during
      follow-up. Both ECG-LVH and echo-LVH were predictive of incident HF (for ECG-LVH,
      hazard ratio: 1.39, 95% confidence interval [CI]: 1.08-1.77; for echo-LVH, hazard
      ratio: 1.52, 95% CI: 1.22-1.89). The ability of the FHFRS to predict HF was
      similar when ECG-LVH (C-index: 0.772, 95% CI: 0.726-0.815) and echo-LVH (C-index:
      0.772, 95% CI: 0.727-0.814) were included into the model separately. CONCLUSIONS:
      Both LVH-ECG and echo-LVH are equally predictive of incident HF and can be used
      interchangeably in HF risk-prediction models.

PMID- 25962935
TI  - Single-Walled TiO2 Nanotubes: Enhanced Carrier-Transport Properties by TiCl4
      Treatment.
AB  - In the present work we report significant enhancement of the photoelectrochemical
      properties of self- organized TiO2 nanotubes by a combined "de-coring" of classic
      nanotubes followed by an appropiate TiCl4 treatment. We show that, except for the
      expected particle decoration, a key effect of the TiCl4 treatment is that the
      electron transport characteristics in TiO2 nanotubes can be drastically improved,
      for example, we observe an enhancement of up to 70 % in electron-transport times.

PMID- 25962937
TI  - Endoscopic Suturing for Ulcer Exclusion in Patients With Massively Bleeding Large
      Gastric Ulcer.

PMID- 25962936
TI  - Maintenance of Clonogenic KIT(+) Human Colon Tumor Cells Requires Secretion of
      Stem Cell Factor by Differentiated Tumor Cells.
AB  - BACKGROUND & AIMS: Colon tumors contain a fraction of undifferentiated stem cell
      like cancer cells with high tumorigenic potential. Little is known about the
      signals that maintain these stem-like cells. We investigated whether
      differentiated tumor cells provide support. METHODS: We established
      undifferentiated colonosphere cultures from human colon tumors and used them to
      generate stably differentiated cell lines. Antibody arrays were used to identify
      secreted factors. Expression of genes involved in stemness, differentiation, and
      the epithelial to mesenchymal transition was measured using reverse transcription
      quantitative polymerase chain reaction. Expression of KIT in human tumors was
      analyzed with gene expression arrays and by immunohistochemistry. Colonospheres
      were injected into the livers of CBy.Cg-Foxn1nu/J mice. After liver tumors had
      formed, hypoxia was induced by vascular clamping. RESULTS: Differentiated cells
      from various tumors, or medium conditioned by them, increased the clonogenic
      capacity of colonospheres. Stem cell factor (SCF) was secreted by differentiated
      tumor cells and supported the clonogenic capacity of KIT(+) colonosphere cells.
      Differentiated tumor cells induced the epithelial to mesenchymal transition in
      colonosperes; this was prevented by inhibition of KIT or SCF. SCF prevented loss
      of clonogenic potential under differentiation-inducing conditions. Suppression of
      SCF or KIT signaling greatly reduced the expression of genes that regulate
      stemness and the epithelial to mesenchymal transition and inhibited clonogenicity
      and tumor initiation. Bioinformatic and immunohistochemical analyses revealed a
      correlation between expression of KIT- and hypoxia-related genes in colon tumors,
      which was highest in relapse-prone mesenchymal-type tumors. Hypoxia induced
      expression of KIT in cultured cells and in human colon tumor xenografts and this
      contributed to the clonogenic capacity of the tumor cells. CONCLUSIONS: Paracrine
      signaling from SCF to KIT, between differentiated tumor cells and
      undifferentiated stem-like tumor cells, helps maintain the stem-like features of
      tumor cells, predominantly under conditions of hypoxia.

PMID- 25962938
TI  - Adjusting for population shifts and covariates in space-time interaction tests.
AB  - Statistical tests for epidemic patterns use measures of space-time event
      clustering, and look for high levels of clustering that are unlikely to appear
      randomly if events are independent. Standard approaches, such as Knox's (1964,
      Applied Statistics 13, 25-29) test, are biased when the spatial distribution of
      population changes over time, or when there is space-time interaction in
      important background variables. In particular, the Knox test is too sensitive to
      coincidental event clusters in such circumstances, and too likely to raise false
      alarms. Kulldorff and Hjalmars (1999, Biometrics 55, 544-552) proposed a variant
      of Knox's test to control for bias caused by population shifts. In this article,
      I demonstrate that their test is also generally biased, in an unknown direction.
      I suggest an alternative approach that accounts for exposure shifts while also
      conditioning on the observed spatial and temporal margins of event counts, as in
      the original Knox test. The new approach uses Metropolis sampling of
      permutations, and is unbiased under more general conditions. I demonstrate how
      the new method can also include controls for the clustering effects of
      covariates. 

PMID- 25962939
TI  - miR-433 inhibits oral squamous cell carcinoma (OSCC) cell growth and metastasis
      by targeting HDAC6.
AB  - OBJECTIVES: The aim of this study was to determine expression levels of miR-433
      in oral squamous cell carcinomas (OSCCs) and adjacent normal tissues, and explore
      its biological functions in OSCCs. METHODS: miR-433 level in oral squamous cell
      carcinomas (OSCCs) and adjacent normal tissues was tested by real-time qPCR. The
      effect of miR-433 on cell growth was detected by MTT and colony formation assays.
      The tumorigenicity of miR-433 transfected OSCCs was evaluated in nude mice model.
      Transwell and wound healing assays were performed to detect the effect of miR-433
      on OSCCs cell invasion and migration. Luciferase reporter gene assays were
      performed to identify the interaction between miR-433 and 3'UTR of HDAC6 mRNA.
      The protein level of HDAC6, BCL2, CCNE1, MMP1 and MMP9 was determined by Western
      blotting. Immunohistochemistry analysis was performed to detect the expression of
      HDAC6 in oral squamous cell carcinomas (OSCCs) and adjacent normal tissues.
      RESULTS: We found that miR-433 was frequently down-regulated in OSCCs compared
      with adjacent normal tissues. Restoring miR-433 expression in OSCC cells
      dramatically suppressed cells growth, invasion and migration. Importantly, our
      data showed that miR-433 downregulated the expression of HDAC6 through directly
      targeting its 3'UTR. CONCLUSION: Our data suggest that miR-433 exerts its tumor
      suppressor function by targeting HDAC6, leading to the inhibition of OSCC cell
      growth, invasion and migration, which suggest that miR-433 may be potential
      target for diagnostic and therapeutic applications in OSCC.

PMID- 25962940
TI  - The submental island flap for the treatment of intraoral tumor-related defects:
      No effect on recurrence rates.
AB  - OBJECTIVES: The submental island flap has become increasingly popular in the
      treatment of intraoral defects following tumor ablation. However, there was
      concern that the elevation of the pedicled flap might interfere with the
      efficiency of level I-lymph node dissection and decrease the oncologic prognosis
      of the patients. MATERIALS AND METHODS: In a prospective clinical study over five
      years the outcome of 45 consecutive patients with intraoral cancer of various T
      stages treated with submental island flaps was evaluated and compared to 45
      patients with a T-status analogous oral cancer treated with free radial forearm
      flaps. RESULTS: All submental island flaps beside three were successful (93.3%).
      The obtained functional results were pleasing and the donor morbidity low.
      Patients treated with submental island flaps exhibited no enhanced risk of local
      tumor recurrence or lymph node metastasis (p<0.86). In contrast, the operation
      time, time of intensive care and hospitalization were reduced (p<0.001).
      DISCUSSION: We conclude that the submental island flap is an effective and
      predictable option of small and medium-sized oral defect treatment. It is a
      valuable alternative to free flap soft tissue reconstructions such as radial
      forearm or perforator flaps. It seems particularly beneficial to patients with
      relevant comorbidities as often present in the oral cancer population. The
      application of the submental island flap does not reduce the oncological
      prognosis of oral cancer patients.

PMID- 25962941
TI  - Familial clustering of risk factors for cardiovascular disease among first-degree
      relatives of patients with chronic kidney disease in a sub-Saharan African
      population.
AB  - OBJECTIVE: To determine the prevalence of risk factors for cardiovascular disease
      (CVD) in first-degree relatives (FDRs) of patients with chronic kidney disease
      (CKD) in a sub-Saharan African population. METHODS: This was a cross-sectional
      survey of 460 subjects (230 FDRs of patients with CKD and 230 healthy controls).
      Anthropometrics and blood pressures were measured. Spot urine and fasting venous
      blood samples were obtained for biochemical analysis. RESULTS: The prevalence of
      hypertension, diabetes mellitus, obesity and dyslipidaemia were significantly
      higher in FDRs of patients with CKD compared with the controls: 56 (24.3%) vs 29
      (12.6%), p = 0.01; 20 (8.7%) vs 6 (2.6%), p = 0.01; 40 (17.4%) vs 24 (10.4%), p =
      0.03 and 171 (74.3%) vs 138 (60.0%), p = 0.01, respectively. Hypertension (OR,
      1.65), dyslipidaemia (OR, 1.72) and albuminuria (OR, 1.61) were independently
      associated with being a FDR of patients with CKD. CONCLUSION: In this sub-Saharan
      African population, risk factors for CVD were more prevalent in the FDRs of
      patients with CKD than in healthy controls.

PMID- 25962942
TI  - Strategic investments in non-communicable diseases (NCD) research in Africa: the
      GSK Africa NCD Open Lab.
AB  - In March 2014, GSK announced a number of new strategic investments in Africa. One
      of these included investment of up to 25 million Pounds Sterling (L25 million) to
      create the world's first R&D Open Lab to increase understanding of non
      communicable diseases (NCDs) in Africa. The vision is to create a new global R&D
      effort with GSK working in partnership with major funders, academic centres and
      governments to share expertise and resources to conduct high-quality research.
      The Africa NCD Open Lab will see GSK scientists collaborate with scientific
      research centres across Africa. An independent advisory board of leading
      scientists and clinicians will provide input to develop the strategy and
      selection of NCD research projects within a dynamic and networked open-innovation
      environment. It is hoped that these research projects will inform prevention and
      treatment strategies in the future and will enable researchers across academia
      and industry to discover and develop new medicines to address the specific needs
      of African patients. 

PMID- 25962943
TI  - NHLBI perspectives on the growth of heart, lung, blood and sleep conditions in
      Africa: global and domestic insights, challenges and opportunities.

PMID- 25962944
TI  - Rheumatic heart disease in Africa: is there a role for genetic studies?
AB  - Rheumatic heart disease (RHD) constitutes a leading cause of premature death and
      incapacity in Africa, where it is encountered in younger people, and shows a much
      faster and more malignant course than that seen in Europe or North America. While
      it is well established that RHD is a consequence of recurrent, untreated group A
      beta-haemolytic streptococcal infections (GAS), the pathogenesis is incompletely
      understood, and the variation in natural history and phenotypes are not fully
      explained. In Africa patients are rarely diagnosed with acute rheumatic fever
      (ARF). They usually present in the late stages of RHD, with the severe and
      virulent forms occurring at early ages, therefore leading to high morbidity and
      mortality in young patients. Evidence suggests that genetic factors may be
      involved in determining susceptibility to ARF as well as the severity and
      outcomes of RHD. However, the results of genetic studies have been inconsistent,
      and conflicting results have been found in series from Africa when compared to
      other parts of the globe. Genetic studies in the African context are therefore
      justified to understand the genomic and epigenetic drivers of heterogeneity in
      individual responses to GAS infections and progression to RHD. Platforms such as
      the global registry of RHD represent an opportunity for adequately powered genome
      wide association studies. The discovery of all genetic susceptibility loci
      through whole-genome scanning may provide a clinically useful genetic risk
      prediction tool that will potentially allow echocardiographic screening and
      secondary prophylaxis for moderate lesions to be directed to those at higher
      risk, therefore reducing the burden of the disease to the health system, the work
      health force and the communities of this resource-strained continent. 

PMID- 25962946
TI  - H3Africa comes of age.

PMID- 25962945
TI  - The burden of stroke in Africa: a glance at the present and a glimpse into the
      future.
AB  - OBJECTIVE: Information on the current burden of stroke in Africa is limited. The
      aim of this review was to comprehensively examine the current and projected
      burden of stroke in Africa. METHODS: We systematically reviewed the available
      literature (PubMed and AJOL) from January 1960 and June 2014 on stroke in Africa.
      Percentage change in age-adjusted stroke incidence, mortality and disability
      adjusted life years (DALYs) for African countries between 1990 and 2010 were
      calculated from the Global Burden of Diseases (GBD) model-derived figures.
      RESULTS: Community-based studies revealed an age-standardised annual stroke
      incidence rate of up to 316 per 100,000 population, and age-standardised
      prevalence rates of up to 981 per 100,000. Model-based estimates showed
      significant mean increases in age-standardised stroke incidence. The peculiar
      factors responsible for the substantial disparities in incidence velocity,
      ischaemic stroke proportion, mean age and case fatality compared to high-income
      countries remain unknown. CONCLUSIONS: While the available study data and
      evidence are limited, the burden of stroke in Africa appears to be increasing.

PMID- 25962947
TI  - Stroke genomics in people of African ancestry: charting new paths.
AB  - One in six people worldwide will experience a stroke in his/her lifetime. While
      people in Africa carry a disproportionately higher burden of poor stroke
      outcomes, compared to the rest of the world, the exact contribution of genomic
      factors to this disparity is unknown. Despite noteworthy research into stroke
      genomics, studies exploring the genetic contribution to stroke among populations
      of African ancestry in the United States are few. Furthermore, genomics data in
      populations living in Africa are lacking. The wide genomic variation of African
      populations offers a unique opportunity to identify genomic variants with causal
      relationships to stroke across different ethnic groups. The Stroke Investigative
      Research and Educational Network (SIREN), a component of the Human Health and
      Heredity in Africa (H3Africa) Consortium, aims to explore genomic and
      environmental risk factors for stroke in populations of African ancestry in West
      Africa and the United States. In this article, we review the literature on the
      genomics of stroke with particular emphasis on populations of African origin. 

PMID- 25962949
TI  - Endothelial dysfunction: a unifying hypothesis for the burden of cardiovascular
      diseases in sub-Saharan Africa.
AB  - It is well established that the leading causes of death and disability worldwide
      are cardiovascular diseases (CVD), chief among which is ischaemic heart disease.
      However, it is also recognised that ischaemic heart disease frequently coexists
      with other vascular conditions, such as cerebrovascular, renovascular and
      peripheral vascular disease, thus raising the notion of a common underlying
      pathobiology, albeit with differing manifestations, dictated by the implicated
      vascular bed. The understanding that common metabolic and behavioural risk
      factors as well as social determinants and drivers are convergent in the
      development of CVD evokes the idea that the dysfunction of a common bio-molecular
      platform is central to the occurrence of these diseases. The state of endothelial
      activation, otherwise known as endothelial dysfunction, occurs when reactive
      oxygen signalling predominates due to an uncoupled state of endothelial nitric
      oxide synthase (eNOS). This can be a physiological response to stimulation of the
      innate immune system or a pathophysiological response triggered by cardiovascular
      disease risk factors. The conventional wisdom is that the endothelium plays an
      important role in the initiation, progression and development of CVD and other
      non-communicable diseases. Consequently, the endothelium has remarkable relevance
      in clinical and public health practice as well as in health education, health
      promotion, and disease- and risk-factor prevention strategies. It also presents a
      plausible unifying hypothesis for the burden of CVD seen globally and in sub
      Saharan Africa. Importantly, the heterogeneity in individual responses to
      metabolic, behavioural, and social drivers of CVD may stem from a complex
      interplay of these drivers with genomic, epigenetic and environmental factors
      that underpin eNOS uncoupling. Therefore, further biomedical research into the
      underlying genetic and other mechanisms of eNOS uncoupling may enlighten and
      shape strategies for addressing the burden of CVD in sub-Saharan Africa and other
      regions of the world. 

PMID- 25962950
TI  - Mortality from cardiovascular diseases in sub-Saharan Africa, 1990-2013: a
      systematic analysis of data from the Global Burden of Disease Study 2013.
AB  - BACKGROUND: Cardiovascular disease (CVD) has been the leading cause of death in
      developed countries for most of the last century. Most CVD deaths, however, occur
      in low- and middle-income, developing countries (LMICs) and there is great
      concern that CVD mortality and burden are rapidly increasing in LMICs as a result
      of population growth, ageing and health transitions. In sub-Saharan Africa (SSA),
      where all countries are part of the LMICs, the pattern, magnitude and trends in
      CVD deaths remain incompletely understood, which limits formulation of data
      driven regional and national health policies. OBJECTIVE: The aim was to estimate
      the number of deaths, death rates, and their trends for CVD causes of death in
      SSA, by age and gender for 1990 and 2013. METHODS: Age- and gender-specific
      mortality rates for CVD were estimated using the Global Burden of Disease (GBD)
      2010 methods with some refinements made by the GBD 2013 study to improve
      accuracy. Cause of death was estimated as in the GBD 2010 study and updated with
      a verbal autopsy literature review and cause of death ensemble modelling (CODEm)
      estimation for causes with sufficient information. For all quantities reported,
      95% uncertainty intervals (UIs) were also computed. RESULTS: In 2013, CVD caused
      nearly one million deaths in SSA, constituting 38.3% of non-communicable disease
      deaths and 11.3% of deaths from all causes in that region. SSA contributed 5.5%
      of global CVD deaths. There were more deaths in women (512,269) than in men
      (445,445) and more deaths from stroke (409,840) than ischaemic heart disease
      (258,939). Compared to 1990, the number of CVD deaths in SSA increased 81% in
      2013. Deaths for all component CVDs also increased, ranging from a 7% increase in
      incidence of rheumatic heart disease to a 196% increase in atrial fibrillation.
      The age-standardised mortality rate (per 100,000) in 1990 was 327.6 (CI: 306.2
      351.7) and 330.2 (CI: 312.9-360.0) in 2013, representing only a 1% increase in
      more than two decades. CONCLUSIONS: In SSA, CVDs are neither epidemic nor among
      the leading causes of death. However, a significant increase in the number of
      deaths from CVDs has occurred since 1990, largely as a result of population
      growth, ageing and epidemiological transition. Contrary to what has been observed
      in other world regions, the age-adjusted mortality rate for CVD has not declined.
      Another important difference in CVD deaths in SSA is the predominance of stroke
      as the leading cause of death. Attention to aggressive efforts in cardiovascular
      health promotion and CVD prevention, treatment and control in both men and women
      are warranted. Additionally, investments to improve directly enumerated
      epidemiological data for refining the quantitation of risk exposures, death
      certification and burden of disease assessment will be crucial.

PMID- 25962948
TI  - Sickle cell disease and H3Africa: enhancing genomic research on cardiovascular
      diseases in African patients.
AB  - BACKGROUND: Sickle cell disease (SCD) has a high prevalence in sub-Saharan
      Africa. There are several cardiovascular phenotypes in SCD that contribute to its
      morbidity and mortality. DISCUSSION: SCD is characterised by marked clinical
      variability, with genetic factors playing key modulating roles. Studies in
      Tanzania and Cameroon have reported that singlenucleotide polymorphisms in BCL11A
      and HBS1L-MYB loci and co-inheritance of alpha-thalassaemia impact on foetal
      haemoglobin levels and clinical severity. The prevalence of overt stroke among
      SCD patients in Cameroon (6.7%) and Nigeria (8.7%) suggests a higher burden than
      in high-income countries. There is also some evidence of high burden of kidney
      disease and pulmonary hypertension in SCD; however, the burden and genetics of
      these cardiovascular conditions have seldom been investigated in Africa.
      CONCLUSIONS: Several H3Africa projects are focused on cardiovascular diseases and
      present major opportunities to build genome-based research on existing SCD
      platforms in Africa to transform the health outcomes of patients.

PMID- 25962951
TI  - Characters in cartoons with weight problems.

PMID- 25962952
TI  - Medication Adherence Clubs: a potential solution to managing large numbers of
      stable patients with multiple chronic diseases in informal settlements.
AB  - OBJECTIVES: To assess the care of hypertension, diabetes mellitus and/or HIV
      patients enrolled into Medication Adherence Clubs (MACs). METHODS: Retrospective
      descriptive study was carried out using routinely collected programme data from a
      primary healthcare clinic at informal settlement in Nairobi, Kenya. All patients
      enrolled into MACs were selected for the study. MACs are nurse-facilitated mixed
      groups of 25-35 stable hypertension, diabetes mellitus and/or HIV patients who
      met quarterly to confirm their clinical stability, have brief health discussions
      and receive medication. Clinical officer reviewed MACs yearly, when a patient
      developed complications or no longer met stable criteria. RESULTS: A total of
      1432 patients were enrolled into 47 clubs with 109 sessions conducted between
      August 2013 and August 2014. There were 1020 (71%) HIV and 412 (29%) non
      communicable disease patients. Among those with NCD, 352 (85%) had hypertension
      and 60 (15%) had DM, while 12 had HIV concurrent with hypertension. A total of
      2208 consultations were offloaded from regular clinic. During MAC attendance,
      blood pressure, weight and laboratory testing were completed correctly in 98-99%
      of consultations. Only 43 (2%) consultations required referral for clinical
      officer review before their routine yearly appointment. Loss to follow-up from
      the MACs was 3.5%. CONCLUSIONS: This study demonstrates the feasibility and early
      efficacy of MACs for mixed chronic disease in a resource-limited setting. It
      supports burden reduction and flexibility of regular clinical review for stable
      patients. Further assessment regarding long-term outcomes of this model should be
      completed to increase confidence for deployment in similar contexts.

PMID- 25962954
TI  - Implementing a Community Empowerment Center to Build Capacity for Developing,
      Implementing, and Sustaining Interventions to Promote Community Health.
AB  - The Community Empowerment Center used a community-engaged approach to build
      capacity among residents to develop and implement interventions focused on
      creating a healthier environment. The Center partnered with residents living in a
      public housing community and adjacent low-income neighborhood and provided
      support through a mini-grant program. A six-session training program guided
      community members in mini grant development; 25 individuals attended at least one
      session. Six grant proposals were submitted; three were awarded $12,000 each for
      intervention implementation. Findings offer a model for engaging residents from
      low-resource settings in intervention development, implementation, and
      sustainability for community health promotion. 

PMID- 25962953
TI  - A New Paradigm for Individual Subject Language Mapping: Movie-Watching fMRI.
AB  - BACKGROUND: Functional MRI (fMRI) based on language tasks has been used in
      presurgical language mapping in patients with lesions in or near putative
      language areas. However, if patients have difficulty performing the tasks due to
      neurological deficits, it leads to unreliable or noninterpretable results. In
      this study, we investigate the feasibility of using a movie-watching fMRI for
      language mapping. METHODS: A 7-minute movie clip with contrasting speech and
      nonspeech segments was shown to 22 right-handed healthy subjects. Based on all
      subjects' language functional regions-of-interest, 6 language response areas were
      defined, within which a language response model (LRM) was derived by extracting
      the main temporal activation profile. Using a leave-one-out procedure,
      individuals' language areas were identified as the areas that expressed highly
      correlated temporal responses with the LRM derived from an independent group of
      subjects. RESULTS: Compared with an antonym generation task-based fMRI, the movie
      watching fMRI generated language maps with more localized activations in the left
      frontal language area, larger activations in the left temporoparietal language
      area, and significant activations in their right-hemisphere homologues. Results
      of 2 brain tumor patients' movie-watching fMRI using the LRM derived from the
      healthy subjects indicated its ability to map putative language areas; while
      their task-based fMRI maps were less robust and noisier. CONCLUSIONS: These
      results suggest that it is feasible to use this novel "task-free" paradigm as a
      complementary tool for fMRI language mapping when patients cannot perform the
      tasks. Its deployment in more neurosurgical patients and validation against gold
      standard techniques need further investigation.

PMID- 25962955
TI  - Capture-recapture approaches and the surveillance of livestock diseases: A
      review.
AB  - In disease surveillance, capture-recapture approaches have been used to estimate
      the frequency of endemic diseases monitored by imperfect surveillance systems. A
      standard output of these techniques is an estimate of the sensitivity of the
      surveillance. In addition, capture-recapture applications contribute to a better
      understanding of the disease detection processes and of the relationships between
      different surveillance data sources, and help identify variables associated with
      the under-detection of diseases. Although capture-recapture approaches have long
      been used in public health, their application to livestock disease surveillance
      is only recent. In this paper, we review the different capture-recapture
      approaches applied in livestock disease surveillance, and discuss their benefits
      and limitations in the light of the characteristics of the surveillance and
      control practices used in animal health. 

PMID- 25962956
TI  - The potential of canine sentinels for reemerging Trypanosoma cruzi transmission.
AB  - BACKGROUND: Chagas disease, a vector-borne disease transmitted by triatomine bugs
      and caused by the parasite Trypanosoma cruzi, affects millions of people in the
      Americas. In Arequipa, Peru, indoor residual insecticide spraying campaigns are
      routinely conducted to eliminate Triatoma infestans, the only vector in this
      area. Following insecticide spraying, there is risk of vector return and
      reinitiation of parasite transmission. Dogs are important reservoirs of T. cruzi
      and may play a role in reinitiating transmission in previously sprayed areas.
      Dogs may also serve as indicators of reemerging transmission. METHODS: We
      conducted a cross-sectional serological screening to detect T. cruzi antibodies
      in dogs, in conjunction with an entomological vector collection survey at the
      household level, in a disease endemic area that had been treated with insecticide
      13 years prior. Spatial clustering of infected animals and vectors was assessed
      using Ripley's K statistic, and the odds of being seropositive for dogs proximate
      to infected colonies was estimated with multivariate logistic regression.
      RESULTS: There were 106 triatomine-infested houses (41.1%), and 45 houses
      infested with T. cruzi-infected triatomine insects (17.4%). Canine seroprevalence
      in the area was 12.3% (n=154); all seropositive dogs were 9 months old or older.
      We observed clustering of vectors carrying the parasite, but no clustering of
      seropositive dogs. The age- and sex-adjusted odds ratio between seropositivity to
      T. cruzi and proximity to an infected triatomine (<=50m) was 5.67 (95% CI: 1.12
      28.74; p=0.036). CONCLUSIONS: Targeted control of reemerging transmission can be
      achieved by improved understanding of T. cruzi in canine populations. Our results
      suggest that dogs may be useful sentinels to detect re-initiation of transmission
      following insecticide treatment. Integration of canine T. cruzi blood sampling
      into existing interventions for zoonotic disease control (e.g., rabies
      vaccination programs) can be an effective method of increasing surveillance and
      improving understanding of disease distribution.

PMID- 25962957
TI  - Endogenous molecular network reveals two mechanisms of heterogeneity within
      gastric cancer.
AB  - Intratumor heterogeneity is a common phenomenon and impedes cancer therapy and
      research. Gastric cancer (GC) cells have generally been classified into two
      heterogeneous cellular phenotypes, the gastric and intestinal types, yet the
      mechanisms of maintaining two phenotypes and controlling phenotypic transition
      are largely unknown. A qualitative systematic framework, the endogenous molecular
      network hypothesis, has recently been proposed to understand cancer genesis and
      progression. Here, a minimal network corresponding to such framework was found
      for GC and was quantified via a stochastic nonlinear dynamical system. We then
      further extended the framework to address the important question of intratumor
      heterogeneity quantitatively. The working network characterized main known
      features of normal gastric epithelial and GC cell phenotypes. Our results
      demonstrated that four positive feedback loops in the network are critical for GC
      cell phenotypes. Moreover, two mechanisms that contribute to GC cell
      heterogeneity were identified: particular positive feedback loops are responsible
      for the maintenance of intestinal and gastric phenotypes; GC cell progression
      routes that were revealed by the dynamical behaviors of individual key components
      are heterogeneous. In this work, we constructed an endogenous molecular network
      of GC that can be expanded in the future and would broaden the known mechanisms
      of intratumor heterogeneity. 

PMID- 25962958
TI  - Involvement of Ras GTPase-activating protein SH3 domain-binding protein 1 in the
      epithelial-to-mesenchymal transition-induced metastasis of breast cancer cells
      via the Smad signaling pathway.
AB  - In situ models of epithelial-to-mesenchymal transition (EMT)-induced carcinoma
      develop into metastatic carcinoma, which is associated with drug resistance and
      disease recurrence in human breast cancer. Ras GTPase-activating protein SH3
      domain-binding protein 1 (G3BP1), an essential Ras mediator, has been implicated
      in cancer development, including cell growth, motility, invasion and apoptosis.
      Here, we demonstrated that the upregulation of G3BP1 activates the EMT in breast
      cancer cells. Silencing Smads almost completely blocked this G3BP1-induced EMT,
      suggesting that this process depends on the Smad signaling pathway. We also found
      that G3BP1 interacted with the Smad complex. Based on these results, we proposed
      that G3BP1 might act as a novel co-factor of Smads by regulating their
      phosphorylation status. Moreover, knockdown of G3BP1 suppressed the mesenchymal
      phenotype of MDA-MB-231 cells in vitro and suppressed tumor growth and lung
      metastasis of 4T1 cells in vivo. Our findings identified a novel function of
      G3BP1 in the progression of breast cancer via activation of the EMT, indicating
      that G3BP1 might represent a potential therapeutic target for metastatic human
      breast cancer. 

PMID- 25962959
TI  - Cyclin-dependent kinase inhibitor dinaciclib potently synergizes with cisplatin
      in preclinical models of ovarian cancer.
AB  - Ovarian cancer is one of the most lethal of woman cancers, and its clinical
      therapeutic outcome currently is unsatisfied. Dinaciclib, a novel small molecule
      inhibitor of CDK1, CDK2, CDK5 and CDK9, is assessed in clinical trials for the
      treatment of several types of cancers. In this study, we investigated the
      anticancer effects and mechanisms of dinaciclib alone or combined with cisplatin
      in ovarian cancer. Dinaciclib alone actively induced cell growth inhibition, cell
      cycle arrest and apoptosis with the increased intracellular ROS levels, which
      were accompanied by obvious alterations of related proteins such as CDKs,
      Cyclins, Mcl-1, XIAP and survivin. Pretreatment with N-acety-L-cysteine
      significantly blocked ROS generation but only partially rescued apoptosis
      triggered by dinaciclib. Moreover, the combination of dinaciclib with cisplatin
      synergistically promoted cell cycle arrest and apoptosis, and inhibited the
      subcutaneous xenograft growth of ovarian cancer in nude mice. Altogether,
      dinaciclib potently synergizes with cisplatin in preclinical models of ovarian
      cancer, indicating this beneficial combinational therapy may be a promising
      strategy for treatment of ovarian cancer. 

PMID- 25962960
TI  - Prognostic significance of the TREK-1 K2P potassium channels in prostate cancer.
AB  - BACKGROUND: TREK-1 channels belong to the two-pore domain potassium channel
      superfamily and play an important role in central nervous system diseases.
      However, few studies have examined their role in carcinogenesis. METHODS: In this
      study, we assessed the expression of TREK-1 in 100 prostate cancer (PCa) tissues
      using immunohistochemistry and further analyzed its clinicopathological
      significance. Next, cell proliferation and cell cycle analysis were carried out
      on human PCa PC-3 cell lines where TREK-1 was stably knockdown. RESULTS: We found
      that compared with normal prostate tissues, PCa tissues showed overexpressed TREK
      1 levels and TREK-1 levels were positively associated with Gleason score and T
      staging. High level of TREK-1 expression was related to shorter castration
      resistance free survival (CRFS). Furthermore, knockdown of TREK-1 significantly
      inhibited PCa cell proliferation in vitro and in vivo, and induced a G1/S cell
      cycle arrest. CONCLUSIONS: Our results suggest that TREK-1 might be a biomarker
      in CRFS judgment of PCa, as well as a potential therapeutic target.

PMID- 25962962
TI  - Autologous osteochondral transplantation for osteochondral lesions of the talus
      in an athletic population.
AB  - PURPOSE: To assess clinical outcomes and return to sport in an athletic
      population treated with autologous osteochondral transplantation (AOT) for
      osteochondral lesions of the talus. METHODS: A total of 36 patients were included
      in this retrospective study including 21 professional athletes and 15 amateur
      athletes who participated in regular moderate- or high-impact athletic activity.
      All patients underwent autologous osteochondral transplantation of the talus
      under the care of a single surgeon. At a mean follow-up of 5.9 years, patients
      were assessed using the American Orthopaedic Foot and Ankle Society (AOFAS)
      scoring system. All patients also received pre-operative MRI with the follow-up
      MRI performed at 1 year and underwent assessment of return to athletic activity.
      RESULTS: The overall AOFAS score improved from 65.5 (SD +/- 11.1) to 89.4 (SD +/-
      14.4) (p = 0.01). At a final follow-up, 90% of professional athletes (19 of 21)
      were still competing in athletic activity or still able to participate in
      unrestricted activity. Of the recreational athletes, 87% (13 of 15) had full
      return to pre-injury activity levels, while two (13%) returned to activity with
      restrictions or reduced intensity. MRI showed cystic change in 33% of patients
      post-operatively; however, this did not appear to affect outcomes (n.s.). Donor
      site symptoms were seen in 11% of the cohort at final follow-up, despite high
      function at donor knee. CONCLUSION: The results of our study indicate that AOT
      procedure is able to achieve good outcomes in an athletic population at a midterm
      follow-up. LEVEL OF EVIDENCE: Retrospective case series, Level IV.

PMID- 25962961
TI  - Deubiquitinating enzymes as oncotargets.
AB  - Carcinogenesis is a complex process tightly regulated at multiple levels by post
      translational modifications. Epigenetics plays a major role in cancer
      development, all stable changes to the gene expression process that are not a
      result of a direct change in the DNA code are described as epigenetics.
      Epigenetic processes are regulated by post-translational modifications including
      ubiquitination which can directly affect either histones or transcription factors
      or may target their co-factors and interacting partners exerting an indirect
      effect. Deubiquitination of these target proteins is equally important and
      alterations in this pathway can also lead to cancer development, progression and
      metastasis. Only the correct, unaltered balance between ubiquitination and
      deubiquitination ensures healthy cellular homeostasis. In this review we focus on
      the role of deubiquitinating (DUB) enzymes in various aspects of epigenetics
      including the regulation of transcription factors, histone modifications, DNA
      damage repair pathways and cell cycle regulation. We discuss the impact of those
      processes on tumourigenesis and potential therapeutic applications of DUBs for
      cancer treatment. 

PMID- 25962964
TI  - Regulatory T cells and potential inmmunotherapeutic targets in lung cancer.
AB  - Lung cancer and metastasis are two of the most lethal diseases globally and
      seldom have effective therapies. Immunotherapy is considered as one of the
      powerful alternatives. Regulatory T cells (Tregs) can suppress the activation of
      the immune system, maintain immune tolerance to self-antigens, and contribute to
      immunosuppression of antitumor immunity, which is critical for tumor immune
      evasion in epithelial malignancies, including lung cancer. The present review
      gives an overview of the biological functions and regulations of Tregs associated
      with the development of lung cancer and metastasis and explores the potentials of
      Treg-oriented therapeutic targets. Subsets and features of Tregs mainly include
      naturally occurring Tregs (nTregs) (CD4(+) nTregs and CD8(+) nTregs) and
      adaptive/induced Tregs (CD4(+) iTregs and CD8(+) iTregs). Tregs, especially in
      circulation or regional lymph nodes, play an important role in the progress and
      metastasis of lung cancer and are considered as therapeutic targets and
      biomarkers to predict the survival length and recurrence of lung cancer.
      Increasing understanding of Tregs' functional mechanisms will lead to a number of
      clinical trials on the discovery and development of Treg-oriented new therapies.
      Tregs play important roles in lung cancer and metastasis, and the understanding
      of Tregs becomes more critical for clinical applications and therapies. Thus,
      Tregs and associated factors can be potential therapeutic targets for lung cancer
      immunotherapy. 

PMID- 25962963
TI  - Complex function of the knee joint: the current understanding of the knee.
AB  - Since the early years of orthopaedics, it is a well-known fact that anatomy
      follows function. During the evolution of mankind, the knee has been optimally
      adapted to the forces and loads acting at and through the knee joint. However,
      anatomy of the knee joint is variable and the only constant is its complex
      function. In contrast to the time of open surgery, nowadays the majority of
      reconstructive knee surgery is done arthroscopically. Keyhole surgery is less
      invasive, but on the backside, the knee surgeon lacks daily visualisation of the
      complex open anatomy. As open anatomical knowledge is less present in our daily
      practice, it is even more important to highlight this complex anatomy and
      function of the knee. It is the purpose of this review to perform a systematic
      review of knee anatomy, highlight the complex function of the knee joint and
      present an overview about recent and current knowledge about knee function. Level
      of evidence Systematic review, Level IV. 

PMID- 25962965
TI  - Binding study advice: effect of raising the standards?

PMID- 25962966
TI  - The rationale for and use of assessment frameworks: improving assessment and
      reporting quality in medical education.
AB  - An assessment framework provides a structured conceptual map of the learning
      outcomes of a programme of study along with details of how achievement of the
      outcomes can be measured. The rationale for using frameworks to underpin the
      targeting of essential content components is especially relevant for the medical
      education community. Frameworks have the capacity to improve validity and
      reliability in assessment, allowing test developers to more easily create robust
      assessment instruments. The framework used by the Australian Medical Assessment
      Collaboration (AMAC) is an interesting and relevant case study for the
      international community as it draws and builds on established processes in higher
      education assessment. The AMAC experience offers an insight into important
      considerations for designing assessment frameworks and implementing frameworks in
      differing contexts. There are lessons which have the potential to improve
      assessment and reporting practice and quality in not only medical education, but
      in other domains of assessment. Prior to implementing any programme of
      assessment, the framework considerations outlined here will hopefully improve the
      quality of assessment and reporting practice by making implicit assumptions
      explicit, and allowing more critical reflection and evaluation throughout
      assessment processes. 

PMID- 25962967
TI  - Feedback on role model behaviour: effective for clinical trainers?
AB  - AIM: The aim of this study was to assess changes in role model behaviour of
      clinical trainers after giving personal feedback. METHODS: First-year general
      practitioner (GP) trainees at two institutes for GP speciality training in the
      Netherlands were asked to complete an assessment of their clinical trainers: the
      Role Model Apperception Tool (RoMAT). The RoMAT consists of attributes of
      positive role modelling divided into two components (Caring Attitude and
      Effectiveness) and was scored on a 5-point Likert scale twice. After the first
      assessment moment, the trainers received their personal scores combined with the
      mean score of their peers. The trainers were divided into three performance
      groups: below average, average and above average. RESULTS: Only the group with
      the lowest scores showed an improvement on the Effectiveness component of the
      RoMAT from 3.89 to 4.08 (p = 0.04) with an effect size of.52, showing a large
      effect. This pattern is confirmed by the number of trainers shifting from the
      below average performance group to the average (7) and above average (5)
      performance groups. CONCLUSION: Giving feedback to clinical trainers resulted in
      better scores on the Effectiveness characteristics. This indicates that role
      model behaviour of clinical trainers can be improved.

PMID- 25962968
TI  - Canine cutaneous melanocytic tumours: significance of beta-catenin and survivin
      immunohistochemical expression.
AB  - BACKGROUND: Recent investigations have highlighted the controversial role of
      Wnt/beta-catenin pathway activation in human cutaneous melanoma. Survivin has
      been proposed as a valid prognostic marker for invasive and metastatic melanomas
      and lymph node melanoma metastasis in human cutaneous melanoma and is a promising
      therapeutic target. HYPOTHESIS/OBJECTIVES: Our aim was to investigate the
      immunohistochemical expression of survivin and beta-catenin in canine cutaneous
      melanocytic tumours, in order to understand their prognostic significance.
      METHODS: Twenty-one melanocytic tumours (10 melanocytomas and 11 melanomas) were
      investigated by immunohistochemistry using specific anti-survivin and anti-beta
      catenin antibodies. A semi-quantitative method was used to analyse the results;
      beta-catenin immunolabelling in neoplastic cells was evaluated as cytoplasmic,
      membranous or nuclear. The number of survivin-positive cells was counted within
      ~1000 neoplastic cells. Results were related to histopathological features,
      evaluated in haematoxylin- and eosin-stained slides, and to the clinical data
      obtained through a telephone survey with referring veterinarians. RESULTS:
      Despite a low level of expression in the majority of cases, beta-catenin was
      found to be correlated strongly with malignant behaviour (P < 0.01). An
      overexpression of nuclear survivin was statistically related to histological
      features of malignancy, presence of metastasis and death related to melanoma
      spread (P < 0.01). CONCLUSIONS AND CLINICAL IMPORTANCE: The low nuclear beta
      catenin expression, mainly found in metastatic cases, would indicate that beta
      catenin activation may have only limited importance in the development or
      progression of canine cutaneous melanoma. The correlation of nuclear survivin
      expression with malignancy would indicate that survivin is possibly a useful
      prognostic marker and therapeutic target in canine melanoma patients.

PMID- 25962970
TI  - Citric Acid Enhanced Copper Removal by a Novel Multi-amines Decorated Resin.
AB  - Cu removal by a novel multi-amines decorated resin (PAMD) from wastewater in the
      absence or presence of citric acid (CA) was examined. Adsorption capacity of Cu
      onto PAMD markedly increased by 186% to 5.07 mmol/g in the presence of CA, up to
      7 times of that onto four commercial resins under the same conditions. Preloaded
      and kinetic studies demonstrated adsorption of [Cu-CA] complex instead of CA site
      bridging and variations of adsorbate species were qualitatively illustrated. The
      interaction configuration was further studied with ESI-MS, FTIR, XPS and XANES
      characterizations. The large enhancement of Cu adsorption in Cu-CA bi-solutes
      systems was attributed to mechanism change from single-site to dual-sites
      interaction in which cationic or neutral Cu species (Cu(2+) and CuHL(0))
      coordinated with neutral amine sites and anionic complex species (CuL(-) and
      Cu2L2(2-)) directly interacted with protonated amine sites via electrostatic
      attraction, and the ratio of the two interactions was approximately 0.5 for the
      equimolar bi-solutes system. Moreover, commonly coexisting ions in wastewaters
      had no obvious effect on the superior performance of PAMD. Also, Cu and CA could
      be recovered completely with HCl. Therefore, PAMD has a great potential to
      efficiently remove heavy metal ions from wastewaters in the presence of organic
      acids. 

PMID- 25962969
TI  - Therapeutic Basis of Clinical Pain Modulation.
AB  - Pain is a hallmark of almost all bodily ailments and can be modulated by agents,
      including analgesics and anesthetics that suppress pain signals in the central
      nervous system. Defects in the modulatory systems, including the endogenous pain
      inhibitory pathways, are a major factor in the initiation and chronicity of pain.
      Thus, pain modulation is particularly applicable to the practice of medicine.
      This review summarizes the existing literature on pain modulation. Here, we
      critically reviewed the literature from PubMed on pain modulation published
      primarily within the past 5 years in high impact journals. Specifically, we have
      discussed important anatomical landmarks of pain modulation and outlined the
      endogenous networks and underlying mechanisms of clinically relevant pain
      modulatory methods. The Gate Control Theory is briefly presented with discussion
      on the capacity of pain modulation to cause both hyper- and hypoalgesia. An
      emphasis has been given to highlight key areas in pain research that, because of
      unanswered questions or therapeutic potential, merit additional scientific
      scrutiny. The information presented in this paper would be helpful in developing
      novel therapies, metrics, and interventions for improved patient management. 

PMID- 25962971
TI  - Proposal for methods of diagnosis of fish bone foreign body in the Esophagus.
AB  - OBJECTIVE: To investigate the methods of diagnosis of fish bone foreign body in
      the esophagus and suggest a diagnostic protocol. STUDY DESIGN: Prospective cohort
      study. METHODS: A prospective study was performed on 286 patients with a history
      of fish bone foreign body impaction. Among them, 88 patients had negative
      findings in the oral cavity and laryngopharynx. Subsequent radiologic assessment
      of these patients included plain radiography and computed tomography (CT). Sixty
      six patients showed positive findings in the esophagus, and an attempt was made
      to remove the obstruction using transnasal esophagoscopy. RESULTS: In 66
      patients, a fish bone foreign body was detected in the esophagus by CT. In
      contrast, plain radiography detected a foreign body in only 30 patients. The
      overall detection rate of plain radiography compared with CT for fish bones was
      45.5%. Plain radiography detected 35.9% of the simple type fish bones and 54.5%
      of the gill bone detected by CT. However, jaw bones had a detection rate of 100%
      with both methods. The fish bone foreign bodies were most commonly located in the
      upper esophagus (n=65, 98.5%), followed by the lower esophagus (n=1, 1.5%).
      CONCLUSION: CT is a useful method for identification of esophageal fish bone
      foreign bodies. Therefore, CT should be considered as the first-choice technique
      for the diagnosis of esophageal fish bone foreign body. LEVEL OF EVIDENCE: 4.

PMID- 25962972
TI  - Pragmatic characteristics of patient-reported outcome measures are important for
      use in clinical practice.
AB  - OBJECTIVES: Measures for assessing patient-reported outcomes (PROs) that may have
      initially been developed for research are increasingly being recommended for use
      in clinical practice as well. Although psychometric rigor is essential, this
      article focuses on pragmatic characteristics of PROs that may enhance uptake into
      clinical practice. STUDY DESIGN AND SETTING: Three sources were drawn on in
      identifying pragmatic criteria for PROs: (1) selected literature review including
      recommendations by other expert groups; (2) key features of several model public
      domain PROs; and (3) the authors' experience in developing practical PROs.
      RESULTS: Eight characteristics of a practical PRO include: (1) actionability
      (i.e., scores guide diagnostic or therapeutic actions/decision making); (2)
      appropriateness for the relevant clinical setting; (3) universality (i.e., for
      screening, severity assessment, and monitoring across multiple conditions); (4)
      self-administration; (5) item features (number of items and bundling issues); (6)
      response options (option number and dimensions, uniform vs. varying options, time
      frame, intervals between options); (7) scoring (simplicity and interpretability);
      and (8) accessibility (nonproprietary, downloadable, available in different
      languages and for vulnerable groups, and incorporated into electronic health
      records). CONCLUSION: Balancing psychometric and pragmatic factors in the
      development of PROs is important for accelerating the incorporation of PROs into
      clinical practice.

PMID- 25962973
TI  - Demonstration of Tightly Radiation-Controlled Molecular Switch Based on CArG
      Repeats by In Vivo Molecular Imaging.
AB  - PURPOSE: Promoters developed for radiogene therapy always show non-negligible
      transcriptional activities, even when cells are not irradiated. This study
      developed a tightly radiation-controlled molecular switch based on radiation
      responsive element (CArG) repeats for in vivo molecular imaging using the
      Cre/loxP system. PROCEDURES: Different numbers of CArG repeats were cloned as a
      basal promoter directly, and its pre- and postirradiation transcriptional
      activities were analyzed by luciferase assay. Nine CArG repeats (E9) were chosen
      for use as a radiation-controlled molecular switch for the Cre/loxP system, and
      the feasibility of the switch in vitro and in vivo was demonstrated by luciferase
      assay and bioluminescence imaging, respectively. RESULTS: The E9 promoter, which
      exhibits extremely low transcriptional activity, showed a 1.8-fold enhancement
      after irradiation with a clinical dose of 2 Gy. Both in vitro and in vivo results
      indicated that E9 is relatively inert but sufficient to trigger the Cre/loxP
      system. The luciferase activity of stable H1299/pSTOP-FLuc cells transfected with
      pE9-NLSCre and exposed to 2-Gy radiation can reach 44 % of that of the same cells
      transfected with pCMV-NLSCre and not subjected to irradiation. By contrast, no
      appreciable difference was observed in reporter gene expression in both
      H1299/pSTOPFluc cells and tumors transfected with pE4Pcmv-NLSCre before and after
      irradiation, because the strong basal transcriptional activity of the CMV
      promoter, which acts as a copartner of E4, masked the response of E4 to
      radiation. CONCLUSIONS: Our results provide detailed insight into CArG elements
      as a radiation-controlled molecular switch that can facilitate the development of
      radiogene therapy.

PMID- 25962974
TI  - Depigmentation and hypertrophic scars after application of a fluid lactic acid
      tattoo eraser.
AB  - BACKGROUND: Tattoo removal is often requested by patients. The gold standard is
      laser tattoo removal that can be time- and cost-intensive. Therefore, safe
      alternatives without lasers, pain, and scars would be desirable. OBJECTIVE: We
      wanted to address safety of chemical tattoo erasers. METHODS: We report a case of
      depigmentation and hypertrophic scars after use of a chemical tattoo eraser and
      searched the literature. RESULTS: Chemical tattoo erasers are not only used by
      physicians, but also nonmedical professionals such as beauticians, tattoo
      artists, and others. The case report we observed and other cases from the
      literature suggest that lactic acid based tattoo erasers are risky. Available
      safety data are unsufficient to recommend such procedure as an alternative to
      current laser therapy. CONCLUSIONS: Chemical tattoo erasers based on lactic acid
      may be capable to remove tattoo ink but the procedure bears safety risks of
      permanent adverse effects. For the safety of patients, better regulations for
      tattoo erasers need to be implemented. Patients need to be informed about adverse
      effects by such procedures.

PMID- 25962975
TI  - Cardiac resuscitation: No benefit of therapeutic hypothermia after cardiac arrest
      in children.

PMID- 25962977
TI  - Anticoagulation therapy: Bleeding no worse with novel agents.

PMID- 25962979
TI  - Genetics: CAD genetic risk helps predict SCD.

PMID- 25962976
TI  - Cardiotoxicity of anticancer treatments.
AB  - Patients with cancer can experience adverse cardiovascular events secondary to
      the malignant process itself or its treatment. Patients with cancer might also
      have underlying cardiovascular illness, the consequences of which are often
      exacerbated by the stress of the tumour growth or its treatment. With the advent
      of new treatments and subsequent prolonged survival time, late effects of cancer
      treatment can become clinically evident decades after completion of therapy. The
      heart's extensive energy reserve and its ability to compensate for reduced
      function add to the complexity of diagnosis and timely initiation of therapy.
      Additionally, modern oncological treatment regimens often incorporate multiple
      agents whose deleterious cardiac effects might be additive or synergistic.
      Treatment-related impairment of cardiac contractility can be either transient or
      irreversible. Furthermore, cancer treatment is associated with life-threatening
      arrhythmia, ischaemia, infarction, and damage to cardiac valves, the conduction
      system, or the pericardium. Awareness of these processes has gained prominence
      with the arrival of strategies to monitor and to prevent or to mitigate the
      effects of cardiovascular damage. A greater understanding of the mechanisms of
      injury can prolong the lives of those cured of their malignancy, but left with
      potentially devastating cardiac sequelae. 

PMID- 25962978
TI  - Epigenetic modifications and noncoding RNAs in cardiac hypertrophy and failure.
AB  - The regulatory networks governing gene expression in cardiomyocytes are under
      intense investigation, not least because dysregulation of the gene programme has
      a fundamental role in the development of a failing myocardium. Epigenetic
      modifications and functional non-protein-coding RNAs (ncRNAs) are important
      contributors to this process. The epigenetic modifications that regulate
      transcription comprise post-translational changes to histones-the proteins around
      which DNA is wound-as well as modifications to cytosine residues on DNA. The most
      studied of the histone changes are acetylation and methylation. Histone
      acetylation is known to be important in cardiac physiology and pathophysiology,
      but the roles of other histone modifications and of cytosine methylation are only
      starting to be investigated. Understanding of the role of microRNAs has also seen
      major advancements, but the function of long ncRNAs is less well defined.
      Moreover, the connection between ncRNAs and epigenetic modifications is poorly
      understood in the heart. In this Review, we summarize new insights into how these
      two layers of gene-expression regulation might be involved in the pathogenesis of
      cardiac hypertrophy and failure, and how we are only beginning to appreciate the
      complexity of the interactive network of which they are part. 

PMID- 25962980
TI  - Chemical Interactions of Polyethylene Glycols (PEGs) and Glycerol with Protein
      Functional Groups: Applications to Effects of PEG and Glycerol on Protein
      Processes.
AB  - In this work, we obtain the data needed to predict chemical interactions of
      polyethylene glycols (PEGs) and glycerol with proteins and related organic
      compounds and thereby interpret or predict chemical effects of PEGs on protein
      processes. To accomplish this, we determine interactions of glycerol and tetraEG
      with >30 model compounds displaying the major C, N, and O functional groups of
      proteins. Analysis of these data yields coefficients (alpha values) that quantify
      interactions of glycerol, tetraEG, and PEG end (-CH2OH) and interior (-CH2OCH2-)
      groups with these groups, relative to interactions with water. TetraEG (strongly)
      and glycerol (weakly) interact favorably with aromatic C, amide N, and cationic
      N, but unfavorably with amide O, carboxylate O, and salt ions. Strongly
      unfavorable O and salt anion interactions help make both small and large PEGs
      effective protein precipitants. Interactions of tetraEG and PEG interior groups
      with aliphatic C are quite favorable, while interactions of glycerol and PEG end
      groups with aliphatic C are not. Hence, tetraEG and PEG300 favor unfolding of the
      DNA-binding domain of lac repressor (lacDBD), while glycerol and di- and
      monoethylene glycol are stabilizers. Favorable interactions with aromatic and
      aliphatic C explain why PEG400 greatly increases the solubility of aromatic
      hydrocarbons and steroids. PEG400-steroid interactions are unusually favorable,
      presumably because of simultaneous interactions of multiple PEG interior groups
      with the fused ring system of the steroid. Using alpha values reported here,
      chemical contributions to PEG m-values can be predicted or interpreted in terms
      of changes in water-accessible surface area (DeltaASA) and separated from
      excluded volume effects. 

PMID- 25962981
TI  - Decreased levels of alpha-synuclein in cerebrospinal fluid of patients with
      clinically isolated syndrome and multiple sclerosis.
AB  - Cerebrospinal fluid (CSF) alpha-synuclein (ASYN) levels are emerging as a
      possible biomarker in a number of neurodegenerative conditions; however, there
      has been little study of such levels in demyelinating conditions with
      neurodegeneration such as multiple sclerosis (MS). In this study, we aimed to
      assess CSF ASYN levels in MS spectrum [clinically isolated syndrome (CIS) and MS]
      patients and compare them to those obtained in control subjects with benign
      neurological conditions (BNC). We used a recently developed, ultra-sensitive
      sandwich enzyme-linked immunosorbent assay to measure and compare CSF ASYN levels
      in three categories of subjects: BNC (n = 38), CIS (n = 36) and MS [Relapsing
      Remitting (RRMS, n = 22) and Primary Progressive (PPMS, n = 15)]. We also
      performed secondary analyses, including relationship of CSF ASYN levels to aging,
      gender, presence of CSF oligoclonal bands (OB) and gadolinium (Gd)-enhancing
      demyelinating lesions on T1-weighted MRIs. CSF ASYN levels were found to be
      significantly lower in the CIS (78.2 +/- 7.5 pg/mL), RRMS (76.8 +/- 5.1 pg/mL),
      and PPMS (76.3 +/- 6.7 pg/mL) groups compared to the BNC (125.7 +/- 13.6 pg/mL)
      group. Secondary analyses did not reveal additional correlations. Our results
      suggest that in a cohort of CIS and MS patients, CSF ASYN levels are decreased,
      thus providing another possible link between MS and neurodegeneration. Future
      studies will need to be performed to confirm and extend these findings, to lead
      to a fuller understanding of the possible biological link between ASYN and MS.
      Alpha-synuclein levels in the Cerebrosinal Fluid (CSF) may reflect
      neurodegenerative processes. Here we measure CSF alpha-synuclein in demyelinating
      conditions ranging from Clinically Isolated Syndrome to Primary Progressive
      Multiple Sclerosis (MS). We find a similar magnitude of decreased alpha-synuclein
      compared to a control group in all such MS spectrum conditions; such a decrease
      may reflect an underlying early neurodegenerative disease process.

PMID- 25962982
TI  - External stimulation-controllable heat-storage ceramics.
AB  - Commonly available heat-storage materials cannot usually store the energy for a
      prolonged period. If a solid material could conserve the accumulated thermal
      energy, then its heat-storage application potential is considerably widened. Here
      we report a phase transition material that can conserve the latent heat energy in
      a wide temperature range, T<530 K and release the heat energy on the application
      of pressure. This material is stripe-type lambda-trititanium pentoxide, lambda
      Ti3O5, which exhibits a solid-solid phase transition to beta-trititanium
      pentoxide, beta-Ti3O5. The pressure for conversion is extremely small, only 600
      bar (60 MPa) at ambient temperature, and the accumulated heat energy is
      surprisingly large (230 kJ L(-1)). Conversely, the pressure-produced beta
      trititanium pentoxide transforms to lambda-trititanium pentoxide by heat, light
      or electric current. That is, the present system exhibits pressure-and-heat,
      pressure-and-light and pressure-and-current reversible phase transitions. The
      material may be useful for heat storage, as well as in sensor and switching
      memory device applications. 

PMID- 25962983
TI  - Outbreak of Salmonella enterica serovar Typhimurium phage type DT41 in Danish
      poultry production.
AB  - Salmonella enterica subspecies enterica serovar Typhimurium (S. Typhimurium) is
      one of the most prevalent serovars in Europe - where both poultry and poultry
      related products are common sources of human salmonellosis. Due to efficient
      control programs, the prevalence of S. Typhimurium in Danish poultry production
      is very low. Despite this, during the past decades there has been a reoccurring
      problem with infections with S. Typhimurium phage type DT41 in the Danish poultry
      production without identifying a clear source. In the end of 2013 and beginning
      of 2014 an increased isolation of S. Typhimurium DT41 was noted mainly in this
      production, but also in other samples. To investigate this is in more detail, 47
      isolates from egg layers (n=5, 1 flock), broilers (n=33, 13 flocks), broiler
      breeding flocks and hatches (n=5; 2 flocks and 1 environmental hatchery sample),
      feed (n=1), poultry slaughter house (n=3, environmental sample and meat) were
      typed with multi locus variable number of tandem repeat analysis (MLVA) and
      pulsed-field gel electrophoresis (PFGE) to investigate the epidemiology of the
      outbreak. Based on PFGE results isolates were divided into four groups (Simpson's
      index of diversity (DI)=0.24+/-0.15). Due to the low DI, PFGE was not sufficient
      to provide information to unravel the outbreak. Based on MLVA typing the DT41
      (42/47 isolates) and the RDNC isolates (5/47) were split into nine groups
      (DI=0.65+/-0.14). When a maximum divergence at one locus was permitted these
      could be gathered into four groups. Using this criterion, combined with
      epidemiological information, a spread of one type from broiler breeders to
      broilers and further to the poultry slaughter house was plausible. In conclusion,
      although it could be concluded that a spread within the broiler production
      pyramid had taken place the source of the sudden increase of S. Typhimurium DT41
      remains unclear. To investigate this in more detail, further studies using whole
      genome sequencing to obtain a higher discriminatory strength and including
      isolates from a longer period of time and from various sources are in progress. 

PMID- 25962984
TI  - Alginate biomaterial for the treatment of myocardial infarction: Progress,
      translational strategies, and clinical outlook: From ocean algae to patient
      bedside.
AB  - Alginate biomaterial is widely utilized for tissue engineering and regeneration
      due to its biocompatibility, non-thrombogenic nature, mild and physical gelation
      process, and the resemblance of its hydrogel matrix texture and stiffness to that
      of the extracellular matrix. In this review, we describe the versatile biomedical
      applications of alginate, from its use as a supporting cardiac implant in
      patients after acute myocardial infarction (MI) to its employment as a vehicle
      for stem cell delivery and for the controlled delivery and presentation of
      multiple combinations of bioactive molecules and regenerative factors into the
      heart. Preclinical and first-in-man clinical trials are described in details,
      showing the therapeutic potential of injectable acellular alginate implants to
      inhibit the damaging processes after MI, leading to myocardial repair and tissue
      reconstruction. 

PMID- 25962985
TI  - Serine enantiomers as diagnostic biomarkers for schizophrenia and bipolar
      disorder.

PMID- 25962986
TI  - Determinants of Regional Variation in Health Expenditures in Germany.
AB  - Health care expenditure in Germany shows clear regional differences. Such
      geographic variations are often seen as an indicator for inefficiency. With its
      homogeneous health care system, low co-payments and uniform prices, Germany is a
      particularly suited example to analyse regional variations. We use data for the
      year 2011 on expenditure, utilization of health services and state of health in
      Germany's statutory health insurance system. This data, which originate from a
      variety of administrative sources and cover about 90% of the population, are
      enriched with a wealth of socio-economic variables, data on pollutants, prices
      and individual preferences. State of health and demography explains 55% of the
      differences as measured by the standard deviation while all control variables
      account for a total of 72% of the differences at county level. With other
      measures of variation, we can account for an even greater proportion. A higher
      proportion of variation than usually supposed can thus be explained. Whilst this
      study cannot quantify inefficiencies, our results contradict the thesis that
      regional variations reflect inefficiency. Copyright (c) 2015 John Wiley & Sons,
      Ltd.

PMID- 25962987
TI  - Characterization of the pathogenome and phylogenomic classification of
      enteropathogenic Escherichia coli of the O157:non-H7 serotypes.
AB  - Escherichia coli of the O157 serogroup are comprised of a diverse collection of
      more than 100 O157:non-H7 serotypes that are found in the environment, animal
      reservoir and infected patients and some have been linked to severe outbreaks of
      human disease. Among these, the enteropathogenic E. coli O157:non-H7 serotypes
      carry virulence factors that are hallmarks of enterohemorrhagic E. coli, such as
      causing attaching and effacing lesions during human gastrointestinal tract
      infections. Given the shared virulence gene pool between O157:H7 and O157:non-H7
      serotypes, our objective was to examine the prevalence of virulence traits of
      O157:non-H7 serotypes within and across their H-serotype and when compared to
      other E. coli pathovars. We sequenced six O157:non-H7 genomes complemented by
      four genomes from public repositories in an effort to determine their virulence
      state and genetic relatedness to the highly pathogenic enterohemorrhagic O157:H7
      lineage and its ancestral O55:H7 serotype. Whole-genome-based phylogenomic
      analysis and molecular typing is indicative of a non-monophyletic origin of the
      heterogeneous O157:non-H7 serotypes that are only distantly related to the
      O157:H7 serotype. The availability of multiple genomes enables robust
      phylogenomic placement of these strains into their evolutionary context, and the
      assessment of the pathogenic potential of the O157:non-H7 strains in causing
      human disease. 

PMID- 25962988
TI  - Value of C-Arm Computed Tomography to Evaluate Stent Deployment During Femoro
      Popliteal Revascularization.
AB  - PURPOSE: To compare the accuracy of C-arm computed tomography (CT) and digital
      subtraction angiography (DSA) in detecting incomplete stent expansion (ISE) after
      superficial femoral artery (SFA) stenting using intravascular ultrasound (IVUS)
      as a gold standard. MATERIALS: Fifty patients with symptomatic SFA occlusive
      disease requiring angioplasty were prospectively included. Once technical success
      (<30 % residual stenosis) was obtained on post-procedural DSA, C-arm CT and IVUS
      were acquired. DSA and C-arm CT examinations were reviewed by 2 investigators and
      correlated with IVUS. C-arm CT image quality was rated on a four-point scale.
      Doppler ultrasound was performed at 1-year follow-up. RESULTS: The ankle-brachial
      index was 0.69 +/- 0.10 and 0.99 +/- 0.40, respectively, pre- and post-procedure.
      C-arm CT imaging quality was rated as good or excellent in 80%. In-stent minimal
      luminal diameter (MLD) was evaluated at 4.71 +/- 0.7 mm on DSA, 3.39 +/- 0.6 mm
      on IVUS, and 3.12 +/- 0.9 mm on C-arm CT. Compared to IVUS, DSA demonstrated an
      overestimation of MLD (p = 0.0001), an underestimation of ISE (DSA = 18.8% +/-
      7.6; IVUS = 29.8% +/- 9) (p < 0.0001), and a poor inter-technique intra-class
      correlation coefficient (ICC = 0.24). No difference was observed between IVUS and
      C-arm CT in ISE as calculated by diameter (29.8 +/- 9 vs. 28.2 +/- 12.5%, p =
      0.5) and area (30.2 +/- 8.4 vs. 33.3 +/- 9.5%, p = 0.2). Inter-technique ICC
      between C-arm CT and IVUS was 0.72 [95%CI 0.49; 0.85] for MLA measurements. The
      inter-observer ICC for MLD and MLA measurements on C-arm CT were, respectively,
      estimated at 0.75 [95% CI 0.40, 0.89] and 0.77 [95% CI 0.43, 0.90)]. CONCLUSIONS:
      C-arm CT presents a better correlation with IVUS than DSA to determine lumen
      diameter and ISE immediately after percutaneous revascularization.

PMID- 25962989
TI  - Objective Measurement of Arterial Flow Before and After Transcatheter Arterial
      Chemoembolization: A Feasibility Study Using Quantitative Color-Coding Analysis.
AB  - PURPOSE: To quantitatively measure the hemodynamic change of hepatic artery
      before and after transcatheter arterial chemoembolization (TACE) of
      hepatocellular carcinoma (HCC) by quantitative color-coding analysis (QCA).
      MATERIALS AND METHODS: This prospective study registered 64 consecutive HCC
      patients who underwent segmental or subsegmental TACE with epirubicin and
      lipiodol at level 2 or 3 of the subjective angiographic chemoembolization
      endpoint. QCA was used to determine the maximal density time (T(max)) of selected
      intravascular region of interest (ROI). Relative T(max) (rT(max)) was defined as
      the T(max) at the selected ROI minus the time of contrast medium spurting from
      the catheter tip. The rT(max) of hepatic arteries was analyzed before and after
      embolization. RESULTS: The pre- and post-treatment rT(max) of the landmarks at
      the treated segmental artery were 1.96 +/- 0.48 and 3.14 +/- 1.77 s, p < 0.001.
      According to the treated lobe, 30 patients were treated for the right lobe alone,
      and 8 patients were treated for the left lobe alone. The pre- and post-rT(max) of
      treated segmental artery were 2.06 +/- 0.54, 3.34 +/- 1.63 s, p < 0.001 and 1.89
      +/- 0.45, 2.68 +/- 1.46 s, p = 0.12, respectively. The rT(max) of the proximal
      lobar hepatic arteries or proper hepatic artery had no significant change before
      and after TACE. CONCLUSIONS: The QCA is feasible to quantify embolization
      endpoints by comparing the rT(max) in selected hepatic arteries before and after
      TACE. The rT(max) of treated segmental artery was significant prolonged after
      optimized procedures.

PMID- 25962990
TI  - Use of a New Hybrid Heparin-Bonded Nitinol Ring Stent in the Popliteal Artery:
      Procedural and Mid-term Clinical and Anatomical Outcomes.
AB  - PURPOSE: To report the immediate and mid-term clinical and anatomical outcomes of
      a novel, hybrid, heparin-bonded, nitinol ring stent (TIGRIS; Gore Medical) when
      used for the treatment of lesions located in the popliteal artery. MATERIALS AND
      METHODS: This was a prospective single-centre registry. Patients eligible for
      inclusion were individuals suffering from symptomatic popliteal arterial
      occlusive disease (Rutherford-Becker stage 3-6; P1-P3 segments) and treated with
      placement of the TIGRIS stent(s). Patients were prospectively scheduled for
      clinical review and duplex ultrasound follow-up after 6 and 12 months. Outcome
      measures included immediate technical success, primary vessel patency, in-stent
      binary restenosis (evaluable by Duplex at 50 % threshold; PSVR > 2.0), freedom
      from target lesion revascularization (TLR) and amputation-free survival (AFS)
      estimated by Kaplan-Meier (K-M) survival analysis. Cox proportional-hazards
      regression analysis was also performed to adjust for confounders and search for
      independent predictors of outcomes. RESULTS: From August 2012 to March 2014, a
      total of 54 popliteal TIGRIS stents were implanted in 50 limbs of 48 patients (27
      men and 21 women; mean age 76.0 +/- 1.7 years). Median Rutherford-Becker stage
      was five at baseline and 37/50 (74.0%) were chronic total occlusions. Technical
      success was achieved in all cases (100%). Stented lesion length was 114.2 +/-
      36.9 mm (range 6-20 cm). Median follow-up was 11.8 +/- 0.8 months. After 12
      months, primary patency of the TIGRIS stent was 69.5 +/- 10.2% with an 86.1 +/-
      5.9% freedom from TLR and 87 +/- 5.0% AFS (K-M estimates). CONCLUSION: The TIGRIS
      hybrid heparin-bonded nitinol ring stent is a safe and effective endovascular
      option for complex occlusive disease of the popliteal artery.

PMID- 25962991
TI  - Pelvic Arterial Anatomy Relevant to Prostatic Artery Embolisation and Proposal
      for Angiographic Classification.
AB  - PURPOSE: To describe and categorize the angiographic findings regarding prostatic
      vascularization, propose an anatomic classification, and discuss its implications
      for the PAE procedure. METHODS: Angiographic findings from 143 PAE procedures
      were reviewed retrospectively, and the origin of the inferior vesical artery
      (IVA) was classified into five subtypes as follows: type I: IVA originating from
      the anterior division of the internal iliac artery (IIA), from a common trunk
      with the superior vesical artery (SVA); type II: IVA originating from the
      anterior division of the IIA, inferior to the SVA origin; type III: IVA
      originating from the obturator artery; type IV: IVA originating from the internal
      pudendal artery; and type V: less common origins of the IVA. Incidences were
      calculated by percentage. RESULTS: Two hundred eighty-six pelvic sides (n = 286)
      were analyzed, and 267 (93.3%) were classified into I-IV types. Among them, the
      most common origin was type IV (n = 89, 31.1%), followed by type I (n = 82,
      28.7%), type III (n = 54, 18.9%), and type II (n = 42, 14.7%). Type V anatomy was
      seen in 16 cases (5.6%). Double vascularization, defined as two independent
      prostatic branches in one pelvic side, was seen in 23 cases (8.0%). CONCLUSIONS:
      Despite the large number of possible anatomical variations of male pelvis, four
      main patterns corresponded to almost 95% of the cases. Evaluation of anatomy in a
      systematic fashion, following a standard classification, will make PAE a faster,
      safer, and more effective procedure.

PMID- 25962992
TI  - Minimizing Hypoglycemia and Weight Gain with Intensive Glucose Control: Potential
      Benefits of a New Combination Therapy (IDegLira).
AB  - Due to the progressive nature of type 2 diabetes (T2D), the majority of patients
      require increasing levels of therapy to achieve and maintain good glycemic
      control. At present, once patients become uncontrolled on oral antidiabetic
      therapies, the two primary treatment options are glucagon-like peptide-1 receptor
      agonists (GLP-1RAs) or basal insulin, although earlier use of GLP-1RAs has also
      been advocated. While both of these drug classes have proven efficacy in treating
      T2D, there can be limitations to their use in some patients, and resistance to
      further treatment intensification among both patients and physicians. More
      recently, treatment incorporating both a GLP-1RA and a basal insulin has been
      used successfully in the clinic and the first such combination product, IDegLira
      (insulin degludec+liraglutide), has recently been approved for use in Europe.
      IDegLira combines insulin degludec and the GLP-1RA liraglutide in a single
      injection. In both insulin-naive and basal insulin-treated individuals with T2D,
      IDegLira has demonstrated greater reductions in glycated hemoglobin (HbA1c) than
      either of the individual components, with a low rate of hypoglycemia and weight
      loss. IDegLira may provide a new option for patients requiring treatment
      intensification but for whom increased weight or a higher risk of hypoglycemia
      are barriers. This article discusses the rationale behind combining these two
      drug classes and reviews the available clinical evidence for the efficacy and
      safety of IDegLira.

PMID- 25962993
TI  - Minimally invasive Ivor-Lewis oesophagectomy is a feasible and safe approach for
      patients with oesophageal cancer.
AB  - BACKGROUND: Minimally invasive approaches are increasingly being used in
      oesophagectomy. The aim of this study was to compare the short-term clinical
      outcomes of the minimally invasive Ivor-Lewis oesophagectomy (MIILE) technique
      with those of the open Ivor-Lewis oesophagectomy (OILE) technique. METHODS: We
      identified 131 patients who underwent MIILE combined with thoracoscopy and
      laparoscopy. These patients were compared with 248 patients who underwent OILE
      between January 2012 and December 2013. RESULTS: MIILE and OILE produced similar
      post-operative hospital mortality (MIILE 2.3 versus OILE 2%; P = 1.000). The
      MIILE approach was associated with a significant decrease in the time until chest
      drain removal (MIILE 9.07 +/- 5.075 days versus OILE 11.26 +/- 6.989 days; P =
      0.002) and post-operative length of stay (MIILE 10.89 +/- 4.976 days versus OILE
      12.83 +/- 6.921 days; P = 0.002). Pneumonia was the most common complication in
      both groups. MIILE patients exhibited a lower incidence of post-operative
      pneumonia (MIILE 17.6% versus OILE 28.2%; P = 0.024) compared with OILE. The
      survival rate did not significantly differ between the MIILE and OILE groups (1
      year survival rates: MIILE 86 versus OILE 88.2%; P = 0.537). CONCLUSIONS: In this
      study, we demonstrate that MIILE is a feasible and safe approach for patients
      with middle or lower oesophageal cancer.

PMID- 25962994
TI  - Cranberry flavonoids prevent toxic rat liver mitochondrial damage in vivo and
      scavenge free radicals in vitro.
AB  - The present study was undertaken for further elucidation of the mechanisms of
      flavonoid biological activity, focusing on the antioxidative and protective
      effects of cranberry flavonoids in free radical-generating systems and those on
      mitochondrial ultrastructure during carbon tetrachloride-induced rat
      intoxication. Treatment of rats with cranberry flavonoids (7 mg/kg) during
      chronic carbon tetrachloride-induced intoxication led to prevention of
      mitochondrial damage, including fragmentation, rupture and local loss of the
      outer mitochondrial membrane. In radical-generating systems, cranberry flavonoids
      effectively scavenged nitric oxide (IC50  = 4.4 +/- 0.4 ug/ml), superoxide anion
      radicals (IC50  = 2.8 +/- 0.3 ug/ml) and hydroxyl radicals (IC50  = 53 +/- 4
      ug/ml). The IC50 for reduction of 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH)
      was 2.2 +/- 0.3 ug/ml. Flavonoids prevented to some extent lipid peroxidation in
      liposomal membranes and glutathione oxidation in erythrocytes treated with UV
      irradiation or organic hydroperoxides as well as decreased the rigidity of the
      outer leaflet of the liposomal membranes. The hepatoprotective potential of
      cranberry flavonoids could be due to specific prevention of rat liver
      mitochondrial damage. The mitochondria-addressed effects of flavonoids might be
      related both to radical-scavenging properties and modulation of various
      mitochondrial events.

PMID- 25962995
TI  - Preservation of the inferior alveolar neurovascular bundle in the osteotomy of
      benign lesions of the mandible using a digital template.
AB  - Our aim was to evaluate the effect of a digital template in the preservation of
      the inferior alveolar neurovascular bundle during osteotomy for benign lesions of
      the mandible in 6 patients who were treated with mandibular osteotomies during
      2013. Computed tomographic (CT) data were imported into ProPlan CMF 1.4 software.
      The borders of the lesion and the inferior alveolar canal were marked, and a
      digital template designed to mark the borders, outline the canal, and guide the
      osteotomy. A mirror image of the unaffected mandible was used to make a
      stereolithographic model by a rapid prototyping technique to prefabricate the
      reconstruction plate for the bone graft. The accuracy of the designs and the
      templates was evaluated during operation and postoperatively by CT. The sensation
      of the skin was tested using a Neurometer(r) CPT (current perception threshold)
      sensory detector (Neurotron Inc, Baltimore USA) to evaluate the function of the
      preserved inferior alveolar neurovascular bundle during follow up. With the
      digital template it was possible to guide removal of the bony lesion while
      accurately protecting the neurovascular bundle. Follow up for a mean of 8 months
      (range 5 -12) showed good facial symmetry, a stable occlusion, and recovery of
      sensation in the lower lip on the affected side. We conclude that a digital
      template can successfully help the resection of benign lesions of the mandible
      while preserving the function of the inferior alveolar neurovascular bundle. 

PMID- 25962996
TI  - Analysis of disruptive events and precarious situations caused by interaction
      with neurosurgical microscope.
AB  - BACKGROUND: Developments in micro-neurosurgical microscopes have improved
      operating precision and ensured the quality of outcomes. Using the stereoscopic
      magnified view, however, necessitates frequent manual adjustments to the
      microscope during an operation. METHOD: This article reports on an investigation
      of the interaction details concerning a state-of-the-art micro-neurosurgical
      microscope. The video data from detailed observations of neurosurgeons'
      interaction patterns with the microscope were analysed to examine disruptive
      events caused by adjusting the microscope. RESULTS: The primary findings show
      that interruptions caused by adjusting the microscope handgrips and mouth switch
      prolong the surgery time up to 10%. Surgeons, we observed, avoid interaction with
      the microscope's controls, settings, and configurations by working at the edge of
      the view, operating on a non-focused view, and assuming unergonomic body
      postures. CONCLUSIONS: The lack of an automatic method for adjusting the
      microscope is a major problem that causes interruptions during micro
      neurosurgery. From this understanding of disruptive events, we discuss the
      opportunities and limitations of interactive technologies that aim to reduce the
      frequency or shorten the duration of interruptions caused by microscope
      adjustment.

PMID- 25962997
TI  - Cloning, expression, and characterization of a Coxiella burnetii Cu/Zn Superoxide
      dismutase.
AB  - BACKGROUND: Periplasmically localized copper-zinc co-factored superoxide
      dismutase (SodC) enzymes have been identified in a wide range of Gram-negative
      bacteria and are proposed to protect bacteria from exogenously produced toxic
      oxygen radicals, which indicates the potential significance of a Coxiella
      burnetii SodC. RESULTS: Assays for SOD activity demonstrated that the cloned C.
      burnetii insert codes for a SOD that was active over a wide range of pH and
      inhibitable with 5 mM H2O2 and 1 mM sodium diethyldithiocarbamate, a
      characteristic of Cu/ZnSODs that distinguishes them from Fe or Mn SODs. The sodC
      was expressed by C. burnetii, has a molecular weight of approximately 18 kDa,
      which is consistent with the predicted molecular weight, and localized towards
      the periphery of C. burnetii. Over expression of the C. burnetii sodC in an E.
      coli sodC mutant restored resistance to H2O2 killing to wild type levels.
      CONCLUSIONS: We have demonstrated that C. burnetii does express a Cu/ZnSOD that
      is functional at low pH, appears to be excreted, and was able to restore H2O2
      resistance in an E. coli sodC mutant. Taken together, these results indicate that
      the C. burnetii Cu/ZnSOD is a potentially important virulence factor.

PMID- 25962998
TI  - A sample size planning approach that considers both statistical significance and
      clinical significance.
AB  - BACKGROUND: The CONSORT statement requires clinical trials to report confidence
      intervals, which help to assess the precision and clinical importance of the
      treatment effect. Conventional sample size calculations for clinical trials,
      however, only consider issues of statistical significance (that is, significance
      level and power). METHOD: A more consistent approach is proposed whereby sample
      size planning also incorporates information on clinical significance as indicated
      by the boundaries of the confidence limits of the treatment effect. RESULTS: The
      probabilities of declaring a "definitive-positive" or "definitive-negative"
      result (as defined by Guyatt et al., CMAJ 152(2):169-173, 1995) are controlled by
      calculating the sample size such that the lower confidence limit under H 1 and
      the upper confidence limit under H 0 are bounded by relevant cut-offs.
      Adjustments to the traditional sample size can be directly derived for the
      comparison of two normally distributed means in a test of nonequality, while
      simulations are used to estimate the sample size for evaluating the hazards ratio
      in a proportional-hazards model. CONCLUSIONS: This sample size planning approach
      allows for an assessment of the potential clinical importance and precision of
      the treatment effect in a clinical trial in addition to considerations of
      statistical power and type I error.

PMID- 25962999
TI  - Patient-specific characterization of the invasiveness and proliferation of low
      grade gliomas using serial MR imaging and a mathematical model of tumor growth.
AB  - Low-grade gliomas (LGGs) represent a significant proportion of hemispheric
      gliomas in adults. Although less aggressive than glioblastomas (GBMs), they have
      a broad range of biologic behavior, and often a limited prognosis. The aim of the
      present study was to explore LGG growth kinetics through a combination of routine
      MRI imaging and a novel adaptation of a mathematical tumor model. MRI imaging in
      14 retrospectively identified grade II LGGs that showed some tumor enhancement
      was used to assess tumor radii at two separate time-points. This information was
      combined with a reaction-diffusion partial-differential equation model of tumor
      growth to calculate diffusion (D) and proliferation (rho) coefficients for each
      tumor, representing measures of tumor invasiveness and cellular multiplication,
      respectively. The results were compared to previously published data on GBMs. The
      average value of D was 0.034 mm(2)/day and rho was 0.0056/day. Grade II LGGs had
      a broad range of D and rho. On average, the proliferation coefficient rho was
      significantly lower than previously published values for GBM, by about an order
      of magnitude. The diffusion coefficient, modeling invasiveness, however, was only
      slightly lower but without statistical significance. It was possible to calculate
      detailed growth kinetic parameters for some LGGs, potentially providing a new way
      to assess tumor aggressiveness and possibly gauge prognosis. Even within a single
      grade (WHO II), LGGs were found to have broad range of D and rho, possibly
      correlating to their variable biologic behavior. Overall, the model parameters
      suggest that LGG is less aggressive than GBM based primarily on a lower index of
      tumor proliferation rather than on lesser invasiveness.

PMID- 25963000
TI  - Accuracy of testosterone concentrations in compounded testosterone products.
AB  - OBJECTIVE: This study aims to evaluate the accuracy of the testosterone
      concentrations within testosterone gels and creams manufactured by compounding
      pharmacies. METHODS: Ten compounding pharmacies within Toronto area were
      included. Pharmacies were blinded as to the nature of the study. A standardized
      prescription for 50 mg of compounded testosterone gel/cream applied once daily
      was presented to each pharmacy. Two independently compounded batches were
      analyzed from each pharmacy 1 month apart. Testosterone concentrations in a 5-g
      sachet of Androgel(r) 1% (Abbott) and 5-g tube of Testim(r)1% (Auxilium) were
      evaluated as controls. Samples were analyzed independently and in a blinded
      fashion by the Laboratory Medicine Program at the University Health Network.
      Measurement of testosterone concentration was performed using a modified liquid
      chromatography tandem mass spectrometry validated for serum testosterone.
      RESULTS: Compounded formulations included seven gels and three creams with a
      volume/daily dose ranging from 0.2 mL to 1.25 mL. Product cost ranged from $57.32
      to $160.71 for a 30-day supply. There was significant variability both within and
      between pharmacies with respect to the measured concentration of testosterone in
      the compounded products. In contrast, the concentration of testosterone within
      Androgel and Testim was consistent and accurate. Collectively, only 50% (batch 1)
      and 30% (batch 2) of the compounding pharmacies provided a product with a
      testosterone concentration within +/- 20% of the prescribed dose. Two pharmacies
      compounded products with >20% of the prescribed dose. One pharmacy compounded a
      product with essentially no testosterone. CONCLUSIONS: Testosterone
      concentrations in compounded testosterone products can be variable and
      potentially compromise the efficacy and safety of treatment.

PMID- 25963001
TI  - Inappropriate Use of Radioactive Iodine for Low-Risk Papillary Thyroid Cancer Is
      Most Common in Regions with Poor Access to Healthcare.

PMID- 25963002
TI  - Strategies to decrease pertussis transmission to infants.
AB  - The Global Pertussis Initiative (GPI) is an expert scientific forum addressing
      the worldwide burden of pertussis, which remains a serious health issue,
      especially in infants. This age cohort is at risk for developing pertussis by
      transmission from those in close proximity. Risk is increased in infants aged 0
      to 6 weeks, as they are too young to be vaccinated. Older infants are at risk
      when their vaccination schedules are incomplete. Infants also bear the greatest
      disease burden owing to their high risk for pertussis-related complications and
      death; therefore, protecting them is a high priority. Two vaccine strategies have
      been proposed to protect infants. The first involves vaccinating pregnant women,
      which directly protects through the passive transfer of pertussis antibodies. The
      second strategy, cocooning, involves vaccinating parents, caregivers, and other
      close contacts, which indirectly protects infants from transmission by preventing
      disease in those in close proximity. The goal of this review was to present and
      discuss evidence on these 2 strategies. Based on available data, the GPI
      recommends vaccination during pregnancy as the primary strategy, given its
      efficacy, safety, and logistic advantages over a cocoon approach. If vaccination
      during pregnancy is not feasible, then all individuals having close contact with
      infants <6 months old should be immunized consistent with local health authority
      guidelines. These efforts are anticipated to minimize pertussis transmission to
      vulnerable infants, although real-world effectiveness data are limited. Countries
      should educate lay and medical communities on pertussis and introduce robust
      surveillance practices while implementing these protective strategies. 

PMID- 25963003
TI  - Inconclusive diagnosis of cystic fibrosis after newborn screening.
AB  - OBJECTIVES: To prospectively study infants with an inconclusive diagnosis of
      cystic fibrosis (CF) identified by newborn screening (NBS; "CF screen positive,
      inconclusive diagnosis" [CFSPID]) for disease manifestations. METHODS: Infants
      with CFSPID and CF based on NBS from 8 CF centers were prospectively evaluated
      and monitored. Genotype, phenotype, repeat sweat test, serum trypsinogen, and
      microbiology data were compared between subjects with CF and CFSPID and between
      subjects with CFSPID who did (CFSPID->CF) and did not (CFSPID->CFSPID) fulfill
      the criteria for CF during the first 3 years of life. RESULTS: Eighty-two
      subjects with CFSPID and 80 subjects with CF were enrolled. The ratio of CFSPID
      to CF ranged from 1:1.4 to 1:2.9 in different centers. CFTR mutation rates did
      not differ between groups; 96% of subjects with CFSPID and 93% of subjects with
      CF had 2 mutations. Subjects with CFSPID had significantly lower NBS
      immunoreactive trypsinogen (median [interquartile range]:77 [61-106] vs 144 [105
      199] MUg/L; P < .0001) than did subjects with CF. Pseudomonas aeruginosa and
      Stenotrophomonas maltophilia were isolated in 12% and 5%, respectively, of
      subjects with CFSPID. CF was diagnosed in 9 of 82 (11%) subjects with CFSPID
      (genotype and abnormal sweat chloride = 3; genotype alone = 4; abnormal sweat
      chloride only = 2). Sweat chloride was abnormal in CFSPID->CF patients at a mean
      (SD) age of 21.3 (13.8) months. CFSPID->CF patients had significantly higher
      serial sweat chloride (P < .0001) and serum trypsinogen (P = .009) levels than
      did CFSPID->CFSPID patients. CONCLUSIONS: A proportion of infants with CFSPID
      will be diagnosed with CF within the first 3 years. These findings underscore the
      need for clinical monitoring, repeat sweat testing at age 2 to 3 years, and
      extensive genotyping.

PMID- 25963004
TI  - Biomarkers of Alzheimer disease, insulin resistance, and obesity in childhood.
AB  - OBJECTIVE: To answer the question of whether onset of insulin resistance (IR)
      early in life enhances the risk of developing dementia and Alzheimer disease
      (AD), serum levels of 2 molecules that are likely associated with development of
      AD, the amyloid beta-protein 42 (Abeta42) and presenilin 1 (PSEN1), were
      estimated in 101 preschoolers and 309 adolescents of various BMI. METHODS:
      Participants (215 boys; 48.8%) were normal weight (n = 176; 40%), overweight (n =
      135; 30.7%), and obese (n = 129; 29.3%). The HOmeostasis Model of IR (HOMA-IR),
      HOMA percent beta-cell function (HOMA-beta) and QUantitative Insulin-sensitivity
      Check Index (QUICKI) were calculated. RESULTS: Obese adolescents had values of
      Abeta42 higher than overweight and normal-weight peers (190.2 +/- 9.16 vs 125.9
      +/- 7.38 vs 129.5 +/- 7.65 pg/mL; P < .0001) as well as higher levels of PSEN1
      (2.34 +/- 0.20 vs 1.95 +/- 0.20 vs 1.65 +/- 0.26 ng/mL; P < .0001).
      Concentrations of Abeta42 were significantly correlated with BMI (rho = 0.262; P
      < .0001), HOMA-IR (rho = 0.261; P < .0001) and QUICKI (rho = -0.220; P < .0001).
      PSEN1 levels were correlated with BMI (rho = 0.248; P < .0001), HOMA-IR (rho =
      0.242; P < .0001), and QUICKI (rho = -0.256; P < .0001). Western blot analysis
      confirmed that PSEN1 assays measured the full-length protein. CONCLUSION: Obese
      adolescents with IR present higher levels of circulating molecules that might be
      associated with increased risk of developing later in elderly cognitive
      impairment, dementia, and AD.

PMID- 25963005
TI  - Factors associated with meaningful use incentives in children's hospitals.
AB  - BACKGROUND AND OBJECTIVE: Among children's hospitals, little is known about how
      barriers to electronic health record (EHR) adoption are related to meaningful use
      (MU) incentives. We investigated hospital success with MU incentive payments and
      determined associations with hospital-reported challenges and characteristics.
      METHODS: A survey administered to 224 Children's Hospital Association hospitals
      assessed a variety of potential challenges to achieving meaningful EHR use (eg,
      lack of access to capital) and specific MU criteria that would be challenging to
      fulfill (eg, implement clinical decision support rules). These results were
      combined with data on hospitals that received MU payments up to March 2014 and
      information on hospital characteristics. Associations between anticipated
      challenges, children's hospital type, and receipt of MU incentives were evaluated
      in bivariate and multivariate analyses. RESULTS: One hundred thirty-three
      children hospitals completed the survey (response rate 59.4%). Thirty-five
      percent of responding children's hospitals received MU incentive payments. The
      most frequently anticipated hospital challenges included the following: exchange
      clinical information with other providers outside your hospital system (49%), and
      generate numerator and denominator data for quality reporting directly from EHR
      (41%). Freestanding children's hospitals were more likely to indicate lack of
      relevance of MU criteria to pediatric care (odds ratio: 37.6 [95% confidence
      interval: 4.6-309.3]) and more likely to receive MU incentive payments (odds
      ratio: 26 [95% confidence interval: 5.2-130.6]). CONCLUSIONS: As of 2014, a
      minority of children's hospitals have successfully received MU incentive
      payments. Freestanding children's hospitals are more likely to report MU is not
      relevant to pediatric care and to succeed with MU incentive payments.

PMID- 25963006
TI  - SIGIRR genetic variants in premature infants with necrotizing enterocolitis.
AB  - Necrotizing enterocolitis (NEC) is a severe form of bowel disease that develops
      in premature infants. Although animal data and human studies suggest that
      aberrant activation of the intestinal immune system contributes to NEC, the
      pathogenesis remains unclear. We hypothesized that inherited defects in the
      regulation of Toll-like receptor signaling can contribute to NEC susceptibility
      in premature infants. A forward genetic screen done in an infant with lethal NEC
      using exome sequencing identified a novel stop mutation (p.Y168X) and a rare
      missense variant (p.S80Y) in SIGIRR, a gene that inhibits intestinal Toll-like
      receptor signaling. Functional studies carried out in human embryonic kidney
      cells and intestinal epithelial cells demonstrated that SIGIRR inhibited
      inflammation induced by lipopolysaccharide, a cell wall component of Gram
      negative bacteria implicated in NEC. The genetic variants identified in the
      infant with NEC resulted in loss of SIGIRR function and exaggerated inflammation
      in response to lipopolysaccharide. Additionally, Sanger sequencing identified
      missense, stop, or splice region SIGIRR variants in 10 of 17 premature infants
      with stage II+ NEC. To the best of our knowledge, this is one of the first
      reports of a phenotype associated with SIGIRR in humans. Our data provide novel
      mechanistic insight into the probable causation of NEC and support additional
      investigation of the hypothesis that inherited defects in the regulation of
      innate immune signaling can contribute to NEC susceptibility in premature
      infants. 

PMID- 25963008
TI  - Outcomes of infants with indeterminate diagnosis detected by cystic fibrosis
      newborn screening.
AB  - BACKGROUND AND OBJECTIVES: Cystic fibrosis transmembrane conductance regulator
      related metabolic syndrome (CRMS) describes asymptomatic infants with a positive
      cystic fibrosis (CF) newborn screen (NBS) but inconclusive diagnostic testing for
      CF. Little is known about the epidemiology and outcomes of CRMS. The goal of this
      study was to determine the prevalence, clinical features, and short-term outcomes
      of infants with CRMS. METHODS: We analyzed data from the US CF Foundation Patient
      Registry (CFFPR) from 2010 to 2012. We compared demographic, diagnostic,
      anthropometric, health care utilization, microbiology, and treatment
      characteristics between infants with CF and infants with CRMS. RESULTS: There
      were 1983 infants diagnosed via NBS between 2010 and 2012 reported to the CFFPR.
      By using the CF Foundation guideline definitions, 1540 and 309 infants met the
      criteria for CF and CRMS, respectively (CF:CRMS ratio = 5.0:1.0). Of note, 40.8%
      of infants with CRMS were entered into the registry with a clinical diagnosis of
      CF. Infants with CRMS tended to have normal nutritional indices. However, 11% of
      infants with CRMS had a positive Pseudomonas aeruginosa respiratory tract culture
      in the first year of life. CONCLUSIONS: CRMS is a common outcome of CF NBS, and
      some infants with CRMS may develop features concerning for CF disease. A
      substantial proportion of infants with CRMS were assigned a clinical diagnosis of
      CF, which may reflect misclassification or clinical features not collected in the
      CFFPR.

PMID- 25963009
TI  - BMI and magnitude of scoliosis at presentation to a specialty clinic.
AB  - OBJECTIVE: To determine whether curve magnitude of scoliosis at presentation
      correlates with BMI. METHODS: Retrospective chart review of 180 patients
      presenting with scoliosis was performed. Curve pattern and magnitude, Risser
      status, occurrence of surgery, zip code, height and weight, race, and insurance
      status were recorded. Relationships were examined by Spearman rank and Pearson
      correlations, and logistic regression analysis was used to determine odds ratios.
      RESULTS: For both thoracic and lumbar curve patterns, there was a correlation
      between BMI and curve magnitude. Spearman rank correlation was 0.19 for thoracic
      (P = .03) and 0.24 for lumbar curves (P = .02). Overweight or obese patients were
      not more likely, however, to present with curves at higher risk of progression or
      more likely to have surgical intervention. With respect to potential confounding
      socioeconomic variables, thoracic curve magnitude was negatively correlated with
      median family income (Spearman rank correlation -0.17, P = .04). Curve magnitude
      was not correlated with race, distance, or insurance payer. CONCLUSIONS: Patients
      with high BMI and scoliosis are more likely to present with larger curves, but
      not more likely to require surgery. This is concerning because of the national
      trend of increasing childhood obesity and because scoliosis treatment may be more
      complicated in larger curves. Socioeconomic factors may also be barriers to
      access.

PMID- 25963010
TI  - Tdap in every pregnancy: circling the wagons around the newborn.

PMID- 25963011
TI  - Estimated number of infants detected and missed by critical congenital heart
      defect screening.
AB  - BACKGROUND AND OBJECTIVES: In 2011, the US Secretary of Health and Human Services
      recommended universal screening of newborns for critical congenital heart defects
      (CCHDs), yet few estimates of the number of infants with CCHDs likely to be
      detected through universal screening exist. Our objective was to estimate the
      number of infants with nonsyndromic CCHDs in the United States likely to be
      detected (true positives) and missed (false negatives) through universal newborn
      CCHD screening. METHODS: We developed a simulation model based on estimates of
      birth prevalence, prenatal diagnosis, late detection, and sensitivity of newborn
      CCHD screening through pulse oximetry to estimate the number of true-positive and
      false-negative nonsyndromic cases of the 7 primary and 5 secondary CCHD screening
      targets identified through screening. RESULTS: We estimated that 875 (95%
      uncertainty interval [UI]: 705-1060) US infants with nonsyndromic CCHDs,
      including 470 (95% UI: 360-585) infants with primary CCHD screening targets, will
      be detected annually through newborn CCHD screening. An additional 880 (UI: 700
      1080) false-negative screenings, including 280 (95% UI: 195-385) among primary
      screening targets, are expected. We estimated that similar numbers of CCHDs would
      be detected under scenarios comparing "lower" (~19%) and "higher" (~41%) than
      current prenatal detection prevalences. CONCLUSIONS: A substantial number of
      nonsyndromic CCHD cases are likely to be detected through universal CCHD
      screening; however, an equal number of false-negative screenings, primarily among
      secondary targets of screening, are likely to occur. Future efforts should
      document the true impact of CCHD screening in practice.

PMID- 25963012
TI  - Care coordination over time in medical homes for children with special health
      care needs.
AB  - OBJECTIVES: To explore how care coordination changes conceptually and practically
      in primary care practices when implementing the medical home and to identify
      reasons for different types of changes. METHODS: Six years after a 2003-2004
      national learning collaborative to implement the medical home model for children
      with special health care needs, we examined care coordination in 12 pediatric
      practices with the highest postintervention Medical Home Index scores, indicating
      high level of adoption of the model. Data included interviews of 48 clinicians,
      care coordinators, and parents and medical record reviews of 60 patients with
      special health care needs receiving care in these practices. RESULTS: Initially,
      care coordination activities were prompted by patients' acute problems, and over
      time activities, tools, and policies were implemented to avert many such problems
      and expand the scope of services offered to patients. Example activities were
      making previsit calls with families, writing care plans, developing relationships
      with community agencies, and tracking referrals. Although some activities were
      common across practices, the persons involved and efforts toward different
      activities varied with practice context. Drivers included motivation and
      creativity of medical home teams, organizational changes, funding to expand care
      coordinator positions, protected time for such activities, and adoption of
      electronic record systems. CONCLUSIONS: In high-performing medical homes, care
      coordination activities changed from being mostly reactive to patients' episodic
      needs to being more systematically proactive and comprehensive. This shift was
      promoted by factors external and internal to the practice. Ensuring these factors
      in medical home implementation may accelerate adoption of proactive care
      coordination activities.

PMID- 25963013
TI  - Clinical challenges in parental expression of hope and miracles.

PMID- 25963014
TI  - Academic effects of concussion in children and adolescents.
AB  - OBJECTIVE: The aim of this work is to study the nature and extent of the adverse
      academic effects faced by students recovering from concussion. METHOD: A sample
      of 349 students ages 5 to 18 who sustained a concussion and their parents
      reported academic concerns and problems (eg, symptoms interfering, diminished
      academic skills) on a structured school questionnaire within 4 weeks of injury.
      Postconcussion symptoms were measured as a marker of injury severity. Results
      were examined based on recovery status (recovered or actively symptomatic) and
      level of schooling (elementary, middle, and high school). RESULTS: Actively
      symptomatic students and their parents reported higher levels of concern for the
      impact of concussion on school performance (P < .05) and more school-related
      problems (P < .001) than recovered peers and their parents. High school students
      who had not yet recovered reported significantly more adverse academic effects
      than their younger counterparts (P < .05). Greater severity of postconcussion
      symptoms was associated with more school-related problems and worse academic
      effects, regardless of time since injury (P < .001). CONCLUSIONS: This study
      provides initial evidence for a concussion's impact on academic learning and
      performance, with more adverse effects reported by students who had not yet
      recovered from the injury. School-based management with targeted recommendations
      informed by postinjury symptoms may mitigate adverse academic effects, reduce
      parent and student concerns for the impact of the injury on learning and
      scholastic performance, and lower the risk of prolonged recovery for students
      with active postconcussion symptoms.

PMID- 25963007
TI  - Developmental outcomes of extremely preterm infants born to adolescent mothers.
AB  - BACKGROUND AND OBJECTIVES: Extremely preterm infants and infants born to
      adolescent mothers are at risk for adverse developmental. The objectives were to
      evaluate development and behavior outcomes of extremely low birth weight (ELBW)
      infants born to adolescent mothers <20 compared with adult mothers >=20 years and
      to identify socioeconomic risk factors that affect outcomes. METHODS:
      Retrospective cohort analysis of 211 infants >27 weeks of adolescent mothers and
      1723 infants of adult mothers at Neonatal Research Network centers from 2008 to
      2011. Groups were compared and regression models were run to predict 18- to 22
      month adverse outcomes. Primary outcomes were Bayley-III scores,
      neurodevelopmental impairment, and Brief Infant Toddler Social Emotional
      Assessment problem scores (BITSEA/P) >=75th percentile. RESULTS: Adolescent
      mothers were more often single, Hispanic, less educated, and had public
      insurance. By 18 to 22 months, their children had significantly increased rates
      of having lived >=3 places (21% vs 9%), state supervision (7% vs 3%),
      rehospitalization (56% vs 46%), and BITSEA/P >=75th percentile (50% vs 32%) and
      nonsignificant Bayley-III language scores <85 (56% vs 49%, P = .07). In
      regression analysis, children of adolescent mothers were more likely to have
      BITSEA/P >=75th percentile (relative risk 1.50, 95% confidence interval 1.08
      2.07). Living >=3 places and nonwhite race were predictors of adverse behavior.
      State supervision was an independent predictor of each Bayley-III composite <70
      and neurodevelopmental impairment. CONCLUSIONS: ELBW infants of adolescent
      mothers experience high social and environmental risks that are associated with
      adverse behavior outcomes. These findings inform the need for comprehensive
      follow-up, coordinated care services, and behavior interventions for ELBW infants
      of adolescent mothers.

PMID- 25963015
TI  - Persistent cat scratch disease requiring surgical excision in a patient with
      MPGN.
AB  - We present the case of a 13-year-old immunosuppressed patient with unrelenting
      cat scratch disease despite 9 months of antibiotic therapy. The patient was being
      treated with mycophenolate and prednisone for membranoproliferative
      glomerulonephritis (type 1) diagnosed 13 months before the onset of cat scratch
      disease. Cat scratch disease was suspected due to epitrochlear lymphadenitis and
      an inoculation papule on the ipsilateral thumb, and the diagnosis was confirmed
      by the use of acute and convalescent titers positive for Bartonella henselae. The
      patient experienced prolonged lymphadenitis despite azithromycin and rifampin
      therapy, and she developed a draining sinus tract ~4 months after initial
      inoculation while receiving antibiotics. Acute exacerbation of the primary
      supratrochlear node prompted incision and drainage of the area, with no
      improvement in the disease course. Ultimately, excision of all affected nodes and
      the sinus tract 9 months after the initial diagnosis was required to achieve
      resolution. Bartonella was detected at a high level according to a polymerase
      chain reaction assay in the excised nodes. Persistent treatment with oral
      antibiotics may have prevented disseminated infection in this immunosuppressed
      patient. Surgical excision of affected nodes should be considered in patients
      with cat scratch disease that persists beyond 16 weeks.

PMID- 25963016
TI  - High prevalence of CDH23 mutations in patients with congenital high-frequency
      sporadic or recessively inherited hearing loss.
AB  - BACKGROUND: Mutations in CDH23 are responsible for Usher syndrome 1D and
      recessive non-syndromic hearing loss. In this study, we revealed the prevalence
      of CDH23 mutations among patients with specific clinical characteristics.
      METHODS: After excluding patients with GJB2 mutations and mitochondrial m.1555A >
      G and m.3243A > G mutations, subjects for CDH23 mutation analysis were selected
      according to the following criteria: 1) Sporadic or recessively inherited hearing
      loss 2) bilateral non-syndromic congenital hearing loss, 3) no cochlear
      malformation, 4) a poorer hearing level at high frequencies than at low
      frequencies, and 5) severe or profound hearing loss at higher frequencies.
      RESULTS: Seventy-two subjects were selected from 621 consecutive probands who did
      not have environmental causes for their hearing loss. After direct sequencing, 13
      of the 72 probands (18.1%) had homozygous or compound heterozygous CDH23
      mutations. In total, we identified 16 CDH23 mutations, including five novel
      mutations. The 16 mutations included 12 missense, two frameshift, and two splice
      site mutations. CONCLUSIONS: These results revealed that CDH23 mutations are
      highly prevalent in patients with congenital high-frequency sporadic or
      recessively inherited hearing loss and that the mutation spectrum was diverse,
      indicating that patients with these clinical features merit genetic analysis.

PMID- 25963017
TI  - Intracranial amelanotic melanoma: a case report with literature review.
AB  - BACKGROUND: The incidence of primary central nervous system (CNS) melanocytic
      neoplasms is relatively low comparing to systemic ones. The performance of the
      tumor is variable. With poor clinical experience, the diagnosis and treatment of
      such tumors present to be a challenge. Amelanotic melanoma is an especially rare
      subtype. Only several cases have been reported. CASE PRESENTATION: We report a
      case of intracranial amelanotic melanoma. Preoperative assessment revealed
      progressive right frontal mass. The patient underwent tumor resection. The
      pathologic analysis reported amelanotic melanoma of intermediate grade. The
      further examination of the whole brain and body was negative. The familial
      history was also negative. The patient recovered uneventfully and went on for
      radiotherapy and chemotherapy. After a follow-up period of 5 months, the patient
      was tumor-free. CONCLUSIONS: This is the second report about primary CNS
      amelanotic melanoma. We summarized characteristics of the primary CNS melanocytic
      lesions and amelanotic melanoma with review of the literature and review of cases
      of our department.

PMID- 25963018
TI  - Do we need randomised trials for rare cancers?

PMID- 25963020
TI  - In regard to Livi et al. "Accelerated partial breast irradiation using intensity
      modulated radiotherapy versus whole breast irradiation: 5 year survival analysis
      of a phase 3 randomised controlled trial".

PMID- 25963021
TI  - Experience of burden in carers of people with dementia on the margins of long
      term care.
AB  - OBJECTIVES: This study aimed to identify the factors determining carer burden in
      a group of carers supporting people with dementia (PwD) deemed to be at high risk
      of moving to long-term residential or nursing home care. DESIGN: National data
      collected as part of the European RightTimePlaceCare project were analysed. This
      included 81 dyads of community-dwelling people with dementia and their informal
      carers. METHODS: Structured face-to-face interviews were conducted in North West
      England between June 2011 and April 2012. Interviews collected data relating to
      the person with dementia (cognitive functioning, activities of daily living,
      neuropsychiatric symptoms and formal and informal dementia care resource use) and
      carers' level of burden (22-item Zarit Burden Index), hours spent caring and
      availability of additional informal support. RESULTS: Logistic regression
      analysis identified five factors associated with high carer burden:
      neuropsychiatric symptomatology in the PwD, intensive supervision of the PwD by
      the carer, being a female carer, being an adult-child carer and absence of
      informal carer support. Use of home care or day care services was unrelated to
      burden. CONCLUSION: Support programmes focusing on challenging behaviours and
      risk management may be of benefit to carers. More individually tailored
      interventions for specific carer groups including female or younger carers may be
      warranted. The implementation of peer support networks could be beneficial to
      carers who lack additional family support.

PMID- 25963019
TI  - First-line single-agent panitumumab in frail elderly patients with wild-type KRAS
      metastatic colorectal cancer and poor prognostic factors: A phase II study of the
      Spanish Cooperative Group for the Treatment of Digestive Tumours.
AB  - BACKGROUND: Frail elderly patients with metastatic colorectal cancer (mCRC) are
      not candidates for chemotherapy. Monotherapy with anti-epidermal growth factor
      receptor (EGFR) monoclonal antibodies may be an option for these patients with
      few systemic toxic effects. PATIENTS AND METHODS: Single-arm, multicentre, phase
      II trial including patients ? 70y ears with wild-type (WT) KRAS (exon 2) mCRC,
      Eastern Cooperative Oncology Group (ECOG) status ? 3, KPC (Kohne Prognostic
      Classification)--defined intermediate or high risk status, frailty and/or
      ineligibility for chemotherapy. Patients received panitumumab until progression
      or unacceptable toxicity. The primary end-point was progression free survival
      (PFS) rate at 6 months. RESULTS: The study included 33 patients (intention-to
      treat (ITT) population). Median age: 81 years; sex: 66.7% male; high-risk KPC
      status: 45.4%. Median treatment duration was 14 weeks and 6-month PFS rate was
      36.4% (95% confidence interval (CI): 20.0-52.8). The objective response rate:
      9.1% (95% CI: 0-18.9) (all partial responses), and there were 18 stable diseases
      (54.5%). Median PFS was 4.3 months (95% CI: 2.8-6.4) and median overall survival
      (OS) was 7.1 months (95% CI: 5.0-12.3). There were no deaths or grade 4-5 adverse
      events (AEs) related to panitumumab and the most common grade 3-related AE was
      rash acneiform (15.2%). A significant association between clinical response and
      RAS status was observed (P=0.037). In the WT RAS subgroup (WT exons 2, 3, and 4
      of KRAS and NRAS, N = 15), 6-month PFS rate was 53.3% (95% CI: 30.1-75.2) and
      median PFS and OS were 7.9 and 12.3 months, respectively. CONCLUSIONS: Single
      agent panitumumab is active and well tolerated and may be a therapeutic option
      for high-risk frail elderly patients with WT RAS tumours considered not
      candidates for chemotherapy (clinicaltrials.gov identifier NCT01126112).

PMID- 25963022
TI  - Osteocalcin carboxylation is not associated with body weight or percent fat
      changes during weight loss in post-menopausal women.
AB  - Osteocalcin (OC) is a vitamin K-dependent bone protein used as a marker of bone
      formation. Mouse models have demonstrated a role for the uncarboxylated form of
      OC (ucOC) in energy metabolism, including energy expenditure and adiposity, but
      human data are equivocal. The purpose of this study was to determine the
      associations between changes in measures of OC and changes in body weight and
      percent body fat in obese, but otherwise healthy post-menopausal women undergoing
      a 20-week weight loss program. All participants received supplemental vitamins K
      and D and calcium. Body weight and body fat percentage (%BF) were assessed before
      and after the intervention. Serum OC [(total (tOC), ucOC, percent uncarboxylated
      (%ucOC)], and procollagen type 1N-terminal propeptide (P1NP; a measure of bone
      formation) were measured. Women lost an average of 10.9 +/- 3.9 kg and 4 %BF.
      Serum concentrations of tOC, ucOC, %ucOC, and P1NP did not significantly change
      over the twenty-week intervention, nor were these measures associated with
      changes in weight (all p > 0.27) or %BF (all p > 0.54). Our data do not support
      an association between any serum measure of OC and weight or %BF loss in post
      menopausal women supplemented with nutrients implicated in bone health.

PMID- 25963024
TI  - Biomolecular recognition of antagonists by alpha7 nicotinic acetylcholine
      receptor: Antagonistic mechanism and structure-activity relationships studies.
AB  - As the key constituent of ligand-gated ion channels in the central nervous
      system, nicotinic acetylcholine receptors (nAChRs) and neurodegenerative diseases
      are strongly coupled in the human species. In recently years the developments of
      selective agonists by using nAChRs as the drug target have made a large progress,
      but the studies of selective antagonists are severely lacked. Currently these
      antagonists rest mainly on the extraction of partly natural products from some
      animals and plants; however, the production of these crude substances is quite
      restricted, and artificial synthesis of nAChR antagonists is still one of the
      completely new research fields. In the context of this manuscript, our primary
      objective was to comprehensively analyze the recognition patterns and the
      critical interaction descriptors between target alpha7 nAChR and a series of the
      novel compounds with potentially antagonistic activity by means of virtual
      screening, molecular docking and molecular dynamics simulation, and meanwhile
      these recognition reactions were also compared with the biointeraction of alpha7
      nAChR with a commercially natural antagonist - methyllycaconitine. The results
      suggested clearly that there are relatively obvious differences of molecular
      structures between synthetic antagonists and methyllycaconitine, while the two
      systems have similar recognition modes on the whole. The interaction energy and
      the crucially noncovalent forces of the alpha7 nAChR-antagonists are ascertained
      according to the method of Molecular Mechanics/Generalized Born Surface Area.
      Several amino acid residues, such as B/Tyr-93, B/Lys-143, B/Trp-147, B/Tyr-188,
      B/Tyr-195, A/Trp-55 and A/Leu-118 played a major role in the alpha7 nAChR
      antagonist recognition processes, in particular, residues B/Tyr-93, B/Trp-147 and
      B/Tyr-188 are the most important. These outcomes tally satisfactorily with the
      discussions of amino acid mutations. Based on the explorations of three
      dimensional quantitative structure-activity relationships, the structure
      antagonistic activity relationships of antagonists and the characteristics of
      alpha7 nAChR-ligand recognitions were received a reasonable summary as well.
      These attempts emerged herein would not only provide helpful guidance for the
      design of alpha7 nAChR antagonists, but shed new light on the subsequent
      researches in antagonistic mechanism. 

PMID- 25963023
TI  - Evaluation of hearing functions in patients with euthyroid Hashimoto's
      thyroiditis.
AB  - Sensorineural hearing loss has been reported in various autoimmune diseases. The
      relationship between Hashimoto's thyroiditis (HT) and the auditory system has not
      been previously evaluated. In this study, we investigated the effect of euthyroid
      HT on the hearing ability of adult patients. The study included 30 patients with
      newly diagnosed euthyroid HT and 30 age- and gender-matched healthy controls. All
      subjects had a normal otoscopic examination and tympanometry, and they were
      negative for rheumatoid factor, antinuclear, anti-smooth muscle,
      antimitochondrial, antineutrophilcytoplasmic, and antigliadin antibodies. Pure
      tone audiometry exams at 250, 500, 1000, 2000, 4000, 6000, and 8000 Hertz (Hz)
      were performed in both groups. Thyroid peroxidase antibody and thyroglobulin
      antibody (anti-Tg) levels were higher in HT group while TSH, free T4, free T3,
      plasma electrolytes, glucose, lipid profile, vitamin B12, and blood pressure
      measurements were similar between the two groups. Higher audiometric thresholds
      and a higher prevalence of hearing loss at 250, 500, and 6000 Hz were detected in
      the HT patients than in the healthy controls (P < 0.05). Hearing levels at 250
      and 500 Hz correlated positively with anti-Tg levels (rho = 0.650, P = 0.002; rho
      = 0.719, P < 0.001, respectively), and this association remained significant in
      linear regression analysis. Anti-Tg-positive HT patients had higher hearing
      thresholds at 250 and 500 Hz than anti-Tg-negative HT patients. Hearing
      thresholds were similar between anti-Tg-negative HT patients and the control
      subjects. This study demonstrated that hearing functions are impaired in HT
      patients. Thyroid autoimmunity seems to have an important impact on a decreased
      hearing ability, particularly at lower frequencies, in this population of
      patients.

PMID- 25963025
TI  - Antimicrobial susceptibility of travel-related Salmonella enterica serovar Typhi
      isolates detected in Switzerland (2002-2013) and molecular characterization of
      quinolone resistant isolates.
AB  - BACKGROUND: Typhoid fever is an acute, invasive, and potentially fatal systemic
      infection caused by Salmonella enterica subspecies enterica serotype Typhi (S.
      Typhi). Drug resistance to antimicrobials such as ciprofloxacin is emerging in
      developing countries, threatening the efficacy of treatment of patients in
      endemic regions as well as of travellers returning from these countries. METHODS:
      We compared the antimicrobial resistance profiles of 192 S. Typhi isolated from
      patients over a time span of twelve years. Susceptibility testing was done by the
      disk diffusion method. A representative selection of isolates (n = 41) was
      screened by PCR for mutations in the quinolone resistance-determining regions
      (QRDRs) of the gyrA and parC genes and all 192 isolates were screened for plasmid
      mediated quinolone resistance (PMQR) genes. Multilocus sequence typing (MLST) was
      used to investigate the sequence type of isolates from patients with a known
      history of international travel. RESULTS: Resistance rates for nalidixic acid
      increased from 20 % to 66.7 % between 2002 and 2013. Resistance to ciprofloxacin
      was detected in 55.6 % of the isolates by 2013. Ciprofloxacin resistance was
      predominantly associated with the triple substitutions Ser83 -> Phe and Asp87 ->
      Asn in GyrA and Ser80 -> Ile in ParC. The plasmid-mediated resistance gene qnrS1
      was detected in two isolates. Sequence type ST1 was associated with the Indian
      subcontinent, while ST2 was distributed internationally. Multidrug resistance was
      noted for 11.5 % of the isolates. CONCLUSIONS: Fluoroquinolone resistant S. Typhi
      constitute a serious public health concern in endemic areas as well as in
      industrialized countries. Increased surveillance of global patterns of
      antimicrobial resistance is necessary and the control of resistant strains is of
      the utmost importance to maintain treatment options.

PMID- 25963027
TI  - Genome-wide association studies in biliary atresia.
AB  - Biliary atresia (BA) is a model complex disease resulting from interactions
      between multiple susceptibility loci and environmental factors. This perception
      is based on a heterogeneous phenotype extending beyond an absent extrahepatic
      bile duct to include gut and cardiovascular anomalies, and the association of BA
      with viral infections. Refractory jaundice and progression to cirrhosis shortly
      after birth can be fatal without surgical correction, and further suggests a
      pathogenesis during liver and bile duct development. Conclusive proof for a
      developmental origin would require documentation of disease progression in the
      perinatal or fetal liver, an impossible task for obvious reasons. We review three
      different sets of genome-wide association studies (GWAS) from three different
      cohorts of BA patients by three different groups of investigators, which address
      this knowledge gap. Knockdown of each susceptibility gene identified by GWAS in
      zebrafish embryos impairs excretion of bile from the liver, duplicating the
      characteristic diagnostic finding seen in affected children. This finding is
      associated with impaired intrahepatic biliary network formation in zebrafish
      morphants. Although distinct, these susceptibility genes share several functions
      including roles in mechanisms for organogenesis (glypican 1 or GPC1, and
      adenosine diphosphate ribosylation factor 6, or ARF6) or a greater expression in
      fetal liver than in adult liver (adducin 3 or ADD3). Together, these studies
      emphasize the importance of the human evidence, and present opportunities to map
      novel pathways which explain the phenotypic heterogeneity of BA.

PMID- 25963026
TI  - Neutrophil extracellular traps can activate alternative complement pathways.
AB  - The interaction between neutrophils and activation of alternative complement
      pathway plays a pivotal role in the pathogenesis of anti-neutrophil cytoplasmic
      antibody (ANCA)-associated vasculitis (AAV). ANCAs activate primed neutrophils to
      release neutrophil extracellular traps (NETs), which have recently gathered
      increasing attention in the development of AAV. The relationship between NETs and
      alternative complement pathway has not been elucidated. The current study aimed
      to investigate the relationship between NETs and alternative complement pathway.
      Detection of components of alternative complement pathway on NETs in vitro was
      assessed by immunostain and confocal microscopy. Complement deposition on NETs
      were detected after incubation with magnesium salt ethyleneglycol tetraacetic
      acid (Mg-EGTA)-treated human serum. After incubation of serum with supernatants
      enriched in ANCA-induced NETs, levels of complement components in supernatants
      were measured by enzyme-linked immunosorbent assay (ELISA). Complement factor B
      (Bb) and properdin deposited on NETs in vitro. The deposition of C3b and C5b-9 on
      NETs incubated with heat-inactivated normal human serum (Hi-NHS) or EGTA-treated
      Hi-NHS (Mg-EGTA-Hi-NHS) were significantly less than that on NETs incubated with
      NHS or EGTA-treated NHS (Mg-EGTA-NHS). NETs induced by ANCA could activate the
      alternative complement cascade in the serum. In the presence of EGTA, C3a, C5a
      and SC5b-9 concentration decreased from 800.42 +/- 244.81 ng/ml, 7.68 +/- 1.50
      ng/ml, 382.15 +/- 159.75 ng/ml in the supernatants enriched in ANCA induced NETs
      to 479.07 +/- 156.2 ng/ml, 4.86 +/- 1.26 ng/ml, 212.65 +/- 44.40 ng/ml in the
      supernatants of DNase I-degraded NETs (P < 0.001, P = 0.008, P < 0.001,
      respectively). NETs could activate the alternative complement pathway, and might
      thus participate in the pathogenesis of AAV. 

PMID- 25963028
TI  - A combination of positive dielectrophoresis driven on-line enrichment and aptamer
      fluorescent silica nanoparticle label for rapid and sensitive detection of
      Staphylococcus aureus.
AB  - Staphylococcus aureus (S. aureus) is an important human pathogen that causes
      several diseases ranging from superficial skin infections to life-threatening
      diseases. Here, a method combining positive dielectrophoresis (pDEP) driven on
      line enrichment and aptamer-fluorescent silica nanoparticle label has been
      developed for the rapid and sensitive detection of S. aureus in microfluidic
      channels. An aptamer, having high affinity to S. aureus, is used as the molecular
      recognition tool and immobilized onto chloropropyl functionalized fluorescent
      silica nanoparticles through a click chemistry approach to obtain S. aureus
      aptamer-nanoparticle bioconjugates (Apt(S.aureus)/FNPs). The pDEP driven on-line
      enrichment technology was used for accumulating the Apt(S.aureus)/FNP labeled S.
      aureus. After incubating with S. aureus, the mixture of Apt(S.aureus)/FNP labeled
      S. aureus and Apt(S.aureus)/FNPs was directly introduced into the pDEP-based
      microfluidic system. By applying an AC voltage in a pDEP frequency region, the
      Apt(S.aureus)/FNP labelled S. aureus moved to the electrodes and accumulated in
      the electrode gap, while the free Apt(S.aureus)/FNPs flowed away. The signal that
      came from the Apt(S.aureus)/FNP labelled S. aureus in the focused detection areas
      was then detected. Profiting from the specificity of aptamer, signal
      amplification of FNP label and pDEP on-line enrichment, this assay can detect as
      low as 93 and 270 cfu mL(-1)S. aureus in deionized water and spiked water
      samples, respectively, with higher sensitivities than our previously reported
      Apt(S.aureus)/FNP based flow cytometry. Moreover, without the need for separation
      and washing steps usually required for FNP label involved bioassays, the total
      assay time including sample pretreatment was within 2 h.

PMID- 25963029
TI  - Cancer research in the era of next-generation sequencing and big data calls for
      intelligent modeling.
AB  - We examine the role of big data and machine learning in cancer research. We
      describe an example in cancer research where gene-level data from The Cancer
      Genome Atlas (TCGA) consortium is interpreted using a pathway-level model. As the
      complexity of computational models increases, their sample requirements grow
      exponentially. This growth stems from the fact that the number of combinations of
      variables grows exponentially as the number of variables increases. Thus, a large
      sample size is needed. The number of variables in a computational model can be
      reduced by incorporating biological knowledge. One particularly successful way of
      doing this is by using available gene regulatory, signaling, metabolic, or
      context-specific pathway information. We conclude that the incorporation of
      existing biological knowledge is essential for the progress in using big data for
      cancer research. 

PMID- 25963030
TI  - Transfusion of fresher versus older red blood cells for all conditions.
AB  - BACKGROUND: Red blood cell transfusion is a common treatment for anaemia in many
      clinical conditions. One current concern is uncertainty as to the clinical
      consequences (notably efficacy and safety) of transfusing red blood cell units
      that have been stored for different durations of time before a transfusion. If
      evidence from randomised controlled trials were to indicate that clinical
      outcomes are affected by storage age, the implications for inventory management
      and clinical practice would be significant. OBJECTIVES: To assess the effects of
      using fresher versus older red blood cells in people requiring a red blood cell
      transfusion. SEARCH METHODS: We ran the search on 29th September 2014. We
      searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE
      (OvidSP), Embase (OvidSP), CINAHL (EBSCO), PubMed (for e-publications), three
      other databases and trial registers. SELECTION CRITERIA: We included randomised
      controlled trials comparing fresher red blood cell transfusion versus active
      transfusion of older red blood cells, and comparing fresher red blood cell
      transfusion versus current standard practice. All definitions of 'fresher' and
      'older'/'standard practice' red blood cells were included. DATA COLLECTION AND
      ANALYSIS: Two review authors independently assessed trial quality and extracted
      from the trial report data on adverse red blood cell transfusion reactions, when
      reported. MAIN RESULTS: We included 16 trials (1864 participants) in the review.
      Eight trials (279 participants) compared transfusion of fresher red blood cells
      versus transfusion of older stored red blood cells ('fresher' vs 'older'). Eight
      trials (1585 participants) compared the transfusion of fresher red blood cells
      versus current standard practice ('fresher' vs 'standard practice'). Five trials
      enrolled neonates, one trial enrolled children and 12 trials enrolled adults.
      Overall sample sizes were small: only two trials randomly assigned more than 100
      participants.We performed no meta-analyses for a variety of reasons: no uniform
      definition of 'fresher' or 'older' red blood cell storage; overlap in the
      distribution of the age of red blood cells; and heterogeneity in measurements and
      reporting of outcomes of interest to this review. We tabulated and reported
      results by individual trial. Overall risk of bias was low or unclear, with four
      incidences of high risk of bias: in allocation concealment (three trials) and in
      incomplete outcome data (one trial).No trial measured all of the outcomes of
      interest in this review. Four trials comparing 'fresher' with 'older' red blood
      cells reported the primary outcome: mortality within seven days (one study; 74
      participants) and at 30 days (three trials; 62 participants). Six trials
      comparing 'fresher' with 'standard practice' red blood cells reported the primary
      outcome: mortality within seven days (three studies; 159 participants) and at 30
      days (three trials; 1018 participants). All 10 trials reported no clear
      differences in mortality at either time point between intervention arms.Three
      trials comparing 'fresher' with 'standard practice' red blood cells reported red
      blood cell transfusion-associated adverse events. No adverse reactions were
      reported in two trials, and one incidence of cytomegalovirus (CMV) infection was
      described in the 'standard practice' arm in one trial.Overall the trials reported
      no clear difference between either of the intervention comparisons in long-term
      mortality (three trials; 478 participants); clinically accepted measures of
      multiple organ dysfunction (two trials: 399 participants); incidence of in
      hospital infection (two trials; 429 participants); duration of mechanical
      ventilation (three trials: 95 participants); and number of participants requiring
      respiratory organ support (five trials; 528 participants) or renal support (one
      trial; 57 participants). The outcome 'physiological markers of oxygen consumption
      or alterations in microcirculation' was reported by 11 studies, but the measures
      used were highly varied, and no formal statistical analysis was undertaken.
      AUTHORS' CONCLUSIONS: Several factors precluded firm conclusions about the
      clinical outcomes of transfusing red blood cell units that have been stored for
      different periods of time before transfusion, including differences in clinical
      population and setting, diversity in the interventions used, methodological
      limitations and differences in how outcomes were measured and reported.No clear
      differences in the primary outcome - death - were noted between 'fresher' and
      'older' or 'standard practice' red blood cells in trials that reported this
      outcome. Findings of a large number of ongoing trials will be incorporated into
      this review when they are published.Updates of this review will explore the
      degree of overlap in trials between 'fresher', 'older' and 'standard practice'
      storage ages of red blood cells and will consider whether the size of any
      observed effects is dependent on recipient factors such as clinical background,
      patient age or clinical presentation.

PMID- 25963031
TI  - [Myocarditis in the differential diagnosis of cardiomyopathies. Endomyocardial
      biopsy or MRI?].
AB  - Myocarditis is an inflammatory disease of the heart muscle commonly caused by
      viral pathogens. Dilated cardiomyopathy is a major long-term sequela of
      myocarditis and at least in part related to post-viral immune-mediated responses.
      Establishing a diagnosis of myocarditis represents a major challenge because of
      the variable clinical picture and the lack of readily available, non-invasive
      diagnostic tests. In recent years, cardiac magnetic resonance imaging (cMRI) has
      emerged as a promising additional diagnostic tool in patients with suspected
      myocarditis: cMRI not only provides important insights into structural and
      functional abnormalities of the heart but relevant tissue pathologies can also be
      visualized. The diagnostic accuracy of three tissue criteria, i.e. the edema
      ratio, early gadolinium enhancement ratio and late gadolinium enhancement, has
      been characterized in several studies. Endomyocardial biopsy (EMB) is widely
      considered to be the reference standard for diagnosis of myocarditis. Although
      limited by sampling error, EMB is the only diagnostic procedure that can be used
      to confirm myocarditis. Laboratory analyses of EMB may provide information about
      specific causes of myocarditis and are, at least in part, of prognostic
      relevance. In a subset of patients the results of EMB may guide therapeutic
      decision-making. Additional efforts are needed in cardiac imaging, molecular
      characterization of EMB and evaluation of serum biomarkers to improve the
      diagnostic work-up in patients with suspected myocarditis and to identify
      potential novel targets for a cause-specific therapy of myocarditis. 

PMID- 25963032
TI  - [Hypertrophic and restrictive cardiomyopathy. Differentiation by imaging].
AB  - The differentiation between hypertrophic and restrictive cardiomyopathies is
      often challenging in the routine clinical setting. Advances in the field of
      multimodal imaging have improved the diagnostics of these diseases and
      understanding of the underlying pathophysiology. Each imaging method, such as
      echocardiography, cardiac magnetic resonance imaging (CMR), cardiac computed
      tomography (CT) and coronary angiography including cardiac catheterization for
      pressure measurements, is of significant value in clinical diagnostics and also
      regarding therapeutic approaches and prognostic implications. This review gives
      an overview of developments of the past few years, describes recent insights and
      puts these findings into a scientific context. Particularly CMR has added
      valuable information to current knowledge by its unique potential of contrast
      enhanced tissue characterization. Another promising CMR tool, parametric mapping
      has appeared on the horizon and may further deepen our understanding of cardiac
      pathophysiology as well as offer new therapeutic options to patients. 

PMID- 25963033
TI  - [Aortic valve stenosis: computed tomography prior to transcatheter aortic valve
      implantation (TAVI). How can the outcome be improved?].
AB  - Computed tomography (CT) plays an important role in the preinterventional work-up
      of patients referred for transcatheter aortic valve implantation (TAVI). Contrast
      enhanced CT allows a comprehensive examination with evaluation of both the
      vascular access route as well as aortic valve and aortic root geometry. Analysis
      of the minimum luminal vessel diameter, tortuosity and vascular calcification are
      important to determine the ability to perform the procedure via a transfemoral
      access. The size of the aortic annulus can be accurately measured by CT to aid
      selection of the appropriate prosthesis and the use of CT for prosthesis sizing
      has been associated with a decreased incidence of paravalvular leakage as
      compared to 2-dimensional echocardiography. In addition CT permits accurate
      assessment of aortic root anatomy, distance between coronary ostia and the
      annulus plane as well as the dimensions of the ascending aorta. Furthermore,
      suitable fluoroscopic projections that permit an exact orthogonal visualization
      of the aortic annulus plane by fluoroscopy during the procedure can be extracted
      from the CT data set. In summary, CT permits comprehensive imaging in TAVI
      candidates and optimizes procedural outcome. 

PMID- 25963034
TI  - [Noncompaction cardiomyopathy].
AB  - Noncompaction cardiomyopathy (NCCM) is a genetic myocardial disorder, which is
      characterized by a two-layered ventricle wall with a thin compact outer layer and
      a noncompacted inner layer, with prominent trabeculations and deep
      intratrabecular recesses communicating with the ventricle cavity without any
      contact to the coronary system. Before the initial description as isolated left
      ventricle cardiomyopathy (ILVCN) in 1984 by Engberding and Bender, the
      morphological characteristics had been described only in association with other
      congenital cardiac disorders, such as atresia of the semilunar valves. The
      disease usually involves the myocardium of the left ventricle but involvement of
      the right ventricular has recently been shown. Due to delayed diagnosis and
      therapy, in advanced stages NCCM can result in heart failure. Life-threatening
      complications, such as malignant arrhythmia with sudden cardiac death and embolic
      events have been observed in patients with NCCM. A multimodal investigation
      including echocardiography and cardiac magnet resonance tomography (CMR) as well
      as a focused analysis of symptoms can allow a valid diagnosis. 

PMID- 25963036
TI  - [Diagnostics in structural heart diseases].

PMID- 25963035
TI  - [Structure and function of the mitral valve. Eligibility criteria for surgical
      and interventional approaches].
AB  - Mitral valve disease, especially severe mitral valve insufficiency, is an
      increasing issue in our population. Older patients with multiple comorbidities in
      particular are often denied surgery due to an increased perioperative risk.
      Because conservative medical treatment of mitral valve disease is often
      unsatisfactory, interventional techniques to treat mitral valve disease have
      emerged in recent years as serious alternatives to surgical treatment. Innovative
      developments in cardiovascular imaging have opened up new ways of looking at the
      mitral valve for improved diagnostic and therapeutic management of patients with
      mitral valve disease. These advantages of imaging are important for correct
      patient selection with either surgical or interventional strategies. This review
      describes the diagnostic capabilities of echocardiographic techniques for a
      precise diagnosis of the mitral valve structure and function for planning and
      performing interventional or surgical procedures. 

PMID- 25963037
TI  - Accentuate the positive: Counteracting psychogenic responses to media health
      messages in the age of the Internet.
AB  - OBJECTIVE: The Internet has expanded the scope for creating health scares and
      increased the risk of nocebo responding in individuals exposed to misinformation
      about threats to personal health posed by aspects of modern life, such as
      exposure to new technologies. It was the aim of this experiment to investigate
      whether the delivery of positive expectations might reduce or reverse symptoms
      triggered by negative expectations formed from such misinformation. METHOD: In
      the context of a study investigating symptoms during exposure to windfarm sound,
      64 volunteers assessed their symptomatic experiences during two discrete
      sessions, throughout which they listened to wind turbine sound containing audible
      and sub-audible (infrasound) components. Participants were randomly assigned to
      watch either positive or negative information about the health effects of
      infrasound prior to their first infrasound exposure session. They were then shown
      the alternate information and exposed to infrasound during their second session.
      RESULTS: Participants receiving negative expectations were less symptomatic
      during exposure if they had previously received positive expectations about
      infrasound. Further, participants given positive expectations after the earlier
      delivery of negative expectations exhibited a placebo response, reversing the
      nocebo response exhibited in their first exposure session. CONCLUSION: Results
      suggest accessing positively framed health information may reverse or dilute the
      effect of negative expectations formed from exposure to media warnings about
      health risks posed by new technologies, such as wind turbines.

PMID- 25963038
TI  - Comparative Effectiveness of Medical Therapy, Supervised Exercise, and
      Revascularization for Patients With Intermittent Claudication: A Network Meta
      analysis.
AB  - BACKGROUND: There are limited data on the comparative effectiveness of medical
      therapy, supervised exercise, and revascularization to improve walking and
      quality of life in patients with intermittent claudication (IC). HYPOTHESIS:
      Supervised exercise and revascularization was superior to medical therapy in IC.
      METHODS: We studied the comparative effectiveness of exercise training,
      medications, endovascular intervention, and surgical revascularization on
      outcomes including functional capacity (walking distance and timing), quality of
      life, and mortality. We searched PubMed, EMBASE, and the Cochrane Database of
      Systematic Reviews from January 1995 to August 2012 for relevant English-language
      studies. Two investigators independently collected data. Meta-analyses with
      random-effects models of direct comparisons were supplemented by mixed-treatment
      analyses to incorporate data from placebo comparisons, head-to-head comparisons,
      and multiple treatment arms. RESULTS: Thirty-five unique studies evaluated
      treatment modalities in 7475 patients with IC. Compared with usual care, only
      exercise training improved both maximal walking distance (150 meters; 95%
      confidence interval: 35-266 meters, P = 0.01) and initial claudication distance
      (39 meters; 95% confidence interval: 9-65 meters, P = 0.003). All modalities were
      associated with improved quality of life (Short Form-36 physical functioning
      score) compared with usual care, but there were no differences between
      treatments. There were insufficient safety data to assess treatment-related
      complications. All-cause mortality was not significantly different between
      modalities. CONCLUSIONS: Evidence is insufficient to determine treatment
      superiority for improving quality of life and walking parameters in IC patients.
      Further studies with attention to study design, standardized efficacy and safety
      endpoints, and appropriate subgroup reporting are necessary to determine
      comparative effectiveness.

PMID- 25963039
TI  - Rhodium(III)-Catalyzed [4+1] Annulation of Aromatic and Vinylic Carboxylic Acids
      with Allenes: An Efficient Method Towards Vinyl-Substituted Phthalides and 2
      Furanones.
AB  - A highly regio- and stereoselective synthesis of 3,3-disubstituted phthalides
      from aryl carboxylic acids and allenes using a rhodium(III) catalyst has been
      demonstrated. The reaction features broad functional group tolerance and provides
      a simple and straightforward route to the synthesis of various 3-vinyl
      substituted phthalides. Furthermore, the catalytic reaction can also be applied
      to the synthesis of biologically active 5-vinyl-substituted 2-furanones from
      alpha,beta-unsaturated carboxylic acids and allenes. The reactions proceed
      through a carboxylate-assisted ortho-C?H activation and [4+1] annulation. The
      preliminary mechanistic studies suggest that a C?H cleavage is the rate
      determining step. 

PMID- 25963040
TI  - Temperature Affects Human Sweet Taste via At Least Two Mechanisms.
AB  - The reported effects of temperature on sweet taste in humans have generally been
      small and inconsistent. Here, we describe 3 experiments that follow up a recent
      finding that cooling from 37 to 21  degrees C does not reduce the initial
      sweetness of sucrose but increases sweet taste adaptation. In experiment 1,
      subjects rated the sweetness of sucrose, glucose, and fructose solutions at 5-41 
      degrees C by dipping the tongue tip into the solutions after 0-, 3-, or 10-s pre
      exposures to the same solutions or to H2O; experiment 2 compared the effects of
      temperature on the sweetness of 3 artificial sweeteners (sucralose, aspartame,
      and saccharin); and experiment 3 employed a flow-controlled gustometer to rule
      out the possibility the effects of temperature in the preceding experiments were
      unique to dipping the tongue into a still taste solution. The results (i)
      confirmed that mild cooling does not attenuate sweetness but can increase sweet
      taste adaptation; (ii) demonstrated that cooling to 5-12  degrees C can directly
      reduce sweetness intensity; and (iii) showed that both effects vary across
      stimuli. These findings have implications for the TRPM5 hypothesis of thermal
      effects on sweet taste and raise the possibility that temperature also affects an
      earlier step in the T1R2-T1R3 transduction cascade. 

PMID- 25963041
TI  - Variation of prostaglandin E2 concentrations in ovaries and its effects on
      ovarian maturation and oocyte proliferation in the giant fresh water prawn,
      Macrobrachium rosenbergii.
AB  - Prostaglandins (PGs) are important bioactive mediators for many physiological
      functions. In some decapod crustaceans, prostaglandin E2 (PGE2) has been detected
      in reproductive organs, and may play a role in the control of ovarian maturation.
      However, in the freshwater prawn, Macrobrachium rosenbergii, the presences of
      PGE2 and key enzymes for PGE2 biosynthesis, as well as its effects on ovarian
      maturation have not yet been investigated. In this study we reported the presence
      of PGE2, cyclooxygenase1 (COX1) and prostaglandin E synthase (PGES) in the
      ovarian tissues of M. rosenbergii, using immunohistochemistry. Intense
      immunoreactivities of PGE2 (PGE2-ir), COX1 (Cox1-ir) and PGES (PGES-ir) were
      detected in previtellogenic oocytes (Oc1 and Oc2), while the immunoreactivities
      were absent in the late vitellogenic oocytes (Oc4). This finding supports the
      hypothesis that the PGE2 biosynthesis occurs in the ovary of this prawn. To
      ascertain this finding we used LC-MS/MS to quantitate PGE2 concentrations during
      ovarian developmental cycle. The levels of PGE2 were significantly higher in the
      early ovarian stages (St I and II) than in the late stages (St III and IV).
      Moreover, we found that administration of PGE2 stimulated the ovarian maturation
      in this species by shortening the length of the ovarian cycle, increasing ovarian
      somatic index, oocyte proliferation, and vitellogenin (Vg) level in the
      hemolymph.

PMID- 25963042
TI  - The liver of goldfish as a component of the circadian system: Integrating a
      network of signals.
AB  - The circadian system drives daily physiological and behavioral rhythms that allow
      animals to anticipate cyclic environmental changes. The discovery of the known as
      "clock genes", which are very well conserved through vertebrate phylogeny,
      highlighted the molecular mechanism of circadian oscillators functioning, based
      on transcription and translation cycles (~ 24 h) of such clock genes. Studies in
      goldfish have shown that the circadian system in this species is formed by a net
      of oscillators distributed at central and peripheral locations, as the retina,
      brain, gut and liver, among others. In this work we review the existing
      information about the hepatic oscillator in goldfish due to its relevance in
      metabolism, and its key role as target of a variety of humoral signals. Different
      input signals modify the molecular clockwork in the liver of goldfish. Among
      them, there are environmental cues (photocycle and feeding regime) and different
      encephalic and peripheral endogenous signals (orexin, ghrelin and
      glucocorticoids). Per clock genes seem to be a common target for different
      signals. Thus, this genes family might be important for shifting the hepatic
      oscillator. The physiological relevance of the crosstalking between metabolic and
      feeding-related hormones and the hepatic clock sets the stage for the hypothesis
      that these hormones could act as "internal zeitgebers" communicating oscillators
      in the goldfish circadian system.

PMID- 25963043
TI  - Genomic and functional characterization of a methoprene-tolerant gene in the
      kissing-bug Rhodnius prolixus.
AB  - Metamorphosis, which depends upon a fine balance between two groups of lipid
      soluble hormones such as juvenile hormones (JHs) and ecdysteroids, is an
      important feature in insect evolution. While it is clear that the onset of
      metamorphosis depends on the decrease of JH levels, the way in which these
      hormones exert their activities is not fully understood in Triatominae species.
      The discovery of a Drosophila melanogaster mutant resistant to the treatment with
      the JH analog methoprene, led finally to the description of the methoprene
      tolerant gene in Tribolium castaneum (TcMet) as a putative JH receptor. Here we
      present the genomic and functional characterization of an ortholog of the
      methoprene-tolerant gene in the hemimetabolous insect Rhodnius prolixus (RpMet).
      The analysis of the R. prolixus gene showed that the exonic structure is
      different from that described for holometabolous species, although all the
      critical protein motifs are well conserved. Expression analysis showed the
      presence of RpMet mRNA in all the tested tissues: ovary, testis, rectum,
      Malpighian tubules and salivary glands. When juvenile individuals were treated
      with RpMet specific double strand RNA (dsRNA), we observed abnormal molting
      events that resulted in individuals with morphological alterations (adultoids).
      Similarly, treatment of newly emerged fed females with dsRNA resulted in an
      abnormal development of the ovaries, with eggs revealing anomalies in size and
      accumulation of yolk, as well as a decrease in the amount of heme-binding
      protein. Altogether, our results validate that RpMet is involved in the
      transduction of JH signaling, controlling metamorphosis and reproduction in R.
      prolixus. 

PMID- 25963044
TI  - Anorexigenic effect of serotonin is associated with changes in hypothalamic
      nuclei activity in an avian model.
AB  - The anorexigenic effect of serotonin (5HT) has been documented for decades;
      however, its central mechanism has not been fully elucidated, especially so in
      non-mammalian vertebrates. Therefore, we centrally injected 5HT to chicks and
      measured several appetite-associated parameters. Chicks that received central 5HT
      dose- and time-dependently decreased food intake while water intake was not
      affected. To determine which hypothalamic nuclei were associated with this effect
      c-Fos immunoreactivity was measured in appetite-associated nuclei. Only the
      ventromedial hypothalamus and arcuate nucleus were activated. Whole blood glucose
      was measured after 5HT injection but was not affected. From the hypothalamus,
      several appetite-associated mRNAs were measured by real-time PCR after 5HT
      injection but not one of these showed any difference in expression. Lastly, a
      comprehensive behavior analysis demonstrated that 5HT caused reducing pecking and
      increased deep rest. Together we interpret these results as exogenous 5HT
      injection causes short term satiety that is likely a secondary effect to an
      increase in the amount of time spent in deep rest.

PMID- 25963045
TI  - Philosophy of race meets population genetics.
AB  - In this paper, I respond to four common semantic and metaphysical objections that
      philosophers of race have launched at scholars who interpret recent human genetic
      clustering results in population genetics as evidence for biological racial
      realism. I call these objections 'the discreteness objection', 'the visibility
      objection', 'the very important objection', and 'the objectively real objection.'
      After motivating each objection, I show that each one stems from implausible
      philosophical assumptions about the relevant meaning of 'race' or the nature of
      biological racial realism. In order to be constructive, I end by offering some
      advice for how we can productively critique attempts to defend biological racial
      realism based on recent human genetic clustering results. I also offer a
      clarification of the relevant human-population genetic research. 

PMID- 25963046
TI  - A novel TBX5 loss-of-function mutation associated with sporadic dilated
      cardiomyopathy.
AB  - Dilated cardiomyopathy (DCM) represents the most prevalent form of primary
      cardiomyopathy, and is the most common reason for heart transplantation and a
      major cause of congestive heart failure. Aggregating evidence demonstrates that
      genetic defects are associated with DCM, and a great number of mutations in >50
      genes have been linked to DCM. However, DCM is a genetically heterogeneous
      disorder and the genetic components underpinning DCM in a significant proportion
      of patients remain unknown. In the present study, the coding exons and flanking
      exon-intron boundaries of the T-Box 5 (TBX5) gene, which encodes a T-box
      transcription factor required for normal cardiac development, were sequenced in
      146 unrelated patients with sporadic DCM. The functional characteristics of the
      mutant TBX5 were assayed in contrast to its wild-type counterpart by using a dual
      luciferase reporter assay system. As a result, a novel heterozygous TBX5
      mutation, p.A143T, was identified in a patient with sporadic DCM. The missense
      mutation, which was absent in 400 control chromosomes, altered the amino acid
      that was completely conserved evolutionarily among species. Biological analyses
      revealed that the A143T mutation of TBX5 was associated with significantly
      decreased transcriptional activity on the promoter of the target gene atrial
      natriuretic factor (ANF), when compared to its wild-type counterpart.
      Furthermore, the A143T mutation abolished the synergistic activation of the ANF
      promoter between TBX5 and GATA binding protein 4 (GATA4), another crucial
      transcriptional factor for heart development. To the best of our knowledge, this
      is the first report on the association of a TBX5 loss-of-function mutation with
      an enhanced susceptibility to sporadic DCM, providing novel insight into the
      molecular mechanisms of the pathogenesis of DCM and suggesting potential
      implications for the prenatal prophylaxis and personalized treatment of this
      commonest primary myocardial disease.

PMID- 25963047
TI  - Mixture regression models for closed population capture-recapture data.
AB  - In capture-recapture studies, the use of individual covariates has been
      recommended to get stable population estimates. However, some residual
      heterogeneity might still exist and ignoring such heterogeneity could lead to
      underestimating the population size (N). In this work, we explore two new models
      with capture probabilities depending on both covariates and unobserved random
      effects, to estimate the size of a population. Inference techniques including
      Horvitz-Thompson estimate and confidence intervals for the population size, are
      derived. The selection of a particular model is carried out using the Akaike
      information criterion (AIC). First, we extend the random effect model of Darroch
      et al. (1993, Journal of American Statistical Association 88, 1137-1148) to
      handle unit level covariates and discuss its limitations. The second approach is
      a generalization of the traditional zero-truncated binomial model that includes a
      random effect to account for an unobserved heterogeneity. This approach provides
      useful tools for inference about N, since key quantities such as moments,
      likelihood functions and estimates of N and their standard errors have closed
      form expressions. Several models for the unobserved heterogeneity are available
      and the marginal capture probability is expressed using the Logit and the
      complementary Log-Log link functions. The sensitivity of the inference to the
      specification of a model is also investigated through simulations. A numerical
      example is presented. We compare the performance of the proposed estimator with
      that obtained under model Mh of Huggins (1989 Biometrika 76, 130-140). 

PMID- 25963048
TI  - Evaluation of brief screens for gambling disorder in the substance use treatment
      setting.
AB  - BACKGROUND AND OBJECTIVES: The goal of this study was to determine the diagnostic
      accuracy of brief screens for Gambling Disorder within a sample of people
      receiving outpatient treatment for substance use disorders. METHODS: Individuals
      (n = 300) recruited from intensive outpatient substance use treatment (23.67%) or
      methadone maintenance programs (76.34%) participated in the study. Four brief
      screens for Gambling Disorder were administered and compared to DSM-5 criteria.
      Receiver operator curves were created and an Area Under the Curve (AUC) analysis
      (an overall summary of the utility of the scale to correctly identify Gambling
      Disorder) was assessed for each. RESULTS: On average participants were aged 46.4
      years (SD = 10.2), African American/Black (70.7%), with an income less than
      $20,000/year (89.5%). Half the participants were female. Approximately 40% of
      participants (40.5%; n = 121) met DSM-5 criteria for Gambling Disorder. Accuracy
      of the brief screens as measured by hit rate were .88 for the BBGS, .77 for the
      Lie/Bet, .75 for NODS-PERC, and .73 for the NODS-CLiP. AUC analysis revealed that
      the NODS-PERC (AUC: .93 (95% CI: .91-.96)) and NODS-CLiP (AUC: .90 (95% CI: .86
      .93)) had excellent accuracy. DISCUSSION AND CONCLUSIONS: The NODS-PERC and NODS
      CLiP had excellent accuracy at all cut-off points. However, the BBGS appeared to
      have the best accuracy at its specified cut-off point. SCIENTIFIC SIGNIFICANCE:
      Commonly used brief screens for Gambling Disorder appear to be associated with
      good diagnostic accuracy when used in substance use treatment settings. The
      choice of which brief screen to use may best be decided by the needs of the
      clinical setting.

PMID- 25963049
TI  - Duration of US Residence and Obesity Risk in NYC Chinese Immigrants.
AB  - We evaluated whether duration of time in the US is associated with obesity risk
      in NYC Chinese immigrants. We analyzed cross-sectional survey data on 2072 men
      and women. Duration of US residence was categorized into <=5, 6-15, and 15 years
      and over. Obesity was defined using WHO Asian standards: BMI of 27.5 kg/m(2) or
      greater. Diet and physical activity (PA) were assessed as potential explanatory
      variables. After adjusting for covariates, increased time in the US was
      associated with an increased obesity risk (OR 1.49; 95 % CI 1.06, 2.08 for 15
      years or more vs. <=5 years); and in separate analysis, with having reported no
      work related PA (OR 0.76; 95 % CI 0.59, 0.99). Findings suggest that increased
      time living in the US is associated with an increased obesity risk, a finding
      possibly explained by a shift to more sedentary lifestyle characteristic of the
      transition of immigrants to the US.

PMID- 25963050
TI  - A Multilevel Approach on Self-Reported Dental Caries in Subjects of Minority
      Ethnic Groups: A Cross-Sectional Study of 6440 Adults.
AB  - Regional contextual factors and dental caries using multilevel modeling related
      to adults in minority ethnic groups have been scantily explored. The influence of
      the socioeconomic context on self-reported dental caries (SRDC) in individuals of
      minority ethnic groups (IEG) in Colombia was studied. Data from the 2007 National
      Public Health Survey were collected in 34,843 participants of the population. The
      influence of different factors on SRDC in IEG was investigated with logistic and
      multilevel regression analyses. A total of 6440 individuals belonged to an ethnic
      group. Multilevel analysis showed a significant variance in SRDC that was smaller
      in IEG level than between states. Multilevel multivariate analysis also
      associated SRDC with increasing age, lower education level, last dental visit >1
      year, unmet dental need and low Gross Domestic Product (GDP). Minority ethnic
      groups were at risk to report higher dental caries, where low GDP was an
      important variable to be considered. 

PMID- 25963051
TI  - Traditional vs. non-traditional healing for minor and major morbidities in India:
      uses, cost and quality comparisons.
AB  - OBJECTIVES: To examine the uses, cost and quality of care of traditional healing
      for short-term morbidities and major morbidities in India and to compare them
      with the non-traditional healing. METHODS: We used data from a nationally
      representative survey, the India Human Development Survey (2004-2005) and
      descriptive as well as bivariate analyses for the examination. RESULTS: Use of
      traditional healing is much less common than use of non-traditional healing in
      both rural and urban areas and across all socio-economic and demographic
      characteristics; it is slightly more common in rural than urban areas for short
      term morbidities. Use of traditional healing is relatively more frequent for
      cataract (especially in rural areas), leprosy, asthma, polio, paralysis, epilepsy
      and mental illnesses; its total cost of care and mean waiting time (in the health
      facility) are substantially lower than for non-traditional healing. Among
      patients who use both traditional and non-traditional healing, a relatively
      higher proportion use traditional healing complemented by non-traditional healing
      for short-term illnesses, but vice versa for major morbidities. CONCLUSION: This
      is the first study which has investigated at the national level the uses,
      complementarities, cost and quality aspects of traditional and non-traditional
      healing in India. Traditional healing is more affordable and pro-poor. Relatively
      higher use of traditional healing in patients from poorly educated as well as
      poor households and suffering from diseases, such as, epilepsy and mental
      illnesses; and higher demand for traditional healing for the above diseases
      highlight the need for research/policy reorientation in India.

PMID- 25963052
TI  - MSCA: a spectral comparison algorithm between time series to identify protein
      protein interactions.
AB  - BACKGROUND: The interactions between pathogen proteins and their hosts allow
      pathogens to manipulate host cellular mechanisms to their advantage. The
      identification of host proteins that are targeted by virulent pathogen proteins
      is crucial to increase our understanding of infection mechanisms and to propose
      new therapeutics that target pathogens. Understanding the virulence mechanisms of
      pathogens requires a detailed molecular description of the proteins involved, but
      acquiring this knowledge is time consuming and prohibitively expensive.
      Therefore, we develop a statistical method based on hypothesis testing to compare
      the time series obtained from conversion of the physicochemical characteristics
      of the amino acids that form the primary structure of proteins and thus to
      propose potential functional relation between proteins. We called this algorithm
      the multiple spectral comparison algorithm (MSCA); the MSCA was inspired by the
      BLASTP tool and was implemented in R code. The algorithm compares and relates
      multiple time series according to their spectral similarities, and the biological
      relation between them could be interpreted as either a similar function or
      protein-protein interaction (PPI). RESULTS: A simulation study showed that the
      MSCA works satisfactorily well when we compare unequal time series generated from
      ARMA processes because its power was close to 1. The MSCA presented a 70% average
      accuracy of detecting protein interactions using a threshold of 0.7 for our
      spectral measure, indicating that this algorithm could predict novel PPIs and
      pathogen-host interactions (PHIs) with acceptable confidence. The MSCA also was
      validated by its identification of well-known interactions of the human proteins
      MAGI1, SCRIB and JAK1, as well as interactions of the virulence proteins ROP16,
      ROP18, ROP17 and ROP5. We verified the spectral similarities for human
      intraspecific PPIs and PHIs that were previously demonstrated experimentally by
      other authors. We suggest that human GBP (GTPase group induced by interferon) and
      the CREB transcription factor family could be human substrates for the complex of
      ROP18, ROP17 and ROP5. CONCLUSIONS: Using multiple-hypothesis testing between the
      spectral densities of a set of unequal time series, we developed an algorithm
      that is able to identify the similarities or interactions between a set of
      proteins.

PMID- 25963053
TI  - Post-radiotherapy prostate biopsies reveal heightened apex positivity relative to
      other prostate regions sampled.
AB  - BACKGROUND AND PURPOSE: Prostate biopsy positivity after radiotherapy (RT) is a
      significant determinant of eventual biochemical failure. We mapped pre- and post
      treatment tumor locations to determine if residual disease is location-dependent.
      MATERIALS AND METHODS: There were 303 patients treated on a randomized
      hypofractionation trial. Of these, 125 underwent prostate biopsy 2-years post-RT.
      Biopsy cores were mapped to a sextant template, and 86 patients with both pre
      /post-treatment systematic sextant biopsies were analyzed. RESULTS: The
      pretreatment distribution of positive biopsy cores was not significantly related
      to prostate region (base, mid, apex; p=0.723). Whereas all regions post-RT had
      reduced positive biopsies, the base was reduced to the greatest degree and the
      apex the least (p=0.045). In 38 patients who had a positive post-treatment
      biopsy, there was change in the rate of apical positivity before and after
      treatment (76 vs. 71%; p=0.774), while significant reductions were seen in the
      mid and base. CONCLUSION: In our experience, persistence of prostate tumor cells
      after RT increases going from the base to apex. MRI was used in planning and
      image guidance was performed daily during treatment, so geographic miss of the
      apex is unlikely. Nonetheless, the pattern observed suggests that attention to
      apex dosimetry is a priority.

PMID- 25963054
TI  - Highly efficient microfluidic sorting device for synchronizing developmental
      stages of C. elegans based on deflecting electrotaxis.
AB  - C. elegans as a powerful model organism has been widely used in fundamental
      biological studies. Many of these studies frequently need a large number of
      different stage-synchronized worms due to the stage-specific features of C.
      elegans among 4 distinct larval stages and the adult stage. In this work, we
      present an interesting and cost-effective microfluidic approach to realize
      simultaneous sorting of C. elegans of different developmental stages by
      deflecting electrotaxis. The microfluidic device was fabricated using PDMS
      consisting of symmetric sorting channels with specific angles, which was further
      hybridized to an agarose plate. While applying an electric field, different
      stages of C. elegans would crawl to the negative pore with different angles due
      to their deflecting electrotaxis. Thus, the worms were separated and synchronized
      by stages. lon-2 mutant was further used to study this electrotactic response and
      the results indicated that the body size plays a key role in determining the
      deflecting angle in matured adult worms. In addition to discriminating wild-type
      hermaphrodites, it could also be employed to sort mutants with abnormal
      development sizes and males. Therefore, our device provided a versatile and
      highly efficient platform for sorting C. elegans to meet the requirement of large
      numbers of different stage-synchronized worms. It can also be further used to
      investigate the neuronal basis of deflecting electrotaxis in worms. 

PMID- 25963055
TI  - Effect of IQoro(R) training in hiatal hernia patients with misdirected swallowing
      and esophageal retention symptoms.
AB  - CONCLUSION: Misdirected swallowing can be triggered by esophageal retention and
      hiatal incompetence. The results show that oral IQoro(R) screen (IQS) training
      improves misdirected swallowing, hoarseness, cough, esophageal retention, and
      globus symptoms in patients with hiatal hernia. OBJECTIVES: The present study
      investigated whether muscle training with an IQS influences symptoms of
      misdirected swallowing and esophageal retention in patients with hiatal hernia.
      METHODS: A total of 28 adult patients with hiatal hernia suffering from
      misdirected swallowing and esophageal retention symptoms for more than 1 year
      before entry to the study were evaluated before and after training with an IQS.
      The patients had to fill out a questionnaire regarding symptoms of misdirected
      swallowing, hoarseness, cough, esophageal retention, and suprasternal globus,
      which were scored from 0-3, and a VAS on the ability to swallow food. The effect
      of IQS traction on diaphragmatic hiatus (DH) pressure was recorded in 12 patients
      with hiatal hernia using high resolution manometry (HRM). RESULTS: Upon entry
      into the study, misdirected swallowing, globus sensation, and esophageal
      retention symptoms were present in all 28 patients, hoarseness in 79%, and cough
      in 86%. Significant improvement was found for all symptoms after oral IQS
      training (p < 0.001). Traction with an IQS resulted in a 65 mmHg increase in the
      mean HRM pressure of the DH.

PMID- 25963056
TI  - Bladder septum: an unexpected finding on cystoscopy in a patient with mixed
      urinary incontinence.

PMID- 25963057
TI  - The Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12):
      validation of the Dutch version.
AB  - OBJECTIVES AND HYPOTHESIS: To establish the reliability and validity of the Dutch
      version of the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire
      (PISQ-12) in women with pelvic floor dysfunction. METHODS: The PISQ-12 was
      translated into Dutch following a standardized translation process. A group of
      124 women involved in a heterosexual relationship who had had symptoms of urinary
      incontinence, fecal incontinence and/or pelvic organ prolapse for at least 3
      months were eligible for inclusion. A reference group was used for assessment of
      discriminative ability. Data were analyzed for internal consistency,
      reproducibility, construct validity, responsiveness, and interpretability. An
      alteration was made to item 12 and was corrected for during the analysis.
      RESULTS: The patient group comprised 70 of the 124 eligible women, and the
      reference group comprised 208 women from a panel representative of the Dutch
      female population. The Dutch PISQ-12 showed an adequate internal consistency with
      a Cronbach's alpha of 0.57 - 0.69, increasing with correction for item 12 to 0.69
      - 0.75, for the reference and patient group, respectively. Scores in the patient
      group were lower (32.6 +/- 6.9) than in the reference group (36.3 +/- 4.8; p =
      0.0001), indicating a lower sexual function in the patient group and good
      discriminative ability. Reproducibility was excellent with an intraclass
      correlation coefficient for agreement of 0.93 (0.88 - 0.96). A positive
      correlation was found with the Short Form-12 Health Survey (SF-12) measure
      representing good criterion validity. Due to the small number of patients who had
      received treatment at the 6-month follow-up, no significant responsiveness could
      be established. CONCLUSIONS: This study showed that the Dutch version of the PISQ
      12 has good validity and reliability. The PISQ-12 will enable Dutch physicians to
      evaluate sexual dysfunction in women with pelvic floor disorders.

PMID- 25963058
TI  - Postoperative groin pain and success rates following transobturator midurethral
      sling placement: TVT ABBREVO(r) system versus TVTTM obturator system.
AB  - INTRODUCTION AND HYPOTHESIS: Placement of a transobturator midurethral sling
      (MUS) is the standard surgical treatment for stress urinary incontinence. Most
      recent MUS procedures have been poorly evaluated. We compared the results using a
      "new" device expected to reduce postoperative pain, the TVT ABBREVO(r) system
      (TVT-Abb), with those using the TVTTM obturator system (TVT-O). METHODS: This was
      a retrospective study comparing the use of the TVT-Abb (in 50 patients) and the
      TVT-O (in 50 patients). The main outcomes were the amount of postoperative pain,
      the success rate (no reported urinary leakage and negative cough test) with both
      MUS procedures, and the prevalence of complications. RESULTS: The mean follow-up
      time was 12 months. The preoperative characteristics of the two groups were
      comparable. There was less postoperative pain (VAS, 0 to 100) in the TVT-Abb
      group than in the TVT-O group (12.2 vs. 24.4, p < 0.01). However, at 6 weeks
      after surgery there was no significant difference between the two groups (p =
      0.32). The incidence of de novo bladder outlet obstruction symptoms was similar
      in the TVT-Abb group and the TVT-O group (8 % vs. 12 %, p = 0.74). The
      prevalences of perioperative and postoperative complications (bladder/urethral
      injury, haemorrhage) in the two groups were equal. The success rates were similar
      at 12 months after surgery (88 % vs. 78 %, p = 0.29). CONCLUSIONS: The success
      rates with TVT-Abb and TVT-O were equal at 12 months after surgery, but there was
      less immediate postoperative pain with TVT-Abb.

PMID- 25963059
TI  - Bowel vaginoplasty in children and young women: an institutional experience with
      55 patients.
AB  - INTRODUCTION AND HYPOTHESIS: Absence of a vagina owing to congenital Mullerian
      defects or other acquired causes requires reconstruction of the female genital
      passage. We present our experience using various bowel segments. METHODS: Bowel
      vaginoplasty was performed in 55 patients from January 2004 through May 2014 for
      cervicovaginal atresia (20), Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome (20),
      distal vaginal atresia (8), cloaca (2), cervical atresia (1), complex urogenital
      sinus (1), transverse vaginal septum (1), rhabdomyosarcoma of the vagina (1), and
      traumatic stricture of the vagina (1). The bowel segments used were sigmoid (50),
      ileum (2), anorectovestibular fistula ( 2), and loop rectovaginoplasty (1).
      RESULTS: Thirty-nine patients who had the proximal vagina or uterus anastomosed
      to the bowel segment reported regular menstrual flows. Three patients are
      sexually active with satisfactory coital function. None of our patients developed
      pyometra. Five patients had neovaginal mucosal prolapse. Two patients had severe
      stenosis requiring excision of the neovagina. Seven patients had mild stenosis
      requiring dilatations in 6 patients and V-Y meatoplasty for 1 patient. One
      patient had a descending colon anastomotic leak requiring a diversion ileostomy.
      CONCLUSIONS: Genital reconstruction with bowel vaginoplasty is a highly skilled
      operation that provides a durable and lubricated replacement of the vagina with
      good outcomes. Utero-coloneovaginoplasty is a safe procedure preserving the
      menstrual flow in patients with a functional uterine fundus.

PMID- 25963060
TI  - The failed idea of a "gold standard".

PMID- 25963061
TI  - Systematic reviews of apical prolapse surgery: are we being misled down a
      dangerous path?

PMID- 25963062
TI  - Immunogenicity of biologic treatments for psoriasis: therapeutic consequences and
      the potential value of concomitant methotrexate.
AB  - The five biologic agents approved for the treatment of psoriasis-etanercept,
      infliximab, adalimumab, ustekinumab, and secukinumab-have been transformative in
      the clinical management of severe forms of the disease. However, a significant
      number of patients fail to respond to these agents or experience a loss of
      efficacy over time, which may be attributable to the development of antidrug
      antibodies (ADAs). Increasing evidence, primarily in the context of rheumatoid
      arthritis or other chronic inflammatory diseases, suggests that concomitant
      administration of methotrexate may prevent or diminish the development of ADAs,
      thereby improving response rates. However, methotrexate is infrequently
      coadministered with biologic agents in patients with psoriasis, and the potential
      benefits of this strategy in the context of psoriasis are largely unexplored. In
      this review, we discuss clinical studies regarding the development and
      consequences of antibodies targeting biologic agents used in the treatment of
      psoriasis and present key findings describing the potential role of methotrexate
      as an inhibitor of immunogenicity. We also discuss clinical considerations
      pertaining to the use of methotrexate as a tool to reduce immunogenicity, and
      encourage further investigation into potential techniques to optimize this
      treatment approach in patients with psoriasis. 

PMID- 25963064
TI  - Improvement of Ventricular-Arterial Coupling in Elderly Patients with Heart
      Failure After Beta Blocker Therapy: Results from the CIBIS-ELD Trial.
AB  - The interaction between the heart and the arterial system (ventricular-arterial
      coupling - VA) is an important determinant of cardiovascular performance.
      Vascular stiffness (Ea) and left ventricular (LV) endsystolic stiffness (Elv)
      augment with age and in heart failure (HF). Beta blockers (BB) are recommended
      therapy for patients with HF. However, data about the effects of BB on VA
      coupling are scarce. AIMS OF THE STUDY: TO ASSESS: 1) changes in VA after BB
      therapy; 2) interactions between VA and LV functions, 3) predictive factors
      influencing VA change. METHODS: Eight hundred seventy-seven elderly patients with
      HF (aged >= 65, NYHA >= II, LV ejection fraction (LVEF) <= 45%), treated with BB
      according to the CIBIS-ELD protocol of up-titration, underwent Doppler
      echocardiography with clinical and laboratory assessment before and after 12
      weeks of BB. VA coupling was calculated as Ea/Elv ratio. RESULTS: Ventriculo
      arterial interaction improved after 12 weeks of BB in elderly patients with HF.
      Values of Ea significantly decreased from 2.73 +/- 1.16 to 2.40 +/- 1.01, p <
      0.001, resulting in a VA level close to the optimal range i.e. from 1.70 +/- 1.05
      (1.46) to 1.50 +/- 0.94 (1.29), p < 0.001. A similar degree of VA change was
      found in the patients with ischemic and non-ischemic HF after the treatment.
      Improvement in the clinical stage of HF closely correlated with VA coupling
      change after BB (p = 0.006). The strongest predictor of VA coupling alteration
      during BB was the improvement in global LVEF (p < 0.001) followed by the age of
      patients (p = 0.014). CONCLUSIONS: The beneficial effect of BB in elderly
      patients with HF was achieved by optimizing VA coupling close to recommended
      range, associated with an improvement in LVEF and contractility.

PMID- 25963063
TI  - Expression and localization of epithelial stem cell and differentiation markers
      in equine skin, eye and hoof.
AB  - BACKGROUND: The limited characterization of equine skin, eye and hoof epithelial
      stem cell (ESC) and differentiation markers impedes the investigation of the
      physiology and pathophysiology of these tissues. HYPOTHESIS/OBJECTIVES: To
      characterize ESC and differentiation marker expression in epithelial tissues of
      the equine eye, haired skin and hoof capsule. METHODS: Indirect
      immunofluorescence microscopy and immunoblotting were used to detect expression
      and tissue localization of keratin (K) isoforms K3, K10, K14 and K124, the
      transcription factor p63 (a marker of ESCs) and phosphorylated p63 [pp63; a
      marker of ESC transition to transit-amplifying (TA) cell] in epithelial tissues
      of the foot (haired skin, hoof coronet and hoof lamellae) and the eye (limbus and
      cornea). RESULTS: Expression of K14 was restricted to the basal layer of
      epidermal lamellae and to basal and adjacent suprabasal layers of the haired
      skin, coronet and corneal limbus. Coronary and lamellar epidermis was negative
      for both K3 and K10, which were expressed in the cornea/limbus epithelium and
      haired skin epidermis, respectively. Variable expression of p63 with relatively
      low to high levels of phosphorylation was detected in individual basal and
      suprabasal cells of all epithelial tissues examined. CONCLUSIONS: To the best of
      the author's knowledge, this is the first report of the characterization of
      tissue-specific keratin marker expression and the localization of putative
      epithelial progenitor cell populations, including ESCs (high p63 expression with
      low pp63 levels) and TA cells (high expression of both p63 and pp63), in the
      horse. These results will aid further investigation of epidermal and corneal
      epithelial biology and regenerative therapies in horses.

PMID- 25963065
TI  - In Vivo Kinetics of Mesenchymal Stem Cells Transplanted into the Knee Joint in a
      Rat Model Using a Novel Magnetic Method of Localization.
AB  - We have developed a magnetic system for targeting cells in minimally invasive
      cell transplantation. Magnetically labeled MSCs (m-MSCs) with nanoscale iron
      particles can be guided into the desired region by magnetic force from an
      extracorporeal device. We reported that magnetic targeting of m-MSCs enhances
      cartilage repair in a mini-pig model. However, the detailed kinetics of these
      magnetically targeted m-MSCs remain unknown. For clinical use, this aspect should
      be clarified from a safety standpoint. We therefore investigated the spatial and
      temporal distribution of the fluorescently-labeled m-MSCs transplanted into the
      knee joint using in vivo fluorescence combined with three-dimensional computed
      tomographic imaging in a rat model. Although the intraarticularly injected m-MSCs
      were spread throughout the joint cavity in the absence of magnetic force, the
      magnetic force caused the injected m-MSCs to accumulate around the chondral
      lesion. Further examinations including ex vivo imaging, histological assessments
      and reverse transcription polymerase chain reaction revealed that transplanted
      MSCs were not present in any major organs after intraarticular administration,
      regardless of magnetic targeting. Our data suggest that m-MSCs can be accumulated
      efficiently into a chondral lesion using our magnetic targeting system, while
      none of the intraarticularly transplanted MSCs migrate to other major organs. 

PMID- 25963067
TI  - Systematic Review: Impact of Interferon-based Therapy on HCV-related
      Hepatocellular Carcinoma.
AB  - Hepatitis C virus (HCV) is the leading cause of hepatocellular carcinoma (HCC),
      and several antiviral agents are available for the treatment of chronic HCV
      infection. However, the impact of antiviral therapy on the long-term outcomes of
      HCV-related HCC patients remains inconclusive. We aimed to examine the impact of
      antiviral therapy on the long-term outcomes of HCV-related HCC patients. We
      conducted a systematic review using PRISMA guidelines to identify trials and
      English-language literature from PubMed, Ovid MEDLINE, Scopus and the Cochrane
      Library database till August 2014. Randomized trials of antiviral treatments
      examining the effects of antiviral therapy on CHC patients and HCV-related HCC
      patients were screened and selected. We identified 6 trials evaluated the
      effectiveness of interferon (IFN)-alfa treatment, 3 studies examined pegylated
      interferon-alfa treatment, and 2 studies examined IFN-beta treatment. IFN-based
      therapy may decrease HCC incidence in HCV cirrhotic patients after a >5-year
      follow-up, improve liver reserve, decrease HCC recurrence rate, and increase
      survival rate in HCV-related HCC patients after curative HCC therapy. In
      conclusion, IFN-based therapy is beneficial and may be recommended in the
      management of HCV-related HCC patients who are IFN eligible. 

PMID- 25963066
TI  - Age-related structural changes in upper extremity muscle tissue in a nonhuman
      primate model.
AB  - BACKGROUND: Longitudinal studies of upper extremity aging in humans include
      logistical concerns that animal models can overcome. The vervet is a promising
      species with which to study aging-related processes. However, age-related changes
      in upper extremity muscle structure have not been quantified in this species.
      This study measured age-related changes to muscle structure, examined
      relationships between muscle structure and measures of physical performance, and
      evaluated the presence of rotator cuff tears. METHODS: Muscle structure (volume,
      optimal fiber length, and physiologic cross-sectional area (PCSA)) of 10 upper
      extremity muscles was quantified from the right upper limb of 5 middle-aged and 6
      older adult female vervets. RESULTS: Total measured PCSA was smaller (P = .001)
      in the older adult vervets than in the middle-aged vervets. Muscle volume
      reduction predominate the age-related reductions in PCSA. Total measured PCSA was
      not correlated to any measures of physical performance. No rotator cuff tears
      were observed. Supraspinatus volume was relatively larger and deltoid volume
      relatively smaller in the vervet compared with a human. CONCLUSIONS: The vervet
      is an appropriate translational model for age-related upper extremity muscle
      volume loss. Functional measures were not correlated to PCSA, suggesting the
      vervets may have enough strength for normal function despite loss of muscle
      tissue. Reduced relative demand on the supraspinatus may be responsible for the
      lack of naturally occurring rotator cuff tears.

PMID- 25963068
TI  - Primary Sjogren's syndrome and occupational risk factors: A case-control study.
AB  - OBJECTIVES: A case-control study was carried out to investigate the relation
      between primary Sjogren's syndrome (pSS) and occupational exposure. METHODS: One
      hundred seventy five cases of pSS followed up into the internal medicine
      departments of three French university hospitals from 2010 to 2013 were included.
      For each case, two age and gender matched controls were selected during the same
      period in the same departments. Occupational exposure was assessed
      retrospectively by industrial hygienists and occupational practitioners. Exposure
      to occupational factors such as organic solvents or silica was investigated using
      semiquantitative estimates of exposure. An exposure score was calculated for each
      subject based on probability, intensity, daily frequency, and duration of
      exposure for each period of employment. The final cumulative exposure score was
      obtained, taking into account all periods of employment. RESULTS: Significant
      associations with pSS were observed for dichloromethane (OR 9.28, 95%CI 2.60
      33.03), perchlorethylene (OR 2.64, 95%CI 1.20-5.77) chlorinated solvents (OR
      2.95, 95%CI 1.77-4.93), benzene (OR 3.30, 95%CI 1.07-10.26), toluene (OR 4.18
      95%CI 1.41-12.43), white spirit (OR 3.60, 95%CI 1.39-9.33), aromatic solvents (OR
      3.03, 95%CI 1.41-6.50) and any types of solvents (OR 2.76, 95%CI 1.70-4.47). Risk
      of pSS was significantly associated with a high cumulative exposure score of
      occupational exposure to toluene (OR 4.69, 95%CI 1.42-15.45), white spirit (OR
      3.30, 95%CI 1.07-10.26), aromatic solvents (OR 2.50, 95%CI 1.06-5.91) and any
      types of solvents (OR 2.25, 95%CI 1.20-4.22). CONCLUSION: This work suggests the
      influence of occupational risk factors in the occurrence of pSS.

PMID- 25963069
TI  - Impact of insecticide exposure on the predation activity of the European earwig
      Forficula auricularia.
AB  - The European earwig Forficula auricularia is an effective predator in apple
      orchards. It is therefore crucial to study whether insecticides affect this
      natural pest control agent. Predation activity, i.e., the number of aphids eaten
      in 24 h, was determined under laboratory conditions after exposure of fourth
      instar nymphs and adult earwigs to widely used insecticides (acetamiprid,
      chlorpyrifos-ethyl, deltamethrin, and spinosad), which were applied at the normal
      application rates. Inhibition of acetylcholinesterase and carboxylesterase
      activities were also measured as indicators of pesticide exposure. Predation
      activity decreased significantly in nymphs exposed to spinosad (62%) and
      chlorpyrifos-ethyl (98%) compared with controls. A similar response was found for
      both esterase activities. Spinosad had a stronger effect on AChE (-33%) whereas
      chlorpyrifos-ethyl affected CbE activity preferentially (-59%). Spinosad (20% of
      controls), acetamiprid (28%), and chlorpyrifos-ethyl (66%) also significantly
      decreased the predation behavior of adult male but not female (5 to 40%) earwigs.
      Adult AChE and CbE activities were also significantly reduced (28 to 67% of
      controls) in pesticide-exposed earwigs. Our results suggest that earwigs should
      be included in the environmental risk assessment framework for authorization of
      newly marketed plant protection products. Their predation behavior appears to be
      a sensitive and complementary biomarker.

PMID- 25963070
TI  - Ecological, morphological, and histological studies on Blaps polycresta
      (Coleoptera: Tenebrionidae) as biomonitors of cadmium soil pollution.
AB  - Soil pollution in Egypt became far more serious than before due to either the
      heavy usage of different toxic pesticides or aerosol deposition of industrial
      pollutants. The present mentioned ground beetle, Blaps polycresta Tschinkel 1975
      (Coleoptera: Tenebrionidae), showed ecological, morphological, and histological
      alterations in adult insects as biomonitors. Two cultivated sites (reference and
      polluted) were chosen for sampling the insects. The results indicated a
      significant increase in soil cadmium concentration of the polluted site leading
      to sex-specific difference in cadmium accumulation in gonads and alimentary canal
      of insects that being higher in males than females. The cadmium pollution leads
      significantly to a decrease in population density, a reduction in body weight, an
      increase in mortality rate, and an increase in sex ratio of the insects. The
      results also revealed a striking decrease in body length of the polluted insects
      with a marked increase in the percentage of deformed gonads and alimentary canal
      of both sexes. Some histopathological alterations were also recorded in testis,
      ovary, and midgut of the polluted insects. Our results confirmed that beetles are
      a good bioindicator for soil pollution, and the different studied parameters
      could be easily employed as sensitive monitors for cadmium soil pollution. 

PMID- 25963071
TI  - Determination of natural and synthetic glucocorticoids in effluent of sewage
      treatment plants using ultrahigh performance liquid chromatography-tandem mass
      spectrometry.
AB  - A sensitive and comprehensive analytical method for glucocorticoids (GCs) in
      water samples was developed and applied to effluent of sewage treatment plants
      (STPs). In the present study, totally 10 natural and synthetic GCs, including
      cortisol, betamethasone valerate, clobetasol propionate, clobetasone butyrate,
      difluprednate, betamethasone, dexamethasone, betamethasone dipropionate,
      methylprednisolone, and prednisolone, were targeted. Analytes were extracted and
      concentrated using an OASIS HLB solid phase extraction cartridge. Chromatographic
      separation and quantification were achieved using an ultrahigh performance liquid
      chromatograph coupled with a tandem mass spectrometer (UHPLC-MS/MS). Method
      detection limits were 0.05 to 0.89 ng/L, which were 1-2 orders of magnitude more
      sensitive than in the previous reports. Cortisol was detected in more than half
      of (27 out of 50) analyzed effluent samples at concentrations in the range of ND
      1.36 ng/L, indicating continuous discharge of natural GC via STP effluent. On the
      other hand, dexamethasone + betamethasone, prednisolone, betamethasone valerate,
      and clobetasol propionate were detected in 25, 8, 20, and 9 samples among 50
      effluent samples, respectively, suggesting not extreme but significant
      administration of synthetic GCs. 

PMID- 25963072
TI  - Comment on "Artificial neural network modelling of biological oxygen demand in
      rivers at the national level with input selection based on Monte Carlo
      simulations A. Siljic & D. Antanasijevic & A. Peric-Grujic & M. Ristic & V.
      Pocajt. Environ Sci Pollut Res (2014) 22: 4230-4241".

PMID- 25963073
TI  - MYB rearrangement and clinicopathologic characteristics in head and neck adenoid
      cystic carcinoma.
AB  - OBJECTIVES: Salivary gland adenoid cystic carcinoma (ACC) is rare, aggressive,
      and challenging to treat. Many ACCs have a t(6;9) chromosomal translocation
      resulting in a MYB-NFIB fusion gene, but the clinical significance is unclear.
      The purposes of this study were to describe the clinicopathologic factors
      impacting survival and to determine the prevalence and clinical significance of
      MYB-NFIB fusion. STUDY DESIGN: Case series. METHODS: Medical records of patients
      treated for ACC of the head and neck from 1974 to 2011 were reviewed and
      clinicopathologic data recorded. Fluorescence in situ hybridization (FISH) was
      used to detect MYB rearrangement in archival tumor tissue as a marker of MYB-NFIB
      fusion. RESULTS: One hundred fifty-eight patients were included, with median
      follow-up 75.1 months. Median overall survival was 171.5 months (95% confidence
      interval [CI] = 131.9-191.6), and median disease-free survival was 112.0 months
      (95% CI = 88.7-180.4). Advanced stage was associated with decreased overall
      survival (adjusted ptrend  < 0.001), and positive margins were associated with
      decreased disease-free survival (adjusted hazard ratio [aHR] = 8.80, 95% CI =
      1.25-62.12, P = 0.029). Ninety-one tumors were evaluable using FISH, and 59 (65%)
      had evidence of a MYB-NFIB fusion. MYB-NFIB positive tumors were more likely than
      MYB-NFIB negative tumors to originate in minor salivary glands (adjusted
      prevalence ratios = 1.51, 95% CI = 1.07-2.12, P = 0.019). MYB-NFIB tumor status
      was not significantly associated with disease-free or overall survival (hazard
      ratio [HR] = 1.53, 95% CI = 0.77-3.02, P = 0.22 and HR = 0.91, 95% CI = 0.46
      1.83, P = 0.80, respectively, for MYB-NFIB positive compared with MYB-NFIB
      negative tumors). CONCLUSION: Stage and margin status were important prognostic
      factors for ACC. Tumors with evidence of MYB-NFIB fusion were more likely to
      originate in minor salivary glands, but MYB-NFIB tumor status was not
      significantly associated with prognosis. LEVEL OF EVIDENCE: 4.

PMID- 25963074
TI  - Retinal nerve fiber layer and ganglion cell complex thicknesses measured with
      spectral-domain optical coherence tomography in eyes with no light perception due
      to nonglaucomatous optic neuropathy.
AB  - PURPOSE: To measure retinal nerve fiber layer thickness (RNFLT) and ganglion cell
      complex thickness (GCCT) in eyes with no light perception due to nonglaucomatous
      optic neuropathy using spectral-domain optical coherence tomography. METHODS:
      Fourteen eyes of 14 patients (9 women, 5 men; mean age 56.0 +/- 16.6 (standard
      deviation) years] with no light perception due to optic neuropathy were recruited
      to this retrospective study. Only clinically stable eyes were included. Eyes were
      imaged at least 6 months after the onset of the disease. Five patients lost light
      perception due to traumatic optic neuropathy, four patients had ischemic optic
      neuropathy, two patients had optic neuritis, two patients had compressive optic
      neuropathy, and one patient had optic nerve atrophy. Global and quadrant RNFLTs
      were measured with the Cirrus HD-optical coherence tomography (OCT) system;
      global and hemisphere GCCTs were measured by spectral-domain OCT (RTVue OCT
      system). Only reliable OCT images were used for further analysis. RESULTS:
      Reliable RNFL images were obtained in 12 eyes, and reliable GCC images were
      obtained in 11 eyes. Global, superior, temporal, inferior, and nasal RNFLT were
      57.5 +/- 6.7, 60.6 +/- 7.6, 54.1 +/- 11.2, 59.7 +/- 9.5, and 55.6 +/- 7.4 um,
      respectively. Global, superior, and inferior GCC thicknesses were 68.8 +/- 9.6,
      70.7 +/- 12.2, and 67.8 +/- 8.8 um, respectively. CONCLUSIONS: A considerable
      proportion of RNFL and GCC remained in eyes with no light perception vision.
      Clinicians should take this into account when evaluating the severity of optic
      neuropathy from OCT-measured RNFLT and GCCT.

PMID- 25963075
TI  - Clinical Risk Factors for Upper Gastrointestinal Bleeding after Percutaneous
      Coronary Intervention: A Single-Center Study.
AB  - BACKGROUND/AIMS: Percutaneous coronary intervention (PCI) is often performed
      therapeutically, and antithrombotic treatment is required for at least 12 months
      after stent implantation. However, the development of post-PCI upper
      gastrointestinal bleeding (UGIB) increases morbidity and mortality. We
      investigated the incidence and risk factors for UGIB in Korean patients within 1
      year after PCI. METHODS: The medical records of 3,541 patients who had undergone
      PCI between January 2006 and June 2012 were retrospectively reviewed. We
      identified 40 cases of UGIB. We analyzed the incidence and clinical risk factors
      associated with UGIB occurring within 1 year after PCI by comparing the results
      for each case to matched controls. The propensity score matching method using age
      and sex was utilized. RESULTS: UGIB occurred in 40 patients (1.1%). Two
      independent risk factors for UGIB were a history of peptic ulcer disease (odds
      ratio [OR], 12.68; 95% confidence interval [CI], 2.70 to 59.66; p=0.001) and the
      use of anticoagulants (OR, 7.76; 95% CI, 2.10 to 28.66; p=0.002). CONCLUSIONS:
      UGIB after PCI occurred at a rate of 1.1% in the study population. Clinicians
      must remain vigilant for the possibility of UGIB after PCI and should consider
      performing timely endoscopy in patients who have undergone PCI and are suspected
      of having an UGIB.

PMID- 25963076
TI  - Overlooked Management and Risk Factors for Anemia in Patients with Intestinal
      Behcet's Disease in Actual Clinical Practice.
AB  - BACKGROUND/AIMS: Anemia in patients with inflammatory bowel disease significantly
      affects the quality of life. The aim of this study was to investigate the
      frequency of and risk factors for anemia and to describe the management of anemia
      in patients with intestinal Behcet's disease (BD) in actual clinical practice.
      METHODS: We included 64 patients with intestinal BD who visited the outpatient
      clinic of a tertiary referral center in June 2011 and had available laboratory
      data for the subsequent 6 months. RESULTS: Anemia was detected in 26 patients
      (40.6%). After 6 months, anemia was still present in 14 of these patients
      (53.8%). The cause of anemia was investigated in eight patients (30.8%), and oral
      iron supplementation was prescribed to four patients (15.4%). Of these four
      patients, two (50%) recovered completely within 6 months. Anemia was associated
      with a high Disease Activity Index for Intestinal Behcet's Disease (DAIBD,
      p=0.024), erythrocyte sedimentation rate (p=0.003), and C-reactive protein
      (p=0.049) in univariate analysis. In multivariate analysis, the factor predictive
      for anemia in patients with intestinal BD was a higher DAIBD (>=40; odds ratio,
      4.08; 95% confidence interval, 1.21 to 13.71; p=0.023). CONCLUSIONS: Although
      anemia is common in intestinal BD patients, its clinical importance is overlooked
      in daily practice. Moderate to severe disease activity is predictive of anemia.

PMID- 25963077
TI  - Intraductal Ultrasonography without Radiocontrast Cholangiogramin Patients with
      Extrahepatic Biliary Disease.
AB  - BACKGROUND/AIMS: Intraductal ultrasonography (IDUS) has been performed as an
      adjunct to endoscopic retrograde cholangiography (ERC) during radiocontrast
      cholangiography (RC). Radiation exposure during RC poses a health risk to both
      patients and examiners. We evaluated the feasibility of IDUS without RC in
      various extrahepatic biliary diseases. METHODS: IDUS was performed with the
      insertion of an IDUS probe from the papilla of Vater to the confluent portion of
      the common hepatic duct without fluoroscopy. The technical success rate and
      procedure-related complications were evaluated retrospectively. RESULTS: Wire
      guided IDUS without RC was performed in 105 patients. The mean age was 66.5
      years, and 50 (47.6%) were male. The IDUS diagnoses included choledocholithiasis
      (73, 69.5%), benign biliary stricture (11, 10.5%), choledocholithiasis with
      biliary pancreatitis (9, 8.6%), bile duct cancer (5, 4.8%), pancreatic cancer (1,
      0.9%), and others (6, 5.7%). After IDUS, 66 (62.8%) underwent stone removal, 19
      (18.1%) underwent biliary drainage, and 7 (6.6%) underwent brush cytology and
      biopsy. No significant complications such as perforation or severe pancreatitis
      occurred. CONCLUSIONS: IDUS without RC was a feasible and safe approach in
      patients with various extrahepatic biliary diseases. We anticipate a potentially
      important role of IDUS in various ERC procedures because it lacks the hazards of
      RC.

PMID- 25963078
TI  - The Risk of Metachronous Advanced Colorectal Neoplasia Rises in Parallel with an
      Increasing Number of High-Risk Findings at Baseline.
AB  - BACKGROUND/AIMS: Colorectal adenomas that are >=10 mm have villous histology or
      high-grade dysplasia, or that are associated with >=3 adenomas are considered
      high-risk for metachronous advanced neoplasia. We evaluated the cumulative
      incidence of metachronous advanced neoplasia according to the total number of
      high-risk findings detected on baseline colonoscopy. METHODS: This was a
      retrospective cohort study performed in 862 patients who underwent removal of
      colorectal adenomas between 2005 and 2009. At least one surveillance colonoscopy
      had been conducted at Konkuk University Medical Center, Seoul, Korea. RESULTS:
      The cumulative incidence of metachronous advanced neoplasia in patients with 0,
      1, 2, and 3-4 high-risk findings at 1 year were 0.7%, 1.3%, 2.8%, and 8.0%; at 3
      years, those were 5.9%, 11.9%, 15.5%, and 24.7%; and at 5 years, those were 8.5%,
      18.7%, 26.3%, and 37.2%, respectively. In a multivariate model, the risk of
      metachronous advanced neoplasia was significantly higher for the multiple high
      risk findings group when compared with the 0 high-risk findings group (1 high
      risk (+) hazard ratio, 1.86 [95% confidence interval, 1.00-3.44]; 2 high-risk (+)
      1.84 [0.88-3.84]; and 3-4 high-risk (+) 3.29 [1.54-7.01]; ptrend=0.020).
      CONCLUSIONS: The presence of overlapping multiple high-risk findings was
      associated with an increased risk of advanced neoplasia during surveillance.

PMID- 25963079
TI  - Potential Serum Markers for Monitoring the Progression of Hepatitis B Virus
      Associated Chronic Hepatic Lesions to Liver Cirrhosis.
AB  - BACKGROUND/AIMS: To screen for serum protein/peptide biomarkers of hepatitis B
      virus (HBV)-associated chronic hepatic lesions in an attempt to profile the
      progression of HBV-associated chronic hepatic lesions using surface-enhanced
      laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS)
      techniques. METHODS: Using SELDI-TOF MS, serum protein/peptide profiles on the
      CM10 ProteinChip arrays were obtained from a training group including 26 HBV
      associated hepatocellular carcinoma patients with liver cirrhosis (LC), 30 HBV
      associated LC patients, 85 patients at different stages of liver fibrosis, and 30
      asymptomatic HBV carriers. The most valuable SELDI peak for predicting the
      progression to LC in HBV-infected patients was identified. RESULTS: A SELDI peak
      of M/Z 5805 with value for predicting LC in HBV-infected patients was found and
      was identified as a peptide of the C-terminal fraction of the fibrinogen a-chain
      precursor, isoform 1. CONCLUSIONS: The peptide of the C-terminal fraction of the
      fibrinogen alpha-chain precursor, isoform 1 with M/Z 5805, may be a serological
      biomarker for progression to LC in HBV-infected patients.

PMID- 25963080
TI  - Different Strategies for Transpancreatic Septotomy and Needle Knife
      Infundibulotomy Due to the Presence of Unintended Pancreatic Cannulation in
      Difficult Biliary Cannulation.
AB  - BACKGROUND/AIMS: Several precut techniques have been used to gain biliary access
      for difficult cases. The aim of this study was to evaluate the success and
      complication rates of two precut techniques, transpancreatic septotomy (TPS) and
      needle knife infundibulotomy (NKI), in difficult biliary cannulation due to the
      presence of unintended pancreatic cannulation. METHODS: Eighty-six patients who
      failed standard biliary cannulation were included. TPS was performed when we
      failed to achieve biliary access despite 5 minutes of attempted cannulation or
      when more than three attempted unintended pancreatic cannulations occurred. If
      deep cannulation was not achieved within 5 minutes for any duct, NKI was
      performed. If this failed, we crossed over to the other technique in the second
      attempt. RESULTS: The initial total success rate of biliary cannulation was 88.4%
      (86.6% for the TPS group and 94.7% for the NKI group, p=0.447). After crossover
      of the techniques, the final success rate was 95.3%. The complication rate was
      20.9% in patients with TPS and 15.8% in patients with NKI (p=0.753). CONCLUSIONS:
      The use of different strategies based on the presence of unintended pancreatic
      cannulation may help increase the success rate for difficult biliary cannulation
      without increasing complication rates.

PMID- 25963081
TI  - Assessment of Factors Affecting the Usefulness and Diagnostic Yield of Core
      Biopsy Needles with a Side Hole in Endoscopic Ultrasound-Guided Fine-Needle
      Aspiration.
AB  - BACKGROUND/AIMS: A barbed puncture needle with a side hole was recently developed
      to improve sample quality and quantity in endoscopic ultrasound-guided fine
      needle aspiration (EUS-FNA). In this study, we retrospectively assessed the
      usefulness of this puncture needle. METHODS: Factors affecting diagnostic yield,
      safety, and diagnostic accuracy were investigated in 76 patients who
      consecutively underwent EUS-FNA for neoplastic lesions at our hospital between
      January and December 2013. RESULTS: The procedure was successful in all cases;
      the rates of sample collection and determination of the correct diagnosis were
      92.1% and 89.5%, respectively. The mean number of needle passes required for
      diagnosis was 1.1. Complications included mild intraluminal bleeding in two
      patients (2.6%). Multivariate analysis revealed that lesion size (<=20 mm) was
      significantly associated with a decreased chance of determining the correct
      diagnosis. CONCLUSIONS: Core biopsy needles with a side hole are safe and provide
      a satisfactory diagnostic yield. However, the side hole may potentially reduce
      the rate of making the correct diagnosis in small lesions.

PMID- 25963082
TI  - Clinicopathologic Analysis of Proton Pump Inhibitor-Responsive Esophageal
      Eosinophilia in Korean Patients.
AB  - BACKGROUND/AIMS: Proton pump inhibitor-responsive esophageal eosinophilia (PPI
      REE) is a newly recognized form of eosinophilic esophagitis (EoE) that responds
      to PPI therapy. It remains unclear whether PPI-REE represents a subphenotype of
      gastroesophageal reflux disease, a subphenotype of EoE, or its own distinct
      entity. The aim was to evaluate the clinicopathologic features of PPI-REE.
      METHODS: Six patients were diagnosed with PPI-REE based on symptoms, endoscopic
      abnormalities, esophageal eosinophilia with >=15 eosinophils/high-power field,
      and a response to PPI treatment. Symptoms and endoscopic and pathological
      findings were evaluated. RESULTS: The median follow-up duration was 12 months.
      Presenting symptoms included dysphagia, heartburn, chest pain, foreign body
      sensation, acid reflux, and sore throat. All patients had typical endoscopic
      findings of EoE such as esophageal rings, linear furrows, nodularity, and whitish
      plaques. Three patients had a concomitant allergic disorder, and one had reflux
      esophagitis. Four patients exhibited elevated serum IgE, and five had positive
      skin prick tests. All patients experienced symptomatic resolution within 4 weeks
      and histologic resolution within 8 weeks after starting PPI therapy. There was no
      symptomatic recurrence. CONCLUSIONS: PPI therapy induced rapid resolution of
      symptoms and eosinophil counts in patients with PPI-REE. Large-scale studies with
      long-term follow-up are warranted.

PMID- 25963083
TI  - Measurement of Intrahepatic Pressure during Microwave Ablation in an Ex Vivo
      Bovine Liver Model.
AB  - BACKGROUND/AIMS: We experimented with different ablation methods and two types of
      microwave antennas to determine whether microwave ablation (MWA) increases
      intrahepatic pressure and to identify an MWA protocol that avoids increasing
      intrahepatic pressure. METHODS: MWA was performed using either a single-step
      standard ablation or a stepwise increment ablation paired with either a 16-gauge
      (G) 2-cm antenna or a 14G 4-cm antenna. We compared the maximum pressures and
      total ablation volumes. RESULTS: The mean maximum intrahepatic pressures and
      ablation volumes were as follows 16G single-step 37+/-33.4 mm Hg and 4.63 cm(3);
      16G multistep 31+/-18.7 mm Hg and 3.75 cm(3); 14G single-step 114+/-45.4 mm Hg
      and 15.33 cm(3); and 14G multistep 106+/-43.8 mm Hg and 10.98 cm(3). The
      intrahepatic pressure rose during MWA, but there were no statistically
      significant differences between the single and multistep methods when the same
      gauge antennae were used. The total ablation volume was different only in the 14G
      groups (p<0.05). CONCLUSIONS: We demonstrated an increase in intrahepatic
      pressure during MWA. The multistep method may be used to prevent increased
      intrahepatic pressure after applying the proper power.

PMID- 25963084
TI  - Negative Biopsy after Referral for Biopsy-Proven Gastric Cancer.
AB  - BACKGROUND/AIMS: Repeat endoscopy with biopsy is often performed in patients with
      previously diagnosed gastric cancer to determine further treatment plans.
      However, biopsy results may differ from the original pathologic report. We
      reviewed patients who had a negative biopsy after referral for gastric cancer.
      METHODS: A total of 116 patients with negative biopsy results after referral for
      biopsy-proven gastric cancer were enrolled. Outside pathology slides were
      reviewed. Images of the first and second endoscopic examinations were reviewed.
      We reviewed the clinical history from referral to the final treatment. RESULTS:
      Eighty-eight patients (76%) arrived with information about the lesion from the
      referring physician. Among 96 patients with available outside slides, the rate of
      interobserver variation was 24%. Endoscopy was repeated at our institution; 85
      patients (73%) were found to have definite lesions, whereas 31 patients (27%) had
      indeterminate lesions. In the group with definite lesions, 71% of the lesions
      were depressed in shape. The most common cause of a negative biopsy was
      mistargeting. In the group with indeterminate lesions, 94% had insufficient
      information. All patients with adequate follow-up were successfully treated based
      on the findings in the follow-up endoscopy. CONCLUSIONS: A negative biopsy after
      referral for biopsy-proven gastric cancer is mainly caused by mistargeting and
      insufficient information during the referral.

PMID- 25963085
TI  - Comparison of the Effects of Telbivudine and Entecavir Treatment on Estimated
      Glomerular Filtration Rate in Patients with Chronic Hepatitis B.
AB  - BACKGROUND/AIMS: The aim of this study was to evaluate the estimated glomerular
      filtration rate (eGFR) during telbivudine (LdT) versus entecavir (ETV) treatment
      in chronic hepatitis B (CHB) patients with underlying comorbidities such as
      diabetes mellitus (DM), hypertension, and cirrhosis. METHODS: From 2010 to 2012,
      116 CHB patients treated with LdT and 578 treated with ETV were compared in this
      real-practice cohort. The mean changes in eGFR (Modification of Diet in Renal
      Disease [MDRD] formula) from baseline to months 6, 12, and 18 were analyzed using
      a linear mixed model. RESULTS: In LdT-treated patients, the mean eGFR increased
      by 7.6% at month 18 compared with the eGFR at baseline (MDRD formula in
      mL/min/1.73 m(2)). However, in ETV-treated patients, the mean eGFR decreased by
      4.1% at month 18 compared with the eGFR at baseline. In the LdT-treated patients
      with DM, hypertension, cirrhosis or low eGFR <90 mL/min/1.73 m(2), the mean eGFR
      showed a steady improvement, whereas the mean eGFR was reduced in the same
      subgroups of ETV-treated patients. CONCLUSIONS: The eGFR gradually increased over
      time during LdT treatment, especially in patients with mild abnormal eGFR at
      baseline, and in those with DM, hypertension, and cirrhosis, whereas a reduction
      in eGFR was seen with ETV treatment.

PMID- 25963086
TI  - Characteristics of Pediatric Inflammatory Bowel Disease in Korea: Comparison with
      EUROKIDS Data.
AB  - BACKGROUND/AIMS: Pediatric inflammatory bowel disease (IBD) has been increasing
      worldwide. The characteristics of pediatric-onset IBD have mainly been reported
      in Western countries. We investigated the clinical characteristics of pediatric
      IBD in Korea and compared these with the data from the 5-year European
      multicenter study of children with new-onset IBD (EUROKIDS registry). METHODS:
      Children who were diagnosed with IBD between July 1987 and January 2012 were
      investigated at five Korean university hospitals. Their clinical characteristics
      were retrospectively evaluated by medical record review. The results were
      compared with the EUROKIDS data. RESULTS: A total of 30 children with Crohn's
      disease (CD) and 33 children with ulcerative colitis (UC) were enrolled. In
      comparison with the EUROKIDS group, Korean pediatric IBD patients showed a male
      predominance (86.7% vs 59.2%, p=0.002 in CD; 75.8% vs 50%, p=0.003 in UC). Korean
      pediatric CD patients had a higher prevalence of terminal ileal disease (36.7% vs
      16.3%, p=0.004) and perianal disease (33.3% vs 8.2%, p<0.001) than patients in
      the EUROKIDS group. Korean pediatric UC patients had a higher prevalence of
      proctitis than patients in the EUROKIDS group. CONCLUSIONS: Our results suggest
      that the characteristics of Korean pediatric IBD patients and European pediatric
      IBD patients may be different.

PMID- 25963087
TI  - Clinical Implications of the Serum Apelin Level on Portal Hypertension and
      Prognosis of Liver Cirrhosis.
AB  - BACKGROUND/AIMS: Levels of serum apelin (s-apelin), an endogenous ligand for
      angiotensin-like receptor 1, have been shown to be related to hepatic fibrosis
      and hemodynamic abnormalities in preclinical studies. We investigated the
      clinical implications of s-apelin as a noninvasive prognostic biomarker for
      chronic liver disease (CLD). METHODS: From January 2009 to December 2012, 215 CLD
      patients were enrolled and underwent clinical data collection, hepatic venous
      pressure gradient (HVPG) measurement, and liver biopsy. s-apelin was detected
      with a human total apelin enzyme-linked immunosorbent assay kit. All patients
      were prospectively observed during the median follow-up period of 23.0+/-12.9
      months for decompensation and mortality. RESULTS: A total of 42 patients (19.5%)
      died during the follow-up period. s-apelin was significantly correlated with
      measurements of liver stiffness (R2=0.263, p<0.001) and collagen proportional
      area (R2=0.213, p<0.001) measured from liver biopsy tissue and HVPG (R2=0.356,
      p<0.001). In a multivariate analysis using a Cox regression hazard model, s
      apelin was a weakly significant predictor of decompensation (hazard ratio [HR],
      1.002; p<0.001) and mortality (HR, 1.003; p<0.001). CONCLUSIONS: s-apelin showed
      a significant relationship with CLD severity. However, its significance as a
      noninvasive biomarker for disease severity and prognosis was weak.

PMID- 25963089
TI  - Lung cancer: a new generation of EGFR inhibition.

PMID- 25963088
TI  - Esophageal Squamous Cell Carcinoma Patients Have an Increased Risk of Coexisting
      Colorectal Neoplasms.
AB  - BACKGROUND/AIMS: Esophageal squamous cell carcinoma (ESCC) and colorectal
      neoplasms (CRNs) share risk factors. We aimed to investigate whether the CRN risk
      is increased in ESCC patients. METHODS: ESCC patients who underwent a colonoscopy
      within 1 year of diagnosis were retrospectively analyzed. Patients were matched
      13 by age, gender, and body mass index to asymptomatic controls. CRN was defined
      as the histological confirmation of adenoma or adenocarcinoma. Advanced CRN was
      defined as any of the following >=3 adenomas, high-grade dysplasia, villous
      features, tumor >=1 cm, or adenocarcinoma. The risk factors for both CRN and
      advanced CRN were evaluated by univariate and multivariate analyses. RESULTS:
      Sixty ESCC patients were compared with 180 controls. The ESCC group had
      significantly higher numbers of CRNs (odds ratio [OR], 2.311; 95% confidence
      interval [CI], 1.265 to 4.220; p=0.006) and advanced CRNs (OR, 2.317; 95% CI,
      1.185 to 4.530; p=0.013). Significant risk factors for both CRN and advanced CRN
      by multivariate analysis included ESCC (OR, 2.157, 95% CI, 1.106 to 4.070,
      p=0.024; and OR, 2.157, 95% CI, 1.045 to 4.454, p=0.038, respectively) and older
      age (OR, 1.068, 95% CI, 1.032 to 1.106, p<0.001; and OR, 1.065, 95% CI, 1.024 to
      1.109, p=0.002, respectively). CONCLUSIONS: The rates of CRN and advanced CRN are
      significantly increased in ESCC. Colonoscopy should be considered at ESCC
      diagnosis.

PMID- 25963090
TI  - Gastrointestinal cancer: Rationale for metronomic chemotherapy in phase III
      trials.

PMID- 25963092
TI  - Immunotherapy: pembrolizumab-is the writing on the wall for cancer?

PMID- 25963091
TI  - Refining the treatment of NSCLC according to histological and molecular subtypes.
AB  - In the past decade, the characterization of non-small-cell lung cancer (NSCLC)
      into subtypes based on genotype and histology has resulted in dramatic
      improvements in disease outcome in select patient subgroups. In particular,
      molecularly targeted agents that inhibit EGFR or ALK are approved for the
      treatment of NSCLC harbouring genetic alterations in the genes encoding these
      proteins. Although acquired resistance usually limits the duration of response to
      these therapies, a number of new agents have proven effective at tackling
      specific resistance mechanisms to first-generation inhibitors. Large initiatives
      are starting to address the role of biomarker-driven targeted therapy in squamous
      lung cancers, and in the adjuvant setting. Immunotherapy undeniably holds great
      promise and our understanding of subsets of NSCLC based on patterns of immune
      response is continuing to evolve. In addition, efforts are underway to identify
      rare genomic subsets through genomic screening, functional studies, and molecular
      characterization of exceptional responders. This Review provides an overview of
      the key developments in the treatment of NSCLC, and discusses potential
      strategies to further optimize therapy by targeting disease subtypes. 

PMID- 25963093
TI  - Gastrointestinal cancer: Effect of lymphadenectomy on survival in oesophageal
      cancer.

PMID- 25963094
TI  - Integrating biomarkers in colorectal cancer trials in the West and China.
AB  - The discovery of biomarkers that provide information on drug efficacy is
      recognized as essential for successful and cost-effective treatment of cancer.
      However, biomarker discovery is difficult, and requires multiple independent
      studies to identify a target that serves as a suitable predictor of efficacy and
      to ensure appropriate biomarker validation. Clinical trials that are performed,
      sometimes sequentially, in Europe, the USA or Asia, are often similar in their
      design, in part owing to regulatory, marketing, or safety considerations. We
      believe some of these trials offer additional unique opportunities for biomarker
      discovery or validation. There are multiple hurdles to overcome, such as
      homogenous tissue acquisition and analysis, defining and aligning biomarker
      hypotheses across trials, and the need to adapt sample sizes and trial designs.
      Nevertheless, we believe that a collaborative engagement of the academic,
      regulatory and pharmaceutical community can go a long way in addressing these
      issues and producing more-rapid results in the field of personalized medicine. In
      this Perspectives, we describe our views on the current fragmented approach to
      biomarker discovery and validation in relevant trials run within our own regions
      that is, Europe, China, and the USA-and hope this article serves as a base for
      further reflection. 

PMID- 25963095
TI  - Dyrk1A phosphorylates parkin at Ser-131 and negatively regulates its ubiquitin E3
      ligase activity.
AB  - Mutations of parkin are associated with the occurrence of autosomal recessive
      familial Parkinson's disease (PD). Parkin acts an E3 ubiquitin ligase, which
      ubiquitinates target proteins and subsequently regulates either their steady
      state levels through the ubiquitin-proteasome system or biochemical properties.
      In this study, we identify a novel regulatory mechanism of parkin by searching
      for new regulatory factors. After screening human fetal brain using a yeast two
      hybrid assay, we found dual-specificity tyrosine-(Y)-phosphorylation-regulated
      kinase 1A (Dyrk1A) as a novel binding partner of parkin. We also observed that
      parkin interacts and co-localizes with Dyrk1A in mammalian cells. In addition,
      Dyrk1A directly phosphorylated parkin at Ser-131, causing the inhibition of its
      E3 ubiquitin ligase activity. Moreover, Dyrk1A-mediated phosphorylation reduced
      the binding affinity of parkin to its ubiquitin-conjugating E2 enzyme and
      substrate, which could be the underlying inhibitory mechanism of parkin activity.
      Furthermore, Dyrk1A-mediated phosphorylation inhibited the neuroprotective action
      of parkin against 6-hydroxydopamine toxicity in dopaminergic SH-SY5Y cells. These
      findings suggest that Dyrk1A acts as a novel functional modulator of parkin.
      Parkin phosphorylation by Dyrk1A suppresses its E3 ubiquitin ligase activity
      potentially contributing to the pathogenesis of PD under PD-inducing pathological
      conditions. Mutations of parkin are linked to autosomal recessive forms of
      familial Parkinson's disease (PD). According to its functional relevance in
      abnormal protein aggregation and neuronal cell death, a number of post
      translational modifications regulate the ubiquitin E3 ligase activity of parkin.
      Here we propose a novel inhibitory mechanism of parkin E3 ubiquitin ligase
      through dual-specificity tyrosine-phosphorylation-regulated kinase 1A (Dyrk1A)
      mediated phosphorylation as well as its neuroprotective action against 6
      hydroxydopamine (6-OHDA)-induced cell death. The present work suggests that
      parkin phosphorylation by Dyrk1A may affect the pathogenesis of PD under PD
      inducing pathological conditions. 

PMID- 25963096
TI  - An Intrinsically Disordered Region in the Proapoptotic ASPP2 Protein Binds to the
      Helicobacter pylori Oncoprotein CagA.
AB  - The leading risk factor for gastric cancer in humans is infection by Helicobacter
      pylori strains that express and translocate the oncoprotein CagA into host
      epithelial cells. Once inside host cells, CagA interacts with ASPP2, which
      specifically stimulates p53-mediated apoptosis and reverses its pro-apoptotic
      function to promote ASPP2-dependent degradation of p53. The X-ray crystal
      structure of a complex between the N-terminal domain of CagA and a 56-residue
      fragment of ASPP2, of which 22 residues were resolved, was recently described.
      Here, we present biochemical and biophysical analyses of the interaction between
      the additional regions of CagA and ASPP2 potentially involved in this
      interaction. Using size exclusion chromatography-multiangle laser light
      scattering, circular dichroism, and nuclear magnetic resonance analyses, we
      observed that the ASPP2 region spanning residues 331-692, which was not part of
      the ASPP2 fragment used for crystallization, is intrinsically disordered in its
      unbound state. By surface plasmon resonance analysis and isothermal titration
      calorimetry, we found that a portion of this disordered region in ASPP2, residues
      448-692, binds to the N-terminal domain of CagA. We also measured the affinity of
      the complex between the ASPP2 fragment composed of residues 693-918 and inclusive
      of the fragment used for crystallization and CagA. Additionally, we mapped the
      binding regions between ASPP2 and CagA using peptide arrays, demonstrating
      interactions between CagA and numerous peptides distributed throughout the ASPP2
      protein sequence. Our results identify previously uncharacterized regions
      distributed throughout the protein sequence of ASPP2 as determinants of CagA
      binding, providing mechanistic insight into apoptosis reprogramming by CagA and
      potential new drug targets for H. pylori-mediated gastric cancer. 

PMID- 25963097
TI  - A physiological and biophysical model of coppice willow (Salix spp.) production
      yields for the contiguous USA in current and future climate scenarios.
AB  - High-performance computing has facilitated development of biomass production
      models that capture the key mechanisms underlying production at high spatial and
      temporal resolution. Direct responses to increasing [CO2 ] and temperature are
      important to long-lived emerging woody bioenergy crops. Fast-growing willow
      (Salix spp.) within short rotation coppice (SRC) has considerable potential as a
      renewable biomass source, but performance over wider environmental conditions and
      under climate change is uncertain. We extended the bioenergy crop modeling
      platform, BioCro, to SRC willow by adding coppicing and C3 photosynthesis
      subroutines, and modifying subroutines for perennation, allocation, morphology,
      phenology and development. Parameterization with measurements of leaf
      photosynthesis, allocation and phenology gave agreement of modeled with measured
      yield across 23 sites in Europe and North America. Predictions for the
      continental USA suggest yields of >=17 Mg ha(-1)  year(-1) in a 4 year rotation.
      Rising temperature decreased predicted yields, an effect partially ameliorated by
      rising [CO2 ]. This model, based on over 100 equations describing the
      physiological and biophysical mechanisms underlying production, provides a new
      framework for utilizing mechanism of plant responses to the environment,
      including future climates. As an open-source tool, it is made available here as a
      community resource for further application, improvement and adaptation.

PMID- 25963098
TI  - Reply to the "Comment on Vitamin D" by Kim et al. [Maturitas
      (doi:10.1016/j.maturitas.2015.03.008)].

PMID- 25963099
TI  - The exercise prescription for enhancing overall health of midlife and older
      women.
AB  - BACKGROUND: For midlife and older women, this period of their life is associated
      with an increase in risk factors for the development of chronic medical
      conditions. Data confirms the importance of regular exercise for both prevention
      and management of cardiovascular and other non-communicable diseases, unwanted
      weight gain, worsening metabolic profile and osteoporosis. However, in most
      clinical practices, midlife and older women patients are not offered specific
      exercise guidance. OBJECTIVES: This review assessed the current environment of
      what exercise advice is being offered to women at clinical encounters and
      suggests ways of incorporating an exercise prescription into clinical practice.
      MATERIALS AND METHODS: A PubMed review of the literature from the past 20 years
      was conducted. RESULTS: A universal template for an exercise prescription for
      aging women does not exist. Globally, there are scant programs that offer
      exercise advice and interventions to patients at the end of clinical encounters.
      CONCLUSIONS: Although most aging women know the benefits of engaging in a regular
      exercise program, many do not establish a regular routine. By the clinician
      offering an exercise prescription, this not only reinforces the importance of
      exercise but also provides simple guidelines on how women can commence an
      exercise routine in their life.

PMID- 25963100
TI  - Biomarkers for osteoarthritis: Can they be used for risk assessment? A systematic
      review.
AB  - The identification of early biochemical predictors of osteoarthritis (OA) has
      been the focus of much research over the past few years. However, it still is
      unclear whether current biochemical markers can be used in prognostic risk
      assessment of OA. The aim of this systematic review is to evaluate the possible
      prognostic application of blood and urinary biochemical markers of knee and hip
      OA. Abstract and full text selection was done by two independent reviewers. A
      total of 25 relevant publications including 37 biochemical markers of bone and
      cartilage turnover and inflammation associated with some aspects of OA were
      reviewed. Most of those biomarkers were studied only once or twice. Due to
      heterogeneity of both OA-phenotype and determinant among the publications, meta
      analysis of the studied biochemical markers was not possible. There was strong
      evidence for urinary C-terminal telopeptide of collagen type II (uCTX-II) as a
      prognostic marker for knee OA progression and serum cartilage oligomeric protein
      (COMP) level as prognostic marker for incidence of knee and hip OA. Evidence for
      prognostic value of C-reactive protein is still inconclusive. International
      standardization of future investigations should be pursued to obtain more high
      quality, homogenous data on the full spectrum of biochemical OA markers. 

PMID- 25963101
TI  - In Parkinson's disease pallidal deep brain stimulation speeds up response
      initiation but has no effect on reactive inhibition.
AB  - The fronto-striatal circuits are considered to mediate inhibitory control over
      action. The aim of this study was to investigate the contribution of the internal
      segment of the pallidum (GPi), one of the final output pathways from the basal
      ganglia to the cortex, in inhibition. We examined the effect of deep brain
      stimulation (DBS) of the GPi (GPi-DBS) in patients with Parkinson's disease who
      performed a conditional stop signal task, with DBS on and off. Modulation of GPi
      activity was associated with significantly faster Go reaction times with DBS on
      than off, but stop signal reaction times were not altered. Application of the
      drift diffusion model indicated that GPi-DBS was associated with significantly
      lower response thresholds compared to GPi-DBS off. However, the drift rate was
      significantly lower than healthy controls with both GPi-DBS on and off. These
      results suggest that the GPi plays a crucial role in the 'Go' pathway, perhaps
      facilitating reaching the required threshold to initiate actions. However, GPi
      DBS does not alter the functioning of the indirect 'NoGo' pathway, and other
      basal ganglia nuclei, such as the STN, may play a greater role in reactive
      response inhibition and conflict resolution. 

PMID- 25963103
TI  - A socio-sports model of disordered eating among Brazilian male athletes.
AB  - The objective of this study was to develop a socio-sports model of disordered
      eating (DE) in Brazilian male athletes. Three hundred and twenty one athletes
      over 12 years of age from 18 different sports modalities were investigated. The
      Eating Attitudes Test (EAT-26) was applied to evaluate DE. The Body Shape
      Questionnaire (BSQ) was used to evaluate athlete dissatisfaction with body fat
      levels. The Muscularity Concern subscale of the Drive for Muscularity Scale (DMS)
      was used to evaluate athlete dissatisfaction with muscularity levels. To
      investigate the influence of sociocultural factors on body image, the
      Sociocultural Attitudes Towards Appearance Questionnaire-3 (SATAQ-3) was applied.
      Body fat was estimated by skinfold measurement. Demographic data were collected
      (competitive level and training regimen). Structural equation modelling was
      conducted to analyse the relationships between research variables and the factors
      that mediate them. The results indicated that the sociocultural factors and body
      fat dissatisfaction adhered to socio-sports model of DE (X(2) = 18.50, p = .001,
      RMSEA = .069, GFI = .97, AGFI = .91, TLI = .93). The BSQ accurately predicted the
      relationship between SATAQ-3 and EAT-26 (R(2) = .08, p = 0.001) scores. A direct
      relationship between the SATAQ-3 and EAT-26 (R(2) = .07, p = 0.01) and BSQ (R(2)
      = .10, p = 0.001) scores was identified. No relationship was found between
      structural equation model and Muscularity Concern (R(2) = .02, p = 0.14),
      competitive level (R(2) = .01, p = 0.19), training regimen (R(2) = .03, p = 0.11)
      or body fat (R(2) = .02, p = 0.14). The results suggest that sociocultural
      factors and body fat dissatisfaction follow the socio-sports model of DE in
      Brazilian male athletes.

PMID- 25963102
TI  - Genotype status of the dopamine-related catechol-O-methyltransferase (COMT) gene
      corresponds with desirability of "unhealthy" foods.
AB  - The role of dopamine is extensively documented in weight regulation and food
      intake in both animal models and humans. Yet the role of dopamine has not been
      well studied in individual differences for food desirability. Genotype status of
      the dopamine-related catechol-O-methyltransferase (COMT) gene has been shown to
      influence dopamine levels, with greater COMT enzymatic activity in val/val
      individuals corresponding to greater degradation of dopamine. Decreased dopamine
      has been associated with poorer cognitive control and diminished goal-directed
      behavior in various behavioral paradigms. Additionally, dopaminergic-rich regions
      such as the frontal cortex and dorsal striatum have been shown to be important
      for supporting food-related decision-making. However, the role of dopamine, as
      assessed by COMT genotype status, in food desirability has not been fully
      explored. Therefore, we utilized an individual's COMT genotype status (n = 61)
      and investigated food desirability based on self-rated "healthy" and "unhealthy"
      food perceptions. Here we found val/val individuals (n = 19) have greater
      desirability for self-rated "unhealthy" food items, but not self-rated "healthy"
      food items, as compared to val/met (n = 24) and met/met (n = 18) individuals (p <
      0.005). Utilizing an objective health measure for the food items, we also found
      val/val and val/met individuals have greater desirability for objectively defined
      "unhealthy" food items, as compared to met/met individuals (p < 0.01). This work
      further substantiates the role of dopamine in food-related behaviors and more
      specifically in relationship to food desirability for "unhealthy" food items.

PMID- 25963104
TI  - Appetite, appetite hormone and energy intake responses to two consecutive days of
      aerobic exercise in healthy young men.
AB  - Single bouts of exercise do not cause compensatory changes in appetite, food
      intake or appetite regulatory hormones on the day that exercise is performed. It
      remains possible that such changes occur over an extended period or in response
      to a higher level of energy expenditure. This study sought to test this
      possibility by examining appetite, food intake and appetite regulatory hormones
      (acylated ghrelin, total peptide-YY, leptin and insulin) over two days, with
      acute bouts of exercise performed on each morning. Within a controlled laboratory
      setting, 15 healthy males completed two, 2-day long (09:00-16:00) experimental
      trials (exercise and control) in a randomised order. On the exercise trial
      participants performed 60 min of continuous moderate-high intensity treadmill
      running (day one: 70.1 +/- 2.5% VO2peak, day two: 70.0 +/- 3.2% VO2max (mean +/-
      SD)) at the beginning of days one and two. Across each day appetite perceptions
      were assessed using visual analogue scales and appetite regulatory hormones were
      measured from venous blood samples. Ad libitum energy and macronutrient intakes
      were determined from meals provided two and six hours into each day and from a
      snack bag provided in-between trial days. Exercise elicited a high level of
      energy expenditure (total = 7566 +/- 635 kJ across the two days) but did not
      produce compensatory changes in appetite or energy intake over two days (control:
      29,217 +/- 4006 kJ; exercise: 28,532 +/- 3899 kJ, P > 0.050). Two-way repeated
      measures ANOVA did not reveal any main effects for acylated ghrelin or leptin
      (all P > 0.050). However a significant main effect of trial (P = 0.029) for PYY
      indicated higher concentrations on the exercise vs. control trial. These findings
      suggest that across a two day period, high volume exercise does not stimulate
      compensatory appetite regulatory changes.

PMID- 25963105
TI  - Convenience, food and family lives. A socio-typological study of household food
      expenditures in 21st-century Belgium.
AB  - This article aims to uncover the extent to which convenience foods have become
      embedded in today's diets. The paper focuses on households' food expenditures,
      collected by Statistics Belgium in 2005. The results show that households'
      reliance on (semi-) convenience food items and away-from-home consumption clearly
      differs over the life-course and amongst different social groups. Findings show
      that single-living households (single men in particular) look for more
      convenience in their food preparation patterns compared to couples and households
      with children. The consumption of semi-convenient meal components seems to be
      more closely related to the conventional definition of home-cooking, with older
      generation, lower-educated, non-working and 'traditional' nuclear households
      being more likely to spend a larger share of their food budget on non-convenient
      and 'shortcut' ingredients. 

PMID- 25963106
TI  - The nutritional content and cost of supermarket ready-meals. Cross-sectional
      analysis.
AB  - BACKGROUND: Over-reliance on convenience foods, including ready-meals, has been
      suggested as one contributor to obesity. Little research has systematically
      explored the nutritional content of supermarket ready-meals. We described the
      nutritional content and cost of UK supermarket ready-meals. METHODS: We conducted
      a survey of supermarket own-brand chilled and frozen ready-meals available in
      branches of ten national supermarket chains in one city in northern England. Data
      on price, weight and nutritional content of meals in four ranges ('healthier',
      luxury, economy and standard) and of six types (macaroni cheese, meat lasagne,
      cottage pie, chicken tikka masala, fish pie, and sweet and sour chicken) were
      collected. Nutritional content was compared to ranges used to identify low,
      medium and high fat, saturated fat, sugar and salt in nationally recommended
      front-of-pack labelling. RESULTS: 166 ready-meals were included from 41 stores.
      Overall, ready-meals were high in saturated fat and salt, and low in sugar. One
      fifth of meals were low in fat, saturated fat, salt and sugar, including two
      thirds of 'healthier' meals. Meals that were low for three out of the four front
      of-pack nutrients were the cheapest. CONCLUSIONS: Supermarket ready-meals do not
      have a healthful nutritional profile overall. However, a number of healthier
      meals were available - particularly amongst meals specifically marked as
      'healthier'. There was little evidence that healthier meals necessarily cost
      more. Further effort is required to encourage producers to improve the
      nutritional profile of the full range of ready-meals, and not just those
      specifically labelled as 'healthier'.

PMID- 25963107
TI  - Habitual total water intake and dimensions of mood in healthy young women.
AB  - Acute negative and positive mood states have been linked with the development of
      undesirable and desirable health outcomes, respectively. Numerous factors acutely
      influence mood state, including exercise, caffeine ingestion, and macronutrient
      intake, but the influence of habitual total water intake remains unknown. The
      purpose of this study was to observe relationships between habitual water intake
      and mood. One hundred twenty healthy females (mean +/- SD; age = 20 +/- 2 y, BMI
      = 22.9 +/- 3.5 kg?m(-2) ) recorded all food and fluids consumed for 5 consecutive
      days. Investigators utilized dietary analysis software to determine Total Water
      Intake (TWI; total water content in foods and fluids), caffeine, and
      macronutrient consumption (i.e. protein, carbohydrate, fat). On days 3 and 4,
      participants completed the Profile of Mood State (POMS) questionnaire, which
      examined tension, depression, anger, vigor, and confusion, plus an aggregate
      measure of Total Mood Disturbance (TMD). For comparison of mood, data were
      separated into three even groups (n = 40 each) based on TWI: low (LOW; 1.51 +/-
      0.27 L/d), moderate (MOD; 2.25 +/- 0.19 L/d), and high (HIGH; 3.13 +/- 0.54 L/d).
      Regression analysis was performed to determine continuous relationships between
      measured variables. Group differences (p < 0.05) were observed for tension (MOD =
      7.2 +/- 5.4, HIGH = 4.4 +/- 2.9), depression (LOW = 4.5 +/- 5.9, HIGH = 1.7 +/-
      2.3), confusion (MOD = 5.9 +/- 3.4, HIGH = 4.0 +/- 2.1), and TMD (LOW=19.0 +/-
      21.8, HIGH=8.2 +/- 14.2). After accounting for other mood influencers, TWI
      predicted TMD (r(2) = 0.104; p = 0.050). The above relationships suggest the
      amount of water a woman consumes is associated with mood state.

PMID- 25963108
TI  - Low-level mosaicism of a de novo derivative chromosome 9 from a
      t(5;9)(q35.1;q34.3) has a major phenotypic impact.
AB  - Microdeletion and microduplication syndromes are well-known causes of
      developmental delay and/or malformations of differing severity. Although
      homogeneous abnormalities can now be detected relatively easily using microarray
      technologies, they are more difficult to detect and interpret in cases of
      mosaicism. Here, we report on a male infant with a mosaic de novo derivative
      chromosome 9, featuring a 10.2 Mb 5q35 duplication (including the NSD1 gene) and
      a 687 kb 9q34 deletion (including EHMT1). The infant presented developmental
      delay, short stature, brachy/plagiocephaly and hyperactivity. The proportion of
      abnormal cells was 50% in saliva (in a microarray analysis) and 25% in
      lymphocytes (in a FISH analysis). Despite the low-level mosaicism in lymphocytes,
      this imbalance appears to be responsible for a distinctive phenotype (suggesting
      the presence of variable clinical expression and/or major somatic mosaicism). 

PMID- 25963109
TI  - Psychosocial staffing at National Comprehensive Cancer Network member
      institutions: data from leading cancer centers.
AB  - OBJECTIVE: The National Comprehensive Cancer Network (NCCN) is comprised of 25
      National Cancer Institute-designated cancer centers and arguably could thus set
      the standard for optimal psychosocial staffing for cancer centers; therefore,
      information was sought from NCCN Member Institutions about their current staffing
      for psychosocial services. These findings are put into perspective given the
      limited existing literature and consensus reports. METHODS: The NCCN Best
      Practices Committee surveyed member institutions about their staffing for
      psychosocial services. The survey was administered electronically in the winter
      of 2012. RESULTS: The survey was completed by 20 cancer centers. Across
      institutions, case managers and mental health therapists, typically social
      workers, were utilized most frequently to provide psychosocial services (67% of
      full-time-equivalents (FTEs)), with other psychosocial professionals also
      represented but less consistently. Most psychosocial services are institutionally
      funded (ranging from 64 to 100%), although additional sources of support include
      fee for service and grant funding. Training of psychosocial providers is unevenly
      distributed across responding sites, ranging from 92% of institutions having
      training programs for psychiatrists to 36% having training programs for mental
      health therapists. CONCLUSIONS: There was variability among the institutions in
      terms of patient volume, psychosocial services provided, and psychosocial staff
      employed. As accreditation standards are implemented that provide impetus for
      psychosocial services in oncology, it is hoped that greater clarity will develop
      concerning staffing for psychosocial services and uptake of these services by
      patients with cancer.

PMID- 25963110
TI  - Planning for the health workforce is essential.

PMID- 25963111
TI  - Spectacle-related eye injuries, spectacle-impact performance and eye protection.
AB  - The aim was to review the prevalence of spectacle-related ocular trauma and the
      performance of currently available spectacle materials and to identify the risk
      factors associated with spectacle-related ocular trauma. A literature review was
      conducted using Medline, Embase and Google with the keywords 'eyeglasses' OR
      'spectacles' AND 'ocular injury' / 'eye injury'/ 'eye trauma' / 'ocular trauma'.
      Articles published prior to 1975 were excluded from this review because of
      advances in spectacle lens technology and Food and Drug Administration
      legislative changes requiring impact resistance of all prescription spectacle
      lenses in the United States. Six hundred and ninety-five individual ocular
      traumas, for which spectacles contributed to or were the main cause of injury,
      were identified in the literature. Eye injuries occurred when spectacles were
      worn in sports, in which medium- to high-impact energies were exerted from balls,
      racquets or bats and/or as a result of a collision with another player. Frame,
      lens design and product material choice were found to be associated with ocular
      injury, with polycarbonate lenses cited as the material of choice in the
      literature. International, regional and national standards for spectacle lenses
      had a wide range of impact requirements for prescription spectacle lenses, sports
      eye protection and occupational eye protection. Spectacle-related injury
      represents a small but preventable cause of ocular injury. With the increasing
      numbers of spectacle wearers and calls to spend more time outdoors to reduce
      myopia, spectacle wearers need to be made aware of the potential risks associated
      with wearing spectacles during medium- to high-risk activities. At particular
      risk are those prone to falls, the functionally one-eyed, those who have corneal
      thinning or have had previous eye surgery or injury. With increased understanding
      of specific risk factors, performance guidelines can be developed for
      prescription spectacle eye-protection requirements.

PMID- 25963112
TI  - Exponential prevalence and incidence equations for myopia.
AB  - BACKGROUND: This project relates prevalence-time data, incidence rate data, age
      of onset, system plateau level and system time constant, using exponential
      equations, as they apply to progressive myopia, useful over several decades.
      METHODS: Cross-sectional refractive data is analysed for nine studies with a
      total number of subjects at 444.6 K (345, 981, 7.6 K, 39, 421 K, 383, 2 K, 12 K,
      255), with ages ranging from five to 39 years. Basic exponential equations allow
      calculation of the prevalence versus time function Pr(t) as a percentage and the
      incidence rate function In(t) (percentage per year), system time constant t0
      (years), onset age t1 (years) and saturation plateau level <S> (percentage).
      RESULTS: The prevalence of myopia as a function of time Pr(t) (years) and
      incidence of myopia as a function of time In(t) (percentage per year) are
      continuously generated and compared with prevalence/incidence data from various
      reports investigating student populations. For a general medical condition,
      typical values for time constant t0 may range from one week to five years,
      depending on the health condition. Typical plateau levels for myopia may range
      from 35 to 95 per cent. Herein, data from nine demographic studies of myopia are
      analysed for prevalence Pr(t) with an accuracy within 14 per cent and incidence
      In(t) within 2.6 per cent per year, onset t1 = 1.5 years, time constant t0 = 4.5
      year. By comparison, linear regression can predict the prevalence of myopia Pr(t)
      within 11 per cent and estimates a constant incidence rate for myopia In(t) of
      4.7 per cent per year (95 per cent CI: 2.1 to 7.3 per cent per year].
      CONCLUSIONS: The initial incidence rate at onset age In(t1) and system time
      constant t0 are inversely related. For myopia, onset age, time constant and
      saturation plateau level are fundamental system parameters derived from age
      specific prevalence and incidence data.

PMID- 25963113
TI  - Computer vision syndrome in presbyopia and beginning presbyopia: effects of
      spectacle lens type.
AB  - PURPOSE: This office field study investigated the effects of different types of
      spectacle lenses habitually worn by computer users with presbyopia and in the
      beginning stages of presbyopia. Computer vision syndrome was assessed through
      reported complaints and ergonomic conditions. METHODS: A questionnaire regarding
      the type of habitually worn near-vision lenses at the workplace, visual
      conditions and the levels of different types of complaints was administered to
      175 participants aged 35 years and older (mean +/- SD: 52.0 +/- 6.7 years).
      Statistical factor analysis identified five specific aspects of the complaints.
      Workplace conditions were analysed based on photographs taken in typical working
      conditions. RESULTS: In the subgroup of 25 users between the ages of 36 and 57
      years (mean 44 +/- 5 years), who wore distance-vision lenses and performed more
      demanding occupational tasks, the reported extents of 'ocular strain',
      'musculoskeletal strain' and 'headache' increased with the daily duration of
      computer work and explained up to 44 per cent of the variance (rs = 0.66). In the
      other subgroups, this effect was smaller, while in the complete sample (n = 175),
      this correlation was approximately rs = 0.2. The subgroup of 85 general-purpose
      progressive lens users (mean age 54 years) adopted head inclinations that were
      approximately seven degrees more elevated than those of the subgroups with single
      vision lenses. CONCLUSIONS: The present questionnaire was able to assess the
      complaints of computer users depending on the type of spectacle lenses worn. A
      missing near-vision addition among participants in the early stages of presbyopia
      was identified as a risk factor for complaints among those with longer daily
      durations of demanding computer work.

PMID- 25963114
TI  - Comparison of progressive addition lenses for general purpose and for computer
      vision: an office field study.
AB  - BACKGROUND: Two types of progressive addition lenses (PALs) were compared in an
      office field study: 1. General purpose PALs with continuous clear vision between
      infinity and near reading distances and 2. Computer vision PALs with a wider zone
      of clear vision at the monitor and in near vision but no clear distance vision.
      METHODS: Twenty-three presbyopic participants wore each type of lens for two
      weeks in a double-masked four-week quasi-experimental procedure that included an
      adaptation phase (Weeks 1 and 2) and a test phase (Weeks 3 and 4). Questionnaires
      on visual and musculoskeletal conditions as well as preferences regarding the
      type of lenses were administered. After eight more weeks of free use of the
      spectacles, the preferences were assessed again. The ergonomic conditions were
      analysed from photographs. RESULTS: Head inclination when looking at the monitor
      was significantly lower by 2.3 degrees with the computer vision PALs than with
      the general purpose PALs. Vision at the monitor was judged significantly better
      with computer PALs, while distance vision was judged better with general purpose
      PALs; however, the reported advantage of computer vision PALs differed in extent
      between participants. Accordingly, 61 per cent of the participants preferred the
      computer vision PALs, when asked without information about lens design. After
      full information about lens characteristics and additional eight weeks of free
      spectacle use, 44 per cent preferred the computer vision PALs. CONCLUSION: On
      average, computer vision PALs were rated significantly better with respect to
      vision at the monitor during the experimental part of the study. In the final
      forced-choice ratings, approximately half of the participants preferred either
      the computer vision PAL or the general purpose PAL. Individual factors seem to
      play a role in this preference and in the rated advantage of computer vision
      PALs.

PMID- 25963115
TI  - How to place the computer monitor: measurements of vertical zones of clear vision
      with presbyopic corrections.
AB  - BACKGROUND: This study intended to measure the near and far points of clear
      vision as a function of the inclination of the line of sight with comfortable
      head posture. Measurements with different lenses for presbyopic correction were
      made to suggest comfortable positions of the monitor for computer work. METHOD:
      An 'inclined optometer' was built, including a concave mirror to shift a visual
      target of constant angular size from near to infinity (proposed by Reiner). The
      optometer could be inclined vertically from horizontal to 50 degrees downward to
      vary the inclination of the line of sight. Measurements were made with a
      comfortable head position adjusted on a headrest. RESULTS: The near and far
      points were plotted both in the unit one/metre as a function of eye inclination
      (optometric diagram) and also as positions from the eyes in workspace co
      ordinates (workplace diagram). First, individual examples of plots of the
      vertical zones of clear vision at the workplace are shown. Second, the group mean
      data of 22 observers with newly prescribed lenses showed that the vertical zones
      of clear vision for general purpose progressive addition lenses (PALs) reach
      infinity and are flatter, while computer vision PALs lead to more steep vertical
      zones ending at intermediate distances. Third, the mean results of three samples
      from our laboratory were compared with respect to general purpose PALs, which are
      most frequently used by presbyopic people. CONCLUSIONS: The diagrams of the
      vertical zones of clear vision for different spectacles provide information on
      the ergonomic vertical position of computer monitors for clear vision with a
      comfortable head position. The grand mean of general purpose PALs suggests that
      the upper edge of the monitor should be at least approximately 15 cm below eye
      level at a typical viewing distance of approximately 75 cm. Higher monitor
      positions are possible with computer vision PALs.

PMID- 25963116
TI  - Optometric supply and demand in Australia: 2011-2036.
AB  - BACKGROUND: The effective size of the optometric workforce is dependent on
      graduate numbers, retention rates and immigration and is influenced by age,
      gender and working hours of optometrists. This paper presents modelling results
      of the relationship between the projected Australian optometric workforce and
      projected demand for optometric services for the period 2011 to 2036. Nine
      hypothetical optometric supply-side and demand-side scenarios are presented.
      METHODS: Data from the Australian Bureau of Statistics on age and gender of
      people listing optometry as their major qualification in the 2011 census were
      projected over a 25-year period, accounting for factors such as concordance with
      Health Workforce Australia figures for registered optometrists in Australia in
      2011, ageing, attrition, hours worked, new graduates and immigration. Data were
      compared to the numbers of optometrists calculated as necessary to meet the
      demand for services of the Australian population to 2036 using nine different
      scenarios. RESULTS: It was estimated that there would be a surplus of over 1,200
      equivalent full-time optometrists (EFTO) in 2036 for the highest service demand
      scenario of 13.8 million Medicare services, where 21 hours of a 38-hour week per
      EFTO were allowed for the provision of optometric services under Medicare.
      Substantial surpluses were predicted in all states and territories except
      Queensland, Tasmania and the Northern Territory where predicted supply was within
      six EFTO of predicted demand. CONCLUSIONS: Projections using current weightings
      for mortality, attrition, proportion of optometrists in active practice, working
      hours, immigration, new graduates and 21 hours per EFTO per week available for
      Medicare services indicate that in 2036, there will be excess optometrists in
      relation to projected demand for services, if service utilisation is maintained
      at current levels or increased by 10 or 20 per cent. Substantially greater
      excesses result if each EFTO has 28 or 35 hours per week available for Medicare
      services.

PMID- 25963118
TI  - New insights into the origin of the lumbrical muscles of the foot: tendinous slip
      of the flexor hallucis longus muscle.
AB  - PURPOSE: The aim of this study was to clarify the origins of the lumbricals of
      the foot toward a better understanding of its precise action in the gait.
      METHODS: The lumbricals in the foot were investigated in 66 specimens of embalmed
      Korean adult cadavers. RESULTS: The first lumbrical arose as two muscle bellies
      from both the tendon of the FDL and the tendinous slip of the FHL in 83.3 %, and
      as one muscle belly from the tendon of the FDL or the tendinous slip of the FHL
      in 16.7 %. These two muscle bellies subsequently merged to form the muscle belly
      of the first lumbrical. The second lumbrical arose from the tendinous slips of
      the FHL for the second and third toes as well as the tendon of the FDL in all
      specimens. The third lumbrical arose from the tendinous slips of the FHL for the
      third and fourth toes in 69.7 %, and the fourth lumbrical arose from the
      tendinous slip of the FHL for the fourth toe in 18.2 %. Some deep muscle fibers
      of the fourth lumbrical arose from the tendinous slip of the FHL for the second
      toe in 4.5 %, for the third toe in 28.8 %, and for the fourth toe in 15.2 %.
      CONCLUSIONS: The results of this study constitute new anatomical knowledge
      regarding the origin of the lumbricals, and provide insight into their specific
      role in production of gait. These findings will be useful for various types of
      surgery, biomechanics research, and rehabilitation programs.

PMID- 25963119
TI  - The association between petrous apex cephalocele and empty sella.
AB  - PURPOSE: Petrous apex cephalocele (PAC) is a rare lesion that has been linked to
      empty sella in several case reports. The aim of this study is to document the
      incidence of empty sella and PAC in consecutive brain MRI studies and study the
      association between these two lesions to better understand the underlying
      etiology of PAC. METHODS: A total of 2410 brain MRI studies were performed in our
      institution in the period from January 2011 to December 2011. After eliminating
      duplicated studies, a total of 2093 studies met our inclusion criteria.
      Retrospective analysis of patients' head MRI was performed by two radiologists
      independently to identify the presence of empty sella and/or PAC. RESULTS: Empty
      sella was found in 322 (15.4 %) patients. PAC was found in 111 (5.3 %) patients
      (age range 6-81 years) of which 87 were females and 24 were males. Of all the
      patients with PAC, 77 (69.4 %) patients had associated empty sella. Bilateral PAC
      was more common and seen in 77 patients. CONCLUSION: PAC is associated with empty
      sella, and both lesions are probably related to the same cause.

PMID- 25963120
TI  - Factors influencing mental health nurses' attitudes towards people with mental
      illness.
AB  - This study aimed to investigate the factors influencing mental health nurses'
      attitudes towards people with mental illness. A descriptive correlation design
      was used. A sample of 180 Taiwanese mental health nurses was recruited from
      mental health-care settings. Data were analyzed with descriptive statistics,
      Pearson's product-moment correlation, Student's t-test, one-way anova, and a
      hierarchical multiple regression analysis. Negative attitudes were found among
      mental health nurses, especially with respect to individuals with substance abuse
      compared with those with schizophrenia and major depression. Mental health nurses
      who were older, had more clinical experiences in mental health care, and
      demonstrated greater empathy expressed more positive attitudes towards people
      with mental illness. Mental health nurses working at acute psychiatric units
      demonstrated more negative attitudes towards mental illness compared with those
      working in psychiatric rehabilitation units and outpatient clinics or community
      psychiatric rehabilitation centres. Particularly, length of mental health nursing
      practice and empathy significantly accounted for mental health nurses' attitudes
      towards mental illness. Understanding nurses' attitudes and their correlates
      towards people with mental illness is critical to deliver effective mental health
      nursing care. 

PMID- 25963121
TI  - Assessment of tandem mass spectrometry and high-resolution mass spectrometry for
      the analysis of bupivacaine in plasma.
AB  - Triple quadrupole mass spectrometers coupled with high performance liquid
      chromatography are workhorses in quantitative bioanalyses. They provide
      substantial benefits including reproducibility, sensitivity and selectivity for
      trace analysis. Selected reaction monitoring allows targeted assay development
      but datasets generated contain very limited information. Data mining and analysis
      of nontargeted high-resolution mass spectrometry profiles of biological samples
      offer the opportunity to perform more exhaustive assessments, including
      quantitative and qualitative analysis. The objectives of this study were to test
      method precision and accuracy, to statistically compare bupivacaine drug
      concentration in real study samples and to verify if high-resolution and accurate
      mass data collected in scan mode can actually permit retrospective data analysis,
      more specifically, extract metabolite related information. The precision and
      accuracy data presented using both instruments provided equivalent results.
      Overall, the accuracy ranged from 106.2 to 113.2% and the precision observed was
      from 1.0 to 3.7%. Statistical comparisons using a linear regression between both
      methods revealed a coefficient of determination (R(2)) of 0.9996 and a slope of
      1.02, demonstrating a very strong correlation between the two methods. Individual
      sample comparison showed differences from -4.5 to 1.6%, well within the accepted
      analytical error. Moreover, post-acquisition extracted ion chromatograms at m/z
      233.1648 +/- 5 ppm (M - 56) and m/z 305.2224 +/- 5 ppm (M + 16) revealed the
      presence of desbutyl-bupivacaine and three distinct hydroxylated bupivacaine
      metabolites. Post-acquisition analysis allowed us to produce semi-quantitative
      evaluations of the concentration-time profiles for bupicavaine metabolites.

PMID- 25963122
TI  - Mycophenolate mofetil may induce prolonged severe anemia during pegylated
      interferon/ribavirin/simeprevir therapy in liver transplant recipients.
AB  - Aim: Pegylated-interferon/ribavirin/simeprevir (PEG-IFN/RBV/SMV) combination
      therapy is widely used for hepatitis C virus (HCV) treatment after liver
      transplantation (LT). Here, we observed two cases of extended severe anemia
      during PEG-IFN/RBV/SMV therapy for HCV serological type 1 re-infected after LT.
      Immunosuppressants consisted of tacrolimus and mycophenolate mofetil (MMF). Case
      1 was a 65-year-old-woman treated with PEG-IFN/RBV/SMV therapy and 500 mg MMF/day
      9 months after LT. Her serum hemoglobin (Hb) level decreased from 10 to 8.4 mg/dL
      on day 25. Despite discontinuing the PEG-IFN/RBV/SMV treatment on day 32, her Hb
      level decreased to 5.1 mg/dL on day 40. Case 2 was a 61-year-old-woman started on
      PEG-IFN/RBV/SMV therapy 20 months after LT. Her serum Hb level decreased from
      12.2 to 7.1 mg/dL on day 39. The MMF dose was reduced from 1,500 to 1,000 mg/day,
      and her Hb level was maintained. Red blood cell transfusions were required in
      both cases, and anemia persisted for 2 months. These patients had the C/C major
      type inosine triphosphatase (ITPA) polymorphism. In conclusion, MMF induced
      severe persistent anemia by co-treatment with IFN/RBV in patients who underwent
      LT. Thus, the immunosuppressant dose should be chosen carefully for patients with
      the high-risk ITPA allele.

PMID- 25963123
TI  - Dietary n-3 polyunsaturated fatty acids revert renal responses induced by a
      combination of 2 protocols that increase the amounts of advanced glycation end
      product in rats.
AB  - Renal dysfunction is a severe complication that is caused by diabetes mellitus.
      Many factors associate the progression of this complication with high levels of
      proinflammatory and pro-oxidant substances, such as advanced glycation end
      products (AGEs), which form a heterogeneous group of compounds that can
      accumulate in tissues such as retinas, joints, and kidneys. The hypothesis of
      this study is that n-3 polyunsaturated fatty acids (n-3 PUFAs) have a
      nephroprotective effect on rats after exposing them to a combination of 2
      protocols that increase the AGE amounts: a high-fat diet enriched with AGEs and a
      diabetes rat model. Adult Wistar rats were divided into 6 groups that received
      the following diets for 4 weeks: (1) control group; 2) HAGE: high AGE fat
      containing diet group; (3) HAGE + n-3: high AGE fat-containing diet plus n-3
      PUFAs group; (4) diabetic group; (5) Db + HAGE: high AGE fat-containing diet
      diabetic group; and (6) Db + HAGE + n-3: high AGE fat-containing diet plus n-3
      PUFAs diabetic group. Diabetes mellitus was induced by an intraperitoneal
      injection of alloxan (150 mg kg(-1)). In diabetic and nondiabetic rats, the high
      HAGE fat-containing diet increased the serum creatinine, tumor necrosis factor
      alpha, thiobarbituric acid reactive substances, and reactive oxygen species
      levels, as well as the superoxide dismutase/catalase + glutathione peroxidase
      ratio and the superoxide dismutase 2 and receptor for advanced glycation end
      products immunocontent of the kidneys. n-3 Polyunsaturated fatty acids attenuated
      these alterations and influenced the receptor for advanced glycation end
      products/oxidative stress/tumor necrosis factor-alpha axis. In summary, this
      study showed that the extrinsic AGE pathway (HAGE diet) had a greater effect on
      renal metabolism than the intrinsic AGE pathway (diabetes induction) and that n-3
      PUFAs appear to prevent renal dysfunction via antioxidant and anti-inflammatory
      pathways. 

PMID- 25963124
TI  - Genomic characterization of two novel polyomaviruses in Brazilian insectivorous
      bats.
AB  - Two novel genomes comprising ~4.9 kb were identified by next-generation
      sequencing from pooled organs of Tadarida brasiliensis bats. The overall
      nucleotide sequence identities between the viral genomes characterized here were
      less than 80% in comparison to other polyomaviruses (PyVs), members of the family
      Polyomaviridae. The new genomes display the archetypal organization of PyVs,
      which includes open reading frames for the regulatory proteins small T antigen
      (STAg) and large T antigen (LTAg), as well as capsid proteins VP1, VP2 and VP3.
      In addition, an alternate ORF was identified in the early genome region that is
      conserved in a large monophyletic group of polyomaviruses. Phylogenetic analysis
      showed similar clustering with group of PyVs detected in Otomops and Chaerephon
      bats and some species of monkeys. In this study, the genomes of two novel PyVs
      were detected in bats of a single species, demonstrating that these mammals can
      harbor genetically diverse polyomaviruses.

PMID- 25963126
TI  - Prevalence and risk factors of sexual dysfunction in postpartum Australian women.
AB  - INTRODUCTION: Female sexual dysfunction is highly prevalent and reportedly has
      adverse impacts on quality of life. Although it is prevalent after childbirth,
      women rarely seek advice or treatment from health care professionals. AIM: The
      aim of this study was to assess the sexual functioning of Australian women during
      the first year after childbirth. METHODS: Postpartum women who had given birth
      during the previous 12 months were invited to participate in this cross-sectional
      study. A multidimensional online questionnaire was designed for this study. This
      questionnaire included a background section, the Female Sexual Function Index,
      the Patient Health Questionnaire (PHQ-8), and the Relationship Assessment Scale.
      Responses from 325 women were analyzed. RESULTS: Almost two-thirds of women
      (64.3%) reported that they had experienced sexual dysfunction during the first
      year after childbirth, and almost three-quarters reported they experienced sexual
      dissatisfaction (70.5 %). The most prevalent types of sexual dysfunction reported
      by the affected women were sexual desire disorder (81.2%), orgasmic problems
      (53.5%), and sexual arousal disorder (52.3%). The following were significant risk
      factors for sexual dysfunction: fortnightly or less frequent sexual activity, not
      being the initiator of sexual activity with a partner, late resumption of
      postnatal sexual activity (at 9 or more weeks), the first 5 months after
      childbirth, primiparity, depression, and relationship dissatisfaction.
      CONCLUSION: Sexual satisfaction is important for maintaining quality of life for
      postpartum women. Health care providers and postpartum women need to be
      encouraged to include sexual problems in their discussions.

PMID- 25963127
TI  - Establishment of a novel orthotopic model of breast cancer metastasis to the
      lung.
AB  - Breast cancer is the second leading cause of cancer-related death among women,
      and distant metastasis is responsible for the death of ~90% of these patients.
      However, despite recent advances, the underlying mechanisms responsible for
      breast cancer metastasis remain elusive. A great impediment to this is the lack
      of appropriate orthotopic models of breast cancer metastasis to distant organs.
      In the present study, we established a novel orthotopic model of breast cancer
      metastasis to the lungs in mice, where metastatic sublines of 4T1 cells revealed
      enhanced metastatic propensity to the lungs. All mice (100%) developed lung
      metastasis upon orthotopic implantation of a metastatic subline of 4T1 cells, in
      contrast to 10% of mice with lung metastasis for a subline derived from primary
      tumors and 60% of mice with lung metastasis for parental 4T1 cells. At the
      molecular level, significant epithelial-mesenchymal transition was characterized
      in these metastatic sublines, which is likely at least partially, responsible for
      the enhanced metastasis. These established cell lines provide a novel platform to
      study the relevant molecular basis of metastasis and metastasis-specific
      therapeutics.

PMID- 25963128
TI  - Altered secretion of selected arachidonic acid metabolites during subclinical
      endometritis relative to estrous cycle stage and grade of fibrosis in mares.
AB  - Mares that fail to become pregnant after repeated breeding, without showing
      typical signs of clinical endometritis, should be suspected of subclinical
      endometritis (SE). Contact with infectious agents results in altered synthesis
      and secretion of inflammatory mediators, including cytokines and arachidonic acid
      metabolites, and disturbs endometrial functional balance. To address the
      hypothesis that SE affects the immune endocrine status of the equine endometrium,
      spontaneous secretion of prostaglandin E(2) (PGE(2)), prostaglandin F(2alpha)
      (PGF(2alpha)), 6-keto-PGF(1alpha )(a metabolite of prostacyclin I(2)),
      leukotriene B(4) (LTB(4)), and leukotriene C(4) (LTC(4)) was examined. In
      addition, secretion of these factors was examined relative to the grade of
      inflammation, fibrosis, and estrous cycle stage. Eighty-two warmblood mares, of
      known breeding history, were enrolled in this study. On the basis of
      histopathologic assessment, mares were classified as suffering from first-grade
      SE, second-grade SE, or being healthy. The grade of fibrosis and the infiltration
      of endometrial tissue with polymorphonuclear leukocytes were examined by routine
      hematoxylin-eosin staining. In mares suffering from SE, the secretion profiles of
      PGE(2), 6-keto-PGF(1alpha), LTB(4), and LTC(4) were changed compared to mares
      that did not suffer from endometritis. The secretion of PGE(2) and 6-keto
      PGF1alpha was increased, whereas that of LTB(4) and LTC(4) was decreased.
      Secretion of 6-keto-PGF(1alpha) was increased in first- and second-grade SE (P <
      0.01). The concentration of PGI(2) metabolite was increased only in inflamed
      endometrium, independently of the inflammation grade, but was not affected by
      fibrosis. Prostaglandin E(2) secretion was increased in second-grade SE (P <
      0.05). The secretion of LTB(4) decreased in both first- and second-grade SE (P <
      0.05), whereas secretion of LTC(4) was decreased only in second-grade SE (P <
      0.05). Fibrosis did not change the secretion profile of PGE(2), PGF(2alpha), and
      6-keto-PGF(1alpha) during the course of SE. However, the secretion profile of
      LTB(4) was affected during the course of fibrosis. Evident divergences between
      PGE(2) and PGF(2alpha) profiles and in PGE2:PGF(2alpha) ratios in the control
      versus SE mares observed during the course of diestrus contribute to shortened or
      prolonged interestrous intervals observed clinically in SE mares.

PMID- 25963129
TI  - Double ovulation and occurrence of twinning in alpacas (Vicugna pacos).
AB  - Twin births are rare in alpacas despite the high incidence of double ovulation
      and are undesirable because they contribute to early and late pregnancy loss,
      abortion, and birth of nonviable neonates. The objective of the present study was
      to determine the incidence and outcome of twin pregnancy in double-ovulating
      alpacas by retrospective and prospective analysis. Data from double-ovulating
      females (N = 41) presented for pregnancy diagnosis were analyzed to determine
      pregnancy status at three stages after mating (14-16, 25-30, and 45-53 days). In
      a prospective study, adult reproductively sound alpacas (n = 21) were examined by
      ultrasonography to determine the incidence of multiple ovulations. A subset of
      those alpacas (n = 10) were euthanized either at 9 days (n = 5) or 14 days (n =
      5) after a single mating and administration of GnRH to determine presence and
      number of embryos. A total of 31 cycles were included in the study to determine
      the incidence of multiple ovulations. In the retrospective study, twin
      pregnancies were identified between 25 and 30 days in 47.1% of double-ovulating
      females. There were more twins from bilateral ovulations (62.5%) than from
      unilateral ovulations (37.5%). Twin pregnancies were either reduced to a
      singleton (62.5%) or lost completely (37.5%). One set of twins remained viable
      until Day 52. In the prospective study, double ovulation occurred in 18.8% of the
      cycles. Two embryos were collected from two of the four double-ovulating females.
      In conclusion, twin conception is not rare in alpacas. A high rate of spontaneous
      reduction of twin pregnancies occurs before Day 45. However, a significant
      proportion of twin pregnancy may result in loss of both embryos. Determination of
      the number of ovulations (CL) at the time of early pregnancy diagnosis (14-16
      days) should be an integral part of any pregnancy evaluation.

PMID- 25963125
TI  - Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human
      cancer cells.
AB  - Mitochondrial genomes are separated from the nuclear genome for most of the cell
      cycle by the nuclear double membrane, intervening cytoplasm, and the
      mitochondrial double membrane. Despite these physical barriers, we show that
      somatically acquired mitochondrial-nuclear genome fusion sequences are present in
      cancer cells. Most occur in conjunction with intranuclear genomic rearrangements,
      and the features of the fusion fragments indicate that nonhomologous end joining
      and/or replication-dependent DNA double-strand break repair are the dominant
      mechanisms involved. Remarkably, mitochondrial-nuclear genome fusions occur at a
      similar rate per base pair of DNA as interchromosomal nuclear rearrangements,
      indicating the presence of a high frequency of contact between mitochondrial and
      nuclear DNA in some somatic cells. Transmission of mitochondrial DNA to the
      nuclear genome occurs in neoplastically transformed cells, but we do not exclude
      the possibility that some mitochondrial-nuclear DNA fusions observed in cancer
      occurred years earlier in normal somatic cells.

PMID- 25963130
TI  - DNA integrity of canine spermatozoa during chill storage assessed by the sperm
      chromatin dispersion test using bright-field or fluorescence microscopy.
AB  - The objective of this study was to evaluate the effect of chill storage on canine
      sperm DNA fragmentation assessed by the sperm chromatin dispersion test using
      bright-field microscopy with Wright solution (sDF-B) or fluorescence microscopy
      with propidium iodide (sDF-F). The relationship and agreement between the results
      obtained with both staining methods were analyzed. The values of DNA
      fragmentation indexes (sDF-F and sDF-B) were compared at each time of chill
      storage (0, 24, 48, 72, and 96 hours). Additionally, the sperm DNA fragmentation
      rate (slope) was compared between the methods during chill storage. Good
      agreement and no significant differences between values obtained with both
      staining procedures were observed. Finally, the effect of chill storage for up to
      96 hours was assessed on sperm motility parameters and DNA fragmentation indexes.
      Significant differences were found after 48 hours of chill storage, obtaining
      greater values of fragmented DNA. Progressive sperm motility was lower just after
      96 hours of chill storage, and no effect was found in total sperm motility. In
      conclusion, the Sperm-Halomax kit, developed for canine semen and based on the
      sperm chromatin dispersion test, can be used accurately under bright-field or
      fluorescence microscopy to assess the sperm DNA integrity of canine semen during
      chill storage. The sperm DNA fragmentation index increased after 48 hours of
      chill storage, thereby detecting sperm damage earlier than other routine sperm
      parameters, such as sperm motility.

PMID- 25963131
TI  - Body mass index and outcome in renal transplant recipients: a systematic review
      and meta-analysis.
AB  - BACKGROUND: Whether overweight or obese end stage renal disease (ESRD) patients
      are suitable for renal transplantation (RT) is often debated. The objective of
      this review and meta-analysis was to systematically investigate the outcome of
      low versus high BMI recipients after RT. METHODS: Comprehensive searches were
      conducted in MEDLINE OvidSP, Web of Science, Google Scholar, Embase, and CENTRAL
      (the Cochrane Library 2014, issue 8). We reviewed four major guidelines that are
      available regarding (potential) RT recipients. The methodology was in accordance
      with the Cochrane Handbook for Systematic Reviews of Interventions and written
      based on the PRISMA statement. The quality assessment of studies was performed by
      using the GRADE tool. A meta-analysis was performed using Review Manager 5.3.
      Random-effects models were used. RESULTS: After identifying 5,526 studies
      addressing this topic, 56 studies were included. We extracted data for 37 outcome
      measures (including data of more than 209,000 RT recipients), of which 26 could
      be meta-analysed. The following outcome measures demonstrated significant
      differences in favour of low BMI (<30) recipients: mortality (RR = 1.52), delayed
      graft function (RR = 1.52), acute rejection (RR = 1.17), 1-, 2-, and 3-year graft
      survival (RR = 0.97, 0.95, and 0.97), 1-, 2-, and 3-year patient survival (RR =
      0.99, 0.99, and 0.99), wound infection and dehiscence (RR = 3.13 and 4.85), NODAT
      (RR = 2.24), length of hospital stay (2.31 days), operation duration (0.77
      hours), hypertension (RR = 1.35), and incisional hernia (RR = 2.72). However,
      patient survival expressed in hazard ratios was in significant favour of high BMI
      recipients. Differences in other outcome parameters were not significant.
      CONCLUSIONS: Several of the pooled outcome measurements show significant benefits
      for 'low' BMI (<30) recipients. Therefore, we postulate that ESRD patients with a
      BMI >30 preferably should lose weight prior to RT. If this cannot be achieved
      with common measures, in morbidly obese RT candidates, bariatric surgery could be
      considered.

PMID- 25963134
TI  - Prevalence and antimicrobial susceptibility profile of listeria species from
      ready-to-eat foods of animal origin in Gondar Town, Ethiopia.
AB  - BACKGROUND: Listeriosis, mostly caused by Listeria monocytogenes species, has
      become a major concern to public health authorities due to its clinical severity
      and high mortality rate, particularly in high risk groups. Currently, there is
      limited information regarding the prevalence and antimicrobial susceptibility
      profiles of listeria species in ready-to-eat foods of animal origin in Gondar
      town, Ethiopia. The aim of this study was to determine the prevalence and
      antimicrobial susceptibility pattern of Listeria species isolated from ready-to
      eat food of animal origin from public dinning places in Gondar town, Ethiopia. A
      cross sectional study on ready-toeat foods of animal origin sampled from major
      supermarkets, butcher shops, pastry shops, restaurants and hotels was carried
      out. Culture, biochemical and sugar tests were conducted for listeria species
      identification and disc diffusion test was performed to study the antimicrobial
      susceptibility profiles of the isolates. RESULTS: Out of 384 food samples
      examined, 96 (25%) were positive for Listeria species. Listeria monocytogenes was
      detected in 24 (6.25%) of the samples. Listeria monocytogenes was isolated from
      cake, raw meat, ice cream, minced beef, fish, unpasteurized milk and pizza in
      that order from higher to lower rate. Assessment of antimicrobial susceptibility
      profile of L. monocytogenes revealed the presence of four multi-drug resistant
      isolates. The higher resistance rate was recorded for penicillin, nalidixic acid,
      tetracycline and chloramphenicol, in decreasing order. All L. monocytogenes
      identified in the current study were sensitive to amoxicillin, cephalothin,
      cloxacillin, sulfamethoxazole, gentamicin and vancomycin. CONCLUSIONS: The
      presence of L. monocytogenes including drug resistant and multidrug resistant
      isolates in some ready-to-eat food items is an indicator of the presence of
      public health hazards to the consumer, particularly to the high-risk groups.
      Hence awareness creation on food safety and implementation of regulations about
      the use of drugs in humans and animals is strongly recommended.

PMID- 25963135
TI  - Retirement due to disabilities in patients with type 1 diabetes a nationwide
      multicenter survey in Brazil.
AB  - BACKGROUND: There is scarcity of data concerning retirement and workforce loss
      exclusively in patients with type 1 diabetes. The aim of this study was to
      evaluate the prevalence, causes, and predictors of retirement in patients with
      type 1 diabetes in Brazil. METHODS: This was a multicenter cross-sectional study
      conducted between December 2008 and December 2010 in 28 public clinics in 20
      Brazilian cities. Data were obtained from 3,180 patients aged 22 +/- 11.7 years;
      56.3% of the participants were female, and 57.4% were Caucasians. The mean time
      since diabetes diagnosis was 10.3 +/- 8.1 years. Patients' information (clinical
      factors and retirement data) was obtained through a questionnaire and a chart
      review. Patients were retired by diabetes according to the Brazilian Institute of
      Social Security's criteria that takes in account the presence of diabetes-related
      chronic complications certified by a doctor, excluding any personal reason or
      another health condition besides diabetes. Both quantitative and qualitative
      tests were employed, and a multivariate logistic regression model was performed
      to identify the factors associated with retirement due to disabilities in
      patients with type 1 diabetes. RESULTS: The overall frequency of retirement was
      4.2%, with no difference between genders. The mean age of retirement was 35.5 +/-
      9.3 years, resulting in 17.5 +/- 9.1 years of workforce losses. These patients
      had a significantly higher prevalence of severe hypoglycemia, proliferative and
      non-proliferative retinopathy, foot disorders, chronic or end-stage renal disease
      requiring dialysis or transplantation, cataracts, glaucoma, psychological
      disorders, hypertension, and overweight/obesity than did the employed patients.
      Multivariate logistic regression analysis with retirement as the dependent
      variable showed adjusted odds ratios (ORs) of 4.87 (2.66-8.78) for the presence
      of microvascular complications and 3.7 (2.04-6.70) for macrovascular
      complications. CONCLUSIONS: Retirement due to disabilities occurred in 4.2% of
      Brazilian patients with type 1 diabetes at an early age and is strongly
      associated with diabetes-related chronic complications. Health care workers
      should thus reevaluate the quality of care given to these patients.

PMID- 25963136
TI  - Non-sentinel lymph node analysis with one-step nucleic acid amplification in
      breast cancer patients.
AB  - BACKGROUND: One-step nucleic acid amplification (OSNA) examines lymph node
      metastasis in a semiquantitative manner with molecular biology techniques. In
      this study, we conducted a whole-node analysis of non-sentinel lymph nodes (SLNs)
      using the OSNA method in SLN metastasis-positive breast cancer patients. METHODS:
      With the OSNA method, we compared the rates of positivity of non-SLN metastasis
      in cases with both SLN micro- and macrometastases. RESULTS: The rates of non-SLN
      metastasis positivity in those with SLN micrometastasis and macrometastasis were
      44% and 48%, respectively, and this difference was not significant. When the
      study of non-SLN metastasis positivity was focused only on macrometastases, the
      rates of non-SLN metastasis positivity in patients with SLN micrometastasis and
      macrometastasis were 19% and 22%, respectively, and there was no significant
      difference. CONCLUSION: Regardless of the copy number of SLN metastases, non-SLN
      metastases were found in approximately half of the cases.

PMID- 25963137
TI  - CYP2D6*4 polymorphism: A new marker of response to hormonotherapy in male breast
      cancer?
AB  - BACKGROUND: Tamoxifen remains the standard hormonotherapy for Male breast cancer
      patients (MBC). Previous studies, in women, tried to evaluate the impact of
      CYP2D6 polymorphisms in tamoxifen efficacy with conflicting results. Herein we
      analyze the relation between CYP2D6*4 polymorphism and survival in MBC patients.
      PATIENTS AND METHODS: Fifty-three patients, proposed to tamoxifen in adjuvant
      setting, were enrolled. Clinical information was collected from records and
      histological revision with additional immunochemistry analysis was done to better
      characterize the tumors. Comprehensive CYP2D6*4 genotyping from blood or tumor
      tissue was performed and translated into two predicted metabolic activity groups.
      RESULTS: Patients included in the two CYP2D6*4 groups did not differ concerning
      to age, histological characteristics, and primary treatments performed. Median
      age at diagnosis was 63 years-old and patients were submitted at least to
      mastectomy and adjuvant hormonotherapy. Recurrence was observed in 7 patients
      (13.2%) and 13 patients (25.5%) died with a 5-year disease-free survival of
      86.2%. The poorer metabolizer group had a high risk for recurrence (p = 0.034)
      and this outcome effect remains in different subgroups: in tumors larger than 2
      cm (p < 0.001), nodal status, N0 vs N+ (p = 0.04) and in advanced stage, stage
      III (p < 0.001). Poorer metabolizer patients had also a worse overall survival
      when tumors were larger than 2 cm (p = 0.03). CONCLUSIONS: In our series, there
      was an association between CYP2D6*4 polymorphism and a probability of recurrence,
      with a consistent effect in risk groups defined by classic prognostic factors.
      Multicentric studies with larger samples are needed to validate these results.

PMID- 25963138
TI  - Prevalence of dementia in East Asia: a synthetic review of time trends.
AB  - OBJECTIVE: This study aims to synthesise evidence on time trends of dementia
      prevalence in East Asian countries including Japan, China, South Korea and Taiwan
      and assess the impact of the societal changes on future prevalence. METHOD:
      Relevant reviews and recent nationwide studies in East Asia were identified to
      investigate changes in prevalence of dementia over time taking into account the
      potential impact of methodological factors and study designs. RESULTS: The robust
      evidence that has been interpreted to suggest a substantial increasing trend over
      time is less compelling once fundamental differences in study methods and
      populations across individual surveys are considered. In Japan, longitudinal
      studies in small areas suggest the potential increase of prevalence after 2000.
      Increasing trends in China, South Korea and Taiwan over the last 20-30 years are
      based on the literature review without adjustment for methodological differences.
      Economic development and huge societal changes alongside the rise of non
      communicable disease in East Asia could lead to increasing prevalence of dementia
      in the future once those cohorts with high risk of dementia reached their older
      age. CONCLUSION: Current evidence is not sufficient to suggest increasing trends
      of dementia prevalence in East Asia. Longitudinal studies with representative
      samples and stable methodology are needed to provide fundamental information of
      the epidemiology of dementia and identify important risk factors in East Asian
      societies.

PMID- 25963139
TI  - Selection of a breast cancer subpopulation-specific antibody using phage display
      on tissue sections.
AB  - Breast cancer tumors are composed of heterogeneous cell populations. These
      populations display a high variance in morphology, growth and metastatic
      propensity. They respond differently to therapeutic interventions, and some may
      be more prone to cause recurrence. Studying individual subpopulations of breast
      cancer may provide crucial knowledge for the development of individualized
      therapy. However, this process is challenged by the availability of biomarkers
      able to identify subpopulations specifically. Here, we demonstrate an approach
      for phage display selection of recombinant antibody fragments on cryostat
      sections of human breast cancer tissue. This method allows for selection of
      recombinant antibodies binding to antigens specifically expressed in a small part
      of the tissue section. In this case, a CD271(+) subpopulation of breast cancer
      cells was targeted, and these may be potential breast cancer stem cells. We
      isolated an antibody fragment LH 7, which in immunohistochemistry experiments
      demonstrates specific binding to breast cancer subpopulations. The selection of
      antibody fragments directly on small defined areas within a larger section of
      malignant tissue is a novel approach by which it is possible to better target
      cellular heterogeneity in proteomic studies. The identification of novel
      biomarkers is relevant for our understanding and intervention in human diseases.
      The selection of the breast cancer-specific antibody fragment LH 7 may reveal
      novel subpopulation-specific biomarkers, which has the potential to provide new
      insight and treatment strategies for breast cancer. 

PMID- 25963140
TI  - Novel homozygous ALX4 mutation causing frontonasal dysplasia-2 in a patient with
      meningoencephalocele.

PMID- 25963141
TI  - Inflammatory myopathy with anti-signal recognition particle antibodies: case
      series of 100 patients.
AB  - BACKGROUND: Anti-signal recognition particle (SRP) antibodies are used as
      serological markers of necrotizing myopathy, which is characterized by many
      necrotic and regenerative muscle fibers without or with minimal inflammatory cell
      infiltration. The clinical spectrum associated with anti-SRP antibodies seems to
      be broad. OBJECTIVE: To describe the clinical characteristics, autoantibodies
      status, and neurological outcome associated with anti-SRP antibody. METHODS: We
      studied clinical and laboratory findings of 100 patients with inflammatory
      myopathy and anti-SRP antibodies. Anti-SRP antibodies in serum were detected by
      the presence of 7S RNA using RNA immunoprecipitation. In addition, enzyme-linked
      immunosorbent assays (ELISAs) using a 54-kD protein of SRP (SRP54) and 3-hydroxyl
      3-methylglutatyl-coenzyme A reductase (HMGCR) were also conducted. RESULTS: The
      mean onset age of the 61 female and 39 male patients was 51 years (range 4-82
      years); duration >= 12 months before diagnosis was seen in 23 cases. All patients
      presented limbs weakness; 63 had severe weakness, 70 neck weakness, 41 dysphagia,
      and 66 muscle atrophy. Extramuscular symptoms and associated disorders were
      infrequent. Creatine kinase levels were mostly more than 1000 IU/L. Histological
      diagnosis showed 84 patients had necrotizing myopathy, and apparent cell
      infiltration was observed in 16 patients. Anti-SRP54 antibodies were undetectable
      in 18 serum samples with autoantibodies to 7S RNA. Anti-HMGCR antibodies were
      positive in 3 patients without the statin treatment, however, were negative in 5
      patients with statin-exposure at disease onset. All but 3 patients were treated
      by corticosteroids and 62 (77 %) of these 81 patients required additional
      immunotherapy. After 2-years treatment, 22 (27 %) of these 81 patients had poor
      neurological outcomes with modified Rankin scale scores of 3-5. Multivariate
      analysis revealed that pediatric disease onset was associated with the poor
      outcomes. CONCLUSION: Anti-SRP antibodies are associated with different clinical
      courses and histological presentations.

PMID- 25963143
TI  - Melatonin Regulates Angiogenic Factors under Hypoxia in Breast Cancer Cell Lines.
AB  - Angiogenesis is the process of new blood vessel formation, regulated by a number
      of pro- and antiangiogenic factors and usually begins in response to hypoxia.
      Exogenous administration of melatonin has shown numerous anti-tumor effects and
      appears to inhibit tumor angiogenesis. However, many factors involved in the anti
      angiogenic effect of melatonin are still under investigation. Here, we evaluate
      the effects of melatonin on cell viability and expression of angiogenic factors
      in MCF-7 and MDA-MB-231 breast cancer cells under hypoxic conditions. Cell
      viability was investigated by MTT and gene and protein expression of the hypoxia
      inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF
      A) were verified by qPCR and immunocytochemistry after melatonin treatment (1 mM)
      under hypoxic conditions. Additionally, a protein array with 20 different
      cytokines/factors was performed on tumor cell lysates. The results showed that 1
      mM of melatonin reduced the viability of MCF-7 and MDA-MB-231 cells (p < .05).
      This treatment also decreased both gene and protein expression of HIF-1alpha and
      VEGF-A under hypoxic conditions (p < .05). Among the proteins evaluated by
      protein array, melatonin treatment during hypoxia reduced VEGF-C, VEGFR receptors
      (VEGFR2 and VEGFR3), matrix metalloproteinase 9 (MMP9) and Angiogenin in MCF-7
      cells. In MDA-MB-231 cells, a significant decrease was observed in VEGFR2,
      epidermal growth factor receptor (EGFR) and Angiogenin (p < .05). Taken together,
      these results showed that melatonin acts in the regulation of angiogenic factors
      in breast tumor cells and suggests an anti-angiogenic activity, particularly
      under hypoxic conditions. 

PMID- 25963142
TI  - The microfibril-associated glycoproteins (MAGPs) and the microfibrillar niche.
AB  - The microfibril-associated glycoproteins MAGP-1 and MAGP-2 are extracellular
      matrix proteins that interact with fibrillin to influence microfibril function.
      The two proteins are related through a 60 amino acid matrix-binding domain but
      their sequences differ outside of this region. A distinguishing feature of both
      proteins is their ability to interact with TGFbeta family growth factors, Notch
      and Notch ligands, and multiple elastic fiber proteins. MAGP-2 can also interact
      with alphavbeta3 integrins via a RGD sequence that is not found in MAGP-1.
      Morpholino knockdown of MAGP-1 expression in zebrafish resulted in abnormal
      vessel wall architecture and altered vascular network formation. In the mouse,
      MAGP-1 deficiency had little effect on elastic fibers in blood vessels and lung
      but resulted in numerous unexpected phenotypes including bone abnormalities,
      hematopoietic changes, increased fat deposition, diabetes, impaired wound repair,
      and a bleeding diathesis. Inactivation of the gene for MAGP-2 in mice produced a
      neutropenia yet had minimal effects on bone or adipose homeostasis. Double
      knockouts had phenotypes characteristic of each individual knockout as well as
      several additional traits only seen when both genes are inactivated. A common
      mechanism underlying all of the traits associated with the knockout phenotypes is
      altered TGFbeta signaling. This review summarizes our current understanding of
      the function of the MAGPs and discusses ideas related to their role in growth
      factor regulation. 

PMID- 25963144
TI  - NEU1 Sialidase Regulates Membrane-tethered Mucin (MUC1) Ectodomain Adhesiveness
      for Pseudomonas aeruginosa and Decoy Receptor Release.
AB  - Airway epithelia express sialylated receptors that recognize exogenous danger
      signals. Regulation of receptor responsiveness to these signals remains
      incompletely defined. Here, we explore the mechanisms through which the human
      sialidase, neuraminidase-1 (NEU1), promotes the interaction between the
      sialoprotein, mucin 1 (MUC1), and the opportunistic pathogen, Pseudomonas
      aeruginosa. P. aeruginosa flagellin engaged the MUC1 ectodomain (ED), increasing
      NEU1 association with MUC1. The flagellin stimulus increased the association of
      MUC1-ED with both NEU1 and its chaperone/transport protein, protective
      protein/cathepsin A. Scatchard analysis demonstrated NEU1-dependent increased
      binding affinity of flagellin to MUC1-expressing epithelia. NEU1-driven MUC1-ED
      desialylation rapidly increased P. aeruginosa adhesion to and invasion of the
      airway epithelium. MUC1-ED desialylation also increased its shedding, and the
      shed MUC1-ED competitively blocked P. aeruginosa adhesion to cell-associated MUC1
      ED. Levels of desialylated MUC1-ED were elevated in the bronchoalveolar lavage
      fluid of mechanically ventilated patients with P. aeruginosa airway colonization.
      Preincubation of P. aeruginosa with these same ex vivo fluids competitively
      inhibited bacterial adhesion to airway epithelia, and MUC1-ED immunodepletion
      completely abrogated their inhibitory activity. These data indicate that a
      prokaryote, P. aeruginosa, in a ligand-specific manner, mobilizes eukaryotic NEU1
      to enhance bacterial pathogenicity, but the host retaliates by releasing MUC1-ED
      into the airway lumen as a hyperadhesive decoy receptor. 

PMID- 25963145
TI  - Functional and Biochemical Characterization of Cucumber Genes Encoding Two Copper
      ATPases CsHMA5.1 and CsHMA5.2.
AB  - Plant copper P1B-type ATPases appear to be crucial for maintaining copper
      homeostasis within plant cells, but until now they have been studied mostly in
      model plant systems. Here, we present the molecular and biochemical
      characterization of two cucumber copper ATPases, CsHMA5.1 and CsHMA5.2,
      indicating a different function for HMA5-like proteins in different plants. When
      expressed in yeast, CsHMA5.1 and CsHMA5.2 localize to the vacuolar membrane and
      are activated by monovalent copper or silver ions and cysteine, showing different
      affinities to Cu(+) (Km ~1 or 0.5 MUM, respectively) and similar affinity to
      Ag(+) (Km ~2.5 MUM). Both proteins restore the growth of yeast mutants sensitive
      to copper excess and silver through intracellular copper sequestration,
      indicating that they contribute to copper and silver detoxification.
      Immunoblotting with specific antibodies revealed the presence of CsHMA5.1 and
      CsHMA5.2 in the tonoplast of cucumber cells. Interestingly, the root-specific
      CsHMA5.1 was not affected by copper stress, whereas the widely expressed CsHMA5.2
      was up-regulated or down-regulated in roots upon copper excess or deficiency,
      respectively. The copper-induced increase in tonoplast CsHMA5.2 is consistent
      with the increased activity of ATP-dependent copper transport into tonoplast
      vesicles isolated from roots of plants grown under copper excess. These data
      identify CsHMA5.1 and CsHMA5.2 as high affinity Cu(+) transporters and suggest
      that CsHMA5.2 is responsible for the increased sequestration of copper in
      vacuoles of cucumber root cells under copper excess.

PMID- 25963146
TI  - Human DNA Polymerase nu Catalyzes Correct and Incorrect DNA Synthesis with High
      Catalytic Efficiency.
AB  - DNA polymerase nu (pol nu) is a low fidelity A-family polymerase with a putative
      role in interstrand cross-link repair and homologous recombination. We carried
      out pre-steady-state kinetic analysis to elucidate the kinetic mechanism of this
      enzyme. We found that the mechanism consists of seven steps, similar that of
      other A-family polymerases. pol nu binds to DNA with a Kd for DNA of 9.2 nm, with
      an off-rate constant of 0.013 s(-1)and an on-rate constant of 14 MUm(-1) s(-1).
      dNTP binding is rapid with Kd values of 20 and 476 MUm for the correct and
      incorrect dNTP, respectively. Pyrophosphorylation occurs with a Kd value for PPi
      of 3.7 mm and a maximal rate constant of 11 s(-1). Pre-steady-state kinetics,
      examination of the elemental effect using dNTPalphaS, and pulse-chase experiments
      indicate that a rapid phosphodiester bond formation step is flanked by slow
      conformational changes for both correct and incorrect base pair formation. These
      experiments in combination with computer simulations indicate that the first
      conformational change occurs with rate constants of 75 and 20 s(-1); rapid
      phosphodiester bond formation occurs with a Keq of 2.2 and 1.7, and the second
      conformational change occurs with rate constants of 2.1 and 0.5 s(-1), for
      correct and incorrect base pair formation, respectively. The presence of a
      mispair does not induce the polymerase to adopt a low catalytic conformation. pol
      nu catalyzes both correct and mispair formation with high catalytic efficiency. 

PMID- 25963147
TI  - Dual Effect of Phosphate Transport on Mitochondrial Ca2+ Dynamics.
AB  - The large inner membrane electrochemical driving force and restricted volume of
      the matrix confer unique constraints on mitochondrial ion transport. Cation
      uptake along with anion and water movement induces swelling if not compensated by
      other processes. For mitochondrial Ca(2+) uptake, these include activation of
      countertransporters (Na(+)/Ca(2+) exchanger and Na(+)/H(+) exchanger) coupled to
      the proton gradient, ultimately maintained by the proton pumps of the respiratory
      chain, and Ca(2+) binding to matrix buffers. Inorganic phosphate (Pi) is known to
      affect both the Ca(2+) uptake rate and the buffering reaction, but the role of
      anion transport in determining mitochondrial Ca(2+) dynamics is poorly
      understood. Here we simultaneously monitor extra- and intra-mitochondrial Ca(2+)
      and mitochondrial membrane potential (DeltaPsim) to examine the effects of anion
      transport on mitochondrial Ca(2+) flux and buffering in Pi-depleted guinea pig
      cardiac mitochondria. Mitochondrial Ca(2+) uptake proceeded slowly in the absence
      of Pi but matrix free Ca(2+) ([Ca(2+)]mito) still rose to ~50 MUm. Pi (0.001-1
      mm) accelerated Ca(2+) uptake but decreased [Ca(2+)]mito by almost 50% while
      restoring DeltaPsim. Pi-dependent effects on Ca(2+) were blocked by inhibiting
      the phosphate carrier. Mitochondrial Ca(2+) uptake rate was also increased by
      vanadate (Vi), acetate, ATP, or a non-hydrolyzable ATP analog (AMP-PNP), with
      differential effects on matrix Ca(2+) buffering and DeltaPsim recovery.
      Interestingly, ATP or AMP-PNP prevented the effects of Pi on Ca(2+) uptake. The
      results show that anion transport imposes an upper limit on mitochondrial Ca(2+)
      uptake and modifies the [Ca(2+)]mito response in a complex manner.

PMID- 25963150
TI  - The determination of DNA methyltransferase activity by quenching of tris(2,2'
      bipyridine)ruthenium electrogenerated chemiluminescence with ferrocene.
AB  - An electrogenerated chemiluminescence (ECL) biosensing method for the
      determination of DNA methyltransferase activity is developed by the quenching of
      tris(2,2'-bipyridine)ruthenium ECL by ferrocene, and it is demonstrated that the
      ECL biosensing method measures DNA adenine methylation methyltransferase over a
      dynamic concentration range (0.1 U mL(-1)-100 U mL(-1)) with an extremely low
      detection limit of 0.03 U mL(-1), using gold nanoparticles and a quenching ECL
      signal produced by a chemical quencher such as ferrocene. 

PMID- 25963149
TI  - Down-Regulating the Expression of 53 Soybean Transcription Factor Genes Uncovers
      a Role for SPEECHLESS in Initiating Stomatal Cell Lineages during Embryo
      Development.
AB  - We used an RNA interference screen to assay the function of 53 transcription
      factor messenger RNAs (mRNAs) that accumulate specifically within soybean
      (Glycine max) seed regions, subregions, and tissues during development. We show
      that basic helix-loop-helix (bHLH) transcription factor genes represented by
      Glyma04g41710 and its paralogs are required for the formation of stoma in leaves
      and stomatal precursor complexes in mature embryo cotyledons. Phylogenetic
      analysis indicates that these bHLH transcription factor genes are orthologous to
      Arabidopsis (Arabidopsis thaliana) SPEECHLESS (SPCH) that initiate asymmetric
      cell divisions in the leaf protoderm layer and establish stomatal cell lineages.
      Soybean SPCH (GmSPCH) mRNAs accumulate primarily in embryo, seedling, and leaf
      epidermal layers. Expression of Glyma04g41710 under the control of the SPCH
      promoter rescues the Arabidopsis spch mutant, indicating that Glyma04g41710 is a
      functional ortholog of SPCH. Developing soybean embryos do not form mature stoma,
      and stomatal differentiation is arrested at the guard mother cell stage. We
      analyzed the accumulation of GmSPCH mRNAs during soybean seed development and
      mRNAs orthologous to MUTE, FAMA, and inducer of C-repeat/dehydration responsive
      element-binding factor expression1/scream2 that are required for stoma formation
      in Arabidopsis. The mRNA accumulation patterns provide a potential explanation
      for guard mother cell dormancy in soybean embryos. Our results suggest that
      variation in the timing of bHLH transcription factor gene expression can explain
      the diversity of stomatal forms observed during plant development.

PMID- 25963151
TI  - Parietal atretic cephalocele: Associated cerebral anomalies identified by CT and
      MR imaging.
AB  - We describe a case of atretic cephalocele (AC) characterized by the presence of
      various cerebral anomalies of different midline structures. In our patient the
      presence of a parietal AC was associated with an embryonic position of the
      straight sinus, fenestration of the superior sagittal sinus, an abnormal
      insertion of the cerebellar tentorium with prominence of the superior cerebellar
      cistern and a septum pellucidum cyst. These findings, associated with AC, could
      lead to a worse prognosis with regard to neurodevelopmental milestones. This
      suggests that even if AC is a benign lesion, a complete evaluation of the brain
      structures should always be performed in these young patients. 

PMID- 25963152
TI  - A Rare Association of Trigeminal Autonomic Cephalgia: Pontine Capillary
      Telangiectasia.
AB  - This report describes a case of pontine capillary telangiectasia in a 43-year-old
      woman with a clinical diagnosis of trigeminal autonomic cephalgia. The possible
      association with pontine capillary telangiectasia and trigeminal autonomic
      cephalgia is discussed. 

PMID- 25963153
TI  - Functional Neuroimaging: Fundamental Principles and Clinical Applications.
AB  - Functional imaging modalities, such as functional magnetic resonance imaging
      (fMRI) and diffusion tensor imaging (DTI), are rapidly changing the scope and
      practice of neuroradiology. While these modalities have long been used in
      research, they are increasingly being used in clinical practice to enable
      reliable identification of eloquent cortex and white matter tracts in order to
      guide treatment planning and to serve as a diagnostic supplement when traditional
      imaging fails. An understanding of the scientific principles underlying fMRI and
      DTI is necessary in current radiological practice. fMRI relies on a compensatory
      hemodynamic response seen in cortical activation and the intrinsic discrepant
      magnetic properties of deoxy- and oxyhemoglobin. Neuronal activity can be
      indirectly visualized based on a hemodynamic response, termed neurovascular
      coupling. fMRI demonstrates utility in identifying areas of cortical activation
      (i.e., task-based activation) and in discerning areas of neuronal connectivity
      when used during the resting state, termed resting state fMRI. While fMRI is
      limited to visualization of gray matter, DTI permits visualization of white
      matter tracts through diffusion restriction along different axes. We will discuss
      the physical, statistical and physiological principles underlying these
      functional imaging modalities and explore new promising clinical applications.

PMID- 25963155
TI  - Neurocutaneous melanosis: Review of a rare non-familial neuroectodermal dysplasia
      with newer association of cerebellopontine angle cistern lipoma.
AB  - Neurocutaneous melanosis is a rare neuroectodermal dysplasia with a grave
      prognosis. It is actually a disorder of neuronal migration at the time of the
      embryogenesis hence classified as a neurocristopathy. The patients are initially
      identified by the skin manifestations of the disease in the form of melanocytic
      naevus which can be hairy or non-hairy. These patients may or may not present
      with neurological symptoms but often show CNS abnormalities especially on MRI of
      the brain and the spine. A lot has been described about the disease since the
      first case described by Rokitansky in 1861, but every time a new CNS pathology is
      being added to the long list of currently documented pathologies. Herein we
      describe a case of a 5 yr old boy with seizures and hairy melanocytic naevus over
      the trunk and back who was diagnosed as a case of Neurocutaneous melanosis on
      subsequent evaluation by CT and MRI. We also describe the new association of CP
      angle cistern lipoma with neurocutaneous melanosis. 

PMID- 25963154
TI  - Diffusion characteristics of pediatric pineal tumors.
AB  - BACKGROUND: Diffusion weighted imaging (DWI) has been shown to be helpful in
      characterizing tumor cellularity, and predicting histology. Several works have
      evaluated this technique for pineal tumors; however studies to date have not
      focused on pediatric pineal tumors. OBJECTIVE: We evaluated the diffusion
      characteristics of pediatric pineal tumors to confirm if patterns seen in studies
      using mixed pediatric and adult populations remain valid. MATERIALS AND METHODS:
      This retrospective study was performed after Institutional Review Board approval.
      We retrospectively evaluated all patients 18 years of age and younger with pineal
      tumors from a single institution where preoperative diffusion weighted imaging as
      well as histologic characterization was available. RESULTS: Twenty patients (13
      male, 7 female) with pineal tumors were identified: seven with pineoblastoma,
      four with Primitive Neuroectodermal Tumor (PNET), two with other pineal tumors,
      and seven with germ cell tumors including two germinomas, three teratomas, and
      one mixed germinoma-teratoma. The mean apparent diffusion coefficient (ADC)
      values in pineoblastoma (544 +/- 65 * 10-6 mm2/s) and pineoblastoma/PNET (595 +/-
      144 * 10-6 mm2/s) was lower than that of the germ cell tumors (1284 +/- 334 * 10
      6 mm2/s; p < 0.0001 vs pineoblastoma). One highly cellular germinoma had an ADC
      value of 694 * 10-6 mm2/s. CONCLUSION: ADC values can aid in differentiation of
      pineoblastoma/PNET from germ cell tumors in a population of children with pineal
      masses.

PMID- 25963156
TI  - Intraorbital Granular Cell Tumor Ophthalmologic and Radiologic Findings.
AB  - Granular cell tumor is a rare soft tissue neoplasm that commonly affects the head
      and neck regions. We describe a case of a granular cell tumor of the orbit
      including its clinical presentation, histopathology, and magnetic resonance
      imaging findings. 

PMID- 25963157
TI  - Brain MR diffusion tensor imaging in Kennedy's disease.
AB  - INTRODUCTION: Kennedy's disease (KD) is a progressive degenerative disorder
      affecting lower motor neurons. We investigated the correlation between disease
      severity and whole brain white matter microstructure, including upper motor
      neuron tracts, by using diffusion-tensor imaging (DTI) in eight patients with KD
      in whom disease severity was evaluated using the Amyotrophic Lateral Sclerosis
      Functional Rating Scale (ALSFRS). METHODS: From DTI acquisitions we obtained maps
      of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (L1) and
      radial diffusivities (L2, L3). We then employed tract-based spatial statistics
      (TBSS) to investigate within-patient correlations of DTI invariants with ALSFRS
      and disease duration (DD). RESULTS: We found a significant correlation between
      low ALSFRS and 1) low FA values in association commissural and projection fibers,
      and 2) high L3 values in commissural tracts and fronto-parietal white matter.
      Additionally, we found a significant association between longer DD and 1) low FA
      in the genu and body of corpus callosum, association fibers and midbrain and 2)
      high L1 in projection and association tracts. CONCLUSIONS: The associations
      between clinical variables and white matter microstructural changes in areas
      thought to be spared by the disease process support the hypothesis of a
      multisystem involvement in the complex pathogenic mechanisms responsible for the
      clinical disability of these patients.

PMID- 25963158
TI  - Dural enhancement and thickening in acute mastoiditis.
AB  - Dural enhancement and thickening in imaging studies observed in acute mastoiditis
      patients is an uncommon phenomenon. It is infrequently seen in dural sinus
      thrombosis, and may be caused by infiltration of inflammatory cells and an
      increased number of thin-walled blood vessels. We present a three-year-old boy
      who presented with acute mastoiditis, complicated by subperiosteal abscess.
      Computerized tomography (CT) demonstrated subperiosteal abscess, and the child
      underwent mastoidectomy. Despite adequate treatment, symptoms worsened and
      neurological sequelae were suspected. CT and magnetic resonance imaging (MRI)
      studies demonstrated an atypical dural enhancement at the sigmoid perisinus and
      suboccipital abscess. The child underwent revision mastoidectomy and drainage of
      the abscess. Following the second procedure, resolution of symptoms was noted.
      Follow-up MRI did not demonstrate any dural pathologies. 

PMID- 25963159
TI  - Subpial Hematoma and Extravasation in the Interhemispheric Fissure with
      Subarachnoid Hemorrhage.
AB  - A recent report on computed tomography (CT) findings of contrast extravasation in
      subarachnoid hemorrhage (SAH) with Sylvian hematoma suggests that the occurrence
      of the hematoma is secondary to bleeding in the subpial space. Our patient was in
      his sixties and was admitted to the hospital because of loss of consciousness
      (Glasgow Coma Scale E4V1M4). SAH was diagnosed in plain head CT, and growing
      hematomas were observed in the Sylvian and interhemispheric fissures following a
      subarachnoid hemorrhage. CT angiography (CTA) using a dual-phase scan protocol
      revealed contrast extravasation in both the fissures in the latter phase, and
      hematoma in the interhemispheric fissure contained multiple bleeding points. This
      case indicates that the occurrence of subpial hematoma such as Sylvian hematoma
      can be a secondary event following subpial bleeding from damaged small vessels
      elsewhere in the cranium. Instead of four-dimensional (4D) CT, the dual-phase CTA
      technique may help detect minor extravasations with usual helical CT scanner. 

PMID- 25963160
TI  - Application of surface enhanced Raman scattering to the solution based detection
      of a popular legal high, 5,6-methylenedioxy-2-aminoindane (MDAI).
AB  - The ever increasing numbers and users of designer drugs means that analytical
      techniques have to evolve constantly to facilitate their identification and
      detection. We report that surface enhanced Raman scattering (SERS) offers a
      relatively fast and inexpensive method for the detection of MDAI at low
      concentrations. Careful optimisation of the silver sol, and salt concentrations
      was undertaken to ensure the SERS analysis was both reproducible and sensitive.
      The optimised system demonstrated acceptable peak variations of less than 15% RSD
      and resulted in a detection limit of just 8 ppm (5.4 * 10(-5) M). 

PMID- 25963161
TI  - The patient-breast cancer care pathway: how could it be optimized?
AB  - BACKGROUND: A care pathway is defined as patient-focused global care that
      addresses temporal (effective and coordinated management throughout the illness)
      and spatial issues (treatment is provided near the health territory in or around
      the patient's home). Heterogeneity of the care pathways in breast cancer (BC) is
      presumed but not well evaluated. The OPTISOINS01 study aims to assess every
      aspect of the care pathway for early BC patients using a temporal and spatial
      scope. METHODS/DESIGN: An observational, prospective, multicenter study in a
      regional health territory (Ile-de-France, France) in different types of
      structures: university or local hospitals and comprehensive cancer centers. We
      will include and follow during 1 year 1,000 patients. The study consists of 3
      work-packages: - Cost of pathway The aim of this WP is to calculate the overall
      costs of the early BC pathway at 1 year from different perspectives (society,
      health insurance and patient) using a cost-of-illness analysis. Using a bottom-up
      method, we will assess direct costs, including medical direct costs and
      nonmedical direct costs (transportation, home modifications, home care services,
      and social services), and indirect costs (loss of production). - Patient
      satisfaction and work reintegration Three questionnaires will assess the
      patients' satisfaction and possible return to work: the occupational
      questionnaire for employed women; the questionnaire on the need for supportive
      care, SCNS-SF34 ('breast cancer' module, SCNS-BR8); and the OUTPASSAT-35
      questionnaire. - Quality, coordination and access to innovation Quality will be
      evaluated based on visits and treatment within a set period, whether the setting
      offers a multidisciplinary consultative framework, the management by nurse
      coordinators, the use of a personalized care plan, the provision of information
      via documents about treatments and the provision of supportive care. The
      coordination between structures and caregivers will be evaluated at several
      levels. Day surgery, home hospitalization and one-stop breast clinic visits will
      be recorded to assess the patient's access to innovation. DISCUSSION: The
      assessment of care pathways encourages the implementation of new payment models.
      Our approach could help health care professionals and policymakers to establish
      other cost-of-illness studies and plan the allocation of resources on a patient
      basis rather than a visit basis.

PMID- 25963162
TI  - Prenylated polyphenolic compounds from Glycyrrhiza iconica and their
      antimicrobial and antioxidant activities.
AB  - A new prenylated isoflavan, iconisoflavan (1), and a new prenylated isoflav-3
      ene, iconisoflaven (2) were isolated from the roots of Glycyrrhiza iconica
      together with four known ones namely (3S)-licoricidin (3), licorisoflavan A (4),
      topazolin (5) and glycycoumarin (6). The structures were elucidated on the basis
      of extensive spectroscopic analysis including 1D and 2D NMR as well as HR-MS.
      Furthermore, the absolute configurations of compounds 1, 3 and 4 were established
      by electronic circular dichroism (ECD). All the isolated compounds (1-6) were
      evaluated for their in vitro antimicrobial activities against five pathogenic
      bacteria and one yeast (Candida albicans) using an in vitro microdilution method.
      Compounds 1 and 3-5 displayed significant activity against Salmonella typhimurium
      ATCC 13311 with MIC values ranging from 2 to 8 MUg/mL. Additionally, all
      compounds were screened for their in vitro free radical scavenging activities
      using an in vitro microdilution DPPH assay spectrofotometrically. The tested
      compounds exhibited IC50 values in the range of 0.18-0.56 mg/mL, suggesting an
      activity comparable with that of ascorbic acid (IC50: 0.07 mg/mL). To the best of
      our knowledge, the present study constitutes the first phytochemical and
      bioactivity investigation on G. iconica.

PMID- 25963163
TI  - Two novel missense substitutions in the VSX1 gene: clinical and genetic analysis
      of families with Keratoconus from India.
AB  - BACKGROUND: Visual system homeobox gene (VSX1) plays a major role in the early
      development of craniofacial and ocular tissues including cone opsin gene in the
      human retina. To date, few disease-causing mutations of VSX1 have been linked to
      familial and sporadic keratoconus (KC) in humans. In this study, we describe the
      clinical features and screening for VSX1 gene in families with KC from India.
      METHODS: Clinical data and genomic DNA were collected from patients with
      clinically diagnosed KC and their family members. The study was conducted on 20
      subjects of eight families from India. The coding exons of VSX1 gene were
      amplified using PCR and amplicons were analyzed by direct sequencing. Predictive
      effect of the mutations was performed using Polyphen-2, SIFT and mutation
      assessor algorithms. Additionally, haplotypes of VSX1 gene were constructed for
      affected and unaffected individuals using SNPs. RESULTS: In the coding region of
      VSX1, one novel missense heterozygous change (p.Leu268His) was identified in five
      KC patients from two unrelated families. Another family of three members had a
      novel heterozygous change (p.Ser251Thr). These variants co-segregated with the
      disease phenotype in all affected individuals but not in the unaffected family
      members and 105 normal controls. In silico analysis suggested that p.Leu268His
      could have a deleterious effect on the protein coded by VSX1, while p.Ser251Thr
      has a neutral effect on the functional properties of VSX1. Haplotype examination
      revealed common SNPs around the missense change (p.Leu268His) in two unrelated KC
      families. CONCLUSIONS: In this study, we add p.Leu268His, a novel missense
      variation in the coding region of VSX1 to the existing repertoire of VSX1 coding
      variations observed in Indian patients with the characteristic phenotype of KC.
      The variant p.Ser251Thr might be a benign polymorphism, but further biophysical
      studies are necessary to evaluate its molecular mechanism. The shared haplotype
      by two families with the same variant suggests the possibility of a founder
      effect, which requires further elucidation. We suggest that p.Leu268His might be
      involved in the pathogenesis of KC, which may help in the genetic counselling of
      patients and their family.

PMID- 25963165
TI  - Variability in same-day discharge for pediatric appendicitis.
AB  - BACKGROUND: Recent single-institutional data point to the feasibility of same-day
      discharge (SDD) after appendectomy for nonperforated appendicitis and its
      potential as a quality-of-care indicator. Opportunities for SDD are greatest the
      sooner the appendectomy is performed after admission. We examine a national
      database to assess the pattern of SDD utilization among children who underwent
      appendectomy on the day of admission and potential limitations to SDD. METHODS:
      The 2009 Kids Inpatient Database (KID) was queried for children with a diagnosis
      of acute appendicitis who had appendectomy. Exclusion criteria included those
      children with perforated appendicitis or those in whom the procedure code was
      missing. Day from admission to procedure day and total length of stay (LOS) were
      then analyzed by demographics, type of procedure (laparoscopic versus open),
      children's hospital designation, and hospital region. After stratifying all
      patients undergoing appendectomy on day of admission into two groups by LOS (<=1
      d, SDD versus >1 d, non-SDD), a multivariate analysis was then performed to
      determine the predictors of SDD. RESULTS: A total of 38,959 records, representing
      a weighted estimate of 56,077 patients with a diagnosis of nonperforated
      appendicitis, met the inclusion criteria. Median age was 14 y with interquartile
      range of 10-17 y. Median LOS was 1 d (interquartile range, 1-2 d), and the
      majority (71.8%) had laparoscopic appendectomy. On adjusted analysis,
      laparoscopic cases were 50% less likely to be non-SDD compared with their open
      counterparts (odds ratio [OR], 0.50; 95% confidence interval [CI], 0.47-0.53).
      Compared with Caucasians, significantly more Hispanics (OR, 1.44; 95% CI, 1.36
      1.56) and African Americans (OR, 1.57; 95% CI, 1.42-1.73) were non-SDD. Hospitals
      in the midwest and south were more likely to be non-SDD. CONCLUSIONS: SDD is
      increasingly used for children with nonperforated appendicitis, but there is
      significant variability in the utilization of SDD for different ethnicities and
      hospital regions. These variations need to be further investigated to better
      delineate its potential role as a quality-of-care indicator.

PMID- 25963164
TI  - Effects of a protocol-based management of type A aortic dissections.
AB  - BACKGROUND: Ascending aortic dissections (AADs) require prompt diagnosis and
      surgical treatment. We present the results of implementing a multidisciplinary
      aortic dissection protocol on the outcomes of AAD treatment at a nonteaching
      hospital. METHODS: From January 2002-December 2013, 54 patients with the
      diagnosis of AAD were treated at our institution. Thirty-seven (68.5%) were male
      with a mean age of 62.3 y. Cardiogenic shock was present in 25.9% of patients. An
      AAD protocol, focused on educating physicians on presenting signs and symptoms,
      adequate triaging, and the need for immediate surgical intervention, was
      implemented, alongside the standardization of surgical treatment. We divided the
      cohort into two eras, based on AAD program's implementation in 2006, to better
      assess the impact of this protocol. RESULTS: Patients from the early era had
      significantly longer time from Emergency Department to the operating room, more
      postoperative occurrence of prolonged ventilation, and a longer postoperative
      hospital stay at 8.7 +/- 8 versus 3.1 +/- 2.6 h (P = 0.002), 63% versus 18% (P =
      0.002), and 63% versus 18% (P = 0.002), respectively. The overall mortality for
      the cohort was 9.3%, decreasing from 12.5% before 2006 to 7.9% after 2006.
      CONCLUSIONS: The implementation of a multidisciplinary aortic dissection protocol
      has resulted in faster diagnosis and transport of AAD cases from the emergency
      room to the operating room, improving outcomes. Our data support the concept that
      nonteaching institutions can deliver excellent care to patients with acute aortic
      emergencies.

PMID- 25963166
TI  - Medical students impact laparoscopic surgery case time.
AB  - BACKGROUND: Medical students (MS) are increasingly assuming active roles in the
      operating room. Laparoscopic cases offer unique opportunities for MS
      participation. The aim of this study was to examine associations between the
      presence of MS in laparoscopic cases and operation time and postoperative
      complication rates. MATERIALS AND METHODS: Data from the American College of
      Surgeons National Surgical Quality Improvement Program were linked to operative
      records for nonemergent, inpatient, and laparoscopic general surgery cases at our
      institution from January, 2009-January, 2013. Cases were grouped into eight
      distinct procedure categories. Hospital records provided information on the
      presence of MS. Demographics, comorbidities, intraoperative variables, and
      postoperative complication rates were analyzed. RESULTS: Seven hundred
      laparoscopic cases were included. Controlling for wound class, procedure group,
      and surgeon, MS were associated with an additional 28 min of total operative
      time. The most significant increase occurred between the skin incision and skin
      closure. No significant association between the presence of MS and postoperative
      complications was observed. CONCLUSIONS: This is the first retrospective analysis
      to examine the effect of MS presence during laparoscopic procedures. Increase in
      the operation time associated with the presence of MS should be examined further,
      to optimize the educational experience without incurring increased cost due to
      increased operation time.

PMID- 25963167
TI  - Alterations in hepatic lobar function in regenerating rat liver.
AB  - BACKGROUND: Ligation of a branch of the portal vein redirects portal blood to
      nonligated lobes resulting in lobar hypertrophy. Although the effect of portal
      vein ligation on liver volume is well documented, the parallel alterations in
      liver function are still the subject of controversy. Our aim was to assess the
      time-dependent reactions of regional hepatic function to portal vein ligation by
      selective biliary drainage. METHODS: Male Wistar rats (n = 44) underwent 80%
      portal vein ligation. Before the operation as well as 1, 2, 3, 5, and 7 d after
      circulation, morphology and function (laboratory blood test; hepatic bile flow;
      plasma disappearance rate of indocyanine green; and biliary indocyanine green
      excretion) of the liver were examined. RESULTS: Although portal vein ligation
      affected liver circulation and morphology to a great extent, serum albumin
      levels, bilirubin levels, and total hepatic bile flow did not change
      significantly after the operation. Nevertheless, plasma disappearance rate and
      biliary indocyanine green excretion indicated a temporary impairment of total
      liver function with the lowest value on the second day and normalization by the
      fifth day. Bile production and biliary indocyanine green excretion of ligated
      lobes decreased rapidly after the operation and remained persistently suppressed,
      whereas the secretory function of nonligated lobes--after a temporary decline-
      showed a greater increase than the weight of the lobes. CONCLUSIONS: Portal vein
      ligation induced temporary impairment of total liver function, followed by rapid
      recovery mainly by reason of increase in the function of nonligated lobes.
      Functional increase in nonligated lobes was more pronounced than suggested by the
      degree of volume gain.

PMID- 25963168
TI  - Diagnostic value of serum B7-H4 for hepatocellular carcinoma.
AB  - BACKGROUND: Previous studies have suggested the abnormal expression of soluble B7
      H4 (sB7-H4) in circulation in cancer patients. The aim of present study was to
      examine the sB7-H4 expression in serum and to investigate the correlations
      between sB7-H4 levels and clinicopathologic parameters as well as the survival
      rate of patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS:
      Circulating sB7-H4 levels in blood specimens from 93 patients with HCC and 55
      healthy volunteers were examined by enzyme-linked immunosorbent assay. The
      association of sB7-H4 levels with clinicopathologic factors, overall survival
      (OS), and time to recurrence were statistically analyzed. RESULTS: sB7-H4 levels
      in HCC patients were significantly higher than that in healthy controls (49.12 +/
      3.10 versus 31.66 +/- 2.59 ng/mL, P < 0.001). High sB7-H4 levels were correlated
      with tumor size (P = 0.007), tumor invasion (P = 0.037), tumor differentiation (P
      = 0.044) and tumor-node metastasis stage (P < 0.001). In addition, high sB7-H4
      levels were significantly related to poor OS and higher recurrence probability (P
      = 0.002, P = 0.014, respectively). High sB7-H4 levels were independent prognostic
      factors for both OS (hazard ratio = 2.497; 95% confidence interval, 1.133-3.789;
      P = 0.009) and time to recurrence (hazard ratio = 2.33; 95% confidence interval,
      1.247-4.179; P = 0.008). CONCLUSIONS: Detection of sB7-H4 in serum might serve as
      a clinical predictor in the diagnosis or prediction of clinical outcomes for the
      patients with HCC.

PMID- 25963169
TI  - Analysis of opo cis-regulatory landscape uncovers Vsx2 requirement in early eye
      morphogenesis.
AB  - The self-organized morphogenesis of the vertebrate optic cup entails coupling the
      activation of the retinal gene regulatory network to the constriction-driven
      infolding of the retinal epithelium. Yet the genetic mechanisms underlying this
      coordination remain largely unexplored. Through phylogenetic footprinting and
      transgenesis in zebrafish, here we examine the cis-regulatory landscape of opo,
      an endocytosis regulator essential for eye morphogenesis. Among the different
      conserved enhancers identified, we isolate a single retina-specific element
      (H6_10137) and show that its activity depends on binding sites for the retinal
      determinant Vsx2. Gain- and loss-of-function experiments and ChIP analyses reveal
      that Vsx2 regulates opo expression through direct binding to this retinal
      enhancer. Furthermore, we show that vsx2 knockdown impairs the primary optic cup
      folding. These data support a model by which vsx2, operating through the effector
      gene opo, acts as a central transcriptional node that coordinates neural retina
      patterning and optic cup invagination in zebrafish. 

PMID- 25963170
TI  - Contemporary Imaging Practice Patterns Following Ureteroscopy for Stone Disease.
AB  - BACKGROUND AND PURPOSE: Routine imaging following ureteroscopy for treatment of
      renal/ureteral calculi continues to be a topic of debate. However, with the
      increasing focus on healthcare costs and quality, judicious use of diagnostic
      imaging to optimize outcomes while minimizing resource utilization is a priority.
      We sought to identify post-ureteroscopy imaging practices among experienced
      urologists. MATERIALS AND METHODS: A REDcap questionnaire was sent to urologists
      in North America. The questionnaire surveyed demographic data, clinical volume,
      and imaging preferences post-ureteroscopy. Additionally, we surveyed the extent
      to which stone, anatomic, and procedure-related factors influenced these
      preferences. The likelihood of altering clinical practice and the desire for
      specific imaging guidelines were also assessed. The interquartile range (IQR) was
      utilized as a measure of median consensus. RESULTS: Three hundred twenty-two
      urologists completed the questionnaire. The mean number of years in practice was
      18 +/- 10; 82% of respondents performed more than five ureteroscopic stone
      procedures monthly. Routine postoperative imaging was obtained by 48% of
      participants as follows: ultrasound (US) (47%), kidneys, ureters, and bladder
      (KUB) (17%), CT (4%), intravenous pyelogram (IVP) (2%), and KUB+US (30%).
      Urologists who did not routinely image patients were more concerned about cost
      (55% vs 25%, p <= 0.0001), radiation exposure (69% vs 44%, p <= 0.0001), and
      diagnostic inaccuracy of US (57% vs 44%, p <= 0.02). These urologists were also
      less likely to have completed an endourology fellowship (7% vs 23%, p <= 0.0001).
      The most compelling predictors of obtaining postoperative imaging were
      postoperative pain and fever (median 5, IQR 1), residual stones (median 5, IQR
      1), ureteral perforation (median 5, IQR 2), and presence of a solitary kidney
      (median 4.5, IQR 2). CONCLUSIONS: Currently, about 50% of urologists who
      regularly perform ureteroscopic stone procedures obtain postoperative imaging.
      Imaging preferences were guided by the presence of residual fragments, ureteral
      perforation, solitary kidney, and postoperative pain or fever.

PMID- 25963171
TI  - [Sudden cardiac death in athletes and its prevention].
AB  - Athletes and especially elite athletes are predominantly young people and are not
      associated with high health risks, apart from traumatic injuries. Nevertheless,
      there is a significantly high incidence of sudden cardiac death (SCD), which
      ranges from 0.6 to 3.0/100,000 athletes per year. Often the SCD is the first
      manifestation of an underlying cardiac disease. Distinct structural cardiac
      disorders, such as hypertrophic cardiomyopathy, coronary artery anomalies (17 %),
      inflammatory disorders (6 %) and arrhythmogenic right ventricular cardiomyopathy
      as well as conditions without structural cardiac abnormalities, such as primary
      electrical diseases (channelopathies) are important causes of sudden death. A
      simple screening can help to identify athletes with these diseases and allow
      specific therapies or precautionary measures to be initiated.

PMID- 25963172
TI  - Sports in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy
      and desmosomal mutations.
AB  - Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a rare
      cardiomyopathy associated with life-threatening arrhythmias and an increased risk
      of sudden cardiac death. In addition to mutations in desmosomal genes,
      environmental factors such as exercise and sport have been implicated in the
      pathogenesis of the disease. Recent studies have shown that exercise may be
      associated with adverse outcomes in patients with ARVD/C. On the basis of current
      evidence, patients with ARVD/C are recommended to limit exercise irrespective of
      their mutation status. Some studies have suggested the presence of an entirely
      acquired form of the disease caused by exercise, which has been dubbed "exercise
      induced ARVD/C." 

PMID- 25963173
TI  - [Pulmonary hypertension: Possible genetic causes and therapeutic options].
AB  - Pulmonary hypertension (PH) is a severe disease, which is usually only recognized
      at a late stage. It is characterized by dyspnea and right heart insufficiency. In
      some forms of pulmonary hypertension, such as the rare pulmonary arterial
      hypertension (PAH) and PAH associated with congenital heart defects, genetic
      factors have been identified. This article summarizes the general and supportive
      therapies for PH, targeted pharmaceutical treatment for PAH and non-operable
      chronic thromboembolic pulmonary hypertension. To achieve acceptable survival
      rates, it is essential to transfer patients to an expert center at an early stage
      for further differential diagnostics and therapy. 

PMID- 25963174
TI  - Oxidative Olefination of Anilides with Unactivated Alkenes Catalyzed by an
      (Electron-Deficient eta(5) -Cyclopentadienyl)Rhodium(III) Complex Under Ambient
      Conditions.
AB  - The oxidative olefination of sp(2) C-H bonds of anilides with both activated and
      unactivated alkenes using an (electron-deficient eta(5) 
      cyclopentadienyl)rhodium(III) complex is reported. In contrast to reactions using
      this electron-deficient rhodium(III) catalyst, [Cp*RhCl2 ]2 showed no activity
      against olefination with unactivated alkenes. In addition, the deuterium kinetic
      isotope effect (DKIE) study revealed that the C-H bond cleavage step is thought
      to be the turnover-limiting step.

PMID- 25963175
TI  - Design, testing, and scale-up of medical devices for global health: negative
      pressure wound therapy and non-surgical male circumcision in Rwanda.

PMID- 25963176
TI  - Provider-Level Characteristics Associated With Adolescent Varicella,
      Meningococcal, and Human Papillomavirus Immunization Initiation.
AB  - PURPOSE: We examined patient- and provider-level factors associated with
      initiation of three adolescent immunizations among 13 to 18 year olds in an
      adolescent primary care clinic. METHODS: Data were extracted retrospectively from
      medical records. Logistic regression models identified associations with
      immunization initiation. Post hoc analyses stratified by gender were conducted to
      examine provider-type contribution to human papillomavirus (HPV) immunization
      initiation. RESULTS: Among 2932 adolescents, rates of meningococcal and varicella
      immunization initiation differed by age. Girls were more likely to have initiated
      HPV immunization than boys. The probability of girls initiating HPV immunization
      was the same when last seen by advanced practice nurses (APNs) versus physicians,
      but the probability of boys initiating HPV immunization was lower when last seen
      by APNs. CONCLUSIONS: Differences in HPV immunization initiation were observed
      between genders, and for boys, between APN versus physician at last clinic visit.
      This may reflect changes to HPV immunization recommendations for boys and APNs
      having shorter clinic visits.

PMID- 25963177
TI  - Factors Affecting Care in Non-English-Speaking Patients and Families.
AB  - OBJECTIVE: Identify concerns in non-English-speaking patients to improve patient
      care and communication. Misunderstandings due to language barriers can impose
      undue hardship possibly leading to adverse outcomes. Information from this study
      may identify ways of improving care. METHODS: A 31-question survey was
      administered in the patients' native language using certified medical
      interpreters. Surveys were collected anonymously during clinic visits. RESULTS:
      Thirty-eight surveys were completed and compiled. Most were happy with their
      provider. Half indicated that they did not know why they were seeing that
      provider, did not understand the tests, or had difficulty with interpreters. Many
      indicated they would like medical information written in their native language.
      CONCLUSION: Barriers to communication can lead to adverse medical outcomes, poor
      compliance with therapy, and poor understanding of medical conditions. Providing
      written information in the patient's native language has the potential to
      complement the verbal discussion and enhance patient care.

PMID- 25963178
TI  - Dissemination of Evidence-Based Behavioral Advice via Video in Pediatric Primary
      Care: An Acceptance and Utilization Study.
AB  - BACKGROUND: Research suggests that multimedia-based interventions possess
      advantages for disseminating safe and effective methods of behavior management to
      parents in pediatric primary care; however, little is known about their
      utilization in real-life settings. In order to maximize the impact of multimedia
      resources, more knowledge regarding dissemination and implementation is needed.
      OBJECTIVE: To examine provider and parental perception and utilization of videos
      designed to communicate evidence-based parenting strategies for disruptive
      behavior. Videos were available in clinic and online. RESULTS: Both provider and
      parent perceptions of the videos were largely positive. However, of 240 parents
      surveyed, only 33% were aware of the availability of videos subsequent to a well
      child visit. Parents were unlikely to view the videos if they did not do so as
      part of their child's health care visit. CONCLUSION: Multimedia interventions for
      behavior management are likely to be well received, but systematic methods of
      implementation are needed. Further study of dissemination of multimedia
      interventions is merited.

PMID- 25963179
TI  - HIT or Miss: The Sequential Diagnostic Approach to Heparin-Induced
      Thrombocytopenia Illustrated in a Child With Acute Post-Streptococcal
      Glomerulonephritis.

PMID- 25963180
TI  - Eight-Month-Old Male With Four Days of Increased Work of Breathing.

PMID- 25963181
TI  - Serotype 35B Pneumococcal Meningitis in an Infant: Effect of Conjugate Vaccines
      on Invasive Disease and Implications for Practice.

PMID- 25963183
TI  - The Artificial Urinary Sphincter is Superior to a Secondary Transobturator Male
      Sling in Cases of a Primary Sling Failure.
AB  - PURPOSE: We compared continence outcomes in patients with post-prostatectomy
      stress urinary incontinence treated with a salvage artificial urinary sphincter
      vs a secondary transobturator sling. MATERIALS AND METHODS: We retrospectively
      reviewed the records of patients undergoing salvage procedures after sling
      failure from 2006 to 2012. Postoperative success was defined as the use of 0 or 1
      pad, a negative stress test and pad weight less than 8 gm per day. We performed
      the Wilcoxon test and used a Cox regression model and Kaplan-Meier survival
      analysis. RESULTS: A total of 61 men presenting with sling failure were included
      in study, of whom 32 went directly to an artificial urinary sphincter and 29
      received a secondary sling. Of the artificial urinary sphincter cohort 47%
      underwent prior external beam radiation therapy vs 17% of the secondary sling
      cohort (p = 0.01). Average preoperative 24 hour pad weight and pad number were
      higher in the artificial urinary sphincter cohort. Median followup in artificial
      urinary sphincter and secondary sling cases was 4.5 (IQR 4-12) and 4 months (IQR
      1-5), respectively. Overall treatment failure was seen in 55% of patients (16 of
      29) with a secondary sling vs 6% (2 of 32) with an artificial urinary sphincter
      (unadjusted HR 7, 95% CI 2-32 and adjusted HR 6, 95% CI 1-31). CONCLUSION: In
      this cohort of patients with post-prostatectomy stress urinary incontinence and a
      failed primary sling those who underwent a secondary sling procedure were up to 6
      times more likely to have persistent incontinence vs those who underwent
      artificial urinary sphincter placement. These data are useful for counseling
      patients and planning surgery. We currently recommend placement of an artificial
      urinary sphincter for patients in whom an initial sling has failed.

PMID- 25963184
TI  - Uroepithelial Thickening on Sonography Improves Detection of Vesicoureteral
      Reflux in Children with First Febrile Urinary Tract Infection.
AB  - PURPOSE: The 2011 American Academy of Pediatrics clinical practice guideline for
      childhood febrile urinary tract infection recommends voiding cystourethrography
      if renal and bladder ultrasound reveals hydronephrosis, scarring or "other
      findings" that suggest high grade vesicoureteral reflux. We sought to determine
      if the finding of uroepithelial thickening indicates greater risk of high grade
      vesicoureteral reflux and whether uroepithelial thickening improves the screening
      value of renal and bladder ultrasound. MATERIALS AND METHODS: We retrospectively
      analyzed renal and bladder ultrasound and voiding cystourethrogram findings in
      children 2 to 24 months old with first febrile urinary tract infection during an
      11-year period. Patients with uroepithelial thickening were compared to an age
      and gender matched sample without uroepithelial thickening. Logistic regression
      was used to identify factors associated with high grade vesicoureteral reflux.
      Test characteristics of renal and bladder ultrasound for high grade reflux were
      compared based on different criteria to define an abnormal renal and bladder
      ultrasound. RESULTS: Of 226 patients 143 (63%) had vesicoureteral reflux, of whom
      37 (26%) had high grade reflux. On multivariable analysis uroepithelial
      thickening was a significant independent predictor of high grade vesicoureteral
      reflux (OR 5.41, 95% CI 1.74-16.79, p = 0.004). When hydronephrosis and
      hydroureter were considered the only abnormal renal and bladder ultrasound
      findings warranting voiding cystourethrography, sensitivity of renal and bladder
      ultrasound for high grade reflux was 84%, and 6 children with high grade and 82
      with low grade reflux would have been missed. When uroepithelial thickening was
      also considered an abnormal finding, the sensitivity increased to 97%, and only 1
      child with high grade and 57 with low grade reflux would have been missed.
      CONCLUSIONS: Uroepithelial thickening is associated with an increased risk of
      high grade vesicoureteral reflux and is an abnormal finding warranting voiding
      cystourethrography. Sensitivity of renal and bladder ultrasound as a screening
      test for high grade vesicoureteral reflux is markedly improved when uroepithelial
      thickening is considered.

PMID- 25963182
TI  - Sural-sparing in Guillain-Barre syndrome: Does it mean lack of histopathological
      changes?

PMID- 25963186
TI  - Transperineal Template Guided Prostate Biopsy Selects Candidates for Active
      Surveillance--How Many Cores are Enough?
AB  - PURPOSE: Most prostate cancer active surveillance protocols recommend a
      confirmatory biopsy within 3 to 6 months of diagnosis. Transperineal template
      guided biopsy is an approach to improve the detection of high grade prostate
      cancer. However, to our knowledge the optimal technique is unknown. We evaluated
      the relative performance of 2 transperineal template guided biopsy approaches.
      MATERIALS AND METHODS: Institutional review board approved prospective databases
      at Virginia Mason and University of Michigan were used. Men eligible for active
      surveillance based on initial 12-core biopsy demonstrating NCCN(r) guideline low
      risk prostate cancer were included in study. All men underwent confirmatory
      transperineal template guided biopsy between 2005 and 2014, and within 6 months
      of diagnosis. The biopsy technique was based on a 24-core template with 12
      anterior and 12 posterior cores or a template based on gland volume with an
      average of 1 core per cc. Outcome comparisons were made by the chi-square and
      Fisher exact tests, the Welch t-test and linear regression. RESULTS: Of the 135
      men 46 underwent 24-core biopsy and 89 underwent volume based biopsy (median 62
      cores). No statistically significant difference was noted in the prevalence of
      upgrading (35% vs 29%, p = 0.64) or complications (9% vs 16%, p = 0.38) between
      the 24-core and volume based groups. The difference in the probability of
      upgrading by volume based biopsy adjusted for age, prostate specific antigen,
      prostate volume, clinical stage and number of prior biopsies was -4% (95% CI -24
      to 14%, p = 0.63). CONCLUSIONS: A significant difference was not detected in
      upgrading or morbidity between a 24-core template and a more exhaustive volume
      based template. A less invasive 24-core transperineal template guided biopsy
      strategy may suffice to accurately identify men who are appropriate for active
      surveillance.

PMID- 25963185
TI  - Effects of Chronic Pelvic Pain on Heart Rate Variability in Women.
AB  - PURPOSE: Interstitial cystitis/bladder pain syndrome and myofascial pelvic pain
      are frequently comorbid chronic pelvic pain disorders. Differences in bladder
      function between interstitial cystitis/bladder pain syndrome and myofascial
      pelvic pain suggest that efferent autonomic function may differentiate these
      syndromes. Heart rate variability, defined as the difference in duration of
      successive heartbeats, serves as an index of autonomic function by measuring its
      ability to modify heart rate in response to neurophysiological changes. High
      frequency heart rate variability was used as a reflection of more rapid vagally
      mediated (parasympathetic) changes. Low frequency heart rate variability
      signified slower fluctuations related to the baroreflex and sympathetic outflow.
      MATERIALS AND METHODS: Heart rate variability was derived by autoregressive
      frequency analysis of the continuous electrocardiogram recording of heart rate
      with the subject supine for 10 minutes, tilted 70 degrees with the head up for 30
      minutes and supine again for 10 minutes. This institutional review board approved
      study included 105 female subjects, including 32 who were healthy, and 26 with
      interstitial cystitis/bladder pain syndrome, 12 with myofascial pelvic pain and
      35 with interstitial cystitis/bladder pain syndrome plus myofascial pelvic pain.
      RESULTS: In all positions healthy controls had higher high frequency heart rate
      variability than women with interstitial cystitis/bladder pain syndrome and
      interstitial cystitis/bladder pain syndrome plus myofascial pelvic pain. Subjects
      with myofascial pelvic pain were similar to controls with greater high frequency
      heart rate variability at baseline (supine 1) and in upright positions than
      subjects with interstitial cystitis/bladder pain syndrome. Differences in low
      frequency heart rate variability were less evident while low-to-high frequency
      ratio differences appeared to be driven by the high frequency heart rate
      variability component. CONCLUSIONS: Subjects with interstitial cystitis/bladder
      pain syndrome had diminished vagal activity and a shift toward sympathetic
      nervous system dominance. Overall these data support the hypothesis that changes
      in autonomic function occur in interstitial cystitis/bladder pain syndrome but
      not in myofascial pelvic pain. These changes may result from interstitial
      cystitis/bladder pain syndrome or contribute to its pathophysiology through
      abnormal self-regulatory function.

PMID- 25963187
TI  - Novel Strategy for Temporary Decompression of the Lower Urinary Tract in Neonates
      Using a Ureteral Stent.
AB  - PURPOSE: In children with congenital obstructive uropathy, including posterior
      urethral valves, lower urinary tract decompression is recommended pending
      definitive surgical intervention. Current options, which are limited to a feeding
      tube or Foley catheter, pose unappreciated constraints in luminal diameter and
      are associated with potential problems. We assess the impact of luminal diameter
      on the current draining options and present a novel alternative method,
      repurposing a widely available stent that optimizes drainage. MATERIALS AND
      METHODS: We retrospectively reviewed patients diagnosed with posterior urethral
      valves between January 2013 and December 2014. In all patients a 6Fr 12 cm Double
      J ureteral stent was advanced over a guidewire in a retrograde fashion into the
      bladder. Luminal flow and cross-sectional areas were also assessed for each of 3
      tubes for urinary drainage, ie 6Fr Double-J stent, 5Fr feeding tube and 6Fr Foley
      catheter. RESULTS: A total of 30 patients underwent uneventful bedside Double-J
      stent placement. Mean +/- SD age at valve ablation was 28.5 +/- 16.6 days. Mean
      +/- SD peak serum creatinine was 2.23 +/- 0.97 mg/dl after birth and 0.56 +/-
      0.22 mg/dl at the procedure. Urine output after stent placement was excellent in
      all patients. The Foley catheter and feeding tube drained approximately 18 and 6
      times more slowly, respectively, and exhibited half the calculated cross
      sectional luminal area compared to the Double-J stent. CONCLUSIONS: Use of Double
      J stents in neonates with posterior urethral valves is a safe and effective
      alternative method for lower urinary tract decompression that optimizes the
      flow/lumen relationship compared to conventional drainage options.

PMID- 25963189
TI  - Predictive Factors for Spontaneous Stone Passage and the Potential Role of Serum
      C-Reactive Protein in Patients with 4 to 10 mm Distal Ureteral Stones: A
      Prospective Clinical Study.
AB  - PURPOSE: We investigated possible predictive factors for spontaneous stone
      passage and the potential role of serum C-reactive protein and white blood count
      in patients with 4 to 10 mm distal ureteral stones. MATERIALS AND METHODS: A
      total of 251 patients who presented with renal colic secondary to distal ureteral
      stone were included in study. Patients were grouped according to spontaneous
      stone passage. Serum C-reactive protein, white blood count and other possible
      factors were investigated for their potential predictive value for spontaneous
      stone passage at a followup of 5 weeks. Potential predictive factors for
      spontaneous stone passage were evaluated with univariate and multivariate
      analyses. ROC curve analysis was performed to find an optimal cutoff value for
      serum C-reactive protein according to spontaneous stone passage. Statistical
      significance was considered at p <0.05. RESULTS: Spontaneous stone passage was
      observed in 135 patients (53.8%) in group 1 while 116 (46.2%) in group 2 did not
      expel the stone spontaneously. Median stone size was 5.7 mm. Stone size, serum C
      reactive protein and white blood count were significantly higher in group 2 than
      in group 1. The number of patients with hydronephrosis and the number with
      spontaneous stone passage history were significantly lower in group 2 compared to
      group 1. The cutoff value of serum C-reactive protein provided by ROC analysis
      was 0.506 mg/l. Time to spontaneous stone passage was significantly higher in
      patients with serum C-reactive protein above the threshold and in patients with
      ureteral stones greater than 6 mm. CONCLUSIONS: Stone size, previous spontaneous
      passage, hydronephrosis, serum C-reactive protein and white blood count can be
      used to predict spontaneous stone passage in patients with 4 to 10 mm distal
      ureteral stones. A serum C-reactive protein level of 0.506 mg/l can serve as a
      cutoff value to predict spontaneous stone passage.

PMID- 25963188
TI  - Management of Proximal Hypospadias with 2-Stage Repair: 20-Year Experience.
AB  - PURPOSE: We describe our experience with 2-stage proximal hypospadias repair. We
      report outcomes, and patient and procedure characteristics associated with
      surgical complications. MATERIALS AND METHODS: We retrospectively studied
      patients with proximal hypospadias who underwent staged repair between January
      1993 and December 2012. Demographics, preoperative management and operative
      technique were reviewed. Complications included glans dehiscence, fistula, meatal
      stenosis, nonmeatal stricture, urethrocele/diverticula and residual chordee. Cox
      proportional hazards model was used to evaluate the associations between time to
      surgery for complications and patient and procedure level factors. RESULTS: A
      total of 134 patients were included. Median patient age was 8.8 months at first
      stage surgery and 17.1 months at second stage surgery, and median time between
      surgeries was 8 months. Median followup was 3.8 years. Complications were seen in
      71 patients (53%), with the most common being fistula (39 patients, 29.1%).
      Reoperation was performed in 66 patients (49%). Median time from urethroplasty to
      surgery for complication was 14.9 months. Use of preoperative testosterone
      decreased risk of undergoing surgery for complication by 27% (HR 0.73, 95% CI
      0.55-0.98, p = 0.04). In addition, patients identified as Hispanic were at
      increased risk for undergoing surgery for complications (HR 2.40, 95% CI 1.28
      4.53, p = 0.01). CONCLUSIONS: We review the largest cohort of patients undergoing
      2-stage hypospadias repair at a single institution. Complications and reoperation
      rates were approximately 50% in the setting of complex genital reconstruction.

PMID- 25963190
TI  - Management of Node Only Recurrence after Primary Local Treatment for Prostate
      Cancer: A Systematic Review of the Literature.
AB  - PURPOSE: We analyzed all available studies assessing the management of node only
      recurrence after primary local treatment of prostate cancer. MATERIALS AND
      METHODS: We systematically reviewed the literature in January 2015 using the
      PubMed, Web of Sciences and Embase databases according to PRISMA guidelines.
      Studies exclusively reporting visceral or bone metastatic disease were excluded
      from analysis. Eight radiotherapy and 12 salvage lymph node dissection series
      were included in our qualitative study. RESULTS: All 248 radiotherapy and 480
      salvage lymph node dissection studies were single arm case series including a
      total of 728 patients. Choline positron emission tomography/computerized
      tomography was the reference imaging technique for nodal recurrence detection.
      Globally 50% of patients remained disease-free after short-term followup.
      Nevertheless, approximately two-thirds of patients received adjuvant hormone
      therapy, leading an overestimation of prostate specific antigen-free survival
      rates obtained after salvage treatment. Combining radiotherapy with salvage lymph
      node dissection may improve oncologic control in the treated region without
      improving the outfield relapse risk or the prostate specific antigen response.
      Great heterogeneity among series in adjuvant treatments, endpoints, progression
      definitions and study populations made it difficult to assess the precise impact
      of salvage treatment on the prostate specific antigen response and compare
      outcomes between radiotherapy and salvage lymph node dissection series. Toxicity
      after radiotherapy or salvage lymph node dissection was acceptable without
      frequent high grade complications. The benefit of early hormone therapy as the
      only salvage treatment remains unknown. CONCLUSIONS: Although a high level of
      evidence is currently missing to draw any strong conclusion, published clinical
      series show that in select patients salvage treatment directed to nodal
      recurrence could lead to good oncologic outcomes. Although the optimal timing of
      androgen deprivation therapy in this setting is still unknown, such an approach
      could delay time to systemic treatment with an acceptable safety profile. Future
      prospective trials are awaited to better clarify this potential impact on well
      defined endpoints.

PMID- 25963191
TI  - A Review of the Use of Iloprost, A Synthetic Prostacyclin, in the Prevention of
      Radiocontrast Nephropathy in Patients Undergoing Coronary Angiography and
      Intervention.
AB  - Iloprost, a prostacyclin analogue, has been effective in preventing renal
      dysfunction among transplant patients. We hypothesized that iloprost is
      protective against renal dysfunction in different settings, in which similar
      underlying mechanisms of nephrotoxicity occur. We conducted a literature review,
      and discuss the application of iloprost in reducing acute renal insufficiency and
      the pathophysiological mechanisms of contrast-induced nephropathy (CIN). One
      proposed mechanism of CIN is prolonged renal arterial vasoconstriction, causing
      renal hypoperfusion, ischemia, and release of free radicals. Iloprost is an
      analogue of the vasodilatory prostaglandin PGI2 . It has demonstrated
      cytoprotective properties in the renal transplant population by inhibiting
      lysosomal degradation and release of free radicals, allowing membrane
      stabilization. Two good-quality studies reported on iloprost and CIN. Five
      studies reported protective effects of iloprost in renal transplantation and 1 in
      coronary artery bypass grafting. Iloprost was found to be renoprotective in
      patients with baseline renal insufficiency who underwent coronary angiography for
      CIN (risk ratio [RR] = 0.32, 95% confidence interval [CI]: 0.16-0.67) and
      increases the weighted mean difference improvement in creatinine clearance (RR =
      4.56, 95% CI: 1.82-7.30). CIN is associated with major adverse cardiac events.
      Preventing CIN is important for patient safety and reducing disease burden.
      Iloprost may reduce CIN by up to 68%. The same mechanisms of iloprost that
      inhibit graft dysfunction in the acute post-renal transplant and cardiopulmonary
      bypass setting may also contribute to preventing CIN. Large randomized controlled
      trials are necessary to determine the clinical efficacy of iloprost in the
      angiography setting. 

PMID- 25963192
TI  - CD-200 induces apoptosis and inhibits Bcr-Abl signaling in imatinib-resistant
      chronic myeloid leukemia with T315I mutation.
AB  - Chronic myeloid leukemia (CML) is characterized by a constitutively active Bcr
      Abl tyrosine kinase. Although Imatinib has been proven to be an effective drug
      against CML, its resistance has been observed with disease relapse due to T315I
      predominant point mutation. Liriodendron tulipifera L., one of the fastest
      growing hardwood tree species, exerts antioxidant activity and anti-inflammatory
      effects. However, its anticancer effect has been minimally reported. In this
      study, we extracted CD-200 from Liriodendron tulipifera L. and investigated its
      effect on cell survival or apoptosis in CML cells with Bcr-Abl/T315I (BaF3/T315I)
      as well as wild-type Bcr-Abl (BaF3/WT). CD-200 inhibited cell proliferation in
      the BaF3/WT cells, and also in the BaF3/T315I cells with Imatinib resistance.
      Moreover, it strongly inhibited Bcr-Abl signaling pathways in a dose-dependent
      manner. Also, it significantly increased the sub-G1 phase and the expression of
      cleaved PARP and caspase-3, as well as the TUNEL-positive apoptotic cells. In
      addition, we observed that CD-200 induced apoptosis with a loss of mitochondrial
      membrane potential by decreasing the expression of Mcl-1 and survivin.
      Furthermore, CD-200 showed a significant inhibition in tumor growth, compared to
      Imatinib in BaF3/T315I mouse xenograft models. Taken together, our study
      demonstrates that CD-200 exhibits apoptosis induction and anti-proliferative
      effect by blocking the Bcr-Abl signaling pathways in the Bcr-Abl/T315I with
      resistance to Imatinib. We suggest that CD-200 may be a natural product to target
      Bcr-Abl and overcome Imatinib resistance in CML patients.

PMID- 25963193
TI  - Metabolic syndrome is associated with better prognosis in patients with tongue
      squamous cell carcinoma.
AB  - INTRODUCTION: Metabolic syndrome (MS) is associated with several cancers, but it
      is not clear whether MS affects the prognosis of tongue squamous cell carcinoma
      (TSCC). This study aimed to evaluate the prognostic value of MS in TSCC. METHODS:
      Clinical data from 252 patients with TSCC who were initially treated at the Sun
      Yat-sen University Cancer Center between April 1998 and June 2011 were collected,
      and the associations between MS and clinicopathologic factors were
      retrospectively analyzed. Prognostic outcomes were examined by Kaplan-Meier
      analysis and Cox regression analysis. RESULTS: Of the 252 patients, 48 were
      diagnosed with MS. MS was associated with early N category in TSCC (P < 0.001).
      The patients with MS showed longer survival than those without MS (P = 0.028). MS
      was an independent prognostic factor for patients with TSCC. CONCLUSIONS: MS is
      associated with early N category in TSCC. It is an independent prognostic factor
      for better survival in patients with TSCC.

PMID- 25963194
TI  - Evolving "creature": an avoidable oxymoron.

PMID- 25963195
TI  - Dual embryonic origin and patterning of the pharyngeal skeleton in the axolotl
      (Ambystoma mexicanum).
AB  - The impressive morphological diversification of vertebrates was achieved in part
      by innovation and modification of the pharyngeal skeleton. Extensive fate mapping
      in amniote models has revealed a primarily cranial neural crest derivation of the
      pharyngeal skeleton. Although comparable fate maps of amphibians produced over
      several decades have failed to document a neural crest derivation of ventromedial
      elements in these vertebrates, a recent report provides evidence of a mesodermal
      origin of one of these elements, basibranchial 2, in the axolotl. We used a
      transgenic labeling protocol and grafts of labeled cells between GFP+ and white
      embryos to derive a fate map that describes contributions of both cranial neural
      crest and mesoderm to the axolotl pharyngeal skeleton, and we conducted
      additional experiments that probe the mechanisms that underlie mesodermal
      patterning. Our fate map confirms a dual embryonic origin of the pharyngeal
      skeleton in urodeles, including derivation of basibranchial 2 from mesoderm
      closely associated with the second heart field. Additionally, heterotopic
      transplantation experiments reveal lineage restriction of mesodermal cells that
      contribute to pharyngeal cartilage. The mesoderm-derived component of the
      pharyngeal skeleton appears to be particularly sensitive to retinoic acid (RA):
      administration of exogenous RA leads to loss of the second basibranchial, but not
      the first. Neural crest was undoubtedly critical in the evolution of the
      vertebrate pharyngeal skeleton, but mesoderm may have played a central role in
      forming ventromedial elements, in particular. When and how many times during
      vertebrate phylogeny a mesodermal contribution to the pharyngeal skeleton evolved
      remain to be resolved. 

PMID- 25963196
TI  - Nuclear beta-catenin localization supports homology of feathers, avian scutate
      scales, and alligator scales in early development.
AB  - Feathers are an evolutionary novelty found in all extant birds. Despite recent
      progress investigating feather development and a revolution in dinosaur
      paleontology, the relationship of feathers to other amniote skin appendages,
      particularly reptile scales, remains unclear. Disagreement arises primarily from
      the observation that feathers and avian scutate scales exhibit an anatomical
      placode-defined as an epidermal thickening-in early development, whereas
      alligator and other avian scales do not. To investigate the homology of feathers
      and archosaur scales we examined patterns of nuclear beta-catenin localization
      during early development of feathers and different bird and alligator scales. In
      birds, nuclear beta-catenin is first localized to the feather placode, and then
      exhibits a dynamic pattern of localization in both epidermis and dermis of the
      feather bud. We found that asymmetric avian scutate scales and alligator scales
      share similar patterns of nuclear beta-catenin localization with feathers. This
      supports the hypothesis that feathers, scutate scales, and alligator scales are
      homologous during early developmental stages, and are derived from early
      developmental stages of an asymmetric scale present in the archosaur ancestor.
      Furthermore, given that the earliest stage of beta-catenin localization in
      feathers and archosaur scales is also found in placodes of several mammalian skin
      appendages, including hair and mammary glands, we hypothesize that a common skin
      appendage placode originated in the common ancestor of all amniotes. We suggest a
      skin placode should not be defined by anatomical features, but as a local,
      organized molecular signaling center from which an epidermal appendage develops. 

PMID- 25963197
TI  - Another biomineralising protostome with an msp130 gene and conservation of msp130
      gene structure across Bilateria.
AB  - Msp130 genes are known for their association with biomineralisation, principally
      in echinoderm skeletogenesis. Recently, msp130 genes were shown to exist more
      widely across the animal kingdom, including in molluscs, and a hypothesis was
      formed that the genes had arisen independently in the deuterostome and mollusc
      lineages via horizontal gene transfer, thus facilitating the evolution of
      biomineralisation in these distinct lineages (Ettensohn, 2014). Here we show that
      another biomineralising protostome, the polychaete Spirobranchus (formerly
      Pomatoceros) lamarcki also possesses an msp130 gene, and expresses it during a
      biomineralisation process. However, based on analysis of gene structure, we
      hypothesize that the protostome and deuterostome msp130 genes did not originate
      from independent horizontal gene transfers, but instead are descended from a gene
      already present in the bilaterian ancestor, with the gene being secondarily lost
      from several lineages. 

PMID- 25963199
TI  - Immediate versus Delayed Treatment in the Anterior Maxilla Using Single Implants
      with a Laser-Microtextured Collar: 3-Year Results of a Case Series on Hard- and
      Soft-Tissue Response and Esthetics.
AB  - PURPOSE: To compare peri-implant marginal bone loss, soft tissue response, and
      esthetics following single immediate implant treatment (IIT) and delayed implant
      treatment (DIT) in the esthetic zone of the maxilla in well-selected patients.
      MATERIALS AND METHODS: Adequate bone volume and ideal soft tissue level/contour
      were considered requirements for implant therapy, with additional prerequisites
      for IIT of residual alveolar bone wall integrity and a thick gingival biotype.
      IIT included immediate placement and provisionalization, while DIT included
      extraction socket preservation followed by implant placement and
      provisionalization 4 months later. Cortical bone levels and peri-implant mucosal
      conditions were evaluated at regular intervals. The esthetic outcome was
      objectively rated after 3 years using the pink esthetic score (PES) and white
      esthetic score (WES). RESULTS: Twelve patients received an immediate Laser-Lok(r)
      implant, and 13 patients received a delayed Laser-Lok(r) implant. No significant
      differences were found between the study groups regarding survival rate (100%).
      The mean bone level from the implant/abutment interface was 0.35 +/- 0.18 mm for
      IIT and 0.42 +/- 0.21 mm for DIT after 3 years (p > 0.05). Mesial and distal
      papillae remained stable over time in DIT. A tendency for regrowth of mesial and
      distal papillae was found following IIT (p < 0.05). Midfacial soft tissues
      remained stable over time following DIT and IIT. CONCLUSIONS: Within the
      limitations of this study (e.g., small sample size, short follow-up duration),
      the results suggest that regarding success rate, hard/soft tissue responses, and
      esthetics, DIT and IIT with single Laser-Lok(r) implants in the anterior maxilla
      are comparable and predictable options for well-selected patients.

PMID- 25963198
TI  - The significance and scope of evolutionary developmental biology: a vision for
      the 21st century.
AB  - Evolutionary developmental biology (evo-devo) has undergone dramatic
      transformations since its emergence as a distinct discipline. This paper aims to
      highlight the scope, power, and future promise of evo-devo to transform and unify
      diverse aspects of biology. We articulate key questions at the core of eleven
      biological disciplines-from Evolution, Development, Paleontology, and
      Neurobiology to Cellular and Molecular Biology, Quantitative Genetics, Human
      Diseases, Ecology, Agriculture and Science Education, and lastly, Evolutionary
      Developmental Biology itself-and discuss why evo-devo is uniquely situated to
      substantially improve our ability to find meaningful answers to these fundamental
      questions. We posit that the tools, concepts, and ways of thinking developed by
      evo-devo have profound potential to advance, integrate, and unify biological
      sciences as well as inform policy decisions and illuminate science education. We
      look to the next generation of evolutionary developmental biologists to help
      shape this process as we confront the scientific challenges of the 21st century. 

PMID- 25963200
TI  - A hand hygiene compliance check system: brief communication on a system to
      improve hand hygiene compliance in hospitals and reduce infection.
AB  - Hand hygiene compliance is the most significant, modifiable cause of hospital
      acquired infections, yet national averages for compliance rates remain
      unsatisfactory. Noncompliance can contribute to patient mortality, extended
      hospital stays, higher re-admission rates, and lower reimbursement for hospitals
      under the Patient Protection and Affordable Care Act. Although several hand
      sanitizing tracking systems currently exist, they pose problems of personal
      tracking, workflow interference, system maintenance concerns, among others.
      Considering these barriers, we created a prototype system that includes
      compliance rate tracking, real-time sanitization reminders, and a data archive
      for future studies. 

PMID- 25963201
TI  - Trials are meaningful for clinical decision making only when their endpoints are
      valid and comparable.

PMID- 25963202
TI  - Patient-reported outcome measures in psoriasis: assessing the assessments.

PMID- 25963203
TI  - Fatigue in psoriasis: mapping the wider picture.

PMID- 25963204
TI  - Typing of the enigmatic Propionibacterium acnes.

PMID- 25963205
TI  - Dermoscopy for melanoma: don't forget to take a photo.

PMID- 25963206
TI  - Facial ageing: how do we measure up?

PMID- 25963207
TI  - Can you whistle? Then I'll come: stem cells home to where they're needed.

PMID- 25963208
TI  - Lymphaticosclerosis: a new way of thinking about lymphatic vessel obstruction.

PMID- 25963209
TI  - The role of increased T helper cell 2 cytokine expression in skin weals of
      chronic spontaneous urticaria: are they always activating cytokines?

PMID- 25963210
TI  - Predicting adequate surgical margins for cutaneous squamous cell carcinoma with
      dermoscopy.

PMID- 25963211
TI  - A history of gallstones associated with increased risk of psoriasis in U.S.
      women.

PMID- 25963212
TI  - Emotional and mental health impact of morphoea demonstrated in adults.

PMID- 25963213
TI  - Facial looks: new insight in risk factors involved in looking old.

PMID- 25963214
TI  - Prognostic parameters in Henoch-Schonlein purpura.

PMID- 25963215
TI  - The potential of daylight-activated photodynamic therapy for treating localized
      forms of cutaneous leishmaniasis in resource-limited settings.

PMID- 25963216
TI  - Five-year follow-up of ustekinumab efficacy: the influence of dose modification.

PMID- 25963217
TI  - Oral tofacitinib for psoriasis: what happens with interrupted treatment?

PMID- 25963218
TI  - Review of the 94th Annual Meeting of the British Association of Dermatologists,
      Glasgow 2014.
AB  - This is a review of the 94th Annual Meeting of the British Association of
      Dermatologists, held in Glasgow from 1 to 3 July 2014. The conference covered
      some of the latest developments in the treatment of atopic dermatitis, psoriasis
      and cancer, a follow-up on the methylisothiazolinone contact allergy epidemic,
      advances in genetically inherited disorders and somatic mutations underlying
      birth marks. In addition, there was an international perspective on vitiligo,
      leprosy and HIV, and a session discussing the regulatory process behind
      pharmaceutical development. 

PMID- 25963222
TI  - Contemporary cardiovascular device clinical trials (trends and patterns 2001 to
      2012).
AB  - Device uptake and development have progressed over the last decade, but few
      quantitative data exist examining the overall operating characteristics and
      temporal trends of these clinical trials. We performed a systematic analysis of
      all cardiovascular device clinical trials from 2001 to 2012 published in medical
      and cardiovascular journals with the 8 highest impact factors. Of the 1,224
      identified cardiovascular clinical trials, 299 (24.4%) focused specifically on
      devices. Each trial included a median of 335 patients (162 to 745) recruited from
      a median of 14 sites (3 to 38) over a median enrollment duration of 1.9 years
      (1.2 to 3.3). Median enrollment rate was 1.1 patients/site/month (0.5 to 4.2).
      Most device trials targeted coronary artery disease (55.2%), followed by
      arrhythmias (17.4%). Most were industry sponsored (53.6%) and included mortality
      as a primary end point (69.6%). The median number of patients (225 to 499, p
      <0.001 for trend) and enrolling sites (11 to 19, p = 0.07 for trend) increased
      from 2001 to 2012. During the study period, multinational enrollment grew and
      approached 50% (p = 0.03), whereas trials enrolling in North America exclusively
      decreased from 30% to 17% (p = 0.10 for trend). Approximately 70% of device
      trials met their primary end points; this rate did not significantly change over
      time. In conclusion, this descriptive study of the contemporary cardiovascular
      device clinical trials highlights recent trends toward larger, more international
      trial programs. These aggregate data may help inform future cardiovascular device
      development.

PMID- 25963221
TI  - Relation of frailty to outcomes after transcatheter aortic valve replacement
      (from the PARTNER trial).
AB  - Transcatheter aortic valve replacement (TAVR) is an effective treatment for
      severe symptomatic aortic stenosis (AS) in patients who are inoperable or at high
      risk for surgery. However, the intermediate- to long-term mortality is high,
      emphasizing the importance of patient selection. We, therefore, sought to
      evaluate the prognostic value of frailty in older recipients of TAVR,
      hypothesizing that frail patients would experience a higher mortality rate and a
      higher likelihood of poor outcome 1 year after TAVR. This substudy of the
      Placement of Aortic Transcatheter Valves trial was conducted at 3 high-enrolling
      sites where frailty was assessed systematically before TAVR. In total, 244
      patients received TAVR at the participating sites. Frailty was assessed using a
      composite of 4 markers (serum albumin, dominant handgrip strength, gait speed,
      and Katz activity of daily living survey), which were combined into a frailty
      score. The cohort was dichotomized at median frailty score. Outcomes measures
      were the time to death from any cause for >1 year of follow-up and poor outcome
      at 1 year. Poor outcome was defined as (1) death, (2) Kansas City Cardiomyopathy
      Questionnaire overall summary (KCCQ-OS) score <60, or (3) decrease of >=10 points
      in the KCCQ-OS score from baseline to 1 year. At 1 year, the Kaplan-Meier
      estimated all-cause mortality rate was 32.7% in the frail group and 15.9% in the
      nonfrail group (log-rank p = 0.004). At 1 year, poor outcome occurred in 50.0% of
      the frail group and 31.5% of the nonfrail group (p = 0.02). In conclusion,
      frailty was associated with increased mortality and a higher rate of poor outcome
      1 year after TAVR.

PMID- 25963223
TI  - Usefulness of an Echocardiographic Composite Cardiac Calcium Score to Predict
      Death in Patients With Stable Coronary Artery Disease (from the Heart and Soul
      Study).
AB  - Mitral annular calcium and aortic valve sclerosis on transthoracic
      echocardiography (TTE) are independently associated with cardiovascular (CV)
      events in patients with coronary artery disease (CAD). However, the prognostic
      value of calcific deposits at multiple sites is unknown. We performed TTEs in a
      prospective cohort of 595 outpatients with stable CAD and graded the severity of
      calcific deposition at 6 sites: mitral annulus, aortic valve, aortic ring,
      sinotubular junction, papillary muscle tip, and left main coronary artery. For
      each site with moderate calcific deposition or greater, 1 point was given to
      generate a composite cardiac calcium score (maximum of 6). The primary end point
      was the occurrence of CV events-a composite of death, myocardial infarction,
      stroke, transient ischemic attack, and heart failure. The association of the
      composite calcium score with CV events was evaluated using multivariate Cox
      proportional hazards models. Over a median follow-up of 4.2 years, 205 CV events
      occurred. Participants with a composite calcium score >=2 had a higher risk of CV
      events (11.1 events/100 person-years) than those with a score of 0 (5.5
      events/100 person-years, unadjusted hazard ratio [HR] 2.01, p <0.001), but this
      association was not significant after multivariate adjustment. The risk of death
      was higher in participants with a composite calcium score of >=2 (8.9 events/100
      person-years) versus those with a score of 0 (3.6 events/100 person-years,
      unadjusted HR 2.51, p <0.001). After adjustment for age, diabetes mellitus,
      previous coronary revascularization, diastolic blood pressure, estimated
      glomerular filtration rate, and serum phosphorus level, the risk of death
      remained higher in participants with a composite calcium score of >=2 compared
      with those with a score of 0 (adjusted HR 1.76, 95% confidence interval 1.10 to
      2.81, p = 0.02). In conclusion, a simple TTE-derived composite cardiac calcium
      score was independently predictive of death in patients with pre-existing CAD.

PMID- 25963225
TI  - Toward Quantifying the Prevalence, Severity, and Cost Associated With Patient
      Motion During Clinical MR Examinations.
AB  - PURPOSE: To assess the prevalence, severity, and cost estimates associated with
      motion artifacts identified on clinical MR examinations, with a focus on the
      neuroaxis. METHODS: A retrospective review of 1 randomly selected full calendar
      week of MR examinations (April 2014) was conducted for the detection of
      significant motion artifacts in examinations performed at a single institution on
      3 different MR scanners. A base-case cost estimate was computed from recently
      available institutional data, and correlated with sequence time and severity of
      motion artifacts. RESULTS: A total of 192 completed clinical examinations were
      reviewed. Significant motion artifacts were identified on sequences in 7.5% of
      outpatient and 29.4% of inpatient and/or emergency department MR examinations.
      The prevalence of repeat sequences was 19.8% of total MRI examinations. The base
      case cost estimate yielded a potential cost to the hospital of $592 per hour in
      lost revenue due to motion artifacts. Potential institutional average costs borne
      (revenue forgone) of approximately $115,000 per scanner per year may affect
      hospitals, owing to motion artifacts (univariate sensitivity analysis suggested a
      lower bound of $92,600, and an upper bound of $139,000). CONCLUSIONS: Motion
      artifacts represent a frequent cause of MR image degradation, particularly for
      inpatient and emergency department patients, resulting in substantial costs to
      the radiology department. Greater attention and resources should be directed
      toward providing practical solutions to this dilemma.

PMID- 25963224
TI  - The role of point-of-care tests in antibiotic stewardship for urinary tract
      infections in a resource-limited setting on the Thailand-Myanmar border.
AB  - OBJECTIVE: Published literature from resource-limited settings is infrequent,
      although urinary tract infections (UTI) are a common cause of outpatient
      presentation and antibiotic use. Point-of-care test (POCT) interpretation relates
      to antibiotic use and antibiotic resistance. We aimed to assess the diagnostic
      accuracy of POCT and their role in UTI antibiotic stewardship. METHODS: One-year
      retrospective analysis in three clinics on the Thailand-Myanmar border of non
      pregnant adults presenting with urinary symptoms. POCT (urine dipstick and
      microscopy) were compared to culture with significant growth classified as pure
      growth of a single organism >10(5)  CFU/ml. RESULTS: In 247 patients, 82.6%
      female, the most common symptoms were dysuria (81.2%), suprapubic pain (67.8%)
      and urinary frequency (53.7%). After excluding contaminated samples, UTI was
      diagnosed in 52.4% (97/185); 71.1% (69/97) had a significant growth on culture,
      and >80% of these were Escherichia coli (20.9% produced extended-spectrum beta
      lactamase (ESBL)). Positive urine dipstick (leucocyte esterase >=1 and/or nitrate
      positive) compared against positive microscopy (white blood cell >10/HPF,
      bacteria >=1/HPF, epithelial cells <5/HPF) had a higher sensitivity (99% vs. 57%)
      but a lower specificity (47% vs. 89%), respectively. Combined POCT resulted in
      the best sensitivity (98%) and specificity (81%). Nearly one in ten patients
      received an antimicrobial to which the organism was not fully sensitive.
      CONCLUSION: One rapid, cost-effective POCT was too inaccurate to be used alone by
      healthcare workers, impeding antibiotic stewardship in a high ESBL setting.
      Appropriate prescribing is improved with concurrent use and concordant results of
      urine dipstick and microscopy.

PMID- 25963226
TI  - Optofluidic guiding, valving, switching and mixing based on plasmonic heating in
      a random gold nanoisland substrate.
AB  - We present a versatile optofluidic flow manipulation scheme based on plasmonic
      heating in a random gold nanoisland substrate (Au-NIS). With its highly efficient
      conversion of optical power to hydrodynamic actuation, the reported substrate is
      used for laser-controlled optofluidic manipulation. It is the first time that
      microfluidic flow guiding, valving, and mixing within the same functional
      substrate has been realised. Plasmonic heating provides power for guiding the
      sample flow inside a microfluidic channel at controlled speed and transport of
      small particles or living cells is demonstrated. We have also made a laser
      actuated microfluidic valve through controlling the surface wettability of the
      sample/Au-NIS interface. When the laser power density is sufficiently high to
      generate a bubble, localized convection around the bubble can lead to efficient
      sample mixing within a microfluidic chamber. The reported Au-NIS scheme
      practically offers a programmable functional surface on which users have the
      freedom to control the wetting characteristics with a focused laser beam. We have
      verified that this optofluidic approach induces insignificant degradation in cell
      viability. The reported scheme therefore offers a wide range of application
      possibilities in microfluidics and biomedical engineering, particularly those
      operated under a low Reynolds number. 

PMID- 25963227
TI  - Anti-Trichomonas vaginalis properties of the oil of Amomum tsao-ko and its major
      component, geraniol.
AB  - CONTEXT: Trichomonosis, caused by the flagellate protozoan Trichomonas vaginalis,
      is the most common non-viral sexually transmitted disease (STD) and 5
      nitroimidazole drugs are used for the treatment. However, a growing number of T.
      vaginalis isolates are resistant to these drugs, which make it becomes an urgent
      issue. OBJECTIVE: The current study was designed to evaluate the anti-T.
      vaginalis activity of the essential oil from A. tsao-ko used in traditional
      Chinese medicine and as a spice and its main component, geraniol. MATERIALS AND
      METHODS: The anti-T. vaginalis activities of A. tsao-ko essential oil and
      geraniol were evaluated by the minimum lethal concentration (MLC) and 50%
      inhibitory concentration (IC50) in vitro. The morphological changes of T.
      vaginalis were observed by transmission electron microscopy (TEM). Additionally,
      sub-MLC concentration treatment with sub-MLC A. tsao-ko essential oil and
      geraniol was also performed. RESULTS: This study shows that MLC/IC50 of A. tsao
      ko essential oil was 44.97 ug/ml/22.49 ug/ml for T. vaginalis isolate Tv1, and
      89.93 ug/ml/44.97 ug/ml for T. vaginalis isolate Tv2. Those of geraniol were
      342.96 ug/ml/171.48 ug/ml, respectively. After A. tsao-ko essential oil or
      geraniol treatment, obvious similar morphological changes of T. vaginalis were
      observed by TEM: the nuclear membrane was damaged, nuclei were dissolved, and the
      chromatin was accumulated; in the cytoplasm, numerous vacuoles appeared, rough
      endoplasmic reticulum dilated, the number of ribosomes were reduced, organelles
      disintegrated, the cell membrane was partially damaged, with cytoplasmic leakage,
      and cell disintegration was observed. The action time did not increase the effect
      of A. tsao-ko essential oil or geraniol against T. vaginalis, as no significant
      difference was observed after sub-MLC concentration treatment for 1, 3, and 5 h
      with A. tsao-ko essential oil and geraniol. DISCUSSION AND CONCLUSION: The study
      describes the first report on the activity and morphological changes of A. tsao
      ko essential oil and geraniol against T. vaginalis. The results obtained herein
      presented new opportunities for antitrichomonal drugs.

PMID- 25963228
TI  - Cryptoporus volvatus polysaccharides attenuate LPS-induced expression of pro
      inflammatory factors via the TLR2 signaling pathway in human alveolar epithelial
      cells.
AB  - CONTEXT: Cryptoporus volvatus (Peck) Hubb grows wild in China, and its fruiting
      bodies have been used traditionally to treat asthma and bronchitis. OBJECTIVES:
      This study evaluates the anti-inflammatory effect of Cryptoporus polysaccharides
      (CP) extracted from fruiting bodies of C. volvatus on lipopolysaccharide (LPS)
      induced pro-inflammatory factors and the signaling pathways involved in human
      alveolar epithelial cells. MATERIALS AND METHODS: To evaluate the effects of CP
      on LPS-induced pro-inflammatory factors, A549 cells were pre-incubated with CP 1,
      10, and 100 MUg/ml for 1 h and then stimulated with LPS 10 MUg/ml for 24 h. The
      expression of pro-inflammatory factors monocyte chemoattractant protein-1 (MCP
      1), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), Toll
      like receptor 2 (TLR2), and phosphorylation of ERK1/2, p38, and NF-kappaB p65
      were measured by q-PCR, ELISA, and western blotting. RESULTS: CP decreased LPS
      induced mRNA expression of MCP-1, TNF-alpha, and IL-1beta (IC50 = 83.3, 85.2, and
      91.6 MUg/ml, respectively) and their correspondent protein expression (IC50 =
      88.6, 76.4, and 81.6 MUg/ml, respectively). Investigation of potential mechanisms
      indicated that CP 100 MUg/ml reduced LPS-induced expression of TLR2 mRNA (66.9%,
      p < 0.01) and protein (63.2%, p < 0.01) that was a result of the decreased pro
      inflammatory factors. LPS induction increased the expression of TLR2 and the
      phosphorylation of p38 and ERK1/2, NF-kB p65 concomitantly. CP 100 MUg/ml
      inhibited the LPS-induced phosphorylation of the signaling proteins (p < 0.05).
      CONCLUSIONS: This suggests that CP pretreatment down-regulates LPS-mediated
      inflammation in lung epithelial cells. This study further confirmed that CP is a
      potential anti-inflammatory drug for the treatment of airway inflammatory
      diseases.

PMID- 25963229
TI  - A validated HPLC-UV method and optimization of sample preparation technique for
      norepinephrine and serotonin in mouse brain.
AB  - CONTEXT: Norepinephrine and serotonin are two important neurotransmitters whose
      variations in brain are reported to be associated with many common
      neuropsychiatric disorders. Yet, relevant literature on estimation of monoamines
      in biological samples using HPLC-UV is limited. OBJECTIVE: The present study
      involves the development of a simultaneous HPLC-UV method for estimation of
      norepinephrine and serotonin along with optimization of the sample preparation
      technique. MATERIALS AND METHODS: Chromatographic separation was achieved by
      injecting 20 uL of the sample after extraction into Quaternary pump HPLC equipped
      with C18 column using 0.05% formic acid and acetonitrile (90:10, v/v) as the
      mobile phase with 1 mL min(-1) flow rate. The developed method was validated as
      per the ICH guidelines in terms of linearity, accuracy, repeatability, precision,
      and robustness. RESULTS AND DISCUSSION: The method showed a wide range of
      linearity (50-4000 and 31.25-4000 ng mL(-1) for norepinephrine and serotonin,
      respectively). The recovery was found to be in the range of 86.04-89.01% and
      86.43-89.61% for norepinephrine and serotonin, respectively. The results showed
      low value of %RSD for repeatability, intra and inter-day precision, and
      robustness studies. Four different methods were used for the extraction of these
      neurotransmitters and the best one with maximum recovery was ascertained.
      CONCLUSION: Here, we developed and validated a simple, accurate, and reliable
      method for the estimation of norepinephrine and serotonin in mice brain samples
      using HPLC-UV. The method was successfully applied to quantify these
      neurotransmitters in mice brain extracted by optimized sample preparation
      technique.

PMID- 25963230
TI  - A Systematic Review of Physicians' and Pharmacists' Perspectives on Generic Drug
      Use: What are the Global Challenges?
AB  - BACKGROUND AND OBJECTIVES: Generic substitution has been introduced in most
      countries in order to reduce costs and improve access to drugs. However,
      regulations and the generic drugs available vary between countries. It is the
      prescriber or dispenser of the drug who is the final decision maker.
      Nevertheless, physicians' and pharmacists' perceptions of generic drug use are
      not well documented to date. This study presents a systematic review of
      physicians' and pharmacists' perspectives on generic drug use worldwide. METHODS:
      A systematic literature search was performed to retrieve all articles published
      between 2002 and 2012 regarding physicians' and/or pharmacists' experiences with
      generic drugs and generic substitution. RESULTS: Of 1322 publications initially
      identified, 24 were eligible for inclusion. Overall, the studies revealed that
      physicians and pharmacists were aware of the cost-saving function of generic
      drugs and their role in improving global access to drugs. Nevertheless, marked
      differences were observed between countries when studying physicians' and
      pharmacists' perceptions of the available generic drugs. In less mature
      healthcare systems, large variations regarding, for example, control routines,
      bioequivalence requirements, and manufacturer standards were reported. A lack of
      reliable information and mistrust in the efficacy and quality were also mentioned
      by these participants. In the most developed healthcare systems, the participants
      trusted the quality of the generic drugs and did not hesitate to offer them to
      all patients regardless of socioeconomic status. In general, pharmacists seemed
      to have better knowledge of the concept of bioequivalence and generic drug
      aspects than physicians. CONCLUSIONS: The present study indicates that physicians
      and pharmacists are aware of the role of generic drugs in the improvement of
      global access to drugs. However, there are marked differences regarding how these
      health professionals view the quality of generic drugs depending on the maturity
      of their country's healthcare system. This can be attributed to the fact that
      developed healthcare systems have more reliable public control routines for drugs
      in general as well as better bioequivalence requirements concerning generics in
      particular.

PMID- 25963231
TI  - Memories of Stephen Hough (27.08.1947-05.12.2014).

PMID- 25963232
TI  - Anti-osteoporosis drug prescribing after hip fracture in the UK: 2000-2010.
AB  - The probability of initiating with anti-osteoporosis therapy increased from 7 %
      in 2000 to 46 % in 2010. This improvement was greater for patients over the age
      of 75 years. Men, those overweight, having dementia or exposed to antipsychotics,
      sedatives/hypnotics or opioid analgesics were significantly less likely to
      receive anti-osteoporosis drugs. INTRODUCTION: The objective of this study was to
      examine trends and determinants of anti-osteoporosis drug prescribing after hip
      fracture in the UK between 2000 and 2010. METHODS: Data were extracted from the
      UK Clinical Practice Research Datalink for patients >=50 years who had a first
      hip fracture between 2000 and 2010 and who did not currently (<=6 months prior)
      receive anti-osteoporosis drugs (bisphosphonates, strontium ranelate, parathyroid
      hormone, calcitonin and raloxifene) (n = 27,542). The cumulative incidence
      probability of being prescribed anti-osteoporosis drugs within 1 year after hip
      fracture was estimated by Kaplan-Meier life-table analyses. Determinants for
      treatment initiation were estimated by Cox proportional hazards models. RESULTS:
      The probability of being prescribed any anti-osteoporosis drug after hip fracture
      increased from 7 % in 2000 to 46 % in 2010. This trend was more marked in
      patients >=75 years. The increase in prescribing of anti-osteoporosis drugs was
      complemented by a similar increase in vitamin D/calcium provision. Cumulative
      incidence of receiving anti-osteoporosis therapy was greater at any given point
      in time in women (8 % in 2000, 51 % in 2010) compared to men (4 % in 2000, 34 %
      in 2010). In addition to male gender, multivariable Cox regression identified
      reduced likelihood of receiving anti-osteoporosis drugs for those being
      overweight, having dementia and exposed to psychotropic drugs (antipsychotics,
      sedatives/hypnotics) or opioid analgesics. CONCLUSION: Although the prescribing
      of anti-osteoporosis drugs after hip fracture has increased substantially since
      2000, the overall rate remained inadequate, particularly in men. With the
      continuing increase in the absolute number of hip fractures, further research
      should be made into the barriers to optimise osteoporosis management.

PMID- 25963233
TI  - Exercise capacity independently predicts bone mineral density and proximal
      femoral geometry in patients with acute decompensated heart failure.
AB  - Heart failure is associated with increased risk of osteoporosis. We evaluated the
      prevalence and predictors of osteoporosis in hospitalized patients with ADHF
      using quantitative computed tomography. Osteoporosis and vertebral fracture are
      prevalent in patients with ADHF and exercise capacity independently predicts bone
      mass and femoral bone geometry. INTRODUCTION: Heart failure is associated with
      reduced bone mass and increased risk of osteoporotic fractures. However, the
      prevalence and predictors of osteoporosis in hospitalized patients with acute
      decompensated heart failure (ADHF) are not well understood. METHODS: Sixty-five
      patients (15 postmenopausal females and 50 males) with ADHF were prospectively
      and consecutively enrolled. After stabilization of heart failure symptoms,
      quantitative computed tomography for bone mineral density (BMD) and femoral
      geometry as well as biochemical, echocardiographic, and cardiopulmonary exercise
      tests were performed. RESULTS: Fifteen postmenopausal female showed a high
      prevalence of osteoporosis (40%) and vertebral fracture (53%). Among 50 male
      patients, 12% had osteoporosis and 32% had osteopenia, while vertebral fracture
      was found in 12%. Lumbar volumetric BMD (vBMD) was significantly lower in
      ischemic patients than non-ischemic patients (107.9 +/- 47.5 vs. 145.4 +/- 40.9
      mg/cm(3), p = 0.005) in male. Exercise capacity, indicated by peak oxygen
      consumption (VO2), was significantly associated with lumbar vBMD (r = 0.576, p <
      0.001) and total hip areal BMD (aBMD) (r = 0.512, p = 0.001) and cortical
      thickness of the femur neck (r = 0.544, p = 0.001). When controlled for age, body
      mass index, N-terminal proBrain natriuretic protein (NT-proBNP), etiology of
      heart failure, hemoglobin, and thigh circumference, multivariate regression
      analysis revealed peak VO2 independently predicted lumbar vBMD (beta = 0.448, p =
      0.031), total hip aBMD (beta = 0.547, p = 0.021), and cortical thickness of the
      femur neck (beta = 0.590, p = 0.011). CONCLUSION: In male patients with ADHF,
      osteoporosis and vertebral fracture are prevalent, and exercise capacity
      independently predicts bone mass and geometry. Given that heart failure patients
      with reduced exercise capacity carry a substantial increased risk of fracture,
      proper osteoporosis evaluation is important in these patients.

PMID- 25963234
TI  - Role of vitamin D levels and vitamin D supplementation on bone mineral density in
      Klinefelter syndrome.
AB  - This manuscript describes the role of low vitamin D in bone metabolism of
      Klinefelter subjects. Low vitamin D is frequent in this condition and seems to be
      more important than testosterone in inducing low bone mineral density (BMD) and
      osteoporosis. Supplementation with vitamin D restores BMD after 2 years of
      treatment, whereas testosterone alone seems to be ineffective. INTRODUCTION:
      Decreased bone mineral density (BMD) in Klinefelter syndrome (KS) is frequent,
      and it has been traditionally related to low testosterone (T) levels. However,
      low BMD can be observed also in patients with normal T levels and T replacement
      therapy does not necessarily increase bone mass in these patients. Nothing is
      known about vitamin D levels and supplementation in KS. In this study, we
      determine vitamin D status and bone mass in KS subjects and compare the efficacy
      of T therapy and vitamin D supplementation on BMD. METHODS: A total of 127 non
      mosaic KS patients and 60 age-matched male controls were evaluated with
      reproductive hormones, 25-hydroxyvitamin D, PTH, and bone densitometry by dual
      energy X-ray absorptiometry (DEXA). Patients with hypogonadism and/or 25
      hydroxyvitamin D deficiency were treated with T-gel 2% and/or calcifediol and re
      evaluated after 24 months of treatment. RESULTS: 25-hydroxyvitamin D levels were
      significantly lower in KS patients with respect to controls, and they had
      significantly lower lumbar and femoral BMD. The percentage of
      osteopenia/osteoporosis in subjects with 25-hydroxyvitamin D deficiency was
      higher with respect to subjects with normal 25-hydroxyvitamin D and was not
      related to the presence/absence of low T levels. Subjects treated with
      calcifediol or T + calcifediol had a significant increase in lumbar BMD after
      treatment. No difference was found in T-treated group. CONCLUSIONS: These data
      highlight that low 25-hydroxyvitamin D levels seem to have a more critical role
      than low T levels in inducing low BMD in KS subjects. Furthermore, vitamin D
      supplementation seems to be more effective than T replacement therapy alone in
      increasing BMD.

PMID- 25963235
TI  - Attenuation of hind-limb suspension-induced bone loss by curcumin is associated
      with reduced oxidative stress and increased vitamin D receptor expression.
AB  - Treatment with curcumin attenuated modeled microgravity-induced bone loss,
      possibly through abating oxidative stress and activating vitamin D receptor.
      Curcumin might be an effective countermeasure for microgravity-induced bone loss
      but remains to be tested in humans. INTRODUCTION: Bone loss is one of the most
      important complications for human crewmembers who are exposed to long-term
      microgravity in space and also for bedridden people. The aim of the current study
      was to elucidate whether treatment with curcumin attenuated bone loss induced by
      microgravity. METHODS: We used hind-limb suspension (HLS) and rotary wall vessel
      bioreactor (RWVB) to model microgravity in vivo and in vitro, respectively. We
      investigated the effects of curcumin consumption (40 mg kg(-1) body weight day(
      1), via daily oral gavages) on Sprague-Dawley (SD) rats exposed to HLS for 6
      weeks. Then, we investigated the effects of incubation with curcumin (4 MUM) on
      MC3T3-E1 and RAW264.7 cells cultured in RWVB. RESULTS: Curcumin alleviated HLS
      induced reduction of bone mineral density in tibiae and preserved bone structure
      in tibiae and mechanical strength in femurs. Curcumin alleviated HLS-induced
      oxidative stress marked by reduced malondialdehyde content and increased total
      sulfhydryl content in femurs. In cultured MC3T3-E1 cells, curcumin inhibited
      modeled microgravity-induced reactive oxygen species (ROS) formation and enhanced
      osteoblastic differentiation. In cultured RAW264.7 cells, curcumin reduced
      modeled microgravity-induced ROS formation and attenuated osteoclastogenesis. In
      addition, curcumin upregulated vitamin D receptor (VDR) expression in femurs of
      rats exposed to HLS and MC3T3-E1 cells exposed to modeled microgravity.
      CONCLUSION: Curcumin alleviated HLS-induced bone loss in rats, possibly via
      suppressing oxidative stress and upregulating VDR expression.

PMID- 25963236
TI  - Improvement of spinal alignment and quality of life after corrective surgery for
      spinal kyphosis in patients with osteoporosis: a comparative study with non
      operated patients.
AB  - This study evaluated changes in spinal alignment and quality of life (QOL) after
      corrective spinal surgery for patients with postmenopausal osteoporosis and
      spinal kyphosis. Spinal global alignment and QOL were significantly improved
      after corrective spinal surgery but did not reach the level of non-operated
      controls. INTRODUCTION: With the increased aging of society, the demand for
      corrective spinal instrumentation for spinal kyphosis in osteoporotic patients is
      increasing. However, previous studies have not focused on the improvement of
      quality of life (QOL) after corrective spinal surgery in patients with
      osteoporosis, compared to non-operated control patients. The purposes of this
      study were thus to evaluate changes in spinal alignment and QOL after corrective
      spinal instrumentation for patients with osteoporosis and spinal kyphosis and to
      compare these results with non-operated patients. METHODS: Participants comprised
      39 patients with postmenopausal osteoporosis >=50 years old who underwent
      corrective spinal surgery using multilevel posterior lumbar interbody fusion
      (PLIF) for symptomatic thoracolumbar or lumbar kyphosis, and 82 age-matched
      patients with postmenopausal osteoporosis without prevalent vertebral fractures.
      Spinopelvic parameters were evaluated with standing lateral spine radiography,
      and QOL was evaluated with the Japanese Osteoporosis QOL Questionnaire (JOQOL),
      SF-36, and Roland-Morris Disability Questionnaire (RDQ). RESULTS: Lumbar kyphosis
      angle, sagittal vertical axis, and pelvic tilt were significantly improved
      postoperatively. QOL evaluated with all three questionnaires also significantly
      improved after 6 months postoperatively, particularly in domain and subscale
      scores for pain and general/mental health. However, these radiographic
      parameters, total JOQOL score, SF-36 physical component summary score, and RDQ
      score were significantly inferior compared with non-operated controls.
      CONCLUSIONS: The results indicate that spinal global alignment and QOL were
      significantly improved after corrective spinal surgery using multilevel PLIF for
      patients with osteoporosis and spinal kyphosis but did not reach the level of non
      operated controls.

PMID- 25963237
TI  - Exercise and fractures in postmenopausal women. Final results of the controlled
      Erlangen Fitness and Osteoporosis Prevention Study (EFOPS).
AB  - The EFOPS trial clearly established the positive effect of long-term exercise on
      clinical low-trauma fractures in postmenopausal women at risk. Bearing in mind
      that the complex anti-fracture exercise protocols also affect a large variety of
      diseases of increased age, we strongly encourage older adults to perform
      multipurpose exercise programs. INTRODUCTION: Physical exercise may be an
      efficient option for autonomous fracture prevention during increasing age. The
      aim of the study was to evaluate the effect of exercise on clinical overall
      fracture incidence and bone mineral density (BMD) in elderly subjects at risk.
      METHODS: In 1998 initially, 137 early-postmenopausal, osteopenic women living in
      Erlangen-Nuremberg, Germany, were included in the EFOPS trial. Subjects of the
      exercise group (EG; n = 86) conducted two supervised group and two home exercise
      sessions/week while the control group (CG; n = 51) was requested to maintain
      their physical activity. Primary study endpoints were clinical overall low-trauma
      fractures determined by questionnaires, structured interviews, and BMD at the
      lumbar spine and femoral neck assessed by dual-energy X-ray absorptiometry.
      RESULTS: In 2014, 105 subjects (EG: n = 59 vs. CG: n = 46) representing 1680
      participant-years were included in the 16-year follow-up analysis. Risk ratio in
      the EG for overall low-trauma fractures was 0.51 (95% confidence interval (95%
      CI) 0.23 to 0.97, p = .046), rate ratio was 0.42 (95% CI 0.20 to 0.86, p = .018).
      Based on comparable baseline values, lumbar spine (MV -1.5%, 95% CI -0.1 to -2.8
      vs. -5.8%, -3.3 to -7.2%) and femoral neck (-6.5%, -5.2 to -7.7 vs. -9.6%, -8.2
      to 11.1%) BMD decreased in both groups; however, the reduction was more
      pronounced in the CG (p <= .001). CONCLUSION: This study clearly evidenced the
      high anti-fracture efficiency of multipurpose exercise programs. Considering
      furthermore the favorable effect of exercise on most other risk factors of
      increasing age, we strongly encourage older adults to perform multipurpose
      exercise programs.

PMID- 25963238
TI  - Depression Among People Who Inject Drugs and Their Intimate Partners in
      Kazakhstan.
AB  - This paper examines individual, social, and structural factors associated with
      depression among 728 people who inject drugs (PWID) and their intimate partners
      in Kazakhstan, with separate multivariate models by gender. Depression scores
      were higher on average among participants of both genders who recently
      experienced sexual intimate partner violence, food insecurity, and who had lower
      levels of self-rated health. Among females, higher depression scores were
      associated with experiencing childhood sexual abuse, lower levels of social
      support, and not having children. Findings highlight a need to incorporate gender
      differences and factors associated with depression in designing mental health
      services for PWID in Kazakhstan.

PMID- 25963239
TI  - Nematode dermatitis due to Angiostrongylus vasorum infection in a dog.
AB  - BACKGROUND: Angiostrongylus vasorum is a nematode that primarily infects Canidae.
      The adult parasites are found in the pulmonary arterial circulation and the right
      side of the heart. The most common clinical sign is respiratory dysfunction.
      Bleeding, neurological, ocular, cardiovascular and gastrointestinal disorders are
      also reported. Skin lesions are very unusual. HYPOTHESIS/OBJECTIVES: This report
      describes a nematode dermatitis due to A. vasorum infection. To the best of the
      authors' knowledge, this is the first case of a dog infected with this parasite
      that initially presented with skin lesions only. ANIMAL: A 3-year-old female
      Weimaraner dog presented with a crusted papular dermatitis on the bridge of the
      nose and on the pinnae, and an erythematous pododermatitis with erosions and
      perionyxis of one digit of 1 week's duration. Two weeks later the dog developed
      respiratory distress. METHODS AND RESULTS: Skin scrapings and fungal culture were
      negative for parasites and dermatophytes. Histopathological examination showed
      dermal granulomas and pyogranulomas with eosinophils centred around parasitic
      elements compatible with nematode larvae. Angiostrongylus vasorum DNA was
      demonstrated in skin biopsies. Chest radiographs were compatible with verminous
      pneumonia and a Baermann test revealed A. vasorum larvae. The dog was treated
      orally with fenbendazole, with rapid improvement and complete cure after 3
      months. CONCLUSIONS AND CLINICAL IMPORTANCE: Angiostrongylus vasorum should be
      considered in dogs presented with skin lesions and respiratory signs. Skin
      biopsy, chest radiographs and Baermann test should be included in the diagnostic
      investigation.

PMID- 25963240
TI  - Agreement and mortality prediction in high-resolution CT of diffuse fibrotic lung
      disease.
AB  - INTRODUCTION: The prognosis of diffuse fibrotic lung disease (DFLD) is known to
      be variable, but there is a paucity of literature on prognostic markers
      independent of precise clinical diagnosis. This study aimed to assess the
      mortality prediction of three high-resolution computed tomography (HRCT) scores
      in a heterogeneous population of patients with DFLD. A large radiologist and
      physician reader group was used to determine agreement among readers of varying
      background in applying these scores. METHODS: Institutional review board approval
      was obtained. Informed consent was waived for this retrospective study. Eighty
      HRCTs in 68 patients with DFLD (35 men, mean age 72.9 years) were evaluated
      retrospectively by 18 readers. Readers included thoracic and general
      radiologists, respiratory physicians and radiology trainees. Features scored were
      honeycombing, extent of disease and traction bronchiectasis. Demographics,
      diagnosis and pulmonary function data were collected. Patients were categorised
      as having either idiopathic pulmonary fibrosis, fibrosis relating to connective
      tissue disease, 'miscellaneous' DFLD or 'undefined', where no single entity was
      felt entirely or confidently to explain the pulmonary disease. Agreement was
      assessed using the kappa statistic. Associations with mortality were analysed
      using the Cox marginal model. RESULTS: Agreement was better for honeycombing
      (kappa = 0.44) and disease extent (kappa = 0.47) than traction bronchiectasis
      (kappa = 0.24). Honeycombing presence (P < 0.0005) and disease extent >30% (P =
      0.002) predicted increased mortality independent of clinical diagnosis. Traction
      bronchiectasis was non-predictive. Clinical diagnosis was not an independent
      predictor, but age was independently associated with mortality (P = 0.004).
      Pulmonary function data were only available for 43 patients, but in a limited
      subanalysis, the diffusion capacity of carbon monoxide was independently
      predictive of increased mortality (P = 0.005). CONCLUSIONS: The presence of
      honeycombing and a greater extent of fibrotic lung disease predict increased
      mortality independent of clinical diagnosis. Our large, mixed-expertise reader
      group shows moderate interobserver agreement, comparable with agreement values
      for these scores in the literature.

PMID- 25963241
TI  - Optogenetic control of molecular motors and organelle distributions in cells.
AB  - Intracellular transport and distribution of organelles play important roles in
      diverse cellular functions, including cell polarization, intracellular signaling,
      cell survival, and apoptosis. Here, we report an optogenetic strategy to control
      the transport and distribution of organelles by light. This is achieved by
      optically recruiting molecular motors onto organelles through the
      heterodimerization of Arabidopsis thaliana cryptochrome 2 (CRY2) and its
      interacting partner CIB1. CRY2 and CIB1 dimerize within subseconds upon exposure
      to blue light, which requires no exogenous ligands and low intensity of light. We
      demonstrate that mitochondria, peroxisomes, and lysosomes can be driven toward
      the cell periphery upon light-induced recruitment of kinesin, or toward the cell
      nucleus upon recruitment of dynein. Light-induced motor recruitment and organelle
      movements are repeatable, reversible, and can be achieved at subcellular regions.
      This light-controlled organelle redistribution provides a new strategy for
      studying the causal roles of organelle transport and distribution in cellular
      functions in living cells.

PMID- 25963242
TI  - Proteomic-based biotyping reveals hidden diversity within a microalgae culture
      collection: An example using Dunaliella.
AB  - Accurate and defendable taxonomic identification of microalgae strains is vital
      for culture collections, industry and academia; particularly when addressing
      issues of intellectual property. We demonstrate the remarkable effectiveness of
      Matrix Assisted Laser Desorption Ionisation Time of Flight Mass Spectrometry
      (MALDI-TOF-MS) biotyping to deliver rapid and accurate strain separation, even in
      situations where standard molecular tools prove ineffective. Highly distinctive
      MALDI spectra were obtained for thirty two biotechnologically interesting
      Dunaliella strains plus strains of Arthrospira, Chlorella, Isochrysis,
      Tetraselmis and a range of culturable co-occurring bacteria. Spectra were
      directly compared with genomic DNA sequences (internal transcribed spacer, ITS).
      Within individual Dunaliella isolates MALDI discriminated between strains with
      identical ITS sequences, thereby emphasising and enhancing knowledge of the
      diversity within microalgae culture collections. Further, MALDI spectra did not
      vary with culture age or growth stage during the course of the experiment;
      therefore MALDI presents stable and accurate strain-specific signature spectra.
      Bacterial contamination did not affect MALDI's discriminating power. Biotyping by
      MALDI-TOF-MS will prove effective in situations wherein precise strain
      identification is vital, for example in cases involving intellectual property
      disputes and in monitoring and safeguarding biosecurity. MALDI should be accepted
      as a biotyping tool to complement and enhance standard molecular taxonomy for
      microalgae. 

PMID- 25963243
TI  - Imaging features of primary and recurrent intrathoracic synovial sarcoma: a
      single-institute experience.
AB  - OBJECTIVE: The objective was to study the imaging features of primary and
      metastatic intrathoracic synovial sarcoma (ISS). MATERIALS AND METHODS: We
      reviewed the imaging of 42 patients with ISS (31 pleural, 7 intrapulmonary, 4
      mediastinal), with baseline imaging of 19 patients and follow-up imaging in all.
      RESULTS: Primary tumors (n=19) were well circumscribed (15/19), homogeneous or
      heterogeneously enhancing, with mean size 9.1 cm (range: 1.8-25 cm).
      Recurrent/metastatic disease developed in 28/42 patients (67%). Lung was the most
      common site of metastases (21/28), with most of them predominantly pleural
      (11/21). On pathology, 30 patients had monophasic tumors, and 6 each had biphasic
      tumors and poorly differentiated tumors. CONCLUSION: Intrathoracic SS most
      commonly presents as a large heterogeneous pleural mass without associated
      adenopathy. Lung metastases are often pleural based and ipsilateral.

PMID- 25963244
TI  - Unusual extraosseous extension of jaw lesion into the temporal fossa.
AB  - The keratocystic odontogenic tumor (KCOT) is a relatively rare, benign neoplasm
      that develops in the maxilla or mandible, arising from the dental lamina or basal
      cells of the oral epithelium. The disease is characterized by aggressive growth
      and a high recurrence rate following surgical treatment. We present a case of a
      55-year-old man with a giant KCOT of the mandible. The imaging features and
      differential diagnosis are described with discussion of the surgical management. 

PMID- 25963245
TI  - A Nonlocal Model for Contact Attraction and Repulsion in Heterogeneous Cell
      Populations.
AB  - Instructing others to move is fundamental for many populations, whether animal or
      cellular. In many instances, these commands are transmitted by contact, such that
      an instruction is relayed directly (e.g. by touch) from signaller to receiver:
      for cells, this can occur via receptor-ligand mediated interactions at their
      membranes, potentially at a distance if a cell extends long filopodia. Given that
      commands ranging from attractive to repelling can be transmitted over variable
      distances and between cells of the same (homotypic) or different (heterotypic)
      type, these mechanisms can clearly have a significant impact on the organisation
      of a tissue. In this paper, we extend a system of nonlocal partial differential
      equations (integrodifferential equations) to provide a general modelling
      framework to explore these processes, performing linear stability and numerical
      analyses to reveal its capacity to trigger the self-organisation of tissues. We
      demonstrate the potential of the framework via two illustrative applications: the
      contact-mediated dispersal of neural crest populations and the self-organisation
      of pigmentation patterns in zebrafish. 

PMID- 25963246
TI  - Wavelength Selection in Gyrotactic Bioconvection.
AB  - We investigate pattern formation by swimming micro-organisms (bioconvection),
      when their orientation is determined by balance between gravitational and viscous
      torques (gyrotaxis), due to being bottom heavy. The governing equations, which
      consist of the Navier-Stokes equations for an incompressible fluid coupled with a
      micro-organism conservation equation, are solved numerically in a large cross
      section chamber with periodic boundary conditions in the horizontal directions.
      The influence of key parameters on wavelength selection in bioconvection patterns
      is investigated numerically. For realistic ranges of parameter values, the
      computed wavelengths are in good agreement with the experimental observations
      provided that the diffusion due to randomness in cell swimming behaviour is
      small, refuting a recently published claim that the mathematical model becomes
      inaccurate at long times. We also provide the first computational evidence of
      "bottom-standing" plumes in a three-dimensional simulation. 

PMID- 25963247
TI  - Identifying patients who may benefit from inferior turbinate reduction using
      computer simulations.
AB  - OBJECTIVES/HYPOTHESIS: (1) To determine objective criteria to predict which
      patients may benefit most from inferior turbinate reduction surgery. (2) To test
      whether the site of turbinate reduction, either along the nasal floor (bottom
      resection) or along the septal side (medial resection), impacts the extent to
      which nasal resistance is reduced. STUDY DESIGN: Case series. METHODS: Three
      dimensional reconstructions of the nasal anatomy of five nasal airway obstruction
      patients were created based on presurgical computed tomography scans. Inferior
      turbinate reduction models were created for each patient using virtual surgery.
      Airflow, heat transfer, and humidity transport during inspiration were simulated
      using computational fluid dynamics (CFD). RESULTS: Nasal resistance curves
      revealed little to no difference between bottom resection and medial resection
      models. In two patients, little change was observed in nasal resistance after
      virtual inferior turbinate reduction, which was attributed to the narrowest cross
      sections being restricted to the anterior nose (i.e., anterior to the inferior
      turbinate). The three patients whose nasal resistances decreased substantially
      after virtual inferior turbinate reduction had a narrower airspace in the
      turbinate region and higher nasal resistance presurgery. Nasal air conditioning
      capacity was more affected by medial resections. CONCLUSIONS: CFD simulations
      predicted no significant difference in the decrease in nasal resistance between
      virtual inferior turbinate reductions performed by bottom versus medial resection
      of the turbinate. However, bottom resections better preserved the calculated
      humidification efficiency. The simulations predicted that the greatest reduction
      in nasal resistance occurs in patients with the highest presurgical resistance in
      the turbinate region. LEVEL OF EVIDENCE: 4.

PMID- 25963248
TI  - Unraveling the mystery of cognitive reserve.

PMID- 25963250
TI  - Social and cultural issues in genetic counselling.

PMID- 25963249
TI  - Treating cutaneous aging with patented technologies.

PMID- 25963251
TI  - What history tells us XXXVII. CRISPR-Cas: The discovery of an immune system in
      prokaryotes.

PMID- 25963252
TI  - Sensory cues employed for the acquisition of familiarity-dependent recognition of
      a shoal of conspecifics by climbing perch (Anabas testudineus Bloch).
AB  - In this study we showed that a freshwater fish, the climbing perch (Anabas
      testudineus) is incapable of using chemical communication but employs visual cues
      to acquire familiarity and distinguish a familiar group of conspecifics from an
      unfamiliar one. Moreover, the isolation of olfactory signals from visual cues did
      not affect the recognition and preference for a familiar shoal in this species. 

PMID- 25963253
TI  - siRNAs targeting PB2 and NP genes potentially inhibit replication of Highly
      Pathogenic H5N1 Avian Influenza Virus.
AB  - Highly Pathogenic Avian Influenza (HPAI) H5N1 virus is a threat to animal and
      public health worldwide. Till date, the H5N1 virus has claimed 402 human lives,
      with a mortality rate of 58 percent and has caused the death or culling of
      millions of poultry since 2003. In this study, we have designed three siRNAs (PB2
      2235, PB2-479 and NP-865) targeting PB2 and NP genes of avian influenza virus and
      evaluated their potential, measured by hemagglutination (HA), plaque reduction
      and Real time RT-PCR assay, in inhibiting H5N1 virus
      (A/chicken/Navapur/7972/2006) replication in MDCK cells. The siRNAs caused 8- to
      16-fold reduction in virus HA titers at 24 h after challenged with 100TCID50 of
      virus. Among these siRNAs, PB2-2235 offered the highest inhibition of virus
      replication with 16-fold reduction in virus HA titer, 80 percent reduction in
      viral plaque counts and 94 percent inhibition in expression of specific RNA at 24
      h. The other two siRNAs had 68-73 percent and 87-88 percent reduction in viral
      plaque counts and RNA copy number, respectively. The effect of siRNA on H5N1
      virus replication continued till 48h (maximum observation period). These findings
      suggest that PB2-2235 could efficiently inhibit HPAI H5N1 virus replication. 

PMID- 25963254
TI  - Classification and expression analyses of homeobox genes from Dictyostelium
      discoideum.
AB  - Homeobox genes are compared between genomes in an attempt to understand the
      evolution of animal development. The ability of the protist, Dictyostelium
      discoideum, to shift between uni- and multicellularity makes this group ideal for
      studying the genetic changes that may have occurred during this transition. We
      present here the first genome-wide classification and comparative genomic
      analysis of the 14 homeobox genes present in D. discoideum. Based on the
      structural alignment of the homeodomains, they can be broadly divided into TALE
      and non-TALE classes. When individual homeobox genes were compared with members
      of known class or family, we could further classify them into 3 groups, namely,
      TALE, OTHER and NOVEL classes, but no HOX family was found. The 5 members of TALE
      class could be further divided into PBX, PKNOX, IRX and CUP families; 4 homeobox
      genes classified as NOVEL did not show any similarity to any known homeobox
      genes; while the remaining 5 were classified as OTHERS as they did show certain
      degree of similarity to few known homeobox genes. No unique RNA expression
      pattern during development of D. discoideum emerged for members of an individual
      group. Putative promoter analysis revealed binding sites for few homeobox
      transcription factors among many probable factors. 

PMID- 25963255
TI  - Riboflavin transporter-2 (rft-2) of Caenorhabditis elegans: Adaptive and
      developmental regulation.
AB  - Riboflavin transporters (rft-1 and rft-2), orthologous to human riboflavin
      transporter-3 (hRVFT-3), are identified and characterized in Caenorhabditis
      elegans. However, studies pertaining to functional contribution of rft-2 in
      maintaining body homeostatic riboflavin levels and its regulation are very
      limited. In this study, the expression pattern of rft-2 at different life stages
      of C. elegans was studied through real-time PCR, and found to be consistent from
      larval to adult stages that demonstrate its involvement in maintaining the body
      homeostatic riboflavin levels at whole animal level all through its life. A
      possible regulation of rft-2 expression at mRNA levels at whole animal was
      studied after adaptation to low and high concentrations of riboflavin. Abundance
      of rft-2 transcript was upregulated in riboflavin-deficient conditions (10 nM),
      while it was downregulated with riboflavin-supplemented conditions (2 mM) as
      compared with control (10 meu M). Further, the 5'-regulatory region of the rft-2
      gene was cloned, and transgenic nematodes expressing transcriptional rft-2
      promoter::GFP fusion constructs were generated. The expression of rft-2 was found
      to be adaptively regulated in vivo when transgenic worms were maintained under
      different extracellular riboflavin levels, which was also mediated partly via
      changes in the rft-2 levels that directs towards the possible involvement of
      transcriptional regulatory events. 

PMID- 25963256
TI  - Anti-tumour immune effect of oral administration of Lactobacillus plantarum to
      CT26 tumour-bearing mice.
AB  - Colorectal cancer (CRC) is one of the most prevalent forms of cancer that shows a
      high mortality and increasing incidence. There are numerous successful treatment
      options for CRC, including surgery, chemotherapy, radiotherapy and immunotherapy;
      however, their side effects and limitations are considerable. Probiotics may be
      an effective strategy for preventing and inhibiting tumour growth through
      stimulation of host innate and adaptive immunity. We investigated and compared
      potential anti-tumour immune responses induced by two isolated Lactobacillus
      strains, Lactobacillus plantarum A and Lactobacillus rhamnosus b, by pre
      inoculating mice with lactobacilli for 14 days. Subsequently, subcutaneous and
      orthotopic intestinal tumours were generated in the pre-inoculated mice using
      CT26 murine adenocarcinoma cells and were assessed for response against the
      tumour. Our results indicated that oral administration with L. plantarum
      inhibited CT26 cell growth in BALB/c mice and prolonged the survival time of
      tumour-bearing mice compared with mice administered L. rhamnosus. L. plantarum
      produced protective immunity against the challenge with CT26 cells by increasing
      the effector functions of CD8+ and natural killer (NK) cell infiltration into
      tumour tissue, up-regulation of IFN-gamma (but not IL-4 or IL-17) production, and
      promotion of Th1-type CD4+ T differentiation. Consequently, our results suggest
      that L. plantarum can enhance the anti-tumour immune response and delay tumour
      formation. 

PMID- 25963257
TI  - Suppression of induced but not developmental apoptosis in Drosophila by Ayurvedic
      Amalaki Rasayana and Rasa-Sindoor.
AB  - Earlier we showed formulation-specific beneficial effects of dietary supplement
      of Ayurvedic Amalaki Rasayana (AR, a herbal formulation) and Rasa-Sindoor (RS, a
      mercury-based organo-metallic formulation) on various biological parameters in
      Drosophila, parallel to traditional Ayurvedic literature. These formulations also
      suppressed cell death and pathology in fly models of neurodegeneration. To
      understand basis of inhibition of apoptosis, we examined effects of AR and RS on
      induced and developmental apoptosis in Drosophila. Dietary AR or RS significantly
      reduced apoptosis induced by GMR-GAL4-, sev-GAL4- or hs-GAL4-directed expression
      of Rpr, Hid or Grim (RHG) proapoptotic proteins or by GMR-GAL4-directed DIAP1
      RNAi, resulting in significant restoration of organism's viability and eye
      morphology. AR or RS supplement enhanced levels of inhibitor of apoptosis
      proteins, DIAP1 and DIAP2, and of Bancal/Hrb57A, while the levels of RHG proteins
      and of initiator Dronc and effecter Drice caspases were reduced in non-apoptotic
      wild type as well as in RHG over-expressing tissues. Levels of Dronc or Drice
      remained unaffected in cells developmentally destined to die so that
      developmental apoptosis occurred normally. Elevated levels of DIAPs and reduced
      levels of RHG proteins and caspases reflect a more robust physiological state of
      AR or RS fed organisms allowing them to tolerate greater insults without
      triggering the cell-death response. Such homeostatic effects of these Rasayanas
      seem to contribute to 'healthy ageing', one of their effects suggested in
      traditional Ayurvedic practices. 

PMID- 25963258
TI  - TORC2 and eisosomes are spatially interdependent, requiring optimal level of
      phosphatidylinositol 4, 5-bisphosphate for their integrity.
AB  - The elucidation of the organization and maintenance of the plasma membrane has
      been sought due to its numerous roles in cellular function. In the budding yeast
      Saccharomyces cerevisiae, a novel paradigm has begun to emerge in the
      understanding of the distribution of plasma membrane microdomains and how they
      are regulated. We aimed to investigate the dynamic interdependence between the
      protein complexes eisosome and TORC2, representing microdomains MCC and MCT,
      respectively. In this study, we reveal that the eisosome organizer Pil1
      colocalizes with the MCT marker Avo2. Furthermore, we provide evidence that the
      formation of MCT is dependent on both eisosome integrity and adequate levels of
      the plasma membrane phosphoinositide PI(4,5)P2. Taken together, our findings
      indicate that TORC2, eisosomes, and PI(4,5)P2 exist in an interconnected
      relationship, which supports the emerging model of the plasma membrane. 

PMID- 25963259
TI  - Andrographolide suppresses epithelial mesenchymal transition by inhibition of
      MAPK signalling pathway in lens epithelial cells.
AB  - Epithelial mesenchymal transition (EMT) of lens epithelial cells (LECs) may
      contribute to the development of posterior capsular opacification (PCO), which
      leads to visual impairment. Andrographolide has been shown to have therapeutic
      potential against various cancers. However, its effect on human LECs is still
      unknown. The purpose of this study is to evaluate the effect of andrographolide
      on EMT induced by growth factors in the fetal human lens epithelial cell line
      (FHL 124). Initially the LECs were treated with growth factors (TGF-beta 2 and
      bFGF) to induce EMT. Subsequently these EMT-induced cells were treated with
      andrographolide at 100 and 500 nM concentrations for 24 h. Our results showed
      that FHL 124 cells treated with growth factors had a significant decrease in
      protein and m-RNA levels of epithelial markers pax6 and E-Cadherin. After
      administering andrographolide, these levels significantly increased. It was
      noticed that EMT markers alpha-SMA, fibronectin and collagen IV significantly
      decreased after treatment with andrographolide when compared to the other group.
      Treatment with andrographolide significantly inhibited phosphorylation of ERK and
      JNK. Cell cycle analysis showed that andrographolide did not arrest cells at
      G0/G1 or G2/M at tested concentrations. Our findings suggest that andrographolide
      helps sustain epithelial characteristics by modulating EMT markers and inhibiting
      the mitogen-activated protein kinase (MAPK) signalling pathway in LECs. Hence it
      can prove to be useful in curbing EMT-mediated PCO. 

PMID- 25963260
TI  - A hypomorphic Cbx3 allele causes prenatal growth restriction and perinatal energy
      homeostasis defects.
AB  - Mammals have three HP1 protein isotypes HP1 beta (CBX1), HP1 alpha (CBX3) and HP1
      alpha (CBX5) that are encoded by the corresponding genes Cbx1, Cbx3 and Cbx5.
      Recent work has shown that reduction of CBX3 protein in homozygotes for a
      hypomorphic allele (Cbx3hypo) causes a severe postnatal mortality with around 99
      percent of the homozygotes dying before weaning. It is not known what the causes
      of the postnatal mortality are. Here we show that Cbx3hypo/hypo conceptuses are
      significantly reduced in size and the placentas exhibit a haplo-insufficiency.
      Late gestation Cbx3hypo/hypo placentas have reduced mRNA transcripts for genes
      involved in growth regulation, amino acid and glucose transport. Blood vessels
      within the Cbx3hypo/hypo placental labyrinth are narrower than wild-type. Newborn
      Cbx3hypo/hypo pups are hypoglycemic, the livers are depleted of glycogen reserves
      and there is almost complete loss of stored lipid in brown adipose tissue (BAT).
      There is a 10-fold reduction in expression of the BAT-specific Ucp1 gene, whose
      product is responsible for nonshivering themogenesis. We suggest that it is the
      small size of the Cbx3hypo/hypo neonates, a likely consequence of placental
      growth and transport defects, combined with a possible inability to
      thermoregulate that causes the severe postnatal mortality. 

PMID- 25963261
TI  - Early postnatal exposure to lithium in vitro induces changes in AMPAR mEPSCs and
      vesicular recycling at hippocampal glutamatergic synapses.
AB  - Lithium is an effective mood stabilizer but its use is associated with many side
      effects. Electrophysiological recordings of miniature excitatory postsynaptic
      currents (mEPSCs) mediated by glutamate receptor AMPA-subtype (AMPARs) in
      hippocampal pyramidal neurons revealed that CLi (therapeutic concentration of 1
      mM lithium, from days in vitro 4-10) decreased the mean amplitude and mean
      rectification index (RI) of AMPAR mEPSCs. Lowered mean RI indicate that
      contribution of Ca2+ -permeable AMPARs in synaptic events is higher in CLi
      neurons (supported by experiments sensitive to Ca2+ -permeable AMPAR modulation).
      Co-inhibiting PKA, GSK-3 beta and glutamate reuptake was necessary to bring about
      changes in AMPAR mEPSCs similar to that seen in CLi neurons. FM1-43 experiments
      revealed that recycling pool size was affected in CLi cultures. Results from
      minimum loading, chlorpromazine treatment and hyperosmotic treatment experiments
      indicate that endocytosis in CLi is affected while not much difference is seen in
      modes of exocytosis. CLi cultures did not show the high KCl associated
      presynaptic potentiation observed in control cultures. This study, by calling
      attention to long-term lithium-exposure-induced synaptic changes, might have
      implications in understanding the side effects such as CNS complications
      occurring in perinatally exposed babies and cognitive dulling seen in patients on
      lithium treatment. 

PMID- 25963262
TI  - Functional and structural abnormalities associated with empathy in patients with
      schizophrenia: An fMRI and VBM study.
AB  - Empathy deficit is a core feature of schizophrenia which may lead to social
      dysfunction. The present study was carried out to investigate functional and
      structural abnormalities associated with empathy in patients with schizophrenia
      using functional magnetic resonance imaging (fMRI) and voxel-based morphometry
      (VBM). A sample of 14 schizophrenia patients and 14 healthy control subjects
      matched for age, sex and education were examined with structural highresolution
      T1-weighted MRI; fMRI images were obtained during empathy task in the same
      session. The analysis was carried out using SPM8 software. On behavioural
      assessment, schizophrenic patients (83.00+-29.04) showed less scores for sadness
      compared to healthy controls (128.70+-22.26) (p less than 0.001). fMRI results
      also showed reduced clusters of activation in the bilateral fusiform gyrus, left
      lingual gyrus, left middle and inferior occipital gyrus in schizophrenic subjects
      as compared to controls during empathy task. In the same brain areas, VBM results
      also showed reduced grey and white matter volumes. The present study provides an
      evidence for an association between structural alterations and disturbed
      functional brain activation during empathy task in persons affected with
      schizophrenia. These findings suggest a biological basis for social cognition
      deficits in schizophrenics. 

PMID- 25963263
TI  - Microalgae respond differently to nitrogen availability during culturing.
AB  - Variations in the exogenous nitrogen level are known to significantly affect the
      physiological status and metabolism of microalgae. However, responses of red,
      green and yellow-green algae to nitrogen (N) availability have not been compared
      yet. Porphyridium cruentum, Scenedesmus incrassatulus and Trachydiscus minutus
      were cultured in the absence of N in the medium and subsequent resupply of N to
      the starved cells. Culture growth and in-gel changes in isoenzyme pattern and
      activity of glutamate synthase, glutamate dehydrogenase, malate dehydrogenase,
      aspartate aminotransferase, superoxide dismutase, catalase, glutathione
      peroxidase and glutathione reductase were studied. The results demonstrated that
      the algae responded to the fully N-depleted and N-replete culture conditions by
      species-specific metabolic enzyme changes, suggesting differential regulation of
      both enzyme activity and cellular metabolism. Substantial differences in the
      activities of the antioxidant enzymes between N-depleted and N-replete cells of
      each species as well as between the species were also found. In the present work,
      besides the more general responses, such as adjustment of growth and
      pigmentation, we report on the involvement of specific metabolic and antioxidant
      enzymes and their isoforms in the mechanisms operating during N starvation and
      recovery in P. cruentum, T. minutus and S. incrassatulus. 

PMID- 25963264
TI  - Do seed VLCFAs trigger spongy tissue formation in Alphonso mango by inducing
      germination?
AB  - Spongy tissue is a physiological disorder in Alphonso mango caused by the
      inception of germination-associated events during fruit maturation on the tree,
      rendering the fruit inedible. Inter-fruit competition during active fruit growth
      is a major contributing factor for the disorder which leads to reduced fat
      content in spongy tissue affected fruits. This study was, therefore, carried out
      to determine the possible association between seed fats and ST formation. The
      study of the fat content during fruit growth showed that it increased gradually
      from 40 percent fruit maturity. At 70 percent maturity, however, there was a
      sudden increase of fat content of whole fruit, leading to acute competition and
      resulting in differential allocation of resources among developing fruits. As a
      result, the seed in spongy-tissue-affected mature ripe fruit showed a marked drop
      in the levels of fats and the two very long chain fatty acids (VLCFAs),
      tetracosanoic acid and hexacosanoic acid together with an increase of linolenic
      acid and a fall in oleic acid contents, which are known to be key determinants
      for the initiation of pre-germination events in seed. Subsequently, a rise in the
      level of cytokinin and gibberellins in ST seed associated with a fall in abscisic
      acid level clearly signalled the onset of germination. Concurrently, a
      significant reduction in the ratio of linolenic acid/linoleic acid in pulp led to
      the loss of membrane integrity, cell death and the eventual formation of spongy
      tissue. Based on the above, it is concluded that a significant reduction in the
      biosynthesis of VLCFAs in seeds during fruit growth might trigger pre-germination
      events followed by a cascade of biochemical changes in the pulp, leading to lipid
      peroxidation and membrane injury in pulp culminating in ST development. Thus,
      this study presents crucial experimental evidence to highlight the critical role
      played by VLCFAs in inducing ST formation in Alphonso mango during the pre
      harvest phase of fruit growth. 

PMID- 25963265
TI  - Declines of seagrasses in a tropical harbour, North Queensland, Australia, are
      not the result of a single event.
AB  - A recent paper inferred that all seagrass in Cairns Harbour, tropical north
      eastern Australia, had undergone 'complete and catastrophic loss' as a result of
      tropical cyclone Yasi in 2011. While we agree with the concern expressed, we
      would like to correct the suggestion that the declines were the result of a
      single climatic event and that all seagrass in Cairns Harbour were lost. Recent
      survey data and trend analysis from an on-ground monitoring program show that
      seagrasses in Cairns Harbour do remain, albeit at low levels, and the decline in
      seagrasses occurred over several years with cyclone Yasi having little additional
      impact. We have conducted annual on-ground surveys of seagrass distribution and
      the above-ground meadow biomass in Cairns Harbour and Trinity Inlet since 2001.
      This has shown a declining trend in biomass since a peak in 2004 and in area
      since it peaked in 2007. In 2012, seagrass area and above-ground biomass were
      significantly below the long-term (12 year) average but seagrass was still
      present. Declines were associated with regional impacts on coastal seagrasses
      from multiple years of above-average rainfall and severe storm and cyclone
      activity, similar to other nearby seagrass areas, and not as a result of a single
      event. 

PMID- 25963266
TI  - Mammalian gastrointestinal parasites in rainforest remnants of Anamalai Hills,
      Western Ghats, India.
AB  - Habitat fragmentation is postulated to be a major factor influencing infectious
      disease dynamics in wildlife populations and may also be responsible, at least in
      part, for the recent spurt in the emergence, or re-emergence, of infectious
      diseases in humans. The mechanism behind these relationships are poorly
      understood due to the lack of insights into the interacting local factors and
      insufficient baseline data in ecological parasitology of wildlife. Here, we
      studied the gastrointestinal parasites of nonhuman mammalian hosts living in 10
      rainforest patches of the Anamalai Tiger Reserve, India. We examined 349 faecal
      samples of 17 mammalian species and successfully identified 24 gastrointestinal
      parasite taxa including 1 protozoan, 2 trematode, 3 cestode and 18 nematode taxa.
      Twenty of these parasites are known parasites of humans. We also found that as
      much as 73% of all infected samples were infected by multiple parasites. In
      addition, the smallest and most fragmented forest patches recorded the highest
      parasite richness; the pattern across fragments, however, seemed to be less
      straightforward, suggesting potential interplay of local factors. 

PMID- 25963267
TI  - Analysis of humpback whale sounds in shallow waters of the Southeastern Arabian
      Sea: An indication of breeding habitat.
AB  - The primary objective of this work was to present the acoustical identification
      of humpback whales, detected by using an autonomous ambient noise measurement
      system, deployed in the shallow waters of the Southeastern Arabian Sea (SEAS)
      during the period January to May 2011. Seven types of sounds were detected. These
      were characteristically upsweeps and downsweeps along with harmonics. Sounds
      produced repeatedly in a specific pattern were referred to as phrases (PQRS and
      ABC). Repeated phrases in a particular pattern were referred to as themes, and
      from the spectrographic analysis, two themes (I and II) were identified. The
      variation in the acoustic characteristics such as fundamental frequency, range,
      duration of the sound unit, and the structure of the phrases and themes are
      discussed. Sound units were recorded from mid-January to mid-March, with a peak
      in February, when the mean SST is approx. 28 degree C, and no presence was
      recorded after mid-March. The temporal and thematic structures strongly determine
      the functions of the humpback whale song form. Given the use of song in the SEAS,
      this area is possibly used as an active breeding habitat by humpback whales
      during the winter season. 

PMID- 25963269
TI  - The substance P/NK-1 receptor system: NK-1 receptor antagonists as anti-cancer
      drugs.
AB  - The substance P (SP)/neurokinin (NK)-1 receptor system plays an important role in
      cancer. SP promotes the proliferation of tumour cells, angiogenesis and the
      migration of tumour cells. We review the involvement of SP, the NK-1 receptor and
      NK-1 receptor antagonists in cancer. Tumour cells overexpress NK-1 receptors,
      which are involved in their viability. This overexpression suggests the
      possibility of specific treatment against tumour cells using NK-1 receptor
      antagonists, thus promoting a considerable decrease in the side effects of the
      treatment. This strategy opens up new approaches for cancer treatment, since
      these antagonists, after binding to their molecular target, induce the death of
      tumour cells by apoptosis, exert an antiangiogenic action and inhibit the
      migration of tumour cells. The use of NK-1 receptor antagonists such as
      aprepitant (used in clinical practice) as antitumour agents could be a promising
      innovation. The value of aprepitant as an antitumour agent could be determined
      faster than for less wellknown compounds because many studies addressing its
      safety and characterization have already been completed. The NK-1 receptor may be
      a promising target in the treatment of cancer; NK-1 receptor antagonists could
      act as specific drugs against tumour cells; and these antagonists could be new
      candidate anti-cancer drugs. 

PMID- 25963270
TI  - Evolutionary change and phylogenetic relationships in light of horizontal gene
      transfer.
AB  - Horizontal gene transfer has, over the past 25 years, become a part of
      evolutionary thinking. In the present paper I discuss horizontal gene transfer
      (HGT) in relation to contingency, natural selection, evolutionary change speed
      and the Tree-of-Life endeavour, with the aim of contributing to the understanding
      of the role of HGT in evolutionary processes. In addition, the challenges that
      HGT imposes on the current view of evolution are emphasized. 

PMID- 25963268
TI  - Oxidation as an important factor of protein damage: Implications for Maillard
      reaction.
AB  - Protein oxidation, the process caused especially by reactive oxygen and nitrogen
      species, is thought to play a major role in various oxidative processes within
      cells and is implicated in the development of many human diseases. This review
      provides a brief overview of the protein oxidation with the emphasis on the types
      of oxidation (oxidation of protein backbone and amino acid residues side chains,
      site-specific metal-catalysed protein oxidation), oxidationdependent generation
      of protein hydroperoxides, carbonyl derivatives and protein-protein cross
      linkages. Nonenzymatic glycoxidation (also known as Maillard reaction) as an
      important factor of protein damage, consequences of oxidative protein impairment
      and related diseases as well as means of monitoring and assessment of protein
      modifications are discussed. 

PMID- 25963271
TI  - Insights from exome sequencing for endocrine disorders.
AB  - Whole-exome sequencing has emerged as a fast and effective tool for the
      elucidation of genetic defects underlying both rare and common human diseases.
      Increased availability and decreased costs of next-generation sequencing have
      enabled investigators to use this approach not only in individual patients with
      rare diseases, but also to screen large cohorts or populations for the genetic
      determinants of diseases. Within the field of endocrinology, exome sequencing has
      led to major advancements in our understanding of many disorders including
      adrenal disease, growth and puberty disorders and type 2 diabetes mellitus, as
      well as a multitude of rare genetic syndromes with prominent endocrine
      involvement. In this Review, we provide an overview of these new insights and
      discuss the role that exome sequencing is expected to have in endocrine research
      and future clinical practice. 

PMID- 25963272
TI  - Short-term and long-term effects of osteoporosis therapies.
AB  - Progress continues to be made in the development of therapeutics for fracture
      prevention. Bisphosphonates are now available orally and intravenously, often as
      inexpensive generics, and remain the most widely used interventions for
      osteoporosis. The major safety concern associated with the use of bisphosphonates
      is the development of femoral shaft stress fractures and, although rare, this
      adverse event affords the principal rationale for restricting bisphosphonate
      therapy to those individuals with femoral T-scores <-2.5, and for providing drug
      holidays in those individuals requiring therapy for >5 years. Newer
      antiresorptive therapies, in the form of denosumab and cathepsin K inhibitors,
      might increase efficacy and possibly circumvent some of the safety concerns
      associated with bisphosphonate use (for example, gastrointestinal and renal
      complications). The combination of teriparatide with antiresorptives markedly
      increases effects on BMD; new anabolic agents are also very promising in this
      regard. However, whether or not these changes in BMD translate into improved
      efficacy of fracture prevention remains to be determined. Vitamin D is important
      for the prevention of osteomalacia, but does not influence BMD or fracture risk
      in patients not deficient in vitamin D. The balance of risks and benefits of
      calcium supplementation is contentious, but patients should be encouraged to
      adhere to a balanced diet aimed at maintaining a healthy body weight.
      Consideration of a patient's risk of falling, and its mitigation, are also
      important. In this Review, I summarize the short-term and long-term effects of
      osteoporosis therapies. 

PMID- 25963274
TI  - An evaluation of nasal bone and aperture shape among three South African
      populations.
AB  - Reliable and valid population specific standards are necessary to accurately
      develop a biological profile, which includes an estimation of peer-reported
      social identification (Hefner, 2009). During the last 300 years, colonialism,
      slavery and apartheid created geographic, physical and social divisions of
      population groups in South Africa. The purpose of this study was to evaluate
      variation in nasal bone and aperture shape in a modern population of black,
      white, and coloured South Africans using standard craniometric variables and
      geometric morphometrics, namely general Procrustes and elliptical Fourier
      analyses. Fourteen standard landmarks were digitally recorded or computationally
      derived from 310 crania using a 3D coordinate digitizer for discriminant
      function, principal components and generalized Procrustes analyses. For
      elliptical Fourier analysis, outlines of the nasal aperture were generated from
      standardized photographs. All classification accuracies were better than chance;
      the lowest accuracies were for coloured and the highest accuracies were for white
      South Africans. Most difficulties arose in distinguishing coloured and black
      South African groups from each other. Generally, misclassifications were noted
      between the sexes within each group rather than among groups, which suggests that
      sex has less influence on nasal bone and aperture shape than ancestry.
      Quantifiable variation in shape of the nasal aperture region between white and
      non-white South African groups was observed. 

PMID- 25963273
TI  - Ca(2+) handling in isolated brain mitochondria and cultured neurons derived from
      the YAC128 mouse model of Huntington's disease.
AB  - We investigated Ca(2+) handling in isolated brain synaptic and non-synaptic
      mitochondria and in cultured striatal neurons from the YAC128 mouse model of
      Huntington's disease. Both synaptic and non-synaptic mitochondria from 2- and 12
      month-old YAC128 mice had larger Ca(2+) uptake capacity than mitochondria from
      YAC18 and wild-type FVB/NJ mice. Synaptic mitochondria from 12-month-old YAC128
      mice had further augmented Ca(2+) capacity compared with mitochondria from 2
      month-old YAC128 mice and age-matched YAC18 and FVB/NJ mice. This increase in
      Ca(2+) uptake capacity correlated with an increase in the amount of mutant
      huntingtin protein (mHtt) associated with mitochondria from 12-month-old YAC128
      mice. We speculate that this may happen because of mHtt-mediated sequestration of
      free fatty acids thereby increasing resistance of mitochondria to Ca(2+)-induced
      damage. In experiments with striatal neurons from YAC128 and FVB/NJ mice, brief
      exposure to 25 or 100 MUM glutamate produced transient elevations in cytosolic
      Ca(2+) followed by recovery to near resting levels. Following recovery of
      cytosolic Ca(2+), mitochondrial depolarization with FCCP produced comparable
      elevations in cytosolic Ca(2+), suggesting similar Ca(2+) release and,
      consequently, Ca(2+) loads in neuronal mitochondria from YAC128 and FVB/NJ mice.
      Together, our data argue against a detrimental effect of mHtt on Ca(2+) handling
      in brain mitochondria of YAC128 mice. We demonstrate that mutant huntingtin
      (mHtt) binds to brain synaptic and nonsynaptic mitochondria and the amount of
      mitochondria-bound mHtt correlates with increased mitochondrial Ca(2+) uptake
      capacity. We propose that this may happen due to mHtt-mediated sequestration of
      free fatty acids thereby increasing resistance of mitochondria to Ca(2+)-induced
      damage.

PMID- 25963275
TI  - Spectrophotometric analysis of color changes in teeth incinerated at increasing
      temperatures.
AB  - Color changes produced by histological alterations in burned teeth can provide
      conclusive forensic information on the temperature of exposure. The objective was
      to correlate heat-induced color changes in incinerated teeth with increases in
      temperature (to 1200 degrees C). Spectrophotometry was used to measure lightness,
      chromaticity (a* and b*), whiteness, and yellowness in 80 teeth heated at
      temperatures of 100, 200, 400, 600, 800, 1000, or 1200 degrees C for 60 min.
      Chromaticity a* was reduced at 100 degrees C and lightness at 200 and 400 degrees
      C, while chromaticity b* and yellowness were reduced at 400 and 600 degrees C.
      Higher temperatures (800, 1000, and 1200 degrees C) produced progressive
      increases in lightness and whiteness but reductions in chromaticity b* and
      yellowness. The accuracy of color values to determine the temperature of exposure
      was determined by Receiver Operating Characteristic analysis. High accuracy was
      shown by lightness, chromaticity b* and yellowness values for temperatures
      between 800 degrees  and 1200 degrees C, by whiteness for temperatures of 1000
      degrees  and 1200 degrees C, and by lightness for temperatures of 200 degrees 
      and 400 degrees C, with sensitivity and specificity values ranging from 90% to
      100%. According to these results, colorimetric analysis of incinerated teeth can
      be used to estimate the temperature of exposure with high accuracy, with
      lightness being the most useful variable.

PMID- 25963276
TI  - The use of craniofacial superimposition for disaster victim identification.
AB  - Skull-to-face comparison is utilised for human identification where there is a
      suspected identity and the usual methods of identification, such as DNA or dental
      comparison, are not possible or practical. This research aimed to compare the
      reliability of manual and computerised craniofacial superimposition techniques
      and to establish the application of these techniques for disaster victim
      identification, where there may be a large database of passport-style images,
      such as the MPUB Interpol database. Twenty skulls (10 females; 10 males) were
      utilised from the William Bass Skeletal Collection at the University of Tennessee
      and compared to face pools of 20 face photographs of similar sex, age and ethnic
      group. A traditional manual photographic method and a new 3D computer-based
      method were used. The results suggested that profile and three-quarter views of
      the ante-mortem face were the most valuable for craniofacial superimposition.
      However, the poor identification rate achieved using images in frontal view
      suggests that the MPUB Interpol database would not be optimal for disaster victim
      identification, and passport-style images do not provide enough distinguishing
      facial detail. This suggests that multiple ante-mortem images with a variety of
      facial expression should be utilised for identification purposes. There was no
      significant difference in success between the manual and computer methods. 

PMID- 25963277
TI  - Effects of Apelin on RAW264.7 cells under both normal and hypoxic conditions.
AB  - Macrophages are an important source of pro-inflammatory and pro-angiogenic
      factors, which can promote pathological processes involving inflammation and
      angiogenesis. This study investigated the effects of Apelin on macrophages under
      both normal and hypoxic conditions. Under normal culture conditions, Apelin down
      regulated the mRNA expression levels of monocyte chemotactic protein 1 (MCP1),
      monocyte chemotactic protein 3 (MCP3), macrophage inflammatory protein 1
      (MIP1alpha, MIP1beta), vascular endothelial growth factor A (VEGFA), Angiopoietin
      2 (Ang2) and tumor necrosis factor alpha (TNFalpha). The supernatant
      concentrations of MCP1, MCP3, MIP1alpha, MIP1beta, macrophage inflammatory
      protein 2 (MIP2) and TNFalpha proteins were significantly decreased in the Apelin
      treated group. Hypoxia induced profound up-regulations of the angiogenic,
      chemokine, and inflammatory factors at both the mRNA and protein levels. Apelin
      suppressed the hypoxia-induced increases in MCP1, MCP3, MIP2, MIP1beta and
      TNFalpha expression. The underlying mechanism of Apelin inhibit inflammation is
      regulating NF-kappaB/JNK signal pathway. Additionally, Apelin can protect
      macrophages from apoptosis and can enhance cell migration during hypoxia. And
      cleaved Caspase9/3 pathways were involved in Apelin inhibiting RAW264.7
      apoptosis. In conclusion, we showed the effect of Apelin on RAW264.7 macrophage
      under normal and hypoxic condition, which could further influence the
      angiogenesis and inflammation process that promoted by macrophages. 

PMID- 25963278
TI  - Dynamic intracellular localization of Dazl protein during Xenopus germline
      development.
AB  - Xenopus dazl encoding an RNA-binding protein has been identified as a component
      of the germ plasm and is involved in the migration and differentiation of the
      primordial germ cells (PGCs). Here, we investigated the intracellular
      localization of Dazl in germline cells throughout the lifetime of Xenopus. In
      early embryogenesis, Dazl was detected initially in the germ plasm and then
      translocated to a perinuclear region. Then, it was detected within the nucleus in
      PGCs. Dazl was observed only in the cytoplasm in PGCs when sex differentiation
      began in the gonads. Dazl was distributed in both the nucleus and cytoplasm of
      the primary oogonium and spermatogonium, but only in the cytoplasm of the
      secondary oogonium and spermatogonium. In spermatocytes, Dazl was distributed
      throughout cytoplasm and localized at the spindles and cytoplasm during meiosis.
      Then, it was detected as speckles in the nucleus in the round spermatid. The
      dynamic intracellular localization suggests that Dazl is a multifunctional
      protein regulating RNA metabolism required for Xenopus germline development. 

PMID- 25963279
TI  - 2014 President's plenary international psycho-oncology society: moving toward
      cancer care for the whole patient.
AB  - The International Psycho-oncology Society (IPOS) has just celebrated its 30th
      anniversary. The growth of psychosocial oncology has been exponential, and this
      relatively new field is becoming a core service that focuses on prevention,
      reducing the burden of cancer, and enhancing the quality of life from time of
      diagnosis, through treatment, survivorship, and palliative care. Looking back
      over the past 30 years, we see that cancer care globally has evolved to a new and
      higher standard. Today, 'cancer care for the whole patient' is being accomplished
      with an evidence-based model that addresses psychosocial needs and integrates
      psycho-oncology into the treatment and care of patients. The President's Plenary
      Session in Lisbon, Portugal, highlighted the IPOS Mission of promoting global
      excellence in psychosocial care of people affected by cancer through our
      research, public policy, advocacy, and education. The internationally endorsed
      IPOS Standard of Quality Cancer Care, for example, clearly states the necessity
      of integrating the psychosocial domain into routine care, and that distress
      should be measured as the sixth vital sign after temperature, blood pressure,
      pulse, respiratory rate, and pain. The plenary paper also discussed the global
      progress being made in Europe, North America, and Australia in providing quality
      cancer care for the whole patient. Collaborative partnerships between IPOS and
      organizations such as the European Partnership Action Against Cancer and the
      World Health Organization are essential in building capacity for the delivery of
      high-quality psycho-oncology services in the future.

PMID- 25963280
TI  - Aberrant germinal center formation, follicular T-helper cells, and germinal
      center B-cells were involved in chronic graft-versus-host disease.
AB  - Chronic graft-versus-host disease (cGVHD) is an important complication after
      allogeneic hematopoietic stem cell transplantation (HSCT). To define the roles of
      T-cells and B-cells in cGVHD, a murine minor histocompatibility complex
      mismatched HSCT model was used. Depletion of donor splenocyte CD4(+) T-cells and
      B220(+) B-cells alleviated cGVHD. Allogeneic recipients had significantly
      increased splenic germinal centers (GCs), with significant increases in
      follicular T-helper (Tfh) cells and GC B-cells. There were increased expressions
      in Tfh cells of inducible T-cell co-stimulator (ICOS), interleukin (IL)-4 and IL
      17, and in GC B-cells of B-cell activating factor receptor and ICOS ligand.
      Depletion of donor splenocyte CD4(+) T-cells abrogated aberrant GC formation and
      suppressed Tfh cells and GC B-cells. Interestingly, depletion of donor splenocyte
      B200(+) B-cells also suppressed Tfh cells in addition to GC B-cells. These
      results suggested that in cGVHD, both Tfh and GC B-cells were involved, and their
      developments were mutually dependent. The mammalian target of rapamycin (mTOR)
      inhibitor everolimus was effective in suppressing cGVHD, Tfh cells, and GC B
      cells, either as a prophylaxis or when cGVHD had established. These results
      implied that therapeutic targeting of both T-cells and B-cells in cGVHD might be
      effective. Signaling via mTOR may be another useful target in cGVHD. 

PMID- 25963281
TI  - Family carers' experience of caring for an older parent with severe and
      persistent mental illness.
AB  - While the burden of caring for older people with chronic medical illness and
      dementia has been well documented, considerably less is known about how carers
      develop the strength and resilience to sustain this important role with older
      family members with mental illness. The aim of the study was to understand the
      lived experience of primary caregivers of older people with severe and persistent
      mental illness, and to explore what, if anything, helps to sustain them in their
      caring role. An interpretative phenomenological analysis approach was adopted,
      and qualitative interviews were used with 30 primary caregivers. Two overarching
      themes, and related subthemes, were abstracted from the data. First, caring is a
      difficult and demanding responsibility. It affects carers adversely, emotionally,
      physically, socially, and financially, and their lifestyle in general. This is
      reflected in three subthemes: (i) physically and emotionally draining; (ii)
      grieving about the loss; (iii) and adverse effects on lifestyle and social
      relationships. Second, carers develop resilience in caring, which helps sustain
      them in their role, as illustrated in three subthemes: (i) caring as purposeful
      and satisfying; (ii) harnessing social support from others; and (iii)
      purposefully maintaining their own well-being. Community mental health nurses
      have a key role in assessing carers' needs and supporting them in their caring
      role. 

PMID- 25963282
TI  - Determination of kynurenic acid in rat cerebrospinal fluid by HPLC with
      fluorescence detection.
AB  - A sensitive HPLC method using fluorescence detection was developed to determine
      kynurenic acid (KYNA) level in rat cerebrospinal fluid (CSF). The method
      development was accomplished by screening different columns, optimizing zinc
      acetate concentration and determining the optimal HPLC flow rate. This method
      allowed direct injection of the CSF samples onto an Xselect C18 column and KYNA
      levels were measured fluorometrically by forming a fluorescent complex with zinc
      acetate that was delivered post-column. The limit of quantitation was 0.2 n m
      with 30 MUL injection, corresponding to 6 fmol (signal-to-noise ratio = 10). The
      improved sensitivity enabled the measurement of KYNA in naive and drug-treated
      rat CSF.

PMID- 25963283
TI  - Unusual Cause of Cord Compression-A Pressing Issue for Neurosurgeons.

PMID- 25963284
TI  - Autologous Hematopoietic Stem Cell Transplantation in Dialysis-Dependent Myeloma
      Patients.
AB  - BACKGROUND: We retrospectively analyzed our transplant database from July 2000 to
      June 2012 to identify myeloma patients who received autologous stem cell
      transplantation while dialysis-dependent. PATIENTS: 2091 patients underwent
      autologous high-dose therapy during this period. Twenty-four patients were
      dialysis-dependent. RESULTS: The 100-day and the 6, and 12-month treatment
      related mortality was 0%. Overall response rate was 92%. The median progression
      free survival and overall survival were 1.9 years and 3.8 years, respectively. A
      multivariate analysis was not performed because of the small sample size. Only 3
      patients became dialysis-independent after transplantation. Cardiac,
      gastrointestinal, genitourinary, infectious, neurologic, and pulmonary "all
      grade" toxicities were all higher in the melphalan 200 group versus < 200 group,
      however, none of them were statistically significant. CONCLUSION: Because of a
      lack of clear survival benefit with higher-dose melphalan and potential higher
      toxicity in this group, it is reasonable to use lower-dose melphalan in dialysis
      dependent myeloma patients.

PMID- 25963285
TI  - 1-23I-MIBG thyroid uptake: Implications for MIBG imaging of the heart.
AB  - BACKGROUND: 123I-MIBG has been widely used in patients with heart failure and
      neurological disorders. The patients are pre-treated with Lugol's oral solution
      or potassium perchlorate to prevent thyroid uptake of unlabeled 123I to limit the
      thyroid radiation exposure. However, despite the inhibition of the iodide pump,
      the thyroid is frequently visualized. The aim of this study was to study the
      pattern of thyroid uptake. METHODS: We reviewed the 123I-MIBG images of 57
      patients studied in three different centers in Italy for cardiac (n = 42) or
      neurological (n = 15) indications. They were imaged at 15 minutes and 4 hours
      after injection and in all patients, the thyroid was included in the imaging
      field of view. In 2 of the 3 centers, the patients were pre-treated with Lugol's
      oral solution and/or potassium perchlorate (group 1) but in the third center,
      they were not (group 2). The following imaging parameters were evaluated: heart
      to-mediastinum ratio (H/M), thyroid-to-mediastinum ratio (T/M) at 4 hours, and
      tracer wash out from the heart (HWO) and from the thyroid (TWO). RESULTS: In the
      cardiac patients, the HWO was 22.98 +/- 7.16% and TWO was 11.4 +/- 11.86% (P <
      .0001). The TWO was 12.2 +/- 13.1% in group 1 and 10.05 +/- 8.97% in group 2 (P =
      NS). In the neurological patients the HWO was 26 +/- 8.1% and the TWO was 20.32
      +/- 6.41 (P < .05). The difference in TWO was statistically significant (P < .01)
      between cardiac and neurological patients, whereas the HWO was not. The 4-hour
      H/M was 1.49 +/- 0.23 in cardiac patients vs 1.4 +/- 0.39 in neurological
      patients (P = NS). The 4-hour T/M was 1.33 +/- 0.3 in cardiac patients vs 1.15 +/
      0.13 in neurological patients (P < 0.05). CONCLUSION: The thyroid visualization
      in MIBG imaging is likely an expression of thyroid sympathetic innervation. The
      differences in TWO and T/M ratio in cardiac and neurological patients probably
      express differences in thyroid dopaminergic receptors. Thus, pre-treatment with
      potassium perchlorate or Lugol's solution may not be justified in patients
      undergoing 123I-MIBG imaging in whom the risk of side effects due to pre
      treatment could be higher than the risk due to thyroid radiation exposure.

PMID- 25963288
TI  - Association of Mitral Valve Prolapse With Infective Endocarditis Due to Viridans
      Group Streptococci.
AB  - Although patients with certain cardiac valve abnormalities have increased risk of
      infective endocarditis (IE), it is unknown whether these abnormalities are
      associated with specific pathogens in IE cases. We report a strong association
      between mitral valve prolapse and viridans group streptococcal IE in a population
      based cohort from Olmsted County, Minnesota. 

PMID- 25963289
TI  - Negative expression of PTEN identifies high risk for lymphatic-related metastasis
      in human esophageal squamous cell carcinoma.
AB  - The poor prognosis of esophageal squamous cell carcinoma (ESCC) is mainly
      attributed to higher lymphatic-related metastatic ability. Whether the loss of
      expression of the phosphatase and tensin homolog deleted on chromosome 10 (PTEN)
      is associated with lymphatic-related metastasis needs elucidation. In the present
      study, we assessed the mRNA and protein level of PTEN in ESCC by qRT-PCR and
      immunohistochemistry. The results showed PTEN mRNA level in tumors was
      significantly lower than that in corresponding non-tumor esophageal epitheliums
      (p<0.001), while 38 (51.4%) tumor samples were negative for expression of PTEN in
      ESCC tumors. Then the association between negative expression of PTEN and
      lymphatic-related metastasis (lymph node metastasis/3-year postoperative
      lymphatic metastatic recurrence) was evaluated. The proportion of PTEN-negative
      expression was significantly higher in positive lymph node metastasis (pN+) than
      that in negative lymph node metastasis (pN0) (p=0.021). The negative expression
      of PTEN was not an independent risk factor for the lymphatic recurrence rate in
      multivariate analysis (p=0.498), however, the lymphatic recurrence rate (60.5%)
      in PTEN-negative expression group was higher than that (36.1%) in PTEN-positive
      expression group (p=0.019). Furthermore, PTEN expression was stably silenced by
      lentiviral-vectored shRNA (Lenti-shRNA) in Eca109 (ESCC-derived cell line) to
      study functional effect of PTEN in vitro and in vivo. The laboratory study
      indicated increased cell proliferation, migration and invasion in vitro and more
      rapid growth rate of xenograft tumors in vivo after stable silencing of PTEN
      expression. Moreover, we proved that FAK/pFAK were not the main factors mediating
      the mechanism of metastasis in ESCC. In conclusion, negative expression of PTEN
      could be a useful biomarker to predict high risk for lymphatic-related metastasis
      in ESCC.

PMID- 25963290
TI  - Effect of Platelet-rich Fibrin on Healing of Apicomarginal Defects: A Randomized
      Controlled Trial.
AB  - INTRODUCTION: The purpose of this prospective, randomized controlled trial was to
      evaluate the healing outcomes of platelet-rich fibrin (PRF) in periapical
      surgeries involving apicomarginal defects and to compare these results with
      surgeries not using any guided tissue regeneration techniques. METHODS: Thirty
      patients with suppurative chronic apical periodontitis and apicomarginal
      communication were randomly assigned to either the PRF or the control group.
      Clinical and radiographic parameters including pocket depth (PD), clinical
      attachment level, gingival marginal position, size of periapical lesion, and
      percentage reduction of the periapical radiolucency were recorded at baseline and
      at an interval of 3 months for a period of 12 months. RESULTS: The overall
      success rate was 83.33%, with a success rate of 86.66% (13 of 15 teeth) for PRF
      group and 80% (12 of 15 teeth) for control group. Both the groups exhibited a
      significant reduction in PD, clinical attachment level, gingival marginal
      position, and size of periapical lesion at 12-month period. No significant
      differences were observed between the 2 groups for these parameters except PD,
      which showed a statistically significant reduction in the PRF group (P < .05).
      CONCLUSIONS: The adjunctive use of regenerative techniques may not promote
      healing of apicomarginal defects of endodontic origin.

PMID- 25963286
TI  - Chloroplast immunophilins.
AB  - Immunophilins occur in almost all living organisms. They are ubiquitously
      expressed proteins including cyclophilins, FK506/rapamycin-binding proteins, and
      parvulins. Their functional significance in vascular plants is mostly related to
      plant developmental processes, signalling, and regulation of photosynthesis.
      Enzymatically active immunophilins catalyse isomerization of proline imidic
      peptide bonds and assist in rapid folding of nascent proline-containing
      polypeptides. They also participate in protein trafficking and assembly of
      supramolecular protein complexes. Complex immunophilins possess various
      additional functional domains associated with a multitude of molecular
      interactions. A considerable number of immunophilins act as auxiliary and/or
      regulatory proteins in highly specialized cellular compartments, such as lumen of
      thylakoids. In this review, we present a comprehensive overview of so far
      identified chloroplast immunophilins that assist in specific assembly/repair
      processes necessary for the maintenance of efficient photosynthetic energy
      conversion.

PMID- 25963291
TI  - Are primary and secondary provoked vestibulodynia two different entities? A
      comparison of pain, psychosocial, and sexual characteristics.
AB  - INTRODUCTION: Provoked vestibulodynia (PVD) is suspected to be the most frequent
      cause of vulvodynia in premenopausal women. Based on the onset of PVD relative to
      the start of sexual experience, PVD can be divided into primary (PVD1) and
      secondary PVD (PVD2). Studies comparing these PVD subgroups are inconclusive as
      to whether differences exist in sexual and psychosocial functioning. AIM: The aim
      of this study was to compare the pain, sexual and psychosocial functioning of a
      large clinical and community-based sample of premenopausal women with PVD1 and
      PVD2. METHODS: A total of 269 women (n = 94 PVD1; n = 175 PVD2) completed
      measures on sociodemographics, pain, sexual, and psychosocial functioning. MAIN
      OUTCOME MEASURES: Dependent variables were the 0-10 pain numerical rating scale,
      McGill-Melzack Pain Questionnaire, Female Sexual Function Index, Global Measure
      of Sexual Satisfaction, Beck Depression Inventory-II, Painful Intercourse Self
      Efficacy Scale, Pain Catastrophizing Scale, State-Trait Anxiety Inventory Trait
      Subscale, Ambivalence over Emotional Expression Questionnaire, Hurlbert Index of
      Sexual Assertiveness, Experiences in Close Relationships Scale--Revised, and
      Dyadic Adjustment Scale-Revised. RESULTS: At first sexual relationship, women
      with PVD2 were significantly younger than women with PVD1 (P < 0.01). The average
      relationship duration was significantly longer in women with PVD2 compared with
      women with PVD1 (P < 0.01). Although women with PVD1 described a significantly
      longer duration of pain compared with women with PVD2 (P < 0.01), no significant
      subtype differences were found in pain intensity during intercourse. When
      controlling for the sociodemographics mentioned earlier, no significant
      differences were found in sexual, psychological, and relational functioning
      between the PVD subgroups. Nevertheless, on average, both groups were in the
      clinical range of sexual dysfunction and reported impaired psychological
      functioning. CONCLUSIONS: The findings show that there are no significant
      differences in the sexual and psychosocial profiles of women with PVD1 and PVD2.
      Results suggest that similar psychosocial and sex therapy interventions should be
      offered to both subgroups of PVD.

PMID- 25963292
TI  - The HEP Score: A Nomogram-Derived Hematoma Expansion Prediction Scale.
AB  - BACKGROUND: Identification of intracerebral hemorrhage (ICH) patients at risk of
      substantial hematoma expansion (SHE) could facilitate the selection of candidates
      likely to benefit from therapies aiming to minimize ICH growth. We aimed to
      develop a grading tool that can be quickly used during the hyperacute phase to
      predict the risk of SHE. METHODS: We reviewed data from 237 spontaneous ICH
      patients who had baseline head CT scan within 12 h of symptom onset and follow-up
      CT during the following 72 h. We performed logistic regression analyses to
      determine the predictors of SHE (defined as an absolute increase in ICH volume >6
      ml or an increase >33% on follow-up CT). We identified 6 predictors; each was
      assigned a point in the graphic interface of a nomogram which was used to
      construct a scoring system-The Hematoma Expansion Prediction (HEP) Score, varying
      from 0 to 18 points. We evaluated the ability of the model to predict the
      probability of SHE using c-statistics. RESULTS: SHE occurred in 74 patients
      (31.2%). The final model to predict SHE included 6 variables: time from onset to
      baseline CT (<3 vs. 3-12 h), history of dementia, current smoking, antiplatelet
      use, Glasgow Comma Scale score, and the presence of subarachnoid hemorrhage on
      baseline scan. The model had satisfactory discrimination ability with a bootstrap
      corrected c-index of 0.76 (95% CI 0.69-0.83) and good calibration. Patients with
      a total HEP score >3 were at greatest risk for SHE. CONCLUSIONS: We developed and
      internally validated a novel nomogram and an easy to use score which accurately
      predict the probability of SHE based on six easily obtainable parameters. This
      could be useful for treatment decision and stratification. External prospective
      validation of the HEP score is warranted before its application to other
      populations.

PMID- 25963293
TI  - Reliability and practicability of the straight leg raise test in children with
      cerebral palsy.
AB  - AIM: Preventing restrictions to lower limb movement is part of the treatment
      given to children with cerebral palsy (CP). Such restrictions can be assessed
      using the 'straight leg raise' (SLR) test. This study investigated the interrater
      reliability and practicability of the SLR test in children with CP. METHOD:
      Experienced physiotherapists examined 23 children with CP (6-18y; eight females,
      15 males) twice. The SLR hip range of motion (ROM) was measured using an
      electrogoniometer, and the test was rated based on sensitizing manoeuvres and
      biceps femoris muscle activity. Practicability was investigated by evaluating
      children's subjective feedback on the tolerable ROM. RESULTS: Intraclass
      correlation coefficients for the SLR hip ROM varied, ranging from 0.84 (95% CI
      0.61-0.93) to 0.93 (95% CI 0.87-0.96). Physiotherapists substantially agreed on
      SLR ratings (Cohen's kappa=0.73). Biceps femoris muscle activity decreased
      significantly with the release of tension on the sciatic nerve. All children were
      able to communicate the location and sensation of the maximally tolerated
      position. INTERPRETATION: The SLR test proved to be reliable and practicable in
      children with CP and might improve clinical reasoning processes. Lower limb
      movement restrictions in these children may partly be related to limitations in
      sciatic nerve mobility. Further studies should investigate if the SLR test could
      estimate activities in children with CP.

PMID- 25963294
TI  - Intensive care patients' perceptions of how their dignity is maintained: A
      phenomenological study.
AB  - AIM: The aim of the study was to acquire knowledge of what contributes to
      maintaining and promoting the dignity of intensive care patients. METHOD: The
      study takes a phenomenological approach, and the method of data collection is
      qualitative research interviews. The participants consist of seven former
      intensive care patients. The analysis was carried out by means of Giorgi's
      phenomenological analysis strategy. FINDINGS: Being seen and heard and having
      one's wishes and needs attended to are parts of dignified care. Personal and
      individual nursing was essential, as well as the extra involvement beyond what
      was expected. Being helpless and having to be cared for was unpleasant and
      degrading. The experience of being unable to speak could cause demeaning
      situations. Being met with respect was the essence of having one's dignity
      maintained and promoted. The sense of being treated as an object was the essence
      of experiences that inhibited dignity. CONCLUSION: The findings indicate that the
      intensive care patients' experience of having their dignity maintained in an
      intensive care unit is good, despite a high-tech, busy environment. There is also
      potential for improvement in several areas. Awareness, moral integrity and
      demeanour are central to dignified patient care from the perspective of intensive
      care patients.

PMID- 25963296
TI  - Effects of anosognosia and neuropsychiatric symptoms on the quality of life of
      patients with Alzheimer's disease: a 24-month follow-up study.
AB  - OBJECTIVES: Neuropsychiatric symptoms and anosognosia are known to influence the
      perceived quality of life of patients (QoL-p) with Alzheimer's disease (AD). This
      study analysed their impact on patient and caregiver ratings of QoL-p and how
      these ratings changed in relation to the severity of dementia. METHODS: A
      baseline sample of 221 patients and caregivers was followed up over 24 months.
      Instruments: Neuropsychiatric Inventory (NPI), Anosognosia Questionnaire-Dementia
      (AQ-D), Quality of life-Alzheimer's Disease (QoL-AD) and the Global Deterioration
      Scale (GDS). Longitudinal data were analysed using generalized linear models.
      RESULTS: In the multivariate analysis, greater anosognosia was always associated
      with higher ratings of QoL-p among patients, especially at 24 months (p < 0.001),
      and with more negative ratings among caregivers, especially at baseline (p <
      0.001). A higher total NPI score was associated with a more negative rating of
      QoL-p among caregivers (p < 0.001), and it also had a smaller negative effect on
      patients' self-ratings (p = 0.001). The neuropsychiatric symptoms (NPI)
      associated with a more negative view of QoL-p were depression, for patients' self
      ratings, and apathy and agitation for caregiver ratings. The discrepancy between
      patient and caregiver ratings increased in line with the severity of dementia.
      CONCLUSION: Neuropsychiatric symptoms had a similarly negative effect on the QoL
      p ratings of both patients and caregivers, whereas the effect of anosognosia
      differed according to the rater (positive for patients, negative for caregivers).

PMID- 25963295
TI  - Efficacy and safety of electroacupuncture with different acupoints for
      chemotherapy-induced nausea and vomiting: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Many patients experience nausea and vomiting during chemotherapy
      treatment. Evidence demonstrates that electroacupuncture is beneficial for
      controlling chemotherapy-induced nausea and vomiting (CINV). However, the
      acupoint or matching acupoint with the best efficacy for controlling CINV still
      remains unidentified. METHODS/DESIGN: This study consists of a randomized
      controlled trial (RCT) with four parallel arms: a control group and three
      electroacupuncture groups (one with Neiguan (PC6), one with Zhongwan (CV12), and
      one with both PC6 and CV12). The control group received standard antiemetic only,
      while the other three groups received electroacupuncture stimulation with
      different acupoints besides the standard antiemetic. The intervention is done
      once daily from the first day (day 1) to the fourth day (day 4) during
      chemotherapy treatment. The primary outcome measures include frequency of nausea,
      vomiting and retching. The secondary outcome measures are the grade of
      constipation and diarrhea, electrogastrogram, assessment of quality of life,
      assessment of anxiety and depression, and other adverse effects during the
      chemotherapy. Assessments are scheduled from one day pre-chemotherapy (day 0) to
      the fifth day of chemotherapy (day 5). Follow-ups are done from day 6 to day 21.
      DISCUSSION: The aim of this study is to evaluate the efficacy and safety of
      electro-acupuncture with different acupoints in the management of CINV. TRIAL
      REGISTRATION: The register number of randomized controlled trial is NCT02195908 .
      The date of registration was 21 July 2014.

PMID- 25963297
TI  - The effect of working time on the displacement of BiodentineTM beneath
      prefabricated stainless steel crown: a laboratory study.
AB  - OBJECTIVE: To investigate the displacement of BiodentineTM following cementation
      of stainless steel crowns (SSC) with glass-ionomer cement (GIC) on plastic
      deciduous teeth prepared for pulpotomy. METHODS: Twenty plastic teeth with
      prepared occlusal cavities were divided into four groups and had BiodentineTM
      placed as a mock pulpotomy agent. The pulp chamber was filled with freshly mixed
      BiodentineTM then a GIC-loaded SSC was seated on the tooth using a standardized
      seating force for periods of: 1 min (Group 1); 2 min (Group 2), 3 min (Group 3)
      and 6 min (Group 4) after mixing. After 24 h at 37 degrees C and 90% humidity,
      the crowns were sectioned mesio-distally and standardized digital photographs
      taken. Image analysis software was used to determine the ratio of the surface
      area of displaced BiodentineTM relative to the surface area of the pulp chamber.
      The thinnest section of the remaining BiodentineTM was measured. RESULTS: The
      lowest values of BiodentineTM displacement and the highest values of remaining
      BiodentineTM thickness were associated with Group 4. There were no significant
      differences between the results in Group 3 and Group 4. CONCLUSION: Within the
      limitations of this in vitro study, a GIC-loaded SSC can be seated on
      BiodentineTM placed into a pulp chamber 3 min after mixing.

PMID- 25963298
TI  - The complex interplay between cell-intrinsic and cell-extrinsic factors driving
      the evolution of chronic lymphocytic leukemia.
AB  - With the advent of next-generation sequencing, the mutational landscape of
      chronic lymphocytic leukemia (CLL) was rapidly unraveled with the discovery of
      recurrently mutated genes affecting key signaling pathways. Although the majority
      of these mutations are relatively infrequent at diagnosis (at least at the
      population-level) they tend to accumulate as the disease progresses or at
      relapse. Besides TP53 aberrations, several of these newly mutated genes have
      consistently been linked to shorter time to progression/treatment and poor
      overall survival (e.g. NOTCH1, SF3B1, BIRC3). These findings coupled with the
      diverse (sub)clonal evolution trajectory followed by CLL cells, at least in
      treated patients, alludes to their role as major subclonal driver events for
      disease progression. Together with the dependence of CLL cells on B-cell receptor
      (BcR) signaling and antigen stimulation, this reveals a disease within which both
      cell-intrinsic and cell-extrinsic factors conspire to fuel leukemogenesis, and we
      have only recently begun to understand their intricate interplay. This was
      further highlighted with the efficiency of new targeted therapy interfering with
      the microenvironment and in particular with BcR signaling. Further investigations
      will now be paramount in order to individualize treatment, to define optimal
      combination therapies and to integrate molecular characterization for response
      prediction, in this, as yet, incurable disease. 

PMID- 25963300
TI  - Surface plasmon resonance-based immunoassay for human C-reactive protein.
AB  - A rapid and highly-sensitive surface plasmon resonance (SPR)-based immunoassay
      (IA) has been developed and validated for detecting human C-reactive protein
      (CRP), a specific biomarker for inflammatory and metabolic disorders, and
      infections. The 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride
      (EDC)-activated protein A/G (Pr A/G) was diluted in 1% (v/v) 3
      aminopropyltriethoxysilane (APTES), dispensed on a KOH-treated gold (Au)-coated
      SPR chip, and incubated for 30 min. The Pr A/G functionalized Au SPR chip was
      then bound to anti-human CRP capture antibody (Ab), blocked with bovine serum
      albumin, and subsequently used for the detection of CRP. The highly-simplified
      oriented Ab immobilization strategy enabled the leach-proof binding of capture Ab
      in 5-fold shorter time than conventional procedures. The developed IA detected
      1.2-80 ng mL(-1) of CRP with a limit of detection (LOD) and a limit of
      quantification (LOQ) of 1.2 ng mL(-1) and 4.6 ng mL(-1), respectively. It
      detected CRP spiked in diluted human whole blood, serum and plasma as well as the
      CRP levels in the ethylenediaminetetraacetic acid (EDTA) plasma samples of
      patients with the same precision as the clinically-accredited analyzer-based IA
      and conventional CRP sandwich ELISA. The Ab-bound SPR chips stored at 4  degrees
      C retained their functional activity for 10 weeks, resulting in significant
      reduction in the overall analysis time. 

PMID- 25963299
TI  - Immune status of patients with inherited bone marrow failure syndromes.
AB  - Immune function abnormalities have been reported in patients with Fanconi anemia
      (FA), dyskeratosis congenita (DC) and, rarely, in Shwachman-Diamond syndrome
      (SDS), and Diamond-Blackfan anemia (DBA), but large systematic studies are
      lacking. We assessed immunological parameters in 118 patients with these
      syndromes and 202 unaffected relatives. We compared the results in patients with
      reference values, and with values in relatives after adjusting for age, sex,
      corticosteroid treatment, and severe bone marrow failure (BMF). Adult patients
      (>=18 years) with FA had significantly lower immunoglobulins (IgG, IgA and IgM),
      total lymphocytes, and CD4 T cells than reference values or adult relatives (P <
      0.001); children with FA had normal values. Both children and adults with FA had
      lower B- and NK cells (P < 0.01) than relatives or reference values. Patients
      with DC had essentially normal immunoglobulins but lower total lymphocytes than
      reference values or relatives, and lower T-, B-, and NK-cells; these changes were
      more marked in children than adults (P < 0.01). Most patients with DBA and SDS
      had normal immunoglobulins and lymphocytes. Lymphoproliferative responses, serum
      cytokine levels, including tumor necrosis factor-alpha and interferon-gamma, and
      cytokine levels in supernatants from phytohemagglutinin-stimulated cultures were
      similar across patient groups and relatives. Only patients with severe BMF,
      particularly those with FA and DC, had higher serum G-CSF and Flt3-ligand and
      lower RANTES levels compared with all other groups or relatives (P < 0.05).
      Overall, immune function abnormalities were seen mainly in adult patients with
      FA, which likely reflects their disease-related progression, and in children with
      DC, which may be a feature of early-onset severe disease phenotype.

PMID- 25963301
TI  - Communication during copulation in the sex-role reversed wolf spider Allocosa
      brasiliensis: Female shakes for soliciting new ejaculations?
AB  - Traditional studies on sexual communication have focused on the exchange of
      signals during courtship. However, communication between the sexes can also occur
      during or after copulation. Allocosa brasiliensis is a wolf spider that shows a
      reversal in typical sex roles and of the usual sexual size dimorphism expected
      for spiders. Females are smaller than males and they are the roving sex that
      initiates courtship. Occasional previous observations suggested that females
      performed body shaking behaviors during copulation. Our objective was to analyze
      if female body shaking is associated with male copulatory behavior in A.
      brasiliensis, and determine if this female behavior has a communicatory function
      in this species. For that purpose, we performed fine-scaled analysis of fifteen
      copulations under laboratory conditions. We video-recorded all the trials and
      looked for associations between female and male copulatory behaviors. The
      significant difference between the time before and after female shaking, in favor
      of the subsequent ejaculation is analyzed. We discuss if shaking could be acting
      as a signal to accelerate and motivate palpal insertion and ejaculation, and/or
      inhibiting male cannibalistic tendencies in this species. 

PMID- 25963303
TI  - Memory and executive functions in persons with type 2 diabetes: a meta-analysis.
AB  - Literature suggests that persons with type 2 diabetes mellitus (T2DM) are at risk
      for cognitive impairment, hence dementia. Common domains reported to be affected
      in those with T2DM are memory and executive functions. The extent of influence of
      T2DM on these domains has varied among studies. A systematic review and meta
      analysis was carried out to understand whether sub-domains contributed to the
      variations observed in published research. We searched 'PubMed', 'ScienceDirect',
      'SciVerseHub', 'Psychinfo', 'Proquest' 'Ebsco' and 'J-gate Plus' databases for
      published studies on cognition and T2DM among persons aged 50 years and older.
      Memory, executive functions and processing speed domain and sub-domain scores
      were extracted; effect sizes (Cohen's d) were calculated and analysed. Eight
      hundred seventeen articles were found. After various levels of filtering, 15
      articles met the inclusion criteria for quantitative analyses. The analyses
      indicated that in comparison to controls, persons with T2DM showed decrements in
      episodic memory (d = -0.51), logical memory (d = -0.24), sub-domain of executive
      functions which included phonemic fluency (d = -0.35) and cognitive flexibility
      (d = 0.52), and speed of processing (d = -0.22). We found no difference in the
      sub-domains of verbal short-term memory and working memory. The meta-analysis
      revealed a detrimental effect of T2DM on cognitive sub-domains, namely, episodic
      memory and cognitive flexibility. There was a trend for the logical memory,
      phonemic fluency and processing speed to be affected. The analysis indicates that
      T2DM is a detrimental factor on certain cognitive sub-domains, rendering the
      person vulnerable to subsequent dementia. Copyright (c) 2016 John Wiley & Sons,
      Ltd.

PMID- 25963302
TI  - Randomized clinical trial of mast cell inhibition in patients with a medium-sized
      abdominal aortic aneurysm.
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) is thought to develop as a result of
      inflammatory processes in the aortic wall. In particular, mast cells are believed
      to play a central role. The AORTA trial was undertaken to investigate whether the
      mast cell inhibitor, pemirolast, could retard the growth of medium-sized AAAs. In
      preclinical and clinical trials, pemirolast has been shown to inhibit antigen
      induced allergic reactions. METHODS: Inclusion criteria for the trial were
      patients with an AAA of 39-49 mm in diameter on ultrasound imaging. Among
      exclusion criteria were previous aortic surgery, diabetes mellitus, and severe
      concomitant disease with a life expectancy of less than 2 years. Included
      patients were treated with 10, 25 or 40 mg pemirolast, or matching placebo for 52
      weeks. The primary endpoint was change in aortic diameter as measured from
      leading edge adventitia at the anterior wall to leading edge adventitia at the
      posterior wall in systole. All ultrasound scans were read in a central imaging
      laboratory. RESULTS: Some 326 patients (mean age 70.8 years; 88.0 per cent men)
      were included in the trial. The overall mean growth rate was 2.42 mm during the
      12-month study. There was no statistically significant difference in growth
      between patients receiving placebo and those in the three dose groups of
      pemirolast. Similarly, there were no differences in adverse events. CONCLUSION:
      Treatment with pemirolast did not retard the growth of medium-sized AAAs.
      REGISTRATION NUMBER: NCT01354184 (https://www.clinicaltrials.gov).

PMID- 25963304
TI  - High-speed multiple-mode mass-sensing resolves dynamic nanoscale mass
      distributions.
AB  - Simultaneously measuring multiple eigenmode frequencies of nanomechanical
      resonators can determine the position and mass of surface-adsorbed proteins, and
      could ultimately reveal the mass tomography of nanoscale analytes. However,
      existing measurement techniques are slow (<1 Hz bandwidth), limiting throughput
      and preventing use with resonators generating fast transient signals. Here we
      develop a general platform for independently and simultaneously oscillating
      multiple modes of mechanical resonators, enabling frequency measurements that can
      precisely track fast transient signals within a user-defined bandwidth that
      exceeds 500 Hz. We use this enhanced bandwidth to resolve signals from multiple
      nanoparticles flowing simultaneously through a suspended nanochannel resonator
      and show that four resonant modes are sufficient for determining their individual
      position and mass with an accuracy near 150 nm and 40 attograms throughout their
      150-ms transit. We envision that our method can be readily extended to other
      systems to increase bandwidth, number of modes, or number of resonators. 

PMID- 25963305
TI  - In vitro characterisation of Span 65 niosomal formulations containing proteins.
AB  - Proteins can be encapsulated in niosomes as they are known to protect proteins
      against the surrounding environment. Niosomes of Span 65/cholesterol/pluronic F 
      127 were prepared by thin film hydration method. Insulin and lysozyme were chosen
      as model proteins. Niosomes were characterised for morphology by Transmission
      Electron Microscopy (TEM) and vesicles size using Dynamic Light Scattering. The
      entrapment efficiency of protein in niosomes was determined by complete vesicle
      disruption using 50:50% isopropanol:buf fer, followed by analysis of the
      resulting solutions by HPLC method. Thermal behaviour of the niosomes was
      investigated using Differential Scanning Calorimetry (DSC). Protection of
      proteins against simulated gastric fluid (SGF) and simulated intestinal fluid
      (SIF) were also assessed. The results showed that niosomes prepared with
      different molar ratios % of Span 65, cholesterol and pluronic F-127 successfully
      produced with insulin and lysozyme. For insulin containing niosomes, the ratio %
      of 64.7 (Span 65): 32.3 (cholesterol): 3.0 (pluronic F - 127) produced the
      highest protein encapsulation efficiency and the smallest vesicle size of 653.6
      nm. For lysozyme containing niosomes, the maximum protein encapsulation was found
      in 72.75/24.25/3.00% molar ratio of Span 65/cholesterol/pluronic F -127 niosomes
      with vesicle size of 627.3 nm. The release study of proteins from the niosomal
      preparations in simulated gastric fluid (SGF) and simulated intestinal fluid
      (SIF) revealed that insulin and lysozyme efflux from the niosomes is a biphasic
      process. The results indicate that Span 65 niosomes could be developed as
      controlled release dosage forms for delivery of peptides and proteins such as
      insulin and lysozyme.

PMID- 25963306
TI  - Improved Oral Bioavailability of Lacidipine Using Nanosuspension Technology:
      Inferior in vitro Dissolution and Superior in vivo Drug Absorption versus
      Lacipil(r).
AB  - Improved dissolution is a better way of increasing the oral absorption of
      lacidipine (LCDP) because it is a BCS II class drug. The purpose of this study is
      to improve the oral bioavailability of LCDP by applying nanosuspension
      technology. LCDP nanosuspensions were prepared by a hybrid method of
      microprecipitation and high pressure homogenization. The effects of the
      production parameters (shearing rate and time, the stabilizers and their
      concentrations, homogenization pressure and number of cycles) were investigated
      to optimize the preparation process. In vitro characterizations (X-ray powder
      diffraction, differential scanning calorimetry, scanning electron microscopy and
      dissolution measurement) were carried out and an oral pharmacokinetic study was
      performed in beagle dogs. LCDP was transformed into an amorphous state during the
      preparation process, and the mean particle size was about 714.0 +/- 12.7 nm. The
      dissolution rate of LCDP nanosuspensions was faster than that of physical
      mixtures, but slower than that of Lacipil(r) (the commercial tablet). Regarding
      the in vivo pharmacokinetics, the key pharmacokinetic parameters (Cmax and AUC0
      infinity) of the nanosuspensions were statistically significantly higher than
      those of both the commercial tablet and physical mixtures. So, this is an
      efficient drug delivery strategy to facilitate the oral administration of LCDP by
      using nanosuspension technology, and should be generally applicable to many
      poorly water-soluble drugs with dissolution rate-limited absorption. 

PMID- 25963307
TI  - Nanoparticles based on oleate alginate ester as curcumin delivery system.
AB  - Hydrophobic alginate derivative was prepared by the modification of alginate with
      methyl oleate. The synthesized oleate alginate ester (OAE) conjugate was
      characterized by FTIR and (1)HNMR analysis. Results of critical aggregation
      concentration (CAC) revealed that OAE conjugate had low CAC and was prone to form
      self-assembled nanoparticles in aqueous medium. Curcumin loaded OAE nanoparticles
      (Cur-OAE Nps) were developed by a simple sonication method and the
      physicochemical parameters of the nanoparticles such as zeta potential, size
      distribution and drug encapsulation were characterized. The results showed that
      zeta potential of the prepared nanoparticles was -55.4+/-0.91 mV and the average
      size was about 200 nm. A significant enhancement in aqueous solubility and
      stability of curcumin were observed after encapsulation into OAE nanoparticles.
      With the increase of curcumin concentration, loading efficiency increased but
      encapsulation efficiency decreased. The in vitro release profile exhibited
      significant sustained release pattern with initial burst release followed by a
      slower release over a period of one week. Cytotoxicity assay against MCF-7cells
      showed that Cur-OAE Nps had slow and continuous cytotoxic effect. Furthermore, in
      vitro cell uptake study revealed that cell uptake of curcumin from OAE
      nanoparticles was sustained and both were time and concentration dependent.
      Therefore, the developed Cur-OAE Nps might be promising candidates for curcumin
      delivery to cancer cells. 

PMID- 25963308
TI  - Anti-edema action of thyroid hormone in MCAO model of ischemic brain stroke:
      Possible association with AQP4 modulation.
AB  - The use of neuroprotective strategies to mitigate the fatal consequences of
      ischemic brain stroke is a focus of robust research activity. We have previously
      demonstrated that thyroid hormone (T3; 3,3',5-triiodo-l-thyronine) possesses
      neuroprotective and anti-edema activity in pre-stroke treatment regimens when
      administered as a solution or as a nanoparticle formulation. In this study we
      have extended our evaluation of thyroid hormone use in animal models of brain
      stroke. We have used both transient middle cerebral artery occlusion (t-MCAO) and
      permanent (p-MCAO) models of ischemic brain stroke. A significant reduction of
      tissue infarction and a concurrent decrease in edema were observed in the t-MCAO
      model of brain stroke. However, no benefit of T3 was observed in p-MCAO stroke
      setting. Significant improvement of neurological outcomes was observed upon T3
      treatment in t-MCAO mice. Further, we tested T2 (3,5-diiodo-l-thyronine) a
      natural deiodination metabolite of T3 in MCAO model of brain stroke. T2 potently
      decreased infarct size as well as edema formation. Additionally, we report here
      that T3 suppresses the expression of aquaporin-4 (AQP4) water channels which
      could be a likely mechanism of its anti-edema activity. Our studies provide
      evidence to stimulate clinical development of thyroid hormones for use in
      ischemic brain stroke. 

PMID- 25963309
TI  - Hyperemesis gravidarum and risk of cancer in offspring, a Scandinavian registry
      based nested case-control study.
AB  - BACKGROUND: Hyperemesis gravidarum is a serious condition affecting 0.8-2.3% of
      pregnant women and can be regarded as a restricted period of famine. Research
      concerning potential long-term consequences of the condition for the offspring,
      is limited, but lack of nutrition in-utero has been associated with chronic
      disease in adulthood, including some cancers. There is growing evidence that
      several forms of cancer may originate during fetal life. We conducted a large
      study linking the high-quality population-based medical birth- and cancer
      registries in Norway, Sweden and Denmark, to explore whether hyperemesis is
      associated with increased cancer risk in offspring. METHODS: A registry-based
      nested case-control study. Twelve types of childhood cancer were selected;
      leukemia, lymphoma, cancer of the central nervous system, testis, bone, ovary,
      breast, adrenal and thyroid gland, nephroblastoma, hepatoblastoma and
      retinoblastoma. Conditional logistic regression models were applied to study
      associations between hyperemesis and risk of childhood cancer, both all types
      combined and separately. Cancer types with five or more exposed cases were
      stratified by age at diagnosis. All analysis were adjusted for maternal age,
      ethnicity and smoking, in addition to the offspring's Apgar score, placental
      weight and birth weight. Relative risks with 95% confidence intervals were
      calculated. RESULTS: In total 14,805 cases and approximately ten controls matched
      on time, country of birth, sex and year of birth per case (147,709) were
      identified. None of the cancer types, analyzed combined or separately, revealed
      significant association with hyperemesis. When stratified according to age at
      diagnosis, we observed a RR 2.13 for lymphoma among adolescents aged 11-20 years
      ((95% CI 1.14-3.99), after adjustment for maternal ethnicity and maternal age, RR
      2.08 (95% CI 1.11-3.90)). The finding was not apparent when a stricter level of
      statistical significance was applied. CONCLUSIONS: The main finding of this paper
      is that hyperemesis does not seem to increase cancer risk in offspring. The
      positive association to lymphoma may be by chance and needs confirmation.

PMID- 25963310
TI  - Globalization and the health of Canadians: 'Having a job is the most important
      thing'.
AB  - BACKGROUND: Globalization describes processes of greater integration of the world
      economy through increased flows of goods, services, capital and people.
      Globalization has undergone significant transformation since the 1970s,
      entrenching neoliberal economics as the dominant model of global market
      integration. Although this transformation has generated some health gains, since
      the 1990s it has also increased health disparities. METHODS: As part of a larger
      project examining how contemporary globalization was affecting the health of
      Canadians, we undertook semi-structured interviews with 147 families living in
      low-income neighbourhoods in Canada's three largest cities (Montreal, Toronto and
      Vancouver). Many of the families were recent immigrants, which was another focus
      of the study. Drawing on research syntheses undertaken by the Globalization
      Knowledge Network of the World Health Organization's Commission on Social
      Determinants of Health, we examined respondents' experiences of three
      globalization-related pathways known to influence health: labour markets (and the
      rise of precarious employment), housing markets (speculative investments and
      affordability) and social protection measures (changes in scope and
      redistributive aspects of social spending and taxation). Interviews took place
      between April 2009 and November 2011. RESULTS: Families experienced an erosion of
      labour markets (employment) attributed to outsourcing, discrimination in
      employment experienced by new immigrants, increased precarious employment, and
      high levels of stress and poor mental health; costly and poor quality housing,
      especially for new immigrants; and, despite evidence of declining social
      protection spending, appreciation for state-provided benefits, notably for new
      immigrants arriving as refugees. Job insecurity was the greatest worry for
      respondents and their families. Questions concerning the impact of these
      experiences on health and living standards produced mixed results, with a
      majority expressing greater difficulty 'making ends meet,' some experiencing
      deterioration in health and yet many also reporting improved living standards. We
      speculate on reasons for these counter-intuitive results. CONCLUSIONS: Current
      trends in the three globalization-related pathways in Canada are likely to worsen
      the health of families similar to those who participated in our study.

PMID- 25963311
TI  - "It is not guaranteed that you will benefit": True but misleading?
AB  - BACKGROUND: Participants of early-phase intervention trials for serious
      conditions provide high estimates of likelihood of benefit, even when informed
      consent forms do not promise such benefits. However, some technically correct,
      negatively stated benefits statements-such as "it is not guaranteed that you will
      benefit"-could play a role in raising expectations of benefit because in ordinary
      English usage such statements denote a likely but not a certain-to-occur event.
      METHODS: An experimental online survey of 584 English-speaking adults recruited
      online. They were randomized to receive one of two benefit statements ("not
      guaranteed" vs "some but very small chance"), using a hypothetical scenario of an
      early-phase clinical trial testing an intervention to treat amyotrophic lateral
      sclerosis. We assessed respondents' willingness to consider participating in the
      amyotrophic lateral sclerosis trial, their estimates of likelihood of benefit,
      and their explanations for those estimates. RESULTS: The two arms did not differ
      in willingness to consider participation in the amyotrophic lateral sclerosis
      trial. Those receiving "not guaranteed" benefit statement had higher estimates of
      benefit than those receiving "some but very small chance" statement (35.7%
      (standard deviation 20.2) vs 28.3% (standard deviation 22.0), p < 0.0001). A
      total of 43% of all respondents chose expressions of positive sentiment (hope and
      need to stay positive) as explanations of their estimates; these respondents'
      estimates of benefit were higher than others but similar between the two arms.
      The effect of benefit statements was greatest among those who chose "Those are
      just the facts" as the explanation for their estimate (31.0% (standard deviation
      22.4%) in "not guaranteed" arm vs 18.9% (standard deviation 21.0%) in comparison
      arm, p = 0.008). CONCLUSION: The use of "not guaranteed" language in benefit
      statements, when compared to "small but very small chance" language, appeared to
      increase the perception of likelihood of benefit of entering an early-phase
      trial, especially among those who view their estimates of benefits as "facts."
      Such "no guarantee" benefit statements may be misleading and should not be used
      in informed consent forms.

PMID- 25963313
TI  - How can we assess the value of complex medical innovations in practice?
AB  - Rapid proliferation of medical innovations in the face of demographic changes and
      scarce resources is demanding a value-conscious entry of medical innovations into
      health care systems. An inquiry into value gains significance during the early
      diffusion phase of an innovation and becomes indispensable as the complexity of
      an innovation increases. In this editorial, we argue that a value assessment must
      pay attention to the social processes shaping the innovation's adoption and use,
      in particular, to the "promises" of the technology and actual "practices" with
      it. Promises and practices represent real-world value as they account for both
      outcomes and costs in practice. A systematic exploration of these loci of value,
      using insights from constructive technology assessment, enables us to make well
      informed decisions on complex medical technologies. 

PMID- 25963317
TI  - Intravesical dual PI3K/mTOR complex 1/2 inhibitor NVP-BEZ235 therapy in an
      orthotopic bladder cancer model.
AB  - NVP-BEZ235 is an inhibitor of both phosphatidylinositol 3-kinase (PI3K) and
      mammalian target of rapamycin complex 1/2 (mTORC1/2), and its antitumor activity
      is expected to be higher than that of mTORC1 inhibitors because it inhibits the
      upregulation of pAkt through mTORC2. We examined the efficacy of intravesical NVP
      BEZ235 therapy in the treatment of bladder cancer using an orthotopic bladder
      cancer model. The cytotoxic effects of various concentrations of NVP-BEZ235 in
      MBT-2 cells were examined using a WST assay. The expression of pAkt, pS6 and
      p4EBP1 was evaluated in MBT-2 cells treated with NVP-BEZ235 using western
      blotting. Orthotopic models were established by implanting MBT-2 cells into the
      bladders of female C3H/He mice. We assigned C3H/He mice to 2 groups: a control
      group treated with vehicle control (n=15), and a group intravesically
      administered 40 uM (18.78 mg/l) of NVP-BEZ235 (n=15). NVP-BEZ235 inhibited the
      viability of MBT-2 cells in a dose-dependent manner. Furthermore, the expression
      of pAkt, pS6, and p4EBP1 was inhibited in NVP-BEZ235-treated MBT-2 cells. Bladder
      weights were significantly lower in the NVP-BEZ235-treated group than in the
      control group (P<0.05). An analysis of the tumor tissues revealed that the NVP
      BEZ235 treatment strongly reduced pAkt, pS6 and p4EBP1 levels. An
      immunohistochemical analysis showed that NVP-BEZ235 significantly inhibited the
      expression of pS6. Intravesically administered NVP-BEZ235 exerted significant
      antitumor effects in the orthotopic bladder cancer model by inhibiting the
      PI3K/Akt/mTOR pathway. The intravesical instillation of a dual PI3K/mTORC1/2
      inhibitor may represent a novel therapy for the treatment of bladder cancer.

PMID- 25963314
TI  - The Influence of Aconitum carmichaelii Debx. on the Pharmacokinetic
      Characteristics of Main Components in Rheum palmatum L.
AB  - Rhei Radix et Rhizoma was one of the commonly used traditional Chinese medicines,
      and the compatibility of Rhei Radix et Rhizoma and Aconiti Lateralis Radix
      Praeparata was the basic herb pair applied in many Chinese traditional
      prescription. Rhubarb anthraquinones were the main bioactive materials of Rhei
      Radix et Rhizoma. To elucidate the compatibility of Rhei Radix et Rhizoma and
      Aconiti Lateralis Radix Praeparata, the pharmacokinetics of rhubarb
      anthraquinones as the main marker constituents were investigated. In the present
      study, pharmacokinetic differences of rhubarb anthraquinones were detected after
      oral administration of extract of Rheum palmatum L. and compatibility with
      Aconitum carmichaelii Debx. After oral administration, no difference of peak time
      can be found for anthraquinones between rhubarb group and compatibility group.
      But Cmax and area under the curve of aloe-emodin, emodin and chrysophanol in
      compatibility group were significantly higher than that in rhubarb group.
      Although the Cmax of rhein in compatibility group was much lower than that in
      rhubarb group, the area under the curve value was similar in two groups. The
      clearance and t1/2 of rhubarb anthraquinone were also changed after
      compatibility. The change of pharmacokinetics characteristics of rhubarb
      anthraquinone after compatibility may be caused by the drug-drug interaction
      medicated by chemical reaction and cytochromes P450.

PMID- 25963318
TI  - Microsphere skimming in the porcine coronary arteries: Implications for flow
      quantification.
AB  - Particle skimming is a phenomenon where particles suspended in fluid flowing
      through vessels distribute disproportionately to bulk fluid volume at junctions.
      Microspheres are considered a gold standard of intra-organ perfusion measurements
      and are used widely in studies of flow distribution and quantification. It has
      previously been hypothesised that skimming at arterial junctions is responsible
      for a systematic over-estimation of myocardial perfusion from microspheres at the
      subendocardium. Our objective is to integrate coronary arterial structure and
      microsphere distribution, imaged at high resolution, to test the hypothesis of
      microsphere skimming in a porcine left coronary arterial (LCA) network. A
      detailed network was reconstructed from cryomicrotome imaging data and a
      Poiseuille flow model was used to simulate flow. A statistical approach using
      Clopper-Pearson confidence intervals was applied to determine the prevalence of
      skimming at bifurcations in the LCA. Results reveal that microsphere skimming is
      most prevalent at bifurcations in the larger coronary arteries, namely the
      epicardial and transmural arteries. Bifurcations at which skimming was identified
      have significantly more asymmetric branching parameters. This finding suggests
      that when using thin transmural segments to quantify flow from microspheres, a
      skimming-related deposition bias may result in underestimation of perfusion in
      the subepicardium, and overestimation in the subendocardium. 

PMID- 25963319
TI  - Association of Exposure to Bisphenol A and Incidence of Cardiovascular Disease
      and Hypertension.

PMID- 25963312
TI  - The role of interleukin-18 in glioblastoma pathology implies therapeutic
      potential of two old drugs-disulfiram and ritonavir.
AB  - Based on reporting in the last several years, an impressive but dismal list of
      cytotoxic chemotherapies that fail to prolong the median overall survival of
      patients with glioblastoma has prompted the development of treatment protocols
      designed to interfere with growth-facilitating signaling systems by using non
      cytotoxic, non-oncology drugs. Recent recognition of the pro-mobility stimulus,
      interleukin-18, as a driver of centrifugal glioblastoma cell migration allows
      potential treatment adjuncts with disulfiram and ritonavir. Disulfiram and
      ritonavir are well-tolerated, non-cytotoxic, non-oncology chemotherapeutic drugs
      that are marketed for the treatment of alcoholism and human immunodeficiency
      virus (HIV) infection, respectively. Both drugs exhibit an interleukin-18
      inhibiting function. Given the favorable tolerability profile of disulfiram and
      ritonavir, the unlikely drug-drug interaction with temozolomide, and the poor
      prognosis of glioblastoma, trials of addition of disulfiram and ritonavir to
      current standard initial treatment of glioblastoma would be warranted. 

PMID- 25963315
TI  - Dinoflagellate Gene Structure and Intron Splice Sites in a Genomic Tandem Array.
AB  - Dinoflagellates are one of the last major lineages of eukaryotes for which little
      is known about genome structure and organization. We report here the sequence and
      gene structure of a clone isolated from a cosmid library which, to our knowledge,
      represents the largest contiguously sequenced, dinoflagellate genomic, tandem
      gene array. These data, combined with information from a large transcriptomic
      library, allowed a high level of confidence of every base pair call. This degree
      of confidence is not possible with PCR-based contigs. The sequence contains an
      intron-rich set of five highly expressed gene repeats arranged in tandem. One of
      the tandem repeat gene members contains an intron 26,372 bp long. This study
      characterizes a splice site consensus sequence for dinoflagellate introns. Two to
      nine base pairs around the 3' splice site are repeated by an identical two to
      nine base pairs around the 5' splice site. The 5' and 3' splice sites are in the
      same locations within each repeat so that the repeat is found only once in the
      mature mRNA. This identically repeated intron boundary sequence might be useful
      in gene modeling and annotation of genomes.

PMID- 25963316
TI  - Antithrombotic Regimens for Patients Taking Oral Anticoagulation After Coronary
      Intervention: A Meta-analysis of 16 Clinical Trials and 9,185 Patients.
AB  - The optimal antithrombotic regimen remains controversial in patients taking oral
      anticoagulation (OAC) undergoing coronary stenting. This study sought to compare
      efficacy and safety outcomes of triple therapy (OAC, aspirin, and clopidogrel) vs
      dual therapy (clopidogrel with aspirin or OAC) in these patients. We hypothesize
      OAC plus clopidogrel could be the optimal regimen for patients with indications
      for OAC receiving stent implantation. Medline, the Cochrane Library, and other
      Internet sources were searched for clinical trials comparing the efficacy and
      safety of triple vs dual therapy for patients taking OAC after coronary stenting.
      Sixteen eligible trials including 9185 patients were identified. The risks of
      major adverse cardiac events (odds ratio [OR]: 1.06, 95% confidence interval
      [CI]: 0.82-1.39, P = 0.65), all-cause mortality (OR: 0.98, 95% CI: 0.76-1.27, P =
      0.89), myocardial infarction (OR: 1.01, 95% CI: 0.77-1.31, P = 0.97), and stent
      thrombosis (OR: 0.91, 95% CI: 0.49-1.69, P = 0.75) were similar between triple
      and dual therapy. Compared with dual therapy, triple therapy was associated with
      a reduced risk of ischemic stroke (OR: 0.57, 95% CI: 0.35-0.94, P = 0.03) but
      with higher major bleeding (OR: 1.52, 95% CI: 1.11-2.10, P = 0.01) and minor
      bleeding (OR: 1.59, 95% CI: 1.05-2.42, P = 0.03). Subgroup analysis indicated
      there were similar ischemic stroke and major bleeding outcomes between triple
      therapy and therapy with OAC plus clopidogrel. Treatment with OAC and clopidogrel
      was associated with similar efficacy and safety outcomes compared with triple
      therapy. Triple therapy could be replaced by OAC plus clopidogrel without any
      concern about additional risk of thrombotic events. 

PMID- 25963320
TI  - Clinical use of insulin degludec.
AB  - The limitations of current basal insulin preparations include concerns related to
      their pharmacokinetic and pharmacodynamic properties, hypoglycaemia, weight gain,
      and perception of management complexity, including rigid dosing schedules.
      Insulin degludec (IDeg) is a novel basal insulin with improved pharmacokinetic
      and pharmacodynamic properties compared to insulin glargine (IGlar) including a
      long half-life of ~25 h and a duration of action >42 h at steady state, providing
      a flat and stable blood glucose-lowering effect when injected once daily.
      Evidence from phase 3a clinical trials with a treat-to-target design in patients
      with type 1 and type 2 diabetes has shown that IDeg has similar efficacy to
      IGlar, with a 9% and 26% reduction in risk of overall and nocturnal
      hypoglycaemia, respectively (in the pooled population) during the entire
      treatment period, and a 16% and 32% reduction during the maintenance period,
      respectively. Given its pharmacodynamic properties, IDeg offers a broad dosing
      window, allowing for flexible dose administration, if required. Two different
      formulations of IDeg are available (100 units/mL [U100] and 200 units/mL), the
      latter providing the same IDeg dose as the U100 formulation in half the injection
      volume. The unique pharmacokinetic profile of IDeg facilitates glycaemic control
      while minimising the risk of nocturnal hypoglycaemia.

PMID- 25963321
TI  - Dengue severity: a key determinant of underreporting.

PMID- 25963322
TI  - Sphincterotomy with Large Balloon to Extract Common Bile Duct Stones: Sometimes
      It Is Better to Get an "Incomplete".

PMID- 25963323
TI  - Vitamin-D Deficiency Is Associated with Gallbladder Stasis Among Pregnant Women.
AB  - BACKGROUND: Pregnant women are at increased risk of gallbladder (GB) stasis, an
      important risk factor for gallstones (GS). In non-pregnant women, Vitamin-D
      deficiency (VDD) is associated with GB stasis, which improves on supplementation.
      Relationship of VDD with GB stasis among pregnant women is not known. METHODS:
      This is a prospective study in tertiary care centre. Consecutive healthy pregnant
      women (12-16 weeks gestation) were enrolled. Serum 25(OH) vitamin-D was
      estimated, and levels <20 ng ml(-1) were considered as VDD. Risk factors and
      clinical features of VDD were assessed. Gallbladder ejection fraction (GBEF) was
      assessed by ultrasound after a standard fatty meal, and <40 % was defined as
      stasis. Statistical analysis was performed to assess relationship of GB stasis
      and vitamin-D levels and identify factors associated with VDD. KEY RESULTS:
      Median serum vitamin-D in 304 women was 7.9 ng ml(-1) (IQR 5.7, 12). VDD
      afflicted 92 % of them. Women with VDD more often had GB stasis (20 % vs 0 %; p =
      0.015) and had lower GBEF [53.7 +/- 17 % vs 59 +/- 10 %; p = 0.026] compared to
      those with normal vitamin-D. GBEF showed positive correlation with vitamin-D
      levels (r = 0.117; p = 0.042). Risk factors for low vitamin-D levels were urban
      residence (p = 0.001), lower sun-exposure time (p = 0.005), limited skin exposure
      (p < 0.001), higher BMI (p = 0.05) and higher socioeconomic status (p = 0.02).
      Vitamin-D deficiency was associated with low serum calcium (rho = 0.457; p <
      0.001). CONCLUSIONS: Vitamin D deficiency is highly prevalent among pregnant
      Indian women. It is associated with GB stasis and lower GBEF. The risk factors
      for VDD were reduced sun exposure, inadequate dietary intake and urban lifestyle.

PMID- 25963324
TI  - Brain-Derived Neurotrophic Factor Contributes to Colonic Hypermotility in a
      Chronic Stress Rat Model.
AB  - BACKGROUND: Brain-derived neurotrophic factor (BDNF) has prokinetic effects on
      gut motility and is increased in the colonic mucosa of irritable bowel syndrome.
      AIMS: We aimed to investigate the possible involvement of BDNF in stress-induced
      colonic hypermotility. METHODS: Male Wistar rats were exposed to daily 1-h water
      avoidance stress (WAS) or sham WAS for 10 consecutive days. The presence of BDNF
      and substance P (SP) in the colonic mucosa was determined using enzyme
      immunoassay kits. Immunohistochemistry and western blotting were performed to
      assess the expression of BDNF and its receptor, TrkB. The contractions of muscle
      strips were studied in an organ bath system. RESULTS: Repeated WAS increased the
      fecal pellet expulsion and spontaneous contractile activities of the colonic
      muscle strips. Both BDNF and SP in the colonic mucosa were elevated following
      WAS. Immunohistochemistry revealed the presence of BDNF and TrkB in the mucosa
      and myenteric plexus. BDNF and TrkB were both up-regulated in colon devoid of
      mucosa and submucosa from the stressed rats compared with the control. BDNF
      pretreatment caused an enhancement of the SP-induced contraction of the circular
      muscle (CM) strips. TrkB antibody significantly inhibited the contraction of the
      colonic muscle strips and attenuated the excitatory effects of SP on contractions
      of the CM strips. Repeated WAS increased the contractile activities of the CM
      strips induced by SP after BDNF pretreatment, and this effect was reversed by
      TrkB antibody. CONCLUSIONS: The colonic hypermotility induced by repeated WAS may
      be associated with the increased expression of endogenous BDNF and TrkB. BDNF may
      have potential clinical therapeutic use in modulating gut motility.

PMID- 25963325
TI  - My Well-Being in My Own Hands: Experiences of Beneficial Recovery During Burnout
      Rehabilitation.
AB  - PURPOSE: To explore how burnout rehabilitation clients experienced their recovery
      from burnout and what they found beneficial in rehabilitation. SUBJECTS: Twelve
      clients whose burnout levels had declined during rehabilitation were interviewed
      at the end of the second period of the rehabilitation course. METHODS: Semi
      structured interviews comprised the main material of the study and were analysed
      by content analysis. In addition, the Bergen Burnout Indicator (BBI-15) was used
      to measure the reduction in burnout levels. RESULTS: The analysis yielded a
      single overarching theme, My well-being in my own hands, and four categories. The
      overarching theme describes the overall process of recovery and the revelation
      experienced by clients that they are in charge of their own well-being. The
      process starts with Support from rehabilitation professionals, the client group
      and family or friends. The categories Awareness and Approval refer to specific
      changes in the attitude towards and recognition of one's needs and limits. The
      category Regained joy describes the culmination of the recovery process
      manifested in different spheres of life. CONCLUSIONS: The rehabilitation course
      proved particularly beneficial for individuals suffering from burnout. The
      accumulation of support, awareness and approval led to a revival of joy in life
      and greater perceived control over one's well-being.

PMID- 25963326
TI  - Electro-mechanical anisotropy of phosphorene.
AB  - The applied uniaxial stress can break the original symmetry of a material,
      providing an experimentally feasible way to alter material properties. Here, we
      explore the effects of uniaxial stress along an arbitrary direction on mechanical
      and electronic properties of phosphorene, showing the enhancement of inherent
      anisotropy. Basic physical quantities including Young's modulus, Poisson's ratio,
      band gap, and effective carrier masses under external stress are all computed
      from first principles using density functional theory, while the final results
      are presented in compact analytical forms. 

PMID- 25963328
TI  - Anti-Obesity Pharmacotherapy: The Intercontinental Regulatory Divide.

PMID- 25963329
TI  - Strategies to prevent and reverse liver fibrosis in humans and laboratory
      animals.
AB  - Liver fibrosis results from chronic damage to the liver in conjunction with
      various pathways and is mediated by a complex microenvironment. Based on clinical
      observations, it is now evident that fibrosis is a dynamic, bidirectional process
      with an inherent capacity for recovery and remodeling. The major mechanisms
      involved in liver fibrosis include the repetitive injury of hepatocytes, the
      activation of the inflammatory response after injury stimulation, and the
      activation and proliferation of hepatic stellate cells (HSCs), which represents
      the major extracellular matrix (ECM)-producing cells, stimulated by hepatocyte
      injury and inflammation. The microenvironment in the liver is synergistically
      regulated abnormal ECM deposition, scar formation, angiogenesis, and
      fibrogenesis. Moreover, recent studies have clarified novel mechanism in fibrosis
      such as epigenetic regulation of HSCs, the leptin and PPARgamma pathways, the
      coagulation system, and even autophagy. Uncovering the mechanisms of liver
      fibrogenesis provides a basis to develop potential therapies to reverse and treat
      the fibrotic response, thereby improving the outcomes of patients with chronic
      liver disease. Although both scientific and clinical challenges remain, emerging
      studies attempt to reveal the ideal anti-fibrotic drug that could be easily
      delivered to the liver with high specificity and low toxicity. This review
      highlights the mechanisms, including novel pathways underlying fibrogenesis that
      may be translated into preventive and treatment strategies, reviews both current
      and novel agents that target specific pathways or multiple targets, and discusses
      novel drug delivery systems such as nanotechnology that can be applied in the
      treatment of liver fibrosis. In addition, we also discuss some current treatment
      strategies that are being applied in animal models and in clinical trials. 

PMID- 25963330
TI  - St. John's wort treatment in women bears risks beyond pharmacokinetic drug
      interactions.
AB  - We analyzed adverse events in a clinical phase I trial to assess dose-dependent
      metabolic effects of St. John's wort co-administered with rifampicin in 12
      healthy volunteers. Within 3-6 days after increasing the St. John's wort dose
      from 300 to 600 mg TID, five of six female participants developed ambient
      temperature-dependent allodynia and paresthesia in sun-exposed areas (back of the
      hands and perioral and nasal area). Aggravation of symptoms resulted in
      persistence of paresthesia and phototoxic erythrodermia. None of the male
      participants showed any of these effects. Gender, duration of treatment, dose,
      and solar exposure seem to be extrinsic and host factors facilitating St. John's
      wort-induced neuropathy. The risk to develop this adverse effect is almost
      exclusively present in women.

PMID- 25963327
TI  - Advances in NSAID development: evolution of diclofenac products using
      pharmaceutical technology.
AB  - Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) of the phenylacetic
      acid class with anti-inflammatory, analgesic, and antipyretic properties.
      Contrary to the action of many traditional NSAIDs, diclofenac inhibits
      cyclooxygenase (COX)-2 enzyme with greater potency than it does COX-1. Similar to
      other NSAIDs, diclofenac is associated with serious dose-dependent
      gastrointestinal, cardiovascular, and renal adverse effects. Since its
      introduction in 1973, a number of different diclofenac-containing drug products
      have been developed with the goal of improving efficacy, tolerability, and
      patient convenience. Delayed- and extended-release forms of diclofenac sodium
      were initially developed with the goal of improving the safety profile of
      diclofenac and providing convenient, once-daily dosing for the treatment of
      patients with chronic pain. New drug products consisting of diclofenac potassium
      salt were associated with faster absorption and rapid onset of pain relief. These
      include diclofenac potassium immediate-release tablets, diclofenac potassium
      liquid-filled soft gel capsules, and diclofenac potassium powder for oral
      solution. The advent of topical formulations of diclofenac enabled local
      treatment of pain and inflammation while minimizing systemic absorption of
      diclofenac. SoluMatrix diclofenac, consisting of submicron particles of
      diclofenac free acid and a proprietary combination of excipients, was developed
      to provide analgesic efficacy at reduced doses associated with lower systemic
      absorption. This review illustrates how pharmaceutical technology has been used
      to modify the pharmacokinetic properties of diclofenac, leading to the creation
      of novel drug products with improved clinical utility.

PMID- 25963331
TI  - Common genetic variation and schizophrenia polygenic risk influence
      neurocognitive performance in young adulthood.
AB  - Neurocognitive abilities constitute complex traits with considerable
      heritability. Impaired neurocognition is typically observed in schizophrenia
      (SZ), whereas convergent evidence has shown shared genetic determinants between
      neurocognition and SZ. Here, we report a genome-wide association study (GWAS) on
      neuropsychological and oculomotor traits, linked to SZ, in a general population
      sample of healthy young males (n = 1079). Follow-up genotyping was performed in
      an identically phenotyped internal sample (n = 738) and an independent cohort of
      young males with comparable neuropsychological measures (n = 825). Heritability
      estimates were determined based on genome-wide single-nucleotide polymorphisms
      (SNPs) and potential regulatory effects on gene expression were assessed in human
      brain. Correlations with general cognitive ability and SZ risk polygenic scores
      were tested utilizing meta-analysis GWAS results by the Cognitive Genomics
      Consortium (COGENT) and the Psychiatric Genomics Consortium (PGC-SZ). The GWAS
      results implicated biologically relevant genetic loci encoding protein targets
      involved in synaptic neurotransmission, although no robust individual replication
      was detected and thus additional validation is required. Secondary permutation
      based analysis revealed an excess of strongly associated loci among GWAS top
      ranked signals for verbal working memory (WM) and antisaccade intra-subject
      reaction time variability (empirical P < 0.001), suggesting multiple true
      positive single-SNP associations. Substantial heritability was observed for WM
      performance. Further, sustained attention/vigilance and WM were suggestively
      correlated with both COGENT and PGC-SZ derived polygenic scores. Overall, these
      results imply that common genetic variation explains some of the variability in
      neurocognitive functioning among young adults, particularly WM, and provide
      supportive evidence that increased SZ genetic risk predicts neurocognitive
      fluctuations in the general population.

PMID- 25963332
TI  - The influence of Kinesiology Taping on the volume of lymphoedema and manual
      dexterity of the upper limb in women after breast cancer treatment.
AB  - The aim of our study was to evaluate the effect of Kinesiology Taping (KT) on the
      size of lymphoedema and manual dexterity of the upper limb in women after breast
      cancer treatment. We also examined whether the application of KT can replace the
      traditional and standard multilayered bandaging in the treatment of upper
      extremity lymphoedema. Group A comprised of 22 patients who underwent KT as well
      as pneumatic and manual lymphatic drainage. Then, group B comprised of 23
      patients who were treated with quasi-KT as well as pneumatic and manual lymphatic
      drainage. In contrast, group C had 25 patients subjected only to the standard
      procedure - pneumatic and manual lymphatic drainage and multilayered bandaging.
      Patient evaluation items included limb size, grip strength and range of motion.
      After 4-week therapy, we observed that KT is not an effective method of reducing
      lymphoedema II and III(0) in women after breast cancer treatment. At this moment,
      the taping cannot replace the traditional and standard multilayered bandaging in
      the treatment of upper extremity lymphoedema. 

PMID- 25963333
TI  - A subset of genetic susceptibility variants for colorectal cancer also has
      prognostic value.
AB  - We investigated the possible influence of 86 single-nucleotide polymorphisms
      (SNPs), known to associate with the risk of colorectal cancer (CRC), on overall
      survival and time to recurrence (TTR) in 733 Italian CRC patients followed up for
      up to 84 months after surgery. In the Cox multivariate analysis, adjusted for
      gender, age, pathological stage and adjuvant chemotherapy (yes/no), the risk of
      death significantly increased by rare allele count (P<0.05) for rs1801133
      (MTHFR), rs4939827 (SMAD7), rs2306283 (SLCO1B1) and rs12898159 (BMP4), whereas
      for rs736775 (GPX3) the opposite was observed. Two additional SNPs associated
      with TTR, namely rs16892766 (downstream of EIF3H) and rs10749971 (COLCA2). Our
      findings show that some genetic variants previously found to associate with CRC
      risk are also associated with survival after treatment. The identification of
      alleles defining subgroups of patients with worse clinical outcome may have
      application in developing pharmacogenetic strategies aimed at personalizing CRC
      treatment. 

PMID- 25963334
TI  - CYP2B6*6 genotype and high efavirenz plasma concentration but not nevirapine are
      associated with low lumefantrine plasma exposure and poor treatment response in
      HIV-malaria-coinfected patients.
AB  - We investigated the influence of efavirenz (EFV)- or nevirapine (NVP)-based
      antiretroviral therapy (ART) on lumefantrine plasma exposure in HIV-malaria
      coinfected patients and implication of pharmacogenetic variations. A total of 269
      HIV patients with uncomplicated falciparum malaria on NVP-based ART (NVP-arm),
      EFV-based ART (EFV-arm) or not receiving ART (control-arm) were enrolled and
      treated with artemether-lumefantrine. Day-7 lumefantrine, baseline EFV and NVP
      plasma concentrations, and CYP2B6*6,*18, CYP3A4*1B, CYP3A5*3,*6,*7, ABCB1
      c.3435C>T and ABCB1 c.4036A>G genotypes were determined. The median day-7
      lumefantrine plasma concentration was significantly lower in the EFV-arm compared
      with that in NVP- and control-arm. High EFV plasma concentrations and CYP2B6*6/*6
      genotype significantly correlated with low lumefantrine plasma concentrations and
      high rate of recurrent parasitemia. No significant effect of NVP-based ART on
      lumefantrine exposure was observed. In conclusion, owing to long-term CYP3A
      induction, EFV-based ART cotreatment significantly reduces lumefantrine plasma
      exposure leading to poor malaria treatment response, which is more pronounced in
      CYP2B6 slow metabolizers. 

PMID- 25963335
TI  - Common variants of catechol-O-methyltransferase influence patient-controlled
      analgesia usage and postoperative pain in patients undergoing total hysterectomy.
AB  - Catechol-O-methyltransferase (COMT) gene polymorphisms and haplotypes have been
      associated with both experimental and clinical pain phenotypes. In this
      prospective study, we investigated the association of three common polymorphisms
      with experimentally induced pressure pain, postoperative pain and amount of self
      administered morphine in 973 patients who underwent scheduled total hysterectomy.
      DNA extracted from peripheral blood was genotyped for three COMT polymorphisms by
      Taqman assay or a PCR-based method. In the overall sample, rs4633 and rs4680 were
      significantly associated with morphine use, whereas rs4818 was associated with
      time-averaged pain scores. Statistically significant associations were found
      between COMT rs4633 and rs4680 genotypes and the amount of morphine self
      administered through a patient-controlled analgesia pump. For rs4818, the only
      statistically significant association was with time-averaged pain scores.
      Haplotype analysis showed statistically significant association of the low pain
      sensitivity haplotype with time-averaged pain scores; and average pain
      sensitivity haplotype with total morphine and weight-adjusted morphine. 

PMID- 25963336
TI  - Genetic variation in uncontrolled childhood asthma despite ICS treatment.
AB  - Genetic variation may partly explain asthma treatment response heterogeneity. We
      aimed to identify common and rare genetic variants associated with asthma that
      was not well controlled despite inhaled corticosteroid (ICS) treatment. Data of
      110 children was collected in the Children Asthma Therapy Optimal trial.
      Associations of genetic variation with measures of lung function (FEV1%pred),
      airway hyperresponsiveness (AHR) to methacholine (Mch PD20) and treatment
      response outcomes were analyzed using the exome chip. The 17q12-21 locus
      (containing ORMDL3 and GSMDB) previously associated with childhood asthma was
      investigated separately. Single-nucleotide polymorphisms (SNPs) in the 17q12-21
      locus were found nominally associated with the outcomes. The strongest
      association in this region was found for rs72821893 in KRT25 with FEV1%pred
      (P=3.75*10(-5)), Mch PD20 (P=0.00095) and Mch PD20-based treatment outcome
      (P=0.006). No novel single SNPs or burden tests were significantly associated
      with the outcomes. The 17q12-21 region was associated with FEV1%pred and AHR, and
      additionally with ICS treatment response. 

PMID- 25963337
TI  - In vitro approach to study the synergistic effects of tobramycin and
      clarithromycin against Pseudomonas aeruginosa biofilms using prokaryotic or
      eukaryotic culture media.
AB  - Recurrent Pseudomonas aeruginosa infections involving biofilm formation are
      frequent in cystic fibrosis, aggravating the respiratory distress. Co
      administration of clarithromycin and classical tobramycin could improve the
      health status of patients. Antibiotic toxicity was assessed on epithelial
      (CFBE41o(-)) and macrophagic (THP-1) cell lines. Non-toxic concentrations of
      antibiotics alone or in combination were applied twice daily for 12 days on
      mature (12-day-old) biofilms of three P. aeruginosa strains, developed either in
      prokaryotic culture broth [tryptic soy broth (TSB)] or in a eukaryotic cell
      culture medium (RPMI-FCS) more similar to an in vivo environment. The antibiofilm
      and bactericidal effects of antibiotics were assessed. No toxicity of tobramycin
      was observed on eukaryotic cell lines at concentrations up to 500MUg/mL, whilst
      100MUg/mL was selected as the clarithromycin upper safe limit. The amount of
      biofilm was strongly reduced by 100MUg/mL and 500MUg/mL tobramycin for each
      strain in both media, whilst clarithromycin was only effective in RPMI-FBS, with
      synergistic (PAO1 strain) and additive (PYO2 strain) effects detected when
      combining tobramycin 4MUg/mL and clarithromycin 100MUg/mL. Finally, tobramycin at
      >=100MUg/mL exerted strong bactericidal effects on each strain in both media.
      Clarithromycin also exerted bactericidal effects on each strain in both media;
      its effect was weaker than tobramycin in TSB but was similar in RPMI-FBS.
      Synergistic effects were observed on PAO1 and MUCO biofilms, e.g. when combining
      tobramycin 4MUg/mL and clarithromycin 100MUg/mL. These in vitro data show that co
      administration of clarithromycin and tobramycin acts synergistically against in
      vitro P. aeruginosa biofilms. 

PMID- 25963338
TI  - Bactericidal efficacy of atmospheric pressure non-thermal plasma (APNTP) against
      the ESKAPE pathogens.
AB  - The emergence of multidrug-resistant pathogens within the clinical environment is
      presenting a mounting problem in hospitals worldwide. The 'ESKAPE' pathogens
      (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae,
      Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) have been
      highlighted as a group of causative organisms in a majority of nosocomial
      infections, presenting a serious health risk due to widespread antimicrobial
      resistance. The stagnating pipeline of new antibiotics requires alternative
      approaches to the control and treatment of nosocomial infections. Atmospheric
      pressure non-thermal plasma (APNTP) is attracting growing interest as an
      alternative infection control approach within the clinical setting. This study
      presents a comprehensive bactericidal assessment of an in-house-designed APNTP
      jet both against biofilms and planktonic bacteria of the ESKAPE pathogens.
      Standard plate counts and the XTT metabolic assay were used to evaluate the
      antibacterial effect of APNTP, with both methods demonstrating comparable
      eradication times. APNTP exhibited rapid antimicrobial activity against all of
      the ESKAPE pathogens in the planktonic mode of growth and provided efficient and
      complete eradication of ESKAPE pathogens in the biofilm mode of growth within
      360s, with the exception of A. baumannii where a >4log reduction in biofilm
      viability was observed. This demonstrates its effectiveness as a bactericidal
      treatment against these pathogens and further highlights its potential
      application in the clinical environment for the control of highly antimicrobial
      resistant pathogens. 

PMID- 25963339
TI  - In vitro evaluation of the antibiofilm properties of chlorhexidine and delmopinol
      on dental implant surfaces.
AB  - Biofilm development on the internal surfaces of dental implants and dental
      implant components may be associated with peri-implant hard and soft tissue
      abnormalities. Currently, no protocols have been established for effective
      disinfection of removable implant components. The purpose of this study was to
      evaluate the antibiofilm properties of commonly used dental antimicrobial agents
      (chlorhexidine and delmopinol) on multispecies biofilms. Biofilms of 48 h and 168
      h maturity were exposed to 0.2% chlorhexidine, 2% chlorhexidine and a product
      containing 0.2% delmopinol for 5, 10 and 20 min. 2% chlorhexidine was the most
      effective agent, achieving a total viable biofilm reduction ranging from 96.2% to
      >99.99% depending on the time of exposure and the stage of biofilm development.

PMID- 25963340
TI  - Knockdown of different influenza A virus subtypes in cell culture by a single
      antisense oligodeoxyribonucleotide.
AB  - Influenza is a heavy socially significant viral infection that affects humans,
      birds, and wild and domestic animals. The threat of existing and new highly
      pathogenic subtypes of influenza A virus (IAV) makes it necessary to develop an
      effective drug that may affect different IAV strains. For this purpose,
      oligodeoxynucleotides (DNA fragments) attached to titanium dioxide (TiO2)
      nanoparticles through a polylysine linker, forming TiO2.PL-DNA nanocomposites,
      that penetrated into cells without transfection agents were used. For the first
      time, efficient (>=99.9%) suppression of the reproduction of different subtypes
      of IAV, including highly pathogenic H5N1 and H1N1, was achieved. These results
      were obtained using the TiO2.PL-DNA nanocomposite bearing a single antisense
      oligodeoxynucleotide (0.1MUM) targeted to the conserved 3'-noncoding region of
      RNA segment 5, which is common to all tested strains. Very efficient suppression
      of the reproduction of different subtypes of IAV was probably achieved due to the
      use of the proposed delivery system for oligonucleotides in the form of the
      TiO2.PL-DNA nanocomposites. These results indicate the possibility of creating an
      efficient drug to affect existing and newly emerging pathogenic IAV strains. 

PMID- 25963341
TI  - Erratum to: Genetic Adaptation of Influenza A Viruses in Domestic Animals and
      Their Potential Role in Interspecies Transmission: A Literature Review.

PMID- 25963342
TI  - Single Causative Factor for Severe Pneumonia Epizootics in Muskoxen?

PMID- 25963343
TI  - A meta-analysis of surgical success rates in congenital stapes fixation and
      juvenile otosclerosis.
AB  - OBJECTIVES: To assess published reports in the literature on surgical success
      rates in patients with congenital stapes fixation (CSF) and juvenile otosclerosis
      (JO). DESIGN: Systematic review of the literature and meta-analysis of published
      data. DATA SOURCES: PubMed, SAGE, MEDLINE, and Cochrane. REVIEW METHODS: A
      literature search was performed and evaluated based on established criteria. Two
      independent reviewers (b.a., m.b.) inspected titles and abstracts of the studies.
      The full texts of the studies were examined to assess their relevance to the meta
      analysis. An air-bone gap (ABG) of 0 to 10 dB hearing level was described as
      success of surgery. RESULTS: A random effects model was used to analyze the data.
      A total of 27 studies were included in the meta-analysis, whereas 934 were
      excluded. The total number of operated ears was 445 (256 ears with JO and 189
      ears with CSF). At the time of surgery, the age of the patients ranged from 3 to
      18 years. The success rate was 80.2% for JO and 54% for CSF. The overall success
      rate was 69.9%. The rate of postoperative sensorineural hearing loss was 3.4% for
      JO and 2.1% for CSF. CONCLUSIONS: Overall, stapes surgery in children with JO or
      CSF has a moderate success rate (69.9%) to provide ABG closure of 10 dB. The
      success rate for CSF in the setting of ossicular abnormalities is 54%. This meta
      analysis suggests that if JO can be determined before surgery, a higher success
      rate is possible (80.2%).

PMID- 25963344
TI  - Effect of transcatheter arterial embolization with a mixture of n-butyl
      cyanoacrylate, lipiodol, and ethanol on the vascular wall: macroscopic and
      microscopic studies.
AB  - PURPOSE: To compare the pathologic effect of a mixture of n-butyl cyanoacrylate
      (NBCA), lipiodol, and ethanol (NLE) with a mixture of NBCA and lipiodol (NL) on
      the embolized vascular wall. MATERIALS AND METHODS: Embolization was performed
      using four swine with NBCA and lipiodol in a volume ratio of 1:1 (NL11 group) in
      the common hepatic artery (n = 1) and the internal iliac artery (n = 2); and with
      NBCA, lipiodol, and ethanol in a volume ratio of 1:1:2 (NLE112 group) in the
      common hepatic artery (n = 3) and the internal iliac artery (n = 6). RESULTS:
      NL11 casts had an intricate appearance in reticular configuration with red
      thrombus, while NLE112 casts presented in a single round configuration with
      surrounding ring-like red thrombus. Desquamation of endothelial cells and
      infiltration of neutrophils into the adventitial layer were found in all
      embolized vessels in both groups. Infiltration of neutrophils into the
      intermediate layer was found in the NL11 group but not in the NLE112 group.
      CONCLUSION: The damage to the vascular wall caused by NLE112 was milder than that
      by NL11, implying the adverse effects of NLE112 are within tolerable limits.

PMID- 25963345
TI  - Efficacy and safety of avandamet or uptitrated metformin treatment in patients
      with type 2 diabetes inadequately controlled with metformin alone: a multicenter,
      randomized, controlled trial.
AB  - BACKGROUND: At present, China has listed the compound tablet containing a fixed
      dose of rosiglitazone and metformin, Avandamet, which may improve patient
      compliance. The aim of this study was to evaluate the efficacy and safety of
      Avandamet or uptitrated metformin treatment in patients with type 2 diabetes
      inadequately controlled with metformin alone. METHODS: This study was a 48-week,
      multicenter, randomized, open-labeled, active-controlled trial. Patients with
      inadequate glycaemic control (glycated hemoglobin [HbA1c] 7.5-9.5%) receiving a
      stable dose of metformin (>=1500 mg) were recruited from 21 centers in China
      (from 19 November, 2009 to 15 March, 2011). The primary objective was to compare
      the proportion of patients who reached the target of HbA1c <=7% between Avandamet
      and metformin treatment. RESULTS: At week 48, 83.33% of patients reached the
      target of HbA1c <=7% in Avandamet treatment and 70.00% in uptitrated metformin
      treatment, with significantly difference between groups. The target of HbA1c
      <=6.5% was reached in 66.03% of patients in Avandamet treatment and 46.88% in
      uptitrated metformin treatment. The target of fasting plasma glucose (FPG) <=6.1
      mmol/L was reached in 26.97% of patients in Avandamet treatment and 19.33% in
      uptitrated metformin treatment. The target of FPG <=7.0 mmol/L was reached in
      63.16% of patients in Avandamet treatment and 43.33% in uptitrated metformin
      treatment. Fasting insulin decreased 3.24 +/- 0.98 MUU/ml from baseline in
      Avandamet treatment and 0.72 +/- 1.10 MUU/ml in uptitrated metformin treatment.
      Overall adverse event (AE) rates and serious AE rates were similar between
      groups. Hypoglycaemia occurred rarely in both groups. CONCLUSIONS: Compared with
      uptitrated metformin, Avandamet treatment provided significant improvements in
      key parameters of glycemic control and was generally well tolerated. REGISTRATION
      NUMBER: ChiCTR-TRC-13003776.

PMID- 25963346
TI  - Impact of libido at 2 weeks after stroke on risk of stroke recurrence at 1-year
      in a chinese stroke cohort study.
AB  - BACKGROUND: There were few studies on the relation between changes in libido and
      incidence of stroke recurrence. The aim of this study was to investigate the
      relationship between libido decrease at 2 weeks after stroke and recurrent stroke
      at 1-year. METHODS: It is a multi-centered, prospective cohort study. The 14 th
      item of the Hamilton Depression Rating Scale-17 was used to evaluate changes of
      libido in poststroke patients at 2 weeks. Stroke recurrence was defined as an
      aggravation of former neurological functional deficit, new local or overall
      symptoms, or stroke diagnosed at re-admission. RESULTS: Among 2341 enrolled
      patients, 1757 patients had completed follow-up data, 533 (30.34%) patients had
      decreased libido at 2 weeks, and 166 (9.45%) patients had recurrent stroke at 1
      year. Multivariate logistic regression analysis showed that, compared with
      patients with normal libido, the odds ratio (OR) of recurrent stroke in patients
      with decreased libido was reduced by 41% (OR = 0.59, 95% confidence interval
      [CI]: 0.40-0.87). The correlation was more prominent among male patients (OR =
      0.52, 95% CI: 0.31-0.85) and patients of >=60 years of age (OR = 0.57, 95% CI:
      0.35-0.93). CONCLUSIONS: One out of three stroke patients in mainland China has
      decreased libido at 2 weeks after stroke. Decreased libido is a protective factor
      for stroke recurrence at 1-year, which is more prominent among older male
      patients.

PMID- 25963347
TI  - Awareness Status of Chronic Disabling Neurological Diseases among Elderly
      Veterans.
AB  - BACKGROUND: The awareness, treatment and prevention of chronic diseases are
      generally poor among the elderly population of China, whereas the prevention and
      control of chronic diseases in elderly veteran communities have been ongoing for
      more than 30 years. Therefore, investigating the awareness status of chronic
      disabling neurological diseases (CDND) and common chronic diseases (CCD) among
      elderly veterans may provide references for related programs among the elderly in
      the general population. METHODS: A cross-sectional survey was conducted among
      veterans >=60 years old in veteran communities in Beijing. The awareness of
      preventive strategies against dementia, Alzheimer's disease (AD), Parkinson's
      disease (PD), sleep disorders, cerebrovascular disease (CVD) and CCD such as
      hypertension, and the approaches used to access this information, including
      media, word of mouth (verbal communication among the elderly) and health care
      professionals, were investigated via face-to-face interviews. RESULTS: The
      awareness rates for CCD and CVD were approximately 100%, but that for AD was the
      lowest at <10%. The awareness rates for sleep disorders, PD and dementia, were
      51.0-89.4%. Media was the most commonly selected mode of communication by which
      veterans acquired knowledge about CCD and CVD. Media was used by approximately
      80% of veterans. Both health care professionals and word of mouth were used by
      approximately 50% of veterans. With respect to the source of information about
      CDND excluding AD, the rates of the use of health care professionals, word of
      mouth and media were 10.6-28.2%, 56.5-76.5%, and approximately 50%, respectively.
      CONCLUSIONS: The awareness of CDND among elderly veterans was significantly lower
      than that of CCD. More information about CDND should be disseminated by health
      care professionals. Appropriate guidance will promote the rapid and extensive
      dissemination of information about the prevention of CDND by media and word-of
      mouth peer education.

PMID- 25963348
TI  - Evaluation of the effects of standard rescue procedure on severe trauma treatment
      in china.
AB  - BACKGROUND: This study aimed to evaluate the effects of standard rescue procedure
      (SRP) in improving severe trauma treatments in China. METHODS: This study was
      conducted in 12 hospitals located in geographically and industrially different
      cities in China. A standard procedure on severe trauma rescue was established as
      a general rule for staff training and patient treatment. A regional network
      (system) efficiently integrating prehospital rescue, emergency room treatments,
      and hospital specialist treatments was built under the rule for information
      sharing and improving severe trauma treatments. Treatment outcomes were compared
      between before and 1 year after the implementation of the SRP. RESULTS: The
      outcomes of a total of 74,615 and 12,051 trauma cases were collected from 12
      hospitals before and after the implementation of the SRP. Implementation of the
      SRP led to efficient cooperation and information sharing of different treatment
      services. The emergency response time, prehospital transit time, emergency rescue
      time, consultation call time, and mortality rate of patients were 24.24 +/- 4.32
      min, 45.69 +/- 3.89 min, 6.38 +/- 1.05 min, 17.53 +/- 0.72 min, and 33.82% +/-
      3.87% (n = 441), respectively, before the implementation of the standardization
      and significantly reduced to 10.11 +/- 3.21 min, 22.39 +/- 4.32 min, 3.26 +/-
      0.89 min, 3.45 +/- 0.45 min, and 20.49% +/- 3.11%, separately (n = 495, P < 0.05)
      after that. CONCLUSIONS: Staff training and SRP can significantly improve the
      efficiency of severe trauma treatments in China.

PMID- 25963349
TI  - The Use of the Ratio between the Veno-arterial Carbon Dioxide Difference and the
      Arterial-venous Oxygen Difference to Guide Resuscitation in Cardiac Surgery
      Patients with Hyperlactatemia and Normal Central Venous Oxygen Saturation.
AB  - BACKGROUND: After cardiac surgery, central venous oxygen saturation (ScvO 2 ) and
      serum lactate concentration are often used to guide resuscitation; however,
      neither are completely reliable indicators of global tissue hypoxia. This
      observational study aimed to establish whether the ratio between the veno
      arterial carbon dioxide and the arterial-venous oxygen differences (P(v-a)CO 2
      /C(a-v)O 2 ) could predict whether patients would respond to resuscitation by
      increasing oxygen delivery (DO 2 ). METHODS: We selected 72 patients from a
      cohort of 290 who had undergone cardiac surgery in our institution between
      January 2012 and August 2014. The selected patients were managed postoperatively
      on the Intensive Care Unit, had a normal ScvO 2 , elevated serum lactate
      concentration, and responded to resuscitation by increasing DO 2 by >10%. As a
      consequence, 48 patients responded with an increase in oxygen consumption (VO 2 )
      while VO 2 was static or fell in 24. RESULTS: At baseline and before
      resuscitative intervention in postoperative cardiac surgery patients, a P(v-a)CO
      2 /C(a-v)O 2 ratio >=1.6 mmHg/ml predicted a positive VO 2 response to an
      increase in DO 2 of >10% with a sensitivity of 68.8% and a specificity of 87.5%.
      CONCLUSIONS: P(v-a)CO 2 /C(a-v)O 2 ratio appears to be a reliable marker of
      global anaerobic metabolism and predicts response to DO 2 challenge. Thus,
      patients likely to benefit from resuscitation can be identified promptly, the P(v
      a)CO 2 /C(a-v)O 2 ratio may, therefore, be a useful resuscitation target.

PMID- 25963350
TI  - Efficacy and safety of domestic leuprorelin in girls with idiopathic central
      precocious puberty: a multicenter, randomized, parallel, controlled trial.
AB  - BACKGROUND: In central precocious puberty (CPP), the pulse secretion and release
      of gonadotropin-releasing hormone (GnRH) are increased due to early activation of
      the hypothalamic-pituitary-gonadal axis, resulting in developmental abnormalities
      with gonadal development and appearance of secondary sexual characteristics. The
      CPP without organic disease is known as idiopathic CPP (ICPP). The objective of
      the study was to evaluate the clinical efficacy and safety of domestic
      leuprorelin (GnRH analog) in girls with ICPP. METHODS: A total of 236 girls with
      ICPP diagnosed from April 2012 to January 2014 were selected and were randomized
      into two groups. One hundred fifty-seven girls in the test group were treated
      with domestic leuprorelin acetate, 79 girls in the control group were treated
      with imported leuprorelin acetate. They all were treated and observed for 6
      months. After 6-month treatment, the percentage of children with peak luteinizing
      hormone (LH) <=3.3 U/L, the percentage of children with peak LH/peak follicle
      stimulating hormone (FSH) ratio <0.6, the improvements of secondary sexual
      characteristics, gonadal development and sex hormone levels, the change of growth
      rate of bone age (BA) and growth velocity, and drug adverse effects between two
      groups were compared. RESULTS: After the treatment, the percentage of children
      with a suppressed LH response to GnRH, defined as a peak LH <=3.3 U/L, at 6
      months in test and control groups were 96.80% and 96.20%, respectively, and the
      percentage of children with peak LH/FSH ratio <=0.6 at 6 months in test and
      control groups were 93.60% and 93.70%, respectively. The sizes of breast, uterus
      and ovary of children and the levels of estradiol (E 2 ) were significantly
      reduced, and the growth rate of BA was also reduced. All the differences between
      pre- and post-treatment in each group were statistically significant (P < 0. 05),
      but the differences of the parameters between two groups were not significant (P
      > 0.05). CONCLUSIONS: Domestic leuprorelin is effective and safe in the treatment
      of Chinese girls with ICPP. Its effectiveness and safety are comparable with
      imported leuprorelin.

PMID- 25963351
TI  - Effects of Moderate Hyperventilation on Jugular Bulb Gases under Propofol or
      Isoflurane Anesthesia during Supratentorial Craniotomy.
AB  - BACKGROUND: The optimal ventilated status under total intravenous or inhalation
      anesthesia in neurosurgical patients with a supratentorial tumor has not been
      ascertained. The purpose of this study was to intraoperatively compare the
      effects of moderate hyperventilation on the jugular bulb oxygen saturation (SjO 2
      ), cerebral oxygen extraction ratio (O 2 ER), mean arterial blood pressure (MAP),
      and heart rate (HR) in patients with a supratentorial tumor under different
      anesthetic regimens. METHODS: Twenty adult patients suffered from supratentorial
      tumors were randomly assigned to receive a propofol infusion followed by
      isoflurane anesthesia after a 30-min stabilization period or isoflurane followed
      by propofol. The patients were randomized to one of the following two treatment
      sequences: hyperventilation followed by normoventilation or normoventilation
      followed by hyperventilation during isoflurane or propofol anesthesia,
      respectively. The ventilation and end-tidal CO 2 tension were maintained at a
      constant level for 20 min. Radial arterial and jugular bulb catheters were
      inserted for the blood gas sampling. At the end of each study period, we measured
      the change in the arterial and jugular bulb blood gases. RESULTS: The mean value
      of the jugular bulb oxygen saturation (SjO 2 ) significantly decreased, and the
      oxygen extraction ratio (O 2 ER) significantly increased under isoflurane or
      propofol anesthesia during hyperventilation compared with those during
      normoventilation (SjO 2 : t = -2.728, P = 0.011 or t = -3.504, P = 0.001; O 2 ER:
      t = 2.484, P = 0.020 or t = 2.892, P = 0.009). The SjO 2 significantly decreased,
      and the O 2 ER significantly increased under propofol anesthesia compared with
      those values under isoflurane anesthesia during moderate hyperventilation (SjO 2
      : t = -2.769, P = 0.012; O 2 ER: t = 2.719, P = 0.013). In the study, no
      significant changes in the SjO 2 and the O 2 ER were observed under propofol
      compared with those values under isoflurane during normoventilation. CONCLUSIONS:
      Our results suggest that the optimal ventilated status under propofol or
      isoflurane anesthesia in neurosurgical patients varies. Hyperventilation under
      propofol anesthesia should be cautiously performed in neurosurgery to maintain an
      improved balance between the cerebral oxygen supply and demand.

PMID- 25963352
TI  - Management of Benign Tracheal Stenosis by Small-diameter Tube-assisted
      Bronchoscopic Balloon Dilatation.
AB  - BACKGROUND: A limitation of bronchoscopic balloon dilatation (BBD) is that
      airflow must be completely blocked for as long as possible during the operation.
      However, the patient often cannot hold his or her breath for a long period
      affecting the efficacy of the procedure. In this study, we used an extra-small
      diameter tube to provide assisted ventilation to patients undergoing BBD and
      assessed the efficacy and safety of this technique. METHODS: Bronchoscopic
      balloon dilatation was performed in 26 patients with benign tracheal stenosis
      using an extra-small-diameter tube. The tracheal diameter, dyspnea index, blood
      gas analysis results, and complications were evaluated before and after BBD.
      Statistical analyses were performed by SPSS version 16.0 for Windows (SPSS, Inc.,
      Chicago, IL, USA). RESULTS: Sixty-three BBD procedures were performed in 26
      patients. Dyspnea immediately improved in all patients after BBD. The tracheal
      diameter significantly increased from 5.5 +/- 1.5 mm to 13.0 +/- 1.3 mm (P <
      0.001), and the dyspnea index significantly decreased from 3.4 +/- 0.8 to 0.5 +/-
      0.6 (P < 0.001). There was no significant change in the partial pressure of
      oxygen during the operation (before, 102.5 +/- 27.5 mmHg; during, 96.9 +/- 30.4
      mmHg; and after, 97.2 +/- 21.5 mmHg; P = 0.364), but there was slight temporary
      retention of carbon dioxide during the operation (before, 43.5 +/- 4.2 mmHg;
      during, 49.4 +/- 6.8 mmHg; and after, 40.1 +/- 3.9 mmHg; P < 0.001). CONCLUSION:
      Small-diameter tube-assisted BBD is an effective and safe method for the
      management of benign tracheal stenosis.

PMID- 25963353
TI  - Mortality trend and predictors of mortality in dysphagic stroke patients
      postpercutaneous endoscopic gastrostomy.
AB  - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) feeding is widely used in
      stroke patients suffering from persistent dysphagia; however, predicting the
      risks and benefits of PEG insertion in the individual patient is difficult. The
      aim of our study was to investigate if candidate risk factors could predict short
      term mortality risk in poststroke patients who had PEG tube insertion for
      persistent dysphagia. METHODS: This was a retrospective study of 3504 consecutive
      stroke patients admitted to two metropolitan hospitals during the period January
      2005 to December 2013 and who also underwent PEG insertion for feeding due to
      persistent dysphagia. RESULTS: A total of 102 patients were included in the
      study. There were 22 deaths in 6 months after insertion of PEG tubes and 20
      deaths of those occurred within 3 months post PEG. Those who survived beyond 6
      months showed significantly lower mean age (75.9 +/- 9.0 years vs. 83.0 +/- 4.9
      years, P < 0.001), a lower mean American Society of Anesthesia (ASA) score (3.04
      +/- 0.63 vs. 3.64 +/- 0.58, P < 0.001) compared to nonsurvivors. In multiple
      Logistic, age (P = 0.004, odds ratio [OR] = 1.144; 95% confidence interval [CI]:
      1.044-1.255); ASA (P = 0.002, OR = 5.065; 95% CI: 1.815-14.133) and albumin level
      pre-PEG insertion (P = 0.033, OR = 0.869; 95% CI: 0.764-0.988) were the
      independent determinants of mortality respectively. CONCLUSIONS: We propose that
      age, ASA score and albumin level pre-PEG insertion to be included as factors to
      assist in the selection of patients who are likely to survive more than 3 months
      post PEG insertion.

PMID- 25963354
TI  - Identification of a novel mutation in solute carrier family 29, member 3 in a
      Chinese patient with H syndrome.
AB  - BACKGROUND: H syndrome (OMIM 612391) is a recently described autosomal recessive
      genodermatosis characterized by indurated hyperpigmented and hypertrichotic skin,
      as well as other systemic manifestations. Most of the cases occurred in the
      Middle East areas or nearby countries such as Spain or India. The syndrome is
      caused by mutations in solute carrier family 29, member 3 (SLC29A3), the gene
      encoding equilibrative nucleoside transporter 3. The aim of this study was to
      identify pathogenic SLC29A3 mutations in a Chinese patient clinically diagnosed
      with H syndrome. METHODS: Peripheral blood samples were collected from the
      patient and his parents. Genomic DNA was isolated by the standard method. All six
      SLC29A3 exons and their flanking intronic sequences were polymerase chain
      reaction (PCR)-amplified and the PCR products were subjected to direct
      sequencing. RESULTS: The patient, an 18-year-old man born to a nonconsanguineous
      Chinese couple, had more extensive cutaneous lesions, involving both buttocks and
      knee. In his genomic DNA, we identified a novel homozygous insertion-deletion, c.
      1269_1270delinsA, in SLC29A3. Both of his parents were carriers of the mutation.
      CONCLUSIONS: We have identified a pathogenic mutation in a Chinese patient with H
      syndrome.

PMID- 25963355
TI  - Application of laparoscopic extralevator abdominoperineal excision in locally
      advanced low rectal cancer.
AB  - BACKGROUND: When compared with conventional abdominoperineal resection (APR),
      extralevator abdominoperineal excision (ELAPE) has been demonstrated to reduce
      the risk of local recurrence for the treatment of locally advanced low rectal
      cancer. Combined with the laparoscopic technique, laparoscopic ELAPE (LELAPE) has
      the potential to reduce invasion and hasten postoperative recovery. In this
      study, we aim to investigate the advantages of LELAPE in comparison with
      conventional APR. METHODS: From October 2010 to February 2013, 23 patients with
      low rectal cancer (T 3-4 N 0-2 M 0 ) underwent LELAPE; while during the same
      period, 25 patients were treated with conventional APR. The patient
      characteristics, intraoperative data, postoperative complications, and follow-up
      results were retrospectively compared and analyzed. RESULTS: The basic patient
      characteristics were similar; but the total operative time for the LELAPE was
      longer than that of the conventional APR group (P = 0.014). However, the
      operative time for the perineal portion was comparable between the two groups (P
      = 0.328). The LELAPE group had less intraoperative blood loss (P = 0.022), a
      lower bowel perforation rate (P = 0.023), and a positive circumferential margin
      (P = 0.028). Moreover, the patients, who received the LELAPE, had a lower
      postoperative Visual Analog Scale, quicker recovery of bowel function (P =
      0.001), and a shorter hospital stay (P = 0.047). However, patients in the LELAPE
      group suffered more chronic perineal pain (P = 0.002), which may be related to
      the coccygectomy (P = 0.033). Although the metastasis rate and mortality rate
      were similar between the two groups, the local recurrence rate of the LELAPE
      group was statistically improved (P = 0.047). CONCLUSIONS: When compared with
      conventional APR, LELAPE has the potential to reduce the risk of local
      recurrence, and decreases operative invasion for the treatment of locally
      advanced low rectal cancer.

PMID- 25963356
TI  - Changes in Intra-pelvic Obliquity Angle 0-2 Years After Total Hip Arthroplasty
      and Its Effects on Leg Length Discrepancy: A Retrospective Study.
AB  - BACKGROUND: Total hip arthroplasty (THA) is one of the most effective treatments
      for phase III and IV hip arthrosis. Lower limb length balancing is one of the
      determining factors of a successful surgery, particularly in patients with
      developmental dysplasia of the hip (DDH). The purpose of this study was to
      evaluate the postoperative change in intra-pelvic obliquity (intra-PO) angle in
      the coronal plane and its effects on leg length discrepancy (LLD) within 2 years.
      METHODS: A total of 78 patients (70 females, 8 males) were enrolled in this
      study. All patients were suffering from DDH with varying degrees of LLD. Pelvic
      plain radiographs were collected before and after the operation. The intra-PO
      angles were measured 0, 0.5, 1 and 2 years after THA. At the same time,
      postoperative LLD was measured with blocking test. RESULTS: PO changed
      significantly in the first year after THA surgery (0 year vs. 0.5 year, P < 0.01;
      0.5 year vs. 1 year, P < 0.01), and the changing value of intra-PO angle
      (DeltaPO) slowed down substantially during the first 2 years after THA (0.5 year
      vs. 0.5-1 year, P < 0.01; 0.5-1 year vs. 1-2 years, P < 0.01). With the change in
      intra-PO angle, LLD also got narrow within the 1st year (0 year vs. 0.5 year, P <
      0.01; 0.5 year vs. 1 year, P < 0.01). Elderly patients had a smaller intra-PO
      angle reduction (Group A vs. Group B, P = 0.01; Group B vs. Group C, P < 0.01).
      CONCLUSIONS: Intra-PO angle and LLD gap narrowed with time after THA surgery. In
      particular, elderly patients had smaller change in intra-PO angle.

PMID- 25963357
TI  - Serum hepcidin predicts uremic accelerated atherosclerosis in chronic
      hemodialysis patients with diabetic nephropathy.
AB  - BACKGROUND: Hepcidin, as a regulator of body iron stores, has been recently
      discovered to play a critical role in the pathogenesis of anemia of chronic
      disease. Atherosclerotic cardiovascular disease is the most common complication
      and the leading cause of death in chronic hemodialysis (CHD) patients. In the
      current study, we aimed to explore the relationship between serum hepcidin and
      uremic accelerated atherosclerosis (UAAS) in CHD patients with diabetic
      nephropathy (CHD/DN). METHODS: A total of 78 CHD/DN and 86 chronic hemodialyzed
      nondiabetic patients with chronic glomerulonephritis (CHD/non-DN) were recruited
      in this study. The level of serum hepcidin-25 was specifically measured by liquid
      chromatography-tandem mass spectrometry. Serum levels of interleukin-6 (IL-6) and
      tumor necrosis factor-alpha (TNF-alpha) were measured by enzyme-linked
      immunosorbent assay. RESULTS: High serum level of hepcidin-25 was seen in CHD
      patients. Serum hepcidin-25 in CHD/DN was significantly higher than that in
      CHD/non-DN patients. Serum hepcidin-25 was positively correlated with ferritin,
      high-sensitivity C-reactive protein (hs-CRP), TNF-alpha, and IL-6 in CHD/DN
      patients. CHD/DN patients exhibited higher common carotid artery intima media
      thickness (CCA-IMT), hs-CRP, and hepcidin-25 levels than that in CHD/non-DN
      patients. Moreover, in CHD/DN patients, CCA-IMT was positively correlated with
      serum hepcidin, hs-CRP, and low-density lipoprotein-cholesterol. On multiple
      regression analysis, serum hepcidin and hs-CRP level exhibited independent
      association with IMT in CHD/DN patients. CONCLUSIONS: These findings suggest
      possible linkage between iron metabolism and hepcidin modulation abnormalities
      that may contribute to the development of UAAS in CHD/DN patients.

PMID- 25963358
TI  - Analysis of Risk Factors for Lower-limb Deep Venous Thrombosis in Old Patients
      after Knee Arthroplasty.
AB  - BACKGROUND: Deep venous thrombosis (DVT) is a common complication of arthroplasty
      in old patients. We analyzed risk factors for lower-limb DVT after arthroplasty
      in patients aged over 70 years to determine controllable risk factors. METHODS:
      This was a retrospective study of 1,025 patients aged >70 years treated with knee
      arthroplasty at our hospital between January 2009 and December 2013. Of 1,025
      patients, 175 had postoperative lower-limb DVT. We compared medical history, body
      mass index (BMI), ambulatory blood pressure, preoperative and postoperative
      fasting blood glucose (FBG), preoperative blood total cholesterol, triglyceride,
      high- and low-density lipoprotein cholesterol, and preoperative homocysteine
      (Hcy) between thrombus and non-thrombus groups. B-mode ultrasonography was used
      to detect lower-limb DVT before the operation and 7 days after the operation in
      all patients. Logistic regression analysis was used to determine risk factors for
      DVT. RESULTS: Incidence of diabetes (P = 0.014), BMI (P = 0.003), preoperative
      FBG (P = 0.004), postoperative FBG (P = 0.012), and preoperative Hcy (P < 0.001)
      were significantly higher in the thrombus group. A significantly greater
      proportion of patients in the non-thrombus group had early postoperative activity
      (P < 0.001) and used a foot pump (P < 0.001). Operative duration was
      significantly longer in the thrombus group (P = 0.012). Within the thrombus
      group, significantly more patients had bilateral than unilateral knee
      arthroplasty (P < 0.01). Multivariate logistic analysis revealed BMI,
      preoperative Hcy, postoperative FBG, long operative duration, bilateral knee
      arthroplasty, and time to the activity after the operation to be predictive
      factors of DVT. At 6-month follow-up of the thrombus group, 4.7% of patients had
      pulmonary embolism and 18.8% had recurrent DVT; there were no deaths.
      CONCLUSIONS: Obesity, inactivity after operation, elevated preoperative Hcy and
      postoperative FBG, long operative duration, and bilateral knee arthroplasty were
      risk factors for DVT in patients aged over 70 years.

PMID- 25963359
TI  - Auditory Rehabilitation in Rhesus Macaque Monkeys (Macaca mulatta) with Auditory
      Brainstem Implants.
AB  - BACKGROUND: The auditory brainstem implants (ABIs) have been used to treat
      deafness for patients with neurofibromatosis Type 2 and nontumor patients. The
      lack of an appropriate animal model has limited the study of improving hearing
      rehabilitation by the device. This study aimed to establish an animal model of
      ABI in adult rhesus macaque monkey (Macaca mulatta). METHODS: Six adult rhesus
      macaque monkeys (M. mulatta) were included. Under general anesthesia, a
      multichannel ABI was implanted into the lateral recess of the fourth ventricle
      through the modified suboccipital-retrosigmoid (RS) approach. The electrical
      auditory brainstem response (EABR) waves were tested to ensure the optimal
      implant site. After the operation, the EABR and computed tomography (CT) were
      used to test and verify the effectiveness via electrophysiology and anatomy,
      respectively. The subjects underwent behavioral observation for 6 months, and the
      postoperative EABR was tested every two weeks from the 1 st month after implant
      surgery. RESULT: The implant surgery lasted an average of 5.2 h, and no monkey
      died or sacrificed. The averaged latencies of peaks I, II and IV were 1.27, 2.34
      and 3.98 ms, respectively in the ABR. One-peak EABR wave was elicited in the
      operation, and one- or two-peak waves were elicited during the postoperative
      period. The EABR wave latencies appeared to be constant under different stimulus
      intensities; however, the amplitudes increased as the stimulus increased within a
      certain scope. CONCLUSIONS: It is feasible and safe to implant ABIs in rhesus
      macaque monkeys (M. mulatta) through a modified suboccipital RS approach, and
      EABR and CT are valid tools for animal model establishment. In addition, this
      model should be an appropriate animal model for the electrophysiological and
      behavioral study of rhesus macaque monkey with ABI.

PMID- 25963360
TI  - Macroscopic and histological evaluations of meniscal allograft transplantation
      using gamma irradiated meniscus: a comparative in vivo animal study.
AB  - BACKGROUND: Many studies suggest that the gamma irradiation decreases allograft
      strength in a dose-dependent manner. However, no study has demonstrated that this
      decrease in strength translates into higher failure rate in meniscal allograft
      transplantation (MAT). The aim of this study was to investigate the effects of
      gamma irradiation on macroscopic and histological alterations of transplanted
      meniscal tissue and joint cartilage after MAT. METHODS: Medial total
      meniscectomies were performed on the right knees of 60 New Zealand white rabbits.
      All meniscal allografts were divided into three groups (20 in each group) and
      then sterilized with 0 Mrad, 1.5 Mrad, or 2.5 Mrad of gamma irradiation. For each
      group, 5 menisci were randomly chosen for scanning electron microscopic (SEM)
      analysis and the remaining 15 were prepared for MAT surgeries. Forty-five right
      knees received MAT surgeries (0 Mrad group, 1.5 Mrad group, 2.5 Mrad group, 15 in
      each group), whereas the remaining 15 only received medial meniscectomy (Meni
      group). The left knees of the Meni group were chosen as the Sham group (n = 15).
      All the rabbits were sacrificed at week 24 postoperatively. Cartilage of the
      medial compartment of each group was evaluated macroscopically using the
      International Cartilage Repair Society (ICRS) score and then histologically using
      the Mankin score based on the Masson Trichrome staining. RESULTS: The SEM
      analysis confirmed that the meniscal collagen fibers would be significantly
      damaged as the dose of gamma irradiation increased. At week 24, the overall
      scores of macroscopic evaluations of the transplanted meniscal tissue showed no
      significant differences among the three groups receiving MAT surgeries, except
      for 2 in the 2.5 Mrad group presented partial radial tears at midbody. The ICRS
      scores and the Mankin scores showed the lowest in the Sham group and the highest
      in the Meni group (P < 0.05). For the three groups receiving MAT surgeries, the
      2.5 Mrad group showed significant higher ICRS scores and Mankin scores than both
      the 0 Mrad group and the 1.5 Mrad group (P < 0.05). Whereas the 1.5 Mrad group
      presented similar results to the 0 Mrad group concerning both the ICRS scores and
      the Mankin scores. CONCLUSIONS: The current in vivo animal study proved that
      although the meniscal collagen fibers were damaged after gamma irradiation, the
      failure rate of MAT surgeries might not significantly increase if the irradiation
      dose was <1.5 Mrad for New Zealand white rabbits.

PMID- 25963361
TI  - Role of Wnt Inhibitory Factor-1 in Inhibition of Bisdemethoxycurcumin Mediated
      Epithelial-to-Mesenchymal Transition in Highly Metastatic Lung Cancer 95D Cells.
AB  - BACKGROUND: Bisdemethoxycurcumin (BDMC) is an active component of curcumin and a
      chemotherapeutic agent, which has been suggested to inhibit tumor growth,
      invasion and metastasis in multiple cancers. But its contribution and mechanism
      of action in invasion and metastasis of non-small cell lung cancer (NSCLC) are
      not very clear. Therefore, we tried to study the effects of BDMC on regulation of
      epithelial-to-mesenchymal transition (EMT), which is closely linked to tumor cell
      invasion and metastasis. METHODS: In this study, we first induced transforming
      growth factor-beta1 (TGF-beta1) mediated EMT in highly metastatic lung cancer 95D
      cells. Thereafter, we studied the effects of BDMC on invasion and migration of
      95D cells. In addition, EMT markers expressions were also analyzed by western
      blot and immunofluorescence assays. The contribution of Wnt inhibitory factor-1
      (WIF-1) in regulating BDMC effects on TGF-beta1 induced EMT were further analyzed
      by its overexpression and small interfering RNA knockdown studies. RESULTS: It
      was observed that BDMC inhibited the TGF-beta1 induced EMT in 95D cells.
      Furthermore, it also inhibited the Wnt signaling pathway by upregulating WIF-1
      protein expression. In addition, WIF-1 manipulation studies further revealed that
      WIF-1 is a central molecule mediating BDMC response towards TGF-beta1 induced EMT
      by regulating cell invasion and migration. CONCLUSIONS: Our study concluded that
      BDMC effects on TGF-beta1 induced EMT in NSCLC are mediated through WIF-1 and
      elucidated a novel mechanism of EMT regulation by BDMC.

PMID- 25963362
TI  - Human Sulfatase-1 Improves the Effectiveness of Cytosine Deaminase Suicide Gene
      Therapy with 5-Fluorocytosine Treatment on Hepatocellular Carcinoma Cell Line
      HepG2 In Vitro and In Vivo.
AB  - BACKGROUND: Human sulfatase-1 (Hsulf-1) is an endosulfatase that selectively
      removes sulfate groups from heparan sulfate proteoglycans (HSPGs), altering the
      binding of several growth factors and cytokines to HSPG to regulate cell
      proliferation, cell motility, and apoptosis. We investigated the role of combined
      cancer gene therapy with Hsulf-1 and cytosine deaminase/5-fluorocytosine (CD/5
      FC) suicide gene on a hepatocellular carcinoma (HCC) cell line, HepG2, in vitro
      and in vivo. METHODS: Reverse transcription polymerase chain reaction and
      immunohistochemistry were used to determine the expression of Hsulf-1 in HCC.
      Cell apoptosis was observed through flow cytometry instrument and mechanism of
      Hsulf-1 to enhance the cytotoxicity of 5-FC against HCC was analyzed in HCC by
      confocal microscopy. We also establish a nude mice model of HCC to address the
      effect of Hsulf-1 expression on the CD/5-FC suicide gene therapy in vivo.
      RESULTS: A significant decrease in HepG2 cell proliferation and an increase in
      HepG2 cell apoptosis were observed when Hsulf-1 expression was combined with the
      CD/5-FC gene suicide system. A noticeable bystander effect was observed when the
      Hsulf-1 and CD genes were co-expressed. Intracellular calcium was also increased
      after HepG2 cells were infected with the Hsulf-1 gene. In vivo studies showed
      that the suppression of tumor growth was more pronounced in animals treated with
      the Hsulf-1 plus CD than those treated with either gene therapy alone, and the
      combined treatment resulted in a significant increase in survival. CONCLUSIONS:
      Hsulf-1 expression combined with the CD/5-FC gene suicide system could be an
      effective treatment approach for HCC.

PMID- 25963363
TI  - Meta-analysis for the Association of Apolipoprotein E epsilon2/epsilon3/epsilon4
      Polymorphism with Coronary Heart Disease.
AB  - BACKGROUND: Coronary heart disease (CHD) is a multifactorial disease and is
      thought to have a polygenic basis. Apolipoprotein E (APOE) gene is one such
      candidate with its common epsilon2/epsilon3/epsilon4 polymorphism in CHD. In
      recent years, numerous case-control studies have investigated the relationship of
      APOE polymorphism with CHD risk. However, the results are confusing. METHODS: To
      clarify this point, we undertook a meta-analysis based on 14 published studies
      including 5746 CHD cases and 19,120 controls. Crude odds ratios (ORs) with 95%
      confidence intervals (CIs) were assessed for association using a random-effects
      or fixed-effects model using STATA version 10 (StataCorp LP, College Station, TX,
      USA). RESULTS: Overall, the analysis showed that carriers of APOE epsilon2 allele
      decreased risk for CHD (epsilon2 allele vs. epsilon3 allele: OR = 0.82, 95% CI:
      0.75-0.90, P < 0.001; epsilon2 carriers vs. epsilon3 carriers: OR = 0.81, 95% CI:
      0.73-0.89, P < 0.001), compared with those carrying epsilon3 allele, especially
      in Caucasian population. However, those with epsilon4 allele had a significant
      increased risk for CHD (epsilon4 allele vs. epsilon3 allele: OR = 1.34, 95% CI:
      1.15-1.57, P < 0.001), especially in Mongoloid population. Potential publication
      bias was observed in the genetic model of epsilon4 versus epsilon3, but the
      results might not be affected deeply by the publication bias. When we accounted
      for publication bias using the trim and fill method, the results were not
      materially alerted, suggesting the stability of our results. CONCLUSIONS: Taken
      together, our meta-analysis supported a genetic association between APOE gene and
      CHD. epsilon4 increased the risk of CHD, whereas epsilon2 decreased the risk of
      CHD.

PMID- 25963364
TI  - Clinical Relevance of Coronary Fractional Flow Reserve: Art-of-state.
AB  - OBJECTIVE: The objective was to delineate the current knowledge of fractional
      flow reserve (FFR) in terms of definition, features, clinical applications, and
      pitfalls of measurement of FFR. DATA SOURCES: We searched database for primary
      studies published in English. The database of National Library of Medicine (NLM),
      MEDLINE, and PubMed up to July 2014 was used to conduct a search using the
      keyword term "FFR". STUDY SELECTION: The articles about the definition, features,
      clinical application, and pitfalls of measurement of FFR were identified,
      retrieved, and reviewed. RESULTS: Coronary pressure-derived FFR rapidly assesses
      the hemodynamic significance of individual coronary artery lesions and can
      readily be performed in the catheterization laboratory. The use of FFR has been
      shown to effectively guide coronary revascularization procedures leading to
      improved patient outcomes. CONCLUSIONS: FFR is a valuable tool to determine the
      functional significance of coronary stenosis. It combines physiological and
      anatomical information, and can be followed immediately by percutaneous coronary
      intervention (PCI) if necessary. The technique of FFR measurement can be
      performed easily, rapidly, and safely in the catheterization laboratory. By
      systematic use of FFR in dubious stenosis and multi-vessel disease, PCI can be
      made an even more effective and better treatment than it is currently. The
      current clinical evidence for FFR should encourage cardiologists to use this tool
      in the catheterization laboratory.

PMID- 25963366
TI  - Myotonic dystrophy type 1 associated with white matter hyperintense lesions:
      clinic, imaging, and genetic analysis.

PMID- 25963365
TI  - Dexmedetomidine May Produce Extra Protective Effects on Sepsis-induced Diaphragm
      Injury.
AB  - OBJECTIVE: The objective was to evaluate the protective effects of
      dexmedetomidine (DEX), a selective agonist of alpha2-adrenergic receptor, on
      sepsis-induced diaphragm injury and the underlying molecular mechanisms. DATA
      SOURCES: The data used in this review were mainly from PubMed articles published
      in English from 1990 to 2015. STUDY SELECTION: Clinical or basic research
      articles were selected mainly according to their level of relevance to this
      topic. RESULTS: Sepsis could induce severe diaphragm dysfunction and exacerbate
      respiratory weakness. The mechanism of sepsis-induced diaphragm injury includes
      the increased inflammatory cytokines and excessive oxidative stress and
      superfluous production of nitric oxide (NO). DEX can reduce inflammatory
      cytokines, inhibit nuclear factor-kappaB signaling pathways, suppress the
      activation of caspase-3, furthermore decrease oxidative stress and inhibit NO
      synthase. On the basis of these mechanisms, DEX may result in a shorter period of
      mechanical ventilation in septic patients in clinical practice. CONCLUSIONS:
      Based on this current available evidence, DEX may produce extra protective
      effects on sepsis-induced diaphragm injury. Further direct evidence and more
      specific studies are still required to confirm these beneficial effects.

PMID- 25963367
TI  - A rare case of abdominal cocoon presenting as umbilical hernia.

PMID- 25963368
TI  - A typical megaesophagus: interesting imaging for diagnosis.

PMID- 25963369
TI  - Spontaneous Uterine Rupture during Late Pregnancy after High-intensity Focused
      Ultrasound.

PMID- 25963370
TI  - Chinese People's Liberation Army on Action of Fighting against Ebola in Africa:
      Implications and Challenges.

PMID- 25963371
TI  - Genetic testing: cfDNA screening for trisomy 21 tested in unselected pregnancies.

PMID- 25963372
TI  - Estimating the mutation load in human genomes.
AB  - Next-generation sequencing technology has facilitated the discovery of millions
      of genetic variants in human genomes. A sizeable fraction of these variants are
      predicted to be deleterious. Here, we review the pattern of deleterious alleles
      as ascertained in genome sequencing data sets and ask whether human populations
      differ in their predicted burden of deleterious alleles - a phenomenon known as
      mutation load. We discuss three demographic models that are predicted to affect
      mutation load and relate these models to the evidence (or the lack thereof) for
      variation in the efficacy of purifying selection in diverse human genomes. We
      also emphasize why accurate estimation of mutation load depends on assumptions
      regarding the distribution of dominance and selection coefficients - quantities
      that remain poorly characterized for current genomic data sets. 

PMID- 25963374
TI  - Chromosome biology: Diverse evolution of sex chromosomes in flies.

PMID- 25963373
TI  - Evidence for archaic adaptive introgression in humans.
AB  - As modern and ancient DNA sequence data from diverse human populations
      accumulate, evidence is increasing in support of the existence of beneficial
      variants acquired from archaic humans that may have accelerated adaptation and
      improved survival in new environments - a process known as adaptive
      introgression. Within the past few years, a series of studies have identified
      genomic regions that show strong evidence for archaic adaptive introgression.
      Here, we provide an overview of the statistical methods developed to identify
      archaic introgressed fragments in the genome sequences of modern humans and to
      determine whether positive selection has acted on these fragments. We review
      recently reported examples of adaptive introgression, grouped by selection
      pressure, and consider the level of supporting evidence for each. Finally, we
      discuss challenges and recommendations for inferring selection on introgressed
      regions. 

PMID- 25963375
TI  - Dextran sulfate sodium inhibits amyloid-beta oligomer binding to cellular prion
      protein.
AB  - Amyloid-beta peptide (Abeta), especially its oligomeric form, is believed to play
      an important role in the pathogenesis of Alzheimer's disease (AD). To this end,
      the binding of Abeta oligomer to cellular prion protein (PrP(C)) plays an
      important role in synaptic dysfunction in a mouse model of AD. Here, we have
      screened for compounds that inhibit Abeta oligomer binding to PrP(C) from
      medicines already used clinically (Mizushima Approved Medicine Library 1), and
      identified dextran sulfate sodium (DSS) as a candidate. In a cell-free assay, DSS
      inhibited Abeta oligomer binding to PrP(C) but not to ephrin receptor B2, another
      endogenous receptor for Abeta oligomers, suggesting that the drug's action is
      specific to the binding of Abeta oligomer to PrP(C) . Dextran on the other hand
      did not affect this binding. DSS also suppressed Abeta oligomer binding to cells
      expressing PrP(C) but not to control cells. Furthermore, while incubation of
      mouse hippocampal slices with Abeta oligomers inhibited the induction of long
      term potentiation, simultaneous treatment with DSS restored the long-term
      potentiation. As DSS has already been approved for use in patients with
      hypertriglyceridemia, and its safety in humans has been confirmed, we propose
      further analysis of this drug as a candidate for AD treatment. Amyloid-beta
      peptide (Abeta) oligomer-binding to cellular prion protein (PrP(C) ) is important
      in synaptic dysfunction in Alzheimer's disease (AD). We found here that dextran
      sulfate sodium (DSS) inhibits Abeta oligomer binding to PrP(C) . Simultaneous
      treatment of hippocampal slices with DSS restored long-term potentiation (LTP) in
      the presence of Abeta oligomers. Since DSS has already been approved for clinical
      use, we propose this drug is a candidate drug for AD treatment.

PMID- 25963376
TI  - Reply to the letter: "The diagnostic value of MRI in pediatric chronic
      inflammatory demyelinating polyradiculoneuropathy".

PMID- 25963377
TI  - Widespread white matter but focal gray matter alterations in depressed
      individuals with thoughts of death.
AB  - BACKGROUND: Past work demonstrates that depressed individuals with suicidal
      thoughts or behaviors exhibit specific neuroanatomical alterations. This may
      represent a distinct phenotype characterized by specific findings on
      neuroimaging, but it is unclear if these findings extend to individuals with
      milder thoughts of death. We examined this question in outpatients with recurrent
      Major Depressive Disorder not receiving antidepressant treatment. METHODS: We
      examined 165 subjects: 53 depressed without thoughts of death, 21 depressed with
      thoughts of death, and 91 healthy comparison subjects. Participants completed 3T
      cranial MRI, including anatomical and diffusion tensor imaging acquisitions.
      Automated methods measured regional gray matter volumes in addition to cortical
      thickness. White matter analyses examined diffusion measures within specific
      fiber tracts and included voxelwise comparisons. RESULTS: After adjustment for
      multiple comparisons, the depressed group with thoughts of death did not exhibit
      differences in regional gray matter volume, but did exhibit reduced cortical
      thickness in frontoparietal regions and the insula. This depressed group with
      thoughts of death also exhibited widespread white matter differences in
      fractional anisotropy and radial diffusivity. These differences were observed
      primarily in posterior parietal white matter regions and central white matter
      tracts adjacent to the basal ganglia and thalamus. CONCLUSIONS: Mild thoughts of
      death are associated with structural alterations in regions of the salience
      network, default mode network, and thalamocortical circuits. Further work is
      needed to understand the pathological basis of these findings.

PMID- 25963378
TI  - Energetics (and kinematics) of short shuttle runs.
AB  - PURPOSES: The energy cost of shuttle running (C netSR), over distances of 10-20
      m, was reported to increase with the shuttle speed and to decrease with the
      shuttle distance. The aims of this study were to assess C netSR over a shorter
      distance (5 m), at different speeds, and to estimate the energy cost based on a
      simple kinematic analysis (C netK). METHODS: Ten subjects (six basketball
      players, BP; four non-basketball players, NBP) performed ten shuttle runs (SR)
      with 30 s of passive recovery in-between, over a distance of 5 + 5 m (with a 180
      degrees  change of direction); these experiments were repeated at different
      speeds (range 2-3.5 m s(-1)). The values of average (v mean) and maximal (v max)
      speed during each run were determined by means of kinematic analysis and C netK
      was calculated as: 0.96[Formula: see text]. C netSR was calculated based on data
      of oxygen uptake, blood lactate concentration and distance covered. RESULTS: The
      relationships between C (J m(-1) kg(-1)) and v (m(.)s(-1)) are well described by
      C netK (all subjects) = 11.76v - 13.09, R (2) = 0.853; C netSR (BP) = 11.94v -
      12.82, R (2) = 0.636; and C netSR (NBP) = 14.09v - 14.53, R (2) = 0.738. Hence C
      netSR ~ C netK in BP, whereas C netSR > C netK in NBP (un-familiar with this
      specific motor task). DISCUSSION: The calculations proposed in this study allow
      to estimate C of short SR based on simple measures of v max and can be utilized
      to develop training protocols in basketball as well as in other team sports
      (characterized by repeated sprints over short distances).

PMID- 25963379
TI  - The interactive effect of cooling and hypoxia on forearm fatigue development.
AB  - PURPOSE: To examine the effect of separate and combined exposure to hypoxia
      [normoxia (FIO2 = 0.21) vs. moderate altitude (FIO2 = 0.13)] and temperature
      [thermoneutral (22  degrees C) vs. cold (5  degrees C)] on muscle fatigue
      development in the forearm, after repeated low-resistance contractions. METHODS:
      Eight males were exposed for 70 min to four separate conditions in a balanced
      order. Conditions were normoxic-thermoneutral (N), hypoxic-thermoneutral,
      normoxic-cold and hypoxic-cold. After 15-min seated rest, participants carried
      out intermittent dynamic forearm exercise at 15 % maximal isometric voluntary
      contraction (MVC) for eight consecutive, 5-min work bouts. Each bout was
      separated by 110 s rest during which MVC force was collected. RESULTS: When
      exposed to hypoxia and cold independently, the exercise protocol decreased MVC
      force of the finger flexors by 8.1 and 13.9 %, respectively, compared to
      thermoneutral normoxia. When hypoxia and cold were combined, the decrease in MVC
      force was 21.4 % more than thermoneutral normoxia, reflecting an additive effect
      and no interaction. EMG relative to force produced during MVC, increased by 2 and
      1.2 MUV per kg (36 and 23 % of N) for cold and hypoxia, respectively. When the
      stressors were combined the effect was additive, increasing to 3.1 MUV per kg (56
      % of N). CONCLUSION: When compared to exercise in thermoneutral normoxic
      conditions, both cold and hypoxia significantly reduce brief MVC force output.
      This effect appears to be of mechanical origin, not a failure in muscle fibre
      recruitment per se. Additionally, the reduction in force is greater when the
      stressors are combined, showing an additive effect.

PMID- 25963380
TI  - Effects of modest hyperoxia and oral vitamin C on exercise hyperaemia and
      reactive hyperaemia in healthy young men.
AB  - PURPOSE: We have argued that breathing 40 % O2 attenuates exercise hyperaemia by
      decreasing production of O2-dependent vasodilators. However, breathing 100 % O2
      attenuated endothelium-dependent vasodilatation evoked by acetylcholine and this
      effect was prevented by vitamin C, implicating reactive oxygen species (ROS). We
      have therefore used vitamin C to test the hypothesis that 40 % O2 modulates
      exercise hyperaemia and reactive hyperaemia independently of ROS. METHOD: In a
      cross-over study on 10 male subjects (21.1 +/- 0.84 years), we measured forearm
      blood flow (venous occlusion plethysmography) and calculated forearm vascular
      conductance (FVC) at rest and following static handgrip at 60 % maximum voluntary
      contraction for 2 min and following arterial occlusion for 2 min, after placebo
      or oral vitamin C (2000 mg), and when breathing air or 40 % O2. RESULT: During
      air breathing, vitamin C augmented the peak increase in FVC following static
      contraction, or release of arterial occlusion, by ~50 or 60 %, respectively (P <
      0.05). Breathing 40 % O2 in the presence of placebo attenuated post-contraction
      hyperaemia by ~25 % (P < 0.05), but had no effect on reactive hyperaemia. By
      contrast, in the presence of vitamin C, 40 % O2 attenuated the peak increase in
      FVC following static contraction, or release of arterial occlusion by ~25 and 50
      %, respectively (P < 0.05). CONCLUSION: These results indicate that in young men,
      exercise hyperaemia following strenuous muscle contraction and reactive
      hyperaemia are blunted by ROS. However, they are also consistent with the view
      that modest hyperoxia induced by breathing 40 % O2 acts independently of ROS to
      attenuate not only post-contraction hyperaemia, but also reactive hyperaemia, by
      decreasing release of O2-dependent vasodilators.

PMID- 25963381
TI  - Cost-effectiveness of a behavioral intervention for persistent urinary
      incontinence in prostate cancer patients.
AB  - OBJECTIVE: The aim of this study was to evaluate the cost-effectiveness of a
      behavioral intervention for urinary incontinence of prostate cancer patients.
      Study subjects were either participating in or eligible but declined (i.e.,
      nonparticipating) the active intervention study. METHODS: The intervention
      participating subjects were randomized into three groups, including two
      intervention groups (support and telephone groups) and a usual care reference
      group. Intervention-nonparticipating subjects were concurrently enrolled.
      Intervention effectiveness was assessed on the EQ-5D measure. The costs included
      direct healthcare cost from medical billing data, patient out-of-pocket expense,
      caregiver expense, patient loss-of-work cost, and intervention cost. We
      calculated incremental cost-effectiveness ratios (ICERs) from societal, provider,
      and patient perspectives. RESULTS: Two hundred and sixty-seven intervention
      participating and 69 intervention-nonparticipating post-cancer treatment patients
      were included. The support and telephone groups, but not the usual care group,
      had significantly higher EQ-5D index scores (0.054, p = 0.033, and 0.057, p =
      0.026, respectively) than the intervention-nonparticipating group at month 6.
      Within 6 months, intervention cost per subject was $252 and $484, respectively,
      for providers, and $564 and $203, respectively, for the support and phone group
      subjects. The final ICERs were $16,759 per quality-adjusted life year (QALY) and
      $12,561/QALY for support and telephone groups, compared with those of the
      intervention-nonparticipating group. These ICERs are much smaller than
      $50,000/QALY, the consensus threshold to determine cost-effectiveness for
      society. CONCLUSIONS: The study interventions are cost-effective in consideration
      of eligible patients who declined the interventions. The interventions can
      provide meaningful outcome improvement on urinary continence at a low cost. This
      evidence provides critical information for future health policy decision-making
      of healthcare providers and payers.

PMID- 25963382
TI  - Targeted therapies for treatment of renal cell carcinoma: recent advances and
      future perspectives.
AB  - PURPOSE: A wide variety of targeted therapies are available for the treatment of
      renal cancer that has progressed beyond the point at which surgery is a viable
      option. In addition, there are many more that are in the different stages of
      clinical trials. Here, we provide a methodical discussion of the efficacy and
      safety of targeted therapies for the treatment of advanced renal cell carcinoma.
      METHODS: We conducted a systematic literature employing the search terms: renal
      cell carcinoma targets, tyrosine kinase inhibitors, mammalian target of rapamycin
      inhibitors, and each of the drugs discussed within these papers. RESULTS: The
      identified targeted therapies work by disrupting specific signalling pathways
      involved in tumour progression, such as those responsible for angiogenesis and
      cell proliferation. Tyrosine kinase inhibitors and mammalian target of rapamycin
      inhibitors are now established classes of drugs used in the treatment of renal
      cancer, with a total of six having received regulatory approval to date
      (sorafenib, sunitinib, pazopanib, axitinib, temsirolimus, and everolimus).
      Ongoing trials are likely to result in addition to these in the near future, for
      example, tivozanib, dovitinib, and cediranib. Furthermore, in addition to these
      small molecule drugs, immunotherapies involving monoclonal antibodies against
      signalling molecules such as vascular endothelial growth factor (bevacizumab) or
      programmed death-1 (nivolumab) are receiving increasing attention. CONCLUSIONS:
      Targeted therapies have great potential for disrupting tumour progression by
      inhibiting certain signalling pathways. As our understanding of the biochemical
      pathways involved in cancer progresses, additional targets are certain to become
      apparent, expanding treatment options even further.

PMID- 25963383
TI  - Not all gleason pattern 4 prostate cancers are created equal: A study of latent
      prostatic carcinomas in a cystoprostatectomy and autopsy series.
AB  - BACKGROUND: The Gleason grading system represents the cornerstone of the
      management of prostate cancer. Gleason grade 4 (G4) is a heterogeneous set of
      architectural patterns, each of which may reflect a distinct prognostic value.
      METHODS: We determined the prevalence of the various G4 architectural patterns
      and intraductal carcinoma (IDC) in latent prostate cancer in contemporary Russian
      (n = 220) and Japanese (n = 100) autopsy prostates and in cystoprostatectomy (CP)
      specimens (n = 248) collected in Italy. We studied the association of each G4
      pattern with extraprostatic extension (EPE) and tumor volume to gain insight into
      their natural history. Presence of IDC and nine architectural features of Gleason
      grade 4 and 5 cancer were recorded. RESULTS: The prevalence of Gleason score >= 7
      PC was higher in the autopsy series (11%) compared to the CP series (6.5%, P =
      0.04). The prevalence of IDC and carcinoma with a cribriform architecture was
      2.2% and 3.4% in the autopsy series and 0.8% and 3.6% in the cystoprostatectomy
      series, respectively. In multivariable analysis, cribriform architecture was
      significantly associated with increased tumor volume (P < 0.001) and EPE
      (OR:11.48, 95%CI:2.30-57.16, P = 0.003). IDC was also significantly associated
      with EPE (OR:10.08, 95%CI:1.58-64.28, P = 0.014). Small fused glands had a strong
      negative association with EPE in the autopsy series (OR:0.06, 95%CI:0.01-0.58, P
      = 0.015). DISCUSSION: Our study revealed that in latent prostate cancer both
      cribriform architecture and IDC are uniquely associated with poor pathological
      outcome features. In contrast, Gleason score 7 (3 + 4) cancers with small-fused
      gland pattern might possibly include some prostate cancers with a more indolent
      biology.

PMID- 25963384
TI  - Application of a model based on dual-energy X-ray absorptiometry and finite
      element simulation for predicting the probability of osteoporotic hip fractures
      to a sample of people over 60 years.
AB  - The aim of this work is the application of a mechanical predictive model to a
      sample of people over 60 years of age, in order to analyze the fracture
      probability related to age and sex. A total of 223 elderly people (63 men, aged
      63-88, 72.32+/-6.10; 157 women, aged 61-89, 73.28+/-5.73) participated in the
      study. A dual-energy X-ray absorptiometry scanner was used to measure the bone
      mineral content and bone mineral density at total hip and femoral neck. The
      application of the predictive model also required a finite element simulation of
      the proximal femur, obtaining the mechanical damage and fracture probability maps
      corresponding to each sex and age groups analyzed. Statistical analysis shows
      higher values of bone mineral density, and consequently of Young's modulus, for
      men than for women. In general, a decrease of BMD is observed since 65 years old.
      The maximum mechanical damage value is always located at the femoral neck. The
      results indicate that mechanical damage tends to increase with age. Coherently
      with mechanical damage, the maximum fracture probability value is always located
      at the femoral neck and tends to increase with age. The simulation model to
      determine the probability of fracture is more complete than the simple
      measurement of bone mineral density, because provides additional information
      about mechanical properties of bone, and allows for a prospective detection of
      fracture risk. The model may be used for risk evaluation in specific patients, if
      anatomical and dual-energy X-ray absorptiometry measurements are available,
      helping us to decide about preventive pharmacological treatment for hip fracture.

PMID- 25963385
TI  - Improvement of the knee center of rotation during walking after opening wedge
      high tibial osteotomy.
AB  - Accurate measurement of the center of rotation of the knee joint is indispensable
      for prediction of joint kinematics and kinetics in musculoskeletal models.
      However, no study has yet identified the knee center of rotations during several
      daily activities before and after high tibial osteotomy surgery, which is one
      surgical option for treating knee osteoarthritis. In this study, an estimation
      method for determining the knee joint center of rotation was developed by
      applying the optimal common shape technique and symmetrical axis of rotation
      approach techniques to motion-capture data and validated for typical activities
      (walking, squatting, climbing up stairs, walking down stairs) of 10 normal
      subjects. The locations of knee joint center of rotations for injured and
      contralateral knees of eight subjects with osteoarthritis, both before and after
      high tibial osteotomy surgery, were then calculated during walking. It was shown
      that high tibial osteotomy surgery improved the knee joint center of rotation
      since the center of rotations for the injured knee after high tibial osteotomy
      surgery were significantly closer to those of the normal healthy population. The
      difference between the injured and contralateral knees was also generally reduced
      after surgery, demonstrating increased symmetry. These results indicate that
      symmetry in both knees can be recovered in many cases after high tibial osteotomy
      surgery. Moreover, the recovery of center of rotation in the injured knee was
      prior to that of symmetry. This study has the potential to provide fundamental
      information that can be applied to understand abnormal kinematics in patients,
      diagnose knee joint disease, and design a novel implants for knee joint
      surgeries.

PMID- 25963386
TI  - Effects of fatty infiltration in human livers on the backscattered statistics of
      ultrasound imaging.
AB  - Ultrasound imaging has been widely applied to screen fatty liver disease. Fatty
      liver disease is a condition where large vacuoles of triglyceride fat accumulate
      in liver cells, thereby altering the arrangement of scatterers and the
      corresponding backscattered statistics. In this study, we used ultrasound
      Nakagami imaging to explore the effects of fatty infiltration in human livers on
      the statistical distribution of backscattered signals. A total of 107 patients
      volunteered to participate in the experiments. The livers were scanned using a
      clinical ultrasound scanner to obtain the raw backscattered signals for
      ultrasound B-mode and Nakagami imaging. Clinical scores of fatty liver disease
      for each patient were determined according to a well-accepted sonographic scoring
      system. The results showed that the Nakagami image can visualize the local
      backscattering properties of liver tissues. The Nakagami parameter increased from
      0.62 +/- 0.11 to 1.02 +/- 0.07 as the fatty liver disease stage increased from
      normal to severe, indicating that the backscattered statistics vary from pre
      Rayleigh to Rayleigh distributions. A significant positive correlation
      (correlation coefficient rho = 0.84; probability value (p value) < 0.0001) exists
      between the degree of fatty infiltration and the Nakagami parameter, suggesting
      that ultrasound Nakagami imaging has potentials in future applications in fatty
      liver disease diagnosis.

PMID- 25963387
TI  - Finite element analysis of sliding distance and contact mechanics of hip implant
      under dynamic walking conditions.
AB  - An explicit finite element method was developed to predict the dynamic behavior
      of the contact mechanics for a hip implant under normal walking conditions. Two
      key parameters of mesh sensitivity and time steps were examined to balance the
      accuracy and computational cost. Both the maximum contact pressure and
      accumulated sliding distance showed good agreement with those in the previous
      studies using the implicit finite element analysis and analytical methods.
      Therefore, the explicit finite element method could be used to predict the
      contact pressure and accumulated sliding distance for an artificial hip joint
      simultaneously in dynamic manner.

PMID- 25963388
TI  - Multidisciplinary rehabilitation in ventilator-dependent patients: Call for
      action in specialized inpatient facilities.
AB  - The numbers of patients needing prolonged mechanical ventilation are growing. The
      rehabilitation programs to be implemented in specialized inpatient facilities are
      ill defined. There is a clear need to establish guidelines to define the optimal
      rehabilitation program in this setting. In this article we review the current
      evidence and propose some guidance.

PMID- 25963389
TI  - Identification of a novel amino acid racemase from a hyperthermophilic archaeon
      Pyrococcus horikoshii OT-3 induced by D-amino acids.
AB  - To date, there have been few reports analyzing the amino acid requirement for
      growth of hyperthermophilic archaea. We here found that the hyperthermophilic
      archaeon Pyrococcus horikoshii OT-3 requires Thr, Leu, Val, Phe, Tyr, Trp, His
      and Arg in the medium for growth, and shows slow growth in medium lacking Met or
      Ile. This largely corresponds to the presence, or absence, of genes related to
      amino acid biosynthesis in its genome, though there are exceptions. The amino
      acid requirements were dramatically lost by addition of D-isomers of Met, Leu,
      Val, allo-Ile, Phe, Tyr, Trp and Arg. Tracer analysis using (14)C-labeled D-Trp
      showed that D-Trp in the medium was used as a protein component in the cells,
      suggesting the presence of D-amino acid metabolic enzymes. Pyridoxal 5'-phosphate
      (PLP)-dependent racemase activity toward Met, Leu and Phe was detected in crude
      extract of P. horikoshii and was enhanced in cells grown in the medium
      supplemented with D-amino acids, especially D-allo-Ile. The gene encoding the
      racemase was narrowed down to one open reading frame on the basis of enzyme
      purification from P. horikoshii cells, and the recombinant enzyme exhibited PLP
      dependent racemase activity toward several amino acids, including Met, Leu and
      Phe, but not Pro, Asp or Glu. This is the first report showing the presence in a
      hyperthermophilic archaeon of a PLP-dependent amino acid racemase with broad
      substrate specificity that is likely responsible for utilization of D-amino acids
      for growth. 

PMID- 25963391
TI  - MicroRNA-18a enhances the radiosensitivity of cervical cancer cells by promoting
      radiation-induced apoptosis.
AB  - Evidence has demonstrated that microRNAs (miRNAs) are important in the regulation
      of cellular radiosensitivity of various types of human cancer. The aim of this
      study was to examine the role of miR-18a in regulating the radiosensitivity of
      cervical cancer, in order to understand the underlying mechanism and to assess
      the potential of miR-18a as a biomarker for predicting radiosensitivity. The
      expression of miR-18a was investigated in 48 cervical cancer patients. The
      results revealed that miR-18a expression was significantly higher in
      radiosensitive patients than in radioresistant patients by RT-qPCR (P<0.05).
      Transient transfection experiments showed that miR-18a was upregulated by the miR
      18a mimic and downregulated by the miR-18a inhibitor in the SiHa and HeLa cells.
      Without irradiation treatment, a similar growth was observed in the cells with or
      without transfection of miR-18a. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide (MTT) and Hoechst staining assays showed that miR-18a had no
      effect on the proliferation and apoptosis of cervical cancer cells after
      transfection. However, the upregulation of miR-18a suppressed the level of ataxia
      telangiectasia mutated and attenuated DNA double-strand break repair after
      irradiation, which re-sensitized the cervical cancer cells to radiotherapy by
      promoting apoptosis. Taken together, these results demonstrated that miR-18a is a
      potential molecule predictor of radiosensitivity in cervical cancer patients and
      played an important role in the response to radiotherapy.

PMID- 25963390
TI  - Mineralization defects in cementum and craniofacial bone from loss of bone
      sialoprotein.
AB  - Bone sialoprotein (BSP) is a multifunctional extracellular matrix protein found
      in mineralized tissues, including bone, cartilage, tooth root cementum (both
      acellular and cellular types), and dentin. In order to define the role BSP plays
      in the process of biomineralization of these tissues, we analyzed cementogenesis,
      dentinogenesis, and osteogenesis (intramembranous and endochondral) in
      craniofacial bone in Bsp null mice and wild-type (WT) controls over a
      developmental period (1-60 days post natal; dpn) by histology,
      immunohistochemistry, undecalcified histochemistry, microcomputed tomography
      (microCT), scanning electron microscopy (SEM), transmission electron microscopy
      (TEM), and quantitative PCR (qPCR). Regions of intramembranous ossification in
      the alveolus, mandible, and calvaria presented delayed mineralization and osteoid
      accumulation, assessed by von Kossa and Goldner's trichrome stains at 1 and 14
      dpn. Moreover, Bsp(-/-) mice featured increased cranial suture size at the early
      time point, 1 dpn. Immunostaining and PCR demonstrated that osteoblast markers,
      osterix, alkaline phosphatase, and osteopontin were unchanged in Bsp null
      mandibles compared to WT. Bsp(-/-) mouse molars featured a lack of functional
      acellular cementum formation by histology, SEM, and TEM, and subsequent loss of
      Sharpey's collagen fiber insertion into the tooth root structure. Bsp(-/-) mouse
      alveolar and mandibular bone featured equivalent or fewer osteoclasts at early
      ages (1 and 14 dpn), however, increased RANKL immunostaining and mRNA, and
      significantly increased number of osteoclast-like cells (2-5 fold) were found at
      later ages (26 and 60 dpn), corresponding to periodontal breakdown and severe
      alveolar bone resorption observed following molar teeth entering occlusion.
      Dentin formation was unperturbed in Bsp(-/-) mouse molars, with no delay in
      mineralization, no alteration in dentin dimensions, and no differences in
      odontoblast markers analyzed. No defects were identified in endochondral
      ossification in the cranial base, and craniofacial morphology was unaffected in
      Bsp(-/-) mice. These analyses confirm a critical role for BSP in processes of
      cementogenesis and intramembranous ossification of craniofacial bone, whereas
      endochondral ossification in the cranial base was minimally affected and
      dentinogenesis was normal in Bsp(-/-) molar teeth. Dissimilar effects of loss of
      BSP on mineralization of dental and craniofacial tissues suggest local
      differences in the role of BSP and/or yet to be defined interactions with site
      specific factors.

PMID- 25963393
TI  - Potentiation of the store-operated calcium entry (SOCE) induces
      phytohemagglutinin-activated Jurkat T cell apoptosis.
AB  - Store-operated Ca(2+) entry (SOCE) is the main Ca(2+) entry pathway of non
      excitable cells. In the past decade, the activation of this entry has been
      unveiled, with STIM1, a protein of the endoplasmic reticulum able to sense the
      intraluminal Ca(2+) content, and Orai1, the pore-forming unit of the Ca(2+)
      release activated Ca(2+) (CRAC) channels. When Ca(2+) ions are released from the
      endoplasmic reticulum, STIM1 proteins oligomerize and directly interact with
      Orai1 proteins, allowing the opening of the CRAC channels and a massive Ca(2+)
      ion influx known as SOCE. As Ca(2+) is involved in various cellular processes,
      the discovery of new drugs acting on the SOCE should be of interest to control
      the cell activity. By testing analogs of 2-aminoethyl diphenylborinate (2-APB), a
      well known, though not so selective effector of the SOCE, we identified methoxy
      diethylborinate (MDEB), a molecule able to potentiate the SOCE in three leukocyte
      and two breast cancer cell lines by increasing the Ca(2+) influx amplitude.
      Unlike 2-APB, MDEB does not affect the Ca(2+) pumps or the Ca(2+) release from
      the endoplasmic reticulum. MDEB could therefore represent the first member of a
      new group of molecules, specifically able to potentiate SOCE. Although not toxic
      for non-activated Jurkat T cells, it could induce the apoptosis of
      phytohemagglutinin-stimulated cells. 

PMID- 25963394
TI  - Changes in Autonomic Nervous System Activity are Associated with Changes in
      Sexual Function in Women with a History of Childhood Sexual Abuse.
AB  - INTRODUCTION: Women with histories of childhood sexual abuse (CSA) have higher
      rates of sexual difficulties, as well as high sympathetic nervous system response
      to sexual stimuli. AIM: The study aims to examine whether treatment-related
      changes in autonomic balance, as indexed by heart rate variability (HRV), were
      associated with changes in sexual arousal and orgasm function. METHODS: In study
      1, we measured HRV while writing a sexual essay in 42 healthy, sexually
      functional women without any history of sexual trauma. These data, along with
      demographics, were used to develop HRV norms equations. In study 2, 136 women
      with a history of CSA were randomized to one of three active expressive writing
      treatments that focused on their trauma, sexuality, or daily life (control
      condition). We recorded HRV while writing a sexual essay at pretreatment,
      posttreatment, and 2-week, and 1- and 6-month follow-ups; we also calculated the
      expected HRV for each participant based on the norms equations from study 1. MAIN
      OUTCOME MEASURES: The main outcome measures used were HRV, Female Sexual Function
      Index, Sexual Satisfaction Scale--Women. RESULTS: The difference between expected
      and observed HRV decreased over time, indicating that, posttreatment, CSA
      survivors displayed HRV closer to the expected HRV of a demographics-matched
      woman with no history of sexual trauma. Also, over time, participants whose HRV
      became less dysregulated showed the biggest gains in sexual arousal and orgasm
      function. These effects were consistent across condition. CONCLUSIONS: Treatments
      that reduce autonomic imbalance may improve sexual well-being among CSA
      populations.

PMID- 25963395
TI  - Epicardial phrenic nerve displacement during catheter ablation of atrial and
      ventricular arrhythmias: procedural experience and outcomes.
AB  - BACKGROUND: Arrhythmia origin in close proximity to the phrenic nerve (PN) can
      hinder successful catheter ablation. We describe our approach with epicardial PN
      displacement in such instances. METHODS AND RESULTS: PN displacement via
      percutaneous pericardial access was attempted in 13 patients (age 49+/-16 years,
      9 females) with either atrial tachycardia (6 patients) or atrial fibrillation
      triggered from a superior vena cava focus (1 patient) adjacent to the right PN or
      epicardial ventricular tachycardia origin adjacent to the left PN (6 patients).
      An epicardially placed steerable sheath/4 mm-catheter combination (5 patients) or
      a vascular or an esophageal balloon (8 patients) was ultimately successful.
      Balloon placement was often difficult requiring manipulation via a steerable
      sheath. In 2 ventricular tachycardia cases, absence of PN capture was achieved
      only once the balloon was directly over the ablation catheter. In 3 atrial
      tachycardia patients, PN displacement was not possible with a balloon; however, a
      steerable sheath/catheter combination was ultimately successful. PN displacement
      allowed acute abolishment of all targeted arrhythmias. No PN injury occurred
      acutely or in follow up. Two patients developed acute complications (pleuro
      pericardial fistula 1 and pericardial bleeding 1). Survival free of target
      arrhythmia was achieved in all atrial tachycardia patients; however, a
      nontargeted ventricular tachycardia recurred in 1 patient at a median of 13
      months' follow up. CONCLUSIONS: Arrhythmias originating in close proximity to the
      PN can be targeted successfully with PN displacement with an epicardially placed
      steerable sheath/catheter combination, or balloon, but this strategy can be
      difficult to implement. Better tools for phrenic nerve protection are desirable.

PMID- 25963396
TI  - Cardiovascular risk perception in women: true unawareness or risk miscalculation?
AB  - Assessing the 'accuracy' of cardiovascular risk perception is a worthy scientific
      goal that may lead to targeted interventions aimed at improving risk
      communication and health outcomes. Current cardiovascular risk scores, however,
      have shown poor calibration when used in populations that differ temporally
      and/or geographically from the derivation sample, limiting their reliability as
      the reference standard for absolute risk. In addition, accurately assessing risk
      awareness is challenging, with few available validated tools for effectively
      accounting for the outcomes assessed (coronary heart disease vs. cardiovascular
      disease), the time span of prediction (10-year vs. lifetime risk), and concepts
      of absolute versus relative risk. In this context, assessing patient awareness of
      the role of age as the key, non-modifiable driver of absolute risk can be
      particularly challenging. This commentary will examine each of these issues,
      providing context for the interpretation of studies on 'discordance' between
      calculated and perceived cardiovascular risk, such as the one recently published
      by Oertelt-Prigione et al. Moreover, we explore alternative approaches aimed at
      overcoming those limitations, enhancing understanding of the factors and true
      magnitude associated with such discordance.

PMID- 25963397
TI  - Advanced Gastrointestinal Diffuse Large B-Cell Lymphoma Presenting with
      Obstructive Jaundice and Very High CA 19-9 Level Mimicking Pancreatic
      Adenocarcinoma.

PMID- 25963398
TI  - Paediatric terminology in the Australian health and health-education context: a
      systematic review.
AB  - AIM: This study aimed to identify paediatric terminology used in the Australian
      health and health-education context, propose a standardized framework for
      Australian use, and compare it with a US-based framework. METHOD: Australian
      health and health-education websites were systematically searched using a novel
      hierarchical domain-specific search strategy to identify grey literature
      containing paediatric terminology. Webpages published from 2009 to February 2014,
      with a '.gov.au' or '.edu.au' domain and no advertising, were included.
      Paediatric terms were analysed with power-law distributions. Age definitions were
      grouped using a chi-squared test automatic interaction detection analysis
      (p<0.05). RESULTS: In total, 34 paediatric terms and 197 unique age definitions
      were identified in 613 webpages. Terms displayed a language distribution,
      although definitions had semantic and lexical ambiguity. Age definitions were
      divided into four statistically different groups (F=245.3, p<0.001). Four
      paediatric terms with distinct age definitions were proposed based on Australian
      data: 'infant: 0 to <1 year', 'early childhood: 1 year to <5 years', 'child: 5
      years to <13 years', and 'young person: 13 years to <22 years'. These
      recommendations were broader than the US-based comparison. INTERPRETATION: This
      is a starting point for standardizing Australian paediatric terminology, and a
      method for exploring paediatric terminology in other countries.

PMID- 25963399
TI  - Applicability of the Telephone Interview for Cognitive Status (Modified) in a
      community sample with low education level: association with an extensive
      neuropsychological battery.
AB  - OBJECTIVE: To explore the applicability of a Portuguese (PT) version of the
      Telephone Interview for Cognitive Status (TICS), with a delayed recall item
      [modified (M)], here termed TICSM-PT, against an extensive (in-person) battery of
      neuropsychological instruments, in a sample of older individuals with low
      educational level and without clinically manifest/diagnosed cognitive impairment.
      METHODS: Following translation/back-translation and pilot testing in 33 community
      dwellers, 142 community dwellers aged 52 to 84 years (mean = 67.45, SD = 7.91)
      were selected from local health care centres for the study (convenience sampling;
      stratified age and gender). Cronbach's alpha was used to assess internal
      consistency, and convergent validity was evaluated through the correlation
      between TICSM-PT and the Mini Mental State Examination (MMSE), as well as with a
      comprehensive battery of cognitive instruments. Divergent/discriminant validity
      was assessed through a battery of psychological instruments. The receiver
      operating curve was determined for TICSM-PT to classify participants with and
      without possible indication of cognitive impairment. RESULTS: TICSM-PT showed a
      satisfactory internal consistency (Cronbach's alpha = 0.705), convergent validity
      and discriminant validity. TICSM-PT presented a positive association with the
      global cognitive measures Mini Mental State Examination and the Montreal
      Cognitive Assessment, and also with most neuropsychological parameters. Receiver
      operating curve curves presented a sensitivity of 90.6% and specificity of 73.7%.
      The area under the curve statistic yielded a threshold score equal or below 13.5
      for cognitive impairment. CONCLUSION: TICSM-PT is a practical tool for rapid
      cognitive assessment among older individuals with low educational background.

PMID- 25963400
TI  - Is preoperative paranasal sinus computed tomography necessary for every patient
      undergoing septoplasty?
AB  - BACKGROUND: The aim of this study was to determine whether anterior rhinoscopy
      (AR), nasal endoscopy (NE) and paranasal sinus computed tomography (PNS CT) can
      predict other sinonasal obstructive pathologies in the setting of nasal septal
      deviation (NSD), and to evaluate the impact of preoperative PNS CT on the
      decision for a surgical procedure in patients with NSD. METHODS: A total of 262
      patients with NSD were evaluated using AR, NE, PNS CT, and the visual analogue
      scale (VAS) for nasal obstruction. The diagnostic values of AR, NE, and PNS CT
      for sinonasal obstructive pathologies, and the impact of preoperative PNS CT on
      the decision for a surgical procedure in patients with NSD were evaluated.
      RESULTS: PNS CT showed concomitant nasal pathologies in the 62 of 262 patients
      (23.6%) with NSD. Positive predictive value (PPV) and negative predictive value
      (NPV) of NE for concomitant nasal pathologies were 0.75 and 0.069, respectively.
      The sensitivity of NE for sinonasal pathologies was significantly higher in the
      patients with mild NSD than in the patients with moderate-severe NSD. The
      decision for a surgical procedure was changed in 22 of 262 (8.3%) patients after
      a PNS CT. CONCLUSION: We recommend performing preoperative PNS CTs on patients in
      whom septoplasty is planned, if they have obstructive middle turbinate
      hypertrophy, if one is unable to evaluate the middle meatus and posterior nasal
      cavity because of an anteriorly severe deviation or a nasal polyp, and in
      patients with chronic sinusitis based on clinical and endoscopic findings.

PMID- 25963401
TI  - On resin synthesis and cross-linking of collagen peptides containing the advanced
      glycation end-product pyrraline via Maillard condensation.
AB  - Glycation and its products cause a host of pathological conditions but their
      exact roles are yet to be determined. Pyrraline, a key product of glycation, and
      a novel pyrraline-derived cross-link have been incorporated into collagenous
      peptides via Maillard condensations performed on resin-bound peptide sequences. 

PMID- 25963402
TI  - The implication of long-lasting insecticide-treated net use in the resurgence of
      malaria morbidity in a Senegal malaria endemic village in 2010-2011.
AB  - BACKGROUND: Although the burden of malaria has significantly declined in recent
      years in sub-Saharan Africa through the widespread use of long-lasting
      insecticide treated bed-nets (LLINs) and artemisinin-based combination therapy,
      resurgence of malaria is observed in some settings after several years of LLINs
      use. This study aimed to assess if LLINs use remains protective against malaria
      during a period of resurgence of malaria morbidity in Dielmo, a rural village of
      Senegal. METHODS: In July 2008, LLINs were offered to all villagers and lately in
      July 2011, LLINs were renewed. A longitudinal study was conducted between July,
      2010 and December, 2011 among inhabitants of the village of Dielmo to identify
      all episodes of fever. Thick smears stained with Giemsa were done for every
      febrile villager and malaria attacks were treated with combination of Artesunate
      plus Amodiaquine. Cross-sectional surveys were also conducted at the end of the
      rainy season (October 2010 and November 2011) to assess asymptomatic carriage. A
      survey on LLINs use was done every quarter of the year. A random-effect logistic
      regression was used to assess the effect of LLINs use on the risk of having a
      malaria attack after adjusting for the main risk factors. RESULTS: The study
      population included 449 individuals corresponding to a total of 2140
      observations. One hundred and fifteen (115) clinical malaria attacks attributed
      to P. falciparum (cases) have been recorded over the study period. Most of the
      malaria cases occurred in October-December 2010 (49/115 i.e. 43%) and among
      adults aged 15 years and over (50/115, i.e. 43%). During the study period, the
      use of LLINs was 61% among non-malaria cases and only 42% among malaria clinical
      cases but differenced according to age group. After adjusting on gender, age,
      rainfall and LLINs replacement, we found that LLINs use (AOR [95%CI] = 0.40
      [0.25; 0.62], p < 0.001) remained a protective factor against malaria attacks
      during the study period. CONCLUSION: LLINs use remains effective to reduce
      malaria burden. These results highlight the need to pursue LLINs implementation
      in the current context of malaria elimination and to provide positive incentives
      to increase its use in the population.

PMID- 25963403
TI  - Lessons from very severe, refractory, and fatal primary autoimmune hemolytic
      anemias.

PMID- 25963405
TI  - Antipsychotics as antidepressants.
AB  - Three second-generation antipsychotic (SGA) agents have received FDA approval for
      adjunctive treatment, to antidepressant, of major depressive disorder:
      quetiapine, aripiprazole, and olanzapine. Additionally, quetiapine and lurasidone
      have been approved for the treatment of bipolar depression. There are data
      suggesting that quetiapine is effective for major depressive disorder as
      monotherapy. These agents are effective for depression only at subantipsychotic
      doses. Receptor profiles predict that all SGA will have anxiolytic effects as
      subantipsychotic doses but that all will be dysphorogenic at full antipsychotic
      doses (i.e., produce a depression-like clinical picture). The antidepressant
      effect appears to be unique to some agents, with direct evidence of insignificant
      antidepressant action for ziprasidone. Three general principles can guide the use
      of antipsychotics as antidepressants: (i) All SGAs may have anxiolytic effects;
      (ii) full antipsychotic doses are dysphorogenic, and therefore, subantipsychotic
      doses are to be used; and (iii) SGAs do not have a general antidepressant effect,
      rather, this appears to be unique to quetiapine and aripiprazole, and possibly
      lurasidone. 

PMID- 25963404
TI  - Flaxseed modulates inflammatory and oxidative stress biomarkers in cystic
      fibrosis: a pilot study.
AB  - BACKGROUND: Cystic fibrosis (CF) leads to advanced lung disease despite
      aggressive care. Persistent inflammation and oxidative stress contribute to
      exacerbations and disease progression. Flaxseed (FS), a dietary botanical
      supplement with high fiber, lignan phenolics, and omega-3 fatty acids has anti
      inflammatory and antioxidant properties in murine models of acute and chronic
      lung injury. This pilot study was designed to determine whether CF patients could
      tolerate FS, evaluate circulating FS metabolites, and study biomarkers of lung
      damage, as a prelude to studying clinical outcomes. METHODS: 10 CF patients and 5
      healthy volunteers consumed 40 g of FS daily for 4 weeks with safety and
      tolerability being assessed. Urine was evaluated for systemic oxidative stress
      and plasma for FS metabolites (enterolignans) and cytokine levels. Buccal swabs
      were analyzed for gene expression of Nrf2-regulated antioxidant enzymes including
      Heme Oxygenase-1 (HO-1) and NAD(P)H Quinone Oxidoreductase 1 (NQO1). RESULTS: All
      subjects completed the study without serious adverse events. Plasma levels of
      enterolignans were detectable in both healthy controls and CF volunteers. CF
      patients were stratified based on plasma enterolignan levels after 2 weeks of FS
      administration into high- (174 to 535 nM ED and 232 to 1841 nM EL) and low- (0 to
      32 nM ED and 0 to 40 nM EL) plasma lignan cohorts. The low enterolignan level
      cohort experienced a statistically significant drop in urinary inflammatory IsoP
      and plasma TNFalpha levels, while demonstrating higher average NQO1 mRNA levels
      in buccal epithelium compared to high-lignan patients. CONCLUSIONS: This pilot
      study demonstrated that FS is tolerated by CF patients. FS metabolites could be
      detected in the plasma. Future studies will assess appropriate dosing and target
      populations for FS, while exploring clinical outcomes. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT02014181 .

PMID- 25963406
TI  - A novel EYA4 mutation causing hearing loss in a Chinese DFNA family and genotype
      phenotype review of EYA4 in deafness.
AB  - BACKGROUND: Hereditary hearing loss is a heterogeneous class of disorders showing
      various patterns of inheritance and involving many genes. Mutations in the EYA4
      gene are responsible for postlingual, progressive, autosomal dominant hearing
      loss at the DFNA10 locus. METHODS: We report on a Chinese family with
      sensorineural, progressive hearing loss. Next-generation sequencing (NGS) was
      conducted using DNA samples from this family. A candidate mutation was confirmed
      by Sanger sequencing. A detailed genotype and phenotype analysis of EYA4 in
      deafness is provided. RESULTS: NGS revealed an insertion mutation c.544_545insA
      in exon 8 of EYA4 in all affected family members. This insertion created a
      frameshift resulting in a stop codon at position 221 (p.F221X). The p.F221X
      frameshift mutation cosegregated with hearing loss in the family. Audiograms of
      affected family members are flat or sloping, differing from the characteristic
      "cookie bite" audiogram and the mutation is localized in a different region of
      the eyaHR in EYA4. CONCLUSIONS: We identified a novel frameshift mutation in the
      EYA4 gene. Our results enrich the mutational spectrum of EYA4 and highlight the
      complexity of the DFNA10 genotypes and phenotypes. Using NGS techniques to
      establish a database of common mutations in patients with hearing loss and
      further data accumulation will contribute to the early diagnosis and development
      of fundamental therapies for hereditary hearing loss.

PMID- 25963407
TI  - Probiotics as beneficial agents in the management of diabetes mellitus: a
      systematic review.
AB  - Probiotics have been suggested to play an important role in the management of
      diabetes. We conducted a systematic review on the role of probiotics in
      modulating parameters related to diabetes in animal and human experiments. We
      searched Pubmed, Scopus and Cochrane central until June 2014, concerning the
      effects of probiotics on hyperglycemia, hyperinsulinemia and their anti-diabetic
      efficacies by modulating the activities of proinflammatory and antioxidant
      factors. Our initial search retrieved 1120 reports. After screening titles and
      abstracts, 72 full-text articles were reviewed for eligibility. Ultimately, 33
      articles met our inclusion criteria consisting of five human and twenty eight
      animal reports. Lactobacillus strains were, in particular, used in all studies
      with or without other strains. We found that probiotics have beneficial effects
      on glycemic controls, as all human studies showed significant reductions in at
      least one of the primary outcome endpoints which were the levels of fasting
      plasma glucose, postprandial blood glucose, glycated haemoglobin, insulin,
      insulin resistance and onset of diabetes; similarly, all the animal reports,
      except for two, documented significant changes in these parameters. Regarding
      secondary outcome measures, that is, lipid profiles, pro-inflammatory and anti
      oxidant factors, only one human and one animal study failed to show any
      significant changes in any of these parameters. This systematic review generally
      demonstrated beneficial effects of the probiotic administration, especially
      Lactobacillus sub-strains, on the management of diabetes-related blood
      parameters, although, more evidence, especially from human trials, is needed to
      confirm these effects and also to conduct a meta-analysis. Copyright (c) 2015
      John Wiley & Sons, Ltd. 

PMID- 25963408
TI  - Hepatic insulin signalling is dispensable for suppression of glucose output by
      insulin in vivo.
AB  - Insulin signalling and nutrient levels coordinate the metabolic response to
      feeding in the liver. Insulin signals in hepatocytes to activate Akt, which
      inhibits Foxo1 suppressing hepatic glucose production (HGP) and allowing the
      transition to the postprandial state. Here we provide genetic evidence that
      insulin regulates HGP by both direct and indirect hepatic mechanisms. Liver
      specific ablation of the IR (L-Insulin Receptor KO) induces glucose intolerance,
      insulin resistance and prevents the appropriate transcriptional response to
      feeding. Liver-specific deletion of Foxo1 (L-IRFoxo1DKO) rescues glucose
      tolerance and allows for normal suppression of HGP and gluconeogenic gene
      expression in response to insulin, despite lack of autonomous liver insulin
      signalling. These data indicate that in the absence of Foxo1, insulin signals via
      an intermediary extrahepatic tissue to regulate liver glucose production.
      Importantly, a hepatic mechanism distinct from the IR-Akt-Foxo1 axis exists to
      regulate glucose production. 

PMID- 25963409
TI  - Enhancing Accumulation and Penetration of HPMA Copolymer-Doxorubicin Conjugates
      in 2D and 3D Prostate Cancer Cells via iRGD Conjugation with an MMP-2 Cleavable
      Spacer.
AB  - To enhance the accumulation and penetration of nanomedicines in tumor tissue, we
      developed and evaluated the biological properties of matrix metalloproteinase 2
      (MMP-2)-responsive N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer drugs and
      tumor-penetrating peptide conjugates (P-DOX-PLGLAG-iRGD). Two different spacers
      were used in the design: a lysosomally (cathepsin B) cleavable tetrapeptide GFLG
      spacer conjugated doxorubicin (DOX) to HPMA copolymer, and an MMP-2-degradable
      linker (PLGLAG) connected tumor-homing and -penetrating cyclic peptide iRGD to
      HPMA copolymer. The accumulation of DOX in P-DOX-PLGLAG-iRGD-treated monolayer
      (2D) and multilayer (3D) DU-145 prostate cancer cells was higher than that of
      control groups (P-DOX and P-DOX + iRGD). The cell cycle arrest analysis and
      cytotoxicity data demonstrated that P-DOX-PLGLAG-iRGD produced a higher G2/M
      arrest and possessed stronger cytotoxicity against DU-145 cells than P-DOX + iRGD
      or P-DOX, which was consistent with the drug uptake results. Similarly, P-DOX
      PLGLAG-iRGD demonstrated the highest penetration ability in 3D multicellular DU
      145 tumor cell spheroids. The results indicate that covalent conjugation of iRGD
      via MMP-2-sensitive bonds enhances accumulation and penetration of nanomedicines
      into tumor cell monolayers and spheroids. 

PMID- 25963411
TI  - Scoring system to distinguish uncomplicated from complicated acute appendicitis.
AB  - BACKGROUND: Non-operative management may be an alternative for uncomplicated
      appendicitis, but preoperative distinction between uncomplicated and complicated
      disease is challenging. This study aimed to develop a scoring system based on
      clinical and imaging features to distinguish uncomplicated from complicated
      appendicitis. METHODS: Patients with suspected acute appendicitis based on
      clinical evaluation and imaging were selected from two prospective multicentre
      diagnostic accuracy studies (OPTIMA and OPTIMAP). Features associated with
      complicated appendicitis were included in multivariable logistic regression
      analyses. Separate models were developed for CT and ultrasound imaging,
      internally validated and transformed into scoring systems. RESULTS: A total of
      395 patients with suspected acute appendicitis based on clinical evaluation and
      imaging were identified, of whom 110 (27.8 per cent) had complicated
      appendicitis, 239 (60.5 per cent) had uncomplicated appendicitis and 46 (11.6 per
      cent) had an alternative disease. CT was positive for appendicitis in 284
      patients, and ultrasound imaging in 312. Based on clinical and CT features, a
      model was created including age, body temperature, duration of symptoms, white
      blood cell count, C-reactive protein level, and presence of extraluminal free
      air, periappendiceal fluid and appendicolith. A scoring system was constructed,
      with a maximum possible score of 22 points. Of the 284 patients, 150 had a score
      of 6 points or less, of whom eight (5.3 per cent) had complicated appendicitis,
      giving a negative predictive value (NPV) of 94.7 per cent. The model based on
      ultrasound imaging included the same predictors except for extraluminal free air.
      The ultrasound score (maximum 19 points) was calculated for 312 patients; 105 had
      a score of 5 or less, of whom three (2.9 per cent) had complicated appendicitis,
      giving a NPV of 97.1 per cent. CONCLUSION: With use of novel scoring systems
      combining clinical and imaging features, 95 per cent of the patients deemed to
      have uncomplicated appendicitis were correctly identified as such. The score can
      aid in selection for non-operative management in clinical trials.

PMID- 25963410
TI  - Multiple oncogenic mutations related to targeted therapy in nasopharyngeal
      carcinoma.
AB  - INTRODUCTION: An increasing number of targeted drugs have been tested for the
      treatment of nasopharyngeal carcinoma (NPC). However, targeted therapy-related
      oncogenic mutations have not been fully evaluated. This study aimed to detect
      targeted therapy-related oncogenic mutations in NPC and to determine which
      targeted therapy might be potentially effective in treating NPC. METHODS: By
      using the SNaPshot assay, a rapid detection method, 19 mutation hotspots in 6
      targeted therapy-related oncogenes were examined in 70 NPC patients. The
      associations between oncogenic mutations and clinicopathologic factors were
      analyzed. RESULTS: Among 70 patients, 12 (17.1%) had mutations in 5 oncogenes: 7
      (10.0%) had v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT)
      mutation, 2 (2.8%) had epidermal growth factor receptor (EGFR) mutation, 1 (1.4%)
      had phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha
      (PIK3CA) mutation, 1 (1.4%) had Kirsten rat sarcoma viral oncogene homolog (KRAS)
      mutation, and 1 (1.4%) had simultaneous EGFR and v-Raf murine sarcoma viral
      oncogene homolog B1 (BRAF) mutations. No significant differences were observed
      between oncogenic mutations and clinicopathologic characteristics. Additionally,
      these oncogenic mutations were not associated with tumor recurrence and
      metastasis. CONCLUSIONS: Oncogenic mutations are present in NPC patients. The
      efficacy of targeted drugs on patients with the related oncogenic mutations
      requires further validation.

PMID- 25963412
TI  - The Effects of a Mobile Phone Application on Quality of Life in Patients With
      Type 1 Diabetes Mellitus: A Randomized Controlled Trial.
AB  - BACKGROUND: The combination of an increasing prevalence of diabetes mellitus and
      more people having access to smartphones creates opportunities for patient care.
      This study aims to investigate whether the use of the Diabetes Under Control
      (DBEES) mobile phone application, a digital diabetes diary, results in a change
      in quality of life for patients with type 1 diabetes mellitus (T1DM) compared
      with the standard paper diary. METHODS: In this randomized controlled open-label
      trial, 63 patients with T1DM having access to a smartphone were assigned to the
      intervention group using the DBEES application (n = 31) or the control group
      using the standard paper diary (n = 32). Primary outcome was the change in
      quality of life, as measured by the RAND-36 questionnaire, between both groups.
      Secondary outcomes included diabetes-related distress (PAID), HbA1c, frequency of
      self-monitoring blood glucose, and the usability of the diabetes application
      (SUS). RESULTS: Patients had a median age (IQR) of 33 (21) years, diabetes
      duration of 17 (16) years, and an HbA1c of 62 +/- 16 mmol/mol. No significant
      differences in the QOL, using the RAND-36, within and between both groups were
      observed after 3 months. Glycemic control, diabetes-related emotional distress,
      and frequency of self-monitoring of blood glucose remained within and between
      groups. Users reviewed the usability of DBEES with a 72 +/- 20, on a range of 0
      100. CONCLUSIONS: The use of the DBEES application in the management of patients
      with T1DM for 3 months yields no alterations in quality of life compared to the
      standard paper diary.

PMID- 25963413
TI  - Emergency birth hybrid simulation with standardized patients in midwifery
      education: implementation and evaluation.
AB  - Structured simulations have become a critical part of health professions
      education at every level, particularly for high-risk, low-incidence scenarios.
      This article describes the implementation and evaluation of a hybrid simulation
      of emergency birth situations in a graduate midwifery program. In the fall of
      2011 and spring of 2012, nurse-midwifery students twice participated in 2
      simulated emergencies-shoulder dystocia and postpartum hemorrhage-using hybrid
      simulation (a standardized patient paired with a birth task trainer). Students
      found the simulations to be realistic. The use of best practices (ie, repetitive
      practice, team learning, small group debriefing, and large group debriefing)
      enhanced the quality of the simulation experience and the learners' reflection
      about their professional skills, strengths, weaknesses, and confidence in
      managing these 2 obstetric emergencies. This article is part of a special series
      of articles that address midwifery innovations in clinical practice, education,
      interprofessional collaboration, health policy, and global health. 

PMID- 25963414
TI  - Myelin and oligodendrocyte lineage cells in white matter pathology and plasticity
      after traumatic brain injury.
AB  - Impact to the head or rapid head acceleration-deceleration can cause traumatic
      brain injury (TBI) with a characteristic pathology of traumatic axonal injury
      (TAI) and secondary damage in white matter tracts. Myelin and oligodendrocyte
      lineage cells have significant roles in the progression of white matter pathology
      after TBI and in the potential for plasticity and subsequent recovery. The
      myelination pattern of specific brain regions, such as frontal cortex, may also
      increase susceptibility to neurodegeneration and psychiatric symptoms after TBI.
      White matter pathology after TBI depends on the extent and distribution of axon
      damage, microhemorrhages and/or neuroinflammation. TAI occurs in a pattern of
      damaged axons dispersed among intact axons in white matter tracts. TAI
      accompanied by bleeding and/or inflammation produces focal regions of overt
      tissue destruction, resulting in loss of both axons and myelin. White matter
      regions with TAI may also exhibit demyelination of intact axons. Demyelinated
      axons that remain viable have the potential for remyelination and recovery of
      function. Indeed, animal models of TBI have demonstrated demyelination that is
      associated with evidence of remyelination, including oligodendrocyte progenitor
      cell proliferation, generation of new oligodendrocytes, and formation of thinner
      myelin. Changes in neuronal activity that accompany TBI may also involve myelin
      remodeling, which modifies conduction efficiency along intact myelinated fibers.
      Thus, effective remyelination and myelin remodeling may be neurobiological
      substrates of plasticity in neuronal circuits that require long-distance
      communication. This perspective integrates findings from multiple contexts to
      propose a model of myelin and oligodendrocyte lineage cell relevance in white
      matter injury after TBI. This article is part of the Special Issue entitled
      'Oligodendrocytes in Health and Disease'.

PMID- 25963415
TI  - Cannabinoid receptor 2 attenuates microglial accumulation and brain injury
      following germinal matrix hemorrhage via ERK dephosphorylation in vivo and in
      vitro.
AB  - Microglia accumulation plays detrimental roles in the pathology of germinal
      matrix hemorrhage (GMH) in the immature preterm brain. However, the underlying
      mechanisms remain poorly defined. Here, we investigated the effects of a
      cannabinoid receptor 2 (CB2R) agonist on microglia proliferation and the possible
      involvement of the mitogen-activated protein kinase (MAPK) family pathway in a
      collagenase-induced GMH rat model and in thrombin-induced rat microglia cells. We
      demonstrated that activation of CB2R played a key role in attenuating brain
      edema, neuronal degeneration, microglial accumulation and the phosphorylated
      extracellular signal-regulated kinase (p-ERK) protein level 24 h following GMH.
      In vitro, Western blot analysis and immunostaining indicated that ERK and P38
      phosphorylation levels in microglia stimulated by thrombin were decreased after
      JWH-133 (CB2R selective agonist) treatment in a concentration-dependent manner.
      Microglia proliferation (EDU + microglia) and inflammatory and oxidative stress
      responses were attenuated by UO126 (ERK pathway inhibitor) 24 h after thrombin
      stimulation, an activity that was prevented by AM630 (CB2R selective antagonist).
      Overall, these findings suggest that activation of the endocannabinoid system
      might attenuate inflammation-induced secondary brain injury after GMH in rats by
      reducing microglia accumulation through a mechanism involving ERK
      dephosphorylation. Enhancing CB2R activation is a potential treatment to slow
      down the course of GMH in preterm newborns.

PMID- 25963416
TI  - Contrasting gene expression patterns induced by levodopa and pramipexole
      treatments in the rat model of Parkinson's disease.
AB  - Whether the treatment of Parkinson's disease has to be initiated with levodopa or
      a D2 agonist like pramipexole remains debatable. Levodopa is more potent against
      symptoms than D2 agonists, but D2 agonists are less prone to induce motor
      complications and may have neuroprotective effects. Although regulation of
      plastic changes in striatal circuits may be the key to their different
      therapeutic potential, the gene expression patterns induced by de novo treatments
      with levodopa or D2 agonists are currently unknown. By studying the whole
      striatal transcriptome in a rodent model of early stage Parkinson's disease, we
      have identified the gene expression patterns underlying therapeutically
      comparable chronic treatments with levodopa or pramipexole. Despite the overall
      relatively small size of mRNA expression changes at the level of individual
      transcripts, our data show a robust and complete segregation of the transcript
      expression patterns induced by both treatments. Moreover, transcripts related to
      oxidative metabolism and mitochondrial function were enriched in levodopa-treated
      compared to vehicle-treated and pramipexole-treated animals, whereas transcripts
      related to olfactory transduction pathways were enriched in both treatment groups
      compared to vehicle-treated animals. Thus, our data reveal the plasticity of
      genetic striatal networks possibly contributing to the therapeutic effects of the
      most common initial treatments for Parkinson's disease, suggesting a role for
      oxidative stress in the long term complications induced by levodopa and
      identifying previously overlooked signaling cascades as potentially new
      therapeutic targets. 

PMID- 25963417
TI  - Neuropeptide FF receptors as novel targets for limbic seizure attenuation.
AB  - Neuropeptide Y (NPY) is a well established anticonvulsant and first-in-class
      antiepileptic neuropeptide. In this study, the controversial role of NPY1
      receptors in epilepsy was reassessed by testing two highly selective NPY1
      receptor ligands and a mixed NPY1/NPFF receptor antagonist BIBP3226 in a rat
      model for limbic seizures. While BIBP3226 significantly attenuated the
      pilocarpine-induced seizures, neither of the highly selective NPY1 receptor
      ligands altered the seizure severity. Administration of the NPFF1/NPFF2 receptor
      antagonist RF9 also significantly attenuated limbic seizure activity. To further
      prove the involvement of NPFF receptors in these seizure-modulating effects, low
      and high affinity antagonists for the NPFF receptors were tested. We observed
      that the low affinity ligand failed to exhibit anticonvulsant properties while
      the two high affinity ligands significantly attenuated the seizures. Continuous
      NPFF1 receptor agonist administration also inhibited limbic seizures whereas
      bolus administration of the NPFF1 receptor agonist was without effect. This
      suggests that continuous agonist perfusion could result in NPFF1 receptor
      desensitization and mimic NPFF1 receptor antagonist administration. Our data
      unveil for the first time the involvement of the NPFF system in the management of
      limbic seizures.

PMID- 25963418
TI  - Positive modulation of synaptic and extrasynaptic GABAA receptors by an
      antagonist of the high affinity benzodiazepine binding site.
AB  - GABAA receptors are the major inhibitory neurotransmitter receptors in the brain
      and are the target for many clinically important drugs such as the
      benzodiazepines. Benzodiazepines act at the high-affinity binding site at the
      alpha+/gamma- subunit interface. Previously, an additional low affinity binding
      site for diazepam located in the transmembrane (TM) domain has been described.
      The compound SJM-3 was recently identified in a prospective screening of ligands
      for the benzodiazepine binding site and investigated for its site of action. We
      determined the binding properties of SJM-3 at GABAA receptors recombinantly
      expressed in HEK-cells using radioactive ligand binding assays. Impact on
      function was assessed in Xenopus laevis oocytes with electrophysiological
      experiments using the two-electrode voltage clamp method. SJM-3 was shown to act
      as an antagonist at the alpha+/gamma- site. At the same time it strongly
      potentiated GABA currents via the binding site for diazepam in the transmembrane
      domain. Mutation of a residue in M2 of the alpha subunit strongly reduced
      receptor modulation by SJM-3 and a homologous mutation in the beta subunit
      abolished potentiation. SJM-3 acts as a more efficient modulator than diazepam at
      the site in the trans-membrane domain. In contrast to low concentrations of
      benzodiazepines, SJM-3 modulates both synaptic and extrasynaptic receptors. A
      detailed exploration of the membrane site may provide the basis for the design
      and identification of subtype-selective modulatory drugs. 

PMID- 25963419
TI  - Taurine, a major amino acid of oyster, enhances linear bone growth in a mouse
      model of protein malnutrition.
AB  - Oysters (Oys) contain various beneficial components, such as, antioxidants and
      amino acids. However, the effects of Oys or taurine (Tau), a major amino acid in
      Oys on bone growth have not been determined. In the present study, we evaluated
      the effects of Oys or Tau on linear bone growth in a mouse model of protein
      malnutrition. To make the protein malnutrition in a mouse, we used a low protein
      diet. Growth plate thickness was increased by Oys or Tau. Bone volume/tissue
      volume, trabecular thickness, trabecular number, connection density, and total
      porosity were also improved by Oys or Tau. Oys or Tau increased insulin-like
      growth factor-1 (IGF-1) levels in serum, liver, and tibia-growth plate.
      Phosphorylations of Janus kinase 2 (JAK2) and signal transducer and activator of
      transcription 5 (STAT5) were increased by Oys and by Tau. These findings show
      that Oys or Tau may increase growth plate thickness by elevating IGF-1 levels and
      by promoting the phosphorylations of JAK2-STAT5, and suggest that Oys or Tau are
      growth-promoting substances of potential use in the food and pharmaceutical
      industries.

PMID- 25963421
TI  - Determination of synthetic lethal interactions to provide therapeutic direction
      to end aggressive prostate cancer.

PMID- 25963420
TI  - Euduboscquella costata n. sp. (Dinoflagellata, Syndinea), an Intracellular
      Parasite of the Ciliate Schmidingerella arcuata: Morphology, Molecular Phylogeny,
      Life Cycle, Prevalence, and Infection Intensity.
AB  - The syndinean dinoflagellate Euduboscquella costata n. sp., an intracellular
      parasite of the tintinnid ciliate Schmidingerella arcuata, was discovered from
      Korean coastal water in November of 2013. Euduboscquella costata parasitized in
      about 62% of the host population, with infection intensity (= number of trophonts
      in a single host cell) ranging from 1 to 8. Based on morphology and nuclear 18S
      ribosomal RNA gene sequences, the parasite is new to science. Euduboscquella
      costata n. sp. had an infection cycle typical of the genus, but had morphological
      and developmental features that distinguished it from congeneric species. These
      features include: (1) episome of the trophont with 25-40 grooves converging
      toward the center of the shield; (2) a narrow, funnel-shaped lamina pharyngea
      extending from the margin of the episomal shield to the nucleus; (3) persistence
      of grooves during extracellular development (sporogenesis); (4) a single food
      vacuole during sporogenesis; (5) separation of sporocytes early in sporogenesis,
      regardless of type of spore formed; and (6) dinospore size (ca. 14 MUm in length)
      and shape (bulbous episome with narrower, tapering hyposome). After sporogenesis,
      E. costata produced four different types of spore that showed completely
      identical 18S rRNA gene sequences. The gene sequence was completely identical
      with a previously reported population, Euduboscquella sp. ex S. arcuata, from
      Assawoman Bay, USA, indicating that the two populations are likely conspecific.
      Favella ehrenbergii, a widely recorded tintinnid known to host Euduboscquella
      spp., co-occurred with S. arcuata, but was not infected by E. costata in field
      samples or during short-term, cross-infection experiments. 

PMID- 25963422
TI  - Circulating free DNA in plasma or serum as biomarkers of carcinogenesis in colon
      cancer.

PMID- 25963423
TI  - Molecular profiling is not the future: it is now!
AB  - Bobby Reddy speaks to Gemma Westcott, Commissioning Editor: Dr Reddy graduated
      from the UCLA School of Medicine in 1996. Shortly after, he obtained an
      internship and did his residency in Internal Medicine at Harbor UCLA Medical
      Center. He then went on to do his fellowship in Hematology and Oncology at City
      of Hope. Since then, he has been working in private practice (full and part time)
      for the past 11 years and has had an academic appointment as teaching faculty at
      Harbor UCLA. Prior to his current role, Dr Reddy worked as a senior medical
      director as Caris Life Sciences. 

PMID- 25963424
TI  - Buparlisib in breast cancer.
AB  - Buparlisib (formerly BKM 120), an oral 2,6-dimorpholino pyrimidine derivative is
      a potent pan-PI3K inhibitor causing inhibition of PI3K downstream signaling
      including downregulation of p-Akt and p-S6R and apoptosis of cancer cells.
      Buparlisib is rapidly absorbed, has more than 90% bioavailability, good blood
      brain barrier penetration and half-life of 40 h. Phase I trials have shown good
      disease control rate with tolerable toxicity profile at the recommended doses of
      100 mg. The most common adverse events noted with buparlisib are rash,
      hyperglycemia, derangement of liver functions and psychiatric events. Several
      clinical trials with buparlisib alone or in combination with chemotherapy and
      targeted therapies are underway. Buparlisib has not yet been approved for regular
      use. Further randomized trials are required before buparlisib is approved for
      treatment of breast cancer.

PMID- 25963425
TI  - The SOFT trial: a Phase III study of the dihydropyrimidine dehydrogenase
      inhibitory fluoropyrimidine S-1 and oxaliplatin (SOX) plus bevacizumab as first
      line chemotherapy for metastatic colorectal cancer.
AB  - A combination of oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX) plus
      bevacizumab has been widely used for the first-line chemotherapy of metastatic
      colorectal cancer (mCRC). S-1 is an oral fluoropyrimidine preparation that
      combines tegafur, a prodrug of 5-fluorouracil, with two modulators. Several
      studies of combination chemotherapy with oxaliplatin plus S-1 (SOX) conducted in
      Asia have reported promising efficacy and safety in patients with mCRC,
      suggesting the potential to replace mFOLFOX6. The SOFT trial (JapicCTI-090699)
      was a randomized Phase III trial designed to evaluate the noninferiority of SOX
      plus bevacizumab to mFOLFOX6 plus bevacizumab in patients with mCRC. This review
      summarizes the drug concept of S-1 and the results of clinical trials of S-1 and
      SOX in CRC and presents an overview of the SOFT trial.

PMID- 25963426
TI  - A Phase I dose-escalation study of afatinib combined with nintedanib in patients
      with advanced solid tumors.
AB  - AIMS: To evaluate the safety and maximum tolerated dose (MTD) of afatinib
      combined with nintedanib. MATERIALS & METHODS: Patients received afatinib 10-20
      mg daily plus nintedanib 150-200 mg twice daily (28-day cycle). Dose escalation
      followed a 3+3 design. RESULTS: Patients received afatinib/nintedanib: 10/150 mg
      (n = 11); 10/200 mg (n = 13; MTD); 20/200 mg (n = 4). Four patients had dose
      limiting toxicities (all grade 3): increased alanine aminotransferase
      (afatinib/nintedanib: 10/150 mg), diarrhea (10/200 mg), dehydration (20/200 mg),
      diarrhea with elevated liver enzymes (20/200 mg). Frequent treatment-related
      adverse events were diarrhea, nausea, anorexia, fatigue and vomiting. In total,
      14 patients (46.2%) had objective responses at the MTD. CONCLUSION: The MTD,
      afatinib 10 mg daily plus nintedanib 200 mg twice daily, had a manageable safety
      profile, but was considered subtherapeutic for Phase II evaluation.

PMID- 25963427
TI  - Neoadjuvant chemotherapy in patients with locally advanced gallbladder cancer.
AB  - AIM: Surgery is the only curative option for patients with gallbladder cancer
      (GBC). This study looks at the outcome of patients treated with neoadjuvant
      chemotherapy (NACT). PATIENTS & METHODS: This is retrospective analysis of the
      prospectively maintained database of patients with locally advanced GBC treated
      between February 2009 and September 2013 with NACT. Patients received gemcitabine
      platinum based regimen. RESULTS: A total of 37 patients (median age: 54 years,
      64.9% females) received NACT. Overall response rate was 67.5%. In total, 17
      patients (46%) underwent R0 resection. Median overall survival/progression-free
      survival of the whole group was 13.4/8.1 months, respectively. Patients who
      underwent surgery had a significantly better overall survival (median not reached
      vs 9.5 months) and progression-free survival (25.8 vs 5.6 months), respectively.
      CONCLUSION: NACT increases resectability and survival in patients with locally
      advanced GBC.

PMID- 25963428
TI  - Multiparameter Phase I trials: a tool for model-based development of targeted
      agent combinations--example of EVESOR trial.
AB  - Optimal development of targeted drug combinations is one of the future challenges
      to be addressed. Computerization and mathematical models able to describe
      biological phenomena and to simulate the effects of changes in experimental
      conditions may help find solutions to this issue. We propose the concept of
      'multiparameter trials', where biological, radiological and clinical data
      required for modeling purpose are collected and illustrated by the ongoing
      academic EVESOR trial. The objective of the model-based work would be the
      determination of the optimized doses and dosing schedules of everolimus and
      sorafenib, offering the maximization of the predicted modeled benefit/toxicity
      ratio in patients with solid tumors. It may embody the 'proof of concept' of
      model-based drug development of anticancer agent combinations.

PMID- 25963429
TI  - Surgery for liver metastases from breast cancer.
AB  - INTRODUCTION: Liver metastases from breast cancer (BCLM) confer poor survival.
      Liver resection in BCLM patients has been increasingly employed. AIM: We
      undertook a systematic review to evaluate the role of hepatic resection in
      patients with breast cancer metastatic to the liver. MATERIALS & METHODS: In
      total, 36 studies were overviewed. Patient populations, characteristics,
      morbidity, mortality and survival were documented. RESULTS: Median overall
      survival was 41 months. Major morbidity was rare while 30-day postoperative
      mortality was near nil. CONCLUSION: Liver surgery for BCLM can be performed with
      low mortality, acceptable morbidity and promising survival benefit in carefully
      selected patients.

PMID- 25963431
TI  - Advancing radioimmunotherapy and its future role in non-Hodgkin lymphoma.
AB  - Radioimmunotherapy is an effective treatment modality with an acceptable toxicity
      profile in both indolent B-cell non-Hodgkin lymphoma and histologic
      transformation. Its ease of administration from a patient's perspective sets it
      apart from chemoimmunotherapy regimens. It has demonstrated efficacy in a range
      of different treatment scenarios. Despite its promise as a treatment modality,
      radioimmunotherapy has been seldom used, and one of the previously available
      agents is now off the market. Radioimmunotherapy has shown impressive activity in
      both the relapsed and upfront settings in follicular lymphoma, histologic
      transformation, as consolidation after chemotherapy, and in conjunction with high
      dose chemotherapy and autologous stem cell support. Future efforts should focus
      on its optimal employment in the upfront setting for follicular lymphoma as well
      as further investigation of the promising activity in histologic transformation.

PMID- 25963430
TI  - Is carbonic anhydrase IX a validated target for molecular imaging of cancer and
      hypoxia?
AB  - The presence of hypoxia is a general feature of most solid malignancies, and
      hypoxia is considered as one of major factors for anticancer therapy failure.
      Carbonic anhydrase IX (CAIX) has been reported to be an endogenous hypoxia
      marker, CAIX monoclonal antibodies, their segments and inhibitors are developed
      for CAIX imaging. However, growing evidence indicates that CAIX expression under
      hypoxia condition may be cancer cell lines or cancer-type dependent. Here we
      review the current literature on CAIX and discuss the advantage and limitation of
      CAIX as a target for tumor hypoxia imaging. Accordingly, CAIX would be unreliable
      as a universal target for cancer and tumor hypoxia visualization.

PMID- 25963432
TI  - The role of primary endocrine therapy in older women with operable breast cancer.
AB  - A Cochrane review of randomized trials shows no difference in overall survival
      between surgery and primary endocrine therapy (PET) in older women with operable
      primary breast cancer. Most of these trials were small and unselected for
      estrogen receptor (ER) status. Evidence exists showing a significant correlation
      between the degree of ER-positivity and response and outcome in patients
      receiving PET. Although surgery remains the treatment of choice, patients with ER
      rich tumors tend to do equally well on PET. When deciding optimal therapies, co
      morbidities and frailty (which impact on the likelihood of death due to competing
      causes), patient choice, agent of choice (notably the third-generation aromatase
      inhibitors) and biology (more than just being ER-positive) should all be taken
      into account.

PMID- 25963433
TI  - The skewed balance between Tregs and Th17 in chronic lymphocytic leukemia.
AB  - While Tregs maintain self-tolerance and inhibit antitumor responses, T helper
      (Th)17 cells may enhance inflammatory and antitumor responses. The balance
      between these two important T-cell subsets has been skewed in many
      immunopathologic conditions such as autoimmune and cancer diseases. B-cell
      chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the
      western world and is characterized with monoclonal expansion of B lymphocytes.
      There is evidence which implies that the progression of CLL is associated with
      expansion of Treg and downregulation of Th17 cells. In this review, we will
      discuss about immunobiology of Treg and Th17 cells and their role in
      immunopathogenesis of CLL as well as their reciprocal changes during disease
      progression.

PMID- 25963434
TI  - Corrigendum.

PMID- 25963435
TI  - The synergistic effects of DNA-damaging drugs cisplatin and etoposide with a
      histone deacetylase inhibitor valproate in high-risk neuroblastoma cells.
AB  - High-risk neuroblastoma remains one of the most important therapeutic challenges
      for pediatric oncologists. New agents or regimens are urgently needed to improve
      the treatment outcome of this fatal tumor. We examined the effect of histone
      deacetylase (HDAC) inhibitors in a combination with other chemotherapeutics on a
      high-risk neuroblastoma UKF-NB-4 cell line. Treatment of UKF-NB-4 cells with DNA
      damaging chemotherapeutics cisplatin or etoposide combined with the HDAC
      inhibitor valproate (VPA) resulted in the synergistic antitumor effect. This was
      associated with caspase-3-dependent induction of apoptosis. Another HDAC
      inhibitor trichostatin A and a derivative of VPA that does not exhibit HDAC
      inhibitory activity, valpromide, lacked this effect. The synergism was only
      induced when VPA was combined with cytostatics targeted to cellular DNA; VPA does
      not potentiate the cytotoxicity of the anticancer drug vincristine that acts by a
      mechanism different from that of DNA damage. The VPA-mediated sensitization of
      UKF-NB-4 cells to cisplatin or etoposide was dependent on the sequence of drug
      administration; the potentiating effect was only produced either by simultaneous
      treatment with these drugs or when the cells were pretreated with cisplatin or
      etoposide before their exposure to VPA. The synergistic effects of VPA with
      cisplatin or etoposide were associated with changes in the acetylation status of
      histones H3 and H4. The results of this study provide a rationale for clinical
      evaluation of the combination of VPA and cisplatin or etoposide for treating
      children suffering from high-risk neuroblastoma. 

PMID- 25963436
TI  - [Not Available].

PMID- 25963437
TI  - Coliform bacteria isolated from recreational lakes carry class 1 and class 2
      integrons and virulence-associated genes.
AB  - AIMS: To characterize the integron-harbouring Gram-negative bacteria in
      recreational lakes, with focus on the genetic content of integrons, antimicrobial
      resistance profiles and virulence-associated genes. METHODS AND RESULTS: The
      presence and structure of integrons in coliform bacteria isolated from the water
      of four recreational lakes located in Poznan, Poland, was determined by PCR
      method. Antimicrobial resistance testing was done by disc diffusion method.
      Virulence-associated genes in integron-bearing Escherichia coli isolates were
      detected by PCR. A total of 155 integron-bearing strains of coliform bacteria
      were cultured. Sequence analysis showed the presence of dfrA7, aadA1, dfrA1
      aadA1, dfrA17-aadA5 and dfrA12-orfF-aadA2 gene cassette arrays in class 1
      integrons and dfrA1-sat2-aadA1 in class 2 integrons. Higher frequency of integron
      positive bacteria and higher antimicrobial resistance ranges were noted in colder
      months (January and November) compared with spring and summer months. The
      integron-harbouring E. coli carried up to nine virulence-associated genes, with
      the highest frequency of kpsMT (84.6%) and traT (783%), coding for group 2
      capsule and determining human serum resistance respectively. CONCLUSIONS:
      Integron-bearing multidrug resistant coliform bacteria carrying virulence genes
      are present in waters of recreational lakes. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This study presents antimicrobial resistance and virulence-associated
      genes in integron-bearing coliform bacteria present in the waters of recreational
      lakes, which showed that multidrug resistant bacteria with virulence traits might
      pose a threat to public health. Moreover, the presence of genes typical for
      enterotoxigenic and Shiga toxin-producing E. coli is a concern.

PMID- 25963438
TI  - Sutureless aortic valve prosthesis in a calcified homograft.

PMID- 25963439
TI  - On-pump coronary artery bypass graft operation: Is one crossclamp application
      better than two?
AB  - OBJECTIVES: Several factors may increase the risk of stroke during coronary
      artery bypass grafting. These include age and atherosclerosis, which are not
      modifiable, and aortic manipulation, which may be modifiable. This study reports
      our experience with variable degrees of aortic manipulation (ie, single vs double
      [partial occlusion] aortic crossclamp techniques) and its influence on rate of
      operative stroke. METHODS: We performed a retrospective review of 8497 patients
      treated with isolated on-pump coronary artery bypass grafting from 1993 to 2010.
      Demographics included an age of 66.8 +/- 10.3 years and male sex in 6548 patients
      (77.1%). Operative technique used the single aortic crossclamp in 2051 patients
      (24.1%) and the partial aortic crossclamp in 6446 patients (75.9%). To adjust for
      differences in baseline patient characteristics, 2 propensity-matched cohorts of
      1333 patients each were created using Society of Thoracic Surgeons risk
      calculator variables. RESULTS: In the unmatched cohorts, stroke occurred in 25
      patients (1.2%) in the single aortic crossclamp cohort and in 98 patients (1.5%)
      in the partial aortic crossclamp cohort (P = .320). Logistic regression analysis
      demonstrated no significant relationship between stroke and aortic occlusion
      clamp technique (single clamp odds ratio, 0.80; 95% confidence interval, 0.51
      1.24; P = .321). In the matched cohorts, stroke occurred in 16 patients (1.2%) in
      both the single and partial occlusion clamp cohorts (P = 1.00). CONCLUSIONS:
      Given the methods and limitations of the data analysis, the single and partial
      aortic crossclamp techniques result in similar rates of stroke during on-pump
      coronary artery bypass grafting.

PMID- 25963440
TI  - Acute kidney injury after Fontan completion: Risk factors and outcomes.
AB  - OBJECTIVE: Acute kidney injury (AKI) is a predictor of outcomes in heterogeneous
      populations of children undergoing cardiac surgery. We investigated its causes
      and consequences in a cohort undergoing Fontan completion, hypothesizing that
      central venous pressure is independently associated with development of AKI.
      METHODS: In this retrospective cohort study of patients undergoing Fontan (n =
      211), univariable and multivariable analyses identified factors associated with
      AKI within 3 days of surgery. Secondary analyses identified factors associated
      with hospital length of stay, and examined effects of perioperative kidney injury
      on follow-up renal function. RESULTS: Acute kidney injury occurred in 42% of
      cases (n = 89), with the following independent risk factors: mean renal perfusion
      (mean arterial minus central venous) pressure on postoperative day zero (per mm
      Hg; adjusted odds ratio [AOR] 0.83; P < .001); preoperative atrioventricular
      valve regurgitation > mild (AOR 6.78; P = .02); bypass time (per 10 minutes, AOR
      1.08; P = .04); peak inotrope score on postoperative day zero (per point, AOR
      1.17; P < .001); and preoperative pulmonary vascular resistance (per Wood unit,
      AOR 1.69; P = .04). Central venous pressure was not independently associated with
      AKI. Moderate and severe (but not mild) AKI were independently associated with
      prolonged hospital length of stay (adjusted hazard ratios, 0.56; P = .004, and
      .41; P = .006, respectively). Perioperative injury was not associated with longer
      term renal dysfunction. CONCLUSIONS: Acute kidney injury is common after Fontan
      completion and has several potentially modifiable risk factors. Moderate-to
      severe injury is associated with longer hospital length of stay but not with
      renal dysfunction at follow-up.

PMID- 25963441
TI  - Propensity scores: Methods, considerations, and applications in the Journal of
      Thoracic and Cardiovascular Surgery.
AB  - OBJECTIVE: To review the published literature using propensity scoring, describe
      shortcomings in the use of this technique, and provide conceptual background for
      understanding and correctly implementing studies that use propensity matching.
      METHODS: We survey the published statistical literature and make recommendations
      for a set of standard criteria for studies that use propensity matching. We
      evaluated adherence to these criteria in recent publications in the Journal of
      Thoracic and Cardiovascular Surgery and determined how well the standards were
      applied. RESULTS: We found that studies that use propensity matching are rarely
      documented well enough to be convincing in their results. When documentation is
      available, statistical shortcomings are common. CONCLUSIONS: Improved statistical
      practice is needed when using propensity scoring. This article suggests standard
      criteria for using this method in Journal publications.

PMID- 25963442
TI  - ATF2 alters melanocyte response and macrophage recruitment in UV-irradiated
      neonatal mouse skin.

PMID- 25963444
TI  - Automated quantitative image analysis of nanoparticle assembly.
AB  - The ability to characterize higher-order structures formed by nanoparticle (NP)
      assembly is critical for predicting and engineering the properties of advanced
      nanocomposite materials. Here we develop a quantitative image analysis software
      to characterize key structural properties of NP clusters from experimental images
      of nanocomposites. This analysis can be carried out on images captured at
      intermittent times during assembly to monitor the time evolution of NP clusters
      in a highly automated manner. The software outputs averages and distributions in
      the size, radius of gyration, fractal dimension, backbone length, end-to-end
      distance, anisotropic ratio, and aspect ratio of NP clusters as a function of
      time along with bootstrapped error bounds for all calculated properties. The
      polydispersity in the NP building blocks and biases in the sampling of NP
      clusters are accounted for through the use of probabilistic weights. This
      software, named Particle Image Characterization Tool (PICT), has been made
      publicly available and could be an invaluable resource for researchers studying
      NP assembly. To demonstrate its practical utility, we used PICT to analyze
      scanning electron microscopy images taken during the assembly of surface
      functionalized metal NPs of differing shapes and sizes within a polymer matrix.
      PICT is used to characterize and analyze the morphology of NP clusters, providing
      quantitative information that can be used to elucidate the physical mechanisms
      governing NP assembly. 

PMID- 25963443
TI  - The rise and fall of poly(ADP-ribose): An enzymatic perspective.
AB  - Human cells respond to DNA damage with an acute and transient burst in production
      of poly(ADP-ribose), a posttranslational modification that expedites damage
      repair and plays a pivotal role in cell fate decisions. Poly(ADP-ribose)
      polymerases (PARPs) and glycohydrolase (PARG) are the key set of enzymes that
      orchestrate the rise and fall in cellular levels of poly(ADP-ribose). In this
      perspective, we focus on recent structural and mechanistic insights into the
      enzymes involved in poly(ADP-ribose) production and turnover, and we highlight
      important questions that remain to be answered. 

PMID- 25963445
TI  - Why and How to Promote Adolescents' Prosocial Behaviors: Direct, Mediated and
      Moderated Effects of the CEPIDEA School-Based Program.
AB  - Prosocial behaviors are considered integral to intervention goals that seek to
      promote successful youth development. This study examines the effect of a school
      based intervention program entirely designed to promote prosocial behaviors
      called Promoting Prosocial and Emotional Skills to Counteract Externalizing
      Problems in Adolescence (Italian acronym CEPIDEA). The CEPIDEA curriculum was
      incorporated into routine educational practices and included five major
      components that reflect the personal determinants of prosocial behavior during
      adolescence. The present study assessed 151 students (48.7% female; M(age) =
      12.4) of the intervention school and 140 students (51.2% female; M(age) = 13.0)
      of the control school at three points. A multi-group latent curve analysis
      revealed that the intervention group, compared with the control group, showed an
      increase in prosocial behavior, interpersonal self-efficacy beliefs, and
      agreeableness along with a decrease in physical aggression above and beyond the
      normative developmental trend of the these variables. Participants of the
      intervention also obtained higher grades than the control group at the end of
      middle school. Moderation effects for prosocial behavior and agreeableness
      evidenced that those who benefited most from the intervention were those
      adolescents with lower normative development of prosocial behavior, low initial
      level of agreeableness, and high initial level of physical aggression. The
      results also showed that the increase of prosocial behaviors mediated the decline
      of verbal aggression in adolescents who had attended the intervention. These
      findings suggest that interventions aimed at promoting prosocial behaviors while
      having the potential to support positive outcomes may also counteract or redirect
      negative trajectories of functioning.

PMID- 25963446
TI  - Longitudinal Reciprocal Relationships Between Discrimination and Ethnic Affect or
      Depressive Symptoms Among Chinese American Adolescents.
AB  - Discrimination plays an important role in the development of ethnic minority
      adolescents. However, previous studies have often adopted a unidirectional model
      examining the influence of discrimination on adolescent development, thus leaving
      the potential reciprocal relationship between them understudied. Moreover, there
      is a dearth of studies on Chinese Americans in the discrimination literature.
      Therefore, this study aimed to examine the reciprocal relationships between
      discrimination and two measures of adolescent outcomes (i.e., ethnic affect and
      depressive symptoms) from early adolescence to emerging adulthood in Chinese
      Americans. Participants were 444 adolescents (54 % female), followed at four-year
      intervals, beginning at 7th or 8th grade (M age.wave1 = 13.03) in 2002, for a
      total of three waves. An examination of cross-lagged autoregressive models
      revealed two major findings. First, in contrast to the rejection-identification
      model, perceived discrimination at early adolescence negatively related to ethnic
      affect at middle adolescence. Conversely, ethnic affect at early adolescence also
      negatively related to discrimination at middle adolescence. These results held
      the same direction but became insignificant from middle adolescence to emerging
      adulthood. Second, perceived discrimination positively related to depressive
      symptoms across the studied developmental periods, and depressive symptoms
      positively related to perceived discrimination from middle adolescence to
      emerging adulthood. The strength of these longitudinal relationships did not
      change significantly across developmental periods or gender. These findings
      highlight the bidirectional relationship between perceived discrimination and
      adolescent outcomes; they also demonstrate the value of studying the
      discrimination experiences of Chinese Americans. 

PMID- 25963447
TI  - Novel Statistical Approach to Determine Inflammatory Bowel Disease: Patients'
      Perspectives on Shared Decision Making.
AB  - BACKGROUND: Limited information is available on patients' perspectives of shared
      decision-making practices used in inflammatory bowel disease (IBD). OBJECTIVE:
      The aim of this study was to examine patient insights regarding shared decision
      making among patients with IBD using novel statistical technology to analyze
      qualitative data. METHODS: Two 10-patient focus groups (10 ulcerative colitis
      patients and 10 Crohn's disease patients) were conducted in Chicago in January
      2012 to explore patients' experiences, concerns, and preferences related to
      shared decision making. Key audio excerpts of focus group insights were embedded
      within a 25-min online patient survey and used for moment-to-moment affect trace
      analysis. RESULTS: A total of 355 IBD patients completed the survey (ulcerative
      colitis 51 %; Crohn's disease 49 %; female 54 %; 18-50 years of age 50 %). The
      majority of patients (66 %) reported increased satisfaction when they
      participated in shared decision making. Three unique patient clusters were
      identified based on their involvement in shared decision making: satisfied,
      content, and dissatisfied. Satisfied patients (18 %) had a positive physician
      relationship and a high level of trust with their physician. Content patients (48
      %) had a moderate level of trust with their physician. Dissatisfied patients (34
      %) had a life greatly affected by IBD, a low level of trust of their physician, a
      negative relationship with their physician, were skeptical of decisions, and did
      not rely on their physician for assistance. CONCLUSION: This study provides
      valuable insights regarding patients' perceptions of the shared decision-making
      process in IBD treatment using a novel moment-to-moment hybrid technology
      approach. Patient perspectives in this study indicate an increased desire for
      shared decision making in determining an optimal IBD treatment plan.

PMID- 25963448
TI  - A 3D ex vivo mandible slice system for longitudinal culturing of transplanted
      dental pulp progenitor cells.
AB  - Harnessing mesenchymal stem cells for tissue repair underpins regenerative
      medicine. However, how the 3D tissue matrix maintains such cells in a quiescent
      state whilst at the same time primed to respond to tissue damage remains
      relatively unknown. Developing more physiologically relevant 3D models would
      allow us to better understand the matrix drivers and influence on cell-lineage
      differentiation in situ. In this study, we have developed an ex vivo organotypic
      rat mandible slice model; a technically defined platform for the culture and
      characterization of dental pulp progenitor cells expressing GFP driven by the
      beta-actin promoter (cGFP DPPCs). Using confocal microscopy we have characterized
      how the native environment influences the progenitor cells transplanted into the
      dental pulp. Injected cGFP-DPPCs were highly viable and furthermore
      differentially proliferated in unique regions of the mandible slice; in the
      dentine region, cGFP-DPPCs showed a columnar morphology indicative of expansion
      and lineage differentiation. Hence, we demonstrated the systematic capacity for
      establishing a dental pulp cell-micro-community, phenotypically modified in the
      tooth (the "biology"); and at the same time addressed technical challenges
      enabling the mandible slice to be accessible on platforms for high-content
      imaging (the biology in a "multiplex" format).

PMID- 25963449
TI  - Multiple necrotic deep wound infections associated with a subcutaneous
      immunoglobulin infusion.

PMID- 25963450
TI  - Anaphylaxis and serum sickness in patients receiving omalizumab: reviewing the
      data in light of clinical experience.

PMID- 25963451
TI  - Anaphylaxis and epinephrine in North Carolina public schools.

PMID- 25963453
TI  - [Screening: why and how].

PMID- 25963452
TI  - Insect phylogenomics.
AB  - Phylogenomics, the integration of phylogenetics with genome data, has emerged as
      a powerful approach to study the evolution and systematics of species. Recently,
      several studies employing phylogenomic tools have provided better insights into
      insect evolution. Next-generation sequencing methods are now increasingly used by
      entomologists to generate genomic and transcript sequences of various insect
      species and strains. These data provide opportunities for comparative genomics
      and large-scale multigene phylogenies of diverse lineages of insects. Phy
      logenomic investigations help us to better understand systematic and evolutionary
      relationships of insect species that play important roles as herbivores,
      predators, detritivores, pollinators and disease vectors. It is important that we
      critically assess the prospects and limitations of phylogenomic methods. In this
      review, I describe the current status, outline the major challenges and remark on
      potential future applications of phylogenomic tools in studying insect
      systematics and evolution. 

PMID- 25963454
TI  - [Characteristics of suicides in Navarra by gender (2010-2013)].
AB  - OBJECTIVE: To determine the number of suicides and the main social and
      demographic characteristics, time frames and methods involved during the period
      2010-2013 in Navarra by gender. METHODS: A study of the Electronic Clinical
      Records provided by Navarra's Healthcare Service in which suicides in Navarra are
      detailed. RESULTS: One hundred and eighty individuals committed suicide. The
      number of suicides remained stable: 41 in 2010, 51 in 2011 and 44 in 2012 and
      2013. Seventy-five point four percent were males (n=136) and 24.6 % (n=44) were
      females. In the 13 to 26 age group, 12 (92.3%) out of 13 suicides were committed
      by males. In terms of employment status, 49.3% (n=70) were pensioners. The
      highest rate of suicides was reached in summer (n=71) and spring (n=39). Monday
      was the day with the highest rate of suicides (n=37) and the time period between
      8:00 and 12:00 hours was when the highest number of suicides (n=80) took place.
      The most usual ways of committing suicide were hanging (n=80), falling from a
      height (n=41) and pharmacological overdose (n=23). Males used violent methods
      more frequently. It is necessary to highlight the fact that in some of the
      sociodemographic characteristics there was up to 60% of cases without enough
      information. CONCLUSION: The results obtained show some specific features of the
      phenomenon of suicide in Navarra that should be considered for its prevention.
      Furthermore, the implementation of effective protocols of data collection is
      recommended to develop prevention strategies.

PMID- 25963455
TI  - [Trends and social inequalities in cervical cancer and breast cancer screening in
      Madrid: Non-Commumicable Disease Risk FactorSurveillance System (SIVFRENT-A) from
      1995 to 2010].
AB  - BACKGROUND: The assessment of preventive programs is necessary to support the
      decisions made in public health. There are few research studies that evaluate the
      degree of implementation and equity of cancer screening in Spain. The objective
      was to describe trends and inequalities in cervical and breast cancer screening
      according social determinants of health. METHODS: An analysis was carried out on
      the Behavioral Risk Factor Surveillance System of Community of Madrid data,
      obtained between 1995 and 2000 from telephone surveys conducted on a population
      between ages 18 to 65, were analyzed. The years were grouped into four periods:
      P1 to P4. The trends were estimated with prevalence ratios (PR) with 95%
      confidence intervals (95% CI), obtained through generalized linear models with
      binomial family and logarithmic link. The inequalities were estimated with
      differences of proportions (DP) with 95% CI. RESULTS: An increased in mammograms
      is seen especially in women with low education (PR P4/P1: 1.93; 95%CI 1.62 to
      2.3), this trend more discreet in cytology (PR P4/P1: 1.28; 95%CI 1.11 to 1.47).
      However mammograms have not increased over in the past 5 years (PR P4/P3: 1.02;
      95% CI 0.99 to 1.04). Inequalities get better, but show an increase in the last
      period. CONCLUSIONS: All groups increase in preventative behaviors and those who
      did not, had a high prevalence from the start.Itis worth mentioning the
      stagnation of mammography in disadvantaged women in the period 2007-2010. There
      was a social gradient for preventive preventative measures, which was lower in
      the population-basedscreening (mammography) than in the opportunistic one
      (cytology).

PMID- 25963456
TI  - [Questionnaire to evaluate the importance of the family in nursing care.
      Validation of the Spanish version (FINC-NA)].
AB  - BACKGROUND: The nursing profession is focused on patient care, without forgetting
      that patients are part of a social group, the family. The aim of this study was
      the adaptation of the "Families' Importance in Nursing Care-Nurses' Attitudes"
      (FINC-NA) scale to the Spanish language and its validation. METHODS: A
      descriptive cross-sectional study was carried out, using the bidirectional
      translation method for linguistic-cultural adaptation. It was applied to the
      nursing staff in the Paediatric Department of a University Hospital in Madrid. To
      evaluate the psychometric properties of the Spanish version, reliability,
      internal consistence and construct validity were calculated. RESULTS: The sample
      consisted of 274 professionals. Cronbach's Alpha coefficient for the total scale
      was 0.864, oscillating between 0.888 and 0.769 in the subscales. The principal
      components factor analysis identified 4 factors, which explained 54.22% of total
      variance. CONCLUSIONS: The new instrument makes it possible to determine the
      importance nurses give to participation by family members and their attitude to
      involving the latter in patient care, and the possibility of involving them in
      planning. It has been adapted to the Spanish population with good psychometrics
      results and enough evidence for its use in this context.

PMID- 25963457
TI  - Cross-cultural adaptation of the Zurich Claudication Questionnaire.Validation
      study of the Spanish version.
AB  - BACKGROUND: In the last few years, instruments that measure outcomes and quality
      of life as perceived by the patient have become tools of great clinical value.
      The Zurich Claudication Questionnaire is one of the main instruments for the
      assessment of patients suffering from lumbar spinal stenosis. Nonetheless, no
      valid version has been published for use in the Spanish population. METHODS: The
      Zurich Claudication Questionnaire was translated and cross-culturally adapted to
      Spanish and the psychometric characteristics of the new version were then
      studied. Seventy-six patients were selected who were to undergo epidural steroid
      injection or were seen in the Hospital Complex of Navarre Spinal Unit. RESULTS:
      The Spanish version of the Zurich Claudication Questionnaire shows high Cronbach
      alpha internal consistency values, high reproducibility, a good correlation with
      the most important low back condition questionnaires used worldwide and good
      sensitivity for detecting clinical change in patients who undergo epidural
      steroid injection. CONCLUSION: This study resulted in a version of the Zurich
      Claudication Questionnaire or Swiss Spinal Stenosis Questionnaire translated and
      cross-culturally adapted to Spanish, with highly reliable, valid and sensitive
      psychometric characteristics. These proven properties make the Zurich
      Claudication Questionnaire available for the Spanish population, to evaluate
      outcomes and health status as perceived by patients with spinal stenosis and
      claudication syndrome.

PMID- 25963458
TI  - [Hospitalization of 780 episodes of infection in 10 Spanish emergency
      departments. Admission to conventional wards or short stay units?].
AB  - BACKGROUND: To study the clinical characteristics of patients with infection
      attending the emergency department (ED) and compare those admitted to a short
      stay unit (SSU) with those admitted to a conventional hospital ward (CHW).
      METHODS: A descriptive multicenter cross-sectional analysis of infected patients
      requiring admission from 10 ED with SSU. Data were collected for age, gender,
      comorbidities, risk factors for multiresistant pathogens, type of infection,
      sepsis criteria, microbiology and antibiotic treatment. RESULTS: We documented
      780 admitted patients, mean age 70.43 years, 31% with heart disease, 29% COPD,
      26% diabetes mellitus, 15% prior antibiotic therapy and solid neoplasm. Fifty
      four percent were respiratory infections, 22% urinary infections and 8% intra
      abdominal infections. Thirteen percent had septic syndrome and beta-lactam (64%)
      and fluoroquinolones (29%) were the most prescribed antibiotics. When comparing
      patients admitted to SSU (183) with those admitted to CHW (597), in the latter
      group there were more comorbidities (86% vs. 78%), more risk factors for
      multidrug-resistant pathogens (42% vs. 25%) and cultures from different sources
      were more frequently undertaken (80% vs. 64%) (p <0.05). CONCLUSIONS: According
      to our results, SSU may be an excellent alternative to CHW for patients with
      prevalent infection and less comorbidity and fewer risk factors for multidrug
      resistance.

PMID- 25963459
TI  - [Survival by surgical approach in patients with endometrial adenocarcinoma
      treated in Navarra in the 2001-2009].
AB  - BACKGROUND: Endometrial adenocarcinoma is the most frequent gynaecological
      neoplasia after breast cancer and represents 6% of cancers in women. The
      treatment for this disease is surgery. The majority of cases are diagnosed in
      their initial stages and surgery is curative; on other occasions it is necessary
      to add radiotherapy and chemotherapy. The classical treatment for endometrial
      adenocarcinoma is hysterectomy with double adnexectomy by laparotomy, with the
      addition of pelvic and para-aortic lymphadenectomy and omentectomy according to
      the characteristics of the case. During the last 10-15 years laparoscopy has been
      introduced in the surgical treatment of endometrial adenocarcinoma. The main aim
      of this study is to analyze the cases of endometrial adenocarcinoma treated
      surgically in the former Virgen de Camino Hospital (nowadays the Hospital Complex
      of Navarra) during 2001-2009. METHODS: Historical cohort of 444 patients with
      endometrial adenocarcinoma during 2001-2009 who received surgical treatment,
      followed four years. CONCLUSIONS: The results confirm that laparoscopy is a safe
      alternative to classical laparotomy as it does not affect either survival or time
      free of disease, in both endometrioid adenocarcinoma and non-endometrioid
      adenocarcinoma.

PMID- 25963460
TI  - Predictors of mortality and poor outcome in cancer patients with E. faecium
      bloodstream infection.
AB  - BACKGROUND: To analyze predictors of mortality and poor outcome in cancer
      patients diagnosed with E. faecium bloodstream infection. METHODS: Demographic,
      clinical and microbiological data were collected (January 1998-June 2011).
      RESULTS: After multivariate analysis, presence of a urinary catheter was
      associated with a worse 7-day prognosis, and higher mortality at discharge. A
      high Charlson index was also associated with higher 7-day mortality. CONCLUSION:
      Presence of a urinary catheter was associated with poor 7-day prognosis and
      higher mortality at discharge in the present series.

PMID- 25963461
TI  - [Neuropsychological profile of frontotemporal lobar degeneration].
AB  - Frontotemporal lobar degeneration encompasses three different syndromes, with
      clinical and pathologic commonalities, making diagnosis difficult in early
      stages. Three subtypes are recognized: frontotemporal dementia and its three
      variants, corticobasal syndrome and supranuclear palsy syndrome. The objective of
      this study is to review the neuropsychological features of each syndrome in order
      to differentiate amongst subtypes as well as from other forms of dementia. We
      review multiple studies from the literature, highlighting the main clinical
      features, neuropathology and changes in brain imaging of each syndrome.
      Subsequently, we describe the neuropsychological profile compared to other
      dementias, and how it progresses over time. Although there is an overlap amongst
      the different subtypes of frontotemporal lobar degeneration, neuropsychological
      profiles can help identify subtypes and discriminate frontotemporal lobar
      degeneration from other forms of dementia. 

PMID- 25963462
TI  - [Effectiveness of family interventions in nursing homes. A systematic review].
AB  - The process of nursing home placement can be a stressful event for both the
      dependent elderly person and the family. During admission, especially the first
      few months, the family may suffer feelings of loss, sadness, failure and guilt.
      In this context, support and guidance from health professionals are essential to
      address the needs of residents and families through effective interventions. The
      aim of this systematic review is to identify the most effective interventions to
      help families during the process of institutionalization of a relative in a
      nursing home. Two types of family interventions were identified: those that
      focused on family-staff relationship and those that focused on family support
      groups, the latter being the most effective. On the other hand, most
      interventions have an individualistic approach, focusing on the primary
      caregiver. Finally, there is a shortage of quality studies that present the
      results of family interventions in the geriatric field and also a lack of such
      studies in the Spanish context. 

PMID- 25963463
TI  - [Cervical myofascial pain syndrome. Narrative review of physiotherapeutic
      treatment].
AB  - Pain is a complex and multifactorial phenomenon that depends on the interaction
      of biopsychosocial factors. Between 15-25% of adults suffer from chronic pain at
      some point in their lives. Cervical chronic pain is considered a public health
      problem affecting 9.6% men and 21.9% women, according to the latest National
      Health Survey 2011-12. A high percentage of medical consultations due to muscle
      pain turn out to be myofascial pain syndrome (MPS). Its existence implies the
      presence of myofascial trigger points which can be latent or active throughout
      the whole population. The aim of this review is to update knowledge in the
      various therapies applied by the physiotherapist in the treatment of this
      syndrome at cervical level. From the review it appears that some of the most used
      techniques that may be useful in the short or medium term are: ischemic
      compression and/or trigger point pressure release and dry needling. Furthermore,
      various combinations of treatment modalities are used to treat this syndrome,
      taking other aspects into account, such as education. 

PMID- 25963464
TI  - [Clinical approach to chronic lumbar pain: a systematic review of recommendations
      included in existing practice guidelines].
AB  - This paper presents a systematic review of clinical practice guidelines based on
      evidence, with explicit recommendations on the treatment of chronic low back
      pain. The main objective was to analyze their content and provide a synthesis in
      order to improve the translation of this evidence into practice. The
      recommendations were analyzed and then classified by treatment; evidence level
      and strength of recommendation were identified and translated into our gradation
      system. Eight guidelines met the inclusion criteria. Exercise and back school
      treatment are shown as the best therapies. Pharmacotherapy is indicated during
      short periods of time. The guidelines analyzed show similar therapeutic
      approaches. The recommendations have been synthesized in order to allow clinical
      selection of the best treatment and avoid bad practices with their corresponding
      costs, providing a more efficient management of the patient. 

PMID- 25963465
TI  - [Diagnosis of cancer in hospital emergency services].

PMID- 25963466
TI  - [Diagnosis of cancer in hospital emergency services].

PMID- 25963467
TI  - [Diagnosis of cancer in hospital emergency services].

PMID- 25963468
TI  - [Difficulties for research collaboration between cardiologists and emergency
      service doctors].

PMID- 25963469
TI  - [Author reply. Difficulties for research collaboration between cardiologists and
      emergency service doctors].

PMID- 25963470
TI  - [Difficulties for research collaboration between cardiologists and emergency
      service doctors].

PMID- 25963471
TI  - [Opinions of healthcare professionals on the definition of severe mental
      illness].

PMID- 25963472
TI  - [Authors reply. Opinions and expectations of patients with health problems
      associated to asbestos exposure].

PMID- 25963473
TI  - [Jejunal intestinal metastases, a form of presentation of pulmonary carcinoma].
AB  - Primary tumors of the small intestine are rare, and metastatic ones are even
      rarer. It is exceptional for small bowel metastases to manifest before the
      primary tumor. The clinical presentation may require surgical resection motivated
      by intestinal perforation, hemorrhage or intestinal obstruction-subocclusion.
      Survival is scarce and generally does not exceed 20 weeks, regardless of the
      treatment performed. 

PMID- 25963474
TI  - [Multiple extraneural metastasis of glioblastoma multiforme].
AB  - INTRODUCTION: Glioblastoma multiforme is the most frequent primary tumor in the
      brain. Despite improvements in its surgical, chemotherapy and radiotherapy
      treatment, prognosis remains poor. Extracranial metastases of glioblastoma are a
      rare complication in this disease. Its appearance has been described in lung,
      liver, bone or lymph nodes. CASE REPORT: We describe the case of a 20 year-old
      patient who complained of a subacute-onset headache. In the MRI an enhancing
      right temporal lesion was detected suggesting a high grade glioma as first
      diagnosis. Surgery was performed, obtaining a gross total resection of the
      lesion. Our patient underwent adjuvant radiotherapy and chemotherapy treatment,
      according to our hospital's protocol. Five months after initial surgery our
      patient complained of chest pain and a hacking cough. A thoracic-abdominal-pelvic
      CT scan was obtained, which showed bilateral lung infiltrates with pleural
      effusion, a pancreatic nodule and several vertebral lytic lesions. The lung
      lesions were biopsied. The pathologic diagnosis was metastatic glioblastoma
      multiforme. The patient died eight months after initial diagnosis. CONCLUSION:
      Extracranial metastases of glioblastoma remain a rare event although its
      incidence is increasing, probably due to the improvement in survival among these
      patients and better imaging techniques. The mechanisms for extracranial
      dissemination of glioblastoma are not entirely known, as several theories exist
      in this regard. Physicians must be aware of this complication and keep it in mind
      as a differential diagnosis to improve the quality of life of our patients.

PMID- 25963475
TI  - [Secondary effects of topical application of an essential oil. Allergic contact
      dermatitis due to tea tree oil].
AB  - BACKGROUND: Tea tree oil is an essential oil, whose use is increasing in our
      setting, due both to its supposed medicinal effects and to its aromatic
      properties. We describe our experience with allergic contact dermatitis following
      the application of this oil. MATERIAL AND METHODS: Five patients in the last 5
      years (0.4% of all the patients studied in specialized consultation) reacted to a
      5% concentration of tea tree oil in Vaseline. RESULTS: All the patients presented
      strong reactions, and in all cases these were considered relevant. Three of them
      also reacted to oxidized d-limonene, one of the components of tea tree oil, which
      is present in our standard series. CONCLUSIONS: Different cases have been
      described in the literature on allergic contact dermatitis due to tea tree oil,
      but until recently it was infrequent in our setting. With the increased
      popularity of alternative and natural therapies we have witnessed several cases
      of sensitization to this essential oil, which had been used to treat several
      supposedly "infectious" skin diseases, but which were very probably different
      forms of dermatitis.

PMID- 25963476
TI  - Internet use, Facebook intrusion, and depression: Results of a cross-sectional
      study.
AB  - Facebook has become a very popular social networking platform today, particularly
      among adolescents and young adults, profoundly changing the way they communicate
      and interact. However, some reports have indicated that excessive Facebook use
      might have detrimental effects on mental health and be associated with certain
      psychological problems. Because previous findings on the relationship between
      Facebook addiction and depression were not unambiguous, further investigation was
      required. The main objective of our study was to examine the potential
      associations between Internet use, depression, and Facebook intrusion. A total of
      672 Facebook users took part in the cross-sectional study. The Facebook Intrusion
      Questionnaire and the Center for Epidemiologic Studies Depression Scale were
      used. For collecting the data, the snowball sampling procedure was used. We
      showed that depression can be a predictor of Facebook intrusion. Our results
      provides additional evidence that daily Internet use time in minutes, gender, and
      age are also predictors of Facebook intrusion: that Facebook intrusion can be
      predicted by being male, young age, and an extensive number of minutes spent
      online. On the basis of this study, it is possible to conclude that there are
      certain demographic - variables, such as age, gender, or time spent online - that
      may help in outlining the profile of a user who may be in danger of becoming
      addicted to Facebook. This piece of knowledge may serve for prevention purposes. 

PMID- 25963477
TI  - Validation of the Memorial Sloan-Kettering Cancer Center Nomogram to Predict
      Overall Survival After Curative Colectomy in a Chinese Colon Cancer Population.
AB  - BACKGROUND: Colon cancer nomogram designed by Memorial Sloan-Kettering Cancer
      Center (MSKCC) is an online prediction tool to predict overall survival for
      individual patient after curative resection. However, this model was never
      externally validated. We evaluated the accuracy of this nomogram in an
      independent external Chinese cohort. METHODS: Clinical data from 1005 patients
      who underwent primary curative-intent surgery at Peking University Cancer
      Hospital & Institute between 1996 and 2008 were used for external validation.
      Clinicopathologic characteristics and the performance of the MSKCC nomogram for
      prediction of overall survival were evaluated for 985 patients with complete data
      by using concordance index (C-index) and calibration plot. RESULTS: The C-index
      for the MSKCC nomogram was 0.71 in the Chinese cohort, compared with 0.67 for
      American Joint Committee on Cancer (AJCC) stage (P < .0001). This suggests that
      the nomogram discriminates overall survival better than AJCC staging system.
      Calibration plot showed a good calibration of the nomogram in the validation
      cohort. Furthermore, the MSKCC nomogram prediction illustrated the heterogeneity
      for survival of Chinese patients within each AJCC stage. CONCLUSIONS: The MSKCC
      nomogram for colon cancer provides more accurate survival predictions than the
      AJCC staging system when applied to an external Chinese cohort. The MSKCC
      nomogram improved individualized prediction of survival and may aid in more
      accurate patient counseling, selection of various treatment options, and follow
      up scheduling.

PMID- 25963479
TI  - How Often Do Patients with Localized Melanoma Attend Follow-Up at a Specialist
      Center?
AB  - BACKGROUND: Post-treatment follow-up for patients with American Joint Committee
      on Cancer (AJCC) stage I/II melanoma is believed to be important for early
      detection of disease recurrence and new primary melanomas, but comes with costs
      to both patients and healthcare providers. We aimed to determine how frequently a
      cohort of patients attended follow-up after surgical treatment at one Specialist
      Center. METHODS: We used prospectively collected data from the Melanoma Institute
      Australia (MIA) for patients with AJCC stage I/II melanoma diagnosed between
      January 2008 and December 2011. The distribution of the number of recorded follow
      up visits per patient was analyzed and compared with the number of follow-up
      visits recommended in the 2008 Australian and New Zealand Melanoma Management
      Guidelines. RESULTS: A total of 3813 patients with stage I/II melanoma were
      identified. During the first year of follow-up post-surgery, 34 % of stage I
      patients and 14 % of stage II patients had the number of follow-up visits
      recommended in the guidelines. A large proportion of melanoma patients did not
      appear to be routinely followed up at MIA, with 43.2 % of stage I patients and
      28.7 % of stage II patients having either no visit or only one visit post
      surgery. During all years of follow-up, 13.2 % of stage I patients and 4.1 % of
      stage II patients had the number of follow-up visits at the specialist center as
      recommended in the guidelines. CONCLUSIONS: The large proportion of patients who
      had fewer follow-up visits than expected suggests (i) many patients are followed
      up in clinics elsewhere, and/or (ii) post-surgical surveillance is less frequent
      in practice.

PMID- 25963478
TI  - A Phase I Dose-Escalation Trial of Single-Fraction Stereotactic Radiation Therapy
      for Liver Metastases.
AB  - BACKGROUND: There is significant interest in the use of stereotactic ablative
      radiotherapy (SABR) as a treatment modality for liver metastases. A variety of
      SABR fractionation schemes are in clinical use. We conducted a phase I dose
      escalation study to determine the maximum tolerated dose of single-fraction liver
      SABR. METHODS: Patients with liver metastases from solid tumors, for whom a
      critical volume dose constraint could be met, were treated with single-fraction
      SABR. Seven patients were enrolled to the first group, with a prescription dose
      of 35 Gy. Dose was then escalated to 40 Gy in a single fraction, and seven more
      patients were treated at this dose level. Patients were followed for toxicity and
      underwent serial imaging to assess lesion response and local control. RESULTS:
      Fourteen patients with 17 liver metastases were treated. There were no dose
      limiting toxicities observed at either dose level. Nine of the 13 lesions
      assessable for treatment response showed a complete radiographic response to
      treatment; the remainder showed partial response. Local control of irradiated
      lesions was 100 % at a median imaging follow-up of 2.5 years. Two-year overall
      survival for all patients was 78 %. CONCLUSIONS: For selected patients with liver
      metastases, single-fraction SABR at doses of 35 and 40 Gy is tolerable and shows
      promising signs of efficacy at intermediate follow-up.

PMID- 25963480
TI  - Levels of Alternatively Spliced Tissue Factor in the Plasma of Patients with
      Pancreatic Cancer May Help Predict Aggressive Tumor Phenotype.
AB  - BACKGROUND: Circulating ('blood-borne') tissue factor (TF) is implicated in the
      pathogenesis of several chronic conditions, most notably cardiovascular disease,
      diabetes, and cancer. Full-length TF is an integral membrane protein, while
      alternatively spliced TF (asTF) can be secreted and, owing to its unique C
      terminus, selectively detected in bio-specimens. The predictive and/or prognostic
      value of asTF in the circulation is unknown. In a retrospective study, we
      measured levels of circulating asTF in healthy subjects and individuals with
      acute coronary syndrome (ACS), diabetes mellitus (DM), ongoing ACS + DM, and
      pancreatic ductal adenocarcinoma (PDAC). METHODS: The prototype-tailored
      procedure (Diagnostica Stago) was used to measure asTF in plasma from 205
      subjects. RESULTS: There was no significant difference between the proportion of
      healthy subjects with asTF >=200 pg/mL and those with ACS, DM, or ACS + DM. The
      proportion of pancreatic cancer patients (n = 43; PDAC: 42; pancreatic
      neuroendocrine tumor: 1) with asTF levels >=200 pg/mL was significantly higher
      than in healthy subjects; asTF levels >=200 pg/mL were detected more often in
      patients with unresectable disease irrespective of initial evaluation and/or
      preoperative carbohydrate antigen 19-9 (CA19-9) levels. CONCLUSIONS: While asTF
      levels >=200 pg/mL are not observed with increased frequency in patients with ACS
      and/or DM, they do occur more frequently in the plasma of patients with
      pancreatic cancer and are associated with lower likelihood of tumor
      resectability, irrespective of the preoperative diagnosis. asTF may thus have
      utility as a novel marker of aggressive pancreatic tumor phenotype.

PMID- 25963481
TI  - Evaluation of food effect on the oral bioavailability of pradigastat, a
      diacylglycerol acyltransferase 1 inhibitor.
AB  - Pradigastat, a diacylglycerol acyltransferase 1 inhibitor, is being developed for
      the treatment of familial chylomicronemia syndrome. The results of two studies
      that evaluated the effect of food on the oral bioavailability of pradigastat
      using randomized, open-label, parallel group designs in healthy subjects
      (n=24/treatment/study) are presented. In study 1, a single dose of 20 mg
      pradigastat was administered under the fasted condition or with a high-fat meal.
      In study 2, a single dose of 40 mg pradigastat was administered under the fasted
      condition or with a low- or high-fat meal. At the 20 mg dose, the pradigastat
      Cmax and AUClast increased by 38% and 41%, respectively, with a high-fat meal.
      When 40 mg pradigastat was administered with a low-fat meal, the Cmax and AUClast
      increased by 8% and 18%, respectively, whereas with a high-fat meal the increase
      was 20% and 18%, respectively. The population pharmacokinetic analysis with the
      pooled data from 13 studies indicated that administration of pradigastat with a
      meal resulted in an increase of 30% in both the Cmax and AUC parameters. Based on
      these results, food overall increased pradigastat exposure in the range of less
      than 40%, which is not considered clinically significant. Both 20 and 40 mg doses
      of pradigastat were well tolerated under fasted or fed conditions.

PMID- 25963482
TI  - Effect of Intramuscular Adipose Tissue Content on Prognosis in Patients
      Undergoing Hepatocellular Carcinoma Resection.
AB  - BACKGROUND: It has recently been reported that myosteatosis, the infiltration of
      fat in skeletal muscle, is associated with insulin resistance and type 2 diabetes
      mellitus. The present study investigated the effect of skeletal muscle fat
      accumulation on short- and long-term outcomes following partial hepatectomy for
      hepatocellular carcinoma (HCC) and aimed to identify prognostic factors. METHODS:
      The records of 141 HCC patients who underwent hepatectomy were retrospectively
      reviewed. Clinicopathological and outcome data from 71 patients with high
      intramuscular adipose tissue content (IMAC) were compared with those from 70
      patients with low IMAC. RESULTS: The 5-year overall survival rate was 46% among
      patients with high IMAC and 75% among those with low IMAC. The 5-year disease
      free survival rates in these groups were 18 and 38%, respectively. Multivariate
      analysis revealed that high IMAC was predictive of an unfavorable prognosis. High
      IMAC was significantly correlated with liver dysfunction, higher intraoperative
      blood loss, the need for blood transfusion, and comorbid diabetes mellitus.
      CONCLUSIONS: Greater fat accumulation in skeletal muscle was predictive of worse
      overall survival after partial hepatectomy in patients with HCC, even with
      adjustment for other known predictors. The identification of patients with
      greater skeletal muscle fat accumulation before hepatectomy could permit early
      preventive strategies to maintain muscle quality and thus improve prognosis and
      patient selection for hepatectomy.

PMID- 25963483
TI  - The End TB Strategy : India can blaze the trail.

PMID- 25963484
TI  - Responding to the ebola virus disease in West Africa: Lessons for India.

PMID- 25963485
TI  - Early neurological deterioration, easy methods to detect it.

PMID- 25963486
TI  - Exudative pleural effusion in chronic kidney disease: An aetiological dilemma.

PMID- 25963487
TI  - Biomarkers for the diagnosis of bacterial infections: in pursuit of the 'Holy
      Grail'.

PMID- 25963488
TI  - Vitamin A as a key regulator of obesity & its associated disorders: Evidences
      from an obese rat model.
AB  - During the last century, vitamin A has evolved from its classical role as a fat
      soluble vitamin and attained the status of para-/autocrine hormone. Besides its
      well-established role in embryogenesis, growth and development, reproduction and
      vision, vitamin A has also been implicated in several other physiological
      processes. Emerging experimental evidences emphasize adipose tissue as an active
      endocrine organ with great propensity to continuous growth (throughout life). Due
      to various genetic and lifestyle factors, excess energy accumulates in adipose
      tissue as fat, resulting in obesity and other complications such as type 2
      diabetes, hypertension, and cardiovascular disease. Recent in vitro and in vivo
      studies have shed light on vitamin A metabolites; retinaldehyde and retinoic acid
      and participation of their pathway proteins in the regulation of adipose tissue
      metabolism and thus, obesity. In this context, we discuss here some of our
      important findings, which establish the role of vitamin A (supplementation) in
      obesity and its associated disorders by employing an obese rat model; WNIN/Ob
      strain. 

PMID- 25963490
TI  - Predictors of early neurological deterioration in patients with acute ischaemic
      stroke with special reference to blood urea nitrogen (BUN)/creatinine ratio &
      urine specific gravity.
AB  - BACKGROUND & OBJECTIVES: Early neurological deterioration (END) occurs in about
      20 to 40 per cent of patients with acute ischaemic stroke and results in
      increased mortality and functional disability. In recent studies relative
      dehydration has been found to be associated with END in patients with acute
      ischaemic stroke. This study was conducted to identify factors useful for
      predicting END and to assess the role of blood urea nitrogen/creatinine ratio
      (BUN/creatinine) and urine specific gravity (USG) as predictors of END in
      patients with acute ischaemic stroke. METHODS: The present study was an
      observational prospective study. Various parameters comprising demographic,
      clinical, laboratory and radiological variables along with stroke severity were
      assessed and studied as predictors of early neurological deterioration in 114
      consecutive patients presenting to the Emergency department during 2012.
      BUN/creatinine >15 and USG >1.010 were studied as markers of relative dehydration
      contributing to END. RESULTS: Of the 114 patients enrolled in the study, END was
      observed in 25 (21.9%) patients. National Institutes Health Stroke Scale score
      (NIHSS) >= 12 at admission was found to be an independent risk factor for END.
      Amongst markers of relative dehydration, BUN/creatinine >15 at admission was
      found to be an independent risk factor for END, as also USG >1.010. Also,
      cerebral oedema and size of hypodensity >1/3 rd of the middle cerebral artery
      territory on cranial CT were observed to be independent risk factors for END.
      INTERPRETATION & CONCLUSIONS: Our study findings highlighted a possible
      association of relative dehydration, as indicated by BUN/creatinine ratio >15,
      with END along with other parameters like stroke severity at presentation, extent
      of hypodensity >1/3 rd of the middle cerebral artery (MCA) territory and cerebral
      oedema. Dehydration being a treatable condition, the use of BUN/creatinine >15 as
      a marker of relative dehydration, can be helpful in detecting patients with
      dehydration early and thus play a role in preventing END.

PMID- 25963491
TI  - Utility of adenosine deaminase (ADA), PCR & thoracoscopy in differentiating
      tuberculous & non-tuberculous pleural effusion complicating chronic kidney
      disease.
AB  - BACKGROUND & OBJECTIVES: Pleural effusion is a common occurrence in patients with
      late-stage chronic kidney disease (CKD). In developing countries, many effusions
      remain undiagnosed after pleural fluid analysis (PFA) and patients are
      empirically treated with antitubercular therapy. The aim of this study was to
      evaluate the role of adenosine deaminase (ADA), nucleic acid amplification tests
      (NAAT) and medical thoracoscopy in distinguishing tubercular and non-tubercular
      aetiologies in exudative pleural effusions complicating CKD. METHODS: Consecutive
      stage 4 and 5 CKD patients with pleural effusions underwent PFA including ADA and
      PCR [65 kDa gene; multiplex (IS6110, protein antigen b, MPB64)]. Patients with
      exudative pleural effusion undiagnosed after PFA underwent medical thoracoscopy.
      RESULTS: All 107 patients underwent thoracocentesis with 45 and 62 patients
      diagnosed as transudative and exudative pleural effusions, respectively. Twenty
      six of the 62 patients underwent medical thoracoscopy. Tuberculous pleurisy was
      diagnosed in six while uraemic pleuritis was diagnosed in 20 subjects. The
      sensitivity and specificity of pleural fluid ADA, 65 kDa gene PCR, and multiplex
      PCR were 66.7 and 90 per cent, 100 and 50 per cent, and 100 and 100 per cent,
      respectively. Thoracoscopy was associated with five complications in three
      patients. INTERPRETATION & CONCLUSIONS: Uraemia remains the most common cause of
      pleural effusion in CKD even in high TB prevalence country. Multiplex PCR and
      thoracoscopy are useful investigations in the diagnostic work-up of pleural
      effusions complicating CKD while the sensitivity and/or specificity of ADA and 65
      kDa gene PCR is poor.

PMID- 25963489
TI  - Nanoimaging in cardiovascular diseases: Current state of the art.
AB  - Nanotechnology has been integrated into healthcare system in terms of diagnosis
      as well as therapy. The massive impact of imaging nanotechnology has a deeper
      intervention in cardiology i.e. as contrast agents , to target vulnerable plaques
      with site specificity and in a theranostic approach to treat these plaques, stem
      cell delivery in necrotic myocardium, etc. Thus cardiovascular nanoimaging is not
      limited to simple diagnosis but also can help real time tracking during therapy
      as well as surgery. The present review provides a comprehensive description of
      the molecular imaging techniques for cardiovascular diseases with the help of
      nanotechnology and the potential clinical implications of nanotechnology for
      future applications. 

PMID- 25963492
TI  - Evaluation of procalcitonin, C-reactive protein, interleukin-6 & serum amyloid A
      as diagnostic biomarkers of bacterial infection in febrile patients.
AB  - BACKGROUND & OBJECTIVES: Early identification of bacterial infection in patients
      with fever is important for prompt treatment. However, the available parameters
      such as C-reactive protein (CRP) and leukocyte counts are not very specific. This
      study was aimed to assess the diagnostic value of procalcitonin (PCT), CRP,
      interleukin-6 (IL-6) and serum amyloid A (SAA) for bacterial infection in febrile
      patients. METHODS: Serum samples were collected from febrile patients between
      January and December 2012 and processed for blood cultures. PCT, IL-6, CRP and
      SAA levels were measured. The patients were divided into three groups according
      to the final diagnosis: bacteraemia group (group1), bacterial infection with
      negative blood culture (group 2) and non-bacterial infection group (group 3).
      RESULTS: There were significant (P<0.05) difference in the levels of PCT, CRP, IL
      6 and SAA among the three groups. The PCT levels of patients with g0 ram-positive
      bacterial infections were lower than g0 ram-negative bacterial infections (0.53
      vs 2.13, P < 0.01). The best cut-off value to detect bacterial infections was
      0.26 ng/ml for PCT. PCT, CRP, IL-6 and SAA had areas under the curve of 0.804,
      0.693, 0.658 and 0.687, respectively. INTERPRETATION & CONCLUSIONS: Our results
      showed PCT as a valuable marker of bacterial infections in febrile patients. PCT
      was superior to CRP, IL-6 or SAA in the early identification of bacterial
      infection. More prospective and large scale studies are warranted to confirm
      these findings.

PMID- 25963493
TI  - Occurrence of osteoporosis & factors determining bone mineral loss in young
      adults with Graves' disease.
AB  - BACKGROUND & OBJECTIVES: There is a paucity of data with conflicting reports
      regarding the extent and pattern of bone mineral (BM) loss in Graves' disease
      (GD), especially in young adults. Also, interpretation of BM data in Indians is
      limited by use of T-score cut-offs derived from Caucasians. This study was aimed
      to evaluate the occurrence of osteoporosis in active treatment naive patients
      with GD and determine the factors predicting BM loss, using standard T-scores
      from Caucasians and compare with the cut-offs proposed by the Indian Council of
      Medical Research (ICMR) for diagnosing osteoporosis in Indians. METHODS: Patients
      with GD, >20 yr age without any history of use of anti-thyroid drugs, and normal
      controls without fracture history, drugs use or co-morbidities underwent BM
      density (BMD) assessment at lumbar spine, hip and forearm, thyroid function and
      calcium profile assessment. Women with menopause or premature ovarian
      insufficiency and men with androgen deficiency were excluded. RESULTS: p0 atients
      with GD (n=31) had significantly lower BMD at spine (1.01+/-0.10 vs. 1.13+/-0.16
      g/cm 2 ), hip (0.88+/-0.10 vs. 1.04+/-0.19 g/cm 2 ) and forearm (0.46+/-0.04 vs.
      0.59+/-0.09 g/cm 2 ) compared with controls (n=30) (P<0.001). Nine (29%) and six
      (19.3%) patients with GD had osteoporosis as per T-score and ICMR criteria,
      respectively. None of GD patients had osteoporosis at hip or spine as per ICMR
      criteria. Serum T 3 had strongest inverse correlation with BMD at spine, hip and
      femur. Step-wise linear regression analysis after adjusting for age, BMI and
      vitamin D showed T 3 to be the best predictor of reduced BMD at spine, hip and
      forearm, followed by phosphate at forearm and 48 h I 131 uptake for spine BMD in
      GD. INTERPRETATION & CONCLUSIONS: Osteoporosis at hip or spine is not a major
      problem in GD and more commonly involves forearm. Diagnostic criterion developed
      from Caucasians tends to overdiagnose osteoporosis in Indians. T 3 elevation and
      phosphate are important predictors of BMD. Baseline I 131 uptake may have some
      role in predicting BMD.

PMID- 25963494
TI  - Impact on prevalence of intestinal helminth infection in school children
      administered with seven annual rounds of diethyl carbamazine (DEC) with
      albendazole.
AB  - BACKGROUND & OBJECTIVES: One third of the world's population is infected with one
      or more of the most common soil-transmitted helminths (STH). Albendazole (ALB) is
      being administered with diethyl carbamazine (DEC) in filariasis endemic areas to
      eliminate lymphatic filariasis (LF) and helminth infections. In this study, the
      cumulative impact of seven annual rounds of mass drug administrations (MDA) of
      DEC and ALB on STH infection in school children in selected villages in southern
      India was determined. METHODS: During 2001-2010, seven MDAs were implemented by
      the Tamil Nadu s0 tate h0 ealth d0 epartment, India. LF and STH infections were
      monitored in school children from 18 villages of the two treatment arms (viz, DEC
      alone and DEC+ALB). Kato-Katz cellophane quantitative thick smear technique was
      employed to estimate STH infections at three weeks, six months and one year post
      MDA. RESULTS: Prior to treatment, an overall STH prevalence was 60 per cent.
      After each MDA, infection markedly reduced at three weeks post-treatment in both
      the arms. The prevalence increased at six months period, which was maintained up
      to one year. After seven rounds of MDA, the infection reduced from 60.44 to 12.48
      per cent in DEC+ALB arm; while the reduction was negligible in DEC alone arm
      (58.77 to 52.70%). INTERPRETATION & CONCLUSIONS: Seven rounds of MDA with DEC+ALB
      reduced the infection load significantly, and further sustained low level of
      infection for 10 years. However, complete parasite elimination could not be
      achieved. To curtail STH infection in the community, MDA should be regularized
      and environmental sanitation measures need to be improved by effective community
      based campaigns.

PMID- 25963495
TI  - Use of maggot therapy for treating a diabetic foot ulcer colonized by multidrug
      resistant bacteria in Brazil.
AB  - This study reports the efficacy of maggot therapy in the treatment of diabetic
      foot ulcer infected with multidrug resistant microorganisms. A 74 year old female
      patient with diabetes for over 30 years, was treated with maggot therapy using
      larvae of Chrysomya megacephala. The microbiological samples were collected to
      evaluate aetiology of the infection. The therapy done for 43 days resulted in a
      reduction of necrosis and the ulcer's retraction of 0.7 cm [2] in area. Analysis
      of the bacteriological swabs revealed the presence of Escherichia coli,
      Klebsiella pneumoniae and Pseudomonas aeruginosa. Further studies need to be done
      to confirm the role of maggot therapy in wound healing using a large sample and a
      proper study design. 

PMID- 25963496
TI  - Pentacyclic triterpenes combined with ciprofloxacin help to eradicate the biofilm
      formed in vitro by Escherichia coli.
AB  - BACKGROUND & OBJECTIVES: Ciprofloxacin is commonly used in clinical practice for
      the treatment of recurrent urinary tract infections caused by Escherichia coli.
      However, very often these recurrent infections are due to a failure in a complete
      eradication of the microorganisms colonizing the urinary tract, especially in
      catheterized patients. To enhance the bactericidal activity of ciprofloxacin
      against biofilm-forming uropathogenic E. coli (UPECs), we examined its effect in
      combination with two pentacyclic triterpenes - asiatic and ursolic acids.
      METHODS: The anti-biofilm activity of ciprofloxacin and pentacyclic triterpenes -
      asiatic acid (AA) and ursolic acid (UA), as well as their synergistic effect were
      tested on two types of surfaces - polystyrene microtiter plates and silicone
      catheters. It was investigated using the time-killing and biofilm assays.
      RESULTS: a0 nti-biofilm activity of ciprofloxacin was not observed on microtiter
      plates or on the catheters. Ciprofloxacin combined with ursolic acid inhibited
      the biofilm formation on microtitre plates. This mixture, however, did not
      express such a strong activity against the synthesis of biofilm on the surface of
      catheters. Ciprofloxacin combined with asiatic acid had very weak inhibiting
      effect on the synthesis of biofilm mass on microtitre plates as well as on the
      catheters. Despite this, both mixtures - ciprofloxacin and asiatic acid, as well
      as ciprofloxacin and ursolic acid, exhibited strong and significant impact on the
      eradication of mature biofilm (P < 0.05). INTERPRETATION & CONCLUSIONS: Although
      ciprofloxacin is recommended in the treatment of urinary tract infections caused
      by UPECs, but its efficacy is arguable. Subinhibitory concentrations of
      ciprofloxacin did not inhibit the formation of biofilm. Pentacyclic triterpenes
      used in combination with ciprofloxacin enhanced its anti-biofilm effectiveness.
      However, this anti-biofilm activity was found to depend on the type of surface on
      which biofilm was formed.

PMID- 25963497
TI  - Stress, anxiety and depression among medical undergraduate students and their
      socio-demographic correlates.
AB  - BACKGROUND & OBJECTIVES: Presence of psychological morbidity in medical
      undergraduate students has been reported from various countries across the world.
      Indian studies to document this burden are very few. Therefore, the presence of
      depression, anxiety and stress among medical undergraduate students was assessed
      using a previously validated and standardized instrument, Depression Anxiety
      Stress Scale (DASS 42) and the associations with their socio-demographic and
      personal characteristics were identified. METHODS: In a cross-sectional survey, a
      self-administered, pre-designed, pre-tested anonymous questionnaire including
      DASS 42 was used to collect information on basic socio-demographic (age, gender,
      semester) and personal characteristics (alcohol and tobacco use, academic
      performance). All students present on the day of survey were contacted for
      participation after obtaining informed written consent. Scores for each of the
      respondents over each of the sub-scales (Depression, Anxiety and Stress) were
      calculated as per the severity-rating index. RESULTS: More than half of the
      respondents were affected by depression (51.3%), anxiety (66.9%) and stress
      (53%). Morbidity was found to be more in 5 th semester students rather than
      students of 2 nd semester. Females reported higher score as compared to their
      male counterparts. Perception of self assessment in academics was strongly
      associated with the higher score. CONCLUSIONS: A substantial proportion of
      medical undergraduate students was found to be depressed, anxious and stressed
      revealing a neglected area of the students' psychology requiring urgent
      attention. Student counselling services need to be made available and accessible
      to curb this morbidity.

PMID- 25963498
TI  - Association between red blood cell parameters & atrial fibrillation after acute
      myocardial infarction.

PMID- 25963499
TI  - Family history & the risk for adult onset asthma.

PMID- 25963500
TI  - Presence of common mental disorders in patients with diabetes mellitus using a
      two-stage evaluation method.

PMID- 25963501
TI  - Genetic environment of OXA-2 beta-lactamase producing Gram-negative bacilli from
      a tertiary referral hospital.

PMID- 25963502
TI  - Cat's whiskers & corneal verticillata secondary to amiodarone intake.

PMID- 25963503
TI  - A rare case of bilateral nasal block.

PMID- 25963504
TI  - Assessment of surgical portosystemic shunts and associated complications: The
      diagnostic and therapeutic role of radiologists.
AB  - Surgical portosystemic shunting, the formation of a vascular connection between
      the portal and systemic venous circulation, has been used as a treatment to
      reduce portal venous pressure. Although the use of portosystemic shunt surgery in
      the management of portal hypertension has declined during the past decade in
      favour of alternative therapies, and subsequently surgeons and radiologists
      became less familiar with the procedure, it remains a well-established treatment.
      Knowledge of different types of surgical portosystemic shunts, their
      pathophysiology and complications will help radiologists improve communication
      with surgeons and enhance their understanding of the diagnostic and therapeutic
      role of radiology in the assessment and management of these shunts. Optimal
      assessment of the shunt is essential to determine its patency and allow timely
      intervention. Both non-invasive and invasive imaging modalities complement each
      other in the evaluation of surgical portosystemic shunts. Interventional
      radiology plays an important role in the management of complications, such as
      shunt thrombosis and stenosis. This article describes the various types of
      surgical portosystemic shunts, explains the anatomy and pathophysiology of these
      shunts, illustrates the pearls and pitfalls of different imaging modalities in
      the assessment of these shunts and demonstrates the role of radiologists in the
      interventional management of complications. 

PMID- 25963505
TI  - Comparison of applied dose and image quality in staging CT of neuroendocrine
      tumor patients using standard filtered back projection and adaptive statistical
      iterative reconstruction.
AB  - OBJECTIVE: To investigate whether dose reduction via adaptive statistical
      iterative reconstruction (ASIR) affects image quality and diagnostic accuracy in
      neuroendocrine tumor (NET) staging. METHODS: A total of 28 NET patients were
      enrolled in the study. Inclusion criteria were histologically proven NET and
      visible tumor in abdominal computed tomography (CT). In an intraindividual study
      design, the patients underwent a baseline CT (filtered back projection, FBP) and
      follow-up CT (ASIR 40%) using matched scan parameters. Image quality was assessed
      subjectively using a 5-grade scoring system and objectively by determining signal
      to-noise ratio (SNR) and contrast-to-noise ratios (CNRs). Applied volume computed
      tomography dose index (CTDIvol) of each scan was taken from the dose report.
      RESULTS: ASIR 40% significantly reduced CTDIvol (10.17+/-3.06mGy [FBP], 6.34+/
      2.25mGy [ASIR] (p<0.001) by 37.6% and significantly increased CNRs (complete
      tumor-to-liver, 2.76+/-1.87 [FBP], 3.2+/-2.32 [ASIR]) (p<0.05) (complete tumor-to
      muscle, 2.74+/-2.67 [FBP], 4.31+/-4.61 [ASIR]) (p<0.05) compared to FBP.
      Subjective scoring revealed no significant changes for diagnostic confidence
      (5.0+/-0 [FBP], 5.0+/-0 [ASIR]), visibility of suspicious lesion (4.8+/-0.5
      [FBP], 4.8+/-0.5 [ASIR]) and artifacts (5.0+/-0 [FBP], 5.0+/-0 [ASIR]). ASIR 40%
      significantly decreased scores for noise (4.3+/-0.6 [FBP], 4.0+/-0.8 [ASIR])
      (p<0.05), contrast (4.4+/-0.6 [FBP], 4.1+/-0.8 [ASIR]) (p<0.001) and visibility
      of small structures (4.5+/-0.7 [FBP], 4.3+/-0.8 [ASIR]) (p<0.001). CONCLUSION: In
      clinical practice ASIR can be used to reduce radiation dose without sacrificing
      image quality and diagnostic confidence in staging CT of NET patients. This may
      be beneficial for patients with frequent follow-up and significant cumulative
      radiation exposure.

PMID- 25963506
TI  - Changes in anatomical and functional connectivity of Parkinson's disease patients
      according to cognitive status.
AB  - PURPOSE: This study assesses the patterns of structural and functional
      connectivity damage in patients with Parkinson's disease dementia (PDD) compared
      with cognitively unimpaired Parkinson's disease patients (PD-Cu) and healthy
      controls (HC). MATERIALS AND METHODS: Resting state functional magnetic resonance
      imaging (rs-fMRI) and diffusion tensor magnetic resonance imaging (DTI) scans
      were obtained from 30 PD and 21 sex- and age-matched HC. The between-group
      difference in posterior cingulate (PCC) functional connectivity (FC) was
      performed to assess FC dysfunction. Atlas-based spatial statistics of DTI was
      applied to compare White matter (WM) fibers impairment between groups. RESULTS:
      (1) Functional connectivity: (1) PD-Cu compared with HC showed a decreased PCC
      functional connectivity of the right medial temporal lobe (MTL). In addition, PCC
      right MTL connectivity strength of PD was significantly correlated with Montreal
      Cognitive Assessment (MoCA) score. (2) PDD group shows a decreased FC of PCC
      right parahippocampa compared with PD-Cu group; while show a widespread decreased
      PCC FC compared with HC group. (2) Anatomical connectivity: (1) Relative to PD
      Cu, significant lower FA values were found in the left hippocampus in PDD. (2)
      PDD showed higher MD values in a widespread WM regions compared with PD-Cu and
      HC. (3) Positive correlation was observed between MoCA score and FA value of left
      inferior longitudinal and hippocampus, and bilateral superior longitudinal
      fasciculus in PD. CONCLUSIONS: Cognitive decline in PD is associated with FC
      damage of PCC-right MTL and microstructural damage of left hippocampus.
      Nevertheless, combining fMRI and DTI method may provide markers able to
      contribute to the prediction of PDD.

PMID- 25963507
TI  - Thresholds in chemical respiratory sensitisation.
AB  - There is a continuing interest in determining whether it is possible to identify
      thresholds for chemical allergy. Here allergic sensitisation of the respiratory
      tract by chemicals is considered in this context. This is an important
      occupational health problem, being associated with rhinitis and asthma, and in
      addition provides toxicologists and risk assessors with a number of challenges.
      In common with all forms of allergic disease chemical respiratory allergy
      develops in two phases. In the first (induction) phase exposure to a chemical
      allergen (by an appropriate route of exposure) causes immunological priming and
      sensitisation of the respiratory tract. The second (elicitation) phase is
      triggered if a sensitised subject is exposed subsequently to the same chemical
      allergen via inhalation. A secondary immune response will be provoked in the
      respiratory tract resulting in inflammation and the signs and symptoms of a
      respiratory hypersensitivity reaction. In this article attention has focused on
      the identification of threshold values during the acquisition of sensitisation.
      Current mechanistic understanding of allergy is such that it can be assumed that
      the development of sensitisation (and also the elicitation of an allergic
      reaction) is a threshold phenomenon; there will be levels of exposure below which
      sensitisation will not be acquired. That is, all immune responses, including
      allergic sensitisation, have threshold requirement for the availability of
      antigen/allergen, below which a response will fail to develop. The issue
      addressed here is whether there are methods available or clinical/epidemiological
      data that permit the identification of such thresholds. This document reviews
      briefly relevant human studies of occupational asthma, and experimental models
      that have been developed (or are being developed) for the identification and
      characterisation of chemical respiratory allergens. The main conclusion drawn is
      that although there is evidence that the acquisition of sensitisation to chemical
      respiratory allergens is a dose-related phenomenon, and that thresholds exist, it
      is frequently difficult to define accurate numerical values for threshold
      exposure levels. Nevertheless, based on occupational exposure data it may
      sometimes be possible to derive levels of exposure in the workplace, which are
      safe. An additional observation is the lack currently of suitable experimental
      methods for both routine hazard characterisation and the measurement of
      thresholds, and that such methods are still some way off. Given the current
      trajectory of toxicology, and the move towards the use of non-animal in vitro
      and/or in silico) methods, there is a need to consider the development of
      alternative approaches for the identification and characterisation of respiratory
      sensitisation hazards, and for risk assessment. 

PMID- 25963508
TI  - The relationship between selected VDR, HFE and ALAD gene polymorphisms and
      several basic toxicological parameters among persons occupationally exposed to
      lead.
AB  - The aim of this study was to find a relationship between polymorphisms of ALAD
      rs1805313, rs222808, rs1139488, VDR FokI and HFE C282Y and H63D and basic
      toxicological parameters (lead and ZnPP blood concentration) in people
      occupationally exposed to lead. We collected data of 101 workers (age 25-63
      years) directly exposed to lead. The toxicological lab tests included blood lead,
      cadmium and ZnPP concentration measurement and arsenic urine concentration
      measurement. Workers were genotyped for ALAD (rs1805313, rs222808, rs1139488),
      HFE (C282Y, H63D) and VDR (FokI). Individuals with the lead exposure and
      coexisting F allel in the locus Fok-I of VDR gene are suspected of higher zinc
      protoporphyrins concentrations. Workers exposed to the lead with the Y allel in
      the locus C282Y of the HFE gene are predisposed to lower ZnPP levels and
      individuals with coexisting H allel in the locus H63D HFE gene are predisposed to
      lower Pb-B levels. The T allel in the locus rs1805313 of the ALAD gene determines
      lower Pb-B and ZnPP levels in lead-exposed individuals. The heterozigosity of the
      locus rs2228083 of the ALAD gene has a strong predilection to higher Pb-B levels.
      The carriage of the C allel in the locus rs1139488 of the ALAD gene might
      determine higher Pb-B levels and the heterozigosity of the locus rs1139488 of the
      ALAD gene might result in higher ZnPP levels. CONCLUSION: The study revealed
      relationship between VDR, HFE and ALAD genes polymorphism and basic toxicological
      parameters in occupationally exposed workers.

PMID- 25963509
TI  - Therapy. Statins and liver disease: from concern to 'wonder' drugs?
AB  - The benefits of statins go beyond decreasing cholesterol levels; in liver
      disease, statins reduce the risk of progressive liver fibrosis and provide
      protection during infections and ischaemia-reperfusion injury. New evidence shows
      that statins improve response to interferon-based anti-HCV therapy, decrease
      progression to cirrhosis and likelihood of developing hepatocellular carcinoma.

PMID- 25963510
TI  - Hepatitis. New mouse model provides novel insights into hepatitis D virus
      infection and clearance.

PMID- 25963511
TI  - Serrated neoplasia-role in colorectal carcinogenesis and clinical implications.
AB  - Colorectal cancer (CRC) is considered a heterogeneous disease, both regarding
      pathogenesis and clinical behaviour. Four decades ago, the adenoma-carcinoma
      pathway was presented as the main pathway towards CRC, a conclusion that was
      largely based on evidence from observational morphological studies. This concept
      was later substantiated at the genomic level. Over the past decade, evidence has
      been generated for alternative routes in which CRC might develop, in particular
      the serrated neoplasia pathway. Providing indisputable evidence for the
      neoplastic potential of serrated polyps has been difficult. Reasons include the
      absence of reliable longitudinal observations on individual serrated lesions that
      progress to cancer, a shortage of available animal models for serrated lesions
      and challenging culture conditions when generating organoids of serrated lesions
      for in vitro studies. However, a growing body of circumstantial evidence has been
      accumulated, which indicates that >=15% of CRCs might arise through the serrated
      neoplasia pathway. An even larger amount of post-colonoscopy colorectal
      carcinomas (carcinomas occurring within the surveillance interval after a
      complete colonoscopy) have been suggested to originate from serrated polyps. The
      aim of this Review is to assess the current status of the serrated neoplasia
      pathway in CRC and highlight clinical implications. 

PMID- 25963512
TI  - Nutrition. Diet change alters microbiota and might affect cancer risk.

PMID- 25963514
TI  - Using a common commensal bacterium in endangered Takahe as a model to explore
      pathogen dynamics in isolated wildlife populations.
AB  - Predicting and preventing outbreaks of infectious disease in endangered wildlife
      is problematic without an understanding of the biotic and abiotic factors that
      influence pathogen transmission and the genetic variation of microorganisms
      within and between these highly modified host communities. We used a common
      commensal bacterium, Campylobacter spp., in endangered Takahe (Porphyrio
      hochstetteri) populations to develop a model with which to study pathogen
      dynamics in isolated wildlife populations connected through ongoing
      translocations. Takahe are endemic to New Zealand, where their total population
      is approximately 230 individuals. Takahe were translocated from a single remnant
      wild population to multiple offshore and mainland reserves. Several fragmented
      subpopulations are maintained and connected through regular translocations. We
      tested 118 Takahe from 8 locations for fecal Campylobacter spp. via culture and
      DNA extraction and used PCR for species assignment. Factors relating to
      population connectivity and host life history were explored using multivariate
      analytical methods to determine associations between host variables and bacterial
      prevalence. The apparent prevalence of Campylobacter spp. in Takahe was 99%, one
      of the highest reported in avian populations. Variation in prevalence was evident
      among Campylobacter species identified. C. sp. nova 1 (90%) colonized the
      majority of Takahe tested. Prevalence of C. jejuni (38%) and C. coli (24%) was
      different between Takahe subpopulations, and this difference was associated with
      factors related to population management, captivity, rearing environment, and the
      presence of agricultural practices in the location in which birds were sampled.
      Modeling results of Campylobacter spp. in Takahe metapopulations suggest that
      anthropogenic management of endangered species within altered environments may
      have unforeseen effects on microbial exposure, carriage, and disease risk.
      Translocation of wildlife between locations could have unpredictable consequences
      including the spread of novel microbes between isolated populations. 

PMID- 25963513
TI  - Neural reflex pathways in intestinal inflammation: hypotheses to viable therapy.
AB  - Studies in neuroscience and immunology have clarified much of the anatomical and
      cellular basis for bidirectional interactions between the nervous and immune
      systems. As with other organs, intestinal immune responses and the development of
      immunity seems to be modulated by neural reflexes. Sympathetic immune modulation
      and reflexes are well described, and in the past decade the parasympathetic
      efferent vagus nerve has been added to this immune-regulation network. This
      system, designated 'the inflammatory reflex', comprises an afferent arm that
      senses inflammation and an efferent arm that inhibits innate immune responses.
      Intervention in this system as an innovative principle is currently being tested
      in pioneering trials of vagus nerve stimulation using implantable devices to
      treat IBD. Patients benefit from this treatment, but some of the working
      mechanisms remain to be established, for instance, treatment is effective despite
      the vagus nerve not always directly innervating the inflamed tissue. In this
      Review, we will focus on the direct neuronal regulatory mechanisms of immunity in
      the intestine, taking into account current advances regarding the innervation of
      the spleen and lymphoid organs, with a focus on the potential for treatment in
      IBD and other gastrointestinal pathologies. 

PMID- 25963515
TI  - Evidence for two distinct waves of epidermal ionocyte differentiation during
      medaka embryonic development.
AB  - BACKGROUND: The fish epidermis contains specific cells, or ionocytes, that are
      specialized in ion transport and contribute to the osmoregulatory function.
      Besides the zebrafish model, the medaka (Oryzias latipes) has recently emerged as
      an important model for osmoregulation studies because it possesses a particularly
      high adaptability to salinity changes. However, hindering the progress of
      research on embryonic ionocytes is the lack of a comprehensive view of their
      developmental dynamic. RESULTS: Using EdU integrations and the foxi3 and NKA
      markers, we characterized the proliferating progenitors of ionocytes (here called
      ionoblastes) and we quantified them, along with ionocytes, during embryogenesis.
      While progenitors of the vitellin zone promptly differentiate in a synchronous
      manner, progenitors of the lateral zone differentiate progressively and
      asynchronously. Furthermore, we evidenced that nhe3 is expressed in
      differentiated ionocytes of both zones, whereas ecac, ncc, and gcm2 are strictly
      specific of the lateral zone. We also evidenced that the two zones are
      differentially regulated in distilled water and seawater. CONCLUSIONS: Our data
      led us to propose a model timeline, which provides evidence for the expansion of
      two successive and distinct populations of ionocytes. This model opens the way
      for new studies related to epidermal development, plasticity and osmoregulation
      ontogeny.

PMID- 25963516
TI  - MicroRNAs expression patterns in the response of poplar woody root to bending
      stress.
AB  - MAIN CONCLUSION: The paper reports for the first time, in poplar woody root, the
      expression of five mechanically-responsive miRNAs. The observed highly complex
      expression pattern of these miRNAs in the bent root suggest that their expression
      is not only regulated by tension and compression forces highlighting their role
      in several important processes, i.e., lateral root formation, lignin deposition,
      and response to bending stress. Mechanical stress is one of the major abiotic
      stresses significantly affecting plant stability, growth, survival, and
      reproduction. Plants have developed complex machineries to detect mechanical
      perturbations and to improve their anchorage. MicroRNAs (miRNAs), small non
      coding RNAs (18-24 nucleotides long), have been shown to regulate various stress
      responsive genes, proteins and transcription factors, and play a crucial role in
      counteracting adverse conditions. Several mechanical stress-responsive miRNAs
      have been identified in the stem of Populus trichocarpa plants subjected to
      bending stress. However, despite the pivotal role of woody roots in plant
      anchorage, molecular mechanisms regulating poplar woody root responses to
      mechanical stress have still been little investigated. In the present paper, we
      investigate the spatial and temporal expression pattern of five mechanically
      responsive miRNAs in three regions of bent poplar woody taproot and unstressed
      controls by quantitative RT-PCR analysis. Alignment of the cloned and sequenced
      amplified fragments confirmed that their nucleotide sequences are homologous to
      the mechanically-responsive miRNAs identified in bent poplar stem. Computational
      analysis identified putative target genes for each miRNA in the poplar genome.
      Additional miRNA target sites were found in several mechanical stress-related
      factors previously identified in poplar root and a subset of these was further
      analyzed for expression at the mRNA or protein level. Integrating the results of
      miRNAs expression patterns and target gene functions with our previous
      morphological and proteomic data, we concluded that the five miRNAs play crucial
      regulatory roles in reaction woody formation and lateral root development in
      mechanically-stressed poplar taproot.

PMID- 25963517
TI  - Down-regulation of lipoxygenase gene reduces degradation of carotenoids of golden
      rice during storage.
AB  - MAIN CONCLUSION: Down-regulation of lipoxygenase enzyme activity reduces
      degradation of carotenoids of bio-fortified rice seeds which would be an
      effective tool to reduce huge post-harvest and economic losses of bio-fortified
      rice seeds during storage. Bio-fortified provitamin A-enriched rice line (golden
      rice) expressing higher amounts of beta-carotene in the rice endosperm provides
      vitamin A for human health. However, it is already reported that degradation of
      carotenoids during storage is a major problem. The gene responsible for
      degradation of carotenoids during storage has remained largely unexplored till
      now. In our previous study, it has been shown that r9-LOX1 gene is responsible
      for rice seed quality deterioration. In the present study, we attempted to
      investigate if r9-LOX1 gene has any role in degradation of carotenoids in rice
      seeds during storage. To establish our hypothesis, the endogenous lipoxygenase
      (LOX) activity of high-carotenoid golden indica rice seed was silenced by RNAi
      technology using aleurone layer and embryo-specific Oleosin-18 promoter. To check
      the storage stability, LOX enzyme down-regulated high-carotenoid T3 transgenic
      rice seeds were subjected to artificial aging treatment. The results obtained
      from biochemical assays (MDA, ROS) also indicated that after artificial aging,
      the deterioration of LOX-RNAi lines was considerably lower compared to beta
      carotene-enriched transgenic rice which had higher LOX activity in comparison to
      LOX-RNAi lines. Furthermore, it was also observed by HPLC analysis that down
      regulation of LOX gene activity decreases co-oxidation of beta-carotene in LOX
      RNAi golden rice seeds as compared to the beta-carotene-enriched transgenic rice,
      after artificial aging treatment. Therefore, our study substantially establishes
      and verifies that LOX is a key enzyme for catalyzing co-oxidation of beta
      carotene and has a significant role in deterioration of beta-carotene levels in
      the carotenoid-enriched golden rice.

PMID- 25963518
TI  - Contrasting growth responses in lamina and petiole during neighbor detection
      depend on differential auxin responsiveness rather than different auxin levels.
AB  - Foliar shade triggers rapid growth of specific structures that facilitate access
      of the plant to direct sunlight. In leaves of many plant species, this growth
      response is complex because, although shade triggers the elongation of petioles,
      it reduces the growth of the lamina. How the same external cue leads to these
      contrasting growth responses in different parts of the leaf is not understood.
      Using mutant analysis, pharmacological treatment and gene expression analyses, we
      investigated the role of PHYTOCHROME INTERACTING FACTOR7 (PIF7) and the growth
      promoting hormone auxin in these contrasting leaf growth responses. Both petiole
      elongation and lamina growth reduction are dependent on PIF7. The induction of
      auxin production is both necessary and sufficient to induce opposite growth
      responses in petioles vs lamina. However, these contrasting growth responses are
      not caused by different auxin concentrations in the two leaf parts. Our work
      suggests that a transient increase in auxin levels triggers tissue-specific
      growth responses in different leaf parts. We provide evidence suggesting that
      this may be caused by the different sensitivity to auxin in the petiole vs the
      blade and by tissue-specific gene expression.

PMID- 25963519
TI  - Dysfunction in protein clearance by the proteasome: impact on autoinflammatory
      diseases.
AB  - During innate immune responses, proteostasis is greatly impacted by synthesis of
      pathogen proteins as well as by inflammatory tissue damage through radicals or
      other damaging molecules released by phagocytes. An adequate adaptation of
      cellular clearance pathways to the increased burden of damaged proteins is thus
      of fundamental importance for cells and tissues to prevent protein aggregation,
      inclusion body formation, and ultimately cell death. We here review the current
      understanding of the pivotal role of the ubiquitin proteasome system (UPS) in
      this proteostasis network. The proteolytic capacity of the UPS can be adjusted by
      differential gene expression, the incorporation and maturation kinetics of
      alternative active sites, and the attachment of different regulators.
      Dysregulation of this fine-tuning is likely to induce cell death but seen more
      often to promote inflammation as well. The link between proteostasis impairment
      and inflammation may play a crucial role in autoinflammation as well as in age
      related diseases and currently uncharacterized diseases. Recent studies on
      proteasome-associated autoinflammatory syndromes (PRAAS) discovered that IFN
      signaling drives the inflammation caused by reduction of degradation capacity.
      Elucidation of these syndromes will reveal further insights in the understanding
      of inadequate immune responses. Knowledge related to the diversity of this
      degradation system will raise the awareness of potential pitfalls in the
      molecular diagnostics of autoinflammatory syndromes and may help to identify
      novel drug targets. 

PMID- 25963520
TI  - CAPS--pathogenesis, presentation and treatment of an autoinflammatory disease.
AB  - The cryopyrin-associated periodic syndrome (CAPS) is a severity spectrum of rare
      diseases. CAPS comprises the three conditions previously described as familial
      cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal
      onset multisystem inflammatory disorder (NOMID), also known as chronic infantile
      neurologic, cutaneous, and articular (CINCA) syndrome. The clinical phenotype of
      CAPS is characterized by systemic inflammation. General symptoms are fatigue and
      fever. Local manifestations affect multiple tissues such as skin, joints,
      muscles, eyes, and the central nervous system. Distinct clinical features are
      characteristic for each subphenotype. In FCAS, these are cold-induced urticaria
      and fever, in MWS systemic amyloidosis and hearing loss and in NOMID/CINCA
      central nervous system inflammation and bone deformities. CAPS is caused by
      single heterozygous germline or somatic gain of function mutations in the NLRP3
      gene encoding the protein cryopyrin. Cryopyrin nucleates an NLRP3 inflammasome,
      which regulates the activation and cleavage of caspase-1 that cleaves the pro
      inflammatory cytokines, IL-1beta and IL-18. IL-1beta plays the key role in the
      induction of inflammation in CAPS. This has been confirmed by the application of
      IL-1 blocking agents, which lead not only to a rapid and sustained reversal of
      daily symptoms but also to some extent of long-term disease sequelae. To prevent
      CAPS-induced organ damage, early diagnosis and swift initiation of effective
      treatment are mandatory. 

PMID- 25963521
TI  - New monogenic autoinflammatory diseases--a clinical overview.
AB  - Translating pathogenic insights gained from monogenic defects that cause
      autoinflammatory diseases into novel therapies has dramatically improved the
      lives of patients with these syndromes. The last 15 years have focused on the
      central role of IL-1 in driving autoinflammatory phenotypes and on therapies
      blocking IL-1 signaling. Recent discoveries from patients unresponsive to IL-1
      blockade have highlighted other key inflammatory mediators and pathways. New
      genetic discoveries have confirmed unifying mechanisms of autoinflammation,
      including dysregulation of danger sensing, cell stress, and immune-receptor
      signaling. Recent gene discovery in novel diseases has demonstrated new concepts.
      First, several complex clinical syndromes, caused by mutations leading to chronic
      type I interferon (IFN) production present with organ manifestations different
      from IL-1 mediated diseases including cerebral calcifications, myositis, and
      interstitial lung disease and the frequent occurrence of autoantibodies. These
      disorders introduce type I IFN's as inflammatory mediators that cause
      autoinflammatory phenotypes. Second, conditions associated with high IL-18
      production may provide a direct link between autoinflammation and macrophage
      activation syndrome. Third, dysregulation of inflammatory and cell
      differentiation pathways in nonhematopoietic cells, such as aberrant calcium
      signaling and impaired endothelial or keratinocyte development, provide an
      understanding of organ specificity in autoinflammatory disorders. Many of these
      discoveries highlight the intricate interconnections between autoinflammation,
      autoimmunity, immunodeficiency, and lymphoproliferation and suggest ways in which
      we may better diagnose and treat autoinflammatory diseases. 

PMID- 25963522
TI  - Linking canopy leaf area and light environments with tree size distributions to
      explain Amazon forest demography.
AB  - Forest biophysical structure - the arrangement and frequency of leaves and stems 
      emerges from growth, mortality and space filling dynamics, and may also
      influence those dynamics by structuring light environments. To investigate this
      interaction, we developed models that could use LiDAR remote sensing to link leaf
      area profiles with tree size distributions, comparing models which did not
      (metabolic scaling theory) and did allow light to influence this link. We found
      that a light environment-to-structure link was necessary to accurately simulate
      tree size distributions and canopy structure in two contrasting Amazon forests.
      Partitioning leaf area profiles into size-class components, we found that
      demographic rates were related to variation in light absorption, with mortality
      increasing relative to growth in higher light, consistent with a light
      environment feedback to size distributions. Combining LiDAR with models linking
      forest structure and demography offers a high-throughput approach to advance
      theory and investigate climate-relevant tropical forest change. 

PMID- 25963523
TI  - Anti-angiogenic activity of PSA-derived peptides.
AB  - BACKGROUND: PSA is a biomarker for diagnosis and management of prostate cancer.
      PSA is known to have anti-tumorigenic activities, however, the physiological role
      of PSA in prostate tumor progression is not well understood. METHODS: Five
      candidate peptides identified based upon computer modeling of the PSA crystal
      structure and hydrophobicity were synthesized at >95% purity. The peptides in a
      linear form, and a constrained form forced by a di-sulfide bond joining the two
      ends of the peptide, were investigated for anti-angiogenic activity in HUVEC.
      RESULTS: None of the five PSA-mimetic peptides exhibited PSA-like serine protease
      activity. Two of the peptides demonstrated significant anti-angiogenic activity
      in HUVEC based on (i) inhibition of cell migration and invasion; (ii) inhibition
      of tube formation in Matrigel; (iii) anti-angiogenic activity in a sprouting
      assay; and (iv) altered expression of pro- and anti-angiogenic growth factors.
      Constrained PSA-mimetic peptides had greater anti-angiogenic activity than the
      corresponding linearized form. Complexing of PSA with ACT eliminated PSA
      enzymatic activity and reduced anti-angiogenic activity. In contrast, ACT had no
      effect on the anti-angiogenic effects of the linear or constrained PSA-mimetic
      peptides. Modeling of the ACT-PSA complex demonstrated ACT sterically blocks the
      anti-angiogenic activity of the two bioactive peptides. CONCLUSIONS: The
      interaction of a hydrophilic domain on the surface of the PSA molecule with a
      target on the cell membrane of prostate endothelial and epithelial cells was
      responsible for the anti-angiogenic or anti-tumorigenic activity of PSA:
      enzymatic activity was not associated with anti-angiogenic effects. Furthermore,
      since PSA and ACT are both expressed within the human prostate tissue
      microenvironment, the balance of their expression may represent a mechanism for
      endogenous regulation of tissue angiogenesis.

PMID- 25963524
TI  - ARID1A and TERT promoter mutations in dedifferentiated meningioma.
AB  - Unlike patients with World Health Organization (WHO) grade I meningiomas, which
      are considered benign, patients with WHO grade III meningiomas have very high
      mortality rates. The principles underlying tumor progression in meningioma are
      largely unknown, yet a detailed understanding of these mechanisms will be
      required for effective management of patients with these high grade lethal
      tumors. We present a case of an intraventricular meningioma that at first
      presentation displayed remarkable morphologic heterogeneity-composed of distinct
      regions independently fulfilling histopathologic criteria for WHO grade I, II,
      and III designations. The lowest grade regions had classic meningothelial
      features, while the highest grade regions were markedly dedifferentiated. Whereas
      progression in meningiomas is generally observed during recurrence following
      radiation and systemic medical therapies, the current case offers us a snapshot
      of histologic progression and intratumoral heterogeneity in a native pretreatment
      context. Using whole exome sequencing and high resolution array-based comparative
      genomic hybridization, we observed marked genetic heterogeneity between the
      various areas. Notably, in the higher grade regions we found increased aneuploidy
      with progressive loss of heterozygosity, the emergence of mutations in the TERT
      promoter, and compromise of ARID1A. These findings provide new insights into
      intratumoral heterogeneity in the evolution of malignant phenotypes in anaplastic
      meningiomas and potential pathways of malignant progression. 

PMID- 25963525
TI  - Comprehensive evaluation of the effectiveness of gene expression signatures to
      predict complete response to neoadjuvant chemoradiotherapy and guide surgical
      intervention in rectal cancer.
AB  - Neoadjuvant chemoradiotherapy (nCRT) may lead to complete tumor regression in
      rectal cancer patients. Prediction of complete response to nCRT may allow a
      personalized management of rectal cancer and spare patients from unnecessary
      radical total mesorectal excision with or without sphincter preservation. To
      identify a gene expression signature capable of predicting complete pathological
      response (pCR) to nCRT, we performed a gene expression analysis in 25
      pretreatment biopsies from patients who underwent 5FU-based nCRT using RNA-Seq. A
      supervised learning algorithm was used to identify expression signatures capable
      of predicting pCR, and the predictive value of these signatures was validated
      using independent samples. We also evaluated the utility of previously published
      signatures in predicting complete response in our cohort. We identified 27
      differentially expressed genes between patients with pCR and patients with
      incomplete responses to nCRT. Predictive gene signatures using subsets of these
      27 differentially expressed genes peaked at 81.8% accuracy. However, signatures
      with the highest sensitivity showed poor specificity, and vice-versa, when
      applied in an independent set of patients. Testing previously published
      signatures on our cohort also showed poor predictive value. Our results indicate
      that currently available predictive signatures are highly dependent on the sample
      set from which they are derived, and their accuracy is not superior to current
      imaging and clinical parameters used to assess response to nCRT and guide
      surgical intervention. 

PMID- 25963526
TI  - [New cutaneous strategy in sural flap surgery and possibility to adapt this
      technique to other pedicled flaps].
AB  - INTRODUCTION: Therapeutic managements in losses of substance of the lower limb
      using sural flap give an important scar and, sometimes, an impossibility to close
      the flap donor site. That led us to think about an operative procedure that can
      reduce those scars without increasing the risk of necrosis of the cutaneous
      paddle. PATIENTS AND METHOD: We present this operative procedure which underwent
      in the plastic and reconstructive surgery service in our hospital. Classical flap
      procedure with two cutaneous parts was used. The cutaneous laxity was evaluated
      so as to close with one cutaneous part; the other cutaneous part was taken and
      used like a skin graft after the suture of the calf and the formation of a bursa
      on the donor site. The leg was closed with only one cutaneous flap. RESULTS: This
      technique is illustrated by a case report. Results at the 4th month are very
      interesting with an acceptable scar and a good result of the skin graft. However,
      with this technique, we don't decrease the venous risk of this flap. We used this
      technique for an antebrachial flap. CONCLUSION: This technique is an easy and
      reliable technique based on cutaneous laxity and that decreases scarring of this
      very useful flap: the neurocutaneous sural flap. We can have a diminution of the
      number of surgery, a diminution of the scar and good aesthetics results.

PMID- 25963527
TI  - A virtual microscope for academic medical education: the pate project.
AB  - BACKGROUND: Whole-slide imaging (WSI) has become more prominent and continues to
      gain in importance in student teaching. Applications with different scope have
      been developed. Many of these applications have either technical or design
      shortcomings. OBJECTIVE: To design a survey to determine student expectations of
      WSI applications for teaching histological and pathological diagnosis. To develop
      a new WSI application based on the findings of the survey. METHODS: A total of
      216 students were questioned about their experiences and expectations of WSI
      applications, as well as favorable and undesired features. The survey included 14
      multiple choice and two essay questions. Based on the survey, we developed a new
      WSI application called Pate utilizing open source technologies. RESULTS: The
      survey sample included 216 students-62.0% (134) women and 36.1% (78) men. Out of
      216 students, 4 (1.9%) did not disclose their gender. The best-known preexisting
      WSI applications included Mainzer Histo Maps (199/216, 92.1%), Histoweb Tubingen
      (16/216, 7.4%), and Histonet Ulm (8/216, 3.7%). Desired features for the students
      were latitude in the slides (190/216, 88.0%), histological (191/216, 88.4%) and
      pathological (186/216, 86.1%) annotations, points of interest (181/216, 83.8%),
      background information (146/216, 67.6%), and auxiliary informational texts
      (113/216, 52.3%). By contrast, a discussion forum was far less important (9/216,
      4.2%) for the students. CONCLUSIONS: The survey revealed that the students
      appreciate a rich feature set, including WSI functionality, points of interest,
      auxiliary informational texts, and annotations. The development of Pate was
      significantly influenced by the findings of the survey. Although Pate currently
      has some issues with the Zoomify file format, it could be shown that Web
      technologies are capable of providing a high-performance WSI experience, as well
      as a rich feature set.

PMID- 25963528
TI  - Pooled analysis of Swedish case-control studies during 1997-2003 and 2007-2009 on
      meningioma risk associated with the use of mobile and cordless phones.
AB  - A pooled analysis of two case-control studies on meningioma with patients
      diagnosed during 1997-2003 and 2007-2009 was conducted. Both genders were
      included, aged 20-80 and 18-75 years, respectively, at the time of diagnosis.
      Population-based controls, matched according to age and gender, were enrolled.
      Exposure was assessed by questionnaire. In the entire study, cases with all brain
      tumor types were included. The whole reference group was used in the
      unconditional logistic regression analysis on meningioma, with adjustments for
      gender, age, year of diagnosis and socio-economic index (SEI). In total, 1,625
      meningioma cases and 3,530 controls were analyzed. Overall no association with
      use of mobile or cordless phones was found. In the fourth quartile of use (>1,436
      h) somewhat increased risk was found for mobile phones yielding an odds ratio
      (OR)=1.2, 95% confidence intervals (CI)=0.9-1.6 and cordless phones OR=1.7, 95%
      CI=1.3-2.2. Higher risk was calculated in the highest decile (>3,358 h), OR=1.5,
      95% CI=0.99-2.1 and OR=2.0, 95% CI=1.4-2.8, respectively. In addition, the
      longest latency time gave somewhat increased risk for both phone types although
      the result was not statistically significant. There was no association for
      ipsilateral use or anatomical tumor location. The present study showed a somewhat
      increased risk among heavy users of mobile and cordless phones. Since meningioma
      is generally a slow-growing tumor, longer latency period is necessary for
      definitive conclusions.

PMID- 25963529
TI  - Morphological and functional carotid vessel wall properties in relation to
      cerebral white matter lesions in myocardial infarction patients.
AB  - OBJECTIVE: Atherosclerotic large vessel disease is potentially involved in the
      pathogenesis of cerebral small vessel disease related to occurrence of white
      matter lesions (WMLs) in the brain. We aimed to assess morphological and
      functional carotid vessel wall properties in relation to WML using magnetic
      resonance imaging (MRI) in myocardial infarction (MI) patients. MATERIALS AND
      METHODS: A total of 20 MI patients (90 % male, 61 +/- 11 years) underwent carotid
      artery and brain MRI. Carotid vessel wall thickness (VWT) was assessed, by
      detecting lumen and outer wall contours. Carotid pulse wave velocity (PWV), a
      measure of elasticity, was determined using the transit-time method. Patients
      were divided according to the median VWT into two groups. Brain MRI allowed for
      the WML score. RESULTS: Mean VWT was 1.41 +/- 0.29 mm and mean carotid PWV was
      7.0 +/- 2.2 m/s. A significant correlation (Pearson r = 0.45, p = 0.046) between
      VWT and PWV was observed. Furthermore, in the group of high VWT, the median WML
      score was higher as compared with the group with lower VWT (4.0 vs 3.0, p =
      0.035). CONCLUSIONS: Carotid artery morphological and functional alterations are
      correlated in MI patients. Patients with high VWT showed a higher amount of
      periventricular WMLs. These findings support the hypothesis that atherosclerotic
      large vessel disease is potentially involved in the pathogenesis of cerebral
      small vessel disease.

PMID- 25963530
TI  - The number of preproghrelin mRNA expressing cells is increased in mice with
      activity-based anorexia.
AB  - Plasma levels of ghrelin, an orexigenic peptide, are increased during conditions
      of chronic starvation, such as in patients with anorexia nervosa. However, it is
      not known whether such increase can be related to the number of preproghrelin
      mRNA-expressing cells in the stomach, and if chronic starvation may activate a
      tentative central ghrelin production. In this work, in situ hybridization
      technique was used to analyze the presence and number of preproghrelin mRNA
      expressing cells in the stomach and the hypothalamus of mice with activity-based
      anorexia (ABA) induced by the combination of running wheel activity with
      progressive, during 10 days, feeding-time restriction (FTR) and compared with
      sedentary FTR, ABA pair-fed (PF) and ad libitum-fed control mice. All food
      restricted mice lost more than 20% of body weight. Body weight loss was similar
      in ABA and PF mice, but it was more pronounced than in FTR mice. Food intake was
      also lower in ABA than in FTR mice. Preproghrelin mRNA-expressing cells in the
      stomach were increased proportionally to the body weight loss in all food
      restricted groups with the highest number in ABA mice. No preproghrelin mRNA
      producing cells were detectable in the hypothalamus of either control or food
      restricted mice. Thus, the increased number of gastric preproghrelin mRNA
      producing cells during chronic starvation proportionally to the body weight loss
      and reduced food intake may underlie increased plasma ghrelin. Hyperactivity
      induced anorexia appears to further increase the number of preproghrelin mRNA
      producing cells in the stomach. No evidence was found for ghrelin expression in
      the hypothalamus, not even in any of the present experimental models. 

PMID- 25963531
TI  - Chronic stress associated with hypercaloric diet changes the hippocampal BDNF
      levels in male Wistar rats.
AB  - Chronic stress, whether associated with obesity or not, leads to different
      neuroendocrine and psychological changes. Obesity or being overweight has become
      one of the most serious worldwide public health problems. Additionally, it is
      related to a substantial increase in daily energy intake, which results in
      substituting nutritionally adequate meals for snacks. This metabolic disorder can
      lead to morbidity, mortality, and reduced quality of life. On the other hand,
      brain-derived neurotrophic factor (BDNF) is widely expressed in all brain
      regions, particularly in the hypothalamus, where it has important effects on
      neuroprotection, synaptic plasticity, mammalian food intake-behavior, and energy
      metabolism. BDNF is involved in many activities modulated by the hypothalamic
      pituitary-adrenal (HPA) axis. Therefore, this study aims to evaluate the effect
      of obesity associated with chronic stress on the BDNF central levels of rats.
      Obesity was controlled by analyzing the animals' caloric intake and changes in
      body weight. As a stress parameter, we analyzed the relative adrenal gland
      weight. We found that exposure to chronic restraint stress during 12 weeks
      increases the adrenal gland weight, decreases the BDNF levels in the hippocampus
      and is associated with a decrease in the calorie and sucrose intake,
      characterizing anhedonia. These effects can be related stress, a phenomenon that
      induces depression-like behavior. On the other hand, the rats that received the
      hypercaloric diet had an increase in calorie intake and became obese, which was
      associated with a decrease in hypothalamus BDNF levels. 

PMID- 25963532
TI  - Comment on: Aesthetic and Functional Outcomes of Neovaginoplasty Using Penile
      Skin in Male-to-Female Transsexuals.

PMID- 25963533
TI  - TCF4 Mediates the Maintenance of Neuropathic Pain Through Wnt/beta-Catenin
      Signaling Following Peripheral Nerve Injury in Rats.
AB  - Neuropathic pain is elicited after a serious disorder of the nervous system and
      is along with the neural damage. It is usually chronic and challenging to treat.
      Transcription factor 4 (TCF4) is a key transcription factor of Wnt signaling
      system. Recent studies have shown that TCF4 interacts with beta-catenin in the
      Wnt signaling pathway and coactivates downstream target genes in diverse systems.
      However, it is not well elucidated in the pathogenesis of neuropathic pain. In
      the present study, we investigated the role of TCF4 in the maintenance of
      neuropathic pain after chronic constriction injury (CCI) in rats. CCI induced
      persistent TCF4 upregulation in the dorsal root ganglion and spinal cord.
      Interestingly, TCF4 was mainly colocalized with neurons in the injured dorsal
      root ganglion and spinal cord on CCI day 7. Moreover, the expression patterns of
      beta-catenin and glycogen synthase kinase-3beta (GSK-3beta) were parallel with
      that of TCF4 in vivo studies. Intrathecal injection of Wnt/beta-catenin pathway
      inhibitor IWR-1-endo and TCF4 small interfering RNA (siRNA) significantly
      attenuated CCI-induced mechanical allodynia and heat hyperalgesia. The results
      suggest that TCF4 in the dorsal root ganglion and spinal cord is involved in the
      maintenance of CCI-induced neuropathic pain. Targeting TCF4 or Wnt/beta-catenin
      signaling may be a potential treatment for chronic neuropathic pain. 

PMID- 25963534
TI  - Treatment of infants with epilepsy: Common practices around the world.
AB  - OBJECTIVES: High quality data to guide recommendations for infants with epilepsy
      are lacking. This study aimed to develop an understanding of common practice and
      regional variations in the treatment interventions of infants with epilepsy, and
      also to identify areas for further study and to highlight where common practice
      occurs without sound evidence. METHOD: A survey addressed clinical treatment
      practice for infants with epilepsy. Alternative interventions were included.
      RESULTS: The survey found that most regions had similar practice for first-line
      interventions, except for North America, where more levetiracetam was prescribed.
      There was a preference for valproate as first-line therapy for generalized
      seizures, myoclonic seizures, and Dravet syndrome; only Oceania differed for
      generalized and myoclonic seizures. Phenobarbital was used for generalized and
      focal seizures in resource-poor and resource-equipped regions. Carbamazepine and
      oxcarbazepine were the preferred agents for focal seizures from all regions
      except North America, which uses more levetiracetam. For second- and third-line
      interventions, the range of choices was diverse, often with little correlation
      across regions. The ketogenic diet, vagus nerve stimulation, and epilepsy surgery
      were considered viable choices in most settings, but usually only once seizures
      were considered medically refractory. The survey highlighted the marked
      discrepancy in Africa, the one region that consistently confirmed a lack of
      access to these alternative interventions and to the newer antiepileptic drugs.
      SIGNIFICANCE: More randomized controlled trials in infants with seizures are
      needed to permit useful recommendations. The survey identified widespread use of
      levetiracetam in North America, which may be the result of effective marketing or
      based on good clinical practice. The widespread use of valproate may have safety
      implications. The lack of access to care in the African region highlighted the
      need for more sustained resources. Although the survey was not evidence based,
      the findings could be useful to support additional well-designed studies.

PMID- 25963535
TI  - Susceptibility to and transmission of H5N1 and H7N1 highly pathogenic avian
      influenza viruses in bank voles (Myodes glareolus).
AB  - The study of influenza type A (IA) infections in wild mammals populations is a
      critical gap in our knowledge of how IA viruses evolve in novel hosts that could
      be in close contact with avian reservoir species and other wild animals. The aim
      of this study was to evaluate the susceptibility to infection, the nasal shedding
      and the transmissibility of the H7N1 and H5N1 highly pathogenic avian influenza
      (HPAI) viruses in the bank vole (Myodes glareolus), a wild rodent common
      throughout Europe and Asia. Two out of 24 H5N1-infected voles displayed evident
      respiratory distress, while H7N1-infected voles remained asymptomatic. Viable
      virus was isolated from nasal washes collected from animals infected with both
      HPAI viruses, and extra-pulmonary infection was confirmed in both experimental
      groups. Histopathological lesions were evident in the respiratory tract of
      infected animals, although immunohistochemistry positivity was only detected in
      lungs and trachea of two H7N1-infected voles. Both HPAI viruses were transmitted
      by direct contact, and seroconversion was confirmed in 50% and 12.5% of the
      asymptomatic sentinels in the H7N1 and H5N1 groups, respectively. Interestingly,
      viable virus was isolated from lungs and nasal washes collected from contact
      sentinels of both groups. The present study demonstrated that two non-rodent
      adapted HPAI viruses caused asymptomatic infection in bank voles, which shed high
      amounts of the viruses and were able to infect contact voles. Further
      investigations are needed to determine whether bank voles could be involved as
      silent hosts in the transmission of HPAI viruses to other mammals and domestic
      poultry. 

PMID- 25963536
TI  - Intrinsic disorder of human Yin Yang 1 protein.
AB  - YY1 (Yin Yang 1) is a zinc finger protein with an essential role in various
      biological functions via DNA- and protein-protein interactions with numerous
      partners. YY1 is involved in the regulation of a broad spectrum of cellular
      processes such as embryogenesis, proliferation, tumorigenesis, and snRNA
      transcription. The more than 100 reported targets of the YY1 protein suggest that
      it contains intrinsically disordered regions that are involved in such diverse
      interactions. Here, we present a study of the structural properties of human YY1
      using several biochemical and biophysical techniques (fluorescence, circular
      dichroism, gel filtration chromatography, proteolytic susceptibility) together
      with various bioinformatics approaches. To facilitate our exploration of the YY1
      structure, the full-length protein as well as an N-terminal fragment (residues 1
      295) and the C-terminal DNA binding domain were used. We found the N-terminus to
      be a non-compact fragment of YY1 with little residual secondary structure and
      lacking a well-defined tertiary structure. The results of our study indicate that
      YY1 belongs to the family of intrinsically disordered proteins (IDPs), which
      exist natively in a partially unfolded conformation.

PMID- 25963537
TI  - ZEB1 promotes epithelial-mesenchymal transition in cervical cancer metastasis.
AB  - OBJECTIVE: To investigate role of Zinc finger E-box binding homeobox 1 (ZEB1) in
      cervical cancer tissue (squamous cell carcinoma, SCC). DESIGN: Exploratory study.
      SETTING: University hospital. PATIENT(S): Sixty patients with SCC, including
      stage CINIII (n = 10), IB1 (n = 10), IB2 (n = 10), IIA1 (n = 10), IIA2 (n = 10),
      and IIB (n = 10) were studied. INTERVENTION(S): Caski cells were transfected with
      recombinant shZEB1 lentivirus or shCtrl lentivirus to generate stable ZEB1
      knockdown Caski cells. MAIN OUTCOME MEASURE(S): ZEB1 expression was analyzed by
      quantitative real-time polymerase chain reaction and immunohistochemistry in
      cervical cancer tissues. ZEB1 expression in Caski cells was down-regulated by
      short-hairpin RNA (shRNA) interference, and changes in ZEB1 expression
      corresponded with changes in the proliferation and migratory ability of Caski
      cells. RESULT(S): Quantitative real-time polymerase chain reaction and
      immunohistochemistry results revealed that ZEB1 expression and the ratio of
      Vimentin to E-cadherin were high in 27 of 50 SCC patients and correlated with
      advanced International Federation of Gynecology and Obstetrics stage, tumor size
      >4 cm, and parametrial invasion. However, the expression of ZEB1 in cervical
      cancer tissue was independent of age and SCC antigen level. Transfection of ZEB1
      shRNA in Caski cells significantly decreased the messenger RNA and protein
      expression of ZEB1, parallel with increased expression of the epithelial marker E
      cadherin and decreased expression of the mesenchymal marker Vimentin.
      Furthermore, the proliferation and migratory ability of Caski cells were
      significantly lower in the transfected group than in the nontransfected control
      group. CONCLUSION(S): Down-regulation of ZEB1 expression may protect the invasive
      front of the tumors from converting to a mesenchymal phenotype by reducing the
      proliferation and motility of cervical cancer cells, suggesting that ZEB1 might
      be a potential therapeutic target for SCC.

PMID- 25963539
TI  - A case of eosinophilic disorder that evolved in acute lymphoblastyc leukemia.

PMID- 25963540
TI  - FoxO1 integrates direct and indirect effects of insulin on hepatic glucose
      production and glucose utilization.
AB  - FoxO proteins are major targets of insulin action. To better define the role of
      FoxO1 in mediating insulin effects in the liver, we generated liver-specific
      insulin receptor knockout (LIRKO) and IR/FoxO1 double knockout (LIRFKO) mice.
      Here we show that LIRKO mice are severely insulin resistant based on glucose,
      insulin and C-peptide levels, and glucose and insulin tolerance tests, and
      genetic deletion of hepatic FoxO1 reverses these effects. (13)C-glucose and
      insulin clamp studies indicate that regulation of both hepatic glucose production
      (HGP) and glucose utilization is impaired in LIRKO mice, and these defects are
      also restored in LIRFKO mice corresponding to changes in gene expression. We
      conclude that (1) inhibition of FoxO1 is critical for both direct (hepatic) and
      indirect effects of insulin on HGP and utilization, and (2) extrahepatic effects
      of insulin are sufficient to maintain normal whole-body and hepatic glucose
      metabolism when liver FoxO1 activity is disrupted. 

PMID- 25963541
TI  - Multiplug paravalvular leak closure using Amplatzer Vascular Plugs III: A
      prospective registry.
AB  - BACKGROUND: Transcatheter paravalvular leak closure (TPVLC) offers a viable
      alternative to reoperation but optimal technical strategy is still to be defined.
      We present a prospective TPVLC registry in which safety and efficacy of multi
      plug, single-stage approach were assessed. METHODS: Patients with heart failure
      (HF) symptoms caused by PVL were qualified for TPVLC by Heart Team. Ante- or
      retrograde access was employed for mitral while retrograde only for aortic PVLs.
      Two to 4 AVP 3 devices were simultaneously implanted into each PVL. Endpoints
      were defined according to VARC-2. RESULTS: From 64 referred patients 49, with
      either mechanical valves (n = 30) or stented bioprostheses, were eligible for
      TPVLC. PVL location was mitral (n = 29) or aortic (n = 20). In aortic group acute
      procedural success (APS) ratio was 100% and no MACCEs occurred. In mitral group,
      first-attempt TPVLC was successful in 22 cases (4/4 in transapical and 18/25 in
      transseptal access). Second-attempt transapical procedure followed transseptal
      failure in 5 patients. Mitral TPVLC ultimately proved efficient in 89.7% with
      76.5% APS. Cumulatively, TPVLC was accomplished in 46 subjects (93.9%) with 78%
      APS. When successful, it led to a significant decrease of NT-proBNP concentration
      and HF symptoms regression. Periprocedural safety endpoints were met in three
      patients and included non-disabling stroke, and two access site-related
      complications. In device failure group two patients died (end-stage HF) and two
      others were rehospitalized. CONCLUSION: TPVLC with simultaneous deployment of
      multiple AVP III occluders is feasible with high device success rate and no
      significant periprocedural complications. The clinical benefits of reduction of
      HF symptoms and hemolysis are evident after 30 days and persist up to 1 year
      without recurrence of PVL.

PMID- 25963542
TI  - Ornithodoros faccinii n. sp. (Acari: Ixodida: Argasidae) parasitizing the frog
      Thoropa miliaris (Amphibia: Anura: Cycloramphidae) in Brazil.
AB  - BACKGROUND: Most argasid ticks from the Neotropical region are parasites of
      mammals and birds, with a few records from reptiles. Many species of the genus
      Ornithodoros are known only through larval descriptions, and their chaetotaxy and
      morphological characteristics have been used to separate the taxa. In the present
      study, we describe the larva and the nymph of first instar of a new species of
      the genus Ornithodoros that was collected from frogs of the species Thoropa
      miliaris. METHODS: Larvae of Ornithodoros were collected from frogs of the
      species T. miliaris at waterfalls in the state of Rio de Janeiro, southeastern
      Brazil. The larval and nymphal description was based on optical and scanning
      electron microscopy. Molecular analysis using the argasid 16S rRNA sequences
      available in GenBank was also conducted. RESULTS: Ornithodoros faccinii sp. n. is
      closely related to Ornithodoros clarki Jones & Clifford, Ornithodoros marinkellei
      Kohls, Clifford & Jones, Ornithodoros capensis Neumann and Ornithodoros sawaii
      Kitaoka & Susuki. However, the larval morphology of the new species is unique.
      The mitochondrial 16S rDNA partial sequence of O. faccinii generated in the
      present study was deposited in GenBank under the number KP861242. CONCLUSIONS:
      The larvae collected from Thoropa miliaris are a new species, Ornithodoros
      faccinii n. sp. This is the first report of argasid ticks on frogs in Brazil, the
      second on frogs and the third on Amphibia in the Neotropical region.

PMID- 25963543
TI  - Identification of anti-inflammatory fractions of Geranium wilfordii using tumor
      necrosis factor-alpha as a drug target on Herbochip(r) - an array-based high
      throughput screening platform.
AB  - BACKGROUND: Geranium wilfordii is one of the major species used as Herba Geranii
      (lao-guan-cao) in China, it is commonly used solely or in polyherbal formulations
      for treatment of joint pain resulted from rheumatoid arthritis (RA) and gout.
      This herb is used to validate a target-based drug screening platform called
      Herbochip(r) and evaluate anti-inflammatory effects of Geranium wilfordii
      ethanolic extract (GWE) using tumor necrosis factor-alpha (TNF-alpha) as a drug
      target together with subsequent in vitro and in vivo assays. METHODS: A
      microarray-based drug screening platform was constructed by arraying HPLC
      fractions of herbal extracts onto a surface-activated polystyrene slide
      (Herbochip(r)). Using TNF-alpha as a molecular probe, fractions of 82 selected
      herbal extracts, including GWE, were then screened to identify plant extracts
      containing TNF-alpha-binding agents. Cytotoxicity of GWE and modulatory effects
      of GWE on TNF-alpha expression were evaluated by cell-based assays using TNF
      alpha sensitive murine fibrosarcoma L929 cells as an in vitro model. RESULTS: The
      in vivo anti-inflammatory effects of GWE were further assessed by animal models
      including carrageenan-induced hind paw edema in rats and xylene-induced ear edema
      in mice, in comparison with aspirin. The hybridization data obtained by
      Herbochip(r) analysis showed unambiguous signals which confirmed TNF-alpha
      binding activity in 46 herbal extracts including GWE. In L929 cells GWE showed
      significant inhibitory effect on TNF-alpha expression with negligible
      cytotoxicity. GWE also significantly inhibited formation of carrageenan-induced
      hind paw edema and xylene-induced ear edema in animal models, indicating that it
      indeed possessed anti-inflammatory activity. CONCLUSION: We have thus validated
      effectiveness of the Herbochip(r) drug screening platform using TNF-alpha as a
      molecular target. Subsequent experiments on GWE lead us to conclude that the anti
      RA activity of GWE can be attributed to inhibitory effect of GWE on the key
      inflammatory factor, TNF-alpha. Our results contribute towards validation of the
      traditional use of GWE in the treatment of RA and other inflammatory joint
      disorders.

PMID- 25963544
TI  - A Multiplexed NMR-Reporter Approach to Measure Cellular Kinase and Phosphatase
      Activities in Real-Time.
AB  - Cell signaling is governed by dynamic changes in kinase and phosphatase
      activities, which are difficult to assess with discontinuous readout methods.
      Here, we introduce an NMR-based reporter approach to directly identify active
      kinases and phosphatases in complex physiological environments such as cell
      lysates and to measure their individual activities in a semicontinuous fashion.
      Multiplexed NMR profiling of reporter phosphorylation states provides unique
      advantages for kinase inhibitor studies and reveals reversible modulations of
      cellular enzyme activities under different metabolic conditions. 

PMID- 25963546
TI  - Hypertension Suppression, Not a Cumulative Thrust of Quantitative Trait Loci,
      Predisposes Blood Pressure Homeostasis to Normotension.
AB  - BACKGROUND: Genetics of high blood pressure (BP) has revealed causes of
      hypertension. The cause of normotension, however, is poorly understood. Inbred
      Lewis rats sustain normotension despite a genetic push in altering BP. It was
      unknown whether this rigid resistance to BP changes is because of an insufficient
      hypertensive impact from limited alleles of quantitative trait loci (QTLs) or
      because of an existence of a master control superseding the combined strength of
      hypertensive QTL alleles. METHODS AND RESULTS: Currently, BP-elevating QTL
      alleles from hypertensive Dahl salt-sensitive rats (DSS) replaced those of Lewis
      on chromosomes 7, 8, 10, and 17 on the Lewis background. These hypertensive QTL
      alleles were then merged to systematically achieve multiple combinations. Results
      showed that there was no quantitative correlation between BP variations and the
      number of hypertensive QTL alleles, and that BP was only slightly elevated from a
      combined force of normotensive alleles from 7 QTLs. Thus, a genetic factor aside
      from the known QTLs seemed to be at play in preserving normotension and act as a
      hypertension suppressor. A follow-up study using consecutive backcrosses from
      Dahl salt-sensitive rats and Lewis identified a chromosome segment where a
      hypertension suppressor might reside. CONCLUSIONS: Our results provide the first
      evidence that normotension is not enacted via a numeric advantage of BP-lowering
      QTL alleles, and instead can be achieved by a particular genetic component
      actively suppressing hypertensive QTL alleles. The identification of this
      hypertension suppressor could result in formulating unique diagnostic and
      therapeutic targets, and above all, preventive measures against essential
      hypertension.

PMID- 25963545
TI  - Haploinsufficiency of the NOTCH1 Receptor as a Cause of Adams-Oliver Syndrome
      With Variable Cardiac Anomalies.
AB  - BACKGROUND: Adams-Oliver syndrome (AOS) is a rare disorder characterized by
      congenital limb defects and scalp cutis aplasia. In a proportion of cases,
      notable cardiac involvement is also apparent. Despite recent advances in the
      understanding of the genetic basis of AOS, for the majority of affected subjects,
      the underlying molecular defect remains unresolved. This study aimed to identify
      novel genetic determinants of AOS. METHODS AND RESULTS: Whole-exome sequencing
      was performed for 12 probands, each with a clinical diagnosis of AOS. Analyses
      led to the identification of novel heterozygous truncating NOTCH1 mutations
      (c.1649dupA and c.6049_6050delTC) in 2 kindreds in which AOS was segregating as
      an autosomal dominant trait. Screening a cohort of 52 unrelated AOS subjects, we
      detected 8 additional unique NOTCH1 mutations, including 3 de novo amino acid
      substitutions, all within the ligand-binding domain. Congenital heart anomalies
      were noted in 47% (8/17) of NOTCH1-positive probands and affected family members.
      In leukocyte-derived RNA from subjects harboring NOTCH1 extracellular domain
      mutations, we observed significant reduction of NOTCH1 expression, suggesting
      instability and degradation of mutant mRNA transcripts by the cellular machinery.
      Transient transfection of mutagenized NOTCH1 missense constructs also revealed
      significant reduction in gene expression. Mutant NOTCH1 expression was associated
      with downregulation of the Notch target genes HEY1 and HES1, indicating that
      NOTCH1-related AOS arises through dysregulation of the Notch signaling pathway.
      CONCLUSIONS: These findings highlight a key role for NOTCH1 across a range of
      developmental anomalies that include cardiac defects and implicate NOTCH1
      haploinsufficiency as a likely molecular mechanism for this group of disorders.

PMID- 25963548
TI  - The Innovation Imperative: Scaling Freestanding Birth Centers,
      CenteringPregnancy, and Midwifery-Led Maternity Health Homes.

PMID- 25963547
TI  - Genetic and clinical factors associated with obesity among adult survivors of
      childhood cancer: A report from the St. Jude Lifetime Cohort.
AB  - BACKGROUND: The objective of this study was to identify treatment and genetic
      factors associated with obesity among childhood cancer survivors. METHODS:
      Participants included 1996 survivors who previously received treatment for cancer
      at St. Jude Children's Research Hospital and who survived >=10 years from
      diagnosis (median age at diagnosis, 7.2 years; median age at follow-up, 32.4
      years). Obesity was defined as a body mass index >=30 kg/m(2) . The factors
      associated with adult obesity were identified by subgroup-specific (cranial
      radiation [CRT] exposure status) multivariable logistic regression. Single
      nucleotide polymorphisms (SNPs) associated with obesity were identified by
      subgroup-specific, exploratory, genome-wide association analyses using a 2-stage
      resampling approach with a type I error rate of 5 * 10(-6) . RESULTS: Forty-seven
      percent of survivors who received CRT and 29.4% of those who did not receive CRT
      were obese at evaluation. In multivariable analyses, abdominal/pelvic radiation
      exposure was associated with decreased prevalence of obesity among survivors
      regardless of CRT status (P < .0001). The odds of obesity were increased among
      survivors who received CRT who had also received glucocorticoids (P = .014) or
      who were younger at diagnosis (P = .013). Among the survivors who had received
      CRT, 166 SNPs were associated with obesity. The strongest association was
      observed with reference SNP rs35669975 (P = 3.3 * 10(-8) ) on segment 33.3 of the
      long arm of chromosome 13 (13q33.3), approximately 30 kb downstream of FAM155A
      (family with sequence similarity 155, member A). SNPs within the glycine receptor
      alpha3 (GLRA3) gene and near the sex-determining region Y box 11 (SOX11) and
      cadherin 18 type 2 (CDH18) genes also were identified. These genes have been
      implicated in neural growth, repair, and connectivity. CONCLUSIONS: Obesity in
      childhood cancer survivors remains associated with previous exposure to CRT and
      glucocorticoids. Genetic variants related to neural connectivity may modify the
      risk of obesity among survivors who receive CRT. Validation of these findings in
      independent cohorts is required.

PMID- 25963549
TI  - Polyamine derivatives of betulinic acid and beta-sitosterol: A comparative
      investigation.
AB  - beta-Sitosterol and betulinic acid were used in designing their conjugates with
      selected polyamines bearing either an amide bond, or an ester and an amide bond
      simultaneously in the target molecule. The synthesized compounds were subjected
      to basic cytotoxic and antimicrobial tests. The synthetic protocol is described
      separately for each of the three series of the target amides, because each series
      of compounds required a different synthetic approach. The cytotoxicity was tested
      on cells derived from human T-lymphoblastic leukemia, breast adenocarcinoma and
      cervical cancer, and compared with the tests on normal human fibroblasts. Most of
      the target compounds (5a-5c, 11a-11c and 16a-16c) showed medium to high
      cytotoxicity (0.7-7.8 MUM), however, in some cases the compounds showed high
      cytotoxicity even toward normal human fibroblasts (11a-11c). Two compounds of
      this series (11c and 16c) also displayed antimicrobial activity with high and
      selective microbe specificity. The compound 11c was potent against Escherichia
      coli (minimal inhibition concentration (MIC) 6.25 MUg mL(-1), i.e. 9.75 nM mL(
      1)) and Staphylococcus aureus (MIC 12.5 MUg mL(-1), i.e. 19.5 nM mL(-1)), and
      showed medium activity against Pseudomonas aeruginosa. The compound 16c was
      highly active against Enterococcus faecalis and S. aureus (both, MIC 3.125 MUg
      mL(-1), i.e. 4.22 nM mL(-1)), both Gram-positive bacteria, however showed only
      weak activity against E. coli and no activity against P. aeruginosa, both Gram
      negative bacteria, which indicates possible microbe specificity of 16c. Comparing
      beta-sitosterol-based series (5a-5c) and betulinic acid series (11a-11c and 16a
      16c) of the target compounds, the latter one gave more promising structures. The
      compounds 11c and 16c showed effects which may be described as multifarious
      activity (pleiotropic effects).

PMID- 25963550
TI  - Effects of Seasonality and Dispersal on the Ciliate Community Inhabiting
      Bromeliad Phytotelmata in Riparian Vegetation of a Large Tropical River.
AB  - This study evaluated the influence of rainfall amount on the abundance, species
      richness, and species occurrence and abundance distribution of the ciliate
      community associated with the bromeliad Aechmea distichantha. The plants were
      collected from a rock wall of about 10-km long at the left bank of Parana River.
      We assessed the effects of both spatial and temporal variables on the community
      attributes, as well as whether plants geographically closer have a similar
      abundance distribution and species composition. The ciliate community was
      substantially distinct between both hydrological periods, with greater values of
      species richness and abundance in the rainy period. No spatial structuring
      (differences in the species occurrence and abundance distribution among strata)
      or geographical similarity (similarity in ciliate species composition among the
      plants) was found. Multiple regression analysis showed a positive relationship
      only between the ciliate abundances and water volumes for both periods. Although
      few of the formulated predictions were confirmed, our study provides valuable
      information on the ecological aspects of the ciliate community inhabiting
      bromeliad phytotelmata. 

PMID- 25963551
TI  - The discovery of methionine sulfoxide reductase enzymes: An historical account
      and future perspectives.
AB  - L-Methionine (L-Met) is the only sulphur-containing proteinogenic amino acid
      together with cysteine. Its importance is highlighted by it being the initiator
      amino acid for protein synthesis in all known living organisms. L-Met, free or
      inserted into proteins, is sensitive to oxidation of its sulfide moiety, with
      formation of L-Met sulfoxide. The sulfoxide could not be inserted into proteins,
      and the oxidation of L-Met in proteins often leads to the loss of biological
      activity of the affected molecule. Key discoveries revealed the existence, in
      rats, of a metabolic pathway for the reduction of free L-Met sulfoxide and,
      later, in Escherichia coli, of the enzymatic reduction of L-Met sulfoxide
      inserted in proteins. Upon oxidation, the sulphur atom becomes a new stereogenic
      center, and two stable diastereoisomers of L-Met sulfoxide exist. A fundamental
      discovery revealed the existence of two unrelated families of enzymes, MsrA and
      MsrB, whose members display opposite stereospecificity of reduction for the two
      sulfoxides. The importance of Msrs is additionally emphasized by the discovery
      that one of the only 25 selenoproteins expressed in humans is a Msr. The
      milestones on the road that led to the discovery and characterization of this
      group of antioxidant enzymes are recounted in this review.

PMID- 25963552
TI  - Impact of bacterial and viral challenge on multidrug resistance in first- and
      third-trimester human placenta.
AB  - The ABC transporters P-glycoprotein (P-gp, official gene symbol ABCB1) and breast
      cancer resistance protein (BCRP, official gene symbol ABCG2) protect the
      conceptus from exposure to toxins and xenobiotics present in the maternal
      circulation. Viral or bacterial challenges alter expression of placental
      multidrug transporters in rodents. We hypothesized that exposure to
      lipopolysaccharide (LPS, bacterial antigen) and polyinosinic-polycytidylic acid
      (poly(I:C), viral antigen) would decrease P-gp and BCRP in the human placenta.
      Placental explants from first and third trimesters were challenged with 0.1 to 10
      MUg/mL LPS or 1 to 50 MUg/mL poly(I:C) for 4 or 24 hours; mRNA levels, protein
      expression, and localization were assessed by quantitative real-time PCR, Western
      blot analysis, and immunohistochemistry, respectively. Toll-like receptor (TLR)-3
      and TLR-4 mRNA expression increased from the first to third trimester (P < 0.01),
      and the receptors localized to cytotrophoblasts in the first trimester and to
      syncytiotrophoblasts in the third trimester. LPS exposure in first-trimester
      explants decreased (P < 0.001) ABCB1 and ABCG2 mRNA and protein levels. In
      contrast, poly(I:C) decreased (P < 0.05) ABCB1, TLR-3, and TLR-4 mRNA levels in
      the third trimester but not first trimester. LPS and poly(I:C) treatments
      increased (P < 0.01) IL-8 and chemokine ligand 2. Results suggest that bacterial
      infections likely alter exposure of the conceptus to toxins and drugs during
      early pregnancy, whereas viral infections may disrupt fetal protection in later
      stages of pregnancy.

PMID- 25963553
TI  - Insights into end-organ injury in HIV infection: dynamics of monocyte trafficking
      to the brain in SIV encephalitis.
AB  - This commentary highlights the article by Nowlin et al, which explores the
      dynamic roles of macrophages in early and late central nervous system lentiviral
      disease. 

PMID- 25963555
TI  - Establishment of patient-derived cancer xenografts in immunodeficient NOG mice.
AB  - Viable and stable human cancer cell lines and animal models combined with
      adequate clinical information are essential for future advances in cancer
      research and patient care. Conventional in vitro cancer cell lines are commonly
      available; however, they lack detailed information on the patient from which they
      originate, including disease phenotype and drug sensitivity. Patient-derived
      xenografts (PDX) with clinical information (so-called 'cancer xenopatients') are
      a promising advance that may accelerate the development of anticancer therapies.
      We established 61 PDX lines from 116 surgically removed tumor tissues inoculated
      subcutaneously into NOG mice (53% success rate). PDX lines were established from
      various types of epithelial tumors and also from sarcomas, including
      gastrointestinal stromal tumors and Ewing/PNET sarcomas. The metastatic tumors
      yielded PDX lines more effectively (65%) than the primary tumors (27%, P<0.001).
      In our PDX models, morphological characteristics, gene expression profiles, and
      genetic alteration patterns were all well preserved. In eight cases (7%), the
      transplantable xenografts for several generations were composed of large
      monotonous nonepithelial cells of human origin, revealed to be Epstein-Barr virus
      infection-associated lympho-proliferative lesions. Despite this, PDX linked with
      clinical information offer many advantages for preclinical studies investigating
      new anticancer drugs. The fast and efficient establishment of individual PDX may
      also contribute to future personalized anticancer therapies.

PMID- 25963554
TI  - SIV encephalitis lesions are composed of CD163(+) macrophages present in the
      central nervous system during early SIV infection and SIV-positive macrophages
      recruited terminally with AIDS.
AB  - Macrophage recruitment to the central nervous system (CNS) during AIDS
      pathogenesis is poorly understood. We measured the accumulation of brain
      perivascular (CD163(+)) and inflammatory (MAC387(+)) macrophages in SIV-infected
      monkeys. Monocyte progenitors were 5-bromo-2'-deoxyuridine (BrdU) labeled in bone
      marrow, and CNS macrophages were labeled serially with fluorescent dextrans
      injected into the cisterna magna. MAC387(+) macrophages accumulated in the
      meninges and choroid plexus in early inflammation and in the perivascular space
      and SIV encephalitis (SIVE) lesions late. CD163(+) macrophages accumulated in the
      perivascular space and SIVE lesions with late inflammation. Most of the BrdU(+)
      cells were MAC387(+); however, CD163(+)BrdU(+) macrophages were present in the
      meninges and choroid plexus with AIDS. Most (81.6% +/- 1.8%) of macrophages in
      SIVE lesions were present in the CNS before SIVE lesion formation. There was a
      2.9-fold increase in SIVp28(+) macrophages entering the CNS late compared with
      those entering early (P < 0.05). The rate of CD163(+) macrophage recruitment to
      the CNS inversely correlated with time to death (P < 0.03) and increased with
      SIVE. In SIVE animals, soluble CD163 correlated with CD163(+) macrophage
      recruitment (P = 0.02). Most perivascular macrophages that comprise SIVE lesions
      and multinucleated giant cells are present in the CNS early, before SIVE lesions
      are formed. Most SIV-infected macrophages traffic to the CNS terminally with
      AIDS.

PMID- 25963556
TI  - Regulatory approaches to obesity prevention: A systematic overview of current
      laws addressing diet-related risk factors in the European Union and the United
      States.
AB  - High prevalence of overweight and obesity remains a significant international
      public health problem. Law has been identified as a tool for obesity prevention
      and selected high-profile measures have been reported. However, the nature and
      extent of enacted legislation internationally are unclear. This research provides
      an overview of regulatory approaches enacted in the United States, the European
      Union, and EU Member States since 2004. To this end, relevant databases of
      primary and secondary legislation were systematically searched to identify and
      explore laws addressing dietary risk factors for obesity. Across jurisdictions,
      current regulatory approaches to obesity prevention are limited in reach and
      scope. Target groups are rarely the general population, but instead sub
      populations in government-supported settings. Consumer information provision is
      preferred over taxation and marketing restrictions other than the regulation of
      health and nutrition claims. In the EU in particular, product reformulation with
      industry consent has also emerged as a popular small-scale measure. While
      consistent and widespread use of law is lacking, governments have employed a
      range of regulatory measures in the name of obesity prevention, indicating that
      there is, in principle, political will. Results from this study may serve as a
      starting point for future research and policy development. 

PMID- 25963557
TI  - DEGRO practical guidelines for radiotherapy of breast cancer V: Therapy for
      locally advanced and inflammatory breast cancer, as well as local therapy in
      cases with synchronous distant metastases.
AB  - AIM: The purpose of this work is to give practical guidelines for radiotherapy of
      locally advanced, inflammatory and metastatic breast cancer at first
      presentation. METHODS: A comprehensive survey of the literature using the search
      phrases "locally advanced breast cancer", "inflammatory breast cancer", "breast
      cancer and synchronous metastases", "de novo stage IV and breast cancer", and
      "metastatic breast cancer" and "at first presentation" restricted to "clinical
      trials", "randomized trials", "meta-analysis", "systematic review", and
      "guideline" was performed and supplemented by using references of the respective
      publications. Based on the German interdisciplinary S3 guidelines, updated in
      2012, this publication addresses indications, sequence to other therapies, target
      volumes, dose, and fractionation of radiotherapy. RESULTS: International and
      national guidelines are in agreement that locally advanced, at least if regarded
      primarily unresectable and inflammatory breast cancer should receive neoadjuvant
      systemic therapy first, followed by surgery and radiotherapy. If surgery is not
      amenable after systemic therapy, radiotherapy is the treatment of choice followed
      by surgery, if possible. Surgery and radiotherapy should be administered
      independent of response to neoadjuvant systemic treatment. In patients with a de
      novo diagnosis of breast cancer with synchronous distant metastases, surgery and
      radiotherapy result in considerably better locoregional tumor control. An
      improvement in survival has not been consistently proven, but may exist in
      subgroups of patients. CONCLUSION: Radiotherapy is an important part in the
      treatment of locally advanced and inflammatory breast cancer that should be given
      to all patients regardless to the intensity and effect of neoadjuvant systemic
      treatment and the extent of surgery. Locoregional radiotherapy in patients with
      primarily distant metastatic disease should be prescribed on an individual basis.

PMID- 25963558
TI  - Selective killing of K-ras-transformed pancreatic cancer cells by targeting
      NAD(P)H oxidase.
AB  - INTRODUCTION: Oncogenic activation of the K-ras gene occurs in >90% of pancreatic
      ductal carcinoma and plays a critical role in the pathogenesis of this
      malignancy. Increase of reactive oxygen species (ROS) has also been observed in a
      wide spectrum of cancers. This study aimed to investigate the mechanistic
      association between K-ras-induced transformation and increased ROS stress and its
      therapeutic implications in pancreatic cancer. METHODS: ROS level, NADPH oxidase
      (NOX) activity and expression, and cell invasion were examined in human
      pancreatic duct epithelial E6E7 cells transfected with K-ras (G12V) compared with
      parental E6E7 cells. The cytotoxic effect and antitumor effect of capsaicin, a
      NOX inhibitor, were also tested in vitro and in vivo. RESULTS: K-ras transfection
      caused activation of the membrane-associated redox enzyme NOX and elevated ROS
      generation through the phosphatidylinositol 3'-kinase (PI3K) pathway.
      Importantly, capsaicin preferentially inhibited the enzyme activity of NOX and
      induced severe ROS accumulation in K-ras-transformed cells compared with parental
      E6E7 cells. Furthermore, capsaicin effectively inhibited cell proliferation,
      prevented invasiveness of K-ras-transformed pancreatic cancer cells, and caused
      minimum toxicity to parental E6E7 cells. In vivo, capsaicin exhibited antitumor
      activity against pancreatic cancer and showed oxidative damage to the xenograft
      tumor cells. CONCLUSIONS: K-ras oncogenic signaling causes increased ROS stress
      through NOX, and abnormal ROS stress can selectively kill tumor cells by using
      NOX inhibitors. Our study provides a basis for developing a novel therapeutic
      strategy to effectively kill K-ras-transformed cells through a redox-mediated
      mechanism.

PMID- 25963559
TI  - Lytic enzyme-assisted germination of Bacillus anthracis and Bacillus subtilis
      spores.
AB  - AIMS: The goal of this work was to determine conditions under which external
      application of a spore germination-specific lytic enzyme (GSLE) can increase the
      germination efficiency of spore populations. METHODS AND RESULTS: The Bacillus
      anthracis GSLE SleB was applied to native and coat-disrupted B. anthracis and
      Bacillus subtilis spores. SleB was inactive on native spores but was able to
      trigger rapid germination of coat-disrupted spores. Using spores lacking their
      GSLEs or their germinant receptors to model poorly germinating spores, SleB
      application was able to increase colony-forming efficiency 100-fold for native
      spores and >1000-fold for coat-disrupted spores. SleB effects on GSLE-deficient
      spores were greater than on germinant receptor-deficient spores. CONCLUSIONS:
      SleB treatment can increase spore germination efficiency. The greater effect of
      SleB on coat-disrupted spores is presumably due to the greater access afforded to
      the cortex. However, SleB apparently gained access to the cortex of native spores
      after they responded to nutrients and completed stage I of germination, which may
      result in the disruption of coat structure. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Treatment of spore populations with a GSLE can increase germination efficiency.
      Such a treatment might be utilized to increase the rapid activation of industrial
      spore-based products.

PMID- 25963560
TI  - Microchip-based forensic short tandem repeat genotyping.
AB  - Micro total analysis system (MUTAS) or lab-on-a-chip (LOC) technology has
      advanced over decades, and the high performance for chemical and biological
      analysis has been well demonstrated with advantages of low sample consumption,
      rapid analysis time, high-throughput screening, and portability. In particular,
      MUTAS or LOC based genetic applications have been extensively explored, and the
      short tandem repeat (STR) typing on a chip has garnered attention in the forensic
      community due to its special use for human identification in the field of mass
      disaster and missing person investigation, paternity testing, and perpetrator
      identification. The STR typing process consists of sample collection, DNA
      extraction, DNA quantitation, STR loci amplification, capillary electrophoretic
      separation, and STR profiling. Recent progress of microtechnology shows its
      ability to substitute the conventional analytical tools, and furthermore
      demonstrates total integration of the whole STR processes on a single wafer for
      on-site STR typing. In this review article, we highlighted some representative
      results for fluorescence labeling techniques, microchip-based DNA purification,
      on-chip polymerase chain reaction (PCR), a capillary electrophoretic microdevice,
      and a fully integrated microdevice for STR typing. 

PMID- 25963561
TI  - The role of the dorsal hippocampus in two versions of the touchscreen automated
      paired associates learning (PAL) task for mice.
AB  - RATIONALE: The CANTAB object-location paired-associate learning (PAL) test can
      detect cognitive deficits in schizophrenia and Alzheimer's disease. A rodent
      version of touch screen PAL (dPAL) has been developed, but the underlying neural
      mechanisms are not fully understood. Although there is evidence that inactivation
      of the hippocampus following training leads to impairments in rats, this has not
      been tested in mice. Furthermore, it is not known whether acquisition, as opposed
      to performance, of the rodent version depends on the hippocampus. This is
      critical as many mouse models may have hippocampal dysfunction prior to the onset
      of task training. OBJECTIVES: The objectives of this study are to examine the
      effects of dorsal hippocampal (dHp) dysfunction on both performance and
      acquisition of mouse dPAL and to determine if hippocampal task sensitivity could
      be increased using a newly developed context-disambiguated PAL (cdPAL) paradigm.
      METHODS: In experiment 1, C57Bl/6 mice received post-acquisition dHp infusions of
      the GABA agonist muscimol. In experiment 2, C57Bl/6 mice received excitotoxic dHp
      lesions prior to dPAL/cdPAL acquisition. RESULTS: Post-acquisition muscimol dose
      dependently impaired dPAL and cdPAL performance. Pre-acquisition dHp lesions had
      only mild effects on both PAL tasks. Behavioural challenges including addition of
      objects and degradation of the visual stimuli with noise did not reveal any
      further impairments. CONCLUSIONS: dPAL and cdPAL performance is hippocampus
      dependent in the mouse, but both tasks can be learned in the absence of a
      functional dHp.

PMID- 25963562
TI  - Exposure to psychotropic medications prior to overdose: a case-control study.
AB  - RATIONALE: Little is known about psychotropic medication prescriptions prior to
      drug overdose. OBJECTIVES: We aimed to examine the possible associations between
      the risk of overdose and exposures to various psychotropic medications. METHODS:
      We conducted a matched case-control study of 3 groups of patients aged 12-74
      years, using a large-scale health insurance claims database in Japan (population
      1.2 million). A total of 351 cases with drug poisoning were compared with two
      control groups without overdose: 1755 patients with any treatment (general
      controls) and those with depression (high-risk controls). Current, past, and
      nonusers were patients most recently exposed to psychotropic medications <= 90
      days, 91-180 days, and >= 180 days before the index date. RESULTS: Current
      sedative-hypnotic use was associated with an increased odds of overdose relative
      to general control nonusers (odds ratio [OR], 21.5; 95 % confidence interval
      [CI], 9.7-47.8) and high-risk control nonusers (OR, 2.6; 95 % CI, 1.9-3.5). In
      the comparison of cases and high-risk controls, the ORs for overdose were higher
      among excessive dosage users than among usual dosage users (OR, 4.3; 95 % CI, 3.0
      6.1), among barbiturate users than among benzodiazepine/Z-drug only users (OR,
      4.5; 95 % CI, 2.3-8.7), and among multiple provider episodes than among single
      provider episodes (OR, 4.4; 95 % CI, 1.7-11.0). Psychiatrists prescribed more
      than 77 % of potentially questionable prescriptions. CONCLUSIONS: These results
      highlight the need for psychiatrists to monitor prescribed medications and
      balance the benefits and risks of pharmacological treatments.

PMID- 25963564
TI  - Prostratin: An Overview.
AB  - Terpenoid class of molecules possesses a diverse therapeutic properties and
      potentials owing to their specific structural features. Prostratin and its
      derivatives are exemplified in this context to exhibit a variety of biological
      activities. In this review we discuss in detail the role of prostratin as
      potential therapeutic and underlying molecular mechanisms by which it
      accomplishes these activities. Prostratin [13-O-acetyl-12-deoxyphorbol] is a
      phorbol ester that was first isolated from Strathmore weed Pimelea prostrate, a
      small endemic New Zealand shrub, and characterized by Hecker in 1976.
      Structurally, prostratin contains four rings designated as A, B, C and D. Ring A
      is trans linked to the 7-membered ring B while Ring C is a 6 membered and is cis
      linked to the cyclopentane ring D. Chemical synthesis of this compound initiated
      with acidic hydrolysis of phorbol, a tigliane diterpene isolated from croton oil.
      Prostratin-containing extracts have been used by the Samoan healers to treat
      individuals with certain medical conditions such as jaundice. Importantly, these
      treatments are not associated with any significant side effect. Prostratin
      inhibits HIV-1 infections by down regulating HIV-1 cellular receptors through the
      activation of protein kinase C (PKC) pathway and reduces the HIV-1 latency.
      Unlike other phorbol esters that induce carcinogenesis by activating PKC,
      prostratin does not induce tumors rather has shown tumor suppressing activity.
      Its ability to induce lytic gene expression supports a role for phorbol-ester
      regulated signaling pathways in Kaposi's sarcoma associated herpes-virus
      reactivation. 

PMID- 25963563
TI  - MAM (E17) rodent developmental model of neuropsychiatric disease: disruptions in
      learning and dysregulation of nucleus accumbens dopamine release, but spared
      executive function.
AB  - RATIONALE: Gestational day 17 methylazoxymethanol (MAM) treatment has been shown
      to reproduce, in rodents, some of the alterations in cortical and mesolimbic
      circuitries thought to contribute to schizophrenia. OBJECTIVE: We characterized
      the behavior of MAM animals in tasks dependent on these circuitries to see what
      behavioral aspects of schizophrenia the model captures. We then characterized the
      integrity of mesolimbic dopamine neurotransmission in a subset of animals used in
      the behavioral experiments. METHODS: MAM animals' capacity for working memory,
      attention, and resilience to distraction was tested with two different paradigms.
      Cue-reward learning and motivation were assayed with Pavlovian conditioned
      approach. Measurements of electrically stimulated phasic and tonic DA release in
      the nucleus accumbens with fast-scan cyclic voltammetry were obtained from the
      same animals used in the Pavlovian task. RESULTS: MAM animals' basic attentional
      capacities were intact. MAM animals took longer to acquire the working memory
      task, but once learned, performed at the same level as shams. MAM animals were
      also slower to develop a Pavlovian conditioned response, but otherwise no
      different from controls. These same animals showed alterations in terminal DA
      release that were unmasked by an amphetamine challenge. CONCLUSIONS: The
      predominant behavioral-cognitive feature of the MAM model is a learning
      impairment that is evident in acquisition of executive function tasks as well as
      basic Pavlovian associations. MAM animals also have dysregulated terminal DA
      release, and this may contribute to observed behavioral differences. The MAM
      model captures some functional impairments of schizophrenia, particularly those
      related to acquisition of goal-directed behavior.

PMID- 25963565
TI  - The Promise of Plant-Derived Substances as Inhibitors of Arginase.
AB  - The enzyme arginase catalyses the divalent cation dependent hydrolysis of L
      arginine to produce L-ornithine and urea. Two isoforms of arginases have been
      identified in mammalian (including human) cells. Moreover, some infectious
      pathogens (e.g. Leishmania) synthesize their own arginase. Work over the last
      decades has revealed that elevated arginase activity both decreases cellular
      availability in nitric oxide (NO) by competing with NO synthases (NOS) and
      increases concentration in L-ornithine, a precursor in the biosynthesis of
      polyamines which are important for cell differentiation and proliferation. From
      these data emerged the concept that selective arginase inhibitors might be a
      valuable strategy for treatment of various diseases associated with decreased NO
      and/or increased polyamines production. Consistent with this, recent research
      provides compelling evidence supporting the beneficial effects of arginase
      inhibitors in cardiovascular diseases (hypertension, ischemia reperfusion injury,
      atherosclerosis, diabetes mellitus), asthma, cancer, immunologically-mediated
      diseases or leishmaniasis. Despite active programs to identify potent arginase
      inhibitors, effective chemical compounds with reliable pharmacokinetics and
      toxicological properties are rare. The present review summarizes available data
      on the discovery of new arginase inhibitors from natural origin. Current
      knowledge on plant-derived compounds or extracts with arginase inhibitory
      properties as well as available data on structure-activity relationship (SAR)
      will be presented. Lastly, the present review will open up new prospects in order
      to improve the discovery of novel arginase inhibitors from natural sources. 

PMID- 25963566
TI  - Nanotechnology's Impact on Medicinal Chemistry.
AB  - Nanotechnology has intrigued a large number of researchers the world over owing
      to its unique properties as compared to bulk materials, and the novelty of
      applications made possible across many fields of science. Researchers, taking
      advantage of the unique properties of particles in nano (1-100 nm) form, have
      been developing nanoformulations of various medicinal compounds to enhance drug
      solubility, dissolution, and bioavailability. There are various methods by which
      drug compounds are conjugated to nanoparticles, and some bioactive compounds are
      attached by intermediary agents which are themselves usually part of the
      formation reaction of nanoparticles. Nanoformulations have been developed
      involving a range of medicinal compounds of biological and syntheticorigin
      intended to enhance the compound's pharmacokinetic and pharmacological profiles,
      or to capitalize on unique properties of nanoparticles for therapeutic or
      diagnostic purposes. A number of nanodrugs exist on the market today, and many
      more are in the clinical or pre-clinical pipeline. There are a number of
      challenges commonly encountered when designing nanodrug formulations as well as
      challenges to the long term viability of nanodrug formulation strategies,
      especially in regards to environmental and safety concerns. Some researchers have
      harnessed the structural and functional relationship of various medicinal
      compounds to enhance the design of nanoformulations. Other researchers have used
      structure-activity relationships as a means of enhancing safety and efficacy
      testing through in silico modeling. This article will touch on each of the above
      issues within the context of the impact each facet of nanotechnology has on
      medicinal chemistry.

PMID- 25963567
TI  - The Development of Protein Chips for High Throughput Screening (HTS) of
      Chemically Labeling Small Molecular Drugs.
AB  - How to construct protein chips and chemically labeling drug molecules without
      disrupting structures for HTS is still a challenging area. There are two main
      obstacles, one is that human multitrans membrane receptors, which are major drug
      targets, exhibit distinct motifs, and fold structures, and they will collapse
      unfold without membrane support in vitro; another one is that there still lack
      effective chemical labeling method for small drugs for detection. Therefore, how
      to acquire high detecting sensitivity for small molecules and to immobilize
      membrane protein receptors in native conformation with uniform direction on the
      chip, need to be solved for drug HTS. This paper reviews drug HTS trends in
      recent years, proposed a new virion-chip model and a feasible C-H activation
      method for CY-5 labeling drugs. It is expected to provide a good platform for
      future drug HTS. 

PMID- 25963568
TI  - Evaluating Potential P-gp Substrates: Main Aspects to Choose the Adequate
      Permeability Model for Assessing Gastrointestinal Drug Absorption.
AB  - The success of an oral drug route administration depends on many factors that
      interfere in its bioavailability, therapeutic efficacy and clinical safety. In
      human cells, ATP-dependent efflux transporter proteins, such as P-glycoprotein (P
      gp), BCRP and MRP2, reduce the absorption of drugs. A tiered approach chosen to
      evaluate drugs as substrates or inhibitors of efflux pumps, particularly P-gp,
      should be carefully selected, since each study method has advantages and
      intrinsic limitations to their processes. Depending on the adopted study
      conditions, the results may not correspond to the real characteristics of the
      drug regarding to its modulation by specific efflux proteins. This mini-review
      aims at summarizing the role of P-gp in the drugs oral absorption and correlating
      some of the most used permeability methods to determine the drug condition as P
      gp substrate. Studies about P-gp have shown that it is a dynamic protein,
      facilitating secretion of endogenous compounds, as aldosterone, and protecting
      cells against xenobiotics. Different efflux assays are employed to evaluate drugs
      as P-gp substrates. In an initial planning, MDCK-MDR1 tend to be the chosen
      method for efflux studies due its ability of express P-gp, followed by studies
      conducted in Caco-2 models. However, it is necessary to evaluate the advantages
      and disadvantages of each method to generate sound results and to set the
      correlation in vitro x in situ x in vivo. 

PMID- 25963569
TI  - The Recent Development of Farnesyltransferase Inhibitors as Anticancer and
      Antimalarial Agents.
AB  - Cancer is a serious disease characterized by the uncontrolled growth division of
      cells, and nowadays it remains a significant challenge for the medical field.
      Malaria is an infectious disease in the similar situation to cancer. Almost 40%
      people in the world live in areas with malaria risk and each year there are about
      2 to 3 million people dying from malaria. Farnesyltransferase (FTase) that
      belongs to isoprenyltransferase family can catalyze the initial step of Ras
      processing and is identified as a promising target for the treatment of cancer
      and malaria. During the past decade years, a large number of FTase inhibitors
      with anticancer or antimalarial activity have been reported and some of them are
      undergoing clinical development. This review mainly introduces the FTase
      inhibitors as anticancer and antimalarial agents, with focus on their enzyme
      inhibitory activity, stability and enzyme selectivity, etc. In particular, the
      promising new FTase inhibitors among them will be discussed in detail and the
      inspirations for their design will be highlighted. 

PMID- 25963570
TI  - New antitumour natural products from marine red algae: covering the period from
      2003 to 2012.
AB  - This review covers the 2003-2012 literature data published for natural products
      originating from marine red algae. The focus is on new antitumour substances,
      together with details related to the organism sourced. It emphasises 14 promising
      compounds (isolated from 13 species) whose chemical structures are briefly
      discussed.

PMID- 25963571
TI  - Environmental assessment of coastal surface sediments at Tarut Island, Arabian
      Gulf (Saudi Arabia).
AB  - Thirty eight surface sediments samples have been collected in the area around
      Tarut Island, Saudi Arabian Gulf to determine the spatial distribution of metals,
      and to assess the magnitude of pollution. Total concentrations of Fe, Mn, As, B,
      Cd, Co, Cr, Cu, Hg, Mo, Pb, Se, and Zn in the sediments were measured using ICP
      MS (Inductively Coupled Plasma-Mass Spectrometer). Nature of sediments and heavy
      metals distribution reflect marked changes in lithology, biological activities in
      Tarut bay. Very high arsenic concentrations were reported in all studied
      locations from Tarut Island. The concentrations of Mercury are generally high
      comparing to the reported values from the Gulf of Oman, Red Sea. The
      concentrations of As and Hg exceeded the wet threshold safety values (MEC, PEC)
      indicating possible As and Hg contamination. Dredging and land filling, sewage,
      and oil pollution are the most important sources of pollution in the study area. 

PMID- 25963572
TI  - Polybrominated Diphenyl Ethers (PBDEs) in Concepcion Bay, central Chile after the
      2010 Tsunami.
AB  - PBDEs (10 congeners) were analyzed using GC-MS in superficial sediments and
      organisms of the Concepcion Bay after the 2010 Tsunami. From all congeners
      analyzed PBDE-47, -99, -100 and -209 were the most frequently detected.
      Concentrations (ngg(-1) d.w.) in sediments for SigmaPBDE-47, -99, -100 were low
      (0.02-0.09). However, PBDE-209 showed significantly higher values ~20ngg(-1) d.w.
      This result were ~10 times lower than those reported in a previous study of the
      2010 Tsunami. The high result might be influenced by the massive urban debris
      dragged by the 2010 Tsunami. In organisms, concentrations of PBDE-47, -99, -100
      (~0.4ngg(-1) d.w.) were higher than those found in sediments (~0.04ngg(-1) d.w.).
      Differences in PBDE pattern were also observed between different levels of the
      trophic food chain (primary and secondary consumers). This is the first attempt
      to assess the current status of Concepcion Bay after the 2010 Tsunami. 

PMID- 25963573
TI  - Water-oil separation performance of technical textiles used for marine pollution
      disasters.
AB  - Oil is principally one of the most important energy sources in the world.
      However, as long as oil is explored and transported for being used, there will be
      the risk of the spillage into the marine environment. The use of technical
      textiles, i.e. fibrous beds, is a conventional separation technique for oil/water
      emulsion since it is efficient and easy to design. In this paper, the recovery of
      oil by technical textiles was mathematically modeled based on the structural
      parameters of textile and the capillary mechanism. Eleven types of commercial
      technical textiles with different properties were prepared for the experimental
      program. The experimental design included fiber type (polypropylene and
      polyester), fabric type (woven and/or nonwoven), fabric thickness and fabric
      areal density. Consequently, the absorption capacities of different technical
      textile samples were derived by the use of theoretical and experimental methods.
      The results show that there is a well fitness between theoretical outputs and
      experimental data. 

PMID- 25963574
TI  - Escherichia coli isolates from patients with bacteremic urinary tract infection
      are genetically distinct from those derived from sepsis following prostate
      transrectal biopsy.
AB  - BACKGROUND: Transrectal ultrasound-guided (TRUS) prostate biopsy is a very common
      procedure that is generally considered relatively safe. However, severe sepsis
      can occur after TRUS prostate biopsies, with Escherichia coli being the
      predominant causative agent. A common perception is that the bacteria that cause
      post-TRUS prostate biopsy infections originate in the urinary tract, but this
      view has not been adequately tested. Yet other authors believe on the basis of
      indirect evidence that the pathogens are introduced into the bloodstream by the
      biopsy needle after passage through the rectal mucosa. METHODS: We compared E.
      coli isolates from male patients with bacteremic urinary tract infection (B-UTI)
      to isolates of patients with post prostate biopsy sepsis (PPBS), in terms of
      their sequence types, determined by multi-locus sequence typing (MLST) and their
      virulence markers. RESULTS: B-UTI isolates were much richer in virulence genes
      than were PPBS isolates, supporting the hypothesis that E. coli causing PPBS
      derive directly from the rectum. Sequence type 131 (ST131) strains and related
      strain from the ST131 were common (>30%) among the E. coli isolates from PPBS
      patients as well as from B-UTI patients and all these strains expressed extended
      spectrum beta-lactamases. CONCLUSIONS: Our finding supports the hypothesis that
      E. coli causing PPBS derive directly from the rectum, bypassing the urinary
      tract, and therefore do not require many of the virulence capabilities necessary
      for an E. coli strain that must persist in the urinary tract. In light of the
      increasing prevalence of highly resistant E. coli strains, a new approach for
      prevention of PPBS is urgently required.

PMID- 25963575
TI  - Glycated serum albumin stimulates expression of endothelial cell specific
      molecule-1 in human umbilical vein endothelial cells: Implication in diabetes
      mediated endothelial dysfunction.
AB  - Pro-inflammatory conditions induced by products of protein glycation in diabetes
      substantially enhance the risk of endothelial dysfunction and related vascular
      complications. Endothelial cell specific molecule-1 (ESM-1) or endocan has been
      demonstrated as a potential biomarker in cancer and sepsis. Its role in diabetes
      induced pathologies remains unknown. The expression of ESM-1 gene is under
      cytokine regulation, indicating its role in endothelium-dependent pathological
      disorders. In this study, we investigated the effect of advanced glycated human
      serum albumin (AGE-HSA) on the production of ESM-1. We show that AGE-HSA exerts a
      modulating role on the expression of ESM-1 in human umbilical vein endothelial
      cells. It up-regulates expression of ESM-1 protein in a dose-dependent manner
      which correlates with its messenger RNA (mRNA) transcription. RAGE and galectin
      3, both AGE receptors, show antagonistic action on its expression. While gene
      silencing of RAGE has down-regulatory effect, that of galectin-3 has up
      regulatory effect on AGE-induced expression of ESM-1. Inhibition of MAPKKK and
      JNK pathways did not alter the expression. In contrast, phosphatidylinositol 3
      kinase (PI3K) inhibition significantly up-regulated ESM-1 expression. In
      conclusion, these results suggest that AGE-induced activation of human umbilical
      vein endothelial cells promotes formation of endocan which is an endothelial
      dysfunction marker and may be related to vascular disease in diabetes. 

PMID- 25963576
TI  - Effect of toluene concentration and hydrogen peroxide on Pseudomonas
      plecoglossicida cometabolizing mixture of cis-DCE and TCE in soil slurry.
AB  - An indigenous Pseudomonas sp., isolated from the regional contaminated soil and
      identified as P. plecoglossicida, was evaluated for its aerobic cometabolic
      removal of cis-1,2-dichloroethylene (cis-DCE) and trichloroethylene (TCE) using
      toluene as growth substrate in a laboratory-scale soil slurry. The aerobic
      simultaneous bioremoval of the cis-DCE/TCE/toluene mixture was studied under
      different conditions. Results showed that an increase in toluene concentration
      level from 300 to 900 mg/kg prolonged the lag phase for the bacterial growth,
      while the bioremoval extent for cis-DCE, TCE, and toluene declined as the initial
      toluene concentration increased. In addition, the cometabolic bioremoval of cis
      DCE and TCE was inhibited by the presence of hydrogen peroxide as the additional
      oxygen source, while the bioremoval of toluene (900 mg/kg) was enhanced after 9
      days of incubation. The subsequent addition of toluene did not improve the
      cometabolic bioremoval of cis-DCE and TCE. The obtained results would help to
      enhance the applicability of bioremediation technology to the mixed waste
      contaminated sites.

PMID- 25963577
TI  - Digging deeper into noise: Reply to comment on "Extracting physics of life at the
      molecular level: A review of single-molecule data analyses".

PMID- 25963578
TI  - One-step direct synthesis of layered double hydroxide single-layer nanosheets.
AB  - Layered double hydroxide (LDH) single-layer nanosheets were traditionally
      prepared through a multi-step exfoliation process which is very time-consuming
      and of low efficiency. Herein we report the preparation of LDH single-layer
      nanosheets through a facile direct synthesis method. By introducing a layer
      growth inhibitor, one can directly synthesize LDH single-layer nanosheets instead
      of LDH layered compounds. The inhibitor weakens the interactions between
      neighboring layers, thus preventing the interlayer growth. This investigation on
      blocking interlayer growth by weakening interlayer interactions to obtain
      inorganic single-layer nanosheets opens a new route for the synthesis of 2
      dimensional materials. 

PMID- 25963580
TI  - Standardized counting of circulating platelet microparticles using currently
      available flow cytometers and scatter-based triggering: Forward or side scatter?
AB  - Clinical determination of MP counts using flow cytometry has not been fully
      accepted yet due to the lack of standardization protocols. In the past 5 years,
      we have proposed two versions of a method with reproducible PMP counts in plasma
      samples. Both methods use forward scatter (FSC)-based threshold set with
      reference beads of appropriate sizes; first using 0.5 um beads and later with 0.3
      um beads. Both systems provide reproducible PMP counts. However, this technique
      works only with some of currently used commercial flow cytometers. Instruments
      with limited resolution or generating heterogeneous FSC signals are excluded.
      Such performances are incompatible with the required interinstrument
      standardization. Here we show that (i) flow cytometers with sub-optimal FSC
      capabilities generally have higher SSC resolution and background rejection
      capacity, and (ii) that the same biological entities, "dim and bright PMP," both
      can be counted using alternative strategies, either as previously described,
      based on FSC measurements, or as presented here, based on SSC detection. The
      critical element in the standardization protocol is the use of different sizes of
      reference beads. This study was designed to permit simultaneous access to both
      FSC- and SSC-optimized platforms. A new range of about 0.17-0.6 um eq. (um
      equivalents) is proposed for an alternative SSC-based MP gate generating the same
      PMP counts as those obtained in the previously proposed 0.3-1 um eq. FSC-based MP
      gate. The two equivalent standardization options reconcile intrinsically
      different scattering behaviors between SSC- and FCS--triggered instruments and
      open the opportunity for multicenter studies in the future.

PMID- 25963581
TI  - Analysis of mechanisms for memory enhancement using novel and potent 5-HT1A
      receptor ligands.
AB  - In light of the involvement of serotonergic 5-HT1A receptors in the mediation of
      the memory of aversive events, the potent and selective 5-HT1A receptor
      antagonists, MC18 fumarate and VP08/34 fumarate, were tested in the passive
      avoidance task (PA), a rodent model of instrumental conditioning. Either alone or
      in combination with the prototypical agonist 8-OH-DPAT, MC18 fumarate at doses
      (0.1, 0.3 and 1mg/kg given 15min prior to training) exerted a dose-dependent
      facilitation of PA memory retention. When administered 15min prior to 8-OH-DPAT
      (0.3 and 1mg/kg), MC18 fumarate at a dose of 0.3mg/kg, enhanced significantly the
      impairment of PA retention caused by 8-OH-DPAT (1mg/kg). However, VP08/34
      fumarate given at the same doses exerted no statistically effect on PA retention
      memory. Furthermore, VP08/34 fumarate given 15min prior to 8-OH-DPAT (0.3 and
      1mg/kg) only slightly enhanced the PA impairment induced by 8-OH-DPAT. In
      conclusion, the profile of MC18 fumarate is intriguing since it behaves in a
      manner which differs from both full receptor antagonists such as NAD-299 or
      partial receptor agonists. The results also illustrate the importance of subtle
      receptor interaction and probably ligand efficacy in determining the actions of
      two almost identical 5-HT1A receptor ligands in cognitive function such as
      instrumental learning. 

PMID- 25963582
TI  - Effect of Varying Magnetic Fields on Targeted Gene Delivery of Nucleic Acid-Based
      Molecules.
AB  - Several physical methods have been developed to introduce nucleic acid expression
      vectors into mammalian cells. Magnetic transfection (magnetofection) is one such
      transfection method, and it involves binding of nucleic acids such as DNA, RNA or
      siRNA to magnetic nanoparticles followed by subsequent exposure to external
      magnetic fields. However, the challenge between high efficiency of nucleic acid
      uptake by cells and toxicity was not totally resolved. Delivery of nucleic acids
      and their transport to the target cells require carefully designed and controlled
      systems. In this study, we introduced a novel magnetic system design providing
      varying magnet turn speeds and magnetic field directions. The system was tested
      in the magnetofection of human breast (MCF-7), prostate (DU-145, PC-3) and
      bladder (RT-4) cancer cell lines using green fluorescent protein DNA as a
      reporter. Polyethylenimine coated superparamagnetic iron oxide nanoparticles
      (SPIONs) were used as nucleic acid carriers. Adsorption of PEI on SPION improved
      the cytocompatibility dramatically. Application of external magnetic field
      increased intracellular uptake of nanoparticles and transfection efficiency
      without any additional cytotoxicity. We introduce our novel magnetism-based
      method as a promising tool for enhanced nucleic acid delivery into mammalian
      cells. 

PMID- 25963579
TI  - Systematic Literature Review of the Methods Used to Compare Newer Second
      Generation Agents for the Management of Schizophrenia: A focus on Health
      Technology Assessment.
AB  - BACKGROUND: The challenges of comparative effectiveness to support health
      technology assessment (HTA) agencies are important considerations in the choices
      of antipsychotic medications for the treatment of schizophrenia. OBJECTIVES: Our
      aim was to assess the study methods used and outcomes reported in the published
      literature to address the question of comparative effectiveness of newer
      antipsychotic agents and the adequacy and availability of evidence to support HTA
      agencies. DATA SOURCE: A systematic search of the PubMed database from 1 January
      2009 to 30 September 2013 was conducted to identify studies evaluating new
      atypical antipsychotics reporting on comparative effectiveness. STUDY SELECTION:
      The systematic review comprised of studies on schizophrenia patients where at
      least two drugs were being compared and at least one treatment group received one
      of the following second-generation antipsychotics: risperidone, olanzapine,
      aripiprazole, paliperidone, asenapine, iloperidone, lurasidone, and quetiapine.
      The included studies were also required to have an efficacy, safety or economic
      outcome, such as Positive and Negative Syndrome Scale (PANSS) score, weight gain,
      resource utilization, or costs. STUDY APPRAISAL AND SYNTHESIS METHODS: Two
      reviewers (BW and GK) independently applied the inclusion criteria. Disagreements
      between reviewers were resolved by consensus, referring to the original sources.
      Information on the methodology and outcomes was collected for each included
      study. This included study description, head-to-head drug comparison, patient
      population, study methodology, statistical methods, reported outcomes, study
      support, and journal type. RESULTS: A total of 198 studies were identified from
      electronic search methods. The largest category of studies was randomized
      controlled trials [RCTs] (N = 73; 36.9%), which were largely directed at the
      regulatory endpoint. Fewer studies were undertaken for HTA-purposes cohort
      studies (N = 53; 26.8%), meta-analyses (N = 32; 16.2%), economic studies (N = 14;
      7.1%), and cross-sectional studies (N = 13; 6.6%). Direct head-to-head
      comparisons preferred by HTA were dominated by the comparison involving
      olanzapine and risperidone, representing 149 (75.3%) and 119 (60.1%) studies,
      respectively. RCTs, which are the primary study type for regulatory submissions,
      showed a lack of bias. Studies aimed at HTA were not as well performed. Cohort
      studies suffered from bias in the selection of comparison groups, lack of control
      for confounders, and differential dropout rates. As a group, cross-sectional
      studies scored poorly for bias, with a primary failure to identify a
      representative sample. Economic studies showed highly variable bias, with bias in
      the representation of effectiveness data, model assumptions without validation,
      and lack of sensitivity analyses. LIMITATIONS: One limitation of this systematic
      review is that it only included studies from 2009 to 2013, potentially excluding
      some earlier comparator studies, particularly those involving first-generation
      antipsychotics. CONCLUSIONS: This review of comparative effectiveness studies of
      second-generation antipsychotic agents for schizophrenic patients revealed a wide
      range of study types, study methodologies, and outcomes. For traditional efficacy
      outcomes and select safety outcomes, there is strong evidence from many well
      conducted studies; however, there are fewer studies of types preferred by HTA
      with limited head-to-head comparisons and a higher risk of bias in the execution
      of these studies.

PMID- 25963583
TI  - Verapamil hepatic clearance in four preclinical rat models: towards activity
      based scaling.
AB  - The current study was designed to cross-validate rat liver microsomes (RLM),
      suspended rat hepatocytes (SRH) and the isolated perfused rat liver (IPRL) model
      against in vivo pharmacokinetic data, using verapamil as a model drug. Michaelis
      Menten constants (Km), for the metabolic disappearance kinetics of verapamil in
      RLM and SRH (freshly isolated and cryopreserved), were determined and corrected
      for non-specific binding. The 'unbound' Km determined with RLM (2.8 uM) was
      divided by the 'unbound' Km determined with fresh and cryopreserved SRH (3.9 uM
      and 2.1 uM, respectively) to calculate the ratio of intracellular to
      extracellular unbound concentration (Kpu,u). Kpu,u was significantly different
      between freshly isolated (0.71) and cryopreserved (1.31) SRH, but intracellular
      capacity for verapamil metabolism was maintained after cryopreservation (200 vs.
      191 ul/min/million cells). Direct comparison of intrinsic clearance values
      (Clint) in RLM versus SRH, yielded an activity-based scaling factor (SF) of 0.28
      0.30 mg microsomal protein/million cells (MPPMC). Merging the IPRL-derived Clint
      with the MPPMC and SRH data, resulted in scaling factors for MPPGL (80 and 43 mg
      microsomal protein/g liver) and HPGL (269 and 153 million cells/g liver),
      respectively. Likewise, the hepatic blood flow (61 ml/min/kg b.wt) was calculated
      using IPRL Clint and the in vivo Cl. The scaling factors determined here are
      consistent with previously reported CYP450-content based scaling factors.
      Overall, the results show that integrated interpretation of data obtained with
      multiple preclinical tools (i.e. RLM, SRH, IPRL) can contribute to more reliable
      estimates for scaling factors and ultimately to improved in vivo clearance
      predictions based on in vitro experimentation.

PMID- 25963584
TI  - Knowing it When You See it: The Need for Continuing Innovation in Research on
      Healthcare Discrimination.

PMID- 25963585
TI  - Effects of Anaerobic Training on Paraoxonase-1 Enzyme (PON1) Activities of High
      Density Lipoprotein Subgroups and Its Relationship with PON1-Q192R Phenotype.

PMID- 25963586
TI  - Effect of EDTA conditioning on cervical restorations bonded with a self-etch
      adhesive: A randomized double-blind clinical trial.
AB  - OBJECTIVE: To compare the 18-month retention rates of composite restorations in
      non-carious cervical lesions [NCCLs] bonded with a self-etch adhesive with and
      without preliminary conditioning with EDTA. METHODS: Forty-eight patients with
      two similar-sized NCCL were selected and randomly allocated to one of two groups.
      Two calibrated operators placed 96 restorations with a one-step self-etch
      adhesive (Adper Easy One, 3M ESPE). Half of the restorations were placed
      according to the manufacturer's instructions while, for the other half, the
      surfaces of the lesions were conditioned with 17% EDTA for 2 min prior to
      adhesive application. Two blinded and independent examiners evaluated the
      restorations at baseline, 6, 12, and 18 months, according to the FDI criteria.
      The comparison between groups in each period was conducted with the Fisher's
      exact test, and the performance of each group at the different periods was
      evaluated by McNemar's test (alpha=0.05). RESULTS: After 18 months, significantly
      higher retention rates (95% CI) were observed for the EDTA group (95.5 [84.9
      98.7]) than the control group (79.6% [65.5-88.9]) (p=0.02). Significant
      deterioration of the marginal adaptation and marginal discoloration were observed
      for both groups over the 18-month evaluation. CONCLUSIONS: The preliminary
      conditioning with EDTA before application of a one-step self-etch adhesive
      significantly improved the retention rates of composite restorations in cervical
      lesions. CLINICAL SIGNIFICANCE: Conditioning with EDTA is an alternative that
      improves the 18-month retention rate of cervical restorations bonded with a self
      etch adhesive.

PMID- 25963587
TI  - Public perceptions of dental implants: a qualitative study.
AB  - OBJECTIVES: Dental implants have become a popular option for treating partially
      dentate or edentulous patients. Information on dental implants is widely
      available in the public domain and is disseminated through industries and dental
      practitioners at various levels/disciplines. This qualitative study aimed to
      evaluate the public's information acquisition and their perceptions of dental
      implants and the effects of these on their care-seeking and decision making.
      METHODS: A purposive sample of 28 adults were recruited to join six focus groups.
      To be eligible, one must be 35-64 years of age, had never been engaged in
      dentally related jobs, had at least one missing tooth, and had heard about dental
      implant but never received dental implant or entered into any dental consultation
      regarding dental implants. All of the focus groups discussions were transcribed
      verbatim and subjected to thematic content analysis following a grounded theory
      approach. RESULTS: Participants acquired information on dental implants through
      various means, such as patient information boards, printed advertisements, social
      media, and personal connections. They expected dental implants to restore the
      patients' appearance, functions, and quality of life to absolute normality. They
      regarded dental implants as a panacea for all cases of missing teeth,
      overestimated their functions and longevity, and underestimated the expertise
      needed to carry out the clinical procedures. They were deterred from seeking
      dental implant treatment by the high price, invasive procedures, risks, and
      complications. CONCLUSIONS: Members of the public were exposed to information of
      varying quality and had some unrealistic expectations regarding dental implants.
      Such perceptions may shape their care-seeking behaviours and decision-making
      processes in one way or another. CLINICAL SIGNIFICANCE: The views and experiences
      gathered in this qualitative study could assist clinicians to better understand
      the public's perspectives, facilitate constructive patient-dentist communication,
      and contribute to the creation of positive clinical experiences in implant
      dentistry.

PMID- 25963588
TI  - Chronic kidney disease: Actin cytoskeleton alterations in podocytes: a
      therapeutic target for chronic kidney disease.

PMID- 25963589
TI  - Podocyte biology: Free fatty acid-induced macropinocytosis in podocytes.

PMID- 25963590
TI  - Urinary tract infection: Ceftolozane-tazobactam gives a new ASPECT to the fight
      against antimicrobial resistance.

PMID- 25963591
TI  - Microbiota-implications for immunity and transplantation.
AB  - Each individual harbours a unique set of commensal microorganisms, collectively
      referred to as the microbiota. Notably, these microorganisms exceed the number of
      cells in the human body by 10-fold. This finding has accelerated a shift in our
      understanding of human physiology, with the realization that traits necessary for
      health are both encoded and influenced by the human genome and the microbiota.
      Our understanding of the aetiology of complex diseases has, therefore, evolved
      with increasing awareness that the human microbiota has an active and critical
      role in maintaining health and inducing disease. Indeed, findings from
      bioinformatic studies indicate that the microbiota and microbiome have multiple
      effects on the innate and adaptive immune systems, with effects on infection,
      autoimmune disease and cancer. In this Review, we first address the important
      statistical and informatics aspects that should be considered when characterizing
      the composition of microbiota. We next highlight the effects of the microbiota on
      the immune system and the implications of these effects on organ failure and
      transplantation. Finally, we reflect on the future perspectives for studies of
      the microbiota, including novel diagnostic tests and therapeutics. 

PMID- 25963592
TI  - The use of lineage tracing to study kidney injury and regeneration.
AB  - Lineage tracing is a powerful tool to track cells in vivo and provides enhanced
      spatial, temporal, and kinetic resolution of the mechanisms that underlie tissue
      renewal and repair. The data obtained from novel mouse models engineered for
      lineage tracing has started to transform our understanding of the changes in cell
      fate that underlie renal pathophysiology, the role of stem and/or progenitor
      cells in kidney development, and the mechanisms of kidney regeneration. The
      complexity of the genetic systems that are engineered for lineage tracing
      requires careful analysis and interpretation. In this Review we emphasize that
      close attention in lineage tracing studies must be paid to the specificity of the
      promoter, the use of drug-controlled activation of Cre recombinase as a genetic
      switch, and the type of reporter that should be engineered into lineage tracing
      genetic constructs. We evaluate the optimal experimental conditions required to
      achieve the pre-specified aims of the study and discuss the novel genetic
      techniques that are becoming available to study putative renal progenitor cells
      and the mechanisms of kidney regeneration. 

PMID- 25963593
TI  - Risk factors: Individual assessment of CKD risk in HIV-positive patients.

PMID- 25963595
TI  - Tumour-associated mast cells in classical Hodgkin's lymphoma: correlation with
      histological subtype, other tumour-infiltrating inflammatory cell subsets and
      outcome.
AB  - The tumour microenvironment in classical Hodgkin's lymphoma (cHL) is
      characterised by a minor population of neoplastic Hodgkin and Reed-Sternberg
      cells within a heterogeneous background of non-neoplastic bystanders cells,
      including mast cells. The number of infiltrating mast cells in cHL has been
      reported to correlate with poor prognosis. We used immunohistochemistry to assess
      the degree of tumour-infiltrating mast cells in cHL tissue microarrays and
      correlated this with clinico-pathological features and prognosis in a cohort of
      homogeneously treated patients with Hodgkin's disease. A high degree of tumour
      mast cells was associated with nodular sclerosis (NS) subtype histology (P =
      0.0002). Moreover, the number of mast cells was inversely correlated with the
      numbers of CD68+ and CD163+ macrophages (P = 0.0001 and P = 0.003, respectively)
      and with the number of granzyme+ cytotoxic cells (P = 0.004). The degree of mast
      cell infiltration was not a prognostic factor in cHL of nodular sclerosis
      subtype. In contrast, in mixed cellularity cHL a high number of intratumoral mast
      cells correlated with significantly poorer outcome both in terms of overall (P =
      0.03) and event-free survival (P = 0.01). Further studies are warranted into the
      biological mechanisms underlying this adverse outcome and their possible
      therapeutic implications.

PMID- 25963596
TI  - Should we screen for childhood obesity?

PMID- 25963594
TI  - Magnesium and cardiovascular complications of chronic kidney disease.
AB  - Cardiovascular complications are the leading cause of death in patients with
      chronic kidney disease (CKD). Abundant experimental evidence suggests a
      physiological role of magnesium in cardiovascular function, and clinical evidence
      suggests a role of the cation in cardiovascular disease in the general
      population. The role of magnesium in CKD-mineral and bone disorder, and in
      particular its impact on cardiovascular morbidity and mortality in patients with
      CKD, is however not well understood. Experimental studies have shown that
      magnesium inhibits vascular calcification, both by direct effects on the vessel
      wall and by indirect, systemic effects. Moreover, an increasing number of
      epidemiologic studies in patients with CKD have shown associations of serum
      magnesium levels with intermediate and hard outcomes, including vascular
      calcification, cardiovascular events and mortality. Intervention trials in these
      patients conducted to date have had small sample sizes and have been limited to
      the study of surrogate parameters, such as arterial stiffness, vascular
      calcification and atherosclerosis. Randomized controlled trials are clearly
      needed to determine the effects of magnesium supplementation on hard outcomes in
      patients with CKD. 

PMID- 25963597
TI  - Expression profile of IGF-I-calcineurin-NFATc3-dependent pathway genes in
      skeletal muscle during early development between duck breeds differing in growth
      rates.
AB  - The insulin-like growth factor I (IGF-I)-calcineurin (CaN)-NFATc signaling
      pathways have been implicated in the regulation of myocyte hypertrophy and fiber
      type specificity. In the present study, the expression of the CnAalpha, NFATc3,
      and IGF-I genes was quantified by RT-PCR for the first time in the breast muscle
      (BM) and leg muscle (LM) on days 13, 17, 21, 25, and 27 of embryonic development,
      as well as at 7 days posthatching (PH), in Gaoyou and Jinding ducks, which differ
      in their muscle growth rates. Consistent expression patterns of CnAalpha, NFATc3,
      and IGF-I were found in the same anatomical location at different development
      stages in both duck breeds, showing significant differences in an age-specific
      fashion. However, the three genes were differentially expressed in the two
      different anatomical locations (BM and LM). CnAalpha, NFATc3, and IGF-I messenger
      RNA (mRNA) could be detected as early as embryonic day 13 (ED13), and the highest
      level appeared at this stage in both BM and LM. Significant positive
      relationships were observed in the expression of the studied genes in the BM and
      LM of both duck breeds. Also, the expression of these three genes showed a
      positive relationship with the percentage of type IIb fibers and a negative
      relationship with the percentage of type I fibers and type IIa fibers. Our data
      indicate differential expression and coordinated developmental regulation of the
      selected genes involved in the IGF-I-calcineurin-NFATc3 pathway in duck skeletal
      muscle during embryonic and early PH growth and development; these data also
      indicate that this signaling pathway might play a role in the regulation of
      myofiber type transition. 

PMID- 25963598
TI  - Molecular Outcome, Prediction, and Clinical Consequences of Splice Variants in
      COL1A1, Which Encodes the proalpha1(I) Chains of Type I Procollagen.
AB  - Approximately 10%-20% of germline pathogenic variants alter mRNA splicing, with
      phenotypes often dependent on the stability of the mRNA produced by the mutant
      allele. To better understand the relationships between genotype, mRNA splicing,
      and phenotype, we examined clinical and molecular data from 243 probands with
      osteogenesis imperfecta (OI) representing 145 unique splicing variants within the
      type I procollagen gene, COL1A1. All individuals with IVSX-1G>A mutations had OI
      type I because the substitution shifted the splice acceptor site 1 nt downstream
      and destabilized the mRNA. OI phenotypes were not consistent for any other splice
      variant identified. We sequenced all cDNA species from cultured dermal
      fibroblasts from 40 individuals to identify splice outcome and compared those
      results to splice predictions from Human Splice Finder (HSF), Spliceport (SP),
      and Automatic Splice Site and Exon Definition Analyses (ASSEDA). Software-based
      splice predictions were correct in 42%, 55%, and 74% instances for HSF, SP, and
      ASSEDA, respectively. As molecular diagnostics move increasingly to DNA sequence
      analysis, the need to understand the effects of splice site variants will
      increase. These data demonstrate that caution must be exercised when using splice
      prediction software to predict splice outcome. 

PMID- 25963599
TI  - Treating cancer with infection: a review on bacterial cancer therapy.
AB  - There is an increasing need for new cancer therapies. The antitumour effect of
      bacterial infection has been well observed and practiced throughout history.
      Bacteria are well-suited to serve as anticancer agents due to their intrinsic
      mobility, cell toxicity, immunogenicity, and preferential accumulation within the
      anoxic tumour environment. Furthermore, advances in biotechnology and molecular
      techniques have made it easier than ever to engineer bacteria as both therapeutic
      agents themselves and as therapeutic vectors. Here, we review bacteriolytic
      therapy and immunotherapy strategies, and examine the development of bacteria as
      vehicles for cell- and tissue-targeted delivery of genetic cancer therapeutics. 

PMID- 25963600
TI  - Extended flowering intervals of bamboos evolved by discrete multiplication.
AB  - Numerous bamboo species collectively flower and seed at dramatically extended,
      regular intervals - some as long as 120 years. These collective seed releases,
      termed 'masts', are thought to be a strategy to overwhelm seed predators or to
      maximise pollination rates. But why are the intervals so long, and how did they
      evolve? We propose a simple mathematical model that supports their evolution as a
      two-step process: First, an initial phase in which a mostly annually flowering
      population synchronises onto a small multi-year interval. Second, a phase of
      successive small multiplications of the initial synchronisation interval,
      resulting in the extraordinary intervals seen today. A prediction of the
      hypothesis is that mast intervals observed today should factorise into small
      prime numbers. Using a historical data set of bamboo flowering observations, we
      find strong evidence in favour of this prediction. Our hypothesis provides the
      first theoretical explanation for the mechanism underlying this remarkable
      phenomenon.

PMID- 25963601
TI  - An inverse problem formulation for parameter estimation of a reaction-diffusion
      model of low grade gliomas.
AB  - We present a numerical scheme for solving a parameter estimation problem for a
      model of low-grade glioma growth. Our goal is to estimate the spatial
      distribution of tumor concentration, as well as the magnitude of anisotropic
      tumor diffusion. We use a constrained optimization formulation with a reaction
      diffusion model that results in a system of nonlinear partial differential
      equations. In our formulation, we estimate the parameters using partially
      observed, noisy tumor concentration data at two different time instances, along
      with white matter fiber directions derived from diffusion tensor imaging. The
      optimization problem is solved with a Gauss-Newton reduced space algorithm. We
      present the formulation and outline the numerical algorithms for solving the
      resulting equations. We test the method using a synthetic dataset and compute the
      reconstruction error for different noise levels and detection thresholds for
      monofocal and multifocal test cases. 

PMID- 25963602
TI  - Reduction in food away from home is associated with improved child relative
      weight and body composition outcomes and this relation is mediated by changes in
      diet quality.
AB  - BACKGROUND: Reducing consumption of food away from home is often targeted during
      pediatric obesity treatment, given the associations with weight status and gain.
      However, the effects of this dietary change on weight loss are unknown.
      OBJECTIVE: Our aim was to evaluate associations between changes in dietary
      factors and child anthropometric outcomes after treatment. It is hypothesized
      that reduced consumption of food away from home will be associated with improved
      dietary intake and greater reductions in anthropometric outcomes (standardized
      body mass index [BMI] and percent body fat), and the relationship between food
      away from home and anthropometric outcomes will be mediated by improved child
      dietary intake. DESIGN: We conducted a longitudinal evaluation of associations
      between dietary changes and child anthropometric outcomes. Child diet (three 24
      hour recalls) and anthropometric data were collected at baseline and 16 weeks.
      PARTICIPANTS/SETTING: Participants were 170 overweight and obese children ages 7
      to 11 years who completed a 16-week family-based behavioral weight-loss treatment
      as part of a larger multi-site randomized controlled trial conducted in two
      cohorts between 2010 and 2011 (clinical research trial). INTERVENTION: Dietary
      treatment targets during family-based behavioral weight-loss treatment included
      improving diet quality and reducing food away from home. MAIN OUTCOME MEASURES:
      The main outcome measures in this study were child relative weight (standardized
      BMI) and body composition (percent body fat). STATISTICAL ANALYSES: We performed
      t tests and bootstrapped single-mediation analyses adjusting for relevant
      covariates. RESULTS: As hypothesized, decreased food away from home was
      associated with improved diet quality and greater reductions in standardized BMI
      (P<0.05) and percent body fat (P<0.01). Associations between food away from home
      and anthropometric outcomes were mediated by changes in diet quality.
      Specifically, change in total energy intake and added sugars mediated the
      association between change in food away from home and standardized BMI, and
      change in overall diet quality, fiber, added sugars, and added fats mediated the
      association between change in food away from home and percent body fat. Including
      physical activity as a covariate did not significantly impact these findings.
      CONCLUSIONS: These results suggest that reducing food away from home can be an
      important behavioral target for affecting positive changes in both diet quality
      and anthropometric outcomes during treatment.

PMID- 25963603
TI  - The Influence of a Factitious Free-From Food Product Label on Consumer
      Perceptions of Healthfulness.
AB  - BACKGROUND: Given the rapid rise of free-from products available in the
      marketplace (especially gluten-free), more research is needed to understand how
      these products influence consumer perceptions of healthfulness. OBJECTIVE: To
      determine whether perceptions of healthfulness can be generated about free-from
      products in the absence of risk information. DESIGN: A survey was administered to
      256 adults. Two picture-based food product questions evaluated which products
      consumers perceived to be healthier. One free-from designation was fabricated
      (MUI-free), whereas gluten-free was used as the comparison designation. For each
      question, participants chose which product they thought was healthier (free-from,
      conventional, or equally healthy). STATISTICAL ANALYSES: A chi(2) test was run to
      assess the difference between responses to picture-based food product questions.
      Multinomial regression assessed variance in responses attributable to participant
      demographic characteristics. RESULTS: Among the respondents, 21.9% selected the
      MUI-free product as healthier, whereas 25.5% selected the gluten-free product as
      healthier. Frequency data showed that a significant number of participants chose
      both free-from products as healthier than the conventional products (P<0.001).
      Regression analysis found that individuals who identified as gluten intolerant or
      unsure of a gluten intolerance were significantly more likely than other
      participants to choose the free-from product as healthier compared with choosing
      "equally healthy" (P=0.040). Hispanics and those with an associate's degree or
      vocational training were significantly more likely than their referent groups
      (whites and those with a doctoral degree, respectively) to choose the free-from
      product as healthier compared with choosing "equally healthy" (P=0.022 and 0.034,
      respectively). Finally, African Americans were more likely than whites to choose
      the conventional product as healthier compared with choosing "equally healthy"
      (P=0.016). CONCLUSIONS: Frequency data demonstrated that free-from products can
      generate perceptions of healthfulness in the absence of risk information. Self
      reported intolerance data suggest that individuals with a heightened concern
      about the risks associated with gluten may perceive the larger category of free
      from products as more healthful. In addition, ethnicity and education level
      appear to play a role in free-from product perception.

PMID- 25963605
TI  - Ectomycorrhizal fungal communities coinvading with Pinaceae host plants in
      Argentina: Gringos bajo el bosque.
AB  - Coinvasive ectomycorrhizal (ECM) fungi allow Pinaceae species to invade regions
      otherwise lacking compatible symbionts, but ECM fungal communities permitting
      Pinaceae invasions are poorly understood. In the context of Pinaceae invasions on
      Isla Victoria, Nahuel Huapi National Park, Argentina, we asked: what ECM fungi
      are coinvading with Pinaceae hosts on Isla Victoria; are some ECM fungal species
      or genera more prone to invade than others; and are all ECM fungal species that
      associate with Northern Hemisphere hosts also nonnative, or are some native fungi
      compatible with nonnative plants? We sampled ECMs from 226 Pinaceae host plant
      individuals, both planted individuals and recruits, growing inside and invading
      from plantations. We used molecular techniques to examine ECM fungal communities
      associating with these trees. A distinctive subset of the ECM fungal community
      predominated far from plantations, indicating differences between highly invasive
      and less invasive ECM fungi. Some fungal invaders reported here have been
      detected in other locations around the world, suggesting strong invasion
      potential. Fungi that were frequently detected far from plantations are often
      found in early-successional sites in the native range, while fungi identified as
      late-successional species in the native range are rarely found far from
      plantations, suggesting a means for predicting potential fungal coinvaders. 

PMID- 25963604
TI  - An assessment of the occupational and environmental health needs in seven
      Southeastern European and West-Central Asian countries.
AB  - Eastern European and Central Asian countries are undergoing rapid socioeconomic
      and political reforms. Many old industrial facilities are either abandoned, or
      use outdated technologies that severely impact the environment. Emerging
      industries have less regulation than in developed countries and environmental and
      occupational problems seem to be increasing. Under a US National Institutes of
      Health pilot grant, we developed an interdisciplinary One Health research network
      in Southeastern Europe and West-Central Asia to identify environmental and
      occupational problems. From 2012 to 2014, this GeoHealth Hub engaged 11 academic
      centers and 16 public health institutions in eight different countries: Albania,
      Armenia, Georgia, Kazakhstan, Kyrgyzstan, Moldova, Romania, and the United States
      with a goal of strengthening environmental and occupational research and training
      capacities. Employing face-to-face interviews and large group meetings, we
      conducted an evidenced-based needs and opportunities assessment focused on
      aquatic health, food safety, and zoonotic diseases. Comprehensive reviews of the
      published literature yielded priority research areas for each of the seven
      GeoHealth Hub countries including heavy metal and pesticide contamination, tick
      borne diseases, rabies, brucellosis, and inadequate public health surveillance. 

PMID- 25963606
TI  - Overexpression of miR-21 promotes the proliferation and migration of cervical
      cancer cells via the inhibition of PTEN.
AB  - The oncogenic miR-21 has been widely recognized to promote the development and
      progression of various types of malignant tumors, but not cervical cancers. The
      aim of this study was to examine the expression of miR-21 and PTEN in cervical
      cancer specimens using quantitative PCR. The miR-21 level was then manipulated in
      the cervical cancer lines and the regulation of miR-21 on the proliferation,
      migration and invasion of cervical cancer cells was determined. Additionally, we
      determined the role of PTEN in the miR-21-regulated proliferation, migration and
      invasion of cervical cancer cells. miR-21 was upregulated in the cervical cancer
      specimens, negatively correlating with the PTEN mRNA level. Transfection of the
      miR-21 mimics was markedly promoted, whereas the miR-21 inhibitor suppressed the
      proliferation, migration and invasion of cervical cancer cells, with a
      significant inhibition of PTEN expression. In addition, the overexpression of
      PTEN markedly inhibited the proliferation and migration of the cervical cancer
      cells. The present study showed the upregulation of miR-21 in invasive cervical
      cancers, and confirmed the promotion of miR-21 with regard to the proliferation,
      migration and invasion in cervical cancer cells via inhibiting the PTEN
      expression. To the best of our knowledge, this is the first study to confirm that
      the miR-21/PTEN pathway promotes cervical cancer. 

PMID- 25963609
TI  - The societal burden of chronic pain in Japan: an internet survey.
AB  - OBJECTIVES: Chronic pain affects between 10-20 % of the population of Japan and
      several specific types of chronic pain have been found to be associated with
      worse health outcomes. The aim of the current study was to investigate the
      economic burden of chronic pain as well as the health status among Japanese
      patients. METHODS: Data from the Japan National Health and Wellness Survey
      (NHWS), a cross-sectional health survey of adults, were used (N = 30,000).
      Respondents with chronic pain (N = 785) were compared with respondents without
      chronic pain (N = 29,215) with respect to health status (using the SF-12v2), work
      productivity and activity impairment (WPAI questionnaire), and healthcare
      resource use using regression modeling, controlling for demographic and health
      history covariates. Indirect costs were calculated using wage rates and the human
      capital method. RESULTS: Back pain (72.10 %) and shoulder pain/stiffness (54.90
      %) were the most prevalent pain types. Adjusting for demographic and health
      history differences, respondents with chronic pain reported lower health status
      [mental component summary (MCS): 44.26 vs. 51.14; physical component summary
      (PCS): 44.23 vs. 47.48; both p < 0.05], greater absenteeism (4.74 vs. 2.74 %),
      presenteeism (30.19 vs. 15.19 %), overall work impairment (31.70 vs. 16.82 %),
      indirect costs (Y 1488,385 vs. Y 804,634), activity impairment (33.45 vs. 17.25
      %), physician visits (9.31 vs. 4.08), emergency room (ER) visits (0.19 vs. 0.08),
      and hospitalizations (0.71 vs. 0.34) (all p < 0.05). Nearly 60 % of respondents
      with chronic pain were untreated. The mean level of pain severity in the last
      week was 5.26 (using a 0-11 scale); being female, being elderly, having low
      income, and having multiple pain types were significantly associated with greater
      pain severity (all p < 0.05). Regular exercise was associated with lower pain
      severity (p < 0.05). CONCLUSIONS: The results suggest that chronic pain has a
      significant association in an individual's health status, work productivity,
      daily activity impairment, healthcare resource use, and economic burden in Japan.
      Along with low treatment rates, a multidisciplinary approach may lead to an
      improved quality of life and reduce the economic burden among patients with
      chronic pain in Japan.

PMID- 25963608
TI  - Analysis of mechanical failure associated with reoperation in spinal fusion to
      the sacrum in adult spinal deformity.
AB  - BACKGROUND: Long fusion to the sacrum has been demonstrated to increase the
      mechanical failure rate after adult spinal deformity (ASD) surgery, and these
      mechanical failures are the most common etiology for reoperation. The purpose of
      this study was to determine the incidence and risk factors for mechanical failure
      associated with reoperation after spinal fusion to the sacrum in ASD. METHODS:
      The study included 76 patients with ASD who underwent spinal fusion surgery
      including the sacrum at a single institution between 2005 and 2010. The inclusion
      criteria were a minimum age of 20 years and fusion of >= 5 levels. The terminal
      event was defined as either the first reoperation for mechanical failure or a
      minimum of 2 years following surgery in patients who did not undergo reoperation.
      RESULTS: The cumulative reoperation rate for mechanical failure was 37 % (n =
      28). The procedure survival rate was 79 % at 1 year and 72 % at 2 years.
      Mechanical failures consisted of proximal junctional complications in 16 patients
      and pseudarthrosis in 12 patients. Proximal junctional kyphosis (PJK) was the
      most frequent cause (n = 15), and seven patients were diagnosed with fractures at
      the UIV or one level above the UIV. Multivariate analysis identified the
      following as independent factors predicting mechanical failure: three or more
      comorbidities, smoking, and a preoperative sagittal vertical axis of >95 mm. SRS
      22r and ODI scores were lower in patients with mechanical failure. CONCLUSION:
      Overall, 37 % of the patients who underwent ASD surgery involving the sacrum
      required reoperation for mechanical failure. The most frequent form of mechanical
      failure associated with reoperation was surgical PJK. Significant risk factors
      for mechanical failure included medical comorbidities, smoking, and severe
      preoperative sagittal imbalance. Critical mechanical failure may have a negative
      influence on health status.

PMID- 25963607
TI  - Who Follows eHealth Interventions as Recommended? A Study of Participants'
      Personal Characteristics From the Experimental Arm of a Randomized Controlled
      Trial.
AB  - BACKGROUND: Computer-tailored eHealth interventions to improve health behavior
      have been demonstrated to be effective and cost-effective if they are used as
      recommended. However, different subgroups may use the Internet differently, which
      might also affect intervention use and effectiveness. To date, there is little
      research available depicting whether adherence to intervention recommendations
      differs according to personal characteristics. OBJECTIVE: The aim was to assess
      which personal characteristics are associated with using an eHealth intervention
      as recommended. METHODS: A randomized controlled trial was conducted among a
      sample of the adult Dutch population (N=1638) testing an intervention aimed at
      improving 5 healthy lifestyle behaviors: increasing fruit and vegetable
      consumption, increasing physical activity, reducing alcohol intake, and promoting
      smoking cessation. Participants were asked to participate in those specific
      online modules for which they did not meet the national guideline(s) for the
      respective behavior(s). Participants who started with fewer than the recommended
      number of modules of the intervention were defined as users who did not follow
      the intervention recommendation. RESULTS: The fewer modules recommended to
      participants, the better participants adhered to the intervention modules.
      Following the intervention recommendation increased when participants were older
      (chi(2)1=39.8, P<.001), female (chi(2)1=15.8, P<.001), unemployed (chi(2)1=7.9,
      P=.003), ill (chi(2)1=4.5, P=.02), or in a relationship (chi(2)1=7.8, P=.003). No
      significant relevant differences were found between groups with different levels
      of education, incomes, or quality of life. CONCLUSION: Our findings indicate that
      eHealth interventions were used differently by subgroups. The more frequent as
      recommended intervention use by unemployed, older, and ill participants may be an
      indication that these eHealth interventions are attractive to people with a
      greater need for health care information. Further research is necessary to make
      intervention use more attractive for people with unhealthy lifestyle patterns.

PMID- 25963610
TI  - Quadriceps tendon pie-crusting release of stiff knees in total knee arthroplasty.
AB  - BACKGROUND: Traditional treatments for stiff knees, such as quadriceps snip and V
      Y quadricepsplasty, require extensive soft tissue exposure and lead to recurrent
      poor arc of motion and a permanent extensor lag. In this study, we evaluated the
      effect of the quadriceps tendon pie-crusting release for treating limited knee
      flexion in total knee arthroplasty (TKA) and compared the outcomes of two
      surgical approaches. METHODS: Sixteen knees with severe osteoarthritis were
      treated with TKA using either a midvastus (eight knees) or parapatellar (eight
      knees) approach. Quadriceps tendon pie-crusting release was performed after
      fixation of the knee prosthesis. Maximum knee flexion, Knee Society Score (KSS),
      and quadriceps strength were recorded and compared between the two surgical
      approach groups at different time points. RESULTS: The average maximum flexion
      angle of the knee increased from 40.6 +/- 11.8 preoperatively to 63.1 +/- 8.4
      after fixation of the knee prosthesis in the midvastus group and from 38.8 +/-
      10.3 to 65.6 +/- 9.0 in the parapatellar group. TKA did not lead to adequate
      correction of extension contracture in these stiff knees. The quadriceps tendon
      pie-crusting release further improved knee flexion by 35.0 +/- 4.6 and 25.6 +/-
      4.2 in the midvastus and parapatellar groups, respectively (p < 0.001). Patients
      in the midvastus group had higher mean KSS (88.2 +/- 2.4) compared with the
      parapatellar group (84.1 +/- 3.1) at the last follow-up (p = 0.048). CONCLUSIONS:
      The quadriceps tendon pie-crusting release technique was an effective procedure
      for improving knee flexion in cases of stiff knee. The midvastus approach
      maintained the integrity of the extensor mechanism and resulted in better
      outcomes than the parapatellar approach.

PMID- 25963611
TI  - Prevalence of radiological femoroacetabular impingement in Japanese hip joints:
      detailed investigation with computed tomography.
AB  - BACKGROUND: Femoroacetabular impingement (FAI) has been highlighted as a new
      etiology for osteoarthritis of the hip, and its prevalence has been reported in
      the past decade. In the present study, we performed a detailed investigation of
      the anatomical parameters related to FAI and calculated the prevalence of FAI
      related findings in asymptomatic Japanese hip joints using computed tomography.
      METHODS: We evaluated high-resolution reconstructed multislice computed
      tomography images in patients who had undergone computed tomography imaging in
      our institution for conditions unrelated to hip disorders. The examined
      parameters were as follows: center-edge (CE) angle; acetabular index; acetabular
      anteversion (five slices in the axial plane); and asphericity angle of the
      femoral head (AAFH) (six slices in multiple radial planes). The AAFH in the
      oblique axial slice through the center of the femoral neck is the so-called alpha
      angle. We then examined the accurate prevalence of FAI-related findings in Japan.
      RESULTS: We investigated a total of 103 hips. The mean age of the subjects was
      59.4 years. The mean CE angle was 31.1 degrees  and the mean acetabular index was
      7.0 degrees . The mean acetabular anteversion was 20.3 degrees  at the level of
      the hip center, and decreased as the slice level neared the superior margin of
      the femoral head. The mean AAFH ranged from 40.6 degrees  to 49.2 degrees  in the
      radial planes. The AAFH was largest at 60 degrees  rotated slice from the oblique
      axial slice through the center of the femoral neck. The prevalence of FAI-related
      findings in these Japanese hip joints was assessed as follows. An AAFH of >50
      degrees  in any slice was detected in 51.5 % of the hips, and acetabular
      anteversion was negative for all images in 16.5 % of the hips, meaning that a
      total of 56.3 % of the images met the criteria for radiological FAI. CONCLUSIONS:
      With consideration of our results, we emphasize that "anatomical or radiological
      FAI" is not uncommon in Japanese hips. Therefore, the diagnosis of FAI should be
      performed with the clinical findings taken into account.

PMID- 25963612
TI  - The complications of awake tracheal intubation.

PMID- 25963613
TI  - Prospective assessment of autism traits in children exposed to antiepileptic
      drugs during pregnancy.
AB  - PURPOSE: The association between autism spectrum disorders (ASDs) and prenatal
      anticonvulsant exposure is increasingly investigated, but comprehensive, blinded
      assessment using a validated instrument for autism within a well-characterized
      prospective cohort has not been conducted. Thus, existing studies may represent
      an underestimate of the true risk. Herein we present a prospective cohort study
      in children exposed to anticonvulsants during pregnancy, with all assessments
      conducted by examiners who were blinded to drug-exposure status. METHODS:
      Participants were 105 Australian children aged 6-8 years who were recruited via
      the Australian Pregnancy Register for Women on Antiepileptic Medication. Maternal
      epilepsy, pregnancy, and medical history data were obtained prospectively. Autism
      traits were assessed using the Childhood Autism Rating Scale (CARS). RESULTS:
      Eleven children (10.5%) had elevated CARS scores. Two were exposed to valproate
      monotherapy (2/26; 7.7%), two to carbamazepine monotherapy (2/34; 5.9%), and
      seven to valproate in polytherapy (7/15; 46.7%). Linear regression analysis
      showed that the mean valproate dose during pregnancy was a significant predictor
      of CARS scores after controlling for polytherapy, mean carbamazepine dose, folic
      acid use, seizures during pregnancy, tobacco and marijuana use, maternal
      intelligence quotient (IQ), and socioeconomic status. First trimester folic acid
      supplementation and marijuana use were also significant predictors of CARS
      scores. SIGNIFICANCE: Using direct assessment of children in our prospective
      study, we found an elevated rate of autism traits across the sample. The most
      important determinant of association with autistic traits was higher doses of
      sodium valproate exposure. The use of valproate in women who may become pregnant
      is now generally avoided; however, there are insufficient data regarding the risk
      of ASD with low-dose valproate. If this risk is no greater than with other
      antiepileptic drugs (AED)s, it may enable women with genetic generalized epilepsy
      to retain optimal seizure control as well as minimize harm to their unborn child.

PMID- 25963614
TI  - The Moral Virtue of Authenticity: How Inauthenticity Produces Feelings of
      Immorality and Impurity.
AB  - The five experiments reported here demonstrate that authenticity is directly
      linked to morality. We found that experiencing inauthenticity, compared with
      authenticity, consistently led participants to feel more immoral and impure. This
      link from inauthenticity to feeling immoral produced an increased desire among
      participants to cleanse themselves and to engage in moral compensation by
      behaving prosocially. We established the role that impurity played in these
      effects through mediation and moderation. We found that inauthenticity-induced
      cleansing and compensatory helping were driven by heightened feelings of impurity
      rather than by the psychological discomfort of dissonance. Similarly, physically
      cleansing oneself eliminated the relationship between inauthenticity and
      prosocial compensation. Finally, we obtained additional evidence for discriminant
      validity: The observed effects on desire for cleansing were not driven by general
      negative experiences (i.e., failing a test) but were unique to experiences of
      inauthenticity. Our results establish that authenticity is a moral state--that
      being true to thine own self is experienced as a form of virtue.

PMID- 25963615
TI  - Visualizing Trumps Vision in Training Attention.
AB  - Mental imagery can have powerful training effects on behavior, but how this
      occurs is not well understood. Here we show that even a single instance of mental
      imagery can improve attentional selection of a target more effectively than
      actually practicing visual search. By recording subjects' brain activity, we
      found that these imagery-induced training effects were due to perceptual
      attention being more effectively focused on targets following imagined training.
      Next, we examined the downside of this potent training by changing the target
      after several trials of training attention with imagery and found that imagined
      search resulted in more potent interference than actual practice following these
      target changes. Finally, we found that proactive interference from task
      irrelevant elements in the visual displays appears to underlie the superiority of
      imagined training relative to actual practice. Our findings demonstrate that
      visual attention mechanisms can be effectively trained to select target objects
      in the absence of visual input, and this results in more effective control of
      attention than practicing the task itself. 

PMID- 25963616
TI  - It's All in the Family: Brain Asymmetry and Syntactic Processing of Word Class.
AB  - Although left-hemisphere (LH) specialization for language is often viewed as a
      key example of functional lateralization, there is increasing evidence that the
      right hemisphere (RH) can also extract meaning from words and sentences. However,
      the right hemisphere's ability to appreciate syntactic aspects of language
      remains poorly understood. In the current study, we used separable, functionally
      well-characterized electrophysiological indices of lexico-semantic and syntactic
      processes to demonstrate RH sensitivity to syntactic violations among right
      handers with a strong manual preference. Critically, however, the nature of this
      RH sensitivity to structural information was modulated by a genetically
      determined factor--familial sinistrality. The right hemisphere in right-handers
      without left-handed family members processed syntactic violations via the words'
      accompanying lexico-semantic unexpectedness. In contrast, the right hemisphere in
      right-handers with left-handed family members could process syntactic information
      in a manner qualitatively similar to that of the left hemisphere.

PMID- 25963617
TI  - Exploring proteome-wide occurrence of clusters of charged residues in eukaryotes.
AB  - Clusters of charged residues are one of the key features of protein primary
      structure since they have been associated to important functions of proteins.
      Here, we present a proteome wide scan for the occurrence of Charge Clusters in
      Protein sequences using a new search tool (FCCP) based on a score-based
      methodology. The FCCP was run to search charge clusters in seven eukaryotic
      proteomes: Arabidopsis thaliana, Caenorhabditis elegans, Danio rerio, Drosophila
      melanogaster, Homo sapiens, Mus musculus, and Saccharomyces cerevisiae. We found
      that negative charge clusters (NCCs) are three to four times more frequent than
      positive charge clusters (PCCs). The Drosophila proteome is on average the most
      charged, whereas the human proteome is the least charged. Only 3 to 8% of the
      studied protein sequences have negative charge clusters, while 1.6 to 3% having
      PCCs and only 0.07 to 0.6% have both types of clusters. NCCs are localized
      predominantly in the N-terminal and C-terminal domains, while PCCs tend to be
      localized within the functional domains of the protein sequences. Furthermore,
      the gene ontology classification revealed that the protein sequences with
      negative and PCCs are mainly binding proteins.

PMID- 25963619
TI  - A case of human infection with Anisakis simplex in Taiwan.

PMID- 25963618
TI  - Genetically integrated traits and rugged adaptive landscapes in digital
      organisms.
AB  - BACKGROUND: When overlapping sets of genes encode multiple traits, those traits
      may not be able to evolve independently, resulting in constraints on adaptation.
      We examined the evolution of genetically integrated traits in digital organisms
      self-replicating computer programs that mutate, compete, adapt, and evolve in a
      virtual world. We assessed whether overlap in the encoding of two traits - here,
      the ability to perform different logic functions - constrained adaptation. We
      also examined whether strong opposing selection could separate otherwise
      entangled traits, allowing them to be independently optimized. RESULTS:
      Correlated responses were often asymmetric. That is, selection to increase one
      function produced a correlated response in the other function, while selection to
      increase the second function caused a complete loss of the ability to perform the
      first function. Nevertheless, most pairs of genetically integrated traits could
      be successfully disentangled when opposing selection was applied to break them
      apart. In an interesting exception to this pattern, the logic function AND
      evolved counter to its optimum in some populations owing to selection on the EQU
      function. Moreover, the EQU function showed the strongest response to selection
      only after it was disentangled from AND, such that the ability to perform AND was
      lost. Subsequent analyses indicated that selection against AND had altered the
      local adaptive landscape such that populations could cross what would otherwise
      have been an adaptive valley and thereby reach a higher fitness peak.
      CONCLUSIONS: Correlated responses to selection can sometimes constrain
      adaptation. However, in our study, even strongly overlapping genes were usually
      insufficient to impose long-lasting constraints, given the input of new mutations
      that fueled selective responses. We also showed that detailed information about
      the adaptive landscape was useful for predicting the outcome of selection on
      correlated traits. Finally, our results illustrate the richness of evolutionary
      dynamics in digital systems and highlight their utility for studying processes
      thought to be important in biological systems, but which are difficult to
      investigate in those systems.

PMID- 25963620
TI  - A trapping-evacuation technique for giant carotid-ophthalmic segment aneurysm
      clipping in a hybrid operating theater.
AB  - It is essential to collapse giant carotid-ophthalmic (OA) segment aneurysms for
      successful microsurgical clipping. We present a trapping-evacuation technique
      utilising hybrid operating theater capabilities to soften OA aneurysms. The
      patients were prepared for both microsurgical and endovascular procedures. After
      the majority of the aneurysm was exposed, a balloon was placed at the orifice of
      the aneurysm to fully block the blood flow. When the balloon was inflated, blood
      was evacuated from the aneurysm sac to eliminate the space occupying effect.
      Subsequently, the aneurysm neck was clearly exposed which greatly facilitated
      clip placement. A control angiogram was obtained prior to closing the wound to
      ensure complete aneurysm obliteration. After the establishment of a hybrid
      operating theater in our hospital, two aneurysms were successfully clipped using
      this technique. Although postoperative complications occurred in both patients,
      none of the events were related to the endovascular procedure or the trapping
      evacuation technique. As a well-organized procedure designed for use in a hybrid
      operating theater, the current trapping-evacuation technique is an option for the
      surgical clipping of giant OA aneurysms. 

PMID- 25963621
TI  - Personalizing Biomaterials for Precision Nanomedicine Considering the Local
      Tissue Microenvironment.
AB  - New advances in (nano)biomaterial design coupled with the detailed study of
      tissue-biomaterial interactions can open a new chapter in personalized medicine,
      where biomaterials are chosen and designed to match specific tissue types and
      disease states. The notion of a "one size fits all" biomaterial no longer exists,
      as growing evidence points to the value of customizing material design to enhance
      (pre)clinical performance. The complex microenvironment in vivo at different
      tissue sites exhibits diverse cell types, tissue chemistry, tissue morphology,
      and mechanical stresses that are further altered by local pathology. This complex
      and dynamic environment may alter the implanted material's properties and in turn
      affect its in vivo performance. It is crucial, therefore, to carefully study
      tissue context and optimize biomaterials considering the implantation conditions.
      This practice would enable attaining predictable material performance and enhance
      clinical outcomes. 

PMID- 25963623
TI  - Expression and function analysis of two naturally truncated MyD88 variants in the
      Pacific oyster Crassostrea gigas.
AB  - Myeloid differentiation factor 88 (MyD88) is the classic signaling adaptor that
      mediates Toll/interleukin-1 receptor (TIR/IL-1R) dependent activation of nuclear
      factor-kappa B (NF-kappaB). In this study, two naturally truncated MyD88 members
      were identified from the Pacific oyster (Crassostrea gigas), namely CgMyD88-T1
      and CgMyD88-T2. The full-length cDNA of CgMyD88-T1, CgMyD88-T2 are 976 bp and
      1038 bp in length, containing an ORF of 552 bp and 555 bp, respectively. The two
      ORF encode a putative protein of 183 and 184 amino acids, respectively, with a
      calculated molecular weight of about 21 and 22 kDa. When compared to complete
      MyD88 paralogues, we found that both CgMyD88-T1 and CgMyD88-T2 contain only TIR
      domain but lack DD (Death Domain), which share 90.8% of similarity and 71.7% of
      identity with each other. Phylogenetic tree demonstrated that CgMyD88-T1 and
      CgMyD88-T2 clustered together and belonged to mollusk branch. Meanwhile, genomic
      arrangement analysis displayed that the two truncated MyD88s were distributed in
      tandem in one scaffold, revealing that they may originate from one truncated
      MyD88 ancestor recently. Expression profile showed that both of CgMyD88 variants
      were ubiquitously expressed in all tested tissues with highest expression in the
      gills and hemocytes, respectively. Both truncated CgMyD88 mRNAs were
      significantly up-regulated in hemocytes under HKLM (heat-killed Listeria
      monocytogenes) and HKVA (heat-killed Vibrio alginolyticus) challenge. Moreover,
      either CgMyD88-T1 or CgMyD88-T2 were able to inhibit MyD88 activated Rel/NF
      kappaB activity in HEK293 cell, demonstrating their negative role in regulating
      MyD88-mediated immune signaling.

PMID- 25963624
TI  - Effectiveness of lenalidomide in a patient with refractory anemia with ring
      sideroblasts and thrombocytosis with JAK2 (V617F) mutation.

PMID- 25963625
TI  - Outcomes of transcatheter aortic valve replacement in patients with chronic liver
      disease.
AB  - OBJECTIVE: Transcatheter aortic valve replacement (TAVR) has emerged as an
      alternative to high-risk surgery in patients with comorbid conditions. The role
      of TAVR in patients with liver disease has not been examined. METHODS: We
      examined the procedural and intermediate to long-term follow-up outcomes of
      patients with severe symptomatic aortic valve stenosis and chronic liver disease,
      identified by liver biopsy or from a combination of clinical findings. All
      patients were treated with balloon-expandable transfemoral (TF) or transapical
      (TA) TAVR between November 2007 and February 2014. RESULTS: A total of 17 of 706
      (2.41%) patients treated at our institution with TF [n=14] or TA [n=3] TAVR had
      chronic liver disease (mean age 77.65+/-9.06 years, 7 women, mean STS score 8.37,
      mean Charlson score 5.00, mean MELD score 11.35, Child-Turcotte-Pugh (CTP) Class
      A [n=11], B [n=6], C [n=0], biopsy proven liver disease [n=5]). Median follow-up
      was 466 days (range=12-1,403 days). The mean post-procedure length of hospital
      stay was 5.88+/-3.08 days. Procedural success was achieved in all cases. In
      hospital mortality was 5.88% and 90-day mortality was 17.65%. Safety and efficacy
      endpoints as defined by the valve academic research consortium (VARC) were
      significant for one perioperative death from a proximate cardiac cause (post
      operative day 14), one death after hospital discharge of unknown cause (post
      operative day 12), two late deaths from non-cardiac causes (post-operative days
      50 and 487, respectively), and one late death of unknown cause (post-operative
      day 1,005). There were no life-threatening or major bleeding complications. One
      patient had an MI, one had a transient ischemic attack, four had transient, Stage
      I, acute kidney injury and one had transient, Stage II, acute kidney injury.
      CONCLUSION: TF and TA TAVR are feasible methods for treating aortic stenosis in
      patients with chronic liver disease. In patients with mild to moderate chronic
      liver disease there are acceptable rates of early and late complications,
      however, outcomes in patients with advanced liver disease (MELD>20 or CTP class
      C) warrant further study.

PMID- 25963627
TI  - Effective Strategies to Spread Redesigning Care Processes Among Healthcare Teams.
AB  - PURPOSE: The purpose of this study was to describe how spread strategies
      facilitate the successful implementation of the Transforming Care at the Bedside
      (TCAB) program and their impact on healthcare workers and patients in a major
      Canadian healthcare organization. DESIGN: This study used a qualitative and
      descriptive design with focus groups and individual interviews held in May 2014.
      Participants included managers and healthcare providers from eight TCAB units in
      a university health center in Quebec, Canada. The sample was composed of 43
      individuals. METHODS: The data were analyzed using NVivo according to the method
      proposed by Miles and Huberman. FINDINGS: The first two themes that emerged from
      the analysis are related to context (organizational transition requiring many
      changes) and spread strategies for the TCAB program (senior management support,
      release time and facilitation, rotation of team members, learning from previous
      TCAB teams, and engaging patients). The last theme that emerged from the analysis
      is the impact on healthcare professionals (providing front-line staff and
      managers with the training they need to make changes, team leadership, and
      increasing receptivity to hearing patients' and families' needs and requests).
      CONCLUSIONS: This study describes the perspectives of managers and team members
      to provide a better understanding of how spread strategies can facilitate the
      successful implementation of the TCAB program in a Canadian healthcare
      organization. CLINICAL RELEVANCE: Spread strategies facilitate the implementation
      of changes to improve the quality and safety of care provided to patients.

PMID- 25963626
TI  - CD11c-mediated deletion of Flip promotes autoreactivity and inflammatory
      arthritis.
AB  - Dendritic cells (DCs) are critical for immune homeostasis. To target DCs, we
      generated a mouse line with Flip deficiency in cells that express cre under the
      CD11c promoter (CD11c-Flip-KO). CD11c-Flip-KO mice spontaneously develop erosive,
      inflammatory arthritis, resembling rheumatoid arthritis, which is dramatically
      reduced when these mice are crossed with Rag(-/-) mice. The CD8alpha(+) DC subset
      is significantly reduced, along with alterations in NK cells and macrophages.
      Autoreactive CD4(+) T cells and autoantibodies specific for joint tissue are
      present, and arthritis severity correlates with the number of autoreactive CD4(+)
      T cells and plasmablasts in the joint-draining lymph nodes. Reduced T regulatory
      cells (Tregs) inversely correlate with arthritis severity, and the transfer of
      Tregs ameliorates arthritis. This KO line identifies a model that will permit in
      depth interrogation of the pathogenesis of rheumatoid arthritis, including the
      role of CD8alpha(+) DCs and other cells of the immune system. 

PMID- 25963628
TI  - Radiation dose-rate effects on gene expression for human biodosimetry.
AB  - BACKGROUND: The effects of dose-rate and its implications on radiation
      biodosimetry methods are not well studied in the context of large-scale
      radiological scenarios. There are significant health risks to individuals exposed
      to an acute dose, but a realistic scenario would include exposure to both high
      and low dose-rates, from both external and internal radioactivity. It is
      important therefore, to understand the biological response to prolonged exposure;
      and further, discover biomarkers that can be used to estimate damage from low
      dose rate exposures and propose appropriate clinical treatment. METHODS: We
      irradiated human whole blood ex vivo to three doses, 0.56 Gy, 2.23 Gy and 4.45
      Gy, using two dose rates: acute, 1.03 Gy/min and a low dose-rate, 3.1 mGy/min.
      After 24 h, we isolated RNA from blood cells and these were hybridized to Agilent
      Whole Human genome microarrays. We validated the microarray results using qRT
      PCR. RESULTS: Microarray results showed that there were 454 significantly
      differentially expressed genes after prolonged exposure to all doses. After acute
      exposure, 598 genes were differentially expressed in response to all doses. Gene
      ontology terms enriched in both sets of genes were related to immune processes
      and B-cell mediated immunity. Genes responding to acute exposure were also
      enriched in functions related to natural killer cell activation and cell-to-cell
      signaling. As expected, the p53 pathway was found to be significantly enriched at
      all doses and by both dose-rates of radiation. A support vectors machine
      classifier was able to distinguish between dose-rates with 100 % accuracy using
      leave-one-out cross-validation. CONCLUSIONS: In this study we found that low dose
      rate exposure can result in distinctive gene expression patterns compared with
      acute exposures. We were able to successfully distinguish low dose-rate exposed
      samples from acute dose exposed samples at 24 h, using a gene expression-based
      classifier. These genes are candidates for further testing as markers to classify
      exposure based on dose-rate.

PMID- 25963629
TI  - A Novel Segment Classification for Multifocal and Multicentric Breast Cancer to
      Facilitate Breast-Conservation Treatment.
AB  - Breast conservation treatment (BCT) is an appropriate alternative to mastectomy
      for the treatment of unifocal breast cancer. Multifocal and multicentric breast
      cancers (MFMCBC) challenge conventional indications for BCT and are often treated
      with mastectomy. Following progress in treatment strategies for unifocal tumors,
      there was a movement to evaluate the use of BCT for MFMCBC. Now a growing body of
      evidence from retrospective data has emerged, demonstrating acceptable local
      control and overall survival rates with BCT for MFMCBC. Prospective studies are
      needed to confirm these findings. One of the possible barriers to such trials is
      the absence of a standardized classification and nomenclature for MFMCBC at this
      point in time. A novel segment classification is presented in this article in an
      endeavor to overcome this deficiency and allow future work on this issue. 

PMID- 25963630
TI  - Alternative stable states in a stage-structured consumer-resource biomass model
      with niche shift and seasonal reproduction.
AB  - We formulate and analyze a stage-structured consumer-resource biomass model, in
      which consumers reproduce in a pulsed event at the beginning of a growing season
      and furthermore go through a niche shift during their life history. We show that
      the resulting semi-discrete model can exhibit two stable states that can be
      characterized as a development-controlled state and a reproduction-controlled
      state. Varying resource availabilities and varying the extent of the niche shift
      determines whether juveniles or adults are more limited by their resource(s) and
      can lead to switches between the alternative stable states. Furthermore, we
      quantify the persistence of the consumer population and the occurrence of the two
      alternative stable states as a function of resource availabilities and extent of
      the niche shift. All the results show that irrespective of the type of
      reproduction of the consumers (continuous or seasonal), the stage-structured
      model will exhibit alternative stable states as long as development of the
      juvenile stage and reproduction of the adult stage are both resource-dependent. 

PMID- 25963631
TI  - Modeling population responses of Chinook and coho salmon to suspended sediment
      using a life history approach.
AB  - This study develops a quantitative framework for estimating the effects of
      extreme suspended-sediment events (SSC>25 mg L(-1)) on virtual populations of
      Chinook (Oncorhynchus tshawytscha) and coho (O. kisutch) salmon in a coastal
      watershed of British Columbia, Canada. We used a life history model coupled with
      a dose-response model to evaluate the populations' responses to a set of
      simulated suspended sediments scenarios. Our results indicate that a linear
      increase in SSC produces non-linear declining trajectories in both Chinook and
      coho populations, but this decline was more evident for Chinook salmon despite
      their shorter fresh-water residence. The model presented here can provide
      insights into SSC impacts on population responses of salmonids and potentially
      assist resource managers when planning conservation or remediation strategies. 

PMID- 25963633
TI  - Markers for the population genetics studies of Triatoma sordida (Hemiptera:
      Reduviidae).
AB  - BACKGROUND: Triatoma sordida, a vector of Trypanosoma cruzi, is native of Brazil,
      Bolivia, Paraguay, Argentina, and Uruguay, and occurs primarily in peridomiciles.
      Currently, it is the species most frequently captured by the Chagas Disease
      Control Program in Brazil. For this reason, population genetic studies attract
      great interest, as they can provide further information about the dispersal and
      household invasion processes of this species. In the absence of suitable markers,
      the objective of this study was to test the cross amplification of microsatellite
      primers. FINDINGS: 23 primers were tested for microsatellite loci already
      described for other species of the genus Triatoma sp. Forty four specimens of T.
      sordida captured in the north of Minas Gerais were used to validate the use of
      standardized loci for population genetic analyses. It was possible to amplify 10
      of the 23 loci tested for T. sordida. CONCLUSIONS: This is the first study that
      provides 10 microsatellite markers for population analysis of this triatomine
      species. Cross-amplification of primers can be used among other phylogenetically
      related species whose loci are already available for study.

PMID- 25963634
TI  - Electroacupuncture inhibits weight gain in diet-induced obese rats by activating
      hypothalamic LKB1-AMPK signaling.
AB  - BACKGROUND: Electroacupuncture (EA) is reported to be an effective treatment for
      obesity, but its mechanism is unclear. This study aimed to investigate the
      relationship between hypothalamic LKB1-AMPK-ACC signaling and EA. METHODS: Fifty
      male Sprague-Dawley rats were divided into two groups fed either chow (chow-fed
      group) or high-fat diet (HF group). After 4 weeks of feeding, obese rats in the
      HF group (defined as weighing 20% or more than rats in the chow-fed group) were
      randomly allocated into an EA or Diet-induced obesity (DIO) group. The EA group
      was given EA on bilateral ST25-ST36 for 4 weeks, while the DIO group received no
      further intervention. Body weight of the chow-fed, DIO, and EA groups were
      measured weekly. mRNA and protein levels of the hypothalamic LKB1-AMPK-ACC
      signaling pathway were detected using real-time (RT)-PCR and western blot,
      respectively. RESULTS: After 4 weeks of EA treatment, the weight growth trend of
      rats in the EA group was inhibited compared with those in the DIO group. RT-PCR
      and western blotting showed that EA upregulated the transcription of Adenosine 5'
      monophosphate-activated protein kinase alpha2 (AMPKalpha2), promoted protein
      expression of Liver kinase B1 (LKB1) and AMPKalpha1, and inhibited acetyl-CoA
      carboxylase (ACC) protein expression in the hypothalamus. CONCLUSIONS: This study
      suggests that hypothalamic LKB1-AMPK-ACC signaling plays an important role in EA
      treatment for obesity.

PMID- 25963635
TI  - Increasing bystander CPR: potential of a one question telecommunicator
      identification algorithm.
AB  - OBJECTIVES: Telecommunicators use a two-question algorithm to identify cardiac
      arrest: Is the individual conscious? Is the individual breathing normally?
      Although this approach increases arrest identification and consequently bystander
      CPR, the strategy does not identify all arrests and requires time to complete. We
      evaluated the implications of a one-question strategy that inquired only about
      consciousness. METHODS: We undertook a 3-month observational study of consecutive
      cases identified as unconscious by the telecommunicator prior to EMS arrival who
      were not receiving bystander CPR. We evaluated the extent that a one-question
      strategy could increase arrest identification and reduce the identification
      interval; and the trade-off whereby additional persons without arrest could
      potentially receive CPR. RESULTS: Among 679 eligible cases, 20% (n = 135) were in
      arrest and 80% (n = 544) were not in arrest. The two-question algorithm
      identified 90% (121/135) as true arrest. Of the 135 in arrest, 70% (n = 95)
      received compressions. The median interval from call to arrest identification was
      72 seconds, with a median of 14 seconds for the breathing normally question.
      Using the two-question algorithm, telecommunicators incorrectly classified 30% (n
      = 164/544) of non-arrests as arrest. Bystanders proceeded to compressions in 16%
      (n = 85/544) of persons not in arrest. A one-question approach that inquired only
      about consciousness could potentially increase the arrest identification by 10%
      (14/135) and reduce the interval to compressions by a median of 14 seconds;
      however the strategy would potentially triple the number of non-arrest cases (544
      versus 164) eligible for CPR instructions. CONCLUSION: A single-question arrest
      identification algorithm may not achieve a favorable balance of risk and benefit.

PMID- 25963637
TI  - Laparoscopy decreases the laparotomy rate for hemodynamically stable patients
      with blunt hollow viscus and mesenteric injuries.
AB  - BACKGROUND: The aim of this study was to evaluate the effect of laparoscopy on
      patients with blunt hollow viscus and mesenteric injuries (BHVMIs). METHODS:
      Hemodynamically stable patients with BHVMIs were diagnosed using computed
      tomography and serial examinations. Patients admitted from July 1, 1999 to June
      30, 2006 underwent exploratory laparotomy (group A), and those admitted from
      January 1, 2007 to December 31, 2013 received laparoscopy (group B). RESULTS:
      There were 62 patients in group A, and 59 patients in group B. There were no
      significant differences in demographic characteristics, injury severity score,
      and injuries requiring surgical intervention between the groups (all, P > .05).
      Patients in group B had a shorter hospital stay (mean 11.0 vs 17.6 days, P <
      .001) and lower wound infection rate (mean 5.1% vs 16.1%, P = .049). The
      conversion rate of laparoscopy to laparotomy in group B was 8.5%, compared with a
      100% laparotomy rate in group A (P < .001). There was no difference in the
      complication rate between groups. CONCLUSION: Laparoscopy is feasible and safe
      for hemodynamically stable patients with BHVMIs.

PMID- 25963636
TI  - Death-associated protein kinase: A molecule with functional antagonistic duality
      and a potential role in inflammatory bowel disease (Review).
AB  - The cytoskeleton-associated serine/threonine kinase death-associated protein
      kinase (DAPK) has been described as a cancer gene chameleon with functional
      antagonistic duality in a cell type and context specific manner. The broad range
      of interaction partners and substrates link DAPK to inflammatory processes
      especially in the gut. Herein we summarize our knowledge on the role of DAPK in
      different cell types that play a role under inflammatory conditions in the gut.
      Besides some promising experimental data suggesting DAPK as an interesting drug
      target in inflammatory bowel disease there are many open questions regarding
      direct evidence for a role of DAPK in intestinal inflammation. 

PMID- 25963638
TI  - Does ground glass opacity-dominant feature have a prognostic significance even in
      clinical T2aN0M0 lung adenocarcinoma?
AB  - INTRODUCTION: Recent studies have demonstrated that ground glass opacity (GGO)
      dominant tumors correspond to pathologically low-grade adenocarcinomas and that
      patients with resected tumors have an excellent prognosis. However, almost all of
      those studies were limited to tumors measuring <=3.0cm. The purpose of this study
      was to characterize lung adenocarcinomas >3.0cm in diameter with GGO-dominant
      features and evaluate the prognosis of patients with such tumors. METHODS: One
      hundred and thirteen patients with cT2aN0M0 lung adenocarcinoma underwent
      surgical resection between 2005 and 2011. Twenty-five had tumors with a >=50% GGO
      component (GGO-dominant group) and the remaining had solid-dominant tumors (Solid
      dominant group). The clinicopathological findings and prognosis of the two groups
      were evaluated. RESULTS: The tumors in the GGO-dominant group rarely exhibited
      pathological invasiveness, such as lymphatic (n=1), vascular (n=0) and pleural
      invasion (n=5) or lymph node metastasis (n=0). On the other hand, the tumors in
      the solid-dominant group frequently exhibited pathological invasiveness,
      including lymphatic (n=26), vascular (n=16) and plural invasion (n=52) and lymph
      node metastasis (n=18). There were significant differences in all of the
      characteristics between the two groups (lymphatic; p=0.0026, vascular; p=0.0214,
      and pleural invasion; p=0.0004, and lymph node metastases; p=0.0086,
      respectively). In the GGO-dominant group, 24 patients were alive without
      recurrence, while the remaining died of another cancer. Recurrence occurred in 34
      patients in the solid-dominant group, and 16 died of the disease. The 5-year
      survival rate was 96% in the GGO-dominant group, compared to 71% in the solid
      dominant group (p=0.0120). CONCLUSIONS: In the GGO-dominant group, the malignant
      potential was low and the patients had a favorable prognosis after surgery,
      similar to the patients with GGO-dominant tumors diagnosed as cT1a-bN0M0.

PMID- 25963639
TI  - [Management of highly contagious, life-threatening infectious diseases in
      Germany].
AB  - Highly contagious, life-threatening infectious diseases are extremely rare in
      Germany. It was estimated that Germany experiences approximately one such patient
      per year, but records since the year 2000 demonstrate that this has not been the
      case (six cases). Even during the current Ebola outbreak in West Africa, Germany
      is not experiencing patients-apart from those referred to by international
      organisations. However, it is necessary to establish and maintain specialised
      treatment centres for patients with highly contagious, life-threatening diseases.
      Highly contagious, life-threatening diseases are rare and neglected diseases, yet
      they can have devastating effects on individual patients, societies and entire
      economies. A dedicated expert group was formed at the German Robert Koch
      Institute (STAKOB) to network and synthesise the different centres of competence
      and treatment. This group prepares recommendations that encompass the early
      detection and treatment of patients to infectious disease management to mitigate
      the implications on societies and interrupt the chain of infections to safeguard
      the integrity of public health in Germany. 

PMID- 25963640
TI  - [General procedures in response to suspected attacks with highly contagious and
      pathogenic agents].
AB  - The discovery of undefined powders that are content of letters or parcels with or
      without threats in writing addressed to institutions, groups or persons, often
      raises the suspicion of an attack involving biological agents such as anthrax.
      Subsequent investigations and analyses by local authorities often aim at
      excluding anthrax or anthrax spores. Suspicion and actions are then mistakenly
      justified by referring to the 2001 anthrax letter attacks in the USA, which now
      lie more than 10 years in the past. In Germany to date there has never been a
      terrorist attack involving dangerous biological agents, neither in letters nor in
      any other possible form. In addition, it cannot be assumed that anthrax bacteria
      or spores will be used again in a bioterrorist event. In the case of a valid
      suspicion of a threatening letter, neither analyses to exclude only a certain
      group of substances (e.g. biological, chemical or radiological) nor analyses to
      exclude only one biological agent (e.g. anthrax) in particular would provide
      sufficient information for decision makers to conduct further actions in coping
      with the given situation. Moreover, a sequence of procedures such as
      consultation, exclusion, and analyses should be followed in order to
      systematically exclude all relevant threats. Therefore, and in respect to the
      current CBRNE threat assessment for Germany, the following article provides
      recommendations of actions to be taken for coping with a valid suspicion of an
      intentional release of biological agents utilizing powder letters as an example. 

PMID- 25963641
TI  - [Ebola virus disease in West Africa and Germany : clinical presentation,
      management and practical experience with medevacuated patients in Germany].
AB  - Ebolaviruses are the causative pathogens of a severe form of viral haemorrhagic
      fever with cytokine induced shock and multi-organ failure and a high case
      fatality rate in humans (50-90 %, more than 70 % in the beginning of the current
      outbreak), designated Ebola haemorrhagic fever or Ebola virus disease (EVD).
      Ebola is endemic in regions of Central and West Africa. Ebolavirus Zaire (EBOV)
      is the most aggressive Ebola virus species and is causing the current epidemic.
      Currently, beginning in late 2013, an unprecedented epidemic with several
      thousand cases and deaths (as per WHO report 24.12.2014: 19,497 documented cases,
      7588 death, 2352 cases in past 3 weeks) is unfolding in Guinea, Liberia and
      Sierra Leone, and spreading to other countries in Africa, Europe and the USA,
      where isolated cases have occurred. Ebola transmission occurs exclusively through
      direct contact with body fluids through mucosal surfaces, skin abrasions, or by
      parenteral introduction-an aerolised transmission has not been reported so far.
      Infections in healthcare personnel have not only occurred after needle stick
      injuries but also after unsafe doffing procedures of personal protection
      equipment (PPE). The protection of healthcare personnel caring for Ebola
      patients, therefore, requires that high standards in the use of PPE are
      mandatory. In high-income countries the management and treatment of EVD patients
      in specialized centres is recommended. Using negative pressure rooms and positive
      pressure suits may provide additional safety. Due to the high degree of training
      and monitoring needed to prevent occupational risks, treatment of EVD patients in
      non-specialized hospitals should not take place. 

PMID- 25963642
TI  - [Transcultural prevention of alcohol-related disorders : effects of a culture-
      and migration-sensitive approach in elderly migrants with respect to attitudes
      and behavior: a cluster randomized controlled trial].
AB  - BACKGROUND: For migrants who are older than 50, alcohol frequently becomes a
      problem. Simultaneously alcohol-related prevention measures only reach this group
      insufficiently. Therefore, a transcultural concept for preventing alcohol-related
      disorders in elderly (>= 45 years) migrants has been developed. METHOD: The
      transcultural concept, which consisted of a prevention event as well as a
      cultural and language-sensitive information booklet, was evaluated in a cluster
      randomized controlled trial (n = 310 immigrants). As a control condition there
      was a prevention event with materials from Deutsche Hauptstelle fur Suchtfragen
      (German Centre for Addiction Issues). Data were obtained before and after the
      event, as well as after 6 months. All materials were available both in German and
      in Russian, Italian, Spanish and Turkish. RESULTS: Directly after the event, as
      well as 6 months thereafter, the transcultural approach was rated significantly
      better than the general prevention event. 73.4 % of the participants read the
      cultural and migration-sensitive booklet, whereas only 21.2 % in the control
      condition (p = 0.0001). Furthermore, significantly more participants of the
      transcultural approach reported a reduced alcohol consumption (49.4 vs. 16.7 %; p
      = 0.004) after 6 months. CONCLUSION: The consideration of diversity with respect
      to cultural, migration-related, socio demographic und linguistic aspects improves
      the effectiveness of prevention measures.

PMID- 25963643
TI  - [Human plague and pneumonic plague : pathogenicity, epidemiology, clinical
      presentations and therapy].
AB  - Yersinia pestis is a highly pathogenic gram-negative bacterium and the causative
      agent of human plague. In the last 1500 years and during three dreaded pandemics,
      millions of people became victims of Justinian's plague, the Black Death, or
      modern plague. Today, Y. pestis is endemic in natural foci of Asian, African and
      American countries. Due to its broad dissemination in mammal species and fleas,
      eradication of the pathogen will not be possible in the near future. In fact,
      plague is currently classified as a "re-emerging disease". Infection may occur
      after the bite of an infected flea, but also after oral ingestion or inhalation
      of the pathogen. The clinical presentations comprise the bubonic and pneumonic
      form, septicemia, rarely pharyngitis, and meningitis. Most human cases can
      successfully be treated with antibiotics. However, the high transmission rate and
      lethality of pneumonic plague require international and mandatory case
      notification and quarantine of patients. Rapid diagnosis, therapy and barrier
      nursing are not only crucial for the individual patient but also for the
      prevention of further spread of the pathogen or of epidemics. Therefore, WHO
      emergency schedules demand the isolation of cases, identification and
      surveillance of contacts as well as control of zoonotic reservoir animals and
      vectors. These sanctions and effective antibiotic treatment usually allow a rapid
      containment of outbreaks. However, multiple antibiotic resistant strains of Y.
      pestis have been isolated from patients in the past. So far, no outbreaks with
      such strains have been reported. 

PMID- 25963644
TI  - [The "Black Death" : Crimean-Congo hemorrhagic fever].
AB  - The Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral disease that has
      been known for centuries. In the last years more frequent cases reflect the
      effects of climate change, globalization and the increasing encroachment of
      humans into previously unexploited areas. Humans acquire the infection by tick
      bites or through the slaughtering and processing of infected animals. The course
      of the disease can be severe and the average mortality reaches up to 30 %. It is
      transmissible from human to human and there is no causal treatment. Thus, CCHF
      meets the criteria for a highly contagious life-threatening disease. In the
      following current data on the virus, its vector, the distribution and
      transmission will be presented, as well as information on the diagnosis, the
      disease, the underlying pathophysiology and consequences in dealing with patients
      and deceased. 

PMID- 25963645
TI  - ITERATIVE SIFTING IN THE SELECTION OF RESEARCH EVIDENCE: IMPLICATIONS FOR REVIEWS
      AND OTHER DECISION PROBLEMS.
AB  - OBJECTIVES: A rapid scoping review was performed to support the development of a
      new clinical technology platform. An iterative sifting approach was adopted to
      address the challenges posed by the nature of the review question and the
      extremely large volume of search results to be sifted within the timescales of
      the review. METHODS: This study describes the iterative sifting approach applied
      in the scoping review and a preliminary validation of the methods applied.
      RESULTS: The searches performed for the rapid scoping review retrieved 27,198
      records. This was the full set of records subjected to the staged, iterative
      sifting approach and the subsequent validation process. The iterative sifting
      approach involved the screening for relevance of 17,354 (i.e., 63.8 percent) of
      the 27,198 records. A list of fifty-three potential biomarker names was generated
      as a result of this iterative sifting method, of which nineteen were selected by
      clinical specialists for further scrutiny. The preliminary validation involved
      the exhaustive sifting of the remaining 9,844 previously unsifted records. The
      validation process identified sixteen additional potential biomarker names not
      identified by the iterative sifting process. The clinical specialists
      subsequently concluded that none were of further clinical interest. CONCLUSIONS:
      This study describes an approach to the screening of search records that can be
      successfully applied in appropriate review and decision problems to allow the
      prioritization of the most relevant search records and achieve time savings.
      Following further refinement and standardization, this iterative sifting method
      may have potential for further applications in reviews and other decision
      problems.

PMID- 25963646
TI  - Solid phase extraction methodology for UPLC-MS based metabolic profiling of urine
      samples.
AB  - In general, when performing untargeted metabolic phenotyping
      (metabolomics/metabonomics) studies on biological samples for example urine or
      food, sample preparation should be kept to a minimum. However, there are
      circumstances when desalting, preconcentration, or the fractionation of samples
      into polar and nonpolar metabolites is of value for enabling the subsequent
      analysis. Because of its simplicity and ease of automation SPE is well suited to
      such applications prior to analysis by ultra-performance LC-TOF-MS. In the
      present study, the properties of a range of SPE phases have been investigated
      with respect to the range of metabolites that can be extracted from urine. The
      phases include alkyl modified (C8 and, C18-OH and C18) silica and polymeric
      materials. The results show that the C18 phase was well suited to fractionating
      urine into samples suitable for separate analysis of polar and nonpolar
      constituents via HILIC and RPLC, respectively, while the polymeric materials were
      best for concentrating and desalting samples.

PMID- 25963647
TI  - Genetic relatedness of commensal Escherichia coli from nursery pigs in intensive
      pig production in Denmark and molecular characterization of genetically different
      strains.
AB  - AIMS: To determine the genetic relatedness and the presence of virulence and
      antibiotic resistance genes in commensal Escherichia coli from nursery pigs in
      Danish intensive production. METHODS AND RESULTS: The genetic diversity of 1000
      E. coli strains randomly picked (N = 50 isolates) from cultured faecal samples (N
      = 4 pigs) from five intensive Danish pigs farms was analysed by repetitive
      extragenic palindromic-PCR (REP-PCR) and 42 unique REP-profiles were detected
      (similarity <92%). One profile was dominant (67.2% of strains) but farms differed
      significantly in the diversity of commensal E. coli: between eight and 21
      different profiles per farm were detected. One to three strains representing each
      REP-profile were characterized by multilocus typing scheme-typing, as well as for
      presence of antimicrobial and virulence genes and serogrouping through microarray
      analysis. The 42 REP-profiles were classified into 22 different sequence types
      (ST) with ST10 being the most common, encompassing 10 REP-profiles. Resistance
      and virulence genes were detected in most of the isolates. Genes encoding AmpC
      beta-lactamases and quinolone resistance were found in one and three isolates,
      respectively. Toxin-producing genes were observed in 20 isolates. CONCLUSIONS: A
      low genetic diversity was found in commensal gut E. coli from nursery pigs in
      Denmark. No correlation was observed between REP-profiles, ST-types and
      resistance/virulence patterns. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the
      first study analysing in depth the genetic variability of commensal E. coli from
      pigs in Danish intensive pig production. A tendency for higher diversity was
      observed with in nursery pigs that were treated with zinc oxide only, in absence
      of other antimicrobials. Strains with potential to disseminate virulence and
      antibiotic resistance genes to pathogenic subgroups of E. coli were found to be
      wide-spread.

PMID- 25963648
TI  - Determination of the triacylglycerol fraction in fish oil by comprehensive liquid
      chromatography techniques with the support of gas chromatography and mass
      spectrometry data.
AB  - Fish oil made from menhaden (Brevoortia tyrannus) can be used as a dietary
      supplement for the presence of high levels of the long-chained omega-3 fatty
      acids, viz. epentaenoic and docosahexanoic. In this work, for the first time, two
      different multidimensional approaches were developed and compared, in terms of
      peak capacity, for triacylglycerol characterization. In particular, silver ion
      chromatography with a silver-ion column and non-aqueous reverse-phase liquid
      chromatography with a C18 column were tested in both comprehensive (stop-flow)
      and off-line modes. The use of mass spectra attained by atmospheric pressure
      chemical ionization for both LC approaches, and the fatty acids methyl esters
      profile of menhaden oil obtained by gas chromatography analysis, greatly
      supported the elucidation of the triacylglycerol content in menhaden oil. The off
      line approach afforded a better separation and, thus, higher peak capacity to
      allow identifying and semiquantifying more than 250 triacylglycerols. Such a huge
      number has never been reported for a menhaden oil sample.The main disadvantage of
      such an approach over the stop-flow one was the longer analysis time, mainly
      attributable to solvent exchange between the two dimensions.

PMID- 25963649
TI  - LC-MS/MS-based quantification of cholesterol and related metabolites in dried
      blood for the screening of inborn errors of sterol metabolism.
AB  - Smith-Lemli-Opitz syndrome (SLOS) is an inherited metabolic disease in the
      cholesterol biosynthesis pathway which is characterised by accumulation of 7- and
      8-dehydrocholesterol and by reduced cholesterol concentrations in all tissues and
      body fluids. With this study, we developed a new, rapid, robust and high
      throughput tandem mass spectrometric method as routine application for the
      selective SLOS screening and therapy monitoring in serum and dried blood. After
      protein precipitation of 10 MUL serum or 4.7 mm dried blood spot, the sum of 7-
      and 8-dehydrocholesterol (DHC) was analysed by rapid chromatography combined with
      tandem mass spectrometry. Method comparison with GC-MS was performed for 46 serum
      samples. A comparison between serum and corresponding dried blood spots for DHC
      and cholesterol was performed with 40 samples from SLOS patients. Concentrations
      of DHC and cholesterol were analysed in 2 dried blood samples from newborns with
      SLOS and 100 unaffected newborns. Intra- and inter-assay variabilities ranged
      between 3.7 and 17.7% for serum and dried blood spots. Significant correlations
      between the new LC-MS/MS method and GC-MS were determined for DHC (r = 0.937, p <
      0.001) and for cholesterol (r = 0.946, p < 0.001). Significant coefficients of
      correlation between serum and dried blood spot samples above 0.8 were calculated
      for both analytes. A cut-off value of 5.95 for the ratio of DHC/cholesterol
      (multiplied by 1000) was found to distinguish newborns diagnosed with SLOS from
      normal newborns in a retrospective analysis after 5 years. The developed method
      enables a rapid quantification of the sum parameter 7- and 8-DHC in newborns and
      SLOS patients under therapy in serum as well as dried blood spot samples.

PMID- 25963650
TI  - Lipidomics.

PMID- 25963651
TI  - A new surfactant-introduction strategy for separating the pure single-phase of
      metal-organic frameworks.
AB  - By introducing different surfactants into a reaction system, two previous mixed
      phase Ni(II)-MOFs constructed from an undeveloped pyridyl-tetracarboxylate and
      Ni(II) salts were successfully isolated to obtain two pure products. Compound 1
      exhibits a 3D H-bonded network with (3,8)-connected
      {4.5(2)}2{4(2).5(6).6(14).7(2).8(4)} topology, while 2 features a 3D 2-fold
      interpenetrating framework with a self-penetrating (3,4,4)-connected
      {6(2).10(3).12}{6(3)}2{6(4).8.10}2 topological net.

PMID- 25963652
TI  - SLE myopathy: a clinicopathological study.
AB  - AIM: To study the histological changes in muscle biopsy in patients diagnosed
      with systemic lupus erythematosus (SLE) and presenting with muscle symptoms.
      MATERIALS AND METHODS: Patients with SLE presenting with muscle symptoms at
      presentation or during follow-up and treatment between January 2010 and May 2014
      and who underwent muscle biopsy were included in the study. Demographic, clinical
      features, serological markers, and Electromyoneurography findings were collected.
      Muscle biopsies were evaluated for inflammation, fiber type abnormalities,
      vasculitis and interstitial changes according to 2004 European Neuromuscular
      Centre criteria. RESULTS: Fifteen patients underwent muscle biopsy in the study
      period. Clinical presentations included mucocutaneous (9), musculoskeletal (14),
      hematological (3), renal (8), hepatic (1) and central nervous system (CNS) (4)
      manifestations, and neuropathy (4), serositis (2), Raynaud's phenomenon (1) and
      infectious complications (8). Histological findings were perivascular/perimysial
      inflammation (7/15), type 1 predominance (7/15) and type 2 atrophy (13/15).
      Clinical evidence of myositis was seen in 8.8% of patients in the SLE registry,
      whereas histological evidence of myositis was seen in 46.66% of biopsied patients
      with muscle symptoms. There was no significant difference in clinical,
      serological, laboratory and muscle histology features between groups of patients
      with or without myositis. Type 2 atrophy was the predominant finding in SLE
      patients irrespective of time of muscle biopsy, treatment received and presence
      or absence of myositis. CONCLUSIONS: Histological evidence of myositis was found
      in 46.66% of SLE patients and there were no significant differences in
      clinical/laboratory features in patients with or without myositis. Type 2 atrophy
      was seen in patients irrespective of time of the biopsy, treatment received and
      presence or absence of myositis. Type 2 atrophy was considered the major cause
      for muscle symptoms.

PMID- 25963653
TI  - Reference ranges and determinants of total hCG levels during pregnancy: the
      Generation R Study.
AB  - Human chorionic gonadotropin (hCG) is a pregnancy hormone secreted by the
      placental synctiotrophoblast cell layer that has been linked to fetal growth and
      various placental, uterine and fetal functions. In order to investigate the
      effects of hCG on clinical endpoints, knowledge on reference range (RR)
      methodology and determinants of gestational hCG levels is crucial. Moreover, a
      better understanding of gestational hCG physiology can improve current screening
      programs and future clinical management. Serum total hCG levels were determined
      in 8195 women participating in the Generation R Study. Gestational age specific
      RRs using 'ultrasound derived gestational age' (US RRs) were calculated and
      compared with 'last menstrual period derived gestational age' (LMP RRs) and a
      model-based RR. We also investigated which pregnancy characteristics were
      associated with hCG levels. Compared to the US RRs, the LMP RRs were lower, most
      notably for the median and lower limit levels. No considerable differences were
      found between RRs calculated in the general population or in uncomplicated
      pregnancies only. Maternal smoking, BMI, parity, ethnicity, fetal gender,
      placental weight and hyperemesis gravidarum symptoms were associated with total
      hCG. We provide gestational RRs for total hCG and show that total hCG values and
      RR cut-offs during pregnancy vary depending on pregnancy dating methodology. This
      is likely due to the influence of hCG on embryonic growth, suggesting that
      ultrasound based pregnancy dating might be less reliable in women with high/low
      hCG levels. Furthermore, we identify different pregnancy characteristics that
      influence total hCG levels considerably and should therefore be accounted for in
      clinical studies. 

PMID- 25963654
TI  - Spindle Checkpoint Factors Bub1 and Bub2 Promote DNA Double-Strand Break Repair
      by Nonhomologous End Joining.
AB  - The nonhomologous end-joining (NHEJ) pathway is essential for the preservation of
      genome integrity, as it efficiently repairs DNA double-strand breaks (DSBs).
      Previous biochemical and genetic investigations have indicated that, despite the
      importance of this pathway, the entire complement of genes regulating NHEJ
      remains unknown. To address this, we employed a plasmid-based NHEJ DNA repair
      screen in budding yeast (Saccharomyces cerevisiae) using 369 putative
      nonessential DNA repair-related components as queries. Among the newly identified
      genes associated with NHEJ deficiency upon disruption are two spindle assembly
      checkpoint kinases, Bub1 and Bub2. Both observation of resulting phenotypes and
      chromatin immunoprecipitation demonstrated that Bub1 and -2, either alone or in
      combination with cell cycle regulators, are recruited near the DSB, where
      phosphorylated Rad53 or H2A accumulates. Large-scale proteomic analysis of Bub
      kinases phosphorylated in response to DNA damage identified previously unknown
      kinase substrates on Tel1 S/T-Q sites. Moreover, Bub1 NHEJ function appears to be
      conserved in mammalian cells. 53BP1, which influences DSB repair by NHEJ,
      colocalizes with human BUB1 and is recruited to the break sites. Thus, while Bub
      is not a core component of NHEJ machinery, our data support its dual role in
      mitotic exit and promotion of NHEJ repair in yeast and mammals.

PMID- 25963655
TI  - Amino Acid-Dependent mTORC1 Regulation by the Lysosomal Membrane Protein SLC38A9.
AB  - The serine/threonine kinase mTORC1 regulates cellular homeostasis in response to
      many cues, such as nutrient status and energy level. Amino acids induce mTORC1
      activation on lysosomes via the small Rag GTPases and the Ragulator complex,
      thereby controlling protein translation and cell growth. Here, we identify the
      human 11-pass transmembrane protein SLC38A9 as a novel component of the Rag
      Ragulator complex. SLC38A9 localizes with Rag-Ragulator complex components on
      lysosomes and associates with Rag GTPases in an amino acid-sensitive and
      nucleotide binding state-dependent manner. Depletion of SLC38A9 inhibits mTORC1
      activity in the presence of amino acids and in response to amino acid
      replenishment following starvation. Conversely, SLC38A9 overexpression causes
      RHEB (Ras homolog enriched in brain) GTPase-dependent hyperactivation of mTORC1
      and partly sustains mTORC1 activity upon amino acid deprivation. Intriguingly,
      during amino acid starvation mTOR is retained at the lysosome upon SLC38A9
      depletion but fails to be activated. Together, the findings of our study reveal
      SLC38A9 as a Rag-Ragulator complex member transducing amino acid availability to
      mTORC1 activity.

PMID- 25963656
TI  - Rap1 Spatially Controls ArhGAP29 To Inhibit Rho Signaling during Endothelial
      Barrier Regulation.
AB  - The small GTPase Rap1 controls the actin cytoskeleton by regulating Rho GTPase
      signaling. We recently established that the Rap1 effectors Radil and Rasip1,
      together with the Rho GTPase activating protein ArhGAP29, mediate Rap1-induced
      inhibition of Rho signaling in the processes of epithelial cell spreading and
      endothelial barrier function. Here, we show that Rap1 induces the independent
      translocations of Rasip1 and a Radil-ArhGAP29 complex to the plasma membrane.
      This results in the formation of a multimeric protein complex required for Rap1
      induced inhibition of Rho signaling and increased endothelial barrier function.
      Together with the previously reported spatiotemporal control of the Rap guanine
      nucleotide exchange factor Epac1, these findings elucidate a signaling pathway
      for spatiotemporal control of Rho signaling that operates by successive protein
      translocations to and complex formation at the plasma membrane.

PMID- 25963657
TI  - Dysregulated Inflammatory Signaling upon Charcot-Marie-Tooth Type  1C Mutation of
      SIMPLE Protein.
AB  - Endosomal trafficking is a key mechanism to modulate signal propagation and cross
      talk. Ubiquitin adaptors, along with endosomal sorting complex required for
      transport (ESCRT) complexes, are also integrated to terminate ligand-receptor
      activation in late endosomes and multivesicular bodies (MVBs). Within these
      pathways, we recently demonstrated that the protein SIMPLE is a novel player in
      MVB regulation. SIMPLE is also clinically important and its mutation accounts for
      the Charcot-Marie-Tooth type 1C (CMT1C) disease. MVB defects of mutation and
      deletion of SIMPLE, however, are distinct. Here, we show that MVB defects found
      in mutation but not deletion of SIMPLE lead to impaired turnover and accumulation
      of ESCRT-0 protein Hrs punctain late endosomes. We further uncover increased
      colocalization of ubiquitin ligase TRAF6 and Hrs in late endosomes. Upon
      stimulation with interkeukin-1 or transforming growth factor , prolonged
      activation of p38 kinase/JNK is detected, while nuclear accumulation of NF-kappaB
      and phosphorylation of SMAD2 is reduced with CMT1C mutation. The aberrant
      kinetics we observed in inflammatory signaling may contribute to increased tumor
      susceptibility and changes in the levels of chemokines/cytokines that result from
      CMT1C mutation. We propose that altered endosomal trafficking due to
      malformations of MVBs and subsequent atypical signaling kinetic may account for a
      toxic gain of function in CMT1C pathogenesis.

PMID- 25963658
TI  - Regulated Intron Retention and Nuclear Pre-mRNA Decay Contribute to PABPN1
      Autoregulation.
AB  - The poly(A)-binding protein nuclear 1 is encoded by the PABPN1 gene, whose
      mutations result in oculopharyngeal muscular dystrophy, a late-onset disorder for
      which the molecular basis remains unknown. Despite recent studies investigating
      the functional roles of PABPN1, little is known about its regulation. Here, we
      show that PABPN1 negatively controls its own expression to maintain homeostatic
      levels in human cells. Transcription from the PABPN1 gene results in the
      accumulation of two major isoforms: an unspliced nuclear transcript that retains
      the 3'-terminal intron and a fully spliced cytoplasmic mRNA. Increased dosage of
      PABPN1 protein causes a significant decrease in the spliced/unspliced ratio,
      reducing the levels of endogenous PABPN1 protein. We also show that PABPN1
      autoregulation requires inefficient splicing of its 3'-terminal intron. Our data
      suggest that autoregulation occurs via the binding of PABPN1 to an adenosine (A)
      rich region in its 3' untranslated region, which promotes retention of the 3'
      terminal intron and clearance of intron-retained pre-mRNAs by the nuclear
      exosome. Our findings unveil a mechanism of regulated intron retention coupled to
      nuclear pre-mRNA decay that functions in the homeostatic control of PABPN1
      expression.

PMID- 25963659
TI  - Uncoupling Stress-Inducible Phosphorylation of Heat Shock Factor 1 from Its
      Activation.
AB  - In mammals the stress-inducible expression of genes encoding heat shock proteins
      is under the control of the heat shock transcription factor 1 (HSF1). Activation
      of HSF1 is a multistep process, involving trimerization, acquisition of DNA
      binding and transcriptional activities, which coincide with several
      posttranslational modifications. Stress-inducible phosphorylation of HSF1, or
      hyperphosphorylation, which occurs mainly within the regulatory domain (RD), has
      been proposed as a requirement for HSF-driven transcription and is widely used
      for assessing HSF1 activation. Nonetheless, the contribution of
      hyperphosphorylation to the activity of HSF1 remains unknown. In this study, we
      generated a phosphorylation-deficient HSF1 mutant (HSF1Delta~PRD), where the 15
      known phosphorylation sites within the RD were disrupted. Our results show that
      the phosphorylation status of the RD does not affect the subcellular localization
      and DNA-binding activity of HSF1. Surprisingly, under stress conditions,
      HSF1Delta~PRD is a potent transactivator of both endogenous targets and a
      reporter gene, and HSF1Delta~PRD has a reduced activation threshold. Our results
      provide the first direct evidence for uncoupling stress-inducible phosphorylation
      of HSF1 from its activation, and we propose that the phosphorylation signature
      alone is not an appropriate marker for HSF1 activity.

PMID- 25963660
TI  - Regulation of MicroRNA 183 by Cyclooxygenase 2 in Liver Is DEAD-Box Helicase p68
      (DDX5) Dependent: Role in Insulin Signaling.
AB  - Cyclooxygenase (COX) catalyzes the first step in prostanoid biosynthesis and
      exists as two isoforms. COX-1 is a constitutive enzyme involved in physiological
      processes, whereas COX-2 is induced by a variety of stimuli. MicroRNAs (miRNAs)
      are noncoding RNAs that function as key posttranscriptional regulators of gene
      expression. Although it is known that COX-2 expression is regulated by miRNAs,
      there are no data regarding COX-2 involvement in miRNA regulation. Considering
      our previous results showing that COX-2 expression in hepatocytes protects
      against insulin resistance, we evaluated the role of COX-2 in the regulation of a
      specific set of miRNAs implicated in insulin signaling in liver cells. Our
      results provide evidence of the molecular basis for a novel function of COX-2 in
      miRNA processing. COX-2 represses miRNA 23b (miR-23b), miR-146b, and miR-183
      expression in liver cells by increasing the level of DEAD-box helicase p68 (DDX5)
      through phosphatidylinositol 3-kinase (PI3K)/p300 signaling and by modulating the
      enzymatic function of the Drosha (RNase type III) complex through its physical
      association with DDX5. The decrease of miR-183 expression promotes protection
      against insulin resistance by increasing insulin receptor substrate 1 (IRS1)
      levels. These results indicate that the modulation of miRNA processing by COX-2
      is a key event in insulin signaling in liver and has potential clinical
      implications for the management of various hepatic dysfunctions.

PMID- 25963663
TI  - What are talent scouts actually identifying? Investigating the physical and
      technical skill match activity profiles of drafted and non-drafted U18 Australian
      footballers.
AB  - OBJECTIVES: To compare the physical and technical skill match activity profiles
      of drafted and non-drafted under 18 Australian football players. DESIGN: Cross
      sectional observational. METHODS: In-game physical and skill variables were
      assessed for under 18 Australian football players participating within the 2013
      and 2014 National under 18 Australian Football League Championships. Players
      originated from one State Academy (n=55). Ten games were analysed; resulting in
      183 observations. Players were sub-divided into two groups; drafted/non-drafted.
      Microtechnology and a commercial statistical provider allowed the quantification
      of total distance (m), relative distance (mmin(-1)), high speed running distance
      (>15kmh(-1)), high speed running expressed as a percentage of total distance (%
      total), total disposals, marks, contested possessions, uncontested possessions,
      inside 50s and rebound 50s (n=10). The effect size (d) of draft outcome on these
      criterion variables was calculated, with generalised estimating equations (GEE's)
      used to model which of these criterion variables was associated with draft
      outcome. RESULTS: Contested possessions and inside 50s reflected large effect
      size differences between groups (d=1.01, d=0.92, respectively). The GEE models
      revealed contested possessions as the strongest predictor of draft outcome, with
      inside 50s being the second. Comparatively, the remaining criterion variables
      were not predictive of draft outcome. CONCLUSIONS: Contested possessions and
      inside 50s are the most influential in-game variables associated with draft
      outcome for West Australian players competing within the National under 18
      Australian Football League Championships. Technically skilled players who win
      contested possessions and deliver the ball inside 50 may be advantageously
      positioned for draft success.

PMID- 25963662
TI  - Chromatin-Mediated Reversible Silencing of Sense-Antisense Gene Pairs in
      Embryonic Stem Cells Is Consolidated upon Differentiation.
AB  - Genome-wide gene expression studies have indicated that the eukaryotic genome
      contains many gene pairs showing overlapping sense and antisense transcription.
      Regulation of these coding and/or noncoding gene pairs involves intricate
      regulatory mechanisms. In the present study, we utilized an enhanced green
      fluorescent protein (EGFP)-tagged reporter plasmid cis linked to a doxycycline
      inducible antisense promoter, generating antisense transcription that fully
      overlaps EGFP, to study the mechanism and dynamics of gene silencing after
      induction of noncoding antisense transcription in undifferentiated and
      differentiating mouse embryonic stem cells (ESCs). We found that EGFP silencing
      is reversible in ESCs but is locked into a stable state upon ESC differentiation.
      Reversible silencing in ESCs is chromatin dependent and is associated with
      accumulation of trimethylated lysine 36 on histone H3 (H3K36me3) at the EGFP
      promoter region. In differentiating ESCs, antisense transcription-induced
      accumulation of H3K36me3 was associated with an increase in CpG methylation at
      the EGFP promoter. Repression of the sense promoter was affected by small
      molecule inhibitors which interfere with DNA methylation and histone
      demethylation pathways. Our results indicate a general mechanism for silencing of
      fully overlapping sense-antisense gene pairs involving antisense transcription
      induced accumulation of H3K36me3 at the sense promoter, resulting in reversible
      silencing of the sense partner, which is stabilized during ESC differentiation by
      CpG methylation.

PMID- 25963664
TI  - Size-controlled silver nanoparticles stabilized on thiol-functionalized MIL
      53(Al) frameworks.
AB  - A postsynthetic modification method was used to prepare thiol-functionalized
      metal-organic frameworks (MOFs) by the amidation of mercaptoacetic acid with the
      amine group, which is present in the frameworks of NH2-MIL-53(Al). By doing this,
      the thiol group has been successfully grafted on the MOF, which perfectly
      combined the highly developed pore structures of the MOF with the strong
      coordination ability of the thiol group. The resulting thiol-functionalized MIL
      53(Al) showed a significantly high adsorption capacity for heavy metal ions like
      Ag(+) (182.8 mg g(-1)). Even more importantly, these grafted thiol groups can be
      used as anchoring groups for stabilizing metal nanoparticles (NPs) with
      controllable sizes. Taking silver as an example, monodispersed Ag NPs
      encapsulated in the cages of MIL-53(Al) have been prepared by using a two-step
      procedure. In addition, the particle size of the Ag NPs was adjustable to some
      extent by controlling the initial loading amount. The average size of the
      smallest Ag NPs is 3.9 +/- 0.9 nm, which is hard to obtain for Ag NPs because of
      their strong tendency to aggregate. 

PMID- 25963661
TI  - Bhlhe40 Represses PGC-1alpha Activity on Metabolic Gene Promoters in Myogenic
      Cells.
AB  - PGC-1alpha is a transcriptional coactivator promoting oxidative metabolism in
      many tissues. Its expression in skeletal muscle (SKM) is induced by hypoxia and
      reactive oxidative species (ROS) generated during exercise, suggesting that PGC
      1alpha might mediate the cross talk between oxidative metabolism and cellular
      responses to hypoxia and ROS. Here we found that PGC-1alpha directly interacted
      with Bhlhe40, a basic helix-loop-helix (bHLH) transcriptional repressor induced
      by hypoxia, and protects SKM from ROS damage, and they cooccupied PGC-1alpha
      targeted gene promoters/enhancers, which in turn repressed PGC-1alpha
      transactivational activity. Bhlhe40 repressed PGC-1alpha activity through
      recruiting histone deacetylases (HDACs) and preventing the relief of PGC-1alpha
      intramolecular repression caused by its own intrinsic suppressor domain.
      Knockdown of Bhlhe40 mRNA increased levels of ROS, fatty acid oxidation,
      mitochondrial DNA, and expression of PGC-1alpha target genes. Similar effects
      were also observed when the Bhlhe40-mediated repression was rescued by a
      dominantly active form of the PGC-1alpha-interacting domain (PID) from Bhlhe40.
      We further found that Bhlhe40-mediated repression can be largely relieved by
      exercise, in which its recruitment to PGC-1alpha-targeted cis elements was
      significantly reduced. These observations suggest that Bhlhe40 is a novel
      regulator of PGC-1alpha activity repressing oxidative metabolism gene expression
      and mitochondrion biogenesis in sedentary SKM.

PMID- 25963665
TI  - Episodic future thinking: the role of working memory and inhibition on age
      related differences.
AB  - The ability to remember past events and imagine future events (episodic future
      thinking-EFT) has been shown to decline with aging. However, only few studies
      have analyzed the cognitive mechanisms involved in EFT in both young and older
      adults. The present study examined the role of working memory and inhibition on
      age-related differences between young and older adults in EFT, in response to
      short sentences reflecting common events, some of which were repeated in both
      conditions (past and future). Thirty-seven young and 36 older adults completed an
      adapted version of the autobiographical interview, in which sentences were
      presented. Results showed that processing resources explained a significant part
      of the variance in the amount of details; in particular, inhibition explained the
      amount of external details produced in the future condition. In addition, using
      sentences, the older group did not differ from the young adults in terms of the
      proportion of internal details recalled in the past condition, whereas they
      produced a lower proportion of internal details in the future condition. The
      effect of using structured material was reinforced by repeating some sentences in
      the past. Further, only older adults rated the remembered episodes as more
      emotionally salient and relevant than the imagined ones. Age-related differences
      between young and older adults in EFT appear to depend on the type of material
      used, on basic mechanisms of cognition, and are characterized by both
      quantitative and qualitative differences. 

PMID- 25963666
TI  - Identification of a novel potent, selective and cell permeable inhibitor of
      protein kinase CK2 from the NIH/NCI Diversity Set Library.
AB  - The anti-apoptotic protein kinase CK2 increasingly becomes an attractive target
      in cancer research with great therapeutic potential. Here, we have performed an
      in vitro screening of the Diversity Set III of the DTP program from the NCI/NIH,
      comprising 1600 compounds. We have identified 1,3-Dichloro-6-[(E)-((4
      methoxyphenyl)imino)methyl] dibenzo(b,d) furan-2,7-diol (referred to as D11) to
      be a potent and selective inhibitor of protein kinase CK2. The D11 compound was
      tested against 354 eukaryotic protein kinases. By setting the threshold for
      inhibition to <2% remaining kinase activity, only DYRK1B, IRAK1 and PIM3 were
      inhibited to an extent as the tetrameric CK2 holoenzyme and its catalytic
      subunits alpha and alpha'. The IC50 values for the CK2alpha and CK2alpha' were on
      average 1-2 nM in comparison to the DYRK1B, IRAK1 and PIM3 kinases, which ranged
      from 18 to 49 nM. Cell permeability and efficacy of D11 were tested with cells in
      culture. In MIA PaCa-2 cells (human pancreatic carcinoma cell line), the
      phosphorylation of the CK2 biomarker CDC37 at S13 was almost completely inhibited
      in the presence of D11. This was observed both under normoxia and hypoxia. In the
      case of the human non-small cell lung carcinoma cell line, H1299, increasing
      amounts of D11 led to an inhibition of S380/T382/383 phosphorylation in PTEN,
      another biomarker for CK2 activity.

PMID- 25963667
TI  - Contribution of mitochondrial function to exercise-induced attenuation of renal
      dysfunction in spontaneously hypertensive rats.
AB  - It is well known that exercise training exhibits renal protective effects in
      animal models of hypertension and chronic renal failure. However, the mechanisms
      regulating these effects of exercise training remain unclear. This study aimed to
      investigate the role of mitochondrial function in exercise-induced attenuation of
      renal injury in spontaneously hypertensive rats (SHR). The adult male SHR and age
      matched normotensive Wistar-Kyoto rats (WKY) were given moderate-intensity
      exercise for 12 weeks or treated with MitoQ10 for 8 weeks. In this work, exercise
      training in SHR reduced blood pressure, and effectively attenuated renal
      dysfunction, marked by reduced creatinine excretion, albuminuria, blood urea
      nitrogen, and glomerular sclerosis. Exercise training in SHR reduced MDA levels
      in plasma and kidneys and suppressed formation of 3-nitrotyrosine in kidneys.
      Exercise training suppressed mitochondrial ROS and [Formula: see text] formation,
      enhanced ATP formation, reduced mitochondrial swelling, and restored electron
      transport chain enzyme activity in kidneys of SHR. Furthermore, exercise training
      upregulated protein expression of uncoupling protein 2 and manganese superoxide
      dismutase in kidneys of SHR. In addition, treatment with mitochondria-targeted
      antioxidant MitoQ10 exhibited similar renal protective effects in SHR. In
      conclusion, chronic aerobic exercise training preserved mitochondrial function
      and abated oxidative stress in the kidneys of SHR, which may in part explain the
      protective effect of exercise on renal function and structure in hypertensive
      individuals.

PMID- 25963668
TI  - TNFalpha induces inflammatory stress response in microvascular endothelial cells
      via Akt- and P38 MAP kinase-mediated thrombospondin-1 expression.
AB  - Tumor necrosis factor-alpha (TNFalpha) and thrombospondin-1 (TSP-1) are well
      known mediators of inflammation. However, a causal relationship between TNFalpha
      stimuli and TSP-1 expression in endothelial cell stress, and the underlying
      mechanisms has not yet been investigated. In our study, human microvascular
      endothelial cells (hMEC) were treated with TNFalpha and analyzed for endothelial
      dysfunction, TSP-1 expression, and associated mechanisms. TNFalpha treatment
      induced a dose-dependent increase in TSP-1 expression in hMEC associated with
      increased endothelial permeability, apoptosis, and reduced proliferation. Whereas
      TNFalpha activated Akt, ERK, and P38 mitogen-activated protein kinase (P38 MAPK)
      simultaneously in hMEC, inhibitors of Akt and P38 MAPK, but not ERK blunted
      TNFalpha-induced TSP-1 expression. Silencing of NFkappaB gene had no significant
      effect on TNFalpha-induced TSP-1 expression. Our study demonstrates the novel
      role of TNFalpha in inducing inflammatory stress response in hMEC through Akt-
      and P38 MAPK-mediated expression of TSP-1, independent of NFkappaB signaling. 

PMID- 25963669
TI  - Mycorrhizal diversity, seed germination and long-term changes in population size
      across nine populations of the terrestrial orchid Neottia ovata.
AB  - In plant species that rely on mycorrhizal symbioses for germination and seedling
      establishment, seedling recruitment and temporal changes in abundance can be
      expected to depend on fungal community composition and local environmental
      conditions. However, disentangling the precise factors that determine recruitment
      success in species that critically rely on mycorrhizal fungi represents a major
      challenge. In this study, we used seed germination experiments, 454 amplicon
      pyrosequencing and assessment of soil conditions to investigate the factors
      driving changes in local abundance in 28 populations of the orchid Neottia ovata.
      Comparison of population sizes measured in 2003 and 2013 showed that nearly 60%
      of the studied populations had declined in size (average growth rate across all
      populations: -0.01). Investigation of the mycorrhizal fungi in both the roots and
      soil revealed a total of 68 species of putatively mycorrhizal fungi, 21 of which
      occurred exclusively in roots, 25 that occurred solely in soil and 22 that were
      observed in both the soil and roots. Seed germination was limited and
      significantly and positively related to soil moisture content and soil pH, but
      not to fungal community composition. Large populations or populations with high
      population growth rates showed significantly higher germination than small
      populations or populations declining in size, but no significant relationships
      were found between population size or growth and mycorrhizal diversity. Overall,
      these results indicate that temporal changes in abundance were related to the
      ability of seeds to germinate, but at the same time they provided limited
      evidence that variation in fungal communities played an important role in
      determining population dynamics. 

PMID- 25963670
TI  - The Organizational Account of Function is an Etiological Account of Function.
AB  - The debate on the notion of function has been historically dominated by
      dispositional and etiological accounts, but recently a third contender has gained
      prominence: the organizational account. This original theory of function is
      intended to offer an alternative account based on the notion of self-maintaining
      system. However, there is a set of cases where organizational accounts seem to
      generate counterintuitive results. These cases involve cross-generational traits,
      that is, traits that do not contribute in any relevant way to the self
      maintenance of the organism carrying them, but instead have very important
      effects on organisms that belong to the next generation. We argue that any
      plausible solution to the problem of cross-generational traits shows that the
      organizational account just is a version of the etiological theory and,
      furthermore, that it does not provide any substantive advantage over standard
      etiological theories of function. 

PMID- 25963671
TI  - In Silico Functional and Structural Characterization of H1N1 Influenza A Viruses
      Hemagglutinin, 2010-2013, Shiraz, Iran.
AB  - Hemagglutinin (HA) is a major virulence factor of influenza viruses and plays an
      important role in viral pathogenesis. Analysis of amino acid changes, epitopes'
      regions, glycosylation and phosphorylation sites have greatly contributed to the
      development of new generations of vaccine. The hemagglutinins of 10 selected
      isolates, 8 of 2010 and 2 of 2013 samples were sequenced and analyzed by several
      bioinformatic softwares and the results were compared with those of 3 vaccine
      isolates. The study detected several amino acid changes related to altered
      epitopes' sites, modification sites and physico-chemical properties. The results
      showed some conserved modification sites in HA structure. This study is the first
      analytical research on isolates obtained from Shiraz, Iran, and our results can
      be used to better understand the genetic diversity and antigenic variations in
      Iranian and Asian H1N1 pathogenic strains. 

PMID- 25963672
TI  - Short-term outcome of patients with possible transient ischemic attacks: a
      prospective study.
AB  - BACKGROUND: Patients with transient ischemic attack (TIA) have an increased risk
      of vascular events. There is scarce data regarding the prognosis of patients with
      transient neurological symptoms less typical of TIA, in whom a vascular origin
      cannot be excluded, also known as possible TIA. In this study we aimed to compare
      the short-term prognosis between TIA and Possible TIA patients. METHODS: Patients
      with transient neurological events consecutively referred to a TIA Clinic during
      five years were classified as TIA, Possible TIA or mimic. Patients were
      prospectively followed. We compared the outcome at 30 and 90 days after TIA or
      Possible TIA. The primary outcome was stroke and the secondary outcome was a
      combination of vascular events (stroke, TIA, myocardial infarction or vascular
      death). RESULTS: Two hundred and fifty eight TIA and 109 Possible TIA patients
      were included. Possible TIA patients had no stroke 30 and 90 days after the
      event. In contrast, 3.1 % and 4 % of TIA patients had stroke at the same time
      points. Combined vascular events occurred in 1.9 % of Possible TIA (myocardial
      infarction) and 9.8 % of TIA patients (stroke and TIA) after 30 days (OR = 0.18,
      95 % CI 0.04 to 0.76, P = 0.02); and in 1.9 % of Possible TIA patients
      (myocardial infarction) and 11.3 % of TIA patients (stroke and TIA) after 90 days
      (OR = 0.16, 95 % CI 0.04 to 0.67, P = 0.012). CONCLUSIONS: In this exploratory
      study, Possible TIA patients had less short-term vascular events than TIA
      patients.

PMID- 25963673
TI  - Chinese Herbal Medicine Xingnaojing Injection () for Hypoxic Ischemic
      Encephalopathy in Newborns: A Systematic Review and Meta-Analysis.
AB  - OBJECTIVES: To evaluate the efficacy and safety of Chinese herbal medicine
      Xingnaojing Injection () for newborns with hypoxic ischemic encephalopathy (HIE).
      METHODS: Literatures were identified by searching the PubMed, EMBASE, Cochrane
      Library, Cochrane Central, and four Chinese literature databases from the
      establishment of database to October in 2013. Relevant reference lists were also
      screened. Two reviewers independently evaluated the methodological quality of
      included studies. We also conducted the meta-analysis. RESULTS: Thirteen trials
      involving 1,169 patients were included. There was no trial reported death or
      disability at the end of follow-up period. Meta-analysis of 4 trials (n=371)
      showed that there was no significant difference in the reduction of mortality
      [risk ratios (RR)=0.48, 95% confidence intervals (CI, 0.21, 1.13), P=0.09]
      between the Xingnaojing and control groups. Meta-analysis of 5 trials (n=359)
      showed that there was significant difference in reducing the major
      neurodevelopmental disability [RR=0.36, 95% CI (0.19, 0.66), P=0.001]. Meta
      analysis of 6 trials (n=447) showed that there was significant difference in the
      author self-defined symptom improvement [RR=1.25, 95% CI (1.14, 1.37), P<0.01].
      No fatal side-effects were reported. CONCLUSION: Based on the limited evidence,
      the routine use of Xingnaojing Injection for treatment of HIE in newborns is not
      recommended. Further well-conducted trials are justified.

PMID- 25963674
TI  - Human papillomavirus genotypes distribution by cervical cytologic status among
      women attending the General Hospital of Loandjili, Pointe-Noire, Southwest Congo
      (Brazzaville).
AB  - HPV infection is associated with cervical cancer, one of the major public health
      problems in developing countries. In the Republic of Congo, despite of the high
      age-standardized incidence rate estimated at 25.2 per 100,000 women, molecular
      epidemiology data on HPV infections are very limited. We investigated HPV
      genotypes distribution in cervical smears among patients attending the General
      Hospital of Loandjili, Southwest Congo. A cross-sectional hospital-based study
      was conducted on 321 women. Liquid-based cytology samples were collected for
      cytological diagnosis and HPV detection. Nested-PCR was performed using MY09/MY11
      and GP5+/GP6+ primers with genotyping by direct sequencing. Type-specific PCR for
      HPV-6, -11, -16, -18, -31 and -33 was also used to assess multiple infections.
      Out of 321 women examined, 189 (58.8%) had normal cytology, 16 (5.0%) had ASCUS
      and 116 (36.1%) had cytological abnormalities. HPV-DNA was detected in 22
      (11.6%), 6 (37.5%), and 104 (89.6%) normal cytology, ASCUS and cytological
      abnormalities respectively. HPV16 was the most prevalent genotype regardless of
      cytological status followed by HPV70 in women without lesions and HPV33 among
      those with lesions. HR-HPV prevalence varied significantly according to the
      cervical cytology (P = 0.000). Among women without lesions, two peaks of HPV
      infections were observed in age group less than 30 years (60.0%) and in age group
      50-59 years (7.1%). Age, age of first sex, multiple sexual partners and
      pregnancies were the risk factors for HPV infection in women without lesions. Our
      findings could be used as evidence data base for future epidemiological
      monitoring in this region.

PMID- 25963675
TI  - Comparison of 4 supraglotttic devices used by paramedics during simulated CPR : a
      randomized controlled crossover trial.
AB  - BACKGROUND: Ensuring an open airway during cardiopulmonary resuscitation is
      fundamental. The aim of this study was to determine the success rate of blind
      intubation during simulated cardiopulmonary resuscitation by untrained personnel.
      METHODS: Four devices were compared in a simulated resuscitation scenario: ILMA
      (Intavent Direct Ltd, Buckinghamshire, United Kingdom), Cobra PLA (Engineered
      Medical Systems Inc, Indianapolis, IN), Supraglottic Airway Laryngopharyngeal
      Tube (SALT) (ECOLAB, St. Paul, MN), and Air-Q (Mercury Medical, Clearwater, FL).
      A group of 210 paramedics intubated a manikin with continuous chest compressions.
      RESULTS: The mean times to intubation were 40.46 +/- 4.64, 33.96 +/- 6.23, 17.2
      +/- 4.63, and 49.23 +/- 13.19 seconds (SALT vs ILMA, Cobra PLA, and Air-Q; P <
      .05). The success ratios of blind intubation for the devices were 86.7%, 85.7%,
      100%, and 71.4% (SALT vs ILMA, Cobra PLA, and Air-Q; P < .05). CONCLUSION: The
      study showed that the most efficient device with the shortest blind intubation
      time was the SALT device.

PMID- 25963676
TI  - Comparison of clinical characteristics of intentional vs accidental drowning
      patients.
AB  - PURPOSES: Drowning may happen by accident or as a method of committing suicide.
      The aim of this study was to determine some characteristics of drowning patients
      who committed intentionally. METHODS: A retrospective review was performed on 462
      patients who visited the emergency department complaining of drowning between
      January 1998 and October 2011. Of these patients, we only included the patients
      for whom the cause could be identified. Age, sex, cause, time of drowning,
      season, mechanism, cardiopulmonary resuscitation performance, body temperature,
      alcohol ingestion, history of previous suicide attempts, outcome, and other
      characteristics were collected. RESULTS: A total of 380 patients were included.
      Among them, 282 (74.2%) had drowned themselves intentionally, and they were older
      than those who had drowned accidentally (median age, 35.0 years [25.0-49.0 years]
      vs 26.5 years [19.0-35.5 years], P < .001) and showed lower body temperature
      (below 34 degrees C, 32.1% vs 12.2%, P = .027). Ninety-four cases (33.3%) jumped
      off the river from a bridge, and 185 (65.6%) walked into the river from the
      riverside. In the intentional group, 59 (20.9%) had depressive disorder in their
      history. The rate of death showed no clinical difference (19.5% vs 16.3%, P =
      .487), but more males died in the accidental group (61.8% vs 93.8%, P = .015).
      CONCLUSIONS: Intentional drowning happened more in older subjects and presented
      lower initial body temperature. Walking from the riverside happened more often
      than jumping off a bridge. More males died of drowning regardless of
      intentionality.

PMID- 25963677
TI  - Lung ultrasound for chest tube insertion.

PMID- 25963678
TI  - Authors' response to "peripartum cardiomyopathy in the ED".

PMID- 25963679
TI  - Randomized crossover trial of laryngeal tube exchange by paramedics during
      simulated resuscitation.

PMID- 25963680
TI  - The impact of goal-directed transvaginal ultrasonography on clinical decision
      making for emergency physicians.
AB  - The aim of study was to determine the impact of "goal-directed transvaginal
      ultrasonography" (TVUSG) on real-time clinical decision making of attending
      emergency physicians evaluating their level of certainty for preliminary
      diagnosis, admission, surgery, treatment, additional laboratory, and discharge in
      patients presenting with acute pelvic pain to the emergency department (ED). This
      prospective cross-sectional clinical study was conducted on sexually active
      female patients older than 18 years who presented with acute pelvic pain in the
      ED. The level of certainty of clinical decision making as mentioned above was
      measured by a visual analogue scale from 0 to 100 mm with 100 mm being most
      certain before and after TVUSG. Statistical analysis was performed on 88
      patients. The mean age was 31.7 +/-8.3 years with a median of 30 years. Among
      clinical decisions, there was a significant difference between pre-TVUSG and post
      TVUSG certainty of the decision to perform preliminary diagnoses derived from
      patient's history and physical examination but not in the other outcomes
      (treatment, admission, surgery, and discharge). (P = .05). Of the patients
      included in the study, 11 (12.5%) were admitted to hospital, and 2 (2.3%) of them
      were operated on. The remaining 75 (85.2%) patients were discharged from the ED;
      of the patients that had been discharged, 18 (20.5%) patients later consulted
      another physician, and no further pathology could be discovered. In conclusion,
      US performed by attending emergency physicians may affect the certainty of their
      decisions in patients presenting with acute pelvic pain. This effect
      statistically significantly on the decision to determine preliminary diagnosis. 

PMID- 25963681
TI  - Prehospital endotracheal intubation vs extraglottic airway device in blunt
      trauma.
AB  - OBJECTIVE: The objective of the study is to compare outcomes in blunt trauma
      patients managed with prehospital insertion of an extraglottic airway device
      (EGD) vs endotracheal intubation (ETI). The null hypothesis was that there would
      be no difference in mortality for the 2 groups. METHODS: This is a retrospective
      study of blunt trauma patients with Glasgow Coma Scale score less than or equal
      to 8 transported by ground emergency medical services directly from the scene of
      injury to a single urban level 1 trauma center. Patients managed with only
      noninvasive airway techniques were excluded, leaving patients undergoing either
      EGD placement or ETI. Outcomes included in-emergency department (ED) traumatic
      arrest and hospital mortality. Multivariable logistic regression was used to
      control for the potential confounding effects of demographic and clinical
      variables. For all analyses, P < .05 was used to establish statistical
      significance. RESULTS: In bivariate analysis, patients managed with EGD were more
      likely than those managed with ETI to have an in-ED traumatic arrest (36.5% vs
      17.1%; P = .005), but eventual hospital mortality did not significantly differ
      between the 2 groups (75.7% vs 67.1%; P = .228). After controlling for
      demographic and clinical characteristics, patients managed with EGD were no more
      likely than patients managed with ETI to experience traumatic arrest in the ED
      (adjusted odds ratio, 1.67; 95% confidence interval, 0.72-3.89), and there was
      also no difference in overall hospital mortality (adjusted odds ratio, 0.912; 95%
      confidence interval, 0.36-2.30). CONCLUSION: In this preliminary, retrospective
      analysis, we found no difference in overall survival among trauma patients
      managed with prehospital EGD and those managed with prehospital ETI.

PMID- 25963682
TI  - Heart block or cardiac arrest is not a contraindication for intravenous treatment
      with diltiazem in the setting of coronary spasm.

PMID- 25963683
TI  - Anti-Viral Agents in Neurodegenerative Disorders: New Paradigm for Targeting
      Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease affecting geriatric
      populations for which several causes have been proposed. These include a
      relationship with known pathogens although the exact nature of such a
      relationship remains uncertain. Herpes simplex virus-1 has been proposed as
      potential cause of AD because of its ability to form beta amyloid(Abeta) and
      neurofibrillary tangles due to tau hyperphosphorylation and action of beta &
      gamma secretase on amyloid precursor protein(APP) together with genetic
      association with apolipoprotein-E4(ApoE-E4), which points out to latent Herpes
      Simplex virus-1 as an agent causing AD. There are numerous studies that linked
      HSV-1 with AD like anti-HSV-1 IgM antibodies, nectin-2, heme oxygenase-1,
      phosphorylated eukaryotic initiation factor-2A, caspase-8 and nucleus-specific
      alteration of raphe neurons. Various possible mechanisms by which HSV-1 might
      lead to development of AD such as ApoE, beta-amyloid, tau phosphorylation,
      inflammation and oxidative stress are also discussed. Thus, this review discusses
      patent information and a strong relationship between latent HSV-1 and AD and also
      proposes antiviral therapy for AD. 

PMID- 25963684
TI  - [Legislation of cancer registries in Japan- an outline of the national cancer
      registry].
AB  - The national cancer registry in Japan will commence operations in January 2016
      under the Cancer Registry Promotion Act, which was established in December 2013.
      Although data on cancer incidence and survival rates in Japan have been available
      for limited regions for a long time, accurate nationwide data obtained from the
      national cancer registry database will contribute to the planning and evaluation
      of cancer control in Japan. It is expected that this database will be utilized in
      evaluating the quality of medical care for cancer patients, in assessing the
      accuracy of cancer screening, and in follow-up surveys in nationwide cohort
      studies. Furthermore, under the Cancer Registry Promotion Act, hospitals will be
      permitted to obtain vital patient information from data registered in the
      national cancer registry database, which will promote the publication of survival
      rates for cancer patients and accelerate research at hospitals. The founding of
      the Japanese national cancer registry is a landmark development in the promotion
      of cancer control and cancer research in Japan and it is essential that the
      Japanese population benefits from the information obtained from this database. 

PMID- 25963685
TI  - [Advance of salvage chemotherapy for colorectal cancer].
AB  - Oxaliplatin, irinotecan, and 5-fluorouracil in combination with or without
      targeted therapies are now well-documented treatment options for first- and
      second-line treatments of metastatic colorectal cancer. Furthermore, many
      guidelines regard these treatment options as the standard of care of the disease.
      However, there is much less data on the beneficial effect of salvage systemic
      therapy. Therefore, salvage treatment for patients with metastatic colorectal
      cancer after the use of approved drugs or their combinations is reviewed here.
      Conventional chemotherapeutic agents such as capecitabine, mitomycin C, and
      gemcitabine have limited or no activity when used as salvage treatment.
      Antiangiogenic drugs may postpone further progression and prolong survival.
      Regorafenib and TAS-102 have been established as salvage therapy agents. Further
      prospective phase III trials comparing an investigational drug alone or in
      combination with best supportive care as third- or later lines of treatment in
      metastatic colorectal cancer are highly warranted. Moreover, it is crucial to
      identify predictive biomarkers and improve our understanding of molecular
      mechanisms. 

PMID- 25963686
TI  - [Advances in secondary chemotherapy for gastric cancer].
AB  - Although both the response rate and survival time of patients with metastatic or
      recurrent gastric cancer have improved through the development of new anti-cancer
      agents, it is still difficult to achieve a complete response(CR)of a tumor.
      Compared to the best supportive care alone, second-line chemotherapy can prolong
      survival after the failure of first-line therapy in patients who otherwise are in
      good health. In the WJOG4407 trial, which compared irinotecan and paclitaxel as
      secondary chemotherapies, there was no difference in response rate or survival
      time. A large proportion of these patients could undergo third-line chemotherapy,
      and paclitaxel is currently used as a control in many secondary chemotherapy
      trials. The molecularly targeted agents ramucirumab and apatinib have been shown
      to have high efficacy in phase III trials. Ramucirumab will be approved for
      medical insurance reimbursement next year in Japan, and its combination with
      paclitaxel is considered the standard treatment for this malignancy. 

PMID- 25963687
TI  - [Second-line chemotherapy for advanced pancreatic cancer].
AB  - Many investigators have attempted to reach a consensus, though with limited
      evidence available, on second-line chemotherapy for advanced pancreatic cancer.
      Specifically, treatment consists of gemcitabine-based regimens and 5-FU-based
      regimens. The regimen that is not used for first-line chemotherapy will be used
      as second-line chemotherapy. In Japan, S-1 is frequently used in 5-FU-based
      regimens. When the FOLFIRINOX regimen is used as first-line chemotherapy,
      gemcitabine is recommended as second-line chemotherapy. On the other hand, when
      nab-PTX/gemcitabine is used as first-line chemotherapy, S-1 is recommended as
      second-line chemotherapy. 

PMID- 25963688
TI  - [Progress in second-line therapies for metastatic breast cancer].
AB  - It may be difficult to achieve complete cure for most metastatic breast cancer
      patients;thus, prolongation of overall survival and maintenance of the quality of
      life are often the main focus of treatment. In the treatment of metastatic breast
      cancer patients, it is important to choose the most appropriate therapeutic
      strategy based on substantial evidence that considers the biology of the tumor,
      including estrogen receptor(ER), progesterone receptor(PgR), and human epidermal
      growth factor receptor 2(HER2)status;the site and extent of the metastatic
      focus;the time to recurrence;prior treatment regimens;age; menopausal
      status;performance status;and the preference of the patient. A clinical subtype
      classification that is based on the tumor biology is typically utilized for
      devising a treatment strategy specific to each subtype. Expressly, first-line
      treatment options may include hormone therapy for hormone-positive breast
      cancers, antiHER2 therapy for HER2-positive breast cancers, and chemotherapy for
      hormone-negative and HER2-negative(triple negative)breast cancers. In recent
      years, with the development of regimens that are effective for every subtype, the
      treatments for breast cancer have undergone significant changes. In this section,
      we introduce the progress in the treatment for metastatic breast cancer, focusing
      specifically on second-line therapies according to each subtype. 

PMID- 25963689
TI  - [Tend to second-line therapy in lung cancer].
AB  - Second-line chemotherapy has been established for non-small-cell lung
      cancer(NSCLC)and sensitive relapsed small cell lung cancer(SCLC).Molecular
      targeted drugs, such as EGFR- and ALK-inhibitors, have improved survival outcome
      remarkably in patients with NSCLC harboring EGFR mutations or EML4-ALK fusion
      proteins.In addition, targeted drugs that may overcome T790M-mediated EGFR-TKI
      resistance have been developed, and the development of future therapeutic
      strategies is anticipated.On the other hand, molecular targeted drugs against
      SCLC have not yet been developed. 

PMID- 25963690
TI  - [Introduction of oxaliplatin for treating unresectable advanced or recurrent
      gastric cancer in clinical practice].
AB  - On the basis of public knowledge-based application, oxaliplatin has recently been
      approved for treating unresectable advanced or recurrent gastric cancer. With the
      introduction of oxaliplatin in clinical practice, SOX or CapeOX will be widely
      used for treating advanced gastric cancer. The safety data of SOX(oxaliplatin
      100mg/m2)in Japanese patients with advanced gastric cancer has been reported in a
      domestic phase III clinical trial. Nevertheless, when using SOX(oxaliplatin 130
      mg/m2), it is important to refer to the dose modification criteria given in the
      SOFT trial. This manuscript summarizes some clinical trials as references and the
      points to consider while using oxaliplatin for treating gastric cancer in
      clinical practice. 

PMID- 25963691
TI  - [Results of a drug use investigation of nanoparticle albumin-bound Paclitaxel for
      breast cancer].
AB  - A drug use investigation of nanoparticle albumin-bound paclitaxel was conducted
      based on conditions for approval. A total of 963 patients were enrolled in this
      study from September 24, 2010 to February 14, 2011. Twenty-nine patients were
      excluded, and a total of 934 patients were evaluated for determining the safety
      of nanoparticle albumin-bound paclitaxel. Adverse drug reactions were observed in
      92.8%of the patients, and major adverse drug reactions included myelosuppression
      and peripheral sensory neuropathy, both of which are characteristic adverse
      reactions of paclitaxel treatment. Both adverse drug reactions were observed at a
      high frequency after the second course of treatment, resulting in these reactions
      being primary causes for discontinuation. Increase in the rates of continuous
      drug administration may be accomplished by carrying out laboratory tests and
      noting the medical history in order to prevent myelosuppression from becoming
      serious and to perform earlier countermeasures for peripheral sensory neuropathy,
      leading to improved therapeutic effects. 

PMID- 25963692
TI  - [A questionnaire survey on QOL and toxicity in colorectal cancer survivors who
      received adjuvant chemotherapy].
AB  - The relative risk of cancer recurrence with postoperative adjuvant FOLFOX/CapeOX
      therapy(Ox)for stage III colorectal cancer is reduced by approximately 20%when
      compared to that with fluorouracil plus Leucovorin. We performed a questionnaire
      survey to evaluate the quality of life(QOL)and extent of side effects in patients
      who received adjuvant chemotherapy. In order to evaluate the risks and benefits
      of oxaliplatin administration, we also examined the differences in awareness of
      oxaliplatin side effects between patients and medical staff. Responses were
      obtained from 147 patients, 54 doctors, and 84 nurses. Analysis of the patient
      responses showed higher current QOL scores regardless of the chemotherapy
      regimen, although patients in the Ox group had a high rate of residual sensory
      peripheral neuropathy. In the Ox group, 81% of patients responded that the side
      effects were moderate. In contrast, 40% of medical staff identified the side
      effects of oxaliplatin as severe, which differed from that reported by the
      patients. Considering that Ox adjuvant chemotherapy may reduce the risk of
      recurrence by approximately 20%, the risk/benefit balance is acceptable. 

PMID- 25963693
TI  - [The effect of routine professional oral care on oral mucositis in hematologic
      chemotherapy patients].
AB  - BACKGROUND: According to the literature, 40%of all oral complications associated
      with chemotherapy are due to oral mucositis. Moreover, such complications
      increase the difficulties associated with oral intake, leading to deterioration
      of the patient's nutritional condition and increasing the risk of systemic
      infection. Therefore, oral mucositis prevention and proper treatment are very
      important. PATIENTS AND METHODS: The conditions of intra-oral cavities and
      effects of oral care in patients with hematological malignancies were
      retrospectively evaluated by dental hygienists from April 2008 to March 2011.
      RESULTS: Eleven of 28 patients(39.3%)who received routine professional oral care
      developed oral mucositis. In many such patients, intra-oral cavity deterioration,
      evidenced by a coated tongue and Candida infection, was observed. Although 25 of
      28 patients with hematologic malignancies received specific oral mucositis care
      after chemotherapy initiation, those receiving continuous oral care subsequently
      made a full recovery. CONCLUSIONS: These results suggest that early and
      continuous professional oral health care may play an important role in the
      effective chemotherapy of patients with hematologic malignancies.

PMID- 25963694
TI  - [Satisfaction with immunotherapy in patients with advanced cancer].
AB  - Patient satisfaction with cancer immunotherapy, which is not covered by health
      insurance in Japan, was evaluated among 65 patients with advanced cancer who had
      received immunotherapy in our hospital for 2 years. Satisfaction measures were
      based on patients' expectations for medical care, cost, and staff services, and
      involved a questionnaire consisting of 25 items. Results of the questionnaire
      analysis showed that most patients, who expected much of antigen-specific
      vaccination such as dendritic cells (DC) pulsed tumor-associated antigens, were
      dissatisfied with the high cost of private immunotherapy(i. e., not covered by
      medical insurance), and were unable to perceive the effectiveness of the
      treatment because there was no quantitative analysis of killer T cells induced by
      immunotherapy. Therefore, it is critically important for us to confirm the safety
      and efficiency of cancer immunotherapy, before introducing medical insurance for
      cancer patients in Japan. In addition, the quantitative measurement of killer T
      cells induced by DC peptide vaccines should be considered, to meet patients'
      expectations.

PMID- 25963696
TI  - [A female chronic myeloid leukemia patient who gave birth after stopping imatinib
      intentionally but who maintained a major molecular response with interferon].
AB  - Imatinib was administrated to a 38-year-old woman with chronic myeloid
      leukemia(CML). A major molecular response (MMR)(<=5 copies/0.5 MUgRNA in Amp-CML
      detected using the transcription mediated amplification/hybridization protection
      assay(TMA/HPA)method)was achieved in 18 months. She maintained MMR for 10 months,
      and wished to become pregnant. Imatinib was stopped intentionally because she
      wished to plan a pregnancy, but we prescribed interferon alpha (IFN-a)due to the
      likelihood of the CML recurring after pregnancy. The nausea caused by IFN-a was
      improved by administrating it during the night, and she gave birth to a healthy
      baby by a normal delivery, whilst maintaining MMR. In this case, IFN-a treatment
      gave good clinical results, the patient's prognosis was improved, and she could
      maintain a good quality of life. We consider this to be an informative example of
      IFN-a therapy for CML during pregnancy.

PMID- 25963695
TI  - [Safety of pemetrexed according to the duration of vitamin B12 and folic acid
      supplementation prior to the first dose of pemetrexed].
AB  - OBJECTIVE: Administration of vitamin B12 and folic acid for 7 days prior to the
      administration of the first dose of pemetrexed is recommended. However, vitamin
      supplementation rarely is initiated less than 7 days prior to the first dose of
      pemetrexed. Therefore, we analyzed the safety of pemetrexed with vitamin
      supplementation for less than 7 days prior to the first dose of pemetrexed.
      METHODS: Patients were classified into 2 groups according to the duration of
      vitamin supplementation prior to the first dose of pemetrexed: group A received
      vitamin supplementation for 7 days or more, and group B received vitamin
      supplementation for less than 7 days. We analyzed adverse effects, such as
      myelosuppression, rash, and diarrhea, after 1 cycle of pemetrexed therapy.
      RESULTS: A total of 70 patients were administered pemetrexed; 40 patients were
      men and 30 were women with a median age of 64.5 years(range, 43-86 years). A
      total of 57 patients were classified into group A and 13 into group B; 33
      patients were administered pemetrexed as a first-line treatment. Neutropenia of
      Grade 3 or more was observed in 4/49(8.2%)patients in group A and
      2/13(15.4%)patients in group B(p=0.60). There were no significant differences in
      the rates of occurrence of neutropenia, rash, and diarrhea. CONCLUSION: This
      retrospective study indicated that patients could be safely treated with
      pemetrexed if vitamin supplementation is initiated for less than 7 days prior to
      the first administration of pemetrexed. However, further studies are needed
      because of a lack of statistical power and adjustment for confounding factors.

PMID- 25963697
TI  - [Complete response in a case of advanced oropharyngeal cancer (T4aN2bM0) treated
      with concomitant cetuximab and radiotherapy].
AB  - We report favorable results achieved using a combination of cetuximab and
      radiotherapy to treat an elderly patient with advanced oropharyngeal cancer
      complicated by cardiovascular disease and renal dysfunction.The case was a 78
      year-old man who was referred to our hospital with the chief complaint of
      pharyngeal pain and swelling of the right side of the neck. The patient was
      diagnosed with oropharyngeal cancer (T4aN2bM0) based on a cytological diagnosis
      of Class V squamous cell carcinoma and CT findings.Because the patient had a
      history of hypertension, chronic renal failure, diabetes mellitus, cerebral
      infarction, angina pectoris, and prostate cancer, we determined that surgical
      excision and chemoradiotherapy using platinum-based drugs would be difficult.We
      therefore treated the patient with a combination of cetuximab and radiotherapy.
      Grade 3 mucous membrane disorder and Grade 2 dermatitis were observed during the
      course of treatment, but the treatment was completed without any other adverse
      events.A contrasted CT image taken after the completion of treatment showed that
      the primary tumor and cervical lymph node metastases had disappeared and the
      patient thus achieved a complete response.As of 6 months after treatment, there
      has been no recurrence or metastasis.As shown in this case, combination therapy
      with cetuximab and radiotherapy can be curative even in elderly patients with
      advanced oropharyngeal cancer and numerous complicating conditions.

PMID- 25963698
TI  - [A case of HER2-positive breast cancer for which preoperative chemotherapy with
      pertuzumab resulted in a pathological complete response].
AB  - A right breast tumor was identified during screening in a 56-year-old woman, and
      she was then diagnosed with Stage II B breast cancer (T2N1M0) of Luminal -HER2
      type. She was treated with preoperative chemotherapy with pertuzumab,
      trastuzumab, and docetaxel followed by epirubicin, cyclophosphamide, and
      fluorouracil. She was judged to have achieved a clinical complete response after
      4 courses of pertuzumab, trastuzumab, and docetaxel, and she then underwent
      partial resection of the right breast and sentinel lymph node dissection.
      Pathological examination revealed that a pathological complete response was
      achieved. Combination therapy with pertuzumab, trastuzumab, and docetaxel seems
      to be a useful preoperative chemotherapy regimen for HER2-positive breast cancer.

PMID- 25963699
TI  - [Long-term survival of a breast cancer patient with carcinomatous pleuritis and
      carcinomatous cardiac tamponade successfully treated by multimodality therapy].
AB  - A 69-year old woman was admitted to our hospital because of dyspnea and pain in
      her left breast. Computed tomography revealed a massive quantity of left pleural
      effusion, a tumor in the left breast(5 cm in diameter), left cervical and
      supraclavicular lymph node metastasis, and a large left axillary metastatic mass.
      Based on a core needle biopsy, her breast tumor was diagnosed pathologically as
      scirrhous carcinoma, which was positive for estrogen receptor/progesterone
      receptor and negative for HER2 using the FISH assay, and left pleural metastasis
      was diagnosed cytologically. The carcinomatous pleural effusion was successfully
      controlled using pleural instillations of pirarubicin HCl and OK-432 after
      pleural drainage. A near clinical complete response was achieved by EC systemic
      chemotherapy(6 months)followed by endocrine therapy(letrozole), but 3 months
      later she was diagnosed cytologically with carcinomatous cardiac tamponade. After
      operative pericardial drainage, intrapericardial instillations of cisplatin and
      OK-432 successfully prevented re-accumulation of pericardial effusion. Systemic
      chemotherapy(weekly paclitaxel)for 11 months and endocrine
      therapy(letrozole)resulted in a clinical complete response. One year and 10
      months after pericardial drainage, she underwent surgery(mastectomy and axillary
      lymph node dissection level II)because of two small tumors in the left breast
      which were found to be malignant using PET-CT. One tumor(diameter 1.6 cm)was
      found pathologically to consist of degenerated cancer cells, and another
      tumor(diameter 2 cm)was diagnosed as recurrent cancer. There was no lymph node
      metastasis in the axilla except for a single mass(1.4*0.7*0.3 cm), which was
      composed of extremely degenerative and necrotic non-lymphoid cancerous tissue.
      Since having the surgery, she has not experienced recurrence on hormone therapy
      with fulvestrant, and to date she is still alive, 3 years and 5 months since the
      left pleural metastasis episode. 

PMID- 25963700
TI  - [Nab-Paclitaxel with platinum chemotherapy as sixth-line therapy for a non-small
      cell lung cancer patient].
AB  - A 48-year-old woman was admitted to our hospital for sixth-line chemotherapy. A
      chest X-ray film and computed tomographic (CT) scan revealed a right-sided
      massive tumor with multiple lung tumors. Repeated treatment with carboplatin (AUC
      6) on day 1 and nab-paclitaxel (100mg/m2) on days 1, 8, and 15, every 28 days
      were effective in this patient. Chemotherapy with nab-paclitaxel may be effective
      for patients with multi-recurrent adenocarcinoma.

PMID- 25963701
TI  - [Three cases of esophageal carcinoma achieved a pathological complete response
      after neoadjuvant chemotherapy with cisplatin and 5-fluorouracil].
AB  - We report three cases of esophageal carcinoma all of which achieved a
      pathological complete response after neoadjuvant chemotherapy (NAC) with
      cisplatin and 5-fluorouracil (CF). All three patients were men with clinical
      stage II squamous cell carcinoma of the middle thoracic esophagus. We
      administered 2 courses of CF treatment as NAC and then performed radical
      esophagectomy. Pathologic examination revealed no viable tumor cells in the
      resected esophagus. The patients are currently alive with no evidence of disease.

PMID- 25963702
TI  - [Long-term survival and effective treatment of synchronous liver metastases in a
      case of primary gastric choriocarcinoma by using hepatic arterial infusion
      chemotherapy, irinotecan, and cisplatin].
AB  - A 62-year-old man was admitted to our hospital because of appetite loss. Computed
      tomography(CT)revealed thickness of the gastric wall, multiple liver tumors, and
      lung nodes. Upper gastrointestinal endoscopy revealed an easy bleeding type 2
      tumor at the gastric antrum. We performed distal gastrectomy to control bleeding
      from the gastric tumor. Histological findings from the gastric lesion indicated
      primary gastric choriocarcinoma(PCG). Combination chemotherapy using hepatic
      arterial infusion chemotherapy for synchronous liver metastases and S-1 was
      administered for 5 months after the operation. CT revealed that the liver
      metastases decreased remarkably. On the other hand, lung metastases increased.
      Irinotecan and cisplatin were administered. Liver metastases did not increase, as
      observed using imaging studies. The patient died 17 months after the operation
      for cachexia. PCG is a highly aggressive tumor that is often associated with
      liver metastasis. It is important to control liver metastasis from PCG. 

PMID- 25963703
TI  - [A case of polymyositis associated with transverse colon cancer that responded to
      tumor resection and chemotherapy].
AB  - A 72-year-old woman was admitted to our hospital because of muscle weakness and
      was diagnosed as having polymyositis. Whole-body evaluation revealed advanced
      transverse colon cancer, and we therefore considered it likely that the patient
      had paraneoplastic myositis. We performed a curative surgical resection for colon
      cancer, after which her serum creatine phosphokinase(CPK)level greatly decreased.
      Steroid therapy was administered postoperatively. However, her CPK levels
      remained persistently high, even after steroid pulse therapy, and we considered
      that this was due to steroid-resistance myositis. We administered chemotherapy
      for colon cancer using 5-fluorouracil plus Leucovorin(5-FU/LV), after which the
      CPK levels gradually decreased. There have been few previous reports of
      polymyositis associated with colon cancer and a standard treatment for
      paraneoplastic myositis has not been established. Most clinicians believe that
      treatment of the primary tumor may contribute to an improvement of myositis, and
      in our case, tumor resection and chemotherapy were effective. 

PMID- 25963704
TI  - [A case of synchronous sigmoid cancer and ureter cancer].
AB  - A 78-year-old-man visited a nearby doctor for treatment of hepatitis C and high
      blood pressure.He was diagnosed with right hydronephrosis by abdominal echography
      conducted in follow-up of hepatitis C treatment in November 2011; he was then
      introduced to our hospital for close inspection and medical treatment.We observed
      wall hyperplasia and narrowing of the lumen in the central sigmoid part by
      contrast-enhanced computed tomography (CT).The right ureter at the L4/5 level
      showed wall hyperplasia and a deep color, and the right ureter, renal pelvis, and
      calix were expanded on the head side. By examination for CF, we observed a type 2
      lesion in the sigmoid colon, and a biopsy showed well-differentiated
      adenocarcinoma. Based upon these findings, he was diagnosed with synchronous
      sigmoid colon cancer (cT4aN0M0, cStage II) and ureter cancer (cT2N0M0, cStage
      II); we performed laparotomy sigmoidectomy(D3 dissection)and full extraction of
      the right kidney urinary tract (lymph node dissection in front of the vena cava,
      the latter outside and between the aorta and vena cava). The postoperative course
      was particularly uneventful, and the patient was discharged from the hospital on
      day 38 after the operation. More than 2 years after the surgery, the patient
      exhibits no sign of sigmoid colon cancer or ureter cancer recurrence.

PMID- 25963705
TI  - [Efficacy of a fentanyl citrate buccal tablet for esophageal cancer pain
      management in a patient unable to take oral medication].
AB  - We report a case ofa 60-year old male esophageal cancer patient who was unable to
      take oral medication, but was successfully treated using a fentanyl citrate
      buccal tablet. The patient survived a suicide attempt as a youth in which he
      ingested poison, but was left with a stricture of the esophagus. It became
      difficult for him to take nutrition orally, and he underwent an esophageal bypass
      operation, although he still required frequent endoscopic esophageal dilation. He
      subsequently presented with an anastomotic stenosis due to anastomotic leakage,
      and oral intake became completely impossible. The onset of esophageal cancer
      presented as corrosive esophagitis. We used oxycodone hydrochloride to treat a
      sharp pain resulting from cataplectic cancer in the jejunal tube, but this
      provided only limited pain relief. We therefore used a fentanyl citrate oral
      mucosa absorption preparation with a rescue agent, which did provide effective
      pain relief. Thus a fentanyl citrate buccal tablet could effectively relief pain
      in cancer patients who are unable to receive oral medication.

PMID- 25963706
TI  - Measuring and improving cardiopulmonary resuscitation quality inside the
      emergency department.
AB  - AIM OF STUDY: To evaluate CPR quality during cardiac resuscitation attempts in an
      urban emergency department (ED) and determine the influence of the combination of
      scenario-based training, real-time audiovisual feedback (RTAVF), and post-event
      debriefing on CPR quality. METHODS: CPR quality was recorded using an R Series
      monitor-defibrillator (ZOLL Medical) during the treatment of adult cardiac arrest
      patients. Phase 1 (P1; 11/01/2010-11/15/2012) was an observation period of CPR
      quality. Phase 2 (P2; 11/15/2012-11/08/2013) was after a 60-min psychomotor
      skills CPR training and included RTAVF and post-event debriefing. RESULTS: A
      total of 52 cardiac arrest patients were treated in P1 (median age 56 yrs, 63.5%
      male) and 49 in P2 (age 60 yrs, 83.7% male). Chest compression (CC) depth
      increased from 46.7 +/- 3.8mm in P1 to 61.6 +/- 2.8mm in P2 (p < 0.001), with the
      percentage of CC >= 51 mm increasing from 30.6% in P1 to 87.4% in P2 (p < 0.001).
      CC release velocity increased from 314 +/- 25 mm/s in P1 to 442 +/- 20 mm/s in P2
      (p < 0.001). No significant differences were identified in CC fraction (84.3% P1
      vs. 88.4% P2, p = 0.1), CC rate (125 +/- 3 cpm P1 vs. 125 +/- 3 cpm P2, p = 0.7),
      or pre-shock pause (9.7s P1 vs. 5.9s P2, p = 0.5), though CC fraction and pre
      shock pause were within guideline recommendations. CONCLUSION: Implementation of
      the bundle of scenario-based training, real-time audiovisual CPR feedback, and
      post-event debriefing was associated with improved CPR quality and compliance
      with CPR guidelines in this urban teaching emergency department.

PMID- 25963707
TI  - Reply to Letter: "Overestimated electrical exposure risk associated with hands-on
      defibrillation?".

PMID- 25963708
TI  - Epilepsy: Can fMRI predict memory decline after temporal lobe resection?

PMID- 25963709
TI  - Molecular anatomy of the thalamic complex and the underlying transcription
      factors.
AB  - Thalamocortical loops have been implicated in the control of higher-order
      cognitive functions, but advances in our understanding of the molecular
      underpinnings of neocortical organization have not been accompanied by similar
      analyses in the thalamus. Using expression-based correlation maps and the manual
      mapping of mouse and human datasets available in the Allen Brain Atlas, we
      identified a few individual regions and several sets of molecularly related
      nuclei that partially overlap with the classic grouping that is based on
      topographical localization and thalamocortical connections. These new molecular
      divisions of the adult thalamic complex are defined by the combinatorial
      expression of Tcf7l2, Lef1, Gbx2, Prox1, Pou4f1, Esrrg, and Six3 transcription
      factor genes. Further in silico and experimental analyses provided the evidence
      that TCF7L2 might be a pan-thalamic specifier. These results provide substantial
      insights into the "molecular logic" that underlies organization of the thalamic
      complex.

PMID- 25963710
TI  - Cortical reorganization in an astronaut's brain after long-duration spaceflight.
AB  - To date, hampered physiological function after exposure to microgravity has been
      primarily attributed to deprived peripheral neuro-sensory systems. For the first
      time, this study elucidates alterations in human brain function after long
      duration spaceflight. More specifically, we found significant differences in
      resting-state functional connectivity between motor cortex and cerebellum, as
      well as changes within the default mode network. In addition, the cosmonaut
      showed changes in the supplementary motor areas during a motor imagery task.
      These results highlight the underlying neural basis for the observed
      physiological deconditioning due to spaceflight and are relevant for future
      interplanetary missions and vestibular patients.

PMID- 25963711
TI  - Antitumour activity of 3-nitropropionic acid from Phomopsis sp. and optimization
      of fermentation conditions.
AB  - In this study, 3-nitropropionic acid (3-NPA) was separated and purified from
      endophytic fungi belonging to Phomopsis sp. and its cytotoxicity was determined
      by MTT assay. Treatment with 3-NPA for 24 h resulted in a dose-dependent
      apoptosis in MCF-7 cells. Through quantitative detection of the genes that are
      closely related to the Bcl-2 signalling pathway, there was an increased
      expression of p53 and Bax and a decreased expression of Bcl-2, which indicated
      apoptosis in these cells. Meanwhile, the overexpression of PARA (poly ADP-ribose
      polymerase) and apoptosis inducing factor (AIF) also suggested that 3-NPA induced
      cellular apoptosis through a caspase-3-independent pathway in caspase-3-deficient
      MCF-7 cells. The fermentation condition was also improved to produce more 3-NPA:
      glucose as a carbon source and yeast extract as a nitrogen source, fermentation
      for 8 days at 32 degrees C and a solution environment of pH 5.0. Under these
      conditions, the yield of 3-NPA was increased to 529 mg l(-1) compared with 410 mg
      l(-1) under traditional fermentation conditions. SIGNIFICANCE AND IMPACT OF THE
      STUDY: 3-Nitropropionic acid is a mitochondrial inhibitor and has some useful
      bioactivities such as antibacterial activity. In this paper we found that 3-NPA
      also has obvious cytotoxicity, so we studied its antitumour activity and tried to
      determine the antitumour molecular mechanism, opening a new perspective for
      potential antitumour prodrug development. As 3-NPA is often obtained from natural
      products with a low yield, in order to overcome the disadvantage of an endophytic
      fungi source of 3-NPA, we optimized the fermentation conditions for 3-NPA in
      Phomopsis sp. to obtain the maximum production of 3-NPA.

PMID- 25963712
TI  - Metacognition in First Episode Psychosis: Item Level Analysis of Associations
      with Symptoms and Engagement.
AB  - Significant metacognitive impairments are observed in first episode psychosis
      (FEP) and chronic psychosis samples. There is evidence of associations between
      metacognition and presentation in FEP, but the relative contribution of
      metacognitive understanding of the self and the other is as yet unclear. The
      current study is a secondary analysis of date on metacognition, symptoms and
      engagement with treatment (help-seeking) in an FEP sample. In a cross-sectional
      cohort study, individuals in the first 12 months of treatment metacognition were
      assessed with the Metacognition Assessment Scale-Revised version (MAS-R).
      Psychotic symptomatology and help-seeking within treatment (clinician-rated
      service engagement) were also measured. An item level analysis of the MAS-R was
      conducted exploring associations between symptoms and cognitive, emotional,
      differentiation, integration and decentration aspects of metacognition. We report
      that associations between negative symptoms and deficits in the understanding of
      other's mental states extend across cognitive, emotional, integrative and
      decentration aspects of metacognition. We also report associations between
      negative symptoms and understanding one's own mind. We also note that cognitive
      and decentration aspects of metacognition were significantly associated with help
      seeking once in treatment. Our findings suggest that an appreciation of
      metacognitive processes may inform treatment frameworks for FEP. Copyright (c)
      2015 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGES: Individual components of
      metacognition including the capacity to relate cognitive and emotional variables
      are important in first episode phychosis. Impaired metacognitive understanding of
      both one's own and others' mental states is associated with increased negative
      symptoms. Metacognitive variables may be important in understanding how different
      individuals seek help or engage with services after the initiation of treatment.

PMID- 25963713
TI  - [Epithelial neuroendocrine tumors of the upper respiratory tract: New entities,
      new perspectives].
AB  - Epithelial neuroendocrine tumors of the upper respiratory tract are rare and are
      classified as typical and atypical carcinoid versus small cell neuroendocrine
      carcinoma. Furthermore, a giant cell variant of neuroendocrine carcinoma is
      suggested corresponding to the bronchopulmonary system as well as a recently
      described subtype of oropharyngeal small cell neuroendocrine carcinoma associated
      with human papillomavirus. Many arguments relying on clinical as well as on
      molecular findings indicate that the distinction between carcinoid and poorly
      differentiated neuroendocrine carcinoma does not only reflect different degrees
      of differentiation of otherwise related tumors but indicates the existence of
      substantially different types of neoplasms. 

PMID- 25963714
TI  - Solithromycin to treat community-acquired pneumonia?

PMID- 25963715
TI  - Involvement of bone marrow cells and neuroinflammation in hypertension.
AB  - RATIONALE: Microglial activation in autonomic brain regions is a hallmark of
      neuroinflammation in neurogenic hypertension. Despite evidence that an impaired
      sympathetic nerve activity supplying the bone marrow (BM) increases inflammatory
      cells and decreases angiogenic cells, little is known about the reciprocal impact
      of BM-derived inflammatory cells on neuroinflammation in hypertension. OBJECTIVE:
      To test the hypothesis that proinflammatory BM cells from hypertensive animals
      contribute to neuroinflammation and hypertension via a brain-BM interaction.
      METHODS AND RESULTS: After BM ablation in spontaneously hypertensive rats, and
      reconstitution with normotensive Wistar Kyoto rat BM, the resultant chimeric
      spontaneously hypertensive rats displayed significant reduction in mean arterial
      pressure associated with attenuation of both central and peripheral inflammation.
      In contrast, an elevated mean arterial pressure along with increased central and
      peripheral inflammation was observed in chimeric Wistar-Kyoto rats reconstituted
      with spontaneously hypertensive rat BM. Oral treatment with minocycline, an
      inhibitor of microglial activation, attenuated hypertension in both the
      spontaneously hypertensive rats and the chronic angiotensin II-infused rats. This
      was accompanied by decreased sympathetic drive and inflammation. Furthermore, in
      chronic angiotensin II-infused rats, minocycline prevented extravasation of BM
      derived cells to the hypothalamic paraventricular nucleus, presumably via a
      mechanism of decreased C-C chemokine ligand 2 levels in the cerebrospinal fluid.
      CONCLUSIONS: The BM contributes to hypertension by increasing peripheral
      inflammatory cells and their extravasation into the brain. Minocycline is an
      effective therapy to modify neurogenic components of hypertension. These
      observations support the hypothesis that BM-derived cells are involved in
      neuroinflammation, and targeting them may be an innovative strategy for
      neurogenic resistant hypertension therapy.

PMID- 25963716
TI  - Deficiency of MMP17/MT4-MMP proteolytic activity predisposes to aortic aneurysm
      in mice.
AB  - RATIONALE: Aortic dissection or rupture resulting from aneurysm causes 1% to 2%
      of deaths in developed countries. These disorders are associated with mutations
      in genes that affect vascular smooth muscle cell differentiation and
      contractility or extracellular matrix composition and assembly. However, as many
      as 75% of patients with a family history of aortic aneurysms do not have an
      identified genetic syndrome. OBJECTIVE: To determine the role of the protease
      MMP17/MT4-MMP in the arterial wall and its possible relevance in human aortic
      pathology. METHODS AND RESULTS: Screening of patients with inherited thoracic
      aortic aneurysms and dissections identified a missense mutation (R373H) in the
      MMP17 gene that prevented the expression of the protease in human transfected
      cells. Using a loss-of-function genetic mouse model, we demonstrated that the
      lack of Mmp17 resulted in the presence of dysfunctional vascular smooth muscle
      cells and altered extracellular matrix in the vessel wall; and it led to
      increased susceptibility to angiotensin-II-induced thoracic aortic aneurysm. We
      also showed that Mmp17-mediated osteopontin cleavage regulated vascular smooth
      muscle cell maturation via c-Jun N-terminal kinase signaling during aorta wall
      development. Some features of the arterial phenotype were prevented by re
      expression of catalytically active Mmp17 or the N-terminal osteopontin fragment
      in Mmp17-null neonates. CONCLUSIONS: Mmp17 proteolytic activity regulates
      vascular smooth muscle cell phenotype in the arterial vessel wall, and its
      absence predisposes to thoracic aortic aneurysm in mice. The rescue of part of
      the vessel-wall phenotype by a lentiviral strategy opens avenues for therapeutic
      intervention in these life-threatening disorders.

PMID- 25963717
TI  - mRNA expression levels of hypoxia-induced and stem cell-associated genes in human
      glioblastoma.
AB  - The roles of hypoxia-induced and stem cell-associated genes in the development of
      malignancy and tumour progression are well known. However, there are a limited
      number of studies analysing the impact of mRNA expression levels of hypoxia
      induced and stem cell-associated genes in the tissues of brain tumours and
      glioblastoma patients. In this study, tumour tissues from patients with
      glioblastoma multiforme and tumour adjacent tissues were analysed. We
      investigated mRNA expression levels of hypoxia-inducible factor-1alpha (HIF
      1alpha), hypoxia-inducible factor-2alpha (HIF-2alpha), carbonic anhydrase 9
      (CA9), vascular endothelial growth factor (VEGF), glucose transporter-1 (GLUT-1)
      and osteopontin (OPN), and stem cell-associated genes survivin, epidermal growth
      factor receptor (EGFR), human telomerase reverse transcriptase (hTERT), Nanog and
      octamer binding transcription factor 4 (OCT4) using quantitative real-time
      polymerase chain reaction (qRT-PCR). Our data revealed higher mRNA expression
      levels of hypoxia-induced and stem cell-associated genes in tumour tissue than
      levels in the tumour adjacent tissues in patients with glioblastoma multiforme. A
      strong positive correlation between the mRNA expression levels of HIF-2alpha,
      CA9, VEGF, GLUT-1 and OPN suggests a specific hypoxia-associated profile of mRNA
      expression in glioblastoma multiforme. Additionally, the results indicate the
      role of stem-cell-related genes in tumour hypoxia. Kaplan-Maier analysis revealed
      that high mRNA expression levels of hypoxia-induced markers showed a trend
      towards shorter overall survival in glioblastoma patients (P=0.061). Our data
      suggest that mRNA expression levels of hypoxia-induced genes are important tumour
      markers in patients with glioblastoma multiforme.

PMID- 25963718
TI  - Phytase activity in lichens.
AB  - Phytase activity was investigated in 13 lichen species using a novel assay
      method. The work tested the hypothesis that phytase is a component of the suite
      of surface-bound lichen enzymes that hydrolyse simple organic forms of phosphorus
      (P) and nitrogen (N) deposited onto the thallus surface. Hydrolysis of inositol
      hexaphosphate (InsP6 , the substrate for phytase) and appearance of lower-order
      inositol phosphates (InsP5 -InsP1 ), the hydrolysis products, were measured by
      ion chromatography. Phytase activity in Evernia prunastri was compared among
      locations with contrasting rates of N deposition. Phytase activity was readily
      measurable in epiphytic lichens (e.g. 11.3 MUmol InsP6 hydrolysed g(-1)  h(-1) in
      Bryoria fuscescens) but low in two terricolous species tested (Cladonia
      portentosa and Peltigera membranacea). Phytase and phosphomonoesterase activities
      were positively correlated amongst species. In E. prunastri both enzyme
      activities were promoted by N enrichment and phytase activity was readily
      released into thallus washings. InsP6 was not detected in tree canopy throughfall
      but was present in pollen leachate. Capacity to hydrolyse InsP6 appears
      widespread amongst lichens potentially promoting P capture from atmospheric
      deposits and plant leachates, and P cycling in forest canopies. The enzyme assay
      used here might find wider application in studies on plant root-fungal-soil
      systems. 

PMID- 25963719
TI  - Analysis of linear measurements on 3D surface models using CBCT data segmentation
      obtained by automatic standard pre-set thresholds in two segmentation software
      programs: an in vitro study.
AB  - OBJECTIVE: The aim of this in vitro study was to evaluate the reliability and
      accuracy of linear measurements on three-dimensional (3D) surface models obtained
      by standard pre-set thresholds in two segmentation software programs. MATERIALS
      AND METHODS: Ten mandibles with 17 silica markers were scanned for 0.3-mm voxels
      in the i-CAT Classic (Imaging Sciences International, Hatfield, PA, USA). Twenty
      linear measurements were carried out by two observers two times on the 3D surface
      models: the Dolphin Imaging 11.5 (Dolphin Imaging & Management Solutions,
      Chatsworth, CA, USA), using two filters(Translucent and Solid-1), and in the
      InVesalius 3.0.0 (Centre for Information Technology Renato Archer, Campinas, SP,
      Brazil). The physical measurements were made by another observer two times using
      a digital caliper on the dry mandibles. RESULTS: Excellent intra- and inter
      observer reliability for the markers, physical measurements, and 3D surface
      models were found (intra-class correlation coefficient (ICC) and Pearson's r >=
      0.91). The linear measurements on 3D surface models by Dolphin and InVesalius
      software programs were accurate (Dolphin Solid-1 > InVesalius > Dolphin
      Translucent). The highest absolute and percentage errors were obtained for the
      variable R1-R1 (1.37 mm) and MF-AC (2.53 %) in the Dolphin Translucent and
      InVesalius software, respectively. CONCLUSION: Linear measurements on 3D surface
      models obtained by standard pre-set thresholds in the Dolphin and InVesalius
      software programs are reliable and accurate compared with physical measurements.
      CLINICAL RELEVANCE: Studies that evaluate the reliability and accuracy of the 3D
      models are necessary to ensure error predictability and to establish diagnosis,
      treatment plan, and prognosis in a more realistic way.

PMID- 25963720
TI  - Oral rehabilitation with dental implants and quality of life following mandibular
      reconstruction with free fibular flap.
AB  - OBJECTIVES: Bony reconstruction of jaw defects using the free fibular flap and
      dental rehabilitation mostly requires insertion of dental implants within the
      transferred fibula bone. The aim of this paper was to discuss results of the
      implant stability with data on the possible benefit for the patient's quality of
      life after such treatment. MATERIAL AND METHODS: For clinical outcome of
      implants, we evaluated 26 patients with a total number of 94 dental implants
      after a follow-up period of 12 to 132 months. A group of 38 patients who
      underwent mandibular reconstruction with free fibular flap could be included in
      the life-quality study. Evaluation included 23 patients with and 15 patients
      without implant-borne restoration. The quality of life was assessed using the
      standard QLQ C-30 questionnaire and the H&N35 module of the European Organisation
      for Research and Treatment of Cancer (EORTC). RESULTS: Of implants, 94.7 % were
      stable at the time of investigation and could be used for prosthesis. Patients
      with dental implants reported improvement of life quality along with better
      scores in most function and symptom scales; however, only values for global
      health status (QL2), absence of dyspnea (DY) and absence of feeding tube (HNFE)
      were significantly better than in the control group. CONCLUSION: Dental implant
      insertion in fibula grafts along with implant-borne restoration is a proven
      concept and might lead to improved quality of life following ablative surgery of
      the jaw. The effect on the quality of life is not as predictable as on the
      implant stability. CLINICAL RELEVANCE: Patients with bony defects of the jaw
      require bony reconstruction. This allows further masticatory rehabilitation using
      dental implants and might lead to improved quality of life.

PMID- 25963721
TI  - A comparison between two negative pressure irrigation techniques in simulated
      immature tooth: an ex vivo study.
AB  - OBJECTIVES: This ex vivo study evaluated the irrigation efficacy of a new apical
      negative pressure system (ANP) in canals with simulated immature teeth, by
      comparing it to EndoVac (EV) system in terms of smear layer (SL) removal and
      irrigation extrusion. MATERIALS AND METHODS: Three millimetres of the root end of
      40 single canalled lower incisors were resected and decoronated to standardize
      root canal length. After instrumentation, the specimens were embedded in warm
      normal saline agar coloured with 1 % acid red and randomly divided into four
      groups; one control group and three experimental groups. Except in the control
      group where distilled water was used as irrigant using positive pressure
      irrigation needle, the canals were irrigated with 6 % NaOCl and 17 % EDTA using
      the intracanal negative pressure needle (iNP) system, the EV system or 27G open
      ended needle under positive pressure (PP). NaOCl extrusion was determined by
      observing a discolouration of the agar surrounding the root. The SL was evaluated
      by observing scanning electron microscope images based on a four-level scoring
      system. RESULTS: Two specimens with irrigant extrusion were observed in the iNP
      group, which was significantly different (logistic regression, p < 0.05) to EV
      and PP. There were no significant differences (Kruskall-Wallis test, p > 0.05)
      among the experimental groups in terms of SL removal, but all were significantly
      different to the control group. CONCLUSIONS: Irrigation with the iNP could be a
      viable alternative to EV as an apical negative pressure irrigation technique
      especially while treating immature teeth. CLINICAL RELEVANCE: ANP in canal
      cleanliness is recommended to be utilized in treating immature teeth where
      periapical tissues should be saved and stimulated. The iNP system might have the
      potential to avoid irrigant extrusion while cleaning the canal till the apical
      end.

PMID- 25963722
TI  - Dose-dependent suppression of human photoparoxysmal response with the competitive
      AMPA/kainate receptor antagonist BGG492: Clear PK/PD relationship.
AB  - OBJECTIVE: Examine the efficacy of a competitive alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA)/kainate glutamate receptor antagonist,
      selurampanel (BGG492), in the human photostimulation model. METHODS: Patients
      with epilepsy and a generalized epileptiform electroencephalography response to
      intermittent photic stimulation (photoparoxysmal response or PPR; diagnosed >= 6
      months prior to initial study dosing) were enrolled in a phase II, multicenter,
      single-blind, within-subject, placebo-controlled proof-of-concept (PoC) study.
      PPR was used as a biomarker to assess the efficacy and safety of BGG492 in three
      cohorts (cohorts I-III received BGG492 50, 100, and 15 mg, respectively). Primary
      endpoints were to evaluate the efficacy of single oral BGG492 doses in
      abolishment of PPR or a relevant reduction of the standardized photoparoxysmal
      response (SPR), and to evaluate time of onset and duration of response. Secondary
      endpoints were to evaluate maximal SPR reduction, determine the pharmacokinetic
      profile of BGG492, explore the pharmacokinetic/pharmacodynamic relationship, and
      evaluate the safety and tolerability of BGG492. RESULTS: Ten patients were
      enrolled, with three participating twice, that is, in two cohorts (n = 13).
      Treatment with BGG492 resulted in abolition of PPR in seven of 13 patients in a
      dose-dependent manner: three, three, and one patient in cohorts I-III,
      respectively. All patients showed treatment-related reductions of SPR range of at
      least three steps in at least one eye condition (eye closure, eyes closed, or
      eyes open). Generally, onset of the suppressive effect appeared to be within 1-2
      h post-BGG492 dose and continued in three patients at the 50- and 100-mg doses
      for 29-33 h. Most common adverse events across the BGG492-treated groups were
      headache and nasopharyngitis (three patients each), followed by dizziness,
      fatigue, and diarrhea (two patients each). SIGNIFICANCE: The dose-dependent
      positive effect of BGG492 on the PPR and SPR in patients with photosensitive
      epilepsy in this proof-of-concept study supports further investigation of AMPA
      receptor antagonists in large-scale phase III trials.

PMID- 25963725
TI  - Failed Pediatric Drug Development Trials.
AB  - Pediatric product development initiatives have stimulated the development of
      therapies for children, resulting in improved product labeling, increased
      identification of adverse events, and development of new pediatric formulations.
      However, 42% of recently completed pediatric trials have failed to establish
      either safety or efficacy, leading to an inability to label the product for use
      in children.(1) Characterizing these failed trials, including common contributing
      factors, is imperative to designing better pediatric trials in the future. 

PMID- 25963724
TI  - Chronic social isolation during adolescence augments catecholamine response to
      acute ethanol in the basolateral amygdala.
AB  - Adolescent social isolation (SI) results in numerous behavioral alterations
      associated with increased risk of alcoholism. Notably, many of these changes
      involve the basolateral amygdala (BLA), including increased alcohol seeking. The
      BLA sends a strong glutamatergic projection to the nucleus accumbens and
      activation of this pathway potentiates reward-seeking behavior. Dopamine (DA) and
      norepinephrine (NE) exert powerful excitatory and inhibitory effects on BLA
      activity and chronic stress can disrupt the excitation-inhibition balance
      maintained by these catecholamines. Notably, the impact of SI on BLA DA and NE
      neurotransmission is unknown. Thus the aim of this study was to characterize SI
      mediated catecholamine alterations in the BLA. Male Long Evans rats were housed
      in groups of four (GH) or in SI for 6 weeks during adolescence. DA and NE
      transporter levels were then measured using Western blot hybridization and
      baseline and ethanol-stimulated DA and NE levels were quantified using
      microdialysis. DA transporter levels were increased and baseline DA levels were
      decreased in SI compared to GH rats. SI also increased DA responses to an acute
      ethanol (2 g kg(-1)) challenge. While no group differences were noted in NE
      transporter or baseline NE levels, acute ethanol (2 g kg(-1)) only significantly
      increased NE levels in SI animals. Collectively, these SI-dependent changes in
      BLA catecholamine signaling may lead to an increase in BLA excitability and a
      strengthening of the glutamatergic projection between the BLA and NAc. Such
      changes may promote the elevated ethanol drinking behavior observed in rats
      subjected to chronic adolescent stress.

PMID- 25963726
TI  - Treatment with Iodine in Pregnant Rats with Marginal Iodine Deficiency Improves
      Cell Migration in the Developing Brain of the Progeny.
AB  - Marginal iodine deficiency is a common health problem in pregnant women.
      Epidemiological and animal studies had shown that marginally maternal iodine
      deficiency could cause the mild changes of maternal thyroid function, eventually
      lead to a negative effect on neurodevelopment. But the underlying mechanisms
      responsible for the neurological impairment remain unclear. The aim of this study
      is to explore whether marginally maternal iodine deficiency could produce subtle
      changes in cell migration and cognitive function of offspring, and the optimal
      time of giving intervention to minimize the adverse effects. In the present
      study, we established a marginal iodine deficiency model, and iodine supplement
      was performed on pre-pregnancy (PP), G13 (gestation day 13), and postnatal day 0
      (P0). Our data showed that there were changes in the cytoarchitecture and the
      percentage of bromodeoxyuridine (BrdU)-labeled cells in the cerebral cortex in
      marginal iodine deficiency rats. The Reelin expression was significantly lower,
      but Tenascin-C was higher in the cerebral cortex of marginal iodine deficiency
      group on P7 than the normal group, respectively. When iodine supplement,
      especially before G13 could reverse the abnormal expression of the two proteins
      involved in cell migration, which was consistent with the results of Morris Water
      Maze test. The three intervention groups had shorter escape latencies than the
      marginal iodine deficiency rats. The earlier that iodine is supplied, the better
      behavior performance would reach. Our findings suggested that iodine supplement
      in early stage of pregnancy could improve the cell migration of cerebral cortex
      and neurodevelopment of offspring. 

PMID- 25963727
TI  - Metabolomic Analysis Reveals Increased Aerobic Glycolysis and Amino Acid Deficit
      in a Cellular Model of Amyotrophic Lateral Sclerosis.
AB  - Defects in energy metabolism are potential pathogenic mechanisms in amyotrophic
      lateral sclerosis (ALS), a rapidly fatal disease with no cure. The mechanisms
      through which this occurs remain elusive and their understanding may prove
      therapeutically useful. We used metabolomics and stable isotope tracers to
      examine metabolic changes in a well-characterized cell model of familial ALS, the
      motor neuronal NSC-34 line stably expressing human wild-type Cu/Zn superoxide
      dismutase (wtSOD1) or mutant G93A (G93ASOD1). Our findings indicate that wt and
      G93ASOD1 expression both enhanced glucose metabolism under serum deprivation.
      However, in wtSOD1 cells, this phenotype increased supply of amino acids for
      protein and glutathione synthesis, while in G93ASOD1 cells it was associated with
      death, aerobic glycolysis, and a broad dysregulation of amino acid homeostasis.
      Aerobic glycolysis was mainly due to induction of pyruvate dehydrogenase kinase
      1. Our study thus provides novel insight into the role of deranged energy
      metabolism as a cause of poor adaptation to stress and a promoter of neural cell
      damage in the presence of mutant SOD1. Furthermore, the metabolic alterations we
      report may help explain why mitochondrial dysfunction and impairment of the
      endoplasmic reticulum stress response are frequently seen in ALS. 

PMID- 25963728
TI  - Maternal Thyroxine Levels During Pregnancy and Outcomes of Cognitive Development
      in Children.
AB  - Though there were many studies assessing the relationship between maternal
      thyroxine levels during pregnancy and cognitive development in children, there
      was still lack of evidence for the association from a comprehensive assessment of
      published data. To get a more comprehensive estimate of the influence of low
      maternal thyroxine levels on cognitive function, a meta-analysis of prospective
      cohort studies was performed. Two electronic databases, MEDLINE and EMBASE, were
      searched for relevant prospective cohort studies. Relative risks (RR) with 95%
      confidence intervals (95% CI) were pooled using random-effect model of meta
      analysis to assess the risk of delayed cognitive development in children. Seven
      prospective cohort studies with a total of 8273 mother-child pairs were included
      into the meta-analysis. There was obvious between-study heterogeneity in the meta
      analysis (I(2) = 69.6%). Meta-analysis of using random-effect model showed that
      low maternal thyroxine level was significantly associated with a threefold risk
      of delayed cognitive development in children (random RR = 3.08, 95% CI 1.83-5.18,
      P < 0.001). When excluding the study with largest weight, there was no obvious
      between-study heterogeneity in the left studies (I(2) = 47.6%), and meta-analysis
      using random-effect model showed that low maternal thyroxine level was still
      significantly associated with increased risk of delayed cognitive development in
      children (random RR = 3.76, 95% CI 2.14-6.58, P < 0.001). Sensitivity analysis by
      omitting other studies by turns showed that there was no obvious change in the
      pooled risk estimates, and all pooled RRs were statistically significant.
      Therefore, the findings from the meta-analysis provide strong evidence for the
      association between maternal thyroxine levels during pregnancy and cognitive
      development in children. Low maternal thyroxine level is significantly associated
      with a threefold risk of delayed cognitive development in children.

PMID- 25963730
TI  - Staged treatment of a chronic patellar sleeve fracture using the Taylor spatial
      frame.
AB  - Patellar sleeve fractures are easily missed injuries since plain radiographs may
      not show a bony fragment at the time of injury. Failure to diagnose these
      injuries can result in patellar instability, extensor lag, and anterior knee
      pain. We report a novel treatment using a Taylor spatial frame as part of a
      staged reconstruction to regain length of the extensor mechanism and maintain
      knee motion prior to performing primary repair of the avulsed patellar sleeve
      fragment. In our case, an 11-year-old male presented to our institution six
      months after sustaining a patellar sleeve fracture. Radiographic examination with
      the knee in extension revealed a 23-mm gap between the inferior patellar pole
      fragment and the remaining patella. The patient was ultimately taken to the
      operating room twelve months after the initial injury for placement of a Taylor
      spatial frame to regain length of the extensor mechanism. The patient began
      immediate knee range-of-motion exercises, and performed daily soft tissue
      lengthening of two millimeters. After four weeks of treatment the patient
      underwent removal of the fixator and primary repair of the patella. At final
      follow up six years after patellar reconstruction, the patient had an active knee
      range-of-motion from five degrees of hyperextension to 140 degrees  of flexion.
      Where current literature reports suboptimal results even when treatment is
      delayed for two months, in our case the patient was able to obtain a high level
      of function after treatment with a two-stage reconstruction using a Taylor
      spatial frame. 

PMID- 25963729
TI  - Bisphenol-A Mediated Inhibition of Hippocampal Neurogenesis Attenuated by
      Curcumin via Canonical Wnt Pathway.
AB  - Bisphenol A (BPA) is an environmental xenoestrogenic endocrine disruptor,
      utilized for production of consumer products, and exerts adverse effects on the
      developing nervous system. Recently, we found that BPA impairs the finely tuned
      dynamic processes of neurogenesis (generation of new neurons) in the hippocampus
      of the developing rat brain. Curcumin is a natural polyphenolic compound, which
      provides neuroprotection against various environmental neurotoxicants and in the
      cellular and animal models of neurodegenerative disorders. Here, we have assessed
      the neuroprotective efficacy of curcumin against BPA-mediated reduced
      neurogenesis and the underlying cellular and molecular mechanism(s). Both in
      vitro and in vivo studies showed that curcumin protects against BPA-induced
      hippocampal neurotoxicity. Curcumin protects against BPA-mediated reduced neural
      stem cells (NSC) proliferation and neuronal differentiation and enhanced
      neurodegeneration. Curcumin also enhances the expression/levels of neurogenic and
      the Wnt pathway genes/proteins, which were reduced due to BPA exposure in the
      hippocampus. Curcumin-mediated neuroprotection against BPA-induced neurotoxicity
      involved activation of the Wnt/beta-catenin signaling pathway, which was
      confirmed by the use of Wnt specific activators (LiCl and GSK-3beta siRNA) and
      inhibitor (Dkk-1). BPA-mediated increased beta-catenin phosphorylation, decreased
      GSK-3beta levels, and beta-catenin nuclear translocation were significantly
      reversed by curcumin, leading to enhanced neurogenesis. Curcumin-induced
      protective effects on neurogenesis were blocked by Dkk-1 in NSC culture treated
      with BPA. Curcumin-mediated enhanced neurogenesis was correlated well with
      improved learning and memory in BPA-treated rats. Overall, our results conclude
      that curcumin provides neuroprotection against BPA-mediated impaired neurogenesis
      via activation of the Wnt/beta-catenin signaling pathway.

PMID- 25963732
TI  - In Vitro and In Vivo Evaluation of Whitlockite Biocompatibility: Comparative
      Study with Hydroxyapatite and beta-Tricalcium Phosphate.
AB  - Biomimicking ceramics have been developed to induce efficient recovery of damaged
      hard tissues. Among them, calcium phosphate-based bioceramics have been the most
      widely used because of their similar composition with human hard tissue and
      excellent biocompatibilities. However, the incomplete understanding of entire
      inorganic phases in natural bone has limited the recreation of complete bone
      compositions. In this work, broad biomedical evaluation of whitlockite (WH:
      Ca18Mg2(HPO4)2(PO4)12), which is the secondary inorganic phase in bone, is
      conducted to better understand human hard tissue and to seek potential
      application as a biomaterial. Based on the recently developed gram-scale method
      for synthesizing WH nanoparticles, the properties of WH as a material for
      cellular scaffolding and bone implants are assessed and compared to those of
      hydroxyapatite (HAP: Ca10(PO4)6(OH)2) and beta-tricalcium phosphate (beta-TCP:
      beta-Ca3(PO4)2). WH-reinforced composite scaffolds facilitate bone-specific
      differentiation compared to HAP-reinforced composite scaffolds. Additionally, WH
      implants induce similar or better bone regeneration in calvarial defects in a rat
      model compared to HAP and beta-TCP implants, with intermediate resorbability. New
      findings of the properties of WH that distinguish it from HAP and beta-TCP are
      significant in understanding human hard tissue, mimicking bone tissue at the
      nanoscale and designing functional bioceramics.

PMID- 25963735
TI  - Delivery balloon-induced ascending aortic dissection: An unusual complication
      during transcatheter aortic valve implantation.
AB  - Transcatheter aortic valve implantation (TAVI) is a relatively mature technique
      that is generally accepted as a promising treatment for inoperable patients and
      those who are high-risk candidates for surgical aortic replacement. Although
      severe complications in the aortic valve complex, such as annular or aortic root
      rupture, are not frequently observed, these events could easily lead to
      catastrophic outcomes, and therefore remain major issues during TAVI. However,
      there remains a paucity of data describing these catastrophic complications
      because of their low incidence. We encountered the case of an 88-year-old woman
      complicated by a dissection of the ascending aorta during TAVI from an "unusual"
      cause: injury due to the delivery of a balloon-expandable valve to a very narrow
      and heavily calcified sinotubular junction (STJ). This is the first report to
      demonstrate the mechanism of this complication; even a delivery balloon, not a
      stent frame, with low inflation pressure might injure a narrow STJ and lead to an
      aortic dissection. Therefore, the use of oversized delivery balloons should be
      avoided in patients with a narrow and calcified STJ. (c) 2015 Wiley Periodicals,
      Inc.

PMID- 25963733
TI  - Functional connectivity of the dorsal and median raphe nuclei at rest.
AB  - Serotonin (5-HT) is a neurotransmitter critically involved in a broad range of
      brain functions and implicated in the pathophysiology of neuropsychiatric
      illnesses including major depression, anxiety and sleep disorders. Despite being
      widely distributed throughout the brain, there is limited knowledge on the
      contribution of 5-HT to intrinsic brain activity. The dorsal raphe (DR) and
      median raphe (MR) nuclei are the source of most serotonergic neurons projecting
      throughout the brain and thus provide a compelling target for a seed-based probe
      of resting-state activity related to 5-HT. Here we implemented a novel multimodal
      neuroimaging approach for investigating resting-state functional connectivity
      (FC) between DR and MR and cortical, subcortical and cerebellar target areas.
      Using [(11)C]DASB positron emission tomography (PET) images of the brain
      serotonin transporter (5-HTT) combined with structural MRI from 49 healthy
      volunteers, we delineated DR and MR and performed a seed-based resting-state FC
      analysis. The DR and MR seeds produced largely similar FC maps: significant
      positive FC with brain regions involved in cognitive and emotion processing
      including anterior cingulate, amygdala, insula, hippocampus, thalamus, basal
      ganglia and cerebellum. Significant negative FC was observed within pre- and
      postcentral gyri for the DR but not for the MR seed. We observed a significant
      association between DR and MR FC and regional 5-HTT binding. Our results provide
      evidence for a resting-state network related to DR and MR and comprising regions
      receiving serotonergic innervation and centrally involved in 5-HT related
      behaviors including emotion, cognition and reward processing. These findings
      provide a novel advance in estimating resting-state FC related to 5-HT signaling,
      which can benefit our understanding of its role in behavior and neuropsychiatric
      illnesses. 

PMID- 25963736
TI  - Biological characterization of stage I follicular lymphoma according to
      extranodal or nodal primary origin and t(14;18) status using high-resolution
      array-based comparative genomic hybridization.

PMID- 25963737
TI  - The structure of FMNL2-Cdc42 yields insights into the mechanism of lamellipodia
      and filopodia formation.
AB  - Formins are actin polymerization factors that elongate unbranched actin filaments
      at the barbed end. Rho family GTPases activate Diaphanous-related formins through
      the relief of an autoregulatory interaction. The crystal structures of the N
      terminal domains of human FMNL1 and FMNL2 in complex with active Cdc42 show that
      Cdc42 mediates contacts with all five armadillo repeats of the formin with
      specific interactions formed by the Rho-GTPase insert helix. Mutation of three
      residues within Rac1 results in a gain-of-function mutation for FMNL2 binding and
      reconstitution of the Cdc42 phenotype in vivo. Dimerization of FMNL1 through a
      parallel coiled coil segment leads to formation of an umbrella-shaped structure
      that-together with Cdc42-spans more than 15 nm in diameter. The two interacting
      FMNL-Cdc42 heterodimers expose six membrane interaction motifs on a convex
      protein surface, the assembly of which may facilitate actin filament elongation
      at the leading edge of lamellipodia and filopodia.

PMID- 25963739
TI  - Gradual Retirement in the Netherlands: An Analysis Using Administrative Data.
AB  - Gradual retirement by which individuals leave their career jobs and withdraw
      incrementally from the labor force is an important empirical phenomenon in the
      United States. We analyze the current state of gradual retirement in the
      Netherlands using administrative data that allow much more precise tracking of
      labor market transitions than most survey panel data. We estimate multinomial
      transition models, taking into account competing pathways out of career
      employment at older ages, and discuss institutional aspects that limit the scope
      of gradual retirement, such as financial incentives to retire early. 

PMID- 25963738
TI  - Diploid males support a two-step mechanism of endosymbiont-induced thelytoky in a
      parasitoid wasp.
AB  - BACKGROUND: Haplodiploidy, where females develop from diploid, fertilized eggs
      and males from haploid, unfertilized eggs, is abundant in some insect lineages.
      Some species in these lineages reproduce by thelytoky that is caused by infection
      with endosymbionts: infected females lay haploid eggs that undergo diploidization
      and develop into females, while males are very rare or absent. It is generally
      assumed that in thelytokous wasps, endosymbionts merely diploidize the
      unfertilized eggs, which would then trigger female development. RESULTS: We found
      that females in the parasitoid wasp Asobara japonica infected with thelytoky
      inducing Wolbachia produce 0.7-1.2% male offspring. Seven to 39% of these males
      are diploid, indicating that diploidization and female development can be
      uncoupled in A. japonica. Wolbachia titer in adults was correlated with their
      ploidy and sex: diploids carried much higher Wolbachia titers than haploids, and
      diploid females carried more Wolbachia than diploid males. Data from
      introgression lines indicated that the development of diploid individuals into
      males instead of females is not caused by malfunction-mutations in the host
      genome but that diploid males are most likely produced when the endosymbiont
      fails to activate the female sex determination pathway. Our data therefore
      support a two-step mechanism by which endosymbionts induce thelytoky in A.
      japonica: diploidization of the unfertilized egg is followed by feminization,
      whereby each step correlates with a threshold of endosymbiont titer during wasp
      development. CONCLUSIONS: Our new model of endosymbiont-induced thelytoky
      overthrows the view that certain sex determination mechanisms constrain the
      evolution of endosymbiont-induced thelytoky in hymenopteran insects.
      Endosymbionts can cause parthenogenesis through feminization, even in groups in
      which endosymbiont-diploidized eggs would develop into males following the hosts'
      sex determination mechanism. In addition, our model broadens our understanding of
      the mechanisms by which endosymbionts induce thelytoky to enhance their
      transmission to the next generation. Importantly, it also provides a novel window
      to study the yet-poorly known haplodiploid sex determination mechanisms in
      haplodiploid insects.

PMID- 25963734
TI  - Regional flux analysis for discovering and quantifying anatomical changes: An
      application to the brain morphometry in Alzheimer's disease.
AB  - In this study we introduce the regional flux analysis, a novel approach to
      deformation based morphometry based on the Helmholtz decomposition of
      deformations parameterized by stationary velocity fields. We use the scalar
      pressure map associated to the irrotational component of the deformation to
      discover the critical regions of volume change. These regions are used to
      consistently quantify the associated measure of volume change by the
      probabilistic integration of the flux of the longitudinal deformations across the
      boundaries. The presented framework unifies voxel-based and regional approaches,
      and robustly describes the volume changes at both group-wise and subject-specific
      level as a spatial process governed by consistently defined regions. Our
      experiments on the large cohorts of the ADNI dataset show that the regional flux
      analysis is a powerful and flexible instrument for the study of Alzheimer's
      disease in a wide range of scenarios: cross-sectional deformation based
      morphometry, longitudinal discovery and quantification of group-wise volume
      changes, and statistically powered and robust quantification of hippocampal and
      ventricular atrophy. 

PMID- 25963740
TI  - Pathway-based personalized analysis of breast cancer expression data.
AB  - INTRODUCTION: Most analyses of high throughput cancer data represent tumors by
      "atomistic" single-gene properties. Pathifier, a recently introduced method,
      characterizes a tumor in terms of "coarse grained" pathway-based variables.
      METHODS: We applied Pathifier to study a very large dataset of 2000 breast cancer
      samples and 144 normal tissues. Pathifier uses known gene assignments to pathways
      and biological processes to calculate for each pathway and tumor a Pathway
      Deregulation Score (PDS). Individual samples are represented in terms of their
      PDSs calculated for several hundred pathways, and the samples of the data set are
      analyzed and stratified on the basis of their profiles over these "coarse
      grained", biologically meaningful variables. RESULTS: We identified nine tumor
      subtypes; a new subclass (comprising about 7% of the samples) exhibits high
      deregulation in 38 PKA pathways, induced by overexpression of the gene PRKACB.
      Another interesting finding is that basal tumors break into two subclasses, with
      low and high deregulation of a cluster of immune system pathways. High
      deregulation corresponds to higher concentrations of Tumor Infiltrating
      Lymphocytes, and the patients of this basal subtype have better prognosis. The
      analysis used 1000 "discovery set" tumors; our results were highly reproducible
      on 1000 independent "validation" samples. CONCLUSIONS: The coarse-grained
      variables that represent pathway deregulation provide a basis for relevant, novel
      and robust findings for breast cancer. Our analysis indicates that in breast
      cancer reliable prognostic signatures are most likely to be obtained by treating
      separately different subgroups of the patients.

PMID- 25963742
TI  - CYP2E1 epigenetic regulation in chronic, low-level toluene exposure: Relationship
      with oxidative stress and smoking habit.
AB  - BACKGROUND: CYP2E1 is a versatile phase I drug-metabolizing enzyme responsible
      for the biotransformation of most volatile organic compounds, including toluene.
      Human toluene exposure increases CYP2E1 mRNA and modifies its activity in
      leucocytes; however, epigenetic implications of this interaction have not been
      investigated. GOAL: To determine promoter methylation of CYP2E1 and other genes
      known to be affected by toluene exposure. METHODS: We obtained venous blood from
      24 tannery workers exposed to toluene (mean levels: 10.86+/-7mg/m(3)) and 24
      administrative workers (reference group, mean levels 0.21+/-0.02mg/m(3)) all of
      them from the city of Leon, Guanajuato, Mexico. After DNA extraction and
      bisulfite treatment, we performed PCR-pyrosequencing in order to measure
      methylation levels at promoter region of 13 genes. RESULTS: In exposed group we
      found significant correlations between toluene airborne levels and CYP2E1
      promoter methylation (r=-.36, p<0.05), as well as for IL6 promoter methylation
      levels (r=.44, p<0.05). Moreover, CYP2E1 promoter methylation levels where higher
      in toluene-exposed smokers compared to nonsmokers (p=0.009). We also observed
      significant correlations for CYP2E1 promoter methylation with GSTP1 and SOD1
      promoter methylation levels (r=-.37, p<0.05 and r=-.34, p<0.05 respectively).
      CONCLUSION: These results highlight the importance of considering CYP2E1
      epigenetic modifications, as well as its interactions with other genes, as key
      factors for unraveling the sub cellular mechanisms of toxicity exerted by
      oxidative stress, which can initiate disease process in chronic, low-level
      toluene exposure. People co-exposed to toluene and tobacco smoke are in higher
      risk due to a possible CYP2E1 repression.

PMID- 25963741
TI  - Thymosin-beta4 is a determinant of drug sensitivity for Fenretinide and
      Vorinostat combination therapy in neuroblastoma.
AB  - Retinoids are an important component of neuroblastoma therapy at the stage of
      minimal residual disease, yet 40-50% of patients treated with 13-cis-retinoic
      acid (13-cis-RA) still relapse, indicating the need for more effective retinoid
      therapy. Vorinostat, or Suberoylanilide hydroxamic acid (SAHA), is a potent
      inhibitor of histone deacetylase (HDAC) classes I & II and has antitumor activity
      in vitro and in vivo. Fenretinide (4-HPR) is a synthetic retinoid which acts on
      cancer cells through both nuclear retinoid receptor and non-receptor mechanisms.
      In this study, we found that the combination of 4-HPR + SAHA exhibited potent
      cytotoxic effects on neuroblastoma cells, much more effective than 13-cis-RA +
      SAHA. The 4-HPR + SAHA combination induced caspase-dependent apoptosis through
      activation of caspase 3, reduced colony formation and cell migration in vitro,
      and tumorigenicity in vivo. The 4-HPR and SAHA combination significantly
      increased mRNA expression of thymosin-beta-4 (Tbeta4) and decreased mRNA
      expression of retinoic acid receptor alpha (RARalpha). Importantly, the up
      regulation of Tbeta4 and down-regulation of RARalpha were both necessary for the
      4-HPR + SAHA cytotoxic effect on neuroblastoma cells. Moreover, Tbeta4 knockdown
      in neuroblastoma cells increased cell migration and blocked the effect of 4-HPR +
      SAHA on cell migration and focal adhesion formation. In primary human
      neuroblastoma tumor tissues, low expression of Tbeta4 was associated with
      metastatic disease and predicted poor patient prognosis. Our findings demonstrate
      that Tbeta4 is a novel therapeutic target in neuroblastoma, and that 4-HPR + SAHA
      is a potential therapy for the disease. 

PMID- 25963743
TI  - Tissue structure and inflammatory processes shape viscoelastic properties of the
      mouse brain.
AB  - Magnetic resonance elastography (MRE) is an imaging method that reveals the
      mechanical properties of tissue, modelled as a combination of " viscosity" and "
      elasticity" . We recently showed reduced brain viscoelasticity in multiple
      sclerosis (MS) patients compared with healthy controls, and in the relapsing
      remitting disease model experimental autoimmune encephalomyelitis (EAE). However,
      the mechanisms by which these intrinsic tissue properties become altered remain
      unclear. This study investigates whether distinct regions in the mouse brain
      differ in their native viscoelastic properties, and how these properties are
      affected during chronic EAE in C57Bl/6 mice and in mice lacking the cytokine
      interferon-gamma. IFN-gamma(-/-) mice exhibit a more severe EAE phenotype, with
      amplified inflammation in the cerebellum and brain stem. Brain scans were
      performed in the sagittal plane using a 7 T animal MRI scanner, and the anterior
      (cerebral) and posterior (cerebellar) regions analyzed separately. MRE
      investigations were accompanied by contrast-enhanced MRI scans, and by
      histopathology and gene expression analysis ex vivo. Compared with the cerebrum,
      the cerebellum in healthy mice has a lower viscoelasticity, i.e. it is
      intrinsically " softer" . This was seen both in the wild-type mice and the
      IFNgamma(-/-) mice. During chronic EAE, C57Bl/6 mice did not show altered brain
      viscoelasticity. However, as expected, the IFNgamma(-/-) mice showed a more
      severe EAE phenotype, and these mice did show altered brain elasticity during the
      course of disease. The magnitude of the elasticity reduction correlated with
      F4/80 gene expression, a marker for macrophages/microglia in inflamed central
      nervous system tissue. Together these results demonstrate that MRE is sensitive
      enough to discriminate between viscoelastic properties in distinct anatomical
      structures in the mouse brain, and to confirm a further relationship between
      cellular inflammation and mechanical alterations of the brain. This study
      underscores the utility of MRE to monitor pathological tissue alterations in
      vivo.

PMID- 25963744
TI  - Determination of polyphenol and crude nutrient content and nutrient digestibility
      of dried and ensiled white and red grape pomace cultivars.
AB  - The present study aimed to determine the nutrient and energy content of fresh and
      ensiled grape pomace (GP) from different grape varieties originating from
      Germany, and to estimate the feed value of dried white, dried red and ensiled
      white GP by calculating nutrient digestibility and the content of metabolisable
      energy (ME) and net energy lactation (NEL) measured in sheep as a ruminant model.
      GP from red cultivars had higher contents of organic matter (OM), crude protein
      (CP), ether extract (EE), crude fibre (CF), total phenolic contents (TPC) and ME,
      whereas the concentrations of ash and sugar were lower than from white cultivars.
      Compared with untreated GP, ensiled GP had increased concentrations of CP (+19%),
      ether extract (EE; +23%) and CF (+12%) and a higher ME content (+7%) and markedly
      decreased concentrations of sugar (-99.6%) and TPC (-48%). The concentrations of
      dry matter, OM and ash were not different between ensiled and fresh GP. Compared
      with dried GP, ensiled GP had a higher nutrient digestibility (OM, +32%; CP,
      +43%; CF, +46%; neutral detergent fibre [NDF], +54%; acid detergent fibre [ADF],
      +69%) and higher energy values (ME, +16%; NEL, +19%). The digestibility of OM,
      CP, EE and CF and the energy content were higher for dried red than for dried
      white GP, whereas the digestibility of NDFOM and ADFOM was lower for dried red
      than dried white GP. In conclusion, the results show that both red and white GP
      are suitable dietary sources for enrichment with TPC. Furthermore, compared with
      drying ensiling of GP improves the feeding value of GP and is a good possibility
      of preserving the seasonally produced by-product of winemaking for ruminant
      feeding. 

PMID- 25963745
TI  - Assessing cost-effectiveness of HPV vaccines with decision analytic models: what
      are the distinct challenges of low- and middle-income countries? A protocol for a
      systematic review.
AB  - BACKGROUND: Cervical cancer poses a huge health burden, both to developed and
      developing nations, making prevention and control strategies necessary. However,
      the challenges of designing and implementing prevention strategies differ for low
      and middle-income countries (LMICs) as compared to countries with fully
      developed health care systems. Moreover, for many LMICs, much of the data needed
      for decision analytic modelling, such as prevalence, will most likely only be
      partly available or measured with much larger uncertainty. Lastly, imperfect
      implementation of human papillomavirus (HPV) vaccination may influence the
      effectiveness of cervical cancer prevention in unpredictable ways. This
      systematic review aims to assess how decision analytic modelling studies of HPV
      cost-effectiveness in LMICs accounted for the particular challenges faced in such
      countries. Specifically, the study will assess the following: (1) whether the
      existing literature on cost-effectiveness modelling of HPV vaccines acknowledges
      the distinct challenges of LMICs, (2) how these challenges were accommodated in
      the models, (3) whether certain parameters systemically exhibited large degrees
      of uncertainty due to lack of data and how influential were these parameters on
      model-based recommendations, and (4) whether the choice of modelling herd
      immunity influences model-based recommendations, especially when coverage of a
      HPV vaccination program is not optimal. METHODS: We will conduct a systematic
      review to identify suitable studies from MEDLINE (via PubMed), EMBASE, NHS
      Economic Evaluation Database (NHS EED), EconLit, Web of Science, and CEA
      Registry. Searches will be conducted for studies of interest published since
      2006. The searches will be supplemented by hand searching of the most relevant
      papers found in the search. Studies will be critically appraised using
      Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement
      checklist. We will undertake a descriptive, narrative, and interpretative
      synthesis of data to address the study objectives. DISCUSSION: The proposed
      systematic review will assess how the cost-effectiveness studies of HPV vaccines
      accounted for the distinct challenges of LMICs. The gaps identified will expose
      areas for additional research as well as challenges that need to be accounted for
      in future modelling studies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
      CRD42015017870.

PMID- 25963746
TI  - Additional effects of engineered stem cells expressing a therapeutic gene and
      interferon-beta in a xenograft mouse model of endometrial cancer.
AB  - Endometrial cancer is the most common gynecologic malignancy in women worldwide.
      In the present study, we evaluated the effects of neural stem cell-directed
      enzyme/prodrug therapy (NDEPT) designed to more selectively target endometrial
      cancer. For this, we employed two different types of neural stem cells (NSCs),
      HB1.F3.CD and HB1.F3.CD.IFN-beta cells. Cytosine deaminase (CD) can convert the
      non-toxic prodrug, 5-fluorocytosine (5-FC), into a toxic agent, 5-fluorouracil (5
      FU), which inhibits DNA synthesis. IFN-beta is a powerful cytotoxic cytokine that
      is released by activated immune cells or lymphocytes. In an animal model
      xenografted with endometrial Ishikawa cancer cells, the stem cells stained with
      CM-DiI were injected into nearby tumor masses and 5-FC was delivered by
      intraperitoneal injection. Co-expression of CD and IFN-beta significantly
      inhibited the growth of cancer (~50-60%) in the presence of 5-FC. Among migration
      induced factors, VEGF gene was highly expressed in endometrial cancer cells.
      Histological analysis showed that the aggressive nature of cancer was inhibited
      by 5-FC in the mice treated with the therapeutic stem cells. Furthermore, PCNA
      expression was more decreased in HB1.F3.CD.IFN-beta treated mice rather than
      HB1.F3.CD treated mice. To confirm the in vitro combined effects of 5-FU and IFN
      beta, 5-FU was treated in Ishikawa cells. 5-FU increased the IFN-beta/receptor 2
      (IFNAR2) and BXA levels, indicating that 5-FU increased sensitivity of
      endometrial cancer cells to IFN-beta, leading to apoptosis of cancer cells. Taken
      together, these results provide evidence for the efficacy of therapeutic stem
      cell-based immune therapy involving the targeted expression of CD and IFN-beta
      genes at endometrial cancer sites.

PMID- 25963747
TI  - Energetics and behavior: many paths to understanding.

PMID- 25963748
TI  - [Extreme liver resection down to the remnant monosegment level after regeneration
      induction by the ALPSS procedure].

PMID- 25963749
TI  - [Management of complications in anal and transanal tumor surgery].
AB  - Anal and transanal tumor operations are safe and are associated with a very low
      morbidity. Perianal and anal lesions as well as low rectal tumors can be excised
      by direct exposure using an anal retractor. For lesions situated in the middle or
      upper third of the rectum, special instrumentation, such as transanal endoscopic
      microsurgery (TEM) and transanal endoscopic operation (TEO) should be used to
      avoid unnecessary R1 resections. Fatal complications are extremely rare and most
      complications, such as urinary retention or temporary subfebrile temperatures,
      are minor. Suture line dehiscences are usually clinically unremarkable. Major
      complications comprise significant hemorrhage and opening of the peritoneal
      cavity. The latter must be recognized intraoperatively and can usually be managed
      by primary suturing. Infections, abscess formation, rectovaginal fistula, injury
      of the prostate or even urethra are extremely rare complications. 

PMID- 25963750
TI  - Joule heating monitoring in a microfluidic channel by observing the Brownian
      motion of an optically trapped microsphere.
AB  - Electric fields offer a variety of functionalities to Lab-on-a-Chip devices. The
      use of these fields often results in significant Joule heating, affecting the
      overall performance of the system. Precise knowledge of the temperature profile
      inside a microfluidic device is necessary to evaluate the implications of heat
      dissipation. This article demonstrates how an optically trapped microsphere can
      be used as a temperature probe to monitor Joule heating in these devices. The
      Brownian motion of the bead at room temperature is compared with the motion when
      power is dissipated in the system. This gives an estimate of the temperature
      increase at a specific location in a microfluidic channel. We demonstrate this
      method with solutions of different ionic strengths, and establish a precision of
      0.9 K and an accuracy of 15%. Furthermore, it is demonstrated that transient
      heating processes can be monitored with this technique, albeit with a limited
      time resolution. 

PMID- 25963751
TI  - Combined pressure-thermal inactivation effect on spores in lu-wei beef--a
      traditional Chinese meat product.
AB  - AIMS: This study investigated the inactivation effect and kinetics of Bacillus
      coagulans and Geobacillus stearothermophilus spores suspended in lu-wei beef by
      combining high pressure (500 and 600 MPa) and moderate heat (70 and 80  degrees C
      or 80 and 90  degrees C). METHODS AND RESULTS: During pressurization, the
      temperature of pressure-transmitting fluid was tested with a K-type thermocouple,
      and the number of surviving cells was determined by a plate count method. The
      pressure come-up time and corresponding inactivation of Bacillus coagulans and G.
      stearothermophilus spores were considered during the pressure-thermal treatment.
      For the two types of spores, the results showed a higher inactivation effect in
      phosphate buffer solution than that in lu-wei beef. Among the bacteria evaluated,
      G. stearothermophilus spores had a higher resistance than B. coagulans spores
      during the pressure-thermal processing. One linear model and two nonlinear models
      (i.e. the Weibull and log-logistic models) were fitted to the survivor data to
      obtain relevant kinetic parameters, and the performance of these models was
      compared. The results suggested that the survival curve of the spores could be
      accurately described utilizing the log-logistic model, which produced the best
      fit for all inactivation data. CONCLUSIONS: The compression heating
      characteristics of different pressure-transmitting fluids should be considered
      when using high pressure to sterilize spores, particularly while the pressure is
      increasing. Spores can be inactivated by combining high pressure and moderate
      heat. SIGNIFICANCE AND IMPACT OF THE STUDY: The study demonstrates the
      synergistic inactivation effect of moderate heat in combination with high
      pressure in real-life food. The use of mathematical models to predict the
      inactivation for spores could help the food industry further to develop optimum
      process conditions.

PMID- 25963752
TI  - Social categorization and cooperation in motor joint action: evidence for a joint
      end-state comfort.
AB  - The present study investigated to what extent group membership affects an actor's
      representation of their partner's task in cooperative joint action. Participants
      performed a joint pick-and-place task in a naturalistic, breakfast-table-like
      paradigm which allowed the demonstration of varying degrees of cooperation.
      Participants transported a wooden cup from one end of a table to the other, with
      one actor moving it to an intermediate position from where their partner
      transported it to a goal position. Hand and finger movements were recorded via 3D
      motion tracking to assess actors' cooperative behavior. Before the joint action
      task was performed, participants were categorized as belonging to the same or to
      different groups, supposedly based on an assessment of their cognitive processing
      styles. Results showed that the orientation of the actors' fingers when picking
      up the cup was affected by its required angle at the goal position. When placing
      the cup at the intermediate position, most actors adapted the rotation of the
      cup's handle to the joint action goal, thereby facilitating the partner's
      subsequent movement. Male actors demonstrated such cooperative behavior only when
      performing the task together with an ingroup partner, while female actors
      demonstrated cooperative behavior irrespective of social categorization. These
      results suggest that actors tend to represent a partner's end-state comfort and
      integrate it into their own movement planning in cooperative joint action.
      However, social factors like group membership may modulate this tendency. 

PMID- 25963753
TI  - Infants' prospective control during object manipulation in an uncertain
      environment.
AB  - This study investigates how infants use visual and sensorimotor information to
      prospectively control their actions. We gave 14-month-olds two objects of
      different weight and observed how high they were lifted, using a Qualisys Motion
      Capture System. In one condition, the two objects were visually distinct
      (different color condition) in another they were visually identical (same color
      condition). Lifting amplitudes of the first movement unit were analyzed in order
      to assess prospective control. Results demonstrate that infants lifted a light
      object higher than a heavy object, especially when vision could be used to assess
      weight (different color condition). When being confronted with two visually
      identical objects of different weight (same color condition), infants showed a
      different lifting pattern than what could be observed in the different color
      condition, expressed by a significant interaction effect between object weight
      and color condition on lifting amplitude. These results indicate that (a) visual
      information about object weight can be used to prospectively control lifting
      actions and that (b) infants are able to prospectively control their lifting
      actions even without visual information about object weight. We argue that
      infants, in the absence of reliable visual information about object weight,
      heighten their dependence on non-visual information (tactile, sensorimotor
      memory) in order to estimate weight and pre-adjust their lifting actions in a
      prospective manner. 

PMID- 25963754
TI  - Central sensitization and changes in conditioned pain modulation in people with
      chronic nonspecific low back pain: a case-control study.
AB  - Quantitative sensory testing is widely used in human research to investigate the
      state of the peripheral and central nervous system contributions in pain
      processing. It is a valuable tool to help identify central sensitization and may
      be important in the treatment of low back pain. The aim of this study was to
      evaluate changes in local and segmental hypersensitivity and endogenous pain
      inhibition in people with chronic nonspecific low back pain. Thirty patients with
      chronic low back pain and thirty healthy subjects were studied. Pressure pain
      thresholds (PPTs) were measured from the lumbar region and over the tibialis
      anterior muscle (TA). A cold pressor test was used to assess the activation of
      conditioned pain modulation (CPM), and PPTs in the lumbar region were recorded 30
      s after immersion of participant's foot in a bucket with cold water. People with
      chronic low back pain have significantly lower PPT than controls at both the
      lumbar region [89.5 kPa (mean difference) 95 % CI 40.9-131.1 kPa] and TA [59.45
      kPa (mean difference) 95 % CI 13.49-105.42 kPa]. During CPM, people with chronic
      low back pain have significantly lower PPT than controls in lumbar region [118.6
      kPa (mean difference) 95 % CI 77.9-159.2 kPa]. Women had significantly lower PPTs
      than men in both lumbar region [101.7 kPa (mean difference) 95 % CI 37.9-165.7
      kPa] and over the TA [189.7 kPa (mean difference) 95 % CI 14.2-145.2 kPa]. There
      was no significant difference in PPTs in men between healthy controls and those
      with low back pain, suggesting the significant differences are mediated primarily
      by difference between women. 

PMID- 25963755
TI  - Effects of transcranial direct current stimulation (tDCS) on multiscale
      complexity of dual-task postural control in older adults.
AB  - Transcranial direct current stimulation (tDCS) targeting the prefrontal cortex
      reduces the size and speed of standing postural sway in younger adults,
      particularly when performing a cognitive dual task. Here, we hypothesized that
      tDCS would alter the complex dynamics of postural sway as quantified by
      multiscale entropy (MSE). Twenty healthy older adults completed two study visits.
      Center-of-pressure (COP) fluctuations were recorded during single-task (i.e.,
      quiet standing) and dual-task (i.e., standing while performing serial
      subtractions) conditions, both before and after a 20-min session of real or sham
      tDCS. MSE was used to estimate COP complexity within each condition. The
      percentage change in complexity from single- to dual-task conditions (i.e., dual
      task cost) was also calculated. Before tDCS, COP complexity was lower (p = 0.04)
      in the dual-task condition as compared to the single-task condition. Neither real
      nor sham tDCS altered complexity in the single-task condition. As compared to
      sham tDCS, real tDCS increased complexity in the dual-task condition (p = 0.02)
      and induced a trend toward improved serial subtraction performance (p = 0.09).
      Moreover, those subjects with lower dual-task COP complexity at baseline
      exhibited greater percentage increases in complexity following real tDCS (R = 
      0.39, p = 0.05). Real tDCS also reduced the dual-task cost to complexity (p =
      0.02), while sham stimulation had no effect. A single session of tDCS targeting
      the prefrontal cortex increased standing postural sway complexity with concurrent
      non-postural cognitive task. This form of noninvasive brain stimulation may be a
      safe strategy to acutely improve postural control by enhancing the system's
      capacity to adapt to stressors. 

PMID- 25963756
TI  - Effect of Medications on Risk of Cancer in Patients With Inflammatory Bowel
      Diseases: A Population-Based Cohort Study from Olmsted County, Minnesota.
AB  - OBJECTIVES: To estimate the overall risk of cancer in a population-based cohort
      of patients with inflammatory bowel disease (IBD) and how IBD-related medications
      modify this risk. METHODS: We identified all incident cancers (excluding
      nonmelanoma skin cancer) after IBD diagnosis in a cohort of 839 patients
      diagnosed as having IBD from January 1, 1940, through December 31, 2004, in
      Olmsted County, Minnesota, and followed up for a median 18 years through December
      31, 2011 (122 patients taking biologic agents at last follow-up). We calculated
      standardized incidence ratios (SIRs) with 95% CIs of all cancers and compared
      cancer risk in patients treated with immunomodulators (IMMs) and biologics with
      that of patients not exposed to these medications, using an incidence rate ratio
      (IRR). RESULTS: One hundred nine patients developed 135 cancers. The 10-year
      cumulative probability of cancer was 3.8%. Patients with Crohn disease (SIR, 1.6;
      95% CI, 1.2-2.1) but not ulcerative colitis (SIR, 1.1; 95% CI, 0.8-1.4) had an
      increased overall risk of cancer compared with the general population. Patients
      treated with IMMs (relative to IMM-naive patients) had an increased risk of
      melanoma (IRR, 5.3; 95% CI, 1.1-24.8) (and a numerically higher risk of
      hematologic malignant tumors [IRR, 4.2; 95% CI, 0.9-19.2]), although this risk
      returned to baseline on discontinuation of IMM treatment. Patients treated with
      biologics (relative to biologic-naive patients) had a numerically higher risk of
      hematologic malignant tumors (IRR, 5.3; 95% CI, 0.7-40.5). There was no
      significant increase in the risk of gastrointestinal malignancies in patients
      with IBD compared with the general population. CONCLUSIONS: We observed an
      increased risk of melanoma in IMM-treated patients with IBD, and this risk
      returned to baseline after discontinued use of the medications.

PMID- 25963757
TI  - Lateral medullary infarction in a patient with central nervous system lupus.

PMID- 25963758
TI  - Effectiveness of intra-articular injections of sodium bicarbonate and calcium
      gluconate in the treatment of osteoarthritis of the knee: a randomized double
      blind clinical trial.
AB  - BACKGROUND: A novel therapeutic management of osteoarthritis (OA) of the knee was
      assessed. The study aimed to evaluate the effect of monthly sodium bicarbonate
      with a single (SBCG1) or double dose (SBCG2) of calcium gluconate injections on
      OA of the knee; as well as the efficacy and safety of both SBCG interventions in
      the long term. METHODS: A double-blind parallel-group clinical trial with 74 knee
      OA patients was performed during 12 months, both SBCG interventions were followed
      up for another 6mo after intervention. The outcome variables were the Western
      Ontario-McMaster University Osteoarthritis Index (WOMAC), the Lequesne's
      functional index and joint-space width changes from serial radiographs. RESULTS:
      After 12 months, group SBCG1 decreased -14.8 (95% CI:-14.2, -17.0) and group
      SBCG2 decreased -14.6 (-16.9, -12.4) in the global WOMAC score, the mean changes
      represent 80% and 82% lessened pain, respectively. In the Lequesne Functional
      Index scale, SBCG1 decreased -11.9 (-10.4, -14.2) and SBCG2 decreased -11.9 (
      13.8, -10.0), representing 66 and 69% of improvement. Both mean scores were
      maintained after intervention discontinued. SBCG2 improved the knees' joint space
      width more than SBCG1 at 3 and 18 months. Both SBCG interventions were well
      tolerated after 12 months of treatment CONCLUSION: A solution of sodium
      bicarbonate and calcium gluconate is effective on reducing the symptoms
      associated with OA. Its beneficial effect is maintained for one year of
      continuous monthly administration and at least for 6 months after the
      administration is discontinued. When the dose of calcium gluconate is increased,
      it prevents further narrowing of joint-space. TRIAL REGISTRATION:
      Clinicaltrials.gov NCT00977444 September 11, 2009.

PMID- 25963759
TI  - Host-feeding preference of Phlebotomus orientalis (Diptera: Psychodidae) in an
      endemic focus of visceral leishmaniasis in northern Ethiopia.
AB  - BACKGROUND: Blood-feeding behavior studies are important for estimating the
      efficiency of pathogen transmission and assessing the relative human disease
      risk. However, in Ethiopia and other parts of East Africa there are large
      remaining gaps in identifying the feeding habits of Phlebotomus orientalis, the
      vector of Leishmania donovani. The aim of the study was to determine the blood
      feeding patterns of P. orientalis in Tahtay Adiyabo district, northern Ethiopia.
      METHODS: For bloodmeal analysis, sandflies were collected from three different
      villages of Tahtay Adiyabo district using CDC light traps, sticky traps, and
      pyrethrum spray catches. Bloodmeal of engorged female sandflies was identified
      using cytochrome (cyt) b-PCR and reverse-line blotting (RLB) and enzyme linked
      immunosorbent assay (ELISA) assays. RESULTS: Most (637/641) of the females
      analyzed were P. orientalis. Successful identification of the host from
      bloodmeals was achieved in 83.03 and 92.1% using cyt b PCR-RLB and ELISA,
      respectively. Bloodmeal analysis of P. orientalis females revealed that they have
      a range of hosts with predominant preference to bovines followed by donkey,
      human, goat, sheep, dog, and camel. CONCLUSION: Results obtained from bloodmeal
      analyses demonstrate that the feeding preference of P. orientalis is mainly
      zoophilic, which could vary depending on the availability of hosts.

PMID- 25963760
TI  - Framework tool for a rapid cumulative effects assessment: case of a prominent
      wetland in Myanmar.
AB  - The wetland of focus, Inle Lake, located in central Myanmar, is well known for
      its unique biodiversity and culture, as well as for ingenious floating garden
      agriculture. During the last decades, the lake area has seen extensive
      degradation in terms of water quality, erosion, deforestation, and biodiversity
      concomitant with a major shift to unsustainable land use. The study was
      conducted, with an emphasis on water quality, to analyze environmental impacts
      (effects) changing the ecosystem and to comprehensively evaluate the
      environmental state of the ecosystem through an innovative Rapid Cumulative
      Effects Assessment framework tool. The assessment started with a framework
      forming Participatory Rural Appraisal (PRA), which quantified and prioritized
      impacts over space and time. Critically important impacts were assessed for
      "intra-inter interactions" using the loop analysis simulation. Water samples were
      analyzed while geographic information system (GIS) and remote sensing were used
      to identify water pollution hotspots. It was concluded that out of a plethora of
      impacts, pollution from municipal sources, sedimentation, and effects exerted by
      floating gardens had the most detrimental impacts, which cumulatively affected
      the entire ecosystem. The framework tool was designed in a broad sense with a
      reference to highly needed assessments of poorly studied wetlands where
      degradation is evident, but scarcely quantified, and where long-term field
      studies are fraught with security issues and resource unavailability (post
      conflict, poor and remote regions, e.g., Afghanistan, Laos, Sudan, etc.). 

PMID- 25963761
TI  - Fractionation of heavy metals in bottom sediments in Chahnimeh 1, Zabol, Iran.
AB  - In the present study, 180 sediment samples were collected from the Chahnimeh 1
      reservoir to investigate the concentration of metal and sequential extraction.
      Five geochemical phases (exchangeable fraction, carbonate fraction, Fe/Mn oxide
      fraction, organic fraction and residual fraction) for the determination of the
      speciation of heavy metals (Zn, Fe, Cd, Pb, Mn, Ni) as proposed by Tessier was
      applied to sediments collected from Chahnimeh 1. Results were obtained for nickel
      and cadmium, as over 40 % of metal was present in the exchangeable phase and
      bound to carbonate. According to the risk assessment code (RAC), sediments that
      have 31 to 50 % carbonate and exchangeable fraction are high risk. Similar
      results were obtained for zinc and lead. The major fraction of the two metals (63
      % of the total concentration for lead and 85 % of the total concentration for
      zinc) occurred in the residual phase and fraction-bound hydrous Fe-Mn oxides. The
      risk assessment showed moderate risk for lead and no risk for zinc. This
      indicates that the Igeo and IPOLL used in the present investigation showed no
      pollution to moderate pollution in terms of metals in sediments.

PMID- 25963762
TI  - Riverine tot-P loading and seawater concentrations in the Baltic Sea during the
      1970s to 2000-transfer function modelling based on the total runoff.
AB  - The signal of climate through the North Atlantic Oscillation (NAO) extends to
      westerly weather and to the Baltic Sea river runoff (BSRR) and further to the
      salinity and the marine fauna in the Baltic Sea. Our working hypothesis was that
      increased BSRR should also lead to increasing nutrient concentrations in the
      seawater. In rivers, transfer function (TF) models of the loading were
      constructed by time series of BSRR and tot-P concentrations. Based on the loading
      time series, we modelled, to our knowledge, first time, seawater tot-P
      concentrations in both the Northern Baltic Proper and in the Gulf of Bothnia,
      both on the surface (0-20 m) and deeper (21-70 m) waters. Our results further
      suggest a unifying mechanism by the BSRR that could explain most prominent
      ecological changes observed in the Baltic Sea during and after the 1970s. Such
      changes are eutrophication (as in this paper) and decreasing salinity and growth
      and reproduction of marine fauna, all of which have been separately described as
      due to different causes. BSRR is crucial when possible future developments of the
      Baltic Sea environment are considered because a general opinion exists that the
      rainfall (and the BSRR) is expected to increase in pace with proceeding climate
      change.

PMID- 25963763
TI  - Densities and antimicrobial resistance of Escherichia coli isolated from marine
      waters and beach sands.
AB  - Bacterial resistance is a rising problem all over the world. Many studies have
      showed that beach sands can contain higher concentration of microorganisms and
      represent a risk to public health. This paper aims to evaluate the densities and
      resistance to antimicrobials of Escherichia coli strains, isolated from seawater
      and samples. The hypothesis is that microorganisms show higher densities in
      contaminated beach sands and more antimicrobial resistance than the water column.
      Density, distribution, and antimicrobial resistance of bacteria E. coli were
      evaluate in seawater and sands from two recreational beaches with different
      levels of pollution. At the beach with higher degree of pollution (Gonzaguinha),
      water samples presented the highest densities of E. coli; however, higher
      frequency of resistant strains was observe in wet sand (71.9 %). Resistance to a
      larger number of antimicrobial groups was observe in water (betalactamics,
      aminoglycosides, macrolides, rifampicins, and tetracyclines) and sand
      (betagalactamics and aminoglycosids). In water samples, highest frequencies of
      resistance were obtain against ampicilin (22.5 %), streptomycin (15.0 %), and
      rifampicin (15.0 %), while in sand, the highest frequencies were observe in
      relation to ampicilin (36.25 %) and streptomycin (23.52 %). At the less polluted
      beach, Ilha Porchat, highest densities of E. coli and higher frequency of
      resistance were obtain in wet and dry sand (53.7 and 53.8 %, respectively)
      compared to water (50 %). Antimicrobial resistance in strains isolated from water
      and sand only occurred against betalactamics (ampicilin and amoxicilin plus
      clavulanic acid). The frequency and variability of bacterial resistance to
      antimicrobials in marine recreational waters and sands were related to the degree
      of fecal contamination in this environment. These results show that water and
      sands from beaches with a high index of fecal contamination of human origin may
      be potential sources of contamination by pathogens and contribute to the
      dissemination of bacterial resistance.

PMID- 25963764
TI  - Environmental risk of heavy metal pollution and contamination sources using
      multivariate analysis in the soils of Varanasi environs, India.
AB  - This study assessed soil pollution in the Varanasi environs of Uttar Pradesh in
      India. Assessing the concentration of potentially harmful heavy metals in the
      soils is imperative in order to evaluate the potential risks to human. To
      identify the concentration and sources of heavy metals and assess the soil
      environmental quality, 23 samples were collected from different locations
      covering dumping, road and agricultural area. The average concentrations of the
      heavy metals were all below the permissible limits according to soil quality
      guidelines except Cu (copper) and Pb (lead) in dumping and road soils. Soil heavy
      metal contamination was assessed on the basis of geoaccumulation index (Igeo),
      pollution index (PI) and integrated pollution index (IPI). The IPI of the metals
      ranged from 0.59 to 9.94, with the highest IPI observed in the dumping and road
      soils. A very significant correlation was found between Pb and Cu. The result of
      principal component analysis suggested that PC1 was mainly affected by the use of
      agrochemicals, PC2 was affected by vehicular emission and PC3 was affected by
      dumping waste. Meanwhile, PC4 was mainly controlled by parent material along with
      anthropogenic activities. Appropriate measures should be taken to minimize the
      heavy metal levels in soils and thus protect human health. 

PMID- 25963765
TI  - Dissipation, residues, and safety evaluation of trifloxystrobin and tebuconazole
      on ginseng and soil.
AB  - Supervised field trials at two locations in 2012 and 2013 were conducted to
      evaluate the dissipation, terminal residues, and safety evaluation of Nativo 75
      water dispersible granule (WG) (25 % trifloxystrobin + 50 % tebuconazole) on
      ginseng and soil following foliar application at a recommended dose 150 (50 +
      100) and 1.5 times of the recommended dosage 225 (75 + 150) g a.i. ha(-1). The
      average recoveries of trifloxystrobin and tebuconazole at three spiking levels in
      ginseng root, stem, and leaf and in soil were in the ranges of 81.0-96.8 % and
      80.2-97.5 % with relative standard deviations (RSDs) of 4.92-13.13 % and 4.67
      8.35 %, respectively. The half-lives of trifloxystrobin and tebuconazole were
      5.92-9.76 days and 4.59-7.53 days, respectively. The terminal residues were all
      below the maximum residue limits (MRLs) of EU, USA, Canada, Japan, and South
      Korea. The food safety was evaluated by comparing the estimated daily intake
      (IEDI) with its acceptable daily intake (ADI). IEDI values calculated from
      residue data were found to be far less than the ADI on ginseng. Therefore, it
      would be unlikely to cause health problems induced by Nativo 75 WG use on ginseng
      at a dosage of 150-225 g a.i. ha(-1).

PMID- 25963766
TI  - Frailty Plays a Key Role after Cardiac Surgery.

PMID- 25963767
TI  - Heritability of dietary traits that contribute to nephrolithiasis in a cohort of
      adult sibships.
AB  - BACKGROUND: Kidney stones and their risk factors aggregate in families, yet few
      studies have estimated the heritability of known risk factors. OBJECTIVE:
      Estimate the heritability of dietary risk factors for kidney stones. METHODS:
      Dietary intakes were assessed using the Viocare Food Frequency Questionnaire in
      sibships enrolled in the Rochester, MN cohort of the Genetic Epidemiology Network
      of Arteriopathy. Measures of urinary supersaturation were determined using 24 h
      urine samples. Heritabilities and genetic correlations were estimated using
      variance components methods. RESULTS: Samples were available from 620 individuals
      (262 men, 358 women, mean (SD) age 65 (9) years). Dietary intakes of protein,
      sucrose, and calcium had strong evidence for heritability (p < 0.01) after
      adjustment for age, sex, height and weight. Among the significantly heritable
      dietary intakes (p < 0.05), genetic factors explained 22-50 % of the inter
      individual variation. Significant genetic correlations were observed among
      dietary protein, dietary sucrose, and dietary calcium intakes (p < 0.001).
      CONCLUSIONS: Evidence from this relatively large cohort suggests a strong
      heritable component to dietary intakes of protein, sucrose and calcium that
      contributes to nephrolithiasis risk. Further efforts to understand the interplay
      of genetic and environmental risk factors in kidney stone pathogenesis are
      warranted.

PMID- 25963768
TI  - Investigation of molecular mechanisms and regulatory pathways of pro-angiogenic
      nanorods.
AB  - Angiogenesis, a process involving the growth of new blood vessels from the pre
      existing vasculature, plays a crucial role in various pathophysiological
      conditions. We have previously demonstrated that europium hydroxide
      [Eu(III)(OH)3] nanorods (EHNs) exhibit pro-angiogenic properties through the
      generation of reactive oxygen species (ROS) and mitogen activated protein kinase
      (MAPK) activation. Considering the enormous implication of angiogenesis in
      cardiovascular diseases (CVDs) and cancer, it is essential to understand in-depth
      molecular mechanisms and signaling pathways in order to develop the most
      efficient and effective alternative treatment strategy for CVDs. However, the
      exact underlying mechanism and cascade signaling pathways behind the pro
      angiogenic properties exhibited by EHNs still remain unclear. Herein, we report
      for the first time that the hydrogen peroxide (H2O2), a redox signaling molecule,
      generated by these EHNs activates the endothelial nitric oxide synthase (eNOS)
      that promotes the nitric oxide (NO) production in a PI3K (phosphoinositide 3
      kinase)/Akt dependent manner, eventually triggering angiogenesis. We intensely
      believe that the investigation and understanding of the in-depth molecular
      mechanism and signaling pathways of EHNs induced angiogenesis will help us in
      developing an effective alternative treatment strategy for cardiovascular related
      and ischemic diseases where angiogenesis plays an important role. 

PMID- 25963769
TI  - Spine-Hip Thickness Difference Measured by Dual-Energy X-ray Absorptiometry Is
      Associated With Diabetes Mellitus in Women and Men.
AB  - Abdominal adiposity is strongly associated with a range of chronic metabolic and
      cardiovascular morbidities, including type 2 diabetes mellitus, and may play a
      causal role in their development. Dual-energy X-ray absorptiometry (DXA) of the
      lumbar spine and hip is widely used for assessment of osteoporosis and also
      measures tissue thickness. We hypothesized that the difference in spine and hip
      tissue thickness from regional DXA scans might provide an index of relative
      abdominal adiposity and serve as a risk factor for the presence of diabetes. We
      identified 31,648 women and 2960 men aged >=50 yr who underwent spine and hip DXA
      scans and analyzed their baseline characteristics, including presence of
      previously diagnosed diabetes in 2929 women and 460 men. Women had significantly
      lower mean spine-hip thickness differences than men (3.3 +/- 1.4 cm vs 5.4 +/-
      1.7 cm; p < 0.001), which persisted after adjustment for sex-specific differences
      in the effects of age and body mass index (BMI). Women and men with diabetes had
      significantly higher mean spine-hip thickness differences before and after
      adjustment for age and BMI. Logistic regression showed that greater spine-hip
      thickness difference was significantly associated with higher likelihood of
      diabetes even after adjustment for age and BMI, and this effect was stronger
      among women (odds ratios per standard deviation 1.88 [95% confidence interval:
      1.86-1.98]; p < 0.001) than among men (1.10 [1.03-1.18]; p = 0.007). We conclude
      that spine-hip thickness difference measured from regional DXA scans warrants
      further study as a risk factor for developing diabetes.

PMID- 25963770
TI  - Using Interactive Web-Based Screening, Brief Intervention and Referral to
      Treatment in an Urban, Safety-Net HIV Clinic.
AB  - Substance use among people living with HIV is high, and screening, brief
      intervention, and referral to treatment (SBIRT) is an evidence-based approach to
      addressing the issue. We examined whether patients would participate in a
      technology-based SBIRT program in an urban HIV clinic. An SBIRT intervention was
      programmed into the clinic's web-based patient portal linked to their personal
      health record. We examined: demographic, health, HIV, and substance use
      characteristics of participants who completed the web-based intervention compared
      to those who did not. Fewer than half of the 96 participants assigned to the web
      based SBIRT completed it (n = 39; 41 %). Participants who completed the web-based
      intervention had significantly higher amphetamine SSIS scores than those who did
      not complete the intervention. Participants whose substance use is more harmful
      may be more motivated to seek help from a variety of sources. In addition, it is
      important that technology-based approaches to behavioral interventions in clinics
      take into consideration feasibility, client knowledge, and comfort using
      technology.

PMID- 25963771
TI  - Using Capture-Recapture Methods to Estimate the Population of People Who Inject
      Drugs in Washington, DC.
AB  - No current estimates exist for the size of the population of people who inject
      drugs (PWID) in the District of Columbia (DC). The WHO/UNAIDS Guidelines on
      Estimating the Size of Populations Most at Risk to HIV was used as the
      methodological framework to estimate the DC PWID population. The capture phase
      recruited harm reduction agency clients; the recapture phase recruited community
      based PWID. The 951 participants were predominantly Black (83.9 %), male (69.8
      %), and 40+ years of age (68.2 %). Approximately 50.3 % reported injecting drugs
      in the past 30 days. We estimate approximately 8829 (95 % CI 4899 and 12,759)
      PWID in DC. When adjusted for possible missed sub-populations of PWID, the
      estimate increases to 12,000; thus, the original estimate of approximately 9000
      should be viewed in the context of the 95 % confidence interval. These evidence
      based estimations should be used to determine program delivery needs and resource
      allocation for PWID in Washington, DC.

PMID- 25963772
TI  - Explaining the Efficacy of Pre-exposure Prophylaxis (PrEP) for HIV Prevention: A
      Qualitative Study of Message Framing and Messaging Preferences Among US Men Who
      have Sex with Men.
AB  - We investigated message comprehension and message framing preferences for
      communicating about PrEP efficacy with US MSM. We conducted eight focus groups (n
      = 38) and n = 56 individual interviews with MSM in Providence, RI. Facilitators
      probed comprehension, credibility, and acceptability of efficacy messages,
      including percentages, non-numerical paraphrases, efficacy ranges versus point
      estimates, and success- versus failure-framed messages. Our findings indicated a
      range of comprehension and operational understandings of efficacy messages.
      Participants tended to prefer percentage-based and success-framed messages,
      although preferences varied for communicating about efficacy using a single
      percentage versus a range. Participants reported uncertainty about how to
      interpret numerical estimates, and many questioned whether trial results would
      predict personal effectiveness. These results suggest that providers and
      researchers implementing PrEP may face challenges in communicating with users
      about efficacy. Efforts to educate MSM about PrEP should incorporate percentage
      based information, and message framing decisions may influence message
      credibility and overall PrEP acceptability.

PMID- 25963773
TI  - Drug Familiarization and Therapeutic Misconception Via Direct-to-Consumer
      Information.
AB  - Promotion of prescription drugs may appear to be severely limited in some
      jurisdictions due to restrictions on direct-to-consumer advertising (DTCA).
      However, in most jurisdictions, strategies exist to raise consumer awareness
      about prescription drugs, notably through the deployment of direct-to-consumer
      information (DTCI) campaigns that encourage patients to seek help for particular
      medical conditions. In Canada, DTCI is presented by industry and regulated by
      Health Canada as being purely informational activities, but their design and
      integration in broader promotional campaigns raise very similar ethical concerns
      as those associated with DTCA. Specifically, DTCI can be an effective means of
      familiarizing the public with the scope and benefits of a particular prescription
      drug and so, like DTCA, can promote increased patient-consumer demand and thus a
      problematic rise in the prescribing and use of medications that may be neither
      the most appropriate nor the most cost-effective. Yet, with DTCI the industry is
      playing within the existing rules and regulations set by health regulators. To
      respond appropriately to this regulatory incoherence, we argue that DTCI should
      be regulated as a type of direct-to-consumer indirect advertising. Even if the
      case and specific regulations presented here are Canadian, the implications
      extend to every country that has a partial or total prohibition on DTCA. 

PMID- 25963774
TI  - MicroRNA-122 associates with serum apolipoprotein B but not liver fibrosis
      markers in CHC genotype 1 infection.
AB  - miR-122 is the predominant liver miRNA that regulates hepatic lipid metabolism
      and inflammation. Hepatitis C virus (HCV) modulates host intracellular lipid
      metabolism. HCV stability and propagation also depend on an interaction between
      virus and miR-122. Our aims were to examine the associations between miR-122,
      apolipoproteins, and serum makers of fibrosis in chronic hepatitis C (CHC)
      patients. We evaluated baseline sera from 36 CHC genotype 1 patients who
      completed the Phase IIa study of miravirsen (LNA oligonucleotide targeting miR
      122). Samples were assessed for liver transaminases, IL 28B genotype, IP-10, and
      lipid profiles. The noninvasive markers of liver fibrosis, APRI, and FIB-4, were
      calculated using standard formulae. miR-122 levels were measured using RT-PCR and
      expressed as fold-change compared to normal healthy controls. CHC patients were
      mostly male (61%) with mean age 47.5 +/- 11.6 years. Patients with higher ApoB
      (ApoB/ULN >= 0.5) has significantly lower miR-122 levels in compared to patients
      with lower ApoB (ApoB/ULN < 0.5). (8.28 +/- 6.23 vs. 16.28 +/- 13.71; P = 0.02).
      There were no similar associations between miR-122 and ApoA-1 or between HCV RNA
      and lipoproteins. There were no differences in miR-122 levels between patients
      with different stages of fibrosis determined by APRI or FIB-4. Patients with
      lower ApoB had higher serum miR-122 levels. However, we cannot identify
      significant association between miR-122, ApoA-1, or fibrosis markers in this
      small cohort of CHC genotype 1 patients. The mechanism of HCV dyslipidemia is
      complex and could partly relate to the effect of miR-122 on lipid metabolism
      which requires further evaluation in a larger study.

PMID- 25963776
TI  - Three-phase succession of autochthonous lactic acid bacteria to reach a stable
      ecosystem within 7 days of natural bamboo shoot fermentation as revealed by
      different molecular approaches.
AB  - Microbial community structure and population dynamics during spontaneous bamboo
      shoot fermentation for production of 'soidon' (indigenous fermented food) in
      North-east India were studied using cultivation-dependent and cultivation
      independent molecular approaches. Cultivation-dependent analyses (PCR-amplified
      ribosomal DNA restriction analysis and rRNA gene sequencing) and cultivation
      independent analyses (PCR-DGGE, qPCR and Illumina amplicon sequencing) were
      conducted on the time series samples collected from three independent indigenous
      soidon fermentation batches. The current findings revealed three-phase succession
      of autochthonous lactic acid bacteria to attain a stable ecosystem within 7 days
      natural fermentation of bamboo shoots. Weissella spp. (Weissella cibaria,
      uncultured Weissella ghanensis) and Lactococcus lactis subsp. cremoris
      predominated the early phase (1-2 days) which was joined by Leuconostoc citreum
      during the mid-phase (3 days), while Lactobacillus brevis and Lactobacillus
      plantarum emerged and became dominant in the late phase (5-7 days) with
      concurrent disappearance of W. cibaria and L. lactis subsp. cremoris. Lactococcus
      lactis subsp. lactis and uncultured Lactobacillus acetotolerans were
      predominantly present throughout the fermentation with no visible dynamics. The
      above identified dominant bacterial species along with their dynamics can be
      effectively utilized for designing a starter culture for industrialization of
      soidon production. Our results showed that a more realistic view on the microbial
      ecology of soidon fermentation could be obtained by cultivation-dependent studies
      complemented with cultivation-independent molecular approaches. Moreover, the
      critical issues to be considered for reducing methodological biases while
      studying the microbial ecology of traditional food fermentation were also
      highlighted with this soidon fermentation model. 

PMID- 25963775
TI  - Self-Report After Randomly Assigned Supervision Does not Predict Ability to
      Practice Motivational Interviewing.
AB  - The objective of this study was to investigate the relation between self-report
      and objective assessment of motivational interviewing (MI) skills following
      training and supervision. After an MI workshop, 96 clinicians from 26 community
      programs (age 21-68, 65% female, 40.8% Black, 29.6% Caucasian, 24.5% Hispanic,
      2.0% Asian, 3.1% other) were randomized to supervision (tele-conferencing or tape
      based), or workshop only. At four time points, trainees completed a self-report
      of MI skill, using items from the MI understanding questionnaire (MIU), and were
      objectively assessed by raters using the Motivational Interviewing Treatment
      Integrity (MITI) system. Correlations were calculated between MIU and MITI
      scores. A generalized linear mixed model was tested on MIU scores, with MITI
      scores, supervision condition and time as independent variables. MIU scores
      increased from pre-workshop (mean = 4.74, SD = 1.79) to post-workshop (mean =
      6.31, SD = 1.03) (t = 8.69, p < .0001). With supervision, scores continued to
      increase, from post-workshop to week 8 (mean = 7.07, SD = 0.91, t = 5.60, p <
      .0001) and from week 8 to week 20 (mean = 7.28, SD = 0.94, t = 2.43, p = .02).
      However, MIU scores did not significantly correlate with MITI scores, with or
      without supervision. Self-reported ability increased with supervision, but self
      report was not an indicator of objectively measured skill. This suggests that
      training does not increase correspondence between self-report and objective
      assessment, so community treatment programs should not rely on clinician self
      report to assess the need for ongoing training and supervision and it may be
      necessary to train clinicians to accurately assess their own skill.

PMID- 25963778
TI  - [Temporary use of centrifugal pump for pump thrombosis in patients with
      paracorporeal ventricular assist device].
AB  - Nipro paracorporeal ventricular assist device( VAD) is often associated with pump
      thrombosis which causes severe complications such as brain infarction, often
      requiring pump change. However, Nipro VAD pump is an expensive device and it is
      difficult to change pumps frequently at a short interval. We have temporarily
      used Rotaflow centrifugal pump for recurrent pump thrombosis in patients with
      Nipro VADs. From January 2012 through December 2013, 19 patients underwent Nipro
      VADs implantation at our institution, and 9 of them underwent pump change from
      Nipro pumps to Rotaflow centrifugal pumps. A total of 25 Rotaflow centrifugal
      pumps were used in these 9 patients, with the total circulatory support duration
      of 526 days. The median support period was 15 days (range;2-128 days). There were
      2 cerebrovascular accidents and 1 Rotaflow pump circuit thrombosis during this
      period. Change from Rotaflow to Nipro VAD pump resulted in decrease in hematocrit
      by about 3 point. There was no difference in liver or renal function between
      before and after the pump change. Our results suggest that temporary use of
      Rotaflow centrifugal pump for recurrent pump thrombosis in patients with Nipro
      VADs may be a promising alternative. 

PMID- 25963777
TI  - Case report: low-titre anti-Yo reactivity in a female patient with psychotic
      syndrome and frontoparieto-cerebellar atrophy.
AB  - BACKGROUND: Autoimmune and inflammatory mechanisms in psychotic disorders have
      attracted increasing scientific attention in recent years. In this regard, we
      performed routine cerebrospinal fluid (CSF) basic diagnostics and CSF/serum
      analyses for antibodies directed against neuronal intracellular and surface
      antigens in psychotic patients. In this context, the patient presented in this
      paper was diagnosed. CASE PRESENTATION: We present the case of a 20-year-old
      female patient with a first episode of a drug-induced psychotic syndrome but
      without neurological deficits. Further investigations showed a reproducible low
      titre positive anti-Yo reactivity in the CSF and serum with two independent
      immunoblot assays. Magnetic resonance imaging showed frontoparietal and
      cerebellar atrophy. On [(18)F]fluorodeoxyglucose positron emission tomography, a
      mild cerebellar hypometabolism was found. No underlying tumor was detected.
      CONCLUSION: Despite the presence of anti-Yo reactivity, the diagnostic criteria
      for a paraneoplastic neurological syndrome were not fulfilled. Previously
      published data indicate the possible association between low-titer antibodies
      against intracellular localized, onconeural antigens, and psychotic disorders.
      Large prospective studies that investigate the prevalence and clinical
      significance of antibodies against intracellular onconeural antigens in
      psychiatry are needed.

PMID- 25963779
TI  - [Lung Cancer Treated with Wedge Resection of the Lower Lobe of the Left Lung with
      the Assistance of Extracorporeal Membrane Oxygenation(ECMO) after Right
      Pneumonectomy].
AB  - A 59-year-old male was admitted to our hospital with an abnormal shadow on a
      chest X-ray. Right pneumonectomy and lymph node dissection (ND2a) were performed.
      A pathological examination revealed adenocarcinoma( pT3N2M0). Fourteen years
      later, chest computed tomography(CT) showed a tumor shadow in the lower lobe of
      the left lung. His pulmonary function was sufficient to allow a 2nd operation. He
      underwent wedge resection of the lower lobe of the left lung with the assistance
      of extra corporeal membrane oxygenation (ECMO). His postoperative course was
      uneventful. A pathological examination revealed large cell neuroendocrine
      carcinoma, which was 18 mm in diameter. His performance status declined slightly,
      but he had no problems associated with the activities of daily life. The patient
      is currently alive 6 months after the 2nd operation without any sign of
      recurrence. ECMO is a useful technique for thoracic surgery after pneumonectomy. 

PMID- 25963780
TI  - [Port site recurrence after thoracoscopic resection of the pulmonary metastasis
      of sigmoid colon cancer].
AB  - A 71-year-old female underwent thoracoscopic resection for pulmonary metastasis
      from sigmoid colon cancer in March 2012. After 7 months, postoperative computed
      tomography (CT) showed a chest tumor around the left 6th rib. At the same time,
      she complained of left chest pain. These findings were initially considered as
      posttreatment changes. But the lesion of the chest wall enlarged and the pain
      worsened. We made a diagnosis of chest wall recurrence and performed a surgery in
      June 2013. The pathological diagnosis was chest wall metastasis from colon
      cancer. A port site recurrence on the chest wall was strongly suggested because
      it was extremely close to the port site of thoracoscopic resection. This patient
      is free from recurrence 16 months after surgery. 

PMID- 25963781
TI  - [Right branch pulmonary artery stenosis with supravalvar aortic stenosis as a
      complication of Lecompte maneuver for tetralogy of Fallot associated with absent
      pulmonary valve].
AB  - The patient was diagnosed with tetralogy of Fallot associated with absent
      pulmonary valve syndrome and a low birth weight of 1,912 g. He suffered from
      respiratory distress on day 14 and received non-invasive positive pressure
      ventilation. At 5 months of age and 4.1 kg, he underwent intracardiac repair
      including right ventricular outflow repair with a monocusp patch, patch closure
      of the ventricular septum defect and right pulmonary transposition to the
      anterior of the ascending aorta following the Lecompte maneuver for airway
      decompression. He was subsequently discharged to home and exhibited an uneventful
      clinical course with non-invasive positive pressure ventilation for 5 months
      postoperatively. However, right pulmonary artery and supra-aortic stenosis was
      noted 2 years after the operation. Computed tomography (CT) and angiography
      showed ascending aorta strangulation by the right pulmonary artery with right
      ventricular outflow regurgitation. Right pulmonary artery reconstruction using
      polytetrafluoroethylene graft interposition and repeat right ventricular outflow
      repair with bicuspid hand-sewn valves was therefore performed;the postoperative
      course was uneventful. Pre- and post-operative management using non-invasive
      positive pressure ventilation and airway decompression with pulmonary artery
      translocation is a useful strategy in patients exhibiting symptomatic tetralogy
      of Fallot associated with absent pulmonary valve syndrome in the neonatal period.

PMID- 25963782
TI  - [Left Ventricular Rupture during Both Mitral and Aortic Valve Replacements].
AB  - A 73-year-old woman on hemodialysis was transferred to our hospital for surgical
      treatment of heart valve disease. She required both mitral and aortic valve
      replacement with mechanical valves, associated with tricuspid annuloplasty. After
      aortic de-clamping, a massive hemorrhage from the posterior atrioventricular
      groove was observed. Under repeated cardiac arrest, the left atrium was reopened,
      the implanted mitral prosthetic valve was removed and a type I left ventricular
      rupture (Treasure classification) was diagnosed. The lesion was directly repaired
      with mattress stitches and running sutures, using reinforcement materials such as
      a glutaraldehyde-treated bovine pericardium. To avoid mechanical stress by the
      prosthetic valve on the repaired site, a mechanical valve was implanted using a
      translocation method. The patient suffered from aspiration pneumonia and disuse
      atrophy for 3 months. However, she was doing well at 1 year post-operation.

PMID- 25963783
TI  - [Aortic regurgitation with osteogenesis imperfecta].
AB  - A 49-year-old male was referred to our hospital for cardiomegaly and severe
      aortic regurgitation. He had been diagnosed with osteogenesis imperfecta (OI) due
      to his history of multiple fractures in childhood and blue sclera. Aortic valve
      replacement(AVR) was performed via femoral cannulation and full sternotomy, with
      the opening of the sternum limited to a width of 6-7 cm in order to protect the
      brittle sternum and thorax. After weaning the patient off cardiopulmonary bypass,
      the sternum was closed using titanium plates. He subsequently recovered without
      excessive bleeding or other complications, and the healing of the sternum 3
      months after the surgery was satisfactory. Cardiovascular surgery has been
      reported to be associated with high morbidity and mortality in patients with OI
      due to their friability of tissue and bleeding tendency. In the present case, AVR
      was performed successfully in a patient with OI using various surgical
      techniques. 

PMID- 25963784
TI  - [Hemoptysis caused by bleeding into a bleb].
AB  - A man in his 40s was admitted to our hospital for hemoptysis. A chest computed
      tomography showed a mediastinal mass adjacent to the left side wall of the
      ascending aorta with infiltrative shadows of the left upper lobe. In spite of
      medical treatment, hemoptysis continued, and the surgery was performed. The
      thoracoscopic findings showed hematoma in the bullous cavity. Partial resection
      of the left upper lobe was performed. Histopathological findings in the resected
      specimen revealed a bleb that was filled with blood. 

PMID- 25963785
TI  - [Patch plasty of intraoperative acute aortic dissection in a patient with severe
      aortic valve stenosis;report of a case].
AB  - Intraoperative aortic dissection is a rare complication, but is associated with a
      high mortality. We report a case of 79-year-old woman with severe aortic valve
      stenosis who underwent aortic valve replacement(AVR). After cardiopulmonary
      bypass(CPB) was established, aortic dissection started at the inflow cannulation
      site. Because hemodynamics were stable, we performed AVR as scheduled. After
      declamping, excessive bleeding from the arterial cannulation site continued. CPB
      was reestablished by placing the arterial cannula in the left femoral artery. The
      ascending aorta was opened at the site of cannulation under deep hypothermic
      circulatory arrest. The entry tear was successfully repaired by entry resection
      and Hemashield patch plasty. The postoperative course was uneventful, and the
      patient was discharged on the 22nd postoperative day. Patch plasty may be useful
      for the management of intraoperative aortic dissection. 

PMID- 25963786
TI  - [Distal Aortic Arch Aneurysm, Acute type B Aortic Dissection, and Acute Bilateral
      Limb Ischemia Treated by Two-stage Total Arch Replacement;Report of a Case].
AB  - A 74-year-old female patient experienced sudden and severe pain in her lower back
      and both legs. Upon examination, her femoral pulses were weak, and her legs were
      pale. Computed tomography revealed a 66-mm thoracic aneurysm in the distal arch
      and type B aortic dissection. Stenosis was present from the terminal aorta to the
      iliac arteries. The left common iliac artery was occluded at its bifurcation, and
      both lower limbs were ischemic. We performed bilateral axillary-femoral artery
      bypass, which improved blood flow to both limbs. The next day, it was apparent
      that compartment syndrome had developed in the patient's left leg. Rehabilitation
      therapy was effective for the compartment syndrome, the patient's symptoms
      resolved, and she was discharged. We later performed two-stage total arch
      replacement, and the subsequent clinical course has been without incident. 

PMID- 25963787
TI  - [DeBakey type 2 Aortic Dissection Failed to Diagnose by Enhanced Computed
      Tomography;Report of a Case].
AB  - An 81-year-old woman presented with dyspnea and chest pain. A plain chest X-ray
      revealed widening of the mediastinum and a contrast-enhanced chest computed
      tomography showed dilatation of the ascending aorta without any specific findings
      of aortic dissection. Transesophageal echocardiography revealed severe aortic
      regurgitation (AR). We planned an aortic valve replacement on the 34th day after
      admission because of the severe AR. During the operation, we found an entry in
      the intima of the ascending aorta 5 mm above the aortic valve and she was
      diagnosed with DeBakey type II aortic dissection. Therefore, we decided to
      perform Bentall's operation and the operation was successful. 

PMID- 25963788
TI  - [Surgical Treatment for Kommerell's Diverticulum with Aortic Dissection;Report of
      a Case].
AB  - A 43-year-old man was referred to our hospital with chest pain. Computed
      tomography revealed thrombosed type B aortic dissection and distal aortic arch
      aneurysm with maximum diameter of 56 mm accompanied by an aberrant right
      subclavian artery (Kommerell's diverticulum). After performing anti-hypertensive
      treatment, we planned surgical treatment the operation. Graft replacement of
      distal aortic arch aneurysm was performed through left posterolateral thoracotomy
      with deep hypothermic circulatory arrest. The aberrant right subclavian artery
      was reconstructed with an interposed graft. Postoperative course was uneventful
      and he was discharged on the 9th postoperative day. Kommerell's diverticulum with
      aortic dissection is a relatively rare condition. Here we describe our surgical
      strategy with a review of the literature. 

PMID- 25963789
TI  - [Prosthetic Valve Endocarditis using Immunosuppressive Agent for Atopic
      Dermatitis;Report of a Case].
AB  - A 26-year-old man had a history of severe atopic dermatitis. He was taking
      immunosuppressive drug. Mitral valve replacement (MVR) had been performed for
      infective endocarditis March 2008. He came to our hospital in July 2012
      complaining of fever of 39 degrees Celsius. According to computed tomography (CT)
      and transesophageal echocardiography (TEE), we diagnosed that he had cerebral
      embolism and bacterial infection of prosthetic valve. Antibiotic treatment was
      performed for 2 weeks after the onset of cerebral infarction. Then we conducted
      re-MVR. The postoperative course was satisfactory. He showed a gradual
      improvement in the level of consciousness and was discharged. In patients with
      atopic dermatitis, bacteria can penetrate into the blood from the skin easily. So
      they are often affected by bacteremia. There are some reports that infective
      endocarditis is likely to occur in immunosuppressed patients. It is suggested
      that immunosuppressive drug was involved in the development of prosthetic valve
      endocarditis (PVE) in addition to atopic dermatitis in this patient.

PMID- 25963790
TI  - [Mycotic Aneurysm of Distal Aortic Arch, after Total Arch Replacement with Open
      stent Graft;Report of a Case].
AB  - The patient was a 72-year-old man, who had undergone total arch replacement with
      an open-stent graft due to saccular aneurysm of distal arch, 2 years before. He
      was admitted to a local hospital with the complaint of high fever, and was
      diagnosed as having pyothorax, after computed tomography (CT) scanning. After
      transferred to our hospital, he was treated by drainage, and antibiotic therapy.
      But CT scans showed the enlargement of distal arch aneurysm, and migration of the
      stent graft. Urgent operation was performed. We approached to the site by a full
      sternotomy, and left anterolateral thoracotomy. Segment 1+2 of the left lung was
      resected to avoid bleeding and lung injury. Graft replacement of distal arch and
      descending aorta was performed on cardiopulmonary bypass, with hypothermia,
      selective brain perfusion and systemic circulatory arrest. To protect from
      recurrence of infection, the omental flap was transposed to the graft site. Until
      now, there is no recurrence of infection.

PMID- 25963791
TI  - [Thoracic Aortic Aneurysm due to Giant Cell Arteritis;Report of a Case].
AB  - A 70-year-old man with an ascending aortic aneurysm was referred to our hospital.
      He had not shown any head symptoms and blood tests did not indicate any
      inflammation. Ascending aortic replacement was performed under cardiopulmonary
      bypass. Pathologic examination of the aneurysm wall was diagnosed for giant cell
      arteritis( GCA). Aortic aneurysm due to GCA without no symptom was extremely
      rare. 

PMID- 25963792
TI  - [Pulmonary Clear Cell Type Squamous Cell Carcinoma that Required Differential
      Diagnosis from Metastatic Ureter Cancer;Report of a Case].
AB  - A 71-year-old woman was referred to our department for a nodular lesion in the
      left lung. She had been followed by urology department in our hospital for 6
      years since right nephrectomy for ureter cancer. Chest X-ray and computed
      tomography (CT) scan demonstrated a small nodular shadow in the left lower lobe.
      The lung tumor was removed by wedge resection, and pathologically diagnosed
      during the operation as a metastasis from the ureter cancer. The lung tumor
      consisted of clear cells similar to the ureter cancer. However, the final
      pathological diagnosis changed to a primary lung cancer based on the findings of
      stratified differentiation and cancer cell nests in the tumor.
      Immunohistochemical staining for ureter epithelium-related antigens confirmed the
      diagnosis. Although we recommended left lower completion lobectomy, the patient
      refused additional surgery. She is suspected to have local recurrence in the left
      lower lobe 18 months after the surgery.

PMID- 25963793
TI  - Deep sequencing reveals different compositions of mRNA transcribed from the F8
      gene in a panel of FVIII-producing CHO cell lines.
AB  - Coagulation factor VIII (FVIII) is one of the most complex biopharmaceuticals due
      to the large size, poor protein stability and extensive post-translational
      modifications. As a consequence, efficient production of FVIII in mammalian cells
      poses a major challenge, with typical yields two to three orders of magnitude
      lower than for antibodies. In the present study we investigated CHO DXB11 cells
      transfected with a plasmid encoding human coagulation factor VIII. Single cell
      clones were isolated from the pool of transfectants and a panel of 14 clones
      representing a dynamic range of FVIII productivities was selected for RNA
      sequencing analysis. The analysis showed distinct differences in F8 RNA
      composition between the clones. The exogenous F8-dhfr transcript was found to
      make up the most abundant transcript in the present clones. No correlation was
      seen between F8 mRNA levels and the measured FVIII productivity. It was found
      that three MTX resistant, nonproducing clones had different truncations of the F8
      transcripts. We find that by using deep sequencing, in contrast to microarray
      technology, for determining the transcriptome from CHO transfectants, we are able
      to accurately deduce the mature mRNA composition of the transgene and identify
      significant truncations that would probably otherwise have remained undetected. 

PMID- 25963794
TI  - Time to symptom improvement using elimination diets in non-IgE-mediated
      gastrointestinal food allergies.
AB  - BACKGROUND: The prevalence of food allergy has increased in recent decades, and
      there is paucity of data on time to symptom improvement using elimination diets
      in non-Immunoglobulin E (IgE)-mediated food allergies. We therefore aimed to
      assess the time required to improvement of symptoms using a symptom questionnaire
      for children with non-IgE-mediated food allergies on an elimination diet.
      METHODS: A prospective observational study was performed on patients with non-IgE
      mediated gastrointestinal food allergies on an elimination diet, who completed a
      questionnaire that includes nine evidence-based food allergic symptoms before and
      after the exclusion diet. The questionnaire measured symptoms individually from 0
      (no symptom) to 5 (most severe) and collectively from 0 to 45. Children were only
      enrolled in the study if collectively symptoms improved with the dietary
      elimination within 4 or 8 weeks. RESULTS: Data from 131 patients were analysed
      including 90 boys with a median age of 21 months [IQR: 7 to 66]. Based on the
      symptom questionnaire, 129 patients (98.4%) improved after 4-week elimination
      diet and only two patients improved after 8 weeks. A statistically significant
      difference before and after commencing the elimination diet was seen in all nine
      recorded symptoms (all p < 0.001), and in the median of overall score (p <
      0.001). CONCLUSION: This is the first study attempting to establish time to
      improve after commencing the diet elimination. Almost all children in this study
      improved within 4 weeks of following the elimination diet, under dietary
      supervision.

PMID- 25963795
TI  - Clinicopathological significance of cancer stem-like cell markers in high-grade
      neuroendocrine carcinoma of the lung.
AB  - PURPOSE: This study aimed to evaluate the clinicopathological significance of
      cancer stem-like cell (CSLC) markers in high-grade neuroendocrine carcinoma
      (HGNEC) of the lung, including small cell lung carcinoma (SCLC) and large cell
      neuroendocrine carcinoma (LCNEC). METHODS: We retrospectively studied patients
      who underwent surgical resection of SCLC (n = 60) and LCNEC (n = 45) to analyze
      their clinicopathological profiles and the immunohistochemical expression of
      putative CSLC markers (Caveolin, Notch, CD44, CD166, SOX2, ALDH1, and Musashi1).
      Staining scores for these markers in tumor cells were calculated by multiplying
      the percentage of positive tumor cells per lesion by the staining intensity level
      (0, 1, and 2); a score of >= 10 represented positive expression. RESULTS: There
      was a difference between SCLC and LCNEC with respect to both SOX2 (55 vs. 27 %, p
      = 0.003) and CD166 (27 vs. 47 %, p = 0.034) expression. ALDH1 expression was
      equally observed in SCLC and LCNEC (67 vs. 73 %, p = 0.46), and patients with
      ALDH1-positive HGNEC had significantly worse recurrence-free survival (RFS) and
      overall survival (OS) rates than those with ALDH1-negative HGNEC (5-year RFS: 39
      vs. 67 %, p = 0.009; 5-year OS: 50 vs. 79 %, p = 0.021). A multivariate analysis
      revealed that positive ALDH1 expression was an independent unfavorable prognostic
      factor with respect to both RFS and OS. CONCLUSIONS: The differences in the
      expression profiles of CSLC markers might reflect morphological differences
      between SCLC and LCNEC. Positive ALDH1 expression in lung HGNEC was associated
      with an unfavorable patient prognosis, which suggested that ALDH1-positive tumor
      cells might be future therapeutic targets for the treatment of lung HGNEC.

PMID- 25963796
TI  - Circulating gonadotropins and ovarian adiponectin system are modulated by
      acupuncture independently of sex steroid or beta-adrenergic action in a female
      hyperandrogenic rat model of polycystic ovary syndrome.
AB  - Acupuncture with combined manual and low-frequency electrical stimulation, or
      electroacupuncture (EA), reduces endocrine and reproductive dysfunction in women
      with polycystic ovary syndrome (PCOS), likely by modulating sympathetic nerve
      activity or sex steroid synthesis. To test this hypothesis, we induced PCOS in
      rats by prepubertal implantation of continuous-release letrozole pellets (200
      ug/day) or vehicle. Six weeks later, rats were treated for 5-6 weeks with low
      frequency EA 5 days/week, subcutaneous injection of 17beta-estradiol (2.0 ug)
      every fourth day, or a beta-adrenergic blocker (propranolol hydrochloride, 0.1
      mg/kg) 5 days/week. Letrozole controls were handled without needle insertion or
      injected with sesame oil every fourth day. Estrous cyclicity, ovarian morphology,
      sex steroids, gonadotropins, insulin-like growth factor I, bone mineral density,
      and gene and protein expression in ovarian tissue were measured. Low-frequency EA
      induced estrous-cycle changes, decreased high levels of circulating luteinizing
      hormone (LH) and the LH/follicle-stimulating hormone (FSH) ratio, decreased high
      ovarian gene expression of adiponectin receptor 2, and increased expression of
      adiponectin receptor 2 protein and phosphorylation of ERK1/2. EA also increased
      cortical bone mineral density. Propranolol decreased ovarian expression of Foxo3,
      Srd5a1, and Hif1a. Estradiol decreased circulating LH, induced estrous cycle
      changes, and decreased ovarian expression of Adipor1, Foxo3, and Pik3r1. Further,
      total bone mineral density was higher in the letrozole-estradiol group. Thus, EA
      modulates the circulating gonadotropin levels independently of sex steroids or
      beta-adrenergic action and affects the expression of ovarian adiponectin system.

PMID- 25963797
TI  - Molecular mechanisms underlying oxytocin-induced cardiomyocyte protection from
      simulated ischemia-reperfusion.
AB  - Oxytocin (OT) stimulates cardioprotection. Here we investigated heart-derived
      H9c2 cells in simulated ischemia-reperfusion (I-R) experiments in order to
      examine the mechanism of OT protection. I-R was induced in an anoxic chamber for
      2 hours and followed by 2 h of reperfusion. In comparison to normoxia, I-R
      resulted in decrease of formazan production by H9c2 cells to 63.5 +/- 1.7% (MTT
      assay) and in enhanced apoptosis from 1.7 +/- 0.3% to 2.8 +/- 0.4% (Tunel test).
      Using these assays it was observed that treatment with OT (1-500 nM) exerted
      significant protection during I-R, especially when OT was added at the time of
      ischemia or reperfusion. Using the CM-H2DCFDA probe we found that OT triggers a
      short-lived burst in reactive oxygen species (ROS) production in cells but
      reduces ROS production evoked by I-R. In cells treated with OT, Western-blot
      revealed the phosphorylation of Akt (Thr 308, p-Akt), eNOS and ERK 1/2.
      Microscopy showed translocation of p-Akt and eNOS into the nuclear and
      perinuclear area and NO production in cells treated with OT. The OT-induced
      protection against I-R was abrogated by an OT antagonist, the Pi3K inhibitor
      Wortmannin, the cGMP-dependent protein kinase (PKG) inhibitor, KT5823, as well as
      soluble guanylate cyclase (GC) inhibitor, ODQ, and particulate GC antagonist,
      A71915. In conditions of I-R, the cells with siRNA-mediated reduction in OT
      receptor (OTR) expression responded to OT treatment by enhanced apoptosis. In
      conclusion, the OTR protected H9c2 cells against I-R, especially if activated at
      the onset of ischemia or reperfusion. The OTR-transduced signals include pro
      survival kinases, such as Akt and PKG.

PMID- 25963798
TI  - alpha-Defensins partially protect human neutrophils against Panton-Valentine
      leukocidin produced by Staphylococcus aureus.
AB  - alpha-Defensins produced by neutrophils are important effector molecules of the
      innate immune system. In addition to their microbicidal effects, alpha-defensins
      have the ability to neutralize bacterial toxins. Panton-Valentine leukocidin
      (PVL) is the hallmark of community-acquired methicillin-resistant Staphylococcus
      aureus. Staphylococcus aureus that produce PVL are responsible for severe
      diseases, including necrotizing pneumonia. Polymorphonuclear neutrophils (PMNs)
      are the target cells of PVL action. The goal of this study was to elucidate the
      effect of a group of alpha-defensins known as the human neutrophil peptides
      (HNPs) on the interactions between LukS-PV and LukF-PV, which compose PVL, and
      human PMNs. We observed that HNPs bound to both subunits of PVL and significantly
      decreased PVL pore formation in PMNs, with a maximum inhibition of 27%. When
      various HNP molecules were tested individually under the same conditions, we
      observed that HNP3, but not HNP1 or 2, decreased pore formation. Similarly, HNP3
      significantly decreased PVL-induced PMN lysis, with a maximum inhibition of 31%.
      Interestingly, HNPs did not affect LukS-PV LukF-PV oligomerization, LukS-PV LukF
      PV binding to PMNs or calcium influx induced by PVL in PMNs. Our results suggest
      that HNP3 partially protects neutrophils against PVL by interfering with the
      conformational changes of PVL required to form a functional pore. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Panton-Valentine leukocidin (PVL) is a pore-forming
      toxin produced by Staphylococcus aureus, responsible for neutrophil damage and
      key player of severe staphylococcal diseases. Antimicrobial peptides produced by
      neutrophils (HNP1-3) neutralize several other bacterial cytotoxins. We examined
      the impact of human neutrophil peptides (HNPs) on PVL cytotoxicity against human
      neutrophils and we found that HNPs bind to both LukS and LukF components of PVL,
      thereby inhibiting pore formation and neutrophil lysis. Our results suggest that
      HNP3 may impair PVL conformational changes required to form a functional pore and
      provide insight into the pathogenesis of PVL-related staphylococcal infection,
      with potential impact on the disease outcome.

PMID- 25963799
TI  - Using the Repertory Grid Technique to Examine Trainee Clinical Psychologists'
      Construal of Their Personal and Professional Development.
AB  - : The repertory grid technique was used to explore how 26 third-year trainee
      clinical psychologists construed their personal and professional selves over the
      course of training and into the future. Each trainee completed a demographic
      questionnaire and a repertory grid with 10 elements: four 'personal self'
      elements, four 'professional self' elements and two 'qualified clinical
      psychologist' elements. They then rated the 10 elements on 10 bipolar constructs
      of their choosing. Trainees' personal and professional selves were construed to
      be similar to each other. Trainees had low self-esteem and reported currently
      feeling anxious, stressed, unsettled and lacking an appropriate work-life
      balance. These difficulties were attributed to the demands of training and were
      expected to resolve once training was completed with future selves being
      construed as similar to ideal selves. Suggestions for future research with
      improved methodology are made, and the implications of the findings for trainees,
      training providers and employers of newly qualified clinical psychologists are
      given. The overall implication being that stress in training is normative and the
      profession has a duty to normalize this and ensure that self-care and personal
      development are recognized as core competencies of the clinical psychologist for
      the benefit of its members and their clients. Copyright (c) 2015 John Wiley &
      Sons, Ltd. KEY PRACTITIONER MESSAGE: Clinical psychology trainees experience
      training as demanding and stressful, which negatively impacts on their personal
      and professional self-image and self-esteem. However, they are optimistic that
      they will become more like their ideal self in the future. Stress in clinical
      training (and beyond) is normative, and thus, personal development and self-care
      should be recognized as clinical psychologist's core competencies.

PMID- 25963800
TI  - PEGylated porcine glucagon-like peptide-2 improved the intestinal digestive
      function and prevented inflammation of weaning piglets challenged with LPS.
AB  - This study was conducted to determine the effects on intestinal function, anti
      inflammatory role and possible mechanism of polyethylene glycosylated (PEGylated)
      porcine glucagon-like peptide-2 (pGLP-2), a long-acting form of pGLP-2, in
      weaning piglets challenged with Escherichia coli lipopolysaccharide (LPS). We
      divided 18 weaned piglets on day 21 into three groups (control, LPS and LPS+PEG
      pGLP-2; n=6). The piglets from the LPS+PEG-pGLP-2 group were injected with PEG
      pGLP-2 at 10 nmol/kg BW from 5 to 7 days of the trials daily. On 8th day, the
      piglets in the LPS and LPS+PEG-pGLP-2 groups were intraperitoneally administered
      with 100 ug LPS/kg. The control group was administered with the same volume of
      saline solution. The piglets were then sacrificed on day 28. Afterwards, serum,
      duodenum, jejunum and ileum samples were collected for analysis of structural and
      functional endpoints. LPS+PEG-pGLP-2 treatment increased (P<0.05) lactase
      activities in the duodenum and the jejunum compared with LPS treatment. LPS+PEG
      pGLP-2 treatment also significantly increased sucrase activity in the jejunum
      compared with LPS treatment. Furthermore, LPS treatment increased (P<0.05) the
      mRNA expression levels of interleukin (IL)-8, tumour necrosis factor-alpha (TNF
      alpha) and IL-10 in the ileum compared with the control treatment. By contrast,
      LPS+PEG-pGLP-2 treatment decreased (P<0.05) the mRNA expression levels of IL-8,
      IL-10 and TNF-alpha in the ileum compared with the LPS treatment. LPS treatment
      also increased (P<0.05) the mRNA expression level of GLP-2 receptor (GLP-2R) and
      the percentage of GLP-2R-positive cells in the ileum; by comparison, these
      results were (P<0.05) reduced by LPS+PEG-pGLP-2 treatment. Moreover, LPS+PEG-pGLP
      2 treatment increased (P<0.05) the content of serum keratinocyte growth factor
      compared with the control group and the LPS group. The protective effects of PEG
      pGLP-2 on intestinal digestive function were associated with the release of GLP
      2R mediator (keratinocyte growth factor) and the decrease in the expressions of
      intestinal pro-inflammatory cytokines. 

PMID- 25963801
TI  - Screening of candidate genes in fibroblasts derived from patients with
      Dupuytren's contracture using bioinformatics analysis.
AB  - Our study aimed to identify candidate genes associated with Dupuytren's
      contracture (DC) and elucidate their roles in DC development. The microarray data
      of GSE21221 were downloaded from Gene Expression Omnibus database, including six
      samples from carpal tunnel-derived fibroblasts and six samples from DC-derived
      fibroblasts. The differentially expressed genes (DEGs) in DC samples were
      screened using limma package. GO annotation and KEGG pathway analyses were
      performed by DAVID online tool. Protein-protein interaction network and
      expression correlation network were constructed to identify crucial relationships
      between DEGs. Finally, candidate DC-associated genes were predicted based on
      comparative toxicogenomics database. A total of 529 DEGs (138 up- and 391 down
      regulated) in DC-derived fibroblasts were screened and compared with carpal
      tunnel-derived fibroblasts. Only ten DC-associated genes, such as neurotrophin 3
      (NTF3) and protein kinase C, epsilon (PRKCE), were further screened. In addition,
      NTF3 was significantly enriched in MAPK signaling pathway, in which other DEGs,
      such as nuclear receptor subfamily 4, group A, member 1 (NR4A1), fibroblast
      growth factor 22 (FGF22) and BDNF, were enriched. Besides, NTF3 could co-express
      with fibrillin 2 (FBN2), and PRKCE could co-express with zinc finger protein 516
      (ZNF516), solute carrier organic anion transporter family, member 2A1 (SLCO2A1),
      chromosome 10 open reading frame 10 (C10orf10) and Kelch domain containing 7A
      (KLHDC7A). Our study indicates that these DEGs, including NTF3, FBN2, NR4A1,
      FGF22, BDNF, PRKCE, ZNF516, SLCO2A1, C10orf10 and KLHDC7A, may play important
      roles in DC development and serve as candidate molecular targets for treating DC.

PMID- 25963803
TI  - Hepatocellular carcinoma risk in chronic hepatitis B virus-infected compensated
      cirrhosis patients with low viral load.
AB  - Controversy exists about whether antiviral therapy (AVT) should be recommended
      for compensated cirrhosis patients with chronic hepatitis B virus (HBV) infection
      and detectable, but low, serum HBV-DNA levels. A retrospective cohort of 385
      treatment-naive, HBV-related compensated cirrhosis patients (mean age: 51.1 +/-
      9.7 years; 66% male) with low HBV-DNA levels (<2,000 IU/mL) was assessed for the
      development of hepatocellular carcinoma (HCC). During a median of 5.6 years of
      follow-up, HCC had developed in 37 (9.6%) patients. The 5-year cumulative HCC
      incidence rate was 2.2%, 8.0%, and 14.0% for patients with undetectable HBV DNA
      (<12 IU/mL), low HBV-DNA levels plus normal alanine aminotransferase (ALT)
      levels, and low HBV-DNA levels plus elevated ALT levels at baseline (P = 0.011).
      During follow-up, 71 patients maintained undetectable HBV-DNA levels, and 126
      experienced HBV-DNA elevation over 2,000 IU/mL. AVT was initiated in 77 patients.
      In patients without AVT, the 5-year cumulative HCC incidence rates were 13.3%,
      8.8%, and 1.4% for those who experienced HBV-DNA elevation, those who maintained
      detectable, but low, HBV-DNA levels, and those who maintained undetectable HBV
      DNA levels, respectively. The 5-year cumulative HCC incidence rate was 5.9% for
      patients who started AVT; longer AVT duration and longer complete virological
      response (<12 IU/mL) duration was associated with lower HCC risk. CONCLUSION:
      Compensated cirrhosis patients with detectable, but low, viral load were not at
      low risk for HCC, and AVT was associated with lower HCC risk, suggesting that
      prompt AVT should be considered for these patients.

PMID- 25963802
TI  - Ultrasonographic measurement of carotid artery resistive index and diastolic
      function of the heart in gout patients.
AB  - The aim of the study was to establish the functional disorder in the blood
      circulation of gout patients with a method that shows early damage of the heart
      and vascular structures. A total of 117 patients were examined cross-sectionally
      by a complex multimodal ultrasonography and were divided into four groups: 37
      healthy controls, 24 asymptomatic hyperuricemia, 36 gout without tophi and 20
      gouty tophi. With pulsed Doppler, common carotid artery resistive index (CCARI)
      and parameters of the transmitral blood flow were determined: the ratio between
      maximal early and late flow velocities (E/A ratio) and deceleration time (DT).
      With tissue Doppler imaging, mitral annular peak velocity (Em) was obtained. In
      the examined ultrasonographic parameters between healthy controls and the three
      patient groups, there was a statistically significant difference (p < 0.001).
      Comparing asymptomatic hyperuricemia and gout without tophi, no significant
      difference in CCARI (p = 0.656), E/A ratio (p = 0.472), DT (p = 0.990) and Em (p
      = 0.488) was found. Gouty tophi in comparison with gout without tophi and
      asymptomatic hyperuricemia had significantly lower Em (mean +/- SD 0.07 +/- 0.02
      vs 0.09 +/- 0.03 vs 0.13 +/- 0.17) and significantly higher CCARI (mean +/- SD
      0.74 +/- 0.05 vs 0.70 +/- 0.05 vs 0.69 +/- 0.05). Further multiple logistic
      regression revealed that tophi increased subject's likelihood of having category
      of CCARI >= 0.7 with an OR = 10.91 (95 % CI 1.80-66.14, p = 0.009), while the
      category of Em < 0.08 m/s was influenced by renal insufficiency with an OR = 3.07
      (95 % CI 1.17-8.02, p = 0.022). Gouty tophi are associated with progression of
      arteriosclerotic-type vessel changes. Worsening of diastolic dysfunction of the
      heart is independently associated with renal insufficiency. In terms of CV risk,
      tophi are an indicator of its increase. 

PMID- 25963804
TI  - Anti-malarials are anti-cancers and vice versa - one arrow two sparrows.
AB  - Repurposing is the novel means of drug discovery in modern science due to its
      affordability, safety and availability. Here, we systematically discussed the
      efficacy and mode of action of multiple bioactive, synthetic compounds and their
      potential derivatives which are used to treat/prevent malaria and cancer. We have
      also discussed the detailed molecular pathway involved in anti-cancer
      potentiality of an anti-malarial drug and vice versa. Although the causative
      agents, pathophysiology and manifestation of both the diseases are different but
      special emphasis has been given on similar pathways governing disease
      manifestation and the drugs which act through deregulating those pathways.
      Finally, a future direction has been speculated to combat these two diseases by a
      single agent developed using nanotechnology. Extended combination and new
      formulation of existing drugs for one disease may lead to the discovery of drug
      for other diseases like an arrow for two sparrows. 

PMID- 25963805
TI  - The prognostic significance of PD-L1 in bladder cancer.
AB  - Immunotherapy is a promising strategy for the treatment of various types of
      cancer. An antibody that targets programmed death ligand-1 (PD-L1) pathway has
      been shown to be active towards various types of cancer, including melanoma and
      lung cancer. MPDL3280A, an anti-PD-L1 antibody, has shown clear clinical activity
      in PD-L1-overexpressing bladder cancer with an objective response rate of 40-50%,
      resulting in a breakthrough therapy designation granted by FDA. These events
      pronounce the importance of targeting the PD-L1 pathway in the treatment of
      bladder cancer. In the present study, we investigated the prognostic significance
      of the expression of three genes in the PD-L1 pathway, including PD-L1, B7.1 and
      PD-1, in three independent bladder cancer datasets in the Gene Expression Omnibus
      database. PD-L1, B7.1 and PD-1 were significantly associated with
      clinicopathological parameters indicative of a more aggressive phenotype of
      bladder cancer, such as a more advanced stage and a higher tumor grade. In
      addition, a high level expression of PD-L1 was associated with reduced patient
      survival. Of note, the combination of PD-L1 and B7.1 expression, but not other
      combinations of the three genes, were also able to predict patient survival. Our
      findings support the development of anti-PD-L1, which blocks PD-L1-PD-1 and B7.1
      PD-L1 interactions, in treatment of bladder cancer. The observations were
      consistent in the three independent bladder cancer datasets consisting of a total
      of 695 human bladder specimens. The datasets were then assessed and it was found
      that the expression levels of the chemokine CC-motif ligand (CCL), CCL3, CCL8 and
      CCL18, were correlated with the PD-L1 expression level, while ADAMTS13 was
      differentially expressed in patients with a different survival status (alive or
      deceased). Additional investigations are required to elucidate the role of these
      genes in the PD-L1-mediated immune system suppression and bladder cancer
      progression. In conclusion, findings of this study suggested that PD-L1 is an
      important prognostic marker and a therapeutic target for bladder cancer.

PMID- 25963806
TI  - Actual drug allergy during childhood: Five years' experience at a tertiary
      referral centre.
AB  - BACKGROUND: Drug hypersensitivity reactions (DHR) are common in the paediatric
      population, representing a public health problem. Recent studies have confirmed
      that the frequency of drug allergy is overestimated by both parents and
      physicians. The aim of this study is to determine the prevalence and risk factors
      of actual drug allergies in children admitted to a tertiary referral allergy
      centre. METHODS: Medical records covering the period of 2005-2010 of children
      with a history of DHR were reviewed. Demographic features of the patients and
      results of skin and drug provocation tests were noted. The European Network for
      Drug Allergy (ENDA) questionnaire was filled by using medical records and making
      phone calls with parents. RESULTS: Ninety-six patients with 140 DHRs were
      evaluated. Seventeen children had confirmed drug allergy by positive skin tests
      (n=11) and drug provocation tests (n=5). One patient underwent severe anaphylaxis
      and subsequent cardiac arrest during infusion of the drug, and therefore
      diagnostic tests were not performed. Actual drug allergy was more frequent in
      children with chronic diseases (58.8% vs. 26.5%, p=0.018) and histories of
      anaphylaxis during DHR (58.8% vs. 24%, p=0.001). The patients' history of
      anaphylaxis [OR: 5.789, 95%CI: 1.880-17.554, p=0.002], sweating [OR: 7.8, 95%CI:
      1.041-58.443, p=0.046] and dyspnoea [OR: 5.230, 95%CI: 1.836-14.894, p=0.002]
      during suspicious DHRs increased the risk for actual drug allergy. CONCLUSION:
      Actual drug allergy was determined in 17.7% of the patients with a suspicious
      DHR. Having a history of anaphylaxis during suspected drug reactions as well as
      symptoms of sweating and dyspnoea increased the risk for actual drug allergy.

PMID- 25963807
TI  - General Practitioners' knowledge and use of genetic counselling in managing
      patients with genetic cardiac disease in non-specialised settings.
AB  - There have been over 40 cardiac diseases with a genetic cause identified to date.
      The management of most genetic cardiac diseases (GCDs) now necessitates
      multidisciplinary care, including the provision of genetic counselling. This
      study investigated the knowledge and management of GCDs by General Practitioners
      (GPs). Questionnaires were mailed out to 685 doctors working in general practice
      in Tasmania, Australia, with 144 responses (21 %) received. Results showed that
      the majority (77.8 %) of the responding doctors are managing at least one patient
      with GCD in their practice. However, GPs identified having limited confidence in
      the appropriate management of these conditions and indicated that they are very
      dependent on guidance from a cardiologist, including whether to refer a patient
      to genetic counselling. To our knowledge, this is the first Australian study that
      looks at the care of patients with GCD in the primary care sector. The knowledge
      gained will help us provide more appropriate care for patients who do not have
      immediate access to specialised services, particularly those outside metropolitan
      areas, and provides evidence for what resources can be offered to doctors working
      in general practice to help provide quality care for these patients. 

PMID- 25963808
TI  - Kinetic study on the effect of temperature on biogas production using a lab scale
      batch reactor.
AB  - In the present study, biogas production from food waste through anaerobic
      digestion was carried out in a 2l laboratory-scale batch reactor operating at
      different temperatures with a hydraulic retention time of 30 days. The reactors
      were operated with a solid concentration of 7.5% of total solids and pH 7. The
      food wastes used in this experiment were subjected to characterization studies
      before and after digestion. Modified Gompertz model and Logistic model were used
      for kinetic study of biogas production. The kinetic parameters, biogas yield
      potential of the substrate (B), the maximum biogas production rate (Rb) and the
      duration of lag phase (lambda), coefficient of determination (R(2)) and root mean
      square error (RMSE) were estimated in each case. The effect of temperature on
      biogas production was evaluated experimentally and compared with the results of
      kinetic study. The results demonstrated that the reactor with operating
      temperature of 50 degrees C achieved maximum cumulative biogas production of
      7556ml with better biodegradation efficiency. 

PMID- 25963810
TI  - Clobazam: An effective add-on therapy in refractory status epilepticus.
AB  - Refractory status epilepticus (RSE) is a medical emergency, with significant
      morbidity and mortality. The use and effectiveness of clobazam, a unique 1,5
      benzodiazepine, in the management of RSE has not been reported before. Over the
      last 24 months, we identified 17 patients with RSE who were treated with clobazam
      in our hospital. Eleven of the 17 patients had prior epilepsy. Fifteen patients
      had focal status epilepticus. Use of clobazam was prompted by a favorable
      pharmacokinetic profile devoid of drug interactions. Clobazam was introduced
      after a median duration of 4 days and after a median of three failed
      antiepileptic drugs. A successful response, defined as termination of RSE within
      24 h of administration, without addition or modification of concurrent AED and
      with successful wean of anesthetic infusions, was seen in 13 patients.
      Indeterminate response was seen in three patients, whereas clobazam was
      unsuccessful in one patient. Clobazam averted the need for anesthetic infusions
      in five patients. Clobazam was well tolerated, and appears to be an effective and
      promising option as add-on therapy in RSE. Its efficacy, particularly early in
      the course of SE, should be further investigated in prospective, randomized
      trials.

PMID- 25963809
TI  - Effect of low doses of methamphetamine on rat limbic-related neurotensin systems.
AB  - Administration of methamphetamine (METH) alters limbic-related (LR) neurotensin
      (NT) systems. Thus, through a D1-receptor mechanism, noncontingent high doses (5
      15 mg kg(-1)), and likely self-administration, of METH appears to reduce NT
      release causing its accumulation and an elevation of NT-like immunoreactivity
      (NTLI) in limbic-related NT pathways. For comparison, we tested the effect of low
      doses of METH, that are more like those used in therapy, on NTLI in the core and
      shell of the nucleus accumbens (NAc and NAs), prefrontal cortex (PFC), ventral
      tegmental area (VTA), the lateral habenula (Hb) and basolateral amygdala (Amyg).
      METH at the dose of 0.25 mg kg(-1) in particular, but not 1.00 mg kg(-1),
      decreased NTLI concentration in all of the LR structures studied, except for the
      prefrontal cortex; however, these effects were rapid and brief being observed at
      5 h but not at 24 h after treatment. In all of the LR areas where NTLI levels
      were reduced after the low dose of METH, the effect was blocked by pretreatment
      with either a D1 or a D2 antagonist. Thus, opposite to high doses like those
      associated with abuse, the therapeutic-like low-dose METH treatment induced
      reduction in NT tissue levels likely reflected an increase in NT release and a
      short-term depletion of the levels of this neuropeptide in LR structures,
      manifesting features comparable to the response of basal ganglia NT systems to
      similar low doses of METH.

PMID- 25963812
TI  - In-silico search of virus-specific host microRNAs regulating avian influenza
      virus NS1 expression.
AB  - Avian influenza is a highly contagious viral infection caused by avian influenza
      virus type A of the family Orthomyxoviridae primarily affecting the avian
      species. The non-structural protein 1 (NS1) encoded by the NS1 gene of the virus
      is critical in establishing the infection. NS1 protein acts to suppress the virus
      induced host interferon response and also inhibit Protein kinase R activation
      thereby helping the virus to establish the infection. MicroRNAs (miRNA) are small
      regulatory endogenous non-coding RNAs of ~22 nucleotides in length located within
      introns of coding and non-coding genes, exons of non-coding genes or inter-genic
      regions. miRNAs can target the gene at various sites and effectively reduce or
      shut down its expression. In this study, set of differentially expressed chicken
      miRNA identified by deep sequencing H5N1 infected and SPF chicken lung were
      computationally analyzed, to identify targets in the NS1 gene. 300 differentially
      expressed miRNAs were then analyzed individually for target sites in
      gi|147667147|gb|EF362422.1| influenza A virus (A/chicken/India/NIV33487/06(H5N1))
      segment 8, complete sequence using RNAhybrid 2.2. The analysis yielded gga-miR
      1658* as the potential miRNA which is targeting the NS1 gene of H5N1 genome. 

PMID- 25963811
TI  - Cardiovascular Risk in Diabetes Mellitus: Complication of the Disease or of
      Antihyperglycemic Medications.
AB  - Cardiovascular disease is the principal complication and the leading cause of
      death for patients with diabetes (DM). The efficacy of antihyperglycemic
      treatments on cardiovascular disease risk remains uncertain. Cardiovascular risk
      factors are affected by antihyperglycemic medications, as are many intermediate
      markers of cardiovascular disease. Here we summarize the evidence assessing the
      cardiovascular effects of antihyperglycemic medications with regard to risk
      factors, intermediate markers of disease, and clinical outcomes. 

PMID- 25963813
TI  - Petra Schwille: Taking a minimalist approach to membranes.

PMID- 25963814
TI  - The shifting geography and language of cell biology.
AB  - With the increase in scientific activity globally, the geographical focus of
      basic research is shifting away from the West. At the same time,
      multidisciplinary approaches are uncovering new layers in our understanding of
      how cells work. How will these trends affect cell biology in the near future? 

PMID- 25963815
TI  - Megakaryocyte rupture for acute platelet needs.
AB  - Circulating platelets were thought to arise solely from the protrusion and
      fragmentation of megakaryocyte cytoplasm. Now, Nishimura et al. (2015. J. Cell
      Biol. http://dx.doi.org/10.1083/jcb.201410052) show that platelet release from
      megakaryocytes can be induced by interleukin-1alpha (IL-1alpha) via a new rupture
      mechanism, which yields higher platelet numbers, occurs independently of the key
      regulator of megakaryopoiesis thrombopoietin, and may occur during situations of
      acute platelet need. 

PMID- 25963817
TI  - Nek5 promotes centrosome integrity in interphase and loss of centrosome cohesion
      in mitosis.
AB  - Nek5 is a poorly characterized member of the NIMA-related kinase family, other
      members of which play roles in cell cycle progression and primary cilia function.
      Here, we show that Nek5, similar to Nek2, localizes to the proximal ends of
      centrioles. Depletion of Nek5 or overexpression of kinase-inactive Nek5 caused
      unscheduled separation of centrosomes in interphase, a phenotype also observed
      upon overexpression of active Nek2. However, separated centrosomes that resulted
      from Nek5 depletion remained relatively close together, exhibited excess
      recruitment of the centrosome linker protein rootletin, and had reduced levels of
      Nek2. In addition, Nek5 depletion led to loss of PCM components, including gamma
      tubulin, pericentrin, and Cdk5Rap2, with centrosomes exhibiting reduced
      microtubule nucleation. Upon mitotic entry, Nek5-depleted cells inappropriately
      retained centrosome linker components and exhibited delayed centrosome separation
      and defective chromosome segregation. Hence, Nek5 is required for the loss of
      centrosome linker proteins and enhanced microtubule nucleation that lead to
      timely centrosome separation and bipolar spindle formation in mitosis. 

PMID- 25963816
TI  - Cytoskeletal dynamics: a view from the membrane.
AB  - Many aspects of cytoskeletal assembly and dynamics can be recapitulated in vitro;
      yet, how the cytoskeleton integrates signals in vivo across cellular membranes is
      far less understood. Recent work has demonstrated that the membrane alone, or
      through membrane-associated proteins, can effect dynamic changes to the
      cytoskeleton, thereby impacting cell physiology. Having identified mechanistic
      links between membranes and the actin, microtubule, and septin cytoskeletons,
      these studies highlight the membrane's central role in coordinating these
      cytoskeletal systems to carry out essential processes, such as endocytosis,
      spindle positioning, and cellular compartmentalization. 

PMID- 25963818
TI  - Junctional actin assembly is mediated by Formin-like 2 downstream of Rac1.
AB  - Epithelial integrity is vitally important, and its deregulation causes early
      stage cancer. De novo formation of an adherens junction (AJ) between single
      epithelial cells requires coordinated, spatial actin dynamics, but the mechanisms
      steering nascent actin polymerization for cell-cell adhesion initiation are not
      well understood. Here we investigated real-time actin assembly during daughter
      cell-cell adhesion formation in human breast epithelial cells in 3D environments.
      We identify formin-like 2 (FMNL2) as being specifically required for actin
      assembly and turnover at newly formed cell-cell contacts as well as for human
      epithelial lumen formation. FMNL2 associates with components of the AJ complex
      involving Rac1 activity and the FMNL2 C terminus. Optogenetic control of Rac1 in
      living cells rapidly drove FMNL2 to epithelial cell-cell contact zones.
      Furthermore, Rac1-induced actin assembly and subsequent AJ formation critically
      depends on FMNL2. These data uncover FMNL2 as a driver for human epithelial AJ
      formation downstream of Rac1.

PMID- 25963819
TI  - Nucleocytoplasmic transport in the midzone membrane domain controls yeast mitotic
      spindle disassembly.
AB  - During each cell cycle, the mitotic spindle is efficiently assembled to achieve
      chromosome segregation and then rapidly disassembled as cells enter cytokinesis.
      Although much has been learned about assembly, how spindles disassemble at the
      end of mitosis remains unclear. Here we demonstrate that nucleocytoplasmic
      transport at the membrane domain surrounding the mitotic spindle midzone, here
      named the midzone membrane domain (MMD), is essential for spindle disassembly in
      Schizosaccharomyces pombe cells. We show that, during anaphase B, Imp1-mediated
      transport of the AAA-ATPase Cdc48 protein at the MMD allows this disassembly
      factor to localize at the spindle midzone, thereby promoting spindle midzone
      dissolution. Our findings illustrate how a separate membrane compartment supports
      spindle disassembly in the closed mitosis of fission yeast. 

PMID- 25963820
TI  - Nuclear-cytoskeletal linkages facilitate cross talk between the nucleus and
      intercellular adhesions.
AB  - The linker of nucleoskeleton and cytoskeleton (LINC) complex allows cells to
      actively control nuclear position by coupling the nucleus to the cytoplasmic
      cytoskeleton. Nuclear position responds to the formation of intercellular
      adhesions through coordination with the cytoskeleton, but it is not known whether
      this response impacts adhesion function. In this paper, we demonstrate that the
      LINC complex component SUN2 contributes to the mechanical integrity of
      intercellular adhesions between mammalian epidermal keratinocytes. Mice deficient
      for Sun2 exhibited irregular hair follicle intercellular adhesions, defective
      follicle structure, and alopecia. Primary mouse keratinocytes lacking Sun2
      displayed aberrant nuclear position in response to adhesion formation, altered
      desmosome distribution, and mechanically defective adhesions. This dysfunction
      appeared rooted in a failure of Sun2-null cells to reorganize their microtubule
      network to support coordinated intercellular adhesion. Together, these results
      suggest that cross talk between the nucleus, cytoskeleton, and intercellular
      adhesions is important for epidermal tissue integrity.

PMID- 25963821
TI  - Tau reduction prevents Abeta-induced axonal transport deficits by blocking
      activation of GSK3beta.
AB  - Axonal transport deficits in Alzheimer's disease (AD) are attributed to amyloid
      beta (Abeta) peptides and pathological forms of the microtubule-associated
      protein tau. Genetic ablation of tau prevents neuronal overexcitation and axonal
      transport deficits caused by recombinant Abeta oligomers. Relevance of these
      findings to naturally secreted Abeta and mechanisms underlying tau's enabling
      effect are unknown. Here we demonstrate deficits in anterograde axonal transport
      of mitochondria in primary neurons from transgenic mice expressing familial AD
      linked forms of human amyloid precursor protein. We show that these deficits
      depend on Abeta1-42 production and are prevented by tau reduction. The
      copathogenic effect of tau did not depend on its microtubule binding,
      interactions with Fyn, or potential role in neuronal development. Inhibition of
      neuronal activity, N-methyl-d-aspartate receptor function, or glycogen synthase
      kinase 3beta (GSK3beta) activity or expression also abolished Abeta-induced
      transport deficits. Tau ablation prevented Abeta-induced GSK3beta activation.
      Thus, tau allows Abeta oligomers to inhibit axonal transport through activation
      of GSK3beta, possibly by facilitating aberrant neuronal activity.

PMID- 25963822
TI  - IL-1alpha induces thrombopoiesis through megakaryocyte rupture in response to
      acute platelet needs.
AB  - Intravital visualization of thrombopoiesis revealed that formation of
      proplatelets, which are cytoplasmic protrusions in bone marrow megakaryocytes
      (MKs), is dominant in the steady state. However, it was unclear whether this is
      the only path to platelet biogenesis. We have identified an alternative MK
      rupture, which entails rapid cytoplasmic fragmentation and release of much larger
      numbers of platelets, primarily into blood vessels, which is morphologically and
      temporally different than typical FasL-induced apoptosis. Serum levels of the
      inflammatory cytokine IL-1alpha were acutely elevated after platelet loss or
      administration of an inflammatory stimulus to mice, whereas the MK-regulator
      thrombopoietin (TPO) was not elevated. Moreover, IL-1alpha administration rapidly
      induced MK rupture-dependent thrombopoiesis and increased platelet counts. IL
      1alpha-IL-1R1 signaling activated caspase-3, which reduced plasma membrane
      stability and appeared to inhibit regulated tubulin expression and proplatelet
      formation, and ultimately led to MK rupture. Collectively, it appears the balance
      between TPO and IL-1alpha determines the MK cellular programming for
      thrombopoiesis in response to acute and chronic platelet needs. 

PMID- 25963823
TI  - S-phase duration is the main target of cell cycle regulation in neural
      progenitors of developing ferret neocortex.
AB  - The evolutionary expansion of the neocortex primarily reflects increases in
      abundance and proliferative capacity of cortical progenitors and in the length of
      the neurogenic period during development. Cell cycle parameters of neocortical
      progenitors are an important determinant of cortical development. The ferret
      (Mustela putorius furo), a gyrencephalic mammal, has gained increasing importance
      as a model for studying corticogenesis. Here, we have studied the abundance,
      proliferation, and cell cycle parameters of different neural progenitor types,
      defined by their differential expression of the transcription factors Pax6 and
      Tbr2, in the various germinal zones of developing ferret neocortex. We focused
      our analyses on postnatal day 1, a late stage of cortical neurogenesis when upper
      layer neurons are produced. Based on cumulative 5-ethynyl-2'-deoxyuridine (EdU)
      labeling as well as Ki67 and proliferating cell nuclear antigen (PCNA)
      immunofluorescence, we determined the duration of the various cell cycle phases
      of the different neocortical progenitor subpopulations. Ferret neocortical
      progenitors were found to exhibit longer cell cycles than those of rodents and
      little variation in the duration of G1 among distinct progenitor types, also in
      contrast to rodents. Remarkably, the main difference in cell cycle parameters
      among the various progenitor types was the duration of S-phase, which became
      shorter as progenitors progressively changed transcription factor expression from
      patterns characteristic of self-renewal to those of neuron production. Hence, S
      phase duration emerges as major target of cell cycle regulation in cortical
      progenitors of this gyrencephalic mammal.

PMID- 25963824
TI  - Effect of water solvation on the lipophilicity of isomeric pyrimidine
      carboxamides.
AB  - Incorporation of nitrogen is a common medicinal chemistry tactic to reduce logD
      values. Neighboring group participation influences logD, so the results are
      isomer dependent. The logD and logP differences observed between isomeric
      pyrimidines 1, 2 and 3 presumably result when the carbonyl or ether lone pairs
      are in close proximity to a heterocyclic nitrogen lone pair, recruiting water to
      bridge between the electron rich atoms. Various lipophilicity calculators did not
      discriminate between 1 (logD=2.6) and 3 (logD=1.0), but solvation energies using
      Poisson-Boltzmann and 3D-RISM methods rationalize the observed differences in
      lipophilicity among pyrimidine carboxamide isomers.

PMID- 25963825
TI  - Initial development of a cytotoxic amino-seco-CBI warhead for delivery by prodrug
      systems.
AB  - Cyclopropabenzaindoles (CBIs) are exquisitely potent cytotoxins which bind and
      alkylate in the minor groove of DNA. They are not selective for cancer cells, so
      prodrugs are required. CBIs can be formed at physiological pH by Winstein
      cyclisation of 1-chloromethyl-3-substituted-5-hydroxy-2,3-dihydrobenzo[e]indoles
      (5-OH-seco-CBIs). Corresponding 5-NH2-seco-CBIs should also undergo Winstein
      cyclisation similarly. A key triply orthogonally protected intermediate on the
      route to 5-NH2-seco-CBIs has been synthesised, via selective
      monotrifluoroacetylation of naphthalene-1,3-diamine, Boc protection,
      electrophilic iodination, selective allylation at the trifluoroacetamide and 5
      exo radical ring-closure with TEMPO. This intermediate has potential for
      introduction of peptide prodrug masking units (deactivating the Winstein
      cyclisation and cytotoxicity), addition of diverse indole-amide side-chains
      (enhancing non-covalent binding prior to alkylation) and use of different leaving
      groups (replacing the usual chlorine, allowing tuning of the rate of Winstein
      cyclisation). This key intermediate was elaborated into a simple model 5-NH2-seco
      CBI with a dimethylaminoethoxyindole side-chain. Conversion to a bio-reactive
      entity and the bioactivity of this system were confirmed through DNA-melting
      studies (DeltaTm=13 degrees C) and cytotoxicity against LNCaP human prostate
      cancer cells (IC50=18nM).

PMID- 25963826
TI  - Molecular mechanisms of protein kinase regulation by calcium/calmodulin.
AB  - Many human protein kinases are regulated by the calcium-sensor protein
      calmodulin, which binds to a short flexible segment C-terminal to the enzyme's
      catalytic kinase domain. Our understanding of the molecular mechanism of kinase
      activity regulation by calcium/calmodulin has been advanced by the structures of
      two protein kinases-calmodulin kinase II and death-associated protein kinase 1
      bound to calcium/calmodulin. Comparison of these two structures reveals a
      surprising level of diversity in the overall kinase-calcium/calmodulin
      arrangement and functional readout of activity, as well as complementary
      mechanisms of kinase regulation such as phosphorylation.

PMID- 25963828
TI  - Hydrogel Encapsulation of Cells in Core-Shell Microcapsules for Cell Delivery.
AB  - A newly designed 3D core-shell microcapsule structure composed of a cell
      containing liquid core and an alginate hydrogel shell is fabricated using a
      coaxial dual-nozzle electrospinning system. Spherical alginate microcapsules are
      successfully generated with a core-shell structure and less than 300 MUm in
      average diameter using this system. The thickness of the core and shell can be
      easily controlled by manipulating the core and shell flow rates. Cells
      encapsulated in core-shell microcapsules demonstrate better cell encapsulation
      and immune protection than those encapsulated in microbeads. The observation of a
      high percentage of live cells (~80%) after encapsulation demonstrates that the
      voltage applied for generation of microcapsules does not significantly affect the
      viability of encapsulated cells. The viability of encapsulated cells does not
      change even after 3 d in culture, which suggests that the core-shell structure
      with culture medium in the core can maintain high cell survival by providing
      nutrients and oxygen to all cells. This newly designed core-shell structure can
      be extended to use in multifunctional platforms not only for delivery of cells
      but also for factor delivery, imaging, or diagnosis by loading other components
      in the core or shell. 

PMID- 25963829
TI  - Vascular brachytherapy versus drug-eluting stents in the treatment of in-stent
      restenosis: A meta-analysis of long-term outcomes.
AB  - INTRODUCTION: Clinical trials have shown a short-term benefit of drug-eluting
      stents (DES) compared to vascular brachytherapy (VBT) for treatment of in-stent
      restenosis (ISR). The long-term benefits of DES vs. VBT are conflicting in the
      literature. This study aimed to do a meta-analysis of long-term outcomes of DES
      compared to VBT for treatment of ISR. METHODS: PubMed, EMBASE, Cochrane Central
      and unpublished data were searched for cohort studies and randomized controlled
      trials (RCTs) that directly compared VBT to DES for the treatment of ISR. We
      evaluated the following outcomes at 2-5 years of follow-up: target lesion
      revascularization (TLR), target vessel revascularization (TVR), myocardial
      infarction (MI), stent thrombosis, cardiovascular (CV) mortality, and overall
      mortality. Heterogeneity was defined as I(2) values > 25%. Review Manager 5.1 was
      used for statistical analysis. RESULTS: We included 1,375 patients from five
      studies, of which three were RCTs. VBT was used to treat ISR in 685 (49.8%)
      patients. After a 2-5 year follow-up, no significant differences were found
      between treatment groups regarding MI (P = 0.49), stent thrombosis (P = 0.86), CV
      mortality (P = 0.35), and overall mortality (P = 0.71). TLR (OR 2.37; CI 1.55
      3.63; P < 0.001) and TVR (OR 2.23; CI 1.01-4.94; P = 0.05) were significantly
      increased in patients who received VBT. CONCLUSION: This study suggests that DES
      are associated with decreased long-term revascularization procedures when
      compared to VBT for the treatment of ISR. This benefit does not appear to be
      associated with a significant reduction in mortality or myocardial infarction.

PMID- 25963830
TI  - A web portal for in-silico action potential predictions.
AB  - INTRODUCTION: Multiple cardiac ion channels are prone to block by pharmaceutical
      compounds, and this can have large implications for cardiac safety. The effect of
      a compound on individual ion currents can now be measured in automated patch
      clamp screening assays. In-silico action potential models are proposed as one way
      of predicting the integrated compound effects on whole-cell electrophysiology, to
      provide an improved indication of pro-arrhythmic risk. METHODS: We have developed
      open source software to run cardiac electrophysiology simulations to predict the
      overall effect of compounds that block IKr, ICaL, INa, IKs, IK1 and Ito to
      varying degrees, using a choice of mathematical electrophysiology models. To
      enable safety pharmacology teams to run and evaluate these simulations easily, we
      have also developed an open source web portal interface to this simulator.
      RESULTS: The web portal can be found at
      https://chaste.cs.ox.ac.uk/ActionPotential. Users can enter details of compound
      affinities for ion channels in the form of IC50 or pIC50 values, run simulations,
      store the results for later retrieval, view summary graphs of the results, and
      export data to a spreadsheet format. DISCUSSION: This web portal provides a
      simple interface to reference versions of mathematical models, and well-tested
      state-of-the-art equation solvers. It provides safety teams easy access to the
      emerging technology of cardiac electrophysiology simulations for use in the drug
      discovery process.

PMID- 25963831
TI  - Alloimmunization is associated with older age of transfused red blood cells in
      sickle cell disease.
AB  - Red blood cell (RBC) alloimmunization is a significant clinical complication of
      sickle cell disease (SCD). It can lead to difficulty with cross-matching for
      future transfusions and may sometimes trigger life-threatening delayed hemolytic
      transfusion reactions. We conducted a retrospective study to explore the
      association of clinical complications and age of RBC with alloimmunization in
      patients with SCD followed at a single institution from 2005 to 2012. One hundred
      and sixty six patients with a total of 488 RBC transfusions were evaluated.
      Nineteen patients (11%) developed new alloantibodies following blood transfusions
      during the period of review. The median age of RBC units was 20 days
      (interquartile range: 14-27 days). RBC antibody formation was significantly
      associated with the age of RBC units (P = 0.002), with a hazard ratio of 3.5 (95%
      CI: 1.71-7.11) for a RBC unit that was 7 days old and 9.8 (95% CI: 2.66-35.97)
      for a unit that was 35 days old, 28 days after the blood transfusion. No
      association was observed between RBC alloimmunization and acute vaso-occlusive
      complications. Although increased echocardiography-derived tricuspid regurgitant
      jet velocity (TRV) was associated with the presence of RBC alloantibodies (P =
      0.02), TRV was not significantly associated with alloimmunization when adjusted
      for patient age and number of transfused RBC units. Our study suggests that RBC
      antibody formation is significantly associated with older age of RBCs at the time
      of transfusion. Prospective studies in patients with SCD are required to confirm
      this finding.

PMID- 25963832
TI  - Conformational rearrangements in the transmembrane domain of CNGA1 channels
      revealed by single-molecule force spectroscopy.
AB  - Cyclic nucleotide-gated (CNG) channels are activated by binding of cyclic
      nucleotides. Although structural studies have identified the channel pore and
      selectivity filter, conformation changes associated with gating remain poorly
      understood. Here we combine single-molecule force spectroscopy (SMFS) with
      mutagenesis, bioinformatics and electrophysiology to study conformational changes
      associated with gating. By expressing functional channels with SMFS fingerprints
      in Xenopus laevis oocytes, we were able to investigate gating of CNGA1 in a
      physiological-like membrane. Force spectra determined that the S4 transmembrane
      domain is mechanically coupled to S5 in the closed state, but S3 in the open
      state. We also show there are multiple pathways for the unfolding of the
      transmembrane domains, probably caused by a different degree of alpha-helix
      folding. This approach demonstrates that CNG transmembrane domains have dynamic
      structure and establishes SMFS as a tool for probing conformational change in ion
      channels. 

PMID- 25963833
TI  - Quantitative Proteomics Reveals Dynamic Interactions of the Minichromosome
      Maintenance Complex (MCM) in the Cellular Response to Etoposide Induced DNA
      Damage.
AB  - The minichromosome maintenance complex (MCM) proteins are required for processive
      DNA replication and are a target of S-phase checkpoints. The eukaryotic MCM
      complex consists of six proteins (MCM2-7) that form a heterohexameric ring with
      DNA helicase activity, which is loaded on chromatin to form the pre-replication
      complex. Upon entry in S phase, the helicase is activated and opens the DNA
      duplex to recruit DNA polymerases at the replication fork. The MCM complex thus
      plays a crucial role during DNA replication, but recent work suggests that MCM
      proteins could also be involved in DNA repair. Here, we employed a combination of
      stable isotope labeling with amino acids in cell culture (SILAC)-based
      quantitative proteomics with immunoprecipitation of green fluorescent protein
      tagged fusion proteins to identify proteins interacting with the MCM complex, and
      quantify changes in interactions in response to DNA damage. Interestingly, the
      MCM complex showed very dynamic changes in interaction with proteins such as
      Importin7, the histone chaperone ASF1, and the Chromodomain helicase DNA binding
      protein 3 (CHD3) following DNA damage. These changes in interactions were
      accompanied by an increase in phosphorylation and ubiquitination on specific
      sites on the MCM proteins and an increase in the co-localization of the MCM
      complex with gamma-H2AX, confirming the recruitment of these proteins to sites of
      DNA damage. In summary, our data indicate that the MCM proteins is involved in
      chromatin remodeling in response to DNA damage. 

PMID- 25963834
TI  - Global Proteomics Analysis of the Response to Starvation in C. elegans.
AB  - Periodic starvation of animals induces large shifts in metabolism but may also
      influence many other cellular systems and can lead to adaption to prolonged
      starvation conditions. To date, there is limited understanding of how starvation
      affects gene expression, particularly at the protein level. Here, we have used
      mass-spectrometry-based quantitative proteomics to identify global changes in the
      Caenorhabditis elegans proteome due to acute starvation of young adult animals.
      Measuring changes in the abundance of over 5,000 proteins, we show that acute
      starvation rapidly alters the levels of hundreds of proteins, many involved in
      central metabolic pathways, highlighting key regulatory responses. Surprisingly,
      we also detect changes in the abundance of chromatin-associated proteins,
      including specific linker histones, histone variants, and histone
      posttranslational modifications associated with the epigenetic control of gene
      expression. To maximize community access to these data, they are presented in an
      online searchable database, the Encyclopedia of Proteome Dynamics
      (http://www.peptracker.com/epd/). 

PMID- 25963836
TI  - Molecular Dynamics Simulation Analysis of Anti-MUC1 Aptamer and Mucin 1 Peptide
      Binding.
AB  - Aptasensors utilize aptamers as bioreceptors. Aptamers are highly efficient, have
      a high specificity and are reusable. Within the biosensor the aptamers are
      immobilized to maximize their access to target molecules. Knowledge of the
      orientation and location of the aptamer and peptide during binding could be
      gained through computational modeling. Experimentally, the aptamer (anti-MUC1
      S2.2) has been identified as a bioreceptor for breast cancer biomarker mucin 1
      (MUC1) protein. However, within this protein lie several peptide variants with
      the common sequence APDTRPAP that are targeted by the aptamer. Understanding
      orientation and location of the binding region for a peptide-aptamer complex is
      critical in their biosensor applicability. In this study, we investigate through
      computational modeling how this peptide sequence and its minor variants affect
      the peptide-aptamer complex binding. We use molecular dynamics simulations to
      study multiple peptide-aptamer systems consisting of MUC1 (APDTRPAP) and MUC1-G
      (APDTRPAPG) peptides with the anti-MUC1 aptamer under similar physiological
      conditions reported experimentally. Multiple simulations of the MUC1 peptide and
      aptamer reveal that the peptide interacts between 3' and 5' ends of the aptamer
      but does not fully bind. Multiple simulations of the MUC1-G peptide indicate
      consistent binding with the thymine loop of the aptamer, initiated by the
      arginine residue of the peptide. We find that the binding event induces
      structural changes in the aptamer by altering the number of hydrogen bonds within
      the aptamer and establishes a stable peptide-aptamer complex. In all MUC1-G cases
      the occurrence of binding was confirmed by systematically studying the distance
      distributions between peptide and aptamers. These results are found to
      corroborate well with experimental study reported in the literature that
      indicated a strong binding in the case of MUC1-G peptide and anti-MUC1 aptamer.
      Present MD simulations highlight the role of the arginine residue of MUC1-G
      peptide in initiating the binding. The addition of the glycine residue to the
      peptide, as in the case of MUC1-G, is shown to yield a stable binding. Our study
      clearly demonstrates the ability of MD simulations to obtain molecular insights
      for peptide-aptamer binding, and to provide details on the orientation and
      location of binding between the peptide-aptamer that can be instrumental in
      biosensor development. 

PMID- 25963835
TI  - Cell Surface Proteomics Provides Insight into Stage-Specific Remodeling of the
      Host-Parasite Interface in Trypanosoma brucei.
AB  - African trypanosomes are devastating human and animal pathogens transmitted by
      tsetse flies between mammalian hosts. The trypanosome surface forms a critical
      host interface that is essential for sensing and adapting to diverse host
      environments. However, trypanosome surface protein composition and diversity
      remain largely unknown. Here, we use surface labeling, affinity purification, and
      proteomic analyses to describe cell surface proteomes from insect-stage and
      mammalian bloodstream-stage Trypanosoma brucei. The cell surface proteomes
      contain most previously characterized surface proteins. We additionally identify
      a substantial number of novel proteins, whose functions are unknown, indicating
      the parasite surface proteome is larger and more diverse than generally
      appreciated. We also show stage-specific expression for individual paralogs
      within several protein families, suggesting that fine-tuned remodeling of the
      parasite surface allows adaptation to diverse host environments, while still
      fulfilling universally essential cellular needs. Our surface proteome analyses
      complement existing transcriptomic, proteomic, and in silico analyses by
      highlighting proteins that are surface-exposed and thereby provide a major step
      forward in defining the host-parasite interface. 

PMID- 25963838
TI  - Sibling perceptions of living with a young person with Down syndrome or autism
      spectrum disorder: an integrated review.
AB  - PURPOSE: This integrative review synthesized current information from 28 research
      articles meeting inclusion criteria that examined sibling experiences when living
      with a young person with Down syndrome or autism spectrum disorder. CONCLUSIONS:
      Five themes emerged related to sibling experiences: their knowledge of the
      condition, relationships with others, perceptions of the condition, emotional
      reactions to the situation, and behavioral/personality outcomes. PRACTICE
      IMPLICATIONS: Nurses caring for families raising youth with Down syndrome or
      autism spectrum disorder can enhance sibling development by providing individual
      interventions reflecting siblings' perceptions of the experience.

PMID- 25963837
TI  - Coincidental pituitary adenoma and planum sphenoidale meningioma mimicking a
      single tumor.

PMID- 25963839
TI  - A survey of the venom of the spider Lycosa vittata by biochemical,
      pharmacological and transcriptomic analyses.
AB  - Lycosa vittata, mainly distributed in the southwest of China, is a medium-sized
      and venomous spider, whose venom remains unexplored so far. This study aims to
      present an overview of the venom. It mainly consisted of diverse peptides and
      exhibited inhibitory effects on voltage-gated ion channels in rat dorsal root
      ganglia neurons, with a strongest inhibition on tetrodotoxin-sensitive and
      tetrodotoxin-resistant voltage-gated Na(+) channels. Interestingly, it exerted
      cytotoxicity to cancer cells, with approximately 10-fold selectivity on PC-3 over
      others, implying the existence of selective anti-PC-3 agents in the venom.
      Moreover, 51 toxin-like peptides were deduced from the venom gland transcriptome.
      Bioinformatic analyses suggested their structures might have some distinguished
      properties and their predicted functions were consistent with the venom
      activities. This study suggests that the venom is an attractive source of
      neurotoxins with therapeutic significance, and provides references for the
      structure and function investigation of specific toxins in the future. 

PMID- 25963840
TI  - Identification and evaluation of metastasis-related proteins, oxysterol binding
      protein-like 5 and calumenin, in lung tumors.
AB  - Metastasis is an important prognosis factor in lung cancer, therefore, it is
      imperative to identify target molecules and elucidate molecular mechanism of
      metastasis for developing new therapeutics and diagnosis methods. We searched for
      metastasis-related proteins by utilizing a novel antibody proteome technology
      developed in our laboratory that facilitated efficient screening of useful target
      proteins. Two-dimensional differential in-gel electrophoresis (2D-DIGE) analysis
      identified sixteen proteins, which were highly expressed in metastatic lung
      cancer cells, as protein candidates. Monoclonal single-chain variable fragments
      (scFvs) binding to candidates were isolated from a scFv-displaying phage library
      by affinity selection. Tissue microarray analysis of scFvs binding to candidates
      revealed that oxysterol binding protein-like 5 (OSBPL5) and calumenin (CALU) were
      expressed at a significantly higher levels in the lung tissues of metastasis
      positive cases than that in the metastasis-negative cases (OSBPL5; p=0.0156,
      CALU; p=0.0055). Furthermore, 80% of OSBPL5 and CALU double-positive cases were
      positive for lymph node metastasis. Consistent with these observations,
      overexpression of OSBPL5 and CALU promoted invasiveness of lung cancer cells.
      Conversely, knockdown of these proteins using respective siRNAs reversed the
      invasiveness of the lung cancer cells. Moreover, these proteins were expressed in
      lung tumor tissues, but not in normal lung tissues. In conclusion, OSBPL5 and
      CALU are related to metastatic potential of lung cancer cells, and they could be
      useful targets for cancer diagnosis and also for development of drugs against
      metastasis.

PMID- 25963841
TI  - Effect of active vitamin D on cardiovascular outcomes in predialysis chronic
      kidney diseases: A systematic review and meta-analysis.
AB  - AIM: Vitamin D deficient patients present an increased risk of cardiovascular
      disease. We conducted this systematic review and meta-analysis to evaluate the
      effect of active vitamin D analogue on cardiovascular outcomes in predialysis
      chronic kidney disease. METHODS: Pubmed, Embase, the Cochrane Library, CNKI, and
      article reference lists were searched for randomized controlled trials (RCTs)
      that compared active vitamin D analogues with placebo or no treatment for
      patients with predialysis chronic kidney disease. A meta-analysis was conducted
      using the standard methods consistent with the Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Reviewer Manager
      Software, ver. 5.2, was used. RESULTS: Seven RCTs (five studies with paricalcitol
      and two studies with calcitriol, 731 patients) were included. Compared with
      control groups, active vitamin D reduced the incidence of cardiovascular events
      (RR, 0.27; 95% CI, 0.13-0.59), induced an increase in those with proteinuria
      reduction (RR, 1.9; 95% CI, 1.34-2.71), but did not alter left ventricular mass
      index and systolic function (MD, 0.42 g/m2.7 ; 95% CI, -0.23-1.07 g/m2.7 , P =
      0.21 for left ventricular mass index and MD, -0.33; 95% CI, -0.74-0.07, P = 0.1
      for left ventricular ejection fraction). Neither systolic blood pressure nor
      diastolic blood pressure was reduced by active vitamin D (MD, 0.3 mmHg; 95% CI, 
      4.95-5.56 mmHg; MD, -0.24 mmHg; 95% CI: -6.21-5.72 mmHg, respectively). Increased
      probability of hypercalcaemia after paricalcitol therapy was found (RR, 7.85; 95%
      CI, 2.92-21.10). CONCLUSION: Active vitamin D reduced the incidence of
      cardiovascular events and induced a reduction in proteinuria, but its long-term
      effect on cardiac structure and function needed further confirmation. Increased
      probability of hypercalcaemia after paricalcitol therapy was found.

PMID- 25963842
TI  - Association of PTPN22 rs2476601 and STAT4 rs7574865 polymorphisms with rheumatoid
      arthritis: A meta-analysis update.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a common autoimmune disease with a
      complex genetic background. The genes encoding protein tyrosine phosphatase non
      receptor type 22 (PTPN22) and signal transducer and activator of transcription 4
      (STAT4) have been reported to be associated with RA in several ethnic
      populations. OBJECTIVES: This work aims to assess the association between PTPN22
      rs2476601 and STAT4 rs7574865 polymorphisms with RA susceptibility through an
      updated meta-analysis of available case-control studies. METHODS: A literature
      search of all relevant studies published from January 2007 up to December 2014
      was conducted using Pubmed and Science Direct databases. The observed studies
      that were related to an association between PTPN22 rs2476601 and STAT4 rs7574865
      polymorphisms with RA susceptibility were identified. Meta-analysis of the pooled
      and stratified data was done and assessed using varied genetic models. RESULTS:
      Thirty-seven case-control studies with a total of 47 comparisons (29 for PTPN22
      rs2476601 polymorphism and 18 for STAT4 rs7574865 polymorphism) met our inclusion
      criteria. The meta-analysis showed an association between PTPN22 T allele, CT+TT
      and TT genotypes with RA susceptibility. Furthermore, The meta-analysis showed an
      association between STAT4 T allele, GT+TT and TT genotypes with RA
      susceptibility. Stratification of RA patients according to ethnic groups showed
      that PTPN22 T allele, CT+TT genotypes, STAT4 T allele and STAT4 GT+TT were
      significantly associated with RA in European, Asian, African subjects, while
      PTPN22 TT genotype was significantly associated with RA in European but not in
      Asian and African subjects and STAT4 TT genotype was significantly associated
      with RA in European and Asian but not in African subject. A subgroup analysis
      according to the presence or absence of rheumatoid factor (RF) and anti-cyclic
      citrullinated peptide (anti-CCP) antibodies revealed that the association between
      PTPN22 rs2476601 and STAT4 rs7574865 polymorphisms with RA susceptibility may not
      be dependent on RF and anti-CCP antibodies. CONCLUSIONS: Our meta-analysis
      demonstrated that PTPN22 rs2476601 and STAT4 rs7574865 polymorphisms confers
      susceptibility to RA in total subjects and in major ethnic groups. The
      association may not be dependent on RF and anti-CCP antibodies.

PMID- 25963843
TI  - Effects of dietary cellulase and xylanase addition on digestion, rumen
      fermentation and methane emission in growing goats.
AB  - The objective of this study was to evaluate the effectiveness of supplementation
      of cellulase and xylanase to diets of growing goats to improve nutrient
      digestibility, utilisation of energy and mitigation of enteric methane emissions.
      The experiment was conducted in a 5 * 5 Latin square design using five goats with
      permanent rumen fistulae and five treatments consisted of two levels of cellulase
      crossed over with two levels of xylanase plus unsupplemented Control. The
      cellulase (243 U/g) derived from Neocallimastix patriciarum was added at 0.8 and
      1.6 g/kg dry matter intake (DMI) and the xylanase (31,457 U/ml) derived from
      Aspergillus oryzae was fed at 1.4 and 2.2 ml/kg DMI. There were no differences in
      apparent digestibility of organic matter, neutral detergent fibre, acid detergent
      fibre and rumen fermentation parameters (i.e. ammonia-nitrogen [N], volatile
      fatty acids) among all treatments. Dietary cellulase and xylanase addition did
      not influence energy and N utilisation. But compared to xylanase addition at the
      higher dose, at the low xylanase dose the retained N, the availability of
      retained N and digested N were increased (p < 0.01). Moreover, enzyme addition
      did not affect the enteric methane emission and community diversity of ruminal
      methanogens. The present results indicated that previous in vitro findings were
      not confirmed in ruminant trials.

PMID- 25963844
TI  - One-Dimensional Dielectric/Metallic Hybrid Materials for Photonic Applications.
AB  - Explorations of 1D nanostructures have led to great progress in the area of
      nanophotonics in the past decades. Based on either dielectric or metallic
      materials, a variety of 1D photonic devices have been developed, such as
      nanolasers, waveguides, optical switches, and routers. What's interesting is that
      these dielectric systems enjoy low propagation losses and usually possess active
      optical performance, but they have a diffraction-limited field confinement.
      Alternatively, metallic systems can guide light on deep subwavelength scales, but
      they suffer from high metallic absorption and can work as passive devices only.
      Thus, the idea to construct a hybrid system that combines the merits of both
      dielectric and metallic materials was proposed. To date, unprecedented optical
      properties have been achieved in various 1D hybrid systems, which manifest great
      potential for functional nanophotonic devices. Here, the focus is on recent
      advances in 1D dielectric/metallic hybrid systems, with a special emphasis on
      novel structure design, rational fabrication techniques, unique performance, as
      well as their wide application in photonic components. Gaining a better
      understanding of hybrid systems would benefit the design of nanophotonic
      components aimed at optical information processing. 

PMID- 25963845
TI  - Characterization of the distribution of rotational torque on electrorotation
      chips with 3D electrodes.
AB  - This is a study of in-plane and out-of-plane distribution of rotational torque
      (ROT-T) and effective electric field (EEF) on electrorotation (ER) devices with
      3D electrodes using finite element modeling (FEM) and experimental method. The
      objective of this study is to investigate electrical characteristics of the ER
      devices with five different electrode geometries and obtain an optimum structure
      for ER experiments. Further, it provides a comparison between characteristics of
      the 3D electrodes and traditionally used 2D electrodes. 3D distributions of EEF
      were studied by the time-variant FEM. FEM results were verified experimentally by
      studying the rotation of biological cells. The results show that the variations
      of ROT-T and EEF over the measurement area of the devices are considerably large.
      This can potentially lead to misinterpretation of recorded data. Therefore, it is
      essential to specify the boundaries of the measurement area with minimum
      deviation from the central EEF. For this purpose, FE analyses were utilized to
      specify the optimal region. Thereby, with confining the measurements to these
      regions, the dependency of ROT-T on the spatial position of the particles can be
      eliminated. Comparisons have been made on the sustainability of the EEF and ROT-T
      distributions for each device, to find an optimum design. Analyses of the devices
      prove that utilization of the 3D electrodes eliminate irregularities of EEF and
      ROT-T along the z-axis. The Results show that triangular electrodes provide the
      highest sustainability for the in-plane ROT-T and EEF distribution, while the
      oblate elliptical and circular electrodes have the lowest variances along the z
      axis. 

PMID- 25963846
TI  - Health benefits of endurance training alone or combined with diet for obese
      patients over 60: a review.
AB  - BACKGROUND: The prevalence of obesity is rapidly increasing in older patients and
      it is ubiquitous in many developed countries. Obesity is related to various
      negative health outcomes, making it a major public health target for
      intervention. PURPOSE: The aim of this study was to explore and summarise the
      literature that addresses endurance training alone or combined with nutrition
      interventions to combat obesity in obese patients over age 60. METHODS: We
      searched online electronic databases up to September 2014 for original
      observational and intervention studies published between 1995 and 2014 on the
      relationship between endurance training alone or combined with a diet in obese
      patients over 60 regarding health outcomes. RESULTS: Twenty-six studies examined
      interventions aimed specifically at promoting endurance training alone or
      combined with diet for older obese patients over 60. These studies demonstrated a
      positive effect of this intervention on the primary prevention of cardiovascular
      disease, and a significant beneficial effect on the lipid profile. Improvement of
      body composition and insulin sensitivity, and a reduction in blood pressure were
      also well established. CONCLUSIONS: Overall, this review demonstrates a positive
      effect of endurance training alone or combined with diet on health outcomes and
      metabolic benefits in older adults. Clinicians can now use this evidence to
      formulate actions to encourage the older obese to profit from the health benefits
      of endurance training and diet. This will not only help reduce the dramatic
      increase in the number of older obese but also help prevent sarcopenic obesity,
      which is a complex challenge for healthcare professionals.

PMID- 25963847
TI  - Erratum to: The Role of Collagen Organization on the Properties of Bone.

PMID- 25963848
TI  - Obesity-related changes in bone structural and material properties in hyperphagic
      OLETF rats and protection by voluntary wheel running.
AB  - PURPOSE: To examine how the development of obesity and the associated insulin
      resistance affect bone structural and material properties, and bone formation and
      resorption markers in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat model.
      METHODS: This was a 36-week study of sedentary, hyperphagic, male OLETF rats
      (OLETF-SED), exercise-treated OLETF rats (OLETF-EX) and sedentary non-hyperphagic
      controls (LETO-SED) with data collection at 13, 20, and 40 weeks of age (n = 5-8
      animals per group per timepoint). RESULTS: Body mass and fat (%) were
      significantly greater in OLETF-SED versus controls. OLETF-SED were insulin
      resistant at 13 and 20 weeks, with overt diabetes by 40 weeks. At 13weeks, OLETF
      SED had lower total body BMC and BMD and serum P1NP compared with LETO-SED.
      Differences in total body BMC and BMD between OLETF-SED and LETO-SED persisted at
      20 weeks, with reductions in total and cortical BMD of the tibia. OLETF-SED also
      had lesser femur diameter, cross-sectional area, polar moment of area, and torque
      at fracture than LETO-SED. By 40 weeks, OLETF-SED had elevated bone resorption
      and reduced intrinsic bone strength. OLETF-EX did not show the excessive weight
      gain, obesity, insulin resistance or diabetes observed in OLETF-SED. OLETF-EX had
      greater BMD than OLETF-SED, and structural and material properties of the femur
      were significantly increased in OLETF-EX relative to OLETF-SED and LETO-SED.
      CONCLUSIONS: The negative skeletal effects of excessive adiposity and insulin
      resistance were evident early in the progressive obesity with lasting negative
      impacts on intrinsic and extrinsic bone strength. Exercise protected against
      obesity-associated skeletal changes with marked benefits on the biomechanical
      properties of bone.

PMID- 25963849
TI  - Validation of the Dutch Aging Perceptions Questionnaire and development of a
      short version.
AB  - BACKGROUND: Perceptions of aging have been found to independently contribute to
      various aspects of health and wellbeing in old age. Since valid and reliable
      perceptions of aging instruments are unavailable in Dutch, these associations
      have not yet been tested in the Netherlands. This study examined the reliability
      and construct validity of the Dutch-language version of the 7-dimension Aging
      Perceptions Questionnaire (APQ). Furthermore, in order to decrease the response
      burden, while retaining the APQ's original factor structure, a short version of
      the APQ (APQ-S) was developed as an alternative to the 5-dimension Brief APQ (B
      APQ). METHODS: A Dutch translated version of the APQ was administered to a large
      sample of community-dwelling elders in the Netherlands, aged 70 to 99 (n = 1280),
      alongside measures of wellbeing and physical functioning. RESULTS: Confirmatory
      factor analyses confirmed the multidimensionality of the APQ. APQ scales were
      found to have good reliability and acceptable construct validity, yet several
      areas of localized strain were detected. These areas were addressed during item
      reduction, resulting in the 21-item APQ-S with an acceptable reliability and
      validity and a better overall model fit. While several notable differences were
      found, APQ-S results were largely comparable to that of the 5-dimension B-APQ.
      CONCLUSION: With its multidimensional nature and acceptable psychometric
      properties, the Dutch language version of the APQ may prove to be an invaluable
      instrument to assess the seven perceptions of aging dimensions among older
      populations for geriatric research. However, use of a shortened version is
      advised, as these are less labor intensive and areas of localized strain are
      addressed. The choice between the APQ-S and the B-APQ should be based on
      theoretical and practical considerations concerning the dimensional structure
      most suitable for the study.

PMID- 25963850
TI  - Discoid lupus erythematosus in a patient with myasthenia gravis.

PMID- 25963851
TI  - Toward the formation of a Companion Animal Parasite Council for the Tropics
      (CAPCT).
AB  - This letter advises the imminent formation of the Companion Animal Parasites
      Council for the Tropics (CAPCT). The CAPCT consists of region-specific (e.g.,
      Asia-Pacific, Latin America and Caribbean, Africa) experts comprising academics,
      veterinarians, parasitologists, physicians and allied industry partners that will
      work together to inform, guide and develop best-practice recommendations for the
      optimal diagnosis, treatment and control of companion animal parasites in the
      tropics, with the aim of protecting the health of pets and that of the public. 

PMID- 25963853
TI  - Survival in familial colorectal cancer: a Danish cohort study.
AB  - The monogenic Lynch syndrome (LS) is associated with better survival in
      colorectal cancer (CRC) patients. Whether family history of CRC affects CRC
      prognosis in general remains unclear. We evaluated overall mortality in a Danish
      cohort of CRC patients comparing patients with a family history (FHpos) to those
      without (FHneg) with focus on patients from non-syndromic families, thus FHpos
      patients were further divided into a non-syndromic group (FHNS) and a HNPCC/LS
      group (FHHNPCC). We included CRC patients diagnosed 1995-1998. First degree
      relatives were identified using Danish population registries and family history
      was obtained by linkage to Danish medical registries. 1- and 5-year mortality
      were evaluated using the Kaplan-Meier method and Cox regression, with adjustment
      for age, sex, cancer site, cancer stage, and comorbidity. 1196 CRC patients were
      included in the study, 219 FHpos patients of whom 197 were FHNS patients. 1- and
      5-year adjusted Mortality Rate Ratios comparing FHpos patients to FHneg patients
      were 0.99 (95% CI 0.69, 1.42) and 1.07 (95% CI 0.87, 1.32), respectively. For
      FHNS patients, the corresponding MRRs were 1.01 (95% CI 0.69, 1.47) and 1.15 (95%
      CI 0.93, 1.43). For the FHHNPCC patients MRRs were 0.84 (95% CI 0.29, 2.44) and
      0.66 (95% CI 0.33, 1.31), respectively. In contrast to the lower mortality in LS
      patients, other types of familial CRC do not seem to affect the survival after
      CRC diagnosis.

PMID- 25963854
TI  - Real-time investigation of human topoisomerase I reaction kinetics using an
      optical sensor: a fast method for drug screening and determination of active
      enzyme concentrations.
AB  - Human DNA topoisomerase I (hTopI) is a nuclear enzyme that catalyzes relaxation
      of super helical tension that arises in the genome during essential DNA metabolic
      processes. This is accomplished through a common reaction mechanism shared among
      the type IB topoisomerase enzymes, including eukaryotic and poxvirus
      topoisomerase I. The mechanism of hTopI is specifically targeted in cancer
      treatment using camptothecin derivatives. These drugs convert the hTopI activity
      into a cellular poison, and hence the cytotoxic effects of camptothecin
      derivatives correlate with the hTopI activity. Therefore, fast and reliable
      techniques for high throughput measurements of hTopI activity are of high
      clinical interest. Here we demonstrate potential applications of a fluorophore
      quencher based DNA sensor designed for measurement of hTopI cleavage-ligation
      activities, which are the catalytic steps affected by camptothecin. The kinetic
      analysis of the hTopI reaction with the DNA sensor exhibits a characteristic
      burst profile. This is the result of a two-step ping-pong reaction mechanism,
      where a fast first reaction, the one creating the signal, is followed by a slower
      second reaction necessary for completion of the catalytic cycle. Hence, the burst
      profile holds information about two reactions in the enzymatic mechanism.
      Moreover, it allows the amount of active enzyme in the reaction to be determined.
      The presented results pave the way for future high throughput drug screening and
      the potential of measuring active hTopI concentrations in clinical samples for
      individualized treatment. 

PMID- 25963852
TI  - Childhood cancers in families with and without Lynch syndrome.
AB  - Inheritance of a germline mutation in one of the DNA mismatch repair (MMR) genes
      or the EPCAM gene is associated with an increased risk of colorectal cancer,
      endometrial cancer, and other adult malignancies (Lynch syndrome). The risk of
      childhood cancers in Lynch syndrome families, however, is not well studied. Using
      data from the Colon Cancer Family Registry, we compared the proportion of
      childhood cancers (diagnosed before 18 years of age) in the first-, second-, and
      third-degree relatives of 781 probands with a pathogenic mutation in one of the
      MMR genes; MLH1 (n = 275), MSH2 (n = 342), MSH6 (n = 99), or PMS2 (n = 55) or in
      EPCAM (n = 10) (Lynch syndrome families), with that of 5073 probands with MMR
      deficient colorectal cancer (non-Lynch syndrome families). There was no evidence
      of a difference in the proportion of relatives with a childhood cancer between
      Lynch syndrome families (41/17,230; 0.24%) and non-Lynch syndrome families
      (179/94,302; 0.19%; p = 0.19). Incidence rate of all childhood cancers was
      estimated to be 147 (95% CI 107-206) per million population per year in Lynch
      syndrome families and 115 (95% CI 99.1-134) per million population per year in
      non-Lynch syndrome families. There was no evidence for a significant increase in
      the risk of all childhood cancers, hematologic cancers, brain and central nervous
      system cancers, Lynch syndrome-associated cancers, or other cancers in Lynch
      syndrome families compared with non-Lynch syndrome families. Larger studies,
      however, are required to more accurately define the risk of specific individual
      childhood cancers in Lynch syndrome families.

PMID- 25963855
TI  - Initial Efficacy of Hypofractionated Accelerated Chemo-Tomotherapy(r) for
      Nasopharyngeal Carcinoma.

PMID- 25963856
TI  - Long-term Results of a Survey of Prolonged Adjuvant Treatment with Temozolomide
      in Patients with Glioblastoma (SV3 Study).

PMID- 25963859
TI  - Caring for cancer patients with an intellectual disability: Attitudes and care
      perceptions of UK oncology nurses.
AB  - PURPOSE: Caring for people with cancer or an intellectual disability (ID) is
      stressful: little is known about the combined impact of caring for cancer
      patients with an ID, though this is expected to be especially challenging.
      METHOD: Eighty-three nurses, working in oncology or a related field (i.e.
      palliative care) were recruited. Perceptions of caring for patients with and
      without an ID were measured, alongside potentially confounding information about
      participant demographic characteristics and perceived stress. RESULTS:
      Participants felt less comfortable communicating with patients with an ID about
      their illness (F(1,82) = 59.52, p < 0.001), more reliant on a caregiver for
      communication (F(1,82) = 26.29, p < 0.001), and less confident that the patient's
      needs would be identified (F(1,82) = 42.03, p < 0.001) and met (F(1,81) = 62.90,
      p < 0.001). Participants also believed that caring for this patient group would
      induce more stress, compared with patients without an ID (F(1,81) = 31.592, p <
      0.001). Previous experience working with ID patient groups appears to mitigate
      some perceptions about providing care to this population. CONCLUSIONS: Caring for
      cancer patients with an ID may intensify this, already difficult, role. Through
      training and knowledge exchange, oncology nurse's confidence in communication,
      providing appropriate care, and positivity towards this patient group may be
      improved.

PMID- 25963860
TI  - The experience of distress in relation to surgical treatment and care for breast
      cancer: An interview study.
AB  - PURPOSE: A diagnosis of breast cancer is a key turning point in a woman's life
      that may lead to her experiencing severe and persistent distress and potentially
      presaging a psychiatric disorder, such as major depression. In Denmark an
      increased standardization of care and a short hospital stay policy minimize the
      time of medical and nursing surveillance. Consequently, there is the potential
      risk that distress goes unnoticed, and therefore, untreated. Therefore, the
      purpose of this study was to explore the experience of distress in Danish women
      taking part in surgical continuity of care for breast cancer. METHODS AND SAMPLE:
      A phenomenological-hermeneutic approach inspired by the French philosopher Paul
      Ricoeur was conducted to explore the experience of distress in relation to
      surgical treatment and care for breast cancer. Semi-structured interviews were
      conducted with 12 women who recently had surgery for breast cancer at six
      departments of breast surgery in Denmark from May 2013 to November 2013. KEY
      RESULTS: The understanding of the experience of distress in the period of
      surgical continuity of care for breast cancer is augmented and improved through a
      discussion related to four identified themes: A time of anxiety, loss of
      identities, being treated as a person and being part of a system, drawing on
      theory and other research findings. CONCLUSION: Distress experienced by women in
      the period following diagnosis arises from multiple sources. Support and care
      must be based on the woman's individual experience of distress.

PMID- 25963861
TI  - Gene expression in cell lines from propionic acidemia patients, carrier parents,
      and controls.
AB  - Propionic acidemia (PA) is an inborn of metabolism which usually presents with
      metabolic acidosis and accumulation of 3-hydroxypropionate among other toxins.
      Examining the gene expression in lymphoblastoid cell lines (LCLs) from PA
      patients, their carrier parents and age/sex-matched controls at normal glucose
      and low glucose growth conditions demonstrated differences among and between
      these groups. Using three-way ANOVA analysis, four DAVID clusters of response
      were identified of which three of the four clusters showed that LCLs from carrier
      parents had an intermediate response between healthy controls and PA patients.
      These differences included changes in expression of cell cycle regulatory genes,
      mitochondrial related genes, and transcriptional regulation. In addition,
      differences also were observed in expression of genes involved in
      transendothelial migration and focal adhesion at normal growth conditions when
      comparing the LCLs from PA patients and controls. These studies demonstrate
      transcriptional differences between LCLs from PA patients, their parents and
      biochemically normal controls. 

PMID- 25963862
TI  - Subgroups of US IRAQ and Afghanistan veterans: associations with traumatic brain
      injury and mental health conditions.
AB  - U. S. veterans of Iraq and Afghanistan are known to have a high prevalence of
      traumatic brain injury (TBI), posttraumatic stress disorder (PTSD), and
      depression, which are often comorbid and share many symptoms. Attempts to
      describe this cohort by single diagnoses have limited our understanding of the
      complex nature of this population. The objective of this study was to identify
      subgroups of Iraq and Afghanistan veterans (IAVs) with distinct compositions of
      symptoms associated with TBI, PTSD, and depression. Our cross-sectional,
      observational study included 303,716 IAVs who received care in the Veterans
      Health Administration in 2010-2011. Symptoms and conditions were defined using
      International Classification of Diseases, Ninth Revision codes and symptom
      clusters were identified using latent class analysis. We identified seven classes
      with distinct symptom compositions. One class had low probability of any
      condition and low health care utilization (HCU) (48 %). Other classes were
      characterized by high probabilities of mental health comorbidities (14 %);
      chronic pain and sleep disturbance (20 %); headaches and memory problems (6 %);
      and auditory problems (2.5 %). Another class had mental health comorbidities and
      chronic pain (7 %), and the last had high probabilities of most symptoms examined
      (3 %). These last two classes had the highest likelihood of TBI, PTSD, and
      depression and were identified as high healthcare utilizers. There are subgroups
      of IAVs with distinct clusters of symptom that are meaningfully associated with
      TBI, PTSD, depression, and HCU. Additional studies examining these veteran
      subgroups could improve our understanding of this complex comorbid patient
      population. 

PMID- 25963863
TI  - Polymorphisms in cytomegalovirus genotype in immunocompetent patients with
      corneal endotheliitis or iridocyclitis.
AB  - Cytomegalovirus (CMV) that caused corneal endotheliitis and iridocyclitis in
      immunocompetent patients was genotyped. The gB type1 was detected in seven
      endotheliitis samples (77.8%) and five iridocyclitis samples (100%), and the gB
      type 3 was detected in two endotheliitis samples (22.2%). The UL144 type 1 was
      found in five endotheliitis samples (45.5%) and five iridocyclitis samples
      (83.3%). The UL144 type 2 was found in two endotheliitis samples (18.2%) and one
      iridocyclitis sample (16.7%). The gB type 1 was predominant in endotheliitis and
      iridocyclitis, and the CMV genotypes in eyes with endotheliitis and iridocyclitis
      were similar.

PMID- 25963864
TI  - I may not be Southern by birth, but I am proud to be an American: The role of
      international medical graduates in vascular surgery and the Southern Association
      for Vascular Surgery.

PMID- 25963865
TI  - Discussion.

PMID- 25963867
TI  - Time, consensus and implementation: challenges for effective knowledge exchange.

PMID- 25963866
TI  - The value and economic analysis of routine postoperative carotid duplex
      ultrasound surveillance after carotid endarterectomy.
AB  - BACKGROUND: Several studies have reported on the role of postoperative duplex
      ultrasound surveillance after carotid endarterectomy (CEA) with varying results.
      Most of these studies had a small sample size or did not analyze cost
      effectiveness. METHODS: We analyzed 489 of 501 CEA patients with patch closure.
      All patients had immediate postoperative duplex ultrasound examination and were
      routinely followed up both clinically and with duplex ultrasound at regular
      intervals of 1 month, 6 months, 12 months, and every 12 months thereafter. A
      Kaplan-Meier analysis was used to estimate the rate of >=50% and >=80% post-CEA
      restenosis over time and the time frame of progression from normal to >=50% or
      >=80% restenosis. The cost of post-CEA duplex surveillance was also estimated.
      RESULTS: Overall, 489 patients with a mean age of 68.5 years were analyzed. Ten
      of these had residual postoperative >=50% stenosis, and 37 did not undergo a
      second duplex ultrasound examination and therefore were not included in the final
      analysis. The mean follow-up was 20.4 months (range, 1-63 months), with a mean
      number of duplex ultrasound examinations of 3.6 (range, 1-7). Eleven of 397
      patients (2.8%) with a normal finding on immediate postoperative duplex
      ultrasound vs 4 of 45 (8.9%) with mild stenosis on immediate postoperative duplex
      ultrasound progressed to >=50% restenosis (P = .055). Overall, 15 patients (3.1%)
      had >=50% restenosis, 9 with 50% to <80% and 4 with 80% to 99% (2 of these had
      carotid artery stenting reintervention), and 2 had late carotid occlusion. All of
      these were asymptomatic, except for one who had a transient ischemic attack. The
      mean time to >=50% to <80% restenosis was 14.7 months vs 19.8 months for >=80%
      restenosis after the CEA. Freedom from restenosis rates were 98%, 96%, 94%, 94%,
      and 94% for >=50% restenosis and 99%, 98%, 97%, 97%, and 97% for >=80% restenosis
      at 1 year, 2 years, 3 years, 4 years, and 5 years, respectively. Freedom from
      myocardial infarction, stroke, and deaths was not significantly different between
      patients with and without restenosis (100%, 93%, 83%, and 83% vs 94%, 91%, 86%,
      and 79% at 1 year, 2 years, 3 years, and 4 years, respectively; P = .951). The
      estimated charge of this surveillance was 3.6 * 489 (number of CEAs) * $800
      (charge for carotid duplex ultrasound), which equals $1,408,320, to detect only
      four patients with >=80% to 99% restenosis who may have been potential candidates
      for reintervention. CONCLUSIONS: This study shows that the value of routine
      postoperative duplex ultrasound surveillance after CEA with patch closure may be
      limited, particularly if the finding on immediate postoperative duplex ultrasound
      is normal or shows minimal disease.

PMID- 25963868
TI  - Response to commentaries.

PMID- 25963869
TI  - Global statistics on addictive behaviours: 2014 status report.
AB  - BACKGROUND AND AIMS: Addictive behaviours are among the greatest scourges on
      humankind. It is important to estimate the extent of the problem globally and in
      different geographical regions. Such estimates are available, but there is a need
      to collate and evaluate these to arrive at the best available synthetic figures.
      Addiction has commissioned this paper as the first of a series attempting to do
      this. METHODS: Online sources of global, regional and national information on
      prevalence and major harms relating to alcohol use, tobacco use, unsanctioned
      psychoactive drug use and gambling were identified through expert review and
      assessed. The primary data sources located were the websites of the World Health
      Organization (WHO), the United Nations Office on Drugs and Crime (UNODC) and the
      Alberta Gambling Research Institute. Summary statistics were compared with recent
      publications on the global epidemiology of addictive behaviours. RESULTS: An
      estimated 4.9% of the world's adult population (240 million people) suffer from
      alcohol use disorder (7.8% of men and 1.5% of women), with alcohol causing an
      estimated 257 disability-adjusted life years lost per 100 000 population. An
      estimated 22.5% of adults in the world (1 billion people) smoke tobacco products
      (32.0% of men and 7.0% of women). It is estimated that 11% of deaths in males and
      6% of deaths in females each year are due to tobacco. Of 'unsanctioned
      psychoactive drugs', cannabis is the most prevalent at 3.5% globally, with each
      of the others at < 1%; 0.3% of the world's adult population (15 million people)
      inject drugs. Use of unsanctioned psychoactive drugs accounts for an estimated 83
      disability-adjusted life years lost per 100 000 population. Global estimates of
      problem gambling are not possible, but in countries where it has been assessed
      the prevalence is estimated at 1.5%. CONCLUSIONS: Tobacco and alcohol use are by
      far the most prevalent addictive behaviours and cause the large majority of the
      harm. However, the quality of data on prevalence and addiction-related harms is
      mostly low, and comparisons between countries and regions must be viewed with
      caution. There is an urgent need to review the quality of data on which global
      estimates are made and coordinate efforts to arrive at a more consistent
      approach.

PMID- 25963870
TI  - Diagnosing an alcohol use disorder-what criteria should be used?

PMID- 25963871
TI  - Evidence of harm from late night alcohol sales continues to strengthen.

PMID- 25963872
TI  - The changing landscape of hepatitis C treatment-not 'can we cure?' but 'who
      should we cure first?' Is this an ethical approach?

PMID- 25963873
TI  - The Australian Treatment Outcome Study - implications for treatment philosophies,
      policy, political processes and practice.

PMID- 25963874
TI  - Coherent long-term treatment approaches-superior in the treatment of opioid
      dependence.

PMID- 25963875
TI  - The facts are clear.

PMID- 25963876
TI  - Ecological momentary assessment - new insights and opportunities.

PMID- 25963877
TI  - Ludek Kubicka, 1924-2014.

PMID- 25963880
TI  - Comparison between breast MRI and contrast-enhanced spectral mammography.
AB  - BACKGROUND: The main goal of this study was to compare contrast-enhanced spectral
      mammography (CESM) and breast magnetic resonance imaging (MRI) with
      histopathological results and to compare the sensitivity, accuracy, and positive
      and negative predictive values for both imaging modalities. MATERIAL/METHODS:
      After ethics approval, CESM and MRI examinations were performed in 102 patients
      who had suspicious lesions described in conventional mammography. All visible
      lesions were evaluated independently by 2 experienced radiologists using BI-RADS
      classifications (scale 1-5). Dimensions of lesions measured with each modality
      were compared to postoperative histopathology results. RESULTS: There were 102
      patients entered into CESM/MRI studies and 118 lesions were identified by the
      combination of CESM and breast MRI. Histopathology confirmed that 81 of 118
      lesions were malignant and 37 were benign. Of the 81 malignant lesions, 72 were
      invasive cancers and 9 were in situ cancers. Sensitivity was 100% with CESM and
      93% with breast MRI. Accuracy was 79% with CESM and 73% with breast MRI. ROC
      curve areas based on BI-RADS were 0.83 for CESM and 0.84 for breast MRI. Lesion
      size estimates on CESM and breast MRI were similar, both slightly larger than
      those from histopathology. CONCLUSIONS: Our results indicate that CESM has the
      potential to be a valuable diagnostic method that enables accurate detection of
      malignant breast lesions, has high negative predictive value, and a false
      positive rate similar to that of breast MRI.

PMID- 25963882
TI  - Systematic review on the use of omalizumab for the treatment of asthmatic
      children and adolescents.
AB  - BACKGROUND: There are less data on omalizumab treatment in pediatric asthma than
      in adult population. Thus, to establish the efficacy and safety of subcutaneous
      omalizumab as an add-on therapy, a systematic review of placebo-controlled
      studies was performed. METHODS: Primary outcome was the frequency of asthma
      exacerbations. Secondary outcomes included spirometric measures, rescue
      medication use, asthma symptoms, health-related quality of life, and adverse
      events. RESULTS: Three randomized controlled trials (1381 participants) fulfilled
      the selection criteria. During the stable phase, omalizumab decreased the number
      of patients with at least one significant asthma exacerbation (26.7% vs. 40.6%,
      NNTB = 7, 95% CI, 5, 11). The predefined post hoc subgroup analysis showed that
      duration of treatment did not influence this result. During the steroid reduction
      phase, omalizumab reduced the number of patients with at least one exacerbation
      (RR = 0.48, 95% CI, 0.38, 0.61; NNTB = 6, 95% CI, 4, 8) and also the mean number
      of asthma exacerbations per patient (MD = -0.44, 95% CI, -0.72, -0.17) when
      compared to placebo. The frequency of serious adverse events was similar between
      omalizumab (5.2%) and placebo (5.6%), and there were no evidence of increased
      risk of hypersensitivity reactions, nor malignant neoplasms. CONCLUSIONS: Data
      indicate that the efficacy of an add-on omalizumab in patients with moderate-to
      severe allergic asthma uncontrolled with recommended inhaled steroid treatment is
      accompanied by an acceptable safety profile.

PMID- 25963881
TI  - Perception of self: distinguishing autoimmunity from autoinflammation.
AB  - Rheumatic diseases can be divided in two groups, autoinflammatory and autoimmune
      disorders. The clinical presentation of both types of diseases overlap, but the
      pathological pathways underlying rheumatic autoinflammation and autoimmunity are
      distinct and are the subject of ongoing research. There are a number of ways in
      which these groups of diseases differ in terms of disease mechanisms and
      therapeutic responses. First, autoinflammatory diseases are driven by endogenous
      danger signals, metabolic mediators and cytokines, whereas autoimmunity involves
      the activation of T and B cells, the latter requiring V-(D)-J recombination of
      receptor-chain gene segments for maturation. Second, the efficacy of biologic
      agents directed against proinflammatory cytokines (for example IL-1beta and TNF)
      also highlights differences between autoinflammatory and autoimmune processes.
      Finally, whereas autoinflammatory diseases are mostly driven by inflammasome
      induced IL-1beta and IL-18 production, autoimmune diseases are associated with
      type I interferon (IFN) signatures in blood. In this Review, we provide an
      overview of the monocyte intracellular pathways that drive autoinflammation and
      autoimmunity. We convey recent findings on how the type I IFN pathway can
      modulate IL-1beta signalling (and vice versa), and discuss why IL-1beta-mediated
      autoinflammatory diseases do not perpetuate into autoimmunity. The origins of
      intracellular autoantigens in autoimmune disorders are also discussed. Finally,
      we suggest how new mechanistic knowledge of autoinflammatory and autoimmune
      diseases might help improve treatment strategies to benefit patient care. 

PMID- 25963883
TI  - Biocatalyzed approach for the surface functionalization of poly(L-lactic acid)
      films using hydrolytic enzymes.
AB  - Poly(lactic acid) as a biodegradable thermoplastic polyester has received
      increasing attention. This renewable polyester has found applications in a wide
      range of products such as food packaging, textiles and biomedical devices. Its
      major drawbacks are poor toughness, slow degradation rate and lack of reactive
      side-chain groups. An enzymatic process for the grafting of carboxylic acids onto
      the surface of poly(L-lactic acid) (PLLA) films was developed using Candida
      antarctica lipase B as a catalyst. Enzymatic hydrolysis of the PLLA film using
      Humicola insolens cutinase in order to increase the number of hydroxyl and
      carboxylic groups on the outer polymer chains for grafting was also assessed and
      showed a change of water contact angle from 74.6 to 33.1 degrees  while the
      roughness and waviness were an order of magnitude higher in comparison to the
      blank. Surface functionalization was demonstrated using two different techniques,
      (14) C-radiochemical analysis and X-ray photoelectron spectroscopy (XPS) using
      (14) C-butyric acid sodium salt and 4,4,4-trifluorobutyric acid as model
      molecules, respectively. XPS analysis showed that 4,4,4-trifluorobutyric acid was
      enzymatically coupled based on an increase of the fluor content from 0.19 to
      0.40%. The presented (14) C-radiochemical analyses are consistent with the XPS
      data indicating the potential of enzymatic functionalization in different
      reaction conditions. 

PMID- 25963884
TI  - First molecular identification of Entamoeba polecki in a piglet in Japan and
      implications for aggravation of ileitis by coinfection with Lawsonia
      intracellularis.
AB  - Parasitic Entamoeba spp. are found in many vertebrate species including humans,
      as well as many livestock including pigs. In pigs, three Entamoeba spp., E. suis,
      and E. polecki and E. histolytica as zoonotic species, have been identified, but
      their pathogenicity has not been fully characterized. Here, we report the
      bacteriological, virological, and histopathological examination of three piglets
      with chronic diarrhea. Two animals appeared to be additionally infected with
      Lawsonia intracellularis, which caused a characteristic proliferative ileitis. In
      the piglet infected with Entamoeba spp., the trophozoites (approximately 10-15
      MUm with one nucleus in their cytoplasm) invaded into the lamina propria and the
      disease was worsened by the formation of ulcers and pseudomembranes. Genetic
      analysis identified the parasite as E. polecki (99.5% identity). Although E.
      polecki in humans or animals might be less pathogenic in the case of a single
      infection, coinfections with other pathogens including L. intracellularis may
      increase the severity of the disease.

PMID- 25963885
TI  - The clinical predictors of aetiology and complications among 173 patients
      presenting to the Emergency Department with oesophageal food bolus impaction from
      2004-2014.
AB  - BACKGROUND: Oesophageal food bolus impaction (OFBI) is a common gastrointestinal
      emergency. AIM: To describe contemporary aetiologies of OFBI, and variables that
      may predict eosinophilic esophagitis (EoE) related OFBI as well as complications.
      METHODS: Patients presenting to the Emergency Department between 2004 and 2014
      with OFBI who underwent oesophagogastroduodenoscopy (EGD) were included. Clinical
      and endoscopic variables, as well as complications, were recorded. Aetiology of
      OFBI was determined by reviewing endoscopy reports. A diagnosis of EoE was
      confirmed via pathology (>15 eosinophils/high-powered field) at the index or
      follow-up EGD. Logistic regression was used to report associations of variables
      and complications. RESULTS: Of the 173 patients with OFBI, 139 (80%) had an
      aetiology recognised, the most frequent being EoE (27%, n = 47), Schatzki's ring
      (20%, n = 34) and oesophageal stricture (13%, n = 22). Six patients (3%) had
      oesophageal cancer. Patients with EoE-related OFBI tended to be younger (42 vs.
      69 years, P < 0.001), male (81% vs. 52%, P = 0.001), have a prior history of OFBI
      (45% vs. 18%, P = 0.001), and present during spring or summer (62% vs. 44%, P =
      0.04). Eighteen patients (10%) had a complication associated with OFBI, with 3
      (2%) perforations. On multivariate regression, patients with EoE-related OFBI
      were not more likely to have a complication (OR 1.07, P = 0.92), although hypoxia
      at presentation (OR 59.7, P = 0.006) was associated with complications.
      CONCLUSIONS: Eosinophilic esophagitis accounts for over a quarter of patients
      with oesophageal food bolus impaction. Overall complication rate was 10%, with a
      2% perforation rate. Clinical characteristics of patients with eosinophilic
      esophagitis differ from other patients with oesophageal food bolus impaction.

PMID- 25963886
TI  - Acute myeloid leukemia in the vascular niche.
AB  - The greatest challenge in treating acute myeloid leukemia (AML) is refractory
      disease. With approximately 60-80% of AML patients dying of relapsed disease,
      there is an urgent need to define and target mechanisms of drug resistance.
      Unfortunately, targeting cell-intrinsic resistance has failed to improve clinical
      outcomes in AML. Emerging data show that cell-extrinsic factors in the bone
      marrow microenvironment protect and support AML cells. The vascular niche, in
      particular, regulates AML cell survival and cell cycling by both paracrine
      secretion and adhesive contact with endothelial cells. Moreover, AML cells can
      functionally integrate within vascular endothelia, undergo quiescence, and resist
      cytotoxic chemotherapy. Together, these findings support the notion of blood
      vessels as sanctuary sites for AML. Therefore, vascular targeting agents may
      serve to remit AML. Several early phase clinical trials have tested anti
      angiogenic agents, leukemia mobilizing agents, and vascular disrupting agents in
      AML patients. In general, these agents can be safely administered to AML patients
      and cardiovascular side effects were reported. Response rates to vascular
      targeting agents in AML have been modest; however, a majority of vascular
      targeting trials in AML are monotherapy in design and indiscriminate in patient
      recruitment. When considering the chemosensitizing effects of targeting the
      microenvironment, there is a strong rationale to build upon these early phase
      clinical trials and initiate phase IB/II trials of combination therapy where
      vascular targeting agents are positioned as priming agents for cytotoxic
      chemotherapy.

PMID- 25963887
TI  - Conditioning solid tumor microenvironment through inflammatory chemokines and
      S100 family proteins.
AB  - Recently, there has been growing attention to the role of the tumor
      microenvironment (TME) in cancer growth, metastasis and emergence of chemotherapy
      resistance. Stromal and tumor cells make up the TME and interact with each other
      through a complex cross-talk manner. This interaction is facilitated by a variety
      of growth factors, cytokines, chemokines and S100 proteins. In this review, we
      focus on chemokines and their cognate receptors in regulating the tumorigenic
      process. Chemokines are cytokines that have chemotactic potential. Chemokine
      receptors are expressed on tumor cells and stromal cells. Chemokines and their
      cognate receptors modulate tumor growth and metastasis in a paracrine and
      autocrine manner. They play a major role in the modulation of stromal cell
      recruitment, angiogenic potential, cancer cell proliferation, survival, adhesion,
      invasion and metastasis to distant sites. In addition, a new class of calcium
      binding family S100 proteins has been getting attention as they play significant
      roles in tumor progression and metastasis by modulating TME. Here, we highlight
      recent developments regarding the inflammatory chemokine/S100 protein systems in
      the TME. We also focus on how chemokines/S100 proteins, through their role in the
      TME, modulate cancer cell ability to grow, proliferate, invade and metastasize to
      different organs. This review highlights the possibility of using the
      chemokine/chemokine receptor axis as a promising strategy in cancer therapy, the
      current difficulties in achieving this goal, and how it could be overcome for
      successful future therapeutic intervention. 

PMID- 25963888
TI  - David Barker, Buruli ulcer and the epidemiology of a neglected tropical disease.
AB  - In 1969, David Barker, his wife and four children moved to Uganda to work at
      Makerere Medical School in the capital Kampala. During the 1960s, Makerere had
      become a research and teaching centre with an international reputation based on
      the work of Trowell, Burkitt, Hutt and many others who had pioneered studies
      explaining the disease patterns in the West Nile area on the basis of the local
      climate, nutrition and lifestyle. David Barker was funded by the Medical Research
      Council to carry out research on a poorly understood disease, Buruli ulcer,
      joining Scottish surgeon Wilson Carswell, who was later to achieve fame as the
      role model for Dr Garrigan in Giles Foden's novel The Last King of Scotland. 

PMID- 25963890
TI  - Safety and tolerability of ledipasvir/sofosbuvir with and without ribavirin in
      patients with chronic hepatitis C virus genotype 1 infection: Analysis of phase
      III ION trials.
AB  - In phase III studies, treatment with the once-daily fixed-dose combination tablet
      of ledipasvir/sofosbuvir (LDV/SOF) with and without ribavirin (RBV) resulted in
      high rates of sustained virological response (SVR) in patients chronically
      infected with genotype 1 hepatitis C virus, including those with compensated
      cirrhosis. We conducted an analysis of data from these trials to compare the
      safety and tolerability profile of LDV-SOF with and without RBV. We analyzed
      treatment-emergent adverse events (AEs) and laboratory abnormalities in patients
      who were randomized to 8, 12, and 24 weeks of LDV/SOF with or without RBV. In
      total, data from 1,952 patients (of whom 872 received LDV/SOF with RBV and 1,080
      received LDV/SOF alone) were analyzed. Overall, 308 patients (16%) were African
      American, 224 (11%) had compensated cirrhosis, 501 (26%) had a body mass index
      >=30 kg/m(2) , and 440 (23%) were treatment experienced. Treatment-related AEs
      occurred in 71% and 45% of patients treated with and without RBV, respectively,
      including fatigue, insomnia, irritability, and rash/pruritus. Patients receiving
      RBV with LDV/SOF were more likely to require dose modification, interruptions of
      treatment resulting from AEs, or require the use of concomitant medications than
      those receiving LDV/SOF alone. Rates of treatment-related serious AEs and
      discontinuations resulting from AEs were similarly low (<1%) in both groups. The
      rate of SVR in those receiving RBV and those not receiving RBV was the same
      (97%). CONCLUSION: LDV/SOF plus RBV was associated with a greater incidence of
      AEs as well as concomitant medication use than LDV/SOF alone. Use of RBV did not
      impact the efficacy of LDV/SOF regimens in the ION phase III studies.

PMID- 25963891
TI  - Purification of high-quality RNA from synthetic polyethylene glycol-based
      hydrogels.
AB  - Polyethylene glycol (PEG)-based hydrogels, with variable stiffness, are widely
      used in tissue engineering to investigate substrate stiffness effects on cell
      properties. Transcriptome analysis is a critical method for understanding cell
      physiology. However, significant RNA degradation was observed during the process
      of isolating and purifying RNA from cells encapsulated in the PEG hydrogel,
      thereby precluding purification of high-quality RNA. Here, we describe a simple
      protocol that prevents RNA degradation and improves the quality and yield of RNA
      isolated from cells cultured in PEG hydrogels. This modification produces high
      quality total RNA suitable for RNA sequencing and microarray analysis. 

PMID- 25963892
TI  - Trimethine cyanine dyes as fluorescent probes for amyloid fibrils: The effect of
      N,N'-substituents.
AB  - The effect of various N,N'-substituents in the molecule of benzothiazole
      trimethine cyanine dye on its ability to sense the amyloid aggregates of protein
      was studied. The dyes are low fluorescent when free and in the presence of
      monomeric proteins, but their emission intensity sharply increases in complexes
      with aggregated insulin and lysozyme, with the fluorescence quantum yield
      reaching up to 0.42. The dyes carrying butyl, hydroxyalkyl, and phenylalkyl
      groups as N,N'-substituents possess the increased fluorescent sensitivity to
      fibrillar lysozyme, whereas the ones carrying quaternary amino groups are
      preferably sensitive to fibrillar insulin. This fluorescent sensitivity
      preference provided by the N,N'-functional groups could be explained by the
      interaction between these groups and protein side chains. The strongest
      fluorescent response (up to 70times) and the same sensitivity to aggregates of
      both proteins were exhibited by the dye D-51 carrying N-sulfoalkyl group. The
      studied cyanines allow the detection of fibrillar aggregates in the wide range up
      to 0.8 to 300MUg/ml and permit monitoring the protein aggregation kinetics with
      high reproducibility. The modification of trimethine cyanine dyes by functional
      substituents in N,N'-positions is suggested as a tool for the design of
      fluorescent molecules with the enhanced fluorescent sensitivity to the fibrillar
      aggregates of proteins. 

PMID- 25963893
TI  - CAP(+) selection: A combined chemical-enzymatic strategy for efficient eukaryotic
      messenger RNA enrichment via the 5' cap.
AB  - Eukaryotic messenger RNAs (mRNAs) are generally enriched using oligo(dT)
      selection. However, a significant fraction of mRNAs contain either short or no
      poly(A). Our technique permits the isolation of mRNAs via their unique
      biochemical feature, the 5' cap. It involves RNA extraction, blocking of the 3'
      ribose cis-diol by cordycepin, oxidation of the 5' cis-diol of the CAP to a
      dialdehyde, coupling to a biotinylated linker, and enrichment on a streptavidin
      affinity matrix. We demonstrate that it efficiently pulls out a synthetic capped
      and non-polyadenylated transcript used to spike total cell RNA as well as
      endogenous histone 3c mRNA reported to be poly(A) negative. 

PMID- 25963894
TI  - Simple and sensitive progesterone detection in human serum using a CdSe/ZnS
      quantum dot-based direct binding assay.
AB  - In this study, we developed a CdSe/ZnS quantum dot (QD)-based immunoassay for use
      in determining the presence of progesterone (P4) in human serum. Hydrophilic QDs
      were conjugated to anti-progesterone antibody (P4Ab) via ethyl-3
      (dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS) as
      coupling reagents. After purification, the P4Ab-QD conjugates were immobilized
      onto the wells of a 96-well microtiter plate, and a direct-binding immunoassay
      based on the binding of P4 to immobilized P4Ab-QD conjugates had a detection
      limit of 0.21 ng/ml and a sensitivity of 1.37 ng/ml, with a linear range of 0.385
      to 4.55 ng/ml. The proposed immunoassay was successfully used to determine the P4
      concentration in real human serum, and the results showed a good correlation with
      the accredited radioimmunoassay (RIA).

PMID- 25963895
TI  - Functional analysis of protein ubiquitination.
AB  - Alterations in the protein ubiquitination can lead to the development of serious
      pathological conditions and diseases and, therefore, are under extensive
      investigation. Here we detail the revised/updated version of two approaches for
      analyzing the functional activities of the ubiquitin transferring system and
      target protein ubiquitination. These approaches permit the analysis of protein
      ubiquitination within the cellular environment as well as in a tube when the
      purified components are used. The updates introduced in the protocols allow both
      to increase the sensitivity of the assays and to reduce the false positives often
      experienced in the analyses. 

PMID- 25963896
TI  - Magnetic beads-based electrochemical immunosensor for monitoring allergenic food
      proteins.
AB  - Screen-printed platinum electrodes as transducer and magnetic beads as solid
      phase were combined to develop a particle-based electrochemical immunosensor for
      monitoring the serious food allergen ovalbumin. The standard arrangement of
      enzyme-linked immunosorbent assay became the basis for designing the
      immunosensor. A sandwich-type immunocomplex was formed between magnetic particles
      functionalized with specific anti-ovalbumin immunoglobulin G and captured
      ovalbumin molecules, and secondary anti-ovalbumin antibodies conjugated with the
      enzyme horseradish peroxidase were subsequently added as label tag. The
      electrochemical signal proportional to the enzymatic reaction of horseradish
      peroxidase during the reduction of hydrogen peroxide with thionine as electron
      mediator was measured by linear sweep voltammetry. The newly established method
      of ovalbumin detection exhibits high sensitivity suitable for quantification in
      the range of 11 to 222nM and a detection limit of 5nM. Magnetic beads-based assay
      format using external magnets for rapid and simple separation has been proven to
      be an excellent basis for electrochemical detection and quantification of food
      allergens in highly complex sample matrices. 

PMID- 25963897
TI  - Heterospecific SNP diversity in humans and rhesus macaque (Macaca mulatta).
AB  - BACKGROUND: Conservation of single nucleotide polymorphisms (SNPs) between human
      and other primates (i.e., heterospecific SNPs) in candidate genes can be used to
      assess the utility of those organisms as models for human biomedical research.
      METHODS: A total of 59,691 heterospecific SNPs in 22 rhesus macaques and 20
      humans were analyzed for human trait associations and 4207 heterospecific SNPs
      biallelic in both taxa were compared for genetic variation. RESULTS: Variation
      comparisons at the 4207 SNPs showed that humans were more genetically diverse
      than rhesus macaques with observed and expected heterozygosities of 0.337 and
      0.323 vs. 0.119 and 0.102, and minor allele frequencies of 0.239 and 0.063,
      respectively. In total, 431 of the 59,691 heterospecific SNPs are reportedly
      associated with human-specific traits. CONCLUSION: While comparisons between
      human and rhesus macaque genomes are plausible, functional studies of
      heterospecific SNPs are necessary to determine whether rhesus macaque alleles are
      associated with the same phenotypes as their corresponding human alleles.

PMID- 25963898
TI  - Addressing Low Colorectal Cancer Screening in African Americans: Using Focus
      Groups to Inform the Development of Effective Interventions.
AB  - African Americans have the highest burden of colorectal cancer (CRC) in the
      United States of America (USA) yet lower CRC screening rates than whites.
      Although poor screening has prompted efforts to increase screening uptake, there
      is a persistent need to develop public health interventions in partnership with
      the African American community. The aim of this study was to conduct focus groups
      with African Americans to determine preferences for the content and mode of
      dissemination of culturally tailored CRC screening interventions. In June 2013,
      45-75-year-old African Americans were recruited through online advertisements and
      from an urban Veterans Affairs system to create four focus groups. A semi
      structured interview script employing open-ended elicitation was used, and
      transcripts were analyzed using ATLAS.ti software to code and group data into a
      concept network. A total of 38 participants (mean age = 54) were enrolled, and 59
      ATLAS.ti codes were generated. Commonly reported barriers to screening included
      perceived invasiveness of colonoscopy, fear of pain, and financial concerns.
      Facilitators included poor diet/health and desire to prevent CRC. Common sources
      of health information included media and medical providers. CRC screening
      information was commonly obtained from medical personnel or media. Participants
      suggested dissemination of CRC screening education through commercials,
      billboards, influential African American public figures, Internet, and radio.
      Participants suggested future interventions include culturally specific
      information, including details about increased risk, accessing care, and
      dispelling of myths. Public health interventions to improve CRC screening among
      African Americans should employ media outlets, emphasize increased risk among
      African Americans, and address race-specific barriers. Specific recommendations
      are presented for developing future interventions.

PMID- 25963899
TI  - Immunohistochemical detection of IgM and IgG in lung tissue of dogs with
      leptospiral pulmonary haemorrhage syndrome (LPHS).
AB  - Leptospiral pulmonary haemorrhage syndrome (LPHS) is a severe form of
      leptospirosis. Pathogenic mechanisms are poorly understood. Lung tissues from 26
      dogs with LPHS, 5 dogs with pulmonary haemorrhage due to other causes and 6
      healthy lungs were labelled for IgG (n=26), IgM (n=25) and leptospiral antigens
      (n=26). Three general staining patterns for IgG/IgM were observed in lungs of
      dogs with LPHS with most tissues showing more than one staining pattern: (1)
      alveolar septal wall staining, (2) staining favouring alveolar surfaces and (3)
      staining of intra-alveolar fluid. Healthy control lung showed no staining,
      whereas haemorrhagic lung from dogs not infected with Leptospira showed staining
      of intra-alveolar fluid and occasionally alveolar septa. Leptospiral antigens
      were not detected. We conclude that deposition of IgG/IgM is demonstrable in the
      majority of canine lungs with naturally occurring LPHS, similar to what has been
      described in other species. Our findings suggest involvement of the host humoral
      immunity in the pathogenesis of LPHS and provide further evidence to support the
      dog as a natural disease model for human LPHS. 

PMID- 25963900
TI  - The Story of EHS-GREPA 1979-2014.

PMID- 25963902
TI  - Retraction: Novel self-inactivating vectors for reconstitution of wiskott-Aldrich
      syndrome.
AB  - This article has been withdrawn at the request of the authors. The Publisher
      apologizes for any inconvenience this may have caused. 

PMID- 25963903
TI  - Targeting of miR9/NOTCH1 interaction reduces metastatic behavior in triple
      negative breast cancer.
AB  - Many reports have indicated deregulation of a variety of microRNAs (miRNAs) in
      human cancers. In this study, we appraised miR-9 correlation with NOTCH1 involved
      in Notch signaling in metastatic breast cancer. The Notch signaling pathway has
      been approved to be associated with the development and progression of many human
      cancers, including breast cancer, but the precise mechanism has remained unknown.
      To the best of our knowledge, this is the first study that introduces miR-9 and
      NOTCH1 correlation as an effective factor in breast cancer. We found that miR-9
      expression was decreased in MDA-MB-231 breast cancer cells compared with MCF-10A
      normal breast cell line. However, NOTCH1 was upregulated in the metastatic breast
      cancer cells. Furthermore, luciferase assay revealed a significant inverse
      correlation between miR-9 and NOTCH1. Overexpression of Notch signaling via
      Notch1 intracellular domain in MDA-MB-231 cell line was suppressed by
      lentiviruses expressing miR-9. Taken together, the results obtained by MTT, flow
      cytometry, migration, and wound healing assays showed that it is possible to
      inhibit metastasis and induce pro-apoptotic state by induction of miR-9
      expression in MDA-MB-231 cells but with no effect on cell proliferation. These
      results shows that miR-9, by direct targeting of NOTCH1, can reveal a suppressor
      like activity in metastatic breast cancer cells. 

PMID- 25963901
TI  - Deletion of Galphaq in the telencephalon alters specific neurobehavioral
      outcomes.
AB  - G(alphaq) -coupled receptors are ubiquitously expressed throughout the brain and
      body, and it has been shown that these receptors and associated signaling
      cascades are involved in a number of functional outputs, including motor function
      and learning and memory. Genetic alterations to G(alphaq) have been implicated in
      neurodevelopmental disorders such as Sturge-Weber syndrome. Some of these
      associated disease outcomes have been modeled in laboratory animals, but as
      G(alphaq) is expressed in all cell types, it is difficult to differentiate the
      underlying circuitry or causative neuronal population. To begin to address
      neuronal cell type diversity in G(alphaq) function, we utilized a conditional
      knockout mouse whereby G(alphaq) was eliminated from telencephalic glutamatergic
      neurons. Unlike the global G(alphaq) knockout mouse, we found that these
      conditional knockout mice were not physically different from control mice, nor
      did they exhibit any gross motor abnormalities. However, similarly to the
      constitutive knockout animal, G(alphaq) conditional knockout mice demonstrated
      apparent deficits in spatial working memory. Loss of G(alphaq) from glutamatergic
      neurons also produced enhanced sensitivity to cocaine-induced locomotion,
      suggesting that cortical G(alphaq) signaling may limit behavioral responses to
      psychostimulants. Screening for a variety of markers of forebrain neuronal
      architecture revealed no obvious differences in the conditional knockouts,
      suggesting that the loss of G(alphaq) in telencephalic excitatory neurons does
      not result in major alterations in brain structure or neuronal differentiation.
      Taken together, our results define specific modulation of spatial working memory
      and psychostimulant responses through disruptions in G(alphaq) signaling within
      cerebral cortical glutamatergic neurons.

PMID- 25963904
TI  - The Current Drug Treatment Landscape for Diabetes and Perspectives for the
      Future.
AB  - The escalating global epidemic of type 2 diabetes mellitus has focused attention
      on the devastating consequences of protracted hyperglycemia. Early and effective
      intervention to control blood glucose is a fundamental principle of treatment
      guidelines, requiring assiduous use of current therapies. However, many patients
      do not achieve or maintain glycemic targets, emphasizing the need for further
      therapies. This narrative review assesses the available medicinal options to
      address hyperglycemia and the opportunities to develop novel agents. 

PMID- 25963905
TI  - Epithelioid Hemangioendothelioma of the Maxillary Sinus.
AB  - The clinical course and pathologic features of a 72 year old female who presented
      with epistaxis are presented. Radiographic findings were notable for a large,
      soft tissue lesion filling the maxillary sinus with significant bony erosion and
      expansion. The patient was ultimately diagnosed with epithelioid
      hemangioendothelioma (EHE) and underwent endoscopic resection. She has no
      evidence of local, regional or distant recurrence 14 months post-surgery. The
      rarity of this neoplasm, the unusual anatomic location and non-specific symptoms
      present diagnostic and management challenges. Epithelioid vascular tumors
      encompass a spectrum of benign and malignant tumors. EHE itself is thought to
      have an intermediate malignant behavior pattern, though cases with indolent
      behavior have been reported. Differentiation of EHE from other lesions has
      historically based on histopathology. Additionally, recent studies have described
      a recurrent genetic fusion WWTR1-CAMTA1 in EHE, involving t(1;3) (p36;q25). This
      represents the second reported case of EHE arising in a paranasal sinus. The
      histopathologic findings of this lesion are reviewed.

PMID- 25963906
TI  - The need for further integration of services to prevent mother-to-child
      transmission of HIV and syphilis in Mwanza City, Tanzania.
AB  - OBJECTIVE: To assess the operational integration of maternal HIV testing and
      syphilis screening in Mwanza, Tanzania. METHODS: Interviews were conducted with
      76 health workers (HW) from three antenatal clinics (ANC) and three maternity
      wards in 2008-2009 and 1137 consecutive women admitted for delivery. Nine ANC
      health education sessions and client flow observations were observed. RESULTS:
      Only 25.0% of HWs reported they had received training in both prevention of
      mother-to-child transmission (PMTCT) and syphilis screening. HIV and syphilis
      tests were sometimes performed in different rooms and results recorded in
      separate registers with different formats and the results were not always given
      by the same person. At delivery, most women had been tested for both HIV (79.4%)
      and syphilis (88.1%) during pregnancy. Of those not tested antenatally for each
      infection, 70.1% were tested for HIV at delivery but none for syphilis.
      CONCLUSION: Integration of maternal HIV and syphilis screening was limited.
      Integrated care guidelines and related health worker training should address this
      gap.

PMID- 25963907
TI  - The cost-effectiveness of 10 antenatal syphilis screening and treatment
      approaches in Peru, Tanzania, and Zambia.
AB  - OBJECTIVE: Rapid plasma reagin (RPR) is frequently used to test women for
      maternal syphilis. Rapid syphilis immunochromatographic strip tests detecting
      only Treponema pallidum antibodies (single RSTs) or both treponemal and non
      treponemal antibodies (dual RSTs) are now available. This study assessed the cost
      effectiveness of algorithms using these tests to screen pregnant women. METHODS:
      Observed costs of maternal syphilis screening and treatment using clinic-based
      RPR and single RSTs in 20 clinics across Peru, Tanzania, and Zambia were used to
      model the cost-effectiveness of algorithms using combinations of RPR, single, and
      dual RSTs, and no and mass treatment. Sensitivity analyses determined drivers of
      key results. RESULTS: Although this analysis found screening using RPR to be
      relatively cheap, most (>70%) true cases went untreated. Algorithms using single
      RSTs were the most cost-effective in all observed settings, followed by dual
      RSTs, which became the most cost-effective if dual RST costs were halved. Single
      test algorithms dominated most sequential testing algorithms, although sequential
      algorithms reduced overtreatment. Mass treatment was relatively cheap and
      effective in the absence of screening supplies, though treated many uninfected
      women. CONCLUSION: This analysis highlights the advantages of introducing RSTs in
      three diverse settings. The results should be applicable to other similar
      settings.

PMID- 25963908
TI  - Elimination of mother-to-child transmission of HIV and syphilis: A dual approach
      in the African Region to improve quality of antenatal care and integrated disease
      control.
AB  - The World Health Organization's (WHO) Strategic Framework for the Elimination of
      New HIV Infections among Children in Africa by 2015 identifies important
      synergies for the elimination of mother-to-child transmission of HIV and syphilis
      in terms of prevention interventions, implementation logistics and service
      delivery, monitoring and evaluation systems, and need for sustained political
      commitment. The WHO advocates the use of an integrated, rights-based dual
      approach with partnerships and collaboration to make the best use of available
      resources. Through a consultative approach, six countries in the African Region
      committed to dual elimination and developed and implemented action plans for this
      purpose. Where interest and commitment are high, this may also be possible and
      effective in other African countries. 

PMID- 25963909
TI  - Improving global estimates of syphilis in pregnancy by diagnostic test type: A
      systematic review and meta-analysis.
AB  - BACKGROUND: "Probable active syphilis," is defined as seroreactivity in both non
      treponemal and treponemal tests. A correction factor of 65%, namely the
      proportion of pregnant women reactive in one syphilis test type that were likely
      reactive in the second, was applied to reported syphilis seropositivity data
      reported to WHO for global estimates of syphilis during pregnancy. OBJECTIVES: To
      identify more accurate correction factors based on test type reported. SEARCH
      STRATEGY: Medline search using: "Syphilis [Mesh] and Pregnancy [Mesh]," "Syphilis
      [Mesh] and Prenatal Diagnosis [Mesh]," and "Syphilis [Mesh] and Antenatal
      [Keyword]. SELECTION CRITERIA: Eligible studies must have reported results for
      pregnant or puerperal women for both non-treponemal and treponemal serology. DATA
      COLLECTION AND ANALYSIS: We manually calculated the crude percent estimates of
      subjects with both reactive treponemal and reactive non-treponemal tests among
      subjects with reactive treponemal and among subjects with reactive non-treponemal
      tests. We summarized the percent estimates using random effects models. MAIN
      RESULTS: Countries reporting both reactive non-treponemal and reactive treponemal
      testing required no correction factor. Countries reporting non-treponemal testing
      or treponemal testing alone required a correction factor of 52.2% and 53.6%,
      respectively. Countries not reporting test type required a correction factor of
      68.6%. CONCLUSIONS: Future estimates should adjust reported maternal syphilis
      seropositivity by test type to ensure accuracy.

PMID- 25963911
TI  - Radiolabeling of [18F]-fluoroethylnormemantine and initial in vivo evaluation of
      this innovative PET tracer for imaging the PCP sites of NMDA receptors.
AB  - INTRODUCTION: The N-methyl-D-aspartate receptor (NMDAr) is an ionotropic receptor
      that mediates excitatory transmission. NMDAr overexcitation is thought to be
      involved in neurological and neuropsychiatric disorders such as Alzheimer disease
      and schizophrenia. We synthesized [(18)F]-fluoroethylnormemantine ([(18)F]-FNM),
      a memantine derivative that binds to phencyclidine (PCP) sites within the NMDA
      channel pore. These sites are primarily accessible when the channel is in the
      active and open state. METHODS: Radiosynthesis was carried out using the
      Raytest(r) SynChrom R&D fluorination module. Affinity of this new compound was
      determined by competition assay. We ran a kinetic study in rats and computed a
      time-activity curve based on a volume-of-interest analysis, using CARIMAS(r)
      software. We performed an ex vivo autoradiography, exposing frozen rat brain
      sections to a phosphorscreen. Adjacent sections were used to detect NMDAr by
      immunohistochemistry with an anti-NR1 antibody. As a control of the specificity
      of our compound for NMDAr, we used a rat anesthetized with ketamine. Correlation
      analysis was performed with ImageJ software between signal of autoradiography and
      immunostaining. RESULTS: Fluorination yield was 10.5% (end of synthesis), with a
      mean activity of 3145 MBq and a specific activity above 355 GBq/MUmol. Affinity
      assessment allowed us to determine [(19)F]-FNM IC50 at 6.1 10(-6)M. [(18)F]-FMN
      concentration gradually increased in the brain, stabilizing at 40 minutes post
      injection. The brain-to-blood ratio was 6, and 0.4% of the injected dose was
      found in the brain. Combined ex vivo autoradiography and immunohistochemical
      staining demonstrated colocalization of NMDAr and [(18)F]-FNM (r=0.622,
      p<0.0001). The highest intensity was found in the cortex and cerebellum, and the
      lowest in white matter. A low and homogeneous signal corresponding to unspecific
      binding was observed when PCP sites were blocked with ketamine. CONCLUSIONS:
      [(18)F]-FNM appears to be a promising tracer for imaging NMDAr activity for
      undertaking preclinical studies in perspective of clinical detection of
      neurological or neuropsychological disorders.

PMID- 25963912
TI  - Effects of Maternal and Fetal Characteristics on Cell-Free Fetal DNA Fraction in
      Maternal Plasma.
AB  - OBJECTIVE: To study factors that influence the concentration of cell-free fetal
      DNA (fetal fraction) using a large clinical data set of pregnancies with male
      fetus. METHOD: A retrospective analysis of 23 067 pregnancies that received
      noninvasive prenatal testing from January 2012 to October 2013, including 22 650
      normal singleton pregnancies (control group) and 417 pregnancies with aneuploidy,
      twin pregnancy, or various maternal conditions including preexisting
      hypertension, preexisting diabetes, hyperthyroidism, and carrier of the surface
      antigen of the hepatitis B virus (HBsAg; study group). Multiples of the median
      (MoM) analysis was performed in the control group to derive gestation and body
      mass index (BMI)-corrected fetal fraction. The effects of study group conditions
      on fetal fraction were examined by calculating the ratio of MoM (RMoM) values.
      RESULTS: Fetal fraction showed a positive correlation with gestational age (r(2)
      = .10, P < .001) and increased rapidly after the 21 weeks of gestation (r(2) =
      .26, P < .001). Negative association with maternal BMI was found with fetal
      fraction (r(2) = .04, P < .001). In study group, fetal fraction was higher among
      pregnant women with a trisomy 21 fetus (RMoM = 1.24, P < .001) and lower among
      trisomy 18 (RMoM = 0.84, P < .001). A 1.6-fold incensement of fetal fraction was
      observed in twin fetuses comparing to singleton pregnancy (RMoM = 1.62, P <
      .001). Women with preexisting hypertension had significantly lower fetal fraction
      (RMoM = 0.85, P = .02). Preexisting diabetes, hyperthyroidism, or carrier of
      HBsAg did not affect fetal fraction. CONCLUSION: The fetal fraction was affected
      by fetal aneuploidy, maternal BMI, and the number of gestation. Maternal
      preexisting of hypertension appeared to reduce fetal fraction.

PMID- 25963913
TI  - Expression of Interferon gamma by Decidual Cells and Natural Killer Cells at the
      Human Implantation Site: Implications for Preeclampsia, Spontaneous Abortion, and
      Intrauterine Growth Restriction.
AB  - Human first-trimester decidual cells (FTDCs) chemoattract CXCR3-expressing
      circulating CD56(bright)CD16(-) natural killer (NK) cells, which increase
      uteroplacental blood flow by remodeling spiral arteries and arterioles. This
      recruitment reflects elevated FTDC expression of NK cell-recruiting induced
      protein 10 and interferon (IFN)-inducible T-cell-alpha chemoattractant produced
      in response to the synergistic effects of tumor necrosis factor alpha (TNF-alpha)
      and IFN-gamma stimulation. Decidual macrophages express TNF-alpha, whereas the
      cellular origin of IFN-gamma is unclear. Therefore, this study aims to identify
      the cell source(s) of IFN-gamma in human first trimester decidua. Immunostaining
      of decidual sections revealed that both FTDCs and decidual NK (dNK) cells express
      IFN-gamma. Although individual dNK cells express higher IFN-gamma levels, the
      more numerous FTDCs account for greater proportion of total IFN-gamma
      immunostaining. Freshly isolated FTDCs express greater IFN-gamma staining than
      dNK cells as measured by flow cytometry, whereas incubation of dNK cells with
      documented NK cell activators significantly increases IFN-gamma above FTDC
      levels. Confluent FTDCs intrinsically produce, but paradoxically respond to,
      exogenous IFN-gamma. 

PMID- 25963915
TI  - Effects of Pazopanib, Sunitinib, and Sorafenib, Anti-VEGF Agents, on the Growth
      of Experimental Endometriosis in Rats.
AB  - We aimed to compare the effects of pazopanib, sunitinib, and sorafenib on
      endometriotic tissue morphology and histological characteristics as well as
      ovarian reserve in a rat model. Experimental endometriosis was established in 32
      rats. They were randomly divided into 4 groups (8 rats for each group) to
      administer study drugs: pazopanib, sunitinib, sorafenib, and normal saline.
      Histological examination with hematoxylin and eosin staining to determine
      endometriosis score and immunostaining with primary vascular endothelial growth
      factor (VEGF), CD117, and Bax antibodies were performed. Bilateral ovaries
      excised to determine the ovarian follicle number. The endometriosis score was
      significantly reduced by pazopanib compared to other study drugs and by sunitinib
      compared to sorafenib and normal saline (P < .05). Sorafenib did not affect
      endometriosis score (P > .05). The VEGF score was significantly decreased
      similarly by pazopanib, sunitinib, and sorafenib compared to normal saline (P <
      .05). The CD117 score was reduced by pazopanib and sunitinib similarly compared
      to both sorafenib and normal saline that provided similar effect on the score (P
      < .05). The Bax scores of all the groups were found similar (P > .05). No study
      drugs caused meaningful change in the ovarian follicle number (P > .05).
      Pazopanib reduces the growth of endometriotic implants. This effect may be
      related to the suppressive effect of pazopanib on the endometriotic tissue
      expressions of VEGF and CD117 but not Bax. The study drugs do not affect ovarian
      reserve. The inconsistent effects of study drugs regarding study parameters
      require further studies to elucidate the molecular bases of their effects on the
      growth of endometriotic implants. 

PMID- 25963914
TI  - Dysregulation of Lysyl Oxidase Expression in Lesions and Endometrium of Women
      With Endometriosis.
AB  - Lysyl oxidases (LOXs) are enzymes involved in collagen deposition, extracellular
      membrane remodeling, and invasive/metastatic potential. Previous studies reveal
      an association of LOXs and endometriosis. We aimed to identify the mechanisms
      activated by upregulation of lysyl oxidases (LOX) in endometriotic cells and
      tissues. We hypothesized that LOX plays a role in endometriosis by promoting
      invasiveness and epithelial to mesenchymal transition (EMT). METHODS: The LOX
      protein expression levels were measured by immunohistochemistry in lesions and
      endometrium on a tissue microarray (TMA) and in endometrial biopsies from
      patients and controls during the window of implantation (WOI). Estradiol
      regulation of LOX expression was determined by quantitative polymerase chain
      reaction (qPCR). Proliferation, invasion, and migration assays were performed in
      epithelial (endometrial epithelial cell), endometrial (human endometrial stromal
      cell), and endometriotic cell lines (ECL and 12Z). Pathway-focused multiplex qPCR
      was used to determine transcriptome changes due to LOX overexpression. RESULTS:
      LOX protein was differentially expressed in ovarian versus peritoneal lesions.
      During WOI, LOX levels were higher in luminal epithelium of patients with
      endometriosis-associated infertility compared to controls. Invasive epithelial
      cell lines expressed higher levels of LOX than noninvasive ones. Transfection of
      LOX into noninvasive epithelial cells increased their migration in an LOX
      inhibitor-sensitive manner. Overexpression of LOX did not fully induce EMT but
      the expression of genes related to fibrosis and extracellular matrix remodeling
      were dysregulated. CONCLUSIONS: This study documents that expression of LOX is
      differentially regulated in endometriotic lesions and endometrium. A role for LOX
      in mediating proliferation, migration, and invasion of endometrial and
      endometriotic cells was observed, which may be implicated in the establishment
      and progression of endometriotic lesions.

PMID- 25963916
TI  - Binding of Anticell Adhesive Oxime-Crosslinked PEG Hydrogels to Cardiac Tissues.
AB  - Postsurgical cardiac adhesions increase the number of surgeries as well as
      patient mortality and morbidity. A fast gelling oxime-crosslinked PEG hydrogel
      with tunable gelation time, degradation, and mechanical properties is presented.
      This material is cytocompatible and prevents cellular adhesion. Material
      retention on different cardiac tissues is demonstrated ex vivo over time and that
      functional group ratio alters material retention on different cardiac tissues. 

PMID- 25963917
TI  - Midterm clinical outcome following Edwards SAPIEN or Medtronic Corevalve
      transcatheter aortic valve implantation (TAVI): Results of the Belgian TAVI
      registry.
AB  - OBJECTIVE: To assess midterm (3 years) clinical outcomes of transcatheter aortic
      valve implantation (TAVI) in Belgium using the Edwards SAPIEN valve or the
      Medtronic CoreValve transcatheter heart valve (THV). BACKGROUND: Medium and long
      term follow-up data of both THVs are still relatively scarce, although of great
      clinical relevance for a relatively new but rapidly expanding treatment modality.
      Therefore, reporting mid- and long term clinical outcome data, coming from large
      "real world" national registries, remains contributive. METHODS: Between December
      2007 and March 2012, 861 "real world" patients who were not candidates for
      surgical aortic valve replacement as decided by the local heart teams, underwent
      TAVI at 23 sites. Eleven sites exclusively used SAPIEN THV (n = 460), while 12
      exclusively used CoreValve THV (n = 401). Differences in clinical outcomes by
      valve system were assessed, according to access route and baseline EuroSCORE risk
      profile (<10%: low, 10-20%: intermediate and >20%: high risk). RESULTS: Overall
      cumulative survival at 3 years was 51% for SAPIEN vs. 60% for CoreValve (P =
      0.021). In transfemorally treated patients, SAPIEN and CoreValve had similar
      survival at 3 years for each of the baseline EuroSCORE cohorts (low risk: 72% vs.
      76%, P = 0.45; intermediate risk: 62% vs. 59%, P = 0.94; high risk: 48% vs. 53%,
      P = 0.65). CONCLUSION: Cumulative midterm 3 year survival after transfemoral TAVI
      in "real world" patients refused for surgery with similar baseline EuroSCORE risk
      profile is not different between SAPIEN or CoreValve.

PMID- 25963918
TI  - Alemtuzumab Pharmacokinetics in Hematopoietic Stem Cell Transplants for
      Nonmalignant Genetic Diseases.

PMID- 25963919
TI  - Serum Krebs Von Den Lungen-6 as a Biomarker for Early Detection of Bronchiolitis
      Obliterans Syndrome in Children Undergoing Allogeneic Stem Cell Transplantation.
AB  - Bronchiolitis obliterans syndrome (BOS) is a devastating complication after
      allogeneic stem cell transplantation (allo-SCT). Early identification of high
      risk patients is pivotal for success. Lung proteins, KL-6, CCSP, SP-A, and SP-D,
      measured in the serum may identify high-risk patients for BOS earlier than
      pulmonary function tests (PFTs) can identify changes or clinical symptoms. Lung
      proteins were measured in patients' serum at baseline and at 1, 3, 6, 9, 12, 18,
      and 24 months after transplantation along with history, clinical examination, and
      PFTs. Serum levels of lung proteins were also measured in healthy control
      subjects. The primary endpoint was the development of BOS confirmed by
      pathological biopsy or National Institutes of Health criteria. Between September
      2009 and September 2011, 39 patients were enrolled. Six children developed BOS at
      a median time of 200 days (range, 94 to 282). KL-6 levels were low in control
      subjects, at a median of .1 U/mL (range, .1 to 1.5). Pre-SCT and 1-month KL-6
      levels were significantly higher in surviving patients who developed BOS (n = 6)
      versus those who did not (n = 18) (pre-SCT: mean, 32.6 U/mL [IQR, 9.7 to 89.3]
      versus 5.8 U/mL [IQR, 2.1 to 12.6], P = .03; at 1 month: mean, 52.5 U/mL [IQR,
      20.2 to 121.3] versus 11.4 U/mL [IQR, 5.7 to 36.0], P = .04). Three- and 6-month
      KL-6 levels continued to be higher in BOS group but were not statistically
      significant. CCSP, SP-A, and SP-D were not predictive. KL-6 measured in the serum
      of children receiving allo-SCT may identify patients at high risk for the
      development of BOS. These patients will benefit from intensive surveillance
      protocol and early therapy before irreversible lung damage.

PMID- 25963920
TI  - Clinical Outcomes and Prognostic Factors of Up-Front Autologous Stem Cell
      Transplantation in Patients with Extranodal Natural Killer/T Cell Lymphoma.
AB  - Limited data exist on up-front autologous stem cell transplantation (ASCT) in
      extranodal natural killer/T cell lymphoma (ENKTL). Sixty-two patients (43 men and
      19 women) with newly diagnosed ENKTL who underwent up-front ASCT after primary
      therapy were identified. Poor-risk characteristics included advanced stage (50%),
      high-intermediate to high-risk International Prognostic Index (25.8%), and group
      3 to 4 of NK/T Cell Lymphoma Prognostic Index (NKPI, 67.7%). Pretransplant
      responses included complete remission in 61.3% and partial remission in 38.7% of
      patients, and final post-transplantation response included complete remission in
      78.3%. Early progression occurred in 12.9%. At a median follow-up of 43.3 months
      (range, 3.7 to 114.6), 3-year progression-free survival (PFS) was 52.4% and 3
      year overall survival (OS) was 60.0%. Patients with limited disease had
      significantly better 3-year PFS (64.5% versus 40.1%, P = .017) and OS (67.6%
      versus 52.3%, P = .048) than those with advanced disease. Multivariate analysis
      showed NKPI and pretransplant response were independent prognostic factors
      influencing survival, particularly NKPI in limited disease and pretransplant
      response in advanced disease. Radiotherapy was an independent factor for reduced
      progression and survival in patients with limited disease, but anthracycline
      based chemotherapy was a poor prognostic factor for progression in patients with
      advanced disease. Up-front ASCT is an active treatment in ENKTL patients
      responding to primary therapy.

PMID- 25963921
TI  - Functional Myeloid-Derived Suppressor Cell Subsets Recover Rapidly after
      Allogeneic Hematopoietic Stem/Progenitor Cell Transplantation.
AB  - Myeloid-derived suppressor cells (MDSCs) are regulatory cell populations that
      have the ability to suppress effector T cell responses and promote the
      development of regulatory T cells (Tregs). They are a heterogeneous population of
      immature myeloid progenitors that include monocytic and granulocytic subsets. We
      postulated that given the rapid expansion of myeloid cells post-transplant, these
      members of the innate immune system may be important contributors to the early
      immune environment post-transplant. To evaluate the kinetics of recovery and
      function of MDSCs after allogeneic hematopoietic stem cell transplant (HSCT), 26
      patients undergoing allogeneic HSCT were studied at 6 time points in the first 3
      months after HSCT. Both MDSC subsets recovered between 2 and 4 weeks, well before
      the recovery of T and B lymphocytes. MDSC subset recovery positively correlated
      with T, B, and/or double-negative T cell numbers after HSCT. MDSCs isolated from
      patients post-transplant were functional in that they suppressed third-party
      CD4(+) T cell proliferation and Th1 differentiation and promoted Treg
      development. In conclusion, functional MDSC are present early after HSCT and
      likely contribute to the regulatory cell population post-transplant. 

PMID- 25963922
TI  - MiR-125a targets effector programs to stabilize Treg-mediated immune homeostasis.
AB  - Although different autoimmune diseases show discrete clinical features, there are
      common molecular pathways intimately involved. Here we show that miR-125a is
      downregulated in peripheral CD4(+) T cells of human autoimmune diseases including
      systemic lupus erythematosus and Crohn's disease, and relevant autoimmune mouse
      models. miR-125a stabilizes both the commitment and immunoregulatory capacity of
      Treg cells. In miR-125a-deficient mice, the balance appears to shift from immune
      suppression to inflammation, and results in more severe pathogenesis of colitis
      and experimental autoimmune encephalomyelitis (EAE). The genome-wide target
      analysis reveals that miR-125a suppresses several effector T-cell factors
      including Stat3, Ifng and Il13. Using a chemically synthesized miR-125a analogue,
      we show potential to re-programme the immune homeostasis in EAE models. These
      findings point to miR-125a as a critical factor that controls autoimmune diseases
      by stabilizing Treg-mediated immune homeostasis. 

PMID- 25963923
TI  - Chemical Proteomics Uncovers EPHA2 as a Mechanism of Acquired Resistance to Small
      Molecule EGFR Kinase Inhibition.
AB  - Tyrosine kinase inhibitors (TKIs) have become an important therapeutic option for
      treating several forms of cancer. Gefitinib, an inhibitor of the epidermal growth
      factor receptor (EGFR), is in clinical use for treating non-small cell lung
      cancer (NSCLC) harboring activating EGFR mutations. However, despite high initial
      response rates, many patients develop resistance to gefitinib. The molecular
      mechanisms of TKI resistance often remain unclear. Here, we describe a chemical
      proteomic approach comprising kinase affinity purification (kinobeads) and
      quantitative mass spectrometry for the identification of kinase inhibitor
      resistance mechanisms in cancer cells. We identified the previously described
      amplification of MET and found EPHA2 to be more than 10-fold overexpressed (p <
      0.001) in gefitinib-resistant HCC827 cells suggesting a potential role in
      developing resistance. siRNA-mediated EPHA2 knock-down or treating cells with the
      multikinase inhibitor dasatinib restored sensitivity to gefitinib. Of all
      dasatinib targets, EPHA2 exhibited the most drastic effect (p < 0.001). In
      addition, EPHA2 knockdown or ephrin-A1 treatment of resistant cells decreased FAK
      phosphorylation and cell migration. These findings confirm EPHA2 as an actionable
      drug target, provide a rational basis for drug combination approaches, and
      indicate that chemical proteomics is broadly applicable for the discovery of
      kinase inhibitor resistance. 

PMID- 25963924
TI  - Survival outcomes of secondary cancers in patients with Waldenstrom
      macroglobulinemia: An analysis of the SEER database.
AB  - We hypothesized that survival outcomes of WM patients who develop SM is distinct
      from the general population of individuals who develop those same malignancies.
      Using the SEER-18 data (2000-2011), we identified patients with cancers of the
      breast, prostate, lung, colorectum, bladder, melanoma, non-Hodgkin lymphoma
      (NHL), and acute leukemia, and compared their outcomes according to having
      antecedent WM or not. The outcome of interest was overall survival (OS), which
      was analyzed in proportional-hazard models adjusted for age, sex, race, and
      stage. We found that patients with WM who developed SM were older than population
      controls with those same cancers. In the multivariate analysis, WM cases with
      colorectal cancer (HR 1.97; P < 0.001), melanoma (HR 2.63; P < 0.001) and NHL (HR
      = 1.35; P = 0.02) had worse OS than controls with those respective cancers. WM
      patients with diffuse large B-cell lymphoma also had worse OS (HR = 1.86; P =
      0.008). The utilization of surgery and radiation was similar between WM cases and
      controls, except lower rates of prostatectomy and melanoma surgery among WM
      patients. The survival of WM patients with colorectal cancer, melanoma, and NHL
      is worse than among general population controls, arguing in favor of age
      appropriate cancer screening.

PMID- 25963925
TI  - Effects of Buerger Exercise Combined Health-Promoting Program on Peripheral
      Neurovasculopathy Among Community Residents at High Risk for Diabetic Foot
      Ulceration.
AB  - BACKGROUND: Peripheral neuropathy and vasculopathy are important risk factors for
      diabetic foot ulceration (DFU). Buerger exercises for patients with arterial
      occlusive disease have previously been noted; however, current evidence to
      support this intervention is limited. AIM: We established a standardized
      procedure for Buerger exercises combined with a health-promoting program and
      investigated its effectiveness in reducing peripheral neurovasculopathy among
      rural Taiwanese residents with type 2 diabetes who were at high risk of
      developing DFU. METHODS: A one group quasi-experimental pretest-posttest design
      was used. The Buerger exercise protocol composed of a three-step posture change
      with 9 minutes for each cycle. The health-promoting program composed of six
      dimensions of healthy habits. Outcome measurements 1 year after the beginning of
      the intervention included the ankle brachial pressure index (ABI), the Michigan
      neuropathy screening instrument (MNSI), blood pressure, frequency of self
      reported leg discomfort, and a type 2 Diabetes Health Promoting Score. FINDINGS:
      Thirty-one of 66 (47%) subjects completed this study. Buerger exercises combined
      with the health-promoting program significantly improved (a) the ABI in the legs,
      (b) health-promoting behaviors, (c) MNSI values, and (d) leg discomfort symptoms.
      LINKING EVIDENCE TO ACTION: This study supports the use of Buerger exercises
      combined with the health-promoting program to improve symptoms of peripheral
      neuropathy and peripheral circulation in patients with type 2 diabetes.

PMID- 25963926
TI  - Assessment of family history of substance abuse for preventive interventions with
      patients experiencing chronic pain: A quality improvement project.
AB  - This quality improvement project demonstrates that RN Care Managers, in a chronic
      pain programme, can assess for a family history of substance abuse in 5-10 min.
      Information informs treatment based on specific high risk criteria. Benefits
      include heightened awareness of the genetic and environmental risks associated
      with a family history of substance abuse, an opportunity to participate in
      motivational interventions to prevent or minimize consequences of substance use
      disorders, and likely substantial overall health-care cost savings. 

PMID- 25963927
TI  - Probing the dynamics of growth factor receptor by single-molecule fluorescence
      imaging.
AB  - Single-molecule fluorescence imaging with living cells offers a new approach to
      visualize and monitor individual proteins during their cellular activities. It
      facilities the study of cell signaling proteins whose structures and interactions
      are highly temporal and spatial regulated. In this review, we will mainly present
      our recent work on probing the dynamics of two types of important transmembrane
      growth factor receptors, transforming growth factor beta receptors and epidermal
      growth factor receptors, by single-molecule fluorescence microscopy. This
      includes the characterization of receptor stoichiometry, monomer-dimer
      interconversion kinetics, effects of microenvironment on receptor membrane
      diffusion, and intracellular transportation under different signaling conditions.
      Related studies on these receptors from other groups, as well as the method
      developments, will be also discussed. Single-molecule study helps to achieve a
      better understanding of the molecular mechanism of receptor activation,
      endocytosis and other molecular events in transmembrane signaling. 

PMID- 25963928
TI  - Magnitude of muscle wasting early after on-pump coronary artery bypass graft
      surgery and exploration of aetiology.
AB  - NEW FINDINGS: What is the central question of this study? It remains uncertain
      whether significant fat-free mass wasting occurs early after coronary artery
      bypass graft surgery, and the aetiology of this wasting in these particular
      conditions is unexplored. What is the main finding and its importance?
      Significant fat-free mass wasting is present after coronary artery bypass graft
      surgery, and this wasting effect is greater in younger patients and in patients
      with greater increments in blood cortisol-to-testosterone ratios after surgery.
      The magnitude and aetiology of muscle wasting early after coronary artery bypass
      graft (CABG) surgery remains unknown. In the present study, we assessed changes
      in fat-free mass early after CABG surgery and explored the possible aetiology
      (relationships with postsurgical changes in blood hormones, insulin resistance,
      subject characteristics and inflammation) for these changes. Fat-free mass was
      assessed before and 23 (range: 25) days after CABG surgery in 25 subjects. Blood
      testosterone, cortisol, insulin-like growth factor-1, growth hormone, sex hormone
      binding globulin, glucose, insulin, C-peptide and C-reactive protein
      concentrations were determined, and free androgen index, cortisol-to-testosterone
      ratio and HOMA-IR index were all calculated before surgery, during the first 3
      days after surgery and at reassessment of body composition. Relationships between
      changes in fat-free mass and changes in blood parameters after surgery or subject
      characteristics were studied. After surgery, free androgen index and blood sex
      hormone-binding globulin, testosterone and insulin-like growth factor-1
      concentrations decreased significantly, while HOMA-IR index, cortisol-to
      testosterone ratio, blood growth hormone, insulin and C-reactive protein
      concentrations increased significantly (P < 0.0025, observed alpha > 0.80). Whole
      body fat-free mass decreased significantly [by -1.9 (range: 9.1) kg, P < 0.0025,
      observed alpha = 0.99] after surgery. According to regression analysis, greater
      absolute loss of fat-free mass was observed after CABG surgery in subjects who
      were younger, who experienced a greater increase in blood cortisol-to
      testosterone ratio after surgery and/or who underwent earlier reassessment of
      body composition (P < 0.05). Significant decrements in fat-free mass were
      observed early after CABG surgery, especially in younger subjects and/or subjects
      with elevated blood cortisol-to-testosterone ratios after surgery. Interventions
      to preserve fat-free mass soon after CABG surgery are thus warranted.

PMID- 25963929
TI  - Acquisition of new tumor cell properties by MSC-derived exosomes.
AB  - Interaction between multi-functional mesenchymal stroma/stem cells (MSC) and
      human tumor cells involves the exchange of biological material via extracellular
      vesicles including exosomes. Protein analysis of MSC-derived exosomes
      demonstrated the presence of MMP-2 and MSC-specific markers including CD90 and
      ecto-5'-nucleotidase (CD73). Incubation of tumor cells with these membranous
      particles revealed a rapid uptake of MSC-released microvesicles whereby breast
      cancer cells incorporated ~19% and SCCOHT-1 cells representing a rare type of
      small cell ovarian cancer assimilated ~28% of available exosomes within 24 h.
      This interaction was accompanied by functional alterations of tumor cell
      properties during integration of exosomal content from MSC. Indeed, exosome
      associated MMP-2 exhibited functional enzyme activity and MCF-7 breast cancer
      cells with undetectable MMP-2 protein acquired expression of this enzyme and
      corresponding gelatinase functionality after stimulation with MSC-derived
      exosomes. Similar effects were observed in SCCOHT-1 cells during culture in the
      presence of MSC-derived exosomes which enabled new metabolic activities in this
      tumor cell type. Together, these findings demonstrated that the internalization
      of MSC-derived exosomes was associated with the acquisition of new tumor cell
      properties by altering cellular functionalities and providing the capability to
      re-organize the tumor microenvironment.

PMID- 25963930
TI  - Methane emission, digestive characteristics and faecal archaeol in heifers fed
      diets based on silage from brown midrib maize as compared to conventional maize.
AB  - The aim of the present experiment was to compare silage prepared from maize
      having a brown midrib (BMR) mutation with control (CTR) maize to identify their
      effects on enteric methane emission, digesta mean retention time (MRT), ruminal
      fermentation and digestibility. In addition, the utility of archaeol present in
      faecal samples was validated as a proxy for methane production. Seven German
      Holstein heifers were fed total mixed rations with a maize-silage proportion
      (either BMR or CTR) of 920 g/kg dry matter (DM) in a change-over design. Heifers
      were fed boluses with markers to measure MRT; faeces were collected for 7 days
      and rumen fluid was collected on the penultimate day. Methane emission was
      measured in respiration chambers on one day. Data were analysed by t-test and
      regression analysis. DM intake did not differ between the two diets. The apparent
      digestibility of DM and most nutrients was unaffected by diet type, but apparent
      digestibility of neutral and acid detergent-fibre was higher in those heifers fed
      BMR than in those fed CTR. Comparisons between diets revealed no difference in
      particle or solute MRT in the gastro-intestinal tract and the reticulorumen.
      Concentrations of short-chain fatty acid and ammonia in rumen fluid and its pH
      were not affected by silage type. Independent of the mode of expression [l/d,
      l/kg DM intake, l/kg digested organic matter], methane emissions were not
      affected by maize-silage type, but with BMR, there was a trend towards lower
      methane production per unit of digested neutral detergent fibre than there was
      with CTR silage. Results of the present study show that feeding heifers BMR
      silage does not increase methane emissions despite a higher fibre digestibility
      as compared to CTR silage. Therefore, it is assumed that improvements in animal
      productivity achieved by feeding BMR silage, as some studies have reported, can
      be obtained without extra environmental cost per unit of milk or meat. Neither
      faecal archaeol content [ug/g] nor daily amount excreted [mg/d] is suitable to
      predict methane production in absolute terms [l per day]. However, faecal
      archaeol content has a certain potential for predicting the methane yield [l per
      kg DM intake] of individual animals.

PMID- 25963931
TI  - Polymeric Micelle-Mediated Delivery of DNA-Targeting Organometallic Complexes for
      Resistant Ovarian Cancer Treatment.
AB  - Three half-sandwich iridium and ruthenium organometallic complexes with high
      cytotoxicity are synthesized, and their anticancer mechanisms are elucidated. The
      organometallic complexes can interact with DNA through coordination or
      intercalation, thereby inducing apoptosis and inhibiting proliferation of
      resistant cancer cells. The organometallic complexes are then incorporated into
      polymeric micelles through the polymer-metal coordination between poly(ethylene
      glycol)-b-poly(glutamic acid) [PEG-b-P(Glu)] and organometallic complexes to
      further enhance their anticancer effects as a result of the enhanced permeability
      and retention effect. The micelles with particle sizes of ~60 nm are more
      efficiently internalized by cancer cells than the corresponding complexes, and
      selectively dissociate and release organometallic anticancer agents within late
      endosomes and lysosomes, thereby enhancing drug delivery to the nuclei of cancer
      cells and facilitating their interactions with DNA. Thus, the micelles display
      higher antitumor activity than the organometallic complexes alone with a lack of
      the systemic toxicity in a mouse xenograft model of cisplatin-resistant human
      ovarian cancer. These results suggest that the polymeric micelles carrying
      anticancer organometallic complexes provide a promising platform for the
      treatment of resistant ovarian cancer and other hard-to-treat solid tumors. 

PMID- 25963933
TI  - [Hyponatremia and tolvaptan : what is the situation 5 years after approval?].
AB  - The diuretic tolvaptan has been approved for more than 5 years for the
      indications of euvolemic hyponatremia due to syndrome of inappropriate
      antidiuretic hormone (SIADH) secretion. In recent years many patients have been
      treated with tolvaptan and many physicians could gather practical experience.
      Other countries, such as the USA had already gained greater experience, also in
      the indications for hypervolemic hyponatremia. After approval was granted more
      than 5000 patients worldwide were included in the so-called hyponatremia register
      and 22 active centers in Germany with 317 patients participated. Although some
      details from this now concluded register have been published, the final
      publication of the multinational post-authorization safety study on tolvaptan in
      the treatment of SIADH has not yet been published. In the years 2012 and 2013 two
      warning letters were issued on tolvaptan. The first letter warned of the risk of
      a faster increase in serum sodium using tolvaptan and provided detailed
      information on how the risk of osmotic demeyelination can be minimized. So far
      only one proven case of osmotic demelination syndrome (ODS) is known; however,
      this occurred following incorrect use of tolvaptan in a monotherapy. The second
      warning letter provided information on the potential risk (reversible) of liver
      damage by tolvaptan, which resulted from the TEMPO 3:4 study. In this study
      tolvaptan was used in a higher dosage for therapy of autosomal dominant
      polycystic kidney disease. Although the European renal best practice (ERBP)
      guidelines from 2014 did not recommend tolvaptan for the indications of SIADH,
      other guidelines came to different conclusions. In summary, 5 years after the
      approval of tolvaptan there is still no consensus. At the current time many
      questions still remain unanswered. Initiation of therapy with tolvaptan remains
      reserved for experienced physicians in hospitals. Treatment must be adapted on
      the basis of a clinical estimation of the individual situation of each patient.

PMID- 25963932
TI  - Transcutaneous Vagus Nerve Stimulation Modulates Default Mode Network in Major
      Depressive Disorder.
AB  - BACKGROUND: Depression is the most common form of mental disorder in community
      and health care settings and current treatments are far from satisfactory. Vagus
      nerve stimulation (VNS) is a Food and Drug Administration approved somatic
      treatment for treatment-resistant depression. However, the involvement of surgery
      has limited VNS only to patients who have failed to respond to multiple treatment
      options. Transcutaneous VNS (tVNS) is a relatively new, noninvasive VNS method
      based on the rationale that there is afferent/efferent vagus nerve distribution
      on the surface of the ear. The safe and low-cost characteristics of tVNS have the
      potential to significantly expand the clinical application of VNS. METHODS: In
      this study, we investigated how tVNS can modulate the default mode network (DMN)
      functional connectivity (FC) in mild or moderate major depressive disorder (MDD)
      patients. Forty-nine MDD patients were recruited and received tVNS or sham tVNS
      (stVNS) treatments. RESULTS: Thirty-four patients completed the study and were
      included in data analysis. After 1 month of tVNS treatment, the 24-item Hamilton
      Depression Rating Scale score reduced significantly in the tVNS group as compared
      with the stVNS group. The FC between the DMN and anterior insula and
      parahippocampus decreased; the FC between the DMN and precuneus and orbital
      prefrontal cortex increased compared with stVNS. All these FC increases are also
      associated with 24-item Hamilton Depression Rating Scale reduction. CONCLUSIONS:
      tVNS can significantly modulate the DMN FC of MDD patients; our results provide
      insights to elucidate the brain mechanism of tVNS treatment for MDD patients.

PMID- 25963934
TI  - A systematic review of acute kidney injury in pediatric allogeneic hematopoietic
      stem cell recipients.
AB  - The process of allogeneic HSCT in children is associated with frequent AKI and
      mortality, but the epidemiology is not widely reported. The aim of this review
      was to summarize the available evidence on incidence, risk factors, timing, and
      prognosis of AKI in children following HSCT. We systematically reviewed all
      observational studies reporting incidence and outcomes of AKI in pediatric
      allogenic HSCT recipients. The minimum criteria for AKI were defined as an
      increase in sCr >= x1.5 or urine output <=0.5 mL/kg/min over six h. Medline and
      Embase were searched until March 2014. From 993 electronic records, five were
      eligible for inclusion (n = 571 patients). The average incidence of AKI within
      the first 100 days following HSCT was 21.7% (range 11-42%), and the average time
      of onset was 4-6 wk post-transplant. Risk factors for AKI included cyclosporine
      toxicity, amphotericin B and foscarnet, SOS, and having a mismatched donor. There
      were conflicting reports on whether AKI was associated with the development of
      CKD. AKI is a common and potentially life-threatening complication following HSCT
      in children. Further quality observational studies are needed to accurately
      determine the epidemiology and prognosis of AKI in this population.

PMID- 25963935
TI  - Development and validation of a generic stability-indicating MEEKC method for
      five fluoroquinolone antibiotics.
AB  - In this paper, a reliable stability-indicating generic MEEKC method for the
      analysis of five commonly used fluoroquinolones (FQs) has been developed and
      optimized by a central composite circumscribed experimental design. The
      separation was carried out using a fused silica capillary (60.2 cm total length)
      and a microemulsion (ME) composed of 81.75% (w/w) of a 125 mM NaH2 PO4 solution
      having a pH of 2.75, 2.65% (w/w) SDS, 1.00% (w/w) n-octanol, 6.60% (w/w) n
      butanol and 8.00% (w/w) 2-propanol. A voltage of 28 kV was applied in a reverse
      polarity mode. A linear relationship was established from 0.04 to 0.48 mg/ml with
      R2 values higher than 0.98 for all five FQs. Both repeatability and intermediate
      precision were less than 3% and accuracy ranging from 97 to 100%. Of note,
      ciprofloxacin impurity A and ofloxacin impurity A could be separated from the
      respective drug substance in a single run which cannot be achieved using the
      official HPLC method from the European Pharmacopoeia. Forced degradation of all
      FQs under heat, in acidic and alkaline medium, in the presence of oxidizing
      agents and under neutral hydrolysis conditions was investigated. The highest
      yield of degradation products was observed using oxidative hydrogen peroxide.
      Hence, the proposed MEEKC method can be used for the quantitative determination
      of the five FQs and their potential impurities within a total runtime of 20 min.

PMID- 25963937
TI  - ERRATUM: Chapter 3: One-Step Purification of Phosphinothricin Acetyltransferase
      Using Reactive Dye-Affinity Chromatography.

PMID- 25963936
TI  - Insights from Micro-second Atomistic Simulations of Melittin in Thin Lipid
      Bilayers.
AB  - The membrane disruption and pore-forming mechanism of melittin has been widely
      explored by experiments and computational studies. However, the precise mechanism
      is still enigmatic, and further study is required to turn antimicrobial peptides
      into future promising drugs against microbes. In this study, unbiased microsecond
      (us) time scale (total 17 us) atomistic molecular dynamics simulation were
      performed on multiple melittin systems in 1,2-dimyristoyl-sn-glycero-3
      phosphocholine membrane to capture the various events during the membrane
      disorder produced by melittin. We observed bent U-shaped conformations of
      melittin, penetrated deeply into the membrane in all simulations, and a special
      double U-shaped structure. However, no peptide transmembrane insertion, nor pore
      formation was seen, indicating that these processes occur on much longer
      timescales, and suggesting that many prior computational studies of melittin were
      not sufficiently unbiased. 

PMID- 25963938
TI  - Influence of Spanish TV commercials on child obesity.
AB  - OBJECTIVES: To examine the strategies used in food advertising campaigns on
      Spanish television and their breach of the Self-Regulation Code on Food
      Advertising aimed at Preventing Obesity and Promoting Healthy Habits in Children,
      as such breach advocates the consumption of products that fail to meet the
      nutritional requirements. STUDY DESIGN: Observational descriptive study. METHODS:
      Viewing and content analysis of 52 food commercials on the children's television
      channels 'Disney Channel' and 'Boing' on Saturday and Sunday (9:00-12:00) and
      general channels 'Telecinco' and 'Antena 3' on Monday to Friday (8:00-9:00 and
      17:00-20:00), from March to May 2013; subsequent analysis of the nutrition
      labelling of the advertised products. RESULTS: There are different ways of
      bypassing the advertising agreement. Strategies are used which hide or distort
      the facts about the product in favour of the advertiser. 18 advertisements refer
      to website or Facebook pages, thus facilitating feedback, and 11 advertisements
      refer to the Plan for Promoting Healthy Lifestyles in the Spanish Population.
      With regard to nutritional quality, the composition of the products analysed is
      high in sugars and saturated fats with average levels of fat and salt. A
      comparison of the broadcast time of the commercials shows that the figures for
      fat and saturated fat are similar in food advertised in the morning and in the
      afternoon, but products that are high in sugar and salt are advertised more in
      the morning. If the overall figures are compared, they are higher in foods
      advertised in the morning. DISCUSSION: The Self-Regulation Code is insufficient.
      There is an obvious risk of trivialising the messages of the health promotion
      plan. The regulation of advertising is complex and if the nutritional composition
      of the foods advertised is likely to lead to child obesity, it is essential to
      reflect on the consequences deriving from the advertising of these products.

PMID- 25963939
TI  - Sphaerisporangium corydalis sp. nov., isolated from the root of Corydalis
      yanhusuo L.
AB  - Two Gram-stain positive, aerobic actinomycete strains, designated NEAU-YHS12 and
      NEAU-YHS15(T), were isolated from the root of Corydalis yanhusuo L. collected
      from Wuchang, Heilongjiang Province, northeast China. Phylogenetic analysis of
      16S rRNA gene sequences showed that the two strains are closely related to one
      another (99.8 % similarity), and had the closest relationship with
      Sphaerisporangium cinnabarinum JCM 3291(T) (98.7, 98.6 %), Sphaerisporangium
      flaviroseum YIM 48771(T) (98.6, 98.6 %), Sphaerisporangium melleum JCM 13064(T)
      (98.5, 98.4 %) and Sphaerisporangium dianthi NEAU-CY18(T) (98.4, 98.4 %). DNA-DNA
      hybridization value between strains NEAU-YHS12 and NEAU-YHS15(T) was 82 +/- 1.4
      %, and the values between the two strains and the closely related type strains
      were well below 70 %. The two strains also shared a number of phenotypic
      characteristics that were distinct from the closely related species. Both strains
      were observed to contain MK-9(H6), MK-9(H4) and MK-9(H2) as the detected
      menaquinones. The cell wall peptidoglycan was found to contain meso
      diaminopimelic acid. The phospholipid profiles were found to contain
      diphosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylethanolamine,
      phosphatidylinositol, phosphatidylinositol mannoside, phosphoglycolipid, and an
      unidentified phospholipid. The major fatty acids were identified as iso-C16:0,
      C17:1 omega7c, C18:0 and iso-C15:0. On the basis of the genetic and phenotypic
      properties, it is proposed that strains NEAU-YHS15(T) and NEAU-YHS12 be
      classified as representatives of a novel species of the genus Sphaerisporangium,
      for which the name Sphaerisporangium corydalis sp. nov is proposed. The type
      strain is NEAU-YHS15(T) (CGMCC 4.7148(T) = DSM46732(T)).

PMID- 25963940
TI  - Factitious lobular panniculitis presenting as recurrent breast ulcers.

PMID- 25963942
TI  - Sulphated glycosaminoglycans and proteoglycans in the developing vertebral column
      of juvenile Atlantic salmon (Salmo salar).
AB  - In the present study, the distribution of sulphated glycosaminoglycans (GAGs) in
      the developing vertebral column of Atlantic salmon (Salmo salar) at 700, 900,
      1100 and 1400 d degrees  was examined by light microscopy. The mineralization
      pattern was outlined by Alizarin red S and soft structures by Alcian blue. The
      temporal and spatial distribution patterns of different types of GAGs:
      chondroitin-4-sulphate/dermatan sulphate, chondroitin-6-sulphate, chondroitin-0
      sulphate and keratan sulphate were addressed by immunohistochemistry using
      monoclonal antibodies against the different GAGs. The specific pattern obtained
      with the different antibodies suggests a unique role of the different GAG types
      in pattern formation and mineralization. In addition, the distribution of the
      different GAG types in normal and malformed vertebral columns from 15 g salmon
      was compared. A changed expression pattern of GAGs was found in the malformed
      vertebrae, indicating the involvement of these molecules during the pathogenesis.
      The molecular size of proteoglycans (PGs) in the vertebrae carrying GAGs was
      analysed with western blotting, and mRNA transcription of the PGs aggrecan,
      decorin, biglycan, fibromodulin and lumican by real-time qPCR. Our study reveals
      the importance of GAGs in development of vertebral column also in Atlantic salmon
      and indicates that a more comprehensive approach is necessary to completely
      understand the processes involved. 

PMID- 25963943
TI  - Identification, characterization and functional analysis of anti-apoptotic
      protein BCL-2-like gene from pufferfish, Takifugu obscurus, responding to
      bacterial challenge.
AB  - Apoptosis plays a crucial role in many biological processes, including
      development, cellular homeostasis and immune responses. The BCL-2 family is a key
      regulator of the mitochondrial response to apoptotic signals in the intrinsic
      pathway. In this study, we identified and characterized the cDNA and expression
      pattern of pufferfish BCL-2 (PfBCL-2). The full-length cDNA of PfBCL-2 was 1412
      bp with an open reading frame of 657 bp encoding a putative protein of 219 amino
      acids (Accession no: KP898414). The calculated molecular mass of the PfBCL-2 was
      24.2 kDa with a predicted isoelectric point of 5.27. The deduced PfBCL-2 protein
      exhibited four highly conserved BCL-2 homology domains, suggesting that PfBCL-2
      may play a similar role in the apoptotic-signaling pathway as in other species.
      Real-time PCR results showed that PfBCL-2 transcript was expressed in a wide
      range of tissues but exhibited the greatest level of expression in blood.
      Transcriptional responses of PfBCL-2 exhibited different spatial and temporal
      expression profiles in liver and blood after bacterial infection. PfBcl-2
      transcript was significantly up-regulated in liver at 6, 12, 24 and 48 h (with
      maximum induction at 48 h) and was up-regulated in blood at 3, 6, 12 and 24 h
      (with maximum induction at 12 h). Meanwhile, recombinant PfBCL-2 fused with His6
      tag was efficiently expressed in Escherichia coli BL21 (DE3) and purified using
      Ni-nitrilotriacetic acid resin. Western blot analysis indicated that its protein
      level appeared to be elevated during the initial bacterial infection. These
      results suggest that PfBCL-2 plays important roles in immune responses against
      bacteria challenge.

PMID- 25963944
TI  - Dutch translation and cross-cultural validation of the Adult Social Care Outcomes
      Toolkit (ASCOT).
AB  - BACKGROUND: The Adult Social Care Outcomes Toolkit was developed to measure
      outcomes of social care in England. In this study, we translated the four level
      self-completion version (SCT-4) of the ASCOT for use in the Netherlands and
      performed a cross-cultural validation. METHODS: The ASCOT SCT-4 was translated
      into Dutch following international guidelines, including two forward and back
      translations. The resulting version was pilot tested among frail older adults
      using think-aloud interviews. Furthermore, using a subsample of the Dutch ACT
      study, we investigated test-retest reliability and construct validity and
      compared response distributions with data from a comparable English study.
      RESULTS: The pilot tests showed that translated items were in general understood
      as intended, that most items were reliable, and that the response distributions
      of the Dutch translation and associations with other measures were comparable to
      the original English version. Based on the results of the pilot tests, some small
      modifications and a revision of the Dignity items were proposed for the final
      translation, which were approved by the ASCOT development team. The complete
      original English version and the final Dutch translation can be obtained after
      registration on the ASCOT website ( http://www.pssru.ac.uk/ascot ). CONCLUSIONS:
      This study provides preliminary evidence that the Dutch translation of the ASCOT
      is valid, reliable and comparable to the original English version. We recommend
      further research to confirm the validity of the modified Dutch ASCOT translation.

PMID- 25963945
TI  - Rotavirus genotypes and the indigenous children of Brazilian midwest in the
      vaccine era, 2008-2012: Footprints of animal genome.
AB  - World group A rotavirus (RVA) surveillance data provides useful estimates of the
      disease burden, however, indigenous population might require special
      consideration. The aim of this study was to describe the results of G- and P
      types from Brazilian native children <= 3 years. Furthermore, selected strains
      have been analyzed for the VP7, VP6, VP4, and NSP4 encoding genes in order to
      gain insight into genetic variability of Brazilian strains. A total of 149
      samples, collected during 2008-2012, were tested for RVA using ELISA and PAGE,
      following by RT-PCR and sequencing. RVA infection was detected in 8.7% of samples
      (13/149). Genotype G2P[4] was detected in 2008 and 2010, G8P[6] in 2009, and
      G3P[8] in 2011. The phylogenetic analysis of the VP7 and VP4 genes grouped the
      Brazilian G2P[4] and G3P[8] strains within the lineages currently circulating in
      humans worldwide. However, the phylogenetic analysis of the VP6 and NSP4 from the
      Brazilian G2P[4] strains, and the VP7 and NSP4 from the Brazilian G3P[8] strains
      suggest a distant common ancestor with different animal strains (bovine, caprine,
      and porcine). The epidemiological and genetic information obtained in the present
      study is expected to provide an updated understanding of RVA genotypes
      circulating in the native infant population, and to formulate policies for the
      use of RVA vaccines in indigenous Brazilian people. Moreover, these results
      highlight the great diversity of human RVA strains circulating in Brazil, and an
      in-depth surveillance of human and animal RVA will lead to a better understanding
      of the complex dynamics of RVA evolution.

PMID- 25963946
TI  - Oleuropein and hydroxytyrosol protect from bisphenol A effects in livers and
      kidneys of lactating mother rats and their pups'.
AB  - Bisphenol A (BPA) is a chemical found in hard plastics and the coatings of food
      and drinks cans which can behave in a similar way to estrogen and other hormones
      in the human body. This study aimed to evaluate the significance of the treatment
      with oleuropein and hydroxytyrosol olive leaves rich extracts in reducing
      functional perturbations and oxidative stress arising from BPA treatment in
      livers and kidneys of lactating mother rats and their pups'. For this, four
      groups of lactating mothers were used: controls (group A), treated with bisphenol
      A (group B), treated with bisphenol A and oleuropein (group C) and with bisphenol
      A and hydroxytyrosol (group D). As results, we had found, in BPA treated group,
      either in mothers or in their pups', a significant decrease in morphological
      parameters, in catalase activity and in total antioxidant capacity associated to
      an increase in malondialdehyde levels in livers and kidneys. For these rats, the
      histological aspect showed, also, deep changes. Indeed, we had observed, in
      livers, hepatocellular necrosis associated to leucocytes infiltration and in
      kidneys tubular and glomerular necrosis. The co-treatments with BPA and
      oleuropein (group C) or with BPA and hydroxytyrosol (group D) ameliorate all
      morphological, biochemical and histological parameters as compared to BPA treated
      group B. The analysis of BPA and its derivatives with LC-MS/MS showed changes in
      their localizations between serum, livers or kidneys in all studied groups. In
      conclusion, the present study demonstrates the hepato-protective and reno
      protective effects of oleuropein and hydroxytyrosol olive leaves extracts from
      BPA and its derivates toxicity. 

PMID- 25963947
TI  - Ciliatoxicity in human primary bronchiolar epithelial cells after repeated
      exposure at the air-liquid interface with native mainstream smoke of K3R4F
      cigarettes with and without charcoal filter.
AB  - Mucociliary clearance is the primary physical mechanism to protect the human
      airways against harmful effects of inhaled particles. Environmental factors play
      a significant role in the impairment of this defense mechanism, whereas cigarette
      smoke is discussed to be one of the clinically most important causes. Impaired
      mucociliary clearance in smokers has been connected to changes in ciliated cells
      such as decreased numbers, altered structure and beat frequency. Clinical studies
      have shown that cilia length is reduced in healthy smokers and that long-term
      exposure to cigarette smoke leads to reduced numbers of ciliated cells in mice.
      We present an in vitro model of primary normal human bronchiolar epithelial
      (NHBE) cells with in vivo like morphology to study the influence of cigarette
      mainstream smoke on ciliated cells. We exposed mucociliary differentiated
      cultures repeatedly to non-toxic concentrations of mainstream cigarette smoke (4
      cigarettes, 5 days/week, 8 repetitions in total) at the air-liquid interface.
      Charcoal filter tipped cigarettes were compared to those being equipped with
      standard cellulose acetate filters. Histopathological analyses of the exposed
      cultures showed a reduction of cilia bearing cells, shortening of existing cilia
      and finally disappearance of all cilia in cigarette smoke exposed cells. In
      cultures exposed to charcoal filtered cigarette smoke, little changes in cilia
      length were seen after four exposure repetitions, but those effects were reversed
      after a two day recovery period. Those differences indicate that volatile organic
      compounds, being removed by the charcoal filter tip, affect primary bronchiolar
      epithelial cells concerning their cilia formation and function comparable with
      the in vivo situation. In conclusion, our in vitro model presents a valuable tool
      to study air-borne ciliatoxic compounds. 

PMID- 25963948
TI  - Folic Acid Supplementation Ameliorates Oxidative Stress, Metabolic Functions and
      Developmental Anomalies in a Novel Fly Model of Parkinson's Disease.
AB  - Mutations in parkin cause early-onset Parkinson's disease. Studies involving
      Drosophila model have emphasised mitochondrial dysfunction as a critical event in
      disease pathogenesis. In this context, we employed a novel recessive allele of
      parkin, park (c00062) , for the current study. The piggyBac insertion at 3rd
      intron of parkin in park (c00062) was confirmed by PCR. Homozygous park (c00062)
      has diminished levels of truncated parkin transcript with no detectable protein
      as confirmed by qRT-PCR and western blot analysis, respectively. The homozygous
      park (c00062) displayed severe developmental anomalies involving reduced body
      size, ~45 % pupal lethality, high mortality with locomotory defect, elevated
      oxidative stress, low metabolic active cell status with low mitochondrial
      respiration as reflected from reduced ATP levels. Further, folic acid therapeutic
      potential was analysed in park (c00062) . Here we show that dietary folic acid
      provided protection against disparities involving pupal lethality, high
      mortality, locomotory defect, elevated oxidative stress and low metabolic active
      cell status associated with park (c00062) . Further mitochondrial respiration was
      enhanced as reflected from improved ATP levels in folate supplemented park
      (c00062) . To corroborate mitochondrial functioning further our analysis
      regarding transcript status of p53 and spargel by qRT-PCR, revealed down
      regulation of p53 and up regulation of spargel in folate supplemented park
      (c00062) , which was originally vice a versa. Our data thus support the potential
      of FA in alleviating the disparities associated with parkin loss of function in
      fly model. Further, FA role in alleviating mitochondrial dysfunction is
      encouraging to further explore FA mechanistic role to be utilized as potential
      therapeutics for parkin mediated neurodegenerative diseases. 

PMID- 25963950
TI  - Broadband light trapping based on periodically textured ZnO thin films.
AB  - Transparent conductive front electrodes (TCFEs) deployed in photovoltaic devices
      have been extensively studied for their significance in transporting carriers,
      coupling and trapping the incident photons in high-performing solar cells. The
      trade-off between the light-transmission, electrical, and scattering properties
      for TCFEs to achieve a broadband improvement in light absorption in solar cells
      while maintaining a high electrical performance has become the key issue to be
      tackled. In this paper, we employ self-assembled polystyrene (PS) spheres based
      on a sauna-like method as a template, followed by a double-layer deposition and
      then successfully fabricate highly-transparent, well-conductive, and large-scale
      periodically-textured ZnO TCFEs with broadband light trapping properties. A sheet
      resistance below 15 Omega sq(-1) was achieved for the periodically-textured ZnO
      TCFEs, with a concomitant average transmission of 81% (including the glass
      substrate) in the 400-1100 nm spectral range, a haze improvement in a broadband
      spectral range, and a wider scattering angular domain. The proposed approach
      affords a promising alternative method to prepare periodically-textured TCFEs,
      which are essential for many optoelectronic device semiconductors, such as
      photovoltaic and display applications. 

PMID- 25963949
TI  - Epigenetic Regulation of Dopamine Transporter mRNA Expression in Human
      Neuroblastoma Cells.
AB  - The dopamine transporter (DAT) is a key regulator of dopaminergic
      neurotransmission. As such, proper regulation of DAT expression is important to
      maintain homeostasis, and disruption of DAT expression can lead to
      neurobehavioral dysfunction. Based on genomic features within the promoter of the
      DAT gene, there is potential for DAT expression to be regulated through
      epigenetic mechanisms, including DNA methylation and histone acetylation.
      However, the relative contribution of these mechanisms to DAT expression has not
      been empirically determined. Using pharmacologic and genetic approaches, we
      demonstrate that inhibition of DNA methyltransferase (DNMT) activity increased
      DAT mRNA approximately 1.5-2 fold. This effect was confirmed by siRNA knockdown
      of DNMT1. Likewise, the histone deacetylase (HDAC) inhibitors valproate and
      butyrate also increased DAT mRNA expression, but the response was much more
      robust with expression increasing over tenfold. Genetic knockdown of HDAC1 by
      siRNA also increased DAT expression, but not to the extent seen with
      pharmacological inhibition, suggesting additional isoforms of HDAC or other
      targets may contribute to the observed effect. Together, these data identify the
      relative contribution of DNMTs and HDACs in regulating expression. These finding
      may aid in understanding the mechanistic basis for changes in DAT expression in
      normal and pathophysiological states. 

PMID- 25963951
TI  - Sleep, circadian rhythms and alcohol: introduction and overview.

PMID- 25963952
TI  - Efficacy and safety of cord blood-derived cytokine-induced killer cells in
      treatment of patients with malignancies.
AB  - BACKGROUND AIMS: Adoptive immunotherapy with the use of cytokine-induced killer
      (CIK) cells represents an effective therapeutic option for treating malignancies.
      The characteristics and function of cord blood-derived CIK (CB-CIK) cells have
      been evaluated both in vitro and in vivo. In this study, we assessed the efficacy
      and safety of administering CB-CIK cells to patients with cancer. METHODS: In
      this retrospective clinical trial, 15 patients with cancer received CB-CIK
      therapy with different cycles from April 2012 to August 2014. CB-CIK cells
      demonstrated a high percentage of main functional fraction CD3(+)CD56(+) and
      efficient anti-tumor activity in vitro. RESULTS: After the infusion of CB-CIK
      cells, the subsets of CD3(+)CD4(+) T lymphocytes and CD3(-)CD56(+) T cells in the
      peripheral blood were significantly increased compared with those before the
      therapy. Of 15 patients, one patient with hepatocellular cancer and one patient
      with esophageal cancer achieved complete responses, two patients with ovarian
      cancer obtained partial remissions, 10 patients had stable disease and one
      patient with hepatocellular cancer had progressive disease. Acute toxicities
      including fever, slight fever, dizziness and other neurologic toxicities were few
      and occurred in patients after infusion of CB-CIK cells. CONCLUSIONS: These
      results demonstrated the feasibility and safety of treating malignancies with CB
      CIK cells. The study provides a potential therapeutic approach for the patients
      with poor health or older patients who cannot tolerate repeated collection of
      blood.

PMID- 25963953
TI  - Pigtails Internal Drainage for 2-cm Gastric Leak After Sleeve Gastrectomy
      Prolongs Healing.

PMID- 25963954
TI  - Endoscopic retrieval of a migrated esophageal stent using another anchored
      esophageal stent and an enteroscopy overtube: A novel technique.

PMID- 25963955
TI  - Progesterone-induced transdifferentiation of bone marrow stromal cells into
      Schwann cells improves sciatic nerve transection outcome in a rat model.
AB  - BACKGROUND: Peripheral nerve injury is a common lesion in clinical practice and
      transplantation is one of the most common approaches to its treatment. While
      nerve graft is used for restoring the defected nerve using autologous or
      allogenic tissues, Schwann cells are considered as an alternative source. In this
      study, bone marrow stromal cells (BMSCs) were induced to transdifferentiate into
      Schwann-like cells (SLCs) using progesterone. METHODS: The BMSCs were collected
      from the long bones of rats and were transdifferentiated in vitro into SLCs by
      preinduction with beta-mercaptoethanol and retinoic acid, followed by induction
      with bFGF, PDGF, forskelin and progesterone. The SLCs were then transplanted in a
      rat model of sciatic nerve injury with 1-cm gaps. A sciatic function index (SFI),
      histological, immunohistochemical and ultrastructural studies were used in
      evaluating the improvement in the nerves regeneration. RESULTS: The results show
      significant differences in the SFI between the control and the treated groups
      (P<0.05). The transplant was immunoreactive to S100, and the electron microscopy
      showed myelination in the transplanted cells. CONCLUSIONS: There were functional
      and structural improvements in the progesterone-induced SLCs, which were not
      significantly different from the heregulin-treated ones (positive control) but
      still significantly different from negative controls.

PMID- 25963956
TI  - The hemorrhage risk of prophylactic external ventricular drain insertion in
      aneurysmal subarachnoid hemorrhage patients requiring endovascular aneurysm
      treatment: a systematic review and meta-analysis.
AB  - INTRODUCTION: Endovascular treatment of acutely ruptured aneurysms requires the
      administration of antiplatelet and/or anticoagulant medication to prevent
      thrombosis. For patients who require an external ventricular drain (EVD)
      insertion to treat hydrocephalus stemming from aneurysm subarachnoid hemorrhage
      (aSAH), the administration of the medication may increase risk of hemorrhage in
      patients. It has become a practice for neurosurgeons to insert EVDs in patients
      with aSAH before endovascular treatment. However, the benefits and risks of this
      practice have not been fully assessed. The aim of this study was to compare and
      quantify the hemorrhagic risks associated with endovascular treatment of patients
      with sSAH before and after EVD. EVIDENCE ACQUISITION: This is a systematic review
      and meta-analysis. The literature was searched for studies with EVD and non-EVD
      patients with ruptured aneurysms undergoing endovascular treatment of aneurysms.
      A qualitative and quantitative assessment of EVD-related hemorrhage risk before
      and after endovascular treatment was undergone. EVIDENCE SYNTHESIS: There seemed
      to be a stronger correlation between EVD-related hemorrhage and EVD insertion
      after endovascular treatment (cumulative relative risk: 9.61; 95% CI: 2.29,
      40.24) compared to EVD insertion before endovascular treatment (cumulative
      relative risk: 2.37; 95% CI: 0.57, 9.81). CONCLUSIONS: EVD-related hemorrhage
      risk may increase with administration of antiplatelet and/or anticoagulant
      medication for endovascular treatment of ruptured aneurysms in aSAH patients.

PMID- 25963957
TI  - Study of modified electroconvulsive therapy combined with risperidone oral
      solution in the treatment of agitation in the acute stage of epilepsy and
      expression level changes of insulin-like growth factor-1.
AB  - BACKGROUND: The aim of this paper was to explore the efficacy of modified
      electroconvulsive therapy (MECT) combined with risperidone oral solution in the
      treatment of agitation in the acute stage of epilepsy, and the effects of insulin
      like growth factor-1 mRNA and protein expression. METHODS: Forty-six cases with
      seizures and agitation in the acute stage were included from February 2012 to
      February 2014. This study was approved by the ethics committee in our hospital.
      Patients were divided randomly into the experimental (23 cases) and control (23
      cases) groups. The patients in the experimental group were treated with MECT
      combined with risperidone oral solution. The patients in the control group were
      treated with risperidone oral solution. The Positive and Negative Symptom Scale
      (PANSS) score and Treatment-Emergent Symptom Scale (TESS) score were compared
      before and after treatment. The insulin-like growth factor-1 (IGF-1) protein and
      mRNA expression level were detected with enzyme-linked immunosorbent assay
      (ELISA) and qRT-PCR, respectively. RESULTS: There were no significant differences
      on positive and negative symptom scores or total score in the two groups before
      treatment (P>0.05). After treatment, the positive symptom score, negative symptom
      score, and total score all decreased in both groups, and the decrease was more
      obvious in the experimental group (P<0.05). After treatment, TESS scores of the
      experimental group were significantly lower than those of the control group
      (P<0.05). In the experimental group, the total efficiency was significantly
      higher than that in the control group (P<0.05). Before treatment, there were no
      significant differences in the expression levels of IGF-1 protein or mRNA in the
      two groups (P>0.05), while after treatment the expression levels of IGF-1 protein
      and mRNA decreased in both groups. However, the decrease was more obvious in the
      experimental group. The differences were all significant for scores (P<0.05).
      CONCLUSIONS: The combined application of MECT and risperidone oral solution in
      the treatment of agitation can improve the clinical efficacy to some extent.

PMID- 25963958
TI  - Impact of World War I on Brain Mapping.
AB  - Although much tragedy was experienced during World War I (WWI), the nature of the
      war and the advancements of weaponry led to a change in the quality and quantity
      of injuries which were conducive for study. This paper discusses how trauma
      during WWI led to advances in brain mapping from occipital injuries. Gordon
      Holmes was a British neurologist who was able to create a retinotopic map of the
      visual cortex from studying more than 400 cases of occipital injuries; his work
      has contributed immensely to our understanding of visual processing. There have
      been many extensions from Holmes' work in regards to how we analyze other sensory
      modalities and in researching how the brain processes complex stimuli such as
      faces. Aside from the scholastic benefit, brain mapping also has functional use
      and can be used for neurosurgical planning to preserve important structures. With
      the advent of more advanced modalities for analyzing the brain, there have been
      initiatives in total brain mapping which has added significantly to the body of
      work started by Holmes during WWI. This paper reviews the history during WWI that
      led to advances in brain mapping, the lasting scholastic and functional impact
      from these advancements, and future improvements.

PMID- 25963959
TI  - Prostate cancer: Selenium, lycopene and GTC-a case of 'chemopromotion'.

PMID- 25963963
TI  - Infection: Ceftolozane-tazobactam gives a new ASPECT to the fight against
      antimicrobial resistance.

PMID- 25963966
TI  - Incontinence: Fixing fistulas-shorter hospital stay is feasible.

PMID- 25963964
TI  - Urinary considerations for adult patients with spinal dysraphism.
AB  - The incidence of newborns with spinal dysraphism is diminishing worldwide,
      although survival of individuals with this condition into adulthood continues to
      improve. The number of adults with spinal dysraphism will, therefore, increase in
      the coming years, which will pose new challenges in patient management.
      Urological manifestations of spinal dysraphism can include increased risks of
      urinary incontinence, urinary tract infection, urinary calculi, sexual
      dysfunction, end-stage renal disease and iatrogenic metabolic disturbances;
      however, the severity and incidence of these symptoms varies substantially
      between patients. Owing to the presence of multiple comorbidities, treatment and
      follow-up protocols often have to be adapted to best suit the needs of specific
      patients. Authors describe bladder and kidney function and long-term
      complications of treatments initiated in childhood, as well as the potential for
      improvements in quality of life through better follow-up schedules and future
      developments. 

PMID- 25963967
TI  - Pain: BoNT-A reduces pain in patients with treatment refractory IC/BPS.

PMID- 25963968
TI  - Enhanced antitumor immunity of nanoliposome-encapsulated heat shock protein 70
      peptide complex derived from dendritic tumor fusion cells.
AB  - Tumor-derived heat shock proteins peptide complex (HSP.PC-Tu) has been regarded
      as a promising antitumor agent. However, inadequate immunogenicity and low
      bioavailability limit the clinical uses of this agent. In a previous study, we
      first produced an improved HSP70.PC-based vaccine purified from dendritic cell
      (DC)-tumor fusion cells (HSP70.PC-Fc) which had increased immunogenicity due to
      enhanced antigenic tumor peptides compared to HSP70.PC-Tu. In order to increase
      the bioavailability of HSP70.PC-Fc, the peptide complex was encapsulated with
      nanoliposomes (NL-HSP70.PC-Fc) in this study. After encapsulation, the tumor
      immunogenicity was observed using various assays. It was demonstrated that the NL
      HSP70.PC-Fc has acceptable stability. The in vivo antitumor immune response was
      increased with regard to T-cell activation, CTL response and tumor therapy
      efficiency compared to that of HSP70.PC-Fc. In addition, it was shown that DC
      maturation was improved by NL-HSP70.PC-Fc, which added to the antitumor immunity.
      The results obtained for NL-HSP70.PC-Fc, which improved immunogenicity and
      increases the bioavailability of HSP70.PC, may represent superior heat shock
      proteins (HSPs)-based tumor vaccines. Such vaccines deserve further investigation
      and may provide a preclinical rationale to translate findings into early phase
      trials for patients with breast tumors.

PMID- 25963969
TI  - Comparative effectiveness of urate lowering with febuxostat versus allopurinol in
      gout: analyses from large U.S. managed care cohort.
AB  - INTRODUCTION: To assess the comparative effectiveness of febuxostat and
      allopurinol in reducing serum urate (sUA) levels in a real-world U.S. managed
      care setting. METHODS: This retrospective study utilized 2009 to 2012 medical and
      pharmacy claims and laboratory data from a large U.S. commercial and Medicare
      Advantage health plan. Study patients had at least one medical claim with a
      diagnosis of gout, at least one filled prescription for febuxostat or allopurinol
      and at least one sUA measurement post-index prescription. Reduction in sUA was
      examined using propensity score-matched cohorts, matched on patient demographics
      (gender, age), baseline sUA, comorbidities, geographic region and insurance type.
      RESULTS: The study sample included 2,015 patients taking febuxostat and 14,025
      taking allopurinol. At baseline, febuxostat users had a higher Quan-Charlson
      comorbidity score (0.78 vs. 0.53; P <0.001), but similar age and gender
      distribution. Mean (standard deviation (SD)) sUA level following propensity score
      matching among treatment-naive febuxostat vs. allopurinol users (n = 873 each)
      were: pre-index sUA, 8.86 (SD, 1.79) vs. 8.72 (SD, 1.63; P = 0.20); and post
      index sUA, 6.53 (SD, 2.01) vs. 6.71 (SD, 1.70; P = 0.04), respectively. A higher
      proportion of febuxostat users attained sUA goals of <6.0 mg/dl (56.9% vs. 44.8%;
      P <0.001) and <5.0 mg/dl (35.5% vs. 19.2%; P <0.001), respectively. Time to
      achieve sUA goals of <6.0 mg/dl (346 vs. 397 days; P <0.001) and <5.0 mg/dl was
      shorter in febuxostat vs. allopurinol users (431 vs. 478 days; P <0.001),
      respectively. Similar observations were made for overall propensity score-matched
      cohorts that included both treatment-naive and current users (n = 1,932 each).
      CONCLUSIONS: Febuxostat was more effective than allopurinol at the currently used
      doses (40 mg/day for febuxostat in 83% users and 300 mg/day or lower for
      allopurinol in 97% users) in lowering sUA in gout patients as demonstrated by
      post-index mean sUA level, the likelihood of and the time to achieving sUA goals.

PMID- 25963973
TI  - Impact of leukemia and lymphoma chemotherapy on oral cavity and quality of life.
AB  - This study aimed to understand how patients perceive their oral health and the
      resulting oral manifestations of antineoplastic chemotherapy, as well as to
      analyze the impact of these alterations on oral health-related quality of life. A
      total of 80 patients undergoing treatment participated in this study. A
      questionnaire was applied using the Oral Health Impact Profile (OHIP-14) index
      and open interviews. Items with the highest impact prevalence included "worsened
      taste of food sensation" (35.00%), "discomfort in eating food" (20.00%), and
      "feeling stressed" (17.50%). The outpatients showed the highest prevalence
      scores, whereas the inpatients presented higher quality of life impact severity.
      The ways in which the patients perceived how their oral alteration affected their
      quality of life were distinct and subjective. It is important that dentists act
      together with a multiprofessional team developing strategies to alleviate the
      impact of the disease and chemotherapy on oral cavity and patients' quality of
      life.

PMID- 25963972
TI  - Genetics of skin color variation in Europeans: genome-wide association studies
      with functional follow-up.
AB  - In the International Visible Trait Genetics (VisiGen) Consortium, we investigated
      the genetics of human skin color by combining a series of genome-wide association
      studies (GWAS) in a total of 17,262 Europeans with functional follow-up of
      discovered loci. Our GWAS provide the first genome-wide significant evidence for
      chromosome 20q11.22 harboring the ASIP gene being explicitly associated with skin
      color in Europeans. In addition, genomic loci at 5p13.2 (SLC45A2), 6p25.3 (IRF4),
      15q13.1 (HERC2/OCA2), and 16q24.3 (MC1R) were confirmed to be involved in skin
      coloration in Europeans. In follow-up gene expression and regulation studies of
      22 genes in 20q11.22, we highlighted two novel genes EIF2S2 and GSS, serving as
      competing functional candidates in this region and providing future research
      lines. A genetically inferred skin color score obtained from the 9 top-associated
      SNPs from 9 genes in 940 worldwide samples (HGDP-CEPH) showed a clear gradual
      pattern in Western Eurasians similar to the distribution of physical skin color,
      suggesting the used 9 SNPs as suitable markers for DNA prediction of skin color
      in Europeans and neighboring populations, relevant in future forensic and
      anthropological investigations. 

PMID- 25963974
TI  - Management of Bartholin's cyst and abscess using the Word catheter:
      implementation, recurrence rates and costs.
AB  - OBJECTIVE: Bartholin's cysts and abscesses occur in about 2% of women. None of
      the surgical or conservative treatment approaches have been proven to be
      superior. The Word catheter is an outpatient treatment option, but little is
      known about aspects of implementing this therapy in an office setting. The
      present study's focus is on recurrence rates and organizational requirements of
      implementing outpatient treatment of Bartholin's cyst and abscess and compares
      costs of Word catheter treatment and marsupialization. STUDY DESIGN: Between
      March 2013 and May 2014 30 women were included in the study. We measured time
      consumed for treatment and follow-up and analyzed costs using the Word catheter
      and marsupialization under general anesthesia. We also assessed the ease of use
      of the Word catheter for application and removal using a standardized visual
      analog scale (VAS 1-10). RESULTS: Word catheter treatment was successful in 26/30
      cases (87%). Balloon loss before the end of the 4-week treatment period occurred
      in 11/26 cases with a mean residence time of 19.1 (+/-10.0) days. None of the
      patients with early catheter loss developed recurrent cyst or abscess. Recurrence
      occurred in 1/26 cases (3.8%). Difficulty-score of application was 2 [1-10] and
      of removal 1 [1], respectively. Costs were ? 216 for the treatment in the clinic
      as compared with ? 1584/? 1282 for surgical marsupialization with a one-night
      stay or daycare clinic, respectively. CONCLUSIONS: The present study indicates
      that the Word catheter is an easy to handle, low cost outpatient procedure with
      acceptable short-term recurrence rates. Treatment costs are seven times lower
      than for marsupialization.

PMID- 25963975
TI  - Species Tree Inference Using a Mixture Model.
AB  - Species tree reconstruction has been a subject of substantial research due to its
      central role across biology and medicine. A species tree is often reconstructed
      using a set of gene trees or by directly using sequence data. In either of these
      cases, one of the main confounding phenomena is the discordance between a species
      tree and a gene tree due to evolutionary events such as duplications and losses.
      Probabilistic methods can resolve the discordance by coestimating gene trees and
      the species tree but this approach poses a scalability problem for larger data
      sets. We present MixTreEM-DLRS: A two-phase approach for reconstructing a species
      tree in the presence of gene duplications and losses. In the first phase,
      MixTreEM, a novel structural expectation maximization algorithm based on a
      mixture model is used to reconstruct a set of candidate species trees, given
      sequence data for monocopy gene families from the genomes under study. In the
      second phase, PrIME-DLRS, a method based on the DLRS model (Akerborg O, Sennblad
      B, Arvestad L, Lagergren J. 2009. Simultaneous Bayesian gene tree reconstruction
      and reconciliation analysis. Proc Natl Acad Sci U S A. 106(14):5714-5719), is
      used for selecting the best species tree. PrIME-DLRS can handle multicopy gene
      families since DLRS, apart from modeling sequence evolution, models gene
      duplication and loss using a gene evolution model (Arvestad L, Lagergren J,
      Sennblad B. 2009. The gene evolution model and computing its associated
      probabilities. J ACM. 56(2):1-44). We evaluate MixTreEM-DLRS using synthetic and
      biological data, and compare its performance with a recent genome-scale species
      tree reconstruction method PHYLDOG (Boussau B, Szollosi GJ, Duret L, Gouy M,
      Tannier E, Daubin V. 2013. Genome-scale coestimation of species and gene trees.
      Genome Res. 23(2):323-330) as well as with a fast parsimony-based algorithm
      Duptree (Wehe A, Bansal MS, Burleigh JG, Eulenstein O. 2008. Duptree: a program
      for large-scale phylogenetic analyses using gene tree parsimony. Bioinformatics
      24(13):1540-1541). Our method is competitive with PHYLDOG in terms of accuracy
      and runs significantly faster and our method outperforms Duptree in accuracy. The
      analysis constituted by MixTreEM without DLRS may also be used for selecting the
      target species tree, yielding a fast and yet accurate algorithm for larger data
      sets. MixTreEM is freely available at http://prime.scilifelab.se/mixtreem/. 

PMID- 25963976
TI  - A Cascade of epistatic interactions regulating teratozoospermia in mice.
AB  - Infertility in humans and subfertility in domestic animals are two major
      reproductive problems. Among human couples, ~15% are diagnosed as infertile, and
      males are considered responsible in about 50% of the cases. To examine male
      fertility, various sperm tests including analyses of sperm morphology, sperm
      count and sperm mobility are usually performed. Teratozoospermia, a condition
      characterized by the presence of morphologically abnormal sperm, is considered as
      a symptom of infertility. B10.MOL-TEN1 (TEN1) mice (Mus musculus) show inherited
      teratozoospermia at high frequencies (~50%). In this study, the polygenic control
      of teratozoospermia in the TEN1 strain was analysed. A quantitative trait loci
      analysis indicated three statistically significant loci, Sperm-head morphology 3
      (Shm3; logarithm of the odds (LOD) score, 29.25), Shm4 (LOD score, 6.80), and
      Shm5 (LOD score, 3.58). These three QTL peaks were mapped to 24.3 centimorgans
      (cM) on chromosome 1, 32.0 cM on chromosome X, and 63.8 cM on chromosome 6,
      respectively. Another locus that is yet to be determined was also predicted. Shm3
      was found to be the major locus responsible for teratozoospermia, and a
      sequential cascade of interactions of the other three loci was apparent. These
      results are expected to help understand the mechanisms underlying reproductive
      problems in humans or domestic animals.

PMID- 25963977
TI  - Genomic regulation of senescence and innate immunity signaling in the retinal
      pigment epithelium.
AB  - The tumor suppressor p53 is a major regulator of genes important for cell cycle
      arrest, senescence, apoptosis, and innate immunity, and has recently been
      implicated in retinal aging. In this study we sought to identify the genetic
      networks that regulate p53 function in the retina using quantitative trait locus
      (QTL) analysis. First we examined age-associated changes in the activation and
      expression levels of p53; known p53 target proteins and markers of innate immune
      system activation in primary retinal pigment epithelial (RPE) cells that were
      harvested from young and aged human donors. We observed increased expression of
      p53, activated caspase-1, CDKN1A, CDKN2A (p16INK4a), TLR4, and IFNalpha in aged
      primary RPE cell lines. We used the Hamilton Eye Institute (HEI) retinal dataset
      ( www.genenetwork.org ) to identify genomic loci that modulate expression of
      genes in the p53 pathway in recombinant inbred BXD mouse strains using a QTL
      systems biology-based approach. We identified a significant trans-QTL on
      chromosome 1 (region 172-177 Mb) that regulates the expression of Cdkn1a. Many of
      the genes in this QTL locus are involved in innate immune responses, including Fc
      receptors, interferon-inducible family genes, and formin 2. Importantly, we found
      an age-related increase in FCGR3A and FMN2 and a decrease in IFI16 levels in RPE
      cultures. There is a complex multigenic innate immunity locus that controls
      expression of genes in the p53 pathway in the RPE, which may play an important
      role in modulating age-related changes in the retina.

PMID- 25963978
TI  - Enhanced expression of cohesin loading factor NIPBL confers poor prognosis and
      chemotherapy resistance in non-small cell lung cancer.
AB  - BACKGROUND: NIPBL, the sister chromatid cohesion 2 (SCC2) human homolog, is a
      cohesin loading factor which is essential for deposition of cohesin onto the
      sister chromatid. Recent studies have shown that NIPBL contribute to sister
      chromatid cohesion and plays a critical role in development, DNA repair, and gene
      regulation. In this study, we measured the expression of NIPBL in clinical non
      small cell lung cancer specimens, and determined its effects on cellular
      processes and chemosensitivity in vitro. METHODS: NIPBL immunohistochemistry was
      performed on 123 lung adenocarcinoma samples. Through knockdown of NIPBL protein
      expression, non-small cell lung cancer cell lines were used to test the potential
      involvement of NIPBL silencing on cell proliferation, migration, invasion, and
      apoptosis. Chemosensitivity was assessed with clonogenic assays, and chromatin
      immunoprecipitation assays were performed to analyze the relationship between
      NIPBL and signal transducers and activators of transcription 3 (STAT3). RESULTS:
      Immunohistochemical analysis showed that high expression of NIPBL was strongly
      correlated with poor prognosis, tumor differentiation, and lymph node metastasis.
      Survival analysis further indicated that NIPBL expression was a potential
      prognostic factor for non-small cell lung cancer. Knockdown of NIPBL in non-small
      cell lung cancer cell lines significantly reduced cellular proliferation,
      migration, and invasion, and enhanced cellular apoptosis and sensitivity to
      cisplatin, paclitaxel, and gemcitabine hydrochloride. NIPBL bound to the promoter
      region of the STAT3 gene, directly regulating the expression of STAT3.
      CONCLUSIONS: These data suggested that NIPBL played a significant role in lung
      carcinogenesis. NIPBL expression conferred poor prognosis and resistance to
      chemotherapy in non-small cell lung cancer, suggesting that NIPBL may be a novel
      therapeutic target.

PMID- 25963979
TI  - Human keratin 8 variants promote mouse acetaminophen hepatotoxicity coupled with
      c-jun amino-terminal kinase activation and protein adduct formation.
AB  - Keratins 8 and 18 (K8/K18) are the intermediate filaments proteins of simple-type
      digestive epithelia and provide important cytoprotective function. K8/K18
      variants predispose humans to chronic liver disease progression and poor outcomes
      in acute acetaminophen (APAP)-related liver failure. Given that K8 G62C and
      R341H/R341C are common K8 variants in European and North American populations, we
      studied their biological significance using transgenic mice. Mice that
      overexpress the human K8 variants, R341H or R341C, were generated and used
      together with previously described mice that overexpress wild-type K8 or K8 G62C.
      Mice were injected with 600 mg/kg of APAP or underwent bile duct ligation (BDL).
      Livers were evaluated by microarray analysis, quantitative real-time polymerase
      chain reaction, immunoblotting, histological and immunological staining, and
      biochemical assays. Under basal conditions, the K8 G62C/R341H/R341C variant
      expressing mice did not show an obvious liver phenotype or altered keratin
      filament distribution, whereas K8 G62C/R341C animals had aberrant disulphide
      cross-linked keratins. Animals carrying the K8 variants displayed limited gene
      expression changes, but had lower nicotinamide N-methyl transferase (NNMT) levels
      and were predisposed to APAP-induced hepatotoxicity. NNMT represents a novel
      K8/K18-associated protein that becomes up-regulated after K8/K18 transfection.
      The more pronounced liver damage was accompanied by increased and prolonged JNK
      activation; elevated APAP protein adducts; K8 hyperphosphorylation at S74/S432
      with enhanced keratin solubility; and prominent pericentral keratin network
      disruption. No differences in APAP serum levels, glutathione, or adenosine
      triphosphate levels were noted. BDL resulted in similar liver injury and biliary
      fibrosis in all mouse genotypes. CONCLUSION: Expression of human K8 variants
      G62C, R341H, or R341C in mice predisposes to acute APAP hepatotoxicity, thereby
      providing direct evidence for the importance of these variants in human acute
      liver failure.

PMID- 25963980
TI  - Pharmacokinetics of piperaquine transfer into the breast milk of Melanesian
      mothers.
AB  - Transfer of piperaquine (PQ) into breast milk was examined in 27 Papua New
      Guinean women given a 3-day course of dihydroartemisinin-PQ or sulfadoxine
      pyrimethamine-PQ during the second/third trimester. Breast milk was sampled on
      days 1, 2, 3 to 5, 7 to 11, and 14 to 17 postdelivery, a median of 70 days
      postdose (range, 6 to 145 days). A blood sample was taken at delivery, and
      additional serial samples were available from 9 women who delivered within 42
      days of dosing. Milk and plasma PQ were assayed by high-performance liquid
      chromatography. A population-based approach was used to model the loge(plasma)
      and milk concentration-time data. A sigmoid Emax model best described PQ breast
      milk transfer. The population average milk:plasma PQ ratio was 0.58, with a peak
      of 2.5 at delivery. The model-derived maximum milk intake (148 ml/kg of body
      weight/day) was similar to the accepted value of 150 ml/kg/day. The median
      estimated absolute and relative cumulative infant PQ doses were 22 MUg and 0.07%,
      respectively, corresponding to absolute and relative daily doses of 0.41 MUg/kg
      and 0.004%. Model-based simulations for PQ treatment regimens given at birth, 1
      week postdelivery, and 6 weeks postdelivery showed that the highest median
      estimated relative total infant dose (0.36%; median absolute total dose of 101
      MUg/kg) was seen after maternal PQ treatment 6 weeks postpartum. The maximum
      simulated relative total and daily doses from any scenario were 4.3% and 2.5%,
      respectively, which were lower than the recommended 10% upper limit. Piperaquine
      is transferred into breast milk after maternal treatment doses, but PQ exposure
      for suckling infants appears safe.

PMID- 25963981
TI  - Population pharmacokinetics, tolerability, and safety of dihydroartemisinin
      piperaquine and sulfadoxine-pyrimethamine-piperaquine in pregnant and nonpregnant
      Papua New Guinean women.
AB  - The tolerability, safety, and disposition of dihydroartemisinin (DHA) and
      piperaquine (PQ) were assessed in 32 pregnant (second/third trimester) and 33
      nonpregnant Papua New Guinean women randomized to adult treatment courses of DHA
      PQ (three daily doses) or sulfadoxine-pyrimethamine (SP)-PQ (three daily PQ
      doses, single dose of SP). All dose adminstrations were observed, and subjects
      fasted for 2 h postdose. Plasma PQ was assayed by using high-performance liquid
      chromatography, and DHA was assessed by using liquid chromatography-mass
      spectrometry. Compartmental pharmacokinetic models were developed using a
      population-based approach. Both regimens were well tolerated. There was an
      expected increase in the rate-corrected electrocardiographic QT interval which
      was independent of pregnancy and treatment. Two pregnant and two nonpregnant
      women had Plasmodium falciparum parasitemia which cleared within 48 h, and no
      other subject became slide positive for malaria during 42 days of follow-up. Of
      30 pregnant women followed to delivery, 27 (90%) delivered healthy babies and 3
      (10%) had stillbirths; these obstetric outcomes are consistent with those in the
      general population. The area under the plasma PQ concentration-time curve (AUC0
      infinity) was lower in the pregnant patients (median [interquartile range],
      23,721 MUg . h/liter [21,481 to 27,951 MUg . h/liter] versus 35,644 MUg . h/liter
      [29,546 to 39,541 MUg . h/liter]; P < 0.001) in association with a greater
      clearance relative to bioavailability (73.5 liters/h [69.4 to 78.4] versus 53.8
      liters/h [49.7 to 58.2]; P < 0.001), but pregnancy did not influence the
      pharmacokinetics of DHA. The apparent pharmacokinetic differences between the
      present study and results from other studies of women with uncomplicated malaria
      that showed no effect of pregnancy on the AUC0-infinity of PQ and greater
      bioavailability may reflect differences in postdose fat intake, proportions of
      women with malaria, and/or racial differences in drug disposition.

PMID- 25963982
TI  - In vitro activity of daptomycin in combination with beta-lactams, gentamicin,
      rifampin, and tigecycline against daptomycin-nonsusceptible enterococci.
AB  - Enterococci that are nonsusceptible (NS; MIC > 4 MUg/ml) to daptomycin are an
      emerging clinical concern. The synergistic combination of daptomycin plus beta
      lactams has been shown to be effective against vancomycin-resistant Enterococcus
      (VRE) species in vitro. This study systematically evaluated by in vitro time-kill
      studies the effect of daptomycin in combination with ampicillin, cefazolin,
      ceftriaxone, ceftaroline, ertapenem, gentamicin, tigecycline, and rifampin, for a
      collection of 9 daptomycin-NS enterococci that exhibited a broad range of MICs
      and different resistance-conferring mutations. We found that ampicillin plus
      daptomycin yielded the most consistent synergy but did so only for isolates with
      mutations to the liaFSR system. Daptomycin binding was found to be enhanced by
      ampicillin in a representative isolate with such mutations but not for an isolate
      with mutation to the yycFGHIJ system. In contrast, ampicillin enhanced the
      killing of the LL-37 human antimicrobial peptide against daptomycin-NS E. faecium
      with either the liaFSR or yycFGHIJ mutation. Antagonism was noted only for
      rifampin and tigecycline and only for 2 or 3 isolates. These data add support to
      the growing body of evidence indicating that therapy combining daptomycin and
      ampicillin may be helpful in eradicating refractory VRE infections.

PMID- 25963983
TI  - Evaluating the pharmacodynamic effect of antimalarial drugs in clinical trials by
      quantitative PCR.
AB  - The ongoing development of new antimalarial drugs and the increasing use of
      controlled human malaria infection (CHMI) studies to investigate their activity
      in early-stage clinical trials require the development of methods to analyze
      their pharmacodynamic effect. This is especially so for studies where
      quantitative PCR (qPCR) is becoming the preferred method for assessing parasite
      clearance as the study endpoint. We report the development and validation of an
      analytic approach for qPCR-determined parasite clearance data. First, in a
      clinical trial with the licensed antimalarial combination sulfadoxine
      pyrimethamine (S/P), qPCR data were collected from 12 subjects and used to
      determine qPCR replicate variability and to identify outliers. Then, an iterative
      analytic approach based on modeling the log-linear decay of parasitemia following
      drug treatment was developed to determine the parasite reduction ratio (PRR) and
      parasite clearance half-life, both measures of parasite clearance. This analytic
      approach was then validated with data from 8 subjects enrolled in a second study
      with the licensed antimalarial drug mefloquine. By this method, the PRR and
      parasite clearance half-lives for S/P and Mefloquine were determined to be 38,878
      (95% confidence interval [95% CI], 17,396 to 86,889) at 3.15 (95% CI, 2.93 to
      3.41) days and 157 (95% CI, 130 to 189) at 6.58 (95% CI, 6.35 to 6.83) days for
      the respective studies. No serious adverse events occurred in the two trials, and
      pharmacokinetic values were within expected ranges for sulfadoxine and
      pyrimethamine. The robust statistical method that we have developed to analyze
      qPCR-derived pharmacodynamic data from CHMI studies will facilitate the
      assessment of the activity of a range of experimental antimalarial drugs now
      entering clinical trials. (This trial was registered with the Australian New
      Zealand Clinical Trials Registry under registration numbers ACTRN12611001203943
      and ACTRN12612000323820.).

PMID- 25963984
TI  - In vitro activity of aztreonam-avibactam against a global collection of Gram
      negative pathogens from 2012 and 2013.
AB  - The combination of aztreonam plus avibactam is being developed for use in
      infections caused by metallo-beta-lactamase-producing Enterobacteriaceae strains
      that also produce serine beta-lactamases. The in vitro activities of aztreonam
      avibactam and comparator antimicrobials were determined against year 2012 and
      2013 clinical isolates of Enterobacteriaceae, Pseudomonas aeruginosa, and
      Acinetobacter baumannii using the broth microdilution methodology recommended by
      the Clinical and Laboratory Standards Institute (CLSI). A total of 28,501 unique
      clinical isolates were obtained from patients in 190 medical centers within 39
      countries. MIC90 values of aztreonam and aztreonam-avibactam against all
      collected isolates of Enterobacteriaceae (n = 23,516) were 64 and 0.12 MUg/ml,
      respectively, with 76.2% of the isolates inhibited by <=4 MUg/ml of aztreonam
      (the CLSI breakpoint) and 99.9% of the isolates inhibited by <=4 MUg/ml of
      aztreonam-avibactam using a fixed concentration of 4 MUg/ml of avibactam. The
      MIC90 was 32 MUg/ml for both aztreonam and aztreonam-avibactam against P.
      aeruginosa (n = 3,766). Aztreonam alone or in combination with avibactam had no
      in vitro activity against isolates of A. baumannii. PCR and sequencing were used
      to characterize 5,076 isolates for beta-lactamase genes. Aztreonam was not active
      against most Enterobacteriaceae isolates producing class A or class C enzymes
      alone or in combination with class B metallo-beta-lactamases. In contrast, >99%
      of Enterobacteriaceae isolates producing all observed Ambler classes of beta
      lactamase enzymes were inhibited by <=4 MUg/ml aztreonam in combination with
      avibactam, including isolates that produced IMP-, VIM-, and NDM-type metallo-beta
      lactamases in combination with multiple serine beta-lactamases.

PMID- 25963985
TI  - N-acetyltransferase genotypes and the pharmacokinetics and tolerability of para
      aminosalicylic acid in patients with drug-resistant pulmonary tuberculosis.
AB  - The aim of this study was to examine the relationships between N
      acetyltransferase genotypes, pharmacokinetics, and tolerability of granular slow
      release para-aminosalicylic acid (GSR-PAS) in tuberculosis patients. The study
      was a randomized, two-period, open-label, crossover design wherein each patient
      received 4 g GSR-PAS twice daily or 8 g once daily alternately. The PAS
      concentration-time profiles were modeled by a one-compartment disposition model
      with three transit compartments in series to describe its absorption. Patients'
      NAT1 and NAT2 genotypes were determined by sequencing and restriction enzyme
      analysis, respectively. The number of daily vomits was modeled by a Poisson
      probability mass function. Comparisons of other tolerability measures by
      regimens, gender, and genotypes were evaluated by a linear mixed-effects model.
      The covariate effects associated with efavirenz, gender, and NAT1*3, NAT1*14, and
      NAT2*5 alleles corresponded to 25, 37, -17, -48, and -27% changes, respectively,
      in oral clearance of PAS. The NAT1*10 allele did not influence drug clearance.
      The time above the MIC of 1 mg/liter was significantly different between the two
      regimens but not influenced by the NAT1 or NAT2 genotypes. The occurrence and
      intensity of intolerance differed little between regimens. Four grams of GSR-PAS
      twice daily but not 8 g once daily ensured concentrations exceeding the MIC (1
      mg/liter) throughout the dosing interval; PAS intolerance was not related to
      maximum PAS concentrations over the doses studied and was not more frequent after
      once-daily dosing. We confirm that the slow phenotype conferred by the NAT1*14
      and NAT1*3 alleles resulted in higher PAS exposure but found no evidence of
      increased activity of the NAT1*10 allele.

PMID- 25963986
TI  - Staphylococcus aureus metabolic adaptations during the transition from a
      daptomycin susceptibility phenotype to a daptomycin nonsusceptibility phenotype.
AB  - Staphylococcus aureus is a major cause of nosocomial and community-acquired
      infections. The success of S. aureus as a pathogen is due in part to its many
      virulence determinants and resistance to antimicrobials. In particular,
      methicillin-resistant S. aureus has emerged as a major cause of infections and
      led to increased use of the antibiotics vancomycin and daptomycin, which has
      increased the isolation of vancomycin-intermediate S. aureus and daptomycin
      nonsusceptible S. aureus strains. The most common mechanism by which S. aureus
      acquires intermediate resistance to antibiotics is by adapting its physiology and
      metabolism to permit growth in the presence of these antibiotics, a process known
      as adaptive resistance. To better understand the physiological and metabolic
      changes associated with adaptive resistance, six daptomycin-susceptible and 
      nonsusceptible isogenic strain pairs were examined for changes in growth,
      competitive fitness, and metabolic alterations. Interestingly, daptomycin
      nonsusceptibility coincides with a slightly delayed transition to the
      postexponential growth phase and alterations in metabolism. Specifically,
      daptomycin-nonsusceptible strains have decreased tricarboxylic acid cycle
      activity, which correlates with increased synthesis of pyrimidines and purines
      and increased carbon flow to pathways associated with wall teichoic acid and
      peptidoglycan biosynthesis. Importantly, these data provided an opportunity to
      alter the daptomycin nonsusceptibility phenotype by manipulating bacterial
      metabolism, a first step in developing compounds that target metabolic pathways
      that can be used in combination with daptomycin to reduce treatment failures.

PMID- 25963988
TI  - Altered Micafungin Pharmacokinetics in Intensive Care Unit Patients.
AB  - Micafungin is considered an important agent for the treatment of invasive fungal
      infections in the intensive care unit (ICU). Little is known on the
      pharmacokinetics of micafungin. We investigated micafungin pharmacokinetics (PK)
      in ICU patients and set out to explore the parameters that influence micafungin
      plasma concentrations. ICU patients receiving 100 mg of intravenous micafungin
      once daily for suspected or proven fungal infection or as prophylaxis were
      eligible. Daily trough concentrations and PK curves (days 3 and 7) were
      collected. Pharmacokinetic analysis was performed using a standard two-stage
      approach. Twenty patients from the ICUs of four hospitals were evaluated. On day
      3 (n = 20), the median (interquartile range [IQR]) area under the concentration
      time curve from 0 to 24 h (AUC0-24) was 78.6 (65.3 to 94.1) mg . h/liter, the
      maximum concentration of drug in serum (Cmax) was 7.2 (5.4 to 9.2) mg/liter, the
      concentration 24 h after dosing (C24) was 1.55 (1.4 to 3.1) mg/liter, the volume
      of distribution (V) was 25.6 (21.3 to 29.1) liters, the clearance (CL) was 1.3
      (1.1 to 1.5) liters/h, and the elimination half-life (t1/2) was 13.7 (12.2 to
      15.5) h. The pharmacokinetic parameters on day 7 (n = 12) were not significantly
      different from those on day 3. Daily trough concentrations (day 3 to the end of
      therapy) showed moderate interindividual (57.9%) and limited intraindividual
      variability (12.9%). No covariates of the influence on micafungin exposure were
      identified. Micafungin was considered safe and well tolerated. We performed the
      first PK study with very intensive sampling on multiple occasions in ICU
      patients, which aided in resolving micafungin PK. Strikingly, micafungin exposure
      in our cohort of ICU patients was lower than that in healthy volunteers but not
      significantly different from that of other reference populations. The clinical
      consequence of these findings must be investigated in a pharmacokinetic
      pharmacodynamic (PK-PD) study incorporating outcome in a larger cohort. (This
      study is registered at ClinicalTrials.gov under registration no. NCT01783379.). 

PMID- 25963989
TI  - Tertiary Lymphoid Structures in Rheumatoid Arthritis: NF-kappaB-Inducing Kinase
      Positive Endothelial Cells as Central Players.
AB  - Tertiary lymphoid structures (TLSs) in chronic inflammation, including rheumatoid
      arthritis (RA) synovial tissue (ST), often contain high endothelial venules and
      follicular dendritic cells (FDCs). Endothelial cell (EC)-specific lymphotoxin
      beta (LTbeta) receptor signaling is critical for the formation of lymph nodes and
      high endothelial venules. FDCs arise from perivascular platelet-derived growth
      factor receptor beta(+) precursor cells (preFDCs) that require specific group 3
      innate lymphoid cells (ILC3s) and LTbeta for their expansion. Previously, we
      showed that RA ST contains ECs that express NF-kappaB-inducing kinase (NIK),
      which is pivotal in LTbeta-induced noncanonical NF-kappaB signaling. We studied
      the relation between NIK(+) ECs, (pre)FDCs, and ILC3s with respect to TLSs in RA
      ST. TLS(+) tissues exhibited a significantly increased expression of genes
      involved in noncanonical NF-kappaB signaling, including NIK, and
      immunohistochemical analysis revealed that NIK was almost exclusively expressed
      by ECs. ILC3s were present in human RA ST in very low numbers, but not
      differentially in TLS(+) tissues. In contrast, TLS(+) tissues contained
      significantly more NIK(+) ECs and perivascular platelet-derived growth factor
      receptor beta(+) preFDCs, which correlated significantly with the quantity of
      FDCs. We established a strong link between NIK(+) ECs, (pre)FDCs, and the
      presence of TLSs, indicating that NIK(+) ECs may not only be important
      orchestrators of lymph node development but also contribute to the formation of
      TLSs in chronic inflammation. 

PMID- 25963992
TI  - Cholesterol-induced changes in hippocampal membranes utilizing a phase-sensitive
      fluorescence probe.
AB  - The function of membrane receptors in the nervous system depends on
      physicochemical characteristics of neuronal membranes such as membrane order and
      phase. In this work, we have monitored the changes in hippocampal membrane order
      and related parameters by cholesterol and protein content utilizing a Nile Red
      based phase-sensitive fluorescent membrane probe NR12S. Since alteration of
      membrane cholesterol is often associated with membrane phase change, the phase
      sensitive nature of NR12S fluorescence becomes useful in these experiments. Our
      results show that fluorescence spectroscopic parameters such as emission maximum,
      anisotropy, and lifetime of NR12S display characteristic dependence on membrane
      cholesterol content. Interestingly, cholesterol-dependent red edge excitation
      shift is displayed by NR12S under these conditions. Hippocampal membranes
      exhibited reduction in liquid-ordered phase upon cholesterol depletion. These
      results provide insight into changes in hippocampal membrane order in the overall
      context of cholesterol and protein modulation. 

PMID- 25963993
TI  - Design of new fluorescent cholesterol and ergosterol analogs: Insights from
      theory.
AB  - Cholesterol (Chol) and ergosterol (Erg) are abundant and important sterols in the
      plasma membrane of mammalian and yeast cells, respectively. The effects of Chol
      and Erg on membrane properties, as well as their intracellular transport, can be
      studied with use of fluorescence probes mimicking both sterols as closely as
      possible. In the search for new and efficient Chol and Erg probes, we use a
      combination of theoretical methods to explore a series of analogs. The optical
      properties of the analogs (i.e. excitation energies, emission energies and
      oscillator strengths) are examined using time-dependent density functional theory
      (TDDFT) and their ability to mimic the effects of Chol and Erg on membranes is
      investigated with molecular dynamics (MD) simulations of each analog in a 1
      palmitoyl-2-oleoyl-phosphatidylcholine (POPC) bilayer. From the set of analogs we
      find two probes (3a and 3b) to display favorable electronic transition properties
      as well as strong condensing abilities. These findings can lead to the use of new
      efficient probes and aid in the understanding of the structural features of Chol
      and Erg that impart to them their unique effects on lipid membranes. 

PMID- 25963990
TI  - Discovery and Classification of Fusion Transcripts in Prostate Cancer and Normal
      Prostate Tissue.
AB  - Fusion transcript formation is one of the fundamental mechanisms that drives the
      development of prostate cancer. Because of the advance of high-throughput
      parallel sequencing, many fusion transcripts have been discovered. However, the
      discovery rate of fusion transcripts specific for prostate cancer is lagging
      behind the discoveries made on chromosome abnormalities of prostate cancer.
      Recent analyses suggest that many fusion transcripts are present in both benign
      and cancerous tissues. Some of these fusion transcripts likely represent
      important components of normal gene expression in cells. It is necessary to
      identify the criteria and features of fusion transcripts that are specific for
      cancer. In this review, we discuss optimization of RNA sequencing depth for
      fusion transcript discovery and the characteristics of fusion transcripts in
      normal prostate tissues and prostate cancer. We also propose a new classification
      of cancer-specific fusion transcripts on the basis of their tail gene fusion
      protein product and the roles that these fusions may play in cancer development. 

PMID- 25963994
TI  - Predicting posttraumatic stress disorder in children and parents following
      accidental child injury: evaluation of the Screening Tool for Early Predictors of
      Posttraumatic Stress Disorder (STEPP).
AB  - BACKGROUND: Children and their parents are at risk of posttraumatic stress
      disorder (PTSD) following injury due to pediatric accidental trauma. Screening
      could help predict those at greatest risk and provide an opportunity for
      monitoring so that early intervention may be provided. The purpose of this study
      was to evaluate the Screening Tool for Early Predictors of Posttraumatic Stress
      Disorder (STEPP) in a mixed-trauma sample in a non-English speaking country (the
      Netherlands). METHODS: Children aged 8-18 and one of their parents were recruited
      in two academic level I trauma centers. The STEPP was assessed in 161 children
      (mean age 13.9 years) and 156 parents within one week of the accident. Three
      months later, clinical diagnoses and symptoms of PTSD were assessed in 147
      children and 135 parents. We used the Anxiety Disorders Interview Schedule for
      DSM-IV - Child and Parent version, the Children's Revised Impact of Event Scale
      and the Impact of Event Scale-Revised. Receiver Operating Characteristic analyses
      were performed to estimate the Areas Under the Curve as a measure of performance
      and to determine the optimal cut-off score in our sample. Sensitivity,
      specificity, positive and negative predictive values were calculated. The aim was
      to maximize both sensitivity and negative predictive values. RESULTS: PTSD was
      diagnosed in 12% of the children; 10% of their parents scored above the cut-off
      point for PTSD. At the originally recommended cut-off scores (4 for children, 3
      for parents), the sensitivity in our sample was 41% for children and 54% for
      parents. Negative predictive values were 92% for both groups. Adjusting the cut
      off scores to 2 improved sensitivity to 82% for children and 92% for parents,
      with negative predictive values of 92% and 96%, respectively. CONCLUSIONS: With
      adjusted cut-off scores, the STEPP performed well: 82% of the children and 92% of
      the parents with a subsequent positive diagnosis were identified correctly.
      Special attention in the screening procedure is required because of a high rate
      of false positives. The STEPP appears to be a valid and useful instrument that
      can be used in the Netherlands as a first screening method in stepped
      psychotrauma care following accidents.

PMID- 25963995
TI  - Small non-coding RNAs transfer through mammalian placenta and directly regulate
      fetal gene expression.

PMID- 25963996
TI  - Astrocyte development: A Guide for the Perplexed.
AB  - Astrocytes are the predominant cell type in the brain and perform key functions
      vital to CNS physiology, including blood brain barrier formation and maintenance,
      synaptogenesis, neurotransmission, and metabolic regulation. To fully understand
      the contributions of astrocytes to brain function, it will be important to bridge
      the existing gap between development and physiology. In this review, we provide
      an overview of Astrocyte development, including recent insights into molecular
      mechanisms of astrocyte specification, regional patterning and proliferation.
      This developmental perspective is complemented with recent findings that describe
      the functional maturation of astrocytes and their prospective diversity. Future
      progress in understanding Astrocyte development will depend on the development of
      astrocyte- stage specific markers and tools for manipulating astrocytes without
      affecting neuron production. Ultimately, a mechanistic approach to Astrocyte
      development will be crucial to developing new treatments for the many
      neurodevelopmental, neurodegenerative, neuroimmune, and neoplastic diseases
      involving astrocyte dysfunction.

PMID- 25963997
TI  - Effects of Hemodialysis on Methadone Pharmacokinetics and QTc.
AB  - PURPOSE: Effects of hemodialysis on pharmacokinetic properties and QTc were
      studied in 4 patients taking daily methadone dose of 100 mg (range, 60-120 mg).
      METHODS: Methadone in serum, dialysate, and urine were measured by LC-MS/MS. QTc
      was calculated with Bazett's formula. FINDINGS: The serum Cmin methadone level
      was 1124 nmol/L (range, 547-1581 nmol/L). Methadone dialysate clearance was 17.1
      mL/min (range, 13.7-20.6 mL/min). Total loss in dialysate was 2.30% (range, 1,25
      3,70%) of daily methadone intake. QTc increased from 391 msec (range, 369-406
      msec) to 445 msec (range, 407-479 msec), independently of serum methadone level,
      which may be explained by normalization of serum electrolytes. IMPLICATIONS:
      Methadone dose adjustment is not needed because of hemodialysis.

PMID- 25963998
TI  - Use of Pharmacogenomics and Biomarkers in the Development of New Drugs for
      Alzheimer Disease in Japan.
AB  - PURPOSE: Pharmacogenomics (PGx) and biomarkers have been utilized for improving
      the benefit/risk ratios of drugs and the efficiency of drug development. In the
      development of drugs for Alzheimer disease (AD), a number of clinical trials have
      failed to demonstrate clinical efficacy. To overcome this circumstance, the
      importance of using PGx/biomarkers for enhancing recruitment into clinical trials
      and for evaluating the efficacy of treatments has been increasingly recognized.
      In this article, the current status and examples of the use of PGx/biomarkers in
      Japan for drug development are explained. METHODS: Guidelines, notifications, and
      administrative notices related to PGx/biomarkers were downloaded from the Web
      sites of the Pharmaceuticals and Medical Devices Agency (PMDA), the US Food and
      Drug Administration, and the European Medicines Agency. Data from clinical
      studies of AD drugs were obtained from the review reports of the PMDA. To analyze
      the current status of the use of PGx/biomarkers in Japan, "Issues to Consider in
      the Clinical Evaluation and Development of Drugs for Alzheimer's Disease (Interim
      Summary)" was also downloaded from PMDA Web site. FINDINGS: There are 2 major
      measures of utilizing PGx/biomarkers for drug development: (1) biomarker
      qualification and (2) companion diagnostics. Recently, the PMDA issued a number
      of guidelines and notifications for their practical use. Although examples of
      qualified PGx/biomarkers and approved companion diagnostics are limited at
      present, it is expected that the use of PGx/biomarkers for the development of
      drugs against AD would increase. IMPLICATIONS: For promoting the use of
      PGx/biomarkers in the development of drugs against AD, PGx/biomarkers should be
      qualified as early as possible. To that end, accumulating data on PGx/biomarkers
      from nonclinical or clinical trials and the concurrent development of reliable
      diagnostics in the early stage of the development process are indispensable. It
      is important to strengthen collaboration among the academia, industries, and
      regulatory agencies, followed by the establishment of an effective guideline in
      the area of AD.

PMID- 25963999
TI  - Prevalence of musculoskeletal symptoms in the five urban regions of Brazil-the
      Brazilian COPCORD study (BRAZCO).
AB  - The objective of this study is to describe the prevalence of musculoskeletal
      symptoms (MSK-S) in the five urban geographical regions of Brazil using the
      Portuguese version of the Community Oriented Program for Control of Rheumatic
      Diseases (COPCORD) core questionnaire (CQ)-BRAZCO study. From April to May 2013,
      a population-based survey was conducted by applying the CQ for 5000 individuals
      aged over 15 years in 16 capitals of the Brazilian regions. Trained teams
      assessed the MSK-S and socioeconomic status. The sample consisted of
      representative quotas of the Brazilian population, proportional to the capitals'
      population density. It respected the groups' quotas of gender and age and
      included all socioeconomic classes, educational levels, and occupations. There
      were 1342 (26.9 %) participants who presented MSK-S unrelated to trauma in 7 days
      preceding the interview. A higher prevalence of these complaints were in females
      (65.2 %), elderly people, in the north region of the country (30.7 %), and a
      lower prevalence was found in single individuals (41.7 %) and in the south (23.3
      %). The most frequent pain sites were the spine (76.7 %) and knees (49.6 %), and
      the mean pain intensity was 6.8 (VAS). The BRAZCO study shows that Brazilian
      population presents a higher rate of MSK-S unrelated to trauma than many Asian
      countries. These results can be applied to guide the assessment of prevalence of
      rheumatic diseases. Additionally, it can help in the design of policies for
      health care workforce organization and its accessibility, as well as to reduce
      the risk of rheumatic diseases at the community level. 

PMID- 25964000
TI  - Stress-hemoconcentration: plasma volume changes or splenic contraction? A Reply
      to Engan and Schagatay.

PMID- 25964002
TI  - Assessing cognition after stroke. Who misses out? A systematic review.
AB  - BACKGROUND: Cognitive impairments post-stroke are common. Assessment of cognition
      typically involves pen-and-paper tasks, which are often reliant on linguistic and
      motor function, creating barriers for many stroke survivors. The characteristics
      of stroke survivors excluded from cognitive assessments have never been
      investigated. AIMS: (1) To determine if the stroke samples included in studies
      evaluating clinimetric properties of cognitive assessments represent the stroke
      population, (2) to identify the different modes of cognitive assessments, and (3)
      to ascertain whether the different modes of cognitive assessments influence the
      stroke samples used in the studies. SUMMARY OF REVIEW: We systematically reviewed
      studies that evaluated at least one clinimetric property of a cognitive
      assessment in adult stroke survivors from January 2000 to October 2013.
      Eligibility criteria, reasons for drop-outs and missing data were extracted. A
      theming process was employed to synthesize the data. From the initial yield of
      3731 articles, 109 were included. Six broad categories describing reasons for
      exclusion were identified. Cognitive impairments were the most common (68%), then
      communication issues (62%), endurance problems (42%), sensory loss (39%),
      psychiatric illness (38%) and motor limitations (27%). The most prevalent
      assessment mode was pen-and-paper (73%), then virtual reality (11%), computer
      (6%), observational functional performance (5%), informant (3%) and telephone
      (3%). Regardless of mode, issues with cognition and communication were the most
      frequently used exclusion criteria. CONCLUSIONS: Our findings indicate that
      cognitive assessments are not tested in representative stroke samples. Research
      is needed to identify valid and reliable cognitive assessments that are feasible
      in a wider range of stroke survivors.

PMID- 25964001
TI  - It's Complicated: Marital Ambivalence on Ambulatory Blood Pressure and Daily
      Interpersonal Functioning.
AB  - BACKGROUND: Marriage decreases cardiovascular morbidity although relationship
      quality matters. While some marriages contain highly positive aspects
      (supportive), marriages may also simultaneously contain both positive and
      negative aspects (ambivalent). Individuals whose spouses or own behavior is
      ambivalent may not experience the same cardiovascular-protective benefits of
      marriage. PURPOSE: The purpose of this study is to elucidate the physiological
      pathways by which marital quality may influence long-term health and examine
      ambivalent behavior on interpersonal-functioning and ambulatory blood pressure
      (ABP). METHODS: Interpersonal functioning and ABP were examined in 94 couples.
      RESULTS: Spousal and own ambivalent behavior was associated with lower intimacy
      (ps < .01) and higher systolic ABP (ps < .01). Spousal ambivalent behavior was
      associated with lower ratings of partner responsiveness (p < .01) and less self-
      and spousal-disclosure (ps < .05). Mediational analyses indicated that own
      behavior mediated links between spousal ambivalent behavior and ABP. CONCLUSIONS:
      Despite the positivity in relationships, individuals whose spouses' or own
      behavior is ambivalent may not receive cardiovascular protection from this
      positivity.

PMID- 25964003
TI  - Borazine: spin blocker or not?
AB  - The spin blocker capacity of borazine is investigated. Specifically, meta-B-B,
      meta-N-N and para-B-N connected borazines are used as spin-blocker couplers
      comprised of a pair of radicals: two iminonitroxides (IN); IN and
      tetrathiafulvalene radical cations (TTF); or two TTFs. Density functional theory
      (DFT) is used to elucidate the spin blocker capacity of the linkage-specific
      (meta or para) borazine-coupler and elaborate the role of the lowest unoccupied
      molecular orbital (LUMO) in magnetic-exchange. Furthermore, a qualitative
      relation between different magnetic aromaticity indices is made using both
      nuclear-independent chemical shift (NICS) and the harmonic oscillator model of
      aromaticity (HOMA). The NICS values are calculated at the centre of the borazine
      spacer fragment of these diradical species and then also at 0.5 A increments of
      the virtual probe from this centre position up to an orthogonal distance of 2.0 A
      from the centre. The HOMA values are calculated for the borazine ring fragment in
      these diradicals. Based on the HOMA and NICS values, it is evident that the
      borazine exhibits less aromatic character than benzene itself - due to the polar
      nature of B-N pi-bonding. The LUMO mediated spin-exchange between the two
      consecutive singly occupied molecular orbitals (SOMOs) is explicitly discussed
      and confirmed to play a pivotal role. The parity of the coupler pathways, i.e.
      even or odd number of bonds along a selected pathway, between radical moieties is
      an important factor in predicting the nature and extent of magnetic exchange for
      these diradicals. Surprisingly, borazine does not always act as a spin-coupling
      blocker - rather in some cases the coupling is enhanced as compared to a
      homoatomic (carbon-based) benzene coupler. 

PMID- 25964004
TI  - Overgrowth of costochondral grafts in craniomaxillofacial reconstruction: Rare
      complication and literature review.
AB  - OBJECTIVE: Costochondral grafts (CCGs) have been used for the reconstruction of
      the craniomaxillofacial defects in various situations. However, there is
      controversy concerning the growth pattern of CCGs, which is often unpredictable
      and may manifest as overgrowth or no growth at all. This article summarizes the
      literature concerning overgrowth of CCGs in craniomaxillofacial reconstruction,
      and presents an uncommon case of treatment for overgrowth of costal graft in
      mandibular body reconstruction. MATERIAL AND METHODS: The literature on
      overgrowth of CCGs in craniomaxillofacial reconstruction was reviewed with a
      chart. A 25-year-old man received mandibular partial resection because of
      adamantoblastoma, followed by replacement of costal graft. Two years
      postoperatively, he began to present with facial asymmetry and malocclusion.
      Clinical and radiologic image examination showed deviation of the chin to the
      left side, and overgrowth of the costal graft was diagnosed. Left sagittal split
      ramus osteotomy (SSRO), genioplasty, and left mandibular angle ostectomy (MAO)
      were performed. RESULTS: A total of 30 articles containing 68 cases of overgrowth
      of CCGs in craniomaxillofacial reconstructions have been reported since 1977,
      including the present case. During a 2-year follow-up, the patient's
      postoperative facial profile and contour appeared stable clinically and
      radiographically, and an improved symmetry facial contour and occlusion were
      achieved. CONCLUSION: The growth of CCGs may be influenced by complex factors
      such as the function of the mandible, inherent growth capacity, and possibly
      hormonal factors. Once overgrowth of the costal graft occurs in mandibular body
      reconstruction, SSRO combined with genioplasty and MAO could be the optimal
      option to restore a symmetrical face.

PMID- 25964005
TI  - The validity of surgical clips as radiographic markers for the tumour resection
      cavity in head and neck cancer treatment.
AB  - BACKGROUND: A prerequisite of irradiation after advanced head and neck tumour
      resection is the accurate localization of the tumour resection margin. The
      purpose of the following study is to evaluate the use of surgical clips placed in
      the tumour resection margins for use as radiographic markers to facilitate
      focussed adjuvant radiation therapy. MATERIALS: To evaluate whether the clips
      remain predictive for the resection margin, we analysed the deviation of each
      clip in two postoperative CT scans on different days. Bone registration points
      were used to fuse the two CT scans in the region of the primary tumour and the
      distances between corresponding clips were measured. RESULTS: The tumour
      resection margins were labelled with an average of 18 titanium clips. In total
      282 clips were evaluated. Metric analysis of clip deviation between the two
      postoperative CT scans found a mean distance of 4.5 mm +/- 2.5 mm with a range of
      0.5-11.8 mm. No significant statistical relationship of the clip differences as a
      function of time, the method of reconstruction or administered radiotherapy could
      be demonstrated. CONCLUSION: Placement of surgical clips in the cavity walls
      after complete tumour resection provides an easy and inexpensive approach for
      defining resection margins and allows for increased accuracy of adjuvant
      treatment. Clinical trial number DRKS00007534.

PMID- 25964006
TI  - Long-term retrospective evaluation of the peri-implant bone level in onlay
      grafted patients with iliac bone from the anterior superior iliac crest.
AB  - OBJECTIVE: The purpose of the present study was to evaluate crestal bone level
      changes around dental implants after iliac bone augmentation in the long term.
      MATERIAL AND METHODS: A total of 32 partially edentulous/edentulous patients
      (mean age, 52 years; range, 22-70 years) and a remaining bone volume of less than
      5 mm of the alveolar ridge underwent maxillary or mandibular iliac bone graft
      augmentation. All patients received spaced standardized radiological examination
      for evaluation of peri-implant crestal bone loss. RESULTS: The grafting procedure
      was successfully performed in all patients. A total of 150 implants were placed.
      The mean observation period was 69 months (range, 12-165 months; success rate for
      maxilla, 96%; success rate for mandible, 92%). The mean amount of crestal bone
      loss after 10 years was 1.8 mm. A significant difference between gender and
      crestal bone loss was shown, but no influence was found regarding the implant
      system, diameter of implant, and age of the patients. CONCLUSION: In patients
      with atrophic jaws, a sufficient long-term reconstruction can be achieved with
      the combination of iliac onlay grafting and dental implants. The results
      demonstrate high success rates and a stable peri-implant bone level in the long
      term.

PMID- 25964007
TI  - Gender trends in authorship in oral and maxillofacial surgery literature: A 30
      year analysis.
AB  - The aim of the present study was to perform a bibliometric analysis of the gender
      distribution of first and senior authorships in important oral and maxillofacial
      journals over the 30-year period from 1980 to 2010. Articles published in three
      representative oral and maxillofacial surgery journals were selected. The years
      1980, 1990, 2000, and 2010 were chosen as representative points in time for
      article selection. Original research, case reports, technical notes, and reviews
      were included in the analysis. Case reports and technical notes were pooled in
      one group. For each article, the gender of the first author as well as that of
      the senior author was determined, based on the inspection of their first name.
      The type of article was determined and the country of origin of the article was
      documented. A total 1412 articles were subjected to the data analysis. A
      significant increase in female authorship in oral and maxillofacial surgery could
      be identified over the chosen 30-year period. However, the number of publications
      by male authors was still significantly higher at all points of time, exceeding
      those of female authors by at least 3.8 fold in 2010. As there is a trend towards
      feminization of medicine and dentistry, the results of the present study may
      serve as the basis for further analysis of the current situation, and the
      identification of necessary actions to accelerate the closure of the gender gap
      in publishing in oral and maxillofacial surgery. 

PMID- 25964008
TI  - A systematic review and comparison of functional assessments of community
      dwelling elderly patients.
AB  - PURPOSE: To provide advanced practice nurses in primary care with information
      about self-reported functional assessments and physical performance-based
      functional assessments of geriatric patients living alone within the community at
      greatest risk of functional decline. DATA SOURCES: Databases searched include
      CINAHL, Healthsource: Nursing/Academic Edition, MEDLINE, PsycINFO, PsycARTICLES,
      Cochrane Library, and National Clearinghouse Guidelines. The review was limited
      to English, research, and the years 2000-2014. Key search words included
      geriatric, community-dwelling, functional assessment, activities and instrumental
      activities of daily living, Barthel Index, Katz Index, Lawton Scale, Vulnerable
      Elders Survey, Timed Up and Go Test, Gait Speed Test, Functional Reach Test, and
      primary care. CONCLUSIONS: Forty-three million individuals, age 65 and older, are
      currently living in the United States with numbers expected to double by 2050.
      Nurse practitioners will be at the forefront of assessing for functional decline
      and can use tools such as the Barthel Index and Gait Speed Test to improve
      elderly outcomes. IMPLICATIONS FOR PRACTICE: Self-reported functional
      questionnaires and physical functional performance tests can quickly be completed
      in the office to track the risk of functional decline over time. Interventions,
      such as physical therapy or other community resources, can be initiated when
      needed to reduce negative outcomes of functional decline.

PMID- 25964009
TI  - Optical coherence tomography assessment of the mechanistic effects of rotational
      and orbital atherectomy in severely calcified coronary lesions.
AB  - OBJECTIVES: This study sought to assess the mechanistic effect of rotational
      atherectomy (RA) and orbital atherectomy (OA) on heavily calcified coronary
      lesions and subsequent stent placement using optical coherence tomography (OCT).
      BACKGROUND: RA and OA are two main approaches to ablate coronary calcium. While
      small case reports have described the mechanistic effect of RA in calcified
      coronary lesions, there has been no imaging study to assess the effect of OA on
      coronary artery architecture and/or compare the effects of two atherectomy
      devices. METHODS: This study analyzed 20 consecutive patients with OCT imaging
      performed after atherectomy and after stent implantation, RA (n = 10) and OA (n =
      10). RESULTS: Postatherectomy OCT analysis identified tissue modification with
      deep dissections in around a third of lesions after RA and OA; however, post OA
      dissections ("lacunae") were significantly deeper (1.14 vs. 0.82 mm, P = 0.048).
      Post OA/RA lesions with dissections had significantly higher percentage of lipid
      rich plaques and smaller calcification arcs as compared to plaques without
      dissections. Stents after OA were associated with a significantly lower percent
      of stent strut malapposition than post RA stents (4.36 vs. 8.02%, P = 0.038).
      CONCLUSIONS: Although the incidence of dissections was comparable between RA and
      OA cases, OA resulted in deeper tissue modifications (lacunae) as shown by OCT
      imaging. The finding might provide an explanation for a better stent apposition
      after OA as compared to RA. Their impact on long-term outcome needs to be
      determined.

PMID- 25964010
TI  - Arginine kinases from the marine feather star Tropiometra afra macrodiscus: The
      first finding of a prenylation signal sequence in metazoan phosphagen kinases.
AB  - Two arginine kinase cDNAs (AK1 and AK2) were isolated from the marine feather
      star Tropiometra afra macrodiscus, and the gene structure (exon/intron
      organization) of AK1 was determined. The cDNA-derived amino acid sequences and
      the exon/intron organization of the Tropiometra AK1 gene were homologous to those
      of a human creatine kinase (CK) as well as the AK of the sea cucumber Stichopus.
      Phylogenetic analysis also supports the close relationship between human CKs and
      echinoderm AKs, indicating that the latter AKs evolved from an ancestral CK gene.
      We observed that the Tropiometra AK1 gene has a novel C-terminal extension
      (approximately 50 amino acid residues) encoded by a unique exon. Moreover, a
      typical prenylation signal sequence (CSLL) was found at the C-terminal end of
      this extension, suggesting that AK1 is anchored to a membrane. AK2 had no such C
      terminal extension. This is the first finding of a prenylation signal in metazoan
      phosphagen kinases. Recombinant Tropiometra AK1 and AK2 enzymes were successfully
      expressed in Escherichia coli, and their kinetic constants were determined. Both
      enzymes showed activity comparable to that of typical invertebrate AKs. 

PMID- 25964011
TI  - Low Abundant N-linked Glycosylation in Hen Egg White Lysozyme Is Localized at
      Nonconsensus Sites.
AB  - Although wild-type hen egg white lysozyme (HEL) is lacking the consensus sequence
      motif NX(S/T), in 1995 Trudel et al. (Biochem. Cell Biol. 1995, 73, 307-309)
      proposed the existence of a low abundant N-glycosylated form of HEL; however, the
      identity of active glycosylation sites in HEL remained a matter of speculation.
      For the first time since Trudel's initial work, we report here a comprehensive
      characterization by means of mass spectrometry of N-glycosylation in wild-type
      HEL. Our analytical approach comprised ZIC-HILIC enrichment of N-glycopeptides
      from HEL trypsin digest, deglycosylation by (18)O/PNGase F as well as by various
      endoglycosidases, and LC-MS/MS analysis of both intact and deglycosylated N
      glycopeptides engaging multiple techniques of ionization and fragmentation. A
      novel data interpretation workflow based on MS/MS spectra classification and
      glycan database searching enabled the straightforward identification of the
      asparagine-rich N-glycopeptide [34-45] FESNFNTQATNR and allowed for compositional
      profiling of its modifying N-glycans. The overall heterogeneity profile of N
      glycans in HEL comprised at least 26 different compositions. Results obtained
      from deglycosylation experiments provided clear evidence of asparagine residues
      N44 and N39 representing active glycosylation sites in HEL. Both of these sites
      do not fall into any known N-glycosylation-specific sequence motif but are
      localized in rarely observed nonconsensus sequons (NXN, NXQ). 

PMID- 25964012
TI  - Climate variability modulates western US ozone air quality in spring via deep
      stratospheric intrusions.
AB  - Evidence suggests deep stratospheric intrusions can elevate western US surface
      ozone to unhealthy levels during spring. These intrusions can be classified as
      'exceptional events', which are not counted towards non-attainment
      determinations. Understanding the factors driving the year-to-year variability of
      these intrusions is thus relevant for effective implementation of the US ozone
      air quality standard. Here we use observations and model simulations to link
      these events to modes of climate variability. We show more frequent late spring
      stratospheric intrusions when the polar jet meanders towards the western United
      States, such as occurs following strong La Nina winters (Nino3.4<-1.0  degrees
      C). While El Nino leads to enhancements of upper tropospheric ozone, we find this
      influence does not reach surface air. Fewer and weaker intrusion events follow in
      the two springs after the 1991 volcanic eruption of Mt. Pinatubo. The linkage
      between La Nina and western US stratospheric intrusions can be exploited to
      provide a few months of lead time during which preparations could be made to
      deploy targeted measurements aimed at identifying these exceptional events. 

PMID- 25964013
TI  - Predictors of regular exercise among older residents of long-term care
      institutions.
AB  - The purpose of this study was to apply self-efficacy theory to explore predictors
      of regular exercise among older residents of long-term care institutions.
      Convenience sampling was used to collect data from 151 older adults residing in
      three residential care homes in Taiwan. Data collection instruments included a
      background data sheet, Self Efficacy for Exercise Scale, Outcome Expectations for
      Exercise Scale and self-reported regular exercise. Results indicated that older
      residents who exercised regularly had fewer chronic diseases, better perceived
      health status and functional status, and higher self-efficacy expectations and
      outcome expectations related to exercise. Older residents with a regular exercise
      habit prior to institutionalization were more likely to engage in regular
      exercise. Logistic regression analysis indicated past exercise participation and
      self-efficacy expectations to be significant positive predictors of regular
      exercise. To promote regular exercise within this population, these can be
      potential target areas for interventions. These factors should be targeted in the
      development and implementation of interventions to promote regular exercise among
      older residents of long-term care institutions. 

PMID- 25964014
TI  - Establishing an Early Discharge Protocol After Cardiac Surgery in Korea.
AB  - This column shares the best evidence-based strategies and innovative ideas on how
      to facilitate the learning of EBP principles and processes by clinicians as well
      as nursing and interprofessional students. Guidelines for submission are
      available at http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1741-6787. 

PMID- 25964018
TI  - Expert opinion of Spanish rheumatologists about the role of physical exercise in
      ankging spondylitis and other rheumatic diseases.
AB  - OBJECTIVE: To analyze the perceptions of Spanish rheumatologists, experts in
      spondyloarthropathies (SpA), on the role of exercise in these and in other
      rheumatic diseases METHODS: A survey to 106 rheumatologists belonging to an SpA
      working group of the Spanish Society of Rheumatology, GRESSER, was collected. The
      questions were related with general aspects of professional exercise (clinical
      practice and generic knowledge), use of fitness in SpA (benefits, indications,
      contraindications, compliance, facilitators), sociodemographic characteristics
      and professional experience with the respondents' exercise regimen. A descriptive
      analysis was performed. RESULTS: the survey was sent to 106 rheumatologists, 44
      of them answered (51% female, over 20 years of experience). Over 86% believe that
      their patients need exercise, but the prescription is moderate. 42% believe they
      do not have training to prescribe specific exercises. The physical activity
      education materials available consisted essentially of brochures (90%), websites
      (52%) and videos (23%). The therapeutic importance of exercise depends on the
      type of underlying disease. Most agree in decreasing the intensity of exercise
      during disease flares. For most cases of Spa, exercise is not a trigger of flares
      (66%), and may be used at any stage of the disease, depending on the type and the
      phase of the Spa. CONCLUSIONS: Rheumatologists consider exercise as a fundamental
      part of the treatment of rheumatic patients, but greater knowledge and
      development of specific strategies in its prescription is required.

PMID- 25964019
TI  - [Anatomy of the acromioclavicular and coracoclavicular region. Functional and
      clinical aspects].
AB  - BACKGROUND: The acromioclavicular (AC) joint connects the acromion with the
      lateral end of the clavicle and constitutes an important load-transmitting
      element between the upper extremity and the skeleton of the trunk. AIM: This
      review discusses functional aspects that relate the AC and the coracoclavicular
      (CC) ligaments to AC joint instability and lateral clavicle fracture. RESULTS: In
      terms of stability the AC and CC ligaments play a pivotal role for this region.
      Under normal conditions the restraint system is balanced and becomes unbalanced
      in cases of injury such as AC joint instability or lateral clavicular fractures.
      Skeletal injuries frequently affect the ligaments with their usually sharp-angled
      insertion sites, which alters the function of the restraint system. As a
      consequence these injuries lead to multidirectional dislocating forces acting on
      the scapula in relationship to the lateral end of the clavicle. Previously,
      special attention was given to the vertical dislocation of the lateral clavicle,
      whereas less attention was paid to other factors which could lead to dislocation
      in other directions. Therefore, in this review emphasis is placed on the
      anatomical principles of multidirectional dislocation of the AC joint the
      fractured lateral clavicle. CONCLUSION: Current clinical classification schemes
      fail to sufficiently include these multidirectional dislocating forces; however,
      they have to be considered when choosing the appropriate treatment modality.
      Thus, understanding the anatomical and functional context of the AC/CC region is
      essential for a sound management of AC joint injuries and fractures of the distal
      clavicle.

PMID- 25964020
TI  - [Arthroscopically assisted techniques for treatment of acute and chronic
      acromioclavicular joint injuries].
AB  - Acute and chronic acromioclavicular (AC) joint dislocation is frequently
      encountered in the routine clinical practice. This injury can lead to significant
      impairment of shoulder girdle function. Therapy based on the severity of injury
      is recommended to re-establish correct shoulder function. The static radiographic
      Rockwood classification is used to define the degree of dislocation but the
      clinical aspects and functional x-ray imaging of horizontal AC joint instability
      should also be considered for selection of the appropriate procedure. Rockwood
      grades I and II injuries are treated non-operatively with early functional
      exercise. The approach for Rockwood grade III injuries should be individual and
      patient-specific, with non-surgical procedures for low functional requirement
      patients with a high risk for surgical interventions. For patients with high
      demands on shoulder function surgery is recommended. A detailed diagnostic
      assessment frequently reveals Rockwood grade III injuries to be type IV injuries.
      Rockwood types IV and V AC joint dislocations require surgery for sustained
      stability. Treatment of acute injuries is recommended within 1-3 weeks after
      trauma but there is no clear evidence of a cut-off for the presence of chronic
      injuries. Various surgical techniques have been described in the literature. This
      article presents an arthroscopically assisted technique that addresses both
      vertical and horizontal instability of the AC joint. 

PMID- 25964021
TI  - [Therapy of acute acromioclavicular joint instability. Meta-analysis of
      arthroscopic/minimally invasive versus open procedures].
AB  - BACKGROUND: A variety of surgical procedure are desrcibed for the treatment of
      acute acromioclavicular (AC-) joint injuries. Beside open techniques arthroscopic
      assisted procedures spread widely. Each surgical technique offers advantages and
      disadvantages, but none is currently accepted as a gold standard. Therefore, the
      study aims to review the evidence for arthroscopic and open surgical procedures
      in the treatment of acute AC joint instabilities. MATERIAL AND METHODS: According
      to the Cochrane Handbook for Systematic Reviews of Interventions we conducted a
      defined search of Medline and Embase database for articles publisher over the
      last ten years. RESULTS: The search resulted in 961 studies of which 32 were
      included in this review and 3 studies were suitable for a meta-analysis. The
      functional outcome (Constant score) showed a tendency towards better results
      after arthroscopic procedures (weighted mean difference 5.60, 95% confidence
      interval 0.36-10.64). There were no significant differences with respect to
      complication rates, secondary dislocation in the vertical plane, revision surgery
      and AC joint instability. CONCLUSION: There is insufficient evidence to inform
      the surgical management of acute AC joint instability. Due to inconsistent study
      designs there is no evidence for a general superiority of any of the open or
      arthroscopic procedures. Randomized, controlled studies are necessary to
      demonstrate whether arthroscopic techniques show a potential benefit in terms of
      a better functional outcome.

PMID- 25964022
TI  - [Combined ac joint dislocation and distal clavicle fracture. Closed reduction and
      arthroscopically assisted coracoclavicular fixation].
AB  - BACKGROUND: A 55-year-old male patient sustained a dislocation of the
      acromioclavicular (AC) joint in combination with a distal clavicle fracture.
      METHODS: Following closed reduction of the fractured clavicle, arthroscopically
      assisted coracoclavicular fixation was performed. DISCUSSION AND CONCLUSION: A
      combined injury of a complete ac joint dislocation and a distal clavicle fracture
      is rare and is not included in currently available classification systems;
      therefore, in this article a classification and assessment of the stability of
      this injury as well as appropriate treatment options are discussed.

PMID- 25964024
TI  - CE-MS-based serum fingerprinting to track evolution of type 2 diabetes mellitus.
AB  - Development of type 2 diabetes mellitus (T2DM) is preceded by insulin resistance
      (IR), which may evolve to impaired fasting glucose (IFG) and/or impaired glucose
      tolerance (IGT). IFG and IGT are considered as prediabetic states (PD).
      Prediabetes indicates the high risk for the future development of diabetes, it is
      estimated that up to 70% of prediabetics eventually develop T2DM. The risk of
      T2DM development is increased in overweight (OW) and obese (OB) people; however
      normal weight (NW) individuals also suffer from T2DM. The present study was
      designed to evaluate whether changes in polar metabolites induced by T2DM
      evolution are different between NW, overweight and obese individuals. CE-MS serum
      fingerprinting was performed on 197 serum samples obtained from OW, OB, and NW
      humans whom were IR, prediabetics, diabetics or with normal glucose homeostasis.
      Metabolic changes evoked by the progression of T2DM differ between obese,
      overweight, and normal weight subjects. Based on obtained results several
      metabolites can be proposed as a promising target to track T2DM evolution; BCAA
      in OW and NW humans, lysine in OB, while acetylcarnitine and methionine
      independently on body mass index. Validation of obtained results on larger
      population is required.

PMID- 25964023
TI  - [Pertrochanteric femoral fractures in the elderly].
AB  - Pertrochanteric fractures are one of the most common injuries in the elderly and
      due to the demographic changes the incidence and importance of this fracture
      entity will even increase in the future. The dynamic hip screw (DHS) has been
      used as the gold standard implant in the treatment of pertrochanteric femoral
      fractures for many years but recent studies have shown that cephalomedullary
      nails have some advantages. Due to the high incidence, operative treatment of
      these fractures is part of the standard repertoire of trauma surgeons and this
      article therefore provides an overview of existing knowledge and new trends in
      the treatment of pertrochanteric femoral fractures. 

PMID- 25964025
TI  - A Longitudinal Outcome Evaluation of a Prison-Based Sex Offender Treatment
      Program.
AB  - Sex offender outcome studies continue to produce mixed results. A common critique
      of these studies is their lack of methodological rigor. This study attempts to
      address this critique by adhering to the standards established by the
      Collaborative Outcome Data Committee (CODC) aimed at increasing the quality and
      confidence in outcome studies. We examined recidivism outcomes for a sample of
      formerly incarcerated sex offenders who participated in a state prison-based
      cognitive-behavioral-skills-based treatment program. We used propensity score
      analysis to compare treatment participants with a matched sample of non
      participants. The final sample post-matching ( n = 512) was observed for a
      minimum of 4 years and a maximum of 14 years. Using survival analysis, findings
      indicate that there were no differences in recidivism rates between treatment
      participants and non-participants in sexual or violent crimes. However,
      participants demonstrated significantly lower rates of recidivism for non-violent
      crimes. We discuss strengths, limitations of the study, and implications of these
      findings.

PMID- 25964026
TI  - High-resolution MRI using orbit surface coils for the evaluation of metastatic
      risk factors in 143 children with retinoblastoma: Part 2: new vs. old imaging
      concept.
AB  - INTRODUCTION: High-resolution magnetic resonance imaging (MRI) is recommended for
      the evaluation of metastatic risk factors in children with retinoblastoma
      according to recent guidelines. The aim of this study was to compare diagnostic
      accuracy of a new imaging concept with two orbit surface coils to that of an old
      imaging concept with one orbit surface coil. METHODS: One hundred forty-three
      patients (148 eyes, 64 girls, 79 boys) underwent high-resolution MRI on 1.5 T
      scanners using orbit surface coils. The old imaging concept (one orbit surface
      coil focusing on the (most) effected eye additionally to the standard head coil)
      was used in 100 patients/103 eye; the new imaging concept (two orbit surface
      coils (each focusing on one eye) additionally to the standard head coil) in 43
      patients/45 eyes. Image analysis was performed by two neuroradiologists in
      consensus. Histopathology served as gold standard. RESULTS: Detection rate for
      choroidal invasion was higher for the new compared to that for the old imaging
      concept (sensitivity/specificity 87.5/94.6 % vs. 57.1/96.1 % for choroidal
      invasion and 100/97.5 % vs. 58.3/97.7 % for massive choroidal invasion,
      respectively). Sensitivity and specificity for the detection of postlaminar optic
      nerve infiltration, peribulbar fat, and scleral invasion were comparable in both
      imaging concepts; however positive predictive value was higher in the new imaging
      concept (new vs. old imaging concept: 60 vs. 31.6 % for postlaminar and deep
      postlaminar optic nerve infiltration, respectively, and 100 vs. 66.7 % for
      scleral invasion). CONCLUSION: The new imaging concept shows a trend towards
      improving the accuracy of detecting metastatic risk factors in children with
      retinoblastoma and is therefore recommended for pretherapeutic imaging and follow
      up.

PMID- 25964027
TI  - Extensive regeneration of the stomach using bioabsorbable polymer sheets.
AB  - BACKGROUND: The growing prevalence of endoscopic surgery in recent years has led
      to the minimization of postoperative scarring. However, this procedure does not
      allow for the regeneration of the resected digestive tract, which compromises the
      postoperative maintenance of digestive function. In this preliminary study, we
      developed an artificial gastric wall (AGW) using bioabsorbable polymer (BAP), and
      evaluated the ability of this BAP patch to repair and regenerate a widely
      defective gastric wall in an animal model. METHODS: Pigs were laparotomized under
      general anesthesia. An 8 * 8-cm, round portion of the anterior gastric wall was
      excised and replaced by an AGW. The AGW was composed of a copolymer comprising
      50% lactic acid and 50% caprolactone. The animals were relaparotomized 4, 8, or
      12 weeks after implantation, after which they underwent resection of the entire
      stomach for gross and histologic evaluation of the graft sites. RESULTS: All
      recipient pigs survived until killing. By 4-8 weeks, the graft site revealed
      progressively fewer mucosal defect after each day. Moreover, the grafted area was
      indistinguishable from the native stomach 12 weeks after AGW implantation. The
      structures of the regenerated mucous membrane and muscle layers were identical to
      those of the native stomach. Furthermore, proton pumps were found in the
      regenerated tissue. CONCLUSION: The BAP sheets helped to restore extensive
      gastric defects without causing any deformation. The use of BAP sheets may become
      a new therapeutic method that prevents alterations of gastric volume after
      extensive gastrectomy for stomach cancer and other diseases.

PMID- 25964028
TI  - Phase I dose escalation trial of nitroglycerin in addition to 5-fluorouracil and
      radiation therapy for neoadjuvant treatment of operable rectal cancer.
AB  - BACKGROUND: Nitric oxide donors decreased cell survival in vitro and tumor load
      in vivo in models of rectal cancer subjected to ionizing radiation. Nitroglycerin
      (NTG) transdermal patches, added to chemotherapy, have been shown to improve
      outcomes in lung cancer patients. METHODS: This open-label, nonrandomized,
      multicohort, dose escalation, phase I trial had a primary endpoint to evaluate
      the safety, tolerability, feasibility, dose-limiting toxicity and maximum
      tolerated dose of topical NTG in addition to 5-fluorouracil and radiation therapy
      for neoadjuvant treatment of locoregionally advanced operable rectal cancer. The
      secondary endpoint was rate of pathologic complete response (pCR). Patients were
      assigned to 3 sequential cohorts of escalating dose levels of commercially
      available NTG patches (0.2, 0.4, and 0.6 mg/h), each cohort was intended to
      consist of 3 patients. RESULTS: Thirteen patients were enrolled in the trial as
      specified in the dose escalation protocol. They were all male with a median age
      of 59.4 +/- 2.5 (SEM) years. The observed toxicities were mild to moderate and
      manageable. Four patients developed asymptomatic grade 3 lymphopenia during the
      chemoradiation that resolved promptly upon completion. One patient had a non-ST
      segment elevation MI and 1 patient developed diarrhea. None of these toxicities
      were attributed to NTG except for 1 patient who developed a grade 3 headache.
      This required an additional group of patients at the same dose and no other
      patient experienced headaches. pCR was 17%. CONCLUSION: NTG patches are well
      tolerated and it is feasible to proceed with a phase II trial at the maximum dose
      examined (0.6 mg/h).

PMID- 25964030
TI  - Hyperbaric oxygen treatment for the critically ill patient.

PMID- 25964029
TI  - The uses of smartphones and tablet devices in surgery: A systematic review of the
      literature.
AB  - BACKGROUND: Smartphones and tablet devices have become ubiquitous, and their
      adoption in the health care arena is growing. Reviews have looked at their
      utilities within medical specialties. Despite the many surgical apps available
      currently, there has not been a comprehensive literature review evaluating uses
      of these platforms within surgical disciplines. We reviewed the literature
      systematically in this regard. METHODS: Embase, MEDLINE, Health Management
      Informatics Consortium, and PsychINFO databases were searched for empiric
      quantitative studies evaluating interventions based in the use of smartphone or
      tablet device within surgical disciplines targeted at surgeons, patients, or the
      wider public. RESULTS: Of the 39 studies included, 24 evaluated smartphone-based
      interventions and 15 looked at tablet devices, whereas 30 were app-based
      interventions and 9 were not. A wide range of effective and innovative utilities
      were identified and categorized into 8 domains; Diagnostics (n = 11),
      telemedicine (n = 9), operative navigation (n = 6), training (n = 5), data
      collection (n = 3), patient education (n = 2), behavior change (n = 2), and
      operative planning (n = 1). CONCLUSION: This comprehensive systematic literature
      review of smartphone and tablet device use in surgery demonstrates a wide range
      of innovative utilities in the pre-, intra-, and postoperative contexts. Although
      results of individual studies generally were favorable, limitations in
      methodologies existed in many, and although studies clearly highlight the
      substantial potential of smartphone and tablet devices in the surgical setting,
      trials of greater quality will be necessary to pave the way for their widespread
      adoption.

PMID- 25964031
TI  - Erratum--Hypdrophobicity: the link between bubbles, bubblers and autoimmunity?

PMID- 25964032
TI  - The effect of pre-dive ingestion of dark chocolate on endothelial function after
      a scuba dive.
AB  - OBJECTIVE: The aim of the study was to observe the effects of dark chocolate on
      endothelial function after scuba diving. METHODS: Forty-two male scuba divers
      were divided into two groups: a control (n=21) and a chocolate group (n=21). They
      performed a 33-metres deep scuba-air dive for 20 minutes in a diving pool (Nemo
      33, Brussels). Water temperature was 330C. The chocolate group ingested 30 g of
      dark chocolate (86% cocoa) 90 minutes before the dive. Flow-mediated dilatation
      (FMD), digital photoplethysmography and nitric oxide (NO) and peroxynitrites
      (ONOO-) levels were measured before and after the scuba dive in both groups.
      RESULTS: A significant decrease in FMD was observed in the control group after
      the dive (91+/-7% (mean+/-95% confidence interval) of pre-dive values; P<0.001)
      while it was increased in the chocolate group (105+/-5% of pre-dive values;
      P<0.001). No difference in digital photoplethysmography was observed between
      before and after the dives. No variation of circulating NO level was observed in
      the control group whereas an increase was shown in the chocolate group (154+/-73%
      of pre-dive values; P=0.04). A significant reduction in ONOO- was observed in the
      control group (84+/-12% of pre-dive values; P=0.003) whereas no variation was
      shown after the dive with chocolate intake (100+/-28% of pre-dive values; ns).
      CONCLUSIONS: Ingestion of 30 g of dark chocolate 90 minutes before scuba diving
      prevented post-dive endothelial dysfunction, as the antioxidants contained in
      dark chocolate probably scavenge free radicals.

PMID- 25964033
TI  - Flying after diving: should recommendations be reviewed? In-flight
      echocardiographic study in bubble-prone and bubble-resistant divers.
AB  - INTRODUCTION: Inert gas accumulated after multiple recreational dives can
      generate tissue supersaturation and bubble formation when ambient pressure
      decreases. We hypothesized that this could happen even if divers respected the
      currently recommended 24-hour pre-flight surface interval (PFSI). METHODS: We
      performed transthoracic echocardiography (TTE) on a group of 56 healthy scuba
      divers (39 male, 17 female) as follows: first echo--during the outgoing flight,
      no recent dives; second echo--before boarding the return flight, after a multiday
      diving week in the tropics and a 24-hour PFSI; third echo--during the return
      flight at 30, 60 and 90 minutes after take-off. TTE was also done after every
      dive during the week's diving. Divers were divided into three groups according to
      their 'bubble-proneness': non-bubblers, occasional bubblers and consistent
      bubblers. RESULTS: During the diving, 23 subjects never developed bubbles, 17
      only occasionally and 16 subjects produced bubbles every day and after every
      dive. Bubbles on the return flight were observed in eight of the 56 divers (all
      from the 'bubblers' group). Two subjects who had the highest bubble scores during
      the diving were advised not to make the last dive (increasing their PFSI to
      approximately 36 hours), and did not demonstrate bubbles on the return flight.
      CONCLUSIONS: Even though a 24-hour PFSI is recommended on the basis of clinical
      trials showing a low risk of decompression sickness (DCS), the presence of venous
      gas bubbles in-flight in eight of 56 divers leads us to suspect that in real-life
      situations DCS risk after such a PFSI is not zero.

PMID- 25964034
TI  - The five-minute prebreathe in evaluating carbon dioxide absorption in a closed
      circuit rebreather: a randomized single-blind study.
AB  - INTRODUCTION: Closed-circuit underwater rebreather apparatus (CCR) recycles
      expired gas through a carbon dioxide (CO2) 'scrubber'. Prior to diving, users
      perform a five-minute 'prebreathe' during which they self-check for symptoms of
      hypercapnia that might indicate a failure in the scrubber. There is doubt that
      this strategy is valid. METHODS: Thirty divers were block-randomized to breathe
      for five minutes on a circuit in two of the following three conditions: normal
      scrubber, partly-failed scrubber, and absent scrubber. Subjects were blind to
      trial allocation and instructed to terminate the prebreathe on suspicion of
      hypercapnia. RESULTS: Early termination was seen in 0/20, 2/20, and 15/20 of the
      normal, partly-failed, and absent absorber conditions, respectively. Subjects in
      the absent group experienced a steady, uncontrolled rise in inspired (PICO2) and
      end-tidal CO2 (PETCO2). Seven subjects exhibited little or no increase in minute
      volume yet reported dyspnoea at termination, suggesting a biochemically-mediated
      stimulus to terminate. This was consistent with results in the partly-failed
      condition (which resulted in a plateaued mean PICO2 near 20 mmHg), where a small
      increase in ventilation typically compensated for the inspired CO2 increase.
      Consequently, mean PETCO2 did not change and in the absence of a hypercapnic
      biochemical stimulus, subjects were very insensitive to this condition.
      CONCLUSIONS: While prebreathes are useful to evaluate other primary functions,
      the five-minute prebreathe is insensitive for CO2 scrubber faults in a
      rebreather. Partly-failed conditions are dangerous because most will not be
      detected at the surface, even though they may become very important at depth.

PMID- 25964035
TI  - An observation of venous gas emboli in divers and susceptibility to decompression
      sickness.
AB  - INTRODUCTION: Decompression sickness (DCS) results from the formation of bubbles
      within the tissues and blood in response to a reduction in environmental
      pressure. Venous gas emboli (VGE) are common after diving and are usually only
      present in small numbers. Greater VGE numbers are an indication of decompression
      stress, and can be reliably detected using ultrasound imaging. AIM: To examine
      the relationship between production of VGE following a routine dive and the risk
      of DCS. METHODS: A matched population of divers with and without a history of DCS
      were monitored for the production of VGE at 15-minute intervals using ultrasound,
      following a 405 kPa air dive in a hyperbaric chamber using the DCIEM air
      decompression table. VGE production was graded using a validated grading system
      and the data analysed to compare maximum VGE grade and duration of VGE formation.
      RESULTS: Eleven divers with a history of DCS were compared with 13 divers with no
      history of DCS. Divers with a history of DCS demonstrated both a higher maximum
      grade (P=0.04) and longer duration (P=0.002) of VGE production compared to divers
      without a history of DCS. CONCLUSION: Higher maximum VGE grades and longer
      durations of VGE following decompression were associated with a history of DCS
      and, in particular, musculoskeletal DCS. Although the exact mechanism of DCS
      remains poorly understood, our data suggest some individuals are inherently more
      prone to develop VGE, increasing the probability of DCS. Modification of diving
      practices in those with high VGE grades could potentially decrease DCS risk in
      these individuals.

PMID- 25964036
TI  - Hyperbaric oxygen therapy increases insulin sensitivity in overweight men with
      and without type 2 diabetes.
AB  - AIMS: The onset of insulin resistance is an important metabolic event in the
      development of type 2 diabetes. For patients with type 2 diabetes, we recently
      showed that peripheral insulin sensitivity was increased during hyperbaric oxygen
      treatment (HBOT). This study aims to investigate whether this occurs in a non
      patient population with and without type 2 diabetes, along with the mechanism of
      this effect. METHODS: Overweight and obese male participants were recruited from
      the community, 11 without and eight with type 2 diabetes. Insulin sensitivity was
      measured by the glucose infusion rate (GIR) during a hyperinsulinaemic
      euglycaemic clamp (80 mU.m-2.min-1) at baseline and during the third HBOT
      session. Monocyte chemo-attractant protein-1 (MCP-1), tumour necrosis factor
      alpha (TNF-alpha) and interleukin-6 (IL-6) were measured in fasting serum and
      adipose tissue samples taken for their gene expression at baseline and
      immediately following four HBOT sessions. Additional fasting serum samples were
      collected during the first HBOT at 0, 60 and 120 minutes, and 24-hours after the
      last HBOT. RESULTS: In response to HBOT, GIR was increased by 29+/-32% in those
      without (n=10, P=0.01), and by 57+/-66% in those with type 2 diabetes (n=7,
      P=0.04). This increase was maintained for 30 minutes post HBOT. Reduced MCP-1 and
      TNF-alpha were observed after HBOT, whereas IL-6 was increased only in
      individuals without diabetes and this correlated with the increase in insulin
      sensitivity (r2=0.72, P=0.004). CONCLUSIONS: Peripheral insulin sensitivity was
      increased following HBOT in overweight or obese males with and without type 2
      diabetes; this increase was maintained for at least 30 minutes post HBOT. Changes
      in inflammatory cytokines may partly explain this effect.

PMID- 25964037
TI  - Performance of the Baxter Infusor LV10 under hyperbaric conditions.
AB  - INTRODUCTION: Elastomeric drug delivery devices are a simple way to provide long
      term IV therapy to patients in the outpatient setting. Patients receiving
      hyperbaric oxygen therapy occasionally need these devices. This study compared
      the performance of the Baxter infusor LV10 elastomeric device in repetitive
      conditions at pressures of 101.3 kPa and 243 kPa. METHODS: Ten Baxter infusor
      LV10 elastomeric devices were pressurised in a hyperbaric chamber to 243 kPa over
      a two-hour period consistent with a standard medical treatment run. This process
      was repeated 10 times for each device giving a total of 20 hours under pressure.
      The fluid delivered by each device was measured and the device weighed at the end
      of each pressurisation. Ten control devices containing identical drugs were
      tested in the same manner at 101.3 kPa over the same time period. RESULTS: No
      significant differences in output of the devices were observed between hyperbaric
      and control conditions. The flow rates measured in both study groups were 35%
      lower than the manufacturer's stated flow rate, possibly due to lower test
      environment temperature and outdated devices used in the tests. CONCLUSION:
      Despite lower than expected flow rates, this study demonstrated no significant
      difference in the delivery rate of the Baxter infusor LV10 under 243 kPa
      hyperbaric conditions compared with room pressure.

PMID- 25964038
TI  - Hyperbaric oxygen therapy for intensive care patients: position statement by the
      European Committee for Hyperbaric Medicine.
AB  - Many of the accepted indications for hyperbaric oxygen treatment (HBOT) may occur
      in critically ill patients. HBOT itself may cause a number of physiological
      changes which may further compromise the patient's state. Guidelines on the
      management of critically ill patients in a hyperbaric facility have been founded
      on the conclusions of the 2007 European Committee for Hyperbaric Medicine (ECHM)
      meeting. With regard to patient management, HBOT should be included in the
      overall care of ICU patients only after a risk/benefit assessment related to the
      specifics of both the hyperbaric centre and the patient's clinical condition and
      should not delay or interrupt their overall management. Neither patient
      monitoring nor treatment should be altered or stopped due to HBOT, and any HBOT
      effects must be strictly evaluated and appropriately mitigated. With regard to
      the hyperbaric facility itself, the hyperbaric chamber should be specifically
      designed for ICU patients and should be fully equipped to allow continuation of
      patient monitoring and treatment. The hyperbaric chamber ideally should be
      located in, or around the immediate vicinity of the ICU, and be run by a
      sufficiently large and well-trained team of physicians, nurses, chamber operators
      and technicians. All devices to be introduced into the chamber should be
      evaluated, tested and acknowledged as safe for use in a hyperbaric environment
      and all procedures (standard and emergency) should be tested and written before
      being implemented. 

PMID- 25964039
TI  - Staffing and training issues in critical care hyperbaric medicine.
AB  - The integrated chain of treatment of the most severe clinical cases that require
      hyperbaric oxygen therapy (HBOT) assumes that intensive care is continued while
      inside the hyperbaric chamber. Such an approach needs to take into account all
      the risks associated with transportation of the critically ill patient from the
      ICU to the chamber and back, changing of ventilator circuits and intravascular
      lines, using different medical devices in a hyperbaric environment, advanced
      invasive physiological monitoring as well as medical procedures (infusions,
      drainage, etc) during long or frequently repeated HBOT sessions. Any medical
      staff who take care of critically ill patients during HBOT should be certified
      and trained according to both emergency/intensive care and hyperbaric
      requirements. For any HBOT session, the number of staff needed for any HBOT
      session depends on both the type of chamber and the patient's status--stable,
      demanding or critically ill. For a critically ill patient, the standard procedure
      is a one-to-one patient-staff ratio inside the chamber; however, the final
      decision whether this is enough is taken after careful risk assessment based on
      the patient's condition, clinical indication for HBOT, experience of the
      personnel involved in that treatment and the available equipment.

PMID- 25964040
TI  - Hyperbaric intensive care technology and equipment.
AB  - In an emergency, life support can be provided during recompression or hyperbaric
      oxygen therapy using very basic equipment, provided the equipment is hyperbaric
      compatible and the clinicians have appropriate experience. For hyperbaric
      critical care to be provided safely on a routine basis, however, a great deal of
      preparation and specific equipment is needed, and relatively few facilities have
      optimal capabilities at present. The type, size and location of the chamber are
      very influential factors. Although monoplace chamber critical care is possible,
      it involves special adaptations and inherent limitations that make it
      inappropriate for all but specifically experienced teams. A large, purpose
      designed chamber co-located with an intensive care unit is ideal. Keeping the
      critically ill patient on their normal bed significantly improves quality of care
      where this is possible. The latest hyperbaric ventilators have resolved many of
      the issues normally associated with hyperbaric ventilation, but at significant
      cost. Multi-parameter monitoring is relatively simple with advanced portable
      monitors, or preferably installed units that are of the same type as used
      elsewhere in the hospital. Whilst end-tidal CO2 readings are changed by pressure
      and require interpretation, most other parameters display normally. All normal
      infusions can be continued, with several examples of syringe drivers and infusion
      pumps shown to function essentially normally at pressure. Techniques exist for
      continuous suction drainage and most other aspects of standard critical care. At
      present, the most complex life support technologies such as haemofiltration,
      cardiac assist devices and extra-corporeal membrane oxygenation remain
      incompatible with the hyperbaric environment. 

PMID- 25964041
TI  - A pro/con review comparing the use of mono- and multiplace hyperbaric chambers
      for critical care.
AB  - Hyperbaric oxygen treatment (HBOT) of critically ill patients requires special
      technology and appropriately trained medical team staffing for '24/7' emergency
      services. Regardless of the chamber system used it is essential that the
      attending nurse and critical care specialist understand the physics and
      physiology of hyperbaric oxygen for safe treatment and compression/decompression
      procedures. Mechanical ventilation through endotracheal tube or tracheotomy is
      hampered by the increased gas density and flow resistance with risks of
      hypoventilation, carbon dioxide retention and oxygen seizures. Ventilation should
      be controlled and arterial and end-tidal carbon dioxide levels monitored.
      Haemodynamically unstable patients require careful risk-benefit evaluation,
      invasive monitoring and close supervision of inotropes, vasopressors and sedative
      drug infusions to avoid blood pressure swings and risk of awareness. Two
      distinctly different chambers are used for critical care. Small cost-efficient
      and easy-to-install acrylic monoplace chambers require less staffing and no
      inside attendant. Major disadvantages include patient isolation with difficulties
      to maintain standard organ support and invasive monitoring. Monoplace ventilators
      are less advanced and require the use of muscle relaxants and excessive sedation.
      Intravenous lines must be changed to specially designed IV pumps located outside
      the chamber with chamber pass-through and risk of inaccurate drug delivery. The
      multiplace chamber is better suited for HBOT of critically ill patients with
      failing vital functions and organ systems, primarily because it permits
      appropriate ICU equipment to be used inside the chamber by accompanying staff.
      Normal 'hands-on' intensive care continues during HBOT with close attention to
      all aspects of critical patient care. A regional trauma hospital-based
      rectangular chamber system immediately bordering critical care and emergency ward
      facilities is the best solution for safe HBOT in the critically ill.
      Disadvantages include long-term commitment, larger space requirements and higher
      capitalization, technical and staffing costs. 

PMID- 25964042
TI  - Diving injuries are (usually) no accident.

PMID- 25964043
TI  - Don't dive cold when you don't have to.

PMID- 25964044
TI  - Biofeedback Assisted Stress Management in Patients with Lung Cancer: A
      Feasibility Study.
AB  - Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death
      for men and women in the United States. NSCLC causes a variety of symptoms which
      result in significant distress and reduced quality of life for patients.
      Behavioral and other non-pharmacologic treatment interventions for NSCLC have
      resulted in improved quality of life, reduced emotional distress, and improved
      longevity. This study investigates the feasibility and effectiveness of
      biofeedback assisted stress management (BFSM) to reduce stress in patients with
      NSCLC. Because of patient dropout, this study was terminated prematurely. Despite
      this, evaluation of data revealed positive trends, with patients learning to
      reduce their stress, improve their respiration and heart rate variability, and
      improve coping. These trends suggest that patients with NSCLC can learn to self
      regulate physiology and BFSM may be useful for them, although a less ill patient
      population may be desirable for future investigations. 

PMID- 25964045
TI  - Anti-inflammatory activity of green versus black tea aqueous extract in a rat
      model of human rheumatoid arthritis.
AB  - AIM: Recently, there has been an increasing interest in tea (Camellia sinensis)
      as a protective agent against inflammatory diseases. Here, we evaluated/compared
      the anti-inflammatory activity of two different doses (0.5 and 1.0 g/kg body
      weight) of green tea aqueous extract (GTE, rich in catechins) and black tea
      aqueous extract (BTE, rich in theaflavins and thearubigins) in rat adjuvant
      induced arthritis (AIA). METHODS: Adjuvant-induced arthritis rat model received
      orally/daily distilled water as vehicle, indomethacin (1.0 mg/kg body weight; a
      non-steroidal/anti-inflammatory drug), or tea aqueous extracts (for 28 or 14
      consecutive days starting from day 0 or 14 of arthritis induction, respectively).
      RESULTS: The present study showed that only the high dose of GTE (from day 0)
      significantly alleviated (P < 0.05-0.001) all complications shown in arthritic
      rats, including synovial joint inflammation, elevation in erythrocyte
      sedimentation rate, blood leukocytosis (due to lymphocytosis and neutrocytosis),
      and changes in weight/cellularity of lymphoid organs. The anti-arthritic activity
      of the high dose of GTE (from day 0) was comparable (P > 0.05) with that of
      indomethacin (12.9-53.8 vs. 9.5-48.4%, respectively) and mediated by
      significantly decreasing and down-regulating (P < 0.001) the systemic production
      of pro-inflammatory cytokines and the expression of chemokine receptor-5 in
      synovial tissues, respectively. Moreover, the anti-arthritic activity of tea
      aqueous extracts was in the following order: high dose of GTE > low dose of GTE
      >= high dose of BTE > low dose of BTE. CONCLUSION: The present study proved the
      anti-inflammatory activity of GTE over BTE and equal to that of indomethacin in
      AIA rat model.

PMID- 25964046
TI  - Cell surface and in vivo interaction of dendrimeric N-glycoclusters.
AB  - While many examples have been reported that glycoclusters interact with target
      lectins more strongly than single molecules of glycans, through multivalency
      effects, literature examples to support lectin interactions/modulations on cell
      surface and in live animals is quite rare. Our N-glycoclusters, which were
      efficiently prepared by immobilizing 16 molecules of the asparagine-linked
      glycans (N-glycans) onto a lysine-based dendron template through histidine
      mediated Huisgen cycloaddition, were shown to efficiently detect platelet
      endothelial cell adhesion molecule (PECAM) on human umbilical vein endothelial
      cells (HUVEC) as a alpha(2-6)-sialylated oligosaccharides recognizing lectin.
      Furthermore, the identity of the N-glycans on our N-glycoclusters allowed control
      over organ-selective accumulation and serum clearance properties when
      intravenously injected into mice.

PMID- 25964047
TI  - A Study of Liposomal Formulations to Improve the Delivery of Aquated Cisplatin to
      a Multidrug Resistant Tumor.
AB  - PURPOSE: This study was aimed at exploring the use of liposomes to deliver
      aquated cisplatin (ACP), a metabolite of CDDP, with increased potency and
      toxicity. Three liposomal formulations were compared for delivery of ACP to a
      multidrug resistant tumor. METHODS: Three different liposomes (DMPC, DPPC and
      DSPC as the main lipid components) were loaded with ACP by the thin-film
      hydration method. In vitro drug release was assessed over 72 h at 37 degrees C in
      PBS. The pharmacokinetics of free CDDP and the three ACP liposomes was determined
      using ICP-AES and their efficacy against EMT6-AR1 multidrug resistant murine
      breast tumor was compared. RESULTS: The DSPC formulation, composed of a C18 acyl
      chain lipid, exhibited the slowest drug release (~2%) after 72 h at 37 degrees C,
      compared to the other two formulations with decreased carbon chain lengths (C16
      and C14; 7 and 25% release respectively). The pharmacokinetic profile was
      improved with all liposomal formulations relative to free CDDP, with clearance
      reduced by 500-fold for DSPC, 200-fold for DPPC and 130-fold for DMPC. The DSPC
      formulation displayed the highest drug accumulation in the tumor with 2-fold, 3
      fold and 100-fold increases compared to DPPC, DMPC and free CDDP respectively.
      The DSPC formulation significantly inhibited the EMT6-AR1 tumor growth by ~90%,
      while the other formulations displayed no statistically significant improved
      activity compared to saline. CONCLUSION: These results suggest that the DSPC
      liposomal formulation is a promising formulation for MDR tumor therapy over DMPC
      and DPPC formulations and free drug.

PMID- 25964048
TI  - Stealth Nanogels of Histinylated Poly Ethyleneimine for Sustained Delivery of
      Methotrexate in Collagen-Induced Arthritis Model.
AB  - PURPOSE: The study aimed to illustrate application of polycation Stealth nanogels
      for sustained delivery of methotrexate (MTX) in collagen induced arthritis (CIA)
      model in C57Bl/6 mice. METHODS: Nanogel synthesis involves metal ion coordinated
      self-assembly of PEGylated poly ethyleneimine (L-histidine substituted), chemical
      crosslinking and subsequent removal of the coordinated metal. The nanogels were
      characterized by TEM and DLS-zeta potential. Comparative efficacy and
      pharmacokinetics of the i.v. administred MTX-loaded nanogels were investigated in
      the CIA model. Inflammation site passive accumulation of the fluorophore-labeled
      nanogels was tested using in-vivo imaging of mice paw received unilateral
      injection of lipopolysaccharide. RESULTS: Uniform nanogels (sizes ~40 nm by TEM)
      were loaded with MTX (entrapment efficiency = 62% and drug loading = 54% at the
      MTX feeding ratio of 0.3 relative to total molar concentration of the polymer
      amines). The nanogels exhibited neutral surface charge and an acceptable
      biocompatibility in terms of albumin aggregation, hemolysis, erythrocyte
      aggregation and cytotoxicity. Single dose pharmacokinetics of the MTX-loaded
      nanogels, unlike free drug, showed a sustained plasma profile. When arthritis
      established as confirmed by histopathology, a remarkable decline of paw swelling
      and clinical scores was observed. Fluorescence intensity of the nanogels was
      enhanced about 2.7 folds at the inflamed than control normal ankle. CONCLUSION:
      Sustained delivery of MTX and preferential accumulation of the nanogels in
      inflamed paw might explain the superior clinical outcome of the MTX-loaded
      nanogels.

PMID- 25964049
TI  - Spatial modulation spectroscopy for imaging and quantitative analysis of single
      dye-doped organic nanoparticles inside cells.
AB  - Imaging of non-fluorescent nanoparticles in complex biological environments, such
      as the cell cytosol, is a challenging problem. For metal nanoparticles, Rayleigh
      scattering methods can be used, but for organic nanoparticles, such as dye-doped
      polymer beads or lipid nanoparticles, light scattering does not provide good
      contrast. In this paper, spatial modulation spectroscopy (SMS) is used to image
      single organic nanoparticles doped with non-fluorescent, near-IR croconaine dye.
      SMS is a quantitative imaging technique that yields the absolute extinction cross
      section of the nanoparticles, which can be used to determine the number of dye
      molecules per particle. SMS images were recorded for particles within EMT-6
      breast cancer cells. The measurements allowed mapping of the nanoparticle
      location and the amount of dye in a single cell. The results demonstrate how SMS
      can facilitate efforts to optimize dye-doped nanoparticles for effective
      photothermal therapy of cancer. 

PMID- 25964050
TI  - Survival and complications of skeletal reconstructions after surgical treatment
      of bony metastatic renal cell carcinoma.
AB  - Improvements in survival for patients with renal cell carcinoma have resulted in
      an increase in the burden of disease due to skeletal metastases, which are often
      solitary and resistant to radiotherapy. Surgical intervention remains a valid
      treatment to improve function and relieve pain, and replacement is able to
      achieve this and improve disease free implant survival. The aim of this study was
      identify prognostic factors for reconstruction survival of skeletal metastases in
      renal cell carcinoma and to characterise the nature of the reconstruction related
      complications. A retrospective analysis of all patients treated for metastatic
      renal cell carcinoma in three international bone tumour units between 2000 and
      2014 identified 268 surgical interventions suitable for inclusion. Reconstruction
      survivorship was calculated using the Kaplan-Meier method whilst factors
      affecting reconstruction survival were assessed using Cox-regression multivariate
      analysis. Differences in proportions were assessed using Fisher's exact test. The
      overall rate of complications was 17%, which were classified as structural
      failure (7.1%), infection (4.9%) and tumour progression (3.7%). Endoprosthetic
      replacement when performed as the primary procedure demonstrate the best
      survivorship whilst factors associated with compromised reconstruction survival
      included previous surgical intervention and pre operative radiotherapy, and
      intralesional resection margins. We conclude that endoprosthetic replacement be
      considered as the index surgical intervention for skeletal metastases from renal
      cell carcinoma in certain locations as this carries the lowest incidence of
      complications. Revision of previous skeletal stabilisation, especially when
      combined with radiotherapy carries a high risk of complication, including
      infection, which often necessitates amputation. 

PMID- 25964051
TI  - Warthin's tumor of the larynx: a very rare case and systematic review of the
      literature.
AB  - BACKGROUND: Warthin's tumor or cystadenolymphoma (CAL) is a benign salivary gland
      tumor occurring almost exclusively in the parotid gland. CALs of other locations
      are rare. CASE PRESENTATION: We report a laryngeal CAL detected in a positron
      emission tomography/computed tomography (PET/CT) performed for breast cancer
      follow-up. The tumor was successfully treated by transoral surgery. DISCUSSION:
      Only 14 cases of laryngeal CAL are reported worldwide. These cases confirmed our
      experience of an uncomplicated and mostly successful transoral resection.
      CONCLUSION: CALs of the larynx are very rare. They are characterized by
      hypermetabolism in PET/CT. The increasing use of PET/CT investigations in cancer
      patients could give rise to more incidental findings of CALs at unusual locations
      such as the larynx.

PMID- 25964052
TI  - p110Delta Inhibits Monocyte Infiltration by Thioglycollate-Induced Periotoneal
      Inflammation but Not HCD-Induced Inflammation and Atherosclerosis in APOE KO
      Mice.
AB  - We have previously reported that phosphoinositide 3-kinase p110delta knockout
      (p110delta KO) diminished the adhesion of leukocytes to capillary venules and
      suppressed the peritoneal infiltration of leukocytes, both functions that play
      important roles in atherosclerosis. Therefore, we hypothesized that p110delta
      deficiency might be protective against atherosclerosis. Apolipoprotein E knockout
      (ApoE KO) mice were crossed with p110delta KO mice to generate homozygous double
      knockout mice (ApoE/p110delta DKO). The present study showed that ApoE/p110delta
      DKO mice fed with a high cholesterol diet (HCD) demonstrated less peritoneal
      infiltration of leukocytes and monocytes compared with ApoE KO mice after
      intraperitoneal injection of thioglycollate, an inducer of acute peritoneal
      inflammation. Unexpectedly, atherosclerosis in the aortic root and in the entire
      aorta was similar between the ApoE/p110delta DKO and ApoE KO groups. No
      difference in Mac-3 expression, indicative of macrophage infiltration, was found
      between the two groups. Further analysis showed that ApoE KO mice chronically fed
      with HCD had increased levels of total cholesterol, low-density lipoprotein in
      the blood and counts and percentages of circulating monocytes compared with ApoE
      KO mice fed with a normal diet. Consistently, the deficiency of p110delta
      affected neither the counts nor the percentages of monocytes nor the lipid
      profiles in the blood. The results suggested that p110delta plays an important
      role in acute but not in chronic inflammation, the latter being included in the
      early characteristics of atherosclerosis, which might explain the finding that
      p110delta deficiency fails to inhibit early atherosclerosis. 

PMID- 25964053
TI  - Chronic hyperglycemia is associated with acute kidney injury in patients
      undergoing CABG surgery--a cohort study.
AB  - BACKGROUND: Chronic hyperglycemia (CHG) with HbA1c as an indicator affects
      postoperative mortality and morbidity after coronary artery bypass grafting
      surgery (CABG). Acute kidney injury (AKI) is one of the frequent postoperative
      complications after CABG impacting short-and long-term outcomes. We investigated
      the association between CHG and postoperative incidence of AKI in CABG patients
      with and without history of diabetes mellitus (DM). METHODS: This cohort study
      consecutively enrolled patients undergoing CABG in 2009 at the department for
      cardiovascular surgery. CHG was defined as HbA1c >= 6.0%. Patients with advanced
      chronic kidney disease (CKD) were excluded. The incidence of postoperative AKI
      and its association with CHG was analyzed by univariate and multivariate logistic
      regression modeling. RESULTS: Three-hundred-seven patients were analyzed. The
      incidence of AKI was 48.2%. Patients with CHG (n = 165) were more likely to be
      female and had greater waist circumference as well as other comorbid conditions,
      such as smoking, history of DM, CKD, hypertension, pulmonary hypertension, and
      chronic obstructive pulmonary disease (all p <= 0.05). Preoperative eGFR, atrial
      fibrillation (AF), history of DM and CHG were associated with an increased risk
      of postoperative AKI in univariate analyses. In multivariate modelling, history
      of DM as well as preoperative eGFR and AF lost significance, while age, CHG and
      prolonged OP duration (p < 0.05) were independently associated with postoperative
      AKI. CONCLUSIONS: Our results suggest that CHG defined on a single measurement of
      HbA1c >= 6.0% was associated with the incidence of AKI after CABG. This finding
      might implicate that treatment decisions, including the selection of operative
      strategies, could be based on HbA1c measurement rather than on a recorded history
      of diabetes.

PMID- 25964054
TI  - BubR1 kinase: protection against aneuploidy and premature aging.
AB  - The multidomain protein kinase BubR1 is a central component of the mitotic
      spindle assembly checkpoint (SAC), an essential self-monitoring system of the
      eukaryotic cell cycle that ensures the high fidelity of chromosome segregation by
      delaying the onset of anaphase until all chromosomes are properly bi-oriented on
      the mitotic spindle. We discuss the roles of BubR1 in the SAC and the
      implications of BubR1-mediated interactions that protect against aneuploidy. We
      also describe the emerging roles of BubR1 in cellular processes that extend
      beyond the SAC, discuss how mice models have revealed unanticipated functions for
      BubR1 in the regulation of normal aging, and the potential role of BubR1 as
      therapeutic target for the development of innovative anticancer therapies. 

PMID- 25964055
TI  - Integrin-Linked Kinase, Snail and Multidrug Resistance Protein 1: Three
      concordant players in the progression of non-small cell lung cancer.
AB  - BACKGROUND: Integrin Linked Kinase (ILK), Snail and Multidrug Resistance Protein
      1 (MRP1) have been implicated in several cancers; however, their roles in non
      small cell lung cancer (NSCLC) remain to be elucidated. AIM: Investigation of
      their expression in NSCLC tissue. Relationships among these proteins and their
      association with clinicopathological parameters were studied. MATERIALS AND
      METHODS: ILK, Snail and MRP1 expression were immunohistochemically assessed in 97
      tumor tissues. Furthermore, western blot analysis for ILK, Snail and MRP1 in 6
      cases of NSCLC was also performed. RESULTS: ILK overexpression, positive Snail
      and MRP1 expression were found in 46.4%, 36.1% and 49.5% of tumors respectively.
      ILK expression was significantly correlated with tumor grade (p=0.013), lymph
      node (LN) metastases (p=0.001) and stage (p=0.001). Positive Snail and MRP1
      expression were significantly associated with LN metastasis (p=0.004 and 0.022,
      respectively) and advanced stage disease (p=0.018 and 0.024, respectively). MRP1
      expression was significantly higher among adenocarcinoma cases compared to other
      types (p=0.001). ILK over-expression was significantly associated with up
      regulation of Snail and MRP1 (p<0.001 both). Significant association was also,
      found between Snail and MRP1 expression (p=0.005). Moreover, the co-expression of
      two markers or more was significantly associated with less differentiation
      (p=0.011), advanced tumor status (p=0.030), LN metastasis (p<0.001) and advanced
      stage (p<0.001) disease. Western blot analysis validated immunohistochemical
      findings. CONCLUSION: ILK may have an important role in the progression of NSCLC,
      possibly through up-regulation of Snail and MRP1. ILK, Snail and MRP1 are
      important molecular markers for predicting carcinogenesis and progression of
      NSCLC.

PMID- 25964056
TI  - Quality of life correlation with socioeconomic status in Korean hepatitis-B
      patients: a cross sectional study.
AB  - BACKGROUND: In Korea, more than two-thirds of hepatocellular carcinoma patients
      are hepatitis B virus (HBV) surface antigen-seropositive. The effects of HBV
      infection on health-related quality of life (HRQoL) are important aspects in the
      overall management of HBV infection. However, other effects of other parameters
      on HBV patient HRQoL remain unknown and require clarification. Our study
      evaluated HRQoL in hepatitis-B patients, according to socioeconomic status.
      METHODS: We used community health survey data to analyze the relationship between
      HRQoL of HBV(+) patients according to socioeconomic status. We used propensity
      score matching (Ratio = 1:5) to balancing the patients and general population.
      Final analytic sample consisted of 7,098 hepatitis B patients and compared group
      (35,490 general populations). We examined the HRQoL in HBV(+) patients (n =
      7,098), stratified by socioeconomic status, compared with general populations,
      using the EuroQOL visual analog scale (EQ-VAS) and EQ-5D questionnaires. We used
      the Chi-square test and ANOVA to compare demographic variables. Multiple linear
      regression analysis identified associations between demographic variables and
      HRQoL. RESULTS: Participants with hepatitis B numbered 7,098 (16.7 %) of the
      study population. HRQoL was lower in hepatitis-B patients compared to the general
      population (EQ-VAS: -0.985, p = 0.0004; EQ-5D: -0.673, p = 0.0003). According to
      occupation type, clerks (EQ-VAS: -2.628, p = 0.0030; EQ-5D: -0.802, p = 0.0099)
      and managers and professionals (EQ-VAS: -1.518, p = 0.0356) had the lowest
      HRQoLs. Higher family income and education level groups had lower HRQoLs compared
      to the general population. CONCLUSIONS: Patients from higher socioeconomic status
      groups had HRQoLs that were more affected by hepatitis B. Thus, we require more
      accurate information about the disease to develop appropriate patient management
      guidelines. This will facilitate formulating policies and management strategies
      that alleviate HRQoL declines in HBV(+) patients.

PMID- 25964058
TI  - Evaluation and clinical quantification of neoplastic lesions and physiological
      structures in TOF-PET/MRI and non-TOF/MRI - a pilot study.
AB  - PURPOSE: To clinically assess a new PET/MRI technology in which the PET-
      component features a new PET-- detector and time--of--flight (TOF) technology.
      Thus, we compared SUVmax/mean of neoplastic lesions and physiological structures
      between TOF-- and non--TOF--PET/MRI imaging. We qualitatively evaluated image
      quality derived from TOF-PET/MRI, non--TOF--PET/MRI reconstruction and FDG-
      PET/CT. Lastly we did clinical measurements to evaluate the PET-- detector
      sensitivity in order to better understand the background of our clinical results.
      MATERIALS AND METHODS: Twenty--seven oncological patients were prospectively
      enrolled and evaluated with FDG-PET/CT and PET/MRI (15 M/ 12 F; mean age 56 +/-10
      y). Time between injection and PET/CT was 62.4 +/-7.6 min, consecutive start of
      imaging of PET/MRI was 104.6 min+/-18.2 after injection. To assess the
      differences between TOF and non--TOF, all PET--images of the PET/MRI were
      reconstructed twice -with and without TOF. To compare lesion and tissue
      characterization between both reconstructions, malignant lesions as well as
      physiological structures were compared. Furthermore, PET image quality,
      artifacts, image sharpness, noise and lesion detectability were assessed as well.
      Count rates between both systems were also compared. RESULTS: All malignant
      lesions and the majority of physiologic tissue (except the subcutaneous fat,
      spleen and blood pool) showed a good correlation concerning SUV (max and mean)
      measurements between PET/CT, non--TOF and TOF reconstructions. The general image
      quality was rated statistically significant superior in non--TOF (p<0.001) and
      TOF-reconstruction in PET/MRI (p<0.01) compared to PET/CT. Furthermore, TOF-
      PET/MRI was rated superior concerning image quality (p<0.05) compared to non--TOF
      PET/MRI. The ratio of emitted/received events between both systems (PET/CT and
      PET/MRI) was 2.78. CONCLUSION: PET/MRI with TOF is reliable concerning SUV
      quantification and image quality. The technical promise of an improved
      sensitivity of the new PET--detector in this PET/MRI device could be confirmed in
      a clinical setting.

PMID- 25964057
TI  - Neuropathologic assessment of participants in two multi-center longitudinal
      observational studies: the Alzheimer Disease Neuroimaging Initiative (ADNI) and
      the Dominantly Inherited Alzheimer Network (DIAN).
AB  - It has been hypothesized that the relatively rare autosomal dominant Alzheimer
      disease (ADAD) may be a useful model of the more frequent, sporadic, late-onset
      AD (LOAD). Individuals with ADAD have a predictable age at onset and the
      biomarker profile of ADAD participants in the preclinical stage may be used to
      predict disease progression and clinical onset. However, the extent to which the
      pathogenesis and neuropathology of ADAD overlaps with that of LOAD is equivocal.
      To address this uncertainty, two multicenter longitudinal observational studies,
      the Alzheimer Disease Neuroimaging Initiative (ADNI) and the Dominantly Inherited
      Alzheimer Network (DIAN), leveraged the expertise and resources of the existing
      Knight Alzheimer Disease Research Center (ADRC) at Washington University School
      of Medicine, St. Louis, Missouri, USA, to establish a Neuropathology Core (NPC).
      The ADNI/DIAN-NPC is systematically examining the brains of all participants who
      come to autopsy at the 59 ADNI sites in the USA and Canada and the 14 DIAN sites
      in the USA (eight), Australia (three), UK (one) and Germany (two). By 2014, 41
      ADNI and 24 DIAN autopsies (involving nine participants and 15 family members)
      had been performed. The autopsy rate in the ADNI cohort in the most recent year
      was 93% (total since NPC inception: 70%). In summary, the ADNI/DIAN NPC has
      implemented a standard protocol for all sites to solicit permission for brain
      autopsy and to send brain tissue to the NPC for a standardized, uniform and state
      of-the-art neuropathologic assessment. The benefit to ADNI and DIAN of the
      implementation of the NPC is very clear. The NPC provides final "gold standard"
      neuropathological diagnoses and data against which the antecedent observations
      and measurements of ADNI and DIAN can be compared. 

PMID- 25964059
TI  - Screening of differential microRNA expression in gastric signet ring cell
      carcinoma and gastric adenocarcinoma and target gene prediction.
AB  - Gastric signet ring cell carcinoma (GSRCC) is a unique pathological type of
      gastric carcinoma that is extremely invasive and has a poor prognosis after
      diagnosis. The expression of microRNAs has been closely linked to the
      carcinogenesis of gastric cancer and has been considered as a powerful prognostic
      marker. Distinctive expression of miRNAs in GSRCC was investigated in the present
      study. Samples of GSRCC were compared to that of intestinal gastric
      adenocarcinoma using Agilent microarray technique, and two differentially
      expressed miRNAs were identified, hsa-miR-665 and hsa-miR-95. qRT-PCR
      verification showed downregulation of both miRNAs in signet ring cell carcinoma
      and upregulation in gastric adenocarcinoma, which was not consistent with the
      results obtained by the microarray. Target gene prediction using online databases
      conferred two strong candidate genes, GLI2 and PLCG1. GO/KO analysis of these two
      genes showed close correlations with carcinogenesis and chemoresistance. It was
      concluded that hsa-miR-665 and hsa-miR-95 were downregulated in GSRCC but
      upregulated in intestinal gastric adenocarcinoma, and the relatively differential
      expression of the miRNAs negatively controlling their target genes could be
      closely related to the high invasive metastasis and chemoresistance of GSRCC. 

PMID- 25964060
TI  - Treadmill running improves hindlimb arteriolar endothelial function in type 1
      diabetic mice as visualized by X-ray microangiography.
AB  - BACKGROUND: Vascular function is impaired in patients with diabetes, however
      diabetic vascular dysfunction is ameliorated by exercise training. We aimed to
      clarify which hindlimb arterial segments are affected by treadmill running in the
      hindlimbs of streptozocin-induced type 1 diabetic mice in vivo. METHODS: Mice
      were divided into 3 groups; healthy control, diabetic control, and diabetic
      running groups. The exercise regimen was performed by treadmill level running
      mice for 60 min/day, for 4 weeks. Thereafter, we examined the vascular response
      to systemic acetylcholine administration in the left hindlimb of anesthetized
      ventilated mice using either 1) X-ray microangiography to visualize the arteries
      or 2) ultrasonic flowmetry to record the femoral arterial blood flow. RESULTS: X
      ray imaging clearly visualized the hindlimb arterial network (~70-250 MUm
      diameter). The vasodilator response to acetylcholine was significantly attenuated
      locally in the arterioles <100 MUm diameter in the diabetic group of mice
      compared to the control group of mice. Post-acetylcholine administration, all
      groups showed an increase in hindlimb vascular conductance, but the diabetic mice
      showed the smallest increase. Overall, compared to the diabetic mice, the
      treadmill-running mice exhibited a significant enhancement of the vasodilator
      response within the arterioles with diabetes-induced vasodilator dysfunction.
      CONCLUSIONS: Diabetes impaired acetylcholine-induced vasodilator function locally
      in the arteries <100 MUm diameter and decreased hindlimb vascular conductance
      responded to acetylcholine, while regular treadmill running significantly
      ameliorated the impaired vasodilator function, and enhanced the decreased
      conductance in the diabetic mice.

PMID- 25964061
TI  - Determination of optimal storage temperature and duration for analysis of total
      and isoenzyme lactate dehydrogenase activities in canine serum and cerebrospinal
      fluid.
AB  - BACKGROUND: Lactate dehydrogenase (LDH) exists as 5 isoenzymes in both serum and
      cerebrospinal fluid (CSF). Human studies have demonstrated that changes in LDH
      activity can be correlated with a particular disease. OBJECTIVES: Conflicting
      reports regarding the stability of LDH made it necessary to determine storage
      conditions before further study of the diagnostic power of this enzyme's activity
      can be pursued in dogs. The purpose of this study was to optimize measurement of
      LDH activity and analysis of its isoenzyme profile in canine serum and CSF
      through proper storage. METHODS: Serum and CSF were collected from 5 healthy
      dogs. Samples were stored at 22 degrees C, 4 degrees C, or -20 degrees C for up
      to 2 months. Total LDH activity was measured spectrophotometrically. Isoenzyme
      profiles were determined using the QuickGel LDH Isoenzyme technique and
      densitometric scanning. Retention of > 70% LDH activity in stored samples was
      considered clinically acceptable. RESULTS: Serum and CSF stored at -20 degrees C
      retained > 85% of the total LDH activity for 4 weeks, although CSF total LDH
      activity degraded by > 10% within 24 hours of storage. All serum LDH isoenzymes
      retained > 85% activity for up to 4 weeks at -20 degrees C. CSF LDH isoenzyme
      activity degraded rapidly, therefore CSF LDH should be evaluated within 72 hours
      to assure > 75% of LDH isoenzyme activity. CONCLUSIONS: Proper storage at -20
      degrees C can optimize detection of total LDH activity and the LDH isoenzyme
      profile in canine serum and CSF. This information is important for evaluating the
      potential usefulness of LDH in veterinary medicine.

PMID- 25964062
TI  - Dispersal of a defensive symbiont depends on contact between hosts, host health,
      and host size.
AB  - Symbiont dispersal is necessary for the maintenance of defense mutualisms in
      space and time, and the distribution of symbionts among hosts should be
      intricately tied to symbiont dispersal behaviors. However, we know surprisingly
      little about how most defensive symbionts find and choose advantageous hosts or
      what cues trigger symbionts to disperse from their current hosts. In a series of
      six experiments, we explored the dispersal ecology of an oligochaete worm
      (Chaetogaster limnaei) that protects snail hosts from infection by larval
      trematode parasites. Specifically, we determined the factors that affected net
      symbiont dispersal from a current "donor" host to a new "receiver" host.
      Symbionts rarely dispersed unless hosts directly came in contact with one
      another. However, symbionts overcame their reluctance to disperse across the open
      environment if the donor host died. When hosts came in direct contact, net
      symbiont dispersal varied with both host size and trematode infection status,
      whereas symbiont density did not influence the probability of symbiont dispersal.
      Together, these experiments show that symbiont dispersal is not a constant,
      random process, as is often assumed in symbiont dispersal models, but rather the
      probability of dispersal varies with ecological conditions and among individual
      hosts. The observed heterogeneity in dispersal rates among hosts may help to
      explain symbiont aggregation among snail hosts in nature. 

PMID- 25964063
TI  - Soil biota effects on local abundances of three grass species along a land-use
      gradient.
AB  - Biotic plant-soil interactions and land-use intensity are known to affect plant
      individual fitness as well as competitiveness and therefore plant-species
      abundances in communities. Therefore, a link between soil biota and land-use
      intensity on local abundance of plant species in grasslands can be expected. In
      two greenhouse experiments, we investigated the effects of soil biota from
      grassland sites differing in land-use intensity on three grass species that vary
      in local abundances along this land-use gradient. We were interested in those
      soil-biota effects that are associated with land-use intensity, and whether these
      effects act directly or indirectly. Therefore, we grew the three plant species in
      two separate experiments as single individuals and in mixtures and compared their
      performance. As single plants, all three grasses showed a similar performance
      with and without soil biota. In contrast, in mixtures growth of the species in
      response to the presence or absence of soil biota differed. This resulted in
      different soil-biota effects that tend to correspond with patterns of species
      specific abundances in the field for two of the three species tested. Our results
      highlight the importance of indirect interactions between plants and soil
      microorganisms and suggest that combined effects of soil biota and plant-plant
      interactions are involved in structuring plant communities. In conclusion, our
      experiments suggest that soil biota may have the potential to alter effects of
      plant-plant interactions and therefore influence plant-species abundances and
      diversity in grasslands. 

PMID- 25964064
TI  - Evaluation of the Temporal Acoustic Window for Transcranial Doppler in a Multi
      Ethnic Population in Brazil.
AB  - The aim of this study was to relate the presence of a temporal acoustic window
      (TAW) to the variables sex, age and race. This observational study was conducted
      in patients under etiologic investigation after stroke, sickle-cell anemia and
      hospitalization in an intensive therapy neurologic unit. TAW presence was
      confirmed by bilateral assessment by two neurologists via transcranial Doppler
      (TCD). Multiple logistic regression was performed to explain the presence of the
      window as a function of sex, age and race. In 20% of the 262 patients evaluated,
      a TAW was not present. The incidence of TAW presence was greater in men (odds
      ratio [OR] = 5.4, 95% confidence interval [CI] = 2.5-11.7, p < 0.01); lower with
      increased age (OR = 0.9, 95% CI = 0.92-0.97, p < 0.01); and lower among those of
      African and Asian descent (OR = 0.32, 95% CI = 0.14-0.70, p = 0.005). On the
      basis of the results, more men than women had TAWs, and the decrease in TAWs was
      associated with increased age and African or Asian descent. 

PMID- 25964065
TI  - Panorama Ultrasound for Navigation and Guidance of Epidural Anesthesia.
AB  - Despite the common use of epidural anesthesia in obstetrics and surgery, the
      procedure can be challenging, especially for obese patients. We propose the use
      of an ultrasound guidance system employing a transducer-mounted camera to create
      3-D panorama ultrasound volumes of the spine, thereby allowing identification of
      vertebrae and selection of puncture site, needle trajectory and depth of
      insertion. The camera achieves absolute position estimation of the transducer
      with respect to the patient using a specialized marker strip attached to the skin
      surface. The guidance system is validated first on a phantom against a commercial
      optical tracking system and then in vivo by comparing panorama images from human
      subjects against independent measurements by an experienced sonographer. The
      results for measuring depth to the epidural space, intervertebral spacing and
      registration of interspinous gaps to the skin prove the potential of the system
      for improving guidance of epidural anesthesia. The tracking and visualization are
      implemented in real time using the 3D Slicer software package. 

PMID- 25964066
TI  - Chick embryos have the same pattern of hypoxic lower-brain activation as fetal
      mammals.
AB  - cFos expression (indicating a particular kind of neuronal activation) was
      examined in embryonic day (E) 18 chick embryos after exposure to 4 h of either
      normoxia (21% O2), modest hypoxia (15% O2), or medium hypoxia (10% O2). Eight
      regions of the brainstem and hypothalamus were surveyed, including seven
      previously shown to respond to hypoxia in late-gestation mammalian fetuses (Breen
      et al., 1997; Nitsos and Walker, 1999b). Hypoxia-related changes in chick embryo
      brain activation mirrored those found in fetal mammals with the exception of the
      medullary Raphe, which showed decreased hypoxic activation, compared with no
      change in mammals. This difference may be explained by the greater anapyrexic
      responses of chick embryos relative to mammalian fetuses. Activation in the A1/C1
      region was examined in more detail to ascertain whether an O2-sensitive
      subpopulation of these cells containing heme oxygenase 2 (HMOX2) may drive
      hypoxic brain responses before the maturation of peripheral O2-sensing. HMOX2
      positive and -negative catecholaminergic cells and interdigitating
      noncatecholaminergic HMOX2-positive cells all showed significant changes in cFos
      expression to hypoxia, with larger population responses seen in the
      catecholaminergic cells. Hypoxia-induced activation of lower-brain regions
      studied here was significantly better correlated with activation of the nucleus
      of the solitary tract (NTS) than with that of HMOX2-containing A1/C1 neurons.
      Together, these observations suggest that (1) the functional circuitry
      controlling prenatal brain responses to hypoxia is strongly conserved between
      birds and mammals, and (2) NTS neurons are a more dominant driving force for
      prenatal hypoxic cFos brain responses than O2-sensing A1/C1 neurons.

PMID- 25964067
TI  - Iron incorporation into MnSOD A (bacterial Mn-dependent superoxide dismutase)
      leads to the formation of a peroxidase/catalase implicated in oxidative damage to
      bacteria.
AB  - BACKGROUND: Mn/Fe-superoxide dismutase (SOD) is a family of enzymes essential for
      organisms to be able to cope with oxygen. These enzymes bound to their classical
      metals catalyze the dismutation of the free radical superoxide anion (O2(-)) to
      H2O2 and molecular oxygen. E. coli has the manganese-dependent SOD A and the iron
      dependent SOD B. METHODS: Strains of E. coli overexpressing SOD A or SOD B were
      grown in media with different metal compositions. SODs were purified and their
      metal content and SOD activity were determined. Those proteins were incubated
      with H2O2 and assayed for oxidation of Amplex red or o-phenylenediamine,
      consumption of H2O2, release of iron and protein radical formation. Cell survival
      was determined in bacteria with MnSOD A or FeSOD A after being challenged with
      H2O2. RESULTS: We show for the first time that the bacterial manganese-dependent
      SOD A when bound to iron (FeSOD A) has peroxidase activity. The in vivo formation
      of the peroxidase FeSOD A was increased when media had higher levels of iron
      because of a decreased manganese metal incorporation. In comparison to bacteria
      with MnSOD A, cells with FeSOD A had a higher loss of viability when exposed to
      H2O2. GENERAL SIGNIFICANCE: The biological occurrence of this fundamental
      antioxidant enzyme in an alternative iron-dependent state represents an important
      source of free radical formation.

PMID- 25964069
TI  - Intracellular pH imaging in cancer cells in vitro and tumors in vivo using the
      new genetically encoded sensor SypHer2.
AB  - BACKGROUND: Measuring intracellular pH (pHi) in tumors is essential for the
      monitoring of cancer progression and the response of cancer cells to various
      treatments. The purpose of the study was to develop a method for pHi mapping in
      living cancer cells in vitro and in tumors in vivo, using the novel genetically
      encoded indicator, SypHer2. METHODS: A HeLa Kyoto cell line stably expressing
      SypHer2 in the cytoplasm was used, to perform ratiometric (dual excitation)
      imaging of the probe in cell culture, in 3D tumor spheroids and in tumor
      xenografts in living mice. RESULTS: Using SypHer2, pHi was demonstrated to be
      7.34+/-0.11 in monolayer HeLa cells in vitro under standard cultivation
      conditions. An increasing pHi gradient from the center to the periphery of the
      spheroids was displayed. We obtained fluorescence ratio maps for HeLa tumors in
      vivo and ex vivo. Comparison of the map with the pathomorphology and with hypoxia
      staining of the tumors revealed a correspondence of the zones with higher pHi to
      the necrotic and hypoxic areas. CONCLUSIONS: Our results demonstrate that pHi
      imaging with the genetically encoded pHi indicator, SypHer2, can be a valuable
      tool for evaluating tumor progression in xenograft models. GENERAL SIGNIFICANCE:
      We have demonstrated, for the first time, the possibility of using the
      genetically encoded sensor SypHer2 for ratiometric pH imaging in cancer cells in
      vitro and in tumors in vivo. SypHer2 shows great promise as an instrument for pHi
      monitoring able to provide high accuracy and spatiotemporal resolution.

PMID- 25964068
TI  - An efficient and cost-effective approach to kahalalide F N-terminal modifications
      using a nuisance algal bloom of Bryopsis pennata.
AB  - BACKGROUND: Kahalalide F (KF) and its isomer iso-kahalalide F (isoKF), both of
      which can be isolated from the mollusk Elysia rufescens and its diet alga
      Bryopsis pennata, are potent cytotoxic agents that have advanced through five
      clinical trials. Due to a short half-life, narrow spectrum of activity, and a
      modest response in patients, further efforts to modify the molecule are required
      to address its limitations. In addition, due to the high cost in producing KF
      analogues using solid phase peptide synthesis (SPPS), a degradation and
      reconstruction approach was employed using natural KF from a seasonal algal bloom
      to generate KF analogues. METHODS: N-protected KF was carefully hydrolyzed at the
      amide linkage between l-Thr12 and d-Val13 using dilute HCl. The synthesis of the
      C-terminal fragment began with the formation of hexanoic succinimide ester,
      followed by a reaction with dipeptides. The final coupling reaction was performed
      between the semisynthesized Fmoc-KF hydrolysis product and the C-terminal
      fragment, followed by the deprotection of the Fmoc group. RESULTS: Six KF
      analogues with an addition of an amino acid residue on the N-terminal chain, d
      Val14-isoKF (2), Val13-Val14-isoKF (3), d-Leu14-isoKF (4), d-Pro14-isoKF (5), d
      Phe14-isoKF (6), and 3,4-2F-d-Phe14-isoKF (7) were prepared using semisynthesis
      at the exposed N-terminal chain. CONCLUSIONS: The overall yield of the medication
      was 45%. This approach is economical, efficient and amendable to large-scale
      production while eliminated a nuisance algal bloom. GENERAL SIGNIFICANCE: B.
      pennata blooms are capable of producing KF in good yields. The semisynthesis from
      the natural product produced N-terminal modifications for the construction of
      inexpensive semisynthetic KF libraries.

PMID- 25964071
TI  - Clinical significance of Angiopoietin-1 in Behcet's disease patients with
      vascular involvement.
AB  - Behcet's disease (BD) is a chronic multisystem inflammatory disorder of unclear
      etiology. Vascular inflammation, endothelial dysfunction and angiogenesis may be
      in part responsible for the pathogenesis of BD. Angiopoietin-1 (Ang-1) is a
      recent angiogenic mediator. The aim of the present study was to assess Ang-1 in
      the plasma of BD patients as well as to analyze its association with clinical,
      and laboratory parameters of the disease. The present study included 47 BD
      patients and 30 age- and gender-matched healthy controls. Demographic, clinical,
      disease activity and severity were prospectively assessed. Plasma Ang-1 levels
      were measured using enzyme-linked immunosorbent assay. The plasma level of Ang-1
      in BD patients was significantly lower than healthy controls (p = 0.005). Plasma
      Ang-1 level in patients with vascular affection was significantly lower than
      those without vascular affection (p = 0.045). Levels of Ang-1 showed a
      significant positive correlation with steroid dose. Patients who received
      cyclophosphamide or steroids showed a significant increase in plasma Ang-1 level.
      This was further confirmed by the results of the multivariate analysis. There was
      no significant association between plasma Ang-1 levels and other clinical
      manifestations or disease activity and severity. Plasma Ang-1 levels were
      diminished in our BD patients especially in patients with vascular involvement.
      Larger studies with further investigations of the precise role of Ang-1 in the
      pathogenesis of BD are needed and might lead to novel therapies for the clinical
      management of BD. 

PMID- 25964072
TI  - Impact of spotty calcification on long-term prediction of future
      revascularization: a prospective three-vessel intravascular ultrasound study.
AB  - To date, there are no prospective studies on the relationship between plaque
      characteristics identified by 40 MHz IVUS and future adverse events. This
      prospective study evaluated the relationship between plaque morphology in
      nonculprit nonsignificant lesions, determined by 40 MHz IVUS, and long-term
      clinical outcomes. Consecutively, 45 patients who underwent 3-vessel
      intravascular ultrasound (IVUS) examinations were prospectively enrolled.
      Qualitative and quantitative IVUS analyses including scoring of echogenicity for
      assessment of plaque characterization were performed for each nonsignificant
      nonculprit lesion. The number, the length, the location (superficial or deep),
      and maximum arc were measured for each calcium deposit within plaques. Spotty
      calcification was defined as calcium deposits <90 degrees  and <6 mm in length.
      Primary end point was defined as nonsignificant nonculprit lesion-related
      revascularization (NNLR) during 6 years of follow-up. A total of 163
      nonsignificant nonculprit lesions with mild to moderate stenosis were identified
      on baseline 3-vessel IVUS. Of those 163 lesions, six lesions required NNLR during
      the follow-up period. There were no differences in quantitative IVUS parameters
      including remodeling index, plaque burden, and echogenicity between lesions
      requiring and not requiring NNLR. However, deep spotty calcification was more
      frequently identified in lesions requiring NNLR than in those not requiring NNLR
      (33 vs. 8 %, P = 0.02). Spotty calcium deposits identified by 40 MHz IVUS
      predicted the need for NNLR during a 6-year follow-up period. This finding
      suggests that deep spotty calcium may be a surrogate marker for plaque
      progression and the subsequent need for revascularization in the future. 

PMID- 25964073
TI  - The predictability of renin-angiotensin-aldosterone system factors for clinical
      outcome in patients with acute decompensated heart failure.
AB  - Although counter-regulation between B-type natriuretic peptide (BNP) levels and
      renin-angiotensin-aldosterone system (RAAS) activation in heart failure (HF) has
      been suggested, whether the regulation is preserved in acute decompensated heart
      failure (ADHF) patients remains unclear. This study aimed to determine: (1) the
      relationship between RAAS activation and clinical outcomes in ADHF patients, and
      (2) the relationships between plasma BNP levels and degrees of activation in RAAS
      factors. This study included ADHF patients (n = 103, NYHA3-4, plasma BNP > 200
      pg/ml). We studied the predictability of RAAS factors for cardiovascular events
      and the relationships between plasma BNP levels and the degrees of activation in
      RAAS factors, which were evaluated by plasma renin activity (PRA) and aldosterone
      concentration (PAC). PRA was a strong predictor of cardiovascular (CV) events
      over 1 year, even after accounting for plasma BNP levels (hazard ratio (HR):
      1.04, CI [1.02-1.06], p < 0.01) and medication such as RAAS blockers (HR: 1.03,
      CI [1.01-1.05], p < 0.01), whereas PAC was borderline-significant (univariate
      analysis, p = 0.06). Cut-off value of PRA (5.3 ng/ml/h) was determined by AUC
      curve. Of the enrolled patients, higher PRA was found in 40 % of them. Although
      no correlation between the plasma BNP levels and PRA was found (p = 0.36), after
      adjusting for hemodynamic parameters, eGFR and medication, a correlation was
      found between them (p = 0.01). Elevated RAAS factors were found in a substantial
      number of ADHF patients with high plasma BNP levels in the association with
      hemodynamic state, which predicts poor clinical outcomes. The measurements of
      RAAS factors help to stratify ADHF patients at risk for further CV events. 

PMID- 25964074
TI  - High-sensitivity cardiac troponin T level is associated with angiographic
      complexity of coronary artery disease: a cross-sectional study.
AB  - High levels of high-sensitivity cardiac troponin T (hs-cTnT) are associated with
      coronary artery disease (CAD). The SYNTAX score (SXscore) is an angiographic tool
      used to grade the complexity and extent of CAD. We investigated the relationship
      between hs-cTnT levels and SXscore. We conducted a cross-sectional analysis of
      408 patients who underwent first diagnostic coronary angiography between December
      2011 and December 2012. SXscore was recorded, and serum hs-cTnT levels were
      measured in all patients. The median hs-cTnT level was 0.009 MUg/L. Elevated hs
      cTnT levels (>=0.014 MUg/L) were observed in 136 patients (33 %). Twenty-seven
      patients (7 %) had complex CAD as defined by intermediate or high SXscores. The
      levels of hs-cTnT were significantly higher in patients with high or intermediate
      SXscores than in those with low SXscores (0.044 +/- 0.055 vs. 0.018 +/- 0.058
      MUg/L, p = 0.03). Multivariate analysis identified hs-cTnT level, and diabetes
      mellitus as independent predictors for complex CAD. The adjusted odds ratio of hs
      cTnT level for predicting complex CAD was 2.86 (95 % confidence interval 1.90
      4.45, p < 0.0001). Predictive value of the adjusted area under the receiver
      operating characteristic curve for complex CAD significantly improved after
      inclusion of the hs-cTnT (C statistic, 0.882 vs. 0.784). Measurement of serum hs
      cTnT level has an important role in the risk stratification of patients who have
      a plan for diagnostic coronary angiography. In patients with clinically stable
      angina pectoris, slightly elevated hs-cTnT levels may indicate the presence of
      complex CAD. 

PMID- 25964070
TI  - Rosiglitazone treatment and cardiovascular disease in the Veterans Affairs
      Diabetes Trial.
AB  - AIMS: To evaluate the relationship between patterns of rosiglitazone use and
      cardiovascular (CV) outcomes in the Veterans Affairs Diabetes Trial (VADT).
      METHODS: Time-dependent survival analyses, case-control and 1 : 1 propensity
      matching approaches were used to examine the relationship between patterns of
      rosiglitazone use and CV outcomes in the VADT, a randomized controlled study that
      assessed the effect of intensive glycaemic control on CV outcomes in 1791
      patients with type 2 diabetes (T2D) whose mean age was 60.4 +/- 9 years.
      Participants were recruited between 1 December 2000 and 31 May 2003, and were
      followed for 5-7.5 years (median 5.6) with a final visit by 31 May 2008.
      Rosiglitazone (4 mg and 8 mg daily) was initiated per protocol in both the
      intensive-therapy and standard-therapy groups. Main outcomes included a composite
      CV outcome, CV death and myocardial infarction (MI). RESULTS: Both daily doses of
      rosiglitazone were associated with lower risk for the primary composite CV
      outcome [4 mg: hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.49-0.81 and
      8 mg: HR 0.60, 95% CI 0.49-0.75] after adjusting for demographic and clinical
      covariates. A reduction in CV death was also observed (HR 0.25, p < 0.001, for
      both 4 and 8 mg/day rosiglitazone); however, the effect on MI was less evident
      for 8 mg/day and not significant for 4 mg/day. CONCLUSIONS: In older patients
      with T2D the use of rosiglitazone was associated with decreased risk of the
      primary CV composite outcome and CV death. Rosiglitazone use did not lead to a
      higher risk of MI.

PMID- 25964076
TI  - Enhancing radiolytic stability upon concentration of tritium-labeled
      pharmaceuticals utilizing centrifugal evaporation.
AB  - Tritium radiopharmaceuticals are often used in drug development because of their
      desirable specific activity. The inherent instability of these radioactive
      tracers often leads to a requirement to purify prior to use. Purification
      methodologies such as preparative chromatography and solid/liquid extractions
      often utilize water as a solvent, which is not suitable for long-term storage and
      necessitates removal. Rotary evaporation has traditionally been utilized for the
      removal of this unwanted solvent, however, this method has been shown to lead to
      decomposition of the tritium species in some cases. Centrifugal evaporation is a
      milder concentration method which has been demonstrated to effectively remove
      solvents. In this study, we show that centrifugal evaporation leads to effective
      concentration of tritium samples without the decomposition typically observed by
      rotary evaporation. 

PMID- 25964075
TI  - Activating enhancer binding protein 2 epsilon (AP-2epsilon)-deficient mice
      exhibit increased matrix metalloproteinase 13 expression and progressive
      osteoarthritis development.
AB  - INTRODUCTION: The transcription factor activating enhancer binding protein 2
      epsilon (AP-2epsilon) was recently shown to be expressed during chondrogenesis as
      well as in articular chondrocytes of humans and mice. Furthermore, expression of
      AP-2epsilon was found to be upregulated in affected cartilage of patients with
      osteoarthritis (OA). Despite these findings, adult mice deficient for AP-2epsilon
      (Tfap2e(-/-)) do not exhibit an obviously abnormal cartilaginous phenotype. We
      therefore analyzed embryogenesis of Tfap2e(-/-) mice to elucidate potential
      transient abnormalities that provide information on the influence of AP-2epsilon
      on skeletal development. In a second part, we aimed to define potential
      influences of AP-2epsilon on articular cartilage function and gene expression, as
      well as on OA progression, in adult mice. METHODS: Murine embryonic development
      was accessed via in situ hybridization, measurement of skeletal parameters and
      micromass differentiation of mesenchymal cells. To reveal discrepancies in
      articular cartilage of adult wild-type (WT) and Tfap2e(-/-) mice, light and
      electron microscopy, in vitro culture of cartilage explants, and quantification
      of gene expression via real-time PCR were performed. OA was induced via surgical
      destabilization of the medial meniscus in both genotypes, and disease progression
      was monitored on histological and molecular levels. RESULTS: Only minor
      differences between WT and embryos deficient for AP-2epsilon were observed,
      suggesting that redundancy mechanisms effectively compensate for the loss of AP
      2epsilon during skeletal development. Surprisingly, though, we found matrix
      metalloproteinase 13 (Mmp13), a major mediator of cartilage destruction, to be
      significantly upregulated in articular cartilage of adult Tfap2e(-/-) mice. This
      finding was further confirmed by increased Mmp13 activity and extracellular
      matrix degradation in Tfap2e(-/-) cartilage explants. OA progression was
      significantly enhanced in the Tfap2e(-/-) mice, which provided evidence for in
      vivo relevance. This finding is most likely attributable to the increased basal
      Mmp13 expression level in Tfap2e(-/-) articular chondrocytes that results in a
      significantly higher total Mmp13 expression rate during OA as compared with the
      WT. CONCLUSIONS: We reveal a novel role of AP-2epsilon in the regulation of gene
      expression in articular chondrocytes, as well as in OA development, through
      modulation of Mmp13 expression and activity.

PMID- 25964077
TI  - Gender differences in the longitudinal associations of depressive symptoms and
      leisure-time physical activity with cognitive decline in >=57year-old Taiwanese.
AB  - OBJECTIVE: This study investigates the role of gender in the associations of long
      term depressive symptoms and leisure-time physical activity (LTPA) with the risk
      of cognitive decline in elderly Taiwanese. METHOD: We analyzed 3679 subjects (age
      >=57) in the 2003 and 2007 datasets of the Taiwan Longitudinal Survey on Aging,
      of which data were collected via face-to-face interviews by trained interviewers.
      We excluded proxy respondents. Multivariable logistic regression analysis
      examined the associations of long-term depressive symptoms (increased symptoms:
      CES-D10 scores from <10 to >=10; decreased symptoms: from >=10 to <10) and LTPA
      (frequency, duration, and intensity) with cognitive decline (a decrease of two or
      more SPMSQ scores). RESULTS: Women had significant higher percentages of
      cognitive impairment, compared to men, at the baseline (5.9 vs. 1.5%;
      chi(2)=51.24, p<0.001) and end-point (10.8 vs. 5.2%;chi(2)=39.5, p<0.001). Men
      with long-term depressive symptoms had 5.28 greater odds of cognitive decline
      (OR=5.28, 95%CI=2.84-9.82, p<0.001) and men with increased depressive symptoms
      had 2.09 greater odds (2.09, 1.24-3.51, p=0.006). No such association was
      observed in women. Men with consistently high LTPA had 65% (0.35, 0.19-0.65,
      p=0.001) and women with increased LTPA had 43% (0.57, 0.34-0.93, p=0.024)
      reduction in odds of developing cognitive decline. CONCLUSION: We found gender
      differences in the longitudinal association between depressive symptoms and
      cognitive decline. Long-term LTPA may loosen the association between long-term
      depressive symptoms and cognitive decline. These findings are useful in the
      identification of vulnerable elderly in the Taiwanese population and public
      health interventions should focus on assisting their cognitive aging.

PMID- 25964078
TI  - Physical activity and healthy eating environmental audit tools in youth care
      settings: A systematic review.
AB  - BACKGROUND: There is a growing interest in evaluating the physical activity (PA)
      and healthy eating (HE) policy and practice environment characteristics in
      settings frequented by youth (<=18years). OBJECTIVE: This review evaluates the
      measurement properties of audit tools designed to assess PA and HE policy and
      practice environment characteristics in settings that care for youth (e.g.,
      childcare, school, afterschool, summer camp). METHOD: Three electronic databases,
      reference lists, educational department and national health organizations' web
      pages were searched between January 1980 and February 2014 to identify tools
      assessing PA and/or HE policy and practice environments in settings that care for
      youth (<=18years). RESULTS: Sixty-five audit tools were identified of which 53
      individual tools met the inclusion criteria. Thirty-three tools assessed both the
      PA and HE domains, 6 assessed the PA domain and 14 assessed the HE domain solely.
      The majority of the tools were self-assessment tools (n=40), and were developed
      to assess the PA and/or HE environment in school settings (n=33), childcare
      (n=12), and after school programs (n=4). Four tools assessed the community at
      large and had sections for assessing preschool, school and/or afterschool
      settings within the tool. The majority of audit tools lacked validity and/or
      reliability data (n=42). Inter-rater reliability and construct validity were the
      most frequently reported reliability (n=7) and validity types (n=5). CONCLUSIONS:
      Limited attention has been given to establishing the reliability and validity of
      audit tools for settings that care for youth. Future efforts should be directed
      towards establishing a strong measurement foundation for these important
      environmental audit tools.

PMID- 25964079
TI  - Long noncoding RNA DANCR increases stemness features of hepatocellular carcinoma
      by derepression of CTNNB1.
AB  - Tumor cells with stemness (stem-cell) features contribute to initiation and
      progression of hepatocellular carcinoma (HCC), but involvement of long noncoding
      RNAs (lncRNAs) remains largely unclear. Genome-wide analyses were applied to
      identify tumor-associated lncRNA-DANCR. DANCR expression level and prognostic
      values of DANCR were assayed in two HCC cohorts (China and Korea, n = 135 and
      223). Artificial modulation of DANCR (down- and overexpression) was done to
      explore the role of DANCR in tumorigenesis and colonization, and tumor-bearing
      mice were used to determine therapeutic effects. We found that lncRNA-DANCR is
      overexpressed in stem-like HCC cells, and this can serve as a prognostic
      biomarker for HCC patients. Experiments showed that DANCR markedly increased
      stemness features of HCC cells to promote tumorigenesis and intra-/extrahepatic
      tumor colonization. Conversely, DANCR knockdown attenuated the stem-cell
      properties and in vivo interference with DANCR action led to decreased tumor cell
      vitality, tumor shrinkage, and improved mouse survival. Additionally, we found
      that the role of DANCR relied largely on an association with, and regulation of,
      CTNNB1. Association of DANCR with CTNNB1 blocked the repressing effect of
      microRNA (miR)-214, miR-320a, and miR-199a on CTNNB1. This observation was
      confirmed in vivo, suggesting a novel mechanism of tumorigenesis involving
      lncRNAs, messenger RNAs, and microRNAs. CONCLUSIONS: These studies reveal a
      significance and mechanism of DANCR action in increasing stemness features and
      offer a potential prognostic marker and a therapeutic target for HCC.

PMID- 25964080
TI  - NJK14013, a novel synthetic estrogen receptor-alpha agonist, exhibits estrogen
      receptor-independent, tumor cell-specific cytotoxicity.
AB  - Estrogens act through interactions with estrogen receptors (ERs) to play diverse
      roles in various pathophysiological conditions. A number of synthetic selective
      estrogen receptor modulators (SERMs), such as tamoxifen and raloxifene, have been
      developed and used to treat ER-related diseases, including breast cancer and
      osteoporosis. Here, we identified a novel compound, bis(4-hydroxyphenyl)methanone
      O-isopentyl oxime, designated NJK14013, as an ER agonist. NJK14013 activated ER
      dependent transcription in a concentration-dependent manner, while suppressing
      androgen receptor-dependent transcriptional activity. It induced the activation
      related phosphorylation of ER and enhanced the transcription of growth regulation
      by estrogen in breast cancer 1 (GREB1), further supporting its ER-stimulating
      activity. NJK14013 exerted anti-proliferative effects on various cancer cell
      lines, including an ER-negative breast cancer cell line, suggesting that it is
      capable of suppressing the growth of cancer cells independent of its ER
      modulating activity. In addition, NJK14013 treatment resulted in significant
      apoptotic death of MCF7 and Ishikawa cancer cells, but did not induce apoptosis
      in non-cancer human umbilical vein endothelial cells. Collectively, our findings
      demonstrate that NJK14013 is a novel SERM that can activate ER-mediated
      transcription in MCF7 cells and suppress the proliferation of various cancer
      cells, including breast cancer cells and endometrial cancer cells. These results
      suggest that NJK14013 has potential as a novel SERM for anticancer or hormone
      replacement therapy with reduced risk of carcinogenesis.

PMID- 25964081
TI  - Can Computed Tomography-Assessed Right-Sided Ventricular Dysfunction Predict
      Mortality in Hemodynamically Stable Pulmonary Embolism?

PMID- 25964082
TI  - The Long-Term Use of Warfarin Among Atrial Fibrillation Patients Discharged From
      an Emergency Department With a Warfarin Prescription.
AB  - STUDY OBJECTIVE: The optimal timing to begin stroke prevention therapy in
      patients being discharged from an emergency department (ED) with atrial
      fibrillation is not known. We determined whether eligible patients who were
      provided with an ED prescription for oral anticoagulation had better rates of
      long-term anticoagulation use than eligible patients who were referred to their
      primary care provider for further care. METHODS: As part of a historical cohort
      study, in this planned substudy we abstracted data from patient charts with a
      primary diagnosis of atrial fibrillation from 24 EDs between April 1, 2008, and
      March 31, 2009. In the current study, discharged patients aged 65 years and older
      who had a CHADS2 score greater than or equal to 2 and a HAS-BLED score less than
      3, with no history of falls and who were not receiving oral anticoagulation when
      they presented to the ED, were included. We compared the frequency of warfarin
      use at 6 months and 1 year after ED discharge for patients who were given a
      prescription for warfarin before they left the ED to those who were not. RESULTS:
      Among 137 qualifying patients, 33 (24.1%) were provided with a warfarin
      prescription before discharge from the ED. At 6 months, 25 of the 33 were still
      receiving warfarin, compared with 34 of 104 among the patients who were not given
      an ED prescription (absolute difference, 43.1%; 95% confidence interval [CI] 23.8
      to 57.2). At 1 year, 75.8% versus 35.6% (absolute difference, 40.2%; 95% CI 20.9
      to 54.4) were receiving warfarin, respectively. Among the patients who filled a
      prescription for warfarin, the mean number of days from ED discharge until a
      warfarin prescription was filled was 6.0 (SD 21.3) for patients who were provided
      with an ED prescription compared with 205 (SD 377) for those who were not.
      CONCLUSION: Among ED patients who met criteria for guideline-recommended use of
      stroke prevention therapy, those who received an initial prescription in the ED
      had a higher frequency of long-term warfarin use than those for whom the decision
      to initiate therapy was referred to another care provider.

PMID- 25964083
TI  - What Is the Time to Muscle Relaxation After Intramuscular Administration of
      Neuromuscular Blockers?

PMID- 25964084
TI  - The US Office of the National Coordinator for Health Information Technology:
      Progress and Promise for the Future at the 10-Year Mark.
AB  - In April 2004, President Bush signed Executive Order 13335, which called for the
      establishment of the Office of the National Coordinator for Health Information
      Technology (ONC) within the US Department of Health and Human Services. The
      President charged ONC with the critical responsibility of ensuring that every
      American had access to his or her electronic health information and establishing
      connectivity of health information technology.

PMID- 25964085
TI  - Injury Severity Score Inflation Resulting From Pan-Computed Tomography in
      Patients With Blunt Trauma.
AB  - STUDY OBJECTIVE: All articles that demonstrate a mortality benefit from liberal
      pan-computed tomography (CT) use in patients with blunt trauma have relied on
      Injury Severity Score (ISS) to control for morbidity. This mortality benefit may
      be artifact, the result of an increased use of a sensitive diagnostic modality
      rather than a true benefit. We quantify the magnitude of ISS inflation in
      patients with blunt trauma who are undergoing routine pan-CT compared with
      patients who receive more selective scanning. METHODS: This study re-analyzes
      data collected from a previous study of pan-CT use in patients with blunt trauma
      in which surveyed emergency physicians prospectively indicated which portion of a
      pan-CT they wished to obtain. The trauma surgeons who jointly managed all
      patients in this study ultimately decided which CTs to obtain. We recalculated
      the ISS excluding injuries found on the undesired CT scans that did not lead to a
      predefined set of critical actions and compared original and recalculated ISS.
      RESULTS: There were 701 study subjects who received a total of 2,615 scans. Of
      these, there were 992 undesired scans. Ninety-nine of the obtained undesired
      scans, performed in 92 patients, had noncritical abnormalities. The original ISS
      for these 92 patients was 10 (IQR 5, 18); the recalculated ISS was 5
      (interquartile range 1, 10), a 50% decrease. CONCLUSION: Although the median ISS
      for our study was lower than that of previous studies claiming a mortality
      benefit, ISS inflation appears to be a real phenomenon and may confound studies
      that use ISS to control for morbidity.

PMID- 25964086
TI  - Juglone prevents metabolic endotoxemia-induced hepatitis and neuroinflammation
      via suppressing TLR4/NF-kappaB signaling pathway in high-fat diet rats.
AB  - Juglone as a natural production mainly extracted from green walnut husks of
      Juglans mandshurica has been defined as the functional composition among a series
      of compounds. It showed powerful protective effect in various diseases by
      inhibiting inflammation and tumor cells growth. However, studies on its anti
      inflammatory effect based on high-fat diet-induced hepatitis and
      neuroinflammation are still not available. In this regard, we first investigated
      whether juglone suppresses high-fat diet-stimulated liver injury, hypothalamus
      inflammation and underlying mechanisms by which they may recover them. SD rats
      were orally treated with or without high-fat diet, 0.25 mg/kg or 1 mg/kg juglone
      for 70 days. Subsequently, blood, hypothalamus and liver tissue were collected
      for different analysis. Also, the primary astrocytes were isolated and used to
      analyze the inhibitory effect of juglone in vitro. Analysis of inflammatory
      cytokines declared that the inhibition of TNF-alpha, IL-1beta and IL-6 could be
      carried by juglone in response to high-fat diet rats. Meanwhile, TLR4 expression
      and NF-kappa activity also have been confirmed to be the key link in the
      development of hepatitis and nerve inflammation. The activation was significantly
      suppressed in treatment group as compared with model. These results indicated
      that juglone prevents high-fat diet-induced liver injury and nerve inflammation
      in mice through inhibition of inflammatory cytokine secretion, NF-kappa B
      activation and endotoxin production. 

PMID- 25964087
TI  - The A- and B-type muscarinic acetylcholine receptors from Drosophila melanogaster
      couple to different second messenger pathways.
AB  - Muscarinic acetylcholine receptors (mAChRs) are G protein-coupled receptors
      (GPCRs) that are activated by the agonists acetylcholine and muscarine and
      blocked by several antagonists, among them atropine. In mammals five mAChRs (m1
      m5) exist of which m1, m3, and m5 are coupled to members of the Gq/11 family and
      m2 and m4 to members of the Gi/0 family. We have recently shown that Drosophila
      melanogaster and other arthropods have two mAChRs, named A and B, where the A
      type has the same pharmacology as the mammalian mAChRs, while the B-type has a
      very low affinity to muscarine and no affinity to classical antagonists such as
      atropine. Here, we find that the D. melanogaster A-type mAChR is coupled to Gq/11
      and D. melanogaster B-type mAChR to Gi/0. Furthermore, by comparing the second
      and third intracellular loops of all animal mAChRs for which the G protein
      coupling has been established, we could identify several amino acid residues
      likely to be specific for either Gq/11 or Gi/0 coupling. Using these hallmarks
      for specific mAChR G protein interaction we found that all protostomes with a
      sequenced genome have one mAChR coupled to Gq/11 and one to four mAChRs coupled
      to Gi/0. Furthermore, in protostomes, probably all A-type mAChRs are coupled to
      Gq/11 and all B-type mAChRs to G0/i. 

PMID- 25964088
TI  - Pathological characterization of pachydermia in pachydermoperiostosis.
AB  - Pachydermoperiostosis is a rare hereditary disease, which presents with the
      cutaneous manifestations of pachydermia and cutis verticis gyrata. Histological
      findings in pachydermia frequently include dermal edema, mucin deposition,
      elastic fiber degeneration, dermal fibrosis and adnexal hyperplasia. However, the
      severity of these findings varies between clinical reports, and a systematic
      multiple-case clinicopathological correlative analysis has not been performed to
      date. In the present study, we reviewed the skin biopsy specimens obtained from
      the pachydermia of six pachydermoperiostosis patients. The severity of the
      characteristic histological features was semiquantitatively evaluated and
      correlated with the grade of pachydermia. Dermal edema, mucin deposition and
      elastic fiber degeneration were observed in all cases. Patients with severe
      pachydermia had sebaceous gland hyperplasia and fibrosis. These results suggest
      that the triad of mucin deposition, dermal edema and elastic fiber degeneration
      are found from very early stage pachydermia, and could be considered diagnostic
      findings. To ensure an earlier diagnosis of pachydermoperiostosis, a biopsy
      should be taken when a patient has grade 1 pachydermia to determine the presence
      of this histological triad. 

PMID- 25964089
TI  - A new HLA-B*15 allele, HLA-B*15:263, identified in a Korean individual.
AB  - HLA-B*15:263 differs from HLA-B*15:18:01 by a single nucleotide exchange at
      position 824, C>G (codon 251 TCT>TGT). 

PMID- 25964090
TI  - A molecular mechanism for the origin of a key evolutionary innovation, the bird
      beak and palate, revealed by an integrative approach to major transitions in
      vertebrate history.
AB  - The avian beak is a key evolutionary innovation whose flexibility has permitted
      birds to diversify into a range of disparate ecological niches. We approached the
      problem of the mechanism behind this innovation using an approach bridging
      paleontology, comparative anatomy, and experimental developmental biology. First,
      we used fossil and extant data to show the beak is distinctive in consisting of
      fused premaxillae that are geometrically distinct from those of ancestral
      archosaurs. To elucidate underlying developmental mechanisms, we examined
      candidate gene expression domains in the embryonic face: the earlier frontonasal
      ectodermal zone (FEZ) and the later midfacial WNT-responsive region, in birds and
      several reptiles. This permitted the identification of an autapomorphic median
      gene expression region in Aves. To test the mechanism, we used inhibitors of both
      pathways to replicate in chicken the ancestral amniote expression. Altering the
      FEZ altered later WNT responsiveness to the ancestral pattern. Skeletal
      phenotypes from both types of experiments had premaxillae that clustered
      geometrically with ancestral fossil forms instead of beaked birds. The palatal
      region was also altered to a more ancestral phenotype. This is consistent with
      the fossil record and with the tight functional association of avian premaxillae
      and palate in forming a kinetic beak. 

PMID- 25964091
TI  - FCRL regulation in innate-like B cells.
AB  - Coelomic cavity-derived B-1 and splenic marginal zone (MZ) B lymphocytes play
      principal roles in frontline host protection at homeostasis and during primary
      humoral immune responses. Although they share many features that enable rapid and
      broad-based defense against pathogens, these innate-like subsets have disparate B
      cell receptor (BCR) signaling features. Members of the Fc receptor-like (FCRL)
      family are preferentially expressed by B cells and possess tyrosine-based
      immunoregulatory function. An unusual characteristic of many of these cell
      surface proteins is the presence of both inhibitory (ITIM) and activating (ITAM
      like) motifs in their cytoplasmic tails. In mice, FCRL5 is a discrete marker of
      splenic MZ and peritoneal B-1 B cells and has both ITIM and ITAM-like sequences.
      Recent work explored its signaling properties and identified that FCRL5
      differentially influences innate-like BCR function. Closer scrutiny of these
      differences disclosed the ability of FCRL5 to counter-regulate BCR activation by
      recruiting SHP-1 and Lyn to its cytoplasmic motifs. Furthermore, the disparity in
      FCRL5 regulation between MZ and B-1 B cells correlated with relative
      intracellular concentrations of SHP-1. These findings validate and extend our
      understanding of the unique signaling features in innate-like B cells and provide
      new insight into the complexity of FCRL modulation. 

PMID- 25964092
TI  - Activation of M3 muscarinic receptor by acetylcholine promotes non-small cell
      lung cancer cell proliferation and invasion via EGFR/PI3K/AKT pathway.
AB  - Acetylcholine (ACh), which can be synthesized and secreted by cancer cells, has
      been reported to play an important role in tumor progression. ACh acts its role
      through activation of its receptors, muscarinic receptor (mAChR), and nicotinic
      receptor (nAChR). As a member of mAChR, M3 muscarinic receptor (M3R) is often
      highly expressed in many cancers. Activation of M3R by ACh participates in the
      proliferation, differentiation, transformation, and carcinogenesis of cancer.
      However, the effect of M3R activation on non-small cell lung cancer (NSCLC)
      remains unclear. Here, our study found that ACh dose-dependently promoted the
      proliferation, invasion, and migration of NSCLC cells. After silencing of M3R,
      the biological functions of ACh in NSCLC cells were greatly attenuated.
      Furthermore, ACh stimulation increased the production of IL-8 and time
      dependently induced the activation of EGFR, PI3K, and AKT through M3R. In
      addition, ACh stimulated the activation of PI3K and AKT via EGFR activity, and
      blocking of PI3K/AKT pathway by special inhibitor LY294002 suppressed the ACh
      mediated proliferation, invasion, and migration of NSCLC cells. Taken together,
      these findings indicate that activation of M3R by ACh enhances the proliferation,
      invasion, and migration of NSCLC cells. ACh-induced activation of EGFR/PI3K/AKT
      pathway and subsequent IL-8 upregulation may be one of the important mechanisms
      of M3R function. Thus, M3R could be a potential therapeutic target for the
      treatment of NSCLC.

PMID- 25964093
TI  - Overexpression of chromosome 14 open reading frame 166 correlates with disease
      progression and poorer prognosis in human NPC.
AB  - Chromosome 14 open reading frame 166 (c14orf166) contributes to regulation of
      centrosome architecture, transcription initiation, and RNA elongation and
      processing. However, the role of c14orf166 in human cancer remains unclear. This
      study aimed to investigate the expression and clinicopathological significance of
      c14orf166 in nasopharyngeal carcinoma (NPC). Real-time PCR and Western blotting
      analyses were employed to examine c14orf166 expression in immortalized primary
      nasopharyngeal epithelial cells (NP69), six NPC cell lines, three paired tumor
      samples and the adjacent noncancerous tissues from the same patients, and three
      additional tumor samples. Immunohistochemistry was performed to examine c14orf166
      protein expression in archived paraffin-embedded tumor samples from 109 patients
      with clinicopathologically confirmed NPC. The association of c14orf166 expression
      with clinicopathological features and survival outcomes was assessed. C14orf166
      messenger RNA and protein expression were upregulated in NPC cell lines and human
      tumor tissues compared to NP69 cells and noncancerous tissue samples,
      respectively. Immunohistochemical analyses revealed 104/109 (95.4 %) of the NPC
      tissue samples expressed c14orf166. High expression of c14orf166 (cutoff score
      >6) was significantly associated with gender (P = 0.016), clinical stage (P =
      0.010), T classification (P = 0.013), N classification (P = 0.029), distant
      metastasis (P < 0.001), vital status (P = 0.001), and treatment method (P =
      0.028; chi-square test). High c14orf166 expression was associated with
      significantly shorter overall survival (OS) and disease-free survival (DFS) than
      low c14orf166 expression. Multivariate analysis revealed c14orf166 was an
      independent prognostic indicator of OS and DFS in all patients (P = 0.046, P =
      0.006) and was associated with poor OS and DFS in the subgroups with advanced
      clinical stage (P = 0.037, P = 0.001), lymph node metastasis (P = 0.001, P <
      0.001), and T3-T4 disease (P = 0.005, P = 0.001), respectively. C14orf166 is
      overexpressed and may represent a novel prognostic factor in NPC.

PMID- 25964094
TI  - Pulmonary hypertension in non-transfusion-dependent thalassemia: Correlation with
      clinical parameters, liver iron concentration, and non-transferrin-bound iron.
AB  - BACKGROUND: Pulmonary hypertension is a major cardiac complication in non
      transfusion-dependent thalassemia (NTDT). Several clinical and laboratory
      parameters, including iron overload, have been shown to have a positive
      correlation with the incidence of pulmonary hypertension. Non-transferrin-bound
      iron (NTBI) is a form of free-plasma iron that is a good indicator of iron
      overload. OBJECTIVES: The aim of this study was to determine the prevalence of
      pulmonary hypertension in patients with NTDT and to investigate its correlation
      with the clinical parameters, liver iron concentration (LIC) and NTBI. METHODS:
      Patients with NTDT were evaluated using echocardiography, and magnetic resonance
      imaging for cardiac T2* and LIC. Pulmonary hypertension was defined as peak
      tricuspid regurgitation velocity >=2.9 m/s measured using trans-thoracic
      echocardiography. Clinical parameters and the status of iron overload as
      determined by LIC, serum ferritin, and NTBI level were evaluated for their
      association with pulmonary hypertension. RESULTS: Of 76 NTDT patients, mean age
      23.7 +/- 8.5 years, seven patients (9.2%) had pulmonary hypertension. Previous
      splenectomy (71.4 vs. 24.6%, P-value 0.019), higher cumulative red blood cell
      (RBC) transfusions (received >=10 RBC transfusions 85.7 vs. 33.3%, P-value
      0.011), higher nucleated RBCs (353 +/- 287 vs. 63 +/- 160/100 white blood cells,
      P-value <0.001), and a high NTBI level (5.7 +/- 3.0 vs. 3.3 +/- 2.8 umol/l, P
      value 0.034) were associated with pulmonary hypertension. There was no
      significant correlation between LIC or serum ferritin and pulmonary hypertension.
      CONCLUSION: Pulmonary hypertension in NTDT is common, and is associated with
      splenectomy and its related factors. NTBI level shows a significant correlation
      with pulmonary hypertension.

PMID- 25964095
TI  - Rats demonstrate helping behavior toward a soaked conspecific.
AB  - Helping behavior is a prosocial behavior whereby an individual helps another
      irrespective of disadvantages to him or herself. In the present study, we
      examined whether rats would help distressed, conspecific rats that had been
      soaked with water. In Experiment 1, rats quickly learned to liberate a soaked
      cagemate from the water area by opening the door to allow the trapped rat into a
      safe area. Additional tests showed that the presentation of a distressed cagemate
      was necessary to induce rapid door-opening behavior. In addition, it was shown
      that rats dislike soaking and that rats that had previously experienced a soaking
      were quicker to learn how to help a cagemate than those that had never been
      soaked. In Experiment 2, the results indicated that rats did not open the door to
      a cagemate that was not distressed. In Experiment 3, we tested behavior when rats
      were forced to choose between opening the door to help a distressed cagemate and
      opening a different door to obtain a food reward. Irrespective of how they
      learned to open the door, in most test trials, rats chose to help the cagemate
      before obtaining a food reward, suggesting that the relative value of helping
      others is greater than the value of a food reward. These results suggest that
      rats can behave prosocially and that helper rats may be motivated by empathy-like
      feelings toward their distressed cagemate. 

PMID- 25964096
TI  - Chimpanzees strategically manipulate what others can see.
AB  - Humans often strategically manipulate the informational access of others to their
      own advantage. Although chimpanzees know what others can and cannot see, it is
      unclear whether they can strategically manipulate others' visual access. In this
      study, chimpanzees were given the opportunity to save food for themselves by
      concealing it from a human competitor and also to get more food for themselves by
      revealing it to a human cooperator. When knowing that a competitor was
      approaching, chimpanzees kept more food hidden (left it covered) than when
      expecting a cooperator to approach. When the experimenter was already at the
      location of the hidden food, they actively revealed less food to the competitor
      than to the cooperator. They did not actively hide food (cover up food in the
      open) from the competitor, however. Chimpanzees thus strategically manipulated
      what another could see in order to maximize their payoffs and showed their
      ability to plan for future situations. 

PMID- 25964097
TI  - Preclinical and clinical development of an anti-kappa free light chain mAb for
      multiple myeloma.
AB  - Monoclonal antibodies (mAb) have had tremendous success in treating a variety of
      cancers over the past twenty years. Yet despite their widespread clinical use,
      which includes treatments for haematological malignancies, there are still no
      approved mAb therapies for multiple myeloma (MM). This is likely to change within
      the next few years with a number of mAb therapies being assessed in late stage
      clinical trials, most notably, the anti-CS-1 mAb, elotuzumab, and the anti-CD38
      mAb, daratumumab, which are currently being evaluated in Phase III clinical
      trials for MM. In this review, we will discuss the preclinical and clinical
      development of MDX-1097, a Phase II candidate which targets cell membrane
      associated kappa immunoglobulin free light chains expressed on the surface of MM
      cells. 

PMID- 25964098
TI  - Delayed administration of allogeneic cardiac stem cell therapy for acute
      myocardial infarction could ameliorate adverse remodeling: experimental study in
      swine.
AB  - BACKGROUND: The optimal timing of cardiac stem cells administration is still
      unclear. We assessed the safety of same-day and delayed (one week) delivery and
      the possible influence of the timing on the therapeutic outcomes of allogeneic
      porcine cardiac stem cells administration after acute myocardial infarction in a
      closed-chest ischemia-reperfusion model. METHODS: Female swine surviving 90 min
      occlusion of the mid left anterior descending coronary artery received an
      intracoronary injection of 25x10(6) porcine cardiac stem cells either two hours
      (n = 5, D0) or 7 days (n = 6, D7) after reperfusion. Controls received
      intracoronary injection of vehicle on day 7 (n = 6, CON). Safety was defined in
      terms of absence of major cardiac events, changes to the ECG during injection,
      post-administration coronary flow assessed using the TIMI scale and cardiac
      troponin I determination after the intervention. Cardiac Magnetic Resonance was
      performed for morphological and functional assessment prior to infarction, before
      injection (D7 and CON groups only), at one and 10 weeks. Samples were taken from
      the infarct and transition areas for pathological examination. RESULTS: No major
      adverse cardiac events were seen during injection in any group. Animals receiving
      the therapy on the same day of infarction (D0 group) showed mild transient ST
      changes during injection (n = 4) and, in one case, slightly compromised coronary
      flow (TIMI 2). Cardiac function parameters and infarct sizes were not
      significantly different between groups, with a trend towards higher ejection
      fraction in the treated groups. Ventricular volumes indexed to body surface area
      increased over time in control animals, and decreased by the end of the study in
      animals receiving the therapy, significantly so when comparing End Diastolic
      Volume between CON and D7 groups (CON: 121.70 ml/m(2) +/- 26.09 ml/m(2), D7:
      98.71 ml/m(2) +/- 8.30 ml/m(2), p = 0.037). The treated groups showed less
      organization of the collagenous scar, and a significantly (p = 0.019) higher
      amount of larger, more mature vessels at the infarct border. CONCLUSIONS: The
      intracoronary injection of 25x10(6) allogeneic cardiac stem cells is generally
      safe, both early and 7 days after experimental infarction, and alleviates
      myocardial dysfunction, with a greater limitation of left ventricular remodeling
      when performed at one week.

PMID- 25964099
TI  - Oligodendroglial maldevelopment in the cerebellum after postnatal hyperoxia and
      its prevention by minocycline.
AB  - According to recent research, brain injury after premature birth often includes
      impaired growth of the cerebellum. However, causes of cerebellar injury in this
      population are poorly understood. In this study, we analyzed whether postnatal
      hyperoxia perturbs white matter development of the cerebellum, and whether
      cerebellar glial damage can be prevented by minocycline. We used a hyperoxia
      model in neonatal rats providing 24 h exposure to fourfold increased oxygen
      concentration (80% O2) from P6 to P7, followed by recovery in room air until P9,
      P11, P15, P30. Injections with minocycline were performed at the beginning and 12
      h into hyperoxia exposure. Hyperoxia induced oxidative stress in the cerebellum
      at P7 as evidenced by increased nitrotyrosine concentrations. Numbers of
      proliferating, NG2+Ki67+ oligodendroglial precursor cells were decreased at P7
      after hyperoxia and at P11 following recovery in room air. Numbers of mature,
      CC1+ oligodendrocytes were diminished in recovering hyperoxia rats, and myelin
      basic protein expression was still decreased at P30. Electron microscopy analysis
      of myelinated fibers at P30 revealed thinner myelin sheath after hyperoxia. Long
      term injury of the cerebellum by neonatal hyperoxia was confirmed by reduced
      volumes in MRI measurements at P30. In response to 80% O2, expression of platelet
      derived growth factor (PDGF)-A was largely reduced in cerebellar tissue and also
      in cultured cerebellar astrocytes. Treatment with minocycline during hyperoxia
      prevented oxidative stress, attenuated oligodendroglial injury, and improved
      astroglial PDGF-A levels. In conclusion, early hyperoxia causes white matter
      damage in the cerebellum with astroglial dysfunction being involved, and both can
      be prevented by treatment with minocycline. Neonatal exposure to hyperoxia causes
      hypomyelination of the cerebellum. Reduced astroglial growth factor production
      but not microglial inflammation seems to contribute to oligodendroglial damage,
      and minocycline rescues oligodendroglia development in the cerebellum after
      hyperoxia.

PMID- 25964100
TI  - Identification of anti-thrombopoietin receptor antibody in prolonged
      thrombocytopenia after allogeneic hematopoietic stem cell transplantation treated
      successfully with eltrombopag.
AB  - A 55-year-old female with stage IVA follicular lymphoma in third complete
      remission underwent allogeneic peripheral blood stem cell transplantation.
      Neutrophil engraftment was achieved on day +18; however, platelet counts remained
      below 10 * 10(3)/uL, necessitating transfusions twice a week for more than 3
      months. Bone marrow showed a decreased number of megakaryocytes with
      hypolobulated nuclei. No graft versus host disease, viral infection, or disease
      relapse was observed. Furthermore, severe thrombocytopenia below 5.0 * 10(3)/uL
      refractory to transfusion appeared on day +240 after influenza virus infection.
      Treatments with intravenous immunoglobulin, romiplostim, and rituximab were
      administered without any recovery. Subsequently, eltrombopag was initiated on day
      +443, after which platelet counts rose gradually and continued to rise above 20 *
      10(3)/uL after 10 weeks of administration. The serum thrombopoietin (TPO) level
      was markedly elevated, and anti-TPO receptor (TPOR) antibody was detected in the
      patient's serum. Anti-TPOR antibody may play an important role in some cases of
      prolonged thrombocytopenia after allogeneic hematopoietic stem cell
      transplantation with unknown etiology, and eltrombopag could be a novel
      therapeutic option for such cases.

PMID- 25964102
TI  - Medical students' personal experience of high-stakes failure: case studies using
      interpretative phenomenological analysis.
AB  - BACKGROUND: Failing a high-stakes assessment at medical school is a major event
      for those who go through the experience. Students who fail at medical school may
      be more likely to struggle in professional practice, therefore helping
      individuals overcome problems and respond appropriately is important. There is
      little understanding about what factors influence how individuals experience
      failure or make sense of the failing experience in remediation. The aim of this
      study was to investigate the complexity surrounding the failure experience from
      the student's perspective using interpretative phenomenological analysis (IPA).
      METHODS: The accounts of three medical students who had failed final re-sit
      exams, were subjected to in-depth analysis using IPA methodology. IPA was used to
      analyse each transcript case-by-case allowing the researcher to make sense of the
      participant's subjective world. The analysis process allowed the complexity
      surrounding the failure to be highlighted, alongside a narrative describing how
      students made sense of the experience. RESULTS: The circumstances surrounding
      students as they approached assessment and experienced failure at finals were a
      complex interaction between academic problems, personal problems (specifically
      finance and relationships), strained relationships with friends, family or
      faculty, and various mental health problems. Each student experienced multi
      dimensional issues, each with their own individual combination of problems, but
      experienced remediation as a one-dimensional intervention with focus only on
      improving performance in written exams. What these students needed to be included
      was help with clinical skills, plus social and emotional support. Fear of
      termination of the their course was a barrier to open communication with staff.
      CONCLUSIONS: These students' experience of failure was complex. The experience of
      remediation is influenced by the way in which students make sense of failing.
      Generic remediation programmes may fail to meet the needs of students for whom
      personal, social and mental health issues are a part of the picture.

PMID- 25964101
TI  - Pharmacologically Increasing Mdm2 Inhibits DNA Repair and Cooperates with
      Genotoxic Agents to Kill p53-Inactivated Ovarian Cancer Cells.
AB  - The Mdm2 oncogene is a negative regulator of the p53 tumor suppressor and
      recently identified inhibitor of DNA break repair. Nutlin-3 is a small-molecule
      inhibitor of Mdm2-p53 interaction that can induce apoptosis in cancer cells
      through activation of p53. Although this is a promising therapy for those cancers
      with wild-type p53, half of all human cancers have inactivated p53. Here, we
      reveal that a previously unappreciated effect of Nutlin is inhibition of DNA
      break repair, stemming from its ability to increase Mdm2 protein levels. The
      Nutlin-induced increase in Mdm2 inhibited DNA double-strand break repair and
      prolonged DNA damage response signaling independent of p53. Mechanistically, this
      effect of Nutlin required Mdm2 and acted through Nbs1 of the Mre11-Rad50-Nbs1 DNA
      repair complex. In ovarian cancer cells, where >90% have inactivated p53, Nutlin
      combined with the genotoxic agents, cisplatin or etoposide, had a cooperative
      lethal effect resulting in increased DNA damage and apoptosis. Therefore, these
      data demonstrate an unexpected consequence of pharmacologically increasing Mdm2
      levels that when used in combination with genotoxic agents induces synthetic
      lethality in ovarian cancer cells, and likely other malignant cell types, that
      have inactivated p53. IMPLICATIONS: Data reveal a therapeutically beneficial
      effect of pharmacologically increasing Mdm2 levels combined with chemotherapeutic
      agents for malignancies that have lost functional p53.

PMID- 25964103
TI  - Fasted-state simulated intestinal fluid "FaSSIF-C", a cholesterol containing
      intestinal model medium for in vitro drug delivery development.
AB  - A set of biorelevant media "fasted-state simulated intestinal fluid with
      cholesterol (FaSSIF-C)" for the in vitro study of intestinal drug dissolution in
      the duodenum was developed. These contain cholesterol at the same levels as in
      human bile: the cholesterol content of FaSSIF-7C is equivalent to healthy female,
      FaSSIF-10C to healthy male persons, and FaSSIF-13C to several disease cases that
      lead to gallstones. The fluids were studied in three aspects: biocompatibility,
      intestinal nanostructure, and solubilizing power of hydrophobic drugs of the BCS
      class II. The biocompatibility study showed no toxic effects in a Caco-2 cell
      system. The drug-solubilizing capacity toward Fenofibrate, Danazol, Griseofulvin,
      and Carbamazepine was assessed as example. It varied with the cholesterol content
      widely from a fourfold improvement to a twofold reduction. The nanostructure
      study by dynamic light scattering and small-angle neutron scattering indicated
      vesicles as the main component of FaSSIF-C in equilibrium (>1 h), but at high
      cholesterol content, larger particles were observed as a minor contribution. The
      neutron experiments indicated the presence of complex micelle-vesicle mixtures,
      even after 1 h development of fed-state bile model to FaSSIF. The results
      indicate that cholesterol affects some drugs in solubilization and particle size
      in intestinal model fluids.

PMID- 25964104
TI  - Metal complexes of curcumin--synthetic strategies, structures and medicinal
      applications.
AB  - This Tutorial Review presents an overview on the synthesis, characterization and
      applications of metal complexes containing curcumin (=1,7-bis(4-hydroxy-3
      methoxyphenyl)-1,6-heptadiene-3,5-dione) and its derivatives as ligands.
      Innovative synthetic strategies leading to soluble and crystallizable metal
      curcumin complexes are outlined in detail. Special emphasis is placed on the
      highly promising and exciting medicinal applications of metal curcumin complexes,
      with the three most important areas being anticancer activity and selective
      cytotoxicity, anti-Alzheimer's disease activity, and
      antioxidative/neuroprotective effects. Overall, this Tutorial Review provides the
      first general overview of this emerging and rapidly expanding field of
      interdisciplinary research. 

PMID- 25964105
TI  - A Factor Analytic Approach to the Validation of the Word Memory Test and Test of
      Memory Malingering as Measures of Effort and Not Memory.
AB  - Research has demonstrated the utility of performance validity tests (PVTs) as a
      method of determining adequate effort during a neuropsychological evaluation.
      Although some studies affirm that forced-choice PVTs measure effort rather than
      memory, doubts remain in the literature. The purpose of the current study was to
      evaluate the relationship between effort and memory variables in a mild traumatic
      brain injury (TBI) sample (n = 160) by separating memory and effort as distinct
      factors while statistically controlling for the shared covariance between the
      variables. A two-factor solution was extracted such that the five PVT variables
      loaded on Factor 1 and the four memory variables loaded on Factor 2. The pattern
      matrix, which controls for the covariance between variables, provided clear
      support of two highly distinct factors with minimal cross-loadings. Our findings
      support assertions that PVTs measure effort independent of memory in veterans
      with mild TBI. 

PMID- 25964106
TI  - Laparoscopic sleeve gastrectomy in Asia: Long term outcome and revisional
      surgery.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a popular stand-alone
      bariatric surgery, despite a paucity of long-term data. Hence, this study is to
      report the long-term outcome of LSG as primary bariatric procedure and the result
      of revisional surgery. METHODS: With retrospective analysis of a prospective
      bariatric database, participants who defaulted clinic follow-up were interviewed
      by telephone. A total of 667 LSG was performed as primary bariatric procedure
      (2006-2012) with mean age of 34.5 +/- 9.7 years old, female 74.7%, mean body mass
      index (BMI) 37.3 +/- 8.1 kg/m(2). A 36-F bougie was used for all cases. RESULTS:
      There were 61 patients available with long-term data. The weight loss outcome at
      1 year, 2 years, 3 years, 4 years, and 5 years showed a mean BMI 26.3, 25.2,
      25.3, 27.1, and 26.2 with mean excess weight loss (EWL) 76.0%, 79.6%, 77.3%,
      73.4%, and 72.6% respectively. However, 17% patients developed de novo gastro
      esophageal reflux disease (GERD). Eighteen patients (2.2%) needed surgical
      revisions due to weight regain (n = 6), persistent type 2 diabetes mellitus
      (T2DM; n = 2), stricture (n = 2), and GERD (n = 8). The revision resulted in an
      additional mean excess weight loss of 23.8% with mean BMI 24.9 kg/m(2) at 6
      months postoperatively. There was a 23.7% mean reduction of HbA1c with one
      patient who was in complete diabetic remission at 1 year. CONCLUSION: Our results
      showed LSG is a durable bariatric procedure with > 70% EWL at 5 years despite a
      high incidence of GERD. The need for revision of LSG is low and mainly for GERD.

PMID- 25964107
TI  - Diffuse pulmonary meningotheliomatosis: A diagnostically challenging entity on
      fine-needle aspiration cytology.
AB  - Diffuse pulmonary meningotheliomatosis (DPM) is an exceedingly rare entity
      consisting of multiple minute pulmonary meningothelial-like nodules profusely
      involving the lungs. To the best of our knowledge, we present the first cytologic
      description of this uncommon lesion from a 57-year-old nonsmoking woman.
      Computerized tomographic-guided fine-needle aspiration cytology from a left upper
      lobe nodule showed whorled/nested clusters of elongated cells with oval nuclei,
      clear pseudonuclear inclusions, nuclear grooves/indentations, smooth nuclear
      contours, fine granular chromatin, inconspicuous nucleoli, and abundant
      fibrillary cytoplasm with indistinct cell borders. The subsequent pulmonary wedge
      resections confirmed the diagnosis of DPM. As this condition is exceptionally
      rare, familiarity with these cytologic features is of the essence to accurately
      establish this challenging diagnosis.

PMID- 25964108
TI  - Sequential percutaneous closure of mitral prosthetic paravalvular leak and
      complex communicating pseudoaneurysms of the ascending aorta and subvalvar left
      ventricular outflow tract.
AB  - Ascending aortic and subvalvar left ventricular outflow tract (LVOT)
      pseudoaneurysms are rare complications following aortic valve or root replacement
      surgery. Clinically important paravalvular leaks are rare complications following
      any valve replacement surgery. We report an unusual case of sequential
      percutaneous closure of mitral prosthetic paravalvular leak and complex
      communicating ascending aortic and subvalvar LVOT pseudoaneurysms, which
      demonstrates the importance of multimodal imaging assessment surrounding
      percutaneous closure. (c) 2015 Wiley Periodicals, Inc. 

PMID- 25964109
TI  - Role of Lipocalin-type prostaglandin D2 synthase (L-PGDS) and its metabolite,
      prostaglandin D2, in preterm birth.
AB  - The objective of the study was to investigate the role of prostaglandin D2 during
      pregnancy and its mediator Lipocalin-type prostaglandin D2 synthase (L-PGDS) as a
      predictor of preterm birth (PTB). Transgenic L-PGDS (+/+), L-PGDS (-/-) and
      C57BL/6 control pregnant mice models were used to determine the effect of DP1 and
      DP2 receptor antagonists in lipopolysaccharide (LPS)-induced PTB mice. In
      addition, L-PGDS levels were measured in the cervicovaginal secretions (CVS) of
      370 pregnant women using ELISA and further processed for isoform detection using
      2-D gel electrophoresis. Our results found that C57BL/6 control mice (n = 26),
      transgenic L-PGDS (+/+) (n = 26), demonstrated an 89% and 100% preterm birth in
      LPS (intraperitoneal injection, 20mg/kg) induced mice model respectively.
      Interestingly, the incidence of PTB was significantly reduced to 40% in L-PGDS (
      /-) knockout mice (n = 26). DP1 and DP2 receptor antagonists (0.264 MUg/day, dose
      of 0.1 MUg/MUl with the flow of 0.11 MUl/h for 28 day using Alzet pumps) were
      used to investigate the effect in LPS-induced PTB in C57BL/6 mice and found 3.3
      fold increase in viable pups after LPS-induction. In addition, L-PGDS levels were
      measured in CVS samples and found that PTB women (n = 296) had two-fold higher
      levels compared to full term births (n = 74) and established a significant
      inverse correlation between levels of L-PGDS and days to expected delivery by
      using 370 preterm birth CVS samples. Elevated L-PGDS levels in the CVS of women
      may be considered as a potential biomarker for PTB in future. Secondly, the use
      of DP1 and DP2 receptor antagonists may represent novel tocolytic agents for the
      treatment of PTB.

PMID- 25964110
TI  - An "ancient" complexity? Evolutionary morphology of the circulatory system in
      Xiphosura.
AB  - Horseshoe crabs (Xiphosura) have been an object of zoological research for almost
      200 years. Although some morphological work on the circulatory system has been
      done, the three-dimensional structure of this complex organ system has never been
      shown satisfactorily and some crucial questions remain unanswered. Here, the
      circulatory systems of juveniles of the horseshoe crab taxa Limulus polyphemus
      and Carcinoscorpius rotundicauda were investigated using a combination of an
      injection method and micro-computed tomography. Data were processed and 3D
      visualized using reconstruction software. Furthermore, the heart was examined
      using scanning electron microscopy. Additionally, the histology of some
      structures was investigated via light microscopy and transmission electron
      microscopy. The results show the high degree of complexity of the arterial and
      lacunar systems of Xiphosura and provide insights into their three-dimensional
      structure and relationship to other organ systems such as the central nervous
      system. We show that the major lacunae, previously described as vessel-like -
      though indeed highly ramified - can clearly be distinguished from arteries in
      histological sections because they have no distinct walls. Similarities and
      differences between the xiphosuran species and arachnids are highlighted and
      possible phylogenetic implications and evolutionary scenarios discussed. 

PMID- 25964111
TI  - Chemoenzymatic Synthesis of a Type 2 Blood Group A Tetrasaccharide and
      Development of High-throughput Assays Enables a Platform for Screening Blood
      Group Antigen-cleaving Enzymes.
AB  - A facile enzymatic synthesis of the methylumbelliferyl beta-glycoside of the type
      2 A blood group tetrasaccharide in good yields is reported. Using this compound,
      we developed highly sensitive fluorescence-based high-throughput assays for both
      endo-beta-galactosidase and alpha-N-acetylgalactosaminidase activity specific for
      the oligosaccharide structure of the blood group A antigen. We further
      demonstrate the potential to use this assay to screen the expressed gene products
      of metagenomic libraries in the search for efficient blood group antigen-cleaving
      enzymes. 

PMID- 25964112
TI  - Mapping strategy for multiple atrial tachyarrhythmias in a transplant heart.
AB  - BACKGROUND: Different atrial arrhythmias can coexist in the recipient and donor
      atria after heart transplantation. CASE PRESENTATION: We report an unusual case
      of a patient with three different types of atrial arrhythmia after heart
      transplantation: an atrial fibrillation in the recipient atria, and a
      cavotricuspid isthmus dependent atrial flutter and a focal atrial tachycardia in
      the donor atria. 3D electroanatomical mapping and ablation were guided by remote
      magnetic navigation (RMN). Atrial fibrillation continued in the recipient atria
      even after the donor heart was converted to sinus rhythm by ablation.
      CONCLUSIONS: It is critical to understand the surgical anatomy of a bi-atrial
      anastomosis and its relevant electrical activation pattern before ablation.
      Appropriate electroanatomical mapping strategy with RMN can facilitate the
      successful ablation of post-transplant atrial arrhythmias.

PMID- 25964113
TI  - Prospective functional outcomes in sequential population based cohorts of stage
      III/ IV oropharyngeal carcinoma patients treated with 3D conformal vs. intensity
      modulated radiotherapy.
AB  - BACKGROUND AND PURPOSE: To compare early (3 and 6 month) and later (12 and 24
      month) functional outcomes of stage III and IV (M0) oropharyngeal squamous cancer
      patients treated in sequential cohorts with 3D conformal (3DCRT) or intensity
      modulated radiotherapy (IMRT). PATIENTS AND METHODS: 200 patients in sequential
      population based cohorts of 83 and 117 patients treated at a single institution
      with 3DCRT and then IMRT respectively were prospectively assessed at pre
      treatment and 3, 6, 12 and 24 months post treatment. A standard functional
      outcomes protocol including performance status (KPS, ECOG), 3 Performance Status
      scales for Head and Neck (PSS-HN), the Royal Brisbane Hospital Outcome Measure
      for Swallowing (RBHOMS), Voice Handicap Index-10 (VHI-10) and self-rated
      xerostomia were applied. RESULTS: Mean age at diagnosis was 59 years. The primary
      site was base of tongue in 77 and tonsil or soft palate in 123 patients. Median
      follow up was 2.5 years for the second cohort. Concomitant therapy was used in
      159 (79.5%). Overall survival at 3 years was 75.6% and 71.5% for IMRT and 3DCRT
      cohorts respectively (not significant). A multiple imputation technique was used
      to estimate missing values in order to avoid a healthy patient bias. KPS and ECOG
      reached nadirs at 3 to 6 months but approached baseline values at 12 to 24 months
      and did not differ by treatment. The 3 PSS-HN scales, Eating in Public (p <
      0.001), Understandability of Speech (p = 0.009) and Oral Diet Texture (p = 0.002)
      and all showed significantly better outcomes in favor of IMRT. The RBHOMS showed
      a difference in favor of IMRT which appeared during 3 to 6 months (p < 0.001).
      The VHI-10 also showed a difference in favor of IMRT (p = 0.015). Self-rated
      xerostomia did not differ at 3 and 6 months but was significantly better in favor
      of IMRT after 12 months p = 0.005 CONCLUSIONS: A prospectively administered
      functional outcomes protocol showed meaningful differences in favor of IMRT over
      3DCRT early (3-6 months) and later (12-24 months) in the treatment of
      oropharyngeal carcinoma with equivalent survival. These data support the adoption
      of IMRT as the standard radiation treatment method for patients with stage III
      and IV (M0) oropharyngeal squamous carcinoma. KPS and ECOG may not be sensitive
      to oropharyngeal cancer patients' functional outcomes by treatment.

PMID- 25964114
TI  - Preoperative serum CA125: a useful marker for surgical management of endometrial
      cancer.
AB  - BACKGROUND: Surgery plays an important role in the management of endometrial
      cancer at all stages, particularly early clinical stage. There are still many
      unanswered questions regarding optimal surgical management of endometrial cancer,
      particularly regarding which patients should undergo lymphadenectomy. The aim of
      this study was to evaluate the role of preoperative cancer antigen 125 (CA125)
      serum levels for surgical management in endometrial cancer patients. METHODS: A
      total of 995 patients with endometrial cancer, according to inclusion criteria of
      a preoperative serum level of CA125, were selected. The association between
      clinicopathological factors and CA125 were analyzed. Receiver operating
      characteristic (ROC) curve was used to evaluate the role of preoperative serum
      CA125 in predicting lymph node metastasis, adnexal involement, cervical stromal
      invasion in all patients, especially patients with clinical stage I. Survival
      analyses were also performed according to the four groups of preoperative CA125
      serum levels. RESULTS: Elevated CA125 level was significantly associated with all
      clinicopathological parameters, including age and menopause, but not histology
      type. ROC curve analysis results showed the CA125 serum level of 25 U/mL was the
      best cutoff to predict the lymph node metastasis. It was with 78% of sensitivity,
      78% of specificity, 77.6% of false positive rate, 2.3% of false negative rate in
      all patients. In patients with clinical stage I, it was with 71.7% of
      sensitivity, 77.6% of specificity, 83.3% of false positive rate, 2.2% of false
      negative rate. The best cutoff to evaluate adnexal involement in patients with
      clinical stage I was 30U/ml, with 81% sensitivity, and 78.4% specificity.
      Survival analysis revealed CA125, FIGO stage, histology grade, and positive
      peritoneal cytology as independent prognostic factors of endometrial cancer.
      CONCLUSION: Preoperative serum CA125 is an important predictor for patients with
      endometrial cancer and it should be taken into consideration when surgical
      management is determined, especially if a lymphadenectomy should be undertaken in
      patients with clinical stage I.

PMID- 25964115
TI  - Association of elevated apoA-I glycation and reduced HDL-associated paraoxonase1,
      3 activity, and their interaction with angiographic severity of coronary artery
      disease in patients with type 2 diabetes mellitus.
AB  - OBJECTIVE: To investigate whether apolipoprotein A (apoA)-I glycation and
      paraoxonase (PON) activities are associated with the severity of coronary artery
      disease (CAD) in patients with type 2 diabetes mellitus (T2DM). METHODS: Relative
      intensity of apoA-I glycation and activities of high-density lipoprotein (HDL)
      associated PON1 and PON3 were determined in 205 consecutive T2DM patients with
      stable angina with (n = 144) or without (n = 61) significant CAD (luminal
      diameter stenosis >= 70 %). The severity of CAD was expressed by number of
      diseased coronary arteries, extent index, and cumulative coronary stenosis score
      (CCSS). RESULTS: The relative intensity of apoA-I glycation was higher but the
      activities of HDL-associated PON1 and PON3 were lower in diabetic patients with
      significant CAD than in those without. The relative intensity of apoA-I glycation
      increased but the activities of HDL-associated PON1 and PON3 decreased stepwise
      from 1 - to 3 - vessel disease patients (P for trend < 0.001). After adjusting
      for possible confounding variables, the relative intensity of apoA-I glycation
      correlated positively, while the activities of HDL-associated PON1 and PON3
      negatively, with extent index and CCSS, respectively. At high level of apoA-I
      glycation (8.70 ~ 12.50 %), low tertile of HDL-associated PON1 (7.03 ~ 38.97U/mL)
      and PON3 activities (7.11 ~ 22.30U/mL) was associated with a 1.97- and 2.49- fold
      increase of extent index and 1.73- and 2.68- fold increase of CCSS compared with
      high tertile of HDL-associated PON1 (57.85 ~ 154.82U/mL) and PON3 activities
      (39.63 ~ 124.10U/mL), respectively (all P < 0.01). CONCLUSIONS: Elevated apoA-I
      glycation and decreased activities of HDL-associated PON1 and PON3, and their
      interaction are associated with the presence and severity of CAD in patients with
      T2DM.

PMID- 25964116
TI  - Laparoscopic CBD exploration using a V-shaped choledochotomy.
AB  - BACKGROUND: Laparoscopic common bile duct exploration (LCBDE) is a treatment
      modality for choledocholithiasis. The advantages of this technique are that it is
      less invasive than conventional open surgery and it permits single-stage
      management; however, other technical difficulties limit its use. The aim of this
      article is to introduce our novel technique for LCBDE, which may overcome some of
      the limitations of conventional LCBDE. Since December 2013, ten patients have
      undergone LCBDE using a V-shaped choledochotomy (V-CBD). After the confluence of
      the cystic duct and the CBD were exposed, a V-shaped incision was made along the
      medial wall of the cystic duct and the lateral wall of the common hepatic duct,
      which comprise two sides of Calot's triangle. The choledochoscope was inserted
      into the lumen of the CBD through a V-shaped incision, and all CBD stones were
      retrieved using a basket or a Fogarty balloon catheter or were irrigated with
      saline. After CBD clearance was confirmed using the choledochoscope, the
      choledochotomy was closed with the bard absorbable suture material known as V
      loc. RESULTS: The diameter of the CBD ranged from 8 to 30 mm, and the mean size
      of the stones was 11.6 +/- 8.4 mm. The mean operative time was 97.8 +/- 30.3 min,
      and the mean length of the postoperative hospital stay was 6.0 +/- 4.6 days. All
      patients recovered without any postoperative complications, except for one
      patient who developed postoperative pancreatitis. No conversions to laparotomy
      were observed, and there were no recurrent stones and no need of T-tube
      insertion. CONCLUSIONS: This report suggests that our novel technique, known as V
      CBD, may represent a feasible and straightforward procedure for treating
      choledocholithiasis, especially when the CBD is not dilated.

PMID- 25964117
TI  - Serum Bile Acids Are Associated with Pathological Progression of Hepatitis B
      Induced Cirrhosis.
AB  - Recent metabonomic studies have identified an important role of bile acids in
      patients with liver cirrhosis. Serum bile acids, such as glycocholate (GCA),
      glycochenodeoxycholate (GCDCA), taurocholate (TCA), and taurochenodeoxycholate
      (TCDCA), increased significantly in liver cirrhosis patients. Our recently
      published urinary metabonomic study showed that glycocholate 3-glucuronide,
      taurohyocholate, TCA, glycolithocholate 3-sulfate, and glycoursodeoxycholate
      (GUDCA) were markedly increased in hepatitis B-induced cirrhotic patients (n =
      63) compared with healthy controls (n = 31). The urinary levels of GUDCA were
      able to differentiate among three stages of cirrhotic patients with Child-Pugh
      (CP) score A, B, and C. In this study, we recruited two new cohorts of patients
      with hepatitis-B-induced cirrhosis and healthy control subjects and
      quantitatively profiled their serum bile acids using ultra-performance liquid
      chromatography triple quadrupole mass spectrometry. Serum bile acid profile and
      corresponding differential bile acids were characterized, in addition to the
      blood routine, liver, and renal function tests. The alterations of bile acids
      contributing to the intergroup variation between healthy controls and cirrhotic
      patients and among pathological stages of CP grade A, B and C were also
      investigated. Five bile acids, GCA, GCDCA, TCA, TCDCA, and GUDCA, were
      significantly altered among different stages of liver cirrhosis (n = 85), which
      was validated with an independent cohort of cirrhotic patients (n = 53). Our
      results show that dynamic alteration of serum bile acids is indicative of an
      exacerbated liver function, highlighting their potential as biomarkers for
      staging the liver cirrhosis and monitoring its progression. 

PMID- 25964118
TI  - Human endometrial mesenchymal stem cells restore ovarian function through
      improving the renewal of germline stem cells in a mouse model of premature
      ovarian failure.
AB  - BACKGROUND: Human endometrial mesenchymal stem cells (EnSCs) derived from
      menstrual blood have mesenchymal stem/stromal cells (MSCs) characteristics and
      can differentiate into cell types that arise from all three germ layers. We
      hypothesized that EnSCs may offer promise for restoration of ovarian dysfunction
      associated with premature ovarian failure/insufficiency (POF/POI). METHODS: Mouse
      ovaries were injured with busulfan and cyclophosphamide (B/C) to create a damaged
      ovary mouse model. Transplanted EnSCs were injected into the tail vein of
      sterilized mice (Chemoablated with EnSCs group; n = 80), or culture medium was
      injected into the sterilized mice via the tail vein as chemoablated group (n =
      80). Non-sterilized mice were untreated controls (n = 80). Overall ovarian
      function was measured using vaginal smears, live imaging, mating trials and
      immunohistochemical techniques. RESULTS: EnSCs transplantation increased body
      weight and improved estrous cyclicity as well as restored fertility in sterilized
      mice. Migration and localization of GFP-labeled EnSCs as measured by live imaging
      and immunofluorescent methods indicated that GFP-labeled cells were undetectable
      48 h after cell transplantation, but were later detected in and localized to the
      ovarian stroma. 5'-bromodeoxyuridine (BrdU) and mouse vasa homologue (MVH)
      protein double-positive cells were immunohistochemically detected in mouse
      ovaries, and EnSC transplantation reduced depletion of the germline stem cell
      (GSCs) pool induced by chemotherapy. CONCLUSION: EnSCs derived from menstrual
      blood, as autologous stem cells, may restore damaged ovarian function and offer a
      suitable clinical strategy for regenerative medicine.

PMID- 25964119
TI  - Provider-agency fit in substance abuse treatment organizations: implications for
      learning climate, morale, and evidence-based practice implementation.
AB  - BACKGROUND: Substance abuse agencies have been slow to adopt and implement
      evidence-based practices (EBPs), due in part to poor provider morale and
      organizational climates that are not conducive to successful learning and
      integration of these practices. Person-organization fit theory suggests that
      alignment, or fit, between provider- and agency-level characteristics regarding
      the implementation of EBPs may influence provider morale and organizational
      learning climate and, thus, implementation success. The current study
      hypothesized that discrepancies, or lack of fit, between provider- and agency
      level contextual factors would negatively predict provider morale and
      organizational learning climate, outcomes shown to be associated with successful
      EBP implementation. METHODS: Direct service providers (n = 120) from four
      substance abuse treatment agencies responded to a survey involving provider
      morale, organizational learning climate, agency expectations for EBP use, agency
      resources for EBP use, and provider attitudes towards EBP use. Difference scores
      between combinations of provider- and agency-level factors were computed to model
      provider-agency fit. Quadratic regression analyses were conducted to more
      adequately and comprehensively model the level of the dependent variables across
      the entire "fit continuum". RESULTS: Discrepancies, or misfit, between agency
      expectations and provider attitudes and between agency resources and provider
      attitudes were associated with poorer provider morale and weaker organizational
      learning climate. For all hypotheses, the curvilinear model of provider-agency
      discrepancies significantly predicted provider morale and organizational learning
      climate, indicating that both directions of misfit (provider factors more
      favorable than agency factors, and vice-versa) were detrimental to morale and
      climate. However, outcomes were most negative when providers viewed EBPs
      favorably, but perceived that agency expectations and resources were less
      supportive of EBP use. CONCLUSIONS: The current research benefits from a strong
      theoretical framework, consistent findings, and significant practical
      implications for substance abuse treatment agencies. Comprehensive attempts to
      strengthen outcomes related to EBP implementation must consider both provider-
      and agency-level characteristics regarding EBP use. Organizational efforts to
      more closely align provider attitudes and agency priorities will likely
      constitute a key strategy in fostering the implementation of EBPs in substance
      abuse treatment organizations.

PMID- 25964120
TI  - Actual implementation of sick children's rights in Italian pediatric units: a
      descriptive study based on nurses' perceptions.
AB  - BACKGROUND: Several charters of rights have been issued in Europe to solemnly
      proclaim the rights of children during their hospital stay. However,
      notwithstanding such general declarations, the actual implementation of
      hospitalized children's rights is unclear. The purpose of this study was to
      understand to which extent such rights, as established by the two main existing
      charters of rights, are actually implemented and respected in Italian pediatric
      hospitals and the pediatric units of Italian general hospitals, as perceived by
      the nurses working in them. METHODS: Cross-sectional study. A 12-item online
      questionnaire was set up and an invitation was sent by email to Italian pediatric
      nurses using professional mailing lists and social networks. Responders were
      asked to score to what extent each right is respected in their hospital using a
      numeric scale from 1 (never) to 5 (always). RESULTS: 536 questionnaires were
      returned. The best implemented right is the right of children to have their
      mothers with them (mean score 4.47). The least respected one is the right of
      children to express their opinion about care (mean 3.01). Other rights considered
      were the right to play (4.29), the right to be informed (3.95), the right to the
      respect of privacy (3.75), the right to be hospitalized with peers (3.39), the
      right not to experience pain ever (3.41), and the right to school (3.07).
      According to the majority of nurses, the most important is the right to pain
      relief. Significant differences in the implementation of rights were found
      between areas of Italy and between pediatric hospitals and pediatric units of
      general hospitals. CONCLUSION: According to the perception of pediatric nurses,
      the implementation of the rights of hospitalized children in Italian pediatrics
      units is still limited.

PMID- 25964122
TI  - Preparation of melamine molecularly imprinted polymer by computer-aided design.
AB  - Melamine was chosen as template, methacrylic acid was chosen as functional
      monomer, and divinylbenzene, ethylene glycol dimethacrylate, trimethylolpropane
      trimethylacrylate were chosen as cross-linking agents, respectively. The WB97XD/6
      31G(d, p) method was used to calculate the geometry optimization of the different
      imprinting ratios, the action sites, the bonding situation, and the optimization
      of the cross-linking agents. The nature of the imprinting effect was also studied
      by the atoms in molecules theory. The theoretical results showed that melamine
      interacts with methacrylic acid by hydrogen bonding, and the melamine molecularly
      imprinted polymers with a molar ratio of 1:6 have the most hydrogen bonds and the
      most stable structure. Divinylbenzene is the best cross-linking agent for the
      melamine molecularly imprinted polymers. The melamine molecularly imprinted
      polymers were synthesized by precipitation polymerization. The results showed
      that the maximum adsorption capacity for molecularly imprinted polymers towards
      melamine is 19.84 mg/g, and the adsorption quantity of the polymers to melamine
      is obviously higher than that of cyromazine, cyanuric acid, and trithiocyanuric
      in milk. This study could provide theoretical and experimental references for the
      screening of the imprinting ratio and the cross-linking agent for the given
      template and monomer system. 

PMID- 25964121
TI  - Structural analyses of the chromatin remodelling enzymes INO80-C and SWR-C.
AB  - INO80-C and SWR-C are conserved members of a subfamily of ATP-dependent chromatin
      remodelling enzymes that function in transcription and genome-maintenance
      pathways. A crucial role for these enzymes is to control chromosomal distribution
      of the H2A.Z histone variant. Here we use electron microscopy (EM) and two
      dimensional class averaging to demonstrate that these remodelling enzymes have
      similar overall architectures. Each enzyme is characterized by a dynamic 'tail'
      domain and a compact 'head' that contains Rvb1/Rvb2 subunits organized as
      hexameric rings. EM class averages and mass spectrometry support the existence of
      single heterohexameric rings in both SWR-C and INO80-C. EM studies define the
      position of the Arp8/Arp4/Act1 module within INO80-C, and we find that this
      module enhances nucleosome-binding affinity but is largely dispensable for
      remodelling activities. In contrast, the Ies6/Arp5 module is essential for INO80
      C remodelling, and furthermore this module controls conformational changes that
      may couple nucleosome binding to remodelling. 

PMID- 25964123
TI  - Accuracy of ultrasound in antenatal diagnosis of placental attachment disorders.
AB  - OBJECTIVES: To evaluate the accuracy of ultrasound in the diagnosis of placenta
      accreta and its variants, and to assess the impact of prenatal diagnosis in our
      population. METHODS: A total of 314 women with placenta previa were enrolled
      prospectively and underwent transabdominal and transvaginal ultrasound
      examinations. An ultrasound diagnosis (grayscale and color/power Doppler) of
      placental attachment disorder (PAD) was based on the detection of at least two of
      the following ('two-criteria system'): loss/irregularity of the retroplacental
      clear zone, thinning/interruption of the uterine serosa-bladder wall interface,
      turbulent placental lacunae with high velocity flow, myometrial thickness < 1 mm,
      increased vascularity of the uterine serosa-bladder wall interface, loss of
      vascular arch parallel to the basal plate and/or irregular intraplacental
      vascularization. Definitive diagnosis was made at delivery by Cesarean section.
      Maternal outcome in cases diagnosed antenatally was compared with that in cases
      diagnosed at delivery. RESULTS: There were 37/314 cases of PAD (29 anterior and
      eight posterior). The two-criteria system identified 30 cases of placenta
      accreta, providing a sensitivity of 81.1% and specificity of 98.9%. When anterior
      and posterior placentae were considered separately, the detection rates of PAD
      were 89.7 and 50.0%, respectIvely. Maternal outcome was better in women with
      prenatal diagnosis of PAD, as seen by less blood loss and shorter
      hospitalization. CONCLUSIONS: Our data confirmed that grayscale and color Doppler
      ultrasound have good performance in the diagnosis of PAD and that prenatal
      diagnosis improves maternal outcome. Copyright (c) 2015 ISUOG. Published by John
      Wiley & Sons Ltd.

PMID- 25964124
TI  - Growing gaps: The importance of income and family for educational inequalities in
      mortality among Swedish men and women 1990-2009.
AB  - AIMS: Although absolute levels of mortality have decreased among Swedish men and
      women in recent decades, educational inequalities in mortality have increased,
      especially among women. The aim of this study is to disentangle the role of
      income and family type in educational inequalities in mortality in Sweden during
      1990-2009, focusing on gender differences. METHODS: Data on individuals born in
      Sweden between the ages of 30 and 74 years were collected from total population
      registries, covering a total of 529,275 deaths and 729 million person-months.
      Temporary life expectancies (age 30-74 years) by education were calculated using
      life tables, and rate ratios were estimated with Poisson regression with robust
      standard errors. RESULTS: Temporary life expectancy improved among all groups
      except low educated women. Relative educational inequalities in mortality (RRs)
      increased from 1.79 to 1.98 among men and from 1.78 to 2.10 among women.
      Variation in family type explained some of the inequalities among men, but not
      among women, and did not contribute to the trend. Variation in income explained a
      larger part of the educational inequalities among men compared to women and also
      explained the increase in educational inequalities in mortality among men and
      women. CONCLUSIONS: Increasing educational inequalities in mortality in Sweden
      may be attributed to the increase in income inequalities in mortality.

PMID- 25964125
TI  - Suicidal risk and sexual orientation in adolescence: a population-based study in
      Iceland.
AB  - AIM: Suicidality is an important public health problem, particularly among
      lesbian, gay, and bisexual (LGB) adolescents and young adults. The purpose of the
      present study is to compare the rate of suicide ideations and attempts among LGB
      adolescent to that of non-LGB adolescents in a population-based sample, and to
      identify important protective factors as well as risk factors Method: We used the
      Icelandic data set from the 2009/2010 Health Behaviour in School-aged Children
      (HBSC) study. The sample consisted of 3813 grade 10 Icelandic adolescents; 1876
      girls and 1937 boys. The participants were asked about attraction and/or
      activity, as well as about suicidal ideation and/or attempts. The questionnaire
      also included various other items regarding health and lifestyle. RESULTS: LGB
      adolescents were five to six times more likely to have had frequent suicidal
      ideations. Factors that were associated with less suicide ideations and fewer
      attempts were easy communication and liking school. The LGB girls were six times
      more likely to have had frequent suicide attempts, whilst the LGB boys were 17
      times more likely to have attempted suicide that often. No specific protective or
      risk factors were identified for suicidality in LGB adolescents other than
      bullying. CONCLUSIONS: Adolescents that had engaged in heterosexual activity and
      those that had LGB attraction had similarly heightened risk for suicidality, but
      sexually active LGB adolescents were far more likely to have suicidal ideations
      or to have attempted suicide.

PMID- 25964126
TI  - Comparison of mental distress in patients with low back pain and a population
      based control group measured by Symptoms Check List--A case-referent study.
AB  - PURPOSE: Mental distress is common in persons experiencing low back pain and who
      are sick-listed or at risk of being sick-listed. It is, however, not known how
      mental distress measured by the Symptoms Check List-90 differs between patients
      with low back pain and the general population. The objective of this study was to
      compare mental symptoms and distress as measured by the Symptoms Check List-90 in
      sick-listed or at risk of being sick-listed patients with low back pain with a
      population-based control group. METHODS: Mental distress was compared in a group
      of patients with low back pain (n=770) and a randomly selected population-based
      reference group (n=909). Established Danish cut-off values for mental distress
      were used to evaluate the mental distress status in the low back pain and control
      group and logistic regression was used to calculate odds ratios for the Global
      Severity Index and the symptom scales of the Symptoms Check List-90 while
      controlling for baseline demographic differences between the groups. RESULTS:
      Group mean scores showed that all symptom scales and the Global Severity Index
      for both sexes were statistically elevated in the low back pain group, except for
      interpersonal sensitivity in women. When the scores were dichotomized to cases
      and non-cases of mental distress, a significantly higher prevalence of cases was
      observed in the low back pain group compared to the reference group on all
      symptom check list scales, except for paranoid ideation for both sexes and
      interpersonal sensitivity for women. The biggest between-group difference was
      observed for the somatization symptom scale. CONCLUSIONS: Low back pain patients
      who are sick-listed or at risk of being sick-listed, are more mentally distressed
      compared to a randomly selected sample of the general Danish population. Self
      reported symptoms of somatization, anxiety, phobic anxiety, obsessive-compulsive,
      depression and hostility are all more common among patients with low back pain
      compared to the general population.

PMID- 25964127
TI  - A semi-analytical model for calculating the penetration depth of a high energy
      electron beam in a water phantom with a magnetic field.
AB  - PURPOSE: As an electron beam is incident on a uniform water phantom in the
      presence of a lateral magnetic field, the depth-dose distribution of the electron
      beam changes significantly and forms the well-known 'Bragg peak', with a depth
      dose distribution similar to that of heavy ions. This phenomenon has pioneered a
      new field in the clinical application of electron beams. For such clinical
      applications, evaluating the penetration depth of electron beams quickly and
      accurately is the critical problem. METHODS: This paper describes a model for
      calculating the penetration depth of an electron beam rapidly and correctly in a
      water phantom under the influence of a magnetic field. The model was used to
      calculate the penetration depths under different conditions: the energies of
      electron beams of 6, 8, 12 and 15 MeV and the magnetic induction intensities of
      0.75, 1.0, 1.5, 2.0 and 3.0 T. In addition, the calculation results were compared
      with the results of a Monte Carlo simulation. RESULTS: The comparison results
      indicate that the difference between the two calculation methods was less than
      0.5 cm. Moreover, the computing time of the calculation model was less than a
      second. CONCLUSIONS: The semi-analytical model proposed in the present study
      enables the penetration depth of the electron beam in the presence of a magnetic
      field to be obtained with a computational efficiency higher than that of the
      Monte Carlo approach; thus, the proposed model has high potential for
      application.

PMID- 25964128
TI  - Monte Carlo simulation of the dose distribution of ICRP adult reference
      computational phantoms for acquisitions with a 320 detector-row cone-beam CT
      scanner.
AB  - PURPOSE: The purpose of this study was to develop and validate a Monte Carlo (MC)
      simulation tool for patient dose assessment for a 320 detector-row CT scanner,
      based on the recommendations of International Commission on Radiological
      Protection (ICRP). Additionally, the simulation was applied on four clinical
      acquisition protocols, with and without automatic tube current modulation (TCM).
      METHODS: The MC simulation was based on EGS4 code and was developed specifically
      for a 320 detector-row cone-beam CT scanner. The ICRP adult reference phantoms
      were used as patient models. Dose measurements were performed free-in-air and
      also in four CTDI phantoms: 150 mm and 350 mm long CT head and CT body phantoms.
      The MC program was validated by comparing simulations results with these actual
      measurements acquired under the same conditions. The measurements agreed with the
      simulations across all conditions within 5%. Patient dose assessment was
      performed for four clinical axial acquisitions using the ICRP adult reference
      phantoms, one of them using TCM. RESULTS: The results were nearly always lower
      than those obtained from other dose calculator tools or published in other
      studies, which were obtained using mathematical phantoms in different CT systems.
      For the protocol with TCM organ doses were reduced by between 28 and 36%,
      compared to the results obtained using a fixed mA value. CONCLUSIONS: The
      developed simulation program provides a useful tool for assessing doses in a 320
      detector-row cone-beam CT scanner using ICRP adult reference computational
      phantoms and is ready to be applied to more complex protocols.

PMID- 25964129
TI  - Comprehensive quality assurance phantom for the small animal radiation research
      platform (SARRP).
AB  - PURPOSE: To develop and test the suitability and performance of a comprehensive
      quality assurance (QA) phantom for the Small Animal Radiation Research Platform
      (SARRP). METHODS AND MATERIALS: A QA phantom was developed for carrying out
      daily, monthly and annual QA tasks including: imaging, dosimetry and treatment
      planning system (TPS) performance evaluation of the SARRP. The QA phantom
      consists of 15 (60 * 60 * 5 mm(3)) kV-energy tissue equivalent solid water slabs.
      The phantom can incorporate optically stimulated luminescence dosimeters (OSLD),
      Mosfet or film. One slab, with inserts and another slab with hole patterns are
      particularly designed for image QA. RESULTS: Output constancy measurement results
      showed daily variations within 3%. Using the Mosfet in phantom as target, results
      showed that the difference between TPS calculations and measurements was within
      5%. Annual QA results for the Percentage depth dose (PDD) curves, lateral beam
      profiles, beam flatness and beam profile symmetry were found consistent with
      results obtained at commissioning. PDD curves obtained using film and OSLDs
      showed good agreement. Image QA was performed monthly, with image-quality
      parameters assessed in terms of CBCT image geometric accuracy, CT number
      accuracy, image spatial resolution, noise and image uniformity. CONCLUSIONS: The
      results show that the developed QA phantom can be employed as a tool for
      comprehensive performance evaluation of the SARRP. The study provides a useful
      reference for development of a comprehensive quality assurance program for the
      SARRP and other similar small animal irradiators, with proposed tolerances and
      frequency of required tests.

PMID- 25964130
TI  - Permanent pacemaker implanted into patient's left ventricle via subclavian artery
      by mistake: a case report.
AB  - BACKGROUND: Although various iatrogenic complications could be observed in the
      process of permanent pacemaker implantation, pacemaker electrode mistakenly
      implanted into left ventricle via subclavian artery and aortic valve has not been
      reported. CASE PRESENTATION: Herein, we reported a 71-year-old woman with
      permanent pacemaker mistakenly implanted into the left ventricle. During the
      operation of permanent pacemaker implantation, puncture was performed on her
      subclavian artery by mistake, and then the pacemaker electrode was put into the
      cardiac apex of left ventricle via ascending aorta reversely. CONCLUSION: The
      further operation could be conducted.

PMID- 25964131
TI  - Patient-Provider Therapeutic Alliance Contributes to Patient Activation in
      Community Mental Health Clinics.
AB  - Patient activation, often conceptualized as an individual trait, contributes to
      mental health outcomes. This study assessed the relational contributors to
      activation by estimating the longitudinal association of patient-provider
      communication and two factors of therapeutic alliance (agreement on tasks/goals
      and bond), with patient activation. Participants were patients (n = 264) from 13
      community-based mental health clinics across the United States. In multivariate
      models, controlling for patients' individual and clinical characteristics, the
      task/goal factor of therapeutic alliance emerged as a significant and independent
      predictor of greater change in patient activation scores. Improving patient
      activation may require addressing patient-provider interactions such as coming to
      collaborative agreement on the tasks/goals of care.

PMID- 25964132
TI  - Associations between climate variability, unemployment and suicide in Australia:
      a multicity study.
AB  - BACKGROUND: A number of studies have examined the associations of suicide with
      meteorological variables (MVs) and socioeconomic status but the results are
      inconsistent. This study assessed whether MVs and unemployment were associated
      with suicide in eight Australian capital cities. METHODS: Data on suicide,
      population and unemployment rate (UER) between 1985 and 2005 were from the
      Australian Bureau of Statistics. MVs was provided by Australian Bureau of
      Meteorology. A generalized linear regression model with Poisson link was applied
      to explore the association of suicide with MVs and UER. RESULTS: Temperature
      difference (DeltaT, the difference in mean temperature between current month and
      previous one month) was positively associated with suicide in Sydney, Melbourne,
      Brisbane and Hobart. There was also a significant and positive association
      between UER and suicide in Sydney, Melbourne, Brisbane and Perth. MVs had more
      significant associations with violent suicide than that of non-violent suicide.
      There were no consistent associations between other MVs and suicide. A
      significant interaction between DeltaT and UER on suicide was found in Sydney,
      Melbourne and Brisbane, such that increased temperature amplified the magnitude
      of the association between UER and suicide. CONCLUSIONS: DeltaT and UER appeared
      to jointly influence the occurrence of suicide in Australian capital cities. This
      finding may have implications for developing effective suicide prevention
      strategies.

PMID- 25964133
TI  - Vitamin D-related gene polymorphisms do not influence the outcome and serum
      vitamin D level in pegylated interferon/ribavirin therapy combined with protease
      inhibitor for patients with genotype 1b chronic hepatitis C.
AB  - Although several vitamin D-related gene polymorphisms were reported to affect the
      outcome of pegylated interferon/ribavirin (PR) therapy in chronic hepatitis C
      patients, there are no reports on the impact of the vitamin D-related gene
      polymorphisms in PR therapy combined with protease inhibitor (PI). Vitamin D
      related gene polymorphisms were determined in 177 genotype 1b-infected chronic
      hepatitis C patients who received 12 weeks of PR therapy with telaprevir, a first
      generation PI, followed by 12 weeks of PR therapy. The sustained virologic
      response (SVR) rate was 83.1% (147 of 177 patients). The frequencies of vitamin D
      related gene polymorphisms were: 83 non-TT and 94 TT genotypes for GC, 97 non-AA
      and 80 AA genotypes for DHCR7, 151 non-AA and 26 AA genotypes for CYP2R1, 162 non
      GG and 15 GG genotypes for CYP27B1, and 105 non-GG and 72 GG genotypes for VDR
      gene. Multivariate analysis extracted IL28B TT genotype (P = 2.05 * 10(-6)) and
      serum 25(OH) D3 level (P = 0.024) as independent factors contributing to the
      achieving of SVR. The SVR rate in IL28B TT genotype patients with serum 25(OH) D3
      level of < 25 ng/ml was significantly low compared to other patients. None of the
      vitamin D-related gene polymorphisms affected the treatment outcome and serum
      25(OH) D3 level. In conclusions, the IL28B polymorphism and serum 25(OH) D3 level
      contributed significantly and independently to SVR in PR combined with PI for
      genotype 1b-infected chronic hepatitis C patients. However, none of vitamin D
      related gene polymorphisms had an impact on the treatment outcome and serum
      25(OH) D3 level.

PMID- 25964134
TI  - Shedding light on inflammatory pseudotumor in children: spotlight on inflammatory
      myofibroblastic tumor.
AB  - Inflammatory pseudotumor is a generic term used to designate a heterogeneous
      group of inflammatory mass-forming lesions histologically characterized by
      myofibroblastic proliferation with chronic inflammatory infiltrate. Inflammatory
      pseudotumor is multifactorial in etiology and generally benign, but it is often
      mistaken for malignancy given its aggressive appearance. It can occur throughout
      the body and is seen in all age groups. Inflammatory pseudotumor has been
      described in the literature by many organ-specific names, resulting in confusion.
      Recently within this generic category of inflammatory pseudotumor, inflammatory
      myofibroblastic tumor has emerged as a distinct entity and is now recognized as a
      fibroblastic/myofibroblastic neoplasm with intermediate biological potential and
      occurring mostly in children. We present interesting pediatric cases of
      inflammatory myofibroblastic tumors given this entity's tendency to occur in
      children. Familiarity and knowledge of the imaging features of inflammatory
      pseudotumor can help in making an accurate diagnosis, thereby avoiding
      unnecessary radical surgery. 

PMID- 25964135
TI  - Hybrid Capture 2 human papillomavirus testing of fine needle aspiration cytology
      of head and neck squamous cell carcinomas.
AB  - BACKGROUND: Human papillomavirus (HPV) positive head and neck squamous cell
      carcinoma (HNSCC) accounts for 25% of HNSCCs and frequently presents with neck
      lymph node metastases. We investigated utilizing cytology needle rinse material
      for HPV DNA testing by Hybrid Capture 2 molecular testing (HC2) as an alternative
      to p16 immunohistochemistry. METHODS: Twenty-two cases of HNSCC presenting with
      neck lymph node metastasis were prospectively identified by assessment of Diff
      Quik stained cytology smears. An aliquot of the needle rinse material from the
      lymph node was analyzed for HPV status using standard HC2 protocol. P16 status
      was determined with immunohistochemistry on the cell block and/or surgically
      obtained tumor. RESULTS: The mean age of patients with p16 negative HNSCC was 7
      years older than p16 positive disease (Table ). Primary tumor subsites were as
      follows: 17 oropharynx, 1 hypophayrnx, 3 larynx, and 1 oral cavity (Table ). All
      ten p16 negative patients had a history of smoking compared with 33% of p16
      positive. Only 3 (25%) of p16 positive tumors demonstrated keratinization,
      whereas 90% of the p16 negative tumors keratinized (Fig. 1). Twelve of 22 HNSCC
      cases (55%) were p16 positive, of which 7 (58%) tested positive for HPV by HC2.
      Ten cases (45%) were negative for p16, all of which were negative for HPV by HC2
      (Table ). CONCLUSION: Molecular testing for HPV using HC2 on needle rinse
      material of FNA of HNSCC is a useful method of determining HPV status in HNSCC.

PMID- 25964136
TI  - Capillary electrophoresis for rapid identification of monoclonal antibodies for
      routine application in hospital.
AB  - mAbs are widely used in cancer therapy. Their compounding, performed just before
      their administration to patients, is executed in a production unit of the
      hospital. Identification of these drugs, individually prepared in bags for
      infusion before patient administration, is of paramount importance to detect
      potential mistakes during compounding stage. A fast and reliable analytical
      method based on CZE combined to a cationic capillary coating (hexadimethrine
      bromide) was developed for identification of the most widely used compounded
      therapeutic for cancer therapy (bevacizumab, cetuximab, rituximab, and
      trastuzumab). Considering the high structural and physico-chemical similarities
      of these mAbs, an extensive optimization of the BGE composition has been
      performed. The addition of perchlorate ions and polysorbate in the BGE greatly
      increased the resolution. To validate the method, an internal standard was used
      and the relative migration times (RTm) were estimated. Very satisfactory RSDs of
      the RTm for rituximab (0.76%), cetuximab (0.46%), bevacizumab (0.31%), and
      trastuzumab (0.60%) were obtained. The intraday and interday RSD of the method
      were less than 0.32 and 1.3%, respectively for RTm. Significant differences
      between theses RTms have been demonstrated allowing mAbs identification. Finally,
      accurate mAbs identification has been demonstrated by a blind test. 

PMID- 25964137
TI  - Moxifloxacin plus standard first-line therapy in the treatment of pulmonary
      tuberculosis: A meta-analysis.
AB  - The fluoroquinolone moxifloxacin has potent activity against Mycobacterium
      tuberculosis and has been recommended by the guidelines for the treatment of
      pulmonary tuberculosis (TB). Monotherapy is not recommended by the guidelines and
      only a few studies have evaluated the efficacy and safety of moxifloxacin plus
      standard first-line therapy in treating TB. The purpose of this meta-analysis was
      to further investigate the efficacy and safety of moxifloxacin plus standard
      therapy compared with standard therapy alone in treating patients with pulmonary
      TB. Medline, Cochrane, EMBASE and Google Scholar (until February 12, 2015) were
      searched for studies that evaluated the clinical efficacy and tolerability of
      moxifloxacin in the treatment of pulmonary TB. Rate of culture conversion and
      serious adverse events (SAEs) were assessed. Risk of bias and sensitivity
      analysis, using the leave-one-out approach, was used to assess the robustness of
      the findings. Six studies were included in the meta-analysis which covered 2056
      patients with pulmonary TB. For all included studies, the drug regimens at least
      contained rifampicin and pyrazinamide and the length of treatment was at least
      eight weeks. The odds ratio (OR) for the negative culture rate for moxifloxacin
      plus first-line medications compared first-line medications alone (the control
      group) was 1.60 with 95% CI in 0.93-2.74 (P = 0.089), indicating the moxifloxacin
      plus first-line medications had no significantly greater rate of culture
      conversion compared with first-line medication alone. The odds ratio of SAEs for
      moxifloxacin plus first-line medications compared with first-line medications
      alone found no difference in rate of SAEs between treatment groups (OR = 0.94, P
      = 0.862). In conclusion, our meta-analysis suggests that there was a trend for
      the addition of moxifloxacin to standard first-line therapy for non-drug
      resistant TB resulted to increase the rate of culture conversion but this effect
      requires confirmation in more randomized control trials. 

PMID- 25964138
TI  - The prevalence and risk factors of Post-Traumatic Stress Disorder among workers
      injured in Rana Plaza building collapse in Bangladesh.
AB  - OBJECTIVES: Prevalence and risk factors of PTSD among injured garment workers who
      survived a major factory collapse. METHODS: Survivors receiving treatment or
      rehabilitation care at one year post event were surveyed, which included Post
      Traumatic Stress Disorder Checklist Specific version. RESULTS: The respondents
      consisted of 181 people with a mean age of 27.8 years and a majority had less
      than high school education (91.2%). Multivariable logistic regression found that
      the odds of having PTSD was higher among married (OR: 3.2 [95% CI: 1.3-8.0]),
      those who used to work more than 70 hr/week (OR: 2.4 [1.1-5.3]), workers who used
      to hold higher job positions (OR: 2.6 [1.2-5.6]) or who had a concussion injury
      (OR: 3.7 [1.4-9.8]). Among the respondents, 83.4% remained unemployed, and only
      57.3% (63 people) reported receiving a quarter or less of what they were promised
      as compensation. CONCLUSIONS: Probable PTSD was prevalent among surviving workers
      of the Rana Plaza building collapse in Bangladesh.

PMID- 25964139
TI  - Development and evaluation of a pocket card to support prescribing by junior
      doctors in an English hospital.
AB  - BACKGROUND: Junior doctors do most inpatient prescribing, with a relatively high
      error rate, and locally had reported finding prescribing very stressful.
      OBJECTIVE: To develop an intervention to improve Foundation Year 1 (FY1) doctors'
      experience of prescribing, and evaluate their satisfaction with the intervention
      and perceptions of its impact. METHODS: Based on findings of a focus group and
      questionnaire, we developed a pocket Dose Reference Card ("Dr-Card") for use at
      the point of prescribing. This summarised common drugs and dosing schedules and
      was distributed to all new FY1 doctors in a London teaching trust. A post
      intervention questionnaire explored satisfaction and perceived impact. RESULTS:
      Focus group participants (n = 12) described feeling anxious and time pressured
      when prescribing; a quick reference resource for commonly prescribed drug doses
      was suggested. Responses to the exploratory questionnaire reinforced these
      findings. Following Dr-Card distribution, the post-intervention questionnaire
      revealed that 29/38 (76 %) doctors were still using it 2 months after
      distribution and 38/38 (100%) would recommend ongoing production. CONCLUSIONS:
      FY1 doctors reported feeling stressed and time pressured when prescribing; this
      was perceived to contribute to error. A pocket card presenting common drugs and
      doses was well-received, perceived to be useful, and recommended for on-going
      use.

PMID- 25964140
TI  - The influence of pharmacy and pharmacist characteristics on the secondary
      prevention of cardiovascular disease.
AB  - BACKGROUND: A range of extended/enhanced pharmacy services (EPS) are increasingly
      being offered in community pharmacies following a global paradigm shift in
      professional pharmacy practice from a product-oriented focus to a patient
      centered approach. A number of pharmacy/pharmacist characteristics have been
      reported to influence EPS provision. OBJECTIVE: To investigate the association
      between EPS provision and community pharmacists' support in CVD secondary
      prevention and to identify pharmacy/pharmacist characteristics which predict EPS
      provision and CVD support. Setting Australian community pharmacies. METHODS: Mail
      surveys to 1350 randomly selected pharmacies, stratified by state/territory,
      exploring professional activities provided to clients with CVD, characteristics
      of pharmacies (including EPS provision), and pharmacist characteristics. The
      survey data were analyzed using univariate analyses and multiple linear
      regression analysis. MAIN OUTCOME MEASURE: The level of community pharmacists'
      CVD support, determined by summing respondents' score for seven CVD support
      related activities, and the pharmacies' level of involvement in EPS provision,
      determined by summing respondents' score for four types of EPS. EPS provision was
      then used as an independent variable in the regression analysis of CVD support.
      RESULTS: A response rate of 15.8% (209/1320) was obtained after three waves of
      the survey. Pharmacy documentation, a private area, Quality Care Pharmacy Program
      accreditation, number of pharmacists, and pharmacists' resource adequacy were
      predictors of EPS provision (adjusted R2 = 0.299, p < 0.001). The provision of
      CVD support was predicted by EPS provision (beta = 0.290, p < 0.001),
      pharmacists' frequent contacts with general practitioners (beta = 0.298, p <
      0.001), and pharmacy documentation (beta = 0.134, p = 0.033). The regression
      model of CVD support explained 34.2% of the variation (p < 0.001). CONCLUSION:
      Community pharmacists could contribute to CVD secondary prevention if they had
      frequent contacts with general practitioners and worked in pharmacies with a
      higher level of involvement in EPS provision. Of all influencing factors,
      documentation was a predictor of both EPS provision and CVD support, indicating
      the importance of documentation in supporting the management of chronic
      conditions.

PMID- 25964143
TI  - Chiroptical vesicles and disks that originated from achiral molecules.
AB  - We report a chiral gel of vesicles and disklike micelles that originated from
      achiral molecules. The supramolecular chirality was obtained via regulating pH,
      in which a sol-gel-sol transition in a colloidal system consisting of a gelator,
      4,4-di(2,3-dicarboxylphenoxyl)azobenzene (AzoNa4), and a zwitterionic surfactant,
      tetradecyldimethylamine oxide (C14DMAO), happened. The supramolecular chirality
      was related to the state of aggregation, i.e., only the condensed gels show
      chiral sense and sols are chiral-silent. The coexistence of vesicles and disklike
      micelles was captured for the first time in supramolecular chiral hydrogels by
      cryo- and freeze-fracture transmission electron microscopy (cryo- and FF-TEM)
      observations. Ascribed to the photoisomerization of the azobenzene units, upon
      alternative UV/visible light irradiation, the gel chirality can be switched
      reversibly with the macroscopic changes between vesicles/disks and wormlike
      micelles. A pH- and light-dual-responsive chiroptical switch can be constructed,
      which may require understanding the regulating membrane permeability and reagent
      release of structural transformation through photoisomerization and also require
      understanding the origin of gelation-induced supramolecular chirality completely
      based on achiral molecules. 

PMID- 25964141
TI  - Extracellular vesicles such as prostate cancer cell fragments as a fluid biopsy
      for prostate cancer.
AB  - Extracellular vesicles (EVs) are cell-derived vesicles generated through a
      process of cell membrane shedding or storage vesicle release, as occurs during
      apoptosis, necrosis or exocytosis. Initially perceived as cellular by-products or
      'dust' of insignificant biological importance, recent research has shed light on
      the role of EVs as mediators of intercellular communication, blood coagulation
      and disease progression. The prostate is a source of EVs and their abundance in
      complex biological fluids such as plasma, serum and urine make them compelling
      entities for a 'fluid biopsy'. As such, prostate cancer cell fragments (PCCF) are
      EVs generated by the tumor resident within the prostate and are also present in
      blood, expressing a portion of biomarkers representative of the primary tumor.
      High-throughput analytical techniques to determine biomarker expression on EVs is
      the last hurdle towards translating the full potential of prostate EVs for
      clinical use. We describe current state-of-the-art methods for the analysis of
      prostate-derived EVs in patient fluids such as plasma and the challenges that lie
      ahead in this emerging field of translational research. 

PMID- 25964144
TI  - A Spur to Atavism: Placing Platypus Poison.
AB  - For over two centuries, the platypus (Ornithorhynchus anatinus) has been
      constructed and categorized in multiple ways. An unprecedented melange of
      anatomical features and physiological functions, it long remained a systematic
      quandary. Nevertheless, since 1797, naturalists and biologists have pursued two
      recurring obsessions. Investigations into platypus reproduction and lactation
      have focused attention largely upon females of the species. Despite its apparent
      admixture of avian, reptilian and mammalian characters, the platypus was soon
      placed as a rudimentary mammal--primitive, naive and harmless. This article
      pursues a different taxonomic trajectory, concentrating on a specifically male
      anatomical development: the crural spur and venom gland on the hind legs. Once
      the defining characteristic of both the platypus and echidna (Tachyglossus
      aculeatus), by 1830 this sexed spur had been largely dismissed as inactive and
      irrelevant. For a creature regularly depicted as a biological outlier, the
      systematic and evolutionary implications of platypus poison have remained largely
      overlooked. In Australia, however, sporadic cases of 'spiking' led to consistent
      homologies being remarked between the platypus crural system and the venom glands
      of snakes. As with its reproductive reliance upon eggs, possession of an
      endogenous poison suggested significant reptilian affinities, yet the platypus
      has rarely been classed as an advanced reptile. Indeed, ongoing uncertainty
      regarding the biological purpose of the male's spur has ostensibly posed a
      directional puzzle. As with so many of its traits, however, platypus poison has
      been consistently described as a redundant remnant, rather than an emergent
      feature indicating evolutionary advance.

PMID- 25964142
TI  - Devices for dry powder drug delivery to the lung.
AB  - Dry powder inhalers (DPIs) are an important and increasingly investigated method
      of modern therapy for a growing number of respiratory diseases. DPIs are a
      promising option for certain patient populations, and may help to overcome
      several limitations that are associated with other types of inhalation delivery
      systems (e.g., accuracy and reproducibility of the dose delivered, compliance and
      adherence issues, or environmental aspects). Today, more than 20 different dry
      powder inhalers are on the market to deliver active pharmaceutical ingredients
      (APIs) for local and/or systemic therapy. Depending on the mechanism of
      deagglomeration, aerosolization, dose metering accuracy, and the interpatient
      variability, dry powder inhalers demonstrate varying performance levels. During
      development, manufacturers focus on improving aspects characteristic of their
      specific DPI devices, depending on the intended type of application and any
      particular requirements associated with it. With the wide variety of applications
      related to specific APIs, there exists a range of different devices with distinct
      features. In addition to the routinely used multi-use DPIs, several single-use
      disposable devices are under development or already approved. The recent
      introduction of disposable devices will expand the range of possible applications
      for use by including agents such as vaccines, analgesics, or even rescue
      medications. This review article discusses the performance and advantages of
      recently approved dry powder inhalers as well as disposable single-use inhalers
      that are currently under development. 

PMID- 25964145
TI  - Bishop Score vs. ultrasound cervical length in the prediction of cervical
      ripening success and vaginal delivery in nulliparous women.
AB  - AIM: The aim of this paper was to compare the predictive value of Bishop Score
      and sonographic measurement of cervical length for predicting cervical ripening
      success and vaginal delivery in nulliparous women with low Bishop Score. METHODS:
      A prospective observational study including 77 nulliparous pregnant women at
      exactly 41 weeks of gestation with a Bishop Score <= 5. Cervical measurement was
      performed by transvaginal ultrasonography and Bishop Score was determined by
      digital examination. All patients had cervical ripening with Prostaglandins prior
      to labor induction with oxytocin. RESULTS: Cervical ripening was successful in 63
      patients (81%) and vaginal delivery occurred in 51 women (66.2%). Multiple
      logistic regression analysis demonstrated cervical length assessed by
      transvaginal sonography as the only independent predictor of successful cervical
      ripening and vaginal delivery. The best cut-off point was 34.6 for predicting
      successful cervical ripening and 32.5 mm for predicting vaginal delivery. The
      chance of vaginal delivery was 90% when initial cervical length was < 32.5 mm and
      50% when cervical length was >32.5 mm. CONCLUSION: Compared with the Bishop
      score, ultrasound cervical length measurement is a better predictor of cervical
      ripening success and vaginal delivery in nulliparous women at 41 weeks of
      gestation with an unfavorable cervix.

PMID- 25964146
TI  - Synthesis of highly fluorescent nitrogen and phosphorus doped carbon dots for the
      detection of Fe(3+) ions in cancer cells.
AB  - Highly fluorescent nitrogen and phosphorus-doped carbon dots with a quantum yield
      59% have been successfully synthesized from citric acid and di-ammonium hydrogen
      phosphate by single step hydrothermal method. The synthesized carbon dots have
      high solubility as well as stability in aqueous medium. The as-obtained carbon
      dots are well monodispersed with particle sizes 1.5-4 nm. Owing to a good tunable
      fluorescence property and biocompatibility, the carbon dots were applied for
      intercellular sensing of Fe(3+) ions as well as cancer cell imaging.

PMID- 25964148
TI  - Synthesis of deleobuvir, a potent hepatitis C virus polymerase inhibitor, and its
      major metabolites labeled with carbon-13 and carbon-14.
AB  - Deleobuvir, (2E)-3-(2-{1-[2-(5-bromopyrimidin-2-yl)-3-cyclopentyl-1-methyl-1H
      indole-6-carboxamido]cyclobutyl}-1-methyl-1H-benzimidazol-6-yl)prop-2-enoic acid
      (1), is a non-nucleoside, potent, and selective inhibitor of hepatitis C virus
      NS5B polymerase. Herein, we describe the detailed synthesis of this compound
      labeled with carbon-13 and carbon-14. The synthesis of its three major
      metabolites, namely, the reduced double bond metabolite (2) and the acyl
      glucuronide derivatives of (1) and (2), is also reported. Aniline-(13) C6 was the
      starting material to prepare butyl (E)-3-(3-methylamino-4-nitrophenyl-(13) C6
      )acrylate [(13) C6 ]-(11) in six steps. This intermediate was then used to obtain
      [(13) C6 ]-(1) and [(13) C6 ]-(2) in five and four more steps, respectively. For
      the radioactive synthesis, potassium cyanide-(14) C was used to prepare 1
      cylobutylaminoacid [(14) C]-(23) via Buchrer-Bergs reaction. The carbonyl
      chloride of this acid was then used to access both [(14) C]-(1) and [(14) C]-(2)
      in four steps. The acyl glucuronide derivatives [(13) C6 ]-(3), [(13) C6 ]-(4)
      and [(14) C]-(3) were synthesized in three steps from the acids [(13) C6 ]-(1),
      [(13) C6 ]-(2) and [(14) C]-(1) using known procedures. 

PMID- 25964149
TI  - Neglected zoonoses: forgotten infections among disregarded populations.

PMID- 25964147
TI  - Anti-proliferative and pro-apoptotic effects of lichen-derived compound
      protolichesterinic acid are not mediated by its lipoxygenase-inhibitory activity.
AB  - Lipoxygenases (LOXs) and their products are involved in several biological
      functions and have been associated with carcinogenesis. Protolichesterinic acid
      (PA), a lichen metabolite, inhibits 5- and 12-LOX and has anti-proliferative
      effects on various cancer cell lines. Here, PA was shown to inhibit proliferation
      of multiple myeloma cells, RPMI 8226 and U266, and pancreatic cancer cells AsPC
      1. Apoptosis was induced only in multiple myeloma cells. Cell-cycle associated
      changes in expression and sub-cellular localization of 5- and 12-LOX were not
      affected by PA but increased cytoplasmic localisation was found to accompany
      morphological changes at later stages. Assessment by mass spectrometry showed
      that PA entered the pancreatic cancer cells. However, effects on LOX metabolites
      were only evident after treatment with concentrations exceeding those having anti
      proliferative effects and no effects were measurable in the myeloma cells. We
      conclude that the anti-proliferative and pro-apoptotic effects of PA are not
      mediated directly through inhibition of LOX activity. 

PMID- 25964150
TI  - Reply: Epidemiologic studies need asymptomatic controls.

PMID- 25964151
TI  - Unexpectedly high prevalence of Treponema pallidum infection in the oral cavity
      of human immunodeficiency virus-infected patients with early syphilis who had
      engaged in unprotected sex practices.
AB  - Between 2010 and 2014, we obtained swab specimens to detect Treponema pallidum,
      with PCR assays, from the oral cavities of 240 patients with 267 episodes of
      syphilis who reported engaging in unprotected sex practices. The detected
      treponemal DNA was subjected to genotyping. All of the syphilis cases occurred in
      men who have sex with men (MSM), and 242 (90.6%) occurred in human
      immunodeficiency virus-infected patients. The stages of syphilis included 38
      cases (14.2%) of primary syphilis of the genital region, 76 (28.5%) of secondary
      syphilis, 21 (7.9%) of primary and secondary syphilis, 125 (46.8%) of early
      latent syphilis, and seven (2.6%) others. Concurrent oral ulcers were identified
      in 22 cases (8.2%). Treponemal DNA was identified from the swabs of 113 patients
      (42.2%), including 15 (68.2%) with oral ulcers. The most common genotype of T.
      pallidum was 14f/f. The presence of oral ulcers was associated with
      identification of T. pallidum in the swab specimens (15/22 (68.2%) vs. 98/245
      (40.0%)) (p = 0.01). In multivariate analysis, secondary syphilis (adjusted OR
      6.79; 95% CI 1.97-23.28) and rapid plasma reagin (RPR) titres of >=1: 32
      (adjusted OR 2.23; 95% CI 1.02-4.89) were independently associated with the
      presence of treponemal DNA in patients without oral ulcers. We conclude that
      detection of treponemal DNA in the oral cavity with PCR assays is not uncommon in
      MSM, most of whom reported having unprotected oral sex. Although the presence of
      oral ulcers is significantly associated with detection of treponemal DNA,
      treponemal DNA is more likely to be identified in patients without oral ulcers
      who present with secondary syphilis and RPR titres of >=1: 32.

PMID- 25964153
TI  - Molecular epidemiology of severe respiratory disease by human rhinoviruses and
      enteroviruses at a tertiary paediatric hospital in Barcelona, Spain.
AB  - In order to describe the molecular epidemiology of human rhinovirus (HRV) and
      enterovirus (EV) infection in severely ill children, we studied all episodes of
      bronchospasm/bronchopneumonia in 6-month-old to 18-year-old patients from January
      2010 to May 2012 who required mechanical ventilation. HRV/EVs were detected in 55
      (57.3%) of 96 patients, of which 50 (91%) were HRV (HRV-A, 16; HRV-B, 1; HRV-C,
      18) and 5 (9%) were EVs (EV-D68, 3). No significant differences in epidemiologic
      and clinical characteristics were found between different types. In six of the 13
      patients who required invasive mechanical ventilation, HRV was the only pathogen
      detected. 

PMID- 25964152
TI  - Neglected bacterial zoonoses.
AB  - Bacterial zoonoses comprise a group of diseases in humans or animals acquired by
      direct contact with or by oral consumption of contaminated animal materials, or
      via arthropod vectors. Among neglected infections, bacterial zoonoses are among
      the most neglected given emerging data on incidence and prevalence as causes of
      acute febrile illness, even in areas where recognized neglected tropical diseases
      occur frequently. Although many other bacterial infections could also be
      considered in this neglected category, five distinct infections stand out because
      they are globally distributed, are acute febrile diseases, have high rates of
      morbidity and case fatality, and are reported as commonly as malaria, typhoid or
      dengue virus infections in carefully designed studies in which broad-spectrum
      diagnoses are actively sought. This review will focus attention on leptospirosis,
      relapsing fever borreliosis and rickettsioses, including scrub typhus, murine
      typhus and spotted fever group rickettsiosis. Of greatest interest is the lack of
      distinguishing clinical features among these infections when in humans, which
      confounds diagnosis where laboratory confirmation is lacking, and in regions
      where clinical diagnosis is often attributed to one of several perceived more
      common threats. As diseases such as malaria come under improved control, the real
      impact of these common and under-recognized infections will become evident, as
      will the requirement for the strategies and allocation of resources for their
      control. 

PMID- 25964154
TI  - Clostridium difficile toxin testing by National Health Service (NHS) acute Trusts
      in England: 2008-2013.
AB  - In October 2007, a governmental 3-year target to reduce Clostridium difficile
      infection (CDI) by 30%, with financial penalties levied for failure, was
      introduced in England. This target was met within just 1 year, leading to
      speculation of 'gaming', with hospitals empirically treating possible CDI in the
      absence of a microbiological diagnosis, to avoid having to report confirmed
      cases. An analysis of aggregate mandatory data on levels of testing for C.
      difficile toxin showed little evidence of a fall in testing during the steepest
      infection rate reductions, suggesting that this was not a major factor in the
      decline in CDI.

PMID- 25964155
TI  - Epidemiologic studies need asymptomatic controls.

PMID- 25964156
TI  - [Hypercholesterolaemic xanthomas in a 14-year-old boy].

PMID- 25964157
TI  - [Needs, uses, cons-pros, good practices and opportunities about walker in elderly
      with loss of autonomy].
AB  - Non-use of the walker may be secondary to an initial inappropriate prescribing, a
      lack of adequate training, a lack of monitoring and side effects of using.
      Improving both stability and mobility in users is due to several biomechanical
      mechanisms. The benefits of walker are: general physiological effects, more
      confidence, better social life and decrease in the burden of care. The
      disadvantages of walker are: technical or practical aspects criticized by users,
      musculoskeletal disorders, delayed reaction time, fall risk and stigma. Few
      scientific data evaluating the interest of the walker concerning mobility exist,
      thus recommendations are low grade and are often taken from professional clinical
      experiences. The choice of technical walking assistance depends on the pathology
      and biomechanical mechanism. The walker robots are few distributed. 

PMID- 25964158
TI  - Plant products impairing fertility of animals.

PMID- 25964159
TI  - Thiols as interfacial modifiers to enhance the performance and stability of
      perovskite solar cells.
AB  - Modifying the interfaces of CH3NH3PbI3 with TiO2 and hole transport layers using
      two different types of thiols leads to enhanced performance and stability of
      perovskite solar cells. The incorporation of HOOC-Ph-SH at the TiO2/perovskite
      interface facilitates electron transfer from perovskite to TiO2 and also alters
      the morphology of perovskite crystal growth to increase the power conversion
      efficiency. The modification of pentafluorobenzenethiol at the perovskite/hole
      transport layer interface improves the stability. 

PMID- 25964160
TI  - Ecosystem services in coupled social-ecological systems: Closing the cycle of
      service provision and societal feedback.
AB  - Both the 'cascade model' of ecosystem service provision and the Driver-Pressure
      State-Impact-Response framework individually contribute to the understanding of
      human-nature interactions in social-ecological systems (SES). Yet, as several
      points of criticism show, they are limited analytical tools when it comes to
      reproducing complex cause-effect relationships in such systems. However, in this
      paper, we point out that by merging the two models, they can mutually enhance
      their comprehensiveness and overcome their individual conceptual deficits.
      Therefore we closed a cycle of ecosystem service provision and societal feedback
      by rethinking and reassembling the core elements of both models. That way, we
      established a causal sequence apt to describe the causes of change to SES, their
      effects and their consequences. Finally, to illustrate its functioning we
      exemplified and discussed our approach based on a case study conducted in the
      Alpujarra de la Sierra in southern Spain. 

PMID- 25964161
TI  - The long-term outcomes of physiologic repair for ccTGA (congenitally corrected
      transposition of the great arteries).
AB  - PURPOSE: The short-term outcome of physiologic repair for congenitally corrected
      transposition of the great arteries (ccTGA) is generally considered favorable;
      however, the long-term outcome is the greatest problem, especially with regard to
      right ventricular (RV) function and tricuspid regurgitation (TR). Although
      tricuspid valve replacement (TVR) appears to be a realistic choice for treating
      severe TR, determining the timing of TVR may be difficult. METHODS: We carried
      out a retrospective analysis of the long-term outcomes of physiologic repair for
      ccTGA focusing on patients with TVR. The study involved 23 patients after
      physiologic repair 10 or more years prior. There were 9 TVR cases in 5 pediatric
      patients (before age 18) and 4 adult patients. RESULTS: There were two late
      deaths; however, there was no case related with cardiac events. Overall survival
      at 10 and 20 years were 95.5 and 90.2 %, respectively, and 7 of 8 patients after
      TVR were NYHA class I or II. No patient has presented postoperative complications
      in the form of bleeding or embolism after TVR with mechanical valve. CONCLUSIONS:
      An analysis of the results of physiologic repair for ccTGA showed that the long
      term outcome was overall favorable. To maintain RV function, early TVR may be a
      reasonable option, even in the management of patients during childhood.

PMID- 25964162
TI  - Cystine-knot peptides targeting cancer-relevant human cytotoxic T lymphocyte
      associated antigen 4 (CTLA-4).
AB  - Cystine-knot peptides sharing a common fold but displaying a notably large
      diversity within the primary structure of flanking loops have shown great
      potential as scaffolds for the development of therapeutic and diagnostic agents.
      In this study, we demonstrated that the cystine-knot peptide MCoTI-II, a trypsin
      inhibitor from Momordica cochinchinensis, can be engineered to bind to cytotoxic
      T lymphocyte-associated antigen 4 (CTLA-4), an inhibitory receptor expressed by T
      lymphocytes, that has emerged as a target for the treatment of metastatic
      melanoma. Directed evolution was used to convert a cystine-knot trypsin inhibitor
      into a CTLA-4 binder by screening a library of variants using yeast surface
      display. A set of cystine-knot peptides possessing dissociation constants in the
      micromolar range was obtained; the most potent variant was synthesized
      chemically. Successive conjugation with neutravidin, fusion to antibody Fc domain
      or the oligomerization domain of C4b binding protein resulted in oligovalent
      variants that possessed enhanced (up to 400-fold) dissociation constants in the
      nanomolar range. Our data indicate that display of multiple knottin peptides on
      an oligomeric scaffold protein is a valid strategy to improve their functional
      affinity with ramifications for applications in diagnostics and therapy.

PMID- 25964163
TI  - Psychological Inflexibility and Psychopathology in 9-1-1 Telecommunicators.
AB  - Mental health in 9-1-1 telecommunicators has been understudied in comparison to
      other emergency responders. This study enrolled a sample of telecommunicators
      from across the United States (N = 808). As measured by self-report, the
      prevalence of current probable posttraumatic stress disorder (PTSD) was 17.6% to
      24.6%; it was 23.9% for probable major depression. Structural equation modeling
      revealed a significant direct effect of psychological inflexibility on
      psychopathology (path coefficient = .32) when considered among duty-related
      distress and dissociation, neuroticism, anger, and emotion dysregulation. The
      results provided further evidence of the adverse psychological effects of duty
      related trauma exposure, including exposure that is vicarious in nature. The
      results indicate a need for prevention and intervention in this population, with
      psychological inflexibility as a potential target in these efforts. 

PMID- 25964164
TI  - Experience of brentuximab vedotin in relapsed/refractory Hodgkin lymphoma and
      relapsed/refractory systemic anaplastic large-cell lymphoma in the Named Patient
      Program: Review of the literature.
AB  - Brentuximab vedotin was made available via a Named Patient Program (NPP) to non
      US/Canadian patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL) or
      systemic anaplastic large-cell lymphoma (sALCL) until approval in their
      respective countries. We re-evaluated the efficacy and safety NPP data in a
      pooled analysis. Through a systematic literature review, 21 NPP publications were
      identified describing 14 cohorts (N=245). Among patients with a specified
      diagnosis, 207 had HL, 28 had ALCL, and one had CD30+ T-cell lymphoma (not
      specified). In cohorts reporting response, overall response and complete
      remission rates were 67% and 26%, respectively, in R/R HL, and 75% and 74%,
      respectively, in R/R ALCL. Incidences of grade 3/4 neurologic and hematologic
      toxicities were 6% and 12%, respectively; 5% of patients discontinued because of
      toxicity. In real-world practice, response rates and tolerability to brentuximab
      vedotin are similar to those reported in the two pivotal phase 2 trials in these
      settings. 

PMID- 25964166
TI  - Both binding and blocking antibodies correlate with disease severity in
      myasthenia gravis.
AB  - Myasthenia gravis (MG) is an autoimmune disease associated with antibodies
      directed to the postsynaptic muscle components of the neuromuscular junction. The
      heterogeneous nature of the acetylcholine receptor (AChR) antibody response had
      led to the categorization of AChR antibodies into 3 types: binding, blocking, and
      modulating antibodies. The purpose of this study is to compare the AChR
      antibodies' type with the clinical severity of MG patients. The patients enrolled
      in the study had been tested for both binding and blocking antibodies and had
      disease duration exceeding 2 years since diagnosis. The patients were divided
      into five main classes by the Myasthenia Gravis Foundation of America clinical
      classification. Again, the enrolled patients were divided into ocular and
      generalized group. We compared the type and titer of antibodies and the thymus
      status between the ocular and generalized group. Thirty-five patients met the
      inclusion criteria. Of these, 16 patients (47 %) had both blocking and binding
      AChR antibodies, 11 patients (31 %) had only binding antibodies, and 8 patients
      (22 %) had only blocking antibodies. By defined clinical classification, the
      ocular and generalized groups included 10 and 25 patients, respectively. Sixteen
      patients in the generalized group possessed both AChR antibodies, with the
      remaining patients displaying only the binding antibody. All the patients with
      only blocking antibody were classified into ocular group. Use of binding and
      blocking antibodies' tests may, therefore, be more helpful in predicting the
      prognosis and diagnoses of MG patient.

PMID- 25964165
TI  - Estrogen amelioration of Abeta-induced defects in mitochondria is mediated by
      mitochondrial signaling pathway involving ERbeta, AKAP and Drp1.
AB  - Perturbations in dynamic properties of mitochondria including fission, fusion,
      and movement lead to disruption of energy supply to synapses contributing to
      neuropathology and cognitive dysfunction in Alzheimer's disease (AD). The
      molecular mechanisms underlying these defects are still unclear. Previously, we
      have shown that ERbeta is localized in the mitochondria and ERbeta knock down
      disrupts mitochondrial functions. Because a selective ERbeta modulator (DPN) can
      activate PKA, and localized PKA signaling in the mitochondrial membrane regulates
      mitochondrial structure and functions, we reasoned that ERbeta signaling in the
      mitochondrial membrane rescues many of the mitochondrial defects caused by
      soluble Abeta oligomer. We now report that DPN treatment in primary hippocampal
      neurons attenuates soluble Abeta-oligomer induced dendritic mitochondrial fission
      and reduced mobility. Additionally, Abeta treatment reduced the respiratory
      reserve capacity of hippocampal neuron and inhibited phosphorylation of Drp1 at
      its PKA site, which induces excessive mitochondrial fission, and DPN treatment
      ameliorates these inhibitions. Finally, we discovered a direct interaction of
      ERbeta with a mitochondrial resident protein AKAP1, which induces the PKA
      mediated local signaling pathway involved in increased oxidative phosphorylation
      and inhibition of mitochondrial fission. Taken together, our findings highlight
      the possibility that ERbeta signaling pathway may be a useful mitochondria
      directed therapeutic target for AD.

PMID- 25964167
TI  - A cross-cultural comparison of folk plant uses among Albanians, Bosniaks, Gorani
      and Turks living in south Kosovo.
AB  - BACKGROUND: Kosovo represents a unique hotspot of biological and cultural
      diversity in Europe, which allows for interesting cross-cultural ethnobotanical
      studies. The aims of this study were twofold: 1) to document the state of
      traditional knowledge related to local (esp. wild) plant uses for food, medicine,
      and handicrafts in south Kosovo; and 2) to examine how communities of different
      ethnic groups in the region (Albanians, Bosniaks/Gorani, and Turks) relate to and
      value wild botanical taxa in their ecosystem. METHODS: Field research was
      conducted in 10 villages belonging to the Prizren municipality and 4 villages
      belonging to the Dragash municipality, located in the Sharr Mountains in the
      southern part of Kosovo. Snowball sampling techniques were used to recruit 139
      elderly informants (61 Albanians, 32 Bosniaks/Gorani and 46 Turks), for
      participation in semi-structured interviews regarding the use of the local flora
      for medicinal, food, and handicraft purposes. RESULTS: Overall, we recorded the
      local uses of 114 species were used for medicinal purposes, 29 for food (wild
      food plants), and 20 in handicraft activities. The most important species used
      for medicinal purposes were Achillea millefolium L., Sambucus nigra L., Urtica
      dioica L., Tilia platyphyllos Scop. Hypericum perforatum L., Chamomilla recutita
      (L.) Rauschert, Thymus serpyllum L. and Vaccinium myrtillus L. Chamomilla
      recutita was the most highly valued of these species across the populations
      surveyed. Out of 114 taxa used for medicinal purposes, only 44 species are also
      included in the European Pharmacopoeia. The predominantly quoted botanical
      families were Rosaceae, Asteraceae, and Lamiaceae. Comparison of the data
      recorded among the Albanian, Bosniak/Gorani, and Turkish communities indicated a
      less herbophilic attitude of the Albanian populations, while most quoted taxa
      were quoted by all three communities, thus suggesting a hybrid character of the
      Kosovar plant knowledge. CONCLUSION: Cross-cultural ethnobiological studies are
      crucial in the Balkans not only for proposing ways of using plant natural
      resources, which could be exploited in sustainable local development projects
      (e.g. focusing on eco-tourism and small-scale trade of medicinal herbs, food
      niche and handicrafts products), but also for fostering collaboration and
      reconciliation among diverse ethnic and religious communities.

PMID- 25964168
TI  - Safety, tolerability, and immunogenicity of zoster vaccine in subjects on
      chronic/maintenance corticosteroids.
AB  - BACKGROUND: This randomized, placebo-controlled study assessed the safety,
      tolerability, and immunogenicity of live virus zoster vaccine (ZV) in individuals
      receiving chronic/maintenance systemic corticosteroid therapy (daily dose
      equivalent of 5-20mg prednisone) for >=2 weeks prior to vaccination and >=6 weeks
      postvaccination. METHODS: Subjects were followed for adverse experiences (AEs),
      exposure to varicella or herpes zoster (HZ), or development of
      varicella/varicella-like or HZ/HZ-like rashes for 42 days postvaccination
      (primary safety follow-up period) and for serious AEs (SAEs) through Day 182
      postvaccination (secondary follow-up period). Varicella-zoster virus (VZV)
      antibody titers by glycoprotein enzyme-linked immunosorbent assay (gpELISA) were
      measured at baseline and at Week 6 postvaccination. RESULTS: The proportions of
      subjects reporting systemic AEs and SAEs were similar in both groups. A higher
      percentage of subjects reported injection-site AEs in the ZV group (21.5%) than
      in the placebo group (12.1%). One SAE of ophthalmic HZ (onset Day 16
      postvaccination) was reported in the ZV group and deemed vaccine-related by the
      study investigator; however, PCR testing confirmed the presence of wild-type (not
      vaccine strain) VZV. Geometric mean titer (GMT) at 6 weeks postvaccination was
      higher for ZV recipients than placebo recipients, with estimated geometric mean
      fold rises (GMFR) of 2.3 (CI: 2.0, 2.7) and 1.1 (CI: 1.0, 1.2) respectfully.
      CONCLUSIONS: In adults >=60 years old on chronic/maintenance corticosteroids, ZV
      was generally well tolerated and immunogenic. The VZV-specific gpELISA antibody
      GMT at 6 weeks postvaccination and the GMFR from baseline to 6 weeks
      postvaccination were higher in the ZV group than in the placebo group.

PMID- 25964169
TI  - Clinical performance and safety of adapters for intradermal delivery with
      conventional and autodisable syringes.
AB  - Although the number of vaccines and diagnostic tests currently delivered
      intradermally is limited, this route of administration offers potential
      advantages due to the high concentration of antigen-presenting cells in the skin.
      One factor which may in part be limiting development and use of intradermal (ID)
      administration is concern about the ease and reliability of the needle and
      syringe-based Mantoux technique. A phase I clinical study was conducted to
      evaluate two ID adapters that have been developed as injection-delivery aids to
      increase the safety, simplicity, and reliability of ID injection: a prototype
      autodisable, intradermal (ADID) adapter for autodisable (AD) syringes, and a
      marketed side-merge adapter (SMA). Thirty healthy adult volunteers each received
      six injections of 0.1 mL of sterile saline solution. Each adapter was used to
      give injections into the upper deltoid, forearm, and suprascapular regions of
      each volunteer. The needle-bevel orientation during injection was random.
      Injection performance was determined by measuring wheal size and fluid leakage.
      Wheals were similar in size for the ADID adapter (mean 9.9 +/- 0.17 mm) and SMA
      (mean 9.8 +/- 0.15 mm). In all of the injections completed with the SMA, and 98%
      of those completed with the ADID, fluid leakage was less than 10% of the intended
      injection volume. Minor skin abrasions were the only adverse events. Based on
      self-reporting of pain, injections were well tolerated (mean pain score of 2 on a
      0-10 scale). ID delivery using the SMA and ADID adapters appears safe and
      effective.

PMID- 25964170
TI  - Moderate PEGylation of the carrier protein improves the polysaccharide-specific
      immunogenicity of meningococcal group A polysaccharide conjugate vaccine.
AB  - Neisseria meningitidis can cause severe and fulminant diseases such as
      meningitis. Meningococcal capsular polysaccharide (PS) is a key virulence
      determinant that is not able to induce immunological memory. Conjugation of PS to
      a carrier protein can significantly increase the immunogenicity of PS and induce
      immunological memory. Due to the classically described carrier-induced epitopic
      suppression (CIES) mechanisms, a strong immune response against the carrier
      protein could suppress the immune response to PS after coadministration of free
      carrier protein with the conjugate vaccine. However, it was not clear whether
      suppressing or enhancing the protein-specific immunogenicity could improve the PS
      specific immunogenicity of the conjugate vaccine. Thus, moderate PEGylation,
      extensive PEGylation and oligomerization were used to regulate the immunogenicity
      of tetanus toxoid (TT) in the conjugate vaccine (PS-TT). Moderate PEGylation led
      to a 2.7-fold increase in the PS-specific IgG titers elicited by PS-TT. In
      contrast, extensive PEGylation and oligomerization of TT led to 1.4-fold and 1.6
      fold decrease in the PS-specific IgG titers elicited by PS-TT, respectively. The
      PS-specific immunogenicity of PS-TT can be increased by moderate PEGylation
      through mild suppression of the TT-specific immunogenicity. The PS-specific
      immunogenicity of PS-TT was decreased through significant suppression or
      enhancement of the TT-specific immunogenicity. Thus, our study contributes to
      understand the CIES mechanisms and improve the PS-specific immunogenicity of a
      meningococcal PS conjugate vaccine. 

PMID- 25964171
TI  - Trans-oral robotic surgery and surgeon-performed trans-oral ultrasound for
      intraoperative location and excision of an isolated retropharyngeal lymph node
      metastasis of papillary thyroid carcinoma.
AB  - BACKGROUND: Retropharyngeal metastases are uncommon but a well-known location for
      regional spread of well-differentiated thyroid carcinoma (WDTC). Surgeon
      performed, trans-oral ultrasound (SP-TO-US) and trans-oral robot-assisted
      surgical (TORS) excision represent a unique combination of technology and
      techniques in the treatment of isolated retropharyngeal thyroid metastases.
      PATIENT FINDINGS: A patient with a history of T3N1b papillary thyroid carcinoma
      (PTC) previously treated with total thyroidectomy, left central and lateral neck
      dissection, and radioactive iodine presented with progressive elevations in serum
      thyroglobulin (Tg) from baseline of 0.2 to 0.6 MUg/L. She was found to have an
      isolated 2.6 cm left retropharyngeal nodal metastasis on MRI that was confirmed
      to be PTC on fine needle aspiration biopsy. She underwent SP-TO-US for
      identification of the node in the operating room immediately prior to TORS
      excision. There were no complications. Additional radioactive iodine was
      administered. Post-treatment iodine scans revealed resolution of avid uptake in
      left retropharynx and return of Tg to 0.2 MUg/L. SUMMARY: The combination of SP
      TO-US and TORS represents a novel combination of technology and technique for
      treatment of isolated retropharyngeal metastasis in WDTC. Trans-oral ultrasound
      allows for rapid localization of the lesion in relation to the adjacent
      neurovascular structures in the parapharynx while the robot-assisted approach
      affords a safe and effective dissection through the improved visualization and
      dexterity in a small working space. Our patient had no complications and only
      short-term dysphagia that resolved after temporary diet alteration. Risks and
      long-term morbidities associated with classical approaches to the retropharynx
      including trans-cervical and trans-mandibular, particularly in a previously
      dissected field, are avoided through this trans-oral approach. CONCLUSIONS:
      Retropharyngeal metastases are a known location for regional spread of WDTC and
      are amenable to evaluation and biopsy using TO-US by both surgical and non
      surgical providers. In cases where lateral neck dissection has already been
      performed or when traditional transcervical or transmandibular approaches to the
      retropharynx represent a comparatively extensive procedure for isolated
      metastases, SP-TO-US and TORS are safe and effective combination for surgical
      management of disease.

PMID- 25964172
TI  - Allergic rhinitis in children with adenoidal hypertrophy and otitis media with
      effusion.

PMID- 25964173
TI  - Endoscopically-derived bacterial cultures in chronic rhinosinusitis: A systematic
      review.
AB  - BACKGROUND: Culture-directed antibiotic therapy represents an important component
      in the management paradigm of chronic rhinosinusitis (CRS). The objective of this
      study was to systematically review the literature to assess culture yield of the
      most common aerobic and anaerobic pathogens. METHODS: A total of 43 studies
      between 1975 and 2010 were included. RESULTS: The composite data comprised 3528
      patients with 6005 total culture specimens. The cultures were obtained in
      operating room in 33 (76.7%) and clinic in 10 (23.3%) of the studies,
      respectively. The most common site of culture was the maxillary sinus in 18
      (41.9%) of the studies. The most common assay techniques reported were swab in 19
      (44.2%) and aspirate in 12 (27.9%) studies. The most common gram positive aerobes
      reported were coagulase negative Staphylococcus and Staphylococcus aureus in 630
      (34.7%) and 481 (26.5%) of the cultures, respectively. The most common gram
      negative aerobes included Haemophilus influenzae and Pseudomonas aeruginosa in
      245 (27.0%) and 198 (21.6%) cultures, respectively. The most common anaerobes
      reported were Peptostreptococcus species in 156 (19.6%) and Bacteroides species
      in 153 (19.2%) cultures. CONCLUSION: This study provides a composite snapshot of
      the literature accrued on the microbiology of CRS. It should serve to apprise
      clinicians on the most common aerobic and anaerobic organisms in CRS patients
      when employing culture-directed antimicrobial therapy.

PMID- 25964174
TI  - The improvement of internal consistency of the Acoustic Voice Quality Index.
AB  - PURPOSE: This investigation aims to explore the improvement of the relatively new
      hoarseness severity quantification method, called Acoustic Voice Quality Index
      (AVQI), which measures the concatenation of continuous speech (CS) and sustained
      phonation (SP) segments. Earlier investigations indicated that the proportion of
      the SP is more dominant in the final AVQI result than the CS. METHOD: Sixty voice
      samples were selected with different voice pathologies and equal distribution of
      hoarseness severity ranged from normal to severe. Every voice sample varied in
      three different durations: voice duration-one (VD-1) with seventeen syllables
      text plus three seconds of SP, voice duration-two (VD-2) with customized length
      of CS plus three seconds of SP, and voice duration-three (VD-3) with a whole text
      plus three seconds SP. All voice samples were perceptually judged on overall
      voice quality by five experienced voice clinicians. AVQI's precision and
      concurrent validity were assessed in all three VDs. Finally, the internal
      consistency across all three VDs was analyzed. RESULTS: No significant
      differences were found in the perceptual evaluation of overall voice quality
      across all three VDs by acceptable rater reliability. The concurrent validity
      distinguished in all three VDs as a marked degree of correlation (i.e., ranged
      from rs=0.891 to rs=0.929) with no significant differences across all three VDs.
      The best precision was found in VD-2. Finally, the internal consistency showed in
      VD-2 a balanced out impact of the final AVQI score with no significant
      differences from both speech tasks. CONCLUSION: Although AVQI currently uses the
      speech material of VD-1, the present study demonstrated the best results in VD-2
      (i.e., precision and internal consistency). These features of VD-2 facilitate
      higher representativity and improve the validity of this objective diagnostic
      instrument.

PMID- 25964176
TI  - Anatomy of Contemporary Partial Nephrectomy: A Dissection of the Available
      Evidence.

PMID- 25964177
TI  - Interfacial force-driven pattern formation during drying of Abeta (25-35)
      fibrils.
AB  - Pattern formation during evaporation of biofluids finds significant applications
      in the biomedical field for disease identification. Abeta (25-35) is the smallest
      peptide in the amyloid peptide family that retains the toxicity of a full length
      peptide responsible for Alzheimer's disease and is chosen here as the model
      solute. Drying experiments on substrates of varying wettability exhibit unique
      drying patterns of Abeta (25-35) fibrils visualized through fluorescence
      microscopy and transmission electron microscopy. The unique pattern formations
      can be interpreted as manifestations of the changes in the self-pinning mechanism
      with changes in wettability, which in some cases resembles the well-known coffee
      ring effect. Additionally, the delicate balance between the drag and capillary
      forces has been perturbed by initiating controlled rates of evaporation and
      probing their effects on the fibril patterning. 

PMID- 25964178
TI  - Alginate based polyurethanes: A review of recent advances and perspective.
AB  - The trend of using biopolymers in combination with synthetic polymers was
      increasing rapidly from last two or three decades. Polysaccharide based
      biopolymers especially starch, cellulose, chitin, chitosan, alginate, etc. found
      extensive applications for different industrial uses, as they are biocompatible,
      biodegradable, bio-renewable resources and chiefly environment friendly. Segment
      block copolymer character of polyurethanes that endows them a broad range of
      versatility in terms of tailoring their properties was employed in conjunction
      with various natural polymers resulted in modified biomaterials. Alginate is
      biodegradable, biocompatible, bioactive, less toxic and low cost anionic
      polysaccharide, as a part of structural component of bacteria and brown algae
      (sea weed) is quite abundant in nature. It is used in combination with
      polyurethanes to form elastomers, nano-composites, hydrogels, etc. that
      especially revolutionized the food and biomedical industries. The review
      summarized the development in alginate based polyurethanes with their potential
      applications. 

PMID- 25964175
TI  - Characterization of 1577 primary prostate cancers reveals novel biological and
      clinicopathologic insights into molecular subtypes.
AB  - BACKGROUND: Prostate cancer (PCa) molecular subtypes have been defined by
      essentially mutually exclusive events, including ETS gene fusions (most commonly
      involving ERG) and SPINK1 overexpression. Clinical assessment may aid in disease
      stratification, complementing available prognostic tests. OBJECTIVE: To determine
      the analytical validity and clinicopatholgic associations of microarray-based
      molecular subtyping. DESIGN, SETTING, AND PARTICIPANTS: We analyzed Affymetrix
      GeneChip expression profiles for 1577 patients from eight radical prostatectomy
      cohorts, including 1351 cases assessed using the Decipher prognostic assay
      (GenomeDx Biosciences, San Diego, CA, USA) performed in a laboratory with
      Clinical Laboratory Improvements Amendment certification. A microarray-based (m-)
      random forest ERG classification model was trained and validated. Outlier
      expression analysis was used to predict other mutually exclusive non-ERG ETS gene
      rearrangements (ETS(+)) or SPINK1 overexpression (SPINK1(+)). OUTCOME
      MEASUREMENTS: Associations with clinical features and outcomes by multivariate
      logistic regression analysis and receiver operating curves. RESULTS AND
      LIMITATIONS: The m-ERG classifier showed 95% accuracy in an independent
      validation subset (155 samples). Across cohorts, 45% of PCas were classified as m
      ERG(+), 9% as m-ETS(+), 8% as m-SPINK1(+), and 38% as triple negative (m-ERG(-)/m
      ETS(-)/m-SPINK1(-)). Gene expression profiling supports three underlying
      molecularly defined groups: m-ERG(+), m-ETS(+), and m-SPINK1(+)/triple negative.
      On multivariate analysis, m-ERG(+) tumors were associated with lower preoperative
      serum prostate-specific antigen and Gleason scores, but greater extraprostatic
      extension (p<0.001). m-ETS(+) tumors were associated with seminal vesicle
      invasion (p=0.01), while m-SPINK1(+)/triple negative tumors had higher Gleason
      scores and were more frequent in Black/African American patients (p<0.001).
      Clinical outcomes were not significantly different among subtypes. CONCLUSIONS: A
      clinically available prognostic test (Decipher) can also assess PCa molecular
      subtypes, obviating the need for additional testing. Clinicopathologic
      differences were found among subtypes based on global expression patterns.
      PATIENT SUMMARY: Molecular subtyping of prostate cancer can be achieved using
      extra data generated from a clinical-grade, genome-wide expression-profiling
      prognostic assay (Decipher). Transcriptomic and clinical analysis support three
      distinct molecular subtypes: (1) m-ERG(+), (2) m-ETS(+), and (3) m
      SPINK1(+)/triple negative (m-ERG(-)/m-ETS(-)/m-SPINK1(-)). Incorporation of
      subtyping into a clinically available assay may facilitate additional
      applications beyond routine prognosis.

PMID- 25964179
TI  - Antibacterial carboxymethyl cellulose/Ag nanocomposite hydrogels cross-linked
      with layered double hydroxides.
AB  - This paper deals with the preparation of antibacterial nanocomposite hydrogels
      through the combination of carboxy methyl cellulose (CMC), layered double
      hydroxides (LDH), and silver nanoparticles (AgNPs). CMC-LDH hydrogels were
      prepared by intercalating CMC into different LDHs. Then, Ag/CMC-LDH nanocomposite
      hydrogels were prepared through in situ formation of AgNPs within the CMC-LDHs.
      XRD analysis confirmed the intercalating CMC into the LDH sheets and formation of
      intercalated structures, as well as formation of AgNPs within the CMC-LDHs. SEM
      and TEM micrographs indicated well distribution of AgNPs within the Ag/CMC-LDHs.
      The prepared hydrogels showed a pH sensitive swelling behavior. The Ag/CMC-LDH
      nanocomposite hydrogels have rather higher swelling in different aqueous
      solutions in comparison with CMC-LDHs. The antibacterial activity of CMC-LDHs
      increased considerably after formation of AgNPs and was stable for more than one
      month. 

PMID- 25964180
TI  - Antiplatelet and antithrombotic activity of a fibrin(ogen)olytic protease from
      Bacillus cereus strain FF01.
AB  - Fibrin(ogen)olytic enzymes offer great promise for the treatment of thrombosis
      associated disorders. The present study describes the characterization of an
      extracellular fibrin(ogen)olytic serine protease (named Bacethrombase) purified
      from the Bacillus cereus strain FF01. The molecular mass of the Bacethrombase was
      determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis and
      matrix assisted laser desorption/ionization-time-of-flight-mass spectroscopy
      analyses at 39.5 kDa and 38,450.51 Da, respectively. The peptide mass
      fingerprinting and analyses of the composition of the amino acids revealed the
      similarity of the Bacethrombase to the bacterial serine proteases. The secondary
      structure of the Bacethrombase was composed of 14% helix, 6.6% beta-sheet, and
      79.4% random coil. Bacethrombase was found to contain 48% sialic acid and it
      preferentially degraded the Aalpha-chain of fibrinogen, as well as fibrin. The
      anticoagulant potency of the Bacethrombase was comparable with that of warfarin
      and heparin, and was corroborated by its fibrinogenolytic activity rather than
      the inhibition of thrombin, prothrombin or FXa. Bacethrombase demonstrated
      antiplatelet activity, and dose-dependently inhibited the ADP-induced platelet
      aggregation. Bacethrombase (10 mg/kg) did not show toxicity after i.v.
      administration in Wistar rats; however, it revealed an in vivo anticoagulant
      effect and significantly inhibited the carrageenan-induced in vivo thrombus
      formation in rats.

PMID- 25964181
TI  - Targeted delivery of NK007 to macrophages to treat colitis.
AB  - Macrophages are important therapeutic targets for various disorders, including
      infectious diseases, inflammatory diseases, metabolic diseases, and cancer. In
      this study, we report a novel oral delivery system for the targeted delivery of
      anti-inflammatory therapeutics to macrophages. Using this formulation, the model
      drug tylophorine malate (NK007) was tightly incorporated inside beta-glucan
      particle shells by the formation of colloidal particles with chitosan,
      tripolyphosphate, and alginate via electrostatic interactions. This formulation
      specifically delivered NK007 to macrophages in vivo after oral gavage and
      effectively cured colitis in the dextran sulfate sodium-induced murine colitis
      model, highlighting the utility of beta-glucan particles as an oral anti
      inflammation drug delivery system by targeting macrophages. In this work, NK007
      was selected as the model drug. However, this novel oral carrier system has the
      potential to be applied as a platform for the treatment of many other diseases
      for which macrophages are the therapeutic targets.

PMID- 25964182
TI  - Effects of galactose adaptation in yeast for ethanol fermentation from red
      seaweed, Gracilaria verrucosa.
AB  - A total monosaccharide concentration of 39.6 g/L, representing 74.0 % conversion
      of 53.5 g/L total carbohydrate from 80 g dw/L (8 % w/v) Gracilaria verrucosa
      slurry, was obtained by thermal acid hydrolysis and enzymatic saccharification.
      G. verrucosa hydrolysate was used as a substrate for ethanol production by
      'separate hydrolysis and fermentation' (SHF). The ethanol production and yield (Y
      EtOH) from Saccharomyces cerevisiae KCCM 1129 with and without adaptation to high
      galactose concentrations were 18.3 g/L with Y EtOH of 0.46 and 13.4 g/L with Y
      EtOH of 0.34, respectively. Relationship between galactose adaptation effects and
      mRNA transcriptional levels were evaluated with GAL gene family, regulator genes
      of the GAL genetic switch and repressor genes in non-adapted and adapted S.
      cerevisiae. The development of galactose adaptation for ethanol fermentation of
      G. verrucosa hydrolysates allowed us to enhance the overall ethanol yields and
      obtain a comprehensive understanding of the gene expression levels and metabolic
      pathways involved. 

PMID- 25964183
TI  - Efficient capturing of circulating tumor cells using a magnetic capture column
      and a size-selective filter.
AB  - Detecting and analyzing circulating tumor cells (CTCs) in the blood of cancer
      patients is a promising approach for the early diagnosis of metastasis.
      Previously, we developed a size-selective filter for capturing CTCs, but its use
      was time consuming, particularly for capturing CTCs from large volumes of blood.
      In the present study, we describe the use of a magnetic capture column for rapid
      and efficient isolation of CTCs, which were magnetically labeled with magnetite
      cationic liposomes. In the capturing process, large volumes of blood containing
      magnetically labeled cancer cells were introduced into the column at a high flow
      rate to capture the cells, which were then added into the filter at a low flow
      rate. Our results show that the combined use of the column and filter decreased
      the required time for the spiked cancer cell capture, and the recovery rate of
      the spiked cancer cells from blood was significantly higher using the combination
      process (80.7 %) than that using the filter alone (64.7 %). Moreover, almost
      twice the number of CTCs could be captured from the blood of metastatic model
      mice using the combination process. These results suggest that the developed
      process would be useful for the rapid and efficient isolation of CTCs. 

PMID- 25964184
TI  - Efficiency of EGFR mutation analysis for small microdissected cytological
      specimens using multitech DNA extraction solution.
AB  - BACKGROUND: The microdissection method has greatly facilitated the isolation of
      pure cell populations for accurate analysis of mutations. However, the absence of
      coverslips in these preparations leads to poor resolution of cellular
      morphological features. In the current study, the authors developed the MultiTech
      DNA extraction solution to improve the visualization of cell morphology for
      microdissection and tested it for the preservation of morphological properties of
      cells, quality of DNA, and ability to detect mutations. METHODS: A total of 121
      cytological samples, including fine-needle aspirates, sputum, pleural fluid, and
      bronchial washings, were selected from hospital archives. DNA extracted from
      microdissected cells was evaluated by epidermal growth factor receptor (EGFR)
      mutation analysis using pyrosequencing, Sanger sequencing, and peptide nucleic
      acid (PNA)-mediated real-time polymerase chain reaction clamping. Morphological
      features of cells as well as DNA quality and quantity were analyzed in several
      cytological samples to assess the performance of the MultiTech DNA extraction
      solution. The results were compared with previous EGFR mutation tests. RESULTS:
      The MultiTech DNA extraction solution improved the morphology of archived stained
      cells before microdissection and provided a higher DNA yield than the commercial
      QIAamp DNA Mini Kit in samples containing a minimal number of cells (25-50
      cells). The authors were able to detect identical EGFR mutations by using
      different analysis platforms and consistently identified these mutations in
      samples comprising as few as 25 microdissected cells. CONCLUSIONS: The MultiTech
      DNA extraction solution is a reliable medium that improves the resolution of cell
      morphology during microdissection. It was particularly useful in EGFR mutations
      of samples containing a small number of cells.

PMID- 25964185
TI  - Interplay between enterobactin, myeloperoxidase and lipocalin 2 regulates E. coli
      survival in the inflamed gut.
AB  - During an inflammatory response in the gut, some commensal bacteria such as E.
      coli can thrive and contribute to disease. Here we demonstrate that enterobactin
      (Ent), a catecholate siderophore released by E. coli, is a potent inhibitor of
      myeloperoxidase (MPO), a bactericidal enzyme of the host. Glycosylated Ent
      (salmochelin) and non-catecholate siderophores (yersiniabactin and ferrichrome)
      fail to inhibit MPO activity. An E. coli mutant (DeltafepA) that overproduces
      Ent, but not an Ent-deficient double mutant (DeltaaroB/DeltafepA), inhibits MPO
      activity and exhibits enhanced survival in inflamed guts. This survival advantage
      is counter-regulated by lipocalin 2, a siderophore-binding host protein, which
      rescues MPO from Ent-mediated inhibition. Spectral analysis reveals that Ent
      interferes with compound I [oxoiron, Fe(IV)=O] and reverts the enzyme back to its
      native ferric [Fe(III)] state. These findings define a fundamental mechanism by
      which E. coli surpasses the host innate immune responses during inflammatory gut
      diseases and gains a distinct survival advantage. 

PMID- 25964186
TI  - Nor-lupane triterpenoid and guaiane sesquiterpenoids from Schefflera venulosa.
AB  - A novel nor-lupane triterpenoid, 3-oxo-29alpha-hydroxy-17beta,20-epoxy-28
      norlupane (1), and two new guaiane sesquiterpenoids, schvenols A-B (2-3), has
      been isolated from leaves of Schefflera venulosa. Structures of the new compounds
      were elucidated on the basis of their spectroscopic methods, including 1D and 2D
      NMR techniques. And the structure of 1 was further confirmed by the X-ray
      diffraction analysis. None of the compounds showed inhibitory effects on NO
      release in LPS-stimulated RAW 264.7 macrophage cell line. 

PMID- 25964187
TI  - Sesquiterpenes from the fruits of Illicium jiadifengpi and their anti-hepatitis B
      virus activities.
AB  - Two new compounds, 2S-hydroxyl-jiadifenolide (1) and jiadifenlactone acid (2),
      and eight known compounds were isolated from the fruits of Illicium jiadifengpi.
      Their structures were analysed using several spectroscopic techniques, including
      1D-, 2D-NMR and HR-ESI-MS experiments. The anti-hepatitis B virus (HBV)
      activities of the isolates were evaluated via HBV transfection of the Hep G2.2.15
      cell line. The inhibitory rates of the most active compounds, compounds 4 and 5,
      on the HBeAg and HBsAg expression were 28.85+/-3.15% and 17.53+/-1.81% and
      37.93+/-2.74% and 23.47+/-9.52% at concentrations of 64.94MUM and 61.35MUM,
      respectively. 

PMID- 25964189
TI  - Combination of integrated expanded bed adsorption chromatography and
      countercurrent chromatography for the direct extraction and purification of
      pseudohypericin and hypericin from St. John's wort (Hypericum perforatum L.).
AB  - St. John's wort has attracted particular attention because of its beneficial
      effects as an antidepressant, antiviral, and anticancer agent. A method for the
      combination of integrated expanded bed adsorption chromatography and
      countercurrent chromatography for the simultaneous extraction and purification of
      pseudohypericin and hypericin from the herb is presented in this paper. Firstly,
      the constituents were extracted and directly adsorbed by expanded bed adsorption
      chromatography under optimal conditions. The stepwise elution was then performed
      by expanded bed adsorption chromatography that enriched the targets with higher
      purities and recoveries compared to other methods. Secondly, the eluent fractions
      from expanded bed adsorption chromatography were further separated by two-step
      high-speed countercurrent chromatography. A two-step high-speed countercurrent
      chromatography method with a biphasic solvent system composed of n-hexane/ethyl
      acetate/methanol/water with a volume ratio of 1:2:1:2 was performed by stepwise
      changing the flow rate of the mobile phase. Consequently, 5.6 mg of
      pseudohypericin and 2.2 mg of hypericin with purities of 95.5 and 95.0%,
      respectively, were successfully obtained from 40 mg of crude sample. 

PMID- 25964188
TI  - SC-III3, a novel scopoletin derivative, induces autophagy of human hepatoma HepG2
      cells through AMPK/mTOR signaling pathway by acting on mitochondria.
AB  - (E)-3-(4-chlorophenyl)-N-(7-hydroxy-6-methoxy-2-oxo-2H-chromen-3-yl) acrylamide
      (SC-III3), a newly synthesized derivative of scopoletin, was previously shown to
      reduce the viability of HepG2 cells and tumor growth of HepG2 xenograft mouse
      model. It induces the death of HepG2 cells by a way irrelevant to apoptosis and
      necrosis. To shed light on the cytotoxic mechanisms of SC-III3, the present study
      addresses whether and how it can induce autophagic cell death. When HepG2 cells
      were incubated with various concentrations of SC-III3, autophagic vacuoles could
      be observed by transmission electron microscopy and monodansylcadaverine
      staining. Increased expressions of LC3-II to LC3-I and Beclin-1, required for
      autophagosome formation, were accompanied. These characteristics integrally
      indicated that SC-III3 could initiate autophagy in HepG2 cells. N-acetyl-l
      cysteine (NAC), a ROS scavenger, could reverse SC-III3-caused ROS accumulation,
      but it did not affect SC-III3-induced autophagy, suggesting that ROS was not
      involved in SC-III3-mediated autophagy in HepG2 cells. SC-III3 significantly
      depressed mitochondrial function, as evidenced by disruption of mitochondrial
      transmembrane potential and loss of the mitochondrial cristae structure, as well
      as decrease of Cox-I, Cox-III, Cox-IV, and ATP levels. The autophagy and
      activation of AMPK-TSC2-mTOR-p70s6k pathways induced by SC-III3 in HepG2 cells
      could be efficiently blocked by pre-treatments of compound C (an inhibitor of
      AMPK). Moreover, addition of extracellular ATP to the cell culture media could
      reverse SC-III3-caused activation of AMPK-TSC2-mTOR-p70s6k pathway, autophagy and
      cell viability decrease in HepG2 cells. Collectively, SC-III3 leads to autophagy
      through inducing mitochondrial dysfunction, depleting ATP, and activating AMPK
      mTOR pathway, which thus reflects the cytotoxic effect of SC-III3 in HepG2 cells.

PMID- 25964190
TI  - [Improvement in the efficiency of a rehabilitation service using Lean Healthcare
      methodology].
AB  - INTRODUCTION: The aim of this study was to evaluate the reduction in costs and
      the increase in time devoted to the patient, by applying Lean Healthcare
      methodology. MATERIAL AND METHODS: A multidisciplinary team was formed, setting
      up three potential areas for improvement by performing a diagnostic process,
      including the storage and standardization of materials, and professional tasks in
      the therapeutic areas, by implementing three Lean tools: kanban, 5S and 2P.
      RESULTS: Stored material costs decreased by 43%, the cost of consumables per
      patient treated by 19%, and time dedicated to patient treatment increased by 7%.
      CONCLUSIONS: The processes were standardized and "muda" (wastefulness) was
      eliminated, thus reducing costs and increasing the value to the patient. All this
      demonstrates that it is possible to apply tools of industrial origin to the
      health sector, with the aim of improving the quality of care and achieve maximum
      efficiency.

PMID- 25964191
TI  - Development and validation of a tool incorporating quantitative fetal fibronectin
      to predict spontaneous preterm birth in symptomatic women.
AB  - OBJECTIVE: To develop a reliable and validated tool for prediction of spontaneous
      preterm birth (sPTB) in symptomatic women that incorporates quantitative
      measurements of fetal fibronectin (qfFN) and other relevant risk factors.
      METHODS: Data were analyzed that had been collected prospectively from 382 women
      who presented at an emergency assessment unit between 22 + 0 and 35 + 6 weeks'
      gestation with symptoms of preterm labor. Clinicians were blinded to qfFN
      although they were aware of qualitative fFN results. Parametric survival models
      for sPTB, with time-updated covariates, were developed for combinations of
      predictors and the best was selected using the Akaike and Bayesian information
      criteria. The model was developed on the first 190 consecutive women and
      validated on the subsequent 192. The estimated probability of delivery before 30,
      34 or 37 weeks' gestation and within 2 or 4 weeks of testing was calculated for
      each patient and was compared to actual event rates. Predictive statistics were
      calculated to compare training and validation sets. RESULTS: The final model that
      was selected used qfFN and previous sPTB/preterm prelabor rupture of membranes
      (PPROM) as predictors. Predictive statistics were similar for training and
      validation sets and there was good agreement between expected and observed sPTB
      for all outcomes. Areas under the receiver-operating characteristics curves
      ranged from 0.77 to 0.88, indicating accurate prediction across all five delivery
      outcomes. CONCLUSIONS: sPTB in symptomatic women can be predicted accurately
      using a model combining qfFN and previous sPTB/PPROM. Clinicians can use this
      model, which has been incorporated into an App (QUiPP), to determine accurately a
      woman's risk of sPTB and potentially tailor management decisions appropriately.

PMID- 25964192
TI  - Comments on ethical reporting and interpretations of findings in Hsu, Rosenthal,
      and Bailey's (2014) "the psychometric structure of items assessing
      autogynephilia".

PMID- 25964193
TI  - Characterization of electroosmotic flow through nanoporous self-assembled arrays.
AB  - Characterization of EOF mobility for Tris and TBE buffer solutions is performed
      in nanoporous arrays using the fluorescent marker method to examine the magnitude
      of EOFs through nanopores with mean diameters close to electric double layer
      thickness (Debye length). Structures made from solid silica nanospheres with
      effective pore sizes from 104 nm down to 8 nm are produced within the
      microchannel using an evaporation self-assembly method. EOF results in nanoporous
      matrices show higher EOF mobilities for stronger electrolyte solutions, which are
      drastically different compared to microchannel EOF. The effects of scaling are
      also examined by comparing the EOF mobility for varying ratios of pore diameters
      to the Debye length, which shows a surprising consistency across all particle
      sizes examined. This work demonstrates various factors which must be considered
      when designing nanofluidic devices, and discusses the causes of these small scale
      effects. 

PMID- 25964194
TI  - Occult hepatitis B virus infection among people with a family history of chronic
      hepatitis B virus infection.
AB  - The prevalence of occult hepatitis B virus infection (OBI) among people with a
      family history of chronic hepatitis B virus (HBV) infection is unclear. Serum
      samples were collected from 747 hepatitis B surface antigen (HBsAg)-negative
      people with a family history of HBV infection and 579 HBsAg-negative volunteer
      blood donors. The presence of HBV DNA was evaluated using nested PCR with primers
      specific for the X, S, and C regions of HBV. The Pre-S1/Pre-S2/ S region PCR
      products for the OBI group and their family members with chronic HBV infection
      (control group) were sequenced and compared. The prevalence of OBI was 8.0%
      (60/747) among HBsAg-negative people with a family history of chronic HBV
      infection, compared to 2.6% (15/579) among the blood donors (P < 0.05). The
      prevalence of HBV genotype B infection was lower in the OBI group than in the
      control group (P = 0.031). The substitution rates in the major hydrophilic region
      and the "a" determinant seemed to be higher in the OBI group (0.893 vs. 0.507;
      1.042 vs. 0.403, respectively), and stop codon mutations more frequent in the OBI
      sequences (OBI: 2/26, 7.7% vs. CONTROL: 0/31, 0%). However, none of these
      differences was statistically significant (P = 0.237, 0.199, 0.201,
      respectively). In summary, the prevalence of OBI among HBsAg-negative people with
      a family history of chronic HBV infection was significantly higher than that in
      Chinese blood donors. However, S region mutations and the escape mechanism are
      not likely to be the major causes of increased prevalence of OBI.

PMID- 25964195
TI  - Optimization of the Dutch matrix test by random selection of sentences from a
      preselected subset.
AB  - Matrix tests are available for speech recognition testing in many languages. For
      an accurate measurement, a steep psychometric function of the speech materials is
      required. For existing tests, it would be beneficial if it were possible to
      further optimize the available materials by increasing the function's steepness.
      The objective is to show if the steepness of the psychometric function of an
      existing matrix test can be increased by selecting a homogeneous subset of
      recordings with the steepest sentence-based psychometric functions. We took data
      from a previous multicenter evaluation of the Dutch matrix test (45 normal
      hearing listeners). Based on half of the data set, first the sentences (140 out
      of 311) with a similar speech reception threshold and with the steepest
      psychometric function (>=9.7%/dB) were selected. Subsequently, the steepness of
      the psychometric function for this selection was calculated from the remaining
      (unused) second half of the data set. The calculation showed that the slope
      increased from 10.2%/dB to 13.7%/dB. The resulting subset did not allow the
      construction of enough balanced test lists. Therefore, the measurement procedure
      was changed to randomly select the sentences during testing. Random selection may
      interfere with a representative occurrence of phonemes. However, in our material,
      the median phonemic occurrence remained close to that of the original test. This
      finding indicates that phonemic occurrence is not a critical factor. The work
      highlights the possibility that existing speech tests might be improved by
      selecting sentences with a steep psychometric function. 

PMID- 25964196
TI  - Efficacy and safety of continent anal urinary diversion for complicated bladder
      exstrophy in children by using modified Duhamel's procedure.
AB  - BACKGROUND: A high proportion of children with bladder exstrophy will continue to
      suffer from urinary incontinence and a miserable life even after a well-performed
      staged reconstruction in specialized centers. Most of those children usually have
      a normal anal sphincter allowing construction of a neobladder from the rectum, so
      they are continent without an abdominal stoma, and do not require frequent
      catheterization, which greatly contribute to a favorable body image. OBJECTIVE:
      In this study a modified Duhamel's rectal pouch done for 19 children, with
      implication of suitable stapler adopted to construct a rectal bladder with a non
      refluxing urterorectostomy, there is a theoretical advantage in our procedure of
      avoiding a mix of urine and feces. All patients were followed for up to 6 years
      (2-8 years) for efficacy, safety, subsequent renal complications, and
      surveillance for any rectal neoplastic changes in this new diversion. STUDY
      DESIGN: Assessment of electrolytes, acid base balance, and renal function were
      carried out regularly and all data were analyzed using the SPSS 9.0.1 statistical
      package and compared using a paired t test; data were considered significant if p
      < 0.05. Proctoscopy was performed 6 monthly in the first year then annually
      thereafter, and at any time if there was any rectal bleeding. RESULTS: In this
      group of patients, follow-up revealed no neoplastic changes in the rectal
      bladder, deterioration in renal function, or major electrolytes disturbance. They
      can hold up to 400 mL (350-550 mL) of urine and all are continent during the
      daytime with an emptying frequency of 3-5 h; three patients had infrequent (4
      episodes/month) nocturnal enuresis; and four cases developed pyelonephritis
      controlled with medical treatment. CONCLUSION: The continent rectal bladder
      created by using the principles of the Duhamel pull-through is feasible, easy to
      perform, successful in the immediate short term with low complications after 6
      years of follow-up and appropriately accepted by the children and their families
      with marked improvement in quality of life regarding continence; longer-term
      follow-up is requested to rule out rectal neoplastic changes. A comparative
      review of the complications, patient's acceptance, and longer-term follow-up with
      other well-known procedures, such as Mainz II, is required.

PMID- 25964197
TI  - Laparoscopic undiversion of end ureterostomy: A novel technique.
AB  - PURPOSE: We describe a novel technique of laparoscopic undiversion and
      reimplantation of end ureterostomy in children. METHODS AND TECHNIQUE: Three
      children (mean age 2.1 y, two girls) underwent laparoscopic undiversion and
      reimplantation of unilateral end ureterostomy during early infancy for
      symptomatic primary obstructive megaureter. The procedure consisted of
      laparoscopic dismantling of stoma, mobilization and medial rerouting of ureter,
      and extravesical ureteric reimplantation. RESULTS: There were no complications
      (mean follow-up 10 months). Follow-up investigations revealed only mild residual
      hydronephrosis with no ipsilateral reflux. Cosmetic results were excellent.
      CONCLUSION: Our novel technique allows laparoscopic undiversion of ureterostomy
      to be performed with success.

PMID- 25964198
TI  - The effect of penile urethral fat graft application on urethral angiogenesis.
AB  - BACKGROUND: Autologous fat grafts are rich in adipose-derived stem cells,
      providing optimal soft-tissue replacement and significant quantities of
      angiogenic growth factor. Although fat grafts (FG) are used in several clinical
      conditions, the use of FG in urethral repairs and the effects of FG to urethral
      repairs have not yet been reported. OBJECTIVE: An experimental study was
      performed to evaluate the effect of FG on urethral angiogenesis and tissue growth
      factor (GF) levels. STUDY DESIGN: Sixteen Wistar albino, adult, male rats were
      allocated into two groups: the control group (CG) (n = 8) and the experiment
      group (EG) (n = 8). After anesthetization of all rats, 3-mm vertical incisions
      were made on the urethras, and then sutured with interrupted 5/0 vicryl sutures.
      The operations were performed under a stereo dissecting microscope under
      magnification (*20). In the CG, no additional procedure was performed. In the EG
      after the same surgical procedure, 1 mm(3) FG was removed from the inguinal
      region by sharp dissection with a knife. The grafts were trimmed to 1 * 1 mm
      dimensions on millimeter paper. The FGs were placed on the repaired urethras. The
      skin was then closed. Samples from urethral and penile skin were taken 21 days
      after surgery in both groups. Density and intensity of staining with vascular
      endothelial GF (VEGF), VEGF-receptor, and endothelial-GF receptor (EGFR) in the
      endothelial and mesenchymal cells of the penile urethral vessels were
      immunohistochemically evaluated. Data obtained from immunohistochemical
      evaluations were analyzed with SPSS 15.0. The P-values lower than 0.05 were
      considered as significant. RESULTS: Density of VEGF staining was significantly
      decreased in the vascular endothelium of the EG compared to the CG (P < 0.05).
      Density of the EGFR staining was significantly decreased in the vascular
      endothelium of the EG compared to the CG (P < 0.05) (Table). Intensity of VEGF,
      VEGF-R and EGFR staining was not significantly different between the two groups.
      There were no significant differences between groups regarding to VEGFR staining
      and mesenchymal examination. DISCUSSION: Decreased density was found in the VEGF
      staining in the vascular endothelium. This could be explained by the day that the
      tissues were harvested or because autologous fat grafts might cause decreased
      growth factor levels, which is contrary to the literature data. CONCLUSION: Fat
      grafting has an immunohistochemical effect on the growth factor levels that are
      related to angiogenesis after urethral repair. It is difficult to make a firm
      conclusion about the role of fat grafting on urethral healing. Therefore, future
      studies are needed to see if FG can be used as an alternative to other procedures
      in order to avoid complications.

PMID- 25964199
TI  - Ultra-mini-percutaneous nephrolithotomy in pediatric nephrolithiasis: both low
      pressure and high efficiency.
AB  - INTRODUCTION: The management of urolithiasis in children differs from adults
      because of anatomic and metabolic abnormalities. At present, various minimally
      invasive and invasive treatment strategies have been recommended to treat urinary
      tract Stones, including shock wave lithotripsy (SWL), standard percutaneous
      nephrolithotomy (PNL), mini-PNL, retrograde intrarenal surgery (RIRS), micro-PNL,
      and a new technique termed ultra-mini PNL (UMP). UMP is a new method for the
      treatment of kidney stones. The main difference between UMP and standard PNL or
      mini-PNL lies in the small access sheath and in its design. A 9.5F pediatric
      compact cystoscope was used (Figure). A major advantage of UMP is that it
      provides similar stone-free rates when compared with standard PNL, with lower
      intrarenal pressure than micro-PNL. OBJECTIVE: The aim of the study was to
      determine the applicability and safety of UMP in the treatment of pediatric
      kidney stones. PATIENTS AND METHODS: We retrospectively reviewed the files of 39
      kidney stones in children who had undergone UMP between May 2011 and October
      2014. The indications for UMP included stones resistant to SWL, stones requiring
      repeated sessions of SWL, and stones size larger than 20 mm. RESULTS: The study
      included 17 females and 22 males, with a mean age of 5.8 +/- 4.6 years. The mean
      hemoglobin loss was 0.9 +/- 0.6 mg/dL and none of the patients required a blood
      transfusion. The complication rate of the PNL procedure was 15.3% (n = 6).
      Complete clearance was achieved in 32 patients (82%) with UMP monotherapy, which
      increased to 34% (87.1%) 4 weeks after the operation. DISCUSSION: Management of
      urolithiasis necessitates a balance between stone clearance and morbidity related
      to the procedure. SWL often leads to persistent residual stones. The developing
      RIRS can minimize the risks associated with bleeding and visceral injury, but
      sometimes the abnormal pelvicaliceal anatomy and poor imaging of the flexible
      ureteroscopy may impact its success rate and applications. It has been reported
      that PNL can be performed safely and effectively to achieve a higher stone-free
      rate; however, it has serious complications such as bleeding that requires blood
      transfusion in 11-14% of the cases with increased risk of kidney loss. The recent
      development of smaller sheaths allows tract formation with minimal damage to the
      renal parenchyma, thereby reducing procedure-related morbidity without
      diminishing its therapeutic efficacy. CONCLUSION: The most important advantage of
      this surgical technique that has been developed is similar stone-free rates to
      standard PNL and lower intrarenal pressure than micro-PNL. Our experience
      supports that UMP is safe and effective for the management of renal stones in
      children.

PMID- 25964200
TI  - Safety and efficacy of resistance exercise in prostate cancer patients with bone
      metastases.

PMID- 25964201
TI  - An Oral Formulation of YK-4-279: Preclinical Efficacy and Acquired Resistance
      Patterns in Ewing Sarcoma.
AB  - Ewing sarcoma is a transcription factor-mediated pediatric bone tumor caused by a
      chromosomal translocation of the EWSR1 gene and one of several genes in the ETS
      family of transcription factors, typically FLI1 or ERG. Full activity of the
      resulting oncogenic fusion protein occurs only after binding RNA helicase A
      (RHA), and novel biologically targeted small molecules designed to interfere with
      that interaction have shown early promise in the preclinical setting. Herein, we
      demonstrate marked preclinical antineoplastic activity of an orally bioavailable
      formulation of YK-4-279 and identify mechanisms of acquired chemotherapy
      resistance that may be exploited to induce collateral sensitivity. Daily enteral
      administration of YK-4-279 led to significant delay in Ewing sarcoma tumor growth
      within a murine model. In advance of anticipated early-phase human clinical
      trials, we investigated both de novo and acquired mechanism(s) by which Ewing
      sarcoma cells evade YK-4-279-mediated cell death. Drug-resistant clones, formed
      by chronic in vitro exposure to steadily increased levels of YK-4-279,
      overexpressed c-Kit, cyclin D1, pStat3(Y705), and PKC isoforms. Interestingly,
      cross-resistance to imatinib and enzastaurin (selective inhibitors of c-Kit and
      PKC-beta, respectively), was observed and the use of YK-4-279 with enzastaurin in
      vitro led to marked drug synergy, suggesting a potential role for combination
      therapies in the future. By advancing an oral formulation of YK-4-279 and
      identifying prominent mechanisms of resistance, this preclinical research takes
      us one step closer to a shared goal of curing adolescents and young adults
      afflicted by Ewing sarcoma.

PMID- 25964202
TI  - Cosilencing of PKM-2 and MDR-1 Sensitizes Multidrug-Resistant Ovarian Cancer
      Cells to Paclitaxel in a Murine Model of Ovarian Cancer.
AB  - Tumor multidrug resistance (MDR) is a serious clinical challenge that
      significantly limits the effectiveness of cytotoxic chemotherapy. As such,
      complementary therapeutic strategies are being explored to prevent relapse. The
      altered metabolic state of cancer cells, which perform aerobic glycolysis,
      represents an interesting target that can enable discrimination between healthy
      cells and cancer cells. We hypothesized that cosilencing of genes responsible for
      aerobic glycolysis and for MDR would have synergistic antitumor effect. In this
      study, siRNA duplexes against pyruvate kinase M2 and multidrug resistance gene-1
      were encapsulated in hyaluronic acid-based self-assembling nanoparticles. The
      particles were characterized for morphology, size, charge, encapsulation
      efficiency, and transfection efficiency. In vivo studies included biodistribution
      assessment, gene knockdown confirmation, therapeutic efficacy, and safety
      analysis. The benefit of active targeting of cancer cells was confirmed by
      modifying the particles' surface with a peptide targeted to epidermal growth
      factor receptor, which is overexpressed on the membranes of the SKOV-3 cancer
      cells. To augment the studies involving transplantation of a paclitaxel-resistant
      cell line, an in vivo paclitaxel resistance model was developed by injecting
      repeated doses of paclitaxel following tumor inoculation. The nanoparticles
      accumulated significantly in the tumors, hindering tumor volume doubling time (P
      < 0.05) upon combination therapy in both the wild-type (2-fold) and resistant (8
      fold) xenograft models. Although previous studies indicated that silencing of MDR
      1 alone sensitized MDR ovarian cancer to paclitaxel only modestly, these data
      suggest that concurrent silencing of PKM-2 improves the efficacy of paclitaxel
      against MDR ovarian cancer.

PMID- 25964203
TI  - Editorial overview: Antigen processing and presentation: Where cellular immunity
      begins.

PMID- 25964204
TI  - Synthesis of novel triplets with a 1,3,5-trioxazatriquinane skeleton and their
      pharmacologies for opioid receptors.
AB  - We designed and synthesized novel triplet molecules with 1,3,5-trioxazatriquinane
      skeletons. One class comprises double-capped triplets with a morphinan skeleton;
      the other class comprises simple phenol derivatives with phenethylamine moieties.
      One compound with m-phenolic hydroxyl group, called SYK-146, is a highly
      selective, potent agonist for the kappa receptor, with activity nearly equivalent
      to that of U-50488H. The o-phenolic isomer of SYK-146, called SYK-524, showed
      potent but non-selective agonistic activity for the opioid receptors. We also
      added several simple phenol derivatives to a library of compounds that target
      opioid receptors, and they showed high hit rates for the receptor. This library
      might also be expected to show high hit rates for other receptors. 

PMID- 25964205
TI  - Regenerative Therapy Prevents Heart Failure Progression in Dyssynchronous
      Nonischemic Narrow QRS Cardiomyopathy.
AB  - BACKGROUND: Cardiac resynchronization therapy using bi-ventricular pacing is
      proven effective in the management of heart failure (HF) with a wide QRS-complex.
      In the absence of QRS prolongation, however, device-based resynchronization is
      reported unsuitable. As an alternative, the present study tests a regenerative
      cell-based approach in the setting of narrow QRS-complex HF. METHODS AND RESULTS:
      Progressive cardiac dyssynchrony was provoked in a chronic transgenic model of
      stress-triggered dilated cardiomyopathy. In contrast to rampant end-stage disease
      afflicting untreated cohorts, stem cell intervention early in disease,
      characterized by mechanical dyssynchrony and a narrow QRS-complex, aborted
      progressive dyssynchronous HF and prevented QRS widening. Stem cell-treated
      hearts acquired coordinated ventricular contraction and relaxation supporting
      systolic and diastolic performance. Rescue of contractile dynamics was
      underpinned by a halted left ventricular dilatation, limited hypertrophy, and
      reduced fibrosis. Reverse remodeling reflected a restored cardiomyopathic
      proteome, enforced at systems level through correction of the pathological
      molecular landscape and nullified adverse cardiac outcomes. Cell therapy of a
      dyssynchrony-prone cardiomyopathic cohort translated prospectively into improved
      exercise capacity and prolonged survivorship. CONCLUSIONS: In narrow QRS HF, a
      regenerative approach demonstrated functional and structural benefit, introducing
      the prospect of device-autonomous resynchronization therapy for refractory
      disease.

PMID- 25964206
TI  - Systematic Validation of RNF213 Coding Variants in Japanese Patients With
      Moyamoya Disease.
AB  - BACKGROUND: A founder variant of RNF213, p.R4810K (c.14429G>A, rs112735431), was
      recently identified as a major genetic risk factor for moyamoya disease (MMD) in
      Japan. Although the association of p.R4810K was reported to be highly significant
      and reproducible, the disease susceptibility of other RNF213 variants remains
      largely unknown. In the present study, we systematically evaluated the coding
      variants detected in Japanese patients and controls for associations with MMD.
      METHODS AND RESULTS: To detect variants of RNF213, all coding exons were
      sequenced in 27 Japanese MMD patients without p.R4810K. We also validated all
      previously reported variants in our case-control samples and tested for
      associations in combination with previous Japanese study cohorts, including the
      1000 Genomes Project data set, as population-based controls. Forty-six missense
      variants other than p.R4810K were identified among 370 combined patients and 279
      combined controls in Japan. Sixteen of 46 variants were polymorphisms with minor
      allele frequency >1%, and, after conditioning on the p.R4810K genotype, were not
      associated with MMD. We conducted a variable threshold test using Combined
      Annotation-Dependent Depletion on the remaining 30 rare variants (minor allele
      frequency <1%), and the results showed that the frequency of potentially
      functional variants was significantly higher in patients than in controls
      (permutation, minimum P=0.045). CONCLUSIONS: Not only p.4810K but also other
      functional missense variants of RNF213 conferred susceptibility to MMD. Our
      analysis also revealed that ~20% of Japanese MMD patients did not harbor
      susceptibility variants of RNF213, indicating the presence of other
      susceptibility genes for MMD.

PMID- 25964207
TI  - Effects of parental smoking on exercise systolic blood pressure in adolescents.
AB  - BACKGROUND: In adults, exercise blood pressure seems to be more closely related
      to cardiovascular risk than resting blood pressure; however, few data are
      available on the effects of familial risk factors, including smoking habits, on
      exercise blood pressure in adolescents. METHODS AND RESULTS: Blood pressure at
      rest and during exercise, parental smoking, and other familial risk factors were
      investigated in 532 adolescents aged 12 to 17 years (14.6+/-1.5 years) in the
      Kiel EX.PRESS. (EXercise PRESSure) Study. Exercise blood pressure was determined
      at 1.5 W/kg body weight using a standardized submaximal cycle ergometer test.
      Mean resting blood pressure was 113.1+/-12.8/57.2+/-7.1 mm Hg, and exercise blood
      pressure was 149.9+/-19.8/54.2+/-8.6 mm Hg. Parental smoking increased exercise
      systolic blood pressure (+4.0 mm Hg, 3.1 to 4.9; P=0.03) but not resting blood
      pressure of the subjects (adjusted for age, sex, height, body mass index
      percentile, fitness). Parental overweight and familial hypertension were related
      to both higher resting and exercise systolic blood pressure values, whereas
      associations with an inactive lifestyle and a low educational level of the
      parents were found only with adolescents' blood pressure during exercise. The
      cumulative effect of familial risk factors on exercise systolic blood pressure
      was more pronounced than on blood pressure at rest. CONCLUSIONS: Parental smoking
      might be a novel risk factor for higher blood pressure, especially during
      exercise. In addition, systolic blood pressure during a submaximal exercise test
      was more closely associated with familial risk factors than was resting blood
      pressure, even in adolescents.

PMID- 25964208
TI  - Prehospital oral chlorhexidine does not reduce the rate of ventilator-associated
      pneumonia among critically ill trauma patients: A prospective concurrent-control
      study.
AB  - PURPOSE: The purpose of the study was to test the hypothesis that prehospital
      oral chlorhexidine administered to intubated trauma patients will decrease the
      Clinical Pulmonary Infection Score (CPIS) during the first 2 days of
      hospitalization. MATERIALS AND METHODS: Prospective interventional concurrent
      control study of all intubated adult trauma patients transported by air ambulance
      to a 711-bed Midwestern academic trauma center over a 1-year period. Patients
      transported by 2 university-based helicopters were treated with oral
      chlorhexidine after intubation, and the control group was patients transported by
      other air transport services. RESULTS: Sixty-seven patients were enrolled, of
      which 23 received chlorhexidine (9 patients allocated to the intervention were
      not treated). The change in CPIS score was no different between the intervention
      and control groups by intention to treat (1.06- vs 1.40-point reduction, P =
      .520), and no difference was observed in tracheal colonization (29.0% vs 36.7%, P
      = .586). No differences were observed in the rate of clinical pneumonia (8.7% vs
      8.6%, P = .987) or mortality (P = .196) in the per-protocol chlorhexidine group.
      CONCLUSIONS: The prehospital administration of oral chlorhexidine does not reduce
      the CPIS score over the first 48 hours of admission for intubated trauma
      patients. Further study should explore other prehospital strategies of reducing
      complications of critical illness.

PMID- 25964210
TI  - Maximum height and minimum time vertical jumping.
AB  - The performance criterion in maximum vertical jumping has typically been assumed
      to simply raise the center of mass as high as possible. In many sporting
      activities minimizing movement time during the jump is likely also critical to
      successful performance. The purpose of this study was to examine maximum height
      jumps performed while minimizing jump time. A direct dynamics model was used to
      examine squat jump performance, with dual performance criteria: maximize jump
      height and minimize jump time. The muscle model had activation dynamics, force
      length, force-velocity properties, and a series of elastic component representing
      the tendon. The simulations were run in two modes. In Mode 1 the model was placed
      in a fixed initial position. In Mode 2 the simulation model selected the initial
      squat configuration as well as the sequence of muscle activations. The inclusion
      of time as a factor in Mode 1 simulations resulted in a small decrease in jump
      height and moderate time savings. The improvement in time was mostly accomplished
      by taking off from a less extended position. In Mode 2 simulations, more
      substantial time savings could be achieved by beginning the jump in a more
      upright posture. However, when time was weighted more heavily in these
      simulations, there was a more substantial reduction in jump height. Future work
      is needed to examine the implications for countermovement jumping and to examine
      the possibility of minimizing movement time as part of the control scheme even
      when the task is to jump maximally. 

PMID- 25964211
TI  - In vivo recruitment patterns in the anterior oblique and dorsoradial ligaments of
      the first carpometacarpal joint.
AB  - The anterior oblique ligament (AOL) and the dorsoradial ligament (DRL) are both
      regarded as mechanical stabilizers of the thumb carpometacarpal (CMC) joint,
      which in older women is often affected by osteoarthritis. Inferences on the
      potential relationship of these ligaments to joint pathomechanics are based on
      clinical experience and studies of cadaveric tissue, but their functions has been
      studied sparsely in vivo. The purpose of this study was to gain insight into the
      functions of the AOL and DRL using in vivo joint kinematics data. The thumbs of
      44 healthy subjects were imaged with a clinical computed tomography scanner in
      functional-task and thumb range-of-motion positions. The origins and insertion
      sites of the AOL and the DRL were identified on the three-dimensional bone models
      and each ligament was modeled as a set of three fibers whose lengths were the
      minimum distances between insertion sites. Ligament recruitment, which
      represented ligament length as a percentage of the maximum length across the
      scanned positions, was computed for each position and related to joint posture.
      Mean AOL recruitment was lower than 91% across the CMC range of motion, whereas
      mean DRL recruitment was generally higher than 91% in abduction and flexion.
      Under the assumption that ligaments do not strain by more than 10%
      physiologically, our findings of mean ligament recruitments across the CMC range
      of motion indicate that the AOL is likely slack during most physiological
      positions, whereas the DRL may be taut and therefore support the joint in
      positions of CMC joint abduction and flexion. 

PMID- 25964209
TI  - Tamoxifen regulation of sphingolipid metabolism--Therapeutic implications.
AB  - Tamoxifen, a triphenylethylene antiestrogen and one of the first-line endocrine
      therapies used to treat estrogen receptor-positive breast cancer, has a number of
      interesting, off-target effects, and among these is the inhibition of
      sphingolipid metabolism. More specifically, tamoxifen inhibits ceramide
      glycosylation, and enzymatic step that can adventitiously support the influential
      tumor-suppressor properties of ceramide, the aliphatic backbone of sphingolipids.
      Additionally, tamoxifen and metabolites N-desmethyltamoxifen and 4
      hydroxytamoxifen, have been shown to inhibit ceramide hydrolysis by the enzyme
      acid ceramidase. This particular intervention slows ceramide destruction and
      thereby depresses formation of sphingosine 1-phosphate, a mitogenic sphingolipid
      with cancer growth-promoting properties. As ceramide-centric therapies are
      becoming appealing clinical interventions in the treatment of cancer, agents like
      tamoxifen that can retard the generation of mitogenic sphingolipids and buffer
      ceramide clearance via inhibition of glycosylation, take on new importance. In
      this review, we present an abridged, lay introduction to sphingolipid metabolism,
      briefly chronicle tamoxifen's history in the clinic, examine studies that
      demonstrate the impact of triphenylethylenes on sphingolipid metabolism in cancer
      cells, and canvass works relevant to the use of tamoxifen as adjuvant to drive
      ceramide-centric therapies in cancer treatment. The objective is to inform the
      readership of what could be a novel, off-label indication of tamoxifen and
      structurally-related triphenylethylenes, an indication divorced from estrogen
      receptor status and one with application in drug resistance. 

PMID- 25964212
TI  - A comparison of three dispersion media on the physicochemical and toxicological
      behavior of TiO2 and NiO nanoparticles.
AB  - Nanomaterials represent a burgeoning field of technological innovation. With the
      onset of environmental release and commercial product exposure associated with
      nanomaterial manufacture and proliferation, the concomitant effects on human
      health remain unknown and demand further investigation. Agglomeration of
      nanomaterials in biologically relevant media used in in vitro methods further
      complicates dosing in toxicological study. OBJECTIVE: to compare the effects of
      in vitro dispersion techniques on the physicochemical and toxicological dosimetry
      of TiO2 (<50 nm) and NiO (<20 nm) nanoparticles and some resulting toxicological
      endpoints to test for potential effects. METHODS: three media were prepared for
      A549 and 16hbe14o cells with varying concentrations of TiO2 and NiO
      nanoparticles. Physicochemical effects were analyzed with dynamic light
      scattering, ICP-MS, SEM, and TEM. Toxicological effects were determined after
      stimulation of cells with nanoparticles for 4 and 24h followed by analysis of
      inflammatory and oxidative stress markers with ELISA and RT-PCR. Our data show
      that dispersion media differentially affect physicochemical properties and
      toxicological endpoints. Therefore, we conclude that in vitro nanotoxicology
      models that use re-suspension methods of exposure yield inconsistent and
      misleading biological results due to physicochemical variation of particle
      characteristics and transport processes.

PMID- 25964213
TI  - Individuals With a Long Face Growth Pattern and Excess Inferior Scleral Exposure:
      Is There Improvement After Maxillary (Le Fort I) Advancement and Vertical
      Shortening?
AB  - PURPOSE: Excessive inferior eyelid scleral exposure is considered an unattractive
      facial feature. The purpose of this study was to identify those patients with
      long face and excess inferior scleral exposure and then assess the change after
      maxillary (Le Fort I) advancement and vertical shortening. MATERIALS AND METHODS:
      To address the research purpose, the authors executed a retrospective case series
      study. A consecutive series of patients with a long face growth pattern scheduled
      for orthognathic correction were identified. Standardized photographs were used
      to document those with excess lower eyelid scleral show. Those patients with
      excess scleral show were studied to document any change in sclera show before and
      more than 1 year after maxillary (Le Fort I) osteotomy with advancement and
      vertical shortening. The pre- and postoperative proportional values of sclera
      show were compared using the Wilcoxon signed-rank test (P < .05). Analytic model
      planning documented maxillary vector change data points as an indicator of
      maxillary deformity and the extent of horizontal advancement and vertical
      shortening to be achieved at operation. RESULTS: The study group of 10 patients
      (7 female and 3 male) with excess scleral show was derived from a larger group of
      46 patients with long face. Their ages ranged from 15 to 35 years at operation
      (mean, 23 yr). Maxillary surgical change averaged 6-mm advancement at the
      incisors (range, 4 to 10 mm), 3-mm vertical shortening at the incisors (range, 1
      to 6 mm), and 3-mm vertical shortening at the molars (range, 1 to 6 mm). Average
      decreases in scleral show of 8 and 6% compared with total eye height were noted
      in the right and left eyes, respectively. These results were statistically
      significant (P < .05). Four of the 10 patients achieved complete correction of
      inferior sclera exposure. All 10 achieved a decrease of their total eye height.
      None of the patients required or requested further cosmetic improvement in the
      zygomatico-orbital skeletal or adnexal soft tissue region. CONCLUSION: For the
      individual with a long face jaw growth pattern and pre-existing excessive lower
      eyelid sclera show, surgical correction through maxillary advancement and
      vertical shortening will create a more favorable relation among the orbits,
      ocular globes, and lower eyelids.

PMID- 25964214
TI  - Ceftriaxone ameliorates tau pathology and cognitive decline via restoration of
      glial glutamate transporter in a mouse model of Alzheimer's disease.
AB  - Glial glutamate transporter, GLT-1, is the major Na(+)-driven glutamate
      transporter to control glutamate levels in synapses and prevent glutamate-induced
      excitotoxicity implicated in neurodegenerative disorders including Alzheimer's
      disease (AD). Significant functional loss of GLT-1 has been reported to correlate
      well with synaptic degeneration and severity of cognitive impairment among AD
      patients, yet the underlying molecular mechanism and its pathological consequence
      in AD are not well understood. Here, we find the temporal decrease in GLT-1
      levels in the hippocampus of the 3xTg-AD mouse model and that the pharmacological
      upregulation of GLT-1 significantly ameliorates the age-dependent pathological
      tau accumulation, restores synaptic proteins, and rescues cognitive decline with
      minimal effects on Abeta pathology. In primary neuron and astrocyte coculture,
      naturally secreted Abeta species significantly downregulate GLT-1 steady-state
      and expression levels. Taken together, our data strongly suggest that GLT-1
      restoration is neuroprotective and Abeta-induced astrocyte dysfunction
      represented by a functional loss of GLT-1 may serve as one of the major
      pathological links between Abeta and tau pathology. 

PMID- 25964215
TI  - Hormonal programming of rat social play behavior: Standardized techniques will
      aid synthesis and translation to human health.
AB  - Early social behaviors like juvenile play are important for normal cognitive and
      social development. Deficits in these behaviors are associated with
      neurodevelopmental disorders, such as autism. Rat juvenile rough-and-tumble play
      is a useful behavioral biomarker of neurodevelopment, and is sensitive to
      chemical factors such as pre and neonatal hormones. Despite a rich body of
      literature characterizing hormonal programming of rodent juvenile play, the
      physiological mechanisms that regulate the organization of play behavior are not
      well characterized. Synthesizing results to understand the role of endocrine
      signaling in the development of play behavior remains difficult due to
      methodological inconsistency across studies. In this review, we synthesize what
      is known about hormonal mechanisms programming play, advocate standardized
      protocols for investigating rat play, and identify key areas where future
      research is needed. A synthetic understanding of the relationship between
      endocrine signaling and behavioral programming will improve our ability to
      understand the development and onset of neurodevelopmental disorders in humans
      and ultimately will help prevent these devastating conditions. 

PMID- 25964216
TI  - Molecular markers: Implications for cytopathology and specimen collection.
AB  - Cytologic specimens obtained through minimally invasive biopsy techniques are
      increasingly being used as principle diagnostic specimens for tumors arising in
      multiple sites. The number and scope of ancillary tests performed on these
      specimens have grown substantially over the past decade, including many molecular
      markers that not only can aid in formulating accurate and specific diagnoses but
      also can provide prognostic or therapeutic information to help direct clinical
      decisions. Thus, the cytopathologist needs to ensure that adequate material is
      collected and appropriately processed for the study of relevant molecular
      markers, many of which are specific to tumor site. This brief review covers
      considerations for effective cytologic specimen collection and processing to
      ensure diagnostic and testing success. In addition, a general overview is
      provided of molecular markers pertinent to tumors from a variety of sites. The
      recognition of these established and emerging molecular markers by
      cytopathologists is an important step toward realizing the promise of
      personalized medicine.

PMID- 25964217
TI  - Planctomycetes do possess a peptidoglycan cell wall.
AB  - Most bacteria contain a peptidoglycan (PG) cell wall, which is critical for
      maintenance of shape and important for cell division. In contrast, Planctomycetes
      have been proposed to produce a proteinaceous cell wall devoid of PG. The
      apparent absence of PG has been used as an argument for the putative
      planctomycetal ancestry of all bacterial lineages. Here we show, employing
      multiple bioinformatic methods, that planctomycetal genomes encode proteins
      required for PG synthesis. Furthermore, we biochemically demonstrate the presence
      of the sugar and the peptide components of PG in Planctomycetes. In addition,
      light and electron microscopic experiments reveal planctomycetal PG sacculi that
      are susceptible to lysozyme treatment. Finally, cryo-electron tomography
      demonstrates that Planctomycetes possess a typical PG cell wall and that their
      cellular architecture is thus more similar to that of other Gram-negative
      bacteria. Our findings shed new light on the cellular architecture and cell
      division of the maverick Planctomycetes. 

PMID- 25964218
TI  - Relationship of Interleukin-10 and Transforming Growth Factor-beta Levels With
      Short-Term Graft Function After Kidney Transplantation.
AB  - INTRODUCTION: We evaluated the relationship of interleukin-10 (IL-10) and
      transforming growth factor-beta (TGF-beta) levels with graft function in kidney
      transplantation patients receiving tacrolimus-based immunosuppression during the
      early post-transplantation period. MATERIAL AND METHODS: There were 112 patients
      who underwent kidney transplantation from live donors between May 2011 and May
      2013. Eight patients had at least 1 of the exclusion criteria, and the remaining
      104 patients were included in the study. The recipients underwent evaluation for
      biochemical markers, complete blood count, and creatinine and cytokine (IL-10,
      TGF-beta) levels during the pretransplantation and post-transplantation 6 months.
      RESULTS: The creatinine level was negatively correlated with IL-10 and positively
      correlated with TGF-beta levels in both the pretransplantation and early post
      transplantation period. CONCLUSION: Low serum TGF-beta and high IL-10 levels at
      post-transplantation month 6 might have a positive effect on graft survival in
      living donor kidney recipients on tacrolimus-based immunosuppressive treatment.

PMID- 25964219
TI  - Preparation of a multi-hollow magnetic molecularly imprinted polymer for the
      selective enrichment of indolebutyric acid.
AB  - A simple strategy was developed for the preparation of multi-hollow magnetic
      molecularly imprinted polymers by incorporating 3-indolebutyric acid and
      ferroferric oxide nanoparticles simultaneously into a poly(styrene-co-methacrylic
      acid) copolymer matrix. The as prepared absorbents were characterized using
      scanning electron microscopy, Fourier-transform infrared spectroscopy and mercury
      porosimetry. The adsorption isotherms of indolebutyric acid revealed that there
      are two types of affinity binding sites in the absorbents. The apparent maximum
      binding capacity and dissociation constant were 17.88 mg/g and 158.7 MUg/mL for
      high-affinity binding sites and 9.310 mg/g and 35.04 MUg/mL for low-affinity
      binding sites, respectively. The results testified that multi-hollow magnetic
      molecularly imprinted polymers possessed excellent recognition capacity and fast
      kinetic binding behavior to the objective molecules due to the high specific
      surface area as large as 511.3 m(2) /g. Recoveries of 75.5-86.8% were obtained
      for the indolebutyric acid spiked at three concentration levels in blank and pear
      samples. 

PMID- 25964220
TI  - Evaluation of a new eLearning platform for distance teaching of microsurgery.
AB  - Online learning (or eLearning) is in constant evolution in medicine. An
      analytical survey of the websites of eight academic societies and medical schools
      was carried out. These sites were evaluated against parameters that define the
      quality of an eLearning website, as well as the shareable content object
      reference model (SCORM) technical standards. All studied platforms were
      maintained by a webmaster and regularly updated. Only two platforms had
      teleconference opportunities, five had courses in PDF format, and four allowed
      online testing. Based on SCORM standards, only four platforms allowed direct
      access without a password. The content of all platforms was adaptable,
      interoperable and reusable. But their sustainability was difficult to assess. In
      parallel, we developed the first eLearning platform to be used as part of a
      university diploma in microsurgery in France. The platform was evaluated by
      students enrolled this diploma program. A satisfaction survey and platform
      evaluation showed that students were generally satisfied and had used the
      platform for microsurgery education, especially the seven students living abroad.
      ELearning for microsurgery allows the content to be continuously updated, makes
      for fewer classroom visits, provides easy remote access, and especially better
      training time management and cost savings in terms of travel and accommodations. 

PMID- 25964221
TI  - Comparison of distal interphalangeal fusion with and without joint preparation in
      cases of stage IV chondropathy.
AB  - The main complications in distal interphalangeal (DIP) fusion are non-union and
      hardware-related symptoms. The primary aim of this study was to show that joint
      preparation for DIP fusion is not necessary in cases of stage IV chondropathy.
      The secondary aim was to show that use of buried compression screws decreases the
      complication rate. This continuous retrospective study included two groups of DIP
      percutaneous arthrodesis procedures carried out with 1.8mm break-away compression
      screws: group 1 underwent joint preparation through a dorsal approach and group 2
      underwent a percutaneous procedure without joint preparation. Group 1 included 15
      patients (18 fingers) with a mean age of 65.3 years, representing nine cases of
      osteoarthritis, four cases of open trauma, one of gout, and one of rheumatoid
      arthritis. Group 2 included 18 patients (21 fingers) with a mean age of 58.9
      years, representing 16 cases of osteoarthritis, one of rheumatoid arthritis and
      one of swan-neck deformity. Tourniquet time was longer in group 1 (61min) than in
      group 2 (24min). The amount of emitted ionizing radiation was not different
      between groups. Pain and QuickDASH scores were not improved in group 1 but they
      were in group 2. There was no difference in the fusion time. One non-union was
      observed in group 1. Our results show that joint preparation for DIP arthrodesis
      is unnecessary in stage IV chondropathy. No hardware-related complications were
      observed. LEVEL OF EVIDENCE: III.

PMID- 25964222
TI  - Trends in antibiotic susceptibility of enteric fever isolates in East London.
AB  - BACKGROUND: The study sought evidence for changes in the proportions of
      antibiotic resistant strains among isolates of Salmonella enterica serovar Typhi
      (S. typhi) and Salmonella enterica serovar Paratyphi (S. paratyphi) between 2005
      and 2012. METHODS: Blood culture isolates of S. typhi and S. paratyphi from
      patients attending Newham and The Royal London Hospitals were included in the
      study. The organisms were cultured on selective media and identified by Maldi
      ToF, API 20E and serology. Minimum inhibitory concentrations (MICs) of augmentin,
      chloramphenicol, co-trimoxazole, ceftriaxone, ciprofloxacin and azithromycin were
      determined by E tests for 194 isolates. RESULTS: Median MICs of ciprofloxacin and
      ceftriaxone were stable at 0.5 mg/L and 0.125 mg/L, respectively.
      Chloramphenicol, azithromycin, co-trimoxazole and augmentin median MICs were 4
      mg/L, 8 mg/L, 0.064 mg/L and 0.5 mg/L, respectively. MIC90 values were lower than
      the resistant breakpoint for ceftriaxone, azithromycin and augmentin, but were
      >256 mg/L for chloramphenicol, 32 mg/L for co-trimoxazole and 1 mg/L for
      ciprofloxacin. CONCLUSIONS: Antibiotic resistance remained stable for enteric
      fever isolates between 2005 and 2012. The isolates remained susceptible to
      augmentin, ceftriaxone and azithromycin over this period, but the MIC90 was
      greater than the resistant breakpoint for chloramphenicol, cotrimoxazole and
      ciprofloxacin. The implications for clinical practice are that isolates of S.
      typhi and S. paratyphi from East London remain sensitive to ceftriaxone and
      azithromycin.

PMID- 25964223
TI  - PNPLA3 Gene Polymorphism Is Associated With Predisposition to and Severity of
      Alcoholic Liver Disease.
AB  - OBJECTIVES: The genetic polymorphism with an isoleucine-to-methionine
      substitution at position 148 (rs738409 C>G) in the patatin-like phospholipase
      domain protein 3 (PNPLA3) gene confers risk of steatosis. PNPLA3 polymorphism is
      shown to be associated with alcoholic liver disease (ALD). We performed a
      systematic review and meta-analysis to examine association of this genetic
      polymorphism with ALD spectrum and its severity. METHODS: Medline, Embase, and
      Cochrane Library were searched for studies on association of PNPLA3 polymorphism
      and ALD spectrum: alcoholic fatty liver (AFL), alcoholic liver injury (ALI),
      alcoholic cirrhosis (AC), and hepatocellular carcinoma (HCC). Pooled data are
      reported as odds ratio (OR) with 95% confidence interval. Heterogeneity was
      assessed using the I(2) statistics and publication bias using Egger's test and
      Begg and Mazumdar's test. Individual participant data obtained from five studies
      were used for subgroup analyses. RESULTS: Among 10 studies included in this
      pooled analysis, compared with controls, OR for rs738409 CG and GG among ALI
      patients was 1.45 (1.24-1.69) and 2.22 (1.50-3.28), respectively, compared with
      CC. Respective OR among AC patients was 2.09 (1.79-2.44) and 3.37 (2.49-4.58) and
      among AC patients with HCC was 2.87 (1.61-5.10) and 12.41 (6.99-22.03). Data for
      AFL were inconsistent. Among ALD patients, OR of CG and GG genotypes was 2.62
      (1.73-3.97) and 8.45 (2.52-28.37), respectively, for AC compared with fatty liver
      (FL) patients. Similar OR for AC compared with ALI was 1.98 (1.24-3.17) and 3.86
      (1.18-12.60). The OR for CG and GG genotypes among AC patients for HCC occurrence
      was 1.43 (0.76-2.72) and 2.81 (1.57-5.01), respectively. Individual participant
      data analysis showed age to predispose to AC among ALI patients. CONCLUSIONS:
      PNPLA3 genetic polymorphism (rs738409 C>G) is associated with increased risk for
      the entire spectrum of ALD among drinkers including ALI, AC, and HCC. Studies are
      needed to clarify association of PNPLA3 polymorphism and steatosis in alcoholics.
      PNPLA3 gene may potentially be a therapeutic target in ALD.

PMID- 25964224
TI  - Rectosigmoid Localization of Radiopaque Markers Does Not Correlate with Prolonged
      Balloon Expulsion in Chronic Constipation: Results from a Multicenter Cohort.
AB  - OBJECTIVES: Ingestion of radiopaque markers (ROMs) is a common means of assessing
      colonic transit time in chronic constipation. Because anorectal manometry (ARM)
      testing for pelvic floor dysfunction is mostly limited to academic centers,
      clinicians frequently use rectosigmoid accumulation of markers as a surrogate for
      pelvic floor dysfunction. We sought to determine whether rectosigmoid
      localization of markers on a ROM study correlated with measures of pelvic floor
      dysfunction by ARM and balloon expulsion testing. METHODS: We assembled a
      multicenter, retrospective cohort of patients diagnosed with chronic constipation
      who underwent both transit testing by ROM transit testing and ARM with balloon
      expulsion testing. We compared the proportion of patients with outlet obstruction
      by rectoanal pressure gradient or prolonged balloon expulsion stratified by
      marker location. RESULTS: There were 610 patients with both ROM testing and ARM
      with balloon expulsion testing. The mean age was 44 years and 526 were women
      (86%). Eighty-one (13%) patients had markers confined to the rectosigmoid area
      alone and were compared with 529 patients with markers elsewhere (51%) or no
      retained markers (49%). Of those with markers confined to the rectosigmoid colon,
      48 (59%) had a prolonged balloon expulsion compared with 276 (52%) who did not
      have rectosigmoid markers (P=0.28). The mean rectoanal gradient for patients with
      markers in the rectosigmoid colon was -29+/-46 mm Hg compared with -34+/-59 mm Hg
      for all others (P=0.59). CONCLUSIONS: Among patients with chronic constipation
      undergoing ROM transit testing, there is no association between rectosigmoid
      location of markers and rectoanal gradient or prolonged balloon expulsion.

PMID- 25964225
TI  - C-Reactive Protein, Fecal Calprotectin, and Stool Lactoferrin for Detection of
      Endoscopic Activity in Symptomatic Inflammatory Bowel Disease Patients: A
      Systematic Review and Meta-Analysis.
AB  - OBJECTIVES: Persistent disease activity is associated with a poor prognosis in
      inflammatory bowel disease (IBD). Therefore, monitoring of patients with intent
      to suppress subclinical inflammation has emerged as a treatment concept. As
      endoscopic monitoring is invasive and resource intensive, identification of valid
      markers of disease activity is a priority. The objective was to evaluate the
      diagnostic accuracy of C-reactive protein (CRP), fecal calprotectin (FC), and
      stool lactoferrin (SL) for assessment of endoscopically defined disease activity
      in IBD. METHODS: Databases were searched from inception to November 6, 2014 for
      relevant cohort and case-control studies that evaluated the diagnostic accuracy
      of CRP, FC, or SL and used endoscopy as a gold standard in patients with symptoms
      consistent with active IBD. Sensitivities and specificities were pooled to
      generate operating property estimates for each test using a bivariate diagnostic
      meta-analysis. RESULTS: Nineteen studies (n=2499 patients) were eligible. The
      pooled sensitivity and specificity estimates for CRP, FC, and SL were 0.49 (95%
      confidence interval (CI) 0.34-0.64) and 0.92 (95% CI 0.72-0.96), 0.88 (95% CI
      0.84-0.90) and 0.73 (95% CI 0.66-0.79), and 0.82 (95% CI 0.73-0.88) and 0.79 (95%
      CI 0.62-0.89), respectively. FC was more sensitive than CRP in both diseases and
      was more sensitive in ulcerative colitis than Crohn's disease. CONCLUSIONS:
      Although CRP, FC, and SL are useful biomarkers, their value in managing
      individual patients must be considered in specific clinical contexts.

PMID- 25964226
TI  - Anxiety and Depression Increase in a Stepwise Manner in Parallel With Multiple
      FGIDs and Symptom Severity and Frequency.
AB  - OBJECTIVES: Anxiety and depression occur frequently in patients with functional
      gastrointestinal disorders (FGIDs), but their precise prevalence is unknown. We
      addressed this issue in a large cohort of adult patients and determined the
      underlying factors. METHODS: In total, 4,217 new outpatients attending 2
      hospitals in Hamilton, Ontario, Canada completed questionnaires evaluating FGIDs
      and anxiety and depression (Hospital Anxiety and Depression scale). Chart review
      was performed in a random sample of 2,400 patients. RESULTS: Seventy-six percent
      of patients fulfilled Rome III criteria for FGIDs, but only 57% were diagnosed
      with FGIDs after excluding organic diseases, and the latter group was considered
      for the analysis. Compared with patients not meeting the criteria, prevalence of
      anxiety (odds ratio (OR) 2.66, 95% confidence interval (CI): 1.62-4.37) or
      depression (OR 2.04, 95% CI: 1.03-4.02) was increased in patients with FGIDs. The
      risk was comparable to patients with organic disease (anxiety: OR 2.12, 95% CI:
      1.24-3.61; depression: OR 2.48, 95% CI: 1.21-5.09). The lowest prevalence was
      observed in asymptomatic patients (OR 1.37; 95% CI 0.58-3.23 and 0.51; 95% CI
      0.10-2.48; for both conditions, respectively). The prevalence of anxiety and
      depression increased in a stepwise manner with the number of co-existing FGIDs
      and frequency and/or severity of gastrointestinal (GI) symptoms. Psychiatric
      comorbidity was more common in females with FGIDs compared with males (anxiety OR
      1.73; 95% CI 1.35-2.28; depression OR 1.52; 95% CI 1.04-2.21). Anxiety and
      depression were formally diagnosed by the consulting physician in only 22% and 9%
      of patients, respectively. CONCLUSIONS: Psychiatric comorbidity is common in
      patients referred to a secondary care center but is often unrecognized. The
      prevalence of both anxiety and depression is influenced by gender, presence of
      organic diseases, and FGIDs, and it increases with the number of coexistent FGIDs
      and frequency and severity of GI symptoms.

PMID- 25964227
TI  - Racial minorities are more likely than whites to report lack of provider
      recommendation for colon cancer screening.
AB  - OBJECTIVES: Although screening for colorectal cancer (CRC) is recommended for all
      adults aged 50 to 75 years in the United States, there are racial and ethnic
      disparities in who receives screening. Individuals lacking appropriate CRC
      screening cite various reasons for nonadherence, including lack of provider
      recommendation for screening. The purpose of this study is to evaluate the
      association between patient race and lack of provider recommendation for CRC
      screening as the primary reason for screening nonadherence. METHODS: We conducted
      a cross-sectional observational study of individuals aged 50 to 75 years from the
      2009 California Health Interview Survey who reported nonadherence to 2008 United
      States Preventive Service Task Force CRC screening guidelines. The outcome was
      self-report that the main reason for not undergoing CRC screening was lack of a
      physician recommendation ("non-recommendation") for screening. We performed
      logistic regression to determine significant predictors of non-recommendation,
      with particular attention to the role of race. RESULTS: The study cohort included
      5,793 unscreened subjects. Of the subjects, 19.1% reported that lack of a
      provider recommendation was the main reason for CRC nonscreening. African
      Americans (adjusted odds ratio (adj. OR) 1.46, 95% confidence interval (CI) 1.03
      2.05) and English-speaking Asians (adj. OR 1.65, 95% CI 1.24-2.20) were more
      likely than whites to report physician non-recommendation as the main reason for
      lack of screening. Asian non-English speakers, however, were less likely to
      report physician non-recommendation (adj. OR 0.31, 95% CI 0.11-0.91). CONCLUSION:
      Racial minorities are less likely than whites to receive a physician
      recommendation for CRC screening. Future research should evaluate why race
      appears to influence provider recommendations to pursue CRC screening; this is an
      important step to reduce disparities in CRC screening and lessen the burden of
      CRC in the United States.

PMID- 25964228
TI  - Dynamic reconstruction of complex abdominal wall defects with the pedicled
      innervated vastus lateralis and anterolateral thigh PIVA flap.
AB  - BACKGROUND AND AIM: Reconstruction of large and chronically infected recurrent
      abdominal wall defects with exposed bowel in a scarred wound environment, when
      component release has been previously performed but failed, is a veritable
      challenge. We use a pedicled innervated vastus lateralis muscle with a
      fasciocutaneous anterolateral thigh flap (PIVA flap) to restore the continuity of
      the abdominal wall with vascularised tissues and create a dynamic component that
      improves the functional outcome. MATERIALS AND METHODS: A one-stage PIVA flap was
      used in 15 patients with grade 4 transmural chronically infected defects. They
      had a mean of 4.53 previous laparotomies and important co-morbidities. We
      determined post-operative reconstructive abdominal wall strength using a
      validated quality-of-life (QoL) hernia-related questionnaire and modified it to
      quantify donor-site morbidity at the thigh. We measured the maximal force
      generated at 60 degrees /s and the force velocity at 120 degrees /s by isokinetic
      dynamometric analysis at 3 and 12 months. Electromyography (EMG) was performed 12
      months after the reconstruction to analyse the contractile integrity of the
      vastus lateralis segment. A two-sided sign test was used to analyse data.
      RESULTS: All transmural chronic wounds healed without recurrence. Dynamometric
      strength increased significantly in the abdominal wall musculature (p < 0.016)
      and in the donor thigh (p < 0.023) between 3 months and 12 months after the
      intervention, which reflected in the EMG outcome and the high scores in the QoL
      measurements after 12 months. CONCLUSIONS: The PIVA flap revascularises the
      scarred milieu, adds a dynamic component to improve function and may reach up to
      the xiphoid process. Donor-site morbidity is limited.

PMID- 25964229
TI  - Allosensitization following skin allografts in acute burn management: Are burns
      patients suitable face transplant candidates?

PMID- 25964230
TI  - Strategies for customized neck reconstruction based on the pre-expanded
      superficial cervical artery flap.
AB  - BACKGROUND: It is still highly challenging to restore the esthetic neck contour
      for postburn deformities. In many patients with burns, the back skin remains
      intact, which is a useful donor site for extensive contracture release. As the
      main technique, the refinement of the pre-expanded superficial cervical artery
      (SCA) flaps may improve its application in diverse neck contractures. METHODS:
      This study reviewed the cases of three types of neck contractures that were
      reconstructed with pre-expanded SCA flaps: (1) for unilateral neck contractures,
      the flaps were harvested as pedicled perforator flaps including a small amount of
      muscle; (2) for lateral and anterior neck contractures, vascular augmentation
      with circumflex scapular vessels was used to increase the flap size; (3) for
      contractures of the entire neck, maximal flap release with pedicle dissection
      toward the origin of the superficial cervical vessels allowed for reaching
      contralateral defects. RESULTS: From March 2010 to September 2012, pre-expanded
      SCA flaps were recommended in 15 patients with severe neck contracture. Tip
      necrosis occurred in one patient. The donor sites were closed primarily in all
      cases. One patient had donor-site wound dehiscence that healed within 2 weeks by
      conservative management. All patients had restored neck extension to a near
      normal position without the sense of restricted neck flexion or rotation.
      CONCLUSIONS: Pre-expanded SCA flaps are practical and flexible for the
      reconstruction of diverse scar contractures ranging from unilateral to total neck
      lesions. Considering the reconstructive efficiency and the reduced donor-site
      morbidity, this flap may be an ideal option for the reconstruction of severe neck
      scar contractures.

PMID- 25964231
TI  - Characterization of lysozyme adsorption in cellulosic chromatographic materials
      using small-angle neutron scattering.
AB  - Measurements of the nanoscale structure of chromatographic adsorbents and the
      associated distribution of sorbed protein within the media can facilitate
      improvements in such media. We demonstrate a new technique for this purpose using
      small-angle neutron scattering (SANS) to characterize the nano- to microscale
      structure of the chromatographic media and sorbed protein under conditions
      relevant for preparative chromatographic separations. The adsorption of lysozyme
      on cellulosic S HyperCelTM (Pall Corporation), a strong cation exchanger, was
      investigated by SANS. The scattering spectrum is reduced to three contributions
      arising from (1) the chromatographic medium, (2) discrete protein molecules, and
      (3) the distribution of sorbed protein within the medium. These contributions are
      quantified for a range of protein loadings. The total concentration of protein in
      the chromatographic media can be quantified from the SANS spectrum and the
      protein is observed to retain its tertiary structure upon adsorption, within the
      resolution of the method. Further analysis of the SANS spectra shows that protein
      adsorption is uniform in the media. These measurement techniques provide new and
      valuable nanoscale information about protein sorption in chromatographic media. 

PMID- 25964232
TI  - [Ventilator-associated pneumonia due to Chryseobacterium indologenes].

PMID- 25964233
TI  - Home-based urinary HPV DNA testing in women who do not attend cervical cancer
      screening clinics.
AB  - In France, cervical cancer screening is currently based on cytological
      examination of a Pap smear for women aged 25 to 65, but screening coverage is
      unsatisfactory. Previous studies have shown that self-sampling for human
      papillomavirus (HPV) testing increases rates of compliance. With this purpose in
      mind, we performed the CapU study to evaluate the acceptance of a urinary HPV
      test. Letters proposing a new cervical cancer screening method using at-home
      urine self-sampling were sent to 5000 women aged 40-65 years who had not had a
      Pap smear over the past three years. The participating patients had to send their
      urine samples to the Angers Hospital Virology Laboratory for analysis using real
      time PCR. Of the 771 samples received, 687 were analyzed. High-risk HPV were
      detected in 29 women. In follow-up, 28 women with positive urinary HPV results
      had a Pap smear or colposcopy done. The cytological results showed nine abnormal
      Pap smears, among which histology studies confirmed three cases of cervical
      intraepithelial neoplasia grade III lesions. Our study shows that urinary HPV
      testing may be pertinent to women who do not have cervical Pap smears done and
      lead to the diagnosis of high-grade cervical lesions. 

PMID- 25964234
TI  - Targeted empiric antibiotic therapy for children with non-oncological
      comorbidities and community-onset invasive bacterial infections.
AB  - OBJECTIVES: To describe the aetiology, risk factors, treatment and outcome of
      children with community-onset invasive bacterial infections (IBI) and determine
      the appropriateness of the nationally recommended empiric antibiotic therapy in
      children with non-oncological comorbidities. METHOD: The CABIN network
      prospectively collected clinical information for all positive blood and
      cerebrospinal fluid cultures in children aged 1 month to 15 years in southwest
      London over three years. RESULTS: During 2009-11, 119 healthy children each had a
      single IBI episode and 61 children with non-oncological comorbidities had 83 IBI
      episodes. The pathogens causing IBI in children with comorbidities and no central
      venous catheter (CVC) were similar to those causing IBI in healthy children.
      However, those with a CVC had multiple IBI episodes, often with pathogens usually
      associated with nosocomial infection. In particular, gastro-intestinal commensals
      were frequently responsible for IBI in TPN-dependent children with gastro
      intestinal disease (16/43 episodes) and those with liver disease (8/43).
      Nationally recommended antibiotics were commenced empirically in 93%, with
      additional or alternate antibiotics more likely to be prescribed in children with
      comorbidities or those requiring intensive care. Fifteen children died (11
      healthy, 4 with comorbidity), including 12 who died before arrival or in the
      Emergency Department. CONCLUSION: Increasing care of children with comorbidities
      in the community has resulted in a significant proportion of community-onset IBI
      occurring in this group. Children with a CVC in situ - particularly those with
      gastro-intestinal and liver disease - were infected with a wider range of
      potentially more virulent pathogens. They might benefit from more broad-spectrum
      antimicrobial cover.

PMID- 25964235
TI  - Field evaluation of targeted selective treatments to control subclinical
      gastrointestinal nematode infections on small ruminant farms.
AB  - Targeted selective treatments (TST) are designed to identify those animals that
      would actually benefit from anthelmintic treatment, thus reducing the amount of
      drugs used and bringing down economic cost. In this study we assayed three TST
      programs based on GIN egg output, clinical sign and live weight criteria in a
      single area where only sub-clinical infections tend to occur and no anthelmintic
      resistance is reported. The study was carried out from February 2011 to August
      2013 on four farms applying different management systems: an Ovine Extensive
      System, Ovine Semi-extensive Semi-irrigated System focusing on "Rubia del Molar"
      and Colmenarena" breeds, Ovine Semi-extensive System and Caprine Organic Semi
      extensive System. The number of sheep and goats treated in all the TST strategies
      was lower in comparison with systematic treatments, especially when selected
      based on clinical signs (100%, in both years), followed by egg output (87.57% and
      90.44% in the first and second year respectively) and finally by live weight
      (37.95% and 96.69%, in the first and second year respectively). FEC was low
      throughout the study for all animals and groups. Apparently, the TST applied did
      not influence live body weight. Preliminary results show that all three targeted
      selective treatments significantly reduced the number of animals treated and the
      cost of anthelmintic treatment on the farms, maintaining productivity in a low
      challenge environment. These results also seem to indicate that systematic
      anthelmintic treatments are unnecessary under these circumstances and traditional
      anthelmintic regimes should therefore be modified. 

PMID- 25964236
TI  - Experimental transmission of Cystoisospora felis-like coccidium from bobcat (Lynx
      rufus) to the domestic cat (Felis catus).
AB  - Cystoisospora felis is an ubiquitous coccidian of cats. The domestic cat (Felis
      catus) is its definitive host and several mammalian and avian species are its
      optional intermediate/transport hosts. Nothing is known if it is transmissible to
      wild felids. In the present study C. felis-like oocysts were found in two
      naturally infected bobcats (Lynx rufus) from Pennsylvania. To study transmission
      of C. felis-like parasite from bobcats to domestic cats, sporulated oocysts of C.
      felis-like from one bobcat were orally inoculated into interferon gamma gene
      knockout (KO) mice, and 56 days later tissues of KO mice were fed to two
      coccidian-free cats; two littermate cats were uninoculated controls. The
      inoculated cats and controls were euthanized five and seven days later, and their
      small intestines were studied histologically. One inoculated cat excreted C.
      felis-like oocysts seven days post inoculation (p.i.) and was immediately
      euthanized. Mature schizonts, mature male and female gamonts, and unsporulated
      oocysts were found in the lamina propria of small intestine; these stages were
      morphologically similar to C. felis of domestic cats. No parasites were seen in
      histological sections of small intestines of the remaining three cats. The
      experiment was terminated at seven days p.i. (minimum prepatent period for C.
      felis) to minimize spread of this highly infectious parasite to other cats.
      Although oocysts of the parasite in bobcats were morphologically similar to C.
      felis of domestic cats, the endogenous stages differed in their location of
      development. The bobcat derived parasite was located in the lamina propria of
      ileum whereas all endogenous stages of C. felis of domestic cats are always
      located in enterocytes of intestinal epithelium. Characterization of DNA isolated
      from C. felis-like oocysts from the donor bobcat revealed that sequences of the
      ITS1 region was only 87% similar to the ITS1 region of C. felis from domestic
      cats. These results indicate that the parasite in bobcat is likely different than
      C. felis of cats. 

PMID- 25964238
TI  - Transcranial vibro-acoustography can detect traumatic brain injury, in-vivo:
      Preliminary studies.
AB  - Vibro-acoustography (VA) uses two or more beams of confocal ultrasound to
      generate local vibrations within their target tissue through induction of a time
      dependent radiation force whose frequency equals that of the difference of the
      applied frequencies. While VA has proven effective for assaying the mechanical
      properties of clinically relevant tissue such as breast lesions and tissue
      calcifications, its application to brain remains unexplored. Here we investigate
      the ability of VA to detect acute and focal traumatic brain injury (TBI) in-vivo
      through the use of transcranially delivered high-frequency (2 MHz) diagnostic
      focused ultrasound to rat brain capable of generating measurable low-frequency
      (200-270 kHz) acoustic emissions from outside of the brain. We applied VA to
      acute sham-control and TBI model rats (sham N=6; TBI N=6) and observed that
      acoustic emissions, captured away from the site of TBI, had lower amplitudes for
      TBI as compared to sham-TBI animals. The sensitivity of VA to acute brain damage
      at frequencies currently transmittable across human skulls, as demonstrated in
      this preliminary study, supports the possibility that the VA methodology may one
      day serve as a technique for detecting TBI.

PMID- 25964239
TI  - Effect of a functionally graded soft middle layer on Love waves propagating in
      layered piezoelectric systems.
AB  - Numerical examples for wave propagation in a three-layer structure have been
      investigated for both electrically open and shorted cases. The first order
      differential equations are solved by both methods ODE and Stiffness matrix. The
      solutions are used to study the effects of thickness and gradient coefficient of
      soft middle layer on the phase velocity and on the electromechanical coupling
      factor. We demonstrate that the electromechanical coupling factor is
      substantially increased when the equivalent thickness is in the order of the
      wavelength. The effects of gradient coefficients are plotted for the first mode
      when electrical and mechanical gradient variations are applied separately and
      altogether. The obtained deviations in comparison with the ungraded homogenous
      film are plotted with respect to the dimensionless wavenumber. The impact related
      to the gradient coefficient of the soft middle layer, on the mechanical
      displacement and the Poynting vector, is carried out. The numericals results are
      illustrated by a set of appropriate curves related to various profiles. The
      obtained results set guidelines not only for the design of high-performance
      surface acoustic wave (SAW) devices, but also for the measurement of material
      properties in a functionally graded piezoelectric layered system using Love
      waves. 

PMID- 25964240
TI  - Monitoring and removal of cyanobacterial toxins from drinking water by algal
      activated carbon.
AB  - Microcystins (MCs) are the most potent toxins that can be produced by
      cyanobacteria in drinking water supplies. This study investigated the abundance
      of toxin-producing algae in 11 drinking water treatment plants (DWTPs). A total
      of 26 different algal taxa were identified in treated water, from which 12% were
      blue green, 29% were green, and 59% were diatoms. MC levels maintained strong
      positive correlations with number of cyanophycean cells in raw and treated water
      of different DWTPs. Furthermore, the efficiency of various algal-based adsorbent
      columns used for the removal of these toxins was evaluated. The MCs was adsorbed
      in the following order: mixed algal-activated carbon (AAC) >= individual AAC >
      mixed algal powder > individual algal powder. The results showed that the AAC had
      the highest efficient columns capable of removing 100% dissolved MCs from
      drinking water samples, thereby offering an economically feasible technology for
      efficient removal and recovery of MCs in DWTPs. 

PMID- 25964241
TI  - Chromium-induced skin damage among Taiwanese cement workers.
AB  - Little research has been done on the relationships between chromium exposure,
      skin barrier function, and other hygienic habits in cement workers. Our purpose
      was to investigate chromium-induced skin barrier disruption due to cement
      exposure among cement workers. One hundred and eight cement workers were
      recruited in this study. Urinary chromium concentration was used to characterize
      exposure levels. The biological exposure index was used to separate high and low
      chromium exposure. Transepidermal water loss (TEWL) was used to assess the skin
      barrier function. TEWL was significantly increased in workers with high chromium
      exposure levels than those with low chromium exposure levels (p = 0.048). A
      positive correlation was also found between urinary chromium concentration and
      TEWL (R = 0.28, p = 0.004). After adjusting for smoking status and glove use, a
      significant correlation between urinary chromium concentrations and TEWL
      remained. Moreover, workers who smoked and had a high chromium exposure had
      significantly increased TEWL compared to nonsmokers with low chromium exposure (p
      = 0.01). Skin barrier function of cement workers may have been disrupted by
      chromium in cement, and smoking might significantly enhance such skin barrier
      perturbation with chromium exposure. Decreased chromium skin exposure and smoking
      cessation should be encouraged at work. 

PMID- 25964237
TI  - Direct effects of leptin and adiponectin on peripheral reproductive tissues: a
      critical review.
AB  - Obesity is a risk factor for infertility and adverse reproductive outcomes.
      Adipose tissue is an important endocrine gland that secretes a host of endocrine
      factors, called adipokines, which modulate diverse physiologic processes
      including appetite, metabolism, cardiovascular function, immunity and
      reproduction. Altered adipokine expression in obese individuals has been
      implicated in the pathogenesis of a host of health disorders including diabetes
      and cardiovascular disease. It remains unclear whether adipokines play a
      significant role in the pathogenesis of adverse reproductive outcomes in obese
      individuals and, if so, whether the adipokines are acting directly or indirectly
      on the peripheral reproductive tissues. Many groups have demonstrated that
      receptors for the adipokines leptin and adiponectin are expressed in peripheral
      reproductive tissues and that these adipokines are likely, therefore, to exert
      direct effects on these tissues. Many groups have tested for direct effects of
      leptin and adiponectin on reproductive tissues including the testis, ovary,
      uterus, placenta and egg/embryo. The hypothesis that decreased fertility
      potential or adverse reproductive outcomes may result, at least in part, from
      defects in adipokine signaling within reproductive tissues has also been tested.
      Here, we present a critical analysis of published studies with respect to two
      adipokines, leptin and adiponectin, for which significant data have been
      generated. Our evaluation reveals significant inconsistencies and methodological
      limitations regarding the direct effects of these adipokines on peripheral
      reproductive tissues. We also observe a pervasive failure to account for in vivo
      data that challenge observations made in vitro. Overall, while leptin and
      adiponectin may directly modulate peripheral reproductive tissues, existing data
      suggest that these effects are minor and non-essential to human or mouse
      reproductive function. Current evidence suggests that direct effects of leptin or
      adiponectin on peripheral reproductive tissues are unlikely to factor
      significantly in the adverse reproductive outcomes observed in obese individuals.

PMID- 25964242
TI  - Self-Regulation of Beer Advertising: A Comparative Analysis of Perceived
      Violations by Adolescents and Experts.
AB  - AIMS: We assessed the impact of the 2010 revisions to Brazil's self-regulatory
      alcohol marketing code using expert and adolescent raters. METHODS: Five popular
      TV beer ads were selected. Ads were rated based on the 2010 Brazilian self
      regulatory marketing code. The expert group (N = 31) represented health-related
      professions; the adolescent group (N = 110) were public high school students.
      RESULTS: At least 1 ad violated 11 of 17 guidelines included in the study.
      Ratings by experts and adolescents were similar. Both found violations in all
      sections of the self-regulatory code, but significant group differences were seen
      in applying the section that prohibits the promotion of excessive alcohol
      consumption, with experts identifying more violations than adolescents.
      CONCLUSION: Beer ads in the sample systematically violated the self-regulatory
      standards for alcohol advertising in Brazil according to both experts and youth.
      Public policies for more effective restrictions and prohibitions in alcohol ads
      should be considered.

PMID- 25964243
TI  - Effects of Specific Alcohol Control Policy Measures on Alcohol-Related Mortality
      in Russia from 1998 to 2013.
AB  - AIMS: To elucidate the possible effects of alcohol control policy measures on
      alcohol-related mortality in Russia between 1998 and 2013. METHODS: Trends in
      mortality, alcohol production and sales were analyzed in conjunction with alcohol
      control legislative measures. Correlation analysis of health and alcohol market
      indicators was performed. RESULTS: Ethyl alcohol production was the strongest
      correlate of alcohol-related mortality, which is probably due to the fact that
      ethyl alcohol is used for both recorded and unrecorded alcohol production.
      Measures producing greatest mortality reduction effect included provisions which
      reduced ethyl alcohol production (introduction of minimum authorized capital for
      ethyl alcohol and liquor producers in 2006 and the requirement for distillery
      dreg processing), as well as measures to tax and denaturize ethanol-containing
      liquids in 2006. Liquor tax decrease in real terms was associated with rising
      mortality in 1998-1999, while excise tax increase was associated with mortality
      reduction in 2004 and since 2012. Conventional alcohol control measures may also
      have played a moderately positive role. CONCLUSIONS: Countries with high alcohol
      related mortality should aim for a reduction in spirits consumption as a major
      health policy. Alcohol market centralization and reduction of the number of
      producers can have immediate strong effects on mortality. These measures should
      be combined with an increase in alcohol taxes and prices, as well as other
      established alcohol policy measures. In 2015 in Russia, this is not being
      implemented. In Russia, legislation enforcement including excise tax collection
      remains the major challenge. Another challenge will be the integration into the
      Eurasian Economic Union.

PMID- 25964244
TI  - Phase I Study of Single-Agent AZD1775 (MK-1775), a Wee1 Kinase Inhibitor, in
      Patients With Refractory Solid Tumors.
AB  - PURPOSE: Wee1 tyrosine kinase phosphorylates and inactivates cyclin-dependent
      kinase (Cdk) 1/2 in response to DNA damage. AZD1775 is a first-in-class inhibitor
      of Wee1 kinase with single-agent antitumor activity in preclinical models. We
      conducted a phase I study of single-agent AZD1775 in adult patients with
      refractory solid tumors to determine its maximum-tolerated dose (MTD),
      pharmacokinetics, and modulation of phosphorylated Tyr15-Cdk (pY15-Cdk) and
      phosphorylated histone H2AX (gammaH2AX) levels in paired tumor biopsies. PATIENTS
      AND METHODS: AZD1775 was administered orally twice per day over 2.5 days per week
      for up to 2 weeks per 21-day cycle (3 + 3 design). At the MTD, paired tumor
      biopsies were obtained at baseline and after the fifth dose to determine pY15-Cdk
      and gammaH2AX levels. Six patients with BRCA-mutant solid tumors were also
      enrolled at the MTD. RESULTS: Twenty-five patients were enrolled. The MTD was
      established as 225 mg twice per day orally over 2.5 days per week for 2 weeks per
      21-day cycle. Confirmed partial responses were observed in two patients carrying
      BRCA mutations: one with head and neck cancer and one with ovarian cancer. Common
      toxicities were myelosuppression and diarrhea. Dose-limiting toxicities were
      supraventricular tachyarrhythmia and myelosuppression. Accumulation of drug (t1/2
      approximately 11 hours) was observed. Reduction in pY15-Cdk levels (two of five
      paired biopsies) and increases in gammaH2AX levels (three of five paired
      biopsies) were demonstrated. CONCLUSION: This is the first report of AZD1775
      single-agent activity in patients carrying BRCA mutations. Proof-of-mechanism was
      demonstrated by target modulation and DNA damage response in paired tumor
      biopsies.

PMID- 25964245
TI  - Course and Predictors of Cognitive Function in Patients With Prostate Cancer
      Receiving Androgen-Deprivation Therapy: A Controlled Comparison.
AB  - PURPOSE: Men receiving androgen-deprivation therapy (ADT) for prostate cancer may
      be at risk for cognitive impairment; however, evidence is mixed in the existing
      literature. Our study examined the impact of ADT on impaired cognitive
      performance and explored potential demographic and genetic predictors of impaired
      performance. PATIENTS AND METHODS: Patients with prostate cancer were assessed
      before or within 21 days of starting ADT (n = 58) and 6 and 12 months later. Age-
      and education-matched patients with prostate cancer treated with prostatectomy
      only (n = 84) and men without prostate cancer (n = 88) were assessed at similar
      intervals. Participants provided baseline blood samples for genotyping. Mean
      level cognitive performance was compared using mixed models; cognitive impairment
      was compared using generalized estimating equations. RESULTS: ADT recipients
      demonstrated higher rates of impaired cognitive performance over time relative to
      all controls (P = .01). Groups did not differ at baseline (P > .05); however, ADT
      recipients were more likely to demonstrate impaired performance within 6 and 12
      months (P for both comparisons < .05). Baseline age, cognitive reserve,
      depressive symptoms, fatigue, and hot flash interference did not moderate the
      impact of ADT on impaired cognitive performance (P for all comparisons >= .09).
      In exploratory genetic analyses, GNB3 single-nucleotide polymorphism rs1047776
      was associated with increased rates of impaired performance over time in the ADT
      group (P < .001). CONCLUSION: Men treated with ADT were more likely to
      demonstrate impaired cognitive performance within 6 months after starting ADT
      relative to matched controls and to continue to do so within 12 months after
      starting ADT. If confirmed, findings may have implications for patient education
      regarding the risks and benefits of ADT.

PMID- 25964246
TI  - Identification of a Low-Risk Luminal A Breast Cancer Cohort That May Not Benefit
      From Breast Radiotherapy.
AB  - PURPOSE: To determine the prognostic and predictive value of intrinsic subtyping
      by using immunohistochemical (IHC) biomarkers for ipsilateral breast relapse
      (IBR) in participants in an early breast cancer randomized trial of tamoxifen
      with or without breast radiotherapy (RT). PATIENTS AND METHODS: IHC analysis of
      estrogen receptor, progesterone receptor, human epidermal growth factor receptor
      2 (HER2), cytokeratin 5/6, epidermal growth factor receptor, and Ki-67 was
      conducted on 501 of 769 available blocks. Patients were classified as luminal A
      (n = 265), luminal B (n = 165), or high-risk subtype (luminal HER2, n = 22; HER2
      enriched, n = 13; basal like, n = 30; or triple-negative nonbasal, n = 6). Median
      follow-up was 10 years. RESULTS: Classification by subtype was prognostic for IBR
      (10-year estimates: luminal A, 5.2%; luminal B, 10.5%; high-risk subtypes, 21.3%;
      P < .001). Luminal subtypes seemed to derive less benefit from RT (luminal A
      hazard ratio [HR], 0.40; luminal B HR, 0.51) than high-risk subtypes (HR, 0.13);
      however, the overall subtype-treatment interaction term was not significant (P =
      .26). In an exploratory analysis of women with clinical low-risk (age older than
      60 years, T1, grade 1 or 2) luminal A tumors (n = 151), 10-year IBR was 3.1%
      versus 11.8% for the high-risk cohort (n = 341; P = .0063). Clinical low-risk
      luminal A patients had a 10-year IBR of 1.3% with tamoxifen versus 5.0% with
      tamoxifen plus RT (P = .42). Multivariable analysis showed that RT (HR, 0.31; P <
      .001), clinical risk group (HR, 2.2; P = .025), and luminal A subtype (HR, 0.25;
      P < .001) were significantly associated with IBR. CONCLUSION: IHC subtyping was
      prognostic for IBR but was not predictive of benefit from RT. Further studies may
      validate the exploratory finding of a low-risk luminal A group who may be spared
      breast RT.

PMID- 25964247
TI  - Hepatitis B Virus Screening for Patients With Cancer Before Therapy: American
      Society of Clinical Oncology Provisional Clinical Opinion Update.
AB  - PURPOSE: This updated provisional clinical opinion presents a revised opinion
      based on American Society of Clinical Oncology panel consensus in the context of
      an evolving database. CONTEXT: Despite the 2010 provisional clinical opinion
      recommendation, there is still evidence of suboptimal hepatitis B virus (HBV)
      screening among patients at high risk for HBV infection or HBV reactivation after
      chemotherapy. This updated provisional clinical opinion introduces a risk
      adaptive strategy to identify and treat patients with HBV infection to reduce
      their risk of HBV reactivation. PROVISIONAL CLINICAL OPINION: Medical providers
      should screen by testing patients for HBV infection before starting anti-CD20
      therapy or hematopoietic cell transplantation. Providers should also screen
      patients with risk factors for HBV infection. Screening should include both
      hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc),
      because reactivation can occur in patients who are HBsAg positive/anti-HBc
      positive or HBsAg negative/anti-HBc positive. Either total anti-HBc or anti-HBc
      immunoglobulin G (not immunoglobulin M) test should be used. Clinicians should
      start antiviral therapy for HBsAg-positive/anti-HBc-positive patients before or
      contemporaneously with cancer therapy and monitor HBsAg-negative/anti-HBc
      positive patients for reactivation with HBV DNA and ALT levels, promptly starting
      antivirals if reactivation occurs. Clinicians can initiate antivirals for HBsAg
      negative/anti-HBc-positive patients anticipating cancer therapies associated with
      a high risk of reactivation, or they can monitor HBV DNA and ALT levels and
      initiate on-demand antivirals. For patients who neither have HBV risk factors nor
      anticipate cancer therapy associated with a high risk of reactivation, current
      evidence does not support HBV screening before initiation of cancer therapy. Two
      panel members provided a minority viewpoint, involving a strategy of universal
      HBsAg and selective anti-HBc testing.

PMID- 25964248
TI  - Swinging for the Fences: Long-Term Survival With Ipilimumab in Metastatic
      Melanoma.
AB  - A 40-year-old man with stage III melanoma arising from his left shoulder
      underwent wide local excision, sentinel lymph node biopsy, and lymph node
      dissection. Nine months after receiving adjuvant biochemotherapy with cisplatin,
      vinblastine, dacarbazine, interleukin-2 (IL-2), and interferon alfa as part of a
      clinical trial, he developed headaches and right-hand weakness and was found to
      have a 2-cm left parietal CNS metastasis. A comprehensive staging workup
      identified multiple nonspecific subcentimeter pulmonary nodules. The brain mass
      was resected and confirmed to be metastatic melanoma; the surgical bed was
      treated with stereotactic radiosurgery. He was monitored off therapy, but 5
      months later, he developed a second left parietal CNS metastasis and enlarging
      lung nodules. The new brain lesion was treated with stereotactic radiosurgery,
      and he began systemic therapy with ipilimumab on a clinical trial. After the
      third dose, he presented with headache, nausea, and vomiting; a brain magnetic
      resonance imaging scan showed left anterior temporal enhancement, possibly
      representing new disease. His symptoms improved with a course of corticosteroids.
      Restaging of the chest showed a mixed response among the pulmonary nodules. After
      tapering off corticosteroids, he received the fourth dose of ipilimumab, which
      was complicated by grade 3 transaminitis and hypophysitis with documented
      hypothyroidism and adrenal insufficiency. They were managed with corticosteroids
      and thyroid and adrenal hormone replacement. Restaging scans showed further
      disease regression except for new confluent enhancing nodules and edema in the
      left temporal lobe. Craniotomy and resection of this area showed only necrotic
      tissue with no viable melanoma cells. Nine years after treatment with ipilimumab,
      he is alive and shows no evidence of melanoma on the basis of annual computed
      tomography scans of the chest, abdomen, and pelvis and magnetic resonance imaging
      scans of the brain. He has full neurologic function but still requires hormone
      replacement for persistent hypopituitarism.

PMID- 25964249
TI  - Prediagnostic Sex Steroid Hormones in Relation to Male Breast Cancer Risk.
AB  - PURPOSE: Although previous studies have implicated a variety of hormone-related
      risk factors in the etiology of male breast cancers, no previous studies have
      examined the effects of endogenous hormones. PATIENTS AND METHODS: Within the
      Male Breast Cancer Pooling Project, an international consortium comprising 21
      case-control and cohort investigations, a subset of seven prospective cohort
      studies were able to contribute prediagnostic serum or plasma samples for hormone
      quantitation. Using a nested case-control design, multivariable unconditional
      logistic regression analyses estimated odds ratios and 95% CIs for associations
      between male breast cancer risk and 11 individual estrogens and androgens, as
      well as selected ratios of these analytes. RESULTS: Data from 101 cases and 217
      matched controls were analyzed. After adjustment for age and date of blood draw,
      race, and body mass index, androgens were found to be largely unrelated to risk,
      but circulating estradiol levels showed a significant association. Men in the
      highest quartile had an odds ratio of 2.47 (95% CI, 1.10 to 5.58) compared with
      those in the lowest quartile (trend P = .06). Assessment of estradiol as a ratio
      to various individual androgens or sum of androgens showed no further enhancement
      of risk. These relations were not significantly modified by either age or body
      mass index, although estradiol was slightly more strongly related to breast
      cancers occurring among younger (age < 67 years) than older men. CONCLUSION: Our
      results support the notion of an important role for estradiol in the etiology of
      male breast cancers, similar to female breast cancers.

PMID- 25964251
TI  - Personalized Radiation Oncology for Breast Cancer: The New Frontier.

PMID- 25964250
TI  - SWOG S0809: A Phase II Intergroup Trial of Adjuvant Capecitabine and Gemcitabine
      Followed by Radiotherapy and Concurrent Capecitabine in Extrahepatic
      Cholangiocarcinoma and Gallbladder Carcinoma.
AB  - PURPOSE: The role of postoperative therapy in extrahepatic cholangiocarcinoma
      (EHCC) or gallbladder carcinoma (GBCA) is unknown. S0809 was designed to estimate
      2-year survival (overall and after R0 or R1 resection), pattern of relapse, and
      toxicity in patients treated with this adjuvant regimen. PATIENTS AND METHODS:
      Eligibility criteria included diagnosis of EHCC or GBCA after radical resection,
      stage pT2-4 or N+ or positive resection margins, M0, and performance status 0 to
      1. Patients received four cycles of gemcitabine (1,000 mg/m(2) intravenously on
      days 1 and 8) and capecitabine (1,500 mg/m(2) per day on days 1 to 14) every 21
      days followed by concurrent capecitabine (1,330 mg/m(2) per day) and radiotherapy
      (45 Gy to regional lymphatics; 54 to 59.4 Gy to tumor bed). With 80 evaluable
      patients, results would be promising if 2-year survival 95% CI were > 45% and R0
      and R1 survival estimates were >= 65% and 45%, respectively. RESULTS: A total of
      79 eligible patients (R0, n = 54; R1, n = 25; EHCC, 68%; GBCA, 32%) were treated
      (86% completed). For all patients, 2-year survival was 65% (95% CI, 53% to 74%);
      it was 67% and 60% in R0 and R1 patients, respectively. Median overall survival
      was 35 months (R0, 34 months; R1, 35 months). Local, distant, and combined
      relapse occurred in 14, 24, and nine patients. Grade 3 and 4 adverse effects were
      observed in 52% and 11% of patients, respectively. The most common grade 3 to 4
      adverse effects were neutropenia (44%), hand-foot syndrome (11%), diarrhea (8%),
      lymphopenia (8%), and leukopenia (6%). There was one death resulting from GI
      hemorrhage. CONCLUSION: This combination was well tolerated, has promising
      efficacy, and provides clinicians with a well-supported regimen. Our trial
      establishes the feasibility of conducting national adjuvant trials in EHCC and
      GBCA and provides baseline data for planning future phase III trials.

PMID- 25964253
TI  - Simpson's Paradox and the Impact of Different DNMT3A Mutations on Outcome in
      Younger Adults With Acute Myeloid Leukemia.
AB  - PURPOSE: To evaluate the impact of DNMT3A mutations on outcome in younger
      patients with cytogenetic intermediate-risk acute myeloid leukemia. PATIENTS AND
      METHODS: Diagnostic samples from 914 patients (97% < 60 years old) were screened
      for mutations in DNMT3A exons 13 to 23. Clinical outcome was evaluated according
      to presence or absence of a mutation and stratified according to type of mutation
      (R882, non-R882 missense, or truncation). RESULTS: DNMT3A mutations (DNMT3A(MUT))
      were identified in 272 patients (30%) and associated with a poorer prognosis than
      wild-type DNMT3A, but the difference was only seen when the results were
      stratified according to NPM1 genotype. This example of Simpson's paradox results
      from the high coincidence of DNMT3A and NPM1 mutations (80% of patients with
      DNMT3A(MUT) had NPM1 mutations), where the two mutations have opposing prognostic
      impact. In the stratified analyses, relapse in patients with DNMT3A(MUT) was
      higher (hazard ratio, 1.35; 95% CI, 1.07 to 1.72; P = .01), and overall survival
      was lower (hazard ratio, 1.37; 95% CI, 1.12 to 1.87; P = .002). The impact of
      DNMT3A(MUT) did not differ according to NPM1 genotype (test for heterogeneity:
      relapse, P = .4; overall survival, P = .9). Further analysis according to the
      type of DNMT3A mutation indicated that outcome was comparable in patients with
      R882 and non-R882 missense mutants, whereas in those with truncation mutants, it
      was comparable to wild-type DNMT3A. CONCLUSION: These data confirm that presence
      of a DNMT3A mutation should be considered as a poor-risk prognostic factor,
      irrespective of the NPM1 genotype, and suggest that further consideration should
      be given to the type of DNMT3A mutation.

PMID- 25964252
TI  - Racial and Ethnic Differences in Breast Cancer Survival: Mediating Effect of
      Tumor Characteristics and Sociodemographic and Treatment Factors.
AB  - PURPOSE: To evaluate the relationship between race/ethnicity and breast cancer
      specific survival according to subtype and explore mediating factors. PATIENTS
      AND METHODS: Participants were women presenting with stage I to III breast cancer
      between January 2000 and December 2007 at National Comprehensive Cancer Network
      centers with survival follow-up through December 2009. Cox proportional hazards
      regression was used to compare breast cancer-specific survival among Asians (n =
      533), Hispanics (n = 1,122), and blacks (n = 1,345) with that among whites (n =
      14,268), overall and stratified by subtype (luminal A like, luminal B like, human
      epidermal growth factor receptor 2 type, and triple negative). Model estimates
      were used to derive mediation proportion and 95% CI for selected risk factors.
      RESULTS: In multivariable adjusted models, overall, blacks had 21% higher risk of
      breast cancer-specific death (hazard ratio [HR], 1.21; 95% CI, 1.00 to 1.45). For
      estrogen receptor-positive tumors, black and white survival differences were
      greatest within 2 years of diagnosis (years 0 to 2: HR, 2.65; 95% CI, 1.34 to
      5.24; year 2 to end of follow-up: HR, 1.50; 95% CI, 1.12 to 2.00). Blacks were
      76% and 56% more likely to die as a result of luminal A-like and luminal B-like
      tumors, respectively. No disparities were observed for triple-negative or human
      epidermal growth factor receptor 2-type tumors. Asians and Hispanics were less
      likely to die as a result of breast cancer compared with whites (Asians: HR,
      0.56; 95% CI, 0.37 to 0.85; Hispanics: HR, 0.74; 95% CI, 0.58 to 0.95). For
      blacks, tumor characteristics and stage at diagnosis were significant disparity
      mediators. Body mass index was an important mediator for blacks and Asians.
      CONCLUSION: Racial disparities in breast cancer survival vary by tumor subtype.
      Interventions are needed to reduce disparities, particularly in the first 2 years
      after diagnosis among black women with estrogen receptor-positive tumors.

PMID- 25964254
TI  - Volunteering in Honduras: Results and Reflections.

PMID- 25964256
TI  - Cardiac Monitoring During Adjuvant Trastuzumab-Based Chemotherapy Among Older
      Patients With Breast Cancer.
AB  - PURPOSE: Patients treated with adjuvant trastuzumab require adequate cardiac
      monitoring. We describe the patterns of cardiac monitoring and evaluate factors
      associated with adequate monitoring in a large population-based study of older
      patients with breast cancer. PATIENTS AND METHODS: Patients age 66 years or older
      with full Medicare coverage, diagnosed with stage I to III breast cancer between
      2005 and 2009, and treated with adjuvant trastuzumab-based chemotherapy were
      identified in the SEER-Medicare and the Texas Cancer Registry-Medicare databases.
      The adequacy of cardiac monitoring was determined. Chemotherapy, trastuzumab use,
      cardiac monitoring, and comorbidities were identified by using International
      Classification of Diseases, 9th revision and Healthcare Common Procedure Coding
      System codes. Prescribing physician characteristics were also evaluated. Analyses
      included descriptive statistics and multilevel logistic regression models.
      RESULTS: In all, 2,203 patients were identified; median age was 72 years.
      Adequate monitoring was identified in only 36.0% of the patients (n = 793). In
      the multivariable model, factors associated with optimal cardiac monitoring
      included a more recent year of diagnosis (hazard ratio [HR], 1.83; 95% CI, 1.32
      to 2.54), anthracycline use (HR, 1.39; 95% CI, 1.14 to 1.71), female prescribing
      physician (HR, 1.37; 95% CI, 1.10 to 1.70), and physician graduating after 1990
      (HR, 1.66; 95% CI, 1.29 to 2.12). The presence of cardiac comorbidities was not a
      determinant for cardiac monitoring. Of the variance in the adequacy of cardiac
      monitoring, 15.3% was attributable to physician factors and 5.2% to measured
      patient factors. CONCLUSION: A large proportion of patients had suboptimal
      cardiac monitoring. Physician characteristics had more influence than measured
      patient-level factors in the adequacy of cardiac monitoring. Because trastuzumab
      related cardiotoxicity is reversible, efforts to improve the adequacy of cardiac
      monitoring are needed, particularly in vulnerable populations.

PMID- 25964255
TI  - Risk Algorithm Using Serial Biomarker Measurements Doubles the Number of Screen
      Detected Cancers Compared With a Single-Threshold Rule in the United Kingdom
      Collaborative Trial of Ovarian Cancer Screening.
AB  - PURPOSE: Cancer screening strategies have commonly adopted single-biomarker
      thresholds to identify abnormality. We investigated the impact of serial
      biomarker change interpreted through a risk algorithm on cancer detection rates.
      PATIENTS AND METHODS: In the United Kingdom Collaborative Trial of Ovarian Cancer
      Screening, 46,237 women, age 50 years or older underwent incidence screening by
      using the multimodal strategy (MMS) in which annual serum cancer antigen 125 (CA
      125) was interpreted with the risk of ovarian cancer algorithm (ROCA). Women were
      triaged by the ROCA: normal risk, returned to annual screening; intermediate
      risk, repeat CA-125; and elevated risk, repeat CA-125 and transvaginal
      ultrasound. Women with persistently increased risk were clinically evaluated. All
      participants were followed through national cancer and/or death registries.
      Performance characteristics of a single-threshold rule and the ROCA were compared
      by using receiver operating characteristic curves. RESULTS: After 296,911 women
      years of annual incidence screening, 640 women underwent surgery. Of those, 133
      had primary invasive epithelial ovarian or tubal cancers (iEOCs). In all, 22
      interval iEOCs occurred within 1 year of screening, of which one was detected by
      ROCA but was managed conservatively after clinical assessment. The sensitivity
      and specificity of MMS for detection of iEOCs were 85.8% (95% CI, 79.3% to 90.9%)
      and 99.8% (95% CI, 99.8% to 99.8%), respectively, with 4.8 surgeries per iEOC.
      ROCA alone detected 87.1% (135 of 155) of the iEOCs. Using fixed CA-125 cutoffs
      at the last annual screen of more than 35, more than 30, and more than 22 U/mL
      would have identified 41.3% (64 of 155), 48.4% (75 of 155), and 66.5% (103 of
      155), respectively. The area under the curve for ROCA (0.915) was significantly
      (P = .0027) higher than that for a single-threshold rule (0.869). CONCLUSION:
      Screening by using ROCA doubled the number of screen-detected iEOCs compared with
      a fixed cutoff. In the context of cancer screening, reliance on predefined single
      threshold rules may result in biomarkers of value being discarded.

PMID- 25964257
TI  - Weight Lifting and Physical Function Among Survivors of Breast Cancer: A Post Hoc
      Analysis of a Randomized Controlled Trial.
AB  - PURPOSE: Survivors of breast cancer may experience deterioration of physical
      function. This is important because poor physical function may be associated with
      premature mortality, injurious falls, bone fracture, and disability. We conducted
      a post hoc analysis to explore the potential efficacy of slowly progressive
      weight lifting to reduce the incidence of physical function deterioration among
      survivors of breast cancer. METHODS: Between October 2005 and August 2008, we
      conducted a single-blind, 12-month, randomized controlled trial of twice-per-week
      slowly progressive weight lifting or standard care among 295 survivors of
      nonmetastatic breast cancer. In this post hoc analysis of data from the Physical
      Activity and Lymphedema Trial, we examined incident deterioration of physical
      function after 12 months, defined as a >= 10-point decrease in the physical
      function subscale of the Medical Outcomes Short-Form 36-item questionnaire.
      RESULTS: The proportion of participants who experienced incident physical
      function deterioration after 12 months was 16.3% (24/147) in the control group
      and 8.1% (12/148) in the weight lifting group (relative risk, 0.49; 95% CI, 0.25
      to 0.96; P = .04). No serious or unexpected adverse events occurred that were
      related to weight lifting. CONCLUSION: Slowly progressive weight lifting compared
      with standard care reduced the incidence of physical function deterioration among
      survivors of breast cancer. These data are hypothesis generating. Future studies
      should directly compare the efficacy of weight lifting with other modalities of
      exercise, such as brisk walking, to appropriately inform the development of a
      confirmatory study designed to preserve physical function among survivors of
      breast cancer.

PMID- 25964258
TI  - Menthol Enhances the Desensitization of Human alpha3beta4 Nicotinic Acetylcholine
      Receptors.
AB  - The alpha3beta4 nicotinic acetylcholine receptor (nAChR) subtype is widely
      expressed in the peripheral and central nervous systems, including in airway
      sensory nerves. The nAChR subtype transduces the irritant effects of nicotine in
      tobacco smoke and, in certain brain areas, may be involved in nicotine addiction
      and/or withdrawal. Menthol, a widely used additive in cigarettes, is a potential
      analgesic and/or counterirritant at sensory nerves and may also influence
      nicotine's actions in the brain. We examined menthol's effects on recombinant
      human alpha3beta4 nAChRs and native nAChRs in mouse sensory neurons. Menthol
      markedly decreased nAChR activity as assessed by Ca(2+) imaging, (86)Rb(+)
      efflux, and voltage-clamp measurements. Coapplication of menthol with
      acetylcholine or nicotine increased desensitization, demonstrated by an increase
      in the rate and magnitude of the current decay and a reduction of the current
      integral. These effects increased with agonist concentration. Pretreatment with
      menthol followed by its washout did not affect agonist-induced desensitization,
      suggesting that menthol must be present during the application of agonist to
      augment desensitization. Notably, menthol acted in a voltage-independent manner
      and reduced the mean open time of single channels without affecting their
      conductance, arguing against a simple channel-blocking effect. Further, menthol
      slowed or prevented the recovery of nAChRs from desensitization, indicating that
      it probably stabilizes a desensitized state. Moreover, menthol at concentrations
      up to 1 mM did not compete for the orthosteric nAChR binding site labeled by
      [(3)H]epibatidine. Taken together, these data indicate that menthol promotes
      desensitization of alpha3beta4 nAChRs by an allosteric action. 

PMID- 25964259
TI  - Genome-wide study of mRNA degradation and transcript elongation in Escherichia
      coli.

PMID- 25964260
TI  - Parental Age at Birth and Risk of Hematological Malignancies in Older Adults.
AB  - The proportion of parents aged >=35 years at the birth of their child continues
      to increase, but long-term health consequences for these children are not fully
      understood. A recent prospective study of 110,999 adult women showed an
      association between paternal-but not maternal-age at birth and sporadic
      hematological cancer risk. To further investigate this topic, we examined these
      associations in women and men in the American Cancer Society Cancer Prevention
      Study-II Nutrition Cohort. Among 138,003 Cancer Prevention Study-II participants,
      2,532 incident hematological cancers were identified between 1992 and 2009.
      Multivariable-adjusted hazard ratios and 95% confidence intervals were computed
      by using Cox proportional hazards regression. There was no clear linear trend in
      the risk of hematological malignancies by either paternal or maternal age.
      However, there was a strong, positive association with paternal age among
      participants without siblings. In that group, the hazard ratio for fathers aged
      >=35 years compared with <25 years at birth was 1.63 (95% confidence interval:
      1.19, 2.23), and a linear dose-response association was suggested (Pspline =
      0.002).There were no differences by subtype of hematological cancer. Results of
      this study support the need for further research to better understand the
      association between paternal age at birth and hematological malignancies. 

PMID- 25964261
TI  - Comparison of Interviewer-Administered and Automated Self-Administered 24-Hour
      Dietary Recalls in 3 Diverse Integrated Health Systems.
AB  - Twenty-four-hour dietary recalls provide high-quality intake data but have been
      prohibitively expensive for large epidemiologic studies. This study's goal was to
      assess whether the web-based Automated Self-Administered 24-Hour Recall (ASA24)
      performs similarly enough to the standard interviewer-administered, Automated
      Multiple-Pass Method (AMPM) 24-hour dietary recall to be considered a viable
      alternative. In 2010-2011, 1,081 adults from 3 integrated health systems in
      Detroit, Michigan; Marshfield, Wisconsin; and Kaiser-Permanente Northern
      California participated in a field trial. A quota design ensured a diverse sample
      by sex, age, and race/ethnicity. Each participant was asked to complete 2 recalls
      and was randomly assigned to 1 of 4 protocols differing by type of recall and
      administration order. For energy, the mean intakes were 2,425 versus 2,374 kcal
      for men and 1,876 versus 1,906 kcal for women by AMPM and ASA24, respectively. Of
      20 nutrients/food groups analyzed and controlling for false discovery rate, 87%
      were judged equivalent at the 20% bound. ASA24 was preferred over AMPM by 70% of
      the respondents. Attrition was lower in the ASA24/AMPM study group than in the
      AMPM/ASA24 group, and it was lower in the ASA24/ASA24 group than in the AMPM/AMPM
      group. ASA24 offers the potential to collect high-quality dietary intake
      information at low cost with less attrition. 

PMID- 25964262
TI  - Facilitating translational research.

PMID- 25964265
TI  - Skin under the (Spot)-Light: Cross-Talk with the Central Hypothalamic-Pituitary
      Adrenal (HPA) Axis.
AB  - UV radiation is among the most prevalent stressors in humans and diurnal rodents,
      exerting direct and indirect DNA damage, free-radical production, and interaction
      with specific chromophores that affects numerous biological processes. In
      addition to its panoply of effects, UVB (290-320 nm) radiation can specifically
      affect various local neuroendocrine activities by stimulating the expression of
      corticotropin-releasing hormone (CRH), urocortin, proopiomelanocortin (POMC), and
      POMC-derived peptides. Although very little is known about the interplay between
      the central hypothalamic-pituitary-adrenal (HPA) axis and the skin HPA axis
      analog, in the current issue Skobowiat and Slominski propose a novel mechanism by
      which exposure to UVB activates a local HPA axis in skin, which in turn activates
      the central HPA axis, with the requirement of a functional pituitary gland. This
      is the first evidence of the local HPA axis in skin contributing to the central
      neuroendocrine response. This raises intriguing possibilities regarding how local
      production of cortisol and other HPA axis molecules in skin influence overall
      systemic levels of cortisol and help regulate local and central HPA axes in the
      context of homeostasis, skin injury, and inflammatory skin disorders. 

PMID- 25964266
TI  - Docosahexaenoic Acid alleviates atopic dermatitis in mice by generating T
      regulatory cells and m2 macrophages.
AB  - Han et al. (this issue) describe a novel mechanism by which docosahexaenoic acid
      (DHA) may suppress atopic dermatitis symptoms in mice. They find that DHA induces
      FoxP3 T regulatory cells in vivo, M2 macrophages drive transforming growth factor
      beta and IL-10 conversion of CD4 T cells to CD4 FoxP3 T regulatory cells in
      vitro, and DHA-treated M2 macrophages suppress atopic dermatitis in mice. 

PMID- 25964267
TI  - Erythrokeratodermia variabilis et progressiva allelic to oculo-dento-digital
      dysplasia.
AB  - Erythrokeratodermia variabilis et progressiva (EKVP) is a genodermatosis with
      clinical and genetic heterogeneity, most often transmitted in an autosomal
      dominant manner, caused by mutations in GJB3 and GJB4 genes encoding connexins
      (Cx)31 and 30.3, respectively. In this issue, Boyden et al. (2015) report for the
      first time de novo dominant mutations in GJA1 encoding the ubiquitous Cx43 in
      patients with EKVP. These results expand the genetic heterogeneity of EKVP and
      the human disease phenotypes associated with GJA1 mutations. They disclose that
      EKVP is allelic to oculo-dento-digital dysplasia, a rare syndrome previously
      known to be caused by dominant GJA1 mutations. 

PMID- 25964268
TI  - FICZ: A Messenger of Light in Human Skin.
AB  - Photosensitization, subsequent to photon absorption by chromophores present in
      the human skin, appears to be a key mechanism of UV-induced oxidative stress. The
      tryptophan photoproduct 6-formylindolo[3,2-b]carbazole (FICZ), an aryl
      hydrocarbon receptor ligand, has been found to be a potent UVA photosensitizer,
      effective at nanomolar concentrations. A novel addition to the family of
      endogenous photosensitizers, the precise mechanism(s) through which it mediates
      oxidative stress in UVA exposed skin and its response to the UVB spectrum of the
      solar UV flux remains unexplored. Further studies related to its functionality in
      the human skin, its utility as a tool against UV-induced adverse effects, and its
      role in inflammatory skin diseases will have the potential to open up new avenues
      in the realms of human skin photobiology. 

PMID- 25964269
TI  - Hairy math: addition of Wnt-3a to multiply bulge cells.
AB  - Canonical Wnt signals are important for activation of epithelial skin stem cells,
      but the role of individual Wnt ligands remains uncertain. Ouji et al. demonstrate
      a key role for Wnt-3a in partial maintenance and long-term expansion of
      epithelial skin stem cells in vitro. They also report a method for expanding
      these cells in vitro without feeder cells. 

PMID- 25964270
TI  - Cells to surgery quiz: June 2015.

PMID- 25964271
TI  - JID VisualDx Quiz: June 2015.

PMID- 25964272
TI  - What is a pragmatic clinical trial?

PMID- 25964274
TI  - Hip Joint Pathology as a Leading Cause of Groin Pain in the Sporting Population:
      A 6-Year Review of 894 Cases.
AB  - BACKGROUND: Chronic hip and groin pain offers a diagnostic challenge for the
      sports medicine practitioner. Recent consensus suggests diagnostic categorization
      based on 5 clinical entities: hip joint-, adductor-, pubic bone stress injury-,
      iliopsoas-, or abdominal wall-related pathology. However, their prevalence
      patterns and coexistence in an active population are unclear. PURPOSE: This study
      presents a descriptive epidemiology based on a large sample of active individuals
      with long-standing pain in the hip and groin region. The objectives were to
      examine the prevalence of key clinical entities, document coexisting pathologies,
      and present prevalence patterns based on key demographics. STUDY DESIGN: Cross
      sectional study; Level of evidence, 3. METHODS: A retrospective review was
      conducted of clinical records of all hip and groin injuries seen between January
      2006 and December 2011 under the care of a single experienced sports medicine
      consultant. In all cases, imaging was undertaken by a team of specialist
      musculoskeletal radiologists. Diagnoses were categorized according to 5 clinical
      entities using contemporary diagnostic nomenclature. The chi-square test was used
      to compare observed and expected frequencies across each subgroup's prevalence
      figures based on sex, age, and sports participation. RESULTS: Full medical
      records were retrieved from 894 patients with chronic hip and groin pain. The
      majority of patients were male (73%), aged between 26 and 30 years, and
      participating in footballing codes (soccer, rugby, and Gaelic sports) or running.
      A total of 24 combinations of clinical entities were found. There were
      significant differences (P < .001) in prevalence patterns based on age, sex, and
      sports activity. Adductor-related pain or pubic bone stress injury rarely
      presented in isolation. Hip joint pathology was the most common clinical entity
      (55.98%) and was significantly more likely to present in isolation. The majority
      of hip joint pathologies related to femoroacetabular impingement (40%), labral
      tears (33%), and osteoarthritis (24%). These figures were significantly different
      across male and female patients (P < .001), with a higher percentage of cases of
      femoroacetabular impingement and labral tears in male and female patients,
      respectively. CONCLUSION: Chronic hip and groin pain is often associated with
      multiple clinical entities. Hip joint pathology is the most common clinical
      entity and is most likely to relate to femoroacetabular impingement, labral
      tears, and osteoarthritis. These pathologies seem to be associated with secondary
      breakdown of surrounding structures; however, underpinning mechanisms are
      unclear.

PMID- 25964275
TI  - Childhood Maltreatment and Development of Substance Use Disorders: A Review and a
      Model of Cognitive Pathways.
AB  - Exposure to childhood maltreatment (CM) is associated with increased risk for
      developing substance use disorders (SUDs). CM exerts negative effects on
      cognitive abilities including intellectual performance, memory, attention, and
      executive function. Parallel cognitive impairments have been observed in SUDs.
      Hence, limited studies have examined the mediating effect of cognitive
      impairments in the relationship between CM and SUDs. In addition, most studies
      used concurrent self-report assessments in adult populations. Longitudinal
      studies that investigated the long-term consequences of CM on psychopathology,
      including SUDs, throughout childhood, adolescence, and adulthood are rare. Thus,
      the underlying developmental pathways between CM and SUDs are not clearly
      understood. In this article, we review the evidence that cognitive impairments
      mediate, at least in part, the relationship between CM and development of SUDs
      and propose a model that explains how CM increases the risk for SUDs through the
      development of a cognitive framework of vulnerability.

PMID- 25964276
TI  - Relational Patterns Between Caregivers With PTSD and Their Nonexposed Children: A
      Review.
AB  - The question as to whether or not children can be affected by the traumatization
      of their parents has been the topic of a long-standing debate. This article
      provides a critical review of 72 research studies on traumatized parents with
      symptoms of posttraumatic stress disorder (PTSD), the parent-child interaction,
      and the impact on their nonexposed child (0-18 years). The evidence suggests that
      traumatization can cause parenting limitations, and these limitations can disrupt
      the development of the young child. From the studies reviewed several patterns
      emerged: Relational patterns of traumatized parents who are observed to be
      emotionally less available and who perceive their children more negatively than
      parents without symptoms of PTSD; relational patterns of children who at a young
      age are easily deregulated or distressed and at an older age are reported to face
      more difficulties in their psychosocial development than children of parents
      without symptoms of PTSD; and relational patterns that show remarkable
      similarities to relational patterns between depressed or anxious parents and
      their children. Mechanisms such as mentalization, attachment, physiological
      factors, and the cycle of abuse offer a valuable perspective to further our
      understanding of the relational patterns. This article builds on previous work by
      discussing the emerged patterns between traumatized parents and their nonexposed
      children from a relational and transactional perspective. 

PMID- 25964273
TI  - Silver nanoparticles: correlating nanoparticle size and cellular uptake with
      genotoxicity.
AB  - The focus of this research was to develop a better understanding of the pertinent
      physico-chemical properties of silver nanoparticles (AgNPs) that affect
      genotoxicity, specifically how cellular uptake influences a genotoxic cell
      response. The genotoxicity of AgNPs was assessed for three potential mechanisms:
      mutagenicity, clastogenicity and DNA strand-break-based DNA damage. Mutagenicity
      (reverse mutation assay) was assessed in five bacterial strains of Salmonella
      typhimurium and Echerichia coli, including TA102 that is sensitive to oxidative
      DNA damage. AgNPs of all sizes tested (10, 20, 50 and 100nm), along with silver
      nitrate (AgNO3), were negative for mutagenicity in bacteria. No AgNPs could be
      identified within the bacteria cells using transmission electron microscopy
      (TEM), indicating these bacteria lack the ability to actively uptake AgNPs 10nm
      or larger. Clastogenicity (flow cytometry-based micronucleus assay) and
      intermediate DNA damage (DNA strand breaks as measured in the Comet assay) were
      assessed in two mammalian white blood cell lines: Jurkat Clone E6-1 and THP-1. It
      was observed that micronucleus and Comet assay end points were inversely
      correlated with AgNP size, with smaller NPs inducing a more genotoxic response.
      TEM results indicated that AgNPs were confined within intracellular vesicles of
      mammalian cells and did not penetrate the nucleus. The genotoxicity test results
      and the effect of AgNO3 controls suggest that silver ions may be the primary, and
      perhaps only, cause of genotoxicity. Furthermore, since AgNO3 was not mutagenic
      in the gram-negative bacterial Ames strains tested, the lack of bacterial uptake
      of the AgNPs may not be the major reason for the lack of genotoxicity observed. 

PMID- 25964277
TI  - Survivor Perspectives on IPV Perpetrator Interventions: A Systematic Narrative
      Review.
AB  - More effective work with perpetrators of intimate partner violence (IPV) can be
      built upon a better understanding of how and why they change their behavior. This
      article presents a systematic narrative review of female IPV survivor
      perspectives on the changes brought about by IPV perpetrator programs. Fourteen
      databases and web search engines were searched and 16 articles reporting relevant
      qualitative findings were identified. Survivors often reported some level of
      positive change through their partner's engagement with a program, but the
      sustainability of this change is unclear and there was also some negative
      feedback. From the survivors' perspective, key barriers to perpetrator change
      include alcohol dependency, mental health challenges, relationship dynamics, and
      their family of origin. Mechanisms by which perpetrators are held to account,
      namely, survivor validation and judicial measures, were seen as central to the
      change process. Survivors perceived changes in perpetrator behavior (the use of
      conflict interruption techniques and new communication skills) and changes in
      perpetrators' belief systems (adopting new perspectives). Changes in belief
      systems were associated with more complete desistence from violence and would
      appear more difficult to effect. The review highlights the complexity in this
      field, which is discussed by the authors with reference to practice, policy, and
      research.

PMID- 25964278
TI  - Secondary Traumatization in Mental Health Professionals: A Systematic Review of
      Gender Findings.
AB  - The issue of gender is largely ignored in studies of secondary traumatization
      (STS). This article addresses the question of gender differences in
      susceptibility to STS among clinicians who treat traumatized clients. It does so
      by systematically reviewing the very limited body of published findings on this
      subject to date. These are 10 published studies that measure STS by post
      traumatic stress disorder (PTSD) symptomatology and 4 studies that measure it
      using Stamm's Professionals Quality of Life Survey (ProQOL), which queries PTSD
      symptomatology along with other difficulties that may arise in helping
      traumatized clients. Almost all the studies based on PTSD symptomatology show
      greater female susceptibility. Although the pattern is less clear in the ProQOL
      studies, the article argues that the research to date does not really show mixed
      findings, as is repeatedly claimed, but greater susceptibility among female
      clinicians. It also points out that the findings do not mean that male clinicians
      are unaffected by their traumatized clients and notes the various manifestations
      of their distress reported in the reviewed studies. The article offers a variety
      of explanations for the heightened female susceptibility. 

PMID- 25964280
TI  - A cold taken to heart.

PMID- 25964282
TI  - Ductus arteriosus aneurysm and vocal cord paralysis.

PMID- 25964279
TI  - Emerging concepts in the molecular basis of pulmonary arterial hypertension: part
      I: metabolic plasticity and mitochondrial dynamics in the pulmonary circulation
      and right ventricle in pulmonary arterial hypertension.

PMID- 25964283
TI  - One-stage off-pump transapical mitral valve repair and aortic valve replacement.

PMID- 25964284
TI  - Letter by Aldasouqi and Abela Regarding Article, "Prognostic Value of Fasting
      Versus Nonfasting Low-Density Lipoprotein Cholesterol Levels on Long-Term
      Mortality: Insight From the National Health and Nutrition Survey III (NHANES
      III)".

PMID- 25964285
TI  - Letter by Horne et al Regarding Article, "Prognostic Value of Fasting Versus
      Nonfasting Low-Density Lipoprotein Cholesterol Levels on Long-Term Mortality:
      Insight From the National Health and Nutrition Survey III (NHANES-III)".

PMID- 25964286
TI  - Reply to Letters Regarding Article, "Prognostic Value of Fasting Versus
      Nonfasting Low-Density Lipoprotein Cholesterol Levels on Long-Term Mortality:
      Insight From the National Health and Nutrition Examination Survey III (NHANES
      III)".

PMID- 25964287
TI  - Correction.

PMID- 25964288
TI  - Correction.

PMID- 25964289
TI  - Vitamin D in Foot and Ankle Fracture Healing: A Literature Review and Research
      Design.
AB  - Vitamin D is a generic name for a group of essential vitamins, or secosteroids,
      important in calcium homeostasis and bone metabolism. Specifically, efficacy of
      vitamin D with regard to bone healing is in question. A literature review was
      performed, finding mostly large studies involving vitamin D effects on prevention
      of fractures and randomized animal model studies consisting of controlled
      fractures with vitamin D interventions. The prevention articles generally focus
      on at-risk populations, including menopausal women and osteoporotic patients, and
      also most often include calcium in the treatment group. Few studies look at
      vitamin D specifically. The animal model studies often focus more on vitamin D
      supplementation; however the results are still largely inconclusive. While recent
      case reports appear promising, the ambiguity of results on the topic of fracture
      healing suggests a need for more, higher level research. A novel study design is
      proposed to help determine the efficacy on vitamin D in fracture healing. LEVELS
      OF EVIDENCE: Therapeutic, Level IV: Systematic Review.

PMID- 25964290
TI  - Assessment of Foot Self-Care in Patients With Diabetes: Retrospective Assessment
      (2008-2014).
AB  - INTRODUCTION: The purpose of this article is to assess the current status of the
      relationship between foot self-care and self-examination and the development of
      complications of diabetes mellitus. METHODOLOGY: A systematic review of articles.
      We extracted assessments of health habits with regard to educational and training
      interventions intended for diabetic foot health care. We included clinical
      trials, meta-analysis, and Cochrane Reviews from 2008 to December 2014. RESULTS:
      We included 34 articles in this review. The initial number of articles selected
      was 35, including 12 from PubMed, 12 from Webs of Knowledge, and 4 Cochrane
      reviews that were considered valid as they complied with the requirements set:
      they related to interventions reducing foot complications caused by diabetes.
      CONCLUSION: Strategies aimed at behavioral changes are effective for the
      metabolic control of the disease and for the reduction of amputations. However,
      given the current methodology deficit existing in most studies with regard to
      sample selection and length of the study, it is necessary to validate a reliable
      tool or measurement to indicate the status of healthy behavior development and to
      sustain such measures over time. LEVELS OF EVIDENCE: Therapeutic, Level III:
      Systematic review of level I-III studies.

PMID- 25964291
TI  - Endovascular Versus Surgical Revascularization for the Management of Chronic
      Mesenteric Ischemia.
AB  - BACKGROUND: Chronic mesenteric ischemia (CMI) can be treated with surgical
      revascularization (SR) or endovascular revascularization (ER). MATERIALS AND
      METHODS: Systematic review of 12 studies comparing ER and SR in CMI. Primary end
      point was perioperative (30 days) survival. A secondary composite end point
      consisted of perioperative mortality, nonfatal cardiac events, nonfatal stroke,
      and nonfatal bowel ischemia. Further end points included late survival, primary
      patency, and symptom improvement. RESULTS: The cumulative odds ratio (OR) for
      perioperative mortality was 0.78 (95% confidence interval [CI]: 0.40-1.50, P =
      .45) and 0.56 (95% CI: 0.28-1.11, P = .10) for the composite end point. The
      cumulative OR for survival after the 30th day was 0.83 (95% CI: 0.47-1.46), P =
      .51. Late primary patency was reported in 8 studies, with a cumulative OR of 3.57
      (95% CI: 1.83-6.97, P = .0002)-favoring SR. CONCLUSION: In the first meta
      analysis to compare ER and SR in CMI, there were no differences in mortality and
      morbidity. Patency rates were better following SR.

PMID- 25964292
TI  - Anti-platelet and anti-hypertension medication use in patients with fibromuscular
      dysplasia: Results from the United States Registry for Fibromuscular Dysplasia.
AB  - Fibromuscular dysplasia (FMD), a non-inflammatory arterial disease, may lead to
      renovascular hypertension (HTN) and cerebrovascular disease. Little is known
      about medication use in FMD. Clinical features and medication use were reviewed
      in a national FMD registry (12 US sites). Medication usage was assessed in raw
      and adjusted analyses. Covariates included demographic characteristics, co-morbid
      conditions and vascular bed involvement. A total of 874 subjects (93.6% female)
      were included in the analysis. Mean age was 55.6+/-13.1 years, 74.5% had HTN,
      25.4% had a history of transient ischemic attack or stroke, and 7.5% had a
      history of coronary artery disease (CAD). Renal and cerebrovascular arteries were
      affected in 70.4% and 74.7%, respectively. Anti-platelet agents were administered
      to 72.9% of patients. In multivariate analyses, factors associated with a greater
      likelihood of anti-platelet agent use were older age (OR=1.02 per year, p=0.005),
      CAD (OR=3.76, p=0.015), cerebrovascular artery FMD involvement in isolation
      (OR=2.31, p<0.0001) or a history of previous intervention for FMD (OR=1.52,
      p=0.036). A greater number of anti-HTN medications was evident in isolated renal
      versus isolated cerebrovascular FMD patients. Factors associated with a greater
      number of anti-HTN medications were older age (OR=1.03 per year, p<0.0001),
      history of HTN (OR=24.04, p<0.0001), history of CAD (OR=2.71, p=0.0008) and a
      history of a previous therapeutic procedure (OR=1.72, p=0.001). In conclusion, in
      FMD, medication use varies based on vascular bed involvement. Isolated renal FMD
      patients receive more anti-HTN agents and there is greater anti-platelet agent
      use among patients with cerebrovascular FMD. Further studies correlating
      medication use in FMD with clinically meaningful patient outcomes are necessary. 

PMID- 25964293
TI  - Enhanced biogas production by anaerobic co-digestion from a trinary mix substrate
      over a binary mix substrate.
AB  - The synergetic enhancement of mesophilic anaerobic co-digestion of trinary and
      binary mix of organic fraction of municipal solid waste (OFMSW) + primary sludge
      (PS) + thickened waste activated sludge (TWAS) as substrates was investigated
      through batch biological methane potential (BMP) and semi-continuous flow reactor
      tests. Cumulative biogas yield (CBY) yield for the binary mix of OFMSW:TWAS was
      555, 580, and 660 mL/g volatile solids (VS)added for an OFMSW:TWAS ratio of
      25:75, 50:50, and 75:25, respectively, which was 48, 78.5, and 140% higher than
      the calculated expected biogas (CEB) yield from the corresponding individual
      substrates. The trinary mixture of OFMSW:TWAS:PS at ratios of 25:37.5:375.5,
      50:25:25 and 75:12.5:12.5 was able to produce 680, 710 and 780 mL/g VSadded,
      respectively, which was 25.5, 62.0 and 135.6% more biogas than the calculated
      expected biogas yield from the corresponding individual substrates. Cumulative
      methane yield (CMY) of trinary mixtures was also higher than the corresponding
      binary mixtures (20, 27, and 12 % increase for OFMSW:TWAS:PS at a ratio of
      25:37.5:37.5, 50:25:25, and 75:12.5:12.5 compared to the binary mix of OFMSW:TWAS
      at a ratio of 25:75, 50:50, and 75:25, respectively). Methane content of the
      biogas varied from 54 to 57%. The results from semi-continuous flow anaerobic
      reactors under hydraulic retention times (HRT) of 15, 10 and 7 days supported the
      results of batch biological methane potential tests. The results were conclusive
      that enhancement in biogas production was noticeably higher from the co-digestion
      of trinary mix of organic fraction of municipal solid waste+ thickened waste
      activated sludge + primary sludge than the binary mix organic fraction of
      municipal solid waste+thickened waste activated sludge or thickened waste
      activated sludge+primary sludge with concomitant improvements in VS removal and
      biodegradability for tri-digestion of organic fraction of municipal solid waste,
      thickened waste activated sludge and primary sludge.

PMID- 25964294
TI  - APO866 Increases Antitumor Activity of Cyclosporin-A by Inducing Mitochondrial
      and Endoplasmic Reticulum Stress in Leukemia Cells.
AB  - PURPOSE: The nicotinamide phosphoribosyltransferase (NAMPT) inhibitor, APO866,
      has been previously shown to have antileukemic activity in preclinical models,
      but its cytotoxicity in primary leukemia cells is frequently limited. The success
      of current antileukemic treatments is reduced by the occurrence of multidrug
      resistance, which, in turn, is mediated by membrane transport proteins, such as P
      glycoprotein-1 (Pgp). Here, we evaluated the antileukemic effects of APO866 in
      combination with Pgp inhibitors and studied the mechanisms underlying the
      interaction between these two types of agents. EXPERIMENTAL DESIGN: The effects
      of APO866 with or without Pgp inhibitors were tested on the viability of leukemia
      cell lines, primary leukemia cells (AML, n = 6; B-CLL, n = 19), and healthy
      leukocytes. Intracellular nicotinamide adenine dinucleotide (NAD(+)) and ATP
      levels, mitochondrial transmembrane potential (DeltaPsi(m)), markers of apoptosis
      and of endoplasmic reticulum (ER) stress were evaluated. RESULTS: The combination
      of APO866 with Pgp inhibitors resulted in a synergistic cytotoxic effect in
      leukemia cells, while sparing normal CD34(+) progenitor cells and peripheral
      blood mononuclear cells. Combining Pgp inhibitors with APO866 led to increased
      intracellular APO866 levels, compounded NAD(+) and ATP shortage, and induced
      DeltaPsi(m) dissipation. Notably, APO866, Pgp inhibitors and, to a much higher
      extent, their combination induced ER stress and ER stress inhibition strongly
      reduced the activity of these treatments. CONCLUSIONS: APO866 and Pgp inhibitors
      show a strong synergistic cooperation in leukemia cells, including acute
      myelogenous leukemia (AML) and B-cell chronic lymphocytic leukemia (B-CLL)
      samples. Further evaluations of the combination of these agents in clinical
      setting should be considered.

PMID- 25964295
TI  - Polymorphism at 19q13.41 Predicts Breast Cancer Survival Specifically after
      Endocrine Therapy.
AB  - PURPOSE: Although most patients with estrogen receptor (ER)-positive breast
      cancer benefit from endocrine therapies, a significant proportion do not. Our aim
      was to identify inherited genetic variations that might predict survival among
      patients receiving adjuvant endocrine therapies. EXPERIMENTAL DESIGN: We
      performed a meta-analysis of two genome-wide studies; Helsinki Breast Cancer
      Study, 805 patients, with 240 receiving endocrine therapy and Prospective study
      of Outcomes in Sporadic versus Hereditary breast cancer, 536 patients, with 155
      endocrine therapy patients, evaluating 486,478 single-nucleotide polymorphisms
      (SNP). The top four associations from the endocrine treatment subgroup were
      further investigated in two independent datasets totaling 5,011 patients, with
      3,485 receiving endocrine therapy. RESULTS: A meta-analysis identified a common
      SNP rs8113308, mapped to 19q13.41, associating with reduced survival among
      endocrine-treated patients [hazard ratio (HR), 1.69; 95% confidence interval
      (CI), 1.37-2.07; P = 6.34 * 10(-7)] and improved survival among ER-negative
      patients, with a similar trend in ER-positive cases not receiving endocrine
      therapy. In a multivariate analysis adjusted for conventional prognostic factors,
      we found a significant interaction between the rs8113308 and endocrine treatment,
      indicating a predictive, treatment-specific effect of the SNP rs8113308 on breast
      cancer survival, with the per-allele HR for interaction 2.16 (95% CI, 1.30-3.60;
      Pinteraction = 0.003) and HR = 7.77 (95% CI, 0.93-64.71) for the homozygous
      genotype carriers. A biologic rationale is suggested by in silico functional
      analyses. CONCLUSIONS: Our findings suggest carrying the rs8113308 rare allele
      may identify patients who will not benefit from adjuvant endocrine treatment.

PMID- 25964296
TI  - Ofatumumab Exhibits Enhanced In Vitro and In Vivo Activity Compared to Rituximab
      in Preclinical Models of Mantle Cell Lymphoma.
AB  - PURPOSE: Mantle cell lymphoma (MCL) is a mature B-cell lymphoma considered to be
      incurable with current treatments, including first-line rituximab in combination
      with multiagent chemotherapy and for those eligible, high-dose chemotherapy and
      stem cell support or rituximab maintenance. On the other hand, achieving a
      complete remission by high-sensitive flow cytometry is associated with prolonged
      duration of remission, stressing the need to develop and/or incorporate novel
      agents into the management of MCL. To this end, we examined the activity of
      ofatumumab, an anti-CD20 monoclonal antibody with distinct binding and
      immunologic properties compared to rituximab, in MCL preclinical models.
      EXPERIMENTAL DESIGN: MCL cells were labeled with (51)Cr before incubation with
      rituximab or ofatumumab (10 MUg/mL) plus human serum or effector cells. (51)Cr
      release was measured and the percentage of lysis was calculated. Surface CD20,
      CD55, and CD59 were measured by Imagestream analysis. SCID mice inoculated
      subcutaneously with Z138 cells were assigned to control versus four doses of
      ofatumumab or rituximab (10 mg/kg/dose). RESULTS: Ofatumumab exhibited enhanced
      in vitro complement-dependent cytotoxicity activity compared with rituximab in
      MCL cell lines, despite a high degree of in vitro resistance to rituximab
      associated with low CD20 levels and/or high expression of complement inhibitory
      proteins. Ofatumumab also delayed tumor progression and prolonged survival in a
      murine model of MCL. CONCLUSIONS: Our results demonstrate that ofatumumab is more
      effective than rituximab in MCL preclinical models, including in the presence of
      rituximab resistance, and support the clinical investigation of ofatumumab in
      combination with standard systemic chemotherapy in MCL (NCT01527149).

PMID- 25964298
TI  - RNA-Redesign: a web server for fixed-backbone 3D design of RNA.
AB  - RNA is rising in importance as a design medium for interrogating fundamental
      biology and for developing therapeutic and bioengineering applications. While
      there are several online servers for design of RNA secondary structure, there are
      no tools available for the rational design of 3D RNA structure. Here we present
      RNA-Redesign (http://rnaredesign.stanford.edu), an online 3D design tool for RNA.
      This resource utilizes fixed-backbone design to optimize the sequence identity
      and nucleobase conformations of an RNA to match a desired backbone, analogous to
      fundamental tools that underlie rational protein engineering. The resulting
      sequences suggest thermostabilizing mutations that can be experimentally
      verified. Further, sequence preferences that differ between natural and
      computationally designed sequences can suggest whether natural sequences possess
      functional constraints besides folding stability, such as cofactor binding or
      conformational switching. Finally, for biochemical studies, the designed
      sequences can suggest experimental tests of 3D models, including concomitant
      mutation of base triples. In addition to the designs generated, detailed
      graphical analysis is presented through an integrated and user-friendly
      environment. 

PMID- 25964297
TI  - The Allelic Context of the C797S Mutation Acquired upon Treatment with Third
      Generation EGFR Inhibitors Impacts Sensitivity to Subsequent Treatment
      Strategies.
AB  - PURPOSE: A secondary EGFR mutation, T790M, is the most common resistance
      mechanism in EGFR-mutant adenocarcinomas that have progressed on erlotinib. Third
      generation EGFR inhibitors capable of inhibiting mutant EGFR with T790M produce
      responses in nearly two thirds of patients. However, acquired resistance
      mechanisms in patients treated with these drugs are yet to be described.
      EXPERIMENTAL DESIGN: To study acquired resistance to third-generation EGFR
      inhibitors, T790M-positive cells derived from an erlotinib-resistant cancer were
      made resistant to a third-generation TKI and then characterized using cell and
      molecular analyses. RESULTS: Cells resistant to a third-generation TKI acquired
      an additional EGFR mutation, C797S, which prevented suppression of EGFR. Our
      results demonstrate that the allelic context in which C797S was acquired may
      predict responsiveness to alternative treatments. If the C797S and T790M
      mutations are in trans, cells will be resistant to third-generation EGFR TKIs,
      but will be sensitive to a combination of first- and third-generation TKIs. If
      the mutations are in cis, no EGFR TKIs alone or in combination can suppress
      activity. If C797S develops in cells wild-type for T790 (when third-generation
      TKIs are administered in the first-line setting), the cells are resistant to
      third-generation TKIs, but retain sensitivity to first-generation TKIs.
      CONCLUSIONS: Mutation of C797S in EGFR is a novel mechanism of acquired
      resistance to third-generation TKIs. The context in which the C797S develops with
      respect to the other EGFR alleles affects the efficacy of subsequent treatments.

PMID- 25964299
TI  - CATH FunFHMMer web server: protein functional annotations using functional family
      assignments.
AB  - The widening function annotation gap in protein databases and the increasing
      number and diversity of the proteins being sequenced presents new challenges to
      protein function prediction methods. Multidomain proteins complicate the protein
      sequence-structure-function relationship further as new combinations of domains
      can expand the functional repertoire, creating new proteins and functions. Here,
      we present the FunFHMMer web server, which provides Gene Ontology (GO)
      annotations for query protein sequences based on the functional classification of
      the domain-based CATH-Gene3D resource. Our server also provides valuable
      information for the prediction of functional sites. The predictive power of
      FunFHMMer has been validated on a set of 95 proteins where FunFHMMer performs
      better than BLAST, Pfam and CDD. Recent validation by an independent
      international competition ranks FunFHMMer as one of the top function prediction
      methods in predicting GO annotations for both the Biological Process and
      Molecular Function Ontology. The FunFHMMer web server is available at
      http://www.cathdb.info/search/by_funfhmmer. 

PMID- 25964300
TI  - mRNA transfection of a novel TAL effector nuclease (TALEN) facilitates efficient
      knockout of HIV co-receptor CCR5.
AB  - Homozygosity for a natural deletion variant of the HIV-coreceptor molecule CCR5,
      CCR5Delta32, confers resistance toward HIV infection. Allogeneic stem cell
      transplantation from a CCR5Delta32-homozygous donor has resulted in the first
      cure from HIV ('Berlin patient'). Based thereon, genetic disruption of CCR5 using
      designer nucleases was proposed as a promising HIV gene-therapy approach. Here we
      introduce a novel TAL-effector nuclease, CCR5-Uco-TALEN that can be efficiently
      delivered into T cells by mRNA electroporation, a gentle and truly transient gene
      transfer technique. CCR5-Uco-TALEN mediated high-rate CCR5 knockout (>90% in PM1
      and >50% in primary T cells) combined with low off-target activity, as assessed
      by flow cytometry, next-generation sequencing and a newly devised, very
      convenient gene-editing frequency digital-PCR (GEF-dPCR). GEF-dPCR facilitates
      simultaneous detection of wild-type and gene-edited alleles with remarkable
      sensitivity and accuracy as shown for the CCR5 on-target and CCR2 off-target
      loci. CCR5-edited cells were protected from infection with HIV-derived lentiviral
      vectors, but also with the wild-type CCR5-tropic HIV-1BaL strain. Long-term
      exposure to HIV-1BaL resulted in almost complete suppression of viral replication
      and selection of CCR5-gene edited T cells. In conclusion, we have developed a
      novel TALEN for the targeted, high-efficiency knockout of CCR5 and a useful dPCR
      based gene-editing detection method. 

PMID- 25964301
TI  - OrthoVenn: a web server for genome wide comparison and annotation of orthologous
      clusters across multiple species.
AB  - Genome wide analysis of orthologous clusters is an important component of
      comparative genomics studies. Identifying the overlap among orthologous clusters
      can enable us to elucidate the function and evolution of proteins across multiple
      species. Here, we report a web platform named OrthoVenn that is useful for genome
      wide comparisons and visualization of orthologous clusters. OrthoVenn provides
      coverage of vertebrates, metazoa, protists, fungi, plants and bacteria for the
      comparison of orthologous clusters and also supports uploading of customized
      protein sequences from user-defined species. An interactive Venn diagram, summary
      counts, and functional summaries of the disjunction and intersection of clusters
      shared between species are displayed as part of the OrthoVenn result. OrthoVenn
      also includes in-depth views of the clusters using various sequence analysis
      tools. Furthermore, OrthoVenn identifies orthologous clusters of single copy
      genes and allows for a customized search of clusters of specific genes through
      key words or BLAST. OrthoVenn is an efficient and user-friendly web server freely
      accessible at http://probes.pw.usda.gov/OrthoVenn or
      http://aegilops.wheat.ucdavis.edu/OrthoVenn. 

PMID- 25964302
TI  - Aristolochia clematitis, the herb responsible for aristolochic acid nephropathy,
      in an uncultivated piece of land of an Italian nephrologist.
AB  - BACKGROUND: Aristolochia clematitis (AC), a herbaceous plant that belongs to the
      family of Aristolochiaceae, is today considered as being responsible for Balkan
      endemic nephropathy (BEN). Very scarce information is available in the medical
      literature about the presence of AC outside Balkan area. This article reports on
      the finding of AC in Northwest Italy and the results of a questionnaire delivered
      to locals on their knowledge about AC. METHODS: AC was found in an uncultivated
      piece of land of a hilly area of Northwest Italy. It was identified by matching
      it with images available in the literature and Internet. The questionnaire, which
      was delivered with a set of 12 photographs and a bunch of true AC, contained 15
      questions aimed at collecting information on the knowledge of the respondents
      about the existence, name, distribution and possible uses of AC. RESULTS: A total
      of 23 locals, mostly farmers, were interviewed. Among them, 22 (95.6%) had
      already seen AC, mostly in uncultivated areas; 4 (18%) had a name for it; 21
      (95.4%) considered it as a weed and denied any personal use of it; 18 (81.8%)
      stated that breeding animals disliked AC and no one was aware that AC might
      damage kidneys. CONCLUSIONS: This study demonstrates that AC can be found outside
      the Balkan region and that people know it but today do not make any use of it.
      Other studies carried out by nephrologists in other geographic areas could expand
      our knowledge about AC outside the basin of BEN.

PMID- 25964303
TI  - Nucleic Acid surveillance and malaria elimination.

PMID- 25964304
TI  - Capture and Ligation Probe-PCR (CLIP-PCR) for Molecular Screening, with
      Application to Active Malaria Surveillance for Elimination.
AB  - BACKGROUND: Malaria control programs have achieved remarkable success during the
      past decade. Nonetheless, sensitive and affordable methods for active screening
      of malaria parasites in low-transmission settings remain urgently needed.
      METHODS: We developed a molecular screening method, capture and ligation probe
      PCR (CLIP-PCR), which achieved the sensitivity of reverse-transcription PCR but
      eliminated the reliance on RNA purification and reverse transcription. In this
      method, 18S rRNA of genus Plasmodium is released from blood, captured onto 96
      well plates, and quantified by the amount of ligated probes that bind
      continuously to it. We first used laboratory-prepared samples to test the method
      across a range of parasite densities and pool sizes, then applied the method to
      an active screening of 3358 dried blood spot samples collected from 3 low-endemic
      areas in China. RESULTS: Plasmodium falciparum diluted in whole blood lysate
      could be detected at a concentration as low as 0.01 parasites/MUL, and a pool
      size of <=36 did not significantly affect assay performance. When coupled with a
      matrix pooling strategy, the assay drastically increased throughput to thousands
      of samples per run while reducing the assay cost to cents per sample. In the
      active screening, CLIP-PCR identified 14 infections, including 4 asymptomatic
      ones, with <500 tests, costing <US$0.60 for each sample. All positive results
      were confirmed by standard quantitative PCR. CONCLUSIONS: CLIP-PCR, by use of
      dried blood spots with a pooling strategy, efficiently offers a highly sensitive
      and high-throughput approach to detect asymptomatic submicroscopic infections
      with reduced cost and labor, making it an ideal tool for large-scale malaria
      surveillance in elimination settings.

PMID- 25964305
TI  - Reflex Human Papillomavirus Test Results as an Option for the Management of
      Korean Women With Atypical Squamous Cells Cannot Exclude High-Grade Squamous
      Intraepithelial Lesion.
AB  - BACKGROUND: Current guidelines recommend initial colposcopy with biopsy
      regardless of human papillomavirus (HPV) test results in women with atypical
      squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC
      H). The purpose of this study was to evaluate the value of HPV testing in women
      with ASC-H based on colposcopic pathology results. MATERIALS AND METHODS: A
      multicenter cross-sectional study was carried out at three academic hospitals and
      involved 40,847 Korean women who underwent cervical cancer screening with
      cytology and HPV tests with or without subsequent colposcopic biopsies between
      January 2007 and December 2013. RESULTS: ASC-H was diagnosed in 276 women (0.7%).
      Only 6 of 68 (8.8%) women with ASC-H who were HPV negative had cervical
      intraepithelial neoplasia grade >=2 (CIN >=2) lesions, whereas 47.4% of the women
      with ASC-H who were HPV positive had CIN >=2 lesions. No cases of invasive
      cervical cancer were diagnosed among women with ASC-H who were HPV negative.
      Logistic regression analysis was performed using the group with normal
      Papanicolaou test results and HPV-negative status as the reference group. Women
      with ASC-H who were HPV positive had a significantly increased risk of CIN >=2
      lesions, whereas no significant increase was observed in patients with ASC-H and
      HPV-negative status. CONCLUSION: If the result of the HPV test was negative, the
      risk of CIN >=2 lesions in Korean women with ASC-H cytology was low. Reflex HPV
      testing should be an option for the management of women with cytology showing ASC
      H to decrease unnecessary colposcopic biopsies, which are expensive and invasive.
      IMPLICATIONS FOR PRACTICE: Current American Society for Colposcopy and Cervical
      Pathology guidelines recommend universal colposcopy for the management of women
      with atypical squamous cells, cannot exclude high-grade squamous intraepithelial
      lesion (ASC-H) on cytology, regardless of human papillomavirus (HPV) test
      results. The present study suggested that HPV cotesting in patients with ASC-H
      cytology can provide more detailed and useful information regarding the risk of
      high-grade cervical intraepithelial neoplasia (CIN) lesions and the need for
      further treatment. When the result of the HPV test was negative, the risk of CIN
      lesions of grade >=2 in women with ASC-H cytology was low. Consequently, reflex
      HPV testing, rather than immediately performance of invasive and expensive
      colposcopy with biopsy, should be an option for the management of women with ASC
      H.

PMID- 25964306
TI  - Choice of Starting Dose for Biopharmaceuticals in First-in-Human Phase I Cancer
      Clinical Trials.
AB  - BACKGROUND: First-in-human (FIH) trials of low-molecular-weight anticancer agents
      conventionally derive a safe start dose (SD) from one-tenth the severely toxic
      dose in 10% of rodents or one-sixth the highest nonseverely toxic dose (HNSTD) in
      nonrodent species. No consensus has been reached on whether this paradigm can be
      safely applied to biotechnology-derived products (BDPs). MATERIALS AND METHODS: A
      comprehensive search was conducted to identify all BDPs (excluding immune
      checkpoint inhibitors and antibody drug conjugates) with sufficient nonclinical
      and clinical data to assess the safety of hypothetical use of one-sixth HNSTD in
      an advanced cancer FIH trial. RESULTS: The search identified 23 BDPs, of which 21
      were monoclonal antibodies. The median ratio of the maximum tolerated or maximum
      administered dose (MTD or MAD) to the actual FIH SD was 36 (range, 8-500). Only 2
      BDPs reached the MTD. Hypothetical use of one-sixth HNSTD (allometrically scaled
      to humans) would not have exceeded the MTD or MAD for all 23 BDPs and would have
      reduced the median ratio of the MTD or MAD to a SD to 6.1 (range, 3.5-55.3).
      Pharmacodynamic (PD) markers were included in some animal toxicology studies and
      were useful to confirm the hypothetical SD of one-sixth HNSTD. CONCLUSION: One
      sixth HNSTD would not have resulted in unacceptable toxicities in the data
      available. Supporting its use could reduce the number of dose escalations needed
      to reach the recommended dose. A low incidence of toxicities in animals and
      humans underscores the need to identify the pharmacokinetic and PD parameters to
      guide SD selection of BDPs for FIH cancer trials. IMPLICATIONS FOR PRACTICE:
      Start dose (SD) for biotechnology-derived products (BDPs) can be safely derived
      from one-sixth the highest nonseverely toxic dose in nonrodent species and may
      reduce the number of dose escalations needed to reach the recommended dose in
      first-in-human studies while limiting unnecessary exposure to high drug levels in
      humans. The use of this type of SD could improve the design of phase I studies of
      BDPs by making them more efficient. The role of preclinical pharmacodynamic
      markers was useful in confirming the hypothetical SD, and attempts should be
      explored in future animal studies to identify such parameters.

PMID- 25964307
TI  - Clinical Activity of Ipilimumab in Acral Melanoma: A Retrospective Review.
AB  - BACKGROUND: Ipilimumab improves overall survival (OS) in advanced melanoma. Acral
      melanoma is an uncommon clinical subtype of this disease associated with poor
      prognosis. The clinical activity of ipilimumab has not been well-defined in
      advanced acral melanoma. METHODS: We retrospectively reviewed the demographics,
      treatment history, and clinical outcomes for all patients with acral melanoma
      treated with ipilimumab from two academic centers between February 2006 and June
      2013. Using Cox proportional hazards models, we assessed for factors that
      correlated with OS. RESULTS: A total of 35 patients with acral melanoma received
      ipilimumab. Melanomas arose on volar surfaces (n = 28) and subungual sites (n =
      7); stage M1c disease was present in 54%, and 45% had elevated serum lactate
      dehydrogenase (LDH). Best response by RECIST 1.1 criteria was complete response
      in 1 patient, partial response in 3, and stable disease (SD) in 4 for an
      objective response rate (ORR) of 11.4% and a clinical benefit rate (ORR + SD) at
      24 weeks of 22.9%. Median progression-free survival was 2.5 months (95%
      confidence interval [CI]: 2.3-2.7 months); median OS was 16.7 months (95% CI:
      10.9-22.5 months). Normal LDH and absolute lymphocyte count >=1,000 at 7 weeks
      predicted longer OS. Immune-related adverse events (irAEs) were noted in 16
      patients including 7 with grade 3/4 irAEs (20%). CONCLUSION: Ipilimumab is
      clinically active in acral melanoma with similar ORR and OS compared with
      unselected melanoma populations. Ipilimumab remains a viable therapeutic option
      for patients with advanced acral melanoma. IMPLICATIONS FOR PRACTICE: Ipilimumab
      is a commonly used immune therapy that improves survival in metastatic melanoma.
      The clinical activity of ipilimumab in certain rare melanoma subtypes, such as
      uveal or mucosal melanomas, is suboptimal. Acral melanoma is another unusual
      subtype of this disease that arises on the palms, soles, and nailbeds. In this
      study of 35 patients with acral melanoma from 2 centers, ipilimumab was found to
      have activity that appears equivalent to unselected melanoma (response rate of
      11.4%, median overall survival of 16.7 months). Ipilimumab remains a viable
      treatment option for this melanoma subpopulation.

PMID- 25964308
TI  - GFR in Patients with beta-Thalassemia Major.
AB  - BACKGROUND AND OBJECTIVES: Patients with beta-thalassemia major (TM) may have
      tubular dysfunction and glomerular dysfunction, primarily hyperfiltration, based
      on eGFR. Assessment of GFR based on serum creatinine concentration may
      overestimate GFR in these patients. This study sought to determine GFR by using
      inulin clearance and compare it with measured creatinine clearance (Ccr) and
      eGFR. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: Patients followed up in an
      Israeli thalassemia clinic who had been regularly transfused for years and
      treated with deferasirox were included in the study. They were studied by inulin
      clearance, Ccr, the CKD Epidemiology Collaboration and the Modification of Diet
      in Renal Disease equations for eGFR, and the Cockcroft-Gault estimation for Ccr.
      Expected creatinine excretion rate and tubular creatinine secretion rate were
      calculated. RESULTS: Nine white patients were studied. Results, given as medians,
      were as follows: serum creatinine was 0.59 mg/dl (below normal limits); GFR was
      low (76.6 ml/min per 1.73 m(2)) and reached the level of CKD; Ccr was 134.9
      ml/min per 1.73 m(2), higher than the GFR because of a tubular creatinine
      secretion rate of 30.3 ml/min per 1.73 m(2) (this accounted for 40% of the Ccr);
      and eGFR calculated by the CKD Epidemiology Collaboration and Modification of
      Diet in Renal Disease equations and Cockcroft-Gault-estimated Ccr were 133, 141,
      and 168 ml/min per 1.73 m(2), respectively. These latter values were
      significantly higher than the GFR, reaching the hyperfiltration range, and
      indicated that the estimation techniques were clinically unacceptable as a method
      for measuring kidney function compared with the GFR according to Bland and Altman
      analyses. CONCLUSIONS: Contrary to previous reports, patients in this study with
      TM had normal or reduced GFR. The estimating methods showed erroneous
      overestimation of GFR and were clinically unacceptable for GFR measurements in
      patients with TM by Bland and Altman analysis. Therefore, more accurate methods
      should be used for early detection of reduced GFR and prevention of its further
      decline toward CKD in these patients.

PMID- 25964310
TI  - Randomized Controlled Trial of Individualized Dialysate Cooling for Cardiac
      Protection in Hemodialysis Patients.
AB  - BACKGROUND AND OBJECTIVES: Cardiovascular disease is the most common cause of
      death in patients on hemodialysis (HD). HD-associated cardiomyopathy is
      appreciated to be driven by exposure to recurrent and cumulative ischemic insults
      resulting from hemodynamic instability of conventionally performed intermittent
      HD treatment itself. Cooled dialysate reduces HD-induced recurrent ischemic
      injury, but whether this confers long-term protection of the heart in terms of
      cardiac structure and function is not known. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Between September 2009 and January 2013, 73 incident HD patients
      were randomly assigned to a dialysate temperature of 37 degrees C (control) or
      individualized cooling at 0.5 degrees C below body temperature (intervention) for
      12 months. Cardiac structure, function, and aortic distensibility were assessed
      by cardiac magnetic resonance imaging. Mean between-group difference in delivered
      dialysate temperature was 1.2 degrees C+/-0.3 degrees C. Treatment effects were
      determined by the interaction of treatment group with time in linear mixed
      models. RESULTS: There was no between-group difference in the primary outcome of
      left ventricular ejection fraction (1.5%; 95% confidence interval, -4.3% to
      7.3%). However, left ventricular function assessed by peak systolic strain was
      preserved by the intervention (-3.3%; 95% confidence interval, -6.5% to -0.2%) as
      was diastolic function (measured as peak diastolic strain rate, 0.18 s(-1); 95%
      confidence interval, 0.02 to 0.34 s(-1)). Reduction of left ventricular dilation
      was demonstrated by significant reduction in left ventricular end-diastolic
      volume (-23.8 ml; 95% confidence interval, -44.7 to -2.9 ml). The intervention
      was associated with reduced left ventricular mass (-15.6 g; 95% confidence
      interval, -29.4 to -1.9 g). Aortic distensibility was preserved in the
      intervention group (1.8 mmHg(-1)*10(-3); 95% confidence interval, 0.1 to 3.6
      mmHg(-1)*10(-3)). There were no intervention-related withdrawals or adverse
      events. CONCLUSIONS: In patients new to HD, individualized cooled dialysate did
      not alter the primary outcome but was well tolerated and slowed the progression
      of HD-associated cardiomyopathy. Because cooler dialysate is universally
      applicable at no cost, the intervention warrants wider adoption or confirmation
      of these findings in a larger trial.

PMID- 25964311
TI  - Programmed death ligand 1 (PD-L1) as an immunotherapy target in patients with
      glioblastoma.

PMID- 25964309
TI  - Clinical and genetic analysis of patients with cystinuria in the United Kingdom.
AB  - BACKGROUND AND OBJECTIVES: Cystinuria is a rare inherited renal stone disease.
      Mutations in the amino acid exchanger System b(0,+), the two subunits of which
      are encoded by SLC3A1 and SLC7A9, predominantly underlie this disease. The work
      analyzed the epidemiology of cystinuria and the influence of mutations in these
      two genes on disease severity in a United Kingdom cohort. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: Prevalent patients were studied from 2012 to 2014
      in the northeast and southwest of the United Kingdom. Clinical phenotypes were
      defined, and genetic analysis of SLC3A1 and SLC7A9 combining Sanger sequencing
      and multiplex ligation probe-dependent amplification was performed. RESULTS: In
      total, 76 patients (42 men and 34 women) were studied. All subjects had proven
      cystine stones. Median age of presentation (first stone episode) was 24 years
      old, but 21% of patients presented after 40 years old. Patients had varied
      clinical courses, with 37% of patients having >=10 stone episodes; 70% had
      evidence of CKD, and 9% had reached ESRD as a result of cystinuria and its
      complications. Patients with cystinuria received a variety of different
      therapies, with no obvious treatment consensus. Notably, 20% of patients had
      staghorn calculi, with associated impaired renal function in 80% of these
      patients. Genetic analysis revealed that biallelic mutations were present in
      either SLC3A1 (n=27) or SLC7A9 (n=20); 22 patients had only one mutated allele
      detected (SLC3A1 in five patients and SLC7A9 in 17 patients). In total, 37
      different mutant variant alleles were identified, including 12 novel mutations;
      22% of mutations were caused by large gene rearrangements. No genotype-phenotype
      association was detected in this cohort. CONCLUSIONS: Patients with cystinuria in
      the United Kingdom often present atypically with staghorn calculi at >=40 years
      old and commonly develop significant renal impairment. There is no association of
      clinical course with genotype. Treatments directed toward reducing stone burden
      need to be rationalized and developed to optimize patient care.

PMID- 25964312
TI  - Dasatinib in recurrent glioblastoma: failure as a teacher.

PMID- 25964313
TI  - Immunotherapy for glioblastoma: are we finally getting closer?

PMID- 25964314
TI  - Comprehensive respiratory assessment in advanced COPD: a 'campus to clinic'
      translational framework.

PMID- 25964316
TI  - Corrigendum to 'Coping profiles, perceived stress and health-related behaviors: a
      cluster analysis approach'.

PMID- 25964315
TI  - Streptococcus pneumoniae triggers progression of pulmonary fibrosis through
      pneumolysin.
AB  - RATIONALE: Respiratory tract infections are common in patients suffering from
      pulmonary fibrosis. The interplay between bacterial infection and fibrosis is
      characterised poorly. OBJECTIVES: To assess the effect of Gram-positive bacterial
      infection on fibrosis exacerbation in mice. METHODS: Fibrosis progression in
      response to Streptococcus pneumoniae was examined in two different mouse models
      of pulmonary fibrosis. MEASUREMENTS AND MAIN RESULTS: We demonstrate that wild
      type mice exposed to adenoviral vector delivery of active transforming growth
      factor-beta1 (TGFbeta1) or diphteria toxin (DT) treatment of transgenic mice
      expressing the DT receptor (DTR) under control of the surfactant protein C (SPC)
      promoter (SPC-DTR) to induce pulmonary fibrosis developed progressive fibrosis
      following infection with Spn, without exhibiting impaired lung protective
      immunity against Spn. Antibiotic treatment abolished infection-induced fibrosis
      progression. The cytotoxin pneumolysin (Ply) of Spn caused this phenomenon in a
      TLR4-independent manner, as Spn lacking Ply (SpnDeltaply) failed to trigger
      progressive fibrogenesis, whereas purified recombinant Ply did. Progressive
      fibrogenesis was also observed in AdTGFbeta1-exposed Ply-challenged TLR4 KO mice.
      Increased apoptotic cell death of alveolar epithelial cells along with an
      attenuated intrapulmonary release of antifibrogenic prostaglandin E2 was found to
      underlie progressive fibrogenesis in Ply-challenged AdTGFbeta1-exposed mice.
      Importantly, vaccination of mice with the non-cytotoxic Ply derivative B (PdB)
      substantially attenuated Ply-induced progression of lung fibrosis in AdTGFbeta1
      exposed mice. CONCLUSIONS: Our data unravel a novel mechanism by which infection
      with Spn through Ply release induces progression of established lung fibrosis,
      which can be attenuated by protein-based vaccination of mice.

PMID- 25964318
TI  - Prolonged daily light exposure increases body fat mass through attenuation of
      brown adipose tissue activity.
AB  - Disruption of circadian rhythmicity is associated with obesity and related
      disorders, including type 2 diabetes and cardiovascular disease. Specifically,
      prolonged artificial light exposure associates with obesity in humans, although
      the underlying mechanism is unclear. Here, we report that increasing the daily
      hours of light exposure increases body adiposity through attenuation of brown
      adipose tissue (BAT) activity, a major contributor of energy expenditure. Mice
      exposed to a prolonged day length of 16- and 24-h light, compared with regular 12
      h light, showed increased adiposity without affecting food intake or locomotor
      activity. Mechanistically, we demonstrated that prolonged day length decreases
      sympathetic input into BAT and reduces beta3-adrenergic intracellular signaling.
      Concomitantly, prolonging day length decreased the uptake of fatty acids from
      triglyceride-rich lipoproteins, as well as of glucose from plasma selectively by
      BAT. We conclude that impaired BAT activity is an important mediator in the
      association between disturbed circadian rhythm and adiposity, and anticipate that
      activation of BAT may overcome the adverse metabolic consequences of disturbed
      circadian rhythmicity. 

PMID- 25964319
TI  - Reconstructing the neuronal milieu interieur.

PMID- 25964321
TI  - Thermodynamics of formation of coffinite, USiO4.
AB  - Coffinite, USiO4, is an important U(IV) mineral, but its thermodynamic properties
      are not well-constrained. In this work, two different coffinite samples were
      synthesized under hydrothermal conditions and purified from a mixture of
      products. The enthalpy of formation was obtained by high-temperature oxide melt
      solution calorimetry. Coffinite is energetically metastable with respect to a
      mixture of UO2 (uraninite) and SiO2 (quartz) by 25.6 +/- 3.9 kJ/mol. Its standard
      enthalpy of formation from the elements at 25  degrees C is -1,970.0 +/- 4.2
      kJ/mol. Decomposition of the two samples was characterized by X-ray diffraction
      and by thermogravimetry and differential scanning calorimetry coupled with mass
      spectrometric analysis of evolved gases. Coffinite slowly decomposes to U3O8 and
      SiO2 starting around 450  degrees C in air and thus has poor thermal stability in
      the ambient environment. The energetic metastability explains why coffinite
      cannot be synthesized directly from uraninite and quartz but can be made by low
      temperature precipitation in aqueous and hydrothermal environments. These
      thermochemical constraints are in accord with observations of the occurrence of
      coffinite in nature and are relevant to spent nuclear fuel corrosion. 

PMID- 25964320
TI  - GIRK3 gates activation of the mesolimbic dopaminergic pathway by ethanol.
AB  - G protein-gated inwardly rectifying potassium (GIRK) channels are critical
      regulators of neuronal excitability and can be directly activated by ethanol.
      Constitutive deletion of the GIRK3 subunit has minimal phenotypic consequences,
      except in response to drugs of abuse. Here we investigated how the GIRK3 subunit
      contributes to the cellular and behavioral effects of ethanol, as well as to
      voluntary ethanol consumption. We found that constitutive deletion of GIRK3 in
      knockout (KO) mice selectively increased ethanol binge-like drinking, without
      affecting ethanol metabolism, sensitivity to ethanol intoxication, or continuous
      access drinking. Virally mediated expression of GIRK3 in the ventral tegmental
      area (VTA) reversed the phenotype of GIRK3 KO mice and further decreased the
      intake of their wild-type counterparts. In addition, GIRK3 KO mice showed a
      blunted response of the mesolimbic dopaminergic (DA) pathway to ethanol, as
      assessed by ethanol-induced excitation of VTA neurons and DA release in the
      nucleus accumbens. These findings support the notion that the subunit composition
      of VTA GIRK channels is a critical determinant of DA neuron sensitivity to drugs
      of abuse. Furthermore, our study reveals the behavioral impact of this cellular
      effect, whereby the level of GIRK3 expression in the VTA tunes ethanol intake
      under binge-type conditions: the more GIRK3, the less ethanol drinking. 

PMID- 25964322
TI  - Protein aggregation in salt solutions.
AB  - Protein aggregation is broadly important in diseases and in formulations of
      biological drugs. Here, we develop a theoretical model for reversible protein
      protein aggregation in salt solutions. We treat proteins as hard spheres having
      square-well-energy binding sites, using Wertheim's thermodynamic perturbation
      theory. The necessary condition required for such modeling to be realistic is
      that proteins in solution during the experiment remain in their compact form.
      Within this limitation our model gives accurate liquid-liquid coexistence curves
      for lysozyme and gamma IIIa-crystallin solutions in respective buffers. It
      provides good fits to the cloud-point curves of lysozyme in buffer-salt mixtures
      as a function of the type and concentration of salt. It than predicts full
      coexistence curves, osmotic compressibilities, and second virial coefficients
      under such conditions. This treatment may also be relevant to protein
      crystallization.

PMID- 25964323
TI  - Effect of warming temperatures on US wheat yields.
AB  - Climate change is expected to increase future temperatures, potentially resulting
      in reduced crop production in many key production regions. Research quantifying
      the complex relationship between weather variables and wheat yields is rapidly
      growing, and recent advances have used a variety of model specifications that
      differ in how temperature data are included in the statistical yield equation. A
      unique data set that combines Kansas wheat variety field trial outcomes for 1985
      2013 with location-specific weather data is used to analyze the effect of weather
      on wheat yield using regression analysis. Our results indicate that the effect of
      temperature exposure varies across the September-May growing season. The largest
      drivers of yield loss are freezing temperatures in the Fall and extreme heat
      events in the Spring. We also find that the overall effect of warming on yields
      is negative, even after accounting for the benefits of reduced exposure to
      freezing temperatures. Our analysis indicates that there exists a tradeoff
      between average (mean) yield and ability to resist extreme heat across varieties.
      More-recently released varieties are less able to resist heat than older lines.
      Our results also indicate that warming effects would be partially offset by
      increased rainfall in the Spring. Finally, we find that the method used to
      construct measures of temperature exposure matters for both the predictive
      performance of the regression model and the forecasted warming impacts on yields.

PMID- 25964324
TI  - Minimal genomes of mycoplasma-related endobacteria are plastic and contain host
      derived genes for sustained life within Glomeromycota.
AB  - Arbuscular mycorrhizal fungi (AMF, Glomeromycota) colonize roots of the majority
      of terrestrial plants. They provide essential minerals to their plant hosts and
      receive photosynthates in return. All major lineages of AMF harbor endobacteria
      classified as Mollicutes, and known as mycoplasma-related endobacteria (MRE).
      Except for their substantial intrahost genetic diversity and ability to transmit
      vertically, virtually nothing is known about the life history of these
      endobacteria. To understand MRE biology, we sequenced metagenomes of three MRE
      populations, each associated with divergent AMF hosts. We found that each AMF
      species harbored a genetically distinct group of MRE. Despite vertical
      transmission, all MRE populations showed extensive chromosomal rearrangements,
      which we attributed to genetic recombination, activity of mobile elements, and a
      history of plectroviral invasion. The MRE genomes are characterized by a highly
      reduced gene content, indicating metabolic dependence on the fungal host, with
      the mechanism of energy production remaining unclear. Several MRE genes encode
      proteins with domains involved in protein-protein interactions with eukaryotic
      hosts. In addition, the MRE genomes harbor genes horizontally acquired from AMF.
      Some of these genes encode small ubiquitin-like modifier (SUMO) proteases
      specific to the SUMOylation systems of eukaryotes, which MRE likely use to
      manipulate their fungal host. The extent of MRE genome plasticity and reduction,
      along with the large number of horizontally acquired host genes, suggests a high
      degree of adaptation to the fungal host. These features, together with the
      ubiquity of the MRE-Glomeromycota associations, emphasize the significance of MRE
      in the biology of Glomeromycota. 

PMID- 25964325
TI  - Insights into ParB spreading from the complex structure of Spo0J and parS.
AB  - Spo0J (stage 0 sporulation protein J, a member of the ParB superfamily) is an
      essential component of the ParABS (partition system of ParA, ParB, and parS)
      related bacterial chromosome segregation system. ParB (partition protein B) and
      its regulatory protein, ParA, act cooperatively through parS (partition S) DNA to
      facilitate chromosome segregation. ParB binds to chromosomal DNA at specific parS
      sites as well as the neighboring nonspecific DNA sites. Various ParB molecules
      can associate together and spread along the chromosomal DNA. ParB oligomer and
      parS DNA interact together to form a high-order nucleoprotein that is required
      for the loading of the structural maintenance of chromosomes proteins onto the
      chromosome for chromosomal DNA condensation. In this report, we characterized the
      binding of parS and Spo0J from Helicobacter pylori (HpSpo0J) and solved the
      crystal structure of the C-terminal domain truncated protein (Ct-HpSpo0J)-parS
      complex. Ct-HpSpo0J folds into an elongated structure that includes a flexible N
      terminal domain for protein-protein interaction and a conserved DNA-binding
      domain for parS binding. Two Ct-HpSpo0J molecules bind with one parS. Ct-HpSpo0J
      interacts vertically and horizontally with its neighbors through the N-terminal
      domain to form an oligomer. These adjacent and transverse interactions are
      accomplished via a highly conserved arginine patch: RRLR. These interactions
      might be needed for molecular assembly of a high-order nucleoprotein complex and
      for ParB spreading. A structural model for ParB spreading and chromosomal DNA
      condensation that lead to chromosome segregation is proposed. 

PMID- 25964326
TI  - The rise of oxygen and siderite oxidation during the Lomagundi Event.
AB  - The Paleoproterozoic Lomagundi Event is an interval of 130-250 million years, ca.
      2.3-2.1 billion years ago, in which extraordinarily (13)C enriched (>100/00)
      limestones and dolostones occur globally. The high levels of organic carbon
      burial implied by the positive delta(13)C values suggest the production of vast
      quantities of O2 as well as an alkalinity imbalance demanding extremely low
      levels of weathering. The oxidation of sulfides has been proposed as a mechanism
      capable of ameliorating these imbalances: It is a potent sink for O2 as well as a
      source of acidity. However, sulfide oxidation consumes more O2 than it can supply
      CO2, leading to insurmountable imbalances in both carbon and oxygen. In contrast,
      the oxidation of siderite (FeCO3 proper, as well as other Fe(2+)-bearing
      carbonate minerals), produces 4 times more CO2 than it consumes O2 and is a
      common--although often overlooked--constituent of Archean and Early Proterozoic
      sedimentary successions. Here we propose that following the initial rise of O2 in
      the atmosphere, oxidation of siderite provided the necessary carbon for the
      continued oxidation of sulfides, burial of organic carbon, and, most importantly,
      accumulation of free O2. The duration and magnitude of the Lomagundi Event were
      determined by the size of the preexisting Archean siderite reservoir, which was
      consumed through oxidative weathering. Our proposal helps resolve a long-standing
      conundrum and advances our understanding of the geologic history of atmospheric
      O2.

PMID- 25964328
TI  - Climatic dipoles drive two principal modes of North American boreal bird
      irruption.
AB  - Pine Siskins exemplify normally boreal seed-eating birds that can be sparse or
      absent across entire regions of North America in one year and then appear in
      large numbers the next. These dramatic avian "irruptions" are thought to stem
      from intermittent but broadly synchronous seed production (masting) in one year
      and meager seed crops in the next. A prevalent hypothesis is that widespread
      masting in the boreal forest at high latitudes is driven primarily by favorable
      climate during the two to three consecutive years required to initiate and mature
      seed crops in most conifers. Seed production is expensive for trees and is much
      reduced in the years following masting, driving boreal birds to search elsewhere
      for food and overwintering habitat. Despite this plausible logic, prior efforts
      to discover climate-irruption relationships have been inconclusive. Here,
      analysis of more than 2 million Pine Siskin observations from Project
      FeederWatch, a citizen science program, reveals two principal irruption modes
      (North-South and West-East), both of which are correlated with climate
      variability. The North-South irruption mode is, in part, influenced by winter
      harshness, but the predominant climate drivers of both modes manifest in the warm
      season as continental-scale pairs of oppositely signed precipitation and
      temperature anomalies (i.e., dipoles). The climate dipoles juxtapose favorable
      and unfavorable conditions for seed production and wintering habitat, motivating
      a push-pull paradigm to explain irruptions of Pine Siskins and possibly other
      boreal bird populations in North America. 

PMID- 25964327
TI  - Inositol phosphate pathway controls transcription of telomeric expression sites
      in trypanosomes.
AB  - African trypanosomes evade clearance by host antibodies by periodically changing
      their variant surface glycoprotein (VSG) coat. They transcribe only one VSG gene
      at a time from 1 of about 20 telomeric expression sites (ESs). They undergo
      antigenic variation by switching transcription between telomeric ESs or by
      recombination of the VSG gene expressed. We show that the inositol phosphate (IP)
      pathway controls transcription of telomeric ESs and VSG antigenic switching in
      Trypanosoma brucei. Conditional knockdown of phosphatidylinositol 5-kinase
      (TbPIP5K) or phosphatidylinositol 5-phosphatase (TbPIP5Pase) or overexpression of
      phospholipase C (TbPLC) derepresses numerous silent ESs in T. brucei bloodstream
      forms. The derepression is specific to telomeric ESs, and it coincides with an
      increase in the number of colocalizing telomeric and RNA polymerase I foci in the
      nucleus. Monoallelic VSG transcription resumes after reexpression of TbPIP5K;
      however, most of the resultant cells switched the VSG gene expressed. TbPIP5K,
      TbPLC, their substrates, and products localize to the plasma membrane, whereas
      TbPIP5Pase localizes to the nucleus proximal to telomeres. TbPIP5Pase associates
      with repressor/activator protein 1 (TbRAP1), and their telomeric silencing
      function is altered by TbPIP5K knockdown. These results show that specific steps
      in the IP pathway control ES transcription and antigenic switching in T. brucei
      by epigenetic regulation of telomere silencing. 

PMID- 25964329
TI  - Imaging metabolite dynamics in living cells using a Spinach-based riboswitch.
AB  - Riboswitches are natural ligand-sensing RNAs typically that are found in the 5'
      UTRs of mRNA. Numerous classes of riboswitches have been discovered, enabling
      mRNA to be regulated by diverse and physiologically important cellular
      metabolites and small molecules. Here we describe Spinach riboswitches, a new
      class of genetically encoded metabolite sensor derived from naturally occurring
      riboswitches. Drawing upon the structural switching mechanism of natural
      riboswitches, we show that Spinach can be swapped for the expression platform of
      various riboswitches, allowing metabolite binding to induce Spinach fluorescence
      directly. In the case of the thiamine 5'-pyrophosphate (TPP) riboswitch from the
      Escherichia coli thiM gene encoding hydroxyethylthiazole kinase, we show that
      insertion of Spinach results in an RNA sensor that exhibits fluorescence upon
      binding TPP. This TPP Spinach riboswitch binds TPP with affinity and selectivity
      similar to that of the endogenous riboswitch and enables the discovery of
      agonists and antagonists of the TPP riboswitch using simple fluorescence
      readouts. Furthermore, expression of the TPP Spinach riboswitch in Escherichia
      coli enables live imaging of dynamic changes in intracellular TPP concentrations
      in individual cells. Additionally, we show that other riboswitches that use a
      structural mechanism similar to that of the TPP riboswitch, including the guanine
      and adenine riboswitches from the Bacillus subtilis xpt gene encoding xanthine
      phosphoribosyltransferase, and the S-adenosyl-methionine-I riboswitch from the B.
      subtilis yitJ gene encoding methionine synthase, can be converted into Spinach
      riboswitches. Thus, Spinach riboswitches constitute a novel class of RNA-based
      fluorescent metabolite sensors that exploit the diversity of naturally occurring
      ligand-binding riboswitches. 

PMID- 25964330
TI  - Sigma-1 receptor regulates Tau phosphorylation and axon extension by shaping p35
      turnover via myristic acid.
AB  - Dysregulation of cyclin-dependent kinase 5 (cdk5) per relative concentrations of
      its activators p35 and p25 is implicated in neurodegenerative diseases. P35 has a
      short t1/2 and undergoes rapid proteasomal degradation in its membrane-bound
      myristoylated form. P35 is converted by calpain to p25, which, along with an
      extended t1/2, promotes aberrant activation of cdk5 and causes abnormal
      hyperphosphorylation of tau, thus leading to the formation of neurofibrillary
      tangles. The sigma-1 receptor (Sig-1R) is an endoplasmic reticulum chaperone that
      is implicated in neuronal survival. However, the specific role of the Sig-1R in
      neurodegeneration is unclear. Here we found that Sig-1Rs regulate proper tau
      phosphorylation and axon extension by promoting p35 turnover through the
      receptor's interaction with myristic acid. In Sig-1R-KO neurons, a greater
      accumulation of p35 is seen, which results from neither elevated transcription of
      p35 nor disrupted calpain activity, but rather to the slower degradation of p35.
      In contrast, Sig-1R overexpression causes a decrease of p35. Sig-1R-KO neurons
      exhibit shorter axons with lower densities. Myristic acid is found here to bind
      Sig-1R as an agonist that causes the dissociation of Sig-1R from its cognate
      partner binding immunoglobulin protein. Remarkably, treatment of Sig-1R-KO
      neurons with exogenous myristic acid mitigates p35 accumulation, diminishes tau
      phosphorylation, and restores axon elongation. Our results define the involvement
      of Sig-1Rs in neurodegeneration and provide a mechanistic explanation that Sig
      1Rs help maintain proper tau phosphorylation by potentially carrying and
      providing myristic acid to p35 for enhanced p35 degradation to circumvent the
      formation of overreactive cdk5/p25. 

PMID- 25964331
TI  - Deep-sea hydrothermal vent bacteria related to human pathogenic Vibrio species.
AB  - Vibrio species are both ubiquitous and abundant in marine coastal waters,
      estuaries, ocean sediment, and aquaculture settings worldwide. We report here the
      isolation, characterization, and genome sequence of a novel Vibrio species,
      Vibrio antiquarius, isolated from a mesophilic bacterial community associated
      with hydrothermal vents located along the East Pacific Rise, near the southwest
      coast of Mexico. Genomic and phenotypic analysis revealed V. antiquarius is
      closely related to pathogenic Vibrio species, namely Vibrio alginolyticus, Vibrio
      parahaemolyticus, Vibrio harveyi, and Vibrio vulnificus, but sufficiently
      divergent to warrant a separate species status. The V. antiquarius genome encodes
      genes and operons with ecological functions relevant to the environment
      conditions of the deep sea and also harbors factors known to be involved in human
      disease caused by freshwater, coastal, and brackish water vibrios. The presence
      of virulence factors in this deep-sea Vibrio species suggests a far more
      fundamental role of these factors for their bacterial host. Comparative genomics
      revealed a variety of genomic events that may have provided an important driving
      force in V. antiquarius evolution, facilitating response to environmental
      conditions of the deep sea. 

PMID- 25964332
TI  - Light signaling controls nuclear architecture reorganization during seedling
      establishment.
AB  - The spatial organization of chromatin can be subject to extensive remodeling in
      plant somatic cells in response to developmental and environmental signals.
      However, the mechanisms controlling these dynamic changes and their functional
      impact on nuclear activity are poorly understood. Here, we determined that light
      perception triggers a switch between two different nuclear architectural schemes
      during Arabidopsis postembryonic development. Whereas progressive nucleus
      expansion and heterochromatin rearrangements in cotyledon cells are achieved
      similarly under light and dark conditions during germination, the later steps
      that lead to mature nuclear phenotypes are intimately associated with the
      photomorphogenic transition in an organ-specific manner. The light signaling
      integrators DE-ETIOLATED 1 and CONSTITUTIVE PHOTOMORPHOGENIC 1 maintain
      heterochromatin in a decondensed state in etiolated cotyledons. In contrast,
      under light conditions cryptochrome-mediated photoperception releases nuclear
      expansion and heterochromatin compaction within conspicuous chromocenters. For
      all tested loci, chromatin condensation during photomorphogenesis does not
      detectably rely on DNA methylation-based processes. Notwithstanding, the
      efficiency of transcriptional gene silencing may be impacted during the
      transition, as based on the reactivation of transposable element-driven reporter
      genes. Finally, we report that global engagement of RNA polymerase II in
      transcription is highly increased under light conditions, suggesting that
      cotyledon photomorphogenesis involves a transition from globally quiescent to
      more active transcriptional states. Given these findings, we propose that light
      triggered changes in nuclear architecture underlie interplays between
      heterochromatin reorganization and transcriptional reprogramming associated with
      the establishment of photosynthesis. 

PMID- 25964333
TI  - Body size affects the evolution of eyespots in caterpillars.
AB  - Many caterpillars have conspicuous eye-like markings, called eyespots. Despite
      recent work demonstrating the efficacy of eyespots in deterring predator attack,
      a fundamental question remains: Given their protective benefits, why have
      eyespots not evolved in more caterpillars? Using a phylogenetically controlled
      analysis of hawkmoth caterpillars, we show that eyespots are associated with
      large body size. This relationship could arise because (i) large prey are
      innately conspicuous; (ii) large prey are more profitable, and thus face stronger
      selection to evolve such defenses; and/or (iii) eyespots are more effective on
      large-bodied prey. To evaluate these hypotheses, we exposed small and large
      caterpillar models with and without eyespots in a 2 * 2 factorial design to avian
      predators in the field. Overall, eyespots increased prey mortality, but the
      effect was particularly marked in small prey, and eyespots decreased mortality of
      large prey in some microhabitats. We then exposed artificial prey to naive
      domestic chicks in a laboratory setting following a 2 * 3 design (small or large
      size * no, small, or large eyespots). Predators attacked small prey with eyespots
      more quickly, but were more wary of large caterpillars with large eyespots than
      those without eyespots or with small eyespots. Taken together, these data suggest
      that eyespots are effective deterrents only when both prey and eyespots are
      large, and that innate aversion toward eyespots is conditional. We conclude that
      the distribution of eyespots in nature likely results from selection against
      eyespots in small caterpillars and selection for eyespots in large caterpillars
      (at least in some microhabitats). 

PMID- 25964334
TI  - Immune-checkpoint proteins VISTA and PD-1 nonredundantly regulate murine T-cell
      responses.
AB  - V-domain immunoglobulin suppressor of T-cell activation (VISTA) is a negative
      immune-checkpoint protein that suppresses T-cell responses. To determine whether
      VISTA synergizes with another immune-checkpoint, programmed death 1 (PD-1), this
      study characterizes the immune responses in VISTA-deficient, PD-1-deficient (KO)
      mice and VISTA/PD-1 double KO mice. Chronic inflammation and spontaneous
      activation of T cells were observed in both single KO mice, demonstrating their
      nonredundancy. However, the VISTA/PD-1 double KO mice exhibited significantly
      higher levels of these phenotypes than the single KO mice. When bred onto the 2D2
      T-cell receptor transgenic mice, which are predisposed to development of
      inflammatory autoimmune disease in the CNS, the level of disease penetrance was
      significantly enhanced in the double KO mice compared with in the single KO mice.
      Consistently, the magnitude of T-cell response toward foreign antigens was
      synergistically higher in the VISTA/PD-1 double KO mice. A combinatorial blockade
      using monoclonal antibodies specific for VISTA and PD-L1 achieved optimal tumor
      clearing therapeutic efficacy. In conclusion, our study demonstrates the
      nonredundant role of VISTA that is distinct from the PD-1/PD-L1 pathway in
      controlling T-cell activation. These findings provide the rationale to
      concurrently target VISTA and PD-1 pathways for treating T-cell-regulated
      diseases such as cancer. 

PMID- 25964335
TI  - Mosaic genome of endobacteria in arbuscular mycorrhizal fungi: Transkingdom gene
      transfer in an ancient mycoplasma-fungus association.
AB  - For more than 450 million years, arbuscular mycorrhizal fungi (AMF) have formed
      intimate, mutualistic symbioses with the vast majority of land plants and are
      major drivers in almost all terrestrial ecosystems. The obligate plant-symbiotic
      AMF host additional symbionts, so-called Mollicutes-related endobacteria (MRE).
      To uncover putative functional roles of these widespread but yet enigmatic MRE,
      we sequenced the genome of DhMRE living in the AMF Dentiscutata heterogama.
      Multilocus phylogenetic analyses showed that MRE form a previously unidentified
      lineage sister to the hominis group of Mycoplasma species. DhMRE possesses a
      strongly reduced metabolic capacity with 55% of the proteins having unknown
      function, which reflects unique adaptations to an intracellular lifestyle. We
      found evidence for transkingdom gene transfer between MRE and their AMF host. At
      least 27 annotated DhMRE proteins show similarities to nuclear-encoded proteins
      of the AMF Rhizophagus irregularis, which itself lacks MRE. Nuclear-encoded
      homologs could moreover be identified for another AMF, Gigaspora margarita, and
      surprisingly, also the non-AMF Mortierella verticillata. Our data indicate a
      possible origin of the MRE-fungus association in ancestors of the Glomeromycota
      and Mucoromycotina. The DhMRE genome encodes an arsenal of putative regulatory
      proteins with eukaryotic-like domains, some of them encoded in putative genomic
      islands. MRE are highly interesting candidates to study the evolution and
      interactions between an ancient, obligate endosymbiotic prokaryote with its
      obligate plant-symbiotic fungal host. Our data moreover may be used for further
      targeted searches for ancient effector-like proteins that may be key components
      in the regulation of the arbuscular mycorrhiza symbiosis. 

PMID- 25964336
TI  - Let-7 family of microRNA is required for maturation and adult-like metabolism in
      stem cell-derived cardiomyocytes.
AB  - In metazoans, transition from fetal to adult heart is accompanied by a switch in
      energy metabolism-glycolysis to fatty acid oxidation. The molecular factors
      regulating this metabolic switch remain largely unexplored. We first demonstrate
      that the molecular signatures in 1-year (y) matured human embryonic stem cell
      derived cardiomyocytes (hESC-CMs) are similar to those seen in in vivo-derived
      mature cardiac tissues, thus making them an excellent model to study human
      cardiac maturation. We further show that let-7 is the most highly up-regulated
      microRNA (miRNA) family during in vitro human cardiac maturation. Gain- and loss
      of-function analyses of let-7g in hESC-CMs demonstrate it is both required and
      sufficient for maturation, but not for early differentiation of CMs.
      Overexpression of let-7 family members in hESC-CMs enhances cell size, sarcomere
      length, force of contraction, and respiratory capacity. Interestingly, large
      scale expression data, target analysis, and metabolic flux assays suggest this
      let-7-driven CM maturation could be a result of down-regulation of the
      phosphoinositide 3 kinase (PI3K)/AKT protein kinase/insulin pathway and an up
      regulation of fatty acid metabolism. These results indicate let-7 is an important
      mediator in augmenting metabolic energetics in maturing CMs. Promoting maturation
      of hESC-CMs with let-7 overexpression will be highly significant for basic and
      applied research. 

PMID- 25964337
TI  - A natural experiment of social network formation and dynamics.
AB  - Social networks affect many aspects of life, including the spread of diseases,
      the diffusion of information, the workers' productivity, and consumers' behavior.
      Little is known, however, about how these networks form and change. Estimating
      causal effects and mechanisms that drive social network formation and dynamics is
      challenging because of the complexity of engineering social relations in a
      controlled environment, endogeneity between network structure and individual
      characteristics, and the lack of time-resolved data about individuals' behavior.
      We leverage data from a sample of 1.5 million college students on Facebook, who
      wrote more than 630 million messages and 590 million posts over 4 years, to
      design a long-term natural experiment of friendship formation and social dynamics
      in the aftermath of a natural disaster. The analysis shows that affected
      individuals are more likely to strengthen interactions, while maintaining the
      same number of friends as unaffected individuals. Our findings suggest that the
      formation of social relationships may serve as a coping mechanism to deal with
      high-stress situations and build resilience in communities. 

PMID- 25964338
TI  - Generalized receptor law governs phototaxis in the phytoplankton Euglena
      gracilis.
AB  - Phototaxis, the process through which motile organisms direct their swimming
      toward or away from light, is implicated in key ecological phenomena (including
      algal blooms and diel vertical migration) that shape the distribution, diversity,
      and productivity of phytoplankton and thus energy transfer to higher trophic
      levels in aquatic ecosystems. Phototaxis also finds important applications in
      biofuel reactors and microbiopropellers and is argued to serve as a benchmark for
      the study of biological invasions in heterogeneous environments owing to the ease
      of generating stochastic light fields. Despite its ecological and technological
      relevance, an experimentally tested, general theoretical model of phototaxis
      seems unavailable to date. Here, we present accurate measurements of the behavior
      of the alga Euglena gracilis when exposed to controlled light fields. Analysis of
      E. gracilis' phototactic accumulation dynamics over a broad range of light
      intensities proves that the classic Keller-Segel mathematical framework for taxis
      provides an accurate description of both positive and negative phototaxis only
      when phototactic sensitivity is modeled by a generalized "receptor law," a
      specific nonlinear response function to light intensity that drives algae toward
      beneficial light conditions and away from harmful ones. The proposed phototactic
      model captures the temporal dynamics of both cells' accumulation toward light
      sources and their dispersion upon light cessation. The model could thus be of use
      in integrating models of vertical phytoplankton migrations in marine and
      freshwater ecosystems, and in the design of bioreactors. 

PMID- 25964339
TI  - Correction for Tian et al., Avian influenza H5N1 viral and bird migration
      networks in Asia.

PMID- 25964340
TI  - Infection of phytoplankton by aerosolized marine viruses.
AB  - Marine viruses constitute a major ecological and evolutionary driving force in
      the marine ecosystems. However, their dispersal mechanisms remain underexplored.
      Here we follow the dynamics of Emiliania huxleyi viruses (EhV) that infect the
      ubiquitous, bloom-forming phytoplankton E. huxleyi and show that EhV are emitted
      to the atmosphere as primary marine aerosols. Using a laboratory-based setup, we
      showed that the dynamic of EhV aerial emission is strongly coupled to the host
      virus dynamic in the culture media. In addition, we recovered EhV DNA from
      atmospheric samples collected over an E. huxleyi bloom in the North Atlantic,
      providing evidence for aerosolization of marine viruses in their natural
      environment. Decay rate analysis in the laboratory revealed that aerosolized
      viruses can remain infective under meteorological conditions prevailing during E.
      huxleyi blooms in the ocean, allowing potential dispersal and infectivity over
      hundreds of kilometers. Based on the combined laboratory and in situ findings, we
      propose that atmospheric transport of EhV is an effective transmission mechanism
      for spreading viral infection over large areas in the ocean. This transmission
      mechanism may also have an important ecological impact on the large-scale host
      virus "arms race" during bloom succession and consequently the turnover of carbon
      in the ocean. 

PMID- 25964341
TI  - Identifying personal microbiomes using metagenomic codes.
AB  - Community composition within the human microbiome varies across individuals, but
      it remains unknown if this variation is sufficient to uniquely identify
      individuals within large populations or stable enough to identify them over time.
      We investigated this by developing a hitting set-based coding algorithm and
      applying it to the Human Microbiome Project population. Our approach defined body
      site-specific metagenomic codes: sets of microbial taxa or genes prioritized to
      uniquely and stably identify individuals. Codes capturing strain variation in
      clade-specific marker genes were able to distinguish among 100s of individuals at
      an initial sampling time point. In comparisons with follow-up samples collected
      30-300 d later, ~30% of individuals could still be uniquely pinpointed using
      metagenomic codes from a typical body site; coincidental (false positive) matches
      were rare. Codes based on the gut microbiome were exceptionally stable and
      pinpointed >80% of individuals. The failure of a code to match its owner at a
      later time point was largely explained by the loss of specific microbial strains
      (at current limits of detection) and was only weakly associated with the length
      of the sampling interval. In addition to highlighting patterns of temporal
      variation in the ecology of the human microbiome, this work demonstrates the
      feasibility of microbiome-based identifiability-a result with important ethical
      implications for microbiome study design. The datasets and code used in this work
      are available for download from huttenhower.sph.harvard.edu/idability. 

PMID- 25964342
TI  - Major evolutionary transitions in individuality.
AB  - The evolution of life on earth has been driven by a small number of major
      evolutionary transitions. These transitions have been characterized by
      individuals that could previously replicate independently, cooperating to form a
      new, more complex life form. For example, archaea and eubacteria formed
      eukaryotic cells, and cells formed multicellular organisms. However, not all
      cooperative groups are en route to major transitions. How can we explain why
      major evolutionary transitions have or haven't taken place on different branches
      of the tree of life? We break down major transitions into two steps: the
      formation of a cooperative group and the transformation of that group into an
      integrated entity. We show how these steps require cooperation, division of
      labor, communication, mutual dependence, and negligible within-group conflict. We
      find that certain ecological conditions and the ways in which groups form have
      played recurrent roles in driving multiple transitions. In contrast, we find that
      other factors have played relatively minor roles at many key points, such as
      within-group kin discrimination and mechanisms to actively repress competition.
      More generally, by identifying the small number of factors that have driven major
      transitions, we provide a simpler and more unified description of how life on
      earth has evolved. 

PMID- 25964343
TI  - N-lactoyl-amino acids are ubiquitous metabolites that originate from CNDP2
      mediated reverse proteolysis of lactate and amino acids.
AB  - Despite technological advances in metabolomics, large parts of the human
      metabolome are still unexplored. In an untargeted metabolomics screen aiming to
      identify substrates of the orphan transporter ATP-binding cassette subfamily C
      member 5 (ABCC5), we identified a class of mammalian metabolites, N-lactoyl-amino
      acids. Using parallel protein fractionation in conjunction with shotgun
      proteomics on fractions containing N-lactoyl-Phe-forming activity, we
      unexpectedly found that a protease, cytosolic nonspecific dipeptidase 2 (CNDP2),
      catalyzes their formation. N-lactoyl-amino acids are ubiquitous pseudodipeptides
      of lactic acid and amino acids that are rapidly formed by reverse proteolysis, a
      process previously considered to be negligible in vivo. The plasma levels of
      these metabolites strongly correlate with plasma levels of lactate and amino
      acid, as shown by increased levels after physical exercise and in patients with
      phenylketonuria who suffer from elevated Phe levels. Our approach to identify
      unknown metabolites and their biosynthesis has general applicability in the
      further exploration of the human metabolome. 

PMID- 25964344
TI  - Correction for Barrio et al., In vivo characterization of chronic traumatic
      encephalopathy using [F-18]FDDNP PET brain imaging.

PMID- 25964345
TI  - MYC oncogene overexpression drives renal cell carcinoma in a mouse model through
      glutamine metabolism.
AB  - The MYC oncogene is frequently mutated and overexpressed in human renal cell
      carcinoma (RCC). However, there have been no studies on the causative role of MYC
      or any other oncogene in the initiation or maintenance of kidney tumorigenesis.
      Here, we show through a conditional transgenic mouse model that the MYC oncogene,
      but not the RAS oncogene, initiates and maintains RCC. Desorption electrospray
      ionization-mass-spectrometric imaging was used to obtain chemical maps of
      metabolites and lipids in the mouse RCC samples. Gene expression analysis
      revealed that the mouse tumors mimicked human RCC. The data suggested that MYC
      induced RCC up-regulated the glutaminolytic pathway instead of the glycolytic
      pathway. The pharmacologic inhibition of glutamine metabolism with bis-2-(5
      phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide impeded MYC-mediated RCC
      tumor progression. Our studies demonstrate that MYC overexpression causes RCC and
      points to the inhibition of glutamine metabolism as a potential therapeutic
      approach for the treatment of this disease. 

PMID- 25964347
TI  - Nonlinearity and chaos in ecological dynamics revisited.

PMID- 25964346
TI  - Elucidation of G-protein and beta-arrestin functional selectivity at the dopamine
      D2 receptor.
AB  - The neuromodulator dopamine signals through the dopamine D2 receptor (D2R) to
      modulate central nervous system functions through diverse signal transduction
      pathways. D2R is a prominent target for drug treatments in disorders where
      dopamine function is aberrant, such as schizophrenia. D2R signals through
      distinct G-protein and beta-arrestin pathways, and drugs that are functionally
      selective for these pathways could have improved therapeutic potential. How D2R
      signals through the two pathways is still not well defined, and efforts to
      elucidate these pathways have been hampered by the lack of adequate tools for
      assessing the contribution of each pathway independently. To address this,
      Evolutionary Trace was used to produce D2R mutants with strongly biased signal
      transduction for either the G-protein or beta-arrestin interactions. These
      mutants were used to resolve the role of G proteins and beta-arrestins in D2R
      signaling assays. The results show that D2R interactions with the two downstream
      effectors are dissociable and that G-protein signaling accounts for D2R canonical
      MAP kinase signaling cascade activation, whereas beta-arrestin only activates
      elements of this cascade under certain conditions. Nevertheless, when expressed
      in mice in GABAergic medium spiny neurons of the striatum, the beta-arrestin
      biased D2R caused a significant potentiation of amphetamine-induced locomotion,
      whereas the G protein-biased D2R had minimal effects. The mutant receptors
      generated here provide a molecular tool set that should enable a better
      definition of the individual roles of G-protein and beta-arrestin signaling
      pathways in D2R pharmacology, neurobiology, and associated pathologies. 

PMID- 25964348
TI  - A tortoise-hare pattern seen in adapting structured and unstructured populations
      suggests a rugged fitness landscape in bacteria.
AB  - In the context of Wright's adaptive landscape, genetic epistasis can yield a
      multipeaked or "rugged" topography. In an unstructured population, a lineage with
      selective access to multiple peaks is expected to fix rapidly on one, which may
      not be the highest peak. In a spatially structured population, on the other hand,
      beneficial mutations take longer to spread. This slowdown allows distant parts of
      the population to explore the landscape semiindependently. Such a population can
      simultaneously discover multiple peaks, and the genotype at the highest
      discovered peak is expected to dominate eventually. Thus, structured populations
      sacrifice initial speed of adaptation for breadth of search. As in the fable of
      the tortoise and the hare, the structured population (tortoise) starts relatively
      slow but eventually surpasses the unstructured population (hare) in average
      fitness. In contrast, on single-peak landscapes that lack epistasis, all uphill
      paths converge. Given such "smooth" topography, breadth of search is devalued and
      a structured population only lags behind an unstructured population in average
      fitness (ultimately converging). Thus, the tortoise-hare pattern is an indicator
      of ruggedness. After verifying these predictions in simulated populations where
      ruggedness is manipulable, we explore average fitness in metapopulations of
      Escherichia coli. Consistent with a rugged landscape topography, we find a
      tortoise-hare pattern. Further, we find that structured populations accumulate
      more mutations, suggesting that distant peaks are higher. This approach can be
      used to unveil landscape topography in other systems, and we discuss its
      application for antibiotic resistance, engineering problems, and elements of
      Wright's shifting balance process. 

PMID- 25964349
TI  - The recent invasion of natural Drosophila simulans populations by the P-element.
AB  - The P-element is one of the best understood eukaryotic transposable elements. It
      invaded Drosophila melanogaster populations within a few decades but was thought
      to be absent from close relatives, including Drosophila simulans. Five decades
      after the spread in D. melanogaster, we provide evidence that the P-element has
      also invaded D. simulans. P-elements in D. simulans appear to have been acquired
      recently from D. melanogaster probably via a single horizontal transfer event.
      Expression data indicate that the P-element is processed in the germ line of D.
      simulans, and genomic data show an enrichment of P-element insertions in putative
      origins of replication, similar to that seen in D. melanogaster. This ongoing
      spread of the P-element in natural populations provides a unique opportunity to
      understand the dynamics of transposable element spread and the associated piwi
      interacting RNAs defense mechanisms. 

PMID- 25964350
TI  - Severity of ocean acidification following the end-Cretaceous asteroid impact.
AB  - Most paleo-episodes of ocean acidification (OA) were either too slow or too small
      to be instructive in predicting near-future impacts. The end-Cretaceous event (66
      Mya) is intriguing in this regard, both because of its rapid onset and also
      because many pelagic calcifying species (including 100% of ammonites and more
      than 90% of calcareous nannoplankton and foraminifera) went extinct at this time.
      Here we evaluate whether extinction-level OA could feasibly have been produced by
      the asteroid impact. Carbon cycle box models were used to estimate OA
      consequences of (i) vaporization of up to 60 * 10(15) mol of sulfur from gypsum
      rocks at the point of impact; (ii) generation of up to 5 * 10(15) mol of NOx by
      the impact pressure wave and other sources; (iii) release of up to 6,500 Pg C as
      CO2 from vaporization of carbonate rocks, wildfires, and soil carbon decay; and
      (iv) ocean overturn bringing high-CO2 water to the surface. We find that the
      acidification produced by most processes is too weak to explain calcifier
      extinctions. Sulfuric acid additions could have made the surface ocean extremely
      undersaturated (Omegacalcite <0.5), but only if they reached the ocean very
      rapidly (over a few days) and if the quantity added was at the top end of
      literature estimates. We therefore conclude that severe ocean acidification might
      have been, but most likely was not, responsible for the great extinctions of
      planktonic calcifiers and ammonites at the end of the Cretaceous. 

PMID- 25964351
TI  - Pheromones mediating copulation and attraction in Drosophila.
AB  - Intraspecific olfactory signals known as pheromones play important roles in
      insect mating systems. In the model Drosophila melanogaster, a key part of the
      pheromone-detecting system has remained enigmatic through many years of research
      in terms of both its behavioral significance and its activating ligands. Here we
      show that Or47b-and Or88a-expressing olfactory sensory neurons (OSNs) detect the
      fly-produced odorants methyl laurate (ML), methyl myristate, and methyl
      palmitate. Fruitless (fru(M))-positive Or47b-expressing OSNs detect ML
      exclusively, and Or47b- and Or47b-expressing OSNs are required for optimal male
      copulation behavior. In addition, activation of Or47b-expressing OSNs in the male
      is sufficient to provide a competitive mating advantage. We further find that the
      vigorous male courtship displayed toward oenocyte-less flies is attributed to an
      oenocyte-independent sustained production of the Or47b ligand, ML. In addition,
      we reveal that Or88a-expressing OSNs respond to all three compounds, and that
      these neurons are necessary and sufficient for attraction behavior in both males
      and females. Beyond the OSN level, information regarding the three fly odorants
      is transferred from the antennal lobe to higher brain centers in two dedicated
      neural lines. Finally, we find that both Or47b- and Or88a-based systems and their
      ligands are remarkably conserved over a number of drosophilid species. Taken
      together, our results close a significant gap in the understanding of the
      olfactory background to Drosophila mating and attraction behavior; while
      reproductive isolation barriers between species are created mainly by species
      specific signals, the mating enhancing signal in several Drosophila species is
      conserved. 

PMID- 25964352
TI  - Human caspase-4 mediates noncanonical inflammasome activation against gram
      negative bacterial pathogens.
AB  - Inflammasomes are critical for host defense against bacterial pathogens. In
      murine macrophages infected by gram-negative bacteria, the canonical inflammasome
      activates caspase-1 to mediate pyroptotic cell death and release of IL-1 family
      cytokines. Additionally, a noncanonical inflammasome controlled by caspase-11
      induces cell death and IL-1 release. However, humans do not encode caspase-11.
      Instead, humans encode two putative orthologs: caspase-4 and caspase-5. Whether
      either ortholog functions similar to caspase-11 is poorly defined. Therefore, we
      sought to define the inflammatory caspases in primary human macrophages that
      regulate inflammasome responses to gram-negative bacteria. We find that human
      macrophages activate inflammasomes specifically in response to diverse gram
      negative bacterial pathogens that introduce bacterial products into the host
      cytosol using specialized secretion systems. In primary human macrophages, IL
      1beta secretion requires the caspase-1 inflammasome, whereas IL-1alpha release
      and cell death are caspase-1-independent. Instead, caspase-4 mediates IL-1alpha
      release and cell death. Our findings implicate human caspase-4 as a critical
      regulator of noncanonical inflammasome activation that initiates defense against
      bacterial pathogens in primary human macrophages. 

PMID- 25964353
TI  - The two-domain tree of life is linked to a new root for the Archaea.
AB  - One of the most fundamental questions in evolutionary biology is the origin of
      the lineage leading to eukaryotes. Recent phylogenomic analyses have indicated an
      emergence of eukaryotes from within the radiation of modern Archaea and
      specifically from a group comprising Thaumarchaeota/"Aigarchaeota" (candidate
      phylum)/Crenarchaeota/Korarchaeota (TACK). Despite their major implications,
      these studies were all based on the reconstruction of universal trees and left
      the exact placement of eukaryotes with respect to the TACK lineage unclear. Here
      we have applied an original two-step approach that involves the separate analysis
      of markers shared between Archaea and eukaryotes and between Archaea and
      Bacteria. This strategy allowed us to use a larger number of markers and greater
      taxonomic coverage, obtain high-quality alignments, and alleviate tree
      reconstruction artifacts potentially introduced when analyzing the three domains
      simultaneously. Our results robustly indicate a sister relationship of eukaryotes
      with the TACK superphylum that is strongly associated with a distinct root of the
      Archaea that lies within the Euryarchaeota, challenging the traditional topology
      of the archaeal tree. Therefore, if we are to embrace an archaeal origin for
      eukaryotes, our view of the evolution of the third domain of life will have to be
      profoundly reconsidered, as will many areas of investigation aimed at inferring
      ancestral characteristics of early life and Earth. 

PMID- 25964354
TI  - Optimized tools for multicolor stochastic labeling reveal diverse stereotyped
      cell arrangements in the fly visual system.
AB  - We describe the development and application of methods for high-throughput
      neuroanatomy in Drosophila using light microscopy. These tools enable efficient
      multicolor stochastic labeling of neurons at both low and high densities.
      Expression of multiple membrane-targeted and distinct epitope-tagged proteins is
      controlled both by a transcriptional driver and by stochastic, recombinase
      mediated excision of transcription-terminating cassettes. This MultiColor FlpOut
      (MCFO) approach can be used to reveal cell shapes and relative cell positions and
      to track the progeny of precursor cells through development. Using two different
      recombinases, the number of cells labeled and the number of color combinations
      observed in those cells can be controlled separately. We demonstrate the utility
      of MCFO in a detailed study of diversity and variability of Distal medulla (Dm)
      neurons, multicolumnar local interneurons in the adult visual system. Similar to
      many brain regions, the medulla has a repetitive columnar structure that supports
      parallel information processing together with orthogonal layers of cell processes
      that enable communication between columns. We find that, within a medulla layer,
      processes of the cells of a given Dm neuron type form distinct patterns that
      reflect both the morphology of individual cells and the relative positions of
      their arbors. These stereotyped cell arrangements differ between cell types and
      can even differ for the processes of the same cell type in different medulla
      layers. This unexpected diversity of coverage patterns provides multiple
      independent ways of integrating visual information across the retinotopic columns
      and implies the existence of multiple developmental mechanisms that generate
      these distinct patterns. 

PMID- 25964356
TI  - Regulation of AMPA receptor phosphorylation by the neuropeptide PACAP38.
AB  - Dynamic changes in synaptic strength are thought to be critical for higher brain
      function such as learning and memory. Alterations in synaptic strength can result
      from modulation of AMPA receptor (AMPAR) function and trafficking to synaptic
      sites. The phosphorylation state of AMPAR subunits is one mechanism by which
      cells regulate receptor function and trafficking. Receptor phosphorylation is in
      turn regulated by extracellular signals; these include neuronal activity,
      neuropeptides, and neuromodulators such as dopamine and norepinephrine (NE).
      Although numerous studies have reported that the neuropeptide pituitary adenylate
      cyclase activating polypeptide 38 (PACAP38) alters hippocampal CA1 synaptic
      strength and GluA1 synaptic localization, its effect on AMPAR phosphorylation
      state has not been explored. We determined that PACAP38 stimulation of
      hippocampal cultures increased phosphorylation of S845, and decreased
      phosphorylation of T840 on the GluA1 AMPAR subunit. Increases in GluA1 S845
      phosphorylation primarily occurred via PAC1 and VPAC2 receptor activation,
      whereas a reduction in GluA1 T840 phosphorylation was largely driven by PAC1
      receptor activation and to a lesser extent by VPAC1 and VPAC2 receptor
      activation. GluA1 S845 phosphorylation could be blocked by a PKA inhibitor, and
      GluA1 T840 dephosphorylation could be blocked by a protein phosphatase 1/2A
      (PP1/PP2A) inhibitor and was partly blocked by a NMDA receptor (NMDAR)
      antagonist. These results demonstrate that the neuropeptide PACAP38 inversely
      regulates the phosphorylation of two distinct sites on GluA1 and may play an
      important role modulating AMPAR function and synaptic plasticity in the brain. 

PMID- 25964357
TI  - Crop rotations in the sea: Increasing returns and reducing risk of collapse in
      sea cucumber fisheries.
AB  - Rotational harvesting is one of the oldest management strategies applied to
      terrestrial and marine natural resources, with crop rotations dating back to the
      time of the Roman Empire. The efficacy of this strategy for sessile marine
      species is of considerable interest given that these resources are vital to
      underpin food security and maintain the social and economic wellbeing of small
      scale and commercial fishers globally. We modeled the rotational zone strategy
      applied to the multispecies sea cucumber fishery in Australia's Great Barrier
      Reef Marine Park and show a substantial reduction in the risk of localized
      depletion, higher long-term yields, and improved economic performance. We
      evaluated the performance of rotation cycles of different length and show an
      improvement in biological and economic performance with increasing time between
      harvests up to 6 y. As sea cucumber fisheries throughout the world succumb to
      overexploitation driven by rising demand, there has been an increasing demand for
      robust assessments of fishery sustainability and a need to address local
      depletion concerns. Our results provide motivation for increased use of
      relatively low-information, low-cost, comanagement rotational harvest approaches
      in coastal and reef systems globally. 

PMID- 25964355
TI  - A hypothesis to reconcile the physical and chemical unfolding of proteins.
AB  - High pressure (HP) or urea is commonly used to disturb folding species. Pressure
      favors the reversible unfolding of proteins by causing changes in the volumetric
      properties of the protein-solvent system. However, no mechanistic model has fully
      elucidated the effects of urea on structure unfolding, even though protein-urea
      interactions are considered to be crucial. Here, we provide NMR spectroscopy and
      3D reconstructions from X-ray scattering to develop the "push-and-pull"
      hypothesis, which helps to explain the initial mechanism of chemical unfolding in
      light of the physical events triggered by HP. In studying MpNep2 from
      Moniliophthora perniciosa, we tracked two cooperative units using HP-NMR as
      MpNep2 moved uphill in the energy landscape; this process contrasts with the
      overall structural unfolding that occurs upon reaching a threshold concentration
      of urea. At subdenaturing concentrations of urea, we were able to trap a state in
      which urea is preferentially bound to the protein (as determined by NMR
      intensities and chemical shifts); this state is still folded and not additionally
      exposed to solvent [fluorescence and small-angle X-ray scattering (SAXS)]. This
      state has a higher susceptibility to pressure denaturation (lower p1/2 and larger
      DeltaVu); thus, urea and HP share concomitant effects of urea binding and pulling
      and water-inducing pushing, respectively. These observations explain the
      differences between the molecular mechanisms that control the physical and
      chemical unfolding of proteins, thus opening up new possibilities for the study
      of protein folding and providing an interpretation of the nature of cooperativity
      in the folding and unfolding processes. 

PMID- 25964358
TI  - A decline in prosocial language helps explain public disapproval of the US
      Congress.
AB  - Talking about helping others makes a person seem warm and leads to social
      approval. This work examines the real world consequences of this basic, social
      cognitive phenomenon by examining whether record-low levels of public approval of
      the US Congress may, in part, be a product of declining use of prosocial language
      during Congressional debates. A text analysis of all 124 million words spoken in
      the House of Representatives between 1996 and 2014 found that declining levels of
      prosocial language strongly predicted public disapproval of Congress 6 mo later.
      Warm, prosocial language still predicted public approval when removing the
      effects of societal and global factors (e.g., the September 11 attacks) and
      Congressional efficacy (e.g., passing bills), suggesting that prosocial language
      has an independent, direct effect on social approval. 

PMID- 25964359
TI  - Circuit-dependent striatal PKA and ERK signaling underlies rapid behavioral shift
      in mating reaction of male mice.
AB  - The selection of reward-seeking and aversive behaviors is controlled by two
      distinct D1 and D2 receptor-expressing striatal medium spiny neurons, namely the
      direct pathway MSNs (dMSNs) and the indirect pathway MSNs (iMSNs), but the
      dynamic modulation of signaling cascades of dMSNs and iMSNs in behaving animals
      remains largely elusive. We developed an in vivo methodology to monitor Forster
      resonance energy transfer (FRET) of the activities of PKA and ERK in either dMSNs
      or iMSNs by microendoscopy in freely moving mice. PKA and ERK were coordinately
      but oppositely regulated between dMSNs and iMSNs by rewarding cocaine
      administration and aversive electric shocks. Notably, the activities of PKA and
      ERK rapidly shifted when male mice became active or indifferent toward female
      mice during mating behavior. Importantly, manipulation of PKA cascades by the
      Designer Receptor recapitulated active and indifferent mating behaviors,
      indicating a causal linkage of a dynamic activity shift of PKA and ERK between
      dMSNs and iMSNs in action selection. 

PMID- 25964360
TI  - Holographic patterning of high-performance on-chip 3D lithium-ion microbatteries.
AB  - As sensors, wireless communication devices, personal health monitoring systems,
      and autonomous microelectromechanical systems (MEMS) become distributed and
      smaller, there is an increasing demand for miniaturized integrated power sources.
      Although thin-film batteries are well-suited for on-chip integration, their
      energy and power per unit area are limited. Three-dimensional electrode designs
      have potential to offer much greater power and energy per unit area; however,
      efforts to date to realize 3D microbatteries have led to prototypes with solid
      electrodes (and therefore low power) or mesostructured electrodes not compatible
      with manufacturing or on-chip integration. Here, we demonstrate an on-chip
      compatible method to fabricate high energy density (6.5 MUWh cm(-2)?MUm(-1)) 3D
      mesostructured Li-ion microbatteries based on LiMnO2 cathodes, and NiSn anodes
      that possess supercapacitor-like power (3,600 MUW cm(-2)?MUm(-1) peak). The
      mesostructured electrodes are fabricated by combining 3D holographic lithography
      with conventional photolithography, enabling deterministic control of both the
      internal electrode mesostructure and the spatial distribution of the electrodes
      on the substrate. The resultant full cells exhibit impressive performances, for
      example a conventional light-emitting diode (LED) is driven with a 500-MUA peak
      current (600-C discharge) from a 10-MUm-thick microbattery with an area of 4
      mm(2) for 200 cycles with only 12% capacity fade. A combined experimental and
      modeling study where the structural parameters of the battery are modulated
      illustrates the unique design flexibility enabled by 3D holographic lithography
      and provides guidance for optimization for a given application. 

PMID- 25964361
TI  - Resilience and reactivity of global food security.
AB  - The escalating food demand by a growing and increasingly affluent global
      population is placing unprecedented pressure on the limited land and water
      resources of the planet, underpinning concerns over global food security and its
      sensitivity to shocks arising from environmental fluctuations, trade policies,
      and market volatility. Here, we use country-specific demographic records along
      with food production and trade data for the past 25 y to evaluate the stability
      and reactivity of the relationship between population dynamics and food
      availability. We develop a framework for the assessment of the resilience and the
      reactivity of the coupled population-food system and suggest that over the past
      two decades both its sensitivity to external perturbations and susceptibility to
      instability have increased. 

PMID- 25964362
TI  - Random coil negative control reproduces the discrepancy between scattering and
      FRET measurements of denatured protein dimensions.
AB  - Small-angle scattering studies generally indicate that the dimensions of unfolded
      single-domain proteins are independent (to within experimental uncertainty of a
      few percent) of denaturant concentration. In contrast, single-molecule FRET
      (smFRET) studies invariably suggest that protein unfolded states contract
      significantly as the denaturant concentration falls from high (~6 M) to low (~1
      M). Here, we explore this discrepancy by using PEG to perform a hitherto absent
      negative control. This uncharged, highly hydrophilic polymer has been shown by
      multiple independent techniques to behave as a random coil in water, suggesting
      that it is unlikely to expand further on the addition of denaturant. Consistent
      with this observation, small-angle neutron scattering indicates that the
      dimensions of PEG are not significantly altered by the presence of either
      guanidine hydrochloride or urea. smFRET measurements on a PEG construct modified
      with the most commonly used FRET dye pair, however, produce denaturant-dependent
      changes in transfer efficiency similar to those seen for a number of unfolded
      proteins. Given the vastly different chemistries of PEG and unfolded proteins and
      the significant evidence that dye-free PEG is well-described as a denaturant
      independent random coil, this similarity raises questions regarding the
      interpretation of smFRET data in terms of the hydrogen bond- or hydrophobically
      driven contraction of the unfolded state at low denaturant. 

PMID- 25964363
TI  - Early land use and centennial scale changes in lake-water organic carbon prior to
      contemporary monitoring.
AB  - Organic carbon concentrations have increased in surface waters across parts of
      Europe and North America during the past decades, but the main drivers causing
      this phenomenon are still debated. A lack of observations beyond the last few
      decades inhibits a better mechanistic understanding of this process and thus a
      reliable prediction of future changes. Here we present past lake-water organic
      carbon trends inferred from sediment records across central Sweden that allow us
      to assess the observed increase on a centennial to millennial time scale. Our
      data show the recent increase in lake-water carbon but also that this increase
      was preceded by a landscape-wide, long-term decrease beginning already A.D. 1450
      1600. Geochemical and biological proxies reveal that these dynamics coincided
      with an intensification of human catchment disturbance that decreased over the
      past century. Catchment disturbance was driven by the expansion and later
      cessation of widespread summer forest grazing and farming across central
      Scandinavia. Our findings demonstrate that early land use strongly affected past
      organic carbon dynamics and suggest that the influence of historical landscape
      utilization on contemporary changes in lake-water carbon levels has thus far been
      underestimated. We propose that past changes in land use are also a strong
      contributing factor in ongoing organic carbon trends in other regions that
      underwent similar comprehensive changes due to early cultivation and grazing over
      centuries to millennia. 

PMID- 25964364
TI  - Rate, spectrum, and evolutionary dynamics of spontaneous epimutations.
AB  - Stochastic changes in cytosine methylation are a source of heritable epigenetic
      and phenotypic diversity in plants. Using the model plant Arabidopsis thaliana,
      we derive robust estimates of the rate at which methylation is spontaneously
      gained (forward epimutation) or lost (backward epimutation) at individual
      cytosines and construct a comprehensive picture of the epimutation landscape in
      this species. We demonstrate that the dynamic interplay between forward and
      backward epimutations is modulated by genomic context and show that subtle
      contextual differences have profoundly shaped patterns of methylation diversity
      in A. thaliana natural populations over evolutionary timescales. Theoretical
      arguments indicate that the epimutation rates reported here are high enough to
      rapidly uncouple genetic from epigenetic variation, but low enough for new
      epialleles to sustain long-term selection responses. Our results provide new
      insights into methylome evolution and its population-level consequences. 

PMID- 25964365
TI  - Superficial white matter fiber systems impede detection of long-range cortical
      connections in diffusion MR tractography.
AB  - In vivo tractography based on diffusion magnetic resonance imaging (dMRI) has
      opened new doors to study structure-function relationships in the human brain.
      Initially developed to map the trajectory of major white matter tracts, dMRI is
      used increasingly to infer long-range anatomical connections of the cortex.
      Because axonal projections originate and terminate in the gray matter but travel
      mainly through the deep white matter, the success of tractography hinges on the
      capacity to follow fibers across this transition. Here we demonstrate that the
      complex arrangement of white matter fibers residing just under the cortical sheet
      poses severe challenges for long-range tractography over roughly half of the
      brain. We investigate this issue by comparing dMRI from very-high-resolution ex
      vivo macaque brain specimens with histological analysis of the same tissue. Using
      probabilistic tracking from pure gray and white matter seeds, we found that ~50%
      of the cortical surface was effectively inaccessible for long-range diffusion
      tracking because of dense white matter zones just beneath the infragranular
      layers of the cortex. Analysis of the corresponding myelin-stained sections
      revealed that these zones colocalized with dense and uniform sheets of axons
      running mostly parallel to the cortical surface, most often in sulcal regions but
      also in many gyral crowns. Tracer injection into the sulcal cortex demonstrated
      that at least some axonal fibers pass directly through these fiber systems.
      Current and future high-resolution dMRI studies of the human brain will need to
      develop methods to overcome the challenges posed by superficial white matter
      systems to determine long-range anatomical connections accurately. 

PMID- 25964366
TI  - Hydrological change in Southern Europe responding to increasing North Atlantic
      overturning during Greenland Stadial 1.
AB  - Greenland Stadial 1 (GS-1) was the last of a long series of severe cooling
      episodes in the Northern Hemisphere during the last glacial period. Numerous
      North Atlantic and European records reveal the intense environmental impact of
      that stadial, whose origin is attributed to an intense weakening of the Atlantic
      Meridional Overturning Circulation in response to freshening of the North
      Atlantic. Recent high-resolution studies of European lakes revealed a mid-GS-1
      transition in the climatic regimes. The geographical extension of such
      atmospheric changes and their potential coupling with ocean dynamics still
      remains unclear. Here we use a subdecadally resolved stalagmite record from the
      Northern Iberian Peninsula to further investigate the timing and forcing of this
      transition. A solid interpretation of the environmental changes detected in this
      new, accurately dated, stalagmite record is based on a parallel cave monitoring
      exercise. This record reveals a gradual transition from dry to wet conditions
      starting at 12,500 y before 2000 A.D. in parallel to a progressive warming of the
      subtropical Atlantic Ocean. The observed atmospheric changes are proposed to be
      led by a progressive resumption of the North Atlantic convection and highlight
      the complex regional signature of GS-1, very distinctive from previous stadial
      events. 

PMID- 25964367
TI  - Atmospheric composition 1 million years ago from blue ice in the Allan Hills,
      Antarctica.
AB  - Here, we present direct measurements of atmospheric composition and Antarctic
      climate from the mid-Pleistocene (~1 Ma) from ice cores drilled in the Allan
      Hills blue ice area, Antarctica. The 1-Ma ice is dated from the deficit in (40)Ar
      relative to the modern atmosphere and is present as a stratigraphically disturbed
      12-m section at the base of a 126-m ice core. The 1-Ma ice appears to represent
      most of the amplitude of contemporaneous climate cycles and CO2 and CH4
      concentrations in the ice range from 221 to 277 ppm and 411 to 569 parts per
      billion (ppb), respectively. These concentrations, together with measured deltaD
      of the ice, are at the warm end of the field for glacial-interglacial cycles of
      the last 800 ky and span only about one-half of the range. The highest CO2 values
      in the 1-Ma ice fall within the range of interglacial values of the last 400 ka
      but are up to 7 ppm higher than any interglacial values between 450 and 800 ka.
      The lowest CO2 values are 30 ppm higher than during any glacial period between
      450 and 800 ka. This study shows that the coupling of Antarctic temperature and
      atmospheric CO2 extended into the mid-Pleistocene and demonstrates the
      feasibility of discontinuously extending the current ice core record beyond 800
      ka by shallow coring in Antarctic blue ice areas. 

PMID- 25964368
TI  - Progressive supra-nuclear palsy: frequency of cardinal extrapyramidal features at
      first presentation.
AB  - OBJECTIVES: Cardinal extrapyramidal features of progressive supranuclear palsy
      (PSP) help in clinically differentiating this condition from Parkinson's disease
      and other Parkinsonian syndromes. However, not all extrapyramidal features may be
      initially present, thus posing a difficulty in early diagnosis. We studied their
      frequency at the time of first presentation. METHODS: Patients diagnosed
      clinically with PSP using the National Institute for Neurological Disorders and
      Society for PSP (NINDS/SPSP) criteria and seen between August 2010 and April 2013
      were examined for the presence, 'presence with deviation' or absence of six
      extrapyramidal features: axial rigidity, symmetry, extended posture, backward
      falls, absence of tremors and lack of levodopa response. RESULTS: Twenty-eight
      patients (mean (SD) age 64.86 (9.72) years; 16 (57%) men) met the inclusion
      criteria. Of these, 14% had all six extrapyramidal features associated with PSP,
      39% had five, 29% had four, 14% had three and 4% had two. The most frequent
      extrapyramidal sign was axial rigidity (68%). Axial plus peripheral rigidity was
      found in 18% of patients and peripheral rigidity alone in 14%. Extrapyramidal
      features were symmetrical in 29% and asymmetrical beyond 1 year in 29%. Body
      posture was extended in 46% and flexed in 21%. Backward falls were found in 50%
      and forward falls in 11%. Pill-rolling tremors were observed in 29%. Response to
      levodopa therapy was poor in 21% and good beyond 6 months in 39%. CONCLUSIONS:
      Only 14% of PSP patients present with all six cardinal extrapyramidal features.
      Also, deviations from standard descriptions are common in the initial stages of
      disease.

PMID- 25964369
TI  - Process evaluation of a multi-component intervention to reduce infectious
      diseases and improve hygiene and well-being among school children: the Hi Five
      study.
AB  - The Hi Five study was a three-armed cluster randomized controlled trial designed
      to reduce infections and improve hygiene and well-being among pupils.
      Participating schools (n = 43) were randomized into either control (n = 15) or
      one of two intervention groups (n = 28). The intervention consisted of three
      components: (i) a curriculum (ii) mandatory daily hand washing before lunch (iii)
      extra cleaning of school toilets. The aim of this study was to evaluate the
      implementation and to identify challenges to program implementation. Several data
      sources were used, including observations of school toilets, semi-structured
      interviews with school coordinators (n = 4), focus groups with pupils (n = 6) and
      teachers (n = 5), and questionnaires among pupils (n = 5440), teachers (n = 387)
      and school coordinators (n = 28). This study indicates that the curriculum was
      successfully implemented at most schools, and that teachers and pupils reacted
      positively to this part of the intervention. However, daily hand washing before
      lunch seems to be difficult to implement. Overall, the implementation process was
      affected by several factors such as poor sanitary facilities, lack of time and
      prioritization and objections against the increasing tendency to place the
      responsibility for child-rearing tasks on schools. This study reveals the strong
      and weak parts of the Hi Five study and can guide program improvement. 

PMID- 25964370
TI  - Bcl11b is essential for group 2 innate lymphoid cell development.
AB  - Group 2 innate lymphoid cells (ILC2s) are often found associated with mucosal
      surfaces where they contribute to protective immunity, inappropriate allergic
      responses, and tissue repair. Although we know they develop from a common
      lymphoid progenitor in the bone marrow (BM), the specific lineage path and
      transcriptional regulators that are involved are only starting to emerge. After
      ILC2 gene expression analysis we investigated the role of Bcl11b, a factor
      previously linked to T cell commitment, in ILC2 development. Using combined
      Bcl11b-tom and Id2-gfp reporter mice, we show that Bcl11b is expressed in ILC2
      precursors in the BM and maintained in mature ILC2s. In vivo deletion of Bcl11b,
      by conditional tamoxifen-induced depletion or by Bcl11b(-/-) fetal liver chimera
      reconstitution, demonstrates that ILC2s are wholly dependent on Bcl11b for their
      development. Notably, in the absence of Bcl11b there is a concomitant expansion
      of the RORgammat(+) ILC3 population, suggesting that Bcl11b may negatively
      regulate this lineage. Using Nippostrongylus brasiliensis infection, we reveal
      that the absence of Bcl11b leads to impaired worm expulsion, caused by a deficit
      in ILC2s, whereas Citrobacter rodentium infection is cleared efficiently. These
      data clearly establish Bcl11b as a new factor in the differentiation of ILC2s. 

PMID- 25964371
TI  - The transcription factor Bcl11b is specifically expressed in group 2 innate
      lymphoid cells and is essential for their development.
AB  - Group 2 innate lymphoid cells (ILCs), or ILC2s, are a subset of recently
      identified ILCs, which play important roles in innate immunity by producing type
      2 effector cytokines. Several transcription factors have been found to have
      critical functions in the development of both ILC2s and T cells. We report here
      that Bcl11b, a transcription factor essential in T cell lineage commitment and
      maintenance, is specifically expressed in progenitors committed to the ILC2
      lineage and is required for ILC2 development. The Bcl11b gene is expressed in
      ~28% of ILC progenitors (ILCPs; common helper innate lymphoid progenitors or
      ILCPs expressing either ID2 or promyelocytic leukemia zinc finger, respectively).
      Both in vitro and in vivo, these Bcl11b-expressing early ILCPs generate only
      ILC2s. Inactivation of Bcl11b causes a complete loss of ILC2 development from
      hematopoietic progenitors, which is confirmed upon immune challenge with either
      papain administration or influenza virus infection.

PMID- 25964373
TI  - Ruptured distal AICA pseudoaneurysm presenting years after vestibular schwannoma
      resection and radiation.
AB  - Distal anterior inferior cerebellar artery (AICA) pseudoaneurysms are very rare
      lesions. Although cases have been previously reported, only a few have been
      reported as a result of vestibular schwannoma (VS) radiation, none have been
      reported as a result of VS resection, and only one has been reported as treated
      with parent vessel occlusion (PVO) with n-butyl cyanoacrylate (nBCA). We report a
      case of a 65-year-old man with a history of right-sided VS surgery and radiation
      who presented years later with a ruptured pseudoaneurysm of the distal right AICA
      and was treated with endovascular PVO using nBCA. The aneurysm was completely
      obliterated and the patient had no worsening of symptoms or neurological exam.
      The case illustrates a very rare complication of VS surgery and radiation as well
      as an effective treatment for distal AICA aneurysms. 

PMID- 25964374
TI  - Response: successful endovascular treatment of three fusiform cerebral aneurysms
      with the pipeline embolization device in a patient with dilating HIV
      vasculopathy. Authors' reply.

PMID- 25964372
TI  - An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in
      a tissue repair mode.
AB  - Pentraxin 3 (PTX3) is a fluid-phase pattern recognition molecule and a key
      component of the humoral arm of innate immunity. In four different models of
      tissue damage in mice, PTX3 deficiency was associated with increased fibrin
      deposition and persistence, and thicker clots, followed by increased collagen
      deposition, when compared with controls. Ptx3-deficient macrophages showed
      defective pericellular fibrinolysis in vitro. PTX3-bound fibrinogen/fibrin and
      plasminogen at acidic pH and increased plasmin-mediated fibrinolysis. The second
      exon-encoded N-terminal domain of PTX3 recapitulated the activity of the intact
      molecule. Thus, a prototypic component of humoral innate immunity, PTX3, plays a
      nonredundant role in the orchestration of tissue repair and remodeling. Tissue
      acidification resulting from metabolic adaptation during tissue repair sets PTX3
      in a tissue remodeling and repair mode, suggesting that matrix and microbial
      recognition are common, ancestral features of the humoral arm of innate immunity.

PMID- 25964375
TI  - Early arrival at the emergency department is associated with better collaterals,
      smaller established infarcts and better clinical outcomes with endovascular
      stroke therapy: SWIFT study.
AB  - BACKGROUND AND PURPOSE: Increasing time from symptom onset to emergency
      department arrival may incur greater ischemic injury and decreased likelihood of
      good outcomes after acute stroke therapy. The impact of time may be assessed
      bythe extent of acute CT changes, status of collateral vessels, and clinical
      outcomes. METHODS: The SOLITAIRE FR With the Intention For Thrombectomy (SWIFT)
      trial comparing two neurothrombectomy treatments was analyzed by time, Alberta
      Stroke Program Early CT Scores (ASPECTS), angiographic collaterals, and 90-day
      modified Rankin Scale outcomes. We determined the interaction of time with
      ASPECTS, collateral grade, reperfusion, and clinical outcomes, with established
      determinants of angiographic and clinical outcomes as covariates. RESULTS: 137
      patients (52% female) of mean age 67+/-12 years and median pretreatment NIH
      Stroke Scale score 18 (range 8-28) were enrolled. Median onset to door (OTD) time
      was 180 min (IQR 95-250). Presentation within 3 h of last known well was
      associated with absence of any prestroke disability and presence of atrial
      fibrillation but was unrelated to age, sex, other vascular risk factors, deficit
      severity, glucose level, or blood pressure. Worse collaterals were noted with
      longer OTD intervals: collateral grade 0-1 (n=32): mean 232+/-84 min; grade 2
      (n=48): 164+/-99 min; grade 3 (n=35): 155+/-104 min; grade 4 (n=4): 54+/-16 min
      (p<0.001). Later presentation was associated with more extensive early infarct
      imaging changes (median ASPECTS 8 (IQR 7-9) >3 h vs 9 (IQR 8-10) <3 h, p=0.015).
      Multivariable analyses identified time >3 h as the only predictor of extensive
      infarct on imaging (ASPECTS <=7), p=0.003. Earlier presentation was strongly
      associated with better 90-day modified Rankin Scale outcomes (p<0.001).
      CONCLUSIONS: Time was a critical factor in successful clinical outcomes for
      neurothrombectomy in the SWIFT trial. Shorter times to presentation were
      associated with better collaterals, smaller established infarcts, and better
      clinical outcome after revascularization.

PMID- 25964376
TI  - Outcomes of vertebroplasty compared with kyphoplasty: a systematic review and
      meta-analysis.
AB  - BACKGROUND AND PURPOSE: Many studies demonstrate that both kyphoplasty and
      vertebroplasty are superior to conservative therapy in the treatment of
      osteoporotic vertebral body compression fractures. We performed a systematic
      review and meta-analysis of studies comparing the outcomes of vertebroplasty and
      kyphoplasty, which included prospective non-randomized, retrospective
      comparative, and randomized studies. MATERIALS AND METHODS: We searched MEDLINE,
      EMBASE, and the Web of Science databases for studies of kyphoplasty versus
      vertebroplasty from 1 January 1990 to 30 November 2014 and compared the following
      outcomes: procedure characteristics, pain and disability improvement,
      complications and anatomic outcomes. A subgroup analysis was performed comparing
      pain outcomes based on the risk of bias. RESULTS: 29 studies enrolling 2838
      patients (1384 kyphoplasty and 1454 vertebroplasty) were included. 16 prospective
      non-randomized studies, 10 retrospective comparative studies, and 3 randomized
      controlled studies were included. No significant differences were found in mean
      pain scores between the two groups postoperatively (2.9+/-1.5 kyphoplasty vs
      2.9+/-1.7 vertebroplasty, p=0.39) and at 12 months (2.7+/-1.8 kyphoplasty vs
      3.2+/-1.8 vertebroplasty, p=0.64). No significant differences were found in
      disability postoperatively (34.7+/-7.1 kyphoplasty group vs 36.3+/-7.8
      vertebroplasty group, p=0.74) or at 12 months (28.3+/-16 kyphoplasty group vs
      29.6+/-13.9 vertebroplasty group, p=0.70). Kyphoplasty was associated with lower
      odds of new fractures (p=0.06), less extraosseous cement leakage (p<0.01), and
      greater reduction in kyphotic angle (p<0.01). CONCLUSIONS: No significant
      difference was found between vertebroplasty and kyphoplasty in short- and long
      term pain and disability outcomes. Further studies are needed to better determine
      if any particular subgroups of patients would benefit more from vertebroplasty or
      kyphoplasty in the treatment of vertebral body compression fractures.

PMID- 25964377
TI  - Lower vertebral-epidural spinal arteriovenous fistulas: a unique subtype of
      vertebrovertebral arteriovenous fistula, treatable with coil and Penumbra
      Occlusion Device embolization.
AB  - A vertebral-epidural spinal arteriovenous fistula (AVF) is an abnormal
      arteriovenous shunt connecting the vertebral artery to the spinal epidural venous
      plexus, and may occur spontaneously or secondary to a variety of causes. These
      unique lesions are uncommon in adults and rarer still in children. Previous
      reports have grouped together a heterogeneous collection of such arteriovenous
      lesions, including arterial contributions from the upper and lower vertebral
      artery, with venous drainage into a variety of spinal and paraspinal collectors.
      Here, through two cases, we delineate a distinct entity, the lower vertebral-to
      epidural AVF. The salient clinical and anatomic features are summarized and
      contextualized within the broader constellation of vertebrovertebral AVF, the
      utility of a transarterial intravenous/retrograde intra-arterial endovascular
      approach is highlighted, and a new use of the Penumbra Occlusion Device (Penumbra
      Inc) for this purpose is reported. 

PMID- 25964378
TI  - Effect of Androctonus bicolor scorpion venom on serum electrolytes in rats: A 24
      h time-course study.
AB  - Black fat-tailed scorpion (Androctonus bicolor) belongs to the family Buthidae
      and is one of the most venomous scorpions in the world. The effects of A. bicolor
      venom on serum electrolytes were not known and therefore investigated in this
      study. Adult male Wistar rats were randomly divided into seven groups with five
      animals in each group. One of the groups served as control and received vehicle
      only. The animals in the remaining groups received a single subcutaneous
      injection of crude A. bicolor venom (200 MUg/kg bodyweight) and were killed at
      different time intervals including 30 min, 1 h, 2 h, 4 h, 8 h, and 24 h after
      venom injection. The results showed that scorpion venom caused significant
      increase in serum sodium levels within 30 min after injection which slightly
      subsided after 1 h and then persisted over 24 h. Serum potassium levels continued
      to significantly increase until 4 h and then slightly subsided. There were
      significant decreases in serum magnesium (Mg(+)) levels following scorpion venom
      injection, at all the time points during the course of study. Serum calcium
      levels were significantly increased during the entire course of study, whereas
      serum chloride was significantly decreased. In conclusion, A. bicolor
      envenomation in rats caused severe and persistent hypomagnesemia with accompanied
      hypernatremia, hyperkalemia, and hypercalcemia. It is important to measure serum
      Mg(+) levels in victims of scorpion envenomation, and patients with severe Mg(+)
      deficiency should be treated accordingly. 

PMID- 25964379
TI  - Fish/flaxseed oil protect against nitric oxide-induced hepatotoxicity and cell
      death in the rat liver.
AB  - Sodium nitroprusside (SNP) is an antihypertensive drug with proven toxic effects
      attributed mainly to the production of nitric oxide (NO). Polyunsaturated fatty
      acids (PUFAs) are widely regarded as functional foods and have been shown to
      ameliorate the harmful effects of many toxicants. This study examined whether
      feeding of fish oil (FO)/flaxseed oil (FXO) would have any protective effect
      against SNP-induced hepatotoxicity and cell death. Male Wistar rats were fed
      either on normal diet or with 15% FO/FXO for 15 days, following which SNP (1.5
      mg/kg body weight) was administered intraperitoneally for 7 days. Animals were
      killed after treatment, and livers were collected for further analysis. We
      observed that SNP significantly elevated tissue nitrite levels and lipid
      peroxidation (LPO) with concomitant perturbation in antioxidant defense systems
      accompanied with dysregulated glucose metabolism and pronounced cellular death.
      FO/FXO supplementation to SNP-treated rats caused reversal of tissue injury/cell
      death and markedly decreased LPO and improved antioxidant defense systems. FO/FXO
      appear to protect against SNP-induced hepatotoxicity by improving energy
      metabolism and antioxidant defense mechanism. 

PMID- 25964380
TI  - Protective effect of 17beta-estradiol on serum deprivation-induced apoptosis and
      oxidative stress in bone marrow-derived mesenchymal stem cells.
AB  - Stem cell transplantation has indicated great promise for cell therapy in a wide
      range of diseases, but poor and insufficient viability of cells within damaged
      tissues has limited its potential therapeutic effects. 17 beta-Estradiol (E2) is
      a steroid hormone that plays an important role in expression of many genes and
      regulating proliferation, viability, and intracellular redox status in different
      cell types. In this study, we aimed to assess the effect of E2 on bone marrow
      derived mesenchymal stem cells (BM-MSCs). Apoptosis was induced by serum
      deprivation (SD), and cells were exposed to E2 in the presence or absence of
      serum for varying periods of time, after which cell viability was measured by 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Expression of
      proapoptotic and antiapoptotic proteins after exposure to E2 was examined by
      Western blotting. The ability of E2 to prevent reactive oxygen species (ROS)
      production was also measured. The results indicated that E2 significantly
      enhanced the viability of the cells and protected BM-MSCs against SD-induced
      overproduction of ROS. It could reduce lipid peroxidation, total antioxidant
      power, and also Bax/Bcl-2 ratio as well as expression of caspase-3. Taken
      together, our data support that E2 treatment protects BM-MSCs against SD-induced
      damage by regulating ROS production and upregulation of
      antiapoptotic/proapoptotic proteins ratio. 

PMID- 25964381
TI  - Comparison of bioactivities, binding properties and intrafollicular levels of
      bovine follistatins.
AB  - Five isoforms of follistatin (FST) (Mr 31, 33, 35, 37, and 41  kDa) were purified
      from bovine follicular fluid (bFF). Comparison of their activin and heparan
      sulphate proteoglycan (HSP) binding properties and biopotencies in the
      neutralisation of activin A action in vitro revealed that all five isoforms bound
      activin A, but they did so with different affinities. Only the 31  kDa isoform
      (FST-288) bound to HSP. FST-288 also showed the greatest biopotency, and the 35
      and 41  kDa isoforms were the least potent. To determine whether bovine follicle
      development is associated with changing intrafollicular FST and activin profiles,
      we analysed bFF from dominant follicles (DFs) and subordinate follicles (SF)
      collected at strategic times during a synchronised oestrous cycle. Total FST,
      activin A and activin AB were measured by immunoassay, whereas individual FST
      isoforms were quantified by immunoblotting. Follicle diameter was positively
      correlated with oestrogen:progesterone ratio (r=0.56) in bFF but negatively
      correlated with activin A (r=-0.34), activin AB (r=-0.80) and 'total' FST (r=
      0.70) levels. Follicle diameter was positively correlated with the abundance of
      the 41  kDa isoform (r=0.59) but negatively correlated with the abundance of the
      33 and 31  kDa isoforms (r=-0.56 and r=-0.41 respectively). Both follicle
      statuses (DF and SF) and cycle stage affected total FST, activin A and activin B
      levels, whereas follicle status, but not cycle stage, affected the abundance of
      the 41, 37, 33 and 31  kDa FST isoforms. Collectively, these findings indicate
      that intrafollicular FST isoforms, which differ in their ability to bind and
      neutralise activins and to associate with cell-surface proteoglycans, show
      divergent changes during follicle development. Enhanced FST production may play
      an important negative role, either directly or via the inhibition of the positive
      effects of activins, on follicle growth and function during follicular waves.

PMID- 25964383
TI  - Altered activities of kininase II, an angiotensin converting enzyme,
      prekallikrein, and nitric oxide in Kuwaiti patients with type 2 diabetes.
AB  - The current investigation was conducted to examine kininase II or angiotensin
      converting enzyme (ACE), plasma prekallikrein (PK), and nitric oxide (NO)
      concentrations in healthy Kuwaiti subjects and newly diagnosed Kuwaiti type 2
      diabetic patients before and after treatment for 6 weeks with metformin
      hydrochloride 500 mg twice daily after meal. With the consent of volunteers,
      blood and urine samples were collected after an overnight fasting. Samples were
      collected from the diabetic patients before and after treatment for 6 weeks.
      Enzyme linked immunosorbent assay (ELISA) was carried out on the aliquoted
      samples to measure the concentration of kininase II. NO was detected via
      colorimetry. Plasma Kininase II or ACE levels were significantly (P <0.01)
      increased by 18% in untreated diabetics when compared with healthy volunteers.
      However, after treatment there was a significant decrease of 20% in their ACE
      levels. Plasma prekallikrein levels were raised significantly (P <0.01) by 28% in
      diabetic patients in contrast with the control subjects and the levels were
      significantly reduced (P <0.0001) by 44% after treatment with metformin
      hydrochloride. NO levels were found to be significantly decreased in plasma by
      56% and in urine by 62% in untreated diabetic patients as compared with the
      healthy subjects. However, when the treated diabetic patients were compared with
      untreated diabetics, there was an increase of 50% in plasma and 37% in urine
      samples. The high levels of kininase II, prekallikrein, and reduced NO may be
      partly responsible for the induction of renal, cardiac, and hypertensive
      complications associated with type 2 diabetes. Reduced NO level is an indication
      of endothelial dysfunction resulting in increased blood pressure. Oral anti
      diabetic treatment is associated with protective effects through the reduction of
      kininase II (ACE), prekallikrein, and elevation of NO levels. 

PMID- 25964385
TI  - Active play key to curbing child obesity.

PMID- 25964382
TI  - Regulation and roles of Ca2+ stores in human sperm.
AB  - [Ca(2)(+)]i signalling is a key regulatory mechanism in sperm function. In
      mammalian sperm the Ca(2)(+)-permeable plasma membrane ion channel CatSper is
      central to [Ca(2)(+)]i signalling, but there is good evidence that Ca(2)(+)
      stored in intracellular organelles is also functionally important. Here we
      briefly review the current understanding of the diversity of Ca(2)(+) stores and
      the mechanisms for the regulation of their activity. We then consider the
      evidence for the involvement of these stores in [Ca(2)(+)]i signalling in
      mammalian (primarily human) sperm, the agonists that may activate these stores
      and their role in control of sperm function. Finally we consider the evidence
      that membrane Ca(2)(+) channels and stored Ca(2)(+) may play discrete roles in
      the regulation of sperm activities and propose a mechanism by which these
      different components of the sperm Ca(2)(+)-signalling apparatus may interact to
      generate complex and spatially diverse [Ca(2)(+)]i signals.

PMID- 25964384
TI  - Conserved RNA secondary structures and long-range interactions in hepatitis C
      viruses.
AB  - Hepatitis C virus (HCV) is a hepatotropic virus with a plus-strand RNA genome of
      ~9.600 nt. Due to error-prone replication by its RNA-dependent RNA polymerase
      (RdRp) residing in nonstructural protein 5B (NS5B), HCV isolates are grouped into
      seven genotypes with several subtypes. By using whole-genome sequences of 106 HCV
      isolates and secondary structure alignments of the plus-strand genome and its
      minus-strand replication intermediate, we established refined secondary
      structures of the 5' untranslated region (UTR), the cis-acting replication
      element (CRE) in NS5B, and the 3' UTR. We propose an alternative structure in the
      5' UTR, conserved secondary structures of 5B stem-loop (SL)1 and 5BSL2, and four
      possible structures of the X-tail at the very 3' end of the HCV genome. We
      predict several previously unknown long-range interactions, most importantly a
      possible circularization interaction between distinct elements in the 5' and 3'
      UTR, reminiscent of the cyclization elements of the related flaviviruses. Based
      on analogy to these viruses, we propose that the 5'-3' UTR base-pairing in the
      HCV genome might play an important role in viral RNA replication. These results
      may have important implications for our understanding of the nature of the cis
      acting RNA elements in the HCV genome and their possible role in regulating the
      mutually exclusive processes of viral RNA translation and replication. 

PMID- 25964387
TI  - Incidence of psychotic disorders among first-generation immigrants and refugees
      in Ontario.
AB  - BACKGROUND: Evidence suggests that migrant groups have an increased risk of
      psychotic disorders and that the level of risk varies by country of origin and
      host country. Canadian evidence is lacking on the incidence of psychotic
      disorders among migrants. We sought to examine the incidence of schizophrenia and
      schizoaffective disorders in first-generation immigrants and refugees in the
      province of Ontario, relative to the general population. METHODS: We constructed
      a retrospective cohort that included people aged 14-40 years residing in Ontario
      as of Apr. 1, 1999. Population-based administrative data from physician billings
      and hospital admissions were linked to data from Citizenship and Immigration
      Canada. We used Poisson regression models to calculate age- and sex-adjusted
      incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for immigrant and
      refugee groups over a 10-year period. RESULTS: In our cohort (n = 4,284,694), we
      found higher rates of psychotic disorders among immigrants from the Caribbean and
      Bermuda (IRR 1.60, 95% CI 1.29-1.98). Lower rates were found among immigrants
      from northern Europe (IRR 0.50, 95% CI 0.28-0.91), southern Europe (IRR 0.60, 95%
      CI 0.41-0.90) and East Asia (IRR 0.56, 95% CI 0.41-0.78). Refugee status was an
      independent predictor of risk among all migrants (IRR 1.27, 95% CI 1.04-1.56),
      and higher rates were found specifically for refugees from East Africa (IRR 1.95,
      95% CI 1.44-2.65) and South Asia (IRR 1.51, 95% CI 1.08-2.12). INTERPRETATION:
      The differential pattern of risk across ethnic subgroups in Ontario suggests that
      psychosocial and cultural factors associated with migration may contribute to the
      risk of psychotic disorders. Some groups may be more at risk, whereas others are
      protected.

PMID- 25964388
TI  - Regulating electronic cigarettes: finding the balance between precaution and harm
      reduction.

PMID- 25964389
TI  - Migration and risk of psychosis in the Canadian context.

PMID- 25964390
TI  - Scientists decry Canada's outdated Wi-Fi safety rules.

PMID- 25964391
TI  - Workplace insurance woes.

PMID- 25964392
TI  - Food guide under fire at obesity summit.

PMID- 25964393
TI  - Quebec reforms: necessary or overkill?

PMID- 25964394
TI  - Craniocervical deformity and myelopathy after chronic odontoid fracture.

PMID- 25964396
TI  - To be or not to be comprehensive.

PMID- 25964395
TI  - A Human Thrifty Phenotype Associated With Less Weight Loss During Caloric
      Restriction.
AB  - Successful weight loss is variable for reasons not fully elucidated. Whether
      effective weight loss results from smaller reductions in energy expenditure
      during caloric restriction is not known. We analyzed whether obese individuals
      with a "thrifty" phenotype, that is, greater reductions in 24-h energy
      expenditure during fasting and smaller increases with overfeeding, lose less
      weight during caloric restriction than those with a "spendthrift" phenotype.
      During a weight-maintaining period, 24-h energy expenditure responses to fasting
      and 200% overfeeding were measured in a whole-room indirect calorimeter.
      Volunteers then underwent 6 weeks of 50% caloric restriction. We calculated the
      daily energy deficit (kilocalories per day) during caloric restriction,
      incorporating energy intake and waste, energy expenditure, and daily activity. We
      found that a smaller reduction in 24-h energy expenditure during fasting and a
      larger response to overfeeding predicted more weight loss over 6 weeks, even
      after accounting for age, sex, race, and baseline weight, as well as a greater
      rate of energy deficit accumulation. The success of dietary weight loss efforts
      is influenced by the energy expenditure response to caloric restriction. Greater
      decreases in energy expenditure during caloric restriction predict less weight
      loss, indicating the presence of thrifty and spendthrift phenotypes in obese
      humans. 

PMID- 25964398
TI  - Impact of UK Primary Care Policy Reforms on Short-Stay Unplanned Hospital
      Admissions for Children With Primary Care-Sensitive Conditions.
AB  - PURPOSE: We aimed to assess the impact of UK primary care policy reforms
      implemented in April 2004 on potentially avoidable unplanned short-stay hospital
      admissions for children with primary care-sensitive conditions. METHODS: We
      conducted an interrupted time series analysis of hospital admissions for all
      children aged younger than 15 years in England between April 2000 and March 2012
      using data from National Health Service public hospitals in England. The main
      outcomes were annual short-stay (<2-day) unplanned hospital admission rates for
      primary care-sensitive infectious and chronic conditions. RESULTS: There were 7.8
      million unplanned admissions over the study period. More than one-half (4,144,729
      of 7,831,633) were short-stay admissions for potentially avoidable infectious and
      chronic conditions. The primary care policy reforms of April 2004 were associated
      with an 8% increase in short-stay admission rates for chronic conditions,
      equivalent to 8,500 additional admissions, above the 3% annual increasing trend.
      Policy reforms were not associated with an increase in short-stay admission rates
      for infectious illness, which were increasing by 5% annually before April 2004.
      The proportion of primary care-referred admissions was falling before the
      reforms, and there were further sharp reductions in 2004. CONCLUSIONS: The
      introduction of primary care policy reforms coincided with an increase in short
      stay admission rates for children with primary care-sensitive chronic conditions,
      and with more children being admitted through emergency departments. Short-stay
      admission rates for primary care-sensitive infectious illness increased more
      steadily and could be related to lowered thresholds for hospital admission.

PMID- 25964397
TI  - More Comprehensive Care Among Family Physicians is Associated with Lower Costs
      and Fewer Hospitalizations.
AB  - PURPOSE: Comprehensiveness is lauded as 1 of the 5 core virtues of primary care,
      but its relationship with outcomes is unclear. We measured associations between
      variations in comprehensiveness of practice among family physicians and
      healthcare utilization and costs for their Medicare beneficiaries. METHODS: We
      merged data from 2011 Medicare Part A and B claims files for a complex random
      sample of family physicians engaged in direct patient care, including 100% of
      their claimed care of Medicare beneficiaries, with data reported by the same
      physicians during their participation in Maintenance of Certification for Family
      Physicians (MC-FP) between the years 2007 and 2011. We created a measure of
      comprehensiveness from mandatory self-reported survey items as part of MC-FP
      examination registration. We compared this measure to another derived from
      Medicare's Berenson-Eggers Type of Service (BETOS) codes. We then examined the
      association between the 2 measures of comprehensiveness and hospitalizations,
      Part B payments, and combined Part A and B payments. RESULTS: Our full family
      physician sample consists of 3,652 physicians providing the plurality of care to
      555,165 Medicare beneficiaries. Of these, 1,133 recertified between 2007 and 2011
      and cared for 185,044 beneficiaries. There was a modest correlation (0.30)
      between the BETOS and self-reported comprehensiveness measures. After adjusting
      for beneficiary and physician characteristics, increasing comprehensiveness was
      associated with lower total Medicare Part A and B costs and Part B costs alone,
      but not with hospitalizations; the association with spending was stronger for the
      BETOS measure than for the self-reported measure; higher BETOS scores
      significantly reduced the likelihood of a hospitalization. CONCLUSIONS:
      Increasing family physician comprehensiveness of care, especially as measured by
      claims measures, is associated with decreasing Medicare costs and
      hospitalizations. Payment and practice policies that enhance primary care
      comprehensiveness may help "bend the cost curve."

PMID- 25964399
TI  - Communication practices and antibiotic use for acute respiratory tract infections
      in children.
AB  - PURPOSE: This study examined relationships between provider communication
      practices, antibiotic prescribing, and parent care ratings during pediatric
      visits for acute respiratory tract infection (ARTI). METHODS: A cross-sectional
      study was conducted of 1,285 pediatric visits motivated by ARTI symptoms.
      Children were seen by 1 of 28 pediatric providers representing 10 practices in
      Seattle, Washington, between December 2007 and April 2009. Providers completed
      post-visit surveys reporting on children's presenting symptoms, physical
      examination findings, assigned diagnoses, and treatments prescribed. Parents
      completed post-visit surveys reporting on provider communication practices and
      care ratings for the visit. Multivariate analyses identified key predictors of
      prescribing antibiotics for ARTI and of parent visit ratings. RESULTS: Suggesting
      actions parents could take to reduce their child's symptoms (providing positive
      treatment recommendations) was associated with decreased risk of antibiotic
      prescribing whether done alone or in combination with negative treatment
      recommendations (ruling out the need for antibiotics) [adjusted risk ratio (aRR)
      0.48; 95% CI, 0.24-0.95; and aRR 0.15; 95% CI, 0.06-0.40, respectively]. Parents
      receiving combined positive and negative treatment recommendations were more
      likely to give the highest possible visit rating (aRR 1.16; 95% CI, 1.01-1.34).
      CONCLUSION: Combined use of positive and negative treatment recommendations may
      reduce the risk of antibiotic prescribing for children with viral ARTIs and at
      the same time improve visit ratings. With the growing threat of antibiotic
      resistance at the community and individual level, these communication techniques
      may assist frontline providers in helping to address this pervasive public health
      problem.

PMID- 25964400
TI  - Repeated depression screening during the first postpartum year.
AB  - PURPOSE: Postpartum depression (PPD) screening at 4 to 12 weeks' postpartum can
      improve outcomes for women when linked to in-practice management programs. The
      benefit of repeated PPD screening during the first year postpartum remains
      unclear. METHODS: We report a substudy of a large pragmatic trial of early PPD
      screening and practice management, the Translating Research into Practice for
      Postpartum Depression (TRIPPD) study. Outcome analyses were based on demographic
      information and Patient Health Questionnaire (PHQ-9) screening scores from
      questionnaires mailed to all enrolled women at baseline (4 to 12 weeks'
      postpartum) and again at 6 and at 12 months' postpartum. The main outcomes of
      this substudy were the 6- and 12-month rates of PHQ-9 scores that were 10 or
      greater for women whose baseline PHQ-9 scores were less than 10. Women whose
      scores were 10 or greater would be considered at high risk of PPD and appropriate
      for further evaluation. RESULTS: At 6 months, 134 (10.9%) of the 1,235 women who
      did not have PHQ-9 scores greater than 10 at baseline had elevated scores
      appropriate for further evaluation. At 12 months, 59 (6.1%) of the 969 women who
      did not have PHQ-9 scores greater than 10 at baseline or at 6 months had elevated
      scores. Together the 6- and 12-month repeated screenings identified 193 women at
      high risk of depression. This finding represents 13.5% of the 1,432 women whose
      screening results were negative for PPD at baseline. CONCLUSIONS: Repeated PPD
      screening at 6 and 12 months' postpartum increases the percentage of women
      identified as being at high risk of PPD. Further work will be required to
      understand the impact of this repeated screening on patient outcomes.

PMID- 25964401
TI  - Working under a clinic-level quality incentive: primary care clinicians'
      perceptions.
AB  - BACKGROUND: A key consideration in designing pay-for-performance programs is
      determining what entity the incentive should be awarded to-individual clinicians
      or to groups of clinicians working in teams. Some argue that team-level
      incentives, in which clinicians who are part of a team receive the same incentive
      based on the team's performance, are most effective; others argue for the
      efficacy of clinician-level incentives. This study examines primary care
      clinicians' perceptions of a team-based quality incentive awarded at the clinic
      level. METHODS: This research was conducted with Fairview Health Services, where
      40% of the primary care compensation model was based on clinic-level quality
      performance. We conducted 48 in-depth interviews to explore clinicians'
      perceptions of the clinic-level incentive, as well as an online survey of 150
      clinicians (response rate 56%) to investigate which entity the clinicians would
      consider optimal to target for quality incentives. RESULTS: Clinicians reported
      the strengths of the clinic-based quality incentive were quality improvement for
      the team and less patient "dumping," or shifting patients with poor outcomes to
      other clinicians. The weaknesses were clinicians' lack of control and colleagues
      riding the coattails of higher performers. There were mixed reports on the
      model's impact on team dynamics. Although clinicians reported greater interaction
      with colleagues, some described an increase in tension. Most clinicians surveyed
      (73%) believed that there should be a mix of clinic and individual-level
      incentives to maintain collaboration and recognize individual performance.
      CONCLUSION: The study highlights the important advantages and disadvantages of
      using incentives based upon clinic-level performance. Future research should test
      whether hybrid incentives that mix group and individual incentives can maintain
      some of the best elements of each design while mitigating the negative impacts.

PMID- 25964402
TI  - Diagnostic invasiveness and psychosocial consequences of false-positive
      mammography.
AB  - PURPOSE: We undertook a study to assess whether women with false-positive
      mammography have worse psychosocial consequences if managed with a workup that
      involves a biopsy (invasive group) than if managed with only additional imaging
      (noninvasive group). METHODS: We performed subgroup analysis of a cohort study of
      454 women with abnormal screening mammography and 908 matched control women with
      normal results. Using a condition-specific questionnaire (Consequences of
      Screening in Breast Cancer), we assessed 12 psychosocial consequences at 5 time
      points (0, 1, 6, 18, and 36 months after final diagnosis) and compared the 2
      groups of women with false-positives (invasive and noninvasive management
      groups). RESULTS: Among the 252 women with false-positive mammography eligible
      for this study, psychosocial consequences were similar for those managed
      invasively and those managed noninvasively during the 36 months of follow-up. In
      60 comparisons (12 scales and 5 time points), differences between the groups were
      never statistically significant (P <.01) and the point estimates for the
      differences were always close to zero. The psychosocial consequences of women
      with false-positive results, regardless of management, fell between those of
      women with normal mammography and those of women determined to have breast
      cancer. CONCLUSIONS: We found no evidence that use of more invasive diagnostics
      was associated with worse psychosocial consequences. It is therefore reasonable
      to pool subgroups of women with false-positives in a single analysis. The
      invasiveness of subsequent diagnostic procedures does not help to identify women
      at higher risk for adverse psychosocial consequences of false-positive
      mammography.

PMID- 25964404
TI  - Recreational drug use among primary care patients: implications of a positive
      self-report.
AB  - Should recreational drug use raise clinical concern? We examined the association
      between weekend-only recreational drug use at baseline (yes vs no) and any
      increase in recreational drug use frequency or severity over 6 months among
      primary care patients who screen positive for drug use. In the weekend-only
      recreational drug use group (52/483 [10.8%]), 54% (28/52) started using drugs on
      weekdays. Compared with use not limited to weekends, weekend-only use was
      associated with lower odds of increasing drug use frequency (AOR 0.48, P = 0.03)
      and lower odds (non-significant) of increasing severity (AOR 0.56, P = 0.07).
      Although weekend-only recreational drug use appears prognostically less severe,
      the findings nonetheless suggest that continued episodic monitoring may be
      clinically wise. 

PMID- 25964403
TI  - Health IT-Enabled Care Coordination: A National Survey of Patient-Centered
      Medical Home Clinicians.
AB  - PURPOSE: Health information technology (IT) offers promising tools for improving
      care coordination. We assessed the feasibility and acceptability of 6 proposed
      care coordination objectives for stage 3 of the Centers for Medicare and Medicaid
      Services electronic health record incentive program (Meaningful Use) related to
      referrals, notification of care from other facilities, patient clinical
      summaries, and patient dashboards. METHODS: We surveyed physician-owned and
      hospital/health system-affiliated primary care practices that achieved patient
      centered medical home recognition and participated in the Meaningful Use program,
      and community health clinics with patient-centered medical home recognition (most
      with certified electronic health record systems). The response rate was 35.1%. We
      ascertained whether practices had implemented proposed objectives and perceptions
      of their importance. We analyzed the association of organizational and contextual
      factors with self-reported use of health IT to support care coordination
      activities. RESULTS: Although 78% of the 350 respondents viewed timely
      notification of hospital discharges as very important, only 48.7% used health IT
      systems to accomplish this task. The activity most frequently supported by health
      IT was providing clinical summaries to patients, in 76.6% of practices; however,
      merely 47.7% considered this activity very important. Greater use of health IT to
      support care coordination activities was positively associated with the presence
      of a nonclinician responsible for care coordination and the practice's capacity
      for systematic change. CONCLUSIONS: Even among practices having a strong
      commitment to the medical home model, the use of health IT to support care
      coordination objectives is not consistent. Health IT capabilities are not
      currently aligned with clinicians' priorities. Many practices will need financial
      and technical assistance for health IT to enhance care coordination.

PMID- 25964405
TI  - SBIRT as a Vital Sign for Behavioral Health Identification, Diagnosis, and
      Referral in Community Health Care.
AB  - The purpose of this quasi-experimental design study was to examine the
      effectiveness of the behavioral health Screening, Brief Intervention, and
      Referral to Treatment (SBIRT) program at a community health center. The study
      group was twice as likely (25.3%) to have depression and substance abuse
      diagnosed compared with the control group (11.4%) (P <.001). Referral rates for
      the study group were more likely to occur (12.4%) compared with referral rates
      for the control group (1.0%) (P <.001); however, the kept appointment rates by
      patients for behavioral health problems referrals remained low for both groups.
      SBIRT was effectively utilized in a community health center, resulting in
      increased rates for diagnosis of behavioral health problems and referrals of
      patients. 

PMID- 25964406
TI  - Measuring Physician Quality and Efficiency in an Era of Practice Transformation:
      PCMH as a Case Study.
AB  - Practicing physicians face myriad challenges as health care undergoes
      considerable transformation, including advancing efforts to measure and report on
      physician quality and efficiency, as well as the growth of new care models such
      as Accountable Care Organizations and patient-centered medical homes (PCMHs). How
      do these transformational forces relate to one another? How should practicing
      physicians focus and prioritize their improvement efforts? This Special Report
      examines how physicians' performance on quality and efficiency measures may
      interact with delivery reforms, focusing on the PCMH. We note that although the
      PCMH is a promising model, published evidence is mixed. Using data and experience
      from a large commercial insurer's performance transparency and PCMH programs, we
      further report that longitudinal analysis of UnitedHealthcare's PCMH program
      experience has shown favorable changes; however, cross-sectional analysis
      indicates that National Committee for Quality Assurance's PCMH designation is
      positively associated with achieving program Quality benchmarks, but negatively
      associated with program Efficiency benchmarks. This example illustrates some key
      issues for physicians in the current environment, and we provide suggestions for
      physicians and other stakeholders on understanding and acting on information from
      physician performance measurement programs. 

PMID- 25964407
TI  - The Dissenter's Viewpoint: There Has to Be a Better Way to Measure a Medical
      Home.
AB  - The patient-centered medical home (PCMH) is widely touted as the current pathway
      to high-quality primary care practice. Many payers and institutions are using the
      formal National Committee for Quality Assurance (NCQA) PCMH tool to evaluate
      practices. Practices commonly feel pressured financially to achieve NCQA
      recognition. As 2 small high-functioning innovative primary care practices, we
      describe the actual process of using this tool and assess its utility using a
      framework based on patient experience of care, costs, and population health. We
      both attained certification as Level 3 PCMHs but conclude that NCQA's tool
      mismatches form and function, is costly and wasteful, and may succeed more in
      documentation of policies than in supporting improved outcomes in practices. 

PMID- 25964408
TI  - When practice transformation impedes practice improvement.
AB  - I lead a small practice in rural western North Carolina. We have embraced the
      patient-centered medical home model and other practice-improvement initiatives,
      and I have seen our practice transformed in many positive ways. But in the past
      year alone, my staff and I have spent hundreds of hours studying for and taking
      exams, certifying for numerous programs, and updating our electronic health
      records system (EHR) to meet new national requirements and then relearning our
      EHR. Seeing patients used to be the hardest part of my job. It is now the easiest
      by far. I am considering walking away from the time-intensive PCMH certification
      even though it would cause financial hardship. We have more important business at
      hand-taking excellent care of patients, improving our practice, and meaningfully
      engaging with our patients. 

PMID- 25964409
TI  - ABCDE in Clinical Encounters: Presentations of Self in Doctor-Patient
      Communication.
AB  - Professional discussions about communication in medical settings often ignore the
      various personal identities that doctors and patients bring to their clinical
      encounters. From my 26 years as a family physician, and informed by literature
      from other professional disciplines, I propose an alternate understanding: to
      think of doctors and patients as a collection of individual identities, each
      formed by a discrete presentation of self. I describe how at least 5 important
      presentations of self arise in clinical encounters, including those relating to
      meaning, community, agency, anxiety, and organism. I frame these presentations of
      self with the mnemonic ABCDE, briefly review key dimensions of each, and suggest
      how physicians can reflect on these dimensions in order to find equilibrium in
      their interactions with patients. Lastly, I submit that finding this balance can
      reduce relational challenges with patients and enhance the therapeutic
      effectiveness of doctor-patient communication. 

PMID- 25964410
TI  - One cold autumn day.
AB  - Behavioral change is at the heart of effective primary care, but when patients
      don't change, how do we account for our days? In this personal essay, I relate an
      encounter with a patient who wants to quit smoking, lose weight, and control her
      diabetes. I am discouraged when she deflects my recommendations, but a
      colleague's comment encourages a deeper inquiry. Knowing the patient's story and
      deepening the conversation, however, do not guarantee change. The experience
      reminds me why patience, humility, and faith are core values of the primary care
      physician. 

PMID- 25964411
TI  - Smiling toothless.
AB  - In an impoverished outreach clinic in Beirut, a young boy's unique thank you
      answers a physician's questions about the meaning of her profession. 

PMID- 25964412
TI  - Evolving competencies for chairs of departments of family medicine.

PMID- 25964413
TI  - The Council of Academic Family Medicine procedural and maternity care training
      guidelines: a better path to consistency in competency assessment in family
      medicine.

PMID- 25964415
TI  - AAFP celebrates new recruits to family medicine, acknowledges work ahead.

PMID- 25964416
TI  - ABFM to simplify MOC for family physicians and make it more meaningful: a family
      medicine registry.

PMID- 25964419
TI  - Dual foraging and pair coordination during chick provisioning by Manx
      shearwaters: empirical evidence supported by a simple model.
AB  - The optimal allocation of time and energy between one's own survival and
      offspring survival is critical for iteroparous animals, but creates a conflict
      between what maximises the parent's fitness and what maximises fitness of the
      offspring. For central-place foragers, provisioning strategies may reflect this
      allocation, while the distance between central-places and foraging areas may
      influence the decision. Nevertheless, few studies have explored the link between
      life history and foraging in the context of resource allocation. Studying
      foraging behaviour alongside food load rates to chicks provides a useful system
      for understanding the foraging decisions made during parent-offspring conflict.
      Using simultaneously deployed GPS and time-depth recorders, we examined the
      provisioning strategies in free-living Manx shearwaters Puffinus puffinus, which
      were caring for young. Our results showed a bimodal pattern, where birds
      alternate short and long trips. Short trips were associated with higher feeding
      frequency and larger meals than long trips, suggesting that long trips were
      performed for self-feeding. Furthermore, most foraging was carried out within 100
      km of sea fronts. A simple model based on patch quality and travel time shows
      that for Manx shearwaters combining chick feeding and self-maintenance, bimodal
      foraging trip durations optimise feeding rates. 

PMID- 25964420
TI  - Oxygen-limited thermal tolerance is seen in a plastron-breathing insect and can
      be induced in a bimodal gas exchanger.
AB  - Thermal tolerance has been hypothesized to result from a mismatch between oxygen
      supply and demand. However, the generality of this hypothesis has been challenged
      by studies on various animal groups, including air-breathing adult insects.
      Recently, comparisons across taxa have suggested that differences in gas exchange
      mechanisms could reconcile the discrepancies found in previous studies. Here, we
      test this suggestion by comparing the behaviour of related insect taxa with
      different gas exchange mechanisms, with and without access to air. We demonstrate
      oxygen-limited thermal tolerance in air-breathing adults of the plastron
      exchanging water bug Aphelocheirus aestivalis. Ilyocoris cimicoides, a related,
      bimodal gas exchanger, did not exhibit such oxygen-limited thermal tolerance and
      relied increasingly on aerial gas exchange with warming. Intriguingly, however,
      when denied access to air, oxygen-limited thermal tolerance could also be induced
      in this species. Patterns in oxygen-limited thermal tolerance were found to be
      consistent across life-history stages in these insects, with nymphs employing the
      same gas exchange mechanisms as adults. These results advance our understanding
      of oxygen limitation at high temperatures; differences in the degree of
      respiratory control appear to modulate the importance of oxygen in setting
      tolerance limits. 

PMID- 25964421
TI  - Is oxidative status influenced by dietary carotenoid and physical activity after
      moult in the great tit (Parus major)?
AB  - In the context of sexual and natural selection, an allocation trade-off for
      carotenoid pigments may exist because of their obligate dietary origin and their
      role both in the antioxidant and immune systems and in the production of coloured
      signals in various taxa, particularly birds. When birds have expended large
      amounts of carotenoids to feather growth such as after autumn moult, bird health
      and oxidative status might be more constrained. We tested this hypothesis in a
      bird species with carotenoid-based plumage colour, by manipulating dietary
      carotenoids and physical activity, which can decrease antioxidant capacity and
      increase reactive oxygen metabolite (ROM) concentration. Great tits were captured
      after moult and kept in aviaries, under three treatments: physical handicap and
      dietary supplementation with carotenoids, physical handicap and control diet, and
      no handicap and control diet. We measured plasma composition (antioxidant
      capacity, ROM concentration, and vitamin A, vitamin E and total carotenoid
      concentrations), immune system activation (blood sedimentation) and stress
      response (heterophil/lymphocyte ratio) and predicted that handicap treatment
      should influence these negatively and carotenoid supplementation positively.
      Coloration of yellow feathers was also measured. Carotenoid supplementation
      increased total plasma carotenoid concentration, decreased feather carotenoid
      chroma and marginally increased ROM concentration. Handicap increased blood
      sedimentation only in males but had no clear influence on oxidative stress, which
      contradicted previous studies. Further studies are needed to investigate how
      physical activity and carotenoid availability might interact and influence
      oxidative stress outside the moult period, and their combined potential influence
      on attractiveness and reproductive investment later during the breeding season. 

PMID- 25964422
TI  - Ultraviolet filters in stomatopod crustaceans: diversity, ecology and evolution.
AB  - Stomatopod crustaceans employ unique ultraviolet (UV) optical filters in order to
      tune the spectral sensitivities of their UV-sensitive photoreceptors. In the
      stomatopod species Neogonodactylus oerstedii, we previously found four filter
      types, produced by five distinct mycosporine-like amino acid pigments in the
      crystalline cones of their specialized midband ommatidial facets. This UV
      spectral tuning array produces receptors with at least six distinct spectral
      sensitivities, despite expressing only two visual pigments. Here, we present a
      broad survey of these UV filters across the stomatopod order, examining their
      spectral absorption properties in 21 species from seven families in four
      superfamilies. We found that UV filters are present in three of the four
      superfamilies, and evolutionary character reconstruction implies that at least
      one class of UV filter was present in the ancestor of all modern stomatopods.
      Additionally, postlarval stomatopods were observed to produce the UV filters
      simultaneously alongside development of the adult eye. The absorbance properties
      of the filters are consistent within a species; however, between species we found
      a great deal of diversity, both in the number of filters and in their spectral
      absorbance characteristics. This diversity correlates with the habitat depth
      ranges of these species, suggesting that species living in shallow, UV-rich
      environments may tune their UV spectral sensitivities more aggressively. We also
      found additional, previously unrecognized UV filter types in the crystalline
      cones of the peripheral eye regions of some species, indicating the possibility
      for even greater stomatopod visual complexity than previously thought. 

PMID- 25964423
TI  - Muscle force, work and cost: a novel technique to revisit the Fenn effect.
AB  - Muscle produces force by forming cross-bridges, using energy released from ATP.
      While the magnitude and duration of force production primarily determine the
      energy requirement, nearly a century ago Fenn observed that muscle shortening or
      lengthening influenced energetic cost of contraction. When work is done by the
      muscle, the energy cost is increased and when work is done on the muscle the
      energy cost is reduced. However, the magnitude of the 'Fenn effect' and its
      mirror ('negative Fenn effect') have not been quantitatively resolved. We
      describe a new technique coupling magnetic resonance spectroscopy with an in vivo
      force clamp that can directly quantify the Fenn effect [E=I+W, energy liberated
      (E) equals the energy cost of isometric force production (I) plus the work done
      (W)] and the negative Fenn effect (E=I-W) for one muscle, the first dorsal
      interosseous (FDI). ATP cost was measured during a series of contractions, each
      of which occurred at a constant force and for a constant duration, thus constant
      force-time integral (FTI). In all subjects, as the FTI increased with load, there
      was a proportional linear increase in energy cost. In addition, the cost of
      producing force greatly increased when the muscle shortened, and was slightly
      reduced during lengthening contraction. These results, though limited to a single
      muscle, contraction velocity and muscle length change, do quantitatively support
      the Fenn effect. We speculate that they also suggest that an elastic element
      within the FDI muscle functions to preserve the force generated within the cross
      bridges. 

PMID- 25964424
TI  - Fractional clearance for verapamil N-demethylation in the isolated rat liver
      preparation.

PMID- 25964425
TI  - Response to letter to the editor on "fractional clearance for verapamil N
      demethylation in the isolated rat liver preparation".

PMID- 25964426
TI  - Clonally related uterine leiomyomas are common and display branched tumor
      evolution.
AB  - Uterine leiomyomas are extremely frequent benign smooth muscle tumors often
      presenting as multiple concurrent lesions and causing symptoms such as abnormal
      menstrual bleeding, abdominal pain and infertility. While most leiomyomas are
      believed to arise independently, a few studies have encountered separate lesions
      harboring identical genetic changes, suggesting a common clonal origin. To
      investigate the frequency of clonally related leiomyomas, genome-wide tools need
      to be utilized, and thus little is known about this phenomenon. Using MED12
      sequencing and SNP arrays, we searched for clonally related uterine leiomyomas in
      a set of 103 tumors from 14 consecutive patients who entered hysterectomy owing
      to symptomatic lesions. Whole-genome sequencing was also utilized to study the
      genomic architecture of clonally related tumors. This revealed four patients to
      have two or more tumors that were clonally related, all of which lacked MED12
      mutations. Furthermore, some tumors were composed of genetically distinct
      subclones, indicating a nonlinear, branched model of tumor evolution. DEPDC5 was
      discovered as a novel tumor suppressor gene playing a role in the progression of
      uterine leiomyomas. Perhaps counterintuitively-considering Knudson's two-hit
      hypothesis-a large shared deletion was followed by different truncating DEPDC5
      mutations in four clonally related leiomyomas. This study provides insight into
      the intratumor heterogeneity of these tumors and suggests that a shared clonal
      origin is a common feature of leiomyomas that do not carry an MED12 mutation.
      These observations also offer one explanation to the common occurrence of
      multiple concurrent lesions.

PMID- 25964427
TI  - Mitochondrial DNA variants can mediate methylation status of inflammation,
      angiogenesis and signaling genes.
AB  - Mitochondrial (mt) DNA can be classified into haplogroups representing different
      geographic and/or racial origins of populations. The H haplogroup is protective
      against age-related macular degeneration (AMD), while the J haplogroup is high
      risk for AMD. In the present study, we performed comparison analyses of human
      retinal cell cybrids, which possess identical nuclei, but mtDNA from subjects
      with either the H or J haplogroups, and demonstrate differences in total global
      methylation, and expression patterns for two genes related to acetylation and
      five genes related to methylation. Analyses revealed that untreated-H and -J
      cybrids have different expression levels for nuclear genes (CFH, EFEMP1, VEGFA
      and NFkB2). However, expression levels for these genes become equivalent after
      treatment with a methylation inhibitor, 5-aza-2'-deoxycytidine. Moreover,
      sequencing of the entire mtDNA suggests that differences in epigenetic status
      found in cybrids are likely due to single nucleotide polymorphisms (SNPs) within
      the haplogroup profiles rather than rare variants or private SNPs. In conclusion,
      our findings indicate that mtDNA variants can mediate methylation profiles and
      transcription for inflammation, angiogenesis and various signaling pathways,
      which are important in several common diseases. 

PMID- 25964428
TI  - Systemic AAV9 gene transfer in adult GM1 gangliosidosis mice reduces lysosomal
      storage in CNS and extends lifespan.
AB  - GM1 gangliosidosis (GM1) is an autosomal recessive lysosomal storage disease
      where GLB1 gene mutations result in a reduction or absence of lysosomal acid beta
      galactosidase (betagal) activity. betagal deficiency leads to accumulation of GM1
      ganglioside in the central nervous system (CNS). GM1 is characterized by
      progressive neurological decline resulting in generalized paralysis, extreme
      emaciation and death. In this study, we assessed the therapeutic efficacy of an
      adeno-associated virus (AAV) 9-mbetagal vector infused systemically in adult GM1
      mice (betaGal(-/-)) at 1 * 10(11) or 3 * 10(11) vector genomes (vg). Biochemical
      analysis of AAV9-treated GM1 mice showed high betaGal activity in liver and
      serum. Moderate betaGal levels throughout CNS resulted in a 36-76% reduction in
      GM1-ganglioside content in the brain and 75-86% in the spinal cord. Histological
      analyses of the CNS of animals treated with 3 * 10(11) vg dose revealed increased
      presence of betagal and clearance of lysosomal storage throughout cortex,
      hippocampus, brainstem and spinal cord. Storage reduction in these regions was
      accompanied by a marked decrease in astrogliosis. AAV9 treatment resulted in
      improved performance in multiple tests of motor function and behavior. Also the
      majority of GM1 mice in the 3 * 10(11) vg cohort retained ambulation and rearing
      despite reaching the humane endpoint due to weight loss. Importantly, the median
      survival of AAV9 treatment groups (316-576 days) was significantly increased over
      controls (250-264 days). This study shows that moderate widespread expression of
      betagal in the CNS of GM1 gangliosidosis mice is sufficient to achieve
      significant biochemical impact with phenotypic amelioration and extension in
      lifespan. 

PMID- 25964429
TI  - Serum human trefoil factor 3 is a biomarker for mucosal healing in ulcerative
      colitis patients with minimal disease activity.
AB  - BACKGROUND: The goals of treating ulcerative colitis (UC) have shifted from
      clinical remission to mucosal healing. Non-invasive biomarkers are required to
      assess mucosal healing as endoscopic assessment is inconvenient for patients.
      Enhanced expression of trefoil factor 3 (TFF3, a mucin-associated peptide) is
      observed after injury of the gastrointestinal tract. The present study was
      designed to evaluate TFF3 as a biomarker of mucosal healing in patients with UC.
      METHODS: This cross-sectional study included consecutive patients with UC (18-65
      years old, disease duration >3 months, either left-sided colitis or pancolitis)
      who had a Simple Clinical Colitis Activity Index (SCCAI) <6. Colonoscopy was done
      to assess the presence or absence of mucosal healing (defined using the Baron
      score) in all patients. Serum level of TFF3 was assessed in all patients and 20
      healthy controls. RESULTS: Seventy-four patients were included [mean age 37.2+/
      10.9 years, 47 males, median disease duration 4.8 years (IQR 3-8.3), median SCCAI
      = 0] in the study. Forty-three patients had mucosal healing (Baron score 0 or 1)
      and 31 did not (Baron score 2 or 3). Median TFF3 level in patients without
      mucosal healing was significantly higher than that in patients with mucosal
      healing [1.5 (IQR 1.2-1.9) vs 1.1 (IQR 0.8-1.3) ng/ml, p = 0.01] and healthy
      controls [0.85 (IQR 0.7-1.2) ng/ml, p < 0.001]. A serum TFF3 level of <1.27 ng/ml
      (as determined by the receiver operating characteristic curve; area under the
      curve 0.73) had sensitivity, specificity, positive predictive value and negative
      predictive value of 70, 68, 75 and 62%, respectively, for identifying patients
      with mucosal healing. CONCLUSION: Serum TFF3 can potentially be used as a
      biomarker to assess mucosal healing in UC patients.

PMID- 25964430
TI  - Activators of TRPM2: Getting it right.

PMID- 25964431
TI  - Dynamic phospholipid interaction of beta2e subunit regulates the gating of
      voltage-gated Ca2+ channels.
AB  - High voltage-activated Ca2+ (Ca(V)) channels are protein complexes containing
      pore-forming alpha1 and auxiliary beta and alpha2delta subunits. The subcellular
      localization and membrane interactions of the beta subunits play a crucial role
      in regulating Ca(V) channel inactivation and its lipid sensitivity. Here, we
      investigated the effects of membrane phosphoinositide (PI) turnover on Ca(V)2.2
      channel function. The beta2 isoform beta2e associates with the membrane through
      electrostatic and hydrophobic interactions. Using chimeric beta subunits and
      liposome-binding assays, we determined that interaction between the N-terminal 23
      amino acids of beta2e and anionic phospholipids was sufficient for beta2e
      membrane targeting. Binding of the beta2e subunit N terminus to liposomes was
      significantly increased by inclusion of 1% phosphatidylinositol 4,5-bisphosphate
      (PIP2) in the liposomes, suggesting that, in addition to phosphatidylserine, PIs
      are responsible for beta2e targeting to the plasma membrane. Membrane binding of
      the beta2e subunit slowed Ca(V)2.2 current inactivation. When membrane
      phosphatidylinositol 4-phosphate and PIP2 were depleted by rapamycin-induced
      translocation of pseudojanin to the membrane, however, channel opening was
      decreased and fast inactivation of Ca(V)2.2(beta2e) currents was enhanced.
      Activation of the M1 muscarinic receptor elicited transient and reversible
      translocation of beta2e subunits from membrane to cytosol, but not that of beta2a
      or beta3, resulting in fast inactivation of Ca(V)2.2 channels with beta2e. These
      results suggest that membrane targeting of the beta2e subunit, which is mediated
      by nonspecific electrostatic insertion, is dynamically regulated by receptor
      stimulation, and that the reversible association of beta2e with membrane PIs
      results in functional changes in Ca(V) channel gating. The phospholipid-protein
      interaction observed here provides structural insight into mechanisms of membrane
      protein association and the role of phospholipids in ion channel regulation.

PMID- 25964432
TI  - Glycine-dependent activation of NMDA receptors.
AB  - N-methyl-d-aspartate (NMDA) receptors are the only neurotransmitter receptors
      whose activation requires two distinct agonists. Heterotetramers of two GluN1 and
      two GluN2 subunits, NMDA receptors are broadly distributed in the central nervous
      system, where they mediate excitatory currents in response to synaptic glutamate
      release. Pore opening depends on the concurrent presence of glycine, which
      modulates the amplitude and time course of the glutamate-elicited response.
      Gating schemes for fully glutamate- and glycine-bound NMDA receptors have been
      described in sufficient detail to bridge the gap between microscopic and
      macroscopic receptor behaviors; for several receptor isoforms, these schemes
      include glutamate-binding steps. We examined currents recorded from cell-attached
      patches containing one GluN1/GluN2A receptor in the presence of several glycine
      site agonists and used kinetic modeling of these data to develop reaction schemes
      that include explicit glycine-binding steps. Based on the ability to match a
      series of experimentally observed macroscopic behaviors, we propose a model for
      activation of the glutamate-bound NMDA receptor by glycine that predicts apparent
      negative agonist cooperativity and glycine-dependent desensitization in the
      absence of changes in microscopic binding or desensitization rate constants.
      These results complete the basic steps of an NMDA receptor reaction scheme for
      the GluN1/GluN2A isoform and prompt a reevaluation of how glycine controls NMDA
      receptor activation. We anticipate that our model will provide a useful
      quantitative instrument to further probe mechanisms and structure-function
      relationships of NMDA receptors and to better understand the physiological and
      pathological implications of endogenous fluctuations in extracellular glycine
      concentrations. 

PMID- 25964434
TI  - Anatomical features of the vertebral artery for transbrachial direct cannulation
      of a guiding catheter to perform coil embolization of cerebral aneurysms in the
      posterior cerebral circulation.
AB  - BACKGROUND: Transbrachial approach is an alternative technique for coil
      embolization of posterior circulation aneurysms. The purpose of our study was to
      investigate the anatomical features of the vertebral artery (VA) for
      transbrachial direct VA cannulation of a guiding catheter (GC) to perform coil
      embolization of posterior circulation aneurysms. METHODS: Included in
      retrospective analysis were patients who underwent transbrachial coil
      embolization of cerebral aneurysms in the posterior cerebral circulation by
      direct VA cannulation of a GC from 2007 to 2013. Investigated were patient
      characteristics, preoperative sizes of aneurysms, aneurysms location, the angle
      formed by the target VA and the subclavian artery (AVS), and the VA diameter at
      the level of the fourth cervical vertebral body (VAD) in the side of the
      transbrachial access route. RESULTS: Thirty-one patients with 32 aneurysms met
      our criteria. The locations of aneurysms were the VA (n = 16), basilar artery
      (BA) tip (n = 10), BA trunk (n = 3), BA superior cerebellar artery (n = 1), BA
      anterior inferior cerebellar artery (n = 1), and VA posterior inferior cerebellar
      artery (n = 1). The right brachial artery was punctured in 27 cases with 28
      aneurysms as transbrachial direct cannulation of a GC, and left was in 4 cases
      with 4 aneurysms. The average AVS, ranging from 45 degrees  to 95 degrees , was
      77 degrees , and the average VAD, ranging from 3.18 to 4.45 mm, was 3.97 mm.
      CONCLUSION: For transbrachial direct cannulation of a GC, it seems required that
      the AVS is about 45 degrees  or more and the VAD is about 3.18 mm or more.

PMID- 25964433
TI  - The stress response neuropeptide CRF increases amyloid-beta production by
      regulating gamma-secretase activity.
AB  - The biological underpinnings linking stress to Alzheimer's disease (AD) risk are
      poorly understood. We investigated how corticotrophin releasing factor (CRF), a
      critical stress response mediator, influences amyloid-beta (Abeta) production. In
      cells, CRF treatment increases Abeta production and triggers CRF receptor 1
      (CRFR1) and gamma-secretase internalization. Co-immunoprecipitation studies
      establish that gamma-secretase associates with CRFR1; this is mediated by beta
      arrestin binding motifs. Additionally, CRFR1 and gamma-secretase co-localize in
      lipid raft fractions, with increased gamma-secretase accumulation upon CRF
      treatment. CRF treatment also increases gamma-secretase activity in vitro,
      revealing a second, receptor-independent mechanism of action. CRF is the first
      endogenous neuropeptide that can be shown to directly modulate gamma-secretase
      activity. Unexpectedly, CRFR1 antagonists also increased Abeta. These data
      collectively link CRF to increased Abeta through gamma-secretase and provide
      mechanistic insight into how stress may increase AD risk. They also suggest that
      direct targeting of CRF might be necessary to effectively modulate this pathway
      for therapeutic benefit in AD, as CRFR1 antagonists increase Abeta and in some
      cases preferentially increase Abeta42 via complex effects on gamma-secretase. 

PMID- 25964435
TI  - Neurovascular reconstruction with flow diverter stents for the treatment of 87
      intracranial aneurysms: Clinical results.
AB  - BACKGROUND: Flow diverter stents represent a new endovascular tool to treat
      complex aneurysms, such as giant, large, wide-necked and fusiform. The highly
      dense mash of these stents reduces inflow and outflow inside the aneurysm,
      resulting in intra aneurysmal thrombosis and stent endothelialization.
      OBJECTIVES: To present the results of treatment of intracranial aneurysms with
      flow diverter stents in a single center. METHODS: Retrospective review of 77
      patients with 87 aneurysms treated using two different types of flow diverter
      stent, the Pipeline Embolization Device and SILK stent, between October 2010 and
      September 2013 in an interventional neuroradiology center. RESULTS: Flow diverter
      stent placement was successful in 98% of the lesions and resulted in an immediate
      major stasis within most of the treated aneurysms. The overall aneurysm occlusion
      rate at six months and 18 months was 80% and 84% respectively. Symptomatic
      complications occurred in 11 patients (14.3%) with morbidity in eight (10.4%) and
      mortality in three patients (3.9%). CONCLUSION: Flow diversion is a promising
      technique for treatment of challenging intracranial aneurysms with acceptable
      morbidity. A high rate of complete occlusion for small large necked aneurysms, a
      low morbidity and mortality rate and no recanalization encourage their use in
      these aneurysms. Further studies accessing long-term aneurysm occlusion and
      recanalization are required.

PMID- 25964437
TI  - Very late in-stent thrombosis 9 years after double stent treatment of fusiform
      basilar artery aneurysm.
AB  - Endovascular treatment seems to be the best approach to posterior circulation
      fusiform aneurysms. Double stent techniques are frequently used to occlude
      basilar artery dilations. Unfortunately, there is a limited number of studies
      that have followed up with patients over prolonged periods of time in order to
      evaluate delayed complications, such as stenosis, thrombosis or migration of
      stents. We present an unusual case of in-stent thrombosis 9 years after basilar
      artery aneurysm treatment to caution about complications associated with double
      stent implantation. 

PMID- 25964436
TI  - Safety of Abciximab injection during endovascular treatment of ruptured
      aneurysms.
AB  - BACKGROUND AND PURPOSE: We aimed to determine the safety of intra-arterial
      Abciximab injection in the management of thromboembolic complications during
      endovascular treatment of ruptured cerebral aneurysms. METHODS: In a monocentric
      consecutive series of endovascular treatment of 783 ruptured aneurysms, 42 (5.3%)
      patients received Abciximab after the aneurysm was secured. Bleeding
      complications were registered and dichotomized as follows: new intracranial
      hemorrhage and peripheral bleeding. For each patient, World Federation of
      Neurosurgery (WFNS) subarachnoid hemorrhage (SAH) grade, shunting, and clinical
      outcomes in the post-operative period and at 3-6 months were recorded. RESULTS:
      SAH WFNS grades were as follows: grade I n = 14, grade II n = 10, grade III n =
      11, grade IV n = 4, grade V n = 3. Ten patients had intracranial hematoma
      additionally to the SAH prior to embolization. Four patients (9.5%) presented
      more blood on the post-embolization CT but only one suffered a new clinically
      relevant intracranial hemorrhage. Two patients (4.8%) experienced significant
      peripheral bleeding but none were associated with long-term disabilities.
      Fourteen patients had a shunt installed less than 24 h prior to Abciximab
      injection and one less than 48 h later. At 3-6-month follow-up, 31 patients (74%)
      achieved a modified Rankin Scale score (mRS) of 2 or less, six patients (14%) had
      a mRS of 3-5, three were dead (7%), and two were lost at follow-up. CONCLUSION:
      When the aneurysm is secured, intra-arterial Abciximab injection is a low
      complication rate treatment modality for thromboembolic events during
      embolization of cerebral ruptured aneurysm.

PMID- 25964438
TI  - AngiosealTM as a hemostatic device for direct carotid puncture during
      endovascular procedures.
AB  - INTRODUCTION: Direct carotid artery puncture (DCP) is employed in patients with
      tortuous anatomy and peripheral vascular disease when the peripheral arteries are
      not available for vascular access. Manual compression is the only method of
      achieving hemostasis following DCP and, till date, the use of a closure device
      for DCP has been reported in only one patient. In this study we sought to analyze
      our experience with the use of closure device for DCP. METHODS: This is a
      retrospective study of patients in whom AngiosealTM was used following DCP for
      neuroendovascular procedures. Medical charts and imaging of these patients was
      reviewed for any abnormalities pertaining to the use of the closure device.
      RESULTS: A total of eight patients were included in the study. AngiosealTM was
      used in all the patients. There were no complications related to the use of the
      closure device in any of the eight patients. Immediate post-procedure angiography
      done in one patient did not show any structural or hemodynamic abnormalities
      within the carotid artery lumen. At 6 months follow-up imaging, there was no
      evidence stenosis or vascular wall abnormality in any of the patients. There were
      no adverse clinical reactions related to the use of closure device. CONCLUSION:
      In our experience, AngiosealTM may be a safe and off-label effective closure
      device for patients undergoing DCP for neuroendovascular procedures. It obviates
      the need for manual compression without causing any structural or hemodynamic
      changes within the carotid artery. Larger studies with longer follow-up are
      required to establish its safety in patients undergoing DCP.

PMID- 25964439
TI  - Rare use of twin Solitaire(r) stents in the double waffle-cone technique for
      endovascular treatment of a wide-necked bifurcation aneurysm.
AB  - Endovascular treatment of wide-necked bifurcation aneurysms may be challenging.
      The waffle-cone technique can be used in these aneurysms in case of acute
      angulation between parent artery and distal artery of the aneurysm. Solitaire(r)
      stent (Ev3, Irvine, CA, USA) has the significant advantage of mitigating the
      potential complication risks. This study reports the second case in the
      literature in which endovascular treatment of a wide-necked bifurcation aneurysm
      with the double waffle-cone technique by using twin Solitaire(r) stents proved to
      be successful. 

PMID- 25964440
TI  - Spontaneous thrombosis of the main draining vein revealing an unruptured brain
      arteriovenous malformation.
AB  - Haemorrhage is the most frequent revealing condition of brain arteriovenous
      malformations (bAVMs). We report a rare case of unruptured parietal bAVM revealed
      by spontaneous thrombosis of the main draining vein, responsible for a focal
      neurological deficit. The bAVM was embolized in emergency conditions; complete
      regression of the neurological symptoms was observed within five days after the
      embolization. Potential mechanisms of such spontaneous thrombosis of the bAVM's
      main drainage pathway as well as an exhaustive review of the literature
      concerning this rare revealing condition are presented and discussed. 

PMID- 25964441
TI  - Current trends in mini-invasive management of spine metastases.
AB  - The spine is a frequent localization of primary tumours or metastasis involving
      posterior arch, pedicles and vertebra body, and often causing unsustainable pain.
      The management of spinal metastasis remains complex, including medical therapy
      (corticosteroids, chemotherapy), radiotherapy and surgical treatment, or the
      recent percutaneous mini-invasive approach. The target of all these treatments is
      to improve the quality of life of patients affected by this type of lesion.
      Diagnosis of spinal metastasis and then its treatment should be based on the
      combination of different elements: clinical evaluation, CT, MRI and nuclear
      medicine patterns, considering the age of the patient, known primary tumour,
      location of the lesions, single/multiple lesions, pattern of morphology (border,
      matrix, expansile character, soft tissue extension), density or signal intensity,
      oncologic instability and expectancy of life. The percutaneous mini-invasive
      approach for patients affected by secondary lesions involving the spine has as
      treatment goal of: (1) pain relief improving the quality of life; (2) stability
      treatment re-establishing the spinal biomechanics, alterated by bone destruction
      or deformity, preventing pathological fracture; and (3) an anti-neoplastic
      effect. The aim of this paper is to provide a comprehensive diagnostic and
      percutaneous approach to the bone metastatic spine lesions, identifying which
      metamer should be treated to improve patient quality of life, showing the
      importance of a multi-disciplinary approach to this problem. 

PMID- 25964442
TI  - Retrograde leptomeningeal venous approach for dural arteriovenous fistulas at
      foramen magnum.
AB  - A 72-year-old man presented with sudden right homonymous hemianopsia. Work-up
      imaging revealed a left occipital haematoma and an arteriovenous fistula supplied
      by the meningeal branches to the clivus from the left vertebral artery (VA) with
      a rostral venous reflux into cortical veins. A microcatheter was advanced through
      brainstem veins into the venous collector. A compliant balloon was placed in the
      left VA facing the origin of feeders. The balloon was inflated to protect the
      vertebrobasilar circulation from embolic migration. Onyx was injected by the
      transvenous catheter. Control angiogram revealed exclusion of the lesion.
      Informed consent was obtained from the patient. 

PMID- 25964443
TI  - Risk factors for coil protrusion into the parent artery and associated thrombo
      embolic events following unruptured cerebral aneurysm embolization.
AB  - OBJECTIVE: Advances in vascular reconstruction devices and coil technologies have
      made coil embolization a popular and effective strategy for treatment of
      relatively wide-neck cerebral aneurysms. However, coil protrusion occurs
      occasionally, and little is known about the frequency, the risk factors and the
      risk of thrombo-embolic complications. METHOD: We assessed the frequency and the
      risk factors for coil protrusion in 330 unruptured aneurysm embolization cases,
      and examined the occurrence of cerebral infarction by diffusion-weighted magnetic
      resonance imaging (DW-MRI). RESULT: Forty-four instances of coil protrusion were
      encountered during coil embolization (13.3% of cases), but incidence was reduced
      to 33 (10% of cases) by balloon press or insertion of the next coil. Coil
      protrusion occurred more frequently during the last phase of the procedure, and
      both a wide neck (large fundus to neck ratio) (OR = 1.84, P = 0.03) and an
      inadequately stable neck frame (OR = 5.49, P = 0.0007) increased protrusion risk.
      Coil protrusions did not increase the incidence of high-intensity lesions
      (infarcts) on DW-MRI (33.3% vs 29% of cases with no coil protrusion). However,
      longer operation time did increase infarct risk (P = 0.0003). Thus, tail or loop
      type coil protrusion did not increase the risk of thrombo-embolic complications,
      if adequate blood flow was maintained. CONCLUSION: Coil protrusion tended to
      occur more frequently in cases of wide-neck aneurysms with loose neck framing.
      Moderate and less coil protrusion carries no additional thrombo-embolic risk, if
      blood flow is maintained, which can be aided by additional post-operative
      antiplatelet therapy.

PMID- 25964444
TI  - Genetic Distinctiveness of Alexander Archipelago Wolves (Canis lupus ligoni).

PMID- 25964445
TI  - Mexican Wolves Are a Valid Subspecies and an Appropriate Conservation Target.

PMID- 25964446
TI  - Wolf Subspecies: Reply to Weckworth et al. and Fredrickson et al.

PMID- 25964447
TI  - Family functioning, social support, and quality of life for patients with anxiety
      disorder.
AB  - BACKGROUND: Few studies have examined the relationship between family
      functioning, social support and quality of life in patients with anxiety
      disorder. There is a paucity of research on anxiety disorders and their
      predictors in China. AIMS: This study aimed to explore family functioning, social
      support and quality of life for patients with anxiety disorder and examine the
      relationship between these elements. METHODS: A total of 107 patients who met
      Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria
      for anxiety disorder and 80 healthy controls completed the McMaster Family
      Assessment Device, the Perceived Social Support Scale and the short form of the
      Quality of Life Enjoyment and Satisfaction Questionnaire. RESULTS: The findings
      indicate that patients with anxiety disorder in China tend to have poor family
      functioning and quality of life, as well as a higher subjective perception of
      social support. There were strong correlations between family functioning, social
      support and quality of life. Affective involvement and not living with parents
      were identified as risk factors for anxiety disorders, while a high family income
      was a protective factor. CONCLUSION: Anxiety disorder is associated with reduced
      family functioning and poorer quality of life for Chinese patients. In addition,
      the Family Assessment Device is a suitable instrument for evaluating family
      functioning in Chinese patients with anxiety disorder.

PMID- 25964448
TI  - Boredom proneness predicts quality of life in outpatients diagnosed with
      schizophrenia-spectrum disorders.
AB  - BACKGROUND: There is increasing recognition of the clinical significance of
      boredom associated with functional impairments in schizophrenia. Previous work
      has highlighted the importance of motivational deficits more broadly, although no
      study has yet explored the unique effects of boredom on community outcomes. AIMS:
      This study aims to measure boredom proneness among outpatients diagnosed with
      schizophrenia to determine whether it is elevated in this population and to
      determine its relation to quality-of-life outcomes. METHODS: A self-report
      measure of boredom proneness along with standard measures of symptoms and
      functional status was administered to a community-dwelling sample of
      schizophrenia outpatients. RESULTS: Boredom proneness was found to be elevated in
      this population and was associated with reduced quality of life, specifically
      with leisure activity dissatisfaction and reduced sense of financial well-being.
      Negative symptoms were determined to be associated with reduced work and school
      functioning. CONCLUSION: This pattern of unique effects on quality of life
      highlights the clinical relevance of identifying a subjective state of boredom
      and has theoretical importance in distinguishing boredom proneness specifically
      from more general avolitional and amotivational conditions that have tended to be
      the focus of clinical observation and previous research.

PMID- 25964449
TI  - Exercise Interventions in Children and Adolescents With ADHD: A Systematic
      Review.
AB  - OBJECTIVE: Exercise has attracted attention as a potential helpful intervention
      in children with ADHD. Effects are emphasized on cognition, social-emotional, and
      motor development. METHOD: A systematic literature search was conducted using the
      electronic databases Web of Science, PubMed, Scopus, and ERIC to analyze the
      efficacy of different types of exercise interventions in children and adolescents
      with ADHD. Seven studies examining the acute and 14 studies examining the long
      term effects were included. RESULTS: The largest effects were reported for mixed
      exercise programs on ADHD symptomatology and fine motor precision. However,
      because of the large differences in the study designs, the comparability is
      limited. CONCLUSION: At that time, no evidence-based recommendation can be
      formulated regarding frequency, intensity, or duration of exercise. Nevertheless,
      some first trends regarding the effects of certain types of exercise can be
      identified. When focusing on long-term health benefits in children and
      adolescents with ADHD, qualitative exercise characteristics might play an
      important role.

PMID- 25964450
TI  - The impact of maternal infection with Mycobacterium tuberculosis on the infant
      response to bacille Calmette-Guerin immunization.
AB  - Bacille Calmette-Guerin (BCG) immunization provides variable protection against
      tuberculosis. Prenatal antigen exposure may have lifelong effects on responses to
      related antigens and pathogens. We therefore hypothesized that maternal latent
      Mycobacterium tuberculosis infection (LTBI) influences infant responses to BCG
      immunization at birth. We measured antibody (n = 53) and cellular (n = 31)
      responses to M. tuberculosis purified protein derivative (PPD) in infants of
      mothers with and without LTBI, in cord blood and at one and six weeks after BCG.
      The concentrations of PPD-specific antibodies declined between birth (median
      [interquartile range (IQR)]) 5600 ng ml(-1) [3300-11 050] in cord blood) and six
      weeks (0.00 ng ml(-1) [0-288]). Frequencies of PPD-specific IFN-gamma-expressing
      CD4(+)T cells increased at one week and declined between one and six weeks (p =
      0.031). Frequencies of IL-2- and TNF-alpha-expressing PPD-specific CD4(+)T cells
      increased between one and six weeks (p = 0.019, p = 0.009, respectively). At one
      week, the frequency of PPD-specific CD4(+)T cells expressing any of the three
      cytokines, combined, was lower among infants of mothers with LTBI, in crude
      analyses (p = 0.002) and after adjusting for confounders (mean difference, 95% CI
      -0.041% (-0.082, -0.001)). In conclusion, maternal LTBI was associated with lower
      infant anti-mycobacterial T-cell responses immediately following BCG
      immunization. These findings are being explored further in a larger study. 

PMID- 25964451
TI  - Biological challenges to effective vaccines in the developing world.
AB  - The reason for holding a meeting to discuss biological challenges to vaccines is
      simple: not all vaccines work equally well in all settings. This special issue
      reviews the performance of vaccines in challenging environments, summarizes
      current thinking on the reasons why vaccines underperform and considers what
      approaches are necessary to understand the heterogeneity in responses and to
      improve vaccine immunogenicity and efficacy. 

PMID- 25964452
TI  - Is infant immunization by breastfeeding possible?
AB  - Breastfeeding is known as the most efficient way to prevent infectious disease in
      early life. Maternal anti-microbial immunoglobulins transfer through milk confers
      passive immunity to the breastfed child while his immune system is maturing.
      Maternal milk also contains bioactive factors that will stimulate this
      maturation. From the literature on breastfeeding prevention of immune-mediated
      disease and more specifically from our experiments conducted in the field of
      allergic disease prevention, we propose that breastfeeding may also induce
      antigen-specific immune responses in the breastfed child. We found that early
      oral antigen exposure through breast milk leads to tolerance or immune priming
      depending on the nature of the antigen transferred and accompanying maternal milk
      cofactors. Here, we will discuss our data in the light of prevention of
      infectious disease and will propose that possible milk transfer of microbial
      antigen could affect actively the immune response in breastfed children and
      thereby their long-term susceptibility to infectious disease. Further research in
      this direction may lead to novel strategies of early life vaccination, taking
      advantage of the possibility to stimulate antigen-specific immune responses
      through breast milk. 

PMID- 25964453
TI  - Malnutrition and vaccination in developing countries.
AB  - Malnutrition contributes to an estimated 45% of deaths among children under 5
      years of age in developing countries, predominantly due to infections.
      Malnourished children therefore stand to benefit hugely from vaccination, but
      malnutrition has been described as the most common immunodeficiency globally,
      suggesting that they may not be able to respond effectively to vaccines. The
      immunology of malnutrition remains poorly characterized, but is associated with
      impairments in mucosal barrier integrity, and innate and adaptive immune
      dysfunction. Despite this, the majority of malnourished children can mount a
      protective immune response following vaccination, although the timing, quality
      and duration of responses may be impaired. This paper reviews the evidence for
      vaccine immunogenicity in malnourished children, discusses the importance of
      vaccination in prevention of malnutrition and highlights evidence gaps in our
      current knowledge. 

PMID- 25964454
TI  - Genomics of immune response to typhoid and cholera vaccines.
AB  - Considerable variation in antibody response (AR) was observed among recipients of
      an injectable typhoid vaccine and an oral cholera vaccine. We sought to find
      whether polymorphisms in genes of the immune system, both innate and adaptive,
      were associated with the observed variation in response. For both vaccines, we
      were able to discover and validate several polymorphisms that were significantly
      associated with immune response. For the typhoid vaccines, these polymorphisms
      were on genes that belonged to pathways of polysaccharide recognition, signal
      transduction, inhibition of T-cell proliferation, pro-inflammatory signalling and
      eventual production of antimicrobial peptides. For the cholera vaccine, the
      pathways included epithelial barrier integrity, intestinal homeostasis and
      leucocyte recruitment. Even though traditional wisdom indicates that both
      vaccines should act as T-cell-independent antigens, our findings reveal that the
      vaccines induce AR using different pathways. 

PMID- 25964455
TI  - Exploring the role of environmental enteropathy in malnutrition, infant
      development and oral vaccine response.
AB  - Environmental enteropathy (EE) is a poorly defined state of intestinal
      inflammation without overt diarrhoea that occurs in individuals exposed over time
      to poor sanitation and hygiene. It is characterized pathologically by small
      intestine villous blunting and inflammation. In children from low-income
      countries, it is implicated as a cause of malnutrition, oral vaccine failure and
      impaired cognitive development. Here we review the search for non-invasive
      biomarkers to measure EE non-invasively, and assess the current evidence linking
      EE to malnutrition, vaccine failure and neurocognitive development. 

PMID- 25964456
TI  - Probiotics, antibiotics and the immune responses to vaccines.
AB  - Orally delivered vaccines have been shown to perform poorly in developing
      countries. There are marked differences in the structure and the luminal
      environment of the gut in developing countries resulting in changes in immune and
      barrier function. Recent studies using newly developed technology and analytic
      methods have made it increasingly clear that the intestinal microbiota activate a
      multitude of pathways that control innate and adaptive immunity in the gut.
      Several hypotheses have been proposed for the underperformance of oral vaccines
      in developing countries, and modulation of the intestinal microbiota is now being
      tested in human clinical trials. Supplementation with specific strains of
      probiotics has been shown to have modulatory effects on intestinal and systemic
      immune responses in animal models and forms the basis for human studies with
      vaccines. However, most studies published so far that have evaluated the immune
      response to vaccines in children and adults have been small and results have
      varied by age, antigen, type of antibody response and probiotic strain. Use of
      anthelminthic drugs in children has been shown to possibly increase
      immunogenicity following oral cholera vaccination, lending further support to the
      rationale for modulation of the immune response to oral vaccination through the
      intestinal microbiome. 

PMID- 25964457
TI  - Potential for use of retinoic acid as an oral vaccine adjuvant.
AB  - Despite the heavy burden of diarrhoeal disease across much of the tropical world,
      only two diarrhoea-causing pathogens, cholera and rotavirus, are the target of
      commercially available vaccines. Oral vaccines are generally less immunogenic
      than the best parenteral vaccines, but the reasons for this are still debated.
      Over the past decade, several lines of evidence from work in experimental animals
      have suggested that all-trans retinoic acid (ATRA), a form of vitamin A which is
      highly transcriptionally active, can alter the homing receptor expression of T
      lymphocytes. Increased expression of alpha4beta7 integrin and the chemokine
      receptor CCR9 following exposure to ATRA can be used to redirect T cells to the
      gut. Early work in human volunteers suggests that oral ATRA administration 1 h
      prior to dosing with oral typhoid vaccine can augment secretion of specific IgA
      against vaccine-derived lipopolysaccharide into gut secretions. In this review,
      we set out the rationale for using ATRA in this way and assess its likely
      applicability to vaccination programmes for protection of children in low-income
      countries from the considerable mortality caused by diarrhoeal disease.
      Comparison of recent work in experimental animals, non-human primates and men
      suggests that a more detailed understanding of ATRA dosage and kinetics will be
      important to taking forward translational work into human vaccinology. 

PMID- 25964458
TI  - Vaccinology in the era of high-throughput biology.
AB  - Vaccination has been tremendously successful saving lives and preventing
      infections. However, the development of vaccines against global pandemics such as
      HIV, malaria and tuberculosis has been obstructed by several challenges. A major
      challenge is the lack of knowledge about the correlates and mechanisms of
      protective immunity. Recent advances in the application of systems biological
      approaches to analyse immune responses to vaccination in humans are beginning to
      yield new insights about mechanisms of vaccine immunity, and to define molecular
      signatures, induced rapidly after vaccination, that correlate with and predict
      vaccine induced immunity. Here, we review these advances and discuss the
      potential of this systems vaccinology approach in defining novel correlates of
      protection in clinical trials, and in infection-induced 'experimental challenge
      models' in humans. 

PMID- 25964459
TI  - Factors influencing innate immunity and vaccine responses in infancy.
AB  - Despite significant progress in reducing the burden of mortality in children
      under the age of five, reducing mortality in newborns remains a major challenge.
      Infection plays a significant role in infant deaths and interventions such as
      early vaccination or antenatal immunization could make a significant contribution
      to prevention of such deaths. In the last few years, we have gained new insights
      into immune ontogeny and are now beginning to understand the impact of vaccines,
      nutrition and environmental factors on 'training' of the immune response in early
      life. This review article sets out to explain why vaccine responses can be
      heterogeneous between populations and individuals by providing examples chosen to
      illustrate the impact of host, pathogen and environmental factors on shaping the
      immune 'interactome' in young children. 

PMID- 25964460
TI  - Delivering vaccines to the people who need them most.
AB  - Thanks to the Global Alliance for Vaccines and Immunization (GAVI), the Vaccine
      Fund and the Bill & Melinda Gates Foundation, the global health community has
      made enormous progress in providing already existing vaccines to developing
      countries. However, there still exists a gap to develop vaccines for which there
      is no market in the Western world, owing to low economic incentives for the
      private sector to justify the investments necessary for vaccine development. In
      many cases, industry has the technologies, but lacks the impetus to direct
      resources to develop these vaccine products. The present emergency with the Ebola
      vaccine provides us an excellent example where a vaccine was feasible several
      years ago, but the global health community waited for a humanitarian disaster to
      direct efforts and resources to develop this vaccine. In the beginning of 2015,
      the first large-scale trials of two experimental vaccines against Ebola virus
      disease have begun in West Africa. During the past few years, several
      institutions have dedicated efforts to the development of vaccines against
      diseases present only in low-income countries. These include the International
      Vaccine Institute, the Novartis Vaccines Institute for Global Health, the
      Hilleman Institute, the Sabin Vaccine Institute and the Infectious Disease
      Research Institute. Nevertheless, solving this problem requires a more
      significant global effort than that currently invested. These efforts include a
      clear policy, global coordination of funds dedicated to the development of
      neglected disease and an agreement on regulatory strategies and incentives for
      the private sector. 

PMID- 25964461
TI  - Can immunological principles and cross-disciplinary science illuminate the path
      to vaccines for HIV and other global health challenges?
AB  - Vaccines are one of the most impactful and cost-effective public health measures
      of the twentieth century. However, there remain great unmet needs to develop
      vaccines for globally burdensome infectious diseases and to allow more timely
      responses to emerging infectious disease threats. Recent advances in the
      understanding of immunological principles operative not just in model systems but
      in humans in concert with the development and application of powerful new tools
      for profiling human immune responses, in our understanding of pathogen variation
      and evolution, and in the elucidation of the structural aspects of antibody
      pathogen interactions, have illuminated pathways by which these unmet needs might
      be addressed. Using these advances as foundation, we herein present a conceptual
      framework by which the discovery, development and iterative improvement of
      effective vaccines for HIV, malaria and other globally important infectious
      diseases might be accelerated. 

PMID- 25964462
TI  - Systems vaccinology: a promise for the young and the poor.
AB  - As a child, the risk of suffering and dying from infection is higher the younger
      you are; and higher, the less developed a region you are born in. Childhood
      vaccination programmes have greatly reduced mortality around the world, but least
      so for the very young among the very poor of the world. This appears partly owing
      to suboptimal vaccine effectiveness. Unfortunately, although most vaccines are
      administered to the newborn and very young infant (less than or equal to two
      months), we know the least about their host response to vaccination. We thus
      currently lack the knowledge to guide efforts aimed at improving vaccine
      effectiveness in this vulnerable population. Systems vaccinology, the study of
      molecular networks activated by immunization, has begun to provide unprecedented
      insights into mechanisms leading to vaccine-induced protection from infection or
      disease. However, all published reports of systems vaccinology have focused on
      either adults or at most children and older infants, not those most in need, i.e.
      newborns and very young infants. Given that the tools of systems vaccinology work
      perfectly well with very small sample volumes, it is time we deliver the promise
      that systems vaccinology holds for those most in need of vaccine-mediated
      protection from infection. 

PMID- 25964465
TI  - Correction to 'Brown spider monkeys (Ateles hybridus): a model for
      differentiating the role of social networks and physical contact on parasite
      transmission dynamics'.

PMID- 25964463
TI  - Searching for the human genetic factors standing in the way of universally
      effective vaccines.
AB  - Vaccines have revolutionized modern public health. The effectiveness of some
      vaccines is limited by the variation in response observed between individuals and
      across populations. There is compelling evidence that a significant proportion of
      this variability can be attributed to human genetic variation, especially for
      those vaccines administered in early life. Identifying and understanding the
      determinants of this variation could have a far-reaching influence upon future
      methods of vaccine design and deployment. In this review, we summarize the
      genetic studies that have been undertaken attempting to identify the genetic
      determinants of response heterogeneity for the vaccines against hepatitis B,
      measles and rubella. We offer a critical appraisal of these studies and make a
      series of suggestions about how modern genetic techniques, including genome-wide
      association studies, could be used to characterize the genetic architecture of
      vaccine response heterogeneity. We conclude by suggesting how the findings from
      such studies could be translated to improve vaccine effectiveness and target
      vaccination in a more cost-effective manner. 

PMID- 25964464
TI  - Vaccines against enteric infections for the developing world.
AB  - Since the first licensure of the Sabin oral polio vaccine more than 50 years ago,
      only eight enteric vaccines have been licensed for four disease indications, and
      all are given orally. While mucosal vaccines offer programmatically attractive
      tools for facilitating vaccine deployment, their development remains hampered by
      several factors: -limited knowledge regarding the properties of the gut immune
      system during early life; -lack of mucosal adjuvants, limiting mucosal vaccine
      development to live-attenuated or killed whole virus and bacterial vaccines; 
      lack of correlates/surrogates of mucosal immune protection; and -limited
      knowledge of the factors contributing to oral vaccine underperformance in
      children from developing countries. There are now reasons to believe that the
      development of safe and effective mucosal adjuvants and of programmatically sound
      intervention strategies could enhance the efficacy of current and next-generation
      enteric vaccines, especially in lesser developed countries which are often co
      endemic for enteric infections and malnutrition. These vaccines must be safe and
      affordable for the world's poorest, confer long-term protection and herd
      immunity, and must be able to contain epidemics. 

PMID- 25964466
TI  - Chronic neurokinin-1 receptor antagonism fails to ameliorate clinical signs,
      airway hyper-responsiveness or airway eosinophilia in an experimental model of
      feline asthma.
AB  - OBJECTIVES: Feline allergic asthma is a common chronic lower airway disease
      characterized by clinical signs attributed to eosinophilic inflammation, airway
      hyper-responsiveness (AHR) and airway remodeling. Tachykinins released from
      sensory nerves and immune cells bind neurokinin-1 (NK-1) receptors in the lung.
      The resultant neurogenic airway inflammation has been implicated in asthma
      pathogenesis. In mouse models and spontaneous human asthma, NK receptor
      antagonists reduce bronchospasm and inflammation. We hypothesized that chronic
      administration of maropitant, an NK-1 receptor antagonist, would decrease
      clinical signs of asthma, AHR and eosinophilic inflammation in experimentally
      asthmatic cats. METHODS: Cats (n = 6) induced to have asthma using Bermuda grass
      allergen (BGA) were enrolled in a randomized, prospective, placebo-controlled
      crossover design study. Cats received either oral maropitant (2 mg/kg) or placebo
      q48h for 4 weeks; following a 2 week washout, cats were crossed-over to the
      alternate treatment. Study endpoints included subjective clinical scoring systems
      after BGA challenge, ventilator-acquired pulmonary mechanics to assess AHR after
      bronchoprovocation with methacholine, and collection of bronchoalveolar lavage
      fluid to quantify airway eosinophilia. Statistical analysis was performed using a
      Mann-Whitney rank sum test with P <0.05 considered significant. RESULTS:
      Administration of maropitant for 1 month in experimentally asthmatic cats
      produced no significant difference in clinical scoring scheme (P = 0.589 and P =
      1.0), AHR (P = 0.818) or airway eosinophilia (P = 0.669) compared with placebo.
      CONCLUSIONS AND RELEVANCE: Chronic administration of maropitant was ineffective
      at blunting clinical signs, AHR and airway eosinophilia in experimental feline
      asthma and thus cannot be recommended as a novel treatment for this disorder.

PMID- 25964467
TI  - Acute neurokinin-1 receptor antagonism fails to dampen airflow limitation or
      airway eosinophilia in an experimental model of feline asthma.
AB  - OBJECTIVES: Feline allergic asthma is a chronic inflammatory disorder of the
      lower airways that may manifest with acute, life-threatening clinical signs.
      Tachykinins released from sensory nerves and immune cells binding neurokinin (NK)
      1, NK-2 and NK-3 receptors have been implicated in asthma pathogenesis.
      Maropitant, an NK-1 receptor antagonist, blocks neuroimmune pathways and may be a
      viable treatment option for cats in asthmatic crisis. Using an experimental
      chronic allergic feline asthma model, we hypothesized that a single dose of
      maropitant given immediately after allergen challenge would blunt clinical signs,
      airway hyperresponsiveness (AHR) and airway eosinophilia. METHODS: Cats (n = 7)
      induced to have an asthmatic phenotype using Bermuda grass allergen (BGA) were
      enrolled in a prospective, placebo-controlled crossover design study. Cats
      randomly received maropitant (2 mg/kg SC) or placebo (saline SC) immediately post
      BGA challenge, followed 12 h later by pulmonary mechanics testing and measurement
      of airway eosinophils. After a 2 week washout, cats were crossed-over to the
      alternate treatment. Study endpoints included subjective clinical scoring systems
      post-BGA challenge, ventilator-acquired pulmonary mechanics to assess AHR after
      bronchoprovocation with methacholine and collection of bronchoalveolar lavage
      fluid to quantify airway eosinophilia. Data were analyzed using a Mann-Whitney
      rank sum test with P <0.05 considered significant. RESULTS: A single injection of
      maropitant failed to diminish clinical composite score (P = 0.902), visual
      analogue scale scoring (P = 0.710), AHR (P = 0.456) or airway eosinophilia (P =
      0.165) compared with placebo. CONCLUSIONS AND RELEVANCE: A single injection of
      maropitant given immediately post-allergen challenge was ineffective at blunting
      clinical signs, AHR and airway eosinophilia, and cannot be recommended as
      treatment for feline status asthmaticus.

PMID- 25964468
TI  - Human Milk for Sale: Buyer Beware!

PMID- 25964469
TI  - Generation of a Novel Staphylococcus aureus Ghost Vaccine and Examination of Its
      Immunogenicity against Virulent Challenge in Rats.
AB  - Staphylococcus aureus is a Gram-positive pathogen that causes a wide range of
      infections in humans and animals. Bacterial ghosts are nonliving, empty cell
      envelopes and are well represented as novel vaccine candidates. In this study, we
      examined the immunogenicity and protective efficacy of S. aureus ghosts (SAGs)
      against a virulent challenge in rats. Nonliving SAGs were generated by using the
      MIC of sodium hydroxide. The formation of a transmembrane lysis tunnel structure
      in SAGs was visualized by scanning electron microscopy. To investigate these SAGs
      as a vaccine candidate, rats were divided into four groups, A (nonimmunized
      control), B (orally immunized), C (subcutaneously immunized), and D
      (intravenously immunized). The IgG antibody responses were significantly stronger
      in the SAG-immunized groups than in the nonimmunized control group (P < 0.05).
      Moreover, a significant increase in the populations of CD4(+) and CD8(+) T cells
      was observed in all three immunized groups (P < 0.05). We also found that serum
      bactericidal antibodies were significantly elicited in the SAG-immunized groups
      (P < 0.05). Most importantly, the bacterial loads in the immunized groups were
      significantly lower than those in the nonimmunized control group (P < 0.01).
      These results suggest that immunization with SAGs induces immune responses and
      provides protection against a virulent S. aureus challenge. 

PMID- 25964470
TI  - Interaction of Salmonella enterica Serovar Typhimurium with Intestinal Organoids
      Derived from Human Induced Pluripotent Stem Cells.
AB  - The intestinal mucosa forms the first line of defense against infections mediated
      by enteric pathogens such as salmonellae. Here we exploited intestinal
      "organoids" (iHOs) generated from human induced pluripotent stem cells (hIPSCs)
      to explore the interaction of Salmonella enterica serovar Typhimurium with iHOs.
      Imaging and RNA sequencing were used to analyze these interactions, and clear
      changes in transcriptional signatures were detected, including altered patterns
      of cytokine expression after the exposure of iHOs to bacteria. S. Typhimurium
      microinjected into the lumen of iHOs was able to invade the epithelial barrier,
      with many bacteria residing within Salmonella-containing vacuoles. An S.
      Typhimurium invA mutant defective in the Salmonella pathogenicity island 1
      invasion apparatus was less capable of invading the iHO epithelium. Hence, we
      provide evidence that hIPSC-derived organoids are a promising model of the
      intestinal epithelium for assessing interactions with enteric pathogens. 

PMID- 25964472
TI  - Role of Phenol-Soluble Modulins in Formation of Staphylococcus aureus Biofilms in
      Synovial Fluid.
AB  - Staphylococcus aureus is a leading cause of prosthetic joint infections, which,
      as we recently showed, proceed with the involvement of biofilm-like clusters that
      cause recalcitrance to antibiotic treatment. Here we analyzed why these clusters
      grow extraordinarily large, reaching macroscopically visible extensions (>1 mm).
      We found that while specific S. aureus surface proteins are a prerequisite for
      agglomeration in synovial fluid, low activity of the Agr regulatory system and
      subsequent low production of the phenol-soluble modulin (PSM) surfactant peptides
      cause agglomerates to grow to exceptional dimensions. Our results indicate that
      PSMs function by disrupting interactions of biofilm matrix molecules, such as the
      polysaccharide intercellular adhesin (PIA), with the bacterial cell surface.
      Together, our findings support a two-step model of staphylococcal prosthetic
      joint infection: As we previously reported, interaction of S. aureus surface
      proteins with host matrix proteins such as fibrin initiates agglomeration; our
      present results show that, thereafter, the bacterial agglomerates grow to
      extremely large sizes owing to the lack of PSM expression under the specific
      conditions present in joints. Our findings provide a mechanistic explanation for
      the reported extreme resistance of joint infection to antibiotic treatment, lend
      support to the notions that Agr functionality and PSM production play a major
      role in defining different forms of S. aureus infection, and have important
      implications for antistaphylococcal therapeutic strategies. 

PMID- 25964471
TI  - Comparative Roles of the Two Helicobacter pylori Thioredoxins in Preventing
      Macromolecule Damage.
AB  - Thioredoxins are highly conserved throughout a wide range of organisms, and they
      are essential for the isurvival of oxygen-sensitive cells. The gastric pathogen
      Helicobacter pylori uses the thioredoxin system to maintain its thiol/disulfide
      balance. There are two thioredoxins present in H. pylori, Trx1 and Trx2 (herein
      referred to as TrxA and TrxC). TrxA has been shown to be important as an electron
      donor for some antioxidant enzymes, but the function of TrxC remains unknown (L.
      M. Baker, A. Raudonikiene, P. S. Hoffman, and L. B. Poole, J Bacteriol 183:1961
      1973, 2001; P. Alamuri and R. J. Maier, J Bacteriol 188:5839-5850, 2006). We
      demonstrate that both TrxA and TrxC are important in protecting H. pylori from
      oxidative stress. Individual DeltatrxA and DeltatrxC deletion mutant strains each
      show a greater abundance of lipid peroxides and suffer more DNA damage and more
      protein carbonylation than the parent. Both deletion mutants were much more
      sensitive to O2-mediated viability loss than the parent. Unexpectedly, the
      oxidative DNA damage and protein carbonylation was more severe in the DeltatrxC
      mutant than in the DeltatrxA mutant; it had 20-fold- and 4-fold-more carbonylated
      protein content than the wild type and the DeltatrxA strain, respectively, after
      4 h of atmospheric O2 stress. trx transcript abundance was altered by the
      deletion of the heterologous trx gene. The DeltatrxC mutant lacked mouse
      colonization ability, while the ability to colonize mouse stomachs was
      significantly reduced in the DeltatrxA mutant. 

PMID- 25964474
TI  - Allergic Lung Inflammation Reduces Tissue Invasion and Enhances Survival from
      Pulmonary Pneumococcal Infection in Mice, Which Correlates with Increased
      Expression of Transforming Growth Factor beta1 and SiglecF(low) Alveolar
      Macrophages.
AB  - Asthma is generally thought to confer an increased risk for invasive pneumococcal
      disease (IPD) in humans. However, recent reports suggest that mortality rates
      from IPD are unaffected in patients with asthma and that chronic obstructive
      pulmonary disease (COPD), a condition similar to asthma, protects against the
      development of complicated pneumonia. To clarify the effects of asthma on the
      subsequent susceptibility to pneumococcal infection, ovalbumin (OVA)-induced
      allergic lung inflammation (ALI) was induced in mice followed by intranasal
      infection with A66.1 serotype 3 Streptococcus pneumoniae. Surprisingly, mice with
      ALI were significantly more resistant to lethal infection than non-ALI mice. The
      heightened resistance observed following ALI correlated with enhanced early
      clearance of pneumococci from the lung, decreased bacterial invasion from the
      airway into the lung tissue, a blunted inflammatory cytokine and neutrophil
      response to infection, and enhanced expression of transforming growth factor
      beta1 (TGF-beta1). Neutrophil depletion prior to infection had no effect on
      enhanced early bacterial clearance or resistance to IPD in mice with ALI.
      Although eosinophils recruited into the lung during ALI appeared to be capable of
      phagocytizing bacteria, neutralization of interleukin-5 (IL-5) to inhibit
      eosinophil recruitment likewise had no effect on early clearance or survival
      following infection. However, enhanced resistance was associated with an increase
      in levels of clodronate-sensitive, phagocytic SiglecF(low) alveolar macrophages
      within the airways following ALI. These findings suggest that, while the risk of
      developing IPD may actually be decreased in patients with acute asthma,
      additional clinical data are needed to better understand the risk of IPD in
      patients with different asthma phenotypes. 

PMID- 25964473
TI  - The Human Antimicrobial Protein Calgranulin C Participates in Control of
      Helicobacter pylori Growth and Regulation of Virulence.
AB  - During infectious processes, antimicrobial proteins are produced by both
      epithelial cells and innate immune cells. Some of these antimicrobial molecules
      function by targeting transition metals and sequestering these metals in a
      process referred to as "nutritional immunity." This chelation strategy ultimately
      starves invading pathogens, limiting their growth within the vertebrate host.
      Recent evidence suggests that these metal-binding antimicrobial molecules have
      the capacity to affect bacterial virulence, including toxin secretion systems.
      Our previous work showed that the S100A8/S100A9 heterodimer (calprotectin, or
      calgranulin A/B) binds zinc and represses the elaboration of the H. pylori cag
      type IV secretion system (T4SS). However, there are several other S100 proteins
      that are produced in response to infection. We hypothesized that the zinc-binding
      protein S100A12 (calgranulin C) is induced in response to H. pylori infection and
      also plays a role in controlling H. pylori growth and virulence. To test this, we
      analyzed gastric biopsy specimens from H. pylori-positive and -negative patients
      for S100A12 expression. These assays showed that S100A12 is induced in response
      to H. pylori infection and inhibits bacterial growth and viability in vitro by
      binding nutrient zinc. Furthermore, the data establish that the zinc-binding
      activity of the S100A12 protein represses the activity of the cag T4SS, as
      evidenced by the gastric cell "hummingbird" phenotype, interleukin 8 (IL-8)
      secretion, and CagA translocation assays. In addition, high-resolution field
      emission gun scanning electron microscopy (FEG-SEM) was used to demonstrate that
      S100A12 represses biogenesis of the cag T4SS. Together with our previous work,
      these data reveal that multiple S100 proteins can repress the elaboration of an
      oncogenic bacterial surface organelle. 

PMID- 25964475
TI  - Vitamin A-Deficient Hosts Become Nonsymptomatic Reservoirs of Escherichia coli
      Like Enteric Infections.
AB  - Vitamin A deficiency (A(-)) remains a public health concern in developing
      countries and is associated with increased susceptibility to infection.
      Citrobacter rodentium was used to model human Escherichia coli infections. A(-)
      mice developed a severe and lethal (40%) infection. Vitamin A-sufficient (A(+))
      mice survived and cleared the infection by day 25. Retinoic acid treatment of A(
      ) mice at the peak of the infection eliminated C. rodentium within 16 days.
      Inflammation levels were not different between A(+) and A(-) mouse colons,
      although the A(-) mice were still infected at day 37. Increased mortality of A(-)
      mice was not due to systemic cytokine production, an inability to clear systemic
      C. rodentium, or increased pathogenicity. Instead, A(-) mice developed a severe
      gut infection with most of the A(-) mice surviving and resolving inflammation but
      not eliminating the infection. Improvements in vitamin A status might decrease
      susceptibility to enteric pathogens and prevent potential carriers from spreading
      infection to susceptible populations. 

PMID- 25964476
TI  - Identification of OprF as a complement component C3 binding acceptor molecule on
      the surface of Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is a versatile opportunistic pathogen that can cause
      devastating persistent infections. Complement is a highly conserved pathway of
      the innate immune system, and its role in the first line of defense against
      pathogens is widely appreciated. One of the earliest events in the complement
      cascade is the conversion of C3 to C3a and C3b, the latter typically binds to one
      or more acceptor molecules on the pathogen surface. We previously demonstrated
      that complement C3b binding acceptors exist on the P. aeruginosa surface. In the
      current study, we utilized either C3 polyclonal or C3b monoclonal antibodies in a
      far-Western technique followed by mass spectroscopy to identify the C3b acceptor
      molecule(s) on the P. aeruginosa surface. Our data provide evidence that OprF (an
      outer membrane porin, highly conserved in the Pseudomonadaceae) binds C3b. An
      oprF-deficient P. aeruginosa strain exhibits reduced C3 deposition compared to
      the wild type. We observed reduced internalization of oprF-deficient bacteria by
      neutrophils after opsonization compared with wild-type P. aeruginosa.
      Heterologous expression of OprF significantly enhanced C3b binding and increased
      serum-mediated bactericidal effects in complement-susceptible Escherichia coli.
      Furthermore, the predicted secondary structure of the C-terminal, surface-exposed
      region of OprF has high structural identity to the OmpA domain of several other
      Gram-negative bacteria, one of which is known to bind C3b. Therefore, these
      findings provide new insights into the biology of complement interactions with P.
      aeruginosa and other Gram-negative bacteria. 

PMID- 25964477
TI  - Toll-Like Receptor 9-Mediated Inflammation Triggers Alveolar Bone Loss in
      Experimental Murine Periodontitis.
AB  - Chronic periodontitis is a local inflammatory disease induced by a dysbiotic
      microbiota and leading to destruction of the tooth-supporting structures.
      Microbial nucleic acids are abundantly present in the periodontium, derived
      through release after phagocytic uptake of microbes and/or from biofilm
      associated extracellular DNA. Binding of microbial DNA to its cognate receptors,
      such as Toll-like receptor 9 (TLR9), can trigger inflammation. In this study, we
      utilized TLR9 knockout (TLR9(-/-)) mice and wild-type (WT) controls in a murine
      model of Porphyromonas gingivalis-induced periodontitis and report the first in
      vivo evidence that TLR9 signaling mediates the induction of periodontal bone
      loss. P. gingivalis-infected WT mice exhibited significantly increased bone loss
      compared to that in sham-infected WT mice or P. gingivalis-infected TLR9(-/-)
      mice, which were resistant to bone loss. Consistent with this, the expression
      levels of interleukin 6 (IL-6), tumor necrosis factor (TNF), and receptor
      activator of nuclear factor kappa B ligand (RANKL) were significantly elevated in
      the gingival tissues of the infected WT mice but not in infected TLR9(-/-) mice
      compared to their levels in controls. Ex vivo studies using splenocytes and bone
      marrow-derived macrophages revealed significantly diminished cytokine production
      in TLR9(-/-) cells relative to the cytokine production in WT cells in response to
      P. gingivalis, thereby implicating TLR9 in inflammatory responses to this
      organism. Intriguingly, compared to the cytokine production in WT cells, TLR9(-/
      ) cells exhibited significantly decreased proinflammatory cytokine production
      upon challenge with lipopolysaccharide (LPS) (TLR4 agonist) or Pam3Cys (TLR2
      agonist), suggesting possible cross talk between TLR9, TLR4, and TLR2.
      Collectively, our results provide the first proof-of-concept evidence implicating
      TLR9-triggered inflammation in periodontal disease pathogenesis, thereby
      identifying a new potential therapeutic target to control periodontal
      inflammation. 

PMID- 25964478
TI  - Lumbar puncture refusal in sub-Saharan Africa: A call for further understanding
      and intervention.

PMID- 25964479
TI  - Neuropsychiatric phenomena in the medieval text Cantigas de Santa Maria.
AB  - OBJECTIVE: To discuss the neuropsychiatric phenomena described in Cantigas de
      Santa Maria (Canticles of St. Mary [CSM]). BACKGROUND: CSM is a collection of 427
      canticles composed in Galician-Portuguese between 1252 and 1284 at the Court of
      King Alfonso X the Wise of Spain (1221-1284). The canticles (of which 9 are
      repeated) include devotional and liturgical poems and 353 narrative stories
      consisting mainly of depictions of Marian miracles. Most are set to music and
      many are illustrated. METHODS: We reviewed the canticles for description of
      miracles and other neuropsychiatric phenomena. Two neurologists reached a
      consensus about the descriptions. RESULTS: Of the 353 miracles, 279 medically
      relevant facts (from 187 canticles) and 25 instances of resurrection were
      reported. Possible neuropsychiatric conditions were described in 98 canticles.
      Physicians were mentioned in 16 narratives. The most common neurologic conditions
      detailed were blindness (n = 17), dystonia, weakness, and deformities (n = 20).
      Other common conditions included psychosis (n = 15), speech disorder/deaf-mutism
      (n = 12), infections (n = 15), sexual dysfunction/infertility/obstetrical
      gynecologic issues (n = 18), head trauma (n = 5), ergotism/St. Anthony's fire (n
      = 7), and others. There were 9 instances of prodromic mystical
      experiences/hallucinations heralding death. CONCLUSIONS: While limited by
      retrospection and interpretation of neuropsychiatric phenomena in the medieval
      context, these short accounts are among the first descriptions of
      neuropsychiatric conditions in early Portuguese/Galician. They reflect how
      medieval societies used rational and irrational approaches to understand
      occurrences in their lives.

PMID- 25964480
TI  - Vascular-induced compensatory pseudo-retrocollis.

PMID- 25964481
TI  - Combined analysis of TERT, EGFR, and IDH status defines distinct prognostic
      glioblastoma classes.

PMID- 25964482
TI  - Neurology mission(s) impossible.

PMID- 25964483
TI  - Clinical Reasoning: A patient with rapidly progressive sensory loss and
      imbalance.

PMID- 25964484
TI  - Clinical Reasoning: Burning hands and feet.

PMID- 25964485
TI  - Teaching NeuroImages: Upright-supine test to evaluate vertical diplopia.

PMID- 25964486
TI  - CXCL14 displays antimicrobial activity against respiratory tract bacteria and
      contributes to clearance of Streptococcus pneumoniae pulmonary infection.
AB  - CXCL14 is a chemokine with an atypical, yet highly conserved, primary structure
      characterized by a short N terminus and high sequence identity between human and
      mouse. Although it induces chemotaxis of monocytic cells at high concentrations,
      its physiological role in leukocyte trafficking remains elusive. In contrast,
      several studies have demonstrated that CXCL14 is a broad-spectrum antimicrobial
      peptide that is expressed abundantly and constitutively in epithelial tissues. In
      this study, we further explored the antimicrobial properties of CXCL14 against
      respiratory pathogens in vitro and in vivo. We found that CXCL14 potently killed
      Pseudomonas aeruginosa, Streptococcus mitis, and Streptococcus pneumoniae in a
      dose-dependent manner in part through membrane depolarization and rupture. By
      performing structure-activity studies, we found that the activity against Gram
      negative bacteria was largely associated with the N-terminal peptide CXCL141-13.
      Interestingly, the central part of the molecule representing the beta-sheet also
      maintained ~62% killing activity and was sufficient to induce chemotaxis of THP-1
      cells. The C-terminal alpha-helix of CXCL14 had neither antimicrobial nor
      chemotactic effect. To investigate a physiological function for CXCL14 in innate
      immunity in vivo, we infected CXCL14-deficient mice with lung pathogens and we
      found that CXCL14 contributed to enhanced clearance of Streptococcus pneumoniae,
      but not Pseudomonas aeruginosa. Our comprehensive studies reflect the complex
      bactericidal mechanisms of CXCL14, and we propose that different structural
      features are relevant for the killing of Gram-negative and Gram-positive
      bacteria. Taken together, our studies show that evolutionary-conserved features
      of CXCL14 are important for constitutive antimicrobial defenses against
      pneumonia.

PMID- 25964487
TI  - Pyruvate dehydrogenase kinase 1 participates in macrophage polarization via
      regulating glucose metabolism.
AB  - The M1 and M2 polarized phenotypes dictate distinctive roles for macrophages as
      they participate in inflammatory disorders. There has been growing interest in
      the role of cellular metabolism in macrophage polarization. However, it is
      currently unclear whether different aspects of a specific metabolic program
      coordinately regulate this cellular process. In this study, we found that
      pyruvate dehydrogenase kinase 1 (PDK1), a key regulatory enzyme in glucose
      metabolism, plays an important role in the differential activation of
      macrophages. Knockdown of PDK1 diminished M1, whereas it enhanced M2 activation
      of macrophages. Mechanistically, PDK1 knockdown led to diminished aerobic
      glycolysis in M1 macrophages, which likely accounts for the attenuated
      inflammatory response in these cells. Furthermore, we found that mitochondrial
      respiration is enhanced during and required by the early activation of M2
      macrophages. Suppression of glucose oxidation, but not that of fatty acids,
      inhibits this process. Consistent with its inhibitory role in early M2
      activation, knockdown of PDK1 enhanced mitochondrial respiration in macrophages.
      Our data suggest that two arms of the glucose metabolism synergistically regulate
      the differential activation of macrophages. Our findings also highlight the
      central role of PDK1 in this event via controlling glycolysis and glucose
      oxidation.

PMID- 25964489
TI  - Candida albicans stimulates IL-23 release by human dendritic cells and downstream
      IL-17 secretion by Vdelta1 T cells.
AB  - gammadelta T cells expressing the Vdelta1 TCR are expanded in patients with HIV
      infection. We show in this article that circulating Vdelta1 T cell numbers are
      particularly high in patients with HIV and candidiasis, and that these cells
      expand and produce IL-17 in response to Candida albicans in vitro. Although C.
      albicans could directly stimulate IL-17 production by a subset of Vdelta1 T
      cells, fungus-treated dendritic cells (DCs) were required to expand C. albicans
      responsive Vdelta1 T cells to generate sufficient numbers of cells to release IL
      17 at levels detectable by ELISA. C. albicans induced the release of IL-1beta, IL
      6, and IL-23 by DCs, but addition of these cytokines or supernatants of C.
      albicans-treated DCs to Vdelta1 T cells was not sufficient to induce
      proliferation. We found that direct contact with DCs was required for Vdelta1 T
      cell proliferation, whereas IL-23R-blocking studies showed that IL-23 was
      required for optimal C. albicans-induced IL-17 production. Because IL-17 affords
      protection against both HIV and C. albicans, and because Vdelta1 T cells are not
      depleted by HIV, these cells are likely to be an important source of IL-17 in HIV
      infected patients with candidiasis, in whom CD4(+) Th17 responses are impaired.
      These data show that C. albicans stimulates proliferation and IL-17 production by
      Vdelta1 T cells by a mechanism that involves IL-23 release by DCs. 

PMID- 25964488
TI  - GIMAP GTPase family genes: potential modifiers in autoimmune diabetes, asthma,
      and allergy.
AB  - GTPase of the immunity-associated protein (GIMAP) family members are
      differentially regulated during human Th cell differentiation and have been
      previously connected to immune-mediated disorders in animal studies. GIMAP4 is
      believed to contribute to the Th cell subtype-driven immunological balance via
      its role in T cell survival. GIMAP5 has a key role in BB-DR rat and NOD mouse
      lymphopenia. To elucidate GIMAP4 and GIMAP5 function and role in human immunity,
      we conducted a study combining genetic association in different immunological
      diseases and complementing functional analyses. Single nucleotide polymorphisms
      tagging the GIMAP haplotype variation were genotyped in Finnish type 1 diabetes
      (T1D) families and in a prospective Swedish asthma and allergic sensitization
      birth cohort. Initially, GIMAP5 rs6965571 was associated with risk for asthma and
      allergic sensitization (odds ratio [OR] 3.74, p = 0.00072, and OR 2.70, p =
      0.0063, respectively) and protection from T1D (OR 0.64, p = 0.0058); GIMAP4
      rs13222905 was associated with asthma (OR 1.28, p = 0.035) and allergic
      sensitization (OR 1.27, p = 0.0068). However, after false discovery rate
      correction for multiple testing, only the associations of GIMAP4 with allergic
      sensitization and GIMAP5 with asthma remained significant. In addition,
      transcription factor binding sites surrounding the associated loci were
      predicted. A gene-gene interaction in the T1D data were observed between the
      IL2RA rs2104286 and GIMAP4 rs9640279 (OR 1.52, p = 0.0064) and indicated between
      INS rs689 and GIMAP5 rs2286899. The follow-up functional analyses revealed lower
      IL-2RA expression upon GIMAP4 knockdown and an effect of GIMAP5 rs2286899
      genotype on protein expression. Thus, the potential role of GIMAP4 and GIMAP5 as
      modifiers of immune-mediated diseases cannot be discarded.

PMID- 25964490
TI  - IRF-1 promotes liver transplant ischemia/reperfusion injury via hepatocyte IL
      15/IL-15Ralpha production.
AB  - Ischemia and reperfusion (I/R) injury following liver transplantation (LTx) is an
      important problem that significantly impacts clinical outcomes. IFN regulatory
      factor-1 (IRF-1) is a nuclear transcription factor that plays a critical role in
      liver injury. Our objective was to determine the immunomodulatory role of IRF-1
      during I/R injury following allogeneic LTx. IRF-1 was induced in liver grafts
      immediately after reperfusion in both human and mouse LTx. IRF-1 contributed
      significantly to I/R injury because IRF-1-knockout (KO) grafts displayed much
      less damage as assessed by serum alanine aminotransferase and histology. In
      vitro, IRF-1 regulated both constitutive and induced expression of IL-15, as well
      as IL-15Ralpha mRNA expression in murine hepatocytes and liver dendritic cells.
      Specific knockdown of IRF-1 in human primary hepatocytes gave similar results. In
      addition, we identified hepatocytes as the major producer of soluble IL-15/IL
      15Ralpha complexes in the liver. IRF-1-KO livers had significantly reduced NK,
      NKT, and CD8(+) T cell numbers, whereas rIL-15/IL-15Ralpha restored these immune
      cells, augmented cytotoxic effector molecules, promoted systemic inflammatory
      responses, and exacerbated liver injury in IRF-1-KO graft recipients. These
      results indicate that IRF-1 promotes LTx I/R injury via hepatocyte IL-15/IL
      15Ralpha production and suggest that targeting IRF-1 and IL-15/IL-15Ralpha may be
      effective in reducing I/R injury associated with LTx.

PMID- 25964492
TI  - Identification of the inflammasome Nlrp1b as the candidate gene conferring
      diabetes risk at the Idd4.1 locus in the nonobese diabetic mouse.
AB  - Type 1 diabetes in the NOD mouse model has been linked to >30 insulin-dependent
      diabetes (Idd) susceptibility loci. Idd4 on chromosome 11 consists of two
      subloci, Idd4.1 and Idd4.2. Using congenic analysis of alleles in NOD and NOD
      resistant (NOR) mice, we previously defined Idd4.1 as an interval containing >50
      genes that controlled expression of genes in the type 1 IFN pathway. In this
      study, we report refined mapping of Idd4.1 to a 1.1-Mb chromosomal region and
      provide genomic sequence analysis and mechanistic evidence supporting its role in
      innate immune regulation of islet-directed autoimmunity. Genetic variation at
      Idd4.1 was mediated by radiation-sensitive hematopoietic cells, and type 1
      diabetes protection conferred by the NOR allele was abrogated in mice treated
      with exogenous type 1 IFN-beta. Next generation sequence analysis of the full
      Idd4.1 genomic interval in NOD and NOR strains supported Nlrp1b as a strong
      candidate gene for Idd4.1. Nlrp1b belongs to the Nod-like receptor (NLR) gene
      family and contributes to inflammasome assembly, caspase-1 recruitment, and
      release of IL-1beta. The Nlrp1b of NOR was expressed as an alternative spliced
      isoform that skips exon 9, resulting in a premature stop codon predicted to
      encode a truncated protein. Functional analysis of the truncated NOR Nlrp1b
      protein demonstrated that it was unable to recruit caspase-1 and process IL
      1beta. Our data suggest that Idd4.1-dependent protection from islet autoimmunity
      is mediated by differences in type 1 IFN- and IL-1beta-dependent immune responses
      resulting from genetic variation in Nlrp1b.

PMID- 25964491
TI  - Diverse antibody genetic and recognition properties revealed following HIV-1
      envelope glycoprotein immunization.
AB  - Isolation of mAbs elicited by vaccination provides opportunities to define the
      development of effective immunity. Ab responses elicited by current HIV-1
      envelope glycoprotein (Env) immunogens display narrow neutralizing activity with
      limited capacity to block infection by tier 2 viruses. Intense work in the field
      suggests that improved Env immunogens are forthcoming, and it is therefore
      important to concurrently develop approaches to investigate the quality of
      vaccine-elicited responses at a higher level of resolution. In this study, we
      cloned a representative set of mAbs elicited by a model Env immunogen in rhesus
      macaques and comprehensively characterized their genetic and functional
      properties. The mAbs were genetically diverse, even within groups of Abs
      targeting the same subregion of Env, consistent with a highly polyclonal
      response. mAbs directed against two subdeterminants of Env, the CD4 binding site
      and V region 3, could in part account for the neutralizing activity observed in
      the plasma of the animal from which they were cloned, demonstrating the power of
      mAb isolation for a detailed understanding of the elicited response. Finally,
      through comparative analyses of mAb binding and neutralizing capacity of HIV-1
      using matched Envs, we demonstrate complex relationships between epitope
      recognition and accessibility, highlighting the protective quaternary packing of
      the HIV-1 spike relative to vaccine-induced mAbs.

PMID- 25964493
TI  - Immune tolerance induction with multiepitope peptide derived from citrullinated
      autoantigens attenuates arthritis manifestations in adjuvant arthritis rats.
AB  - Citrullinated peptides are major targets of disease-specific autoantibodies in
      rheumatoid arthritis. Currently, citrullinated peptides are used as biomarkers
      for diagnosing rheumatoid arthritis by measuring anti-citrullinated protein Ab
      (ACPA) titers in patients' sera. The accumulation of citrullinated proteins at
      synovial inflammation sites suggests that they are possible targets for tolerance
      induction. The objective of the present study was to determine whether
      citrullinated peptides could induce tolerance in an experimental arthritis model
      in rats. In view of the multiplicity of target citrullinated autoantigens
      described for ACPA, we generated a multiepitope citrullinated peptide (Cit-ME),
      derived from major prevalent citrullinated autoantigens (citrullinated filaggrin,
      fibrinogen, vimentin, and collagen type II), and studied its effects on arthritic
      rats. Adjuvant-induced arthritis was induced in Lewis rats. Beginning at day 7
      after disease induction, the rats received eight s.c. injections of Cit-ME on
      alternate days. Differences in clinical status and modulation of T cell
      populations were analyzed. In adjuvant-induced arthritis rats treated with Cit
      ME, disease severity was significantly reduced compared with that of untreated
      rats. Moreover, amelioration of disease manifestations was related to an
      increased regulatory T cell subset and an elevated apoptosis rate of T cells
      associated with reduced Th17 cells. Thus, the use of citrullinated peptides-based
      immunotherapy may be a promising approach for tolerance induction in experimental
      arthritis and perhaps even in susceptible individuals that are ACPA-seropositive
      in human arthritis.

PMID- 25964494
TI  - Glucocorticoid-induced leucine zipper: a critical factor in macrophage endotoxin
      tolerance.
AB  - Induction of glucocorticoid-induced leucine zipper (GILZ) by glucocorticoids
      plays a key role in their anti-inflammatory action. In activated macrophages,
      GILZ levels are downregulated via tristetraprolin-mediated GILZ mRNA
      destabilization. To assess the functional significance of GILZ downregulation, we
      generated myeloid-specific GILZ knockout (KO) mice. GILZ-deficient macrophages
      displayed a higher responsiveness toward LPS, as indicated by increased TNF-alpha
      and IL-1beta expression. This effect was due to an activation of ERK, which was
      significantly amplified in GILZ KO cells. The LPS-induced activation of
      macrophages is attenuated upon pretreatment of macrophages with low-dose LPS, an
      effect termed endotoxin tolerance. In LPS-tolerant macrophages, GILZ mRNA was
      stabilized, whereas ERK activation was strongly decreased. In contrast, GILZ KO
      macrophages exhibited a strongly reduced desensitization. To explore the
      contribution of GILZ expression in macrophages to endotoxin tolerance in vivo, we
      treated GILZ KO mice with repeated i.p. injections of low-dose LPS followed by
      treatment with high-dose LPS. LPS pretreatment resulted in reduced
      proinflammatory mediator expression upon high-dose LPS treatment in serum and
      tissues. In contrast, cytokine induction was preserved in tolerized GILZ KO
      animals. In summary, our data suggest that GILZ is a key regulator of macrophage
      functions.

PMID- 25964495
TI  - Cutting edge: Bcl6-interacting corepressor contributes to germinal center T
      follicular helper cell formation and B cell helper function.
AB  - CD4(+) germinal center (GC)-T follicular helper (Tfh) cells help B cells become
      long-lived plasma cells and memory cells. The transcriptional repressor Bcl6
      plays a key role in GC-Tfh formation by inhibiting the expression of genes that
      promote differentiation into other lineages. We determined whether BCOR, a
      component of a Polycomb repressive complex that interacts with the Bcl6 BTB
      domain, influences GC-Tfh differentiation. T cell-targeted BCOR deficiency led to
      a substantial loss of peptide:MHC class II-specific GC-Tfh cells following
      Listeria monocytogenes infection and a 2-fold decrease following immunization
      with a peptide in CFA. The reduction in GC-Tfh cells was associated with
      diminished plasma cell and GC B cell formation. Thus, T cell-expressed BCOR is
      critical for optimal GC-Tfh cell differentiation and humoral immunity.

PMID- 25964496
TI  - When Optimal Strategy Matters to Prey Fish.
AB  - Predator-prey interactions are commonly studied with an interest in determining
      the optimal strategy for prey. However, the implications of deviating from
      optimal strategy are often unclear. The present study considered these
      consequences by studying how the direction of an escape response affects the
      strategy of prey fish. We simulated these interactions with numerical and
      analytical mathematics and compared our predictions with measurements in
      zebrafish larvae (Danio rerio), which are preyed upon by adults of the same
      species. Consistent with existing theory, we treated the minimum distance between
      predator and prey as the strategic payoff that prey aim to maximize. We found
      that these interactions may be characterized by three strategic domains that are
      defined by the speed of predator relative to the prey. The "fast predator" domain
      occurs when the predator is more than an order of magnitude faster than the prey.
      The escape direction of the prey had only a small effect on the minimum distance
      under these conditions. For the "slow predator" domain, when the prey is faster
      than the predator, we found that differences in direction had no effect on the
      minimum distance for a broad range of escape angles. This was the regime in which
      zebrafish were found to operate. In contrast, the optimal escape angle offers a
      large benefit to the minimum distance in the intermediate strategic domain.
      Therefore, optimal strategy is most meaningful to prey fish when predators are
      faster than prey by less than a factor of 10. This demonstrates that the strategy
      of a prey animal does not matter under certain conditions that are created by the
      behavior of the predator. 

PMID- 25964497
TI  - Potential Mechanisms Driving Population Variation in Spatial Memory and the
      Hippocampus in Food-caching Chickadees.
AB  - Harsh environments and severe winters have been hypothesized to favor improvement
      of the cognitive abilities necessary for successful foraging. Geographic
      variation in winter climate, then, is likely associated with differences in
      selection pressures on cognitive ability, which could lead to evolutionary
      changes in cognition and its neural mechanisms, assuming that variation in these
      traits is heritable. Here, we focus on two species of food-caching chickadees
      (genus Poecile), which rely on stored food for survival over winter and require
      the use of spatial memory to recover their stores. These species also exhibit
      extensive climate-related population level variation in spatial memory and the
      hippocampus, including volume, the total number and size of neurons, and adults'
      rates of neurogenesis. Such variation could be driven by several mechanisms
      within the context of natural selection, including independent, population
      specific selection (local adaptation), environment experience-based plasticity,
      developmental differences, and/or epigenetic differences. Extensive data on
      cognition, brain morphology, and behavior in multiple populations of these two
      species of chickadees along longitudinal, latitudinal, and elevational gradients
      in winter climate are most consistent with the hypothesis that natural selection
      drives the evolution of local adaptations associated with spatial memory
      differences among populations. Conversely, there is little support for the
      hypotheses that environment-induced plasticity or developmental differences are
      the main causes of population differences across climatic gradients. Available
      data on epigenetic modifications of memory ability are also inconsistent with the
      observed patterns of population variation, with birds living in more stressful
      and harsher environments having better spatial memory associated with a larger
      hippocampus and a larger number of hippocampal neurons. Overall, the existing
      data are most consistent with the hypothesis that highly predictable differences
      in winter climate drive the evolution and maintenance of differences among
      populations both in cognition and in the brain via local adaptations, at least in
      food-caching parids. 

PMID- 25964498
TI  - Amygdala processing of social cues from faces: an intracrebral EEG study.
AB  - The amygdala is a key structure for monitoring the relevance of environmental
      stimuli. Yet, little is known about the dynamics of its response to primary
      social cues such as gaze and emotion. Here, we examined evoked amygdala responses
      to gaze and facial emotion changes in five epileptic patients with intracerebral
      electrodes. Patients first viewed a neutral face that would then convey social
      cues: it turned either happy or fearful with or without gaze aversion. This
      social cue was followed by a laterally presented target, the detection of which
      was faster if it appeared in a location congruent with the averted gaze
      direction. First, we observed pronounced evoked amygdala potentials to the
      initial neutral face. Second, analysis of the evoked responses to the cue showed
      an early effect of gaze starting at 123 ms in the right amygdala. Differential
      effects of fearful vs happy valence were individually present but more variable
      in time and therefore not observed at group-level. Our study is the first to
      demonstrate such an early effect of gaze in the amygdala, in line with its
      particular behavioral relevance in the spatial attention task.

PMID- 25964499
TI  - Monetary reward suppresses anterior insula activity during social pain.
AB  - Social pain after exclusion by others activates brain regions also involved in
      physical pain. Here we evaluated whether monetary reward could compensate for the
      negative feeling of social pain in the brain. To address this question we used
      the unique technique of intracranial electroencephalography in subjects with drug
      resistant epilepsy. Specifically, we recorded theta activity from intracranial
      electrodes implanted in the insular cortex while subjects experienced conditions
      of social inclusion and exclusion associated with monetary gain and loss. Our
      study confirmed that theta rhythm in the insular cortex is the neural signature
      of social exclusion. We found that while monetary gain suppresses the effect of
      social pain in the anterior insula, there is no such effect in the posterior
      insula. These results imply that the anterior insula can use secondary reward
      signals to compensate for the negative feeling of social pain. Hence, here we
      propose that the anterior insula plays a pivotal role in integrating
      contingencies to update social pain feelings. Finally, the possibility to
      modulate the theta rhythm through the reward system might open new avenues of
      research for treating pathologies related to social exclusion. 

PMID- 25964500
TI  - Post-traumatic stress and age variation in amygdala volumes among youth exposed
      to trauma.
AB  - Theoretically, normal developmental variation in amygdala volumes may be altered
      under conditions of severe stress. The purpose of this article was to examine
      whether posttraumatic stress moderates the association between age and amygdala
      volumes in youth exposed to traumatic events who are experiencing symptoms of
      post-traumatic stress disorder (PTSD). Volumetric imaging was conducted on two
      groups of youth aged 9-17 years: 28 with exposure to trauma and PTSD symptoms
      (boys = 15, girls = 13) and 26 matched (age, IQ) comparison youth (Controls; boys
      = 12, girls = 14). There was a significant group by age interaction in predicting
      right amygdala volumes. A positive association between age and right amygdala
      volumes was observed, but only in PTSD youth. These associations with age
      remained when controlling for IQ, total brain volumes and sex. Moreover, older
      youth with PTSD symptoms had relatively larger right amygdala volumes than
      controls. Findings provide evidence that severe stress may influence age-related
      variation in amygdala volumes. Results further highlight the importance of
      utilizing age as an interactive variable in pediatric neuroimaging research, in
      so far as age may act as an important moderator of group differences. 

PMID- 25964501
TI  - Supporting the self-concept with memory: insight from amnesia.
AB  - We investigated the extent to which personal semantic memory supports the self
      concept in individuals with medial temporal lobe amnesia and healthy adults.
      Participants completed eight 'I Am' self-statements. For each of the four highest
      ranked self-statements, participants completed an open-ended narrative task,
      during which they provided supporting information indicating why the I Am
      statement was considered self-descriptive. Participants then completed an
      episodic probe task, during which they attempted to retrieve six episodic
      memories for each of these self-statements. Supporting information was scored as
      episodic, personal semantic or general semantic. In the narrative task, personal
      semantic memory predominated as self-supporting information in both groups. The
      amnesic participants generated fewer personal semantic memories than controls to
      support their self-statements, a deficit that was more pronounced for trait
      relative to role self-statements. In the episodic probe task, the controls
      primarily generated unique event memories, but the amnesic participants did not.
      These findings demonstrate that personal semantic memory, in particular
      autobiographical fact knowledge, plays a critical role in supporting the self
      concept, regardless of the accessibility of episodic memories, and they highlight
      potential differences in the way traits and roles are supported by personal
      memory. 

PMID- 25964503
TI  - Factor Structure and Stability of Smoking-Related Health Beliefs in the National
      Lung Screening Trial.
AB  - INTRODUCTION: Absolute and comparative risk perceptions, worry, perceived
      severity, perceived benefits, and self-efficacy are important theoretical
      determinants of tobacco use, but no measures have been validated to ensure the
      discriminant validity as well as test-retest reliability of these measures in the
      tobacco context. The purpose of the current study is to examine the reliability
      and factor structure of a measure assessing smoking-related health cognitions and
      emotions in a national sample of current and former heavy smokers in the National
      Lung Screening Trial. METHODS: A sub-study of the National Lung Screening Trial
      assessed current and former smokers' (age 55-74; N = 4379) self-reported health
      cognitions and emotions at trial enrollment and at 12-month follow-up. Items were
      derived from the Health Belief Model and Self-Regulation Model. RESULTS: An
      exploratory factor analysis of baseline responses revealed a five-factor
      structure for former smokers (risk perceptions, worry, perceived severity,
      perceived benefits, and self-efficacy) and a six-factor structure for current
      smokers, such that absolute risk and comparative risk perceptions emerged as
      separate factors. A confirmatory factor analysis of 12-month follow-up responses
      revealed a good fit for the five latent constructs for former smokers and six
      latent constructs for current smokers. Longitudinal stability of these constructs
      was also demonstrated. CONCLUSIONS: This is the first study to examine tobacco
      related health cognition and emotional constructs over time in current and former
      heavy smokers undergoing lung screening. This study found that the theoretical
      constructs were stable across time and that the factor structure differed based
      on smoking status (current vs. former).

PMID- 25964502
TI  - Reappraising the voices of wrath.
AB  - Cognitive reappraisal recruits prefrontal and parietal cortical areas. Because of
      the near exclusive usage in past research of visual stimuli to elicit emotions,
      it is unknown whether the same neural substrates underlie the reappraisal of
      emotions induced through other sensory modalities. Here, participants reappraised
      their emotions in order to increase or decrease their emotional response to angry
      prosody, or maintained their attention to it in a control condition. Neural
      activity was monitored with fMRI, and connectivity was investigated by using
      psychophysiological interaction analyses. A right-sided network encompassing the
      superior temporal gyrus, the superior temporal sulcus and the inferior frontal
      gyrus was found to underlie the processing of angry prosody. During reappraisal
      to increase emotional response, the left superior frontal gyrus showed increased
      activity and became functionally coupled to right auditory cortices. During
      reappraisal to decrease emotional response, a network that included the medial
      frontal gyrus and posterior parietal areas showed increased activation and
      greater functional connectivity with bilateral auditory regions. Activations
      pertaining to this network were more extended on the right side of the brain.
      Although directionality cannot be inferred from PPI analyses, the findings
      suggest a similar frontoparietal network for the reappraisal of visually and
      auditorily induced negative emotions. 

PMID- 25964504
TI  - The Kraepelinian Dichotomy From the Perspective of Prenatal Infectious and
      Immunologic Insults.
AB  - The "Kraepelinian dichotomy" between schizophrenia (SZ) and bipolar disorder (BD)
      has been a dominant force in our thinking on the classification of these mental
      disorders. Emerging evidence indicates that these 2 disorders overlap
      significantly with regard to epidemiology, clinical presentation, genetic
      susceptibility, structural neuroanatomy, and treatment. Prenatal infection and
      immunologic dysfunction appear to be risk factors for both SZ and BD; some of
      these gestational exposures are present in both disorders while others may be
      specific to 1 or the other of the 2 syndromes. In this paper, we shall review
      prior studies of prenatal infections and immunologic insults in schizophrenia and
      BD, including exposures which overlap and which differ between these disorders,
      discuss the potential utility of maternal infection as one strategy toward
      developing a more biologically meaningful diagnostic classification system, and
      propose new recommendations for future research aimed at dissecting these 2
      disorders from one another at the etiologic level. 

PMID- 25964505
TI  - Predicting Methylphenidate Response in ADHD Using Machine Learning Approaches.
AB  - BACKGROUND: There are no objective, biological markers that can robustly predict
      methylphenidate response in attention deficit hyperactivity disorder. This study
      aimed to examine whether applying machine learning approaches to pretreatment
      demographic, clinical questionnaire, environmental, neuropsychological,
      neuroimaging, and genetic information can predict therapeutic response following
      methylphenidate administration. METHODS: The present study included 83 attention
      deficit hyperactivity disorder youth. At baseline, parents completed the ADHD
      Rating Scale-IV and Disruptive Behavior Disorder rating scale, and participants
      undertook the continuous performance test, Stroop color word test, and resting
      state functional MRI scans. The dopamine transporter gene, dopamine D4 receptor
      gene, alpha-2A adrenergic receptor gene (ADRA2A) and norepinephrine transporter
      gene polymorphisms, and blood lead and urine cotinine levels were also measured.
      The participants were enrolled in an 8-week, open-label trial of methylphenidate.
      Four different machine learning algorithms were used for data analysis. RESULTS:
      Support vector machine classification accuracy was 84.6% (area under receiver
      operating characteristic curve 0.84) for predicting methylphenidate response. The
      age, weight, ADRA2A MspI and DraI polymorphisms, lead level, Stroop color word
      test performance, and oppositional symptoms of Disruptive Behavior Disorder
      rating scale were identified as the most differentiating subset of features.
      CONCLUSIONS: Our results provide preliminary support to the translational
      development of support vector machine as an informative method that can assist in
      predicting treatment response in attention deficit hyperactivity disorder, though
      further work is required to provide enhanced levels of classification
      performance.

PMID- 25964506
TI  - Delayed linkage to care in one-third of HIV-positive individuals in the
      Netherlands.
AB  - OBJECTIVES: To determine time to linkage to HIV care following diagnosis and to
      identify risk factors for delayed linkage. METHODS: Patients newly diagnosed with
      HIV at sexually transmitted infections (STI) clinics in the Netherlands were
      followed until linkage to care. Data were collected at the time of diagnosis and
      at first consultation in care, including demographics, behavioural information,
      CD4+ counts and HIV viral load (VL) measurements. Delayed linkage to care was
      defined as >4 weeks between HIV diagnosis and first consultation. RESULTS: 310
      participants were included; the majority (90%) being men who have sex with men
      (MSM). For 259 participants (84%), a date of first consultation in care was
      known; median time to linkage was 9 days (range 0-435). Overall, 95 (31%) of the
      participants were not linked within 4 weeks of diagnosis; among them, 44 were
      linked late, and 51 were not linked at all by the end of study follow-up. Being
      young (<25 years), having non-Western ethnicity or lacking health insurance were
      independently associated with delayed linkage to care as well as being referred
      to care indirectly. Baseline CD4+ count, VL, perceived social support and stigma
      at diagnosis were not associated with delayed linkage. Risk behaviour and CD4+
      counts declined between diagnosis and linkage to care. CONCLUSIONS: Although most
      newly diagnosed patients with HIV were linked to care within 4 weeks, delay was
      observed for one-third, with over half of them not yet linked at the end of
      follow-up. Vulnerable subpopulations (young, uninsured, ethnic minority) were at
      risk for delayed linkage. Testing those at risk is not sufficient, timely linkage
      to care needs to be better assured as well.

PMID- 25964507
TI  - Abnormal Myocardial Function Is Related to Myocardial Steatosis and Diffuse
      Myocardial Fibrosis in HIV-Infected Adults.
AB  - BACKGROUND: Impaired cardiac function persists in the era of effective human
      immunodeficiency virus (HIV) therapy, although the etiology is unclear. We used
      magnetic resonance imaging (MRI) to measure intramyocardial lipid levels and
      fibrosis as possible contributors to HIV-associated myocardial dysfunction.
      METHODS: A cross-sectional study of 95 HIV-infected and 30 matched-healthy
      adults, without known cardiovascular disease (CVD) was completed. Intramyocardial
      lipid levels, myocardial fibrosis, and cardiac function (measured on the basis of
      strain) were quantified by MRI. RESULTS: Systolic function was significantly
      decreased in HIV-infected subjects as compared to controls (mean radial strain
      [+/-SD], 21.7 +/- 8.6% vs 30.5 +/- 14.2%; P = .004). Intramyocardial lipid level
      and fibrosis index were both increased in HIV-infected subjects as compared to
      controls (P <= .04 for both) and correlated with the degree of myocardial
      dysfunction measured by strain parameters. Intramyocardial lipid levels
      correlated positively with antiretroviral therapy duration and visceral
      adiposity. Further, impaired myocardial function was strongly correlated with
      increased monocyte chemoattractant protein 1 levels (r = 0.396, P = .0002) and
      lipopolysaccharide binding protein levels (r = 0.25, P = .02). CONCLUSIONS: HIV
      infected adults have reduced myocardial function as compared to controls in the
      absence of known CVD. Decreased cardiac function was associated with abnormal
      myocardial tissue composition characterized by increased lipid levels and diffuse
      myocardial fibrosis. Metabolic alterations related to antiretroviral therapy and
      chronic inflammation may be important targets for optimizing long-term
      cardiovascular health in HIV-infected individuals.

PMID- 25964508
TI  - Life satisfaction of musicians with focal dystonia.
AB  - BACKGROUND: Little is known about the effects of musicians' dystonia (MD) on
      patients' life satisfaction. AIMS: To assess general life satisfaction in
      patients with MD with regard to their health and jobs, in relation to the
      duration and course of the condition. METHODS: We asked patients with MD and a
      group of healthy musicians (controls) to complete a life satisfaction
      questionnaire. We analysed responses from those who had to change their
      profession and those who did not, and we assessed life satisfaction scores in
      relation to the duration and the course of the condition. RESULTS: Of the 642
      patients contacted, 295 responded (46%). We excluded 52 amateur musicians and
      analysed a sample of 243 patients with MD. We contacted an unknown number of
      healthy musicians and 57 responded. We found no differences in life satisfaction
      between patients and controls or between patients who had to change their
      profession and those who did not and no correlations between life satisfaction
      and the duration or the course of the disease. CONCLUSIONS: Musicians find a way
      to cope with dystonia, irrespective of the course of the disease or a change of
      profession. Patients should be made aware of self-regulatory mechanisms and the
      probability of being able to cope and be supported in selecting their goals and
      achieving them.

PMID- 25964509
TI  - Associations of work ability with frequent and long-term sickness absence.
AB  - BACKGROUND: Reduced work ability is related to long-term sickness absence. The
      relationship between work ability and frequent sickness absence has not
      previously been investigated. It is important to distinguish between frequent and
      long-term sickness absence as they are outcomes of different processes. AIMS: To
      investigate the associations of work ability with frequent short-term (three or
      more episodes lasting <2 weeks in the past year), long-term (one or more episodes
      lasting at least 2 weeks in the past year) and combined (frequent and long-term)
      sickness absence. METHODS: In 2010-12, we invited employees working in different
      economic sectors to complete a postal questionnaire measuring work ability using
      the work ability index (WAI). We compared the WAI scores in employees with
      frequent, long-term and combined sickness absence with the scores in employees
      without such sickness absence by multinomial regression analysis. RESULTS: Of
      6682 invited employees, 3660 (55%) completed the questionnaire. Mean (standard
      deviation) WAI scores were 41.2 (3.4), 39.4 (3.9), 37.2 (5.2) and 43.2 (2.7) in
      employees with frequent, long-term, combined sickness absence and neither
      frequent nor long-term sickness absence, respectively. WAI scores were negatively
      related to frequent (odds ratio [OR] = 0.85; 95% confidence interval [CI] 0.82
      0.88), long-term (OR = 0.79; 95% CI 0.75-0.82) and combined sickness absence (OR
      = 0.74; 95% CI 0.71-0.77). CONCLUSIONS: Self-reported reduced work ability is
      associated with both frequent and long-term sickness absence, suggesting that
      frequent sickness absence is not only driven by motivational processes.

PMID- 25964510
TI  - A questionnaire to measure medical students' attitudes towards occupational
      medicine.
AB  - BACKGROUND: Occupational medicine is not well represented in medical curricula.
      Educational programmes should aim at raising the interest of medical students in
      occupational medicine. AIMS: To develop a questionnaire to measure the attitude
      of medical students towards occupational medicine. METHODS: We drew up statements
      about attitudes. We used a 5-point Likert scale to elicit answers from second
      year medical students. We analysed the questionnaires with exploratory factor
      analysis to find common scales. After item reduction, we used the questionnaire
      in third-year medical students from another medical faculty, before and after
      education. RESULTS: Responses from 141 second-year and 208 third-year medical
      students were available. Analysis resulted in 18 statements in three scales: a
      career as an occupational physician, occupational medicine as an interesting
      speciality and role of the occupational physician. We measured modest changes
      following an occupational medicine programme. Further development of the
      questionnaire with qualitative research will lead to better usability.
      CONCLUSIONS: This questionnaire can be used to measure attitude towards
      occupational medicine; however, this questionnaire needs to be developed further.

PMID- 25964511
TI  - Differential diagnosis at admission between Takotsubo cardiomyopathy and acute
      apical-anterior myocardial infarction in postmenopausal women.
AB  - BACKGROUND: Takotsubo cardiomyopathy (TTC) typically affects postmenopausal women
      and clinically presents with chest pain, ST-segment elevation, elevated cardiac
      enzymes and apical left ventricular (LV) wall motion abnormalities that mimic
      'apical-anterior' acute myocardial infarction (AMI). This study assessed whether
      at-admission clinical evaluation helps in differential diagnosis between the two
      conditions. METHODS: The study compared at-admission clinical,
      electrocardiographic (ECG) and echocardiographic findings of 31 women (median age
      67 years, interquartile range (IQR) 62-76) with typical TTC and 30 women (median
      age 73 years, IQR 61-81) with apical-anterior AMI due to acute occlusion of the
      mid/distal left anterior descending coronary artery. RESULTS: Women with TTC
      significantly more often showed PR-segment depression (62% versus 3%, p<0.001), J
      waves (26% versus 3%, p=0.03), maximum ST-segment elevation ?2 mm (84% versus
      37%, p<0.001) and ST-segment elevation in lead II (42% versus 10%, p=0.01) than
      those with AMI. At multivariate analysis, PR-segment depression (odds ratio
      (OR)=37.2, 95% confidence interval (CI)=3.4-424, p=0.002) and maximum ST-segment
      elevation ?2 mm (OR=11.1, 95% CI=1.7-99.4, p=0.01) remained the only independent
      predictors of TTC and the co-existence of both parameters excluded AMI with a
      100% specificity. The two groups did not differ with regard to age, first
      troponin-I value, echocardiographic LV ejection fraction and distribution of
      hypo/akinetic LV segments. CONCLUSIONS: At-admission electrocardiogram (but no
      clinical, laboratory and echocardiographic features) allows differential
      diagnosis between TTC and apical-anterior AMI in postmenopausal women. The
      combination of PR-segment depression and mild (?2 mm) ST-segment elevation
      predicted TTC with greater accuracy than traditional parameters such as
      localisation of ST-segment elevation and reciprocal ST-segment depression.

PMID- 25964512
TI  - ANGPTL3 blockade with a human monoclonal antibody reduces plasma lipids in
      dyslipidemic mice and monkeys.
AB  - Angiopoietin-like protein 3 (ANGPTL3) is a circulating protein synthesized
      exclusively in the liver that inhibits LPL and endothelial lipase (EL), enzymes
      that hydrolyze TGs and phospholipids in plasma lipoproteins. Here we describe the
      development and testing of a fully human monoclonal antibody (REGN1500) that
      binds ANGPTL3 with high affinity. REGN1500 reversed ANGPTL3-induced inhibition of
      LPL activity in vitro. Intravenous administration of REGN1500 to normolipidemic
      C57Bl/6 mice increased LPL activity and decreased plasma TG levels by >=50%.
      Chronic administration of REGN1500 to dyslipidemic C57Bl/6 mice for 8 weeks
      reduced circulating plasma levels of TG, LDL-cholesterol (LDL-C), and HDL
      cholesterol (HDL-C) without any changes in liver, adipose, or heart TG contents.
      Studies in EL knockout mice revealed that REGN1500 reduced serum HDL-C through an
      EL-dependent mechanism. Finally, administration of a single dose of REGN1500 to
      dyslipidemic cynomolgus monkeys caused a rapid and pronounced decrease in plasma
      TG, nonHDL-C, and HDL-C. REGN1500 normalized plasma TG levels even in monkeys
      with a baseline plasma TG greater than 400 mg/dl. Collectively, these data
      demonstrate that neutralization of ANGPTL3 using REGN1500 reduces plasma lipids
      in dyslipidemic mice and monkeys, and thus provides a potential therapeutic agent
      for treatment of patients with hyperlipidemia. 

PMID- 25964514
TI  - Phytoactinopolyspora endophytica gen. nov., sp. nov., a halotolerant filamentous
      actinomycete isolated from the roots of Glycyrrhiza uralensis F.
AB  - A novel endophytic actinomycete, designated strain EGI 60009T, was isolated from
      the roots of Glycyrrhiza uralensis F. collected from Xinjiang Province, north
      west China. The isolate was able to grow in the presence of 0-9% (w/v) NaCl.
      Strain EGI 60009T had particular morphological properties: the substrate mycelia
      fragmented into rod-like elements and aerial mycelia differentiated into short
      spore chains. ll-2, 6-Diaminopimelic acid was the cell-wall diamino acid and
      rhamnose, galactose and glucose were the cell-wall sugars. MK-9(H4) was the
      predominant menaquinone. The major fatty acids of strain EGI 60009T were iso-C15
      : 0, anteiso-C15 : 0, anteiso-C17 : 0, iso-C17 : 0, iso-C17 : 1 and I/anteiso-C17
      : 0 B. Mycolic acids were absent. The DNA G+C content of strain EGI 60009T was
      70.4 mol%. Phylogenetic analysis based on the 16S rRNA gene sequence indicated
      that strain EGI 60009T belongs to the family Jiangellaceae and formed a distinct
      clade in the phylogenetic tree. 16S rRNA gene sequence similarities between
      strain EGI 60009T and other members of the genera Jiangella and
      Haloactinopolyspora were 96.1-96.4 and 95.7-96.0%, respectively. Based on these
      results and supported by morphological, physiological and chemotaxonomic data and
      numerous phenotypic differences, a novel species of a new genus,
      Phytoactinopolyspora endophytica gen. nov., sp. nov., is proposed. The type
      strain of Phytoactinopolyspora endophytica is EGI 60009T ( = KCTC 29657T =
      CPCC204078T).

PMID- 25964513
TI  - Increased plasma cholesterol esterification by LCAT reduces diet-induced
      atherosclerosis in SR-BI knockout mice.
AB  - LCAT, a plasma enzyme that esterifies cholesterol, has been proposed to play an
      antiatherogenic role, but animal and epidemiologic studies have yielded
      conflicting results. To gain insight into LCAT and the role of free cholesterol
      (FC) in atherosclerosis, we examined the effect of LCAT over- and underexpression
      in diet-induced atherosclerosis in scavenger receptor class B member I-deficient
      [Scarab(-/-)] mice, which have a secondary defect in cholesterol esterification.
      Scarab(-/-)*LCAT-null [Lcat(-/-)] mice had a decrease in HDL-cholesterol and a
      high plasma ratio of FC/total cholesterol (TC) (0.88 +/- 0.033) and a marked
      increase in VLDL-cholesterol (VLDL-C) on a high-fat diet. Scarab(-/-)*LCAT
      transgenic (Tg) mice had lower levels of VLDL-C and a normal plasma FC/TC ratio
      (0.28 +/- 0.005). Plasma from Scarab(-/-)*LCAT-Tg mice also showed an increase in
      cholesterol esterification during in vitro cholesterol efflux, but increased
      esterification did not appear to affect the overall rate of cholesterol efflux or
      hepatic uptake of cholesterol. Scarab(-/-)*LCAT-Tg mice also displayed a 51%
      decrease in aortic sinus atherosclerosis compared with Scarab(-/-) mice (P <
      0.05). In summary, we demonstrate that increased cholesterol esterification by
      LCAT is atheroprotective, most likely through its ability to increase HDL levels
      and decrease pro-atherogenic apoB-containing lipoprotein particles. 

PMID- 25964515
TI  - Sphingomicrobium aestuariivivum sp. nov., isolated from a tidal flat.
AB  - A Gram-stain-negative, aerobic, non-spore-forming, non-flagellated and coccoid,
      ovoid or rod-shaped bacterial strain, designated AH-M8T, was isolated from a
      tidal flat sediment collected from Aphae Island in the south-western sea, South
      Korea. Strain AH-M8T grew optimally at 35  degrees C, at pH 7.0-8.0 and in the
      presence of 2.0-3.0% (w/v) NaCl. A neighbour-joining phylogenetic tree based on
      16S rRNA gene sequences revealed that strain AH-M8T belonged to the genus
      Sphingomicrobium, clustering with the type strain of Sphingomicrobium
      astaxanthinifaciens, with which it shared 99.0% 16S rRNA gene sequence
      similarity. Sequence similarities to the type strains of other species of the
      genus Sphingomicrobium were 95.4-96.0%. Strain AH-M8T contained Q-10 as the
      predominant ubiquinone and C18 : 1omega7c, summed feature 3 (C16 : 1omega7c
      and/or C16 : 1omega6c) and C16 : 0 as the major fatty acids. The major polar
      lipids of strain AH-M8T were phosphatidylglycerol, phosphatidylethanolamine,
      sphingoglycolipid and one unidentified glycolipid. The major polyamine is
      triamine sym-homospermidine. The DNA G+C content of strain AH-M8T was 66.7 mol%
      and its mean DNA-DNA relatedness value with S. astaxanthinifaciens JCM 18551T was
      21%. The differential phenotypic properties, together with the phylogenetic and
      genetic distinctiveness, revealed that strain AH-M8T is separated from other
      species of the genus Sphingomicrobium. On the basis of the data presented, strain
      AH-M8T is considered to represent a novel species of the genus Sphingomicrobium,
      for which the name Sphingomicrobium aestuariivivum sp. nov. is proposed. The type
      strain is AH-M8T ( = KCTC 42286T = NBRC 110678T).

PMID- 25964516
TI  - Phaeodactylibacter luteus sp. nov., isolated from the oleaginous microalga
      Picochlorum sp.
AB  - A Gram-staining-negative, orange-pigmented, non-motile, aerobic bacterial strain,
      designated GYP20T, was isolated from a culture of the alga Picochlorum sp., a
      promising feedstock for biodiesel production, which was isolated from the India
      Ocean. Growth was observed at temperatures from 20 to 37  degrees C, salinities
      from 0 to 3% and pH from 5 to 9.Mg2+ and Ca2+ ions were required for growth.
      Phylogenetic analysis based on 16S rRNA gene sequencing revealed that the strain
      was a member of the genus Phaeodactylibacter, which belongs to the family
      Saprospiraceae. Strain GYP20T was most closely related to Phaeodactylibacter
      xiamenensis KD52T (95.5% sequence similarity). The major fatty acids were iso-C15
      : 1 G, iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 3. The predominant
      respiratory quinone was menaquinone-7 (MK-7). The polar lipids of strain GYP20T
      were found to consist of diphosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylglycerol, four unidentified glycolipids, two unidentified
      phospholipids and three unidentified aminolipids. According to its morphology,
      physiology, fatty acid composition and 16S rRNA sequence data, the novel strain
      most appropriately belongs to the genus Phaeodactylibacter, but can readily be
      distinguished from Phaeodactylibacter xiamenensis GYP20T. The name
      Phaeodactylibacter luteus sp. nov. is proposed with the type strain GYP20T ( =
      MCCC 1F01222T = KCTC 42180T).

PMID- 25964517
TI  - Aliiroseovarius pelagivivens gen. nov., sp. nov., isolated from seawater, and
      reclassification of three species of the genus Roseovarius as Aliiroseovarius
      crassostreae comb. nov., Aliiroseovarius halocynthiae comb. nov. and
      Aliiroseovarius sediminilitoris comb. nov.
AB  - A Gram-stain-negative, non-motile, aerobic and ovoid or rod-shaped bacterium,
      designated GYSW-22T, was isolated from seawater off Geoje Island in the South
      Sea, South Korea. Strain GYSW-22T grew optimally at 25  degrees C, at pH 7.0-8.0
      and in the presence of 1.0-2.0% (w/v) NaCl. Neighbour-joining, maximum-likelihood
      and maximum-parsimony phylogenetic trees based on 16S rRNA gene sequences showed
      that strain GYSW-22T and the type strains of Roseovarius crassostreae,
      Roseovarius halocynthiae and Roseovarius sediminilitoris form a coherent cluster,
      independent of phylogenetic lineages or clusters comprising the type strains of
      other species of the genus Roseovarius. Strain GYSW-22T exhibited 16S rRNA gene
      sequence similarities of 97.2, 96.6 and 96.3% to R. halocynthiae MA1-10T, R.
      crassostreae CV919-312T and R. sediminilitoris M-M10T, respectively, and of 92.6
      94.7% to the type strains of other species of the genus Roseovarius. Strain GYSW
      22T contained Q-10 as the predominant ubiquinone and C18 : 1omega7c as the major
      fatty acid. The major polar lipids were phosphatidylcholine,
      phosphatidylglycerol, one unidentified aminolipid and one unidentified lipid. The
      DNA G+C content of strain GYSW-22T was 59.0 mol% and its mean DNA-DNA relatedness
      value with R. halocynthiae MA1-10T was 15 %. On the basis of the data presented,
      we propose strain GYSW-22T represents a novel species of a new genus,
      Aliiroseovarius pelagivivens gen. nov., sp. nov. The type strain of the type
      species is GYSW-22T ( = KCTC 42459T = CECT 8811T). In this study, it is also
      proposed that Roseovarius crassostreae, Roseovarius halocynthiae and Roseovarius
      sediminilitoris be reclassified into the new genus as Aliiroseovarius
      crassostreae comb. nov. (type strain CV919-312T = ATCC BAA-1102T = DSM 16950T),
      Aliiroseovarius halocynthiae comb. nov. (type strain MA1-10T = KCTC 23462T = CCUG
      60745T) and Aliiroseovarius sediminilitoris comb. nov. (type strain M-M10T = KCTC
      23959T = CCUG 62413T), respectively.

PMID- 25964518
TI  - Vibrio salilacus sp. nov., a new member of the Anguillarum clade with six alleles
      of the 16S rRNA gene from a saline lake.
AB  - A Gram-stain-negative, catalase- and oxidase-positive, facultatively aerobic
      bacterium, strain DSG-S6T, was isolated from Dasugan Lake (salinity 3.1%, w/w),
      China. Its taxonomic position was determined by using a polyphasic approach.
      Cells of strain DSG-S6T were non-spore-forming, slightly bent rods, and motile by
      means of a single polar flagellum. Growth occurred in the presence of 0-7.0%
      (w/v) NaCl (optimum, 2.0%), at 4-35  degrees C (optimum, 30  degrees C) and at pH
      6.0-10.5 (optimum, pH 8.0-8.5). C16 : 0, C18 : 1omega7c and C16 : 1omega7c and/or
      C16 : 1omega6c were the major fatty acids. Six alleles of the 16S rRNA gene
      sharing 98.9-99.9  % similarity were detected in strain DSG-S6T, which showed
      highest 16S rRNA gene sequence similarity to Vibrio aestuarianus ATCC 35048T
      (97.7 %), then to Vibrio pacinii LMG 19999T (97.6%) and Vibrio metschnikovii CIP
      69.14T (96.8%). Multilocus sequence analysis of four housekeeping genes and 16S
      rRNA genes clearly clustered it as a member of the Anguillarum clade. Mean DNA
      DNA relatedness between strain DSG-S6T and V. aestuarianus NBRC 15629T, V.
      pacinii CGMCC 1.12557T and V. metschnikovii JCM 21189T was 20.6 +/- 2.3, 38.1 +/-
      3.5 and 24.2 +/- 2.8%, respectively. The DNA G+C content was 46.8 mol% (Tm).
      Based on the data, it is concluded that strain DSG-S6T represents a novel species
      of the genus Vibrio, for which the name Vibrio salilacus sp. nov. is proposed.
      The type strain is DSG-S6T ( = CGMCC 1.12427T = JCM 19265T).

PMID- 25964519
TI  - Staphylococcus argensis sp. nov., a novel staphylococcal species isolated from an
      aquatic environment.
AB  - A staphylocoagulase-negative, novobiocin-susceptible strain (M4S-6T) of a species
      of the genus Staphylococcus was isolated from the river Argen in Southern
      Germany. It was assigned to the genus Staphylococcus due to the presence of the
      fatty acids, ai-C15 : 0, i-C15 : 0, i-C17 : 0, ai-C17 : 0, and of menaquinone (MK
      7) in the cytoplasmic membrane, which are typical of coagulase-negative
      staphylococci. The polar lipid profile consisted of phosphatidylglycerol,
      diphosphatidylglycerol, an unknown phospholipid and an unknown glycolipid.
      Although the 16S gene sequence of strain M4S-6T revealed a 98% similarity with
      its closest relative, Staphylococcus pettenkoferi, it could be distinguished by
      several phenotypical and physiological markers. In contrast to S. pettenkoferi,
      M4S-6T was ornithine decarboxylase-positive, urease-negative and could use
      formiate and l-histidine as carbon-sources; nitrate was not reduced. Whereas S.
      pettenkoferi could grow with d(-)-mannitol, d-sorbitol, gluconic acid, l-proline,
      carboxymethylcellulose and lignosulfonate, M4S-6T was not able to grow with these
      substances. The results of 16S rRNA gene sequence analysis and of phenotypic
      testing indicated that M4S-6T was a representative of a novel species for which
      the name Staphylococcus argensis sp. nov., is proposed with the type strain M4S
      6T (DSM 29875T = CIP 110904T).

PMID- 25964520
TI  - Recent developments in radiosensitization.
AB  - Radiation therapy is essential for local tumor control for many types of cancer
      histologies. Technological advancements in recent years have allowed for precise
      irradiation of target tissues while minimizing the dose to non-target tissues. To
      enhance radiation damage to cancer cells and further limit the radiation effects
      on normal tissue, researchers have explored compounds that specifically target
      cancer cells and make them more sensitive to ionizing radiation. Recent
      radiosensitization research has focused on promising compounds that alter
      hypoxia, inhibit topoisomerases, interfere with microtubules, and activate
      caspases, among other mechanisms. Many such compounds have shown impressive
      results in pre-clinical trials against a variety of cell types, but their safety,
      efficacy and practicability in clinical trials remains to be demonstrated. This
      review seeks to provide an overview of recent research in radiosensitization,
      detailing some of the more successful compounds, and illustrating avenues for
      future research. 

PMID- 25964521
TI  - Radiation-associated Cardiac Injury.
AB  - Chest radiotherapy continues to play an important role in the treatment of breast
      cancer, Hodgkin's lymphoma, and other malignancies. Subsequent cardiac injury has
      been described involving essentially all structures of the heart, with most
      radiation-induced injury being progressive in nature. Our understanding over the
      multifactorial etiology and development of radiation-associated cardiac injury
      has advanced, leading to improved techniques aimed at decreasing cardiac
      radiation exposure and associated risks. Monitoring after radiotherapy clearly
      appears to be indicated; however, optimal recommendations regarding cardiac
      screening remain difficult to establish. 

PMID- 25964522
TI  - Randomized Trials of Systemic Medically-treated Malignant Mesothelioma: A
      Systematic Review.
AB  - Malignant pleural mesothelioma (MPM) is a rare but aggressive malignancy mainly
      localized to the pleura. Malignant mesothelioma grows highly invasive into
      surrounding tissue and has a low tendency to metastasize. The median overall
      survival (OS) of locally advanced or metastatic disease without treatment is 4-13
      months but, during recent years, improvement in survival has been achieved since
      treatment for patients with mesothelioma has improved with better palliative
      care, systemic medical treatment, surgery and improved diagnostics methods. The
      present review aims at describing available data from randomized trials
      considering systemic medical treatment for this patient category. 

PMID- 25964523
TI  - Targeted Therapy for NSCLC--A Double-edged Sword?
AB  - Advanced or metastatic non-small cell lung cancer (NSCLC) is characterised by a
      poor prognosis and few second- or third-line treatments. First-generation
      epidermal growth factor receptor (EGFR) 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, only few studies revealed improved
      overall survival (OS), and resistance often develops. Bevacizumab, a monoclonal
      antibody which targets vascular endothelium growth factor (VEGF), has been fully
      developed in NSCLC, and small-molecule tyrosin kinase inhibitors (TKIs) have been
      approved as first-line therapy for patients with advanced and metastatic NSCLC
      harbouring EGFR mutations. In addition, crizotinib, a novel inhibitor of the
      anaplastic lymphoma kinase, has been approved for second-line treatment of NSCLC.
      Several new drugs targeting not only the EGFR pathways, but also signal
      transduction cascades involved in angiogenesis and the mitogene-activated
      extracellular signal-regulated kinase kinase pathways are currently evaluated in
      phase III clinical trials. Experimental monoclonal antibodies are also currently
      undergoing phase III clinical trials and have shown promising activity which
      might help to improve the therapeutic landscape of NSCLC. However, many other
      drugs prolonged PFS, but failed to demonstrate a significant improvement of 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. Furthermore, since there are only very few trials
      that have shown a benefit from the addition of TKIs to chemotherapy, additional
      studies using this unselected approach are not recommended. Therefore, there is a
      definite need for an improved understanding of the complex mechanisms that are
      involved in TKI-mediated pathways, and for the development of validated
      predictive markers to allow a better treatment decision on the basis of the
      probability of response. This would certainly help to avoid the unnecessary use
      of potential toxic drugs in patients with known resistance and would facilitate
      the discovery of new targets and drugs on the basis of resistance mechanisms. 

PMID- 25964524
TI  - The role of human papilloma virus in urological malignancies.
AB  - Human papillomavirus (HPV) is associated with cancer of the cervix uteri, penis,
      vulva, vagina, anus and oropharynx. However, the role of HPV infection in
      urological tumors is not yet clarified. HPV appears not to play a major causative
      role in renal and testicular carcinogenesis. However, HPV infection should be
      kept in mind regarding cases of prostate cancer, as well as in a sub-group of
      patients with bladder cancer with squamous differentiation. Concerning the role
      of HPV in penile cancer incidence, it is a recognized risk factor proven in a
      large number of studies. This short review provides an update regarding recent
      literature on HPV in urological malignancies, thereby, also discussing possible
      limitations on HPV detection in urological cancer. 

PMID- 25964525
TI  - Exosome-like Extracellular Vesicles from MYCN-amplified Neuroblastoma Cells
      Contain Oncogenic miRNAs.
AB  - BACKGROUND: In recent years, evidence has accumulated indicating that both normal
      and cancer cells communicate via the release and delivery of macromolecules
      packed into extracellular membrane vesicles. MATERIALS AND METHODS: We isolated
      nano-sized extracellular vesicles from MYCN-amplified neuroblastoma cell lines
      using ultracentrifugation and exosome precipitation (Exoquick) protocols. These
      vesicles were characterized by transmission electron microscopy (TEM),
      nanoparticle tracking analysis and western blotting. Exosomal miRNA profiles were
      obtained using a reverse transcription-polymerase chain reaction (RT-PCR) ready
      to-use panel measuring a total of 742 miRNAs. RESULTS: In this study, we showed
      that MYCN-amplified neuroblastoma cell lines secrete populations of miRNAs inside
      small exosome-like vesicular particles. These particles were shown to be taken-up
      by recipient cells. By profiling the miRNA content, we demonstrated high
      expression of a group of established oncomirs in exosomes from two MYCN-amplified
      neuroblastoma cell lines. Despite the fact that other studies have demonstrated
      the ability of exosomal miRNAs both to repress mRNA targets and to stimulate Toll
      like receptor-8 (TLR8) signaling in recipient cells, we did not observe these
      effects with exosomes from MYCN-amplified neuroblastoma cells. However,
      functional enrichment analysis reveals that mRNA targets of highly expressed
      exosomal miRNAs are associated with a range of cellular and molecular functions
      related to cell growth and cell death. CONCLUSION: MYCN-amplified neuroblastoma
      cell lines secrete exosome-like particles containing oncogenic miRNAs. This work
      showed for the first time that neuroblastoma cells secrete exosome-like particles
      containing miRNAs with potential roles in cancer progression. These findings
      indicate a new way for MYCN-amplified neuroblastoma cells to interact with the
      tumor environment.

PMID- 25964526
TI  - Fast, Stable Induction of P-Glycoprotein-mediated Drug Resistance in BT-474
      Breast Cancer Cells by Stable Transfection of ABCB1 Gene.
AB  - BACKGROUND: Patients with P-glycoprotein and HER2/neu (HER2) receptor
      overexpressing breast cancer usually have poor clinical outcomes. However, there
      exist no commercially available breast cancer cell lines that are HER2/P
      glycoprotein double-positive, which limits research in this field. MATERIALS AND
      METHODS: We report on the development and characterization of a drug-resistant
      sub-line from an HER2-positive breast cancer cell line by stable transfection of
      the ATP-binding cassette (ABC) subfamily B member 1 (ABCB1) gene which encodes P
      glycoprotein. RESULTS: ABCB1 gene expression levels were higher after
      transfection, which led to a 40-fold increase in P-glycoprotein expression.
      Interestingly, the transfection of ABCB1 also led to a slight increase in HER2
      gene and protein expression levels. The transfection of ABCB1 increased the P
      glycoprotein expression levels significantly. CONCLUSION: The method used herein
      for developing this cell line is appropriate for fast, stable induction of P
      glycoprotein-mediated drug resistance compared to traditional methods. The in
      vitro cytotoxicity test suggests this cell line has cross-resistance to a wide
      range of chemotherapeutic agents.

PMID- 25964527
TI  - Early Reporting of Apoptosis by Real-time Imaging of Cancer Cells Labeled with
      Green Fluorescent Protein in the Nucleus and Red Fluorescent Protein in the
      Cytoplasm.
AB  - BACKGROUND/AIM: We previously developed PC-3 human prostate cancer cells
      expressing red fluorescent protein (RFP) in the cytoplasm and green fluorescent
      protein (GFP) linked to histone H2B expressed in the nucleus. We demonstrate in
      the present report the use of these dual-color cells for early detection of
      apoptosis in the presence of cancer chemotherapy agents. MATERIALS AND METHODS:
      Induction of apoptosis was observed by real-time imaging of cytoplasmic and
      nuclear size and shape changes and nuclear fragmentation using fluorescence
      microscopy. Apoptosis was also detected by measuring DNA fragmentation. The
      cancer chemotherapy agents paclitaxel and vinblastine were used for induction of
      apoptosis. RESULTS: When the PC-3 dual-color cells were treated with paclitaxel
      or vinblastine, cytoplasmic and nuclear size and shape changes and nuclear
      fragmentation were observed by 24 hours. The paclitaxel-treated PC-3 dual-color
      cells exhibited ring-like structures formed by the fragmented nuclei, which could
      be brightly visualized by H2B-GFP fluorescence. Apoptosis was also detected by
      the dual-color PC-3 cells by 24 hours when treated with vinblastine. However, no
      nuclear ring-like structures were formed in the PC-3 cells by vinblastine
      treatment. In contrast, DNA fragmentation could not be observed in PC-3 cells
      until 48 hours after exposure to paclitaxel. CONCLUSION: Dual-color PC-3 cells
      can serve as a simple real-time early reporter of apoptosis and as a screen for
      novel cancer therapeutics or genotoxic agents. The dual-color cell real-time
      imaging assay is a more sensitive and earlier reporter for apoptosis than the DNA
      fragmentation assay.

PMID- 25964528
TI  - Imaging the Interaction of Pancreatic Cancer and Stellate Cells in the Tumor
      Microenvironment during Metastasis.
AB  - BACKGROUND/AIM: Pancreatic stellate cells are involved in fibrosis of pancreatic
      cancer termed desmoplasia, which may contribute to both pancreatic cancer growth
      and metastasis, as well as to drug resistance. A better understanding of
      pancreatic cancer-cell interactions with stellate cells is therefore critical to
      our ability to develop effective anti-metastatic therapeutics for pancreatic
      cancer. MATERIALS AND METHODS: The human pancreatic cancer cell line XPA-1 was
      engineered to express green fluorescent protein (GFP) in the nucleus and red
      fluorescent protein (RFP) in the cytoplasm. Pancreatic stellate cells were
      engineered to express RFP. The pancreatic cancer cells and stellate cells were co
      cultured and their interaction was imaged in vitro. The pancreatic cancer cells
      and stellate cells were then co-injected in the spleen of transgenic cyan
      fluorescent protein (CFP) nude mice and imaged in liver, lung and diaphragm
      metastasis. RESULTS: The interaction of the pancreatic cancer cells expressing
      GFP in the nucleus and RFP in the cytoplasm and stellate cells expressing RFP was
      first imaged in vitro. The intimate relationship between the two cell types could
      be seen. Three hours after splenic co-injection, dual-color pancreatic cancer
      cells and pancreatic stellate cells were found distributed in the host liver. By
      28 days after splenic co-injection of the pancreatic cancer and stellate cells,
      liver metastases were observed in host CFP nude mice. Metastases were also
      observed in the lung and diaphragm. Stellate cells were observed along with the
      pancreatic cancer cells at all metastatic sites suggesting that stellate cells
      may be necessary for metastasis. With high-resolution intravital imaging afforded
      by the Olympus FV1000 confocal microscope, the interaction of the dual-colored
      pancreatic cancer cells and the RFP-expressing pancreatic stellate cells could be
      clearly imaged in the liver and other metastases, further suggesting that
      stellate cells participate in metastasis formation. CONCLUSION: Pancreatic cancer
      cells and stellate stem cells form a very close relationship and accompany each
      other to distant metastatic sties. Our hypothesis is that pancreatic stellate
      cells form a niche for metastasis of pancreatic cancer.

PMID- 25964529
TI  - The Use of Living Cancer Cells Expressing Green Fluorescent Protein in the
      Nucleus and Red Fluorescence Protein in the Cytoplasm for Real-time Confocal
      Imaging of Chromosome and Cytoplasmic Dynamics During Mitosis.
AB  - BACKGROUND/AIM: A library of dual-color fluorescent cancer cells with green
      fluorescent protein (GFP), linked to histone H2B, expressed in the nucleus and
      red fluorescent protein (RFP) expressed in the cytoplasm was previously
      genetically engineered. The aim of the current study was to use the dual-color
      cancer cells to visualize chromosome and cytoplasmic dynamics during mitosis.
      MATERIALS AND METHODS: Using an Olympus FV1000 confocal microscope, a library of
      dual-color cells from the major cancer types was cultured on plastic. The cells
      were imaged by confocal microscopy to demonstrate chromosome and cytoplasmic
      dynamics during mitosis. RESULTS: Nuclear GFP expression enabled visualization of
      chromosomes behavior, whereas simultaneous cytoplasmic RFP expression enabled
      visualization of cytoplasmic behavior during mitosis. Thus, total cellular
      dynamics can be visualized at high resolution, including individual chromosomes
      in some cases, in living dual-color cells in real time. CONCLUSION: Dual-color
      cancer cells expressing H2B-GFP in the nucleus and RFP in the cytoplasm provide
      unique tools for visualizing subcellular nuclear and cytoplasm dynamics,
      including the behavior of individual chromosomes during mitosis. The dual-color
      cells can be used to evaluate chromosomal loss or gain in real time during
      treatment with a variety of agents or as the cells are selected for increased or
      decreased malignancy in culture or in vivo. The dual color cells will be a useful
      tool to discover and evaluate novel strategies for killing cancer cells.

PMID- 25964530
TI  - Uniform Combretastatin-induced Effect on Monocytes and Neutrophils in Peripheral
      Blood but Not in Tumors.
AB  - BACKGROUND/AIM: Combretastatin A-4 phosphate (CA4P) is a vascular-disrupting
      agent which affects the level of circulating neutrophils. Since tumor-associated
      macrophages and neutrophils may collaborate, we compared the effect of CA4P
      treatment on monocytes/macrophages and neutrophils. MATERIAL AND METHODS: CDF1
      mice with a C3H mammary carcinoma foot tumor were injected intraperitoneally with
      CA4P. Blood samples were taken and tumors excised at various time-points after
      treatment. Circulating monocytes and granulocytes were detected by flow cytometry
      and the tumor levels of these cell types was estimated immunohistochemically.
      RESULTS: CA4P induced similar oscillating effects on the level of circulating
      monocytes and of neutrophils, with an initial decrease followed by an increase
      and a return to control levels at 6-h and 24-h, respectively. In tumors, only the
      macrophage level decreased significantly after treatment. CONCLUSION: CA4P
      induced similar changes in the level of circulating monocytes and neutrophils,
      but only affected the fraction of macrophages significantly.

PMID- 25964531
TI  - Analyzing the Association of Polymorphisms in the CRYBB2 Gene with Prostate
      Cancer Risk in African Americans.
AB  - BACKGROUND/AIM: Prostate cancer (PCa) shows disproportionately higher incidence
      and disease-associated mortality in African Americans. The human crystallin beta
      B2 (CRYBB2) gene has been reported as one tumor signature gene differentially
      expressed between African American and European American cancer patients. We
      investigated the role of CRYBB2 genetic variants in PCa in African Americans.
      MATERIALS AND METHODS: Subjects comprised of 233 PCa cases and 294 controls. Nine
      haplotype-tagged single nucleotide polymorphisms (SNPs) in and around the CRYBB2
      gene were genotyped by pyrosequencing. Association analyses were performed for
      PCa with adjustment for age and prostate-specific antigen (PSA), under an
      additive genetic model. RESULTS: Out of the nine SNPs examined, rs9608380 was
      found to be nominally associated with PCa (odds ratio (OR)=2.619 (95% confidence
      interval (CI)=1.156-5.935), p=0.021). rs9306412 was in strong linkage
      disequilibrium with rs9608380 that showed an association p-value of 0.077. Using
      ENCODE data, we found rs9608380 mapped to a region annotated with regulatory
      motifs, such as DNase hypersensitive sites and histone modifications. CONCLUSION:
      This is the first study to analyze the association between genetic variations in
      the CRYBB2 gene with PCa. rs9608380, associated with PCa, is a potentially
      functional variant.

PMID- 25964532
TI  - Contrast-enhanced Ultrasound Imaging of Antiangiogenic Tumor Therapy.
AB  - BACKGROUND/AIM: Anti-angiogenic treatment is a promising strategy for cancer
      therapy and is currently evaluated in clinical trials. The aim of the present
      study was to further investigate the effects of an anti-angiogenic therapy,
      inhibiting vascular endothelial growth factor (VEGF) and endothelial growth
      factor (EGF) using a tyrosine kinase inhibitor for blocking tumor angiogenesis
      and tumor progression in vivo. MATERIALS AND METHODS: Experiments were performed
      using C57/Bl6 mice (25 +/- 5 g of body weight (b.w.)) implanted with subcutaneous
      Lewis lung carcinoma (LLC-1). From day 7 till 21 after tumor cell implantation,
      animals (n=7 per group) were treated by monotherapy using ZD6474 (50 mg/kg b.w.
      per os (p.o.)) daily. A control group received only the solvent polysorbate 80.
      Using contrast enhanced ultrasound (CE-US) parameters of intra-tumoral
      microcirculation animals were examined 24 h after the last application of ZD6474.
      Moreover, subcutaneous tumor growth was measured over the whole therapy period.
      Finally, histological analyses were performed to analyze the functional vessel
      density in the tumor tissue. RESULTS: ZD6474 reduced tumor growth of LLC-1 in
      C57/Bl6 mice significantly. A significant difference of maximal signal intensity
      (DeltaSImax) and area below the intensity time curve (AUC) after antiangiogenic
      therapy was recorded in the tumor center by CE-US. Vessel density after
      hematoxyline and eosin, as well as CD31, staining showed no significant
      difference in both groups. CONCLUSION: Anti-angiogenic effects can be
      quantitatively demonstrated using CE-US imaging, which represents the spreading
      of efficient vessels in the tumor tissue, especially in the tumor center.

PMID- 25964533
TI  - High-dose Ionizing Radiation Regulates Gene Expression Changes in the MCF7 Breast
      Cancer Cell Line.
AB  - BACKGROUND: Intraoperative electron radiation therapy (IOERT) is a therapeutic
      technique which administers a single high dose of ionizing radiation immediately
      after surgical tumor removal. IOERT induces a strong stress response: both tumor
      and normal cells activating pro- and antiproliferative cell signaling pathways.
      Following treatment, several genes and factors are differently modulated,
      producing an imbalance in cell fate decision. However, the contribution of these
      genes and pathways in conferring different cell radiosensitivity and
      radioresistance needs to be further investigated, in particular after high-dose
      treatments. Despite the documented and great impact of IOERT in breast cancer
      care, and the trend for dose escalation, very limited data are available
      regarding gene-expression profiles and cell networks activated by IOERT or high
      dose treatment. The aim of the study was to analyze the main pathways activated
      following high radiation doses in order to select for potential new biomarkers of
      radiosensitivity or radioresistance, as well as to identify therapeutic targets
      useful in cancer care. MATERIALS AND METHODS: We performed gene-expression
      profiling of the MCF7 human breast carcinoma cell line after treatment with 9-
      and 23-Gy doses (conventionally used during IOERT boost and exclusive treatments,
      respectively) by cDNA microarrays. Real-Time Quantitative Reverse Transcription
      PCR (qRT-PCR), immunofluorescence and immunoblot experiments were performed to
      validate candidate IOERT biomarkers. We also conducted clonogenic tests and
      cellular senescence assays to monitor for radiation-induced effects. RESULTS: The
      analyses highlighted a transcriptome dependent on the dose delivered and a number
      of specific key genes that may be proposed as new markers of radiosensitivity.
      Cell and molecular traits observed in MCF7 cells revealed a typical senescent
      phenotype associated with cell proliferation arrest after treatments with 9- and
      23-Gy doses. CONCLUSION: In this study, we report genes and cellular networks
      activated following high-dose IOERT. The selected validated genes were used to
      design two descriptive models for each dose delivered. We believe that this study
      could contribute to the understanding over the complex mechanisms which regulate
      cell radiosensitivity and radioresistance in order to improve personalized
      radiotherapeutic treatment.

PMID- 25964534
TI  - Differential Gene Expression of the Proto-oncogene VAV3 and the Transcript
      Variant VAV3.1 in Oral Squamous Cell Carcinoma.
AB  - The VAV proteins VAV1, VAV2 and VAV3 have been identified as important molecules
      in tumorigenesis, tumor growth and cell migration. In addition to the full-length
      isoforms, a much shorter family member, VAV3.1, also known as VAV3 isoform 2, is
      known to be differentially expressed in a broad variety of tissues. Furthermore,
      VAV3.1 was shown to be down-regulated in cultured keratinocytes by the growth
      factors epidermal growth factor (EGF) EGF and transforming growth factor beta
      (TGFbeta) TGFbeta which in turn play important roles in the pathogenesis of oral
      squamous cell carcinoma (OSCC). Herein we showed that VAV3.1 is underexpressed in
      OSCC tissue samples compared to corresponding normal mucosa. We further
      demonstrated a trend of distinctive down-regulation of mRNA for VAV3.1 in tissues
      of locally advanced OSCC that have already metastasized to regional lymph nodes,
      indicating an increased malignant potential of tumors with low VAV3.1 mRNA
      expression. Moreover, in other studies a correlation between increased VAV3
      expression and cancer progression was shown. In the present study, the analyzed
      OSCC tissue samples showed no significant change of VAV3 mRNA expression. Taken
      together, our data support the hypothesis that molecular interactions and
      signaling cascades of VAV3 can be regulated or directed by the competing molecule
      VAV3.1. Additionally, discrete and different functions of VAV3.1 in metastasis
      and tumorigenesis are conceivable.

PMID- 25964536
TI  - Differential MicroRNA Expression Profiles in Primary and Recurrent Epithelial
      Ovarian Cancer.
AB  - BACKGROUND/AIM: Although it has been shown that microRNAs influence messenger RNA
      post-transcriptional control and can attribute to human tumorigenesis, little is
      known regarading the differences in microRNA expression between primary and
      recurrent epithelial ovarian cancer (EOC). The purpose of the present study was
      to assess the differential expression of microRNA between primary and recurrent
      EOC. MATERIALS AND METHODS: Between September 2013 and May 2014, the expression
      of microRNAs in tumor tissues from 5 primary and 5 recurrent EOC cases were
      analyzed. The tumor histotype was serous cystadenocarcinoma in all patients.
      Total RNA was extracted from tumor samples and microRNA expression levels were
      measured by performing microarray analysis. Expression levels were compared
      between the two groups and analyzed statistically. RESULTS: Several microRNAs
      were differentially expressed in recurrent EOC compared to primary EOC, including
      18 under-expressed microRNAs and 33 over-expressed microRNAs among 6,658 human
      microRNAs. Four specific microRNAs were the most significantly over-expressed in
      recurrent EOC: miR-551b, miR-19b, miR-196b and miR-3198. Moreover, 4 specific
      microRNAs were the most significantly down-expressed in recurrent EOC: miR-8084,
      miR-3201, miR-3613 and miR-7515. CONCLUSION: Based on our data, dysregulation of
      microRNA expression was associated with the recurrence of EOC. Moreover,
      significantly over- and down-regulated microRNAs can be useful biomarkers for the
      prediction of recurrence in EOC.

PMID- 25964535
TI  - A Comparative Analysis of Breast and Ovarian Cancer-related Gene Mutations in
      Canadian and Saudi Arabian Patients with Breast Cancer.
AB  - Previous reports have indicated that patients with breast cancer who are from the
      Eastern Province of Saudi Arabia have a different gene expression profile from
      that known for their age-matched North American population. In the present study,
      breast tumor samples from Canadian and Saudi Arabian patients were screened for
      known and unknown mutations within BRCA1 and BRCA2 as well as 21 additional
      genes, including, ATM, BARD1, CDH1, P53, EPCAM, MSH6, and RAD50, which have been
      implicated in breast and ovarian cancer predisposition. A total of 129 non
      synonymous mutations were identified by Ion Torrent amplicon sequencing. Forty
      one mutations in 18 genes were unique to the Canadian population and 59 mutations
      in 20 genes were unique to the Saudi Arabian population. A total of 55/129 unique
      mutations in 22 genes were not previously reported in the database. Twenty-nine
      mutations in 16 genes were common to both populations; one of these mutations was
      not previously reported in the database. The most frequently mutated gene in both
      populations was the BRCA2 gene, followed by BRCA1 and TP53. Unique to this work
      is the identification of mutations frequently found in the Saudi Arabian
      population that are rare in the Canadian population. This work will allow
      direction of genetic analysis resources toward the clinical needs of each
      particular population. 

PMID- 25964537
TI  - Down-regulation of Immune-related Genes by PSCA in Gallbladder Cancer Cells
      Implanted into Mice.
AB  - BACKGROUND/AIM: In previous work, we found that prostate stem cell antigen (PSCA)
      gene, encoding a glycosylphosphatidylinositol-anchored protein, is a presumable
      tumor suppressor in gastric cancer and gallbladder cancer (GBC). The introduction
      of PSCA cDNA into GBC cell lines significantly suppressed tumorigenecity of cells
      in mice. The PSCA protein is thought to be involved in some form of intracellular
      signaling that remains to be elucidated. MATERIALS AND METHODS: Using
      microarrays, we conducted gene-expression profiling on tumors generated by a GBC
      cell line TGBC-1TKB, with and without expression of PSCA, which was implanted
      into mice. Genes whose expression was down-regulated by PSCA were selected, and
      their down-regulation was confirmed by real-time PCR. RESULTS: We identified
      several immune-related genes down-regulated by PSCA, including interleukin 8
      (IL8), IL1 receptor antagonist (IL1RN) and S100 calcium-binding proteins A8
      (S100A8) and A9 (S100A9). CONCLUSION: PSCA signaling may suppress tumor growth in
      vivo by modulating immunological characteristics of GBC cells.

PMID- 25964538
TI  - Reduced UDP-glucose Levels Are Associated with P-glycoprotein Over-expression in
      L1210 Cells and Limit Glucosylceramide Synthase Activity.
AB  - BACKGROUND/AIM: P-glycoprotein (Pgp) expression in neoplastic cells is known to
      reduce cell sensitivity to several cytotoxic Pgp substrates. A member of the ABC
      transporter family, Pgp, represents the most frequently described membrane efflux
      pump and its expression in neoplastic cells is responsible for multi-drug
      resistance. Several lines of evidence indicate that the expression and increased
      function of both Pgp and glucosylceramide synthase (GCS, an enzyme responsible
      for ceramide pathway de-activation in the regulation of apoptosis progression)
      enhance the resistance of Pgp-positive cells. Previously, we described a
      reduction in the uridine diphosphate (UDP)-glucose contents of mouse leukemia
      cells (R) expressing Pgp due to vincristine selection compared to parental L1210
      cells (S). The reduced availability of UDP-glucose as a glucose donor in R cell
      glycosylation reactions could limit GCS-catalyzed ceramide glycosylation.
      Consequently, the over-expression of Pgp in Pgp-positive L1210 cells may be
      associated with reduced ceramide glycosylation. MATERIALS AND METHODS: To test
      this idea, we measured the expression and activities of Pgp and GCS, UDP-glucose
      levels, cellular uptake of C12-NBD-ceramide (a fluorescent analogue of ceramide)
      and ceramide-induced cell death in S and R cells. T-cells, another Pgp-positive
      variant of L1210 cells that express Pgp due to their transfection with a gene
      encoding human Pgp were also used in this study. RESULTS: We detected
      significantly reduced levels of C12-NBD-ceramide glycosylation and reduced UDP
      glucose contents in Pgp-positive R and T-cells compared to S cells. C12-NBD
      ceramide uptake assays revealed nearly identical dynamics of uptake time
      dependency curves. The Pgp-positive L1210 variants (R and T) are more sensitive
      than Pgp-negative S cells to ceramide-induced cell damage, as measured by an
      fluorescein isothiocyanate-labeled annexin V and propidium iodide apoptosis
      necrosis kit. Short chain C2-ceramide was more effective at inducing cell damage
      than ceramide analogues with longer chains. CONCLUSION: These evidence indicates
      that the down-regulation of UDP-glucose contents in Pgp-positive L1210 cells is
      responsible for their collateral sensitivity to ceramide-induced apoptosis.

PMID- 25964539
TI  - Epithelial-mesenchymal Transition (EMT) Markers in Human Pituitary Adenomas
      Indicate a Clinical Course.
AB  - BACKGROUND/AIM: Pituitary adenomas are brain tumors with invasive properties.
      Epithelial-mesenchymal-transition (EMT) is a cellular process linked to the
      transformation to an aggressive cancer phenotype. In the present study, we
      investigated the expression of a panel of EMT markers, namely E-cadherin, N
      cadherin, SLUG, SNA1 and TWIST in a cohort of human pituitary adenomas. MATERIALS
      AND METHODS: Fresh-frozen human pituitary tumors (n=95) were collected
      immediately after surgery for histology. Gene transcripts of the EMT markers were
      quantified using quantitative-polymerase chain reaction (PCR) analysis. Levels of
      expression were analyzed against clinical, pathological, invasion and endocrine
      functions. RESULTS: Levels of E-cadherin and N-cadherin had a negative and
      positive correlation with the appearance of intratumoral cystic lesions of
      pituitary tumors. E-cadherin and TWIST were associated with tumor size and
      staging. There was a significant link between SLUG/TWIST and the destruction of
      the sella fosa bones (p<0.030). EMT markers also showed links with the endocrine
      functions of pituitary tumors. In pituitary tumors, SLUG and SNA1 had significant
      correlation with N-cadherin. CONCLUSION: EMT markers are significant indicators
      of the appearance of cystic lesions, tumor progression, bone destruction and
      endocrine functions. These markers are valuable biomarkers in assessing the
      clinical course of pituitary adenomas.

PMID- 25964540
TI  - Kaempferol Is an Anti-Inflammatory Compound with Activity towards NF-kappaB
      Pathway Proteins.
AB  - BACKGROUND: The nuclear factor kappa-light-chain-enhancer of activated B cells
      (NF-kappaB) pathway is critical in inflammation, proliferation and
      carcinogenesis. There exist three main players in this pathway. The inhibitor of
      NF-kappaB (IkappaB), IkappaB kinase (IkappaK)- NF-kappaB essential modulator
      (NEMO) complex and NF-kappaB. The IkK-NEMO complex activates NF-kappaB via
      phosphorylation of Ikappabeta and, eventually, leads to its proteasomal
      degradation. This leads to nuclear translocation of NF-kappaB and activation of
      target genes, such as cyclooxygenases and interleukins. The identification of
      anti-inflammatory compounds might be an effective strategy to target inflammatory
      disorders and cancer. MATERIALS AND METHODS: In the present investigation,
      kaempferol was investigated in terms of its effect on NF-kappaB activity with a
      SEAP-driven reporter cell line, NF-kappaB DNA binding with electromobility shift
      assay (EMSA) and translocation of NF-kappaB-p65 from cytosol to the nucleus with
      western blot in Jurkat cells. RESULTS: Kaempferol revealed anti-inflammatory
      activity, as shown in vitro and in silico. Molecular docking studies of
      kaempferol revealed comparable binding energies and similar docking poses on
      target proteins such as MG-132, a known NF-kappaB inhibitor. CONCLUSION: We
      conclude that kaempferol possesses anti-inflammatory activity.

PMID- 25964541
TI  - Preliminary Results of a Multicentre Study of the UBC Rapid Test for Detection of
      Urinary Bladder Cancer.
AB  - BACKGROUND/AIM: UBC Rapid is a test detecting fragments of cytokeratins 8 and 18
      in urine. These are cytokeratins frequently overexpressed in tumor cells. We
      present the first results of a multi-centre study using UBC Rapid in patients
      with bladder cancer and healthy controls. MATERIALS AND METHODS: Clinical urine
      samples from 92 patients with tumors of the urinary bladder (45 low-grade and 47
      high-grade tumors) and from 33 healthy controls were used. Urine samples were
      analyzed by the UBC Rapid point-of-care (POC) system and evaluated both visually
      and quantitatively using a concile Omega 100 POC reader. For visual evaluation,
      different thresholds of band intensity for considering a test as positive were
      applied. Sensitivities and specificities were calculated by contingency analyses.
      RESULTS: We found that pathological concentrations by UBC Rapid are detectable in
      urine of patients with bladder cancer. The calculated diagnostic sensitivity of
      UBC Rapid in urine was 68.1% for high-grade, but only 46.2% for low-grade tumors.
      The specificity was 90.9%. The area under the curve (AUC) after receiver-operated
      curve (ROC) analysis was 0.733. Pathological levels of UBC Rapid in urine are
      higher in patients with bladder cancer in comparison to the control group
      (p<0.0001). CONCLUSION: UBC rapid can differentiate between patients with bladder
      cancer and controls. Further studies with a greater number of patients will show
      how valuable these results are.

PMID- 25964542
TI  - Cytotoxicity of Endogenous Lipids N-acyl Dopamines and their Possible Metabolic
      Derivatives for Human Cancer Cell Lines of Different Histological Origin.
AB  - BACKGROUND/AIM: Dopamine amides of long chain fatty acids are a family of
      endogenous mammalian lipids with an unknown function; they are anti-proliferative
      for the C6 glioblastoma cell line. To assess their possible anti-cancer activity
      we evaluated their cytotoxicity for a set of cancer cell lines. MATERIALS AND
      METHODS: Anti-proliferative and cytotoxic actions of these substances were
      evaluated in HOS, IMR-32, MCF-7, Namalwa, K-562 and HEK 293 cell lines (18 h
      incubation time) using MTT and lactate dehydrogenase (LDH) tests, accordingly.
      RESULTS: All N-acyl dopamines (NADA) induced cell death in all cell lines tested
      with a 50% lethal dose (LD50) in the range of 0.5-80 MUM, except for HEK-293. For
      HEK-293 only N-arachidonoyl epinephrine demonstrated an LD50 below 100 MUM.
      CONCLUSION: According to the structure-activity relationship, N-acyl dopamines
      with an intact catechol group and a non-modified hydrophobic fatty acid residue
      are cytotoxic to cancer cell lines of various histological origins.

PMID- 25964543
TI  - Pentraxin-3 Silencing Suppresses Gastric Cancer-related Inflammation by
      Inhibiting Chemotactic Migration of Macrophages.
AB  - BACKGROUND: Chronic inflammation characterized by the recruitment and activation
      of macrophages has been implicated in the development of gastric cancer.
      MATERIALS AND METHODS: Expression of the long form of pentraxin-3 (PTX3) in
      gastric cancer cells was examined by reverse transcription-polymerase chain
      reaction and enzyme-linked immunosorbent assay. The migratory capacity of gastric
      cancer cells and chemotaxis of macrophages by PTX3 were assessed by wound-healing
      and transwell assays. PTX3 silencing using small interfering RNA (siRNA) was
      performed to confirm PTX3-mediated effects. RESULTS: We demonstrated that PTX3
      expression was elevated in human advanced gastric cancer tissues with increased
      infiltration of CD11b+ macrophages. Tumor necrosis factor-alpha increased PTX3
      expression via nuclear factor-kappa B activation in human gastric cancer cells.
      PTX3 promoted the tumor cell migratory potential, the recruitment of macrophages
      and their subsequent binding to gastric cancer cells. These effects were
      suppressed by PTX3 knockdown using siRNA. CONCLUSION: Our findings suggest that
      gastric cancer-derived PTX3 promotes macrophage recruitment, which may contribute
      to gastric cancer-related inflammation.

PMID- 25964544
TI  - Class III Beta-tubulin Expression in Non-small Cell Lung Cancer: A Predictive
      Factor for Paclitaxel Response.
AB  - AIM: In order to clarify whether class III beta-tubulin (TUBB3) is a predictive
      marker for paclitaxel (PTX) chemotherapy, chemosensitivity was examined using an
      in vitro drug sensitivity assay. PATIENTS AND METHODS: Twelve specimens from non
      small cell lung cancer (NSCLC) patients were obtained for dose-response curve
      analysis and measurement of the half-maximal effective dose (ED50) of PTX using
      the histoculture drug response assay (HDRA). Forty-one specimens were evaluated
      using the HDRA and the inhibition ratio (IR) at a concentration of 25 MUg/ml PTX
      (IR25) was measured. TUBB3 expression was evaluated by H-score in
      immunohistochemical staining. RESULTS: The ED50 of PTX was 24.5 +/- 8.06 MUg/ml.
      The median H-score was significantly higher (p=0.0076) in the high effective dose
      (HE)-group (ED50 >25 MUg/ml) than in the low effective (LE)-group (ED50 <= 25
      MUg/ml). The mean IR25 was 53.8 +/- 26.6%. The median H-score for the high
      inhibition ratio (HI)-group (IR25 >50%) was significantly higher (p=0.0337) than
      the low-inhibition ratio (LI)-group (IR25 <= 50%). CONCLUSION: High TUBB3
      expression in NSCLC appeared to correlate with lower PTX sensitivity.

PMID- 25964545
TI  - Enhanced Antiproliferative and Pro-apoptotic Activities of a Novel Curcumin
      related Compound in Jurkat Leukemia T-Cells.
AB  - BACKGROUND/AIM: Inhibition of arachidonic acid metabolism by curcumin has been
      suggested to be a key mechanism for its anti-carcinogenic action. Recently, we
      reported on the synthesis of curcumin analogues and their evaluation as selective
      COX1 inhibitors. Two compounds (HP109/HP102) were selected for evaluation of
      their anti-proliferative and pro-apoptotic potential in Jurkat T-cells. MATERIALS
      AND METHODS: Jurkat T-cells were stimulated with phorbol 12-myristate 13
      acetate/phytohemagglutinin (PMA/PHA) in the absence and presence of different
      concentrations of curcumin or HP109/HP102. Interleukin 2 (IL2) production and IL2
      promoter activity were analyzed by enzyme-linked immunosorbent assay and a
      luciferase reporter assay, respectively. Proliferation and cell viability were
      monitored by 2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5
      Carboxanilide assay, annexin -V/7-amino-actinomycin D staining and western
      blotting. RESULTS: HP102 was about 10-times more effective in blocking IL2
      synthesis compared to curcumin. Enhanced effects of HP102 were also observed in
      reducing the proliferation rate and cell viability. In contrast to HP102, HP109
      did not exhibit enhanced effects compared to curcumin. CONCLUSION: The curcumin
      analog HP102 had strongly improved the anti-proliferative and pro-apoptotic
      potential in Jurkat T-cells compared to curcumin.

PMID- 25964546
TI  - Endothelial Cells Derived from Non-malignant Tissues Are of Limited Value as
      Models for Brain Tumor Vasculature.
AB  - BACKGROUND: Human umbilical cord vein endothelial cells (HUVECs) are commonly
      chosen over freshly isolated endothelial cells from glioblastomas (GECs) due to
      accessibility and costs. MATERIALS AND METHODS: To test their suitability for in
      vitro studies, we comprehensively compared the transcriptomes and responses to
      major angiogenic cytokines of HUVECs (n=2) and GECs (n=5). Purity of GEC cultures
      was confirmed by uptake of acetylated low-density protein and immunostaining.
      RESULTS: Unsupervised analysis revealed a distinct grouping. We identified 854
      differentially expressed genes. Pathway and gene ontology enrichment analyses
      pointed to clear differences in angiogenesis and leukocyte transmigration.
      Comparing the expression of cell adhesion molecules in five major angiogenic
      cytokines revealed that HUVECs in contrast to GECs did not exhibit a previously
      described down-regulation of cell adhesion molecules upon incubation with
      transforming growth factor betas, but rather with basic fibroblast growth factor.
      CONCLUSION: Given our findings, we strongly recommend the use of GECs as model
      cells for brain tumor endothelium for experiments investigating angiogenesis and
      immunobiology.

PMID- 25964547
TI  - Demethoxycurcumin-induced DNA Damage Decreases DNA Repair-associated Protein
      Expression Levels in NCI-H460 Human Lung Cancer Cells.
AB  - Demethoxycurcumin (DMC) is a key component of Chinese medicine (Turmeric) and has
      been proven effective in killing various cancer cells. Its role in inducing
      cytotoxic effects in many cancer cells has been reported, but its role regarding
      DNA damage on lung cancer cells has not been studied in detail. In the present
      study, we demonstrated DMC-induced DNA damage and condensation in NCI-H460 cells
      by using the Comet assay and DAPI staining examinations, respectively. Western
      blotting indicated that DMC suppressed the protein levels associated with DNA
      damage and repair, such as 14-3-3sigma (an important checkpoint keeper of DNA
      damage response), DNA repair proteins breast cancer 1, early onset (BRCA1), O6
      methylguanine-DNA methyltransferase (MGMT), mediator of DNA damage checkpoint 1
      (MDC1), and p53 (tumor suppressor protein). DMC activated phosphorylated p53 and
      p-H2A.X (phospho Ser140) in NCI-H460 cells. Furthermore, we used confocal laser
      systems microscopy to examine the protein translocation. The results showed that
      DMC promotes the translocation of p-p53 and p-H2A.X from the cytosol to the
      nuclei in NCI-H460 cells. Taken together, DMC induced DNA damage and affected DNA
      repair proteins in NCI-H460 cells in vitro. 

PMID- 25964548
TI  - Combining CAL-101 with Celecoxib Enhances Apoptosis of EBV-transformed B-Cells
      Through MAPK-induced ER Stress.
AB  - BACKGROUND: Phosphoinositide-3 kinase (PI3K) inhibition attenuates proliferation
      and survival in B-cell malignancies. Celecoxib induces endoplasmic reticulum (ER)
      stress-induced apoptosis via a cyclo-oxgenase-2 (COX2)-independent manner in
      certain types of cancer cells. In the present study, we assessed the effects of
      combinations of drugs with a p110delta-specific inhibitor, CAL-101, and celecoxib
      to induce apoptosis in Epstein-Barr virus (EBV)-transformed B-cells and non
      Hodgkin's lymphoma (NHL) cells. MATERIALS AND METHODS: The apoptotic effect of
      combination treatment with CAL-101 and celecoxib on B-cell malignancies was
      determined by flow cytometry and immunoblotting. RESULTS: Exposure to CAL-101 and
      celecoxib significantly increased apoptosis, which was accompanied by the
      inactivation of AKT, Ras homolog gene family, member A (RHOA), Rho-associated
      coiled-coil containing protein kinase 1 (ROCK1), and ROCK2 as well as up
      regulation of Phosphatase and tensin homolog (PTEN). Co-treatment with CAL-101
      and celecoxib triggered the ER stress response and the down-regulation of BCL2
      and BCL-XL. SB203580, SP600125, and salubrinal effectively inhibited apoptosis
      and attenuated expression of phosphorylated protein kinase RNA-like endoplasmic
      reticulum kinase (PERK) and CCAAT-enhancer-binding protein homologous protein
      (CHOP). Levels of apoptosis signal-regulating kinase 1 (ASK1) were also increased
      after treatment with CAL-101 and celecoxib. CONCLUSION: The apoptosis of EBV
      transformed B-cells and NHL cells caused by CAL-101 and celecoxib might be
      related to inhibiting the RHOA/ROCK pathway and might also be associated with
      mitogen-activated protein kinase (MAPK)-mediated ER stress.

PMID- 25964550
TI  - Identification, Molecular Characterization and Alternative Splicing of Three
      Novel Members of the Canine Kallikrein (Klk)-related Peptidase Family.
AB  - BACKGROUND/AIM: Kallikrein-related peptidases (KLKs) comprise a serine protease
      family with prominent roles in tissue physiology and disease pathogenesis,
      including cancer. Previously, we have characterized canine Klk4-10 and -14.
      Herein, we continue our efforts by characterizing three novel members of the
      canine family, i.e. Klk11-13, and investigating their expression in mammary
      cancer. MATERIALS AND METHODS: Reverse transcription-polymerase chain reaction
      (RT-PCR) and DNA sequencing were used for investigating the expression and
      determining the nucleotide sequence of all transcripts identified, respectively.
      RESULTS: It was demonstrated that (i) unlike other Klks, (CANFA)Klk12 probably
      possesses a non-AUG translation initiation codon, (ii) all three Klks undergo
      alternative splicing, with exon 2 and 3 concurrent elimination serving as the
      most prominent event, (iii) all transcripts identified were detected in both
      tumor and normal tissues, yet with different frequencies. CONCLUSION: Having
      completed this work, Klk15 is the only gene remaining to experimentally resolve
      the entire canine Klk family. Our data lay sufficient groundwork for validation
      studies and await further incorporation into genetic/evolutionary studies with
      translational impact.

PMID- 25964549
TI  - Analyses of EGF A61G Gene Variation and Serum EGF Level on Gastric Cancer
      Susceptibility and Clinicopathological Parameters.
AB  - BACKGROUND: Epidermal growth factor (EGF) induces various biological signaling
      pathways, including proliferation and differentiation and it is the natural
      ligand of the epidermal growth factor receptor (EGFR) which is a member of
      tyrosine kinase transmembrane receptor family. EGF and EGFR control important
      processes in carcinogenesis and several differences in this signaling pathway are
      very common in certain types of cancers. In present study, we examined EGF A61G
      gene polymorphism as a marker of risk and progression in gastric cancer.
      MATERIALS AND METHODS: A total of 84 patients with gastric cancer and 146 control
      individuals were enrolled in the current study. EGF A61G gene variation was
      genotyped by using polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) analysis. RESULTS: The distribution of EGF A61G genotypes
      were different between patients with gastric cancer and controls (p=0.039). Serum
      EGF levels in gastric cancer cases were significantly lower than those in
      controls (p=0.012). There were no correlations between the serum EGF levels
      according to EGF A61G genotype and allelic distributions in patients with gastric
      cancer. CONCLUSION: Our findings suggested that EGF A61G gene variations and EGF
      serum levels might be associated with the risk of gastric cancer.

PMID- 25964551
TI  - Significant Association of Cyclo-oxygenase 2 Genotypes with Upper Tract
      Urothelial Cancer.
AB  - AIM: Reliable biomarkers are in urgent need for diagnosis, outcome prediction and
      treatment-effect monitoring for upper tract urothelial carcinomas (UTUC).
      Although up-regulation of cyclo-oxygenase 2 (COX2) is found in stroma and tumor
      cells in more than half of the patients with UTUC investigated, the genomic
      contribution of COX2 to UTUC has not been studied. The study aimed to evaluate
      the association of six polymorphic genotypes of COX2 with UTUC within a Taiwanese
      population. MATERIALS AND METHODS: A total of 218 patients with UTUC and 580
      healthy controls were genotyped for six COX2 polymorphisms, namely A-1195G, G
      765C, T+8473C, intron 1, intron 5 and intron 6, and examined for their
      association with UTUC risk. RESULTS: The distribution of genotypes of COX2 G-765C
      and intron 5 were significantly different between patient and control groups
      (p=0.0001 and 0.0016, respectively), while others were not (p>0.05). The
      haplotype analysis showed that compared to the GG/TT haplotype of COX2 G
      765C/intron 5, those carrying GG/AT variants have a significantly increased risk
      of UTUC (odds ratio=4.83, 95% confidence interval=1.79-13.06), while those
      carrying CG/TT variants have a decreased risk (odds ratio=0.26, 95% confidence
      interval=0.14-0.49). CONCLUSION: Our results suggest that individual and combined
      COX2 G-765C/intron 5 genotypes play a role in controlling COX2 expression and
      UTUC development.

PMID- 25964552
TI  - Gemcitabine Induces Radiosensitization Through Inhibition of RAD51-dependent
      Repair for DNA Double-strand Breaks.
AB  - BACKGROUND/AIM: Gemcitabine (GEM) is used in clinical chemo-radiotherapy;
      however, the mechanism that contributes to enhanced radiosensitivity by GEM is
      not fully-understood. We evaluated the effect of GEM on radiosensitization in
      pancreatic cancer cell lines. MATERIALS AND METHODS: Pancreatic cell lines PK-59
      and PK-45p were used. A total of 5 MUM GEM for 4 h were administered pre- or post
      gamma irradiation. RESULTS: Enhanced cell killing effects by GEM in radiotherapy
      were observed for pre-treatment but not post-treatment GEM. We focused on the
      dynamics of RAD51 and phospho-H2AX foci after irradiation. Significantly higher
      numbers of phospho-H2AX foci were observed in GEM pre-treated cells than in
      untreated cells after irradiation. We also found inhibition of the formation and
      degradation of RAD51 foci by GEM pre-treatment. The radiosensitizing effect of
      GEM was suppressed by knockdown of RAD51. CONCLUSION: RAD51-dependent homologous
      recombination is one of the key targets in the GEM-induced radiosensitizing
      effect.

PMID- 25964553
TI  - Azaspirene analogs inhibit the growth of human uterine carcinosarcoma in vitro
      and in vivo.
AB  - Uterine carcinosarcoma is a highly aggressive gynecological neoplasm that
      responds poorly to conventional chemotherapy and radiotherapy. Recent studies
      have shown high angiogenic activities of this tumor, hence anti-angiogenic
      approaches are expected to provide new treatment strategies for this tumor. In
      previous work, azaspirene was isolated from Neosartorya sp. fungi, and in vitro
      anti-angiogenic activities were shown. In the present study, the anti-angiogenic
      effects of azaspirene analogs, synthetic molecules with a shorter ethyl group
      replacing a hexadienyl side-chain of the natural compound, were assessed in vitro
      using human umbilical vein endothelial cells (HUVECs) co-cultured with FU-MMT-3
      human uterine carcinosarcoma cells. The anti-tumor and anti-angiogenic effects of
      these analogs were also evaluated in vivo using FU-MMT-3 xenografted tumors in
      nude mice. The azaspirene analogs inhibited the tube formation of HUVECs induced
      by FU-MMT-3 cells in vitro and significantly suppressed tumor growth in vivo
      compared to the untreated group (control). A significant reduction of the
      microvessel density in tumors was observed, in comparison to the control. No
      apparent toxicity, including body loss, was observed in any mice treated in this
      study. These azaspirene analogs may be effective against uterine carcinosarcoma,
      possibly acting via potent anti-angiogenic effects. 

PMID- 25964554
TI  - Expression of miRNAs as Important Element of Melanoma Cell Plasticity in Response
      to Microenvironmental Stimuli.
AB  - BACKGROUND: Melanoma cells form monolayers in serum-containing media, however, in
      serum-free media they form anchorage-independent spheroids. We investigated
      miRNAs differentially expressed between these culture types and identified those
      that possibly control the plasticity of melanoma cells. MATERIALS AND METHODS:
      The expression of miRNAs in melanoma cells was evaluated with microarrays, and
      certain miRNAs were validated with real-time PCR. Several bioinformatic tools
      were used to assess the involvement of identified miRNAs in cancer-related
      pathways, and to compile the results of mRNA microarray data from the same
      melanoma cells. RESULTS: A total of 19 miRNAs were differentially expressed
      between monolayers and spheroids. miRNAs up-regulated in spheroids modulated cell
      motility and migration, whereas those up-regulated in monolayers suppressed
      melanogenesis. CONCLUSION: The present study identified those miRNAs that
      participate in the regulation of melanoma cell plasticity.

PMID- 25964555
TI  - Sensitivity of neoplastic cells to senescence unveiled under standard cell
      culture conditions.
AB  - BACKGROUND: Cancer cells are typically defined as infinitely proliferating,
      whereas normal cells (except stem cells) are considered as being programmed to
      become senescent. Our data show that this characterization is misleading.
      MATERIALS AND METHODS: Multiplex Ligation-dependent Probe Amplification, TP53
      sequencing, real-time polymerase chain reaction (PCR) for MUC1 and SCGB2A2 and
      immunocytochemistry, together with senescence detection assay and real-time
      microscopic observations were used to analyze primary neoplastic cells isolated
      from prostate, breast and colorectal tumors, as well as stable cancer cell lines
      (MCF7, MDA-MB-468, SW962, SK-MEL28, NCI-H1975 and NCI-H469). RESULTS: In all
      cases of primary cancer cell cultures, in vitro conditions rapidly revealed
      senescence in the majority of cells. Two out of six stable cancer cell lines did
      not exhibit any senescence-associated-beta-Galactosidase-positive cells.
      Interestingly, four cell lines had small sub-populations of senescent cells
      (single SA-beta-Gal-positive cells). CONCLUSION: Primary neoplastic cells from
      different types of cancer (prostate, breast, colon cancer) appear to be senescent
      in vitro. Apparently, cancer cell lines that have been used for many years in
      drug-testing analyses have constantly been misleading researchers in terms of the
      general sensitivity of cancer cells to senescence.

PMID- 25964556
TI  - Expression of Formyl-peptide Receptors in Human Lung Carcinoma.
AB  - BACKGROUND/AIM: Formyl-peptide receptors (FPRs) are expressed in several tissues
      and cell types. The identification of markers involved in cell growth may further
      allow for molecular profiling of lung cancer. We investigated the possible role
      of FPRs as molecular markers in several types of lung carcinomas which is the
      main cause of cancer death worldwide. MATERIALS AND METHODS: Tumor tissue samples
      were collected from six patients affected by lung cancer. Biopsies were analyzed
      for expression of FPR isoforms both in tumoral and peritumoral tissue by real
      time polymerase chain reaction (PCR), western blot and immunofluorescence.
      RESULTS: Real-time PCR, western blot and immunofluorescence analyses showed that
      FPR expression is lower in types of human lung cancer tissues when compared to
      the surrounding peritumoral tissues. CONCLUSION: The study of the mechanistic
      basis for the control of FPR expression in normal peritumoral versus tumoral
      tissues could provide the basis for new diagnostic and therapeutic interventions.

PMID- 25964557
TI  - Aquaporin 3 Expression Predicts Survival in Patients with HER2-positive Early
      Breast Cancer.
AB  - BACKGROUND/AIM: Recent studies have revealed aquaporins (AQPs) as targets for
      novel anti-tumor therapy since they are likely to play a role in carcinogenesis,
      tumor progression and invasion. Accordingly, we analyzed the prognostic impact of
      AQP3 expression and polymorphisms in a number of patients with early breast
      cancer (EBC). MATERIALS AND METHODS: AQP3 expression was investigated on the
      basis of the immunohistochemistry of tissue microarray specimens from 447 EBC
      patients who underwent surgery between 2003 and 2008. We scored the staining
      intensity (0 through 3) and percentage of positive tumor cells (0 through 4); the
      staining score was defined as sum of these scores used to categorize the AQP3
      expression as negative (0 through 2), weak (3 through 5) or strong (6 or more).
      For AQP3 polymorphisms, seven single nucleotide polymorphisms (SNPs) (rs10813981,
      rs34391490, rs2228332, rs2227285, rs591810, rs17553719 and rs3860987) were
      selected using in silico analysis and genotyped using the Sequenom MassARRAY.
      RESULTS: A total of 180 (40.3%) patients were identified as AQP3-positive
      (staining score >2), including 86 (19.2%) cases of strong expression (stating
      score >5). In a univariate analysis, AQP3 expression was significantly associated
      with survival for the patients with HER2-over-expressing EBC. Moreover, a
      multivariate survival analysis revealed that AQP3 expression was an independent
      prognostic marker of disease-free survival (DFS): hazard ratio (HR)=3.137, 95%
      confidence interval (CI)=1.079-9.125, p=0.036; distant DFS (DDFS): HR=2.784,
      95%CI=0.921-8.414, p=0.070, for the HER2-over-expressing EBC patients. Meanwhile,
      none of selected AQP3 polymorphisms were related to AQP3 expression in tumor
      tissue or survival in the current study. CONCLUSION: AQP3 expression in tumor
      tissue may be considered as a potential prognostic marker in patients with HER2
      over-expressing EBC after curative surgery.

PMID- 25964558
TI  - Monofunctional Platinum-containing Pyridine-based Ligand Acts Synergistically in
      Combination with the Phytochemicals Curcumin and Quercetin in Human Ovarian
      Tumour Models.
AB  - With the idea that platinum compounds that bind with DNA differently than
      cisplatin may be better-able to overcome platinum resistance in ovarian tumor,
      the monofunctional platinum complex tris(imidazo(1,2-alpha)pyridine)
      chloroplatinum(II) chloride (coded as LH6) has been synthesized and investigated
      for its activity, alone and in combination with the phytochemicals curcumin and
      quercetin, against human ovarian A2780, A2780(cisR) and A2780(ZD0473R) cancer
      cell lines. LH6 is found to be more active than cisplatin against the resistant
      cell lines and its bolus combinations with curcumin and quercetin are found to
      produce more pronounced cell kill. Whereas platinum accumulation from cisplatin
      is found to increase almost linearly with time, that from LH6 reaches a maximum
      at 4 h and is somewhat lowered at 24 h. It is possible that the presence of bulky
      hydrophobic imidazo (1,2-alpha-pyridine) ligand in LH6 facilitates its rapid
      uptake through the cytoplasmic membrane. Lower platinum accumulation at 24 h than
      at 4 h for LH6 can be seen to imply that efflux processes may be more dominant as
      the period of incubation is increased. When platinum-DNA binding levels at 24 h
      are compared, cisplatin is found to be associated with the higher level in the
      parent A2780 cell line and LH6 in the resistant A2780(cisR) cell line, in line
      with greater activity of cisplatin in the parent cell line and that of LH6 in the
      resistant cell line. If the observed in vitro activity of LH6 is confirmed in
      vivo, it can be seen to have the potential for development as novel platinum
      based anticancer drug. 

PMID- 25964559
TI  - Down-regulation of Phospholipase D Stimulates Death of Lung Cancer Cells
      Involving Up-regulation of the Long ncRNA ANRIL.
AB  - Dysregulation of phospholipase D (PLD) has been found in several types of human
      cancer, but the underlying regulatory mechanism remains poorly-understood. Herein
      we found PLD inhibition in human H460 lung cancer cells has anti-tumorigenic
      effects such as stimulation of apoptosis and autophagy. In the present study, in
      order to identify the responsible key regulator of these anti-tumorigenic effects
      of PLD inhibition, we analyzed the expression levels of 90 long non-coding RNAs
      (lncRNAs). Among them, the expression level of antisense noncoding RNA in the
      INK4 locus (ANRIL) was increased up to 13.6-fold by PLD inhibition in H460 human
      lung cancer cells. Moreover, knockdown of ANRIL using its specific small
      interfering RNA significantly suppressed PLD inhibition-induced apoptosis.
      Collectively, our findings showed that ANRIL is an lncRNA responsible in anti
      tumorigenesis caused by PLD inhibition and combined incorporation of ANRIL into
      PLD inhibition-induced anti-tumorigenic signaling network could be a new
      effective therapeutic approach for controlling lung cancer. 

PMID- 25964560
TI  - Evaluation of Stem Cell Marker Expression in Canine B-Cell Lymphoma Cell Lines, B
      Cell Lymphoma-generated Spheres and Primary Samples.
AB  - BACKGROUND: Canine lymphoma has lately drawn focus as a model of human non
      Hodgkin's lymphoma due to its spontaneous occurrence and similar biological
      behavior. Cells with stem cell-like characteristics are believed to play a key
      role in therapeutic failure. Thus, an initial characterization and the
      possibility of specific detection of such cells could bear significant value.
      MATERIALS AND METHODS: Expression of 12 stem cell markers were analyzed in two
      canine B-cell lymphoma cell lines, their generated spheres, and in primary
      lymphoma samples by quantitative real-time polymerase chain reaction and
      partially by flow cytometry and immunocytochemistry. RESULTS: Expression of
      maternal embryonic leucine zipper kinase (Melk) was significantly higher in CLBL
      1, CLBL-1M and in primary B-cell lymphoma samples compared to non-neoplastic
      lymph nodes. Spheres displayed a higher expression of v-myc myelocytomatosis
      viral oncogene homolog (Myc) and lower expression of Cd44 compared to original
      cell lines and primary B-cell lymphoma samples. CONCLUSION: The results suggest a
      potential interesting role of Melk in canine B-cell lymphoma. Furthermore, the up
      regulation of Myc in serum-free-generated spheres offers interesting
      possibilities for functional assays characterizing the specific generated sub
      population.

PMID- 25964561
TI  - Amifostine Increases FAS and Caspase-3 Expression in Colonic Tissue of Irradiated
      Mice.
AB  - BACKGROUND/AIM: The aim of this study was to evaluate the expression of FASL, FAS
      and FADD and caspase-3 in oesophagus, stomach and colonic tissues of mice
      irradiated in vivo by immunohistochemistry. MATERIALS AND METHODS: A total of 48
      adult male C57BL mice were distributed into four groups: Ami(-)/Rad(-): Mice
      received 0.5 ml of 0.9% physiological saline solution (PPS) intraperitioneally
      (i.p.); Ami(+)/Rad(-): mice received amifostine (400mg/kg i.p.) freshly dissolved
      in double-distilled water; Ami(-)/Rad(+): mice received 0.5 ml of PSS i.p. 30 min
      before a single whole-body radiation dose of 7 Gy; Ami(+)/Rad(+): mice received
      0.5 ml of an aqueous solution of 400 mg/kg amifostine i.p.30 min prior to
      irradiation. All groups were assigned into subgroups sacrificed at 0.5 h, 1 h, 2
      h and 4 h after irradiation. RESULTS: In oesophagus and stomach tissues, we did
      not observe any difference between Ami(-)/ad(-), Ami(+)/Rad(-), Ami(-)/Rad(+) and
      Ami(+)/Rad(+) groups in the expression of FASL, FAS and FADD. The colonic tissue
      was the only to exhibit any difference in the expression of FAS and caspase-3
      protein in the Ami(-)/Rad(+)group at 1 and 2 h. Amifostine increased FAS and
      caspase-3 immunoexpression when compared to the control. Immunoexpression for
      FASL and FADD was not remarkably different in colonic tissue. CONCLUSION: Taken
      together, our results demonstrate that amifostine increases FAS and caspase-3
      expression in colonic tissue of irradiated mice.

PMID- 25964562
TI  - Circulating Tumour Cells in Patients with Malignant Lung Tumors Undergoing Radio
      frequency Ablation.
AB  - BACKGROUND/AIM: Radiofrequency ablation (RFA) is an increasingly utilised
      technique in patients with surgically-untreatable lesions. The effect of this
      therapy on circulating tumor cells (CTCs) is unknown. As far as we are aware of,
      this is the first study to evaluate the effects of RFA on CTCs in patients with
      malignant lung tumors immediately post-treatment. PATIENTS AND METHODS: Nine
      patients with primary or metastatic lung tumors underwent RFA therapy from June
      to November 2013. Blood samples were taken before and after RFA, and filtered
      through the ScreenCell CTC capture device. RESULTS: A general increase in CTCs in
      7 out of the 9 cases was found, the largest increases were seen in the metastatic
      group. CONCLUSION: This study demonstrates that the manipulation and ablative
      procedure of lung tumors leads to immediate dissemination of tumor cells, the
      effects of which are unknown and require further investigation.

PMID- 25964563
TI  - Lupalbigenin from Derris scandens Sensitizes Detachment-induced Cell Death in
      Human Lung Cancer Cells.
AB  - BACKGROUND/AIM: The ability of cancer cells to resist to anoikis has been shown
      to augment cancer cell metastasis in many cancers. In search for potential
      substances for anti-metastatic approaches, this study aimed to investigate
      anoikis-sensitizing activity of lupalbigenin, extracted from Derris scandens.
      MATERIALS AND METHODS: Human lung cancer cells were treated with non-cytotoxic
      concentrations of lupalbigenin in a detachment condition. Anoikis was evaluated
      at various time points using MTT viability assays. The effect of lupalbigenin on
      anchorage-independent growth was performed by soft-agar assay. The survival
      signaling proteins, as well as regulatory proteins of apoptosis and metastasis,
      were examined by western blot analysis. RESULTS: Lupalbigenin treatment
      significantly down-regulated survival proteins, including protein kinase B
      (pAKT/AKT) and extracellular signal-regulated kinase (pERK/ERK), as well as anti
      apoptotic protein B-cell lymphoma 2 (BCL-2), resulting in the enhancement of the
      cellular response to anoikis and the decrease of growth and survival in an
      anchorage-independent condition. CONCLUSION: Lupalbigenin sensitizes detachment
      induced cell death in human lung cancer cell through down-regulation of pro
      survival proteins.

PMID- 25964564
TI  - Effect of new oxicam derivatives on efflux pumps overexpressed in resistant a
      human colorectal adenocarcinoma cell line.
AB  - BACKGROUND: Oxicams are non-steroidal anti-inflammatory drugs (NSAIDs). Antitumor
      potential of NSAIDs has often been reported in literature. We studied antitumor
      activity of newly synthesized oxicam derivatives (PR17 and PR18) against
      doxorubicin-sensitive and resistant human colorectal adenocarcinoma cells (LoVo
      and LoVo/Dx). MATERIALS AND METHODS: The cytotoxicity of oxicam derivatives alone
      and in combination with doxorubicin was assessed. Inhibition of P-glycoprotein
      (ABCB1) transport activity was monitored by flow cytometry. Expression of ABCB1
      gene was analyzed by semi-quantitative reverse transcription PCR, while ABCB1
      protein expression was assessed by western blotting. RESULTS: Oxicam derivative
      PR18 was more cytotoxic to cancer cells than PR17. PR18 was observed to sensitize
      LoVo/Dx cells to doxorubicin and was identified as an effective multidrug
      resistance modulator. Additionally, ABCB1 expression was reduced in the presence
      of PR18. CONCLUSION: PR18 was identified as an effective modulator in LoVo/Dx
      resistant human colorectal adenocarcinoma cells which overexpressed ABCB1 efflux
      pump.

PMID- 25964565
TI  - Analytical anisotropic algorithm versus pencil beam convolution for treatment
      planning of breast cancer: implications for target coverage and radiation burden
      of normal tissue.
AB  - AIM: The present study aimed to investigate the implications of using the
      analytical anisotropic algorithm (AAA) for calculation of target coverage and
      radiation burden of normal tissues. Most model parameters, recommendations and
      planning guidelines associated with a certain outcome are from the era of pencil
      beam convolution (PBC) calculations on relatively simple assumptions of energy
      transport in media. Their relevance for AAA calculations that predict more
      realistic dose distributions needs to be evaluated. PATIENTS AND METHODS: Forty
      patients with left-sided breast cancer receiving 3D conformal radiation therapy
      were planned using PBC with a standard protocol with 50 Gy in 25 fractions
      according to existing re-commendations. The plans were subsequently recalculated
      with the AAA and relevant dose parameters were determined and compared to their
      PBC equivalents. RESULTS: The majority of the AAA-based plans had a significantly
      worse coverage of the planning target volume and also a higher maximum dose in
      hotspots near sensitive structures, suggesting that these criteria could be
      relaxed for AAA-calculated plans. Furthermore, the AAA predicts higher volumes of
      the ipsilateral lung will receive doses below 25 Gy and smaller volume doses
      above 25 Gy. These results indicate that lung tolerance criteria might also have
      to be relaxed for AAA planning in order to maintain the level of normal tissue
      toxicity. The AAA also predicts lower doses to the heart, thus indicating that
      this organ might be more sensitive to radiation than thought from PBC-based
      calculations. CONCLUSION: The AAA should be preferred over the PBC algorithm for
      breast cancer radiotherapy as it gives more realistic dose distributions.
      Guidelines for plan acceptance might have to be re-evaluated to account for
      differences in dose predictions in order to maintain the current levels of
      control and complication rates. The results also suggest an increased
      radiosensitivity of the heart, thus indicating that a revision of the current
      models for cardiovascular complications may be needed.

PMID- 25964566
TI  - Serum Angiopoietin-like Protein 2 Improves Preoperative Detection of Lymph Node
      Metastasis in Colorectal Cancer.
AB  - AIM: We investigated whether serum markers and clinical factors could be used to
      preoperatively predict lymph node (LN) metastasis in colorectal cancer (CRC).
      PATIENTS AND METHODS: The present study enrolled 157 curative CRC patients for
      whom preoperative serum carcinoembryonic antigen (CEA), systemic inflammatory
      markers (C-reactive protein (CRP) and angiopoietin-like protein 2 (ANGPTL2)) and
      objective preoperative clinical factors were available as indicators of
      pathological LN status. RESULTS: Specific clinical factors, including gender,
      tumor size, histopathology of biopsy sample and tumor morphology, were
      significantly correlated with LN metastases. Additionally, CEA, CRP and ANGPTL2
      levels were also predictive factors for LN status. Multivariate analysis revealed
      that clinical factors, including gender, histopathology, tumor morphology and
      ANGPTL2, were identified as independent predictive factors for LN metastases. A
      combination of clinical factors reached high predictive accuracy of LN metastases
      and, combined with clinical factors, ANGPTL2 further improved the accuracy.
      CONCLUSION: Serum ANGPTL2 improves preoperative detection of LN metastasis in
      CRC.

PMID- 25964567
TI  - Radiation-induced Chondrosarcoma of the Bladder. Case Report and Review of
      Literature.
AB  - BACKGROUND: Chondrosarcoma of the bladder is an extremely rare disease. Only five
      previously described cases are known in the medical literature. PATIENTS AND
      METHODS: We present a chondrosarcoma developed 19 years after radiation treatment
      in a 73-year-old patient. A literature search of articles published from 1984 to
      2014 was performed. RESULTS: This is the first reported case of post-radiation
      bladder chondrosarcoma. We compared the clinicopathological features of the
      previously reported cases and reviewed the medical literature of the bladder
      sarcomas and post-radiation sarcomas. CONCLUSION: The primary treatment for
      bladder mesenchymal neoplasms is surgical, preferably radical cystectomy with or
      without chemotherapy. Positive surgical margin is one of the most important
      factors negatively affecting disease-specific, recurrence-free and overall
      survival rates.

PMID- 25964568
TI  - Absolute lymphocyte count with extreme hyperleukocytosis does not have a
      prognostic impact in chronic lymphocytic leukemia.
AB  - BACKGROUND/ AIM: The prognostic significance of hyperleukocytosis in chronic
      lymphocytic leukemia (CLL) remains uncertain. The aim of the present study was to
      evaluate the clinical characteristics and outcome of patients with CLL and white
      blood count (WBC) >150*10(6)/l at the time of diagnosis. PATIENTS AND METHODS:
      Using the database of the Israeli CLL Study Group, which includes 1,507 cases, we
      identified 41 patients diagnosed with WBC >150*10(6)/l and analyzed the survival
      in the group that was 62 months compared to 174 months in patients without
      hyperleukocytosis (p<0.001). However, multivariate analysis demonstrated that the
      WBC count had no predictive value in relation to survival time. While in the
      entire patient cohort advanced age and Binet stage, presence of thrombocytopenia
      and ZAP-70 expression were independently associated with poor prognosis, these
      parameters lost their prognostic value in patients with hyperleukocytosis.
      CONCLUSION: Although our results do not confirm that high initial levels of WBC
      are independently associated with shorter survival in CLL, the clinical course in
      these cases appears to be aggressive and conventional prognostic factors are not
      valid in this patient sub-group.

PMID- 25964569
TI  - Recurrence 11 years after complete response to gemcitabine, 5-Fluorouracil, and
      Cisplatin chemotherapy followed by radiotherapy in a patient with advanced
      pancreatic cancer: a case report.
AB  - A 63-year-old man diagnosed with locally advanced pancreatic ductal
      adenocarcinoma (PDAC; stage IIa) was treated with chemotherapy (gemcitabine, 5
      fluorouracil and cisplatin) followed by radiotherapy. He had complete response by
      imaging and relapse-free survival for 11 years. However, he subsequently
      presented with local tumor recurrence and underwent pancreaticoduodenectomy
      followed by chemotherapy; a partial response was achieved. As in liver metastasis
      of colonic cancer, complete response by imaging in PDAC may not mean pathological
      complete response. We would propose the importance of adjuvant surgery for a
      patient with PDAC with complete response by imaging after chemoradiotherapy. 

PMID- 25964570
TI  - A New-Generation Fecal Immunochemical Test (FIT) Is Superior to Quaiac-based Test
      in Detecting Colorectal Neoplasia Among Colonoscopy Referral Patients.
AB  - AIM: To compare a new-generation fecal immunochemical test (FIT) with the leading
      guaiac-based test in detection of fecal occult blood (FOB) in colonoscopy
      referral patients. PATIENTS AND METHODS: A cohort of 300 patients referred for
      colonoscopy was examined by two different tests for FOB: ColonView quick test
      (CV) (FIT test for haemoglobin (Hb) and haemoglobin/haptoglobin (Hb/Hp) complex)
      and HemoccultSENSA (HS) (quaiac test for Hb). Three fecal samples were tested and
      all subjects were examined by diagnostic colonoscopy with biopsy verification.
      The test was interpreted positive if any of the three samples tested positive for
      Hb (HS test) and either Hb or Hb/Hp complex (CV test). The performance indicators
      (sensitivity (SE), specificity (SP), positive predictive value (PPV), negative
      predictive value (NPV) and area under the curve (AUC)) were calculated for both
      tests using three endpoints (adenoma (A), adenoma/carcinoma (A/AC) and carcinoma
      (AC)), collectively and were stratified according to tumor site. The two tests
      were compared regarding their sensitivity/specificity balance (AUC), using the
      receiver operating characteristics (ROC) comparison test. RESULTS: Colonoscopy
      (and biopsies) disclosed normal results in 85 (27.2%) subjects, A in 91 cases
      (30.3%) and AC in 95 (31.7%) patients. For the combined A+AC endpoint, the HS
      test had SE of 58.3% and SP of 96.5% (AUC=0.774), while the CV test had 97.2% SE
      and 85.8% SP (AUC=0.916) (p=0.0001). For the A endpoint, the difference between
      HS and CV was even more significant, AUC=0.637 and AUC=0.898, respectively
      (p=0.0001). In CV test, the Hb/Hp complex was 15% (93% vs. 78%) and 8% (96% vs.
      88%) more sensitive than Hb alone, for the A and A+AC endpoints, respectively.
      Being more stable than Hb in the feces, the Hb/Hp complex detected 100% of the
      tumors in the proximal colon, as contrasted to only 41.2% and 52.9% by the Hb of
      HS and CV test, respectively (p=0.0001). CONCLUSIONS: With its 100% SE and 95.3%
      SP for proximal colon neoplasia, as well as 98.2% SE and 95.3% SP for the distal
      neoplasia, ColonView is superior to current FIT tests on the market, recently
      shown to exhibit pooled SE of 79% and pooled SP of 94% for colorectal cancer
      (CRC) in a comprehensive meta-analysis. With these exceptional performance
      indicators, ColonView quick test should be the test-of-choice for CRC screening.

PMID- 25964571
TI  - Development and validation of a nomogram to estimate the risk of prostate cancer
      in Brazil.
AB  - AIM: To develop and validate a nomogram to estimate the probability of prostate
      cancer (PCa) in men undergoing opportunistic screening. PATIENTS AND METHODS:
      This was a cross-sectional observational study on a cohort of men screened for
      PCa at the Barretos Cancer Hospital (BCH) between January 2004 and December 2007.
      Patients' data were collected from their charts and binary logistic regression
      analyses were performed to assess the power of various factor combinations as
      predictors of the PCa risk. RESULTS: Out of the 1,313 screened men who underwent
      prostate biopsy, 553 (42.1%) had histopathological confirmation of PCa. The
      logistic regression analyses provided an area under the receiver operating
      characteristics (ROC) curve (AUC) of 0.737 (95% confidence interval (CI)=0.678
      0.796) for the best predictor combination. A nomogram was constructed to estimate
      the individual risk for PCa prior to biopsy. CONCLUSION: Our nomogram provides an
      easy and practical method, superior in performance to the traditional criteria,
      predicting the diagnosis of PCa with a reasonable accuracy.

PMID- 25964572
TI  - Impact of surgical case volume on the accuracy of preoperative staging and
      compliance with the guidelines for the management of endometrial cancer.
AB  - AIM: To assess the impact of the surgical case volume on the accuracy of
      preoperative staging and compliance with the European Society of Medical Oncology
      (ESMO) guidelines for the management of endometrial cancer (EC). PATIENTS AND
      METHODS: Centers were divided into those taking care of 20 or fewer EC cases, and
      those with more than 20 per year. RESULTS: Seventeen university teaching
      hospitals fully responded to the questionnaire. The differences between the
      preoperative assessment and postoperative risk groups were significant for all
      centers (p=0.001). However, this difference was not due to the volume of patients
      of centers (p=1.00). Lymphadenectomy was performed in 21% and 82% of patients in
      the ESMO low-risk and high-risk groups, respectively, without differences between
      centers overall and centers managing more or fewer than 20 ECs per year. For the
      ESMO intermediate-risk group, the difference was significant when taking all
      groups into account (p=0.02), but it was not significant between centers managing
      fewer than 20 ECs (85%) or more than 20 ECs (59%) per year (p=0.12). CONCLUSION:
      The accuracy of preoperative staging in EC is not improved in centers managing
      more than 20 ECs per year. Lymphadenectomy practice in the presumed low- and high
      risk groups was homogenous. In the presumed intermediate-risk group,
      lymphadenectomy practice is heterogeneous and centers managing more than 20 ECs
      tend to perform lymphadenectomy more frequently.

PMID- 25964573
TI  - Para-aortic and Pelvic Radiotherapy, an Effective and Safe Treatment in Advanced
      stage Uterine Cancer.
AB  - AIM: The present, was a feasibility study of extended-field (EF) external-beam
      radiotherapy (EBRT) and vaginal brachytherapy (VBT) given sequentially following
      complete staging and adjuvant chemotherapy for patients with advanced-stage
      endometrial carcinoma (EC). PATIENTS AND METHODS: A cohort study was carried out
      in 38 patients with stage IIIC and IVB EC treated by surgery, six cycles of
      paclitaxel-carboplatin chemotherapy followed by EF EBRT and VBT. RESULTS: A total
      of 60% of the patients had non-endometrioid histology, 45% had both pelvic and
      para-aortic lymph node metastases. Two patients experienced recurrence in the
      previously irradiated field. Five-year overall and progression-free survival were
      77% and 72.5%, respectively. Grade 1 diarrhea and grade 1 cystitis were the most
      common acute and delayed side-effects. CONCLUSION: EF EBRT and VBT following
      complete staging and adjuvant chemotherapy is a safe and effective treatment for
      patients with advanced-stage EC. Compared to historical data, our study suggests
      an improved progression-free and overall survival with acceptable acute and
      delayed side-effects.

PMID- 25964574
TI  - Relationships Between Dose Intensity, Toxicity, and Outcome in Patients with
      Oligodendroglial Tumors Treated with the PCV Regimen.
AB  - BACKGROUND/AIM: The drug combination of procarbazine, lomustine (CCNU) and
      vincristine (PCV) has been associated with efficacy in oligodendroglial gliomas
      (OG) when added to radiotherapy as the first line of treatment, despite the
      important toxicity of this treatment schedule. The aim of the present study was
      to analyze the tolerance, feasibility and impact of the dose intensity of the PCV
      regimen on outcome for patients with OG. PATIENTS AND METHODS: We retrospectively
      reviewed all patients with OG receiving PCV (CCNU=110 mg/m(2)) who were referred
      to our two Institutions. The total dose and dose adaptation, cycle delay, dose
      intensity, toxicity and discontinuation of CCNU were analyzed. Impacts on the
      outcome were evaluated. RESULTS: Between 2007 and 2011, 89 patients received PCV.
      PCV was administered at relapse in 73% of patients. Only 37% completed six
      cycles, 13.4% discontinued PCV because of toxicity, the other patients
      discontinued due to tumor progression. Cycle delay and dose reduction were
      observed for 62% and 70% patients, respectively. Grade 3 and 4 toxicities were
      observed in 38% and 8% patients, respectively. Among patients whose disease did
      not progress under the PCV regimen, discontinuation due to toxicity was
      significantly correlated to poor progression-free survival (PFS: p=0.023, hazard
      ratio=2.354) and poor overall survival (OS: p=0.021, hazard ratio=5.093). A
      factor that negatively impacted PFS was the absence of CCNU dose adaptation
      (p=0.001), while OS was negatively impacted by the absence of cycle delay
      (p=0.049) and grade 3/4 toxicities (p=0.045). CONCLUSION: Despite the efficacy of
      the PCV regimen, significant toxicity is associated with this schedule, which
      appears to impact its feasibility and efficacy. The optimal PCV schedule with the
      appropriate CCNU dose-intensity adaptation should be redefined taking into
      account this finding.

PMID- 25964575
TI  - Construction of a model for predicting creatinine clearance in Japanese patients
      treated with Cisplatin therapy.
AB  - BACKGROUND/AIM: There exist various useful predictive models, such as the
      Cockcroft-Gault model, for estimating creatinine clearance (CLcr). However, the
      prediction of renal function is difficult in patients with cancer treated with
      cisplatin. Therefore, we attempted to construct a new model for predicting CLcr
      in such patients. PATIENTS AND METHODS: Japanese patients with head and neck
      cancer who had received cisplatin-based chemotherapy were used as subjects. A
      multiple regression equation was constructed as a model for predicting CLcr
      values based on background and laboratory data. RESULTS: A model for predicting
      CLcr, which included body surface area, serum creatinine and albumin, was
      constructed. The model exhibited good performance prior to cisplatin therapy. In
      addition, it performed better than previously reported models after cisplatin
      therapy. CONCLUSION: The predictive model constructed in the present study
      displayed excellent potential and was useful for estimating the renal function of
      patients treated with cisplatin therapy.

PMID- 25964576
TI  - Positive Interplay Between CD3+ T-lymphocytes and Concurrent COX-2/EGFR
      Expression in Canine Malignant Mammary Tumors.
AB  - BACKGROUND/AIM: The ability of tumors to evade the immune system is one of cancer
      hallmarks. In breast cancer, it has been demonstrated that the cyclooxygenase
      2(+)/ epidermal growth factor receptor(+) (COX-2(+)/EGFR(+)) status might
      influence tumor microenvironment allowing escape of cancer cells to the immune
      system. This topic is unknown in canine mammary tumors (CMT). Therefore, the
      potential relationship between CD3(+) T-lymphocytes and concurrent COX-2/EGFR
      expression was investigated. MATERIALS AND METHODS: Formalin-fixed paraffin
      embedded malignant CMT samples (n=63) were submitted to immunohistochemical
      staining to detect CD3, COX-2 and EGFR. RESULTS: Tumoral CD3(+) T-lymphocytes
      were significantly associated with tubular differentiation grade (p=0.006), tumor
      necrosis (p=0.025), histological grade of malignancy (p=0.027) and presence of
      lymph node metastasis (p=0.009). A correlation between COX-2 and EGFR was
      observed (r=0.741, p<0.0001). The COX-2(+)/EGFR(+) group was associated with
      tumor size (p=0.002), mitotic index (p=0.019), histological grade of malignancy
      (p=0.035) and presence of lymph node metastasis (p=0.041). CD3(+) T-lymphocytes
      and COX-2/EGFR groups were significantly associated (p=0.025) and positively
      correlated (r=0.399; p=0.003). CONCLUSION: The present results suggest that the
      COX-2(+)/EGFR(+) status may be part of a strategy adopted by tumor cells to evade
      the cytotoxic tumor-specific immune responses.

PMID- 25964577
TI  - Significance of Hepatectomy for AJCC/UICC T3 Hepatocellular Carcinoma.
AB  - BACKGROUND: It is difficult to treat the American Joint Committee on Cancer
      (AJCC)/International Union against Cancer (UICC) T3 hepatocellular carcinoma
      (HCC), curatively. PATIENTS AND METHODS: We compared the clinicopathology of T3
      group (n=44: T3a 25, T3b 19) with that of the T1 (n=257) or T2 group (n=120) and
      evaluated favorable conditions of hepatectomy for T3 HCC patients. RESULTS: The
      T3 group had significantly higher hepatitis B surface antigen (HBsAg)-positive
      rates and better liver function. Infiltrative large tumors located beyond one sub
      segment with intrahepatic metastasis were significantly more common.
      Significantly, more non-curative large hepatectomies with transarterial
      embolization were performed. There was no significant difference between T3 and 2
      groups in 5-year disease-free survival (DFS) and survival (S). Tumor size more
      than 55 mm and serum albumin less than 3.5 g/dl were risk factors of hepatectomy
      for T3 HCC patients by multivariate analysis. CONCLUSION: Surgeons should resect
      AJCC/UICC T3 HCC lesions if the patient is able to tolerate surgery.

PMID- 25964578
TI  - Impact of Nagasaki atomic bomb exposure on myelodysplastic syndrome patients who
      are treated with azacitidine.
AB  - BACKGROUND/AIM: High-dose radiation exposure greatly increases the risk of
      myelodysplastic syndromes (MDS), however the clinical characteristics of MDS
      among atomic bomb survivors have not been thoroughly investigated to date. We
      designed this study to identify these characteristics. PATIENTS AND METHODS: We
      retrospectively evaluated data from 13 atomic bomb survivors with MDS and 15
      elderly patients with de novo MDS who were diagnosed between April 2011 and April
      2013 at the Nagasaki Genbaku Hospital. All patients were treated with azacitidine
      (AZA; a hypomethylating agent) and overall survival rates were estimated.
      RESULTS: No clear difference was observed in the clinical response to AZA between
      the two groups. However, atomic bomb survivors had a survival disadvantage,
      independent of their karyotype. CONCLUSION: Minute genetic alterations caused by
      exposure to atomic radiation can adversely affect the response to AZA, even 66
      years after the exposure. Further studies are required to clarify the mechanisms
      underlying this phenomenon.

PMID- 25964579
TI  - Nuclear survivin expression in small cell lung cancer.
AB  - BACKGROUND/AIM: Little evidence exists regarding a relationship between survivin
      expression and prognosis in small cell lung cancer (SCLC). We investigated the
      relationship between survivin expression, clinical characteristics and prognosis
      in SCLC patients. MATERIALS AND METHODS: We retrospectively reviewed medical
      records of study patients and analyzed their tumor sections using nuclear
      survivin labeling index (LI). RESULTS: A significant correlation between nuclear
      survivin LI and clinical stage was found (p=0.012). In multivariate analysis, a
      significant association was found between survival and clinical stage (hazard
      ratio (HR)=2.09; 95 % confidence interval (CI)=1.08-4.31; p=0.027) but not
      between survival and nuclear survivin LI (HR=0.96; 95 % CI=0.91-1.02; p=0.2).
      CONCLUSION: We did not find any positive relationship between nuclear survivin
      expression and survival in SCLC patients. Conversely, we found a positive
      relationship between clinical stage and nuclear survivin LI, which is considered
      to be useful in deciding treatment strategies.

PMID- 25964580
TI  - Interleukin-32 expression and Treg infiltration in esophageal squamous cell
      carcinoma.
AB  - BACKGROUND/AIM: Interleukin-32 (IL32) has been newly-identified as a
      proinflammatory cytokine. In the present study, we aimed to clarify the clinical
      role of IL32-positive cells in esophageal squamous cell cancer (ESCC) and
      regulatory T-cell (Treg) infiltration in the stroma. A total of 179 patients with
      ESCC who underwent surgical resection from 1990 to 2004 were eligible for this
      study. The expression of IL32 and the degree of stromal infiltration by Tregs
      were examined simultaneously. The association between each factor and the
      clinicopathological features was analyzed. Sixty and 74 out of 179 patients with
      ESCC were regarded as having IL32-positive tumors and many Tregs (high-Treg
      group), respectively. The IL32-positive and high-Treg groups had significantly
      deeper tumor invasion than did the IL32-negative and low-Treg groups (p<0.05, for
      both groups). The multivariate analysis indicated that a combination of IL32
      expression and presence of Tregs was one of the poor independent factors
      (p<0.05). IL32 expression and Treg infiltration in ESCC play an important
      synergistic role in tumor growth and invasion. The combination of IL32 positivity
      and degree of infiltration of Treg is a useful prognostic marker in ESCC.

PMID- 25964581
TI  - The prognostic role of claudins -1 and -4 in oral squamous cell carcinoma.
AB  - Claudin dysregulation has been described in various tumor types; however, its
      clinical relevance is poorly understood. We present a study in which we assessed
      the expression of claudin 1 (CLDN1) and CLDN4 in oral squamous cell carcinoma
      (OSCC), as well as their prognostic relevance. Immunohistochemical analysis of
      CLDN1 and CLDN4 expression was carried out on tissue sections from 65 OSCCs. The
      presence of CLDN1 in the invasive front of tumor islands was associated with neck
      node metastasis, and the expression of CLDN4 was associated with higher
      histological grade, and tumor recurrence. Membranous staining for CLDN4 in tumor
      cells, and weak intensity of CLDN4 immunoexpression were predictive for poorer
      survival. In a multivariate analysis for disease recurrence, CLDN1 immunostaining
      was statistically significant. Specifically, CDLN1 expression in the tumor
      invasive front was associated with tumor recurrence. Our results indicate that
      CLDN4 expression is correlated with poor prognosis, and CLDN1 expression may be
      an indicator of recurrence of OSCC. 

PMID- 25964582
TI  - Profile of serum factors and disseminated tumor cells before and after
      radiofrequency ablation compared to resection of colorectal liver metastases - a
      pilot study.
AB  - BACKGROUND/AIM: The degree of systemic response after hepatic radiofrequency
      ablation (RFA) has not been well-compared to liver resection so far. This pilot
      study was designed to examine whether RFA, compared to liver resection,
      significantly varies concerning dissemination of circulating tumor cells and
      induction of different pro-inflammatory markers and liver-specific growth
      factors. PATIENTS AND METHODS: Patients with colorectal liver metastases were
      treated with RFA, a combination of RFA and resection or liver resection only.
      Blood samples of 18 patients were obtained at different time points and
      interleukin (IL)-6, hepatocyte growth factor (HGF) and 70-kD heat shock protein
      (HSP70) serum levels were determined by ELISA. Circulating tumor cells were
      detected with reverse transcription-polymerase chain reaction (RT-PCR)
      amplification of cytokeratin 20 (CK20) mRNA (CK20 RT-PCR). RESULTS: The detection
      of circulating tumor cells was not significantly different, but in two patients
      RFA induced tumor cell dissemination. Serum levels of IL-6 were strongly elevated
      after the operation without any significant differences between the treatment
      groups. The HGF ratio was significantly higher after RFA+resection compared to
      resection-alone and the HSP70 ratio also showed significantly higher values after
      RFA compared to resection alone. High postoperative IL-6 and HGF levels
      negatively influenced overall survival (OS) independently of the treatment group.
      CONCLUSION: This pilot study demonstrates that RFA might influence tumor cell
      dissemination. There exist detectable differences in serum factors between RFA
      and liver resection after the operation but this did not influence the overall
      survival of the patients. For all patients, high postoperative IL-6 and HGF
      levels are negative prognostic markers.

PMID- 25964583
TI  - Additional Surgery After Non-curative Resection of ESD for Early Gastric Cancer.
AB  - AIM: The appropriate additional surgery after non-curative resection of
      Endoscopic Mucosal Resection (ESD) for early gastric cancer is herein discussed.
      PATIENTS AND METHODS: Data on 54 patients after non-curative resection of ESD
      were evaluated. These patients were broadly classified according to the risk of
      lymph node metastasis with lesions into group A (without risk) (n=26) and group B
      (with risk) (n=28). Their treatment results were evaluated. RESULTS: The
      incidence of residual lesion was 7.7% in group A and 14.3% in group B. Risk
      factors were piecemeal resection, involvement of the horizontal margin (HM1) or
      unclear involvement of the horizontal margin (HMX) and with ulceration. Lymph
      node metastasis was detected in one patient with lymphatic invasion, total
      diameter of 3 cm or more and submucosal invasion over 0.5 mm (SM2). The 5-year
      survival rate was 93% and none of the patients died of gastric cancer.
      CONCLUSION: Follow-up observation was reasonable in group A. Patients who are
      judged as having undergone piecemeal resection, HM1 or HMX and with ulceration,
      should be treated by additional surgery and patients judged with SM2 or total
      diameter of 3 cm or more or lymphatic invasion should be treated by additional
      surgery with lymphadectomy in group B.

PMID- 25964584
TI  - Induction Chemotherapy Using FAP for Patients with Stage II/III Squamous Cell
      Carcinoma of the Esophagus.
AB  - BACKGROUND: The aim of this study were to evaluate the feasibility and efficacy
      of chemotherapy using fluorouracil, adriamycin, and cisplatin (FAP) in patients
      with clinical stage II/III squamous cell carcinoma of the esophagus (SCCE).
      PATIENTS AND METHODS: Forty patients were enrolled in the study. They received 30
      mg/m(2) adriamycin and 70 mg/m(2) cisplatin on day 1, and 700 mg/m(2) 5
      fluorouracil on days 1-5 every four weeks. Following two courses of chemotherapy,
      eligible patients underwent esophagectomy. RESULTS: Twenty-one patients (53%)
      achieved partial response, and 27 patients underwent surgical resection
      (resection rate: 68%). Grade 3/4 toxicities developed: 7 patients (18%) with
      leukopenia, 23 (58%) with neutropenia. The three and five-year survival rates
      were 55% and 48%. Patients with surgical resection had better prognosis than
      those without resection, with a three-year survival rate of 68% vs. 25%.
      CONCLUSION: FAP is effective and feasible and surgery may provide additional
      benefit for SCCE patients with FAP.

PMID- 25964585
TI  - Phospholipase A2 Group III and Group X Have Opposing Associations with Prognosis
      in Colorectal Cancer.
AB  - BACKGROUND: Although secretory phospholipase A2 (sPLA2) has been shown to be
      involved in various biological processes, its specific roles in sub-types of
      cancer development remain to be elucidated. MATERIALS AND METHODS: We examined
      the expression of sPLA2 group III (GIII) in 142 patients with colorectal cancer
      using immunohistochemistry, and its correlation with clinicopathological features
      and outcomes. In addition, we examined the co-expression of sPLA2GIII and sPLA2GX
      using serial tissue sections to clarify the roles of both proteins in colorectal
      carcinogenesis. RESULTS: In 66 cases, diffuse staining of sPLA2GIII was seen;
      this was defined as the group with high expression. High expression was
      associated with a significantly higher rate of lymph node metastasis (p=0.02) and
      poorer survival (p=0.03) compared with low expression. Patients with low
      sPLA2GIII and high sPLA2GX expression had a significantly higher survival rate
      than those with high sPLA2GIII and low sPLA2GX expression (p=0.038). CONCLUSION:
      sPLA2GIII expression may be used as a risk factor for lymph node metastasis and a
      prognostic marker in colorectal cancer. In addition, sPLA2GIII and sPLA2GX may
      play opposing roles in colorectal carcinogenesis.

PMID- 25964586
TI  - Simultaneous Integrated Boost (SIB): RapidArc and Tomotherapy Plan Comparison for
      Unilateral and Bilateral Neck Irradiation.
AB  - AIM: The aim of the present study was to compare simultaneous integrated boost
      (SIB) plans using volumetric modulated arc therapy (RapidArc(r); RA) or
      tomotherapy (TT) for bilateral (BL) and unilateral (UL) treatment in head-and
      neck cancer (HNC) patients. MATERIAL AND METHODS: Seventeen computed tomography
      scans (CTs) of 16 patients with SIB were replanned using TT and RA. We defined
      three groups: All, UL and BL, compared the dose distributions, homogeneity,
      conformity to planning target volume (PTV), organs at risk (OAR) and healthy
      tissue (HT) sparing. We evaluated a therapeutic-width index (TWI) based on PTV
      coverage and parotid gland (PG) sparing. RESULTS: PTV coverage for RA and TT was
      equivalent for all groups. UL irradiation resulted in similar doses to the HT for
      both techniques but TT achieved better sparing of spinal cord, larynx and
      contralateral PGs. TT provided better homogeneity. RA gave better conformity.
      CONCLUSION: Both methods achieved clinically acceptable results for UL and BL
      treatment, RA with better dose conformity to elective PTV, TT with better OAR
      sparing and homogeneity.

PMID- 25964587
TI  - 18F-FDG-PET/CT Imaging in Patients with Febrile Neutropenia and Haematological
      Malignancies.
AB  - The aim of the present study was to assess the prevalence of hyper-metabolic
      infection sites revealed by fluorine-18 ((18)F) fluorodeoxyglucose (FDG) positron
      emission tomography (PET) combined with computed tomography (CT) in patients with
      febrile neutropenia (FN). Forty-eight consecutive patients with haematological
      malignancies and persistent FN (temperature >= 38 degrees C and neutrophil count
      <500 cells/MUl for more than two days) as a consequence of intensive chemotherapy
      were prospectively included. Pathological FDG uptakes identified 31 foci of
      infections located in the lungs (n=15, 48.4 %), colon (n=4, 12.9%), pancreas
      (n=2, 6.5%), skin (n=3, 9.7%), ear-nose-throat area (n=5, 16.1%), central venous
      catheter tract (n=1, 3.2%) and gallbladder (n=1, 3.2%). These pathological FDG
      uptakes were observed in half of the 48 patients (n=24). Among the 38 patients
      with a clinical diagnosis of infection, 23 showed a pathological FDG uptake,
      resulting in a FDG-PET/CT sensitivity of 61% (95% CI, 43-76%). Our study
      confirmed the ability of FDG-PET/CT to diagnose infections in patients with
      persistent FN.

PMID- 25964588
TI  - Rare Complex Mutational Profile in an ALK Inhibitor-resistant Non-small Cell Lung
      Cancer.
AB  - Testing for somatic alterations, including anaplastic lymphoma receptor tyrosine
      kinase gene (ALK) rearrangements and epidermal growth factor receptor gene (EGFR)
      mutations, is standard practice in the diagnostic evaluation and therapeutic
      management of non-small cell lung cancer (NSCLC), where the results of such tests
      can predict response to targeted-therapy. ALK rearrangements, EGFR mutations and
      mutations in the Kirsten rat sarcoma viral oncogene homolog (KRAS) are considered
      mutually exclusive in NSCLC. Herein we identified a KRAS Q22K mutation and
      frameshift mutations in the genes encoding serine/threonine kinase 11 (STK11) and
      ataxia telangiectasia mutated serine/threonine kinase (ATM) by next-generation
      sequencing in a patient with ALK rearrangement-positive oligo-metastatic NSCLC,
      whose disease progressed while on two ALK-targeted therapies. Such a complex
      diagnostic genetic profile has not been reported in ALK fusion-positive NSCLC.
      This case highlights the utility of comprehensive molecular testing in the
      diagnosis of NSCLC. 

PMID- 25964589
TI  - Radiation therapy for choroid plexus carcinoma patients with Li-Fraumeni
      syndrome: advantageous or detrimental?
AB  - BACKGROUND: Choroid plexus carcinomas (CPCs) are rare pediatric tumors often
      associated with Li-Fraumeni Syndrome (LFS), a germline mutation in the TP53 tumor
      suppressor gene, predisposing to cancer. MATERIALS AND METHODS: We performed a
      systemic literature review from 1990-2013 to evaluate the hypothesis that
      radiation therapy should be avoided in patients with CPC and LFS. Overall
      survival (OS) was compared using Kaplan-Meier curves and log-rank tests. RESULTS:
      Twenty-eight patients were documented with CPC and LFS. Eleven out of 17 patients
      received radiation therapy. The survival of patients receiving radiation was
      inferior to that of those without radiation [median (+/-95% confidence interval)
      2-year OS=0.18 +/- 0.12% versus 0.58 +/- 0.12%]. The log-rank tests suggested the
      difference to be marginally significant (p=0.056). CONCLUSION: This finding
      provides evidence for pursuing treatment approaches that do not include radiation
      therapy for patients with LFS.

PMID- 25964590
TI  - Thymidine kinase levels correlate with prognosis in aggressive lymphoma and can
      discriminate patients with a clinical suspicion of indolent to aggressive
      transformation.
AB  - Serum levels of thymidine kinase 1 (TK1), an enzyme involved in the G1-S phase of
      the cell cycle, have been previously shown to correlate with the prognosis of
      lymphoid malignancies. We hypothesized that TK1 levels will be higher in
      aggressive, compared to indolent lymphoproliferative, malignancies and this may
      serve as a marker of transformation from an indolent to aggressive disease. We
      analyzed serum from 182 patients and correlated the findings with the type of
      malignancy and prognosis; we further compared the TK1 levels of 31 patients with
      a proven transformation and 34 patients with clinically suspected transformation
      that was eventually deferred. The mean TK1 levels of patients with indolent and
      aggressive disease was 18.9+/-3.3 and 39.8+/-3.3 U/l respectively (p<0.001).
      Among patients with aggressive disease, low TK1 levels correlated with improved
      survival (p=0.008). TK1 levels >16.6 U/l predicted transformation from indolent
      to aggressive disease (sensitivity of 95%, specificity of 76%, negative
      predictive value (NPV) of 96% and positive predictive value (PPV) of 69%). A
      regression analysis showed that only TK1 levels were significant (relative risk
      (RR)=1.03 for each unit, confidence interval (CI)=1-1.05; p=0.015) for diagnosing
      a true transformation. In conclusion, TK levels are useful in assessing
      prognosis, especially in aggressive lymphoproliferative diseases. Moreover, TK
      levels are adequate in discriminating cases of indolent lymphoma that transformed
      to an aggressive disease from patients with no proven transformations. This tool
      provides the clinician a novel method to distinguish between symptomatic patients
      utilizing a simple test and may lessen the need for aggressive or invasive
      measures of investigation.

PMID- 25964591
TI  - Does the diagnosis center influence the prognosis of ovarian cancer patients
      submitted to neoadjuvant chemotherapy?
AB  - AIM: To compare prognosis of advanced epithelial ovarian cancer (AEOC) patients
      based on where the first surgical assessment was performed. PATIENTS AND METHODS:
      Retrospective analysis of primary AEOC patients was performed and three groups
      were formed based on where the decision of primary treatment was taken: Internal,
      if the decision was carried out at our Institution (PDS (Primary Debulking
      Surgery), I-IDS (Internal-Interval Debulking Surgery)) and Referred in case women
      were referred after neoadjuvant chemotherapy (NACT) from other Centers (R-IDS
      (Referred-Interval Debulking Surgery)). RESULTS: Among 573 AEOC, 279 (48.7%) were
      PDS and 294 (51.3%) IDS. In particular, 134 of 294 (45.6%) were R-IDS and 160
      (54.4%) were I-IDS. Median progression-free survival (PFS) was 26 months in PDS,
      14 months in I-IDS and 17 months in R-IDS. The difference was statistically
      significant (p<0.05) among all groups. CONCLUSION: IDS can represent a suitable
      approach only when the first complete debulking is not achievable in a tertiary
      referral hospital.

PMID- 25964592
TI  - Endoscopic radiofrequency ablation in elderly patients with hepatocellular
      carcinoma.
AB  - BACKGROUND: The number of elderly patients with hepatocellular carcinoma (HCC)
      has increased in Japan. PATIENTS AND METHODS: A total of 280 patients with HCC
      treated with endoscopic radiofrequency ablation (ERFA) were enrolled in the
      present study. The patients were divided into two groups, an elderly group (>= 70
      years) and a non-elderly group (<70 years) and their clinical and survival data
      were compared. RESULTS: The cumulative overall survival rates in the elderly and
      non-elderly groups were equivalent: 73% and 70% at three years and 57% and 52% at
      five years, respectively (p=0.900). The disease-free survival rates were 21% and
      23% at three years and 17% and 14% at five years, respectively (p=0.628). No
      significant effects were observed between the two groups due to any of the
      covariates in the survival analysis (all p-values for interaction >= 0.19). The
      complication rates were also comparable: 5.1% in the elderly group and 8.6% in
      the non-elderly group. CONCLUSION: ERFA is safe and provides excellent
      therapeutic effects in elderly as well as non-elderly patients with HCC.

PMID- 25964593
TI  - Single-phase Whole-body 64-MDCT Split-bolus Protocol for Pediatric Oncology:
      Diagnostic Efficacy and Dose Radiation.
AB  - PURPOSE: To evaluate the image quality and the diagnostic efficacy by single
      phase whole-body 64-slice multidetector CT (MDCT) for pediatric oncology.
      PATIENTS AND METHODS: Chest-abdomen-pelvis CT examinations with single-phase
      split-bolus technique were evaluated for T: detection and delineation of primary
      tumor (assessment of the extent of the lesion to neighboring tissues), N:
      regional lymph nodes and M: distant metastasis. Quality scores (5-point scale)
      were assessed by two radiologists on parenchymal and vascular enhancement.
      RESULTS: Accurate TNM staging in term of detection and delineation of primary
      tumor, regional lymph nodes and distant metastasis was obtained in all cases. On
      the image quality and severity artifact, the Kappa value for the interobserver
      agreement measure obtained from the analysis was 0.754, (p<0.001), characterizing
      a very good agreement between observers. CONCLUSION: Single-pass total body CT
      split-bolus technique reached the highest overall image quality and an accurate
      TNM staging in pediatric patients with cancer.

PMID- 25964594
TI  - Hypofractionated Dose Escalated 3D Conformal Radiotherapy for Prostate Cancer:
      Outcomes from a Mono-Institutional Phase II Study.
AB  - BACKGROUND/AIM: Based on a radiobiological assumption of a low alpha/beta
      (alpha/beta) ratio for prostate cancer, hypofractionated radiotherapy has
      increasingly gained traction in the clinical practice and recent guidelines have
      confirmed the non-inferiority of this approach. Nevertheless, the largest studies
      that have used hypofractionation so far, employed image-guided radiation
      therapy/intensity modulated radiation therapy (IGRT/IMRT) facilities that might
      have overcome the radiobiological advantages, which remain to be fully confirmed.
      The aim of this trial was to evaluate the feasibility of a hypofractionated
      schedule delivered with 3D-Conformal Radiotherapy to prostate and seminal
      vesicles in combination with hormonal therapy. PATIENTS AND METHODS: The study
      included 97 consecutive patients with localized prostate cancer (PCa),
      irrespective of risk class, treated with a schedule of 62 Gy in 20 fractions over
      5 weeks (4 fractions of 3.1 Gy each per week). According to National
      Comprehensive Cancer Network (NCCN) prognostic classification, patients were
      divided into a favourable group (19%), intermediate group (41%) and unfavourable
      group (40%). Early and late toxicities were scored using the radiation toxicity
      grading/European Organisation for Research and Treatment of Cancer (RTOG/EORTC)
      criteria. Additionally, the international prostate symptom index (IPSS) for
      benign prostate hypertrophy was used to evaluate obstructive urinary symptoms.
      Biochemical outcome was reported according to the Phoenix definition for
      biochemical failure. Hormonal therapy (HT) was administrated in 92% of patients.
      RESULTS: After a median follow-up of 39 months (range=25-52), maximum >=G2 late
      genitourinary (GU) and gastrointestinal (GI) toxicities occurred in 8% and 11%
      patients, respectively. The corresponding figures for acute toxicities were 24%
      and 15%. Patients with higher IPSS score before enrolment had significantly worse
      urinary function after treatment. Only 2% of patients died from PCa. Biochemical
      non-evidence of disease (bNED) was 83% for all patients. CONCLUSION: Our study
      confirms that 3D conformal radiotherapy (3DCRT) remains a safe and effective
      method to deliver a dose-escalated hypofractionated regimen for PCa patients in
      all risk classes with acceptable toxicity rates and optimal biochemical control.

PMID- 25964595
TI  - Radiosurgery or Fractionated Stereotactic Radiotherapy plus Whole-brain
      Radioherapy in Brain Oligometastases: A Long-term Analysis.
AB  - AIM: To analyze the outcome of patients with brain oligometastases treated by
      radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) after whole
      brain radiotherapy (WBRT). PATIENTS AND METHODS: Overall survival (OS) and local
      control (LC) were evaluated in patients (patients) with 1-2 brain metastases.
      RESULTS: Forty-seven patients were selected. They were submitted to WBRT (median
      dose=3,750 cGy) followed by SRS (17 patients; median dose=1,500 cGy) or FSRT (30
      patients; median dose=2,000 cGy). Median follow-up was 102 months (range=17-151);
      the median survival was 22 months for the SRS group and 16 months for the FSRT
      group. One-year and 5-year survival was 56% and 16%, respectively, in SRT and
      62.1% and 3%, respectively, in FSRT. Neither treatment proved to significantly
      impact OS (p=0.4). The 1-year LC rates were 80% and 61.1% in the two groups,
      respectively (p=0.15). CONCLUSION: SRS or FSRT after WBRT could offer the same
      outcomes in patients with brain oligometasteses. Further investigation is
      warranted to confirm these data and define the optimal stereotactic modality.

PMID- 25964596
TI  - Predictors of intrahepatic multiple recurrences after curative hepatectomy for
      hepatocellular carcinoma.
AB  - BACKGROUND/AIM: Survival of patients with multiple recurrences (MR) of
      hepatocellular carcinoma (HCC) is very poor as recurrent tumors are usually
      aggressive and not amenable to curative resection. The present study aimed to
      investigate retrospectively predictors of intrahepatic MR of HCC after
      hepatectomy. PATIENTS AND METHODS: We reviewed 416 patients who underwent
      hepatectomy and developed intrahepatic recurrence during the follow-up period.
      According to the recurrence pattern, the patients were divided into two groups:
      83 who had four or more recurrent lesions in the remnant liver were defined as
      the MR group and the others who constituted the control group. RESULTS:
      Multivariate analysis showed that micro-intrahepatic metastasis, alpha
      fetoprotein and tumor size were independent risk factors for MR after
      hepatectomy. The combination of these three independent factors was significantly
      associated with MR. The recurrence rates within 1 year after hepatectomy of MR
      and control groups were 53.0% and 27.6%, respectively (p=0.0001). The 5-year
      overall survival rate of the MR group was 39%, which was significantly less than
      that of the control group (68%, p<0.0001). CONCLUSIONS: MR of HCC was associated
      with an earlier recurrence and poorer survival after hepatectomy. The combination
      of three independent factors for MR might help predict MR occurrence during the
      follow-up period.

PMID- 25964597
TI  - No Significant Correlation of Clinical Outcomes Between First- and Second-line
      Tyrosine Kinase Inhibitors in Patients with Metastatic Renal Cell Carcinoma.
AB  - AIM: To identify patients with metastatic renal cell carcinoma (mRCC) who
      received tyrosine kinase inhibitors (TKIs) in both first- and second-line
      settings in order to investigate the association of oncological outcomes between
      the two lines of therapy. Patients with Methods: The study included 76
      consecutive patients with mRCC treated with second-line TKI therapy after the
      failure of first-line TKI therapy. The association of oncological outcomes
      between first- and second-line therapies was analyzed in these 76 patients.
      RESULTS: In this series, the objective response rates (ORRs) to first- and second
      line TKI therapies were 10.5% and 25.0%, respectively. The ORR to second-line TKI
      therapy was not significantly different among patients achieving a complete or
      partial response, stable disease and progressive disease to first-line TKI
      therapy (37.5%, 21.6% and 29.4%, respectively; p=0.34). The median durations of
      progression-free survival (PFS) with first- and second-line TKI therapies were
      7.9 and 8.1 months, respectively, and there was no significant correlation
      between them (p=0.78). Out of the examined factors, the pre-treatment C-reactive
      protein level, number of metastatic sites and Memorial Sloan-Kettering Cancer
      Center risk classification model, but not the response to first-line TKI therapy,
      were independently associated with PFS on second-line TKI therapy, based on
      multivariate analysis. CONCLUSION: The clinical response to second-line TKI
      therapy is not dependent on that to first-line TKI therapy in patients with mRCC;
      therefore, it may not be necessary to switch to an alternative agent with a
      mechanism different from TKIs as second-line therapy, even if patients do not
      respond to first-line TKI therapy.

PMID- 25964598
TI  - The Role of PCA 3 as a Prognostic Factor in Patients with Castration-resistant
      Prostate Cancer (CRPC) Treated with Docetaxel.
AB  - AIM: To investigate potential fluctuations in prostate cancer antigen 3 (PCA 3)
      scores in castration-resistant prostate cancer (CRPC) patients treated with
      docetaxel and investigate the assay as a potential prognostic factor. PATIENTS
      AND METHODS: This was a prospective observational cohort study. Inclusion
      criteria included patients on hormonal treatment who were recently diagnosed with
      CRPC. Exclusion criteria included patients previously having radical treatment
      (surgery or radiotherapy) and patients who have completed the first cycle of
      chemotherapy. All urine samples were collected and analyzed using the Progensa(r)
      assay. Samples were collected before starting chemotherapy and at 12 months. A
      prospective database was created including routine blood tests, prostate staging
      and prostate-specific antigen (PSA) levels throughout the study period. The
      effects of chemotherapy were also recorded. RESULTS: Between January 2010 and
      February 2013, 12 patients were included in the study out of an initial cohort of
      23 patients with CRPC. Mean follow-up was 14.8 months. Mean age at CRPC diagnosis
      was 73.8 years (+/-3.6 SD). Mean Gleason score was 8, with PSA 84.23 ng/ml (+/
      158 SD). Mean duration of androgen deprivation treatment (ADT) was 45.16 months
      (+/-34.9 SD). Mean time to castrate-resistant state was 46.58 months (+/-35.3
      SD). All twelve (n=12, 100%) patients had non-assessable PCA 3 scores at baseline
      and at 12 months follow-up. As a direct consequence, statistical analysis was not
      performed as the anticipated change in PCA 3 scores was not identified and
      correlation between measurable differences was not possible. All patients
      tolerated chemotherapy and completed the scheduled cycles with no serious adverse
      effects. CONCLUSION: To our knowledge, this is the first prospective study to
      demonstrate lack of expression of PCA3 in CRPC, with the result apparently not
      influenced by chemotherapy. There appears to be a strong association between
      hormonal treatment and lack of PCA 3 expression. It is still unknown whether
      disease progression per se affects PCA 3 scores. The gradual reduction and
      eventual complete non-expression of PCA 3 with ongoing treatment and disease
      progression provide an insight towards molecular pathways that may be connected
      to castration-resistant state.

PMID- 25964599
TI  - Mutations in the Spliceosomal Machinery Genes SRSF2, U2AF1, and ZRSR2 and
      Response to Decitabine in Myelodysplastic Syndrome.
AB  - BACKGROUND: Hypomethylating agents, such as azacitidine and decitabine, now
      constitute one of the mainstays of myelodysplastic syndrome (MDS) treatment. In
      recent years, novel recurrent mutations in multiple genes encoding RNA
      spliceosomal machinery (SRSF2, U2AF1, ZRSR2, SF3B1) were revealed. However, the
      clinical impact of these mutations on the outcomes of treatment of MDS patients
      with hypomethylating agents has not been described. PATIENTS AND METHODS: A total
      of 58 de novo MDS patients were included in the study who had received first-line
      decitabine treatment. Polymerase chain reaction (PCR) followed by direct
      sequencing analyses was performed for the spliceosomal machinery genes including
      SRSF2, U2AF1 and ZRSR2. RESULTS: In the present analysis of 58 Korean MDS
      patients, mutations in the splicing machinery genes SRSF2, U2AF1 and ZRSR2 were
      detected in 5 (8.6%), 10 (17.2%) and 6 (10.3%) patients, respectively, and the
      incidence of SRSF2 mutation was lower than those of previous series. The overall
      response rates (ORRs) including complete remission (CR), partial response (PR),
      and marrow CR (mCR) were 42.9% in the spliceosome wild-type (WT) group and 46.7%
      in the spliceosome-mutated group (p>0.999). The median OS was 22.0 months in the
      spliceosome-WT group and 15.9 months in the spliceosome-mutated group (p=0.267)
      CONCLUSION: This study firstly reports the impact of mutations of the
      spliceosomal machinery genes on the outcomes of decitabine treatment in MDS. The
      mutational status of the SRSF2, U2AF1 and ZRSR2 did not affect the response rate
      or survival in MDS patients who had received first-line decitabine treatment.
      Further studies are needed to confirm the prognostic relevance of spliceosome
      mutations to the clinical outcomes of treatment with hypomethylating agents.

PMID- 25964600
TI  - Population-based Analysis of the Clinical Features of Primary Small Cell
      Carcinoma of the Ovary.
AB  - BACKGROUND: Primary small cell carcinoma of the ovary (SCCO) is rare, making
      prognosis and outcomes largely undefined. PATIENTS AND METHODS: Using case
      listing session of SEER 18 (1973-2010), we examined outcomes for patients with
      SCCO. Analyses were conducted with SEER(*)Stat 8.1.2, Microsoft Excel 2007 and
      GraphPad Prism 6. Comparisons were made using the Chi-square test and log-rank
      test (Mantel-Cox) and all p-values were 2-sided. RESULTS: One hundred and eighty
      one patients with SCCO with staging information were identified with a median age
      of 37 (range=10-91). Twenty-nine patients (15%) had localized, 19 (11%) regional
      and 133 (74%) distant disease at presentation. All patients with localized and
      95% of patients with regional disease had surgery. The extent of surgery did not
      influence outcomes. Median overall survival (OS) varied by stage (67 months vs.
      12 months vs. 9 months, p<0.001). Radiation was rarely used in localized (1
      patient) or regional disease (3 patients). For comparison, 81,933 cases of SCLC
      were identified from the same database with a median age of 68; 8% of small cell
      lung cancer (SCLC) patients had localized, 29% regional and 63% distant disease.
      Outcomes were superior for patients with SCCO with localized disease (67 months
      vs. 16 months, p<0.001) but there was no clinically meaningful difference in
      patients with regional (12 months vs. 13 months, p=0.675) or distant disease (9
      months vs. 7 months, p<0.001). CONCLUSION: SCCO presents at a younger age than
      SCLC but has a similar stage distribution. Patients with localized SCCO have a
      more favorable prognosis than patients with SCLC but patients with regional and
      distant disease have similar outcomes.

PMID- 25964601
TI  - Reduced Dose of Abiraterone Acetate with Concomitant Low-dose Prednisone in the
      Treatment of >= 85 Year-old Patients with Advanced Castrate-resistant Prostate
      Cancer.
AB  - AIM: The aim of the study was to evaluate the activity and safety of reduced-dose
      abiraterone acetate (AA) in >= 85 year-old patients with advanced castrate
      resistant prostate cancer (CRPC). PATIENTS AND METHODS: Patients received 750 mg
      oral AA as three 250-mg tablets once daily, with concomitant oral prednisone, 5
      mg daily. RESULTS: Twenty-six patients were enrolled; median age was 88 years
      (range=85-93). Prostate-specific antigen (PSA) response was observed in 18
      (69.2%) subjects, median time to PSA progression was 6.4 months (95% confidence
      interval (CI)=2.8-8.8) and median overall survival was 14.3 months (95% CI=7.2
      18.3). The treatment was well-tolerated and adverse events, related to
      mineralocorticoid excess, were of grade 1-2 in all patients. CONCLUSION: Reduced
      dose of AA combined with a very low dose of prednisone is effective and well
      tolerated in very elderly patients with advanced CRPC.

PMID- 25964602
TI  - A new strategy for metachronous primary lung cancer: stereotactic body radiation
      therapy with concurrent chemotherapy.
AB  - BACKGROUND/AIM: Patients with malignant lung cancer often develop a solitary
      pulmonary nodule after treatment of the initial cancer. In those cases, it is
      difficult to distinguish primary lung cancer (PLC) from lung metastasis.
      Therefore, both local therapy for a single lung lesions and systemic therapy for
      micrometastases are needed. This retrospective study aimed to evaluate the safety
      and tolerability of concurrent stereotactic body radiation therapy (SBRT) and
      chemotherapy in patients with metachronous PLC. PATIENTS AND METHODS: We reviewed
      the records of 10 patients with metachronous PLC treated with SBRT and concurrent
      chemotherapy with curative intent from 2007 to 2013. The delivered radiation dose
      was 48 Gy in four fractions. RESULTS: All patients received SBRT with concurrent
      chemotherapy on schedule. Complete response rate was 90%. Safety profile of this
      treatment was compatible with that of traditional chemoradiotherapy. CONCLUSION:
      Our study showed good feasibility and safety for SBRT with concurrent
      chemoradiotherapy.

PMID- 25964603
TI  - Errata.

PMID- 25964628
TI  - A Multicenter, Single-Blind Randomized, Controlled Study of a Volumizing
      Hyaluronic Acid Filler for Midface Volume Deficit: Patient-Reported Outcomes at 2
      Years.
AB  - BACKGROUND: Juvederm Voluma XC is a volumizing hyaluronic acid filler used for
      correction of age-related midface volume deficit (MVD). OBJECTIVES: The
      effectiveness of Juvederm Voluma XC was examined from the patient perspective.
      METHODS: Patients with moderate to severe age-related MVD (N = 235) received
      Juvederm Voluma XC. At quarterly follow-up visits for 2 years, patients rated
      treatment outcomes on the Global Aesthetic Improvement Scale (GAIS), overall
      satisfaction with facial appearance, satisfaction with midfacial regions,
      achievement of treatment goal, Look and Feel of the Midface (LAFM), and Self
      Perception of Age (SPA). Patients recorded treatment-site responses in 30-day
      diaries. RESULTS: At 6 months and 2 years after treatment, 92.8% and 79.0% of
      patients, respectively, rated their cheek volume as improved/much improved on the
      GAIS. Improvement in satisfaction with facial appearance was noted by 89.8% of
      patients at 6 months and 75.8% at 2 years. Increased satisfaction with outer and
      lower cheek areas and cheek-bone projection and clinically significant
      improvements in LAFM were noted through month 24. Treatment goals were achieved
      by 67.8% of patients at 6 months and 49.0% at 2 years. Patients reported looking,
      on average, 5 years younger at 6 months and 3 years younger at 2 years. The most
      common treatment site responses were tenderness, swelling, firmness, and
      lumps/bumps; most were mild to moderate in severity and lasted <=2 weeks.
      CONCLUSIONS: Juvederm Voluma XC for age-related MVD is effective and well
      tolerated from the patient perspective, with results lasting up to 2 years. LEVEL
      OF EVIDENCE: 4 Therapeutic.

PMID- 25964629
TI  - Treatment of Hyaluronic Acid Filler-Induced Impending Necrosis With
      Hyaluronidase: Consensus Recommendations.
AB  - Injection-induced necrosis is a rare but dreaded consequence of soft tissue
      augmentation with filler agents. It usually occurs as a result of injection of
      filler directly into an artery, but can also result from compression or injury.
      We provide recommendations on the use of hyaluronidase when vascular compromise
      is suspected. Consensus recommendations were developed by thorough discussion and
      debate amongst the authors at a roundtable meeting on Wednesday June 18, 2014 in
      Las Vegas, NV as well as significant ongoing written and verbal communications
      amongst the authors in the months prior to journal submission. All authors are
      experienced tertiary care providers. A prompt diagnosis and immediate treatment
      with high doses of hyaluronidase (at least 200 U) are critically important. It is
      not felt necessary to do a skin test in cases of impending necrosis. Some experts
      recommend dilution with saline to increase dispersion or lidocaine to aid
      vasodilation. Additional hyaluronidase should be injected if improvement is not
      seen within 60 minutes. A warm compress also aids vasodilation, and massage has
      been shown to help. Some experts advocate the use of nitroglycerin paste,
      although this area is controversial. Introducing an oral aspirin regimen should
      help prevent further clot formation due to vascular compromise. In our
      experience, patients who are diagnosed promptly and treated within 24 hours will
      usually have the best outcomes. 

PMID- 25964630
TI  - PsyGeNET: a knowledge platform on psychiatric disorders and their genes.
AB  - PsyGeNET (Psychiatric disorders and Genes association NETwork) is a knowledge
      platform for the exploratory analysis of psychiatric diseases and their
      associated genes. PsyGeNET is composed of a database and a web interface
      supporting data search, visualization, filtering and sharing. PsyGeNET integrates
      information from DisGeNET and data extracted from the literature by text mining,
      which has been curated by domain experts. It currently contains 2642 associations
      between 1271 genes and 37 psychiatric disease concepts. In its first release,
      PsyGeNET is focused on three psychiatric disorders: major depression, alcohol and
      cocaine use disorders. PsyGeNET represents a comprehensive, open access resource
      for the analysis of the molecular mechanisms underpinning psychiatric disorders
      and their comorbidities. AVAILABILITY AND IMPLEMENTATION: The PysGeNET platform
      is freely available at http://www.psygenet.org/. The PsyGeNET database is made
      available under the Open Database License
      (http://opendatacommons.org/licenses/odbl/1.0/). CONTACT: lfurlong@imim.es
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 25964631
TI  - GOplot: an R package for visually combining expression data with functional
      analysis.
AB  - Despite the plethora of methods available for the functional analysis of omics
      data, obtaining comprehensive-yet detailed understanding of the results remains
      challenging. This is mainly due to the lack of publicly available tools for the
      visualization of this type of information. Here we present an R package called
      GOplot, based on ggplot2, for enhanced graphical representation. Our package
      takes the output of any general enrichment analysis and generates plots at
      different levels of detail: from a general overview to identify the most enriched
      categories (bar plot, bubble plot) to a more detailed view displaying different
      types of information for molecules in a given set of categories (circle plot,
      chord plot, cluster plot). The package provides a deeper insight into omics data
      and allows scientists to generate insightful plots with only a few lines of code
      to easily communicate the findings. AVAILABILITY AND IMPLEMENTATION: The R
      package GOplot is available via CRAN-The Comprehensive R Archive Network:
      http://cran.r-project.org/web/packages/GOplot. The shiny web application of the
      Venn diagram can be found at: https://wwalter.shinyapps.io/Venn/. A detailed
      manual of the package with sample figures can be found at
      https://wencke.github.io/ CONTACT: fscabo@cnic.es or mricote@cnic.es.

PMID- 25964632
TI  - Controversies in medical aid to developing countries: balancing help and harm.

PMID- 25964633
TI  - Reducing costs by changing behavior-really?

PMID- 25964634
TI  - Defining borderline resectable pancreatic cancer: emerging consensus for an old
      challenge.

PMID- 25964636
TI  - Sorafenib in Relapsed AML With FMS-Like Receptor Tyrosine Kinase-3 Internal
      Tandem Duplication Mutation.
AB  - Old age (<=65 years), relapsed or refractory disease, and the presence of FMS
      like receptor tyrosine kinase-3 (FLT3) internal tandem duplication (ITD) mutation
      are poor prognostic factors in acute myeloid leukemia (AML). FLT3 inhibitors such
      as sorafenib have been shown to have a potential role in treating relapsed or
      refractory AML with FLT3 mutations. In the present report, the use of sorafenib
      in combination with cytarabine and idarubicin resulted in disease control for 7
      months in an older patient with relapsed FLT3-positive AML. This case report and
      the existing literature indicate that sorafenib has disease activity against
      relapsed AML with the FLT3-ITD mutation in older patients. Larger multicenter
      studies should be conducted to confirm these findings, which have the potential
      to improve outcomes in this high-risk AML subgroup. 

PMID- 25964639
TI  - Omission of adjuvant therapy after gastric cancer resection: development of a
      validated risk model.
AB  - NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Gastric
      Cancer recommend adjuvant chemotherapy with or without radiotherapy following
      after resection of gastric adenocarcinoma (GA) for patients who have not received
      neoadjuvant therapy. Despite frequent noncompliance with NCCN Guidelines
      nationally, risk factors underlying adjuvant therapy omission (ATom) have not
      been well characterized. We developed an internally validated preoperative
      instrument stratifying patients by incremental risk of ATom. The National Cancer
      Data Base was queried for patients with stage IB-III GA undergoing gastrectomy;
      those receiving neoadjuvant therapy were excluded. Multivariable models
      identified factors associated with ATom between 2006 and 2011. Internal
      validation was performed using bootstrap analysis; model discrimination and
      calibration were assessed using k-fold cross-validation and Hosmer-Lemeshow
      procedures, respectively. Using weighted beta-coefficients, a simplified Omission
      Risk Score (ORS) was created to stratify ATom risk. The impact of ATom on overall
      survival (OS) was examined in ORS risk-stratified cohorts. In 4,728 patients
      (median age, 70 years; 64.8% male), 53.7% had ATom. The bootstrap-validated model
      identified advancing age, comorbidity, underinsured/uninsured status, proximal
      tumor location, and clinical T1/2 and N0 tumors as independent ATom predictors,
      demonstrating good discrimination. The simplified ORS, stratifying patients into
      low-, moderate-, and high-risk categories, predicted incremental risk of ATom
      (30% vs 53% vs 80%, respectively) and progressive delay to adjuvant therapy
      initiation (median time, 51 vs 55 vs 61 days, respectively). Patients at
      moderate/high-risk of ATom demonstrated worsening risk-adjusted mortality
      compared with low-risk patients (median OS, 26.4 vs 29.2 months). This ORS may
      aid in rational selection of multimodality treatment sequence in GA. 

PMID- 25964638
TI  - Use of Postprostatectomy Radiation Therapy at an NCI-Designated Comprehensive
      Cancer Center.
AB  - PURPOSE: Characterize use of postprostatectomy radiation (PPRT) for patients with
      prostate cancer at an NCI-designated comprehensive cancer center. METHODS: We
      queried our prospective prostate cancer database for patients treated with 60 to
      68 Gy of radiation therapy (RT) to the prostate bed after prostatectomy from 2003
      to 2011. Prostatectomy cases were obtained from billing records. Patients with an
      intact prostate treated with definitive RT served as a control for the change in
      volume of patients with prostate cancer treated in the department. Chi-square
      analysis assessed differences between adjuvant and salvage RT cohorts. Spearman
      correlation assessed yearly trends in prostate-specific antigen (PSA) level at
      the time of referral for RT. Linear regression models tested trends for number of
      PPRT cases, prostatectomies, and patients with intact prostate receiving
      radiation across years. RESULTS: PPRT was used to treat 475 men at Fox Chase
      Cancer Center from 2003 to 2011 (83 adjuvant and 392 salvage). Over time, an
      increased proportion of patients receiving RT to the prostate were treated with
      PPRT. No increase was seen in the proportion of patients treated with adjuvant RT
      compared with salvage RT (P=.5). Patients receiving adjuvant RT were younger, had
      higher pathologic Gleason score, pathologic T stage, and rates of positive
      margins than those receiving salvage RT. Pre-RT PSA values were inversely
      correlated with year (P=.005). The number of patients referred for salvage RT
      with a PSA of 0.5 ng/mL or less increased significantly from 7.9% in 2003 to
      26.6% in 2011 (P=.002). CONCLUSIONS: A larger proportion of patients treated with
      RT for localized prostate cancer are now receiving PPRT. No increase was seen in
      the proportion of patients treated with adjuvant RT. Over time, patients with
      lower PSAs were referred for salvage RT.

PMID- 25964637
TI  - Non-Small Cell Lung Cancer, Version 6.2015.
AB  - These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN
      Guidelines for Non-Small Cell Lung Cancer (NSCLC). Appropriate targeted therapy
      is very effective in patients with advanced NSCLC who have specific genetic
      alterations. Therefore, it is important to test tumor tissue from patients with
      advanced NSCLC to determine whether they have genetic alterations that make them
      candidates for specific targeted therapies. These NCCN Guidelines Insights
      describe the different testing methods currently available for determining
      whether patients have genetic alterations in the 2 most commonly actionable
      genetic alterations, notably anaplastic lymphoma kinase (ALK) gene rearrangements
      and sensitizing epidermal growth factor receptor (EGFR) mutations. 

PMID- 25964640
TI  - Diagnostic delays are common among patients with hepatocellular carcinoma.
AB  - BACKGROUND: Most patients with hepatocellular carcinoma (HCC) present at advanced
      stages. The prevalence and clinical impact of delays during diagnostic evaluation
      among patients with HCC is unclear. PURPOSE: To identify and characterize factors
      associated with diagnostic delays among patients with HCC. METHODS: Records were
      reviewed for consecutive patients with cirrhosis and HCC at a large urban
      hospital between January 2005 and July 2012. Time from presentation to diagnosis
      was determined using Kaplan-Meier analysis. Diagnostic delay was defined as time
      to diagnosis exceeding 3 months, and multivariate logistic regression was used to
      identify correlates of diagnostic delays. RESULTS: Among 457 patients with HCC,
      226 (49.5%) were diagnosed as outpatients. Among these, median time-to-diagnosis
      was 2.2 months, with 87 patients (38.5%) experiencing a diagnostic delay.
      Diagnostic delays were positively associated with the presence of hepatic
      encephalopathy (odds ratio [OR], 2.29; 95% CI, 1.03-5.07) and negatively
      associated with presentation after implementation of the electronic medical
      records (EMR) (OR, 0.28; 95% CI, 0.15-0.52) and presentation with an abnormal
      ultrasound (OR, 0.36; 95% CI, 0.19-0.67) on multivariate analysis. Higher rates
      of diagnostic delays were observed among those with hepatic encephalopathy (56%
      vs 35%), whereas lower rates were seen in those who presented after EMR
      implementation (26% vs 60%) and those who presented with an abnormal ultrasound
      with or without an elevated alpha fetoprotein level (27% vs 50%). Among 49
      patients with mass-forming HCC and diagnostic delay, 18% had interval tumor
      growth of 2 cm or greater. CONCLUSIONS: Nearly 20% of patients with HCC wait more
      than 3 months from presentation to diagnosis, which can contribute to interval
      tumor growth.

PMID- 25964642
TI  - Biologic agents in the management of Hodgkin lymphoma.
AB  - The advent of biologic approaches for the treatment of solid tumors and
      hematologic malignancies has been a major accomplishment in oncology and a
      rapidly growing field of clinical and translational research in cancer
      therapeutics. Classical Hodgkin lymphoma (HL) is no exception. Although the
      investigation of biologic therapies in HL started decades ago, it has only
      recently flourished, largely because of the development of new monoclonal
      antibody drug conjugates and checkpoint inhibitors. Biologic therapies represent
      a potent treatment option that have produced durable remissions even in patients
      who have had multiple relapses or with refractory disease. This article reviews 8
      major classes of biologic approaches that have been investigated in HL:
      monoclonal antibodies, immunotoxins, antibody-drug conjugates,
      radioimmunotherapy, adoptive immunotherapy, immunomodulators, chimeric antigen
      receptor T cells, and checkpoint inhibitors. An armamentarium of biologic
      therapies for HL that are well tolerated and potentially more effective is
      expected to be available in the near future. 

PMID- 25964643
TI  - Contemporary radiation therapy in combined modality therapy for Hodgkin lymphoma.
AB  - The advent of effective combination chemotherapy markedly changed the management
      of Hodgkin lymphoma, establishing combined modality therapy as the standard of
      care for most patients with this disease. In response, significant interest has
      been shown in refining the delivery of radiation in the combined modality setting
      such that toxicity is minimized while still preserving disease control. An
      understanding of the way in which radiation treatment fields, prescription dose,
      and advanced technology have evolved to accomplish these goals is critical.
      Moreover, fluency in the clinical literature exploring contemporary questions,
      such as the omission of radiation and response-based treatment, is equally
      important. Knowledge of these topics will yield both an appreciation of the value
      of radiation in the combined modality setting and the ability to better customize
      treatment regimens to individual patients. 

PMID- 25964644
TI  - The need for United States-based guidelines for myeloproliferative neoplasms.

PMID- 25964641
TI  - Hodgkin lymphoma, version 2.2015.
AB  - Hodgkin lymphoma (HL) is an uncommon malignancy involving lymph nodes and the
      lymphatic system. Classical Hodgkin lymphoma (CHL) and nodular lymphocyte
      predominant Hodgkin lymphoma are the 2 main types of HL. CHL accounts for most HL
      diagnosed in the Western countries. Chemotherapy or combined modality therapy,
      followed by restaging with PET/CT to assess treatment response using the
      Deauville criteria (5-point scale), is the standard initial treatment for
      patients with newly diagnosed CHL. Brentuximab vedotin, a CD30-directed antibody
      drug conjugate, has produced encouraging results in the treatment of relapsed or
      refractory disease. The potential long-term effects of treatment remain an
      important consideration, and long-term follow-up is essential after completion of
      treatment. 

PMID- 25964647
TI  - Response to: The imaging spectrum of pulmonary tuberculosis: a critical
      appraisal. Acta Radiol 2015;56:NP1-NP2.

PMID- 25964648
TI  - Adjusting Bowel Regimens When Prescribing Opioids in Women Receiving Palliative
      Care in the Acute Care Setting.
AB  - In palliative medicine, constipation is the third most common symptom after pain
      and anorexia, causing some patients to discontinue opioid therapy. Women
      experience higher incidence of constipation than men. The prevalence of
      infrequent bowel movements (<3 times/wk) and adherence to an established bowel
      regimen among women receiving opioids were studied. Referral to the palliative
      care team decreased the prevalence of infrequent bowel movements from 72% to 45%,
      and algorithm adherence increased from 38% to 78%. Education of oncology nurses
      decreased the prevalence of infrequent bowel movements among patients with cancer
      from 71% to 60%, and algorithm adherence increased from 0% to 10%. Patients
      benefit from stool softeners and stimulants when receiving opioids. 

PMID- 25964649
TI  - Comparing Direct Stenting With Conventional Stenting in Patients With Acute
      Coronary Syndromes: A Meta-Analysis of 12 Clinical Trials.
AB  - Our aim was to compare direct stenting (DS) with conventional stenting (CS) in
      patients with acute coronary syndrome (ACS). We searched PubMed, EMBASE, and ISI
      web of science for eligible studies. Primary end point was major adverse cardiac
      events (MACEs) in short term. Secondary end points were 1-year mortality and
      after-procedural no-reflow phenomenon. Twelve trials in 8998 patients were
      included. The odds ratios (ORs) were pooled using the Mantel-Haenszel fixed
      effect model. Short-term MACEs were significantly reduced in the DS arm in
      contrast to the CS (5.00% vs 8.08%, DS vs CS, respectively, OR [95% confidence
      interval] = 0.61 [0.46-0.80], P = .0004). One-year mortality and after-procedural
      no-reflow phenomenon were significantly lower in the DS group. No heterogeneity
      was observed through I(2) test (Phet = .81, .89, and .77 for each end point,
      respectively). This meta-analysis demonstrated that in selected patients with
      ACS, DS is not only safe and feasible but also reduces short-term and 1-year
      mortality as well as the occurrence of after-procedural no-reflow phenomenon. 

PMID- 25964651
TI  - Architectures of multisubunit complexes revealed by a visible immunoprecipitation
      assay using fluorescent fusion proteins.
AB  - In this study, we elucidated the architectures of two multisubunit complexes, the
      BBSome and exocyst, through a novel application of fluorescent fusion proteins.
      By processing lysates from cells co-expressing GFP and RFP fusion proteins for
      immunoprecipitation with anti-GFP nanobody, protein-protein interactions could be
      reproducibly visualized by directly observing the immunoprecipitates under a
      microscope, and evaluated using a microplate reader, without requiring
      immunoblotting. Using this 'visible' immunoprecipitation (VIP) assay, we mapped
      binary subunit interactions of the BBSome complex, and determined the hierarchies
      of up to four subunit interactions. We also demonstrated the assembly sequence of
      the BBSome around the centrosome, and showed that BBS18 (also known as BBIP1 and
      BBIP10) serves as a linker between BBS4 and BBS8 (also known as TTC8). We also
      applied the VIP assay to mapping subunit interactions of the exocyst tethering
      complex. By individually subtracting the eight exocyst subunits from multisubunit
      interaction assays, we unequivocally demonstrated one-to-many subunit
      interactions (Exo70 with Sec10+Sec15, and Exo84 with Sec10+Sec15+Exo70). The
      simple, versatile VIP assay described here will pave the way to understanding the
      architectures and functions of multisubunit complexes involved in a variety of
      cellular processes. 

PMID- 25964650
TI  - Rab32 is essential for maintaining functional acidocalcisomes, and for growth and
      infectivity of Trypanosoma cruzi.
AB  - The contractile vacuole complex (CVC) of Trypanosoma cruzi, the etiologic agent
      of Chagas disease, collects and expels excess water as a mechanism of regulatory
      volume decrease after hyposmotic stress; it also has a role in cell shrinking
      after hyperosmotic stress. Here, we report that, in addition to its role in
      osmoregulation, the CVC of T. cruzi has a role in the biogenesis of
      acidocalcisomes. Expression of dominant-negative mutants of the CVC-located small
      GTPase Rab32 (TcCLB.506289.80) results in lower numbers of less-electron-dense
      acidocalcisomes, lower content of polyphosphate, lower capacity for
      acidocalcisome acidification and Ca(2+) uptake that is driven by the vacuolar
      proton pyrophosphatase and the Ca(2+)-ATPase, respectively, as well as less
      infective parasites, revealing the role of this organelle in parasite
      infectivity. By using fluorescence, electron microscopy and electron tomography
      analyses, we provide further evidence of the active contact of acidocalcisomes
      with the CVC, indicating an active exchange of proteins between the two
      organelles. 

PMID- 25964652
TI  - The juxtamembrane region of synaptotagmin 1 interacts with dynamin 1 and
      regulates vesicle fission during compensatory endocytosis in endocrine cells.
AB  - Synaptotagmin 1 (Syt1) is a synaptic vesicle protein that is important for the
      kinetics of both exocytosis and endocytosis, and is thus a candidate molecule to
      link these two processes. Although the tandem Ca(2+)-binding C2 domains of Syt1
      have important roles in exocytosis and endocytosis, the function of the conserved
      juxtamembrane (jxm) linker region has yet to be determined. We now demonstrate
      that the jxm region of Syt1 interacts directly with the pleckstrin homology (PH)
      domain of the endocytic protein dynamin 1. By using cell-attached capacitance
      recordings with millisecond time resolution to monitor clathrin-mediated
      endocytosis of single vesicles in neuroendocrine chromaffin cells, we find that
      loss of this interaction prolongs the lifetime of the fission pore leading to
      defects in the dynamics of vesicle fission. These results indicate a previously
      undescribed interaction between two major regulatory proteins in the secretory
      vesicle cycle and that this interaction regulates endocytosis. 

PMID- 25964653
TI  - Sertraline-induced periorbital purpura: a case report.
AB  - OBJECTIVE: The incidence of mild to severe levels of spontaneous bleeding due to
      the usage of selective serotonin reuptake inhibitors (SSRIs) is relatively low.
      Although the exact mechanism is not known, it is thought that inhibition of the
      serotonin transporter together with a decrease in platelet serotonin could be
      responsible for the bleeding. Therefore, the use of SSRIs in conjunction with
      anti-aggregants may predispose to or exacerbate the risk of bleeding. In this
      case report, we describe a 44-year-old female patient with a diagnosis of anxiety
      disorder who spontaneously developed periorbital purpura during treatment with
      sertraline. CONCLUSION: Abnormal bleeding after treatment with an SSRI should be
      kept in mind, and alternative non-SSRI drugs of choice in such cases would be
      more appropriate. More extensive and comprehensive studies focusing on hemostasis
      and bleeding disorders are needed for SSRIs such as sertraline.

PMID- 25964654
TI  - Can findings from randomized controlled trials of social skills training in
      autism spectrum disorder be generalized? The neglected dimension of external
      validity.
AB  - Systematic reviews have traditionally focused on internal validity, while
      external validity often has been overlooked. In this study, we systematically
      reviewed determinants of external validity in the accumulated randomized
      controlled trials of social skills group interventions for children and
      adolescents with autism spectrum disorder. We extracted data clustered into six
      overarching themes: source population, included population, context, treatment
      provider, treatment intervention, and outcome. A total of 15 eligible randomized
      controlled trials were identified. The eligible population was typically limited
      to high-functioning school-aged children with autism spectrum disorder, and the
      included population was predominantly male and Caucasian. Scant information about
      the recruitment of participants was provided, and details about treatment
      providers and settings were sparse. It was not evident from the trials to what
      extent acquired social skills were enacted in everyday life and maintained over
      time. We conclude that the generalizability of the accumulated evidence is
      unclear and that the determinants of external validity are often inadequately
      reported. At this point, more effectiveness-oriented randomized controlled trials
      of equally high internal and external validity are needed. More attention to the
      determinants of external validity is warranted when this new generation of
      randomized controlled trials are planned and reported. We provide a tentative
      checklist for this purpose. 

PMID- 25964655
TI  - Characterizing the daily life, needs, and priorities of adults with autism
      spectrum disorder from Interactive Autism Network data.
AB  - Using online survey data from a large sample of adults with autism spectrum
      disorder and legal guardians, we first report outcomes across a variety of
      contexts for participants with a wide range of functioning, and second, summarize
      these stakeholders' priorities for future research. The sample included n = 255
      self-reporting adults with autism spectrum disorder aged 18-71 years (M = 38.5
      years, standard deviation = 13.1 years) and n = 143 adults with autism spectrum
      disorder aged 18-58 years (M = 25.0 years, standard deviation = 8.2 years) whose
      information was provided by legal guardians. Although the self-reporting
      subsample had much higher rates of employment, marriage/partnership, and
      independent living than are typically seen in autism spectrum disorder outcome
      studies, they remained underemployed and had strikingly high rates of comorbid
      disorders. Data on both descriptive outcomes and rated priorities converged
      across subsamples to indicate the need for more adult research on life skills,
      treatments, co-occurring conditions, and vocational and educational
      opportunities. Stakeholders also placed priority on improving public services,
      health care access, and above all, public acceptance of adults with autism
      spectrum disorder. Findings must be interpreted in light of the self-reporting
      subsample's significant proportion of females and of later-diagnosed individuals.
      This study underscores the need for lifespan research; initiatives will benefit
      from incorporating information from the unique perspectives of adults with autism
      spectrum disorder and their families. 

PMID- 25964656
TI  - DNA Methylation Patterns in Peripheral Blood of Pregnant Women With Group B
      Streptococcus Colonization.
AB  - The primary risk factor for neonatal Group B streptococcus (GBS) infection, which
      is the leading cause of infectious neonatal morbidity and mortality, is maternal
      colonization. However, no definitive maternal risk factors for GBS colonization
      have been identified and no systematic efforts have been made to prevent maternal
      colonization. The purpose of this exploratory secondary analysis was to evaluate
      genome-wide DNA methylation patterns in maternal peripheral blood early in
      pregnancy for association with GBS colonization status in the third trimester.
      Genome-wide DNA methylation was analyzed from 18 nulliparous GBS-positive and 
      negative women (n = 9/group) recruited for a previous study. No statistically
      significant differences in baseline characteristics or DNA methylation in
      peripheral blood were identified between GBS-positive and -negative women in
      early pregnancy. The results suggest that DNA methylation patterns in peripheral
      blood are not associated with risk for GBS colonization.

PMID- 25964657
TI  - ADME SARfari: comparative genomics of drug metabolizing systems.
AB  - MOTIVATION: ADME SARfari is a freely available web resource that enables
      comparative analyses of drug-disposition genes. It does so by integrating a
      number of publicly available data sources, which have subsequently been used to
      build data mining services, predictive tools and visualizations for drug
      metabolism researchers. The data include the interactions of small molecules with
      ADME (absorption, distribution, metabolism and excretion) proteins responsible
      for the metabolism and transport of molecules; available pharmacokinetic (PK)
      data; protein sequences of ADME-related molecular targets for pre-clinical model
      species and human; alignments of the orthologues including information on known
      SNPs (Single Nucleotide Polymorphism) and information on the tissue distribution
      of these proteins. In addition, in silico models have been developed, which
      enable users to predict which ADME relevant protein targets a novel compound is
      likely to interact with.

PMID- 25964658
TI  - The ArfGAP2/3 Glo3 and ergosterol collaborate in transport of a subset of
      cargoes.
AB  - Proteins reach the plasma membrane through the secretory pathway in which the
      trans Golgi network (TGN) acts as a sorting station. Transport from the TGN to
      the plasma membrane is maintained by a number of different pathways that act
      either directly or via the endosomal system. Here we show that a subset of
      cargoes depends on the ArfGAP2/3 Glo3 and ergosterol to maintain their proper
      localization at the plasma membrane. While interfering with neither ArfGAP2/3
      activity nor ergosterol biosynthesis individually significantly altered plasma
      membrane localization of the tryptophan transporter Tat2, the general amino acid
      permease Gap1 and the v-SNARE Snc1, in a Deltaglo3 Deltaerg3 strain those
      proteins accumulated in internal endosomal structures. Export from the TGN to the
      plasma membrane and recycling from early endosomes appeared unaffected as the
      chitin synthase Chs3 that travels along these routes was localized normally. Our
      data indicate that a subset of proteins can reach the plasma membrane efficiently
      but after endocytosis becomes trapped in endosomal structures. Our study supports
      a role for ArfGAP2/3 in recycling from endosomes and in transport to the
      vacuole/lysosome. 

PMID- 25964659
TI  - The influence of motion quality on responses towards video playback stimuli.
AB  - Visual motion, a critical cue in communication, can be manipulated and studied
      using video playback methods. A primary concern for the video playback researcher
      is the degree to which objects presented on video appear natural to the non-human
      subject. Here we argue that the quality of motion cues on video, as determined by
      the video's image presentation rate (IPR), are of particular importance in
      determining a subject's social response behaviour. We present an experiment
      testing the effect of variations in IPR on pigeon (Columbia livia) response
      behaviour towards video images of courting opposite sex partners. Male and female
      pigeons were presented with three video playback stimuli, each containing a
      different social partner. Each stimulus was then modified to appear at one of
      three IPRs: 15, 30 or 60 progressive (p) frames per second. The results showed
      that courtship behaviour became significantly longer in duration as IPR
      increased. This finding implies that the IPR significantly affects the perceived
      quality of motion cues impacting social behaviour. In males we found that the
      duration of courtship also depended on the social partner viewed and that this
      effect interacted with the effects of IPR on behaviour. Specifically, the effect
      of social partner reached statistical significance only when the stimuli were
      displayed at 60 p, demonstrating the potential for erroneous results when
      insufficient IPRs are used. In addition to demonstrating the importance of IPR in
      video playback experiments, these findings help to highlight and describe the
      role of visual motion processing in communication behaviour. 

PMID- 25964660
TI  - The eyes of the deep diving hooded seal (Cystophora cristata) enhance sensitivity
      to ultraviolet light.
AB  - The mammalian visual range is approximately 400-700 nm, although recent evidence
      suggests varying ultraviolet (UV) extensions in diverse terrestrial species. UV
      sensitivity may have advantages in the dim, blue light shifted environment
      experienced by submerged marine mammals. It may also be advantageous when seals
      are on land as UV is reflected by snow and ice but absorbed by fur, enhancing
      visual contrast. Here we show that the pelagic hooded seal (Cystophora cristata)
      has a highly UV permissive cornea and lens. Seals like other carnivores have a
      tapetum lucidum (TL) reflecting light back through the retina increasing
      sensitivity. The TL in this seal is unusual being white and covering almost the
      entire retina unlike that in other carnivores. Spectral reflectance from its
      surface selectively increases the relative UV/blue components >10 times than
      other wavelengths. Retinal architecture is consistent with a high degree of
      convergence. Enhanced UV from a large TL surface with a high degree of retinal
      convergence will increase sensitivity at a cost to acuity. UV
      electrophysiological retina responses were only obtained to dim, rod mediated
      stimuli, with no evidence of cone input. As physiological measurements of
      threshold sensitivity are much higher than those for psychophysical detection,
      these seals are likely to be more UV sensitive than our results imply. Hence, UV
      reflections from the TL will afford increased sensitivity in dim oceanic
      environments. 

PMID- 25964661
TI  - The cuticle modulates ultraviolet reflectance of avian eggshells.
AB  - Avian eggshells are variedly coloured, yet only two pigments, biliverdin and
      protoporphyrin IX, are known to contribute to the dramatic diversity of their
      colours. By contrast, the contributions of structural or other chemical
      components of the eggshell are poorly understood. For example, unpigmented
      eggshells, which appear white to the human eye, vary in their ultraviolet (UV)
      reflectance, which may be detectable by birds. We investigated the proximate
      mechanisms for the variation in UV-reflectance of unpigmented bird eggshells
      using spectrophotometry, electron microscopy, chemical analyses, and experimental
      manipulations. We specifically tested how UV-reflectance is affected by the
      eggshell cuticle, the outermost layer of most avian eggshells. The chemical
      dissolution of the outer eggshell layers, including the cuticle, increased UV
      reflectance for only eggshells that contained a cuticle. Our findings demonstrate
      that the outer eggshell layers, including the cuticle, absorb UV-light, probably
      because they contain higher levels of organic components and other chemicals,
      such as calcium phosphates, compared to the predominantly calcite-based eggshell
      matrix. These data highlight the need to examine factors other than the known
      pigments in studies of avian eggshell colour. 

PMID- 25964662
TI  - Two-stage biomarker panel study and estimation allowing early termination for
      futility.
AB  - Technological advances have yielded a wealth of biomarkers that have the
      potential to detect chronic diseases such as cancer. However, most biomarkers
      considered for further validation turn out not to have strong enough performance
      to be used in clinical practice. Group sequential designs that allow early
      termination for futility may be cost-effective for biomarker studies based on
      biobanks of stored specimens. Previous studies proposed a group sequential design
      for the validation of a single biomarker. In this article, we adapt a 2-stage
      design to the setting where a panel of candidate biomarkers are under
      investigation. Conditional estimators of the clinical performance are proposed
      under an updated risk model that uses all accrued data, and can be computed
      through resampling procedures. Under a special case where a multivariate binormal
      distribution applies for biomarkers following a suitable transformation, these
      estimators have analytical forms, alleviating the computational burden while
      retaining statistical efficiency. Performance of the proposed 2-stage design and
      estimators are compared with a traditional fixed-sample design and an existing 2
      stage design that allows early termination but does not update the risk model
      with accrued information. Our proposed design and estimators show an ability to
      reduce sample size when the biomarker panel is not promising, while controlling
      rejection rate and gaining efficiency when the panel is promising. We apply the
      proposed methods to a biomarker panel development for the detection of high-grade
      prostate cancer in a study conducted within the National Cancer Institute's Early
      Detection Research Network. 

PMID- 25964663
TI  - Compound hierarchical correlated beta mixture with an application to cluster
      mouse transcription factor DNA binding data.
AB  - Modeling correlation structures is a challenge in bioinformatics, especially when
      dealing with high throughput genomic data. A compound hierarchical correlated
      beta mixture (CBM) with an exchangeable correlation structure is proposed to
      cluster genetic vectors into mixture components. The correlation coefficient,
      [Formula: see text], is homogenous within a mixture component and heterogeneous
      between mixture components. A random CBM with [Formula: see text] brings more
      flexibility in explaining correlation variations among genetic variables.
      Expectation-Maximization (EM) algorithm and Stochastic Expectation-Maximization
      (SEM) algorithm are used to estimate parameters of CBM. The number of mixture
      components can be determined using model selection criteria such as AIC, BIC and
      ICL-BIC. Extensive simulation studies were conducted to compare EM, SEM and model
      selection criteria. Simulation results suggest that CBM outperforms the
      traditional beta mixture model with lower estimation bias and higher
      classification accuracy. The proposed method is applied to cluster transcription
      factor-DNA binding probability in mouse genome data generated by Lahdesmaki and
      others (2008, Probabilistic inference of transcription factor binding from
      multiple data sources. PLoS One, 3: , e1820). The results reveal distinct
      clusters of transcription factors when binding to promoter regions of genes in
      JAK-STAT, MAPK and other two pathways. 

PMID- 25964664
TI  - Shape analysis of high-throughput transcriptomics experiment data.
AB  - The recent growth of high-throughput transcriptome technology has been paralleled
      by the development of statistical methodologies to analyze the data they produce.
      Some of these newly developed methods are based on the assumption that the data
      observed or a transformation of the data are relatively symmetric with light
      tails, usually summarized by assuming a Gaussian random component. It is indeed
      very difficult to assess this assumption for small sample sizes. In this article,
      we utilize L-moments statistics as the basis of exploratory data analysis, the
      assessment of distributional assumptions, and the hypothesis testing of high
      throughput transcriptomic data. In particular, we use L-moments ratios for
      assessing the shape (skewness and kurtosis) of high-throughput transcriptome
      data. Based on these statistics, we propose an algorithm for identifying genes
      with distributions that are markedly different from the majority in the data. In
      addition, we also illustrate the utility of this framework to characterize the
      robustness of distributional assumptions. We apply it to RNA-seq data and find
      that methods based on the simple [Formula: see text]-test for differential
      expression analysis using L-moments as weights are robust. 

PMID- 25964665
TI  - Strava: challenge yourself to greater heights in physical activity/cycling and
      running.

PMID- 25964667
TI  - Platelet geometry sensing spatially regulates alpha-granule secretion to enable
      matrix self-deposition.
AB  - Although the biology of platelet adhesion on subendothelial matrix after vascular
      injury is well characterized, how the matrix biophysical properties affect
      platelet physiology is unknown. Here we demonstrate that geometric orientation of
      the matrix itself regulates platelet alpha-granule secretion, a key component of
      platelet activation. Using protein microcontact printing, we show that platelets
      spread beyond the geometric constraints of fibrinogen or collagen micropatterns
      with <5-um features. Interestingly, alpha-granule exocytosis and deposition of
      the alpha-granule contents such as fibrinogen and fibronectin were primarily
      observed in those areas of platelet extension beyond the matrix protein
      micropatterns. This enables platelets to "self-deposit" additional matrix,
      provide more cellular membrane to extend spreading, and reinforce platelet
      platelet connections. Mechanistically, this phenomenon is mediated by actin
      polymerization, Rac1 activation, and alphaIIbbeta3 integrin redistribution and
      activation, and is attenuated in gray platelet syndrome platelets, which lack
      alpha-granules, and Wiskott-Aldrich syndrome platelets, which have cytoskeletal
      defects. Overall, these studies demonstrate how platelets transduce geometric
      cues of the underlying matrix geometry into intracellular signals to extend
      spreading, which endows platelets spatial flexibility when spreading onto small
      sites of exposed subendothelium. 

PMID- 25964670
TI  - Evidence is insufficient to recommend e-cigarettes for quitting, US committee
      concludes.

PMID- 25964668
TI  - Regulation of actin polymerization by tropomodulin-3 controls megakaryocyte actin
      organization and platelet biogenesis.
AB  - The actin cytoskeleton is important for platelet biogenesis. Tropomodulin-3
      (Tmod3), the only Tmod isoform detected in platelets and megakaryocytes (MKs),
      caps actin filament (F-actin) pointed ends and binds tropomyosins (TMs),
      regulating actin polymerization and stability. To determine the function of Tmod3
      in platelet biogenesis, we studied Tmod3(-/-) embryos, which are embryonic lethal
      by E18.5. Tmod3(-/-) embryos often show hemorrhaging at E14.5 with fewer and
      larger platelets, indicating impaired platelet biogenesis. MK numbers are
      moderately increased in Tmod3(-/-) fetal livers, with only a slight increase in
      the 8N population, suggesting that MK differentiation is not significantly
      affected. However, Tmod3(-/-) MKs fail to develop a normal demarcation membrane
      system (DMS), and cytoplasmic organelle distribution is abnormal. Moreover,
      cultured Tmod3(-/-) MKs exhibit impaired proplatelet formation with a wide range
      of proplatelet bud sizes, including abnormally large proplatelet buds containing
      incorrect numbers of von Willebrand factor-positive granules. Tmod3(-/-) MKs
      exhibit F-actin disturbances, and Tmod3(-/-) MKs spreading on collagen fail to
      polymerize F-actin into actomyosin contractile bundles. Tmod3 associates with TM4
      and the F-actin cytoskeleton in wild-type MKs, and confocal microscopy reveals
      that Tmod3, TM4, and F-actin partially colocalize near the membrane of
      proplatelet buds. In contrast, the abnormally large proplatelets from Tmod3(-/-)
      MKs show increased F-actin and redistribution of F-actin and TM4 from the cortex
      to the cytoplasm, but normal microtubule coil organization. We conclude that F
      actin capping by Tmod3 regulates F-actin organization in mouse fetal liver
      derived MKs, thereby controlling MK cytoplasmic morphogenesis, including DMS
      formation and organelle distribution, as well as proplatelet formation and
      sizing. 

PMID- 25964671
TI  - Piece of string can assess cardiovascular risk, study finds.

PMID- 25964669
TI  - How I treat hypereosinophilic syndromes.
AB  - Hypereosinophilic syndromes (HESs) are a group of rare disorders characterized by
      peripheral blood eosinophilia of 1.5 * 10(9)/L or higher and evidence of end
      organ manifestations attributable to the eosinophilia and not otherwise explained
      in the clinical setting. HESs are pleomorphic in clinical presentation and can be
      idiopathic or associated with a variety of underlying conditions, including
      allergic, rheumatologic, infectious, and neoplastic disorders. Moreover, the
      etiology of the eosinophilia in HESs can be primary (myeloid), secondary
      (lymphocyte-driven), or unknown. Although corticosteroids remain the first-line
      therapy for most forms of HESs, the availability of an increasing number of novel
      therapeutic agents, including tyrosine kinase inhibitors and monoclonal
      antibodies, has necessarily altered the approach to treatment of HESs. This
      review presents an updated treatment-based approach to the classification of
      patients with presumed HES and discusses the roles of conventional and novel
      agents in the management of these patients. 

PMID- 25964672
TI  - The role of pathogen genomics in assessing disease transmission.
AB  - Whole genome sequencing (WGS) of pathogens enables the sources and patterns of
      transmission to be identified during specific disease outbreaks and promises to
      transform epidemiological research on communicable diseases. This review
      discusses new insights into disease spread and transmission that have come from
      the use of WGS, particularly when combined with genomic scale phylogenetic
      analyses. These include elucidation of the mechanisms of cross species
      transmission, the potential modes of pathogen transmission, and which people in
      the population contribute most to transmission. Particular attention is paid to
      the ability of WGS to resolve individual patient to patient transmission events.
      Importantly, WGS data seem to be sufficiently discriminatory to target cases
      linked to community or hospital contacts and hence prevent further spread, and to
      investigate genetically related cases without a clear epidemiological link.
      Approaches to combine evidence from epidemiological with genomic sequencing
      observations are summarised. Ongoing genomic surveillance can identify
      determinants of transmission, monitor pathogen evolution and adaptation, ensure
      the accurate and timely diagnosis of infections with epidemic potential, and
      refine strategies for their control. 

PMID- 25964673
TI  - Prospects for the NHS in England in the next parliament.

PMID- 25964674
TI  - Duke University settles lawsuits alleging that patients were harmed in
      chemotherapy trials.

PMID- 25964675
TI  - Woman asks court for right to use dead daughter's eggs to produce grandchild.

PMID- 25964676
TI  - Research is stifled by "regulation and conservatism," conference hears.

PMID- 25964677
TI  - Expert criticises report that said UK's maternal death rate was twice that of
      Belarus.

PMID- 25964678
TI  - Margaret McCartney: Daily drug shortages place avoidable pressure on primary
      care.

PMID- 25964679
TI  - Applying new evidence into practice: a need for knowledge translation.

PMID- 25964680
TI  - [Not Available].

PMID- 25964681
TI  - Occupational exposure to chemotherapy of pharmacy personnel at a single centre.
AB  - BACKGROUND: Cyclophosphamide is one of the most commonly used chemotherapy drugs
      worldwide. Data concerning environmental contamination and biological exposure of
      pharmacy personnel to this and other chemotherapy drugs are limited. OBJECTIVES:
      To determine whether pharmacy personnel involved in preparing and checking
      cyclophosphamide doses were more likely to have detectable levels of this drug in
      their urine than non-oncology pharmacy personnel with no known contact with the
      drug, and to compare the degree of surface contamination with cyclophosphamide,
      methotrexate, and ifosfamide in the oncology pharmacy of a tertiary care
      pediatric hospital, where chemotherapy doses were prepared, and the main
      (control) pharmacy in the same institution, where no chemotherapy was prepared.
      METHODS: Biological exposure to cyclophosphamide was compared between pharmacy
      personnel who did and did not handle this drug by determining whether
      participants had detectable amounts of cyclophosphamide in their urine.
      Environmental exposure to chemotherapy drugs was assessed by using surface wipes
      to determine the degree of surface contamination with various chemotherapy agents
      in the oncology pharmacy and the main (control) pharmacy. RESULTS: On initial
      testing, cyclophosphamide was detected in the urine of all pharmacy personnel (n
      = 7 oncology personnel, n = 5 control personnel). However, it was determined that
      all control personnel had been exposed to the oncology pharmacy on the day of
      testing. Repeat testing of these individuals revealed no positive samples among
      those not exposed to the oncology pharmacy on the day of repeat testing. The sole
      positive result on retesting of control personnel was for a participant who had
      been exposed to the oncology pharmacy on the retest day. Surface wipe testing
      revealed contamination of the oncology pharmacy with cyclophosphamide and
      methotrexate before and after cleaning, as well as contamination with ifosfamide
      after cleaning. The main (control) pharmacy showed no evidence of contamination
      with cyclophosphamide, methotrexate, or ifosfamide. CONCLUSIONS: The findings
      suggest that environmental contamination plays a role in biological exposure to
      cyclophosphamide. Measures to reduce environmental contamination from
      chemotherapy and biological exposure of pharmacy personnel when handling
      chemotherapy agents should be identified and implemented as a priority.

PMID- 25964682
TI  - Rapid Reduction in Use of Antidiabetic Medication after Laparoscopic Sleeve
      Gastrectomy: The Newfoundland and Labrador Bariatric Surgery Cohort (BaSCo)
      Study.
AB  - BACKGROUND: Patients who have undergone bariatric surgery generally need fewer
      medications as they experience improvement in, or even resolution of, various
      medical conditions, including type 2 diabetes mellitus, hypertension, and
      dyslipidemia. Published data on changes in medication use after laparoscopic
      sleeve gastrectomy, a type of bariatric surgery that is growing in popularity,
      are limited. OBJECTIVE: To determine whether patients took fewer medications for
      management of type 2 diabetes, hypertension, and dyslipidemia after laparoscopic
      sleeve gastrectomy, relative to preprocedure medications. METHODS: In this
      prospective, single-centre cohort study, a nurse practitioner used standard
      medication reconciliation and study data-extraction forms to interview adult
      patients who had undergone laparoscopic sleeve gastrectomy and determine their
      medication use and pertinent demographic data. The data were analyzed using
      generalized estimating equations and standard statistical software. Outcome
      measures included changes in the use of antidiabetic, antihypertensive, and
      antilipemic medications at 1, 3, and 6 months after the surgery. RESULTS: A total
      of 65 patients who underwent laparoscopic sleeve gastrectomy between May 2011 and
      January 2014 met the study inclusion criteria. Before surgery, the 30 patients
      with type 2 diabetes were taking an average of 1.9 antidiabetic medications. One
      month after the procedure, 15 (50%) had discontinued all antidiabetic
      medications, with a further decline at 3 and 6 months (p < 0.001 at each time
      point). Among the patients who were taking antihypertensives (n = 48) and
      antilipemics (n = 33) before surgery, the decline in use occurred at a more
      modest rate, with 6 (12%) and 2 (6%), respectively, discontinuing these
      medication classes within 1 month, and 12 (25%) (p = 0.001) and 8 (24%) (p =
      0.015) having discontinued by 6 months. CONCLUSIONS: These findings suggest that
      patients with a history of type 2 diabetes mellitus, hypertension, and/or
      dyslipidemia who undergo laparoscopic sleeve gastrectomy are less likely to
      require disease-specific medications shortly after surgery.

PMID- 25964683
TI  - Stability of Ertapenem 100 mg/mL in Manufacturer's Glass Vials or Syringes at 4
      degrees C and 23 degrees C.
AB  - BACKGROUND: Prophylactic administration of ertapenem as a single 1-g IV dose has
      been shown to reduce sepsis after prostate biopsy. OBJECTIVE: To evaluate the
      stability of ertapenem after reconstitution with 0.9% sodium chloride to a final
      concentration of 100 mg/mL and storage in the manufacturer's original glass vials
      or polypropylene syringes. METHODS: On study day 0, 100 mg/mL solutions of
      ertapenem were retained in the manufacturer's glass vials or packaged in
      polypropylene syringes and stored at 4 degrees C or 23 degrees C without
      protection from fluorescent room light. Samples were assayed periodically over 18
      days using a validated, stability-indicating liquid chromatographic method with
      ultra-violet detection. A beyond-use date was determined as the time for the
      concentration to decline to 90% of the initial (day 0) concentration, based on
      the fastest degradation rate, with 95% confidence. RESULTS: Reconstituted
      solutions stored in the manufacturer's glass vials or polypropylene syringes
      exhibited a first-order degradation rate, such that 10% of the initial
      concentration was lost in the first 2.5 days when stored at 4 degrees C or within
      the first 6.75 h when stored at room temperature (23 degrees C). Analysis of
      variance showed differences in the percentage remaining due to temperature (p <
      0.001) and study day (p < 0.001) but not type of container (p = 0.98). When a 95%
      CI for the degradation rate was calculated and used to determine a beyond-use
      date, it was established that more than 90% of the initial concentration would
      remain for 2.35 days at 4 degrees C and for 0.23 day (about 5 h, 30 min) at room
      temperature. CONCLUSIONS: A 100 mg/mL ertapenem solution stored in the
      manufacturer's glass vial or a polypropylene syringe will retain more than 90.5%
      of the initial concentration when stored for 48 h at 4 degrees C and for an
      additional 1 h at 23 degrees C.

PMID- 25964684
TI  - Professional Culture and Personality Traits of Hospital Pharmacists across
      Canada: A Fundamental First Step in Developing Effective Knowledge Translation
      Strategies.
AB  - BACKGROUND: Evidence for the value of pharmacists' interventions in the care of
      patients is strong and continues to grow, but the rate at which these new
      practice opportunities are being integrated into daily practice has not kept
      pace. The knowledge translation literature suggests that before effective change
      strategies can be implemented, a better understanding of the current environment
      must be obtained. Two important factors within the practice environment are the
      professional culture and personality traits of group members. OBJECTIVE: To gain
      insight, at a national level, into the culture of hospital pharmacy, using the
      Organizational Culture Profile, and into hospital pharmacists' personality
      traits, using the Big Five Inventory. METHODS: A cross-sectional survey of
      hospital pharmacists from across Canada was conducted intermittently over the
      period August 2012 to September 2013. The online survey contained questions about
      demographic characteristics and practice setting, as well as questions from the
      Organizational Culture Profile and Big Five Inventory. The survey link was
      distributed directly to hospital pharmacists or made available through provincial
      monthly newsletters. All data were analyzed descriptively and inferentially.
      RESULTS: In total, 401 surveys were returned. Descriptive analyses from the
      Organizational Culture Profile revealed that most respondents perceived value in
      the factors of supportiveness, competitiveness, and stability. Descriptive
      analyses from the Big Five Inventory revealed that respondents may have been more
      likely to exhibit behaviours in line with the trait of conscientiousness. Several
      significant subgroup differences were noted in relation to levels of education,
      regions of practice within Canada, years in practice, and proportion of time
      spent conducting clinical duties. CONCLUSIONS: The results from this survey
      provide preliminary insight into the professional culture and personality traits
      of Canadian hospital pharmacists. It will be important to explore these findings
      in more depth to maximize the success of any future practice change initiatives.

PMID- 25964686
TI  - Systematic reviews: what do you need to know to get started?

PMID- 25964685
TI  - Risk Factors for and Outcomes of Bacteremia Caused by Extended-Spectrum beta
      Lactamase-Producing Escherichia coli and Klebsiella Species at a Canadian
      Tertiary Care Hospital.
AB  - BACKGROUND: Antimicrobial resistance due to production of extended-spectrum beta
      lactamases by Escherichia coli and Klebsiella species (ESBL-EK) is concerning.
      Previous studies have shown that bacteremia due to ESBL-producing organisms is
      associated with increases in length of stay and/or mortality rate. Rates of
      infection by ESBL-EK vary worldwide, and regional differences in the prevalence
      of risk factors are likely. Few Canadian studies assessing risk factors for ESBL
      EK infections or the outcomes of empiric therapy have been published. OBJECTIVES:
      To determine risk factors for and patient outcomes associated with ESBL-EK
      bacteremia. The appropriateness of empiric antibiotic therapy and the effect of
      inappropriate empiric therapy on these outcomes were also examined. METHODS: In a
      retrospective, 1:1 case-control study conducted in a tertiary care hospital
      between 2005 and 2010, data for 40 patients with ESBL-EK bacteremia were compared
      with data for 40 patients who had non-ESBL-EK bacteremia. RESULTS: Of all
      variables tested, only antibiotic use within the previous 3 months was found to
      be an independent risk factor for acquisition of ESBL-EK bacteremia (odds ratio
      5.2, 95% confidence interval 1.6-16.9). A greater proportion of patients with non
      ESBL-EK bacteremia received appropriate empiric therapy (88% [35/40] versus 15%
      [6/40], p < 0.001). Time to appropriate therapy was longer for those with ESBL-EK
      bacteremia (2.42 days versus 0.17 day, p < 0.001). Patient outcomes, including
      length of stay in hospital, admission to the intensive care unit (ICU), length of
      stay in the ICU (if applicable), and in-hospital mortality were not affected by
      the presence of ESBL-EK or the appropriateness of empiric therapy. CONCLUSIONS:
      Previous antibiotic use was a significant, independent risk factor for acquiring
      ESBL-EK. Thus, prior antibiotic use is an important consideration in the
      selection of empiric antibiotic therapy and should increase the concern for
      resistant pathogens.

PMID- 25964687
TI  - [Not Available].

PMID- 25964688
TI  - Staff pharmacists' perspectives on contemporary pharmacy practice issues.

PMID- 25964689
TI  - Warfarin Re-initiation Gone Awry: A Case of Inadvertent Overdose Mandating
      Critical INR Management.

PMID- 25964690
TI  - Are Decentralized Pharmacy Services the Preferred Model of Pharmacy Service
      Delivery within a Hospital?

PMID- 25964691
TI  - Ebola virus disease: what canadian hospital pharmacists need to know.

PMID- 25964693
TI  - [Not Available].

PMID- 25964692
TI  - Tribute to the reviewers of the canadian journal of hospital pharmacy.

PMID- 25964694
TI  - Pharmacy awareness: a continuous process.

PMID- 25964695
TI  - NIECR--a quiet revolution.

PMID- 25964696
TI  - The Thinking Doctor's Ward Round.

PMID- 25964697
TI  - From Hippocrates to the Francis Report--Reflections on empathy.

PMID- 25964698
TI  - Non-pharmacological management of chronic obstructive pulmonary disease.

PMID- 25964699
TI  - Domiciliary non-invasive ventilation in the elderly. Effective, tolerated and
      justified.
AB  - AIM: To determine if the long terms effects of non-invasive home mechanical
      ventilation (NIHMV) in the elderly are as beneficial as in younger subjects for a
      dedicated non-invasive ventilation unit in a tertiary referral hospital within
      the UK. PATIENTS AND METHODS: The study population included 256 patients who were
      successfully established on NIHMV between May 2009 and August 2013. Patients were
      divided into three groups according to age: group 1 (n=103) >=75; group 2 (n=81)
      65 -74; and group 3 (n=72) < 65 years of age. Initial assessments, both prior to
      starting NIHMV and at 12 month follow up were determined which included
      establishing the primary cause of respiratory insufficiency, measurement of
      arterial blood gas parameters, spirometry, overnight oximetry, and sniff nasal
      inspiratory pressure (SNIP) in those patients with neuromuscular disease. The
      number of hospital admissions in the year prior to starting NIHMV, and in the
      subsequent year, along with the number of days spent as an inpatient were
      ascertained as a measure of burden to local health care resources. Compliance
      with NIV at follow up, facilitated by recorded data within the ventilator
      software, was established along with an assessment of any reported side effects.
      RESULTS: Group 3 had the most profound abnormalities in lung function and blood
      gas parameters at initial assessment with a trend towards a higher number of
      acute admissions. In absolute terms, there was a greater decline in the number of
      admissions for subjects in group 2 after being established on NIHMV. Although
      more subjects in group 3 had chest wall deformities, COPD or bronchiectasis, this
      group had the lowest number of subjects with neuromuscular disease. Improvements
      in gas exchange were most pronounced for group 3 subjects despite no significant
      differences in the selected ventilator settings across the 3 groups. For
      neuromuscular patients, when measured, SNIP pressures were lowest in group 3.
      CONCLUSION: NIHMV was effective and tolerated for all three age groups. There was
      an improvement in measured patient centred endpoints across all three age groups,
      all of whom benefited equally.

PMID- 25964700
TI  - Parathyroid Glands response to Low Vitamin D levels in Healthy Adults: A Cross
      Sectional Study.
AB  - OBJECTIVE: To assess the correlation of serum parathyroid hormone (PTH) and
      vitamin D (25-OHD) levels based on different assays for measuring 25-OHD in
      healthy Saudi Arabians living along the east coast. PATIENTS AND METHODS: A cross
      sectional study was conducted in 200 patients (150 women and 50 men aged between
      18-69 years) between January 2011 and December 2012, attending outpatient clinic
      at King Fahd Hospital of the University, Al Khobar. The first 200 patients seen
      without vitamin D supplementation at clinic were enrolled in the study. Serum
      calcium, phosphorous, alkaline phosphatase, parathormone, and 25-OHD tests were
      performed. 25-OHD was assessed using:chemiluminescence immunoassay
      (CLIA)radioimmunoassay (RIA) using Wallac 1470 Gamma CounterHPLC -LC.MS (high
      performance liquid chromatography-liquid chromatography with mass spectrometry.
      The data was collected, entered into a database and analysed using SPSS, Inc.,
      version 14. RESULTS: The mean age was 45.8+/-15.8 (18-74) years, and calcium
      level was 2.27+/-0.15 mmol/l. (range 2.125 to 2.62 mmol/l). Alkaline phosphatase
      was 88.91+/-35.94 (34-302) IU, parathormone 6.7+/-3.06 (1.35-21.2) (1.3-6.8
      pmol/l). Of the participants, 188 were either vitamin D insufficient or deficient
      as measured by CLIA 11.85+/-6.14 (2-29.6), and 91 (48.4%) of them had secondary
      hyperparathyroidism 9.48+/-4.55 pc/l. Those with normal CLIA-measured 25-OHD
      levels had normal PTH levels. Of those with insufficiency, 4/21 (19%) had raised
      PTH levels; and of those with deficiency, 81/166 (48.79%) had raised levels,
      whereas with HPLC-LC.MS, 156 were shown to be insufficient and 97 deficient (with
      PTH level of 7.41+/-4.2). Thirteen of 41 patients (31.7%) with insufficiency were
      shown, by HPLC-LC.MS, to have raised PTH. All patients with vitamin D deficiency
      as diagnosed by HPLC-LC.MS had secondary hyperparathyroidism. CONCLUSIONS: The
      above results suggest that the method of measurement strongly influences vitamin
      D levels and that previous reports suggesting no association between vitamin D
      deficiency and secondary hyperparathyroidism should be viewed with caution.

PMID- 25964702
TI  - Teaching Medical Students, what do Consultants think?
AB  - BACKGROUND: The approach to and delivery of medical student education has
      undergone significant change within the last decade. There has been a shift away
      from didactic lectures to small group tutorials, facilitated by clinicians.
      Anecdotally there is an impression that enthusiasm for teaching is waning. The
      aim of this qualitative study is to assess the current attitudes of consultants,
      across all specialities, to teaching medical students in small group settings.
      METHODS: A Likert scale questionnaire, relating to teaching medical students in
      small group tutorials, was distributed via email to all consultants working in
      one region. Questions considered the categories: attitudes to teaching, financial
      considerations, time constraints and attitudes to students. RESULTS: 367
      responses were received. 72% of responders were actively involved in teaching.
      72% of respondents indicated that medical students should be taught by
      consultants and 80% felt that teaching medical students was enjoyable. 60% felt
      they were not financially remunerated for teaching and 50% indicated teaching was
      not included in job plans; despite this a significant proportion of these
      respondents remain involved in teaching (68%). Non-teachers were more likely to
      indicate that teaching was not paid for (p=0.003). 78% indicated consultants do
      not have adequate time to teach medical students. 82% felt that medical students
      appreciate consultant led teaching but only 55% felt students had an appropriate
      level of enthusiasm for learning. CONCLUSION: Consultants in this Deanery are
      actively involved in medical student teaching and enjoy it. Consultants perceive
      that they are not adequately financially rewarded but for the most part this is
      not a deterrent. Time constraints are an issue and there is a desire to have
      teaching included in job plans to counteract this. Most consultants are
      complimentary about student attitudes but there is a perception that medical
      students need to contribute more to their own learning.

PMID- 25964703
TI  - Historical Development of Pan-European Medical Training for English speaking
      students in the 16th to 19th Centuries.

PMID- 25964701
TI  - A novel approach to improve undergraduate surgical teaching.
AB  - BACKGROUND: Undergraduate surgery is at an important crossroads. Many departments
      report significant difficulties delivering effective teaching. Our student
      feedback indicated a dated surgical curriculum lacking structure, quality and
      uniformity. We report on a new "blended" approach employing a combination of
      professional DVDs, case based discussions, online material and traditional
      bedside teaching designed to provide structure, standardization, and equality of
      learning . METHODS: Year 4 students who had undertaken the new course and year 5
      students who had participated in the traditional teaching programme were
      compared. Students completed a 20 item questionnaire about their experiences of
      the surgical teaching programme. RESULTS: One hundred and seventy-one year 4
      (70%) and 148 year 5 students (66%) responded. Domains relating to "Overall
      Satisfaction with the course", "Approval of innovative teaching methods and
      interactivity" and "Satisfaction with the clarity of course information" showed
      improvements when comparing the new and old programmes. However bedside teaching
      was not rated as highly in the new programme (p<0.05). CONCLUSION: This blended
      approach has resulted in improved student understanding and engagement. The
      apparent compromise of bedside teaching may be a reflection of higher
      expectations. We believe that a similar blended approach has the potential to re
      invigorate surgical teaching elsewhere.

PMID- 25964704
TI  - From the archives: the Ulster Medical Journal, April 1934, Volume 3, Number 2.

PMID- 25964705
TI  - Follicular lesions of the thyroid: a surgical perspective.

PMID- 25964706
TI  - James Logan Prize Essay. The challenges of cancer pain assessment.

PMID- 25964709
TI  - So you want to be a Specialty Doctor.

PMID- 25964710
TI  - Context-specific method for detection of soft-tissue lesions in non-cathartic low
      dose dual-energy CT colonography.
AB  - In computed tomographic colonography (CTC), orally administered fecal-tagging
      agents can be used to indicate residual feces and fluid that could otherwise hide
      or imitate lesions on CTC images of the colon. Although the use of fecal tagging
      improves the detection accuracy of CTC, it can introduce image artifacts that may
      cause lesions that are covered by fecal tagging to have a different visual
      appearance than those not covered by fecal tagging. This can distort the values
      of image-based computational features, thereby reducing the accuracy of computer
      aided detection (CADe). We developed a context-specific method that performs the
      detection of lesions separately on lumen regions covered by air and on those
      covered by fecal tagging, thereby facilitating the optimization of detection
      parameters separately for these regions and their detected lesion candidates to
      improve the detection accuracy of CADe. For pilot evaluation, the method was
      integrated into a dual-energy CADe (DE-CADe) scheme and evaluated by use of leave
      one-patient-out evaluation on 66 clinical non-cathartic low-dose dual-energy CTC
      (DE-CTC) cases that were acquired at a low effective radiation dose and
      reconstructed by use of iterative image reconstruction. There were 22 colonoscopy
      confirmed lesions >=6 mm in size in 21 patients. The DE-CADe scheme detected 96%
      of the lesions at a median of 6 FP detections per patient. These preliminary
      results indicate that the use of context-specific detection can yield high
      detection accuracy of CADe in non-cathartic low-dose DE-CTC examinations.

PMID- 25964711
TI  - Differential response of wild and cultivated wheats to water deficits during
      grain development: changes in soluble carbohydrates and invertases.
AB  - Wheat, staple food crop of the world, is sensitive to drought, especially during
      the grain-filling period. Water soluble carbohydrates (WSCs), stem reserve
      mobilization and higher invertase activity in the developing grains are important
      biochemical traits for breeding wheat to enhance tolerance to terminal drought.
      These traits were studied for three accessions of Triticum dicoccoides(a
      tetraploid wheat progenitor species) - acc 7054 (EC 171812), acc 7079 (EC 171837)
      and acc 14004 (G-194-3 M-6 M) selected previously on the basis of grain filling
      characteristics. Check wheat cultivars- PBW-343 (a popular bread wheat cultivar
      for irrigated environments) and C-306 (widely adapted variety for rain-fed
      agriculture) were also included in this set. Analysis of variance revealed
      significant genotypic differences for the content of water soluble carbohydrates,
      activity of acid invertase and alkaline invertase. Acc 7079 was found to be a
      very efficient mobilizer of water soluble carbohydrates (236.43 mg g(-1) peduncle
      DW) when averaged over irrigated and rain-fed conditions. Acid invertase activity
      revealed marked genotypic differences between wild and cultivated wheats.
      Alkaline invertase activity was highest in Acc 7079 when pooled across both the
      environments. On the whole, acc 7079 qualifies as a suitable donor for enhancing
      tolerance of bread wheat to terminal drought. The association of physio
      biochemical differences observed with grain filling attributes on one hand and
      molecular markers on the other could be of use in improving wheat for water
      stress conditions. 

PMID- 25964712
TI  - Quantitative expression analysis of drought responsive genes in clones of Hevea
      with varying levels of drought tolerance.
AB  - In order to meet the ever rising global demand for natural rubber, cultivation of
      Hevea is being extended to non-traditional regions of India where extreme
      climatic conditions like drought and low temperature negatively influence the
      crop performance. In order to ensure maximum productivity, identification of
      drought tolerant clones of Hevea which can cope up with stress and give better
      crop yield is essential. Several attempts have been made previously to identify
      genes that are associated with drought tolerance in Hevea. In the present study,
      quantitative expression analysis was made using quantitative PCR for seven
      drought associated transcripts in four clones of Hevea with varying levels of
      drought tolerance. Among the seven genes studied, Mitogen Activated Protein (MAP)
      kinase, Myeloblastosis (Myb) transcription factor, C-repeat responsive
      element/Dehydration Responsive Element (CRT/DRE) binding factor and Nuclear
      Factor Y subunit A (NFYA) showed a positive association with drought tolerance.
      Transcripts of ascorbate peroxidase and heat shock protein 70 (HSP 70) did not
      show any correlation with drought tolerance. Interestingly, catalase gene was
      found down regulated in all the clones under drought condition. The possible role
      of these genes based on their level of gene expression in four different clones
      of Hevea with varying levels of drought tolerance is discussed. 

PMID- 25964713
TI  - Transcriptional profiling in pearl millet (Pennisetum glaucum L.R. Br.) for
      identification of differentially expressed drought responsive genes.
AB  - Pearl millet (Pennisetum glaucum) is an important cereal of traditional farming
      systems that has the natural ability to withstand various abiotic stresses. The
      present study aims at the identification and validation of major differentially
      expressed genes in response to drought stress in P. glaucum by Suppression
      Subtractive Hybridization (SSH) analysis. Twenty-two days old seedlings of P.
      glaucum cultivar PPMI741 were subjected to drought stress by treatment of 30 %
      Polyethylene glycol for different time periods 30 min (T1), 2 h (T2), 4 h (T3), 8
      h (T4), 16 h (T5), 24 h (T6) and 48 h (T7) respectively, monitored by examining
      the RWC of seedlings. Total RNA was isolated to construct drought responsive
      subtractive cDNA library through SSH, sequenced to identify the differentially
      expressed genes in response to drought stress and validated by qRT-PCR.745 ESTs
      were assembled into a collection of 299 unigenes having 52 contigs and 247
      singletons. All 745 ESTs were submitted to ENA-EMBL databases (Accession no.
      HG516611- HG517355). After analysis, 10 differentially expressed genes were
      validated namely Abscisic stress ripening protein, Ascorbate peroxidase, Inosine
      5'-monophosphate dehydrogenase, Putative beta-1, 3-glucanase, Glyoxalase, Rab7,
      Aspartic proteinase Oryzasin, DnaJ-like protein and Calmodulin-like protein by
      qRT-PCR. The identified ESTs reveal a major portion of the stress responsive
      transcriptome that may prove to be a vent to unravel molecular basis underlying
      tolerance of pearl millet (Pennisetum glaucum) to drought stress. These genes
      could be utilized for transgenic breeding or transferred to crop plants through
      marker assisted selection for the development of better drought resistant
      cultivars having enhanced adaptability to survive harsh environmental conditions.

PMID- 25964714
TI  - Biological seed priming mitigates the effects of water stress in sunflower
      seedlings.
AB  - The sunflower (Helianthus annuus L. cv. PAC 36) seedlings were inoculated with
      plant growth promoting rhizobacteria (PGPR), viz. Azotobacter chroococcum (A+),
      Bacillus polymyxa (B+), separately and in combination of the two (AB+). Relative
      water content and seedling growth were maximum in AB+ seedlings under control.
      Water stress significantly decreased the RWC, growth and dry mass of non
      inoculated seedlings. However, inoculated seedlings maintained higher growth even
      under water stress. Pigments and protein contents decreased under water stress,
      but higher amount of the same was observed in stressed AB+ seedlings. Enhanced
      activity of nitrate reductase was recorded in AB+ seedlings with maximum in
      control. Water stress significantly decreased the nitrate reductase activity. A
      significant increase in the activity of superoxide dismutase (SOD) in leaves was
      recorded under water stress except in B+ with maximum increase in non-inoculated
      seedlings. Catalase (CAT) activity decreased in stressed non-inoculated seedlings
      while increased in the leaves of A+ and AB+ seedlings. Almost similar trends were
      recorded for both leaves and cotyledons. PGPR improved the water status in
      stressed seedlings and thereby physiological and biochemical parameters and thus
      ameliorated the severe effects of water stress. 

PMID- 25964715
TI  - Influence of exogenous application of glycinebetaine on antioxidative system and
      growth of salt-stressed soybean seedlings (Glycine max L.).
AB  - Glycinebetaine is one of the most competitive compounds which play an important
      role in salt stress in plants. In this study, the enhanced salt tolerance in
      soybean (Glycine max L.) by exogenous application of glycinebetaine was
      evaluated. To improve salt tolerance at the seedling stage, GB was applied in
      four different concentrations (0, 5, 25 and 50 mM) as a pre-sowing seed
      treatment. Salinity stress in the form of a final concentration of 150 mM sodium
      chloride (NaCl) over a 15 day period drastically affected the plants as indicated
      by increased proline, MDA and Na(+) content of soybean plants. In contrast,
      supplementation with 50 mM GB improved growth of soybean plants under NaCl as
      evidenced by a decrease in proline, MDA and Na(+) content of soybean plants.
      Further analysis showed that treatments with GB, resulted in increasing of CAT
      and SOD activity of soybean seedlings in salt stress. We propose that the role of
      GB in increasing tolerance to salinity stress in soybean may result from either
      its antioxidant capacity by direct scavenging of H2O2 or its role in activating
      CAT activity which is mandatory in scavenging H2O2. 

PMID- 25964716
TI  - Assessment of genetic diversity in indigenous turmeric (Curcuma longa) germplasm
      from India using molecular markers.
AB  - Curcuma longa L., commonly known as turmeric, is one of the economically and
      medicinally important plant species. It is predominantly cultivated in the
      tropical and sub tropical countries. India is the largest producer, and exporter
      of turmeric in the world, followed by China, Indonesia, Bangladesh and Thailand.
      In the present study, Directed Amplification of Minisatellite DNA (DAMD) and
      Inter Simple Sequence Repeats (ISSR), methods were used to estimate the genetic
      variability in indigenous turmeric germplasm. Cumulative data analysis for DAMD
      (15) and ISSR (13) markers resulted into 478 fragments, out of which 392
      fragments were polymorphic, revealing 82 % polymorphism across the turmeric
      genotypes. Wide range of pairwise genetic distances (0.03-0.59) across the
      genotypes revealed that these genotypes are genetically quite diverse. The UPGMA
      dendrogram generated using cumulative data showed significant relationships
      amongst the genotypes. All 29 genotypes studied grouped into two clusters
      irrespective of their geographical affiliations with 100 % bootstrap value except
      few genotypes, suggesting considerable diversity amongst the genotypes. These
      results suggested that the current collection of turmeric genotypes preserve the
      vast majority of natural variations. The results further demonstrate the
      efficiency and reliability of DAMD and ISSR markers in determining the genetic
      diversity and relationships among the indigenous turmeric germplasm. DAMD and
      ISSR profiling have identified diverse turmeric genotypes, which could be further
      utilized in various genetic improvement programmes including conventional as well
      as marker assisted breeding towards development of new and desirable turmeric
      genotypes. 

PMID- 25964717
TI  - Validation of SSR markers associated with rust (Uromyces fabae) resistance in pea
      (Pisum sativum L.).
AB  - Pea rust is a devastating disease of peas especially in the sub-tropical regions
      of the world and greatly influenced by the environmental conditions during
      disease development. Molecular markers associated with pea rust resistance would
      be useful in marker assisted selection (MAS). Utility of molecular markers
      associated with the pea rust resistance were evaluated in 30 diverse pea
      genotypes using four SSR markers (AA446 and AA505 flanking the major QTL Qruf;
      AD146 and AA416 flanking the minor QTL, Qruf1). QTL, Qruf flanking markers were
      able to identify all the resistant genotypes when used together, except Pant P
      31. While, SSR markers AD146 and AA416 flanking the minor QTL, Qruf1 were able to
      identify all the pea resistant genotypes used for validation, except for HUDP-11
      by AD146 and Pant P 31 by AA416. Similarly, SSR markers AA446 and AA505 were able
      to identify all the susceptible pea genotypes, except IPFD 99-13, HFP 9415 and S-
      143. SSR markers AD146 and AA416 were together able to identify all the pea
      susceptible genotypes used for validation, except KPMR 526, KPMR 632 and IPFD 99
      13. On the basis of marker allele analysis it may be concluded that SSR markers
      (AA446, AA505, AD146 and AA416) can be used in MAS of pea rust resistance. 

PMID- 25964718
TI  - Efficient shoots regeneration and genetic transformation of Bacopa monniera.
AB  - Bacopa monniera is an important source of metabolites with pharmaceutical value.
      It has been regarded as a valuable medicinal plant and its entire commercial
      requirement is met from wild natural population. Recently, metabolic engineering
      has emerged as an important solution for sustained supply of assured and quality
      raw material for the production of active principles. Present report describes
      efficient in vitro multiplication and transformation method for genetic
      manipulation of this species. MS medium supplemented with 2 mgl(-1) BA and 0.2
      mgl(-1) IAA was found optimum for maximum shoot regeneration (98.33 %) from in
      vitro leaves with 2-3 longitudinal cuts. Agrobacterium tumefaciens-mediated
      transformation method was used for generating transgenic B. monniera plants.
      Putative transformants were confirmed by GUS assay and PCR based confirmation of
      hptII gene. DNA blot analysis showed single copy insertion of transgene cassette.
      An average of 87.5 % of the regenerated shoots were found PCR positive for hptII
      gene and GUS activity was detected in leaves of transgenic shoots at a frequency
      of 82.5 % The efficient multiple shoots regeneration system described herein may
      help in mass production of B. monniera plant. Also, the high frequency
      transformation protocol described here can be used for genetic engineering of B.
      monniera for enhancement of its pharmaceutically important metabolites. 

PMID- 25964719
TI  - Plant regeneration from organogenic callus and assessment of clonal fidelity in
      Elephantopus scaber Linn., an ethnomedicinal herb.
AB  - An efficient callus induction and plant regeneration system has been standardized
      for an ethnomedicinal plant, Elephantopus scaber Linn. Two explants i. e. seeds
      and leaf segments were used for callus induction. Murashige and Skoog (MS) medium
      supplemented with 5.0 MUM 2, 4-dichlorophenoxy acetic acid (2, 4-D) and 0.5 MUM
      kinetin (Kn) gave the optimum frequency (89 %) of callus induction from seed
      explant. The results showed that the highest response in terms of percent callus
      regenerating (91 %) and number of shoots (56) per culture was recorded on MS
      medium supplemented with 6.0 MUM N6-benzylaminopurine (BA) and 1.5 MUM alpha
      naphthalene acetic acid (NAA). The best rooting of regenerated shoots was
      obtained on half strength MS medium supplemented with 6.0 MUM indole-3- butyric
      acid (IBA). On this medium, 100 % of the shoots produced roots with a mean number
      of 3.2 roots per shoot. The positive role of vesicular arbuscular mycorrhizae
      (VAM) along with potting mix has been well established in the present study. Of
      the various potting mix employed for plant acclimatization, the highest response
      of 100 % plant survival was noticed when autoclaved garden soil, sand (2:1) and
      VAM was utilized as potting mix. Inter-simple sequence repeats (ISSR) were used
      to establish the clonal fidelity of regenerated plantlets and the banding
      profiles from callus derived plants were monomorphic and similar to those of
      mother plant, thus ascertaining the true-to-type nature of these plants. 

PMID- 25964720
TI  - High frequency organogenesis in hypocotyl, cotyledon, leaf and petiole explants
      of broccoli (Brassica oleracea L. var. italica), an important vegetable crop.
AB  - Broccoli (Brassica oleracea L. var. italica) is an important, nutritionally rich
      vegetable crop, but severely affected by environmental stresses, pests and
      diseases which cause massive yield and quality losses. Genetic manipulation is
      becoming an important method for broccoli improvement. In the present study, a
      reproducible and highly efficient protocol for obtaining organogenesis from
      hypocotyl, cotyledon, leaf and petiole explants of broccoli (Brassica oleracea L.
      var. italica cv. Solan green head) has been developed. Hypocotyl and cotyledon
      explants were used from 10 to 12 days old aseptically grown seedlings whereas
      leaf and petiole explants were excised from 18 to 20 days old green house grown
      seedlings and surface sterilized. These explants were cultured on shoot induction
      medium containing different concentration and combination of BAP and NAA. High
      efficiency shoot regeneration has been achieved in hypocotyl (83.33 %), cotyledon
      (90.11 %), leaf (62.96 %) and petiole (91.10 %) explants on MS medium
      supplemented with 3.5 mg/l BAP + 0.019 mg/l NAA 2.5 mg/l BAP + 0.5 mg/l NAA, 4.0
      mg/l BAP + 0.5 mg/l NAA and 4.5 mg/l BAP + 0.019 mg/l NAA respectively. Petiole
      explants showed maximum shoot regeneration response as compared to other
      explants. MS medium supplemented with 0.10 mg/l NAA was found best for root
      regeneration (100 %) from in vitro developed shoots. The regenerated complete
      plantlets were transferred to the pots containing cocopeat and successfully
      acclimatized. This optimized regeneration protocol can be efficiently used for
      genetic transformation in broccoli. This is the first comparative report on
      multiple shoot induction using four different types of explants viz. hypocotyl,
      cotyledon, leaf and petiole. 

PMID- 25964721
TI  - Direct adventitious shoot bud formation on hypocotyls explants in Millettia
      pinnata (L.) Panigrahi- a biodiesel producing medicinal tree species.
AB  - A reproducible protocol developed for in vitro regeneration of Milletia pinnata
      using hypocotyl segments. Multiple shoots were induced from hypocotyl explants
      through direct adventitious shoot bud regeneration. The proximal end of
      hypocotyls was responsive for shoot bud induction. Silver nitrate and adenine
      sulphate had a positive effect on shoot bud induction and elongation. The maximum
      response and number of shoot bud produced in media supplemented with 8.88 MUM BAP
      with 108.6 MUM adenine sulphate and 11.84 MUM silver nitrate. Elongated shoots
      were harvested and successful rooting of microshoots achieved on MS media
      supplemented with 9.84 MUM IBA, with 81.1 % rooting. Remaining shoot buds sub
      cultured for further multiplication and elongation. Each subculture produced
      eight to nine elongated microshoots up to four subcultures. The rooted
      microshoots were successfully hardened and transferred to field. 

PMID- 25964722
TI  - An efficient and reproducible indirect shoot regeneration from female leaf
      explants of Simmondsia chinensis, a liquid-wax producing shrub.
AB  - Simmondsia chinensis (Link) Schneider is a perennial, dioecious, drought
      resistant and multipurpose seed oil crop grown in arid and semi-arid conditions
      throughout the world. A reproducible and more efficient method for indirect shoot
      organogenesis from female leaf explants has been standardized. The leaf explants
      cultured on Murashige and Skoog (MS) medium with 1.0 mg l(-1) 2,4
      dichlorophenoxyacetic acid (2,4-D) alone produced the highest frequency of callus
      compared with 1.5 mg l(-1) IBA. Maximum proliferation of callus was observed on
      MS medium containing a combination of 1.0 mg l(-1) 2,4-D with 0.5 mg l(-1) BAP.
      For shoot differentiation, the proliferated callus was subcultured on MS medium
      supplemented with 6-benzylaminopurine (BAP) (1.0-4.0 mg l(-1)) along with 40 mg
      l(-1) adenine sulphate as additive or in combination with alpha-naphthalene
      acetic acid (NAA) or Indole-3-butyric acid (IBA). Optimum shoots differentiated
      from callus was obtained on MS medium supplemented with 2.0 mg l(-1) BAP and 0.2
      mg l(-1) NAA. On this medium, 100 % cultures were responded with an average
      number of 14.44 shoots per explant with their mean length of 4.78 cm. In vitro
      rooting (6.22 roots per explant) was achieved on half strength MS medium
      containing 2 % sucrose with 3.0 mg l(-1) IBA and 300 mg l(-1) activated charcoal
      (AC). Rooted plantlets were successfully hardened under control conditions and
      acclimatized under field conditions with 90 % success rate. The present protocol
      is highly efficient, reproducible and economically viable for large scale
      production of female plants. 

PMID- 25964723
TI  - Nucleotide variation and identification of novel blast resistance alleles of Pib
      by allele mining strategy.
AB  - Pib is one of significant rice blast resistant genes, which provides resistance
      to wide range of isolates of rice blast pathogen, Magnaporthe oryzae.
      Identification and isolation of novel and beneficial alleles help in crop
      enhancement. Allele mining is one of the best strategies for dissecting the
      allelic variations at candidate gene and identification of novel alleles. Hence,
      in the present study, Pib was analyzed by allele mining strategy, and coding and
      non-coding (upstream and intron) regions were examined to identify novel Pib
      alleles. Allelic sequences comparison revealed that nucleotide polymorphisms at
      coding regions affected the amino acid sequences, while the polymorphism at
      upstream (non-coding) region affected the motifs arrangements. Pib alleles from
      resistant landraces, Sercher and Krengosa showed better resistance than Pib donor
      variety, might be due to acquired mutations, especially at LRR region. The
      evolutionary distance, Ka/Ks and phylogenetic analyzes also supported these
      results. Transcription factor binding motif analysis revealed that Pib (Sr) had a
      unique motif (DPBFCOREDCDC3), while five different motifs differentiated the
      resistance and susceptible Pib alleles. As the Pib is an inducible gene, the
      identified differential motifs helps to understand the Pib expression mechanism.
      The identified novel Pib resistant alleles, which showed high resistance to the
      rice blast, can be used directly in blast resistance breeding program as
      alternative Pib resistant sources. 

PMID- 25964724
TI  - One-dimensional proteomic profiling of Danio rerio embryo vitellogenin to
      estimate quantum dot toxicity.
AB  - BACKGROUND: Vitellogenin (Vtg) is the major egg yolk protein (YP) in most
      oviparous species and may be useful as an indicator in ecotoxicological testing
      at the biochemical level. In this study, we obtained detailed information about
      the Vtgs of Danio rerio embryos by cutting SDS-PAGE gel lanes into thin slices,
      and analyzing them slice-by-slice with (MALDI-TOF) mass spectrometry. RESULTS: We
      conducted three proteomic analyses, comparing embryonic Danio rerio Vtg cleavage
      products after exposure for 48 h to CdSecore/ZnSshell quantum dots (QDs), after
      exposure to a mixture of the components used for quantum dot synthesis (MCS-QDs),
      and in untreated embryos. The Vtg mass spectrometric profiles of the QDs-treated
      embryos differed from those of the unexposed or MCS-QDs-treated embryos.
      CONCLUSION: This study demonstrates the possible utility of Vtg profiling in D.
      rerio embryos as a sensitive diagnostic tool to estimate nanoparticle toxicity.

PMID- 25964725
TI  - Levetiracetam in neonatal seizures: a review.
AB  - Phenobarbital and phenytoin have been the mainstay treatment modalities for
      neonatal seizures. Studies have revealed these agents control seizures in less
      than half of neonates, can cause neuronal apoptosis in vitro, and have highly
      variable pharmacokinetics in neonates. In contrast, there have been no reports of
      levetiracetam causing these neurotoxic effects. Due to its favorable side effect
      and pharmacokinetic profiles and positive efficacy outcomes in neonatal studies
      to date, there is great interest in the use of levetiracetam for neonatal
      seizures. This article reviews the literature regarding the safety of
      levetiracetam in neonates and its efficacy in neonatal seizures. 

PMID- 25964726
TI  - Reported rates of diarrhea following oral penicillin therapy in pediatric
      clinical trials.
AB  - OBJECTIVES: Antibiotic-associated diarrhea (AAD) is a well-recognized adverse
      reaction to oral penicillins. This review analyzed the literature to determine
      the incidence of AAD following amoxicillin, amoxicillin/clavulanate, and
      penicillin V oral therapy in pediatric clinical trials. METHODS: An advanced
      search was conducted in MEDLINE and Embase databases for articles in any language
      reporting the incidence of AAD following oral penicillin therapy for any
      indicated infection in children (0-17 years). The search was limited to clinical
      trials. Articles were excluded if treatment was related to chronic conditions,
      involved concomitant antimicrobials, or if the dose or number of patients was not
      specified. RESULTS: Four hundred thirty-five articles relating to clinical trials
      were identified (307 from Embase; 128 from MEDLINE). Thirty-five articles
      reporting on 42 studies were included for analysis. The indications included
      acute otitis media, sinusitis, pharyngitis, and pneumonia. Thirty-three trials
      reported on amoxicillin/clavulanate, 6 on amoxicillin, and 3 on penicillin V. In
      total, the 42 trials included 7729 children who were treated with an oral
      penicillin. On average, 17.2% had AAD. Data were pooled for each penicillin. The
      AAD incidence was 19.8% for amoxicillin/clavulanate, 8.1% for amoxicillin, and
      1.2% for penicillin V. The amoxicillin/clavulanate data were analyzed according
      to formulation: pooled-average. The incidence of ADD was 24.6% for the 4:1
      formulation, 12.8% for the 7:1 formulation, 19.0% for the 8:1 formulation, and
      20.2% for the 14:1 formulation. CONCLUSIONS: These results demonstrate
      substantially increased incidence of AAD following use of
      amoxicillin/clavulanate, compared to use of amoxicillin and penicillin V, as well
      as varying AAD rates with diffierent amoxicillin/clavulanate formulations. These
      findings warrant consideration when prescribing. The underlying mechanisms of AAD
      in children remain unclear.

PMID- 25964727
TI  - Injectable dexamethasone sodium phosphate administered orally? A pharmacokinetic
      analysis of a common emergency department practice.
AB  - BACKGROUND: The injectable formulation of dexamethasone has been administered
      orally, for the treatment of pediatric asthma and croup. The practice is followed
      in emergency departments around the country, but pharmacokinetic data supporting
      this practice are lacking. OBJECTIVES: This study evaluated the relative
      bioavailability and pharmacokinetics of dexamethasone sodium phosphate for
      injection (DSPI) administered orally compared to dexamethasone oral concentrate
      (DOC) in healthy adults. METHODS: This was an open label, crossover study of 11
      healthy adults 18 to 45 years of age. All subjects received 8 mg of dexamethasone
      oral concentrate initially. After a 1-week wash-out period, subjects received 8
      mg of DSPI administered orally. Dexamethasone levels were measured by liquid
      chromatography in tandem mass spectrometry. Cmax and area under the curve (AUC (0
      t) and AUC (0-infinity)) were calculated and compared between groups using the
      paired t test. RESULTS: The mean +/- SD AUC(0-t) for dexamethasone oral
      concentrate and DSPI were 5497.23 +/- 1649 and 4807.82 +/- 1971) ng/dL/hr,
      respectively; 90% confidence interval (CI) was 78.8%-96.9%. The mean +/- SD AUC(0
      infinity) for dexamethasone oral concentrate and DSPI were 6136.43 +/- 2577 and
      5591.48 +/- 3075 ng/dL/hr, respectively; 90% CI was 79.0% -105.2%. Mean Cmax +/-
      SD for DOC and DSPI were 942.94 +/- 151 and 790.92 +/- 229 ng/dL, respectively;
      90% CI 76.8%-91.7%. The relative bioavailability of DSPI administered orally was
      87.4% when using AUC(0-t) and 91.1% when using AUC(0-infinity). The calculated
      absolute bioavailability was 75.9%. CONCLUSIONS: DSPI is not bioequivalent to
      dexamethasone oral concentrate when administered orally. The existing literature
      supports the efficacy of DSPI despite this. Dosing adjustments may be considered.

PMID- 25964728
TI  - Characterization of dexmedetomidine dosing and safety in neonates and infants.
AB  - OBJECTIVES: To describe and compare off-label use and cardiovascular (CV) adverse
      effects of dexmedetomidine in neonates and infants in the pediatric intensive
      care unit (PICU). METHODS: Patients younger than 12 months with corrected
      gestational ages of at least 37 weeks who were receiving continuous infusion of
      dexmedetomidine at a tertiary pediatric referral center between October 2007 and
      August 2012 were assessed retrospectively. Patients were excluded if
      dexmedetomidine was used for procedural sedation, postoperative CV surgery, or if
      postanesthesia infusion weaning orders existed at the time of PICU admission.
      RESULTS: The median minimum dexmedetomidine dose was similar between infants and
      neonates at 0.2 mcg/kg/hr (IQR, 0.17-0.3) versus 0.29 mcg/kg/hr (IQR, 0.2-0.31),
      p = 0.35. The median maximum dose was higher for infants than neonates (0.6
      mcg/kg/hr [IQR, 0.4-0.8] vs. 0.4 mcg/kg/hr [IQR, 0.26-0.6], p < 0.01). Additional
      sedative use was more common in infants than neonates (75/99 [76%] vs. 15/28
      [54%], p = 0.02). At least 1 episode of hypotension was noted in 34/127 (27%)
      patients and was similar between groups. An episode of bradycardia was identified
      more frequently in infants than neonates (55/99 [56%] vs. 2/28 [7%], p < 0.01).
      Significant reduction in heart rate and systolic blood pressure was noted when
      comparing baseline vital signs to lowest heart rate and systolic blood pressure
      during infusion (p < 0.01). CONCLUSIONS: Dexmedetomidine dose ranges were similar
      to US Food and Drug Administration-labeled dosages for intensive care unit
      sedation in adults. More infants than neonates experienced a bradycardia episode,
      but infants were also more likely to receive higher dosages of dexmedetomidine
      and additional sedatives.

PMID- 25964729
TI  - Extended-interval gentamicin dosing in achieving therapeutic concentrations in
      malaysian neonates.
AB  - OBJECTIVE: To evaluate the usefulness of extended-interval gentamicin dosing
      practiced in neonatal intensive care unit (NICU) and special care nursery (SCN)
      of a Malaysian hospital. METHODS: Cross-sectional observational study with
      pharmacokinetic analysis of all patients aged <=28 days who received gentamicin
      treatment in NICU/SCN. Subjects received dosing according to a regimen modified
      from an Australian-based pediatric guideline. During a study period of 3 months,
      subjects were evaluated for gestational age, body weight, serum creatinine
      concentration, gentamicin dose/interval, serum peak and trough concentrations,
      and pharmacokinetic parameters. Descriptive percentages were used to determine
      the overall dosing accuracy, while analysis of variance (ANOVA) was conducted to
      compare the accuracy rates among different gestational ages. Pharmacokinetic
      profile among different gestational age and body weight groups were compared by
      using ANOVA. RESULTS: Of the 113 subjects included, 82.3% (n = 93) achieved
      therapeutic concentrations at the first drug-monitoring assessment. There was no
      significant difference found between the percentage of term neonates who achieved
      therapeutic concentrations and the premature group (87.1% vs. 74.4%), p = 0.085.
      A total of 112 subjects (99.1%) achieved desired therapeutic trough concentration
      of <2 mg/L. Mean gentamicin peak concentration was 8.52 mg/L (95% confidence
      interval [Cl], 8.13-8.90 mg/L) and trough concentration was 0.54 mg/L (95% CI,
      0.48-0.60 mg/L). Mean volume of distribution, half-life, and elimination rate
      were 0.65 L/kg (95% CI, 0.62-0.68 L/kg), 6.96 hours (95% CI, 6.52-7.40 hours),
      and 0.11 hour(-1) (95% CI, 0.10-0.11 hour(-1)), respectively. CONCLUSION: The
      larger percentage of subjects attaining therapeutic range with extended-interval
      gentamicin dosing suggests that this regimen is appropriate and can be safely
      used among Malaysian neonates.

PMID- 25964730
TI  - Retrospective analysis of large-dose intrapleural alteplase for complicated
      pediatric parapneumonic effusion and empyema.
AB  - OBJECTIVES: Medical treatment of complicated parapneumonic effusion or empyema in
      pediatric patients includes antibiotics and pleural space drainage. Intrapleural
      fibrinolysis may facilitate pleural drainage; however, there is a lack of
      consensus regarding the optimal dosing regimen. The primary purpose of this study
      was to evaluate the efficacy and safety of a large-dose intrapleural alteplase
      regimen in pediatric patients. Secondarily, this investigation sought to
      differentiate the clinical characteristics of responders and non-responders to
      intrapleural alteplase therapy. METHODS: All patients with parapneumonic
      effusions treated with intrapleural alteplase between June 2003 and December 2011
      were reviewed retrospectively. Efficacy was assessed by comparing chest tube
      output, in mL/hr and mL/kg/hr, for 24 hours before and after the first dose of
      alteplase. Additional efficacy outcomes included duration of in situ chest tubes,
      a need for surgical intervention for pleural effusion, and length of hospital
      stay. Safety was assessed by frequency and severity of adverse events. Non
      responders and responders were compared based on demographic and disease
      characteristics. Responders were defined as patients who did not require surgical
      intervention after intrapleural alteplase therapy. RESULTS: Seventy-three
      patients, aged 0.5 to 22.5 years, received intrapleural alteplase to facilitate
      pleural drainage. Median alteplase dose was 7 mg (range, 3 to 10 mg; median 0.38
      mg/kg). Chest tube output increased from 10.7 to 24.2 mL/hr (p = 0.006), and
      median length of hospital stay was 9 days. Eighty-four percent of patients were
      responders. The most common adverse events were pain (20.5%) and oxygen
      desaturation greater than 10% from baseline (16.4%). High-flow nasal cannula was
      the most common intervention for oxygen desaturation to 80% to 90%. Nine patients
      (12%) required a blood transfusion during the study. CONCLUSION: Large-dose
      intrapleural alteplase is effective in facilitating pleural drainage in pediatric
      patients with complicated parapneumonic effusion or empyema. Common adverse
      effects include pain and oxygen desaturation. The potential for bleeding warrants
      clinical monitoring.

PMID- 25964731
TI  - Metabolic and hormonal effects of antenatal betamethasone after 35 weeks of
      gestation.
AB  - BACKGROUND: Antenatal corticosteroid therapy recently has been considered for
      term and near-term infants, in addition to preterm infants, delivered by elective
      cesarean section, with the aim of preventing an adverse respiratory outcome.
      OBJECTIVES: The objective of this study was to investigate hormonal and metabolic
      effects of antenatal betamethasone when administered to term fetuses. METHODS:
      Cord blood levels of cortisol, C-peptide, insulin-like growth factor I and its
      binding protein 3, and 5 more analytes including glucose were measured in
      singleton newborns of over 35 weeks of gestational age. In anticipation of a
      cesarean delivery, the mother was either treated or not treated with 12 mg of
      intramuscularly administered antenatal betamethasone approximately 24 hours prior
      to birth. Babies of comparable gestational age, sex, and nutritional status who
      were not treated antenatally served as controls. RESULTS: Cord serum cortisol
      levels of the betamethasone-treated fetuses were suppressed to <10% of that of
      untreated controls (median levels of 11.6 nmol/L vs. 138.2 nmol/L, respectively),
      and their C-peptide and glucose levels were significantly higher (2.85 mcg/L vs.
      1.19 mcg/L, respectively, p < 0.0001; and 62.5 mg/dL vs. 56.0 mg/dL,
      respectively, p = 0.01). CONCLUSIONS: Prophylactic betamethasone therapy causes
      immediate hormonal alterations, which might interfere with the metabolic
      adaptation of the newborn. This issue deserves thorough investigation.

PMID- 25964732
TI  - MMR Vaccine: When Is the Right Time for the Second Dose?
AB  - Outbreaks of measles have been reported over the past 5 years, particularly
      affecting children between the ages of 1 and 5 years. Most of these children are
      younger than the age recommended by the Advisory Committee on Immunization
      Practices for the second dose of measles-mumps-rubella (MMR) vaccine. Question
      may arise as to whether strict adherence to the scheduled second dose is required
      or whether there is opportunity for earlier immunization under special
      circumstances (e.g., traveling abroad, poor response as evidenced by titer
      levels). The history of measles, its characteristics, and its evolving past and
      current immunization policies will be reviewed, focusing on the original intent
      of the recommended schedule and presenting a case in which deviating from current
      practice could be justified. 

PMID- 25964734
TI  - Pediatric news.

PMID- 25964733
TI  - Drug shortages and implications for pediatric patients.
AB  - Drug shortages in the United States continue to be a significant problem that
      negatively impacts pediatric patients of all ages. These shortages have been
      associated with a higher rate of relapse among children with cancer, substitution
      of less effective agents, and greater risk for short- and long-term toxicity.
      Effective prevention and management of any drug shortage must include
      considerations for issues specific to pediatric patients; hence, the Pediatric
      Pharmacy Advocacy Group (PPAG) strongly supports the effective management of
      shortages by institutions caring for pediatric patients. Recommendations
      published by groups such as the American Society of Health-System Pharmacists and
      the American Society for Parenteral and Enteral Nutrition should be incorporated
      into drug shortage management policies. PPAG also supports the efforts of the
      Food and Drug Administration (FDA) to not only address but prevent drug shortages
      caused by manufacturing and quality problems, delays in production, and
      discontinuations. Prevention, mitigation, and effective management of drug
      shortages pose significant challenges that require effective communication;
      hence, PPAG encourages enhanced and early dialogue between the FDA,
      pharmaceutical manufacturers, professional organizations, and health care
      institutions. 

PMID- 25964735
TI  - Cellular dynamics of neuronal migration in the hippocampus.
AB  - A fine structure of the hippocampus is required for proper functions, and
      disruption of this formation by neuronal migration defects during development may
      play a role in some psychiatric illnesses. During hippocampal development in
      rodents, pyramidal neurons in the Ammon's horn are mostly generated in the
      ventricular zone (VZ), spent as multipolar cells just above the VZ, and then
      migrate radially toward the pial surface, ultimately settling into the
      hippocampal plate. Although this process is similar to that of neocortical
      projection neurons, these are not identical. In addition to numerous histological
      studies, the development of novel techniques gives a clear picture of the
      cellular dynamics of hippocampal neurons, as well as neocortical neurons. In this
      article, we provide an overview of the cellular mechanisms of rodent hippocampal
      neuronal migration including those of dentate granule cells, especially focusing
      on the differences of migration modes between hippocampal neurons and neocortical
      neurons. The unique migration mode of hippocampal pyramidal neurons might enable
      clonally related cells in the Ammon's horn to distribute in a horizontal fashion.

PMID- 25964736
TI  - Classic and Golli Myelin Basic Protein have distinct developmental trajectories
      in human visual cortex.
AB  - Traditionally, myelin is viewed as insulation around axons, however, more recent
      studies have shown it also plays an important role in plasticity, axonal
      metabolism, and neuroimmune signaling. Myelin is a complex multi-protein
      structure composed of hundreds of proteins, with Myelin Basic Protein (MBP) being
      the most studied. MBP has two families: Classic-MBP that is necessary for
      activity driven compaction of myelin around axons, and Golli-MBP that is found in
      neurons, oligodendrocytes, and T-cells. Furthermore, Golli-MBP has been called a
      "molecular link" between the nervous and immune systems. In visual cortex
      specifically, myelin proteins interact with immune processes to affect experience
      dependent plasticity. We studied myelin in human visual cortex using Western
      blotting to quantify Classic- and Golli-MBP expression in post-mortem tissue
      samples ranging in age from 20 days to 80 years. We found that Classic- and Golli
      MBP have different patterns of change across the lifespan. Classic-MBP gradually
      increases to 42 years and then declines into aging. Golli-MBP has early
      developmental changes that are coincident with milestones in visual system
      sensitive period, and gradually increases into aging. There are three stages in
      the balance between Classic- and Golli-MBP expression, with Golli-MBP dominating
      early, then shifting to Classic-MBP, and back to Golli-MBP in aging. Also Golli
      MBP has a wave of high inter-individual variability during childhood. These
      results about cortical MBP expression are timely because they compliment recent
      advances in MRI techniques that produce high resolution maps of cortical myelin
      in normal and diseased brain. In addition, the unique pattern of Golli-MBP
      expression across the lifespan suggests that it supports high levels of
      neuroimmune interaction in cortical development and in aging. 

PMID- 25964737
TI  - Ancient interaction between the teneurin C-terminal associated peptides (TCAP)
      and latrophilin ligand-receptor coupling: a role in behavior.
AB  - Teneurins are multifunctional transmembrane proteins that are found in all
      multicellular animals and exist as four paralogous forms in vertebrates. They are
      highly expressed in the central nervous system, where they exert their effects,
      in part, by high-affinity binding to latrophilin (LPHN), a G-protein coupled
      receptor (GPCR) related to the adhesion and secretin GPCR families. The teneurin
      C-terminal associated peptides (TCAPs) are encoded by the terminal exon of all
      four teneurins, where TCAPs 1 and 3 are independently transcribed as soluble
      peptides, and TCAPs 2 and 4 remain tethered to their teneurin proprotein.
      Synthetic TCAP-1 interacts with LPHN, with an association with beta-dystroglycan,
      to induce a tissue-dependent signal cascade to modulate cytoskeletal dynamics.
      TCAP-1 reduces stress-induced behaviors associated with anxiety, addiction and
      depression in a variety of models, in part, by regulating synaptic plasticity.
      Therefore, the TCAP-1-teneurin-LPHN interaction represents a novel receptor
      ligand model and may represent a key mechanism underlying the association of
      behavior and neurological conditions. 

PMID- 25964738
TI  - Comparative performance of a genetically-encoded voltage indicator and a blue
      voltage sensitive dye for large scale cortical voltage imaging.
AB  - Traditional small molecule voltage sensitive dye indicators have been a powerful
      tool for monitoring large scale dynamics of neuronal activities but have several
      limitations including the lack of cell class specific targeting, invasiveness and
      difficulties in conducting longitudinal studies. Recent advances in the
      development of genetically-encoded voltage indicators have successfully overcome
      these limitations. Genetically-encoded voltage indicators (GEVIs) provide
      sufficient sensitivity to map cortical representations of sensory information and
      spontaneous network activities across cortical areas and different brain states.
      In this study, we directly compared the performance of a prototypic GEVI,
      VSFP2.3, with that of a widely used small molecule voltage sensitive dye (VSD),
      RH1691, in terms of their ability to resolve mesoscopic scale cortical population
      responses. We used three synchronized CCD cameras to simultaneously record the
      dual emission ratiometric fluorescence signal from VSFP2.3 and RH1691
      fluorescence. The results show that VSFP2.3 offers more stable and less invasive
      recording conditions, while the signal-to-noise level and the response dynamics
      to sensory inputs are comparable to RH1691 recordings. 

PMID- 25964739
TI  - Stim and Orai proteins in neuronal Ca(2+) signaling and excitability.
AB  - Stim1 and Orai1 are ubiquitous proteins that have long been known to mediate
      Ca(2+) release-activated Ca(2+) (CRAC) current (ICRAC) and store-operated Ca(2+)
      entry (SOCE) only in non-excitable cells. SOCE is activated following the
      depletion of the endogenous Ca(2+) stores, which are mainly located within the
      endoplasmic reticulum (ER), to replete the intracellular Ca(2+) reservoir and
      engage specific Ca(2+)-dependent processes, such as proliferation, migration,
      cytoskeletal remodeling, and gene expression. Their paralogs, Stim2, Orai2 and
      Orai3, support SOCE in heterologous expression systems, but their physiological
      role is still obscure. Ca(2+) inflow in neurons has long been exclusively
      ascribed to voltage-operated and receptor-operated channels. Nevertheless, recent
      work has unveiled that Stim1-2 and Orai1-2, but not Orai3, proteins are also
      expressed and mediate SOCE in neurons. Herein, we survey current knowledge about
      the neuronal distribution of Stim and Orai proteins in rodent and human brains;
      we further discuss that Orai2 is the main pore-forming subunit of CRAC channels
      in central neurons, in which it may be activated by either Stim1 or Stim2
      depending on species, brain region and physiological stimuli. We examine the
      functions regulated by SOCE in neurons, where this pathway is activated under
      resting conditions to refill the ER, control spinogenesis and regulate gene
      transcription. Besides, we highlighted the possibility that SOCE also controls
      neuronal excitation and regulate synaptic plasticity. Finally, we evaluate the
      involvement of Stim and Orai proteins in severe neurodegenerative and
      neurological disorders, such as Alzheimer's disease and epilepsy. 

PMID- 25964740
TI  - Role of adenosine in oligodendrocyte precursor maturation.
AB  - Differentiation and maturation of oligodendroglial cells are postnatal processes
      that involve specific morphological changes correlated with the expression of
      stage-specific surface antigens and functional voltage-gated ion channels. A
      small fraction of oligodendrocyte progenitor cells (OPCs) generated during
      development are maintained in an immature and slowly proliferative or quiescent
      state in the adult central nervous system (CNS) representing an endogenous
      reservoir of immature cells. Adenosine receptors are expressed by OPCs and a key
      role of adenosine in oligodendrocyte maturation has been recently recognized. As
      evaluated on OPC cultures, adenosine, by stimulating A1 receptors, promotes
      oligodendrocyte maturation and inhibits their proliferation; on the contrary, by
      stimulating A2A receptors, it inhibits oligodendrocyte maturation. A1 and A2A
      receptor-mediated effects are related to opposite modifications of outward
      delayed rectifying membrane K(+) currents (IK) that are involved in the
      regulation of oligodendrocyte differentiation. Brain A1 and A2A receptors might
      represent new molecular targets for drugs useful in demyelinating pathologies,
      such as multiple sclerosis (MS), stroke and brain trauma. 

PMID- 25964742
TI  - The methyl-CpG-binding domain (MBD) is crucial for MeCP2's dysfunction-induced
      defects in adult newborn neurons.
AB  - Mutations in the human X-linked gene MECP2 are responsible for most Rett syndrome
      (RTT) cases, predominantly within its methyl-CpG-binding domain (MBD). To examine
      the role of MBD in the pathogenesis of RTT, we generated two MeCP2 mutant
      constructs, one with a deletion of MBD (MeCP2-DeltaMBD), another mimicking a
      mutation of threonine 158 within the MBD (MeCP2-T158M) found in RTT patients.
      MeCP2 knockdown resulted in a decrease in total dendrite length, branching,
      synapse number, as well as altered spontaneous Ca(2+) oscillations in vitro,
      which could be reversed by expression of full length human MeCP2 (hMeCP2-FL).
      However, the expression of hMeCP2-DeltaMBD in MeCP2-silenced neurons did not
      rescue the changes in neuronal morphology and spontaneous Ca(2+) oscillations,
      while expression of hMeCP2-T158M in these neurons could only rescue the decrease
      in dendrite length and branch number. In vivo over expression of hMeCP2-FL but
      not hMeCP2-DeltaMBD in adult newborn neurons of the dentate gyrus also rescued
      the cell autonomous effect caused by MeCP2 deficiency in dendrites length and
      branching. Our results demonstrate that an intact and functional MBD is crucial
      for MeCP2 functions in cultured hippocampal neurons and adult newborn neurons. 

PMID- 25964743
TI  - Parcellation of the primary cerebral cortices based on local connectivity
      profiles.
AB  - Connectivity-based parcellation using diffusion MRI has been extensively used to
      parcellate subcortical areas and the association cortex. Connectivity profiles
      are vital for connectivity-based parcellation. Two categories of connectivity
      profiles are generally utilized, including global connectivity profiles, in which
      the connectivity information is from the seed to the whole brain, and long
      connectivity profiles, in which the connectivity information is from the seed to
      other brain regions after excluding the seed. However, whether global or long
      connectivity profiles should be applied in parcellating the primary cortex
      utilizing connectivity-based parcellation is unclear. Many sources of evidence
      have indicated that the primary cerebral cortices are composed of structurally
      and functionally distinct subregions. Because the primary cerebral cortices are
      rich in local anatomic hierarchical connections and possess high degree of local
      functional connectivity profiles, we proposed that local connectivity profiles,
      that is the connectivity information within a seed region of interest, might be
      used for parcellating the primary cerebral cortices. In this study, the global,
      long, and local connectivity profiles were separately used to parcellate the
      bilateral M1, A1, S1, and V1. We found that results using the three profiles were
      all quite consistent with reported cytoarchitectonic evidence. More importantly,
      the results using local connectivity profiles showed less inter-subject
      variability than the results using the other two, a finding which suggests that
      local connectivity profiles are superior to global and long connectivity profiles
      for parcellating the primary cerebral cortices. This also implies that, depending
      on the characteristics of specific areas of the cerebral cortex, different
      connectivity profiles may need to be adopted to parcellate different areas. 

PMID- 25964741
TI  - ClC-1 chloride channels: state-of-the-art research and future challenges.
AB  - The voltage-dependent ClC-1 chloride channel belongs to the CLC
      channel/transporter family. It is a homodimer comprising two individual pores
      which can operate independently or simultaneously according to two gating modes,
      the fast and the slow gate of the channel. ClC-1 is preferentially expressed in
      the skeletal muscle fibers where the presence of an efficient Cl(-) homeostasis
      is crucial for the correct membrane repolarization and propagation of action
      potential. As a consequence, mutations in the CLCN1 gene cause dominant and
      recessive forms of myotonia congenita (MC), a rare skeletal muscle channelopathy
      caused by abnormal membrane excitation, and clinically characterized by muscle
      stiffness and various degrees of transitory weakness. Elucidation of the
      mechanistic link between the genetic defects and the disease pathogenesis is
      still incomplete and, at this time, there is no specific treatment for MC. Still
      controversial is the subcellular localization pattern of ClC-1 channels in
      skeletal muscle as well as its modulation by some intracellular factors. The
      expression of ClC-1 in other tissues such as in brain and heart and the possible
      assembly of ClC-1/ClC-2 heterodimers further expand the physiological properties
      of ClC-1 and its involvement in diseases. A recent de novo CLCN1 truncation
      mutation in a patient with generalized epilepsy indeed postulates an unexpected
      role of this channel in the control of neuronal network excitability. This review
      summarizes the most relevant and state-of-the-art research on ClC-1 chloride
      channels physiology and associated diseases. 

PMID- 25964744
TI  - Behavioral detection of intra-cortical microstimulation in the primary and
      secondary auditory cortex of cats.
AB  - Although neural responses to sound stimuli have been thoroughly investigated in
      various areas of the auditory cortex, the results electrophysiological recordings
      cannot establish a causal link between neural activation and brain function.
      Electrical microstimulation, which can selectively perturb neural activity in
      specific parts of the nervous system, is an important tool for exploring the
      organization and function of brain circuitry. To date, the studies describing the
      behavioral effects of electrical stimulation have largely been conducted in the
      primary auditory cortex. In this study, to investigate the potential differences
      in the effects of electrical stimulation on different cortical areas, we measured
      the behavioral performance of cats in detecting intra-cortical microstimulation
      (ICMS) delivered in the primary and secondary auditory fields (A1 and A2,
      respectively). After being trained to perform a Go/No-Go task cued by sounds, we
      found that cats could also learn to perform the task cued by ICMS; furthermore,
      the detection of the ICMS was similarly sensitive in A1 and A2. Presenting
      wideband noise together with ICMS substantially decreased the performance of cats
      in detecting ICMS in A1 and A2, consistent with a noise masking effect on the
      sensation elicited by the ICMS. In contrast, presenting ICMS with pure-tones in
      the spectral receptive field of the electrode-implanted cortical site reduced
      ICMS detection performance in A1 but not A2. Therefore, activation of A1 and A2
      neurons may produce different qualities of sensation. Overall, our study revealed
      that ICMS-induced neural activity could be easily integrated into an animal's
      behavioral decision process and had an implication for the development of
      cortical auditory prosthetics. 

PMID- 25964745
TI  - Qualitative assessment of patients' attitudes and expectations toward BCIs and
      implications for future technology development.
AB  - Brain-computer-interfaces (BCIs) are important for the next generation of neuro
      prosthesis innovations. Only few pilot projects have tested patients' abilities
      to control BCIs as well as their satisfaction with the offered technologies. On
      the one hand, little is known about patients' moral attitudes toward the benefit
      risk-ratio of BCIs as well as their needs, priorities, and expectations. On the
      other hand, ethics experts intensively discuss the general risks of BCIs as well
      as the limits of neuro-enhancement. To our knowledge, we present here the first
      qualitative interview study with ten chronic patients matching the potential user
      categories for motor and communication BCIs to assess their practical and moral
      attitudes toward this technology. The interviews reveal practical and moral
      attitudes toward motor BCIs that can impact future technology development. We
      discuss our empirical findings on patients' perspectives and compare them to
      neuroscientists' and ethicists' perspectives. Our analysis indicates only partial
      overlap between the potential users' and the experts' assessments of BCI
      technology. It points out the importance of considering the needs and desires of
      the targeted patient group. Based on our findings, we suggest a multi-fold
      approach to the development of clinical BCIs, rooted in the participatory
      technology-development. We conclude that clinical BCI development needs to be
      explored in a disease-related and culturally sensitive way. 

PMID- 25964746
TI  - Application of radiosurgical techniques to produce a primate model of brain
      lesions.
AB  - Behavioral analysis of subjects with discrete brain lesions provides important
      information about the mechanisms of various brain functions. However, it is
      generally difficult to experimentally produce discrete lesions in deep brain
      structures. Here we show that a radiosurgical technique, which is used as an
      alternative treatment for brain tumors and vascular malformations, is applicable
      to create non-invasive lesions in experimental animals for the research in
      systems neuroscience. We delivered highly focused radiation (130-150 Gy at ISO
      center) to the frontal eye field (FEF) of macaque monkeys using a clinical linear
      accelerator (LINAC). The effects of irradiation were assessed by analyzing
      oculomotor performance along with magnetic resonance (MR) images before and up to
      8 months following irradiation. In parallel with tissue edema indicated by MR
      images, deficits in saccadic and smooth pursuit eye movements were observed
      during several days following irradiation. Although initial signs of oculomotor
      deficits disappeared within a month, damage to the tissue and impaired eye
      movements gradually developed during the course of the subsequent 6 months.
      Postmortem histological examinations showed necrosis and hemorrhages within a
      large area of the white matter and, to a lesser extent, in the adjacent gray
      matter, which was centered at the irradiated target. These results indicated that
      the LINAC system was useful for making brain lesions in experimental animals,
      while the suitable radiation parameters to generate more focused lesions need to
      be further explored. We propose the use of a radiosurgical technique for
      establishing animal models of brain lesions, and discuss the possible uses of
      this technique for functional neurosurgical treatments in humans. 

PMID- 25964748
TI  - Understanding public (mis)understanding of tDCS for enhancement.
AB  - In order to gain insight into the public's perspective on using the minimally
      invasive technique transcranial direct current stimulation (tDCS) as an
      enhancement tool, we analyzed and compared online comments in key popular press
      articles from two different periods (pre-commercialization and post
      commercialization). The main conclusion drawn from this exploratory investigation
      is that public perception regarding tDCS has shifted from misunderstanding to
      cautionary realism. This change in attitude can be explained as moving from a
      focus on an emergent technology to a focus on its applications, benefits, and
      risks as the technology becomes more grounded within the public domain. Future
      governance of tDCS should include the concerns and enthusiasms of the public. 

PMID- 25964747
TI  - Neurons in red nucleus and primary motor cortex exhibit similar responses to
      mechanical perturbations applied to the upper-limb during posture.
AB  - Primary motor cortex (M1) and red nucleus (RN) are brain regions involved in limb
      motor control. Both structures are highly interconnected with the cerebellum and
      project directly to the spinal cord, although the contribution of RN is smaller
      than M1. It remains uncertain whether RN and M1 serve similar or distinct roles
      during posture and movement. Many neurons in M1 respond rapidly to mechanical
      disturbances of the limb, but it remains unclear whether RN neurons also respond
      to such limb perturbations. We have compared discharges of single neurons in RN
      (n = 49) and M1 (n = 109) of one monkey during a postural perturbation task.
      Neural responses to whole-limb perturbations were examined by transiently
      applying (300 ms) flexor or extensor torques to the shoulder and/or elbow while
      the monkeys attempted to maintain a static hand posture. Relative to baseline
      discharges before perturbation onset, perturbations evoked rapid (<100 ms)
      changes of neural discharges in many RN (28 of 49, 57%) and M1 (43 of 109, 39%)
      neurons. In addition to exhibiting a greater proportion of perturbation-related
      neurons, RN neurons also tended to exhibit higher peak discharge frequencies in
      response to perturbations than M1 neurons. Importantly, neurons in both
      structures exhibited similar response latencies and tuning properties (preferred
      torque directions and tuning widths) in joint-torque space. Proximal arm muscles
      also displayed similar tuning properties in joint-torque space. These results
      suggest that RN is more sensitive than M1 to mechanical perturbations applied
      during postural control but both structures may play a similar role in feedback
      control of posture. 

PMID- 25964749
TI  - Differences in long-term memory stability and AmCREB level between forward and
      backward conditioned honeybees (Apis mellifera).
AB  - In classical conditioning a predictive relationship between a neutral stimulus
      (conditioned stimulus; CS) and a meaningful stimulus (unconditioned stimulus; US)
      is learned when the CS precedes the US. In backward conditioning the sequence of
      the stimuli is reversed. In this situation animals might learn that the CS
      signals the end or the absence of the US. In honeybees 30 min and 24 h following
      backward conditioning a memory for the excitatory and inhibitory properties of
      the CS could be retrieved, but it remains unclear whether a late long-term memory
      is formed that can be retrieved 72 h following backward conditioning. Here we
      examine this question by studying late long-term memory formation in forward and
      backward conditioning of the proboscis extension response (PER). We report a
      difference in the stability of memory formed upon forward and backward
      conditioning with the same number of conditioning trials. We demonstrate a
      transcription-dependent memory 72 h after forward conditioning but do not observe
      a 72 h memory after backward conditioning. Moreover we find that protein
      degradation is differentially involved in memory formation following these two
      conditioning protocols. We report differences in the level of a transcription
      factor, the cAMP response element binding protein (CREB) known to induce
      transcription underlying long-term memory formation, following forward and
      backward conditioning. Our results suggest that these alterations in CREB levels
      might be regulated by the proteasome. We propose that the differences observed
      are due to the sequence of stimulus presentation between forward and backward
      conditioning and not to differences in the strength of the association of both
      stimuli. 

PMID- 25964750
TI  - Early life environmental and pharmacological stressors result in persistent
      dysregulations of the serotonergic system.
AB  - Dysregulations in the brain serotonergic system and exposure to environmental
      stressors have been implicated in the development of major depressive disorder.
      Here, we investigate the interactions between the stress and serotonergic systems
      by characterizing the behavioral and biochemical effects of chronic stress
      applied during early-life or adulthood in wild type (WT) mice and mice with
      deficient tryptophan hydroxylase 2 (TPH2) function. We showed that chronic mild
      stress applied in adulthood did not affect the behaviors and serotonin levels of
      WT and TPH2 knock-in (KI) mice. Whereas, maternal separation (MS) stress
      increased anxiety- and depressive-like behaviors of WT mice, with no detectable
      behavioral changes in TPH2 KI mice. Biochemically, we found that MS WT mice had
      reduced brain serotonin levels, which was attributed to increased expression of
      monoamine oxidase A (MAO A). The increased MAO A expression was detected in MS WT
      mice at 4 weeks old and adulthood. No change in TPH2 expression was detected. To
      determine whether a pharmacological stressor, dexamethasone (Dex), will result in
      similar biochemical results obtained from MS, we used an in vitro system, SH-SY5Y
      cells, and found that Dex treatment resulted in increased MAO A expression
      levels. We then treated WT mice with Dex for 5 days, either during postnatal days
      7-11 or adulthood. Both groups of Dex treated WT mice had reduced basal
      corticosterone and glucocorticoid receptors expression levels. However, only Dex
      treatment during PND7-11 resulted in reduced serotonin levels and increased MAO A
      expression. Just as with MS WT mice, TPH2 expression in PND7-11 Dex-treated WT
      mice was unaffected. Taken together, our findings suggest that both environmental
      and pharmacological stressors affect the expression of MAO A, and not TPH2, when
      applied during the critical postnatal period. This leads to long-lasting
      perturbations in the serotonergic system, and results in anxiety- and depressive
      like behaviors. 

PMID- 25964751
TI  - Stimulus onset predictability modulates proactive action control in a Go/No-go
      task.
AB  - The aim of the study was to evaluate whether the presence/absence of visual cues
      specifying the onset of an upcoming, action-related stimulus modulates pre
      stimulus brain activity, associated with the proactive control of goal-directed
      actions. To this aim we asked 12 subjects to perform an equal probability Go/No
      go task with four stimulus configurations in two conditions: (1) uncued, i.e.,
      without any external information about the timing of stimulus onset; and (2)
      cued, i.e., with external visual cues providing precise information about the
      timing of stimulus onset. During task both behavioral performance and event
      related potentials (ERPs) were recorded. Behavioral results showed faster
      response times in the cued than uncued condition, confirming existing literature.
      ERPs showed novel results in the proactive control stage, that started about 1 s
      before the motor response. We observed a slow rising prefrontal positive
      activity, more pronounced in the cued than the uncued condition. Further, also
      pre-stimulus activity of premotor areas was larger in cued than uncued condition.
      In the post-stimulus period, the P3 amplitude was enhanced when the time of
      stimulus onset was externally driven, confirming that external cueing enhances
      processing of stimulus evaluation and response monitoring. Our results suggest
      that different pre-stimulus processing come into play in the two conditions. We
      hypothesize that the large prefrontal and premotor activities recorded with
      external visual cues index the monitoring of the external stimuli in order to
      finely regulate the action. 

PMID- 25964752
TI  - Linking appraisal to behavioral flexibility in animals: implications for stress
      research.
AB  - In fluctuating environments, organisms require mechanisms enabling the rapid
      expression of context-dependent behaviors. Here, we approach behavioral
      flexibility from a perspective rooted in appraisal theory, aiming to provide a
      better understanding on how animals adjust their internal state to environmental
      context. Appraisal has been defined as a multi-component and interactive process
      between the individual and the environment, in which the individual must evaluate
      the significance of a stimulus to generate an adaptive response. Within this
      framework, we review and reframe the existing evidence for the appraisal
      components in animal literature, in an attempt to reveal the common ground of
      appraisal mechanisms between species. Furthermore, cognitive biases may occur in
      the appraisal of ambiguous stimuli. These biases may be interpreted either as
      states open to environmental modulation or as long-lasting phenotypic traits.
      Finally, we discuss the implications of cognitive bias for stress research. 

PMID- 25964753
TI  - DTI measures track and predict motor function outcomes in stroke rehabilitation
      utilizing BCI technology.
AB  - Tracking and predicting motor outcomes is important in determining effective
      stroke rehabilitation strategies. Diffusion tensor imaging (DTI) allows for
      evaluation of the underlying structural integrity of brain white matter tracts
      and may serve as a potential biomarker for tracking and predicting motor
      recovery. In this study, we examined the longitudinal relationship between DTI
      measures of the posterior limb of the internal capsule (PLIC) and upper-limb
      motor outcomes in 13 stroke patients (median 20-month post-stroke) who completed
      up to 15 sessions of intervention using brain-computer interface (BCI)
      technology. Patients' upper-limb motor outcomes and PLIC DTI measures including
      fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and
      mean diffusivity (MD) were assessed longitudinally at four time points: pre-, mid
      , immediately post- and 1-month-post intervention. DTI measures and ratios of
      each DTI measure comparing the ipsilesional and contralesional PLIC were
      correlated with patients' motor outcomes to examine the relationship between
      structural integrity of the PLIC and patients' motor recovery. We found that
      lower diffusivity and higher FA values of the ipsilesional PLIC were
      significantly correlated with better upper-limb motor function. Baseline DTI
      ratios were significantly correlated with motor outcomes measured immediately
      post and 1-month-post BCI interventions. A few patients achieved improvements in
      motor recovery meeting the minimum clinically important difference (MCID). These
      findings suggest that upper-limb motor recovery in stroke patients receiving BCI
      interventions relates to the microstructural status of the PLIC. Lower
      diffusivity and higher FA measures of the ipsilesional PLIC contribute toward
      better motor recovery in the stroke-affected upper-limb. DTI-derived measures may
      be a clinically useful biomarker in tracking and predicting motor recovery in
      stroke patients receiving BCI interventions. 

PMID- 25964754
TI  - The implications of age-related neurofunctional compensatory mechanisms in
      executive function and language processing including the new Temporal Hypothesis
      for Compensation.
AB  - As the passage of time structurally alters one's brain, cognition does not have
      to suffer the same faith, at least not to the same extent. Indeed, the existence
      of age-related compensatory mechanisms allow for some cognitive preservation.
      This paper attempts to coherently review the existing concepts of neurofunctional
      compensation when applied to two different cognitive domains, namely executive
      function and language processing. More precisely, we explore the Cognitive
      reserve (CR) model in healthy aging as well as its two underlying mechanisms:
      neural reserve and neural compensation. Furthermore, we review the Compensation
      Related Utilization of Neural Circuits Hypothesis as well as the Growing Of Life
      Differences Explains Normal Aging model. Finally, we propose, based on some
      functional neuroimaging studies, the existence of another compensatory mechanism
      characterized by age-related delayed cerebral activation allowing for cognitive
      performance to be preserved at the expense of speed processing: the Temporal
      Hypothesis for Compensation. 

PMID- 25964755
TI  - How can we study reasoning in the brain?
AB  - The brain did not develop a dedicated device for reasoning. This fact bears
      dramatic consequences. While for perceptuo-motor functions neural activity is
      shaped by the input's statistical properties, and processing is carried out at
      high speed in hardwired spatially segregated modules, in reasoning, neural
      activity is driven by internal dynamics and processing times, stages, and
      functional brain geometry are largely unconstrained a priori. Here, it is shown
      that the complex properties of spontaneous activity, which can be ignored in a
      short-lived event-related world, become prominent at the long time scales of
      certain forms of reasoning. It is argued that the neural correlates of reasoning
      should in fact be defined in terms of non-trivial generic properties of
      spontaneous brain activity, and that this implies resorting to concepts,
      analytical tools, and ways of designing experiments that are as yet non-standard
      in cognitive neuroscience. The implications in terms of models of brain activity,
      shape of the neural correlates, methods of data analysis, observability of the
      phenomenon, and experimental designs are discussed. 

PMID- 25964756
TI  - Stochastic non-linear oscillator models of EEG: the Alzheimer's disease case.
AB  - In this article, the Electroencephalography (EEG) signal of the human brain is
      modeled as the output of stochastic non-linear coupled oscillator networks. It is
      shown that EEG signals recorded under different brain states in healthy as well
      as Alzheimer's disease (AD) patients may be understood as distinct, statistically
      significant realizations of the model. EEG signals recorded during resting eyes
      open (EO) and eyes-closed (EC) resting conditions in a pilot study with AD
      patients and age-matched healthy control subjects (CTL) are employed. An
      optimization scheme is then utilized to match the output of the stochastic
      Duffing-van der Pol double oscillator network with EEG signals recorded during
      each condition for AD and CTL subjects by selecting the model physical parameters
      and noise intensity. The selected signal characteristics are power spectral
      densities in major brain frequency bands Shannon and sample entropies. These
      measures allow matching of linear time varying frequency content as well as non
      linear signal information content and complexity. The main finding of the work is
      that statistically significant unique models represent the EC and EO conditions
      for both CTL and AD subjects. However, it is also shown that the inclusion of
      sample entropy in the optimization process, to match the complexity of the EEG
      signal, enhances the stochastic non-linear oscillator model performance. 

PMID- 25964757
TI  - Reproducibility of neuroimaging analyses across operating systems.
AB  - Neuroimaging pipelines are known to generate different results depending on the
      computing platform where they are compiled and executed. We quantify these
      differences for brain tissue classification, fMRI analysis, and cortical
      thickness (CT) extraction, using three of the main neuroimaging packages (FSL,
      Freesurfer and CIVET) and different versions of GNU/Linux. We also identify some
      causes of these differences using library and system call interception. We find
      that these packages use mathematical functions based on single-precision floating
      point arithmetic whose implementations in operating systems continue to evolve.
      While these differences have little or no impact on simple analysis pipelines
      such as brain extraction and cortical tissue classification, their accumulation
      creates important differences in longer pipelines such as subcortical tissue
      classification, fMRI analysis, and cortical thickness extraction. With FSL, most
      Dice coefficients between subcortical classifications obtained on different
      operating systems remain above 0.9, but values as low as 0.59 are observed.
      Independent component analyses (ICA) of fMRI data differ between operating
      systems in one third of the tested subjects, due to differences in motion
      correction. With Freesurfer and CIVET, in some brain regions we find an effect of
      build or operating system on cortical thickness. A first step to correct these
      reproducibility issues would be to use more precise representations of floating
      point numbers in the critical sections of the pipelines. The numerical stability
      of pipelines should also be reviewed. 

PMID- 25964758
TI  - Computerized spatial delayed recognition span task: a specific tool to assess
      visuospatial working memory.
AB  - A new tablet device version (IOS platform) of the Spatial Delayed Recognition
      Span Task (SDRST) was developed with the aim of investigating visuospatial
      Working Memory (WM) abilities based on touchscreen technology. This new WM
      testing application will be available to download for free in Apple Store app
      ("SDRST app"). In order to verify the feasibility of this computer-based task, we
      conducted three experiments with different manipulations and groups of
      participants. We were interested in investigating if (1) the SDRST is sensitive
      enough to tap into cognitive differences brought by aging and dementia; (2)
      different experimental manipulations work successfully; (3) cortical brain
      activations seen in other WM tasks are also demonstrated here; and (4) non-human
      primates are able to answer the task. Performance (scores and response time) was
      better for young than older adults and higher for the latter when compared to
      Alzheimer's disease (AD) patients. All groups performed better with facial
      stimuli than with images of scenes and with emotional than with neutral stimuli.
      Electrophysiology data showed activation on prefrontal and frontal areas of
      scalp, theta band activity on the midline area, and gamma activity in left
      temporal area. There are all scalp regions known to be related to attention and
      WM. Besides those data, our sample of adult captive capuchin monkeys (Sapajus
      libidinosus) answered the task above chance level. Taken together, these results
      corroborate the reliability of this new computer-based SDRST as a measure of
      visuospatial WM in clinical and non-clinical populations as well as in non-human
      primates. Its tablet app allows the task to be administered in a wide range of
      settings, including hospitals, homes, schools, laboratories, universities, and
      research institutions. 

PMID- 25964761
TI  - After all, plasmalemmal expression of type-1 VDAC can be understood.
      Phosphorylation, nitrosylation, and channel modulators work together in
      vertebrate cell volume regulation and either apoptotic pathway.

PMID- 25964760
TI  - Role of transporters in the distribution of platinum-based drugs.
AB  - Platinum derivatives used as chemotherapeutic drugs such as cisplatin and
      oxaliplatin have a potent antitumor activity. However, severe side effects such
      as nephro-, oto-, and neurotoxicity are associated with their use. Effects and
      side effects of platinum-based drugs are in part caused by their transporter
      mediated uptake in target and non target cells. In this mini review, the
      transport systems involved in cellular handling of platinum derivatives are
      illustrated, focusing on transporters for cisplatin. The copper transporter 1
      seems to be of particular importance for cisplatin uptake in tumor cells, while
      the organic cation transporter (OCT) 2, due to its specific organ distribution,
      may play a major role in the development of undesired cisplatin side effects. In
      polarized cells, e.g., in renal proximal tubule cells, apically expressed
      transporters, such as multidrug and toxin extrusion protein 1, mediate secretion
      of cisplatin and in this way contribute to the control of its toxic effects.
      Specific inhibition of cisplatin uptake transporters such as the OCTs may be an
      attractive therapeutic option to reduce its toxicity, without impairing its
      antitumor efficacy. 

PMID- 25964759
TI  - Heme oxygenase and the immune system in normal and pathological pregnancies.
AB  - Normal pregnancy is an immunotolerant state. Many factors, including
      environmental, socioeconomic, genetic, and immunologic changes by infection
      and/or other causes of inflammation, may contribute to inter-individual
      differences resulting in a normal or pathologic pregnancy. In particular,
      imbalances in the immune system can cause many pregnancy-related diseases, such
      as infertility, abortions, pre-eclampsia, and preterm labor, which result in
      maternal/fetal death, prematurity, or small-for-gestational age newborns. New
      findings imply that myeloid regulatory cells and regulatory T cells (Tregs) may
      mediate immunotolerance during normal pregnancy. Effector T cells (Teffs) have,
      in contrast, been implicated to cause adverse pregnancy outcomes. Furthermore,
      feto-maternal tolerance affects the developing fetus. It has been shown that the
      Treg/Teff balance affects litter size and adoptive transfer of pregnancy-induced
      Tregs can prevent fetal rejection in the mouse. Heme oxygenase-1 (HO-1) has a
      protective role in many conditions through its anti-inflammatory, anti-apoptotic,
      antioxidative, and anti-proliferative actions. HO-1 is highly expressed in the
      placenta and plays a role in angiogenesis and placental vascular development and
      in regulating vascular tone in pregnancy. In addition, HO-1 is a major regulator
      of immune homeostasis by mediating crosstalk between innate and adaptive immune
      systems. Moreover, HO-1 can inhibit inflammation-induced phenotypic maturation of
      immune effector cells and pro-inflammatory cytokine secretion and promote anti
      inflammatory cytokine production. HO-1 may also be associated with T-cell
      activation and can limit immune-based tissue injury by promoting Treg suppression
      of effector responses. Thus, HO-1 and its byproducts may protect against
      pregnancy complications by its immunomodulatory effects, and the regulation of HO
      1 or its downstream effects has the potential to prevent or treat pregnancy
      complications and prematurity. 

PMID- 25964762
TI  - Specificity and context in post-exercise recovery: it is not a one-size-fits-all
      approach.

PMID- 25964764
TI  - The role of personal self-regulation and regulatory teaching to predict
      motivational-affective variables, achievement, and satisfaction: a structural
      model.
AB  - The present investigation examines how personal self-regulation (presage
      variable) and regulatory teaching (process variable of teaching) relate to
      learning approaches, strategies for coping with stress, and self-regulated
      learning (process variables of learning) and, finally, how they relate to
      performance and satisfaction with the learning process (product variables). The
      objective was to clarify the associative and predictive relations between these
      variables, as contextualized in two different models that use the presage-process
      product paradigm (the Biggs and DEDEPRO models). A total of 1101 university
      students participated in the study. The design was cross-sectional and
      retrospective with attributional (or selection) variables, using correlations and
      structural analysis. The results provide consistent and significant empirical
      evidence for the relationships hypothesized, incorporating variables that are
      part of and influence the teaching-learning process in Higher Education. Findings
      confirm the importance of interactive relationships within the teaching-learning
      process, where personal self-regulation is assumed to take place in connection
      with regulatory teaching. Variables that are involved in the relationships
      validated here reinforce the idea that both personal factors and teaching and
      learning factors should be taken into consideration when dealing with a formal
      teaching-learning context at university. 

PMID- 25964765
TI  - On the gender-science stereotypes held by scientists: explicit accord with gender
      ratios, implicit accord with scientific identity.
AB  - Women's representation in science has changed substantially, but unevenly, over
      the past 40 years. In health and biological sciences, for example, women's
      representation among U.S. scientists is now on par with or greater than men's,
      while in physical sciences and engineering they remain a clear minority. We
      investigated whether variation in proportions of women in scientific disciplines
      is related to differing levels of male-favoring explicit or implicit stereotypes
      held by students and scientists in each discipline. We hypothesized that science
      is-male stereotypes would be weaker in disciplines where women are better
      represented. This prediction was tested with a sample of 176,935 college-educated
      participants (70% female), including thousands of engineers, physicians, and
      scientists. The prediction was supported for the explicit stereotype, but not for
      the implicit stereotype. Implicit stereotype strength did not correspond with
      disciplines' gender ratios, but, rather, correlated with two indicators of
      disciplines' scientific intensity, positively for men and negatively for women.
      From age 18 on, women who majored or worked in disciplines perceived as more
      scientific had substantially weaker science-is-male stereotypes than did men in
      the same disciplines, with gender differences larger than 0.8 standard deviations
      in the most scientifically-perceived disciplines. Further, particularly for
      women, differences in the strength of implicit stereotypes across scientific
      disciplines corresponded with the strength of scientific values held by women in
      the disciplines. These results are discussed in the context of dual process
      theory of mental operation and balanced identity theory. The findings point to
      the need for longitudinal study of the factors' affecting development of adults'
      and, especially, children's implicit gender stereotypes and scientific identity. 

PMID- 25964763
TI  - Functional and structural remodeling of glutamate synapses in prefrontal and
      frontal cortex induced by behavioral stress.
AB  - Increasing evidence has shown that the pathophysiology of neuropsychiatric
      disorders, including mood disorders, is associated with abnormal function and
      regulation of the glutamatergic system. Consistently, preclinical studies on
      stress-based animal models of pathology showed that glucocorticoids and stress
      exert crucial effects on neuronal excitability and function, especially in
      cortical and limbic areas. In prefrontal and frontal cortex, acute stress was
      shown to induce enhancement of glutamate release/transmission dependent on
      activation of corticosterone receptors. Although the mechanisms whereby stress
      affects glutamate transmission have not yet been fully understood, it was shown
      that synaptic, non-genomic action of corticosterone is required to increase the
      readily releasable pool of glutamate vesicles, but is not sufficient to enhance
      transmission in prefrontal and frontal cortex. Slower, partly genomic mechanisms
      are probably necessary for the enhancement of glutamate transmission induced by
      stress. Combined evidence has suggested that the changes in glutamate release and
      transmission are responsible for the dendritic remodeling and morphological
      changes induced by stress and it has been argued that sustained alterations of
      glutamate transmission may play a key role in the long-term structural/functional
      changes associated with mood disorders in patients. Intriguingly, modifications
      of the glutamatergic system induced by stress in the prefrontal cortex seem to be
      biphasic. Indeed, while the fast response to stress suggests an enhancement in
      the number of excitatory synapses, synaptic transmission and working memory, long
      term adaptive changes - including those consequent to chronic stress - induce
      opposite effects. Better knowledge of the cellular effectors involved in this
      biphasic effect of stress may be useful to understand the pathophysiology of
      stress-related disorders, and open new paths for the development of therapeutic
      approaches. 

PMID- 25964766
TI  - When "AA" is long but "A" is not short: speakers who distinguish short and long
      vowels in production do not necessarily encode a short-long contrast in their
      phonological lexicon.
AB  - In some languages (such as Dutch), speakers produce duration differences between
      vowels, but it is unclear whether they also encode short versus long speech
      sounds into different phonological categories. To examine whether they have
      abstract representations for 'short' versus 'long' contrasts, we assessed Dutch
      listeners' perceptual sensitivity to duration in two vowel qualities: [a] and
      [alpha], as in the words maan 'moon' and man 'man,' which are realized with long
      and short duration respectively. If Dutch represents this phonetic durational
      difference as a 'short'-'long' contrast in its phonology, duration changes in [a]
      and [alpha] should elicit similar neural responses [specifically, the mismatch
      negativity (MMN)]. However, we found that duration changes evoked larger MMN
      amplitude for [a] than for [alpha]. This finding indicates that duration is
      phonemically relevant for the maan-vowel that is represented as 'long,' while it
      is not phonemically specified for the man-vowel. We argue that speakers who in
      speech production distinguish a given vowel pair on the basis of duration may not
      necessarily encode this durational distinction as a binary 'short'-'long'
      contrast in their phonological lexicon. 

PMID- 25964767
TI  - Assessing anger regulation in middle childhood: development and validation of a
      behavioral observation measure.
AB  - An observational measure of anger regulation in middle childhood was developed
      that facilitated the in situ assessment of five maladaptive regulation strategies
      in response to an anger-eliciting task. 599 children aged 6-10 years (M = 8.12,
      SD = 0.92) participated in the study. Construct validity of the measure was
      examined through correlations with parent- and self-reports of anger regulation
      and anger reactivity. Criterion validity was established through links with
      teacher-rated aggression and social rejection measured by parent-, teacher-, and
      self-reports. The observational measure correlated significantly with parent- and
      self-reports of anger reactivity, whereas it was unrelated to parent- and self
      reports of anger regulation. It also made a unique contribution to predicting
      aggression and social rejection. 

PMID- 25964768
TI  - Coaching to vision versus coaching to improvement needs: a preliminary
      investigation on the differential impacts of fostering positive and negative
      emotion during real time executive coaching sessions.
AB  - Drawing on intentional change theory (ICT; Boyatzis, 2006), this study examined
      the differential impact of inducing coaching recipients' vision/positive emotion
      versus improvement needs/negative emotion during real time executive coaching
      sessions. A core aim of the study was to empirically test two central ICT
      propositions on the effects of using the coached person's Positive Emotional
      Attractor (vision/PEA) versus Negative Emotional Attractor (improvement
      needs/NEA) as the anchoring framework of a onetime, one-on-one coaching session
      on appraisal of 360 degrees  feedback and discussion of possible change goals.
      Eighteen coaching recipients were randomly assigned to two coaching conditions,
      the coaching to vision/PEA condition and the coaching to improvement needs/NEA
      condition. Two main hypotheses were tested. Hypothesis1 predicted that
      participants in the vision/PEA condition would show higher levels of expressed
      positive emotion during appraisal of 360 degrees  feedback results and discussion
      of change goals than recipients in the improvement needs/NEA condition.
      Hypothesis2 predicted that vision/PEA participants would show lower levels of
      stress immediately after the coaching session than improvement needs/NEA
      participants. Findings showed that coaching to vision/the PEA fostered
      significantly lower levels of expressed negative emotion and anger during
      appraisal of 360 degrees  feedback results as compared to coaching to
      improvements needs/the NEA. Vision-focused coaching also fostered significantly
      greater exploration of personal passions and future desires, and more positive
      engagement during 360 degrees  feedback appraisal. No significant differences
      between the two conditions were found in emotional processing during discussion
      of change goals or levels of stress immediately after the coaching session.
      Current findings suggest that vision/PEA arousal versus improvement needs/NEA
      arousal impact the coaching process in quite different ways; that the coach's
      initial framing of the session predominantly in the PEA (or, alternatively,
      predominantly in the NEA) fosters emotional processing that is driven by this
      initial framing; and that both the PEA (and associated positive emotions) and NEA
      (and associated negative emotions) play an important and recurrent role in
      shaping the change process. Further study on these outcomes will enable
      researchers to shed more light on the differential impact of the PEA versus NEA
      on intentional change, and how to leverage the benefits of both emotional
      attractors. Findings also suggest that coaches can benefit from better
      understanding the importance of tapping intrinsic motivation and personal
      passions through coaching to vision/the PEA. Coaches additionally may benefit
      from better understanding how to leverage the long-term advantages, and
      restorative benefits, of positive emotions during coaching engagements. The
      findings also highlight coaches' need to appreciate the impact of timing effects
      on coaching intentional change, and how coaches can play a critical role in
      calibrating the pace and focus of work on intentional change. Early arousal of
      the coachee's PEA, accompanied by recurrent PEA-NEA induction, may help coachees
      be/become more creative, optimistic, and resilient during a given change process.
      Overall, primary focus on vision/PEA and secondary focus on improvement needs/NEA
      may better equip coaches and coaching recipients to work together on building
      robust learning, development, and change. Keywords-133pt executive coaching,
      vision, improvement needs, positive emotion, negative emotion, emotional
      appraisal, intentional change, positive psychology. 

PMID- 25964769
TI  - Probabilistic alternatives to Bayesianism: the case of explanationism.
AB  - There has been a probabilistic turn in contemporary cognitive science. Far and
      away, most of the work in this vein is Bayesian, at least in name. Coinciding
      with this development, philosophers have increasingly promoted Bayesianism as the
      best normative account of how humans ought to reason. In this paper, we make a
      push for exploring the probabilistic terrain outside of Bayesianism. Non
      Bayesian, but still probabilistic, theories provide plausible competitors both to
      descriptive and normative Bayesian accounts. We argue for this general idea via
      recent work on explanationist models of updating, which are fundamentally
      probabilistic but assign a substantial, non-Bayesian role to explanatory
      considerations. 

PMID- 25964770
TI  - A new biomarker to examine the role of hippocampal function in the development of
      spatial reorientation in children: a review.
AB  - Spatial navigation is an adaptive skill that involves determining the route to a
      particular goal or location, and then traveling that path. A major component of
      spatial navigation is spatial reorientation, or the ability to reestablish a
      sense of direction after being disoriented. The hippocampus is known to be
      critical for navigating, and has more recently been implicated in reorienting in
      adults, but relatively little is known about the development of the hippocampus
      in relation to these large-scale spatial abilities in children. It has been
      established that, compared to school-aged children, preschool children tend to
      perform poorly on certain spatial reorientation tasks, suggesting that their
      hippocampi may not be mature enough to process the demands of such a task.
      Currently, common techniques used to examine underlying brain activity, such as
      electroencephalography (EEG) and functional magnetic resonance imaging (fMRI),
      are not suitable for examining hippocampal development in young children. In the
      present paper, we argue instead for the use of eyeblink conditioning (EBC), a
      relatively under-utilized, inexpensive, and safe method that is easy to implement
      in developing populations. In addition, EBC has a well defined neural circuitry,
      which includes the hippocampus, making it an ideal tool to indirectly measure
      hippocampal functioning in young children. In this review, we will evaluate the
      literature on EBC and its relation to hippocampal development, and discuss the
      possibility of using EBC as an objective measure of associative learning in
      relation to large-scale spatial skills. We support the use of EBC as a way to
      indirectly access hippocampal function in typical and atypical populations in
      order to characterize the neural substrates associated with the development of
      spatial reorientation abilities in early childhood. As such, EBC is a potential,
      simple biomarker for success in tasks that require the hippocampus, including
      spatial reorientation. 

PMID- 25964771
TI  - Turning the hands of time again: a purely confirmatory replication study and a
      Bayesian analysis.
AB  - In a series of four experiments, Topolinski and Sparenberg (2012) found support
      for the conjecture that clockwise movements induce psychological states of
      temporal progression and an orientation toward the future and novelty. Here we
      report the results of a preregistered replication attempt of Experiment 2 from
      Topolinski and Sparenberg (2012). Participants turned kitchen rolls either
      clockwise or counterclockwise while answering items from a questionnaire
      assessing openness to experience. Data from 102 participants showed that the
      effect went slightly in the direction opposite to that predicted by Topolinski
      and Sparenberg (2012), and a preregistered Bayes factor hypothesis test revealed
      that the data were 10.76 times more likely under the null hypothesis than under
      the alternative hypothesis. Our findings illustrate the theoretical importance
      and practical advantages of preregistered Bayes factor replication studies, both
      for psychological science and for empirical work in general. 

PMID- 25964772
TI  - Dutch and English toddlers' use of linguistic cues in predicting upcoming turn
      transitions.
AB  - Adults achieve successful coordination during conversation by using prosodic and
      lexicosyntactic cues to predict upcoming changes in speakership. We examined the
      relative weight of these linguistic cues in the prediction of upcoming turn
      structure by toddlers learning Dutch (Experiment 1; N = 21) and British English
      (Experiment 2; N = 20) and adult control participants (Dutch: N = 16; English: N
      = 20). We tracked participants' anticipatory eye movements as they watched videos
      of dyadic puppet conversation. We controlled the prosodic and lexicosyntactic
      cues to turn completion for a subset of the utterances in each conversation to
      create four types of target utterances (fully incomplete, incomplete syntax,
      incomplete prosody, and fully complete). All participants (Dutch and English
      toddlers and adults) used both prosodic and lexicosyntactic cues to anticipate
      upcoming speaker changes, but weighed lexicosyntactic cues over prosodic ones
      when the two were pitted against each other. The results suggest that Dutch and
      English toddlers are already nearly adult-like in their use of prosodic and
      lexicosyntactic cues in anticipating upcoming turn transitions. 

PMID- 25964773
TI  - Relations among questionnaire and experience sampling measures of inner speech: a
      smartphone app study.
AB  - Inner speech is often reported to be a common and central part of inner
      experience, but its true prevalence is unclear. Many questionnaire-based measures
      appear to lack convergent validity and it has been claimed that they overestimate
      inner speech in comparison to experience sampling methods (which involve
      collecting data at random timepoints). The present study compared self-reporting
      of inner speech collected via a general questionnaire and experience sampling,
      using data from a custom-made smartphone app (Inner Life). Fifty-one university
      students completed a generalized self-report measure of inner speech (the
      Varieties of Inner Speech Questionnaire, VISQ) and responded to at least seven
      random alerts to report on incidences of inner speech over a 2-week period.
      Correlations and pairwise comparisons were used to compare generalized
      endorsements and randomly sampled scores for each VISQ subscale. Significant
      correlations were observed between general and randomly sampled measures for only
      two of the four VISQ subscales, and endorsements of inner speech with evaluative
      or motivational characteristics did not correlate at all across different
      measures. Endorsement of inner speech items was significantly lower for random
      sampling compared to generalized self-report, for all VISQ subscales. Exploratory
      analysis indicated that specific inner speech characteristics were also related
      to anxiety and future-oriented thinking. 

PMID- 25964774
TI  - Temporal perception in visual processing as a research tool.
AB  - Accumulated evidence has shown that the subjective time in the sub-second range
      can be altered by different factors; some are related to stimulus features such
      as luminance contrast and spatial frequency, others are processes like perceptual
      grouping and contextual modulation. These findings indicate that temporal
      perception uses neural signals involved in non-temporal feature processes and
      that perceptual organization plays an important role in shaping the experience of
      elapsed time. We suggest that the temporal representation of objects can be
      treated as a feature of objects. This new concept implies that psychological time
      can serve as a tool to study the principles of neural codes in the perception of
      objects like "reaction time (RT)." Whereas "RT" usually reflects the state of
      transient signals crossing decision thresholds, "apparent time" in addition
      reveals the dynamics of sustained signals, thus providing complementary
      information of what has been obtained from "RT" studies. 

PMID- 25964775
TI  - Follow-Up Imaging: Molecular Imaging is Likely Best as a Single Modality, but
      Multimodality Imaging is the Future.

PMID- 25964776
TI  - Adipose tissue dysfunction and impaired metabolic health in human obesity: a
      matter of oxygen?

PMID- 25964778
TI  - Sexual Dimorphism in Glucose and Lipid Metabolism during Fasting, Hypoglycemia,
      and Exercise.
AB  - Sexually dimorphic physiologic responses occur during fasting, hypoglycemia, and
      exercise. The areas covered in this mini review include studies that have used
      isotopic tracer methods and/or euglycemic clamp studies to investigate substrate
      metabolism during the above common physiologic stress. Women have greater
      reliance on lipid metabolism during fasting, hypoglycemia, and exercise while men
      exhibit preference of carbohydrate utilization. Plasma glucose concentrations
      were shown to be lower, while free fatty acids (FFA) and lipolysis higher in
      women compared to men after fasting. Hypoglycemia resulted in significantly
      reduced epinephrine, norepinephrine, glucagon, growth hormone, pancreatic
      polypeptide, and hepatic glucose production responses in females as compared to
      males. Sexual dimorphism during exercise was demonstrated by higher glycerol and
      FFA responses in women compared to men and higher carbohydrate oxidation rate in
      men. Mechanisms that can increase lipolytic rates in women include higher total
      fat mass, enhanced lipolytic sensitivity to epinephrine, and increased activation
      of beta adrenergic receptors. 

PMID- 25964777
TI  - Role of IGF1R in Breast Cancer Subtypes, Stemness, and Lineage Differentiation.
AB  - Insulin-like growth factor (IGF) signaling is fundamental for growth and
      survival. A large body of evidence (laboratory, epidemiological, and clinical)
      implicates the exploitation of this pathway in cancer. Up to 50% of breast tumors
      express the activated form of the type 1 insulin-like growth factor receptor
      (IGF1R). Breast cancers are categorized into subtypes based upon hormone and
      ERRB2 receptor expression and/or gene expression profiling. Even though IGF1R
      influences tumorigenic phenotypes and drug resistance across all breast cancer
      subtypes, it has specific expression and function in each. In some subtypes,
      IGF1R levels correlate with a favorable prognosis, while in others it is
      associated with recurrence and poor prognosis, suggesting different actions based
      upon cellular and molecular contexts. In this review, we examine IGF1R expression
      and function as it relates to breast cancer subtype and therapy-acquired
      resistance. Additionally, we discuss the role of IGF1R in stem cell maintenance
      and lineage differentiation and how these cell fate influences may alter the
      differentiation potential and cellular composition of breast tumors. 

PMID- 25964779
TI  - Targeting the IGF-1R: The Tale of the Tortoise and the Hare.
AB  - The insulin-like growth factor type 1 receptor (IGF-1R) plays a key role in the
      development and maintenance of cancer. Since the first links between growth
      factor receptors and oncogenes were noted over three decades ago, targeting the
      IGF-1R has been of great interest. This review follows the progress from
      inception through intense pharmaceutical development, disappointing clinical
      trials and recent updates to the signaling paradigm. In light of major
      developments in signaling understanding and activation complexities, we examine
      reasons for failure of first line targeting approaches. Recent findings include
      the fact that the IGF-1R can signal in the absence of the ligand, in the absence
      of kinase activity, and utilizes components of the GPCR system. With recognition
      of the unappreciated complexities that this first wave of targeting approaches
      encountered, we advocate re-recognition of IGF-1R as a valid target for cancer
      treatment and look to future directions, where both research and pharmaceutical
      strengths can lend themselves to finally unearthing anti-IGF-1R potential. 

PMID- 25964780
TI  - Rv2031c of Mycobacterium tuberculosis: a master regulator of Rv2028-Rv2031 (HspX)
      operon.
AB  - Genes belonging to the same operon are transcribed as a single mRNA molecule in
      all prokaryotes. The genes of the same operon are presumed to be involved in
      similar metabolic and physiological processes. Hence, computational analysis of
      constituent proteins could provide important clues to the functional
      relationships within the operonic genes. This tends to be more fruitful in the
      case of Mycobacterium tuberculosis (Mtb), considering the number of hypothetical
      genes with unknown functions and interacting partners. Dramatic advances in the
      past decade have increased our knowledge of the mechanisms that tubercle bacilli
      employ to survive within the host. But the phenomenon of Mtb latency continues to
      baffle all. Rv2031c belonging to dormancy regulon of Mtb is predominantly
      expressed during latency, with myriad immunological roles. Thus we attempted to
      analyze the operon comprising Rv2031c protein to gain insights into its role
      during latency. In the current study, we have carried out computational analysis
      of proteins encoded by genes known to be a part of this operon. Our study
      includes phylogenetic analysis, modeling of protein 3D structures, and protein
      interaction network analysis. We describe the mechanistic role in the
      establishment of latency and regulation of DevS-DevR component system.
      Additionally, we have identified the probable role of these proteins in
      carbohydrate metabolism, erythromycin tolerance, and nucleotide synthesis. Hence,
      these proteins can modulate the metabolism of Mtb inside the host cells and can
      be important for its survival in latency. The functional characterization and
      interactome of this important operon can give insight into its role during
      latency along with the exploitation of constituent proteins as drug targets and
      vaccine candidates. 

PMID- 25964781
TI  - Perturbed states of the bacterial chromosome: a thymineless death case study.
AB  - Spatial patterns of transcriptional activity in the living genome of Escherichia
      coli represent one of the more peculiar aspects of the E. coli chromosome
      biology. Spatial transcriptional correlations can be observed throughout the
      chromosome, and their formation depends on the state of replication in the cell.
      The condition of thymine starvation leading to thymineless death (TLD) is at the
      "cross-roads" of replication and transcription. According to a current view,
      e.g., (Cagliero et al., 2014), one of the cellular objectives is to segregate the
      processes of transcription and replication in time and space. An ultimate
      segregation would take place when one process is inhibited and another is not, as
      it happens during thymine starvation, which results in numerous molecular and
      physiological abnormalities associated with TLD. One of such abnormalities is the
      loss of spatial correlations in the vicinity of the origin of replication. We
      review the transcriptional consequences of replication inhibition by thymine
      starvation in a context of the state of DNA template in the starved cells and
      opine about a possible significance of normal physiological coupling between the
      processes of replication and transcription. 

PMID- 25964782
TI  - A Clinical and Laboratory Approach to the Evaluation of Innate Immunity in
      Pediatric CVID Patients.
AB  - Defective adaptive immune responses are well studied in common variable
      immunodeficiency (CVID) patients; however, more focus is needed on innate immune
      system defects to explain CVID's clinical and laboratory heterogeneity. This is
      the first study comparing migratory function of granulocytes, oxidative burst
      activity of phagocytic cells, surface integrin expressions on neutrophils and
      lymphocytes, natural killer (NK) cell numbers and cytotoxic activity, natural
      killer T cells, lymphocyte subsets such as CD8(+)CD28(+), CD4(+)CTLA-4(+) cells
      in CVID patients (n: 20) and healthy controls (n: 26). The relationship between
      laboratory findings and some clinical was also investigated. CD3(+)CD8(+) T
      cytotoxic cells were found to be elevated in CVID patients, but
      CD3(+)CD8(+)CD28(+) or CD3(+)CD8(+)CD28(-) cells did not show any significant
      difference. CD4(+)CTLA-4(+) cell percentages were significantly lower in CVID
      patients compared to healthy controls. Severe CVID patients had decreased
      percentages of NK cells with increased NK cell cytotoxicity suggesting possibly
      increased activation. Furthermore, CD3(-)CD16(+)CD56(+)CD28(+) cells of CVID
      patients were elevated while percentage of CD28(-) NK cells was decreased.
      Neutrophil migration percentages were lower but and oxidative burst activity was
      not affected. CD11a expressions on these cells were depressed in contrast to
      increased expression of CD18. Innate immunity defects may affect the extent of
      recurrence and severity of infections in CVID. Our observations highlight some of
      these associations and indicate the need for further similar studies for
      improving better innate system evaluation batteries for these patients. Further
      phenotypic correlations of these analyses will help clinicians reach a more
      definitive target for the molecular genetic diagnostic of pediatric CVID
      patients. 

PMID- 25964785
TI  - Citrullination and carbamylation in the pathophysiology of rheumatoid arthritis.
AB  - The discovery that citrullination was crucial for the recognition of antigens by
      the most disease-specific class of autoantibodies in rheumatoid arthritis (RA)
      had a huge impact on studies aimed at understanding autoimmunity in this disease.
      In addition to the detailed characterization of anti-citrullinated protein
      antibodies, various studies have addressed the identity of citrullinated
      antigens. These investigations were facilitated by new methods to characterize
      these proteins, the analysis of protein citrullination by peptidylarginine
      deiminases, the generation of a catalog of citrullinated proteins present in the
      inflamed joints of patients and the finding that the formation of extracellular
      traps is dependent on the activity of peptidylarginine deiminase activity.
      Recently, it was found that in addition to citrullination also carbamylation,
      which results in chemically highly related modified proteins, yields antigens
      that are targeted by rheumatoid arthritis patient sera. Here, all of these
      aspects will be discussed, culminating in current ideas about the involvement of
      citrullination and carbamylation in pathophysiological processes in autoimmunity,
      especially RA. 

PMID- 25964784
TI  - Germinal center reaction following cutaneous dengue virus infection in immune
      competent mice.
AB  - Dengue virus (DENV) has four serotypes, which can cause from asymptomatic disease
      to severe dengue. Heterologous secondary infections have been associated to a
      greater risk of potentially fatal dengue due to non-neutralizing memory
      antibodies (Abs), which facilitate the infection, such as anti-precursor membrane
      (prM) Abs, among other mechanisms. Usually, class-switched memory Abs are
      generated mainly through germinal centers (GCs). However, the cellular events
      underlying these Ab responses to DENV, especially during repeated/secondary
      infections, have been poorly studied. We wanted to know whether there is
      involvement of GC reactions during cutaneous DENV infection and whether there is
      any sort of preferential Ab responses to defined viral proteins. Intradermal DENV
      inoculation at a relatively low dose efficiently infects immune-competent BALB/c
      mice, inducing higher quantities of DENV-specific GC B cells and larger GCs than
      the control conditions. Interestingly, GCs exhibited as much prM as envelope (E)
      and non-structural 3 viral proteins in situ. Intriguingly, despite the much
      larger abundance of E protein than of prM protein in the virions, infected
      animals showed similar amounts of circulating Abs and Ag-specific GC B cells both
      for prM and for E proteins, even significantly higher for prM. To the best of our
      knowledge, there are no reports of the GC responses during DENV infection. This
      relatively stronger anti-prM response could be triggered by DENV to
      preferentially promote Abs against certain viral proteins, which might favor
      infections by facilitating DENV invasion of host cells. It is thus conceivably
      that DENV might have evolved to induce this kind of Ab responses. 

PMID- 25964783
TI  - Combinatorial strategies for the induction of immunogenic cell death.
AB  - The term "immunogenic cell death" (ICD) is commonly employed to indicate a
      peculiar instance of regulated cell death (RCD) that engages the adaptive arm of
      the immune system. The inoculation of cancer cells undergoing ICD into
      immunocompetent animals elicits a specific immune response associated with the
      establishment of immunological memory. Only a few agents are intrinsically
      endowed with the ability to trigger ICD. These include a few chemotherapeutics
      that are routinely employed in the clinic, like doxorubicin, mitoxantrone,
      oxaliplatin, and cyclophosphamide, as well as some agents that have not yet been
      approved for use in humans. Accumulating clinical data indicate that the
      activation of adaptive immune responses against dying cancer cells is associated
      with improved disease outcome in patients affected by various neoplasms. Thus,
      novel therapeutic regimens that trigger ICD are urgently awaited. Here, we
      discuss current combinatorial approaches to convert otherwise non-immunogenic
      instances of RCD into bona fide ICD. 

PMID- 25964786
TI  - The Impact of Glycosyl-Phosphatidyl-Inositol Anchored MICA Alleles on Novel NKG2D
      Based Therapies.

PMID- 25964787
TI  - Recent advances on the development and regulation of flower color in ornamental
      plants.
AB  - Flower color is one of the most important features of ornamental plants. Its
      development and regulation are influenced by many internal and external factors.
      Therefore, understanding the mechanism of color development and its regulation
      provides an important theoretical basis and premise for the cultivation and
      improvement of new color varieties of ornamental plants. This paper outlines the
      functions of petal tissue structure, as well as the distribution and type of
      pigments, especially anthocyanins, in color development. The progress of research
      on flower color regulation with a focus on physical factors, chemical factors,
      and genetic engineering is introduced. The shortcomings of flower color research
      and the potential directions for future development are explored to provide a
      broad background for flower color improvements in ornamental plants. 

PMID- 25964788
TI  - Growth and physiological changes in continuously cropped eggplant (Solanum
      melongena L.) upon relay intercropping with garlic (Allium sativum L.).
AB  - Relay intercropping represents an alternative for sustainable production of
      vegetables, but the changes of internally antioxidant defense combined with the
      growth and yield are not clear. Field experiment was carried out to investigate
      the malondialdehyde (MDA) content and activity levels of superoxide dismutase
      (SOD), peroxidase (POD), polyphenol oxidase (PPO), and phenylalanine ammonia
      lyase (PAL) in eggplant (Solanum melongena L.) and plant height, stem diameter,
      maximal leaf area, and yield of eggplant grown under successive cropping in the
      year 2011 and 2012 to see if relay intercropping with garlic (Allium sativum L.)
      could benefit to eggplant growth and yield. Three experimental treatments with
      three repeats in each were carried out (completely randomized block design):
      eggplant monoculture (CK), eggplant relay intercropping with normal garlic (NG),
      and eggplant relay intercropping with green garlic (GG). In both years, the MDA
      content was significantly lower and SOD and POD activities were generally lower
      in NG and GG compared with CK in most sampling dates. PPO activity trends were
      generally opposite to those of POD. The general trend of PAL activity was similar
      to MDA. The plant height and stem of eggplant was lower, but the maximal leaf
      area was larger in NG and GG in 2011; in 2012 the plant growth was stronger in
      relay intercropping treatments. For eggplant yield in 2011, NG was 2.85% higher
      than CK; after the time for the green garlic pulled out was moved forward in
      2012, the yield was increased by 6.26 and 7.80%, respectively, in NG and GG. The
      lower MDA content and enzyme activities in relay intercropping treatments showed
      that the eggplant suffered less damage from environment and continuous cropping
      obstacles, which promoted healthier plant. Thus from both the growth and
      physiological perspective, it was concluded that eggplant/garlic relay
      intercropping is a beneficial cultivation practice maintaining stronger plant
      growth and higher yield. 

PMID- 25964790
TI  - Herbaceous plant species invading natural areas tend to have stronger adaptive
      root foraging than other naturalized species.
AB  - Although plastic root-foraging responses are thought to be adaptive, as they may
      optimize nutrient capture of plants, this has rarely been tested. We investigated
      whether nutrient-foraging responses are adaptive, and whether they pre-adapt
      alien species to become natural-area invaders. We grew 12 pairs of congeneric
      species (i.e., 24 species) native to Europe in heterogeneous and homogeneous
      nutrient environments, and compared their foraging responses and performance. One
      species in each pair is a USA natural-area invader, and the other one is not.
      Within species, individuals with strong foraging responses, measured as
      plasticity in root diameter and specific root length, had a higher biomass. Among
      species, the ones with strong foraging responses, measured as plasticity in root
      length and root biomass, had a higher biomass. Our results therefore suggest that
      root foraging is an adaptive trait. Invasive species showed significantly
      stronger root-foraging responses than non-invasive species when measured as root
      diameter. Biomass accumulation was decreased in the heterogeneous vs. the
      homogeneous environment. In aboveground, but not belowground and total biomass,
      this decrease was smaller in invasive than in non-invasive species. Our results
      show that strong plastic root-foraging responses are adaptive, and suggest that
      it might aid in pre-adapting species to becoming natural-area invaders. 

PMID- 25964789
TI  - Genetic and epigenetic control of plant heat responses.
AB  - Plants have evolved sophisticated genetic and epigenetic regulatory systems to
      respond quickly to unfavorable environmental conditions such as heat, cold,
      drought, and pathogen infections. In particular, heat greatly affects plant
      growth and development, immunity and circadian rhythm, and poses a serious threat
      to the global food supply. According to temperatures exposing, heat can be
      usually classified as warm ambient temperature (about 22-27 degrees C), high
      temperature (27-30 degrees C) and extremely high temperature (37-42 degrees C,
      also known as heat stress) for the model plant Arabidopsis thaliana. The genetic
      mechanisms of plant responses to heat have been well studied, mainly focusing on
      elevated ambient temperature-mediated morphological acclimation and acceleration
      of flowering, modulation of circadian clock and plant immunity by high
      temperatures, and thermotolerance to heat stress. Recently, great progress has
      been achieved on epigenetic regulation of heat responses, including DNA
      methylation, histone modifications, histone variants, ATP-dependent chromatin
      remodeling, histone chaperones, small RNAs, long non-coding RNAs and other
      undefined epigenetic mechanisms. These epigenetic modifications regulate the
      expression of heat-responsive genes and function to prevent heat-related damages.
      This review focuses on recent progresses regarding the genetic and epigenetic
      control of heat responses in plants, and pays more attention to the role of the
      major epigenetic mechanisms in plant heat responses. Further research
      perspectives are also discussed. 

PMID- 25964791
TI  - Satellite RNAs interfere with the function of viral RNA silencing suppressors.
AB  - Viral satellite RNAs (satRNAs) are small subviral RNAs and depend on the helper
      virus for replication and spread. satRNAs can attenuate helper virus-induced
      symptoms, the mechanism of which remains unclear. Here, we show that two virus
      encoded suppressors of RNA silencing (VSRs), Cucumber mosaic virus (CMV) 2b and
      Tombusvirus P19, suppress hairpin RNA (hpRNA)-induced silencing of a beta
      glucuronidase (GUS) gene in Nicotiana benthamiana. This suppression can be
      overcome by CMV Y-satellite RNA (Y-Sat) via the Y-Sat-derived small interfering
      RNAs (siRNAs), which bind to the VSRs and displace the bound hpGUS-derived
      siRNAs. We also show that microRNA target gene expression in N. tabacum was
      elevated by CMV infection, presumably due to function of the 2b VSR, but this
      upregulation of microRNA target genes was reversed in the presence of Y-Sat.
      These results suggest that satRNA infection minimizes the effect of VSRs on host
      siRNA and microRNA-directed silencing. Our results suggest that the high
      abundance of satRNA-derived siRNAs contributes to symptom attenuation by binding
      helper virus-encoded VSRs, minimizing the capacity of the VSRs to bind host siRNA
      and miRNA and interfere with their function. 

PMID- 25964792
TI  - The functions of the cytoskeleton and associated proteins during mitosis and
      cytokinesis in plant cells.
AB  - In higher plants, microtubule (MT)-based, and actin filament (AF)-based
      structures play important roles in mitosis and cytokinesis. Besides the mitotic
      spindle, the evolution of a band comprising cortical MTs and AFs, namely, the
      preprophase band (PPB), is evident in plant cells. This band forecasts a specific
      division plane before the initiation of mitosis. During cytokinesis, another
      plant-specific cytoskeletal structure called the phragmoplast guides vesicles in
      the creation of a new cell wall. In addition, a number of cytoskeleton-associated
      proteins are reportedly involved in the formation and function of the PPB,
      mitotic spindle, and phragmoplast. This review summarizes current knowledge on
      the cytoskeleton-associated proteins that mediate the cytoskeletal arrays during
      mitosis and cytokinesis in plant cells and discusses the interaction between MTs
      and AFs involved in mitosis and cytokinesis. 

PMID- 25964793
TI  - Cisgenic apple trees; development, characterization, and performance.
AB  - Two methods were developed for the generation of cisgenic apples. Both have been
      successfully applied producing trees. The first method avoids the use of any
      foreign selectable marker genes; only the gene-of-interest is integrated between
      the T-DNA border sequences. The second method makes use of recombinase-based
      marker excision. For the first method we used the MdMYB10 gene from a red-fleshed
      apple coding for a transcription factor involved in regulating anthocyanin
      biosynthesis. Red plantlets were obtained and presence of the cisgene was
      confirmed. Plantlets were grafted and grown in a greenhouse. After 3 years, the
      first flowers appeared, showing red petals. Pollination led to production of red
      fleshed cisgenic apples. The second method used the pM(arker)F(ree) vector
      system, introducing the scab resistance gene Rvi6, derived from apple.
      Agrobacterium-mediated transformation, followed by selection on kanamycin,
      produced genetically modified apple lines. Next, leaves from in vitro material
      were treated to activate the recombinase leading to excision of selection genes.
      Subsequently, the leaf explants were subjected to negative selection for marker
      free plantlets by inducing regeneration on medium containing 5-fluorocytosine.
      After verification of the marker-free nature, the obtained plants were grafted
      onto rootstocks. Young trees from four cisgenic lines and one intragenic line,
      all containing Rvi6, were planted in an orchard. Appropriate controls were
      incorporated in this trial. We scored scab incidence for three consecutive years
      on leaves after inoculations with Rvi6-avirulent strains. One cisgenic line and
      the intragenic line performed as well as the resistant control. In 2014 trees
      started to overcome their juvenile character and formed flowers and fruits. The
      first results of scoring scab symptoms on apple fruits were obtained. Apple
      fruits from susceptible controls showed scab symptoms, while fruits from cisgenic
      and intragenic lines were free of scab. 

PMID- 25964794
TI  - Plant architecture without multicellularity: quandaries over patterning and the
      soma-germline divide in siphonous algae.
AB  - Multicellularity has independently evolved numerous times throughout the major
      lineages of life. Often, multicellularity can enable complex, macroscopic
      organismal architectures but it is not required for the elaboration of
      morphology. Several alternative cellular strategies have arisen as solutions
      permitting exquisite forms. The green algae class Ulvophyceae, for example,
      contains truly multicellular organisms, as well as macroscopic siphonous cells
      harboring one or multiple nuclei, and siphonocladous species, which are
      multinucleate and multicellular. These diverse cellular organizations raise a
      number of questions about the evolutionary and molecular mechanisms underlying
      complex organismal morphology in the green plants. Importantly, how does
      morphological patterning arise in giant coenocytes, and do nuclei, analogous to
      cells in multicellular organisms, take on distinct somatic and germline
      identities? Here, we comparatively explore examples of patterning and
      differentiation in diverse coenocytic and single-cell organisms and discuss
      possible mechanisms of development and nuclear differentiation in the siphonous
      algae. 

PMID- 25964795
TI  - What makes Xanthomonas albilineans unique amongst xanthomonads?
AB  - Xanthomonas albilineans causes leaf scald, a lethal disease of sugarcane.
      Compared to other species of Xanthomonas, X. albilineans exhibits distinctive
      pathogenic mechanisms, ecology and taxonomy. Its genome, which has experienced
      significant erosion, has unique genomic features. It lacks two loci required for
      pathogenicity in other plant pathogenic species of Xanthomonas: the xanthan gum
      biosynthesis and the Hrp-T3SS (hypersensitive response and pathogenicity-type
      three secretion system) gene clusters. Instead, X. albilineans harbors in its
      genome an SPI-1 (Salmonella pathogenicity island-1) T3SS gene cluster usually
      found in animal pathogens. X. albilineans produces a potent DNA gyrase inhibitor
      called albicidin, which blocks chloroplast differentiation, resulting in the
      characteristic white foliar stripe symptoms. The antibacterial activity of
      albicidin also confers on X. albilineans a competitive advantage against rival
      bacteria during sugarcane colonization. Recent chemical studies have uncovered
      the unique structure of albicidin and allowed us to partially elucidate its
      fascinating biosynthesis apparatus, which involves an enigmatic hybrid PKS/NRPS
      (polyketide synthase/non-ribosomal peptide synthetase) machinery. 

PMID- 25964796
TI  - Trypanosomosis: potential driver of selection in African cattle.
AB  - Trypanosomosis is a serious cause of reduction in productivity of cattle in
      tsetse-fly infested areas. Baoule and other local Taurine cattle breeds in
      Burkina Faso are trypanotolerant. Zebuine cattle, which are also kept there are
      susceptible to trypanosomosis but bigger in body size. Farmers have continuously
      been intercrossing Baoule and Zebu animals to increase production and disease
      tolerance. The aim of this study was to compare levels of zebuine and taurine
      admixture in genomic regions potentially involved in trypanotolerance with
      background admixture of composites to identify differences in allelic frequencies
      of tolerant and non-tolerant animals. The study was conducted on 214 animals (90
      Baoule, 90 Zebu, and 34 composites), genotyped with 25 microsatellites across the
      genome and with 155 SNPs in 23 candidate regions. Degrees of admixture of
      composites were analyzed for microsatellite and SNP data separately. Average
      Baoule admixture based on microsatellites across the genomes of the Baoule- Zebu
      composites was 0.31, which was smaller than the average Baoule admixture in the
      trypanosomosis candidate regions of 0.37 (P = 0.15). Fixation index F ST measured
      in the overall genome based on microsatellites or with SNPs from candidate
      regions indicates strong differentiation between breeds. Nine out of 23 regions
      had F ST >= 0.20 calculated from haplotypes or individual SNPs. The levels of
      admixture were significantly different from background admixture, as revealed by
      microsatellite data, for six out of the nine regions. Five out of the six regions
      showed an excess of Baoule ancestry. Information about best levels of breed
      composition would be useful for future breeding ctivities, aiming at
      trypanotolerant animals with higher productive capacity. 

PMID- 25964797
TI  - Editorial: "Ion channels and mental illness: exploring etiology and
      pathophysiology in major psychiatric disorders".

PMID- 25964799
TI  - Who qualifies to be a bioinformatician?

PMID- 25964800
TI  - A novel population balance model for the dilute acid hydrolysis of hemicellulose.
AB  - BACKGROUND: Acid hydrolysis is a popular pretreatment for removing hemicellulose
      from lignocelluloses in order to produce a digestible substrate for enzymatic
      saccharification. In this work, a novel model for the dilute acid hydrolysis of
      hemicellulose within sugarcane bagasse is presented and calibrated against
      experimental oligomer profiles. The efficacy of mathematical models as hydrolysis
      yield predictors and as vehicles for investigating the mechanisms of acid
      hydrolysis is also examined. RESULTS: Experimental xylose, oligomer (degree of
      polymerisation 2 to 6) and furfural yield profiles were obtained for bagasse
      under dilute acid hydrolysis conditions at temperatures ranging from 110 degrees
      C to 170 degrees C. Population balance kinetics, diffusion and porosity evolution
      were incorporated into a mathematical model of the acid hydrolysis of sugarcane
      bagasse. This model was able to produce a good fit to experimental xylose yield
      data with only three unknown kinetic parameters k a ,k b and k d . However,
      fitting this same model to an expanded data set of oligomeric and furfural yield
      profiles did not successfully reproduce the experimental results. It was found
      that a "hard-to-hydrolyse" parameter, alpha, was required in the model to ensure
      reproducibility of the experimental oligomer profiles at 110 degrees C, 125
      degrees C and 140 degrees C. The parameters obtained through the fitting
      exercises at lower temperatures were able to be used to predict the oligomer
      profiles at 155 degrees C and 170 degrees C with promising results. CONCLUSIONS:
      The interpretation of kinetic parameters obtained by fitting a model to only a
      single set of data may be ambiguous. Although these parameters may correctly
      reproduce the data, they may not be indicative of the actual rate parameters,
      unless some care has been taken to ensure that the model describes the true
      mechanisms of acid hydrolysis. It is possible to challenge the robustness of the
      model by expanding the experimental data set and hence limiting the parameter
      space for the fitting parameters. The novel combination of "hard-to-hydrolyse"
      and population balance dynamics in the model presented here appears to stand up
      to such rigorous fitting constraints.

PMID- 25964801
TI  - Rational design of polymer-based absorbents: application to the fermentation
      inhibitor furfural.
AB  - BACKGROUND: Reducing the amount of water-soluble fermentation inhibitors like
      furfural is critical for downstream bio-processing steps to biofuels. A
      theoretical approach for tailoring absorption polymers to reduce these
      pretreatment contaminants would be useful for optimal bioprocess design. RESULTS:
      Experiments were performed to measure aqueous furfural partitioning into polymer
      resins of 5 bisphenol A diglycidyl ether (epoxy) and polydimethylsiloxane (PDMS).
      Experimentally measured partitioning of furfural between water and PDMS, the more
      hydrophobic polymer, showed poor performance, with the logarithm of PDMS-to-water
      partition coefficient falling between -0.62 and -0.24 (95% confidence). In
      contrast, the fast setting epoxy was found to effectively partition furfural with
      the logarithm of the epoxy-to-water partition coefficient falling between 0.41
      and 0.81 (95% confidence). Flory-Huggins theory is used to predict the
      partitioning of furfural into diverse polymer absorbents and is useful for
      predicting these results. CONCLUSION: We show that Flory-Huggins theory can be
      adapted to guide the selection of polymer adsorbents for the separation of low
      molecular weight organic species from aqueous solutions. This work lays the
      groundwork for the general design of polymers for the separation of a wide range
      of inhibitory compounds in biomass pretreatment streams.

PMID- 25964798
TI  - Genomic imprinting effects on complex traits in domesticated animal species.
AB  - Monoallelically expressed genes that exert their phenotypic effect in a parent-of
      origin specific manner are considered to be subject to genomic imprinting, the
      most well understood form of epigenetic regulation of gene expression in mammals.
      The observed differences in allele specific gene expression for imprinted genes
      are not attributable to differences in DNA sequence information, but to specific
      chemical modifications of DNA and chromatin proteins. Since the discovery of
      genomic imprinting some three decades ago, over 100 imprinted mammalian genes
      have been identified and considerable advances have been made in uncovering the
      molecular mechanisms regulating imprinted gene expression. While most genomic
      imprinting studies have focused on mouse models and human biomedical disorders,
      recent work has highlighted the contributions of imprinted genes to complex trait
      variation in domestic livestock species. Consequently, greater understanding of
      genomic imprinting and its effect on agriculturally important traits is predicted
      to have major implications for the future of animal breeding and husbandry. In
      this review, we discuss genomic imprinting in mammals with particular emphasis on
      domestic livestock species and consider how this information can be used in
      animal breeding research and genetic improvement programs. 

PMID- 25964802
TI  - Modern insulins, old paradigms and pragmatism: choosing wisely when deciding how
      to treat type 1 diabetes.
AB  - There is a clinical imperative to improve metabolic control in the treatment of
      patients with type 1 diabetes, but in doing so, hypoglycemia should be avoided at
      all costs. Insulin analogues and the assumption they would better mimic the
      pharmacokinetic profile of endogenous insulin secretion emerged as a magic bullet
      in the treatment of patients with type 1 diabetes. However, although insulin
      analogues have pharmaceutical properties, such as pharmacodynamic stability,
      reproducibility of action, and a more physiological timing of action, which could
      possibly facilitate insulin use, the results obtained in clinical practice have
      not been as good as expected. Like all clinical decisions, the decision regarding
      which insulin would be better for the patient should be, if possible, evidence
      based. Here, we briefly discuss evidence for the use of insulin analogues and the
      different views with respect to the available evidence that lead to different
      interpretations and decisions regarding the use of this new technology. 

PMID- 25964804
TI  - Validity of the established method of quantifying home advantage in soccer.

PMID- 25964803
TI  - The significance of ductoscopy of mammary ducts in the diagnostics of breast
      neoplasms.
AB  - INTRODUCTION: Ductoscopy is a low invasive method enabling the diagnostics of
      intraductal proliferative lesions in breasts. Fiberoptic ductoscopy (FDS) is
      important in the diagnosis of patients with pathological nipple discharge. There
      are attempts to apply FDS in patients with breast cancer without the presence of
      nipple discharge. AIM: To assess fiberoptic ductoscopy in the diagnostics of
      breast neoplasms. MATERIAL AND METHODS: The material was composed of a group of
      164 patients treated for intraductal proliferative lesions in breasts. In the
      analyzed group of patients, FDS was conducted in 128 patients with pathological
      nipple discharge and 36 patients with the presence of breast cancer. The analyzed
      period was divided into three sub-periods. Sensitivity, specificity, positive
      predictive value (PPV) and negative predictive value (NPV) of FDS examination
      verified by post-operative histopathological examination were analyzed. The
      safety of the method was also assessed, taking into consideration the
      complications. RESULTS: An increasing number of successful ductoscopies together
      with the number of performed FDS examinations was noted. There were statistically
      significant differences in the percentage of successful cannulations in relation
      to the number of performed FDS examinations in the three subsequent stages of the
      project (p = 0.011). The duration of FDS examination in the third period was
      reduced in comparison with the first and second period (p < 0.001). Sensitivity
      of fiberoptic ductoscopy is 68.1%, specificity 77.3% and PPV 90.4%, but NPV is
      44.1%. CONCLUSIONS: The introduction of fiberoptic ductoscopy in our clinic has
      contributed to the widening of the diagnostic possibilities of small intraductal
      lesions of the mammary gland.

PMID- 25964805
TI  - Do ergogenic AIDS alter lower extremity joint alignment during a functional
      movement lunge prior to and following an exercise bout?
AB  - Ergogenic aids have been used to alter joint kinematics in an attempt to minimise
      injury risk, yet the effectiveness of these aids may be compromised following a
      bout of exercise. This preliminary study aimed to measure the effect of
      compression garments and Kinesio Tape(r) on lower extremity joint alignment prior
      to and following an exercise bout. Eight male athletes (age = 24.1 +/- 3.0 years,
      body height = 177.4 +/- 5.2 cm, body mass = 72.3 +/- 7.2 kg) volunteered to
      participant in this study. Joint kinematics were recorded whilst all participants
      performed three rotational lunges, in three conditions (control, compression
      garment, Kinesio Tape(r)), prior to and following a 10 minute exercise bout.
      Frontal plane kinematics (lateral pelvic tilt, knee valgus, ankle
      inversion/eversion) were used to assess ergogenic aid effectiveness during the
      lunge. Participants exhibited no significant differences in joint kinematics
      between ergogenic aid conditions prior to the exercise bout. Following exercise
      the only significant difference occurred within the Kinesio Tape(r) condition
      where maximum knee valgus angle significantly increased from 6.5 degrees  prior
      to exercise, to 7.7 degrees  following the exercise bout. The results of this
      study suggest joint kinematics are not affected by the ergogenic aids in this
      study prior to an exercise bout. However, there is evidence to suggest that the
      application of Kinesio Tape(r) may allow an increase in knee valgus angle
      following a bout of exercise, yet, compression garments are effective at
      maintaining joint alignment following a bout of exercise. 

PMID- 25964806
TI  - Reproducibility and validity of the myotest for measuring step frequency and
      ground contact time in recreational runners.
AB  - The purpose of this study was to assess the reproducibility (test-retest
      reliability and agreement) and concurrent validity of the Myotest for measuring
      step frequency (SF) and ground contact time (GCT) in recreational runners. Based
      on a within-subjects design (test and retest), SF and GCT of 14 participants (11
      males, 3 females) were measured at three different running speeds with the
      Myotest during two test sessions. SF and GCT were also assessed with a foot
      mounted accelerometer (Gold Standard, previously validated by comparing to force
      plate data) during the first test session. Levels of test-retest reliability and
      concurrent validity were expressed with intraclass correlation coefficients
      (ICC), agreement with standard errors of measurement (SEM). For SF, test-retest
      reliability (ICC's > 0.75) and agreement of the Myotest were considered as good
      at all running speeds. For GCT, test-retest reliability was found to be moderate
      at a running speed of 14 km/h and poor at speeds of 10 and 12 km/h (ICC < 0.50).
      Agreement of the Myotest for GCT at all three running speeds was considered not
      acceptable given the SEM's calculated. Concurrent validity of the Myotest with
      the foot-mounted accelerometer (Gold Standard) at all three running speeds was
      found to be good for SF (ICC's > 0.75) and moderate for GCT (0.50 < ICC's <
      0.75). The conclusion of our study is that estimates obtained with the Myotest
      are reproducible and valid for SF but not for GCT. 

PMID- 25964807
TI  - Six weeks of core stability training improves landing kinetics among female
      capoeira athletes: a pilot study.
AB  - Core stability training (CST) has increased in popularity among athletes and the
      general fitness population despite limited evidence CST programmes alone lead to
      improved athletic performance. In female athletes, neuromuscular training
      combining balance training and trunk and hip/pelvis dominant CST is suggested to
      reduce injury risk, and specifically peak vertical ground reaction forces (vGRF)
      in a drop jump landing task. However, the isolated effect of trunk dominant core
      stability training on vGRF during landing in female athletes had not been
      evaluated. Therefore, the objective of this study was to evaluate landing
      kinetics during a drop jump test following a CST intervention in female capoeira
      athletes. After giving their informed written consent, sixteen female capoeira
      athletes (mean +/- SD age, stature, and body mass of 27.3 +/- 3.7 years, 165.0 +/
      4.0 cm, and 59.7 +/- 6.3 kg, respectively) volunteered to participate in the
      training program which consisted of static and dynamic CST sessions, three times
      per week for six weeks. The repeated measures T-test revealed participants
      significantly reduced relative vGRF from pre- to post-intervention for the first
      (3.40 +/- 0.78 vs. 2.85 +/- 0.52 N.NBW-1, respectively [p<0.05, effect size =
      0.60]), and second landing phase (5.09 +/- 1.17 vs. 3.02 +/- 0.41 N.NBW-1,
      respectively [p<0.001, effect size = 0.87]). The average loading rate was reduced
      from pre- to post-intervention during the second landing phase (30.96 +/- 18.84
      vs. 12.06 +/- 9.83 N.NBW.s-1, respectively [p<0.01, effect size = 0.68]). The
      peak loading rate was reduced from pre- to post-intervention during the first
      (220.26 +/- 111.51 vs. 120.27 +/- 64.57 N.NBW.s-1 respectively [p<0.01, effect
      size = 0.64]), and second (99.52 +/- 54.98 vs. 44.71 +/- 30.34 N.NBW.s-1
      respectively [p<0.01, effect size = 0.70]) landing phase. Body weight, average
      loading rate during the first landing phase, and jump height were not
      significantly different between week 0 and week 6 (p=0.528, p=0.261, and p=0.877,
      respectively). This study provides evidence that trunk dominant core stability
      training improves landing kinetics without improving jump height, and may reduce
      lower extremity injury risk in female athletes. 

PMID- 25964808
TI  - The effects of bag style on muscle activity of the trapezius, erector spinae and
      latissimus dorsi during walking in female university students.
AB  - Back pain is common in adolescents which has been associated with carrying a bag.
      However, there is little research examining the effects of bag style in female
      adolescents. The aim of the study was to investigate the effects of different bag
      conditions on muscle activity of the trapezius, erector spinae and latissimus
      dorsi muscles in female university students during walking. Twelve female
      university students walked on a treadmill for 5 minutes at 1.1 m/s during five
      conditions; control, 1 strapped rucksack, 2 strapped rucksack, ipsilateral
      shoulder strap and contralateral shoulder strap, each containing 10% bodyweight.
      Electromyography for the trapezius, erector spinae and latissimus dorsi was
      recorded for the last 30 s of each condition. Two-way ANOVA and paired t-tests
      were used to identify differences between right and left muscles and between bag
      conditions. Results showed that muscle activity of the left trapezius was
      significantly higher than the right trapezius during the 1 strap rucksack
      condition. For the left trapezius, the 2 strapped rucksack and the control
      condition had significantly lower muscle activity compared to the 1 strapped
      rucksack and the ipsilateral shoulder strap. For the left erector spinae muscle,
      there was significantly greater muscle activity when wearing the contralateral
      shoulder strap compared to the control. For the right erector spinae,
      significantly lower muscle activity was observed when wearing the 2 strapped
      rucksack compared to the ipsilateral shoulder strap and contralateral shoulder
      strap. There were no significant differences in muscle activity of the latissimus
      dorsi muscles between any of the bag conditions. These findings suggest that a
      two strapped rucksack should be used when carrying loads to reduce spinal muscle
      activity which may, in turn, reduce reports of back pain in female adolescents. 

PMID- 25964809
TI  - Influence of passive stiffness of hamstrings on postural stability.
AB  - The aim of the study was to explore whether passive stiffness of the hamstrings
      influences the strategy of maintaining postural stability. A sample of 50
      subjects was selected; the final analyses were based on data of 41 individuals
      (33 men, 8 women) aged 21 to 29 (mean = 23.3, SD = 1.1) years. A quasi-
      experimental ex post facto design with repeated measures was used. Categories of
      independent variables were obtained directly prior to the measurement of the
      dependent variables. In stage one of the study, passive knee extension was
      measured in the supine position to assess hamstring stiffness. In stage two, the
      magnitude of postural sway in antero-posterior direction was measured, while
      varying the body position on a stabilometric platform, both with and without
      visual control. The margin of safety was used as a measure of postural control.
      The magnitude of the margin of safety increased significantly between the open
      eye and closed-eye trials. However, although we registered a visible tendency for
      a larger increase of the margin of safety associated with lower levels of passive
      hamstrings stiffness, no significant differences were found. Therefore, this
      study demonstrated that hamstring stiffness did not influence the strategy used
      to maintain postural stability. 

PMID- 25964810
TI  - Lower extremity strength and the range of motion in relation to squat depth.
AB  - The purpose of this study was to determine which variables of the range of motion
      (ROM) and strength of the hip, and ankle are associated with squat depth. In
      total, 101 healthy subjects (64 males, 37 females) participated in the study.
      Outcome measures consisted of the ROM of hip flexion, hip internal rotation,
      external rotation, ankle dorsiflexion with an extended and flexed knee joint, and
      strength of the hip flexor and ankle dorsiflexor. Squat depth was measured using
      SIMI motion analysis software. Pearson correlation was used to determine the
      relationship between variables and squat depth. Multiple stepwise regression
      analysis was performed to determine variables associated with squat depth. The
      multiple regression model indicated that ankle dorsiflexion with a flexed knee
      and the hip flexion ROM were significantly associated with squat depth in male
      subjects (R(2) = 0.435) and ankle dorsiflexion with an extended knee and
      dorsiflexor strength were significantly associated with squat depth in female
      subjects (R(2) = 0.324). Thus, exercises to increase the ROM of the ankle
      dorsiflexion, hip flexion, and dorsiflexor strength can be recommended to improve
      squat performance. Future studies should assess an increased ROM of the ankle
      dorsiflexion, hip flexion, or dorsiflexor strength effect on deep squat
      performance. 

PMID- 25964811
TI  - The relationships between the center of mass position and the trunk, hip, and
      knee kinematics in the sagittal plane: a pilot study on field-based video
      analysis for female soccer players.
AB  - Athletes with non-contact anterior cruciate ligament tears have common features
      in the sagittal plane; namely, the body's center of mass (COM) is located
      posterior to the base of support, the trunk and knee joints are extended, and the
      hip angle is flexed. However, the relationships among these variables have not
      been assessed in field-based movements. This study sought to determine
      relationships between distances from the COM to the base of support and the
      trunk, hip, and knee positions in women while playing soccer. Sixty events (29
      single-leg landing and 31 single-leg stopping events) were analyzed using two
      dimensional video analysis. The relationships among the measurement variables
      were determined using the Pearson's product-moment correlation coefficient, and
      stepwise multiple linear regression models were used to explore the relationships
      between the COM position and the kinematic variables. The distance from the COM
      to the base of support displayed a moderate negative relationship with the trunk
      angle (r = -0.623, p < .0001, r(2) = 0.388) and a strong positive relationship
      with the limb angle (r = 0.869, p < .0001, r(2) = 0.755). The limb, knee, and
      trunk angles were selected in the best regression model (adjusted r(2) = 0.953, p
      < .0001, f(2) = 20.277). These findings suggest that an increased trunk angle and
      a decreased limb angle at initial contact are associated with a safer COM
      position. Neuromuscular training may be useful for controlling the trunk and
      lower limb positions during dynamic activities. 

PMID- 25964812
TI  - Mechanical, hormonal and psychological effects of a non-failure short-term
      strength training program in young tennis players.
AB  - This study examined the effects of a 6-week non-failure strength training program
      in youth tennis players. Twenty tennis players (age: 15.0 +/- 1 years, body
      height: 170.9 +/- 5.1 cm, body mass: 63.3 +/- 9.1 kg) were divided into
      experimental and control groups. Pre and post-tests included half squats, bench
      press, squat jumps, countermovement-jumps and side-ball throws. Salivary cortisol
      samples were collected, and the Profile of Mood States questionnaire was used
      weekly during an anatomical adaptation period, a main training period and after a
      tapering week. The results showed that, after the main training period, the
      experimental group significantly improved (p<0.05) in mean and peak power output
      and in the total number of repetitions during the half-squat endurance test; mean
      force, power and velocity in the half-squat power output test; Profile of Mood
      States (in total mood disturbance between the last week of the mean training
      period and the tapering week); and in squat-jump and countermovement-jump height.
      Moreover, significant differences were found between the groups at the post-tests
      in the total number of repetitions, mean and peak power during the half-squat
      endurance test, mean velocity in the half-squat power output test, salivary
      cortisol concentration (baselines, first and third week of the mean training
      period) and in the Profile of Mood States (in fatigue subscale: first and third
      week of the mean training period). In conclusion, a non-failure strength training
      protocol improved lower-limb performance levels and produced a moderate
      psychophysiological impact in youth elite tennis players, suggesting that it is a
      suitable program to improve strength. Such training protocols do not increase the
      total training load of tennis players and may be recommended to improve strength.

PMID- 25964813
TI  - Damage to Liver and Skeletal Muscles in Marathon Runners During a 100 km Run With
      Regard to Age and Running Speed.
AB  - The purpose of this study was to determine: (1) whether damage to liver and
      skeletal muscles occurs during a 100 km run; (2) whether the metabolic response
      to extreme exertion is related to the age or running speed of the participant;
      (3) whether it is possible to determine the optimal running speed and distance
      for long-distance runners' health by examining biochemical parameters in venous
      blood. Fourteen experienced male amateur ultra-marathon runners, divided into two
      age groups, took part in a 100 km run. Blood samples for liver and skeletal
      muscle damage indexes were collected from the ulnar vein just before the run,
      after 25, 50, 75 and 100 km, and 24 hours after termination of the run. A
      considerable increase in alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST) was observed with the distance covered (p < 0.05), which
      continued during recovery. An increase in the mean values of lactate
      dehydrogenase (LDH), creatine kinase (CK) and C-reactive protein (CRP) (p < 0.05)
      was observed with each sequential course. The biggest differences between the age
      groups were found for the activity of liver enzymes and LDH after completing 75
      km as well as after 24 hours of recovery. It can be concluded that the response
      to extreme exertion deteriorates with age in terms of the active movement
      apparatus. 

PMID- 25964814
TI  - The Variants Within the COL5A1 Gene are Associated with Reduced Risk of Anterior
      Cruciate Ligament Injury in Skiers.
AB  - The purpose of this study was to examine the association of the BstUI RFLP C/T
      (rs 12722) and DpnII RFLP C/T (rs 13946) COL5A1 polymorphisms, individually and
      as haplotypes, with anterior cruciate ligament ruptures in recreational skiers.
      Subjects were 138 male recreational skiers with surgically diagnosed primary
      anterior cruciate ligament ruptures. The control group consisted of 183
      apparently healthy male recreational skiers, who were without any self-reported
      history of ligament or tendon injury. DNA was extracted from buccal cells donated
      by the subjects and genotyping was carried out using real-time PCR. The genotype
      distributions for both polymorphisms met Hardy-Weinberg expectations in both
      groups. There were no significant differences in genotype distribution of allele
      frequencies of COL5A1 BstUI RFLP C/T and COL5A1 DpnII RFLP C/T polymorphisms
      between the ACL rupture and control groups. The T-T (BstUI RFLP T, DpnII RFLP T)
      haplotype was the most common (55.6%). The haplotype T-C was not present in any
      of the subjects. There was an underrepresentation tendency of the C-T haplotype
      in the study group compared to controls under recessive mode of inheritance.
      Higher frequency of the COL5A1 BstUI RFLP C/T and COL5A1DpnII RFLP C/T
      polymorphisms haplotype is associated with reduced risk of anterior cruciate
      ligament injury in a group of apparently healthy male recreational skiers. 

PMID- 25964815
TI  - Effect of nordic walking and water aerobics training on body composition and the
      blood flow in lower extremities in elderly women.
AB  - Nordic walking and water aerobics are very popular forms of physical activity in
      the elderly population. The aim of the study was to evaluate the influence of
      regular health training on the venous blood flow in lower extremities and body
      composition in women over 50 years old. Twenty-four women of mean age 57.9 (+/-
      3.43) years, randomly divided into three groups (Nordic walking, water aerobics,
      and non-training), participated in the study. The training lasted 8 weeks, with
      one-hour sessions twice a week. Dietary habits were not changed. Before and after
      training vein refilling time and the function of the venous pump of the lower
      extremities were measured by photoplethysmography. Body composition was
      determined by bioelectrical impedance. Eight weeks of Nordic walking training
      improved the venous blood flow in lower extremities and normalized body
      composition in the direction of reducing chronic venous disorder risk factors.
      The average values of the refilling time variable (p = 0.04, p = 0.02,
      respectively) decreased in both the right and the left leg. After training a
      statistically significant increase in the venous pump function index was found
      only in the right leg (p = 0.04). A significant increase in fat-free mass, body
      cell mass and total body water was observed (p = 0.01), whereas body mass, the
      body mass index, and body fat decreased (p < 0.03). With regard to water aerobic
      training, no similar changes in the functions of the venous system or body
      composition were observed. 

PMID- 25964816
TI  - Using network metrics in soccer: a macro-analysis.
AB  - The aim of this study was to propose a set of network methods to measure the
      specific properties of a team. These metrics were organised at macro-analysis
      levels. The interactions between teammates were collected and then processed
      following the analysis levels herein announced. Overall, 577 offensive plays were
      analysed from five matches. The network density showed an ambiguous relationship
      among the team, mainly during the 2nd half. The mean values of density for all
      matches were 0.48 in the 1st half, 0.32 in the 2nd half and 0.34 for the whole
      match. The heterogeneity coefficient for the overall matches rounded to 0.47 and
      it was also observed that this increased in all matches in the 2nd half. The
      centralisation values showed that there was no 'star topology'. The results
      suggest that each node (i.e., each player) had nearly the same connectivity,
      mainly in the 1st half. Nevertheless, the values increased in the 2nd half,
      showing a decreasing participation of all players at the same level. Briefly,
      these metrics showed that it is possible to identify how players connect with
      each other and the kind and strength of the connections between them. In summary,
      it may be concluded that network metrics can be a powerful tool to help coaches
      understand team's specific properties and support decision-making to improve the
      sports training process based on match analysis. 

PMID- 25964817
TI  - Selected determinants of acceleration in the 100m sprint.
AB  - The goal of this study was to examine the relationship between kinematics, motor
      abilities, anthropometric characteristics, and the initial (10 m) and secondary
      (30 m) acceleration phases of the 100 m sprint among athletes of different
      sprinting performances. Eleven competitive male sprinters (10.96 s +/- 0.36 for
      100 with 10.50 s fastest time) and 11 active students (12.20 s +/- 0.39 for 100 m
      with 11.80 s fastest time) volunteered to participate in this study. Sprinting
      performance (10 m, 30 m, and 100 m from the block start), strength (back squat,
      back extension), and jumping ability (standing long jump, standing five-jumps,
      and standing ten-jumps) were tested. An independent t-test for establishing
      differences between two groups of athletes was used. The Spearman ranking
      correlation coefficient was computed to verify the association between variables.
      Additionally, the Ward method of hierarchical cluster analysis was applied. The
      recorded times of the 10 and 30 m indicated that the strongest correlations were
      found between a 1-repetition maximum back squat, a standing long jump, standing
      five jumps, standing ten jumps (r = 0.66, r = 0.72, r = 0.66, and r = 0.72), and
      speed in the 10 m sprint in competitive athletes. A strong correlation was also
      found between a 1-repetition maximum back squat and a standing long jump,
      standing five jumps, and standing ten jumps (r = 0.88, r = 0.87 and r = 0.85),
      but again only for sprinters. The most important factor for differences in
      maximum speed development during both the initial and secondary acceleration
      phase among the two sub-groups was the stride frequency (p<0.01). 

PMID- 25964818
TI  - Strength, Endurance, Throwing Velocity and in-Water Jump Performance of Elite
      German Water Polo Players.
AB  - The purpose of this study was threefold: 1) to assess the eggbeater kick and
      throwing performance using a number of water polo specific tests, 2) to explore
      the relation between the eggbeater kick and throwing performance, and 3) to
      investigate the relation between the eggbeater kick in the water and strength
      tests performed in a controlled laboratory setting in elite water polo players.
      Fifteen male water polo players of the German National Team completed dynamic and
      isometric strength tests for muscle groups (adductor, abductor, abdominal,
      pectoralis) frequently used during water polo. After these laboratory strength
      tests, six water polo specific in-water tests were conducted. The eggbeater kick
      assessed leg endurance and agility, maximal throwing velocity and jump height. A
      400 m test and a sprint test examined aerobic and anaerobic performance. The
      strongest correlation was found between jump height and arm length (p < 0.001, r
      = 0.89). The laboratory diagnostics of important muscles showed positive
      correlations with the results of the in-water tests (p < 0.05, r = 0.52-0.70).
      Muscular strength of the adductor, abdominal and pectoralis muscles was
      positively related to in-water endurance agility as assessed by the eggbeater
      kick (p < 0.05; r = 0.53-0.66). Findings from the current study emphasize the
      need to assess indices of water polo performance both in and out of the water as
      well as the relation among these parameters to best assess the complex profile of
      water polo players. 

PMID- 25964819
TI  - The Gluteus Medius Vs. Thigh Muscles Strength Ratio and Their Relation to
      Electromyography Amplitude During a Farmer's Walk Exercise.
AB  - The strength ratio between hamstrings and quadriceps (H/Q) is associated with
      knee injuries as well as hip abductor muscle (HAB) weakness. Sixteen resistance
      trained men (age, 32.5 +/- 4.2 years) performed 5 s maximal isometric
      contractions at 75 degrees  of knee flexion/extension and 15 degrees  of hip
      abduction on a dynamometer. After this isometric test they performed a Farmer's
      walk exercise to find out if the muscle strength ratio predicted the
      electromyography amplitude expressed as a percentage of maximum voluntary
      isometric contraction (%MVIC). The carried load represented a moderate intensity
      of 75% of the exercise six repetitions maximum (6RM). Electromyography data from
      the vastus medialis (VM), vastus lateralis (VL), biceps femoris (BF) and gluteus
      medius (Gmed) on each leg were collected during the procedure. The groups
      selected were participants with H/Q >= 0.5, HQ < 0.5, HAB/H >= 1, HAB/H < 1,
      HAB/Q >= 0.5 and HAB/Q < 0.5. One way ANOVA showed that Gmed activity was
      significantly greater in the group with HAB/H < 1 (42 +/- 14 %MVIC) as compared
      to HAB/H >= 1 (26 +/- 10 %MVIC) and HAB/Q < 0.5 (47 +/- 19 %MVIC) compared to
      HAB/Q >= 0.5 (26 +/- 12 %MVIC). The individuals with HAB/H < 1 were found to have
      greater activation of their Gmed during the Farmer's walk exercise. Individuals
      with HAB/Q < 0.5 had greater activation of the Gmed. Gmed strength ratios predict
      the muscle involvement when a moderate amount of the external load is used. The
      Farmer's walk is recommended as an exercise which can strengthen the gluteus
      medius, especially for individuals with a HAB/H ratio < 1 and HAB/Q < 0.5. 

PMID- 25964820
TI  - Muscle torque and its relation to technique, tactics, sports level and age group
      in judo contestants.
AB  - The aim of this study was to perform a comparative analysis of maximal muscle
      torques at individual stages of development of athletes and to determine the
      relationship between muscle torques, fighting methods and the level of sports
      performance. The activity of 25 judo contestants during judo combats and the
      effectiveness of actions were evaluated. Maximum muscle torques in
      flexors/extensors of the body trunk, shoulder, elbow, hip and knee joints were
      measured. The level of significance was set at p<=0.05; for multiple comparisons
      the Mann-Whitney U test, p<=0.016, was used. Intergroup differences in relative
      torques in five muscle groups studied (elbow extensors, shoulder flexors, knee
      flexors, knee extensors, hip flexors) were not significant. In cadets, relative
      maximum muscle torques in hip extensors correlated with the activity index
      (Spearman's r=0.756). In juniors, maximum relative torques in elbow flexors and
      knee flexors correlated with the activity index (r=0.73 and r=0.76,
      respectively). The effectiveness of actions correlated with relative maximum
      torque in elbow extensors (r=0.67). In seniors, the relative maximum muscle
      torque in shoulder flexors correlated with the activity index during the second
      part of the combat (r=0.821). 

PMID- 25964821
TI  - Acute effects of different stretching techniques on the number of repetitions in
      a single lower body resistance training session.
AB  - This study aimed to investigate the acute effects of passive static and ballistic
      stretching on maximal repetition performance during a resistance training session
      (RTS). Nine male subjects underwent three experimental conditions: ballistic
      stretching (BS); passive static stretching (PSS); and a specific warm-up (SW).
      The RTS was composed of three sets of 12RM for the following exercises: leg press
      45 (LP), leg extension (LE), leg curl (LC), and plantar flexors (PF). Performance
      of six sessions was assessed 48 hours apart. The first visit consisted of a
      familiarization session including stretching methods and exercises used in the
      RTS. On the second and third visit, a strength test and retest were performed.
      During the fourth to the sixth visit, the volunteers randomly performed the
      following protocols: BS+RTS; PSS+RTS; or SW+RTS. For the sum of the RM number of
      each three-set exercise, significant differences were found between PSS vs. SW
      for the LP (p = 0.001); LE (p = 0.005); MF (p = 0.001); and PF (p = 0.038). For
      the comparison between the methods of stretching PSS vs. BS, significant
      differences were found only for the FP (p = 0.019). When analyzing the method of
      stretching BS vs. SW, significant differences were found for the LP (p = 0.014)
      and MF (p = 0.002). For the total sum of the RM number of three sets of the four
      exercises that composed the RTS, significant differences were observed (p < 0.05)
      in the following comparisons: PPS vs. SW (p = 0.001), PPS vs. BS (p = 0.008), and
      BS vs. SW (p = 0.002). Accordingly, the methods of passive static and ballistic
      stretching should not be recommended before a RTS. 

PMID- 25964822
TI  - Relationships between the yo-yo intermittent recovery test and anaerobic
      performance tests in adolescent handball players.
AB  - The aim of the present study was to investigate relationships between a
      performance index derived from the Yo-Yo Intermittent Recovery Test level 1 (Yo
      Yo IR1) and other measures of physical performance and skill in handball players.
      The other measures considered included peak muscular power of the lower limbs
      (Wpeak), jumping ability (squat and counter-movement jumps (SJ, CMJ), a handball
      skill test and the average sprinting velocities over the first step (VS) and the
      first 5 m (V5m). Test scores for 25 male national-level adolescent players (age:
      17.2 +/- 0.7 years) averaged 4.83 +/- 0.34 m.s(-1) (maximal velocity reached at
      the Yo-Yo IR1); 917 +/- 105 Watt, 12.7 +/- 3 W.kg(-1) (Wpeak); 3.41 +/- 0.5 m.s(
      1) and 6.03 +/- 0.6 m.s(-1) (sprint velocities for Vs and V5m respectively) and
      10.3 +/- 1 s (handball skill test). Yo-Yo IR1 test scores showed statistically
      significant correlations with all of the variables examined: Wpeak (W and W.kg(
      1)) r = 0.80 and 0.65, respectively, p<=0.001); sprinting velocities (r = 0.73
      and 0.71 for VS and V5m respectively; p<=0.001); jumping performance (SJ: r =
      0.60, p<=0.001; CMJ: r= 0.66, p<=0.001) and the handball skill test (r = 0.71;
      p<=0.001). We concluded that the Yo-Yo test score showed a sufficient correlation
      with other potential means of assessing handball players, and that intra
      individual changes of Yo-Yo IR1 score could provide a useful composite index of
      the response to training or rehabilitation, although correlations lack sufficient
      precision to help in players' selection. 

PMID- 25964823
TI  - Body composition of elite female players in five different sports games.
AB  - The goal of this study was to identify and compare body composition (BC)
      variables in elite female athletes (age +/- years): volleyball (27.4 +/- 4.1),
      softball (23.6 +/- 4.9), basketball (25.9 +/- 4.2), soccer (23.2 +/- 4.2) and
      handball (24.0 +/- 3.5) players. Fat-free mass (FFM), fat mass, percentage of fat
      mass (FMP), body cell mass (BCM), extracellular mass (ECM), their ratio, the
      percentage of BCM in FFM, the phase angle (alpha), and total body water, with a
      distinction between extracellular (ECW) and intracellular water, were measured
      using bioimpedance analysis. MANOVA showed significant differences in BC
      variables for athletes in different sports (F60.256 = 2.93, p < 0.01, eta2 =
      0.407). The results did not indicate any significant differences in FMP or alpha
      among the tested groups (p > 0.05). Significant changes in other BC variables
      were found in analyses when sport was used as an independent variable. Soccer
      players exhibited the most distinct BC, differing from players of other sports in
      8 out of 10 variables. In contrast, the athletes with the most similar BC were
      volleyball and basketball players, who did not differ in any of the compared
      variables. Discriminant analysis revealed two significant functions (p < 0.01).
      The first discriminant function primarily represented differences based on the
      FFM proportion (volleyball, basketball vs. softball, soccer). The second
      discriminant function represented differences based on the ECW proportion
      (softball vs. soccer). Although all of the members of the studied groups competed
      at elite professional levels, significant differences in the selected BC
      variables were found. The results of the present study may serve as normative
      values for comparison or target values for training purposes. 

PMID- 25964824
TI  - Detection of the Lactate Threshold in Runners: What is the Ideal Speed to Start
      an Incremental Test?
AB  - Incremental tests on a treadmill are used to evaluate endurance athletes;
      however, no criterion exists to determine the intensity at which to start the
      test, potentially causing the loss of the first lactate threshold. This study
      aimed to determine the ideal speed for runners to start incremental treadmill
      tests. The study consisted of 94 runners who self-reported the average speed from
      their last competitive race (10-42.195 km) and performed an incremental test on a
      treadmill. The speeds used during the first three test stages were normalised in
      percentages of average competition speed and blood lactate concentration was
      analysed at the end of each stage. The relationship between speed in each stage
      and blood lactate concentration was analysed. In the first stage, at an intensity
      corresponding to 70% of the reported average race speed, only one volunteer had
      blood lactate concentration equal to 2 mmol.L(-1), and in the third stage (90% of
      the average race speed) the majority of the volunteers had blood lactate
      concentration >=2 mmol.L(-1). Our results demonstrated that 70% of the average
      speed from the subject's last competitive race - from 10 to 42.195 km - was the
      best option for obtaining blood lactate concentration <2 mmol.L(-1) in the first
      stage, however, 80% of the average speed in marathons may be a possibility.
      Evaluators can use 70% of the average speed in competitive races as a strategy to
      ensure that the aerobic threshold intensity is not achieved during the first
      stage of incremental treadmill tests. 

PMID- 25964825
TI  - Association between sports participation and sedentary behavior during school
      recess among brazilian adolescents.
AB  - The aim of this study was to examine the association between sports participation
      and sedentary behavior during school recess among Brazilian adolescents. This
      study included 2,243 adolescents aged 13-18 years (16.2 +/- 1.1), 62.2% females
      and 37.8% males, enrolled in public high schools in Aracaju, Northeastern Brazil.
      Sedentary behavior during school recess and sport participation was self
      reported. Several factors were examined, including sex, age, skin color,
      socioeconomic status, maternal education and physical activity level. Sixty
      percent of adolescents had sedentary behavior during school recess and 57.7% of
      adolescents reported that they did not participate in any team sport.
      Additionally, adolescents who did not practice any team sport were 40% more
      likely (OR: 1.4, 95% CI: 1.1, 1.8) to be sedentary during school recess compared
      to those who participated in two or more team sports. It is recommended that
      schools encourage students to engage in sports activities and promote more
      physical activity during school recess to reduce the sedentary behavior and
      increase physical activity levels in youth. 

PMID- 25964826
TI  - Outcomes of the Rope Skipping 'STAR' Programme for Schoolchildren.
AB  - Physical activity in children and adolescents is on a decline trend. To this end,
      we conducted a matched-pair randomized controlled trial to examine the effects of
      a 4-week STAR (School-based; Train-the-trainer; Accessibility of resources;
      Recreational) skipping programme. 1,386 schoolchildren from 20 primary and
      secondary schools were recruited. Schools were randomized into the experimental
      or wait-list control group. Participants self-reported their health-related
      quality of life using the KIDSCREEN-27. Accelerometers were used to measure the
      time a subgroup of participants (n = 480) spent in moderate-to-vigorous physical
      activity during school hours on five consecutive days. Measures were taken at pre
      and post-test. At post-test, students in the experimental group, compared to
      those in the control group, engaged in less moderate-to-vigorous physical
      activity during school hours. Health-related quality of life from two groups of
      students was similar, but the experimental group reported higher levels of
      autonomy and parent relationships. Results suggested that although the
      intervention did not increase students' physical activity levels, it slightly
      improved their health-related quality of life. Future studies should explore
      personal factors that might mediate the effect of the intervention. 

PMID- 25964827
TI  - Intrinsic and extrinsic motivation among adolescent ten-pin bowlers in kuala
      lumpur, malaysia.
AB  - Motivation has long been associated with sports engagement. However, to date no
      research has been performed to understand the domain of motivation among ten-pin
      bowlers. The purpose of this study was to investigate different types of
      motivation (i.e., intrinsic vs. extrinsic) based on self-determination theory
      from the perspective of gender and the bowler type (competitive vs. casual). A
      total of 240 bowlers (104 male, 136 female; 152 competitive, 88 casual) with a
      mean age of 16.61 +/- 0.78 years were recruited in Kuala Lumpur. The Sport
      Motivation Scale, a 28-item self-report questionnaire measuring seven subscales
      (i.e., intrinsic motivation to know, intrinsic motivation to accomplish,
      intrinsic motivation to experience stimulation, extrinsic motivation to identify
      regulation, extrinsic motivation for introjection regulation, extrinsic
      motivation to external regulation, and amotivation) was administered. Results
      showed significant differences (t=10.43, df=239, p=0.01) between total scores of
      intrinsic and extrinsic motivation among ten-pin bowlers. There were significant
      gender differences with respect to intrinsic motivation to know, intrinsic
      motivation to accomplish, intrinsic motivation to experience stimulation, and
      extrinsic motivation to identify regulation. However, no significant bowler type
      differences were found for either the intrinsic (t=-1.15, df=238, p=0.25) or
      extrinsic (t=-0.51, df=238, p=0.61) motivation dimensions. In conclusion, our
      study demonstrated substantial intrinsic motivation for gender effects, but no
      bowler type effects among adolescent ten-pin bowlers. 

PMID- 25964828
TI  - Global initiative of the special olympics movement for people with intellectual
      disabilities.
AB  - The mission of the Special Olympics is to provide year-round sports training and
      competition in a variety (33) of Olympic-type sports for children and adults with
      intellectual disabilities, giving them continuing opportunities to develop
      physical fitness, demonstrate courage, experience joy, and participate in sharing
      of gifts and friendship with their families, other athletes, and their
      communities. The Special Olympics movement often goes beyond the sports
      competition formula. During the last few years, the movement has developed many
      new global initiatives, which expand its former sports activities. They include:
      Coaching excellence and the coaching modelPartnerships with international
      (regional) sports federationsSports Resources Teams (SRT)Extended quota for high
      level athletesAthletes Leadership Program (ALPS)Young Athletes ProgramYouth
      volunteer initiativesUnified Sports ProgramMotor Activity Training ProgramHealthy
      Athletes Program These initiatives fulfill and expand the existing program, which
      was launched in 1968 and is the largest sports organization for people with
      disabilities worldwide, with very important new social, marketing, and
      developmental aspects of life, going far beyond activities met in other sports
      organizations. 

PMID- 25964829
TI  - Toward a customized program to promote physical activity by analyzing exercise
      types in adolescent, adult, and elderly koreans.
AB  - The purpose of this study was to examine the relationship between the perceived
      physical health status of Korean adolescents, adults, and elderly adults and
      their frequency, intensity, time, and duration of exercise. In 2012, 1,144
      adolescents (under 18 years old), 6,474 adults (19-64 years old), and 1,382
      elderly adults (over 65 years old) participated in the Korean Survey on Citizens'
      Sports Participation Project (N = 9,000). The association between self-reported
      health status and exercise was assessed using multivariate logistic regression
      analyses, controlling for sex and age. The study found that the health status of
      adolescents showed little or no association with the frequency, intensity, time,
      or duration of exercise. However, the health status of adults and elderly Koreans
      was associated with the frequency, intensity, time, and duration of exercise. The
      physical condition and health status of adolescents was better than that of
      adults and the elderly, many of whom had declining health. Our findings show the
      need for exercise-promotion programs customized for particular age groups. The
      limitations and strengths of the study are discussed, as well as the implications
      for future research and managerial applications for promoting exercise in each
      age group. 

PMID- 25964830
TI  - Is response-guided therapy being applied in the clinical setting? The hepatitis C
      example.
AB  - BACKGROUND: Response-guided therapy (RGT) is a treatment model that bases
      adjustments to therapeutic regimens on individualized patient physiologic
      response. This approach is applied to patients with chronic hepatitis C virus
      (HCV) infection who are treated with a triple therapy regimen of boceprevir or
      telaprevir in combination with pegylated interferon and ribavirin. As RGT expands
      in other pharmacologic regimens, including the treatment of breast cancer and
      acute myeloid leukemia, a measurement of how this approach is applied in clinical
      practice is important to determine whether the benefits of RGT are being
      optimized. OBJECTIVE: To measure adherence to the RGT guidelines and to the
      treatment futility rules based on the drug labeling information for boceprevir
      and for telaprevir in the treatment of patients with chronic HCV infection.
      METHODS: A retrospective observational cohort study was conducted using the large
      Humana research database, which includes pharmacy, medical, and laboratory
      claims, as well as enrollment data for more than 1.5 million fully insured
      commercial members, 1.9 million Medicare Advantage members, and 2.4 million
      Medicare Part D members from all 50 states. The study population included
      patients aged >=18 years to <90 years who were fully insured with commercial or
      Medicare Advantage coverage. A pharmacy claim for boceprevir or telaprevir was
      used to identify patients receiving triple therapy for HCV infection. Medical,
      pharmacy, and laboratory claims were reviewed from the date of the first
      boceprevir or telaprevir pharmacy claim between May 2011 and February 2012
      through a 32-week follow-up period, during which patients were required to have
      continuous health plan enrollment eligibility. This time period allowed for the
      occurrences of required HCV RNA laboratory monitoring and the assessment of
      treatment patterns. The use of RGT for boceprevir and telaprevir includes the
      monitoring of HCV RNA levels at routine intervals to determine how to proceed
      with therapy. Adherence to HCV RNA monitoring was measured as the proportion of
      eligible patients who had an HCV RNA assay at each of the recommended time
      intervals. According to futility rules, patients with greater-than-expected HCV
      RNA levels are deemed to be nonresponders and should discontinue therapy.
      Adherence to futility rules was measured as the proportion of patients who
      stopped therapy among all patients who had an HCV RNA result, which indicated
      treatment futility at each monitoring interval. RESULTS: A total of 326 patients
      (65 in the boceprevir group; 261 in the telaprevir group) were eligible for the
      HCV RNA monitoring analysis, and 134 patients (20 receiving boceprevir and 114
      receiving telaprevir) were eligible for the futility rules analysis. There were
      1203 HCV RNA assays during the follow-up period. The percentage of patients who
      were adherent to HCV RNA monitoring during the entire treatment period was 29.2%
      in the boceprevir group and 32.2% in the telaprevir group. In both treatment
      groups, adherence to HCV RNA monitoring was highest at the first recommended time
      interval, followed by a downward trend in the second and third time intervals.
      Approximately 15% of 134 eligible patients met the futility rules for stopping
      therapy based on HCV RNA assay results, and 55% of those patients stopped the
      therapy in accordance with the treatment futility rules. CONCLUSION: The
      implementation of RGT was suboptimal in this population of patients with chronic
      HCV infection; adherence to HCV RNA monitoring guidelines was less than 33%, and
      adherence to treatment futility rules was less than 50%. Managed care pharmacists
      should identify strategies to increase the adoption of RGT, which may, in turn,
      improve patient care and reduce unnecessary expenditures.

PMID- 25964831
TI  - Diagnosis and treatment of patients with thyroid cancer.
AB  - BACKGROUND: Thyroid cancer is the most common malignancy of the endocrine system,
      representing 3.8% of all new cancer cases in the United States and is the ninth
      most common cancer overall. The American Cancer Society estimates that 62,450
      people in the United States will be diagnosed with thyroid cancer in 2015, and
      1950 deaths will result from the disease. OBJECTIVE: To review the current
      approach to the diagnosis and treatment of patients with thyroid cancer.
      DISCUSSION: Over the past 3 decades, there has been a dramatic increase in the
      number of people diagnosed with thyroid cancer, which may be attributable to the
      wide use of imaging studies, including ultrasounds, computed tomography, magnetic
      resonance imaging, and positron emission tomography scans that incidentally
      detect thyroid nodules. Thyroid cancer is divided into several main types, with
      papillary thyroid cancer being the most common. The treatment options for
      patients with thyroid cancer include the surgical removal of the entire thyroid
      gland (total thyroidectomy), radioactive iodine therapy, and molecular-targeted
      therapies with tyrosine kinase inhibitors. This article summarizes the diagnosis
      and treatment of thyroid cancer, with recommendations from the American Thyroid
      Association regarding thyroid nodules and differentiated thyroid cancer. Recently
      approved drugs and treatment trends are also explored. CONCLUSION: The prognosis
      and treatment of thyroid cancer depend on the tumor type and its stage at the
      time of diagnosis. Many thyroid cancers remain stable, microscopic, and indolent.
      The increasing treatment options for patients with thyroid cancer, including
      therapies that were recently approved by the US Food and Drug Administration,
      have kept the mortality rate from this malignancy low, despite the increase in
      its incidence. Early diagnosis and appropriate treatment can improve prognosis
      and reduce mortality.

PMID- 25964832
TI  - New horizons in geriatric urology.

PMID- 25964833
TI  - Current role of multiparametric magnetic resonance imaging in the management of
      prostate cancer.
AB  - The purpose of this review was to evaluate the current role of multiparametric
      magnetic resonance imaging (mp-MRI) in the management of prostate cancer (PC).
      The diagnosis of PC remains controversial owing to overdetection of indolent
      disease, which leads to overtreatment and subsequent patient harm. mp-MRI has the
      potential to equilibrate the imbalance between detection and treatment. The
      limitation of the data for analysis with this new technology is problematic,
      however. This issue has been compounded by a paradigm shift in clinical practice
      aimed at utilizing this modality, which has been rolled out in an ad hoc fashion
      often with commercial motivation. Despite a growing body of literature, pertinent
      clinical questions remain. For example, can mp-MRI be calibrated to reliably
      detect biologically significant disease? As with any new technology, objective
      evaluation of the clinical applications of mp-MRI is essential. The focus of this
      review was on the evaluation of mp-MRI of the prostate with respect to clinical
      utility. 

PMID- 25964834
TI  - Infection after transrectal ultrasound-guided prostate biopsy.
AB  - Infectious complications after transrectal ultrasound-guided prostate biopsy
      (TRUS-Bx) appear to be increasing, which reflects the high prevalence of
      antibiotic-resistant strains of Enterobacteriaceae. Identifying patients at high
      risk for antibiotic resistance with history taking is an important initial step.
      Targeted prophylaxis with a prebiopsy rectal swab culture or augmented antibiotic
      prophylaxis can be considered for patients at high risk of antibiotic resistance.
      If infectious complications are suspected, the presence of urosepsis should be
      evaluated and adequate antibiotic treatment should be started immediately. 

PMID- 25964835
TI  - Natural 10-year history of simple renal cysts.
AB  - PURPOSE: To carry out long-term follow-up of patients diagnosed with asymptomatic
      simple renal cysts (SRCs). MATERIALS AND METHODS: One hundred fifty-eight adult
      patients in whom SRCs were incidentally diagnosed by abdominal ultrasonography or
      abdominopelvic computed tomography between August 1994 and June 2004 were
      followed up for over 10 years. The retrospective analysis investigated sequential
      changes in the size, shape, and Bosniak classification of the renal cyst and
      analyzed risk factors for increased size and growth rate of the cysts. RESULTS:
      The median follow-up period was 13.9 years (range, 10.0-19.8 years). Median
      patient age was 54.1 years (range, 22-86 years). Mean maximal cyst size was 33 mm
      (range, 2-90 mm). Among all patients, 120 (76%) showed a mean increase in maximum
      renal cyst diameter of 1.4 mm (6.4%) per year. Age at initial diagnosis was a
      risk factor for increased renal cyst maximum diameter. The probability of an
      increase in maximum diameter of an SRC was 7.1 times greater in patients aged 50
      years or older at diagnosis than in those aged less than 50 years. However, among
      patients with an increased maximum diameter, the mean growth rate was lower in
      patients aged >=50 years than in those aged <50 years. CONCLUSIONS: About three
      quarters of adult patients with accidentally diagnosed SRCs presented with an
      increased maximum diameter. The only risk factor for an increase in maximum
      diameter was age. In patients with an increase in the maximum diameter, the
      growth rate of the maximum diameter was 6.4% per year during 10 years and
      decreased with age.

PMID- 25964836
TI  - Does skip metastasis or other lymph node parameters have additional effects on
      survival of patients undergoing radical cystectomy for bladder cancer?
AB  - PURPOSE: To investigate the effects of lymph node metastasis, skip metastasis,
      and other factors related to lymph node status on survival in patients who
      underwent radical cystectomy (RC) and extended lymph node dissection (eLND).
      MATERIALS AND METHODS: RC and eLND were performed in 85 patients with a diagnosis
      of bladder cancer. Disease-free survival (DFS) and overall survival (OS) were
      determined by using a Cox proportional hazards model that included the number of
      excised lymph nodes, the presence of pathological lymph node metastasis, the
      anatomical level of positive nodes, the number of positive lymph nodes, lymph
      node density, and the presence of skip metastasis. RESULTS: The mean number of
      lymph nodes removed per patient was 29.4+/-9.3. Lymph node positivity was
      detected in 85 patients (34.1%). The mean follow-up duration was 44.9+/-27.4
      months (2-93 months). Five-year estimated OS and DFS for the 85 patients were
      62.6% and 57%, respectively. Three of 29 lymph node-positive patients (10.3%) had
      skip metastasis. Only lymph node positivity had a significant effect on 5-year OS
      and DFS (p<0.001). No difference in OS and DFS was found between the three
      patients with skip metastasis and other lymph node-positive patients. Other
      factors related to lymph node status had no significant effect on 5-year OS and
      DFS. CONCLUSIONS: No factors related to lymph node status predict DFS and OS,
      except for lymph node positivity. OS and DFS were comparable between patients
      with skip metastasis and other lymph node-positive patients.

PMID- 25964837
TI  - One day surgery in the treatment of benign prostatic enlargement with thulium
      laser: A single institution experience.
AB  - PURPOSE: Various articles have previously addressed the introduction of new
      surgical laser therapies for an enlarged prostate gland causing obstructive
      symptoms. The objective of this study was to report the feasibility of performing
      the thulium laser vapo-enucleation of the prostate (ThuVEP) procedure for benign
      prostatic obstruction in a 1-day surgery. MATERIALS AND METHODS: From September
      2011 to September 2013, we conducted a prospective study on patients who
      underwent ThuVEP in a 1-day surgery. The primary outcomes measured
      perioperatively included operative time, resected tissue weight, hemoglobin
      decrease, transfusion rate, postoperative irrigation and catheterization time,
      and postoperative hospital stay. Also, the preoperative and postoperative
      International Prostate Symptom Score (IPSS) and results of uroflowmetry performed
      on the 7th and 30th postoperative days were recorded. All perioperative and
      postoperative complications were monitored. RESULTS: A total of 53 patients
      underwent the surgical treatment in a 1-day surgery. Seven patients continued
      antiaggregant therapy with aspirin. Mean preoperative prostatic adenoma volume
      was 56.6 mL. Mean operative time was 71 minutes. The average catheter time was
      14.8 hours. The peak urinary flow rate on day 7 improved from 9.3 to 17.42 mL/s
      (p<0.001) and the IPSS improved from 18 to 10.2 (p<0.01). Patients were routinely
      discharged on the day of catheter removal. No complications were recorded.
      CONCLUSIONS: ThuVEP can be safely conducted as a 1-day surgical procedure. This
      strategy results in cost savings. ThuVEP shows good standardized outcomes with
      respect to improvement in flow parameters and length of bladder catheterization.

PMID- 25964838
TI  - Is intravesical stent position a predictor of associated morbidity?
AB  - PURPOSE: Temporary drainage of the upper urinary tract by use of internal
      ureteral stents is a common procedure that is often associated with a variety of
      symptoms. The role of intravesical stent position in associated morbidity is
      controversial. MATERIALS AND METHODS: The German version of the ureteral stent
      symptom questionnaire (USSQ) was completed by 73 patients with an indwelling
      ureteral stent the day before stent removal. Intravesical stent position was
      classified into 3 categories by x-ray before stent removal. The influence of
      intravesical stent position on USSQ score was analyzed, including subscores and
      single items. RESULTS: Intravesical stent position showed no significant
      influence on associated morbidity. The median USSQ total score in all patients
      was 77.5 (range, 30-147). Patients with ipsilateral stents (69.0; range, 30-122)
      tended to have lower total scores than did those with tangential (86.5; range, 30
      122) or contralateral (77.0; range, 31-147) stents, but the differences were not
      statistically significant (p=0.35). The USSQ subscores for urinary symptoms
      (p=0.80), body pain (p=0.80), general health (p=0.16), work performance (p=0.07),
      additional problems (p=0.81), and all of the USSQ single items of interest in the
      context of stent length also did not differ significantly between the three
      groups. CONCLUSIONS: Intravesical stent position did not significantly influence
      associated morbidity in our study. An appropriate stent length should be chosen
      to avoid dislocation. However, complex calculations of optimum stent length, time
      consuming manipulations, and costly stock holding of various stent sizes to
      obtain the perfect stent position do not seem worthwhile.

PMID- 25964839
TI  - The effect of renal cortical thickness on the treatment outcomes of kidney stones
      treated with shockwave lithotripsy.
AB  - PURPOSE: Because the shock wave passes through various body tissues before
      reaching the stone, stone composition may affect the treatment efficacy of shock
      wave lithotripsy (SWL). We investigated the effect of various tissue components
      along the shock wave path on the success of SWL. MATERIALS AND METHODS: From
      October 2008 to August 2010, a total of 206 patients with kidney stones sized 5
      to 20 mm were prospectively recruited for a study of the factors that affect the
      outcome of treatment with a Sonolith Vision lithotripter. Successful SWL was
      defined as either stone-free status or residual fragments <4 mm at 12 weeks.
      Logistic regression analysis was performed to assess the factors that predicted
      treatment outcomes. Potential predictors included the patient's age, shock wave
      delivery rate, stone volume (SV), mean stone density (MSD), skin-to-stone
      distance (SSD), and the mean thickness of the three main components along the
      shock wave path: renal cortical thickness (KT), muscle thickness (MT), and soft
      tissue thickness (ST). RESULTS: The mean age of the patients was 53.8 years
      (range, 25-82 years). The overall treatment success rate after one session of SWL
      was 43.2%. The mean KT, MT, and ST were 26.9, 16.6, and 40.8 mm, respectively.
      The logistic regression results showed that a slower shock wave delivery rate,
      smaller SV, a lower MSD, and a thicker KT were found to be significant predictors
      for successful SWL. SSD, MT, and ST were not predictors of successful treatment.
      CONCLUSIONS: Among the main tissue components along the shock wave path, a
      thicker KT was a favorable factor for successful SWL after adjustment for SV,
      MSD, and the shock wave delivery rate.

PMID- 25964840
TI  - Body mass index, waist-to-hip ratio, and metabolic syndrome as predictors of
      middle-aged men's health.
AB  - PURPOSE: There is no reported evidence for an anthropometric index that might
      link obesity to men's sexual health. We evaluated the ability of an
      anthropometric index and the symptom scores of five widely used questionnaires to
      detect men's health problems. We determined the predictive abilities of two
      obesity indexes and other clinical parameters for screening for lower urinary
      tract symptoms and sexual dysfunction in middle-aged men. MATERIALS AND METHODS:
      A total of 1,910 middle-aged men were included in the study. Participants
      underwent a detailed clinical evaluation that included recording the symptom
      scores of five widely used questionnaires. The participants' body mass index and
      waist-to-hip ratio were determined. Serum prostate-specific antigen, urinalysis,
      testosterone, estimated glomerular filtration rate, evaluation of metabolic
      syndrome, and transrectal ultrasonography were assessed. RESULTS: By use of
      logistic regression analysis, age and total prostate volume were independent
      predictors of lower urinary tract symptoms. Metabolic syndrome was the only
      significant negative predictive factor for chronic prostatitis symptoms. Age and
      metabolic syndrome were independent predictive factors for erectile dysfunction.
      Waist-to-hip ratio had a statistically significant value for predicting erectile
      dysfunction. CONCLUSIONS: Our data showed that total prostate volume is a
      significant predictor of lower urinary tract symptoms, and central obesity has
      predictive ability for erectile dysfunction. Metabolic syndrome was the only
      significant negative predictive factor for chronic prostatitis-like symptoms. The
      management of correctable factors such as waist-to-hip ratio and metabolic
      syndrome may be considered preventive modalities against the development of men's
      health problems.

PMID- 25964841
TI  - Effect of aging on urodynamic parameters in women with stress urinary
      incontinence.
AB  - PURPOSE: Stress urinary incontinence (SUI) is one of the most common lower
      urinary tract symptoms in women. We analyzed age-associated changes in urodynamic
      parameters in women with SUI. MATERIALS AND METHODS: We analyzed the urodynamic
      study (UDS) results of patients with urodynamically proven SUI between March 2008
      and July 2014. In uroflowmetry, maximal flow rate (Qmax), time to Qmax, voided
      volume, and postvoid residual urine volume (PVR) and filling cystometry data
      including first, strong desire to void and Valsalva leak point pressure (VLPP)
      were measured. Also, Qmax and detrusor pressure at Qmax (Pdet@Qmax) of voiding
      cystometry data were analyzed. RESULTS: The subjects included 776 patients. Among
      the patients, 151 were withdrawn because of incomplete UDS data or because they
      met the exclusion criteria. A total of 625 patients enrolled in our study. The
      mean age of the population was 57.3 years. The mean Qmax, voided volume, voiding
      time, and PVR were 26.2 mL/s, 292.1 mL, 25.7 s, and 31.7 mL, respectively. Qmax
      (p=0.001) in uroflowmetry, PVR (p=0.042), first desire to void (p=0.042),
      Pdet@Qmax (p=0.016), and the bladder contractility index (p=0.046) were
      significantly different between the age groups. Qmax and Pdet@Qmax were decreased
      and PVR was increased significantly with age after 60 years. CONCLUSIONS: Older
      women with SUI also have worsened voiding function with age as the results of
      urodynamic parameters. Specifically, detrusor contractility decreased with age
      after 60 years.

PMID- 25964843
TI  - Knotted stents: Case report and outcome analysis.
AB  - A knotted ureteral stent is an extremely rare condition, with fewer than 20 cases
      reported in the literature; however, it is difficult to treat. We report a case
      in which a folded Terumo guidewire was successfully used to remove a knotted
      stent percutaneously without anesthesia. We also review the current literature on
      predisposing factors and management strategies for knotted ureteral stents. 

PMID- 25964842
TI  - Is a secondary procedure necessary in every case of failed endoscopic treatment
      for vesicoureteral reflux?
AB  - PURPOSE: Endoscopic treatment (ET) has become a widely accepted procedure for
      treating vesicoureteral reflux (VUR). However, patients followed up after ET over
      long periods have reported persistent or recurrent VUR. We evaluated the natural
      course of failed ET in patients who required further treatments to help
      physicians in making decisions on the treatment of VUR. MATERIALS AND METHODS: We
      retrospectively reviewed the medical records of patients who were diagnosed with
      VUR and underwent ET from January 2006 to December 2009. A total of 165 patients
      with 260 ureters underwent ET. We compared the parameters of the patients
      according to ET success or failure and evaluated the natural course of the
      patients after ET failure. RESULTS: Mean VUR grade and positive photon defect
      were higher in the failed ET group than in the successful ET group. Six months
      after the operation, persistent or recurrent VUR was observed in 76 ureters
      (29.2%), and by 16.3 months after the operation, VUR resolution was observed in
      18 ureters (23.7%). Twenty-five ureters (32.9%) without complications were
      observed conservatively. Involuntary detrusor contraction was found in 1 of 9
      (11.1%) among the secondary ET success group, whereas in the secondary ET failure
      group, 4 of 6 (66.7%) had accompanying involuntary detrusor contraction.
      CONCLUSIONS: Patients in whom ET fails can be observed for spontaneous resolution
      of VUR unless they have febrile urinary tract infection or decreased renal
      function. Urodynamic study may be helpful in deciding whether a secondary
      procedure after ET failure is necessary.

PMID- 25964844
TI  - Simple Indirect Enzyme-Linked Immunosorbent Assay to Detect Antibodies Against
      Bovine Viral Diarrhea Virus, Based on Prokaryotically Expressed Recombinant MBP
      NS3 Protein.
AB  - BACKGROUND: Bovine viral diarrhea (BVD) is an economically important disease of
      cattle distributed worldwide. Diagnosis of BVD relies on laboratory-based
      detection of its viral causing agent or virus specific antibodies and the most
      common laboratory method for this purpose is Enzyme-Linked Immunosorbent Assay
      (ELISA). OBJECTIVES: The current study was aimed to develop a simple indirect
      ELISA to detect antibodies against Bovine Viral Diarrhea Virus (BVDV) in the sera
      of infected cattle. MATERIALS AND METHODS: A new simple indirect ELISA method was
      developed to detect BVDV infection by prokaryotically (Escherichia coli, BL21
      strain) expressed recombinant whole nonstructural protein 3 (NS3) of BVDV (NADL
      strain). Four hundred bovine serum samples were evaluated by the newly developed
      NS3-ELISA and virus neutralization test (VNT) as the gold standard method to
      diagnose BVD. Among these samples, 289 sera had been previously tested by a
      commercial ELISA kit. RESULTS: Statistical analyses showed a very high
      correlation between the results of the developed NS3-ELISA and VNT (kappa
      coefficient = 0.935, P < 0.001), with the relative sensitivity and specificity of
      94% and 98.8%, respectively. There was also a high correlation between the
      results of NS3-ELISA and the commercial ELISA kit (kappa coefficient = 0.802, P <
      0.001) with the relative sensitivity and specificity of 90.72% and 91.15%,
      respectively. CONCLUSIONS: The newly developed simple indirect ELISA showed high
      sensitivity and specificity with respect to VNT. Developing such a simple,
      sensitive, and specific ELISA which is much less expensive than the available
      commercial ELISA kits can improve the detection of BVDV infections, help to
      eliminate the disease from herds, and decrease economic losses caused by this
      disease.

PMID- 25964846
TI  - Genetic diversity of blastocystis isolated from cattle in khorramabad, iran.
AB  - BACKGROUND: Blastocystis is a zoonotic protozoan parasite living in the digestive
      system of some vertebrates. This parasite has some subtypes, pathogenicity status
      of which has still remained controversial. OBJECTIVES: The aim of this study was
      to determine the subtype of Blastocystis in infected cattle. MATERIALS AND
      METHODS: This descriptive cross-sectional study was performed on 196 isolates
      from cattle stool samples collected from slaughterhouse in Khorramabad city,
      Iran, in 2012. Genomic DNA was extracted and to determine the Blastocystis
      subtype, seven pairs of sequence-tagged sites (STS) primers were used. RESULTS:
      Of 196 specimens, 19 (9.6%) were infected with Blastocystis. Among the 19
      positive samples, the most common subtype was ST5 (47.36 %), followed by ST3
      (10.53%) and ST6 (10.53%). Two (10.53%) samples had mixed infections by ST3 and
      ST5. The four isolates not amplified by any STS primers were probably unknown
      genotypes. CONCLUSIONS: In the present study, the highest prevalence was for ST5,
      which is so important for epidemiology and risk of human infection. The report
      related to ST3 in cattle as a subtype of human showed mutual infection between
      human and cattle. Another important point in this study was the ST6 report.
      Finally, it seems that gathering epidemiological data is needed for a better
      understanding of the potential animal reservoirs for human infection.

PMID- 25964845
TI  - Hepatitis B virus Genotyping Among Patients With Cirrhosis.
AB  - BACKGROUND: Hepatitis B virus (HBV) infection is a worldwide public health
      problem. Nine HBV genotypes (A-I) have been already discovered. HBV genotypes are
      important both in the clinical manifestation of disease and treatment response.
      Moreover, HBV DNA without HBs (Hepatitis B surface)-antigenemia was detected in
      some patients with chronic hepatitis (occult hepatitis). There is little
      information about HBV genotypes and its relation to occult infection despite the
      importance of this infection in Khuzestan Province. OBJECTIVES: This study aimed
      to determine both occult hepatitis B infection and HBV genotypes among cirrhotic
      patients. PATIENTS AND METHODS: Thirty-eight patients with liver cirrhosis,
      including 11 (28.9%) HBsAg-positive patients and 27 (71.1%) patients with
      cryptogenic cirrhosis participated in this study. The mean age of the patients at
      the time of cirrhosis diagnosis was 54.85 years (range 26-75 years). All patients
      were anti-HCV and anti-HIV negative. For all the samples, the serological Enzyme
      Linked Immunosorbent Assay (ELISA) was performed for HBV markers including HBsAg,
      HBcAb, HBeAg, HBeAb tests. The common primer of S region of HBV was used for
      Nested PCR. The PCR products of the positive individuals were sequenced for
      genotyping and subtyping of HBV. RESULTS: Eleven (40.7%) out of 27 HBV
      cryptogenic cirrhosis and all 11 HBsAg-positive patients were positive for HBV
      DNA. The seroprevalences of Hepatitis B virus HBe antigen, anti-HBe and anti-HBc
      antibodies among the cryptogenic cirrhosis patients were 5 (18.5%), 1 (3.7%), and
      5 (20.83), and among HBsAg-positive patients were 6 (54.5%), 5 (45.5%), and 7
      (63.6%), respectively. CONCLUSIONS: In our study, only HBV genotype D was found
      among all the positive HBsAg and occult HBV infection. Moreover, high prevalence
      (40.7%) of occult HBV infection was determined among patients suffered from
      cryptogenic cirrhosis.

PMID- 25964847
TI  - Oropharyngeal Colonization With Neisseria lactamica, Other Nonpathogenic
      Neisseria Species and Moraxella catarrhalis Among Young Healthy Children in
      Ahvaz, Iran.
AB  - BACKGROUND: Neisseria lactamica as one of the main commensal in oropharynx during
      the childhood is related to the induction of a natural immunity against
      meningococcal meningitis. Also Moraxella catarrhalis in oropharynx of children is
      a predisposing factor for otitis media infection. OBJECTIVES: The current study
      aimed to investigate the frequency of the N. lactamica, other nonpathogenic
      Neisseria spp. and M. catarrhalis in the oropharynx of young healthy children in
      Ahvaz, Iran by the two phenotypic tests and Polymerase Chain Reaction (PCR).
      MATERIALS AND METHODS: A total of 192 oropharyngeal swab samples of the young
      healthy children were studied during four months. Swabs were plated onto enriched
      selective media and non-selective media. Gram-negative and oxidase-positive
      diplococci were identified by several conventional biochemical tests. The PCR and
      sequencing were used to confirm the accuracy of laboratory diagnosis to identify
      N. lactamica and M. catarrhalis. RESULTS: Among 192 young healthy children with
      the mean age of 5.93 +/- 2.5903 years, authors identified: N. lactamica (21.9%)
      in the age group of one to nine years; N. mucosa (6.3%); N. sicca (7.8%); N.
      cinerea (1.6%); N. subflava (biovar subflava) (4.2%); N. subflava (biovar
      perflava) (28.1%); N. subflava (biovar flava) (7.3%) and M. catarrhalis (42.7%).
      CONCLUSIONS: The young healthy children screening by colonization of N. lactamica
      and other nonpathogenic Neisseria spp. in oropharynx was the first report in
      Ahvaz, Iran. The study results demonstrated the high frequency of colonization of
      M. catarrhalis in the studied young healthy children other than Neisseria spp.

PMID- 25964848
TI  - Biofilm Formation and beta-Lactamase Production in Burn Isolates of Pseudomonas
      aeruginosa.
AB  - BACKGROUND: Pseudomonas aeruginosa is an important nosocomial pathogen
      characterized by its innate resistance to multiple antimicrobial agents. Plasmid
      mediated drug resistance also occurs by the production of extended-spectrum beta
      lactamases (ESBL), metallo beta-lactamases (MBL), and AmpC beta-lactamases.
      Another important factor for establishment of chronic infections by P. aeruginosa
      is biofilm formation mediated by the psl gene cluster. OBJECTIVES: The aim of
      this study was to evaluate biofilm formation and presence of the pslA gene in
      burn isolates of P. aeruginosa as well as the association of antibiotic
      resistance, MBL, ESBL and AmpC beta-lactamase production with biofilm formation
      among the isolates. MATERIALS AND METHODS: Sixty-two burn isolates of P.
      aeruginosa were obtained from Shahid Motahari Hospital in Tehran from August to
      October 2011. Antibiotic susceptibility was determined by the disc diffusion
      assay. MBL, AmpC and ESBL production were screened using the double disc synergy
      test, AmpC disc test and combined disc diffusion assay, respectively. The
      potential to form biofilm was measured using the microtiter plate assay and pslA
      gene was detected using specific primers and PCR. RESULTS: Biofilm formation was
      observed in 43.5% of the isolates, of which 66.7% produced strong and 33.3%
      formed weak biofilms. All biofilm-positive and 14.2% of biofilm-negative isolates
      harbored the pslA gene. MBL, AmpC and ESBL production were significantly higher
      in the biofilm-positive isolates (70.3%, 62.9% and 33.3%, respectively) compared
      to the biofilm-negative strains (31.4%, 34.2% and 20%, respectively). Overall, 19
      isolates (30.6%) co-produced MBL and AmpC, among which the majority were biofilm
      positive (63.1%). Finally, four isolates (6.4%) had all three enzymes, of which 3
      (75%) produced biofilm. CONCLUSIONS: Biofilm formation (both strong and weak)
      strongly correlated with pslA gene carriage. Biofilm formation also correlated
      with MBL and AmpC beta-lactamase production. More importantly, multiple-beta
      lactamase phenotype was associated with formation of strong biofilms.

PMID- 25964849
TI  - Merkel cell polyomavirus infection in a patient with merkel cell carcinoma: a
      case report.
AB  - INTRODUCTION: Merkel cell carcinoma (MCC) is a rare and highly aggressive
      malignancy of the skin which occurs mainly in old people and is very uncommon in
      young individuals. A new tumor virus belonging to the Polyomaviridae family;
      Merkel Cell Polyomavirus (MCPyV) has recently been identified in more than 80% of
      MCCs. CASE PRESENTATION: We conducted a retrospective review on the archives of
      the Department of Pathology; Imam Khomeini Hospital Cancer Institute affiliated
      to Tehran University of Medical Sciences to confirm the MCC samples and we found
      medical records and samples of a young case with MCC who developed leg skin and
      scalp tumor six and seven years after bone marrow transplantation, respectively.
      We analyzed patient formalin-fixed paraffin-embedded samples for the presence of
      MCPyV DNA using polymerase chain reaction (PCR) method, and the PCR amplicons
      were subjected to DNA sequencing. Merkel Cell Polyomavirus DNA was detected in
      both tumors from patient and sequence analysis of the viral LT3 region showed a
      close homology to strains circulating worldwide. CONCLUSIONS: The findings of
      this study are consistent with the hypothesis that local, systemic, or tumor
      induced immunosuppression may allow the MCPyV to initiate skin aggressive cancer.
      It is necessary to maintain regular check over patients taking immunosuppressive
      medications for MCPyV infection. Since there is not any information about
      detection and molecular biology analysis of MCPyV among Iranian patients with
      MCC, this study provides more information about MCC and MCPyV in Iran.

PMID- 25964850
TI  - Evaluating drug-drug interaction information in NDF-RT and DrugBank.
AB  - BACKGROUND: There is limited consensus among drug information sources on what
      constitutes drug-drug interactions (DDIs). We investigate DDI information in two
      publicly available sources, NDF-RT and DrugBank. METHODS: We acquire drug-drug
      interactions from NDF-RT and DrugBank, and normalize the drugs to RxNorm. We
      compare interactions between NDF-RT and DrugBank and evaluate both sources
      against a reference list of 360 critical interactions. We compare the
      interactions detected with NDF-RT and DrugBank on a large prescription dataset.
      Finally, we contrast NDF-RT and DrugBank against a commercial source. RESULTS:
      DrugBank drug-drug interaction information has limited overlap with NDF-RT (24
      30%). The coverage of the reference set by both sources is about 60%. Applied to
      a prescription dataset of 35.5M pairs of co-prescribed systemic clinical drugs,
      NDF-RT would have identified 808,285 interactions, while DrugBank would have
      identified 1,170,693. Of these, 382,833 are common. The commercial source Multum
      provides a more systematic coverage (91%) of the reference list. CONCLUSIONS:
      This investigation confirms the limited overlap of DDI information between NDF-RT
      and DrugBank. Additional research is required to determine which source is
      better, if any. Usage of any of these sources in clinical decision systems should
      disclose these limitations.

PMID- 25964851
TI  - Age- and sex-specific differences in blood-borne microvesicles from apparently
      healthy humans.
AB  - BACKGROUND: Sex differences in incidence of cardiovascular disease may reflect
      age-associated intravascular cellular activation resulting in shedding of cell
      membrane-derived bioactive microvesicles (MV or microparticles) into the blood.
      Concentrations of cell-specific MV in blood have the potential to be a
      diagnostic/prognostic marker of pathology, but ranges of MV must first be
      established in healthy individuals. This study identified cellular origin of
      blood-borne MV >0.2 MUm in blood of apparently healthy women and men aged from 20
      70 years. METHODS: Venous blood from apparently healthy participants in the Mayo
      Clinic Biobank was collected into tubes containing protease inhibitors as the
      anticoagulant. MV were isolated by standardized differential centrifugation and
      characterized by digital flow cytometer. Each cellular origin of MV was verified
      by two different antibodies with strong correlation between the two distinct
      antibodies (e.g., for platelet-derived MV, r (2) = 0.97). RESULTS: MV derived
      from platelets were the most abundant type of MV in blood from women and men in
      all age groups. Total numbers of phosphatidylserine, P-selectin, and platelet-
      and endothelium-derived MV were significantly (P < 0.05) greater in women than
      men. Numbers of MV from erythrocytes and stem/progenitor cells were significantly
      lower in premenopausal women than age-matched men. Number of tissue factor
      pathway inhibitor positive MV were significantly (P < 0.05) lower whereas
      erythrocyte-derived MV were significantly higher in postmenopausal women compared
      to premenopausal women. In women, there was a positive relationship between age
      and erythrocyte-derived MV (rho = 0.28; P = 0.009), while in men adipocyte
      derived MV increased with age (rho = 0.33; P = 0.01). CONCLUSIONS: This study
      provides ranges for cellular origin of blood-borne MV in age-matched, apparently
      healthy women and men from which to compare diagnostic and prognostic uses of
      blood-borne MV in larger studies and patient population. In addition, sex- and
      age-specific differences in phosphatidylserine, platelet-, endothelium-,
      erythrocyte-, and adipocyte-derived blood-borne MV may contribute to differential
      progression of cardiovascular disease in women compared to men.

PMID- 25964852
TI  - The global activity limitation indicator and self-rated health: two complementary
      predictors of mortality.
AB  - BACKGROUND: The purpose of this study is to compare the ability of the Global
      Activity Limitation Indicator (GALI) and self-rated health (SRH) to predict all
      cause mortality in the general adult population. METHODS: We linked the 2001
      Belgian Health Interview Survey with mortality and migration registers 2001-2010.
      The baseline sample included 8,583 individuals aged 15 years and older. Poisson
      regression models were used to estimate the effect of the GALI and SRH on
      mortality rate during follow-up. We investigated the impact of gender, age,
      education and follow-up period on the association between the GALI/SRH and
      mortality. RESULTS: The GALI and SRH were strong and complementary predictors of
      mortality in the Belgian adult population. Although the two global instruments
      shared some traits, they predicted mortality concurrently, with some indication
      of a somewhat stronger effect for SRH. We found neither significant differences
      between men and women, nor between education groups. The predictive effect of the
      GALI and SRH slightly decreased over time and the predictive effect of SRH
      slightly decreased with age. CONCLUSIONS: Our findings suggest that the GALI and
      SRH are useful and complementary measures for assessing the health and functional
      status of adults in population surveys.

PMID- 25964853
TI  - Reversible methotrexate-associated lymphoma of the liver in rheumatoid arthritis:
      a unique case of primary hepatic lymphoma.
AB  - Primary hepatic lymphoma (PHL) is an extremely rare disease, frequently
      associated with viruses such as hepatitis B virus (HBV), hepatitis C virus (HCV),
      and human immune deficiency virus (HIV). On the other hand, an increased risk of
      lymphoproliferative disorders (LPD) has been demonstrated in patients treated
      with immunosuppressive drugs such as methotrexate (MTX) for rheumatoid arthritis
      (RA). The role of Epstein-Barr virus (EBV) has been discussed in the pathogenesis
      of the immunodeficiency-associated LPDs. We here describe a RA patient, who
      developed PHL during RA treatment. The patient was a 64 year-old Japanese male
      with a 2-year history of RA, who had been treated with MTX at weekly dose of 8-14
      mg for 2 years and infliximab (IFX) for 7 months. He presented with a 2 month
      history of generalized malaise, right hypochondrium pain and fever. Contrast
      enhanced computed tomography (CECT) of the abdomen showed multiple irregular and
      nodular liver masses with a maximum of 13 cm in diameter on the right liver.
      Biopsy specimens demonstrated CD20-positve diffuse large B-cell lymphoma (DLBCL),
      but EBV was not identified by EBV-encoded RNA in situ hybridization. Serology for
      HBV, HCV, human T-cell leukemia virus I (HTLV-I), and HIV was negative. His
      symptoms disappeared following discontinuation of RA treatment including MTX. A
      drastic regression of the tumor masses was further obtained without cytotoxic
      chemotherapy. In addition, although the patient had no past history of liver
      dysfunction before MTX therapy, persistent elevation of liver enzymes has been
      observed during MTX treatment. These findings show a causative role of MTX in the
      development of reversible PHL in the patient. 

PMID- 25964854
TI  - Rapid start-up and improvement of granulation in SBR.
AB  - BACKGROUND: The aim of this study is to accelerate and improve aerobic
      granulation within a Sequencing Batch Reactor (SBR) by cationic polymer addition.
      METHODS: To identify whether the polymer additive is capable of enhancing granule
      formation, two SBRs (R1 and R2, each 0.15 m in diameter and 2 m in height) are
      used by feeding synthetic wastewater. The cationic polymer with concentration of
      30 to 2 ppm is added to R2, while no cationic polymer is added to R1. RESULTS:
      Results show that the cationic polymer addition causes faster granule formation
      and consequently shorter reactor start-up period. The polymer-amended reactor
      contains higher concentration of biomass with better settling ability (23%
      reduction in SVI15) and larger and denser granules (112% increase of granular
      diameter). In addition, the results demonstrate that the cationic polymer improve
      the sludge granulation process by 31% increase in Extracellular Polymer
      Substance(EPS) concentration, 7% increase in Specific Oxygen Uptake Rate(SOUR),
      18% increase in hydrophobicity, and 17% reduction in effluent Mixed Liquor
      Suspended Solid(MLSS) concentration. CONCLUSIONS: Concludingly, it is found that
      using the cationic polymer to an aerobic granular system has the potential to
      enhance the sludge granulation process.

PMID- 25964855
TI  - Efficacy and safety of aluminum chloride in controlling external hemorrhage: an
      animal model study.
AB  - BACKGROUND: Despite all the progress in surgical science, bleeding caused by
      traffic accidents is still one of the challenges surgeons face in saving
      patients' lives. Therefore, introducing an effective method to control external
      bleeding is an important research priority. OBJECTIVES: This study aimed to
      compare the hemostatic effect of aluminum chloride versus simple suturing in
      controlling external bleeding. MATERIALS AND METHODS: This experimental study was
      conducted in Kashan, Iran. In this study, 60 male Wistar rats were randomly
      allocated into six groups. An incision, two centimeters (cm) long and half a cm
      deep, was made on each rat's shaved back skin and the hemostatic time was
      measured once using aluminum chloride with different concentrations (5%, 10%,
      15%, 25%, and 50%) and then using the control method (controlling hemorrhage by
      simple suturing). The skin tissue was assessed for pathological changes. RESULTS:
      The hemostatic time of aluminum chloride 50%, 25%, 15%, 10% and 5% were 8.20 +/-
      0.919, 14.10 +/- 1.37, 21.20 +/- 1.31, 30.80 +/- 1.68 and 42.00 +/- 4.19 seconds,
      respectively. Also, the mean hemostasis time in the control group (suture) was
      84.00 +/- 4.05 seconds. The hemostatic times of different concentrations of
      aluminum chloride were significantly less than that of the control group. There
      was a statistically significant difference between every two hemostatic time. The
      pathologic examination showed the highest frequency of low-grade inflammation
      based on the defined pathological grading. CONCLUSIONS: The aluminum chloride
      method needs less time to control external hemorrhage compared to the control
      method (controlling external hemorrhage by simple suturing). Aluminum chloride is
      an effective agent in controlling external hemorrhage in an animal model.

PMID- 25964856
TI  - Class II-associated invariant chain peptide as predictive immune marker in
      minimal residual disease in acute myeloid leukemia.
AB  - The majority of patients with acute myeloid leukemia (AML) reach complete
      remission after high-dose chemotherapy. Still, half of these patients experience
      a relapse due to presence of minimal residual disease (MRD). Here we discuss the
      poor prognostic role of class II-associated invariant chain peptide (CLIP)
      expression on residual leukemic cells.

PMID- 25964857
TI  - Reversal of natural killer cell exhaustion by TIM-3 blockade.
AB  - Natural killer (NK) cells are innate immune cells that become progressively
      exhausted in advanced stage cancer, crippling their ability to execute antitumor
      functions. We previously characterized the nature of NK cell exhaustion in
      metastatic melanoma patients, reporting a correlation with high expression of TIM
      3. Blockade of this immune checkpoint molecule reversed the exhausted phenotype
      and improved NK cell function.

PMID- 25964858
TI  - Targeting hypoxia at the forefront of anticancer immune responses.
AB  - Hypoxia influences immune checkpoint receptors and their respective ligands. In
      support, we recently demonstrated that hypoxia selectively upregulates programmed
      cell death ligand 1 (PD-L1) on myeloid-derived suppressor cells (MDSCs) via
      hypoxia inducible factor 1 alpha (HIF-1alpha) binding to a hypoxia-response
      element (HRE) in the PD-L1 proximal promoter. Furthermore, blockade of PD-L1
      under hypoxic conditions enhanced MDSC-mediated T-cell activation by attenuating
      MDSC secretion of IL-6 and IL-10.

PMID- 25964859
TI  - Tumor-expressed IL-17D recruits NK cells to reject tumors.
AB  - Antitumor immunity suppresses tumorigenesis, but we do not understand how
      transformed cells initiate those immune responses that are essential for
      effective tumor immunosurveillance. Using the 3-MCA fibrosarcoma model, we
      identified IL-17D as a tumor-expressed cytokine that recruits natural killer
      cells, leading to the polarization of M1 macrophages and tumor rejection.

PMID- 25964860
TI  - Subverting the adaptive immune resistance mechanism to improve clinical responses
      to immune checkpoint blockade therapy.
AB  - The correlation between tumor-infiltrating lymphocyte (TIL)-expression of
      programmed cell death ligand 1 (PD-L1) and clinical responsiveness to the PD-1
      blocking antibody nivolumab implicates adaptive immune evasion mechanisms in
      cancer. We review our findings that tumor cell PD-L1 expression is induced by
      interferon gamma (IFNgamma) producing TILs. We provide a mechanistic rationale
      for combining IFNgamma+ T helper type 1 (Th1)-inducing cancer vaccines with PD-1
      immune checkpoint blockade.

PMID- 25964861
TI  - Atypical chemokine receptor 2: a brake against Kaposi's sarcoma aggressiveness.
AB  - Inflammatory chemokines are instrumental players in cancer-related inflammation
      contributing to numerous steps during tumor progression. In Kaposi's sarcoma, we
      have found that downregulation of the atypical chemokine receptor 2 (ACKR2) by
      the KRAS/BRAF/ERK pathway profoundly affects the tumor microenvironment,
      unleashing accumulation of tumor-associated macrophages that sustains tumor
      growth. This discovery extends our understanding on the role of inflammatory
      chemokines in tumor biology and provides rationale for their therapeutic
      targeting.

PMID- 25964863
TI  - Roadblocks to success for RNA CARs in solid tumors.
AB  - While CAR therapy has begun to demonstrate efficacy, cell-engineering techniques
      that result in permanent genomic modification carry several safety concerns. CAR
      expression driven by RNA creates a platform for delivery of highly-active cell
      therapy while avoiding long-term CAR-driven toxicity. Using models of pediatric
      neuroblastoma, we have found that RNA CAR T cell activity is limited by
      ineffective tumor infiltration.

PMID- 25964862
TI  - Interleukin-6 receptor and its ligand interleukin-6 are opposite markers for
      survival and infiltration with mature myeloid cells in ovarian cancer.
AB  - An increased level of interleukin-6 (IL-6) in epithelial ovarian cancer (EOC) is
      correlated with a worse prognosis. IL-6 stimulates tumor-growth and inflammation.
      We investigated the intricate interaction between the IL-6 signaling pathway and
      tumor-infiltrating myeloid cells (TIMs) to determine their prognostic impact in
      EOC. 160 EOC samples were analyzed for the expression of IL-6, its receptor (IL
      6R) and downstream signaling via pSTAT3 by immunohistochemistry. Triple color
      immunofluorescence confocal microscopy was used to identify myeloid cell
      populations by CD14, CD33, and CD163. The relationship between these markers,
      tumor-infiltrating immune cells, clinical-pathological characteristics and
      survival was investigated. EOC displayed a dense infiltration with myeloid cells,
      in particular of the CD163+ type. The distribution pattern of all myeloid
      subtypes was comparable among the different histological subtypes. Analysis of
      the tumor cells revealed a high expression of IL-6R in 15% and of IL-6 in 23% of
      patients. Interestingly, tumors expressing IL-6 or IL-6R formed two different
      groups. Tumors with a high expression of IL-6R displayed low mature myeloid cell
      infiltration and a longer disease-specific survival (DSS), especially in late
      stage tumors. High expression of IL-6R was an independent prognostic factor for
      survival by multivariate analyses (hazard ratio = 0.474, p = 0.011). In contrast,
      tumors with high epithelial IL-6 expression displayed a dense infiltration of
      mature myeloid cells and were correlated with a shorter DSS. Furthermore, in
      densely CD8+ T-cell infiltrated tumors, the ratio between these lymphoid cells
      and CD163+ myeloid cells was predictive for survival. Thus, IL-6 and IL-6R are
      opposite markers for myeloid cell infiltration and survival.

PMID- 25964864
TI  - Neoadjuvant immunotherapy with chitosan and interleukin-12 to control breast
      cancer metastasis.
AB  - Metastasis accounts for approximately 90% of breast cancer-related deaths.
      Therefore, novel approaches which prevent or control breast cancer metastases are
      of significant clinical interest. Interleukin-12 (IL-12)-based immunotherapies
      have shown promise in controlling metastatic disease, yet modest responses and
      severe toxicities due to systemic administration of IL-12 in early trials have
      hindered clinical application. We hypothesized that localized delivery of IL-12
      co-formulated with chitosan (chitosan/IL-12) could elicit tumor-specific immunity
      and provide systemic protection against metastatic breast cancer while minimizing
      systemic toxicity. Chitosan is a biocompatible polysaccharide derived primarily
      from the exoskeletons of crustaceans. In a clinically relevant resection model,
      mice bearing spontaneously metastatic 4T1 mammary adenocarcinomas received
      intratumoral injections of chitosan/IL-12, or appropriate controls, prior to
      tumor resection. Neoadjuvant chitosan/IL-12 immunotherapy resulted in long-term
      tumor-free survival in 67% of mice compared to only 24% or 0% of mice treated
      with IL-12 alone or chitosan alone, respectively. Antitumor responses following
      chitosan/IL-12 treatment were durable and provided complete protection against
      rechallenge with 4T1, but not RENCA renal adenocarcinoma, cells. Lymphocytes from
      chitosan/IL-12-treated mice demonstrated robust tumor-specific lytic activity and
      interferon-gamma production. Cell-mediated immune memory was confirmed in vivo
      via clinically relevant delayed-type hypersensitivity (DTH) assays. Comprehensive
      hematology and toxicology analyses revealed that chitosan/IL-12 induced
      transient, reversible leukopenia with no changes in critical organ function.
      Results of this study suggest that neoadjuvant chitosan/IL-12 immunotherapy prior
      to breast tumor resection is a promising translatable strategy capable of safely
      inducing to tumor-specific immunity and, in the long term, reducing breast cancer
      mortality due to progressive recurrences.

PMID- 25964867
TI  - Mutant IDH1: An immunotherapeutic target in tumors.
AB  - The discovery of driver mutations in cancers has raised interest in their
      suitability as immunotherapeutic targets. A recent study demonstrates that a
      point mutation in isocitrate dehydrogenase 1 (IDH1R132H), expressed in gliomas
      and other tumors, is presented on human MHC class II and induces a mutation
      specific CD4+ antitumor T cell response in patients and a syngeneic tumor model
      in MHC-humanized mice.

PMID- 25964866
TI  - Quantitative T cell repertoire analysis by deep cDNA sequencing of T cell
      receptor alpha and beta chains using next-generation sequencing (NGS).
AB  - Immune responses play a critical role in various disease conditions including
      cancer and autoimmune diseases. However, to date, there has not been a rapid,
      sensitive, comprehensive, and quantitative analysis method to examine T-cell or B
      cell immune responses. Here, we report a new approach to characterize T cell
      receptor (TCR) repertoire by sequencing millions of cDNA of TCR alpha and beta
      chains in combination with a newly-developed algorithm. Using samples from lung
      cancer patients treated with cancer peptide vaccines as a model, we demonstrate
      that detailed information of the V-(D)-J combination along with complementary
      determining region 3 (CDR3) sequences can be determined. We identified extensive
      abnormal splicing of TCR transcripts in lung cancer samples, indicating the
      dysfunctional splicing machinery in T lymphocytes by prior chemotherapy. In
      addition, we found three potentially novel TCR exons that have not been described
      previously in the reference genome. This newly developed TCR NGS platform can be
      applied to better understand immune responses in many disease areas including
      immune disorders, allergies, and organ transplantations.

PMID- 25964865
TI  - Physical modalities inducing immunogenic tumor cell death for cancer
      immunotherapy.
AB  - The concept of immunogenic cancer cell death (ICD), as originally observed during
      the treatment with several chemotherapeutics or ionizing irradiation, has
      revolutionized the view on the development of new anticancer therapies. ICD is
      defined by endoplasmic reticulum (ER) stress response, reactive oxygen species
      (ROS) generation, emission of danger-associated molecular patterns and induction
      of antitumor immunity. Here we describe known and emerging cancer cell death
      inducing physical modalities, such as ionizing irradiation, ultraviolet C light,
      Photodynamic Therapy (PDT) with Hypericin, high hydrostatic pressure (HHP) and
      hyperthermia (HT), which have been shown to elicit effective antitumor immunity.
      We discuss the evidence of ICD induced by these modalities in cancer patients
      together with their applicability in immunotherapeutic protocols and anticancer
      vaccine development.

PMID- 25964868
TI  - Topical, Aqueous, Clear Cyclosporine Formulation Design for Anterior and
      Posterior Ocular Delivery.
AB  - PURPOSE: The main objective of this study was to optimize cyclosporine (CsA)
      nanomicellar solution and study in vivo ocular CsA tissue distribution with a
      topical drop. METHODS: An optimized blend of hydrogenated castor oil-40 and
      octoxynol-40 was prepared to entrap CsA within nanomicelles. In vivo studies were
      conducted in New Zealand White albino rabbits with topical drop instillation.
      RESULTS: Average size of CsA-loaded nanomicelles was approximately 22.4 nm.
      Ocular tissue CsA quantification with single and multiple dosing revealed that
      CsA levels followed as cornea -> iris-ciliary body -> aqueous humor -> lens.
      Cyclosporine levels were also found to be in the following order: conjunctiva ->
      sclera -> retina/choroid -> vitreous humor. High CsA level was detected in
      retina/choroid (53.7 ng/g tissue). CONCLUSIONS: Ocular tissue CsA distribution
      studies revealed high CsA concentrations in anterior ocular tissues. Moreover, it
      appears that nanomicelles are transported through a conjunctival-scleral pathway
      and deliver CsA to the retina/choroid. Results suggest polymeric blend to be a
      safe carrier for anterior and posterior ocular tissues. TRANSLATIONAL RELEVANCE:
      This study has significant translational relevance, disclosing results that
      suggest that aqueous nanomicellar approach can provide high corneal and
      conjunctival CsA concentrations. Aqueous nanomicelles can deliver high drug
      concentrations not only to anterior but also to back of the eye tissues,
      including retina. This article provides a platform for noninvasive back of the
      eye drug delivery with topical eye drops. Aqueous CsA nanomicelles have no
      perceptible toxicity such as cell membrane damage or cytotoxicity to corneal and
      retinal pigment epithelial cells. Clear aqueous nanomicellar solution can be
      translated to human conditions for keratoconjunctivitis sicca and other anti
      inflammatory conditions.

PMID- 25964869
TI  - TelePain: A Community of Practice for Pain Management.
AB  - INTRODUCTION: Comprehensive pain management services are primarily located in
      urban areas, limiting specialist consultation opportunities for community
      healthcare providers. A community of practice (CoP) for pain management could
      create opportunities for consultation by establishing professional relationships
      between community healthcare providers and pain management specialists. A CoP is
      a group of people with a common concern, set of problems, or a passion for
      something they do. Members of a CoP for pain management increase their knowledge
      of evidence-based pain management strategies in a way that is meaningful and
      relevant. In this article, we provide evidence that TelePain, an
      interdisciplinary, case-based pain management teleconference consultation program
      through the University of Washington, qualifies as a CoP and present preliminary
      evidence of TelePain's effectiveness as a CoP for pain management. METHODS:
      Specific behaviors and conversations gathered through participant observation
      during TelePain sessions were analyzed based on the 14 indicators Wegner
      developed to evaluate the presence of a CoP. To demonstrate preliminary
      effectiveness of TelePain as a CoP for pain management, descriptive statistics
      were used to summarize TelePain evaluation forms. RESULTS: TelePain is an example
      of a successful CoP for pain management as demonstrated by the presence of
      Wegner's 14 indicators. Additionally, evaluation forms showed that TelePain
      enhanced community healthcare providers' knowledge of pain management strategies
      and that continued participation in TelePain lead to community healthcare
      providers' increased confidence in their ability to provide pain management.
      CONCLUSION: TelePain, a CoP for pain management, facilitates multidisciplinary
      collaboration and allows members to develop interdisciplinary care plans for
      complex pain patients through case study discussions. Evidence-based pain
      management strategies gained through CoP membership could be disseminated to
      other healthcare providers in members' clinics, which has the potential of
      improving the care of chronic pain patients.

PMID- 25964870
TI  - Molecular interactions between hepatitis B virus and delta virus.
AB  - As a deficient virus due to the lack of envelope proteins, hepatitis D virus
      (HDV) causes chronic or fulminant "delta hepatitis" only in people with
      simultaneous hepatitis B virus (HBV) infection. HBV encodes three types of
      surface proteins known as small (S), medium (M) and large (L) envelope proteins.
      All three types of HBV surface antigens (HBsAgs) are present on HDV virions. The
      envelopment process of HDV occurs through interactions between the HDV
      ribonucleoprotein (RNP) complex and HBV HBsAgs. While HBsAg is the only protein
      required by HDV, the exact interaction sites between the S protein and pre-mature
      HDV are not well defined yet. In fact, these sites are distributed along the S
      protein with some hot spots for the envelopment process. Moreover, in most
      clinically studied samples, HDV infection is associated with a dramatically
      reduced HBV viral load, temporarily or permanently, while HBsAg resources are
      available for HDV packaging. Thus, beyond interacting with HBV envelope proteins,
      controlling mechanisms exist by which HDV inhibits HBV-DNA replication while
      allowing a selective transcription of HBV proteins. Here we discuss the molecular
      interaction sites between HBsAg and the HDV-RNP complex and address the proposed
      indirect mechanisms, which are employed by HBV and HDV to facilitate or inhibit
      each other's viral replication. Understanding molecular interactions between HBV
      and HDV may help to design novel therapeutic strategies for delta hepatitis. 

PMID- 25964871
TI  - New advances on glial activation in health and disease.
AB  - In addition to being the support cells of the central nervous system (CNS),
      astrocytes are now recognized as active players in the regulation of synaptic
      function, neural repair, and CNS immunity. Astrocytes are among the most
      structurally complex cells in the brain, and activation of these cells has been
      shown in a wide spectrum of CNS injuries and diseases. Over the past decade,
      research has begun to elucidate the role of astrocyte activation and changes in
      astrocyte morphology in the progression of neural pathologies, which has led to
      glial-specific interventions for drug development. Future therapies for CNS
      infection, injury, and neurodegenerative disease are now aimed at targeting
      astrocyte responses to such insults including astrocyte activation, astrogliosis
      and other morphological changes, and innate and adaptive immune responses. 

PMID- 25964874
TI  - Viral hepatitis and human immunodeficiency virus co-infections in Asia.
AB  - Hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency
      virus (HIV) affect many people in Asian countries, although there are geographic
      differences. Both HBV and HIV (HBV/HIV) and HCV/HIV co-infections are highly
      prevalent in Asia. Hetero- and homosexual, injection drug use, and geographic
      area are strong predictors of HBV, HCV, and HIV serostatus. In HBV endemic
      regions, the prevalence and genotype distribution of HBV/HIV co-infection is
      almost comparable with that in the general population. In Japan, where HBV has
      low endemicity, the prevalence of HBV/HIV co-infection is approximately 10-fold
      higher than that in the general population, and HBV Ae is the most common
      subgenotype among HIV infected individuals. Highly active antiretroviral therapy
      (HAART) is an effective treatment for HIV/Acquired Immune Deficiency Syndrome.
      Lamivudine, a component of HAART, is an effective treatment for HBV, HIV, and
      HBV/HIV co-infection; however, cost, emerging drug resistance, antiretroviral
      associated liver toxicity and liver-related morbidity due to HCV progression are
      particular concerns. HCV/HIV co-infection may accelerate the clinical progression
      of both HCV and HIV. The high prevalence of HBV/HIV and HCV/HIV co-infections in
      Asia underscores the need to improve prevention and control measures, as fewer
      evidence-based prevention strategies are available (compared with Western
      countries). In this review, the most recent publications on the prevalence of
      HBV/HIV and HCV/HIV co-infections and related issues, such as therapy and
      problems in Asia, are updated and summarized. 

PMID- 25964872
TI  - Impact of antiretroviral therapy on lipid metabolism of human immunodeficiency
      virus-infected patients: Old and new drugs.
AB  - For human immunodeficiency virus (HIV)-infected patients, the 1990s were marked
      by the introduction of highly active antiretroviral therapy (HAART) representing
      a new perspective of life for these patients. The use of HAART was shown to
      effectively suppress the replication of HIV-1 and dramatically reduce mortality
      and morbidity, which led to a better and longer quality of life for HIV-1
      infected patients. Apart from the substantial benefits that result from the use
      of various HAART regimens, laboratory and clinical experience has shown that
      HAART can induce severe and considerable adverse effects related to metabolic
      complications of lipid metabolism, characterized by signs of lipodystrophy,
      insulin resistance, central adiposity, dyslipidemia, increased risk of
      cardiovascular disease and even an increased risk of atherosclerosis. New drugs
      are being studied, new therapeutic strategies are being implemented, and the use
      of statins, fibrates, and inhibitors of intestinal cholesterol absorption have
      been effective alternatives. Changes in diet and lifestyle have also shown
      satisfactory results. 

PMID- 25964875
TI  - Debunking the myths perpetuating low implementation of isoniazid preventive
      therapy amongst human immunodeficiency virus-infected persons.
AB  - Isoniazid preventive therapy (IPT) is the administration of isoniazid (INH) to
      people with latent tuberculosis (TB) infection (LTBI) to prevent progression to
      active TB disease. Despite being life-saving for human immunodeficiency virus
      (HIV)-infected persons who do not have active TB, IPT is poorly implemented
      globally due to misconceptions shared by healthcare providers and policy makers.
      However, amongst HIV-infected patients especially those living in resource
      limited settings with a high burden of TB, available evidence speaks for IPT:
      Among HIV-infected persons, active TB- the major contraindication to IPT, can be
      excluded with symptom screening; chest X-ray and tuberculin skin testing are
      unreliable and often lead to logistic delays resulting in increased numbers of
      people with LTBI progressing to active TB; the use of IPT has not been found to
      increase the risk of the development of INH mono-resistance; IPT is cost
      effective and cheaper than the cost of treating cases of active TB that would
      develop without IPT; ART and IPT have an additive effect on the prevention of TB,
      and both are safe and beneficial even in children. In order to sustain the
      recorded gains from ART scale-up and to further reduce TB-related morbidity and
      mortality, more efforts are needed to scale-up IPT implementation globally. 

PMID- 25964873
TI  - Therapeutic and prevention strategies against human enterovirus 71 infection.
AB  - Human enterovirus 71 (HEV71) is the cause of hand, foot and mouth disease and
      associated neurological complications in children under five years of age. There
      has been an increase in HEV71 epidemic activity throughout the Asia-Pacific
      region in the past decade, and it is predicted to replace poliovirus as the
      extant neurotropic enterovirus of highest global public health significance. To
      date there is no effective antiviral treatment and no vaccine is available to
      prevent HEV71 infection. The increase in prevalence, virulence and geographic
      spread of HEV71 infection over the past decade provides increasing incentive for
      the development of new therapeutic and prevention strategies against this
      emerging viral infection. The current review focuses on the potential, advantages
      and disadvantages of these strategies. Since the explosion of outbreaks leading
      to large epidemics in China, research in natural therapeutic products has
      identified several groups of compounds with anti-HEV71 activities. Concurrently,
      the search for effective synthetic antivirals has produced promising results.
      Other therapeutic strategies including immunotherapy and the use of
      oligonucleotides have also been explored. A sound prevention strategy is crucial
      in order to control the spread of HEV71. To this end the ultimate goal is the
      rapid development, regulatory approval and widespread implementation of a safe
      and effective vaccine. The various forms of HEV71 vaccine designs are highlighted
      in this review. Given the rapid progress of research in this area, eradication of
      the virus is likely to be achieved. 

PMID- 25964876
TI  - Is transfusion-transmitted dengue fever a potential public health threat?
AB  - Dengue is an arboviruses due to single-stranded enveloped ribonucleic acid
      viruses, named dengue viruses (DENV), that include four serotypes and are mainly
      transmitted via the bite of mosquitoes of the genus Aedes (A. aegypti and A.
      albopictus). The distribution of the disease was historically limited to
      intertropical areas; however, during the last thirty years, the perimeter of the
      disease extended considerably and temperate areas are now at risk of outbreaks.
      The present global burden of dengue is considerable: 2.5 billion people over more
      than 100 countries are concerned; 50 to 100 million infections occur every year,
      with a number of fatal cases of approximately 20000. Although frequently
      asymptomatic or limited to a mild fever, dengue is responsible for severe cases
      mainly consecutive to the occurrence of hemorrhagic complications that can lead
      to shock and death, notably in children from poor-resource settings. The place of
      DENV as a transfusion-transmitted pathogen has been recognized only in 2008. At
      the present time, only five cases of transfusion-transmitted dengue, including
      one case of dengue hemorrhagic fever, have been formerly documented. This review
      provides a general overview of dengue, its viruses and their vectors. It replaces
      the disease in the context of other viral diseases transmitted by arthropods. It
      discusses the threat of dengue on the supply of blood products in endemic and non
      endemic areas. Finally, it describes the specific and non specific measures
      available for improving the security of blood products with regards to this
      emerging risk. Interestingly, in 2009, the American Association of Blood Banks
      placed DENV in the highest category of emerging infectious agents for their
      potential impact on transfusion recipient safety for the next years in North
      America. 

PMID- 25964878
TI  - Early initiation of antiretroviral treatment: Challenges in the Middle East and
      North Africa.
AB  - New World Health Organization guidelines recommend the initiation of
      antiretroviral treatment (ART) for asymptomatic patients with CD4+ T-cell counts
      of <= 500 cells/mm(3). Substantial reduction of human immunodeficiency virus
      (HIV) transmission is addressed as a major public health outcome of this new
      approach. Middle East and North Africa (MENA), known as the area of controversies
      in terms of availability of comprehensive data, has shown concentrated epidemics
      among most of it's at risk population groups. Serious challenges impede the
      applicability of new guidelines in the MENA Region. Insufficient resources
      restrict ART coverage to less than 14%, while only one fourth of the countries
      had reportable data on patients' CD4 counts at the time of diagnosis. Clinical
      guidelines need to be significantly modified to reach practical utility, and
      surveillance systems have not yet been developed in many countries of MENA. Based
      on available evidence in several countries people who inject drugs and men who
      have sex with men are increasingly vulnerable to HIV and viral hepatitis, while
      their sexual partners - either female sex workers or women in monogamous
      relationships with high-risk men - are potential bridging populations that are
      not appropriately addressed by regional programs. Research to monitor the
      response to ART among the mentioned groups are seriously lacking, while drug
      resistant HIV strains and limited information on adherence patterns to treatment
      regimens require urgent recognition by health policymakers. Commitment to defined
      goals in the fight against HIV, development of innovative methods to improve
      registration and reporting systems, monitoring and evaluation of current programs
      followed by cost-effective modifications are proposed as effective steps to be
      acknowledged by National AIDS Programs of the countries of MENA Region. 

PMID- 25964877
TI  - Key role of human leukocyte antigen in modulating human immunodeficiency virus
      progression: An overview of the possible applications.
AB  - Host and viral factors deeply influence the human immunodeficiency virus (HIV)
      disease progression. Among them human leukocyte antigen (HLA) locus plays a key
      role at different levels. In fact, genes of the HLA locus have shown the peculiar
      capability to modulate both innate and adaptive immune responses. In particular,
      HLA class I molecules are recognized by CD8(+) T-cells and natural killers (NK)
      cells towards the interaction with T cell receptor (TCR) and Killer
      Immunoglobulin Receptor (KIR) 3DL1 respectively. Polymorphisms within the
      different HLA alleles generate structural changes in HLA class I peptide-binding
      pockets. Amino acid changes in the peptide-binding pocket lead to the
      presentation of a different set of peptides to T and NK cells. This review
      summarizes the role of HLA in HIV progression toward acquired immunodeficiency
      disease syndrome and its receptors. Recently, many studies have been focused on
      determining the HLA binding-peptides. The novel use of immune-informatics tools,
      from the prediction of the HLA-bound peptides to the modification of the HLA
      receptor complexes, is considered. A better knowledge of HLA peptide presentation
      and recognition are allowing new strategies for immune response manipulation to
      be applied against HIV virus. 

PMID- 25964879
TI  - Cost and safety of assisted reproductive technologies for human immunodeficiency
      virus-1 discordant couples.
AB  - Due to significant advances in the treatment of human immunodeficiency virus type
      1 (HIV-1), HIV-1 infection gradually has become a treatable chronic disease.
      Successfully treated HIV-positive individuals can have a normal life expectancy.
      Hence, more and more HIV-1 discordant couples in Taiwan and the rest of the world
      are seeking fertility assistance. Pre-treatment of highly active antiretroviral
      therapy (HAART) combined with sperm washing and RT-polymerase chain reaction
      examination for HIV-1 viral load has become the standard procedure to assist them
      to conceive. However, in order to reduce the transmission risk to the lowest
      level for the couple and to diminish the cost of health care for the insurance
      institutes or government, in vitro fertilization (IVF)-intracytoplasmic sperm
      injection (ICSI) therapy provides the ideal solution for HIV-1 discordant couples
      with infected men. Intrauterine insemination (IUI) theoretically introduces more
      than 10(7) times of sperm counts or semen volume to uninfected women vs IVF-ICSI.
      However, since some regimens of HAART may significantly decrease the sperm
      motility, compared to IVF-ICSI, IUI only produces 1/5 to 1/2 pregnancy rates per
      cycle. Given the risk of seroconversion of HIV infection which actually happens
      after successful treatment, IVF-ICSI for these HIV-1 seropositive men is more
      cost-effective and should be the first line treatment for these cases. 

PMID- 25964880
TI  - Elevated homocysteine levels in human immunodeficiency virus-infected patients
      under antiretroviral therapy: A meta-analysis.
AB  - AIM: To evaluate the association between the levels of homocysteine (Hcy),
      folate, vitamin B12 in human immunodeficiency virus (HIV)-infected patients who
      were treated with antiretroviral therapy (ART) or not treated with ART. METHODS:
      The PubMed and Scielo databases were searched. Eligible studies regarding plasma
      Hcy level in HIV-infected patients were firstly identified. After careful
      analysis by two independent researches, the identified articles were included in
      the review according to two outcomes (1) Hcy, folate and vitamin B12 blood
      concentration in HIV-infected subjects vs health controls and; (2) Hcy blood
      concentration in HIV-infected subjects under ART vs not treated with ART. RevMan
      (version 5.2) was employed for data synthesis. RESULTS: A total of 12 studies
      were included in outcome 1 (1649 participants, 932 cases and 717 controls).
      Outcome 1 meta-analysis demonstrated higher plasma Hcy (2.05 umol/L; 95%CI: 0.10
      to 4.00, P < 0.01) and decreased plasma folate concentrations (-2.74 ng/mL;
      95%CI: -5.18 to -0.29, P < 0.01) in HIV-infected patients compared to healthy
      controls. No changes in vitamin B12 plasma concentration were observed between
      groups. All studies included in the outcome 2 meta-analysis (1167 participants;
      404 HIV-infected exposed to ART and 757 HIV-infected non-ART patients)
      demonstrated higher mean Hcy concentration in subjects HIV-infected under ART
      compared to non-ART HIV subjects (4.13 umol/L; 95%CI: 1.34 to 6.92, P < 0.01).
      CONCLUSION: This meta-analysis demonstrated that the levels of Hcy and folate,
      but not vitamin B12, were associated with HIV infection. In addition, Hcy levels
      were higher in HIV-infected patients who were under ART compared to HIV-infected
      patients who were not exposed to ART. Our results suggest that
      hyperhomocysteinemia should be included among the several important metabolic
      disturbances that are associated with ART in patients with HIV infection.

PMID- 25964881
TI  - Permcath catheter embolization: a case report.
AB  - INTRODUCTION: Nowadays, many types of intravascular devices and catheters are
      used in order to diagnose and treat diseases. Complications related to these
      instruments are the costs that doctors and patients have to pay to benefit from
      their advantages. Catheter embolization is one of these side effects. Patients
      with devices in their cardiopulmonary system are at risk for severe complications
      such as arrhythmias, pulmonary embolism, myocardial injuries, hemoptysis,
      thrombosis and perforation. CASE PRESENTATION: A 50-years-old woman, with a
      history of breast cancer, had a PermCath emplacement in right subclavian vein for
      a course of chemotherapy. The treatment for cancer seemed to be successful and
      the PermCath had remained in its position without complication, for a couple of
      years however, the catheter was founded broken and embolized to the right
      ventricle and the main left pulmonary artery, diagnosed by a chest X-ray study
      incidentally. CONCLUSIONS: It is better to remove the unused devices safely to
      prevent and decrease their possible complications.

PMID- 25964882
TI  - Locally advanced breast cancer - strategies for developing nations.

PMID- 25964883
TI  - Existential well-being and meaning making in the context of primary brain tumor:
      conceptualization and implications for intervention.
AB  - When faced with a significant threat to life, people tend to reflect more
      intensely upon existential issues, such as the meaning and purpose of one's life.
      Brain tumor poses a serious threat to a person's life, functioning, and
      personhood. Although recognized as an important dimension of quality of life,
      existential well-being is not well understood and reflects an overlooked area of
      support for people with brain tumor. This perspective article reviews the
      historical underpinnings of the concept of existential well-being and integrates
      this discussion with theoretical perspectives and research on meaning making and
      psychological adjustment to primary brain tumor. We then provide an overview of
      psychosocial support interventions for people with brain tumor and describe the
      findings of a recently published psychotherapy trial targeting existential well
      being. Overall, this article highlights the importance of assessing the
      existential support needs of people with primary brain tumor and their family
      members, and providing different avenues of support to facilitate the meaning
      making process across the illness trajectory. 

PMID- 25964884
TI  - Adolescent health: present status and its related programmes in India. Are we in
      the right direction?
AB  - Adolescence is a phase of rapid growth and development during which physical,
      physiological and behavioural changes occur. They constitute more than 1.2
      billion worldwide, and about 21% of Indian population. Morbidity and mortality
      occurring in this age group is mostly due to preventable causes. Young and
      growing children have poor knowledge and lack of awareness about physical and
      psychological changes that occurs during adolescence and the ill health affecting
      them. Existing Adolescent health programmes focus on rendering services like
      immunization, health education for sexual and reproductive health, nutritional
      education and supplementation, anemia control measures and counseling. Adolescent
      health programmes are fragmentary at present and there is no comprehensive
      programme addressing all the needs of adolescents. Access and availability of
      health care services are severely limited. Lack of accurate information, absence
      of proper guidance, parent's ignorance, lack of skills and insufficient services
      from health care delivery system are the major barriers. Interventions should
      focus on providing psychological and mental health services and behaviour change
      communication towards leading a healthy lifestyle, restricting advertisement
      related to junk food products, awareness creation about reproductive and sexual
      health, educating parents to prevent early marriage, teenage pregnancy and to
      counsel their children on nutrition and reproductive health. Universal coverage
      of Adolescent friendly clinics is highly recommended. To be cost effective, all
      health services addressing adolescent should come under single programme. This
      review is intended to create awareness among the stakeholders about the
      importance of strengthening adolescent health services in order to meet their
      felt needs. 

PMID- 25964885
TI  - Embryonal Rhabdomyosarcoma (RMS) of Retroperitoneum in Young Child.

PMID- 25964886
TI  - The role of Th1 and Th17 cells in glomerulonephritis.
AB  - CONTEXT: T helper (Th) cells as an important part of the immune is responsible
      for elimination of invading pathogens. But, if Th cell responses are not
      regulated effectively, the autoimmune diseases might develop. The Th17 subset
      usually produces interleukin-17A which in experimental models of organ-specific
      autoimmune inflammation is very important. EVIDENCE ACQUISITIONS: Directory of
      open access journals (DOAJ), Google Scholar, Embase, Scopus, PubMed and Web of
      Science have been searched. RESULTS: Fifty-six articles were found and searched.
      In the present review article, we tried to summarize the recently published data
      about characteristics and role of Th1 and Th17 cells and discuss in detail, the
      potential role of these T helpers immune responses in renal inflammation and
      renal injury, focusing on glomerulonephritis. Published papers in animal and
      human studies indicated that autoimmune diseases such as rheumatoid arthritis and
      multiple sclerosis, classically believed to be Th1-mediated, are mainly derived
      from a Th17 immune response. Identification of the Th17 subgroup has explained
      seemingly paradoxical observations and improved our understanding of immune
      mediated inflammatory responses. CONCLUSIONS: Secretion of IL-17A, as well as IL
      17F, IL-21, IL-22, suggests that Th17 subset may play a crucial role as a
      pleiotropic pro-inflammatory Th subset. There is experimental evidence to support
      the notion that Th1 and Th17 cells contribute to kidney injury in renal
      inflammatory diseases like glomerulonephritis.

PMID- 25964887
TI  - Gitelman's syndrome complicated by mild renal insufficiency and high anion gap
      acidosis; a rare presentation in a young female.
AB  - BACKGROUND: Gitelman's syndrome (GS) is a rare autosomal recessive renal tubular
      disorder that is characterized by episodic clinical manifestations and persistent
      biochemical abnormalities. The disorder manifests in adolescent or adult age and
      is characterized by transient episodes of muscle weakness and tetany. Its
      diagnosis requires a high index of suspicion and skillful interpretation of
      laboratory investigations. CASE PRESENTATION: We herein present a case of a 20
      year-old female patient who presented with generalized muscle weakness and mild
      renal insufficiency. Laboratory investigations revealed mild azotemia, high anion
      gap acidosis, hypokalemia, hypomagnesemia, and hypocalciuria. She recovered her
      renal functions and muscle power with appropriate management and is doing well
      seven months after her first presentation to our hospital. CONCLUSIONS: This case
      highlights the need to create high index of suspicion among the general
      practitioners about this syndrome and an early referral of such patients to
      nephrologists for an accurate diagnosis and appropriate management.

PMID- 25964888
TI  - Co-existence of thin basement membrane nephropathy with other glomerular
      pathologies; a single center experience.
AB  - BACKGROUND: The co-existence of thin basement membrane nephropathy (TBMN) and
      another glomerular pathology portends a worse prognosis than TBMN alone.
      OBJECTIVES: The purpose of our study was to investigate the prevalence of TBMN
      and associated glomerular pathologies at our institution. PATIENTS AND METHODS:
      We reviewed all renal biopsies performed at Saint Louis University hospital over
      a 7-year period. We excluded all post transplant biopsies, and biopsies showing
      diabetic glomerulopathy, membranoproliferative glomerulopathy, membranous
      glomerulopathy, and biopsies where no electron microscopy or immunofluorescent
      studies were done. All other biopsies were included. RESULTS: A total of 634
      biopsies were included in the study. The prevalence of TBMN was 47 (7.4%), of
      whom 17 (36.2%) had TBMN alone. In the remaining 30 (63.8%) patients TBMN was
      associated with other glomerular pathologies: IgAN 9 (19.1%) and FSGS 9 (19.1%).
      We found significantly higher prevalence of IgAN in patients with TBMN versus all
      biopsies (19.1% vs. 7.7%, respectively, P = 0.002). We found significant
      similarities in biopsy indications for TBMN and IgAN group. CONCLUSIONS: Around
      two thirds of the cases of TBMN were associated with other glomerular
      pathologies. The prevalence of IgAN, but not focal segmental glomerulosclerosis,
      was significantly higher in patients with TBMN as compared to the general renal
      biopsy specimens.

PMID- 25964889
TI  - Effect of pioglitazone therapy on high sensitive C-reactive protein and lipid
      profile in diabetic patients with renal transplantation; a randomize clinical
      trial.
AB  - BACKGROUND: Inflammation has a major role in disease lead to renal failure and
      diabetes mellitus, controlling inflammation in diabetic kidney receivers could
      decrease morbidity and mortality. OBJECTIVES: This study designed for evaluating
      the efficacy of pioglitazone on C-reactive protein and lipid profile in diabetic
      kidney transplant receivers. PATIENTS AND METHODS: In this double blinded
      clinical trial, 58 diabetic renal transplant receivers, in first month after
      transplantation, randomized into two groups; receiving insulin and pioglitazone
      (15 mg tablet daily, group A); and insulin and placebo (group B). Blood pressure,
      weight, body mass index (BMI) and laboratory data compared in before and after 4
      month treatment in two groups by SPSS. RESULTS: Fifty-eight patients with mean
      age of 44.15 +/- 2 years included. There were no significant difference between
      groups in demographic data and other baseline measured variables (P > 0.05) .The
      mean weigh and BMI were slightly increased in group A and decreased in group B.
      The mean hs-CRP was decreased 4.82 mg/dL in group A and 1.93 mg/dL in group B (P
      = 0.007). The mean total serum cholesterol was significantly decreased 34 mg/dL
      in group A and 18.07 mg/dL in group B (P = 0.027). The mean serum HDL-C was
      significantly increased 13.31 mg/dL in group A and 5.89 mg/dl in group B (P <
      0.001). CONCLUSIONS: Pioglitazone seems to be a safe drug for reducing serum
      lipids and CRP in kidney transplant receivers with diabetes mellitus in short
      term. Long term effect of this drug could be evaluated in future studies.

PMID- 25964890
TI  - Resolution of C1q deposition but not of the clinical nephrotic syndrome after
      immunomodulating therapy in focal sclerosis.
AB  - BACKGROUND: The natural evolution of C1q nephropathy (C1qNP) during
      immunosuppressive treatment is relatively little studied or understood. CASE
      PRESENTATION: A 30 year-old Caucasian female was referred to us for further
      management of biopsy-proven C1qNP and severe nephrotic syndrome. Serologic work
      up remained negative, including complement C3 and C4 levels and repeated testing
      for antinuclear antibodies. A renal biopsy revealed minimal change nephropathy
      vs. focal sclerosis on light microscopy and C1qNP on immunopathology. She has
      failed trials of high-dose oral prednisone, mycophenolate mofetil 1,500 mg twice
      a day and a subsequent regimen of monthly IV cyclophosphamide 750 mg * 9 cycles.
      She also received the maximum tolerated angiotensin-converting enzyme inhibitor
      and spironolactone therapy. Random urine protein-to-creatinine (UPC) ratio
      predicted proteinuria in the range between 5-35 gm/day, while serum creatinine
      rose progressively from 1.0 mg/dL to 1.4 mg/dL (to convert to MUmol/L, multiply
      by 88.4). A decision was made to repeat renal biopsy to reassess the underlying
      histology. The biopsy revealed focal sclerosis but no C1q deposition.
      CONCLUSIONS: Our case illustrates at least two points: first, an established
      pathologic diagnosis does not obviate the need for repeated renal biopsy later
      on, should diagnostic uncertainty persist. Second, histological diagnoses may
      evolve over time, especially in a patient receiving active and powerful immune
      modulating treatment. In our case, the clinical nephrosis did not change with
      immunosuppressive therapy while C1q deposition ceased, making this latter entity
      likely the immunologically mediated process.

PMID- 25964892
TI  - An Introduction to the Centers for Disease Control and Prevention's Efforts to
      Prevent Older Adult Falls.

PMID- 25964893
TI  - Falling for a balance partner.

PMID- 25964891
TI  - Hypoxia-inducible factor as an angiogenic master switch.
AB  - Hypoxia-inducible factors (HIFs) regulate the transcription of genes that mediate
      the response to hypoxia. HIFs are constantly expressed and degraded under
      normoxia, but stabilized under hypoxia. HIFs have been widely studied in
      physiological and pathological conditions and have been shown to contribute to
      the pathogenesis of various vascular diseases. In clinical settings, the HIF
      pathway has been studied for its role in inhibiting carcinogenesis. HIFs might
      also play a protective role in the pathology of ischemic diseases. Clinical
      trials of therapeutic angiogenesis after the administration of a single growth
      factor have yielded unsatisfactory or controversial results, possibly because the
      coordinated activity of different HIF-induced factors is necessary to induce
      mature vessel formation. Thus, manipulation of HIF activity to simultaneously
      induce a spectrum of angiogenic factors offers a superior strategy for
      therapeutic angiogenesis. Because HIF-2alpha plays an essential role in vascular
      remodeling, manipulation of HIF-2alpha is a promising approach to the treatment
      of ischemic diseases caused by arterial obstruction, where insufficient
      development of collateral vessels impedes effective therapy. Eukaryotic
      initiation factor 3 subunit e (eIF3e)/INT6 interacts specifically with HIF-2alpha
      and induces the proteasome inhibitor-sensitive degradation of HIF-2alpha,
      independent of hypoxia and von Hippel-Lindau protein. Treatment with eIF3e/INT6
      siRNA stabilizes HIF-2alpha activity even under normoxic conditions and induces
      the expression of several angiogenic factors, at levels sufficient to produce
      functional arteries and veins in vivo. We have demonstrated that administration
      of eIF3e/INT6 siRNA to ischemic limbs or cold-injured brains reduces ischemic
      damage in animal models. This review summarizes the current understanding of the
      relationship between HIFs and vascular diseases. We also discuss novel oxygen
      independent regulatory proteins that bind HIF-alpha and the implications of a new
      method for therapeutic angiogenesis using HIF stabilizers. 

PMID- 25964894
TI  - Translating fit and strong!: lessons learned and next steps.

PMID- 25964895
TI  - Evidence-based leadership council - a national collaborative.

PMID- 25964896
TI  - Examining Sustainability Factors for Organizations that Adopted Stanford's
      Chronic Disease Self-Management Program.
AB  - In 2006, funds were received to replicate Stanford's Chronic Disease Self
      Management Program (CDSMP) among eldercare providers in Honolulu. This case
      study, conducted 1 year after the close of the initial 3-year replication grant,
      explored factors for sustaining the delivery of CDSMP, with an aim to create
      guidelines for cultivating sustainability. Face-to-face semi-structured
      interviews were conducted with one representative from each of eight eldercare
      agencies, with the representative specified by the agency. Representatives
      discussed the presence and strength (low, medium, or high) of sustainability
      factors, including readiness, champions, technical assistance, perceived fit of
      CDSMP with their agency, CDSMP modifiability, perceived benefits of CDSMP, and
      other. Only three of the eight agencies (38%) were still offering CDSMP by the
      end of 2010. Agencies who sustained CDSMP rated higher on all sustainability
      factors compared to those that did not sustain the program. Additional factors
      identified by representatives as important were funding and ongoing access to
      pools of elders from which to recruit program participants. When replicating
      evidence-based programs, sustainability factors must be consciously nurtured. For
      example, readiness must be cultivated, multiple champions must be developed,
      agencies must be helped to modify the program to best fit their clientele,
      evaluation findings demonstrating program benefit should be shared, and linkages
      to funding may be needed. 

PMID- 25964897
TI  - Perceived Utility of the RE-AIM Framework for Health Promotion/Disease Prevention
      Initiatives for Older Adults: A Case Study from the U.S. Evidence-Based Disease
      Prevention Initiative.
AB  - Dissemination and implementation (D&I) frameworks are increasingly being promoted
      in public health research. However, less is known about their uptake in the
      field, especially for diverse sets of programs. Limited questionnaires exist to
      assess the ways that frameworks can be utilized in program planning and
      evaluation. We present a case study from the United States that describes the
      implementation of the RE-AIM framework by state aging services providers and
      public health partners and a questionnaire that can be used to assess the utility
      of such frameworks in practice. An online questionnaire was developed to capture
      community perspectives about the utility of the RE-AIM framework. Distributed to
      project leads in 27 funded states in an evidence-based disease prevention
      initiative for older adults, 40 key stakeholders responded representing a 100%
      state-participation rate among the 27 funded states. Findings suggest that there
      is perceived utility in using the RE-AIM framework when evaluating grand-scale
      initiatives for older adults. The RE-AIM framework was seen as useful for
      planning, implementation, and evaluation with relevance for evaluators,
      providers, community leaders, and policy makers. Yet, the uptake was not
      universal, and some respondents reported difficulties in use, especially adopting
      the framework as a whole. This questionnaire can serve as the basis to assess
      ways the RE-AIM framework can be utilized by practitioners in state-wide D&I
      efforts. Maximal benefit can be derived from examining the assessment of RE-AIM
      related knowledge and confidence as part of a continual quality assurance
      process. We recommend such an assessment be performed before the implementation
      of new funding initiatives and throughout their course to assess RE-AIM uptake
      and to identify areas for technical assistance. 

PMID- 25964898
TI  - "Stepping on": stepping over the chasm from research to practice.

PMID- 25964899
TI  - Translation of the otago exercise program for adoption and implementation in the
      United States.
AB  - BACKGROUND: The Otago Exercise Program (OEP) is an evidence-based fall prevention
      program developed, evaluated, and disseminated in New Zealand. The program was
      designed for delivery in the home by physical therapists (PTs). It was not known
      if American PTs would require additional training and resources to adopt the OEP.
      This article describes the process of translating the OEP for dissemination in
      the US. Processes included reviewing and piloting the New Zealand training
      materials to identify implementation challenges, updating training materials to
      be consistent with American physical therapy practices, piloting the updated
      training materials in an online format, and determining if the online format
      reached the target PT audience. METHODS - PROCESS ACTIVITIES: The New Zealand
      manual was reviewed by expert American PTs and a training webinar was piloted
      with 56 American PTs. Feedback suggested that the program itself was understood
      by PTs, but training materials required modification related to documentation and
      reimbursement policies. Additional content was developed and integrated into an
      online training module. The online training was piloted and then deemed adequate
      by seven PT subject matter experts. The online training was launched in March
      2013. Demographic and practice data were collected to characterize the PTs
      attending the online training as well as perceived barriers and facilitators to
      implementation (n = 522). Perceived facilitators include the effectiveness of the
      OEP to facilitate adoption, but the lack of agency support, billing and
      reimbursement challenges pose a significant barrier to OEP implementation.
      CONCLUSION: The OEP required additional information to facilitate adoption by
      American PTs. Online training that specifically targets PTs appears to
      effectively reach the target audience and be well received by participants. More
      research is required to determine the impact of online training on a PT's
      adoption and implementation of this material into their practice.

PMID- 25964900
TI  - Factors associated with Hispanic adults attending spanish-language disease self
      management program workshops and workshop completion.
AB  - Many factors influence ways in which middle-aged and older Hispanic adults prefer
      to receive health-related information. While Spanish-language disease management
      programs are increasingly offered in community and healthcare settings, less is
      known about their utilization among the Hispanic population. This study aimed to
      identify participant and workshop factors associated with middle-aged and older
      Hispanic adults attending Spanish-language disease self-management program
      workshops and receiving the recommended intervention dose (i.e., successful
      workshop completion is defined as attending four or more of the six workshop
      sessions). Data were analyzed from 12,208 Hispanic adults collected during a
      national dissemination of the Stanford suite of Chronic Disease Self-Management
      Education (CDSME) programs spanning 45 states, the District of Columbia, and
      Puerto Rico. Two logistic regression analyses were performed. Over 65% of
      participants attended Spanish-language workshops, and 78.3% of participants
      successfully completed workshops. Relative to participants in English-language
      workshops, participants who attended Spanish-language CDSME workshops were more
      likely to successfully complete workshops, as were those aged 80 years and older,
      females, and those who lived alone. Participants who were aged 50-79 years and
      female were significantly more likely to attend Spanish-language workshops than
      their counterparts under age 50. Conversely, those with more chronic conditions
      were less likely to attend Spanish-language workshops. Those who attended
      workshops with more participants and where the Hispanic population was less
      affluent were more likely to attend Spanish-language workshops. This study
      provides insight into Spanish-language CDSME program recruitment and utilization
      with implications for program adoption in underserved Hispanic community
      settings. 

PMID- 25964902
TI  - Implementing chronic disease self-management approaches in australia and the
      United kingdom.

PMID- 25964901
TI  - National dissemination of multiple evidence-based disease prevention programs:
      reach to vulnerable older adults.
AB  - Older adults, who are racial/ethnic minorities, report multiple chronic
      conditions, reside in medically underserved rural areas, or have low incomes
      carry a high burden of chronic illness but traditionally lack access to disease
      prevention programs. The Chronic Disease Self-Management Program (CDSMP), A
      Matter of Balance/Volunteer Lay Leader (AMOB/VLL), and EnhanceFitness (EF) are
      widely disseminated evidence-based programs (EBP), but the extent to which they
      are simultaneously delivered in communities to reach vulnerable populations has
      not been documented. We conducted cross-sectional analyses of three EBP
      disseminated within 27 states throughout the United States (US) (2006-2009) as
      part of the Administration on Aging (AoA) Evidence-Based Disease and Disability
      Prevention Initiative, which received co-funding from the Atlantic
      Philanthropies. This study measures the extent to which CDSMP, AMOB/VLL, and EF
      reached vulnerable older adults. It also examines characteristics of communities
      offering one of these programs relative to those simultaneously offering two or
      all three programs. Minority/ethnic participants represented 38% for CDSMP, 26%
      for AMOB/VLL, and 43% for EF. Rural participation was 18% for CDSMP, 17% for
      AMOB/VLL, and 25% for EF. Those with comorbidities included 63.2% for CDSMP,
      58.7% for AMOB/VLL, and 63.6% for EF while approximately one-quarter of
      participants had incomes under $15,000 for all programs. Rural areas and health
      professional shortage areas (HPSA) tended to deliver fewer EBP relative to urban
      areas and non-HPSA. These EBP attract diverse older adult participants. Findings
      highlight the capability of communities to serve potentially vulnerable older
      adults by offering multiple EBP. Because each program addresses unique issues
      facing this older population, further research is needed to better understand how
      communities can introduce, embed, and sustain multiple EBP to ensure widespread
      access and utilization, especially to traditionally underserved subgroups. 

PMID- 25964903
TI  - Village or tribe? Expectations, roles, and responsibilities for effective fall
      prevention efforts.

PMID- 25964904
TI  - Adoption of Evidence-Based Health Promotion Programs: Perspectives of Early
      Adopters of Enhance((r))Fitness in YMCA-Affiliated Sites.
AB  - PURPOSE: To identify facilitators and barriers among early adopters of
      Enhance((r))Fitness (EF), in Young Men's Christian Association-affiliated (Y
      affiliated) sites from the perspective of program staff. EF is an evidence-based
      group exercise program for seniors. METHODS: This qualitative study used semi
      structured phone interviews with 15 staff members representing 14 Y-affiliated
      sites. Interviews were digitally recorded, transcribed, and analyzed using
      qualitative content analysis informed by the RE-AIM framework. FINDINGS: Staff
      were, on average, 48.7 years old (SD 13.5) and had been involved with EF for 5.2
      years (SD 3.1). Key themes related to facilitating adoption of EF were: match
      with the Y mission, support from different organizational levels, match between
      the target population need and EF, initial and on-going financial support,
      presence of champions, novelty of EF, an invitation to partner with a community
      based organization to offer EF, and program-specific characteristics of EF. Key
      themes related to barriers interfering with EF adoption included competing
      organizational programs and space limitations, limited resources and expertise,
      and costs of offering the program. IMPLICATIONS: Our findings identify the types
      of organizational support needed for adoption of evidence-based health promotion
      programs like EF. Recommendations for practice, research, and policy based on the
      findings, including assessing organizational readiness, researching late
      adopters, and developing revenue streams, may help facilitate program adoption.
      Packaging and sharing these practical recommendations could help community-based
      agencies and nationally networked organizations facilitate adoption of EF and
      other evidence-based programs.

PMID- 25964905
TI  - Fit & strong! Promotes physical activity and well-being in older cancer
      survivors.
AB  - INTRODUCTION: Physical activity reduces fatigue and depression while improving
      quality of life in cancer survivors. Exercise is generally considered safe and is
      recommended to survivors of all ages. Despite the high prevalence of cancer in
      the elderly, few studies address physical activity interventions targeting this
      older population. Fit & Strong! is an evidence-based physical activity program
      shown to improve level of physical activity, exercise-self-efficacy, and mood in
      older adults with osteoarthritis. This study tests the feasibility and short-term
      impact of the Fit & Strong! exercise program adapted for older cancer survivors.
      METHODS: Participants were cancer survivors at least 50 years of age who were not
      on active treatment with intravenous chemotherapy or radiation. They participated
      in the 8-week Fit & Strong! program, which included three 90-min sessions per
      week; 60 min of group physical activity and 30 min of education. Education on
      osteoarthritis was removed from the Fit & Strong! program and replaced with
      relevant topics on cancer survivorship issues. Feasibility was measured by the
      ability to recruit and retain older cancer survivors. Pre and post-intervention
      surveys evaluated the effect of the intervention on physical activity and quality
      of life. RESULTS: The study enrolled 72 cancer survivors to participate in an 8
      week exercise program. The mean age of participants was 70. Over two-thirds (68%)
      of participants completed the program and with a mean attendance rate of 75% (18
      of 24 sessions). No safety issues occurred. Improvements from baseline to post
      intervention were observed for self-reported minutes of physical activity per
      week, self-efficacy for aerobic exercise, and symptoms related to depression and
      anxiety. CONCLUSION: This study was successful in recruiting and retaining a
      population of older cancer survivors to participate in a group exercise program.
      Significant improvement in level of physical activity and mood suggests this
      evidence-based physical activity intervention can be adapted to promote health
      benefits in cancer survivors. Additional studies are necessary to confirm
      efficacy and assess long-term benefits.

PMID- 25964906
TI  - The reach of chronic-disease self-management education programs to rural
      populations.
AB  - This study assessed the sociodemographic characteristics of rural residents who
      participated in chronic-disease self-management education (CDSME) program
      workshops and the extent to which CDSME programs were utilized by those with
      limited access to health care services. We analyzed data from the first 100,000
      adults who attended CDSME program workshops during a national dissemination
      spanning 45 states, the District of Columbia, and Puerto Rico. Approximately 24%
      of participants lived in rural areas. Overall, 42% of all participants were
      minorities; urban areas reached more minority participants (48%) than rural areas
      (25%). The average age of participants was high in rural (age, MU = 66.1) and
      urban (age, MU = 67.3) areas. In addition, the average number of chronic
      conditions was higher (p < 0.01) in rural (MU = 2.6 conditions) versus urban (MU
      = 2.4 conditions) areas. Successful completion of CDSME programs (i.e., attending
      four or more of the six workshop sessions) was higher (p < 0.01) in rural versus
      urban areas (78% versus 77%). Factors associated with higher likelihood of
      successful completion of CDSME programs included being Black (OR = 1.25) versus
      White and living in rural (versus urban) areas (OR = 1.09). Factors associated
      with lower likelihood of successful completion included being male (OR = 0.92)
      and residing in a primary care Health Professional Shortage Area or HPSA (versus
      a non-HPSA) (OR = 0.93). Findings highlight the capability of CDSME programs to
      reach rural residents, yet dissemination efforts can be further enhanced to
      ensure minorities and individuals in a HPSA utilize this program. Tailored
      strategies are needed to increase participant recruitment and retention in rural
      areas to overcome traditional barriers to health service access. 

PMID- 25964907
TI  - Chronic Disease Self-Management Education (CDSME) Program Delivery and Attendance
      among Urban-Dwelling African Americans.
AB  - BACKGROUND: Older African Americans carry a disproportionate share of chronic
      diseases. The purpose of this study was to identify the characteristics of urban
      dwelling African Americans with chronic disease participating in Chronic Disease
      Self-Management Education (CDSME) programs and to examine factors related to
      successful program completion (i.e., attending at least four of the six
      sessions). METHODS: Data were analyzed from 11,895 African Americans who attended
      a CDSME program at one of the five leading delivery sites (i.e., senior center,
      health care organization, residential facility, community location, faith-based
      organization). Logistic regression analyses were used to assess the associations
      of demographic, delivery site, and neighborhood characteristics with CDSME
      program successful completion. RESULTS: Approximately, half of the African
      American participants were aged 65-79 years, 83% were female, and 92% lived
      alone. Approximately, 44% of participants had three or more chronic conditions
      and 35% resided in an impoverished area (i.e., 200% below federal poverty level).
      Successful completion of the CDSME program was associated with being between the
      ages of 50-64 and 65-79 years, being female, living alone, living in an
      impoverished community, and attending a CDSME program at a residential facility
      or community center. CONCLUSION: Findings highlight the unique patterns of
      attendance and delivery within the context of self-management interventions among
      this unique and traditionally underserved target population. Understanding such
      patterns can inform policy and practice efforts to engage more organizations in
      urban areas to increase CDSME program adoption. Particularly, employing
      strategies to implement CDSME programs across all delivery site types may
      increase reach to African American participants.

PMID- 25964908
TI  - Linking evidence-based program participant data with medicare data: the
      consenting process and correlates of retrospective participant consents.
AB  - As part of a nation-wide study of the Chronic Disease Self-Management Program
      (National Study), older participants were asked to consent to have their Medicare
      data matched with study data. This provided an opportunity to examine the
      consenting process and compare consenters, refusers, and non-responders. We
      compared the three groups on a large number of variables. These included
      demographic, National Study participation, health indicator, health behavior, and
      health-care utilization variables. We assessed differences in 6-month change
      scores for time-varying variables. We also examined whether asking participants
      to consent prior to the final questionnaire impacted completion of that
      questionnaire. Of 616 possible participants, 42% consented, 44% refused, and 14%
      failed to respond. Differences by ethnicity were found, with Hispanics more
      likely to consent. There was a consistent tendency for those who participated
      most in the National Study to consent. With the exception of number of chronic
      diseases, there was no evidence of health indicators or health behaviors being
      associated with consenting. Participants with more physician visits and more
      nights in the hospital were also more likely to consent. Those asked to consent
      before the 12-month follow-up questionnaire were less likely to complete that
      questionnaire than those who were asked after. Fewer than half consented to link
      to their Medicare data. The greater willingness to consent by those who
      participated most suggests that willingness to consent may be part of program
      engagement. Consenters had more diseases, more MD visits, and more nights in the
      hospital, suggesting that greater contact with the medical system may be
      associated with willingness to consent. This indicates that examinations of
      Medicare data based only on those willing to consent could introduce bias. Asking
      for consent appears to reduce participation in the larger study. 

PMID- 25964909
TI  - Chronic disease self-management program in the workplace: opportunities for
      health improvement.
AB  - Disease management is becoming increasingly important in workplace health
      promotion given the aging workforce, rising chronic disease prevalence, and needs
      to maintain a productive and competitive American workforce. Despite the
      widespread availability of the Chronic Disease Self-Management Program (CDSMP),
      and its known health-related benefits, program adoption remains low in workplace
      settings. The primary purpose of this study is to compare personal and delivery
      characteristics of adults who attended CDSMP in the workplace relative to other
      settings (e.g., senior centers, healthcare organizations, residential
      facilities). This study also contrasts characteristics of CDSMP workplace
      participants to those of the greater United States workforce and provides
      recommendations for translating CDSMP for use in workplace settings. Data were
      analyzed from 25,664 adults collected during a national dissemination of CDSMP.
      Only states and territories that conducted workshops in workplace settings were
      included in analyses (n = 13 states and Puerto Rico). Chi-squared tests and t
      tests were used to compare CDSMP participant characteristics by delivery site
      type. CDSMP workplace participant characteristics were then compared to reports
      from the United States Bureau of Labor Statistics. Of the 25,664 CDSMP
      participants in this study, 1.7% (n = 435) participated in workshops hosted in
      worksite settings. Compared to CDSMP participants in non-workplace settings,
      workplace setting participants were significantly younger and had fewer chronic
      conditions. Differences were also observed based on chronic disease types. On
      average, CDSMP workshops in workplace settings had smaller class sizes and
      workplace setting participants attended more workshop sessions. CDSMP
      participants in workplace settings were substantially older and a larger
      proportion were female than the general United States workforce. Findings
      indicate opportunities to translate CDSMP for use in the workplace to reach new
      target audiences. 

PMID- 25964910
TI  - Implementing a chronic disease self-management program into china: the happy life
      clubTM.
AB  - China is experiencing population aging, increased prevalence of chronic diseases,
      and reductions in the frequency of healthy lifestyle behaviors. In response to
      these significant transitions, China is implementing major reforms in health care
      services with a focus on strengthening primary health care. In this paper, we
      describe a 12-month diabetes management program, the Happy Life ClubTM (HLCTM),
      implemented in a primary health care setting in Beijing, that uses doctor and
      nurse health coaches trained in behavior change techniques and motivational
      interviewing (MI). This paper reports the results of this pilot study and
      discusses issues involved in the implementation of Chronic Diseases Self
      Management Programs in China. The intervention group showed improvements in HbA1c
      levels at 6 months and both the control and intervention groups showed reductions
      in waist circumference over time. Systolic blood pressure improved over time in
      the intervention group. The intervention group showed improvement in quality of
      life across the intervention period and both groups showed decreases in
      psychological distress across the intervention. Doctor visits increased between
      baseline and 6 months, but there was no change in doctor visits between 6 and 12
      months for both groups. The effects were modest, and further investigations are
      required to evaluate the long-term impact of health coach approaches in China. 

PMID- 25964911
TI  - Effects of an Evidence-Based Falls Risk-Reduction Program on Physical Activity
      and Falls Efficacy among Oldest-Old Adults.
AB  - PURPOSE OF THE STUDY: The current study was designed to examine changes in falls
      efficacy and physical activities among oldest-old and young-old participants in a
      falls risk-reduction program called a matter of balance/volunteer lay leader
      model. DESIGN AND METHODS: An oldest-old group (aged 85 years and older; n = 260)
      and a young-old group (aged between 65 and 84 years old; n = 1,139) in Texas with
      both baseline and post-intervention measures were included. Changes in Falls
      Efficacy Scale scores and weekly physical activity levels were examined from
      baseline to post-intervention. Repeated measures analysis of covariance were
      employed to assess program effects on falls efficacy. RESULTS: Results showed
      significant changes in falls efficacy from baseline to post-intervention, as well
      as a significant interaction effect between time (baseline and post-intervention)
      and physical activity on falls efficacy. IMPLICATIONS: Findings from this study
      imply the effectiveness of evidence-based programs for increasing falls efficacy
      in oldest-old participants. Future implications for enhancing physical activities
      and reducing fear of falling for oldest-old adults are discussed.

PMID- 25964912
TI  - Translation of fit & strong! For middle-aged and older adults: examining
      implementation and effectiveness of a lay-led model in central Texas.
AB  - The Fit & Strong! program is an evidence-based, multi-component program promoting
      physical activity among older adults, particularly those suffering from lower
      extremity osteoarthritis. The primary purpose of the study is to examine if the
      Fit & Strong! program translated into a lay-leader model can produce comparable
      outcomes to the original program taught by physical therapists and/or certified
      exercise instructors. A single-group, pre-post study design was employed, and
      data were collected at the baseline (n = 136 participants) and the intervention
      conclusion (n = 71) with both baseline and post-intervention data. The
      measurements included socio-demographic information, health- and behavior-related
      information, and health-related quality of life. Various statistical tests were
      used for the program impact analysis and examination of the association between
      participant characteristics and program completion. As in the original study,
      there were statistically significant (p < 0.05) improvements in self-efficacy for
      exercise, aerobic capacity, joint stiffness, level of energy, and amount and
      intensity of physical activities. The odds of completing the program were
      significantly lower for the participants from rural areas and those having
      multiple chronic conditions. Successful adaptation of the Fit & Strong! program
      to a lay-leader model can increase the likelihood of program dissemination by
      broadening the selection pool of instructors and, hence, reducing the potential
      issue of resource limitation. However, high program attrition rates (54.1%)
      emphasize the importance of adopting evidence-based strategies for improving the
      retention of the participants from rural areas and those with multiple chronic
      conditions. 

PMID- 25964913
TI  - Community-based wellness and prevention programs: the role of medicare.

PMID- 25964914
TI  - Foundation engagement in healthy aging initiatives and evidence-based programs
      for older adults.

PMID- 25964915
TI  - Public health system perspective on implementation of evidence-based fall
      prevention strategies for older adults.

PMID- 25964916
TI  - Building the older adult fall prevention movement - steps and lessons learned.
AB  - BACKGROUND: Falls are the leading cause of older adult injuries and injury
      related deaths. Until 2004, the growing public health issue of older adult falls
      received little national attention. To elevate and focus on the issue, the
      National Council on Aging launched the Falls Free((r)) Initiative, a group of
      national and state agencies working collaboratively to address older adult falls
      with evidence-based solutions. Since then, attention to older adult falls has
      gained significant momentum. PURPOSE: To describe the steps taken to create the
      momentum around fall prevention and lessons learned that could be applied to
      supporting other older adult health-related issues. METHOD/OBJECTIVES: The Falls
      Free((r)) Initiative took key steps to promote the older adult falls prevention
      movement, including initiating organized advocacy and supporting the development
      of state coalitions through increasing awareness of the issue, promoting evidence
      based programs, instituting evaluation, implementing systems change, and
      providing tailored technical assistance. RESULTS: Through the support of the
      Falls Free((r)) Initiative and many partners, advocacy efforts have increased
      federal funding for fall prevention, the majority of states have fall prevention
      coalitions, and thousands of stakeholders are now engaged in fall prevention.
      Select lessons learned include leveraging compelling data, choosing passionate
      leaders for the movement, aligning the cause with partner missions, and being
      inclusive of all stakeholders. CONCLUSION: Although much progress has been made
      in the fall prevention movement, the issue is growing along with the aging
      population. Efforts must continue to gain support from all affected stakeholders
      to reduce older adult falls and fall-related injuries.

PMID- 25964917
TI  - Development and Evaluation of a Fidelity Instrument for PEARLS.
AB  - PURPOSE: This manuscript describes the development and the preliminary evaluation
      of a fidelity instrument for the Program for Encouraging Active and Rewarding
      Lives (PEARLS), an evidence-based depression care management (DCM) program. The
      objective of the study was to find an effective, practical, multidimensional
      approach to measure fidelity of PEARLS programs to the original, research-driven
      PEARLS protocol in order to inform program implementation at various settings
      nationwide. METHODS: We conducted key informant interviews with PEARLS
      stakeholders, and held focus groups with former PEARLS clients, to identify core
      program components. These components were then ranked using a Q-sort process, and
      incorporated into a brief instrument. We tested the instrument at two time points
      with PEARLS counselors, other DCM program counselors, and non-DCM program
      counselors (n = 56) in six states. Known-groups method was used to compare
      findings from PEARLS programs, other DCM programs, and non-DCM programs. We asked
      supervisors of the counselors to complete the fidelity instrument on behalf of
      their counselors to affirm the validity of the results. We examined the
      association of PEARLS program fidelity with individual client outcomes. RESULTS:
      Program for Encouraging Active and Rewarding Lives providers reported the highest
      fidelity scores compared to DCM program providers and non-DCM program providers.
      The sample size was too small to yield significant results on the comparison
      between counselor experience and fidelity. Scores varied between PEARLS
      counselors and their supervisors. PEARLS program fidelity was not significantly
      correlated with client outcomes, suggesting that other implementation factors may
      have influenced the outcomes and/or that the instrument needs refinement.
      CONCLUSION: Our findings suggest that providers may be able to use the instrument
      to assess PEARLS program fidelity in various settings across the country.
      However, more rigorous research is needed to evaluate instrument effectiveness.

PMID- 25964918
TI  - The role of session zero in successful completion of chronic disease self
      management program workshops.
AB  - BACKGROUND: The Chronic Disease Self-Management Program (CDSMP) has been widely
      disseminated among various racial and ethnic populations. In addition to the six
      required CDSMP workshop sessions, the delivery sites have the option to offer a
      Session Zero (or zero class), an information session offered prior to Session One
      as a marketing tool. Despite assumptions that a zero class is helpful, little is
      known about the prevalence of these additional sessions or their impact on
      retaining participants in CDSMP workshops. This study aims to describe the
      proportion of CDSMP workshops that offered Session Zero and examine the
      association between Session Zero and workshop completion rates. METHODS: Data
      were analyzed from 80,987 middle-aged and older adults collected during a two
      year national dissemination of CDSMP. Generalized estimating equation regression
      analyses were conducted to assess the association between Session Zero and
      successful workshop completion (attending four or more of the six workshop
      sessions). RESULTS: On average, 21.04% of the participants attended workshops
      that offered Session Zero, and 75.33% successfully completed the CDSMP workshop.
      The participants of the workshops that offered Session Zero had significantly
      higher odds of completing CDSMP workshops than those who were not offered Session
      Zero (OR = 1.099, P = <0.001) after controlling for participants' demographic
      characteristics, race, ethnicity, living status, household income, number of
      chronic conditions, and workshop delivery type. CONCLUSION: As one of the first
      studies reporting the importance of an orientation session for participant
      retention in chronic disease management intervention projects, our findings
      suggest offering an orientation session may increase participant retention in
      similar translational efforts.

PMID- 25964919
TI  - Setting the stage: measure selection, coordination, and data collection for a
      national self-management initiative.
AB  - This paper describes the history and rationale behind the development of a
      centralized data collection system for the national rollout of the Chronic
      Disease Self-Management Program (CDSMP) through the American Recovery and
      Reinvestment Act of 2009 Communities Putting Prevention to Work: CDSMP
      initiative. In addition to justifying the need for solutions to the burgeoning
      burden of chronic disease in the United States, this paper provides details about
      CDSMP and related self-management education programs, including their structure,
      facilitator training, and effectiveness. These topics set the stage for the
      processes and procedures to create and manage the database for use at the
      national, state, and local levels. Furthermore, this paper describes the
      processes related to selecting variables, coordinating data collection, and
      utilizing data to inform research and policy. 

PMID- 25964920
TI  - Developing an evidence-based fall prevention curriculum for community health
      workers.
AB  - This perspective paper describes processes in the development of an evidence
      based fall prevention curriculum for community health workers/promotores (CHW/P)
      that highlights the development of the curriculum and addresses: (1) the need and
      rationale for involving CHW/P in fall prevention; (2) involvement of CHW/P and
      content experts in the curriculum development; (3) best practices utilized in the
      curriculum development and training implementation; and (4) next steps for
      dissemination and utilization of the CHW/P fall prevention curriculum. The
      project team of CHW/P and content experts developed, pilot tested, and revised
      bilingual in-person training modules about fall prevention among older adults.
      The curriculum incorporated the following major themes: (1) fall risk factors and
      strategies to reduce/prevent falls; (2) communication strategies to reduce risk
      of falling and strategies for developing fall prevention plans; and (3) health
      behavior change theories utilized to prevent and reduce falls. Three separate
      fall prevention modules were developed for CHW/P and CHW/P Instructors to be used
      during in-person trainings. Module development incorporated a five-step process:
      (1) conduct informal focus groups with CHW/P to inform content development; (2)
      develop three in-person modules in English and Spanish with input from content
      experts; (3) pilot-test the modules with CHW/P; (4) refine and finalize modules
      based on pilot-test feedback; and (5) submit modules for approval of continuing
      education units. This project contributes to the existing evidence-based
      literature by examining the role of CHW/P in fall prevention among older adults.
      By including evidence-based communication strategies such as message tailoring,
      the curriculum design allows CHW/P to personalize the information for
      individuals, which can result in an effective dissemination of a curriculum that
      is evidence-based and culturally appropriate. 

PMID- 25964922
TI  - Meeting the challenge of cancer survivorship in public health: results from the
      evaluation of the chronic disease self-management program for cancer survivors.
AB  - INTRODUCTION: Self-management has been identified as an important opportunity to
      improve health outcomes among cancer survivors. However, few evidence-based
      interventions are available to meet this need. METHODS: The effectiveness of an
      adapted version of the Chronic Disease Self-Management Program for cancer
      survivors called Cancer Thriving and Surviving was evaluated in a randomized
      trial. Outcomes were assessed at baseline and 6-months post program via written
      survey among 244 participants in Colorado. Repeated measures analysis was used to
      analyze pre/post program change. RESULTS: Statistically significant improvement
      was observed among those in the intervention in the following outcomes: Provider
      communication (+16.7% change); depression (-19.1%); energy (+13.8%); sleep (
      24.9%) and stress-related problems (-19.2%); change over time was also observed
      in the controls for energy, sleep, and stress-related outcomes though to a lesser
      degree. Effect sizes of the difference in change over time observed indicate a
      net beneficial effect for provider communication (0.23); and decreases in
      depression (-0.18); pain (-0.19); problems related to stress (-0.17); and sleep (
      0.20). CONCLUSION: Study data suggest that the self-management support from
      adaptation of the CDSMP can reach and appeal to cancer survivors, improves common
      concerns in this population, and can fill an important gap in meeting the ongoing
      need for management of post-diagnosis issues in this growing segment of the U.S.
      population.

PMID- 25964923
TI  - National dissemination of chronic disease self-management education programs: an
      incremental examination of delivery characteristics.
AB  - With a near 20-year developmental history as an evidence-based program, the suite
      of Chronic Disease Self-Management Education (CDSME) programs were selected in
      2010 for grand-scale dissemination in a federally supported initiative to improve
      the health of older Americans. The primary charge of this national effort was to
      establish a sustainable program delivery system for empowering American adults
      with one or more chronic conditions to better manage their health. The current
      study focused on a series of dissemination and implementation science research
      questions to: (1) examine the geographic distribution of participation in this
      initiative across the Unites States; (2) describe workshop characteristics
      engaged to reach program participants in various settings; and (3) describe
      personal characteristics of the first 100,000 participants. Each subsequent
      entering cohort was descriptively examined to indicate whether there was
      constancy or change in delivery sites and populations reached over time. Findings
      show a strengthening of the workshop delivery infrastructure in that it took 9.4
      months to reach the first 25,000 participants in 853 counties compared to 5.4
      months to reach the last 25,000 participants in 1,109 counties. The workshop
      delivery characteristics and participant characteristics remained relatively
      consistent across increments of 25,000 participants reached, although general
      trends were observed for some variables. For example, after reaching the first
      25,000 participants, subsequent groups of 25,000 participants were reached more
      quickly. Additionally, workshops were increasingly delivered in ZIP Codes with
      higher percentages of families residing below the federal poverty line. As more
      participants were reached, more participants with chronic conditions were
      enrolled. This national translational study illustrates the rapid expansion of
      CDSME programs throughout the United States and capability to reach diverse
      populations in a variety of settings. 

PMID- 25964924
TI  - Fall prevention in community settings: results from implementing stepping on in
      three States.
AB  - Stepping On is a community-based intervention that has been shown in a randomized
      controlled trial to reduce fall risk. The Wisconsin Institute for Healthy Aging
      adapted Stepping On for use in the United States and developed a training
      infrastructure to enable dissemination. The purpose of this study is to: (1)
      describe the personal characteristics of Stepping On participants; (2) quantify
      participants' functional and self-reported health status at enrollment, and (3)
      measure changes in participants' functional and self-reported health status after
      completing the program. Both survey and observed functional status [timed up and
      go (TUG) test] data were collected between September 2011 and December 2013 for
      366 participants enrolled in 32 Stepping On programs delivered in Colorado, New
      York, and Oregon. Paired t-tests and general estimating equations models adjusted
      for socio-demographic factors were performed to assess changes over the program
      period. Among the 266 participants with pre-post survey data, the average
      participant age was 78.7 (SD +/- 8.0) years. Most participants were female
      (83.4%), white (96.9%), and in good health (49.4%). The TUG test scores decreased
      significantly (p < 0.001) for all 254 participants with pre-post data. The change
      was most noticeable among high risk participants where TUG time decreased from
      17.6 to 14.4 s. The adjusted odds ratio of feeling confident about keeping from
      falling was more than three times greater after completing Stepping On. Further,
      the adjusted odds ratios of reporting "no difficulty" for getting out of a
      straight back chair increased by 89%. Intended for older adults who have fallen
      in the past or are afraid of falling, Stepping On has the potential to reduce the
      frequency and burden of older adult falls. 

PMID- 25964921
TI  - Effect of physical activity, social support, and skills training on late-life
      emotional health: a systematic literature review and implications for public
      health research.
AB  - PURPOSE: Given that emotional health is a critical component of healthy aging, we
      undertook a systematic literature review to assess whether current interventions
      can positively affect older adults' emotional health. METHODS: A national panel
      of health services and mental health researchers guided the review. Eligibility
      criteria included community-dwelling older adult (aged >= 50 years) samples,
      reproducible interventions, and emotional health outcomes, which included
      multiple domains and both positive (well-being) and illness-related (anxiety)
      dimensions. This review focused on three types of interventions - physical
      activity, social support, and skills training - given their public health
      significance and large number of studies identified. Panel members evaluated the
      strength of evidence (quality and effectiveness). RESULTS: In all, 292 articles
      met inclusion criteria. These included 83 exercise/physical activity, 25 social
      support, and 40 skills training interventions. For evidence rating, these 148
      interventions were categorized into 64 pairings by intervention type and
      emotional health outcome, e.g., strength training targeting loneliness or social
      support to address mood. 83% of these pairings were rated at least fair quality.
      Expert panelists found sufficient evidence of effectiveness only for skills
      training interventions with health outcomes of decreasing anxiety and improving
      quality of life and self-efficacy. Due to limitations in reviewed studies, many
      intervention-outcome pairings yielded insufficient evidence. CONCLUSION: Skills
      training interventions improved several aspects of emotional health in community
      dwelling older adults, while the effects for other outcomes and interventions
      lacked clear evidence. We discuss the implications and challenges in moving
      forward in this important area.

PMID- 25964925
TI  - Chronic disease self-management support: public health perspectives.

PMID- 25964926
TI  - CDC and YMCA: A Promising Partnership for Delivering Fall Prevention Programing.

PMID- 25964927
TI  - Fostering Healthy Aging through Evidence-Based Prevention Programs: Perspectives
      from the Administration for Community Living/Administration on Aging.

PMID- 25964928
TI  - Factors Supporting Implementation among CDSMP Organizations.
AB  - Reaching individuals who can benefit from evidence-based health promotion and
      disability prevention programs is a goal of federal, state, and local agencies as
      well as researchers, providers, community agencies, and other stakeholders.
      Implementation effectiveness at the organizational level must be achieved in
      order to reach these individuals and sustain the program. This mixed methods
      study examined eight organizations within two states that successfully
      implemented the Chronic Disease Self-Management Program (CDSMP) and sustained it
      from 4 to 10 years. There were two types of organizations: aging services and
      health care. Internal and external implementation factors and influences were
      explored. Additional examination of state activities (as a key external agent
      supporting CDSMP implementation) was conducted. The examination found agreement
      among the eight organizations regarding why they had adopted the CDSMP - citing
      the alignment between the program and their organizations' mission and purpose to
      improve health status and promote better self-care, and the demonstrated value
      (benefits) of the program. Organizations were also alike in that they described
      the importance of an internal champion and supportive senior leader.
      Organizations differed in how they experienced and valued peer support and
      collaborative networks. Organizations also differed in how they filled their
      CDSMP workshops. Internal drivers and capability were more often discussed as
      facilitating successful implementation than external factors. However, state
      activities and external support enabled successful adoption - particularly
      funding and training. The primary challenges identified by this set of
      organizations included difficulty in recruiting participants (filling workshops)
      and irregular or insufficient funding sources. These challenges were identified
      as significant and represented barriers to sustaining the program. 

PMID- 25964929
TI  - Chronic disease self-management program: insights from the eye of the storm.

PMID- 25964930
TI  - Working toward a Multi-Program Strategy in Fall Prevention.

PMID- 25964931
TI  - Improving Lives through Evidence-Based Health Promotion Programs: A National
      Priority.

PMID- 25964932
TI  - Translating PEARLS: Lessons Learned from Providers and Participants.

PMID- 25964933
TI  - Factors Associated with Successful Completion of the Chronic Disease Self
      Management Program among Middle-Aged and Older Asian-American Participants: A
      National Study.
AB  - Asian-Americans are a small but fast-growing population in the United States who
      are increasingly experiencing multiple chronic diseases. While the evidence-based
      Chronic Disease Self-Management Program (CDSMP) has been disseminated among
      various racial and ethnic populations, few studies specifically investigate
      participants with an Asian background. The study aims to identify characteristics
      of middle-aged and older Asian-American CDSMP participants (older than 50 years)
      and investigate factors related to successful workshop completion (i.e.,
      attending 4+ of the 6 sessions) among this population. Data were analyzed from
      2,716 middle-aged and older Asian-Americans collected during a 2-year national
      dissemination of CDSMP. Multilevel logistic regression analyses were conducted to
      identify individual- and workshop-level covariates related to successful workshop
      completion. The majority of participants were female, living with others, and
      living in metro areas. The average age was 71.3 years old (+/-9.2), and the
      average number of chronic conditions was 2.0 (+/-1.5). Successful completion of
      CDSMP workshops among participants was associated with their number of chronic
      conditions (OR = 1.10, P = 0.011), living in non-metro areas (OR = 1.77, P =
      0.009), attending workshops from area agencies on aging (OR = 1.56, P = 0.018),
      and attending a workshop with higher completion rates (OR = 1.03, P < 0.001).
      This study is the first large-scale examination of Asian-American participants
      enrolled in CDSMP and highlights characteristics related to intervention
      attendance among this under-studied minority population. Knowing such
      characteristics is important for serving the growing number of Asian-Americans
      with chronic conditions. 

PMID- 25964934
TI  - Fall prevention in community settings: results from implementing tai chi: moving
      for better balance in three States.
AB  - Tai Chi: Moving for Better Balance (TCMBB) is an evidence-based fall prevention
      exercise program being disseminated in selected communities through state injury
      prevention programs. This study: (1) describes the personal characteristics of
      TCMBB participants; (2) quantifies participants' functional and self-reported
      health status at enrollment; and (3) measures changes in participants' functional
      and self-reported health status post-intervention. There were 421 participants
      enrolled in 36 TCMBB programs delivered in Colorado, New York, and Oregon. Of the
      209 participants who completed both baseline enrollment and post-intervention
      surveys, the average age of participants was 75.3 (SD +/- 8.2) years. Most
      participants were female (81.3%), non-Hispanic (96.1%), White (94.1%), and
      described themselves as in excellent or very good health (52.2%). Paired t-test
      and general estimating equation models assessed changes over the 3-month program
      period. Pre- and post-assessment self-reported surveys and objective functional
      data [Timed Up and Go (TUG) test] were collected. On average, TUG test scores
      decreased (p < 0.001) for all participants; however, the decrease was most
      noticeable among high-risk participants (mean decreased from 18.5 to 15.7 s). The
      adjusted odds ratio of reporting feeling confident that a participant could keep
      themselves from falling was five times greater after completing the program.
      TCMBB, which addresses gait and balance problems, can be an effective way to
      reduce falls among the older adult population. By helping older adults maintain
      their functional abilities, TCMBB can help community-dwelling older adults
      continue to live independently. 

PMID- 25964935
TI  - The CDC Healthy Aging Research Network: Advancing Science toward Action and
      Policy for the Evidence-Based Health Promotion Movement.

PMID- 25964936
TI  - Texercise: the evolution of a health promotion program.

PMID- 25964937
TI  - EnhanceFitness: A 20-Year Dissemination History.

PMID- 25964938
TI  - A matter of balance: older adults taking control of falls by building confidence.

PMID- 25964939
TI  - A missing piece in the infrastructure to promote healthy aging programs:
      education and work force development.

PMID- 25964940
TI  - The conversion of a practice-based lifestyle enhancement program into a
      formalized, testable program: from texercise classic to texercise select.
AB  - Little is known about the structure, content, and benefits of practice-based or
      grass roots health programs that have been widely delivered by a variety of
      community organizations and stakeholders. This perspective will document the
      natural history of Texercise Classic, a state-endorsed but previously untested
      lifestyle health promotion program. It will: (1) discuss Texercise Classic's
      participant reach and adoption over time; (2) describe the rationale and
      processes employed to formalize Texercise Classic into a more structured program
      known as Texercise Select; (3) outline the essential elements and activities
      included in Texercise Select and contrast them with those included in Texercise
      Classic; and (4) highlight key components for uniform facilitator training. The
      discussion will reflect upon the evolution of Texercise, compare and contrast the
      benefits and challenges of each program, and review the "next steps" for
      Texercise Select. In contrasting Texercise Classic and Select, it is important to
      understand the benefits and challenges of both programs. Preliminary results
      indicate that Texercise Select is effective, yet its ability to sustain the same
      reach as Texercise Classic remains unknown and an area for future study. 

PMID- 25964941
TI  - Methods for streamlining intervention fidelity checklists: an example from the
      chronic disease self-management program.
AB  - Maintaining intervention fidelity should be part of any programmatic quality
      assurance (QA) plan and is often a licensure requirement. However, fidelity
      checklists designed by original program developers are often lengthy, which makes
      compliance difficult once programs become widely disseminated in the field. As a
      case example, we used Stanford's original Chronic Disease Self-Management Program
      (CDSMP) fidelity checklist of 157 items to demonstrate heuristic procedures for
      generating shorter fidelity checklists. Using an expert consensus approach, we
      sought feedback from active master trainers registered with the Stanford
      University Patient Education Research Center about which items were most
      essential to, and also feasible for, assessing fidelity. We conducted three
      sequential surveys and one expert group-teleconference call. Three versions of
      the fidelity checklist were created using different statistical and
      methodological criteria. In a final group-teleconference call with seven national
      experts, there was unanimous agreement that all three final versions (e.g., a 34
      item version, a 20-item version, and a 12-item version) should be made available
      because the purpose and resources for administering a checklist might vary from
      one setting to another. This study highlights the methodology used to generate
      shorter versions of a fidelity checklist, which has potential to inform future QA
      efforts for this and other evidence-based programs (EBP) for older adults
      delivered in community settings. With CDSMP and other EBP, it is important to
      differentiate between program fidelity as mandated by program developers for
      licensure, and intervention fidelity tools for providing an "at-a-glance"
      snapshot of the level of compliance to selected program indicators. 

PMID- 25964942
TI  - Healthcare providers' perceptions and self-reported fall prevention practices:
      findings from a large new york health system.
AB  - Among older adults, falls are the leading cause of injury-related deaths and
      emergency department visits, and the incidence of falls in the United States is
      rising as the number of older Americans increases. Research has shown that falls
      can be reduced by modifying fall-risk factors using multifactorial interventions
      implemented in clinical settings. However, the literature indicates that many
      providers feel that they do not know how to conduct fall-risk assessments or do
      not have adequate knowledge about fall prevention. To help healthcare providers
      incorporate older adult fall prevention (i.e., falls risk assessment and
      treatment) into their clinical practice, the Centers for Disease Control and
      Prevention's (CDC) Injury Center has developed the Stopping Elderly Accidents,
      Deaths, and Injuries (STEADI) tool kit. This study was conducted to identify the
      practice characteristics and providers' beliefs, knowledge, and fall-related
      activities before they received training on how to use the STEADI tool kit. Data
      were collected as part of a larger State Fall Prevention Project funded by CDC's
      Injury Center. Completed questionnaires were returned by 38 medical providers
      from 11 healthcare practices within a large New York health system. Healthcare
      providers ranked falls as the lowest priority of five conditions, after diabetes,
      cardiovascular disease, mental health, and musculoskeletal conditions. Less than
      40% of the providers asked most or all of their older patients if they had fallen
      during the past 12 months. Less than a quarter referred their older patients to
      physical therapists for balance or gait training, and <20% referred older
      patients to community-based fall prevention programs. Less than 16% reported they
      conducted standardized functional assessments with their older patients at least
      once a year. These results suggest that implementing the STEADI tool kit in
      clinical settings could address knowledge gaps and provide the necessary tools to
      help providers incorporate fall-risk assessment and treatment into clinical
      practice. 

PMID- 25964943
TI  - Workshop characteristics related to chronic disease self-management education
      program attendance.
AB  - Using the national dissemination of Chronic Disease Self-Management Education
      (CDSME) programs, the purposes of this study were to (1) document intervention
      attendance rates as related to the number of participants enrolled in the
      workshop and (2) compare the relationship between workshop attendance and
      workshop size by delivery site rurality and type. Data were analyzed from the
      first 100,000 middle-aged and older adults who participated in CDSME workshops
      spanning 45 states, Puerto Rico, and the District of Columbia as part of the
      American Recovery and Reinvestment Act of 2009 Communities Putting Prevention to
      Work: Chronic Disease Self-Management Program initiative. Descriptive statistics
      are reported for all participants, then separately by each delivery site type.
      Ratios between the number of workshop participants and the number of workshop
      sessions attended were calculated and graphed based on the rurality of delivery
      and separately for the leading five delivery site types. Associations between the
      number of workshop participants and the number of sessions attended differed by
      delivery site rurality and type. Findings have implications for participant
      retention and workshop delivery costs, which can assist program deliverers to
      strategically plan implementation efforts in their areas. 

PMID- 25964944
TI  - Gait Speed among Older Participants Enrolled in an Evidence-Based Fall Risk
      Reduction Program: A Subgroup Analysis.
AB  - BACKGROUND: Functional decline is a primary risk factor for institutionalization
      and mortality among older adults. Although community-based fall risk reduction
      programs have been widely disseminated, little is known about their impact on
      gait speed, a key indicator of functional performance. Changes in functional
      performance between baseline and post-intervention were examined by means of
      timed up and go (TUG), a standardized functional assessment test administered to
      participants enrolled in A Matter of Balance/Volunteer Lay Leader (AMOB/VLL)
      model, an evidence-based fall risk reduction program. METHODS: This study
      included 71 participants enrolled in an AMOB/VLL program in the Brazos Valley and
      South Plain regions of Texas. Paired t-tests were employed to assess program
      effects on gait speed at baseline and post-intervention for all participants and
      by subgroups of age, sex, living status, delivery sites, and self-rated health.
      The Bonferroni correction was applied to adjust inflated Type I error rate
      associated with performing multiple t-tests, for which p-values <0.0042 (i.e.,
      0.5/12 comparisons) were deemed statistically significant. RESULTS: Overall, gait
      speed of enrolled participants improved from baseline to post-intervention (t =
      3.22, p = 0.002). Significant changes in TUG scores were observed among
      participants who lived with others (t = 4.45, p < 0.001), rated their health as
      excellent, very good, or good (t = 3.05, p = 0.003), and attended program
      workshops at senior centers (t = 3.52, p = 0.003). CONCLUSION: Findings suggest
      community-based fall risk reduction programs can improve gait speed for older
      adults. More translational research is needed to understand factors related to
      the effectiveness of fall risk reduction programs in various populations and
      settings.

PMID- 25964945
TI  - Cost-effectiveness of the chronic disease self-management program: implications
      for community-based organizations.
AB  - Chronic conditions are the leading cause of growing healthcare spending,
      disability, and death in the U.S. In the wake of national health reform, policy
      makers and healthcare professionals are becoming increasingly concerned in
      containing healthcare costs while improving quality of patient care. A basic
      policy question is whether the Chronic Disease Self-Management Program (CDSMP), a
      widely distributed evidenced-based self-managed program, can be cost-effective in
      managing chronic conditions while improving quality of life. Utilizing data from
      the National Study of CDSMP, the primary objective of the current study is to
      estimate cost-effectiveness of the CDSMP program among individuals with at least
      one chronic condition. The second objective is to determine how cost
      effectiveness ratios vary by depression status. EuroQol-5D (EQ-5D) was used to
      measure health-related quality of life (HRQOL) of CDSMP participants, which was
      then converted to quality-adjusted life years (QALYs) for cost-effectiveness
      analysis. Participants who completed the CDSMP program experienced higher EQ-5D
      scores from baseline to 12-month follow-up (increased from 0.736 to 0.755; p <
      0.001). The incremental cost-effectiveness ratio (ICER) ranges from $83,285 to
      $31,285 per QALYs, which can be comparable to the common benchmark of
      $50,000/QALYs. ICER by baseline depression status indicates that it will cost
      more per QALYs gained for those diagnosed with depression based on their Patient
      Health Questionnaire-8 score. However, cautions should be taken while considering
      this point estimate too literally because the average cost for CDSMP participants
      was a rough estimate and based on several simplifying assumptions. Identifying
      cost-effective strategies that can lower the burden of chronic disease among
      community-dwelling adults is critical for decision makers in allocating limited
      resources. Policy makers and community organizations can use this information to
      guide funding decisions and delivery of CDSMP programs for individuals with
      multiple chronic health conditions. 

PMID- 25964946
TI  - Healthcare cost savings estimator tool for chronic disease self-management
      program: a new tool for program administrators and decision makers.
AB  - Chronic disease self-management education (CDSME) programs have been delivered to
      more than 100,000 older Americans with chronic conditions. As one of the Stanford
      suite of evidence-based CDSME programs, the chronic disease self-management
      program (CDSMP) has been disseminated in diverse populations and settings. The
      objective of this paper is to introduce a practical, universally applicable tool
      to assist program administrators and decision makers plan implementation efforts
      and make the case for continued program delivery. This tool was developed
      utilizing data from a recent National Study of CDSMP to estimate national savings
      associated with program participation. Potential annual healthcare savings per
      CDSMP participant were calculated based on averted emergency room visits and
      hospitalizations. While national data can be utilized to estimate cost savings,
      the tool has built-in features allowing users to tailor calculations based on
      their site-specific data. Building upon the National Study of CDSMP's documented
      potential savings of $3.3 billion in healthcare costs by reaching 5% of adults
      with one or more chronic conditions, two heuristic case examples were also
      explored based on different population projections. The case examples show how a
      small county and large metropolitan city were not only able to estimate
      healthcare savings ($38,803 for the small county; $732,290 for the large
      metropolitan city) for their existing participant populations but also to project
      significant healthcare savings if they plan to reach higher proportions of middle
      aged and older adults. Having a tool to demonstrate the monetary value of CDSMP
      can contribute to the ongoing dissemination and sustainability of such community
      based interventions. Next steps will be creating a user-friendly, internet-based
      version of Healthcare Cost Savings Estimator Tool: CDSMP, followed by broadening
      the tool to consider cost savings for other evidence-based programs. 

PMID- 25964947
TI  - Characterization of rubella seronegative females in the zambian blood donor
      community.
AB  - Rubella is an acute, contagious viral infection caused by a teratogenic enveloped
      single-stranded RNA virus, rubella virus, a member of the togaviridae family.
      Though causing generally mild infections in children and adults, it is a disease
      of public health importance in pregnant women causing major problems including
      abortions, miscarriages, and congenital rubella syndrome in more than 20% of the
      susceptible population. This study was carried out to determine the
      characteristics associated with rubella seronegativity among female blood donors
      in Zambia. Rubella-specific IgG antibody levels were measured in the blood serum.
      Proportions were compared using the Chi-squared test at the 5% significance
      level, and magnitudes of associations were determined using the odds ratio and
      its 95% confidence interval. Of the 124 female blood donors tested for rubella
      IgG 46.0% were aged <20 years. Overall, 66.7% of the participants had never been
      married. More than half (62.1%) of the participants resided in rural areas of the
      country. Of the 114 participants with recorded level of education, 50.1% had at
      least completed secondary school. Out of 43 participants with recorded current
      employment status, 44.2% were not working for pay. A total of 10 (8.1%)
      participants were seronegative to rubella IgG antibodies. No factors were
      associated with seronegativity. Protection against rubella through natural
      infection appears inadequate to protect the population, increasing the risk of
      CRS. 

PMID- 25964948
TI  - A history of undergraduate education for public health: from behind the scenes to
      center stage.

PMID- 25964949
TI  - Reaching diverse participants utilizing a diverse delivery infrastructure: a
      replication study.
AB  - This replication study examines participant recruitment and program adoption
      aspects of disease self-management programs by delivery site types. Data were
      analyzed from 58,526 adults collected during a national dissemination of the
      Stanford suite of chronic disease self-management education programs spanning 45
      states, the District of Columbia, and Puerto Rico. Participant data were analyzed
      using multinomial logistic regression to generate profiles by delivery site type.
      Profiles were created for the five leading delivery site types, which included
      senior centers or area agencies on aging, residential facilities, healthcare
      organizations, community or multi-purpose centers, and faith-based organizations.
      Significant variation in neighborhood characteristics (e.g., rurality, median
      household income, percent of the population age 65 years and older, percent of
      the population i.e., non-Hispanic white) and participant characteristics (e.g.,
      age, sex, ethnicity, race, rurality) were observed by delivery site type. Study
      findings confirm that these evidence-based programs are capable of reaching large
      numbers of diverse participants through the aging services network. Given the
      importance of participant reach and program adoption to the success of
      translational research dissemination initiatives, these findings can assist
      program deliverers to create strategic plans to engage community partners to
      diversify their participant base. 

PMID- 25964950
TI  - Lauric Acid Production in a Glycogen-Less Strain of Synechococcus sp. PCC 7002.
AB  - The cyanobacterium Synechococcus sp. Pasteur culture collection 7002 was
      genetically engineered to synthesize biofuel-compatible medium-chain fatty acids
      (FAs) during photoautotrophic growth. Expression of a heterologous lauroyl-acyl
      carrier protein (C12:0-ACP) thioesterase with concurrent deletion of the
      endogenous putative acyl-ACP synthetase led to secretion of transesterifiable
      C12:0 FA in CO2-supplemented batch cultures. When grown at steady state over a
      range of light intensities in a light-emitting diode turbidostat photobioreactor,
      the C12-secreting mutant exhibited a modest reduction in growth rate and
      increased O2 evolution relative to the wild-type (WT). Inhibition of (i) glycogen
      synthesis by deletion of the glgC-encoded ADP-glucose pyrophosphorylase (AGPase)
      and (ii) protein synthesis by nitrogen deprivation were investigated as potential
      mechanisms for metabolite redistribution to increase FA synthesis. Deletion of
      AGPase led to a 10-fold decrease in reducing carbohydrates and secretion of
      organic acids during nitrogen deprivation consistent with an energy spilling
      phenotype. When the carbohydrate-deficient background (DeltaglgC) was modified
      for C12 secretion, no increase in C12 was achieved during nutrient replete
      growth, and no C12 was recovered from any strain upon nitrogen deprivation under
      the conditions used. At steady state, the growth rate of the DeltaglgC strain
      saturated at a lower light intensity than the WT, but O2 evolution was not
      compromised and became increasingly decoupled from growth rate with rising
      irradiance. Photophysiological properties of the DeltaglgC strain suggest energy
      dissipation from photosystem II and reconfiguration of electron flow at the level
      of the plastoquinone pool. 

PMID- 25964952
TI  - Peptide Sequence Region That is Essential for the Interactions of the
      Enterotoxigenic Bacteroides fragilis Metalloproteinase II with E-cadherin.
AB  - Bacteroides fragilis is a valuable anaerobic commensal and an essential component
      of the gut microbiome in humans. The presence of a short pathogenicity island in
      the genome is predominantly associated with the enterotoxigenic strains of B.
      fragilis. Metallopro-teinase II (MPII) and fragilysin (FRA) are the structurally
      related enzymes encoded by the pathogenicity island in the enterotoxigenic
      strains. Accordingly, there is a significant overlap between the cleavage
      preferences of MPII and FRA. These proteinases, however, are counter-transcribed
      in the bacterial genome suggesting their distinct and specialized functions in
      the course of infection. It is well established that FRA directly cleaves E
      cadherin, a key protein of the cell-to-cell adhesion junctions in the intestinal
      epithelium. Counterintuitively, MPII directly binds to, rather than cleaves, E
      cadherin. Structural modeling suggested that a potential E-cadherin binding site
      involves the C-terminal -helical region of the MPII catalytic domain. The
      sequence of this region is different in MPII and FRA. Here, we employed
      substitution mutagenesis of this C-terminal -helical region to isolate the MPII
      mutants with the potentially inactivated E-cadherin binding site. Overall, as a
      result of our modeling, mutagenesis and binding studies, we determined that the C
      terminal ten residue segment is essential for the binding of MPII, but not of
      FRA3, to E-cadherin, and that the resulting MPII*E-cadherin complex does not
      impair E-cadherin-dependent cell-to-cell contacts. It is possible to envision
      that the putative cleavage targets of MPII should be explored not only on the
      host cell surface but also in B. fragilis.

PMID- 25964953
TI  - Erratum: Nasopharyngeal carcinoma in Brunei Darussalam: low incidence among the
      Chinese and an evaluation of antibodies to Epstein-Barr virus antigens as
      biomarkers.
AB  - [This corrects the article on p. 371 in vol. 50, PMID: 19421680.]. 

PMID- 25964951
TI  - Risk factors for trauma-induced coagulopathy- and transfusion-associated multiple
      organ failure in severely injured trauma patients.
AB  - BACKGROUND: Both trauma-induced coagulopathy (TIC) and transfusion strategies
      influence early outcome in hemorrhagic trauma patients. Their impact on late
      outcome is less well characterized. This study systematically reviews risk
      factors for TIC- and transfusion-associated multiple organ failure (MOF) in
      severely injured trauma patients. MATERIALS AND METHODS: A systematic search was
      conducted in PubMed and Embase. Studies published from 1986 to 2013 on adult
      trauma patients with an injury severity score >=16, investigating TIC or
      transfusion strategies with MOF as primary or secondary outcome, were eligible
      for inclusion. Results of the included studies were evaluated with meta-analyses
      of pooled data. RESULTS: In total, 50 studies were included with a total sample
      size of 63,586 patients. Due to heterogeneity of the study populations and
      outcome measures, results from 7 studies allowed for pooling of data. Risk
      factors for TIC-associated MOF were hypocoagulopathy, hemorrhagic shock,
      activated protein C, increased histone levels, and increased levels of markers of
      fibrinolysis on admission. After at least 24 h after admission, the occurrence of
      thromboembolic events was associated with MOF. Risk factors for transfusion
      associated MOF were the administration of fluids and red blood cell units within
      24 h post-injury, the age of red blood cells (>14 days) and a ratio of FFP:RBC >=
      1:1 (OR 1.11, 95% CI 1.04-1.19). CONCLUSION: Risk factors for TIC-associated MOF
      in severely injured trauma patients are early hypocoagulopathy and hemorrhagic
      shock, while a hypercoagulable state with the occurrence of thromboembolic events
      later in the course of trauma predisposes to MOF. Risk factors for transfusion
      associated MOF include administration of crystalloids and red blood cells and a
      prolonged storage time of red blood cells. Future prospective studies
      investigating TIC- and transfusion-associated risk factors on late outcome are
      required.

PMID- 25964954
TI  - Reply to Sabatelli et al.: Detecting collagen VI in Bethlem myopathy.

PMID- 25964955
TI  - Reply to Kelder et al.: Does the dorsal mesenchymal protrusion act as a temporary
      pacemaker during heart development?

PMID- 25964956
TI  - Development and utilization of a web-based application as a robust radiology
      teaching tool (radstax) for medical student anatomy teaching.
AB  - Rationale and Objectives: The primary role of radiology in the preclinical
      setting is the use of imaging to improve students' understanding of anatomy. Many
      currently available Web-based anatomy programs include either suboptimal or
      overwhelming levels of detail for medical students.Our objective was to develop a
      user-friendly software program that anatomy instructors can completely tailor to
      match the desired level of detail for their curriculum, meets the unique needs of
      the first- and the second-year medical students, and is compatible with most
      Internet browsers and tablets.Materials and Methods: RadStax is a Web-based
      application developed using free, open-source, ubiquitous software. RadStax was
      first introduced as an interactive resource for independent study and later
      incorporated into lectures. First- and second-year medical students were surveyed
      for quantitative feedback regarding their experience.Results: RadStax was
      successfully introduced into our medical school curriculum. It allows the
      creation of learning modules with labeled multiplanar (MPR) image sets, basic
      anatomic information, and a self-assessment feature. The program received
      overwhelmingly positive feedback from students. Of 115 students surveyed, 87.0%
      found it highly effective as a study tool and 85.2% reported high user
      satisfaction with the program.Conclusions: RadStax is a novel application for
      instructors wishing to create an atlas of labeled MPR radiologic studies tailored
      to meet the specific needs their curriculum. Simple and focused, it provides an
      interactive experience for students similar to the practice of radiologists.This
      program is a robust anatomy teaching tool that effectively aids in educating the
      preclinical medical student.

PMID- 25964957
TI  - Food and feed safety assessment: the importance of proper sampling.
AB  - The general principles for safety and nutritional evaluation of foods and feed
      and the potential health risks associated with hazardous compounds are described
      as developed by the Food and Agriculture Organization (FAO) and the World Health
      Organization (WHO) and further elaborated in the European Union-funded project
      Safe Foods. We underline the crucial role of sampling in foods/feed safety
      assessment. High quality sampling should always be applied to ensure the use of
      adequate and representative samples as test materials for hazard identification,
      toxicological and nutritional characterization of identified hazards, as well as
      for estimating quantitative and reliable exposure levels of foods/feed or related
      compounds of concern for humans and animals. The importance of representative
      sampling is emphasized through examples of risk analyses in different areas of
      foods/feed production. The Theory of Sampling (TOS) is recognized as the only
      framework within which to ensure accuracy and precision of all sampling steps
      involved in the field-to-fork continuum, which is crucial to monitor foods and
      feed safety. Therefore, TOS must be integrated in the well-established FAO/WHO
      risk assessment approach in order to guarantee a transparent and correct frame
      for the risk assessment and decision making process.

PMID- 25964958
TI  - Diagnostic value of medical history and physical examination of anterior cruciate
      ligament injury: comparison between primary care physician and orthopaedic
      surgeon.
AB  - PURPOSE: Well-designed validity studies on the clinical diagnosis of anterior
      cruciate ligament (ACL) injury are scarce. Our purpose is to assess the
      diagnostic value of ACL-specific medical history assessment and physical
      examination between primary and secondary care medical specialists. METHODS:
      Medical history assessment and physical examination were performed by both an
      orthopaedic surgeon and a primary care physician, both blinded to all clinical
      information, in a secondary care population. A knee arthroscopy was used as
      reference standard. A total of 60 participants were divided into an index group
      with an arthroscopically proven complete ACL rupture and a control group with an
      arthroscopically proven intact ACL. RESULTS: The orthopaedic surgeon recognized
      94 % of the participants with an ACL rupture through a positive medical history
      combined with a positive physical examination; of the participants with an intact
      ACL, 16 % were misclassified by the orthopaedic surgeon. The primary care
      physician recognized 62 % of the participants with an ACL rupture and
      misclassified 23 % of the participants with an intact ACL. Physical examination
      appeared to have no additional value for the primary care physician. CONCLUSIONS:
      Combined medical history and physical examination have strong diagnostic value in
      ACL rupture diagnostics performed by an orthopaedic surgeon, whereas for the
      primary care physician, only medical history appeared to be of value. For current
      practice, this could mean that only orthopaedic surgeons can perform an ACL
      physical examination with accuracy. LEVEL OF EVIDENCE: III.

PMID- 25964959
TI  - NFkappaB pathway and microRNA-9 and -21 are involved in sensitivity to the
      pterocarpanquinone LQB-118 in different CML cell lines.
AB  - Chronic myeloid leukemia (CML), a myeloproliferative disorder characterized by
      the BCR-ABL oncoprotein, presents its treatment based on tyrosine kinase
      inhibitors (TKIs), mainly imatinib. However, despite its clinical success, almost
      30% of all CML patients demand alternative therapy. In this context, the
      development of drugs capable of overcoming TKIs resistance is imperative. The
      pterocarpanquinone-LQB-118 is a novel compound with anti-tumor effect in CML
      cells whose mechanism of action is being elucidated. Here, we demonstrate that in
      two CML cell lines exhibiting different biological characteristics, LQB-118
      modulates NFkappaB subcellular localization, apparently independently of the AKT
      and MAPK pathways, partially inhibits proteasome activity, and alters the
      expression of microRNAs -9 and -21.

PMID- 25964960
TI  - Response.

PMID- 25964961
TI  - Solving a treatment dilemma.

PMID- 25964962
TI  - Rivaroxaban 2.5 mg. No justification for using this anticoagulant after an acute
      coronary syndrome.
AB  - Aspirin is the antithrombotic drug of choice for preventing recurrences after a
      first acute coronary syndrome. The addition of clopidogrel, another antiplatelet
      agent, is helpful in case of angioplasty with stenting. Following the acute
      phase, warfarin, an anticoagulant, alone or in combination with aspirin, may be
      used only in specific situations, particularly for patients with a high
      thrombotic risk (due to atrial fibrillation for example). Rivaroxaban, an oral
      factor Xa inhibitor anticoagulant, has been authorised for use following an acute
      coronary syndrome, but at a new dose strength of 2.5 mg, in combination with
      aspirin alone or aspirin plus clopidogrel. Rivaroxaban has not been compared with
      warfarin in patients with a high thrombotic risk following an acute coronary
      syndrome. In a double-blind, randomised, placebo-controlled trial in 15 526
      patients, who were not at particularly high risk of thrombosis, the addition of
      the rivaroxaban to aspirin or to aspirin plus clopidogrel appeared to reduce
      mortality during the first year of treatment (2.6% versus 3.8% with placebo).
      However, there is a large amount of missing data, exceeding the inter-group
      difference in the number of deaths, seriously undermining the results. In the
      subgroup of about 1000 patients in whom antiplatelet therapy consisted of aspirin
      alone, addition of rivaroxaban did not lead to a statistically significant
      decrease in the incidence of cardiovascular events or death. The addition of
      rivaroxaban increased the incidence of "clinically relevant" bleeding episodes,
      as defined in the study protocol (11.2% of patients per year in the rivaroxaban
      group versus 6.4% in the placebo group), as well as the incidence of major
      bleeding events (respectively 1.2% and 0.3% of patients per year) and
      intracranial haemorrhage (14 versus 5 cases). The patients selected for this
      trial were considered to have a low risk of bleeding, so the risk is likely to be
      higher in many patients who have had an acute coronary syndrome. In practice, it
      has not yet been demonstrated that adding rivaroxaban to aspirin or to aspirin
      plus clopidogrel is beneficial following an acute coronary syndrome. In addition,
      the bleeding risk is likely to be higher in routine practice than in the
      conditions under which the comparative trial was conducted. It is therefore best
      not to use rivaroxaban in this setting but to stick with best-known
      antithrombotic drugs.

PMID- 25964963
TI  - Antithrombotic treatment after an acute coronary syndrome.

PMID- 25964964
TI  - Bedaquiline. More data needed on this dangerous antitubercular drug.
AB  - Active tuberculosis is a serious, sometimes fatal, bacterial infection. Multidrug
      resistant strains are associated with higher mortality. Bedaquiline, a
      diarylquinoline antibiotic, has been authorised in the EU, in combination with
      other antibiotics, for patients with multidrug-resistant pulmonary tuberculosis.
      Clinical evaluation of bedaquiline in multidrug-resistant tuberculosis is based
      on a double-blind, randomised, placebo-controlled trial including 160 patients.
      During follow-up, there were 10 deaths in the bedaquiline group (including 5
      deaths from disease progression) and 2 deaths (both due to tuberculosis) in the
      placebo group. An analysis of data on 133 patients showed that it took a median
      of 83 days for sputum cultures to become negative in the bedaquiline group,
      versus 125 days in the placebo group (p = 0.0004). QT prolongation and hepatic
      and pancreatic disorders were more frequent with bedaquiline than with placebo.
      The most frequently reported adverse effects were headache, nausea, arthralgia
      and pulmonary infections. In practice, bedaquiline reduced the number of
      contagious patients with multidrug-resistant pulmonary tuberculosis, but
      mortality was higher than in the placebo group. Its harm-benefit balance is
      unclear, especially in patients with extensively drug-resistant tuberculosis, for
      whom there are very few active antibiotics available.

PMID- 25964966
TI  - Clevidipine. Hypertensive crises during surgery: no advance.
AB  - Beware of hypersensitivity reactions to the lipid emulsion.

PMID- 25964965
TI  - Iixisenatide. Wait for conclusive results on complications of diabetes.
AB  - There is no firm evidence that lixisenatide prevents the clinical complications
      of diabetes. Given the many potentially serious adverse effects of incretin
      analogues of this type, the lack of benefit skews the balance towards greater
      harm.

PMID- 25964967
TI  - Common stem--lutamide.

PMID- 25964968
TI  - Antibiotics during childhood and inflammatory bowel disease?
AB  - Four epidemiological studies, including two large cohort studies in children aged
      17 years or under, have studied the link between antibiotic therapy and
      inflammatory bowel disease. The risk of inflammatory bowel disease appeared to be
      twice as high in children exposed to an antibiotic as in unexposed children. The
      risk appeared higher following exposure during the first year of life, with beta
      lactam antibiotics, and with repeated antibiotic courses. One postulated
      mechanism is through destruction of the anaerobic intestinal flora by
      antibiotics. In practice, these data provide yet another reason to avoid
      unnecessarily exposing children to antibiotics.

PMID- 25964969
TI  - Transdermal rotigotine in restless legs syndrome: impulse control disorders.
AB  - Detailed case reports have confirmed that the dopamine agonist rotigotine,
      marketed in transdermal patches, exposes patients to the risk of impulse control
      disorders, even at the doses recommended for restless legs syndrome. In most
      cases, the symptoms regressed after reducing the dose or discontinuing the drug.

PMID- 25964970
TI  - Triptans: beware of vasoconstrictive effects.
AB  - Ischaemic disorders, ruptured aneurysm, aortic dissection, gastrointestinal or
      spinal necrosis. And placental infarction in exposed pregnant women.

PMID- 25964971
TI  - Testosterone: myocardial infarction and stroke.
AB  - Testosterone replacement therapy for male hypogonadism can provoke fatal
      cardiovascular events.

PMID- 25964972
TI  - High-dose baclofen: withdrawal syndrome following abrupt discontinuation.

PMID- 25964973
TI  - Abiraterone: thrombocytopenia.

PMID- 25964974
TI  - Migraine and pregnancy. Choice of treatment.

PMID- 25964975
TI  - Triptans during pregnancy.

PMID- 25964976
TI  - Multidrug-resistant tuberculosis: treatment is empirical, for want of robust
      trials.
AB  - Tuberculosis is said to be multi-drug-resistant (MDR-TB) when the mycobacterial
      strain is resistant to both isoniazid and rifampicin in vitro, and "extensively
      multidrug-resistant" (XDR-TB) when the strain is also resistant to
      fluoroquinolones and to at least one aminoglycoside or capreomycin. Multidrug
      resistance greatly increases the lethality of tuberculosis. Patients with
      multidrug-resistant tuberculosis are usually treated for at least 20 months with
      a combination of five antibiotics. For want of better alternatives, extensively
      resistant disease is often treated with antibiotics that have both uncertain
      efficacy and major adverse effects. Antitubercular drug combinations have
      multiple adverse affects and many drug interactions. In practice, the choice of
      drugs is usually empirical, being based on bacteriological criteria and using
      antibiotics with uncertain efficacy but documented harms.

PMID- 25964977
TI  - COPD exacerbations: 5 days of corticosteroid therapy.
AB  - In patients with exacerbations of chronic obstructive pulmonary disease (COPD)
      requiring hospitalisation, 5 days of corticosteroid therapy appears to be as
      effective as 14 days of corticosteroid therapy for preventing recurrences.

PMID- 25964978
TI  - Modest impact of brief interventions on excessive alcohol consumption.
AB  - A meta-analysis suggests that brief behavioural interventions can help some
      drinkers reduce their declared alcohol consumption.

PMID- 25964979
TI  - Obstacles to the universal application of INNs.
AB  - Anomalies in the international non-proprietary name (INN) nomenclature show that
      the international harmonisation of nonproprietary drug names has not been
      achieved. When pharmaceutical companies request a new INN, they try to obtain an
      INN that serves their interests, and then use it for promotional or
      anticompetitive purposes. Drug regulatory agencies are not fulfilling their duty
      to protect existing INNs, particularly with regard to biosimilars (copies of
      biotechnology-derived drugs), giving rise in particular to anomalous names. The
      independence of the World Health Organization INN programme must be safeguarded
      to ensure that the universal terminology it is responsible for developing is
      applied worldwide.

PMID- 25964980
TI  - Premarketing trials: too few patients.

PMID- 25964981
TI  - Interaction Site between the Protein Aggregates and Thiocyanate Ion in Aqueous
      Solution: A Case Study of 1-Butyl-3-methylimidazolium Thiocyanate.
AB  - To investigate the interaction site between amyloid-like protein aggregates and
      thiocyanate (SCN(-)) ion, we studied the relationship between protein aggregation
      (cytochrome c, myoglobin, lysozyme, ribonuclease A, and beta-lactoglobulin) and
      SCN(-) ion in aqueous 1-butyl-3-methylimidazolium thiocyanate ([bmim][SCN])
      solutions using optical spectroscopy. The addition of [bmim][SCN] (>10 mol % IL)
      to a protein solution induced protein aggregation owing to the intermolecular
      beta-sheet structures except in the case of cytochrome c. Analysis of the content
      of 20 amino acid residues for each protein revealed that the degree of
      intermolecular beta-sheet structures (beta%) and midpoint concentration from the
      unfolding to aggregation state ([IL]1/2(U ->betaA)) is correlated primarily with
      the content of Lys residue in proteins (correlation coefficient (R(2)) = 0.97).
      The attractive interaction between the SCN(-) ions and NH3(+) groups of the side
      chain terminal of Lys residue inhibits protein aggregation owing to the
      intermolecular beta-sheet structure. This finding might be related to the
      mechanism for the solubilization of amyloid aggregates by strong denaturants
      containing SCN(-) ions such as guanidine thiocyanate.

PMID- 25964982
TI  - Profilin 2 promotes migration, invasion, and stemness of HT29 human colorectal
      cancer stem cells.
AB  - We investigated the role of profilin 2 in the stemness, migration, and invasion
      of HT29 cancer stem cells (CSCs). Increased and decreased levels of profilin 2
      significantly enhanced and suppressed the self-renewal, migration, and invasion
      ability of HT29 CSCs, respectively. Moreover, profilin 2 directly regulated the
      expression of stemness markers (CD133, SOX2, and beta-catenin) and epithelial
      mesenchymal transition (EMT) markers (E-cadherin and snail). CD133 and beta
      catenin were up-regulated by overexpression of profilin 2 and down-regulated by
      depletion of profilin 2. SOX2 was decreased by profilin 2 depletion. E-cadherin
      was not influenced by profilin 2- overexpression but increased by profilin 2-
      knockdown. The expression of snail was suppressed by profilin 2- knockdown. We
      speculated that stemness and the EMT are closely linked through profilin 2
      related pathways. Therefore, this study indicates that profilin 2 affects the
      metastatic potential and stemness of colorectal CSCs by regulating EMT- and
      stemness-related proteins.

PMID- 25964983
TI  - Structure and Chemistry of SeFx(CN)4-x Compounds.
AB  - Several new SeF2(CN)2-donor complexes with N or O based donor molecules are
      reported. Due to orbital overlap effects 12-crown-4 (1,4,7,10
      tetraoxacyclododecane) shows unsymmetric ether oxygen coordination. Solvent
      coordination (secondary bonding interactions, SBI) in SeFx(CN)4-x compounds is
      weak and does not influence decomposition pathways (neutral and anionic).
      Barriers for decomposition are relatively high in SeF2(CN)2 but decrease
      significantly in compounds with higher cyanide content. In the presence of
      fluoride ions, facile substitution pathways exist; however, reductive elimination
      is also favored. In the absence of fluoride ions decomposition barriers are
      higher, but so are substitution barriers (sigma-metathesis). Therefore,
      successful isolation of Se(CN)4 appears to be significantly hampered. In
      addition, previously unknown trifluoromethyliminoseleniumdifluoride was cleanly
      synthesized utilizing the instability of SeF(CN)3 toward reductive FCN
      elimination (preferred over the thermodynamically favored NCCN elimination) and
      subsequent FCN incorporation to SeF4 through double F-migration. 

PMID- 25964984
TI  - Telomerase activity and cellular aging might be positively modified by a yoga
      based lifestyle intervention.
AB  - OBJECTIVES: Recent studies showed that a brief yoga-based lifestyle intervention
      was efficacious in reducing levels of oxidative stress and cellular aging in
      obese men. The objective of this case report was to assess the efficacy of this
      intervention in reducing the levels of biochemical markers of cellular ageing,
      oxidative stress, and inflammation at baseline (day 0), at the end of active
      intervention (day 10), and follow-up at day 90. DESIGN: Single case report from a
      prospective ongoing study with pre-post design assessing the level of various
      markers of cellular aging. SETTING: Integral Health Clinic, an outpatient
      facility conducting meditation and yoga-based lifestyle intervention programs for
      management of chronic diseases. PATIENT: A 31-year-old man with class I obesity
      (body-mass index, 29.5 kg/m(2)) who presented to the medicine outpatient
      department at All India Institute of Medical Sciences, New Delhi, India, with a
      history of fatigue, difficulty losing weight, and lack of motivation. He noted a
      marked decrease in his energy level, particularly in the afternoon. INTERVENTION:
      A pretested intervention program included asanas (postures), pranayama (breathing
      exercises), stress management, group discussions, lectures, and individualized
      advice. RESULTS: From baseline (day 0) to day 90, the activity of telomerase and
      levels of beta-endorphins, plasma cortisol, and interleukin-6 increased, and a
      sustained reduction in oxidative stress markers, such as reactive oxygen species
      and 8-hydroxy-2-deoxy-guanosine levels. CONCLUSIONS: Adopting yoga/meditation
      based lifestyle modification causes reversal of markers of aging, mainly
      oxidative stress, telomerase activity, and oxidative DNA damage. This may not
      only delay aging and prolong a youthful healthy life but also delay or prevent
      onset of several lifestyle-related diseases, of which oxidative stress and
      inflammation are the chief cause. This report suggests this simple lifestyle
      intervention may be therapeutic for oxidative DNA damage and oxidative stress.

PMID- 25964985
TI  - Contributions of facial expressions and body language to the rapid perception of
      dynamic emotions.
AB  - Correctly perceiving emotions in others is a crucial part of social interactions.
      We constructed a set of dynamic stimuli to determine the relative contributions
      of the face and body to the accurate perception of basic emotions. We also
      manipulated the length of these dynamic stimuli in order to explore how much
      information is needed to identify emotions. The findings suggest that even a
      short exposure time of 250 milliseconds provided enough information to correctly
      identify an emotion above the chance level. Furthermore, we found that
      recognition patterns from the face alone and the body alone differed as a
      function of emotion. These findings highlight the role of the body in emotion
      perception and suggest an advantage for angry bodies, which, in contrast to all
      other emotions, were comparable to the recognition rates from the face and may be
      advantageous for perceiving imminent threat from a distance. 

PMID- 25964986
TI  - Implementing guidelines on reporting research using animals (ARRIVE etc.): new
      requirements for publication in BJP.
AB  - The ARRIVE guidelines have been implemented in BJP for 4 years with the aim of
      increasing transparency in reporting experiments involving animals. BJP has
      assessed our success in implementing them and concluded that we could do better.
      This editorial discusses the issues and explains how we are changing our
      requirements for authors to report their findings in experiments involving
      animals. This is one of a series of editorials discussing updates to the BJP
      Instructions to Authors.

PMID- 25964987
TI  - Visible-light-promoted and one-pot synthesis of phenanthridines and quinolines
      from aldehydes and O-acyl hydroxylamine.
AB  - A one-pot synthesis of phenanthridines and quinolines from commercially available
      or easily prepared aldehydes has been reported. O-(4-Cyanobenzoyl)hydroxylamine
      was utilized as the nitrogen source to generate O-acyl oximes in situ with
      aldehydes catalyzed by Bronsted acid. O-Acyl oximes were then subjected to
      visible light photoredox catalyzed cyclization via iminyl radicals to furnish aza
      arenes. A variety of phenanthridines and quinolines have been prepared assisted
      by Bronsted acid and photocatalyst under visible light at room temperature with
      satisfactory yields. 

PMID- 25964988
TI  - Strong Inhibition of O-Atom Transfer Reactivity for Mn(IV)(O)(pi-Radical
      Cation)(Lewis Acid) versus Mn(V)(O) Porphyrinoid Complexes.
AB  - The oxygen atom transfer (OAT) reactivity of two valence tautomers of a Mn(V)(O)
      porphyrinoid complex was compared. The OAT kinetics of Mn(V)(O)(TBP8Cz) (TBP8Cz =
      octakis(p-tert-butylphenyl)corrolazinato(3-)) reacting with a series of
      triarylphosphine (PAr3) substrates were monitored by stopped-flow UV-vis
      spectroscopy, and revealed second-order rate constants ranging from 16(1) to
      1.43(6) * 10(4) M(-1) s(-1). Characterization of the OAT transition state
      analogues Mn(III)(OPPh3)(TBP8Cz) and Mn(III)(OP(o-tolyl)3)(TBP8Cz) was carried
      out by single-crystal X-ray diffraction (XRD). A valence tautomer of the closed
      shell Mn(V)(O)(TBP8Cz) can be stabilized by the addition of Lewis and Bronsted
      acids, resulting in the open-shell Mn(IV)(O)(TBP8Cz(*+)):LA (LA = Zn(II),
      B(C6F5)3, H(+)) complexes. These Mn(IV)(O)(pi-radical-cation) derivatives exhibit
      dramatically inhibited rates of OAT with the PAr3 substrates (k = 8.5(2) * 10(-3)
      - 8.7 M(-1) s(-1)), contrasting the previously observed rate increase of H-atom
      transfer (HAT) for Mn(IV)(O)(TBP8Cz(*+)):LA with phenols. A Hammett analysis
      showed that the OAT reactivity for Mn(IV)(O)(TBP8Cz(*+)):LA is influenced by the
      Lewis acid strength. Spectral redox titration of Mn(IV)(O)(TBP8Cz(*+)):Zn(II)
      gives Ered = 0.69 V vs SCE, which is nearly +700 mV above its valence tautomer
      Mn(V)(O)(TBP8Cz) (Ered = -0.05 V). These data suggest that the two-electron
      electrophilicity of the Mn(O) valence tautomers dominate OAT reactivity and do
      not follow the trend in one-electron redox potentials, which appear to dominate
      HAT reactivity. This study provides new fundamental insights regarding the
      relative OAT and HAT reactivity of valence tautomers such as M(V)(O)(porph)
      versus M(IV)(O)(porph(*+)) (M = Mn or Fe) found in heme enzymes. 

PMID- 25964990
TI  - Magnetic Nano-skyrmion Lattice Observed in a Si-Wafer-Based Multilayer System.
AB  - Growth, electronic properties, and magnetic properties of an Fe monolayer (ML) on
      an Ir/YSZ/Si(111) multilayer system have been studied using spin-polarized
      scanning tunneling microscopy. Our experiments reveal a magnetic nano-skyrmion
      lattice, which is fully equivalent to the magnetic ground state that has
      previously been observed for the Fe ML on Ir(111) bulk single crystals. In
      addition, the experiments indicate that the interface-stabilized skyrmion lattice
      is robust against local atomic lattice distortions induced by multilayer
      preparation. 

PMID- 25964991
TI  - Optimizing Wellfield Operation in a Variable Power Price Regime.
AB  - Wellfield management is a multiobjective optimization problem. One important
      objective has been energy efficiency in terms of minimizing the energy footprint
      (EFP) of delivered water (MWh/m(3) ). However, power systems in most countries
      are moving in the direction of deregulated markets and price variability is
      increasing in many markets because of increased penetration of intermittent
      renewable power sources. In this context the relevant management objective
      becomes minimizing the cost of electric energy used for pumping and distribution
      of groundwater from wells rather than minimizing energy use itself. We estimated
      EFP of pumped water as a function of wellfield pumping rate (EFP-Q relationship)
      for a wellfield in Denmark using a coupled well and pipe network model. This EFP
      Q relationship was subsequently used in a Stochastic Dynamic Programming (SDP)
      framework to minimize total cost of operating the combined wellfield-storage
      demand system over the course of a 2-year planning period based on a time series
      of observed price on the Danish power market and a deterministic, time-varying
      hourly water demand. In the SDP setup, hourly pumping rates are the decision
      variables. Constraints include storage capacity and hourly water demand
      fulfilment. The SDP was solved for a baseline situation and for five scenario
      runs representing different EFP-Q relationships and different maximum wellfield
      pumping rates. Savings were quantified as differences in total cost between the
      scenario and a constant-rate pumping benchmark. Minor savings up to 10% were
      found in the baseline scenario, while the scenario with constant EFP and
      unlimited pumping rate resulted in savings up to 40%. Key factors determining
      potential cost savings obtained by flexible wellfield operation under a variable
      power price regime are the shape of the EFP-Q relationship, the maximum feasible
      pumping rate and the capacity of available storage facilities. 

PMID- 25964992
TI  - Response to do ultrasonographic semiquantitative indices predict histological
      changes in NASH irrespective of steatosis extent?

PMID- 25964989
TI  - The Voltage-Gated Proton Channel: A Riddle, Wrapped in a Mystery, inside an
      Enigma.
AB  - The main properties of the voltage-gated proton channel (HV1) are described in
      this review, along with what is known about how the channel protein structure
      accomplishes its functions. Just as protons are unique among ions, proton
      channels are unique among ion channels. Their four transmembrane helices sense
      voltage and the pH gradient and conduct protons exclusively. Selectivity is
      achieved by the unique ability of H3O(+) to protonate an Asp-Arg salt bridge.
      Pathognomonic sensitivity of gating to the pH gradient ensures HV1 channel
      opening only when acid extrusion will result, which is crucial to most of its
      biological functions. An exception occurs in dinoflagellates in which influx of
      H(+) through HV1 triggers the bioluminescent flash. Pharmacological interventions
      that promise to ameliorate cancer, asthma, brain damage in ischemic stroke,
      Alzheimer's disease, autoimmune diseases, and numerous other conditions await
      future progress. 

PMID- 25964993
TI  - MP2, CCSD(T), and Density Functional Theory Study of the 2-Butyl Cation: New
      Insight into the Methyl- and Hydrogen-Bridged Structures.
AB  - Using the MP2, CCSD(T), and DFT (B3LYP) methods, the structures and energies of
      the 2-butyl cation (C4H9(+)) were calculated. Energetically, the C-C
      hyperconjugated structure 1 and hydrogen-bridged structure 2 were found to be
      almost identical at all levels. The (13)C NMR chemical shifts of 1 and 2 were
      computed by the GIAO-CCSD(T) method using different geometries. On the basis of
      calculated relative energies and calculated (13)C NMR chemical shifts, an
      equilibrium involving 1 and 2 (in a 50:50 ratio) seemed likely responsible for
      the experimentally observed (13)C NMR chemical shifts in superacid solutions at 
      80  degrees C. However, on the basis of computed and experimental frequencies the
      hydrogen-bridged structure 2 is most likely responsible for the experimentally
      observed frequencies in the solid state at -125  degrees C. 

PMID- 25964994
TI  - Evolution of the SrTiO3-MoO3 Interface Electronic Structure: An in Situ
      Photoelectron Spectroscopy Study.
AB  - Modifying the surface energetics, particularly the work function of advanced
      materials, is of critical importance for a wide range of surface- and interface
      based devices. In this work, using in situ photoelectron spectroscopy, we
      investigated the evolution of electronic structure at the SrTiO3 surface during
      the growth of ultra-thin MoO3 layers. Because of the large work function
      difference between SrTiO3 and MoO3, the energy band alignment on the SrTiO3
      surface is significantly modified. The charge transfer and dipole formation at
      the SrTiO3-MoO3 interface leads to a large modulation of work function and to
      apparent doping in SrTiO3. The measured evolutions of electronic structure and
      upward band bending suggest that the growth of ultra-thin MoO3 layers is a
      powerful tool with which to modulate the surface energetics of SrTiO3, and this
      surface engineering approach could be generalized to other functional oxides. 

PMID- 25964995
TI  - The Tipper-Strominger Hypothesis and Triggering of Allostery in Penicillin
      Binding Protein 2a of Methicillin-Resistant Staphylococcus aureus (MRSA).
AB  - The transpeptidases involved in the synthesis of the bacterial cell wall (also
      known as penicillin-binding proteins, PBPs) have evolved to bind the acyl-D-Ala-D
      Ala segment of the stem peptide of the nascent peptidoglycan for the
      physiologically important cross-linking of the cell wall. The Tipper-Strominger
      hypothesis stipulates that beta-lactam antibiotics mimic the acyl-D-Ala-D-Ala
      moiety of the stem and, thus, are recognized by the PBPs with bactericidal
      consequences. We document that this mimicry exists also at the allosteric site of
      PBP2a of methicillin-resistant Staphylococcus aureus (MRSA). Interactions of
      different classes of beta-lactam antibiotics, as mimics of the acyl-D-Ala-D-Ala
      moiety at the allosteric site, lead to a conformational change, across a distance
      of 60 A to the active site. We directly visualize this change using an
      environmentally sensitive fluorescent probe affixed to the protein loops that
      frame the active site. This conformational mobility, documented in real time,
      allows antibiotic access to the active site of PBP2a. Furthermore, we document
      that this allosteric trigger enables synergy between two different beta-lactam
      antibiotics, wherein occupancy at the allosteric site by one facilitates
      occupancy by a second at the transpeptidase catalytic site, thus lowering the
      minimal-inhibitory concentration. This synergy has important implications for the
      mitigation of facile emergence of resistance to these antibiotics by MRSA.

PMID- 25964997
TI  - The effect of patch potentials in Casimir force measurements determined by
      heterodyne Kelvin probe force microscopy.
AB  - Measurements of the Casimir force require the elimination of the electrostatic
      force between the surfaces. However, due to electrostatic patch potentials, the
      voltage required to minimize the total force may not be sufficient to completely
      nullify the electrostatic interaction. Thus, these surface potential variations
      cause an additional force, which can obscure the Casimir force signal. In this
      paper, we inspect the spatially varying surface potential of e-beamed, sputtered,
      sputtered and annealed, and template stripped gold surfaces with Heterodyne
      amplitude modulated Kelvin probe force microscopy (HAM-KPFM). It is demonstrated
      that HAM-KPFM improves the spatial resolution of surface potential measurements
      compared to amplitude modulated Kelvin probe force microscopy. We find that patch
      potentials vary depending on sample preparation, and that the calculated pressure
      can be similar to the pressure difference between Casimir force calculations
      employing the plasma and Drude models. 

PMID- 25964996
TI  - Food insufficiency, housing and health-related quality of life: results from the
      Positive Spaces, Healthy Places study.
AB  - Studies of people living with HIV who are homeless or unstably housed show a high
      prevalence of food insufficiency (>50%) and associated poor health outcomes;
      however, most evidence is in the form of cross-sectional studies. To better
      understand this issue, we conducted a longitudinal study to examine the impact of
      food insufficiency and housing instability on overall physical and mental health
      related quality of life (HRQoL) among people living with HIV in Ontario. Six
      hundred and two adults living with HIV were enrolled in the Positive Spaces,
      Healthy Places study and followed from 2006 to 2009. Interviewer-administered
      questionnaires were used, and generalized linear mixed-effects models constructed
      to examine longitudinal associations between food insufficiency, housing
      instability and physical and mental HRQoL. At baseline, 57% of participants were
      classified as food insufficient. After adjusting for potential confounders,
      longitudinal analyses revealed a significant, negative association between food
      insufficiency and physical and mental HRQoL outcomes, respectively [effect size
      (ES) with 95% confidence interval (CI): (ES = -2.1, CI = -3.9,-0.3); (ES = -3.5,
      CI = -6.1,-1.5)]. Furthermore, difficulties meeting housing costs were shown to
      have additional negative impacts on mental HRQoL. Food insufficiency is highly
      prevalent among people living with HIV in Ontario, particularly for those with
      unstable housing. This vulnerable group of individuals is in urgent need of
      changes to current housing programmes, services and policies, as well as careful
      consideration of their unmet nutritional needs. 

PMID- 25964998
TI  - A comparative biomechanical analysis of habitually unshod and shod runners based
      on a foot morphological difference.
AB  - Running is one of the most accessible physical activities and running with and
      without footwear has attracted extensive attention in the past several years. In
      this study 18 habitually male unshod runners and 20 habitually male shod runners
      (all with dominant right feet) participated in a running test. A Vicon motion
      analysis system was used to capture the kinematics of each participant's lower
      limb. The in-shoe plantar pressure measurement system was employed to measure the
      pressure and force exerted on the pressure sensors of the insole. The function of
      a separate hallux in unshod runners is analyzed through the comparison of plantar
      pressure parameters. Owing to the different strike patterns in shod and unshod
      runners, peak dorsiflexion and plantarflexion angle were significantly different.
      Habitually shod runners exhibited a decreased foot strike angle (FSA) under
      unshod conditions; and the vertical average loading rate (VALR) of shod runners
      under unshod conditions was larger than that under shod conditions. This suggests
      that the foot strike pattern is more important than the shod or unshod running
      style and runners need to acquire the technique. It can be concluded that for
      habitually unshod runners the separate hallux takes part of the foot loading and
      reduces loading to the forefoot under shod conditions. The remaining toes of
      rearfoot strike (RFS) runners function similarly under unshod conditions. These
      morphological features of shod and unshod runners should be considered in
      footwear design to improve sport performance and reduce injury. 

PMID- 25964999
TI  - Multiple timescales of body schema reorganization due to plastic surgery.
AB  - Plastic surgery modifies the distribution of mass centers of a person's body
      segments, changing his or her posture. The functional reorganization processes
      that lead subjects to re-integrate these body changes into a new stable body
      (posture) schema is poorly understood but current theories suggest the possible
      contribution of two components: a feedback mechanism that strongly depends on
      sensory input and an internal model that is relatively less dependent on sensory
      input and improves posture control, for example by compensating for delayed
      feedback. To assess the relative contributions of these two mechanisms during the
      functional reorganization of a posture scheme, we have conducted a longitudinal
      postural study in a population of healthy adults who were subject to breast
      plastic surgery to reduce or augment body weight. We measured participants'
      orthostatic posture and ground reaction force immediately after, after 4 months,
      and 1 year after the surgery. To investigate the role of visual sensory
      information in the reorganization process we tested the participants with eyes
      open and closed. Our results indicate that participants find a new dynamical
      equilibrium within a few days. However, posture maintenance remains sub-optimal
      long after the center of masses and the resultant of ground reaction force stop
      changing; in some cases, for more than 4 months. Furthermore, the re-adaptation
      process is faster and more efficient in the eyes-open than in the eyes-closed
      condition. These results suggest that the reorganization involves different
      subsystems (responsible for the biomechanical changes, the re-calibration of
      feedback mechanisms, and the re-adaptation of internal models), which act at
      different timescales.

PMID- 25965000
TI  - Effect of different knee starting angles on intersegmental coordination and
      performance in vertical jumps.
AB  - This study aimed to analyze the effect of different knee starting angles on jump
      performance, kinetic parameters, and intersegmental coupling coordination during
      a squat jump (SJ) and a countermovement jump (CMJ). Twenty male volleyball and
      basketball players volunteered to participate in this study. The CMJ was
      performed with knee flexion at the end of the countermovement phase smaller than
      90 degrees  (CMJ(<90)), greater than 90 degrees  (CMJ(>90)), and in a preferred
      position (CMJ(PREF)), while the SJ was performed from a knee angle of 70 degrees 
      (SJ(70)), 90 degrees  (SJ(90)), 110 degrees  (SJ(110)), and in a preferred
      position (SJ(PREF)). The best jump performance was observed in jumps that started
      from a higher squat depth (CMJ(<90)-SJ(70)) and in the preferred positions (CMJ
      and SJ), while peak power was observed in the SJ(110) and CMJ(>90). Analysis of
      continuous relative phase showed that thigh-trunk coupling was more in-phase in
      the jumps (CMJ and SJ) performed with a higher squat depth, while the leg-thigh
      coupling was more in-phase in the CMJ(>90) and SJ(PREF). Jumping from a position
      with knees more flexed seems to be the best strategy to achieve the best
      performance. Intersegmental coordination and jump performance (CMJ and SJ) were
      affected by different knee starting angles.

PMID- 25965001
TI  - Exposure to second hand smoke at home and work among nonsmokers.
AB  - Exposure to second hand smoke (SHS) is associated with adverse health effects.
      This study was undertaken to assess comparative levels of exposure to SHS at home
      and work among nonsmokers aged ?12 years. Data from National Health Examination
      Survey for 1999-2010 were analyzed to estimate exposure to SHS. Total number of
      subjects included in the study was 24,791. Those who self-reported not having
      used any tobacco products during the last five days were considered nonsmokers
      for the purpose of this study. Serum cotinine levels were used as the outcome
      variable to indicate the level of exposure to SHS. Adjusted serum cotinine levels
      for those with no exposure to SHS, exposure to SHS at work only, exposure to SHS
      at home only, and exposure to SHS at home and work were 0.047 (0.044-0.050)n
      g/mL, 0.055 (0.047-0.064) ng/mL, 0.522 (0.401-0.678) ng/mL, and 0.485 (0.280
      0.0840) ng/mL respectively. Public efforts to reduce exposure to SHS at home
      should be strengthened.

PMID- 25965002
TI  - Oxidative stress in bacteria (Pseudomonas putida) exposed to nanostructures of
      silicon carbide.
AB  - Silicon carbide (SiC) nanostructures produced by combustion synthesis can cause
      oxidative stress in the bacterium Pseudomonas putida. The results of this study
      showed that SiC nanostructures damaged the cell membrane, which can lead to
      oxidative stress in living cells and to the loss of cell viability. As a
      reference, micrometric SiC was also used, which did not exhibit toxicity toward
      cells. Oxidative stress was studied by analyzing the activity of peroxidases, and
      the expression of the glucose-6-phosphate dehydrogenase gene (zwf1) using real
      time PCR and northern blot techniques. Damage to nucleic acid was studied by
      isolating and hydrolyzing plasmids with the formamidopyrimidine [fapy]-DNA
      glycosylase (also known as 8-oxoguanine DNA glycosylase) (Fpg), which is able to
      detect damaged DNA. The level of viable microbial cells was investigated by
      propidium iodide and acridine orange staining. 

PMID- 25965003
TI  - Necrotic cell death induced by the protein-mediated intercellular uptake of CdTe
      quantum dots.
AB  - The toxicity of CdTe QDs with nearly identical maximum emission wavelength but
      modified with four different ligands (MPA, NAC, GSH and dBSA) to HEK293 and HeLa
      cells were investigated using flow cytometry, spectroscopic and microscopic
      methods. The results showed that the cytotoxicity of QDs increased in a dose- and
      time-dependent manner. No appreciable fraction of cells with sub-G1 DNA content,
      the loss of membrane integrity, and the swelling of nuclei clearly indicated that
      CdTe QDs could lead to necrotic cell death in HEK293 cells. JC-1 staining and TEM
      images confirmed that QDs induced MPT, which resulted in mitochondrial swelling,
      collapse of the membrane potential. MPT is an important step in QDs-induced
      necrosis. Moreover, QDs induced MPT through the elevation of ROS. The
      fluorimetric assay and theoretical analysis demonstrated ROS production has been
      associated with the internalization of QDs with cells. Due to large
      surface/volume ratios of QDs, when QDs added in the culture medium, serum
      proteins in the culture medium will be adsorbed on the surface of QDs. This
      adsorption of serum protein will change the surface properties and size, and then
      mediate the cellular uptake of QDs via the clathrin-mediated endocytic pathway.
      After entering into cells, the translocation of QDs in cells is usually via
      endosomal or lysosomal vesicles. The rapid degradation of QDs in lysosome and the
      lysosomal destabilization induce cell necrosis. This study provides a basis for
      understanding the cytotoxicity mechanism of CdTe QDs, and valuable information
      for safe use of QDs in the future. 

PMID- 25965004
TI  - Toxicity and bioaccumulation of bromadiolone to earthworm Eisenia fetida.
AB  - Bromadiolone, a potent second-generation anticoagulant rodenticide, has been
      extensively used worldwide for the field control of rodents. Invertebrates may be
      at risk from primary poisoning as a result of bromadiolone bait applications.
      However, there are few data regarding the toxicity and bioaccumulation of
      bromadiolone to earthworms. In this study, we reported that bromadiolone was
      toxic to earthworms at 1mg/kg soil, which is a likely concentration in the field
      following application of bromadiolone baits. Exposure to bromadiolone resulted in
      a significant inhibition of earthworm growth. The antioxidant activities of
      superoxide dismutase and catalase were slightly increased in earthworms, while
      malondialdehyde content (as a molecular marker indicative of the damage to lipid
      peroxidation) was dominantly elevated over the duration of exposure. Bromadiolone
      in soil is bioaccumulative to earthworms. The biota to soil accumulation factors
      (BSAFs) of bromadiolone were concentration dependent and BSAFs decreased as the
      level of bromadiolone in soil increased. These results suggest earthworms are not
      only the potential subject to primary poisoning but also the source of secondary
      exposure for insectivores and scavengers following application of bromadiolone. 

PMID- 25965005
TI  - Multibiomarker in fish to evaluate a river used to water public supply.
AB  - We aimed to evaluate the ecological integrity of a large river, which receives
      agricultural and urban effluents and is used to water public supply. The fish
      species Astyanax bifasciatus was used as bioindicator during winter and spring
      2012, and summer 2013 at the Middle Iguacu River basin in Parana state, Brazil.
      Water chemical and physical measures and ecotoxicological tests were carried out
      as well biochemical and genetic biomarkers in sampled fish in each period. The
      studied area was divided in three sample points: SP1, located where the water is
      collected to public supply; SP2, located in an urbanized area, and SP3, located
      at an urbanized area with the discharge of the sewage treatment. Although water
      chemical and physical analyzes were range of the Brazilian law to hydric bodies,
      anticholinesterasic effects were found in winter, oxidative stress in summer and
      spring. The higher genotoxic effect was in winter to all sample points. The
      temporal variation in biomarkers and the detection of caffeine in the water call
      attention to the water quality in this river mainly to be used to public supply. 

PMID- 25965006
TI  - Isolation of a Hemagglutinin with Potent Antiproliferative Activity and a Large
      Antifungal Defensin from Phaseolus vulgaris cv. Hokkaido Large Pinto Beans.
AB  - Lectins (hemagglutinins) are defined as sugar-binding proteins or glycoproteins
      with various biological activities. A 60 kDa dimeric hemagglutinin with a blocked
      N-terminus was isolated in large yield (190 mg/60 g) from the common edible bean
      Phaseolus vulgaris cv. Hokkaido large pinto bean. Its hemagglutinating,
      antifungal, and antitumor activities as well as the effects of carbohydrate and
      metal ions on its hemagglutinating activity were examined. It inhibited the
      proliferation of nasopharyngeal carcinoma (CNE2), human breast cancer (MCF7), and
      hepatoma (HepG2) cells. The IC50 values toward HepG2, MCF7, and CNE2 cells after
      treatment for 48 h were 8.1, 6.07, and 7.49 MUM, respectively, which were
      relatively low among lectins of different P. vulgaris cultivars. From the pinto
      beans, a 10888 Da antifungal peptide with similarity to plant defensins as
      revealed by mass spectroscopic analysis was also isolated with a yield of 3.2 mg
      of proteins from 60 g of beans. The large defensin was capable of inhibiting
      mycelial growth in Mycosphaerella arachidicola, Setosphaeria turcica, Bipolaris
      maydis, and Fusarium oxysporum but not in Valsa mali. 

PMID- 25965007
TI  - The role of consensus and culture in children's imitation of inefficient actions.
AB  - A significant body of work has demonstrated children's imitative abilities when
      learning novel actions. Although some research has examined the role of cultural
      background in children's imitation of inefficient actions, to our knowledge no
      research has explored how culture and conformity interact when engaging in
      imitation. In Study 1, 87 Caucasian American and Chinese American preschoolers
      were presented with either one model or three models performing an inefficient
      action. Whereas there were no cultural differences in imitation in the Single
      Model condition, Chinese Americans were significantly more likely to copy the
      model's preference for an inefficient tool in the Consensus condition. Children's
      tool choice was associated with their justification for their choice as well as
      their memory for the model's action. Study 2 explored the impact of immigration
      status on the cultural differences in children's tool choice by including 16
      first-generation Caucasian American children. When comparing the findings with
      the rates from Study 1, both groups of Caucasian American preschoolers imitated
      at rates significantly lower than the Chinese American preschoolers. We suggest
      that the tool choices of Caucasian American children relate to a tendency to
      engage in a perceptually driven mode of learning, whereas the choices of the
      Chinese American children reflect a greater likelihood to use a socially driven
      mode. 

PMID- 25965008
TI  - Prospective study of sentinel node biopsy for high-risk cutaneous squamous cell
      carcinoma of the head and neck.
AB  - BACKGROUND: Nodal metastasis from cutaneous squamous cell carcinoma (SCC) is
      poorly predicted clinically and is associated with a high mortality rate.
      METHODS: From 2010 to 2013, patients with high-risk cutaneous SCC were assessed
      with sentinel node biopsy (SNB) either at the time of primary cutaneous tumor
      resection or at secondary wide local excision. RESULTS: Of 57 patients, 8 (14%)
      had nodal metastasis. Significant predictors of metastasis are the number of high
      risk factors (p = .008), perineural invasion (PNI; p = .05), and lymphovascular
      invasion (LVI; p = .05). During a mean of 19.4 months, 9 patients developed
      recurrence and 6 died of cutaneous SCC, indicating that over 1300 patients would
      be required for a randomized controlled trial with 80% power to detect a
      significant difference in disease-free survival. CONCLUSION: Lymph node
      metastasis occurs in 14% of patients with high-risk cutaneous SCC. Larger studies
      will be required to identify which "high-risk" factors should be considered as an
      indication for surgical assessment of the nodal basin. (c) 2015 Wiley
      Periodicals, Inc. Head Neck 38: E884-E889, 2016.

PMID- 25965009
TI  - When one becomes more: minimum renal artery length in laparoscopic live donor
      nephrectomy.
AB  - BACKGROUND: Laparoscopic donor nephrectomy may convert short main arteries into
      multiple arteries, increasing the technical challenge of implantation. We
      evaluated our experience to identify factors predictive of multiple arteries
      after laparoscopic nephrectomy. METHODS: All laparoscopic nephrectomies from the
      start of our program in November 2002 until June 2013 were studied, and
      preoperative imaging reviewed for donor artery length and multiplicity together
      with operative findings. RESULTS: A total of 287 consecutive laparoscopic live
      donor nephrectomies (64 right and 223 left nephrectomies) were studied. Renal
      artery length was measured from preoperative donor magnetic resonance or computed
      tomography angiogram and nephrectomy performed using a laparoscopic stapling
      device. Nine left kidneys with a single artery (6, 7, 9, 10, 11, 12, 13, 14, and
      16 mm in length) and five right kidneys with a single artery (5, 13, 15, 20, and
      26 mm) on imaging resulted in multiple renal arteries at implantation. Complex
      renal vein anatomy was associated with multiple arteries following retrieval.
      CONCLUSION: A main renal artery length of more than 16 mm on the left and 26 mm
      on the right is unlikely to result in multiple arteries to implant. The
      possibility of multiple arteries should be borne in mind when the donor renal
      artery is short.

PMID- 25965011
TI  - Selective-area growth of GaN nanocolumns on Si(111) substrates for application to
      nanocolumn emitters with systematic analysis of dislocation filtering effect of
      nanocolumns.
AB  - The growth of highly uniform arrays of GaN nanocolumns with diameters from 122 to
      430 nm on Si (111) substrates was demonstrated. The employment of GaN film
      templates with flat surfaces (root mean square surface roughness of 0.84 nm),
      which were obtained using an AlN/GaN superlattice (SL) buffer on Si, contributed
      to the high-quality selective-area growth of nanocolumns using a thin Ti mask of
      5 nm thickness by rf-plasma-assisted molecular beam epitaxy. Although the GaN
      template included a large number of dislocations (dislocation density ~10(11) cm(
      2)), the dislocation filtering effect of nanocolumns was enhanced with decreasing
      nanocolumn diameters (D). Systematic transmission electron microscopy (TEM)
      observation enabled us to explain the dependence of the dislocation propagation
      behavior in nanocolumns on the nanocolumn diameter for the first time. Plan-view
      TEM analysis was performed for nanocolumns with D = 120-324 nm by slicing the
      nanocolumns horizontally at a height of ~300 nm above their bottoms and
      dislocation propagation through the nanocolumns was analyzed by the cross
      sectional TEM observation of nanocolumns with D ~ 200 nm. It was clarified that
      dislocations were effectively filtered in the bottom 300 nm region of the
      nanocolumns, the dislocation density of the nanocolumns decreased with decreasing
      D, and for narrow nanocolumns with D < 200 nm, dislocation-free crystals were
      obtained in the upper part of the nanocolumns. The dramatic improvement in the
      emission properties of GaN nanocolumns observed with decreasing diameter is
      discussed in relation to the decreased dislocation density. The laser action of
      InGaN/GaN-based nanocolumn arrays with a nanocolumn diameter of 170 nm and a
      period of 200 nm on Si under optical excitation was obtained with an emission
      wavelength of 407 nm. We also fabricated red-emitting InGaN-based nanocolumn
      light-emitting diodes on Si that operated at a wavelength of 652 nm,
      demonstrating vertical conduction through the AlN/GaN SL buffer to the Si
      substrate. 

PMID- 25965010
TI  - High-Resolution Mass Spectrometry Based Proteomic Analysis of the Response to
      Vancomycin-Induced Cell Wall Stress in Streptomyces coelicolor A3(2).
AB  - Understanding how bacteria survive periods of cell wall stress is of fundamental
      interest and can help generate ideas for improved antibacterial treatments. In
      this study we use tandem mass tagging to characterize the proteomic response of
      vancomycin resistant Streptomyces coelicolor to the exposure to sublethal levels
      of the antibiotic. A common set of 804 proteins were identified in triplicate
      experiments. Contrasting changes in the abundance of proteins closely associated
      with the cytoplasmic membrane with those taking place in the cytosol identified
      aspects of protein spatial localization that are associated with the response to
      vancomycin. Enzymes for peptidoglycan precursor, mycothiol, ectoine and
      menaquinone biosynthesis together with a multisubunit nitrate reductase were
      recruited to the membrane following vancomycin treatment. Many proteins with
      regulatory functions (including sensor protein kinases) also exhibited
      significant changes in abundance exclusively in the membrane-associated protein
      fraction. Several enzymes predicted to be involved in extracellular peptidoglycan
      crossbridge formation became significantly depleted from the membrane. A
      comparison with data previously acquired on the changes in gene transcription
      following vancomycin treatment identified a common high-confidence set of changes
      in gene expression. Generalized changes in protein abundance indicate roles for
      proteolysis, the pentose phosphate pathway and a reorganization of amino acid
      biosynthesis in the stress response. 

PMID- 25965012
TI  - Temperature and developmental responses of body and cell size in Drosophila;
      effects of polyploidy and genome configuration.
AB  - Increased adult body size in Drosophila raised at lower temperatures could be
      attributed both to an increase in the cell volume and cell number. It is not
      clear, however, whether increased cell size is related to (or even caused by)
      increased nuclear volume and genome size (or configuration). Experiments with
      Drosophila melanogaster stocks (Oregon-R and w1118) raised at 16, 22, 24, and 28
      degrees C resulted in larger adult body and wing size with lower temperature,
      while eye size was less affected. The increase in wing size reflected an increase
      in cell size in both males and females of both stocks. The nucleus size, genome
      size, and DNA condensation of adult flies, embryos, and Schneider 2 cells (S2
      cells, of larval origin) were estimated by flow cytometry. In both adult flies
      and S2 cells, both nucleus size and DNA condensation varied with temperature,
      while DNA content appears to be constant. From 12% to 18% of the somatic cells
      were tetraploid (4C) and 2-5% were octoploid (8C), and for the Oregon strain we
      observed an increase in the fraction of polyploid cells with decreasing
      temperature. The observed increase in body size (and wing size) at low
      temperatures could partly be linked with the cell size and DNA condensation,
      while corresponding changes in the haploid genome size were not observed. 

PMID- 25965013
TI  - Core and body surface temperatures of nesting leatherback turtles (Dermochelys
      coriacea).
AB  - Leatherback turtles (Dermochelys coriacea) are the largest species of marine
      turtle and the fourth most massive extant reptile. In temperate waters they
      maintain body temperatures higher than surrounding seawater through a combination
      of insulation, physiological, and behavioural adaptations. Nesting involves
      physical activity in addition to contact with warm sand and air, potentially
      presenting thermal challenges in the absence of the cooling effect of water, and
      data are lacking with which to understand their nesting thermal biology. Using
      non-contact methods (thermal imaging and infrared thermometry) to avoid any
      stress-related effects, we investigated core and surface temperature during
      nesting. The mean+/-SE core temperature was 31.4+/-0.05 degrees C (newly emerged
      eggs) and was not correlated with environmental conditions on the nesting beach.
      Core temperature of leatherbacks was greater than that of hawksbill turtles
      (Eretmochelys imbricata) nesting at a nearby colony, 30.0+/-0.13 degrees C. Body
      surface temperatures of leatherbacks showed regional variation, the lateral and
      dorsal regions of the head were warmest while the carapace was the coolest
      surface. Surface temperature increased during the early nesting phases, then
      levelled off or decreased during later phases with the rates of change varying
      between body regions. Body region, behavioural phase of nesting and air
      temperature were found to be the best predictors of surface temperature. Regional
      variation in surface temperature were likely due to alterations in blood supply,
      and temporal changes in local muscular activity of flippers during the different
      phases of nesting. Heat exchange from the upper surface of the turtle was
      dominated by radiative heat loss from all body regions and small convective heat
      gains to the carapace and front flippers. 

PMID- 25965014
TI  - Quantification of the effect of electrical and thermal parameters on
      radiofrequency ablation for concentric tumour model of different sizes.
AB  - Radiofrequency ablation (RFA) has been increasingly used in treating cancer for
      multitude of situations in various tissue types. To perform the therapy safely
      and reliably, the effect of critical parameters needs to be known beforehand.
      Temperature plays an important role in the outcome of the therapy and any
      uncertainties in temperature assessment can be lethal. This study presents the
      RFA case of fixed tip temperature where we've analysed the effect of electrical
      conductivity, thermal conductivity and blood perfusion rate of the tumour and
      surrounding normal tissue on the radiofrequency ablation. Ablation volume was
      chosen as the characteristic to be optimised and temperature control was achieved
      via PID controller. The effect of all 6 parameters each having 3 levels was
      quantified with minimum number of experiments harnessing the fractional factorial
      characteristic of Taguchi's orthogonal arrays. It was observed that as the blood
      perfusion increases the ablation volume decreases. Increasing electrical
      conductivity of the tumour results in increase of ablation volume whereas
      increase in normal tissue conductivity tends to decrease the ablation volume and
      vice versa. Likewise, increasing thermal conductivity of the tumour results in
      enhanced ablation volume whereas an increase in thermal conductivity of the
      surrounding normal tissue has a debilitating effect on the ablation volume and
      vice versa. With increase in the size of the tumour (i.e., 2-3cm) the effect of
      each parameter is not linear. The parameter effect varies with change in size of
      the tumour that is manifested by the different gradient observed in ablation
      volume. Most important is the relative insensitivity of ablation volume to blood
      perfusion rate for smaller tumour size (2cm) that is also in accordance with the
      previous results presented in literature. These findings will provide initial
      insight for safe, reliable and improved treatment planning perceptively. 

PMID- 25965015
TI  - Differential metabolism of brown adipose tissue in newborn rabbits in relation to
      position in the litter huddle.
AB  - Competition for resources can contribute importantly to the early development of
      individual differences in behavioral and physiological phenotypes. In newborn
      rabbits, littermates compete for thermally favorable positions within the litter
      huddle. As brown adipose tissue (BAT) is the principal site of thermogenesis in
      such altricial young, we investigated differences in rabbit pups' growth and
      morphological differences in BAT associated with position within the huddle. We
      formed three treatment groups (7 litters/group): GI-birth (pups killed at birth);
      GII-chronic thermal challenge (pups killed after exposure to a moderately cold
      environmental during postnatal days 1-3); GIII-acute thermal challenge (as for
      GII but pups killed after an additional 30min exposure to a very cold environment
      on postnatal day 3). Interscapular BAT was removed at death for histological
      analysis, and triglyceride concentrations measured in serum. Pups occupying
      central positions in the huddle had higher skin temperatures, obtained more milk,
      and were more efficient at converting this into body mass, than pups occupying
      peripheral positions. There was no significant difference in BAT morphology or
      triglyceride concentrations between pups at birth, nor between central and
      peripheral pups chronically exposed to moderate cold until postnatal day 3.
      However, during acute cold exposure at this age, peripheral pups were less able
      to maintain their body temperature, they depleted BAT fat reserves almost
      completely, and they had lower serum concentrations of triglycerides than central
      pups. These findings confirm the contribution of early sibling relations to
      individual differences in growth and metabolic processes associated with
      thermoregulation in newborn rabbits. 

PMID- 25965016
TI  - Three dimensional printing as an effective method of producing anatomically
      accurate models for studies in thermal ecology.
AB  - Hollow copper models painted to match the reflectance of the animal subject are
      standard in thermal ecology research. While the copper electroplating process
      results in accurate models, it is relatively time consuming, uses caustic
      chemicals, and the models are often anatomically imprecise. Although the
      decreasing cost of 3D printing can potentially allow the reproduction of highly
      accurate models, the thermal performance of 3D printed models has not been
      evaluated. We compared the cost, accuracy, and performance of both copper and 3D
      printed lizard models and found that the performance of the models were
      statistically identical in both open and closed habitats. We also find that 3D
      models are more standard, lighter, durable, and inexpensive, than the copper
      electroformed models. 

PMID- 25965017
TI  - Estimation of the core temperature control during ambient temperature changes and
      the influence of circadian rhythm and metabolic conditions in mice.
AB  - It has been speculated that the control of core temperature is modulated by
      physiological demands. We could not prove the modulation because we did not have
      a good method to evaluate the control. In the present study, the control of core
      temperature in mice was assessed by exposing them to various ambient temperatures
      (Ta), and the influence of circadian rhythm and feeding condition was evaluated.
      Male ICR mice (n=20) were placed in a box where Ta was increased or decreased
      from 27 degrees C to 40 degrees C or to -4 degrees C (0.15 degrees C/min) at 0800
      and 2000 (daytime and nighttime, respectively). Intra-abdominal temperature
      (Tcore) was monitored by telemetry. The relationship between Tcore and Ta was
      assessed. The range of Ta where Tcore was relatively stable (range of
      normothermia, RNT) and Tcore corresponding to the RNT median (regulated Tcore)
      were estimated by model analysis. In fed mice, the regression slope within the
      RNT was smaller in the nighttime than in the daytime (0.02 and 0.06,
      respectively), and the regulated Tcore was higher in the nighttime than in the
      daytime (37.5 degrees C and 36.0 degrees C, respectively). In the fasted mice,
      the slope remained unchanged, and the regulated Tcore decreased in the nighttime
      (0.05 and 35.9 degrees C, respectively), while the slopes in the daytime became
      greater (0.13). Without the estimating individual thermoregulatory response such
      as metabolic heat production and skin vasodilation, the analysis of the Ta-Tcore
      relationship could describe the character of the core temperature control. The
      present results show that the character of the system changes depending on time
      of day and feeding conditions. 

PMID- 25965018
TI  - Expression profiling of major heat shock protein genes during different seasons
      in cattle (Bos indicus) and buffalo (Bubalus bubalis) under tropical climatic
      condition.
AB  - Heat shock proteins consist of highly conserved stress proteins, expressed in
      response to stress and play crucial roles in environmental stress tolerance and
      adaptation. The present study was conducted to identify major types of genes
      under the HSP70 family and other HSPs and to evaluate their expression pattern in
      Sahiwal and Tharparkar breeds of zebu cattle (Bos indicus) and Murrah buffalo
      (Bubalus bubalis) with respect to different seasons. Quantitative real time
      polymerase chain reaction was performed to analyze the transcript variants of
      three HSP70 family genes (HSPA1A, HSPA1B, and HSPA8) and HSP10, HSP60, HSP90 and
      HSF1 in each breed. The major finding of this study was the higher abundance of
      all the studied HSP genes during summer and winter compared to spring season, but
      the magnitude of increase was higher during summer as compared to winter. HSPA1A
      and HSPA1B genes showed maximal induction (P<0.001) during summer and winter
      while HSP60 and HSP10 were found to be the second most abundantly expressed HSPs.
      The relative mRNA abundance of HSF1 significantly increased (P<0.001) in Murrah
      buffalo compared to Tharparkar and Sahiwal cattle during summer and winter.
      Expression pattern of heat shock protein genes indicated that amongst the breeds,
      the expression was higher in Murrah buffalo compared to Sahiwal and Tharparkar
      cattle, thereby indicating the more adaptive capacity of later during periods of
      stress. Hence, this study suggests that heat shock protein genes may be
      conveniently used as biomarkers for assessing stress response in cattle and
      buffalo and the expression is species and breed-specific. Furthermore, the
      variation in expression is associated with heat tolerance and adaptation to
      different climatic conditions. 

PMID- 25965019
TI  - Suitability of frequency modulated thermal wave imaging for skin cancer detection
      A theoretical prediction.
AB  - A theoretical study on the quantification of surface thermal response of
      cancerous human skin using the frequency modulated thermal wave imaging (FMTWI)
      technique has been presented in this article. For the first time, the use of the
      FMTWI technique for the detection and the differentiation of skin cancer has been
      demonstrated in this article. A three dimensional multilayered skin has been
      considered with the counter-current blood vessels in individual skin layers along
      with different stages of cancerous lesions based on geometrical, thermal and
      physical parameters available in the literature. Transient surface thermal
      responses of melanoma during FMTWI of skin cancer have been obtained by
      integrating the heat transfer model for biological tissue along with the flow
      model for blood vessels. It has been observed from the numerical results that,
      flow of blood in the subsurface region leads to a substantial alteration on the
      surface thermal response of the human skin. The alteration due to blood flow
      further causes a reduction in the performance of the thermal imaging technique
      during the thermal evaluation of earliest melanoma stages (small volume) compared
      to relatively large volume. Based on theoretical study, it has been predicted
      that the method is suitable for detection and differentiation of melanoma with
      comparatively large volume than the earliest development stages (small volume).
      The study has also performed phase based image analysis of the raw thermograms to
      resolve the different stages of melanoma volume. The phase images have been found
      to be clearly individuate the different development stages of melanoma compared
      to raw thermograms. 

PMID- 25965020
TI  - Impact of fluctuating temperatures on development of the koinobiont
      endoparasitoid Venturia canescens.
AB  - The effect of temperature on the biology of Venturia canescens (Gravenhorst)
      (Hymenoptera: Ichneumonidae) is well understood under constant temperature
      conditions, but less so under more natural, fluctuating conditions. Herein we
      studied the influence of fluctuating temperatures on biological parameters of V.
      canescens. Parasitized fifth-instar larvae of Ephestia kuehniella Zeller
      (Lepidoptera: Pyralidae) were reared individually in incubators at six
      fluctuating temperature regimes (15-19.5 degrees C with a mean of 17.6 degrees C,
      17.5-22.5 degrees C with a mean of 19.8 degrees C, 20-30 degrees C with a mean of
      22.7 degrees C, 22.5-27.5 degrees C with a mean of 25 degrees C, 25.5-32.5
      degrees C with a mean of 28.3 degrees C and 28.5-33 degrees C with a mean of 30
      degrees C) until emergence and death of V. canescens adults. Developmental time
      from parasitism to adult eclosion, adult longevity and survival were recorded at
      each fluctuating temperature regime. In principle, developmental time decreased
      with an increase of the mean temperature of the fluctuating temperature regime.
      Upper and lower threshold temperatures for total development were estimated at
      34.9 and 6.7 degrees C, respectively. Optimum temperature for development and
      thermal constant were 28.6 degrees C and 526.3 degree days, respectively. Adult
      longevity was also affected by fluctuating temperature, as it was significantly
      reduced at the highest mean temperature (7.0 days at 30 degrees C) compared to
      the lowest one (29.4 days at 17.6 degrees C). Survival was low at all tested
      fluctuating temperatures, apart from mean fluctuating temperature of 25 degrees C
      (37%). Understanding the thermal biology of V. canescens under more natural
      conditions is of critical importance in applied contexts. Thus, predictions of
      biological responses to fluctuating temperatures may be used in population
      forecasting models which potentially influence decision-making in IPM programs. 

PMID- 25965021
TI  - Effects of temperature on embryonic and early larval growth and development in
      the rough-skinned newt (Taricha granulosa).
AB  - We investigated the effects of temperature on the growth and development of
      embryonic and early larval stages of a western North American amphibian, the
      rough-skinned newt (Taricha granulosa). We assigned newt eggs to different
      temperatures (7, 14, or 21 degrees C); after hatching, we re-assigned the newt
      larvae into the three different temperatures. Over the course of three to four
      weeks, we measured total length and developmental stage of the larvae. Our
      results indicated a strong positive relationship over time between temperature
      and both length and developmental stage. Importantly, individuals assigned to
      cooler embryonic temperatures did not achieve the larval sizes of individuals
      from the warmer embryonic treatments, regardless of larval temperature. Our
      investigation of growth and development at different temperatures demonstrates
      carry-over effects and provides a more comprehensive understanding of how
      organisms respond to temperature changes during early development. 

PMID- 25965022
TI  - Effect of prenatal temperature conditioning of laying hen embryos: Hatching, live
      performance and response to heat and cold stress during laying period.
AB  - This study was designed to determine the effect of prenatal temperature
      conditioning on hatching and live performance of laying chickens, and response to
      heat and cold stress during laying period. A total of 3600 eggs obtained from
      ATAK-S brown parent stock were incubated at control (37.5 degrees C, CONT-Inc),
      cyclic low (36.5 degrees C/6h/d from 10 to 18d of incubation, LOW-Inc) or high
      (38.5 degrees C/6h/d from 10-18d of incubation, HIGH-Inc) incubation
      temperatures. Hatched chicks per incubation temperature were reared under
      standard rearing conditions up to 26wk. From 27 to 30wk, hens from each
      incubation temperature were divided into 3 environmentally controlled rooms and
      reared at control (20+/-2 degrees C, CONT-Room), low (12+/-2 degrees C, COLDS) or
      high (32+/-2 degrees C, HEATS) temperatures. Hatching performance, body weight,
      egg production, and plasma triiodothyronine (T3) and thyroxine (T4) levels and
      oxidant and antioxidant activities were evaluated. The highest hatchability was
      for LOW-Inc chicks while HIGH-Inc chick had similar hatchability to CONT-Inc.
      There was no effect of incubation temperatures on plasma MDA, GSH-Px, activities
      and T4 concentrations on day of hatch. LOW- Inc chicks had higher SOD activities
      and T3 concentrations compared to the other groups. Although chick weight was
      similar among incubation temperature groups, CONT-Inc chicks were heavier than
      those cyclic incubation temperature groups until 12wk of age. Incubation
      temperature had no effect on sexual maturity age and weight and egg production of
      laying hens. From 27 to 30wk, regardless of incubation temperature, HEATS hens
      lost weight from day 0 to 10, had the highest cloacal temperatures and lowest
      feed consumption and egg production while COLDS hens had the lowest cloacal
      temperatures. At day 5, T4 level was higher in LOW-Inc hens at COLDS but it was
      higher in HIGH-Inc hens at HEATS compared to CONT-Inc. These data may suggest a
      modification in thyroid activity of hens that were conditioned during the
      incubation period. Moreover under COLDS condition, SOD production of LOW-Inc hens
      was higher than those of CONT- and HIGH-Inc hens indicating an induction in
      antioxidant enzyme activity. Nonetheless, prenatal temperature conditioning of
      laying hen embryos had no advantage on laying performance of hens under
      temperature stress conditions. 

PMID- 25965023
TI  - Ice slurry ingestion reduces both core and facial skin temperatures in a warm
      environment.
AB  - Internal body cooling by ingesting ice slurry has recently attracted attention.
      Because ice slurries are ingested through the mouth, it is possible that this
      results in conductive cooling of the facial skin and brain. However, no studies
      have investigated this possibility. Thus, the aim of this study was to
      investigate the effects of ice slurry ingestion on forehead skin temperature at
      the point of conductive cooling between the forehead skin and brain. Eight male
      subjects ingested either 7.5g/kg of ice slurry (-1 degrees C; ICE), a cold sports
      drink (4 degrees C; COOL), or a warm sports drink (37 degrees C; CON) for 15min
      in a warm environment (30 degrees C, 80% relative humidity). Then, they remained
      at rest for 1h. As physiological indices, rectal temperature (Tre), mean skin
      temperature, forehead skin temperature (Thead), heart rate, nude body mass, and
      urine specific gravity were measured. Subjective thermal sensation (TS) was
      measured at 5-min intervals throughout the experiment. With ICE, Tre and Thead
      were significantly reduced compared with CON and COOL conditions (p<0.05). The
      results of the other physiological indices were not significantly different. TS
      with ICE was significantly lower than that with CON and COOL (p<0.05) and was
      correlated with Tre or Thead (p<0.05). These results indicate that ice slurry
      ingestion may induce conductive cooling between forehead skin and brain, and
      reduction in core and forehead skin temperature reduced thermal sensation. 

PMID- 25965024
TI  - Response of body size and developmental time of Tribolium castaneum to constant
      versus fluctuating thermal conditions.
AB  - Temperature has profound effects on biological functions at all levels of
      organization. In ectotherms, body size is usually negatively correlated with
      ambient temperature during development, a phenomenon known as The Temperature
      Size Rule (TSR). However, a growing number of studies have indicated that
      temperature fluctuations have a large influence on life history traits and the
      implications of such fluctuations for the TSR are unknown. Our study investigated
      the effect of different constant and fluctuating temperatures on the body mass
      and development time of red flour beetles (Tribolium castaneum Herbst, 1797); we
      also examined whether the sexes differed in their responses to thermal
      conditions. We exposed the progeny of half-sib families of a T. castaneum
      laboratory strain to one of four temperature regimes: constant 30 degrees C,
      constant 25 degrees C, fluctuating with a daily mean of 30 degrees C, or
      fluctuating with a daily mean of 25 degrees C. Sex-specific development time and
      body mass at emergence were determined. Beetles developed the fastest and had the
      greatest body mass upon emergence when they were exposed to a constant
      temperature of 30 degrees C. This pattern was reversed when beetles experienced a
      constant temperature of 25 degrees C: slowest development and lowest body mass
      upon emergence were observed. Fluctuations changed those effects significantly -
      impact of temperature on development time was smaller, while differences in body
      mass disappeared completely. Our results do not fit TSR predictions. Furthermore,
      regardless of the temperature regime, females acquired more mass, while there
      were no differences between sexes in development time to eclosion. This finding
      fails to support one of the explanations for smaller male size: that selection
      favors the early emergence of males. We found no evidence of genotype *
      environment interactions for selected set of traits. 

PMID- 25965025
TI  - Circannual rhythm of resting metabolic rate of a small Afrotropical bird.
AB  - Seasonal variation in avian metabolic rate is well established in Holarctic and
      temperate species, while trends in Afrotropical species are relatively poorly
      understood. Furthermore, given the paucity of data on circannual rhythm in avian
      metabolism, it is not known whether seasonal measurements made in summer and
      winter correspond with annual peaks and troughs in avian metabolic rate. Thus, we
      investigated how mean body mass, resting metabolic rate (RMR) and evaporative
      water loss (EWL) of a small Afrotropical bird, the Cape white-eye (Zosterops
      virens), changed monthly over the course of a year at 20 degrees C and 25 degrees
      C. Mean body mass was 12.2+/-1.0g throughout the study period. However, both EWL
      and RMR varied monthly, and peaks and troughs in RMR occurred in March and
      October respectively, which did not correspond to peaks and troughs in mean
      monthly outdoor ambient temperatures. These results suggest that measuring RMR at
      the height of summer and winter may underestimate the flexibility of which birds
      are capable in terms of their metabolic rate. We encourage further studies on
      this topic, to establish whether the lag between environmental temperature and
      RMR is consistent in other species. 

PMID- 25965026
TI  - Therapist use of Socratic questioning predicts session-to-session symptom change
      in cognitive therapy for depression.
AB  - Socratic questioning is a key therapeutic strategy in cognitive therapy (CT) for
      depression. However, little is known regarding its relation to outcome. In this
      study, we examine therapist use of Socratic questioning as a predictor of session
      to-session symptom change. Participants were 55 depressed adults who participated
      in a 16-week course of CT (see Adler, Strunk, & Fazio, 2015). Socratic
      questioning was assessed through observer ratings of the first three sessions.
      Socratic ratings were disaggregated into scores reflecting within-patient and
      between-patient variability to facilitate an examination of the relation of
      within-patient Socratic questioning and session-to-session symptom change.
      Because we examined within-patient variability in Socratic questioning, the
      identification of such a relation cannot be attributed to any stable patient
      characteristics that might otherwise introduce a spurious relation. Within
      patient Socratic questioning significantly predicted session-to-session symptom
      change across the early sessions, with a one standard deviation increase in
      Socratic-Within predicting a 1.51-point decrease in BDI-II scores in the
      following session. Within-patient Socratic questioning continued to predict
      symptom change after controlling for within-patient ratings of the therapeutic
      alliance (i.e., Relationship and Agreement), suggesting that the relation of
      Socratic questioning and symptom change was not only independent of stable
      characteristics, but also within-patient variation in the alliance. Our results
      provide the first empirical support for a relation of therapist use of Socratic
      questioning and symptom change in CT for depression. 

PMID- 25965027
TI  - Mapping paddy rice planting area in wheat-rice double-cropped areas through
      integration of Landsat-8 OLI, MODIS, and PALSAR images.
AB  - As farmland systems vary over space and time (season and year), accurate and
      updated maps of paddy rice are needed for studies of food security and
      environmental problems. We selected a wheat-rice double-cropped area from
      fragmented landscapes along the rural-urban complex (Jiangsu Province, China) and
      explored the potential utility of integrating time series optical images (Landsat
      8, MODIS) and radar images (PALSAR) in mapping paddy rice planting areas. We
      first identified several main types of non-cropland land cover and then
      identified paddy rice fields by selecting pixels that were inundated only during
      paddy rice flooding periods. These key temporal windows were determined based on
      MODIS Land Surface Temperature and vegetation indices. The resultant paddy rice
      map was evaluated using regions of interest (ROIs) drawn from multiple high
      resolution images, Google Earth, and in-situ cropland photos. The estimated
      overall accuracy and Kappa coefficient were 89.8% and 0.79, respectively. In
      comparison with the National Land Cover Data (China) from 2010, the resultant map
      better detected changes in the paddy rice fields and revealed more details about
      their distribution. These results demonstrate the efficacy of using images from
      multiple sources to generate paddy rice maps for two-crop rotation systems. 

PMID- 25965028
TI  - Casimir physics.

PMID- 25965029
TI  - Hydrophobic Encapsulated Phosphonium Salts-Synthesis of Weakly Coordinating
      Cations and their Application in Wittig Reactions.
AB  - Large and rigid tetraarylphosphonium tetrafluoroborate salts have been
      synthesized representing weakly coordinating cations with diameters of several
      nanometers. Divergent dendritic growth by means of thermal Diels-Alder
      cycloaddition was employed for the construction of the hydrophobic polyphenylene
      framework up to the third generation. X-ray crystal structure analysis of first
      generation phosphonium tetrafluoroborate supported the rigidity of the non
      collapsible shell around the phosphorus center and gave insight into solid-state
      packing and cation-anion distances. Copper(I)-catalyzed azide-alkyne ligation
      served as reliable method for the preparation of a first-generation
      triazolylphenyl hybrid phosphonium cation under mild reaction conditions.
      Furthermore, from the synthesis of triarylbenzylphosphonium bromides, Wittig
      precursors with unprecedented bulky substituents in the alpha-position were
      accessible. Employment of these precursors under Wittig conditions by treatment
      with base and subsequent reaction with aldehydes preferentially provided (Z)
      olefins with bulky polyphenylene substituents. 

PMID- 25965030
TI  - Promotion of bone regeneration.

PMID- 25965031
TI  - Disruption of the rainbow trout reproductive endocrine axis by the polycyclic
      aromatic hydrocarbon benzo[a]pyrene.
AB  - Successful reproduction in salmonids depends on a complex and highly regulated
      interplay between the pharmacokinetics and pharmacodynamics of naturally
      circulating sex steroids. The effects of a single intraperitoneal administration
      of the model PAH benzo[a]pyrene (B[a]P) on the kinetics of circulating levels of
      estradiol and testosterone through 7d post-injection in mature male and female
      rainbow trout (Oncorhynchus mykiss) in pre-spawning and spawning condition were
      investigated. Detailed measurements of the time course of injected E2 and
      excretion into the bile followed by pharmacokinetic modeling techniques were used
      to aid in identifying the potential mechanism of ED caused by B[a]P exposure.
      Plasma E2 and T concentrations were reduced significantly in both male and female
      trout. Administration of the GnRH analogue des-Gly(10)[D-Ala(6)]LH-RH-ethylamide,
      to induce spawning steroid profiles increased plasma E2 concentrations in control
      females, but not in B[a]P-treated fish. The mechanism underlying reductions in
      sex steroids in pre-spawning and spawning salmonids appears to be unrelated to
      the induction of P450 and related biotransformation enzymes by B[a]P. Induced
      biotransformation enzyme activities did not result in altered [(3)H]estradiol
      pharmacokinetics (e.g. terminal half-life) or elimination of steroid in bile,
      suggesting that B[a]P alters plasma E2 and T concentrations by other ED
      mechanisms in an anti-estrogenic manner. 

PMID- 25965032
TI  - Unlocking Inter- to Non-Penetrating Frameworks Using Steric Influences on Spacers
      for CO2 Adsorption.
AB  - Four porous coordination networks have been synthesized from 1,4
      benzenedicarboxylate with Cl, Br, I, and NO2 substituents whose different spatial
      differences are sufficient to influence the coordination mode of adjacent
      carboxyl moieties to unlock an inter-penetrating framework to give isostructural
      structures. Their size and polarity differences account for the diverging CO2
      adsorption performances. 

PMID- 25965033
TI  - Assessing determinants of maternal blood concentrations for persistent organic
      pollutants and metals in the eastern and western Canadian Arctic.
AB  - Aboriginal peoples in the Canadian Arctic are exposed to persistent organic
      pollutants (POPs) and metals mainly through their consumption of a traditional
      diet of wildlife items. Recent studies indicate that many human chemical levels
      have decreased in the north, likely due to a combination of reduced global
      chemical emissions, dietary shifts, and risk mitigation efforts by local health
      authorities. Body burdens for chemicals in mothers can be further offset by
      breastfeeding, parity, and other maternal characteristics. We have assessed the
      impact of several dietary and maternal covariates following a decade of awareness
      of the contaminant issue in northern Canada, by performing multiple stepwise
      linear regression analyses from blood concentrations and demographic variables
      for 176 mothers recruited from Nunavut and the Northwest Territories during the
      period 2005-2007. A significant aboriginal group effect was observed for the
      modeled chemicals, except for lead and cadmium, after adjusting for covariates.
      Further, blood concentrations for POPs and metals were significantly associated
      with at least one covariate of older age, fewer months spent breastfeeding, more
      frequent eating of traditional foods, or smoking during pregnancy. Cadmium had
      the highest explained variance (72.5%) from just two significant covariates
      (current smoking status and parity). Although Inuit participants from the
      Northwest Territories consumed more traditional foods in general, Inuit
      participants from coastal communities in Nunavut continued to demonstrate higher
      adjusted blood concentrations for POPs and metals examined here. While this is
      due in part to a higher prevalence of marine mammals in the eastern Arctic diet,
      it is possible that other aboriginal group effects unrelated to diet may also
      contribute to elevated chemical body burdens in Canadian Arctic populations. 

PMID- 25965034
TI  - Binding interactions between suberin monomer components and pesticides.
AB  - Understanding the role of biomacromolecules and their interactions with
      pollutants is a key for elucidating the sorption mechanisms and making an
      accurate assessment of the environmental fate of pollutants. The knowledge of the
      sorption properties of the different constituents of these biomacromolecules may
      furnish a significant contribution to this purpose. Suberin is a very abundant
      biopolymer in higher plants. In this study, suberin monomers isolated from cork
      were analyzed by thermally-assisted methylation with tetramethylammonium
      hydroxide (TMAH) in a pyrolysis unit coupled to gas chromatography-mass
      spectrometry (GC/MS). The isolated monomer mixture was used to study the sorption
      of three pesticides (isoproturon, methomyl and oxamyl). The modes of pesticide
      sorbent interactions were analyzed by means of two modeling calculations, the
      first one representing only the mixture of suberin monomers used in the sorption
      study, and the second one including glycerol to the mixture of suberin monomers,
      as a building block of the suberin molecule. The results indicated that the
      highest sorption capacity exhibited by the sorbent was for isoproturon (33%)
      being methomyl and oxamyl sorbed by the main suberin components to a lesser
      extent (3% and<1%, respectively). In addition to van der Waals interactions with
      the apolar region of sorbent and isoproturon, modeling calculations evidenced the
      formation of a hydrogen bond between the isoproturon NH group and a carboxylic
      oxygen atom of a suberin monomer. In the case of methomyl and oxamyl only weak
      van der Waals interactions stabilize the pesticide-sorbent adducts. The presence
      of glycerol in the model provoked significant changes in the interactions with
      isoproturon and methomyl. 

PMID- 25965035
TI  - Advantages of integrated and sustainability based assessment for metabolism based
      strategic planning of urban water systems.
AB  - Despite providing water-related services as the primary purpose of urban water
      system (UWS), all relevant activities require capital investments and operational
      expenditures, consume resources (e.g. materials and chemicals), and may increase
      negative environmental impacts (e.g. contaminant discharge, emissions to water
      and air). Performance assessment of such a metabolic system may require
      developing a holistic approach which encompasses various system elements and
      criteria. This paper analyses the impact of integration of UWS components on the
      metabolism based performance assessment for future planning using a number of
      intervention strategies. It also explores the importance of sustainability based
      criteria in the assessment of long-term planning. Two assessment approaches
      analysed here are: (1) planning for only water supply system (WSS) as a part of
      the UWS and (2) planning for an integrated UWS including potable water,
      stormwater, wastewater and water recycling. WaterMet(2) model is used to simulate
      metabolic type processes in the UWS and calculate quantitative performance
      indicators. The analysis is demonstrated on the problem of strategic level
      planning of a real-world UWS to where optional intervention strategies are
      applied. The resulting performance is assessed using the multiple criteria of
      both conventional and sustainability type; and optional intervention strategies
      are then ranked using the Compromise Programming method. The results obtained
      show that the high ranked intervention strategies in the integrated UWS are those
      supporting both water supply and stormwater/wastewater subsystems (e.g. rainwater
      harvesting and greywater recycling schemes) whilst these strategies are ranked
      low in the WSS and those targeting improvement of water supply components only
      (e.g. rehabilitation of clean water pipes and addition of new water resources)
      are preferred instead. Results also demonstrate that both conventional and
      sustainability type performance indicators are necessary for strategic planning
      in the UWS. 

PMID- 25965036
TI  - Degradation of 5-FU by means of advanced (photo)oxidation processes: UV/H2O2,
      UV/Fe2+/H2O2 and UV/TiO2--Comparison of transformation products, ready
      biodegradability and toxicity.
AB  - The present study investigates the degradation of the antimetabolite 5
      fluorouracil (5-FU) by three different advanced photo oxidation processes:
      UV/H2O2, UV/Fe(2+)/H2O2 and UV/TiO2. Prescreening experiments varying the H2O2
      and TiO2 concentrations were performed in order to set the best catalyst
      concentrations in the UV/H2O2 and UV/TiO2 experiments, whereas the UV/Fe(2+)/H2O2
      process was optimized varying the pH, Fe(2+) and H2O2 concentrations by means of
      the Box-Behnken design (BBD). 5-FU was quickly removed in all the irradiation
      experiments. The UV/Fe(2+)/H2O2 and UV/TiO2 processes achieved the highest degree
      of mineralization, whereas the lowest one resulted from the UV/H2O2 treatment.
      Six transformation products were formed during the advanced (photo)oxidation
      processes and identified using low and high resolution mass spectrometry. Most of
      them were formed and further eliminated during the reactions. The parent compound
      of 5-FU was not biodegraded, whereas the photolytic mixture formed in the UV/H2O2
      treatment after 256 min showed a noticeable improvement of the biodegradability
      in the closed bottle test (CBT) and was nontoxic towards Vibrio fischeri. In
      silico predictions showed positive alerts for mutagenic and genotoxic effects of
      5-FU. In contrast, several of the transformation products (TPs) generated along
      the processes did not provide indications for mutagenic or genotoxic activity.
      One exception was TP with m/z 146 with positive alerts in several models of
      bacterial mutagenicity which could demand further experimental testing. Results
      demonstrate that advanced treatment can eliminate parent compounds and its
      toxicity. However, transformation products formed can still be toxic. Therefore
      toxicity screening after advanced treatment is recommendable.

PMID- 25965037
TI  - Using gamma distribution to determine half-life of rotenone, applied in
      freshwater.
AB  - Following the use of rotenone to eradicate invasive pest fish, a dynamic first
      order kinetic model is usually used to determine the half-life and rate at which
      rotenone dissipated from the treated waterbody. In this study, we investigate the
      use of a stochastic gamma model for determining the half-life and rate at which
      rotenone dissipates from waterbodies. The first-order kinetic and gamma models
      produced similar values for the half-life (4.45 days and 5.33 days respectively)
      and days to complete dissipation (51.2 days and 52.48 days respectively).
      However, the gamma model fitted the data better and was more flexible than the
      first-order kinetic model, allowing us to use covariates and to predict a
      possible range for the half-life of rotenone. These benefits are particularly
      important when examining the influence that different environmental factors have
      on rotenone dissipation and when trying to predict the rate at which rotenone
      will dissipate during future operations. We therefore recommend that in future
      the gamma distribution model is used when calculating the half-life of rotenone
      in preference to the dynamic first-order kinetics model.

PMID- 25965039
TI  - The influence of tomato processing on residues of organochlorine and
      organophosphate insecticides and their associated dietary risk.
AB  - Due to the increasing food demand, the use of pesticides in agriculture is
      increasing. Particularly in low income countries poor training among farmers,
      combined with the use of obsolete pesticides may result in a high risk for the
      consumers. In this study six organochlorines and five organophosphates were
      analyzed in 54 samples of tomatoes from small scale farmers in Bolivia. The
      analyses were done on unprocessed, stored, washed and peeled tomatoes. The
      cumulated risk associated with consumption of the tomatoes after different
      storage times and processing treatments was evaluated using the Hazard Index (HI)
      for acute risk assessment. All 11 pesticides were detected in the analyses
      although several of them are obsolete and included in the Stockholm convention
      ratified by Bolivia. The organochlorines were found in the MUg pesticide/kg
      tomato range and below the HI, while the organophosphates were present in the mg
      pesticide/kg tomato range and most often above the HI. The low organochlorine
      concentrations were not significantly affected by time or treatment, but storage
      significantly decreased the concentrations of organophosphates. Washing decreased
      the initial concentrations to between 53% (malathion) down to 2% (ethyl
      parathion), while peeling had a larger effect reducing the initial concentrations
      to between 33% (malathion) and 0.7% (chlorpyriphos). Both the acute and chronic
      cumulative risk assessment of organophosphates showed a dietary risk for
      unprocessed tomatoes three days after harvest. For children, also the consumption
      of washed tomatoes constituted a dietary risk. To reduce the dietary risk of
      pesticide residues in Bolivia, there is an urgent need of farmer education and
      introduction of less hazardous pesticides as well as resources for surveillance
      and enforcement of legislation in order to ensure public health.

PMID- 25965040
TI  - A score for measuring health risk perception in environmental surveys.
AB  - BACKGROUND: In environmental surveys, risk perception may be a source of bias
      when information on health outcomes is reported using questionnaires. Using the
      data from a survey carried out in the largest chipboard industrial district in
      Italy (Viadana, Mantova), we devised a score of health risk perception and
      described its determinants in an adult population. METHODS: In 2006, 3697 parents
      of children were administered a questionnaire that included ratings on 7
      environmental issues. Items dimensionality was studied by factor analysis. After
      testing equidistance across response options by homogeneity analysis, a risk
      perception score was devised by summing up item ratings. RESULTS: Factor analysis
      identified one latent factor, which we interpreted as health risk perception,
      that explained 65.4% of the variance of five items retained after scaling. The
      scale (range 0-10, mean +/- SD 9.3 +/- 1.9) had a good internal consistency
      (Cronbach's alpha 0.87). Most subjects (80.6%) expressed maximum risk perception
      (score = 10). Italian mothers showed significantly higher risk perception than
      foreign fathers. Risk perception was higher for parents of young children, and
      for older parents with a higher education, than for their counterparts. Actual
      distance to major roads was not associated with the score, while self-reported
      intense traffic and frequent air refreshing at home predicted higher risk
      perception. CONCLUSIONS: When investigating health effects of environmental
      hazards using questionnaires, care should be taken to reduce the possibility of
      awareness bias at the stage of study planning and data analysis. Including
      appropriate items in study questionnaires can be useful to derive a measure of
      health risk perception, which can help to identify confounding of association
      estimates by risk perception.

PMID- 25965041
TI  - Lesser White-fronted (Anser erythropus) and Greater White-fronted (A. albifrons)
      Geese wintering in Greek wetlands are not threatened by Pb through shot
      ingestion.
AB  - Fecal lead (Pb) levels were investigated in the threatened European population of
      the Lesser White-fronted Goose (LWfG, Anser erythropus) and of the non-threatened
      Greater White-fronted Goose (GWfG, Anser albifrons) wintering in two wetland
      areas in northern Greece in order to assess the potential risk from Pb exposure.
      Fecal, soil and food plant samples were analyzed. Levels of Pb were normalized
      using Al concentrations in order to separate the effect of possible ingestion of
      Pb shot from that of soil or sediment accidentally ingested with food. All
      concentrations are expressed on a dry weight basis. Geometric means of Pb content
      in the feces of LWfG were 6.24 mg/kg at Evros Delta and 7.34 mg/kg at Lake
      Kerkini (maximum values of 28.61 mg/kg and 36.68 mg/kg, respectively); for fecal
      samples of GWfG geometric means were 2.39 mg/kg at Evros Delta and 6.90 mg/kg at
      Kerkini (corresponding maximum values of 25.09 mg/kg and 42.26 mg/kg). Soil Pb
      was in the range of 5.2-60.2mg/kg (geometric mean = 22.6 mg/kg) for the Evros
      Delta and between 13.4 and 64.9 mg/kg (geometric mean=28.1mg/kg) for Kerkini. A
      general linear model fitted to the data showed that Pb levels were very closely
      dependent on Al levels in the feces from both species and at both sites
      indicating soil or sediment were the only significant source of Pb; species and
      site, as well as their interaction, were not statistically significant factors.
      For both species and at both sites exposure to Pb was evidently very mild and the
      observed levels of Pb were well below the proposed thresholds for lethal or
      sublethal effects of Pb poisoning. Soil ingestion appeared to gradually increase
      from October to December for LWfG at Kerkini, corresponding to a gradual
      depletion of their food source.

PMID- 25965038
TI  - Estimation of chronic personal exposure to airborne polycyclic aromatic
      hydrocarbons.
AB  - BACKGROUND: Polycyclic aromatic hydrocarbons (PAH) exposure from solid fuel
      burning represents an important public health issue for the majority of the
      global population. Yet, understanding of individual-level exposures remains
      limited. OBJECTIVES: To develop regionally adaptable chronic personal exposure
      model to pro-carcinogenic PAH (c-PAH) for the population in Krakow, Poland.
      METHODS: We checked the assumption of spatial uniformity in eight c-PAH using the
      coefficients of divergence (COD), a marker of absolute concentration differences.
      Upon successful validation, we developed personal exposure models for eight pro
      carcinogenic PAH by integrating individual-level data with area-level
      meteorological or pollutant data. We checked the resulting model for accuracy and
      precision against home outdoor monitoring data. RESULTS: During winter, COD of
      0.1 for Krakow suggest overall spatial uniformity in the ambient concentration of
      the eight c-PAH. The three models that we developed were associated with index of
      agreement approximately equal to 0.9, root mean square error < 2.6 ng/m(3), and
      90th percentile of absolute difference <= 4 ng/m(3) for the predicted and the
      observed concentrations for eight pro-carcinogenic PAH. CONCLUSIONS: Inexpensive
      and logistically feasible information could be used to estimate chronic personal
      exposure to PAH profiles, in lieu of costly and labor-intensive personal air
      monitoring at wide scale. At the same time, thorough validation through direct
      personal monitoring and assumption checking are critical for successful model
      development.

PMID- 25965042
TI  - Characterization and source identification of sub-micron particles at the HKUST
      Supersite in Hong Kong.
AB  - Particle size distribution measurements were conducted continuously at a 30
      second interval using the Fast Mobility Particle Sizer (FMPS) in August,
      September, November and December of 2011 at a coastal background site in Hong
      Kong. Concurrent measurements of CO, NOx, O3, SO2 and volatile organic compounds
      (VOCs) were used to determine the causes of high particle number concentration
      (PNC) events. In all sampling months, PNC were usually higher in the evening,
      likely resulting from the arrival of upwind air pollutants as wind direction
      changed in the late afternoon. On the more polluted days, the PNC were usually
      higher around noon, particularly in August, similar to the diurnal trend of O3.
      The mode diameter at noon was smaller than in other time periods in all sampling
      months, further highlighting the role of secondary formation at this urban
      background site. A prolonged period of pollution episode occurred in late August.
      High PNC resulted from the arrival of pollution laden air from the PRD region or
      super regions. In December, new particle formation followed by subsequent growth
      accounted for most of the polluted days. Overall, meteorology was the most
      important parameter affecting particle concentrations and formation at this Hong
      Kong background site. 

PMID- 25965043
TI  - Decreasing Kd uncertainties through the application of thermodynamic sorption
      models.
AB  - Radionuclide retardation processes during transport are expected to play an
      important role in the safety assessment of subsurface disposal facilities for
      radioactive waste. The linear distribution coefficient (Kd) is often used to
      represent radionuclide retention, because analytical solutions to the classic
      advection-diffusion-retardation equation under simple boundary conditions are
      readily obtainable, and because numerical implementation of this approach is
      relatively straightforward. For these reasons, the Kd approach lends itself to
      probabilistic calculations required by Performance Assessment (PA) calculations.
      However, it is widely recognised that Kd values derived from laboratory
      experiments generally have a narrow field of validity, and that the uncertainty
      of the Kd outside this field increases significantly. Mechanistic multicomponent
      geochemical simulators can be used to calculate Kd values under a wide range of
      conditions. This approach is powerful and flexible, but requires expert knowledge
      on the part of the user. The work presented in this paper aims to develop a
      simplified approach of estimating Kd values whose level of accuracy would be
      comparable with those obtained by fully-fledged geochemical simulators. The
      proposed approach consists of deriving simplified algebraic expressions by
      combining relevant mass action equations. This approach was applied to three
      distinct geochemical systems involving surface complexation and ion-exchange
      processes. Within bounds imposed by model simplifications, the presented approach
      allows radionuclide Kd values to be estimated as a function of key system
      controlling parameters, such as the pH and mineralogy. This approach could be
      used by PA professionals to assess the impact of key geochemical parameters on
      the variability of radionuclide Kd values. Moreover, the presented approach could
      be relatively easily implemented in existing codes to represent the influence of
      temporal and spatial changes in geochemistry on Kd values. 

PMID- 25965044
TI  - Persistent organic pollutants (POPs) in blubber of common bottlenose dolphins
      (Tursiops truncatus) along the northern Gulf of Mexico coast, USA.
AB  - A number of studies were initiated in response to the Deepwater Horizon (DWH) oil
      spill to understand potential injuries to bottlenose dolphins (Tursiops
      truncatus) that inhabit the northern Gulf of Mexico (NGoM) estuarine waters. As
      part of these studies, remote biopsy skin and blubber samples were collected from
      dolphins at six field sites that received varying degrees of oiling: Barataria
      Bay (BB), Chandeleur Sound West (CSW), Chandeleur Sound East (CSE), Mississippi
      Sound South (MSS), Mississippi Sound North (MSN), and St. Joseph Bay (SJ).
      Blubber samples from 108 male dolphins were analyzed for persistent organic
      pollutant (POP) concentrations, as high levels of POPs have been previously
      reported in other southeastern U.S. dolphins and the potential contribution of
      these compounds to adverse health effects in NGoM dolphins must be considered.
      Dolphin blubber levels of summed POPs (SigmaPOPs) did not differ significantly
      across sites (F-test, P=0.9119) [MUg/g lipid; geometric mean and 95% CI]; CSW
      [65.9 (51.4-84.6)], SJ [74.1 (53.0-104)], MSN [74.3 (58.7-93.9)], BB [75.3 (56.4
      101)], CSE [80.5 (57.8-112)], and MSS [82.5 (65.9-103)]. Overall, POP
      concentrations were in the lower half of the range compared to previously
      reported concentrations from other southeastern U.S. sites. Increased dolphin
      mortalities have been ongoing in the NGoM and have been suggested to be linked
      with the DWH oil spill. In addition, lung disease, impaired adrenal function, and
      serum biochemical abnormalities have been reported in dolphins from BB, an area
      that was heavily oiled. The results of this study suggest that POPs are likely
      not a primary contributor to the poor health conditions and increased mortality
      observed in some populations of NGoM dolphins following the DWH oil spill. 

PMID- 25965045
TI  - Identifying the source of tar balls deposited along the beaches of Goa in 2013
      and comparing with historical data collected along the West Coast of India.
AB  - Deposition of oil residues, also known as tar balls, is a seasonal phenomenon,
      and it occurs only in the southwest monsoon season along the west coast of India.
      This has become a serious environmental issue, as Goa is a global tourist
      destination. The present work aims at identifying the source oil of the tar balls
      that consistently depositing along the Goa coast using multi-marker fingerprint
      technique. In this context, the tar ball samples collected in May 2013 from 9
      beaches of Goa coast and crude oils from different oil fields and grounded ship
      were subject to multi-marker analyses such as n-alkanes, pentacyclic terpanes,
      regular steranes, compound specific isotope analysis (CSIA) and principle
      component analysis (PCA). The n-alkane weathering index shows that samples have
      been weathered to various degrees, and the status of weathering is moderate.
      Since the international tanker route passes closer to the west coast of India
      (WCI), it is generally presumed that tanker wash is the source of the tar balls.
      We found that 2010/2011 tar balls are as tanker wash, but the present study
      demonstrates that the Bombay High (BH) oil fields can also contribute to oil
      contamination (tar balls) along ~ 650 km stretch of the WCI, running from Gujarat
      in the north to Goa in the south. The simulated trajectories show that all the
      particles released in April traveled in the southeast direction, and by May, they
      reached the Goa coast with the influence of circulation of Indian monsoon system.

PMID- 25965046
TI  - Dark production of hydroxyl radicals by aeration of anoxic lake water.
AB  - Lake circulation is an important phenomenon that ensures oxygenation of the water
      column. Here we report that aeration of anoxic hypolimnion water causes
      production of highly reactive hydroxyl radicals (.OH), which are also produced
      photochemically in the epilimnion. Model calculations suggest that the dark
      process of .OH generation can be comparable with photochemical reactions in some
      lake environments, provided that the hypolimnion is a significant fraction of the
      whole lake volume. In these cases, lake overturn could significantly contribute
      to the yearly .OH budget of the lake water and might cause significant
      degradation of some pollutants, for which the reaction with .OH is an important
      removal process from surface waters.

PMID- 25965047
TI  - Detection of glucocorticoid receptor agonists in effluents from sewage treatment
      plants in Japan.
AB  - Glucocorticoids (GCs) are widely used as anti-inflammatory drugs. Our previous
      study demonstrated that several GCs such as cortisol and dexamethasone (Dex) were
      frequently detected in effluents collected from Japanese sewage treatment plants
      (STPs) in 2012. In this study, we used the GC-Responsive Chemical-Activated
      LUciferase gene eXpression (GR-CALUX) assay to elucidate GC receptor (GR)
      agonistic activities of ten pure synthetic GCs and selected STP effluents in
      Japan for assessment of the risks associated with the presence of GR agonists.
      The tested GCs demonstrated dose-dependent agonistic effects in the GR-CALUX
      assay and their EC50 values were calculated for estimation of relative potencies
      (REPs) compared to Dex. The GR agonistic potency was in the rank of: clobetasol
      propionate > clobetasone butyrate > betamethasone 17-valerate > difluprednate >
      betamethasone 17,21-dipropionate > Dex > betamethasone > 6alpha
      methylprednisolone > prednisolone > cortisol. The GR agonistic activity in STP
      effluents as measured in Dex-equivalent (Dex-EQ) activities ranged from < 3.0-78
      ng L(-1) (median: 29 ng L(-1), n = 50). To evaluate the contribution of the
      target GCs, theoretical Dex-EQs were calculated by multiplying the concentrations
      of each GC by its respective REP. Our calculation of Dex-EQ contribution for
      individual GR agonists indicated that the well-known GCs cortisol and Dex should
      not be given priority for subsequent in vivo testing, monitoring and removal
      experiments, but rather the highly potent synthetic GCs clobetasol propionate and
      betamethasone 17-valerate (REP = 28 and 3.1) as well as other unidentified
      compounds are important GR agonists in STP effluents in Japan.

PMID- 25965048
TI  - Long-term assessment of ecological risk from deposition of elemental pollutants
      in the vicinity of the industrial area of Puchuncavi-Ventanas, central Chile.
AB  - The present work investigates soil pollution by elemental contaminants and
      compares ecological risk indexes related to industrial activities for the case
      study of Puchuncavi-Ventanas: a relevant industrial zone located in central
      Chile. Selected elements (As, Pb, Cd, Ni, Hg, V, Mn, Zn, Sr, Sb, Cr, Co, Cu, K,
      and Ba) were analyzed during a long-term period (yearly sampling campaigns during
      2007-2011), at 5 sampling stations representing different degrees of impact. PCA
      and cluster analysis allowed identifying a copper smelter and a coal-fired power
      plant complex as major pollution sources. Geoaccumulation index (I geo),
      enrichment factor (EF), contamination factor (Cf), contamination degree (C deg),
      and integrated pollution index (IPI) are critically discussed for quantitative
      ecological risk assessment. I geo, EF and Cf indexes are producing comparable
      environmental information, showing moderate to high pollution risks in the area
      that demands further monitoring and adoption of prevention and remediation
      measures. CAPSULE: Long term assessment of elemental pollution around an
      industrial area. New insight on ecological risk indexes for trace element
      pollution in soils, by critical comparison among them.

PMID- 25965049
TI  - Influence of pollutant build-up on variability in wash-off from urban road
      surfaces.
AB  - Variability in the pollutant wash-off process is a concept which needs to be
      understood in-depth in order to better assess the outcomes of stormwater quality
      models, and thereby strengthen stormwater pollution mitigation strategies.
      Current knowledge about the wash-off process does not extend to a clear
      understanding of the influence of the initially available pollutant build-up on
      the variability of the pollutant wash-off load and composition. Consequently,
      pollutant wash-off process variability is poorly characterised in stormwater
      quality models, which can result in inaccurate stormwater quality predictions.
      Mathematical simulation of particulate wash-off from three urban road surfaces
      confirmed that the wash-off load of particle size fractions < 150 MUm and > 150
      MUm after a storm event vary with the build-up of the respective particle size
      fractions available at the beginning of the storm event. Furthermore, pollutant
      load and composition associated with the initially available build-up of < 150
      MUm particles predominantly influence the variability in washed-off pollutant
      load and composition. The influence of the build-up of pollutants associated with
      > 150 MUm particles on wash-off process variability is significant only for
      relatively shorter duration storm events.

PMID- 25965050
TI  - An integrated assessment of two decades of air pollution policy making in Spain:
      Impacts, costs and improvements.
AB  - This paper analyses the effects of policy making for air pollution abatement in
      Spain between 2000 and 2020 under an integrated assessment approach with the
      AERIS model for number of pollutants (NOx/NO2, PM10/PM2.5, O3, SO2, NH3 and VOC).
      The analysis of the effects of air pollution focused on different aspects:
      compliance with the European limit values of Directive 2008/50/EC for NO2 and
      PM10 for the Spanish air quality management areas; the evaluation of impacts
      caused by the deposition of atmospheric sulphur and nitrogen on ecosystems; the
      exceedance of critical levels of NO2 and SO2 in forest areas; the analysis of O3
      induced crop damage for grapes, maize, potato, rice, tobacco, tomato, watermelon
      and wheat; health impacts caused by human exposure to O3 and PM2.5; and costs on
      society due to crop losses (O3), disability-related absence of work staff and
      damage to buildings and public property due to soot-related soiling (PM2.5). In
      general, air quality policy making has delivered improvements in air quality
      levels throughout Spain and has mitigated the severity of the impacts on
      ecosystems, health and vegetation in 2020 as target year. The findings of this
      work constitute an appropriate diagnosis for identifying improvement potentials
      for further mitigation for policy makers and stakeholders in Spain. 

PMID- 25965051
TI  - Application of management tools to integrate ecological principles with the
      design of marine infrastructure.
AB  - Globally the coastal zone is suffering the collateral damage from continuing
      urban development and construction, expanding resource sectors, increasing
      population, regulation to river flow, and on-going land change and degradation.
      While protection of natural coastal habitat is recommended, balancing
      conservation with human services is now the challenge for managers. Marine
      infrastructure such as seawalls, marinas and offshore platforms is increasingly
      used to support and provide services, but has primarily been designed for
      engineering purposes without consideration of the ecological consequences.
      Increasingly developments are seeking alternatives to hard engineering and a
      range of ecological solutions has begun to replace or be incorporated into marine
      and coastal infrastructure. But too often, hard engineering remains the primary
      strategy because the tools for managers to implement ecological solutions are
      either lacking or not supported by policy and stakeholders. Here we outline
      critical research needs for marine urban development and emerging strategies that
      seek to mitigate the impacts of marine infrastructure. We present case studies to
      highlight the strategic direction necessary to support management decisions
      internationally. 

PMID- 25965052
TI  - The potential use of Piptatherum miliaceum for the phytomanagement of mine
      tailings in semiarid areas: Role of soil fertility and plant competition.
AB  - Phytomanagement in terms of phytostabilisation has been proposed as a suitable
      technique to decrease the environmental risks of metal(loid) enriched mine
      tailings. Nevertheless, at these sites some issues must be solved to assure the
      long-term establishment of vegetation (e.g. salinity, low fertility, metal(loid)
      phytotoxicity, etc.) The objective of this study was to assess the effects of the
      addition of a municipal solid waste on a mine tailings soil and on the growth and
      metal(loid) accumulation of a grass plant species (Piptatherum miliaceum). In
      addition, the effects of intra-specific interactions were evaluated. A pot
      experiment was performed during 8 months, including two soil treatments: the mine
      soil and its combination with municipal solid wastes. For each treatment, pots
      without plants, pots with one plant, and pots with two plants were arranged. The
      addition of municipal solid wastes improved the soil fertility and plant growth
      in the mine soil, but also increased the mobile fractions of Zn, Pb, Cd, Mn and
      Ni. Plants in the amended treatments showed better nutritional status (higher P
      and K). Stable isotope delta(15)N was associated to the better nutritional
      status, while delta(13)C and delta(18)O indicated higher photosynthetic
      efficiency and stomatal conductance in amended treatments. Although the
      accumulation in leaves of most metal(loid)s decreased with the municipal waste
      application, the concentrations in both treatments did not exceed toxic limits
      for fodder. There was an effect of intra-specific competition in plant growth,
      probably due to lack of nutrients in the mining soil or limited pots volume in
      the treatments with municipal waste. 

PMID- 25965053
TI  - Hibiscus sabdariffa calyx palliates insulin resistance, hyperglycemia,
      dyslipidemia and oxidative rout in fructose-induced metabolic syndrome rats.
AB  - BACKGROUND: The effect of Hibiscus sabdariffa calyx extract was evaluated in high
      fructose-induced metabolic syndrome rats. Insulin resistance, hyperglycemia,
      dyslipidemia and oxidative rout were induced in rats using high-fructose diet.
      High-fructose diet-fed rats were administered 100 and 200 mg kg(-1) body weight
      of H. sabdariffa extract for 3 weeks, starting from week 7 of high-fructose diet
      treatment. RESULTS: High-fructose diet significantly (P < 0.05) increased the
      serum levels of blood glucose, insulin, total cholesterol (TC), triacylglycerol
      (TAG), low-density lipoprotein cholesterol (LDLc) and very-low-density
      lipoprotein cholesterol (VLDLc), with a concomitant reduction in high-density
      lipoprotein cholesterol (HDLc). These alterations were significantly ameliorated
      by the extract. High-fructose diet-mediated decreases in the activities of
      superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px),
      glutathione reductase (GSH-red) and glucose 6-phosphate dehydrogenase (Glc 6-PD)
      were significantly (P < 0.05) attenuated. Altered levels of reduced glutathione
      (GSH) and glutathione disulfide (GSSG) were significantly (P < 0.05) restored to
      normal. High-fructose diet-mediated increases in the concentrations of
      malondialdehyde, conjugated dienes, lipid hydroperoxides, protein carbonyl and
      percentage fragmented DNA were significantly (P < 0.05) lowered by the Hibiscus
      extract. CONCLUSION: Overall, aqueous extract of H. sabdariffa palliates insulin
      resistance, hyperglycemia, dyslipidemia and oxidative rout in high-fructose
      induced metabolic syndrome rats.

PMID- 25965054
TI  - Triply Hydrogen-Bond-Directed Enantioselective Assembly of Pyrrolobenzo-1,4
      diazine Skeletons with Quaternary Stereocenters.
AB  - Highly efficient synthesis of optically enriched pyrrolobenzo-1,4-diazines
      bearing quaternary stereocenters has been realized through the chiral Bronsted
      acid-catalyzed Pictet-Spengler reaction of 2-(1H-pyrrol-1-yl)anilines and alpha
      ketoamides in good to excellent yields and enantioselectivities. Computational
      studies suggest an unprecedented phenomenon whereby the chiral phosphoric acid
      catalyst employs attractive arene C-H???N hydrogen bonding to activate the
      substrate and induce chirality through a triple hydrogen-bonding interaction.

PMID- 25965055
TI  - Vitrectomy for idiopathic macular hole.
AB  - BACKGROUND: A macular hole is an anatomic opening in the retina that develops at
      the fovea. Macular holes can be seen in highly myopic eyes or following ocular
      trauma, but the great majority are idiopathic. Pars plana vitrectomy was
      introduced to treat full-thickness macular holes, which if left untreated have a
      poor prognosis since spontaneous closure and visual recovery are rare.Vitrectomy
      is a surgical technique involving the removal of the vitreous body that fills the
      eye. The surgeon inserts thin cannulas into the eyes through scleral incisions to
      relieve traction exerted by the vitreous or epiretinal membranes to the central
      retina and to induce glial tissue to bridge and close the hole. OBJECTIVES: The
      primary objective of this review was to examine the effects of vitrectomy for
      idiopathic macular hole on visual acuity. A secondary objective was to
      investigate anatomic effects on hole closure and other dimensions of visual
      function, as well as to report on adverse effects recorded in included studies.
      SEARCH METHODS: We searched the Cochrane Eyes and Vision Group Trials Register (4
      March 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; 2015,
      Issue 2), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations,
      Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to March 2015), EMBASE (January
      1980 to March 2015), Latin American and Caribbean Health Sciences Literature
      Database (LILACS) (January 1982 to March 2015), the Web of Science Conference
      Proceedings Citation Index-Science (CPCI-S) (January 1980 to March 2015), the
      ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov
      (www.clinicaltrials.gov) and the World Health Organization (WHO) International
      Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did
      not use any date or language restrictions in the electronic searches for trials.
      We last searched the electronic databases on 4 March 2015. SELECTION CRITERIA: We
      included randomised controlled trials comparing vitrectomy (with or without
      internal limiting membrane peeling) to no treatment (that is observation) for
      macular holes. DATA COLLECTION AND ANALYSIS: We used standard methodological
      procedures expected by Cochrane. Two review authors independently extracted the
      data. We estimated best corrected visual acuity and macular hole closure at 6 to
      12 months of follow-up. MAIN RESULTS: Three studies provided data on the
      comparison between vitrectomy and observation in eyes with macular hole and
      visual acuity less than 20/50. Two studies, conducted in the USA and published in
      1996 and 1997, used a similar protocol and included participants with stage II
      macular hole (42 eyes randomised, 36 analysed, number of participants not
      reported) or participants with stage III/IV hole (129 eyes of 120 participants,
      115 eyes in analyses). The third study, conducted in the UK and published in
      2004, included 185 eyes of 174 participants with full-thickness macular hole (41
      eyes with stage II holes and 74 eyes with stage III/IV holes in analyses).
      Studies were of good quality for randomisation and allocation concealment,
      whereas visual acuity measurement was unmasked.At 6 to 12 months, visual acuity
      was improved by about 1.5 Snellen lines (-0.16 logMAR, 95% confidence intervals 
      0.23 to -0.09 logMAR, 270 eyes, moderate-quality evidence). The chances of
      macular hole closure at 6 to 12 months were greatly increased using vitrectomy,
      yielding an odds ratio of 31.4 (95% confidence intervals 14.9 to 66.3, 265 eyes,
      high-quality evidence; raw sum data: 76% vitrectomy, 11% observation). Vitrectomy
      was beneficial both in smaller (stage II) and in larger (stage III/IV) macular
      holes.The largest study reported that cataract surgery was needed in about half
      of cases at two years after operation and that retinal detachment occurred in
      about 5% of operated eyes. AUTHORS' CONCLUSIONS: Vitrectomy is effective in
      improving visual acuity, resulting in a moderate visual gain, and in achieving
      hole closure in people with macular hole. However, these results may not apply to
      modern surgery due to technological improvements in vitrectomy techniques.

PMID- 25965056
TI  - Ultrarapid and ultrasensitive electrical detection of proteins in a three
      dimensional biosensor with high capture efficiency.
AB  - The realization of a high-throughput biosensor platform with ultrarapid detection
      of biomolecular interactions and an ultralow limit of detection in the femtomolar
      (fM) range or below has been retarded due to sluggish binding kinetics caused by
      the scarcity of probe molecules on the nanostructures and/or limited mass
      transport. Here, as a new method for the highly efficient capture of biomolecules
      at extremely low concentration, we tested a three-dimensional (3D) platform of a
      bioelectronic field-effect transistor (bio-FET) with vertically aligned and
      highly dense one-dimensional (1D) ZnO nanorods (NRs) as a sensing surface capped
      by an ultrathin TiO2 layer for improved electrolytic stability on a chemical
      vapor-deposited graphene (Gr) channel. The ultrarapid detection capability with a
      very fast response time (~1 min) at the fM level of proteins in the proposed 3D
      bio-FET is primarily attributed to the fast binding kinetics of the probe-target
      proteins due to the small diffusion length of the target molecules to reach the
      sensor surface and the substantial number of probe molecules available on the
      largely increased surface area of the vertical ZnO NRs. This new 3D electrical
      biosensor platform can be easily extended to other electrochemical nanobiosensors
      and has great potential for practical applications in miniaturized biosensor
      integrated systems. 

PMID- 25965058
TI  - On the state of scientific English and how to improve it--Part 8: Where "because"
      should be used instead of "as" and "since".

PMID- 25965059
TI  - Phylogenetic path analysis reveals the importance of niche-related biological
      traits on geographic range size in mammals.

PMID- 25965057
TI  - Walking and Walkability: Is Wayfinding a Missing Link? Implications for Public
      Health Practice.
AB  - BACKGROUND: Research on walking and walkability has yet to focus on wayfinding,
      the interactive, problem-solving process by which people use environmental
      information to locate themselves and navigate through various settings. METHODS:
      We reviewed the literature on outdoor pedestrian-oriented wayfinding to examine
      its relationship to walking and walkability, 2 areas of importance to physical
      activity promotion. RESULTS: Our findings document that wayfinding is cognitively
      demanding and can compete with other functions, including walking itself.
      Moreover, features of the environment can either facilitate or impede wayfinding,
      just as environmental features can influence walking. CONCLUSIONS: Although there
      is still much to be learned about wayfinding and walking behaviors, our review
      helps frame the issues and lays out the importance of this area of research and
      practice.

PMID- 25965060
TI  - Urinary bladder paraganglioma presenting as micturition-induced palpitations,
      dyspnea, and angina.
AB  - BACKGROUND: Sympathetic urinary bladder paragangliomas are rare catecholamine
      secreting neuroendocrine tumors arising from neural crest cells. They are
      uncommon urinary bladder neoplasms. Symptoms classically include micturition
      related or unrelated palpitations and syncope with hypertension, headaches,
      diaphoresis, and hematuria. Other than being attributable to vasovagal reactions,
      micturition-induced cardiovascular symptoms should prompt a search for
      catecholamine-secreting tumors such as a urinary bladder paraganglioma, as in
      this case. CASE REPORT: A 45-year-old asthmatic African-American female presented
      with episodic hematuria that began 4 years ago and episodes of micturition
      induced palpitations, dyspnea, substernal tightness, sweating, and throbbing
      headaches. Computed tomography with contrast revealed an enhancing mass along the
      anterior urinary bladder wall, measuring 2.4*3.5 cm. On Positron emission
      Tomography with [18F] fluorodeoxyglucose integrated with computed tomography (18F
      FDG PET/CT), the urinary bladder mass was 18F-FDG avid. Serum normetanephrine and
      supine plasma norepinephrine were significantly elevated and there was mild
      elevation of supine plasma epinephrine. Transurethral resection of the bladder
      mass revealed a neoplasm with microscopic features and immunohistochemical
      profile positive for synaptophysin and chromogranin, with negative screening
      cytokeratin AE1/AE3, suggesting a paraganglioma. Following resection of the
      paraganglioma, there was complete resolution of micturition-induced
      cardiovascular symptoms on long-term follow-up. CONCLUSIONS: Micturition-related
      cardiovascular symptoms are commonly attributed to vasovagal reactions. However,
      urinary bladder pathologies must be ruled out as a cause, as in this rare case of
      a urinary bladder paraganglioma exhibiting catecholaminergic symptoms.

PMID- 25965062
TI  - Correction: Schip1 Is a Novel Podocyte Foot Process Protein that Mediates Actin
      Cytoskeleton Rearrangements and Forms a Complex with Nherf2 and Ezrin.

PMID- 25965061
TI  - Characterization of Mutants of Human Small Heat Shock Protein HspB1 Carrying
      Replacements in the N-Terminal Domain and Associated with Hereditary Motor Neuron
      Diseases.
AB  - Physico-chemical properties of the mutations G34R, P39L and E41K in the N
      terminal domain of human heat shock protein B1 (HspB1), which have been
      associated with hereditary motor neuron neuropathy, were analyzed. Heat-induced
      aggregation of all mutants started at lower temperatures than for the wild type
      protein. All mutations decreased susceptibility of the N- and C-terminal parts of
      HspB1 to chymotrypsinolysis. All mutants formed stable homooligomers with a
      slightly larger apparent molecular weight compared to the wild type protein. All
      mutations analyzed decreased or completely prevented phosphorylation-induced
      dissociation of HspB1 oligomers. When mixed with HspB6 and heated, all mutants
      yielded heterooligomers with apparent molecular weights close to ~400 kDa.
      Finally, the three HspB1 mutants possessed lower chaperone-like activity towards
      model substrates (lysozyme, malate dehydrogenase and insulin) compared to the
      wild type protein, conversely the environmental probe bis-ANS yielded higher
      fluorescence with the mutants than with the wild type protein. Thus, in vitro the
      analyzed N-terminal mutations increase stability of large HspB1 homooligomers,
      prevent their phosphorylation-dependent dissociation, modulate their interaction
      with HspB6 and decrease their chaperoning capacity, preventing normal functioning
      of HspB1. 

PMID- 25965063
TI  - Being Small for Gestational Age: Does it Matter for the Neurodevelopment of
      Premature Infants? A Cohort Study.
AB  - BACKGROUND: Whether being small for gestational age (SGA) increases the risk of
      adverse neurodevelopmental outcome in premature infants remains controversial.
      OBJECTIVE: to study the impact of SGA (birthweight < percentile 10) on cognition,
      behavior, neurodevelopmental impairment and use of therapy at 5 years old.
      METHODS: This population-based prospective cohort included infants born before 32
      weeks of gestation. Cognition was evaluated with the K-ABC, and behavior with the
      Strengths and Difficulties Questionnaire (SDQ). Primary outcomes were cognitive
      and behavioral scores, as well as neurodevelopmental impairment (cognitive score
      < 2SD, hearing loss, blindness, or cerebral palsy). The need of therapy, an
      indirect indicator of neurodevelopmental impairment, was a secondary outcome.
      Linear and logistic regression models were used to analyze the association of SGA
      with neurodevelopment. RESULTS: 342/515 (76%) premature infants were assessed.
      SGA was significantly associated with hyperactivity scores of the SDQ
      (coefficient 0.81, p < 0.04), but not with cognitive scores, neurodevelopmental
      impairment or the need of therapy. Gestational age, socio-economic status, and
      major brain lesions were associated with cognitive outcome in the univariate and
      multivariate model, whereas asphyxia, sepsis and bronchopulmonary dysplasia were
      associated in the univariate model only. Severe impairment was associated with
      fetal tobacco exposition, asphyxia, gestational age and major brain lesions.
      Different neonatal factors were associated with the use of single or multiple
      therapies: children with one therapy were more likely to have suffered birth
      asphyxia or necrotizing enterocolitis, whereas the need for several therapies was
      predicted by major brain lesions. DISCUSSION: In this large cohort of premature
      infants, assessed at 5 years old with a complete panel of tests, SGA was
      associated with hyperactive behavior, but not with cognition, neurodevelopmental
      impairment or use of therapy. Birthweight <10th percentile alone does not appear
      to be an independent risk factor of neurodevelopmental adverse outcome in preterm
      children.

PMID- 25965064
TI  - African migrant patients' trust in Chinese physicians: a social ecological
      approach to understanding patient-physician trust.
AB  - BACKGROUND: Patient trust in physicians is a critical determinant of health
      seeking behaviors, medication adherence, and health outcomes. A crisis of
      interpersonal trust exists in China, extending throughout multiple social
      spheres, including the healthcare system. At the same time, with increased
      migration from Africa to China in the last two decades, Chinese physicians must
      establish mutual trust with an increasingly diverse patient population. We
      undertook a qualitative study to identify factors affecting African migrants'
      trust in Chinese physicians and to identify potential mechanisms for promoting
      trust. METHODS/PRINCIPAL FINDINGS: We conducted semi-structured, in-depth
      interviews with 40 African migrants in Guangzhou, China. A modified version of
      the social ecological model was used as a theoretical framework. At the patient
      physician level, interpersonal treatment, technical competence, perceived
      commitment and motive, and language concordance were associated with enhanced
      trust. At the health system level, two primary factors influenced African
      migrants' trust in their physicians: the fee-for-service payment system and lack
      of continuity with any one physician. Patients' social networks and the broader
      socio-cultural context of interactions between African migrants and Chinese
      locals also influenced patients' trust of their physicians. CONCLUSIONS: These
      findings demonstrate the importance of factors beyond the immediate patient
      physician interaction and suggest opportunities to promote trust through health
      system interventions.

PMID- 25965065
TI  - Not Just a Sum? Identifying Different Types of Interplay between Constituents in
      Combined Interventions.
AB  - MOTIVATION: Experiments in which the effect of combined manipulations is compared
      with the effects of their pure constituents have received a great deal of
      attention. Examples include the study of combination therapies and the comparison
      of double and single knockout model organisms. Often the effect of the combined
      manipulation is not a mere addition of the effects of its constituents, with
      quite different forms of interplay between the constituents being possible. Yet,
      a well-formalized taxonomy of possible forms of interplay is lacking, let alone a
      statistical methodology to test for their presence in empirical data. RESULTS:
      Starting from a taxonomy of a broad range of forms of interplay between
      constituents of a combined manipulation, we propose a sound statistical
      hypothesis testing framework to test for the presence of each particular form of
      interplay. We illustrate the framework with analyses of public gene expression
      data on the combined treatment of dendritic cells with curdlan and GM-CSF and
      show that these lead to valuable insights into the mode of action of the
      constituent treatments and their combination. AVAILABILITY AND IMPLEMENTATION: R
      code implementing the statistical testing procedure for microarray gene
      expression data is available as supplementary material. The data are available
      from the Gene Expression Omnibus with accession number GSE32986.

PMID- 25965066
TI  - In Silico and In Vitro Analysis of Bacoside A Aglycones and Its Derivatives as
      the Constituents Responsible for the Cognitive Effects of Bacopa monnieri.
AB  - Bacopa monnieri has been used in Ayurvedic medicine to improve memory and
      cognition. The active constituent responsible for its pharmacological effects is
      bacoside A, a mixture of dammarane-type triterpenoid saponins containing sugar
      chains linked to a steroid aglycone skeleton. Triterpenoid saponins have been
      reported to be transformed in vivo to metabolites that give better biological
      activity and pharmacokinetic characteristics. Thus, the activities of the parent
      compounds (bacosides), aglycones (jujubogenin and pseudojujubogenin) and their
      derivatives (ebelin lactone and bacogenin A1) were compared using a combination
      of in silico and in vitro screening methods. The compounds were docked into 5
      HT1A, 5-HT2A, D1, D2, M1 receptors and acetylcholinesterase (AChE) using AutoDock
      and their central nervous system (CNS) drug-like properties were determined using
      Discovery Studio molecular properties and ADMET descriptors. The compounds were
      screened in vitro using radioligand receptor binding and AChE inhibition assays.
      In silico studies showed that the parent bacosides were not able to dock into the
      chosen CNS targets and had poor molecular properties as a CNS drug. In contrast,
      the aglycones and their derivatives showed better binding affinity and good CNS
      drug-like properties, were well absorbed through the intestines and had good
      blood brain barrier (BBB) penetration. Among the compounds tested in vitro,
      ebelin lactone showed binding affinity towards M1 (Ki = 0.45 MUM) and 5-HT2A
      (4.21 MUM) receptors. Bacoside A and bacopaside X (9.06 MUM) showed binding
      affinity towards the D1 receptor. None of the compounds showed any inhibitory
      activity against AChE. Since the stimulation of M1 and 5-HT2A receptors has been
      implicated in memory and cognition and ebelin lactone was shown to have the
      strongest binding energy, highest BBB penetration and binding affinity towards M1
      and 5-HT2A receptors, we suggest that B. monnieri constituents may be transformed
      in vivo to the active form before exerting their pharmacological activity. 

PMID- 25965067
TI  - In vitro recapitulation of functional microvessels for the study of endothelial
      shear response, nitric oxide and [Ca2+]i.
AB  - Microfluidic technologies enable in vitro studies to closely simulate in vivo
      microvessel environment with complexity. Such method overcomes certain constrains
      of the statically cultured endothelial monolayers and enables the cells grow
      under physiological range of shear flow with geometry similar to microvessels in
      vivo. However, there are still existing knowledge gaps and lack of convincing
      evidence to demonstrate and quantify key biological features of the microfluidic
      microvessels. In this paper, using advanced micromanufacturing and microfluidic
      technologies, we presented an engineered microvessel model that mimicked the
      dimensions and network structures of in vivo microvessels with a long-term and
      continuous perfusion capability, as well as high-resolution and real-time imaging
      capability. Through direct comparisons with studies conducted in intact
      microvessels, our results demonstrated that the cultured microvessels formed
      under perfused conditions recapitulated certain key features of the microvessels
      in vivo. In particular, primary human umbilical vein endothelial cells were
      successfully cultured the entire inner surfaces of the microchannel network with
      well-developed junctions indicated by VE-cadherin staining. The morphological and
      proliferative responses of endothelial cells to shear stresses were quantified
      under different flow conditions which was simulated with three-dimensional shear
      dependent numerical flow model. Furthermore, we successfully measured agonist
      induced changes in intracellular Ca2+ concentration and nitric oxide production
      at individual endothelial cell levels using fluorescence imaging. The results
      were comparable to those derived from individually perfused intact venules. With
      in vivo validation of its functionalities, our microfluidic model demonstrates a
      great potential for biological applications and bridges the gaps between in vitro
      and in vivo microvascular research. 

PMID- 25965068
TI  - Understanding brains: details, intuition, and big data.
AB  - Understanding how the brain works requires a delicate balance between the
      appreciation of the importance of a multitude of biological details and the
      ability to see beyond those details to general principles. As technological
      innovations vastly increase the amount of data we collect, the importance of
      intuition into how to analyze and treat these data may, paradoxically, become
      more important. 

PMID- 25965069
TI  - Serological evidence of influenza A viruses in frugivorous bats from Africa.
AB  - Bats are likely natural hosts for a range of zoonotic viruses such as Marburg,
      Ebola, Rabies, as well as for various Corona- and Paramyxoviruses. In 2009/10,
      researchers discovered RNA of two novel influenza virus subtypes--H17N10 and
      H18N11--in Central and South American fruit bats. The identification of bats as
      possible additional reservoir for influenza A viruses raises questions about the
      role of this mammalian taxon in influenza A virus ecology and possible public
      health relevance. As molecular testing can be limited by a short time window in
      which the virus is present, serological testing provides information about past
      infections and virus spread in populations after the virus has been cleared. This
      study aimed at screening available sera from 100 free-ranging, frugivorous bats
      (Eidolon helvum) sampled in 2009/10 in Ghana, for the presence of antibodies
      against the complete panel of influenza A haemagglutinin (HA) types ranging from
      H1 to H18 by means of a protein microarray platform. This technique enables
      simultaneous serological testing against multiple recombinant HA-types in 5 MUl
      of serum. Preliminary results indicate serological evidence against avian
      influenza subtype H9 in about 30% of the animals screened, with low-level cross
      reactivity to phylogenetically closely related subtypes H8 and H12. To our
      knowledge, this is the first report of serological evidence of influenza A
      viruses other than H17 and H18 in bats. As avian influenza subtype H9 is
      associated with human infections, the implications of our findings from a public
      health context remain to be investigated.

PMID- 25965071
TI  - Synthesis and reactivity of a zwitterionic palladium allyl complex supported by a
      perchlorinated carboranyl phosphine.
AB  - A zwitterionic palladium complex of a phosphine bearing a perchlorinated carba
      closo-dodecaborate anion as a ligand substituent is reported. A single-crystal X
      ray diffraction study reveals that, in the solid state, one of the chlorides of
      the carborane cage occupies a coordination site of the square-planar complex.
      However, in solution, the P-carborane bond of the ligand is rapidly rotating at
      temperatures as low as -90  degrees C, which demonstrates the carborane
      substituent's weak coordinative ability even though this anion is covalently
      linked to the phosphine ligand. The complex is thermally stable and catalyzes the
      vinyl addition polymerization of norbornene. 

PMID- 25965070
TI  - Pathways and networks-based analysis of candidate genes associated with nicotine
      addiction.
AB  - Nicotine is the addictive substance in tobacco and it has a broad impact on both
      the central and peripheral nervous systems. Over the past decades, an increasing
      number of genes potentially involved in nicotine addiction have been identified
      by different technical approaches. However, the molecular mechanisms underlying
      nicotine addiction remain largely unclear. Under such situation, a comprehensive
      analysis focusing on the overall functional characteristics of these genes, as
      well as how they interact with each other will provide us valuable information to
      understand nicotine addiction. In this study, we presented a systematic analysis
      on nicotine addiction-related genes to identify the major underlying biological
      themes. Functional analysis revealed that biological processes and biochemical
      pathways related to neurodevelopment, immune system and metabolism were
      significantly enriched in the nicotine addiction-related genes. By extracting the
      nicotine addiction-specific subnetwork, a number of novel genes associated with
      addiction were identified. Moreover, we constructed a schematic molecular network
      for nicotine addiction via integrating the pathways and network, providing an
      intuitional view to understand the development of nicotine addiction. Pathway and
      network analysis indicated that the biological processes related to nicotine
      addiction were complex. Results from our work may have important implications for
      understanding the molecular mechanism underlying nicotine addiction. 

PMID- 25965072
TI  - How to confirm and exclude different models of material properties in the Casimir
      effect.
AB  - We formulate a method allowing us to confirm or exclude the alternative models of
      material properties at some definite confidence level in experiments on measuring
      the Casimir force. The method is based on the consideration of differences
      between the theoretical and mean measured quantities and the confidence intervals
      for these differences found at sufficiently high or low confidence probabilities.
      The developed method is applied to the data of four recent experiments on
      measuring the gradient of the Casimir force by means of a dynamic atomic force
      microscope. It is shown that in experiments with Au-Au and Ni-Ni test bodies,
      where the Drude model approach is excluded at a 95% confidence level, the plasma
      model approach agrees with the data at higher than 90% confidence. In experiments
      using an Au sphere interacting with either a Ni plate or a graphene-coated
      substrate, the measurement data agree with the common prediction of the Drude and
      plasma model approaches and theory using the polarization tensor at 90% and 80%
      confidence levels, respectively. 

PMID- 25965073
TI  - Mesosponge Optical Sinks for Multifunctional Mercury Ion Assessment and Recovery
      from Water Sources.
AB  - Using the newly developed organic-inorganic colorant membrane is an attractive
      approach for the optical detection, selective screening and removal, and waste
      management recovery of highly toxic elements, such as Hg(II) ions, from water
      sources. In the systematic mesosponge optical sinks (MOSs), anchoring organic
      colorants into 3D, well-defined cage cavities and interconnected tubular pores
      (10 nm) in the long microscale channels of membrane scaffolds enhances the
      requirements and intrinsic properties of the hierarchal membrane. This scalable
      design is the first to allow control of the multifunctional processes of a
      membrane in a one-step screening procedure, such as the detection/recognition,
      removal, and filtration of ultratrace Hg(II) ions, even from actual water sources
      (i.e., tap, underground). The selective recovery, detection, and extraction
      processes of Hg(II) ions in a heterogeneous mixture with inorganic cations and
      anions as well as organic molecules and surfactants are mainly dependent on the
      structure of the colorant agent, the pH conditions, competitive ion-system
      compositions and concentrations, and Hg-to-colorant binding events. Our result
      shows that the solid MOS membrane arrays can be repeatedly recycled and retain
      their hierarchal mesosponge sink character, avoiding fouling via the
      precipitation of metal salts as a result of the reuse cycle. The Hg(II) ion
      rejection and the permeation of nonselective elements based on the membrane
      filtration protocol may be key considerations in water purification and
      separation requirements. The selective recovery process of Hg(II) ions in actual
      contaminated samples collected from tap and underground water sources in Saudi
      Arabia indicates the practical feasibility of our designed MOS membrane arrays. 

PMID- 25965074
TI  - Palladium-catalyzed C-H ethoxycarbonyldifluoromethylation of electron-rich
      heteroarenes.
AB  - The first Pd-catalyzed C-H ethoxycarbonyldifluoromethylation with BrCF2CO2Et has
      been developed. The use of a bidentate phosphine ligand (Xantphos) is critical
      for the reaction to occur. A variety of electron-rich heteroarenes, including
      indoles, furans, thiophenes, and pyrroles, can be
      ethoxycarbonyldifluoromethylated in moderate to excellent yields. The reactions
      take place at the C-H bonds adjacent to the heteroatoms with high
      regioselectivity. This method provides a new protocol for the introduction of
      difuoroalkyl groups into electron-rich heteroarenes. 

PMID- 25965075
TI  - Probing of Competitive Displacement Adsorption of Casein at Oil-in-Water
      Interface Using Equilibrium Force Distance Measurements.
AB  - The equilibrium force distance measurement is employed for the first time to
      probe the competitive and displacement adsorption of casein at an oil-water (O/W)
      emulsion interface that was initially adsorbed with either a diblock polymer or
      an anionic surfactant. A significant change in the force-distance profile was
      observed under the competitive displacement adsorption of casein, which is
      further confirmed from the hydrodynamic diameter and zeta potential measurements.
      A decrease in the onset of repulsion and decay length are observed on competitive
      adsorption of smaller size casein molecules at O/W interface. With addition of
      casein in PVA-vac diblock polymer stabilized emulsion, the onset of repulsion
      decreases from 88 to 48 nm whereas the magnitude of force increases from 1 to 19
      nN. The force decay length is reduced from 10.5 to 4.5 nm upon addition of
      casein. Our results suggest the complete replacement of adsorbed diblock polymers
      by casein molecules. The hydrodynamic diameter and zeta potential measurements
      corroborate the casein mediated polymer displacement and the competitive
      adsorption of casein at the O/W interface. In the case of anionic surfactant
      covered O/W interfaces, casein molecules weakly associate at the interface
      without displacing the smaller size surfactant molecules where no significant
      changes in the onset repulsion and force profiles are observed. These results
      suggest that the casein molecules are effective displacers for replacement of
      adsorbed macromolecules from formulations, which has several important practical
      applications. 

PMID- 25965076
TI  - Reactivity of oxygen deficient cerium oxide clusters with small gaseous
      molecules.
AB  - Oxygen deficient cerium oxide cluster ions, Ce(n)O(m)(+) (n = 2-10, m = 1-2n)
      were prepared in the gas phase by laser ablation of a cerium oxide rod. The
      reactivity of the cluster ions was investigated using mass spectrometry, finding
      that oxygen deficient clusters are able to extract oxygen atoms from CO, CO2, NO,
      N2O, and O2 in the gas phase. The oxygen transfer reaction is explained in terms
      of the energy balance between the bond dissociation energy of an oxygen
      containing molecule and the oxygen affinity of the oxygen-deficient cerium oxide
      clusters, which is supported by DFT calculations. The reverse reaction, i.e.,
      formation of the oxygen deficient cluster ions from the stoichiometric ones was
      also examined. It was found that intensive heating of the stoichiometric clusters
      results in formation of oxygen deficient clusters via Ce(n)O(2n)(+) -> Ce(n)O(2n
      2)(+) + O2, which was found to occur at different temperatures depending on
      cluster size, n.

PMID- 25965077
TI  - Electrochemical Genosensor To Detect Pathogenic Bacteria (Escherichia coli
      O157:H7) As Applied in Real Food Samples (Fresh Beef) To Improve Food Safety and
      Quality Control.
AB  - The electrochemical genosensor is one of the most promising methods for the rapid
      and reliable detection of pathogenic bacteria. In a previous work, we performed
      an efficient electrochemical genosensor detection of Staphylococcus aureus by
      using lead sulfide nanoparticles (PbSNPs). As a continuation of this study, in
      the present work, the electrochemical genosensor was used to detect Escherichia
      coli O157:H7. The primer and probes were designed using NCBI database and Sigma
      Aldrich primer and probe software. The capture and signalizing probes were
      modified by thiol (SH) and amine (NH2), respectively. Then, the signalizing probe
      was connected using cadmium sulfide nanoparticles (CdSNPs), which showed well
      defined peaks after electrochemical detection. The genosensor was prepared by
      immobilization of complementary DNA on the gold electrode surface, which
      hybridizes with a specific fragment gene from pathogenic to make a sandwich
      structure. The conductivity and sensitivity of the sensor were increased by using
      multiwalled carbon nanotubes (MWCNT) that had been modified using chitosan
      deposited as a thin layer on the glass carbon electrode (GCE) surface, followed
      by a deposit of bismuth. The peak currents of E. coli O157:H7 correlated in a
      linear fashion with the concentration of tDNA. The detection limit was 1.97 * 10(
      14) M, and the correlation coefficient was 0.989. A poorly defined current
      response was observed as the negative control and baseline. Our results showed
      high sensitivity and selectivity of the electrochemical DNA biosensor to the
      pathogenic bacteria E. coli O157:H7. The biosensor was also used to evaluate the
      detection of pathogen in real beef samples contaminated artificially. Compared
      with other electrochemical DNA biosensors, we conclude that this genosensor
      provides for very efficient detection of pathogenic bacteria. Therefore, this
      method may have potential application in food safety and related fields. 

PMID- 25965078
TI  - Herbal diuretics in medieval Persian and Arabic medicine.
AB  - OBJECTIVE: In accord with the notions of humoralism that prevailed in medieval
      medicine, therapeutic interventions, including diuretics, were used to restore
      the disturbed balance among the four humors of the human body: blood, phlegm,
      yellow bile, and black bile. Most diuretics were derived from plants. The primary
      textual reference on herbal diuretics was Dioscorides's De Materia Medica, which
      was written during the first century CE. DESIGN: The authors reviewed the
      medieval medical texts written in Persian and Arabic and compiled a list of 135
      herbal diuretics used by the medieval medical authorities for treating various
      ailments. RESULTS: Between the 8th and 11th centuries CE, Middle Eastern
      physicians systematically reviewed extant books on medicine and pharmacotherapy
      and compiled new and expanded lists of herbal medicines, diuretics in particular.
      Furthermore, they introduced new chemical methods of extraction, distillation,
      and compounding in the use of herbal medicines. CONCLUSIONS: Several herbal
      remedies now are considered as potentially safe and affordable alternatives to
      chemical pharmaceuticals. Thus, research on medieval herbal therapies may prove
      to be relevant to the practice of current cardiovascular and renal
      pharmacotherapy. The authors propose that modern research methods can be employed
      to determine which of these agents actually are effective as diuretics.

PMID- 25965079
TI  - State-level spending on health care and social services for people living with
      HIV/AIDS in the USA: a systematic review.
AB  - Every year for the past decade, approximately 50,000 people have been diagnosed
      with HIV or AIDS in the USA, and the incidence of HIV/AIDS varies considerably
      from state to state. Studies have shown that health care services, most notably
      treatment with combination antiretroviral therapy, can help people living with
      HIV/AIDS (PLWHA) live healthier, longer lives, and prevent the spread of HIV from
      person to person. In addition, social services, such as housing support and
      provision of meals, have also shown to be important for helping PLWHA adhere to
      antiretroviral treatment and maintain contact with health care providers for
      improved health outcomes. Although spending on health care and social services
      for PLWHA varies across the USA, the relationship between state-level spending on
      these services and HIV/AIDS-related outcomes is not clear. We therefore conducted
      a systematic review of peer-reviewed literature to identify studies that explore
      state-level spending on health care services and/or social services for PLWHA and
      HIV/AIDS-related health outcomes in the USA. 

PMID- 25965080
TI  - Lactobionic and cellobionic acid production profiles of the resting cells of
      acetic acid bacteria.
AB  - Lactobionic acid was produced by acetic acid bacteria to oxidize lactose.
      Gluconobacter spp. and Gluconacetobacter spp. showed higher lactose-oxidizing
      activities than Acetobacter spp. Gluconobacter frateurii NBRC3285 produced the
      highest amount of lactobionic acid per cell, among the strains tested. This
      bacterium assimilated neither lactose nor lactobionic acid. At high lactose
      concentration (30%), resting cells of the bacterium showed sufficient oxidizing
      activity for efficient production of lactobionic acid. These properties may
      contribute to industrial production of lactobionic acid by the bacterium. The
      bacterium showed higher oxidizing activity on cellobiose than that on lactose and
      produced cellobionic acid. 

PMID- 25965081
TI  - "It has been a long journey from first knowing": narratives of unplanned
      pregnancy.
AB  - Unplanned pregnancies come with risks of various health and financial
      consequences for women. Understanding such experiences is vital to aiding women
      in this health context; however, there is little research in this vein,
      particularly for college-aged young women. Narratives of unplanned pregnancy may
      help to shed light on the experiences of these women, leading to greater
      understanding and more congruent and helpful support communication, prevention,
      and education resources. The present study aimed to identify themes in unplanned
      pregnancy narratives. Stories for women who had continued their pregnancies
      differed from those of women who did not continue their pregnancies, and overall,
      narratives seemed to work toward positively reappraising and making sense of the
      experience, especially in terms of autonomy, as well as seeking affirmation and
      support for decisions made. Implications of these results will be discussed in
      terms of future narrative work in the unplanned pregnancy context. 

PMID- 25965082
TI  - Radioiodine-Associated Exacerbation of Graves' Orbitopathy in the Japanese
      Population: Randomized Prospective Study.
AB  - CONTEXT: Exacerbation of Graves' orbitopathy (GO) after radioiodine (RAI) therapy
      has been examined in some populations but has not been fully described in
      Japanese populations. OBJECTIVE: The purpose of this study was to clarify the
      characteristics of GO exacerbation after RAI therapy and the effectiveness of low
      dose prophylactic corticosteroid (PCS). DESIGN AND SETTING: This was a
      prospective randomized study in Tokyo, Japan. PATIENTS: Between June 2011 and
      June 2012, 295 patients with Graves' disease with either inactive GO or no GO
      received RAI therapy. Of these, 147 received no PCS (PCS-Off group), whereas 148
      received low-dose PCS (starting dose, 15 mg/day of prednisolone) for 6 weeks (PCS
      On group). We used magnetic resonance imaging to thoroughly evaluate GO before
      and 1 year after RAI therapy. MAIN OUTCOME MEASURES: Outcomes of GO 1 year after
      RAI therapy were determined. RESULTS: GO exacerbation occurred in 29 patients
      (9.8%), and only 7 patients (2.4%) required ophthalmic treatment. No significant
      difference in the frequency of GO exacerbation was seen between the groups (PCS
      On group: n = 18 [12.1%]; PCS-Off group: n = 11 [7.5%]; P = .17). Significant
      prognostic factors were identified as thyroid-stimulating antibody (by 100%
      linear increase: risk ratio, 1.15; 95% confidence interval, 1.07-1.24; P = .0003)
      and clinical activity score (>=1 vs 0: risk ratio, 6.40; 95% confidence interval,
      2.17-19.7; P = .0009). CONCLUSION: Exacerbation of GO after RAI therapy in the
      Japanese population appears less common than in other populations. Low-dose PCS
      did not produce a significant preventive effect and appeared insufficient.
      Patients presenting with risk factors would thus be recommended to receive higher
      dose PCS.

PMID- 25965084
TI  - Electrochemical properties of novel titania nanostructures.
AB  - In this study, the supercapacitive properties of six new TiO2 nanostructures
      including nanodishes, three-layer nanosheets, ancient Chinese coins, single-layer
      nanosheets, hollow nanocubes, and commercial rutile TiO2 are investigated mainly
      by cyclic voltammetry, chronopotentiometry, and electrochemical impedance
      spectroscopy. The results show that among them, the TiO2 nanodishes have the
      highest discharging capacitance at 1792 mFg(-1), which is 6.4 and 1.5 times
      higher than that of TiO2 single-layer nanosheets and commercial rutile TiO2,
      respectively. We found that the electrochemical properties of the TiO2 samples
      are predominated primarily by the high-energy facets exposed, instead of by the
      Brunauer-Emmett-Teller area. An important and previously unknown finding of our
      work is that the electrochemical properties of electrode materials can be
      improved by controlling the high-energy facets. 

PMID- 25965085
TI  - BJP is linking its articles to the IUPHAR/BPS Guide to PHARMACOLOGY.
AB  - LINKED EDITORIALS: This Editorial is part of a series. To view the other
      Editorials in this series, visit:
      http://onlinelibrary.wiley.com/doi/10.1111/bph.12956/abstract;
      http://onlinelibrary.wiley.com/doi/10.1111/bph.12954/abstract;
      http://onlinelibrary.wiley.com/doi/10.1111/bph.12955/abstract and
      http://onlinelibrary.wiley.com/doi/10.1111/bph.12856/abstract. VIDEO: To view the
      video on the IUPHAR/BPS Guide to PHARMACOLOGY, visit:
      https://www.youtube.com/watch?v=Qhy3q33VtRI.

PMID- 25965083
TI  - Molecular Testing for miRNA, mRNA, and DNA on Fine-Needle Aspiration Improves the
      Preoperative Diagnosis of Thyroid Nodules With Indeterminate Cytology.
AB  - CONTEXT: Molecular testing for oncogenic mutations or gene expression in fine
      needle aspirations (FNAs) from thyroid nodules with indeterminate cytology
      identifies a subset of benign or malignant lesions with high predictive value.
      OBJECTIVE: This study aimed to evaluate a novel diagnostic algorithm combining
      mutation detection and miRNA expression to improve the diagnostic yield of
      molecular cytology. SETTING: Surgical specimens and preoperative FNAs (n = 638)
      were tested for 17 validated gene alterations using the miRInform Thyroid test
      and with a 10-miRNA gene expression classifier generating positive (malignant) or
      negative (benign) results. DESIGN: Cross-sectional sampling of thyroid nodules
      with atypia of undetermined significance/follicular lesion of undetermined
      significance (AUS/FLUS) or follicular neoplasm/suspicious for a follicular
      neoplasm (FN/SFN) cytology (n = 109) was conducted at 12 endocrinology centers
      across the United States. Qualitative molecular results were compared with
      surgical histopathology to determine diagnostic performance and model clinical
      effect. RESULTS: Mutations were detected in 69% of nodules with malignant
      outcome. Among mutation-negative specimens, miRNA testing correctly identified
      64% of malignant cases and 98% of benign cases. The diagnostic sensitivity and
      specificity of the combined algorithm was 89% (95% confidence interval [CI], 73
      97%) and 85% (95% CI, 75-92%), respectively. At 32% cancer prevalence, 61% of the
      molecular results were benign with a negative predictive value of 94% (95% CI, 85
      98%). Independently of variations in cancer prevalence, the test increased the
      yield of true benign results by 65% relative to mRNA-based gene expression
      classification and decreased the rate of avoidable diagnostic surgeries by 69%.
      CONCLUSIONS: Multiplatform testing for DNA, mRNA, and miRNA can accurately
      classify benign and malignant thyroid nodules, increase the diagnostic yield of
      molecular cytology, and further improve the preoperative risk-based management of
      benign nodules with AUS/FLUS or FN/SFN cytology.

PMID- 25965086
TI  - Age-related effects of chronic hantavirus infection on female host fecundity.
AB  - 1. Pathogens often cause detrimental effects to their hosts and, consequently,
      may influence host population dynamics that may, in turn, feed back to pathogen
      transmission dynamics. Understanding fitness effects of pathogens upon animal
      host populations can help to predict the risks that zoonotic pathogens pose to
      humans. 2. Here we determine whether chronic infection by Puumala hantavirus
      (PUUV) affects important fitness-related traits, namely the probability of
      breeding, reproductive effort and mother and offspring condition, in the bank
      vole (Myodes glareolus). Using 9 years empirical data in a PUUV endemic area in
      Central Finland, we found differences between reproductive characteristics of
      PUUV-infected and uninfected female bank voles. 3. Young infected females had a
      significantly higher, and old individuals lower, likelihood of reproducing than
      uninfected animals during the middle of the breeding season. The implication is
      that PUUV infection may have long-term deleterious effects that are observed at
      old age, while in young individuals, the infection may enhance breeding
      probability by directing resources towards current breeding. 4. Moreover, PUUV
      infection was related with the mother's body condition. Infected mothers were in
      poorer condition than uninfected mothers in the early breeding season, but were
      in better condition than uninfected mothers during the middle of the breeding
      season. Offspring body condition was positively associated with mother's body
      condition, which, in turn, was related to the PUUV infection status of the
      mother. 5. Our findings indicate that chronic infection may affect the
      reproduction of female hosts, but the effect is dependent on the host age. The
      effect of chronic hantavirus infection was small and density-independent and
      hence unlikely to contribute to the cyclic population dynamics of the host.
      However, the effects on a female's reproductive output might affect the abundance
      of young susceptible individuals in the population and hence influence the
      transmission and persistence of the pathogen. Although experimental and long-term
      capture-mark-recapture studies are required to further clarify the fitness
      effects of hantavirus infection and their consequences for pathogen dynamics,
      this study shows that the infection may have complex effects that are dependent
      on the age of the individual and the time of the breeding season.

PMID- 25965087
TI  - Cherenkov friction on a neutral particle moving parallel to a dielectric.
AB  - We describe a simple mechanism of quantum friction for a particle moving parallel
      to a dielectric, based on a fully relativistic framework and the assumption of
      local equilibrium. The Cherenkov effect explains how the bare ground state
      becomes globally unstable and how fluctuations of the electromagnetic field and
      the particle's dipole are converted into pairs of excitations. Modeling the
      particle as a silver nano-sphere, we investigate the spectrum of the force and
      its velocity dependence. We find that the damping of the plasmon resonance in the
      silver particle has a relatively strong impact near the Cherenkov threshold
      velocity. We also present an expansion of the friction force near the threshold
      velocity for both damped and undamped particles. 

PMID- 25965088
TI  - Full time-resolved diffuse fluorescence tomography accelerated with parallelized
      Fourier-series truncated diffusion approximation.
AB  - Of the three measurement schemes established for diffuse fluorescence tomography
      (DFT), the time-domain scheme is well known to provide the richest information
      about the distribution of the targeting fluorophore in living tissues. However,
      the explicit use of the full time-resolved data usually leads to a considerably
      lengthy time for image reconstruction, limiting its applications to three
      dimensional or small-volume imaging. To cope with the adversity, we propose
      herein a computationally efficient scheme for DFT image reconstruction where the
      time-dependent photon density is expanded to a Fourier-series and calculated by
      solving the independent frequency-domain diffusion equations at multiple sampling
      frequencies with the support of a combined multicore CPU-based coarse-grain and
      multithread GPU-based fine-grain parallelization strategy. With such a
      parallelized Fourier-series truncated diffusion approximation, both the time- and
      frequency-domain inversion procedures are developed and validated for their
      effectiveness and accuracy using simulative and phantom experiments. The results
      show that the proposed method can generate reconstructions comparable to the
      explicit time-domain scheme, with significantly reduced computational time.

PMID- 25965089
TI  - Guest editorial: Are you sure you want to be only a wound care nurse?

PMID- 25965090
TI  - Body Image Perceptions of Persons With a Stoma and Their Partners: A Descriptive,
      Cross-sectional Study.
AB  - The body image perceptions of persons with a stoma and their partners are rarely
      examined and have yet to be evaluated in a Turkish sample. Using convenience
      sampling methods, a descriptive, cross-sectional study was conducted among
      individuals receiving treatment at the authors' stomatherapy unit between March
      1, 2012 and May 31, 2012 to assess the effect of the stoma on self-image and
      partner perception. Eligible participants had to be >18 years of age, married,
      and with an abdominal stoma (colostomy, urostomy, or ileostomy) for at least 2
      months. Data were obtained through separate (patient or partner), face-to-face,
      30-minute to 45-minute interviews using the appropriate questionnaire.
      Questionnaire items assessed demographic variables and patient/partner feelings
      toward the ostomate's body using the Body Cathexis Scale (BCS) and author
      developed questionnaires comprising statements eliciting individual responses
      (agree, disagree, undecided) regarding their feelings toward the stoma. Data were
      tabulated and analyzed using percentile distributions, and Mann Whitney U and
      Kruskal Wallis H tests were performed (Bonferroni correction was applied). Sixty
      (60) patients (25 women, 35 men, mean age 56.01 +/- 10.1 years; 25 with an
      ileostomy, 30 with a colostomy, 5 with an ileostomy) participated, along with
      their 60 heterosexual partners (mean age 54.56 +/- 10.25 years) married a mean of
      33.06 +/- 11.03 years. Mean patient BCS score was 133.15 +/- 20.58 (range 40--low
      perception--to 200--high perception). Mean BCS score of patients whose partner
      helped in stoma care was significantly higher (136.04) than those whose partners
      did not (120.27) (P = 0.033). Patients who consulted their partners' opinions on
      stoma creation and participation in care had significantly higher BCS scores (P
      <0.05), and BCS scores of patients whose partners thought the stoma had a
      negative effect on their relationship were significantly lower (P = 0.040);
      patients' perceptions toward their bodies were parallel to their partners'. Mean
      BCS score of patients experiencing physical and psychosocial problems was
      significantly lower than those of patients who did not experience such problems.
      The results of this study show a number of factors, including involving patient
      partners before surgery, affect body perception of persons following stoma
      surgery.

PMID- 25965091
TI  - A prospective, randomized controlled trial comparing 3 dressing types following
      sternotomy.
AB  - Dressings are an important aspect of post-sternotomy care. A prospective,
      randomized, controlled trial was conducted between July 2010 and August 2012 to
      compare wound and patient outcomes among 3 marketed postoperative dressings.
      Using convenience sampling methods, 315 patients requiring a sternotomy incision
      followed by hospitalization were randomly assigned to postoperative care with a
      dry sterile (n = 106), metallic silver-containing (n = 105), or ionic silver
      containing (n = 104) dressing. Application time and ease of dressing application
      were assessed. The dry dressings remained in place for 24 to 48 hours. On
      postoperative day 5 or at time of discharge, the silver dressings were removed
      and wound outcomes (degree of wound approximation, skin integrity, wound exudate,
      presence/absence of necrotic tissue), presence/absence of surgical site
      infection, patient comfort, and dressing factors (ease of removal, dressing
      integrity) were evaluated. All participants received the same preoperative skin
      preparation and intravenous antibiotics. Data were analyzed using Fisher's exact
      chi-squares and 1-way ANOVA. No statistically significant differences were found
      among the dressings in terms of wound healing or infection rate, but
      statistically significant differences were noted in patient comfort and certain
      dressing factors. When comparing all 3 dressings, the dry sterile dressing took
      less time to apply (P = 0.000) and was easiest to apply (P = 0.000). Use of the
      metallic silver dressing resulted in the least patient-reported pain upon removal
      (P = 0.015), and incision assessment was easiest with the ionic silver dressing
      (P = 0.000). When comparing the 2 silver dressings, the metallic silver dressing
      was easiest to remove (P = 0.003) but had less integrity at the time of removal
      (P = 0.007). None of the patients in the ionic silver and 1 patient (1%) in the
      metallic silver dressing group developed a deep infection. Additional research is
      warranted to determine best practice in postoperative, clean surgical incision
      management, including sternotomy wounds.

PMID- 25965092
TI  - Early closure of temporary loop ileostomies: a systematic review.
AB  - A temporary loop ileostomy is a common surgical procedure to protect colorectal
      anastomoses. The aim of this systematic review was to determine whether early
      closure of a defunctioning loop ileostomy (<2 weeks from index operation) is safe
      and reduces stoma-related morbidity. A systematic literature search was conducted
      using Ovid MEDLINE, EMBASE, Cochrane Collaboration, and the Cumulative Index to
      Nursing and Allied Health (CINAHL(r)) databases to identify all publications from
      January 1996 to March 2014 that reported the outcomes of early ileostomy closure.
      The following search terms (and their variations) were used as both medical
      subject headings (MeSH terms) and text words: ileostomy, surgical stoma, stoma,
      early, reversal, closure. No language restrictions were applied. The main
      outcomes of interest were stoma-related complications and postclosure
      complications. Studies that included pediatric patients (<18 years of age), small
      cohorts (<10 participants), case reports, conference abstracts, reviews, and
      letters; studies involving defunctioning colostomies or other types of small
      bowel stomas; and studies where results from closure of an ileostomy at >14 days
      could not be separated from early closure results were excluded. Where multiple
      studies were reported by the same institution and/or authors, only the most
      recent was included. This search strategy identified 4 studies (2 retrospective
      case series, 1 prospective nonrandomized study, and 1 randomized controlled
      trial), yielding a pooled population of 142 patients, ages 18-89 years old. Three
      studies reported indication for ileostomy; colorectal cancer accounted for 96
      patients (78%). Time to ileostomy closure ranged from 8-14 days. No reported
      deaths were related to ileostomy closure. Wound infections were reported in 3
      studies and were the most common complications, affecting 24 patients (19.8%). Of
      the 2 studies that reported ileostomy-related complications, 4 patients (3.6%)
      experienced a stoma-related complication before closure. Ileus or small bowel
      obstruction (SBO) occurred in 7 patients (4.9%). Compared to traditionally timed
      closure (8-12 weeks), reported stoma-related complication rates were lower in
      patients undergoing early closure. Both mortality and ileus/SBO rates also
      compare favorably with traditionally timed closure; however, wound infection
      rates appear to be increased. Additional studies to accurately define which
      individuals stand to benefit from early closure, as well as to further evaluate
      the impact of early ileostomy closure on quality of life and health care costs,
      are warranted. 

PMID- 25965093
TI  - Inhibitory effects of platelet-rich plasma on intervertebral disc degeneration: a
      preclinical study in a rabbit model.
AB  - BACKGROUND: Platelet-rich plasma (PRP) contains multiple growth hormones that may
      stimulate tissue repair. This study aimed to assess the effects of PRP in a
      rabbit model of IDD (annulus fibrosus puncture). MATERIAL/METHODS: Thirty-six
      adult New Zealand white rabbits were randomly divided into 3 groups: 0.1 mL PRP
      (group A), 0.1 mL phosphate-buffered saline (group B), and control (group C)
      (n=12/group). Annulus fibrosus puncture was performed to establish L4/5 and L5/6
      IDD models. Two and 4 weeks later, 6 rabbits from each group were given an IVD
      injection at L4/5 and L5/6. Two or 4 weeks after injection, rabbits were scanned
      with X-ray and MRI before being sacrificed. IVDs were collected for hematoxylin
      and eosin, Masson's trichrome, and Safranin O staining, and type II collagen
      immunohistochemistry. RESULTS: Over time, IVD height and disc imaging signal
      intensity decreased gradually in groups B and C, but only slightly in group A
      (baseline: 100% for all groups; A: 95.9+/-4.2% at 4 weeks, 90.1+/-8.4 at 6 weeks;
      B: 75.3+/-5.7% at 4 weeks, 70.8+/-6.4% at 6 weeks; C: 74.7+/-5.5% at 4 weeks,
      69.9+/-6.2% at 6 weeks; all P<0.001, P<0.01 between A vs. B and C). Degenerative
      histological changes in IVDs in groups B and C were more severe compared with
      group A. CONCLUSIONS: Platelet-rich plasma interventions can effectively
      attenuate the IDD process in rabbits.

PMID- 25965094
TI  - Luminescence and single-molecule magnet behavior in lanthanide complexes
      involving a tetrathiafulvalene-fused dipyridophenazine ligand.
AB  - The reaction between the TTF-fused dipyrido[3,2-a:2',3'-c]phenazine (dppz) ligand
      (L) and 1 equiv of Ln(hfac)3.2H2O (hfac(-) = 1,1,1,5,5,5
      hexafluoroacetyacetonate) or 1 equiv of Ln(tta)3.2H2O (tta(-) = 2
      thenoyltrifluoroacetonate) (Ln(III) = Dy(III) or Yb(III)) metallic precursors
      leads to four mononuclear complexes of formula [Ln(hfac)3(L)].C6H14 (Ln(III) =
      Dy(III) (1), Yb(III) (2)) and [Ln(tta)3(L)].C6H14 (Ln(III) = Dy(III) (3), Yb(III)
      (4)), respectively. Their X-ray structures reveal that the Ln(III) ion is
      coordinated to the bischelating nitrogenated coordination site and adopts a D4d
      coordination environment. The dynamic magnetic measurements show a slow
      relaxation of the Dy(III) magnetization for 1 and 3 with parameters highlighting
      a slower relaxation for 3 than for 1 (tau0 = 4.14(+/-1.36) * 10(-6) and 1.32(+/
      0.07) * 10(-6) s with Delta = 39(+/-3) and 63.7(+/-0.7) K). This behavior as well
      as the orientation of the associated magnetic anisotropy axes have been
      rationalized on the basis of both crystal field splitting parameters and ab
      initio SA-CASSCF/RASSI-SO calculations. Irradiation of the lowest-energy HOMO ->
      LUMO ILCT absorption band induces a (2)F5/2 -> (2)F7/2 Yb-centered emission for 2
      and 4. For these Yb(III) compounds, Stevens operators method has been used to fit
      the thermal variation of the magnetic susceptibilities, and the resulting MJ
      splittings have been correlated with the emission lines. 

PMID- 25965095
TI  - Online Continuous Flow Differential Electrochemical Mass Spectrometry with a
      Realistic Battery Setup for High-Precision, Long-Term Cycling Tests.
AB  - We describe the benefits of an online continuous flow differential
      electrochemical mass spectrometry (DEMS) method that allows for realistic battery
      cycling conditions. We provide a detailed description on the buildup and the role
      of the different components in the system. Special emphasis is given on the cell
      design. The retention time and response characteristics of the system are tested
      with the electrolysis of Li2O2. Finally, we show a practical application in which
      a Li-ion battery is examined. The value of long-term DEMS measurements for the
      proper evaluation of electrolyte decomposition is demonstrated by an experiment
      where a Li(1+x)Ni(0.5)Mn(0.3)Co(0.2)O2 (NMC 532)/graphite cell is cycled over 20
      charge/discharge cycles.

PMID- 25965096
TI  - Influence of materials' optical response on actuation dynamics by Casimir forces.
AB  - The dependence of the Casimir force on the frequency-dependent dielectric
      functions of interacting materials makes it possible to tailor the actuation
      dynamics of microactuators. The Casimir force is largest for metallic interacting
      systems due to the high absorption of conduction electrons in the far-infrared
      range. For less conductive systems, such as phase change materials or conductive
      silicon carbide, the reduced force offers the advantage of increased stable
      operation of MEMS devices against pull-in instabilities that lead to unwanted
      stiction. Bifurcation analysis with phase portraits has been used to compare the
      sensitivity of a model actuator when the optical properties are altered. 

PMID- 25965097
TI  - Growth and Characterization of Al2O3 Atomic Layer Deposition Films on sp(2)
      Graphitic Carbon Substrates Using NO2/Trimethylaluminum Pretreatment.
AB  - The growth of Al2O3 films by atomic layer deposition (ALD) on model sp(2)
      graphitic carbon substrates was evaluated following a nitrogen dioxide (NO2) and
      trimethylaluminum (TMA) pretreatment to deposit an Al2O3 adhesion layer. Al2O3
      ALD using TMA and water (H2O) as the reactants was used to grow Al2O3 films on
      exfoliated highly ordered pyrolitic graphite (HOPG) at 150  degrees C with and
      without the pretreatment procedure consisting of five NO2/TMA cycles. The Al2O3
      films on HOPG substrates were evaluated using spectroscopic ellipsometry and
      electrochemical analysis to determine film thickness and quality. These
      experiments revealed that five NO2/TMA cycles at 150  degrees C deposited an
      Al2O3 adhesion layer with a thickness of 5.7 +/- 3.6 A on the HOPG substrate. A
      larger number of NO2/TMA cycles at 150  degrees C deposited thicker Al2O3 films
      until reaching a limiting thickness of ~80 A. Electrochemical impedance
      spectroscopy (EIS) measurements revealed that five cycles of NO2/TMA pretreatment
      enabled the growth of high quality insulating Al2O3 films with high charge
      transfer resistance after only 20 TMA/H2O Al2O3 ALD cycles. In contrast, with no
      NO2/TMA pretreatment, EIS measurements indicated that 100 TMA/H2O Al2O3 ALD
      cycles were necessary to produce an insulating Al2O3 film with high charge
      transfer resistance. Al2O3 films grown after the NO2/TMA pretreatment at 150 
      degrees C were also demonstrated to have better resistance to dissolution in an
      aqueous environment. 

PMID- 25965098
TI  - G-arylated hydrogen-bonded cyclic tetramer assemblies with remarkable
      thermodynamic and kinetic stability.
AB  - The preparation and self-assembly of novel G-C dinucleoside monomers that are
      equipped with electron-poor aryl groups at the G-N(2) amino group have been
      studied. Such monomers associate via Watson-Crick H-bonding into discrete
      unstrained tetrameric macrocycles that arise as a thermodynamically and
      kinetically stabilized product in a wide variety of experimental conditions,
      including very polar solvent environments and low concentrations. G-arylation
      produces an increased stability of the cyclic assembly, as a result of a subtle
      interplay between enthalpic and entropic effects involving the solvent
      coordination sphere. 

PMID- 25965099
TI  - Heterogeneities in Cholesterol-Containing Model Membranes Observed by Pulsed
      Electron Paramagnetic Resonance of Spin Labels.
AB  - Biological membranes are supposed to have heterogeneous structure containing
      lipid rafts-lateral micro- and nanodomains enriched in cholesterol (chol) and
      sphingolipids. In this work, lipid bilayers containing a small amount of the spin
      labeled chol analogue 3beta-doxyl-5alpha-cholestane (chlstn) were studied using
      electron spin echo (ESE) spectroscopy, which is a pulsed version of electron
      paramagnetic resonance (EPR). Bilayers were prepared from an equimolecular
      mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dioleoyl-sn
      glycero-3-phosphocholine (DOPC) with chol added at different concentrations. The
      ESE decays recorded at 77 K become faster with increase of chlstn concentration.
      The chlstn-dependent contribution to ESE decay is remarkably nonexponential;
      however, the logarithm of this contribution can be rescaled for different chlstn
      concentrations to a universal function with the rescaling factor approximately
      proportional to concentration. This result shows that the chlstn-dependent
      contribution to the ESE decay can be employed to estimate the local (at the
      nanometer scale of distances) chlstn concentration. Analogous rescaling behavior
      is also observed for the bilayers with different chol concentrations, with the
      rescaling factor increasing with increase of the chol concentration. This result
      is evidence that chlstn molecules are distributed heterogeneously in the chol
      containing bilayer and form clusters with enhanced chlstn (and probably chol)
      local concentration. The local concentration of chlstn molecules for large chol
      content (~30 mol %) was enhanced by at least ~70% versus chol-free bilayers. The
      suggested approach appears to be useful for exploring heterogeneities in lipid
      composition of biological membranes of different types. 

PMID- 25965100
TI  - Gap and channeled plasmons in tapered grooves: a review.
AB  - Tapered metallic grooves have been shown to support plasmons -
      electromagnetically coupled oscillations of free electrons at metal-dielectric
      interfaces - across a variety of configurations and V-like profiles. Such
      plasmons may be divided into two categories: gap-surface plasmons (GSPs) that are
      confined laterally between the tapered groove sidewalls and propagate either
      along the groove axis or normal to the planar surface, and channeled plasmon
      polaritons (CPPs) that occupy the tapered groove profile and propagate
      exclusively along the groove axis. Both GSPs and CPPs exhibit an assortment of
      unique properties that are highly suited to a broad range of cutting-edge
      nanoplasmonic technologies, including ultracompact photonic circuits, quantum
      optics components, enhanced lab-on-a-chip devices, efficient light-absorbing
      surfaces and advanced optical filters, while additionally affording a niche
      platform to explore the fundamental science of plasmon excitations and their
      interactions. In this Review, we provide a research status update of plasmons in
      tapered grooves, starting with a presentation of the theory and important
      features of GSPs and CPPs, and follow with an overview of the broad range of
      applications they enable or improve. We cover the techniques that can fabricate
      tapered groove structures, in particular highlighting wafer-scale production
      methods, and outline the various photon- and electron-based approaches that can
      be used to launch and study GSPs and CPPs. We conclude with a discussion of the
      challenges that remain for further developing plasmonic tapered-groove devices,
      and consider the future directions offered by this select yet potentially far
      reaching topic area. 

PMID- 25965101
TI  - On-water remote monitoring robotic system for estimating the patch coverage of
      Anabaena sp. filaments in shallow water.
AB  - An on-water remote monitoring robotic system was developed for indirectly
      estimating the relative density of marine cyanobacteria blooms at the subtidal
      sandy-rocky beach in Balandra Cove, Baja California Sur, Mexico. The system is
      based on an unmanned surface vehicle to gather underwater videos of the seafloor
      for avoiding physical damage on Anabaena sp. cyanobacteria colonies, which grow
      in tufts of filaments weakly attached to rocks, seagrass, and macroalgae. An on
      axis image stabilization mechanism was developed to support a camcorder and
      minimize wave perturbation while recording underwater digital images of the
      seafloor. Color image processing algorithms were applied to estimate the patch
      coverage area and density, since Anabaena sp. filaments exhibit a characteristic
      green tone. Results of field tests showed the feasibility of the robotic system
      to estimate the relative density, distribution, and coverage area of
      cyanobacteria blooms, preventing the possible impact of direct observation. The
      robotic system could also be used in surveys of other benthos in the sublittoral
      zone. 

PMID- 25965103
TI  - Chromogenic/Fluorogenic Ensemble Chemosensing Systems.

PMID- 25965104
TI  - Folding Patterns in a Family of Oligoamide Foldamers.
AB  - A series of small, unsymmetrical pyridine-2,6-dicarboxylamide oligoamide
      foldamers with varying lengths and substituents at the end groups were
      synthetized to study their conformational properties and folding patterns. The @
      type folding pattern resembled the oxyanion-hole motifs of enzymes, but several
      alternative folding patterns could also be characterized. Computational studies
      revealed several alternative conformers of nearly equal stability. These folding
      patterns differed from each other in their intramolecular hydrogen-bonding
      patterns and aryl-aryl interactions. In the solid state, the foldamers adopted
      either the globular @-type fold or the more extended S-type conformers, which
      were very similar to those foldamers obtained computationally. In some cases, the
      same foldamer molecule could even crystallize into two different folding
      patterns, thus confirming that the different folding patterns are very close in
      energy in spite of their completely different shapes. Finally, the best match for
      the observed NOE interactions in the liquid state was a conformation that matched
      the computationally characterized helix-type fold. 

PMID- 25965105
TI  - Effect of a second primary thyroid carcinoma on patients with head and neck
      squamous cell carcinoma.
AB  - BACKGROUND: The purpose of this study was to characterize the timing, histology,
      and behavior of second primary thyroid carcinoma (SPTC) developing after a
      diagnosis of head and neck squamous cell carcinoma (HNSCC). METHODS: We conducted
      a retrospective review of the Surveillance, Epidemiology, and End Results (SEER)
      9 database. RESULTS: Patients with HNSCC who develop SPTC die 1.6 times sooner
      than those without SPTC. This effect is only seen if SPTC presents >6 months
      after diagnosis of HNSCC. Models were adjusted for age, sex, year of diagnosis,
      and location of HNSCC. There was no effect of prior radiation therapy on either
      mortality rates or time to development of thyroid cancer in patients with SPTC.
      The type of thyroid carcinoma that developed was similar between cohorts.
      CONCLUSION: The development of SPTC in patients with HNSCC results in decreased
      overall length of survival. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E890
      E894, 2016.

PMID- 25965106
TI  - Pathways for the OH + Cl2 -> HOCl + Cl and HOCl + Cl -> HCl + ClO Reactions.
AB  - High level coupled-cluster theory, with spin-orbit coupling evaluated via the
      Breit-Pauli operator in the interacting-states approach, is used to investigate
      the OH radical reaction with Cl2 and the subsequent reaction HOCl + Cl. The
      entrance complex, transition state, and exit complex for both reactions have been
      determined using the CCSD(T) method with correlation consistent basis sets up to
      cc-pV6Z. Also reported are CCSDT computations. The OH + Cl2 reaction is predicted
      to be endothermic by 2.2 kcal/mol, compared to the best experiments, 2.0
      kcal/mol. The above theoretical results include zero-point vibrational energy
      corrections and spin-orbit contributions. The activation energy (Ea) of the OH +
      Cl2 reaction predicted here, 2.3 kcal/mol, could be as much as 1 kcal/mol too
      high, but it falls among the four experimental Ea values, which span the range
      1.1-2.5 kcal/mol. The exothermicity of the second reaction HOCl + Cl -> HCl + ClO
      is 8.4 kcal/mol, compared to experiment 8.7 kcal/mol. The activation energy for
      latter reaction is unknown experimentally, but predicted here to be large, 11.5
      kcal/mol. There are currently no experiments relevant to the theoretical entrance
      and exit complexes predicted here. 

PMID- 25965107
TI  - A Nanoscale Multiresponsive Luminescent Sensor Based on a Terbium(III) Metal
      Organic Framework.
AB  - A nanoscale terbium-containing metal-organic framework (nTbL), with a layer-like
      structure and [H2 NMe2 ](+) cations located in the framework channels, was
      synthesized under hydrothermal conditions. The structure of the as-prepared
      sample was systematically confirmed by powder XRD and elemental analysis; the
      morphology was characterized by field-emission SEM and TEM. The photoluminescence
      studies revealed that rod-like nTbL exhibited bright-green emission,
      corresponding to (5)D4 ->(7)FJ (J=6-3) transitions of the Tb(3+) ion under
      excitation. Further sensing measurements revealed that as-prepared nTbL could be
      utilized as a multiresponsive luminescent sensor, which showed significant and
      exclusive detection ability for Fe(3+) ions and phenylmethanol. These results
      highlight the practical applications of lanthanide-containing metal-organic
      frameworks as fluorescent probes.

PMID- 25965108
TI  - The acute effects of yoga on cognitive measures for women with premenstrual
      syndrome.
AB  - OBJECTIVES: Recently, yoga classes specifically for women with premenstrual
      syndrome (PMS) have increased, but there is little research about the efficacy of
      these classes. The primary aims of this study were to evaluate the effect of yoga
      exercise on women with PMS and to evaluate the immediate change of attention
      performance after yoga classes. METHODS: This study examined the attention task
      results of women with PMS. Eleven women with PMS and 9 women without PMS were
      recruited. The PMS group took the tests before and immediately after the yoga
      class both in the luteal and follicular phase of one menstrual cycle, while the
      control group took the tests only twice: once in the luteal phase and once in the
      follicular phase. Both groups were required to finish resting
      electroencephalography (EEG) and cognitive task of the 2-back task with EEG
      recording. RESULTS: The alpha brain wave percentage was higher immediately after
      yoga exercise in the PMS group. This suggests that the participants felt more
      relaxed or were in a more peaceful mental condition after yoga exercise. In the 2
      back task, the PMS group needed a longer reaction time to respond to the target
      stimulus in the luteal phase and performed better with higher accuracy and
      shorter reaction time after yoga exercise. The event-related potentials of the
      EEG recording displayed a significant variability at the P3 amplitude throughout
      the menstrual cycle in the PMS group, but the P3 amplitude was unchanged
      throughout the menstrual cycle in the control group. CONCLUSION: The results of
      this study suggest that women with PMS could attend short-term yoga exercise in
      the luteal phase to make themselves feel better and maintain a better attention
      level.

PMID- 25965109
TI  - Comparison of heat-induced aggregation of globular proteins.
AB  - Typically, heat-induced aggregation of proteins is studied using a single protein
      under various conditions (e.g., temperature). Because different studies use
      different conditions and methods, a mechanistic relationship between molecular
      properties and the aggregation behavior of proteins has not been identified.
      Therefore, this study investigates the kinetics of heat-induced aggregation and
      the size/density of formed aggregates for three different proteins (ovalbumin,
      beta-lactoglobulin, and patatin) under various conditions (pH, ionic strength,
      concentration, and temperature). The aggregation rate of beta-lactoglobulin was
      slower (>10 times) than that of ovalbumin and patatin. Moreover, the conditions
      (pH, ionic strength, and concentration) affected the aggregation kinetics of beta
      lactoglobulin more strongly than for ovalbumin and patatin. In contrast to the
      kinetics, for all proteins the aggregate size/density increased with decreasing
      electrostatic repulsion. By comparing these proteins under these conditions, it
      became clear that the aggregation behavior cannot easily be correlated to the
      molecular properties (e.g., charge and exposed hydrophobicity). 

PMID- 25965110
TI  - Difficult-to-cure populations with chronic hepatitis C: Vanishing in the direct
      acting antiviral era?

PMID- 25965111
TI  - Parallels between nutrition and physical activity: research questions in
      development of peak bone mass.
AB  - Lifestyle choices are attributed to 40% to 60% of adult peak bone mass. The
      National Osteoporosis Foundation (NOF) sought to update its 2000 consensus
      statement on peak bone mass and partnered with the American Society for
      Nutrition, which, in turn, charged a 9-member writing committee with using a
      systematic review approach to update the previous NOF guidelines. PubMed searches
      of the scientific literature from January 2000 through December 2014 were
      conducted on all relevant lifestyle choice factors and their relation to
      increasing bone mass during childhood and adolescence. The writing group
      concluded that there is strong evidence for the benefits of physical activity and
      calcium intake on bone mass accretion, moderately strong evidence for the
      benefits of vitamin D and dairy intake on bone mass and for physical activity on
      bone structure, and weaker evidence for other lifestyle choices. There were
      parallels and synergies between the benefits of diet and exercise on development
      of peak bone mass, but the type of evidence and public policy recommendations in
      the two disciplines differ in several important ways. Nutrition uses a more
      reductionist approach in contrast to physical activity, which uses a more global
      approach. This leads to differences in research priorities in the 2 disciplines.
      The disciplines can advance more quickly through collaboration and adoption of
      the best approaches from each other. 

PMID- 25965112
TI  - Does framing the hot hand belief change decision-making behavior in volleyball?
AB  - PURPOSE: Previous discussions of the hot hand belief, wherein athletes believe
      that they have a greater chance of scoring after 2 or 3 hits (successes) compared
      with 2 or 3 misses, have focused on whether this is the case within game
      statistics. Researchers have argued that the perception of the hot hand in random
      sequences is a bias of the cognitive system. Yet most have failed to explore the
      impact of framing on the stability of the belief and the behavior based on it.
      METHOD: The authors conducted 2 studies that manipulated the frame of a judgment
      task. In Study 1, framing was manipulated via instructions in a playmaker
      allocation paradigm in volleyball. In Study 2, the frame was manipulated by
      presenting videos for allocation decisions from either the actor or observer
      perspective. RESULTS: Both manipulations changed the hot hand belief and
      sequential choices. We found in both studies that the belief in continuation of
      positive or negative streaks is nonlinear and allocations to the same player
      after 3 successive hits are reduced. CONCLUSIONS: The authors argue that neither
      the hot hand belief nor hot hand behavior is stable, but rather, both are
      sensitive to decision frames. The results can inform coaches on the importance of
      how to provide information to athletes.

PMID- 25965113
TI  - A global viability assessment of the European eel.
AB  - The global European eel (Anguilla anguilla) stock is critically endangered
      according to the IUCN, and the European Commission has urged the development of
      conservation plans aimed to ensure its viability. However, the complex life cycle
      of this panmictic species, which reproduces in the open ocean but spends most of
      its prereproductive life in continental waters (thus embracing a huge geographic
      range and a variety of habitat types), makes it difficult to assess the long-term
      effectiveness of conservation measures. The interplay between local and global
      stressors raises intriguing cross-scale conservation challenges that require a
      comprehensive modelling approach to be addressed. We developed a full life cycle
      model of the global European eel stock, encompassing both the oceanic and the
      continental phases of eel's life, and explicitly allowing for spatial
      heterogeneity in vital rates, availability of suitable habitat and settlement
      potential via a metapopulation approach. We calibrated the model against a long
      term time series of global European eel catches and used it to hindcast the
      dynamics of the stock in the past and project it over the 21st century under
      different management scenarios. Although our analysis relies on a number of
      inevitable simplifying assumptions and on data that may not embrace the whole
      range of variation in population dynamics at the small spatiotemporal scale, our
      hindcast is consistent with the general pattern of decline of the stock over
      recent decades. The results of our projections suggest that (i) habitat loss
      played a major role in the European eel decline; (ii) the viability of the global
      stock is at risk if appropriate protection measures are not implemented; (iii)
      the recovery of spawner escapement requires that fishing mortality is
      significantly reduced; and (iv) the recovery of recruitment might not be feasible
      if reproductive output is not enhanced. 

PMID- 25965114
TI  - Mental and behavioral health conditions among older adults: implications for the
      home care workforce.
AB  - OBJECTIVES: The shift towards home and community-based care, coupled with the
      growing prevalence of mental and behavioral health conditions, increases the
      demand for skilled home care workers. However, little is known about the
      experiences of home care aides who provide care to clients with mental and
      behavioral health diagnoses. The purpose of this study was to identify challenges
      aides face in providing care to this particular group of clients, as well as the
      strategies and support they utilize to complete their job responsibilities.
      METHODS: Data from five focus groups with home care workers (N = 49) throughout
      Massachusetts were used to examine the experiences of home care workers providing
      services to adults with mental or behavioral health needs. A constant comparative
      method was used during analysis of the focus group transcripts. RESULTS: Aides
      described a lack of prior-knowledge of challenging client behaviors, leaving them
      unprepared to deal with disruptions to care delivery. Aides feel unsafe or unsure
      providing care to someone with complex needs, made worse by a perceived lack of
      training and support from the broader care team. Aides develop unique strategies
      for accomplishing their work. CONCLUSION: This analysis of the aide's perspective
      contributes valuable, and often unheard, insight to inform what we know about
      providing reliable, quality and safe home care to this growing group of
      vulnerable adults. Implications of this convergence are discussed relative to
      aides.

PMID- 25965115
TI  - Seroprevalence of hepatitis E in HIV infected patients in Greece.
AB  - HEV infection is an emerging public health problem worldwide Data concerning HEV
      infection in HIV+ patients in Greece is scare. The aim of the study was to
      determine HEV seroprevalence in patients with HIV infection in Greece. We studied
      243 HIV(+) patients 214 men (88%) and 29 women (12%) with a median age of 45
      years (range 19-83) who attended the HIV unit of Pathophysiology Department of
      Laikon General Hospital in Athens for the presence of anti-HEV IgG antibodies
      with (EIA) (EIA HEV IgG, Adaltis, Rome, Italy Eighteen/243 patients (7.3%) were
      positive for HEV IgG antibodies, a seroprevalence that was not different from
      that described for the blood donors group from Greece There was no difference of
      the presence of HbsAg, hepatitis C and hepatitis A between the HEV(+) and HEV(-)
      patients. There was no statistically significant difference between the HEV(+)
      and HEV(-) group in terms of HIV acquisition, sexual orientation, median duration
      of HIV infection, ART treatment, or duration of ART. Only the median age of
      HEV(+) was 52 years (35-78) while that of HEV(-) was 44 years (19-83)(P = 0.03).
      Only 2/18(11.1%) HEV(+) HIV(+) patients had abnormal ALT and AST values. The
      seroprevalence of hepatitis E in HIV(+) patients in Greece seems to be the same
      with that of the general population thus implying that HIV infection is not a
      risk factor for HEV infection and only age shows a positive correlation with
      seropositivity.

PMID- 25965116
TI  - Protective effects of Nitraria retusa extract and its constituent isorhamnetin
      against amyloid beta-induced cytotoxicity and amyloid beta aggregation.
AB  - Nitraria retusa is a halophyte species that is distributed in North Africa and
      used as a traditional medicinal plant. In this study, N. retusa ethanol extract
      and its constituent isorhamnetin (IRA) protected against amyloid beta (Abeta)
      induced cytotoxicity in human neuroblastoma SH-SY5Y cells. An in vitro Abeta
      aggregation assay suggested that IRA destabilizes Abeta fibrils.

PMID- 25965117
TI  - Monodisperse sandwich-like coupled quasi-graphene sheets encapsulating ni2 p
      nanoparticles for enhanced lithium-ion batteries.
AB  - In this report, sandwiched Ni2 P nanoparticles encapsulated by graphene sheets
      are first synthesized by directly encapsulating functional units in graphene
      sheets instead of fabricating separate graphene sheets and then immobilizing the
      functional components onto the generated surfaces. In this strategy, we use low
      cost, sustainable and environmentally friendly glucose as a carbon source and
      NiNH4 PO4 ?H2 O nanosheets as sacrificial templates. This unique structure
      obtained here cannot only prevent the nanoparticles from aggregation or loss but
      also enhance the electronic conductivity compared to the independent
      nanoparticles. Furthermore, the novel sandwich-like Ni2 P/C can be applied in
      plenty of fields, especially in electrical energy storage. In this paper, a
      series of electrochemical tests of the sandwich-like Ni2 P/C are carried out,
      which demonstrate the excellent cyclic stability and rate capacity for lithium
      ion batteries. 

PMID- 25965118
TI  - Maxillary Sinus Membrane Repair With Amnion-Chorion Barriers: A Retrospective
      Case Series.
AB  - BACKGROUND: Schneiderian membrane perforation is the most common complication of
      maxillary sinus augmentation procedures and has been associated with a variety of
      post-surgical problems. Multiple techniques to repair perforated Schneiderian
      membranes with materials such as connective tissue, buccal fat pads, and
      resorbable collagen membranes have been reported in the dental literature.
      Although these reparative options have proven successful, they are technique
      sensitive and time consuming. The aim of this case series is to present a
      simplified method of Schneiderian membrane perforation repair with amnion-chorion
      membranes and results obtained from nine cases using this technique. METHODS: A
      consecutive retrospective record review was performed of all maxillary sinus
      augmentation cases performed during the past 5 years by the same board-certified
      private practice periodontist (DH). RESULTS: Seventy-seven cases were identified,
      with a total of 104 sinus augmentations, in which nine perforations were noted.
      None of the perforation cases were aborted midprocedure, and all perforations
      were repaired with amnion-chorion membranes. All cases were augmented with a
      combination of allograft and xenograft particulate bone. After an average healing
      time of 4.9 months, dental implants were placed in the grafted sinuses.
      CONCLUSIONS: This retrospective case series shows nine perforations during 104
      lateral window maxillary sinus augmentation procedures. A total of 23 dental
      implants were placed in the augmented sinuses with perforated Schneiderian
      membranes, and one failure was noted according the Albrektsson success criteria.
      A total of 158 dental implants were placed in non-perforated augmented sinuses,
      with a total of three failures noted.

PMID- 25965120
TI  - Transfer of linear momentum from the quantum vacuum to a magnetochiral molecule.
AB  - In a recent publication we have shown using a QED approach that, in the presence
      of a magnetic field, the quantum vacuum coupled to a chiral molecule provides a
      kinetic momentum directed along the magnetic field. Here we explain the physical
      mechanisms which operate in the transfer of momentum from the vacuum to the
      molecule. We show that the variation of the molecular kinetic energy originates
      from the magnetic energy associated with the vacuum correction to the
      magnetization of the molecule. We carry out a semiclassical calculation of the
      vacuum momentum and compare the result with the QED calculation.

PMID- 25965121
TI  - All-magnetic control of skyrmions in nanowires by a spin wave.
AB  - Magnetic skyrmions are topologically protected nanoscale objects, which are
      promising building blocks for novel magnetic and spintronic devices. Here, we
      investigate the dynamics of a skyrmion driven by a spin wave in a magnetic
      nanowire. It is found that (i) the skyrmion is first accelerated and then
      decelerated exponentially; (ii) it can turn L-corners with both right and left
      turns; and (iii) it always turns left (right) when the skyrmion number is
      positive (negative) in the T- and Y-junctions. Our results will be the basis of
      skyrmionic devices driven by a spin wave. 

PMID- 25965123
TI  - Combined metformin-clomiphene in clomiphene-resistant polycystic ovary syndrome:
      a systematic review and meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: Our objective was to compare the effectiveness of metformin plus
      clomiphene citrate vs. gonadotrophins, laparoscopic ovarian diathermy, aromatase
      inhibitors, N-acetyl-cysteine and other insulin sensitizers+clomiphene for
      improving fertility outcomes in women with clomiphene-resistant polycystic ovary
      syndrome. DESIGN: PubMed, SCOPUS and CENTRAL databases were searched until April
      2014 with the key words: PCOS, polycystic ovary syndrome, metformin, clomiphene
      citrate, ovulation induction and pregnancy. The search was limited to articles
      conducted with humans and published in English. SAMPLE: The PRISMA statement was
      followed. Twelve randomized controlled trials (n = 1411 women) were included.
      MAIN OUTCOME MEASURES: Ovulation and clinical pregnancy rates per woman
      randomized. RESULTS: Compared with gonadotrophins, the metformin+clomiphene
      combination resulted in significantly fewer ovulations (odds ratio 0.25; 95%
      confidence interval 0.15-0.41; p < 0.00001, 3 trials, I(2) = 85%, n = 323) and
      pregnancies (odds ratio 0.45; 95% confidence interval 0.27-0.75; p = 0.002, 3
      trials, I(2) = 0%, n = 323). No significant differences were found when
      metformin+clomiphene was compared with laparoscopic ovarian diathermy (odds ratio
      0.88; 95% confidence interval 0.53-1.47; p = 0.62, 1 trial, n = 282; odds ratio
      0.96; 95% confidence interval 0.60-1.54; p = 0.88, 2 trials, I(2) = 0%, n = 332,
      for ovulation and pregnancy rates, respectively). Likewise, no differences were
      observed in comparison with aromatase inhibitors (odds ratio 0.88; 95% confidence
      interval 0.58-1.34; p = 0.55, 3 trials, I(2) = 3%, n = 409; odds ratio 0.85; 95%
      confidence interval 0.53-1.36; p = 0.50, 2 trials, n = 309, for ovulation and
      pregnancy rates, respectively). CONCLUSIONS: There is evidence for the
      superiority of gonadotrophins, but the metformin+clomiphene combination is mainly
      relevant for clomiphene-resistant polycystic ovary syndrome patients and, if not
      effective, a next step could be gonadotrophins. More attempts with
      metformin+clomiphene are only relevant if there is limited access to
      gonadotrophins.

PMID- 25965122
TI  - Genetic markers associated with cutaneous adverse drug reactions to allopurinol:
      a systematic review.
AB  - Pharmacogenomic markers in the HLA coding genes have been associated with drug
      hypersensitivity of multiple drugs, including allopurinol. In this systematic
      review, we summarize the pharmacogenomic evidence available regarding allopurinol
      induced cutaneous adverse drug reactions (cADRs). We found that the HLA-B*5801
      allele was significantly associated with the risk of severe cADRs in the Han
      Chinese, Korean, Thai, Japanese and European populations. The association between
      less severe cADRs and HLA-B*5801 was less consistent. All SNPs identified in
      genome-wide association studies of common variants were also located in or nearby
      HLA-B*5801. Future studies should focus on more common but less severe
      allopurinol-induced cADRs, as well as the potential role of rare variants as
      predictors of these cADRs. 

PMID- 25965124
TI  - Esophageal motility disorders.
AB  - The diagnosis of esophageal motility disorders has been greatly enhanced with the
      development of high-resolution esophageal manometry studies and the Chicago
      Classification. Both hypomotility disorders and hypercontractility disorders of
      the esophagus have new diagnostic criteria. For the foregut surgeon, new
      diagnostic criteria for esophageal motility disorders have implications for
      decision-making during fundoplication and may expand the role of surgical therapy
      for esophageal achalasia by clarifying diagnostic criteria. 

PMID- 25965125
TI  - Approach to patients with esophageal Dysphagia.
AB  - Patients frequently present to a physician with complaints of difficulty
      swallowing. The approach to systematically evaluating these problems can be
      challenging for those who do not manage this type of patient regularly. The
      potential for life-threatening malignancies is present and makes this evaluation
      a priority. Numerous excellent tools are available to aid with the determination
      of the cause of dysphagia and assist with the formulation of a logical treatment
      algorithm. 

PMID- 25965126
TI  - Benign esophageal tumors.
AB  - Benign esophageal and paraesophageal masses and cysts are a rare but important
      group of pathologies. Although often asymptomatic, these lesions can cause a
      variety of symptoms and, in some cases, demonstrate variable biological behavior.
      Contemporary categorization relies heavily on endoscopic ultrasound and other
      imaging modalities and immunohistochemical analysis when appropriate. Minimally
      invasive options including endoscopic, laparoscopic, and thoracoscopic methods
      are increasingly used for symptomatic or indeterminate lesions. 

PMID- 25965127
TI  - Physiology and pathogenesis of gastroesophageal reflux disease.
AB  - Gastroesophageal reflux disease (GERD) is one of the most common problems treated
      by primary care physicians. Almost 20% of the population in the United States
      experiences occasional regurgitation, heartburn, or retrosternal pain because of
      GERD. Reflux disease is complex, and the physiology and pathogenesis are still
      incompletely understood. However, abnormalities of any one or a combination of
      the three physiologic processes, namely, esophageal motility, lower esophageal
      sphincter function, and gastric motility or emptying, can lead to GERD. There are
      many diagnostic and therapeutic approaches to GERD today, but more studies are
      needed to better understand this complex disease process. 

PMID- 25965128
TI  - Surgical treatment of gastroesophageal reflux disease.
AB  - Operative treatment of GERD has become more common since the introduction of
      LARS. Careful patient selection based on symptoms, response to medical therapy,
      and preoperative testing will optimize the chances for effective and durable
      postoperative control of symptoms. Complications of the LARS are rare and
      generally can be managed without reoperation. When reoperation is necessary for
      failed antireflux surgery, it should be performed by high-volume gastroesophageal
      surgeons.

PMID- 25965129
TI  - Paraesophageal hernia.
AB  - The treatment of PEHs is challenging. They tend to occur in patients in their 60s
      and 70s with multiple medical problems and a variety of associated symptoms.
      Detailed preoperative evaluation is crucial to determining a safe and effective
      strategy for repair in the operating room. Laparoscopic PEH repair has shown to
      be advantageous compared with conventional open repair with regard to hospital
      stay, recovery time, and decreased complications. Although some results indicate
      there are higher recurrence rates in laparoscopic PEH repair, the clinical
      significance of these recurrences has not yet been determined. In order to
      maximize the efficacy of this procedure, modifications have emerged, such as
      performing a fundoplication and using an absorbable mesh onlay to reinforce the
      cruroplasty. Althoughmoreprospective, randomized studies are needed to support
      the superior results of these surgical adjuncts, laparoscopic PEH repair with an
      antireflux procedure and absorbable mesh should be the current standard of care.

PMID- 25965130
TI  - Endoscopic dilatation, heller myotomy, and peroral endoscopic myotomy: treatment
      modalities for achalasia.
AB  - At present, LHM with partial fundoplication is considered the gold standard for
      the treatment of patients with esophageal achalasia. Endoscopic procedures such
      as EBTI and PD should be considered as primary treatment modalities only in frail
      patients. POEM is a new approach with promising short-term results.

PMID- 25965131
TI  - Gastroesophageal reflux disease after bariatric procedures.
AB  - GERD is a significant comorbidity in bariatric patients preoperatively and
      postoperatively. Surgeons should be aware of appropriate evaluation, procedures
      choices, and management options. Revision surgery for reflux symptoms is common
      and appropriate anatomy and outcomes should be considered when offering these
      interventions to our patients. Patient selection is important to ensure avoiding
      postoperative development or worsening of GERD.

PMID- 25965132
TI  - Barrett esophagus.
AB  - Although there are many unanswered questions with Barrett esophagus, we can
      safely say that the incidence is increasing, chemoprevention strategies for the
      prevention of Barrett metaplasia and its progression to adenocarcinoma may be in
      the offing, surveillance should be considered for all patients who are discovered
      to have Barrett esophagus, RFA is the treatment of choice for those with HGD and
      strongly considered in those with LGD, EMR should be the treatment of choice for
      patients with nodular high-grade Barrett esophagus, and, finally, vagal-sparing
      esophagectomy reserved for patients with persistent HGD or a strong suspicion of
      carcinoma, with consideration of a concomitant fundoplication.

PMID- 25965133
TI  - Minimally invasive esophagectomy for benign disease.
AB  - MIE can provide patients with reduced morbidity and a rapid recovery in the
      treatment of benign conditions. There is few data examining the long-term
      outcomes of MIE specifically in the context of benign disease. At present, MIE
      should be performed in centers with experience in advanced minimally invasive
      esophageal surgery, and it requires a team approach. Multicenter, prospective
      randomized controlled trials will be required to determine the superiority of MIE
      compared with open esophagectomy. Further investigation will be required to
      determine the effect of MIE on quality of life and long-term outcomes in the
      treatment of benign conditions.

PMID- 25965134
TI  - Preoperative evaluation of gastroesophageal reflux disease.
AB  - GERD is a common problem. If prolonged therapy is needed, the patient should have
      at least an endoscopy to assess for complications of GERD. If a surgical
      treatment is being considered, a thorough preoperative evaluation should be done
      to confirm the presence of pathologic GERD. Studies that should be done before a
      procedure include ambulatory pH testing, esophageal function testing, endoscopy,
      and esophagram. Nonacid ambulatory studies can be done in those who seem to be
      suffering from nonacid reflux with careful note of symptom correlation. Gastric
      emptying studies should be done if gastroparesis or gastric outlet obstruction is
      suspected. Esophageal motility disorders should be assessed with manometry,
      especially to evaluate for achalasia, which can mimic reflux.

PMID- 25965135
TI  - Reoperative antireflux surgery.
AB  - Patient satisfaction with primary antireflux surgery is high, but a small
      percentage of patients experience recurrent reflux and dysphagia, requiring
      reoperation. The major anatomic causes of failed fundoplication are slipped
      fundoplication, failure to identify a short esophagus, and problems with the
      wrap. Minimally invasive surgery has become more common for these procedures.
      Options for surgery include redo fundoplication with hiatal hernia repair if
      needed, conversion to Roux-en-Y anatomy, or, as a last resort, esophagectomy.
      Conversion to Roux-en-Y anatomy has a high rate of success, making this approach
      an important option in the properly selected patient. 

PMID- 25965136
TI  - Short esophagus.
AB  - In the presence of long-standing and severe gastroesophageal reflux disease,
      patients can develop various complications, including a shortened esophagus.
      Standard preoperative testing in these patients should include endoscopy,
      esophagography, and manometry, whereas the objective diagnosis of a short
      esophagus must be made intraoperatively following adequate mediastinal
      mobilization. If left untreated, it is a contributing factor to the high
      recurrence rate following fundoplications or repair of large hiatal hernias. A
      laparoscopic Collis gastroplasty combined with an antireflux procedure offers
      safe and effective therapy. 

PMID- 25965137
TI  - Endoscopic treatment of gastroesophageal reflux disease.
AB  - Multiple new endoluminal devices and therapies have been devised to create a more
      effective antireflux barrier in patients with gastroesophageal reflux disease
      (GERD). Most of these therapies have been abandoned, because they were
      ineffective and/or had significant adverse effects. However, there are currently
      two therapies (Stretta, EsophyX) that have US Food and Drug Administration
      approval and continue to be used in select patients with GERD. The clinical
      management of GERD, disease complications, endoluminal techniques, evidence for
      efficacy, and controversies concerning endoluminal therapy for GERD are reviewed
      and discussed. 

PMID- 25965138
TI  - Esophageal strictures and diverticula.
AB  - Esophageal disease and dysfunction of the lower esophageal sphincter (LES)
      manifesting as gastroesophageal reflux disease (GERD) particularly, is the most
      common of all gastrointestinal conditions impacting patients on a day-to-day
      basis. LES dysfunction can lead to anatomic changes to the distal esophagus, with
      GERD-mediated changes being benign stricture or progression of GERD to Barrett's
      esophagus and even esophageal cancer, and LES hypertension impairing esophageal
      emptying with subsequent development of pulsion esophageal diverticulum. This
      article details the causes, clinical presentation, workup, and treatment of
      esophageal stricture and epiphrenic esophageal diverticulum. Other types of
      esophageal diverticula (Zenker's and midesophageal) are also covered. 

PMID- 25965139
TI  - Foreword. Esophageal disease.

PMID- 25965140
TI  - Preface. Esophageal disease.

PMID- 25965141
TI  - Characterisation of biofilms formed by Lactobacillus plantarum WCFS1 and food
      spoilage isolates.
AB  - Lactobacillus plantarum has been associated with food spoilage in a wide range of
      products and the biofilm growth mode has been implicated as a possible source of
      contamination. In this study we analysed the biofilm forming capacity of L.
      plantarum WCFS1 and six food spoilage isolates. Biofilm formation as quantified
      by crystal violet staining and colony forming units was largely affected by the
      medium composition, growth temperature and maturation time and by strain specific
      features. All strains showed highest biofilm formation in Brain Heart Infusion
      medium supplemented with manganese and glucose. For L. plantarum biofilms the
      crystal violet (CV) assay, that is routinely used to quantify total biofilm
      formation, correlates poorly with the number of culturable cells in the biofilm.
      This can in part be explained by cell death and lysis resulting in CV stainable
      material, conceivably extracellular DNA (eDNA), contributing to the extracellular
      matrix. The strain to strain variation may in part be explained by differences in
      levels of eDNA, likely as result of differences in lysis behaviour. In line with
      this, biofilms of all strains tested, except for one spoilage isolate, were
      sensitive to DNase treatment. In addition, biofilms were highly sensitive to
      treatment with Proteinase K suggesting a role for proteins and/or proteinaceous
      material in surface colonisation. This study shows the impact of a range of
      environmental factors and enzyme treatments on biofilm formation capacity for
      selected L. plantarum isolates associated with food spoilage, and may provide
      clues for disinfection strategies in food industry. 

PMID- 25965142
TI  - Matrix Effect Compensation in Small-Molecule Profiling for an LC-TOF Platform
      Using Multicomponent Postcolumn Infusion.
AB  - The possible presence of matrix effect is one of the main concerns in liquid
      chromatography-mass spectrometry (LC-MS)-driven bioanalysis due to its impact on
      the reliability of the obtained quantitative results. Here we propose an approach
      to correct for the matrix effect in LC-MS with electrospray ionization using
      postcolumn infusion of eight internal standards (PCI-IS). We applied this
      approach to a generic ultraperformance liquid chromatography-time-of-flight
      (UHPLC-TOF) platform developed for small-molecule profiling with a main focus on
      drugs. Different urine samples were spiked with 19 drugs with different
      physicochemical properties and analyzed in order to study matrix effect (in
      absolute and relative terms). Furthermore, calibration curves for each analyte
      were constructed and quality control samples at different concentration levels
      were analyzed to check the applicability of this approach in quantitative
      analysis. The matrix effect profiles of the PCI-ISs were different: this confirms
      that the matrix effect is compound-dependent, and therefore the most suitable PCI
      IS has to be chosen for each analyte. Chromatograms were reconstructed using
      analyte and PCI-IS responses, which were used to develop an optimized method
      which compensates for variation in ionization efficiency. The approach presented
      here improved the results in terms of matrix effect dramatically. Furthermore,
      calibration curves of higher quality are obtained, dynamic range is enhanced, and
      accuracy and precision of QC samples is increased. The use of PCI-ISs is a very
      promising step toward an analytical platform free of matrix effect, which can
      make LC-MS analysis even more successful, adding a higher reliability in
      quantification to its intrinsic high sensitivity and selectivity. 

PMID- 25965143
TI  - Oxidative stress triggered by naturally occurring flavone apigenin results in
      senescence and chemotherapeutic effect in human colorectal cancer cells.
AB  - Recent studies involving phytochemical polyphenolic compounds have suggested
      flavones often exert pro-oxidative effect in vitro against wide array of cancer
      cell lines. The aim of this study was to evaluate the in-vitro pro-oxidative
      activity of apigenin, a plant based flavone against colorectal cancer cell lines
      and investigate cumulative effect on long term exposure. In the present study,
      treatment of colorectal cell lines HT-29 and HCT-15 with apigenin resulted in
      anti-proliferative and apoptotic effects characterized by biochemical and
      morphological changes, including loss of mitochondrial membrane potential which
      aided in reversing the impaired apoptotic machinery leading to negative
      implications in cancer pathogenesis. Apigenin induces rapid free radical species
      production and the level of oxidative damage was assessed by qualitative and
      quantitative estimation of biochemical markers of oxidative stress. Increased
      level of mitochondrial superoxide suggested dose dependent mitochondrial
      oxidative damage which was generated by disruption in anti-apoptotic and pro
      apoptotic protein balance. Continuous and persistent oxidative stress induced by
      apigenin at growth suppressive doses over extended treatment time period was
      observed to induce senescence which is a natural cellular mechanism to attenuate
      tumor formation. Senescence phenotype inducted by apigenin was attributed to
      changes in key molecules involved in p16-Rb and p53 independent p21 signaling
      pathways. Phosphorylation of retinoblastoma was inhibited and significant up
      regulation of p21 led to simultaneous suppression of cyclins D1 and E which
      indicated the onset of senescence. Pro-oxidative stress induced premature
      senescence mediated by apigenin makes this treatment regimen a potential
      chemopreventive strategy and an in vitro model for aging research. 

PMID- 25965144
TI  - Protection against renal ischemia-reperfusion injury in vivo by the mitochondria
      targeted antioxidant MitoQ.
AB  - Ischemia-reperfusion (IR) injury to the kidney occurs in a range of clinically
      important scenarios including hypotension, sepsis and in surgical procedures such
      as cardiac bypass surgery and kidney transplantation, leading to acute kidney
      injury (AKI). Mitochondrial oxidative damage is a significant contributor to the
      early phases of IR injury and may initiate a damaging inflammatory response. Here
      we assessed whether the mitochondria targeted antioxidant MitoQ could decrease
      oxidative damage during IR injury and thereby protect kidney function. To do this
      we exposed kidneys in mice to in vivo ischemia by bilaterally occluding the renal
      vessels followed by reperfusion for up to 24h. This caused renal dysfunction,
      measured by decreased creatinine clearance, and increased markers of oxidative
      damage. Administering MitoQ to the mice intravenously 15 min prior to ischemia
      protected the kidney from damage and dysfunction. These data indicate that
      mitochondrial oxidative damage contributes to kidney IR injury and that
      mitochondria targeted antioxidants such as MitoQ are potential therapies for
      renal dysfunction due to IR injury.

PMID- 25965145
TI  - The Glycemic Indices in Dialysis Evaluation (GIDE) study: Comparative measures of
      glycemic control in diabetic dialysis patients.
AB  - The validity of hemoglobin A1c (HgbA1c) is undergoing increasing scrutiny in the
      advanced CKD/ESRD (chronic kidney disease/end-stage renal disease) population,
      where it appears to be discordant from other glycemic indices. In the Glycemic
      Indices in Dialysis Evaluation (GIDE) Study, we sought to assess correlation of
      HgbA1c with casual glucose, glycated albumin, and serum fructosamine in a large
      group of diabetic patients on dialysis. From 26 dialysis facilities in the United
      States, 1758 diabetic patients (hemodialysis = 1476, peritoneal dialysis = 282)
      were enrolled in the first quarter of 2013. The distributions of HgbA1c and the
      other glycemic indices were analyzed. Intra-patient coefficients of variation and
      correlations among the four glycemic indices were determined. Patients with low
      HgbA1c values were both on higher erythropoietin (ESA) doses and more anemic.
      Serum glucose exhibited the highest intra-patient variability over a 3-month
      period; variability was modest among the other glycemic indices, and least with
      HgbA1c. Statistical analyses inclusive of all glycemic markers indicated modest
      to strong correlations. HgbA1c was more likely to be in the target range than
      glycated albumin or serum fructosamine, suggesting factors which may or may not
      be directly related to glycemic control, including anemia, ESA management, and
      iron administration, in interpreting HgbA1c values. These initial results from
      the GIDE Study clarify laboratory correlations among glycemic indices and add to
      concerns about reliance on HgbA1c in patients with diabetes and advanced kidney
      disease. 

PMID- 25965146
TI  - Structure and gene cluster of the O-antigen of Escherichia coli O140.
AB  - An acidic O-polysaccharide (O-antigen) was isolated from the lipopolysaccharide
      of Escherichia coli O140 and studied by sugar analysis along with 1D and 2D (1)H
      and (13)C NMR spectroscopy. The following structure of the branched
      hexasaccharide repeating unit was established: [Formula: see text]. The O-antigen
      gene cluster of E. coli O140 was sequenced. The gene functions were tentatively
      assigned by a comparison with sequences in the available databases and found to
      be in full agreement with the E. coli O140 polysaccharide structure.

PMID- 25965147
TI  - Characterising the rheology of non-Newtonian fluids using PFG-NMR and cumulant
      analysis.
AB  - Conventional rheological characterisation using nuclear magnetic resonance (NMR)
      typically utilises spatially-resolved measurements of velocity. We propose a new
      approach to rheometry using pulsed field gradient (PFG) NMR which readily extends
      the application of MR rheometry to single-axis gradient hardware. The
      quantitative use of flow propagators in this application is challenging because
      of the introduction of artefacts during Fourier transform, which arise when
      realistic sampling strategies are limited by experimental and hardware
      constraints and when particular spatial and temporal resolution are required. The
      method outlined in this paper involves the cumulant analysis of the acquisition
      data directly, thereby preventing the introduction of artefacts and reducing data
      acquisition times. A model-dependent approach is developed to enable the pipe
      flow characterisation of fluids demonstrating non-Newtonian power-law rheology,
      involving the use of an analytical expression describing the flow propagator in
      terms of the flow behaviour index. The sensitivity of this approach was
      investigated and found to be robust to the signal-to-noise ratio (SNR) and number
      of acquired data points, enabling an increase in temporal resolution defined by
      the SNR. Validation of the simulated results was provided by an experimental case
      study on shear-thinning aqueous xanthan gum solutions, whose rheology could be
      accurately characterised using a power-law model across the experimental shear
      rate range of 1-100 s(-1). The flow behaviour indices calculated using this
      approach were observed to be within 8% of those obtained using spatially-resolved
      velocity imaging and within 5% of conventional rheometry. Furthermore, it was
      shown that the number of points sampled could be reduced by a factor of 32, when
      compared to the acquisition of a volume-averaged flow propagator with 128
      gradient increments, without negatively influencing the accuracy of the
      characterisation, reducing the acquisition time to only 3% of its original value.

PMID- 25965148
TI  - Temporal dynamics in a shallow coastal benthic food web: Insights from fatty acid
      biomarkers and their stable isotopes.
AB  - We investigated the temporal variation of pelagic and benthic food sources in the
      diet of benthic taxa at a depositional site in the Southern Bight of the North
      Sea by means of fatty acid (FA) biomarkers and compound-specific stable isotope
      analysis (CSIA). The taxa were the non-selective deposit feeding nematodes
      (Sabatieria spp. and 'other nematodes'), and three dominant macrobenthic species:
      two true suspension-deposit feeders (the bivalve Abra alba and the tube dwelling
      polychaete Owenia fusiformis) and the suspected predatory mud-dwelling anemone
      Sagartia sp. These species make up on average 16% (Abra alba), 17% (Sagartia sp.)
      and 20% (Owenia fusiformis) of the biomass in the Abra alba-Kurtiella bidentata
      community in this area. Phytoplankton dynamics in the suspended particulate
      matter of the water column as inferred from cell counts, chlorophyll-a and
      organic carbon content were clearly visible in sediment and animal FA abundance
      as well, whereas phytodetritus dynamics in the sediment FA composition were less
      clear, probably due to patchy distribution or stripping of FA by macrofauna.
      Nematodes appeared to assimilate mainly Polyunsaturated Fatty Acids (PUFAs) from
      their sedimentary environment and were further non-selectively accumulating more
      (Sabatieria spp.) or less ('other nematodes') FA from the deposited
      phytodetritus. In contrast, Abra alba FA composition was consistent with a diatom
      dominated diet and consumption of Phaeocystis was observed in Owenia fusiformis,
      whereas Sagartia sp. showed evidence of a predatory behaviour. While the total FA
      content in Owenia fusiformis remained constant throughout the year, Sagartia sp.
      doubled and Abra alba increased its FA level more than 10-fold in response to the
      organic matter deposition from the phytoplankton bloom. This leads to the
      conclusion that there is no resource partitioning between non-selective deposit
      feeding nematodes and the suspension-deposit feeding macrobenthic organisms,
      suggesting they belong to separate parts of the benthic food web. 

PMID- 25965149
TI  - Temporal variation in environmental conditions and the structure of fish
      assemblages around an offshore oil platform in the North Sea.
AB  - This study reports temporal variations in the environmental conditions and the
      structure of fish assemblages observed in the vicinity of an offshore oil
      platform and the surrounding seafloor in the North Sea. Multi-seasonal sampling
      was conducted at a typical large steel jacketed facility, using mid-water fish
      traps at three different depths (i.e., 10, 50 & 100 m). Commercially important
      gadoids such as saithe Pollachius virens, haddock Melanogrammus aeglefinus and
      cod Gadus morhua were the most abundant species, however, the species composition
      and the relative abundances of the species varied with depth, season and between
      years. Comparisons with a large-scale bottom trawl survey data suggested highly
      dynamic and species-specific interactions between fish movements, changing
      environmental conditions and the physical presence of an offshore platform. Given
      the number of platforms currently installed across the North Sea, there is a need
      to identify biological mechanisms behind such dynamic interactions.

PMID- 25965150
TI  - Genotoxic potential and heart rate disorders in the Mediterranean mussel Mytilus
      galloprovincialis exposed to Superdispersant-25 and dispersed diesel oil.
AB  - The effects of ex situ exposure of Mytilus galloprovincialis to Superdispersant
      25 (S-25), diesel oil and dispersed diesel oil mixtures were studied by the
      impact on level of DNA damage in haemocytes (comet assay) and the cardiac
      activity patterns of mussels. Specimens were exposed for 72 h in a static system
      to diesel oil (100 MUL/L and 1 mL/L), S-25 (5 and 50 MUL/L), and dispersed diesel
      oil mixtures M1 (diesel oil 100 MUL/L + S-25 5 MUL/L) and M2 (diesel oil 1 mL/L +
      S-25 50 MUL/L). For positive control 40 MUM CdCl2 was used. The comet assay
      results indicated genotoxic potential of S-25 while the effects of diesel oil
      alone were not observed. The highest response was detected for M1 while the
      effects of M2 were not detected. The heart rate disorders were recorded for the
      diesel oil (1 mL/L), S-25 (50 MUL/L) and both dispersed diesel oil mixtures.

PMID- 25965152
TI  - Medicaid at 50: Marking a Milestone for Women's Health.

PMID- 25965151
TI  - From treatment to healing: the promise of trauma-informed primary care.

PMID- 25965153
TI  - The organization and delivery of family planning services in community health
      centers.
AB  - BACKGROUND: Family planning and related reproductive health services are
      essential primary care services for women. Access is limited for women with low
      incomes and those living in medically underserved areas. Little information is
      available on how federally funded health centers organize and provide family
      planning services. METHODS: This was a mixed methods study of the organization
      and delivery of family planning services in federally funded health centers
      across the United States. A national survey was developed and administered (n =
      423) and in-depth case studies were conducted of nine health centers to obtain
      detailed information on their approach to family planning. FINDINGS: Study
      findings indicate that health centers utilize a variety of organizational models
      and staffing arrangements to deliver family planning services. Health centers'
      family planning offerings are organized in one of two ways, either a separate
      service with specific providers and clinic times or fully integrated with primary
      care. Health centers experience difficulties in providing a full range of family
      planning services. MAJOR CHALLENGES: Major challenges include funding
      limitations; hiring obstetricians/gynecologists, counselors, and advanced
      practice clinicians; and connecting patients to specialized services not offered
      by the health center. CONCLUSIONS: Health centers play an integral role in
      delivering primary care and family planning services to women in medically
      underserved communities. Improving the accessibility and comprehensiveness of
      family planning services will require a combination of additional direct funding,
      technical assistance, and policies that emphasize how health centers can
      incorporate quality family planning as a fundamental element of primary care.

PMID- 25965154
TI  - Reproductive Life Plan Counseling and Effective Contraceptive Use among Urban
      Women Utilizing Title X Services.
AB  - BACKGROUND: Although the Centers for Disease Control and Prevention and the U.S.
      Office of Population Affairs recommend inclusion of reproductive life plan
      counseling (RLPC) in all well-woman health care visits, no studies have examined
      the effect of RLPC sessions on the decision to use effective contraception at
      publicly funded family planning sites. RLPC could be a particularly impactful
      intervention for disadvantaged social groups who are less likely to use the most
      effective contraceptive methods. METHODS: Using data from 771 nonpregnant, non
      pregnancy-seeking women receiving gynecological services in the Cincinnati
      Hamilton County Reproductive Health and Wellness Program, multinomial logistic
      regression models compared users of nonmedical/no method with users of 1) the
      pill, patch, or ring, 2) depot medroxyprogesterone acetate, and 3) long-acting
      reversible contraception (LARC). The effect of RLPC on the use of each form of
      contraception, and whether it mediated the effect of race/ethnicity and education
      on contraceptive use, was examined while controlling for age, insurance status,
      and birth history. The interaction between RLPC and race/ethnicity and the
      interaction between RLPC and educational attainment was also assessed. FINDINGS:
      RLPC was not associated with contraceptive use. The data suggested that RLPC may
      increase LARC use over nonmedical/no method use. RLPC did not mediate or moderate
      the effect of race/ethnicity or educational attainment on contraceptive use in
      any comparison. CONCLUSIONS: In this system of publicly funded family planning
      clinics, RLPC seems not to encourage effective method use, providing no support
      for the efficacy of the RLPC intervention. The results suggest that this
      intervention requires further development and evaluation.

PMID- 25965155
TI  - Screening Mammography Rates in the Medicare Population before and after the 2009
      U.S. Preventive Services Task Force Guideline Change: An Interrupted Time Series
      Analysis.
AB  - OBJECTIVE: We sought to examine longitudinal trends in screening mammography
      utilization and the presence of any changes in utilization associated with the
      2009 U.S. Preventive Services Task Force (USPSTF) guideline change. METHODS: We
      use 2005 through 2012 Medicare fee-for-service claims data for a 5% sample of
      randomly selected beneficiaries. The primary outcome is monthly mammography rate
      per 1,000 women. Two comparison outcomes are monthly Papanicolaou test rate and
      monthly routine eye examination rate. The statistical approach is interrupted
      time series with segmented regression analysis and nonequivalent dependent
      variables. RESULTS: Among women age 65 and 90, monthly screening mammography
      rates were significantly increasing before the 2009 USPSTF guideline change.
      Immediately after the guidelines, there was a significant drop of 1.76 per 1,000
      women (p < .001). Three years after the guideline, and after the initial
      decrease, there was no significant change in rate for those aged 65 to 74, but a
      continued and significant decline for those aged 75 and older. Two other
      preventive services (Papanicolaou test and routine eye examinations) did not show
      any shift associated with the pre- and post-guideline window. CONCLUSIONS: The
      2009 revision of USPSTF guidelines on breast cancer was associated with an
      immediate and significant decrease in screening mammography rates. The long-term
      impact of the guideline change differs by age and race and may not be fully
      quantifiable for years after its implementation.

PMID- 25965156
TI  - Sick of inequality: gender and support for paid sick days.
AB  - BACKGROUND: The availability of paid sick days (PSD) is on the forefront of
      policy issues relating to women's health and well-being. Previous research
      regarding PSD and other forms of family-work balance legislation has linked
      access to paid time off from work for addressing one's own or another's health
      concerns to a range of health benefits for working women and their families. In
      general, public support for such policies is high, but little work has tested the
      extent to which support extends to PSD. Researchers have yet to engage in a
      rigorous statistical analysis of public opinion on PSD, including whether opinion
      varies by gender. METHODS: Using data from a 2013 poll of adults in New Jersey (n
      = 925), we bridged this research gap by conducting the first multivariate
      analysis of public attitudes toward PSD. RESULTS: As expected, we found markedly
      high levels of support for PSD across all respondents, with a preponderance of
      most sociodemographic categories supporting proposed PSD legislation in New
      Jersey. We also found that gender was a strong predictor of support for PSD, with
      women significantly (odds ratio, 1.916; p <= .01) more likely than men to be in
      favor of such legislation. CONCLUSIONS: We discuss the implications of our
      findings for future work on PSD as well as for research concerning women,
      wellness, and work-life legislation more broadly.

PMID- 25965157
TI  - Effect of Gender on the Response to Hepatitis C Treatment in an Inner-City
      Population.
AB  - INTRODUCTION: Hepatitis C virus (HCV) is the leading cause of cirrhosis,
      hepatocellular carcinoma, and liver transplantation in the United States.
      Response to treatment has improved with the addition of direct acting protease
      inhibitors. However, there are limited real-world data on the role of gender in
      achieving a sustained virologic response (SVR). METHODS: We conducted a cross
      sectional study in 70 patients treated for HCV, genotype 1 infection with
      pegylated alpha interferon, ribavirin, and either telaprevir or boceprevir at our
      inner-city liver clinic. RESULTS: The SVR was significantly lower in women than
      in men (24% vs. 59%; p < .01). Statistical significance persisted after adjusting
      for age, race, genotype, prior treatment status, duration of therapy, and stage
      of fibrosis. The adjusted odds ratio for achieving SVR was significantly lower in
      women than in men (odds ratio [OR], 0.13; 95% CI, 0.03-0.58; p = .01). Relapse
      after completing treatment was more likely to occur in women (p = .02). Thirty
      four patients (48%) did not complete therapy. Discontinuation because of loss to
      follow-up was more likely in women, whereas discontinuation owing to therapy
      limiting adverse drug events were more common in men. Discontinuation rates owing
      to failure of therapy were similar in men and women. CONCLUSIONS: There was a
      significant difference in SVR between men and women. Both biological and
      nonbiological factors, the latter including access to care, adherence to therapy,
      and attitudes of and toward health care providers all could play a role in
      contributing to the observed disparity between sexes in treatment response.

PMID- 25965158
TI  - Ultra-fast Steady-State Free Precession Pulse Sequence for Fourier Decomposition
      Pulmonary MRI.
AB  - PURPOSE: To assess whether ultra-fast steady-state free precession (ufSSFP) can
      improve image quality in Fourier decomposition (FD) MRI of lung ventilation and
      perfusion. METHODS: Series of two-dimensional time-resolved lung images were
      acquired in healthy volunteers at 1.5 Tesla (T) and 3T using an FD adapted
      ufSSFP. For comparison, the imaging protocol was complemented by a standard
      implementation of the FD MRI technique using balanced steady-state free
      precession (bSSFP). Imaging parameters were evaluated to optimize the ufSSFP FD
      MRI protocol with respect to the signal intensity of the lung parenchyma and the
      severity of image artifacts. RESULTS: FD MRI with the adapted ufSSFP pulse
      sequence resulted in increased signal intensity in the lung tissue by 19% and
      significantly decreased banding artifacts due to shorter repetition times: 1.46
      ms for ufSSFP and 1.90 ms for bSSFP. Despite improved image quality FD MRI is
      still problematic at 3T. CONCLUSION: MRI of the lung with ufSSFP performs better
      than bSSFP in terms of signal and banding artifacts, and can be used to either
      increase resolution or overall image quality of FD images.

PMID- 25965159
TI  - In Situ PL and SPV Monitored Charge Carrier Injection During Metal Assisted
      Etching of Intrinsic a-Si Layers on c-Si.
AB  - Although hydrogenated amorphous silicon is already widely examined regarding its
      structural and electronic properties, the chemical etching behavior of this
      material is only roughly understood. We present a detailed study of the etching
      properties of intrinsic hydrogenated amorphous silicon, (i)a-Si:H, layers on
      crystalline silicon, c-Si, within the framework of metal assisted chemical
      etching (MACE) using silver nanoparticles (Ag NPs). The etching processes are
      examined by in situ photoluminescence (PL) and in situ surface photovoltage (SPV)
      measurements, as these techniques allow a monitoring of the hole injection that
      takes place during MACE. By in situ PL measurements and SEM images, we could
      interpret the different stages of the MACE process of (i)a-Si:H layers and
      determine etch rates of (i)a-Si:H, that are found to be influenced by the size of
      the Ag NPs. In situ PL and in situ SPV measurements both enable researchers to
      determine when the Ag NPs reach the (i)a-Si:H/c-Si interface. Furthermore, a
      preferential MACE of (i)a-Si:H versus c-Si is revealed for the first time. This
      effect could be explained by an interplay of the different thermodynamic and
      structural properties of the two materials as well as by hole injection during
      MACE resulting in a field effect passivation. The presented results allow an
      application of the examined MACE processes for Si nanostructuring applications. 

PMID- 25965160
TI  - Soil-pore water distribution of silver and gold engineered nanoparticles in
      undisturbed soils under unsaturated conditions.
AB  - Release of engineered nanoparticles (ENPs) to soil is well documented but little
      is known on the subsequent soil-pore water distribution of ENPs once present in
      soil. In this study, the availability and mobility of silver (Ag) and gold (Au)
      ENPs added to agricultural soils were assessed in two separate pot experiments.
      Pore water samples collected from pots from day 1 to 45 using porous (<0.17 MUm)
      membrane samplers suggest that both Ag and Au are retained almost completely
      within 24 h with less than 13% of the total added amount present in pore water on
      day 1. UV-Vis and TEM results showed that AuENPs in pore water were present as
      both homoaggregates and heteroaggregates until day 3 after which the
      concentration in pore water was too low to detect the presence of aggregates. A
      close relation between the concentration of Au and Fe in pore water suggests that
      the short term solubility of Au is partly controlled by natural soil colloids.
      Results suggest that under normal aerated soil conditions the actual availability
      of Ag and AuENPs is low which is relevant in view of risk assessment even though
      the impact of environmental conditions and soil properties on the reactivity of
      ENPs (and/or large ENPs aggregates) retained in the solid matrix need to be
      addressed further.

PMID- 25965161
TI  - Synthesis and protonation of an encumbered iron tetraisocyanide dianion.
AB  - Reported here are synthetic studies probing highly reduced iron centers in an
      encumbering tetraisocyano ligand environment. Treatment of FeCl2 with sodium
      amalgam in the presence of 2 equiv of the m-terphenyl isocyanide CNAr(Mes2)
      (Ar(Mes2) = 2,6-(2,4,6-Me3C6H2)2C6H3) produces the disodium tetraisocyanoferrate
      Na2[Fe(CNAr(Mes2))4]. Structural characterization of Na2[Fe(CNAr(Mes2))4]
      revealed a tight ion pair, with the Fe center adopting a tetrahedral coordination
      geometry consistent with a d(10) metal center. Attempts to disrupt the cation
      anion contacts in Na2[Fe(CNAr(Mes2))4] with cation-sequestration reagents lead to
      decomposition, except for the case of 18-crown-6, where a mononuclear complex
      featuring a dianionic 1-azabenz[b]azulene ligand was isolated in low yield.
      Formation of this 1-azabenz[b]azulene is rationalized to proceed by an aza
      Buchner ring expansion of a CNAr(Mes2) ligand mediated by a coordinatively
      unsaturated Fe center. Disodium tetraisocyanoferrate Na2[Fe(CNAr(Mes2))4] is
      readily protonated by trimethylsilanol (HOSiMe3) to produce the monohydride
      ferrate salt, Na[HFe(CNAr(Mes2))4], the anionic portion of which serves as an
      isocyano analogue of the hydrido-tetracarbonyl metalate [HFe(CO)4](-). Treatment
      of Na[HFe(CNAr(Mes2))4] with methyl triflate (MeOTf; OTf = [O3SCF3](-)) at low
      temperature in the presence of dinitrogen yields the five-coordinate Fe(0)
      complex Fe(N2)(CNAr(Mes2))4. The formation of Fe(N2)(CNAr(Mes2))4 in this
      reaction is consistent with the intermediacy of the neutral tetraisocyanide
      Fe(CNAr(Mes2))4. The decomposition of Fe(N2)(CNAr(Mes2))4 to the dimeric complex
      [Fe(eta(6)-(Mes)-MU(2)-C-CNAr(Mes))]2 and a seven-membered cyclic imine derived
      from a CNAr(Mes2) ligand is presented and provides insight into the ability of
      CNAr(Mes2) and related m-terphenyl isocyanides to stabilize zerovalent four
      coordinate iron complexes in a strongly pi-acidic ligand field. 

PMID- 25965162
TI  - Large enhancement of superconducting transition temperature of SrBi3 induced by
      Na substitution for Sr.
AB  - The Matthias rule, which is an empirical correlation between the superconducting
      transition temperature (Tc) and the average number of valence electrons per atom
      (n) in alloys and intermetallic compounds, has been used in the past as a guiding
      principle to search for new superconductors with higher Tc. The intermetallic
      compound SrBi3 (AuCu3 structure) exhibits a Tc of 5.6 K. An ab-initio electronic
      band structure calculation for SrBi3 predicted that Tc increases on decreasing
      the Fermi energy, i.e., on decreasing n, because of a steep increase in the
      density of states. In this study, we demonstrated that high-pressure (~ 3 GPa)
      and low-temperature ( < 350  degrees C) synthesis conditions enables the
      substitution of Na for about 40 at.% of Sr. With a consequent decrease in n, the
      Tc of (Sr,Na)Bi3 increases to 9.0 K. A new high-Tc peak is observed in the
      oscillatory dependence of Tc on n in compounds with the AuCu3 structure. We have
      shown that the oscillatory dependence of Tc is in good agreement with the band
      structure calculation. Our experiments reaffirm the importance of controlling the
      number of electrons in intermetallic compounds. 

PMID- 25965164
TI  - Non-genetic cancer cell plasticity and therapy-induced stemness in tumour
      relapse: 'What does not kill me strengthens me'.
AB  - Therapy resistance and tumour relapse after drug therapy are commonly explained
      by Darwinian selection of pre-existing drug-resistant, often stem-like cancer
      cells resulting from random mutations. However, the ubiquitous non-genetic
      heterogeneity and plasticity of tumour cell phenotype raises the question: are
      mutations really necessary and sufficient to promote cell phenotype changes
      during tumour progression? Cancer therapy inevitably spares some cancer cells,
      even in the absence of resistant mutants. Accumulating observations suggest that
      the non-killed, residual tumour cells actively acquire a new phenotype simply by
      exploiting their developmental potential. These surviving cells are stressed by
      the cytotoxic treatment, and owing to phenotype plasticity, exhibit a variety of
      responses. Some are pushed into nearby, latent attractor states of the gene
      regulatory network which resemble evolutionary ancient or early developmental
      gene expression programs that confer stemness and resilience. By entering such
      stem-like, stress-response states, the surviving cells strengthen their capacity
      to cope with future noxious agents. Considering non-genetic cell state dynamics
      and the relative ease with which surviving but stressed cells can be tipped into
      latent attractors provides a foundation for exploring new therapeutic approaches
      that seek not only to kill cancer cells but also to avoid promoting resistance
      and relapse that are inherently linked to the attempts to kill them. 

PMID- 25965165
TI  - Downregulation of miRNA-424: a sign of field cancerisation in clinically normal
      tongue adjacent to squamous cell carcinoma.
AB  - BACKGROUND: The overall survival for patients with squamous cell carcinoma of the
      tongue is low and the search for early diagnostic and prognostic markers is thus
      essential. MicroRNAs have been suggested as potential prognostic and diagnostic
      candidates in squamous cell carcinoma of head and neck in general. METHODS: On
      the basis of the known differences between sub-sites within the oral cavity, we
      investigated the expression and role of microRNA-424 in squamous cell carcinoma
      arising in tongue. MicroRNA levels were measured by qRT-PCR in both tissue and
      plasma samples. RESULTS: Levels of microRNA-424 were upregulated in tongue
      squamous cell carcinoma, but not in tumours originating from gingiva or floor of
      the mouth. Interestingly, microRNA-424 was downregulated in clinically normal
      tongue tissue next to tumour compared with completely healthy tongue, indicating
      that microRNA-424 could be a marker of field cancerisation in this tumour type.
      However, expression of microRNA-424 in a tongue-derived epithelial cell line
      revealed no significant changes in the expression profile of proteins and genes.
      CONCLUSIONS: Our patient data show that microRNA-424 alterations are a marker of
      field cancerisation specific for tongue tumourigenesis, which also could have a
      role in development of tongue squamous cell carcinoma.

PMID- 25965166
TI  - Response to comment on: 'evaluation of chemoresponse assays as predictive
      biomarkers'.

PMID- 25965167
TI  - Spectrophotometric determination of nitrite in soil and water using cefixime and
      central composite design.
AB  - The present paper seeks to develop a simple method for the spectrophotometric
      determination of nitrite in soil and water samples and also measure optimum
      reaction conditions along with other analytical parameters. The method is based
      on the diazotization-coupling reaction of nitrite with cefixime and 1
      naphthylamine in an acidic solution (Griess reaction). The final product that is
      an azo dye has an orange color with maximum absorption at 360 nm which Beer's Law
      is obeyed over the concentration range 0.02-15.00 mg L(-1) of nitrite. Optimal
      conditions of the variables affecting the reaction were obtained by central
      composite design (CCD). A detection limit of 4.3*10(-3) mg L(-1) was obtained for
      determination of nitrite by the proposed method. The proposed method was
      successfully applied to determine nitrite in soil and water samples. The molar
      absorptivity of the product of the reaction and RSD in determination of nitrite
      in real samples are 4.1*10(3) (L mol(-1) cm(-1)) and lower than 10%,
      respectively.

PMID- 25965168
TI  - A novel flavone-based fluorescent probe for relay recognition of HSO3(-) and
      Al(3+).
AB  - In this work, a new flavone-based fluorescent probe 3-hydroxy-3'-formylflavone
      (3HFF) was designed to achieve highly selective relay recognition of HSO3(-) and
      Al(3+) in DMSO-H2O (2:8, v/v) solution. 3HFF displayed a highly selective
      response to HSO3(-) with a green fluorescence appearing at 524 nm. Moreover, the
      in situ generated 3HFF+HSO3(-) system demonstrated eminent relay recognition
      capability for Al(3+) with a blue fluorescence appearing at 453 nm by the
      formation of a 1:1 complex between 3HFF and Al(3+) in DMSO-H2O (2:8, v/v)
      solution. However, only slight change was observed in emission intensity with
      addition of Al(3+) to 3HFF, and indicated HSO3(-) was essential for the sensing
      of Al(3+). This work achieves the detection of HSO3(-) and Al(3+) by only one
      probe and provides another example for this rare combination (anion/metal).

PMID- 25965169
TI  - Spectroscopic (FT-IR, FT-Raman, UV and NMR) investigation on 1-phenyl-2
      nitropropene by quantum computational calculations.
AB  - In this paper, the spectral analysis of 1-phenyl-2-nitropropene is carried out
      using the FTIR, FT Raman, FT NMR and UV-Vis spectra of the compound with the help
      of quantum mechanical computations using ab-initio and density functional
      theories. The FT-IR (4000-400 cm(-1)) and FT-Raman (4000-100 cm(-1)) spectra were
      recorded in solid phase, the (1)H and (13)C NMR spectra were recorded in CDCl3
      solution phase and the UV-Vis (200-800 nm) spectrum was recorded in ethanol
      solution phase. The different conformers of the compound and their minimum
      energies are studied using B3LYP functional with 6-311+G(d,p) basis set and two
      stable conformers with lowest energy were identified and the same was used for
      further computations. The computed wavenumbers from different methods are scaled
      so as to agree with the experimental values and the scaling factors are reported.
      All the modes of vibrations are assigned and the structure the molecule is
      analyzed in terms of parameters like bond length, bond angle and dihedral angle
      predicted by both B3LYP and B3PW91 methods with 6-311+G(d,p) and 6-311++G(d,p)
      basis sets. The values of dipole moment (MU), polarizability (alpha) and
      hyperpolarizability (beta) of the molecule are reported, using which the non
      linear property of the molecule is discussed. The HOMO-LUMO mappings are reported
      which reveals the different charge transfer possibilities within the molecule.
      The isotropic chemical shifts predicted for (1)H and (13)C atoms using gauge
      invariant atomic orbital (GIAO) theory show good agreement with experimental
      shifts. NBO analysis is carried out to picture the charge transfer between the
      localized bonds and lone pairs. The local reactivity of the molecule has been
      studied using the Fukui function. The thermodynamic properties (heat capacity,
      entropy and enthalpy) at different temperatures are also calculated.

PMID- 25965171
TI  - Experimental and theoretical investigation on the molecular structure,
      spectroscopic and electric properties of 2,4-dinitrodiphenylamine, 2-nitro-4
      (trifluoromethyl)aniline and 4-bromo-2-nitroaniline.
AB  - 2,4-Dinitrodiphenylamine (I), 2-nitro-4-(trifluoromethyl)aniline (II) and 4-bromo
      2-nitroaniline (III) have been investigated by DFT and experimental FTIR, Raman
      and UV-Vis spectroscopies. The gas-phase molecular geometries were consistent
      with similar compounds already reported in the literature. From the vibrational
      analysis, the main functional groups were identified and their absorption bands
      were assigned. Some differences were found between the calculated and the
      experimental UV-Vis spectra. These differences were analyzed and explained in
      terms of the TD-DFT/B3LYP limitations, which were mainly attributed to charge
      transfer (CT) effects. These findings were in agreement with previous works,
      which reported that TD-DFT/B3LYP calculations diverge from experimental results
      when the electronic transitions involve CT. Despite this, TD-DFT/B3LYP
      calculations provided satisfactory results and a detailed description of the
      electronic transitions involved in the absorption bands of the UV-Vis spectra. In
      terms of the NLO properties, it was found that compound (I) is a good candidate
      for NLO applications and deserves further study due to its good beta values.
      However, the beta values for compounds (II) and (III) were negatively affected
      compared to those found on o-nitroaniline. 

PMID- 25965170
TI  - Photophysical properties of zinc phthalocyanine-uridine single walled carbon
      nanotube--conjugates.
AB  - The photophysical properties of the conjugate of uridine and zinc mono carboxy
      phenoxy phthalocyanine (ZnMCPPc-uridine, 4) are reported in this work. The
      conjugate was also adsorbed onto single walled carbon nanotubes (ZnMCPPc-uridine
      SWCNT, 5). The X-ray photoelectron spectroscopy of 4 showed three N 1s peaks
      while that of 5 showed four N 1s peak, a new peak at 399.4 eV of 5 was assigned
      to pyrrolidonic nitrogen, due to the interaction of the pyrrolic nitrogen of 4
      with the oxygen moiety of SWCNT-COOH in 5. The triplet lifetime, triplet and
      singlet oxygen quantum yields of the zinc mono carboxy phenoxy phthalocyanine
      increased by over 40% in the presence of uridine. SWCNTs resulted in only a small
      quenching of the triplet state parameters of 4.

PMID- 25965172
TI  - Conformational state of beta-hydroxynaphthylamides: Barriers for the rotation of
      the amide group around CN bond and dynamics of the morpholine ring.
AB  - Three beta-hydroxynaphthylamides (morpholine, pyrrolidine and dimethylamine
      derivatives) have been synthesized and their conformational state was analyzed by
      NMR, X-ray and DFT calculations. In aprotic solution the molecules contain
      intramolecular OHO hydrogen bonds, which change into intermolecular ones in solid
      state. The energy barriers for the amide group rotation around the CN bond were
      estimated from the line shape analysis of (1)H and (13)C NMR signals. A tentative
      correlation between the barrier height and the strength of OHO bond was proposed.
      Calculations of the potential energy profiles for the rotations around CC and CN
      bonds were done. In case of morpholine derivative experimental indications of
      additional dynamics: chair-chair 'ring flip' in combination with the twisting
      around CC bond were obtained and confirmed by quantum chemistry calculations. 

PMID- 25965173
TI  - Synthesis of uranyl(II), vanadyl(II) and zirconyl urate complexes, spectral,
      thermal and biological studies.
AB  - Three urate chelations were obtained when uric acid was reacted with
      UO2(CH3COO)2H2O, VOSO4.XH2O and ZrOCl2.XH2O salts with neutralized with 0.1 M
      NaOH aqueous media. The 1:2 metal-to-ligand complexes [(UO2)2(C5H2N4O3)2](H2O),
      [(ZrO)2(H2O)2(C5H2N4O3)2] and [VO((C5H3N4O3)2] were characterized by elemental
      analyses, molar conductivity, (infrared, Raman and UV-vis) spectra, effective
      magnetic moment in Bohr magnetons, and thermal analysis (TG/DTG). The urate
      ligand coordinates as mononegative bidentate donor towards the mononuclear
      central vanadium atom and coordinated as binegative tetradentate mode towards the
      binuclear dioxouranium and zirconyl centers. The antibacterial activity of the
      metal complexes were tested against some kind of bacteria and fungi strains and
      compared with uric acid. The ligand, ZrO(II) and UO2(II) complex showed a week
      potential degradation on calf thymus DNA, whereas VO(II) complex slightly
      degraded the DNA.

PMID- 25965174
TI  - Rapid analysis of diesel fuel properties by near infrared reflectance spectra.
AB  - In this study, based on near infrared reflectance spectra (NIRS) of 441 samples
      from four diesel groups (-10# diesel, -20# diesel, -35# diesel, and inferior
      diesel), three spectral analysis models were established by using partial least
      square (PLS) regression for the six diesel properties (i.e., boiling point,
      cetane number, density, freezing temperature, total aromatics, and viscosity)
      respectively. In model 1, all the samples were processed as a whole; in model 2
      and model 3, samples were firstly classified into four groups by least square
      support vector machine (LS-SVM), and then partial least square regression models
      were applied to each group and each property. The main difference between model 2
      and model 3 was that the latter used the direct orthogonal signal correction
      (DOSC), which helped to get rid of the non-relevant variation in the spectra.
      Comparing these three models, two results could be concluded: (1) models for
      grouped samples had higher precision and smaller prediction error; (2) models
      with DOSC after LS-SVM classification yielded a considerable error reduction
      compared to models without DOSC. 

PMID- 25965175
TI  - SEM, EDX and Raman and infrared spectroscopic study of brianyoungite
      Zn3(CO3,SO4)(OH)4 from Esperanza Mine, Laurion District, Greece.
AB  - The mineral brianyoungite, a carbonate-sulphate of zinc, has been studied by
      scanning electron microscopy (SEM) with chemical analysis using energy dispersive
      spectroscopy (EDX) and Raman and infrared spectroscopy. Multiple carbonate
      stretching modes are observed and support the concept of non-equivalent carbonate
      units in the brianyoungite structure. Intense Raman band at 1056 cm(-1) with
      shoulder band at 1038 cm(-1) is assigned to the CO3(2-) nu1 symmetric stretching
      mode. Two intense Raman bands at 973 and 984 cm(-1) are assigned to the symmetric
      stretching modes of the SO4(2-) anion. The observation of two bands supports the
      concept of the non-equivalence of sulphate units in the brianyoungite structure.
      Raman bands at 704 and 736 cm(-1) are assigned to the CO3(2-) nu4 bending modes
      and Raman bands at 507, 528, 609 and 638 cm(-1) are assigned to the CO3(2-) nu2
      bending modes. Multiple Raman and infrared bands in the OH stretching region are
      observed, proving the existence of water and hydroxyl units in different
      molecular environments in the structure of brianyoungite. Vibrational
      spectroscopy enhances our knowledge of the molecular structure of brianyoungite.

PMID- 25965176
TI  - Rapid direct conversion of Cu(2-x)Se to CuAgSe nanoplatelets via ion exchange
      reactions at room temperature.
AB  - The use of template nanostructures for the creation of photovoltaic and
      thermoelectric semiconductors is becoming a quickly expanding synthesis strategy.
      In this work we report a simple two-step process enabling the formation of
      ternary CuAgSe nanoplatelets with a great degree of control over the composition
      and shape. Starting with hexagonal nanoplatelets of cubic Cu2-xSe, ternary CuAgSe
      nanoplatelets were generated through a rapid ion exchange reaction at 300 K using
      AgNO3 solution. The Cu2-xSe nanoplatelet template and the final CuAgSe
      nanoplatelets were analyzed by electron microscopy and X-ray diffraction (XRD).
      It was found that both the low temperature pseudotetragonal and the high
      temperature cubic forms of CuAgSe phase were created while maintaining the
      morphology of the Cu2-xSe nanoplatelet template. Thermal and electronic transport
      measurements of hot-pressed pellets of the synthesized CuAgSe nanoplatelets
      showed a drastic reduction in the thermal conductivity and a sharp transition
      from n-type (S = -45 MUV K(-1)) to p-type (S = +200 MUV K(-1)) semiconducting
      behavior upon heating above the structural transition from the low temperature
      orthorhombic to the high temperature super-ionic cubic phase. This simple
      reaction process utilizing a template nanostructure matrix represents an energy
      efficient, cost-efficient, and versatile strategy to create interesting materials
      with lower defect density and superior thermoelectric performance. 

PMID- 25965177
TI  - A distinct p53 target gene set predicts for response to the selective p53-HDM2
      inhibitor NVP-CGM097.
AB  - Biomarkers for patient selection are essential for the successful and rapid
      development of emerging targeted anti-cancer therapeutics. In this study, we
      report the discovery of a novel patient selection strategy for the p53-HDM2
      inhibitor NVP-CGM097, currently under evaluation in clinical trials. By
      intersecting high-throughput cell line sensitivity data with genomic data, we
      have identified a gene expression signature consisting of 13 up-regulated genes
      that predicts for sensitivity to NVP-CGM097 in both cell lines and in patient
      derived tumor xenograft models. Interestingly, these 13 genes are known p53
      downstream target genes, suggesting that the identified gene signature reflects
      the presence of at least a partially activated p53 pathway in NVP-CGM097
      sensitive tumors. Together, our findings provide evidence for the use of this
      newly identified predictive gene signature to refine the selection of patients
      with wild-type p53 tumors and increase the likelihood of response to treatment
      with p53-HDM2 inhibitors, such as NVP-CGM097. 

PMID- 25965178
TI  - A novel inhibitory nucleo-cortical circuit controls cerebellar Golgi cell
      activity.
AB  - The cerebellum, a crucial center for motor coordination, is composed of a cortex
      and several nuclei. The main mode of interaction between these two parts is
      considered to be formed by the inhibitory control of the nuclei by cortical
      Purkinje neurons. We now amend this view by showing that inhibitory GABA
      glycinergic neurons of the cerebellar nuclei (CN) project profusely into the
      cerebellar cortex, where they make synaptic contacts on a GABAergic subpopulation
      of cerebellar Golgi cells. These spontaneously firing Golgi cells are inhibited
      by optogenetic activation of the inhibitory nucleo-cortical fibers both in vitro
      and in vivo. Our data suggest that the CN may contribute to the functional
      recruitment of the cerebellar cortex by decreasing Golgi cell inhibition onto
      granule cells. 

PMID- 25965179
TI  - De novo synthesis of a sunscreen compound in vertebrates.
AB  - Ultraviolet-protective compounds, such as mycosporine-like amino acids (MAAs) and
      related gadusols produced by some bacteria, fungi, algae, and marine
      invertebrates, are critical for the survival of reef-building corals and other
      marine organisms exposed to high-solar irradiance. These compounds have also been
      found in marine fish, where their accumulation is thought to be of dietary or
      symbiont origin. In this study, we report the unexpected discovery that fish can
      synthesize gadusol de novo and that the analogous pathways are also present in
      amphibians, reptiles, and birds. Furthermore, we demonstrate that engineered
      yeast containing the fish genes can produce and secrete gadusol. The discovery of
      the gadusol pathway in vertebrates provides a platform for understanding its role
      in these animals, and the possibility of engineering yeast to efficiently produce
      a natural sunscreen and antioxidant presents an avenue for its large-scale
      production for possible use in pharmaceuticals and cosmetics. 

PMID- 25965180
TI  - Adhesive skin closure technique for closure of fasciotomy wounds in pediatric
      patients: a case series.
AB  - BACKGROUND: Closure of fasciotomy wounds poses a challenge, particularly in
      pediatric cardiac patients who are too high risk for general anesthesia and often
      require anticoagulant treatment. The adhesive skin closure technique enables
      wound closure without the need for a secondary procedure such as surgery
      requiring anesthesia. OBJECTIVES: This study sought to describe a treatment
      modality that assists in fasciotomy wound edge approximation without the need for
      surgery, while additionally aiding in achieving fast and aesthetic results in the
      aforementioned patient population. A case series of 4 pediatric patients with
      fasciotomy wounds is presented. MATERIALS AND METHODS: Adhesive skin closure
      strips (Steri-Strips, 3M, St. Paul, MN) were placed perpendicular to the cleansed
      wound leaving small gaps for drainage, thus achieving complete propinquity. The
      strips were replaced sequentially with new strips every 2 to 3 days. Digital
      pictures of the wounds were obtained until complete closure of the wounds was
      achieved. Outcome variables included wound closure success rates and complication
      rates including infection, bleeding, and late scar formation. RESULTS: Patient
      ages ranged from 2 weeks to 2 years, 9 months (mean: 10.5 months), average period
      of open wound prior to closure was 6.75 days (range: 5-11 days), treatment
      duration ranged from 15 to 26 days (mean: 21 days), and average follow-up was 4.5
      months. One patient died due to their primary condition. No local infections,
      wound dehiscence with the treatment regimen, or any other immediate complications
      were encountered. There was a late complication in 1 patient who presented with a
      hypertrophic scar. CONCLUSIONS: Use of the adhesive skin closure method to close
      fasciotomy wounds in pediatric patients in which surgical procedures were
      nonadvisable produced favorable results.

PMID- 25965181
TI  - Alteration of Biomechanical Properties of Skin During the Course of Healing of
      Partial-thickness Wounds.
AB  - The incidence of partial-thickness wounds is high and, until recently, little was
      known about the alteration of the biomechanical properties of the skin in these
      wounds during the course of healing. The aim of this study was to demonstrate the
      biomechanical changes in skin elasticity. MATERIALS AND METHODS: Fourteen
      standardized skin defects were created on the back of fourteen adult male Lewis
      rats (Charles River Laboratories International, Inc, Wilmington, MA) using a skin
      dermatome. Biomechanical properties of the skin were determined every 10 days
      over a period of 3 months using a skin elasticity measurement device (Cutometer
      MPA 580, Courage and Khazaka, Cologne, Germany). Calculated elasticity (UE),
      firmness of skin (R0), and overall elasticity (R8) were assessed. In addition,
      histological evaluation was performed in regard to quality of skin. RESULTS:
      After an initial decrease of UE, R0, and R8 until 30 days after surgery, the
      values of R0 and R8 increased between day 50 and day 60. Starting on day 60, a
      further decrease of values was indicated. CONCLUSION: The alteration of
      biomechanical properties of skin is a function of tissue structure. The presented
      results demonstrate the complex changes of skin biomechanical properties in the
      course of healing of partial-thickness wounds. This study could serve as a model
      to compare the effectiveness of different wound dressings in regard to skin
      elasticity.

PMID- 25965182
TI  - Pyoderma gangrenosum with common variable immunodeficiency.
AB  - Pyoderma gangrenosum (PG) is a rare ulcerative skin disease of unknown etiology.
      It can be seen on normal skin or secondary to traumas such as injections and
      biopsies. Half of reported cases are associated with systemic diseases such as
      arthritis, inflammatory bowel diseases, hematological disorders, hepatic disease,
      and necrotizing vasculitis. These lesions often occur on the trunk and
      extremities. Abscess drainage, debridement, or necrosectomy are contraindicated
      in PG, and false management of these indications aggravates the lesion. A
      diagnosis of PG is based on medical history as well as physical and laboratory
      examination according to standard criteria. Presented here is a case of a male
      patient with a medical history of recurrent abscess of injection and splenectomy
      due to splenic abscess. The patient presented with a subcutaneous abscess which
      transformed rapidly to an ulcer after abscess drainage. Consequently, the patient
      received the final diagnosis of PG with common variable immunodeficiency and was
      treated accordingly. 

PMID- 25965183
TI  - Umbilical Cord Mesenchymal Stem Cells Combined With a Collagenfibrin Double
      layered Membrane Accelerates Wound Healing.
AB  - The aim of this study was to examine the effects of human umbilical cord
      mesenchymal stem cells (hUCMSCs) in combination with a collagen-fibrin double
      layered membrane on wound healing in mice. A collagen-fibrin double-layered
      membrane was prepared, and the surface properties of the support material were
      investigated using a scanning electron microscope. Twenty-four mice were prepared
      for use as full-thickness skin wound models and randomly divided into 3 groups:
      group A, a control group in which the wounds were bound using a conventional
      method; group B, a group treated with hUCMSCs combined with a collagen membrane;
      and group C, a group treated with hUCMSCs combined with a collagen-fibrin double
      layered membrane. The postoperative concrescence of the wounds was observed daily
      to evaluate the effects of the different treatments. Scanning electron microscope
      observation showed the collagen-fibrin scaffolds exhibited a highly porous and
      interconnected structure, and wound healing in the double-layered membrane group
      was better than in groups A or B. Treatment with hUCMSCs combined with a collagen
      fibrin double-layered membrane accelerated wound healing. 

PMID- 25965184
TI  - Editorial message: The power of one.

PMID- 25965186
TI  - Thermodynamics of Associated Electrolytes in Water: Molecular Dynamics
      Simulations of Sulfate Solutions.
AB  - A polarizable force field for the sulfate anion SO4(2-) has been developed and
      extended from nonpolarizable force fields in order to reproduce its structural
      and thermodynamics properties in aqueous solution. Two force fields with
      different atomic partial charges on S and O have been tested and used with
      molecular dynamics with explicit polarization. The results obtained with our
      developed force field are in good agreement with the experimental hydration
      properties of the sulfate anion. In addition to molecular dynamics simulations of
      the sulfate anion in aqueous solution, potentials of mean force of sulfate
      electrolytes have been calculated via umbrella-sampling molecular dynamics
      simulations, i.e., MgSO4, EuSO4(+), and UO2SO4. These potentials allow for
      calculating pair association constants directly comparable to the experimental
      ones. In the case of monoatomic cations such as Mg(2+) and Eu(3+), the
      association constants calculated are in very good agreement with the experimental
      values, i.e., pKcalc = 2.21 (vs 2.21 experimentally) and 3.86 (vs 3.56-3.78
      experimentally) for MgSO4 and EuSO4(+), respectively. In the case of purely
      molecular electrolyte (UO2SO4), the association constant calculated (pKcalc =
      1.58-2.07) is in agreement with the range of values available in the literature
      (pKexp = 1.17-3.14).

PMID- 25965185
TI  - Changing patterns of the temperature-mortality association by time and location
      in the US, and implications for climate change.
AB  - The shape of the non-linear relationship between temperature and mortality varies
      among cities with different climatic conditions. There has been little
      examination of how these curves change over space and time. We evaluated the
      short-term effects of hot and cold temperatures on daily mortality over six 7
      year periods in 211 US cities, comprising over 42 million deaths. Cluster
      analysis was used to group the cities according to similar temperatures and
      relative humidity. Temperature-mortality functions were calculated using B
      splines to model the heat effect (lag 0) and the cold effect on mortality (moving
      average lags 1-5). The functions were then combined through meta-smoothing and
      subsequently analyzed by meta-regression. We identified eight clusters. At lag 0,
      Cluster 5 (West Coast) had a RR of 1.14 (95% CI: 1.11,1.17) for temperatures of
      27  degrees C vs 15.6  degrees C, and Cluster 6 (Gulf Coast) has a RR of 1.04
      (95% CI: 1.03,1.05), suggesting that people are acclimated to their respective
      climates. Controlling for cluster effect in the multivariate-meta regression we
      found that across the US, the excess mortality from a 24-h temperature of 27 
      degrees C decreased over time from 10.6% to 0.9%. We found that the overall risk
      due to the heat effect is significantly affected by summer temperature mean and
      air condition usage, which could be a potential predictor in building climate
      change scenarios.

PMID- 25965187
TI  - Upconverting-nanoparticle-assisted photochemistry induced by low-intensity near
      infrared light: how low can we go?
AB  - Upconverting nanoparticles (UCNPs) convert near-infrared (NIR) light into UV or
      visible light that can trigger photoreactions of photosensitive compounds. In
      this paper, we demonstrate how to reduce the intensity of NIR light for UCNP
      assisted photochemistry. We synthesized two types of UCNPs with different
      emission bands and five photosensitive compounds with different absorption bands.
      A lambda=974 nm laser was used to induce photoreactions in all of the
      investigated photosensitive compounds in the presence of the UCNPs. The
      excitation thresholds of the photoreactions induced by lambda=974 nm light were
      measured. The lowest threshold was 0.5 W cm(-2) , which is lower than the maximum
      permissible exposure of skin (0.726 W cm(-2) ). We demonstrate that low-intensity
      NIR light can induce photoreactions after passing through a piece of tissue
      without damaging the tissue. Our results indicate that the threshold for UCNP-
      assisted photochemistry can be reduced by using highly photosensitive compounds
      that absorb upconverted visible light. Low excitation intensity in UCNP-assisted
      photochemistry is important for biomedical applications because it minimizes the
      overheating problems of NIR light and causes less photodamage to biomaterials. 

PMID- 25965188
TI  - 2D Inorganic-Antimalarial Drug-Polymer Hybrid with pH-Responsive Solubility.
AB  - Artesunic acid (ASH), an antimalarial drug, has low oral bioavailability due to
      its low aqueous solubility. To overcome this problem, artesunate (AS) was
      intercalated into zinc basic salt (ZBS) via co-precipitation. AS was immobilized
      with a tilted double layer arrangement, which was also confirmed by XRD and 1-D
      electron density mapping. In order to decrease the release rate of AS under
      gastrointestinal conditions and to simultaneously increase the release rate of AS
      under intestinal conditions, ZBS-AS was coated with EUDRAGIT L100 (ZBS-AS-L100).
      Finally, we performed an in-vivo pharmacokinetic study to compare the oral
      bioavailability of AS of ZBS-AS-L100 with that of ASH. Surprisingly, it was found
      that the former is 5.5 times greater than the latter due to an enhanced
      solubility of AS thanks to the ternary hybridization with ZBS and EUDRAGIT L100.
      Therefore, the present ZBS-AS-L100 system has a great potential as a novel
      antimalarial drug formulation with pH selectivity and enhanced bioavailability. 

PMID- 25965189
TI  - Vacuum Casimir energy densities and field divergences at boundaries.
AB  - We consider and review the emergence of singular field fluctuations or energy
      densities at sharp boundaries or point-like field sources in the vacuum. The
      presence of singular energy densities of a field may be relevant from a
      conceptual point of view, because they contribute to the self-energy of the
      system. They could also generate significant gravitational effects. We first
      consider the case of the interface between a metallic boundary and the vacuum,
      and obtain the structure of the singular electric and magnetic energy densities
      at the interface through an appropriate limit from a dielectric to an ideal
      conductor. Then, we consider the case of a nondispersive and nondissipative point
      like source of the electromagnetic field, described by its polarizability, and
      show that also in this case the electric and magnetic energy densities show a
      singular structure at the source position. We discuss how, in both cases, these
      singularities give an essential contribution to the electromagnetic self-energy
      of the system; moreover, they solve an apparent inconsistency between the space
      integral of the field energy density and the average value of the field
      Hamiltonian. The singular behavior we find is softened, or even eliminated, for
      boundaries fluctuating in space and for extended field sources. We discuss in
      detail the case in which a reflecting boundary is not fixed in space but is
      allowed to move around an equilibrium position, under the effect of quantum
      fluctuations of its position. Specifically, we consider the simple case of a 1D
      massless scalar field in a cavity with one fixed and one mobile wall described
      quantum-mechanically. We investigate how the possible motion of the wall changes
      the vacuum fluctuations and the energy density of the field, compared with the
      fixed-wall case. Also, we explicitly show how the fluctuating motion of the wall
      smears out the singular behaviour of the field energy density at the boundary. 

PMID- 25965190
TI  - Air pollution and daily clinic visits for migraine in a subtropical city: Taipei,
      Taiwan.
AB  - This study was undertaken to determine whether there was an association between
      air pollutant levels and daily clinic visits for migraine in Taipei, Taiwan.
      Daily clinic visits for migraine and ambient air pollution data for Taipei were
      obtained for the period 2006-2011. The relative risk of clinic visits for
      migraine was estimated using a case-crossover approach, controlling for weather
      variables, day of the week, seasonality, and long-term time trends. In the single
      pollutant models, on warm days (>23 degrees C) statistically significant positive
      associations were found for increased rate of migraine occurrence and levels of
      particulate matter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon
      monoxide (CO), and ozone (O3). On cool days (<23 degrees C), all pollutants were
      significantly associated with increased migraine visits except CO and SO2. For
      the two-pollutant models, O3 and NO2 were significant for higher rate of migraine
      visits in combination with each of the other four pollutants on cool days. On
      warm days, CO remained statistically significant in all two-pollutant models.
      This study provides evidence that higher levels of ambient air pollutants enhance
      the risk of clinic visits for migraine. 

PMID- 25965191
TI  - Exploring the potential interference of estuarine sediment contaminants with the
      DNA repair capacity of human hepatoma cells.
AB  - Estuaries may be reservoirs of a wide variety of pollutants, including mutagenic
      and carcinogenic substances that may impact on the ecosystem and human health. A
      previous study showed that exposure of human hepatoma (HepG2) cells to extracts
      from sediment samples collected in two areas (urban/industrial and
      riverine/agricultural) of an impacted estuary (Sado, Portugal), produced
      differential cytotoxic and genotoxic effects. Those effects were found to be
      consistent with levels and nature of sediment contamination. The present study
      aimed at evaluating whether the mixtures of contaminants contained in those
      extracts were able to modulate DNA repair capacity of HepG2 cells. The residual
      level of DNA damage was measured by the comet assay in cells exposed for 24 or 48
      h to different extracts, after a short preexposure to a challenging concentration
      range of ethyl methanesulfonate (EMS), as a model alkylating agent. The results
      suggested that the mixture of contaminants present in the tested samples, besides
      a potential direct effect on the DNA molecule, may also interfere with DNA repair
      mechanisms in HepG2 cells, thus impairing their ability to deal with genotoxic
      stress and, possibly, facilitating accumulation of mutations. Humans are
      environmentally/occupationally exposed to mixtures rather than to single
      chemicals. Thus, the observation that estuarine contaminants induce direct and
      indirect DNA strand breakage in human cells, the latter through the impairment of
      DNA repair, raises additional concerns regarding potential hazards from exposure
      and the need to further explore these endpoints in the context of environmental
      risk assessment. 

PMID- 25965192
TI  - Antivibration gloves: effects on vascular and sensorineural function, an animal
      model.
AB  - Anti-vibration gloves have been used to block the transmission of vibration from
      powered hand tools to the user, and to protect users from the negative health
      consequences associated with exposure to vibration. However, there are
      conflicting reports as to the efficacy of gloves in protecting workers. The goal
      of this study was to use a characterized animal model of vibration-induced
      peripheral vascular and nerve injury to determine whether antivibration materials
      reduced or inhibited the effects of vibration on these physiological symptoms.
      Rats were exposed to 4 h of tail vibration at 125 Hz with an acceleration 49
      m/s(2). The platform was either bare or covered with antivibrating glove
      material. Rats were tested for tactile sensitivity to applied pressure before and
      after vibration exposure. One day following the exposure, ventral tail arteries
      were assessed for sensitivity to vasodilating and vasoconstricting factors and
      nerves were examined histologically for early indicators of edema and
      inflammation. Ventral tail artery responses to an alpha2C-adrenoreceptor agonist
      were enhanced in arteries from vibration-exposed rats compared to controls,
      regardless of whether antivibration materials were used or not. Rats exposed to
      vibration were also less sensitive to pressure after exposure. These findings are
      consistent with experimental findings in humans suggesting that antivibration
      gloves may not provide protection against the adverse health consequences of
      vibration exposure in all conditions. Additional studies need to be done
      examining newer antivibration materials. 

PMID- 25965193
TI  - Differential response of human nasal and bronchial epithelial cells upon exposure
      to size-fractionated dairy dust.
AB  - Exposure to organic dusts is associated with increased respiratory morbidity and
      mortality in agricultural workers. Organic dusts in dairy farm environments are
      complex, polydisperse mixtures of toxic and immunogenic compounds. Previous
      toxicological studies focused primarily on exposures to the respirable size
      fraction; however, organic dusts in dairy farm environments are known to contain
      larger particles. Given the size distribution of dusts from dairy farm
      environments, the nasal and bronchial epithelia represent targets of agricultural
      dust exposures. In this study, well-differentiated normal human bronchial
      epithelial cells and human nasal epithelial cells were exposed to two different
      size fractions (PM10 and PM>10) of dairy parlor dust using a novel aerosol-to
      cell exposure system. Levels of proinflammatory transcripts (interleukin [IL]-8,
      IL-6, and tumor necrosis factor [TNF]-alpha) were measured 2 h after exposure.
      Lactate dehydrogenase (LDH) release was also measured as an indicator of
      cytotoxicity. Cell exposure to dust was measured in each size fraction as a
      function of mass, endotoxin, and muramic acid levels. To our knowledge, this is
      the first study to evaluate the effects of distinct size fractions of
      agricultural dust on human airway epithelial cells. Our results suggest that both
      PM10 and PM>10 size fractions elicit a proinflammatory response in airway
      epithelial cells and that the entire inhalable size fraction needs to be
      considered when assessing potential risks from exposure to agricultural dusts.
      Further, data suggest that human bronchial cells respond differently to these
      dusts than human nasal cells, and therefore that the two cell types need to be
      considered separately in airway cell models of agricultural dust toxicity. 

PMID- 25965194
TI  - Effect of Providing Information on Students' Knowledge and Concerns about
      Hydraulic Fracking.
AB  - Governmental agencies, regulators, health professionals, and the public are faced
      with understanding and responding to new development practices and conditions in
      their local and regional environment. While hydraulic fracking (fracking) for
      shale gas has been practiced for over 50 years in some states, it is a relatively
      recent event in the northeastern United States. Providing environmental health
      information to the public about fracking requires understanding both the
      knowledge base and the perceptions of the public. The knowledge, perceptions, and
      concerns of college students about fracking were examined. Students were
      interviewed at Rutgers University in New Jersey, a state without any fracking,
      although fracking occurs in nearby Pennsylvania. Objectives were to determine (1)
      knowledge about fracking, (2) rating of concerns, (3) trusted information
      sources, (4) importance of fracking relative to other energy sources, and (5) the
      effect of a 15-min lecture and discussion on these aspects. On the second survey,
      students improved on their knowledge (except the components used for fracking),
      and their ratings changed for some concerns, perceived benefits, and trusted
      information sources. There was no change in support for further development of
      natural gas, but support for solar, wind, and wave energy decreased. Data suggest
      that students' knowledge and perceptions change with exposure to information, but
      many of these changes were due to students using the Internet to look up
      information immediately after the initial survey and lecture. Class discussions
      indicated a general lack of trust for several information sources available on
      the Web. 

PMID- 25965195
TI  - Effects of a mixture of pesticides on the adult female reproductive system of
      Sprague-Dawley, Wistar, and Lewis rats.
AB  - The Brazilian federal government Agency for Health Surveillance detected
      pesticide residues in fresh food available for consumers all over the country.
      The current study investigated the effects of a mixture of some of those
      pesticides (dichlorvos, dicofol, dieldrin, endosulfan, and permethrin) on the
      reproductive system of Sprague-Dawley (SD), Wistar (WT), and Lewis (LEW) rats.
      Female rats from each strain were randomized into three experimental groups and
      were fed a control diet or diets added with pesticides mixture at their
      respective no-observed-effect level (NOEL)/no-observed-adverse-effect level
      (NOAEL) (low dose) (mg/kg/d): dichlorvos (0.23), dicofol (0.5), dieldrin (0.025),
      endosulfan (0.7), permethrin (5), or lowest-observed-effect level (LOEL)/lowest
      effect level (LEL)/ lowest-observed-adverse-effect level (LOAEL) (toxically
      effective dose) (mg/kg/d): dichlorvos (2.3), dicofol (2.1), dieldrin (0.05),
      endosulfan (3.8), and permethrin (25) as reported in the literature. Euthanasia
      was performed between wk 10 and 12, during the estrous stage. Decreased body
      weights gain (SD and WT) and increased liver weights (SD, WT, and LEW) were
      observed in each strain fed the pesticides mixture at the higher levels. At that
      dose level, rat strains also varied in their responses regarding the estrous
      cycle, hormonal levels, and number of developing ovarian follicles. The studied
      mixture of pesticides was found to interfere with the female reproductive system
      when individual pesticides were mixed above a certain level, indicating a
      threshold exists for each of the strains studied. 

PMID- 25965196
TI  - Prediction of Protein Structure by Template-Based Modeling Combined with the
      UNRES Force Field.
AB  - A new approach to the prediction of protein structures that uses distance and
      backbone virtual-bond dihedral angle restraints derived from template-based
      models and simulations with the united residue (UNRES) force field is proposed.
      The approach combines the accuracy and reliability of template-based methods for
      the segments of the target sequence with high similarity to those having known
      structures with the ability of UNRES to pack the domains correctly. Multiplexed
      replica-exchange molecular dynamics with restraints derived from template-based
      models of a given target, in which each restraint is weighted according to the
      accuracy of the prediction of the corresponding section of the molecule, is used
      to search the conformational space, and the weighted histogram analysis method
      and cluster analysis are applied to determine the families of the most probable
      conformations, from which candidate predictions are selected. To test the
      capability of the method to recover template-based models from restraints, five
      single-domain proteins with structures that have been well-predicted by template
      based methods were used; it was found that the resulting structures were of the
      same quality as the best of the original models. To assess whether the new
      approach can improve template-based predictions with incorrectly predicted domain
      packing, four such targets were selected from the CASP10 targets; for three of
      them the new approach resulted in significantly better predictions compared with
      the original template-based models. The new approach can be used to predict the
      structures of proteins for which good templates can be found for sections of the
      sequence or an overall good template can be found for the entire sequence but the
      prediction quality is remarkably weaker in putative domain-linker regions. 

PMID- 25965197
TI  - Differentiation of C57/BL6 mice bone marrow mononuclear cells into early
      endothelial progenitors cells in different culture conditions.
AB  - Endothelial progenitor cells (EPCs) can be isolated from bone marrow and
      characterized by the expression of cellular markers such as CD34, CD133, VEGFR2,
      CD31, and VE-Cadherin, by the uptake of acetylated low-density lipoprotein and by
      in vitro tube formation in tridimensional matrices. These cells are able to
      differentiate into mature endothelial cells and participate in the re
      endothelization of damaged vessels. In this work, we tested different cultured
      media that can promote the proliferation and differentiation of mononuclear cells
      (MNCs) into early EPCs, with defined concentrations of growth factors and serum
      in order to establish a composition that may ensure us the reproducibility of our
      cultures. MNCs from mice bone marrow were cultivated using selective culture
      media containing DMEM or M199 supplemented with 10% FBS, VEGF, bFGF, and IGF, for
      3, 7, and 14 days. Differentiation into early EPCs was analyzed using
      immunohistochemistry, FACS and western blotting and by functional parameters as
      uptake of ac-LDL, and formation of vessel-like structures. The cells cultivated
      with medium DMEM-M1 (DMEM plus VEGF, bFGF and IGF) expressed CD34, CD133, CD31,
      VEGFR2, and VE-Cadherin at all culture time-points with increased expression of
      these markers after 7 days. Only EPCs cultured for 30 days were able to form
      vessel-like structure. The uptake of ac-LDL was observed after 3, 7, 14, and 30
      days, confirming the differentiation of mononuclear cells into early EPCs. DMEM
      M1 was able to sustain MNCs proliferation and differentiation, increasing the
      expression of the characteristic EPC markers, allowing the expansion of early
      EPCs in culture in a similar way to that observed in commercial available media. 

PMID- 25965201
TI  - Untitled (bouquet of flowers): Elizabeth Sprague.

PMID- 25965198
TI  - Epigenetic Regulation of Tolerance to Toll-Like Receptor Ligands in Alveolar
      Epithelial Cells.
AB  - To protect the host against exuberant inflammation and injury responses, cells
      have the ability to become hyporesponsive or "tolerized" to repeated stimulation
      by microbial and nonmicrobial insults. The lung airspace is constantly exposed to
      a variety of exogenous and endogenous Toll-like receptor (TLR) ligands, yet the
      ability of alveolar epithelial cells (AECs) to be tolerized has yet to be
      examined. We hypothesize that type II AECs will develop a tolerance phenotype
      upon repeated TLR agonist exposure. To test this hypothesis, primary AECs
      isolated from the lungs of mice and a murine AEC cell line (MLE-12) were
      stimulated with either a vehicle control or a TLR ligand for 18 hours, washed,
      then restimulated with either vehicle or TLR ligand for an additional 6 hours.
      Tolerance was assessed by measurement of TLR ligand-stimulated chemokine
      production (monocyte chemoattractant protein [MCP]-1/CCL2, keratinocyte
      chemoattractant [KC]/CXCL1, and macrophage inflammatory protein [MIP]-2/CXCL2).
      Sequential treatment of primary AECs or MLE-12 cells with TLR agonists resulted
      in induction of either tolerance or cross-tolerance. The induction of tolerance
      was not due to expression of specific negative regulators of TLR signaling
      (interleukin-1 receptor associated kinase [IRAK]-M, Toll-interacting protein
      [Tollip], single Ig IL-1-related receptor [SIGIRR], or suppressor of cytokine
      signaling [SOCS]), inhibitory microRNAs (miRs; specifically, miR-155 and
      miR146a), or secretion of inhibitory or regulatory soluble mediators
      (prostaglandin E2, IL-10, transforming growth factor-beta, or IFN-alpha/beta).
      Moreover, inhibition of histone demethylation or DNA methylation did not prevent
      the development of tolerance. However, treatment of AECs with the histone
      deacetylase inhibitors trichostatin A or suberoylanilide hyrozamine resulted in
      reversal of the tolerance phenotype. These findings indicate a novel mechanism by
      which epigenetic modification regulates the induction of tolerance in AECs. 

PMID- 25965202
TI  - Everything you ever wanted to know about evidence-based medicine.

PMID- 25965203
TI  - Of SCOTUS and chicken.

PMID- 25965210
TI  - Ensuring competency and professionalism through state medical licensing.

PMID- 25965211
TI  - Professionalism, self-regulation, and motivation: how did health care get this so
      wrong?

PMID- 25965212
TI  - Aiming higher to enhance professionalism: beyond accreditation and certification.

PMID- 25965213
TI  - Undergraduate medical education and the foundation of physician professionalism.

PMID- 25965214
TI  - Enhancing professionalism through management.

PMID- 25965215
TI  - Professionalism and its implications for governance and accountability of
      graduate medical education in the United States.

PMID- 25965216
TI  - Postgraduate education of physicians: professional self-regulation and external
      accountability.

PMID- 25965217
TI  - Of the profession, by the profession, and for patients, families, and
      communities: ABMS board certification and medicine's professional self
      regulation.

PMID- 25965218
TI  - Professional self-regulation in a changing world: old problems need new
      approaches.

PMID- 25965219
TI  - The role of maintenance of certification programs in governance and
      professionalism.

PMID- 25965220
TI  - Medicine's continuous improvement imperative.

PMID- 25965221
TI  - Reforming the continuing medical education system.

PMID- 25965222
TI  - Redesigning metrics to integrate professionalism into the governance of health
      care.

PMID- 25965223
TI  - Physician professionalism in employed practice.

PMID- 25965224
TI  - Professionalism, fiduciary duty, and health-related business leadership.

PMID- 25965225
TI  - The transformation of US physicians.

PMID- 25965226
TI  - Governance and professionalism in medicine: a UK perspective.

PMID- 25965227
TI  - Maintaining physician competence and professionalism: Canada's fine balance.

PMID- 25965228
TI  - Medical professionalism and the future of public trust in physicians.

PMID- 25965229
TI  - A piece of my mind: Back to the heart of the matter.

PMID- 25965230
TI  - Professionalism, governance, and self-regulation of medicine.

PMID- 25965231
TI  - Medical professionalism.

PMID- 25965232
TI  - Tasking the "self" in the self-governance of medicine.

PMID- 25965233
TI  - Achalasia: a systematic review.
AB  - IMPORTANCE: Achalasia significantly affects patients' quality of life and can be
      difficult to diagnose and treat. OBJECTIVE: To review the diagnosis and
      management of achalasia, with a focus on phenotypic classification pertinent to
      therapeutic outcomes. EVIDENCE REVIEW: Literature review and MEDLINE search of
      articles from January 2004 to February 2015. A total of 93 articles were included
      in the final literature review addressing facets of achalasia epidemiology,
      pathophysiology, diagnosis, treatment, and outcomes. Nine randomized controlled
      trials focusing on endoscopic or surgical therapy for achalasia were included
      (734 total patients). FINDINGS: A diagnosis of achalasia should be considered
      when patients present with dysphagia, chest pain, and refractory reflux symptoms
      after an endoscopy does not reveal a mechanical obstruction or an inflammatory
      cause of esophageal symptoms. Manometry should be performed if achalasia is
      suspected. Randomized controlled trials support treatments focused on disrupting
      the lower esophageal sphincter with pneumatic dilation (70%-90% effective) or
      laparoscopic myotomy (88%-95% effective). Patients with achalasia have a variable
      prognosis after endoscopic or surgical myotomy based on subtypes, with type II
      (absent peristalsis with abnormal pan-esophageal high-pressure patterns) having a
      very favorable outcome (96%) and type I (absent peristalsis without abnormal
      pressure) having an intermediate prognosis (81%) that is inversely associated
      with the degree of esophageal dilatation. In contrast, type III (absent
      peristalsis with distal esophageal spastic contractions) is a spastic variant
      with less favorable outcomes (66%) after treatment of the lower esophageal
      sphincter. CONCLUSIONS AND RELEVANCE: Achalasia should be considered when
      dysphagia is present and not explained by an obstruction or inflammatory process.
      Responses to treatment vary based on which achalasia subtype is present.

PMID- 25965234
TI  - Hoarseness and laryngopharyngeal reflux.

PMID- 25965235
TI  - Screening for hepatitis C.

PMID- 25965236
TI  - A 4-drug combination (Viekira Pak) for hepatitis C.

PMID- 25965237
TI  - Association between regulatory advisories and codeine prescribing to postpartum
      women.

PMID- 25965238
TI  - Chlorhexidine bathing and infections in critically ill patients.

PMID- 25965239
TI  - Chlorhexidine bathing and infections in critically ill patients.

PMID- 25965240
TI  - Chlorhexidine bathing and infections in critically ill patients--reply.

PMID- 25965241
TI  - Use of wearable monitoring devices to change health behavior.

PMID- 25965242
TI  - Use of wearable monitoring devices to change health behavior.

PMID- 25965243
TI  - Use of wearable monitoring devices to change health behavior--reply.

PMID- 25965245
TI  - The care of the patient.

PMID- 25965246
TI  - JAMA patient patient: Achalasia.

PMID- 25965247
TI  - Metal-free, regio- and stereoselective synthesis of linear (E)-allylic compounds
      using C, N, O, and S nucleophiles.
AB  - A variety of allylic acetates and derivatives were synthesized by an efficient
      two-step protocol that employs readily available terminal alkenes as starting
      materials. This method is highly regio- and stereoselective, affording the linear
      (E)- isomer as the sole adduct. This process tolerates several functional groups
      including halogen-containing molecules, and it is general for weak oxygen,
      carbon, nitrogen, and sulfur nucleophiles. Furthermore, adducts were obtained in
      good to excellent yields. 

PMID- 25965248
TI  - Effect of oil droplet size on activation energy for coalescence of oil droplets
      in an O/W emulsion.
AB  - The activation energy of a reasonable order of magnitude was estimated for the
      coalescence of oil droplets in an O/W emulsion by formulating the balance of
      forces acting on a droplet that crosses over the potential barrier to coalesce
      with another droplet by the DLVO theory and Stokes' law. An emulsion with smaller
      oil droplets was shown to be more stable. 

PMID- 25965249
TI  - A comparison of referral patterns to a multispecialty eConsultation service
      between nurse practitioners and family physicians: The case for eConsult.
AB  - PURPOSE: To explore referral patterns of nurse practitioners (NPs) and family
      physicians (FPs) using an electronic consultation (eConsult) service, and assess
      their perspectives on the service's value to their patients and themselves. DATA
      SOURCES: A mixed methods study including a cross-sectional analysis of
      utilization data drawn from all eConsults completed from April 15, 2011 to
      September 30, 2014, and a content analysis of NP survey responses completed from
      January 1 to September 30, 2014. CONCLUSIONS: A total of 4260 eConsults were
      included in the cross-sectional analysis (3686 from FPs and 574 from NPs). In our
      sample, NPs directed more cases to dermatology and fewer cases to cardiology and
      neurology (p < .0001) than did FPs, and were more likely to report that an
      eConsult led to new advice for a new or additional course of action (62.8% vs.
      57.5%) and less likely to report it resulted in an avoided referral (35.5% vs.
      41.8%, p = .005). NPs reported slightly higher levels of perceived value of
      eConsults for their patients and themselves. IMPLICATIONS FOR PRACTICE:
      Differences in use and impact of eConsult exist between NPs and FPs. NPs value
      the service highly for their patients and themselves. The service reduces
      potential inequities related to outdated payment and scope of practice policies.

PMID- 25965250
TI  - HBeAg-negative chronic hepatitis patients should be monitored more strictly: a
      cross-sectional retrospective study on antiviral treatment-naive patients.
AB  - AIM: To investigate the prevalence and characteristics of hepatitis B e antigen
      (HBeAg) negative/treatment naive subjects with low hepatitis B virus (HBV) DNA
      levels (<10(4)  copies/ml) and low alanine aminotransferase (ALT) levels (<2 *
      upper limit of normal) in patients with HBV-related hepatocellular carcinoma
      (HCC). METHODS: A total of 226 treatment naive patients diagnosed with HBV
      related HCC, divided into five Barcelona Clinic Liver Cancer (BCLC) stages, were
      enrolled and retrospectively analyzed. Virological parameters including hepatitis
      B surface antigen (HBsAg), HBeAg, HBV DNA levels, and laboratory parameters
      including ALT and aspartame aminotransferase were accessed at the time of HCC was
      diagnosed. Comparison between HBeAg positive patients and HBeAg negative patients
      was performed using a chi(2) test. RESULTS: While laboratory parameters
      correlated with BCLC stages, virological parameters did not. HBeAg negative
      patients were more prevalent than HBeAg positive patients (160, 70.8% vs. 66,
      29.2%). HBsAg and HBV DNA levels in HBeAg negative patients were significantly
      lower than that in HBeAg positive patients (all P < 0.001). Of the 160 HBeAg
      negative patients, 74 (46.25%) had low HBsAg, 76 (47.5%) had low DNA levels, and
      35 (21.9%) patients had low DNA and normal ALT levels. CONCLUSIONS: In treatment
      naive patients with HBV-related HCC, the majority (70.8%) were HBeAg negative
      patients. More than one fifth of HBeAg negative patients had low HBV DNA levels
      and normal ALT levels, indicating more strict monitoring for HBeAg negative
      patients is needed.

PMID- 25965251
TI  - Recent advances in polyoxometalate-catalyzed reactions.

PMID- 25965252
TI  - Effect of pH and retention time on volatile fatty acids production during mixed
      culture fermentation.
AB  - Mixed culture fermentation consists of stable microbial population hence waste
      could be potentially used as a substrates. The aim of the work was to investigate
      the impact of pH and retention time on the anaerobic mixed culture fermentation.
      Trials at different pH (4-12) in unbuffered systems were conducted for 5, 10 and
      15days. The highest VFAs concentration was achieved after 15days at pH 10
      (0.62g/gVSadded), promising results were also achieved for pH 11
      (0.54g/gVSadded). For pH 4 and short retention time propionic acid was the major
      product instead of acetic acid. For batches run at 15days (besides pH 6) caproic
      acid presence was noticed whereas at pH 11 occurrence of succinic was quantified.
      Significant correlation between operational factors and fermentation's effluents
      was proved. Throughout changing simple operating parameters one could design
      process to produce desirable concentration and composition of VFAs. 

PMID- 25965253
TI  - A whole biodiesel conversion process combining isolation, cultivation and in situ
      supercritical methanol transesterification of native microalgae.
AB  - A coupled process combining microalgae production with direct supercritical
      biodiesel conversion using a reduced number of operating steps is proposed in
      this work. Two newly isolated native microalgae strains, identified as Chlorella
      sp. and Nannochloris sp., were cultivated in both batch and continuous modes.
      Maximum productivities were achieved during continuous cultures with 318mg/lday
      and 256mg/lday for Chlorella sp. and Nannochloris sp., respectively. Microalgae
      were further characterized by determining their photosynthetic performance and
      nutrient removal efficiency. Biodiesel was produced by catalyst-free in situ
      supercritical methanol transesterification of wet unwashed algal biomass (75wt.%
      of moisture). Maximum biodiesel yields of 45.62wt.% and 21.79wt.% were reached
      for Chlorella sp. and Nannochloris sp., respectively. The analysis of
      polyunsaturated fatty acids of Chlorella sp. showed a decrease in their
      proportion when comparing conventional and supercritical transesterification
      processes (from 37.4% to 13.9%, respectively), thus improving the quality of the
      biodiesel. 

PMID- 25965254
TI  - The effect of pH on solubilization of organic matter and microbial community
      structures in sludge fermentation.
AB  - Sludge fermentation between pH 4 and 11 was investigated to generate volatile
      fatty acids (VFA). Despite the highest sludge solubilization of 25.9% at pH 11,
      VFA accumulation was optimized at pH 8 (12.5% out of 13.1% sludge
      solubilization). 454 pyrosequencing identified wide diversity of acidogens in
      bioreactors operated at the various pHs, with Tissierella, Petrimonas,
      Proteiniphilum, Levilinea, Proteiniborus and Sedimentibacter enriched and
      contributing to the enhanced fermentation at pH 8. Hydrolytic enzymatic assays
      determined abiotic effect to be the leading cause for improved solubilization
      under high alkaline condition but the environmental stress at pH 9 and above
      might lead to disrupt biological activities and eventually VFA production.
      Furthermore, molecular weight (MW) characterization of the soluble fractions
      found large MW aromatic substances at pH 9 and above, that is normally associated
      with poor biodegradability, making them disadvantageous for subsequent
      bioprocesses. The findings provided information to better understand and control
      sludge fermentation. 

PMID- 25965255
TI  - Role of extracellular polymeric substances from Chlorella vulgaris in the removal
      of ammonium and orthophosphate under the stress of cadmium.
AB  - The interactions between the soluble extracellular polymeric substances (S-EPS),
      bound EPS (B-EPS) of algae and heavy metal, would affect the removal of ammonium
      (NH4(+)-N) and orthophosphate (PO4(3-)-P) from wastewater by algae-based
      techniques. This study investigated the role of Cd(2+)-mediated EPS from
      Chlorella vulgaris on NH4(+)-N and PO4(3-)-P removal. The results showed that the
      removal efficiencies of NH4(+)-N and PO4(3-)-P still separately remained 62.6%
      and 64.9% under 1.0mg/L Cd(2+), compared to those without Cd(2+), mainly
      attributing to enhanced S-EPS and B-EPS contents of the algae. The increased of
      PS (polysaccharides) and PN (proteins, e.g., tryptophan-like and tyrosine-like
      components) led to accelerated interactions of Cd(2+) with PS and PN in EPS
      fractions, especially for B-EPS, due to a higher detected distribution of Cd(2+)
      (e.g., about 55.4% in B-EPS). Thus, algae-based techniques are stable treatment
      methods for wastewater in which NH4(+)-N and PO4(3-)-P coexist with heavy metals.

PMID- 25965256
TI  - Mechanisms of ammonium assimilation by Chlorella vulgaris F1068: Isotope
      fractionation and proteomic approaches.
AB  - Removal of ammonium (NH4(+)-N) by microalgae has evoked interest in wastewater
      treatment, however, the detailed mechanisms of ammonium assimilation remain
      mysterious. This study investigated the effects of NH4(+)-N concentration on the
      removal and biotransformation efficiency by Chlorella vulgaris F1068, and
      explored the mechanisms by (15)N isotope fractionation and proteome approaches.
      The results showed NH4(+)-N was efficiently removed (84.8%) by F1068 at 10mgL(-1)
      of NH4(+)-N. The isotope enrichment factor (epsilon=-2.37+/-0.080/00) of (15)N
      isotope fractionation revealed 47.6% biotransformation at above condition, while
      7.0% biotransformation at 4mgL(-1) of NH4(+)-N (epsilon=-1.63+/-0.060/00). This
      was due to the different expression of glutamine synthetase, a key enzyme in
      ammonium assimilation, which was up-regulated 6.4-fold at proteome level and 18.0
      fold at transcription level. The results will provide a better mechanistic
      understanding of ammonium assimilation by microalgae and this green technology is
      expected to reduce the burden of NH4(+)-N removal for municipal sewage treatment
      plants. 

PMID- 25965257
TI  - Acetone-butanol-ethanol production in a novel continuous flow system.
AB  - This study investigates the potential of using a novel integrated biohydrogen
      reactor clarifier system (IBRCS) for acetone-butanol-ethanol (ABE) production
      using a mixed culture at different organic loading rates (OLRs). The results of
      this study showed that using a setting tank after the fermenter and recycle the
      settled biomass to the fermenter is a practical option to achieve high biomass
      concentration in the fermenter and thus sustainable ABE fermentation in
      continuous mode. The average ABE concentrations of 2.3, 7.0, and 14.6gABE/L which
      were corresponding to ABE production rates of 0.4, 1.4, and 2.8gABE/Lreactorh
      were achieved at OLRs of 21, 64, and 128gCOD/Lreactord, respectively. The main
      volatile fatty acids components in the effluent were acetic, propionic, and
      butyric acids. Acetic acid was the predominant component in the OLR-1, while
      butyric acid was the predominant acid in OLRs 2 and 3. 

PMID- 25965258
TI  - Environmental sustainability assessment of a microalgae raceway pond treating
      aquaculture wastewater: From up-scaling to system integration.
AB  - The environmental sustainability of aquaculture wastewater treatment by
      microalgal bacterial flocs (MaB-flocs) in an outdoor raceway pond was analyzed
      using life cycle assessment. Pikeperch aquaculture wastewater treated at pilot
      scale (Belgium; 28m(2)) and industrial scale (hypothetical up-scaling; 41 ponds
      of 245m(2)) were compared. The integration of the MaB-floc raceway pond in a
      broader aquaculture waste treatment system was studied, comparing the
      valorisation of MaB-flocs as shrimp feed and as biogas. Up-scaling improves the
      resource footprint of the plant (848MJex,CEENEkg(-1) MaB-floc TSS at pilot scale
      and 277MJex,CEENEkg(-1) MaB-floc TSS at industrial scale) as well as its carbon
      footprint and eutrophication potential. At industrial scale, the valorisation of
      MaB-flocs as shrimp feed is overall more sustainable than as biogas but
      improvements should be made to reduce the energy use of the MaB-floc raceway
      pond, especially by improving the energy-efficiency of the pond stirring system. 

PMID- 25965259
TI  - Negative Casimir entropies in nanoparticle interactions.
AB  - Negative entropy has been known in Casimir systems for some time. For example, it
      can occur between parallel metallic plates modeled by a realistic Drude
      permittivity. Less well known is that negative entropy can occur purely
      geometrically, say between a perfectly conducting sphere and a conducting plate.
      The latter effect is most pronounced in the dipole approximation, which is
      reliable when the size of the sphere is small compared to the separation between
      the sphere and the plate. Therefore, here we examine cases where negative entropy
      can occur between two electrically and magnetically polarizable nanoparticles or
      atoms, which need not be isotropic, and between such a small object and a
      conducting plate. Negative entropy can occur even between two perfectly
      conducting spheres, between two electrically polarizable nanoparticles if there
      is sufficient anisotropy, between a perfectly conducting sphere and a Drude
      sphere, and between a sufficiently anisotropic electrically polarizable
      nanoparticle and a transverse magnetic conducting plate. 

PMID- 25965261
TI  - Iterative reconstruction: Why, how and when?

PMID- 25965260
TI  - Fluorescent Silica Nanoparticles with Multivalent Inhibitory Effects towards
      Carbonic Anhydrases.
AB  - Multifunctional silica nanoparticles decorated with fluorescent and sulfonamide
      carbonic anhydrase (CA) inhibitors were prepared and investigated as multivalent
      enzyme inhibitors against the cytosolic isoforms hCA I and II and the
      transmembrane tumor-associated ones hCA IX and XII. Excellent inhibitory effects
      were observed with these nanoparticles, with KI values in the low nanomolar range
      (6.2-0.67 nM) against all tested isozymes. A significant multivalency effect was
      seen for the inhibition of the monomeric enzymes hCA I and II compared to the
      dimeric hCA IX and hCA XII isoforms, where no multivalent effect was observed,
      suggesting that the multivalent binding is occurring through enzyme clustering. 

PMID- 25965262
TI  - Hi-C Chromatin Interaction Networks Predict Co-expression in the Mouse Cortex.
AB  - The three dimensional conformation of the genome in the cell nucleus influences
      important biological processes such as gene expression regulation. Recent studies
      have shown a strong correlation between chromatin interactions and gene co
      expression. However, predicting gene co-expression from frequent long-range
      chromatin interactions remains challenging. We address this by characterizing the
      topology of the cortical chromatin interaction network using scale-aware
      topological measures. We demonstrate that based on these characterizations it is
      possible to accurately predict spatial co-expression between genes in the mouse
      cortex. Consistent with previous findings, we find that the chromatin interaction
      profile of a gene-pair is a good predictor of their spatial co-expression.
      However, the accuracy of the prediction can be substantially improved when
      chromatin interactions are described using scale-aware topological measures of
      the multi-resolution chromatin interaction network. We conclude that, for co
      expression prediction, it is necessary to take into account different levels of
      chromatin interactions ranging from direct interaction between genes (i.e. small
      scale) to chromatin compartment interactions (i.e. large-scale). 

PMID- 25965263
TI  - Edin Expression in the Fat Body Is Required in the Defense Against Parasitic
      Wasps in Drosophila melanogaster.
AB  - The cellular immune response against parasitoid wasps in Drosophila involves the
      activation, mobilization, proliferation and differentiation of different blood
      cell types. Here, we have assessed the role of Edin (elevated during infection)
      in the immune response against the parasitoid wasp Leptopilina boulardi in
      Drosophila melanogaster larvae. The expression of edin was induced within hours
      after a wasp infection in larval fat bodies. Using tissue-specific RNAi, we show
      that Edin is an important determinant of the encapsulation response. Although
      edin expression in the fat body was required for the larvae to mount a normal
      encapsulation response, it was dispensable in hemocytes. Edin expression in the
      fat body was not required for lamellocyte differentiation, but it was needed for
      the increase in plasmatocyte numbers and for the release of sessile hemocytes
      into the hemolymph. We conclude that edin expression in the fat body affects the
      outcome of a wasp infection by regulating the increase of plasmatocyte numbers
      and the mobilization of sessile hemocytes in Drosophila larvae. 

PMID- 25965264
TI  - Differentiating Biological Colours with Few and Many Sensors: Spectral
      Reconstruction with RGB and Hyperspectral Cameras.
AB  - BACKGROUND: The ability to discriminate between two similar or progressively
      dissimilar colours is important for many animals as it allows for accurately
      interpreting visual signals produced by key target stimuli or distractor
      information. Spectrophotometry objectively measures the spectral characteristics
      of these signals, but is often limited to point samples that could underestimate
      spectral variability within a single sample. Algorithms for RGB images and
      digital imaging devices with many more than three channels, hyperspectral
      cameras, have been recently developed to produce image spectrophotometers to
      recover reflectance spectra at individual pixel locations. We compare a
      linearised RGB and a hyperspectral camera in terms of their individual capacities
      to discriminate between colour targets of varying perceptual similarity for a
      human observer. MAIN FINDINGS: (1) The colour discrimination power of the RGB
      device is dependent on colour similarity between the samples whilst the
      hyperspectral device enables the reconstruction of a unique spectrum for each
      sampled pixel location independently from their chromatic appearance. (2)
      Uncertainty associated with spectral reconstruction from RGB responses results
      from the joint effect of metamerism and spectral variability within a single
      sample. CONCLUSION: (1) RGB devices give a valuable insight into the limitations
      of colour discrimination with a low number of photoreceptors, as the principles
      involved in the interpretation of photoreceptor signals in trichromatic animals
      also apply to RGB camera responses. (2) The hyperspectral camera architecture
      provides means to explore other important aspects of colour vision like the
      perception of certain types of camouflage and colour constancy where multiple,
      narrow-band sensors increase resolution.

PMID- 25965265
TI  - Hepatitis C Virus NS3 Mediated Microglial Inflammation via TLR2/TLR6 MyD88/NF
      kappaB Pathway and Toll Like Receptor Ligand Treatment Furnished Immune
      Tolerance.
AB  - BACKGROUND: Recent evidence suggests the neurotrophic potential of hepatitis C
      virus (HCV). HCV NS3 protein is one of the potent antigens of this virus
      mediating inflammatory response in different cell types. Microglia being the
      immune surveillance cells in the central nervous system (CNS), the inflammatory
      potential of NS3 on microglia was studied. Role of toll like receptor (TLR)
      ligands Pam2CSK3 and Pam3CSK4 in controlling the NS3 mediated microglial
      inflammation was studied using microglial cell line CHME3. METHODS: IL
      (Interleukin)-8, IL-6, TNF-alpha (Tumor nicrosis factor alpha) and IL-1beta gene
      expressions were measured by semi quantitative RT-PCR (reverse transcription
      PCR). ELISA was performed to detect IL-8, IL-6, TNF-alpha, IL-1beta and IL-10
      secretion. FACS (Flourescent activated cell sorting) was performed to quantify
      TLR1, TLR2, TLR6, MyD88 (Myeloid differntiation factor 88), IkB-alpha (I kappaB
      alpha) and pNF-kappaB (phosphorylated nuclear factor kappaB) expression.
      Immunofluorescence staining was performed for MyD88, TLR6 and NF-kappaB (Nuclear
      factor kappaB). Student's t-test or One way analysis of variance with Bonferoni
      post hoc test was performed and p < 0.05 was considered significant. RESULTS:
      Microglia responded to NS3 by secreting IL-8, IL-6, TNF-alpha and IL-1beta via
      TLR2 or TLR6 mediated MyD88/NF-kappaB pathway. Transcription factor NF-kappaB was
      involved in activating the cytokine gene expression and the resultant
      inflammatory response was controlled by NF-kappaB inhibitor, Ro106-9920, which is
      known to down regulate pro-inflammatory cytokine secretion. Activation of the
      microglia by TLR agonists Pam3CSK4 and Pam2CSK4 induced immune tolerance against
      NS3. TLR ligand treatment significantly down regulated pro-inflammatory cytokine
      secretion in the microglia. IL-10 secretion was suggested as the possible
      mechanism by which TLR agonists induced immune tolerance. NS3 as such was not
      capable of self-inducing immune tolerance in microglia. CONCLUSION: In
      conclusion, NS3 protein was capable of activating microglia and the inflammatory
      response could be controlled via blocking the transcription factor NF-kappaB, or
      by treating the microglia with TLR ligands which likely function via secreting
      anti-inflammatory cytokines such as IL-10. This can have therapeutic potential in
      controlling HCV mediated neuroinflammation.

PMID- 25965266
TI  - Optimization of translation profiles enhances protein expression and solubility.
AB  - mRNA is translated with a non-uniform speed that actively coordinates co
      translational folding of protein domains. Using structure-based homology we
      identified the structural domains in epoxide hydrolases (EHs) and introduced slow
      translating codons to delineate the translation of single domains. These changes
      in translation speed dramatically improved the solubility of two EHs of
      metagenomic origin in Escherichia coli. Conversely, the importance of transient
      attenuation for the folding, and consequently solubility, of EH was evidenced
      with a member of the EH family from Agrobacterium radiobacter, which partitions
      in the soluble fraction when expressed in E. coli. Synonymous substitutions of
      codons shaping the slow-transiting regions to fast-translating codons render this
      protein insoluble. Furthermore, we show that low protein yield can be enhanced by
      decreasing the free folding energy of the initial 5'-coding region, which can
      disrupt mRNA secondary structure and enhance ribosomal loading. This study
      provides direct experimental evidence that mRNA is not a mere messenger for
      translation of codons into amino acids but bears an additional layer of
      information for folding, solubility and expression level of the encoded protein.
      Furthermore, it provides a general frame on how to modulate and fine-tune gene
      expression of a target protein. 

PMID- 25965268
TI  - Vibrotactile timing: Are vibrotactile judgements of duration affected by
      repetitive stimulation?
AB  - Timing in the vibrotactile modality was explored. Previous research has shown
      that repetitive auditory stimulation (in the form of click-trains) and visual
      stimulation (in the form of flickers) can alter duration judgements in a manner
      consistent with a "speeding up" of an internal clock. In Experiments 1 and 2 we
      investigated whether repetitive vibrotactile stimulation in the form of vibration
      trains would also alter duration judgements of either vibrotactile stimuli or
      visual stimuli. Participants gave verbal estimates of the duration of
      vibrotactile and visual stimuli that were preceded either by five seconds of 5-Hz
      vibration trains, or, by a five-second period of no vibrotactile stimulation, the
      end of which was signalled by a single vibration pulse (control condition). The
      results showed that durations were overestimated in the vibrotactile train
      conditions relative to the control condition; however, the effects were not
      multiplicative (did not increase with increasing stimulus duration) and as such
      were not consistent with a speeding up of the internal clock, but rather with an
      additive attentional effect. An additional finding was that the slope of the
      vibrotactile psychometric (control condition) function was not significantly
      different from that of the visual (control condition) function, which replicates
      a finding from a previous cross-modal comparison of timing. 

PMID- 25965267
TI  - Developmental Competence of Vitrified-Warmed Bovine Oocytes at the Germinal
      Vesicle Stage is Improved by Cyclic Adenosine Monophosphate Modulators during In
      Vitro Maturation.
AB  - Cryopreservation of mature oocytes and embryos has provided numerous benefits in
      reproductive medicine. Although successful cryopreservation of germinal-vesicle
      stage (GV) oocytes holds promise for further advances in reproductive biology and
      clinical embryology fields, reports regarding cryopreservation of immature
      oocytes are limited. Oocyte survival and maturation rates have improved since
      vitrification is being performed at the GV stage, but the subsequent
      developmental competence of GV oocytes is still low. The purpose of this study
      was to evaluate the effects of supplementation of the maturation medium with
      cyclic adenosine monophosphate (cAMP) modulators on the developmental competence
      of vitrified-warmed GV bovine oocytes. GV oocytes were vitrified-warmed and
      cultured to allow for oocyte maturation, and then parthenogenetically activated
      or fertilized in vitro. Our results indicate that addition of a cAMP modulator
      forskolin (FSK) or 3-isobutyl-1-methylxanthine (IBMX) to the maturation medium
      significantly improved the developmental competence of vitrified-warmed GV
      oocytes. We also demonstrated that vitrification of GV oocytes led to a decline
      in cAMP levels and maturation-promoting factor (MPF) activity in the oocytes
      during the initial and final phases of maturation, respectively. Nevertheless,
      the addition of FSK or IBMX to the maturation medium significantly elevated cAMP
      levels and MPF activity during IVM. Taken together, our results suggest that the
      cryopreservation-associated meiotic and developmental abnormalities observed in
      GV oocytes may be ameliorated by an artificial increase in cAMP levels during
      maturation culture after warming. 

PMID- 25965269
TI  - Inflammatory Signalling in Fetal Membranes: Increased Expression Levels of TLR 1
      in the Presence of Preterm Histological Chorioamnionitis.
AB  - Histological chorioamnionitis (HCA) is an established marker of ascending
      infection, a major cause of preterm birth. No studies have characterised the
      global change in expression of genes involved in the toll-like receptor (TLR)
      signalling pathways in the presence of HCA in the setting of preterm birth
      (pHCA). Fetal membranes were collected immediately after delivery and underwent
      histological staging for inflammation to derive 3 groups; term spontaneous labour
      without HCA (n = 9), preterm birth <34 weeks gestation without HCA (n = 8) and
      pHCA <34 weeks (n = 12). Profiling arrays ran in triplicate for each group were
      used to determine the expression of 84 genes associated with TLR signalling and
      screen for genes of interest (fold change >2; p<0.1). Expression of identified
      genes was validated individually for all samples, relative to GAPDH, using RT
      PCR. Expression of TLR 1, TLR 2, lymphocyte antigen 96, interleukin 8 and
      Interleukin-1 receptor-associated kinase-like 2 was increased in pHCA (p<0.05).
      Degree of expression was positively associated with histological staging of both
      maternal and fetal inflammation (p<0.05). The inflammatory expression profile at
      the maternal/fetal interface associated with pHCA, a reflection of ascending
      infection, is extremely heterogeneous suggesting polymicrobial involvement with
      activation of a common pathway. Antagonism of TLR 1 and TLR 2 signalling in this
      setting warrants further assessment. 

PMID- 25965270
TI  - Clinical Outcome among Nasopharyngeal Cancer Patients in a Multi-Ethnic Society
      in Singapore.
AB  - BACKGROUND: Nasopharyngeal cancer (NPC) is endemic among Chinese populations in
      Southeast Asia. However, the outcomes of non-Chinese NPC patients in Singapore
      are not well reported. AIM: To determine if non-Chinese NPC patients have a
      different prognosis and examine the clinical outcomes of NPC patients in a multi
      ethnic society. METHODS: Retrospective chart review of 558 NPC patients treated
      at a single academic tertiary hospital from 2002 to 2012. Survival and recurrence
      rates were analysed and predictive factors identified using the Kaplan-Meier
      method and Cox regression model. RESULTS: Our cohort comprised 409 males (73.3%)
      and 149 females (26.7%) with a median age of 52 years. There were 476 Chinese
      (85.3%), 57 Malays (10.2%), and 25 of other ethnic groups (4.5%). Non-Chinese
      patients were more likely to be associated with advanced nodal disease at initial
      presentation (p = 0.049), compared with the Chinese. However, there were no
      statistical differences in their overall survival (OS) or disease specific
      survival (DSS) (p = 0.934 and p = 0.857 respectively). The 3-year and 5-year
      cohort OS and DSS rates were 79.3%, 70.7%, and 83.2%, 77.4% respectively.
      Advanced age (p<0.001), N2 disease (p = 0.036), N3 disease (p<0.001), and
      metastatic disease (p<0.001) at presentation were independently associated with
      poor overall survival. N2 disease (p = 0.032), N3 disease (p<0.001) and
      metastatic disease (p<0.001) were also independently associated with poor DSS. No
      predictive factors were associated with loco-regional recurrence after definitive
      treatment. Advanced age (p = 0.044), N2 disease (p = 0.033) and N3 disease
      (p<0.001) were independently associated with distant relapse. CONCLUSION: In a
      multi-ethnic society in Singapore, non-Chinese are more likely to present with
      advanced nodal disease. This however did not translate into poorer survival
      outcomes. Older patients with N2 or N3 disease are associated with a higher risk
      of distant relapse and poor overall survival.

PMID- 25965271
TI  - Predictive models to determine imagery strategies employed by children to judge
      hand laterality.
AB  - A commonly used paradigm to study motor imagery is the hand laterality judgment
      task. The present study aimed to determine which strategies young children employ
      to successfully perform this task. Children of 5 to 8 years old (N = 92) judged
      laterality of back and palm view hand pictures in different rotation angles.
      Response accuracy and response duration were registered. Response durations of
      the trials with a correct judgment were fitted to a-priori defined predictive
      sinusoid models, representing different strategies to successfully perform the
      hand laterality judgment task. The first model predicted systematic changes in
      response duration as a function of rotation angle of the displayed hand. The
      second model predicted that response durations are affected by biomechanical
      constraints of hand rotation. If observed data could be best described by the
      first model, this would argue for a mental imagery strategy that does not involve
      motor processes to solve the task. The second model reflects a motor imagery
      strategy to solve the task. In line with previous research, we showed an age
      related increase in response accuracy and decrease in response duration in
      children. Observed data for both back and palm view showed that motor imagery
      strategies were used to perform hand laterality judgments, but that not all the
      children use these strategies (appropriately) at all times. A direct comparison
      of response duration patterns across age sheds new light on age-related
      differences in the strategies employed to solve the task. Importantly, the
      employment of the motor imagery strategy for successful task performance did not
      change with age. 

PMID- 25965272
TI  - Transcriptome Analysis Comparison of Lipid Biosynthesis in the Leaves and
      Developing Seeds of Brassica napus.
AB  - Brassica napus seed is a lipid storage organ containing approximately 40% oil,
      while its leaves contain many kinds of lipids for many biological roles, but the
      overall amounts are less than in seeds. Thus, lipid biosynthesis in the
      developing seeds and the leaves is strictly regulated which results the final
      difference of lipids. However, there are few reports about the molecular
      mechanism controlling the difference in lipid biosynthesis between developing
      seeds and leaves. In this study, we tried to uncover this mechanism by analyzing
      the transcriptome data for lipid biosynthesis. The transcriptome data were de
      novo assembled and a total of 47,216 unigenes were obtained, which had an N50
      length and median of 1271 and 755 bp, respectively. Among these unigenes, 36,368
      (about 77.02%) were annotated and there were 109 up-regulated unigenes and 72
      down-regulated unigenes in the developing seeds lipid synthetic pathway after
      comparing with leaves. In the oleic acid pathway, 23 unigenes were up-regulated
      and four unigenes were down-regulated. During triacylglycerol (TAG) synthesis,
      the key unigenes were all up-regulated, such as phosphatidate phosphatase and
      diacylglycerol O-acyltransferase. During palmitic acid, palmitoleic acid, stearic
      acid, linoleic acid and linolenic acid synthesis in leaves, the unigenes were
      nearly all up-regulated, which indicated that the biosynthesis of these
      particular fatty acids were more important in leaves. In the developing seeds,
      almost all the unigenes in the ABI3VP1, RKD, CPP, E2F-DP, GRF, JUMONJI, MYB
      related, PHD and REM transcript factor families were up-regulated, which helped
      us to discern the regulation mechanism underlying lipid biosynthesis. The
      differential up/down-regulation of the genes and TFs involved in lipid
      biosynthesis in developing seeds and leaves provided direct evidence that allowed
      us to map the network that regulates lipid biosynthesis, and the identification
      of new TFs that are up-regulated in developing seeds will help us to further
      elucidate the lipids biosynthesis pathway in developing seeds and leaves.

PMID- 25965273
TI  - Adverse childhood experiences influence development of pain during pregnancy.
AB  - OBJECTIVE: To investigate the association between adverse childhood experiences
      (ACE) and pain with onset during pregnancy. DESIGN: Cross-sectional study.
      SETTING: Eighteen antenatal clinics in southern Mid-Sweden. SAMPLE: Of 293 women
      invited to participate, 232 (79%) women agreed to participate in early pregnancy
      and were assessed in late pregnancy. METHODS: Questionnaires were distributed in
      early and late pregnancy. The questionnaires sought information on socio
      demography, ACE, pain location by pain drawing and pain intensity by visual
      analogue scales. Distribution of pain was coded in 41 predetermined areas. MAIN
      OUTCOME MEASURES: Pain in third trimester with onset during present pregnancy:
      intensity, location and number of pain locations. RESULTS: In late pregnancy, 62%
      of the women reported any ACE and 72% reported any pain location with onset
      during the present pregnancy. Among women reporting any ACE the median pain
      intensity was higher compared with women without such an experience (p = 0.01).
      The accumulated ACE displayed a positive association with the number of reported
      pain locations in late pregnancy (rs = 0.19, p = 0.02). This association remained
      significant after adjusting for background factors in multiple regression
      analysis (p = 0.01). When ACE was dichotomized the prevalence of pain did not
      differ between women with and without ACE. The subgroup of women reporting
      physical abuse as a child reported a higher prevalence of sacral and pelvic pain
      (p = 0.0003 and p = 0.02, respectively). CONCLUSIONS: Adverse childhood
      experiences were associated with higher pain intensities and larger pain
      distributions in late pregnancy, which are risk factors for transition to chronic
      pain postpartum.

PMID- 25965274
TI  - Characterization of Protein Structural Changes in Living Cells Using Time-Lapsed
      FTIR Imaging.
AB  - Fourier-transform infrared (FTIR) spectroscopic imaging is a widely used method
      for studying the chemistry of proteins, lipids, and DNA in biological systems
      without the need for additional tagging or labeling. This technique can be
      especially powerful for spatially resolved, temporal studies of dynamic changes
      such as in vivo protein folding in cell culture models. However, FTIR imaging
      experiments have typically been limited to dry samples as a result of the
      significant spectral overlap between water and the protein Amide I band centered
      at 1650 cm(-1). Here, we demonstrate a method to rapidly obtain high quality FTIR
      spectral images at submicron pixel resolution in vivo over a duration of 18 h and
      longer through the development and use of a custom-built, demountable,
      microfluidic-incubator and a FTIR microscope coupled to a focal plane array (FPA)
      detector and a synchrotron light source. The combined system maximizes ease of
      use by allowing a user to perform standard cell culture techniques and
      experimental manipulation outside of the microfluidic-incubator, where assembly
      can be done just before the start of experimentation. The microfluidic-incubator
      provides an optimal path length of 6-8 MUm and a submillimeter working distance
      in order to obtain FTIR images with 0.54-0.77 MUm pixel resolution. In addition,
      we demonstrate a novel method for the correction of spectral distortions caused
      by varying concentrations of water over a subconfluent field of cells. Lastly, we
      use the microfluidic-incubator and time-lapsed FTIR imaging to determine the
      misfolding pathway of mutant copper-zinc superoxide dismutase (SOD1), the protein
      known to be a cause of familial amyotrophic lateral sclerosis (FALS). 

PMID- 25965275
TI  - Significance of the Immunohistochemical Expression of Bone Morphogenetic Protein
      4 in Bone Maturation after Maxillary Sinus Grafting in Humans.
AB  - BACKGROUND: Bone morphogenetic proteins (BMPs) are members of the transforming
      growth factor-beta (TGFbeta) protein superfamily and are known to be involved in
      bone and cartilage formation. Within this family, BMP-4 is one of the most
      studied members. It has been shown to induce osteogenic differentiation of
      osteoblasts and osteoprogenitor cells in vitro, but the intimate processes in
      which this protein promotes and regulates osseous repair still remains unclear.
      PURPOSE: To assess whether the native cellular immunohistochemical expression of
      BMP-4 correlates with the maturation of bone samples obtained at 6 months after
      maxillary sinus augmentation. MATERIALS AND METHODS: Histopathological and
      histomorphometrical analyses were performed in all the samples, which were
      obtained from a total of 58 patients. Immunohistochemical expression of BMP-4 was
      analyzed in 30 core biopsies obtained from maxillary sinuses grafted with a
      combination of anorganic bovine bone and autogenous cortical bone [1:1] (AB
      group), and 18 biopsies from maxillary sinuses grafted solely with a cortico
      cancellous particulate allograft (M-group), all of them after a 6-month healing
      period. Also, 10 biopsies of native pristine bone were obtained and used as
      control group (C-group). RESULTS: Mild to moderate immunohistochemical expression
      of native granular BMP-4 was present in 56.8% (31.0% AB-group, 22.4% M-group, and
      3.4% C-group) (p = 0.000, chi-square) of the specimens analyzed. BMP-4 expression
      was primarily located in the cytoplasm of osteoblasts, osteoclasts, and
      epithelial cells of the schneiderian membrane. Whereas significant differences
      were observed in the proportion of mineralized tissue and cellularity between
      sinuses grafted with anorganic bovine bone, allograft, or nongrafted sinuses,
      there were no statistically significant differences in the cellular expression of
      BMP-4 among groups. CONCLUSION: Our findings suggest that the native expression
      of BMP-4 appears to be associated with normal bone homeostasis and reparation in
      grafted and nongrafted maxillary sites.

PMID- 25965276
TI  - Does forming implementation intentions help people with mental health problems to
      achieve goals? A meta-analysis of experimental studies with clinical and analogue
      samples.
AB  - OBJECTIVE: People struggle to act on the goals that they set themselves, and this
      gap between intention and action is likely to be exacerbated by mental health
      problems. Evidence suggests that forming specific if-then plans (or
      'implementation intentions') can promote goal attainment and a number of studies
      have applied such techniques in clinical contexts. However, to date, the extent
      to which planning can help people with mental health problems has not been
      systematically examined. METHOD: The present review used meta-analysis to
      investigate the effect of if-then planning on goal attainment among people with a
      DSM-IV/ICD-10 diagnosis (i.e., clinical samples) or scores above a relevant cut
      off on clinical measures (i.e., analogue samples). In total, 29 experimental
      studies, from 18 records, met the inclusion criteria. RESULTS: Excluding one
      outlying (very large) effect, forming implementation intentions had a large-sized
      effect on goal attainment (d+ = 0.99, k = 28, N = 1,636). Implementation
      intentions proved effective across different mental health problems and goals,
      and in studies with different methodological approaches. CONCLUSIONS: Taken
      together, the findings suggest that forming implementation intentions can be a
      useful strategy for helping people with mental health problems to achieve various
      goals and might be usefully integrated into existing treatment approaches.
      However, further studies are needed addressing a wider range of mental health
      problems.

PMID- 25965277
TI  - The role of phonological awareness and letter-sound knowledge in the reading
      development of children with intellectual disabilities.
AB  - Our study investigated if phonological awareness and letter-sound knowledge were
      predictors of reading progress in children with intellectual disabilities (ID)
      with unspecified etiology. An academic achievement test was administered to 129
      children with mild or moderate ID when they were 6-8 years old, as well as one
      and two school years later. Findings indicated that phonological awareness and
      letter-sound knowledge at 6-8 years of age predicted progress in word and non
      word reading after one school year and two school years after controlling for IQ,
      age, expressive vocabulary, spoken language, and type of placement. Phonological
      awareness and letter-sound knowledge at 6-8 years of age also predicted progress
      in reading comprehension after one school year and two school years. These
      findings suggest that training phonological awareness skills combined with
      explicit phonics instruction is important to foster reading progress in children
      with mild and moderate ID with unspecified etiology. 

PMID- 25965278
TI  - Gradient-echo 3D imaging of Rb polarization in fiber-coupled atomic magnetometer.
AB  - The analogy between atomic and nuclear spins is exploited to implement 3D imaging
      of polarization inside the cell of an atomic magnetometer. The resolution of
      0.8mm*1.2mm*1.4mm has been demonstrated with the gradient-echo imaging method.
      The imaging can be used in many applications. One such an application is the
      evaluation of active volume of an atomic magnetometer for sensitivity analysis
      and optimization. It has been found that imaging resolution is limited due to de
      phasing from spin-exchange collisions and diffusion in the presence of gradients,
      and for a given magnetometer operational parameters, the imaging sequence has
      been optimized. Diffusion decay of the signal in the presence of gradients has
      been modeled numerically and analytically, and the analytical results, which
      agreed with numerical simulations, have been used to fit the spin-echo gradient
      measurements to extract the diffusion coefficient. The diffusion coefficient was
      found in agreement with previous measurements. 

PMID- 25965279
TI  - Optimization of cross-polarization at low radiofrequency fields for sensitivity
      enhancement in solid-state NMR of membrane proteins reconstituted in magnetically
      aligned bicelles.
AB  - Solid-state NMR (ssNMR) of oriented membrane proteins (MPs) is capable of
      providing structural and dynamic information at nearly physiological conditions.
      However, NMR experiments performed on oriented membrane proteins generally suffer
      from low sensitivity. Moreover, utilization of high-power radiofrequency (RF)
      irradiations for magnetization transfer may give rise to sample heating, thereby
      decreasing the efficiency of conventional cross-polarization schemes. Here we
      have optimized the recently developed repetitive cross-polarization (REP-CP)
      sequence (Tang et al., 2011) to further increase the magnetization transfer
      efficiency for membrane proteins reconstituted in magnetically aligned bicelles
      and compared its performance to single-contact Hartmann-Hahn cross-polarization
      (CP), CP-MOIST and the adiabatic transfer. It has been found that employing the
      REP-CP sequence at RF amplitudes of 19kHz instead of the commonly used higher RF
      fields (>45kHz) enhances the efficiency of REP-CP. An additional 30% signal can
      be obtained as compared to the previously published REP-CP, and 20% when compared
      to the re-optimized REP-CP at 50kHz RF fields. Moreover, the (15)N signal gain of
      low-power REP-CP was found to be 40% over the adiabatic CP and up to 80% over CP
      MOIST. Thus, the low-power REP-CP sequence surpasses all of the previous CP
      schemes in addition of having the tremendous advantage of reducing the RF powers
      by a factor of seven, thereby preserving the liquid-like bicelle sample. By
      contrast, in purely static (NAL crystal) and semi-rigid systems (Pf1 phage), the
      adiabatic CP was found to be more effective. Periodic oscillations of the
      intensity profile (distinct from the transient oscillations) as a function of the
      CP contact time and B1 RF field strengths were observed during the REP-CP
      optimization with the oscillations becoming more pronounced with lower RF fields.
      Many-spin simulations were performed to explain the oscillations and their
      periodicity. 

PMID- 25965280
TI  - Spin-locking and cross-polarization under magic-angle spinning of uniformly
      labeled solids.
AB  - Spin-locking and cross-polarization under magic-angle spinning are investigated
      for uniformly (13)C and (15)N labeled solids. In particular, the interferences
      from chemical shift anisotropy, and (1)H heteronuclear and (13)C homonuclear
      dipolar couplings are identified. The physical origin of these interferences
      provides guidelines for selecting the best (13)C and (15)N polarization transfer
      rf fields. Optimal settings for both the zero- and double-quantum cross
      polarization transfer mechanisms are recommended. 

PMID- 25965281
TI  - An off-the-shelf plasma-based material to prevent pacemaker pocket infection.
AB  - Bacterial infection of subcutaneous "pockets" housing cardiovascular implantable
      electronic devices is a significant clinical complication. In this study,
      pacemakers encapsulated in a blood plasma-based material (PBM) composited with
      antibiotics were investigated for use as prophylactics against such infections.
      PBMs, which are made from pooled allogeneic plasma and platelets, are off-the
      shelf biomaterials that can be manufactured in the form of complex 3D shapes,
      extrudable putties, or injectable pastes. In vitro studies with PBM pastes
      formulated with rifampicin and minocycline demonstrated antibiotic release over 6
      days, activity against Escherichia coli, and reduced cytotoxic effects of the
      antibiotics on fibroblasts. The materials were also evaluated in vivo in a rabbit
      model in which pacemaker pockets were inoculated with methicillin-resistant
      Staphylococcus aureus (S. aureus) strain and examined 1 week later. The pockets
      containing the pacemaker plus S. aureus were grossly purulent and culture
      positive, whereas pockets into which PBM with antibiotics were injected around
      the pacemaker were free of purulence and culture negative (p < 0.001). None of
      the pockets into which PBM without antibiotics were placed demonstrated
      purulence, but 60% were culture positive. These results demonstrate the potential
      of PBMs to deliver antibiotics to diminish the incidence of pocket infections for
      pacemakers and other implantable devices. 

PMID- 25965282
TI  - The effect of blocking angiogenesis on anterior cruciate ligament healing
      following stem cell transplantation.
AB  - Ruptured human anterior cruciate ligaments (ACL) contain vascular stem cells
      capable of enhancing the healing of tendon grafts. In the current study we
      explored the role that neo-angiogenesis plays in ACL healing. ACL-derived CD34+
      cells were isolated via Fluorescence Activated Cell Sorting (FACS) from the
      rupture sites of human ACLs. The cells were then virally transduced to express
      either vascular endothelial growth factor (VEGF) or soluble FLT-1 (sFLT-1), which
      is an antagonist of VEGF. We established five groups: CD34+VEGF(100%), where 100%
      of the cells were transduced with VEGF, CD34+VEGF(25%), where only 25% of the
      cells were transduced with VEGF, CD34+, CD34+sFLT-1, and a No cells group. The
      CD34+sFLT1 group had a significant reduction in biomechanical strength compared
      to the CD34+ group at 4 and 8 weeks; whereas the biomechanical strength of the
      CD34+VEGF(25%) group was significantly greater than the CD34+ group at week 4;
      however, no difference was observed by week 8. Immunohistochemical staining
      demonstrated a significantly lower number of isolectin B4 and hCD31 positive
      cells, markers associated with angiogenesis, in the CD34+sFLT1 group, and a
      higher number of isolectin B4 and hCD31 positive cells in the CD34+VEGF(100%) and
      CD34+VEGF(25%) groups compared to the CD34+ group. Graft maturation was
      significantly delayed in the CD34+sFLT1 group and accelerated in the
      CD34+VEGF(25%) group compared to the CD34+ group. In conclusion, blocking VEGF
      reduced angiogenesis, graft maturation and biomechanical strength following ACL
      reconstruction. Native expression of VEGF by the CD34+ cells improved tendon
      graft maturation and biomechanical strength; however, over-expression of VEGF
      impeded improvements in biomechanical strength. 

PMID- 25965285
TI  - Role of maximal inspiratory presure in the evaluetion of respiratory muscle
      strength in asthmatics - Systematic review.
AB  - Asthma is a chronic illness of the airways that can reduce respiratory muscle
      strength due to the resulting hyperinflation or treatment with corticosteroids.
      One of the ways to evaluate this respiratory muscular weakness is the Maximal
      Inspiratory Pressure (PImax). METHODS: A systematic review of the databases
      PUBMED/MEDLINE, LILACS and SCIELO was carried through, using the key words:
      Asthma, respiratory muscle and muscle strength. RESULTS: Fifty were found and six
      articles that evaluated the PImax in asthmatics, from these, thirty were
      excluded, making a total of twenty six articles. FINAL CONSIDERATIONS: Through
      the present revision we show the effectiveness of PImax in evaluating respiratory
      muscle strength in asthmatics. More studies are needed, however, fot better
      understanding of the asthmatic individual. Rev Port Pneumol 2010; XVI (3): 463
      470.

PMID- 25965286
TI  - Felix Platter and a historical perspective of the meningioma.
AB  - INTRODUCTION: Felix Platter is one of the pioneer anatomists and physicians of
      the 16th century who described various human diseases including meningioma. In
      this historical article, we present the details of Platter's life and his
      pioneering work on meningioma. FIRST CASE OF MENINGIOMA: In 1614, Dr. Platter
      described the first case of meningioma. He described the tumor as a round, fleshy
      mass shaped like an acorn and as large as a medium-sized apple, and full of
      holes. The tumor was covered with its own membrane, had no connection with the
      matters of the brain, and left behind a cavity after removal. This first clear
      description of an intracranial tumor is most consistent with encapsulated
      meningioma. The succeeding scholar, Harvey Cushing, coined the term "meningioma"
      for this tumor; neurosurgeons today describe the tumor as "parasagittal or
      falcine meningioma." OTHER CONTRIBUTIONS: In addition to his contribution to
      meningioma study, Dr. Platter was also the first to describe Dupuytren's disease,
      hypertrophy of the thalamus, and the retina as the sensory organ of the eye. He
      contributed to the germ theory of disease and gave substantial accounts of mental
      illnesses, gynecological disorders, and certain dermatological conditions.
      PUBLICATIONS: Dr. Platter published numerous accounts on various diseases. In
      1614 he reported the case of meningioma in the book entitled "Platerus
      Observations in Hominis". Additionally, Dr. Platter published his work, 'Praxeos
      Medicae,' which contains his most important contribution on psychiatry and his
      classification of psychiatric diseases. CONCLUSION: Because of his many
      contributions to neuroscience, particularly his identification of meningioma, Dr.
      Platter should be highly credited as a pioneer in the field of neurosurgery.

PMID- 25965287
TI  - Neuromyelitis optica in Portugal (NEMIPORT) - A multicentre study.
AB  - BACKGROUND: Neuromyelitis Optica (NMO) is an inflammatory demyelinating disease
      of the CNS. There have been few epidemiologic studies on NMO, none in Portugal.
      OBJECTIVE: To analyze the clinical, biological and MRI characteristics from a
      cohort of Portuguese patients who fulfilled the Wingerchuk 2006 NMO/NMOSD
      criteria. To identify and characterize those who had concomitant autoimmune
      disease or circulating autoantibodies. METHODS: We performed an observational,
      retrospective, multicenter study in 5 Hospital Centers in Portugal. RESULTS:
      Sixty-seven patients fulfilled the inclusion criteria. They were mainly
      Caucasian, 55 female. Median age at onset was 32.0 years and mean follow-up 7.4+/
      6.0 years. Twenty-one patients were definite NMO and optic neuritis (ON) the most
      frequent initial presentation. Forty-six were classified as NMO spectrum
      disorders. The main subtypes were recurrent ON and single longitudinally
      extensive transverse myelitis. Twenty-four patients had positive AQP4-IgG. Twenty
      three had other circulating autoantibodies. Fifteen out of 67 patients had
      concomitant autoimmune disease. There was a significant correlation between the
      presence of autoimmune disease and the positivity for AQP4-IgG. Five patients
      died, all definite NMO. CONCLUSION: This is the first study about this rare
      disease in Portugal. Demographic features were similar to other studies. The
      existence of concomitant autoimmune disease was significantly associated with
      seropositivity for AQP4-IgG.

PMID- 25965288
TI  - Long-term distribution of biodegradable microparticles in rat muscle quantified
      noninvasively by MRI.
AB  - PURPOSE: To demonstrate the feasibility of MRI to monitor longitudinally the fate
      of PLGA microparticles in muscle tissue after intramuscular injection in rats
      using standard equipment. METHODS: MRI was performed at different time points and
      until day 28 after intramuscular administration of microparticles. Image
      segmentation was used to quantify the MRI signals. Histology was performed at
      selected time points to validate the in vivo observations. The SOM230-long acting
      release formulation was used as test compound. RESULTS: Microparticles were
      detected in vivo until 28 days following their administration. Imaging and
      histology data indicated that the MRI signals followed three phases: in an early
      phase (<= 48 h after injection), vehicle, edema and hydration of microparticles
      contributed to the signals. In the second (days 3-17) and third phases (day 17
      onward), microparticle hydration was the main contributor. SOM230 in blood
      displayed peaks at days 2 and 17. CONCLUSION: MRI was suitable to follow
      longitudinally the presence of PLGA microparticles in the rat muscle without
      labeling them. This is advantageous, because labeling could potentially alter the
      properties and pharmacokinetics of the microparticles. Data were consistent with
      an initial compound release followed by diffusion and microparticle erosion as
      main mechanisms of SOM230 release.

PMID- 25965289
TI  - Current exposure of Italian women of reproductive age to PFOS and PFOA: A human
      biomonitoring study.
AB  - Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) concentrations
      were determined in serum samples collected in 2011-2012 from 549 nulliparous
      Italian women of reproductive age who resided in six different Italian Regions.
      Assessment of exposure to perfluorinated compounds was part of a large human
      biomonitoring study (Project Life Plus "Womenbiopop") that aimed at examining the
      exposure of women of reproductive age to priority organic pollutants. The median
      concentrations of PFOS and PFOA were 2.43, and 1.55 ng g(-1), respectively.
      Significant differences in the concentrations of both compounds were observed
      among the six Regions. Women from central Italy had the highest levels of both
      compounds, followed by women from northern Italy, and southern Italy. No
      differences in the PFOS concentrations were found between women from
      urban/industrial areas and women from rural areas, whereas the levels of PFOA
      were significantly higher in women residing in urban/industrial areas than in
      women residing in rural areas. Taken together, the observed concentrations
      confirm that the overall exposure of the Italian population is among the lowest
      observed in industrialized countries. A downward temporal trend in exposure was
      observed for both compounds when comparing the results from the present study
      with those assessed in a study conducted in 2008.

PMID- 25965290
TI  - Characterizing the distribution of selected PBDEs in soil, moss and reindeer dung
      at Ny-Alesund of the Arctic.
AB  - Distribution of 12 selected polybrominated diphenyl ethers (PBDEs) was
      characterized in soil, moss and reindeer dung samples collected simultaneously at
      Ny-Alesund of the Arctic. The average PBDE concentrations were 42 pg/g (dry
      weight) in soil, 122 pg/g in moss and 72 pg/g in reindeer dung. Significant
      log/log-linear relationship was observed between the soil/moss quotients (QSM)
      and the sub-cooled liquid vapor pressures of PBDEs (r(2)=0.80). Moreover,
      excellent log/log-linear relationships between QSM and the octanol/air partition
      coefficients as well as between the moss/dung quotient (QMD) and the
      octanol/water partition coefficients of PBDEs were also observed, indicating that
      the physicochemical properties of PBDEs are appropriate parameters for
      characterizing the distribution of PBDEs in soil, moss and reindeer dung at Ny
      Alesund. Capsule abstract: Significant log-linear correlations were observed
      between physicochemical properties of PBDEs and their soil/moss (moss/dung)
      quotients.

PMID- 25965291
TI  - Recovering Magnetic Fe3O4-ZnO Nanocomposites from Algal Biomass Based on
      Hydrophobicity Shift under UV Irradiation.
AB  - Magnetic separation, one of the promising bioseparation technologies, faces the
      challenges in recovery and reuse of magnetic agents during algal harvesting for
      biofuel extraction. This study synthesized a steric acid (SA)-coated Fe3O4-ZnO
      nanocomposite that could shift hydrophobicity under UV365 irradiation. Our
      results showed that with the transition of surface hydrophobicity under UV365
      irradiation, magnetic nanocomposites detached from the concentrated algal
      biomass. The detachment was partially induced by the oxidation of SA coating
      layers due to the generation of radicals (e.g., *OH) by ZnO under UV365
      illumination. Consequently, the nanocomposite surface shifted from hydrophobic to
      hydrophilic, which significantly reduced the adhesion between magnetic particles
      and algae as predicted by the extended Derjaguin and Landau, Verwey, and Overbeek
      (EDLVO) theory. Such unique hydrophobicity shift may also find many other
      potential applications that require recovery, recycle, and reuse of valuable
      nanomaterials to increase sustainability and economically viability.

PMID- 25965293
TI  - Preparation of Tunable (BaSrMg)O for Oxygen Chemisorption: Formation Mechanism
      and Characterization.
AB  - Composition-tunable single-phase three-component alkaline earth oxide of
      (BaSrMg)O was prepared based on the consecutive precipitation and thermal
      decomposition of (BaSrMg)CO3. First, the single-phase (BaSrMg)CO3 was
      coprecipitated via ion self-assembly, phase-transformation, and agglomeration.
      The element composition of (BaSrMg)CO3 could be simply tuned by the composition
      of the reactants. Then, (BaSrMg)CO3 was converted to (BaSrMg)O under an H2
      atmosphere at 750  degrees C. This (BaSrMg)O showed fast chemisorption-desorption
      responses with oxygen chemisorption rate: t80 = 3.9 min and desorption rate: t80
      = 14 min and a high thermal stability for the redox reaction of BaO-BaO2. In
      addition, the chemisorption capacity of (BaSrMg)O (4.39% Sr composition) is ~1.92
      mmol/g, which is much higher than the chemisorption capacity of BaO/MgO at 1.75
      mmol/g (Jin et al., Ind. Eng. Chem. Res., 2005, 44, 2942), while the transient
      oxygen pressure for the redox reaction of (BaSrMg)O (4.39% Sr composition) was
      significantly enhanced from 76 to 135 mmHg due to the inclusion of Sr in
      (BaSrMg)O. The transient oxygen pressure could be further improved via adjusting
      the Sr composition in (BaSrMg)O. Consequently, the tunable (BaSrMg)O has a high
      potential as a chemisorbent for the industrial application of oxygen separation. 

PMID- 25965294
TI  - Development of a Serological Assay for the Sea Lion (Zalophus californianus)
      Anellovirus, ZcAV.
AB  - New diseases in marine animals are emerging at an increasing rate, yet
      methodological limitations hinder characterization of viral infections. Viral
      metagenomics is an effective method for identifying novel viruses in diseased
      animals; however, determining virus pathogenesis remains a challenge. A novel
      anellovirus (Zalophus californianus anellovirus, ZcAV) was recently reported in
      the lungs of captive California sea lions involved in a mortality event. ZcAV was
      not detected by PCR in the blood of these animals, creating the inability to
      assess the prevalence of ZcAV in live sea lions. This study developed an enzyme
      linked immunosorbent assay (ELISA) to detect antibodies to ZcAV in sea lion
      serum. To assess ZcAV prevalence, paired serum and lung samples (n = 96) from
      wild sea lions that stranded along the California coast were tested through ELISA
      and PCR, respectively. Over 50% of the samples tested positive for ZcAV by ELISA
      (34%), PCR (29%), or both (11%) assays. ZcAV is prevalent in stranded wild sea
      lion populations and results suggest that PCR assays alone may grossly
      underestimate ZcAV exposure. This ELISA provides a tool for testing live sea
      lions for ZcAV exposure and is valuable for subsequent studies evaluating the
      potential pathogenicity of this anellovirus. 

PMID- 25965297
TI  - An ultrarobust high-performance triboelectric nanogenerator based on charge
      replenishment.
AB  - Harvesting ambient mechanical energy is a green route in obtaining clean and
      sustainable electric energy. Here, we report an ultrarobust high-performance
      triboelectric nanogenerator (TENG) on the basis of charge replenishment by
      creatively introducing a rod rolling friction in the structure design. With a
      grating number of 30 and a free-standing gap of 0.5 mm, the fabricated TENG can
      deliver an output power of 250 mW/m(2) at a rotating rate of 1000 r/min. And it
      is capable of charging a 200 MUF commercial capacitor to 120 V in 170 s, lighting
      up a G16 globe light as well as 16 spot lights connected in parallel. Moreover,
      the reported TENG holds an unprecedented robustness in harvesting rotational
      kinetic energy. After a continuous rotation of more than 14.4 million cycles,
      there is no observable electric output degradation. Given the superior output
      performance together with the unprecedented device robustness resulting from
      distinctive mechanism and novel structure design, the reported TENG renders an
      effective and sustainable technology for ambient mechanical energy harvesting.
      This work is a solid step in the development toward TENG-based self-sustained
      electronics and systems. 

PMID- 25965295
TI  - Low-cost photodynamic therapy devices for global health settings:
      Characterization of battery-powered LED performance and smartphone imaging in 3D
      tumor models.
AB  - A lack of access to effective cancer therapeutics in resource-limited settings is
      implicated in global cancer health disparities between developed and developing
      countries. Photodynamic therapy (PDT) is a light-based treatment modality that
      has exhibited safety and efficacy in the clinic using wavelengths and irradiances
      achievable with light-emitting diodes (LEDs) operated on battery power. Here we
      assess low-cost enabling technology to extend the clinical benefit of PDT to
      regions with little or no access to electricity or medical infrastructure. We
      demonstrate the efficacy of a device based on a 635 nm high-output LED powered by
      three AA disposable alkaline batteries, to achieve strong cytotoxic response in
      monolayer and 3D cultures of A431 squamous carcinoma cells following
      photosensitization by administering aminolevulinic acid (ALA) to induce the
      accumulation of protoporphyrin IX (PpIX). Here we characterize challenges of
      battery-operated device performance, including battery drain and voltage
      stability specifically over relevant PDT dose parameters. Further motivated by
      the well-established capacity of PDT photosensitizers to serve as tumour
      selective fluorescence contrast agents, we demonstrate the capability of a
      consumer smartphone with low-cost add-ons to measure concentration-dependent PpIX
      fluorescence. This study lays the groundwork for the on-going development of
      image-guided ALA-PDT treatment technologies for global health applications. 

PMID- 25965300
TI  - Defect Control and n-Doping of Encapsulated Graphene by Helium-Ion-Beam
      Irradiation.
AB  - We study with Raman spectroscopy the influences of He(+) bombardment and the
      environment on beam-induced defects in graphene encapsulated in hexagonal boron
      nitride (h-BN). We show for the first time experimentally the autonomous behavior
      of the D' defect Raman peak: in contrast to the D defect peak, the D' defect peak
      is sensitive to the local environment. In particular, it saturates with ion dose
      in the encapsulated graphene. Electrical measurements reveal n-type conduction in
      the BN-encapsulated graphene. We conclude that unbound atoms ("interfacials")
      between the sp(2)-layers of graphene and h-BN promote self-healing of the beam
      induced lattice damage and that nitrogen-carbon exchange leads to n-doping of
      graphene. 

PMID- 25965298
TI  - Revisiting the transcriptional analysis of primary tumours and associated nodal
      metastases with enhanced biological and statistical controls: application to
      thyroid cancer.
AB  - BACKGROUND: Transcriptome profiling has helped characterise nodal spread. The
      interpretation of these data, however, is not without ambiguities. METHODS: We
      profiled the transcriptomes of papillary thyroid cancer nodal metastases,
      associated primary tumours and primary tumours from N0 patients. We also included
      patient-matched non-cancerous thyroid and lymph node samples as controls to
      address some limits of previous studies. RESULTS: The transcriptomes of patient
      matched primary tumours and metastases were more similar than those of unrelated
      metastases/primary pairs, as previously reported in other organ systems. This
      similarity partly reflected patient background. Lymphoid tissues in the
      metastases confounded the comparison of patient-matched primary tumours and
      metastases. We circumvented this with an original data adjustment, revealing a
      differential expression of stroma-related gene signatures also regulated in other
      organs. The comparison of N0 vs N+ primary tumours uncovered a signal
      irreproducible across independent data sets. This signal was also detectable when
      comparing the non-cancerous thyroid tissues adjacent to N0 and N+ tumours,
      suggesting a cohort-specific bias also likely present in previous similarly sized
      studies. Classification of N0 vs N+ yielded an accuracy of 63%, but additional
      statistical controls absent in previous studies revealed that this is explainable
      by chance alone. We used large data sets from The Cancer Genome Atlas: N0 vs N+
      classification was not better than random for most cancers. Yet, it was
      significant, but of limited accuracy (<70%) for thyroid, breast and head and neck
      cancers. CONCLUSIONS: The clinical potential of gene expression to predict nodal
      metastases seems limited for most cancers.

PMID- 25965299
TI  - Redox signalling to nuclear regulatory proteins by reactive oxygen species
      contributes to oestrogen-induced growth of breast cancer cells.
AB  - BACKGROUND: 17beta-Oestradiol (E2)-induced reactive oxygen species (ROS) have
      been implicated in regulating the growth of breast cancer cells. However, the
      underlying mechanism of this is not clear. Here we show how ROS through a novel
      redox signalling pathway involving nuclear respiratory factor-1 (NRF-1) and p27
      contribute to E2-induced growth of MCF-7 breast cancer cells. METHODS: Chromatin
      immunoprecipitation, qPCR, mass spectrometry, redox western blot, colony
      formation, cell proliferation, ROS assay, and immunofluorescence microscopy were
      used to study the role of NRF-1. RESULTS: The major novel finding of this study
      is the demonstration of oxidative modification of phosphatases PTEN and CDC25A by
      E2-generated ROS along with the subsequent activation of AKT and ERK pathways
      that culminated in the activation of NRF-1 leading to the upregulation of cell
      cycle genes. 17beta-Oestradiol-induced ROS by influencing nuclear proteins p27
      and Jab1 also contributed to the growth of MCF-7 cells. CONCLUSIONS: Taken
      together, our results present evidence in the support of E2-induced ROS-mediated
      AKT signalling leading to the activation of NRF-1-regulated cell cycle genes as
      well as the impairment of p27 activity, which is presumably necessary for the
      growth of MCF-7 cells. These observations are important because they provide a
      new paradigm by which oestrogen may contribute to the growth of breast cancer.

PMID- 25965301
TI  - Phase stability in nanoscale material systems: extension from bulk phase
      diagrams.
AB  - Phase diagrams of multi-component systems are critical for the development and
      engineering of material alloys for all technological applications. At nano
      dimensions, surfaces (and interfaces) play a significant role in changing
      equilibrium thermodynamics and phase stability. In this work, it is shown that
      these surfaces at small dimensions affect the relative equilibrium thermodynamics
      of the different phases. The CALPHAD approach for material surfaces (also termed
      "nano-CALPHAD") is employed to investigate these changes in three binary systems
      by calculating their phase diagrams at nano dimensions and comparing them with
      their bulk counterparts. The surface energy contribution, which is the dominant
      factor in causing these changes, is evaluated using the spherical particle
      approximation. It is first validated with the Au-Si system for which experimental
      data on phase stability of spherical nano-sized particles is available, and then
      extended to calculate phase diagrams of similarly sized particles of Ge-Si and Al
      Cu. Additionally, the surface energies of the associated compounds are calculated
      using DFT, and integrated into the thermodynamic model of the respective binary
      systems. In this work we found changes in miscibilities, reaction compositions of
      about 5 at%, and solubility temperatures ranging from 100-200 K for particles of
      sizes 5 nm, indicating the importance of phase equilibrium analysis at nano
      dimensions. 

PMID- 25965302
TI  - Expansion of the 'Reticulosphere': Diversity of Novel Branching and Network
      forming Amoebae Helps to Define Variosea (Amoebozoa).
AB  - Amoebae able to form cytoplasmic networks or displaying a multiply branching
      morphology remain very poorly studied. We sequenced the small-subunit ribosomal
      RNA gene of 15 new amoeboid isolates, 14 of which are branching or network
      forming amoebae (BNFA). Phylogenetic analyses showed that these isolates all
      group within the poorly-known and weakly-defined class Variosea (Amoebozoa). They
      are resolved into six lineages corresponding to distinct new morphotypes; we
      describe them as new genera Angulamoeba (type species Angulamoeba
      microcystivorans n. gen., n. sp.; and A. fungorum n. sp.), Arboramoeba (type
      species Arboramoeba reticulata n. gen., n. sp.), Darbyshirella (type species
      Darbyshirella terrestris n. gen., n. sp.), Dictyamoeba (type species Dictyamoeba
      vorax n. gen., n. sp.), Heliamoeba (type species Heliamoeba mirabilis n. gen., n.
      sp.), and Ischnamoeba (type species Ischnamoeba montana n. gen., n. sp.). We also
      isolated and sequenced four additional variosean strains, one belonging to
      Flamella, one related to Telaepolella tubasferens, and two members of the
      cavosteliid protosteloid lineage. We identified a further 104 putative variosean
      environmental clone sequences in GenBank, comprising up to 14 lineages that may
      prove to represent additional novel morphotypes. We show that BNFA are
      phylogenetically widespread in Variosea and morphologically very variable, both
      within and between lineages. 

PMID- 25965303
TI  - Comparison between fingerprints of the epidermis and dermis: Perspectives in the
      identifying of corpses.
AB  - In forensic science, the putrefaction, maceration, mummification or burning make
      it difficult to collect the fingerprints of the epidermis for identification
      purposes. In such cases, the comparison between fingerprints collected from the
      dermal surface and the ante mortem pattern of the epidermal surface archived in
      databases must be performed. Therefore, considering that the identification of
      corpses is done by comparison of fingerprints on different surfaces, this study
      aimed to compare the epidermal and the dermal fingerprints to determine the
      discrepancies between the minutiae of both surfaces. The study was conducted with
      excised fingers of 19 fresh adult corpses. Once selected, excised and
      photographed, the fingers were subjected to maceration with 0.5% acetic acid
      solution for the removal of the epidermal glove and for registering the dermal
      fingerprint. Then, an area of 1cm(2) in the epidermal and dermal photographies
      was selected and the minutiae of each were separately marked by an expert in
      identification. The comparison between minutiae of the epidermal and dermal
      surfaces showed that: (1) both surfaces maintained the patterns and
      characteristics of fingerprints (arch, whorl or loop) and the characteristics
      related to the systems and the disposal of the lines, meaning the formation or
      not of deltas; (2) the total number of marked minutiae did not differ between
      both surfaces for the group of individuals (paired t test, p=0.48); (3) the
      percentage of coincidences and divergences (minutiae present on only one surface)
      between minutiae were 63.0+/-20.0% and 37.0+/-20.0%, respectively; (4)
      identification was possible for 16 fingers/individuals, but not for 3 of them;
      (5) the increase in the number of marked minutiae does not affect the percentage
      of coincidences. Our results demonstrate the feasibility of the dermal surface
      for identification purposes due to the high percentage of matching minutiae, but
      considering the discrepancies and the inconclusive identification of 3
      fingers/individuals, our study points to the use of more fingers per individual,
      as well as the possibility of further studies to improve on the techniques for
      increasing the identification of corpses, or even to deploy new technologies to
      ensure their rapid and safe identification. 

PMID- 25965304
TI  - A facial reconstruction and identification technique for seriously devastating
      head wounds.
AB  - Many authors have focused on facial identification techniques, and facial
      reconstructions for cases when skulls have been found are especially well known.
      However, a standardized facial identification technique for an unknown body with
      seriously devastating head injuries has not yet been developed. A reconstruction
      and identification technique was used in 7 cases of accidents involving trains
      striking pedestrians. This identification technique is based on the removal of
      skull bone fragments, subsequent fixation of soft tissue onto a universal
      commercial polystyrene head model, precise suture of dermatomuscular flaps, and
      definitive adjustment using cosmetic treatments. After reconstruction,
      identifying marks such as scars, eyebrows, facial lines, facial hair and partly
      hairstyle become evident. It is then possible to present a modified picture of
      the reconstructed face to relatives. After comparing the results with photos of
      the person before death, this technique has proven to be very useful for
      identifying unknown bodies when other identification techniques are not
      available. This technique is useful for its being rather quick and especially for
      its results. 

PMID- 25965305
TI  - Rapid detection of NBOME's and other NPS on blotter papers by direct ATR-FTIR
      spectrometry.
AB  - Blotter paper is among the most common forms of consumption of new psychotropic
      substances (NPS), formerly referred as designer drugs. In many cases, users are
      misled to believe they are taking LSD when, in fact, they are taking newer and
      less known drugs like the NBOMEs or other substituted phenethylamines. We report
      our findings in quick testing of blotter papers for illicit substances like
      NBOMEs and other NPS by taking ATR-FTIR spectra directly from blotters seized on
      the streets, without any sample preparation. Both sides (front and back) of each
      blotter were tested. Collected data were analyzed by single- and multi-component
      spectral matching and submitted to chemometric discriminant analysis. Our results
      showed that, on 66.7% of the cases analyzed, seized blotters contained one or
      more types of NBOMEs, confirming the growing presence of this novel substances on
      the market. Matching IR signals were detected on both or just one side of the
      blotters and showed variable strength. Although no quantitative analysis was
      made, detection of these substances by the proposed approach serves as indication
      of variable and possibly higher dosages per blotter when compared to LSD, which
      showed to be below the detection limit of the applied method. Blotters containing
      a mescaline-like compound, later confirmed by GC-MS and LC-MS to be MAL
      (methallylescaline), a substance very similar to mescaline, were detected among
      the samples tested. Validity of direct ATR-FTIR testing was confirmed by checking
      the obtained results against independent GC-MS or LC-MS results for the same
      cases/samples. 

PMID- 25965306
TI  - GC-MS studies on the six naphthoyl-substituted 1-n-pentyl-indoles: JWH-018 and
      five regioisomeric equivalents.
AB  - The GC-MS properties of the synthetic cannabinoid drug of abuse 3-(1-naphthoyl)-1
      pentylindole (JWH-018) and all 5 of its' regioisomeric 1-naphthoyl substituted 1
      n-pentylindoles are compared in this report. These compounds have the 1-naphthoyl
      group attached at each of the possible substituent positions of the indole ring.
      The six compounds have the same elemental composition C24H23NO and the same
      substituents attached to the indole ring. The electron ionization mass spectra
      showed equivalent regioisomeric major fragment ions resulting from cleavage of
      the groups attached to the central indole nucleus. The characteristic (M-17)(+)
      fragment ion at m/z 324 resulting from the loss of an OH group was significant in
      the EI-MS of 3-, 4-, 5- and 6-(1-naphthoyl)-1-pentylindole. Fragment ions
      occurred at m/z 127 and 155 for the naphthyl and naphthoyl cations common to all
      six regioisomeric substances. Indole containing fragments produced the cations at
      m/z 284, 270, 214 and 186. The unique fragment at m/z 141 observed in the 1,2-
      and 1,7-isomers resulted from a rearrangement involving the two indole
      substituents to yield the C10H7CH2(+) cation. The major points of EI-MS
      differentiation of the synthetic cannabinoid JWH-018 from the other five isomers
      are the high relative abundance of both the m/z 144 ion and the m/z 324 ion in
      the JWH-018 spectrum. GC separations on a capillary column containing a
      trifluoropropyl methyl polysiloxane (Rtx-200) stationary phase provided excellent
      resolution of these six compounds. The elution order appears related to the
      relative distance between the two indole substituents with the lowest retention
      associated with minimum distance between the groups attached to the indole
      nucleus. 

PMID- 25965307
TI  - Shedding light on sunscreen biosynthesis in zebrafish.

PMID- 25965308
TI  - CROI 2015: Basic Science Review.
AB  - The 2015 Conference on Retroviruses and Opportunistic Infections (CROI)
      represents a forum that encompasses all facets of research on HIV/AIDS and its
      complications. CROI is a valuable venue for scientific and public health
      researchers, clinicians, policy makers, and community representatives to be
      updated on the latest advances in their specific areas of interest and beyond.
      CROI 2015 continued to surprise. New insights into the viral reservoirs that
      persist in the face of antiretroviral therapy were prominently featured, as were
      therapeutic approaches aimed at curtailing and eliminating persistent viral
      reservoirs in HIV-infected individuals. Basic science is providing surrogates
      that could be valuable in how viral reservoirs are measured and, ultimately, in
      how to gauge if they are being effectively eliminated. 

PMID- 25965309
TI  - CROI 2015: Advances in HIV Testing and Prevention Strategies.
AB  - HIV testing rates and awareness of HIV serostatus have improved globally, but
      disparities continue between black and white men who have sex with men (MSM) in
      the United States, and between women and men globally. The 2015 Conference on
      Retroviruses and Opportunistic Infections (CROI) was a watershed moment for
      preexposure prophylaxis (PrEP). Two efficacy trials conducted in MSM were stopped
      early because of an 86% reduction in the risk of HIV acquisition among men taking
      tenofovir and emtricitabine. New drugs, long-acting formulations, and different
      patterns of dosing are undergoing evaluation. Poor adherence has limited PrEP
      effectiveness in some populations, and new measures of drug levels in dried blood
      spots and hair appear to be promising new tools. Pharmacokinetic differences of
      PrEP agents in rectal versus vaginal tissue preclude extrapolating PrEP trial
      results among MSM to women. Several studies reported no HIV transmissions between
      HIV-serodiscordant couples when the seropositive partner was successfully treated
      for 6 months. However, consistent viral suppression does not occur in a
      substantial minority of patients in many clinics, reducing the potential impact
      of treatment as prevention. 

PMID- 25965310
TI  - CROI 2015: Advances in Antiretroviral Therapy.
AB  - The 2015 Conference on Retroviruses and Opportunistic Infections included new and
      exciting advances in the realm of antiretroviral therapy. The Temprano trial
      demonstrated benefits from early antiretroviral therapy and isoniazid preventive
      therapy. Important data on investigational antiretroviral drugs were presented,
      including tenofovir alafenamide fumarate and BMS-955176, an HIV-1 maturation
      inhibitor. Novel data on the HIV care continuum from resource-rich and -limited
      settings highlighted persistent sex- and race-related disparities in care
      engagement, and the crucial need to bring HIV testing and care into the community
      to improve engagement across the care continuum. Life expectancy data from
      resource-limited settings reveal dramatic improvements across sub-Saharan Africa,
      although people with HIV still live 5 years to 10 years less than those without
      HIV, and new cost-effectiveness research revealed that the price of
      antiretroviral therapy itself remains a key driver of cost and cost-effectiveness
      calculations. Results from the PROMISE trial showed reduced rates of mother-to
      child transmission among women who received antiretroviral therapy with 3 drugs
      compared with women who received zidovudine monotherapy, supporting current World
      Health Organization guidelines. 

PMID- 25965311
TI  - CROI 2015: Neurologic Complications of HIV Infection.
AB  - More than 30 years into the HIV epidemic, research efforts are focusing on better
      understanding how the central nervous system (CNS) is adversely affected by HIV
      and on improving the quality of life of HIV-infected individuals. At the 2015
      Conference on Retroviruses and Opportunistic Infections, neurologic presentations
      concentrated on characterization of potential CNS reservoirs of HIV, the
      pathogenesis of HIV-associated neurocognitive disorders (HAND), diagnosis of
      cognitive dysfunction caused by HIV,neuroimaging biomarkers of HAND, and
      treatment of modifiable risk factors of HAND. Studies presented also highlighted
      research on CNS disorders in international, resource-limited settings, setting
      the stage for a growing collection of collaborative studies that will directly
      impact the largest concentrations of people living with HIV worldwide. 

PMID- 25965312
TI  - CROI 2015: Complications of HIV Infection and Antiretroviral Therapy.
AB  - Noncommunicable diseases, such as cardiovascular disease, hypertension, renal and
      bone disease, and malignancies are an ongoing concern during the course of
      treated HIV disease. Research in this area continues to focus on the epidemiology
      and risk factors associated with these conditions, identifying the contributions
      of HIV-related immunopathology to specific and collective end-organ diseases, and
      evaluating interventions to prevent or reduce the morbidity associated with these
      conditions. Infectious complications of HIV, such as tuberculosis and
      cryptococcal disease, also continue to cause substantial morbidity and mortality;
      diagnosis, prevention, and treatment of these is an area of focus. The 2015
      Conference on Retroviruses and Opportunistic Infections provided new insights
      into all of these areas. 

PMID- 25965314
TI  - Structure of nanorod assembly in the gyroid phase of diblock copolymer.
AB  - Diblock copolymers undergo microphase separation to form various microstructures,
      for example, lamellar, gyroid, cylindrical, cubic phases depending on composition
      and segregation strength (Flory-Huggins parameter chi). Thus, it can act as
      template to organize doped nanomaterials into different 3D self-assembled
      structures located within the block copolymer matrix. Gyroid phase is one of the
      microstructures formed by block copolymer. It has a curved interfacial surface
      providing confinements throughout the matrix and thus can regulate the shape and
      sizes of self-assembled nanorods doped in it. Mesoscale simulation of model
      systems has been performed to explore the structure and dynamics of self-assembly
      of bundles formed by nanorods of different flexibilities in the gyroid phase of
      diblock copolymer matrix. Bundles of different shapes and sizes have been found
      to be formed depending on the nanorod bending flexibility and copolymer-nanorod
      interactions. The shape anisotropy (kappa(2)) and radius of gyration (R(g)(2)) of
      bundles situated at different interfacial confining locations of block copolymer
      matrices have been investigated as a function of nanorod flexibility and nanorod
      diblock copolymer miscibility.

PMID- 25965313
TI  - CROI 2015: Highlights of Viral Hepatitis Therapy.
AB  - High cure rates with all-oral regimens for patients with HIV/hepatitis C virus
      (HCV) coinfection were a highlight of the 2015 Conference on Retroviruses and
      Opportunistic Infections. Twelve weeks of sofosbuvir and daclatasvir led to
      sustained virologic response (SVR) rates of 96% in treatment-naive and 98% in
      treatment-experienced HCV genotype 1-infected patients. Twelve weeks of
      sofosbuvir plus ledipasvir had similar results, with SVR rates of 95% in
      treatment-naive and 96% in treatment-experienced patients. Patients with
      cirrhosis were included in both trials and attained SVR rates of 92% to 94%. Real
      world performance of sofosbuvir and simeprevir resulted in SVR rates similar to
      those attained in clinical trials. Identifying HCV infection, linking patients to
      care, reducing barriers to drug access, and ensuring adherence will be key to
      realizing the enormous potential of high cure rates with interferon alfa-free
      therapies. Preventing reinfection after cure will be of particular importance in
      the HIV-infected population, which was highly impacted by reinfection rates of
      more than 20% during 5 years of follow-up in a meta-analysis. 

PMID- 25965316
TI  - Cracking the egg: An insight into egg hypersensitivity.
AB  - Hypersensitivity to the chicken egg is a widespread disorder mainly affecting 1
      2% of children worldwide. It is the second most common food allergy in children,
      next to cow's milk allergy. Egg allergy is mainly caused by hypersensitivity to
      four allergens found in the egg white; ovomucoid, ovalbumin, ovotransferrin and
      lysozyme. However, some research suggests the involvement of allergens
      exclusively found in the egg yolk such as chicken serum albumin and YGP42, which
      may play a crucial role in the overall reaction. In egg allergic individuals,
      these allergens cause conditions such as itching, atopic dermatitis, bronchial
      asthma, vomiting, rhinitis, conjunctivitis, laryngeal oedema and chronic
      urticaria, and anaphylaxis. Currently there is no permanent cure for egg allergy.
      Upon positive diagnosis for egg allergy, strict dietary avoidance of eggs and
      products containing traces of eggs is the most effective way of avoiding future
      hypersensitivity reactions. However, it is difficult to fully avoid eggs since
      they are found in a range of processed food products. An understanding of the
      mechanisms of allergic reactions, egg allergens and their prevalence, egg allergy
      diagnosis and current treatment strategies are important for future studies. This
      review addresses these topics and discusses both egg white and egg yolk allergy
      as a whole.

PMID- 25965315
TI  - A broad range of mutations in HIV-1 neutralizing human monoclonal antibodies
      specific for V2, V3, and the CD4 binding site.
AB  - The HIV vaccine-induced neutralizing antibodies (Abs) display low rates of
      mutation in their variable regions. To determine the range of neutralization
      mediated by similar human monoclonal Abs (mAbs) but derived from unselected
      chronically HIV-1 infected subjects, we tested a panel of 66 mAbs specific to V3,
      CD4 binding site (CD4bs) and V2 regions. The mAbs were tested against 41
      pseudoviruses, including 15 tier 1 and 26 tier 2, 3 viruses, showing that the
      neutralization potency and breadth of anti-V3 mAbs were significantly higher than
      those of the anti-CD4bs and anti-V2 mAbs, and only anti-V3 mAbs were able to
      neutralize some tier 2, 3 viruses. The percentage of mutations in the variable
      regions of the heavy (VH) and light (VL) chains varied broadly in a range from 2%
      to 18% and correlated moderately with the neutralization breadth of tier 2, 3
      viruses. There was no correlation with neutralization of tier 1 viruses as some
      mAbs with low and high percentages of mutations neutralized the same number of
      viruses. The electrostatic interactions between anti-V3 mAbs and the charged V3
      region may contribute to their neutralization because the isoelectric points of
      the VH CDR3 of 48 anti-V3 mAbs were inversely correlated with the neutralization
      breadth of tier 2, 3 viruses. The results demonstrate that infection-induced
      antibodies to CD4bs, V3 and V2 regions can mediate cross-clade neutralization
      despite low levels of mutations which can be achieved by HIV-1 vaccine-induced
      antibodies.

PMID- 25965317
TI  - Luminescent Di- and Trinuclear Boron Complexes Based on Aromatic Iminopyrrolyl
      Spacer Ligands: Synthesis, Characterization, and Application in OLEDs.
AB  - New bis- and tris(iminopyrrole)-functionalized linear (1,2-(HNC4 H3 -C(H)?N)2 -C6
      H4 (2), 1,3-(HNC4 H3 -C(H)?N)2 -C6 H4 (3), 1,4-(HNC4 H3 -C(H)?N)2 -C6 H4 (4),
      4,4'-(HNC4 H3 -C(H)?N)2 -(C6 H4 -C6 H4 ) (5), 1,5-(HNC4 H3 C-(H)?N)2 -C10 H6 (6),
      2,6-(HNC4 H3 C-(H)?N)2 -C10 H6 (7), 2,6-(HNC4 H3 C-(H)?N)2 -C14 H8 (8)) and star
      shaped (1,3,5-(HNC4 H3 -C(H)?N-1,4-C6 H4 )3 -C6 H3 (9)) pi-conjugated molecules
      were synthesized by the condensation reactions of 2-formylpyrrole (1) with
      several aromatic di- and triamines. The corresponding linear diboron chelate
      complexes (Ph2 B[1,3-bis(iminopyrrolyl)-phenyl]BPh2 (10), Ph2 B[1,4
      bis(iminopyrrolyl)-phenyl]BPh2 (11), Ph2 B[4,4'-bis(iminopyrrolyl)-biphenyl]BPh2
      (12), Ph2 B[1,5-bis(iminopyrrolyl)-naphthyl]BPh2 (13), Ph2 B[2,6
      bis(iminopyrrolyl)-naphthyl]BPh2 (14), Ph2 B[2,6-bis(iminopyrrolyl)
      anthracenyl]BPh2 (15)) and the star-shaped triboron complex ([4',4'',4'''
      tris(iminopyrrolyl)-1,3,5-triphenylbenzene](BPh2 )3 (16)) were obtained in
      moderate to good yields, by the treatment of 3-9 with B(C6 H5 )3 . The ligand
      precursors are non-emissive, whereas most of their boron complexes are highly
      fluorescent; their emission color depends on the pi-conjugation length. The
      photophysical properties of the luminescent polyboron compounds were measured,
      showing good solution fluorescence quantum yields ranging from 0.15 to 0.69. DFT
      and time-dependent DFT calculations confirmed that molecules 10 and 16 are blue
      emitters, because only one of the iminopyrrolyl groups becomes planar in the
      singlet excited state, whereas the second (and third) keeps the same geometry.
      Compound 13, in which planarity is not achieved in any of the groups, is poorly
      emissive. In the other examples (11, 12, 14, and 15), the LUMO is stabilized,
      narrowing the gap between the highest occupied molecular orbital and the lowest
      unoccupied molecular orbital (HOMO-LUMO), and the two iminopyrrolyl groups become
      planar, extending the size of the pi-system, to afford green to yellow emissions.
      Organic light-emitting diodes (OLEDs) were fabricated by using the new polyboron
      complexes and their luminance was found to be in the order of 2400 cd m(-2) , for
      single layer devices, increasing to 4400 cd m(-2) when a hole-transporting layer
      is used. 

PMID- 25965318
TI  - Facile Synthesis of Prussian Blue Derivate-Modified Mesoporous Material via
      Photoinitiated Thiol-Ene Click Reaction for Cesium Adsorption.
AB  - A novel strategy to synthesize a functional mesoporous material for efficient
      removal of cesium is reported. Specifically, Prussian blue derivate-modified SBA
      15 (SBA-15@FC) was prepared by photoinitiated thiol-ene reaction between thiol
      modified SBA-15 and pentacyano(4-vinyl pyridine)ferrate complex. The effects of
      weight percentage of the Prussian blue derivate, pH, adsorbent dose, co-existing
      ions, and initial concentration were evaluated on the adsorption of cesium ions.
      The adsorption kinetically follows a pseudo-second-order model and reaches
      equilibrium within 2 h with a high adsorption capacity of about 13.90 mg Cs g(-1)
      , which indicates that SBA-15@FC is a promising adsorbent to effectively remove
      cesium from aqueous solutions. 

PMID- 25965319
TI  - Mechanical temporal fluctuation induced distance and force systematic errors in
      Casimir force experiments.
AB  - The basic theory of temporal mechanical fluctuation induced systematic errors in
      Casimir force experiments is developed and applications of this theory to several
      experiments is reviewed. This class of systematic error enters in a manner
      similar to the usual surface roughness correction, but unlike the treatment of
      surface roughness for which an exact result requires an electromagnetic mode
      analysis, time dependent fluctuations can be treated exactly, assuming the
      fluctuation times are much longer than the zero point and thermal fluctuation
      correlation times of the electromagnetic field between the plates. An
      experimental method for measuring absolute distance with high bandwidth is also
      described and measurement data presented. 

PMID- 25965320
TI  - Erratum.

PMID- 25965321
TI  - A comparative effectiveness analysis of treatment for latent tuberculosis
      infection using multilevel selection models.
AB  - AIM: Nine months of isoniazid (9INH) is the gold standard for treatment of latent
      tuberculosis infection (LTBI). This paper compares the effectiveness of 9 months
      of isoniazid with 4 months of transitional rifampin (9H4R) to alternative
      therapies, including 9INH, 6 months of isoniazid (6INH) and 6 months of isoniazid
      with 4 months of transitional rifampin (6H4R), for treatment of LTBI. MATERIALS &
      METHODS: Using an ethnically diverse clinic sample of 552 patients given
      treatment for LTBI with 9H4R, we use multilevel selection models to examine the
      adjusted comparative effectiveness of the regimens among ethnic groups that
      feature distinct genetic predispositions to side effects on INH. For
      unadjusted/absolute effectiveness, we simulated cost-effectiveness ratios for 4
      months of rifampin (4RIF) and compared with bootstrapped confidence intervals for
      the alternative therapies. RESULTS: There are variations in the comparative
      effectiveness across ethnic groups, with the most notable differences for 9H4R.
      For unadjusted/absolute effectiveness, 4RIF presents the greatest net benefit for
      US born black and African patients. For all other ethnic groups, 6H4R was the
      most effective. CONCLUSION: Patient ethnicity affects tolerance to INH. 9H4R was
      the most effective LTBI treatment for all ethnicities. However, this result
      heavily depends on whether adjustments are made for self-selection.

PMID- 25965322
TI  - Identifying Health and Safety Concerns in Southeast Asian Immigrant Nail Salon
      Workers.
AB  - Nail salon workers are exposed to a variety of toxic chemicals at levels that
      remain unreported and have undetermined health consequences. The objective of the
      study was to gather information about the hazards in nail salons along with
      safety practices and health concerns of nail salon workers. A survey was
      conducted on 65 nail salon workers who were immigrants from Southeast Asia in
      Oregon, USA. More than 20% of the participants reported nose irritation and
      allergies as the most common health problems. Rare and no use of gloves and mask
      were reported among 72% and 32% of the participants, respectively. A
      significantly higher number of participants with "fair" or "poor" self-reported
      general health condition was found among the workers who applied acrylic nails
      compared with those who were not involved in this application. Findings of the
      study emphasize the need for more research to determine the relationship between
      chemical exposures in nail salons and health outcomes. 

PMID- 25965323
TI  - Bone marrow-derived stromal cells are more beneficial cell sources for tooth
      regeneration compared with adipose-derived stromal cells.
AB  - Tooth loss is presently a global epidemic and tooth regeneration is thought to be
      a feasible and ideal treatment approach. Choice of cell source is a primary
      concern in tooth regeneration. In this study, the odontogenic differentiation
      potential of two non-dental-derived stem cells, adipose-derived stromal cells
      (ADSCs) and bone marrow-derived stromal cells (BMSCs), were evaluated both in
      vitro and in vivo. ADSCs and BMSCs were induced in vitro in the presence of tooth
      germ cell-conditioned medium (TGC-CM) prior to implantation into the omentum
      majus of rats, in combination with inactivated dentin matrix (IDM). Real-time
      quantitative polymerase chain reaction (RT-qPCR) was used to detect the mRNA
      expression levels of odontogenic-related genes. Immunofluorescence and
      immunohistochemical assays were used to detect the protein levels of odontogenic
      specific genes, such as DSP and DMP-1 both in vitro and in vivo. The results
      suggest that both ADSCs and BMSCs have odontogenic differentiation potential.
      However, the odontogenic potential of BMSCs was greater compared with ADSCs,
      showing that BMSCs are a more appropriate cell source for tooth regeneration. 

PMID- 25965324
TI  - "Zwitterionic Proton Sponge" Hydrogen Bonding Investigations on the Basis of Car
      Parrinello Molecular Dynamics.
AB  - 1,8-Bis(dimethylamino)-4,5-dihydroxynaphthalene has been investigated on the
      basis of static DFT computations and Car-Parrinello molecular dynamics. The
      simulations were performed in the gas phase and in the solid state. The studied
      "zwitterionic proton sponge" possesses two, short intramolecular hydrogen bonds
      (O-H...O and N-H...N) classified as Low Barrier Hydrogen Bonds (LBHBs);
      therefore, the system studied is strongly anharmonic. In addition, the compound
      exists as a "zwitterion" in solution and in the solid state, thus the
      intramolecular hydrogen bonds belong to the class of charge-assisted
      interactions. The applied quantum-chemical methods enabled investigations of
      metric and spectroscopic parameters of the molecule. The time-evolution
      investigations of the H-bonding showed a strong delocalization of the bridge
      protons and their high mobility, reflected in the low barriers on the free energy
      surfaces. Frequent proton transfer phenomena were noticed. The power spectra of
      atomic velocity were computed to analyze the vibrational features associated with
      O-H and N-H stretching. A broad absorption was indicated for both hydrogen
      bridges. For the first time, Car-Parrinello molecular dynamics results are
      reported for the compound, and they indicate a broad, shallow but not
      barrierless, potential well for each of the bridge protons. 

PMID- 25965325
TI  - Scope and Limitations of the Liebeskind-Srogl Cross-Coupling Reactions Involving
      the Biellmann BODIPY.
AB  - Several new examples of meso-(het)arylBODIPY were prepared via the Liebeskind
      Srogl (L-S) cross-coupling reaction of the Biellmann BODIPYs (1a,b) and aryl- and
      heteroarylboronic acids in good to excellent yield. It was shown that this
      reaction could be carried out under microwave heating to shorten reaction times
      and/or increase the yield. It was illustrated that organostannanes also
      participate in the L-S reaction to give the corresponding BODIPY analogues in
      short reaction times and also with good to excellent yields. We analyze the role
      of the substituent at the sensitive meso position in the photophysical signatures
      of these compounds. In particular, the rotational motion of the aryl ring and the
      electron donor ability of the anchored moieties rule the nonradiative pathways
      and, hence, have a deep impact in the fluorescence efficiency. 

PMID- 25965326
TI  - Crystal Structure of Okadaic Acid Binding Protein 2.1: A Sponge Protein
      Implicated in Cytotoxin Accumulation.
AB  - Okadaic acid (OA) is a marine polyether cytotoxin that was first isolated from
      the marine sponge Halichondria okadai. OA is a potent inhibitor of protein
      serine/threonine phosphatases (PP) 1 and 2A, and the structural basis of
      phosphatase inhibition has been well investigated. However, the role and
      mechanism of OA retention in the marine sponge have remained elusive. We have
      solved the crystal structure of okadaic acid binding protein 2.1 (OABP2.1)
      isolated from H. okadai; it has strong affinity for OA and limited sequence
      homology to other proteins. The structure revealed that OABP2.1 consists of two
      alpha-helical domains, with the OA molecule deeply buried inside the protein. In
      addition, the global fold of OABP2.1 was unexpectedly similar to that of
      aequorin, a jellyfish photoprotein. The presence of structural homologues
      suggested that, by using similar protein scaffolds, marine invertebrates have
      developed diverse survival systems adapted to their living environments. 

PMID- 25965327
TI  - Efficient synthesis of cytidine diphosphate choline (CDP-choline) and its
      analogs.
AB  - An efficient P(V)-N activation approach for the synthesis of cytidine diphosphate
      choline (CDP-choline) and related ribo- and deoxyribonucleotide analogs has been
      established. 

PMID- 25965328
TI  - Design and Synthesis of Triazole-Linked xylo-Nucleoside Dimers.
AB  - Three triazole-linked nonionic xylo-nucleoside dimers T(L)-t-T(xL), T(L)-t
      A(BzxL) and T(L)-t-C(BzxL) have been synthesized for the first time by Cu(I)
      catalyzed azide-alkyne [3 + 2] cycloaddition reaction (CuAAC) of 1-(3'-azido-3'
      deoxy-2'-O,4'-C-methylene-beta-D-ribo-furanosyl)thymine with different alkynes,
      i.e., 1-(5'-deoxy-5'-C-ethynyl-2'-O,4'-C-methylene-beta-D-xylofuranosyl)thymine,
      9-(5'-deoxy-5'-C-ethynyl-2'-O,4'-C-methylene-beta-D-xylo-furanosyl)-N6
      benzoyladenine and 1-(5'-deoxy-5'-C-ethynyl-2'-O,4'-C-methylene-beta-D
      xylofuranosyl)-N4-benzoylcytosine in 90%-92% yields. Among the two Cu(I)
      reagents, CuSO4.5H2O-sodium ascorbate in THF:(t)BuOH:H2O (1:1:1) and CuBr.SMe2 in
      THF used for cycloaddition (click) reaction, the former one was found to be
      better yielding than the latter one.

PMID- 25965329
TI  - The Risk of the Preparation of Artificial DNAs via an Interrupted Automated Solid
      Phase Triester Method.
AB  - In this paper, the risk of the preparation of artificial DNAs via an interrupted
      automated solid-phase triester procedure is discussed. These results differ
      completely from the corresponding results obtained by a gradual non-automated
      synthesis, indicated as solution-phase chemistry. With experimental results
      focused on model systems under various conditions and molecular-mechanics
      calculations, it feels as a challenge to offer an explanation for this different
      behavior. Attention is briefly given to click-linked DNA fragments as a
      substitute of phosphate linkages. 

PMID- 25965330
TI  - Enzymatic synthesis of 2'-ara and 2'-deoxy analogues of c-di-GMP.
AB  - The substrate specificity of recombinant full-length diguanylate cyclase (DGC) of
      Thermotoga maritima with mutant allosteric site was investigated. It has been
      originally shown that the enzyme could use GTP closest analogues - 2'
      deoxyguanosine-5'-triphosphate (dGTP) and 9-beta-D-arabinofuranosyl-guanine-5'
      triphosphate (araGTP) as the substrates. The first demonstrations of an enzymatic
      synthesis of bis-(3'-5')-cyclic dimeric deoxyguanosine monophosphate (c-di-dGMP)
      and the previously unknown bis-(3'-5')-cyclic dimeric araguanosine monophosphate
      (c-di-araGMP) using DGC of T. maritima in the form of inclusion bodies have been
      provided. 

PMID- 25965331
TI  - DNA duplex stability of the thio-iso-guanine*methyl-iso-Cytosine base pair.
AB  - We report the synthesis, incorporation into oligonucleotides, and base-pairing
      properties of the 2-thio-variant of iso-guanine. Iso-guanine is the purine
      component of a nonstandard base pair with 5-methyl-iso-cytosine. The 2-thio-iso
      guanine * 5-methyl-iso-cytosine base pair is found to have similar stability to
      an adenine * thymine pair.

PMID- 25965332
TI  - CuSO4/KI As Catalyst for the Synthesis of 1,4-Disubstituted-1,2,3-Triazolo
      Nucleosides.
AB  - A simple and inexpensive procedure has been developed for the selective formation
      of 1,4-disubstituted-1,2,3-triazolo-nucleosides starting from organic azides and
      terminal alkynes, mediated by in situ generated copper(I) catalyst from readily
      available CuSO4 and KI. 

PMID- 25965333
TI  - Lesch-Nyhan Syndrome in a Family with a Deletion Followed by an Insertion within
      the HPRT1 Gene.
AB  - Lesch-Nyhan syndrome (LNS) is a rare X-linked inherited neurogenetic disorder of
      purine metabolism in which the enzyme, hypoxanthine-guanine
      phosphoribosyltransferase(HGprt) is defective. The authors report a novel
      mutation which led to LNS in a family with a deletion followed by an insertion
      (INDELS) via the serial replication slippage mechanism:
      c.428_432delTGCAGinsAGCAAA, p.Met143Lysfs*12 in exon 6 of HPRT1 gene. Molecular
      diagnosis discloses the genetic heterogeneity of HPRT1 gene responsible for HGprt
      deficiency. It allows fast, accurate carrier detection and genetic counseling. 

PMID- 25965335
TI  - Bat Species Comparisons Based on External Morphology: A Test of Traditional
      versus Geometric Morphometric Approaches.
AB  - External morphology is commonly used to identify bats as well as to investigate
      flight and foraging behavior, typically relying on simple length and area
      measures or ratios. However, geometric morphometrics is increasingly used in the
      biological sciences to analyse variation in shape and discriminate among species
      and populations. Here we compare the ability of traditional versus geometric
      morphometric methods in discriminating between closely related bat species--in
      this case European horseshoe bats (Rhinolophidae, Chiroptera)--based on
      morphology of the wing, body and tail. In addition to comparing morphometric
      methods, we used geometric morphometrics to detect interspecies differences as
      shape changes. Geometric morphometrics yielded improved species discrimination
      relative to traditional methods. The predicted shape for the variation along the
      between group principal components revealed that the largest differences between
      species lay in the extent to which the wing reaches in the direction of the head.
      This strong trend in interspecific shape variation is associated with size, which
      we interpret as an evolutionary allometry pattern.

PMID- 25965334
TI  - A ribonucleoprotein complex protects the interleukin-6 mRNA from degradation by
      distinct herpesviral endonucleases.
AB  - During lytic Kaposi's sarcoma-associated herpesvirus (KSHV) infection, the viral
      endonuclease SOX promotes widespread degradation of cytoplasmic messenger RNA
      (mRNA). However, select mRNAs escape SOX-induced cleavage and remain robustly
      expressed. Prominent among these is interleukin-6 (IL-6), a growth factor
      important for survival of KSHV infected B cells. IL-6 escape is notable because
      it contains a sequence within its 3' untranslated region (UTR) that can confer
      protection when transferred to a SOX-targeted mRNA, and thus overrides the
      endonuclease targeting mechanism. Here, we pursued how this protective RNA
      element functions to maintain mRNA stability. Using affinity purification and
      mass spectrometry, we identified a set of proteins that associate specifically
      with the protective element. Although multiple proteins contributed to the escape
      mechanism, depletion of nucleolin (NCL) most severely impacted protection. NCL
      was re-localized out of the nucleolus during lytic KSHV infection, and its
      presence in the cytoplasm was required for protection. After loading onto the IL
      6 3' UTR, NCL differentially bound to the translation initiation factor eIF4H.
      Disrupting this interaction, or depleting eIF4H, reinstated SOX targeting of the
      RNA, suggesting that interactions between proteins bound to distant regions of
      the mRNA are important for escape. Finally, we found that the IL-6 3' UTR was
      also protected against mRNA degradation by the vhs endonuclease encoded by herpes
      simplex virus, despite the fact that its mechanism of mRNA targeting is distinct
      from SOX. These findings highlight how a multitude of RNA-protein interactions
      can impact endonuclease targeting, and identify new features underlying the
      regulation of the IL-6 mRNA. 

PMID- 25965336
TI  - The brain response to peripheral insulin declines with age: a contribution of the
      blood-brain barrier?
AB  - OBJECTIVES: It is a matter of debate whether impaired insulin action originates
      from a defect at the neural level or impaired transport of the hormone into the
      brain. In this study, we aimed to investigate the effect of aging on insulin
      concentrations in the periphery and the central nervous system as well as its
      impact on insulin-dependent brain activity. METHODS: Insulin, glucose and albumin
      concentrations were determined in 160 paired human serum and cerebrospinal fluid
      (CSF) samples. Additionally, insulin was applied in young and aged mice by
      subcutaneous injection or intracerebroventricularly to circumvent the blood-brain
      barrier. Insulin action and cortical activity were assessed by Western blotting
      and electrocorticography radiotelemetric measurements. RESULTS: In humans, CSF
      glucose and insulin concentrations were tightly correlated with the respective
      serum/plasma concentrations. The CSF/serum ratio for insulin was reduced in older
      subjects while the CSF/serum ratio for albumin increased with age like for most
      other proteins. Western blot analysis in murine whole brain lysates revealed
      impaired phosphorylation of AKT (P-AKT) in aged mice following peripheral insulin
      stimulation whereas P-AKT was comparable to levels in young mice after
      intracerebroventricular insulin application. As readout for insulin action in the
      brain, insulin-mediated cortical brain activity instantly increased in young mice
      subcutaneously injected with insulin but was significantly reduced and delayed in
      aged mice during the treatment period. When insulin was applied
      intracerebroventricularly into aged animals, brain activity was readily improved.
      CONCLUSIONS: This study discloses age-dependent changes in insulin CSF/serum
      ratios in humans. In the elderly, cerebral insulin resistance might be partially
      attributed to an impaired transport of insulin into the central nervous system.

PMID- 25965337
TI  - Independent data validation of an in vitro method for the prediction of the
      relative bioavailability of arsenic in contaminated soils.
AB  - In vitro bioaccessibility (IVBA) assays estimate arsenic (As) relative
      bioavailability (RBA) in contaminated soils to improve accuracy in human exposure
      assessments. Previous studies correlating soil As IVBA with RBA have been limited
      by the use of few soil types and sources of As, and the predictive value of As
      IVBA has not been validated using an independent set of As-contaminated soils. In
      this study, a robust linear model was developed to predict As RBA in mice using
      IVBA, and the predictive capability of the model was independently validated
      using a unique set of As-contaminated soils. Forty As-contaminated soils varying
      in soil type and contaminant source were included in this study, with 31 soils
      used for initial model development and nine soils used for independent model
      validation. The initial model reliably predicted As RBA values in the independent
      data set, with a mean As RBA prediction error of 5.4%. Following validation, 40
      soils were used for final model development, resulting in a linear model with the
      equation RBA = 0.65 * IVBA + 7.8 and an R(2) of 0.81. The in vivo-in vitro
      correlation and independent data validation presented provide critical
      verification necessary for regulatory acceptance in human health risk assessment.

PMID- 25965338
TI  - Journey of poly-nucleotides through OmpF porin.
AB  - OmpF is an abundant porin in many bacteria which attracts attention as a
      promising biological nanopore for DNA sequencing. We study the interactions of
      OmpF with pentameric poly-nucleotides (poly-Ns) in silico. The poly-N molecule is
      forced to translocate through the lumen of OmpF. Subsequently, the structural and
      dynamical effects of translocation steps on protein and poly-N molecules are
      explored in detail. The external loops of OmpF are introduced as the main region
      for discrimination of poly-Ns based on their organic bases. Structural network
      analyses of OmpF in the presence or absence of poly-Ns characterize special
      residues in the structural network of porin. These residues pave the way for
      engineering OmpF protein. The poly-N-specific pattern of OmpF's local conductance
      is detected in the current study. Computing the potential of mean force for
      translocation steps, we define the energetic barrier ahead of poly-N to move
      through OmpF's lumen. We suggest that fast translocation of the examined poly-N
      molecules through OmpF seems unattainable by small external driving forces. Our
      computational results suggest some abilities for OmpF porin like OmpF's potential
      for being used in poly-N sequencing. 

PMID- 25965339
TI  - Fluctuation mediated interactions due to rigidity mismatch and their effect on
      miscibility of lipid mixtures in multicomponent membranes.
AB  - We consider how membrane fluctuations can modify the miscibility of lipid
      mixtures, that is to say how the phase diagram of a boundary-constrained membrane
      is modified when the membrane is allowed to fluctuate freely in the case of zero
      surface tension. In order for fluctuations to have an effect, the different lipid
      types must have differing Gaussian rigidities. We show, somewhat paradoxically,
      that fluctuation-induced interactions can be treated approximately in a mean
      field type theory. Our calculations predict that, depending on the difference in
      bending and Gaussian rigidity of the lipids, membrane fluctuations can either
      favor or disfavor mixing. 

PMID- 25965340
TI  - Convex clustering: an attractive alternative to hierarchical clustering.
AB  - The primary goal in cluster analysis is to discover natural groupings of objects.
      The field of cluster analysis is crowded with diverse methods that make special
      assumptions about data and address different scientific aims. Despite its
      shortcomings in accuracy, hierarchical clustering is the dominant clustering
      method in bioinformatics. Biologists find the trees constructed by hierarchical
      clustering visually appealing and in tune with their evolutionary perspective.
      Hierarchical clustering operates on multiple scales simultaneously. This is
      essential, for instance, in transcriptome data, where one may be interested in
      making qualitative inferences about how lower-order relationships like gene
      modules lead to higher-order relationships like pathways or biological processes.
      The recently developed method of convex clustering preserves the visual appeal of
      hierarchical clustering while ameliorating its propensity to make false
      inferences in the presence of outliers and noise. The solution paths generated by
      convex clustering reveal relationships between clusters that are hidden by static
      methods such as k-means clustering. The current paper derives and tests a novel
      proximal distance algorithm for minimizing the objective function of convex
      clustering. The algorithm separates parameters, accommodates missing data, and
      supports prior information on relationships. Our program CONVEXCLUSTER
      incorporating the algorithm is implemented on ATI and nVidia graphics processing
      units (GPUs) for maximal speed. Several biological examples illustrate the
      strengths of convex clustering and the ability of the proximal distance algorithm
      to handle high-dimensional problems. CONVEXCLUSTER can be freely downloaded from
      the UCLA Human Genetics web site at http://www.genetics.ucla.edu/software/. 

PMID- 25965341
TI  - Treatment with Vitamin D/MOG Association Suppresses Experimental Autoimmune
      Encephalomyelitis.
AB  - Experimental autoimmune encephalomyelitis (EAE) is an animal model to study
      multiple sclerosis (MS). Considering the tolerogenic effects of active vitamin D,
      we evaluated the therapeutic effect of myelin oligodendrocyte glycoprotein (MOG)
      associated with active vitamin D in EAE development. EAE was induced in female
      C57BL/6 mice by immunization with MOG emulsified with Complete Freund's Adjuvant
      plus Mycobacterium tuberculosis. Animals also received two intraperitoneal doses
      of Bordetella pertussis toxin. One day after immunization, mice were treated with
      0,1 MUg of 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) every other day during 15
      days (on days 1, 3, 5, 7, 9, 11, 13 and 15). MOG (150 MUg) was co-administered on
      days 3 and 11. The administration of 1,25(OH)2D3 or MOG determined significant
      reduction in EAE incidence and in clinical scores. When MOG was associated with
      1,25(OH)2D3 the animals did not develop EAE. Spleen and central nervous system
      (CNS) cell cultures from this group produced less IL-6 and IL-17 upon stimulation
      with MOG in comparison to the EAE control group. In addition, this treatment
      inhibited dendritic cells maturation in the spleen and reduced inflammatory
      infiltration in the CNS. The association of MOG with 1,25(OH)2D3 was able to
      control EAE development.

PMID- 25965342
TI  - A Synthetic Lethal Screen Identifies DNA Repair Pathways that Sensitize Cancer
      Cells to Combined ATR Inhibition and Cisplatin Treatments.
AB  - The DNA damage response kinase ATR may be a useful cancer therapeutic target. ATR
      inhibition synergizes with loss of ERCC1, ATM, XRCC1 and DNA damaging
      chemotherapy agents. Clinical trials have begun using ATR inhibitors in
      combination with cisplatin. Here we report the first synthetic lethality screen
      with a combination treatment of an ATR inhibitor (ATRi) and cisplatin.
      Combination treatment with ATRi/cisplatin is synthetically lethal with loss of
      the TLS polymerase zeta and 53BP1. Other DNA repair pathways including homologous
      recombination and mismatch repair do not exhibit synthetic lethal interactions
      with ATRi/cisplatin, even though loss of some of these repair pathways sensitizes
      cells to cisplatin as a single-agent. We also report that ATRi strongly
      synergizes with PARP inhibition, even in homologous recombination-proficient
      backgrounds. Lastly, ATR inhibitors were able to resensitize cisplatin-resistant
      cell lines to cisplatin. These data provide a comprehensive analysis of DNA
      repair pathways that exhibit synthetic lethality with ATR inhibitors when
      combined with cisplatin chemotherapy, and will help guide patient selection
      strategies as ATR inhibitors progress into the cancer clinic. 

PMID- 25965343
TI  - Early oxygen-utilization and brain activity in preterm infants.
AB  - The combined monitoring of oxygen supply and delivery using Near-InfraRed
      spectroscopy (NIRS) and cerebral activity using amplitude-integrated EEG (aEEG)
      could yield new insights into brain metabolism and detect potentially vulnerable
      conditions soon after birth. The relationship between NIRS and quantitative
      aEEG/EEG parameters has not yet been investigated. Our aim was to study the
      association between oxygen utilization during the first 6 h after birth and
      simultaneously continuously monitored brain activity measured by aEEG/EEG. Forty
      four hemodynamically stable babies with a GA < 28 weeks, with good quality NIRS
      and aEEG/EEG data available and who did not receive morphine were included in the
      study. aEEG and NIRS monitoring started at NICU admission. The relation between
      regional cerebral oxygen saturation (rScO2) and cerebral fractional tissue oxygen
      extraction (cFTOE), and quantitative measurements of brain activity such as
      number of spontaneous activity transients (SAT) per minute (SAT rate), the
      interval in seconds (i.e. time) between SATs (ISI) and the minimum amplitude of
      the EEG in MUV (min aEEG) were evaluated. rScO2 was negatively associated with
      SAT rate (beta=-3.45 [CI=-5.76- -1.15], p=0.004) and positively associated with
      ISI (beta=1.45 [CI=0.44-2.45], p=0.006). cFTOE was positively associated with SAT
      rate (beta=0.034 [CI=0.009-0.059], p=0.008) and negatively associated with ISI
      (beta=-0.015 [CI=-0.026- -0.004], p=0.007). Oxygen delivery and utilization, as
      indicated by rScO2 and cFTOE, are directly related to functional brain activity,
      expressed by SAT rate and ISI during the first hours after birth, showing an
      increase in oxygen extraction in preterm infants with increased early electro
      cerebral activity. NIRS monitored oxygenation may be a useful biomarker of brain
      vulnerability in high-risk infants. 

PMID- 25965344
TI  - RNase HI Is Essential for Survival of Mycobacterium smegmatis.
AB  - RNases H are involved in the removal of RNA from RNA/DNA hybrids. Type I RNases H
      are thought to recognize and cleave the RNA/DNA duplex when at least four
      ribonucleotides are present. Here we investigated the importance of RNase H type
      I encoding genes for model organism Mycobacterium smegmatis. By performing gene
      replacement through homologous recombination, we demonstrate that each of the two
      presumable RNase H type I encoding genes, rnhA and MSMEG4305, can be removed from
      M. smegmatis genome without affecting the growth rate of the mutant. Further, we
      demonstrate that deletion of both RNases H type I encoding genes in M. smegmatis
      leads to synthetic lethality. Finally, we question the possibility of existence
      of RNase HI related alternative mode of initiation of DNA replication in M.
      smegmatis, the process initially discovered in Escherichia coli. We suspect that
      synthetic lethality of double mutant lacking RNases H type I is caused by
      formation of R-loops leading to collapse of replication forks. We report
      Mycobacterium smegmatis as the first bacterial species, where function of RNase H
      type I has been found essential. 

PMID- 25965345
TI  - Optimization of Invasion-Specific Effects of Betulin Derivatives on Prostate
      Cancer Cells through Lead Development.
AB  - The anti-invasive and anti-proliferative effects of betulins and abietane
      derivatives was systematically tested using an organotypic model system of
      advanced, castration-resistant prostate cancers. A preliminary screen of the
      initial set of 93 compounds was performed in two-dimensional (2D) growth
      conditions using non-transformed prostate epithelial cells (EP156T), an androgen
      sensitive prostate cancer cell line (LNCaP), and the castration-resistant, highly
      invasive cell line PC-3. The 25 most promising compounds were all betulin
      derivatives. These were selected for a focused secondary screen in three
      dimensional (3D) growth conditions, with the goal to identify the most effective
      and specific anti-invasive compounds. Additional sensitivity and cytotoxicity
      tests were then performed using an extended cell line panel. The effects of these
      compounds on cell cycle progression, mitosis, proliferation and unspecific
      cytotoxicity, versus their ability to specifically interfere with cell motility
      and tumor cell invasion was addressed. To identify potential mechanisms of action
      and likely compound targets, multiplex profiling of compound effects on a panel
      of 43 human protein kinases was performed. These target de-convolution studies,
      combined with the phenotypic analyses of multicellular organoids in 3D models,
      revealed specific inhibition of AKT signaling linked to effects on the
      organization of the actin cytoskeleton as the most likely driver of altered cell
      morphology and motility. 

PMID- 25965347
TI  - Fistulains A and B, New Bischromones from the Bark of Cassia fistula, and Their
      Activities.
AB  - Fistulains A and B (1 and 2), two novel bischromones with unique coupling
      patterns, alone with their biosynthetic related compound 3, were isolated from
      the bark of Cassia fistula. Fistulain A represents a new type of dimeric chromone
      alkaloid biogenetically derived from a chromone and a tricyclic alkaloid through
      an unusual C-14-N linkage. Fistulain B has a new carbon skeleton with a C-14-C-5'
      linkage formed between two different chromone units. Fistulain A displayed anti
      TMV activity, and both 1 and 2 showed weak cytotoxicities. 

PMID- 25965348
TI  - Carbon-11 radiolabelling of organosulfur compounds: (11) C synthesis of the
      progesterone receptor agonist tanaproget.
AB  - Herein a new (11) C radiolabelling strategy for the fast and efficient synthesis
      of thioureas and related derivatives using the novel synthon, (11) CS2 , is
      reported. This approach has enabled the facile labelling of a potent progesterone
      receptor (PR) agonist, [(11) C]Tanaproget, by the intramolecular reaction of the
      acyclic aminohydroxyl precursor with (11) CS2 , which has potential applications
      as a positron emission tomography radioligand for cancer imaging. 

PMID- 25965346
TI  - SP-R210 (Myo18A) Isoforms as Intrinsic Modulators of Macrophage Priming and
      Activation.
AB  - The surfactant protein (SP-A) receptor SP-R210 has been shown to increase
      phagocytosis of SP-A-bound pathogens and to modulate cytokine secretion by immune
      cells. SP-A plays an important role in pulmonary immunity by enhancing
      opsonization and clearance of pathogens and by modulating macrophage inflammatory
      responses. Alternative splicing of the Myo18A gene results in two isoforms: SP
      R210S and SP-R210L, with the latter predominantly expressed in alveolar
      macrophages. In this study we show that SP-A is required for optimal expression
      of SP-R210L on alveolar macrophages. Interestingly, pre-treatment with SP-A
      prepared by different methods either enhances or suppresses responsiveness to
      LPS, possibly due to differential co-isolation of SP-B or other proteins. We also
      report that dominant negative disruption of SP-R210L augments expression of
      receptors including SR-A, CD14, and CD36, and enhances macrophages' inflammatory
      response to TLR stimulation. Finally, because SP-A is known to modulate CD14, we
      used a variety of techniques to investigate how SP-R210 mediates the effect of SP
      A on CD14. These studies revealed a novel physical association between SP-R210S,
      CD14, and SR-A leading to an enhanced response to LPS, and found that SP-R210L
      and SP-R210S regulate internalization of CD14 via distinct macropinocytosis-like
      mechanisms. Together, our findings support a model in which SP-R210 isoforms
      differentially regulate trafficking, expression, and activation of innate immune
      receptors on macrophages. 

PMID- 25965350
TI  - Contact dermatitis: a practice parameter-update 2015.
AB  - This parameter was developed by the Joint Task Force on Practice Parameters,
      which represents the American Academy of Allergy, Asthma & Immunology (AAAAI);
      the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint
      Council of Allergy, Asthma & Immunology. The AAAAI and the ACAAI have jointly
      accepted responsibility for establishing "Contact Dermatitis: A Practice
      Parameter-Update 2015." This is a complete and comprehensive document at the
      current time. The medical environment is changing and not all recommendations
      will be appropriate or applicable to all patients. Because this document
      incorporated the efforts of many participants, no single individual, including
      members serving on the Joint Task Force, are authorized to provide an official
      AAAAI or ACAAI interpretation of these practice parameters. Any request for
      information or interpretation of this practice parameter by the AAAAI or ACAAI
      should be directed to the Executive Offices of the AAAAI, the ACAAI, and the
      Joint Council of Allergy, Asthma & Immunology. These parameters are not designed
      for use by the pharmaceutical industry in drug development or promotion.
      Previously published practice parameters of the Joint Task Force on Practice
      Parameters for Allergy & Immunology are available at http://www.JCAAI.org or
      http://www.allergyparameters.org.

PMID- 25965349
TI  - Prospective investigation of the impact of West Nile Virus infections in renal
      diseases.
AB  - An increased incidence of chronic kidney disease (CKD) after West Nile Virus
      (WNV) infections has been suggested but the association of WNV infections with
      renal damage remain inconclusive. This study was undertaken to characterize WNV
      infections in individuals with acute kidney injury (AKI) and CKD, and to evaluate
      hemodialysis as a probable transmission route. A total of 463 plasma and urine
      samples were collected from 45 AKI and 77 CKD patients. Nested and real-time
      polymerase chain reaction (PCR) assays were employed for viral RNA detection.
      Specific immunoglobulins were investigated via immunofluorescence and plaque
      reduction neutralization assays. Consecutive pre and post-dialysis samples were
      evaluated in CKD cases. WNV RNA and specific immunoglobulins were detected in 7
      (5.7%) and 5 (4.1%) individuals, respectively. The AKI patients with WNV RNA in
      blood and urine had underlying diseases requiring immunosuppressive therapy and
      demonstrated moderate to high viral loads. No clinical symptom related to WNV
      infection were observed in CKD cases with detectable viral nucleic acids. All WNV
      sequences were characterized as lineage 1 clade 1a and several amino acid
      substitutions with unknown impact were noted. Detailed epidemiologic
      investigation of WNV RNA positive CKD cases revealed probable vector-borne virus
      exposure, without the evidence for transmission via hemodialysis.

PMID- 25965351
TI  - Discovery and characterization of single nucleotide polymorphisms in coho salmon,
      Oncorhynchus kisutch.
AB  - Molecular population genetic analyses have become an integral part of ecological
      investigation and population monitoring for conservation and management.
      Microsatellites have been the molecular marker of choice for such applications
      over the last several decades, but single nucleotide polymorphism (SNP) markers
      are rapidly expanding beyond model organisms. Coho salmon (Oncorhynchus kisutch)
      is native to the north Pacific Ocean and its tributaries, where it is the focus
      of intensive fishery and conservation activities. As it is an anadromous species,
      coho salmon typically migrate across multiple jurisdictional boundaries,
      complicating management and requiring shared data collection methods. Here, we
      describe the discovery and validation of a suite of novel SNPs and associated
      genotyping assays which can be used in the genetic analyses of this species.
      These assays include 91 that are polymorphic in the species and one that
      discriminates it from a sister species, Chinook salmon. We demonstrate the
      utility of these SNPs for population assignment and phylogeographic analyses, and
      map them against the draft trout genome. The markers constitute a large majority
      of all SNP markers described for coho salmon and will enable both population- and
      pedigree-based analyses across the southern part of the species native range.

PMID- 25965352
TI  - Double-step CO2 sorption and guest-induced single-crystal-to-single-crystal
      transformation in a flexible porous framework.
AB  - A new 2D highly flexible and breathing porous framework [CuL(Me2NH)].DMF.H2O ()
      (H3L = 5-(4'-carboxylphenoxy)nicotinic acid) has been synthesized using a
      tritopic linker with a flexible joint. The desolvated framework, [CuL(Me2NH)] (),
      undergoes structural contraction, and exhibits selective and double-step
      hysteretic adsorption for CO2. Furthermore, on exposure to CH2Cl2 at room
      temperature, a unique single-crystal-to-single-crystal transformation occurred
      between and [Cu2L2(Me2NH)2(H2O)2].5H2O (). 

PMID- 25965353
TI  - Colorectal carcinoma: what should the oncologist recommend for screening?

PMID- 25965354
TI  - Immunologic checkpoints for cancer treatment: a continuing success.

PMID- 25965355
TI  - Immune checkpoint protein inhibition for cancer: preclinical justification for
      CTLA-4 and PD-1 blockade and new combinations.
AB  - Over the last two decades, our understanding of the molecular basis of immunity
      has revealed the complexity of regulatory pathways involved in immune responses
      to cancer. A significant body of data support the critical importance of immune
      checkpoints in the control of the adaptive immune response to malignancy, and
      suggest that inhibitors of those checkpoints might have significant utility in
      treating cancer. This has been borne out by the recent US Food and Drug
      Administration (FDA) approvals of two different antibodies, one against cytotoxic
      T-lymphocyte antigen-4 (CTLA-4) and one against programmed death-1 (PD-1). Here,
      we provide a comprehensive review of the literature regarding the preclinical
      justification for the use of CTLA-4 and PD-1 blockade as monotherapy, and as
      combination therapy in the treatment of cancer. The animal data strongly
      supported the use of these drugs in patients, and in many cases suggested
      strategies that directly led to successful registration trials. In contrast, many
      of the toxicities, and some of the unusual response patterns seen in patients
      with these drugs, were not predicted by the preclinical work that we cite,
      highlighting the importance of early-phase trials with patients to inform future
      drug development. In addition, we review herein the preclinical data surrounding
      emerging immune checkpoint proteins, including BTLA, VISTA, CD160, LAG3, TIM3,
      and CD244 as potential targets for inhibition. The current comprehensive review
      of the literature regarding CTLA-4 and PD-1, as well as a number of novel
      checkpoint proteins demonstrates a strong preclinical basis for the use of these
      antibodies singly and in combination to overcome checkpoint inhibition in the
      treatment of cancer. We also suggest that the use of these antibodies may augment
      the efficacy of other activating immune antibodies, cytokines, radiation, and
      adoptive cell therapy in human cancer.

PMID- 25965356
TI  - Immune response regulation in the tumor microenvironment by hypoxia.
AB  - Lymphocytes and myeloid cells sense hypoxia by the hypoxia-inducible factor (HIF)
      transcriptional system and via other molecular mechanisms. Low O2 availability is
      a hallmark of most solid tumors in which infiltrating leukocytes experience
      severe hypoxia once away from nurturing blood vessels. HIF controls migration,
      differentiation, and effector functions on immune cells. Importantly, in the
      tumor microenvironment the hypoxia response modulates the expression levels for
      important molecular targets in immunotherapy such as CD137, OX-40, FOXP3, and PD
      L1. Modulation by hypoxia of tumor-associated macrophages, myeloid-derived
      suppressor cells, and dendritic cells ought to play an important underexplored
      role in modulating tumor immunity. Overall, low O2 seems to invigorate some anti
      tumor effector T-cell functions while conflictingly favoring T-regulatory cells
      (Tregs) in terms of their differentiation, suppressive functions, and
      recruitment. Hypoxia also has been shown to uphold myeloid cell-mediated tumor
      promoting inflammation and the immunosuppressive functions of tumor-associated
      macrophages. Detailed research of this intricate and poorly understood balance is
      warranted to improve the outcome of cancer immunotherapy.

PMID- 25965357
TI  - The ipilimumab lesson in melanoma: achieving long-term survival.
AB  - The anti-cytotoxic T-lymphocyte antigen-4 (anti-CTLA-4) antibody ipilimumab is
      the first treatment that significantly improved the survival rates of metastatic
      melanoma patients, marking a new era in the treatment of melanoma. During its
      development, a hallmark of ipilimumab therapy was the extended duration of
      response, achieved in 20% of patients. The follow-up of patients included in
      phase II and phase III trials and in expanded access programs revealed that the
      survival rates remained stable after 3 years. These results demonstrated that
      ipilimumab induces an effective anti-tumor immune response persisting after the
      completion of treatment, and suggested a potential remission in a subset of
      patients. In this article we review the development of ipilimumab and highlight
      the long-term results. This approach emphasizes the need to optimize the use of
      ipilimumab in the future, by identifying the patients most likely to achieve long
      term survival after ipilimumab therapy, and by developing combined therapeutic
      approaches involving cytotoxic agents, targeted therapies or other
      immunotherapies to achieve durable control in a larger proportion of patients.

PMID- 25965358
TI  - Immunologic checkpoint blockade in lung cancer.
AB  - Despite the availability of radiotherapy, cytotoxic agents, and targeted agents,
      a high unmet medical need remains for novel therapies that improve treatment
      outcomes in patients with lung cancer who are ineligible for surgical resection.
      Building upon the early promise shown with general immunostimulatory agents,
      immuno-oncology is at the forefront of research in this field, with several novel
      agents currently under investigation. In particular, agents targeting immune
      checkpoints, such as the cytotoxic T-lymphocyte antigen-4 (CTLA-4) receptor and
      programmed death-1 (PD-1) receptor, have shown in early clinical trials potential
      for improving tumor responses and survival in patients with non-small cell lung
      cancer (NSCLC). Here, we examine the rationale for targeting immune checkpoints
      in lung cancer and review the clinical data from studies with immune checkpoint
      inhibitors currently in development. The challenges associated with optimizing
      treatment with these agents in lung cancer also are discussed.

PMID- 25965359
TI  - Immune checkpoint blockade in malignant mesothelioma.
AB  - Malignant mesothelioma (MM) is a highly aggressive malignancy with a very dismal
      prognosis. Current treatment for unresectable MM is largely unsatisfactory;
      therefore, new therapeutic approaches are eagerly awaited. A better understanding
      of the complex mechanisms of immune escape operated by neoplastic cells and the
      ability to unleash an efficient anti-tumor immune response by targeting
      regulatory immune checkpoint(s) with immunomodulatory monoclonal antibodies
      (mAbs), is leading to very promising clinical results in different tumor types.
      Herein, we highlight the clinical impact so far identified for these new
      immunomodulatory agents in MM patients and discuss their prospective use to
      design novel clinical trials.

PMID- 25965360
TI  - Toxicity patterns with immunomodulating antibodies and their combinations.
AB  - Immune checkpoint molecules cytotoxic T-lymphocyte antigen-4 (CTLA-4) and
      programmed death-1 (PD-1), but also LAG-3 and TIM-3, are involved in regulation
      of peripheral tolerance in order to prevent autoimmunity. Blocking of these cell
      surface proteins by antibodies has resulted in remarkable anti-tumor immunity;
      however this immunity is accompanied by immune-related adverse reactions (irAEs),
      resembling autoimmune diseases. Hence, treatment with immunosuppressive drugs is
      highly effective and resolves the symptoms caused by these adverse events
      rapidly. In this review, toxicity patterns observed with immune checkpoint
      blockade are described for single-agent and combination treatments.

PMID- 25965361
TI  - Immune checkpoint inhibitors in melanoma provide the cornerstones for curative
      therapies.
AB  - Immunotherapy has been revolutionalized by the concept of breaking tolerance. It
      represents a major paradigm shift that marks the beginning of a new era. The
      impact of the first checkpoint inhibitors, ie, anti-CTLA-4 (cytotoxic T
      lymphocyte antigen-4) and anti-PD-1/ anti-PD-L1 (programmed death-1 receptor and
      its ligand, PD-L1) is unprecedented. In only 5 years advanced melanoma has been
      transformed from an incurable disease into a curable disease, and we are only at
      the beginning of discovering its transversal impact throughout solid tumor
      oncology. In advanced melanoma response rates are about 12% for anti-CTLA-4 and
      about 40% for anti-PD-1, and are remarkably durable, hence their impact on
      survival. In melanoma anti-CTLA-4 (ipilimumab) was approved in 2011 and anti-PD-1
      (pembrolimumab) in 2014. Another anti-PD-1 antibody (nivolumab) has been recently
      approved based on phase III trial results in metastatic melanoma without BRAF
      mutation. Ipilimumab already has been evaluated in the adjuvant setting (European
      Organization for Research and Treatment of Cancer [EORTC] 18071) and shown to
      significantly improve recurrence-free survival in stage III patients at high risk
      of relapse. An adjuvant trial to evaluate pembrolizumab in this population (EORTC
      1325) was started in early 2015.

PMID- 25965363
TI  - Immunologic correlates in the course of treatment with immunomodulating
      antibodies.
AB  - Monoclonal antibodies (Ab) targeting immune checkpoints like CTLA-4 or PD-1 have
      come of age in the treatment of metastatic melanoma and further approvals are
      expected for other malignancies like lung and renal cell cancer as well. However,
      the majority of patients still do not experience clinical benefit upon these
      therapies. Moreover, immune-related side effects and the costs of these therapies
      prompt the search for their precise mode of action and for biomarker discovery.
      Here, we describe different classes of immunologic correlates such as
      pharmacodynamic changes observed in all treated patients, correlates with
      response during treatment (surrogate markers) or at the time-point of tumor
      assessment, as well as predictive markers for response and for immune-related
      adverse events. This review gives an overview of available data about correlates
      analyzed in the serum, all in immune cell subsets in the peripheral blood or in
      tumor-infiltrating lymphocytes. We will discuss how to prospectively validate and
      integrate these parameters for routine assessment of patients in daily clinical
      practice and give an outlook on promising future directions of biomarker
      research.

PMID- 25965362
TI  - Immune checkpoint blockade and interferon-alpha in melanoma.
AB  - The quality of the host immune response in patients with advanced melanoma is
      compromised with a bias towards Th2-type polarization and a tumor
      microenvironment that facilitates disease progression. Overcoming tumor-induced
      immune suppression through strategies that build upon the immunomodulatory
      qualities and clinical activity of interferon-alpha as demonstrated in the
      melanoma adjuvant setting is a major clinical need. The recent advances in the
      field of immune checkpoint modulation and the unprecedented clinical activity in
      advanced melanoma opens the door on novel combinations that may overcome tumor
      tolerogenic mechanisms that are known to suppress the potent anti-tumor impact of
      interferon (IFN)-alpha. Promising preliminary data suggest that such combinations
      may move the clinical management of advanced melanoma into the next level, beyond
      what is currently seen with immune checkpoint blockers alone.

PMID- 25965364
TI  - Immune checkpoint blockade in patients with melanoma metastatic to the brain.
AB  - Metastatic disease to the brain is a frequent manifestation of melanoma and is
      associated with a very poor outcome. Systemic therapy with cytotoxic chemotherapy
      provide only a minimal benefit, while surgery and radiotherapy provide in some
      patients local control but they less frequently affect the overall outcome of
      melanoma brain metastases (MBM). The advent of active systemic drugs has
      revolutioned the care of metastatic melanoma, but this benefit has not been
      translated into intracranial activity. However, since 2010 the anti-CTLA-4
      antibody ipilimumab and the BRAF inhibitors, dabrafenib and vemurafenib, have
      demonstrated initial signs of efficacy in active brain metastases. This chapter
      reviews the available data and rationale for ongoing and future trials of immune
      checkpoint-based combination therapy.

PMID- 25965365
TI  - Anti-PD-1 therapy in melanoma.
AB  - Immune-regulatory mechanisms are used by cancer to hide from the immune system.
      Advances and in-depth understanding of the biology of melanoma and its
      interaction with the immune system have led to the development of some of
      antagonistic antibodies to the programmed death 1 pathway (PD-1) and one of its
      ligands, programmed death ligand 1 (PD-L1), which are demonstrating high clinical
      benefit rates and tolerability. Blocking the immune-regulatory checkpoints that
      limit T-cell responses to melanoma upon PD-1/PD-L1 modulation has provided
      clinically validated targets for cancer immunotherapy. Combinations with other
      anti-melanoma agents may result in additional benefits. Nivolumab, pembrolizumab
      (formerly known as MK-3475 and lambrolizumab), and pidilizumab are anti-PD-1
      antibodies in clinical development for melanoma, non-small cell lung cancer,
      renal cell carcinoma, head and neck cancers, lymphoma, and several other cancers.
      Long-term survivors already have been reported with these therapies. In this
      review, we discuss the current state of anti-PD-1 agents, the evidence in the
      literature to support the combination of anti-PD-1 antibodies with other anti
      cancer agents and discuss the future directions for rational design of clinical
      trials that keep on increasing the number of long-term survivors.

PMID- 25965366
TI  - PD-L1 blockade for cancer treatment: MEDI4736.
AB  - MEDI4736 is a human immunoglobulin (Ig) G1k monoclonal antibody that blocks
      programmed cell death ligand-1 (PD-L1) binding to its receptors, allowing T cells
      to recognize and kill tumor cells. Key attributes include high affinity and
      selectivity for PD-L1, sustained drug exposure for up to 1 year of dosing, and
      engineering of the antibody to prevent antibody-dependent cell-mediated
      cytotoxicity. No immunogenicity impacting on the
      pharmacokinetics/pharmacodynamics of MEDI4736 has been reported at the 10 mg/kg
      every 2 weeks dose selected for further clinical development. The current safety
      profile and encouraging early anti-tumor activity of MEDI4736 support further
      clinical assessment. A broad development program for MEDI4736, both as
      monotherapy and in combination, is underway across a range of tumor types. This
      includes a large, multicenter, phase I, dose-escalation/expansion study in solid
      tumors (with a smaller corresponding study in Japanese patients), a phase I study
      in myelodysplastic syndrome, and a phase II study in advanced colorectal cancer.
      In addition, multiple phase I combination studies are ongoing with different
      agents, including those targeting MEK/BRAF in melanoma, epidermal growth factor
      receptor, programmed cell death-1, cytotoxic T-lymphocyte antigen-4, OX40,
      chemokine (C-C motif) receptor 4, and indoleamine 2,3-dioxygenase. Development is
      most advanced in non-small cell lung cancer, with a program currently comprising
      four pivotal studies and three phase I combination studies. A pivotal program for
      MEDI4736 in head and neck cancer began in late 2014.

PMID- 25965367
TI  - PD-L1 inhibition with MPDL3280A for solid tumors.
AB  - Cancer immunotherapy has become a popular anticancer approach, with the goal of
      stimulating immune responses against tumor cells. Recent evidence has
      demonstrated that the use of monoclonal antibodies targeting the programmed death
      ligand-1 (PD-L1)/programmed death-1 (PD-1) checkpoint pathway can result in well
      tolerated clinical responses in a wide variety of tumor types. This review
      summarizes the safety, clinical activity and biomarker data for the anti-PD-L1
      antibody, MPDL3280A, from a phase Ia multicenter, dose-escalation and -expansion
      trial. The data to date suggest that MPDL3280A is most effective in patients with
      pre-existing immunity suppressed by PD-L1 and reinvigorated upon antibody
      treatment.

PMID- 25965368
TI  - Therapeutic combinations of immune-modulating antibodies in melanoma and beyond.
AB  - Immune-modulating antibodies demonstrate activity in increasing numbers of
      malignancies, and more will be developed in the coming decade. Although active as
      single agents, optimal outcomes will require combination therapies for many
      patients. Currently, most combinations are based on either PD-1/PD-L1 antagonists
      or anti-CTLA-4. The combination of anti-PD-1 with anti-CTLA-4 demonstrates
      promising activity in metastatic melanoma and metastatic renal cell carcinoma and
      will be tested in multipe other malignancies. Future combinations will likely
      involve two or more checkpoint inhibitors, a checkpoint inhibitor in combination
      with an agonist of costimulation, combinations of costimulatory agents or
      combinations with antibodies that alter lymphyocyte trafficking. Although
      opportunities for effective combinations are available, major challeneges include
      the potential for autoimmune toxicity and the selection of patients.

PMID- 25965369
TI  - Immunologic checkpoints blockade in renal cell, prostate, and urothelial
      malignancies.
AB  - Genitourinary (GU) tumors, and in particular renal cell and prostate cancer,
      represent one of the most dynamic areas in oncology from the scientific point of
      view. One of the most recent treatment approaches for GU tumors has focused on a
      series of molecules known as immune checkpoints and the possibility of
      manipulating immune responses against tumor cells by blocking these molecules
      with monoclonal antibodies (mAbs). Cytotoxic T lymphocyte antigen-4 (CTLA-4), and
      the immune checkpoint inhibitor mAbs ipilimumab and tremelimumab, represent the
      prototypes of this new growing class of agents called immunomodulating
      antibodies, while programmed death/ligand 1 (PD-1/PD-L1) also has garnered a
      significant interest as a new immune checkpoints to target in urothelial cancer,
      with the anti-PD-1/PD-L1 inhibitor mAbs nivolumab, MPDL-3280, and BMS-936559 as
      the first agents tested. Here we report the encouraging initial data observed in
      GU cancers with this new class of agents, which have reinforced the interest of
      investigating the therapeutic potential of the immune checkpoint modulators in
      large controlled trials.

PMID- 25965370
TI  - Epigenetics meets immune checkpoints.
AB  - Epigenetic alterations play a pivotal role in cancer development and progression.
      Pharmacologic reversion of such alterations is feasible, and second generation
      "epigenetic drugs" are in development and have been demonstrated to possess
      significant immunomodulatory properties. This knowledge, together with the
      availability of new and highly effective immunotherapeutic agents including
      immune checkpoint(s) blocking monoclonal antibodies, allows us to plan for highly
      innovative proof-of-principle combination studies that will likely open the path
      to more effective anticancer therapies.

PMID- 25965371
TI  - Peri-operative management of heparin-induced thrombocytopenia syndrome in a
      patient with a suspected gynecologic malignancy.

PMID- 25965372
TI  - Advances in analytical methods and occurrence of organic UV-filters in the
      environment--A review.
AB  - UV-filters are a group of compounds designed mainly to protect skin against UVA
      and UVB radiation, but they are also included in plastics, furniture, etc., to
      protect products from light damage. Their massive use in sunscreens for skin
      protection has been increasing due to the awareness of the chronic and acute
      effects of UV radiation. Some organic UV-filters have raised significant concerns
      in the past few years for their continuous usage, persistent input and potential
      threat to ecological environment and human health. UV-filters end up in
      wastewater and because wastewater treatment plants are not efficient in removing
      them, lipophilic compounds tend to sorb onto sludge and hydrophilics end up in
      river water, contaminating the existing biota. To better understand the risk
      associated with UV-filters in the environment a thorough review regarding their
      physicochemical properties, toxicity and environmental degradation, analytical
      methods and their occurrence was conducted. Higher UV-filter concentrations were
      found in rivers, reaching 0.3mg/L for the most studied family, the benzophenone
      derivatives. Concentrations in the ng to MUg/L range were also detected for the p
      aminobenzoic acid, cinnamate, crylene and benzoyl methane derivatives in lake and
      sea water. Although at lower levels (few ng/L), UV-filters were also found in tap
      and groundwater. Swimming pool water is also a sink for UV-filters and its
      chlorine by-products, at the MUg/L range, highlighting the benzophenone and
      benzimidazole derivatives. Soils and sediments are not frequently studied, but
      concentrations in the MUg/L range have already been found especially for the
      benzophenone and crylene derivatives. Aquatic biota is frequently studied and UV
      filters are found in the ng/g-dw range with higher values for fish and mussels.
      It has been concluded that more information regarding UV-filter degradation
      studies both in water and sediments is necessary and environmental occurrences
      should be monitored more frequently and deeply.

PMID- 25965373
TI  - Polycyclic aromatic hydrocarbons in deep sea sediments: Microbe-pollutant
      interactions in a remote environment.
AB  - Recalcitrant polycyclic aromatic hydrocarbons (PAHs) released into seawater end
      up in the deep sea sediments (DSSs). However, their fate here is often
      oversimplified by theoretical models. Biodegradation of PAHs in DSSs, is assumed
      to be similar to biodegradation in surface habitats, despite high hydrostatic
      pressures and low temperatures that should significantly limit PAH
      biodegradation. Bacteria residing in the DSSs (related mainly to alpha- and gamma
      Proteobacteria) have been shown to or predicted to possess distinct genes,
      enzymes and metabolic pathways, indicating an adaptation of these bacterial
      communities to the psychro-peizophilic conditions of the DSSs. This work
      summarizes some of the most recent research on DSS hydrocarbonoclastic
      populations and mechanisms of PAH degradation and discusses the challenges posed
      by future high CO2 and UV climate scenarios on biodegradation of PAHs in DSSs. 

PMID- 25965374
TI  - [Not Available].

PMID- 25965375
TI  - Effects of asthma in nutritional status in children: A systematic review.
AB  - INTRODUCTION: Asthma is a chronic inflammatory disease of high prevalence,
      considered a public health problem and is thought to be one cause of low birth
      weight and growth retardation. PURPOSE: The purpose of this article was to review
      in literature the effects of asthma on the nutritional status in children.
      MATERIAL AND METHODS: A systematic review was made by searching for articles in
      PubMed, SciELO and LILACS databases. Review articles, studies with adults or
      research that did not evaluate the effects of asthma in children were excluded.
      Hence original articles in humans were included. RESULTS: In the systematic
      review we found 901 articles in MEDLINE (1966-1996), 47 in LILACS and SciELO in
      the 16 Brazil, totaling 964 articles. Of these, 17 articles were selected.
      CONCLUSION: Evidence that asthma interferes in nutritional status can not be
      proven in this study. Rev Port Pneumol 2010; XVI (4): 617-626.

PMID- 25965377
TI  - Optimal census by quorum sensing.
AB  - Quorum sensing is the regulation of gene expression in response to changes in
      cell density. To measure their cell density, bacterial populations produce and
      detect diffusible molecules called autoinducers. Individual bacteria internally
      represent the external concentration of autoinducers via the level of monitor
      proteins. In turn, these monitor proteins typically regulate both their own
      production and the production of autoinducers, thereby establishing internal and
      external feedbacks. Here, we ask whether feedbacks can increase the information
      available to cells about their local density. We quantify available information
      as the mutual information between the abundance of a monitor protein and the
      local cell density for biologically relevant models of quorum sensing. Using
      variational methods, we demonstrate that feedbacks can increase information
      transmission, allowing bacteria to resolve up to two additional ranges of cell
      density when compared with bistable quorum-sensing systems. Our analysis is
      relevant to multi-agent systems that track an external driver implicitly via an
      endogenously generated signal. 

PMID- 25965378
TI  - Effects of exercise during pregnancy on mode of delivery: a meta-analysis.
AB  - INTRODUCTION: We conducted a systematic review and meta-analysis to examine the
      influence of physical exercise interventions on the mode of delivery of healthy
      pregnant women with low to moderate levels of physical activity. MATERIAL AND
      METHODS: Key words were used to conduct a computerized search for articles on the
      topic in six databases: Cochrane Library Plus, Science Direct, EMBASE, PubMed,
      Web of Science and ClinicalTrials.gov. Ten randomized controlled trials were
      identified and included in the meta-analysis. Main outcome measures were mode of
      delivery (normal, instrumental vaginal, or cesarean delivery) and physical
      activity. RESULTS: Relative risk reductions and their 95% confidence interval
      were calculated for each study, and the heterogeneity of the studies was
      estimated using Cochran's Q statistic. The evidence suggests that physical
      exercise during pregnancy may increase the likelihood of normal delivery
      (relative risk = 1.12, 95% confidence interval 1.01-1.24; p = 0.041), in
      particular when exercise takes place during the second and third trimesters
      (relative risk = 1.14, 95% confidence interval 1.01-1.32; p = 0.048), even
      reducing the risk of cesarean delivery (relative risk = 0.66, 95% confidence
      interval 0.46-0.96; p = 0.028). CONCLUSIONS: Regular exercise during pregnancy
      appears to modestly increase the chance for normal delivery among healthy
      pregnant women. This applies to women with low to moderate levels of physical
      activity, but studies are needed to understand better the effect of physical
      exercise of moderate to vigorous intensity in the different trimesters.

PMID- 25965379
TI  - Effects of community-based natural resource management on household welfare in
      Namibia.
AB  - Biodiversity conservation, as an environmental goal, is increasingly recognized
      to be connected to the socioeconomic well-being of local communities. The
      development of a widespread community-based natural resource management (CBNRM)
      program in Namibia makes it an ideal location to analyze the connection between
      conservation and socioeconomic well-being of local communities. Namibia's CBNRM
      program involves the formation of communal conservancies within rural communities
      and previous studies have found it to be successful on both ecological and
      economic fronts. In order to broaden the understanding of the program's impact to
      include social factors, we have conducted a comparative analysis to determine the
      effects of this program on household welfare outcomes. Data from two rounds of
      the Namibia Demographic and Health Surveys (2000 and 2006/07) and quasi
      experimental statistical methods were used to evaluate changes in various health,
      education and wealth outcomes of those living in conservancies, relative to non
      conservancy comparison groups. Regression results indicate mixed effects of the
      conservancy program at the household level. The program had positive effects on
      some health outcome variables, including bednet ownership, which was twice as
      likely to increase over time in conservancy compared to non-conservancy
      households. Program impacts were negative for education outcomes, with the
      proportion of school attendance of conservancy children being 45% less likely to
      increase over time than non-conservancy children. Wealth outcome results were
      inconclusive. Our findings highlight the importance of analyzing community
      conservation programs at a variety of scales when evaluating overall impact, as
      community-level benefits may not necessarily extend down to the household level
      (and vice versa). 

PMID- 25965380
TI  - Nano-LC-MS/MS for Quantification of Lyso-Gb3 and Its Analogues Reveals a Useful
      Biomarker for Fabry Disease.
AB  - Biomarkers useful for diagnosis and evaluation of treatment for patients with
      Fabry disease are urgently needed. Recently, plasma globotriaosylsphingosine
      (lyso-Gb3) and lyso-Gb3-related analogues have attracted attention as promising
      biomarkers of Fabry disease. However, the plasma concentrations of lyso-Gb3 and
      its analogues are extremely low or below the detection limits in some Fabry
      patients as well as in healthy subjects. In this paper, we introduce the novel
      application of a nano-liquid chromatography-tandem mass spectrometry (nano-LC
      MS/MS) system to the measurement of lyso-Gb3 and its analogues in plasma. Nano-LC
      MS/MS requires smaller amounts of samples and is more sensitive than conventional
      techniques. Using this method, we measured the plasma concentrations of lyso-Gb3
      and its analogues in 40 healthy subjects, 5 functional variants (males with
      E66Q), and various Fabry patients (9 classic Fabry males/9 mutations; 7 later
      onset Fabry males/5 mutations; and 10 Fabry females/9 mutations). The results
      revealed that the mean lyso-Gb3 and lyso-Gb3(-2) concentrations in all the Fabry
      patient subgroups were statistically higher, especially in the classic Fabry
      males, than those in the functional variants and healthy subjects. The plasma
      concentrations of lyso-Gb3 and its analogues in healthy subjects, functional
      variants, and some Fabry patients with specific mutations (R112H and M296I) that
      cannot be established by conventional techniques were successfully determined by
      means of nano-LC-MS/MS. The lyso-Gb3 and lyso-Gb3(-2) concentrations in male
      patients with these mutations were lower than those in most Fabry patients having
      other mutations, but higher than those in the functional variants and healthy
      subjects. This new method is expected to be useful for sensitive determination of
      the plasma concentrations of lyso-Gb3 and its analogues. This study also revealed
      that not only lyso-Gb3 but also lyso-Gb3(-2) in plasma is a useful biomarker for
      the diagnosis of Fabry disease. 

PMID- 25965381
TI  - The MazEF Toxin-Antitoxin System Alters the beta-Lactam Susceptibility of
      Staphylococcus aureus.
AB  - Toxin-antitoxin (TA) systems are genetic elements of prokaryotes which encode a
      stable toxin and an unstable antitoxin that can counteract toxicity. TA systems
      residing on plasmids are often involved in episomal maintenance whereas those on
      chromosomes can have multiple functions. The opportunistic pathogen
      Staphylococcus aureus possesses at least four different families of TA systems
      but their physiological roles are elusive. The chromosomal mazEF system encodes
      the RNase toxin MazF and the antitoxin MazE. In the light of ambiguity regarding
      the cleavage activity, we here verify that MazF specifically targets UACAU
      sequences in S. aureus in vivo. In a native strain background and under non
      stress conditions, cleavage was observed in the absence or presence of mazE.
      Transcripts of spa (staphylococcal protein A) and rsbW (anti-sigmaB factor) were
      cut, but translational reporter fusions indicated that protein levels of the
      encoded products were unaffected. Despite a comparable growth rate as the wild
      type, an S. aureus mazEF deletion mutant was more susceptible to beta-lactam
      antibiotics, which suggests that further genes, putatively involved in the
      antibiotic stress response or cell wall synthesis or turnover, are controlled by
      this TA system. 

PMID- 25965382
TI  - Perceived morbidity, healthcare-seeking behavior and their determinants in a poor
      resource setting: observation from India.
AB  - BACKGROUND: To control the double burden of communicable and non-communicable
      diseases (NCDs), in the developing world, understanding the patterns of morbidity
      and healthcare-seeking is critical. The objective of this cross-sectional study
      was to determine the distribution, predictors and inter-relationship of perceived
      morbidity and related healthcare-seeking behavior in a poor-resource setting.
      METHODS: Between October 2013 and July 2014, 43999 consenting subjects were
      recruited from 10107 households in Malda district of West Bengal state in India,
      through multistage random sampling, using probability proportional-to-size.
      Information on socio-demographics, behaviors, recent ailments, perceived severity
      and healthcare-seeking were analyzed in SAS-9.3.2. RESULTS: Recent illnesses were
      reported by 55.91% (n=24,600) participants. Among diagnosed ailments (n=23,626),
      50.92% (n=12,031) were NCDs. Respiratory (17.28%, n=7605)), gastrointestinal
      (13.48%, n=5929) and musculoskeletal (6.25%, n=2749) problems were predominant.
      Non-qualified practitioners treated 53.16% (n=13,074) episodes. Older
      children/adolescents [adjusted odds ratio for private healthcare providers
      (AORPri)=0.76, 95% confidence interval=0.71-0.83) and for Govt. healthcare
      provider (AORGovt)=0.80(0.68-0.95)], females [AORGovt=0.80(0.73-0.88)], Muslims
      [AORPri=0.85(0.69-0.76) and AORGovt=0.92(0.87-0.96)], backward castes
      [AORGovt=0.93(0.91-0.96)] and rural residents [AORPri=0.82(0.75-0.89) and
      AORGovt=0.72(0.64-0.81)] had lower odds of visiting qualified practitioners.
      Apparently less severe NCDs [acid-peptic disorders: AORPri=0.41(0.37-0.46) &
      AORGovt=0.41(0.37-0.46), osteoarthritis: AORPri=0.72(0.59-0.68) &
      AORGovt=0.58(0.43-0.78)], gastrointestinal [AORPri=0.28(0.24-0.33) &
      AORGovt=0.69(0.58-0.81)], respiratory [AORPri=0.35(0.32-0.39) & AORGovt=0.46(0.41
      0.52)] and skin infections [AORPri=0.65(0.55-0.77)] were also less often treated
      by qualified practitioners. Better education [AORPri=1.91(1.65-2.22) for
      >=graduation], sanitation [AORPri=1.58(1.42-1.75)] and access to safe water
      [AORPri=1.33(1.05-1.67)] were associated with healthcare-seeking from qualified
      private practitioners. Longstanding NCDs [chronic obstructive pulmonary diseases:
      AORPri=1.80(1.46-2.23), hypertension: AORPri=1.94(1.60-2.36), diabetes:
      AORPri=4.94(3.55-6.87)] and serious infections [typhoid: AORPri=2.86(2.04-4.03)]
      were also more commonly treated by qualified private practitioners. Potential
      limitations included temporal ambiguity, reverse causation, generalizability
      issues and misclassification. CONCLUSION: In this poor-resource setting with high
      morbidity, ailments and their perceived severity were important predictors for
      healthcare-seeking. Interventions to improve awareness and healthcare-seeking
      among under-privileged and vulnerable population with efforts to improve the
      knowledge and practice of non-qualified practitioners probably required urgently.

PMID- 25965384
TI  - Characterization of a Highly pH Stable Chi-Class Glutathione S-Transferase from
      Synechocystis PCC 6803.
AB  - Glutathione S-transferases (GSTs) are multifunctional enzymes present in
      virtually all organisms. Besides having an essential role in cellular
      detoxification, they also perform various other functions, including responses in
      stress conditions and signaling. GSTs are highly studied in plants and animals;
      however, the knowledge regarding GSTs in cyanobacteria seems rudimentary. In this
      study, we report the characterization of a highly pH stable GST from the model
      cyanobacterium--Synechocystis PCC 6803. The gene sll0067 was expressed in
      Escherichia coli (E. coli), and the protein was purified to homogeneity. The
      expressed protein exists as a homo-dimer, which is composed of about 20 kDa
      subunit. The results of the steady-state enzyme kinetics displayed protein's
      glutathione conjugation activity towards its class specific substrate-
      isothiocyanate, having the maximal activity with phenethyl isothiocyanate.
      Contrary to the poor catalytic activity and low specificity towards standard GST
      substrates such as 1-chloro-2,4-dinitrobenzene by bacterial GSTs, PmGST B1-1 from
      Proteus mirabilis, and E. coli GST, sll0067 has broad substrate degradation
      capability like most of the mammalian GST. Moreover, we have shown that
      cyanobacterial GST sll0067 is catalytically efficient compared to the best
      mammalian enzymes. The structural stability of GST was studied as a function of
      pH. The fluorescence and CD spectroscopy in combination with size exclusion
      chromatography showed a highly stable nature of the protein over a broad pH range
      from 2.0 to 11.0. To the best of our knowledge, this is the first GST with such a
      wide range of pH related structural stability. Furthermore, the presence of
      conserved Proline-53, structural motifs such as N-capping box and hydrophobic
      staple further aid in the stability and proper folding of cyanobacterial GST
      sll0067.

PMID- 25965385
TI  - Fate of Zinc Oxide Nanoparticles Coated onto Macronutrient Fertilizers in an
      Alkaline Calcareous Soil.
AB  - Zinc oxide (ZnO) nanoparticles may provide a more soluble and plant available
      source of Zn in Zn fertilizers due to their greater reactivity compared to
      equivalent micron- or millimetre-sized (bulk) particles. However, the effect of
      soil on solubility, spatial distribution and speciation of ZnO nanoparticles has
      not yet been investigated. In this study, we examined the diffusion and solid
      phase speciation of Zn in an alkaline calcareous soil following application of
      nanoparticulate and bulk ZnO coated fertilizer products (monoammonium phosphate
      (MAP) and urea) using laboratory-based x-ray techniques and synchrotron-based MU
      x-ray fluorescence (MU-XRF) mapping and absorption fine structure spectroscopy
      (MU-XAFS). Mapping of the soil-fertilizer reaction zones revealed that most of
      the applied Zn for all treatments remained on the coated fertilizer granule or
      close to the point of application after five weeks of incubation in soil. Zinc
      precipitated mainly as scholzite (CaZn2(PO4)2.2H2O) and zinc ammonium phosphate
      (Zn(NH4)PO4) species at the surface of MAP granules. These reactions reduced
      dissolution and diffusion of Zn from the MAP granules. Although Zn remained as
      zincite (ZnO) at the surface of urea granules, limited diffusion of Zn from ZnO
      coated urea granules was also observed for both bulk and nanoparticulate ZnO
      treatments. This might be due to either the high pH of urea granules, which
      reduced solubility of Zn, or aggregation (due to high ionic strength) of released
      ZnO nanoparticles around the granule/point of application. The relative
      proportion of Zn(OH)2 and ZnCO3 species increased for all Zn treatments with
      increasing distance from coated MAP and urea granules in the calcareous soil.
      When coated on macronutrient fertilizers, Zn from ZnO nanoparticles (without
      surface modifiers) was not more mobile or diffusible compared to bulk forms of
      ZnO. The results also suggest that risk associated with the presence of ZnO NPs
      in calcareous soils would be the same as bulk sources of ZnO. 

PMID- 25965386
TI  - Circulating MicroRNAs as Non-Invasive Biomarkers for Early Detection of Non-Small
      Cell Lung Cancer.
AB  - BACKGROUND: Detection of lung cancer at an early stage by sensitive screening
      tests could be an important strategy to improving prognosis. Our objective was to
      identify a panel of circulating microRNAs in plasma that will contribute to early
      detection of lung cancer. MATERIAL AND METHODS: Plasma samples from 100 early
      stage (I to IIIA) non-small-cell lung cancer (NSCLC) patients and 100 non-cancer
      controls were screened for 754 circulating microRNAs via qRT-PCR, using TaqMan
      MicroRNA Arrays. Logistic regression with a lasso penalty was used to select a
      panel of microRNAs that discriminate between cases and controls. Internal
      validation of model discrimination was conducted by calculating the bootstrap
      optimism-corrected AUC for the selected model. RESULTS: We identified a panel of
      24 microRNAs with optimum classification performance. The combination of these 24
      microRNAs alone could discriminate lung cancer cases from non-cancer controls
      with an AUC of 0.92 (95% CI: 0.87-0.95). This classification improved to an AUC
      of 0.94 (95% CI: 0.90-0.97) following addition of sex, age and smoking status to
      the model. Internal validation of the model suggests that the discriminatory
      power of the panel will be high when applied to independent samples with a
      corrected AUC of 0.78 for the 24-miRNA panel alone. CONCLUSION: Our 24-microRNA
      predictor improves lung cancer prediction beyond that of known risk factors.

PMID- 25965387
TI  - Association between Glucocorticoid-Induced Osteoporosis and Myasthenia Gravis: A
      Cross-Sectional Study.
AB  - PURPOSE: To investigate the association between glucocorticoid-induced
      osteoporosis and myasthenia gravis (MG) using a cross-sectional survey in Japan.
      METHODS: We studied 363 patients with MG (female 68%; mean age, 57 +/- 16 years)
      who were followed at six Japanese centers between April and July 2012. We
      evaluated the clinical information of MG and fractures, bone markers, and
      radiological assessment. Quality of life was measured using an MG-specific
      battery, MG-QOL15. RESULTS: Glucocorticoids were administered in 283 (78%) of 363
      MG patients. Eighteen (6%) of 283 MG patients treated with prednisolone had a
      history of osteoporotic fractures. The duration of glucocorticoid therapy, but
      not the dose of prednisolone, was associated with the osteoporotic fractures in
      MG patients. Bone mineral density was significantly decreased in the MG patients
      with fractures. The multivariate analyses showed that the total quantitative MG
      score was the only independent factor associated with osteoporotic fractures (OR
      = 1.30, 95% CI 1.02-1.67, p = 0.03). MG patients who had experienced fractures
      reported more severe difficulties in activities of daily living. CONCLUSION:
      Glucocorticoid-induced osteoporosis aggravates quality of life in patients with
      MG.

PMID- 25965388
TI  - Randomized controlled trial of a six-week spiritual reminiscence intervention on
      hope, life satisfaction, and spiritual well-being in elderly with mild and
      moderate dementia.
AB  - OBJECTIVE: Reminiscence therapy has been reported to improve the well-being in
      patients with dementia. However, few studies have examined the effects of
      spiritual reminiscence, which emphasizes on reconnecting and enhancing the
      meaning of one's own experience, on patients with dementia. Therefore, this study
      aimed to investigate the effects of spiritual reminiscence on hope, life
      satisfaction, and spiritual well-being in elderly Taiwanese with mild or moderate
      dementia. METHODS: A randomized controlled trial was conducted on 103 patients
      with mild or moderate dementia recruited from a medical center in central Taiwan.
      The patients were randomly assigned to either a 6-week spiritual reminiscence
      group (n = 53) or control group (n = 50). The Herth Hope Index, the Life
      Satisfaction Scale, the Spirituality Index of Well-Being were administered before
      and after the 6-week period. RESULTS: The interaction terms between group and
      time for the three outcome measures were found to be significant (P < 0.001),
      indicating that the changes over time in them were different between the
      intervention and control groups. CONCLUSIONS: Findings of this randomized
      controlled trial showed that hope, life satisfaction, and spiritual well-being of
      elderly patients with mild or moderate dementia could significantly be improved
      with a 6-week spiritual reminiscence intervention.

PMID- 25965389
TI  - Simultaneous statistical inference for epigenetic data.
AB  - Epigenetic research leads to complex data structures. Since parametric model
      assumptions for the distribution of epigenetic data are hard to verify we
      introduce in the present work a nonparametric statistical framework for two-group
      comparisons. Furthermore, epigenetic analyses are often performed at various
      genetic loci simultaneously. Hence, in order to be able to draw valid conclusions
      for specific loci, an appropriate multiple testing correction is necessary.
      Finally, with technologies available for the simultaneous assessment of many
      interrelated biological parameters (such as gene arrays), statistical approaches
      also need to deal with a possibly unknown dependency structure in the data. Our
      statistical approach to the nonparametric comparison of two samples with
      independent multivariate observables is based on recently developed multivariate
      multiple permutation tests. We adapt their theory in order to cope with families
      of hypotheses regarding relative effects. Our results indicate that the
      multivariate multiple permutation test keeps the pre-assigned type I error level
      for the global null hypothesis. In combination with the closure principle, the
      family-wise error rate for the simultaneous test of the corresponding
      locus/parameter-specific null hypotheses can be controlled. In applications we
      demonstrate that group differences in epigenetic data can be detected reliably
      with our methodology. 

PMID- 25965390
TI  - Activation of AMPKalpha2 Is Not Required for Mitochondrial FAT/CD36 Accumulation
      during Exercise.
AB  - Exercise has been shown to induce the translocation of fatty acid translocase
      (FAT/CD36), a fatty acid transport protein, to both plasma and mitochondrial
      membranes. While previous studies have examined signals involved in the induction
      of FAT/CD36 translocation to sarcolemmal membranes, to date the signaling events
      responsible for FAT/CD36 accumulation on mitochondrial membranes have not been
      investigated. In the current study muscle contraction rapidly increased FAT/CD36
      on plasma membranes (7.5 minutes), while in contrast, FAT/CD36 only increased on
      mitochondrial membranes after 22.5 minutes of muscle contraction, a response that
      was exercise-intensity dependent. Considering that previous research has shown
      that AMP activated protein kinase (AMPK) alpha2 is not required for FAT/CD36
      translocation to the plasma membrane, we investigated whether AMPK alpha2
      signaling is necessary for mitochondrial FAT/CD36 accumulation. Administration of
      5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) induced AMPK
      phosphorylation, and resulted in FAT/CD36 accumulation on SS mitochondria,
      suggesting AMPK signaling may mediate this response. However, SS mitochondrial
      FAT/CD36 increased following acute treadmill running in both wild-type (WT) and
      AMPKalpha 2 kinase dead (KD) mice. These data suggest that AMPK signaling is not
      required for SS mitochondrial FAT/CD36 accumulation. The current data also
      implicates alternative signaling pathways that are exercise-intensity dependent,
      as IMF mitochondrial FAT/CD36 content only occurred at a higher power output.
      Taken altogether the current data suggests that activation of AMPK signaling is
      sufficient but not required for exercise-induced accumulation in mitochondrial
      FAT/CD36. 

PMID- 25965391
TI  - Pharmacological characterization of an antisense knockdown zebrafish model of
      Dravet syndrome: inhibition of epileptic seizures by the serotonin agonist
      fenfluramine.
AB  - Dravet syndrome (DS) is one of the most pharmacoresistant and devastating forms
      of childhood epilepsy syndromes. Distinct de novo mutations in the SCN1A gene are
      responsible for over 80% of DS cases. While DS is largely resistant to treatment
      with existing anti-epileptic drugs, promising results have been obtained in
      clinical trials with human patients treated with the serotonin agonist
      fenfluramine as an add-on therapeutic. We developed a zebrafish model of DS using
      morpholino antisense oligomers (MOs) targeting scn1Lab, the zebrafish ortholog of
      SCN1A. Zebrafish larvae with an antisense knockdown of scn1Lab (scn1Lab
      morphants) were characterized by automated behavioral tracking and high
      resolution video imaging, in addition to measuring brain activity through local
      field potential recordings. Our findings reveal that scn1Lab morphants display
      hyperactivity, convulsive seizure-like behavior, loss of posture, repetitive
      jerking and a myoclonic seizure-like pattern. The occurrence of spontaneous
      seizures was confirmed by local field potential recordings of the forebrain,
      measuring epileptiform discharges. Furthermore, we show that these larvae are
      remarkably sensitive to hyperthermia, similar to what has been described for
      mouse models of DS, as well as for human DS patients. Pharmacological evaluation
      revealed that sodium valproate and fenfluramine significantly reduce epileptiform
      discharges in scn1Lab morphants. Our findings for this zebrafish model of DS are
      in accordance with clinical data for human DS patients. To our knowledge, this is
      the first study demonstrating effective seizure inhibition of fenfluramine in an
      animal model of Dravet syndrome. Moreover, these results provide a basis for
      identifying novel analogs with improved activity and significantly milder or no
      side effects. 

PMID- 25965392
TI  - Ectopic expression of miR-494 inhibited the proliferation, invasion and
      chemoresistance of pancreatic cancer by regulating SIRT1 and c-Myc.
AB  - Recent researches demonstrate that microRNAs (miRNAs) are deregulated in numerous
      cancers and involved in tumorigenesis, whereas their influences on pancreatic
      cancer (PC) still need further elucidation. The present research revealed that
      miR-494 was significantly decreased in PC cell lines and tissues. Functional
      study showed that overexpressed miR-494 could remarkably inhibit proliferation of
      PC cells both in vitro and in vivo, which was due to induction of apoptosis, G1
      phase arrest and senescence. Moreover, upregulated miR-494 significantly
      prohibited invasion of PC cells. Meanwhile, both c-Myc and SIRT1 was identified
      as targets of miR-494 through dual luciferase assay and further confirmed by the
      reverse correlation between miR-494 and c-Myc/SIRT1 in PC samples. Furthermore,
      co-transfection with c-Myc-RNAi and SIRT1-RNAi synergistically reduced c-Myc and
      SIRT1 expression, and inhibited proliferation of PC, which simulated the effects
      of miR-494 overexpression. On the contrary, co-overexpression of c-Myc and SIRT1
      effectively rescued inhibition of overexpressed miR-494 on PC cells. The clinical
      characteristics further revealed that low miR-494 correlated with larger tumor
      size, late tumor node metastasis stage, lymphatic invasion, distant metastasis
      and poor prognosis. In conclusion, the present study indicated that miR-494 might
      serve as predictor and inhibitor in PC by directy downregulating the loop of c
      Myc and SIRT1. 

PMID- 25965394
TI  - AAV8(Y733F)-mediated gene therapy in a Spata7 knockout mouse model of Leber
      congenital amaurosis and retinitis pigmentosa.
AB  - Loss of SPATA7 function causes the pathogenesis of Leber congenital amaurosis and
      retinitis pigmentosa. Spata7 knockout mice mimic human SPATA7-related retinal
      disease with apparent photoreceptor degeneration observed as early as postnatal
      day 15 (P15). To test the efficacy of adeno-associated virus (AAV)-mediated gene
      therapy for rescue of photoreceptor survival and function in Spata7 mutant mice,
      we employed the AAV8(Y733F) vector carrying hGRK1-driven full-length FLAG-tagged
      Spata7 cDNA to target both rod and cone photoreceptors. Following subretinal
      injection of this vector, FLAG-tagged SPATA7 was found to colocalize with
      endogenous SPATA7 in wild-type mice. In Spata7 mutant mice initially treated at
      P15, we observed improvement of photoresponse, photoreceptor ultrastructure and
      significant alleviation of photoreceptor degeneration. Furthermore, we performed
      treatments at P28 and P56 and found that all treatments (P15-P56) can ameliorate
      rod and cone loss in the long term (1 year); however, none efficiently protect
      photoreceptors from degeneration by 86 weeks of age as only a small amount of
      treated photoreceptors can survive to this time. This study demonstrates long
      term improvement of photoreceptor function by AAV8(Y733F)-introduced Spata7
      expression in a mouse model as potential treatment of the human disease, but also
      suggests that treated mutant photoreceptors still undergo progressive
      degeneration. 

PMID- 25965393
TI  - Lentivirus-induced 'Smart' dendritic cells: Pharmacodynamics and GMP-compliant
      production for immunotherapy against TRP2-positive melanoma.
AB  - Monocyte-derived conventional dendritic cells (ConvDCs) loaded with melanoma
      antigens showed modest responses in clinical trials. Efficacy studies were
      hampered by difficulties in ConvDC manufacturing and low potency. Overcoming
      these issues, we demonstrated higher potency of lentiviral vector (LV)-programmed
      DCs. Monocytes were directly induced to self-differentiate into DCs (SmartDC
      TRP2) upon transduction with a tricistronic LV encoding for cytokines
      (granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL
      4)) and a melanoma antigen (tyrosinase-related protein 2 (TRP2)). Here, SmartDC
      TRP2 generated with monocytes from five advanced melanoma patients were tested in
      autologous DC:T cell stimulation assays, validating the activation of functional
      TRP2-specific cytotoxic T lymphocytes (CTLs) for all patients. We described
      methods compliant to good manufacturing practices (GMP) to produce LV and SmartDC
      TRP2. Feasibility of monocyte transduction in a bag system and cryopreservation
      following a 24-h standard operating procedure were achieved. After thawing, 50%
      of the initial monocyte input was recovered and SmartDC-TRP2 self-differentiated
      in vitro, showing uniform expression of DC markers, detectable LV copies and a
      polyclonal LV integration pattern not biased to oncogenic loci. GMP-grade SmartDC
      TRP2 expanded TRP2-specific autologous CTLs in vitro. These results demonstrated
      a simpler GMP-compliant method of manufacturing an effective individualized DC
      vaccine. Such DC vaccine, when in combination with checkpoint inhibition
      therapies, might provide higher specificity against melanoma. 

PMID- 25965395
TI  - Local administration of AAV-DJ pseudoserotype expressing COX2 provided early
      onset of transgene expression and promoted bone fracture healing in mice.
AB  - We have previously obtained compelling proof-of-principle evidence for COX2 gene
      therapy for fracture repair using integrating retroviral vectors. For this
      therapy to be suitable for patient uses, a suitable vector with high safety
      profile must be used. Accordingly, this study sought to evaluate the feasibility
      of AAV as the vector for this COX2 gene therapy, because AAV raises less safety
      issues than the retroviral vectors used previously. However, an appropriate AAV
      serotype is required to provide early increase in and adequate level of COX2
      expression that is needed for fracture repair. Herein, we reported that AAV-DJ,
      an artificial AAV pseudoserotype, is highly effective in delivering COX2 gene to
      fracture sites in a mouse femoral fracture model. Compared with AAV-2, the use of
      AAV-DJ led to ~5-fold increase in infectivity in mesenchymal stem cells (MSCs)
      and provided an earlier and significantly higher level of transgene expression at
      the fracture site. Injection of this vector at a dose of 7.5 * 10(11) genomic
      copies led to high COX2 level at the fracture site on day 3 after injections and
      significantly promoted fracture union at 21 days, as analyzed by radiography and
      MU-CT. The therapeutic effect appears to involve enhanced osteoblastic
      differentiation of MSCs and remodeling of callus tissues to laminar bone. This
      interpretation is supported by the enhanced expression of several key genes
      participating in the fracture repair process. In conclusion, AAV-DJ is a
      promising serotype for the AAV-based COX2 gene therapy of fracture repair in
      humans. 

PMID- 25965396
TI  - Neutralizing circulating ghrelin by expressing a growth hormone secretagogue
      receptor-based protein protects against high-fat diet-induced obesity in mice.
AB  - Ghrelin is a stomach-derived peptide hormone that stimulates appetite and
      promotes adiposity through binding to the growth hormone secretagogue receptor
      (GHS-R1a). Administration of ghrelin in rodents increases weight gain due to
      stimulating food intake and reducing fat utilization. Therefore, reducing
      circulating ghrelin levels holds the potential to reduce weight gain. We
      developed a GHS-R1a-fusion constructs of a decoy protein containing the ligand
      binding domains of the ghrelin receptor. Intramuscular injection of the GHSR/Fc
      plasmid decreased circulating levels of acylated-ghrelin. When challenged with
      the high fat diet, treated mice displayed reduced weight gain compared with
      controls, which was associated with reduced fat accumulation in the peritoneum
      but not lean mass. Quantitative PCR with reverse transcription showed increased
      PPARgamma and hormone sensitive lipase transcripts levels in adipose tissue of
      treated animals, illustrating a preference for increased fat utilization. Intra
      peritoneal glucose tolerance and insulin tolerance tests showed improved glucose
      clearance and insulin sensitivity in GHSR/Fc treated animals. We suggest that in
      vivo expression of the GHSR-based fusion protein prevents diet-induced weight
      gain, altering adipose gene expression and improving glucose tolerance. These
      findings, while confirming the role of ghrelin in peripheral energy metabolism,
      suggest that a strategy involving neutralization of the circulation ghrelin by
      intramuscular injection of the GHSR1/Fc fusion construct may find clinical
      application in the treatment of obesity. 

PMID- 25965397
TI  - Circulating Angiogenic Factors and the Risk of Adverse Outcomes among Haitian
      Women with Preeclampsia.
AB  - OBJECTIVE: Angiogenic factors are strongly associated with adverse maternal and
      fetal outcomes among women with preterm preeclampsia (PE) in developed countries.
      We evaluated the role of angiogenic factors and their relationship to adverse
      outcomes among Haitian women with PE. MATERIAL AND METHODS: We measured plasma
      antiangiogenic soluble fms-like tyrosine kinase 1 (sFlt1) and proangiogenic
      placental growth factor (PlGF) levels in women with PE (n=35) compared to
      controls with no hypertensive disorders (NHD) (n=43) among subjects with
      singleton pregnancies that delivered at Hospital Albert Schweitzer (HAS) in
      Haiti. We divided the preeclamptic women into two groups, early onset (<= 34
      weeks) and late onset (>34 weeks) and examined relationships between sFlt1/PlGF
      ratios on admission and adverse outcomes (abruption, respiratory complications,
      stroke, renal insufficiency, eclampsia, maternal death, birth weight <2500 grams,
      or fetal/neonatal death) in women with PE subgroups as compared to NHD groups
      separated by week of admission. Data are presented as median (25th-75th centile),
      n (%), and proportions. RESULTS: Among patients with PE, most (24/35) were
      admitted at term. Adverse outcome rates in PE were much higher among the early
      onset group compared to the late onset group (100.0% vs. 54.2%, P=0.007). Plasma
      angiogenic factors were dramatically altered in both subtypes of PE. Angiogenic
      factors also correlated with adverse outcomes in both subtypes of PE. The median
      sFlt1/PlGF ratios for subjects with early onset PE with any adverse outcome vs.
      NHD <=34 weeks with no adverse outcome were 703.1 (146.6, 1614.9) and 9.6 (3.5,
      58.6); P<0.001). Among late onset group the median sFlt1/PlGF ratio for women
      with any adverse outcome was 130.7 (56.1, 242.6) versus 22.4 (10.2, 58.7;
      P=0.005) in NHD >34 weeks with no adverse outcome. CONCLUSION: PE-related adverse
      outcomes are common in women in Haiti and are associated with profound angiogenic
      imbalance regardless of gestational age at presentation.

PMID- 25965398
TI  - Combining diffusion tensor imaging and gray matter volumetry to investigate motor
      functioning in chronic stroke.
AB  - Motor impairment after stroke is related to the integrity of the corticospinal
      tract (CST). However, considerable variability in motor impairment remains
      unexplained. To increase the accuracy in evaluating long-term motor function
      after ischemic stroke, we tested the hypothesis that combining diffusion tensor
      imaging (DTI) and gray matter (GM) volumetry can better characterize long-term
      motor deficit than either method alone in patients with chronic stroke. We
      recruited 31 patients whose Medical Research Council strength grade was <= 3/5 in
      the extensor muscles of the affected upper extremity in the acute phase. We used
      the Upper Extremity Fugl-Meyer (UE-FM) assessment to evaluate motor impairment,
      and as the primary outcome variable. We computed the fractional anisotropy ratio
      of the entire CST (CSTratio) and the volume of interest ratio (VOIratio), between
      ipsilesional and contralesional hemispheres, to explain long-term motor
      impairment. The results showed that CSTratio, VOIratio of motor-related brain
      regions, and VOIratio in the temporal lobe were correlated with UE-FM. A multiple
      regression model including CSTratio and VOIratio of the caudate nucleus explained
      40.7% of the variability in UE-FM. The adjusted R2 of the regression model with
      CSTratio as an independent variable was 29.4%, and that of using VOIratio of the
      caudate nucleus as an independent variable was 23.1%. These results suggest that
      combining DTI and GM volumetry may achieve better explanation of long-term motor
      deficit in stroke patients, than using either measure individually. This finding
      may provide guidance in determining optimal neurorehabilitative interventions. 

PMID- 25965399
TI  - Setting international standards for the management of public health pesticides.

PMID- 25965400
TI  - Casimir effects in systems containing 2D layers such as graphene and 2D electron
      gases.
AB  - We present a variety of methods to derive the Casimir interaction in planar
      systems containing 2D layers. Examples where this can be of use is graphene,
      graphene-like layers and 2D electron gases. We present results for two free
      standing layers and for one layer above a substrate. The results can easily be
      extended to systems with a larger number of layers. 

PMID- 25965402
TI  - Anatomical Considerations on the Alveolar Antral Artery as Related to the Sinus
      Augmentation Surgical Procedure.
AB  - BACKGROUND: The alveolar antral artery (AAA) is a vascular structure that often
      passes through the area of lateral window opening during sinus augmentation and
      can reach dimensions that, if the vessel is severed, can represent a serious
      complication of the surgical procedure. PURPOSE: With this narrative review, we
      aimed at summarizing the results obtained from all the studies that analyzed the
      variability in anatomical position and dimension of the AAA in order to give the
      clinician a reference when planning for a sinus augmentation surgery. MATERIALS
      AND METHODS: A search of available literature was conducted using electronic
      databases (PubMed and Medline) and manual searching. RESULTS: Detection rate of
      AAA on cone beam computerized tomography (CBCT) is variable and may depend upon
      the experience of the clinician. The course of the vessel is most frequently
      intraosseous, and its diameter, despite being smaller than 1 mm in most of the
      cases, can have a high incidence of diameters between 1 mm and 2 mm. Mean
      distances of the AAA from alveolar crest and sinus floor range from 11.25 mm to
      26.90 mm and 5.80 mm to 10.40 mm. CONCLUSIONS: Anatomical variants of the AAA
      that may increase the risk of severe intraoperatory bleeding are frequent and
      must be detected by the clinician implementing the use of the CBCT.

PMID- 25965401
TI  - In Vivo 7T MRI of the Non-Human Primate Brainstem.
AB  - Structural brain imaging provides a critical framework for performing
      stereotactic and intraoperative MRI-guided surgical procedures, with procedural
      efficacy often dependent upon visualization of the target with which to operate.
      Here, we describe tools for in vivo, subject-specific visualization and
      demarcation of regions within the brainstem. High-field 7T susceptibility
      weighted imaging and diffusion-weighted imaging of the brain were collected using
      a customized head coil from eight rhesus macaques. Fiber tracts including the
      superior cerebellar peduncle, medial lemniscus, and lateral lemniscus were
      identified using high-resolution probabilistic diffusion tractography, which
      resulted in three-dimensional fiber tract reconstructions that were comparable to
      those extracted from sequential application of a two-dimensional nonlinear brain
      atlas warping algorithm. In the susceptibility-weighted imaging, white matter
      tracts within the brainstem were also identified as hypointense regions, and the
      degree of hypointensity was age-dependent. This combination of imaging modalities
      also enabled identifying the location and extent of several brainstem nuclei,
      including the periaqueductal gray, pedunculopontine nucleus, and inferior
      colliculus. These clinically-relevant high-field imaging approaches have
      potential to enable more accurate and comprehensive subject-specific
      visualization of the brainstem and to ultimately improve patient-specific
      neurosurgical targeting procedures, including deep brain stimulation lead
      implantation. 

PMID- 25965403
TI  - Vitamin D deficiency--prognostic marker or mortality risk factor in end stage
      renal disease patients with diabetes mellitus treated with hemodialysis--a
      prospective multicenter study.
AB  - BACKGROUND: End stage renal disease (ESRD) patients on renal replacement therapy
      (RRT) with diabetes mellitus (DM) have a higher mortality rate and an increase
      prevalence of vitamin D deficiency compared to those without DM. It is still
      debated if vitamin D deficiency is a risk factor or a prognostic marker for
      mortality in these patients. This study investigated the prevalence of vitamin D
      deficiency and its impact on all-cause mortality in HD patients with DM. METHODS:
      Our prospective non-interventional cohort study included 600 patients on
      hemodialysis therapy (HD) (median aged 56, interquartile range (19) years, 332
      (55.3%) males) recruited from 7 HD centers, from all main geographical regions of
      Romania. The prevalence of DM was 15.3%. They were then followed regarding:
      dialysis duration, dialysis efficiency, renal anemia, CKD-MBD, inflammatory
      status and comorbidities: coronary artery disease (CAD), peripheral vascular
      disease (PVD) and stroke. The deficiency of 25-OH vitamin D was defined as a
      value lower than 12 ng/mL. RESULTS: Patients were followed for 3 years. The
      overall 3 year mortality was 25.5% (153 individuals), being higher in patients
      with DM as compared to those without DM (33.7% vs. 24.0%; P = 0.049). The time
      related prognosis was also influenced by the presence of DM, at the survival
      analysis resulting in a HR of 1.52 [1.03 to 2.26] 95% CI, P = 0.037, for death in
      dialyzed patients with DM. In DM patients, 25-OH vitamin D deficiency was
      significantly higher (37.0% compared to 24.0%, P = 0.009). Furthermore, in
      patients with DM we observed a shorter dialysis duration (2 vs. 3 years, P<0.001)
      and a lower intact parathyroid hormone (iPTH) (258.0 pg/ml vs. 441.9 pg/ml, P =
      0.002). Regarding the presence of comorbidities at the inclusion in the study,
      the presence of diabetes in dialyzed patients was associated with increased
      prevalence of CAD (87.0% vs. 58.1%, P<0.001), PVD (67.4% vs. 17.3%, P<0.001) and
      history of stroke (29.3% vs. 14.0%, P<0.001). In patients with DM the presence of
      25-OH vitamin D deficiency increased the probability of death (50.0% vs. 24.1%; P
      = 0.011). In multiple Cox proportional hazards analysis, vitamin D deficiency
      remained an independent predictor for mortality in dialysis patients with DM (HR
      = 1.71, 95% CI 1.21 to 2.43, P = 0.003). In the same time, multiple Cox
      proportional hazards analysis showed that age (HR = 1.02 per one year increase, P
      = 0.004), CAD (HR = 1.55, P = 0.046) and PVD (HR = 1.50, P = 0.029) were
      independent predictors for mortality in dialysis patients with DM. CONCLUSIONS:
      ESRD patients with DM treated with HD have a higher overall mortality than non-DM
      patients. Vitamin D deficiency is significantly more prevalent in HD patients
      with DM. Low 25-OH vitamin D levels were associated with increased all-cause
      mortality in these patients. According to our data, in HD patients with DM,
      screening for vitamin D deficiency (and its correction) should be mandatory for
      an optimal risk reduction strategy.

PMID- 25965405
TI  - Computational Design of Strain in Core-Shell Nanoparticles for Optimizing
      Catalytic Activity.
AB  - Surface strains in core-shell nanoparticles modify catalytic activity. Here, a
      continuum-based strategy enables accurate surface-strain-based screening and
      design of core-shell systems using minimal input as a means to enhance catalytic
      activity. The approach is validated here for Pt shells on Cu(x)Pt(1-x) cores and
      used to interpret experimental results on the oxygen reduction reaction in the
      same system. The analysis shows that precise control of particle sizes and shell
      thicknesses is required to achieve peak activity, rationalizing the limited
      increases in activity observed in experiments. The method is also applied to core
      shell nanorods to demonstrate its wide applicability.

PMID- 25965404
TI  - Influence of uncomplicated phacoemulsification on central macular thickness in
      diabetic patients: a meta-analysis.
AB  - OBJECTIVE: To evaluate the effect of uncomplicated phacoemulsification on central
      macular thickness (CMT) and best corrected visual acuity (BCVA) in both diabetic
      patients without diabetic retinopathy (DR) and diabetic patients with mild to
      moderate non-proliferative diabetic retinopathy (NPDR). METHODS: Potential
      prospective observational studies were searched through PubMed and EMBASE.
      Standardized mean difference (SMD) and 95% confidence interval (CI) for changes
      in CMT and BCVA were evaluated at postoperative 1, 3 and 6 months. The pooled
      effect estimates were calculated in the use of a random-effects model. RESULTS: A
      total of 10 studies involving 190 eyes of diabetic patients without diabetic
      retinopathy and 143 eyes of diabetic patients with NPDR were identified. CMT
      values demonstrated a statistically significant increase after uncomplicated
      phacoemulsification at 1 month (SMD, -0.814; 95%CI, -1.230 to -0.399), 3 months
      (SMD, -0.565; 95%CI, -0.927 to -0.202) and 6 months (SMD, -0.458; 95%CI, -0.739
      to -0.177) in diabetic patients with NPDR. There was no statistical difference in
      CMT values at postoperative 1 month (SMD, -1.206; 95%CI, -2.433 to 0.021)and no
      statistically significant increase in CMT values at postoperative3 months (SMD, 
      0.535; 95%CI, -1.252 to 0.182) and 6 months (SMD, -1.181; 95%CI, -2.625 to 0.263)
      in diabetic patients without DR.BCVA was significantly increased at postoperative
      1 month (SMD, 1.149; 95%CI, 0.251 to 2.047; and SMD,1.349; 95%CI, 0.264 to 2.434,
      respectively) and 6 months (SMD, 1.295; 95%CI, 0.494 to 2.096; and SMD, 2.146;
      95%CI, 0.172 to 4.120, respectively) in both diabetic patients without DR and
      diabetic patients with NPDR. Sensitivity analysis showed that the results were
      relatively stable and reliable. CONCLUSION: Uncomplicated phacoemulsification in
      diabetic patients with mild to moderate NPDR seemed to influence significantly
      the subclinical thickening of the macular zones at postoperative 1, 3 and 6
      months compared with diabetic patients without DR. BCVA was significantly
      improved in both diabetic patients without DR and diabetic patients with mild to
      moderate NPDR.

PMID- 25965406
TI  - Phase problem in the B-site ordering of La2CoMnO6: impact on structure and
      magnetism.
AB  - Epitaxial double perovskite La2CoMnO6 (LCMO) films were grown by metalorganic
      aerosol deposition on SrTiO3(111) substrates. A high Curie temperature, TC = 226
      K, and large magnetization close to saturation, MS(5 K) = 5.8MUB/f.u., indicate a
      97% degree of B-site (Co,Mn) ordering within the film. The Co/Mn ordering was
      directly imaged at the atomic scale by scanning transmission electron microscopy
      with energy-dispersive X-ray spectroscopy (STEM-EDX). Local electron-energy-loss
      spectroscopy (EELS) measurements reveal that the B-sites are predominantly
      occupied by Co(2+) and Mn(4+) ions in quantitative agreement with magnetic data.
      Relatively small values of the (1/2 1/2 1/2) superstructure peak intensity,
      obtained by X-ray diffraction (XRD), point out the existence of ordered domains
      with an arbitrary phase relationship across the domain boundary. The size of
      these domains is estimated to be in the range 35-170 nm according to TEM
      observations and modelling the magnetization data. These observations provide
      important information towards the complexity of the cation ordering phenomenon
      and its implications on magnetism in double perovskites, and similar materials. 

PMID- 25965407
TI  - The REporting of Studies Conducted Using Observational Routinely-Collected Health
      Data (RECORD) Statement: Methods for Arriving at Consensus and Developing
      Reporting Guidelines.
AB  - OBJECTIVE: Routinely collected health data, collected for administrative and
      clinical purposes, without specific a priori research questions, are increasingly
      used for observational, comparative effectiveness, health services research, and
      clinical trials. The rapid evolution and availability of routinely collected data
      for research has brought to light specific issues not addressed by existing
      reporting guidelines. The aim of the present project was to determine the
      priorities of stakeholders in order to guide the development of the REporting of
      studies Conducted using Observational Routinely-collected health Data (RECORD)
      statement. METHODS: Two modified electronic Delphi surveys were sent to
      stakeholders. The first determined themes deemed important to include in the
      RECORD statement, and was analyzed using qualitative methods. The second
      determined quantitative prioritization of the themes based on categorization of
      manuscript headings. The surveys were followed by a meeting of RECORD working
      committee, and re-engagement with stakeholders via an online commentary period.
      RESULTS: The qualitative survey (76 responses of 123 surveys sent) generated 10
      overarching themes and 13 themes derived from existing STROBE categories. Highest
      rated overall items for inclusion were: Disease/exposure identification
      algorithms; Characteristics of the population included in databases; and
      Characteristics of the data. In the quantitative survey (71 responses of 135
      sent), the importance assigned to each of the compiled themes varied depending on
      the manuscript section to which they were assigned. Following the working
      committee meeting, online ranking by stakeholders provided feedback and resulted
      in revision of the final checklist. CONCLUSIONS: The RECORD statement
      incorporated the suggestions provided by a large, diverse group of stakeholders
      to create a reporting checklist specific to observational research using
      routinely collected health data. Our findings point to unique aspects of studies
      conducted with routinely collected health data and the perceived need for better
      reporting of methodological issues.

PMID- 25965408
TI  - Structural basis for epitope masking and strain specificity of a conserved
      epitope in an intrinsically disordered malaria vaccine candidate.
AB  - Merozoite surface protein 2 (MSP2) is an intrinsically disordered, membrane
      anchored antigen of the malaria parasite Plasmodium falciparum. MSP2 can elicit a
      protective, albeit strain-specific, antibody response in humans. Antibodies are
      generated to the conserved N- and C-terminal regions but many of these react
      poorly with the native antigen on the parasite surface. Here we demonstrate that
      recognition of a conserved N-terminal epitope by mAb 6D8 is incompatible with the
      membrane-bound conformation of that region, suggesting a mechanism by which
      native MSP2 escapes antibody recognition. Furthermore, crystal structures and NMR
      spectroscopy identify transient, strain-specific interactions between the 6D8
      antibody and regions of MSP2 beyond the conserved epitope. These interactions
      account for the differential affinity of 6D8 for the two allelic families of
      MSP2, even though 6D8 binds to a fully conserved epitope. These results highlight
      unappreciated mechanisms that may modulate the specificity and efficacy of immune
      responses towards disordered antigens. 

PMID- 25965409
TI  - Titanium Elastic Nail (TEN) versus Reconstruction Plate Repair of Midshaft
      Clavicular Fractures: A Finite Element Study.
AB  - BACKGROUND: The biomechanical characteristics of midshaft clavicular fractures
      treated with titanium elastic nail (TEN) is unclear. This study aimed to present
      a biomechanical finite element analysis of biomechanical characteristics involved
      in TEN fixation and reconstruction plate fixation for midshaft clavicular
      fractures. METHODS: Finite element models of the intact clavicle and of midshaft
      clavicular fractures fixed with TEN and with a reconstruction plate were built.
      The distal clavicle displacement, peak stress, and stress distribution on the 3
      finite element models were calculated under the axial compression and cantilever
      bending. RESULTS: In both loading configurations, TEN generated the highest
      displacement of the distal clavicle, followed by the intact clavicle and the
      reconstruction plate. TEN showed higher peak bone and implant stresses, and is
      more likely to fail in both loading configurations compared with the
      reconstruction plate. TEN led to a stress distribution similar to that of the
      intact clavicle in both loading configurations, whereas the stress distribution
      with the reconstruction plate was nonphysiological in cantilever bending.
      CONCLUSIONS: TEN is generally preferable for treating simple displaced fractures
      of the midshaft clavicle, because it showed a stress distribution similar to the
      intact clavicle. However, TEN provides less stability, and excessive exercise of
      and weight bearing on the ipsilateral shoulder should be avoided in the early
      postoperative period. Fixation with a reconstruction plate was more stable but
      showed obvious stress shielding. Therefore, for patients with a demand for early
      return to activity, reconstruction plate fixation may be preferred.

PMID- 25965410
TI  - Transgenic Expression of Human CD46 on Porcine Endothelium: Effect on Coagulation
      and Fibrinolytic Cascades During Ex Vivo Human-to-Pig Limb Xenoperfusions.
AB  - BACKGROUND: Dysregulation of the coagulation system due to inflammatory responses
      and cross-species molecular incompatibilities represents a major obstacle to
      successful xenotransplantation. We hypothesized that complement inhibition
      mediated by transgenic expression of human CD46 in pigs might also regulate the
      coagulation and fibrinolysis cascades and tested this in ex vivo human-to-pig
      xenoperfusions. METHODS: Forelimbs of wild-type and hCD46/HLA-E double transgenic
      pigs were ex vivo xenoperfused for 12 hours with whole heparinized human blood.
      Muscle biopsies were stained for galactose-alpha1,3-galactose, immunoglobulin M,
      immunoglobulin G, complement, fibrin, tissue factor, fibrinogen-like protein 2,
      tissue plasminogen activator (tPA), and plasminogen activator inhibitor (PAI)-1.
      The PAI-1/tPA complexes, D-dimers, and prothrombin fragment F1 + 2 were measured
      in plasma samples after ex vivo xenoperfusion. RESULTS: No differences of
      galactose expression or deposition of immunoglobulin M and immunoglobulin G were
      found in xenoperfused tissues of wild type and transgenic limbs. In contrast,
      significantly lower deposition of C5b-9 (P < 0.0001), fibrin (P = 0.009), and
      diminished expression of tissue factor (P = 0.005) and fibrinogen-like protein 2
      (P = 0.028) were found in xenoperfused tissues of transgenic limbs. Levels of
      prothrombin fragment F1 + 2 (P = 0.031) and D-dimers (P = 0.044) were
      significantly lower in plasma samples obtained from transgenic as compared to
      wild-type pig limb perfusions. The expression of the fibrinolytic marker tPA was
      significantly higher (P = 0.009), whereas PAI-1 expression (P = 0.022) and PAI
      1/tPA complexes in plasma (P = 0.015) were lower after transgenic xenoperfusion
      as compared to wild-type xenoperfusions. CONCLUSIONS: In this human-to-pig
      xenoperfusion model, complement inhibition by transgenic hCD46 expression led to
      a significant inhibition of procoagulant and antifibrinolytic pathways.

PMID- 25965411
TI  - Development of a Minor Histocompatibility Antigen Vaccine Regimen in the Canine
      Model of Hematopoietic Cell Transplantation.
AB  - BACKGROUND: Minor histocompatibility antigen (miHA) vaccines have the potential
      to augment graft-versus-tumor effects without graft-versus-host disease (GVHD).
      We used mixed hematopoietic chimerism in the canine model of major
      histocompatibility complex-matched allogeneic hematopoietic cell transplantation
      as a platform to develop a miHA vaccination regimen. METHODS: We engineered DNA
      plasmids and replication-deficient human adenovirus type 5 constructs encoding
      large sections of canine SMCY and the entire canine SRY gene. RESULTS: Priming
      with replication-deficient human adenovirus type 5 constructs and boosting with
      ex vivo plasmid-transfected dendritic cells and cutaneous delivery of plasmids
      with a particle-mediated epidermal delivery device (PMED) in 2 female dogs
      induced antigen-specific T-cell responses. Similar responses were observed after
      a prime-boost vaccine regimen in three female hematopoietic cell transplantation
      donors. Subsequent donor lymphocyte infusion resulted in a significant change of
      chimerism in 1 of 3 male recipients without any signs of graft-versus-host
      disease. The change in chimerism in the recipient occurred in association with
      the development of CD4+ and CD8+ T-cell responses to the same peptide pools
      detected in the donor. CONCLUSIONS: These studies describe the first in vivo
      response to miHA vaccination in a large, outbred animal model without using
      recipient cells to sensitize the donor. This model provides a platform for
      ongoing experiments designed to define optimal miHA targets and develop protocols
      to directly vaccinate the recipient.

PMID- 25965412
TI  - Pleiotropic preconditioning-like cardioprotective effects of hypolipidemic drugs
      in acute ischemia-reperfusion in normal and hypertensive rats.
AB  - Although pleiotropy, which is defined as multiple effects derived from a single
      gene, was recognized many years ago, and considerable progress has since been
      achieved in this field, it is not very clear how much this feature of a drug is
      clinically relevant. During the last decade, beneficial pleiotropic effects from
      hypolipidemic drugs (as in, effects that are different from the primary ones)
      have been associated with reduction of cardiovascular risk. As with statins, the
      agonists of peroxisome proliferator-activated receptors (PPARs), niacin and
      fibrates, have been suggested to exhibit pleiotropic activity that could
      significantly modify the outcome of a cardiovascular ailment. This review
      examines findings demonstrating the impacts of treatment with hypolipidemic drugs
      on cardiac response to ischemia in a setting of acute ischemia-reperfusion, in
      relation to PPAR activation. Specifically, it addresses the issue of
      susceptibility to ischemia, with particular regard to the preconditioning-like
      cardioprotection conferred by hypolipidemic drugs, as well as the potential
      molecular mechanisms behind this cardioprotection. Finally, the involvement of
      PPAR activation in the mechanisms of non-metabolic cardioprotective effects from
      hypolipidemic drugs, and their effects on normal and pathologically altered
      myocardium (in the hearts of hypertensive rats) is also discussed. 

PMID- 25965413
TI  - Protonation and Proton-Coupled Electron Transfer at S-Ligated [4Fe-4S] Clusters.
AB  - Biological [Fe-S] clusters are increasingly recognized to undergo proton-coupled
      electron transfer (PCET), but the site of protonation, mechanism, and role for
      PCET remains largely unknown. Here we explore this reactivity with synthetic
      model clusters. Protonation of the arylthiolate-ligated [4Fe-4S] cluster [Fe4 S4
      (SAr)4 ](2-) (1, SAr=S-2,4-6-(iPr)3 C6 H2 ) leads to thiol dissociation,
      reversibly forming [Fe4 S4 (SAr)3 L](1-) (2) and ArSH (L=solvent, and/or
      conjugate base). Solutions of 2+ArSH react with the nitroxyl radical TEMPO to
      give [Fe4 S4 (SAr)4 ](1-) (1ox ) and TEMPOH. This reaction involves PCET coupled
      to thiolate association and may proceed via the unobserved protonated cluster
      [Fe4 S4 (SAr)3 (HSAr)](1-) (1-H). Similar reactions with this and related
      clusters proceed comparably. An understanding of the PCET thermochemistry of this
      cluster system has been developed, encompassing three different redox levels and
      two protonation states. 

PMID- 25965414
TI  - Antiparallel Self-Association of a gamma,alpha-Hybrid Peptide: More Relevance of
      Weak Interactions.
AB  - To learn how a preorganized peptide-based molecular template, together with
      diverse weak non-covalent interactions, leads to an effective self-association,
      we investigated the conformational characteristics of a simple gamma,alpha-hybrid
      model peptide, Boc-gamma-Abz-Gly-OMe. The single-crystal X-ray diffraction
      analysis revealed the existence of a fully extended beta-strand-like structure
      stabilized by two non-conventional C-H???O=C intramolecular H-bonds. The 2D (1) H
      NMR ROESY experiment led us to propose that the flat topology of the urethane
      gamma-Abz-amide moiety is predominantly preserved in a non-polar environment. The
      self-association of the energetically more favorable antiparallel beta-strand
      mimic in solid-state engenders an unusual 'flight of stairs' fabricated through
      face-to-face and edge-to-edge Ar???Ar interactions. In conjunction with FT-IR
      spectroscopic analysis in chloroform, we highlight that conformationally semi
      rigid gamma-Abz foldamer in appositely designed peptides may encourage unusual
      beta-strand or beta-sheet-like self-association and supramolecular organization
      stabilized via weak attractive forces. 

PMID- 25965415
TI  - 2D and 3D Anilato-Based Heterometallic M(I)M(III) Lattices: The Missing Link.
AB  - The similar bis-bidentate coordination mode of oxalato and anilato-based ligands
      is exploited here to create the first examples of 2D and 3D heterometallic
      lattices based on anilato ligands combining M(I) and a M(III) ions, phases
      already observed with oxalato but unknown with anilato-type ligands. These
      lattices are prepared with alkaline metal ions and magnetic chiral
      tris(anilato)metalate molecular building blocks: [M(III)(C6O4X2)3](3-) (M(III) =
      Fe and Cr; X = Cl and Br; (C6O4X2)(2-) = dianion of the 3,6-disubstituted
      derivatives of 2,5-dihydroxy-1,4-benzoquinone, H4C6O4). The new compounds include
      two very similar 2D lattices formulated as (PBu3Me)2[NaCr(C6O4Br2)3] (1) and
      (PPh3Et)2[KFe(C6O4Cl2)3](dmf)2 (2), both presenting hexagonal
      [M(I)M(III)(C6O4X2)3](2-) honeycomb layers with (PBu3Me)(+) in 1 or (PPh3Et)(+)
      and dmf in 2 inserted between them. Minor modifications in the synthetic
      conditions yield the novel 3D lattice (NEt3Me)[Na(dmf)][NaFe(C6O4Cl2)3] (3), in
      which hexagonal layers analogous to 1 and 2 are interconnected through Na(+)
      cations, and (NBu3Me)2[NaCr(C6O4Br2)3] (4), the first heterometallic 3D lattice
      based on anilato ligands. This compound presents two interlocked chiral 3D (10,3)
      lattices with opposite chiralities. Attempts to prepare 4 in larger quantities
      result in the 2D polymorph of compound 4 (4'). Magnetic properties of compounds
      1, 3, and 4' are reported, and in all cases we observe, as expected, paramagnetic
      behaviors that can be satisfactorily reproduced with simple monomer models
      including a zero field splitting (ZFS) of the corresponding S = 3/2 for Cr(III)
      in 1 and 4' or S = 5/2 for Fe(III) in 3. 

PMID- 25965416
TI  - Use of Fixed Dose Combination (FDC) Drugs in India: Central Regulatory Approval
      and Sales of FDCs Containing Non-Steroidal Anti-Inflammatory Drugs (NSAIDs),
      Metformin, or Psychotropic Drugs.
AB  - BACKGROUND: In 2012, an Indian parliamentary committee reported that
      manufacturing licenses for large numbers of fixed dose combination (FDC) drugs
      had been issued by state authorities without prior approval of the Central Drugs
      Standard Control Organization (CDSCO) in violation of rules, and considered that
      some ambiguity until 1 May 2002 about states' powers might have contributed. To
      our knowledge, no systematic enquiry has been undertaken to determine if evidence
      existed to support these findings. We investigated CDSCO approvals for and
      availability of oral FDC drugs in four therapeutic areas: analgesia (non
      steroidal anti-inflammatory drugs [NSAIDs]), diabetes (metformin),
      depression/anxiety (anti-depressants/benzodiazepines), and psychosis (anti
      psychotics). METHODS AND FINDINGS: This was an ecologic study with a time-trend
      analysis of FDC sales volumes (2007-2012) and a cross-sectional examination of
      2011-2012 data to establish the numbers of formulations on the market with and
      without a record of CDSCO approval ("approved" and "unapproved"), their branded
      products, and sales volumes. Data from the CDSCO on approved FDC formulations
      were compared with sales data from PharmaTrac, a database of national drug sales.
      We determined the proportions of FDC sales volumes (2011-2012) arising from
      centrally approved and unapproved formulations and from formulations including
      drugs banned/restricted internationally. We also determined the proportions of
      centrally approved and unapproved formulations marketed before and after 1 May
      2002, when amendments were made to the drug rules. FDC approvals in India, the
      United Kingdom (UK), and United States of America (US) were compared. For NSAID
      FDCs, 124 formulations were marketed, of which 34 (27%) were centrally approved
      and 90 (73%) were unapproved; metformin: 25 formulations, 20 (80%) approved, five
      (20%) unapproved; anti-depressants/benzodiazepines: 16 formulations, three (19%)
      approved, 13 (81%) unapproved; anti-psychotics: ten formulations, three (30%)
      approved, seven (70%) unapproved. After 1 May 2002, the proportions of approved
      FDC formulations increased for NSAIDs (26%/28%) and anti-psychotics (0%/38%) and
      decreased for metformin (100%/75%) and anti-depressants/benzodiazepines
      (20%/18%), and the overall proportion approved remained similar before and after
      that date. FDC formulations gave rise to multiple branded products, ranging from
      211 anti-psychotic FDC products from ten formulations to 2,739 NSAID FDC products
      from 124 formulations. The proportions of FDC sales volumes arising from
      unapproved formulations were as follows: anti-depressants/benzodiazepines, 69%;
      anti-psychotics, 43%; NSAIDs, 28%; and metformin, 0.4%. Formulations including
      drugs banned/restricted internationally comprised over 12% of NSAID FDC sales and
      53% of anti-psychotic FDC sales. Across the four therapeutic areas, 14 FDC
      formulations were approved in the UK and 22 in the US. CONCLUSIONS: There was
      evidence supporting concerns about FDCs. Metformin excepted, substantial numbers
      of centrally unapproved formulations for NSAID, anti-depressant/benzodiazepine,
      and anti-psychotic FDCs were marketed; sales volumes were high. The legal need
      for central approval of new drugs before manufacture has been in place
      continuously since 1961, including for FDCs meeting the applicable legal test.
      Proportions of centrally unapproved formulations after 1 May 2002 did not
      decrease overall, and no ambiguity was found about states' licensing powers.
      Unapproved formulations should be banned immediately, prioritising those
      withdrawn/banned internationally and undertaking a review of benefits and risks
      for patients in ceasing or switching to other medicines. Drug laws need to be
      amended to ensure the safety and effectiveness of medicines marketed in India.

PMID- 25965417
TI  - Effect of imidazolium-based ionic liquids on bacterial growth inhibition
      investigated via experimental and QSAR modelling studies.
AB  - Tuning the characteristics of solvents to fit industrial requirements has
      currently become a major interest in both academic and industrial communities,
      notably in the field of room temperature ionic liquids (RTILs), which are
      considered one of the most promising green alternatives to molecular organic
      solvents. In this work, several sets of imidazolium-based ionic liquids were
      synthesized, and their toxicities were assessed towards four human pathogens
      bacteria to investigate how tunability can affect this characteristic.
      Additionally, the toxicity of particular RTILs bearing an amino acid anion was
      introduced in this work. EC50 values (50% effective concentration) were
      established, and significant variations were observed; although all studied ILs
      displayed an imidazolium moiety, the toxicity values were found to vary between
      0.05 mM for the most toxic to 85.57 mM for the least toxic. Linear quantitative
      structure activity relationship models were then developed using the charge
      density distribution (sigma-profiles) as molecular descriptors, which can yield
      accuracies as high as 95%.

PMID- 25965418
TI  - A functional single-nucleotide polymorphism in the ERCC1 gene alters the efficacy
      of narrowband ultraviolet B therapy in patients with active vitiligo in a Chinese
      population.
AB  - BACKGROUND: T lymphocytes have been shown to cause the destruction of melanocytes
      in vitiligo pathogenesis. Narrowband ultraviolet B (NB-UVB), as an effective
      therapeutic strategy in vitiligo, can lead to the formation of DNA photoproducts
      such as cyclobutane pyrimidine dimers (CPDs) in perilesional lymphocytes and thus
      induce skin immunosuppression. The repair of DNA photoproducts is performed
      mainly through the nucleotide excision repair (NER) pathway. We hypothesized that
      single-nucleotide polymorphisms (SNPs) in NER genes might influence the repair
      capacity of CPDs and thus contribute to variations in phototherapy efficiency.
      OBJECTIVES: To detect genetic polymorphisms in NER genes and their relationship
      with the efficacy of NB-UVB therapy in patients with active vitiligo. METHODS: We
      investigated the association of NER SNPs (XPA A23G, XPC Ci11A, XPC C2919A and
      ERCC1 C118T) with phototherapy efficacy in 86 patients with vitiligo who received
      NB-UVB treatment. Furthermore, we examined the impact of ERCC1 C118T on the
      apoptosis of T lymphocytes and CPD accumulation after NB-UVB irradiation.
      RESULTS: We found that patients with vitiligo with the ERCC1 codon 118 CC
      genotype showed better efficacy after NB-UVB irradiation than those with the
      ERCC1 118 TT and CT genotypes, whereas no such association was documented among
      the genotypes of XPA A23G, XPC Ci11A or XPC C2919A. Additionally, the apoptosis
      rates and CPD levels of lymphocytes after NB-UVB irradiation in patients with the
      ERCC1 118 CC genotype were significantly higher than those in patients with the
      ERCC1 118 TT and CT genotypes. CONCLUSIONS: The ERCC1 118 CC genotype confers
      better efficacy of NB-UVB therapy in patients with active vitiligo.

PMID- 25965419
TI  - Screening-level estimates of mass discharge uncertainty from point measurement
      methods.
AB  - The uncertainty of mass discharge measurements associated with point-scale
      measurement techniques was investigated by deriving analytical solutions for the
      mass discharge coefficient of variation for two simplified, conceptual models. In
      the first case, a depth-averaged domain was assumed, consisting of one
      dimensional groundwater flow perpendicular to a one-dimensional control plane of
      uniformly spaced sampling points. The contaminant flux along the control plane
      was assumed to be normally distributed. The second case consisted of one
      dimensional groundwater flow perpendicular to a two-dimensional control plane of
      uniformly spaced sampling points. The contaminant flux in this case was assumed
      to be distributed according to a bivariate normal distribution. The center point
      for the flux distributions in both cases was allowed to vary in the domain of the
      control plane as a uniform random variable. Simplified equations for the
      uncertainty were investigated to facilitate screening-level evaluations of
      uncertainty as a function of sampling network design. Results were used to
      express uncertainty as a function of the length of the control plane and number
      of wells, or alternatively as a function of the sample spacing. Uncertainty was
      also expressed as a function of a new dimensionless parameter, Omega, defined as
      the ratio of the maximum local flux to the product of mass discharge and sample
      density. Expressing uncertainty as a function of Omega provided a convenient
      means to demonstrate the relationship between uncertainty, the magnitude of a
      local hot spot, magnitude of mass discharge, distribution of the contaminant
      across the control plane, and the sampling density. 

PMID- 25965420
TI  - Design and construction of an inexpensive homemade plant growth chamber.
AB  - Plant growth chambers produce controlled environments, which are crucial in
      making reproducible observations in experimental plant biology research.
      Commercial plant growth chambers can provide precise controls of environmental
      parameters, such as temperature, humidity, and light cycle, and the capability
      via complex programming to regulate these environmental parameters. But they are
      expensive. The high cost of maintaining a controlled growth environment is often
      a limiting factor when determining experiment size and feasibility. To overcome
      the limitation of commercial growth chambers, we designed and constructed an
      inexpensive plant growth chamber with consumer products for a material cost of
      $2,300. For a comparable growth space, a commercial plant growth chamber could
      cost $40,000 or more. Our plant growth chamber had outside dimensions of 1.5 m
      (W) x 1.8 m (D) x 2 m (H), providing a total growth area of 4.5 m2 with 40-cm
      high clearance. The dimensions of the growth area and height can be flexibly
      changed. Fluorescent lights with large reflectors provided a relatively spatially
      uniform photosynthetically active radiation intensity of 140-250 MUmoles/m2/sec.
      A portable air conditioner provided an ample cooling capacity, and a cooling
      water mister acted as a powerful humidifier. Temperature, relative humidity, and
      light cycle inside the chamber were controlled via a z-wave home automation
      system, which allowed the environmental parameters to be monitored and programmed
      through the internet. In our setting, the temperature was tightly controlled:
      22.2 degrees C+/-0.8 degrees C. The one-hour average relative humidity was
      maintained at 75%+/-7% with short spikes up to +/-15%. Using the interaction
      between Arabidopsis and one of its bacterial pathogens as a test experimental
      system, we demonstrate that experimental results produced in our chamber were
      highly comparable to those obtained in a commercial growth chamber. In summary,
      our design of an inexpensive plant growth chamber will tremendously increase
      research opportunities in experimental plant biology. 

PMID- 25965421
TI  - Peripapillary retinal nerve fiber layer changes in preclinical diabetic
      retinopathy: a meta-analysis.
AB  - BACKGROUND: Diabetic retinopathy is a microvascular neurodegenerative disorder in
      diabetic patients. Peripapillary retinal nerve fiber layer changes have been
      described in patients with preclinical diabetic retinopathy, but study results
      have been inconsistent. OBJECTIVE: To assess changes in peripapillary retinal
      nerve fiber layer thickness in diabetic patients with preclinical diabetic
      retinopathy. METHODS: A literature search was conducted through PubMed, EMBASE,
      Web of Science and Cochrane Library. Case-control studies on RNFL thickness in
      preclinical diabetic retinopathy patients and healthy controls were retrieved. A
      meta-analysis of weighted mean difference and a sensitivity analysis were
      performed using RevMan 5.2 software. RESULTS: Thirteen case-control studies
      containing 668 diabetic patients and 556 healthy controls were selected.
      Peripapillary RNFL thickness was significantly reduced in patients with
      preclinical diabetic retinopathy compared to healthy controls in studies applying
      Optical Coherence Tomography (-2.88 MUm, 95%CI: -4.44 to -1.32, P = 0.0003) and
      in studies applying Scanning Laser Polarimeter (-4.21 MUm, 95%CI: -6.45 to -1.97,
      P = 0.0002). Reduction of RNFL thickness was significant in the superior quadrant
      (-3.79 MUm, 95%CI: -7.08 to -0.50, P = 0.02), the inferior quadrant (-2.99 MUm,
      95%CI: -5.44 to -0.54, P = 0.02) and the nasal quadrant (-2.88 MUm, 95%CI: -4.93
      to -0.82, P = 0.006), but was not significant in the temporal quadrant (-1.22
      MUm, 95%CI: -3.21 to 0.76, P = 0.23), in diabetic patients. CONCLUSION:
      Peripapillary RNFL thickness was significantly decreased in preclinical diabetic
      retinopathy patients compared to healthy control. Neurodegenerative changes due
      to preclinical diabetic retinopathy need more attention.

PMID- 25965422
TI  - On the worrying fate of Data Deficient amphibians.
AB  - The 'Data Deficient' (DD) category of the IUCN Red List assembles species that
      cannot be placed in another category due to insufficient information. This
      process generates uncertainty about whether these species are safe or actually in
      danger. Here, we give a global overview on the current situation of DD amphibian
      species (almost a quarter of living amphibians) considering land-use change
      through habitat modification, the degree of protection of each species and the
      socio-political context of each country harboring DD species. We found that DD
      amphibians have, on average, 81% of their ranges totally outside protected areas.
      Worryingly, more than half of DD species have less than 1% of their distribution
      represented in protected areas. Furthermore, the percentage of overlap between
      species' range and human-modified landscapes is high, at approximately 58%. Many
      countries harboring a large number of DD species show a worrying socio-political
      trend illustrated by substantial, recent incremental increases in the Human
      Development Index and lower incremental increases in the establishment of
      protected areas. Most of these are African countries, which are located mainly in
      the central and southern regions of the continent. Other countries with similar
      socio-political trends are in southeastern Asia, Central America, and in the
      northern region of South America. This situation is concerning, but it also
      creates a huge opportunity for considering DD amphibians in future conservation
      assessments, planning, and policy at different levels of government
      administration. 

PMID- 25965423
TI  - Coronary artery fistula: a review.
AB  - Coronary arterial fistulas are abnormal connections between the coronary arteries
      and the chambers of the heart or major thoracic vessels. Although first described
      in 1841, the true incidence is difficult to evaluate because approximately half
      of the cases may be asymptomatic and clinically undetectable. This review will
      discuss the history and prevalence of coronary artery fistulas and their
      morphology, histology, presentation, diagnosis, treatment options, and
      complications.

PMID- 25965424
TI  - Activity of alpha-Aminoadipate Reductase Depends on the N-Terminally Extending
      Domain.
AB  - L-alpha-Aminoadipic acid reductases catalyze the ATP- and NADPH-dependent
      reduction of L-alpha-aminoadipic acid to the corresponding 6-semialdehyde during
      fungal L-lysine biosynthesis. These reductases resemble peptide synthetases with
      regard to their multidomain composition but feature a unique domain of elusive
      function--now referred to as an adenylation activating (ADA) domain--that extends
      the reductase N-terminally. Truncated enzymes based on NPS3, the L-alpha
      aminoadipic acid reductase of the basidiomycete Ceriporiopsis subvermispora,
      lacking the ADA domain either partially or entirely were tested for activity in
      vitro, together with an ADA-adenylation didomain and the ADA domainless
      adenylation domain. We provide evidence that the ADA domain is required for
      substrate adenylation: that is, the initial step of the catalytic turnover. Our
      biochemical data are supported by in silico modeling that identified the ADA
      domain as a partial peptide synthetase condensation domain.

PMID- 25965425
TI  - Catalytic Enantioselective Reaction of alpha-Phenylthioacetonitriles with Imines
      Using Chiral Bis(imidazoline)-Palladium Catalysts.
AB  - The catalytic enantioselective reaction of alpha-phenylthioacetonitriles with
      imines has been developed. The reaction of various imines proceeds in good yields
      and diastereo- and enantioselectivities in the presence of chiral
      bis(imidazoline)-palladium catalysts. The obtained products can be converted into
      beta-aminonitrile or beta-aminoamide compounds without loss of enantiopurity. 

PMID- 25965426
TI  - Halogenative difluorohomologation of ketones.
AB  - A method for the difluorohomologation of ketones accompanied by halogenation of a
      C-H bond is described. The reaction involves silylation, difluorocarbene addition
      using Me3SiCF2Br activated by a bromide ion, and halogenation of intermediate
      cyclopropanes with N-bromo- or N-iodosuccinimide. The whole process is performed
      without isolation of intermediates. The resulting alpha,alpha-difluoro-beta-halo
      substituted ketones can be readily converted into fluorine containing pyrazole
      derivatives and oxetanes. 

PMID- 25965427
TI  - Classical van der Waals heat flow between oscillators and between half-spaces.
AB  - We find the steady-state heat flow P between two classical harmonic oscillators
      having natural frequency omega0, dynamically identical, damped, and acted on by
      Langevin forces appropriate, respectively, to temperatures T1 and T2 (with
      k(B)T1,2 ? homega0). Retardation and relativistic effects are disregarded.
      Considered individually, each of the two normal modes of the joint system behaves
      as if it were in equilibrium at the average temperature (T1 + T2)/2, but the
      modes are correlated, and it is these correlations that govern P. From P one
      readily calculates the classical heat flow per unit area between two Drude
      modelled half-spaces. It emerges that, by contrast to equilibrium statistical
      mechanics, theories of such steady-state systems must generally specify the
      mechanism they envisage for enforcing the nominally prescribed temperatures.

PMID- 25965428
TI  - Glutathione replenishing potential of CeO2 nanoparticles in human breast and
      fibrosarcoma cells.
AB  - Recently, cerium oxide nanoparticles (CeO2 NPs) has been reported for multi
      enzyme mimetic activities like that of superoxide dismutase and catalase. Here,
      we report glutathione (GSH) replenishing response by CeO2 NPs in human breast
      (MCF-7) and fibrosarcoma (HT-1080) cells. CeO2 NPs were found to be mostly
      cuboidal in shape with average diameter of 25 nm. Effects on cell viability,
      reactive oxygen species (ROS) generation, and mitochondrial outer membrane
      potential (MOMP) suggested CeO2 NPs to be reasonably non-cytotoxic. Data on
      membrane damage and lipid peroxidation correlated well with the cell viability
      results suggesting NPs of CeO2 to be biocompatible. Interestingly, CeO2 NPs
      significantly increased intracellular GSH in cells challenged with oxidants.
      Replenishment of depleted GSH in oxidatively challenged cells was comparable with
      the GSH restoring potential of known antioxidant N-acetyl cysteine (NAC), a
      precursor of GSH. Like NAC, CeO2 NPs significantly replenished depleted GSH in
      both cell types challenged with hydrogen peroxide (H2O2) and zinc oxide (ZnO)
      NPs. Moreover, CeO2 NPs treated cells were significantly protected from
      cytotoxicity caused by H2O2 and ZnO NPs. Our findings, therefore, suggest CeO2
      NPs as a potential antioxidant rather than a toxic material.

PMID- 25965429
TI  - Graphene/nickel nanoparticles composites from graphenide solutions.
AB  - Nanocomposites between nickel nanoparticles and graphene were obtained starting
      from nickel cations and graphenide solutions (negatively charged graphene layers)
      as both reducing agent to nickel cations and graphene source. Different
      nanomaterials were obtained in two different solvents, N-methyl-2-pyrrolidone
      (NMP) and tetrahydrofuran (THF), with different nickel/graphene ratios. The
      nanomaterials were characterized by UV-Vis spectroscopy, transmission electron
      microscopy (TEM), scanning electron microscopy (SEM), thermogravimetric analysis
      (TGA), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS),
      energy dispersive X-ray spectroscopy (EDS), cyclic voltammetry (CV) and
      electrochemical impedance spectroscopy (EIS). All the samples consist of large
      graphene layers highly decorated with crystalline nickel nanoparticles, of size
      ranging from 2 to 10 nm. Thin films of the samples were deposited on indium-tin
      oxide (ITO) substrates and electrochemically characterized in alkaline medium,
      leading to Ni(OH)2/NiOOH redox pair, where the increase of the nickel proportion
      in the nanocomposites resulted in higher peak currents. The samples obtained in
      NMP showed the best performance with a fivefold increase of the peak currents,
      consistent with the lower charge transfer resistance as seen by electrochemical
      impedance spectroscopy (EIS).

PMID- 25965431
TI  - Superhydrophobic (low adhesion) and parahydrophobic (high adhesion) surfaces with
      micro/nanostructures or nanofilaments.
AB  - Controlling the water adhesion is extremely important for various applications
      such as for water harvesting. Here, superhydrophobic (low adhesion) and
      parahydrophobic (high adhesion) substrates are both obtained from hydrophilic
      polymers. We show in the work that a judicious choice in the monomer structure
      used for electropolymerization can lead to these two properties. Using a phenyl
      group, parahydrophobic properties are reached due to the formation of
      nanofilaments. By contrast, using a naphthalene or a biphenyl group,
      superhydrophobic properties are obtained due the formation of both micro- and
      nanostructures. 

PMID- 25965430
TI  - Preparation of Ag@Ag3PO4@ZnO ternary heterostructures for photocatalytic studies.
AB  - In this article, we report a novel Ag@Ag3PO4@ZnO ternary heterostructures
      synthesized through a three-step approach. Firstly, single-crystalline Ag
      nanorods are fabricated and served as the templates for subsequent Ag3PO4
      deposition. Secondly, Ag3PO4 crystals are grown around Ag core nanorods through a
      solution co-precipitation process, leading to the Ag@Ag3PO4 binary
      heterostructures. Finally, ZnO nanorod arrays on the surface of the Ag@Ag3PO4
      heterostructures are realized via a seeded growth strategy, forming the typical
      Ag@Ag3PO4@ZnO ternary heterostructures. The photodegradation of rhodamine B under
      ultraviolet-visible light irradiation indicates that the Ag@Ag3PO4@ZnO ternary
      heterostructures exhibit much higher activities than pure Ag3PO4 and binary
      heterostructures of Ag@Ag3PO4. The higher photocatalytic activity of the
      Ag@Ag3PO4@ZnO composites may be attributed to the effective photogenerated charge
      separation at heterointerfaces of Ag/Ag3PO4 and Ag3PO4/ZnO, and the rapid
      electron transport along one-dimensional Ag and ZnO nanorods. 

PMID- 25965432
TI  - Probing the potential of apigenin liposomes in enhancing bacterial membrane
      perturbation and integrity loss.
AB  - Along with discovery of new antibacterial agents, it is important to develop
      novel drug delivery systems to effectively deliver drugs within bacterial cells
      for enhanced therapeutic activity. Liposomes have been extensively investigated
      as pharmaceutical carriers for improvement of therapeutic index of antimicrobial
      agents. The aim of this present study was to evaluate the antibacterial activity
      of free and liposomal formulation of apigenin, a plant based isoflavone and
      elucidate the mode of action. Distearoylphosphatidylcholine liposomes were
      prepared having nano-range particle size (104.3+/-1.8 nm), narrow particle
      distribution (0.204) and high encapsulation efficiency of apigenin (89.9+/
      2.31%). Antibacterial activity of apigenin and efficacy of liposome-mediated
      apigenin delivery were determined from minimum inhibitory concentration values.
      Interaction studies using electron microscopy revealed adherence and fusion of
      liposomal apigenin with the bacteria causing membrane perturbation through
      reactive oxygen species generation which was evaluated by epi-fluorescence
      microscopy and fluorescence activated cell sorting. The interaction of apigenin
      liposomes with bacterial membrane increased intracellular drug concentration and
      thus, can be employed to deliver apigenin within cells to augment its
      antibacterial activity. Increased efficacy and hemocompatibility of this
      formulation paves way for future evaluation of underlying molecular mechanisms
      and in vivo testing for enhanced therapeutic effects.

PMID- 25965433
TI  - Synthesis of magnetron sputtered WO3 nanoparticles-degradation of 2-chloroethyl
      ethyl sulfide and dimethyl methyl phosphonate.
AB  - In the present study, tungsten oxide nanoparticles were synthesized using DC
      magnetron sputtering and investigated their potential for decontamination of 2
      chloroethyl ethyl sulfide (CEES) and dimethyl methyl phosphonate (DMMP). The
      tungsten oxide nanoparticles were characterized by Powder XRD, FE-SEM, EDS, TEM,
      TGA, N2-BET and FT-IR techniques. The XRD patterns of as-deposited and post
      annealed tungsten oxide nanoparticles reveal that the crystallite size of
      detected monoclinic phase WO3 nanoparticle was increased with increasing
      annealing temperatures. The phase and increase in particles size of WO3
      nanoparticles were also confirmed by Raman and TEM analyses. The obtained surface
      area (~63-33 m(2)/g) of magnetron sputtered WO3 nanoparticles was found to be
      enhanced significantly as compared to reported surface area of WO3 nanoparticles
      synthesis by various techniques. The study of degradation reactions of CEES and
      DMMP on the surface of obtained nanoparticles was carried out by using GC and GC
      MS techniques. The decontamination reactions were found to be pseudo first order
      steady state with rate constant (k) and half life values 0.143-0.109 h(-1) and
      4.82-6.49 h for CEES and 0.018-0.010 h(-1) and 36.87-66.65 h for DMMP,
      respectively. The FT-IR data reveal the role of hydrolysis reactions in the
      decontamination of CEES as well as DMMP.

PMID- 25965434
TI  - Intercalation and adsorption of ciprofloxacin by layered chalcogenides and
      kinetics study.
AB  - The hydrothermally synthesized layered chalcogenide, K(2x)Mn(x)Sn(3-x)S6 (x=0.5
      0.95) (KMS-1), was applied to remove ciprofloxacin from aqueous solution. Kinetic
      data showed the removal reaction followed a pseudo-second-order kinetic model and
      the rate controlling step was both through external film and intraparticle
      diffusion. The adsorption of CIP by KMS-1 is endothermic and the maximum
      adsorption capacity of KMS-1 was 199.6, 230.9 and 269.5 mg/g at temperature of
      10, 25 and 40 degrees C, respectively. The heavy metal ions had great effect on
      the removal efficiency of CIP and the degree of inhibition followed the order:
      Pb(2+)>Zn(2+)>Cd(2+)>Ni(2+). The shift of Bragg peaks from XRD at various pH
      accompanying CIP removal and FE-SEM images confirmed that cation exchange is the
      major mechanism for the adsorption of CIP by KMS-1. In the pH range of 4.0-7.0,
      the intercalation of cationic CIP adopted a titled orientation of di-molecular
      CIP in KMS-1 with the titling angle of 68 degrees  and 42 degrees , respectively.
      A vertical arrangement of the zwitterionic CIP adsorbed on the surface of KMS-1
      was also confirmed. These results suggested that KMS-1 is an effective adsorbent
      to remove CIP from water.

PMID- 25965436
TI  - Choledochoduodenostomy for biliary drainage of malignant obstruction after failed
      endoscopic retrograde cholangiopancreatography.

PMID- 25965437
TI  - Hepatocellular carcinoma: Consensus, controversies and future directions. A
      report from the Canadian Association for the Study of the Liver Hepatocellular
      Carcinoma Meeting.
AB  - Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality
      worldwide and its incidence has rapidly increased in North America in recent
      years. Although there are many published guidelines to assist the clinician,
      there remain gaps in knowledge and areas of controversy surrounding the diagnosis
      and management of HCC. In February 2014, the Canadian Association for the Study
      of the Liver organized a one-day single-topic consensus conference on HCC.
      Herein, the authors present a summary of the topics covered and the result of
      voting on consensus statements presented at this meeting. 

PMID- 25965438
TI  - Postoperative resource utilization and survival among liver transplant recipients
      with Model for End-stage Liver Disease score >= 40: A retrospective cohort study.
AB  - BACKGROUND: Cirrhotic patients with Model for End-stage Liver Disease (MELD)
      score >= 40 have high risk for death without liver transplant (LT). OBJECTIVE: To
      evaluate these patients' outcomes after LT. METHODS: The present study analyzed a
      retrospective cohort of 519 cirrhotic adult patients who underwent LT at a single
      Canadian centre between 2002 and 2012. Primary exposure was severity of liver
      disease measured by MELD score at LT (>= 40 versus < 40). Primary outcome was
      duration of first intensive care unit (ICU) stay after LT. Secondary outcomes
      were duration of first hospital stay after LT, rate of ICU readmission, re-LT and
      survival rates. RESULTS: On the day of LT, 5% (28 of 519) of patients had a MELD
      score >= 40. These patients had longer first ICU stays after LT (14 versus two
      days; P < 0.001). MELD score >= 40 at LT was independently associated with first
      ICU stay after LT >= 10 days (OR 3.21). These patients had longer first hospital
      stays after LT (45 versus 18 days; P < 0.001); however, there was no significant
      difference in the rate of ICU readmission (18% versus 22%; P = 0.58) or re-LT
      rate (4% versus 4%; P = 1.00). Cumulative survival at one month, three months,
      one year, three years and five years was 98%, 96%, 90%, 79% and 72%,
      respectively. There was no significant difference in cumulative survival
      stratified according to MELD score >= 40 versus < 40 at LT (P = 0.59).
      CONCLUSIONS: Cirrhotic patients with MELD score >= 40 at LT utilize greater
      postoperative health resources; however, they derive similar long-term survival
      benefit from LT.

PMID- 25965439
TI  - Hospital volume and other risk factors for in-hospital mortality among
      diverticulitis patients: A nationwide analysis.
AB  - BACKGROUND: Previous studies have found that a higher volume of colorectal
      surgery was associated with lower mortality rates. While diverticulitis is an
      increasingly common condition, the effect of hospital volume on outcomes among
      diverticulitis patients is unknown. OBJECTIVE: To evaluate the relationship
      between hospital volume and other factors on in-hospital mortality among patients
      admitted for diverticulitis. METHODS: Data from the Nationwide Inpatient Sample
      (years 1993 to 2008) were analyzed to identify 822,865 patients representing
      4,108,726 admissions for diverticulitis. Hospitals were divided into quartiles
      based on the volume of diverticulitis cases admitted over the study period,
      adjusted for years contributed to the dataset. Mortality according to hospital
      volume was modelled using logistic regression adjusting for age, sex, race,
      comorbidities, health care insurance, admission type, calendar year, colectomy,
      disease severity and clustering. Risk estimates were expressed as adjusted ORs
      with 95% CIs. RESULTS: Patients at high-volume hospitals were more likely to be
      admitted emergently, undergo surgical treatment and have more severe disease. In
      hospital mortality was higher among the lowest quartile of hospital volume
      compared with the highest volume (OR 1.13 [95% CI 1.05 to 1.21]). In-hospital
      mortality was increased among patients admitted emergently (OR 2.58 [95% CI 2.40
      to 2.78]) as well as those receiving surgical treatment (OR 3.60 [95% CI 3.42 to
      3.78]). CONCLUSIONS: Diverticulitis patients admitted to hospitals with a low
      volume of diverticulitis cases had an increased risk for death compared with
      those admitted to high-volume centres.

PMID- 25965440
TI  - Prospective evaluation of gastric neurostimulation for diabetic gastroparesis in
      Canada.
AB  - BACKGROUND: The efficacy of gastric neurostimulation therapy for diabetic
      gastroparesis (GP) in a 'real-life' Canadian setting has not been assessed. AIMS:
      To assess changes in health-related quality of life (QoL), weekly vomiting
      frequency (WVF), total symptom score (TSS) and health care utilization 12 months
      before and after gastric neurostimulator implantation in a diabetic GP cohort.
      METHODS: Medication-refractory diabetic GP patients (n=7, four female, mean age
      42 years) were prospectively recruited from 2008 to 2012. QoL scores were self
      administered and obtained at baseline, 24 and 48 weeks postimplantion. WVF and
      TSS were assessed similarly. Health care usage, measured as hospitalization
      frequency and medication cost, was obtained six and 12 months before and after
      implant. Changes from baseline to six and 12 months for all outcomes were
      compared. RESULTS: The mean ( +/- SD) QoL according to EuroQol was significantly
      better at 24 weeks after the baseline measurement (baseline 29 +/- 5, 24 weeks 52
      +/- 7; P = 0.03). The mean improvement in TSS was significantly better at one
      year postintervention (baseline score 35 +/- 5 versus 12 months 27 +/- 3; P =
      0.03). Changes in Short-Form 36 Health Survey and WVF were not significant. Days
      of GP-related hospitalization were highly variable but decreased from a median of
      71 days (range 0 to 227 days) to 29 days (range two to 334 days) one year before
      and after surgery, respectively (P = 0.735). Outpatient medication costs did not
      decrease to a significant extent. CONCLUSION: Gastric neurostimulation for
      diabetic GP appeared to show some beneficial palliative effects overall in the
      present small open-label series, but the effect is highly variable among
      patients, and placebo effect cannot be ruled out.

PMID- 25965441
TI  - Biomarkers as potential treatment targets in inflammatory bowel disease: A
      systematic review.
AB  - There is increasing interest in the concept of 'treat-to-target' in inflammatory
      bowel disease as a mechanism to standardize management and prevent complications.
      While clinical, radiographic and endoscopic treatment end points will figure
      prominently in this promising management paradigm, the role that noninvasive
      biomarkers will play is currently undefined. The goal of the present systematic
      review was to investigate the potential value of biomarkers as treatment targets
      in inflammatory bowel disease, with particular focus on those best studied: serum
      C-reactive protein (CRP) and fecal calprotectin. In Crohn disease, elevated CRP
      levels at baseline predict response to anti-tumour necrosis factor agents, and
      normalization is usually associated with clinical and endoscopic remission. CRP
      and hemoglobin levels can be used to help predict clinical relapse in the context
      of withdrawal of therapy. Ultimately, the authors conclude that currently
      available biomarkers should not be used as treatment targets in inflammatory
      bowel disease because they have inadequate operational characteristics to make
      them safe surrogates for clinical, endoscopic and radiographic evaluation.
      However, CRP and fecal calprotectin are important adjunctive measures that help
      alert the clinician to pursue further investigation. 

PMID- 25965444
TI  - Noninvasive diagnosis of liver fibrosis: The importance of being reimbursed.

PMID- 25965445
TI  - FibroScan(r) access in Canada: Time for reform, a call for universal access.

PMID- 25965442
TI  - Molecular signalling in hepatocellular carcinoma: Role of and crosstalk among
      WNT/beta-catenin, Sonic Hedgehog, Notch and Dickkopf-1.
AB  - Hepatocellular carcinoma is the sixth most common cancer worldwide. In the
      majority of cases, there is evidence of existing chronic liver disease from a
      variety of causes including viral hepatitis B and C, alcoholic liver disease and
      nonalcoholic steatohepatitis. Identification of the signalling pathways used by
      hepatocellular carcinoma cells to proliferate, invade or metastasize is of
      paramount importance in the discovery and implementation of successfully targeted
      therapies. Activation of Wnt/beta-catenin, Notch and Hedgehog pathways play a
      critical role in regulating liver cell proliferation during development and in
      controlling crucial functions of the adult liver in the initiation and
      progression of human cancers. beta-catenin was identified as a protein
      interacting with the cell adhesion molecule E-cadherin at the cell-cell junction,
      and has been shown to be one of the most important mediators of the Wnt
      signalling pathway in tumourigenesis. Investigations into the role of Dikkopf-1
      in hepatocellular carcinoma have demonstrated controversial results, with a
      decreased expression of Dickkopf-1 and soluble frizzled-related protein in
      various cancers on one hand, and as a possible negative prognostic indicator of
      hepatocellular carcinoma on the other. In the present review, the authors focus
      on the Wnt/beta-catenin, Notch and Sonic Hedgehog pathways, and their interaction
      with Dikkopf-1 in hepatocellular carcinoma.

PMID- 25965446
TI  - The Authors respond.

PMID- 25965447
TI  - Translation of questionnaires measuring health related quality of life is not
      standardized: a literature based research study.
AB  - INTRODUCTION: There is growing awareness of the need to explore patient reported
      outcomes in clinical trials. In the Scandinavian Surgical Outcomes Research Group
      we are conducting several clinical trials in cooperation between Danish and
      Swedish surgical researchers, and we use questionnaires aimed at patients from
      both countries. In relation to this and similar international cooperation, the
      validity and reliability of translated questionnaires are central aspects. MAIN
      OBJECTIVES: The purpose of this study was to explore which methodological
      measures were used in studies reporting translation of questionnaires.
      Furthermore, we wanted to make some methodological suggestions for clinical
      researchers who are faced with having to translate a questionnaire. MATERIAL AND
      METHODS: We designed a research study based on a survey of the literature and
      extracted data from published studies reporting the methodological process when
      translating questionnaires on health related quality of life for different
      diseases. RESULTS: We retrieved 187 studies and out of theses we included 52
      studies. The psychometric properties of the translated versions were validated
      using different tests. The focus was on internal validity (96%), reliability
      (67%) criterion validity (81%), and construct validity (62%). For internal
      validity Cronbach's alpha was used in 94% of the studies. CONCLUSIONS: This study
      shows that there seems to be a consensus regarding the translation process
      (especially for internal validity) although most researchers did not use a
      translation guide. Moreover, we recommended that clinical researchers should
      consider three steps covering the process of translation, the qualitative
      validation as well as the quantitative validation.

PMID- 25965448
TI  - Identification of Novel Inhibitors of Mycobacterium tuberculosis PknG Using
      Pharmacophore Based Virtual Screening, Docking, Molecular Dynamics Simulation,
      and Their Biological Evaluation.
AB  - PknG is a Ser/thr protein kinase that plays a crucial role in regulatory
      processes within the mycobacterial cell and signaling cascade of the infected
      host cell. The essentiality of PknG in mycobacterial virulence by blocking
      phagosome-lysosome fusion as well as its role in intrinsic antibiotic resistance
      makes it an attractive drug target. However, only very few compounds have been
      reported as Mycobacterium tuberculosis PknG (MtPknG) inhibitors so far.
      Therefore, in an effort to find potential inhibitors against MtPknG, we report
      here a sequential pharmacophore-based virtual screening workflow, 3-fold docking
      with different search algorithms, and molecular dynamic simulations for better
      insight into the predicted binding mode of identified hits. After detailed
      analysis of the results, six ligands were selected for in vitro analysis. Three
      of these molecules showed significant inhibitory activity against MtPknG. In
      addition, inhibitory studies of mycobacterial growth in infected THP-1
      macrophages demonstrated considerable growth inhibition of M. bovis BCG induced
      through compound NRB04248 without any cytotoxic effect against host macrophages.
      Our results suggest that the compound NRB04248 can be explored for further design
      and optimization of MtPknG inhibitors. 

PMID- 25965449
TI  - Design and Antigenic Epitopes Prediction of a New Trial Recombinant Multiepitopic
      Rotaviral Vaccine: In Silico Analyses.
AB  - Rotavirus is the major etiologic factor of severe diarrheal disease. Natural
      infection provides protection against subsequent rotavirus infection and
      diarrhea. This research presents a new vaccine designed based on computational
      models. In this study, three types of epitopes are considered-linear,
      conformational, and combinational-in a proposed model protein. Several studies on
      rotavirus vaccines have shown that VP6 and VP4 proteins are good candidates for
      vaccine production. In the present study, a fusion protein was designed as a new
      generation of rotavirus vaccines by bioinformatics analyses. This model-based
      study using ABCpred, BCPREDS, Bcepred, and Ellipro web servers showed that the
      peptide presented in this article has the necessary properties to act as a
      vaccine. Prediction of linear B-cell epitopes of peptides is helpful to
      investigate whether these peptides are able to activate humoral immunity.

PMID- 25965450
TI  - Assessing the immunomodulatory role of heteroglycan in a tumor spheroid and
      macrophage co-culture model system.
AB  - The therapeutic benefits of glycans have garnered much attention over the last
      few decades with most studies being reported in 2D cultures or in animal models.
      The present work is therefore aimed to assess the effects of an immunomodulatory
      heteroglycan in a 3D milieu. Briefly, HT29 tumor spheroids were incubated with
      THP-1 macrophages at 1:1 ratio in a culture medium supplemented with immune
      stimulants such as heteroglycans or LPS. Spheroidal distortion, migration of
      tumor cells from the periphery of the spheroids and 46% of higher macrophage
      invasiveness was noted in heteroglycan-treated co-cultures with respect to
      control cultures. Histological sections of the treated co-cultures revealed the
      presence of high apoptotic tumor cells in the spheroidal periphery. CD11c and
      CD68 staining further suggested the predominance of macrophages in the vicinity
      of the apoptotic tumor cells. Such an in vitro created tissue system may thereby
      confirm the effectiveness of heteroglycan in activating the immune cells to
      exhibit tumor cytotoxic properties. 

PMID- 25965451
TI  - Preparation and characterization of CS-g-PNIPAAm microgels and application in a
      water vapour-permeable fabric.
AB  - Chitosan-graft-poly(N-isopropylacrylamide) (CS-g-PNIPAAm) was synthesised using
      sonication with and without the crosslinker, N,N'-methylenebisacrylamide (MBA).
      FTIR, variable-temperature (1)H NMR spectroscopy, atomic force microscopy, UV-vis
      spectrophotometry, differential scanning calorimetry, and dynamic light
      scattering were used to characterize the microgels' chemical constituents,
      structures, morphologies, lower critical solution temperatures (LCSTs), and
      thermo- and pH-responsiveness. The chemical structures of the two CS-g-PNIPAAm
      materials were found to be similar and both exhibited dual responsiveness towards
      temperature and pH. The microgel containing MBA had a higher LCST, smaller
      diameter, and more compact structure, but exhibited opposite pH- and similar
      thermo-responsiveness. Although the structure of the microgel particles prepared
      without crosslinking was unstable, the stability of the crosslinked microgel
      particles enabled them to be finished onto fabric. Because the microgel prepared
      with MBA retains thermosensitivity, it can be used to impart controllable water
      vapour permeability properties. The incorporation of the MBA-crosslinked CS-g
      PNIPAAm microgel particles in cotton fabric was accomplished by a simple pad-dry
      cure procedure from an aqueous microparticle dispersion. The water vapour
      permeation of the finished fabric was measured at 25 and 40 degrees C and 50 and
      90% relative humidities. The finished fabric displayed an obviously high water
      vapour permeability at 40 degrees C. 

PMID- 25965452
TI  - Mannich reaction of polysaccharides: Xylan functionalization in aqueous basic
      medium.
AB  - In this study modification of xylan via Mannich reaction in aqueous basic
      solution to obtain dimethylaminomethylated products and characterization of
      modified xylan were examined. Components were xylan (obtained from corn cob and
      used without modification) as active hydrogen containing compound, formaldehyde
      as carbonyl compound having no alpha-hydrogen and dimethylamine. Mannich reaction
      was used with different parameters such as component concentration, reaction
      temperature, and time. The highest modification was observed about 35 degrees C
      with a nitrogen content of 4.6% by weight indicating successive modification.
      Both 1D and 2D NMR measurements displayed new signals related with aminomethyl
      groups. Spectral characterizations indicated that aminomethylation took place on
      oxygen sites. Moreover modified xylan could form film while xylan could not
      without an auxiliary agent. Antimicrobial activity tests indicated that modified
      xylan acted as a bacteriostatic material. 

PMID- 25965453
TI  - The dramatic effect of small pH changes on the properties of chitosan hydrogels
      crosslinked with genipin.
AB  - We report on intriguing new phenomena related to the creation of chitosan
      hydrogels crosslinked with genipin. We found that the reaction between chitosan
      and genipin is very slow, sometimes requiring more than four days until
      completed. Further, we discovered that altering the pH within the small range of
      4.00-5.50 dramatically affects the reaction, leading to hydrogels differing both
      in appearance and in properties. Increasing the pH by 1.5 units led to an almost
      fourfold decrease in the gelation time and more than tenfold equilibrium
      swelling. A correlation between the percentage of unreacted genipin molecules and
      the hydrogel properties was identified. The strong pH dependency was attributed
      to the degree of chitosan protonation and to the inability of protonated chitosan
      to react with genipin. This research shows, for the first time, that minor
      changes in the pH can lead to substantially different hydrogels.

PMID- 25965454
TI  - Antioxidant activity of polysaccharide purified from Acanthopanax koreanum Nakai
      stems in vitro and in vivo zebrafish model.
AB  - In this study, the antioxidative effects of a purified polysaccharide isolated
      from the stems of Acanthopanax koreanum Nakai (ASP) on hydrogen peroxide-induced
      oxidative stress was investigated both in vitro and in vivo using a zebrafish
      model. A. koreanum Nakai stem was hydrolyzed using five carbohydrases and five
      proteases for the enzyme-assistant extraction. Of the enzyme-assistant extracts,
      the Protamex extract exhibited the highest yield and a potent scavenging activity
      against free radicals. Ethanol-added separation and anion exchange chromatography
      were conducted to identify the active polysaccharide. The purified polysaccharide
      significantly scavenged hydrogen peroxide and reduced hydrogen peroxide-induced
      cell death in Vero cells and in zebrafish. The results reveal that ASP is a
      useful antioxidant polysaccharide and might be available for relevant industrial
      applications. 

PMID- 25965455
TI  - Dispersion of halloysite loaded with natural antimicrobials into pectins:
      Characterization and controlled release analysis.
AB  - This paper reports the preparation and characterization of green composites based
      on pectins and nano-hybrids composed of halloysite nanotubes (HNTs) loaded with
      rosemary essential oil. Different hybrid percentages were mixed into a pectin
      matrix, by ball milling in the presence of water. Cast films were obtained and
      analyzed. Structural organization and physical properties (thermal, mechanical,
      barrier to water vapor) were correlated to the nano-hybrid content. A preliminary
      study on the kinetics of release of the rosmarinic acid, chosen as a model
      molecule, was also performed. This work showed the potential of these systems in
      the active packaging field where controlled release of active species is
      required. 

PMID- 25965456
TI  - Biochemical evaluation of xylanases from various filamentous fungi and their
      application for the deinking of ozone treated newspaper pulp.
AB  - Filamentous fungi, Aspergillus oryzae MDU-4 was biochemically selected among
      different species of Aspergillus and Trichoderma, for xylanase production. The
      enzyme activity and specific activity of partially purified xylanase from A.
      oryzae MDU-4 was 7452 IU/ml and 13,549 IU/g, respectively. Temperature and pH
      optima for xylanase were found to be 60 degrees C and 6.0, respectively. The
      reaction kinetics of xylanase was found to be Km (3.33 mg/ml) and Vmax (18,182
      MUmol/mg). The implementation of ozone treatment in the deinking of newspaper
      pulp resulted in high crystallinity index (72.1%) and more fibrillar surface.
      Furthermore, the xylanase treated pulp showed significant improvement in optical
      properties such as brightness (57.9% ISO) and effective residual ink
      concentration (211 ppm). Scanning electron microscopy analysis suggests
      perforations in xylanase treated pulp samples. Here we report biochemical
      evaluation of xylanases and a combination of ozone treatment followed by
      catalytically efficient fungal xylanase selected for the cost competitive
      deinking of newspaper pulp.

PMID- 25965457
TI  - Kinetics and functional effectiveness of nisin loaded antimicrobial packaging
      film based on chitosan/poly(vinyl alcohol).
AB  - The aim of this study was to evaluate the kinetics and functional effectiveness
      of Nisin loaded chitosan/poly(vinyl alcohol) (Nisin-CS/PVA) as an antibacterial
      packaging film. The films were prepared by coating method and Staphylococcus
      aureus (S. aureus, ATCC6538) was used as test bacterium. The intermolecular
      hydrogen bonds between CS and PVA molecules were confirmed. The elasticity of
      films was significantly improved by the incorporation of PVA, and the film could
      also bear a relative high tensile strength at 26.7 MPa for CS/PVA=1/1. As CS/PVA
      ratio decreased, the water vapor permeability (WVP) decreased and reached its
      minimum value 0.983 * 10(-10)gm(-1)s(-1) at CS/PVA=1/1, meanwhile, oxygen
      permeability (OP) increased but still lower than 0.91 cm(3) MUm m(-2)d(-1)kPa(-1)
      for CS/PVA=1/1 as the CS/PVA ratio was above 1:1. The initial diffusion of nisin
      (Mt/M infinity < 2/3) from CS/PVA film could be well described by the Fickian
      diffusion equation. Owing to the positively charged nisin at pH below isoelectric
      point (pI, 8.8) and its increasing dissolubility in water as the pH reduced, the
      diffusion of nisin from the films strongly depended on pH and ionic strength
      besides CS/PVA ratio and temperature. Moreover, the thermodynamic parameters
      suggested the spontaneous and endothermic diffusion of nisin from the films. The
      resulting data can provide some valuable information for the design of film in
      structure and ingredient.

PMID- 25965458
TI  - Polarity functions' characterization and the mechanism of starch modification by
      DC glow discharge plasma.
AB  - The wheat starch was investigated, before and after exposure to the argon and
      oxygen glow discharge plasma, without any added chemical reagents, using a novel
      media polarity functions method. The mechanisms of modification of starch in
      plasma discharge irradiation were explained using some methods such as; NMR, IR
      spectroscopy, Kamlet-Abboud-Taft polarity functions (specific and nonspecific
      interaction) of modified starch. The starch modification, by plasma treatment,
      shows valuable changes with plasma gas and relative ionized or active species.
      Characterizations indicate that argon glow discharge plasma increases crosslink
      in C-2 site of starch. Also, oxygen plasma discharge irradiation tends to oxidize
      the OH group in C-6 site of carbonyl group. Furthermore, the reported mechanisms
      show the highest efficiency, because of the stereo-chemical orientation of active
      sites of starch and plasma potential of wall in plasma media. 

PMID- 25965459
TI  - Toughening polylactide with polyether-block-amide and thermoplastic starch
      acetate: Influence of starch esterification degree.
AB  - Native corn starch was esterified with acetic anhydride and plasticized with
      glycerol to give the thermoplastic starch acetate (TPSA). TPSA was blended with
      polylactide (PLA) and polyether-block-amide-graft-glycidyl methacrylate (PEBA-g
      GMA) to obtain biodegradable PLA/PEBA-g-GMA/TPSA blends with high notched impact
      resistance and low cost. Compared with PLA/PEBA-g-GMA blends, as much as 9 wt%
      expensive PEBA-g-GMA elastomer could be substituted by the slightly acetylated
      thermoplastic starch while retaining high impact strength. The mechanical
      properties depended on the esterification degree of starch acetate. The impact
      strength, tensile strength and elongation at break increased to the peak value
      with increasing the esterification degree from 0 to 0.04, thereafter they
      decreased on further increasing the esterification degree. The morphological
      results showed that the TPSA particles were smaller and more uniform at the
      optimum esterification degree of 0.04, leading to the peak value of the
      mechanical properties.

PMID- 25965460
TI  - Bacterial cellulose-poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate)
      composites for optoelectronic applications.
AB  - Electrically conducting bacterial cellulose (BC) membranes were prepared by ex
      situ incorporation of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (
      PEDOT: PSS) into BC pellicles. The BC pellicles were immersed into an aqueous
      solution of PEDOT: PSS for 6, 12, 18, or 24h, and the resultant composites were
      vacuum dried at ambient temperature. The structural features of the composites
      were determined using X-ray photoelectron spectroscopy (XPS), field-emission
      scanning electron microscopy (FE-SEM), Fourier-transform infrared (FTIR)
      spectroscopy, and X-ray diffraction (XRD). XPS confirmed synthesis of the
      composites, and SEM showed uniform incorporation of PEDOT: PSS into the BC
      matrix. The FTIR spectra of the composites exhibited characteristic bands for
      both BC and PEDOT: PSS, and XRD analysis showed a slight decrease in
      crystallinity during composite preparation. The electrical conductivity of the
      composites was 12.17S/cm for incorporation of 31.24 wt% PEDOT: PSS into the BC
      matrix. These highly conducting BC-PEDOT:PSS composites are expected to find
      potential applications in optoelectronic devices such as biosensors, organic
      light-emitting diodes, and solar cells.

PMID- 25965461
TI  - Isolation, purification and structural characterization of polysaccharide from
      Acanthopanax brachypus.
AB  - A water-soluble polysaccharide, designated as ABPS-21, was isolated from the stem
      barks of Acanthopanax brachypus by hot-water extraction and purified by Cellulose
      DEAE-52 and Sephacryl S-300 HR gel-filtration chromatography, respectively. The
      homogeneity and molecular weight were determined using HPGPC. The structure was
      elucidated based on monosaccharide composition and methylation analysis, partial
      acid hydrolysis, periodate oxidation, Smith degradation, IR and NMR spectroscopy.
      The result showed that ABPS-21 was a homogeneous heteropolysaccharide including
      galactose, glucose, rhamnose and galacturonic acid in a molar ratio of
      3.0:2.0:2.0:1.0, respectively, with an average molecular weight of 1.06 *
      10(5)Da. The main chain of ABPS-21 was made up of -> 4)-beta-D-Galp-(1 -> 4)-beta
      D-Glcp-(1 -> 4)-beta-D-Galp-(1 -> 4)-beta-D-Galp-(1 -> 2)-alpha-L-Rhap-(1 ->, and
      two side chains alpha-l-Rhap-(1 -> 4)-beta-D-Glcp-(1 -> and alpha-D-galpA-(1 ->
      were attached to the backbone chain at O-6 position of 1,4,6-linked beta-D-Glcp
      and 1,4,6-linked beta-D-Galp, respectively. ABPS-21, an acidic branched
      polysaccharide from A. brachypus, was not described up to now.

PMID- 25965462
TI  - Preparation and characterization of sodium carboxymethyl cellulose/cotton linter
      cellulose nanofibril composite films.
AB  - Crystalline cellulose nanofibril (CNF) was isolated from cotton linter pulp using
      an acid hydrolysis method and used as a filler to reinforce sodium carboxymethyl
      cellulose (CMC) film. The CNF was in rod shape with the diameter of 23-38 nm and
      the length of 125-217 nm and crystallinity index (CI) was 0.89. The effect of CNF
      concentration (1, 3, 5, and 10 wt% based on CMC) on the optical, morphological,
      mechanical, water vapor barrier, surface hydrophobicity, and thermal properties
      of the nanocomposites were studied. The CNF was evenly distributed in the polymer
      matrix to form smooth and flexible films indicating the CNF is highly compatible
      with the CMC. The tensile strength (TS) and elastic modulus (EM) of CMC film
      increased by 23% and 27%, respectively, while the elongation (E) decreased by 28%
      with 5 wt% of CNF inclusion. The WVP of CMC film decreased at low content of CNF,
      and increased with increase in CNF content, then decreased but to the same level
      of the control CMC film with the inclusion of 10 wt% of CNF. Transparency of CMC
      film decreased slightly from 87.7% to 86.2% with 5 wt% of CNF. The CMC/CNF
      composite films have a high potential to be used as an edible coating or
      packaging films for the extension of shelf life of fresh and minimally processed
      fruits and vegetables.

PMID- 25965463
TI  - Properties of cellulose/Thespesia lampas short fibers bio-composite films.
AB  - Cellulose was dissolved in pre cooled environment friendly solvent (aq.7% sodium
      hydroxide+12% urea) and regenerated with 5%H2SO4 as coagulation bath. Using
      cellulose as matrix and alkali treated short natural fibers extracted from the
      newly identified Thespesia lampas plant as fillers the green composite films were
      prepared. The films were found to be non toxic. The effect of fiber loading on
      the tensile properties and thermal stability was studied. The fractographs
      indicated better interfacial bonding between the fibers and cellulose. The
      crystallinity of the composite films was found to be lower than the matrix and
      decreased with increasing fiber content. In spite of better interfacial bonding,
      the tensile properties of the composites were found to be lower than those of the
      matrix and decreased with increasing fiber content and this behavior was
      attributed to the random orientation of the fibers in the composites. The thermal
      stability of the composite films was higher than the matrix and increased with
      fiber content. 

PMID- 25965464
TI  - Characterization of the time evolution of starch structure from rice callus.
AB  - Callus (formed when a plant tissue is wounded) is a promising system for studying
      starch biosynthesis and bioengineering; however the molecular structure of callus
      starch has been poorly characterized. Size-exclusion chromatography was used in
      this study to characterize the starch structure in rice calli from two cultivars
      and a mutant of one cultivar lacking starch branching enzyme IIb. There were
      major qualitative differences in the chain-length and whole-molecule size
      distributions between starch from grain and from callus. However callus starch
      was found to be able to simulate the starch metabolism from both leaves and
      endosperm and reveal the structural development of starch granules, and this was
      dependent on the culture system. During synthesis, trans-lamellar amylopectin
      chains in callus are synthesized earlier than single-lamella chains, while
      enzymatic degradation starts from outer to inner amylopectin chains. The outer
      layers of the callus-starch granules have larger molecules with lower amylose
      content and shorter amylopectin chains compared to further inside the callus
      starch granules. Controlling starch granular number and size thus has potential
      for improving both the quantity and quality of plant starch. 

PMID- 25965465
TI  - Utilization of olive tree branch cellulose in synthesis of hydroxypropyl
      carboxymethyl cellulose.
AB  - This paper describes the functionalization of cellulose extracted from olive tree
      branches by subjecting it to successive etherification reactions,
      hydroxypropylation and carboxymethylation. Factors affecting the efficiency of
      etherification reactions like propylene oxide concentration, alkali
      concentration, reaction temperature and reaction duration were studied. The
      etherification efficiency was evaluated by analyzing the mixed cellulose ether to
      estimate its molar substitution and degree of substitution. Optimum conditions
      for hydroxypropylation reaction are to use 10% NaOH, together with 115% propylene
      oxide (all based on weight of cellulose), at 60 degrees C for 120 min. The
      obtained samples were characterized by estimating the molar substitution and the
      best value suitable for water solubility (0.39) was attained upon using the above
      optimum conditions. Optimum conditions for carboxymethylation of the
      hydroxypropylated cellulose were to use 20% (w/v) from NaOH during the
      alkalization step. This optimum condition gave carboxymethylated sample having
      degree of substitution 0.4 which is suitable for water solubility.

PMID- 25965466
TI  - Water proof and strength retention properties of thermoplastic starch based
      biocomposites modified with glutaraldehyde.
AB  - Water proof and strength retention properties of thermoplastic starch (TPS)
      resins were successfully improved by reacting glutaraldehyde (GA) with starch
      molecules during their gelatinization processes. Tensile strength (sigmaf) values
      of initial and aged TPS100BC0.02GAx and (TPS100BC0.02GAx)75PLA25 specimens
      improved significantly to a maximal value as GA contents approached an optimal
      value, while their moisture content and elongation at break values reduced to a
      minimal value, respectively, as GA contents approached the optimal value. The
      sigmaf retention values of (TPS100BC0.02GA0.5)75PLA25 specimen aged for 56 days
      are more than 50 times higher than those of corresponding aged TPS and
      TPS100BC0.02 specimens, respectively. New melting endotherms and diffraction
      peaks of VH-type starch crystals were found on DSC thermograms and WAXD patterns
      of aged TPS or TPS100BC0.02 specimens, respectively, while negligible
      retrogradation effect was found for most aged TPS100BC0.02GAx and/or
      (TPS100BC0.02GAx)75PLA25 specimens.

PMID- 25965467
TI  - Isolation, structural characterization and neurotrophic activity of a
      polysaccharide from Phellinus ribis.
AB  - A new polysaccharide named PRG was isolated from the fruiting bodies of Phellinus
      ribis by hot water extraction, ethanol precipitation, anion-exchange and gel
      filtration chromatography. PRG was homogeneous, with a molecular weight of 5.16 *
      10(3)Da, as determined by high-performance size-exclusion chromatography
      multiangle laser light scattering analysis. Its structural characteristics were
      investigated and elucidated by methylation analysis, partial acid hydrolysis, gas
      liquid chromatography mass spectrometry, Fourier transform infrared and nuclear
      magnetic resonance spectroscopy. Based on obtained data, PRG was found to be a
      beta-d-glucan containing a (1 -> 3)-linked backbone, with a branch of two (1 ->
      6)-linked and one terminal glucoses substituting at the C-6 position every three
      residues, along the main chain. PRG exhibited neurotrophic activity, which
      significantly promoted the neurite outgrowth of the nerve growth factor
      stimulated PC12 cells, suggesting that it might be a potential candidate for the
      treatment of neurodegenerative diseases.

PMID- 25965468
TI  - Hydrated fractions of cellulosics probed by infrared spectroscopy coupled with
      dynamics of deuterium exchange.
AB  - This article presents a novel method to selectively probe the non-crystalline,
      hydrated fractions of cellulosic biomass. The method is based on time-resolved
      infrared spectra analyzed to provide information on spectral and dynamical
      features of deuterium exchange (OH -> OD) in D2O atmosphere. We assign deuterium
      exchange spectral regions (700-3800 cm(-1)) and explore changes due to relative
      humidity, different cellulosic samples, and infrared polarization. Here, two
      results are highlighted. First, a wide range of celluloses isolated from plants
      show remarkable spectral similarities whatever the relative amounts of cellulose
      and xylan. This result supports an inherent type of hydrated disorder which is
      mostly insensitive to the molecular identities of the associated polysaccharides.
      Second, polarized infrared analysis of cotton reveals hydrated cellulose having
      chains preferentially aligned with those of crystals, while the hydroxyls of
      hydrated cellulose present much more randomized orientation. Our results provide
      new insights on molecular and group orientation and on hydrogen bonding in
      hydrated fractions of cellulosic biomass.

PMID- 25965469
TI  - Starch transitions of different gluten free flour doughs determined by dynamic
      thermal mechanical analysis and differential scanning calorimetry.
AB  - Gluten-free flour doughs (three from different maize varieties and one from
      chestnut fruit) processed at the same consistency level (1.10 +/- 0.07 N m) with
      different water absorption were used to determine the starch transitions by means
      of two different experimental techniques, differential scanning calorimetry (DSC)
      and dynamic thermal mechanical analysis (DMTA). The ranges of temperatures of
      gelatinization (G), amylopectin melting (M1), amylose-lipid complexes melting
      (M2) and amylose melting (M3) for all tested flour doughs were determined by both
      experimental techniques with acceptable agreement between them. The starch
      transitions in DMTA were determined by means of the elastic modulus (G, M1 and
      M2) or damping factor (G, M3) evolution with temperature. The temperatures and
      enthalpies of the transitions depended on water content, the nature and
      characteristics (mainly damaged starch) of the starch and the presence of other
      compounds (mainly lipid and sugars) in the flour doughs.

PMID- 25965470
TI  - Improvement of emulsifying properties of oat protein isolate-dextran conjugates
      by glycation.
AB  - In order to improve the emulsifying properties of oat protein, oat protein
      isolate (OPI)-dextran (Dex) conjugates were prepared by glycation reaction.
      Emulsifying properties of emulsions stabilized by native OPI (OPIN), OPI-Dex
      conjugates (ODC) and heated OPI (OPIH) were characterized by zeta-potential, mean
      droplet size and microstructure. The results showed that the covalent attachment
      of OPI and dextran was confirmed by determining degree of graft and SDS-PAGE. OPI
      Dex conjugates were capable of forming a finer emulsion, which exhibited smaller
      average particle size and better storage stability under different homogenization
      pressures (30, 60, 90 MPa) compared with OPIN and OPIH. When assessed in
      different pH and ionic strength, emulsions stabilized by OPI-Dex conjugates
      resulted in improved emulsion stability to environmental stresses. Confocal laser
      scanning microscopy depicted more uniform and smaller oil droplets that had a
      reduced tendency to coalesce for emulsions prepared with ODC.

PMID- 25965471
TI  - Effect of drying methods on physicochemical properties and antioxidant activities
      of wolfberry (Lycium barbarum) polysaccharide.
AB  - In this study, an efficient drying process of Lycium barbarum L. polysaccharide
      (LBP) suitable for industrial production was developed and optimized. Three
      drying methods, including hot air drying (40-80 degrees C), vacuum drying (40-60
      degrees C) and spray drying were test and compared. Hot air drying and vacuum
      drying cost long time and produced a brown product which needs further process
      due to the agglomeration or alveolation form. The condition of spray drying
      (without any excipient) was optimized by orthogonal experiment, which gave
      different optimum conditions based on LBP recovery rate (LBP solution
      concentration 1.06 g/mL, inlet air temperature 170 degrees C, sample flow rate 15
      mL/min and air speed 4.2m(3)/min) or LBP transparency (LBP solution concentration
      1.04 g/mL, inlet air temperature 170 degrees C, sample flow rate 20 mL/min and
      air speed 2.8m(3)/min). Pilot scale experiments showed preferable stability of
      LBP product quality and process parameters. Sample of spray drying (SD) had the
      highest scavenging free radical effects, the best appearance (LBP transparency),
      and uniform morphology with hollow sphere which are important properties for the
      reconstitution of the powder product. Considering the product appearance and
      product activity, the spray drying was selected to apply in industrial
      production.

PMID- 25965472
TI  - Influence of pH on mechanical relaxations in high solids LM-pectin preparations.
AB  - The influence of pH on the mechanical relaxation of LM-pectin in the presence of
      co-solute has been investigated by means of differential scanning calorimetry,
      zeta-potential measurements and small deformation dynamic oscillation in shear.
      pH was found to affect the conformational properties of the polyelectrolyte
      altering its structural behavior. Cooling scans in the vicinity of the glass
      transition region revealed a remarkable change in the viscoelastic functions as
      the polyelectrolyte rearranges from extended (neutral pH) to compact
      conformations (acidic pH). This conformational rearrangement was experimentally
      observed to result in early vitrification at neutral pH values where dissociation
      of galacturonic acid residues takes place. Time-temperature superposition of the
      mechanical shift factors and theoretical modeling utilizing WLF kinetics
      confirmed the accelerated kinetics of glass transition in the extended pectin
      conformation at neutral pH. Determination of the relaxation spectra of the
      samples using spectral analysis of the master curves revealed that the relaxation
      of macromolecules occurs within ~ 0.1s regardless of the solvent pH.

PMID- 25965473
TI  - Packaging performance of organic acid incorporated chitosan films on dried
      anchovy (Stolephorus indicus).
AB  - Antimicrobial chitosan films were prepared with acetic acid and propionic acid
      with glycerol as plasticizer and its efficiency was compared with polyester
      polyethylene laminate (PEST/LDPE). The tensile strength of acetic acid/chitosan
      (ACS) films were higher than propionic acid/chitosan (PCS) films. The elongation
      percentage (6.43-11.3) and water vapour permeability (0.015-0.03 g/m(2)/day) were
      significantly lower (p<0.05) for chitosan films when compared to control. Oxygen
      transmission rate (OTR) of control and propionic acid/chitosan (PCS) films were
      significantly higher (p<0.05) than acetic acid/chitosan (ACS) films. Dried
      anchovy (Stolephorus indicus) wrapped in these films were stored at ambient
      temperature for three months. Quality indices like peroxide value (PV),
      thiobarbituric acid value (TBA) and microbiological parameters such as aerobic
      plate count (APC) and total fungal count (TFC) were periodically determined. In
      terms of microbial and chemical indices, anchovies wrapped in ACS and PCS films
      were superior to those wrapped with PEST/LDPE films during storage. Study
      revealed the suitability of chitosan film as wraps for increasing storage
      stability of dried fish.

PMID- 25965474
TI  - Effect of the addition order and amylose content on mechanical, barrier and
      structural properties of films made with starch and montmorillonite.
AB  - This study considered the effect of amylose content (30% and 70%),
      montmorillonite (MMT) fraction (5 and 15%) and preparation method on mechanical
      and barrier properties of starch/clay nanocomposites prepared by casting. In
      Method 1, (30% w/w) glycerol was incorporated before starch gelatinization and
      MMT addition, while in Method 2 after gelatinization and MMT addition.
      Nanocomposites with higher amount of MMT showed the highest tensile strength and
      Young's modulus for both preparation methods. Method 1 favored nanocomposite
      properties of films with less amylose content, meanwhile Method 2 favored
      nanocomposites properties with higher amylose content. Water vapor permeability
      did not decrease significantly in starch films with different amylose content
      with the two different preparation methods. X-ray diffraction of the starch films
      indicated intercalated structures. Higher melting temperature (Tm) was found for
      nanocomposites with Method 2, indicating more ordered structures. Films with 70%
      amylose content have higher Tm than films with 30% amylose. 

PMID- 25965475
TI  - Cellulose nanocrystals isolated from oil palm trunk.
AB  - In this study cellulose nanocrystals were isolated from oil palm trunk (Elaeis
      guineensis) using acid hydrolysis method. The morphology and size of the
      nanocrystals were characterized using scanning electron microscopy and
      transmission electron microscopy. The results showed that the nanocrystals
      isolated from raw oil palm trunk (OPT) fibers and hot water treated OPT fibers
      had an average diameter of 7.67 nm and 7.97 nm and length of 397.03 nm and 361.70
      nm, respectively. Fourier Transform Infrared spectroscopy indicated that lignin
      and hemicellulose contents decreased. It seems that lignin was completely removed
      from the samples during chemical treatment. Thermogravimetric analysis
      demonstrated that cellulose nanocrystals after acid hydrolysis had higher thermal
      stability compared to the raw and hot water treated OPT fibers. The X-ray
      diffraction analysis increased crystallinity of the samples due to chemical
      treatment. The crystalline nature of the isolated nanocrystals from raw and hot
      water treated OPT ranged from 68 to 70%.

PMID- 25965476
TI  - Characterization and antioxidant activities of acidic polysaccharides from
      Gynostemma pentaphyllum (Thunb.) Markino.
AB  - Three acid polysaccharides obtained from Gynostemma pentaphyllum (Thunb.) Markino
      (named as GPA1, GPA2 and GPA3) using combination of water extraction, ion
      exchange and gel permeation chromatography were subjected to composition analysis
      and valuated for the antioxidant activity. The sugar content of GPA1, GPA2 and
      GPA3 were 54.55%, 85.70% and 91.34%, respectively. Monosaccharide analysis showed
      that GPA1, GPA2 and GPA3 were all composed of Man, Rha, GlcA, GalA, Glc, Gal, Ara
      and Fuc, besides, GPA2 and GPA3 also contained Xyl. The molecular weight of GPA1,
      GPA2 and GPA3 were 19.6kDa, 10.6 kDa and 6.7 kDa, respectively. In vitro
      antioxidant assay, GPA1, GPA2 and GPA3 could scavenge 1, 1-diphenyl-2
      picrylhydrazyl (DPPH) radical and hydroxyl radical, chelate ferrous ion and
      reduce ferric ion. The antioxidant activities of GPA3 were stronger than those of
      GPA1 and GPA2, suggesting that GPA3 has significant potential as a natural
      antioxidant agent.

PMID- 25965477
TI  - Extraction, characterization of a Ginseng fruits polysaccharide and its immune
      modulating activities in rats with Lewis lung carcinoma.
AB  - In this study, one polysaccharide (GFP1), with an average molecular weight of 1.4
      * 10(5)Da, was isolated from Ginseng fruits. GFP1 was composed of galactose,
      glucose, rhamnose, and arabinose in a molar ratio of 6.1:2.0:1.1:3.2, and had a
      backbone mainly consisting of (1 -> 6)-linked-Galp, (1 -> 3,6)-linked-Galp and (1
      -> 3,6)-linked-Glcp residues, which was terminated with terminal (1 ->)-linked
      Araf or -Rhap attached to O-3 position of (1 -> 3,6)-linked-Galp and (1 -> 3,6)
      linked-Glcp. We also evaluated the effect of GFP1 on anti-tumor immune response
      in Lewis lung carcinoma (LLC)-bearing mouse model and explored the possible
      mechanism. GPF1 could significantly inhibit tumor growth and lung metastasis in
      vivo, increase the relative spleen and thymus weight, promote ConA or LPS-induced
      spleen lymphocytes proliferation, elevate the activities of NK cell in spleen,
      and increase the serum concentration of interleukin-2 (IL-2) and interferon-gamma
      (IFN-gamma), as well as the ratio of CD4(+)/CD8(+) in LLC-bearing mice. All these
      findings implied that GFP1 could effectively inhibit tumor growth and lung
      metastasis via activating immune function and provide insights into the mechanism
      of GFP1 in the prevention and treatment of lung cancer.

PMID- 25965478
TI  - Coaxial nanofibers of chitosan-alginate-PEO polycomplex obtained by
      electrospinning.
AB  - Electrospinning of mucoadhesive membranes is a new and promising field of
      investigation in the pharmaceutical and biomedical area. The present study
      explored the electrospinning of two mucoadhesive polymers, chitosan and alginate,
      to form a core-shell type nanofibers for future applications as controlled drug
      delivery. Due to the charged functional groups present in these natural
      polysaccharides, they can complex to yield various nanodevices to be used in
      controlled release of several active ingredients. In this work, the core-shell
      type coaxial nanofibers formation was evidenced by the aid of transmission
      electron microscopy (TEM). Other characterization techniques as scanning electron
      microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetric
      analysis (TGA), Infrared spectroscopy (FTIR) and X-ray diffraction (XRD),
      strongly suggest the formation of different molecular structures of the membranes
      obtained by the complexation of chitosan and alginate. Swelling rate and weight
      loss tests followed by SEM analyses confirmed that the nanofiber structure of
      these membranes were kept even after incubating them for 24h in water. The
      results of this work confirmed that core-shell nanofibers made of chitosan and
      alginate polycomplex is possible to be obtained with success. 

PMID- 25965479
TI  - Thermoset nanocomposites from waterborne bio-based epoxy resin and cellulose
      nanowhiskers.
AB  - Thermoset nanocomposites were prepared from a waterborne terpene-maleic ester
      type epoxy resin (WTME) and cellulose nanowhiskers (CNWs). The curing behaviors
      of WTME/CNWs nanocomposites were measured with rotational rheometer. The results
      show that the storage modulus (G') of WTME/CNWs nanocomposites increased with the
      increase of CNWs content. Observations by scanning electron microscopy (SEM)
      demonstrate that the incorporation of CNWs in WTME matrix caused microphase
      separation and destroyed the compactness of the matrix. This effect leads to the
      glass transition temperatures (Tg) of WTME/CNWs nanocomposites slightly decrease
      with the increase of CNWs content, which were confirmed by both DSC and DMA
      tests. The mechanical properties of WTME/CNWs nanocomposites were investigated by
      tensile testing. The Yong's modulus (E) and tensile strength (sigmab) of the
      nanocomposites were significantly reinforced by the addition of CNWs. These
      results indicate that CNWs exhibit excellent reinforcement effect on WTME matrix,
      due to the formation and increase of interfacial interaction by hydrogen bonds
      between CNWs nano-filler and the WTME matrix. 

PMID- 25965480
TI  - Homogeneous tosylation of agarose as an approach toward novel functional
      polysaccharide materials.
AB  - The homogeneous tosylation of agarose was studied with respect to the effects of
      reaction parameters, such as reaction medium, time, and molar ratio, on the
      reaction course, the degree of substitution (DS) with tosyl/chloro deoxy groups,
      and the molecular structure. Tosyl agaroses (TOSA) with DS tosyl <= 1 .81 could
      be obtained in completely homogeneous reactions by using N,N-dimethylacetamide
      (DMA)/LiCl or 1,3-dimethyl-2-imidazolidinone (DMI) as solvents. The products were
      characterized by FT-IR and NMR spectroscopy and it was demonstrated that two
      types of substitution pattern can be achieved: (i) non-preferential substitution
      at position 6 of the 1 -> 3-linked beta-d-galactose unit (G-6) and position 2 of
      the 1 -> 4-linked 3,6-anyhdro-alpha-L-galactose unit (LA-2) and (ii)
      regioselective tosylation at G-6, depending on whether the reaction is performed
      with or without LiCl. Finally, the nucleophilic displacement reaction of TOSA was
      studied using azide and ethylenediamine as representative nucleophiles. Novel
      deoxy-agarose derivatives were obtained that showed an interesting solubility
      behavior and will be used for creating functional polysaccharide materials.

PMID- 25965481
TI  - Physicochemical characterization of novel Schiff bases derived from developed
      bacterial cellulose 2,3-dialdehyde.
AB  - The synthesis of two novel Schiff's bases (cellulose-2,3-bis-[(4-methylene-amino)
      benzene-sulfonamide] (5) & cellulose-2,3-bis-[(4-methylene-amino)-N-(thiazol-2
      yl)-benzenesulfonamide] (6) via condensation reactions of periodate oxidized
      developed bacterial cellulose ODBC (2) with sulfa drugs [sulfanilamide (3) &
      sulfathiazole (4)] was reported. The physicochemical characterization of the
      condensation products was performed using FTIR, (1)H NMR, (13)C NMR spectral
      analyses, X-ray diffraction and DTA. The ODBC exhibited the highest degree of
      oxidation based on the aldehyde group number percentage (82.9%), which confirms
      the highest reactivity of developed bacterial cellulose [DBC (1)]. The X-ray
      diffractograms indicated an increase in the interplanar distance of the cellulose
      Schiff base (6) compared to ODBC (2) due to sulfathiazole (4) inclusion between
      ODBC (2) sheets corresponding to the 1 1 0 plane. In addition, the aldehyde
      content of Schiff base (6) was (20.8%) much lower than that of Schiff base (5)
      (41.5%). These results confirmed the high affinity of sulfathiazole (4) to the
      ODBC (2) chain, and the substantial changes in the original properties of ODBC
      were due to these chemical modifications rather than the sulfanilamide (3).

PMID- 25965482
TI  - Saffron and beetroot extracts encapsulated in maltodextrin, gum Arabic, modified
      starch and chitosan: Incorporation in a chewing gum system.
AB  - Maltodextrin (MD-21DE), gum Arabic (GA), gum Arabic-modified starch (GA-MS),
      modified starch-chitosan (MS-CH) and modified starch-maltodextrin-chitosan (MS-MD
      CH) were used as agents for beetroot and saffron coloring-extracts
      microencapsulation by freeze drying. The produced powders were evaluated in terms
      of coloring strength (E) during storage at 40 degrees C for 10 weeks and a first
      order kinetic was applied. Color parameters (L(*), a(*), b(*), C(*) and
      DeltaE(*)) and water sorption behavior was also studied. Moreover, incorporation
      of the powders in a chewing gum model system was conducted. The type of
      encapsulating agent significantly (P<0.05) affected the studied parameters with
      the order of protection in both extracts being as follows: MD>GA>GA-MS>MS-CH>MS
      MD-CH. The water sorption study revealed that MD and GA kept their structural
      integrity up to water activities of 0.66 and 0.82, respectively. The chewing gum
      samples produced with coloring extracts encapsulated in GA-MS showed the greatest
      a(*)(for beetroot) and b(*) (for saffron) values indicating a better protection. 

PMID- 25965483
TI  - Roles of GBSSI and SSIIa in determining amylose fine structure.
AB  - This study examines the relationships between genetics (single nucleotide
      polymorphisms (SNPs) in GBSSI and SSIIa genes), starch structure (amylose and
      amylopectin fine structures), and starch properties (relating to gelatinization).
      GBSSI and SSIIa SNPs did not alter the starch content of rice grains. GBSSI SNPs
      can affect the amylose content, but they are incapable of altering the chain
      lengths of amylopectin and amylose. The amounts of both long and short amylose
      branches changed with the same trend as amylose content, and they appeared to
      affect starch gelatinization properties. SSIIa synthesizes intermediate single
      lamella amylopectin chains (DP 16-21), and consequently impacts the
      gelatinization temperature. Mathematical modelling suggests that the reduction in
      SSIIa activity significantly increases the activity of SBEII, resulting in a
      decreased activity ratio of SS to SBE in the enzyme set governing an appropriate
      chain-length distribution range. This application of the genetics-structure
      property paradigm provides selection strategies to produce rice varieties with
      improved qualities. 

PMID- 25965484
TI  - Synthesis, characterization and application of novel cationic and amphoteric
      flocculants based on amylopectin.
AB  - The synthesis of novel cationic flocculants based on amylopectin (AP), acrylamide
      (AM) and (3-acrylamidopropyl) trimethylammonium chloride (ATMAC) were done by
      free radical polymerization using ammonium persulphate (APS) as an initiator.
      Three different grades of novel cationic flocculants (AP-g-C 1 to AP-g-C 3) were
      synthesized by varying the proportion of acrylamide and (3-acrylamidopropyl)
      trimethylammonium chloride monomers. Through the hydrolysis of these flocculants,
      in presence of NaOH, three different grades of amphoteric polymers (AP-AT-C 1 to
      AP-AT-C 3) were synthesized. The synthesized polymers were characterized by
      various methods, namely, infrared spectroscopy, NMR spectroscopy, thermal
      analysis, viscosity measurement, scanning electron microscopy and X-ray
      diffractometry. The flocculation performance of AP-g-C and AP-AT-C were studied
      in kaolin suspension using jar test and settling test methods at neutral pH. Dye
      (Methylene blue) removal tests were performed using polymer beads and analysed by
      UV-vis spectroscopy. 

PMID- 25965485
TI  - Active bilayer films of thermoplastic starch and polycaprolactone obtained by
      compression molding.
AB  - Bilayer films consisting of one layer of PCL with either one of thermoplastic
      starch (S) or one of thermoplastic starch with 5% PCL (S95) were obtained by
      compression molding. Before compression, aqueous solutions of ascorbic acid or
      potassium sorbate were sprayed onto the S or S95 layers in order to plasticize
      them and favor layer adhesion. S95 films formed bilayers with PCL with very good
      adhesion and good mechanical performance, especially when potassium sorbate was
      added at the interface. All bilayers enhanced their barrier properties to water
      vapour (up to 96% compared to net starch films) and oxygen (up to 99% compared to
      PCL pure). Bilayers consisting of PCL and starch containing 5% PCL, with
      potassium sorbate at the interface, showed the best mechanical and barrier
      properties and interfacial adhesion while having active properties, associated
      with the antimicrobial action of potassium sorbate. 

PMID- 25965486
TI  - Improving the physical properties of starch using a new kind of water dispersible
      nano-hybrid reinforcement.
AB  - Plasticized cassava starch matrix composites reinforced by a multi-wall carbon
      nanotube (MWCNT)-hercynite (FeAl2O4) nanomaterial were developed. The hybrid
      nanomaterial consists of FeAl2O4 nanoparticles anchored strongly to the surface
      of the MWCNT. This nano-hybrid filler shows an irregular geometry, which provides
      a strong mechanical interlocking with the matrix, and excellent stability in
      water, ensuring a good dispersion in the starch matrix. The composite containing
      0.04wt.% of the nano-hybrid filler displays increments of 370% in the Young's
      modulus, 138% in tensile strength and 350% in tensile toughness and a 70%
      decrease in water vapor permeability relative to the matrix material. All of
      these significant improvements are explained in terms of the nano-hybrid filler
      homogenous dispersion and its high affinity with both plasticizers, glycerol and
      water, which induces crystallization without deterioration of the tensile
      toughness. 

PMID- 25965487
TI  - Formulation and process optimization of naproxen nanosuspensions stabilized by
      hydroxy propyl methyl cellulose.
AB  - In present study precipitation-ultrasonication was used to obtain nanosuspensions
      of poorly water-soluble drug, naproxen (NPX). We investigated the effects of HPMC
      concentration (X1) and time of ultrasonication (X2) on imperative attributes like
      mean particle size (Y1), % drug content (Y2), and time required to 90% drug
      release (Y3) via 3(2) factorial design. The morphology of nanosuspensions was
      found almost spherical by SEM observation. DSC and XRD studies suggested slight
      crystalline change in drug. FT-IR revealed lack of significant interactions
      between NPX and HPMC. Nanosuspensions of mean particle size 530.55 nm was
      achieved. Dissolution rate obtained from all nanosuspensions were markedly higher
      than pure NPX. Response surface methodology and optimized polynomial equations
      were used to select optimal formulation i.e. 1.36%W/V of X1 and 13.9 min of X2 to
      get desired response Y1; 727.97 nm, Y2; 95.59% and Y3; 8.67 min that were in
      reasonable agreement with observed value.

PMID- 25965488
TI  - Chitosan-isoniazid conjugates: Synthesis, evaluation of tuberculostatic activity,
      biodegradability and toxicity.
AB  - Novel water-soluble chitosan-isoniazid conjugates were synthesized by two
      methods: (1) the carbodiimide method using isoniazid (INH) and N-(2
      carboxyethyl)chitosan (CEC), and (2) the reaction between INH and N-(3-chloro-2
      hydroxypropyl)chitosan (CHPC). The solubility of the conjugates under
      physiological conditions was enhanced by phosphorylation. Method (1) is
      preferable in terms of obtaining conjugates with a high content of active
      substance; depending on reaction conditions, the degree of substitution in the
      INH-CEC conjugates varies from 0.08 to 0.39. Ultrasound treatment increased the
      reaction rate by a factor of 1.3-1.5, but caused partial degradation of the
      polymer. Consecutive modification led to a considerable decrease in polymer
      biodegradability in the following order: chitosan>CEC or CHPC>conjugate. In vitro
      screening of the antimicrobial activity against Mycobacterium tuberculosis H37Rv
      demonstrated a comparable or slightly higher minimum inhibitory concentration for
      conjugates than for INH itself (0.20, 0.25, and 1.05 MUg INH/mL for INH, CEC-INH,
      and CHPC-INH, respectively). A slug mucosal irritation test employing Limax
      flavus revealed a lower toxicity for the conjugates than for INH by a factor of 3
      4; the most noticeable toxicity decrease was observed for the conjugates obtained
      by method (1). Studies of acute toxicity in mice revealed a 3-4-fold increase in
      median lethal dose for the conjugates compared with INH (LD50 210, 850, and 650
      mg INH/kg for INH, CEC-INH, and CHPC-INH, respectively).

PMID- 25965489
TI  - Experimental and theoretical study of carbohydrate-ionic liquid interactions.
AB  - With increasing interest in the use of lignocellulosic biomass for the production
      of renewable transportation fuels, new approaches for biomass pretreatment have
      been of considerable interest. The conversion of biomass cellulose to water
      soluble sugars is currently one of the most intensive demands worldwide. The use
      of ionic liquids has been described as a new potentially viable development in
      this area. Indeed, previous work indicates that carbohydrates are soluble in some
      imidazolium based ionic liquids. For a better understanding of the behavior of
      such systems, theoretical quantum chemical calculation have become
      complementarities of experimental measurements. The goal of this work is to
      investigate the fundamental natures of the interaction between glucose or
      cellulose and imidazolium based ionic liquids using ab initio calculations and
      comparing these results with experimental data. Furthermore, a characterization
      study was made to investigate the changes in the cellulose structure during the
      process of solubility and regeneration with ionic liquids. 

PMID- 25965490
TI  - The mechanism of improved pullulan production by nitrogen limitation in batch
      culture of Aureobasidium pullulans.
AB  - Batch culture of Aureobasidium pullulans CCTCC M 2012259 for pullulan production
      at different concentrations of ammonium sulfate and yeast extract was
      investigated. Increased pullulan production was obtained under nitrogen-limiting
      conditions, as compared to that without nitrogen limitation. The mechanism of
      nitrogen limitation favoring to pullulan overproduction was revealed by
      determining the activity as well as gene expression of key enzymes, and energy
      supply for pullulan biosynthesis. Results indicated that nitrogen limitation
      increased the activities of alpha-phosphoglucose mutase and glucosyltransferase,
      up-regulated the transcriptional levels of pgm1 and fks genes, and supplied more
      ATP intracellularly, which were propitious to further pullulan biosynthesis. The
      economic analysis of batch pullulan production indicated that nitrogen limitation
      could reduce more than one third of the cost of raw materials when glucose was
      supplemented to a total concentration of 70 g/L. This study also helps to
      understand the mechanism of other polysaccharide overproduction by nitrogen
      limitation.

PMID- 25965491
TI  - Conductive polypyrrole/viscose fiber composites.
AB  - Polypyrrole (PPy) was polymerized with pyrrole (Py) as the monomer, FeCl3 as an
      oxidant and sodium dodecyl benzene sulfonate (SDBS) as the dopant on the surface
      of viscose fiber (VCF) to prepare the conductive PPy/VCF composites. Fourier
      transform infrared spectra (FT-IR), thermal gravimetric analysis (TGA) and X-ray
      photoelectron spectroscope (XPS) proved that the interaction between PPy and VCF
      formed in the PPy/VCF composites. Three structures of N atoms (imine, amine and
      cationic atoms) were found in PPy of PPy/VCF composites. The influence of
      reaction conditions including reaction time, Py concentration, FeCl3
      concentration and SDBS concentration on the morphology and the conductivity of
      PPy/VCF composites was investigated in detail. The orthogonal experiments were
      designed to determine the optimal reaction conditions: reaction time 5h, Py
      concentration 0.1 mol/L and FeCl3 concentration 0.25 mol/L. When PPy/VCF
      composite was washed 50 times in water, the conductivity still kept at 1.5S/cm,
      and this value was stable for more washing.

PMID- 25965492
TI  - Chitosan-Montmorillonite microspheres: A sustainable fertilizer delivery system.
AB  - Controlled release fertilizers are efficient tools that increase the
      sustainability of agricultural practices. However, the biodegradability of the
      matrices and the determination of the release into soil still require some
      investigation. This paper describes the preparation of potassium-containing
      microspheres based on chitosan and montmorillonite clay and the in situ soil
      release. The chitosan-montmorillonite microspheres were prepared using a
      coagulation method and different proportions of montmorillonite. The structural,
      thermal and morphological properties as well the water swelling and fertilizer
      sorption capacity were evaluated. The best formulations were applied in soil, and
      the fertilizer release was monitored using time-domain reflectometry (TDR).
      Montmorillonite clay provides better sorption properties than the chitosan
      microspheres because of the rough and porous surface. Due to these properties,
      high levels of fertilizer were sorbed onto the material. ChMMT33-containing
      potassium shows two specific periods of fertilizer release: the first one lasted
      approximately three days and was assigned to the external fertilizer on the
      microspheres. The second was assigned to the internal fertilizer. TDR is an
      important and fast tool and was used to determine the fertilizer release and the
      ion movement in the soil. 

PMID- 25965493
TI  - Characterization of polysaccharides extracted from spent coffee grounds by alkali
      pretreatment.
AB  - Spent coffee grounds (SCG), obtained during the processing of coffee powder with
      hot water to make soluble coffee, are the main coffee industry residues and
      retain approximately seventy percent of the polysaccharides present in the
      roasted coffee beans. The purpose of this study was to extract polysaccharides
      from SCG by using an alkali pretreatment with sodium hydroxide at 25 degrees C,
      and determine the chemical composition, as well as the antioxidant and
      antimicrobial properties of the extracted polysaccharides. Galactose (60.27%mol)
      was the dominant sugar in the recovered polysaccharides, followed by arabinose
      (19.93%mol), glucose (15.37%mol) and mannose (4.43%mol). SCG polysaccharides were
      thermostable, and presented a typical carbohydrate pattern. Additionally, they
      showed good antioxidant activity through different methods and presented high
      antimicrobial percent inhibition against Phoma violacea and Cladosporium
      cladosporioides (41.27% and 54.60%, respectively). These findings allow
      identifying possible applications for these polysaccharides in the food industry.

PMID- 25965494
TI  - The role of surfactants on ethylcellulose oleogel structure and mechanical
      properties.
AB  - The effects of surfactant addition to ethyl-cellulose (EC) based oleogels were
      examined with respect to the chemical nature of the "head" and "tail" groups of
      the surfactant. Unique sigmoidal temperature dependent rheological behavior was
      observed upon surfactant addition, suggesting additional organized structure
      formation. Glycerol-based surfactant addition lead to greatest decrease in the
      sol-gel and gel-sol transition temperatures compared to sorbitan-based
      surfactants. This behavior can be attributed to the plasticizing nature of the
      small head group of glycerol compared to the larger head group of sorbitan
      surfactants. A significant increase in the penetration force of the gels was
      observed upon surfactant addition, suggesting possible surfactant-polymer
      interactions which stiffen the polymer network. Thermal analysis detected a
      reduction in both SMS and GMS crystallization peak temperature and enthalpy. In
      the case of GMS, two melting peaks were observed upon EC addition to the oil
      phase, suggesting EC/surfactant interactions. These results demonstrate the
      effects of surfactant head group structure on EC oleogel rheological properties. 

PMID- 25965495
TI  - Thermal degradation of xylan-based hemicellulose under oxidative atmosphere.
AB  - Xylan-based hemicellulose sample is tested in TG-MS under He, 7% O2, 20% O2 and
      60% O2, in order to underpin the understanding of thermo-degradation mechanism of
      hemicellulose and biomass. The mass loss history recorded by TG can be divided
      into two main stages: (1) low-temperature stage with the peak located at around
      265 degrees C associated with thermal cracking of hemicellulose, and (2) high
      temperature stage with the peak enhanced and shifted to lower temperatures by
      oxygen concentration ascribed to char combustion. A number of prominently evolved
      ions identified by MS can be designated to acetone, acetic acid, furfural, water,
      CO, CO2 and so on. The releasing profile of smaller fragments (water, CO and CO2)
      follows the pattern of DTG curve under different oxygen concentrations
      (especially for that in the high temperature stage). A three-step consecutive
      kinetic model employing "n-order reaction function" is proposed and achieved good
      fit for the experimental mass loss data of thermo-oxidation of hemicellulose. 

PMID- 25965496
TI  - Characterization of arabinogalactan-rich mucilage from Cereus triangularis
      cladodes.
AB  - Cereus triangularis (Cactaceae) is a cactus used in food decoction as a
      traditional medicine in the North region of Madagascar to reduce stomach ache and
      intestinal diseases. Hydrocolloids were sequentially extracted from its cladodes
      with a yield of 24% (240 mg/g based on dried cladodes powder). Structural
      analyses has revealed that this polysaccharide with a molecular mass of
      8430,000g/mol was mainly composed of a galactan backbone of a (1 -> 4) linked
      beta-d-Galp residues probably substituted at position 3 by L-arabinofuranosyl
      residues. In vitro antioxidant activity of this arabinogalactan-rich fraction was
      detected and quantified by radical DPPH scavenging, hydroxyl radical scavenging,
      radical anion superoxide scavenging and reducing power method.

PMID- 25965497
TI  - Preparation and characterization of transparent PMMA-cellulose-based
      nanocomposites.
AB  - Nanocomposites of polymethylmethacrylate (PMMA) and cellulose were made by a
      solution casting method using acetone as the solvent. The nanofiber networks were
      prepared using three different types of cellulose nanofibers: (i) nanofibrillated
      cellulose (NFC), (ii) cellulose nanocrystals (CNC) and (iii) bacterial cellulose
      from nata de coca (NDC). The loading of cellulose nanofibrils in the PMMA varied
      between 0.25 and 0.5 wt%. The mechanical properties of the composites were
      evaluated using a dynamic mechanical thermal analyzer (DMTA). The flexural
      modulus of the nanocomposites reinforced with NDC at the 0.5 wt% loading level
      increased 23% compared to that of pure PMMA. The NFC composite also exhibited a
      slightly increased flexural strength around 60 MPa while PMMA had a flexural
      strength of 57 MPa. The addition of NDC increased the storage modulus (11%)
      compared to neat PMMA at room temperature while the storage modulus of PPMA/CNC
      nanocomposite containing 0.25 and 0.5 wt% cellulose increased about 46% and 260%
      to that of the pure PMMA at the glass transition temperature, respectively.
      Thermogravimetric analysis (TGA) indicated that there was no significant change
      in thermal stability of the composites. The UV-vis transmittance of the CNF
      nanocomposites decreased by 9% and 27% with the addition of 0.25 wt% CNC and NDC,
      respectively. This work is intended to spur research and development activity for
      application of CNF reinforced PMMA nanocomposites in applications such as:
      packaging, flexible screens, optically transparent films and light-weight
      transparent materials for ballistic protection.

PMID- 25965498
TI  - Carboxymethylation of (1 -> 6)-beta-glucan (lasiodiplodan): Preparation,
      characterization and antioxidant evaluation.
AB  - D-Glucans possess immunomodulatory activities and potential for the development
      of new therapeutic agents. Biological activities can be enhanced in these
      biopolymers through chemical derivatization, e.g., carboxymethylation. This work
      presents the carboxymethylation, characterization and the evaluation of
      antioxidant activities of the exocellular (1 -> 6)-beta-D-glucan produced by
      Lasiodiplodia theobromae MMPI. Thermal analysis indicated that the native and
      carboxymethylated polysaccharides presented four stages of mass-loss. The first
      stage occurred at 125 degrees C (loss of water) with two consecutive events of
      mass loss (200-400 degrees C) attributed to polymer degradation and the fourth
      stage between 425 and 620 degrees C (final decomposition). Scanning electron
      microscopy analysis indicated that the gross morphological features of
      lasiodiplodan were ruptured following carboxymethylation. X-ray diffractometry
      analysis demonstrated that the native and carboxymethylated polysaccharides
      presented a non-crystalline structure. Carboxymethylation contributed to
      improving the polysaccharide's water solubility and antioxidant capacity.

PMID- 25965499
TI  - Effect of depth beating on the fiber properties and enzymatic saccharification
      efficiency of softwood kraft pulp.
AB  - Commercial bleached softwood kraft pulp was mechanically fibrillated by a PFI
      mill with beating revolution from 5000 to 30,000 r. The extent of fibrillating on
      the pulp was evaluated by beating degree, fiber morphological properties (fiber
      length, width, coarseness and curls index), water retention value (WRV) and
      physical properties of paper made from the pulp. Depth beating process
      significantly affected the pulp fibrillations as showed by the decreased fiber
      length and width as well as the SEM analysis, but the effects were limited after
      beating revolution of 15,000. Depth beating process also improved the total
      internal pore and inter-fibril surface areas as shown by the increased WRV
      values. Substrate enzymatic digestibility (SED) of beaten pulp at 5000
      revolutions could reach 95% at cellulase loading of 15 FPU/g of glucan. After the
      enzymatic hydrolysis, the size of the pulp residues was reduced to micro-scale,
      and a relative uniform size distribution of the residues appeared at 10,000 r
      beating revolution.

PMID- 25965500
TI  - Synthesis of guanidinylated chitosan with the aid of multiple protecting groups
      and investigation of antibacterial activity.
AB  - A new synthetic approach employing two types of protecting groups,
      tertiarybutyldimethylsilyl (TBDMS) and tertiarybutyloxycarbonyl (Boc) was
      developed to obtain a series of guanidinylated chitosan derivatives. The
      synthesis was carried out in organic solvents which allowed quantitative
      reaction, a good control on the degree of substitution, and 100% substitution of
      the chitosan amino groups. Similar derivatives carrying the trimethylammonium
      group were also synthesized as reference compounds. All the derivatives were
      characterized using (1)H and COSY NMR and IR spectroscopy. The antibacterial
      effect against clinically relevant strains of S. aureus and E. coli was found to
      increase with increase in the degree of substitution and decrease in the spacer
      length of the derivatives in both the series. An optimum activity could be
      obtained at a degree of substitution above 0.5 for most derivatives. The
      trimethylammonium derivatives showed slightly higher activity than the
      corresponding guanidinium derivatives but a similar structure-activity
      relationship was obtained. 

PMID- 25965501
TI  - Modification of xylan in alkaline treated bleached hardwood kraft pulps as
      classified by attenuated total-internal-reflection (ATR) FTIR spectroscopy.
AB  - The glucuronoxylan composition of a pulp affects the bonding between cellulosic
      fibres, and thus correlates with such network properties as tensile strength.
      Here, we demonstrate the promise of attenuated total-internal-reflection (ATR)
      FTIR spectroscopy as a rapid means for classifying the xylan contained in
      commercial bleached kraft pulps. This study draws upon samples composed of
      bleached eucalyptus kraft pulps and combinations of eucalyptus with other
      commercial bleached kraft pulps. We subject these pulp samples to systematic
      extraction by sodium hydroxide solutions with concentrations ranging from 0.5% to
      6% to build a standard sample library with varying xylan content, quantified by
      acid hydrolysis, HPLC carbohydrate separation and titration. This pulp chemistry
      of mild alkaline extraction removes up to two-thirds of the xylan. In the NaOH
      concentration regime of 0.5-4%, the infrared spectral variance reflects the
      decrease in hemicellulose concentration as well as the cellulose crystallinity. A
      residual xylan component remains resistant to base solutions of higher
      concentrations. Principal component analysis of infrared spectra distinguishes
      this residual xylan as structurally variant. Both partial least squares
      multivariate analysis and univariate analysis confined to a feature at 964 cm(-1)
      in normalized second derivative IR spectra show a very good correlation with
      xylan content quantified by HPLC.

PMID- 25965502
TI  - beta-Eliminative depolymerization of the fucosylated chondroitin sulfate and
      anticoagulant activities of resulting fragments.
AB  - Fucosylated chondroitin sulfate (FCS) from sea cucumber with complex structure
      has potent anticoagulant activity by inhibition of intrinsic tenase; however, it
      could activate factor XII and platelet. To obtain FCS' fragments with selective
      inhibition on intrinsic tenase, a method for beta-eliminative depolymerization of
      FCS was developed by treating FCS benzyl esters with alkaline in anhydrous
      solution. Our results demonstrated that the glycosidic linkages of GalNAc-beta1,
      4-GlcA were selectively cleaved and distinctive Delta(4,5) unsaturated hexuronic
      acid was formed at non-reducing end of resulting fragments, while the main
      structures were essentially stable during depolymerization. By this method, five
      depolymerized fragments (dFCSs) with various molecular sizes were prepared and
      their anticoagulant activities and activation activities of factor XII and
      platelet were compared. Overall, dFCSs with Mw 3.2-8.8 kDa reserved potent
      anticoagulant activities by inhibition of intrinsic tenase, and activation
      activities of factor XII or platelet could be diminished or eliminated.

PMID- 25965503
TI  - A coarse-grain force-field for xylan and its interaction with cellulose.
AB  - We have built a coarse-grain (CG) model describing xylan and its interaction with
      crystalline cellulose surfaces. Each xylosyl or glucosyl unit was represented by
      a single grain. Our calculations rely on force-field parameters adapted from the
      atomistic description of short xylan fragments and their adsorption on cellulose.
      This CG model was first validated for xylan chains both isolated and in the bulk
      where a good match was found with its atomistic counterpart as well as with
      experimental measurements. A similar agreement was also found when short xylan
      fragments were adsorbed on the (110) surface of crystalline cellulose. The CG
      model, which was extended to the (100) and (1-10) surfaces, revealed that the
      adsorbed xylan, which was essentially extended in the atomistic situation, could
      also adopt coiled structures, especially when laying on the hydrophobic cellulose
      surfaces. 

PMID- 25965504
TI  - Incorporation of antimicrobial peptides on functionalized cotton gauzes for
      medical applications.
AB  - A large group of low molecular weight natural compounds that exhibit
      antimicrobial activity has been isolated from animals and plants during the past
      two decades. Among them, peptides are the most widespread resulting in a new
      generation of antimicrobial agents with higher specific activity. In the present
      study we have developed a new strategy to obtain antimicrobial wound-dressings
      based on the incorporation of antimicrobial peptides into polyelectrolyte
      multilayer films built by the alternate deposition of polycation (chitosan) and
      polyanion (alginic acid sodium salt) over cotton gauzes. Energy dispersive X ray
      microanalysis technique was used to determine if antimicrobial peptides
      penetrated within the films. FTIR analysis was performed to assess the chemical
      linkages, and antimicrobial assays were performed with two strains:
      Staphylococcus aureus (Gram-positive bacterium) and Klebsiella pneumonia (Gram
      negative bacterium). Results showed that all antimicrobial peptides used in this
      work have provided a higher antimicrobial effect (in the range of 4 log-6 log
      reduction) for both microorganisms, in comparison with the controls, and are non
      cytotoxic to normal human dermal fibroblasts at the concentrations tested.

PMID- 25965505
TI  - Factors influencing prescribing of fall-risk-increasing drugs to the elderly: A
      qualitative study.
AB  - OBJECTIVE: Explore the situations in which GPs associate drug use with falls
      among their elderly patients, and the factors influencing the prescribing and
      cessation of fall-risk-increasing drugs (FRIDs). DESIGN: A qualitative study with
      13 GPs who participated in two semi-structured focus groups in Central Norway.
      Participants were encouraged to share overall thoughts on the use of FRIDs among
      elderly patients and stories related to prescribing and cessation of FRIDs in
      their own practice. RESULTS: The main finding was that GPs did not immediately
      perceive the use of FRIDs to be a prominent factor regarding falls in elderly
      patients, exceptions being when the patient presented with dizziness, reported a
      fall, or when prescribing FRIDs for the first time. It was reported as common to
      renew prescriptions without performing a drug review. Factors influencing the
      prescribing and cessation of FRIDs were categorized into GPs' clinical work
      conditions, uncertainty about outcome of changing prescriptions, patients'
      prescribing demands, and lack of patient information. CONCLUSIONS: The results
      from this study indicate that GPs need to be reminded that there is a connection
      between FRID use and falls among elderly patients of enough clinical relevance to
      remember to assess the patient's drug list and perform regular drug reviews.

PMID- 25965506
TI  - Activity of Novel Synthetic Peptides against Candida albicans.
AB  - Candida spp. are the most common causes of fungal infections worldwide. Among the
      Candida species, Candida albicans remains the predominant species that causes
      invasive candidiasis in most countries. In this study, we used two peptides, KABT
      AMP and uperin 3.6 as templates to develop novel antifungal peptides. Their
      anticandidal activity was assessed using a combination of MIC, time-killing assay
      and biofilm reduction assay. Hybrid peptides, KU2 and KU3 containing a mixed
      backbone of KABT-AMP and Uperin 3.6 demonstrated the most potent anticandidal
      activity with MIC values ranging from 8-16 mg/L. The number of Trp residues and
      the amphipathic structure of peptides probably enhanced the anticandidal activity
      of peptides. Increasing the cationicity of the uperin 3.6 analogues resulted in
      reduced MIC from the range of 64-128 mg/L to 16-64 mg/L and this was also
      correlated with the antibiofilm activity and killing kinetics of the peptides.
      Peptides showed synergistic effects when used in combination with conventional
      antifungals. Peptides demonstrated low haemolytic activity but significant
      toxicity on two normal human epithelial cell lines. This study provides us with a
      better understanding on the structure-activity relationship and the balance
      between cationicity and hydrophobicity of the peptides although the therapeutic
      application of the peptides is limited. 

PMID- 25965507
TI  - Salting-Out of Methane in the Aqueous Solutions of Urea and Glycine-Betaine.
AB  - We have studied the hydrophobic association and solvation of methane molecules in
      aqueous solutions of urea and glycine betaine (GB). We have calculated the
      potentials of mean force (PMFs) between methane molecules in water, aqueous GB,
      aqueous urea and aqueous urea-GB mixtures. The PMFs and equilibrium constants
      indicate that both urea and GB increase the hydrophobic association of methane.
      Calculation of thermodynamic parameters shows that the association of methane is
      stabilized by entropy whereas solvation is favored by enthalpy. In the case of
      the water-urea-GB mixture, both hydrophobic association and solvation are
      stabilized by entropy. From the investigation of radial distribution functions,
      running coordination numbers and excess coordination numbers, we infer that both
      urea and GB are preferentially excluded from methane surface in the mixtures of
      osmolytes and methane is preferentially solvated by water molecules in all the
      mixtures. The favorable exclusion of both urea and GB from the methane surface
      suggests that both urea and GB increase the interaction between methane
      molecules, i.e., salting-out of methane. We observe that addition of both urea
      and GB to water enhances local water structure. The calculated values of
      diffusion constants of water also suggest enhanced water-water interactions in
      the presence of urea and GB. The calculated free energies of methane in these
      mixtures show that methane is less soluble in the mixtures of urea and GB than in
      water. The data on solvation free energies support the observations obtained from
      the PMFs of methane molecules. 

PMID- 25965508
TI  - Modelling the Phenological Relationships of Questing Immature Ixodes Ricinus
      (Ixodidae) Using Temperature and NDVI Data.
AB  - All active stages of the tick Ixodes ricinus were collected monthly at two sites
      in northern Spain between the years 2000 and 2007. We used percentile
      accumulation of the active stage in the environment to evaluate simple and
      coherent correlations between accumulation of the active stages of larvae and
      nymphs and medium-resolution MODIS satellite-derived information on the climate,
      including monthly and accumulated temperature and the Normalized Difference
      Vegetation Index (NDVI). This framework is not intended to predict the actual
      abundance of ticks in the field as a measure of the hazard to humans, but to
      provide a basic structure for addressing the phenology of the tick in its
      geographic range. We demonstrated that the accumulation of larval ticks in the
      active stage is a sigmoid function of the accumulated temperature from the
      beginning of the calendar year. We also demonstrated that the accumulated
      temperature necessary to recruit nymphs from the questing larval stage is a
      function of the changes in accumulated larvae and nymphs and the accumulated
      temperature and NDVI recorded by the Aqua sensor. The low p-values obtained in
      the regressions confirmed that such recruitment can be calculated using time
      intervals to estimate, for example, the beginning of the questing period or the
      time of the year when a population peak can be expected. The comparison among
      predicted and actual accumulated temperatures between larvae and nymph
      recruitment had an averaged error of +/-20 days in one complete year. The use of
      accumulated temperature and NDVI proposed in this study opens up the re
      evaluation of reports on the phenology of the tick in Europe. This framework is
      intended to evaluate the same correlations along the tick's range and predict its
      phenological patterns in areas of pathogen transmission risk for humans. 

PMID- 25965509
TI  - The role of fructose in metabolism and cancer.
AB  - Fructose consumption has dramatically increased in the last 30 years. The
      principal form has been in the form of high-fructose corn syrup found in soft
      drinks and processed food. The effect of excessive fructose consumption on human
      health is only beginning to be understood. Fructose has been confirmed to induce
      several obesity-related complications associated with the metabolic syndrome.
      Here we present an overview of fructose metabolism and how it contrasts with that
      of glucose. In addition, we examine how excessive fructose consumption can affect
      de novo lipogenesis, insulin resistance, inflammation, and reactive oxygen
      species production. Fructose can also induce a change in the gut permeability and
      promote the release of inflammatory factors to the liver, which has potential
      implications in increasing hepatic inflammation. Moreover, fructose has been
      associated with colon, pancreas, and liver cancers, and we shall discuss the
      evidence for these observations. Taken together, data suggest that sustained
      fructose consumption should be curtailed as it is detrimental to long-term human
      health. 

PMID- 25965510
TI  - Somatotopic mismatch of hand representation following stroke: is recovery
      possible?
AB  - Well-organized somatotopic representation of the hand is required to interpret
      input from cutaneous mechanoreceptors. Previous reports have identified patients
      with various distortions of somatotopic representation after stroke. Importantly,
      those patients were investigated years after the stroke, indicating that afferent
      signal regained access to the cortical circuits; however, further plastic
      changes, which would re-establish somatotopic order and ability to correctly
      localize tactile stimuli, did not follow. Thus, it was not known whether
      somatotopic organization could be restored in such patients and whether there is
      a potential for new rehabilitation strategies. This is the first case report
      demonstrating normalization of somatotopic representation. 

PMID- 25965511
TI  - Portuguese tin-glazed earthenware from the 17th century. Part 2: A spectroscopic
      characterization of pigments, glazes and pastes of the three main production
      centers.
AB  - Sherds representative of the three Portuguese faience production centers of the
      17th century - Lisbon, Coimbra and Vila Nova were studied with the use of mostly
      non-invasive spectroscopies, namely: ground state diffuse reflectance absorption
      (GSDR), micro-Raman, Fourier-transform infrared (FT-IR) and proton induced X-ray
      (PIXE) or X-ray fluorescence emission (XRF). X-ray diffraction (XRD) experiments
      were also performed. The obtained results evidence a clear similarity in the
      pastes of the pottery produced Vila Nova and some of the ceramic pastes from
      Lisbon, in accordance with documental sources that described the use of Lisbon
      clays by Vila Nova potters, at least since mid 17th century. Quartz and Gehlenite
      are the main components of the Lisbon's pastes, but differences between the
      ceramic pastes were detected pointing out to the use of several clay sources. The
      spectroscopic trend exhibited Coimbra's pottery is remarkably different, Quartz
      and Diopside being the major components of these pastes, enabling one to well
      define a pattern for these ceramic bodies. The blue pigment from the Lisbon
      samples is a cobalt oxide that exists in the silicate glassy matrix, which
      enables the formation of detectable cobalt silicate microcrystals in most
      productions of the second half of the 17th century. No micro-Raman cobalt blue
      signature could be detected in the Vila Nova and Coimbra blue glazes. This is in
      accordance with the lower kiln temperatures in these two production centers and
      with Co(2+) ions dispersed in the silicate matrix. In all cases the white glaze
      is obtained with the use of tin oxide. Hausmannite was detected as the manganese
      oxide mineral used to produce the purple glaze (wine color "vinoso") in Lisbon. 

PMID- 25965512
TI  - Insights into the new Th (IV) sulfate fluoride complex: Synthesis, crystal
      structures, and temperature dependent spectroscopic properties.
AB  - Under hydrothermal condition, the decomposition of methanesulfonic acid to
      sulfate anion is observed, resulting in the formation of a novel thorium sulfate
      fluoride compound ThF2(SO4)(H2O) (1). This complex is structurally characterized
      by single crystal X-ray diffraction, revealing a three-dimensional structure
      crystallized in the monoclinic space-group P21/n, where thorium cation is nine
      coordinated by four SO4(2-) oxygen atoms, four bridging F(-), and one H2O
      molecule. The crystal lattice parameters are a=6.9065(7) A, b=6.9256(7) A,
      c=10.5892(11) A, beta=96.755(2) degrees , V=502.98(9) A(3), Z=4. The temperature
      dependent UV-Vis-NIR absorption spectra and fluorescence spectra were collected
      from 77K to 300 K, where the intensities of the peaks varied as a function of
      temperature. The Raman vibrational spectrum of the samples collected from 100 to
      2000 cm(-1) shows identical SO4(2-) vibration modes.

PMID- 25965514
TI  - Cathodoluminescence properties of gadolinium-doped CaMoO4:Eu nanoparticles.
AB  - Gadolinium (Gd(3+)) doped CaMoO4:Eu nanoparticles were prepared via facile auto
      combustion route and annealed at 900  degrees C for ~4 h. X-ray diffraction study
      confirms the tetragonal scheelite type of CaMoO4 phase. Low voltage
      cathodoluminescent (CL) measurement were performed for Gd(3+) (0 and 10 at.%) co
      doped CaMoO4:Eu as a function of accelerating voltage and filament current. CL
      studies confirm that Gd(3+) co-doped CaMoO4:Eu has a visible emission peak
      centered at ~615 nm and a broad host emission band in the range 380-550 nm.
      Commission Internationale de L'Eclairage chromaticity diagram co-ordinates of
      Gd(3+) co-doped CaMoO4:Eu are found to be in reddish orange region as was
      observed through photoluminescence and CL spectra.

PMID- 25965513
TI  - Vibrational spectroscopy, ab initio calculations and Frontier Orbital analysis of
      4,5,6,8,9-pentachloropyrimido-[1,2-a][1,8]naphthyridin-10-one.
AB  - In this work we present a study of the vibrational spectra of 4,5,6,8,9
      pentachloropyrimido-[1,2-a][1,8]naphthyridin-10-one, C11H2Cl5N3O, a substance
      belonging to the important pharmacological class of 1,8-naphthyridine
      derivatives. The Fourier transform infrared and the Fourier transform Raman
      spectra of the crystal were recorded at room temperature in the regions 400-4000
      and 50-4000 cm(-1), respectively. Vibrational wavenumbers were predicted using
      Density Functional Theory calculations with the B3LYP functional on 6-31G(d,p)
      and 6-311++G(d,p) basis sets. The descriptions of the normal modes were made
      after calculating the potential energy distribution. Additionally, potential
      reaction sites were evaluated through Mulliken population and Frontier Orbital
      analysis.

PMID- 25965515
TI  - Raman spectroscopic study of phosphogypsum thermal reduction with the
      carbonaceous material.
AB  - Elemental sulphur (S) can be produced from hydrogen sulphide (H2S) in a PiPco or
      Iron process. In turn H2S can be stripped with carbon dioxide (CO2) from calcium
      sulphide (CaS) obtained from the thermal reduction of phosphogypsum with carbon.
      The reaction pathway for the thermal reduction of the phosphogypsum with graphite
      was studied using thermogravimetric analysis and in situ Raman spectroscopy. The
      dehydration of the phosphogypsum to anhydrite was completed at about 142  degrees
      C. The dehydration was followed by the formation of the intermediate compound at
      about 860  degrees C which is characterised by a mass loss of about 11%. The
      intermediate compound, identified using the in situ Raman spectroscopy to be a
      dehydrated orschallite-type compound (Ca3[SO4][SO3]2), converted to CaS at about
      935  degrees C. The presence of the metal impurities in the phosphogypsum:
      Ni(2+)(4 mg kg(-1)); Co(2+)(2 mg kg(-1)); Mn(2+)(5 mg kg(-1)); Cu(2+)(14 mg kg(
      1)); Fe(2+)(200 mg kg(-1)) and Mg(2+)(300 mg kg(-1)) showed no influence the
      onset temperature for the reduction reaction.

PMID- 25965516
TI  - Study of chemical bonding, physical and biological effect of metformin drug as an
      organized medicine for diabetes patients with chromium(III) and vanadium(IV)
      ions.
AB  - New vanadium(IV) and chromium(III) complexes of metformin (MFN) were synthesized
      upon the chemical interaction between vanadyl(II) sulfate monohydrate or
      chromium(III) chloride hexahydrate with metformin diabetic drug in the media of a
      pure grade of methanol solvent. The [(VO)2(MFN)2(SO4)2]2H2O and
      [Cr(MFN)3].Cl3.6H2O complexes were discussed using microanalytical measurements,
      molar conductance, spectroscopic (infrared, ESR, XRD, and UV-vis), effective
      magnetic moment, scanning electron microscopy (SEM), and thermal analyses
      (TG/DTG). The elemental analysis shows that VO(II) and Cr(III) complexes were
      associated with 1:1 and 1:3M ratios, respectively. The infrared spectroscopic
      results data received from the comparison between free MFN free ligand and their
      vanadyl(II) and chromium(III) complexes were proven that metformin reacted with
      respected metal ions as a bidentate ligand through its two imino groups. The
      kinetic thermodynamic parameters were estimated from the DTG curves. The
      microstructure changes of the VO(II) and Cr(III) complexes have been probed using
      positron annihilation lifetime (PAL) and positron annihilation Doppler broadening
      (PADB) techniques. The PAL and PADB line-shape parameters were found to be
      dependent on the structure, electronic configuration and molecular weight of
      metal complexes. Antimicrobial activity of the metformin free ligand and its
      vanadyl(II) and chromium(III) complexes were evaluated against the gram negative
      and gram positive bacteria strains and different fungal strains. Moderate
      antimicrobial activity recorded by disk diffusion inhibition growth zone method
      in vanadyl(II) and chromium(III) complexes compared to metformin free ligand. 

PMID- 25965517
TI  - Scanning electron microscopy with energy dispersive spectroscopy and Raman and
      infrared spectroscopic study of tilleyite Ca5Si2O7(CO3)(2-)Y.
AB  - The mineral tilleyite-Y, a carbonate-silicate of calcium, has been studied by
      scanning electron microscopy with chemical analysis using energy dispersive
      spectroscopy (EDX) and Raman and infrared spectroscopy. Multiple carbonate
      stretching modes are observed and support the concept of non-equivalent carbonate
      units in the tilleyite structure. Multiple Raman and infrared bands in the OH
      stretching region are observed, proving the existence of water in different
      molecular environments in the structure of tilleyite. Vibrational spectroscopy
      offers new information on the mineral tilleyite. 

PMID- 25965518
TI  - Optical properties of Lead bismuth borate glasses doped with neodymium oxide.
AB  - Neodymium doped Lead bismuth borate glasses with the composition of 25PbO-25Bi2O3
      50B2O3:xNd2O3, where x=0.5, 1, 1.5 and 2 mol%, have been prepared by melt
      quenching technique. The behavior of the density and molar volume allows
      concluding that, addition of Nd2O3 leads to the formation of non-bridging oxygen.
      Rare earth ion parameters have been calculated and studied. The optical band gap
      (Eg), and band tails (Ee) were determined. Judd-Ofelt theory for the intensity
      analysis of induced electric dipole transitions has been applied to the measured
      oscillator strengths of the absorption bands to determine the three
      phenomenological intensity parameters Omega2, Omega4 and Omega6 for glass. It was
      observed that the deviation parameters, rms, was found to be 0.56:0.58(*10(-6)).
      The estimated Judd-Ofelt parameters were found to be Nd2O3concentration
      dependent. The hypersensitive transition, (4)I9/2->(4)G5/2+(2)G7/2, is closely
      related to Omega2 parameter.

PMID- 25965519
TI  - Vibrational spectra, HOMO, LUMO, MESP surfaces and reactivity descriptors of
      amylamine and its isomers: A DFT study.
AB  - Amylamine constitutes an important class of organic compounds which exists in a
      variety of ammonia derivatives. In present study, a comparative analysis of
      amylamine and its two potential isomers, iso-amylamine and tert-amylamine, has
      been performed using density functional theory with B3LYP method and 6-311G(d,p)
      as the basis set. The equilibrium structures of amylamine as well as its iso and
      tert forms have been obtained. The vibrational spectroscopic analysis has been
      carried out for the three molecules and complete assignments to all possible
      modes have been offered. The HOMO, LUMO and MESP surfaces are analyzed to discuss
      the chemical reactivity patterns in the molecules. A number of reactivity
      parameters have been calculated to further explain their chemical reactivity. The
      thermodynamic and nonlinear optical parameters are also calculated and discussed.

PMID- 25965520
TI  - Synthesis of two new silver(I) complexes with 3-bromoquinoline: Molecular
      structure, spectroscopic characterizations and DFT studies.
AB  - Two new Ag(+) complexes with 3-bromoquinoline (3BrQ) have been synthesized and
      characterized using elemental analysis, FTIR, NMR and mass spectra. The studied
      complexes have the formula [Ag(3BrQ)(OAC)]; 1 and [Ag(3BrQ)3(TCA)]; 2 where OAC
      and TCA are acetate and trichloroacetate, respectively. Based on the DFT
      calculations, 1 and 2 showed distorted trigonal planar and distorted tetrahedral
      coordination geometry. The electronic properties such as dipole moment (MU),
      polarizability (alpha0), HOMO and LUMO energies are calculated using the same
      level of theory. These electronic parameters were used to predict the nonlinear
      optical properties of the studied compounds. The studied silver complexes were
      predicted to be better nonlinear optical materials than urea. The electronic
      spectra of these complexes are calculated using the TD-DFT calculations. The
      infrared vibrational spectra were assigned based on the potential energy
      distribution (PED) analysis. The calculated (1)H NMR chemical shift values using
      GIAO approach showed good agreement with the experimental data. The
      intramolecular charge transfer interactions of the title molecules were studied
      by natural bond orbital (NBO) analysis. 

PMID- 25965521
TI  - Ku stabilizes replication forks in the absence of Brc1.
AB  - DNA replication errors are a major source of genome instability in all organisms.
      In the fission yeast Schizosaccharomyces pombe, the DNA damage response protein
      Brc1 binds phospho-histone H2A (gammaH2A)-marked chromatin during S-phase, but
      how Brc1 protects genome integrity remains unclear. Here we report that the non
      homologous end-joining (NHEJ) protein Ku becomes critical for survival of
      replication stress in brc1? cells. Ku's protective activity in brc1? cells does
      not involve its canonical NHEJ function or its roles in protecting telomeres or
      shielding DNA ends from Exo1 exonuclease. In brc1? pku80? cells, nuclear foci of
      Rad52 homologous recombination (HR) protein increase and Mus81-Eme1 Holliday
      junction resolvase becomes critical, indicating increased replication fork
      instability. Ku's localization at a ribosomal DNA replication fork barrier
      associated with frequent replisome-transcriptosome collisions increases in brc1?
      cells and increased collisions correlate with an enhanced requirement for Brc1.
      These data indicate that Ku stabilizes replication forks in the absence of Brc1. 

PMID- 25965522
TI  - Organocatalytic enantioselective peroxidation of ketimines derived from isatins.
AB  - The first catalytic enantioselective addition of hydroperoxides to ketimines
      derived from isatins has been developed. Excellent yields and
      enantioselectivities were observed for the reaction of various ketimines with
      peroxides using a cinchona alkaloid sulfonamide catalyst. Both enantiomers of
      products could be obtained by using pseudoenantiomeric chiral catalysts. The
      obtained product can be converted to optically active alpha-amino hydroperoxide. 

PMID- 25965524
TI  - The SPP and training in pulmonology.

PMID- 25965523
TI  - Human Haploid Cell Genetics Reveals Roles for Lipid Metabolism Genes in
      Nonapoptotic Cell Death.
AB  - Little is known about the regulation of nonapoptotic cell death. Using massive
      insertional mutagenesis of haploid KBM7 cells we identified nine genes involved
      in small-molecule-induced nonapoptotic cell death, including mediators of fatty
      acid metabolism (ACSL4) and lipid remodeling (LPCAT3) in ferroptosis. One novel
      compound, CIL56, triggered cell death dependent upon the rate-limiting de novo
      lipid synthetic enzyme ACC1. These results provide insight into the genetic
      regulation of cell death and highlight the central role of lipid metabolism in
      nonapoptotic cell death.

PMID- 25965525
TI  - Usefulness of consecutive C-reactive protein measurements in follow-up of severe
      community-acquired pneumonia.

PMID- 25965526
TI  - Increased survival with mechanical ventilation in posttuberculosis patients with
      combination of respiratory failure and chest wall deformity.

PMID- 25965527
TI  - Comparison of the yield of transthoracic needle aspiration and core biopsy
      between pulmonologist and radiologist in a community practice.

PMID- 25965528
TI  - A 4-year trial of tiotropium in chronic obstructive pulmonary disease (UPLIFT
      trial).

PMID- 25965529
TI  - Obesity Does Not Influence Outcomes in Hepatocellular Carcinoma Patients
      following Curative Hepatectomy.
AB  - BACKGROUND: Whether obesity affects surgical outcomes in patients with
      hepatocellular carcinoma (HCC) is controversial. Here we retrospectively
      evaluated the impact of obesity on outcomes in HCC patients after curative
      hepatectomy. METHODS: Patients with Child-Pugh A liver function who underwent
      curative hepatectomy between 2006 and 2010 were categorized as obese (BMI >=25
      kg/m2, n = 68) and non-obese (<25 kg/m2, n = 242). To reduce interference from
      baseline differences between the two groups, propensity score-matched analysis
      was performed in the ratio 1:2 using a caliper width of 0.1. Surgical outcomes
      were compared for 61 obese and 115 non-obese patients. RESULTS: Obese patients
      had higher levels of albumin and aspartate aminotransferase, and more solitary
      tumors compared to the non-obese patients (all P<0.05). In the propensity-matched
      cohort, baseline characteristics did not differ between the two groups (all
      P>0.05). Obese and non-obese patients had comparable 30-day mortality (1.6% vs.
      2.6%, P = 1.000), 90-day mortality (3.3% vs. 4.3%, P = 1.000), and incidence of
      postoperative complications (19.7% vs. 18.3%, P = 0.819). Overall survival at 1,
      3, and 5 years was similar for obese patients (83.6%, 63.6%, 41.6%) as for non
      obese patients (80.9%, 65.9%, 49.1%; P = 0.358). Disease-free survival at 1, 3,
      and 5 years was also similar for obese patients (71.5%, 36.3%, 24.3%) as for non
      obese ones (60.2%, 43.7%, 27.7%; P = 0.969). CONCLUSION: Our propensity score
      matched analysis strengthens the case that obesity does not adversely affect
      surgical outcomes of HCC patients undergoing curative hepatectomy.

PMID- 25965530
TI  - Challenges for the portuguese journal of pulmonology.

PMID- 25965531
TI  - The Influence of an undergraduate scientific initiation programme onn the
      professional profile of new physicians.
AB  - INTRODUCTION: This paper studies the influence of a Scientific Initiation
      Programme (SIP) on the professional profile of new doctors from a Brazilian
      university. AIM AND METHODS: Evaluate fifty-two new doctors divided into two
      groups matched by sex, age and academic performance and differing only in
      participation in the SIP. Professional and socioeconomic data were collected,
      including schooling of parents; average income before, during and after the
      medical course; current professional situation; results of exams for civil
      servant recruitment; and titles and degrees obtained after graduation. RESULTS:
      Significant differences were found only in civil servant recruitment exam results
      (p=0.0098) and in income after graduation (p=0.02), which were both higher in the
      non-SIP group. Only one doctor got a M.Sc. degree after graduation, but many of
      them in both groups obtained technical titles, and had papers presented at
      congresses or published. CONCLUSIONS: Apparently, taking part in a SIP led to
      lower income and worse civil servant recruitment exam results. However, this may
      only reflect a transient phase in a long-term process. New research currently
      under way will answer this remaining question, now that more time has elapsed
      since graduation. Rev Port Pneumol 2010; XVI (5): 797-808.

PMID- 25965532
TI  - Labeling strategy and signal broadening mechanism of Protein NMR spectroscopy in
      Xenopus laevis oocytes.
AB  - We used Xenopus laevis oocytes, a paradigm for a variety of biological studies,
      as a eukaryotic model system for in-cell protein NMR spectroscopy. The small
      globular protein GB1 was one of the first studied in Xenopus oocytes, but there
      have been few reports since then of high-resolution spectra in oocytes. The
      scarcity of data is at least partly due to the lack of good labeling strategies
      and the paucity of information on resonance broadening mechanisms. Here, we
      systematically evaluate isotope enrichment and labeling methods in oocytes
      injected with five different proteins with molecular masses of 6 to 54 kDa. (19)
      F labeling is more promising than (15) N, (13) C, and (2) H enrichment. We also
      used (19) F NMR spectroscopy to quantify the contribution of viscosity, weak
      interactions, and sample inhomogeneity to resonance broadening in cells. We found
      that the viscosity in oocytes is only about 1.2 times that of water, and that
      inhomogeneous broadening is a major factor in determining line width in these
      cells. 

PMID- 25965533
TI  - Correction: Three bonding modes of bis(2-picolyl)phenylphosphine at iron:
      isolation of a dinuclear iron complex featuring dearomatized pyridine moieties.

PMID- 25965534
TI  - Human infection with an avian influenza A (H9N2) virus in the middle region of
      China.
AB  - During the epidemic period of the novel H7N9 viruses, an influenza A (H9N2) virus
      was isolated from a 7-year-old boy with influenza-like illness in Yongzhou city
      of Hunan province in November 2013. To identify the possible source of infection,
      environmental specimens collected from local live poultry markets
      epidemiologically linked to the human case in Yongzhou city were tested for
      influenza type A and its subtypes H5, H7, and H9 using real-time RT-PCR methods
      as well as virus isolation, and four other H9N2 viruses were isolated. The real
      time RT-PCR results showed that the environment was highly contaminated with
      avian influenza H9 subtype viruses (18.0%). Sequencing analyses revealed that the
      virus isolated from the patient, which was highly similar (98.5-99.8%) to one of
      isolates from environment in complete genome sequences, was of avian origin.
      Based on phylogenetic and antigenic analyses, it belonged to genotype S and Y280
      lineage. In addition, the virus exhibited high homology (95.7-99.5%) of all six
      internal gene lineages with the novel H7N9 and H10N8 viruses which caused
      epidemic and endemic in China. Meanwhile, it carried several mammalian adapted
      molecular residues including Q226L in HA protein, L13P in PB1 protein, K356R,
      S409N in PA protein, V15I in M1 protein, I28V, L55F in M2 protein, and E227K in
      NS protein. These findings reinforce the significance of continuous surveillance
      of H9N2 influenza viruses.

PMID- 25965535
TI  - Impulse Oscillometry and Bronchiectasis. We Still Haven't Found What We're
      Looking For?

PMID- 25965536
TI  - Outpatient management eligibility criteria for patients who have acute
      symptomatic pulmonary embolism.

PMID- 25965537
TI  - Evaluation of pulmonary complaints in the emergency department. Time to go back
      to the basics.

PMID- 25965538
TI  - Call the pulmonologist? The role of pulmonary specialists in the care of lung
      cancer patients with chronic obstructive pulmonary disease in a time of cost
      constraints.

PMID- 25965539
TI  - The ATS Foundation. 10 Years Old and Powered to Grow.

PMID- 25965540
TI  - Historical perspectives of bronchoscopy. Connecting the dots.
AB  - The era of bronchoscopy began with Gustav Killian in 1876 when he removed a pork
      bone from a farmer's airway, using an esophagoscope. Prompted by this
      accomplishment, Chevalier Jackson, an American otolaryngologist, laid the
      platform for the modern-day rigid bronchoscope in the early twentieth century. In
      1967 Shigeto Ikeda revolutionized the field of bronchoscopy by his innovation of
      the fiberoptic bronchoscope. Today, bronchoscopy and interventional pulmonology
      have become an integral part of pulmonary medicine and an established
      subspecialty. Numerous innovators have furthered the horizons of this technology.
      In the early 1980s Ko-Pen Wang introduced transbronchial needle aspiration to
      sample mediastinal lesions while Jean-Francois Dumon developed methods for laser
      photoresection and for placing stents thorough the bronchoscope. More recently,
      application of endobronchial ultrasound and electromagnetic navigation tools has
      further galvanized the role of bronchoscopy. The success of lung transplantation
      also belongs in part to flexible bronchoscopy. Today, researchers are looking
      into treating emphysema as well as asthma, using bronchoscopic techniques. We
      believe 2015 is a good time to look back on the history of bronchoscopy and to
      recognize its major milestones. This article attempts to connect the historical
      dots in this field of research, with the hope that our effort helps future
      generations improve the welfare of patients with lung ailments. 

PMID- 25965541
TI  - Progress in the development of volatile exhaled breath signatures of lung cancer.
AB  - RATIONALE: Volatile organic compounds present in the exhaled breath have shown
      promise as biomarkers of lung cancer. Advances in colorimetric sensor array
      technology, breath collection methods, and clinical phenotyping may lead to the
      development of a more accurate breath biomarker. OBJECTIVES: Perform a discovery
      level assessment of the accuracy of a colorimetric sensor array-based volatile
      breath biomarker. METHODS: Subjects with biopsy-confirmed untreated lung cancer,
      and others at risk for developing lung cancer, performed tidal breathing into a
      breath collection instrument designed to expose a colorimetric sensor array to
      the alveolar portion of the breath. Random forest models were built from the
      sensor output of 70% of the study subjects and were tested against the remaining
      30%. Models were developed to separate cancer and subgroups from control, and to
      characterize the cancer. Additional models were developed after matching the
      clinical phenotypes of cancer and control subjects. MEASUREMENTS AND MAIN
      RESULTS: Ninety-seven subjects with lung cancer and 182 control subjects
      participated. The accuracies, reported as C-statistics, for models of cancer and
      subgroups versus control ranged from 0.794 to 0.861. The accuracy was improved by
      developing models for cancer and control groups selected through propensity
      matching for clinical variables. A model built using only subjects from the
      largest available clinical subgroup (49 subjects) had a C-statistic of 0.982.
      Models developed and tested to characterize cancer histology, and to compare
      early- with late-stage cancer, had C-statistics of 0.881-0.960. CONCLUSIONS: The
      colorimetric sensor array signature of exhaled breath volatile organic compounds
      was capable of distinguishing patients with lung cancer from clinically relevant
      control subjects in a discovery level trial. The incorporation of clinical
      phenotypes into the further development of this biomarker may optimize its
      accuracy.

PMID- 25965542
TI  - Medical thoracoscopy unveils a hidden choroidal melanoma.

PMID- 25965543
TI  - Trends in sepsis and infection sources in the United States. A population-based
      study.

PMID- 25965544
TI  - Reply: trends in sepsis and infection sources in the United States. A population
      based study.

PMID- 25965546
TI  - Interplay of curvature and temperature in the Casimir-Polder interaction.
AB  - We study the Casimir-Polder interaction at finite temperatures between a
      polarizable small, anisotropic particle and a non-planar surface using a
      derivative expansion. We obtain the leading and the next-to-leading curvature
      corrections to the interaction for low and high temperatures. Explicit results
      are provided for the retarded limit in the presence of a perfectly conducting
      surface. 

PMID- 25965545
TI  - High Prevalence of Co-Infections by Invasive and Non-Invasive Chlamydia
      trachomatis Genotypes during the Lymphogranuloma Venereum Outbreak in Spain.
AB  - The evolution of Chlamydia trachomatis is mainly driven by recombination events.
      This fact can be fuelled by the coincidence in several European regions of the
      high prevalence of non-invasive urogenital genotypes and lymphogranuloma venereum
      (LGV) outbreaks. This scenario could modify the local epidemiology and favor the
      selection of new C. trachomatis variants. Quantifying the prevalence of co
      infection could help to predict the potential risk in the selection of new
      variants with unpredictable results in pathogenesis or transmissibility. In the
      2009-2013 period, 287 clinical samples with demonstrated presence of C.
      trachomatis were selected. They were divided in two groups. The first group was
      constituted by 137 samples with C. trachomatis of the LGV genotypes, and the
      second by the remaining 150 samples in which the presence of LGV genotypes was
      previously excluded. They were analyzed to detect the simultaneous presence of
      non-LGV genotypes based on pmpH and ompA genes. In the first group, co-infections
      were detected in 10.9% of the cases whereas in the second group the prevalence
      was 14.6%, which is the highest percentage ever described among European
      countries. Moreover, bioinformatic analyses suggested the presence among men who
      have sex with men of a pmpH-recombinant variant, similar to strains described in
      Seattle in 2002. This variant was the result of genetic exchange between
      genotypes belonging to LGV and members of G-genotype. Sequencing of other genes,
      phylogenetically related to pathotype, confirmed that the putative recombinant
      found in Madrid could have a common origin with the strains described in Seattle.
      Countries with a high prevalence of co-infections and high migration flows should
      enhance surveillance programs in at least their vulnerable population. 

PMID- 25965547
TI  - Removal of mercury (II), elemental mercury and arsenic from simulated flue gas by
      ammonium sulphide.
AB  - A tubular resistance furnace was used as a reactor to simulate mercury and
      arsenic in smelter flue gases by heating mercury and arsenic compounds. The flue
      gas containing Hg(2+), Hg(0) and As was treated with ammonium sulphide. The
      experiment was conducted to investigate the effects of varying the concentration
      of ammonium sulphide, the pH value of ammonium sulphide, the temperature of
      ammonium sulphide, the presence of SO2 and the presence of sulphite ion on
      removal efficiency. The prepared adsorption products were characterized by
      Fourier transform infrared spectroscopy, X-ray diffraction, X-ray photoelectron
      spectroscopy and scanning electron microscopy. The results showed that the
      optimal concentration of ammonium sulphide was 0.8 mol/L. The optimal pH value of
      ammonium sulphide was 10, and the optimal temperature of ammonium sulphide was 20
      degrees C.Under the optimum conditions, the removal efficiency of Hg(2+), Hg(0)
      and As could reach 99%, 88.8%, 98%, respectively. In addition, SO2 and sulphite
      ion could reduce the removal efficiency of mercury and arsenic from simulated
      flue gas. 

PMID- 25965548
TI  - Multichannel compressive sensing MRI using noiselet encoding.
AB  - The incoherence between measurement and sparsifying transform matrices and the
      restricted isometry property (RIP) of measurement matrix are two of the key
      factors in determining the performance of compressive sensing (CS). In CS-MRI,
      the randomly under-sampled Fourier matrix is used as the measurement matrix and
      the wavelet transform is usually used as sparsifying transform matrix. However,
      the incoherence between the randomly under-sampled Fourier matrix and the wavelet
      matrix is not optimal, which can deteriorate the performance of CS-MRI. Using the
      mathematical result that noiselets are maximally incoherent with wavelets, this
      paper introduces the noiselet unitary bases as the measurement matrix to improve
      the incoherence and RIP in CS-MRI. Based on an empirical RIP analysis that
      compares the multichannel noiselet and multichannel Fourier measurement matrices
      in CS-MRI, we propose a multichannel compressive sensing (MCS) framework to take
      the advantage of multichannel data acquisition used in MRI scanners. Simulations
      are presented in the MCS framework to compare the performance of noiselet
      encoding reconstructions and Fourier encoding reconstructions at different
      acceleration factors. The comparisons indicate that multichannel noiselet
      measurement matrix has better RIP than that of its Fourier counterpart, and that
      noiselet encoded MCS-MRI outperforms Fourier encoded MCS-MRI in preserving image
      resolution and can achieve higher acceleration factors. To demonstrate the
      feasibility of the proposed noiselet encoding scheme, a pulse sequences with
      tailored spatially selective RF excitation pulses was designed and implemented on
      a 3T scanner to acquire the data in the noiselet domain from a phantom and a
      human brain. The results indicate that noislet encoding preserves image
      resolution better than Fouirer encoding. 

PMID- 25965549
TI  - Does belatacept improve outcomes for kidney transplant recipients? A systematic
      review.
AB  - BACKGROUND: Belatacept was intended to provide better outcomes for kidney
      transplant (KT) recipients by allowing minimization/withdrawal of calcineurin
      inhibitors (CNI) and steroids. METHODS: We searched for randomized controlled
      trials (RCTs) in adult KT comparing belatacept with CNIs. Methodological quality
      was assessed. Meta-analyses were performed to calculate odds ratios (OR) and mean
      differences (MD). RESULTS: Six RCTs were included. Pooled analyses found no
      differences for acute rejection at any time point. Renal function [Calculated
      glomerular filtration rate (cGFR)] was better with belatacept at 12 and 24 months
      (MD = 11.7 and 13.7 ml/min/1.73 m(2) ). New onset diabetes after transplantation
      was lower with belatacept at 12 months (OR = 0.43). Systolic and diastolic blood
      pressures were lower at 12 months (MD -7.2 and -3.1 mmHg) as were triglycerides
      at 12 and 24 months (MD = -32.9 and -41.7 mg/dl). Total and low-density
      lipoprotein cholesterol were lower with belatacept at 24 months (MD = -19.8 and 
      10.6 mg/dl). There were no differences for other outcomes. CONCLUSION: Limited
      available data suggest a potential benefit for belatacept by reducing the risk of
      CNI toxicity, especially renal function, without evidence of increased acute
      rejection. There were no safety issues apart from a possible risk of post
      transplant lymphoproliferative disorder in Epstein-barr virus-seronegative
      recipients. Further studies are required to confirm this benefit.

PMID- 25965550
TI  - Progress in RNAi-mediated Molecular Therapy of Acute and Chronic Myeloid
      Leukemia.
AB  - Leukemias arise from genetic alterations in normal hematopoietic stem or
      progenitor cells, leading to impaired regulation of proliferation,
      differentiation, apoptosis, and survival of the transformed cells. With the
      advent of RNA interference (RNAi) and the short interfering RNA (siRNA) as its
      pharmacological mediator, it is becoming possible to modulate specific targets at
      will. This article summarizes current attempts to utilize RNAi reagents for
      therapy of leukemias, focusing on acute and chronic myeloid leukemia. We first
      present unique aspects of RNAi-mediated therapy, followed by a brief background
      on the delivery technology of RNAi reagents. The need for leukemia-specific
      delivery of siRNA is discussed by describing approaches that targeted agents to
      leukemic cells. Pharmacokinetics and biodistribution of RNAi agents are then
      presented, highlighting the critical issues pertinent to emerging siRNA therapy.
      Efforts to deliver specific RNAi therapies are then summarized in the context of
      expected clinical outcomes, focusing on limiting leukemic cell survival,
      sensitizing malignant cells to chemotherapy, mobilization of leukemic cells, and
      eradication of leukemic stem cells. We conclude with a perspective on the future
      of RNAi therapy, emphasizing the technological requirements and mechanistic
      challenges for clinical entry. 

PMID- 25965551
TI  - Normalization of Overexpressed alpha-Synuclein Causing Parkinson's Disease By a
      Moderate Gene Silencing With RNA Interference.
AB  - The alpha-synuclein (SNCA) gene is a responsible gene for Parkinson's disease
      (PD); and not only nucleotide variations but also overexpression of SNCA appears
      to be involved in the pathogenesis of PD. A specific inhibition against mutant
      SNCA genes carrying nucleotide variations may be feasible by a specific silencing
      such as an allele-specific RNA interference (RNAi); however, there is no method
      for restoring the SNCA overexpression to a normal level. Here, we show that an
      atypical RNAi using small interfering RNAs (siRNAs) that confer a moderate level
      of gene silencing is capable of controlling overexpressed SNCA genes to return to
      a normal level; named "expression-control RNAi" (ExCont-RNAi). ExCont-RNAi
      exhibited little or no significant off-target effects in its treated PD patient's
      fibroblasts that carry SNCA triplication. To further assess the therapeutic
      effect of ExCont-RNAi, PD-model flies that carried the human SNCA gene underwent
      an ExCont-RNAi treatment. The treated PD-flies demonstrated a significant
      improvement in their motor function. Our current findings suggested that ExCont
      RNAi might be capable of becoming a novel therapeutic procedure for PD with the
      SNCA overexpression, and that siRNAs conferring a moderate level of gene
      silencing to target genes, which have been abandoned as useless siRNAs so far,
      might be available for controlling abnormally expressed disease-causing genes
      without producing adverse effects. 

PMID- 25965552
TI  - Intraventricular Delivery of siRNA Nanoparticles to the Central Nervous System.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disease currently
      lacking effective treatment. Efficient delivery of siRNA via nanoparticles may
      emerge as a viable therapeutic approach to treat AD and other central nervous
      system disorders. We report here the use of a linear polyethyleneimine (LPEI)-g
      polyethylene glycol (PEG) copolymer-based micellar nanoparticle system to deliver
      siRNA targeting BACE1 and APP, two therapeutic targets of AD. Using LPEI-siRNA
      nanoparticles against either BACE1 or APP in cultured mouse neuroblastoma (N2a)
      cells, we observe selective knockdown, respectively, of BACE1 or APP. The
      encapsulation of siRNA by LPEI-g-PEG carriers, with different grafting degrees of
      PEG, leads to the formation of micellar nanoparticles with distinct morphologies,
      including worm-like, rod-like, or spherical nanoparticles. By infusing these
      shaped nanoparticles into mouse lateral ventricles, we show that rod-shaped
      nanoparticles achieved the most efficient knockdown of BACE1 in the brain.
      Furthermore, such knockdown is evident in spinal cords of these treated mice.
      Taken together, our findings indicate that the shape of siRNA-encapsulated
      nanoparticles is an important determinant for their delivery and gene knockdown
      efficiency in the central nervous system. 

PMID- 25965553
TI  - Chromosome microduplication in somatic cells decreases the genetic stability of
      human reprogrammed somatic cells and results in pluripotent stem cells.
AB  - Human pluripotent stem cells, including cloned embryonic and induced pluripotent
      stem cells, offer a limitless cellular source for regenerative medicine. However,
      their derivation efficiency is limited, and a large proportion of cells are
      arrested during reprogramming. In the current study, we explored chromosome
      microdeletion/duplication in arrested and established reprogrammed cells. Our
      results show that aneuploidy induced by somatic cell nuclear transfer technology
      is a key factor in the developmental failure of cloned human embryos and primary
      colonies from implanted cloned blastocysts and that expression patterns of
      apoptosis-related genes are dynamically altered. Overall, ~20%-53% of arrested
      primary colonies in induced plurpotent stem cells displayed aneuploidy, and
      upregulation of P53 and Bax occurred in all arrested primary colonies.
      Interestingly, when somatic cells with pre-existing chromosomal mutations were
      used as donor cells, no cloned blastocysts were obtained, and additional
      chromosomal mutations were detected in the resulting iPS cells following long
      term culture, which was not observed in the two iPS cell lines with normal
      karyotypes. In conclusion, aneuploidy induced by the reprogramming process
      restricts the derivation of pluripotent stem cells, and, more importantly, pre
      existing chromosomal mutations enhance the risk of genome instability, which
      limits the clinical utility of these cells. 

PMID- 25965554
TI  - Mn2+-doped prussian blue nanocubes for bimodal imaging and photothermal therapy
      with enhanced performance.
AB  - Prussian blue (PB) as a clinically adapted agent recently has drawn much
      attention in cancer theranostics for potential applications in magnetic resonance
      (MR) imaging as well as photothermal cancer treatment. In this work, we take a
      closer look at the imaging and therapy performance of PB agents once they are
      doped with Mn2+. It is found that Mn2+-doped PB nanocubes exhibit increased
      longitudinal relaxivity along with enhanced optical absorption red-shifted to the
      near-infrared (NIR) region. Those properties make PB:Mn nanocubes with
      appropriate surface coatings rather attractive agents for biomedical imaging and
      cancer therapy, which have been successfully demonstrated in our in vivo
      experiments for effectively tumor ablation.

PMID- 25965555
TI  - The Influence of Dimensional Effects on the Composition and Properties of
      Polydicarbonfluoride.
AB  - The influence of dimensional effects on the compositions and properties of
      polydicarbonfluoride (C2 F)n prepared from multilayered graphenes was
      investigated. Multilayered graphenes were produced by destructive thermal
      decomposition of intercalation compounds of "idealized" (C2 F)n that were
      obtained by reaction of gaseous ClF3 with natural graphite at a room temperature.
      The precursors of multilayered graphenes have a common formula (C2 F?xR)n where R
      is an organic or inorganic component. It was shown that polydicarbonfluoride
      prepared from multilayered graphene does not form stable intercalation compound
      with ClF3 , in contrast to polydicarbonfluoride prepared from graphite, that
      forms its intercalation compound with ClF3 during fluorination of initial
      graphite in the ClF3 excess. Investigations of polydicarbonfluoride prepared from
      multilayered graphene showed that it cannot form intercalation compounds with
      different classes of organic and inorganic compounds as polydicarbonfluoride
      prepared from graphite can do. The absence of such intercalation activity for
      polydicarbonfluoride prepared from multilayered graphene can be explained by high
      exfoliation degree of multilayered graphene (3-4 nm) along the c-axis that
      results in the presence of two-dimensional (2D) structure properties in
      multilayered graphene. Dimensional effects transformed the chemical properties of
      polydicarbonfluoride prepared from multilayered graphene and lowered its
      decomposition temperature by 150 K in comparison with polydicarbonfluoride
      prepared from graphite. 

PMID- 25965558
TI  - 3D Imaging of Twin Domain Defects in Gold Nanoparticles.
AB  - Topological defects are ubiquitous in physics and include crystallographic
      imperfections such as defects in condensed matter systems. Defects can determine
      many of the material's properties, thus providing novel opportunities for defect
      engineering. However, it is difficult to track buried defects and their
      interfaces in three dimensions with nanoscale resolution. Here, we report three
      dimensional visualization of gold nanocrystal twin domains using Bragg coherent X
      ray diffractive imaging in an aqueous environment. We capture the size and
      location of twin domains, which appear as voids in the Bragg electron density, in
      addition to a component of the strain field. Twin domains can interrupt the
      stacking order of the parent crystal, leading to a phase offset between the
      separated parent crystal pieces. We utilize this phase offset to estimate the
      roughness of the twin boundary. We measure the diffraction signal from the
      crystal twin and show its Bragg electron density fits into the parent crystal
      void. Defect imaging will likely facilitate improvement and rational design of
      nanostructured materials. 

PMID- 25965559
TI  - Disrupted Balance of MMPs/TIMPs in Gastric Carcinogenesis-Paradoxical Low MMP-2
      Expression in Tumor and Stromal Compartments as a Potential Marker of Unfavorable
      Outcome.
AB  - The aim of the study was to find correlations between MMP/TIMP reactivity and the
      expression of angiogenic factors, and relationships between these parameters and
      clinicopathological features of gastric cancer patients. Receiver Operating
      Characteristic curve analysis was used to find cut-off points that enabled fair
      decision-making in survival analysis. Low levels of MMP-2 expression in tumor and
      stromal compartments were significantly associated with poor prognosis-the
      probability that a patient would die within 60 months of surgery if their MMP-2
      was low, and was about 0.8 in both neoplastic and stromal compartments. 

PMID- 25965557
TI  - Reactive astrocytes as neural stem or progenitor cells: In vivo lineage, In vitro
      potential, and Genome-wide expression analysis.
AB  - Here, we review the stem cell hallmarks of endogenous neural stem cells (NSCs)
      during development and in some niches of the adult mammalian brain to then
      compare these with reactive astrocytes acquiring stem cell hallmarks after
      traumatic and ischemic brain injury. Notably, even endogenous NSCs including the
      earliest NSCs, the neuroepithelial cells, generate in most cases only a single
      type of progeny and self-renew only for a rather short time in vivo. In vitro,
      however, especially cells cultured under neurosphere conditions reveal a larger
      potential and long-term self-renewal under the influence of growth factors. This
      is rather well comparable to reactive astrocytes in the traumatic or ischemic
      brain some of which acquire neurosphere-forming capacity including multipotency
      and long-term self-renewal in vitro, while they remain within their astrocyte
      lineage in vivo. Both reactive astrocytes and endogenous NSCs exhibit stem cell
      hallmarks largely in vitro, but their lineage differs in vivo. Both populations
      generate largely a single cell type in vivo, but endogenous NSCs generate neurons
      and reactive astrocytes remain in the astrocyte lineage. However, at some early
      postnatal stages or in some brain regions reactive astrocytes can be released
      from this fate restriction, demonstrating that they can also enact neurogenesis.
      Thus, reactive astrocytes and NSCs share many characteristic hallmarks, but also
      exhibit key differences. This conclusion is further substantiated by genome-wide
      expression analysis comparing NSCs at different stages with astrocytes from the
      intact and injured brain parenchyma.

PMID- 25965561
TI  - Linkage disequilibrium with HLA-DRB1-DQB1 haplotypes explains the association of
      TNF-308G>A variant with type 1 diabetes in a Brazilian cohort.
AB  - BACKGROUND: A functional variant in the promoter region of the gene encoding
      tumor necrosis factor (TNF; rs1800629, -308G>A) showed to confer susceptibility
      to T1D. However, TNF rs1800629 was found, in several populations, to be in
      linkage disequilibrium with HLA susceptibility haplotypes to T1D. We evaluated
      the association of TNF rs1800629 with T1D in a cohort of Brazilian subjects, and
      assessed the impact of HLA susceptibility haplotypes in this association.
      METHODS: 659 subjects with T1D and 539 control subjects were genotyped for TNF
      308G>A variant. HLA-DRB1 and HLA-DQB1 genes were genotyped in a subset of 313
      subjects with T1D and 139 control subjects. RESULTS: Associations with T1D were
      observed for the A-allele of rs1800629 (OR 1.69, 95% CI 1.33-2.15, p<0.0001, in a
      codominant model) and for 3 HLA haplotypes: DRB1*03:01-DQB1*02:01 (OR 5.37, 95%
      CI 3.23-8.59, p<0.0001), DRB1*04:01-DQB1*03:02 (OR 2.95, 95% CI 1.21-7.21,
      p=0.01) and DRB1*04:02-DQB1*03:02 (OR 2.14, 95% CI 1.02-4.50, p=0.04). Linkage
      disequilibrium was observed between TNF rs1800629 and HLA-DRB1 and HLA-DQB1
      alleles. In a stepwise regression analysis HLA haplotypes, but not TNF rs1800629,
      remained independently associated with T1D. CONCLUSION: Our results do not
      support an independent effect of allelic variations of TNF in the genetic
      susceptibility to T1D.

PMID- 25965560
TI  - Human paraoxonase-1 (PON1): Gene structure and expression, promiscuous activities
      and multiple physiological roles.
AB  - Human PON1 is a HDL-associated lipolactonase capable of preventing LDL and cell
      membrane oxidation and is therefore considered to be atheroprotective. PON1
      contributes to the antioxidative function of HDL and reductions in HDL-PON1
      activity, prevalent in a wide variety of diseases with an inflammatory component,
      are believed to lead to dysfunctional HDL which can promote inflammation and
      atherosclerosis. However, PON1 is multifunctional and may contribute to other HDL
      functions such as in innate immunity, preventing infection by quorum sensing gram
      negative bacteria by destroying acyl lactone mediators of quorum sensing, and
      putative new roles in cancer development and the promotion of healthy ageing. In
      this review we explore the physiological roles of PON1 in disease development, as
      well as PON1 gene and protein structure, promiscuous activities and the roles of
      SNPs and ethnicity in determining PON1 activity. 

PMID- 25965562
TI  - Genotypic characterization of Brazilian patients with infantile and juvenile
      forms of metachromatic leukodystrophy.
AB  - Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder inherited as
      an autosomal recessive trait. MLD is caused by the deficiency of arylsulfatase A
      (ARSA), a lysosomal enzyme that catalyzes the first step in the degradation of
      sulfated glycolipids, which are essential components of the myelin sheet.
      Notably, between 7% and 15% of healthy individuals show in vitro deficiency of
      ARSA, a condition called ARSA pseudodeficiency (ARSA-PD). To date, 151 ARSA-MLD
      mutations have been reported in the gene encoding ARSA (ARSA), among which
      IVS2+1G>A and P426L occur at high frequencies in most of the studied populations.
      The aim of this work was to identify ARSA mutant alleles in a cohort of 27
      unrelated Brazilian MLD patients. The most frequent ARSA-MLD mutation, IVS2+1G>A,
      and the ARSA-PD polymorphisms, N350S and 1524+95A>G, were detected using real
      time PCR, while the remaining mutations were detected using direct sequencing of
      ARSA. In concordance with previous reports, IVS2+1G>A and P426L were the most
      common ARSA-MLD mutations in our cohort of MLD patients, found at frequencies of
      0.05 and 0.08, respectively. Interestingly, two mutations previously reported as
      rare, 103_110del8 and 1190_1191insC, were found at higher frequencies in our
      cohort of MLD patients, 0.08 and 0.06, respectively. Additionally, 11 other rare
      ARSA-MLD mutations were found at lower frequencies in our cohort of MLD patients.
      To our knowledge, this is the first systematic genotypic characterization of MLD
      patients from Latin America. This work highlights the genetic heterogeneity of
      MLD, and supports genotype-phenotype associations, which become more important as
      specific treatments are being developed for this devastating disorder.

PMID- 25965563
TI  - A patient with elderly-onset atypical hydroa vacciniforme with an indolent
      clinical course.
AB  - Hydroa vacciniforme (HV) is a rare photodermatosis that mainly affects children
      and manifests as vesiculopapular eruptions in sun-exposed areas without systemic
      symptoms. HV-like lymphoma (HVLL) is one of the Epstein-Barr virus (EBV)
      associated lymphoproliferative disorders (LPD) of childhood. Its diagnosis is
      based on monoclonal T-cell proliferation; however, its degree of malignancy is
      controversial owing to its variable prognosis. Elderly-onset cases of these
      diseases are extremely rare, and the clinical features remain unknown. It has
      been shown that late onset is closely associated with a severe phenotype in EBV
      associated LPD including atypical HV. Here we describe a case of elderly-onset
      atypical HV accompanied by T-cell monoclonality, but with a very indolent
      clinical course. Our patient indicates a possible case with elderly-onset
      atypical HV manifesting a favourable course, and that T-cell monoclonality and
      age of onset cannot always predict the disease severity, and highlights the
      difficulty of prognosis prediction in elderly-onset atypical HV. 

PMID- 25965565
TI  - Charting the "Splice" Routes to MDS.
AB  - Mutations in components of the 3' mRNA splicing machinery are found in almost 50%
      of myelodysplastic syndrome (MDS) cases. In this issue of Cancer Cell, Kim and
      colleagues, Colla and colleagues, and Shirai and colleagues report on the impact
      of mutated or dysregulated splicing factors to hematopoiesis, mRNA splicing, and
      MDS pathogenesis. 

PMID- 25965566
TI  - Functionally relevant RNA helicase mutations in familial and sporadic myeloid
      malignancies.
AB  - In this issue of Cancer Cell, Polprasert and colleagues identified recurrent
      mutations in the DEAD/H-box RNA helicase gene DDX41 in familial and acquired
      cases of myelodsyplasia and acute myeloid leukemia. These mutations induce
      defects in RNA splicing and represent a new class of mutations in myeloid
      malignancies. 

PMID- 25965564
TI  - Impact of the use of a rapid diagnostic test for visceral leishmaniasis on
      clinical practice in Ethiopia: a retrospective study.
AB  - BACKGROUND: Diagnostic guidelines for Visceral Leishmaniasis (VL) in the East
      African region are complex. Patients meeting the VL clinical case definition
      should be tested by rK39 rapid diagnostic test (RDT) followed by the Direct
      Agglutination Test (DAT) or tissue aspiration if RDT-negative. Otherwise, RDT
      positive patients should be started on VL treatment. We evaluated how this
      guideline is adhered to by assessing the routine clinical practice in a
      university hospital in North-West Ethiopia. METHODS: Retrospective record
      analysis was done for all patients who had an rK39-RDT done at University of
      Gondar (UoG) Hospital between June 2012 and June 2013. We described the
      diagnostic work-up performed and the proportion initiated on VL treatment by test
      result. RESULTS/FINDINGS: From a total of 928 patients tested, 308 (33.2%) were
      rK39 RDT-positive. Spleen or bone marrow aspiration was done for 237 (77.2%) RDT
      positive patients. Of these, 165 were confirmed parasitologically, yielding a
      positive predictive value of 69.6%. Only 126 (20.3%) of the 620 patients with a
      negative rK39 test underwent further testing by tissue aspiration, of which 22
      (17.5%) were also parasitology positive. HIV test results were available for 570
      (61.4%) patients and 36 (6.3%) were HIV-infected. Of the 187 parasitologically
      confirmed patients, 182 (97.3%) were started on VL treatment.
      CONCLUSIONS/DISCUSSION: A negative rK39 test was often not followed by further
      testing and a positive rK39 test result was followed by tissue aspiration in
      three out of four cases. Further research is required to understand why the
      diagnostic work-up did not comply with the guidelines, including evaluating
      adherence to the VL clinical case definition and quality of rK39-RDT testing.

PMID- 25965567
TI  - Convert and conquer: the strategy of chronic myelogenous leukemic cells.
AB  - Emerging evidence is contributing to explain how leukemias disrupt normal blood
      cell production. In this issue of Cancer Cell, Welner and colleagues show that,
      during the development of chronic myeloid leukemia, mutated cells transform
      normal hematopoietic progenitors into "leukemic like" cells through IL-6
      secretion, proposing a new cellular target. 

PMID- 25965568
TI  - Defining the molecular landscape of ependymomas.
AB  - Ependymomas have a variable prognosis. In this issue of Cancer Cell, Pajtler and
      colleagues identify nine subgroups of ependymoma using DNA methylation profiles.
      Two subgroups, predominately pediatric, are responsible for most of the
      mortality, with all others having nearly 100% overall survival after 5 years. 

PMID- 25965569
TI  - SRSF2 Mutations Contribute to Myelodysplasia by Mutant-Specific Effects on Exon
      Recognition.
AB  - Mutations affecting spliceosomal proteins are the most common mutations in
      patients with myelodysplastic syndromes (MDS), but their role in MDS pathogenesis
      has not been delineated. Here we report that mutations affecting the splicing
      factor SRSF2 directly impair hematopoietic differentiation in vivo, which is not
      due to SRSF2 loss of function. By contrast, SRSF2 mutations alter SRSF2's normal
      sequence-specific RNA binding activity, thereby altering the recognition of
      specific exonic splicing enhancer motifs to drive recurrent mis-splicing of key
      hematopoietic regulators. This includes SRSF2 mutation-dependent splicing of
      EZH2, which triggers nonsense-mediated decay, which, in turn, results in impaired
      hematopoietic differentiation. These data provide a mechanistic link between a
      mutant spliceosomal protein, alterations in the splicing of key regulators, and
      impaired hematopoiesis.

PMID- 25965570
TI  - Mutant U2AF1 Expression Alters Hematopoiesis and Pre-mRNA Splicing In Vivo.
AB  - Heterozygous somatic mutations in the spliceosome gene U2AF1 occur in ~ 11% of
      patients with myelodysplastic syndromes (MDS), the most common adult myeloid
      malignancy. It is unclear how these mutations contribute to disease. We examined
      in vivo hematopoietic consequences of the most common U2AF1 mutation using a
      doxycycline-inducible transgenic mouse model. Mice expressing mutant U2AF1(S34F)
      display altered hematopoiesis and changes in pre-mRNA splicing in hematopoietic
      progenitor cells by whole transcriptome analysis (RNA-seq). Integration with
      human RNA-seq datasets determined that common mutant U2AF1-induced splicing
      alterations are enriched in RNA processing genes, ribosomal genes, and
      recurrently mutated MDS and acute myeloid leukemia-associated genes. These
      findings support the hypothesis that mutant U2AF1 alters downstream gene isoform
      expression, thereby contributing to abnormal hematopoiesis in patients with MDS.

PMID- 25965571
TI  - Telomere dysfunction drives aberrant hematopoietic differentiation and
      myelodysplastic syndrome.
AB  - Myelodysplastic syndrome (MDS) risk correlates with advancing age, therapy
      induced DNA damage, and/or shorter telomeres, but whether telomere erosion
      directly induces MDS is unknown. Here, we provide the genetic evidence that
      telomere dysfunction-induced DNA damage drives classical MDS phenotypes and
      alters common myeloid progenitor (CMP) differentiation by repressing the
      expression of mRNA splicing/processing genes, including SRSF2. RNA-seq analyses
      of telomere dysfunctional CMP identified aberrantly spliced transcripts linked to
      pathways relevant to MDS pathogenesis such as genome stability, DNA repair,
      chromatin remodeling, and histone modification, which are also enriched in mouse
      CMP haploinsufficient for SRSF2 and in CD34(+) CMML patient cells harboring SRSF2
      mutation. Together, our studies establish an intimate link across telomere
      biology, aberrant RNA splicing, and myeloid progenitor differentiation. 

PMID- 25965572
TI  - Treatment of chronic myelogenous leukemia by blocking cytokine alterations found
      in normal stem and progenitor cells.
AB  - Leukemic cells disrupt normal patterns of blood cell formation, but little is
      understood about the mechanism. We investigated whether leukemic cells alter
      functions of normal hematopoietic stem and progenitor cells. Exposure to chronic
      myelogenous leukemia (CML) caused normal mouse hematopoietic progenitor cells to
      divide more readily, altered their differentiation, and reduced their
      reconstitution and self-renewal potential. Interestingly, the normal bystander
      cells acquired gene expression patterns resembling their malignant counterparts.
      Therefore, much of the leukemia signature is mediated by extrinsic factors.
      Indeed, IL-6 was responsible for most of these changes. Compatible results were
      obtained when human CML were cultured with normal human hematopoietic progenitor
      cells. Furthermore, neutralization of IL-6 prevented these changes and treated
      the disease. 

PMID- 25965573
TI  - Translational Activation of HIF1alpha by YB-1 Promotes Sarcoma Metastasis.
AB  - Metastatic dissemination is the leading cause of death in cancer patients, which
      is particularly evident for high-risk sarcomas such as Ewing sarcoma,
      osteosarcoma, and rhabdomyosarcoma. Previous research identified a crucial role
      for YB-1 in the epithelial-to-mesenchymal transition (EMT) and metastasis of
      epithelial malignancies. Based on clinical data and two distinct animal models,
      we now report that YB-1 is also a major metastatic driver in high-risk sarcomas.
      Our data establish YB-1 as a critical regulator of hypoxia-inducible factor
      1alpha (HIF1alpha) expression in sarcoma cells. YB-1 enhances HIF1alpha protein
      expression by directly binding to and activating translation of HIF1A messages.
      This leads to HIF1alpha-mediated sarcoma cell invasion and enhanced metastatic
      capacity in vivo, highlighting a translationally regulated YB-1-HIF1alpha axis in
      sarcoma metastasis.

PMID- 25965574
TI  - Cross-Species Genomics Identifies TAF12, NFYC, and RAD54L as Choroid Plexus
      Carcinoma Oncogenes.
AB  - Choroid plexus carcinomas (CPCs) are poorly understood and frequently lethal
      brain tumors with few treatment options. Using a mouse model of the disease and a
      large cohort of human CPCs, we performed a cross-species, genome-wide search for
      oncogenes within syntenic regions of chromosome gain. TAF12, NFYC, and RAD54L co
      located on human chromosome 1p32-35.3 and mouse chromosome 4qD1-D3 were
      identified as oncogenes that are gained in tumors in both species and required
      for disease initiation and progression. TAF12 and NFYC are transcription factors
      that regulate the epigenome, whereas RAD54L plays a central role in DNA repair.
      Our data identify a group of concurrently gained oncogenes that cooperate in the
      formation of CPC and reveal potential avenues for therapy. 

PMID- 25965576
TI  - MULTEM: A new multislice program to perform accurate and fast electron
      diffraction and imaging simulations using Graphics Processing Units with CUDA.
AB  - The main features and the GPU implementation of the MULTEM program are presented
      and described. This new program performs accurate and fast multislice simulations
      by including higher order expansion of the multislice solution of the high energy
      Schrodinger equation, the correct subslicing of the three-dimensional potential
      and top-bottom surfaces. The program implements different kinds of simulation for
      CTEM, STEM, ED, PED, CBED, ADF-TEM and ABF-HC with proper treatment of the
      spatial and temporal incoherences. The multislice approach described here treats
      the specimen as amorphous material which allows a straightforward implementation
      of the frozen phonon approximation. The generalized transmission function for
      each slice is calculated when is needed and then discarded. This allows us to
      perform large simulations that can include millions of atoms and keep the
      computer memory requirements to a reasonable level. 

PMID- 25965577
TI  - A new reversal mode in exchange coupled antiferromagnetic/ferromagnetic disks:
      distorted viscous vortex.
AB  - Magnetic vortices have generated intense interest in recent years due to their
      unique reversal mechanisms, fascinating topological properties, and exciting
      potential applications. In addition, the exchange coupling of magnetic vortices
      to antiferromagnets has also been shown to lead to a range of novel phenomena and
      functionalities. Here we report a new magnetization reversal mode of magnetic
      vortices in exchange coupled Ir20Mn80/Fe20Ni80 microdots: distorted viscous
      vortex reversal. In contrast to the previously known or proposed reversal modes,
      the vortex is distorted close to the interface and viscously dragged due to the
      uncompensated spins of a thin antiferromagnet, which leads to unexpected
      asymmetries in the annihilation and nucleation fields. These results provide a
      deeper understanding of the physics of exchange coupled vortices and may also
      have important implications for applications involving exchange coupled
      nanostructures. 

PMID- 25965578
TI  - Automatic segmentation of vessels from angiogram sequences using adaptive feature
      transformation.
AB  - This paper proposes an efficient method for automatically segmenting vessels from
      angiogram sequences. The method includes two steps: extracting high-contrast
      angiograms and segmenting vessels. First, we select high-contrast angiograms
      automatically using vessel intensity distribution. Based on multiscale Hessian
      based filtering, we propose an adaptive feature transformation function to
      improve the vesselness response. This method overcomes numerous problems, which
      exist in the X-ray angiograms by using the scale factors and transformed
      intensities. Various scales are established to mitigate variations of the
      intensity distribution. The transformed intensities are applied to coping with
      lower contrast and nonuniform intensity distribution. Finally, the connected
      component labeling method is used to extract the vessels. The proposed method can
      distinguish between the vessel and the background in a complex background. In our
      experiments, 20 angiogram sequences are used to evaluate the accuracy of the
      selected high-contrast angiogram. The accuracy of extracting high-contrast
      angiograms is 98%. For evaluating the accuracy of the segmentation results, 72
      angiograms were selected. The accuracy of the proposed segmentation method is
      96.3%. The Kappa value is 81.8%. After inspection by a cardiologist, the
      experimental results show that the proposed method can automatically and
      accurately segment vessels. 

PMID- 25965575
TI  - Molecular Classification of Ependymal Tumors across All CNS Compartments,
      Histopathological Grades, and Age Groups.
AB  - Ependymal tumors across age groups are currently classified and graded solely by
      histopathology. It is, however, commonly accepted that this classification scheme
      has limited clinical utility based on its lack of reproducibility in predicting
      patients' outcome. We aimed at establishing a uniform molecular classification
      using DNA methylation profiling. Nine molecular subgroups were identified in a
      large cohort of 500 tumors, 3 in each anatomical compartment of the CNS, spine,
      posterior fossa, supratentorial. Two supratentorial subgroups are characterized
      by prototypic fusion genes involving RELA and YAP1, respectively. Regarding
      clinical associations, the molecular classification proposed herein outperforms
      the current histopathological classification and thus might serve as a basis for
      the next World Health Organization classification of CNS tumors.

PMID- 25965579
TI  - On-surface reactions.
AB  - On-surface synthesis constitutes a rapidly growing field of research due to its
      promising application for creating stable molecular structures on surfaces. While
      self-assembled structures rely on reversible interactions, on-surface synthesis
      provides the potential for creating long-term stable structures with well
      controlled properties, for example superior electron transport for future
      molecular electronic devices. On-surface synthesis holds the promise for
      preparing insoluble compounds that cannot be produced in solution. Another highly
      exciting aspect of on-surface synthesis is the chance to discover new reaction
      pathways due to the two-dimensional confinement of the reaction educts. In this
      review, we discuss the current state-of-the-art and classify the reactions that
      have been successfully performed so far. Special emphasis is put on electrically
      insulating surfaces, as these substrates pose particular challenges for on
      surface synthesis while at the same time bearing high potential for future use,
      for example, in molecular electronics. 

PMID- 25965580
TI  - Increasing Redundancy Exponentially Reduces Error Rates during Algorithmic Self
      Assembly.
AB  - While biology demonstrates that molecules can reliably transfer information and
      compute, design principles for implementing complex molecular computations in
      vitro are still being developed. In electronic computers, large-scale computation
      is made possible by redundancy, which allows errors to be detected and corrected.
      Increasing the amount of redundancy can exponentially reduce errors. Here, we use
      algorithmic self-assembly, a generalization of crystal growth in which the self
      assembly process executes a program for growing an object, to examine
      experimentally whether redundancy can analogously reduce the rate at which errors
      occur during molecular self-assembly. We designed DNA double-crossover molecules
      to algorithmically self-assemble ribbon crystals that repeatedly copy a short
      bitstring, and we measured the error rate when each bit is encoded by 1 molecule,
      or redundantly encoded by 2, 3, or 4 molecules. Under our experimental
      conditions, each additional level of redundancy decreases the bitwise error rate
      by a factor of roughly 3, with the 4-redundant encoding yielding an error rate
      less than 0.1%. While theory and simulation predict that larger improvements in
      error rates are possible, our results already suggest that by using sufficient
      redundancy it may be possible to algorithmically self-assemble micrometer-sized
      objects with programmable, nanometer-scale features. 

PMID- 25965581
TI  - Asymmetric catalysis with silicon-based cuprates: enantio- and regioselective
      allylic substitution of linear precursors.
AB  - An enantio- and regioselective allylic silylation of linear allylic phosphates
      that makes use of catalytically generated cuprate-type silicon nucleophiles is
      reported. The method relies on soft bis(triorganosilyl) zincs as silicon
      pronucleophiles that are prepared in situ from the corresponding hard lithium
      reagents by transmetalation with ZnCl2 . With a preformed chiral N-heterocyclic
      carbene-copper(I) complex as catalyst, exceedingly high enantiomeric excesses are
      achieved. The new method is superior to existing ones using a silicon-boron
      reagent as the source of the silicon nucleophile. 

PMID- 25965582
TI  - TH1 and TH17 cells promote crescent formation in experimental autoimmune
      glomerulonephritis.
AB  - Autoimmunity against the Goodpasture antigen alpha3IV-NC1 results in crescentic
      glomerulonephritis (GN). Both antibodies and T cells directed against alpha3IV
      NC1 have been implicated in disease development and progression. Using the model
      of experimental autoimmune glomerulonephritis (EAG) in DBA/1 mice, we aimed to
      characterize the frequency and function of alpha3IV-NC1-specific CD4(+) T cells
      in the kidneys. DBA/1 mice repeatedly immunized with human alpha3IV-NC1 developed
      necrotizing/crescentic GN. Kidneys with crescentic GN contained CD4(+) cells
      responding to alpha3IV-NC1 with the production of IFN-gamma or IL-17A,
      demonstrating the accumulation of both alpha3IV-NC1-specific TH1 and TH17 cells.
      To test the functional relevance of TH1 and TH17 cells, EAG was induced in DBA/1
      mice deficient in IFN-gammaR, IL-17A or IL-23p19. Mice of all knockout groups
      mounted alpha3IV-NC1 IgG, developed nephrotic range proteinuria, and IgG
      deposition to the glomerular basement membranes at levels similar to immunized
      wild-type mice. However, all knockout groups showed significantly fewer
      glomerular crescents and attenuated tubulointerstitial damage. Our results
      suggest that both alpha3IV-NC1-specific TH1 and TH17 cells accumulate in the
      kidneys and are crucial for the development of necrotizing/crescentic GN.

PMID- 25965583
TI  - Relatively Small Contribution of Methylation and Genomic Copy Number Aberration
      to the Aberrant Expression of Inflammation-Related Genes in HBV-Related
      Hepatocellular Carcinoma.
AB  - BACKGROUND: It is well known that chronic inflammation plays a pivotal role in
      the development of hepatitis B virus (HBV) related hepatocellular carcinoma
      (HCC). However, the causes behind aberrant expression of inflammation-related
      genes occurred in HCC remain unclear. METHODS: We performed array-based analyses
      to comprehensively investigate the contributions of DNA methylation and somatic
      copy number aberration (SCNA) to the aberrant expression of 1,027 inflammation
      related genes in 30 HCCs and paired non-tumor tissues. The results were validated
      in public datasets and an additional sample set of 47 paired HCCs and non-tumor
      tissues. RESULTS: We identified 252 differentially expressed, 125 aberrantly
      methylated and 287 copy number changed inflammation-related genes. Despite
      reasonable statistical power, among them, only 11 genes and 56 genes whose
      aberrant expression was associated with DNA methylation or SCNA, respectively.
      DNA methylation and SCNA together contributed to less than 30% aberrant
      expression of inflammation-related genes. CONCLUSION: These results suggest that
      molecular mechanisms other than DNA methylation and SCNA might play major role in
      the regulation of aberrant expression of inflammation-related gene in HBV-related
      HCCs.

PMID- 25965584
TI  - Effect of noise in intelligent cellular decision making.
AB  - Similar to intelligent multicellular neural networks controlling human brains,
      even single cells, surprisingly, are able to make intelligent decisions to
      classify several external stimuli or to associate them. This happens because of
      the fact that gene regulatory networks can perform as perceptrons, simple
      intelligent schemes known from studies on Artificial Intelligence. We study the
      role of genetic noise in intelligent decision making at the genetic level and
      show that noise can play a constructive role helping cells to make a proper
      decision. We show this using the example of a simple genetic classifier able to
      classify two external stimuli. 

PMID- 25965585
TI  - Critical Casimir forces between planar and crenellated surfaces.
AB  - We study critical Casimir forces between planar walls and geometrically
      structured substrates within mean-field theory. As substrate structures,
      crenellated surfaces consisting of periodic arrays of rectangular crenels and
      merlons are considered. Within the widely used proximity force approximation,
      both the top surfaces of the merlons and the bottom surfaces of the crenels
      contribute to the critical Casimir force. However, for such systems the full,
      numerically determined critical Casimir forces deviate significantly from the
      pairwise addition formalism underlying the proximity force approximation. A first
      order correction to the proximity force approximation is presented in terms of a
      step contribution arising from the critical Casimir interaction between a planar
      substrate and the right-angled steps of the merlons consisting of their upper and
      lower edges as well as their sidewalls. 

PMID- 25965586
TI  - Negative Epistasis between Sickle and Foetal Haemoglobin Suggests a Reduction in
      Protection against Malaria.
AB  - BACKGROUND: Haemoglobin variants, Sickle (HbS) and foetal (HbF) have been
      associated with malaria protection. This study explores epistatic interactions
      between HbS and HbF on malaria infection. METHODS: The study was conducted
      between March 2004 and December 2013 within the sickle cell disease (SCD)
      programme at Muhimbili National Hospital, Tanzania. SCD status was categorized
      into HbAA, HbAS and HbSS using hemoglobin electrophoresis and High Performance
      Liquid Chromatography (HPLC). HbF levels were determined by HPLC. Malaria was
      diagnosed using rapid diagnostic test and/or blood film. Logistic regression and
      generalized estimating equations models were used to evaluate associations
      between SCD status, HbF and malaria. FINDINGS: 2,049 individuals with age range 0
      70 years, HbAA 311(15.2%), HbAS 241(11.8%) and HbSS 1,497(73.1%) were analysed.
      At enrolment, malaria prevalence was significantly higher in HbAA 13.2% compared
      to HbAS 1.24% and HbSS 1.34% (p<0.001). Mean HbF was lower in those with malaria
      compared to those without malaria in HbAA (0.43% vs 0.82%) but was the reverse in
      HbSS (8.10% vs 5.59%). An increase in HbF was associated with a decrease in risk
      of malaria OR=0.50 (95%CI: 0.28, 0.90; p=0.021) in HbAA, whereas for HbSS the
      risk of malaria increased OR=2.94 (1.44, 5.98; p=0.003). A similar pattern was
      seen during multiple visits; HbAA OR=0.52 (0.34, 0.80; p=0.003) vs HbSS OR=2.01
      (1.27, 3.23; p=0.003). CONCLUSION: Higher prevalence of malaria in HbAA compared
      to HbAS and HbSS confirmed the protective effect of HbS. Lower prevalence of
      malaria in HbAA with high HbF supports a protective effect of HbF. However, in
      HbSS, the higher prevalence of malaria with high levels of HbF suggests loss of
      malaria protection. This is the first epidemiological study to suggest a negative
      epistasis between HbF and HbS on malaria.

PMID- 25965587
TI  - Experimental Correlation of Substrate Position with Reaction Outcome in the
      Aliphatic Halogenase, SyrB2.
AB  - The iron(II)- and 2-(oxo)glutarate-dependent (Fe/2OG) oxygenases catalyze an
      array of challenging transformations, but how individual members of the enzyme
      family direct different outcomes is poorly understood. The Fe/2OG halogenase,
      SyrB2, chlorinates C4 of its native substrate, l-threonine appended to the
      carrier protein, SyrB1, but hydroxylates C5 of l-norvaline and, to a lesser
      extent, C4 of l-aminobutyric acid when SyrB1 presents these non-native amino
      acids. To test the hypothesis that positioning of the targeted carbon dictates
      the outcome, we defined the positions of these three substrates by measuring
      hyperfine couplings between substrate deuterium atoms and the stable, EPR-active
      iron-nitrosyl adduct, a surrogate for reaction intermediates. The Fe-(2)H
      distances and N-Fe-(2)H angles, which vary from 4.2 A and 85 degrees  for
      threonine to 3.4 A and 65 degrees  for norvaline, rationalize the trends in
      reactivity. This experimental correlation of position to outcome should aid in
      judging from structural data on other Fe/2OG enzymes whether they suppress
      hydroxylation or form hydroxylated intermediates on the pathways to other
      outcomes. 

PMID- 25965588
TI  - The association of red blood cell distribution width with drug-eluting stent
      restenosis in unstable angina pectoris patients.

PMID- 25965589
TI  - Ticagrelor-induced acute generalized exanthematous pustulosis.

PMID- 25965590
TI  - Underuse and overuse of anticoagulation for atrial fibrillation: A study in
      Indigenous and non-Indigenous Australians.
AB  - BACKGROUND: Atrial fibrillation (AF) is a leading cause of preventable stroke in
      Australia. Given that anticoagulation therapy can significantly reduce this
      stroke risk, we sought to characterise anticoagulation use in Indigenous and non
      Indigenous Australians with AF. METHODS: Administrative, clinical and
      prescription data from patients with AF were linked. Anticoagulation use was
      characterised according to guideline-recommended risk scores and Indigenous
      status. RESULTS: 19,613 individuals with AF were studied. Despite a greater
      prevalence of other risk factors, Indigenous Australians were significantly
      younger than their non-Indigenous counterparts (p<0.001) and thus had lower
      CHADS2- (1.19+/-0.32 vs 1.99+/-0.47, p<0.001) and CHA2DS2VASc-scores (1.47 +/-
      0.03 vs 2.82 +/- 0.08, p<0.001). Correspondingly, the percentage of Indigenous
      Australians with CHADS2 >= 2 (39.6% vs 44.1%, p<0.001) and CHA2DS2VASc-scores >=
      2 (62.9% vs 78.8%, p<0.001) was also lower. Indigenous Australians, however, had
      greater rates of under- and over-anticoagulation. Overall, 72.1% and 68.9% of
      Indigenous and non-Indigenous Australians with CHADS2 scores >=2, and 76.3% and
      71.3% with CHA2DS2VASc scores >=2, were under-anticoagulated. Similarly, 27.4%
      and 24.1% of Indigenous and non-Indigenous Australians with CHADS2 scores=0, and
      24.0% and 16.7% with CHA2DS2VASc-scores=0, were over-anticoagulated. In
      multivariate analyses, Indigenous Australians were more likely to receive under-
      or over-anticoagulation according to CHADS2- or CHA2DS2VASc-score (p=0.045 and
      p<0.001 respectively). CONCLUSION: Anticoagulation for AF is frequently not
      prescribed in accordance with guideline recommendations. Under-anticoagulation in
      those at high stroke risk, and over-anticoagulation in those at low risk, is
      common and more likely in Indigenous patients with AF. Improving adherence to
      guideline recommendations for anticoagulation in AF may reduce both ischaemic and
      haemorrhagic strokes in Indigenous and non-Indigenous Australians.

PMID- 25965591
TI  - "Mariana Trench" T-waves.

PMID- 25965592
TI  - Ethnic differences in arterial stiffness the Helius study.
AB  - OBJECTIVE: Well-known ethnic differences in cardiovascular risk exist, which may
      be explained by ethnic differences in arterial stiffness. Our aim was to assess
      ethnic differences in arterial stiffness, to explore whether these differences
      are accounted for by conventional cardiovascular risk factors, and study whether
      they differ across age. METHODS: Cross-sectional data of 1797 Dutch, 1846 South
      Asian Surinamese, 1840 African Surinamese, and 1673 Ghanaian participants of the
      observational HELIUS study (aged 18-70 years) were used. Arterial stiffness was
      assessed by duplicate pulse wave velocity (PWV) measurements using the
      Arteriograph system. RESULTS: Linear regression showed that South-Asian
      Surinamese had higher PWVs as compared with Dutch (age-adjusted mean difference
      (95% CI) was 0.55 (0.39-0.70) m/s in men and 0.82 (0.63-1.01) m/s in women).
      These differences were largely, but not completely, explained by conventional
      risk factors (particularly age and MAP). These ethnic differences were not found
      at young age (<35 years). African Surinamese and Ghanaians had higher PWVs as
      compared with Dutch across the entire age range (ranging from 0.22 (0.06-0.39)
      m/s in African Surinamese men to 1.07 (0.89-1.26) m/s in Ghanaian women), but
      these differences disappeared or reversed after adjustment for risk factors.
      CONCLUSIONS: PWV levels paralleled the well-known ethnic differences in
      cardiovascular risk. After adjustment for cardiovascular risk factors, however,
      these ethnic differences in PWV largely disappear. Together with the absence of
      ethnic differences in PWV at young age, our results support the hypothesis that
      higher PWV in South-Asian and African ethnic groups develops due to higher
      exposure to cardiovascular risk factors.

PMID- 25965593
TI  - Bosentan in pulmonary hypertension secondary to unilateral absence of a pulmonary
      artery.

PMID- 25965594
TI  - SIRT1 suppresses cardiomyocyte apoptosis in diabetic cardiomyopathy: An insight
      into endoplasmic reticulum stress response mechanism.
AB  - BACKGROUND: Endoplasmic reticulum (ER) stress-dependent apoptosis had been shown
      to occur in the hearts of people with diabetes, although the exact mechanisms are
      unclear. Sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide NAD(+)-dependent
      deacetylase, is known to play a role in diabetes-related complications as well as
      ER-stress. Therefore, we investigated the relationship between Sirtuin 1 (SIRT1)
      and ER stress-induced apoptosis in H9C2 cardiomyocyte. METHODS: Diabetic rats
      were established by a single intraperitoneal injection of streptozotocin (STZ;
      50mg/kg) with high-fat diet. For in vitro analysis, rat derived H9C2
      cardiomyocytes were cultured. Cardiac function was assessed by Doppler, and SIRT1
      as well as ER stress related protein expressions were measured by
      immunohistochemistry and western blotting. Cultured cells were exposed to
      advanced glycation end products (AGEs) (400MUg/mL) for inducing ER stress and
      apoptosis. Cell apoptosis were detected by flow cytometry. RESULTS: In vivo, ER
      stress was enhanced in the cardiomyocytes of diabetic rats without any
      treatments. A SIRT1 activator, resveratrol, could significantly restore cardiac
      function, reduce cardiomyocyte apoptosis, and ameliorate ER stress. In vitro, we
      showed that apoptosis and ER stress increased after AGE stimulation when SIRT1
      expression was downregulated by short interfering RNA (siRNA) (p<0.05). However,
      resveratrol (10MUM) restored SIRT1 levels in cardiomyocytes and markedly reduced
      ER stress-mediated apoptosis. CONCLUSION: SIRT1 may attenuate ER stress-induced
      cardiomyocyte apoptosis via PERK/eIF2alpha, ATF6/CHOP, and IRE1alpha/JNK-mediated
      pathways. This study may provide insights into a novel underlying mechanism and a
      strategy for treating diabetic cardiomyopathy.

PMID- 25965595
TI  - Impairment of Global and Regional Longitudinal Strains in patients with Myotonic
      Dystrophy type 1.

PMID- 25965596
TI  - The role of circulatory power and cardiac reserve in reverse epidemiology -
      Assessing heart failure severity.

PMID- 25965597
TI  - Inter-arm blood pressure difference and all-cause or cardiovascular mortality.

PMID- 25965598
TI  - Effects of statin therapy on ascending aorta aneurysms growth: A propensity
      matched analysis.
AB  - BACKGROUND: Pleiotropic effects of statins have been advocated for remodeling of
      the vascular wall. The aim of the present study was to investigate whether statin
      therapy influences the growth rate of ascending aorta (AA) diameter. METHODS: A
      total of 1348 patients was referred to our outpatient clinic for initial AA
      ectasia from September 2005 to December 2011. A propensity score was built to
      perfectly match (1:1) patients administered (Group A) or not (Group B) with
      statin therapy. Clinical and echocardiographic follow-up was 100% completed at 3
      years after the first visit. Treatment groups were investigated for differences
      in AA maximum diameter, furthermore rates of survival free from death and/or
      complications were assessed by Kaplan-Meier analysis. RESULTS: Finally, two
      fairly-comparable groups of 329 patients each were obtained (Propensity model c
      statistic 0.86, p<0.0001). At baseline, mean AA diameters were 38.88 +/- 2.48 mm
      and 39.09 +/- 2.60 mm in Groups A and B, respectively. At 3-years, similar rates
      of hypertension control (86 +/- 12% vs. 85 +/- 14%) were found, whilst growth
      rate of AA diameter was +2.84 +/- 1.33 mm (or +0.95 mm/year) in Group A and +3.80
      +/- 1.69 mm (or +1.27 mm/year) in Group B (p<0.0001). Three-year survival free
      from the composite outcome (death, dissection/rupture, need for operative repair)
      was found to be significantly improved in Group A (85.4 +/- 2.0%) rather than in
      Group B (79.7 +/- 2.2%), with a log-rank p=0.05 (HR 0.69, 95% CI 0.47 to 1.01).
      CONCLUSIONS: In this study, statin treatment is associated with reduced growth
      rate of ascending aorta aneurysms. The latter resulted in improved survival free
      from complications for patients receiving statins.

PMID- 25965599
TI  - Side effects of ticagrelor: Sinus node dysfunction with ventricular pause.

PMID- 25965600
TI  - Initial real world experience with a novel insertable (Reveal LinQ(@Medtronic))
      compared to the conventional (Reveal XT(@Medtronic)) implantable loop recorder at
      a tertiary care center - Points to ponder!
AB  - INTRODUCTION: Limited data is available regarding the novel Reveal LinQ (LinQ)
      which is a new generation implantable loop recorders (ILRs). METHODS: We
      performed a prospective, observational study of all consecutive patients
      undergoing conventional (Reveal XT; XT) and LinQ devices at our institution
      between January 2012 and December 2014. RESULTS: A total of 217 patients
      underwent ILR implantation. XT was implanted in 105 and LinQ in 112 patients.
      There were no significant differences in baseline characteristics between the two
      groups. LinQ implantation using the manufacturer's technique termed,
      "manufacturer's method" group had significantly higher incidence of pocket
      infection compared to XT (6/50, 12% vs 3/105, 3%, p=0.032). With modifications to
      the LinQ implantation technique (using a conventional scalpel and placing a
      suture when needed to the incision) termed "modified method" group, the rate of
      infection has decreased significantly compared to "manufacturer's method group"
      (0/62, 0% vs 6/50, 12%, p=0.004) (Table 3). In multivariate regression analysis,
      the only independent predictors of infection were younger age (OR 0.95; p=0.04),
      insertion of LinQ device (OR 30.02; p=0.006) and procedure time (OR 1.07;
      p=0.03). CONCLUSION: In our single-center, prospective, observational study we
      found that with the current implantable techniques, the novel insertable LinQ
      device is associated with increased risk of complications.

PMID- 25965601
TI  - Direct, inflammation-mediated and blood-pressure-mediated effects of total and
      abdominal adiposity on diastolic function: EPIPorto study.
AB  - BACKGROUND: Obesity has been associated with subclinical diastolic dysfunction
      and increased risk of heart failure. Our aims were to evaluate the age- and sex
      specific role of total and abdominal adiposity on diastolic function and to
      assess the direct and indirect pathophysiological mechanisms involved in this
      association. METHODS AND RESULTS: Within a population-based study (EPIPorto), a
      total of 1063 individuals aged >= 45 years (62% female; 62.4 +/- 10.6 years) were
      evaluated using echocardiography, anthropometrics, electrical bioimpedance and
      blood tests. Diastolic function was assessed with using EAE/ASE consensus
      criteria. Worse diastolic function grades were associated with increased BMI, fat
      mass % and waist-to-height ratio (p for trend<0.001). The inverse association
      between adiposity and diastolic function was stronger in men and in the younger
      population. In multivariate analysis, waist-to-height ratio (per cm/cm) was
      associated with reduced E' velocity (adjusted beta: -14.4; 95% CI: -21.1 to -7.6;
      p<0.001) and increased E/E' ratio (adjusted beta: 9.7, 95% CI: 5.4-10.0;
      p<0.001), among men<65 years. Both direct and indirect mechanisms were involved
      in the E' velocity decrease by waist-to-height ratio in participants<65 years.
      The effect was mainly direct in men (81.3%), while it was mostly indirect in
      women, through systolic blood pressure (50.8%) and inflammation (15.1%).
      CONCLUSIONS: Adiposity, especially abdominal, was associated with worse diastolic
      function. This association was more important in men and in the younger
      population. The causal mechanisms involved were sex-specific, with mostly direct
      effects among men and blood-pressure-mediated among women.

PMID- 25965602
TI  - Psychiatric co-morbidities in patients with dilated cardiomyopathy.

PMID- 25965603
TI  - Could breastfeeding be protective for cardiovascular disease?

PMID- 25965604
TI  - Drug-coated balloon without stent implantation for chronic total occlusion of
      coronary arteries: Description of a new strategy with an optical coherence
      tomography assistance.

PMID- 25965605
TI  - Prognostic value of epsilon waves in lead aVR in arrhythmogenic cardiomyopathy.

PMID- 25965606
TI  - Successful primary PCI after simultaneous two vessel subacute stent thrombosis,
      despite continuous dual antiplatelet therapy.

PMID- 25965607
TI  - Pre-participation screening and athlete's heart: A long way to run.

PMID- 25965608
TI  - Treatment strategy of spontaneous coronary artery dissection: Conservative or
      interventional.

PMID- 25965609
TI  - Percutaneous mitral annuloplasty in a patient with coronary sinus stenosis and
      coronary artery compression during procedure; they will not interfere.

PMID- 25965610
TI  - Seven essential tools of a cardiologist's survival kit.

PMID- 25965611
TI  - Prolonged right ventricular ejection delay identifies high risk patients and
      gender differences in Brugada syndrome.
AB  - BACKGROUND AND OBJECTIVES: Right ventricular (RV) conduction delay has been
      suggested as an underlying pathophysiological mechanism in Brugada syndrome (BS).
      In this cross-sectional study we non-invasively assessed the value of
      echocardiographic markers reflecting ventricular ejection delay to further assess
      electromechanical abnormalities in BS and to identify patients at risk for life
      threatening arrhythmic events. Furthermore, we sought to assess differences in
      ejection delays between genders because male BS patients demonstrate a more
      malignant clinical phenotype. METHODS: 124 BS patients (57.3% males) and 62
      controls (CTR) (48.4% males) were included. Using Tissue Velocity Imaging, the
      ejection delay, determined as the time from QRS onset to the onset of the
      sustained systolic contraction, was measured for both RV free wall (RVED) and
      lateral LV wall (LVED). From these parameters, the interventricular ejection
      delay between both walls (IVED) was calculated. RESULTS: BS patients had longer
      RVEDs and IVEDs compared to the CTR. BS patients with a previous history of
      syncope or spontaneous ventricular arrhythmia showed the longest RVEDs and IVEDs.
      Male BS patients demonstrated longer RVEDs and IVEDs than females. Male BS
      patients with malignant events had the longest delays. No significant differences
      regarding LVED were observed between BS patients and CTR. CONCLUSIONS: We
      demonstrated that a previous history of malignant events was associated with
      longer RVEDs. Our findings supported the RV conduction delay mechanism behind BS
      and demonstrated for the first time that the predominant malignant male Brugada
      phenotype might also be the result of a more delayed RV conduction in males.

PMID- 25965612
TI  - Impact of serum tenascin-C on the aortic healing process during the chronic stage
      of type B acute aortic dissection.

PMID- 25965613
TI  - Association of age and baseline systolic blood pressure with outcomes in patients
      hospitalized for acute heart failure syndromes.
AB  - BACKGROUND: Baseline systolic blood pressure (SBP) is one of the most important
      prognostic indicators for patients with acute heart failure syndromes (AHFS).
      However, the association among age, baseline SBP, and outcomes of AHFS is
      unclear. This study was performed to evaluate the relation between baseline SBP
      and outcomes to increasing age in patients hospitalized for AHFS. METHODS: Of the
      4842 patients entered into the Acute Decompensated Heart Failure Syndromes
      (ATTEND) registry, 4828 patients with in-hospital and postdischarge follow-up
      data were included. The patients were divided into quartiles of age (<65, 65 to
      75, 76 to 82, and >=83 years), and each age group was divided into quartiles of
      baseline SBP. Then the 1-year all-cause mortality was compared among the baseline
      SBP quartiles in the each age quartile. RESULTS: After adjustment for multiple
      comorbidities, patients aged <65 years, 65 to 75 years, and 76 to 82 years showed
      no significant increase in the relative risk of all-cause mortality as the
      baseline SBP declined until the lowest SBP quartile (SBP<112 mmHg, <120 mmHg, and
      <120 mmHg, respectively). In contrast, among patients aged >=83 years, the lower
      three SBP quartiles (SBP<122 mmHg, 122 to <142 mmHg, and 142 to <165 mmHg) were
      associated with a significantly higher risk of all-cause mortality than the
      highest SBP quartile. CONCLUSIONS: In patients hospitalized for AHFS, the
      relation between baseline SBP and all-cause mortality is markedly associated with
      increasing age, which means that baseline SBP is more important for very elderly
      patients with AHFS.

PMID- 25965614
TI  - Thrombolysis In Myocardial Infarction Frame Count in Takotsubo Cardiomyopathy.

PMID- 25965615
TI  - RDW as a marker of postoperative atrial fibrillation.

PMID- 25965616
TI  - "Left ventricular filling pressure(s)" - Ambiguous and misleading terminology,
      best abandoned.
AB  - The use of the terms "left ventricular filling pressure" and "left ventricular
      filling pressures" is widespread in the cardiology literature, but the meanings
      ascribed to these terms have not been consistent. Left ventricular end-diastolic
      pressure (LVEDP) and mean left atrial pressure (LAP) cannot be used
      interchangeably as they will often differ in magnitude in the presence of cardiac
      disease and they also have different clinical significance. LVEDP is the best
      pressure to use when considering left ventricular function, whereas mean LAP is
      the most relevant pressure when considering the tendency to pulmonary congestion.
      The mean LAP is also the most relevant pressure for determining whether pulmonary
      hypertension has a left heart (post-capillary) component. If only a left
      ventricular pressure tracing is available then a technique to measure the mean
      left ventricular diastolic pressure is the best option for estimating the mean
      LAP. If only right heart pressures are available then the pulmonary artery end
      diastolic pressure will provide a reasonable estimate of LVEDP, but only when the
      heart and pulmonary circulation are normal. If there is mitral valve disease,
      left ventricular disease or pulmonary hypertension the LVEDP cannot be estimated
      from right heart pressures. The problem of the ambiguity of "filling pressure
      (s)" is readily solved by the abandonment of this term and the use of either
      LVEDP or mean LAP as appropriate. 

PMID- 25965617
TI  - Stress-induced cardiomyopathy presented with acute decompensated heart failure.

PMID- 25965618
TI  - Supernormal conduction in the left bundle branch block revealed by relatively
      late atrial extrasystoles.

PMID- 25965619
TI  - Continuous positive airway pressure treatment reduces cardiovascular death and
      non-fatal cardiovascular events in patients with obstructive sleep apnea: A meta
      analysis of 11 studies.

PMID- 25965620
TI  - Hemodynamic, not ventilatory, inefficiency is associated with high VE/VCO2 slope
      in repaired, noncyanotic congenital heart disease.
AB  - BACKGROUND: A high slope of the ventilation vs. carbon dioxide relationship
      (VE/VCO2 slope) during incremental exercise has been reported in several
      congenital heart disease (CHD) types, but it is not clear whether the main cause
      of high VE/VCO2 slope is excessive ventilation or reduced perfusion. METHODS: We
      studied 169 adolescent and adult patients with repaired, noncyanotic CHD, divided
      into 2 groups according to VE/VCO2 slope %predicted values (<=120 and >120), and
      15 age- and sex-matched normals. VCO2/VE max and VO2/VE max were considered
      proxies of the perfusion/ventilation relationship, with VCO2 and VO2 as indirect
      descriptors of cardiac output. RESULTS: VCO2/VE max was significantly and
      inversely related to VE/VCO2 slope (r=-0.73, p<0.0001), and higher in normals and
      <=120 than in >120 (39.6 +/- 7.7, 36.1 +/- 5.3 and 28.5 +/- 4.1, respectively,
      p<0.0001). Similarly, VCO2 at VCO2/VE max was higher in normals and <=120 than in
      >120 (1701 +/- 474, 1480 +/- 492 and 1169 +/- 388 ml/min, respectively,
      p<0.0001), whereas ventilation at VCO2/VE max showed no changes (43 +/- 8, 41 +/-
      12, 41 +/- 11 and 41 +/- 9l/min, respectively, p=0.82) between groups. Thus,
      differences in VCO2/VE max and VE/VCO2 slope between groups were due mostly to
      changes in VCO2, i.e. in cardiac output, rather than ventilation. The same
      behavior was observed for VO2/VE max. CONCLUSIONS: A high VE/VCO2 slope observed
      in patients with repaired, noncyanotic CHD seems not to depend on excessive
      ventilation but on hypoperfusion due to impaired cardiac output response to
      incremental exercise. This finding should focus researchers' attention mainly on
      the heart when addressing exercise pathophysiology of this patient population.

PMID- 25965621
TI  - Effects of add-on lipid-modifying therapy on top of background statin treatment
      on major cardiovascular events: A meta-analysis of randomized controlled trials.
AB  - BACKGROUND: In patients at high risk of atherosclerotic cardiovascular diseases
      (ASCVDs), residual cardiovascular risk persists despite the achievement of target
      LDL cholesterol levels with statin therapy. It is still unclear whether adding
      lipid-modifying agent to statin treatment can further improve clinical outcomes.
      METHODS: Randomized controlled trials (RCTs) in terms of adding lipid-modifying
      agent to statin versus statin monotherapy in patients at high risk of ASCVD were
      identified by electronic and manual searches. Results were expressed as relative
      risk (RR) with 95% confidence intervals (CIs). RESULTS: Eleven RCTs with 109,244
      patients were included in this meta-analysis. Overall, the incidences of major
      adverse cardiovascular events (MACEs) were 9.70% in the statin combination groups
      and 9.92% in the statin monotherapy groups. No significant difference was
      observed in the risk of MACEs either in overall (RR 0.99, 95% CI 0.93-1.05,
      P=0.76) or subgroup analysis (CETP inhibitor: RR 1.07, 95% CI 0.93-1.23, P=0.37;
      niacin: RR 1.03, 95% CI 0.85-1.25, P=0.79; n-3 fatty acid: RR 0.98, 95% CI 0.88
      1.09, P=0.70; fenofibrate: RR 0.93, 95% CI 0.80-1.09, P=0.38), with the exception
      of the statin/ezetimibe combination subgroup (RR 0.92, 95% CI 0.87-0.97,
      P=0.004). Adding lipid-modifying agent to statin significantly increased liver
      injury risk. Adding ezetimibe to statin did not alter side effect profile.
      CONCLUSION: Adding niacin, CETP inhibitors, n-3 fatty acid or fibrates to statin
      therapy has all failed to achieve a clinical benefit. Adding ezetimibe to statin
      therapy further lowers LDL-cholesterol safely and translates into a clinical
      benefit in patients at high risk of ASCVD.

PMID- 25965622
TI  - Massive left ventricular calcification.

PMID- 25965623
TI  - The mechanisms of spontaneous termination of reentrant supraventricular
      tachycardias.
AB  - BACKGROUND: Atrioventricular nodal reentrant tachycardia (AVNRT) and
      atrioventricular reentrant tachycardia (AVRT) often terminate spontaneously,
      presumably due to changes in the electrophysiological properties of the reentrant
      circuit. However, the mechanism of spontaneous termination of these arrhythmias
      is incompletely understood. METHODS: We included 70 consecutive patients with
      reentrant supraventricular tachycardias (35 AVNRT, 35 AVRT) in whom the
      arrhythmia ended spontaneously during the electrophysiologic study. We determined
      in each patient the duration of the induced arrhythmia, site of block, beat-to
      beat oscillations in tachycardia cycle-length (CL), A-H, H-V, H-A and V-A
      intervals. RESULTS: In 21/34 (62%) patients with AVNRT and 19/30 (63%) with
      orthodromic AVRT, tachycardia termination was preceded by progressive increase in
      tachycardia CL due to prolongation of the A-H interval (Mobitz type-I pattern).
      In 13/34 patients with AVNRT (38%) and 11/30 with orthodromic AVRT (37%),
      termination occurred suddenly without a preceding change in CL, with block
      ensuing retrogradely either in the fast AV nodal pathway or the accessory pathway
      (Mobitz type-II pattern). In 4/5 patients with antidromic AVRT the tachycardia
      ended at the retrograde limb with previous prolongation of the VA interval.
      CONCLUSION: Spontaneous termination of AVNRT and AVRT is a time-related
      phenomenon. Despite different pathways being involved in these two reentrant
      tachycardias, termination can follow antegrade or retrograde block in similar
      ratio (60% antegradely and 40% retrogradely). Antegrade block is preceded by
      prolongation of the AH interval (Mobitz type-I), whereas retrograde block occurs
      unexpectedly in the retrograde limb (Mobitz type-II). Fatigue of conduction
      appears to be involved in this phenomenon.

PMID- 25965624
TI  - Prognostic impact of established and novel renal function biomarkers in
      myocardial infarction with cardiogenic shock: A biomarker substudy of the IABP
      SHOCK II-trial.
AB  - BACKGROUND: In cardiogenic shock (CS) renal dysfunction is an important parameter
      of inadequate end-organ perfusion and an independent predictor of adverse
      outcome. Early detection of renal dysfunction is therefore important, and novel
      biomarkers such as Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney
      Injury Molecule 1 (KIM1) and Cystatin C (CysC) have been suggested. However, in
      high-risk CS patients their role for assessing renal injury has not yet been
      investigated in comparison to the most widely used serum creatinine. METHODS:
      This predefined substudy included 190 patients of the randomized Intraaortic
      Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II)-trial. Blood samples were
      collected directly during primary percutaneous coronary intervention, one day and
      two days after randomization. The primary endpoint for outcome assessment was 1
      year mortality. RESULTS: Creatinine, NGAL and KIM-1 were significantly higher in
      non-survivors in comparison to survivors over time in ANOVA (p<0.001; p=0.002 and
      p=0.04, respectively). In contrast, CysC levels were not associated with the
      primary endpoint (p=0.15). Receiver operator characteristics revealed that
      creatinine at any time point had the best predictive value for 1 year mortality.
      This was also true when comparing creatinine to different equations for
      glomerular filtration rate. In multivariable Cox-regression analysis creatinine
      remained the only significant independent predictor of kidney biomarkers of time
      to death during the first year. CONCLUSIONS: Assessment of novel biomarkers such
      as CysC, NGAL and KIM-1 or calculation of glomerular filtration rate provide no
      additional prognostic information in patients with CS complicating acute
      myocardial infarction in comparison to creatinine.

PMID- 25965625
TI  - Spontaneous healing of spontaneous coronary artery dissection after balloon
      angioplasty: Follow-up for over 9 months using optical coherence tomography and
      intravascular ultrasound.

PMID- 25965626
TI  - Further elucidation on "Hybrid ABSORB bioresorbable vascular scaffold and drug
      eluting stent or hybrid BVS-DES percutaneous coronary intervention: Method and
      rationale for hybrid overlapping PCI".

PMID- 25965628
TI  - Diastolic bicycle stress echocardiography: Normal reference values in a middle
      age population.

PMID- 25965627
TI  - Prognostic impact of venous thromboembolism in patients with Duchenne muscular
      dystrophy: Prospective multicenter 5-year cohort study.

PMID- 25965629
TI  - Delirium tremens is a risk factor for Takotsubo cardiomyopathy.

PMID- 25965630
TI  - Cardiac troponin elevation predicts all-cause mortality in patients with acute
      exacerbation of chronic obstructive pulmonary disease: Systematic review and meta
      analysis.
AB  - BACKGROUND: Cardiovascular disease, especially ischemic heart disease, is a major
      comorbidity in chronic obstructive pulmonary disease (COPD) patients. Several
      studies suggested that after acute exacerbation of COPD (AECOPD), there is a
      significant increase of mortality (cardiac and all-cause) and of myocardial
      infarction. Whether cardiac troponin (Tn) elevation during AECOPD could be
      considered a prognostic marker of all-cause mortality is still debated. METHODS:
      To assess the prognostic role of cardiac Tn elevation during AECOPD, we performed
      a systematic review and meta-analysis. We included studies with patients admitted
      to the hospital for AECOPD, with at least one Tn assessment and reporting the
      relationship (after multivariable analysis) between Tn elevation and all-cause
      mortality. Secondarily, studies were stratified according to: i) type of troponin
      (Tn I or Tn T), and ii) follow-up length (<=6 months vs. >6 months). RESULTS: Ten
      studies were included in the systematic review and 8 in the meta-analysis.
      Cardiac Tn elevation ranges from 18% to 73%. We found that cardiac Tn elevation
      was significantly related to an increased risk for all-cause mortality (OR 1.69;
      95% CI 1.25-2.29; I(2) 40%). This finding was independent to the follow-up length
      of studies (<=6 months: OR 3.22; 95% CI 1.31-7.91; >6 months: OR 1.38; 95% CI
      1.02-1.86). Finally, Tn T seems to be more helpful in predicting all-cause
      mortality as compared to Tn I (OR 1.54; 95% CI 1.2-1.96 vs. OR 3.39, 95% CI 0.86
      13.36, respectively). CONCLUSIONS: In patients admitted to the hospital for
      AECOPD, cardiac Tn elevation emerged as an independent predictor of increased
      risk of all-cause mortality.

PMID- 25965631
TI  - Adverse clinical course and poor prognosis of hypertrophic cardiomyopathy due to
      mutations in FHL1.

PMID- 25965632
TI  - Hydrous mineral dehydration around heat-generating nuclear waste in bedded salt
      formations.
AB  - Heat-generating nuclear waste disposal in bedded salt during the first two years
      after waste emplacement is explored using numerical simulations tied to
      experiments of hydrous mineral dehydration. Heating impure salt samples to
      temperatures of 265  degrees C can release over 20% by mass of hydrous minerals
      as water. Three steps in a series of dehydration reactions are measured (65, 110,
      and 265  degrees C), and water loss associated with each step is averaged from
      experimental data into a water source model. Simulations using this dehydration
      model are used to predict temperature, moisture, and porosity after heating by
      750-W waste canisters, assuming hydrous mineral mass fractions from 0 to 10%. The
      formation of a three-phase heat pipe (with counter-circulation of vapor and
      brine) occurs as water vapor is driven away from the heat source, condenses, and
      flows back toward the heat source, leading to changes in porosity, permeability,
      temperature, saturation, and thermal conductivity of the backfill salt
      surrounding the waste canisters. Heat pipe formation depends on temperature,
      moisture availability, and mobility. In certain cases, dehydration of hydrous
      minerals provides sufficient extra moisture to push the system into a sustained
      heat pipe, where simulations neglecting this process do not. 

PMID- 25965633
TI  - International college of prosthodontists growing its global presence.

PMID- 25965634
TI  - A new classification system for all-ceramic and ceramic-like restorative
      materials.
AB  - Classification systems for all-ceramic materials are useful for communication and
      educational purposes and warrant continuous revisions and updates to incorporate
      new materials. This article proposes a classification system for ceramic and
      ceramic-like restorative materials in an attempt to systematize and include a new
      class of materials. This new classification system categorizes ceramic
      restorative materials into three families: (1) glass-matrix ceramics, (2)
      polycrystalline ceramics, and (3) resin-matrix ceramics. Subfamilies are
      described in each group along with their composition, allowing for newly
      developed materials to be placed into the already existing main families. The
      criteria used to differentiate ceramic materials are based on the phase or phases
      present in their chemical composition. Thus, an all-ceramic material is
      classified according to whether a glass-matrix phase is present (glass-matrix
      ceramics) or absent (polycrystalline ceramics) or whether the material contains
      an organic matrix highly filled with ceramic particles (resin-matrix ceramics).
      Also presented are the manufacturers' clinical indications for the different
      materials and an overview of the different fabrication methods and whether they
      are used as framework materials or monolithic solutions. Current developments in
      ceramic materials not yet available to the dental market are discussed. 

PMID- 25965635
TI  - Clinical evaluation of tooth-supported zirconia-based fixed dental prostheses: a
      retrospective cohort study from the AIOP clinical research group.
AB  - PURPOSE: The aim of this retrospective cohort study was to evaluate the clinical
      performance of tooth-supported zirconia-based fixed dental prostheses (FDPs) made
      by 15 members of the Italian Academy of Prosthetic Dentistry over a time period
      of up to 5 years. MATERIALS AND METHODS: Ninety-eight patients were treated with
      a total of 137 zirconia-based FDPs in anterior and posterior regions using
      primarily chamfer or knife-edge tooth preparations. The cohort group with
      parafunctional habits was compared with patients without parafunctional habits
      according to the esthetic, functional, and biologic United States Public Health
      Service criteria modified by the FDI World Dental Federation. RESULTS: The
      estimated cumulative survival of all restorations was 94.70% +/- 1.25% standard
      error (SE), whereas the estimated cumulative success decreased to 89.78% +/- 2.58
      SE. Mechanical failures, including three zirconia framework fractures, two
      hairline cracks, nine chippings, and one delamination of the ceramic veneering,
      were recorded during the 1- to 5-year observation period. An odds ratio of 2.02
      (95% confidence interval: 0.67 to 6.12) showed a moderate association between
      parafunction and failure. CONCLUSIONS: Zirconia-based tooth-supported FDPs showed
      promising clinical results over a period of up to 5 years. Technical
      complications were more commonly detected in patients with parafunctional habits.

PMID- 25965636
TI  - Clinical evaluation of zirconia-based restorations on implants: a retrospective
      cohort study from the AIOP clinical research group.
AB  - PURPOSE: The aim of this retrospective cohort study was to evaluate the clinical
      performance of zirconia-based implant-supported single crowns and fixed dental
      prostheses (FDPs) made by 15 members of the Italian Academy of Prosthetic
      Dentistry (AIOP) over a time period of up to 5 years. MATERIALS AND METHODS: One
      hundred thirty-one patients were treated with a total of 210 zirconia-based
      single crowns and FDPs on implants in anterior and posterior regions. A cohort
      group with parafunctional habits was compared with patients without
      parafunctional habits according to the esthetic, functional, and biologic United
      States Public Health Service criteria modified by the FDI World Dental
      Federation. RESULTS: The estimated cumulative survival (ECS) and standard error
      (SE) of all restorations on implants was 91.95% +/- 1.39%, and the estimated
      cumulative success (ECSs) and SE was 88.37% +/- 1.72%. The ECS of single crowns
      and FDPs was 91.25% +/- 3.69% and 95.23% +/- 2.28%, respectively, and the
      estimated cumulative success rates were 88.84% +/- 2.05% and 87.96% +/- 3.16%,
      respectively. Mechanical failures, including four zirconia core fractures, three
      hairline cracks, four chippings, and five delaminations of the ceramic veneering
      material, were recorded during a 1- to 5-year observation period. The odds ratio
      of 3.39 (95% confidence interval: 1.18 to 9.73) showed a moderate association
      between parafunction and failure. CONCLUSIONS: Zirconiabased implant-supported
      restorations showed encouraging clinical results over a period of up to 5 years,
      but more clinical data are needed before these restorations can be considered a
      viable treatment alternative. Mechanical failures were primarily observed in
      patients with parafunctions.

PMID- 25965637
TI  - The commissure line of the mouth for orienting the occlusal plane.
AB  - This study investigated the positional relation of the commissure line of the
      mouth to the maxillary first molars. Thirty-five volunteers, 20 to 40 years old,
      with normal natural dentitions were recruited. Maxillary casts with marks
      locating the commissure were digitally scanned to measure the vertical distance
      from the tip to the base of the mesiofacial cusp (CO) and from the tip to the
      mark (CM). There was no significant difference (t test; P > .05) between the CO
      (1.61 +/- 0.41 mm) and CM (1.14 +/- 0.68 mm). The mean distance of the commissure
      mark from the occlusal plane was 0.78 mm. 

PMID- 25965638
TI  - Fixed prosthodontic treatment outcomes in the long-term management of patients
      with periodontal disease: a 20-year follow-up report.
AB  - PURPOSE: The aim of this long-term cohort study was to evaluate the efficacy and
      complications of fixed partial dentures in a convenience sample of 100 patients
      with periodontal disease who were treated and maintained periodontal patients
      after 20 years. MATERIALS AND METHODS: After active treatment, including
      periodontal surgery and endodontic and prosthetic treatment, patients were
      enrolled in a supportive periodontal care (SPC) program with 3- to 6-month
      recalls. All patients showed clinical data recorded at (1) the original
      consultation (T0), (2) the first SPC visit following the completion of prosthetic
      treatment (T1), and (3) at the latest SPC clinical session 20 years after T1
      (T2). Multivariate analyses were performed to investigate the influence of
      clinical variables on the risk of prosthetic abutment (PA) loss after 20 years'
      visits. RESULTS: The final sample comprised 100 patients. At T1, a total of 948
      PAs represented the original sample of experimental teeth. At the 20-year follow
      up, a total of 854 PAs (90.1%) were still in function, while 94 (9.9%) PAs in 41
      patients (41%) were lost during SPC; 98% of lost PA were endodontically treated.
      Vertical root fracture (48%) was the major cause of PA loss, while progression of
      periodontitis caused 31% of PA loss. Age (P = .002), Full-Mouth Plaque Score (P <
      .0001), Full-Mouth Bleeding Score (P = .0002), and oral parafunctions (P = .0083)
      were associated with increased probability of PA failure. Among clinical-related
      factors, endodontic treatment (P = .0082), root resection/ amputation (P <
      .0001), multi-rooted teeth (P = .0005), and abutment associated with parafunction
      (P < .0001) were associated with increased risk of abutment loss after 20 years.
      CONCLUSIONS: Perioprosthetic treatment in compliant patients is highly successful
      after 20 years of SPC.

PMID- 25965639
TI  - Tooth loss prior to radiation in relation to tumor location in patients with head
      and neck cancer.
AB  - PURPOSE: This study aimed to investigate the impact of preradiation tooth loss in
      patients with head and neck cancer. MATERIALS AND METHODS: Records of 397
      (partially) dentate patients who were referred for preradiation oral screening
      were included. Number and location of teeth lost and occluding pairs lost were
      determined for different tumor locations. RESULTS: The majority of patients (54%)
      were affected by tooth loss. Proportion of teeth lost, their location, and
      proportion of occluding pairs lost were not evenly distributed across tumor
      locations. The highest proportions of teeth were removed with oral tumors
      (maxilla: 25%; mandible: 47%). For preradiation preventive extractions only, ie,
      not taking into account teeth that were lost due to ablative surgery, tooth loss
      in the mandible was still not evenly distributed across tumor locations, but
      tooth loss in the maxilla and occluding pairs lost were. CONCLUSIONS: Tumor
      location affects preradiation tooth loss, though this is primarily a consequence
      of ablative surgery rather than a consequence of preradiation dental extraction
      decisions. Since patients with oral cavity tumors are affected most by
      preradiation tooth loss, treatment planning with regard to functional
      rehabilitation is desirable for this patient group in particular.

PMID- 25965640
TI  - Remaining coronal dentin and risk of fiber-reinforced composite post-core
      restoration failure: a meta-analysis.
AB  - PURPOSE: The amount of coronal residual structure has been recognized as critical
      to the survival probability of pulpless teeth. The aim of this study was to
      analyze whether and how coronal dentin loss would affect the failure rate of
      fiber-reinforced composite (FRC) post-core restorations. MATERIALS AND METHODS:
      Eligible studies were searched in PubMed, Cochrane Library, Embase, and China
      National Knowledge Infrastructure databases from their inception through April
      2014. The risk ratio with 95% confidence interval (CI) was estimated using the
      Mantel and Haenszel method. RESULTS: Five studies were included in this meta
      analysis. The risk ratio for coronal wall absence was 2.73 (95% CI: 1.48-5.03).
      The risk ratio for ferrule absence was 1.94 (95% CI: 0.57-6.54). CONCLUSIONS:
      This meta-analysis of the limited studies available suggested that coronal wall
      absence might increase the risk of FRC post-core restoration failure, while the
      role of ferrule effect is still not entirely understood.

PMID- 25965641
TI  - Viscoelastic properties and antimicrobial effects of soft liners with silver
      zeolite in complete dental prosthesis wearers: an in vivo study.
AB  - PURPOSE: This study aimed to compare the viscoelastic properties and
      antimicrobial activity of a soft liner with and without silver zeolite for a
      period of 4 weeks. MATERIALS AND METHODS: Thirty edentulous patients wearing
      complete dental prostheses were selected. A uniform space was created in the
      intaglio surface of their maxillary prosthesis, and a soft liner without silver
      zeolite (control material: S) was applied. After 28 days, the soft liner was
      replaced with new soft liner containing silver zeolite (test material: SZ) and
      worn for another period of 28 days. Viscoelastic analysis was conducted on the
      prostheses using S and SZ materials for newly formed samples (T0) and on samples
      collected after the 28-day period (T28). Culture tests were performed on both
      materials at T28. Statistical analysis was done using Student independent t test.
      RESULTS: The decrease in elasticity from T0 to T28 was found to be 76.49% and
      79.11% and the decrease in viscosity was 76.49% and 80.3% for the S and SZ
      materials, respectively. Hence, the difference was not significant. The mean
      colony-forming units (CFUs) of Candida albicans and gram-negative bacteria in the
      S material at T28 days was 3,150 +/- 1,251, whereas that of the SZ material was
      1,084 +/- 662. There was a statistically significant difference in the mean CFUs
      between the two groups (P < .05). CONCLUSIONS: The addition of silver zeolite to
      the soft liner improved the antimicrobial activity while not affecting
      significantly its viscoelastic properties.

PMID- 25965642
TI  - Different types of antagonists modify the outcome of complete denture renewal.
AB  - PURPOSE: The effect of renewing removable dentures on masticatory function was
      evaluated according to the occlusion offered by different types of mandibular
      arches. MATERIALS AND METHODS: Twenty-eight patients with complete maxillary
      dentures were subdivided into three groups in terms of mandibular dentition type:
      dentate, partial denture, and complete denture. The participants were observed
      before and 8 weeks after maxillary denture renewal. The mandibular denture was
      also renewed in the partial and complete denture groups. The participants
      masticated carrots, peanuts, and three model foods of different hardnesses. The
      particle size distribution of the boluses obtained from natural foods was
      characterized by the median particle size (d50) in relation to the masticatory
      normative indicator (MNI). Chewing time (CT), number of chewing cycles (CC), and
      chewing frequency (CF) were video recorded. A self-assessment questionnaire for
      oral health-related quality of life (Geriatric Oral Health Assessment Index
      [GOHAI]) was used. Statistical analyses were carried out with a mixed model.
      RESULTS: Renewal of the dentures decreased d50 (P < .001). The number of
      participants with d50 values above the MNI cutoff decreased from 12 to 2 after
      renewal. Renewal induced an increase in mean CF while chewing model foods (P <
      .001). With all foods, renewal tended to affect CT, CC, and CF differently among
      the three groups (statistically significant renewal A~ group interactions). The
      GOHAI score increased significantly for all groups. CONCLUSIONS: Denture renewal
      improves masticatory function. The complete denture group benefited least from
      renewal; the dentate group benefited most. This study confirmed the usefulness of
      denture renewal for improving functions and oral health- related quality of life.

PMID- 25965644
TI  - Implant-abutment connection deformation after prosthetic procedures: an in vitro
      study.
AB  - This study tested the possible damage to the internal implant connection provoked
      by repeated disconnection and reconnection of prosthetic components. Using a
      light-structured scanner, connection deformation was inferred by threedimensional
      (3D) positional changes of a "reference" abutment before and after multiple dis-
      and reconnections. Measurements were taken after 1, 2, 5, 10, and 20 insertions
      of titanium abutments in 16 internal hexagon implants. Statistical analysis
      revealed that multiple dis- and reconnections could cause a deformation in the
      implant-abutment connection, proportional to the number of insertion procedures.
      However, below the threshold of 10 cycles, 3D deformation values were minimal. 

PMID- 25965643
TI  - Various cements and their effects on bond strength of zirconia ceramic to enamel
      and dentin.
AB  - Zirconia ceramic disks (Cercon) were fabricated using a computer-aided design/
      computer-assisted manufacture system and fitted to hard tooth tissues from
      freshly extracted bovine mandibular incisors using seven cements (zinc phosphate,
      zinc polycarboxylate, Eco-Link, Panavia F 2.0, Clearfil SA Cement, MaxCem Elite,
      and GC Fuji Plus) with various physicochemical and bonding properties. Bond
      strengths were determined using a universal testing machine (Hounsfield H5KS)
      with a 5,000-N head and a cutting knife speed of 0.5 mm per minute. The study
      showed that the strongest bond between zirconia ceramic and hard tooth tissues
      was obtained with Panavia F 2.0 adhesive cement based on 10 methacryloyloxydecyl
      dihydrogen phosphate monomer. 

PMID- 25965645
TI  - Survey of the use of statistical methods in the international journal of
      prosthodontics.
AB  - PURPOSE: This survey aimed to review how scientific articles were reported and to
      describe the types of statistical tests that had been recently and commonly used
      in The International Journal of Prosthodontics. MATERIALS AND METHODS: All 174
      articles published in 2012 and 2013 were hand-searched to identify scientific
      articles (n = 151) and those using at least one statistical test to explore
      results (n = 111). Editorials, letters, comments, erratum, and award proceedings
      were excluded. The number and type of statistical tests used within articles were
      collated, and the 10 commonly used methods were identified and described.
      RESULTS: Of the 151 scientific articles, 76% (n = 111) used at least one
      statistical test and 24% (n = 40) used qualitative methods. Up to 10 tests were
      used per article, with 237 in total, of which 36 were unique. The 10 most
      commonly used tests were analysis of variance (ANOVA; n = 34), survival analyses
      (n = 29), Student t test (n = 19), chi-square (n = 19), Mann-Whitney U (n = 14),
      logistic regression (n = 13), Wilcoxon signed rank (n = 12), Fisher exact (n =
      11), log-rank (n = 10), and Cox proportional hazards (n = 8), and they accounted
      for 71% (n = 169) of all tests used. CONCLUSIONS: The vast majority of articles
      published in recent years in The International Journal of Prosthodontics employed
      statistical analyses. Across 2 years, nearly 250 tests were completed, including
      36 unique tests. Statistical test use was common but diverse.

PMID- 25965646
TI  - Human Papillomavirus Vaccine-Induced Cytokine Messenger RNA Expression in
      Vaccinated Women.
AB  - The objective of this work was to evaluate the influence of human papillomavirus
      (HPV) vaccination on peripheral blood mononuclear cell (PBMC) proliferation and
      cytokine gene transcription. PBMCs isolated after HPV immunization were incubated
      with HPV vaccine, phytohemagglutinin, or buffer. Cell proliferation was assessed
      by MTT reduction assay. RNA was extracted from PBMCs, and the relative
      concentration of cytokine messenger RNA (mRNA) transcripts (IFN-beta, IFN-gamma,
      IL-12, TNF-alpha, IL-6, IL-17, or IL-10) relative to transcription of the beta
      actin gene was determined by real-time polymerase chain reaction. PBMC
      proliferation in response to HPV vaccine and PHA were greater than that observed
      in unstimulated cells (p<0.001). Cytokine mRNAs were upregulated in stimulated
      PBMC cultures. The median increase in vaccine-stimulated cultures was: IFN
      beta=334.4-fold; IL-12=46.33-fold; IFN-gamma=12.64-fold; IL-6=9.07-fold; IL
      17=7.33-fold; IL-10=6.47-fold; and TNF-alpha=2.36-fold. The IFN-beta expression
      was significantly higher (p<0.05). Proliferative PBMC responses and multiple
      cytokine gene expression were detected in women who received the HPV vaccine.

PMID- 25965647
TI  - Asymmetric dimethylarginine levels in patients with schizophrenia.

PMID- 25965648
TI  - Asymmetric dimethylarginine (ADMA) and treatment response relationship in male
      patients with first-episode schizophrenia: Author's reply.

PMID- 25965649
TI  - [Vascular lesions, part 2: Treatment, complications and associated syndromes].

PMID- 25965650
TI  - [Physicians see both pros and cons of health care financial management.
      Questionnaire study provides more insights--with starting point in controversial
      DN-article series].
AB  - In the spring of 2013, the Swedish journalist Maciej Zaremba wrote a series of
      articles criticizing the impact of NPM (New Public Management) on Swedish health
      care. The present study examines the views of experienced Swedish physicians
      (general practitioners and internal medicine speclialists) on the problems
      focused in Mr Zaremba's article series. The respondents (51 general practitioners
      and 61 internal medicine specialists) mention advantages as well as disadvantages
      with NPM in Swedish health care. The majority agrees that with NPM, physicians
      loose influence over health care governance to other professional groups. The
      majority disagree with the charge made by Mr Zaremba that NPM has had the effect
      of manipulating Swedish physicians away from the standards of good medical care. 

PMID- 25965651
TI  - [When the behavior becomes a patient safety risk].
AB  - A less discussed aspect of patient safety issues in Sweden has been the
      correlation between disruptive behaviour and adverse advents. Disruptive
      behaviour, according to international studies, can affect team collaboration and
      communication, and hence the safety of care. Disruptive behaviour also exists in
      Swedish health-care. Dealing with the problem requires acknowledgement of its
      existence, and international examples have shown how to identify and prevent
      disruptive behaviour among health care staff. 

PMID- 25965652
TI  - [Value creating management can restore physicians' influence. Promotes quality of
      care and patient needs].

PMID- 25965653
TI  - [A widespread innovation. Per-Ingvar Branemarks method now used worldwide].

PMID- 25965654
TI  - [Not Available].

PMID- 25965655
TI  - [Not Available].

PMID- 25965656
TI  - [Not Available].

PMID- 25965657
TI  - [The disease narrative at the center].

PMID- 25965658
TI  - [No risk for internship to be abolished without being replaced].

PMID- 25965659
TI  - [Shortcuts to new and better human beings?].

PMID- 25965660
TI  - [Lessons of a healthcare scandal. Team training for obstetric care].

PMID- 25965661
TI  - [Mental illness and violent crimes--not an uncomplicated connection].

PMID- 25965663
TI  - [Respect the industry's regulatory system].

PMID- 25965662
TI  - [Good obstetric care requires interdisciplinary collaboration].

PMID- 25965664
TI  - ["We do not question the regulatory process"].

PMID- 25965666
TI  - [Regional cancer centers in collaboration: The time is ripe for open reporting
      within pathology].

PMID- 25965668
TI  - Effects of microgravity on DNA damage response in Caenorhabditis elegans during
      Shenzhou-8 spaceflight.
AB  - PURPOSE: Space radiations and microgravity both could cause DNA damage in cells,
      but the effects of microgravity on DNA damage response to space radiations are
      still controversial. MATERIALS AND METHODS: A mRNA microarray and microRNA micro-
      array in dauer larvae of Caenorhabditis elegans (C. elegans) that endured
      spaceflight environment and space radiations environment during 16.5-day Shenzhou
      8 space mission was performed. RESULTS: Twice as many transcripts significantly
      altered in the spaceflight environment than space radiations alone. The majority
      of alterations were related to protein amino acid dephosphorylation and histidine
      metabolic and catabolic processes. From about 900 genes related to DNA damage
      response, 38 differentially expressed genes were extracted; most of them
      differentially expressed under spaceflight environment but not space radiations,
      although the identical directions of alteration were observed in both cases. cel
      miR-81, cel- miR-82, cel-miR-124 and cel-miR-795 were predicted to regulate DNA
      damage response through four different anti-correlated genes. CONCLUSIONS:
      Evidence was provided that, in the presence of space radiations, microgravity
      probably enhanced the DNA damage response in C. elegans by integrating the
      transcriptome and microRNome.

PMID- 25965667
TI  - MALT1 Protease Activity Is Required for Innate and Adaptive Immune Responses.
AB  - CARMA-BCL10-MALT1 signalosomes play important roles in antigen receptor signaling
      and other pathways. Previous studies have suggested that as part of this complex,
      MALT1 functions as both a scaffolding protein to activate NF-kappaB through
      recruitment of ubiquitin ligases, and as a protease to cleave and inactivate
      downstream inhibitory signaling proteins. However, our understanding of the
      relative importance of these two distinct MALT1 activities has been hampered by a
      lack of selective MALT1 protease inhibitors with suitable pharmacologic
      properties. To fully investigate the role of MALT1 protease activity, we
      generated mice homozygous for a protease-dead mutation in MALT1. We found that
      some, but not all, MALT1 functions in immune cells were dependent upon its
      protease activity. Protease-dead mice had defects in the generation of splenic
      marginal zone and peritoneal B1 B cells. CD4+ and CD8+ T cells displayed
      decreased T cell receptor-stimulated proliferation and IL-2 production while B
      cell receptor-stimulated proliferation was partially dependent on protease
      activity. In dendritic cells, stimulation of cytokine production through the
      Dectin-1, Dectin-2, and Mincle C-type lectin receptors was also found to be
      partially dependent upon protease activity. In vivo, protease-dead mice had
      reduced basal immunoglobulin levels, and showed defective responses to
      immunization with T-dependent and T-independent antigens. Surprisingly, despite
      these decreased responses, MALT1 protease-dead mice, but not MALT1 null mice,
      developed mixed inflammatory cell infiltrates in multiple organs, suggesting
      MALT1 protease activity plays a role in immune homeostasis. These findings
      highlight the importance of MALT1 protease activity in multiple immune cell
      types, and in integrating immune responses in vivo. 

PMID- 25965669
TI  - Plasma Membrane Proteolipid 3 Protein Modulates Amphotericin B Resistance through
      Sphingolipid Biosynthetic Pathway.
AB  - Invasive opportunistic fungal infections of humans are common among those
      suffering from impaired immunity, and are difficult to treat resulting in high
      mortality. Amphotericin B (AmB) is one of the few antifungals available to treat
      such infections. The AmB resistance mechanisms reported so far mainly involve
      decrease in ergosterol content or alterations in cell wall. In contrast,
      depletion of sphingolipids sensitizes cells to AmB. Recently, overexpression of
      PMP3 gene, encoding plasma membrane proteolipid 3 protein, was shown to increase
      and its deletion to decrease, AmB resistance. Here we have explored the
      mechanistic basis of PMP3 effect on AmB resistance. It was found that ergosterol
      content and cell wall integrity are not related to modulation of AmB resistance
      by PMP3. A few prominent phenotypes of PMP3 delete strain, namely, defective
      actin polarity, impaired salt tolerance, and reduced rate of endocytosis are also
      not related to its AmB-sensitivity. However, PMP3 overexpression mediated
      increase in AmB resistance requires a functional sphingolipid pathway. Moreover,
      AmB sensitivity of strains deleted in PMP3 can be suppressed by the addition of
      phytosphingosine, a sphingolipid pathway intermediate, confirming the importance
      of this pathway in modulation of AmB resistance by PMP3. 

PMID- 25965670
TI  - PEGylated Liposomes as Carriers of Hydrophobic Porphyrins.
AB  - Sterically stabilized liposomes (SSLs) (PEGylated liposomes) are applied as
      effective drug delivery vehicles. Understanding the interactions between
      hydrophobic compounds and PEGylated membranes is therefore important to determine
      the effectiveness of PEGylated liposomes for delivery of drugs or other bioactive
      substances. In this study, we have combined fluorescence quenching analysis (FQA)
      experiments and all-atom molecular dynamics (MD) simulations to study the effect
      of membrane PEGylation on the location and orientation of 5,10,15,20-tetrakis(4
      hydroxyphenyl)porphyrin (p-THPP) that has been used in our study as a model
      hydrophobic compound. First, we consider the properties of p-THPP in the presence
      of different fluid phosphatidylcholine bilayers that we use as model systems for
      protein-free cell membranes. Next, we studied the interaction between PEGylated
      membranes and p-THPP. Our MD simulation results indicated that the arrangement of
      p-THPP within zwitterionic membranes is dependent on their free volume, and p
      THPP solubilized in PEGylated liposomes is localized in two preferred positions:
      deep within the membrane (close to the center of the bilayer) and in the outer
      PEG corona (p-THPP molecules being wrapped with the polymer chains). Fluorescence
      quenching methods confirmed the results of atomistic MD simulations and showed
      two populations of p-THPP molecules as in MD simulations. Our results provide
      both an explanation for the experimental observation that PEGylation improves the
      drug-loading efficiency of membranes and also a more detailed molecular-level
      description of the interactions between porphyrins and lipid membranes. 

PMID- 25965671
TI  - Streptococcus gordonii DL1 adhesin SspB V-region mediates coaggregation via
      receptor polysaccharide of Actinomyces oris T14V.
AB  - Streptococcus gordonii SspA and SspB proteins, members of the antigen I/II
      (AgI/II) family of Streptococcus adhesins, mediate adherence to cysteine-rich
      scavenger glycoprotein gp340 and cells of other oral microbial species. In this
      article we investigated further the mechanism of coaggregation between S.
      gordonii DL1 and Actinomyces oris T14V. Previous mutational analysis of S.
      gordonii suggested that SspB was necessary for coaggregation with A. oris T14V.
      We have confirmed this by showing that Lactococcus lactis surrogate host cells
      expressing SspB coaggregated with A. oris T14V and PK606 cells, while L. lactis
      cells expressing SspA did not. Coaggregation occurred independently of expression
      of A. oris type 1 (FimP) or type 2 (FimA) fimbriae. Polysaccharide was prepared
      from cells of A. oris T14V and found to contain 1,4-, 4,6- and 3,4-linked
      glucose, 1,4-linked mannose, and 2,4-linked galactose residues. When immobilized
      onto plastic wells this polysaccharide supported binding of L. lactis expressing
      SspB, but not binding of L. lactis expressing other AgI/II family proteins.
      Purified recombinant NAVP region of SspB, comprising amino acid (aa) residues 41
      847, bound A. oris polysaccharide but the C-domain (932-1470 aa residues) did
      not. A site-directed deletion of 29 aa residues (Delta691-718) close to the
      predicted binding cleft within the SspB V-region ablated binding of the NAVP
      region to polysaccharide. These results infer that the V-region head of SspB
      recognizes an actinomyces polysaccharide ligand, so further characterizing a
      lectin-like coaggregation mechanism occurring between two important primary
      colonizers.

PMID- 25965672
TI  - A Transport and Lairage Model for Salmonella Transmission Between Pigs Applicable
      to EU Member States.
AB  - A model for the transmission of Salmonella between finisher pigs during transport
      to the abattoir and subsequent lairage has been developed, including novel
      factors such as environmental contamination and the effect of stress, and is
      designed to be adaptable for any EU Member State (MS). The model forms part of a
      generic farm-to-consumption model for Salmonella in pigs, designed to model
      potentially important risk factors and assess the effectiveness of interventions.
      In this article, we discuss the parameterization of the model for two case study
      MSs. For both MSs, the model predicted an increase in the average MS-level
      prevalence of Salmonella-positive pigs during both transport and lairage,
      accounting for a large amount of the variation between reported on-farm
      prevalence and reported lymph-node prevalence at the slaughterhouse. Sensitivity
      analysis suggested that stress is the most important factor during transport,
      while a number of factors, including environmental contamination and the dose
      response parameters, are important during lairage. There was wide variation in
      the model-predicted change in prevalence in individual batches; while the
      majority of batches (80-90%) had no increase, in some batches the increase in
      prevalence was over 70% and in some cases infection was introduced into
      previously uninfected batches of pigs. Thus, the model suggests that while the
      transport and lairage stages of the farm-to-consumption exposure pathway are
      unlikely to be responsible for a large increase in average prevalence at the MS
      level, they can have a large effect on prevalence at an individual-batch level. 

PMID- 25965673
TI  - 4-Substituent pyridine directed cobalt(II) azides: solvothermal synthesis,
      structure, and magnetic properties.
AB  - The structure and magnetism of three cobalt(ii)-azide complexes,
      [Co(N3)2(bepy)2]n (), [Co2(N3)4(vipy)4]n (), and [Co(N3)2(bipy)]n () were tuned
      by three structurally related 4-substituent pyridines, 4-benzylpyridine (bepy), 4
      vinyl pyridine (vipy), and 4,4'-bipyridine (bipy) as co-ligands in solvothermal
      reactions. With flexible benzyl as a substituent group of the pyridine co-ligand,
      a one-dimensional (1D) complex with double end-to-end (EE) azide-bridging Co(ii)
      chain is formed. While using a rigid but small vinyl group as the substituent, a
      distinct Co(ii)-azide chain with alternate double end-on (EO) and double EE azide
      bridges was obtained. Finally, when another pyridine group was used instead of
      the substituent incapable of coordinating in and , a bipyridine, it gave rise to
      a chiral complex with a three-dimensional (3D) diamondoid Co(ii)-azide framework
      further reinforced by the bipy ligand. Magnetic studies indicate
      antiferromagnetic interactions between the Co(ii) ions in the three complexes,
      but interestingly, weak antiferromagnetism origin of spin canting exists in at
      low temperatures. 

PMID- 25965674
TI  - The dynamic Allan Variance IV: characterization of atomic clock anomalies.
AB  - The number of applications where precise clocks play a key role is steadily
      increasing, satellite navigation being the main example. Precise clock anomalies
      are hence critical events, and their characterization is a fundamental problem.
      When an anomaly occurs, the clock stability changes with time, and this variation
      can be characterized with the dynamic Allan variance (DAVAR). We obtain the DAVAR
      for a series of common clock anomalies, namely, a sinusoidal term, a phase jump,
      a frequency jump, and a sudden change in the clock noise variance. These
      anomalies are particularly common in space clocks. Our analytic results clarify
      how the clock stability changes during these anomalies. 

PMID- 25965675
TI  - Single-resonator dual-frequency AIN-on-Si MEMS oscillators.
AB  - This paper reports on the design, implementation, and phase-noise optimization of
      low-power interface IC for dual-frequency oscillators that utilize two high
      quality factor (Q) width-extensional bulk acoustic modes of the same AlN-on
      silicon resonator. Two 0.5-MUm CMOS transimpedance amplifiers (TIA) have been
      designed, characterized, and interfaced with two dual-mode resonators operating
      at 35.5/105.7 MHz (first/third order modes) and 35.5/174.9 MHz (first/ fifth
      order modes). One TIA uses open-loop regulated cascode (RGC) topology in the
      first stage to enable low power operation, whereas the second one uses an
      inverter with shunt-shunt feedback to deliver higher gain with lower phase noise.
      An on-chip switching network is incorporated into each TIA to change the
      oscillation frequency based on the different phase shift. The effect of TIA on
      the phase-noise performance of oscillators is studied and compared for both
      topologies. The measured phase noise of low- and high-frequency modes at 1 kHz
      offset from carrier are -114 and -108 dBc/Hz for the 35/105 MHz oscillator, and 
      108 and -105 dBc/Hz for the 35/175 MHz oscillator, respectively, whereas the far
      from-carrier reaches below -140 dBc/Hz in all cases. 

PMID- 25965676
TI  - Multi-line transmission combined with minimum variance beamforming in medical
      ultrasound imaging.
AB  - Increasing medical ultrasound imaging frame rate is important in several
      applications such as cardiac diagnostic imaging, where it is desirable to be able
      to examine the temporal behavior of fast phases in the cardiac cycle. This is
      particularly true in 3-D imaging, where current frame rate is still much slower
      than standard 2-D, B-mode imaging. Recently, a method that increases frame rate,
      labeled multi-line transmission (MLT), was reintroduced and analyzed. In MLT
      scanning, the transmission is simultaneously focused at several directions. This
      scan mode introduces artifacts that stem from the overlaps of the receive main
      lobe with the transmit side lobes of additional transmit directions besides the
      one of interest. Similar overlaps occur between the transmit main lobe with
      receive side lobes. These artifacts are known in the signal processing community
      as cross-talk. Previous studies have concentrated on proper transmit and receive
      apodization, as well as transmit directions arrangement in the transmit event, to
      reduce the cross-talk artifacts. This study examines the possibility of using
      adaptive beamforming, specifically, minimum variance (MV) and linearly
      constrained minimum variance (LCMV) beamforming, to reduce the cross-talk
      artifacts, and maintain or even improve image quality characteristics. Simulation
      results, as well as experimental phantom and in vivo cardiac data, demonstrate
      the feasibility of reducing cross-talk artifacts with MV beamforming. The MV and
      LCMV results achieve superior spatial resolution, not only over other MLT methods
      with data-independent apodization, but even over that of single-line transmission
      (SLT) without receive apodization. The MV beamformer is shown to be less
      sensitive to wider transmit profiles required to reduce the transmit crosstalk
      artifacts. MV beamforming, combined with the wider transmit profiles, can provide
      a good approach for MLT scanning with reduced cross-talk artifacts, without
      compromising spatial resolution, and even improving it. We also demonstrate that
      the MV and LCMV beamformers lead to almost identical results. This is because of
      their very similar beampatterns, except for the sharp nullifying properties that
      the LCMV beamformer has around interfering beams. 

PMID- 25965677
TI  - Effects of reverberations and clutter filtering in pulsed Doppler using sparse
      sequences.
AB  - Duplex ultrasound is a modality in which an ultrasound system is used for
      simultaneous acquisition of both B-mode images and velocity (Doppler) data.
      Conventional duplex sequences interleave packets of B-mode and Doppler
      transmissions, producing undesirable gaps during B-mode interruptions. In recent
      years, several techniques have been proposed for avoiding such gaps by using
      sparse sequences, in which velocity spectra are generated from nonuniformly
      sampled Doppler data containing frequent B-mode interruptions. In this work, two
      negative effects are discussed that may influence velocity estimation when using
      nonuniformly sampled sequences. First, it is shown that long reverberation times
      lead to discontinuities in the signal from stationary clutter after each B-mode
      interruption. Second, using frequency analysis, it is shown that clutter
      filtering of nonuniformly sampled data may introduce artifacts in the velocity
      spectrum, and also lead to significant bias in mean velocity estimates. Methods
      are presented for quantification of these effects, and utilized to analyze three
      types of sparse duplex sequences for blood velocity estimation. In particular, it
      is argued that the use of such sequences in cardiac applications is not
      recommended because of long reverberation time. Additionally, it is found that
      the use of regression filters to filter nonuniformly sampled data may produce
      significant artifacts in pulsed wave Doppler spectra, but is less significant for
      color Doppler imaging applications. In vitro and in vivo examples are included
      showing the presence and magnitude of these problems in clinically relevant
      applications. 

PMID- 25965678
TI  - 4-D spatiotemporal analysis of ultrasound contrast agent dispersion for prostate
      cancer localization: a feasibility study.
AB  - Currently, nonradical treatment for prostate cancer is hampered by the lack of
      reliable diagnostics. Contrastultrasound dispersion imaging (CUDI) has recently
      shown great potential as a prostate cancer imaging technique. CUDI estimates the
      local dispersion of intravenously injected contrast agents, imaged by transrectal
      dynamic contrast-enhanced ultrasound (DCE-US), to detect angiogenic processes
      related to tumor growth. The best CUDI results have so far been obtained by
      similarity analysis of the contrast kinetics in neighboring pixels. To date, CUDI
      has been investigated in 2-D only. In this paper, an implementation of 3-D CUDI
      based on spatiotemporal similarity analysis of 4-D DCE-US is described. Different
      from 2-D methods, 3-D CUDI permits analysis of the entire prostate using a single
      injection of contrast agent. To perform 3-D CUDI, a new strategy was designed to
      estimate the similarity in the contrast kinetics at each voxel, and data
      processing steps were adjusted to the characteristics of 4-D DCE-US images. The
      technical feasibility of 4-D DCE-US in 3-D CUDI was assessed and confirmed.
      Additionally, in a preliminary validation in two patients, dispersion maps by 3-D
      CUDI were quantitatively compared with those by 2-D CUDI and with 12-core
      systematic biopsies with promising results. 

PMID- 25965679
TI  - Acoustic reciprocity of spatial coherence in ultrasound imaging.
AB  - A conventional ultrasound image is formed by transmitting a focused wave into
      tissue, time-shifting the backscattered echoes received on an array transducer,
      and summing the resulting signals. The van Cittert-Zernike theorem predicts a
      particular similarity, or coherence, of these focused signals across the
      receiving array. Many groups have used an estimate of the coherence to augment or
      replace the B-mode image in an effort to suppress noise and stationary clutter
      echo signals, but this measurement requires access to individual receive channel
      data. Most clinical systems have efficient pipelines for producing focused and
      summed RF data without any direct way to individually address the receive
      channels. We describe a method for performing coherence measurements that is more
      accessible for a wide range of coherence-based imaging. The reciprocity of the
      transmit and receive apertures in the context of coherence is derived and
      equivalence of the coherence function is validated experimentally using a
      research scanner. The proposed method is implemented on a commercial ultrasound
      system and in vivo short-lag spatial coherence imaging is demonstrated using only
      summed RF data. The components beyond the acquisition hardware and beamformer
      necessary to produce a real-time ultrasound coherence imaging system are
      discussed. 

PMID- 25965680
TI  - Software-based high-level synthesis design of FPGA beamformers for synthetic
      aperture imaging.
AB  - Field-programmable gate arrays (FPGAs) can potentially be configured as
      beamforming platforms for ultrasound imaging, but a long design time and skilled
      expertise in hardware programming are typically required. In this article, we
      present a novel approach to the efficient design of FPGA beamformers for
      synthetic aperture (SA) imaging via the use of software-based high-level
      synthesis techniques. Software kernels (coded in OpenCL) were first developed to
      stage-wise handle SA beamforming operations, and their corresponding FPGA logic
      circuitry was emulated through a high-level synthesis framework. After design
      space analysis, the fine-tuned OpenCL kernels were compiled into register
      transfer level descriptions to configure an FPGA as a beamformer module. The
      processing performance of this beamformer was assessed through a series of
      offline emulation experiments that sought to derive beamformed images from SA
      channel-domain raw data (40-MHz sampling rate, 12 bit resolution). With 128
      channels, our FPGA-based SA beamformer can achieve 41 frames per second (fps)
      processing throughput (3.44 * 10(8) pixels per second for frame size of 256 * 256
      pixels) at 31.5 W power consumption (1.30 fps/W power efficiency). It utilized
      86.9% of the FPGA fabric and operated at a 196.5 MHz clock frequency (after
      optimization). Based on these findings, we anticipate that FPGA and high-level
      synthesis can together foster rapid prototyping of real-time ultrasound processor
      modules at low power consumption budgets. 

PMID- 25965681
TI  - Performance evaluation of the spectral centroid downshift method for attenuation
      estimation.
AB  - Estimation of frequency-dependent ultrasonic attenuation is an important aspect
      of tissue characterization. Along with other acoustic parameters studied in
      quantitative ultrasound, the attenuation coefficient can be used to differentiate
      normal and pathological tissue. The spectral centroid downshift (CDS) method is
      one the most common frequencydomain approaches applied to this problem. In this
      study, a statistical analysis of this method's performance was carried out based
      on a parametric model of the signal power spectrum in the presence of electronic
      noise. The parametric model used for the power spectrum of received RF data
      assumes a Gaussian spectral profile for the transmit pulse, and incorporates
      effects of attenuation, windowing, and electronic noise. Spectral moments were
      calculated and used to estimate second-order centroid statistics. A theoretical
      expression for the variance of a maximum likelihood estimator of attenuation
      coefficient was derived in terms of the centroid statistics and other model
      parameters, such as transmit pulse center frequency and bandwidth, RF data window
      length, SNR, and number of regression points. Theoretically predicted estimation
      variances were compared with experimentally estimated variances on RF data sets
      from both computer-simulated and physical tissue-mimicking phantoms. Scan
      parameter ranges for this study were electronic SNR from 10 to 70 dB, transmit
      pulse standard deviation from 0.5 to 4.1 MHz, transmit pulse center frequency
      from 2 to 8 MHz, and data window length from 3 to 17 mm. Acceptable agreement was
      observed between theoretical predictions and experimentally estimated values with
      differences smaller than 0.05 dB/cm/MHz across the parameter ranges investigated.
      This model helps predict the best attenuation estimation variance achievable with
      the CDS method, in terms of said scan parameters. 

PMID- 25965682
TI  - Removal of residual cavitation nuclei to enhance histotripsy erosion of model
      urinary stones.
AB  - Histotripsy has been shown to be an effective treatment for model kidney stones,
      eroding their surface to tiny particulate debris via a cavitational bubble cloud.
      However, similar to shock wave lithotripsy, histotripsy stone treatments display
      a rate-dependent efficacy, with pulses applied at a low rate generating more
      efficient stone erosion in comparison with those applied at a high rate. This is
      hypothesized to be the result of residual cavitation bubble nuclei generated by
      bubble cloud collapse. Although the histotripsy bubble cloud only lasts on the
      order of 100 MUs, these microscopic remnant bubbles can persist on the order of 1
      s, inducing direct attenuation of subsequent histotripsy pulses and influencing
      bubble cloud dynamics. In an effort to mitigate these effects, we have developed
      a novel strategy to actively remove residual cavitation nuclei from the field
      using low-amplitude ultrasound pulses. Previous work has demonstrated that with
      selection of the appropriate acoustic parameters these bubble removal pulses can
      stimulate the aggregation and subsequent coalescence of microscopic bubble
      nuclei, effectively deleting them from the target volume. Here, we incorporate
      bubble removal pulses in histotripsy treatment of model kidney stones. It was
      found that when histotripsy is applied at low rate (1 Hz), bubble removal does
      not produce a statistically significant change in erosion. At higher pulse rates
      of 10, 100, and 500 Hz, incorporating bubble removal results in 3.7-, 7.5-, and
      2.7-fold increases in stone erosion, respectively. High-speed imaging indicates
      that the introduction of bubble removal pulses allows bubble cloud dynamics
      resulting from high pulse rates to more closely approximate those generated at
      the low rate of 1 Hz. These results corroborate previous work in the field of
      shock wave lithotripsy regarding the ill effects of residual bubble nuclei, and
      suggest that high treatment efficiency can be recovered at high pulse rates
      through appropriate manipulation of the cavitation environment surrounding the
      stone. 

PMID- 25965683
TI  - Multicarrier airborne ultrasound transmission with piezoelectric transducers.
AB  - In decentralized localization systems, the received signal has to be assigned to
      the sender. Therefore, longrange airborne ultrasound communication enables the
      transmission of an identifier of the sender within the ultrasound signal to the
      receiver. Further, in areas with high electromagnetic noise or electromagnetic
      free areas, ultrasound communication is an alternative. Using code division
      multiple access (CDMA) to transmit data is ineffective in rooms due to high echo
      amplitudes. Further, piezoelectric transducers generate a narrow-band ultrasound
      signal, which limits the data rate. This work shows the use of multiple carrier
      frequencies in orthogonal frequency division multiplex (OFDM) and differential
      quadrature phase shift keying modulation with narrowband piezoelectric devices to
      achieve a packet length of 2.1 ms. Moreover, the adapted channel coding increases
      data rate by correcting transmission errors. As a result, a 2-carrier ultrasound
      transmission system on an embedded system achieves a data rate of approximately
      5.7 kBaud. Within the presented work, a transmission range up to 18 m with a
      packet error rate (PER) of 13% at 10-V supply voltage is reported. In addition,
      the transmission works up to 22 m with a PER of 85%. Moreover, this paper shows
      the accuracy of the frame synchronization over the distance. Consequently, the
      system achieves a standard deviation of 14 MUs for ranges up to 10 m. 

PMID- 25965684
TI  - A model-based approach to crack sizing with ultrasonic arrays.
AB  - Ultrasonic phased array systems have become increasingly popular in the last 10
      years as tools for flaw detection and characterization within the nondestructive
      testing industry. The existence and location of flaws can often be deduced via
      images generated from the data captured by these arrays. A factor common to these
      imaging techniques is the subjective thresholding required to estimate the size
      of the flaw. This paper puts forward an objective approach which employs a
      mathematical model. By exploiting the relationship between the width of the
      central lobe of the scattering matrix and the crack size, an analytical
      expression for the crack length is reached via the Born approximation.
      Conclusions are then drawn on the minimum resolvable crack length of the method
      and it is thus shown that the formula holds for subwavelength defects. An
      analytical expression for the error that arises from the discrete nature of the
      array is then derived and it is observed that the method becomes less sensitive
      to the discretization of the array as the distance between the flaw and array
      increases. The methodology is then extended and tested on experimental data
      collected from welded austenitic plates containing a lack-of-fusion crack of 6 mm
      length. An objective sizing matrix (OSM) is produced by assessing the similarity
      between the scattering matrices arising from experimentally collected data with
      those arising from the Born approximation over a range of crack lengths and
      frequencies. Initially, the global minimum of the OSM is taken as the objective
      estimation of the crack size, giving a measurement of 7 mm. This is improved upon
      by the adoption of a multifrequency averaging approach, with which an improved
      crack size estimation of 6.4 mm is obtained. 

PMID- 25965685
TI  - Robust helical path separation for thickness mapping of pipes by guided wave
      tomography.
AB  - Pipe wall loss caused by corrosion can be quantified across an area by
      transmitting guided Lamb waves through the region and measuring the resulting
      signals. Typically the dispersive relationship for these waves, which means that
      wave velocity is a known function of thickness, is exploited, enabling the wall
      thickness to be determined from a velocity reconstruction. The accuracy and
      quality of this reconstruction is commonly limited by the angle of view available
      from the transducer arrays. These arrays are often attached as a pair of ring
      arrays on either side of the inspected region, and due to the cylindrical nature
      of the pipe, waves are able to travel in an infinite number of helical paths
      between any two transducers. The first arrivals can be separated relatively
      easily by time gating, but by using just these components the angle of view is
      severely restricted. To improve the viewing angle, it is necessary to separate
      the wavepackets. This paper provides an outline of a separation approach:
      initially the waves are backpropagated to their source to align the different
      signals, then a filtering technique is applied to select the desired components.
      The technique is applied to experimental data and demonstrated to robustly
      separate the signals. 

PMID- 25965686
TI  - Ultra-wideband ladder filter using SH(0) plate wave in thin LiNbO(3) plate and
      its application to tunable filter.
AB  - A cognitive radio terminal using vacant frequency bands of digital TV (DTV)
      channels, i.e., TV white space, strongly requires a compact tunable filter
      covering a wide frequency range of the DTV band (470 to 710 MHz in Japan). In
      this study, a T-type ladder filter using ultra-wideband shear horizontal mode
      plate wave resonators was fabricated, and a low peak insertion loss of 0.8 dB and
      an ultra-large 6 dB bandwidth of 240 MHz (41%) were measured in the DTV band. In
      addition, bandpass filters with different center frequencies of 502 and 653 MHz
      at 6 dB attenuation were numerically synthesized based on the same T-type ladder
      filter in conjunction with band rejection filters with different frequencies. The
      results suggest that the combination of the wideband T-type ladder filter and the
      band rejection filters connected with variable capacitors enables a tunable
      filter with large tunability of frequency and bandwidth as well as large
      rejection at the adjacent channels of an available TV white space. 

PMID- 25965687
TI  - A three-mask process for fabricating vacuum-sealed capacitive micromachined
      ultrasonic transducers using anodic bonding.
AB  - This paper introduces a simplified fabrication method for vacuum-sealed
      capacitive micromachined ultrasonic transducer (CMUT) arrays using anodic
      bonding. Anodic bonding provides the established advantages of wafer-bondingbased
      CMUT fabrication processes, including process simplicity, control over plate
      thickness and properties, high fill factor, and ability to implement large
      vibrating cells. In addition to these, compared with fusion bonding, anodic
      bonding can be performed at lower processing temperatures, i.e., 350 degrees C as
      opposed to 1100 degrees C; surface roughness requirement for anodic bonding is
      more than 10 times more relaxed, i.e., 5-nm rootmean- square (RMS) roughness as
      opposed to 0.5 nm for fusion bonding; anodic bonding can be performed on smaller
      contact area and hence improves the fill factor for CMUTs. Although anodic
      bonding has been previously used for CMUT fabrication, a CMUT with a vacuum
      cavity could not have been achieved, mainly because gas is trapped inside the
      cavities during anodic bonding. In the approach we present in this paper, the
      vacuum cavity is achieved by opening a channel in the plate structure to evacuate
      the trapped gas and subsequently sealing this channel by conformal silicon
      nitride deposition in the vacuum environment. The plate structure of the
      fabricated CMUT consists of the single-crystal silicon device layer of a silicon
      on-insulator wafer and a thin silicon nitride insulation layer. The presented
      fabrication approach employs only three photolithographic steps and combines the
      advantages of anodic bonding with the advantages of a patterned metal bottom
      electrode on an insulating substrate, specifically low parasitic series
      resistance and low parasitic shunt capacitance. In this paper, the developed
      fabrication scheme is described in detail, including process recipes. The
      fabricated transducers are characterized using electrical input impedance
      measurements in air and hydrophone measurements in immersion. A representative
      design is used to demonstrate immersion operation in conventional, collapse
      snapback, and collapse modes. In collapsemode operation, an output pressure of
      1.67 MPa pp is shown at 7 MHz on the surface of the transducer for 60-Vpp, 3
      cycle sinusoidal excitation at 30-V dc bias. 

PMID- 25965688
TI  - Absolute ultrasound perfusion parameter quantification of a tissue-mimicking
      phantom using bolus tracking [Correspondence].
AB  - This study presents three methods for absolute quantification in ultrasound
      perfusion analysis based on bolus tracking. The first two methods deconvolve the
      perfusion time sequence with a measured AIF, using a nonparametric or a
      parametric model of the tissue residue function, respectively. The third method
      is a simplified approach avoiding deconvolution by assuming a narrow AIF. A
      phantom with a dialyzer filter as a tissue-mimicking model was used for
      evaluation. Estimated mean transit times and blood volumes were compared with the
      theoretical values. A match with a maximum error of 12% was achieved. 

PMID- 25965690
TI  - Highly enantioselective and anti-diastereoselective catalytic intermolecular
      glyoxylate-ene reactions: effect of the geometrical isomers of alkenes.
AB  - An efficient method for the synthesis of homoallylic alcohols with high
      enantioselectivities and anti-diastereoselectivities via an In(III)-catalyzed
      intermolecular glyoxylate-ene reaction has been developed. The geometrical
      isomers of alkenes were shown to have different reactivities. Only the isomers of
      the alkenes having a proton beta-cis to the substituent reacted in this catalytic
      system. 

PMID- 25965691
TI  - Preliminary investigation of the possible association between arsenic levels in
      drinking water and suicide mortality.
AB  - BACKGROUND: Arsenic-contaminated drinking water (ACDW) represents a major global
      public health problem. A few previous studies suggested that consuming ACDW may
      be associated with elevated risk for depression. AIM: Since depression is the
      most relevant risk factor for suicide, we hypothesized that consumption of ACDW
      may be also associated with suicide. METHOD: To investigate this, we compared the
      age-standardized suicide rates (SSR) of 1639 Hungarian settlements with low
      (<=10MUg/l), intermediate (11-30MUg/l), high (31-50MUg/l) and very high
      (>=51MUg/l) levels of arsenic in drinking water. RESULT: We found a positive
      association between SSR and consumption of ACDW. LIMITATIONS: (1) we used
      aggregated (i.e., non-individual) data; (2) we have not adjusted our model for
      important medical and socio-demographic determinants of suicidal behavior; (3) we
      had no data on differences in bottled water consumption between settlements.
      CONCLUSIONS: Our results indicate that in addition to its well-known adverse
      health effects, consumption of ACDW may also be associated with suicidal
      behavior.

PMID- 25965692
TI  - The association between depression and emotional and social loneliness in older
      persons and the influence of social support, cognitive functioning and
      personality: A cross-sectional study.
AB  - BACKGROUND: We investigated the association between old age depression and
      emotional and social loneliness. METHODS: A cross-sectional study was performed
      using data from the Netherlands Study of Depression in Older Persons (NESDO). A
      total of 341 participants diagnosed with a depressive disorder, and 125 non
      depressed participants were included. Depression diagnosis was confirmed with the
      Composite International Diagnostic Interview. Emotional and social loneliness
      were assessed using the De Jong Gierveld Loneliness Scale. Socio-demographic
      variables, social support variables, depression characteristics (Inventory of
      Depressive Symptoms), cognitive functioning (Mini Mental State Examination) and
      personality factors (the NEO- Five Factor Inventory and the Pearlin Mastery
      Scale) were considered as possible explanatory factors or confounders. (Multiple)
      logistic regression analyses were performed. RESULTS: Depression was strongly
      associated with emotional loneliness, but not with social loneliness. A higher
      sense of neuroticism and lower sense of mastery were the most important
      explanatory factors. Also, we found several other explanatory and confounding
      factors in the association of depression and emotional loneliness; a lower sense
      of extraversion and higher severity of depression. LIMITATIONS: We performed a
      cross-sectional observational study. Therefore we cannot add evidence in regard
      to causation; whether depression leads to loneliness or vice versa. CONCLUSIONS:
      Depression in older persons is strongly associated with emotional loneliness but
      not with social loneliness. Several personality traits and the severity of
      depression are important in regard to the association of depression and emotional
      loneliness. It is important to develop interventions in which both can be
      treated.

PMID- 25965693
TI  - Longitudinal symptom course in adults with recurrent depression: Impact on
      impairment and risk of psychopathology in offspring.
AB  - BACKGROUND: Major depressive disorder (MDD) is common and is associated with an
      increased risk of psychopathology in offspring. However, depression shows
      considerable heterogeneity in its course over time. The aim of this study is to
      examine the relationship between parent depression symptom trajectories and (i)
      quality of life and social impairment and (ii) psychiatric disorder and
      depression symptoms in their offspring. METHOD: Participants were from a
      longitudinal study of 337 parents with recurrent MDD and their adolescent
      offspring. Families were assessed on three occasions over four years. Parent
      depressive symptoms and current MDD diagnosis were assessed using the Schedules
      for Clinical Assessment in Neuropsychiatry. Adult quality of life and social
      impairment were derived from the EuroQol and current employment status.
      Psychiatric outcomes in offspring were assessed using the Child and Adolescent
      Psychiatric Assessment. RESULTS: Using latent class growth analysis, three
      distinct classes of parental depression symptoms were identified (asymptomatic,
      mild, and chronic high). Parent depression classes were associated with their own
      quality of life and social impairment, and with psychiatric disorder and
      depression symptoms in their offspring. LIMITATIONS: (i) We were unable to test
      associations with specific offspring disorders, (ii) we did not address the
      direction of effects underlying associations, and (iii) the sample consisted
      primarily of mothers and findings may not generalise to depressed fathers.
      CONCLUSION: Longitudinal assessments of depressive symptoms in parents could help
      to identify families who are most in need of early intervention.

PMID- 25965694
TI  - Mechanistic Basis for Regioselection and Regiodivergence in Nickel-Catalyzed
      Reductive Couplings.
AB  - The control of regiochemistry is a considerable challenge in the development of a
      wide array of catalytic processes. Simple pi-components such as alkenes, alkynes,
      1,3-dienes, and allenes are among the many classes of substrates that present
      complexities in regioselective catalysis. Considering an internal alkyne as a
      representative example, when steric and electronic differences between the two
      substituents are minimal, differentiating among the two termini of the alkyne
      presents a great challenge. In cases where the differences between the alkyne
      substituents are substantial, overcoming those biases to access the regioisomer
      opposite that favored by substrate biases often presents an even greater
      challenge. Nickel-catalyzed reductive couplings of unsymmetrical pi-components
      make up a group of reactions where control of regiochemistry presents a
      challenging but important objective. In the course of our studies of aldehyde
      alkyne reductive couplings, complementary solutions to challenges in regiocontrol
      have been developed. Through careful selection of the ligand and reductant, as
      well as the more subtle reaction variables such as temperature and concentration,
      effective protocols have been established that allow highly selective access to
      either regiosiomer of the allylic alcohol products using a wide range of
      unsymmetrical alkynes. Computational studies and an evaluation of reaction
      kinetics have provided an understanding of the origin of the regioselectivity
      control. Throughout the various procedures described, the development of ligand
      substrate interactions plays an essential role, and the overall kinetic
      descriptions were found to differ between protocols. Rational alteration of the
      rate-determining step plays a key role in the regiochemistry reversal strategy,
      and in one instance, the two possible regioisomeric outcomes in a single reaction
      were found to operate by different kinetic descriptions. With this mechanistic
      information in hand, the empirical factors that influence regiochemistry can be
      readily understood, and more importantly, the insights suggest simple and
      predictable experimental variables to achieving a desired reaction outcome. These
      studies thus present a detailed picture of the influences that control
      regioselectivity in a specific catalytic reaction, but they also delineate
      strategies for regiocontrol that may extend to numerous classes of reactions. The
      work provides an illustration of how insights into the kinetics and mechanism of
      a catalytic process can rationalize subtle empirical findings and suggest simple
      and rational modifications in procedure to access a desirable reaction outcome.
      Furthermore, these studies present an illustration of how important challenges in
      organic synthesis can be met by novel reactivity afforded by base metal
      catalysis. The use of nickel catalysis in this instance not only provides an
      inexpensive and sustainable method for catalysis but also enables unique
      reactivity patterns not accessible to other metals. 

PMID- 25965696
TI  - [Not Available].

PMID- 25965695
TI  - Resveratrol ameliorates imiquimod-induced psoriasis-like skin inflammation in
      mice.
AB  - BACKGROUND: The polyphenol resveratrol has anti-inflammatory effects in various
      cells, tissues, animals and human settings of low-grade inflammation. Psoriasis
      is a disease of both localized and systemic low-grade inflammation. The Sirtuin1
      enzyme thought to mediate the effects of resveratrol is present in skin and
      resveratrol is known to down regulate NF-kappaB; an important contributor in the
      development of psoriasis. Consequently we investigated whether resveratrol has an
      effect on an Imiquimod induced psoriasis-like skin inflammation in mice and
      sought to identify candidate genes, pathways and interleukins mediating the
      effects. METHODS: The study consisted of three treatment groups: A control group,
      an Imiquimod group and an Imiquimod+resveratrol group. Psoriasis severity was
      assessed using elements of the Psoriasis Area Severity Index, skin thickness
      measurements, and histological examination. We performed an RNA microarray from
      lesional skin and afterwards Ingenuity pathway analysis to identify affected
      signalling pathways. Our microarray was compared to a previously deposited
      microarray to determine if gene changes were psoriasis-like, and to a human
      microarray to determine if findings could be relevant in a human setting.
      RESULTS: Imiquimod treatment induced a psoriasis-like skin inflammation.
      Resveratrol significantly diminished the severity of the psoriasis-like skin
      inflammation. The RNA microarray revealed a psoriasis-like gene expression
      profile in the Imiquimod treated group, and highlighted several resveratrol
      dependent changes in relevant genes, such as increased expression of genes
      associated with retinoic acid stimulation and reduced expression of genes
      involved in IL-17 dependent pathways. Quantitative PCR confirmed a resveratrol
      dependent decrease in mRNA levels of IL-17A and IL-19; both central in developing
      psoriasis. CONCLUSIONS: Resveratrol ameliorates psoriasis, and changes expression
      of retinoic acid stimulated genes, IL-17 signalling pathways, IL-17A and IL-19
      mRNA levels in a beneficial manner, which suggests resveratrol, might have a role
      in the treatment of psoriasis and should be explored further in a human setting.

PMID- 25965697
TI  - Reversed Electron Apportionment in Mesolytic Cleavage: The Reduction of Benzyl
      Halides by SmI2.
AB  - The paradigm that the cleavage of the radical anion of benzyl halides occurs in
      such a way that the negative charge ends up on the departing halide leaving
      behind a benzyl radical is well rooted in chemistry. By studying the kinetics of
      the reaction of substituted benzylbromides and chlorides with SmI2 in THF it was
      found that substrates para-substituted with electron-withdrawing groups (CN and
      CO2 Me), which are capable of forming hydrogen bonds with a proton donor and
      coordinating to samarium cation, react in a reversed electron apportionment mode.
      Namely, the halide departs as a radical. This conclusion is based on the found
      convex Hammett plots, element effects, proton donor effects, and the effect of
      tosylate (OTs) as a leaving group. The latter does not tend to tolerate radical
      character on the oxygen atom. In the presence of a proton donor, the tolyl
      derivatives were the sole product, whereas in its absence, the coupling dimer was
      obtained by a SN 2 reaction of the benzyl anion on the neutral substrate. The
      data also suggest that for the para-CN and CO2 Me derivatives in the presence of
      a proton donor, the first electron transfer is coupled with the proton transfer. 

PMID- 25965698
TI  - Nanoradioliposomes molecularly modulated to study the lung deep lymphatics
      drainage.

PMID- 25965699
TI  - Editorial.

PMID- 25965700
TI  - Benchmarking Controlled Trial--a novel concept covering all observational
      effectiveness studies.
AB  - The Benchmarking Controlled Trial (BCT) is a novel concept which covers all
      observational studies aiming to assess effectiveness. BCTs provide evidence of
      the comparative effectiveness between health service providers, and of
      effectiveness due to particular features of the health and social care systems.
      BCTs complement randomized controlled trials (RCTs) as the sources of evidence on
      effectiveness. This paper presents a definition of the BCT; compares the position
      of BCTs in assessing effectiveness with that of RCTs; presents a checklist for
      assessing methodological validity of a BCT; and pilot-tests the checklist with
      BCTs published recently in the leading medical journals. 

PMID- 25965702
TI  - Atypical exanthems associated with Parvovirus B19 (B19V) infection in children
      and adults.
AB  - Parvovirus B19 (B19V) infection may differently manifest in various age groups.
      Erythema infectiosum ('fifth disease') is the most common B19V manifestations in
      children. Arthralgias and arthritis, with or without rash, are common
      manifestations of B19V infection in adults. Pruritus is usually present in adults
      and children. However, other cutaneous manifestations and atypical exanthems have
      been occasionally reported during B19V infection. To investigate the putative
      role of B19V infection in atypical exanthems, a total of 390 consecutive patients
      with atypical exanthems were analysed for B19V infection by determining B19V IgG
      and IgM antibodies titres in acute and convalescent phase as well as B19V DNA
      detection in serum by polymerase chain reaction (PCR). Atypical exanthems
      resulted related to B19V infection in 6 of the 120 pediatric (5%) and 14 of the
      270 adult patients (5.2%). In conclusion this study reveals that atypical
      exanthems related to B19V infection are possible both in children and in adults,
      with a similar prevalence.

PMID- 25965701
TI  - Genotype-Associated Differential NKG2D Expression on CD56+CD3+ Lymphocytes
      Predicts Response to Pegylated-Interferon/Ribavirin Therapy in Chronic Hepatitis
      C.
AB  - Hepatitis C virus (HCV) genotype 1 infections are significantly more difficult to
      eradicate with PEG-IFN/ribavirin therapy, compared to HCV genotype 2. The aim of
      this work is to investigate the difference of immunological impairments
      underlying this phenomenon. Pre-treatment NKG2D expression on peripheral
      CD56+CD3+ lymphocytes and CD56+CD3- NK cells from cases of chronic hepatitis C
      were analyzed and assessed by treatment effect. Two strains of HCV were used to
      co-incubate with immune cells in vitro. NKG2D expression on peripheral CD56+CD3+
      lymphocytes, but not NK cells, was significantly impaired in genotype 1
      infection, compared to genotype 2. When peripheral blood mononuclear cells from
      healthy donors were co-incubated with TNS2J1, a genotype 1b/2a chimera strain, or
      with JFH1, a genotype 2a strain, genotype-specific decrease of NKG2D on CD56+CD3+
      lymphocytes, but not NK cells, was observed. Pre-treatment NKG2D expression on
      peripheral CD56+CD3+ lymphocytes significantly correlated with reduction in serum
      HCV RNA levels from week 0 to week 4, and predicted treatment response. Ex vivo
      stimulation of peripheral CD56+CD3+ lymphocytes showed NKG2D expression
      correlated IFN-gamma production. In conclusion, Decreased NKG2D expression on
      CD56+CD3+ lymphocytes in chronic HCV genotype 1 infection predicts inferior
      treatment response to PEG-IFN/ribavirin therapy compared to genotype 2. 

PMID- 25965703
TI  - Radiative heat transfer in 2D Dirac materials.
AB  - We compute the radiative heat transfer between two sheets of 2D Dirac materials,
      including topological Chern insulators and graphene, within the framework of the
      local approximation for the optical response of these materials. In this
      approximation, which neglects spatial dispersion, we derive both numerically and
      analytically the short-distance asymptotic of the near-field heat transfer in
      these systems, and show that it scales as the inverse of the distance between the
      two sheets. Finally, we discuss the limitations to the validity of this scaling
      law imposed by spatial dispersion in 2D Dirac materials. 

PMID- 25965704
TI  - The effect of mustard gas on salivary trace metals (Zn, Mn, Cu, Mg, Mo, Sr, Cd,
      Ca, Pb, Rb).
AB  - We have determined and compared trace metals concentration in saliva taken from
      chemical warfare injures who were under the exposure of mustard gas and healthy
      subjects by means of inductively coupled plasma optical emission spectroscopy
      (ICP-OES) for the first time. The influence of preliminary operations on the
      accuracy of ICP-OES analysis, blood contamination, the number of restored teeth
      in the mouth, salivary flow rate, and daily variations in trace metals
      concentration in saliva were also considered. Unstimulated saliva was collected
      at 10:00-11:00 a.m. from 45 subjects in three equal groups. The first group was
      composed of 15 healthy subjects (group 1); the second group consisted of 15
      subjects who, upon chemical warfare injuries, did not use Salbutamol spray, which
      they would have normally used on a regular basis (group 2); and the third group
      contained the same number of patients as the second group, but they had taken
      their regular medicine (Salbutamol spray; group 3). Our results showed that the
      concentration of Cu in saliva was significantly increased in the chemical warfare
      injures compared to healthy subjects, as follows: healthy subjects 15.3+/- 5.45
      (p.p.b.), patients (group 2) 45.77+/-13.65, and patients (Salbutamol spray; group
      3) 29 +/-8.51 (P <0.02). In contrast, zinc was significantly decreased in the
      patients, as follows: healthy subjects 37 +/- 9.03 (p.p.b.), patients (group 2)
      12.2 +/- 3.56, and patients (Salbutamol spray; group 3) 20.6 +/-10.01 (P < 0.01).
      It is important to note that direct dilution of saliva samples with ultrapure
      nitric acid showed the optimum ICP-OES outputs.

PMID- 25965705
TI  - Obstructive sleep apnea and atrial fibrillation progression. Another reason to
      wear continuous positive airway pressure?

PMID- 25965706
TI  - A prospective evaluation of edoxaban compared to warfarin in subjects undergoing
      cardioversion of atrial fibrillation: The EdoxabaN vs. warfarin in subjectS
      UndeRgoing cardiovErsion of Atrial Fibrillation (ENSURE-AF) study.
AB  - We designed a prospective, randomized, open-label, blinded end point evaluation
      parallel group Phase 3b clinical trial comparing edoxaban (a new oral factor Xa
      inhibitor) with enoxaparin/warfarin followed by warfarin alone in subjects
      undergoing planned electrical cardioversion of non-valvular atrial fibrillation.
      The primary efficacy end point is the composite end points of stroke, systemic
      embolic event, myocardial infarction, and cardiovascular (CV) mortality, from
      randomization until the end of follow-up (day 56 post cardioversion). The primary
      safety end point is the composite of major and clinically-relevant non-major
      bleeding, from the first administration of study drug to end of treatment (Day 28
      post cardioversion) +3 days. The primary efficacy analysis will be conducted on
      the intention-to-treat population whereas the primary safety analysis, on the
      safety population. The study includes stratification on the following levels: (i)
      approach to cardioversion (transoesophagel echocardiography or non
      transoesophagel echocardiography) as determined by the Investigator; (ii)
      subject's experience in taking anticoagulants at the time of randomization
      (anticoagulant-experienced or anticoagulant-naive); and (iii) assigned edoxaban
      dose (full 60 mg QD or reduced 30 mg dose QD). A subject with one or more factors
      (CrCl >=15 mL/min and <=50 mL/min, low body weight [<=60 kg], and concomitant use
      of p-pg inhibitors (excluding amiodarone) will receive a reduced dose (30 mg) of
      edoxaban if the subject is randomized to the edoxaban group. ENSURE-AF will be
      the largest prospective randomised trial of anticoagulation for cardioversion,
      also involving a Non-VKA Oral Anticoagulant-edoxaban.

PMID- 25965707
TI  - Design and rationale of a prospective, collaborative meta-analysis of all
      randomized controlled trials of angiotensin receptor antagonists in Marfan
      syndrome, based on individual patient data: A report from the Marfan Treatment
      Trialists' Collaboration.
AB  - RATIONALE: A number of randomized trials are underway, which will address the
      effects of angiotensin receptor blockers (ARBs) on aortic root enlargement and a
      range of other end points in patients with Marfan syndrome. If individual
      participant data from these trials were to be combined, a meta-analysis of the
      resulting data, totaling approximately 2,300 patients, would allow estimation
      across a number of trials of the treatment effects both of ARB therapy and of
      beta-blockade. Such an analysis would also allow estimation of treatment effects
      in particular subgroups of patients on a range of end points of interest and
      would allow a more powerful estimate of the effects of these treatments on a
      composite end point of several clinical outcomes than would be available from any
      individual trial. DESIGN: A prospective, collaborative meta-analysis based on
      individual patient data from all randomized trials in Marfan syndrome of (i) ARBs
      versus placebo (or open-label control) and (ii) ARBs versus beta-blockers will be
      performed. A prospective study design, in which the principal hypotheses, trial
      eligibility criteria, analyses, and methods are specified in advance of the
      unblinding of the component trials, will help to limit bias owing to data
      dependent emphasis on the results of particular trials. The use of individual
      patient data will allow for analysis of the effects of ARBs in particular patient
      subgroups and for time-to-event analysis for clinical outcomes. The meta-analysis
      protocol summarized in this report was written on behalf of the Marfan Treatment
      Trialists' Collaboration and finalized in late 2012, without foreknowledge of the
      results of any component trial, and will be made available online
      (http://www.ctsu.ox.ac.uk/research/meta-trials).

PMID- 25965708
TI  - The Third DANish Study of Optimal Acute Treatment of Patients with ST-segment
      Elevation Myocardial Infarction: Ischemic postconditioning or deferred stent
      implantation versus conventional primary angioplasty and complete
      revascularization versus treatment of culprit lesion only: Rationale and design
      of the DANAMI 3 trial program.
AB  - BACKGROUND: In patients undergoing primary percutaneous coronary intervention for
      ST-segment elevation myocardial infarction, ischemic postconditioning has been
      shown to reduce infarct size, but the effect on clinical outcome has not been
      tested in a large randomized trial. In addition, deferring stent implantation in
      the infarct-related lesion 1 to 3 days after acute opening of the infarct-related
      artery could have protective effects, by reducing the risk of injury caused by
      distal embolization and microvascular obstruction. Finally, a considerable
      fraction of patients present with lesions in other coronary artery branches than
      the infarct-related artery. Whether a strategy of complete or partial
      revascularization of these patients should be preferred remains uncertain. STUDY
      DESIGN: The DANAMI 3 trial program was designed to investigate 3 different
      randomized treatment strategies in patients with ST-segment elevation myocardial
      infarction: (1) ischemic postconditioning versus conventional treatment with a
      primary end point of death and hospitalization for heart failure; (2) deferring
      stent implantation in the infarct-related lesion versus conventional treatment
      with a primary end point of death, hospitalization for heart failure,
      reinfarction, and repeat revascularization; and (3) treatment of the culprit
      lesion only versus fractional flow reserve-guided complete revascularization in
      patients with multivessel disease, with a primary end point of death,
      reinfarction, and repeat revascularization. SUMMARY: The DANAMI 3 trial program
      will determine whether either of 2 approaches to reduce reperfusion injury and
      distal microvascular obstruction with postconditioning or deferred stent
      implantation will translate into improved clinical outcome and whether patients
      with multivessel disease undergoing primary percutaneous coronary intervention
      will benefit from a strategy of complete or partial revascularization.

PMID- 25965709
TI  - Rationale and design of the LosmApimod To Inhibit p38 MAP kinase as a TherapeUtic
      target and moDify outcomes after an acute coronary syndromE trial.
AB  - BACKGROUND: p38 mitogen-activated protein kinase (MAPK) mediates cytokine
      production and amplification of the inflammatory cascade. Through inhibition of
      p38 MAPK, losmapimod appears to attenuate the inflammatory response in the
      vascular wall and thus may help stabilize plaques. STUDY DESIGN: The LATITUDE
      TIMI 60 trial is a randomized, double-blind, placebo-controlled, parallel-group,
      multicenter study planned to be conducted in a 3-stage design. Overall, the trial
      is designed to include 25,500 patients hospitalized with non-ST-elevation or ST
      elevation myocardial infarction (MI) randomized to oral losmapimod (7.5 mg twice
      daily) versus matching placebo. Part A consists of a leading cohort (n = 3,500)
      that will provide an initial assessment of safety and exploratory efficacy before
      progressing to part B. Part B (n = ~22,000) of the study is event driven and will
      provide the primary assessment of efficacy. An independent safety review will be
      conducted after 3,500 patients in part B1 to determine whether a more focused
      schedule of clinic visits and laboratory assessments can be implemented (part
      B2). All patients are to be treated with study drug until week 12 and followed up
      until week 24. The primary end point is the composite of cardiovascular death,
      MI, or severe recurrent ischemia requiring urgent coronary revascularization. The
      key secondary end point is the composite of cardiovascular death or MI. The trial
      is designed to provide >=90% power for the primary end point. CONCLUSIONS: The
      LATITUDE-TIMI 60 trial will determine the efficacy and safety of short-term p38
      MAPK inhibition with losmapimod in acute MI. The trial design adopts a stepwise
      approach to decision making and collection of data.

PMID- 25965711
TI  - Long-term effects of ischemic postconditioning on clinical outcomes: 1-year
      follow-up of the POST randomized trial.
AB  - BACKGROUND: In the Effects of Postconditioning on Myocardial Reperfusion in
      Patients with ST-segment Elevation Myocardial Infarction (POST) trial, ischemic
      postconditioning failed to improve myocardial reperfusion. However, long-term
      effects of ischemic postconditioning on clinical outcomes are not known in
      patients with ST-segment elevation myocardial infarction. METHODS: A total of 700
      patients undergoing primary percutaneous coronary intervention (PCI) were
      randomly assigned to the postconditioning group or the conventional primary PCI
      group in a 1:1 ratio. Postconditioning was performed immediately after
      restoration of coronary flow by balloon occlusion 4 times for 1 minute. Complete
      follow-up data for major clinical events at 1 year were available in 695 patients
      (99.3%), and analyses were done by the intention to treat principle. The primary
      outcome was a composite of death, myocardial infarction, severe heart failure, or
      stent thrombosis at 1 year. RESULTS: At 1 year, a composite of death, myocardial
      infarction, severe heart failure, or stent thrombosis occurred in 21 patients
      (6.1%) in the postconditioning group and 16 patients (4.6%) in the conventional
      PCI group (hazard ratio [HR] 1.32, 95% CI 0.69-2.53, P = .40). The risk of death
      (4.9% vs 3.7%, HR 1.32, 95% CI 0.64-2.71, P = .46), heart failure (2.6% vs 2.3%,
      HR 1.13, 95% CI 0.44-2.94, P = .80), and stent thrombosis (2.3% vs 1.7%, HR 1.34,
      95% CI 0.46-3.85, P = .59) did not differ significantly between the 2 groups.
      CONCLUSIONS: Ischemic postconditioning does not seem to improve the 1-year
      clinical outcomes in patients with ST-segment elevation myocardial infarction
      undergoing primary PCI.

PMID- 25965712
TI  - Impact of obstructive sleep apnea and continuous positive airway pressure therapy
      on outcomes in patients with atrial fibrillation-Results from the Outcomes
      Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF).
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is common in patients with atrial
      fibrillation (AF). Little is known about the impact of OSA on AF treatment and
      long-term outcomes. We studied whether patients with OSA have a greater
      likelihood of progressing to more persistent forms of AF or require more
      hospitalizations and/or worse outcomes compared with patients without OSA.
      METHODS: A total of 10,132 patients were enrolled between June 2010 and August
      2011 in the Outcomes Registry for Better Informed Treatment of Atrial
      Fibrillation (ORBIT-AF) and followed for up to 2 years. The prevalence of OSA and
      continuous positive airway pressure (CPAP) treatment was captured at baseline.
      The association between OSA and major cardiovascular outcomes was analyzed using
      multivariable hierarchical logistic regression modeling and Cox frailty
      regression model. RESULTS: Of the 10,132 patients with AF, 1,841 had OSA.
      Patients with OSA were more symptomatic (22% vs 16% severe/disabling symptoms; P
      < .0001) and more often on rhythm control therapy (35% vs 31%; P = .0037). In
      adjusted analyses, patients with OSA had higher risk of hospitalization (hazard
      ratio [HR], 1.12; 95% CI, 1.03-1.22; P = .0078), but no difference in the risks
      of death (HR, 0.94; 95% CI, 0.77-1.15; P = .54); the composite of CV death,
      myocardial infarction, and stroke/transient ischemic attack (HR, 1.07; 95% CI,
      0.85-1.34; P = .57); major bleeding (HR, 1.18; 95% CI, 0.96-1.46; P = .11); or AF
      progression (HR, 1.06; 95% CI, 0.89-1.28; P = .51). Patients with OSA on CPAP
      treatment were less likely to progress to more permanent forms of AF compared
      with patients without CPAP (HR, 0.66; 95% CI, 0.46-0.94; P = .021). CONCLUSION:
      Compared with those without, AF patients with OSA have worse symptoms and higher
      risks of hospitalization, but similar mortality, major adverse cardiovascular
      outcome, and AF progression rates. CLINICAL TRIAL REGISTRATION: NCT01165710
      (http://www.clinicaltrials.gov).

PMID- 25965713
TI  - Impact of weight reduction on pericardial adipose tissue and cardiac structure in
      patients with atrial fibrillation.
AB  - BACKGROUND: Obesity and pericardial adipose tissue are independent risk factors
      for atrial fibrillation (AF) and adverse cardiac structural remodeling. The
      effect of weight reduction on pericardial adipose tissue and cardiac structure
      remains unknown. METHODS: We prospectively performed cardiac magnetic resonance
      imaging on 87 participants with AF undergoing either structured weight management
      (intervention) or general lifestyle advice (control). We measured pericardial
      adipose tissue, atrial and ventricular volumes, and myocardial mass at baseline
      and 12 months. RESULTS: In total, 69 participants underwent baseline and 12-month
      follow-up cardiac magnetic resonance imaging (intervention n = 36 and controls n
      = 33). From baseline to 12 months, weight loss (kg, mean [95% CI]) was greater in
      the intervention group from 101.5 kg (97.2-105.8 kg) to 86.5 kg (81.2-91.9 kg) as
      compared with controls from 102.6 kg (97.2-108.1 kg) to 98.7 kg (91.0-106.3 kg)
      (time-group interaction P < .001). The intervention group showed a reduction in
      left atrial volumes (mL) from 105.0 mL (98.9-111.1 mL) to 96.4 mL (91.6-101.1
      mL), whereas the change in the control group was from 108.8 mL (99.6-117.9 mL) to
      108.9 mL (99.8-118.0 mL) (time-group interaction P < .001). There was a decline
      in pericardial adipose tissue (cm(3)) from 140.9 cm(3) (129.3-152.4 cm(3)) to
      118.8 cm(3) (108.1-129.6 cm(3)) and myocardial mass (g) from 137.6 g (128.1-147.2
      g) to 123.1 g (114.5-131.7 g) in the intervention group, whereas the change in
      the control group was from 143.2 cm(3) (124.6-161.7 cm(3)) to 147.2 cm(3) (128.9
      165.4 cm(3)) for pericardial adipose tissue and 138.3 g (124.8-151.8 g) to 140.7
      g (127.4-154.1 g) for myocardial mass (both variables, time-group interaction P <
      .001). CONCLUSIONS: Weight reduction results in favorable structural remodeling
      and a reduction in pericardial adipose tissue burden.

PMID- 25965714
TI  - Accuracy of intravascular ultrasound and optical coherence tomography in
      identifying functionally significant coronary stenosis according to vessel
      diameter: A meta-analysis of 2,581 patients and 2,807 lesions.
AB  - INTRODUCTION: Accuracy of intracoronary imaging to discriminate functionally
      significant coronary stenosis according to vessel diameter remains to be defined.
      METHODS: PubMed, Scopus, and Google Scholar were systematically searched for
      studies assessing diagnostic accuracy (area under the receiver operating
      characteristic curve [AUC], the primary end point) and sensitivity and
      specificity (the secondary end points) of minimal luminal area (MLA) or of
      minimal luminal diameter (MLD) derived from intravascular ultrasound (IVUS) or
      optical coherence tomography (OCT) to detect functionally significant stenosis as
      determined with fractional flow reserve (FFR). RESULTS: Fifteen studies were
      included, 2 with 110 patients analyzing only left main (LM), 5 with 224 patients
      and 306 lesions using OCT, and 9 with 1532 patients and 1681 lesions with IVUS.
      Median MLA for the OCT studies was 1.96 mm(2) (1.85-1.98 mm(2)), 2.9 mm(2) (2.7
      3.1 mm(2)) for MLA of all lesions assessed with IVUS, 2.8 mm(2) (2.7-2.9 mm(2))
      for lesions with an angiographic diameter >3 mm, 2.4 mm(2) (2.4-2.5 mm(2)) for
      lesions <3 mm, and 5.4 mm(2) (5.1-5.6 mm(2)) for LM lesions. For OCT-MLA, AUC was
      0.80 (0.74-0.86), with a sensitivity of 0.81 (0.74-0.87) and specificity of 0.77
      (0.71-0.83), whereas OCT-MLD had an AUC of 0.85 (0.79-0.91), sensitivity of 0.74
      (0.69-0.78), and specificity of 0.70 (0.68-0.73). For IVUS-MLA, AUC was 0.78
      (0.75-0.81) for all lesions, 0.78 (0.73-0.84) for vessels with a diameter >3 mm,
      and 0.79 (0.70-0.89) for those with a diameter <3 mm. Left main AUC was 0.97
      (0.93-1). CONCLUSION: Intravascular ultrasound and OCT had modest diagnostic
      accuracy for identification hemodynamically significant lesions, also with
      specific cutoff for different diameters. Invasive imaging for assessment of LM
      severity demonstrated excellent correlation with FFR. What is already known about
      this subject? Fractional flow reserve represents the criterion standard to
      evaluate the prognostic value of coronary stenosis, whereas its relationship with
      IVUS and OCT remains to be assessed. What does this study add? Despite
      improvement, IVUS and OCT do not predict functional stenosis, even with dedicated
      cutoff, apart from LM disease. How might this impact on clinical practice? The
      recent guidelines of myocardial revascularization have stressed the crucial role
      of FFR before performing percutaneous coronary intervention on LM, whereas
      intravascular imaging is often exploited to drive revascularization. The present
      analysis stresses the point that LM percutaneous coronary intervention may be
      driven only by intravascular imaging, given the high accuracy for significant
      ischemic lesions, whereas for other vessels, these 2 techniques mirror 2
      different aspects.

PMID- 25965715
TI  - Analytical validation of novel cardiac biomarkers used in clinical trials.
AB  - BACKGROUND: Blood-based biomarkers such as cardiac troponin and B-natriuretic
      peptides are widely used in clinical practice for the diagnosis, rule out, and
      risk stratification for patients with acute coronary syndromes and heart failure.
      Because neither these nor any other laboratory test meets all clinical needs,
      there are many novel biomarkers that are proposed and evaluated each year for
      possible implementation into clinical practice. Results of clinical trials are
      used as a means to validate their effectiveness and to obtain regulatory
      approval. METHODS AND RESULTS: Novel biomarkers are discovered through a targeted
      approach using knowledge of the pathophysiology disease process and an untargeted
      approach where proteins from tissues or blood of disease patients are compared
      against healthy subjects or those with benign conditions. Once a candidate
      biomarker has been identified, it is important to understand where the protein is
      located and how it is released into blood. In designing trials, the requirements
      for Food and Drug Administration clearance and approval should be taken into
      consideration. There are preanalytical studies that should be considered
      including the preservative used to collect samples and in vivo and in vitro
      analyte stability. If the analyte is not stable, a surrogate marker could be used
      such as stable "pro" molecules (precursor proteins) may be preferred. Assay
      imprecision and bias, biological variation and criteria for the establishment of
      a reference range are important analytical attributes. The need for harmonization
      and commutability and correlation of results to other markers and clinical
      outcomes are important postanalytical attributes of novel biomarkers.
      CONCLUSIONS: Inadequate adherence to these variables when conducting clinical
      trials reduces the quality and value of the information contained in literature
      reports of novel serum/plasma-based biomarkers.

PMID- 25965716
TI  - Predictors of long-term outcomes in patients with hypertrophic cardiomyopathy
      undergoing cardiopulmonary stress testing and echocardiography.
AB  - BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) have exercise
      intolerance due to left ventricular outflow tract (LVOT) obstruction, mitral
      regurgitation, and left ventricular dysfunction. We sought to study predictors of
      outcomes in HCM patients undergoing cardiopulmonary stress testing (CPT).
      METHODS: We studied 1,005 HCM patients (50 +/- 14 years, 64% men, 77% on beta
      blockers) who underwent CPT with echocardiography. Clinical, echocardiographic,
      and exercise variables (peak oxygen consumption [VO2] and heart rate recovery
      [HRR] at first minute postexercise) were recorded. End point was a composite of
      death, appropriate defibrillator discharges, resuscitated sudden death, stroke,
      and heart failure admission. RESULTS: Mean left ventricular ejection fraction
      (LVEF), postexercise LVOT gradient, and peak VO2 were 62% +/- 6%, 92 +/- 51 mm
      Hg, and 21 +/- 6 mL kg(-1) min(-1), respectively. Despite 789 patients (78%)
      being in New York Heart Association classes I to II, only 8% achieved >100% age
      gender predicted peak VO2, whereas 77% and 15% achieved 50% to 100% and <50%,
      respectively. Left ventricular outflow tract gradient >=30 mm Hg was observed in
      83% patients, whereas 23% had abnormal HRR. More than 5.5 +/- 4 years, there were
      94 (9%) events; 511 (50%) patients underwent surgery for LVOT obstruction.
      Multivariable Cox proportional analysis demonstrated % age-gender predicted peak
      VO2 (hazard ratio [HR] 0.96 [0.93-0.98]), normal vs abnormal HRR (HR 0.48 [0.32
      0.73]), higher LVEF (HR 0.96 [0.93-0.98]), surgery (0.53 [0.33-0.83]), and atrial
      fibrillation (HR 1.65 [1.04-2.60]) were associated with outcomes (all P < .05).
      CONCLUSIONS: In HCM patients undergoing CPT, a higher % of achieved age-gender
      predicted VO2 and surgical relief of LVOT obstruction were associated with better
      outcomes, whereas abnormal HRR, atrial fibrillation, and lower LVEF were
      associated with worse outcomes.

PMID- 25965717
TI  - Effect of additive renin inhibition with aliskiren on renal blood flow in
      patients with Chronic Heart Failure and Renal Dysfunction (Additive Renin
      Inhibition with Aliskiren on renal blood flow and Neurohormonal Activation in
      patients with Chronic Heart Failure and Renal Dysfunction).
AB  - AIMS: We examined the effect of the renin inhibitor, aliskiren, on renal blood
      flow (RBF) in patients with heart failure with reduced ejection fraction (HFREF)
      and decreased glomerular filtration rate (GFR). Renal blood flow is the main
      determinant of GFR in HFREF patients. Both reduced GFR and RBF are associated
      with increased mortality. Aliskiren can provide additional renin-angiotensin
      aldosterone system inhibition and increases RBF in healthy individuals. METHODS
      AND RESULTS: Patients with left ventricular ejection fraction <=45% and estimated
      GFR 30 to 75 mL/min per 1.73 m(2) on optimal medical therapy were randomized 2:1
      to receive aliskiren 300 mg once daily or placebo. Renal blood flow and GFR were
      measured using radioactive-labeled (125)I-iothalamate and (131)I-hippuran at
      baseline and 26 weeks. After 41 patients were included, the trial was halted
      based on an interim safety analysis showing futility. Mean age was 68 +/- 9
      years, 82% male, GFR (49 +/- 16 mL/min per 1.73 m(2)), RBF (294 +/- 77 mL/min per
      1.73 m(2)), and NT-proBNP 999 (435-2040) pg/mL. There was a nonsignificant change
      in RBF after 26 weeks in the aliskiren group compared with placebo (-7.1 +/- 30
      vs +14 +/- 54 mL/min per 1.73 m(2); P = .16). However, GFR decreased
      significantly in the aliskiren group compared with placebo (-2.8 +/- 6.0 vs +4.4
      +/- 9.6 mL/min per 1.73 m(2); P = .01) as did filtration fraction (-2.2 +/- 3.3
      vs +1.1 +/- 3.1%; P = .01). There were no significant differences in plasma
      aldosterone, NT-proBNP, urinary tubular markers, or adverse events. Plasma renin
      activity was markedly reduced in the aliskiren group versus placebo throughout
      the treatment phase (P = .007). CONCLUSIONS: Adding aliskiren on top of optimal
      HFREF medical therapy did not improve RBF and was associated with a reduction of
      GFR and filtration fraction.

PMID- 25965718
TI  - The proxy of renal function that most accurately predicts short- and long-term
      outcome after acute coronary syndrome.
AB  - AIMS: The aim of this study is to determine the most accurate renal function
      formula that predicts short- and long-term mortality in a wide spectrum of acute
      coronary syndrome (ACS) patients. METHODS AND RESULTS: We analyzed 8,726
      consecutive patients (46.3% ST-elevation myocardial infarction [STEMI] and 53.7%
      non-ST-elevation ACS [NSTE-ACS]) enrolled in the ACS survey in Israel. Renal
      function, assessed using 5 formulas as proxies of creatinine clearance or
      estimated glomerular filtration rate (Cockcroft-Gault, modification of diet in
      renal disease [MDRD], Chronic Kidney Disease Epidemiology Collaboration, Mayo
      quadratic, and inulin clearance based), varied in applying the different
      formulas. For both STEMI and NSTE-ACS patients, the Mayo formula yielded the
      highest mean value (88.9 +/- 27.7 and 81.4 +/- 29.2 mL/min per 1.73 m(2),
      respectively) and Chronic Kidney Disease Epidemiology Collaboration the lowest
      (73.0 +/- 23.1 and 67.0 +/- 24.1 mL/min per 1.73 m(2), respectively). Using
      multivariate analysis, worse renal function was independently associated with
      increased mortality risk by 30% to 40% for each decrement of 10 U of creatinine
      clearance or estimated glomerular filtration rate in STEMI patients and by 25% to
      30% for NSTE-ACS patients, using all 5 formulas. The only formula that more
      accurately predicted 1-year mortality than the MDRD formula was the Mayo
      quadratic formula with a 1-year net reclassification index of 0.26 and 0.14 for
      STEMI and NSTE-ACS patients, respectively, after multivariable adjustment.
      CONCLUSION: Worse renal function was an independent predictor for short- and long
      term mortality using all 5 formulas in a broad spectrum of ACS patients, but only
      the Mayo quadratic formula had better accuracy in predicting mortality relative
      to the MDRD, suggesting that it may be the preferred prognosticator among ACS
      patients.

PMID- 25965719
TI  - Clinical benefit of spironolactone in patients with acute decompensated heart
      failure and severe renal dysfunction: Data from the Korean Heart Failure
      Registry.
AB  - BACKGROUNDS: We investigated the relationship between spironolactone use and all
      cause mortality in acute decompensated heart failure (ADHF) patients with severe
      renal dysfunction. The clinical benefit of spironolactone in the treatment of
      heart failure (HF) has been described in several large randomized clinical
      trials. However, its clinical benefits have not been studied in hospitalized ADHF
      patients with severe renal dysfunction (estimated glomerular filtration rate
      [eGFR] <45 mL/min per 1.73 m(2)). METHODS AND RESULTS: We retrospectively
      analyzed data from the Korean Heart Failure Registry. We included 1,035 ADHF
      patients with severe renal dysfunction. In Kaplan-Meier survival analysis, all
      cause mortality in the spironolactone-treated group was significantly lower than
      that in the nonspironolactone group (18.1% vs 24.9%, respectively, log rank P =
      .028). However, spironolactone use was not an independent predictor after
      adjusting other HF risk factors (hazard ratio 0.974, 95% CI 0.681-1.392, P =
      .884) and after propensity score matching (P = .115). In subgroup analysis, the
      clinical benefit of spironolactone use was preserved in women, prehospital
      spironolactone use, the chronic kidney disease stage 3b (eGFR 30-44 mL/min per
      1.73 m(2)), and the appropriate spironolactone use (eGFR >=30 mL/min per 1.73
      m(2) and K <=5.0 mmol/L). CONCLUSION: The spironolactone therapy was not
      beneficial in ADHF patients with severe renal dysfunction after multivariable
      adjusting and propensity score matching. However, we reassured the current HF
      guidelines for spironolactone use and the clinical benefit in chronic kidney
      disease stage 3b should be assessed in future clinical trial.

PMID- 25965721
TI  - Cost comparison of transcatheter and operative closures of ostium secundum atrial
      septal defects.
AB  - BACKGROUND: Clinical outcomes for transcatheter and operative closures of atrial
      septal defects (ASDs) are similar. Economic cost for each method has not been
      well described. METHODS: A single-center retrospective cohort study of children
      and adults<30 years of age undergoing closure for single secundum ASD from
      January 1, 2007, to April 1, 2012, was performed to measure differences in
      inflation-adjusted cost of operative and transcatheter closures of ASD. A
      propensity score weight-adjusted multivariate regression model was used in an
      intention-to-treat analysis. Costs for reintervention and crossover admissions
      were included in primary analysis. RESULTS: A total of 244 subjects were included
      in the study (64% transcatheter and 36% operative), of which 2% (n = 5) were >=18
      years. Crossover rate from transcatheter to operative group was 3%. Risk of
      reintervention (P = .66) and 30-day mortality (P = .37) were not significantly
      different. In a multivariate model, adjusted cost of operative closure was 2012
      US $60,992 versus 2012 US $55,841 for transcatheter closure (P < .001).
      Components of total cost favoring transcatheter closure were length of stay,
      medications, and follow-up radiologic and laboratory testing, overcoming higher
      costs of procedure and echocardiography. Professional costs did not differ. The
      rate of 30-day readmission was greater in the operative cohort, further
      increasing the cost advantage of transcatheter closure. Sensitivity analyses
      demonstrated that costs of follow-up visits influenced relative cost but that
      device closure remained favorable over a broad range of crossover and
      reintervention rates. CONCLUSION: For single secundum ASD, cost comparison
      analysis favors transcatheter closure over the short term. The cost of follow-up
      regimens influences the cost advantage of transcatheter closure.

PMID- 25965720
TI  - Race-ethnic differences in subclinical left ventricular systolic dysfunction by
      global longitudinal strain: A community-based cohort study.
AB  - BACKGROUND: Race-ethnic differences exist in the epidemiology of heart failure,
      with blacks experiencing higher incidence and worse prognosis. Left ventricular
      (LV) systolic dysfunction (LVSD) detected by speckle-tracking global longitudinal
      strain (GLS) is a predictor of cardiovascular events including heart failure. It
      is not known whether race-ethnic differences in GLS-LVSD exist in subjects
      without overt LV dysfunction. METHODS: Participants from a triethnic community
      based study underwent 2-dimensional echocardiography with assessment of LV
      ejection fraction (LVEF) and GLS by speckle-tracking. Participants with LVEF <50%
      were excluded. Left ventricular systolic dysfunction by GLS was defined as GLS
      >95% percentile in a healthy sample (-14.7%). RESULTS: Of the 678 study
      participants (mean age 71 +/- 9 years, 61% women), 114 were blacks; 464,
      Hispanics; and 100, whites. Global longitudinal strain was significantly lower in
      blacks (-16.5% +/- 3.5%) than in whites (-17.5% +/- 3.0%) and Hispanics (-17.3%
      +/- 2.9%) in both univariate (P = .015) and multivariate analyses (P = .011),
      whereas LVEF was not significantly different between the 3 groups (64.3% +/-
      4.6%, 63.4% +/- 4.9%, 64.7% +/- 4.9%, respectively, univariate P = .064,
      multivariate P = .291). Left ventricular systolic dysfunction by GLS was more
      frequent in blacks (27.2%) than in whites (19.0%) and Hispanics (14.9%, P =
      .008). In multivariate analysis adjusted for confounders and cardiovascular risk
      factors, blacks were significantly more likely to have GLS-LVSD (adjusted odds
      ratio 2.6, 95% CIs 1.4-4.7, P = .002) compared to the other groups. CONCLUSIONS:
      Among participants from a triethnic community cohort, black race was associated
      with greater degree of subclinical LVSD by GLS than other race-ethnic groups.
      This difference was independent of confounders and cardiovascular risk factors.

PMID- 25965722
TI  - The effect of an apolipoprotein A-I-containing high-density lipoprotein-mimetic
      particle (CER-001) on carotid artery wall thickness in patients with homozygous
      familial hypercholesterolemia: The Modifying Orphan Disease Evaluation (MODE)
      study.
AB  - BACKGROUND: Patients with homozygous familial hypercholesterolemia (HoFH) are at
      extremely elevated risk for early cardiovascular disease because of exposure to
      elevated low-density lipoprotein cholesterol (LDL-C) plasma levels from birth.
      Lowering LDL-C by statin therapy is the cornerstone for cardiovascular disease
      prevention, but the residual risk in HoFH remains high, emphasizing the need for
      additional therapies. In the present study, we evaluated the effect of serial
      infusions with CER-001, a recombinant human apolipoprotein A-I (apoA-I)
      containing high-density lipoprotein-mimetic particle, on carotid artery wall
      dimensions in patients with HoFH. METHODS AND RESULTS: Twenty-three patients
      (mean age 39.4 +/- 13.5 years, mean LDL-C 214.2 +/- 81.5 mg/dL) with genetically
      confirmed homozygosity or compound heterozygosity for LDLR, APOB, PCSK9, or
      LDLRAP1 mutations received 12 biweekly infusions with CER-001 (8 mg/kg). Before
      and 1 hour after the first infusion, lipid values were measured. Magnetic
      resonance imaging (3-T magnetic resonance imaging) scans of the carotid arteries
      were acquired at baseline and after 24 weeks to assess changes in artery wall
      dimensions. After CER-001 infusion, apoA-I increased from 114.8 +/- 20.7 mg/dL to
      129.3 +/- 23.0 mg/dL. After 24 weeks, mean vessel wall area (primary end point)
      decreased from 17.23 to 16.75 mm(2) (P = .008). A trend toward reduction of mean
      vessel wall thickness was observed (0.75 mm at baseline and 0.74 mm at follow-up,
      P = .0835). CONCLUSIONS: In HoFH, 12 biweekly infusions with an apoA-I-containing
      high-density lipoprotein-mimetic particle resulted in a significant reduction in
      carotid mean vessel wall area, implying that CER-001 may reverse atherogenic
      changes in the arterial wall on top of maximal low-density lipoprotein-lowering
      therapy. This finding supports further clinical evaluation of apoA-I-containing
      particles in patients with HoFH.

PMID- 25965723
TI  - Response to letter to the editor by Stephen W. Smith, MD.

PMID- 25965724
TI  - Transesophageal echocardiography is an indispensable guide during thrombolytic
      therapy for prosthetic valve thrombosis.

PMID- 25965725
TI  - Regarding manuscript: "Incidence, angiographic features, and outcomes of patients
      presenting with subtle ST-elevation myocardial infarction".

PMID- 25965726
TI  - Hierarchical nanostructures self-assembled from a mixture system containing rod
      coil block copolymers and rigid homopolymers.
AB  - Self-assembly behavior of a mixture system containing rod-coil block copolymers
      and rigid homopolymers was investigated by using Brownian dynamics simulations.
      The morphologies of formed hierarchical self-assemblies were found to be
      dependent on the Lennard-Jones (LJ) interaction epsilonRR between rod blocks,
      lengths of rod and coil blocks in copolymer, and mixture ratio of block
      copolymers to homopolymers. As the epsilonRR value decreases, the self-assembled
      structures of mixtures are transformed from an abacus-like structure to a helical
      structure, to a plain fiber, and finally are broken into unimers. The order
      parameter of rod blocks was calculated to confirm the structure transition.
      Through varying the length of rod and coil blocks, the regions of thermodynamic
      stability of abacus, helix, plain fiber, and unimers were mapped. Moreover, it
      was discovered that two levels of rod block ordering exist in the helices. The
      block copolymers are helically wrapped on the homopolymer bundles to form helical
      string, while the rod blocks are twistingly packed inside the string. In
      addition, the simulation results are in good agreement with experimental
      observations. The present work reveals the mechanism behind the formation of
      helical (experimentally super-helical) structures and may provide useful
      information for design and preparation of the complex structures. 

PMID- 25965727
TI  - Near-infrared-absorbing gold nanopopcorns with iron oxide cluster core for
      magnetically amplified photothermal and photodynamic cancer therapy.
AB  - We present the synthesis and application of a new type of dual magnetic and
      plasmonic nanostructures for magnetic-field-guided drug delivery and combined
      photothermal and photodynamic cancer therapy. Near-infrared-absorbing gold
      nanopopcorns containing a self-assembled iron oxide cluster core were prepared
      via a seed-mediated growth method. The hybrid nanostructures are
      superparamagnetic and show great photothermal conversion efficiency (eta=61%)
      under near-infrared irradiation. Compact and stable nanocomplexes for
      photothermal-photodynamic therapy were formed by coating the nanoparticles with
      near-infrared-absorbing photosensitizer silicon 2,3-naphthalocyannie dihydroxide
      and stabilization with poly(ethylene glycol) linked with 11-mercaptoundecanoic
      acid. The nanocomplex showed enhanced release and cellular uptake of the
      photosensitizer with the use of a gradient magnetic field. In vitro studies using
      two different cell lines showed that the dual mode photothermal and photodynamic
      therapy with the assistance of magnetic-field-guided drug delivery dramatically
      improved the therapeutic efficacy of cancer cells as compared to the combination
      treatment without using a magnetic field and the two treatments alone. The "three
      in-one" nanocomplex has the potential to carry therapeutic agents deep into a
      tumor through magnetic manipulation and to completely eradicate tumors by
      subsequent photothermal and photodynamic therapies without systemic toxicity.

PMID- 25965728
TI  - Next-generation genome editing.

PMID- 25965729
TI  - CRISPR germline editing reverberates through biotech industry.

PMID- 25965730
TI  - Startups use short-read data to expand long-read sequencing market.

PMID- 25965731
TI  - Court sides with Sandoz over Neupogen biosimilar.

PMID- 25965732
TI  - FDA approves 23andMe gene carrier test.

PMID- 25965733
TI  - Human cell assays for new medicines now open access.

PMID- 25965734
TI  - Epigenome drug approved after setback.

PMID- 25965735
TI  - Keytruda UK's first early-access drug.

PMID- 25965710
TI  - Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in
      Acute Coronary Syndrome, a long-term cardiovascular end point trial of
      lixisenatide versus placebo.
AB  - BACKGROUND: Cardiovascular (CV) disease is the leading cause of morbidity and
      mortality in patients with type 2 diabetes mellitus (T2DM). Furthermore, patients
      with T2DM and acute coronary syndrome (ACS) have a particularly high risk of CV
      events. The glucagon-like peptide 1 receptor agonist, lixisenatide, improves
      glycemia, but its effects on CV events have not been thoroughly evaluated.
      METHODS: ELIXA (www.clinicaltrials.gov no. NCT01147250) is a randomized, double
      blind, placebo-controlled, parallel-group, multicenter study of lixisenatide in
      patients with T2DM and a recent ACS event. The primary aim is to evaluate the
      effects of lixisenatide on CV morbidity and mortality in a population at high CV
      risk. The primary efficacy end point is a composite of time to CV death, nonfatal
      myocardial infarction, nonfatal stroke, or hospitalization for unstable angina.
      Data are systematically collected for safety outcomes, including hypoglycemia,
      pancreatitis, and malignancy. RESULTS: Enrollment began in July 2010 and ended in
      August 2013; 6,068 patients from 49 countries were randomized. Of these, 69% are
      men and 75% are white; at baseline, the mean +/- SD age was 60.3 +/- 9.7 years,
      body mass index was 30.2 +/- 5.7 kg/m(2), and duration of T2DM was 9.3 +/- 8.2
      years. The qualifying ACS was a myocardial infarction in 83% and unstable angina
      in 17%. The study will continue until the positive adjudication of the protocol
      specified number of primary CV events. CONCLUSION: ELIXA will be the first trial
      to report the safety and efficacy of a glucagon-like peptide 1 receptor agonist
      in people with T2DM and high CV event risk.

PMID- 25965736
TI  - Biogen's early Alzheimer's data raise hopes, some eyebrows.

PMID- 25965737
TI  - Corrections.

PMID- 25965738
TI  - First-in-class HIV drug enters phase 3 trials.

PMID- 25965744
TI  - Startups on the menu: Atreca.

PMID- 25965740
TI  - Lilly pays $50 million for Korean BTK.

PMID- 25965745
TI  - Precision medicine and the FDA's draft guidance on laboratory-developed tests.

PMID- 25965746
TI  - What's behind a 'genetically engineered' label?

PMID- 25965747
TI  - Nature biotechnology responds to Melchett correspondence.

PMID- 25965748
TI  - Transparency in GM food labeling.

PMID- 25965749
TI  - Oversight of human inheritable genome modification.

PMID- 25965750
TI  - Defining digital medicine.

PMID- 25965751
TI  - The digital phenotype.

PMID- 25965752
TI  - What Ebola tells us about outbreak diagnostic readiness.

PMID- 25965753
TI  - Biotech's wellspring--a survey of the health of the private sector in 2014.

PMID- 25965755
TI  - A solution to the controversy on plant variety protection in Africa.

PMID- 25965754
TI  - CRISPR germline engineering--the community speaks.

PMID- 25965757
TI  - Putting cells in their place.

PMID- 25965758
TI  - Unraveling the fabric of polyploidy.

PMID- 25965759
TI  - Islet implantation in a pocket.

PMID- 25965761
TI  - Corrigendum: Taking charge of siRNA delivery.

PMID- 25965762
TI  - Erratum: Selling long life.

PMID- 25965763
TI  - Erratum: Modeling the course of amyotrophic lateral sclerosis.

PMID- 25965766
TI  - Conserved Epigenetic Mechanisms Could Play a Key Role in Regulation of
      Photosynthesis and Development-Related Genes during Needle Development of Pinus
      radiata.
AB  - Needle maturation is a complex process that involves cell growth, differentiation
      and tissue remodelling towards the acquisition of full physiological competence.
      Leaf induction mechanisms are well known; however, those underlying the
      acquisition of physiological competence are still poorly understood, especially
      in conifers. We studied the specific epigenetic regulation of genes defining
      organ function (PrRBCS and PrRBCA) and competence and stress response (PrCSDP2
      and PrSHMT4) during three stages of needle development and one de-differentiated
      control. Gene-specific changes in DNA methylation and histone were analysed by
      bisulfite sequencing and chromatin immunoprecipitation (ChIP). The expression of
      PrRBCA and PrRBCS increased during needle maturation and was associated with the
      progressive loss of H3K9me3, H3K27me3 and the increase in AcH4. The maturation
      related silencing of PrSHMT4 was correlated with increased H3K9me3 levels, and
      the repression of PrCSDP2, to the interplay between AcH4, H3K27me3, H3K9me3 and
      specific DNA methylation. The employ of HAT and HDAC inhibitors led to a further
      determination of the role of histone acetylation in the regulation of our target
      genes. The integration of these results with high-throughput analyses in
      Arabidopsis thaliana and Populus trichocarpa suggests that the specific
      epigenetic mechanisms that regulate photosynthetic genes are conserved between
      the analysed species. 

PMID- 25965768
TI  - Couple Treatment for Alcohol Use Disorder and Posttraumatic Stress Disorder:
      Pilot Results From U.S. Military Veterans and Their Partners.
AB  - We studied 13 U.S. male military veterans and their female partners who consented
      to participate in an uncontrolled trial of couple treatment for alcohol use
      disorder and posttraumatic stress disorder (CTAP). CTAP is a 15-session,
      manualized therapy, integrating behavioral couples therapy for alcohol use
      disorder (AUD) with cognitive-behavioral conjoint therapy for posttraumatic
      stress disorder (PTSD). Due to ineligibility (n = 1) and attrition (n = 3), 9
      couples completed the study, and 7 completed 12 or more sessions. There were 8
      veterans who showed clinically reliable pre- to posttreatment reduction of PTSD
      outcomes. There were also significant group-level reductions in clinician-,
      veteran-, and partner-rated PTSD symptoms (d = 0.94 to 1.71). Most veterans
      showed clinically reliable reductions in percentage days of heavy drinking. Group
      level reduction in veterans' percentage days of heavy drinking was significant (d
      = 1.01). There were 4 veterans and 3 partners with clinically reliable reductions
      in depression, and group-level change was significant for veterans (d = 0.93) and
      partners (d = 1.06). On relationship satisfaction, 3 veterans and 4 partners had
      reliable improvements, and 2 veterans and 1 partner had reliable deterioration.
      Group-level findings were nonsignificant for veteran relationship satisfaction (d
      = 0.26) and for partners (d = 0.52). These findings indicate that CTAP may be a
      promising intervention for individuals with comorbid PTSD and AUD who have
      relationship partners. 

PMID- 25965769
TI  - Periodic solution for state-dependent impulsive shunting inhibitory CNNs with
      time-varying delays.
AB  - In this paper, we consider existence and global exponential stability of periodic
      solution for state-dependent impulsive shunting inhibitory cellular neural
      networks with time-varying delays. By means of B-equivalence method, we reduce
      these state-dependent impulsive neural networks system to an equivalent fix time
      impulsive neural networks system. Further, by using Mawhin's continuation theorem
      of coincide degree theory and employing a suitable Lyapunov function some new
      sufficient conditions for existence and global exponential stability of periodic
      solution are obtained. Previous results are improved and extended. Finally, we
      give an illustrative example with numerical simulations to demonstrate the
      effectiveness of our theoretical results. 

PMID- 25965770
TI  - Discontinuous Lyapunov approach to state estimation and filtering of jumped
      systems with sampled-data.
AB  - This paper is concerned with the sampled-data state estimation and H(infinity)
      filtering for a class of Markovian jump systems with the discontinuous Lyapunov
      approach. The system measurements are sampled and then transmitted to the
      estimator and filter in order to estimate the state of the jumped system under
      consideration. The corresponding error dynamics is represented by a system with
      two types of delays: one is from the system itself, and the other from the
      sampling period. As the delay due to sampling is discontinuous, a corresponding
      discontinuous Lyapunov functional is constructed, and sufficient conditions are
      established so as to guarantee both the asymptotic mean-square stability and the
      H(infinity) performance for the filtering error systems. The explicit expressions
      of the desired estimator and filter are further provided. Finally, two simulation
      examples are given to illustrate the design procedures and performances of the
      proposed method.

PMID- 25965771
TI  - Computer aided diagnosis of schizophrenia on resting state fMRI data by ensembles
      of ELM.
AB  - Resting state functional Magnetic Resonance Imaging (rs-fMRI) is increasingly
      used for the identification of image biomarkers of brain diseases or psychiatric
      conditions such as schizophrenia. This paper deals with the application of
      ensembles of Extreme Learning Machines (ELM) to build Computer Aided Diagnosis
      systems on the basis of features extracted from the activity measures computed
      over rs-fMRI data. The power of ELM to provide quick but near optimal solutions
      to the training of Single Layer Feedforward Networks (SLFN) allows extensive
      exploration of discriminative power of feature spaces in affordable time with off
      the-shelf computational resources. Exploration is performed in this paper by an
      evolutionary search approach that has found functional activity map features
      allowing to achieve quite successful classification experiments, providing
      biologically plausible voxel-site localizations. 

PMID- 25965772
TI  - Molecular Dynamics Simulations of CO2/Water/Quartz Interfacial Properties: Impact
      of CO2 Dissolution in Water.
AB  - The safe trapping of carbon dioxide (CO2) in deep saline aquifers is one of the
      major concerns of CO2 sequestration. The amount of capillary trapping is
      dominated by the capillary pressure of water and CO2 inside the reservoir, which
      in turn is controlled by the interfacial tension (IFT) and the contact angle (CA)
      of CO2/water/rock systems. The measurement of IFT and CA could be very
      challenging at reservoir conditions, especially in the presence of toxic
      cocontaminants. Thus, the ability to accurately predict these interfacial
      properties at reservoir conditions is very advantageous. Although the majority of
      existing molecular dynamics (MD) studies of CO2/water/mineral systems were able
      to capture the trends in IFT and CA variations with pressure and temperature,
      their predictions often deviated from experimental data, possibly due to
      erroneous models and/or overlooked chemical reactions. The objective of this
      study was to improve the MD predictions of IFT and CA of CO2/water/quartz systems
      at various pressure and temperature conditions by (i) considering the chemical
      reactions between CO2 and water and (ii) using a new molecular model for alpha
      quartz surface. The results showed that the presence of carbonic acid at the
      CO2/water interface improved the predictions of IFT, especially at low
      temperature and high pressure where more CO2 dissolution occurs. On the other
      hand, the effect on CA was minor. The slight decrease in CA observed across the
      pressure range investigated could be attributed to an increase in the total
      number of H-bonds between fluid molecules and quartz surface. 

PMID- 25965773
TI  - Effect of Elastic Strain Fluctuation on Atomic Layer Growth of Epitaxial Silicide
      in Si Nanowires by Point Contact Reactions.
AB  - Effects of strain impact a range of applications involving mobility change in
      field-effect-transistors. We report the effect of strain fluctuation on epitaxial
      growth of NiSi2 in a Si nanowire via point contact and atomic layer reactions,
      and we discuss the thermodynamic, kinetic, and mechanical implications. The
      generation and relaxation of strain shown by in situ TEM is periodic and in
      synchronization with the atomic layer reaction. The Si lattice at the epitaxial
      interface is under tensile strain, which enables a high solubility of
      supersaturated interstitial Ni atoms for homogeneous nucleation of an epitaxial
      atomic layer of the disilicide phase. The tensile strain is reduced locally
      during the incubation period of nucleation by the dissolution of supersaturated
      Ni atoms in the Si lattice but the strained-Si state returns once the atomic
      layer epitaxial growth of NiSi2 occurs by consuming the supersaturated Ni. 

PMID- 25965775
TI  - Chronic cutaneous lichenoid graft-versus-host disease at the area of herpes
      zoster infection and at a vaccination site.
AB  - Cutaneous graft-versus-host disease (GVHD) is a frequent complication of
      allogeneic bone marrow transplant and haematopoietic cell transplantation, but it
      is rarely presented as a Wolf's isotopic response. We report a patient who
      developed chronic lichenoid GVHD following the dermatomes previously affected by
      varicella zoster virus (VZV) infection. Nineteen months later, the same patient
      suffered from reactivation of GVHD at the injection site of an influenza
      vaccination. We review the literature concerning GVHD appearing after VZV
      infection and discuss the possible implications of this case and the pathogenic
      hypotheses. 

PMID- 25965774
TI  - H2S induced coma and cardiogenic shock in the rat: Effects of phenothiazinium
      chromophores.
AB  - CONTEXT: Hydrogen sulfide (H2S) intoxication produces an acute depression in
      cardiac contractility-induced circulatory failure, which has been shown to be one
      of the major contributors to the lethality of H2S intoxication or to the
      neurological sequelae in surviving animals. Methylene blue (MB), a
      phenothiazinium dye, can antagonize the effects of the inhibition of
      mitochondrial electron transport chain, a major effect of H2S toxicity.
      OBJECTIVES: We investigated whether MB could affect the immediate outcome of H2S
      induced coma in un-anesthetized animals. Second, we sought to characterize the
      acute cardiovascular effects of MB and two of its demethylated metabolites-azure
      B and thionine-in anesthetized rats during lethal infusion of H2S. MATERIALS AND
      METHODS: First, MB (4 mg/kg, intravenous [IV]) was administered in non-sedated
      rats during the phase of agonal breathing, following NaHS (20 mg/kg, IP)-induced
      coma. Second, in 4 groups of urethane-anesthetized rats, NaHS was infused at a
      rate lethal within 10 min (0.8 mg/min, IV). Whenever cardiac output (CO) reached
      40% of its baseline volume, MB, azure B, thionine, or saline were injected, while
      sulfide infusion was maintained until cardiac arrest occurred. RESULTS: Seventy
      five percent of the comatose rats that received saline (n = 8) died within 7 min,
      while all the 7 rats that were given MB survived (p = 0.007). In the anesthetized
      rats, arterial, left ventricular pressures and CO decreased during NaHS infusion,
      leading to a pulseless electrical activity within 530 s. MB produced a
      significant increase in CO and dP/dtmax for about 2 min. A similar effect was
      produced when MB was also injected in the pre-mortem phase of sulfide exposure,
      significantly increasing survival time. Azure B produced an even larger increase
      in blood pressure than MB, while thionine had no effect. CONCLUSION: MB can
      counteract NaHS-induced acute cardiogenic shock; this effect is also produced by
      azure B, but not by thionine, suggesting that the presence of methyl groups is a
      prerequisite for producing this protective effect.

PMID- 25965776
TI  - 1,3,4-Oxadiazoles: An emerging scaffold to target growth factors, enzymes and
      kinases as anticancer agents.
AB  - Five member heterocyclic 1,3,4-oxadiazole nucleus find unique place in medicinal
      chemistry and plays significant role in producing anticancer activity. The small
      and simple 1,3,4-oxadiazole nucleus is present in various compounds involved in
      research aimed at evaluating new products that posses interesting pharmacological
      properties such as antitumour activity. Mono and 2,5-di-substituted-1,3,4
      oxadiazole derivatives have attracted considerable attention owing to their
      effective biological activity and extensive use. The important mechanism involved
      during its tumour suppression is related with the inhibition of different growth
      factors, enzymes and kinases including telomerase enzyme, histone deacetylase
      (HDAC), methionine aminopeptidase (MetAP), thymidylate synthase (TS), glycogen
      synthase kinase-3 (GSK), epidermal growth factor (EGF), vascular endothelial
      growth factor (VEGF) and focal adhesion kinase (FAK). The focused criteria of
      this review is to highlights the targeted inhibitory activity of 1,3,4-oxadiazole
      derivatives and their structure activity relationship to generate potential
      anticancer agents. 

PMID- 25965777
TI  - Structure-activity relationships and molecular studies of novel
      arylpiperazinylalkyl purine-2,4-diones and purine-2,4,8-triones with
      antidepressant and anxiolytic-like activity.
AB  - A novel series of arylpiperazinylalkyl purine-2,4-diones (4-27) and purine-2,4,8
      triones (31-38) was synthesized and tested to evaluated their affinity for the
      serotoninergic (5-HT1A, 5-HT6, 5-HT7) and dopaminergic (D2) receptors. Compounds
      with purine-2,4-dione nucleus generally had affinity values higher than the
      corresponding purine-2,4,8-trione compounds. A spectrum of receptor activities
      was observed for compounds with a substituent at the 7-position of the
      imidazo[2,1-f]purine-2,4-dione system and some potent 5-HT1A (18, 25), 5-HT7 (14)
      and mixed 5-HT1A/5-HT7 (8, 9) receptor ligands with additional affinity for
      dopamine D2 receptors (15) has been identified. Moreover, docking studies proved
      that a substituent at the 7-position of 1,3-dimethyl-(1H,8H)-imidazo[2,1-f]purine
      2,4-dione could be essential for receptor affinity and selectivity, especially
      towards 5-HT1A and 5-HT7. The results of the preliminary pharmacological in vivo
      studies of selected derivatives of 1,3-dimethyl-(1H,8H)-imidazo[2,1-f]purine-2,4
      dione, including 9 as a potential anxiolytic, 8 and 15 as potential
      antidepressants, and 18 and 25 as potential antidepressant and anxiolytic agents.

PMID- 25965778
TI  - Novel myricetin derivatives: Design, synthesis and anticancer activity.
AB  - Telomere and telomerase were closely related to occurrence and development of
      some cancers. To enhance ability of myricetin moiety for inhibiting telomerase,
      we designed a series of novel myricetin derivatives based on reasonable analysis.
      The telomerase inhibition assay showed that compound 6d displayed the most potent
      inhibitory activity with IC50 value of 0.91 MUM. The anticancer activity assay
      showed that 6d exhibited high activity against human breast cells MDA-MB-231. The
      docking simulation of compound 6d was performed to get the probable binding
      model, the results demonstrated that the furan ring inserted into the active site
      deeply and had hydrophobic interactions with residues of Phe 568, Pro 627, four
      methoxy groups had hydrophobic interactions with residues of Phe 568, Pro 627,
      Lys 902, Val 904 and Pro 929. Western blot results showed that expression of p65
      and TERT protein was clearly down-regulated by compound 6d. These data support
      further studies for the rational design of more efficient p65 and TERT
      modulators. 

PMID- 25965779
TI  - New efficient artemisinin derived agents against human leukemia cells, human
      cytomegalovirus and Plasmodium falciparum: 2nd generation 1,2,4-trioxane
      ferrocene hybrids.
AB  - In our ongoing search for highly active hybrid molecules exceeding their parent
      compounds in anticancer, antimalaria as well as antiviral activity and being an
      alternative to the standard drugs, we present the synthesis and biological
      investigations of 2nd generation 1,2,4-trioxane-ferrocene hybrids. In vitro tests
      against the CCRF-CEM leukemia cell line revealed di-1,2,4-trioxane-ferrocene
      hybrid 7 as the most active compound (IC50 of 0.01 MUM). Regarding the activity
      against the multidrug resistant subline CEM/ADR5000, 1,2,4-trioxane-ferrocene
      hybrid 5 showed a remarkable activity (IC50 of 0.53 MUM). Contrary to the
      antimalaria activity of hybrids 4-8 against Plasmodium falciparum 3D7 strain with
      slightly higher IC50 values (between 7.2 and 30.2 nM) than that of their parent
      compound DHA, hybrids 5-7 possessed very promising activity (IC50 values lower
      than 0.5 MUM) against human cytomegalovirus (HCMV). The application of 1,2,4
      trioxane-ferrocene hybrids against HCMV is unprecedented and demonstrated here
      for the first time. 

PMID- 25965780
TI  - Rhodium(II)-catalysed intramolecular C-H insertion alpha- to oxygen: reactivity,
      selectivity and applications to natural product synthesis.
AB  - The selective functionalisation of C-H bonds is a powerful strategy for the
      construction of organic molecules and the Rh(II)-catalysed C-H insertion reaction
      is a particularly robust and useful tool for this purpose. This review discusses
      the insertion of Rh(II) carbenes into C-H bonds that are activated by alpha
      oxygen substituents, focusing on the trends that have been observed in reactivity
      and selectivity, and the applications of this reaction to the total synthesis of
      complex natural products.

PMID- 25965783
TI  - Mechanically Induced Multicolor Change of Luminescent Materials.
AB  - Mechanofluorochromic or piezochromic fluorescence chemistry involves the
      switching and tuning of the luminescent properties of solid-state materials
      induced by exogenous forces, such as grinding, shearing, compression, tension,
      and so forth. Up until now, most reported mechanochromic systems, including
      liquid crystals, organic molecules, organometallic compounds, polymers, and dye
      doped polymers, have displayed reversible two-color changes, which arise from
      either supramolecular or chemical structure transformations. However, fluorescent
      materials that undergo mechanically induced multicolor changes remain rare; this
      Minireview is focused on such materials. Topics are categorized according to the
      different applied forces that are required to induce the multicolor change,
      including mechanical control of either the supramolecular structures or the
      chemical structures, and mechanical control of both the supramolecular structures
      and chemical structures. 

PMID- 25965781
TI  - An ex vivo model for studying hepatic schistosomiasis and the effect of released
      protein from dying eggs.
AB  - BACKGROUND: We report the use of an ex vivo precision cut liver slice (PCLS)
      mouse model for studying hepatic schistosomiasis. In this system, liver tissue is
      unfixed, unfrozen, and alive for maintenance in culture and subsequent molecular
      analysis. METHODS AND FINDINGS: Using thick naive mouse liver tissue and sterile
      culture conditions, the addition of soluble egg antigen (SEA) derived from
      Schistosoma japonicum eggs, followed 4, 24 and 48 hrs time points. Tissue was
      collected for transcriptional analysis and supernatants collected to quantitate
      liver enzymes, cytokines and chemokines. No significant hepatotoxicity was
      demonstrated by supernatant liver enzymes due to the presence of SEA. A
      proinflammatory response was observed both at the transcriptional level and at
      the protein level by cytokine and chemokine bead assay. Key genes observed
      elevated transcription in response to the addition of SEA included: IL1-alpha and
      IL1-beta, IL6, all associated with inflammation. The recruitment of antigen
      presenting cells was reflected in increases in transcription of CD40, CCL4 and
      CSF1. Indications of tissue remodeling were seen in elevated gene expression of
      various Matrix MetalloProteinases (MMP3, 9, 10, 13) and delayed increases in
      TIMP1. Collagen deposition was significantly reduced in the presence of SEA as
      shown in COL1A1 expression by qPCR after 24 hrs culture. Cytokine and chemokine
      analysis of the culture supernatants confirmed the elevation of proteins
      including IL6, CCL3, CCL4 and CXCL5. CONCLUSIONS: This ex vivo model system for
      the synchronised delivery of parasite antigen to liver tissue provides an insight
      into the early phase of hepatic schistosomiasis, corresponding with the release
      of soluble proteins from dying schistosome eggs.

PMID- 25965782
TI  - The effect of oncologists' exercise recommendations on the level of exercise and
      quality of life in survivors of breast and colorectal cancer: A randomized
      controlled trial.
AB  - BACKGROUND: The purpose of the current study was to examine the effect of an
      oncologist's exercise recommendation with and without an exercise motivation
      package on the amount of exercise participation and quality of life (QOL) in
      survivors of breast and colorectal cancer. METHODS: A total of 162 survivors of
      early-stage breast and colorectal cancer who completed primary and adjuvant
      treatments were recruited for the current study. Participants were randomly
      assigned into 1 of 3 groups: 1) control (59 patients); 2) those receiving an
      oncologist's exercise recommendation (53 patients); and 3) those receiving an
      oncologist's exercise recommendation with an exercise motivation package (50
      patients). At baseline and after 4 weeks, the level of exercise participation and
      QOL were assessed. RESULTS: Of the 162 participants, 130 (80.2%) completed the
      trial. Intention-to-treat analysis indicated that participants who received an
      oncologist's exercise recommendation with an exercise motivation package
      significantly increased their level of exercise participation in terms of minutes
      (47.57 added minutes per week; 95% confidence interval, 9.62-85.52 minutes [P
      =.022] vs control) and in Metabolic Equivalent of Task (MET)-hours per week (4.14
      additional MET-hours per week; 95% confidence interval, 1.70-6.58 MET-hours [P
      =.004] vs control) compared with the control group. Participants who received
      only their oncologist's exercise recommendation did not increase their exercise
      participation level. Further analysis demonstrated that role functioning was
      significantly improved among participants who received an oncologist's exercise
      recommendation with an exercise motivation package. CONCLUSIONS: Providing an
      exercise motivation package in addition to the oncologist's exercise
      recommendation to increase the level of exercise among survivors of breast and
      colorectal cancer should be considered.

PMID- 25965784
TI  - Easy Extraction Method To Evaluate delta13C Vanillin by Liquid Chromatography
      Isotopic Ratio Mass Spectrometry in Chocolate Bars and Chocolate Snack Foods.
AB  - An easy extraction method that permits the use of a liquid chromatography
      isotopic ratio mass spectrometry (LC-IRMS) system to evaluate delta(13)C of
      vanillin in chocolate products and industrial flavorings is presented. The method
      applies the determination of stable isotopes of carbon to discriminate between
      natural vanillin from vanilla beans and vanillin from other sources (mixtures
      from beans, synthesis, or biotechnology). A series of 13 chocolate bars and
      chocolate snack foods available on the Italian market and 8 vanilla flavorings
      derived from industrial quality control processes were analyzed. Only 30% of
      products considered in this work that declared "vanilla" on the label showed data
      that permitted the declaration "vanilla" according to European Union (EU)
      Regulation 1334/2008. All samples not citing "vanilla" or "natural flavoring" on
      the label gave the correct declaration. The extraction method is presented with
      data useful for statistical evaluation. 

PMID- 25965786
TI  - Experimental and theoretical study of the decomposition of copper nitrate cluster
      anions.
AB  - Copper nitrate anion clusters Cu(NO3)3(-) and Cu(NO3)2(-) were generated by
      electrospray ionization and studied with collision-induced dissociation and
      energy-resolved mass spectrometry. Collision-induced dissociation resulted in
      three different fragmentation reactions-loss of NO3(-), NO3(*), and NO2(*). The
      type of fragmentation reaction depends on the oxidation state of the metal. The
      Cu(NO3)3(-) cluster showed loss of NO3(*) but no loss of NO2(*), whereas the
      Cu(NO3)2(-) cluster showed loss of NO2(*) but no loss of NO3(*). The
      fragmentation reactions were studied by theoretical methods. These studies show
      loss of NO3(*) corresponds to reduction of the metal charge by electron transfer,
      whereas loss of NO2(*) and metal-oxide bond formation by O(-) abstraction in
      Cu(NO3)2(-) does not necessarily result in the expected oxidation of the metal. 

PMID- 25965789
TI  - Casimir entropy for magnetodielectrics.
AB  - We find the analytic expressions for the Casimir free energy, entropy and
      pressure at low temperature in the configuration of two parallel plates made of
      magnetodielectic material. The cases of constant and frequency-dependent
      dielectic permittivity and magnetic permeability of the plates are considered.
      Special attention is paid to the account of dc conductivity. It is shown that in
      the case of finite static dielectric permittivity and magnetic permeability the
      Nernst heat theorem for the Casimir entropy is satisfied. If the dc conductivity
      is taken into account, the Casimir entropy goes to a positive nonzero limit
      depending on the parameters of a system when the temperature vanishes, i.e. the
      Nernst theorem is violated. The experimental situation is also discussed. 

PMID- 25965788
TI  - High-resolution MALDI-FT-ICR MS imaging for the analysis of metabolites from
      formalin-fixed, paraffin-embedded clinical tissue samples.
AB  - We present the first analytical approach to demonstrate the in situ imaging of
      metabolites from formalin-fixed, paraffin-embedded (FFPE) human tissue samples.
      Using high-resolution matrix-assisted laser desorption/ionization Fourier
      transform ion cyclotron resonance mass spectrometry imaging (MALDI-FT-ICR MSI),
      we conducted a proof-of-principle experiment comparing metabolite measurements
      from FFPE and fresh frozen tissue sections, and found an overlap of 72% amongst
      1700 m/z species. In particular, we observed conservation of biomedically
      relevant information at the metabolite level in FFPE tissues. In biomedical
      applications, we analysed tissues from 350 different cancer patients and were
      able to discriminate between normal and tumour tissues, and different tumours
      from the same organ, and found an independent prognostic factor for patient
      survival. This study demonstrates the ability to measure metabolites in FFPE
      tissues using MALDI-FT-ICR MSI, which can then be assigned to histology and
      clinical parameters. Our approach is a major technical, histochemical, and
      clinicopathological advance that highlights the potential for investigating
      diseases in archived FFPE tissues.

PMID- 25965790
TI  - Expanded Porphyrin-Anion Supramolecular Assemblies: Environmentally Responsive
      Sensors for Organic Solvents and Anions.
AB  - Porphyrins have been used frequently to construct supramolecular assemblies. In
      contrast, noncovalent ensembles derived from expanded porphyrins, larger
      congeners of naturally occurring tetrapyrrole macrocycles, are all but unknown.
      Here we report a series of expanded porphyrin-anion supramolecular assemblies.
      These systems display unique environmentally responsive behavior. Addition of
      polar organic solvents or common anions to the ensembles leads to either a
      visible color change, a change in the fluorescence emission features, or
      differences in solubility. The actual response, which could be followed easily by
      the naked eye, was found to depend on the specifics of the assembly, as well as
      the choice of analyte. Using the ensembles of this study, it proved possible to
      differentiate between common solvents, such as diethyl ether, THF, ethyl acetate,
      acetone, alcohol, acetonitrile, DMF, and DMSO, identify complex solvent systems,
      as well as distinguish between the fluoride, chloride, bromide, nitrate, and
      sulfate anions. 

PMID- 25965791
TI  - The importance of glutamine 294 that affects the ribonuclease H activity of the
      reverse transcriptase of HIV-2 to viral replication.
AB  - Most currently-used antiretroviral drugs inhibit the reverse-transcriptase (RT)
      of HIV. The differences between HIV-1 and HIV-2 RTs explain why some of the anti
      HIV-1 drugs are not effective against HIV-2. One major difference between the two
      HIV RTs is the low ribonuclease H (RNase H) activity of HIV-2 RT relative to HIV
      1 RT. Our previous studies showed that residue Gln294 in HIV-2 RT accounts for
      this RNase H reduction (the comparable residue in HIV-1 RT is Pro294), as the
      Q294P mutant of HIV-2 RT has ~10-fold higher RNase H. Here, we show that
      infectious HIV-2 cannot bear the replacement of the RT's Gln294 by the HIV-1 RT
      Pro counterpart, as it results in substantially reduced HIV-2 replication and
      fast reversions to the wild-type Gln294 virus. These findings prove the critical
      role of maintaining low RT-associated RNase H activity in HIV-2. In contrast, HIV
      1 can tolerate an about 10-fold higher RNase H.

PMID- 25965792
TI  - Interaction of cellular proteins with BCL-xL targeted to cytoplasmic inclusion
      bodies in adenovirus infected cells.
AB  - Adenovirus-mediated apoptosis was suppressed when cellular anti-apoptosis
      proteins (BCL-2 and BCL-xL) were substituted for the viral E1B-19K. For unbiased
      proteomic analysis of proteins targeted by BCL-xL in adenovirus-infected cells
      and to visualize the interactions with target proteins, BCL-xL was targeted to
      cytosolic inclusion bodies utilizing the orthoreovirus uNS protein sequences. The
      chimeric protein was localized in non-canonical cytosolic factory-like sites and
      promoted survival of virus-infected cells. The BCL-xL-associated proteins were
      isolated from the cytosolic inclusion bodies in adenovirus-infected cells and
      analyzed by LC-MS. These proteins included BAX, BAK, BID, BIK and BIM as well as
      mitochondrial proteins such as prohibitin 2, ATP synthase and DNA-PKcs. Our
      studies suggested that in addition to the interaction with various pro-apoptotic
      proteins, the association with certain mitochondrial proteins such as DNA-PKcs
      and prohibitins might augment the survival function of BCL-xL in virus infected
      cells. 

PMID- 25965793
TI  - Genomic characterization of emergent pseudorabies virus in China reveals marked
      sequence divergence: Evidence for the existence of two major genotypes.
AB  - Recently pseudorabies outbreaks have occurred in many vaccinated farms in China.
      To identify genetic characteristics of pseudorabies virus (PRV) strains, we
      obtained the genomic sequences of PRV strains HeN1 and JS, which were compared to
      4 PRV genomes and 729 partial gene sequences. PRV strains isolated in China
      showed marked sequence divergence compared to European and American strains.
      Phylogenetic analysis revealed that for the first time PRV can be divided into 2
      distinct clusters, with Chinese strains being genotype II and PRVs isolated from
      other countries being genotype I. Restriction fragment length polymorphism
      analysis confirmed differences between HeN1 and Bartha strains, as did the
      presence of unique insertion/deletion polymorphisms and microsatellites. This
      divergence between the two genotypes may have been generated from long-term,
      independent evolution, which could also explain the low efficacy of the Bartha
      vaccine in protecting pigs infected with genotype II PRV. 

PMID- 25965794
TI  - Roles of Epstein-Barr virus BGLF3.5 gene and two upstream open reading frames in
      lytic viral replication in HEK293 cells.
AB  - The Epstein-Barr virus (EBV) predominantly establishes a latent infection in B
      lymphocytes, but a small percentage of infected cells switch from the latent
      state to the lytic cycle, leading to potent viral DNA replication and progeny
      viruses production. We here focused on a lytic gene BGLF3.5, and first
      established BGLF3.5 mutants by marker cassette insertion. Unexpectedly, this
      insertion mutant failed to produce BGLF4 protein and thus progeny production was
      severely inhibited. Then we carefully made two point mutant viruses (stop codon
      insertion or frame-shift mutation) and found that BGLF3.5 is not essential for
      EBV lytic replication processes, such as viral gene expression, DNA replication,
      or progeny production in the HEK293 cells although its homolog in murine
      gammaherpesvirus 68 (MHV-68) was reported to be essential. In addition, we
      examined the roles of two short, upstream open reading frames within the 5'UTR of
      BGLF3.5 gene in translation of BGLF4. 

PMID- 25965795
TI  - Identification of amino-acid residues in the V protein of peste des petits
      ruminants essential for interference and suppression of STAT-mediated interferon
      signaling.
AB  - Peste des petits ruminants virus (PPRV) causes a fatal disease in small
      ruminants. V protein of PPRV plays a pivotal role in interfering with host innate
      immunity by blocking IFNs signaling through interacting with STAT1 and STAT2. In
      the present study, the results demonstrated that PPRV V protein blocks IFN
      actions in a dose dependent manner and restrains the translocation of STAT1/2
      proteins. We speculate that the translocation inhibition might be caused by the
      interfering of the downstream of STAT protein. Mutagenesis defines that Cys
      cluster and Trp motif of PPRV V protein are essential for STAT-mediated IFN
      signaling. These findings give a new sight for the further studies to understand
      the delicate mechanism of PPRV to escape the IFN signaling. 

PMID- 25965796
TI  - Prevalence of Pf1-like (pro)phage genetic elements among Pseudomonas aeruginosa
      isolates.
AB  - Pf1-like bacteriophages (family Inoviridae) of Pseudomonas aeruginosa can
      contribute to bacterial short term evolution and virulence. Here we examine Pf1
      like (pro)phage diversity and prevalence among different P. aeruginosa isolates.
      Pf1-like prophages in sequenced genomes of P. aeruginosa were analyzed and
      grouped into four clades: Pf4, Pf5, Pf7 and Pf-LES. P. aeruginosa strains (n=241)
      were screened for the presence of universal (primers PfUa and PfUb) and specific
      Pf1-like genetic elements (Pf1, Pf4 and Pf5). More than half of the strains
      contained at least one Pf1-like genetic element (60%); universal elements were
      detected in 56% of the strains, Pf4 in 22%, Pf1 in 18% and Pf5 in 7%. Infectivity
      experiments confirmed that strains yielding PCR products with either universal or
      Pf4 specific primers can release infective virions. Based on the high prevalence
      of Pf1-like (pro)phages, it is necessary to further examine their involvement in
      P. aeruginosa virulence. 

PMID- 25965797
TI  - Contribution of N-linked glycans on HSV-2 gB to cell-cell fusion and viral entry.
AB  - HSV-2 is the major cause of genital herpes and its infection increases the risk
      of HIV-1 acquisition and transmission. HSV-2 glycoprotein B together with
      glycoproteins D, H and L are indispensable for viral entry, of which gB, as a
      class III fusogen, plays an essential role. HSV-2 gB has seven potential N-linked
      glycosylation (N-CHO) sites, but their significance has yet to be determined. For
      the first time, we systematically analyzed the contributions of N-linked glycans
      on gB to cell-cell fusion and viral entry. Our results demonstrated that, of the
      seven potential N-CHO sites on gB, mutation at N390, N483 or N668 decreased cell
      cell fusion and viral entry, while mutation at N133 mainly affected protein
      expression and the production of infectious virus particles by blocking the
      transport of gB from the endoplasmic reticulum to Golgi. Our findings highlight
      the significance of N-linked glycans on HSV-2 gB expression and function. 

PMID- 25965798
TI  - The human cytomegalovirus lytic cycle is induced by 1,25-dihydroxyvitamin D3 in
      peripheral blood monocytes and in the THP-1 monocytic cell line.
AB  - Human cytomegalovirus (HCMV) resides in a latent form in hematopoietic
      progenitors and undifferentiated cells within the myeloid lineage. Maturation and
      differentiation along the myeloid lineage triggers lytic replication. Here, we
      used peripheral blood monocytes and the monocytic cell line THP-1 to investigate
      the effects of 1,25-dihydroxyvitamin D3 on HCMV replication. Interestingly, 1,25
      dihydroxyvitamin D3 induces lytic replication marked by upregulation of HCMV gene
      expression and production of infectious virus. Moreover, we demonstrate that the
      effects of 1,25-dihydroxyvitamin D3 correlate with maturation/differentiation of
      the monocytes and not by directly stimulating the MIEP. These results are
      somewhat surprising as 1,25-dihydroxyvitamin D3 typically boosts immunity to
      bacteria and viruses rather than driving the infectious life cycle as it does for
      HCMV. Defining the signaling pathways kindled by 1,25-dihydroxyvitamin D3 will
      lead to a better understanding of the underlying molecular mechanisms that
      determine the fate of HCMV once it infects cells in the myeloid lineage. 

PMID- 25965800
TI  - Upstream binding factor inhibits herpes simplex virus replication.
AB  - Herpes simplex virus 1 (HSV-1) infection induces changes to the host cell nucleus
      including relocalization of the cellular protein Upstream Binding Factor (UBF)
      from the nucleolus to viral replication compartments (VRCs). Herein, we tested
      the hypothesis that UBF is recruited to VRCs to promote viral DNA replication.
      Surprisingly, infection of UBF-depleted HeLa cells with HSV-1 or HSV-2 produced
      higher viral titers compared to controls. Reduced expression of UBF also led to a
      progressive increase in the relative amount of HSV-1 DNA versus controls, and
      increased levels of HSV-1 ICP27 and TK mRNA and protein, regardless of whether
      viral DNA replication was inhibited or not. Our results suggest that UBF can
      inhibit gene expression from viral DNA prior to its replication. A similar but
      smaller effect on viral titers was observed in human foreskin fibroblasts. This
      is the first report of UBF having a restrictive effect on replication of a virus.

PMID- 25965799
TI  - Proteomic analysis reveals down-regulation of surfactant protein B in murine type
      II pneumocytes infected with influenza A virus.
AB  - Infection of type II alveolar epithelial (ATII) cells by influenza A viruses
      (IAV) correlates with severe respiratory disease in humans and mice. To
      understand pathogenic mechanisms during IAV infection of ATII cells, murine ATII
      cells were cultured to maintain a differentiated phenotype, infected with IAV
      PR8, which causes severe lung pathology in mice, and proteomics analyses were
      performed using liquid chromatography-mass spectrometry. PR8 infection increased
      levels of proteins involved in interferon signaling, antigen presentation, and
      cytoskeleton regulation. Proteins involved in mitochondrial membrane
      permeability, energy metabolism, and chromatin formation had reduced levels in
      PR8-infected cells. Phenotypic markers of ATII cells in vivo were identified,
      confirming the differentiation status of the cultures. Surfactant protein B had
      decreased levels in PR8-infected cells, which was confirmed by immunoblotting and
      immunofluorescence assays. Analysis of ATII cell protein profiles will elucidate
      cellular processes in IAV pathogenesis, which may provide insight into potential
      therapies to modulate disease severity. 

PMID- 25965801
TI  - An anti-G protein monoclonal antibody treats RSV disease more effectively than an
      anti-F monoclonal antibody in BALB/c mice.
AB  - Respiratory syncytial virus (RSV) belongs to the family Paramyxoviridae and is
      the single most important cause of serious lower respiratory tract infections in
      young children, yet no highly effective treatment or vaccine is available. To
      clarify the potential for an anti-G mAb, 131-2G which has both anti-viral and
      anti-inflammatory effects, to effectively treat RSV disease, we determined the
      kinetics of its effect compared to the effect of the anti-F mAb, 143-6C on
      disease in mice. Treatment administered three days after RSV rA2-line19F (r19F)
      infection showed 131-2G decreased breathing effort, pulmonary mucin levels,
      weight loss, and pulmonary inflammation earlier and more effectively than
      treatment with mAb 143-6C. Both mAbs stopped lung virus replication at day 5 post
      infection. These data show that, in mice, anti-G protein mAb is superior to
      treating disease during RSV infection than an anti-F protein mAb similar to
      Palivizumab. This combination of anti-viral and anti-inflammatory activity makes
      131-2G a promising candidate for treating for active human RSV infection. 

PMID- 25965803
TI  - Framework for resilience in material supply chains, with a case study from the
      2010 Rare Earth Crisis.
AB  - In 2010, Chinese export restrictions caused the price of the rare earth element
      neodymium to increase by a factor of 10, only to return to almost normal levels
      in the following months. This despite the fact that the restrictions were not
      lifted. The significant price peak shows that this material supply chain was only
      weakly resistant to a major supply disruption. However, the fact that prices
      rapidly returned to lower levels implies a certain resilience. With the help of a
      novel approach, based on resilience theory combined with a material flow analysis
      (MFA) based representation of the neodymium magnet (NdFeB) supply chain, we show
      that supply chain resilience is composed of various mechanisms, including (a)
      resistance, (b) rapidity, and (c) flexibility, that originate from different
      parts of the supply chain. We make recommendations to improve the capacity of the
      NdFeB system to deal with future disruptions and discuss potential generalities
      for the resilience of other material supply chains. 

PMID- 25965802
TI  - An unexpected inhibition of antiviral signaling by virus-encoded tumor suppressor
      p53 in pancreatic cancer cells.
AB  - Virus-encoded tumor suppressor p53 transgene expression has been successfully
      used in vesicular stomatitis virus (VSV) and other oncolytic viruses (OVs) to
      enhance their anticancer activities. However, p53 is also known to inhibit virus
      replication via enhanced type I interferon (IFN) antiviral responses. To examine
      whether p53 transgenes enhance antiviral signaling in human pancreatic ductal
      adenocarcinoma (PDAC) cells, we engineered novel VSV recombinants encoding human
      p53 or the previously described chimeric p53-CC, which contains the coiled-coil
      (CC) domain from breakpoint cluster region (BCR) protein and evades the dominant
      negative activities of endogenously expressed mutant p53. Contrary to an expected
      enhancement of antiviral signaling by p53, our global analysis of gene expression
      in PDAC cells showed that both p53 and p53-CC dramatically inhibited type I IFN
      responses. Our data suggest that this occurs through p53-mediated inhibition of
      the NF-kappaB pathway. Importantly, VSV-encoded p53 or p53-CC did not inhibit
      antiviral signaling in non-malignant human pancreatic ductal cells, which
      retained their resistance to all tested VSV recombinants. To the best of our
      knowledge, this is the first report of p53-mediated inhibition of antiviral
      signaling, and it suggests that OV-encoded p53 can simultaneously produce
      anticancer activities while assisting, rather than inhibiting, virus replication
      in cancer cells. 

PMID- 25965805
TI  - The three-legged stool: linkages among education, research, and practice in
      gerontology and geriatrics. Foreword.

PMID- 25965804
TI  - Discovery of 1-(3,3-dimethylbutyl)-3-(2-fluoro-4-methyl-5-(7-methyl-2
      (methylamino)pyrido[2,3-d]pyrimidin-6-yl)phenyl)urea (LY3009120) as a pan-RAF
      inhibitor with minimal paradoxical activation and activity against BRAF or RAS
      mutant tumor cells.
AB  - The RAS-RAF-MEK-MAPK cascade is an essential signaling pathway, with activation
      typically mediated through cell surface receptors. The kinase inhibitors
      vemurafenib and dabrafenib, which target oncogenic BRAF V600E, have shown
      significant clinical efficacy in melanoma patients harboring this mutation.
      Because of paradoxical pathway activation, both agents were demonstrated to
      promote growth and metastasis of tumor cells with RAS mutations in preclinical
      models and are contraindicated for treatment of cancer patients with BRAF WT
      background, including patients with KRAS or NRAS mutations. In order to eliminate
      the issues associated with paradoxical MAPK pathway activation and to provide
      therapeutic benefit to patients with RAS mutant cancers, we sought to identify a
      compound not only active against BRAF V600E but also wild type BRAF and CRAF. On
      the basis of its superior in vitro and in vivo profile, compound 13 was selected
      for further development and is currently being evaluated in phase I clinical
      studies. 

PMID- 25965806
TI  - Type 1 and type 2 diabetes and cancer mortality in the 2002-2009 cohort of 39,811
      French dialyzed patients.
AB  - End-stage renal disease is a chronic and progressive pathology associated with
      several comorbidities, particularly diabetes. Indeed, diabetes is the first cause
      of end-stage renal disease and, in France, 42% of incident patients had diabetes
      in 2012. In the general population, diabetes is associated with increased cancer
      risk. The aim of this study was to examine the association between risk of cancer
      death and diabetes in a large French cohort of patients with end-stage renal
      disease. Data on all patients with end-stage renal disease who initiated dialysis
      in France between 2002 and 2009 were extracted from the Renal Epidemiology
      Information Network registry. The risk of dying by cancer was studied using the
      Fine and Gray model to take into account the competing risk of death by other
      causes. We analyzed 39,811 patients with end-stage renal disease. Their mean age
      was 67.7+/-15 years, 39.4% had diabetes and 55.3% at least one cardiovascular
      disease. Compared with the non-diabetic group, patients with diabetes were older
      and had more cardiovascular and respiratory comorbidities when they started
      dialysis. Conversely, fewer diabetic patients had also a tumor at the beginning
      of the renal replacement therapy. Cancer was indicated as the cause of death for
      6.7% of diabetic and 13.4% of non-diabetic patients. The Fine and Gray
      multivariate analyses indicated that diabetes (HR=0.72 95% CI: [0.68-0.95],
      p<0.001) and also female gender, peritoneal dialysis, cardio-vascular disease and
      kidney transplantation were associated with decreased risk of death by cancer. In
      this French cohort of patients with end-stage renal disease, diabetes was not
      associated with a significant increased risk of dying from cancer. Studies on the
      incidence of cancer in patients with ESRD are now needed to evaluate the
      potential association between diabetes and specific malignancies in this
      population.

PMID- 25965807
TI  - Global registration of subway tunnel point clouds using an augmented extended
      Kalman filter and central-axis constraint.
AB  - Because tunnels generally have tubular shapes, the distribution of tie points
      between adjacent scans is usually limited to a narrow region, which makes the
      problem of registration error accumulation inevitable. In this paper, a global
      registration method is proposed based on an augmented extended Kalman filter and
      a central-axis constraint. The point cloud registration is regarded as a
      stochastic system, and the global registration is considered to be a process that
      recursively estimates the rigid transformation parameters between each pair of
      adjacent scans. Therefore, the augmented extended Kalman filter (AEKF) is used to
      accurately estimate the rigid transformation parameters by eliminating the error
      accumulation caused by the pair-wise registration. Moreover, because the scanning
      range of a terrestrial laser scanner can reach hundreds of meters, a single scan
      can cover a tunnel segment with a length of more than one hundred meters, which
      means that the central axis extracted from the scan can be employed to control
      the registration of multiple scans. Therefore, the central axis of the subway
      tunnel is first determined through the 2D projection of the tunnel point cloud
      and curve fitting using the RANSAC (RANdom SAmple Consensus) algorithm. Because
      the extraction of the central axis by quadratic curve fitting may suffer from
      noise in the tunnel points and from variations in the tunnel, we present a global
      extraction algorithm that is based on segment-wise quadratic curve fitting. We
      then derive the central-axis constraint as an additional observation model of
      AEKF to optimize the registration parameters between each pair of adjacent scans.
      The proposed approach is tested on terrestrial point clouds that were acquired in
      a subway tunnel. The results show that the proposed algorithm is capable of
      improving the accuracy of aligning multiple scans by 48%. 

PMID- 25965808
TI  - Association of Ficolin-2 Serum Levels and FCN2 Genetic Variants with Indian
      Visceral Leishmaniasis.
AB  - BACKGROUND: Visceral leishmaniasis (VL), one of the neglected tropical diseases,
      is endemic in the Indian subcontinent. Ficolins are circulating serum proteins of
      the lectin complement system and involved in innate immunity. METHODS: We have
      estimated ficolin-2 serum levels and analyzed the functional variants of the
      encoding gene FCN2 in 218 cases of VL and in 225 controls from an endemic region
      of India. RESULTS: Elevated levels of serum ficolin-2 were observed in VL cases
      compared to the controls (adjusted P<0.0001). The genetic analysis revealed that
      the FCN2 structural variant +6359 C>T (p.T236M) was associated with VL (OR=2.2,
      95% CI=1.23-7.25, P=0.008) and with high ficolin-2 serum levels. We also found
      that the FCN2*AAAC haplotype occurred more frequently among healthy controls when
      compared to cases (OR=0.59, 95%CI=0.37-0.94, P=0.023). CONCLUSIONS: Our findings
      indicate that the FCN2 variant +6359C>T is associated with the occurrence of VL
      and that ficolin-2 serum levels are elevated in Leishmania infections.

PMID- 25965809
TI  - Are Qualitative Assessments of Background Parenchymal Enhancement, Amount of
      Fibroglandular Tissue on MR Images, and Mammographic Density Associated with
      Breast Cancer Risk?
AB  - PURPOSE: To investigate whether qualitative magnetic resonance (MR) imaging
      assessments of background parenchymal enhancement (BPE), amount of fibroglandular
      tissue (FGT), and mammographic density are associated with risk of developing
      breast cancer in women who are at high risk. MATERIALS AND METHODS: In this
      institutional review board-approved HIPAA-compliant retrospective study, all
      screening breast MR images obtained from January 2006 to December 2011 in women
      aged 18 years or older and at high risk for but without a history of breast
      cancer were identified. Women in whom breast cancer was diagnosed after index MR
      imaging comprised the cancer cohort, and one-to-one matching (age and BRCA
      status) of each woman with breast cancer to a control subject was performed by
      using MR images obtained in women who did not develop breast cancer with follow
      up time maximized. Amount of BPE, BPE pattern (peripheral vs central), amount of
      FGT at MR imaging, and mammographic density were assessed on index images.
      Imaging features were compared between cancer and control cohorts by using
      conditional logistic regression. RESULTS: Twenty-three women at high risk (mean
      age, 47 years +/- 10 [standard deviation]; six women had BRCA mutations) with no
      history of breast cancer underwent screening breast MR imaging; in these women, a
      diagnosis of breast cancer (invasive, n = 12; in situ, n = 11) was made during
      the follow-up interval. Women with mild, moderate, or marked BPE were nine times
      more likely to receive a diagnosis of breast cancer during the follow-up interval
      than were those with minimal BPE (P = .007; odds ratio = 9.0; 95% confidence
      interval: 1.1, 71.0). BPE pattern, MR imaging amount of FGT, and mammographic
      density were not significantly different between the cohorts (P = .5, P = .5, and
      P = .4, respectively). CONCLUSION: Greater BPE was associated with a higher
      probability of developing breast cancer in women at high risk for cancer and
      warrants further study.

PMID- 25965810
TI  - Children's Headache: Drawings in the Diagnostic Work Up.
AB  - OBJECTIVES: This study aims to evaluate the drawings effectiveness in childhood
      headache assessment. BACKGROUND: Headache is a common cause of pain in children.
      Although drawings have been used in childhood to recognize psychological insights
      and pain perception, they were rarely used for headache characterization.
      METHODS: We collected drawings from 67 subjects with cephalalgia during a 22
      month timeframe. The clinical diagnosis was made according to the 2nd edition of
      The International Headache Classification. Drawings were independently
      categorized as migraine or tension-type headache (TTH) by two child
      neuropsychiatrists blinded to the clinical data. Cohen kappa for interrater
      agreement, sensitivity, specificity, and positive predictive value (PPV) were
      calculated. Subjects were also divided into three age groups to assess the
      influence of age. Finally, a control group of 90 subjects was collected and K
      means cluster analysis was performed. RESULTS: The drawings had a sensitivity of
      85.71 and 81.48%, a specificity of 81.48 and 85.71%, and a PPV of 85.71 and
      81.48%, for migraine and TTH diagnosis, respectively. Drawings by the older age
      group showed the highest predictability degree. Finally, by mean of cluster
      analysis, 59 of the 67 patients were correctly classified, whereas control
      subjects were similarly distributed between the two clusters. CONCLUSIONS:
      Drawings are a useful instrument for migraine and TTH differential diagnosis.
      Thus, we suggest their inclusion in childhood headache diagnostic assessment.

PMID- 25965811
TI  - Sleep and epilepsy syndromes.
AB  - Sleep and epilepsy have a close relationship. About 20% of patients suffer
      seizures only during the night, approximately 40% only during the day and
      approximately 35% during the day and night. In certain epilepsy syndromes, the
      occurrence of seizures is strongly related to sleep or awakening. Infantile
      spasms appear predominately on awakening, and hypsarrhythmia is sometimes visible
      only in sleep. Children with Panayiotopoulos syndrome or benign epilepsy with
      centrotemporal spikes (BECTS) have seizures mostly when asleep, and in both
      syndromes interictal spike waves are markedly accentuated in slow wave sleep.
      Electrical status epilepticus during slow sleep/continuous spike wave discharges
      during sleep (ESES/CSWS), atypical benign partial epilepsy, and Landau-Kleffner
      syndrome are epileptic encephalopathies with substantial behavioral and cognitive
      deficits, various seizures, and continuous spike-wave activity during non-rapid
      eye movement (NREM) sleep. The hallmark of juvenile myoclonic epilepsy and grand
      mal seizures on awakening are seizure symptoms within 2 hours after awakening,
      often provoked by sleep deprivation. Nocturnal frontal lobe epilepsy is sometimes
      mistaken for parasomnia. Differentiation is possible when the clinical symptoms
      and the frequency of the paroxysmal events per night and month are carefully
      observed and nocturnal video electroencephalography (EEG) performed. Sleep EEG
      recordings may be helpful in patients with suspected epilepsy and nonconclusive
      awake EEG. Depending on the clinical question, sleep recordings should be
      performed during nap (natural sleep or drug induced), during the night, or after
      sleep deprivation. 

PMID- 25965813
TI  - Universal bound on the Fano factor in enzyme kinetics.
AB  - The Fano factor, an observable quantifying fluctuations of product generation by
      a single enzyme, can reveal information about the underlying reaction scheme. A
      lower bound on this Fano factor that depends on the thermodynamic affinity
      driving the transformation from substrate to product constrains the number of
      intermediate states of an enzymatic cycle. So far, this bound has been proven
      only for a unicyclic network of states. We show that the bound can be extended to
      arbitrary multicyclic networks, with the Fano factor constraining the largest
      value of the effective length, which is the ratio between the number of states
      and the number of products, among all cycles. 

PMID- 25965812
TI  - A point mutation in the extracellular domain of KIT promotes tumorigenesis of
      mast cells via ligand-independent auto-dimerization.
AB  - Mutations in the juxtamembrane and tyrosine kinase domains of the KIT receptor
      have been implicated in several cancers and are known to promote tumorigenesis.
      However, the pathophysiological manifestations of mutations in the extracellular
      domain remain unknown. In this study, we examined the impact of a mutation in the
      extracellular domain of KIT on mast cell tumorigenesis. A KIT mutant with an
      Asn508Ile variation (N508I) in the extracellular domain derived from a canine
      mast cell tumor was introduced into IC-2 cells. The IC-2(N508I) cells
      proliferated in a cytokine-independent manner and showed KIT auto
      phosphorylation. Subcutaneous injection of IC-2(N508I) cells into the dorsal area
      of immunodeficient BALB/c-nu/nu mice resulted in the formation of solid tumors,
      but tumor progression was abrogated by treatment with a tyrosine kinase inhibitor
      (STI571). In addition, the N508I mutant KIT protein dimerized in the absence of
      the natural ligand, stem cell factor. Structure modeling indicates that the
      increased hydrophobicity of the mutant led to the stabilization of KIT dimers.
      These results suggest that this extracellular domain mutation confers a ligand
      independent tumorigenic phenotype to mast cells by KIT auto-dimerization that is
      STI571-sensitive. This is the first report demonstrating the tumorigenic
      potential of a mutation in the extracellular domain of KIT. 

PMID- 25965814
TI  - Electron Probe Microanalysis: A Review of the Past, Present, and Future.
AB  - The 50th anniversary of the application of electron probe microanalysis (EPMA) to
      the Earth Sciences provides an opportunity for an assessment of the state-of-the
      art of the technique. Stemming from the introduction of the first automated
      instruments, the latest developments of EPMA and some typical applications are
      reviewed with an eye to the future. The most noticeable recent technical
      achievements such as the field-emission electron gun, the latest generation of
      energy and wavelength dispersive spectrometers, and the development of analytical
      methods based on new sets of first principle data obtained by the use of
      sophisticated computer codes, allow for the extension of the method to the
      analysis of trace elements, ultra-light elements (down to Li), small particles,
      and thin films, with a high degree of accuracy and precision and within a
      considerably reduced volume of interaction. A number of working examples and a
      thorough list of references provide the reader with a working knowledge of the
      capabilities and limitations of EPMA today. 

PMID- 25965815
TI  - Gamma delta T-cell large granular lymphocyte lymphoma in a dog.
AB  - A 2-year and 6-month-old female neutered Labrador Retriever with Horner syndrome,
      megaesophagus, and a mediastinal mass was referred to the Queen Mother Hospital
      for Animals of the Royal Veterinary College. A large granular lymphocyte (LGL)
      lymphoma was diagnosed on cytology; flow cytometric analysis revealed a
      gammadelta T-cell phenotype (CD3+, CD5+, CD45+, TCRgammadelta+, CD4-, CD8-, CD34
      , CD21-). Chemotherapy was started with a combination of lomustine, vincristine,
      procarbazine, and prednisolone, followed by bleyomicin. Euthanasia was elected by
      the owners, due to progressive deterioration and lack of quality of life, 28 days
      after diagnosis. This is the first cytologic and immunophenotypic
      characterization of a canine gammadelta T-cell lymphoma with LGL morphology and
      probably of mediastinal origin. The role of chemotherapy in delaying the disease
      progression remains unknown. 

PMID- 25965816
TI  - Effects of different levels of intraocular stray light on kinetic perimetry
      findings.
AB  - PURPOSE: To evaluate the effect of different levels of intraocular stray light on
      kinetic perimetry findings. METHODS: Twenty-five eyes of 25 healthy young
      participants were examined by automated kinetic perimetry (Octopus 900) using
      Goldmann stimuli III4e, I4e, I3e, I2e, and I1e. Each stimulus was presented with
      a velocity of 3 degrees /s at 24 meridians with 15 degrees  intervals. Four
      levels of intraocular stray light were induced using non-white opacity filter
      (WOF) filters and WOFs applied to the clear plastic eye covers of the
      participants. The visual acuity, pupil diameter, isopter area, and kinetic
      sensitivity of each meridian were analyzed for each WOF density. RESULTS: Visual
      acuity deteriorated with increasing WOF densities (p < 0.01). With a visual
      acuity of 0.1 LogMAR units, the isopter areas for III4e, I4e, I3e, I2e, and I1e
      decreased by -32.7 degree2 (-0.2%), -255.7 degree2 (-2.6%), -381.2 degree2 (
      6.2%), -314.8 degree2 (-12.8%), and -59.2 degree2 (-15.2%), respectively; kinetic
      sensitivity for those stimuli decreased by -0.1 degree (-0.1%), -0.8 degree (
      1.4%), -1.6 degree (-3.7%), -2.7 degree (-9.7%), and -1.7 degree (-16.2%),
      respectively. The pupil diameter with each WOF density was not significantly
      different. CONCLUSION: Kinetic perimetry measurements with a high-intensity
      stimulus (i.e., III4e) were unaffected by intraocular stray light. In contrast,
      measurements with the I4e, I3e, I2e, and I1e stimuli, especially I2e and I1e,
      were affected. Changes in the shape of the isopter resulting from opacity must be
      monitored, especially in cases of smaller and lower-intensity stimuli.

PMID- 25965817
TI  - MiR-361-5p inhibits colorectal and gastric cancer growth and metastasis by
      targeting staphylococcal nuclease domain containing-1.
AB  - MicroRNAs (miRs) function as key regulators of gene expression and their
      deregulation is associated with the carcinogenesis of various cancers. In the
      present study, we investigated the biological role and mechanism of miR-361-5p in
      colorectal carcinoma (CRC) and gastric cancer (GC). We showed that microRNA-361
      5p (miR-361-5p) was down-regulated in CRC and GC in comparison to the controls.
      Meanwhile, the expression levels of miR-361-5p negatively correlated with lung
      metastasis and prognosis in clinical CRC patients. Overexpression of miR-361-5p
      markedly suppressed proliferation, migration and invasion of cancer cells.
      Additionally, this phenotype could be partially rescued by the ectopic expression
      of staphylococcal nuclease domain containing-1 (SND1). SND1 was identified as a
      target of miR-361-5p using bioinformatics analysis and in vitro luciferase
      reporter assays. In turn, SND1 bound to pre-miR-361-5p and suppressed the
      expression of miR-361-5p, thus exerting a feedback loop. Most interestingly, in
      vivo studies showed that restoration of miR-361-5p significantly inhibited tumor
      growth and especially the lung metastasis in nude mice. Therefore, it could be
      concluded that miR-361-5p functions as a tumor-suppressive miRNA through directly
      binding to SND1, highlighting its potential as a novel agent for the treatment of
      patients with CRC and GC.

PMID- 25965818
TI  - ERK5 negatively regulates tobacco smoke-induced pulmonary epithelial-mesenchymal
      transition.
AB  - As the primary cause of lung cancer, tobacco smoke (TS) promotes the initiation
      and progression of lung tumorigenesis. Epithelial-mesenchymal transition (EMT) is
      a crucial process involved in cell malignant transformation. The role of ERK5,
      the lesser studied member of MAPKs family, in regulating TS-triggered pulmonary
      EMT has not been investigated. Normal human bronchial epithelial cells and BALB/c
      mice were used as in vitro and in vivo TS exposure models. Exposure of normal
      human bronchial epithelial cells to TS for 7 days induced morphological change,
      enhanced migratory and invasive capacities, reduced epithelial marker expression
      and increased mesenchymal marker expression. Importantly, we demonstrated for the
      first time that ERK5 negatively regulated TS-mediated lung epithelial EMT, as
      evidenced by the findings that TS suppressed ERK5 activation, and that TS
      triggered EMT was mimicked with ERK5 inhibition and reversed by ERK5
      overexpression. The negative regulation of ERK5 on pulmonary EMT was further
      confirmed in mice exposed to TS for 12 weeks. Taken together, our data suggest
      that ERK5 negatively regulates TS-mediated pulmonary EMT. These findings provide
      new insight into the molecular mechanisms of TS-associated lung tumorigenesis and
      may open up new avenues in the search for potential target of lung cancer
      intervention. 

PMID- 25965819
TI  - Chronic exposure to cerebrospinal fluid of multiple system atrophy in
      neuroblastoma and glioblastoma cells induces cytotoxicity via ER stress and
      autophagy activation.
AB  - Oncogenesis and neurodegeneration share many common pathogenic pathways, involved
      in endoplastic reticulum (ER) stress, autophagy, DNA repair, and oxidative
      stress. However, mechanisms of cross-talking between oncogenesis and
      neurodegeneration are still unknown. Characterized by abnormal accumulation of
      alpha-synuclein (alpha-syn) aggregates in central nervous system (CNS), multiple
      system atrophy (MSA) is classified as alpha-synucleinopathy. Rapidly emerging
      evidence suggests that 'prion-like propagation' of alpha-syn aggregates in the
      regional spread of CNS leads to the progression of alpha-synucleinopathy. Whether
      cerebrospinal fluid (CSF) has deteriorating effects on neurogenic tumor cells and
      is involved in progression of alpha-synucleinopathy has not been explored. Here,
      we first show the cytotoxic effects of MSA-CSF on the neuroblastoma and
      glioblastoma cells and its underlying mechanism in vitro. Remarkably, MSA-CSF
      induced cytotoxicity via activating ER stress-associated apoptosis and autophagy
      in both SH-SY5Y and U251 cells. The result from in vivo systematic
      neuropathological analysis reveals that abnormally activated ER stress and
      autophagy were confined to substantia nigra and cerebellum in mouse CNS following
      MSA-CSF treatment. Specifically, dopamine neurons in substantia nigra and
      Purkinje cells in cerebellum cortex were degenerated in MSA-CSF-injected mice.
      Altogether, these findings demonstrate that MSA-CSF exerts cytotoxicities on
      nervous system neoplasms and accelerates the progression of synucleinopathies. 

PMID- 25965820
TI  - Does beer, wine or liquor consumption correlate with the risk of renal cell
      carcinoma? A dose-response meta-analysis of prospective cohort studies.
AB  - Despite plenty of evidence supports an inverse association between alcohol
      drinking and risk of renal cell carcinoma (RCC), sex-specific and beverage
      specific dose-response relationships have not been well established. We examined
      this association by performing a systematic review and meta-analysis of
      prospective studies. Studies were identified by comprehensively searching PubMed
      and EMBASE databases through February 21, 2015. Categorical and dose-response
      meta-analyses were conducted to identify the effects of alcohol on RCC. A total
      of eight publications (including seven cohort studies and one pooled analysis of
      12 cohort studies) were eligible for this meta-analysis. Dose-response analysis
      showed that each 5 g/day increment of alcohol intake corresponded to a 5%
      decrease in risk of RCC for males and 9% for females. Alcohol intakes from wine,
      beer, and liquor were each associated with a reduced risk of RCC. When these
      associations were examined separately by gender, statistically significant
      inverse associations were restricted to alcohol from wine among females (RR =
      0.82, 95% CI 0.73-0.91) and to alcohol from beer and from liquor among males (RR
      = 0.87, 95% CI 0.83-0.91 and RR = 0.95, 95% CI 0.92-0.99, respectively). In
      conclusion, there exist gender-specific and beverage-specific differences in the
      association between alcohol intake and RCC risk. 

PMID- 25965822
TI  - Prognostic value of MET protein overexpression and gene amplification in
      locoregionally advanced nasopharyngeal carcinoma.
AB  - This study assessed the incidence and prognostic value of MET protein
      overexpression and gene amplification in locoregionally advanced nasopharyngeal
      carcinoma (NPC). Specimens from 376 consecutive patients with locoregionally
      advanced NPC were subjected to immunohistochemistry to analyze MET protein
      expression and fluorescence in situ hybridization to assess MET amplification
      status. In total, 139/376 (37.0%) patients had MET protein overexpression; of
      whom, 7/139 (5.0%) had MET amplification. MET overexpression was significantly
      associated with locoregional failure (P = 0.009), distant metastasis (P = 0.006)
      and death (P < 0.001); MET amplification was significantly associated with death
      (P = 0.021). A positive correlation was observed between MET copy number status
      and MET protein expression (r = 0.629, P < 0.001). Multivariate analysis
      demonstrated MET overexpression was an independent prognostic factor for overall
      survival (OS; HR, 1.99; 95% CI, 1.38-2.87; P < 0.001) and disease-free survival
      (DFS; HR, 1.85; 95% CI, 1.33-2.57; P < 0.001), and MET amplification was
      independently associated with poorer OS (HR, 4.24; 95% CI, 1.78-10.08; P < 0.001)
      and DFS (HR, 5.44; 95% CI, 2.44-12.09; P < 0.001). In conclusion, MET protein
      overexpression and gene amplification are independent prognostic factors for OS
      and DFS in locoregionally advanced nasopharyngeal carcinoma, and may provide
      therapeutic biomarkers to identify patients in whom MET inhibitors may be
      beneficial. 

PMID- 25965823
TI  - Intelectin 1 suppresses tumor progression and is associated with improved
      survival in gastric cancer.
AB  - Recent evidence shows the emerging roles of intelectin 1 (ITLN1), a secretory
      lectin, in human cancers. Our previous studies have implicated the potential
      roles of ITLN1 in the aggressiveness of gastric cancer. Herein, we investigated
      the functions, downstream targets, and clinical significance of ITLN1 in the
      progression of gastric cancer. We demonstrated that ITLN1 increased the levels of
      hepatocyte nuclear factor 4 alpha (HNF4alpha), resulting in suppression of
      nuclear translocation and transcriptional activity of beta-catenin in gastric
      cancer cells. Mechanistically, ITLN1 attenuated the activity of nuclear factor
      kappa B, a transcription factor repressing the HNF4alpha expression, in gastric
      cancer cells through inactivating the phosphoinositide 3-kinase/AKT/Ikappa B
      kinase signaling. Gain- and loss-of-function studies demonstrated that ITLN1
      suppressed the growth, invasion, and metastasis of gastric cancer cells in vitro
      and in vivo. In addition, restoration of HNF4alpha expression prevented the
      gastric cancer cells from ITLN1-mediated changes in these biological features. In
      clinical gastric cancer tissues, HNF4alpha expression was positively correlated
      with that of ITLN1. Patients with high ITLN1 or HNF4alpha expression had greater
      survival probability. Taken together, these data indicate that ITLN1 suppresses
      the progression of gastric cancer through up-regulation of HNF4alpha, and is
      associated with improved survival in patients with gastric cancer.

PMID- 25965824
TI  - MicroRNA-155 promotes bladder cancer growth by repressing the tumor suppressor
      DMTF1.
AB  - MicroRNA-155 (miR-155) is dysregulated in human cancers. In this study, we
      reported that miR-155 was over-expressed in bladder cancer tissues. We found that
      miR-155 promoted cell proliferation in vitro and tumorigenesis in vivo. MiR-155
      directly reduced the expression of the tumor suppressor DMTF1. The expression of
      DMTF1 was decreased in bladder cancer tissues. Similar to the restoring miR-155
      expression, knockdown of DMTF1 promoted cell growth and cell cycle progression,
      whereas DMTF1 over-expression rescued the effect of miR-155. Moreover, we
      investigated DMTF1-Arf-p53 pathway and found that DMTF1 worked in both p53
      dependent and p53-independent manners. Taken together, our findings suggested
      that miR-155 functions as a tumor promoter in bladder cancer, which is partially
      through repressing DMTF1 expression. The identification of miR-155 and its novel
      target DMTF1 will be valuable in developing diagnostic markers and therapeutic
      applications for bladder cancer.

PMID- 25965825
TI  - SLC15A2 genomic variation is associated with the extraordinary response of
      sorafenib treatment: whole-genome analysis in patients with hepatocellular
      carcinoma.
AB  - Reliable biomarkers are required to predict the response to sorafenib. We
      investigated genomic variations associated with responsiveness to sorafenib for
      patients with unresectable hepatocellular carcinoma (HCC). Blood samples from 2
      extreme, 2 strong and 3 poor responders to sorafenib were subjected to whole
      genome analysis. Then, we validated candidate genomic variations with another 174
      HCC patients, and performed in vitro functional analysis and in silico analyses.
      Genomic data of >96 gigabases/sample was generated at average of ~34X sequencing
      depth. In total, 1813 genomic variations were matched to sorafenib responses in
      clinical data; 708 were located within regions for sorafenib-target genes or drug
      absorption, distribution, metabolism, and excretion (ADME)-related genes. From
      them, 36 variants were within the coding regions and 6 identified as non
      synonymous single-nucleotide variants from 4 ADME-related genes (ABCB1, FMO3,
      MUSK, and SLC15A2). Validation genotyping confirmed sequencing results and
      revealed patients genotype for rs2257212 in SLC15A2 showed longer progression
      free survival (HR = 2.18). In vitro study displayed different response to
      sorafenib depending on the genotype of SLC15A2. Structural prediction analysis
      revealed changes of the phosphorylation levels in protein, potentially affecting
      sorafenib-associated enzymatic activity. Our finding using extreme responder
      seems to generate robust biomarker to predict the response of sorafenib treatment
      for HCC.

PMID- 25965826
TI  - Vimentin contributes to epithelial-mesenchymal transition cancer cell mechanics
      by mediating cytoskeletal organization and focal adhesion maturation.
AB  - Modulations of cytoskeletal organization and focal adhesion turnover correlate to
      tumorigenesis and epithelial-mesenchymal transition (EMT), the latter process
      accompanied by the loss of epithelial markers and the gain of mesenchymal markers
      (e.g., vimentin). Clinical microarray results demonstrated that increased levels
      of vimentin mRNA after chemotherapy correlated to a poor prognosis of breast
      cancer patients. We hypothesized that vimentin mediated the reorganization of
      cytoskeletons to maintain the mechanical integrity in EMT cancer cells. By using
      knockdown strategy, the results showed reduced cell proliferation, impaired wound
      healing, loss of directional migration, and increased large membrane extension in
      MDA-MB 231 cells. Vimentin depletion also induced reorganization of cytoskeletons
      and reduced focal adhesions, which resulted in impaired mechanical strength
      because of reduced cell stiffness and contractile force. In addition,
      overexpressing vimentin in MCF7 cells increased cell stiffness, elevated cell
      motility and directional migration, reoriented microtubule polarity, and
      increased EMT phenotypes due to the increased beta1-integrin and the loss of
      junction protein E-cadherin. The EMT-related transcription factor slug was also
      mediated by vimentin. The current study demonstrated that vimentin serves as a
      regulator to maintain intracellular mechanical homeostasis by mediating
      cytoskeleton architecture and the balance of cell force generation in EMT cancer
      cells.

PMID- 25965827
TI  - Correlation between tumor engraftment in patient-derived xenograft models and
      clinical outcomes in colorectal cancer patients.
AB  - Despite numerous studies involving patient-derived xenograft (PDX) models, few
      studies have investigated the relationship between the ability of the tumor to
      engraft (tumorigenicity) and the clinical features of colorectal cancer (CRC).
      The aim of this study was to determine whether tumorigenicity correlates with
      clinical outcomes of CRC patients. We included 241 CRC patients who underwent
      radical surgery from 2010 to 2013. PDX models were established by implanting
      tumor fragments obtained from these patients into the subcutaneous layer of
      immunodeficient mice. Xenografts were successfully established from 62.2%.
      Successful engraftment was associated with advanced stage (p < 0.001) and
      moderate/poor differentiation (p = 0.029). Three-year disease-free survival (DFS)
      rates were lower for patients with tumorigenicity (p = 0.011). In stage III
      patients, tumorigenicity was an independent predictor of poor DFS (p = 0.034). In
      addition, mutation of TP53 was most frequently detected in stage III patients
      with tumorigenicity. Two models of stage IV disease without KRAS mutations showed
      high sensitivity to EGFR-targeted agents, while none of the models with KRAS
      mutations showed high sensitivity. In conclusion, PDX models may provide an
      effective preclinical tool for predicting cancer progression and could be used to
      further genomic and pharmacologic research on personalized treatments.

PMID- 25965828
TI  - Wee1 is required to sustain ATR/Chk1 signaling upon replicative stress.
AB  - The therapeutic efficacy of nucleoside analogues, e.g. gemcitabine, against
      cancer cells can be augmented by inhibitors of checkpoint kinases, including
      Wee1, ATR, and Chk1. We have compared the chemosensitizing effect of these
      inhibitors in cells derived from pancreatic cancer, a tumor entity where
      gemcitabine is part of the first-line therapeutic regimens, and in osteosarcoma
      derived cells. As expected, all three inhibitors rendered cancer cells more
      sensitive to gemcitabine, but Wee1 inhibition proved to be particularly efficient
      in this context. Investigating the reasons for this potent sensitizing effect, we
      found that Wee1 inhibition or knockdown not only blocked Wee1 activity, but also
      reduced the activation of ATR/Chk1 in gemcitabine-treated cells. Combination of
      several inhibitors revealed that Wee1 inhibition requires Cyclin-dependent
      kinases 1 and 2 (Cdk1/2) and Polo-like kinase 1 (Plk1) to reduce ATR/Chk1
      activity. Through activation of Cdks and Plk1, Wee1 inhibition reduces Claspin
      and CtIP levels, explaining the impairment in ATR/Chk1 activity. Taken together,
      these results confer a consistent signaling pathway reaching from Wee1 inhibition
      to impaired Chk1 activity, mechanistically dissecting how Wee1 inhibitors not
      only dysregulate cell cycle progression, but also enhance replicative stress and
      chemosensitivity towards nucleoside analogues. 

PMID- 25965829
TI  - Ca2+/calmodulin-dependent protein kinase IIgamma enhances stem-like traits and
      tumorigenicity of lung cancer cells.
AB  - Highly tumorigenic stem-like cells, considered tumor-initiating cells (TICs), are
      the main cause of lung cancer initiation, relapse, and drug resistance. In this
      study, we identified that Ca2+/calmodulin-dependent protein kinase IIgamma
      (CaMKIIgamma) was aberrantly expressed in highly tumorigenic stem-like lung
      cancer cells, and was also correlated with poor prognosis in human lung cancer.
      Functionally, CaMKIIgamma enhanced stem-like traits and the tumorigenicity of
      lung cancer cells in an Akt- and beta-catenin-dependent manner. In addition, we
      found that CaMKIIgamma upregulated Oct4 expression via Akt-mediated histone
      acetylation. Taken together, our findings reveal a critical role of CaMKIIgamma
      in regulating the stemness and tumorigenicity of lung cancer cells and offer a
      promising therapeutic target for TICs.

PMID- 25965830
TI  - Orosomucoid 2 inhibits tumor metastasis and is upregulated by CCAAT/enhancer
      binding protein beta in hepatocellular carcinomas.
AB  - Cancer metastasis is a complex process, and the incidence of metastasis is
      influenced by many biological factors. Orosomucoid 2 (ORM2) is an important
      glycoprotein that is mainly biosynthesized and secreted by hepatocytes. As an
      acute-phase protein, ORM2 likely plays important roles in anti-inflammation,
      immunomodulation and drug delivery. However, little is known regarding the
      function of ORM2 in hepatocellular carcinoma (HCC). In this study, we determined
      that ORM2 expression in HCC tissues was negatively associated with intrahepatic
      metastasis and histological grade. Moreover, the ectopic overexpression of ORM2
      decreased HCC cell migration and invasion in vitro and intrahepatic metastasis in
      vivo, whereas silencing ORM2 expression resulted in increased tumor cell
      migration and invasion in vitro. The CCAAT/enhancer binding protein beta
      (C/EBPbeta) upregulated ORM2 expression, while only the LAP1/2 (C/EBPbeta
      isoforms) possessed transcription-promoting activity on the ORM2 promoter.
      Subsequently, we found that LAP1 repressed HCC cell migration and invasion via
      the induction of ORM2 expression. Consistently, the protein expression of
      C/EBPbeta was negatively associated with histological grade and positively
      correlated with ORM2 protein expression in HCC tissues. Collectively, our
      findings indicate that ORM2 is a functional downstream target of C/EBPbeta and
      functions as a tumor suppressor in HCC.

PMID- 25965831
TI  - Genetic/molecular alterations of meningiomas and the signaling pathways targeted.
AB  - Meningiomas are usually considered to be benign central nervous system tumors;
      however, they show heterogenous clinical, histolopathological and cytogenetic
      features associated with a variable outcome. In recent years important advances
      have been achieved in the identification of the genetic/molecular alterations of
      meningiomas and the signaling pathways involved. Thus, monosomy 22, which is
      often associated with mutations of the NF2 gene, has emerged as the most frequent
      alteration of meningiomas; in addition, several other genes (e.g., AKT1, KLF4,
      TRAF7, SMO) and chromosomes have been found to be recurrently altered often in
      association with more complex karyotypes and involvement of multiple signaling
      pathways. Here we review the current knowledge about the most relevant genes
      involved and the signaling pathways targeted by such alterations. In addition, we
      summarize those proposals that have been made so far for classification and
      prognostic stratification of meningiomas based on their genetic/genomic features.

PMID- 25965834
TI  - CIP2A is a candidate therapeutic target in clinically challenging prostate cancer
      cell populations.
AB  - Residual androgen receptor (AR)-signaling and presence of cancer stem-like cells
      (SCs) are the two emerging paradigms for clinically challenging castration
      resistant prostate cancer (CRPC). Therefore, identification of AR-target proteins
      that are also overexpressed in the cancer SC population would be an attractive
      therapeutic approach.Our analysis of over three hundred clinical samples and
      patient-derived prostate epithelial cultures (PPECs), revealed Cancerous
      inhibitor of protein phosphatase 2A (CIP2A) as one such target. CIP2A is
      significantly overexpressed in both hormone-naive prostate cancer (HN-PC) and
      CRPC patients . CIP2A is also overexpressed, by 3- and 30-fold, in HN-PC and CRPC
      SCs respectively. In vivo binding of the AR to the intronic region of CIP2A and
      its functionality in the AR-moderate and AR-high expressing LNCaP cell-model
      systems is also demonstrated. Further, we show that AR positively regulates CIP2A
      expression, both at the mRNA and protein level. Finally, CIP2A depletion reduced
      cell viability and colony forming efficiency of AR-independent PPECs as well as
      AR-responsive LNCaP cells, in which anchorage-independent growth is also
      impaired.These findings identify CIP2A as a common denominator for AR-signaling
      and cancer SC functionality, highlighting its potential therapeutic significance
      in the most clinically challenging prostate pathology: castration-resistant
      prostate cancer. 

PMID- 25965832
TI  - Inhibition of TRPM7 by carvacrol suppresses glioblastoma cell proliferation,
      migration and invasion.
AB  - Glioblastomas are progressive brain tumors with devastating proliferative and
      invasive characteristics. Ion channels are the second largest target class for
      drug development. In this study, we investigated the effects of the TRPM7
      inhibitor carvacrol on the viability, resistance to apoptosis, migration, and
      invasiveness of the human U87 glioblastoma cell line.The expression levels of
      TRPM7 mRNA and protein in U87 cells were detected by RT-PCR, western blotting and
      immunofluorescence. TRPM7 currents were recorded using whole-cell patch-clamp
      techniques. An MTT assay was used to assess cell viability and proliferation.
      Wound healing and transwell experiments were used to evaluate cell migration and
      invasion. Protein levels of p-Akt/t-Akt, p-ERK1/2/t-ERK1/2, cleaved caspase-3,
      MMP-2 and phosphorylated cofilin were also detected.TRPM7 mRNA and protein
      expression in U87 cells is higher than in normal human astrocytes. Whole-cell
      patch-clamp recording showed that carvacrol blocks recombinant TRPM7 current in
      HEK293 cells and endogenous TRPM7-like current in U87 cells. Carvacrol treatment
      reduced the viability, migration and invasion of U87 cells. Carvacrol also
      decreased MMP-2 protein expression and promoted the phosphorylation of cofilin.
      Furthermore, carvacrol inhibited the Ras/MEK/MAPK and PI3K/Akt signaling
      pathways.Therefore, carvacrol may have therapeutic potential for the treatment of
      glioblastomas through its inhibition of TRPM7 channels.

PMID- 25965837
TI  - Catalytic Ortho-Acetoxylation of Masked Benzyl Alcohols via an Exo-Directing
      Mode.
AB  - A Pd-catalyzed ortho-acetoxylation of masked benzyl alcohols to synthesize
      various 2-hydroxyalkylphenol derivatives is reported. The 2,6-dimethoxyl
      benzaldoxime proved to be an efficient exo-type directing group for arene (sp(2))
      C-H functionalization. Two strategies were demonstrated to remove the directing
      group through N-O and C-O bond cleavages. A high catalyst turnover (>1000) was
      obtained to illustrate the practicality of this method. 

PMID- 25965833
TI  - Stromal androgen receptor regulates the composition of the microenvironment to
      influence prostate cancer outcome.
AB  - Androgen receptor (AR) signaling in stromal cells is important in prostate
      cancer, yet the mechanisms underpinning stromal AR contribution to disease
      development and progression remain unclear. Using patient-matched benign and
      malignant prostate samples, we show a significant association between low AR
      levels in cancer associated stroma and increased prostate cancer-related death at
      one, three and five years post-diganosis, and in tissue recombination models with
      primary prostate cancer cells that low stromal AR decreases castration-induced
      apoptosis. AR-regulation was found to be different in primary human fibroblasts
      isolated from adjacent to cancerous and non-cancerous prostate epithelia, and to
      represent altered activation of myofibroblast pathways involved in cell cycle,
      adhesion, migration, and the extracellular matrix (ECM). Without AR signaling,
      the fibroblast-derived ECM loses the capacity to promote attachment of both
      myofibroblasts and cancer cells, is less able to prevent cell-matrix disruption,
      and is less likely to impede cancer cell invasion. AR signaling in prostate
      cancer stroma appears therefore to alter patient outcome by maintaining an ECM
      microenvironment inhibitory to cancer cell invasion. This paper provides
      comprehensive insight into AR signaling in the non-epithelial prostate
      microenvironment, and a resource from which the prognostic and therapeutic
      implications of stromal AR levels can be further explored.

PMID- 25965835
TI  - Age-related changes in monocytes exacerbate neointimal hyperplasia after vascular
      injury.
AB  - Neointimal hyperplasia is the leading cause of restenosis after endovascular
      interventions. It is characterized by the accumulation of myofibroblast-like
      cells and extracellular matrix in the innermost layer of the wall and is
      exacerbated by inflammation. Monocytes from either young or aged rats were
      applied perivascularly to injured vascular walls of young recipient animals.
      Monocytes from aged rats, but not young donors, increased neointima thickness.
      Accordingly, the gene expression profiles of CD11b+ monocytes from aged rats
      showed significant up-regulation of genes involved in cellular adhesion, lipid
      degradation, cytotoxicity, differentiation, and inflammation. These included
      cadherin 13 (Cdh13), colony stimulating factor 1 (Csf1), chemokine C-X-C motif
      ligand 1 (Cxcl1), endothelial cell-selective adhesion molecule (Esam), and
      interferon gamma (Ifng). In conclusion, our results suggest that the increased
      inflammatory and adhesive profile of monocytes contributes to pathological wall
      remodeling in aged-related vascular diseases. 

PMID- 25965836
TI  - MicroRNA-212 suppresses tumor growth of human hepatocellular carcinoma by
      targeting FOXA1.
AB  - MicroRNA-212 (miR-212) has been reported to play oncogenic or tumor suppressive
      role in different human malignancies. Here, we demonstrated that the mean level
      of miR-212 in hepatocellular carcinoma (HCC) tissues was significantly lower than
      that in matched tumor-adjacent tissues. Similarly, the expression of miR-212 was
      obviously reduced in HCC cell lines as compared with a nontransformed hepatic
      cell line. Ectopic expression of miR-212 inhibited cell viability and
      proliferation, and induced apoptosis in HepG2 cells. In contrast, down-regulation
      of miR-212 increased cell viability and proliferation, and suppressed apoptosis
      in Bel-7402 cells. In vivo studies showed that miR-212 inhibited tumor growth of
      HCC via suppressing proliferation and inducing apoptosis. Furthermore, we
      confirmed that Forkhead box protein A1 (FOXA1) was a direct target of miR-212,
      and it abrogated the function of miR-212 in HCC. Finally, we disclosed that the
      aberrant expression of miR-212 and FOXA1 was evidently correlated with poor
      prognostic features of HCC. MiR-212, FOXA1 and their combination were valuable
      prognostic markers for predicting survival of HCC patients. In conclusion, miR
      212 may serve as a prognostic indicator for HCC patients and exerts tumor
      suppressive role, at least in part, by inhibiting FOXA1. 

PMID- 25965838
TI  - First-trimester maternal cell microRNA is a superior pregnancy marker to
      immunological testing for predicting adverse pregnancy outcome.
AB  - Patients at risk of immune-mediated pregnancy complications have historically
      relied on the use of peripheral blood immunological assays for diagnosis and
      pregnancy monitoring. However, these tests often fail to identify many at-risk
      patients, achieving moderately predictive receiver operating characteristic (ROC)
      curve AUCs of 0.60-0.70. We previously demonstrated that a microRNA panel
      comprising 30 microRNAs successfully predicts pregnancy outcome in the first
      trimester. In our current study we constructed a smaller, more clinically useful
      seven-microRNA panel from the original panel of 30 microRNAs with equivalent
      sensitivity and specificity. To select optimal microRNAs for a smaller panel,
      quantitative RT-PCR on 30 microRNAs was first performed on 48 patients (191
      samples) with concurrent immunological testing: TNFalpha/Il-10 ratio, IFNgamma/Il
      10, CD56+16+%, NK 50:1 cytotoxicity and T regulatory cells. MicroRNAs were
      separated into clusters associated with: Th1/Th2 response; T regulatory cell
      percent; pregnancy risk; treatment response. Seven most differentially expressed
      microRNAs were selected. The seven microRNA scoring system was then applied to 39
      patient samples in the first trimester of pregnancy (19 healthy deliveries, 8
      miscarriages, 12 preeclampsia [7 late-onset and 5 early-onset]) and 20 samples in
      the preconception period (2-10 weeks before conception). Predictive value was
      assessed. ROC curves for the seven-microRNA panel achieved AUC 0.92 for
      miscarriage and 0.90 for preeclampsia (blood drawn 34.9+/-19.2 days post
      implantation). For samples measured preconception, ROC curve analysis
      demonstrated AUC 0.81 for adverse pregnancy outcome. Maternal PBMC microRNA can
      identify high-risk patients likely to benefit from immunotherapy with improved
      sensitivity and specificity compared with standard immune assays. 

PMID- 25965839
TI  - Screening of Novel Li-Air Battery Catalyst Materials by a Thin Film Combinatorial
      Materials Approach.
AB  - A combinatorial synthesis and high-throughput screening process was developed for
      the investigation of potential oxygen reduction reaction (ORR) and oxygen
      evolution reaction (OER) catalysts for use as Li-air battery cathode materials.
      Libraries of discrete ternary metal alloy compositions were deposited via thin
      film sputtering. The samples were electrochemically tested in parallel using
      cyclic voltammetry in O2-saturated KOH electrolyte. Compositions were ranked by
      ORR and OER onset potentials with respect to an internal Pt reference. Results
      from the Pt-Mn-Co, Cr-Mn-Co, Pd-Mn-Co, and Pd-Mn-Ru systems are reported. Many
      alloy compositions showed marked improvement in catalytic activity compared to
      pure Pt. Among the systems considered, Pt12Mn44Co44, Pd43Co57 and Pd36Mn28Ru36 in
      particular exhibited lower overpotentials for oxygen reactions, which occur at
      the cathode in Li-air batteries. 

PMID- 25965841
TI  - Araujo A, et al. An economic analysis of erlotinib, docetaxel, pemetrexed and
      best supportive care as second or third line treatment of non-small cell lung
      cancer Rev Port Pneumol 2008; 14(6):803-827.

PMID- 25965840
TI  - A novel multiple locus variable number of tandem repeat (VNTR) analysis (MLVA)
      method for Propionibacterium acnes.
AB  - Propionibacterium acnes plays a central role in the pathogenesis of acne and is
      responsible for severe opportunistic infections. Numerous typing schemes have
      been developed that allow the identification of phylotypes, but they are often
      insufficient to differentiate subtypes. To better understand the genetic
      diversity of this species and to perform epidemiological analyses, high
      throughput discriminant genotyping techniques are needed. Here we describe the
      development of a multiple locus variable number of tandem repeats (VNTR) analysis
      (MLVA) method. Thirteen VNTRs were identified in the genome of P. acnes and were
      used to genotype a collection of clinical isolates. In addition, publically
      available sequencing data for 102 genomes were analyzed in silico, providing an
      MLVA genotype. The clustering of MLVA data was in perfect congruence with whole
      genome based clustering. Analysis of the clustered regularly interspaced short
      palindromic repeat (CRISPR) element uncovered new spacers, a supplementary source
      of genotypic information. The present MLVA13 scheme and associated internet
      database represents a first line genotyping assay to investigate large number of
      isolates. Particular strains may then be submitted to full genome sequencing in
      order to better analyze their pathogenic potential. 

PMID- 25965842
TI  - Guapsidial A and Guadials B and C: Three New Meroterpenoids with Unusual
      Skeletons from the Leaves of Psidium guajava.
AB  - A novel sesquiterpene-based Psidium meroterpenoid, possessing an unusual coupling
      pattern, and two new monoterpene-based meroterpenoids with unprecedented
      skeletons were isolated from the leaves of Psidium guajava. Their structures and
      absolute configurations were elucidated by spectroscopic, X-ray diffraction, and
      computational methods. The plausible biosynthetic pathway of these meroterpenoids
      as well as their cytotoxicities toward HepG2 and HepG2/ADM cells were also
      discussed. 

PMID- 25965843
TI  - Editorial.

PMID- 25965844
TI  - Guidelines for the management of pulmonary hypertension patients.

PMID- 25965845
TI  - Should schools expect poor physical and mental health, social adjustment, and
      participation outcomes in students with disability?
AB  - The literature on whether students with disabilities have worse physical and
      mental health, social adjustment, and participation outcomes when compared to
      their peers without disabilities is largely inconclusive. While the majority of
      case control studies showed significantly worse outcomes for students with
      disabilities; the proportion of variance accounted for is rarely reported. The
      current study used a population cross-sectional approach to determine the
      classification ability of commonly used screening and outcome measures in
      determining the disability status. Furthermore, the study aimed to identify the
      variables, if any, that best predicted the presence of disability. Results of
      univariate discriminant function analyses suggest that across the board, the
      sensitivity of the outcome/screening tools to correctly identify students with a
      disability was 31.9% higher than the related Positive Predictive Value (PPV). The
      lower PPV and Positive Likelihood Ratio (LR+) scores suggest that the included
      measures had limited discriminant ability (17.6% to 40.3%) in accurately
      identifying students at-risk for further assessment. Results of multivariate
      analyses suggested that poor health and hyperactivity increased the odds of
      having a disability about two to three times, while poor close perceived
      friendship and academic competences predicted disability with roughly the same
      magnitude. Overall, the findings of the current study highlight the need for
      researchers and clinicians to familiarize themselves with the psychometric
      properties of measures, and be cautious in matching the function of the measures
      with their research and clinical needs. 

PMID- 25965846
TI  - Iron supplementation prevents a decline in iron stores and enhances strength
      performance in elite female volleyball players during the competitive season.
AB  - The primary aim of this study was to examine the effects of 11 weeks of iron
      supplementation on hematological and strength markers in elite female volleyball
      players. Twenty-two volleyball players (aged 27.0 +/- 5.6 years) from 2 Spanish
      First National League teams participated and were counterbalanced into 1 of 2
      groups based upon iron status: (i) control group (CG, n = 11); or (ii) iron
      treatment group (ITG, n = 11), which received 325 mg/day of ferrous sulphate
      daily. Subjects performed their team's regimen of training or match play every
      day. Both groups were tested for hematological and strength levels at 2 points:
      (i) baseline (T0, before preseason) and (ii) 11 weeks later (T11, post-testing).
      Hematological parameters were serum iron (sFe), serum ferritin (FER), transferrin
      saturation index (TSI), and hemoglobin (Hb); strength assessments were bench
      press, military press, half-squat, power clean, clean and jerk, and pull-over. CG
      experienced a significant decrease (p < 0.05) for sFe (T0, 112.7 +/- 31.5; T11,
      69.0 +/- 20.5 MUg.dL(-1); -33.9%), FER (T0, 60.2 +/- 28.6; T11, 38.2 +/- 16.4
      ng.mL(-1); -34.6%), TSI (T0, 29.4% +/- 9.5%; T11, 17.4% +/- 5.1%; -35.3%), and Hb
      (T0, 14.1 +/- 1.0; T11, 13.0 +/- 0.8 g.L(-1); -7.44%); however, ITG experienced
      no changes (p > 0.05). Consequently, in ITG all hematological parameters were
      significantly greater (p < 0.05) than CG at T11. There was greater (p < 0.05)
      percent increase in the clean and jerk (CG: +5.1% +/- 20.9 vs. ITG: +29.0% +/-
      21.3%), power clean (CG: -5.8% +/- 30.3% vs. ITG: +44.6% +/- 56.6%), and total
      mean strength (CG: +10.9% +/- 3.2% vs. ITG: +26.2% +/- 3.6%) in ITG. Our findings
      suggest that oral iron supplementation prevents iron loss and enhances strength
      in female volleyball players during the competitive season. 

PMID- 25965848
TI  - Friction forces on atoms after acceleration.
AB  - The aim of this paper is to revisit the calculation of atom-surface quantum
      friction in the quantum field theory formulation put forward by Barton (2010 New
      J. Phys. 12 113045). We show that the power dissipated into field excitations and
      the associated friction force depend on how the atom is boosted from being
      initially at rest to a configuration in which it is moving at constant velocity
      (v) parallel to the planar interface. In addition, we point out that there is a
      subtle cancellation between the one-photon and part of the two-photon dissipating
      power, resulting in a leading order contribution to the frictional power which
      goes as v(4). These results are also confirmed by an alternative calculation of
      the average radiation force, which scales as v(3). 

PMID- 25965847
TI  - Upper extremity 3-dimensional reachable workspace assessment in amyotrophic
      lateral sclerosis by Kinect sensor.
AB  - INTRODUCTION: Reachable workspace is a measure that provides clinically
      meaningful information regarding arm function. In this study, a Kinect sensor was
      used to determine the spectrum of 3-dimensional reachable workspace encountered
      in a cross-sectional cohort of individuals with amyotrophic lateral sclerosis
      (ALS). METHODS: Bilateral 3D reachable workspace was recorded from 10 subjects
      with ALS and 17 healthy controls. The data were normalized by each individual's
      arm length to obtain a reachable workspace relative surface area (RSA).
      Concurrent validity was assessed by correlation with scoring on the ALS
      Functional Rating Score-revised (ALSFRSr). RESULTS: The Kinect-measured reachable
      workspace RSA differed significantly between the ALS and control subjects (0.579
      +/- 0.226 vs. 0.786 +/- 0.069; P < 0.001). The RSA demonstrated correlation with
      ALSFRSr upper extremity items (Spearman correlation rho = 0.569; P = 0.009). With
      worsening upper extremity function, as categorized by the ALSFRSr, the reachable
      workspace also decreased progressively. CONCLUSIONS: This study demonstrates the
      feasibility and potential of using a novel Kinect-based reachable workspace
      outcome measure in ALS.

PMID- 25965849
TI  - The vibration discomfort of standing people: evaluation of multi-axis vibration.
AB  - Few studies have investigated discomfort caused by multi-axis vibration and none
      has explored methods of predicting the discomfort of standing people from
      simultaneous fore-and-aft, lateral and vertical vibration of a floor. Using the
      method of magnitude estimation, 16 subjects estimated their discomfort caused by
      dual-axis and tri-axial motions (octave-bands centred on either 1 or 4 Hz with
      various magnitudes in the fore-and-aft, lateral and vertical directions) and the
      discomfort caused by single-axis motions. The method of predicting discomfort
      assumed in current standards (square-root of the sums of squares of the three
      components weighted according to their individual contributions to discomfort)
      provided reasonable predictions of the discomfort caused by multi-axis vibration.
      Improved predictions can be obtained for specific stimuli, but no single simple
      method will provide accurate predictions for all stimuli because the rate of
      growth of discomfort with increasing magnitude of vibration depends on the
      frequency and direction of vibration. 

PMID- 25965850
TI  - Comparing competitive fitness of West Nile virus strains in avian and mosquito
      hosts.
AB  - Enzootic transmission of West Nile virus (WNV; Flaviviridae, Flavivirus) involves
      various species of birds and ornithophilic mosquitoes. Single nucleotide
      substitutions in the WNV genome may impact viral fitness necessary for WNV
      adaptation and evolution as previously shown for the WN02 genotype. In an effort
      to study phenotypic change, we developed an in vivo fitness competition model in
      two biologically relevant hosts for WNV. The House Finch (HOFI; Haemorhous
      mexicanus) and Culex tarsalis mosquitoes represent moderately susceptible hosts
      for WNV, are highly abundant in Western North America and frequently are infected
      with WNV in nature. Herein, we inoculated HOFIs and Cx. tarsalis competitively
      (dually) and singly with infectious-clone derived viruses of the founding
      California isolate COAV997-2003 (COAV997-IC), the founding North American isolate
      NY99 (NY99-IC), and a 2004 field isolate from California (CA-04), and compared
      the replicative capacities (fitness) of these viruses to a genetically marked
      virus of COAV997 (COAV997-5nt) by measuring RNA copy numbers. COAV997 and COAV997
      5nt exhibited neutral fitness in HOFIs and Cx. tarsalis, and the temperature
      sensitive phenotype of COAV997 did not affect replication in HOFIs as none of the
      infected birds became febrile. The NY99 and CA-04 isolates demonstrated elevated
      fitness in HOFIs compared to COAV997-5nt, whereas all viruses replicated to
      similar titers and RNA copies in Cx. tarsalis, and the only fitness differences
      were related to infection rates. Our data demonstrated that competitive
      replication allows for the sensitive comparison of fitness differences among two
      genetically closely related viruses using relevant hosts of WNV while eliminating
      host-to-host differences. In conclusion, our approach may be helpful in
      understanding the extent of phenotypic change in fitness associated with genetic
      changes in WNV. 

PMID- 25965851
TI  - Skin rejuvenation with non-invasive pulsed electric fields.
AB  - Degenerative skin diseases affect one third of individuals over the age of sixty.
      Current therapies use various physical and chemical methods to rejuvenate skin;
      but since the therapies affect many tissue components including cells and
      extracellular matrix, they may also induce significant side effects, such as
      scarring. Here we report on a new, non-invasive, non-thermal technique to
      rejuvenate skin with pulsed electric fields. The fields destroy cells while
      simultaneously completely preserving the extracellular matrix architecture and
      releasing multiple growth factors locally that induce new cells and tissue
      growth. We have identified the specific pulsed electric field parameters in rats
      that lead to prominent proliferation of the epidermis, formation of
      microvasculature, and secretion of new collagen at treated areas without
      scarring. Our results suggest that pulsed electric fields can improve skin
      function and thus can potentially serve as a novel non-invasive skin therapy for
      multiple degenerative skin diseases. 

PMID- 25965852
TI  - Highly Active Hydrogen Evolution Electrodes via Co-Deposition of Platinum and
      Polyoxometalates.
AB  - A highly active hydrogen evolution reaction (HER) electrode with low Pt loading
      on glassy carbon (GC) has been prepared by anodic platinum dissolution and co
      deposition of polyoxometalates. TEM, EDS, XPS, CV, and ICP-MS analyses gave a Pt
      loading of 50-100 ng/cm2, corresponding to a Pt coverage of only 0.08-0.16
      monolayer. With an overpotential of 65 mV at 20 mA/cm2, the modified GC has a HER
      activity comparable to that of the commercial Pt working electrode.

PMID- 25965854
TI  - The Maillard reaction of a shrimp by-product protein hydrolysate: chemical
      changes and inhibiting effects of reactive oxygen species in human HepG2 cells.
AB  - Recently, much attention has been given to improving the antioxidant activity of
      protein hydrolysates via the Maillard reaction, but little is known about the
      cellular antioxidant activity of Maillard reaction products (MRPs) from protein
      hydrolysates. We first investigated chemical characterization and the cellular
      antioxidant activity of MRPs in a shrimp (Litopenaeus vannamei) by-product
      protein hydrolysate (SBH)-glucose system at 110  degrees C for up to 10 h of
      heating. Solutions of SBH and glucose were also heated alone as controls. The
      Maillard reaction greatly resulted in the increase of hydroxymethylfurfural (HMF)
      and browning intensity, high molecular weight fraction, and reduction of the
      total amino acid in SBH with the heating time, which correlated well with the
      free radical scavenging activity of MRPs. MRPs had stronger inhibiting effects on
      oxidative stress of human HepG2 cells than the original SBH, and its cellular
      antioxidant activity strongly correlated with free radical scavenging activity,
      but less affected by the browning intensity and HMF level. The caramelization of
      glucose partially affected the HMF level and free radical scavenging activity of
      MRPs, but it was not related to the cellular antioxidant activity. The cellular
      antioxidant activity of MRPs for 5 h of heating time appeared to reach a maximum
      level, which was mainly due to carbonyl ammonia condensation reaction. In
      conclusion, the Maillard reaction is a potential method to increase the cellular
      antioxidant activity of a shrimp by-product protein hydrolysate, but the higher
      HMF levels and the lower amino acid content in MRPs should also be considered.

PMID- 25965853
TI  - Widespread seasonal gene expression reveals annual differences in human immunity
      and physiology.
AB  - Seasonal variations are rarely considered a contributing component to human
      tissue function or health, although many diseases and physiological process
      display annual periodicities. Here we find more than 4,000 protein-coding mRNAs
      in white blood cells and adipose tissue to have seasonal expression profiles,
      with inverted patterns observed between Europe and Oceania. We also find the
      cellular composition of blood to vary by season, and these changes, which differ
      between the United Kingdom and The Gambia, could explain the gene expression
      periodicity. With regards to tissue function, the immune system has a profound
      pro-inflammatory transcriptomic profile during European winter, with increased
      levels of soluble IL-6 receptor and C-reactive protein, risk biomarkers for
      cardiovascular, psychiatric and autoimmune diseases that have peak incidences in
      winter. Circannual rhythms thus require further exploration as contributors to
      various aspects of human physiology and disease. 

PMID- 25965855
TI  - A Helical Polyphenylacetylene Having Amino Alcohol Moieties Without Chiral Side
      Groups as a Chiral Ligand for the Asymmetric Addition of Diethylzinc to
      Benzaldehyde.
AB  - One-handed helical polyphenylacetylenes having achiral amino alcohol moieties,
      but no chiral side groups, were synthesized by the helix-sense-selective
      copolymerization of an achiral phenylacetylene having an amino alcohol side group
      with a phenylacetylene having two hydroxyl groups. Since the resulting helical
      copolymers were successfully utilized as chiral ligands for the enantioselective
      alkylation of benzaldehyde with diethylzinc, we can conclude that the main-chain
      chirality based on the one-handed helical conformation is useful for the chiral
      catalysis of an asymmetric reaction for the first time. The enantioselectivities
      of the reaction were controlled by the optical purities of the helical polymer
      ligands. In addition, the polymer ligands could be easily recovered by
      precipitation after the reaction.

PMID- 25965856
TI  - An assessment of the effectiveness of high definition cameras as remote
      monitoring tools for dolphin ecology studies.
AB  - Research involving marine mammals often requires costly field programs. This
      paper assessed whether the benefits of using cameras outweighs the implications
      of having personnel performing marine mammal detection in the field. The efficacy
      of video and still cameras to detect Indo-Pacific bottlenose dolphins (Tursiops
      aduncus) in the Fremantle Harbour (Western Australia) was evaluated, with
      consideration on how environmental conditions affect detectability. The cameras
      were set on a tower in the Fremantle Port channel and videos were perused at 1.75
      times the normal speed. Images from the cameras were used to estimate position of
      dolphins at the water's surface. Dolphin detections ranged from 5.6 m to 463.3 m
      for the video camera, and from 10.8 m to 347.8 m for the still camera. Detection
      range showed to be satisfactory when compared to distances at which dolphins
      would be detected by field observers. The relative effect of environmental
      conditions on detectability was considered by fitting a Generalised Estimation
      Equations (GEEs) model with Beaufort, level of glare and their interactions as
      predictors and a temporal auto-correlation structure. The best fit model
      indicated level of glare had an effect, with more intense periods of glare
      corresponding to lower occurrences of observed dolphins. However this effect was
      not large (-0.264) and the parameter estimate was associated with a large
      standard error (0.113). The limited field of view was the main restraint in that
      cameras can be only applied to detections of animals observed rather than counts
      of individuals. However, the use of cameras was effective for long term
      monitoring of occurrence of dolphins, outweighing the costs and reducing the
      health and safety risks to field personal. This study showed that cameras could
      be effectively implemented onshore for research such as studying changes in
      habitat use in response to development and construction activities. 

PMID- 25965857
TI  - Measuring advection and diffusion of colloids in shear flow.
AB  - An analysis of the dynamics of colloids in shear flow can be challenging because
      of the superposition of diffusion and advection. We present a method that
      separates the two motions, starting from the time-dependent particle coordinates.
      The restriction of the tracking to flow lanes and the subtraction of estimated
      advective displacements are combined in an iterative scheme that eventually makes
      the spatial segmentation redundant. Tracking errors due to the neglect of lateral
      diffusion are avoided, while drifts parallel and perpendicular to the flow are
      eliminated. After explaining the principles of our method, we validate it against
      both computer simulations and experiments. A critical overall test is provided by
      the mean square displacement function at high Peclet numbers (up to 50). We
      demonstrate via simulations how the measurement accuracy depends on diffusion
      coefficients and flow rates, expressed in units of camera pixels and frames.
      Also, sample-specific issues are addressed: inaccuracies in the velocity profile
      for dilute suspensions (volume fraction <=0.03) and tracking errors for
      concentrated ones (VF >= 0.3). An analysis of experiments with colloidal spheres
      flowing through microchannels corroborates these findings and indicates
      perspectives for studies on transport, mixing, or rheology in microfluidic
      environments. 

PMID- 25965858
TI  - Strain Hardening and Size Effect in Five-fold Twinned Ag Nanowires.
AB  - Metallic nanowires usually exhibit ultrahigh strength but low tensile ductility
      owing to their limited strain hardening capability. Here we study the unique
      strain hardening behavior of the five-fold twinned Ag nanowires by nanomechanical
      testing and atomistic modeling. In situ tensile tests within a scanning electron
      microscope revealed strong strain hardening behavior of the five-fold twinned Ag
      nanowires. Molecular dynamics simulations showed that such strain hardening was
      critically controlled by twin boundaries and pre-existing defects. Strain
      hardening was size dependent; thinner nanowires achieved more hardening and
      higher ductility. The size-dependent strain hardening was found to be caused by
      the obstruction of surface-nucleated dislocations by twin boundaries. Our work
      provides mechanistic insights into enhancing the tensile ductility of metallic
      nanostructures by engineering the internal interfaces and defects. 

PMID- 25965859
TI  - Instagram #instasad?: exploring associations among instagram use, depressive
      symptoms, negative social comparison, and strangers followed.
AB  - As the use and influence of social networking continues to grow, researchers have
      begun to explore its consequences for psychological well-being. Some research
      suggests that Facebook use can have negative consequences for well-being.
      Instagram, a photo-sharing social network created in 2010, has particular
      characteristics that may make users susceptible to negative consequences. This
      study tested a theoretically grounded moderated meditation model of the
      association between Instagram use and depressive symptoms through the mechanism
      of negative social comparison, and moderation by amount of strangers one follows.
      One hundred and seventeen 18-29 year olds completed online questionnaires
      containing demographics, frequency of Instagram use, amount of strangers followed
      on Instagram, the Center for Epidemiological Resources Scale for Depression, and
      the Social Comparison Rating Scale. Instagram use was marginally positively
      associated with depressive symptoms, and positive social comparison was
      significantly negatively associated with depressive symptoms. Amount of strangers
      followed moderated the associations of Instagram use with social comparison
      (significantly) and depressive symptoms (marginally), and further significantly
      moderated the indirect association of Instagram use with depressive symptoms
      through social comparison. Findings generally suggest that more frequent
      Instagram use has negative associations for people who follow more strangers, but
      positive associations for people who follow fewer strangers, with social
      comparison and depressive symptoms. Implications of negative associations of
      social networking for people who follow strangers and the need for more research
      on Instagram use given its increasing popularity are explored. 

PMID- 25965860
TI  - The mainstreaming of verbally aggressive online political behaviors.
AB  - The purpose of this paper was to investigate the relationship between verbal
      aggression and uncivil media attention on political flaming. More specifically,
      this paper examines whether the use of uncivil media programming is associated
      with the perceived acceptability and intention to engage in aggressive online
      discussions (i.e., online political flaming) and whether this relationship varies
      by verbal aggression. The results show that individuals less inclined to engage
      in aggressive communication tactics (i.e., low in verbal aggression) become more
      accepting of flaming and show greater intention to flame as their attention to
      uncivil media increases. By contrast, those with comparatively higher levels of
      verbal aggression show a decrease in acceptance and intention to flame as their
      attention to these same media increases. 

PMID- 25965861
TI  - Parental influences on adolescent video game play: a study of accessibility,
      rules, limit setting, monitoring, and cybersafety.
AB  - Adolescents' video gaming is increasing at a rapid rate. Yet, little is known
      about what factors contribute toward more hours of gaming per week, as well as
      what factors may limit or protect adolescents from excessive gaming. The aim of
      the present study was to examine associations between adolescents' accessibility
      to video gaming devices, the locations played (i.e., bedroom, shared rooms),
      parental regulation of technology use, and the amount of hours spent video gaming
      during the week (weekdays vs. weekends). Adolescents (N=422; age 16.3+/-2.0
      years, 41% male) completed an online questionnaire battery, including
      demographics, video gaming behaviors (e.g., hours played weekdays/weekends, time
      of day played, devices owned, locations played, etc.), and a questionnaire
      measuring aspects of parents' regulation of game playing (e.g., rules, limit
      setting, co-gaming). Accessibility to the adolescents' own devices, but not
      shared devices or device portability, was predictive of hours gaming on weekdays
      and weekends. Location (i.e., bedroom) was associated with increased gaming
      across the week. Parents discussing cybersafety was predictive of lower hours of
      gaming (weekdays and weekends). However, limit setting, monitoring, and co-gaming
      showed no significant effects. Adolescents' access to their own gaming equipped
      devices, as well as gaming in their bedrooms, were linked to increased hours of
      gaming. The findings suggest that in order to curb the increase in hours gaming,
      parents are advised to delay the ownership of adolescents' devices, encourage use
      in shared rooms, and discuss aspects of cybersafety with their teenage children. 

PMID- 25965862
TI  - Encounters in an online brand community: development and validation of a metric
      for value co-creation by customers.
AB  - Recent developments in service marketing have demonstrated the potential value co
      creation by customers who participate in online brand communities (OBCs).
      Therefore, this study forecasts the co-created value by understanding the
      participation/behavior of customers in a multi-stakeholder OBC. This six-phase
      qualitative and quantitative investigation conceptualizes, constructs, refines,
      and tests a 12-item three-dimensional scale for measuring key factors that are
      related to the experience, interpersonal interactions, and social relationships
      that affect the value co-creation by customers in an OBC. The scale captures
      stable psychometric properties, measured using various reliability and validity
      tests, and can be applied across various industries. Finally, the utility
      implications and limitations of the proposed scale are discussed, and potential
      future research directions considered. 

PMID- 25965863
TI  - Mind navigators of chemicals' experimenters? A web-based description of e
      psychonauts.
AB  - Within online drug fora communities, there are some "educated and informed" users
      who can somehow provide reliable information on psychoactive compounds and
      combinations. These users, also called "e-psychonauts," may possess levels of
      technical knowledge relating to a range of novel psychoactive substances (NPS).
      The present project aimed at identifying and describing the e-psychonauts' socio
      demographic characteristics and their motivations and patterns of drug intake. A
      netnographic research methodology, carried out through an unobtrusive
      observational approach of a list of cyber drug communities (blogs, fora,
      Facebook, and Twitter pages) was carried out. The fora posts and threads were
      accurately reviewed, analyzed, and compared using the empirical phenomenological
      psychological (EPP) method. Data were collected between January and February
      2014. Psychonauts typically considered themselves as "psychedelic researchers,"
      "new Shamans," "philosophers," or "alchemists." They appeared to be mainly young,
      males, unmarried, and Caucasians. They presented with good or excellent
      employment conditions and with a set of key skills, including attention to their
      inner "soul"; high standards of knowledge about drugs' chemical and
      pharmacological issues; and high levels of both IT skills and verbal fluency in
      reporting their own "on drug" experiences. The e-psychonauts seemed to "test" and
      at times synthesize a range of drugs to achieve the state of consciousness they
      find most pleasurable. There is the need to improve both the existing levels of
      professionals' knowledge on this novel generation of drug misusers and to design
      and develop novel prevention approaches that are able to attract the attention of
      the e-psychonauts. 

PMID- 25965864
TI  - Do It Yourself: Examination of Self-Injury First Aid Tips on YouTube.
AB  - Individuals who engage in nonsuicidal self-injury (NSSI) may prefer the Internet
      as a medium to communicate about NSSI experiences and obtain NSSI information.
      Recent research suggests that NSSI first aid information is shared. Yet, no
      research has examined the context in which this information occurs. This study
      examined the nature and scope of NSSI first aid tips on YouTube using a content
      analysis to examine 40 NSSI first aid videos. Findings indicated that videos were
      viewed 157,571 total times; they were typically favorably viewed. Most had a
      neutral purpose and neither encouraged nor discouraged NSSI. Messages encouraging
      NSSI help seeking were scant. Similarly, medical help seeking was not commonly
      encouraged, with several videos providing "safe" NSSI instructions. Overall,
      videos with NSSI first aid information may contribute to NSSI reinforcement and
      the belief that professional and medical help may not be needed for NSSI.
      Findings have implications for research, clinical work, and e-outreach, which are
      discussed. 

PMID- 25965868
TI  - Peritoneal Dialysis in Acute Kidney Injury: Trends in the Outcome across Time
      Periods.
AB  - Peritoneal dialysis (PD) should be considered a suitable method of renal
      replacement therapy in acute kidney injury (AKI) patients. This study is the
      largest cohort providing patient characteristics, clinical practice, patterns and
      their relationship to outcomes in a developing country. Its objective was to
      describe the main determinants of patient and technique survival, including
      trends over time of PD treatment in AKI patients. This was a Brazilian
      prospective cohort study in which all adult AKI patients on PD were studied from
      January/2004 to January/2014. For comparison purposes, patients were divided into
      2 groups according to the year of treatment: 2004-2008 and 2009-2014. Patient
      survival and technique failure (TF) were analyzed using the competing risk model
      of Fine and Gray. A total of 301 patients were included, 51 were transferred to
      hemodialysis (16.9%) during the study period. The main cause of TF was mechanical
      complication (47%) followed by peritonitis (41.2%). There was change in TF during
      the study period: compared to 2004-2008, patients treated at 2009-2014 had
      relative risk (RR) reduction of 0.86 (95% CI 0.77-0.96) and three independent
      risk factors were identified: period of treatment at 2009 and 2014, sepsis and
      age> 65 years. There were 180 deaths (59.8%) during the study. Death was the
      leading cause of dropout (77.9% of all cases) mainly by sepsis (58.3%), followed
      cardiovascular disease (36.1%). The overall patient survival was 41% at 30 days.
      Patient survival improved along study periods: compared to 2004-2008, patients
      treated at 2009-2014 had a RR reduction of 0.87 (95% CI 0.79-0.98). The
      independent risk factors for mortality were sepsis, age >70 years, ATN-ISS > 0.65
      and positive fluid balance. As conclusion, we observed an improvement in patient
      survival and TF along the years even after correction for several confounders and
      using a competing risk approach.

PMID- 25965867
TI  - In vivo and in vitro evidence that intrinsic upper- and lower-limb skeletal
      muscle function is unaffected by ageing and disuse in oldest-old humans.
AB  - AIM: To parse out the impact of advanced ageing and disuse on skeletal muscle
      function, we utilized both in vivo and in vitro techniques to comprehensively
      assess upper- and lower-limb muscle contractile properties in 8 young (YG; 25 +/-
      6 years) and 8 oldest-old mobile (OM; 87 +/- 5 years) and 8 immobile (OI; 88 +/-
      4 years) women. METHODS: In vivo, maximal voluntary contraction (MVC),
      electrically evoked resting twitch force (RT), and physiological cross-sectional
      area (PCSA) of the quadriceps and elbow flexors were assessed. Muscle biopsies of
      the vastus lateralis and biceps brachii facilitated the in vitro assessment of
      single fibre-specific tension (Po). RESULTS: In vivo, compared to the young, both
      the OM and OI exhibited a more pronounced loss of MVC in the lower limb [OM (
      60%) and OI (-75%)] than the upper limb (OM = -51%; OI = -47%). Taking into
      account the reduction in muscle PCSA (OM = -10%; OI = -18%), only evident in the
      lower limb, by calculating voluntary muscle-specific force, the lower limb of the
      OI (-40%) was more compromised than the OM (-13%). However, in vivo, RT in both
      upper and lower limbs (approx. 9.8 N m cm(-2) ) and Po (approx. 123 mN mm(-2) ),
      assessed in vitro, implies preserved intrinsic contractile function in all
      muscles of the oldest-old and were well correlated (r = 0.81). CONCLUSION: These
      findings suggest that in the oldest-old, neither advanced ageing nor disuse, per
      se, impacts intrinsic skeletal muscle function, as assessed in vitro. However, in
      vivo, muscle function is attenuated by age and exacerbated by disuse, implicating
      factors other than skeletal muscle, such as neuromuscular control, in this
      diminution of function.

PMID- 25965870
TI  - Determination of low-level radiostrontium, with emphasis on in situ pre
      concentration of Sr from large volume of freshwater sample using Powdex resin.
AB  - An improved analytical method was developed for determining of low levels of
      radiostrontium in environmental freshwater samples. Emphasis was placed to the in
      situ pre-concentration of radiostrontium with Powdex resin in large volumes (100
      300 L) of freshwater samples from many locations without using of deleterious
      substances such as NaOH and mineral acids. Measuring electric conductivity (EC)
      of water samples enabled the estimation of the amount of Powdex resin required
      for quantitative recovery of Sr from the large water samples in the field. The
      Powdex resin that adsorbed Sr was brought back to the laboratory, and Sr adsorbed
      in the resin was eluted by 8 M HNO3 together with Sr carrier added. Strontium was
      radiochemically separated by the cation exchange method for beta counting after
      removal of most of the Ca using Ca(OH)2 precipitation. Through the procedure the
      Sr chemical yield was 88% on average. This analytical method was verified by
      analyzing 170 L of water samples with different salinity values, to which a known
      amount of (90)Sr was added. The detection limits of (90)Sr activities obtained
      using the 170 L water samples was estimated to be approximately 0.1 mBq L(-1) for
      a counting time of 100 min. The method was also applied to environmental samples
      collected from Ibaraki and Fukushima prefectures; their (90)Sr activities ranged
      from 0.16 to 0.93 mBq L(-)(1). 

PMID- 25965869
TI  - Novel autosomal dominant mutation in loricrin presenting as prominent ichthyosis.

PMID- 25965871
TI  - Extending the recovery window: Effects of trait rumination on subsequent evening
      cortisol following a laboratory performance stressor.
AB  - Mental rehearsal of past stressors through rumination may extend the
      physiological stress response and exposure to stress-related physiological
      mediators, such as cortisol. If repeated over time, this prolonged activation may
      contribute to a number of chronic health conditions. Findings from the emerging
      literature on the tendency to ruminate and its association with cortisol have
      been somewhat mixed. In the present study, we tested whether trait rumination
      predicted elevated cortisol concentrations in response to a performance stressor,
      and whether this association varied by the social-evaluative context of the
      stressor and gender. We also examined whether associations persisted into the
      evening of the stressor. Participants (50% female; mean age=19.83, SD=1.62) were
      randomly assigned to complete a laboratory speech stressor either in a social
      evaluative (SET; n=86) or non-evaluative context (non-SET; n=58). Salivary
      cortisol concentrations were measured throughout the laboratory visit and later
      that evening. There was a main effect of trait rumination on greater total
      cortisol exposure into the evening of the stressor. In addition, trait rumination
      interacted with stressor context to predict cortisol declines: on the night of
      the SET stressor, high trait ruminators did not exhibit typical declines in
      cortisol. Different cortisol patterns emerged for men and women with tendencies
      to ruminate: women with higher rumination scores had flatter cortisol slopes with
      greater evening cortisol, whereas men with higher trait rumination scores had
      greater initial cortisol reactivity to the stressor. Together, these findings
      suggest that the relationship between the tendency to ruminate and cortisol
      concentrations is qualified by individual differences (gender) and stressor
      characteristics (social-evaluative threat). 

PMID- 25965872
TI  - n-3 PUFAs have beneficial effects on anxiety and cognition in female rats:
      Effects of early life stress.
AB  - Stressful life events, especially those in early life, can exert long-lasting
      changes in the brain, increasing vulnerability to mental illness especially in
      females. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) play a critical role in
      the development and function of the central nervous system (CNS). Thus, we
      investigated the influence of an eicosapentaenoic acid (EPA)/docosahexaenoic acid
      (DHA) (80% EPA, 20% DHA) n-3 PUFAs mixture on stress-related behavioural and
      neurobiological responses. Sprague-Dawley female rats were subjected to an early
      life stress, maternal separation (MS) procedure from postnatal days 2 to 12. Non
      separated (NS) and MS rats were administered saline, EPA/DHA 0.4g/kg/day or
      EPA/DHA 1g/kg/day, respectively. In adulthood, EPA/DHA treated animals had a dose
      dependent reduction in anxiety in NS rats. Furthermore, cognitive performance in
      the novel object recognition task (NOR) was improved by EPA/DHA treatment in NS
      animals only. EPA/DHA 1g/kg/day decreased behavioural despair in the forced swim
      test. Notably, EPA/DHA high dose increased the translocation of GRs into the
      nucleus of NS rat hippocampus. However, the levels of mBDNF remained unchanged in
      all the experimental groups. The corticosterone response to an acute stress was
      blunted in MS rats and this was further attenuated by pre-treatment with EPA/DHA.
      Immune response and monoamine neurotransmission were significantly altered by
      early-life stress. In conclusion, our study supports the view that n-3 PUFAs are
      beneficial in neurodevelopmentally normal animals but have little positive
      benefit in animals exposed to early life stress. 

PMID- 25965873
TI  - Divergent strategy for the synthesis of original dihydrobenzo- and dihydronaphtho
      acridines.
AB  - A straightforward access to numerous novel substituted dihydrobenzo- and
      dihydronaphthoacridines is described using a unique molecular platform in two key
      steps. A large range of carbon-based substituents such as aromatic, vinyl,
      alkynyl fragments through Pd-catalysed couplings has been installed. The
      molecular diversity is extended to the introduction of aza-heterocycles and
      further authorizes the installation of alkylamino chains by means of Cu-promoted
      C-N bond formation. Possible access to quinolinium salts is also described. The
      methodology revealed convenient preparation of a wide panel of molecules that
      display various rigidity/flexibility and lipophilic/hydrophilic balances.
      Finally, the influence of structural modulations on the photophysical properties
      of these novel architectures is also studied. It is noteworthy that styryl and
      alkynyl derivatives are emissive in water (phiF up to 12%). 

PMID- 25965874
TI  - A method for quantification of volatile organic compounds in blood by SPME-GC
      MS/MS with broader application: From non-occupational exposure population to
      exposure studies.
AB  - Humans are continuously exposed to volatile organic compounds (VOCs) as these
      chemicals are ubiquitously present in most indoor and outdoor environments. In
      order to assess recent exposure to VOCs for population-based studies, VOCs are
      measured in the blood of participants. This work describes an improved method to
      detect 12 VOCs by head-space solid-phase microextraction gas chromatography
      coupled with isotope-dilution mass spectrometry in selected reaction monitoring
      mode (SPME-GC-MS/MS). This method was applied to the analysis of trihalomethanes,
      styrene, trichloroethylene, tetrachloroethylene and BTEX (benzene, toluene,
      ethylbenzene, m-xylene, p-xylene, o-xylene) in a population-based biomonitoring
      study (Canadian Health Measures Survey). The method showed good linearity
      (>0.990) in the range of 0.010-10MUg/L and detection limits between 0.007 and
      0.027MUg/L, precision better than 25% and good accuracy (+/-25%) based on
      proficiency testing materials. Quality Control data among runs over a 7 month
      period showed %RSD between 14 and 25% at low levels (~0.03MUg/L) and between 9
      and 23% at high levels (~0.4MUg/L). The method was modified to analyze samples
      from a pharmacokinetic study in which 5 healthy volunteers were exposed to
      single, binary and quaternary mixtures of CTEX (chloroform, ethylbenzene, toluene
      and m-xylene), thus the expected concentration in blood was 1 order of magnitude
      higher than those found in the general population. The method was modified by
      reducing the sample size (from 3g to 0.5g) and increasing the upper limit of the
      concentration range to 395MUg/L. Good linearity was found in the range of 0.13
      395MUg/L for toluene and ethylbenzene and 0.20-609MUg/L for m/p-xylene. Quality
      control data among runs over the period of the study (n=13) were found to vary
      between 7 and 25%. 

PMID- 25965875
TI  - Simultaneous determination of acetaminophen and dihydrocodeine in human plasma by
      UPLC-MS/MS: Its pharmacokinetic application.
AB  - An ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS)
      method was developed and validated to determine acetaminophen (AAP) and
      dihydrocodeine (DHC) in human plasma simultaneously. Plasma samples were prepared
      using protein precipitation with acetonitrile, the two analytes and the internal
      standard midazolam were separated on an Acquity UPLC BEH C18 column and mass
      spectrometric analysis was performed using a QTrap5500 mass spectrometer coupled
      with an electro-spray ionization (ESI) source in the positive ion mode. The MRM
      transitions of m/z 151.2->110.0 and m/z 302.3->199.2 were used to quantify for
      AAP and DHC, respectively. The linearity of this method was found to be within
      the concentration range of 50-10000ng/mL for AAP, and 1-100ng/mL for DHC in human
      plasma, respectively. The lower limit of quantification (LLOQ) was 50ng/mL and
      1ng/mL for AAP and DHC in human plasma, respectively. The relative standard
      deviations (RSD) of intra and inter precision were less than 10% for both AAP and
      DHC. The analysis time of per sample was 1.0min. The developed and validated
      method was successfully applied to a pharmacokinetic study of AAP (500mg) with
      DHC (20mg) capsule in Chinese healthy volunteers (N=20). 

PMID- 25965876
TI  - Simultaneous determination of polycyclic musks in blood and urine by solid
      supported liquid-liquid extraction and gas chromatography-tandem mass
      spectrometry.
AB  - A rapid, precise and accurate method for the simultaneous determination of 5
      polycyclic musks (PCMs) in biological fluids was developed by solid supported
      liquid-liquid extraction (SLE) coupled with gas chromatography-tandem mass
      spectrometry (GC-MS/MS). All parameters influencing SLE-GC-MS performance,
      including electron energy of electron-impact ionization source, collision energy
      for tandem mass spectrometer when operated in selected-reaction monitoring (SRM)
      mode, type and volume of elution reagent, nitrogen evaporation time, pH and
      salinity of sample have been carefully optimized. Eight milliliter of n-hexane
      was finally chosen as elution reagent. Blood and urine sample could be loaded
      into SLE cartridge without adjusting pH and salinity. Deuterated tonalide (AHTN
      d3) was chosen as internal standard. The correlation coefficient (r(2)) of the
      calibration curves of target compounds ranged from 0.9996 to 0.9998. The dynamic
      range spanned over two orders of magnitude. The limit of detection (LOD) of
      target compounds in blood and urine ranged from 0.008 to 0.105MUgL(-1) and 0.005
      to 0.075MUgL(-1), respectively. The developed procedure was successfully applied
      to the analysis of PCMs in human blood and urine obtaining satisfying recoveries
      on low, medium and high levels. The method was compared with SLE-GC-MS and shown
      one to two orders of magnitude improvement in sensitivity. 

PMID- 25965878
TI  - Low-Frequency Raman Fingerprints of Two-Dimensional Metal Dichalcogenide Layer
      Stacking Configurations.
AB  - The tunable optoelectronic properties of stacked two-dimensional (2D) crystal
      monolayers are determined by their stacking orientation, order, and atomic
      registry. Atomic-resolution Z-contrast scanning transmission electron microscopy
      (AR-Z-STEM) and electron energy loss spectroscopy (EELS) can be used to determine
      the exact atomic registration between different layers, in few-layer 2D stacks;
      however, fast optical characterization techniques are essential for rapid
      development of the field. Here, using two- and three-layer MoSe2 and WSe2
      crystals synthesized by chemical vapor deposition, we show that the generally
      unexplored low frequency (LF) Raman modes (<50 cm(-1)) that originate from
      interlayer vibrations can serve as fingerprints to characterize not only the
      number of layers, but also their stacking configurations. Ab initio calculations
      and group theory analysis corroborate the experimental assignments determined by
      AR-Z-STEM and show that the calculated LF mode fingerprints are related to the 2D
      crystal symmetries. 

PMID- 25965879
TI  - Diet-related risk factors for leprosy: a case-control study.
AB  - BACKGROUND: Food shortage was associated with leprosy in two recent studies
      investigating the relation between socioeconomic factors and leprosy. Inadequate
      intake of nutrients due to food shortage may affect the immune system and
      influence the progression of infection to clinical leprosy. We aimed to identify
      possible differences in dietary intake between recently diagnosed leprosy
      patients and control subjects. METHODS: In a leprosy endemic area of Bangladesh,
      newly diagnosed leprosy patients and control subjects were interviewed about
      their socioeconomic situation, health and diet. Dietary intakes were recorded
      with a 24-hour recall, from which a Dietary Diversity Score (DDS) was calculated.
      Body Mass Index (BMI) was calculated and Household Food Insecurity Access Scale
      (HFIAS) was filled out for every participant. Using logistic regression, a
      univariate, block wise multivariate, and an integrated analysis were carried out.
      RESULTS: 52 leprosy cases and 100 control subjects were included. Food shortage
      was more common, dietary diversity was lower and household food insecurity was
      higher in the patient group. Patients consumed significantly less items from the
      DDS food groups 'Meat and fish' and 'Other fruits and vegetables.' Lower food
      expenditure per capita, lower BMI, lower DDS and absence of household food stocks
      are the main factors associated with an increased risk of having leprosy.
      CONCLUSION: Low income families have only little money to spend on food and
      consequently have a low intake of highly nutritious non-rice foods such as meat,
      fish, milk, eggs, fruits and vegetables. Development of clinical leprosy could be
      explained by deficiencies of the nutrients that these foods normally provide.

PMID- 25965881
TI  - Casimir friction: relative motion more generally.
AB  - This paper extends our recent study on Casimir friction forces for dielectric
      plates moving parallel to each other (Hoye and Brevik 2014 Eur. Phys. J. D 68
      61), to a case where the plates are no longer restricted to rectilinear motion.
      Part of the mathematical formalism thereby becomes more cumbersome, but reduces
      in the end to the form that we expected to be the natural one in advance. As an
      example, we calculate the Casimir torque on a planar disc rotating with constant
      angular velocity around its vertical symmetry axis next to another plate. 

PMID- 25965880
TI  - CBL controls a tyrosine kinase network involving AXL, SYK and LYN in nilotinib
      resistant chronic myeloid leukaemia.
AB  - A tyrosine kinase network composed of the TAM receptor AXL and the cytoplasmic
      kinases LYN and SYK is involved in nilotinib-resistance of chronic myeloid
      leukaemia (CML) cells. Here, we show that the E3-ubiquitin ligase CBL down
      regulation occurring during prolonged drug treatment plays a critical role in
      this process. Depletion of CBL in K562 cells increases AXL and LYN protein
      levels, promoting cell resistance to nilotinib. Conversely, forced expression of
      CBL in nilotinib-resistant K562 cells (K562-rn) dramatically reduces AXL and LYN
      expression and resensitizes K562-rn cells to nilotinib. A similar mechanism was
      found to operate in primary CML CD34(+) cells. Mechanistically, the E3-ligase CBL
      counteracts AXL/SYK signalling, promoting LYN transcription by controlling AXL
      protein stability. Surprisingly, the role of AXL in resistance was independent of
      its ligand GAS6 binding and its TK activity, in accordance with a scaffold
      activity for this receptor being involved in this cellular process. Collectively,
      our results demonstrate a pivotal role for CBL in the control of a tyrosine
      kinase network mediating resistance to nilotinib treatment in CML cells.

PMID- 25965882
TI  - Reversible near-infrared/blue mechanofluorochromism of aminobenzopyranoxanthene.
AB  - Mechanochromic organic molecules (MOMs) that exhibit a large difference of
      fluorescence wavelength between two states have important potential applications,
      but few such compounds are known. Here, we report a new MOM, cis-ABPX01(0), which
      shows switchable near-IR and blue fluorescence responses. Detailed
      spectrophotometric and single-crystal X-ray analyses revealed that the near-IR
      fluorescence is attributable to fluorescence from slip-stacked dimeric structures
      in crystals, while the blue fluorescence is attributable to fluorescence from the
      monomer. Switching between the two is achieved by dynamic structural
      interconversion between the two molecular packing arrangements in response to
      mechanical grinding and solvent vapor-fuming. 

PMID- 25965883
TI  - Full-scale validation of an air scour control system for energy savings in
      membrane bioreactors.
AB  - Membrane aeration represents between 35 and 50% of the operational cost of
      membrane bioreactors (MBR). New automatic control systems and/or module
      configurations have been developed for aeration optimization. In this paper, we
      briefly describe an innovative MBR air scour control system based on permeability
      evolution and present the results of a full-scale validation that lasted over a 1
      year period. An average reduction in the air scour flow rate of 13% was achieved,
      limiting the maximum reduction to 20%. This averaged reduction corresponded to a
      decrease in energy consumption for membrane aeration of 14% (0.025 kWh m(-3))
      with maximum saving rates of 22% (0.04 kWh m(-3)). Permeability and fouling rate
      evolution were not affected by the air scour control system, as very similar
      behavior was observed for these variables for both filtration lines throughout
      the entire experimental evaluation period of 1 year. 

PMID- 25965884
TI  - Pre-treatments, characteristics, and biogeochemical dynamics of dissolved organic
      matter in sediments: A review.
AB  - Dissolved organic matter (DOM) in sediments, termed here sediment DOM, plays a
      variety of important roles in global biogeochemical cycling of carbon and
      nutrients as well as in the fate and transport of xenobiotics. Here we reviewed
      sediment DOM, including pore waters and water extractable organic matter from
      inland and coastal sediments, based on recent literature (from 1996 to 2014).
      Sampling, pre-treatment, and characterization methods for sediment DOM were
      summarized. The characteristics of sediment DOM have been compared along an
      inland to coastal ecosystems gradient and also with the overlying DOM in water
      column to distinguish the unique nature of it. Dissolved organic carbon (DOC)
      from inland sediment DOM was generally higher than coastal areas, while no
      notable differences were found for their aromaticity and apparent molecular
      weight. Fluorescence index (FI) revealed that mixed sources are dominant for
      inland sediment DOM, but marine end-member prevails for coastal sediment DOM.
      Many reports showed that sediments operate as a net source of DOC and
      chromophoric DOM (CDOM) to the water column. Sediment DOM has shown more
      enrichment of nitrogen- and sulfur-containing compounds in the elemental
      signature than the overlying DOM. Fluorescent fingerprint investigated by
      excitation-emission matrix coupled with parallel factor analysis (EEM-PARAFAC)
      further demonstrated the characteristics of sediment DOM lacking in the photo
      oxidized and the intermediate components, which are typically present in the
      overlying surface water. In addition, the biogeochemical changes in sediment DOM
      and the subsequent environmental implications were discussed with the focus on
      the binding and the complexation properties with pollutants. 

PMID- 25965885
TI  - Global and local health burden trade-off through the hybridisation of
      quantitative microbial risk assessment and life cycle assessment to aid water
      management.
AB  - Life cycle assessment (LCA) and quantitative risk assessment (QRA) are commonly
      used to evaluate potential human health impacts associated with proposed or
      existing infrastructure and products. Each approach has a distinct objective and,
      consequently, their conclusions may be inconsistent or contradictory. It is
      proposed that the integration of elements of QRA and LCA may provide a more
      holistic approach to health impact assessment. Here we examine the possibility of
      merging LCA assessed human health impacts with quantitative microbial risk
      assessment (QMRA) for waterborne pathogen impacts, expressed with the common
      health metric, disability adjusted life years (DALYs). The example of a recent
      large-scale water recycling project in Sydney, Australia was used to identify and
      demonstrate the potential advantages and current limitations of this approach. A
      comparative analysis of two scenarios - with and without the development of this
      project - was undertaken for this purpose. LCA and QMRA were carried out
      independently for the two scenarios to compare human health impacts, as measured
      by DALYs lost per year. LCA results suggested that construction of the project
      would lead to an increased number of DALYs lost per year, while estimated disease
      burden resulting from microbial exposures indicated that it would result in the
      loss of fewer DALYs per year than the alternative scenario. By merging the
      results of the LCA and QMRA, we demonstrate the advantages in providing a more
      comprehensive assessment of human disease burden for the two scenarios, in
      particular, the importance of considering the results of both LCA and QRA in a
      comparative assessment of decision alternatives to avoid problem shifting. The
      application of DALYs as a common measure between the two approaches was found to
      be useful for this purpose. 

PMID- 25965886
TI  - Evaluation of FRNA coliphages as indicators of human enteric viruses in a
      tropical urban freshwater catchment.
AB  - This study aimed to evaluate the relationship between FRNA coliphages (FRNA GI to
      GIV) and human enteric viruses (human adenoviruses, HAdV, astroviruses, AstV,
      noroviruses, NoV, and rotaviruses, RoV) in a tropical urban freshwater catchment.
      Positive associations between human-specific coliphages and human viral pathogens
      substantiate their use as viral indicators and in microbial source tracking.
      Reverse transcription qPCR was used to measure the concentrations of viruses and
      FRNA coliphages in concentrated water samples. Environmental water samples were
      also analyzed for male-specific (F+) and somatic (Som) coliphages using plaque
      assay. The most abundant enteric virus was NoV (55%) followed by HAdV (33%), RoV
      (33%), and AstV (23%), while the most abundant FRNA genogroup was GI (85%)
      followed by GII (48%), GIV (8%) and GIII (7%). Concentrations of human-specific
      coliphages FRNA GII were positively correlated with NoV, HAdV, RoV, AstV, F+ and
      Som (tau = 0.5 to 0.3, P < 0.05) while concentrations of animal-specific
      coliphages FRNA GI were negatively correlated with HAdV and RoV (tau = -0.2, P <
      0.05). This study demonstrates statistical relationships between human-specific
      coliphages and a suite of human enteric viruses in the environment. 

PMID- 25965887
TI  - Reactivity of beta-blockers/agonists with aqueous permanganate. Kinetics and
      transformation products of salbutamol.
AB  - The possible oxidation of two beta-blockers, atenolol and propranolol, and one
      beta-agonist, salbutamol, with aqueous potassium permanganate (KMnO4) was
      investigated by liquid chromatography-quadrupole-time-of-flight-mass spectrometry
      (LC-QTOF-MS). Under strong oxidation conditions (2 mg L(-1) KMnO4, 24 h), only
      salbutamol did significantly react. In this way, the oxidation kinetics of
      salbutamol was further investigated at different concentrations of KMnO4,
      chloride, phosphate and sample pH by means of a full factorial experimental
      design. Depending on these factors, half-lives were in the range 1-144 min for
      drug and it was observed that KMnO4 concentration was the most significant
      factor, resulting in increased reaction rate as it is increased. Moreover, the
      reaction of salbutamol is also enhanced at basic pH and to a minor extent by the
      presence of phosphates, being both factors more relevant at low KMnO4
      concentrations. The use of an accurate-mass LC-QTOF-MS system permitted the
      identification of a total of seven transformation products (TPs). The
      transformation path of the drug begins by the attack of KMnO4 on two double bonds
      of the aromatic ring of salbutamol via 3 + 2 and 2 + 2 addition reactions, which
      resulted in the ring opening and that continues with oxidative reactions to
      finally produce smaller size TPs, ending with tert-butyl-formamide, as the
      smallest TP identified. Reaction in real samples showed a slower and partial
      oxidation of the pharmaceutical, due to other competing water organic
      constituents, but still exceeding 60%. Moreover, the software predicted toxicity
      of TPs indicates that they are expected not to be more toxic than salbutamol, in
      contrast to the results obtained for the predicted toxicity of chlorination TPs,
      excepting predicted developmental toxicity. 

PMID- 25965888
TI  - Adsorption of halogenated aliphatic contaminants by graphene nanomaterials.
AB  - In this study, adsorption of ten environmentally halogenated aliphatic synthetic
      organic compounds (SOCs) by a pristine graphene nanosheet (GNS) and a reduced
      graphene oxide (rGO) was examined, and their adsorption behaviors were compared
      with those of a single-walled carbon nanotube (SWCNT) and a granular activated
      carbon (GAC). In addition, the impacts of background water components (i.e.,
      natural organic matter (NOM), ionic strength (IS) and pH) on the SOC adsorption
      behavior were investigated. The results indicated HD3000 and SWCNT with higher
      microporous volumes exhibited higher adsorption capacities for the selected
      aliphatic SOCs than graphenes, demonstrating microporosity of carbonaceous
      adsorbents played an important role in the adsorption. Analysis of adsorption
      isotherms demonstrated that hydrophobic interactions were the dominant
      contributor to the adsorption of aliphatic SOCs by graphenes. However, pi-pi
      electron donor-acceptor and van der Waals interactions are likely the additional
      mechanisms contributing to the adsorption of aliphatic SOCs on graphenes. Among
      the three background solution components examined, NOM showed the most
      influential effect on adsorption of the selected aliphatic SOCs, while pH and
      ionic strength had a negligible effects. The NOM competition on aliphatic
      adsorption was less pronounced on graphenes than SWCNT. Overall, in terms of
      adsorption capacities, graphenes tested in this study did not exhibit a major
      advantage over SWCNT and GAC for the adsorption of aliphatic SOCs. 

PMID- 25965889
TI  - Chlorination and chloramination of bisphenol A, bisphenol F, and bisphenol A
      diglycidyl ether in drinking water.
AB  - Bisphenol A (BPA), bisphenol F (BPF), and bisphenol A diglycidyl ether (BADGE)
      are common components of epoxy coatings used in food packaging and in drinking
      water distribution systems. Thus, leachates from the epoxy may be exposed to the
      disinfectants free chlorine (Cl2/HOCl/OCl(-)) and monochloramine (MCA, NH2Cl).
      Bisphenols are known endocrine disrupting chemicals (EDC) with estrogenic
      activity. Chlorination by-products have the potential to have reduced or enhanced
      estrogenic qualities, and are, therefore, of interest. In this work, chlorination
      reactions for bisphenols and BADGE were explored (via LC/MS/MS) and kinetic
      modeling (using a pseudo-first order approach) was conducted to predict the fate
      of these compounds in drinking water. The half-lives of BPA and BPF with 1 mg/L
      of free chlorine ranged from 3 to 35 min over the pH range from 6 to 11 and the
      temperature range of 10-25  degrees C. Half-lives for reactions of BPA and BPF
      with a nominal MCA concentration of 3.5 mg/L as Cl2 were from 1 to 10 days and
      were greater at higher pH and lower temperature. Formation of chlorinated
      bisphenol A by-products was observed during the kinetic studies. BADGE was found
      unreactive with either oxidant. 

PMID- 25965890
TI  - Longitudinal association of neighborhood variables with Body Mass Index in Dutch
      school-age children: The KOALA Birth Cohort Study.
AB  - Changes in the neighborhood environment may explain part of the rapid increase in
      childhood overweight and obesity during the last decades. To date few theory
      driven rather than data-driven studies have explored longitudinal associations
      between multiple neighborhood characteristics and child body weight development.
      We aimed to assess the relationship between physical, social and perceived safety
      related characteristics of the neighborhood and Body Mass Index (BMI) development
      in children during early school age, using a longitudinal design. We included an
      examination of moderating and confounding factors based on a conceptual model
      adapted from the EnRG framework (Environmental Research framework for weight Gain
      prevention) and empirical research. Analyses included 1887 children from the
      KOALA Birth Cohort Study followed from baseline age 4-5 years until 8-9 years.
      For children age 4-5 years, parents completed a questionnaire measuring
      characteristics of the neighborhood. Reliability and factor analyses were used to
      identify constructs for neighborhood characteristics. Linear regression analysis
      was performed to assess the relationship between neighborhood constructs and BMI
      z-scores cross-sectionally at age 4-5 years and longitudinally using Generalized
      Estimating Equations with BMI z-scores over 5 repeated measurements until age 8-9
      years. Fourteen constructs were identified and grouped in three domains including
      perceived physical, social, or safety related characteristics of the
      neighborhood. Cross-sectionally, a lower BMI z-score was associated with higher
      perceived physical attractiveness of the neighborhood environment (standardized
      regression coefficient (beta) -0.078, 95% CI -0.123 to -0.034) and a higher level
      of social capital (beta -0.142, -0.264 to -0.019). Longitudinally, similar
      associations were observed with potentially even stronger regression
      coefficients. This study suggests that BMI in children is mainly related to the
      modifiable physical and social environment of the conceptual model and not
      related to safety as perceived by parents. 

PMID- 25965891
TI  - Rationalising prescribing: Evidence, marketing and practice-relevant knowledge.
AB  - Initiatives in the name of 'rational pharmacotherapy' have been launched to alter
      what is seen as 'inappropriate' prescribing practices of physicians. Based on
      observations and interviews with 20 general practitioners (GPs) in 2009-2011, we
      explored how attempts to rationalise prescribing interact with chronic care
      management in Denmark. We demonstrate how attempts to rationalise prescribing by
      informing GPs about drug effects, adverse effects and price do not satisfy GPs'
      knowledge needs. We argue that, for GPs, 'rational' prescribing cannot be
      understood in separation from the processes that enable patients to use
      medication. Therefore, GPs do much more to obtain knowledge about medications
      than seek advice on 'rational pharmacotherapy'. For instance, GPs also seek
      opportunities to acquaint themselves with the material objects of medication and
      medical devices. We conceptualise the knowledge needs of GPs as a need for
      practice-relevant knowledge and argue that industry sales representatives are
      granted opportunity to access general practice because they understand this need
      of GPs. 

PMID- 25965892
TI  - Who benefits from removing user fees for facility-based delivery services?
      Evidence on socioeconomic differences from Ghana, Senegal and Sierra Leone.
AB  - Coverage of skilled delivery care has been increasing across most low-income
      countries; however, it remains far from universal and is very unequally
      distributed according to socioeconomic position. In an effort to increase
      coverage of skilled delivery care and reduce socioeconomic inequalities,
      governments of several countries in sub-Saharan Africa have recently adopted
      policies that remove user fees for facility-based delivery services. There is
      little rigorous evidence of the impact of these policies and few studies have
      examined effects on socioeconomic inequalities. This study investigates the
      impact of recent delivery fee exemption policies in Ghana, Senegal, and Sierra
      Leone on socioeconomic differences in the use of facility-based delivery
      services. Using Demographic and Health Survey data from nine sub-Saharan African
      countries, we evaluated the user fee policy changes using a difference-in
      differences approach that accounts for underlying common secular trends and time
      invariant differences among countries, and allows for differential effects of the
      policy by socioeconomic position. Removing user fees was consistent with
      meaningful increases in facility deliveries across all categories of household
      wealth and maternal education. We found little evidence of differential effects
      of removing user fees across quartiles of household wealth, with increases of 5.4
      facility deliveries per hundred live births (95% CI: 2.1, 8.8) among women in the
      poorest quartile and 6.8 per hundred live births (95% CI: 4.0, 9.7) for women in
      the richest quartile. However, our results suggest that educated women benefited
      more from removing user fees compared to women with no education. For women with
      at least some secondary education, the estimated effect was 8.6 facility
      deliveries per hundred live births (95% CI: 5.4, 11.9), but only 4.6 per hundred
      live births (95% CI: 2.2, 7.0) for women with no education (heterogeneity p-value
      = 0.04). Thus, while removing fees at the point of service increased facility
      deliveries across the socioeconomic gradient, it did not reduce inequalities
      defined by household wealth and may have contributed to a widening of educational
      inequalities. These findings emphasize the need for concerted efforts to address
      financial and other barriers that contribute to large and persistent
      socioeconomic inequalities in delivery care. 

PMID- 25965893
TI  - Water systems, sanitation, and public health risks in remote communities: Inuit
      resident perspectives from the Canadian Arctic.
AB  - Safe drinking water and wastewater sanitation are universally recognized as
      critical components of public health. It is well documented that a lack of access
      to these basic services results in millions of preventable deaths each year among
      vulnerable populations. Water and wastewater technologies and management
      practices are frequently tailored to local environmental conditions. Also
      important, but often overlooked in water management planning, are the social,
      cultural and economic contexts in which services are provided. The purpose of
      this qualitative case study was to identify and understand residents' perceptions
      of the functionality of current water and wastewater sanitation systems in one
      vulnerable context, that of a remote Arctic Aboriginal community (Coral Harbour,
      Nunavut), and to identify potential future water related health risks. Semi
      structured interviews were conducted with 28 Inuit residents and 9 key informants
      in 2011 and 2012. Findings indicate that the population's rapid transition from a
      semi-nomadic hunting and gathering lifestyle to permanent settlements with
      municipally provided utilities is influencing present-day water usage patterns,
      public health perceptions, and the level of priority decision-makers place on
      water and wastewater management issues. Simultaneously environmental, social and
      cultural conditions conducive to increased human exposure to waterborne health
      risks were also found to exist and may be increasing in the settlements. While
      water and wastewater system design decisions are often based on best practices
      proven suitable in similar environmental conditions, this study reinforces the
      argument for inclusion of social, cultural, and economic variables in such
      decisions, particularly in remote and economically challenged contexts in Canada
      or elsewhere around the world. The results also indicate that the addition of
      qualitative data about water and wastewater systems users' behaviours to
      technical knowledge of systems and operations can enhance the understanding of
      human-water interactions and be valuable in risk assessments and intervention
      development. 

PMID- 25965894
TI  - Moderators, mediators, and bidirectional relationships in the International
      Classification of Functioning, Disability and Health (ICF) framework: An
      empirical investigation using a longitudinal design and Structural Equation
      Modeling (SEM).
AB  - The International Classification of Functioning, Disability and Health (ICF)
      published in 2001 describes the consequences of health conditions with three
      components of impairments in body structures or functions, activity limitations
      and participation restrictions. Two of the new features of the conceptual model
      were the possibility of feedback effects between each ICF component and the
      introduction of contextual factors conceptualized as moderators of the
      relationship between the components. The aim of this longitudinal study is to
      provide empirical evidence of these two kinds of effect. Structural equation
      modeling was used to analyze data from a French population-based cohort of 548
      patients with knee osteoarthritis recruited between April 2007 and March 2009 and
      followed for three years. Indicators of the body structure and function, activity
      and participation components of the ICF were derived from self-administered
      standardized instruments. The measurement model revealed four separate factors
      for body structures impairments, body functions impairments, activity limitations
      and participation restrictions. The classic sequence from body impairments to
      participation restrictions through activity limitations was found at each
      assessment time. Longitudinal study of the ICF component relationships showed a
      feedback pathway indicating that the level of participation restrictions at
      baseline was predictive of activity limitations three years later. Finally, the
      moderating role of personal (age, sex, mental health, etc.) and environmental
      factors (family relationships, mobility device use, etc.) was investigated. Three
      contextual factors (sex, family relationships and walking stick use) were found
      to be moderators for the relationship between the body impairments and the
      activity limitations components. Mental health was found to be a mediating factor
      of the effect of activity limitations on participation restrictions. 

PMID- 25965895
TI  - Tracing shadows: How gendered power relations shape the impacts of maternal death
      on living children in sub Saharan Africa.
AB  - Driven by the need to better understand the full and intergenerational toll of
      maternal mortality (MM), a mixed-methods study was conducted in four countries in
      sub-Saharan Africa to investigate the impacts of maternal death on families and
      children. The present analysis identifies gender as a fundamental driver not only
      of maternal, but also child health, through manifestations of gender inequity in
      household decision making, labor and caregiving, and social norms dictating the
      status of women. Focus group discussions were conducted with community members,
      and in depth qualitative interviews with key-informants and stakeholders, in
      Tanzania, Ethiopia, Malawi, and South Africa between April 2012 and October 2013.
      Findings highlight that socially constructed gender roles, which define mothers
      as caregivers and fathers as wage earners, and which limit women's agency
      regarding childcare decisions, among other things, create considerable gaps when
      it comes to meeting child nutrition, education, and health care needs following a
      maternal death. Additionally, our findings show that maternal deaths have
      differential effects on boy and girl children, and exacerbate specific risks for
      girl children, including early marriage, early pregnancy, and school drop-out. To
      combat both MM, and to mitigate impacts on children, investment in health
      services interventions should be complemented by broader interventions regarding
      social protection, as well as aimed at shifting social norms and opportunity
      structures regarding gendered divisions of labor and power at household,
      community, and society levels. 

PMID- 25965896
TI  - Benzo(a)pyrene Metabolism and EROD and GST Biotransformation Activity in the
      Liver of Red- and White-Blooded Antarctic Fish.
AB  - Climate change and anthropogenic pollution are of increasing concern in remote
      areas such as Antarctica. The evolutionary adaptation of Antarctic notothenioid
      fish to the cold and stable Southern Ocean led to a low plasticity of their
      physiological functions, what may limit their capacity to deal with altered
      temperature regimes and pollution in the Antarctic environment. Using a
      biochemical approach, we aimed to assess the hepatic biotransformation capacities
      of Antarctic fish species by determining (i) the activities of ethoxyresorufin-O
      deethylase (EROD) and glutathione-S-transferase (GST), and (ii) the metabolic
      clearance of benzo(a)pyrene by hepatic S9 supernatants. In addition, we
      determined the thermal sensitivity of the xenobiotic biotransformation enzymes.
      We investigated the xenobiotic metabolism of the red-blooded Gobionotothen
      gibberifrons and Notothenia rossii, the hemoglobin-less Chaenocephalus aceratus
      and Champsocephalus gunnari, and the rainbow trout Oncorhynchus mykiss as a
      reference. Our results revealed similar metabolic enzyme activities and metabolic
      clearance rates between red- and white-blooded Antarctic fish, but significantly
      lower rates in comparison to rainbow trout. Therefore, bioaccumulation factors
      for metabolizable lipophilic contaminants may be higher in Antarctic than in
      temperate fish. Likewise, the thermal adaptive capacities and flexibilities of
      the EROD and GST activities in Antarctic fish were significantly lower than in
      rainbow trout. As a consequence, increasing water temperatures in the Southern
      Ocean will additionally compromise the already low detoxification capacities of
      Antarctic fish. 

PMID- 25965898
TI  - Beyond Assessment: Conducting Theoretically Grounded Research on Service-Learning
      in Gerontology Courses.
AB  - Service-learning is a useful pedagogical tool and high-impact practice, providing
      multiple benefits. Gerontology (and other) courses frequently include service
      learning activities but lack theory-based, intentional research on outcomes.
      Here, the authors define service-learning and contextualize it in higher
      education, provide an overview of research and assessment in service-learning and
      gerontology courses, demonstrate the shortcomings of program evaluations, and
      offer suggestions for future research to advance and generate theory. 

PMID- 25965897
TI  - New Monocyclic, Bicyclic, and Tricyclic Ethynylcyanodienones as Activators of the
      Keap1/Nrf2/ARE Pathway and Inhibitors of Inducible Nitric Oxide Synthase.
AB  - A monocyclic compound 3 (3-ethynyl-3-methyl-6-oxocyclohexa-1,4-dienecarbonitrile)
      is a highly reactive Michael acceptor leading to reversible adducts with
      nucleophiles, which displays equal or greater potency than the pentacyclic
      triterpenoid CDDO in inflammation and carcinogenesis related assays. Recently,
      reversible covalent drugs, which bind with protein targets but not permanently,
      have been gaining attention because of their unique features. To explore such
      reversible covalent drugs, we have synthesized monocyclic, bicyclic, and
      tricyclic compounds containing 3 as an electrophilic fragment and evaluated them
      as activators of the Keap1/Nrf2/ARE pathway and inhibitors of iNOS. Notably,
      these compounds maintain the unique features of the chemical reactivity and
      biological potency of 3. Among them, a monocyclic compound 5 is the most potent
      in these assays while a tricyclic compound 14 displays a more robust and specific
      activation profile compared to 5. In conclusion, we demonstrate that 3 is a
      useful electrophilic fragment for exploring reversible covalent drugs. 

PMID- 25965899
TI  - Spatio-temporal heterogeneity in tumor liposome uptake: Characterization of macro
      and microdistribution.

PMID- 25965900
TI  - Glioblastoma Multiforme Recurrence: An Exploratory Study of (18)F FPPRGD2 PET/CT.
AB  - PURPOSE: To prospectively evaluate fluorine 18 ((18)F) 2-fluoropropionyl-labeled
      PEGylated dimeric arginine-glycine-aspartic acid (RGD) peptide (PEG3
      E[c{RGDyk}]2) (FPPRGD2) positron emission tomography (PET) in patients with
      glioblastoma multiforme (GBM). MATERIALS AND METHODS: The institutional review
      board approved this HIPAA-compliant protocol. Written informed consent was
      obtained from each patient. (18)F FPPRGD2 uptake was measured semiquantitatively
      in the form of maximum standardized uptake values (SUV(max)) and uptake volumes
      before and after treatment with bevacizumab. Vital signs and laboratory results
      were collected before, during, and after the examinations. A nonparametric
      version of multivariate analysis of variance was used to assess safety outcome
      measures simultaneously across time points. A paired two-sample t test was
      performed to compare SUV(max). RESULTS: A total of 17 participants (eight men,
      nine women; age range, 25-65 years) were enrolled prospectively. (18)F FPPRGD2
      PET/computed tomography (CT), (18)F fluorodeoxyglucose (FDG) PET/CT, and brain
      magnetic resonance (MR) imaging were performed within 3 weeks, prior to the start
      of bevacizumab therapy. In eight of the 17 patients (47%), (18)F FPPRGD2 PET/CT
      was repeated 1 week after the start of bevacizumab therapy; six patients (35%)
      underwent (18)F FPPRGD2 PET/CT a third time 6 weeks after starting bevacizumab
      therapy. There were no changes in vital signs, electrocardiographic findings, or
      laboratory values that qualified as adverse events. One patient (6%) had
      recurrent GBM identified only on (18)F FPPRGD2 PET images, and subsequent MR
      images enabled confirmation of recurrence. Of the 17 patients, 14 (82%) had
      recurrent GBM identified on (18)F FPPRGD2 PET and brain MR images, while (18)F
      FDG PET enabled identification of recurrence in 13 (76%) patients. Two patients
      (12%) had no recurrent GBM. CONCLUSION: (18)F FPPRGD2 is a safe PET
      radiopharmaceutical that has increased uptake in GBM lesions. Larger cohorts are
      required to confirm these preliminary findings.

PMID- 25965901
TI  - Quantitative Assessment of Inflammation in a Porcine Acute Terminal Ileitis
      Model: US with a Molecularly Targeted Contrast Agent.
AB  - PURPOSE: To evaluate the feasibility and reproducibility of ultrasonography (US)
      performed with dual-selectin-targeted contrast agent microbubbles (MBs) for
      assessment of inflammation in a porcine acute terminal ileitis model, with
      histologic findings as a reference standard. MATERIALS AND METHODS: The study had
      institutional Animal Care and Use Committee approval. Acute terminal ileitis was
      established in 19 pigs; four pigs served as control pigs. The ileum was imaged
      with clinical-grade dual P- and E-selectin-targeted MBs (MBSelectin) at
      increasing doses (0.5, 1.0, 2.5, 5.0, 10, and 20 * 10(8) MB per kilogram of body
      weight) and with control nontargeted MBs (MBControl). For reproducibility
      testing, examinations were repeated twice after the MBSelectin and MBControl
      injections. After imaging, scanned ileal segments were analyzed ex vivo both for
      inflammation grade (by using hematoxylin-eosin staining) and for expression of
      selectins (by using quantitative immunofluorescence analysis). Statistical
      analysis was performed by using the t test, intraclass correlation coefficients
      (ICCs), and Spearman correlation analysis. RESULTS: Imaging signal increased
      linearly (P < .001) between a dose of 0.5 and a dose of 5.0 * 10(8) MB/kg and
      plateaued between a dose of 10 and a dose of 20 * 10(8) MB/kg. Imaging signals
      were reproducible (ICC = 0.70), and administration of MBSelectin in acute ileitis
      resulted in a significantly higher (P < .001) imaging signal compared with that
      in control ileum and MBControl. Ex vivo histologic grades of inflammation
      correlated well with in vivo US signal (rho = 0.79), and expression levels of
      both P-selectin (37.4% +/- 14.7 [standard deviation] of vessels positive; P <
      .001) and E-selectin (31.2% +/- 25.7) in vessels in the bowel wall of segments
      with ileitis were higher than in control ileum (5.1% +/- 3.7 for P-selectin and
      4.8% +/- 2.3 for E-selectin). CONCLUSION: Quantitative measurements of
      inflammation obtained by using dual-selectin-targeted US are reproducible and
      correlate well with the extent of inflammation at histologic examination in a
      porcine acute ileitis model as a next step toward clinical translation.

PMID- 25965902
TI  - Can Shear-Wave Elastography be Used to Discriminate Obstructive Hydronephrosis
      from Nonobstructive Hydronephrosis in Children?
AB  - PURPOSE: To determine if ultrasonographic (US) renal shear-wave speed (SWS)
      measurements obtained either before or after intravenous diuretic administration
      can be used to discriminate obstructive hydronephrosis from unobstructive
      hydronephrosis in children, with diuretic renal scintigraphy as the reference
      standard. MATERIALS AND METHODS: Institutional review board approval and parental
      informed consent were obtained for this HIPAA-compliant prospective cross
      sectional blind comparison with a reference standard. Between November 2012 and
      September 2014, 37 children (mean age, 4.1 years; age range, 1 month to 17 years)
      underwent shear-wave elastography of the kidneys immediately before and
      immediately after diuretic renal scintigraphy (reference standard for presence of
      urinary tract obstruction). Median SWS measurements (in meters per second), as
      well as change in median SWS (median SWS after diuretic administration minus
      median SWS before diuretic administration) were correlated with the amount of
      time required for kidney radiotracer activity to fall by 50% after intravenous
      administration of the diuretic (T1/2). Median SWS measurements were compared with
      degree of obstruction and degree of hydronephrosis with analysis of variance.
      Receiver operating characteristic (ROC) curves were created. RESULTS: Radiotracer
      T1/2 values after diuretic administration did not correlate with median SWS
      measurements obtained before (r = -0.08, P = .53) or after (r = -0.0004, P >.99)
      diuretic administration, nor did they correlate with intraindividual change in
      median SWS (r = 0.07, P = .56). There was no significant difference in pre- or
      postdiuretic median SWS measurements between kidneys with scintigraphic evidence
      of no, equivocal, or definite urinary tract obstruction (P > .5) or for median
      SWS measurements between kidneys with increasing degree of hydronephrosis (P >
      .5). ROC curves showed poor diagnostic performance of median SWS in discerning
      no, equivocal, or definite urinary tract obstruction (area under the ROC curve
      ranged from 0.50 to 0.62). CONCLUSION: US SWS measurements did not enable
      discrimination of obstructive hydronephrosis from unobstructive hydronephrosis in
      children.

PMID- 25965903
TI  - Microparticles: Bridging the Gap between Autoimmunity and Thrombosis.
AB  - Microparticles (MPs) are irregularly shaped small vesicles of heterogeneous size
      released from the plasma membrane in a tightly controlled process, after
      different stimuli. MPs have been associated with proinflammatory effects and also
      with autoimmune processes, being a source of autoantigenic nuclear material,
      which can form immune complexes. In addition, recent reports have linked a large
      number of autoimmune disorders to an increased risk of thrombosis, and MPs seem
      to promote the potential for thrombotic events. A growing mass of evidence
      supports the idea that MPs could contribute to the generation of an inflammation
      induced hypercoagulability state, having a relevant role in the pathogenesis of
      the thrombotic phenomena associated to autoimmune disease, such as systemic lupus
      erythematosus, antiphospholipid antibody syndrome, and systemic vasculitis. In
      this review, we focus on the procoagulant properties of circulating MPs and
      analyze their contribution to the pathogenesis of autoimmune diseases. 

PMID- 25965904
TI  - Dependence of Ion Dynamics on the Polymer Chain Length in Poly(ethylene oxide)
      Based Polymer Electrolytes.
AB  - It is known from experiments that in the polymer electrolyte system, which
      contains poly(ethylene oxide) chains (PEO), lithium-cations (Li(+)), and
      bis(trifluoromethanesulfonyl)imide-anions (TFSI(-)), the cation and the anion
      diffusion and the ionic conductivity exhibit a similar chain-length dependence:
      with increasing chain length, they start dropping steadily, and later, they
      saturate to constant values. These results are surprising because Li-cations are
      strongly correlated with the polymer chains, whereas TFSI-anions do not have such
      bonding. To understand this phenomenon, we perform molecular dynamics simulations
      of this system for four different polymer chain lengths. The diffusion results
      obtained from our simulations display excellent agreement with the experimental
      data. The cation transport model based on the Rouse dynamics can successfully
      quantify the Li-diffusion results, which correlates Li diffusion with the polymer
      center-of-mass motion and the polymer segmental motion. The ionic conductivity as
      a function of the chain length is then estimated based on the chain-length
      dependent ion diffusion, which shows a temperature-dependent deviation for short
      chain lengths. We argue that in the first regime, counterion correlations modify
      the conductivity, whereas for the long chains, the system behaves as a strong
      electrolyte. 

PMID- 25965905
TI  - Avoiding drying-artifacts in transmission electron microscopy: Characterizing the
      size and colloidal state of nanoparticles.
AB  - Standard transmission electron microscopy nanoparticle sample preparation
      generally requires the complete removal of the suspending liquid. Drying often
      introduces artifacts, which can obscure the state of the dispersion prior to
      drying and preclude automated image analysis typically used to obtain number
      weighted particle size distribution. Here we present a straightforward protocol
      for prevention of the onset of drying artifacts, thereby allowing the
      preservation of in-situ colloidal features of nanoparticles during TEM sample
      preparation. This is achieved by adding a suitable macromolecular agent to the
      suspension. Both research- and economically-relevant particles with high
      polydispersity and/or shape anisotropy are easily characterized following our
      approach (http://bsa.bionanomaterials.ch), which allows for rapid and
      quantitative classification in terms of dimensionality and size: features that
      are major targets of European Union recommendations and legislation. 

PMID- 25965906
TI  - A clinicopathologic study of morphea in Korean patients.
AB  - BACKGROUND: The exact pathogenesis of morphea is poorly understood, and only a
      few clinical or histopathological studies have been conducted in Asian patients.
      OBJECTIVE: The aim of this study was to identify the clinical and
      histopathological characteristics of morphea in Korean patients. METHODS: We
      retrospectively reviewed the medical records of 101 patients whose
      clinicopathologic findings were compatible with morphea and analyzed demographic
      characteristics, number of lesions, disease subtype and histopathological
      findings. RESULTS: Overall, circumscribed morphea (52.5%) was the most common
      clinical type, followed by linear (28.7%), mixed (13.9%) and generalized (5.0%)
      type. Disease duration was positively correlated with increased thickness of the
      skin in 54 patients (p < 0.001). Inflammatory cell infiltration was absent in 54,
      mild in 30 and moderate in 14 patients. There was no significant difference in
      the mean ratio of lesional to normal skin thickness (L/N ratio) among four types
      of morphea. Disease duration was not correlated with the density of inflammatory
      cell infiltration (p = 0.68). There were statistically significant differences in
      the duration of disease according to plasma cell counts (p < 0.05). CONCLUSIONS:
      A positive correlation was found between skin thickness and disease duration, but
      mean L/N ratio was not significantly different among various types of morphea.

PMID- 25965907
TI  - Nanomedicine and nanotechnology are rapidly developing fields across the nation
      and worldwide.

PMID- 25965909
TI  - Exploring the Content of Post-Traumatic Stress Symptoms among Parents after
      Paediatric Stem Cell Transplant.
AB  - In the present study the aim was to explore the content in a trauma reported in a
      self-report questionnaire by parents of children with a life threatening illness.
      Semi-structured interviews were performed, with the aim to explore the specific
      cognitive and behavioral content of the trauma related symptoms reported by the
      individual informant. The transcripts of the interviews were analyzed with
      content analysis using a direct approach with a-priori categories according to
      the B and C categories of the DSM-IV diagnostic criteria for PTSD. The results
      give us the picture of a complex situation, where the self-report instrument PCL
      captured a spectrum of qualitatively different cognitions. The parents described
      traumatic thoughts and images relating not only to experiences in the past (i.e.,
      truly post-traumatic), but also to current stressors and expected future events. 

PMID- 25965908
TI  - Association between Several Persistent Organic Pollutants and Thyroid Hormone
      Levels in Cord Blood Serum and Bloodspot of the Newborn Infants of Korea.
AB  - Current knowledge on adverse endocrine disruption effects of persistent organic
      pollutants (POPs) among newborn infants is limited and often controversial. To
      investigate the associations between prenatal exposure to major POPs and thyroid
      hormone levels among newborn infants, both cord serum or maternal serum
      concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl
      ethers (PBDEs), and organochlorine pesticides (OCPs) were compared with five
      thyroid hormones in cord serum of newborn infants as well as TSH in bloodspot
      collected at 2 day after birth (n=104). Since cord serum thyroid hormones could
      be affected by those of mothers, thyroid hormone concentrations of the matching
      mothers at delivery were adjusted. In cord serum, BDE-47, -99, and Sigmachlordane
      (CHD) showed significant positive associations with cord or bloodspot TSH. At the
      same time, p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) and hexachlorbenzene
      (HCB) showed negative associations with total T3 and total T4 in cord serum,
      respectively. Maternal exposure to beta-hexachlorhexane (beta-HCH), SigmaCHD,
      SigmaDDT, or p,p'-DDE were also associated with neonatal thyroid hormones.
      Although the sample size is small and the thyroid hormone levels of the subjects
      were within the reference range, our observation supports thyroid disrupting
      potential of several POPs among newborn infants, at the levels occurring in the
      general population. Considering the importance of thyroid hormones during
      gestation and early life stages, health implication of thyroid hormone effects by
      low level POPs exposure deserves further follow up investigations. 

PMID- 25965910
TI  - In Vitro Anti-Echinococcal and Metabolic Effects of Metformin Involve Activation
      of AMP-Activated Protein Kinase in Larval Stages of Echinococcus granulosus.
AB  - Metformin (Met) is a biguanide anti-hyperglycemic agent, which also exerts
      antiproliferative effects on cancer cells. This drug inhibits the complex I of
      the mitochondrial electron transport chain inducing a fall in the cell energy
      charge and leading 5'-AMP-activated protein kinase (AMPK) activation. AMPK is a
      highly conserved heterotrimeric complex that coordinates metabolic and growth
      pathways in order to maintain energy homeostasis and cell survival, mainly under
      nutritional stress conditions, in a Liver Kinase B1 (LKB1)-dependent manner. This
      work describes for the first time, the in vitro anti-echinococcal effect of Met
      on Echinococcus granulosus larval stages, as well as the molecular
      characterization of AMPK (Eg-AMPK) in this parasite of clinical importance. The
      drug exerted a dose-dependent effect on the viability of both larval stages.
      Based on this, we proceeded with the identification of the genes encoding for the
      different subunits of Eg-AMPK. We cloned one gene coding for the catalytic
      subunit (Eg-ampkalpha) and two genes coding for the regulatory subunits (Eg
      ampkbeta and Eg-ampkgamma), all of them constitutively transcribed in E.
      granulosus protoscoleces and metacestodes. Their deduced amino acid sequences
      show all the conserved functional domains, including key amino acids involved in
      catalytic activity and protein-protein interactions. In protoscoleces, the drug
      induced the activation of AMPK (Eg-AMPKalpha-P176), possibly as a consequence of
      cellular energy charge depletion evidenced by assays with the fluorescent
      indicator JC-1. Met also led to carbohydrate starvation, it increased
      glucogenolysis and homolactic fermentation, and decreased transcription of
      intermediary metabolism genes. By in toto immunolocalization assays, we detected
      Eg-AMPKalpha-P176 expression, both in the nucleus and the cytoplasm of cells as
      in the larval tegument, the posterior bladder and the calcareous corpuscles of
      control and Met-treated protoscoleces. Interestingly, expression of Eg-AMPKalpha
      was observed in the developmental structures during the de-differentiation
      process from protoscoleces to microcysts. Therefore, the Eg-AMPK expression
      during the asexual development of E. granulosus, as well as the in vitro synergic
      therapeutic effects observed in presence of Met plus albendazole sulfoxide
      (ABZSO), suggest the importance of carrying out chemoprophylactic and clinical
      efficacy studies combining Met with conventional anti-echinococcal agents to test
      the potential use of this drug in hydatidosis therapy. 

PMID- 25965912
TI  - Isolation of human adult olfactory sphere cells as a cell source of neural
      progenitors.
AB  - Olfactory stem cells are generated from olfactory mucosa. Various culture
      conditions generate olfactory stem cells that differ according to species and
      developmental stage and have different progenitor or stem cell characteristics.
      Olfactory spheres (OSs) are clusters of progenitor or stem cells generated from
      olfactory mucosa in suspension culture. In this study, adult human OSs were
      generated and their characteristics analyzed. Human OSs were adequately produced
      from olfactory mucosa with area over 40 mm(2). Immunocytochemistry (ICC) and
      fluorescence-activated cell sorting showed that human OSs were AN2 and A2B5
      positive. Immunofluorescence analysis of cell type-specific ICC indicated that
      the number of Tuj1-positive OS cells was significantly elevated. Tuj1-positive
      cells displayed typical neuronal soma and dendritic morphology. Human OS cells
      were also immunopositive for MAP2. By contrast, few RIP-, O4-, and GFAP-positive
      cells were present. These RIP, O4, and GFAP-positive cells did not resemble bona
      fide oligodendrocytes and astrocytes morphologically. In culture to induce
      differentiation of oligodendrocytes, human OS cells also expressed neuronal
      markers, but neither oligodendrocyte or astrocyte markers. These findings suggest
      that human OS cells autonomously differentiate into neurons in our culture
      condition and have potential to be used as a cell source of neural progenitors
      for their own regenerative grafts, avoiding the need for immunosuppression and
      ethical controversies.

PMID- 25965913
TI  - 17 Ways to Say Yes: Toward Nuanced Tone of Voice in AAC and Speech Technology.
AB  - People with complex communication needs who use speech-generating devices have
      very little expressive control over their tone of voice. Despite its importance
      in human interaction, the issue of tone of voice remains all but absent from AAC
      research and development however. In this paper, we describe three
      interdisciplinary projects, past, present and future: The critical design
      collection Six Speaking Chairs has provoked deeper discussion and inspired a
      social model of tone of voice; the speculative concept Speech Hedge illustrates
      challenges and opportunities in designing more expressive user interfaces; the
      pilot project Tonetable could enable participatory research and seed a research
      network around tone of voice. We speculate that more radical interactions might
      expand frontiers of AAC and disrupt speech technology as a whole. 

PMID- 25965911
TI  - PUMA mediates the combinational therapy of 5-FU and NVP-BEZ235 in colon cancer.
AB  - Colon cancer is the third most common cancer in humans which has a high mortality
      rate, and 5-Fluorouracil (5-FU) is one of the most widely used drugs in colon
      cancer therapy. However, acquired chemoresistance is becoming the major
      challenges for patients, and the molecular mechanism underlying the development
      of 5-FU resistance is still poorly understood. In this study, a newly designed
      therapy in combination with 5-FU and NVP-BEZ235 in colon cancer cells (HCT-116
      and RKO) was established, to investigate the mechanism of 5-FU resistance and
      optimize drug therapy to improve outcome for patients. Our results show 5-FU
      induced cell apoptosis through p53/PUMA pathway, with aberrant Akt activation,
      which may well explain the mechanism of 5-FU resistance. NVP-BEZ235 effectively
      up-regulated PUMA expression, mainly through inactivation of PI3K/Akt and
      activation of FOXO3a, leading to cell apoptosis even in the p53-/- HCT-116 cells.
      Combination treatment of 5-FU and NVP-BEZ235 further increased cell apoptosis in
      a PUMA/Bax dependent manner. Moreover, significantly enhanced anti-tumor effects
      were observed in combination treatment in vivo. Together, these results
      demonstrated that the combination treatment of 5-FU and NVP-BEZ235 caused PUMA
      dependent tumor suppression both in vitro and in vivo, which may promise a more
      effective strategy for colon cancer therapy. 

PMID- 25965914
TI  - First quantum mechanics/molecular mechanics studies of the inhibition mechanism
      of cruzain by peptidyl halomethyl ketones.
AB  - Cruzain is a primary cysteine protease expressed by the protozoan parasite
      Trypanosoma cruzi during Chagas disease infection, and thus, the development of
      inhibitors of this protein is a promising target for designing an effective
      therapy against the disease. In this paper, the mechanism of inhibition of
      cruzain by two different irreversible peptidyl halomethyl ketones (PHK)
      inhibitors has been studied by means of hybrid quantum mechanics/molecular
      mechanics-molecular dynamics (MD) simulations to obtain a complete representation
      of the possible free energy reaction paths. These have been traced on free energy
      surfaces in terms of the potential of mean force computed at AM1d/MM and DFT/MM
      levels of theory. An analysis of the possible reaction mechanisms of the
      inhibition process has been performed showing that the nucleophilic attack of an
      active site cysteine, Cys25, on a carbon atom of the inhibitor and the cleavage
      of the halogen-carbon bond take place in a single step. PClK appears to be much
      more favorable than PFK from a kinetic point of view. This result would be in
      agreement with experimental studies in other papain-like enzymes. A deeper
      analysis of the results suggests that the origin of the differences between PClK
      and PFK can be the different stabilizing interactions established between the
      inhibitors and the residues of the active site of the protein. Any attempt to
      explore the viability of the inhibition process through a stepwise mechanism
      involving the formation of a thiohemiketal intermediate and a three-membered
      sulfonium intermediate has been unsuccessful. Nevertheless, a mechanism through a
      protonated thiohemiketal, with participation of His159 as a proton donor, appears
      to be feasible despite showing higher free energy barriers. Our results suggest
      that PClK can be used as a starting point to develop a proper inhibitor of
      cruzain. 

PMID- 25965915
TI  - Incidence and Predictors of New-Onset Atrial Fibrillation in Septic Shock
      Patients in a Medical ICU: Data from 7-Day Holter ECG Monitoring.
AB  - PURPOSE: We investigated incidence, risk factors for new-onset atrial
      fibrillation (NAF), and prognostic impact during septic shock in medical
      Intensive Care Unit (ICU) patients. METHODS: Prospective, observational study in
      a university hospital. Consecutive patients from 03/2011 to 05/2013 with septic
      shock were eligible. Exclusion criteria were age <18 years, history of AF,
      transfer with prior septic shock. Included patients were equipped with long
      duration (7 days) Holter ECG monitoring. NAF was defined as an AF episode lasting
      >30 seconds. Patient characteristics, infection criteria, cardiovascular
      parameters, severity of illness, support therapies were recorded. RESULTS: Among
      66 patients, 29(44%) developed NAF; 10 (34%) would not have been diagnosed
      without Holter ECG monitoring. NAF patients were older, with more markers of
      heart failure (troponin and NT-pro-BNP), lower left ventricular ejection fraction
      (LVEF), longer QRS duration and more nonsustained supra ventricular arrhythmias
      (<30s) on day 1 than patients who maintained sinus rhythm. By multivariate
      analysis, age (OR: 1.06; p = 0.01) and LVEF<45% (OR: 13.01, p = 0.03) were
      associated with NAF. NAF did not predict 28 or 90 day mortality. CONCLUSIONS: NAF
      is common, especially in older patients, and is associated with low ejection
      fraction. We did not find NAF to be independently associated with higher
      mortality.

PMID- 25965916
TI  - Purification of functionalized DNA origami nanostructures.
AB  - The high programmability of DNA origami has provided tools for precise
      manipulation of matter at the nanoscale. This manipulation of matter opens up the
      possibility to arrange functional elements for a diverse range of applications
      that utilize the nanometer precision provided by these structures. However, the
      realization of functionalized DNA origami still suffers from imperfect production
      methods, in particular in the purification step, where excess material is
      separated from the desired functionalized DNA origami. In this article we
      demonstrate and optimize two purification methods that have not previously been
      applied to DNA origami. In addition, we provide a systematic study comparing the
      purification efficacy of these and five other commonly used purification methods.
      Three types of functionalized DNA origami were used as model systems in this
      study. DNA origami was patterned with either small molecules, antibodies, or
      larger proteins. With the results of our work we aim to provide a guideline in
      quality fabrication of various types of functionalized DNA origami and to provide
      a route for scalable production of these promising tools. 

PMID- 25965917
TI  - Long-term follow-up of 120 patients after hepaticojejunostomy for treatment of
      post-cholecystectomy bile duct injuries: A retrospective cohort study.
AB  - BACKGROUND: Long-term follow-up is essential for assessment of success of the
      surgical repair of post-cholecystectomy bile duct injuries (BDI). Factors
      affecting the long-term outcome and satisfactory length of follow-up have been
      little reported in the literature. The aim of this study is long-term evaluation
      of hepaticojejunostomy regarding clinical, radiological, laboratory and quality
      of life assessment. METHOD: Between January 1992 to December 2007, 120 patients
      with postcholecystectomy bile duct injury surgically treated by
      hepaticojejunostomy Roux-en-Y were followed up for 20 years in Mansoura Gastro
      enterology Center. Long-term outcomes and quality of life (QOL) were evaluated
      for all patients. Univariate and multivariate analyses were done for detection of
      factors affecting long-term outcome. RESULTS: The median follow up period was 149
      months, range (70-246 months). Successful long-term outcome was detected in 106
      (88.3%) patients. Long-term complications were detected in 35 (29%) patients.
      Fourteen (11.6%) patients developed anastomotic stricture within different follow
      up intervals up to 17 years, of which. Seventeen (14.2%) patients developed
      recurrent episodes of cholangitis at median interval 48 months, range (2-156
      months). Post-ERCP pancreatitis, number of anastomosis, operative time, post
      operative early complications, and post-operative bile leak were predictors for
      poor outcome. Physical component was much more affected than mental component in
      QOL. CONCLUSION: Management of BDI in specialized centers is highly recommended.
      Longer time for follow-up of the patients of surgical repair of bile duct injury
      up to 20 years should be adopted to ensure successful outcome. Quality of life
      assessment is essential component of long-term follow-up.

PMID- 25965918
TI  - Synthesis of Peptide-Based Hybrid Nanobelts with Enhanced Color Emission by Heat
      Treatment or Water Induction.
AB  - We demonstrate that an inorganic lanthanide ion (Tb(3+)) or organic dye molecules
      were encapsulated in situ into diphenylalanine (FF) organogels by a general,
      simple, and efficient co-assembly process, which generated peptide-based hybrid
      nanobelts with a range of colored emissions. In the presence of a photosensitizer
      (salicylic acid), the organogel can serve as an excellent molecular-donor
      scaffold to investigate FRET to Tb(3+). More importantly, heat treatment or water
      induction instigated a morphology transition from nanofibers to nanobelts, after
      which the participation of guest molecules in the FF assembly was promoted and
      the stability and photoluminescence emission of the composite organogels were
      enhanced.

PMID- 25965919
TI  - Anesthesia in flexible bronchoscopy - Randomized clinical trial comparing the use
      of topical lidocaine alone or in association with propofol, alfentnil or
      midazolam.

PMID- 25965920
TI  - The role of neutropenia on outcomes of cancer patients with community-acquired
      pneumonia.

PMID- 25965921
TI  - Anxiety and depression in COPD: Current understanding, unanswered questions, and
      research needs.

PMID- 25965922
TI  - COPD as a disease of accelerated lung aging(a).

PMID- 25965923
TI  - Efficacy of percutaneous versus intradermal BCG in the prevention of tuberculosis
      in South Africa infants: Randomised trial.

PMID- 25965924
TI  - Brazilian experience in the management of multidrug-resistance.
AB  - In this article the author reviews the evolution of the approach to multidrug
      resistant tuberculosis (MDR-TB) in Brazil following the introduction of
      rifampicin associated to isoniazid and pyrazinamide (RHZ). It shows Brazil was
      one of the world's first countries to use the RHZ regimen within a treatment
      system, with a first line regimen, another one specific for meningo-encephalic
      forms, for re-treatment of recurrences or of patients who returned with active
      tuberculosis after abandoning treatment, and a reserve regimen. The system was
      applied nationwide with guaranteed cost-free provision of medication, and self
      administered. The author evaluates the growth of drug resistance, the emergence
      of multidrug-resistance and how management of this form of the disease has been
      organised. 

PMID- 25965925
TI  - Evolutionary forces in Mycobacterium tuberculosis.

PMID- 25965926
TI  - Epidemiology and ecology of nontuberculous mycobacteria.

PMID- 25965928
TI  - Regulation of Mycobacterium tuberculosis cell wall lipid composition and its
      effects on in vitro bacterial persistence.

PMID- 25965927
TI  - The use of interferon gamma release assays as an aid in the control of
      tuberculosis.

PMID- 25965929
TI  - A new live tuberculosis vaccine based on phoP inactivation.

PMID- 25965930
TI  - Symposium: Point-of-care tests for tuberculosis.

PMID- 25965931
TI  - Introduction.

PMID- 25965932
TI  - Building tuberculosis laboratory capacity: Needs and strategies.

PMID- 25965933
TI  - The experience of the Brazilian Tuberculosis Research Network in the development
      and evaluation of new methods of diagnosing tuberculosis.

PMID- 25965934
TI  - Tuberculosis in portugal.

PMID- 25965935
TI  - Clinical trials of new tuberculosis drugs and diagnostic tests:
      Mycobacteriological challenges.

PMID- 25965936
TI  - Screening of molecules with anti-TB activity from the brazilian cerrado plants.

PMID- 25965937
TI  - New, easy-to-use tools for standardised and quality-controlled genotyping of
      Mycobacterium tuberculosis complex strains.

PMID- 25965938
TI  - Symposium: External quality assurance.

PMID- 25965939
TI  - Interpretive Diagnostic Error Reduction in Surgical Pathology and Cytology:
      Guideline From the College of American Pathologists Pathology and Laboratory
      Quality Center and the Association of Directors of Anatomic and Surgical
      Pathology.
AB  - CONTEXT: Additional reviews of diagnostic surgical and cytology cases have been
      shown to detect diagnostic discrepancies. OBJECTIVE: To develop, through a
      systematic review of the literature, recommendations for the review of pathology
      cases to detect or prevent interpretive diagnostic errors. DESIGN: The College of
      American Pathologists Pathology and Laboratory Quality Center in association with
      the Association of Directors of Anatomic and Surgical Pathology convened an
      expert panel to develop an evidence-based guideline to help define the role of
      case reviews in surgical pathology and cytology. A literature search was
      conducted to gather data on the review of cases in surgical pathology and
      cytology. RESULTS: The panel drafted 5 recommendations, with strong agreement
      from open comment period participants ranging from 87% to 93%. The
      recommendations are: (1) anatomic pathologists should develop procedures for the
      review of selected pathology cases to detect disagreements and potential
      interpretive errors; (2) anatomic pathologists should perform case reviews in a
      timely manner to avoid having a negative impact on patient care; (3) anatomic
      pathologists should have documented case review procedures that are relevant to
      their practice setting; (4) anatomic pathologists should continuously monitor and
      document the results of case reviews; and (5) if pathology case reviews show poor
      agreement within a defined case type, anatomic pathologists should take steps to
      improve agreement. CONCLUSIONS: Evidence exists that case reviews detect errors;
      therefore, the expert panel recommends that anatomic pathologists develop
      procedures for the review of pathology cases to detect disagreements and
      potential interpretive errors, in order to improve the quality of patient care.

PMID- 25965940
TI  - Activity of Krebs cycle enzymes in mdx mice.
AB  - INTRODUCTION: Duchenne muscular dystrophy (DMD) is a degenerative disease of
      skeletal, respiratory, and cardiac muscles caused by defects in the dystrophin
      gene. More recently, brain involvement has been verified. Mitochondrial
      dysfunction and oxidative stress may underlie the pathophysiology of DMD. In this
      study we evaluate Krebs cycle enzymes activity in the cerebral cortex, diaphragm,
      and quadriceps muscles of mdx mice. METHODS: Cortex, diaphragm, and quadriceps
      tissues from male dystrophic mdx and control mice were used. RESULTS: We observed
      increased malate dehydrogenase activity in the cortex; increased malate
      dehydrogenase and succinate dehydrogenase activities in the diaphragm; and
      increased citrate synthase, isocitrate dehydrogenase, and malate dehydrogenase
      activities in the quadriceps of mdx mice. CONCLUSION: This study showed increased
      activity of Krebs cycle enzymes in cortex, quadriceps, and diaphragm in mdx mice.

PMID- 25965941
TI  - A robust superconducting setup to probe the thermal Casimir effect.
AB  - We describe a superconducting Casimir apparatus inspired by a recently proposed
      setup involving magnetic surfaces (Bimonte G 2014 Phys. Rev. Lett. 112 240401).
      The present setup consists of a superconducting Nb sphere and a flat gold plate
      including in its interior a superconducting Nb strip. The experimental scheme
      involves a differential measurement of the Casimir force at a point of the gold
      plate above the Nb strip and away from it. We show that similar to the previous
      setup, the superconducting system considered here implies widely different
      modulations of the Casimir force, depending on whether the thermal force is
      computed using the Drude or the plasma model, thus paving the way to an
      unambiguous discrimination between these alternative prescriptions. 

PMID- 25965942
TI  - Feeling of control of an action after supra and subliminal haptic distortions.
AB  - Here we question the mechanisms underlying the emergence of the feeling of
      control that can be modulated even when the feeling of being the author of one's
      own action is intact. With a haptic robot, participants made series of vertical
      pointing actions on a virtual surface, which was sometimes postponed by a small
      temporal delay (15 or 65 ms). Subjects then evaluated their subjective feeling of
      control. Results showed that after temporal distortions, the hand-trajectories
      were adapted effectively but that the feeling of control decreased significantly.
      This was observed even in the case of subliminal distortions for which subjects
      did not consciously detect the presence of a distortion. Our findings suggest
      that both supraliminal and subliminal temporal distortions that occur within a
      healthy perceptual-motor system impact the conscious experience of the feeling of
      control of self-initiated motor actions.

PMID- 25965943
TI  - Using continual flash suppression to investigate cognitive aftereffects.
AB  - In a naming task with visually presented words, Prioli and Kahan (2015) reported
      that negatively valenced words were identified more slowly than neutral words in
      a condition with continual flash suppression (CFS), which involves showing the
      dominant eye changing Mondrian patterns, delaying awareness for the word shown to
      the other eye. However, when these same words were shown to both eyes (i.e., no
      CFS), negatively valenced words were identified more quickly. The authors
      hypothesized that the negative word deficit with CFS reflects greater habituation
      (i.e., a cognitive aftereffect) that accrues for negative words before the
      observer becomes aware of the word. However, aftereffects typically occur in
      response to a target stimulus that follows an adapting stimulus, rather than in
      response to a single stimulus that is initially processed without awareness.
      Thus, it is not immediately obvious that the explanation provided by Prioli and
      Kahan is adequate. Here I report a simulation using a model that was previously
      applied to cognitive aftereffects, demonstrating that their account can explain
      this crossover interaction. These results suggest that CFS may be a useful
      technique for studying cognitive aftereffects without concern for conscious
      decision strategies. 

PMID- 25965944
TI  - Deterministic control of broadband light through a multiply scattering medium via
      the multispectral transmission matrix.
AB  - We present a method to measure the spectrally-resolved transmission matrix of a
      multiply scattering medium, thus allowing for the deterministic spatiospectral
      control of a broadband light source by means of wavefront shaping. As a
      demonstration, we show how the medium can be used to selectively focus one or
      many spectral components of a femtosecond pulse, and how it can be turned into a
      controllable dispersive optical element to spatially separate different spectral
      components to arbitrary positions. 

PMID- 25965945
TI  - Ultrasmall TiO2 Nanoparticles in Situ Growth on Graphene Hybrid as Superior Anode
      Material for Sodium/Lithium Ion Batteries.
AB  - To inhibit the aggregation of TiO2 nanoparticles and to improve the
      electrochemical kinetics of TiO2 electrode, a hybrid material of ultrasmall TiO2
      nanoparticles in situ grown on rGO nanosheets was obtained by ultraphonic and
      reflux methods. The size of the TiO2 particles was controlled about 10 nm, and
      these particles were evenly distributed across the rGO nanosheets. When used for
      the anode of a sodium ion battery, the electrochemical performance of this hybrid
      TiO2@rGO was much improved. A capacity of 186.6 mAh g(-1) was obtained after 100
      cycles at 0.1 A g(-1), and 112.2 mAh g(-1) could be maintained at 1.0 A g(-1),
      showing a high capacity and good rate capability. On the basis of the analysis of
      cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), the
      achieved excellent electrochemical performance was mainly attributed to the
      synergetic effect of well-dispersed ultrasmall TiO2 nanoparticles and conductive
      graphene network and the improved electrochemical kinetics. The superior
      electrochemical performance of this hybrid material on lithium storage further
      confirmed the positive effect of rGO. 

PMID- 25965946
TI  - Type II spiral ganglion afferent neurons drive medial olivocochlear reflex
      suppression of the cochlear amplifier.
AB  - The dynamic adjustment of hearing sensitivity and frequency selectivity is
      mediated by the medial olivocochlear efferent reflex, which suppresses the gain
      of the 'cochlear amplifier' in each ear. Such efferent feedback is important for
      promoting discrimination of sounds in background noise, sound localization and
      protecting the cochleae from acoustic overstimulation. However, the sensory
      driver for the olivocochlear reflex is unknown. Here, we resolve this
      longstanding question using a mouse model null for the gene encoding the type III
      intermediate filament peripherin (Prph). Prph((-/-)) mice lacked type II spiral
      ganglion neuron innervation of the outer hair cells, whereas innervation of the
      inner hair cells by type I spiral ganglion neurons was normal. Compared with
      Prph((+/+)) controls, both contralateral and ipsilateral olivocochlear efferent
      mediated suppression of the cochlear amplifier were absent in Prph((-/-)) mice,
      demonstrating that outer hair cells and their type II afferents constitute the
      sensory drive for the olivocochlear efferent reflex. 

PMID- 25965947
TI  - Expression of the Carboxy-Terminal Portion of MUC16/CA125 Induces Transformation
      and Tumor Invasion.
AB  - The CA125 antigen is found in the serum of many patients with serous ovarian
      cancer and has been widely used as a disease marker. CA125 has been shown to be
      an independent factor for clinical outcome in this disease. In The Cancer Genome
      Atlas ovarian cancer project, MUC16 expression levels are frequently increased,
      and the highest levels of MUC16 expression are linked to a significantly worse
      survival. To examine the biologic effect of the proximal portion of MUC16/CA125,
      NIH/3T3 (3T3) fibroblast cell lines were stably transfected with the carboxy
      elements of MUC16. As few as 114 amino acids from the carboxy-terminal portion of
      MUC16 were sufficient to increase soft agar growth, promote matrigel invasion,
      and increase the rate of tumor growth in athymic nude mice. Transformation with
      carboxy elements of MUC16 was associated with activation of the AKT and ERK
      pathways. MUC16 transformation was associated with up-regulation of a number of
      metastases and invasion gene transcripts, including IL-1beta, MMP2, and MMP9. All
      observed oncogenic changes were exclusively dependent on the extracellular
      "ectodomain" of MUC16. The biologic impact of MUC16 was also explored through the
      creation of a transgenic mouse model expressing 354 amino acids of the carboxy
      terminal portion of MUC16 (MUC16c354). Under a CMV, early enhancer plus chicken
      beta actin promoter (CAG) MUC16c354 was well expressed in many organs, including
      the brain, colon, heart, kidney, liver, lung, ovary, and spleen. MUC16c354
      transgenic animals appear to be viable, fertile, and have a normal lifespan.
      However, when crossed with p53-deficient mice, the MUC16c354:p53+/- progeny
      displayed a higher frequency of spontaneous tumor development compared to p53+/-
      mice alone. We conclude that the carboxy-terminal portion of the MUC16/CA125
      protein is oncogenic in NIH/3T3 cells, increases invasive tumor properties,
      activates the AKT and ERK pathways, and contributes to the biologic properties of
      ovarian cancer. 

PMID- 25965948
TI  - Utilizing a high-throughput microfluidic platform to study hypoxia-driven
      mesenchymal-mode cell migration.
AB  - Hypoxia is a critical microenvironment in tumor pathogenesis. There is a close
      relationship between hypoxia, tumor metastasis and poor prognosis. Hypoxia has
      been shown to induce epithelial-mesenchymal transition and high levels of lactic
      acid production, through which cancer cells gain migratory capability. Here, we
      present a high-throughput microfluidic platform with a controlled oxygen
      environment to specifically monitor mesenchymal migration under hypoxic
      conditions. We found that, combined with a slightly alkaline microenvironment,
      such a platform can help to improve the efficiency of antimetastatic drugs. We
      also use this platform to study primary and rare cells from mice and demonstrate
      the correlation between on-chip results and in vivo outcome. This device may
      provide a new opportunity for biologists and clinicians to better perform assays
      that evaluate cancer cell behaviors related to metastasis. 

PMID- 25965949
TI  - Efficient acetone-butanol-ethanol production by Clostridium beijerinckii from
      sugar beet pulp.
AB  - Sugar beet pulp (SBP) has been investigated as a promising feedstock for ABE
      fermentation by Clostridium beijerinckii. Although lignin content in SBP is low,
      a pretreatment is needed to enhance enzymatic hydrolysis and fermentation yields.
      Autohydrolysis at pH 4 has been selected as the best pretreatment for SBP in
      terms of sugars release and acetone and butanol production. The best overall
      sugars release yields from raw SBP ranged from 66.2% to 70.6% for this
      pretreatment. The highest ABE yield achieved was 0.4g/g (5.1g/L of acetone and
      6.6g/L butanol) and 143.2g ABE/kg SBP (62.3g acetone and 80.9g butanol) were
      obtained when pretreated SBP was enzymatically hydrolyzed at 7.5% (w/w) solid
      loading. Higher solid loadings (10%) offered higher acetone and butanol titers
      (5.8g/L of acetone and 7.8g/L butanol). All the experiments were carried out
      under not-controlling pH conditions reaching about 5.3 in the final samples. 

PMID- 25965950
TI  - Effects of simulated flue gas on components of Scenedesmus raciborskii WZKMT.
AB  - Scenedesmus raciborskii WZKMT cultured with simulated flue gas was investigated.
      Cellular components, including total sugar, starch, chlorophyll, protein and
      lipid, were compared between simulated flue gas and 7% (v/v) CO2. Dissolution of
      SO2 and NO in simulated flue gas led to pH decrease and toxicity to microalgae
      cells. Furthermore, the death or aging of microalgae cells reduced the buffer
      capacity and caused decrease of simulated flue gas absorption. With 7% CO2, the
      highest total sugar and starch content could attain to 66.76% and 53.16%,
      respectively, which indicated S. raciborskii WZKMT is a desired feedstock
      candidate for bioethanol production. Microalgae growth and starch accumulation
      was inhibited, while cells produced more chlorophyll, protein and lipid when
      simulated flue gas was the carbon source. Fatty acids composition analysis
      indicated that there was no significant distinction on fatty acids relative
      content (fatty acid/TFA) between cells aerated using simulated flue gas and 7%
      CO2. 

PMID- 25965951
TI  - Startup and oxygen concentration effects in a continuous granular mixed flow
      autotrophic nitrogen removal reactor.
AB  - The startup and performance of the completely autotrophic nitrogen removal over
      nitrite (CANON) process was tested in a continuously fed granular bubble column
      reactor (BCR) with two different aeration strategies: controlling the oxygen
      volumetric flow and oxygen concentration. During the startup with the control of
      oxygen volumetric flow, the air volume was adjusted to 60mL/h and the CANON
      reactor had volumetric N loadings ranging from 7.35 to 100.90mgN/Ld with 36-71%
      total nitrogen removal and high instability. In the second stage, the reactor was
      operated at oxygen concentrations of 0.6, 0.4 and 0.2mg/L. The best condition was
      0.2 mgO2/L with a total nitrogen removal of 75.36% with a CANON reactor activity
      of 0.1149gN/gVVSd and high stability. The feasibility and effectiveness of CANON
      processes with oxygen control was demonstrated, showing an alternative design
      tool for efficiently removing nitrogen species. 

PMID- 25965952
TI  - Biomass viability: An experimental study and the development of an empirical
      mathematical model for submerged membrane bioreactor.
AB  - This study investigates the influence of key biomass parameters on specific
      oxygen uptake rate (SOUR) in a sponge submerged membrane bioreactor (SSMBR) to
      develop mathematical models of biomass viability. Extra-cellular polymeric
      substances (EPS) were considered as a lumped parameter of bound EPS (bEPS) and
      soluble microbial products (SMP). Statistical analyses of experimental results
      indicate that the bEPS, SMP, mixed liquor suspended solids and volatile suspended
      solids (MLSS and MLVSS) have functional relationships with SOUR and their
      relative influence on SOUR was in the order of EPS>bEPS>SMP>MLVSS/MLSS. Based on
      correlations among biomass parameters and SOUR, two independent empirical models
      of biomass viability were developed. The models were validated using results of
      the SSMBR. However, further validation of the models for different operating
      conditions is suggested. 

PMID- 25965953
TI  - Semi-continuous mesophilic anaerobic digester performance under variations in
      solids retention time and feeding frequency.
AB  - The goal of this research was to understand the effect of solids retention time
      (SRT) and feeding frequency on the performance of anaerobic digesters used to
      recover bioenergy from swine waste. Semi-continuous mesophilic anaerobic
      digesters were operated at varying SRTs and feeding frequencies. Performance
      metrics included biogas and methane production rates, biomass robustness and
      functionality and removals of volatile solids, soluble chemical oxygen demand,
      the fecal-indicator bacteria Escherichia coli, and the human pathogen Salmonella.
      Biochemical methane formation potential and specific methanogenic activity assays
      were used to demonstrate biomass robustness and functionality. Results indicated
      that anaerobic digesters fed weekly had higher average methane yields (0.20 vs.
      0.18m(3)CH4/kg-VSadded), specific methanogenic activities (40 vs. 35ml/day), and
      fecal indicator bacteria destruction (99.9% vs. 99.4%) than those fed every-other
      day. Salmonella, soluble COD, and VS destruction did not change with varied
      feeding frequency; however, higher removals were observed with longer SRT. 

PMID- 25965954
TI  - Enhancing the response of microbial fuel cell based toxicity sensors to Cu(II)
      with the applying of flow-through electrodes and controlled anode potentials.
AB  - The application of microbial fuel cell (MFC)-based toxicity sensors to real-world
      water monitoring is partly impeded by the limited sensitivity. To address this
      limitation, this study optimized the flow configurations and the control modes.
      Results revealed that the sensitivity increased by ~15-41times with the applying
      of a flow-through anode, compared to those with a flow-by anode. The sensors
      operated in the controlled anode potential (CP) mode delivered better sensitivity
      than those operated in the constant external resistance (ER) mode over a broad
      range of anode potentials from -0.41V to +0.1V. Electrodeposition of Cu(II) was
      found to bias the toxicity measurement at low anode potentials. The optimal anode
      potential was approximately -0.15V, at which the sensor achieved an unbiased
      measurement of toxicity and the highest sensitivity. This value was greater than
      those required for electrodeposition while smaller than those for power
      overshoot. 

PMID- 25965955
TI  - An Improved and Efficient Process for the Preparation of (+)-cloprostenol.
AB  - An improved and efficient synthesis of (+)-cloprostenol has been accomplished in
      nine steps and 26% overall yield from commercially available (-)-Corey lactone 4
      phenylbenzoate alcohol . The present route avoids tedious purifications and
      requires only one column chromatography operation, which reduces the generation
      of waste and is suitable for large-scale preparation.

PMID- 25965956
TI  - A temperature-monitoring vaginal ring for measuring adherence.
AB  - BACKGROUND: Product adherence is a pivotal issue in the development of effective
      vaginal microbicides to reduce sexual transmission of HIV. To date, the six Phase
      III studies of vaginal gel products have relied primarily on self-reporting of
      adherence. Accurate and reliable methods for monitoring user adherence to
      microbicide-releasing vaginal rings have yet to be established. METHODS: A
      silicone elastomer vaginal ring prototype containing an embedded, miniature
      temperature logger has been developed and tested in vitro and in cynomolgus
      macaques for its potential to continuously monitor environmental temperature and
      accurately determine episodes of ring insertion and removal. RESULTS: In vitro
      studies demonstrated that DST nano-T temperature loggers encapsulated in medical
      grade silicone elastomer were able to accurately and continuously measure
      environmental temperature. The devices responded quickly to temperature changes
      despite being embedded in different thickness of silicone elastomer. Prototype
      vaginal rings measured higher temperatures compared with a subcutaneously
      implanted device, showed high sensitivity to diurnal fluctuations in vaginal
      temperature, and accurately detected periods of ring removal when tested in
      macaques. CONCLUSIONS: Vaginal rings containing embedded temperature loggers may
      be useful in the assessment of product adherence in late-stage clinical trials.

PMID- 25965957
TI  - Will "Combined Prevention" Eliminate Racial/Ethnic Disparities in HIV Infection
      among Persons Who Inject Drugs in New York City?
AB  - It has not been determined whether implementation of combined prevention
      programming for persons who inject drugs reduce racial/ethnic disparities in HIV
      infection. We examine racial/ethnic disparities in New York City among persons
      who inject drugs after implementation of the New York City Condom Social
      Marketing Program in 2007. Quantitative interviews and HIV testing were conducted
      among persons who inject drugs entering Mount Sinai Beth Israel drug treatment
      (2007-2014). 703 persons who inject drugs who began injecting after
      implementation of large-scale syringe exchange were included in the analyses.
      Factors independently associated with being HIV seropositive were identified and
      a published model was used to estimate HIV infections due to sexual transmission.
      Overall HIV prevalence was 4%; Whites 1%, African-Americans 17%, and Hispanics
      4%. Adjusted odds ratios were 21.0 (95% CI 5.7, 77.5) for African-Americans to
      Whites and 4.5 (95% CI 1.3, 16.3) for Hispanics to Whites. There was an overall
      significant trend towards reduced HIV prevalence over time (adjusted odd ratio =
      0.7 per year, 95% confidence interval (0.6-0.8). An estimated 75% or more of the
      HIV infections were due to sexual transmission. Racial/ethnic disparities among
      persons who inject drugs were not significantly different from previous
      disparities. Reducing these persistent disparities may require new interventions
      (treatment as prevention, pre-exposure prophylaxis) for all racial/ethnic groups.

PMID- 25965958
TI  - Highly Stereoselective Synthesis of Lamivudine (3TC) and Emtricitabine (FTC) by a
      Novel N-Glycosidation Procedure.
AB  - The combined use of silanes (Et3SiH or PMHS) and I2 as novel N-glycosidation
      reagents for the synthesis of bioactive oxathiolane nucleosides 3TC and FTC is
      reported. Both systems (working as anhydrous HI sources) were devised to act as
      substrate activators and N-glycosidation promoters. Excellent results in terms of
      chemical efficiency and stereoselectivity of the reactions were obtained;
      surprisingly, the nature of the protective group at the N4 position of
      (fluoro)cytosine additionally influenced the stereochemical reaction outcome. 

PMID- 25965959
TI  - Pancreatic Islet APJ Deletion Reduces Islet Density and Glucose Tolerance in
      Mice.
AB  - Protection and replenishment of a functional pancreatic beta-cell mass (BCM) are
      key goals of all diabetes therapies. Apelin, a small regulatory peptide, is the
      endogenous ligand for the apelin receptor (APJ) receptor. The apelin-APJ
      signaling system is expressed in rodent and human islet cells. Apelin exposure
      has been shown to inhibit and to stimulate insulin secretion. Our aim was to
      assess the influence of a selective APJ deletion in pancreatic islet cells on
      islet homeostasis and glucose tolerance in mice. Cre-LoxP strategy was utilized
      to mediate islet APJ deletion. APJ deletion in islet cells (APJ(Deltaislet))
      resulted in a significantly reduced islet size, density and BCM. An ip glucose
      tolerance test showed significantly impaired glucose clearance in APJ(Deltaislet)
      mice. APJ(Deltaislet) mice were not insulin resistant and in vivo glucose
      stimulated insulin secretion was reduced modestly. In vitro glucose-stimulated
      insulin secretion showed a significantly reduced insulin secretion by islets from
      APJ(Deltaislet) mice. Glucose clearance in response to ip glucose tolerance test
      in obese APJ(Deltaislet) mice fed a chronic high-fat (HF) diet, but not pregnant
      APJ(Deltaislet) mice, was impaired significantly. In addition, the obesity
      induced adaptive elevations in mean islet size and fractional islet area were
      reduced significantly in obese APJ(Deltaislet) mice when compared with wild-type
      mice. Together, these findings demonstrate a stimulatory role for the islet cell
      apelin-APJ signaling axis in regulation of pancreatic islet homeostasis and in
      metabolic induced beta-cell hyperplasia. The results indicate the apelin-APJ
      system can be exploited for replenishment of BCM. 

PMID- 25965961
TI  - Study on the active mechanism of beta-secretase inhibitors by molecular
      simulations.
AB  - The proteolytic enzyme beta-secretase (BACE-1) is one of potential drug targets
      for treating Alzheimers's disease. First, the reliable and accurate models of
      three-dimensional quantitative structure-activity relationship for the BACE-1
      inhibitors were established, and the several important structural factors that
      mainly influence the inhibitory activity were obtained. Second, the results of
      molecular docking presented the binding mode between BACE-1 and its inhibitors,
      and molecular dynamic simulations provided the details of the receptor-ligand
      interactions. Furthermore, several new derivatives were designed and validated
      based on these theoretical analyses. Our studies revealed the binding mechanism
      between BACE-1 and its inhibitors, and provide some insights into the further
      structural modification and the design of new inhibitors with higher activity. 

PMID- 25965960
TI  - Dopaminergic Neurons Controlling Anterior Pituitary Functions: Anatomy and
      Ontogenesis in Zebrafish.
AB  - Dopaminergic (DA) neurons located in the preoptico-hypothalamic region of the
      brain exert a major neuroendocrine control on reproduction, growth, and
      homeostasis by regulating the secretion of anterior pituitary (or
      adenohypophysis) hormones. Here, using a retrograde tract tracing experiment, we
      identified the neurons playing this role in the zebrafish. The DA cells
      projecting directly to the anterior pituitary are localized in the most
      anteroventral part of the preoptic area, and we named them preoptico-hypophyseal
      DA (POHDA) neurons. During development, these neurons do not appear before 72
      hours postfertilization (hpf) and are the last dopaminergic cell group to
      differentiate. We found that the number of neurons in this cell population
      continues to increase throughout life proportionally to the growth of the fish. 5
      Bromo-2'-deoxyuridine incorporation analysis suggested that this increase is due
      to continuous neurogenesis and not due to a phenotypic change in already-existing
      neurons. Finally, expression profiles of several genes (foxg1a, dlx2a, and
      nr4a2a/b) were different in the POHDA compared with the adjacent suprachiasmatic
      DA neurons, suggesting that POHDA neurons develop as a distinct DA cell
      population in the preoptic area. This study offers some insights into the
      regional identity of the preoptic area and provides the first bases for future
      functional genetic studies on the development of DA neurons controlling anterior
      pituitary functions. 

PMID- 25965962
TI  - K(V)7.4 channels participate in the control of rodent renal vascular resting
      tone.
AB  - AIM: We tested the hypothesis that K(V)7 channels contribute to basal renal
      vascular tone and that they participate in agonist-induced renal vasoconstriction
      or vasodilation. METHODS: KV 7 channel subtypes in renal arterioles were
      characterized by immunofluorescence. Renal blood flow (RBF) was measured using an
      ultrasonic flow probe. The isometric tension of rat interlobar arteries was
      examined in a wire myograph. Mice afferent arteriolar diameter was assessed
      utilizing the perfused juxtamedullary nephron technique. RESULTS:
      Immunofluorescence revealed that K(V)7.4 channels were expressed in rat afferent
      arterioles. The K(V)7 blocker XE991 dose-dependently increased the isometric
      tension of rat interlobar arteries and caused a small (approx. 4.5%) RBF
      reduction in vivo. Nifedipine abolished these effects. Likewise, XE991 reduced
      mouse afferent arteriolar diameter by approx. 5%. The K(V)7.2-5 stimulator
      flupirtine dose-dependently relaxed isolated rat interlobar arteries and
      increased (approx. 5%) RBF in vivo. The RBF responses to NE or Ang II
      administration were not affected by pre-treatment with XE991 or flupirtine. XE991
      pre-treatment caused a minor augmentation of the acetylcholine-induced increase
      in RBF, while flupirtine pre-treatment did not affect this response. CONCLUSION:
      It is concluded that K(V)7 channels, via nifedipine sensitive channels, have a
      role in the regulation of basal renal vascular tone. There is no indication that
      K(V)7 channels have an effect on agonist-induced renal vasoconstriction while
      there is a small effect on acetylcholine-induced vasodilation.

PMID- 25965963
TI  - Assessment of infection in chronic wounds based on the activities of elastase,
      lysozyme and myeloperoxidase.

PMID- 25965964
TI  - Chloride-induced shape transformation of silver nanoparticles in a water
      environment.
AB  - The effects of chloride on dissolution and toxicity of silver nanoparticles
      (AgNPs) have been well studied. However, their intermediate shapes during the
      transition have not been illustrated to-date. Herein, the chloride-induced shape
      transformation process of AgNPs under long-term, low-concentration conditions is
      explored. A unique triangular Ag-AgCl heterostructure is observed. The structure
      then evolves into a symmetric hexapod and finally into a smaller AgNP. This
      transformation process could be affected by other environmental conditions, such
      as 0.4 mg/mL humic acid, 5% surfactants and 1 mg/mL bovine serum albumin protein.
      Our results offer new knowledge regarding the shape transformation process of
      AgNPs in the presence of chloride, which can be valuable in relevant studies
      concerning the effect of water chemistry on the behavior of AgNPs. 

PMID- 25965965
TI  - Effects of dietary potato by-product and rumen-protected histidine on growth,
      carcass characteristics and quality attributes of beef.
AB  - We hypothesized that variable composition in finishing rations, more
      specifically; the proportion of potato-by-product (PBP) and rumen protected
      histidine (His) supplementation may influence growth and meat quality attributes.
      Two different diets were fed (1) finishing ration with corn and barley as grains
      (CB, n = 20) and (2) substitution of 10% corn, DM basis, with PBP (PBP, n = 20).
      Additionally, half of each dietary treatment received 50 g/hd/d rumen protected
      His (HS, n= 20) while the other half received no supplement (NS, n = 20).
      Inclusion of 10% PBP or HS did not affect growth or carcass traits. Color
      stability was analyzed using Hunter color values as well as AMSA visual appraisal
      in both longissimus thoracis (LT) and gluteus medius (GM) muscles. The LT, but
      not the GM, of CB steers was more color stable over a 9 d simulated retail
      display compared to those fed a PB diet. Steers receiving HS produced
      significantly (P < 0.05) more color stable LT and GM steaks.

PMID- 25965966
TI  - The effect of partial-fat substitutions with encapsulated and unencapsulated fish
      oils on the technological and eating quality of beef burgers over storage.
AB  - The effects of fat substitution (<= 15%) with commercial encapsulated and
      unencapsulated fish oils on the technological and eating quality of beef burgers
      over storage [modified atmosphere packs (80% O2:20% CO2); constantly illuminated
      retail display at 4  degrees C; for 15 days] were studied using design of
      experiment (DOE). Burger formulations comprised beef shin (59.5%), salt (0.5%),
      vitamin E (0.015%) combined with varying levels of beef-fat/fish oils depending
      on the treatment. Increasing amounts of encapsulated and unencapsulated fish oils
      in burgers increased polyunsaturated fatty acid content (P < 0.001). Storage
      decreased (P < 0.001) a* values, which was in agreement with oxymyoglobin data.
      Vitamin E inclusion in burgers resulted in higher (P < 0.01) oxymyoglobin values.
      TBARS values increased (P < 0.001) over storage as expected. Fat substitution
      with unencapsulated oils increased cook loss (P < 0.001) and decreased hardness
      (P < 0.05) compared to other treatments. Optimisation predicted a burger
      formulation with 7.8% substitution in beef-fat with encapsulated fish oil.
      Panellists scored the optimised burger formulation (P < 0.05) lower than controls
      for overall acceptability.

PMID- 25965967
TI  - A mild and facile synthesis of polyfunctionalized pyridines: merging three
      component cyclization and aerobic oxidation by amine/metal catalysts.
AB  - A mild and facile synthesis of polyfunctionalized pyridines from NH4OAc,
      beta,gamma-unsaturated alpha-ketoesters, and ketones/aldehydes has been reported
      through tandem three-component cyclization and aerobic oxidation using the
      combination of amine and metal catalysts. The synthetic value of the developed
      methodology was demonstrated by a gram-scale reaction and a wide range of
      substrates including naturally occurring citronellal. 

PMID- 25965968
TI  - Function of cancer associated genes revealed by modern univariate and
      multivariate association tests.
AB  - Copy number variation (CNV) plays a role in pathogenesis of many human diseases,
      especially cancer. Several whole genome CNV association studies have been
      performed for the purpose of identifying cancer associated CNVs. Here we
      undertook a novel approach to whole genome CNV analysis, with the goal being
      identification of associations between CNV of different genes (CNV-CNV) across 60
      human cancer cell lines. We hypothesize that these associations point to the
      roles of the associated genes in cancer, and can be indicators of their position
      in gene networks of cancer-driving processes. Recent studies show that gene
      associations are often non-linear and non-monotone. In order to obtain a more
      complete picture of all CNV associations, we performed omnibus univariate
      analysis by utilizing dCov, MIC, and HHG association tests, which are capable of
      detecting any type of association, including non-monotone relationships. For
      comparison we used Spearman and Pearson association tests, which detect only
      linear or monotone relationships. Application of dCov, MIC and HHG tests resulted
      in identification of twice as many associations compared to those found by
      Spearman and Pearson alone. Interestingly, most of the new associations were
      detected by the HHG test. Next, we utilized dCov's and HHG's ability to perform
      multivariate analysis. We tested for association between genes of unknown
      function and known cancer-related pathways. Our results indicate that
      multivariate analysis is much more effective than univariate analysis for the
      purpose of ascribing biological roles to genes of unknown function. We conclude
      that a combination of multivariate and univariate omnibus association tests can
      reveal significant information about gene networks of disease-driving processes.
      These methods can be applied to any large gene or pathway dataset, allowing more
      comprehensive analysis of biological processes. 

PMID- 25965970
TI  - The effects of cancer on older workers in the English labour market.
AB  - The continued rise in overall cancer survival rates has ignited a field of
      research which examines the effect that cancer has on survivors' employment.
      Previous estimates of the effect of cancer on labour market outcomes, using U.S.
      data, show significant reductions in employment in the first 6 months after
      diagnosis. However, this impact has been found to dissipate after 12 and 18
      months. I use data from the English Longitudinal Study of Ageing and find that,
      in England, where there is a more generous welfare support system, not only does
      cancer have a negative impact in the first 6-month period following diagnosis,
      but also in the second 6-month period. I estimate that, in the second 6-month
      period after diagnosis, respondents with cancer are 12.2% points less likely to
      work and work 4.2 fewer hours a week when compared to matched, healthy controls.
      This suggests that the negative effects from cancer can persist for longer than
      the six months identified previously. These results have implications for
      government policy and employers, because it increases the length of time that
      survivors may be on government supported sick pay, and the expected time that
      workers will be absent from work due to illness. 

PMID- 25965971
TI  - Identification and Quantification of Flavonoids from Two Southern Italian
      Cultivars of Allium cepa L., Tropea (Red Onion) and Montoro (Copper Onion), and
      Their Capacity to Protect Human Erythrocytes from Oxidative Stress.
AB  - Onions (Allium cepa) are consumed worldwide and represent an important source of
      dietary phytochemicals with proven antioxidant properties, such as phenolic
      acids, flavonoids, thiosulfinates, and anthocyanins. Epidemiological and
      experimental data suggest that regular consumption of onions is associated with a
      reduced risk of degenerative disorders. Therefore, it is of interest to
      investigate the biological properties of different varieties of onions. Here, we
      characterized for the first time a variety of onion, called Ramata di Montoro
      (coppery onion from Montoro), grown in a niche area in southern Italy, and
      compared its phenolic profile and antioxidant properties to a commercial ecotype
      of red onion, Tropea, also present in southern Italy. An analytical method based
      on high-performance liquid chromatography coupled with UV detection and mass
      spectrometry was used to separate and characterize the phenolic fraction
      (anthocyanins and flavonols) extracted from both coppery and red types. The main
      compounds detected in the two ecotypes were quercetin and quercetin glucosides,
      isorhamnetin glucosides, kaempferol glucoside, and, among anthocyanins, cyanidin
      glucosides. Tropea ecotype onion showed a higher content of flavonols (632.82
      mg/kg fresh weight) than Montoro type onion (252.91 mg/kg fresh weight).
      Accordingly, the antioxidant activity of the former was 2.8-fold higher compared
      to the latter. More pronounced were the differences existing between the four
      anthocyanins detected in the two ecotypes, with those in the Tropea ecotype onion
      present at concentrations 20-230-fold higher than in the Montoro type onion. Both
      extracts reduced LDL oxidation about 6-fold and protected human erythrocytes from
      oxidative damage induced by HClO by about 40%. In addition, as a consequence of
      HClO treatment, glutathione concentration in erythrocytes was reduced about 50%
      and pretreatment with onion extracts induced a recovery of glutathione level by
      about 15-22%. Qualitative differences highlighted in the chemical composition of
      the two phenolic extracts, especially the total content of anthocyanins, which
      was 30-fold higher in Montoro type onion compared to Tropea ecotype, can be
      associated with the protective effects measured against oxidative damage induced
      in human erythrocytes. 

PMID- 25965972
TI  - Exciton Fine-Structure Splitting in Self-Assembled Lateral InAs/GaAs Quantum-Dot
      Molecular Structures.
AB  - Fine-structure splitting (FSS) of excitons in semiconductor nanostructures is a
      key parameter that has significant implications in photon entanglement and
      polarization conversion between electron spins and photons, relevant to quantum
      information technology and spintronics. Here, we investigate exciton FSS in self
      organized lateral InAs/GaAs quantum-dot molecular structures (QMSs) including
      laterally aligned double quantum dots (DQDs), quantum-dot clusters (QCs), and
      quantum rings (QRs), by employing polarization-resolved microphotoluminescence
      (MUPL) spectroscopy. We find a clear trend in FSS between the studied QMSs
      depending on their geometric arrangements, from a large FSS in the DQDs to a
      smaller FSS in the QCs and QRs. This trend is accompanied by a corresponding
      difference in the optical polarization directions of the excitons between these
      QMSs, namely, the bright-exciton lines are linearly polarized preferably along or
      perpendicular to the [110] crystallographic axis in the DQDs that also defines
      the alignment direction of the two constituting QDs, whereas in the QCs and QRs,
      the polarization directions are randomly oriented. We attribute the observed
      trend in the FSS to a significant reduction of the asymmetry in the lateral
      confinement potential of the excitons in the QRs and QCs as compared with the
      DQDs, as a result of a compensation between the effects of lateral shape
      anisotropy and piezoelectric field. Our work demonstrates that FSS strongly
      depends on the geometric arrangements of the QMSs, which effectively tune the
      degree of the compensation effects and are capable of reducing FSS even in a
      strained QD system to a limit similar to strain-free QDs. This approach provides
      a pathway in obtaining high-symmetry quantum emitters desirable for realizing
      photon entanglement and spintronic devices based on such nanostructures,
      utilizing an uninterrupted epitaxial growth procedure without special
      requirements for lattice-matched materials combinations, specific substrate
      orientations, and nanolithography. 

PMID- 25965973
TI  - Cellulose Acetate-Poly(N-isopropylacrylamide)-Based Functional Surfaces with
      Temperature-Triggered Switchable Wettability.
AB  - Temperature-triggered switchable nanofibrous membranes are successfully
      fabricated from a mixture of cellulose acetate (CA) and poly(N
      isopropylacrylamide) (PNIPAM) by employing a single-step direct electrospinning
      process. These hybrid CA-PNIPAM membranes demonstrate the ability to switch
      between two wetting states viz. superhydrophilic to highly hydrophobic states
      upon increasing the temperature. At room temperature (23  degrees C) CA-PNIPAM
      nanofibrous membranes exhibit superhydrophilicity, while at elevated temperature
      (40  degrees C) the membranes demonstrate hydrophobicity with a static water
      contact angle greater than 130 degrees . Furthermore, the results here
      demonstrate that the degree of hydrophobicity of the membranes can be controlled
      by adjusting the ratio of PNIPAM in the CA-PNIPAM mixture. 

PMID- 25965975
TI  - Dynamical Casimir effect in microwave cavities containing nonlinear crystals.
AB  - I consider a possibility of parametric amplification of the microwave vacuum
      field in a reentrant cavity enclosing a nonlinear crystal whose refractive index
      is modulated by periodic high-intensity short laser pulses. The main result is
      that the total number of created 'Casimir quanta' depends neither on the laser
      beam shape, nor on the duration or power of individual pulses, but it depends on
      the total energy of all the pulses, provided the duration of each pulse is much
      shorter than the period of field oscillations in the selected resonant mode. The
      scheme can be feasible if reliable materials with high nonlinear coefficients can
      be found. 

PMID- 25965974
TI  - Functional screening identifies MCT4 as a key regulator of breast cancer cell
      metabolism and survival.
AB  - Metabolic reprogramming in cancer enhances macromolecule biosynthesis and
      supports cell survival. Oncogenic drivers affect metabolism by altering distinct
      metabolic processes and render cancer cells sensitive to perturbations of the
      metabolic network. This study aimed to identify selective metabolic dependencies
      in breast cancer by investigating 17 breast cancer cells lines representative of
      the genetic diversity of the disease. Using a functional screen, we demonstrate
      here that monocarboxylate transporter 4 (MCT4) is an important regulator of
      breast cancer cell survival. MCT4 supports pH maintenance, lactate secretion and
      non-oxidative glucose metabolism in breast cancer cells. Moreover, MCT4 depletion
      caused an increased dependence of cancer cells on mitochondrial respiration and
      glutamine metabolism. MCT4 depletion reduced the ability of breast cancer cells
      to grow in a three-dimensional (3D) matrix or as multilayered spheroids.
      Moreover, MCT4 expression is regulated by the PI3K-Akt signalling pathway and
      highly expressed in HER2-positive breast cancers. These results suggest that MCT4
      is a potential therapeutic target in defined breast cancer subtypes and reveal
      novel avenues for combination treatment.

PMID- 25965976
TI  - Immobilization of alpha-amylase onto a calix[4]arene derivative: Evaluation of
      its enzymatic activity.
AB  - In order to enhance the cost-effectiveness practicability of enzymes in many
      industries such as pharmaceutical, food, medical and some other technological
      processes, there is great need to immobilize them onto a solid supports. In this
      study, a new and efficient immobilization of alpha-amylase from Saccharomyces
      cerevisiae has been developed by using the surface functionalization of
      calix[4]arene as support. A glutaraldehyde-containing amino group functionalized
      calix[4]arene was used to immobilize alpha-amylase covalently. In this procedure,
      imide bonds are formed between amino groups on the protein and aldehyde groups on
      the calix[4]arene surface. The surface modified support was characterized using
      Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy
      (SEM). The effect of various preparation conditions on the immobilized alpha
      amylase process such as immobilization time, enzyme concentration, temperature
      and pH were investigated. The influence of pH and temperature on the activity of
      free and immobilized alpha-amylase was also studied using starch as substrate.
      The optimum reaction temperature and pH value for the enzymatic conversion
      catalyzed by the immobilized alpha-amylase were 25 degrees C and 7, respectively.
      Compared to the free enzyme, the immobilized alpha-amylase retained 85% of its
      original activity and exhibited significant thermal stability than the free one
      and excellent durability. 

PMID- 25965977
TI  - Design and synthesis of newer potential 4-(N-acetylamino)phenol derived
      piperazine derivatives as potential cognition enhancers.
AB  - A series of novel hybrids has been designed, synthesized and evaluated for
      cognition enhancing activities through the inhibition of acetylcholinesterase
      (AChE) and by passive avoidance mouse model. All the compounds showed excellent
      AChE inhibition activities and potentially reversed the scopolamine induced
      memory deficit. Enzyme kinetic and molecular docking studies have confirmed their
      dual binding affinity and mixed type inhibition. Among them, compounds 1b and 2d
      displayed excellent IC50 values of 1.66MUM and 0.49MUM and competitive inhibitor
      constant Ki 43.66MUM and 4.10MUM respectively. Ex vivo study confirmed their CNS
      penetration and brain AChE inhibition abilities. Furthermore, 1b and 2d showed
      significant antiamnesic activity at a dose of 1.0mg/kg as compared to the
      reference compounds piracetam and rivastigmine. The results indicate that these
      two compounds emerged to be developed as cognition enhancers worthy of future
      pursuit. 

PMID- 25965978
TI  - RNA-Based Fluorescent Biosensors for Live Cell Imaging of Second Messenger Cyclic
      di-AMP.
AB  - Cyclic di-AMP (cdiA) is a second messenger predicted to be widespread in Gram
      positive bacteria, some Gram-negative bacteria, and Archaea. In the human
      pathogen Listeria monocytogenes, cdiA is an essential molecule that regulates
      metabolic function and cell wall homeostasis, and decreased levels of cdiA result
      in increased antibiotic susceptibility. We have generated fluorescent biosensors
      for cdiA through fusion of the Spinach2 aptamer to ligand-binding domains of cdiA
      riboswitches. The biosensor was used to visualize intracellular cdiA levels in
      live L. monocytogenes strains and to determine the catalytic domain of the
      phosphodiesterase PdeA. Furthermore, a flow cytometry assay based on this
      biosensor was used to screen for diadenylate cyclase activity and confirmed the
      enzymatic activity of DisA-like proteins from Clostridium difficile and
      Methanocaldococcus jannaschii. Thus, we have expanded the development of RNA
      based biosensors for in vivo metabolite imaging in Gram-positive bacteria and
      have validated the first dinucleotide cyclase from Archaea. 

PMID- 25965979
TI  - Characterising neural signatures of successful aging: Electrophysiological
      correlates of preserved episodic memory in older age.
AB  - While aging is associated with a gradual decline in memory, substantial
      preservation of function is observed in certain individuals and dissecting this
      heterogeneity is paramount to understanding successful aging. A cohort of elderly
      individuals were classified according to their level of memory preservation and
      administered a test of episodic memory in which participants were cued to learn
      or simply read each word and then to identify previously presented items in a
      delayed recognition phase. Mathematical modelling revealed that relatively
      preserved memory function was specifically linked to a faster rate of memorial
      evidence accumulation (drift rate). Analysis of event-related potentials at
      encoding revealed that high-performing elderly exhibited signals over parietal
      regions that discriminated between words to be learned vs. read for an additional
      300-ms compared to young subjects suggesting a compensatory encoding mechanism
      that was absent in the low-performing group. At recognition, parietal signals
      associated with recollection processes discriminated previously learned words
      from read words in the young and high-performing old but not in low-performing
      old. These results reveal that successful aging is associated with specific
      adaptive neural markers during both encoding and retrieval. 

PMID- 25965980
TI  - Synergistic effect of reductive and ligand-promoted dissolution of goethite.
AB  - Ligand-promoted dissolution and reductive dissolution of iron (hydr)oxide
      minerals control the bioavailability of iron in many environmental systems and
      have been recognized as biological iron acquisition strategies. This study
      investigated the potential synergism between ligands (desferrioxamine B (DFOB) or
      N,N'-Di(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid (HBED)) and a
      reductant (ascorbate) in goethite dissolution. Batch experiments were performed
      at pH 6 with ligand or reductant alone and in combination, and under both oxic
      and anoxic conditions. Goethite dissolution in the presence of reductant or
      ligand alone followed classic surface-controlled dissolution kinetics. Ascorbate
      alone does not promote goethite dissolution under oxic conditions due to rapid
      reoxidation of Fe(II). The rate coefficients for goethite dissolution by ligands
      are closely correlated with the stability constants of the aqueous Fe(III)-ligand
      complexes. A synergistic effect of DFOB and ascorbate on the rate of goethite
      dissolution was observed (total rates greater than the sum of the individual
      rates), and this effect was most pronounced under oxic conditions. For HBED,
      macroscopically the synergistic effect was hidden due to the inhibitory effect of
      ascorbate on HBED adsorption. After accounting for the concentrations of adsorbed
      ascorbate and HBED, a synergistic effect could still be identified. The potential
      synergism between ligand and reductant for iron (hydr)oxide dissolution may have
      important implications for iron bioavailability in soil environments.

PMID- 25965981
TI  - Decellularized cartilage may be a chondroinductive material for osteochondral
      tissue engineering.
AB  - Extracellular matrix (ECM)-based materials are attractive for regenerative
      medicine in their ability to potentially aid in stem cell recruitment,
      infiltration, and differentiation without added biological factors. In
      musculoskeletal tissue engineering, demineralized bone matrix is widely used, but
      recently cartilage matrix has been attracting attention as a potentially
      chondroinductive material. The aim of this study was thus to establish a chemical
      decellularization method for use with articular cartilage to quantify removal of
      cells and analyze the cartilage biochemical content at various stages during the
      decellularization process, which included a physically devitalization step. To
      study the cellular response to the cartilage matrix, rat bone marrow-derived
      mesenchymal stem cells (rBMSCs) were cultured in cell pellets containing cells
      only (control), chondrogenic differentiation medium (TGF-beta), chemically
      decellularized cartilage particles (DCC), or physically devitalized cartilage
      particles (DVC). The chemical decellularization process removed the vast majority
      of DNA and about half of the glycosaminoglycans (GAG) within the matrix, but had
      no significant effect on the amount of hydroxyproline. Most notably, the DCC
      group significantly outperformed TGF-beta in chondroinduction of rBMSCs, with
      collagen II gene expression an order of magnitude or more higher. While DVC did
      not exhibit a chondrogenic response to the extent that DCC did, DVC had a greater
      down regulation of collagen I, collagen X and Runx2. A new protocol has been
      introduced for cartilage devitalization and decellularization in the current
      study, with evidence of chondroinductivity. Such bioactivity along with providing
      the 'raw material' building blocks of regenerating cartilage may suggest a
      promising role for DCC in biomaterials that rely on recruiting endogenous cell
      recruitment and differentiation for cartilage regeneration. 

PMID- 25965982
TI  - Diagnostic value of nucleic acid amplification tests on bronchoalveolar lavage
      fluid for smear-negative pulmonary tuberculosis: a meta-analysis.
AB  - The diagnosis of smear-negative pulmonary tuberculosis (SNPT) remains a clinical
      challenge. Many studies suggest that nucleic acid amplification tests (NAATs) on
      bronchoalveolar lavage fluid (BALF) plays a role in diagnosing SNPT, but with
      considerable varying results. The current study aimed to summarize the overall
      diagnostic accuracy of NAATs assay on BALF for SNPT. A systematic literature
      search was performed and data were retrieved. Pooled sensitivity, specificity,
      positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic
      odds ratio (DOR) were calculated. A summary receiver operating characteristic
      curve and area under the curve (AUC) were used to evaluate the overall diagnostic
      performance. All the statistical analysis was performed by using STATA 12.0 and
      Meta-DiSc 1.4 software. A total of nine studies with 1214 subjects were included
      this meta-analysis. The pooled sensitivity, specificity, PLR, NLR and DOR were
      0.54 [95% CI (confidence interval): 0.48-0.59], 0.97 (95% CI: 0.95-0.98), 12.13
      (95% CI: 8.23-17.88), 0.36 (95% CI: 0.23-0.56) and 44.71 (95% CI: 22.30-89.63)
      respectively. The AUC was 0.96. Estimated positive and negative post-probability
      values for a SNPT prevalence of 20% were 82% and 7% respectively. No publication
      bias was identified. Current available evidence indicated that NAATs on BALF may
      play a role in diagnosing SNPT, whereas the results should be interpreted in
      parallel with clinical information of patients and the results of traditional
      tests. Further studies should be performed to confirm our findings. 

PMID- 25965983
TI  - Assessing both safe haven and secure base support in parent-child relationships.
AB  - Although the attachment construct refers to a child's tendency to use an
      attachment figure both as a safe haven in times of distress as well as a secure
      base from which to explore, approaches to assessing attachment at older ages have
      focused on safe haven behavior. We tested modified versions of the Friends and
      Family Interview and the Security Scale Questionnaire to examine separately the
      correlates of safe haven and secure base support from parents. The main study (n
      = 107 children, 10-14-year-olds) included both interview and questionnaire
      assessments of safe haven and secure base support from mothers and fathers. The
      two methods converged in expected ways, and both showed associations with
      narrative coherence. Children reported greater safe haven support from mothers
      and greater secure base support from fathers, suggesting secure base support is a
      key aspect of father-child attachment. Both mother-child and father-child
      relationships were related to children's school adjustment and coping. 

PMID- 25965984
TI  - Endoscopic findings in patients with eosinophilic esophagitis.
AB  - BACKGROUND: Endoscopy has a key role in establishing the diagnosis of
      eosinophilic esophagitis (EoE), but endoscopic features of EoE might not be well
      known. METHODS: All patients aged 18 or older who were diagnosed with EoE from
      2008 to 2013 were systematically identified retrospectively and findings at
      esophago-gastro-duodenoscopy (EGD) were reviewed by two experienced endoscopists
      through a query of the university hospital database. Patients in whom biopsies
      from the esophagus were lacking or inadequate for histopathological examination
      were excluded. RESULTS: 23 patients (17 male, 6 female) were included into the
      study (median age: 38 years, range: 19 to 71 years). Patients presented with the
      following symptoms: 12 (52 %) had bolus obstruction and 18 (78 %) dysphagia
      and/or chest pain. At EGD, 22 of 23 (96 %) patients were observed with at least
      one endoscopic feature of EoE, i. e., mucosal edema (52 %), longitudinal furrows
      (57 %), vertical furrows (48 %), or crepe paper esophagus (52 %). CONCLUSIONS:
      Typical endoscopic features were present in most patients in whom EoE was
      diagnosed. Recognizing typical characteristics of EoE is substantial for
      establishing the diagnosis and for taking biopsies.

PMID- 25965985
TI  - Percutaneous transhepatic cholangiography and drainage using extravascular
      contrast enhanced ultrasound.
AB  - BACKGROUND AND PURPOSE: Percutaneous transhepatic cholangiography and drainage
      (PTCD) is a common procedure for the diagnosis and treatment of benign and
      malignant biliary diseases. Ultrasound (US) is frequently used for the guidance
      of PTCD. Conventional fluoroscopy is applied to evaluate the biliary system, but
      delivers significant X-ray dosage to the patient and the interventional team. The
      purpose of this study is to test the ability of extravascular contrast-enhanced
      ultrasound (EV-CEUS) in US-guided PTCD to reduce or replace fluoroscopy. PATIENTS
      AND METHODS: 38 patients underwent PTCD. 2 - 4 mL doses of a SonoVue dilution
      were repeatedly injected to demonstrate correct needle and drainage positions in
      the biliary system and in the intestine during the intervention and during follow
      up to screen for complications. The results were compared to those of
      conventional radiography. RESULTS: The success rate for cholangiography was 100 %
      for EV-CEUS and fluoroscopy each. 27/38 patients (71 %) received a ring catheter,
      5/38 patients (13 %) received a metal stent. Only external drainage was possible
      in 6/38 patients (16 %) in the first session. In 50 % of them (3/38, 8 %)
      internalization was possible in the second attempt. With EV-CEUS the level of
      obstruction could be correctly diagnosed in 100 % of the patients. The degree of
      obstruction (complete/incomplete) could be correctly diagnosed in 37/38 patients
      (97 %). EV-CEUS was not able to demonstrate the guide wire. In 1/38 patient a
      hematoma appeared which was managed conservatively. Dislodgement was diagnosed in
      2/38 (5 %) patients during follow-up by injecting EV-CEUS solution into the
      drain. Pleural injury with fistula could be demonstrated in 1/38 (3 %) patients.
      CONCLUSION: EV-CEUS can monitor the success of insertion of needle and catheter,
      demonstrate or exclude complications, and therefore significantly reduce
      fluoroscopy time in US-guided PTCD. Fluoroscopy is needed whenever subtle wire
      steering is necessary as in most cases when the intestinal position of the drain
      is sought. If only external drainage is necessary fluoroscopy can be omitted.

PMID- 25965986
TI  - [Economic burden of Clostridium difficile enterocolitis in German hospitals based
      on routine DRG data].
AB  - BACKGROUND: Clostridium difficile associated diarrhea (CDAD) is not only a
      increasing medical but also economical problem. METHODS: Data from the DRG
      project group of the German society for digestive and metabolic diseases (DGVS)
      were analyzed for CDAD. Out of 430,875 cases from 37 German hospitals 2,767 cases
      were grouped by having CDAD either as primary (PD) or secondary diagnosis (SD;
      likely to be from a hospital source) in an initial or recurring hospital stay
      (RD). For comparison non-CDAD cases from the same hospitals from that year where
      matched using propensity score matching. As endpoints we defined LOS (length of
      stay), difference of LOS to national average LOS, total costs per case and
      difference between costs and revenue for all three groups. RESULTS: Patients from
      the PD group (n = 817) showed a mean LOS of 11.2 days compared to 8.5 days for
      the control group, 4,132 ? mean cost per case (536 ? more than control) and a
      mean loss of -1,064 ? per case compared to -636 ?. In the SD group (n = 1,840)
      patients stayed in the hospital for 28.8 days (control: 18.1 days), had costs of
      19,381 ? (control: 13,082 ?) and a loss of -3,442 ? compared to -849 ? in the
      control group. Recurring cases (RD; n = 110) showed a LOS of 37.3 days (control:
      21.3 days), had even higher costs (20.755 ? vs. 13,101 ?) and higher losses (
      4,196 ? vs. -1,109 ?). CONCLUSION: By extrapolating these findings CDAD not only
      harms patients but generates a yearly cost burden of 464 million ? for the German
      healthcare system including a loss of 197 million ? for German hospitals. To the
      authors' opinion sufficient measures against CDAD should include pre hospital
      risk reduction programs, introduction of effective therapeutic and hygienic
      strategies in hospitals as well as improvements in documentation for these cases
      to support further developments of the German DRG system.

PMID- 25965987
TI  - [Primary perivascular epitheloid cell tumour (PEComa) of the liver - is a new
      entity of the liver tumors?].
AB  - Perivascular epitheloid cell tumor (PEComa) is a rare tumor, characterized by
      dual Expression of smooth muscle and melanocytic markers. Due to the development
      of diagnostic procedures, we now diagnose PEComa more often. We report about a
      case of PEComa of the liver as an accidental finding. We analyze the clinical and
      morphological characteristics of this tumor and compare it with the data of the
      literature. Management of patients with PEComa is not yet standardized; therefore
      biopsy with immunhistochemical staining is necessary for the diagnosis. In case
      of liver tumors which cannot be classified by their morphology on imaging
      modalities, it is important to think about this rare entity.

PMID- 25965988
TI  - [Ultrasound in palliative care medicine].
AB  - This review summarizes ultrasound guided interventions in palliative care
      medicine. 

PMID- 25965989
TI  - [S2k-guideline gastrointestinal infectious diseases and Whipple's disease].

PMID- 25965990
TI  - Controlling defecation: to be (predator) or not to be (prey), that is the
      question...

PMID- 25965991
TI  - [Snack makes liver fat - how meal frequency does influence the development of
      NASH and obesity].

PMID- 25965992
TI  - Sequence-Dependent Solvation Dynamics of Minor-Groove Bound Ligand Inside Duplex
      DNA.
AB  - Ligand binding to minor-grooves of DNA depends on DNA-base sequence near its
      binding-site. However, it is not known how base-sequences affect the local
      solvation of ligand inside minor-grooves of DNA. Here we present a comprehensive
      study on sequence-dependent solvation dynamics of ligand inside duplex-DNA by
      measuring the static and dynamic fluorescence Stokes shifts of a popular groove
      binder, DAPI, inside DNA minor-grooves created by four different sequences; d(5'
      CGCGAATTCGCG-3')2, d(5'-CGCGTTAACGCG-3')2, d(5'-CGCGCAATTGCGCG-3')2, and d(5'
      CGCGCTTAAGCGCG-3')2, having different sequences near DAPI-binding site.
      Fluorescence up-conversion and time-correlated single photon counting techniques
      are employed to capture the dynamic Stokes shifts of DAPI over five decades in
      time from 100 fs to 10 ns. We show that the ligands sense different static and
      dynamic solvation inside minor-grooves created by different sequences: Only
      subtle change in the dynamics is seen in DNA containing -AATTG-, -TTAAG-, and 
      AATTC- sequences, which show power-law relaxation in initial time-decades,
      followed by biexponential decay in nanosecond time-scales. However, changing a
      single base (and the complementary base) near ligand-binding site from -TTAAG- to
      -TTAAC- drastically induces the dynamics to follow a single power-law relaxation
      over the entire five decades. The observed variation of dynamics possibly relate
      to the local DNA motions, coupled to the hydration dynamics near the ligand
      binding site. 

PMID- 25965994
TI  - Follicular necrotic keratinocytes - a helpful clue to the diagnosis of measles.
AB  - A skin specimen taken from the exanthem of a 22-year-old man with measles
      infection was examined by light microscopy. The most characteristic changes were
      foci of multiple necrotic keratinocytes, partially confluent and partially
      isolated, strictly within follicles and sebaceous glands. Serial sections
      revealed occasional necrotic and none-necrotic syncytial-type multinucleated
      epithelial cells in some infundibula. Neither nuclear nor cytoplasmic viral
      inclusions were present. 

PMID- 25965993
TI  - Dot1 histone methyltransferases share a distributive mechanism but have highly
      diverged catalytic properties.
AB  - The conserved histone methyltransferase Dot1 establishes an H3K79 methylation
      pattern consisting of mono-, di- and trimethylation states on histone H3 via a
      distributive mechanism. This mechanism has been shown to be important for the
      regulation of the different H3K79 methylation states in yeast. Dot1 enzymes in
      yeast, Trypanosoma brucei (TbDot1A and TbDot1B, which methylate H3K76) and human
      (hDot1L) generate very divergent methylation patterns. To understand how these
      species-specific methylation patterns are generated, the methylation output of
      the Dot1 enzymes was compared by expressing them in yeast at various expression
      levels. Computational simulations based on these data showed that the Dot1
      enzymes have highly distinct catalytic properties, but share a distributive
      mechanism. The mechanism of methylation and the distinct rate constants have
      implications for the regulation of H3K79/K76 methylation. A mathematical model of
      H3K76 methylation during the trypanosome cell cycle suggests that temporally
      regulated consecutive action of TbDot1A and TbDot1B is required for the observed
      regulation of H3K76 methylation states. 

PMID- 25965995
TI  - BMP-2 Is Involved in Scleral Remodeling in Myopia Development.
AB  - The development of myopia is associated with scleral remodeling, but it is
      unclear which factors regulate this process. This study investigated bone
      morphogenetic protein-2 (BMP-2) expression in the sclera of guinea pigs with lens
      induced myopia (LIM) and after recovery from myopia and evaluated the effect of
      BMP-2 on extracellular matrix (ECM) synthesis in human scleral fibroblasts (HSFs)
      cultured in vitro. Lens-induced myopia was brought about in two groups of guinea
      pigs (the lens-induced myopia and myopia recovery groups) by placing -4.00 D
      lenses on the right eye for three weeks. The left eye served as a contralateral
      control. In the recovery group, the lenses were removed after one week. The
      refractive power and axial length of the eyes were measured, and the BMP-2
      expression levels in the sclera were measured. After three weeks, the lens
      induced eyes acquired relative myopia in both groups of guinea pigs.
      Immunostaining of the eyeballs revealed significantly decreased BMP-2 expression
      in the posterior sclera of the myopic eyes compared to the contralateral eyes.
      One week after lens removal, BMP-2 expression recovered, and no differences were
      observed between the experimental and contralateral eyes in the recovery group.
      HSFs were cultured with BMP-2 or transforming growth factor-beta1 (TGF-beta1).
      Type I and type III collagen synthesis was significantly up-regulated following
      BMP-2 treatment in culture after one and two weeks, but the ratio of type III to
      type I collagen mRNA was not increased. Biosynthesis of glycosaminoglycan (GAG)
      and aggrecan was increased in HSFs treated with BMP-2. Some chondrogenesis
      associated genes expression increased in HSFs treated with BMP-2. From this
      study, we concluded that BMP-2 is involved in scleral remodeling in the
      development and recovery of lens-induced myopia. 

PMID- 25965997
TI  - Humour production may enhance observational learning of a new tool-use action in
      18-month-old infants.
AB  - Many studies have shown that making children laugh enhances certain cognitive
      capacities such as attention, motivation, perception and/or memory, which in turn
      enhance learning. However, no study thus far has investigated whether laughing
      has an effect on learning earlier in infancy. The goal of this study was to see
      whether using humour with young infants in a demonstration of a complex tool-use
      task can enhance their learning. Fifty-three 18-month-old infants participated in
      this study and were included either in a humorous or a control demonstration
      group. In both groups infants observed an adult using a tool to retrieve an out
      of-reach toy. What differed between groups was that in the humorous demonstration
      group, instead of playing with the toy, the adult threw it on the floor
      immediately after retrieval. The results show that infants who laughed at the
      demonstration in the humorous demonstration group reproduced significantly more
      frequent target actions than infants who did not laugh and those in the control
      group. This effect is discussed with regard to individual differences in terms of
      temperament and social capacities as well as positive emotion and dopamine
      release. 

PMID- 25965996
TI  - Recommendations for Accurate Resolution of Gene and Isoform Allele-Specific
      Expression in RNA-Seq Data.
AB  - Genetic variation modulates gene expression transcriptionally or post
      transcriptionally, and can profoundly alter an individual's phenotype. Measuring
      allelic differential expression at heterozygous loci within an individual, a
      phenomenon called allele-specific expression (ASE), can assist in identifying
      such factors. Massively parallel DNA and RNA sequencing and advances in
      bioinformatic methodologies provide an outstanding opportunity to measure ASE
      genome-wide. In this study, matched DNA and RNA sequencing, genotyping arrays and
      computationally phased haplotypes were integrated to comprehensively and
      conservatively quantify ASE in a single human brain and liver tissue sample. We
      describe a methodological evaluation and assessment of common bioinformatic steps
      for ASE quantification, and recommend a robust approach to accurately measure
      SNP, gene and isoform ASE through the use of personalized haplotype genome
      alignment, strict alignment quality control and intragenic SNP aggregation. Our
      results indicate that accurate ASE quantification requires careful bioinformatic
      analyses and is adversely affected by sample specific alignment confounders and
      random sampling even at moderate sequence depths. We identified multiple known
      and several novel ASE genes in liver, including WDR72, DSP and UBD, as well as
      genes that contained ASE SNPs with imbalance direction discordant with haplotype
      phase, explainable by annotated transcript structure, suggesting isoform derived
      ASE. The methods evaluated in this study will be of use to researchers performing
      highly conservative quantification of ASE, and the genes and isoforms identified
      as ASE of interest to researchers studying those loci. 

PMID- 25965998
TI  - Correction: Genetic Diversity and Differentiation of Juniperus thurifera in Spain
      and Morocco as Determined by SSR.

PMID- 25966000
TI  - Testing an egg yolk supplemented diet on boars to aid in sperm adaptation at 5
      degrees C.
AB  - In many species, extended semen can be stored at low temperatures to slow
      bacterial growth. However, boar semen performs poorly at temperatures below 15 
      degrees C and this poses unique challenges, as it is not easy to maintain a
      constant 15-19  degrees C during shipment. Some extenders have been formulated
      with egg yolk for storage at 5  degrees C but the addition of egg yolk is not
      applicable in the majority of commercial operations. The purpose of this study
      was to evaluate if boar dietary supplementation with powdered egg yolk imparts
      any protective effects on sperm quality when stored at 15  degrees C and 5 
      degrees C for up to 11 days in a conventional extender. Ten boars were fed a
      commercial diet with the addition of 0.11 Kg of powdered egg yolk for 10 weeks.
      Ejaculates collected on weeks 4, 6, 8, and 10 were processed for storage at both
      15  degrees C and 5  degrees C and compared with ejaculates from boars fed a
      standard diet. Throughout an 11-day storage period, sperm quality was assessed
      including several motility and morphologic parameters and select plasma membrane
      properties (fluidity, integrity, and triacylglycerol content). Linear regression
      models were used to describe effects of treatment, storage day, week and
      temperature on all sperm parameters. Overall, there were minimal beneficial
      effects of egg yolk treatment on sperm quality parameters. Sperm from egg yolk
      supplemented boars did have a slower decline in viability and plasma membrane
      fluidity than that observed in the control sperm when stored at 5  degrees C (p <
      0.001). Additionally, there was an increase in total morphologic abnormalities in
      sperm from egg yolk fed boars compared to controls at week 10 (p <  .001). In
      conclusion, the results of this study do not support a significant benefit to
      sperm quality or resistance to cold storage when feeding a 10-week dietary
      supplementation of 0.11 Kg powdered egg yolk to crossbred boars.

PMID- 25965999
TI  - Galpha12 overexpressed in hepatocellular carcinoma reduces microRNA-122
      expression via HNF4alpha inactivation, which causes c-Met induction.
AB  - MicroRNA-122 (miR-122) is implicated as a regulator of physiological and
      pathophysiological processes in the liver. Overexpression of Galpha12 is
      associated with overall survival in patients with hepatocellular carcinoma (HCC).
      Array-based miRNA profiling was performed on Huh7 stably transfected with
      activated Galpha12 to find miRNAs regulated by the Galpha12 pathway; among them,
      miR-122 was most greatly repressed. miR-122 directly inhibits c-Met expression,
      playing a role in HCC progression. Galpha12 destabilized HNF4alpha by
      accelerating ubiquitination, impeding constitutive expression of miR-122. miR-122
      mimic transfection diminished the ability of Galpha12 to increase c-Met and to
      activate ERK, STAT3, and Akt/mTOR, suppressing cell proliferation with augmented
      apoptosis. Consistently, miR-122 transfection prohibited tumor cell colony
      formation and endothelial tube formation. In a xenograft model, Galpha12
      knockdown attenuated c-Met expression by restoring HNF4alpha levels, and elicited
      tumor cell apoptosis but diminished Ki67 intensities. In human HCC samples,
      Galpha12 levels correlated to c-Met and were inversely associated with miR-122.
      Both miR-122 and c-Met expression significantly changed in tumor node metastasis
      (TNM) stage II/III tumors. Moreover, changes in Galpha12 and miR-122 levels
      discriminated recurrence-free and overall survival rates of HCC patients.
      Collectively, Galpha12 overexpression in HCC inhibits MIR122 transactivation by
      inactivating HNF4alpha, which causes c-Met induction, contributing to cancer
      aggressiveness. 

PMID- 25966001
TI  - Catalyst-controlled regiodivergent C-H borylation of multifunctionalized
      heteroarenes by using iridium complexes.
AB  - The regiodivergent C-H borylation of 2,5-disubstituted heteroarenes with
      bis(pinacolato)diboron was achieved by using iridium catalysts formed in situ
      from [Ir(OMe)(cod)]2 /dtbpy (cod=1,5-cyclooctadiene, dtbpy: 4,4'-di-tert-butyl
      2,2'-bipyridine) or [Ir(OMe)(cod)]2 /2 AsPh3 . When [Ir(OMe)(cod)]2 /dtbpy was
      used as the catalyst, borylation at the 4-position proceeded selectively to
      afford 4-borylated products in high yields (dtbpy system A). The regioselectivity
      changed when the [Ir(OMe)(cod)]2 /2 AsPh3 catalyst was used; 3-borylated products
      were obtained in high yields with high regioselectivity (AsPh3 system B). The
      regioselectivity of borylation was easily controlled by changing the ligands.
      This reaction was used in the syntheses of two different bioactive compound
      analogues by using the same starting material.

PMID- 25966002
TI  - [Not Available].

PMID- 25966003
TI  - Structure-Based Small Molecule Modulation of a Pre-Amyloid State: Pharmacological
      Enhancement of IAPP Membrane-Binding and Toxicity.
AB  - Islet amyloid polypeptide (IAPP) is a peptide hormone whose pathological self
      assembly is a hallmark of the progression of type II diabetes. IAPP-membrane
      interactions catalyze its higher-order self-assembly and also underlie its toxic
      effects toward cells. While there is great interest in developing small molecule
      reagents capable of altering the structure and behavior of oligomeric, membrane
      bound IAPP, the dynamic and heterogeneous nature of this ensemble makes it
      recalcitrant to traditional approaches. Here, we build on recent insights into
      the nature of membrane-bound states and develop a combined computational and
      experimental strategy to address this problem. The generalized structural
      approach efficiently identified diverse compounds from large commercial libraries
      with previously unrecognized activities toward the gain-of-function behaviors of
      IAPP. The use of appropriate computational prescreening reduced the experimental
      burden by orders of magnitude relative to unbiased high-throughput screening. We
      found that rationally targeting experimentally derived models of membrane-bound
      dimers identified several compounds that demonstrate the remarkable ability to
      enhance IAPP-membrane binding and one compound that enhances IAPP-mediated
      cytotoxicity. Taken together, these findings imply that membrane binding per se
      is insufficient to generate cytotoxicity; instead, enhanced sampling of rare
      states within the membrane-bound ensemble may potentiate IAPP's toxic effects. 

PMID- 25966004
TI  - Preanalytics: what can metabolomics learn from clinical chemistry?

PMID- 25966005
TI  - How can chromatographic baseline integration parameters be objectively
      established in the bioanalytical laboratory?

PMID- 25966006
TI  - Tiered approach to metabolite quantification: regional practices reviewed by
      Japan Bioanalysis Forum discussion group.

PMID- 25966007
TI  - Optimizing artificial neural network models for metabolomics and systems biology:
      an example using HPLC retention index data.
AB  - BACKGROUND: Artificial Neural Networks (ANN) are extensively used to model
      'omics' data. Different modeling methodologies and combinations of adjustable
      parameters influence model performance and complicate model optimization.
      METHODOLOGY: We evaluated optimization of four ANN modeling parameters (learning
      rate annealing, stopping criteria, data split method, network architecture) using
      retention index (RI) data for 390 compounds. Models were assessed by independent
      validation (I-Val) using newly measured RI values for 1492 compounds. CONCLUSION:
      The best model demonstrated an I-Val standard error of 55 RI units and was built
      using a Ward's clustering data split and a minimally nonlinear network
      architecture. Use of validation statistics for stopping and final model selection
      resulted in better independent validation performance than the use of test set
      statistics.

PMID- 25966008
TI  - Quantification of dabigatran and indirect quantification of dabigatran
      acylglucuronides in human plasma by LC-MS/MS.
AB  - BACKGROUND: An assay for the quantification of dabigatran and its active
      metabolites, dabigatran acylglucuronides, has not previously been described in
      detail. RESULTS: For the quantification of total dabigatran concentration (free
      dabigatran and acylglucuronides), samples were subjected to alkaline hydrolysis.
      For the quantification of free dabigatran, samples were acidified with ammonium
      formate. Following acetonitrile protein precipitation, the samples were analyzed
      by LC-MS/MS using gradient elution to ensure separation of dabigatran from
      dabigatran acylglucuronides. Mean recoveries >=98% were achieved. The assay was
      validated over the range 2.5-1000 ng/ml dabigatran, imprecision was <9% CV (<15%
      at LLOQ) and accuracy was 101-114%. CONCLUSION: An assay for dabigatran with
      indirect quantification of dabigatran acylglucuronides in plasma was developed,
      validated and applied.

PMID- 25966009
TI  - Simultaneous determination of centchroman and tamoxifen along with their
      metabolites in rat plasma using LC-MS/MS.
AB  - AIM: Tamoxifen and centchroman are two non-steroidal, selective estrogen
      receptors modulators, intended for long term therapy in the woman. Because of
      their wide spread use, there is a possibility of co-prescription of these agents.
      MATERIALS & METHODS: We studied the probable pharmacokinetic interaction between
      these agents in breast cancer model rats. A simple, sensitive and rapid LC-ESI
      MS/MS method was developed and validated for the simultaneous determination of
      tamoxifen, centchroman and their active metabolites. RESULTS: The method was
      linear over a range of 0.2-200 ng/ml. All validation parameters met the
      acceptance criteria according to regulatory guidelines. CONCLUSION: LC-MS/MS
      method for determination of tamoxifen, centchroman and their metabolites was
      developed and validated. Results show the potential of drug-drug interaction upon
      co-administration these two marketed drugs.

PMID- 25966010
TI  - The influence of sample collection methodology and sample preprocessing on the
      blood metabolic profile.
AB  - AIM: Blood serum and plasma have intrinsic differences in their composition and
      the preprocessing, such as clotting temperature in serum, and storage at room
      temperature may have further effect on metabolite concentrations. METHODS: The
      influence of sampling preprocessing on the metabolic profiles in serum and
      different types of plasma was investigated using liquid chromatography and
      comprehensive 2D gas chromatography coupled to a mass spectrometer. RESULTS: The
      profiles of polar metabolites were significantly dependent on the type of the
      sample, while lipid profiles were similar in serum and different types of plasma.
      Extended storage of plasma at room temperature resulted in degradation of lipids
      already after 1 day. Serum clotting at room temperature generally resulted in
      higher metabolite concentration compared with serum clotting on ice.

PMID- 25966011
TI  - Discovery of a novel trimebutine metabolite and its impact on N
      desmethyltrimebutine quantification by LC-MS/MS.
AB  - BACKGROUND: A failure in incurred sample reanalysis (ISR) for N
      desmethyltrimebutine (NDMT), during the analysis of a trimebutine-containing drug
      GIC-1001 Phase I study, led to the discovery of a never-before reported
      metabolite of trimebutine. RESULTS: A positive bias for NDMT during the ISR and
      post-reconstitution stability evaluations indicated the presence of an unstable
      metabolite of NDMT. Precursor ion scans performed on freshly extracted samples
      enabled the identification of this metabolite to be the NDMT glucuronide
      conjugate and its fragmentation pattern suggested that the glucuronide moiety was
      attached at the N-terminal of NDMT. CONCLUSIONS: An acidification step was
      introduced in the extraction procedure to completely hydrolyze the glucuronide
      and measure the total NDMT in plasma, rendering this method a successful fit-for
      purpose assay.

PMID- 25966012
TI  - Current and future bioanalytical approaches for stroke assessment.
AB  - Efforts are underway to develop novel platforms for stroke diagnosis to meet the
      criteria for effective treatment within the narrow time window mandated by the
      FDA-approved therapeutic (<3 h). Blood-based biomarkers could be used for rapid
      stroke diagnosis and coupled with new analytical tools, could serve as an
      attractive platform for managing stroke-related diseases. In this review, we will
      discuss the physiological processes associated with stroke and current diagnostic
      tools as well as their associated shortcomings. We will then review information
      on blood-based biomarkers and various detection technologies. In particular,
      point of care testing that permits small blood volumes required for the analysis
      and rapid turn-around time measurements of multiple markers will be presented. 

PMID- 25966014
TI  - Oligodendrocyte precursor cells synthesize neuromodulatory factors.
AB  - NG2 protein-expressing oligodendrocyte progenitor cells (OPC) are a persisting
      and major glial cell population in the adult mammalian brain. Direct synaptic
      innervation of OPC by neurons throughout the brain together with their ability to
      sense neuronal network activity raises the question of additional physiological
      roles of OPC, supplementary to generating myelinating oligodendrocytes. In this
      study we investigated whether OPC express neuromodulatory factors, typically
      synthesized by other CNS cell types. Our results show that OPC express two well
      characterized neuromodulatory proteins: Prostaglandin D2 synthase (PTGDS) and
      neuronal Pentraxin 2 (Nptx2/Narp). Expression levels of the enzyme PTGDS are
      influenced in cultured OPC by the NG2 intracellular region which can be released
      by cleavage and localizes to glial nuclei upon transfection. Furthermore PTGDS
      mRNA levels are reduced in OPC from NG2-KO mouse brain compared to WT cells after
      isolation by cell sorting and direct analysis. These results show that OPC can
      contribute to the expression of these proteins within the CNS and suggest PTGDS
      expression as a downstream target of NG2 signaling. 

PMID- 25966013
TI  - Alternative matrices for therapeutic drug monitoring of immunosuppressive agents
      using LC-MS/MS.
AB  - Immunosuppressive drugs used in solid organ transplants typically have narrow
      therapeutic windows and high intra- and intersubject variability. To ensure
      satisfactory exposure, therapeutic drug monitoring (TDM) plays a pivotal role in
      any successful posttransplant maintenance therapy. Currently, recommendations for
      optimum immunosuppressant concentrations are based on blood/plasma measurements.
      However, they introduce many disadvantages, including poor prediction of
      allograft survival and toxicity, a weak correlation with drug concentrations at
      the site of action and the invasive nature of the sample collection. Thus,
      alternative matrices have been investigated. This paper reviews tandem-mass
      spectrometry (LC-MS/MS) methods used for the quantification of immunosuppressant
      drugs utilizing nonconventional matrices, namely oral fluids, fingerprick blood
      and intracellular and intratissue sampling. The advantages, disadvantages and
      clinical application of such alternative mediums are discussed. Additionally,
      sample extraction techniques and basic chromatography information regarding these
      methods are presented in tabulated form. 

PMID- 25966015
TI  - Use of electronic health records to ascertain, validate and phenotype acute
      myocardial infarction: A systematic review and recommendations.
AB  - Electronic health records (EHRs) offer the opportunity to ascertain clinical
      outcomes at large scale and low cost, thus facilitating cohort studies, quality
      of care research and clinical trials. For acute myocardial infarction (AMI) the
      extent to which different EHR sources are accessible and accurate remains
      uncertain. Using MEDLINE and EMBASE we identified thirty three studies, reporting
      a total of 128658 patients, published between January 2000 and July 2014 that
      permitted assessment of the validity of AMI diagnosis drawn from EHR sources
      against a reference such as manual chart review. In contrast to clinical
      practice, only one study used EHR-derived markers of myocardial necrosis to
      identify possible AMI cases, none used electrocardiogram findings and one used
      symptoms in the form of free text combined with coded diagnosis. The remaining
      studies relied mostly on coded diagnosis. Thirty one studies reported positive
      predictive value (PPV)>= 70% between AMI diagnosis from both secondary care and
      primary care EHRs and the reference. Among fifteen studies reporting EHR-derived
      AMI phenotypes, three cross-referenced ST-segment elevation AMI diagnosis (PPV
      range 71-100%), two non-ST-segment elevation AMI (PPV 91.0, 92.1%), three non
      fatal AMI (PPV range 82-92.2%) and six fatal AMI (PPV range 64-91.7%). Clinical
      coding of EHR-derived AMI diagnosis in primary care and secondary care was found
      to be accurate in different clinical settings and for different phenotypes.
      However, markers of myocardial necrosis, ECG and symptoms, the cornerstones of a
      clinical diagnosis, are underutilised and remain a challenge to retrieve from
      EHRs.

PMID- 25966016
TI  - Beneficial Effects of Positive Airway Pressure Therapy for Sleep-Disordered
      Breathing in Heart Failure Patients With Preserved Left Ventricular Ejection
      Fraction.
AB  - BACKGROUND: Right-heart dysfunction is associated with poor prognosis in heart
      failure with preserved left ventricular ejection fraction (HFpEF). It remains
      unclear whether sleep-disordered breathing (SDB) treatment using positive airway
      pressure (PAP) improves right-heart and pulmonary function and exercise capacity
      and reduces mortality rates of HFpEF patients. HYPOTHESIS: PAP may improve right
      heart and pulmonary function, exercise capacity and prognosis in HFpEF patients
      with SDB. METHODS: One hundred nine consecutive patients with HFpEF (left
      ventricular ejection fraction >50%) and moderate to severe SDB (apnea-hypopnea
      index >=15/h) treated with medications were divided into 2 groups: 31 patients
      with PAP (PAP group) and 78 patients without PAP (non-PAP group). Right
      ventricular fractional area change (RV-FAC), tricuspid valve regurgitation
      pressure gradient (TR-PG), tricuspid valve E/E', forced expiratory volume in 1
      second/forced vital capacity (FEV1 /FVC), percentage of vital capacity, and peak
      VO2 were determined before and 6 months later, and all-cause mortality was
      followed up for 916 days. RESULTS: All parameters improved in the PAP group (RV
      FAC, 36.0% -46.5%; TR-PG, 31.1 mm Hg-22.4 mm Hg; tricuspid valve E/E', 7.8-5.1;
      FEV1 /FVC, 83.9%-89.8%; percentage of vital capacity, 83.5%-89.9%; and peak VO2 ,
      16.6 mL/kg/min-19.6 mL/kg/min; P <0.05, respectively) but not in the non-PAP
      group. Importantly, all-cause mortality was significantly lower in the PAP group
      than in the non-PAP group (0% vs 12.8%; log-rank P = 0.014). CONCLUSIONS:
      Positive airway pressure improves right-heart and pulmonary function and exercise
      capacity and may reduce all-cause mortality in patients with HFpEF and SDB.

PMID- 25966017
TI  - Memcomputing with membrane memcapacitive systems.
AB  - We show theoretically that networks of membrane memcapacitive systems-capacitors
      with memory made out of membrane materials-can be used to perform a complete set
      of logic gates in a massively parallel way by simply changing the external input
      amplitudes, but not the topology of the network. This polymorphism is an
      important characteristic of memcomputing (computing with memories) that closely
      reproduces one of the main features of the brain. A practical realization of
      these membrane memcapacitive systems, using, e.g., graphene or other 2D
      materials, would be a step forward towards a solid-state realization of
      memcomputing with passive devices. 

PMID- 25966018
TI  - Polymer immobilized Cu(I) formation and azide-alkyne cycloaddition: A one pot
      reaction.
AB  - During the polymerization of aniline using copper sulphate, act as an oxidizing
      agent, the in-situ synthesized Cu(I) ion catalyzed the cyclo-addition between
      azides and alkynes. This work represents the merging of two steps, synthesis of
      the catalyst and application of the catalyst, in a one pot reaction. The
      elimination of the separate catalyst synthesis step is economic in terms of cost
      and time. As aniline was used as one of the reactant components so there is no
      requirement to use additional base for this reaction that further eliminates the
      cost of the process. Again, the catalyst can be readily recovered by filtration
      and efficiently used for the several sets of reactions without any significant
      loss of catalytic activity. 

PMID- 25966019
TI  - Voltage-Controlled Ring Oscillators Based on Inkjet Printed Carbon Nanotubes and
      Zinc Tin Oxide.
AB  - A voltage-controlled ring oscillator is implemented with double-gate
      complementary transistors where both the n- and p-channel semiconductors are
      deposited by inkjet printing. Top gates added to transistors in conventional ring
      oscillator circuits control not only threshold voltages of the constituent
      transistors but also the oscillation frequencies of the ring oscillators. The
      oscillation frequency increases or decreases linearly with applied top gate
      potential. The field-effect transistor materials system that yields such linear
      behavior has not been previously reported. In this work, we demonstrate details
      of a material system (gate insulator, p- and n-channel semiconductors) that
      results in very linear frequency changes with control gate potential. Our use of
      a double layer top dielectric consisting of a combination of solution processed
      P(VDF-TrFE) and Al2O3 deposited by atomic layer deposition leads to low operating
      voltages and near-optimal device characteristics from a circuit standpoint. Such
      functional blocks will enable the realization of printed voltage-controlled
      oscillator-based analog-to-digital converters. 

PMID- 25966020
TI  - Erratum: Genomic signatures of human and animal disease in the zoonotic pathogen
      Streptococcus suis.

PMID- 25966021
TI  - Volumetric hand-held optoacoustic angiography as a tool for real-time screening
      of dense breast.
AB  - Existing mammographic screening solutions are generally associated with several
      major drawbacks, such as exposure to ionizing radiation or insufficient
      sensitivity in younger populations with radiographically-dense breast. Even when
      combined with ultrasound or magnetic resonance imaging, X-Ray mammography may
      still attain unspecific or false positive results. Thus, development of new
      breast imaging tools represents a timely medical challenge. We report on a new
      approach to high-resolution functional and anatomical breast angiography using
      volumetric hand-held optoacoustic tomography, which employs light intensities
      safe for human use. Experiments in young healthy volunteers with fibroglandular
      dominated dense breasts revealed the feasibility of rendering three-dimensional
      images representing vascular anatomy and functional blood oxygenation parameters
      at video rate. Sufficient contrast was achieved at depths beyond 2 cm within
      dense breasts without compromising the real-time imaging performance. The
      suggested solution may thus find applicability as a standalone or supplemental
      screening tool for early detection and follow-up of carcinomas in
      radiographically-dense breasts. Volumetric handheld optoacoustic tomography
      scanner uses safe pulses of near-infrared light to render three-dimensional
      images of deep vascular anatomy, blood oxygenation and breast parenchyma at video
      rate.

PMID- 25966022
TI  - Inclusion bodies and pH lowering: as an effect of gold nanoparticles in
      Streptococcus pneumoniae.
AB  - Streptococcus pneumoniae is a human pathogen whose principal virulence factor is
      its capsule. This structure allows the bacterium to evade the human immune
      system. Treatment of infections caused by this bacterium is based on antibiotics;
      however, the emergence of antibiotic-resistant strains makes this task
      increasingly difficult. Therefore, it is necessary to investigate new therapies,
      such as those based on gold nanoparticles, for which unfortunately the mechanisms
      involved have not yet been investigated. As far as we know, this study is the
      first that attempts to explain how gold nanoparticles destroy the bacterium
      Streptococcus pneumoniae. We found that the mean particle size was an important
      issue, and that the effect on the bacterium was dose-dependent. Cellular growth
      was inhibited by the presence of the nanoparticles, as was cell viability. The pH
      of the bacterial growth media was acidified, but interestingly the reactive
      species were not affected. A transmission electron microscopy analysis revealed
      the presence of inclusion bodies of gold nanoparticles within the bacterium. We
      present the first findings that attempt to explain how gold nanoparticles lyse
      Gram-positive bacteria. 

PMID- 25966023
TI  - Hydrothermal-acid treatment for effectual extraction of eicosapentaenoic acid
      (EPA)-abundant lipids from Nannochloropsis salina.
AB  - Hydrothermal acid treatment, was adopted to extract eicosapentaenoic acid (EPA)
      from wet biomass of Nannochloropsis salina. It was found that sulfuric acid-based
      treatment increased EPA yield from 11.8 to 58.1 mg/g cell in a way that was
      nearly proportional to its concentration. Nitric acid exhibited the same pattern
      at low concentrations, but unlike sulfuric acid its effectiveness unexpectedly
      dropped from 0.5% to 2.0%. The optimal and minimal conditions for hydrothermal
      acid pretreatment were determined using a statistical approach; its maximum EPA
      yield (predicted: 43.69 mg/g cell; experimental: 43.93 mg/g cell) was established
      at a condition of 1.27% of sulfuric acid, 113.34  degrees C of temperature, and
      36.71 min of reaction time. Our work demonstrated that the acid-catalyzed cell
      disruption, accompanied by heat, can be one potentially promising option for
      omega-3 fatty acids extraction.

PMID- 25966024
TI  - Development of a Validated LC Method for Separation of Process-Related Impurities
      Including the R-Enantiomer of S-Pramipexole on Polysaccharide Chiral Stationary
      Phases.
AB  - Despite the availability of a few methods for individual separation of S
      pramipexole from its process-related impurities, no common liquid chromatography
      (LC) method is reported so far in the literature. The present article describes
      the development of a single-run LC method for simultaneous determination of S
      pramipexole and its enantiomeric and process-related impurities on a Chiralpak AD
      H (150 x 4.6 mm, 5MUm) column using n-hexane/ethanol/n-butylamine (75:25:0.1
      v/v/v) as a mobile phase in an isocratic mode of elution at a flow rate of 1.2
      ml/min at 30 degrees C. The chromatographic eluents were monitored at a
      wavelength of 260 nm using a photodiode array detector. Excellent
      enantioseparation with good resolutions (Rs >= 2.88) and peak shapes (As <= 1.21)
      for all analytes was achieved. The proposed method was validated according to
      International Conference Harmonization (ICH) guidelines in terms of accuracy,
      precision, sensitivity, and linearity. Limits of quantification of impurities
      (0.25-0.55 MUg/ml) indicate the highest sensitivity achievable by the proposed
      method. The method has an advantage of selectivity and suitability for routine
      determination of not only chiral impurity but also all possible related
      substances in active pharmaceutical ingredients of S-pramipexole.

PMID- 25966026
TI  - Enhancement of early cervical cancer diagnosis with epithelial layer analysis of
      fluorescence lifetime images.
AB  - This work reports the use of layer analysis to aid the fluorescence lifetime
      diagnosis of cervical intraepithelial neoplasia (CIN) from H&E stained cervical
      tissue sections. The mean and standard deviation of lifetimes in single region of
      interest (ROI) of cervical epithelium were previously shown to correlate to the
      gold standard histopathological classification of early cervical cancer. These
      previously defined single ROIs were evenly divided into layers for analysis. A 10
      layer model revealed a steady increase in fluorescence lifetime from the inner to
      the outer epithelial layers of healthy tissue sections, suggesting a close
      association with cellular maturity. The shorter lifetime and minimal lifetime
      increase towards the epithelial surface of CIN-affected regions are in good
      agreement with the absence of cellular maturation in CIN. Mean layer lifetimes in
      the top-half cervical epithelium were used as feature vectors for extreme
      learning machine (ELM) classifier discriminations. It was found that the proposed
      layer analysis technique greatly improves the sensitivity and specificity to
      94.6% and 84.3%, respectively, which can better supplement the traditional gold
      standard cervical histopathological examinations. 

PMID- 25966027
TI  - Ciliates from ancient permafrost: Assessment of cold resistance of the resting
      cysts.
AB  - There is evidence that resting cysts of soil ciliates and numerous taxa of other
      protists can survive in permafrost for thousands of years at subzero
      temperatures; however, our knowledge about mechanisms of long term cryobiosis
      remains incomplete. In order to better understand the means by which ancient
      cysts survive, we investigated resistance to cyclical supercooling stress of
      resting cysts of the soil ciliate Colpoda steinii (Colpodida, Ciliophora). Three
      clonal strains were used for comparison, isolated from Siberian tundra soil,
      ancient Holocene (5-7,000 y) and late Pleistocene (32-35,000 y) permafrost
      sediments. To determine the viability of the ancient and contemporary ciliate
      cysts we improved and validated a cultivation-independent method of vital
      fluorescent staining with a combination of two nucleic acid binding dyes,
      acridine orange and propidium iodide. The viability of Colpoda steinii cysts
      during low-temperature experiments was measured using both the proposed vital
      fluorescent staining method and standard germination test. Our results indicate
      that the dual-fluorescence technique is a more accurate, rapid, and efficient
      method for estimating cyst viability. We found that cysts of ancient ciliates
      display lower tolerance to the impact of cyclical cold compared to cysts of
      contemporary ciliates from Siberian permafrost affected soils. 

PMID- 25966025
TI  - Clinical and histopathological features of patients with systemic sclerosis
      undergoing endomyocardial biopsy.
AB  - BACKGROUND: Cardiac involvement in systemic sclerosis (SSc) is associated with a
      variable phenotype including heart failure, arrhythmias and pulmonary
      hypertension. The aim of the present study was to evaluate clinical
      characteristics, histopathological findings and outcome of patients with SSc and
      a clinical phenotype suggesting cardiac involvement. METHODS AND RESULTS: 25
      patients with SSc and clinical signs of cardiac involvement were included between
      June 2007 and December 2010. They underwent routine clinical work-up including
      laboratory testing, echocardiography, left and right heart catheterization,
      holter recordings and endomyocardial biopsy. Primary endpoint (EP) was defined as
      the combination of cardiovascular death, arrhythmic endpoints (defined as
      appropriate discharge of implantable cardioverter defibrillator (ICD)) or
      rehospitalization due to heart failure. The majority of patients presented with
      slightly impaired left ventricular function (mean LVEF 54.1+/-9.0%, determined by
      echocardiography). Endomyocardial biopsies detected cardiac fibrosis in all
      patients with a variable area percentage of 8% to 32%. Cardiac inflammation was
      diagnosed as follows: No inflammation in 3.8%, isolated inflammatory cells in
      38.5%, a few foci of inflammation in 30.8%, several foci of inflammation in
      15.4%, and pronounced inflammation in 7.7% of patients. During follow up (FU)
      (22.5 months), seven (28%) patients reached the primary EP. Patients with
      subsequent events showed a higher degree of fibrosis and inflammation in the
      myocardium by trend. While patients with an inflammation grade 0 or 1 showed an
      event rate of 18.2%, the subgroup of patients with an inflammation grade 2
      presented with an event rate of 25% versus an event rate of 50% in the subgroup
      of patients with an inflammation grade 3 and 4, respectively (p=0.193).
      Furthermore, the subgroup of patients with fibrosis grade 1 showed an event rate
      of 11%, patients with fibrosis grade 2 and 3 presented with an event rate of 33%
      and 42% respectively (p = 0.160). CONCLUSIONS: Patients with SSc and clinical
      signs of cardiac involvement presented with mildly impaired LVEF. Prognosis was
      poor with an event rate of 28% within 22.5 months FU and was associated with the
      degree of cardiac inflammation and fibrosis.

PMID- 25966028
TI  - No difference in the incidence of malaria in human-landing mosquito catch
      collectors and non-collectors in a Senegalese village with endemic malaria.
AB  - BACKGROUND: The human landing catches is the gold standard method used to study
      the vectors of malaria and to estimate their aggressiveness. However, this method
      has raised safety concerns due to a possible increased risk of malaria or other
      mosquito-borne diseases among the mosquito collectors. The aim of this study was
      to evaluate the incidence of malaria attacks among mosquito collectors and to
      compare these results with those of non-collectors in a Senegalese village.
      METHODS: From July 1990 to December 2011, a longitudinal malaria study involving
      mosquito collectors and non-collectors was performed in Dielmo village, Senegal.
      During the study period, 4 drugs were successively used to treat clinical
      malaria, and long-lasting insecticide-treated nets were offered to all villagers
      in July 2008. No malaria chemoprophylaxis was given to mosquito collectors.
      Incidence of uncomplicated clinical malaria and asymptomatic malaria infection
      were analyzed among these two groups while controlling for confounding factors
      associated with malaria risk in random effects negative binomial and logistic
      regression models, respectively. RESULTS: A total of 3,812 person-trimester
      observations of 199 adults at least 15 years of age were analyzed. Clinical
      malaria attacks accounted for 6.3% both in collectors and non-collectors, and
      asymptomatic malaria infections accounted for 21% and 20% in collectors and non
      collectors, respectively. A non-significant lower risk of malaria was observed in
      the collector group in comparison with the non-collector group after adjusting
      for other risk factors of malaria and endemicity level (Clinical malaria:
      adjusted incidence rate ratio = 0.89; 95% confidence interval = 0.65-1.22; p=
      0.47). CONCLUSION: Being a mosquito collector in Dielmo was not significantly
      associated with an increased risk of malaria both under holoendemic, mesoendemic
      and hypoendemic conditions of malaria epidemiology. This result supports the view
      that HLC, the most accurate method for evaluating malaria transmission, may be
      used without health concerns in Dielmo.

PMID- 25966029
TI  - Metal-free N-arylation of secondary amides at room temperature.
AB  - The arylation of secondary acyclic amides has been achieved with diaryliodonium
      salts under mild and metal-free conditions. The methodology has a wide scope,
      allows synthesis of tertiary amides with highly congested aryl moieties, and
      avoids the regioselectivity problems observed in reactions with
      (diacetoxyiodo)benzene. 

PMID- 25966031
TI  - Diaminodiacid-based solid-phase synthesis of all-hydrocarbon stapled alpha
      helical peptides.
AB  - An alternative stapling strategy is described herein using Fmoc-solid phase
      peptide synthesis (SPPS) that employed pre-prepared diaminodiacid building blocks
      to introduce all-hydrocarbon staples into peptides by on-resin cyclization.
      Compared to unstapled native peptides, diaminodiacid-based stapled peptides
      exhibited an increased alpha-helicity ratio and stability toward protease.
      Moreover, the linkage length was found to affect the bioactivity of the peptides
      and their ability to inhibit the Wnt pathway. Therefore, the new stapling method
      provides an alternative way to obtain stapled peptides with tunable linkers of
      diaminodiacids. 

PMID- 25966030
TI  - alpha-Tocopherol supplementation reduces 5-nitro-gamma-tocopherol accumulation by
      decreasing gamma-tocopherol in young adult smokers.
AB  - gamma-Tocopherol (gamma-T) scavenges reactive nitrogen species (RNS) to form 5
      NO2-gamma-T (NGT). However, alpha-T supplementation decreases circulating gamma
      T, which could limit its RNS scavenging activities. We hypothesized that alpha-T
      supplementation would mitigate NGT accumulation by impairing gamma-T status.
      Healthy smokers (21 +/- 1 y, n = 11) and non-smokers (21 +/- 2 y, n = 10)
      ingested 75 mg/d each of RRR- and all-rac-alpha-tocopheryl acetate for 6 d.
      Plasma alpha-T, gamma-T, gamma-carboxyethyl hydroxychromanol (CEHC), NGT, and
      nitrate/nitrite were measured prior to supplementation (Pre), the morning after 6
      consecutive evenings of supplementation (Post 1), and on the mornings of d 6
      (Post 6) and d 14 (Post 14) during the post-supplementation period. alpha-T
      supplementation increased plasma alpha-T, and decreased gamma-T, in both groups
      and these returned to Pre concentrations on Post 6 regardless of smoking status.
      Plasma gamma-CEHC increased after the first dose of supplementation in both
      groups, suggesting that alpha-T supplementation decreased plasma gamma-T in part
      by increasing its metabolism. Plasma NGT and nitrate/nitrite concentrations at
      Pre were greater in smokers, indicating greater nitrative stress due to cigarette
      smoking. Plasma NGT concentration was lowered only in smokers on Post 1 and Post
      6 and was restored to Pre levels on Post 14. Plasma nitrate/nitrite tended (P =
      0.07) to increase post-supplementation only in smokers, supporting decreases in
      RNS scavenging by gamma-T. Plasma NGT concentration was more strongly correlated
      (P < 0.05) with gamma-T in smokers (R = 0.83) compared with non-smokers (R =
      0.50), supporting that alpha-T-mediated decreases in gamma-T reduces NGT
      formation. These data indicate that alpha-T supplementation limits gamma-T
      scavenging of RNS in smokers by decreasing gamma-T availability. 

PMID- 25966032
TI  - Virological characterization of influenza H1N1pdm09 in Vietnam, 2010-2013.
AB  - OBJECTIVES: Influenza A/H1N1pdm09 virus was first detected in Vietnam on May 31,
      2009, and continues to circulate in Vietnam as a seasonal influenza virus. This
      study has monitored genotypic and phenotypic changes in this group of viruses
      during 2010-2013 period. DESIGN AND SETTING: We sequenced hemagglutinin (HA) and
      neuraminidase (NA) genes from representative influenza A/H1N1pdm09 and compared
      with vaccine strain A/California/07/09 and other contemporary isolates from
      neighboring countries. Hemagglutination inhibition (HI) and neuraminidase
      inhibition (NAI) assays also were performed on these isolates. SAMPLE:
      Representative influenza A/H1N1pdm09 isolates (n = 61) from ILI and SARI
      surveillances in northern Vietnam between 2010 and 2013. MAIN OUTCOME MEASURES
      AND RESULTS: The HA and NA phylogenies revealed six and seven groups,
      respectively. Five isolates (8.2%) had substitutions G155E and N156K in the HA,
      which were associated with reduced HI titers by antiserum raised against the
      vaccine virus A/California/07/2009. One isolate from 2011 and one isolate from
      2013 had a predicted H275Y substitution in the neuraminidase molecule, which was
      associated with reduced susceptibility to oseltamivir in a NAI assay. We also
      identified a D222N change in the HA of a virus isolated from a fatal case in
      2013. CONCLUSIONS: Significant genotypic and phenotypic changes in A/ H1N1pdm09
      influenza viruses were detected by the National Influenza Surveillance System
      (NISS) in Vietnam between 2010 and 2013 highlighting the value of this system to
      Vietnam and to the region. Sustained NISS and continued virological monitoring of
      seasonal influenza viruses are required for vaccine policy development in
      Vietnam. 3.

PMID- 25966033
TI  - Classification of neurological abnormalities in children with congenital
      melanocytic naevus syndrome identifies magnetic resonance imaging as the best
      predictor of clinical outcome.
AB  - BACKGROUND: The spectrum of central nervous system (CNS) abnormalities described
      in association with congenital melanocytic naevi (CMN) includes congenital,
      acquired, melanotic and nonmelanotic pathology. Historically, symptomatic CNS
      abnormalities were considered to carry a poor prognosis, although studies from
      large centres have suggested a much wider variation in outcome. OBJECTIVES: To
      establish whether routine MRI of the CNS is a clinically relevant investigation
      in children with multiple CMN (more than one at birth), and to subclassify
      radiological abnormalities. METHODS: Of 376 patients seen between 1991 and 2013,
      289 fulfilled our criterion for a single screening CNS MRI, which since 2008 has
      been more than one CMN at birth, independent of size and site of the largest
      naevus. Cutaneous phenotyping and radiological variables were combined in a
      multiple regression model of long-term outcome measures (abnormal
      neurodevelopment, seizures, requirement for neurosurgery). RESULTS: Twenty-one
      per cent of children with multiple CMN had an abnormal MRI. Abnormal MRI was the
      most significant predictor of all outcome measures. Abnormalities were
      subclassified into group 1 'intraparenchymal melanosis alone' (n = 28) and group
      2 'all other pathology' (n = 18). Group 1 was not associated with malignancy or
      death during the study period, even when symptomatic with seizures or
      developmental delay, whereas group 2 showed a much more complex picture,
      requiring individual assessment. CONCLUSIONS: For screening for congenital
      neurological lesions a single MRI in multiple CMN is a clinically relevant
      strategy. Any child with a stepwise change in neurological/developmental symptoms
      or signs should have an MRI with contrast of the brain and spine to look for new
      CNS melanoma.

PMID- 25966035
TI  - Reducing bacterial contamination in fuel ethanol fermentations by ozone treatment
      of uncooked corn mash.
AB  - Ozonation of uncooked corn mash from the POET BPX process was investigated as a
      potential disinfection method for reducing bacterial contamination prior to
      ethanol fermentation. Corn mash (200 g) was prepared from POET ground corn and
      POET corn slurry and was ozonated in 250 mL polypropylene bottles. Lactic and
      acetic acid levels were monitored daily during the fermentation of ozonated,
      aerated, and nontreated corn mash samples to evaluate bacterial activity.
      Glycerol and ethanol contents of fermentation samples were checked daily to
      assess yeast activity. No yeast supplementation, no addition of other
      antimicrobial agents (such as antibiotics), and spiking with a common lactic acid
      bacterium found in corn ethanol plants, Lactobacillus plantarum, amplified the
      treatment effects. The laboratory-scale ozone dosages ranged from 26-188 mg/L,
      with very low estimated costs of $0.0008-0.006/gal ($0.21-1.6/m(3)) of ethanol.
      Ozonation was found to decrease the initial pH of ground corn mash samples, which
      could reduce the sulfuric acid required to adjust the pH prior to ethanol
      fermentation. Lactic and acetic acid levels tended to be lower for samples
      subjected to increasing ozone dosages, indicating less bacterial activity. The
      lower ozone dosages in the range applied achieved higher ethanol yields.
      Preliminary experiments on ozonating POET corn slurry at low ozone dosages were
      not as effective as using POET ground corn, possibly because corn slurry samples
      contained recycled antimicrobials from the backset. The data suggest additional
      dissolved and suspended organic materials from the backset consumed the ozone or
      shielded the bacteria. 

PMID- 25966034
TI  - Probe Region Expression Estimation for RNA-Seq Data for Improved Microarray
      Comparability.
AB  - Rapidly growing public gene expression databases contain a wealth of data for
      building an unprecedentedly detailed picture of human biology and disease. This
      data comes from many diverse measurement platforms that make integrating it all
      difficult. Although RNA-sequencing (RNA-seq) is attracting the most attention, at
      present, the rate of new microarray studies submitted to public databases far
      exceeds the rate of new RNA-seq studies. There is clearly a need for methods that
      make it easier to combine data from different technologies. In this paper, we
      propose a new method for processing RNA-seq data that yields gene expression
      estimates that are much more similar to corresponding estimates from microarray
      data, hence greatly improving cross-platform comparability. The method we call
      PREBS is based on estimating the expression from RNA-seq reads overlapping the
      microarray probe regions, and processing these estimates with standard microarray
      summarisation algorithms. Using paired microarray and RNA-seq samples from TCGA
      LAML data set we show that PREBS expression estimates derived from RNA-seq are
      more similar to microarray-based expression estimates than those from other RNA
      seq processing methods. In an experiment to retrieve paired microarray samples
      from a database using an RNA-seq query sample, gene signatures defined based on
      PREBS expression estimates were found to be much more accurate than those from
      other methods. PREBS also allows new ways of using RNA-seq data, such as
      expression estimation for microarray probe sets. An implementation of the
      proposed method is available in the Bioconductor package "prebs." 

PMID- 25966036
TI  - Hydrophilic Conjugated Polymers with Large Bandgaps and Deep-Lying HOMO Levels as
      an Efficient Cathode Interlayer in Inverted Polymer Solar Cells.
AB  - Two hydrophilic conjugated polymers, PmP-NOH and PmP36F-NOH, with polar diethanol
      amine on the side chains and main chain structures of poly(meta-phenylene) and
      poly(meta-phenylene-alt-3,6-fluorene), respectively, are successfully
      synthesized. The films of PmP-NOH and PmP36F-NOH show absorption edges at 340 and
      343 nm, respectively. The calculated optical bandgaps of the two polymers are
      3.65 and 3.62 eV, respectively, the largest ones so far reported for hydrophilic
      conjugated polymers. PmP-NOH and PmP36F-NOH also possess deep-lying highest
      occupied molecular orbital levels of -6.19 and -6.15 eV, respectively. Inserting
      PmP-NOH and PmP36F-NOH as a cathode interlayer in inverted polymer solar cells
      with a PTB7/PC71 BM blend as the active layer, high power conversion efficiencies
      of 8.58% and 8.33%, respectively, are achieved, demonstrating that the two
      hydrophilic polymers are excellent interlayers for efficient inverted polymer
      solar cells. 

PMID- 25966037
TI  - Deterministic Assembly of Flexible Si/Ge Nanoribbons via Edge-Cutting Transfer
      and Printing for van der Waals Heterojunctions.
AB  - As the promising building blocks for flexible electronics and photonics,
      inorganic semiconductor nanomembranes have attracted considerable attention owing
      to their excellent mechanical flexibility and electrical/optical properties. To
      functionalize these building blocks with complex components, transfer and
      printing methods in a convenient and precise way are urgently demanded. A
      combined and controllable approach called edge-cutting transfer method to
      assemble semiconductor nanoribbons with defined width (down to submicrometer) and
      length (up to millimeter) is proposed. The transfer efficiency can be
      comprehended by a classical cantilever model, in which the difference of stress
      distributions between forth and back edges is investigated using finite element
      method. In addition, the vertical van der Waals PN (p-Si/n-Ge) junction
      constructed by a two-round process presents a typical rectifying behavior. The
      proposed technology may provide a practical, reliable, and cost-efficient
      strategy for transfer and printing routines, and thus expediting its potential
      applications for roll-to-roll productions for flexible devices. 

PMID- 25966039
TI  - Line contribution to the critical Casimir force between a homogeneous and a
      chemically stepped surface.
AB  - Recent experimental realizations of the critical Casimir effect have been
      implemented by monitoring colloidal particles immersed in a binary liquid mixture
      near demixing and exposed to a chemically structured substrate. In particular,
      critical Casimir forces have been measured for surfaces consisting of stripes
      with periodically alternating adsorption preferences, forming chemical steps
      between them. Motivated by these experiments, we analyze the contribution of such
      chemical steps to the critical Casimir force for the film geometry and within the
      Ising universality class. By means of Monte Carlo simulations, mean-field theory
      and finite-size scaling analysis we determine the universal scaling function
      associated with the contribution to the critical Casimir force due to individual,
      isolated chemical steps facing a surface with homogeneous adsorption preference
      or with Dirichlet boundary condition. In line with previous findings, these
      results allow one to compute the critical Casimir force for the film geometry and
      in the presence of arbitrarily shaped, but wide stripes. In this latter limit the
      force decomposes into a sum of the contributions due to the two homogeneous parts
      of the surface and due to the chemical steps between the stripes. We assess this
      decomposition by comparing the resulting sum with actual simulation data for the
      critical Casimir force in the presence of a chemically striped substrate. 

PMID- 25966040
TI  - An anion sensor based on an organic field effect transistor.
AB  - We propose an organic field effect transistor (OFET)-based sensor design as a new
      and innovative platform for anion detection. OFETs could be fabricated on low
      cost plastic film substrates using printing technologies, suggesting that OFETs
      can potentially be applied to practical supramolecular anion sensor devices in
      the near future. 

PMID- 25966041
TI  - Aldehyde capture ligation for synthesis of native peptide bonds.
AB  - Chemoselective reactions for amide bond formation have transformed the ability to
      access synthetic proteins and other bioconjugates through ligation of fragments.
      In these ligations, amide bond formation is accelerated by transient enforcement
      of an intramolecular reaction between the carboxyl and the amine termini of two
      fragments. Building on this principle, we introduce an aldehyde capture ligation
      that parlays the high chemoselective reactivity of aldehydes and amines to
      enforce amide bond formation between amino acid residues and peptides that are
      difficult to ligate by existing technologies. 

PMID- 25966042
TI  - Response to Serum cytokeratin-18 fragment levels predict development of type 2
      diabetes mellitus in adult patients with NAFLD.

PMID- 25966043
TI  - Copper Sediment Toxicity and Partitioning during Oxidation in a Flow-Through
      Flume.
AB  - The bioavailability of transition metals in sediments often depends on redox
      conditions in the sediment. We explored how the physicochemistry and toxicity of
      anoxic Cu-amended sediments changed as they aged (i.e., naturally oxidized) in a
      flow-through flume. We amended two sediments (Dow and Ocoee) with Cu, incubated
      the sediments in a flow-through flume, and measured sediment physicochemistry and
      toxicity over 213 days. As sediments aged, oxygen penetrated sediment to a
      greater depth, the relative abundance of Fe oxides increased in surface and deep
      sediments, and the concentration of acid volatile sulfide declined in Ocoee
      surface sediments. The total pool of Cu in sediments did not change during aging,
      but porewater Cu, and Cu bound to amorphous Fe oxides decreased while Cu
      associated with crystalline Fe oxides increased. The dose-response of the
      epibenthic amphipod Hyalella azteca to sediment total Cu changed over time, with
      older sediments being less toxic than freshly spiked sediments. We observed a
      strong dose-response relationship between porewater Cu and H. azteca growth
      across all sampling periods, and measurable declines in relative growth rates
      were observed at concentrations below interstitial water criteria established by
      the U.S. EPA. Further, solid-phase bioavailability models based on AVS and
      organic carbon were overprotective and poorly predicted toxicity in aged
      sediments. We suggest that sediment quality criteria for Cu is best established
      from measurement of Cu in pore water rather than estimating bioavailable Cu from
      the various solid-phase ligands, which vary temporally and spatially. 

PMID- 25966044
TI  - Comparative toxicities of organophosphate and pyrethroid insecticides to aquatic
      macroarthropods.
AB  - As agricultural expansion and intensification increase to meet the growing global
      food demand, so too will insecticide use and thus the risk of non-target effects.
      Insecticide pollution poses a particular threat to aquatic macroarthropods, which
      play important functional roles in freshwater ecosystems. Thus, understanding the
      relative toxicities of insecticides to non-target functional groups is critical
      for predicting effects on ecosystem functions. We exposed two common
      macroarthropod predators, the crayfish Procambarus alleni and the water bug
      Belostoma flumineum, to three insecticides in each of two insecticide classes
      (three organophosphates: chlorpyrifos, malathion, and terbufos; and three
      pyrethroids: esfenvalerate, lambda-cyhalothrin, and permethrin) to assess their
      toxicities. We generated 150 simulated environmental exposures using the US EPA
      Surface Water Contamination Calculator to determine the proportion of estimated
      peak environmental concentrations (EECs) that exceeded the US EPA level of
      concern (0.5*LC50) for non-endangered aquatic invertebrates. Organophosphate
      insecticides generated consistently low-risk exposure scenarios (EECs<0.5*LC50)
      for both P. alleni and B. flumineum. Pyrethroid exposure scenarios presented
      consistently high risk (EECs>0.5*LC50) to P. alleni, but not to B. flumineum,
      where only lambda-cyhalothrin produced consistently high-risk exposures. Survival
      analyses demonstrated that insecticide class accounted for 55.7% and 91.1% of
      explained variance in P. alleni and B. flumineum survival, respectively. Thus,
      risk to non-target organisms is well predicted by pesticide class. Identifying
      insecticides that pose low risk to aquatic macroarthropods might help meet
      increased demands for food while mitigating against potential negative effects on
      ecosystem functions. 

PMID- 25966045
TI  - Evaluating sub-lethal effects of orchard-applied pyrethroids using video-tracking
      software to quantify honey bee behaviors.
AB  - Managed honey bee, Apis mellifera L., colonies are contracted to pollinate fruit
      and nut orchards improving crop quality and yield. Colonies placed in orchards
      are potentially exposed to pyrethroid insecticides used for broad-spectrum pest
      control. Pyrethroids have been reported to pose minimal risk to bees due to their
      low application rates in the field and putative repellent properties. This
      repellency is believed to alter foraging behavior with the benefit of preventing
      bees from encountering a lethal dose in the field. However, sub-lethal exposure
      to pyrethroids may adversely impact bee behavior potentially resulting in social
      dysfunction or disruption of foraging. This study quantified behaviors associated
      with sub-lethal exposure to orchard-applied pyrethroids including, lambda
      cyhalothrin, esfenvalerate, and permethrin, using video tracking software,
      Ethovision XT (Noldus Information Technologies). Bee locomotion, social
      interaction, and time spent near a food source were measured over a 24-h period.
      Bees treated with a pyrethroid traveled 30-71% less than control bees. Social
      interaction time decreased by 43% for bees treated with a high sub-lethal dose of
      esfenvalerate. Bees exposed to a high sub-lethal dose of permethrin spent 67%
      less time in social interaction and spent more than 5 times as long in the food
      zone compared to control bees. 

PMID- 25966046
TI  - Comparative cytotoxic response of nickel ferrite nanoparticles in human liver
      HepG2 and breast MFC-7 cancer cells.
AB  - Nickel ferrite nanoparticles (NPs) have received much attention for their
      potential applications in biomedical fields such as magnetic resonance imaging,
      drug delivery and cancer hyperthermia. However, little is known about the
      toxicity of nickel ferrite NPs at the cellular and molecular levels. In this
      study, we investigated the cytotoxic responses of nickel ferrite NPs in two
      different types of human cells (i.e., liver HepG2 and breast MCF-7). Nickel
      ferrite NPs induced dose-dependent cytotoxicity in both types of cells, which was
      demonstrated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide
      (MTT), neutral red uptake (NRU) and lactate dehydrogenase (LDH) assays. Nickel
      ferrite NPs were also found to induce oxidative stress, which was evident by the
      depletion of glutathione and the induction of reactive oxygen species (ROS) and
      lipid peroxidation. The mitochondrial membrane potential due to nickel ferrite NP
      exposure was also observed. The mRNA levels for the tumor suppressor gene p53 and
      the apoptotic genes bax, CASP3 and CASP9 were up-regulated, while the anti
      apoptotic gene bcl-2 was down-regulated following nickel ferrite NP exposure.
      Furthermore, the activities of apoptotic enzymes (caspase-3 and caspase-9) were
      also higher in both types of cells treated with nickel ferrite NPs. Cytotoxicity
      induced by nickel ferrite was efficiently prevented by N-acetyl cysteine (ROS
      scavenger) treatment, which suggested that oxidative stress might be one of the
      possible mechanisms of nickel ferrite NP toxicity. We also observed that MCF-7
      cells were slightly more susceptible to nickel ferrite NP exposure than HepG2
      cells. This study warrants further investigation to explore the potential
      mechanisms of different cytotoxic responses of nickel ferrite NPs in different
      cell lines. 

PMID- 25966047
TI  - Distribution and age-related bioaccumulation of lead (Pb), mercury (Hg), cadmium
      (Cd), and arsenic (As) in tissues of common carp (Cyprinus carpio) and European
      catfish (Sylurus glanis) from the Busko Blato reservoir (Bosnia and Herzegovina).
AB  - The purpose of this study was to quantify the bioaccumulation of Pb, Hg, Cd, and
      As in tissues of carp (Cyprinus carpio) and catfish (Silurus glanis) from Busko
      Blato in Bosnia and Herzegovina. Arsenic concentrations were below the Maximal
      Admissible Concentration (MAC) for Croatia and other countries. Mercury
      concentrations were below 1 mg kg(-1), but in most muscle samples of both species
      and all catfish liver samples, the values were higher than 0.5 mg kg(-1) (higher
      than the MAC for many countries including Croatia). Lead concentrations were
      higher than 1 mg kg(-1) (the MAC for Croatia) in most muscle samples; all kidney
      and most catfish liver samples also exceeded 1 mg kg(-1). Cadmium concentrations
      in all tissues, other than the gonads, were higher than 0.1 mg kg(-1) (MAC for
      Croatia), with the highest concentrations found in the kidneys. The only gender
      difference was found in carp, where a 68.4% higher concentration of As was found
      in the fry compared to the milt (P<0.05). Concentrations of all of the elements
      were higher in catfish compared to carp for most tissues. Significant
      correlations were found between all of the elements in the muscles and the liver
      of carp. In catfish, the muscles were the only tissue in which multiple
      correlations were found. Linear positive correlations with age and body mass were
      demonstrated for the concentrations of all heavy metals for all tissues except
      the gonads in both fish species. We concluded that significant heavy metal
      accumulation in carp and a catfish tissues correlates with age and body mass;
      bioaccumulation is species- and tissue-specific and is different for each
      element.

PMID- 25966048
TI  - Fluoride exposure changed the structure and the expressions of reproductive
      related genes in the hypothalamus-pituitary-testicular axis of male mice.
AB  - Numerous studies have shown that fluoride exposure adversely affected the male
      reproductive function, while the molecular mechanism is not clear. The present
      study was to investigate the effects of fluoride exposure (60 days) on the
      expressions of reproductive related genes, serum sex hormone levels and
      structures of the hypothalamus-pituitary-testicular axis (HPTA), which plays a
      vital role in regulating the spermatogenesis in male mice. In this study, 48 male
      mice were administrated with 0, 25, 50, and 100 mg/L NaF through drinking water.
      Results showed that the malformation ratio of sperm was significantly increased
      (P<0.05). At transcriptional level, the expression levels of follicle-stimulating
      hormone receptor (FSHR), luteinizing hormone receptor (LHR), inhibin alpha
      (INHalpha), inhibin beta-B (INHbetaB), and sex hormone binding globulin (SHBG)
      mRNA in testis were significantly decreased (P<0.05). Moreover, histological
      lesions in testis and ultrastructural alterations in hypothalamus, pituitary and
      testis were obvious. However, the same fluoride exposure did not lead to
      significant changes of related mRNA expressions in hypothalamus and pituitary
      (P>0.05). Also, there were no marked changes in serum hormones. Taken together,
      we conclude that the mechanism of HPTA dysfunction is mainly elucidated through
      affecting testes, and its effect on hypothalamus and pituitary was secondary at
      exposure for 60 days.

PMID- 25966049
TI  - Testing single extraction methods and in vitro tests to assess the geochemical
      reactivity and human bioaccessibility of silver in urban soils amended with
      silver nanoparticles.
AB  - To assess if the geochemical reactivity and human bioaccessibility of silver
      nanoparticles (AgNPs) in soils can be determined by routine soil tests commonly
      applied to other metals in soil, colloidal Ag was introduced to five pots
      containing urban soils (equivalent to 6.8 mg Ag kg(-1) soil). Following a 45 days
      stabilization period, the geochemical reactivity was determined by extraction
      using 0.43 M and 2 M HNO3. The bioaccessibility of AgNPs was evaluated using the
      Simplified Bioaccessibility Extraction Test (SBET) the "Unified BARGE Method"
      (UBM), and two simulated lung fluids (modified Gamble's solution (MGS) and
      artificial lysosomal fluid (ALF)). The amount of Ag extracted by 0.43 M and 2 M
      HNO3 soil tests was <8% and <50%, respectively of the total amount of Ag added to
      soils suggesting that the reactivity of Ag present in the soil can be relatively
      low. The bioaccessibility of Ag as determined by the four in vitro tests ranged
      from 17% (ALF extraction) to 99% (SBET) indicating that almost all Ag can be
      released from soil due to specific interactions with the organic ligands present
      in the simulated body fluids. This study shows that to develop sound soil risk
      evaluations regarding soil contamination with AgNPs, aspects of Ag biochemistry
      need to be considered, particularly when linking commonly applied soil tests to
      human risk assessment.

PMID- 25966050
TI  - Bioaccessibility of metals and human health risk assessment in community urban
      gardens.
AB  - Pseudo-total (i.e. aqua regia extractable) and gastric-bioaccessible (i.e.
      glycine+HCl extractable) concentrations of Ca, Co, Cr, Cu, Fe, Mn, Ni, Pb and Zn
      were determined in a total of 48 samples collected from six community urban
      gardens of different characteristics in the city of Madrid (Spain). Calcium
      carbonate appears to be the soil property that determines the bioaccessibility of
      a majority of those elements, and the lack of influence of organic matter, pH and
      texture can be explained by their low levels in the samples (organic matter) or
      their narrow range of variation (pH and texture). A conservative risk assessment
      with bioaccessible concentrations in two scenarios, i.e. adult urban farmers and
      children playing in urban gardens, revealed acceptable levels of risk, but with
      large differences between urban gardens depending on their history of land use
      and their proximity to busy areas in the city center. Only in a worst-case
      scenario in which children who use urban gardens as recreational areas also eat
      the produce grown in them would the risk exceed the limits of acceptability. 

PMID- 25966052
TI  - Diterpenoids and Triterpenoids from the Resin of Bursera microphylla and Their
      Cytotoxic Activity.
AB  - A chemical study of the nonpolar fraction of a methanol-soluble extract of
      Bursera microphylla resin yielded a variety of di- and triterpenoids. In total,
      15 compounds were isolated, of which three are new, namely, malabaricatrienone
      (1), malabaricatrienol (2), and microphyllanin (3). The antiproliferative
      activity of the major compounds was evaluated in different murine cancer cell
      lines (M12.C3.F6 and RAW264.7) and human cancer cells (A549, HeLa, and PC-3). The
      new compounds (1-3) did not show significant antiproliferative activity. The
      known compounds ariensin (4), burseran (5), and dihydroclusin diacetate (6) were
      effective against the RAW264.7 cell line, with IC50 values in the micromolar
      range. 

PMID- 25966053
TI  - Retired or not, the theory of planned behaviour will always be with us.

PMID- 25966055
TI  - Role of APN and TNF-alpha in type 2 diabetes mellitus complicated by nonalcoholic
      fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease caused by
      non-excessive alcohol consumption and is the most common cause of elevated levels
      of serum liver enzymes. We examined changes in adiponectin (APN) and tumor
      necrosis factor-alpha (TNF-alpha) in type 2 diabetes mellitus (T2DM) complicated
      by NAFLD and their relationships with insulin resistance (IR). Forty-two T2DM, 39
      NAFLD, and 45 T2DM complicated with NAFLD (complicated group) patients were
      enrolled in this study. Body mass index, fasting blood plasma glucose (FPG),
      fasting insulin, triglyceride (TG), alanine aminotransferase, gamma-glutamyl
      transpeptidase, APN, TNF-alpha, and homeostasis model of assessment (HOMA)-IR
      were determined. The degree of fatty liver was graded according to liver/spleen
      computed tomography ratio and intrahepatic vessel manifestations. Compared with
      the T2DM and NAFLD groups, fasting blood plasma glucose, alanine
      aminotransferase, gamma-glutamyl transpeptidase, TG, TNF-alpha, and HOMA-IR in
      the complicated group were significantly increased, while APN was significantly
      reduced. Body mass index in the complicated group was significantly higher than
      in the T2DM group. The complicated group was prone to severe fatty liver compared
      with the NAFLD group. APN was negatively correlated with body mass index, fasting
      blood plasma glucose, TG, TNF-alpha, and HOMA-IR. TNF-alpha was negatively
      correlated with APN, but positively correlated with FPG, fasting insulin, TG, and
      HOMA-IR. The complicated group had clear IR. A more severe degree of fatty liver
      was associated with higher HOMA-IR and TNF-alpha and lower APN. APN was an
      important factor for antagonizing inflammation and mitigating IR. 

PMID- 25966056
TI  - A multiplex panel of short-amplicon insertion-deletion DNA polymorphisms for
      forensic analysis.
AB  - We have previously developed a panel of 40 insertion-deletion (INDEL) human DNA
      polymorphisms that was proven to ad-equately cover the span of global human
      genetic diversity. The panel was found to have very low matching probabilities
      with respect to both the global and Brazilian populations. To optimize the panel
      for application with degraded DNA samples, which are commonly encountered in fo
      rensic analysis, we have significantly reduced the amplicon size of the INDELs
      and developed a new multiplex panel. The panel has an ampli-con size ranging from
      50 to 153 base pairs, with a mean of 93 base pairs. It could be amplified by
      polymerase chain reaction in two multiplex re-actions, which were then combined
      for electrophoretic separation and identification of the individual products in
      the ABI3130 four-color DNA analyzer. The results of the new panel were fully
      validated. 

PMID- 25966057
TI  - Case Report: Local skin flap with vacuum-seal drainage to facilitate healing of
      ACS.
AB  - The purpose of this study was to analyze the therapy of a severe abdominal
      compartment syndrome (ACS) to elucidate the use of an abdominal advanced flap
      with other supportive measures for restoration of large defects of the abdominal
      wall. A patient presented with a large defect of the abdominal wall caused by
      ACS, which had resulted from multiple injuries after a fall from height. Healing
      of the defect was achieved by transplantation of an abdominal advanced flap and
      other supportive strategies. All of the treatment measures are presented to
      demonstrate complicated treatment procedures for closure of large defects of the
      abdominal wall. An abdominal advanced flap combined with other supportive
      measures was successfully applied in the healing process of ACS. This study
      examined the treatment of a case of ACS caused by severe abdominal trauma. The
      results demonstrated that a large defect of the abdominal wall caused by ACS
      should be closed as early as possible, and an abdominal advanced flap combined
      with complex supportive measures can be a recommended strategy for closing large
      defects of the abdominal wall. 

PMID- 25966058
TI  - Effects of musk ketone on nerve recovery after spinal cord injury.
AB  - The present study aimed to determine the effects of musk ketone on nerve recovery
      in rats after spinal cord injury. A total of 105 SD female rats were used to
      establish the rat with dorsal spinal cord injury model (modified Allen's method).
      The rats weighed from 200 to 250 g and were provided by the Experimental Animal
      Center of Chongqing Medical University. They were randomly divided into five
      treatment groups: saline (NS group), methylprednisolone (MP group), and musk
      ketone groups (MO1, MO2, and MO3 groups). The Swash plate test and BBB behavioral
      score were used to determine neurological function recovery after spinal cord
      injury. Hematoxylin-eosin (HE) staining was used to detect general structural
      changes in spinal cord tissue. The enzyme-linked immunosorbent assay was used for
      the determination of interleukin 10 (IL-10) in spinal cord tissue. We found that
      compared with the NS control group, critical angle, BBB score and IL-10 levels in
      rat spinal cord tissue significantly increased in the MP group and MO groups 7
      and 14 days after the operation. HE staining showed that in the NS group, there
      was hemorrhage, edema, necrosis, axonal demyelination, inflammatory cell
      infiltration and glial cell response in spinal cord tissue. After 7 days, spinal
      cord edema and inflammation were reduced and neuronal degeneration and necrosis
      were not evident in the MP and MO groups. We conclude that musk ketone can reduce
      secondary damage after spinal cord injury and promote nerve recovery in rats. 

PMID- 25966054
TI  - Genetic profiles of Propionibacterium acnes and identification of a unique
      transposon with novel insertion sequences in sarcoid and non-sarcoid isolates.
AB  - Propionibacterium acnes is one of the most commonly implicated etiologic agents
      of sarcoidosis. We previously reported a complete genome sequence of the C1
      strain of P. acnes as a clinical isolate from subcutaneous granulomatous
      inflammatory lesions in a patient with sarcoidosis. In the present study, we
      initially searched for genetic profiles specific to the C1 strain by core genome
      analysis and multiple genome alignment with database sequences from 76 and 9 P.
      acnes strains, respectively. The analysis revealed that the C1 strain was
      phylogenetically independent and carried an 18.8-kbp transposon sequence unique
      to the sarcoid isolate. The unique composite transposon comprised a novel
      insertion sequence and extrinsic genes from bacteria other than P. acnes.
      Multilocus sequence typing using 24 sarcoid and 36 non-sarcoid isolates revealed
      a total of 28 sequence types (STs), including ST26, which was most frequently
      found without specificity for sarcoid isolates. All 13 ST26 isolates exhibited
      cell-invasiveness and were confirmed to carry the novel insertion sequence and 4
      of the 27 extrinsic CDSs in the transposon, with one exception. ST26 of P. acnes
      with the composite transposon is the most unique strain detected to date and
      should be further examined as a causative strain of sarcoidosis. 

PMID- 25966059
TI  - In vitro differentiation of sperm from male germline stem cell.
AB  - In this study, we developed a model of sperm in vitro differentiation to study
      the mechanism of spermatogenesis. We isolated newborn male germ cells for in
      vitro differentiation. We found that after 4-5 weeks of culture, sperm-like cells
      were occasionally observed in cell co-culture and the feed-layer. After 1-2 weeks
      of culture followed by 4-5 weeks of co-culture, sperm-like cells were observed. 

PMID- 25966060
TI  - Effects of modified Shoutaiwai recipe on integrin beta3 and leukemia-inhibitory
      factor in endometrium of controlled ovarian hyperstimulation mice during the
      implantation window.
AB  - We investigated the effects of a modified Shoutaiwai recipe on integrin beta3 and
      leukemia-inhibitory factor (LIF) in the endometrium of controlled ovarian
      hyperstimulation (COH) mice during the implantation window. Seventy non-pregnant
      mice were randomly divided into 3 groups: a traditional medicine (TCM) treatment
      group (N = 30), an aspirin treatment (N = 30) group, and a control group (N =
      10). After the model was successfully established, mice in the drug treatment
      groups and the control group were respectively treated with the modified
      Shoutaiwai recipe, aspirin, or 0.9% physiological saline. During the implantation
      window of mice, the middle segment of the mouse uterus was recovered, and
      integrin beta3 and LIF expressions in the endometrium were respectively detected
      using an immunohistological two-step method and reverse transcription-PCR.
      Expressions of integrin beta3 and LIF in the endometrium of mice in the TCM
      treatment group were significantly increased compared to aspirin-treated and
      control mice, and those of aspirin-treated mice were increased compared to the
      control group. Our modified Shoutaiwai recipe may improve the endometrial
      receptivity of COH mice by increasing the expression of integrin beta3 and LIF in
      the endometrium during the implantation window. 

PMID- 25966061
TI  - Association between PARK16 gene polymorphisms and susceptibility of Parkinson's
      disease in a Chinese population.
AB  - Recent genome-wide association studies identified 11 risk loci in different
      populations of familial and sporadic Parkinson's disease (PD) patients. Few loci
      have been verified in different European and Asian populations. We also validated
      2 new single-nucleotide polymorphisms, rs947211 and rs823144, in PARK16 to
      explore their association with susceptibility to PD in the Xinjiang Uygur and Han
      populations. This case-control study included 312 PD patients (130 Uygur and 182
      Han) and 359 control subjects (179 Uygur and 180 Han). Polymerase chain reaction
      restriction fragment length polymorphism analysis and DNA sequencing were used to
      detect the rs947211 and rs823144 polymorphism in the PARK16 gene between the
      Xinjiang Uygur and Han populations. Frequencies of the A allele and AA genotype
      (42.1 and 15.7%, respectively) of rs947211 in PD patients were significantly
      lower than those in the control group (54.7 and 28.7%, respectively, P < 0.01). A
      allele and AA genotype frequencies of rs823144 were 56.8 and 31.8% in the PD
      patients group and were 54.1 and 29.3% in the control group; no significant
      difference was found (P > 0.05). In both the Han and Uygur groups, the rs947211
      polymorphism was associated with PD. Haplotype analysis also indicated that the A
      A and G-A haplotypes were associated with PD. We found that the rs947211
      polymorphism may be a susceptibility marker for PD in the Chinese population; the
      A-A and G-A haplotypes may be a protective factor and a risk factor,
      respectively, for PD in the Chinese population. 

PMID- 25966062
TI  - Effects of bisphenol A on decreasing the percentage and promoting the growth of
      stem cell-like cells from SK-N-SH human neuroblastoma cells.
AB  - Bisphenol A (BPA) is an industrial contaminant and is reported to be a risk
      factor associated with the development of tumors. In our previous studies, we
      have shown that BPA promoted the growth of SK-N-SH human neuroblastoma cells and
      increased their invasion and metastasis. In this study, we further investigated
      the effects of BPA and 17beta-estradiol (E2) on the stem cell-like cells from SK
      N-SH cells. Detection of stem cell markers, proliferation assay, and clonogenic
      analysis showed that the side-population (SP) of SK-N-SH cells had properties
      similar to those of stem cells. BPA or E2 exposure decreased the percentage of SP
      cells and the expression of stem cell-marker proteins. BPA and E2 promoted the
      growth of non-SP cells to a greater extent than of SP cells; in addition, they
      significantly increased the growth of SP cells. Thus, BPA has effects on stem
      cell-like cells, which induce tumor formation, and thus, BPA is an environmental
      factor that plays an important role in the development of neuroblastoma. 

PMID- 25966063
TI  - Postpartum pelvic floor function performance after two different modes of
      delivery.
AB  - This study investigated the incidences of urinary incontinence and pelvic organ
      prolapse as well as pelvic floor muscle strength after cesarean section and
      vaginal delivery. From June 2010 to July 2011, 149 puerpera in Shenzhen Hospital,
      Peking University, were divided into the cesarean section group (N = 66) and the
      vaginal delivery group (N = 83). Postpartum urinary incontinence analysis, pelvic
      examination, and pelvic muscle contraction analysis using the PHENIX
      neuromuscular therapy instrument were performed to compare urinary incontinence,
      pelvic organ prolapse, and pelvic floor muscle condition between the 2 groups.
      The incidences of urinary incontinence in the cesarean and vaginal delivery
      groups were 9.09% (6/66) and 16.87% (14/83), respectively (P > 0.05); the
      incidences of pelvic organ prolapse were 53.03% (35/66) and 86.75% (72/83),
      respectively (P < 0.05). There was no significant difference in pelvic muscle
      pressure or electrophysiological examination results between the 2 groups (P >
      0.05). Hence, cesarean section has a protective effect on early postpartum pelvic
      organ prolapse, but the delivery modes do not differ significantly with respect
      to the incidence of postpartum urinary incontinence or pelvic muscle floor muscle
      strength. 

PMID- 25966064
TI  - Relationship between serum GAD-Ab and the genetic polymorphisms of GAD2 and type
      2 diabetes mellitus.
AB  - In this study, we investigated the relationship between serum glutamic acid
      decarboxylase (GAD) autoantibody (Ab) levels and single nucleotide polymorphisms
      (SNPs) of the glutamic acid de-carboxylase 2 (GAD2) 5'-untranslated region and
      the susceptibility to type 2 diabetes in the Han population. The distributions of
      patients with SNPs in the GAD2 5'-untranslated region (rs2236418, rs185649317,
      and rs8190590) and type 2 diabetes and that of the healthy group were genotyped
      and analyzed using Sequenom MassArray SNP genotyp-ing. GAD-Ab levels were also
      detected. The frequency distributions of the AA, AG, and GG genotypes in the
      polymorphic site rs2236418 in the diabetes GAD-Ab-positive group were 45.9, 42.8,
      and 11.4%, respectively, whereas those in the control group were 36.6, 43.7, and
      19.8%, respectively. The difference between the 2 groups was statis-tically
      significant (P < 0.05). Unlike the GG genotype, the AA and AA + AG genotypes
      increased the risk of GAD-Ab (odds ratios (95% confidence intervals) = 2.623
      (1.351-4.937) and 2.152 (1.375-4.202), respectively). The associations of the 3
      SNPs of the GAD2 gene 5'-un-translated region polymorphisms with susceptibility
      to type 2 diabe-tes in the Chongqing Han population were significant. The SNP of
      rs2236418 in the Chongqing Han population of diabetic patients with serum GAD-Ab
      levels was significantly correlated with the SNPs rs185649317 and rs8190590. 

PMID- 25966065
TI  - Clinical observation of umbilical cord mesenchymal stem cell treatment of severe
      systolic heart failure.
AB  - The aim of this study was to evaluate the effectiveness of umbilical cord
      mesenchymal stem cells (MSCs) in the treatment of chronic systolic heart failure.
      Fifty-nine hospitalized patients with heart failure were randomly divided into a
      treatment group (30 patients) and a control group (29 patients). The treatment
      group received treatment with medication as well as intracoronary transplantation
      of umbilical cord MSCs, and the control group, only medication. The cardiac
      structure, function change, and rehospitalization and mortality rates of the 2
      groups were observed before and 1 and 6 months after treatment. One month after
      the transplantation of umbilical cord MSCs, the incidence of fatigue, chest
      tightness, and dyspnea was high in the treatment group. The 6-min walking
      distance of the treatment group was found to be significantly higher than that of
      the control group (P < 0.05); in addition, the NT-proBNP level, left ventricular
      ejection fraction, and mortality rate of the treatment group were statistically
      lower than those of the control group (P < 0.05). Readmission rates showed a
      downward trend, but the difference was not statistically significant (P > 0.05).
      Using umbilical cord MSCs in the treatment of congestive heart failure can help
      improve cardiac remodeling and cardiac function and reduce the mortality rate. 

PMID- 25966066
TI  - Protective effect of ischemia preconditioning on ischemia-reperfusion injury in
      rat liver transplantation.
AB  - We explored the protective effect of ischemia preconditioning (IP) on ischemia
      reperfusion injury in rat liver transplantation. An orthotopic liver
      transplantation model was utilized in the study. A total of 54 Sprague-Dawley
      rats were divided into a control group (group A, no liver transplantation), liver
      transplantation group (group B, heparin Ringer's lactate solution was perfused
      via the portal vein before donor liver collection), and liver transplantation
      with IP group (group C, IP was performed for different time periods before donor
      liver collection). Liver function, B-cell lymphoma 2 expression in hepatic cells,
      cell apoptosis, and cellular ultrastructure changes were detected after surgery.
      After surgery, serum alanine aminotransferase activity was significantly higher
      in group B than in group A, while it was not clearly enhanced in group C and
      decreased progressively with increasing cycles of IP as bile capacity gradually
      increased. Compared with group B, group C showed alleviated injury of hepatic
      cells, increased B-cell lymphoma 2 expression, and a lower apoptosis index. IP
      had a protective effect on ischemia-reperfusion injury in rat liver
      transplantation, and the mechanism correlated with increased B-cell lymphoma 2
      expression in hepatic cells and inhibition of cell apoptosis. 

PMID- 25966067
TI  - Associations between genetic variants in the promoter region of the insulin-like
      growth factor-1 (IGF1) gene and blood serum IGF1 concentration in Hanwoo cattle.
AB  - In this study, we investigated the associations between genetic variants in the
      promoter region of the insulin-like growth factor-1 (IGF1) gene and blood serum
      IGF1 concentration in Hanwoo cattle. Polymerase chain reaction primers were based
      on GenBank accession No. AF404761 and amplified approximately 533-bp segments.
      Newly identified sequences were submitted to GenBank (accession No. DQ267493).
      Sequence analysis revealed that genetic variants were located at a nucleotide
      position 323 for the nucleotide substitution C/A that was first reported in this
      study and positions 326-349 for a repeat motif (CA10-11). The allele frequencies
      of g.323C>A were 0.264 (C) and 0.736 (A) without significant deviation from Hardy
      Weinberg equilibrium. Frequencies of the repeat motif CA(10) and CA(11) were
      0.604 and 0.396, respectively. Statistical analysis revealed that the genetic
      variation g.323C>A was significantly associated with blood serum IGF1
      concentrations with significant additive genetic effects, whereas no associations
      were found for the repeat motif. IGF1 concentrations were positively (r = 0.453)
      and negatively (r = -0.445) correlated with weights in the growing stages (16-21
      months) and late fattening stages (22-30 months), respectively. The results of
      the present study and future genotypic data for Hanwoo beef cattle based on the
      robust genetic variation of IGF1 will provide critical information for genetic
      improvement and will have a large impact on commercial markets. 

PMID- 25966068
TI  - Cloning and expression analysis of a heat shock protein 90 beta isoform gene from
      the gills of Wuchang bream (Megalobrama amblycephala Yih) subjected to nitrite
      stress.
AB  - Heat shock protein 90 (HSP90), a highly conserved and multi-functional molecular
      chaperone, plays an essential role in cellular metabolism and stress response. In
      this study, HSP90 cDNA named MaHSP90 was cloned from Wuchang bream (Megalobrama
      amblycephala) gills by using rapid amplification of cDNA ends. The full-length
      MaHSP90 cDNA is 2674 bp and consists of a 3',5'-untranslated region and a 2250-bp
      open reading frame encoding a 750-amino acid long protein. Identity analysis
      revealed that the amino acid sequence of MaHSP90 is highly conserved. Homology
      analysis and structure comparison further indicated that MaHSP90 should be the
      beta isoform member of the HSP90 family. MaHSP90 mRNA was ubiquitously expressed
      in the liver, heart, muscle, gill, intestine, kidney, and brain. The MaHSP90 mRNA
      levels under nitrite stress were analyzed using real-time quantitative reverse
      transcriptase-polymerase chain reaction (qRT-PCR); the mRNA levels significantly
      increased at 3, 6, and 12 h after nitrite exposure in the gills and then
      stabilized between 24 and 48 h. Furthermore, a similar relationship between mRNA
      expression (qRT-PCR) and HSP90 protein levels (densitometric band analysis) was
      found. Transcriptional analysis of caspase-8 and caspase-9 expression in the
      gills of juvenile M. amblycephala after a 48-h exposure to nitrite suggested that
      MaHSP90 expression is related positively with nitrite-induced apoptosis. Fish
      exposed to nitrite also showed gill damage. Our results suggest that MaHSP90 mRNA
      is constitutively expressed in various tissues and inducible in the gills under
      nitrite stress, suggesting its important role in nitrite stress response. 

PMID- 25966069
TI  - Optimization of SCoT-PCR reaction system in Dactylis glomerata by orthogonal
      design.
AB  - The effects of 5 factors (template DNA, Mg(2+), dNTPs, Taq DNA polymerase, and
      primer) on the polymerase chain reaction (PCR) were investigated to optimize the
      start codon targeted polymor-phism (SCoT)-PCR system of Dactylis glomerata L.,
      using an orthogo-nal design L16 (4(5)). A suitable SCoT-PCR system for D.
      glomerata was established; the 20 MUL reaction volume contained 3.0 mM Mg(2+),
      0.2 mM dNTPs, 1.0 U Taq DNA polymerase, 0.2 MUM primer, 20 ng tem-plate DNA, and
      2 MUL 10X buffer. Each factor had a different effect on the amplification
      reaction, and the concentration of dNTPs had the larg-est effect on the SCoT-PCR
      system. We tested 10 orchardgrass samples to determine and verify the stability
      of the reaction system. The results showed that amplified bands from diverse
      materials were clear, stable, and rich in polymorphisms, indicating that the
      optimized system was very stable. 

PMID- 25966070
TI  - Promotive effect of comprehensive management on achieving blood glucose control
      in senile type 2 diabetics.
AB  - The aim of this study was to evaluate the control of blood glucose and
      glycosylated hemoglobin A1c (HbA1c) and its influencing factors, in elderly type
      2 diabetic mellitus (T2DM) patients undergoing comprehensive management. After
      years of comprehensive prevention of and control measures for diabetes, elderly
      T2DM patients who were receiving long-term health care were comprehensively
      evaluated through an annual physical examination. In addition to routine health
      examination, the patients were required to undergo HbA1c measurement. Among 688
      patients, 652 were men and 36 were women, with a mean age of 78.2 +/- 9.1 years.
      The average HbA1c was 6.6 +/- 0.9%. A total of 50.6% of the patients had HbA1c
      <6.5%, whereas 76.3% had HbA1c <7.0%. Among all patients, 77.1, 46.4, 66.1, 67.8,
      36.3, and 57.4% achieved the target total cholesterol, low-density lipoprotein
      (LDL), high-density lipoprotein (HDL), triglyceride (TG), blood pressure, and
      body mass index (BMI) levels, respectively. The duration of disease and type of
      treatment, as well as the LDL, HDL, TG, BMI, and blood pressure levels, were
      significantly associated with HbA1c control. No patient was admitted because of
      ketoacidosis or hyperosmolar nonketotic diabetic coma in 10 years. Approximately
      half of the T2DM patients achieved the target HbA1c level. The more effective
      blood glucose control observed in our study compared with previous studies can be
      attributed to the effective monitoring of medical conditions and comprehensive
      management of patients. 

PMID- 25966071
TI  - Variation and genetic structure of Tunisian Festuca arundinacea populations based
      on inter-simple sequence repeat pattern.
AB  - Tunisian tall fescue (Festuca arundinacea Schreb.) is an important grass for
      forages or soil conservation, particularly in marginal sites. Inter-simple
      sequence repeats were used to estimate genetic diversity within and among 8
      natural populations and 1 cultivar from Northern Tunisia. A total of 181
      polymorphic inter-simple sequence repeat markers were generated using 7 primers.
      Shannon's index and analysis of molecular variance evidenced a high molecular
      polymorphism at intra-specific levels for wild and cultivated accessions, showing
      that Tunisian tall fescue germplasm constitutes an important pool of diversity.
      Within-population variation accounted for 39.42% of the total variation, but no
      regional differentiation was discernible to designate close relationships between
      regions. Most of the variation (GST = 67%) occurred between populations, rather
      than within populations. The phiST (0.60) revealed high population structuring.
      Additionally, the population structure was independent of the geographic origin
      and was not affected by environmental factors. The unweighted pair group method
      with arithmetic mean tree based on genetic similarity and principal coordinate
      analysis based on coefficient similarity illustrated that continental populations
      from the proximate localities of Beja and Jendouba were genetically closely
      related, while the wild Skalba population from the littoral Tunisian locality was
      the most diverse from the others. Moreover, great molecular similarity of the
      spontaneous population Sedjnane originated from the mountain areas was revealed
      with the local cultivar Mornag. The observed genetic diversity can be used to
      implement conservation strategies and breeding programs for improving forage
      crops in Tunisia. 

PMID- 25966072
TI  - Erlotinib enhances the CIK cell-killing sensitivity of lung adenocarcinoma A549
      cells.
AB  - We examined the effects and molecular mechanism of the epidermal growth factor
      receptor (EGFR) tyrosine kinase inhibitor erlotinib on NKG2D ligand expression in
      human lung adenocarcinoma A549 cells and the cytotoxicity of cytokine-induced
      killer cells. Flow cytometry was used to detect NKG2D ligand expression in A549
      cells under effects of erlotinib and EGFR downstream molecules, including
      LY294002 (phosphoinositide 3-kinase inhibitor), SB203580 (mitogen-activated
      protein kinase inhibitor), and STAT21 (signal transduction and transcription 3
      inhibitor) after 24 h. A lactate dehydrogenase release assay was used to detect,
      at different effector-to-target ratios, the A549 cell killing activity of
      cytokine-induced killer cells before and after treatment with 10 mM erlotinib.
      Erlotinib suppressed MICA expression in A549 cells and upregulated MICB and UL16
      binding protein 1 expression. EGFR downstream molecules mitogen-activated protein
      kinase and signal transduction and transcription 3 inhibitor did not affect the
      expression of NKG2D ligands in A549 cells. The phosphoinositide 3-kinase
      inhibitor reduced MICA expression in A549 cells, while erlotinib enhanced the
      killing sensitivity of cytokine-induced killer cells in A549 cells. The anti-lung
      carcinoma effects of EGFR tyrosine kinase inhibitor were associated with the
      sensitivity of lung cancer cells to enhanced immune cell killing. 

PMID- 25966073
TI  - Molecular cloning and tissue distribution profiles of the chicken R-spondin1
      gene.
AB  - Rspo1 belongs to the Rspo family, which is composed of 4 members (Rspo1-4) that
      share 40 to 60% sequence homology and similar domain organizations, and regulate
      the WNT signaling pathway via a common mechanism. Rspo1 plays a key role in
      vertebrate development and is an effective mitogenic factor of gastrointestinal
      epithelial cells. We report the cloning of chicken Rspo1 and its gene expression
      distribution among tissues. It contained an open reading frame of 783 bp encoding
      a protein of 260 amino acids, and its molecular weight was predicted to be 28.80
      kDa. Reverse transcription-polymerase chain reaction-based gene expression
      analysis indicated that chicken Rspo1 was highly expressed in the stomach muscle
      tissue, but was expressed at low levels in the lung, brain, jejunum, cecum,
      ileum, spleen, pancreas, kidney, and glandular stomach. These results suggest
      that Rspo1 plays a major role in muscular immune protection. 

PMID- 25966074
TI  - Antibody study in canine distemper virus nucleocapsid protein gene-immunized
      mice.
AB  - The gene for the nucleocapsid (N) protein of canine distemper virus was cloned
      into the pMD-18T vector, and positive recombinant plasmids were obtained by
      enzyme digestion and sequencing. After digestion by both EcoRI and KpnI, the
      plasmid was directionally cloned into the eukaryotic expression vector pcDNA; the
      positive clone pcDNA-N was screened by electrophoresis and then transfected into
      COS-7 cells. Immunofluorescence analysis results showed that the canine distemper
      virus N protein was expressed in the cytoplasm of transfected COS-7 cells. After
      emulsification in Freund's adjuvant, the recombinant plasmid pcDNA-N was injected
      into the abdominal cavity of 8-week-old BABL/c mice, with the pcDNA original
      vector used as a negative control. Mice were immunized 3 times every 2 weeks. The
      blood of immunized mice was drawn 2 weeks after completing the immunizations to
      measure titer levels. The antibody titer in the pcDNA-N test was 10(1.62 +/-
      0.164), while in the control group this value was 10(0.52 +/- 0.56), indicating
      that specific humoral immunity was induced in canine distemper virus nucleocapsid
      protein-immunized mice. 

PMID- 25966075
TI  - Characterization of the male-specific lethal 3 gene in the oriental river prawn,
      Macrobrachium nipponense.
AB  - In this study, male-specific lethal 3 homolog (Mnmsl3) was cloned and
      characterized from the freshwater prawn Macrobrachium nipponense (Crustacea:
      Decapoda: Palaemonidae) by rapid amplification of cDNA ends. The deduced amino
      acid sequences of Mnmsl3 showed high-sequence homology to the insect Msl3 and
      contained a conserved chromatin organization modifier domain and an MORF4-related
      gene domain. Real-time quantitative reverse transcription-polymerase chain
      reaction showed that the Mnmsl3 gene was expressed in all the investigated
      tissues, with the highest level of expression in the testis. The expression level
      of Mnmsl3 between males and females was different in the gonad (testis or ovary),
      abdominal ganglion, and heart. The results revealed that the Mnmsl3 gene might
      play roles in regulating chromatin and in dosage compensation of M. nipponense.
      Real-time quantitative reverse transcription-polymerase chain reaction also
      revealed that Mnmsl3 mRNA expression was significantly increased in both 5 and 20
      days post-larvae after metamorphosis, suggesting that Mnmsl3 plays complex and
      important roles in the early embryonic development and sex differentiation of M.
      nipponense. 

PMID- 25966076
TI  - Association between the CYP11B2 gene -344T>C polymorphism and coronary artery
      disease: a meta-analysis.
AB  - Numerous studies have evaluated the association between the CYP11B2 gene -344T>C
      polymorphism and coronary artery disease (CAD) risk. However, the specific
      association is still controversial. To address this issue, PubMed, EMBASE, and
      China National Knowledge Infrastructure databases were searched for eligible
      articles that reported on the relationship between the CYP11B2 gene -344T>C
      polymorphism and CAD, and were published before April 2014. Data from five
      separate studies with 3687 subjects were analyzed by meta-analysis. No
      significant variation in CAD risk was detected by any of the genetic models in
      the overall study population. Taking into account the effect of ethnicity,
      further stratified analyses demonstrated significant association in both
      Caucasian (TT vs TC: OR = 0.80, 95%CI = 0.64-1.00) and Asian populations (TT vs
      TC: OR = 1.25, 95%CI = 1.01-1.54; dominant model: OR = 0.80, 95%CI = 0.66-0.98).
      The pooled ORs were not substantially altered after the exclusion of one study in
      the control group that deviated from Hardy-Weinberg equilibrium, highlighting the
      reliability of our meta-analysis results. In conclusion, this meta-analysis
      suggested that the -344T>C polymorphism in the CYP11B2 gene might be associated
      with susceptibility to CAD in Caucasians and Asians. 

PMID- 25966077
TI  - Brief Note :Variability in the cathelicidin 6 (CATHL-6) gene in Tianzhu white yak
      from Tibetan area in China.
AB  - Cathelicidins are a major family of antimicrobial peptides (AMPs), an important
      component of innate immune system, playing a critical role in host defense and
      disease resistance in virtually all living species. Polymorphism and functional
      studies on cathelicidin of Tianzhu white yak contribute to understanding the
      specific innate immune mechanism in animals living at high altitudes in
      comparison to cattle and domesticated white yak. Thirty-six individuals of
      Tianzhu white yak, originating from the area of three ecotypes (Gansu in China),
      were investigated. The total length of the aligned Yak cathelicidin 6 (CATHL-6)
      sequences was 1923 bp, including six single nucleotide polymorphisms and one
      indel. Ten haplotypes were identified, and phylogenetic analyses resolved those
      10 haplotypes in two clusters. The results indicate that the white yak originated
      from two domestication sites. In addition, lack of significant pairwise
      difference between sequences (Tajima's D = 0.92865, P > 0.10) in the CATHL-6
      region indicates absence of population size expansion in current white yak
      population. 

PMID- 25966078
TI  - Effect of hydroxy safflower yellow A on myocardial apoptosis after acute
      myocardial infarction in rats.
AB  - This study aimed to investigate the effect of hydroxy safflower yellow A (HSYA)
      on myocardial apoptosis after acute myocardial infarction (AMI) in rats. We
      randomly divided 170 male Wistar rats into 6 groups (N = 23): normal control,
      sham, control, SY (90 mg/kg), HSYA high-dose (HSYA-H, 40 mg/kg), and HSYA low
      dose groups (HSYA-L, 20 mg/kg). Myocardial ischemic injury was induced by
      ligating the anterior descending coronary artery, and the degree of myocardial
      ischemia was evaluated using electrocardiography and nitroblue tetrazolium
      staining. Bax and Bcl-2 expressions in the ischemic myocardium were determined
      using immunohistochemical analysis. Peroxisome proliferator-activated receptor
      gamma (PPAR-gamma) expression in the myocardium of rats with AMI was determined
      using reverse transcription-polymerase chain reaction. Compared to rats in the
      control group, those in the HYSA-H, HSYA-L, and SY groups showed a decrease in
      the elevated ST segments and an increase in the infarct size. The rats in the
      drug-treated groups showed a significantly lower percentage of Bax-positive cells
      and a significantly higher percentage of Bcl-2-positive cells than those in the
      control group (P < 0.05). Moreover, mRNA expression of PPAR-gamma in the ischemic
      myocardium of rats in the SY, HSYA-L, and HSYA-H groups was significantly lower
      than that in the control group (P < 0.05). Thus, HSYA and SY can attenuate
      myocardial ischemia in rats, possibly by increasing the level of Bcl-2/Bax, and
      PPAR-gamma may be not a necessary link in this process. 

PMID- 25966079
TI  - Association between genetic polymorphisms of PTGS2 and glioma in a Chinese
      population.
AB  - Several previous studies indicated that genetic polymorphisms in inflammatory
      factor genes were associated with glioma risk. However, the relationship between
      the prostaglandin-endoperoxide synthase 2 (PTGS2) genetic polymorphism and glioma
      remains unclear in the Chinese population. We selected 199 histologically
      confirmed adult glioma patients and 199 cancer-free controls for the present
      study and analyzed the distribution of the PTGS2 genotypes and haplotypes. We
      found that the CC+CT genotype of rs5275 was common in the control group but not
      in the glioma group (P = 0.033). In addition, we found that the frequency of the
      C allele was higher in the control group than in the glioma group (P = 0.014).
      For rs6681231, although we found no significant difference between the 2 groups
      in genotype distribution, we found that the frequency of the C allele was lower
      in glioma patients than in control subjects (P = 0.044). We found no significant
      difference between these 2 groups in the rs689466 genotype and allele
      distributions. Haplotype analysis suggested that the frequency of the C-A-C
      haplotype was significantly lower in glioma patients than in control subjects [P
      = 0.028, odds ratio (OR) = 0.628, 95% confidence interval (CI) = 0.413-0.955].
      However, the frequency of the T-A-G haplotype was higher in glioma patients than
      in control subjects (P = 0.036, OR = 1.418, 95%CI = 1.022-1.967). Therefore,
      polymorphisms in the PTGS2 gene may be associated with glioma susceptibility in
      the Chinese population. 

PMID- 25966080
TI  - Involvement of AP-1 in p38MAPK signaling pathway in osteoblast apoptosis induced
      by high glucose.
AB  - We investigated the effect of p38MAPK/AP-1 (activator protein-1) signaling on the
      apoptosis of osteoblasts induced by high glucose. A lentivirus vector of small
      hairpin RNA (shRNA) targeting p38MAPK was constructed in vitro. Osteoblasts MC3T3
      E1 cultured in vitro were treated with vehicle, high glucose, p38MAPK-shRNA
      transfection, p38MAPK inhibitor, and unrelated shRNA transfection. Apoptosis,
      protein levels of p38MAPK, and activities of AP-1 in MC3T3-E1 osteoblasts were
      measured using TUNEL and flow cytometry, Western blot analysis, and an
      electrophoretic mobility shift assay. Compared with the vehicle group, high
      glucose induced apoptosis of MC3T3-E1 osteoblasts and activated p38MAPK and AP-1.
      p38MAPK-shRNA transfection blocked the effect of high glucose stimulation, and
      the p38MAPK inhibitor showed similar effects as those observed in p38MAPK
      transfection. Unrelated shRNA had no effect on these changes in MC3T3-E1
      osteoblasts induced by high glucose. Therefore, our results suggest that p38MAPK
      shRNA reduce apoptosis of MC3T3-E1 osteoblasts induced by high glucose by
      inhibiting the p38MAPK-AP-1 signaling pathway. 

PMID- 25966081
TI  - Ammonia concentration and relative humidity in poultry houses affect the immune
      response of broilers.
AB  - To investigate the effect of ammonia (NH3) and humidity on the immune response of
      broilers, broilers were exposed to 30 or 70 mg/kg atmospheric NH3 for 21 days.
      Additionally, birds were exposed to 35, 60, and 85% relative humidity (RH). The
      relative weights of lymphoid organs, serum total protein, serum globulin, serum
      albumin, serum lysozyme, proliferation index of peripheral blood lymphocytes, and
      splenic cytokine gene expression were determined. Exposure to 70 mg/kg NH3
      decreased the relative weight of the spleen during the experimental period, serum
      lysozyme concentration in the first and second weeks, and serum globulin
      concentration in the third week. The proliferation of peripheral blood
      lymphocytes was reduced. High levels of NH3 caused increase in IL-1beta gene
      expression in the experimental period and IL-4 gene expression in the first week.
      Birds exposed to 85% RH had lower thymus and bursa of Fabricius weights in the
      third week and serum lysozyme concentration in the first week; IL-1beta and IL-4
      expressions were higher in the second and third weeks and first and second weeks,
      respectively, than in birds exposed to 60% RH. IL-4 expression was lower during
      the first week, and IL-1beta expression was higher during the second week with
      35% RH than with 60% RH. In conclusion, high NH3 level in the poultry house
      suppressed the immune response of broiler chickens. Neither high nor low RH
      benefited the immune response of broilers. Furthermore, there was an interactive
      effect between NH3 and RH on the immune response of broilers. 

PMID- 25966082
TI  - Distinct non-cerebrovascular risk factors for ischemic lacunar stroke and non
      lacunar stroke: preliminary results.
AB  - Stroke is a non-communicable disease of increasing socioeconomic importance in
      aging populations. This study compared the risk factors implicated in two
      subtypes of ischemic stroke: lacunar stroke (LS) and non-lacunar stroke (NLS). A
      retrospective case control study was conducted on a total of 368 patients [220
      cases (59.8%) of NLS and 148 cases (40.2%) of LS] with first-time onset of
      ischemic stroke. Multivariate logistic regression was performed to compare
      multiple non-cerebrovascular risk factors between the two groups. More patients
      with a history of diabetes were found in the NLS than the LS group (40.5 vs
      26.4%), and that both fasting glucose and HbA1C levels before the onset of stroke
      were higher in NLS than LS patients. Multivariate analysis revealed that patients
      with a history of diabetes were 1.57 times more likely to have NLS than LS (OR =
      1.57, 95%CI = 0.95-3.26). Moreover, male patients were more likely to develop NLS
      than females (OR = 1.46, 95%CI = 0.79-2.69), and patients with elevated
      fibrinogen levels were 1.4 times more likely to develop NLS than LS (OR = 1.40,
      95%CI = 1.09-1.80). Additionally, patients who were heavy drinkers (OR = 1.39,
      95%CI = 0.68-2.84) or smokers (OR = 1.62, 95%CI = 0.91-2.89) were more likely to
      develop NLS than LS. Other risk factors, such as hypertension, dyslipidemia, age,
      and average blood pressure, did not differ between the two types of stroke. Thus,
      distinct non-cerebrovascular risk factors (male gender, long history of diabetes,
      elevated fibrinogen, heavy smoking, and heavy drinking) are associated with a
      higher risk of developing non-lacunar stroke than lacunar stroke. 

PMID- 25966083
TI  - Role of interleukin-6 gene polymorphisms in the risk of coronary artery disease.
AB  - We conducted a case-control study to investigate the association between IL-6 
      174 G>C and -572 C>G polymorphisms and the risk of coronary artery disease (CAD).
      We genotyped IL-6 -174 G>C and -572 C>G in 402 patients with CAD and 402 control
      individuals. IL-6 -174 G>C (rs1800795) and -572 C>G (rs1800796) alleles were
      detected by polymerase chain reaction-restriction fragment length polymorphism.
      Patients with CAD were more likely to have a smoking habit, diabetes, and
      hypertension, a high level of triglycerides, and low levels of total cholesterol
      and high- and low-density lipoprotein cholesterol. Multivariate regression
      analyses showed that subjects carrying the IL-6 -174CC genotype had a small but
      significant increased risk of CAD (P = 0.004). Those carrying the IL-6 -174 G>C
      polymorphic variant had a slightly increased risk of CAD in both dominant and
      recessive models. However, we did not find significant association between the IL
      6 -572 C>G polymorphism and risk of CAD. Moreover, a significant interaction was
      found between the IL-6 -174 G>C polymorphism, gender, and smoking habit. Our
      study, therefore, demonstrated that the IL-6 -174 G>C polymorphism is correlated
      with CAD risk, and that this polymorphism shows interactions with both gender and
      smoking. 

PMID- 25966084
TI  - Effects of AFP gene silencing on Survivin mRNA expression inhibition in HepG2
      cells.
AB  - We investigated the effects of alpha-fetoprotein (AFP) gene silencing on Survivin
      expression in HepG2 cells. Small interfering RNA technology was used to
      downregulate AFP expression in HepG2 cells. An enzyme-linked immunosorbent assay
      was used to measure AFP concentration in the supernatant before and after
      transfection. An MTT assay was used to detect cell proliferation activity before
      and after transfection. We performed flow cytometric analysis to detect the cell
      apoptosis rate, and reverse transcription-polymerase chain reaction to detect
      Survivin mRNA levels before and after transfection. Forty-eight hours after
      transfection, AFP concentration in the supernatant of the experimental group
      significantly decreased, hepatocellular carcinoma cell growth was inhibited by
      43.1%, and the apoptosis rate increased by 24.3%. Survivin mRNA expression was
      reduced by 78.0% in HepG2 cells. These indicators in the control group and in the
      blank group did not change significantly. Silencing of AFP expression in HepG2
      cells can effectively inhibit the growth of hepatoma cells and promote apoptosis,
      which may be useful for reducing intracellular Survivin mRNA levels. 

PMID- 25966085
TI  - Benefits of minimizing immunosuppressive dosage according to cytochrome P450 3A5
      genotype in liver transplant patients: findings from a single-center study.
AB  - We evaluated the clinical efficacy of tailoring tacrolimus dosage to cytochrome
      P450 (CYP) 3A5 genotype in liver transplant patients. One hundred patients who
      received tacrolimus-based therapy were included in the retrospective study in
      which the relationship between the tacrolimus blood trough concentration/dosage
      ratio and the CYP3A5 genotype of both donors and recipients was determined.
      Subsequently, 106 patients were continuously enrolled in a prospective study and
      followed-up for 6 months; the relationship between tacrolimus dosage and CYP3A5
      genotype was also determined. Rates of acute rejection, hepatotoxicity, renal
      toxicity, neurotoxicity, hypertension, and hyperglycemia were compared between
      the groups. During the 6 months following liver transplantation, the mean
      tacrolimus concentration/dosage ratio among patients who did not have the
      CYP3A5*1 genotype and who received a transplant from a donor with the same
      genotype (24/100, 24% of patients) was higher than that among patients who did
      have the CYP3A5*1 genotype and/or had a donor with the same genotype (76/100, 76%
      of patients). In the second part of the study, the tacrolimus dosage was tailored
      to CYP3A5 genotype and 24 patients (22.64%) received a lower dose. There was an
      obvious decrease in acute rejection, hepatotoxicity, renal toxicity,
      neurotoxicity, hypertension, hyperglycemia, and Pneumocystis carinii infection
      among the latter group. A lower tacrolimus dose was suitable for about 25% of the
      liver transplant patients, as these patients did not have the CYP3A5*1 genotype
      and received a transplant from a donor with the same genotype. Tailoring the
      tacrolimus dosage according to the CYP3A5 genotype could reduce rejection and
      adverse effects. 

PMID- 25966086
TI  - Evaluation of a modified sampling method for molecular analysis of air
      microflora.
AB  - A serious issue concerning the durability of economically important materials for
      humans related to cultural heritage is the process of biodeterioration. As a
      result of this phenomenon, priceless works of art, documents, and old prints have
      undergone a process of decomposition caused by microorganisms. Therefore, it is
      important to constantly monitor the presence and diversity of microorganisms in
      exposition rooms and storage areas of historical objects. In addition, the use of
      molecular biology tools for conservation studies will enable detailed research as
      well as reduce the time needed to perform the analyses compared with using
      conventional methods related to microbiology and conservation. The aim of this
      study was to adapt the sampling indoor air method for direct DNA extraction from
      microorganisms, including evaluating the extracted DNA quality and concentration.
      The obtained DNA was used to study the diversity of mold fungi in indoor air
      using polymerase chain reaction-denaturing gradient gel electrophoresis in
      specific archives and museum environments. The research was conducted in 2
      storage rooms of the National Archives in Krakow and in 1 exposition room of the
      Archaeological Museum in Krakow (Poland). 

PMID- 25966087
TI  - Genome-wide polymorphisms between the parents of an elite hybrid rice and the
      development of a novel set of PCR-based InDel markers.
AB  - Genome-wide re-sequencing of the Zhenshan 97 (ZS97) and Milyang 46 (MY46) parents
      of an elite three-line hybrid rice developed in China resulted in the generation
      of 9.91 G bases of data with an effective sequencing depth of 11.66x and 11.51x,
      respectively. Detection of genome-wide DNA polymorphisms, single nucleotide
      polymorphisms (SNPs), short insertions/deletions (InDels; 1-5 bp), and structural
      variations (SVs), which is an invaluable variation resource for genetic research
      and molecular marker-assisted breeding, was conducted by comparing whole-genome
      re-sequencing data. A total of 364,488 SNPs, 61,181 InDels and 6298 SVs were
      detected in ZS97 and 364,179 SNPs, 61,984 InDels and 6408 SVs were detected in
      MY46 compared to the 9311 reference sequence. Synteny analysis of the variation
      revealed a total of 77,013 identical and 181,737 different SNPs and 15,021
      identical and 1205 different InDels between ZS97 and MY46, respectively. A total
      of 180 InDels 3-8 bp in length between ZS97 and MY46 were selected for
      experimental validation; 160 polymerase chain reaction products were efficiently
      separated on 6% non-denaturing polyacrylamide gels. Identification of genome-wide
      variation among the parents of the elite hybrid as well as the set of 160
      polymerase chain reaction-based InDel markers will facilitate future genetic
      studies and the molecular breeding of hybrid rice. 

PMID- 25966088
TI  - Study of optimal scheme of spinal image-guided radiotherapy based on expression
      of caspase-3 in spinal cord neurons by orthogonal design.
AB  - The aim of the study was to optimize the biological safety scheme of spinal image
      guided radiotherapy (IGRT) by determining the expression of caspase-3 in spinal
      cord neurons after IGRT. Thirty-six adult male beagles were assigned according to
      a random number table and subjected to IGRT to the 7th-12th canine thoracic
      vertebral bodies under a total dose of 80 Gy over 5 weeks. An immunohistochemical
      method was used to detect the expression of caspase-3 protein in spinal cord
      tissues, and real-time quantitative RT-PCR with SYBR Green I was used to detect
      the expression of caspase-3 mRNA in spinal cord tissues. Analysis of the
      orthogonal experiment results showed that caspase-3 expression in the spinal cord
      neurons was lowest when a single dose of 16 Gy was applied at a dose rate of 4
      Gy/min, and field number of 9, with ray angle being equal. Thus, spinal IGRT
      showed high biological safety, and the best radiotherapy scheme for biological
      safety was single dose of 16 Gy at 4 Gy/min, with 9 fields and equal ray angle. 

PMID- 25966089
TI  - Complete mitochondrial genome of the Cyclemys dentata and phylogenetic analysis
      of the major family Geoemydidae.
AB  - In the present study, the complete mitochondrial (mt) genome of Cyclemys dentata
      was determined using PCR reactions. The structural organization and gene order of
      C. dentata were equivalent to those of most other vertebrates. The mt genome was
      16,489 bp in length, has rich A+T content, consisting of 13 protein-coding genes,
      2 ribosomal RNA genes, 22 transfer RNA genes, and a control region (D-loop). All
      protein-coding genes started with ATG, many genes have complete stop codons,
      except ND2, COX3, ND3, and cyt-b genes had incomplete stop codons of T. The light
      strand replication origin (OL) of C. dentata might fold into a stable stem-loop
      secondary structure, and its loop had 2 nt less than that of the Cyclemys
      atripons OL sequence. The D-Loop of C. dentata contained a central domain (CD), 2
      extended termination associated sequences (ETAS1, ETAS2) and 3 conserved sequence
      blocks (CSB1, CSB2, CSB3). The average length of 20 turtles' mt genomes was
      16,692.5 bp, including 34.1% A, 27.0% T, 26.0% C and 12.9% G. The C. dentata
      mitochondrial genome could provide useful data for further studies on
      phylogenetics and conservation genetics of this species. The phylogenetic
      relationships of the family Geoemydidae were analyzed by maximum-likelihood (ML)
      and neighbor-joining (NJ) based on concatenated sequences of 13 protein-coding
      genes from 20 turtle species. The ML and NJ trees had homologous topologies. The
      results support the existing classification of the genera of Geoemydidae, that C.
      dentata was a sister species of C. atripons, Pyxidea nested in Cuora, and
      Chinemys was synonymous with Mauremys. 

PMID- 25966090
TI  - Correlation between sheep YAP1 temporal and spatial expression trends and MSTN
      and MyoG gene expression.
AB  - The aim of the current study was to investigate the effects of Yes-associated
      protein 1 (YAP1) gene expression after birth on the development of muscle and the
      relationship between YAP1 and myostatin (MSTN) and myogenin (MyoG). Reverse
      transcription polymerase chain reaction was used to analyze the trends in YAP1,
      MSTN, and MyoG temporal and spatial expression levels in various skeletal muscles
      (i.e., longissimus dorsi muscle, soleus muscle, gastrocnemius muscle, and
      extensor digitorum longus) and across 3 different growth stages (i.e., 2 days
      old, 2 and 6 months old) of Hu Sheep. The results showed that YAP1 expression was
      significantly different in the skeletal muscles of sheep; the expression level
      gradually increased with age; it was highly expressed in the gastrocnemius muscle
      and minimally expressed in the longissimus dorsi muscle. MSTN, a negative
      regulator of skeletal muscle development, was minimally expressed in the soleus
      muscle and might be related to the enlargement of muscle fiber diameter. MyoG, an
      important factor in regulating skeletal muscle development, was minimally
      expressed in the longissimus dorsi muscle and extensor digitorum longus, and
      highly expressed in the gastrocnemius and soleus muscles; it might inhibit the
      enlargement of muscle fiber diameter after birth. YAP1 expression was
      significantly (P < 0.05) or extremely significantly (P < 0.01) and positively
      correlated with MSTN and MyoG at 2 days old, 2 and 6 months old. YAP1 expression
      was related to muscle fiber development after birth and might be a candidate gene
      for the regulation of muscle growth. 

PMID- 25966091
TI  - IL-10 and IL-12B gene polymorphisms in a multiethnic Malaysian population.
AB  - Inheritance of polymorphisms in the interleukin (IL)-10 promoter and IL-12B
      genes, which influence cytokine production and activities, may define the balance
      in T helper response in infection and autoimmune diseases. In the present study,
      we investigated the distribution of the IL-10 promoter and IL-12B gene
      polymorphisms in a multiethnic Malaysian population. Overall, our findings
      suggest that the IL-12B and IL-10 -592 genotypes were distributed homogenously
      across all major ethnic groups, including Malays, Chinese, and Indians, except
      for polymorphisms at IL-10 -1082. At this gene locus, the ethnic Chinese showed a
      significantly lower allele frequency of -1082G (2.1%) compared to the Malay
      (12.2%) and Indian (15.3%) populations. Results for the IL-12B and IL-10 gene
      polymorphisms were consistent with those reported for the Asian population, but
      markedly different from those of the African and Caucasian populations. Our
      findings suggest that there are specific genetic variations between different
      ethnic groups, which should be examined in all gene population-based association
      studies. 

PMID- 25966092
TI  - Immune protective mechanism of rMOMP protein ophthalmic vaccine regarding
      intraocular hypertension and retinal optic nerve injury in rats.
AB  - The aim of this study was to explore the immune protective mechanism of rMOMP
      protein vaccine in intraocular hypertension and retinal optic nerve injury in
      rats. The rMOMP protein ophthalmic vaccine was prepared and quality-controlled.
      Sixty normal adult SD rats were randomly divided into two groups to establish a
      chronic ocular hypertension model and an optic nerve injury model. The model rats
      were vaccinated with rMOMP-CS ophthalmic vaccine. Fluorogold retrograde tracing
      was used to observe retinal ganglion cells, and an immunofluorescence method to
      determine the expression of retinal GAP43, CD3, BDNF, and GDNF. rMOMP protein
      ophthalmic vaccine met the requirements for medicinal use. The number of retinal
      ganglion cells (RGCs) of the rMOMP-CS group in the chronic ocular hypertension
      model was significantly higher than that of the CS group (P < 0.05). The count of
      RGCs of the rMOMP-CS group in the optic nerve clamping injury model was
      significantly higher than that of the CS group (P < 0.01). Thus, rMOMP protein
      ophthalmic vaccine can induce an increase in the expression of retinal
      neurotrophic factors, thereby exerting a protective effect on damaged retinal
      optic nerve. 

PMID- 25966093
TI  - Differential gene expression of epigenetic modifying enzymes between Tibet pig
      and Yorkshire in high and low altitudes.
AB  - Epigenetic modifying enzymes play important roles in the adaptation to hypoxia,
      although no studies have examined their expression levels in Tibet pigs. The lung
      is an important functional organ in hypoxia adaptation. In this study, we
      examined the mRNA expression level of 5 enzymes in the lung of Tibet pigs using
      real-time polymerase chain reaction to determine the epigenetic performance of
      hypoxia adaptation. We selected four groups of pig as the study object, which
      were Tibet pig in highland (TH), Yorkshire in highland (YH), Tibet pig in lowland
      (TL), Yorkshire in lowland (YL). Expression of Dnmt1 in Tibet pig was higher than
      that in Yorkshire (P < 0.01), although there was no significant difference
      between different altitudes within each breed. Expression of Dnmt3a was higher in
      Tibet pig than that in Yorkshire (P < 0.01), and higher in pigs from highland
      than that in lowland areas (P < 0.05). Expression of Hdac1 was higher in group TH
      than in Yorkshire (P < 0.01). Expression of Kdm3a was higher in group TH than in
      the rest of the groups (P < 0.01). Expression of Uhrf1 was higher in Tibet pig
      than in Yorkshire (P < 0.01). In conclusion, the expression levels of the 5
      epigenetic modifying genes were higher in group TH than in group YH. Under
      conditions of oxygen deficiency, breed was the most important factor affecting
      DNA methylation and gene expression. 

PMID- 25966094
TI  - Hypoxia-inducible factor-2alpha (HIF-2alpha) mediates the effects of hypoxia on
      the promotion of HeLa cell viability, colony formation, and invasion capacity in
      vitro.
AB  - Hypoxia reduces the oxygen supply to tumor cells and may limit tumor cell growth.
      However, hypoxia promotes tumor cell metabolic adaptation, apoptosis resistance,
      angiogenesis, invasion, and metastasis. Hypoxia-inducible factor-2alpha (HIF
      2alpha) may be responsible for these hypoxia-induced changes. In this study, we
      investigated the effects of hypoxia and HIF-2alpha knockdown in HeLa cells. HIF
      2alpha shRNA lentivirus was used to knock down HIF-2alpha expression; cell
      viability, colony formation, invasion capacity, and gene expression were
      assessed. Hypoxia promoted HeLa cell growth, whereas knockdown of HIF-2alpha
      expression reduced HeLa cell viability under both normoxic and hypoxic
      conditions, with a greater effect observed under hypoxic conditions. Knockdown of
      HIF-2alpha expression also reduced HeLa cell colony formation and invasion
      capacity under both normoxic and hypoxic conditions. Expression of cyclooxygenase
      2 and vascular endothelial growth factor was reduced after knockdown of HIF
      2alpha expression, with a greater effect observed under hypoxic conditions. HIF
      2alpha mediated the hypoxia-induced effect on the promotion of HeLa cell
      viability, colony formation, and invasion capacity in vitro. Further studies are
      needed to confirm the in vivo relevance of hypoxia and HIF-2alpha. 

PMID- 25966095
TI  - Compound heterozygosity of a novel exon 3 frameshift (p.R357P fs*24) mutation and
      Y486D mutation in exon 5 of the UGT1A1 gene in a Thai infant with Crigler-Najjar
      syndrome type 2.
AB  - Mutations in the UGT1A1 gene cause Crigler-Najjar syndrome (CN), which causes non
      hemolytic unconjugated hyperbilirubinemia, and is categorized as CN1 and CN2
      according to the severity of bilirubin levels. The UGT1A1 gene is responsible for
      encoding the liver enzyme uridine diphosphate-glucuronosyltransferase, UGT1A1.
      This protein adds glucuronic acid to unconjugated bilirubin in bilirubin
      metabolism to form conjugated bilirubin. CN2 occurs when UGT1A1 activity is low,
      while CN1 is the absence of UGT1A1 activity; therefore, the CN2 phenotype is not
      as severe as that of CN1. Here, we report a novel allele of compound heterozygous
      mutations in UGT1A1 in a Thai male infant with clinical symptoms of CN2. The
      patient's compound heterozygosity was composed of a novel mutation, c.1069
      1070insC, and the c.1456T>G mutation. The novel c.1069-1070insC mutation
      generated a premature stop codon in exon 4 (p.R357Pfs*24). The healthy parents
      were heterozygous for the c.1069-1070insC mutation (father) and c.1456T>G
      missense mutation (mother). Our results suggest that compound heterozygosity of
      the novel c.1069-1070insC and c.1456T>G (c211 G >A) missense mutation in the
      UGT1A1 gene played a primary role in the development of CN2 unconjugated
      hyperbilirubinemia. 

PMID- 25966096
TI  - Cloning and expression analysis of terpenoid metabolism-related gene NsyCMS in
      Nicotiana sylvestris.
AB  - Terpenoids constitute the main class of secondary metabolites produced in plants
      with industrial, pharmacological, and agricultural interests. Nicotiana
      sylvestris has been widely adopted as a diploid model system in plant biology for
      studies of terpenoid biosynthesis. In this paper, we report the isolation and
      analysis of the 2-C-methyl-d-erythritol 2,4-cyclodiphosphate synthase (CMS) gene
      of the MEP (methylerythritol 4-phosphate) pathway from N. sylvestris. We used
      homologous-based cloning with a RACE method to obtain the full-length coding
      sequence of the NsCMS. Then, the physical and chemical properties, function, and
      three-dimensional structure of the NsyCMS protein were predicted. Fluorogenic
      quantitative PCR was used to conduct an expression analysis at different
      developmental stages of various tissues of the NsyCMS. The sequence of the NsyCMS
      consists of a 954-bp open reading frame and encodes a predicted protein of 317
      amino acids, with a molecular weight of approximately 49.6 kDa and pi of 6.92.
      The in vivo localization of the encoded protein was cytoplasmic with no signal
      peptide, whereas 2 transmembrane regions were found in NsyCMS. The conserved
      domains of typical 2-C-methyl-d-erythritol 2,4-cyclodiphosphate synthase,
      aminotransferase, and pyridoxal phosphate-dependent transferase were found in
      NsyCMS. Differential expression patterns of the NsyCMS were observed throughout
      the different developmental stages and tissues. NsyCMS messenger RNA was
      expressed in all tissues, with the highest level of expression in the seedling
      leaves. NsyMK was expressed at a higher level in the resettling roots. The
      results from our study set the foundation for exploring the terpenoid
      biosynthetic pathways in N. sylvestris. 

PMID- 25966097
TI  - Expression and significance of SATB1 in the development of breast cancer.
AB  - Special AT-rich sequence binding protein 1 (SATB1) is a recently discovered gene
      regulator that can promote the growth and metastasis of breast cancer. However,
      its expression in different stages of breast cancer development have not been
      examined. We explored the role of SATB1 in the development of breast cancer by
      detecting SATB1 expression levels in different stages of breast cancer. SATB1
      expression was determined using an immunohistochemical streptavidin peroxidase
      method; the relationship between clinicopathological features of breast cancer
      and SATB1 expression was analyzed using the X(2) test. Positive rates of SATB1
      protein in normal breast tissue, normal breast ductal hyperplasia tissue,
      precancerous lesions of breast cancer, non-invasive cancer, early invasive
      carcinoma, and invasive breast cancer tissue were, respectively, 6.25 (2/32), 6.4
      (3/47), 20.4 (10/49), 45.0 (9/20), 52.9 (9/17), and 76.6% (72/94). SATB1 in the
      latter 3 groups was significantly higher than in the first 3 groups (P < 0.05).
      The positive rate of SATB1 protein in invasive non-special types of breast cancer
      (88.5%, 54/61) was significantly higher than in the special type of invasive
      breast cancer (54.5%, 18/33) and early invasive breast cancer (52.9%, 9/17) (P <
      0.05). SATB1 protein expression in breast cancer with lymph node metastasis was
      generally increased, and the difference was statistically significant (P < 0.05).
      SATB1 protein expression showed an increasing trend in different stages of breast
      cancer development. Overexpression indicated poor prognosis. 

PMID- 25966098
TI  - Novel genetic male sterility developed in (Capsicum annuum x C. chinense) x C.
      pubescens and induced by HNO2 showing Mendelian inheritance and aborted at
      telophase of microspore mother cell stage.
AB  - A novel genetic male sterile germplasm was developed by successively crossing of
      (C. annuum x C. chinense) x C. pubescens and by chemical mutagenesis in pepper.
      The sterile anthers showed morphological abnormalities, but pistils developed
      normally with fine pollination capability. We investigated fertility segregation
      through sib-crossing of the same strains and test crossing by male sterile plants
      with 6 advanced inbred lines. The results showed that male fertility in the
      pepper was dominant in the F1 generation and segregated at a rate of 3:1 in the
      F2 generation, suggesting that monogenic male sterility was recessive and
      conformed to Mendelian inheritance. Cyto-anatomy analysis revealed that
      microspore abortion of sterile anthers occurred during telophase in the
      microspore mother cell stage when tapetal cells showed excessive vacuolation,
      resulting in occupation of the loculi. The microspore mother cells self
      destructed and autolyzed with the tapetum so that meiosis in pollen mother cells
      could not proceed past the tetrad stage. 

PMID- 25966099
TI  - Expression of beta-defensins in intestines of chickens injected with vitamin D3
      and lipopolysaccharide.
AB  - The objective of this study was to evaluate the effect of vitamin D3 (VD3) on the
      regulation of chicken intestinal beta-defensin genes under normal and
      lipopolysaccharides (LPS) conditions. Four treatment groups were used, including
      a negative control group, VD3-injection group, LPS-injection group, and both VD3
      injection and LPS-injection group. At 4, 24, and 48 h post-injection, intestines
      were collected and RNA was isolated to measure the chicken beta-defensin genes
      with putative vitamin D responsive elements using quantitative polymerase chain
      reaction. Expressions of all 7 chicken beta-defensin genes was detectable in the
      intestines. Significant increases in GAL-6, -7 and -9 were found following LPS
      injection treatment at 4, 24, and 48 h post-injection, respectively, whereas VD3
      injection did not affect the expression of any investigated genes under normal
      conditions. However, the expression of GAL-4, -5, -6, and -10 were
      synergistically upregulated by VD3 in combination with LPS. These results suggest
      that VD3 enhances the immune immunity during LPS challenge by inducing the
      expression of chicken beta-defensin genes when birds are exposed to immune
      stressors. 

PMID- 25966100
TI  - Case Report Serious pulmonary infection in a splenectomized patient with adult
      type 1 Gaucher disease.
AB  - A 49-year-old man with a history of Gaucher disease type 1, resulting in serious
      splenomegaly and eating disorder, was referred to our department and underwent a
      splenectomy under general anesthesia. Gaucher disease is very rare, and its first
      signs are unexplained splenomegaly and hypersplenism. On preoperative
      examination, the patient's platelet count was slightly low, and his other test
      results were normal. Surprisingly, on the first postoperative day, the patient
      developed a lung infection. This gradually progressed to acute respiratory
      distress syndrome with respiratory failure, requiring intubation and mechanical
      ventilation. The patient eventually recovered, and he was discharged after
      receiving antibiotics and other treatments to enhance immunity. However, his
      postoperative lung infection led to a significantly prolonged and expensive
      hospital stay. This case suggests that we must pay close attention to the immune
      dysfunction of patients with Gaucher disease type 1. Anesthesia and surgery with
      accompanying post-traumatic stress can weaken patients' immunity and cause
      susceptibility to severe lung infections. Pulmonary signs and functions should be
      monitored closely during the perioperative period, and, if necessary, gamma
      globulin and thymosin should be administered early in the preoperative or
      postoperative period to enhance immunity. 

PMID- 25966101
TI  - Conventional and contrast-enhanced ultrasound assessment of craniocerebral
      gunshot wounds.
AB  - This study aimed to investigate the characteristic features of craniocerebral
      gunshot wounds by conventional ultrasound (CUS) and evaluate the efficacy of
      contrast-enhanced ultrasound (CEUS) in differentiation of tissue condition in
      wounds. Twenty crossbreed dogs (treatment: N = 15; control: N = 5) were used in
      the study. Pipe-shaped hyperechoes of varying size were found by CUS in most of
      the treated animals. The echoic areas were distinct from the neighboring brain
      tissue and did not change with time. CEUS revealed that the pipe-shaped echo was
      unenhanced in majority of the injured brains and the surrounding tissue was
      either heterogeneously enhanced or unenhanced. Pathological analysis confirmed
      that the contrast-filling-defect area indicated necrotic tissue and the
      heterogeneous minimally enhanced areas indicated degenerative tissue. CUS imaging
      enabled detection of hematomas and CEUS indicated that the filling defect was in
      the center of the hematoma, with enhancement gradually increasing towards the
      periphery. CUS could effectively detect a wound tract, hematoma, and the
      craniocerebral area injured by a gunshot, while CEUS could accurately reveal
      necrotic tissue in the injured area and differentiate the degenerative from
      normal tissue. 

PMID- 25966102
TI  - Isolation and characterization of cancer stem cells from medulloblastoma.
AB  - Brain cancer stem cells are a subset of tumor cells present in several types of
      brain tumor that evade treatment regimens and are responsible for tumor
      recurrence. Recent reports on several tumors have suggested that Hoechst 33342
      dye exclusion is a powerful technique for isolating cancer stem cell-like side
      population (SP) cells. In the present study, we attempted to isolate the SP cells
      from medulloblastoma, a malignant brain tumor in children. The tumor samples
      obtained were subjected to fluorescence-activated cell sorting analysis for SP
      cell isolation. Further, the SP cells were characterized by a sphere-formation
      assay and analyzed for expression of stem cell genes by reverse transcription
      polymerase chain reaction (RT-PCR). Using flow cytometry, we isolated 2.9% of
      cancer stem-like SP cells from malignant medulloblastoma, which was reduced to
      0.4% in the presence of verapamil, an inhibitor of ABC transporter. These SP
      cells undergo rapid proliferation and have a high tendency to form tumor spheres
      when compared with non-SP cells. Further, RT-PCR analysis revealed that the
      isolated SP cells have increased expression of neural stem cell markers such as
      nestin, Notch1, and the ABC transporter protein ABCG2. Therefore, our findings
      suggest that SP cells of medulloblastoma share the characteristics of cancer stem
      cells. The increased expression of stem cell markers and ABCG2 protein may
      function collectively and be responsible for drug and apoptosis resistance, as
      well as tumor recurrence and invasion. 

PMID- 25966103
TI  - Changes to the migratory inhibitory factor, IL-17, and IL-10 levels in serum from
      chronic hepatitis B patients and clinical significance following Baraclude((r))
      treatment.
AB  - This study aimed to determine the relationship between changes in the serum
      levels of macrophage migratory inhibitory factor (MIF), interleukin (IL) 17, and
      IL-10 during chronic hepatitis B treatment via Baraclude((r)) (Bristol-Meyers
      Squibb). Thirty-six patients with chronic hepatitis B and 24 healthy individuals
      were selected as the experimental and control groups, respectively, and the serum
      levels of MIF, IL-17, and IL-10 were measured during the period in which the
      experimental group was treated with oral Baraclude((r)); meanwhile, the alanine
      aminotransferase (ALT), hepatitis B virus (HBV) DNA, and HBV marker (M) levels
      were measured in the experimental group. In the experimental group, the ALT and
      HBV-DNA levels began to exhibit obvious decreases in week 4, and the MIF and IL
      17 levels exhibited obvious increases in week 4 followed by gradual decreases;
      however, the IL-10 level exhibited an obvious decrease in week 12 and then
      increased gradually. These changes were significant when compared with the
      control group (P < 0.05). In conclusion, Baraclude((r)) treatment not only
      actively suppressed HBV but also indirectly balanced the MIF, IL-17, and IL-10
      levels and reduced the liver inflammatory response. 

PMID- 25966104
TI  - IGFBP-3 A-202C and C2133G polymorphisms and colorectal cancer risk: a meta
      analysis of case-control studies.
AB  - Recent evidence suggests that genetic variations in the IGFBP-3 gene may impact
      susceptibility to colorectal cancer, but individually published results are
      inconclusive. Our meta-analysis was aimed at providing a more precise estimation
      of these associations. An extensive literature search was conducted for
      appropriate articles published before May 1, 2013. This meta-analysis was
      performed using the STATA 12.0 software. The crude odds ratios (OR) with 95%
      confidence interval (CI) were calculated. Eleven case-control studies were
      included with a total of 11,895 colorectal cancer patients and 17,147 healthy
      controls. Our meta-analysis indicated that the G variant of IGFBP-3 C2133G
      polymorphism may be associated with increased colorectal cancer risk. However, no
      statistically significant association was noted between IGFBP-3 A-202C
      polymorphism and colorectal cancer risk. No publication bias was detected in this
      meta-analysis. The current meta-analysis suggests that the IGFBP-3 C2133G
      polymorphism may confer susceptibility to colorectal cancer. The G variant of the
      IGFBP-3 C2133G polymorphism may serve as a useful biomarker for predicting the
      risk of colorectal cancer. 

PMID- 25966105
TI  - Insights about the genetic diversity and population structure of an offshore
      group of common bottlenose dolphins (Tursiops truncatus) in the Mid-Atlantic.
AB  - Although the genus Tursiops has a worldwide distribution and is globally well
      studied, some dolphin populations continue to face high risks of decline. Hence,
      it is necessary to assess the genetic diversity and structure of this genus to
      properly assess its conservation status and to implement appropriate management
      actions. In Brazil, genetic studies on this group remain rare, particularly for
      populations inhabiting offshore waters. Saint Peter and Saint Paul Archipelago
      (SPSPA) is a small group of islands located in the Mid- Atlantic Ridge, where
      recent studies of the Tursiops truncatus group indicate that individuals are
      resident throughout the year around the archipelago, exhibiting considerable site
      fidelity. A previous study with this group indicated that the individuals form an
      isolated population. To test this hypothesis, and describe the genetic diversity
      of SPSPA individuals, we assessed 12 microsatellite loci and a portion of the
      mitochondrial control region. Bayesian analysis revealed that SPSPA bottlenose
      dolphins form a unique population. In a phylogeographic perspective, we found
      that individuals from SPSPA shared mtDNA haplotypes with inshore and offshore
      individuals from North Atlantic, suggesting that they are not currently isolated
      from their conspecifics. Mirroring mtDNA findings, microsatellite analysis
      revealed that most of the pairs of individuals sampled seem to be unrelated
      (83.8%) and no indication of inbreeding, what would be expected if a small
      population such as SPSPA was reproductively isolated. 

PMID- 25966106
TI  - Mutation analysis of PVRL1 in patients with non-syndromic cleft of the lip and/or
      palate in Guangdong.
AB  - Non-syndromic cleft of the lip and/or palate (NSCLP) is a very common birth
      defect; the poliovirus receptor-like 1 gene (PVRL1) has been identified as a
      genetic risk factor for NSCLP in patients from Norway, the Philippines, and South
      America. Given the considerable variation in allele frequencies across these
      geographical regions, this study explored the relationship between NSCLP and
      mutations of PVRL1 in patients from Guangdong, China. We recruited 171 NSCLP
      patients and 100 volunteers, and divided our samples into 2 groups: a sequencing
      group and a mass spectrometry group. In the sequencing group, we screened for
      mutations in exons 2 and 5 of PVRL1 by polymerase chain reaction and direct
      sequencing in 71 NSCLP patients and 100 volunteers. In the mass spectrometry
      group, we screened for amino acid mutations in alpha-spliced transcript codons
      112, 131, and 395, and in the beta-spliced transcript codon 1082 using matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry analysis in
      100 NSCLP patients and 100 volunteers. No mutations were detected in either PVRL1
      exons 2 or 5 in the 71 NSCLP patients and 100 volunteers, nor did we find
      mutations of alpha-spliced transcript codons 112, 131, 395 and the beta-spliced
      transcript codon 1082 in any of the 100 NSCLP patients and 100 volunteers. Thus,
      mutations in exons 2 and 5 of PVRL1, and T334A, A391T, G1183A in the alpha
      spliced transcript, and G1082T in the beta-spliced transcript do not participate
      in the development of NSCLP in patients from Guangdong. 

PMID- 25966107
TI  - Gene expression profiling analysis of 5-hydroxytryptamine signaling pathway in
      rat regenerating liver and different types of liver cells.
AB  - We examined the gene expression profiles of the 5-hydroxytryptamine signaling
      pathway in the regenerating liver and 8 types of liver cells during rat liver
      regeneration, and explored expression differences in 5-hydroxytryptamine
      signaling pathway genes at the level of tissues and cells, as well as the role of
      the pathway on liver regeneration. Eight types of rat regenerating liver cells
      were isolated using Percoll density-gradient centrifugation and immunomagnetic
      bead methods. Rat Genome 230 2.0 Array was used to detect expression changes in 5
      hydroxytryptamine signaling pathway genes. The results showed that 26, 47, 8, 21,
      16, 19, 22, 27, and 20 genes changed significantly in hepatocytes, biliary
      epithelial cells, hepatic stellate cells, oval cells, sinusoidal endothelial
      cells, Kupffer cells, pit cells, dendritic cells, and the regenerating liver,
      respectively. Synthetic effects of 5-hydroxytryptamine signaling pathway genes in
      8 types of liver cells showed that 26 genes were expressed significantly; the
      expression trends of 10 genes were the same in the regenerating liver, while
      others were different. Based on the gene expression profiles of the 8 types of
      liver cells, 5-hydroxytryptamine promoted hepatocyte proliferation through the
      RAS and STAT3 signaling pathways, proliferation and differentiation of sinusoidal
      endothelial cells through the STAT3 signaling pathway, and proliferation and
      apoptosis of pit cells through the AKT3 signaling pathway. There were large
      differences in genes involved in 5-hydroxytryptamine signaling at the tissue and
      cellular levels; thus, liver regeneration should be studied in-depth at the
      cellular level to reveal the molecular mechanism of liver regeneration. 

PMID- 25966108
TI  - Immunomodulatory and clinical effects of the "tiaomian III decoction" in patients
      with blood blocking antibody deficiency and recurrent spontaneous abortion.
AB  - We studied the immunomodulatory and clinical effects of the empirical formula
      "tiaomian III decoction" on maternal blood blocking antibody deficiency and
      recurrent spontaneous abortion. Sixty-one patients with blocking antibody
      deficiency were divided in the experimental group (N = 31), who took tiaomian III
      decoction, and the control group (N = 30), who received active immunotherapy with
      paternal lymphocytes; both treatments lasted 3 months. Blocking antibodies, anti
      idiotypic antibodies, interleukin, T-lymphocyte subsets, and macrophage colony
      stimulating factor (M-CSF) were tested. After treatment, the positive conversion
      rate reached 87.1 and 86.7% in the experimental and control groups, respectively.
      After treatment, CD4 levels decreased while CD8 levels increased in both groups.
      The CD4/CD8 ratio was higher than normal and increased significantly from pre
      treatment (P < 0.05). IL-10 and M-CSF levels increased significantly in both
      groups (P < 0.05). The 1-year conception rates of the experimental and control
      groups were 58.1 and 46.7%, respectively (P < 0.05). The results show the
      tiaomian III decoction can increase the positive conversion rate of maternal
      blocking antibodies and promote the production of IL-10 and M-CSF. Thus, it
      strengthens the maternal body's protection of the fetus and maintenance of
      conception. The higher conception rate of the experimental group demonstrates the
      positive clinic efficacy of the tiaomian III decoction on maternal blood blocking
      antibody deficiency and recurrent spontaneous abortion. 

PMID- 25966109
TI  - Myocardial protective effects of Munziq in myocardial ischemia-reperfusion injury
      rats with abnormal savda syndrome.
AB  - This study evaluated the influence and mechanism of different Munziq doses on
      myocardial ischemia reperfusion injury (MIRI) rats with abnormal savda. Wistar
      rats (N = 96) were divided into the following 8 groups (12 rats each): ischemia
      reperfusion (I/R) model group, high-dose, medium-dose, and low-dose Munziq
      groups, normal I/R group, sham model group, normal sham group, and Atorvastatin
      group. Changes in heart physiology and myocardial morphology after injury with
      MIRI were monitored in each group. Heat shock protein 70 (HSP70) and calcitonin
      gene-related peptide (CGRP) protein expression and serum concentrations of
      superoxide dismutase (SOD), malondialdehyde (MDA), interleukin (IL)-6, and IL-8
      were detected by using western blot and ELISA methods, respectively. The large
      dose Munziq group showed the most significant changes. The VPC incurring time was
      not delayed in the small-dose group, but the accumulative time was significantly
      reduced (P < 0.01). The ventricular tachycardia incurring time did not differ
      significantly between groups. Compared with the normal sham surgical group, the
      I/R groups showed significant increases in HSP70 and CGRP expression (P < 0.01)
      and MDA, IL-6, and IL-8 concentrations (P < 0.05) and a significant decrease in
      the SOD concentration (P < 0.05). Compared with the I/R groups, Munziq
      intervention significantly enhanced HSP70 and CGRP expression (P < 0.01),
      significantly decreased MDA, IL-6, and IL-8 concentrations (P < 0.05), and
      significantly increased the SOD concentration (P < 0.05). In conclusion, Munziq
      intervention improves cardiac physiological function, increases the expression of
      HSP70 and CGRP, and decreases the inflammatory reaction in MIRI model rats. 

PMID- 25966110
TI  - Construction of recombinant human IFNalpha-2b BCG and its antitumor effects on
      bladder cancer cells in vitro.
AB  - We constructed recombinant Bacille Calmette-Guerin (rBCG) that secreted human
      interferon alpha 2b (hIFNalpha-2b), and investigated its antitumor effects on
      bladder cancer cells in vitro. The recombinant plasmid phIFN-alpha-2b was
      constructed using pMAO-4 and transformed into BCG. The supernatant was collected
      at various times and IFN-gamma, interleukin (IL)-12, and tumor necrosis factor
      (TNF)-alpha were detected using an enzyme-linked immunosorbent assay. EJ cells
      were cultivated for 24, 48, and 72 h, together with rBCG, wild-type BCG (wBCG),
      or wBCG+IFN-alpha-2b. rBCG capable of secreting cytokine IFNalpha-2b was
      constructed. On the 4th day of culture, the IFNalpha-2b secreted by rBCG reached
      a maximum. wBCG and rBCG showed no significant difference on cell growth rate
      over 7 days of incubation in 7H9 medium. wBCG and rBCG were both positive for
      acid-fast staining, and showed mycobacterial characteristics of intercellular
      connection in clusters with no clear abnormalities. Higher levels of IFN-gamma,
      TNF-alpha, and IL-12 were induced by rBCG compared with wBCG or MAO4-rBCG (P <
      0.05). rBCG may induce lymphocyte proliferation; the proliferation ratio was
      higher than those induced by wBCG and wBCG+IFN. rBCG had direct anti
      proliferative effects on EJ cells. An MTT assay showed that rBCG inhibited the
      proliferation of bladder cancer cells and had more activity compared with wBCG (P
      < 0.05). The highest anti-tumor activity of lymphocytes was stimulated by rBCG
      (20.31-51.22%). rBCG-IFNalpha-2b induces enhanced cytotoxicity against bladder
      cancer cells in vitro and may be used as an alternative to BCG for bladder cancer
      patients. 

PMID- 25966111
TI  - Effect of curcumin on p38MAPK expression in DSS-induced murine ulcerative
      colitis.
AB  - The aim of this study was to determine the therapeutic effect of curcumin on
      dextran sulfate sodium-induced ulcerative colitis (UC) and to explore the related
      mechanism. Sixty mice were randomly divided into 6 groups. A group was the normal
      control group; B group was the model group; C group was the 1.5 mg/kg
      dexamethasone group based on the B group; and D, E and F groups were 15, 30, and
      60 mg/kg curcumin groups, respectively, based on the B group. The mice were
      killed 7 days after treatment; the expression of TNF-alpha and MPO in colon
      tissue was determined with ELISA, and colon p-p38MAPK and p38MAPK mRNA expression
      was evaluated by immunohistochemistry and RT-PCR, respectively. In the C, D, E,
      and F groups, TNF-alpha and MPO levels significantly decreased (P < 0.05), and
      the expression of p-p38MAPK also significantly decreased (P < 0.01). The
      expression of p38MAPK mRNA in the C, D, E, and F groups decreased (P < 0.01), and
      there was a statistically significant difference between the E and F groups (P <
      0.01). Curcumin had a therapeutic effect, which probably played a role in UC
      treatment by inhibiting the p38MAPK signaling pathway, thereby reducing the
      release of TNF-alpha. 

PMID- 25966112
TI  - Comparative study of clinical efficacy of laparoscopy-assisted radical
      gastrectomy versus open radical gastrectomy for advanced gastric cancer.
AB  - The purpose of this study is to compare the efficacy of laparoscopy-assisted
      radical gastrectomy (LARG) versus that of open radical gastrectomy (ORG).
      Clinical data of 355 patients who underwent radical gastrectomy (160 in the LARG
      group and 195 in the ORG group) were analyzed retrospectively. Efficacy indices
      were compared and analyzed between the two groups. The operating time of LARG was
      longer than that of ORG (228.43 +/- 34.77 versus 207.59 +/- 28.39 min). However,
      patients in the LARG group lost less blood than did those in the ORG group
      (169.46 +/- 82.92 versus 193.86 +/- 82.09 mL), and more lymph nodes were removed
      in the LARG group (19.84 +/- 4.7 versus 18.04 +/- 4.14 per case). The recovery of
      intestinal function was faster (3.72 +/- 1.03 versus 4.41 +/- 1.30 days) in the
      LARG group. Patients in the LARG group were administered a semi-fluid diet
      earlier (5.66 +/- 2.27 versus 7.09 +/- 2.33 days) and had a shorter hospital stay
      (9.44 +/- 3.06 versus 11.07 +/- 7.91 days) than did those in the ORG group, and
      these differences were statistically significant (P < 0.05). No significant
      differences were found in the length of proximal and distal resection margin and
      the incidence of complications (P > 0.05) between the two groups. Thus, LARG is
      safe, feasible, and effective for treating advanced gastric cancer. 

PMID- 25966113
TI  - Highly efficient one-step PCR-based mutagenesis technique for large plasmids
      using high-fidelity DNA polymerase.
AB  - Gene mutation plays an important role in molecular biological studies. A highly
      efficient one-step polymerase chain reaction-based mutagenesis technique for site
      directed mutagenesis was developed in this study. One complementary pair of
      primers was designed that contained the desired mutations in the middle of the
      primers. The amplification products of mutation were amplified using a high
      fidelity DNA polymerase and the original plasmid templates were digested by DpnI.
      This method was successfully used to introduce mutations in two different-sized
      plasmids (12 and 6 kb) with high efficiency. The results indicate that this
      technique can be widely used to introduce any plasmid mutations quickly and
      efficiently. 

PMID- 25966114
TI  - Relationship between EPHX2 gene polymorphisms and essential hypertension in
      Uygur, Kazakh, and Han.
AB  - We investigated the association between rs751141 polymorphisms in the EPHX2 gene
      and essential hypertension in Uygur, Kazakh, and Han subjects in Xinjiang, China.
      A total of 302 essential hypertensive patients in Uygur, 267 in Kazakh, and 368
      in Han, as well as 323 normotensive controls in Uygur, 284 in Kazakh, and 348 in
      Han were enrolled in this study. The TaqMan assay was used to detect the rs751141
      G/A gene polymorphism in EPHX2. The rs751141 G/A genotype frequencies for the
      GA+AA genotypes were 40.2% in essential hypertensive subjects and 52.0% in
      control subjects in the Han population. The frequencies were significantly
      different between the 2 Han groups (P < 0.01). The rs751141G/A gene polymorphism
      showed no significant difference between essential hypertensive patients and
      normotensive controls in Kazakh and Uygur (all P > 0.05). Essential hypertension
      in Xinjiang was associated with the rs751141 G/A allele gene polymorphism in
      EPHX2 in Han subjects but not in Kazakh and Uygur subjects. The rs751141 allele
      gene polymorphism may be an independent protective factor against essential
      hypertension in the Han population. 

PMID- 25966115
TI  - Relative quantification of beta-casein expression in primary goat mammary
      epithelial cell lines.
AB  - Primary mammary epithelial cell cultures were established from mammary tissue of
      lactating and non-lactating goats to assess the expression of beta-casein (CSN2)
      in vitro. Primary cell cultures were established by enzymatic digestion of
      mammary tissue and characterized using antibodies against cytokeratin 14,
      cytokeratin 18, and vimentin. The established primary cell lines in the second
      passage were grown in basal medium on plastic and in hormone-supplemented
      (lactogenic) medium on plastic and on an extracellular matrix-covered surface,
      respectively. CSN2 gene expression was evaluated using quantitative reverse
      transcription PCR. The presence of CSN2 transcripts was detected in all samples,
      including cells originating from non-lactating goat, grown in basal medium. The
      presence of CSN2 protein was confirmed using immunofluorescence. Response to the
      hormonal treatment and cell morphology differed between the cell lines and
      treatments. In 2 cell lines supplemented with lactogenic hormones in the medium,
      CSN2 expression was increased, while CSN2 levels in one of the cell lines
      remained constant, regardless of the treatment. Addition of extracellular matrix
      showed positive effects on CSN2 transcription activity in 1 of the cell lines,
      while in the other 2 showed no statistically significant effects. CSN2 expression
      appeared to depend on subtle differences in physiological state of the starting
      tissue material, growth conditions, cell types present in the culture, and
      methods used for cell culture establishment. Further studies are necessary to
      identify factors that determine hormone-responsiveness and transcriptional
      activity of milk protein genes in goat primary mammary cell cultures. 

PMID- 25966116
TI  - Association between methionine synthase reductase A66G polymorphism and primary
      infertility in Chinese males.
AB  - We examined the association between the methionine synthase reductase (MTRR
      A66G), methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), and
      methionine synthase (MS A2756G) genotypes and non-obstructive male infertility in
      a Chinese population. This case-control study included 162 infertile Chinese
      patients with azoospermia (N = 100) or oligoasthenozoospermia (N = 62) and 120
      fertile men as controls. The polymorphisms MTRR A66G, MTHFR C677T, A1298C, and MS
      A2756G were identified by direct DNA sequencing and the results were
      statistically analyzed. We found no association between the incidence of any of
      these variants in azoospermia patients and control populations. The frequency of
      the MTRR66 polymorphic genotypes (AG, AG+GG) was significantly higher in the
      oligoasthenozoospermia group compared to the controls (P = 0.013, 0.012). Our
      findings revealed an association between the single-nucleotide polymorphism A66G
      in the MTRR gene and male infertility, particularly in oligoasthenozoospermia
      males, suggesting that this polymorphism is a genetic risk factor for male
      infertility in Chinese men. 

PMID- 25966117
TI  - Study of the significance of iron deficiency indexes and erythrocyte parameters
      in anemic pregnant women and their newborns.
AB  - This study aimed to analyze the iron deficiency index and erythrocyte parameters
      in anemic pregnant women and their newborns, and explore their implications for
      anemia during pregnancy. Pregnant women (70) in the third trimester with
      hemoglobin (Hb) <100 g/L who registered and delivered from June 2012-2013 were
      randomly selected as the observation group, 70 pregnant women at similar
      gestational ages with Hb >110 g/L were selected as the control group, and 70
      newborns delivered by women in each group were included in corresponding
      offspring observation and control groups, respectively. Periodic physical
      examinations were conducted on the infants, and blood samples were drawn from the
      women and infants at birth, 42 days, 4 months, and 6 months old for detection of
      Hb and soluble transferrin receptor (sTfR) levels. Pregnant women and their 6
      month-old infants in the observation group had significantly different Hb and
      sTfR levels compared to controls (P < 0.01). There were no significant
      differences in Hb and sTfR levels of infants at birth, 42 days, and 4 months old
      (P > 0.05). The detection rate of iron deficiency anemia (IDA) was significant,
      at 61.43% among 6-month-old infants in the observation group and 22.86% among
      controls (P < 0.01). There were no significant differences in the detection rate
      of IDA among infants at birth, 42 days, and 4 months old between observation and
      control groups (P > 0.05). Therefore, anemia during pregnancy is a major
      contributing factor of IDA and subclinical iron deficiency among 6-month-old
      infants. 

PMID- 25966118
TI  - Fragmentation effects and genetic diversity of the key semidecidual forest
      species Metrodorea nigra in Southwestern Brazil.
AB  - Studies of genetic diversity in plant species present in the remaining fragments
      of the Atlantic Forest are very important for understanding their resilience to
      such a degraded ecosystem. We analyzed the genetic diversity of 3 populations of
      the high-density understory species Metrodorea nigra St. Hill. (Rutaceae) located
      in forest remnants in the region of Ribeirao Preto, SP, Brazil (M13-Rib, BSQ-Rib,
      and FAC-Crav), by using simple sequence repeat (SSR) and inter-simple sequence
      repeat (ISSR) molecular markers for conservation purposes. A total of 133
      polymorphic loci were observed in 136 inter-simple sequence repeat loci (average
      of 17 per primer). The Nei genetic diversity (HE) was relatively high considering
      all populations (0.31). The BSQ-Rib population exhibited the highest value
      (0.27), followed by the M13-Rib (0.26) and FAC-Crav (0.24) populations. The
      simple sequence repeat markers analyzed showed a high number of alleles (K =
      104), with an average of 14.85 alleles per locus. The average observed
      heterozygosity was 0.516 and the average expected heterozygosity was 0.771,
      ranging from 0.688 (FAC-Crav) to 0.765 (BSQ-Rib). The fixation indexes showed
      positive and significant differences from zero for all sample sets, indicating
      inbreeding, which may have resulted from the species' mating patterns and the
      barochoric seed dispersal system of M. nigra. Both markers indicated
      differentiation among populations, with higher values observed for inter-simple
      sequence repeat markers. No significant differences between juvenile and adult
      generations in any of the fragments were observed, indicating the resilience of
      M. nigra to the effects of fragmentation and reduced habitat. 

PMID- 25966119
TI  - Correlation of MSH3 polymorphisms with response and survival in advanced non
      small cell lung cancer patients treated with first-line platinum-based
      chemotherapy.
AB  - Mismatch repair (MMR) genes, as well as the nucleotide excision repair genes,
      play an important role in removing cisplatin-DNA adducts, and the mutation of MMR
      genes in tumors can lead to a decreased response to platinum-based therapies. We
      examined MutS homolog 3 (MSH3), a mismatch repair gene, and whether polymorphisms
      of MSH3 were associated with response and survival in advanced non-small cell
      lung cancer (NCSLC) patients who were treated with platinum-based chemotherapy.
      The peripheral blood of 180 advanced NCSLC patients who were treated with first
      line platinum-based chemotherapy was collected to determine the patients'
      genotypes of MSH3. The three genotypes of the MSH3 polymorphisms rs26279,
      rs1650697 and rs1105524 were investigated. A statistically significant
      association was observed between the polymorphism rs26279 (Ala1054Thr) and
      sensitivity to platinum-based chemotherapy (P = 0.014). A significant correlation
      was found between rs1105524 and progression-free survival (PFS), with the G/A and
      A/A genotypes (median survival time: 14.27 months; 95%CI = 9.80-18.75) suffering
      shorter survival than patients with the G/G genotype (median survival time: 26.37
      months; 95%CI = 15.03-37.71) (P = 0.04). Our results showed that single
      nucleotide polymorphisms in MSH3 had an impact on the chemotherapy response and
      prognosis of advanced NCSLC patients who were treated with platinum-based
      chemotherapy. 

PMID- 25966120
TI  - Dual role of vitamin D-binding protein 1F allele in chronic obstructive pulmonary
      disease susceptibility: a meta-analysis.
AB  - Vitamin D-binding protein (DBP), a highly polymorphic serum protein, encoded by
      GC gene, is important in the development of chronic obstructive pulmonary disease
      (COPD). This meta-analysis was performed to assess the association between GC
      polymorphisms (1F, 1S, and 2 alleles) and COPD susceptibility. Published case
      control studies were retrieved from the Pubmed, Embase, and China National
      Knowledge Infrastructure databases. After data extraction, pooled odds ratios
      (ORs) with 95% confidence intervals (CIs) were calculated. Seven case-control
      studies were included. Pooled effect size showed that GC polymorphisms were not
      significantly associated with COPD susceptibility. According to ethnicity, the 1F
      allele was significantly correlated with COPD susceptibility in Asians (1F vs 1S,
      OR: 1.52, 95%CI: 1.16-2.00 and 1F vs 2, OR: 1.87, 95%CI: 1.42-2.44), indicating
      that individuals with the 1F allele have an increased risk of COPD compared to
      those with the 1S or 2 allele. However, the 1F allele was associated with a
      lower, insignificant risk of COPD than the 1S and 2 alleles in Caucasians (1F vs
      1S, OR: 0.83, 95%CI: 0.64-1.08 and 1F vs 2, OR: 0.73, 95%CI: 0.54-0.98).
      Moreover, no significant association was found for the 1S and 2 alleles in Asians
      (OR: 1.23, 95%CI: 0.90- 1.69) and Caucasians (OR: 0.89, 95%CI: 0.70-1.13). After
      excluding each study, the pooled results were robust and no publication bias was
      observed. We found that the GC 1F allele confers a risk of COPD in Asians,
      whereas the 1F allele may protect against COPD in Caucasians. 

PMID- 25966121
TI  - Isolation and characterization of novel polymorphic microsatellite loci in Atrina
      vexillum Born (Pinnidae).
AB  - The pen shell, Atrina vexillum Born, is an edible shellfish that is widely
      consumed in the Asia-Pacific region. In this study, 11 polymorphic microsatellite
      loci were isolated from A. vexillum, and 30 wild individuals were used to
      evaluate the degree of polymorphism of these markers. The number of alleles per
      locus ranged from 3 to 8. The polymorphism information content varied from 0.199
      to 0.831. The observed and expected heterozygosities were 0.1000-0.8667 and
      0.1244-0.8356, respectively. Two loci deviated significantly from the Hardy
      Weinberg equilibrium (HWE) after a Bonferroni correction, while the other nine
      loci were at HWE. These microsatellite loci will be useful in further studies on
      population genetic analyses, and will provide important genetic data for the
      conservation and recovery of A. vexillum. 

PMID- 25966122
TI  - Role of TGFB1 polymorphism in the development of metastatic brain tumors in non
      small cell lung cancer patients.
AB  - We conducted a case-control study to investigate the role of 3 single-nucleotide
      polymorphisms of the gene encoding transforming growth factor-b1 (TGFB1) in the
      development of metastatic brain tumors in non-small cell lung cancer patients.
      The polymorphisms in TGFB1 rs4803455, rs1800469, and rs1800470 were evaluated by
      polymerase chain reaction-restriction fragment length polymorphism. Odds ratios
      and their corresponding 95% confidence intervals were used to assess the
      influence of TGFB1 rs4803455, rs1800469, and rs1800470 on metastatic brain
      tumors. We found that cases were more likely to have a later disease stage when
      compared with control subjects, without brain metastasis. Individuals carrying
      the TGFB1 rs1800469 TT and CT+TT genotypes had an increased risk of developing
      brain metastasis compared with the rs1800469 CC genotype. Moreover, a significant
      interaction was observed between the rs1800469 polymorphism and disease stage.
      However, no significant association between polymorphisms rs4803455 and rs1800470
      and the risk of developing brain metastasis were observed. We found that the
      TGFB1 rs1800469 polymorphism may be predictive biomarker for the risk of
      developing brain metastasis in non-small cell lung cancer patients. 

PMID- 25966123
TI  - Neuroprotective effect of ketamine on acute spinal cord injury in rats.
AB  - The aim of this study was to investigate the neuroprotective effects of ketamine
      during acute spinal cord injury in rats. Sprague Dawley (SD) rats (N = 70) were
      randomly divided into three groups: sham-operated (N = 10), control (N = 30), and
      treatment (N = 30) groups. The moderate spinal cord injury model was established.
      After injury, the sham-operated group received no drug, the treatment group
      received intraperitoneal ketamine injections, and the control group received
      intraperitoneal normal saline injections. Serum levels of tumor necrosis factor
      alpha (TNF-alpha), interleukin-6 (IL-6), and spinal cord malondialdehyde (MDA)
      were assessed, and nerve cell apoptosis was evaluated in each group at varying
      time points. After spinal cord injury, TNF-alpha, IL-6, and MDA levels, and the
      number of TUNEL-positive cells among 2500 cells significantly increased (P <
      0.05). Further, compared with the control group, the treatment group showed
      significantly lower TNF-alpha, IL-6, and MDA levels, and fewer TUNEL-positive
      cells among 2500 cells at each time point (P < 0.05). Our data indicate that
      ketamine exerts a neuroprotective effect on injured spinal cord. 

PMID- 25966124
TI  - Genetic analysis of QTL for eye cross and eye diameter in common carp (Cyprinus
      carpio L.) using microsatellites and SNPs.
AB  - A group of 107 F1 hybrid common carp was used to construct a linkage map using
      JoinMap 4.0. A total of 4877 microsatellite and single nucleotide polymorphism
      (SNP) markers isolated from a genomic library (978 microsatellite and 3899 SNP
      markers) were assigned to construct the genetic map, which comprised 50 linkage
      groups. The total length of the linkage map for the common carp was 4775.90 cM
      with an average distance between markers of 0.98 cM. Ten quantitative trait loci
      (QTL) were associated with eye diameter, corresponding to 10.5-57.2% of the total
      phenotypic variation. Twenty QTL were related to eye cross, contributing to 10.8
      36.9% of the total phenotypic variation. Two QTL for eye diameter and four QTL
      for eye cross each accounted for more than 20% of the total phenotypic variation
      and were considered to be major QTL. One growth factor related to eye diameter
      was observed on LG10 of the common carp genome, and three growth factors related
      to eye cross were observed on LG10, LG35, and LG44 of the common carp genome. The
      significant positive relationship of eye cross and eye diameter with other
      commercial traits suggests that eye diameter and eye cross can be used to assist
      in indirect selection for many commercial traits, particularly body weight. Thus,
      the growth factor for eye cross may also contribute to the growth of body weight,
      implying that aggregate breeding could have multiple effects. These findings
      provide information for future genetic studies and breeding of common carp. 

PMID- 25966126
TI  - Population genetic structure and historical demography of the ground beetle
      Chlaenius costiger in the Tsinling-Dabashan Mountains of central China.
AB  - Population genetic structure and demographic history of the ground beetle
      Chlaenius costiger (Coleoptera: Carabidae) in the Tsinling-Dabashan Mountains of
      central China were estimated using mitochondrial DNA sequences (Cox1-tRNALeu
      Cox2) of 144 individuals from 16 local populations. The high haplotype diversity
      was accompanied by low nucleotide diversity. Phylogenetic analysis (Bayesian
      inference) of the 43 haplotypes revealed no phylogeographic structure. Analysis
      of molecular variance suggested that most of the variation was attributed to
      within population variation (79.26%). Mantel test results showed a significant
      correlation between the genetic distance and geographical distance of the
      populations with a correlation coefficient equal to 0.216964 (P = 0.0471 < 0.05),
      indicating the presence of isolation by distance. Spatial AMOVA and PERMUT
      analyses showed no phylogeographic structure. Gene flow calculated through the
      number of migrants was high between many pairs of populations. The results of a
      neutrality test, mismatch distribution analyses, and Bayesian skyline plot
      analysis together showed a demographic expansion. The estimated expansion time of
      the whole sampled population was 0.125 million years. The complex topography in
      the Tsinling-Dabashan Mountains area led to the high level of genetic diversity,
      and migratory flight resulted in the high level of gene flow, leading to the lack
      of a phylogeographic structure. 

PMID- 25966125
TI  - Health and production traits in bovine are associated with single nucleotide
      polymorphisms in the NOD2 gene.
AB  - The NOD2 gene plays a fundamental role in initiating the inflammatory and
      subsequent immune response. NOD2 was previously identified as a susceptibility
      locus for inflammatory bowel diseases in humans. In this study, we detected 2
      mutations in exon 12 (A->T, G->A) among 5 cattle breeds (N = 315) and analyzed
      their associations with production traits and genetic resistance against bovine
      mastitis in Chinese Holstein and Chinese Simmental breeds (N = 218). The
      transitions (A->T) at position 114 bp were associated with somatic cell score (P
      < 0.01). The G->A at position 1594 bp plays a critical role in increasing 305-day
      milk yields. In Chinese Holstein and Chinese Simmental breeds, the BB genotype
      may contribute to disease susceptibility. Compared to all genotypic combinations,
      the A, B, and FF genotypes are beneficial not only for reducing somatic cell
      score but also for increasing production. 

PMID- 25966127
TI  - Meta-analytical association between angiotensin-converting enzyme gene
      polymorphisms and sarcoidosis risk.
AB  - Previous reports identified an association between sarcoidosis and an
      insertion/deletion (I/D) polymorphism in angiotensin-converting enzyme. Our meta
      analysis of articles published between March 1996 and June 2013 identified
      studies in the PubMed, EMBASE, and the China National Knowledge Infrastructure
      databases. We examined whether angiotensin-converting enzyme polymorphisms
      influence sarcoidosis susceptibility. The strength of the association between I/D
      polymorphisms and sarcoidosis risk was measured based on the odds ratio and 95%
      confidence interval. Analysis was based on recessive and dominant models. Ethnic
      subgroup analysis from 18 articles (1882 cases and 3066 controls) showed that DD
      homozygote carriers were at a slightly increased risk of sarcoidosis compared
      with II homozygotes and DI heterozygotes (P = 0.03). Comparison of DD plus DI vs
      II revealed no significant association with sarcoidosis in group and ethnic
      subgroup analysis. We found that the I/D polymorphism in the angiotensin
      converting enzyme gene was not associated with a major risk of sarcoidosis. 

PMID- 25966128
TI  - Short Communication: Diversity of TNF-alpha region in Chinese domestic goats.
AB  - Tumor necrosis factor-alpha is a cytokine with a wide range of effects on both
      lymphoid and non-lymphoid cells. In this study, we identified polymorphisms in
      major histocompatibility complex class III gene in the 4th exon and the 3'
      untranslated region of tumor necrosis factor-alpha to evaluate the immunogenetic
      diversity of Chinese south indigenous goat. Three single-nucleotide polymorphisms
      were identified and showed similar frequencies in different except MI loci. These
      data suggest that the high immunodiversity of the tumor necrosis factor-alpha
      region within these breeds can be used for strengthening variety improvement and
      promoting animal husbandry development in Chinese indigenous goats. 

PMID- 25966129
TI  - Therapeutic influence of intraperitoneal injection of Wharton's jelly-derived
      mesenchymal stem cells on oviduct function and fertility in rats with acute and
      chronic salpingitis.
AB  - To study the effect of Wharton's jelly-derived mesenchymal stem cells (WJMSCs) on
      the rat salpingitis model, 50 female Wistar rats were randomly divided into one
      control and five model groups. Mixed bacteria were injected into the oviducts of
      model groups. The treated acute and chronic groups received intraperitoneal
      injections of WJMSCs (1 x 10(6)) once a week for three weeks. Serum inflammation
      factor, collagen fiber content and oviduct-specific glycoprotein (OVGP) levels
      were detected in control, chronic, ex-treatment acute and chronic, and treated
      acute and chronic groups (N = 5 for each group). Pregnancy rate and litter size
      of control, chronic, treated acute and treated chronic groups were compared.
      Serum TNF-alpha and INF-gamma levels increased in ex-treatment acute and chronic
      groups, and restored to normal in the acute treated group but not in the treated
      chronic group. Oviduct collagen fibers did not increase significantly before or
      after treatment in the acute group, but it increased in the ex-treatment chronic
      group and did not improve after treatment. After treatment, OVGP levels restored
      to normal in the acute group but reduced in the ex-treatment and treated chronic
      groups and chronic group. The pregnancy rate and litter size of the treated acute
      group recovered to normal, but in the treated chronic group and chronic model
      group, they decreased significantly. Thus, intraperitoneal injection of WJMSCs
      could recover the function of the oviduct in acute salpingitis rats, but its
      effect on chronic salpingitis was poor. Timely treatment of salpingitis is
      crucial to preserve reproductive function. 

PMID- 25966130
TI  - Case Report: Whole-exome analysis of a child with polycystic kidney disease and
      ventriculomegaly.
AB  - Autosomal recessive polycystic kidney disease (ARPKD) is an inherited ciliopathy
      leading to progressive kidney and liver disease. Biallelic mutations in the PKHD1
      gene underlie this condition. We describe a child with bilaterally enlarged
      cystic kidneys, portal hypertension, and cerebral ventriculomegaly. Molecular
      genetic investigations using whole-exome sequencing and confirmation using Sanger
      sequencing revealed a homozygous pathogenic mutation in PKHD1 underlying the
      clinical phenotype of ARPKD. Whole-exome data analysis was used to search for
      additional rare variants in additional ciliopathy genes that may have contributed
      to the unusual brain phenotype. Aside from a rare hypomorphic allele in MKS1, no
      other pathogenic variants were detected. We conclude that the homozygous
      pathogenic mutation in PKHD1 underlies the ciliopathy phenotype in this patient. 

PMID- 25966131
TI  - Cloning and analysis of the soybean MEKK gene.
AB  - In this paper, homologous cloning methods were used to clone the soybean GmMEKK
      gene, which possesses a high degree of similarity to Arabidopsis thaliana
      AtMEKK1. AtMEKK1 is formed by 595 amino acids, and its secondary structure is
      formed by 38 irregular curls, 24 alpha helix, 14 beta, with S-TKc domain,
      transmembrane domain and does not have membrane spanning domain and signal
      peptide. GmMEKK-GFP subcellular localization fusion and prokaryotic expression
      vectors were generated and it was revealed that GmMEKK encodes a highly conserved
      66.8-kDa nuclear protein that is expressed in soybean roots, stem floral pieces,
      and leaves. A real-time quantitative PCR analysis of GmMEKK under different
      abiotic stresses revealed that the expression level of GmMEKK increased under
      drought and low phosphorus and nitrogen conditions. Taken together, these data
      suggest that GmMEKK may play an important role in the soybean abiotic stress
      response. 

PMID- 25966132
TI  - Clinical value of concurrent radiochemotherapy in cervical cancer and comparison
      of ultrasonography findings before and after radiochemotherapy.
AB  - Herein, we investigated the clinical value of concurrent radiochemotherapy for
      patients with advanced cervical cancer and its effects on adverse clinical
      symptoms. Forty patients with cervical cancer were recruited from January 2011 to
      January 2014 for this study. Participants were randomly allocated into a test or
      control group, with 20 patients in each group. Patients in the test group were
      treated with concurrent radiochemotherapy, whereas patients in the control group
      received only traditional radiotherapy. At the end of the observation period,
      clinical efficacy in the two groups was compared. Patients were followed up for 2
      years, and the rates of recurrence, survival, and complications were compared;
      ultrasonographic findings before and after radiotherapy were also correlated.
      Patients in the test group who received concurrent radiochemotherapy showed
      significantly higher clinical efficacy than the control group at the end of
      treatment cycles. After 2 years of follow-up, the rates of recurrence, mortality,
      and complications were all significantly lower in the test group than in the
      control group (P < 0.05). Comparison of ultrasonographic findings before and
      after radiochemotherapy showed that the size of the tumor was significantly
      smaller in patients after concurrent radiochemotherapy. Compared with traditional
      radiotherapy, concurrent radiochemotherapy significantly improved clinical
      outcomes in patients with advanced cervical cancer. Concurrent radiochemotherapy
      also enhanced the rate of survival and decreased the rate of relapse, with
      enhanced clinical safety and no significant side effects. Thus, concurrent
      radiochemotherapy can be more broadly applied in the treatment of advanced
      cervical cancer. 

PMID- 25966133
TI  - DNMT3A -448A>G polymorphism and cancer risk: a meta-analysis.
AB  - Cancer is a major public health problem worldwide that involves complex processes
      and factors. For instance, methylation is important in tumorigenesis. DNA
      (cytosine-5)-methyltransferase 3A (DNMT3A) is the main de novo methyltransferase
      implicated in this process. In DNMT3A, the -448A>G polymorphism is associated
      with cancer; however, the results of various studies have been conflicting. To
      clarify the role of DNMT3A polymorphisms in cancer, we conducted a meta-analysis
      of 2014 cases and 3089 control subjects. Odds ratios with 95% confidence
      intervals were estimated to evaluate the association between the DNMT3A -448A>G
      polymorphism and cancer risk. The results showed that DNMT3A may be a protective
      factor against all cancer types and colorectal cancer groups. Further studies
      should be conducted including different ethnicities and large population sizes to
      generate a comprehensive conclusion. 

PMID- 25966134
TI  - Effects of silver nanoparticles and gold nanoparticles on IL-2, IL-6, and TNF
      alpha production via MAPK pathway in leukemic cell lines.
AB  - Silver nanopaticles (AgNPs) and gold nanoparticles (AuNPs) have various
      applications in medical healthcare and various biological properties such as anti
      inflammation, anti-cancer, and anti-angiogenesis. In this study, we investigated
      the effect of AgNPs and AuNPs on cytokine production via the mitogen-activated
      protein kinase pathway in leukemic cell lines (T-lymphocytic Jurkat and monocytic
      U937 cells). We found that both AgNPs and AuNPs inhibited cell proliferation of
      leukemic cell lines. AgNPs inhibited TNF-alpha, while AuNPs inhibited interleukin
      2 production in Jurkat cells, in which inhibition of cytokines is involved in the
      extracellular-signal regulated protein kinase but not the c-Jun N-terminal kinase
      pathway. In U937 cells, AuNPs inhibited interleukin-6 but stimulated TNF-alpha
      production in a concentration-dependent manner through the c-Jun N-terminal
      kinase but not the extracellular-signal regulated protein kinase pathway. Our
      study showed that each leukemic cell line treated with nanoparticles exhibited a
      distinct signaling pathway response to inhibit or stimulate cytokine production,
      leading to anti-cell proliferation. The effects of AgNPs and AuNPs on leukemic
      cell lines may have a significant impact on leukemia treatment in the future. 

PMID- 25966135
TI  - Novel polymorphisms of the PRKAG2 gene and their association with body
      measurement and meat quality traits in Qinchuan cattle.
AB  - Body measurement and meat quality traits play important roles in the evaluation
      of productivity and economy in cattle, which are influenced by genes and
      environmental factors. PRKAG2, which encodes the gamma2 regulatory subunit of
      AMPK, is associated with key metabolic pathways in muscle. We detected bovine
      PRKAG2 gene polymorphisms and analyzed their associations with body measurement
      and meat quality traits of cattle. DNA samples were taken from 578 Qinchuan
      cattle aged 18-24 months. DNA sequencing, polymerase chain reaction-restriction
      fragment length polymorphism, and time-of-flight mass spectrometry were used to
      detect PRKAG2 single nucleotide polymorphisms (SNPs). Sequence analysis revealed
      three SNPs in exon 3 (g.95925G>A, g.95973G>C, and g.95992A>G) and one g.96058T>C
      mutation in intron 3. g.95973G>C, g.95992A>G, and g.96058T>C each showed 3
      genotypes: GG, GC, and CC; AA, AG, and GG; and TT, TC, and CC, respectively. In
      contrast, g.95925G>A only showed 2 genotypes, GG and GA. Analysis showed that
      g.95925G>A had no effects on body measurement and meat quality traits, whereas
      the other 3 polymorphisms were significantly associated with some of the body
      measurement and meat quality traits in the Qinchuan cattle population. It is
      inferred that the PRKAG2 gene can be used for marker-assisted selection to
      improve the body measurement and meat quality traits in the Qinchuan cattle
      population. 

PMID- 25966136
TI  - Evaluation of the function status of the ulnar nerve in carpal tunnel syndrome.
AB  - Many carpal tunnel syndrome (CTS) patients have symptoms in both the median and
      ulnar digits more frequently than in the median digits alone. This is possibly
      because of close anatomical contiguity of the carpal tunnel and Guyon's canal,
      and the high pressure may also affect the latter, causing indirect compression of
      ulnar nerve fibers. Thus, we evaluated the functional status of the ulnar nerve
      in patients with CTS in order to investigate the relationship between ulnar nerve
      impairment and sensory symptoms of the ulnar territory. Electrophysiological
      studies were conducted in CTS patients and healthy controls. CTS patients were
      divided into the mild/moderate group and severe group; they were further divided
      into the symptomatic and asymptomatic subgroups according to the sensory symptom
      of the fifth digit region. The findings suggest that CTS patients could have
      coexisting ulnar nerve wrist entrapments that might exacerbate the severity of
      CTS. Sensory impairment in the ulnar territory was observed more frequently in
      the mild/moderate stage of CTS, which is associated with ulnar nerve involvement.
      These findings also suggest that damage to the ulnar nerve fibers caused by
      compression forces in Guyon's canal may underlie the ulnar spread of symptoms in
      CTS. 

PMID- 25966137
TI  - Rapid sedation induced by fentanyl combined with propofol via an intrathecal
      chemotherapy injection for leukemia in children.
AB  - This study explored the sedative and analgesic effects of fentanyl combined with
      propofol via an intrathecal chemotherapy injection for acute leukemia (acute
      lymphocytic leukemia or acute myelocytic leukemia) among children, to relieve
      pain and difficulty during intrathecal injection, improve treatment compliance,
      increase the success rate of single puncture, and reduce procedure failure, with
      the aim of developing a painless procedure for children with acute leukemia.
      Fifty person-times received fentanyl combined with propofol via an intrathecal
      chemotherapy injection among the hospitalized children with leukemia. The
      patients' cooperation with the procedure, response to the medication, dosages of
      fentanyl and propofol, reaction to the procedures, wake-up time, and changes in
      oxygen saturation (SpO2), heart rate (HR), respiration, and blood pressure (BP)
      before, during, and after the procedures were observed. The doctors who performed
      the procedures assessed the quality of sedation and analgesia. In the treatment
      group, the patients were quiet during the lumbar puncture and intrathecal
      injection, showing good sedation and analgesia. HR and respiration decreased
      slightly. There were no changes in SpO2 and BP. No obvious respiratory depression
      occurred with proper dosages. Only a few patients showed stertorous respiration,
      which stopped soon after the procedures. In the control group, the patients were
      agitated, crying, and not cooperative before and during the procedures, which
      made the procedures very difficult. During intrathecal injection, pain obviously
      reduced and the success rate of single lumbar puncture increased. It is safe and
      effective to apply fentanyl combined with propofol for sedation and analgesia. 

PMID- 25966138
TI  - Feasibility of comfortable and secure intubation achieved with the Disposcope
      endoscope or Macintosh laryngoscope for patients in whom glottis viewing is
      difficult.
AB  - We aimed to study the feasibility of a comfortable and secure intubation achieved
      with the Disposcope endoscope or Macintosh laryngoscope when glottis viewing is
      difficult. Forty adults scheduled for elective surgery under general anesthesia,
      in whom glottis viewing was difficult with the Macintosh laryngoscope (classified
      as Cormack-Lehane Grade III or IV), were randomized into 2 groups (N = 20 each):
      Disposcope endoscope (Group D) and Macintosh laryngoscope (Group M). We recorded
      the successful glottis viewing rate; intubation time; successful intubation rate;
      incidence of systolic blood pressure (SBP) >=140 mmHg and heart rate (HR) >=90
      bpm from the beginning of intubation to 5 min after intubation; and postoperative
      sore throat and hoarseness. Successful glottis viewing rate and successful first
      intubation rate were higher in Group D than in Group M (P < 0.05); the number of
      intubations taking >3 min and with SBP >=140 mmHg and HR >=90 bpm were less in
      Group D (P < 0.05). The visual analogue scale of postoperative sore throat 1 day
      after extubation was higher in Group M than in Group D (P < 0.05). No significant
      differences were found in other indices (P > 0.05). Better stability of
      hemodynamics, less intubation time, higher successful first intubation rate, and
      fewer incidences of postoperative sore throat were achieved in Group D than in
      Group M. Thus, comfortable and secure intubation can be achieved using the
      Disposcope endoscope in patients in whom glottis viewing is difficult. 

PMID- 25966139
TI  - A comparative study of stress-related gene expression under single stress and
      intercross stress in rice.
AB  - Plant hormones play important roles in the crosstalk between biotic and abiotic
      stresses in rice throughout its entire growth period. However, these interactions
      are not completely understood. In this study, the physiological performance of
      rice seedlings under a single stress and a sequential combination of various
      stresses (intercross stress) was determined. We found that catalase, superoxide
      dismutase, and peroxidase activities and malondialdehyde were highly regulated by
      intercross stresses. Furthermore, the expression levels of pathogenesis-related
      genes and drought stress-related genes under various treatments were analyzed. We
      demonstrated that under drought-disease intercross stress, the expression levels
      of the PR4, PAL, and Cht-1 genes were significantly upregulated, while under salt
      disease intercross stress, the expression levels of the PR1a, PBZ1, Gns1, and Cht
      1 genes underwent significant changes. Regardless of the type of intercross
      stress, the expression of LOX-RLL was significantly affected. We also showed that
      the expression of drought stress-related genes OsSKIPa, OsNADPH1, JRC0594, and
      OsGL1-2 was significantly regulated, suggesting that these genes play important
      roles in the interaction between biotic and abiotic stresses. We, therefore,
      conclude that the interactions between various types of biotic and abiotic
      stresses vary in a complex pattern and would require further in-depth
      investigation. 

PMID- 25966140
TI  - Attenuated mRNA expression of lipid metabolism genes in primary hepatocytes
      following lipopolysaccharide treatment in dairy cows.
AB  - The influence of ruminal acidosis on ruminal microbiology and metabolite
      production has received considerable attention, but little is known regarding the
      systemic manifestations that arise from ruminal acidosis. Lipopolysaccharide
      (LPS) is released in the gastrointestinal tract upon ingestion of high-grain or
      high-fat diets, and it has been implicated in the etiology of multiple energy-
      and lipid-related metabolic disturbances in ruminants. The liver plays a crucial
      role in the acute phase response to intruding pathogens. The effect of blood LPS
      in subacute ruminal acidosis on lipid metabolism in the liver has not been
      established. In this study, cell cultures were photographed using an inverted
      microscope. We observed that hepatocytes changed their morphologies from
      irregular triangle to circular (contraction) shapes; the number of contracted
      cells increased with the increasing LPS doses. This suggests that LPS can promote
      cell contraction and take off the wall, ultimately leading to cell apoptosis.
      With changes in LPS exposure, hepatocyte number also changes. We explored lipid
      metabolism in the liver using quantitative reverse transcription-polymerase chain
      reaction to detect the expression of key lipid metabolism enzymes in hepatocytes.
      We found that Toll-like receptor 4 signaling pathway mediated by LPS could
      attenuate mRNA expression of fatty acid synthesis genes and increase the
      expression of fatty acid transport genes in primary hepatocytes following LPS
      treatment in dairy cows. 

PMID- 25966141
TI  - Expression and variation of Myf5 and MyoD1 genes in different tissues of
      Wuzhishan pigs.
AB  - The myogenic regulatory factor (MRF) family includes Myf5, MyoD1, Myf4, and Mfy6
      genes. This experiment assessed the variation of Myf5 and MyoD1 genes from birth
      to maturity (30, 210, and 360 days) in the back muscle tissue of Wuzhishan pigs
      (WZSP), and the expression of Myf5 and MyoD1 mRNA in the heart, liver, lung,
      spleen, kidney, muscle, stomach, and intestine tissues were also examined. The
      results indicate that the expression level of mRNA for Myf5 and MyoD1 genes in
      the back muscle tissue is directly proportional to age (P < 0.05). Furthermore,
      of the eight adult pig tissue types that were tested, the expression of Myf5 and
      MyoD1 was highest in the muscle tissue. 

PMID- 25966142
TI  - Adeno-associated virus-mediated BMP-7 and SOX9 in vitro co-transfection of human
      degenerative intervertebral disc cells.
AB  - Bone morphogenetic protein-7 (BMP-7) and SOX9 are important transcription factors
      in chondrogenesis. In this study, we examined the biological function of the
      adeno-associated virus (AAV)-mediated BMP-7 and SOX9 double gene in vitro co
      transfection of nucleus pulposus cells of human degenerative intervertebral disc.
      Human intervertebral disc nucleus pulposus cells were cultured in vitro and
      subcultured for 5 generations. Using rAAV-BMP-7 and rAAV-SOX9 AAV2-type AAV
      viruses, the cells were divided into 4 groups: blank normal, BMP-7 transfection,
      SOX9 transfection, and BMP-7 and SOX9 co-transfection. After 48 h, expression of
      type II collagen and its mRNA in nucleus pulposus cells was determined. The
      expression of type II collagen in BMP-7 transfection, SOX9 transfection, and co
      transfection groups was up-regulated to varying degrees compared to the blank
      control group. The type II collagen mRNA level expression in the co-transfection
      group was significantly higher than in other groups (P < 0.05). AAV-mediated BMP
      7 and SOX9 in vitro co-transfection can promote the synthesis of type II collagen
      in nucleus pulposus cells in the human degenerative intervertebral disc. Double
      gene therapy has a synergistic effect in the treatment of intervertebral disc
      degeneration. 

PMID- 25966143
TI  - Relationship between genetic polymorphisms in MCP-1, CCR-2, and non-small-cell
      lung cancer in the Han nationality of Northern China.
AB  - Lung cancer is a common malignant tumor worldwide and is now the leading cause of
      cancer-related deaths. Monocyte chemoattractant protein 1 (MCP-1) and its
      receptor chemokine receptor 2 (CCR-2) are important chemokines. We examined the
      polymorphisms of 338 unrelated patients with non-small cell lung carcinoma
      (NSCLC) and 200 unrelated healthy controls of Han nationality in Northern China
      using polymerase chain reaction-restriction fragment length polymorphism. We
      found a significant increase in the frequency of the MCP-1 AA genotype [0.293 vs
      0.195, odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.13-2.60] and a
      significant decrease in the frequency of the GG genotype (0.290 vs 0.41, OR =
      0.64, 95%CI = 0.47-0.87) in NSCLC patients compared to controls. The frequencies
      of AA-ww (0.151 vs 0.090, P = 0.041, OR = 1.80, 95%CI = 1.33-2.43) and AA-wm
      (0.136 vs 0.080, P = 0.049, OR = 1.81, 95%CI = 1.01-3.27) were higher in lung
      cancer patients than in healthy controls; the frequency of GG-wm (0.121 vs 0.190,
      P = 0.030, OR = 0.60, 95%CI = 0.38-0.95) was lower in lung cancer patients than
      in healthy controls. Based on these results, the polymorphism in MCP-1 may be
      correlated with the development of NSCLC in the Han nationality of Northern
      China. However, the polymorphism in CCR-2 is not involved in NSCLC. 

PMID- 25966144
TI  - Investigating the prevention of hospital-acquired infection through standardized
      teaching ward rounds in clinical nursing.
AB  - This study aimed to explore the effect of standardized teaching ward rounds in
      clinical nursing on preventing hospital-acquired infection. The experimental
      group comprised 120 nursing students from our hospital selected between June 2010
      and June 2012. The control group consisted of 120 nursing students selected from
      May 2008 to May 2010. Traditional teaching ward rounds for nursing education were
      carried out with the control group, while a standardized teaching ward round was
      carried out with the experimental group. The comprehensive application of nursing
      abilities and skills, the mastering of situational infection knowledge, and
      patient satisfaction were compared between the two groups. The applied knowledge
      of nursing procedures and the pass rate on comprehensive skill tests were
      significantly higher in the experimental group than in the control group (P <
      0.05). The rate of mastery of sterilization and hygiene procedures was also
      higher in the experimental group than in the control group (P < 0.05). The
      patient satisfaction rate with infection control procedures in the experimental
      group time period was 98.09%, which was significantly higher than patient
      satisfaction in the control group time period (93.05%, P < 0.05). Standardized
      teaching ward rounds for nursing education expanded the knowledge of the nursing
      staff in controlling hospital-acquired infection and enhanced the ability of
      comprehensive application and awareness of infection control procedures. 

PMID- 25966145
TI  - Transthoracic closure of atrial septal defect and ventricular septal defect
      without cardiopulmonary bypass.
AB  - The minimally invasive surgical transthoracic occlusion of an atrial septal
      defect (ASD) or a ventricular septal defect (VSD) is an increasingly widespread
      alternative treatment for congenital heart disease. The aim of this study is to
      summarize our clinical experience with minimally invasive surgical transthoracic
      occlusion of ASD and VSD without cardiopulmonary bypass (CPB). Between April 2011
      and October 2012, 27 patients with ASD and 95 patients with VSD (78 men and 44
      women) were considered for minimally invasive surgical transthoracic occlusion
      without CPB. A small infrasternal incision (2.0-4.0 cm) was made under general
      anesthesia, under transesophageal echocardiography (TEE) guidance; the ASD and
      VSD were closed by using an appropriate occluder; and TEE was performed
      simultaneously to demonstrate the position of the device, any residual shunting,
      or encroachment on the atrioventricular valve, coronary sinus, or aortic valve.
      Successful transthoracic occlusion was performed in all 122 patients without
      complications. No complications such as third-degree atrioventricular block and
      residual shunting occurred after the procedures. The ventilation time was 2.2 +/-
      1.2 h, and the average length of hospital stay was 4.7 +/- 1.7 days. All patients
      received aspirin at 3 mg.kg(-1).day(-1) (maximum 100 mg/day) 24 h after the
      procedure. Minimally invasive surgical transthoracic occlusion without CPB is a
      new treatment that has many advantages such as causing little trauma, promoting
      quick recovery, having less complications, and avoiding radiation damage.
      However, the appropriate selection of patients is still key to improving the
      success rate of the operation. 

PMID- 25966146
TI  - T174M polymorphism in the angiotensinogen gene and risk of myocardial infarction:
      a meta-analysis.
AB  - Numerous studies have evaluated the association between the T174M polymorphism in
      the angiotensinogen (AGT) gene and myocardial infarction (MI) risk. However, the
      specific association remains controversial because of small sample sizes and
      varied study designs among different studies. We performed a meta-analysis to
      assess this correlation. A comprehensive search was conducted to identify all
      published articles regarding the association between the AGT gene T174M
      polymorphism and MI risk from different databases. Pooled odds ratios (ORs) with
      95% confidence intervals (CIs) were calculated, and heterogeneity and publication
      bias were assessed. A total of 1032 patients with lung cancer and 1286 controls
      from 6 comparative studies were included in this meta-analysis. The results
      revealed a significant association between the AGT gene T174M polymorphism and MI
      risk (MM vs TT: OR = 2.87, 95%CI = 1.71-4.83; dominant model: OR = 1.57, 95%CI =
      1.10-2.25; recessive model: OR = 0.41, 95%CI = 0.25-0.66). In subgroup analysis
      by nationality, we observed a significant association between the AGT gene T174M
      polymorphism and susceptibility to MI in both Caucasian and Asian populations. In
      conclusion, the T174M polymorphism in the AGT gene may be related to an increased
      risk of MI. Further larger studies are needed to confirm these conclusions. 

PMID- 25966147
TI  - Decreased levels of soluble receptor for advanced glycation end-products in
      aortic valve calcification patients.
AB  - The soluble receptor for advanced glycation end-products (sRAGE) shows a close
      relationship with atherosclerosis. The goal of this study was to compare the
      levels of sRAGE in patients with and without aortic valve calcification and to
      investigate the relationship between them. After transthoracic echocardiographic
      examination, 120 male patients with aortic valve calcification and 120 age
      matched male controls without aortic valve calcification were included in our
      study. sRAGE levels were compared between groups. The prevalence of diabetes
      mellitus and coronary artery disease were significantly higher in the aortic
      valve calcification group than in the control group (63.3 versus 45%, P = 0.01,
      and 65 versus 51.7%, P < 0.01, respectively). The levels of sRAGE were lower in
      the aortic valve calcification group than in the control group (203.8 +/- 34.6
      versus 324.7 +/- 41.6 pg/mL, P < 0.01). In multivariate analysis, age, coronary
      artery disease, and sRAGE levels were independent predictors of aortic valve
      calcification. Our study demonstrates that sRAGE, which was proven to be a
      potential marker of atherosclerosis, might have a role in the development of
      aortic valve calcification. 

PMID- 25966148
TI  - Clinical value of ultrasound-guided percutaneous biopsy of pulmonary lesions.
AB  - The purpose of this study was to evaluate the applica-bility of ultrasound-guided
      percutaneous biopsy for the diagnosis and differentiation of various pulmonary
      lesions in a Chinese population. A total of 338 pulmonary lesions were biopsied
      with 18-gauge cutting needles, guided by ultrasound, and sent for
      histopathological analy-sis. The ultrasonographic characteristics of these
      lesions, procedure complications, and histopathological diagnoses were analyzed.
      Suffi-cient specimen for histopathologic analysis was obtained in 95.64%
      (351/367), and mild complications occurred in 2.72% (10/367) of the patients.
      Accurate diagnosis was obtained in 94.03% (315/335) of the patients; 16 were lost
      to follow-up. Using the combination of shape and echogenicity to distinguish
      benign vs malignant lesions, diagnos-tic sensitivity and specificity were 57.39
      and 95.65%, respectively. No significant difference was found between malignant
      and benign lesions in blood flow signals. Ultrasound-guided core biopsy is
      valuable for the diagnosis, management, and prognosis of unknown pulmonary
      lesions. Shape and echogenicity on ultrasonography correlate well with histo
      pathology and provide useful information for distinguishing between benign and
      malignant lesions. On the contrary, color Doppler is of little value for this
      purpose. 

PMID- 25966149
TI  - Analysis of tacrolimus blood concentrations in renal transplant patients.
AB  - This study aimed to 1) analyze the results of tacrolimus blood concentration
      monitored in patients after renal transplantation, 2) observe and establish an
      optimal therapeutic window for patients, and 3) provide evidence for the clinical
      and rational use of drugs. Tacrolimus blood concentration was determined by
      enzyme-linked immunosorbent assay. A total of 1824 cases were obtained from the
      monitoring of 74 patients after renal transplantation. These cases were then
      retrospectively analyzed. Over time, the mean whole blood tacrolimus trough
      concentration after transplantation gradually decreased. This result suggests
      that the optimal therapeutic windows for patients with renal transplants are as
      follows: 5 to 20 MUg/L at 1 month after surgery; 5 to 15 MUg/L at 1-3 months
      after surgery; 4 to 12 MUg/L at 3-6 months after surgery; 4 to 10 MUg/L at 6-12
      months after surgery; and 3 to 8 MUg/L at >12 months after surgery. The
      absorption of tacrolimus is highly variable. Therefore, tacrolimus concentration
      in the blood and the recommended clinical therapeutic window should be routinely
      monitored to adjust the treatment regimen and reduce adverse reactions. In this
      way, treatment can be optimized. 

PMID- 25966150
TI  - Preoperative computed tomography-guided hook-wire positioning of pulmonary
      nodules.
AB  - This study aimed to analyze the clinical application value of computed tomography
      (CT)-guided hook-wire positioning before thoracoscopic surgery. Eighty-four
      patients who had received a thoracoscopic wedge resection of pulmonary nodules
      between January and December 2013 were selected. Group A consisted of 38 cases
      where the hook-wire positioning technique was not used, and the positioning
      approaches were intraoperative observation and palpation. Group B consisted of 46
      cases where the hook-wire positioning technique was used. The diameter of each
      nodule was less than 2 cm, and all patients underwent the operation within 2 h of
      invasive positioning. The evaluation indexes included positioning success rate,
      positioning-related complications, and rate of conversion to thoracotomy. In
      Group A, nine patients (23.68%) underwent conversion to thoracotomy; in Group B,
      three patients (6.52%) did. This difference was statistically significant (P <
      0.05). The average operation duration was 118 +/- 21 min in Group A and 53 +/- 18
      min in Group B. The difference between both groups was statistically significant
      (P < 0.05). The average length of hospital stay of patients who underwent
      conversion to thoracotomy was 8.7 +/- 2.2 days, and of patients who underwent
      thoracoscopic pulmonary wedge resection was 4.5 +/- 1.6 days. This difference was
      statistically significant (P < 0.05). Therefore, CT-guided hook-wire positioning
      of pulmonary nodules before thoracoscopic surgery has clinical application value.
      It helps to accurately locate the pulmonary nodules, effectively lowers the rate
      of conversion to thoracotomy, and reduces the operation duration. 

PMID- 25966151
TI  - Analysis of ROP signaling in the leaf epidermis of mutant tomato with low-energy
      ion beam.
AB  - The importance of the ROP small GTPase signaling pathway in the regulation of
      cellular polarity growth in eukaryotes has been thoroughly studied. In this
      study, we examined the LeROP small GTPase (related to Arabidopsis thaliana genome
      LeROP GTPase in tomato) signaling of cell polarity growth in the mutant (M-1)
      tomato. Interestingly, we detected expansive growth of epidermis cells in M-1, in
      which the leaves appeared slightly lobed shaped. However, we observed jigsaw
      puzzle shaped and deeply lobed shaped leaves in wild-type leaf epidermis cells.
      The t-test showed significant difference (P < 0.05). Based on previous studies of
      the AtROP gene in Arabidopsis leaf epidermis cells, we hypothesized that the
      growth of mutant M-1 tomato leaf epidermis cell is related to AtROP gene signal
      transmission. The results of reverse transcription-polymerase chain reaction
      showed the expression of LeROP2, LeROP4, and LeROP7 in M-1 mutants were stronger
      than in wild-type cells. At the flowering stage, LeROP2 GTPase showed no
      expression in wild-type cells, but was expressed in mutant cells. This study
      revealed a link between the low-energy ion beam and the ROP GTPase signaling
      pathway in tomato. In addition, the ROP gene changes analyzed suggest a new
      mechanism for mutations following low-energy ion beam implantation. 

PMID- 25966152
TI  - tRNALeu intron (UAA) of Ficus carica L.: genetic diversity and evolutionary
      patterns.
AB  - Cytoplasmic chloroplast DNA was explored to establish genetic relationships among
      Ficus carica cultivars and elucidate the molecular evolution of the species. The
      results suggest the occurrence of haplotype and nucleotide diversity. Conserved
      group I intron sequence motifs were detected and showed a common secondary
      structure, despite the presence of some mutations on their sequences. The
      neighbor-joining dendrogram showed a continuous diversity that characterizes
      local resources. The maximum parsimony tree, with an RI index of 0.507, indicated
      minimal homoplasy within the data set. Furthermore, our results demonstrate that
      the trnL intron is the seat of numerous substitutions. Herein, new insight on the
      mechanism involved in the evolution of the trnL intron in the fig is presented.
      From the study, it appears that there is an explicit rejection of the null
      hypothesis in F. carica. A scenario of positive selection and recent expansion of
      F. carica genotypes across Tunisia seems to be retained. 

PMID- 25966153
TI  - Clinical observational study of conformal radiotherapy combined with topotecan
      chemotherapy in patients with platinum-resistant recurrent ovarian cancer.
AB  - This retrospective study aimed to observe the cura-tive effect and adverse
      reactions of three-dimensional conformal radiotherapy combined with topotecan
      chemotherapy in patients with platinum-resistant recurrent epithelial ovarian
      carcinoma. The chemoradiotherapy group (N = 22) received 15 mv X-rays with 1.8 to
      2.0 Gy/f/d radiation, 5 times per week. The total dose was 45 to 65 Gy; the
      median dose was 52.5 Gy. Topotecan chemotherapy (2.0 mg/m(2)) was administered
      after the first week of radiotherapy on days 1, 8, and 15; it was repeated every
      28 days. The only che-motherapy group (N = 20) received topotecan chemotherapy
      (4.0 mg/m(2)) in the first week, and the dose was administered on days 1, 8, and
      15; it was repeated every 28 days. The median follow-up times were 18.5 months (2
      to 37.7) and 10.8 months (1.5 to 29.6) in the chemoradiotherapy and in the only
      chemotherapy groups, respectively. The total response rates were 42.1% (8/19) and
      11.1% (2/18), respectively. The clinical benefit rates were 68.4% (13/19) and
      22.2% (4/18), respectively, with significant difference (P < 0.05). The median
      disease progression-free periods were 9.8 and 6.6 months, respectively, with
      significant difference (P < 0.001). The median survival times were 19.7 and 12.5
      months, respective-ly, with significant difference (P < 0.05). The degrees of
      digestive tract reaction rates were 26.3% (5/19) and 16.7% (3/18), whereas the
      hematology toxicity rates were 21.1% (4/19) and 22.2% (4/18), respectively, with
      no significant difference (P > 0.05). As three-dimensional conformal radiotherapy
      combined with topotecan che-motherapy had good curative effect on platinum
      resistant recurrent epithelial ovarian cancer, with mild adverse reactions, this
      tech-nique can be used as a remedial measure. 

PMID- 25966154
TI  - Polymorphisms in the SIRT5 gene and their association with body measurement and
      ultrasound traits in Qinchuan cattle.
AB  - Silent information regulator 5 (SIRT5), a member of the Sirtuin family class III
      nicotinamide adenine dinucleotide-dependent protein deacetylases, plays an
      important role in metabolic and aging processes in mammals. We identified 4
      single-nucleotide polymorphisms (SNPs) (G22010A, G22052A, G22119T, and G22245C)
      in the 3' untranslated regions of the SIRT5 gene from 572 Qinchuan cattle by
      sequencing and investigating their association with growth and ultrasound traits.
      The frequencies of genotype GG and allele G were high at the 4 SNPs. Based on the
      X(2) test, the genotypic distributions of the 4 SNPs were not in Hardy-Weinberg
      equilibrium (P < 0.05 or P < 0.01). Association analysis of individual SNPs and
      haplotype combinations revealed that the 4 loci were significantly associated
      with some body measurement and ultrasound traits in Qinchuan cattle, and the H1H5
      (AG-GA-GG-GG) diplotypes had better performance than other combinations in
      Qinchuan cattle. Our results demonstrate that SIRT5 may be a candidate for marker
      assisted selection in future breeding programs for Qinchuan cattle. 

PMID- 25966155
TI  - QTL mapping of forage yield and forage yield component traits in Sorghum bicolor
      x S. sudanense.
AB  - The sorghum-sudangrass hybrid (Sorghum bicolor x S. sudanense) is an important
      forage crop. However, little is known about the genetic mechanisms related to
      forage yield and the 4 forage yield component traits in this forage crop. In this
      study, a linkage map was constructed with 124 assigned SSR markers using an F2
      mapping population derived from the crossing of sorghum Tx623A and sudangrass Sa.
      Nine quantitative trait loci (QTLs) were detected for forage yield and the 4
      forage yield component traits using inclusive composite interval mapping. Five
      fresh weight QTLs were identified and contributed >50% of the total phenotypic
      variance. Of these QTLs, all showed additive and dominant effects, but most
      exhibited mainly dominant effects. These results will provide useful information
      for improvements in sorghum-sudangrass hybrid breeding. 

PMID- 25966156
TI  - Effect of different time phases of radionuclide hepatobiliary scintigraphy on the
      differential diagnosis of congenital biliary atresia.
AB  - To investigate the value and essentiality of 6- and 24-h delay hepatobiliary
      scintigraphy in the differential diagnosis of biliary atresia (BA), we
      retrospectively analyzed 197 infants (121 boys/76 girls; age range, 3-205 days;
      average age, 63.9 days) admitted to Jiangxi Children's Hospital for persistent
      jaundice (> 2 weeks), hepatosplenomegaly, and abnormal liver function. After
      receiving anti-inflammatory treatment and cholagogic pre-treatment for 7-10 days
      without a clear diagnosis, the children underwent 99mTc-labeled
      diethylacetanilide-iminodiacetic acid hepatobiliary scintigraphy. BA and infant
      hepatitis syndrome were diagnosed in 107 and 90 infants, respectively after
      laparoscopic cholangiography, surgical pathology, or 6-month clinical follow-up.
      The diagnostic efficiencies of hepatobiliary scintigraphy for BA were evaluated
      within 50 min and at 6 and 24 h. The areas under the receiver operating
      characteristic curves within 50 min, at 6 and 24 h were 0.696, 0.829 , and 0.779
      , suggesting poor diagnostic value within 50 min, but improvement at 6 and 24 h.
      The compliance rate of 6- and 24-h imaging for BA diagnosis was 89.34% (176/197;
      paired chi-square test Kappa value, 0.77; P > 0.05), signifying high consistency.
      The diagnostic efficiency values of 6-/24-h imaging for BA diagnosis were
      sensitivity (90.65/89.72%), specificity (74.44/78.89%), accuracy (83.25/84.77%),
      positive and negative predictive values (80.83/83.48% and 87.01/86.59%), with no
      significant difference (P > 0.05). To provide optimal treatment in early BA, the-
      6-h hepatobiliary scintigraphy had practical value, especially when combined with
      tomographic or dynamic imaging; 24-h delay imaging was deemed unnecessary because
      it was not significantly superior. 

PMID- 25966157
TI  - Association between MTHFR 677C/T polymorphism and psoriasis risk: a meta
      analysis.
AB  - Previous studies investigating the association between methylenetetrahydrofolate
      reductase (MTHFR) 677C/T polymorphisms and psoriasis risk have reported
      inconsistent results. The present meta-analysis aimed to comprehensively evaluate
      the association between MTHFR 677C/T polymorphism and psoriasis risk. The studies
      regarding the association between MTHFR 677C/T polymorphism and psoriasis risk
      were retrieved from the PubMed, Embase, Web of Science, Chinese National
      Knowledge Infrastructure, and Chinese Biomedical databases. Data were extracted
      and statistical analysis was performed with the program STATA 12.0. A total of
      seven studies involving 1290 psoriasis cases and 1068 healthy controls were
      retrieved. Combined analysis showed that there was no significant difference in
      MTHFR 677C/T genotype distribution between psoriasis and control subjects in the
      comparisons C vs T, CC vs CT + TT, CC + CT vs TT, CC vs TT, and CC vs CT
      [respectively: odds ratio (OR) = 0.98, 95% confidence interval (CI) = 0.76-1.26,
      P = 0.882; OR = 1.11, 95%CI = 0.81-1.51, P = 0.526; OR = 0.79, 95%CI = 0.53-1.19,
      P = 0.261; OR = 0.88, 95%CI = 0.51-1.52, P = 0.648; OR = 1.19, 95%CI = 0.90-1.58,
      P = 0.217]. Subgroup analysis by ethnicity also showed no significant association
      between MTHFR 677C/T polymorphism and psoriasis risk in both Asian and Caucasian
      populations. In conclusion, this meta-analysis indicates that MTHFR 677C/T
      polymorphism may not be associated with psoriasis risk.

PMID- 25966159
TI  - Serum immunoglobulin E level and its impact on the pregnancy outcome associated
      with fetal growth restriction: a prospective cohort study.
AB  - We evaluated the relationship between total serum immunoglobulin E (IgE) levels
      and pregnancy outcome in a prospective cohort study focusing on fetal growth
      restriction (FGR). Sixty women with FGR and twenty with normal singleton
      pregnancy were enrolled during their third trimester. Infants were followed up
      for 6 months. Blood samples were obtained from pregnant women during the third
      trimester; cord blood samples were also taken. Six months after birth, blood
      samples were obtained from infants. Demographic and baseline characteristics were
      compared between groups. Birth weight, length and head circumference of neonates
      in the FGR group were lower than those in the control group. Total serum IgE
      level was significantly increased in third-trimester pregnant women with FGR
      compared with normal group (P < 0.05). However, this trend was not observed in
      the cord blood at birth or peripheral blood of 6-month-old infants. The
      prevalence of atopic eczema between the 2 groups was similar. Linear regression
      analysis revealed that the IgE level in the third trimester was negatively
      correlated with birth weight (P < 0.05). Higher serum IgE level in the cord blood
      was significantly associated with an increased risk of being small for
      gestational age (P < 0.05). In conclusion, IgE levels in the third trimester of
      pregnancy and cord blood are strongly related to birth outcomes of FGR. 

PMID- 25966160
TI  - Immunohistochemical subtypes of diffuse large B-cell lymphoma in the head and
      neck region.
AB  - The objectives of this study were to detect immunohistochemical subtypes of
      diffuse large B-cell lymphoma (DLBCL) of the head and neck, to compare the Hans,
      Choi, and Tally algorithms and to examine the significance of protein expression
      in these algorithms. This study included 103 DLBCL patients at Sichuan Cancer
      Hospital between May 2010 and October 2012. Immunohistochemistry was per-formed
      for CD10, B-cell lymphoma 6 protein (Bcl-6), mutated melanoma-associated antigen
      1 (MUM1), germinal center B-cell-expressed transcript 1 (GCET1), forkhead box
      protein P1 (FOXP1), and LIM do-main only 2 (LMO2). Subtypes were determined
      according to the Hans, Choi, and Tally algorithms. Positive staining for CD10 was
      detected in 16 patients (15.53%), for Bcl-6 in 68 patients (66.02%), for MUM1 in
      69 patients (66.99%), for GCET1 in 21 patients (20.39%), for FOXP1 in 75 patients
      (72.82%), and for LMO2 in 50 patients (48.54%). The Hans algorithm identified 26
      patients (25.2%) with the germinal center B-cell (GCB) subtype and 77 (74.8%)
      with the activated B-cell (ABC) subtype. In the Choi algorithm, 25 patients
      (24.3%) were identified with the GCB subtype and 78 (75.7%) with the ABC subtype.
      In the Tally algorithm, 20 patients (19.4%) had the GCB subtype and 83 (80.6%)
      had the ABC subtype. Expression of CD10, MUM1, GCET1, FOXP1, and LMO2 correlated
      with algorithm (P < 0.05); however, Bcl-6 did not correlate with the Hans and
      Choi algorithms. DLBCL of the head and neck is most commonly the ABC subtype, not
      GCB. The Hans, Choi, and Tally algorithms were not significantly different.

PMID- 25966161
TI  - Effects of p-chlorophenoxyisobutyric acid, arabinogalactan, and activated
      charcoal on microspore embryogenesis in kale.
AB  - To improve embryogenesis in microspore cultures of kale (Brassica oleracea L.
      var. acephala DC.), 6-benzylaminopurine (6-BA), naphthaleneacetic acid (NAA),
      arabinogalactan (AG), p-chlorophenoxyisobutyric acid (PCIB), and activated
      charcoal (AC) were added to the medium using four varieties of kale. The results
      showed that the addition of AG (0.1-0.2 g/L), AC (0.1-0.2 g/L) or a combination
      of 6-BA (0.1-0.2 mg/L) and NAA (0.1-0.2 mg/L) promoted embryo-genesis. Adding 40
      MUM PCIB or a combination of 40 MUM PCIB and 0.2 g/L AC to NLN-13 medium at pH
      5.8 effectively enhanced embryogenesis. Treatment with a combination of 40 MUM
      PCIB and 10 mg/L AG gave the highest rate of embryonic induction, especially in
      genotype "Y007," which showed a twelve-fold increase in yield.

PMID- 25966162
TI  - Selected representative microsatellite loci for genetic monitoring and population
      structure analysis of miniature swine.
AB  - To optimize the combination of microsatellite loci for genetic control of outbred
      swine stocks, 32 of 100 loci distributed among almost all chromosomes (except 12)
      were screened out by 1.5% agarose, 8% polyacrylamide gel and capillary
      electrophoresis scanning among 3 miniature swine outbred stocks, namely Bama
      (BM), Guizhou (GZ) and Tibeta (TB). The mean total and effective allele numbers
      among these stocks were 12.1 and 5.9, respectively. The mean heterozygosity for
      these breeds was 0.5428, 0.6978 and 0.7646, and polymorphism information content
      was 0.5469, 0.7296 and 0.7663, respectively. Accordingly, hereditary variation
      from low to high was BM < GZ < TB. This showed that the genetic relationship
      between BM and GZ pigs was closer, and both were distant from TB. Additionally,
      the effectiveness of the 32-locus combination for evaluation of genetic quality
      was demonstrated in Changchun-junmo-1 (CJ-1), a standard outbred Chinese pig
      stock, in which the mean total and effective allele numbers and mean
      heterozygosity were 6.1613, 3.8483 and 0.6903, respectively. Since our results
      were consistent with the breeding pedigrees, the 32 loci could be used for both
      genetic monitoring within the individual outbred miniature swine stocks and
      population structure analysis between them. 

PMID- 25966163
TI  - CYFRA21-1 levels could be a biomarker for bladder cancer: a meta-analysis.
AB  - The proteolytic region of cytokeratin-19, referred to as CYFRA21-1, is a soluble
      molecule present in the serum and other body fluids, and is considered a tumor
      marker in several neoplastic diseases. To examine whether urinary or serum
      samples containing CYFRA21-1 can be used as biomarkers for bladder cancer, we
      conducted a comprehensive meta-analysis of 3 case-control studies. In all studies
      considered, patients with bladder cancer had a higher CYFRA21-1 level than
      healthy subjects. Subgroup analysis showed that patients with metastatic bladder
      cancer had a higher CYFRA21-1 level than those with locally invasive disease.
      However, no significant difference in CYFRA21-1 was observed between patients
      with stage I and stage II bladder cancer; there was also no difference in
      patients with stage II local bladder cancer and those with stage III local
      bladder cancer. Based on our results, CYFRA21-1 level may be a diagnostic
      biomarker for diagnosing bladder cancer as well as a possible biomarker for
      differentiation between local and metastatic bladder cancer. However, it cannot
      be used as a urinary or serum biomarker for differentiating histological stages
      of local bladder cancer for histological grades I-III. 

PMID- 25966164
TI  - Co-culture of annulus fibrosus cells and bone marrow mesenchymal stem cells.
AB  - To investigate the effect on cell proliferation and extracellular matrix
      expression of annulus fibrosus (AF) cells when co-cultured with bone marrow
      mesenchymal stem cells (BMSCs). Primary isolated rabbit BMSCs and AF cells were
      cultured and harvested cells were placed into a 15-mL centrifugal tube co-culture
      system in a ratio of 2:1 (A group), 1:1 (B group), and 1:2 (C group). Cell
      proliferation was evaluated using cell counting kit-8, and mRNA of collagen II
      and mucopolysaccharide was quantified using real-time polymerase chain reaction
      (PCR) on Days 7, 14, and 21. The cell count, synthesized collagen II and
      mucopolysaccharide increased in a time-dependent manner, with a peak at Day 21.
      Cells in Group B proliferated faster and synthesized more collagen II and
      mucopolysaccharide than groups A and C, where the difference was significant. AF
      cells and BMSCs in the ratio of 1:1, cultured using the centrifugal tube three
      dimensional co-culture system showed that BMSCs can promote AF cell proliferation
      and extracellular matrix synthesis.

PMID- 25966165
TI  - High-resolution color doppler ultrasound examination and related risk factor
      analysis of lower extremity vasculopathy in type 2 diabetes patients.
AB  - This study aims to investigate the value of high-resolution color Doppler
      ultrasonography (HR-CDU) in the evaluation of lower-extremity vasculopathy (LEV)
      and its related risk factors in type 2 diabetes mellitus (T2DM) patients. Two
      hundred forty T2DM patients were selected, who underwent lower-extremity arterial
      HR-CDU. The patients were divided into the LEV group (V group) and the
      nonvasculopathy group (A group). The V group was then divided into the mild (B
      group), moderate (C group), and severe (D group) subgroups. The relevant clinical
      parameters were simultaneously recorded. The results showed that the lesion
      positive detection rate of HR-CDU was significantly higher than that of clinical
      examination. The age, disease duration, smoking history, blood pressure, blood
      sugar, fibrinogen (FIB), C-reactive protein (CRP), uric acid (UA), and urinary
      albumin excretion (UAE) in the V group were higher than in the N group. In the
      logistic regression analysis, smoking history, age, disease duration, FIB, UA,
      and fasting blood glucose were independent risk factors of T2DM LEV. The
      incidence of LEV in T2DM patients increased significantly with increasing age,
      UA, FIB, CRP, UAE, disease duration, and smoking history, and the vasculopathy
      level became more severe. In conclusion, age, disease duration, smoking history,
      blood pressure, blood sugar, FIB, CRP, UA, and UAE are the related risk factors
      of LEV in T2DM patients. 

PMID- 25966166
TI  - Expression profiles of retinoic acid synthetases ALDH1As and metabolic enzymes
      CYP26s in adult and embryonic zebrafish (Danio rerio).
AB  - Retinoic acid (RA) plays a crucial role in cellular proliferation,
      differentiation, and apoptosis. The physiological activity of RA begins early in
      development and continues throughout an organism's life. RA distribution is
      tightly controlled by the RA synthetases ALDH1As and the metabolic enzymes
      CYP26s. We analyzed the expressions of ALDH1As and CYP26s in whole embryos during
      zebrafish (Danio rerio) development and in adult zebrafish organs, by
      quantitative reverse transcriptase polymerase chain reaction analysis. All the
      ALDH1A and CYP26 genes exhibited similar pulse expression patterns, with peak
      expressions at different developmental stages. ALDH1A2 exhibited an earlier and
      sharper expression peak [12 hours post-fertilization (hpf)] than ALDH1A3 (24
      hpf). CYP26A1 transcription peaked earlier (8 hpf) than CYP26B1 and CYP26C1 (12
      hpf), while CYP26C1 expression dropped to basal levels later (48 hpf) than that
      of CYP26A1 and CYP26B1 (18 hpf). ALDH1A2 and CYP26A1 exhibited the highest mRNA
      peak level and seem to be the dominant isoenzymes in their families during
      zebrafish development. Expression patterns of ALDH1As and CYP26s in most adult
      zebrafish tissues were similar to those in humans. Nevertheless, three CYP26s
      were more vigorously expressed in the zebrafish brain than in human organs,
      whereas much weaker ALDH1A and CYP26 transcription was found in the zebrafish
      liver and intestine. This suggests that RA metabolic rates differ between
      zebrafish and humans or that other enzymes are responsible for RA homeostasis in
      the zebrafish liver and intestine. All the ALDH1A and CYP26 genes exhibited
      distinct expression patterns during zebrafish development and in adult zebrafish
      tissues. 

PMID- 25966167
TI  - Rapid discrimination between four seagrass species using hybrid analysis.
AB  - Biological species are traditionally identified based on their morphological
      features and the correct identification of species is critical in biological
      studies. However, some plant types, such as seagrass, are taxonomically
      problematic and difficult to identify. Furthermore, closely related seagrass
      species, such as Halophila spp, form a taxonomically unresolved complex. Although
      some seagrass taxa are easy to recognize, most species are difficult to identify
      without skilled taxonomic or molecular techniques. Barcoding coupled with High
      Resolution Melting analysis (BAR-HRM) offers a potentially reliable, rapid, and
      cost-effective method to confirm species. Here, DNA information of two
      chloroplast loci was used in combination with HRM analysis to discriminate four
      species of seagrass collected off the southern coast of Thailand. A distinct
      melting curve presenting one inflection point was generated for each species
      using rbcL primers. While the melting profiles of Cymodocea rotundata and
      Cymodocea serrulata were not statistically different, analysis of the normalized
      HRM curves produced with the rpoC primers allowed for their discrimination. The
      Bar-HRM technique showed promise in discriminating seagrass species and with
      further adaptations and improvements, could make for an effective and power tool
      for confirming seagrass species. 

PMID- 25966168
TI  - Cytoplasmic polymorphism and evolutionary history of plum cultivars: Insights
      from chloroplast DNA sequence variation of trnL-trnF spacer and aggregated trnL
      intron & trnL-trnF spacer.
AB  - We screened for polymorphisms of the non-coding region of plastid DNA in plum
      trees. Sequencing data from the trnL-trnF chloroplast region were used to reveal
      a pattern of diversity, establish phylogenetic relationships, and test the
      selection pressure or evolutionary demography scenario for plastome DNA. The size
      of the non-coding regions varied from 398 to 563 and 865 to 1084 bases pairs for
      the trnL-trnF spacer and combined sequences, respectively. The average GC
      contents were 33.8 and 34.4% in the spacer and pooled sequences, respectively.
      Genetic distances calculated within the plums were 0.077 and 0.254, on average,
      for the trnL spacer and combined sequences, respectively. The neighbor-joining
      trees showed clustering relationships among cultivars that were independent of
      their geographic origins and designations. The neutrality tests and site
      frequency spectra indicated that spacer and pooled sequences fit the neutral
      theory model at equilibrium between mutation and genetic drift and reject the
      hypothesis of a recent demographic expansion. The mismatch distribution shows
      variation patterns, thus providing evidence of an important genetic diversity
      explained by an excess of intermediate variants that occurred in the sequences
      analyzed. Further implications of the findings with regard to plum germplasm
      management and its utilization in breeding programs are also discussed. 

PMID- 25966169
TI  - Development of novel microsatellite markers for conservation genetic studies of
      Vulpes vulpes (Canidae) by using next-generation sequencing method.
AB  - The red fox, Vulpes vulpes (Canidae), is the most widely distributed terrestrial
      carnivore worldwide, but this species is classified as endangered in Korea. In
      this study, we developed 25 polymorphic microsatellite markers that included 3-13
      (mean = 6.32) alleles per locus using 22 red fox individuals. The most
      polymorphic locus was FR(59)TG (13 alleles) and the least polymorphic loci were
      FR(70)TG and FR(182)AG (3 alleles each). No significant deviation from Hardy
      Weinberg equilibrium (P < 0.05) was observed for the 25 markers. Observed (HO)
      and expected (HE) heterozygosity varied from 0.182 to 1.000 and from 0.175 to
      0.929, respectively. These newly developed microsatellite markers will be useful
      for investigating the genetic diversity and population genetic structure of V.
      vulpes and will aid in developing conservation strategies for this species. 

PMID- 25966170
TI  - Effect of Fimbristylis ovata on receptor for advanced glycation end-products,
      proinflammatory cytokines, and cell adhesion molecule level and gene expression
      in U937 and bEnd.3 cell lines.
AB  - Fimbristylis ovata has been long used as a traditional medicine for chronic
      inflammatory diseases; however, there are no data regarding its anti-inflammatory
      properties. In this study, we investigated the effects of F. ovata extracts on
      the secretion of pro-inflammatory cytokines, cell adhesion molecule, and receptor
      for advanced glycation end-products (RAGE) in lipopolysaccharide-stimulated
      cells. F. ovata was extracted using the maceration method with 3 different
      solvents: ethanol, methanol, and water. The effect of F. ovata extracts on cell
      viability was evaluated using the MTT assay. Pro-inflammatory cytokines and cell
      adhesion molecules were investigated by reverse transcription-polymerase chain
      reaction and an enzyme-linked immunosorbent assay. Upon incubation with F. ovata
      extracts up to 100 mg/mL, cell viability was more than 80%. F. ovata extracts
      could inhibit interleukin-6 level and gene expression as well as the RAGE gene in
      the monocytic cell lineU937. Moreover, the results showed that vascular cell
      adhesion molecule 1 secretion and gene expression were decreased when
      lipopolysaccharide-activated brain endothelial cells (bEnd.3) were treated with
      F. ovata extracts. Therefore, the anti-inflammatory activity of F. ovata extracts
      may result from their inhibitory actions via the RAGE signaling pathway. 

PMID- 25966171
TI  - Identification of differentially expressed genes in a pistillody common wheat
      mutant using an annealing control primer system.
AB  - HTS-1 is a new kind of pistillody wheat. All or parts of its stamen are
      transformed into pistils or pistil-like structures, and it has more seed sets per
      floret than normal wheat under normal cultivation conditions. To investigate the
      expression divergence in this mutant, an annealing control primer system was used
      to identify differentially expressed genes (DEGs) in the young spikelets. As a
      result, three DEGs, including HDB2, HGF2, and HCG4, were detected, with variable
      expression in HTS-1 and the control. After further confirmation using real-time
      reverse transcription polymerase chain reaction analysis, these genes were
      overexpressed in HTS-1 wheat. NGF2 was identified in the double ridge to floret
      differentiation stages; HDB2 and HCG4 were identified in the stage of pistil and
      stamen-differentiating. Therefore, we inferred that the homeotic transformation
      of stamens into pistil-like structures occurred during the early stage of stamen
      development. Sequence alignment analysis revealed that HDB2 encodes a putative
      protein of 189 amino acids, with high homology to the DEAD-box ATP-dependent RNA
      helicase, and HCG4 was identical to the Chinese spring wheat cDNA clone predicted
      protein according to GenBank. However, NGF2 was not found to have significant
      similarity to any reported proteins, suggesting it is a new functional gene in
      wheat. The results suggest that HDB2, HCG4, and HGF2 are minor genes contributing
      to pistillody trait formation in HTS-1. 

PMID- 25966172
TI  - Role of the CKIP1 gene in proliferation and apoptosis of the human lung cancer
      cell line H1299.
AB  - Casein kinase 2 interacting protein 1 (CKIP1) is a specific interacting protein
      of the casein kinase 2 (CK2) alpha subunit, and, by binding CK2 and other
      proteins, functions as an adaptor to regulate a series of cellular functions.
      Previous studies suggested that CKIP1 might play an important role in regulating
      oncogenic activities. However, few studies examining the function of CKIP1 in
      cancer cells have been performed. The present study aimed to investigate the role
      of CKIP1 in lung cancer. CKIP1 mRNA expression was detected in 5 human lung
      cancer cell lines (H-125, H1299, LTEP-A-2, SPC-A-1, and NCL-H446) by semi
      quantitative RT-PCR, and in 10 noncancerous lung tissues and 30 non-small lung
      cancer tissues by real-time quantitative PCR. A lentivirus-mediated small
      interfering RNA (siRNA) was used to knock down CKIP1 expression in the H1299 cell
      line. To elucidate the impact of CKIP1 downregulation on H1299 cells, cell
      proliferation, DNA synthesis, and cell cycle distribution and apoptosis were
      measured by high content screening assay, BrdU incorporation, and flow cytometric
      analyses, respectively. CKIP1 mRNA was highly expressed both in H1299 cells and
      lung cancer tissues. We found that downregulation of CKIP1 resulted in
      suppression of proliferation and colony-forming ability of H1299 cells, and led
      to S phase cell cycle arrest and G2 phase promotion, as well as a significant
      enhancement of H1299 cell apoptosis. Our study indicated that high expression
      levels of CKIP1 were associated with the development of lung cancer, and that
      CKIP1 knockdown may block tumor cell growth mainly by promoting cell apoptosis. 

PMID- 25966173
TI  - Association of the C677T polymorphism in the methylenetetrahydrofolate reductase
      gene with breast cancer in a Mexican population.
AB  - The methylenetetrahydrofolate reductase (MTHFR) gene plays an important role in
      the steps involved in the processing of amino acids. The analysis of
      polymorphisms in the MTHFR gene has revealed associations with cancer; in
      particular the C677T polymorphism, which has been suggested to affect folate
      metabolism, DNA methylation, synthesis, and repair, and to contribute to tumor
      promotion in the mammary gland. We examined the role of the C677T polymorphism in
      the MTHFR gene by comparing the C677T genotypes of 339 healthy Mexican women with
      those of 497 Mexican women with breast cancer (BC). The genotype frequencies
      observed in the controls and patients with BC were 10 and 21% for 677TT; 41 and
      36% for 677CT; and 49 and 43% for 677CC, respectively. The odds ratio (OR) for
      the 677TT genotype was 2.5, with a 95% confidence interval (95%CI) of 1.6-3.8; P
      = 0.0001. The positive association was also evident when the distributions of the
      677TT genotype in control and patients affected within the following two
      categories were compared to alcohol consumption (OR = 0.41; 95%CI = 0.19-0.86; P
      = 0.018); and high level glutamate-oxaloacetate transaminase (SGOT) (OR = 0.36;
      95%CI = 0.15-0.83, P = 0.017). These results suggest that the 677TT genotype of
      the C677T polymorphism in the MTHFR gene is associated with BC susceptibility in
      the Mexican population. 

PMID- 25966174
TI  - Analysis and clinical significance of microRNA-499 expression levels in serum of
      patients with acute myocardial infarction.
AB  - The aim of this study was to investigate the expression level of microRNA-499 and
      its clinical significance in serum of patients with acute myocardial infarction
      (AMI). We recruited 59 patients with AMI and 60 healthy individuals undergoing
      physical examination in our hospital during the same period as controls.
      Peripheral blood was drawn in the morning on the same day of microRNA extraction.
      The expression level of microRNA-499 was analyzed by real-time fluorescent
      quantitative polymerase chain reaction (qPCR). The sensitivity and specificity of
      the clinical diagnosis of AMI were analyzed by a receiver operating
      characteristic (ROC) curve. Fluorescent qPCR analysis showed that the expression
      of microRNA-499 in serum of patients with AMI was significantly higher than in
      controls (P < 0.05). MicroRNA-499 was detected in blood serum 3 h post-AMI,
      reaching a peak after 12 h and declining after 15 h. The area under the ROC curve
      (AUC) for the gold standard cardiac troponin I (cTnI) was 0.971 [95% confidence
      interval (CI): 0.951-1.000], and for the microRNA-499, AUC = 0.915 (95%CI: 0.826
      1.000). When the microRNA-499 levels in patient and control (> 1.5) sera were
      compared, the sensitivity of microRNA-499 in judging AMI was found to be 86.37%
      and the specificity was 93.47%. Our results demonstrated that the expression
      levels of microRNA-499 in serum of patients with AMI were abnormal. Its high
      sensitivity and specificity for the diagnosis of AMI suggest that it would be
      useful as an auxiliary index for clinical diagnosis of AMI. 

PMID- 25966175
TI  - MCP-1 gene polymorphisms in North Chinese patients with pulmonary tuberculosis.
AB  - Pulmonary tuberculosis (PTB) remains one of the most important infectious
      diseases worldwide. Several studies have suggested that genetic factors may
      affect the susceptibility to PTB, but the specific genes involved have not been
      fully characterized. The gene for monocyte chemoattractant protein 1 (MCP-1) has
      been linked to an increased risk of tuberculosis in some Mexican and Korean
      populations. To explore the role of the MCP-1 gene in the susceptibility to PTB
      in a North Chinese population, we evaluated the association between MCP-1 
      2518A/G gene polymorphisms and the risk for tuberculosis. Polymerase chain
      reaction amplification of genomic DNA followed by restriction fragment length
      polymorphism analysis was used. There was a significant increase in the frequency
      of the GG genotype of MCP-1 -2518 in 136 patients with PTB compared to that in
      152 healthy controls (P = 0.008, X(2) = 7.133, odds ratio = 1.96). Similarly, the
      frequencies of the A/G alleles in the 2 groups differed; the frequency of allele
      G was higher in patients with PTB (P = 0.011, X(2) = 6.428, odds ratio = 1.536).
      In conclusion, the -2518A/G polymorphism in the MCP-1 gene was found to be
      associated with an increased susceptibility to PTB in a North Chinese population.

PMID- 25966176
TI  - Single-nucleotide polymorphisms in dopamine receptor D1 are associated with
      heroin dependence but not impulsive behavior.
AB  - Previous studies suggested that dopamine receptors may be associated with drug
      dependence and impulsive behavior. In this study, we examined whether dopamine
      receptor D1 (DRD1) is associated with heroin dependence and the impulsive
      behavior in patients with heroin dependence. The participants included 367
      patients with heroin dependence and 372 healthy controls from a Chinese Han
      population. We examined the potential association between heroin dependence and 8
      single-nucleotide polymorphisms (rs686, rs4867798, rs1799914, rs4532, rs5326,
      rs265981, rs10078714, rs10078866) of DRD1, and the associations between single
      single-nucleotide polymorphism, haplotypes, and impulsive behavior. Compared with
      the healthy controls, heroin dependence patients showed a significantly lower
      frequency of GG homozygotes of rs5326 (P = 0.027), significantly lower frequency
      of the G allele of rs5326 (P = 0.007, odds ratio = 0.718, 95% confidence interval
      = 0.565-0.913), and higher frequency of the rs265981 G allele (P = 0.0002, odds
      ratio = 1.711, 95% confidence interval = 1.281-2.287). Furthermore, strong
      linkage disequilibrium was observed in 2 blocks (D' > 0.9). However, no
      association was observed between haplotypes and heroin dependence in the 2
      blocks. This genetic behavior correlation study showed that the 2 single
      nucleotide polymorphisms, rs5326 and rs265981, were not associated with the
      impulsive behavior in patients with heroin dependence. These findings indicate
      that DRD1 gene polymorphisms are related to heroin dependence in a Chinese Han
      population and may be informative for future genetic or biological studies on
      heroin dependence. 

PMID- 25966177
TI  - Cytogenetic description of Ancistrus abilhoai (Siluriformes: Loricariidae) from
      Iguacu River basin, southern Brazil.
AB  - The Iguacu River basin is a tributary to the upper Parana River in southern
      Brazil, and is considered an important aquatic ecoregion that, although having
      few species of fish, 51-71% of these are apparently endemic. Ancistrus abilhoai
      is one of three recently described species for this basin and is currently
      considered endemic to the basin. In this study, we present the chromosomal
      structure of two populations of Ancistrus abilhoai one collected in the Iguacu
      River, in Parana State, and another collected in the Timbo River, a tributary of
      the Iguacu River, in the State of Santa Catarina. Karyotype analyzes were
      performed in 11 specimens from the Iguacu River (four females and seven males)
      and 12 specimens (all males) from Timbo River, revealing 2n = 48 chromosomes with
      a karyotype formula of 22m + 14sm + 6st + 6a in both populations. Analysis of
      active nucleolar organizer regions (Ag-NORs) and fluorescent in situ
      hybridization (FISH) with 18S rDNA probes revealed the submetacentric pair 13
      bearing marks at terminal positions on the short arms. Considered as
      plesiomorphic chromosomal markers in Loricariidae, asynteny 18S and 5S rDNA, and
      small amounts of heterochromatin were observed. In this study, the first
      chromosomal data of A. abilhoai are presented with comments on karyotypic
      characteristics of the genus.

PMID- 25966178
TI  - Overexpression of pucC improves the heterologous protein expression level in a
      Rhodobacter sphaeroides expression system.
AB  - The Rhodobacter sphaeroides system has been used to express membrane proteins.
      However, its low yield has substantially limited its application. In order to
      promote the protein expression capability of this system, the pucC gene, which
      plays a crucial role in assembling the R. sphaeroides light-harvesting 2 complex
      (LH2), was overexpressed. To build a pucC overexpression strain, a pucC
      overexpression vector was constructed and transformed into R. sphaeroides CQU68.
      The overexpression efficiency was evaluated by quantitative real-time polymerase
      chain reaction. A well-used reporter beta-glucuronidase (GUS) was fusion
      expressed with LH2 to evaluate the heterologous protein expression level. As a
      result, the cell culture and protein in the pucC overexpression strain showed
      much higher typical spectral absorption peaks at 800 and 850 nm compared with the
      non-overexpression strain, suggesting a higher expression level of LH2-GUS fusion
      protein in the pucC overexpression strain. This result was further confirmed by
      Western blot, which also showed a much higher level of heterologous protein
      expression in the pucC overexpression strain. We further compared GUS activity in
      pucC overexpression and non-overexpression strains, the results of which showed
      that GUS activity in the pucC overexpression strain was approximately ten-fold
      that in the non-overexpression strain. These results demonstrate that
      overexpressed pucC can promote heterologous protein expression levels in R.
      sphaeroides. 

PMID- 25966179
TI  - A new repertoire of informations about the quorum sensing system in Salmonella
      enterica serovar Enteritidis PT4.
AB  - Salmonella spp are among the main causative agents of foodborne diseases. Some
      phenotypes associated with increased drug resistance and virulence are regulated
      by quorum sensing (QS). In the present study, the autoinducer (AI)-1- and -2
      mediated QS mechanisms were characterized in Salmonella enterica serovar
      Enteritidis PT4 for the first time. Salmonella Enteritidis did not produce AI-1.
      Phylogenetic analysis of nucleotides encoding the SdiA protein, the response
      regulator of AI-1-mediated QS, and comparative alignment of its amino acids
      showed that the gene and protein are conserved within the same bacterial genus.
      Thus, bacteria of the same genus respond to the same AIs. However, this finding
      did not preclude the possibility that Salmonella Enteritidis might respond to AIs
      released from bacteria of a different genus, which might confer a competitive
      advantage to this pathogen. We found that the regulation of AI-2-mediated QS in
      Salmonella Enteritidis is similar to that in serovar Typhimurium. The elucidation
      of the AI-1- and AI-2-mediated QS mechanisms in Salmonella Enteritidis will
      contribute to the development of new control strategies for this pathogen by
      indicating new targets for antimicrobial drugs. 

PMID- 25966180
TI  - 3'-UTR polymorphism (rs10434) in the VEGF gene is associated with B-CLL in a
      Chinese population.
AB  - We investigated the relationship between a VEGF genetic polymorphism and B cell
      chronic lymphocytic leukemia (B-CLL). A total of 102 patients with B-CLL and 124
      healthy subjects were included in this study. All individuals were typed for the
      rs10434 in the vascular endothelial growth factor (VEGF) gene using the TaqMan
      technique. We found that the A allele and the AA genotype of rs10434 were more
      frequent in B-CLL patients than in control subjects (0.54 vs 0.34; 27 vs 13%;
      respectively). VEGF alleles and genotypes segregated similarly in patients at
      different disease stages according to Rai classification. These results suggest a
      possible association between the VEGF polymorphism and high-risk B-CLL. 

PMID- 25966181
TI  - Single nucleotide polymorphism analysis of the endopolygalacturonase gene in
      peach and its potential use in crossbreeding programs.
AB  - Single nucleotide polymorphisms (SNPs) are the most abundant sequence variations
      found in plant genomes and are widely used as molecular genetic markers in
      genetic diversity studies and crossbreeding programs. In this study, we examined
      113 DNA sequences of the endopolygalacturonase (endo-PG) gene from 67 peach
      accessions and found a total of 56 SNPs and 6 insertion/deletions (indels), with
      a frequency of 3, 1, and 3% for the transitions, transversions, and indels,
      respectively. Meanwhile, the majority of the observed SNPs were found in the
      intron regions, while only 2 variable sites and a single indel were detected in
      the exon regions. A dendrogram was obtained using neighbor-joining cluster
      analysis and divided into 2 main groups, providing evidence that most of the
      accessions of the clingstone nonmelting flesh phenotypes generally clustered
      together and were comparatively nonrelated to the "stony hard" peach cultivars,
      which were in a different branch altogether. Furthermore, 4 major haplotypes were
      formed and 3 cleaved amplified polymorphic sequence primer sets were mined
      according to fruit texture and stone adhesion, displaying their potential as
      candidate molecular markers for discriminating genotypes. This research will
      assist peach genetic enhancement by introducing a novel crossbreeding strategy. 

PMID- 25966182
TI  - Effects of autologous SCF- and G-CSF-mobilized bone marrow stem cells on hypoxia
      inducible factor-1 in rats with ischemia-reperfusion renal injury.
AB  - To explore the mechanism whereby stem cell factor (SCF) and granulocyte colony
      stimulating factor (G-CSF) jointly mobilize bone marrow stem cells (BMSCs) and
      promote kidney repair, male Sprague-Dawley rats were randomly assigned into 4
      groups. In the treatment control group, rats were administered SCF (200 MUg.kg(
      1).day(-1)) and G-CSF (50 MUg.kg-1.day-1) for 5 days. In the treatment group,
      RIRI models were established, and 6 h later, SCF (200 MUg.kg(-1).day(-1)) and G
      CSF (50 MUg.kg(-1).day(-1)) were administered for 5 days. In the model and
      treatment groups, tubular epithelial cell degeneration and necrosis were noticed,
      but the extent of repair in the treatment group was significantly better than in
      the model group. Five days after the operation, renal tissue CD34+ cells
      significantly increased in the model and treatment groups compared with the
      control and treatment control groups. HIF-1alpha, VEGF, and EPO expression in
      treatment groups increased significantly compared with the other groups. HIF-
      1alpha, VEGF, EPO expression in the treatment control group increased
      significantly compared with the control group. Joint use of SCF and G-CSF
      increased the number of BMSCs in damaged kidney tissue and reduced the degree of
      renal tissue damage. BMSCs promote increased HIF-1alpha expression in renal
      tissue. Increased kidney tissue HIF- 1alpha and its target gene products VEGF and
      EPO expression possibly induce SCF and G-CSF to promote acute tubular necrosis
      repair.

PMID- 25966183
TI  - Mating system patterns of natural populations of Pinus koraiensis along its post
      glacial colonization route in northeastern China.
AB  - To understand the genetic mechanisms underlying the endangerment of Pinus
      koraiensis, we studied the mating system of 49 families of this species in 3
      natural populations along its post-glacial colonization route across ~1500 km in
      northeastern China using the chloroplast simple sequence repeat technique. We
      analyzed 11 polymorphic loci with clear and repeating bands, and we calculated
      the multi-locus outcrossing rate (tm), single-locus outcrossing rate, inbreeding
      index, and fixation index (F). Intra-population variation was not observed, but a
      large inter-population variation was observed in the outcrossing rate, and the tm
      increased from 0.767 (the south population) to 0.962 (the north population) along
      the post-glacial colonization route. The tm values within a population did not
      change with time over 2 consecutive years. The F values for the 3 populations
      were <0, which indicates an excess of heterozygotes. The mean effective number of
      alleles, Shannon diversity index, and Nei's genetic diversity index did not show
      a south-north pattern. The north population had the highest outcrossing rate but
      the lowest genetic diversity. The average genetic differentiation of P.
      koraiensis populations was 0.1251, which was within the average range of woody
      plants with outcrossing and wind pollination. This study suggests that the
      current endangerment of P. koraiensis is not related to its genetic structure;
      perhaps it is mainly caused by man-made and natural disturbances such as
      deforestation and fire. Therefore, reducing disturbances and enhancing habitats,
      rather than the genetic aspects, play more important roles in the long-term
      protection of P. koraiensis. 

PMID- 25966184
TI  - A novel FBN1 heterozygous mutation identified in a Chinese family with autosomal
      dominant Marfan syndrome.
AB  - The purpose of this study was to identify the clinical features and mutations in
      the fibrillin-1 gene (FBN1) in a large Chinese family with autosomal dominant
      Marfan syndrome (MFS). Seventeen members from a Chinese family of 4 generations
      were included in the study. All members underwent complete ophthalmic
      examination. Molecular genetic analysis was performed on all subjects. All exons
      of FBN1 were amplified by polymerase chain reaction, sequenced, and the sequences
      were compared with a reference database. Variations were evaluated in family
      members as well as 100 normal controls. Changes in structure and function of the
      protein induced by amino acid variation were predicted by bioinformatic analysis.
      Ectopia lentis, dolichostenomelia, arachnodactyly, and tall stature were present
      in all patients diagnosed with MFS. The novel heterozygous missense mutation
      c.2243 T>G (p.C781W) in exon 19 of FBN1 was identified in all 5 patients, but not
      in other family members or 100 normal controls. This mutation caused an amino
      acid substitution of cysteine to tryptophan at position 781 (p.C781W) of the FBN1
      protein. This mutation occurred in a highly conserved region and may cause
      structural and functional changes in the protein according to our bioinformatic
      analysis. Our results suggest that the novel mutation C781W of FBN1 is
      responsible for the pathogenesis of MFS in this pedigree. 

PMID- 25966185
TI  - Meta-analysis of microsomal epoxide hydrolase gene polymorphism and the risk of
      breast carcinoma.
AB  - Carcinogenesis of breast carcinoma is very complicated. Previous studies have
      suggested conflicting results regarding the association between Tyr113His and
      His139Arg microsomal epoxide hydrolase (mEH) gene polymorphisms and risk of
      breast carcinoma. We conducted a meta-analysis to examine the relationship
      between these polymorphisms and breast carcinoma risk. We searched the PubMed,
      EMBASE, and Google Scholar databases to identify relevant studies. After
      extracting relevant data, the association between mEH polymorphisms and
      susceptibility to breast carcinoma was examined by meta-analysis. Odds ratios
      (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength
      of the association. Seven studies were identified that included 6357 cases and
      8090 controls. The mEH His-allele was not associated with the risk of breast
      carcinoma based on the allelic contrast model (OR = 0.99, 95%CI = 0.94-1.04, P =
      0.58), dominant genetic model (OR = 1.14, 95%CI = 0.88-1.48, P = 0.33), or
      recessive genetic model (OR = 1.03, 95%CI = 0.96-1.10, P = 0.43). Similarly, the
      mEH Arg-allele was not associated with breast carcinoma risk based on the allelic
      contrast model (OR = 0.97, 95%CI = 0.91-1.04, P = 0.44), dominant genetic model
      (OR = 1.01, 95%CI = 0.84-1.21, P = 0.94), or recessive genetic model (OR = 1.04,
      95%CI = 0.96-1.12, P = 0.35). Subgroup analysis based on ethnicity showed no
      association between the polymorphisms and risk of breast carcinoma. Thus, the
      Tyr113His and His139Arg mEH polymorphisms may not be risk factors for breast
      carcinoma. 

PMID- 25966186
TI  - Association between polymorphisms in the adiponectin gene (APM-1) and
      atherosclerotic cerebral infarction in a Hainan Chinese Han population.
AB  - We investigated the association between polymorphisms in the adiponectin gene
      (APM-1) and atherosclerotic cerebral infarction (ACI) in a Chinese Han population
      of Hainan Province. Polymerase chain reaction-restriction fragment length
      polymorphism and gene sequencing were used to analyze the distribution of APM-1
      +45T/G and +276G/T genotypes and their alleles in 120 ACI patients and 120
      healthy controls. No statistical correlation was found in the frequency and
      distribution of the genotype 45T/G between the ACI group and the control group.
      Genotypic frequencies of GG, GT, and TT at the APM-1 +276 locus were 70.0%
      (84/120), 25.0% (30/120), and 5.0% (6/120), respectively, in the ACI group, while
      these values were 52.5% (63/120), 37.5% (45/120), and 10.0% (12/120),
      respectively, in the control group. The frequency of the G allele was 82.5%
      (198/240) in the ACI group and 71.25% (171/240) in the control group. The T
      allele frequency was 17.5% (42/240) in the ACI group and 28.75% (69/240) in the
      control group. Polymorphisms at the APM-1 -276 locus in the case-controlled
      groups showed significant differences in the genotype distribution and al-lele
      frequency between the 2 groups (P = 0.041). The occurrence of ACI in the Hainan
      Chinese Han population may be associated with +276G/T polymorphisms but not with
      +45T/G polymorphisms in the APM-1 gene. 

PMID- 25966187
TI  - MicroRNA-21 promotes proliferation of rat hepatocyte BRL-3A by targeting FASLG.
AB  - Rat liver regeneration (RLR) induced by partial hepatectomy involves cell
      proliferation regulated by numerous factors, including microRNAs (miRNAs). miRNA
      high-throughput sequencing has been established and used to analyze miRNA
      expression profiles. This study showed that 39 miRNAs were related to RLR through
      the analysis of miRNA high-throughput sequencing. Their role toward rat normal
      hepatocyte line BRL-3A was studied by gain- and loss-of-function analyses, and
      one of them, microRNA-21 (miR-21), obviously upregulated and promoted BRL-3A cell
      proliferation. Using bioinformatics to search for miR-21 targets revealed that
      Fas ligand (FASLG) is one of miR-21's target genes. A dual-luciferase report
      assay and Western blot assay showed that miR-21 directly targeted the 3'
      untranslated region of FASLG and inhibited the expression of FASLG, which
      suggests that miR-21 promoted BRL-3A cell proliferation by reducing FASLG
      expression. 

PMID- 25966188
TI  - Association of methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with
      ischemic stroke in the Eastern Chinese Han population.
AB  - The association between the MTHFR genetic polymorphism and ischemic stroke has
      been reported by a number of investigators. However, the results have been
      controversial and conflicting. The aim of this study was to explore the
      association between the MTHFR variants C677T and A1298C and the risk of ischemic
      stroke in an Eastern Chinese Han population. A total of 199 patients with
      ischemic stroke and 241 controls were recruited. Genotyping of the MTHFR C677T
      and A1298C polymorphisms was carried out using the Taqman 7900HT Sequence
      Detection System. The overall estimates (odds ratio: OR) for the allele (C) and
      genotype (AC+CC) of the A1298C polymorphism were 1.57 [95% confidence interval
      (CI) = 1.16-2.10], and 2.36 (95%CI = 1.39-4.00), respectively, establishing
      significant association of the MTHFR A1298C polymorphism with ischemic stroke. In
      contrast, there were no statistically significant differences compared to
      controls between MTHFR C677T polymorphic variants in the association ischemic
      stroke risk. Furthermore, haplotype-based analysis demonstrated that compared
      with the C-677-A-1298 haplotype, the C-677-C-1298 and T-677-C-1298 haplotypes
      showed significant increased risk of ischemic stroke (OR = 1.56; 95%CI = 1.07-
      2.2; P = 0.02; OR = 1.76; 95%CI = 1.17-2.65; P < 0.01, respectively). We
      concluded that the A1298C polymorphism and the haplotypes C-677-C-1298 and T-677
      C-1298 in MTHFR might modulate the risk of ischemic stroke in the Eastern Chinese
      Han population. 

PMID- 25966190
TI  - Genetic diversity and differentiation in Prunus species (Rosaceae) using
      chloroplast and mitochondrial DNA CAPS markers.
AB  - Chloroplast (cpDNA) and mitochondrial DNA (mtDNA) were analyzed to establish
      genetic relationships among Tunisian plum cultivars using the polymerase chain
      reaction restriction fragment length polymorphism (PCR-RFLP) technique. Two mtDNA
      regions (nad 1 b/c and nad 4 1/2) and a cpDNA region (trnL-trnF) were amplified
      and digested using restriction enzymes. Seventy and six polymorphic sites were
      revealed in cpDNA and mtDNA, respectively. As a consequence, cpDNA appears to be
      more polymorphic than mtDNA. The unweighted pair group method with arithmetic
      mean (UPGMA) dendrogram showed that accessions were distributed independently of
      their geographical origin, and introduced and local cultivars appear to be
      closely related. Both UPGMA and principal component analysis grouped Tunisian
      plum accessions into similar clusters. The analysis of the pooled sequences
      allowed the detection of 17 chlorotypes and 12 mitotypes. The unique haplotypes
      detected for cultivars are valuable for management and preservation of the plum
      local resources. From this study, PCR-RFLP analysis appears to be a useful
      approach to detect and identify cytoplasmic variation in plum trees. Our results
      also provide useful information for the management of genetic resources and to
      establish a program to improve the genetic resources available for plums. 

PMID- 25966189
TI  - Plasma exchange parameter selection and safety observation of children with
      severe ricinism.
AB  - The aim of this study was to investigate the selection of plasma exchange (PE)
      parameters and the safety of children with severe ricinism. The PE parameters and
      heparin dosage in 7 children with severe ricinism were recorded, and changes in
      the patients' vital signs and coagulation function were monitored before and
      after PE. All patients successfully completed PE. The speed of blood flow was 50
      80 mL/min, speed of exchange flow was 600-800 mL/h, and isolating rate of blood
      plasma was 12.5-19.05%. Transmembrane pressure was stable at approximately 100
      mmHg, and venous pressure was stable at approximately 95 mmHg. The first dose of
      heparin was 0.39 +/- 0.04 mg/kg, and the maintaining heparin dose was 0.40 +/-
      0.05 to 0.22 +/- 0.03 mg.kg(-1).h(-1). During the PE process, mean arterial
      pressure, heart rate, respiratory rate, and pulse oxygen saturation were steady.
      After PE, the activated partial thromboplastin time and thrombin time prolonged
      to 2-3 times greater than that before PE. However, no bleeding tendency was seen.
      For children with severe ricinism, the choice of PE to eliminate the toxin from
      blood, tissues, and organs was safe and effective.

PMID- 25966191
TI  - Muscle pain, fever, cough, and progressive dyspnea in a woman with eosinophilic
      pneumonia.
AB  - The diagnosis of eosinophilic pneumonia (EP) is rare and challenging. This
      condition is frequently misdiagnosed as pulmonary tuberculosis, lymphoma,
      schistosomiasis, Wegener's granuloma, severe acute respiratory syndrome, or
      severe community-acquired pneumonia. Herein, we report a case in which computed
      tomography (CT)-guided percutaneous lung biopsy was used to diagnose EP without
      alveolar eosinophilia or peripheral eosinophilia. A roundworm identified in the
      patient's stool confirmed the precise diagnosis to be parasitic EP. This is, to
      our knowledge, the first reported case of EP confirmed by CT-guided percutaneous
      lung biopsy. CT-guided percutaneous lung biopsy may represent a new tool for the
      diagnosis of EP in patients without typical alveolar eosinophilia or peripheral
      eosinophilia. 

PMID- 25966192
TI  - Chromosome stickiness impairs meiosis and influences reproductive success in
      Panicum maximum (Poaceae) hybrid plants.
AB  - Chromosome stickiness has been studied in several species of higher plants and is
      characterized by sticky clumps of chromatin resulting in sterility. Chromosome
      stickiness was recorded in Panicum maximum hybrid plants that were cultivated in
      the field. In the meiocytes affected, chromosomes clumped into amorphous masses
      that did not orient themselves on the equatorial plate, and anaphase I
      disjunction failed to occur. After a normal cytokinesis, the masses of chromatin
      were divided between both daughter cells. Metaphase and anaphase of the second
      division also did not occur, and after the second cytokinesis, polyads were
      formed. This abnormality arose spontaneously. Abnormalities that cause male
      sterility are an important tool for obtaining hybrid seeds in plant breeding.
      This is the first report of an abnormality affecting pollen viability in P.
      maximum. This finding can open a new opportunity in the breeding program of this
      species that is devoted to hybridization where manual cross-pollination is
      difficult and time consuming. 

PMID- 25966193
TI  - Acute toxic effects of sonodynamic therapy on hypertrophic scar fibroblasts of
      rabbit ears.
AB  - The objective of this study was to observe the acute cytotoxic effects of
      hematoporphyrin monomethyl ether sonodynamic therapy (HMME-SDT) on hypertrophic
      scar fibroblasts of rabbit ears. We first assessed the effects of different
      irradiation times and HMME concentrations on the survival of hypertrophic scar
      fibroblasts using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assay to determine the optimum irradiation time and HMME
      concentration. The hypertrophic scar fibroblast cell suspensions of the rabbit
      ears were divided into four groups, the survival rates were detected using the
      MTT assay, and the type of cell death was detected by Annexin V/propidium iodide
      (PI) double staining flow cytometry. Our results showed that HMME-SDT
      significantly reduced the viability of hypertrophic scar fibroblasts of rabbit
      ears at ultrasonic irradiation times of 30, 60, and 90 s, but not 10 s (P <
      0.05). HMME alone had no significant effect on the cell survival rate at any
      irradiation time (P > 0.05). In contrast, the cell survival rate was
      significantly decreased at an irradiation time of 10 s and HMME concentrations of
      20 and 50 MUg/mL (P < 0.05). Furthermore, Annexin V/PI double staining showed
      necrosis and apoptosis of the hypertrophic scar fibroblasts. Given our results,
      HMME might be an effective sound-sensitive agent for SDT as it has a significant
      lethal effect on hypertrophic scar fibroblasts of rabbit ear cultured in vitro.
      HMME-SDT may therefore provide a new method for the treatment of hypertrophic
      scar formation. 

PMID- 25966194
TI  - Structural modeling and analysis of dengue-mediated inhibition of interferon
      signaling pathway.
AB  - Dengue virus (DENV) belongs to the family Flaviviridae and can cause major health
      problems worldwide, including dengue fever and dengue shock syndrome. DENV
      replicon in human cells inhibits interferon alpha and beta with the help of its
      non-structural proteins. Non-structural protein 5 (NS5) of DENV is responsible
      for the proteasome-mediated degradation of signal transducer and activator of
      transcription (STAT) 2 protein, which has been implicated in the development of
      resistance against interferon-mediated antiviral effect. This degradation of
      STAT2 primarily occurs with the help of E3 ubiquitin ligases. Seven in absentia
      homologue (SIAH) 2 is a host protein that can mediate the ubiquitination of
      proteins and is known for its interaction with NS5. In this study, comprehensive
      computational analysis was performed to characterize the protein-protein
      interactions between NS5, SIAH2, and STAT2 to gain insight into the residues and
      sites of interaction between these proteins. The objective of the study was to
      structurally characterize the NS5-STAT2, SIAH2-STAT2, and NS5-SIAH2 interactions
      along with the determination of the possible reaction pattern for the degradation
      of STAT2. Docking and physicochemical studies indicated that DENV NS5 may first
      interact with the host SIAH2, which can then proceed towards binding with STAT2
      from the side of SIAH2. These implications are reported for the first time and
      require validation by wet-lab studies.

PMID- 25966195
TI  - An efficient algorithm for computing fixed length attractors based on bounded
      model checking in synchronous Boolean networks with biochemical applications.
AB  - Genetic regulatory networks are the key to understanding biochemical systems. One
      condition of the genetic regulatory network under different living environments
      can be modeled as a synchronous Boolean network. The attractors of these Boolean
      networks will help biologists to identify determinant and stable factors.
      Existing methods identify attractors based on a random initial state or the
      entire state simultaneously. They cannot identify the fixed length attractors
      directly. The complexity of including time increases exponentially with respect
      to the attractor number and length of attractors. This study used the bounded
      model checking to quickly locate fixed length attractors. Based on the SAT
      solver, we propose a new algorithm for efficiently computing the fixed length
      attractors, which is more suitable for large Boolean networks and numerous
      attractors' networks. After comparison using the tool BooleNet, empirical
      experiments involving biochemical systems demonstrated the feasibility and
      efficiency of our approach. 

PMID- 25966196
TI  - Mitochondrial DNA diversity of feral pigs from Karukinka Natural Park, Tierra del
      Fuego Island, Chile.
AB  - Control or eradication of exotic species is one of the greatest challenges facing
      biodiversity and ecosystem conservation. Domestic pigs (Sus scrofa domestica)
      were released and became feral in the southern region of Chilean Tierra del Fuego
      Island in the 1900s. Currently, they inhabit part of Karukinka Natural Park, an
      area of global conservation concern. To gain insight into the control of this
      invasive species, we analyzed genetic variation in the mitochondrial DNA control
      region to determine the origin and population subdivision of feral pigs in Tierra
      del Fuego. Sequences from a sample of 42 feral pigs, 10 domestic pigs from local
      farms, and references from other countries and commercial breeds revealed 2
      highly differentiated populations, 1 in the western and the other in the eastern
      area of the park, each harboring a different haplotype, suggesting no
      connectivity between populations. Comparison of these haplotypes with reference
      sequences from other countries and commercial breeds indicated that feral pigs
      from Chilean Tierra del Fuego are of European origin, very likely from 2 separate
      introduction events. The haplotype found in the western feral population was also
      identified in domestic pigs from a farm. This raises concerns regarding the
      possible connectivity between stocks from local farms and the wild population.
      Based on these results, we recommend the development of strategies for
      controlling the population of this invasive species in Karukinka Natural Park. 

PMID- 25966197
TI  - Influence of cyclophilin D protein expression level on endothelial cell oxidative
      damage resistance.
AB  - We examined the influence of cyclophilin-D (CypD) protein expression level on
      endothelial cell oxidative damage resistance. A model of CypD protein expression
      or high expression in endothelial cells was established through gene silencing or
      cloning. The comparable groups were normal endothelial cells cultured in
      phosphate-buffered solution in liquid handling cells containing 500 mM H2O2 for
      90 or 120 min, and then the medium was replaced with common nutrient solution and
      cultured again for 24 h. The apoptosis rate and nitric oxide (NO) levels of each
      group were tested. The cell apoptosis rate of the CyPD low expression group
      (32.51 +/- 6.6 %) was significantly lower than that of the control group (52.57
      +/- 5.84%, P = 0.001), and total NO production was 24.06 +/- 3 and 13.03 +/- 3.55
      MUM. The apoptosis rate of the CyPD high expression group (24.24 + 3.08%) was
      significantly higher than that of the control group (7.7 + 0.68%, P < 0.001);
      total NO production was 3.55 +/- 1.53 and 8.46 +/- 0.77 MUM, which was
      significantly different (P = 0.008). CypD protein could increase oxidative stress
      and cause endothelial cell injury and apoptosis. 

PMID- 25966198
TI  - Study of the relationship between the expression of nerve growth factor and
      aneurysm formation and prognosis.
AB  - We sought to investigate the effect of nerve growth factor (NGF) expression on
      the formation and prognosis of cerebral aneurysms. Forty-eight cases were
      selected following a diagnosis of cerebral aneurysm using computed tomography
      angiography and surgical confirmation. Thirty-four cases of healthy deaths were
      also chosen. The tissue was tested for NGF expression changes by reverse
      transcription PCR, Western blot and histopathology, and NGF expression was
      compared between the cerebral aneurysm and healthy groups. The expression level
      of NGF in cerebral aneurysm tissue was significantly increased over that observed
      in control tissue. The abnormal expression of NGF is related to cerebral
      aneurysms. The elevated expression of NGF in cerebral aneurysms may be associated
      with a poor prognosis. 

PMID- 25966199
TI  - Relationship between abnormal NOS expression and the pathogenesis of cerebral
      aneurysm.
AB  - We sought to investigate the relationship between abnormal expression of nitric
      oxide synthase (NOS) and pathogenesis of cerebral aneurysm. Brain tissues were
      collected from 36 patients with cerebral aneurysm confirmed by computer
      tomography with angiography or neurosurgical therapy. The control group consisted
      of 25 patients of similar age who had no vascular diseases, as confirmed by
      magnetic resonance imaging. Samples of cortical arterioles were collected. The
      structure of the aneurysms was detected by hematoxylin and eosin staining, and
      the expression of inducible NOS was detected by immunohistochemistry. NOS
      expression was significantly higher in the patient group than in the control
      group (patients: 30/36 strongly positive; control: 0/25 strongly positive; P <
      0.05). In conclusion, the pathogenesis underlying cerebral aneurysm may be due to
      abnormal expression of NOS, degradation of the extracellular matrix, aggravation
      of a pro-inflammatory reaction, or a deficiency in arterial elasticity layer
      synthesis. These changes may result in a deficiency in vascular remodeling. 

PMID- 25966200
TI  - Correlation between p53 and epidermal growth factor receptor expression in breast
      cancer classification.
AB  - This study aimed to explore new opportunities for developing targeted therapy for
      triple-negative breast cancer (TNBC) by analyzing the significance and
      association between p53 and epidermal growth factor receptor (EGFR) expression in
      different molecular subtypes of breast cancer. The clinical and pathological data
      of 264 patients with breast cancer receiving surgery in our hospital from January
      2012 to August 2013 were retrospectively analyzed. According to the expression of
      estrogen receptor, progesterone receptor, human epidermal growth factor receptor
      2 (HER2), Ki-67, CK5/6, p53, and EGFR detected by immunohistochemical methods,
      breast cancer was divided into four molecular subtypes. Then, the expression of
      p53 and EGFR as well as their correlation in the different subtypes were
      determined. Among the four subtypes, luminal B breast cancer was the most common
      type. TNBC and HER2-enriched breast cancer had larger tumor sizes with higher
      expression of Ki-67 as compared with the luminal types. TNBC had a lower lymph
      node metastasis rate but higher CK5/6 and EGFR expression than the other three
      types. The expression of p53 was higher in luminal B, HER2-enriched, and triple
      negative breast cancers, and this was positively correlated with the expression
      of EGFR in TNBC but not in the other subtypes. p53 and EGFR expression was
      positively correlated in TNBC, which enables us to explore the molecular
      biological characteristics of TNBC, so as to provide new ideas for the treatment
      of TNBC. 

PMID- 25966201
TI  - Ultrasonic imaging of gunshot wounds in pig limb.
AB  - We investigated wound tract extension of traumatic gunshot wounds in limb soft
      tissues as well as wound tract sonographic features and change-patterns when the
      limb position was changed. The experimental animals included 8 healthy crossbred
      pigs in the Chengdu plain region. Chinese Type 53 Carbine was used to establish
      the gunshot wound model of porcine soft tissues. Gunshot-injured zones in the
      soft tissues were dynamically observed at different time points using ultrasonic
      technology. Pathological examinations were performed for the corresponding
      regions for comparison and analysis. The internal echo of the wound tract was a
      pipe-like echo that changed over time. The wound tract extension changed with
      postural changes. The gas echo extended along the inside of the wound track,
      surrounding the fascia to further tissues. Ultrasonic imaging of gunshot wounds
      in pig soft tissues shows specific characteristics. The application of ultrasound
      technology may provide important imaging protection for gunshot wound debridement
      and postoperative unobstructed drainage, helping to improve the judgment and
      treatment of limb gunshot injuries. 

PMID- 25966202
TI  - Distribution of forensic marker allelic frequencies in Pernambuco, Northestern
      Brazil.
AB  - Pernambuco is one of the 27 federal units of Brazil, ranking seventh in the
      number of inhabitants. We examined the allele frequencies of 13 short tandem
      repeat loci (CFS1PO, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51,
      D21S11, FGA, TH01, vWA, and TPOX), the minimum recommended by the Federal Bureau
      of Investigation and commonly used in forensic genetics laboratories in Brazil,
      in a sample of 609 unrelated individuals from all geographic regions of
      Pernambuco. The allele frequencies ranged from 5 to 47.2%. No significant
      differences for any loci analyzed were observed compared with other publications
      in other various regions of Brazil. Most of the markers observed were in Hardy
      Weinberg equilibrium. The occurrence of the allele 47.2 (locus FGA) and alleles
      35.1 and 39 (locus D21S11), also described in a single study of the Brazilian
      population, was observed. The other forensic parameters analyzed (matching
      probability, power of discrimination, polymorphic information content, paternity
      exclusion, complement factor I, observed heterozygosity, expected heterozygosity)
      indicated that the studied markers are very informative for human forensic
      identification purposes in the Pernambuco population.

PMID- 25966203
TI  - Association of CD14 C159T polymorphism with atopic asthma susceptibility in
      children from Southeastern China: a case-control study.
AB  - CD14 is involved in primary immune and inflammatory responses. The -159 C/T
      variation in the CD14 gene plays an important role in regulating CD14 expression
      and has been associated with the susceptibility to various diseases, including
      allergies. In this study, we examined the association between the C-159T
      polymorphism and atopic asthma susceptibility in children from Southeastern
      China. The study population included 746 unrelated children of Chinese Han
      nationality (362 patients with atopic asthma and 384 healthy controls). CD14 gene
      polymorphisms were identified by direct sequencing of polymerase chain reaction
      products. Total immunoglobulin E (IgE) levels in human serum samples were
      determined using an enzyme-linked immunosorbent assay. Individuals carrying the
      TT genotypes for rs2569190 were significantly associated with an increased risk
      of atopic asthma compared with those carrying the wild-type homozygous CC
      genotypes [adjusted odds ratio (OR) by gender and age, from 1.075-2.398, P =
      0.025]. Total serum IgE levels in TT genotype carriers were significantly higher
      than those in CC genotype carriers in atopic asthma patients (286.3 +/- 161.5
      IU/mL vs 248.3 +/- 147.8 IU/mL). Our data suggest that the CD14 TT genotype may
      be a genetic susceptibility marker for atopic asthma in Chinese Han children. 

PMID- 25966204
TI  - Molecular cloning and expression analysis of female sterile homeotic gene (fsh)
      in the oriental river prawn Macrobrachium nipponense.
AB  - The gene female sterile homeotic (fsh) plays crucial roles in molecular function,
      including protein kinase activity and DNA binding, which are involved in
      biological processes such as terminal region determination and negative
      regulation of DNA-dependent transcription. Although fsh has been found in
      Drosophila melanogaster, little is known regarding its expression in crustaceans.
      In this study, a fsh gene homologue, designated as Mnfsh, was cloned and
      characterized from the testis of the oriental river prawn, Macrobrachium
      nipponense, by using EST analysis and the RACE approach for the first time. The
      full-length cDNA of Mnfsh was 2029 bp, consisting of a 5' UTR of 361 bp, a 3' UTR
      of 216 bp, and an ORF of 1452 bp encoding 484 amino acids. qRT-PCR analysis
      showed that the Mnfsh gene was expressed in the testis, ovary, muscle, heart,
      eyestalk, and abdominal ganglion, with the highest level of expression in the
      ovary and the lowest in the heart. qRT-PCR analyses showed that the expression
      levels of Mnfsh mRNA both significantly increased in the zoea stage, the VII
      larvae, and 1st day post-larvae after metamorphosis. In conclusion, the results
      of the present study indicate that Mnfsh is an arthropod fsh homologue and
      probably also plays important roles in embryogenesis, organogenesis, and
      morphological differentiation of M. nipponense. 

PMID- 25966205
TI  - Deciphering the spectrum of somatic mutations in the entire mitochondrial DNA
      genome.
AB  - The mitochondrion is a crucial intracellular organelle responsible for regulating
      cellular energy metabolism, producing free radicals, initiating and executing the
      apoptotic pathways. Previous studies have shown that somatic mutations in
      mitochondrial DNA are associated with various tumors, which may be involved
      during carcinogenesis and tumor progression. To examine the mutation pattern in
      cancer, 625 reported somatic mutations in the mitochondrial DNA genome were
      analyzed. We found that, except for deletions and insertions, most somatic
      mutations were point mutations, accounting for 89.44% of somatic mutations.
      Transition was the predominant form of somatic mutation in the entire
      mitochondrial DNA genome, accounting for 87.12% of point mutations, most of which
      were homoplastic. Frequency statistics analysis of point mutations indicated
      that, except for 3 tRNA genes, the mutations were distributed on all resting
      genes and in the D-loop region, with the latter showing the highest frequency of
      somatic mutation (19.34%), followed by the tRNA leucine 2 gene and non-coding
      regions between base pairs 5892 and 5903, while 13 coding-region genes and 2 rRNA
      genes showed a relatively lower frequency of somatic point mutations.
      Nonsynonymous mutations and terminal amino acid changes were the primary point
      somatic mutations detected from 13 coding-region genes, which may cause
      mitochondrial dysfunction in cancer cells. We found that the somatic mutations
      may affect the mitochondrial DNA genome; the non-coding region should be examined
      to identify somatic mutations as potential diagnostic biomarkers for early
      detection of cancer. 

PMID- 25966206
TI  - Relation between prognosis and changes of MBP and S100B in premature infants with
      periventricular leukomalacia.
AB  - This study aims to explore the relation between changes in myelin basic protein
      (MBP) and S100 protein (S100B) serum levels and prognosis in premature infants
      with periventricular leukomalacia (PVL). In our hospital, 78 premature infants
      with PVL and 43 normal premature infants were studied from July 1, 2007 to
      December 31, 2008. MBP and S100B serum levels were detected at 1, 3, 7, and 14
      days after birth by using enzyme-linked immunosorbent assay. All infants were
      followed four times (once every 3 months) after discharge from hospital. Their
      intelligence quotient and physical development index were tested by using Gesell
      developmental scales. The MBP serum levels were significantly higher in premature
      infants with PVL at any time point than in normal premature infants. S100B serum
      levels gradually increased at 1, 3, and 7 days; peaked on the 7th day; and then
      gradually decreased to the normal level on the 14th day. The intelligence
      quatient and physical development index of infants with increased S100B and MBP
      levels on the 7th day were lower than those of infants who had normal S100B and
      MBP levels and those of normal premature infants. A negative relation exists
      between S100B and MBP serum levels and prognosis in PVL infants. An increase of
      MBP and S100B levels lasting >7 days could cause poor prognosis. 

PMID- 25966207
TI  - Effect of ulinastatin on HMGB1 expression in rats with acute lung injury induced
      by sepsis.
AB  - The aim of this study was to investigate the influence of ulinastatin (UTI) on
      high mobility group box 1 (HMGB1), tumor necrosis factor (TNF)-alpha, and
      interleukin (IL)-6 expression in acute lung injury (ALI) rats with sepsis caused
      by cecal ligation and puncture (CLP) surgery, as well as to examine the
      underlying biological mechanism. Thirty rats were randomly and evenly divided
      into sham (control), CLP, and CLP + UTI groups. Thirty minutes after the surgery,
      the rats in the CLP + UTI group received UTI via the caudal vein, while normal
      saline was administered to rats in the other groups. Blood, lung tissues, and
      bronchoalveolar lavage fluid (BALF) were collected at different time points (6,
      12, 24, and 48 h) after surgery for determination of related indicators. Compared
      with the CLP group, rats in the CLP + UTI group exhibited higher seven day
      survival rates, less lung injury, and decreased HMGB1 expression in the lung
      tissue, serum, and BALF. In addition, the levels of TNF-alpha and IL-6 at 24 h in
      the CLP + UTI group were markedly lower than those in the CLP group. These
      results suggest that by deregulation, UTI might decrease the lung injury and
      increase the survival time of ALI rats by downregulating HMGB1 expression as well
      as by inhibiting TNF-alpha and IL-6 levels in serum and BALF. 

PMID- 25966208
TI  - Effect of polymorphisms of vascular endothelial growth factor on prognosis in
      osteosarcoma patients.
AB  - We investigated the association between vascular endothelial growth factor (VEGF)
      gene +1612G/A, -634C/G, and +936G/C and the clinical outcome of osteosarcoma.
      Genomic DNA was isolated from blood samples, and 3 VEGF gene polymorphisms
      (+1612G/A, -634C/G, and +936G/C) were analyzed using polymerase chain reaction
      restriction fragment length polymorphism. Of the 194 patients, 82 patients
      (42.27%) showed a good response to chemotherapy, while 73 (37.63%) died during
      the follow-up period. When comparing good and poor responders, we observed no
      significant association between the VEGF +1612G/A, -634G/C, and +936T/C
      polymorphisms and clinical outcome of osteosarcoma patients. According to Cox
      regression analysis, the VEGF +1612A/G, -634G/C, and +936T/C polymorphisms did
      not statistically significantly increase the risk of overall survival of patients
      with osteosarcoma. This study showed that VEGF +1612A/G, -634G/C, and +936T/C
      polymorphisms were not related to the response to chemotherapy and clinical
      outcome of osteosarcoma patients. 

PMID- 25966209
TI  - Malondialdehyde and SOD-induced changes of gastric tissues in acute gastric
      mucosal injury under positive acceleration.
AB  - The aim of this study was to investigate the impacts of positive acceleration
      (+Gz) on the gastric mucosal tissues in cases of acute gastric mucosal injury and
      to explore the role of oxygen free radicals. Thirty Sprague Dawley rats were
      randomly divided into the absolute ethanol control group (A group), absolute
      ethanol +5Gz group (B group), absolute ethanol +10Gz group (C group). Following
      centrifugation, the gastric tissues of each group were studied for the presence
      of gastric mucosal injuries and morphological changes. The concentrations of
      malondialdehyde (MDA) and superoxide dismutase (SOD) contents were simultaneously
      investigated. Degree of gastric mucosal injuries were as follows: C group
      (visually 49.080 +/- 10.254, under light microscopy 9.400 +/- 2.011) > B group
      (visually 23.654 +/- 9.678, under light microscopy 5.000 +/- 1.054) > A group
      (visually 11.410 +/- 3.742, under light microscopy 3.800 +/- 1.399). The gastric
      mucosal MDA content (0.376 +/- 0.084 vs 0.235 +/- 0.044) was significantly higher
      in the C group than in the A group, whereas the SOD content (8.852 +/- 1.001 vs
      10.694 +/- 0.965) was lower than that in the A group. However, the MDA and SOD
      contents did not change much in the B group. Our results suggest that the +Gz
      exposure might aggravate the acute gastric mucosal injury, and changes in MDA and
      SOD contents in the gastric tissues indicated that the oxygen free radicals play
      an important role in this regard. 

PMID- 25966210
TI  - Screening of molecular markers linked to dwarf trait in crape myrtle by bulked
      segregant analysis.
AB  - Plant height is one of the most important traits of plant architecture as it
      modulates both economic and ornamental values. Crape myrtle (Lagerstroemia indica
      L.) is a popular ornamental woody plant because of its long-lasting mid-summer
      bloom, rich colors, and diversified plant architecture. These traits also make it
      an ideal model of woody species for genetic analysis of many ornamental traits.
      To understand the inheritance of plant height and screen for genes modulating
      plant height in Lagerstroemia, segregation of the plant height trait was analyzed
      using the F1 population of L. fauriei (standard) x L. indica 'Pocomoke' (dwarf)
      with 96 seedlings, while dwarf genes were screened using the bulked segregant
      analysis method, combined with 28 amplified fragment length polymorphism primers
      and 41 simple sequence repeat primers. The results showed that the dwarf trait of
      crape myrtle was controlled by a major gene and modified by minor genes. An
      amplified fragment length polymorphism marker, M53E39-92, which was 23.33 cM from
      the loci controlling the dwarf trait, was screened. These results provide basic
      information for marker-assisted selection in Lagerstromia and cloning of dwarf
      genes in future studies. 

PMID- 25966211
TI  - Establishment of a prediction model for the miRNA-based heading date
      characteristics of rice in the booting stage.
AB  - Rice (Oryza sativa L.) is one of the most important food crops in the world. In
      Taiwan, due to the warm climate, there are two harvests annually. However, the
      yield and quality of rice can vary between each crop season in any given year.
      Previous reports have shown that microRNAs (miRNAs) play a crucial role in many
      developmental and physiological processes in plants. In this study, the heading
      date characteristics of 167 rice cultivars from the second crop season were
      recorded, and 27 rice cultivars were selected for preliminary microarray
      analysis. A total of 14 miRNAs from different heading date characteristics in 21
      cultivars were selected based on significant differences in their expression
      profiles. Using a correlation analysis between the heading date and selected
      miRNA expression obtained from real-time polymerase chain reaction (PCR) assays,
      we developed a heading date prediction model. The model includes nine miRNA genes
      with corresponding R2 values of 0.8. To confirm the model, a real-time PCR
      analysis was performed on an additional 27 rice cultivars and we found the model
      predicted the heading date with accuracy. Therefore, the developed prediction may
      be useful in further studies aimed at confirming the reliability of the use of
      miRNA in molecular breeding and to increase the selection efficiency of rice
      cultivars and breeding. 

PMID- 25966212
TI  - Expression and clinical significance of ADAM17 protein in esophageal squamous
      cell carcinoma.
AB  - We examined disintegrin and metalloproteinase 17 (ADAM17) protein expression in
      esophageal squamous cell carcinoma and its clinical and pathological correlated
      factors. Western blotting and immunohistochemistry were used to detect ADAM17
      protein expression in esophageal squamous cell carcinoma and the corresponding
      normal esophageal mucosa in 50 cases. ADAM17 protein expression in 50 cases with
      esophageal squamous cells was 0.887 +/- 0.174; the positive expression rate was
      66% (33/50). ADAM17 protein expression in corresponding normal esophageal mucosa
      was 0.273 +/- 0.081; the positive expression rate was 6% (3/50). Expression in
      esophageal squamous cell carcinoma was significantly higher than that in the
      normal esophageal group (P < 0.01). Esophageal squamous cell ADAM17 protein
      expression and the positive rate were correlated with lymph node metastasis and
      TNM stage (P < 0.05), but not correlated with gender, age, and histological grade
      (P > 0.05). ADAM17 protein was highly expressed in esophageal squamous cell
      carcinoma. This protein may play an important role in the incidence, invasion,
      and metastasis of esophageal cancer and is valuable for the prognosis of patients
      with esophageal cancer.

PMID- 25966213
TI  - Body color development and genetic analysis of hybrid transparent crucian carp
      (Carassius auratus).
AB  - The aim of this study was to investigate the genetic mechanism of the transparent
      trait in transparent crucian carp. We observed body color development in
      transparent crucian carp larvae and analyzed heredity of color in hybrids
      produced with red crucian carp, ornamental carp, and red purse carp. The results
      showed that the body color of the newly hatched larvae matured into the adult
      pattern at approximately 54 days post-hatching. Two inter-species reciprocal
      crosses between transparent crucian carp and red crucian carp, and self-cross F1
      of transparent crucian carp and self-cross F1 of red marking transparent crucian
      carp were conducted, and results indicated that the transparent-scaled trait is
      dominant over the normal-scaled trait. Furthermore, the transparent trait is a
      quantitative trait. All offspring in the four inter-genera reciprocal crosses of
      transparent crucian carp with ornamental carp and red purse carp were hybrids of
      common carp and crucian carp, and had a relatively low survival rate of 10-20%.
      Moreover, the transparent-scaled trait was observed to be dominant over the
      normal-scaled trait in the hybrid fish. In conclusion, our results suggest that
      the genetic mechanism underlying the color of goldfish is complex and requires
      further investigation. 

PMID- 25966214
TI  - Molecular cloning and expression analysis of TRAF3 in chicken.
AB  - Tumor necrosis factor receptor-associated factor 3 (TRAF3) is a crucial regulator
      that suppresses c-Jun N-terminal kinase and non-canonical nuclear factor-kB
      signaling, but facilitates type I interferon production. To determine TRAF3
      function in innate immune responses among birds, particularly chicken, we cloned
      and characterized the chicken TRAF3 gene (chTRAF3) and detected its tissue
      expression profile in chicken. We also detected the differential expression of
      chTRAF3 and its downstream gene interferon-beta (IFN-beta) upon different stimuli
      in primary chicken embryo fibroblast cells. Two chTRAF3 gene products, chTRAF3-1
      and chTRAF3-2, can be produced by alternative splicing. The full-length coding
      sequence of chTRAF3 (chTRAF3-1) was 1704 base pairs and encoded a protein of 567
      amino acids with high identity to TRAF3 homologs from mammals and other birds.
      The deduced amino acid sequence showed typical characteristics of TRAFs, with a
      RING finger domain, 2 zf-TRAF motifs, and a MATH domain. Quantitative real-time
      polymerase chain reaction analysis revealed broad expression of chTRAF3 in all
      detected tissues, with abundant expression in the spleen, thymus, lung, and small
      intestine. Expression of chTRAF3 was significantly upregulated in a time- and
      concentration-dependent manner in chicken embryo fibroblast cells challenged with
      poly I:C or poly dA-dT. Furthermore, chTRAF3 and IFN-beta mRNA expression from
      chicken embryo fibroblast cells challenged with Newcastle disease virus F48E9
      suffered intense suppression compared with Newcastle disease virus Mukteswar
      infection. Our results indicate that chTRAF3 plays important roles in defending
      against both RNA and DNA virus infection. 

PMID- 25966215
TI  - Characterization and expression of DDX6 during gametogenesis in the Chinese
      mitten crab Eriocheir sinensis.
AB  - DDX6 belongs to a family of DEAD-box RNA helicases, which are RNA splicing
      proteins that ensure the correct folding and structure of mature RNA.
      Gametogenesis requires the participation of many kinds of RNA. To explore its
      functions during Eriocheir sinensis gametogenesis, we cloned a full-length DDX6
      cDNA sequence from E. sinensis (Es-DDX6) which contains a 1536-nucleotide open
      reading frame encoding a 512-amino acid protein. Multiple sequence alignments
      showed that Es-DDX6 has ten conservative DEAD-box family motifs. Tissue
      expression analysis of Es-DDX6 mRNA and protein levels showed that Es-DDX6 was
      highly expressed in both the ovary and testis. qRT-PCR analysis revealed the
      widespread expression of Es-DDX6 mRNA during various stages of gonad development
      peaking in October. In addition, immunohistochemical studies showed that oocytes
      and the spermatogonium and primary spermatocytes of testes contained high levels
      of cytoplasmic Es-DDX6 and decreased expression levels in spermatids.
      Interestingly, there was no expression of Es-DDX6 in these cells as they matured
      along the male reproductive system. Since oocytes and spermatocytes are active in
      meiosis and oocytes undergo rapid growth in October, these results provide
      preliminary evidence that Es-DDX6 plays a role in E. sinensis gametogenesis and
      oocyte growth processes. 

PMID- 25966216
TI  - Analysis of genetic diversity of salt-tolerant alfalfa germplasms.
AB  - Random amplified polymorphic DNA technology was used to analyze the genetic
      diversity of 25 salt-tolerant alfalfa varieties using 30 different primers.
      Results showed that the percentage of polymorphic loci between single-plant DNA
      was 81.52%, and that between mixed DNA of various varieties was 61.65%. Compared
      to the mixed DNA samples, single-plant DNA samples can better reveal the level of
      genetic variation among and between alfalfa varieties. The gene differentiation
      coefficients of 18 Chinese salt-tolerant alfalfa varieties and 7 American salt
      tolerant alfalfa varieties were 0.271 and 0.152, respectively, showing that the
      exchange of genes between Chinese salt-tolerant alfalfa germplasms was more
      frequent than that of American germplasms. As a topical cross-pollinated plant,
      the genetic structure of biological populations of alfalfa was directly linked to
      its breeding system. According to the analysis of genetic distance (GD), 25
      varieties can be divided into 9 groups, among which, the GD of Tumu No. 1 and
      Tumu No. 2 was the shortest (0.148), and the GD of Jieda No. 1 and Tumu was the
      longest (0.786). The analysis of genetic diversity of salt-tolerant alfalfa
      germplasms provided a theoretical basis for the creation of an alfalfa salt
      tolerant core germplasm repository and for the selection and breeding of new salt
      tolerant varieties. 

PMID- 25966217
TI  - Characterization of MUSTN1 gene and its relationship with skeletal muscle
      development at postnatal stages in Pekin ducks.
AB  - Musculoskeletal embryonic nuclear protein 1 (MUSTN1) gene is involved in myogenic
      fusion and differentiation in rats. We previously showed the differential
      expression of MUSTN1 in week (W) 2 and W6 breast muscles of Pekin ducks. In this
      study, we further investigated its molecular characteristics and expression
      profiles in different tissues at W7 and in breast and leg muscles at W1, W3, W5,
      W7, and W9. The relationship between muscle development and muscle fiber areas
      was also investigated. A 358-bp cDNA sequence was obtained. The coding sequence
      of duck MUSTN1 cDNA encoded a 78-amino acid sequence, which showed high
      similarity with those of other species (96% similarity with zebra finch and 94%
      with chicken). In addition, a 6435-bp genomic DNA sequence of MUSTN1 was
      obtained. In total, 231 transcription factor-binding sites were found in the
      promoter region, and many of these transcription factors were involved in the
      regulation of muscle development. MUSTN1 expression in breast muscle increased
      from W1 to W5 and then decreased at W9. In leg muscle, the expression increased
      from W1 to W3 and then decreased. The relative growth rates of breast and leg
      muscle fibers reached their peaks at W3-W5 and W1-W3, respectively. Since the
      greatest relative growth rates appeared at the highest expression levels of the
      MUSTN1 gene, it was thought to play roles in duck muscle development. Our
      findings would be helpful in understanding the molecular characteristics and
      functions of the MUSTN1 gene in breast muscle development of ducks. 

PMID- 25966218
TI  - TGF-beta1 polymorphism 509 C>T is associated with an increased risk for
      hepatocellular carcinoma in HCV-infected patients.
AB  - Transforming growth factor-beta 1 (TGF-beta1), a member of the transforming
      growth factor beta family, functions as a multi-functional cytokine and plays a
      key role in cellular growth, proliferation, and differentiation. The 509 C/T
      polymorphism in the TGF-beta1 gene has been implicated in the outcome of
      hepatitis C virus (HCV) infection; however, little is known regarding the
      relationship between TGF-beta1 gene mutations and the development of
      hepatocellular carcinoma (HCC) in HCV-infected patients. The aim of the study was
      to evaluate the effect of the TGF-beta1 polymorphisms 509 C>T on the occurrence
      of HCC in patients chronically infected with HCV in a Chinese Han population. The
      results showed that HCC patients had a higher frequency of the TGF-beta1 -509 TT
      genotype distribution of the TGF-beta1 -509 polymorphism and a lower frequency of
      the CC genotype. Serum TGF-beta1 levels were significantly higher in patients
      with the TT genotype than in those with the CC genotype. In this study, we
      confirmed that the TGF-beta1 polymorphism 509 C>T is associated with the risk of
      HCC in HCV-infected patients.

PMID- 25966219
TI  - Association of genetic polymorphisms in TERT-CLPTM1L with lung cancer in a
      Chinese population.
AB  - Genome-wide association studies in several ethnic groups have reported that
      polymorphisms of the telomerase reverse transcriptase (TERT) and cleft lip and
      palate transmembrane 1-like (CLPTM1L) genes, located on 5p15.33, are associated
      with susceptibility to lung cancer. However, whether genetic variants of TERT
      CLPTM1L are associated with an increased risk of lung cancer in the Chinese Han
      population is unknown. This study examined associations between five single
      nucleotide polymorphisms (SNPs) of TERT-CLPTM1L (rs402710, rs401681, rs465498,
      rs4975616, and rs2736100) and lung cancer in a Chinese Han population in the
      Hubei Province. The five SNPs were detected using the Sequenom MassArray((r))
      iPLEX System in 304 lung cancer patients and 319 controls. Of the five SNPs,
      rs4975616 did not conform to Hardy-Weinberg equilibrium in the controls. Only
      rs2736100 was significantly (P = 0.034) associated with an increased risk of lung
      cancer. In the linkage disequilibrium analyses, a block of strong linkage
      disequilibrium was observed between rs401681 and rs465498 (D' = 0.986; r(2) =
      0.546). No linkage disequilibrium between rs2736100 and the other three SNPs was
      found. In the haplotype analyses, the frequencies of the TTCT haplotype in
      rs402710, rs401681, rs465498, and rs2736100 differed significantly between case
      and control subjects (odds ratio = 0.56; 95% confidence interval, 0.36-0.88; P =
      0.012). The results of this study suggested that rs2736100 on TERT-CLPTM1L
      indicates a poor prognosis for lung cancer in the Chinese Han population.

PMID- 25966220
TI  - Association of interleukin-1beta -511C/T promoter polymorphism with COPD risk: a
      meta-analysis.
AB  - Studies examining the role of interleukin (IL)-1beta -511C/T promoter
      polymorphism in the pathogenesis of chronic obstructive pulmonary disease (COPD)
      have shown inconsistent results. This meta-analysis was performed to assess the
      association between the IL-1beta-511C/T promoter polymorphism and COPD
      susceptibility. Published case-control, cross-sectional, and cohort studies from
      Pubmed, Embase, and China National Knowledge Infrastructure databases were
      retrieved. Data were extracted and pooled odds ratios (ORs) with 95% confidence
      intervals (CIs) were calculated. Twelve studies with 1692 cases and 2009 controls
      were included in this meta-analysis. Pooled effect size showed an overall but not
      significantly decreased risk of IL-1beta-511 C/T with COPD susceptibility (OR =
      0.89, 95%CI = 0.78-1.01) in a complete overdominant genetic model (TT+CC vs CT),
      indicating that homozygous individuals (CC and TT) have a decreased risk for COPD
      compared with heterozygotes (CT). In subgroup analysis by ethnicity, IL-1beta
      511C/T was significantly correlated with a decreased risk of COPD in Asians (OR =
      0.73, 95%CI = 0.60-0.88, P = 0.001), but not in Caucasians (OR = 1.02, 95%CI =
      0.83- 1.24, P = 0.46), confirming a protective role of IL-1beta-511C/T in COPD in
      Asians. Moreover, after excluding studies that included populations not in Hardy
      Weinberg equilibrium, the pooled results were robust and no publication bias was
      observed. This meta-analysis suggests that the IL-1beta-511C/T promoter
      polymorphism deceases the risk of COPD in Asians. 

PMID- 25966221
TI  - Expression of EpCAM and Wnt/ beta-catenin in human colon cancer.
AB  - The aims of this study were to explore the correlation between the expression of
      EpCAM and the Wnt/beta-catenin pathway in human colon cancer and its clinical
      significance for the evaluation of cancer prognosis. Samples from colon cancer,
      para-carcinoma, or benign intestinal tissue from individual patients (50) and
      from normal intestinal mucosal tissues (20) were obtained from the Pathology
      Department of the Shandong Province Binzhou People's Hospital (Shandong, China).
      Immunohistochemistry was used to detect the expression levels of EpCAM and beta
      catenin proteins in these tissues, and the prognoses of the patients from whom
      the samples were derived were determined on follow-up examination. The
      corresponding in vitro mechanistic siRNA experiments were subsequently performed
      in the human colon cancer cell line HCT116 to observe the regulatory effects of
      silencing EpCAM expression on the Wnt/beta-catenin pathway. From these analyses,
      we determined that the expression levels of EpCAM and beta-catenin were higher in
      cancer tissues compared with other tissues from the same patient, and that the
      expression of EpCAM and Wnt/beta- catenin in colon cancers were positively
      correlated. The prognostic analysis showed an inverse correlation between EpCAM
      and Wnt/beta- catenin expression and patient prognosis. A further examination of
      cellular mechanisms confirmed that the silencing of EpCAM led to decreased
      expression of Wnt/beta-catenin, and thus reduced proliferation and increased the
      apoptosis ratio in the cells. These results suggest that suppression of EpCAM
      might be a new approach for treating colon cancer. 

PMID- 25966222
TI  - beta-asarone from Acorus gramineus alleviates depression by modulating MKP-1.
AB  - In this study, we investigated the antidepressant effects of hippocampal neuron
      administration of beta-asarone, a selective mitogen-activated protein kinase
      phosphatase-1 inhibitor, in a rat model of depression. Our previous studies
      showed that the extracellular signal-regulated kinase signaling pathway and brain
      derived neurotrophic factor expression, which is regulated by extracellular
      signal-regulated kinase, are key links in the biological mechanism of depression.
      Mitogen-activated protein kinase phosphatase-1 (MKP-1) is a negative regulatory
      protein of extracellular signal-regulated kinase signaling pathways. In this
      study, we explored the regulation of MKP-1 by beta-asarone in producing an
      antidepressant effect. 

PMID- 25966223
TI  - A single nucleotide polymorphism in the promoter region of let-7 family is
      associated with lung cancer risk in Chinese.
AB  - Lung cancer is a complex polygenic disease and many genetic factors are involved
      in the development of the disease. As one of the most important and widely
      studied families of microRNA, let-7 appears to play an important role in
      initiation and progression of lung cancer. Any small changes in miRNA level or
      its target point can cause significant changes in gene function. In this study,
      we examined whether a single-nucleotide polymorphism in the promoter region of
      the let-7 family (rs10877887) is associated with the susceptibility to and
      prognosis of lung adenocarcinoma cancer. A hospital-based case-control research
      model was used in our study. The single-nucleotide polymorphism was genotyped in
      69 lung cancer patients and 75 healthy controls by direct sequencing. The
      correlation between rs10877887 genotypes and the susceptibility to lung cancer
      was evaluated using an unconditional logistic regression model. Populations with
      the CT+CC genotype had a significantly increased AC risk compared to those with
      the TT genotype (CT+CC vs TT: P = 0.043, OR = 2.032, 95%CI = 1.018-4.054).
      Furthermore, the risk effect was greater in subgroups of females over 60 years
      old (CT+CC vs TT: OR = 6.857, 95%CI = 1.425-33.008, P = 0.012), and the C allele
      were confirmed to be a risk factor related to lung cancer in these females (P =
      0.012). The single-nucleotide polymorphism rs10877887 in the promoter region of
      the let-7 family was found to be responsible for the susceptibility to lung
      adenocarcinoma cancer in Chinese individuals. This association was significantly
      stronger in females who were more than 60 years old. 

PMID- 25966224
TI  - A novel mutation links to von Hippel-Lindau syndrome in a Chinese family with
      hemangioblastoma.
AB  - Hemangioblastoma of the central nervous system occurs as sporadic tumors or as a
      part of von Hippel-Lindau (VHL) disease, an autosomal dominant hereditary tumor
      syndrome caused by a germline mutation in the VHL tumor suppressor gene. We
      screened a Chinese family with VHL for mutations in the VHL gene and evaluated a
      genetic test for diagnosing VHL disease and clinical screening of family members.
      DNA extracted from the peripheral blood of all live members and from tissue of
      deceased family members with VHL disease was amplified by polymerase chain
      reaction to 3 VHL gene exons. Mutations in the amplification products were
      compared against the Human Gene Mutation Database. The involvement of multiple
      organs among the kindred with VHL disease was confirmed by medical history and
      radiography. Of the 12 members of the 4-generation family, 5 were diagnosed with
      VHL disease. Patient age at the initial diagnosis was 26-36 years (mean = 31
      years). The mean time was 15 (11-19 months) from symptom appearance to the first
      patient visit to the hospital. Sequence analysis revealed that the frameshift
      mutation 327del C (p.Gly39Alafs*26) in exon 1 affected all family members, but
      not the healthy individuals or 16 unrelated controls. Members without gene
      mutation showed no clinical manifestation of VHL disease. We detected a conserved
      novel frameshift mutation in the VHL gene of the family members that contributes
      to VHL. DNA analysis of VHL is advantageous for VHL diagnosis. We developed a
      quick and reliable method for VHL diagnosis.

PMID- 25966225
TI  - Expression of high-mobility group box protein 1 in diabetic foot atherogenesis.
AB  - The role of high mobility group box 1 (HMGB1) has been demonstrated in stroke and
      coronary artery disease but not in peripheral arterial occlusive disease (PAOD).
      The pathogenesis of HMGB1 in acute and chronic vascular injury is also not well
      understood. We hypothesized that HMGB1 induces inflammatory markers in diabetic
      PAOD patients. We studied 36 diabetic patients, including 29 patients with PAOD,
      who had undergone amputation for diabetic foot and 7 nondiabetic patients who had
      undergone amputation after traumatic injury. Expression of HMGB1 and inflammatory
      markers were quantified using immunohistochemical staining. Mitochondrial DNA
      copy number was quantified using real-time polymerase chain reaction. Compared
      with that in the traumatic amputation group, HMGB1 expression in vessels was
      significantly higher in the diabetes and diabetic PAOD groups. In all subjects,
      arterial stenosis grade was positively correlated with the expression levels of
      HMGB1, 8-hydroxyguanosine, malondialdehyde, vascular cell adhesion molecule 1,
      and inflammatory markers CD3, and CD68 in both the intima and the media of
      vessels. Furthermore, HMGB1 expression level was positively correlated with 8
      hydroxyguanosine, vascular cell adhesion molecule 1, nuclear factor-kB, CD3, and
      CD68 expression. Within the PAOD subgroup, subjects with HMGB1 expression had
      higher expression of the autophagy marker LC3A/B and higher mitochondrial DNA
      copy number. HMGB1 may be an inflammatory mediator with roles in oxidative damage
      and proinflammatory and inflammatory processes in diabetic atherogenesis.
      Moreover, it may have dual effects by compensating for increased mitochondrial
      DNA copy number and increased autophagy marker expression. 

PMID- 25966226
TI  - Cumulative methylation alternations of gene promoters and protein markers for
      diagnosis of epithelial ovarian cancer.
AB  - DNA methylation plays an important role in carcinogenesis and cancer development.
      In this study, we examined gene methylation in epithelial ovarian cancer (EOC)
      using cationic conjugated polymer (CCP)-based fluorescence resonance energy
      transfer (FRET) to evaluate the application of cumulative methylation
      alternations of genes associated with cancer antigen 125 for early cancer
      diagnosis. The methylation status of 3 genes (Ras association domain family 1
      isoform A, RASSF1A; opioid-binding protein/cell adhesion molecule, OPCML;
      homeobox A9, HOXA9) were examined and compared in 35 EOC samples and 11 normal
      ovarian tissue samples using CCP-based FRET. Gene methylation levels were
      clustered into 3 sections and assigned a value; values for the 3 genes were
      summed. Although methylation of the OPCML gene was significantly associated with
      stage, histological types, grade, and ascites and that of RASSF1A and HOXA9 was
      not, the sum for the 3 genes was significantly associated with stage and ascites.
      The sum showed higher sensitivity (85.7%) and specificity (100%) for
      discriminating EOC from normal ovarian tissues than did the methylation status of
      RASSF1A, OPCML, and HOXA9 (48.6, 77.1, 77.1, and 100, 88.1, 100%, respectively).
      Combining cancer antigen 125 levels with the sum increased the sensitivity to
      94.3%. The detection and analysis of a panel of genes' methylation status with
      the CCP-based FRET technique may be useful for diagnosis and screening of EOC;
      the associated cancer antigen 125 can be used to increase diagnostic sensitivity.

PMID- 25966227
TI  - Clinicopathological analysis of idiopathic membranous nephropathy in young
      adults.
AB  - The aim of this study was to understand the clinicopathological features and
      prognosis of idiopathic membranous nephropathy (IMN) in youth. A retrospective
      analysis of the clinicopathological features and prognoses of pathologically
      confirmed IMN in 21 patients aged 15-30 years was performed. IMN was mainly
      characterized as nephrotic syndrome (NS), with stage I as the main pathological
      stage, and associated with hyperplasia of the glomerular mesangial cells and
      ground substance. High-intensity immunofluorescence also showed multi-site
      deposition of a variety of immune complexes, and electron microscopy showed multi
      site deposition of electron-condensing substances. In the present study, 4
      patients received non-specific treatment. Among 17 NS patients, 12 patients
      exhibited a preference for glucocorticoid therapy, and of these patients, 7 were
      sensitive to therapy and 5 were resistant. In the 12 patients who received
      hormone treatment combined with immunosuppressants (including 5 patients who were
      treated with the combination from the initial start, 5 patients who were steroid
      resistant, and 2 patients who were sensitive to the initial hormone treatment but
      who later showed relapse), complete remission was achieved in 6 patients, partial
      remission was achieved in 2, the treatment was ineffective in 2, and 2 patients
      were lost to follow-up. In conclusion, the clinical manifestation of IMN in youth
      in this study was mainly NS. In most patients, the initial hormone treatment was
      effective, and in some patients, the combination of hormone and immunosuppressant
      treatment was effective. As the sample size in this study was small, further
      clinical validation is still required to determine the efficacy of the treatment.

PMID- 25966228
TI  - Taxonomic status of Pinus henryi using multiplexed microsatellite markers.
AB  - The taxonomic status of Pinus henryi, a rare species endemic to China, is still
      ambiguous. In this study, the genetic relationships among P. henryi and its
      congeners (P. tabulaeformis, P. tabulaeformis var. mukdensis, and P. massoniana)
      were revealed using multiplexed microsatellite markers, including chloroplast
      microsatellites, nuclear microsatellites, and expressed sequence tag
      microsatellites. The results refute the hypothesis that P. henryi is a subspecies
      of P. tabulaeformis or P. massoniana and support the suggestion that it may be a
      distinct species closely related to P. tabulaeformis.

PMID- 25966229
TI  - Novel bioinformatic identification of differentially expressed tissue-specific
      and cancer-related proteins from the Human Protein Atlas for biomarker discovery.
AB  - Identification of cancer-associated and tissue-specific proteins is important for
      research on carcinogenesis mechanisms and biomarker discovery. Here we performed
      a new strategy to identify candidate cancer proteins by mining
      immunohistochemistry protein profiles. Proteins with quantitative values from 14
      normal tissues and their corresponding cancer tissues were compared and analyzed
      using bioinformatics. The final results included identification of tissue
      specific proteins and differentially expressed proteins in different cancer types
      that are primarily involved in energy metabolism and cell invasion. From the
      tissue-specific proteins, secreted and membrane proteins were further screened
      and functionally clustered. These primarily belonged to the gene families of
      endogenous ligands, cluster of differentiation molecules, and solute carriers,
      and were mainly involved in the processes of cell motility, hormone metabolism,
      adhesion, and trans-port. Further studies are warranted to validate the
      candidates identified herein and substantiate the suggested enriched functions.
      The results from this study might provide a reliable resource to study underlying
      carcinogenesis mechanisms and discover potential cancer targets for the
      development of therapeutic targets and of early diagnosis and disease response
      markers.

PMID- 25966230
TI  - Phylogeographic analysis of African swine fever virus based on the p72 gene
      sequence.
AB  - African swine fever virus (ASFV) outbreak has been considered as an emerging and
      re-emerging disease for almost a century. Diagnostically, simple polymerase chain
      reaction and sequencing-based molecular detection could be employed for both
      viral identification and genotyping. This study established a novel phylogenetic
      analysis and epidemiology comparison based on 205 bp of p72 gene sequences. Based
      on this partial p72 fragment, an updated list of 44 different genotypes from a
      total of 516 ASFV sequences compiled from GenBank was generated. Nucleotide
      diversity was 0.04325 +/- 0.00231. The analysis of spatial genetic variation
      divided the ASFV populations of the African continent into four clades (clade A:
      central and upper eastern Africa; clade B: eastern Africa; clade C: eastern and
      southern Africa; and clade D: southern Africa). These results and the developed
      protocol could serve as useful molecular tools for ASFV diagnosis from degraded
      DNA or putrefied samples, and also provide the phylogeographic perspective to
      identify the origin of viral outbreaks, facilitating the decision planning to
      limit their spread. 

PMID- 25966231
TI  - Molecular cloning and expression analysis of GhLOF genes in upland cotton
      (Gossypium hirsutum L.).
AB  - Shoot branching, i.e., the timing and position of shoot growth, determines to a
      large extend the pattern of plant architecture, and is the result of the
      integration of a plant's genetic background and environmental cues. Many genes
      that are involved in the formation and outgrowth of axillary buds have been
      cloned, but the exact mechanism is still unclear. Branching pattern is an
      important agronomic trait in many crops, including cotton. In the present study,
      we cloned four genes from cotton, and designated them as GhLOF1/2/3/4. Sequence
      analysis revealed that all four genes shared conserved protein domains with
      LATERAL ORGAN FUSION (LOF) from Arabidopsis and TRIFOLIATE (Tf) from tomato.
      Phylogenetic analysis revealed that GhLOF3 and GhLOF4 were close to Tf because of
      their similar expression patterns, whereas GhLOF1 and GhLOF2 were differentially
      expressed.

PMID- 25966232
TI  - Association between the rs189037 single nucleotide polymorphism in the ATM gene
      promoter and cognitive impairment.
AB  - The aim of this study was to explore the existence of a relationship between the
      rs189037 single nucleotide polymorphism (SNP) of the ataxia telangiectasia
      mutated (ATM) gene and cognitive impairment in the elderly (aged 60 years and
      above). In a cohort, 505 residents of Suinung City were consecutively recruited
      and their cognitive function was measured using a 30-point Mini-Mental State
      Examination (MMSE). The subjects were divided into cognitive impairment group and
      control group on the basis of MMSE scores. Presence of the rs189037 SNP variant
      was examined using polymerase chain reaction-restriction fragment length
      polymorphism. The prevalence rates of cognitive impairment were 32.7% in the
      whole sample. The genotype frequencies of the rs189037 polymorphism were 33.5%
      (CC), 50.7% (CT), and 15.8% (TT); the C and T allele frequencies were 58.8 and
      41.2%, respectively. No significant differences in the frequency distributions of
      the CC, CT and TT genotypes were observed between cognitively impaired and
      control groups. We found that the rs189037 SNP was not directly correlated with
      cognitive impairment among the elderly Chinese Han population. 

PMID- 25966233
TI  - Zhi-Long-Huo-Xue-Tong-Yu modulates mitochondrial fission through the ROCK1
      pathway in mitochondrial dysfunction caused by streptozotocin-induced diabetic
      kidney injury.
AB  - Zhi-Long-Huo-Xue-Tong-Yu (ZLHXTY) is a defined mixture of 5 herbs developed by
      Professor S.J. Yang according to the Buyang Huanwu decoction method, which has
      been recorded in the Yilingaicuo. This study investigated the renoprotective
      effects of ZLHXTY on mitochondrial dysfunction induced by diabetic kidney injury
      in a diabetic rat model. Diabetes was induced by a single intravenous injection
      of streptozotocin. Rats were daily fed either ZLHXTY or vehicle beginning in the
      1st week after injection. Levels of mitofusin 2 (mfn2), dynamin-related protein 1
      (Drp1), caspase-9, and rho-associated, coiled-coil-containing protein kinase 1
      (ROCK1) were detected using Western blotting. Levels of intracellular calcium and
      adenosine triphosphate (ATP) were examined using an enzyme-linked immunosorbent
      assay. An electron microscopic examination of kidney tissue was performed. The
      levels of mfn2 and ATP in the diabetes and ZLHXTY groups decreased from the 4th
      week after modeling. The expression levels of Drp1, ROCK1, and caspase-9
      increased in the diabetes group but decreased in the ZLHXTY group from the 4th
      week after modeling. Compared with the diabetes group, ZLHXTY treatment decreased
      the mesangial expansion index and proteinuria levels, and improved the
      pathological changes typical of diabetic kidney injury. Furthermore, ZLHXTY
      treatment inhibited the activation of ROCK1 and expression of Drp1 and caspase-9,
      but did not affect the expression of mfn2. This study indicates that ZLHXTY
      treatment could protect kidney tissue from diabetic injury through the ROCK1
      pathway response to mitochondrial dysfunction induced by diabetes.

PMID- 25966234
TI  - Correlation between polymorphism of platelet alloantigen genes HPA-1-5 and type 2
      diabetes complication by carotid atherosclerosis in a Chinese population.
AB  - We investigated the association between the polymorphism of human platelet
      alloantigen genes HPA-1-HPA-5 and the complication of type 2 diabetes mellitus
      (T2DM) by carotid atherosclerosis (CA) among Han people in Guiyang District,
      China. Ninety-nine T2DM patients were selected from the Affiliated Hospital of
      Guiyang Medical College and divided into a CA(+) group and a CA(-) group. A
      control group comprised 100 healthy people from the medical examination center of
      the same hospital. Genomic DNA from all the subjects was isolated by phenol
      chloroform extraction and target genes were amplified using sequence-specific
      primer-polymerase chain reaction, followed by gene type detection of HPA. There
      were significant differences in allele and genotype frequencies of HPA-1, -2, -3,
      and -5 among the three groups [CA(+), CA(-), and the control group] (P < 0.05),
      and significant differences in allele and genotype frequencies of HPA-1, -2, and 
      3 between groups CA(+) and CA(-) and the control group (P < 0.05). Moreover,
      there was a significant difference in allele and genotype frequencies of HPA-5
      between the CA(+) and CA(-) groups (P < 0.05). Logistic regression analysis
      showed that risk factors for T2DM patients developing a CA complication were age,
      duration of diabetes, high blood pressure, smoking, overweight, abnormal blood
      lipid levels, and polymorphism of HPA-5. There may be a correlation between T2DM
      and polymorphism of HPA-1-3. Polymorphism of HPA- 5 is probably a risk factor for
      CA complicating T2DM. 

PMID- 25966235
TI  - Matrix metalloproteinase variants associated with risk and clinical outcome of
      esophageal cancer.
AB  - We conducted a case-control study to investigate the role of matrix
      metalloproteinase (MMP) 2, MMP3, and MMP9 single nucleotide polymorphisms on
      susceptibility to esophageal squamous cell carcinoma (ESCC) in a Chinese
      population, and their association with environmental factors. A total of 226
      patients with ESCC, and 226 age- and gender-matched healthy controls were
      enrolled in this study. Polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) analysis was carried out on MMP2 -1306 C>T (rs243865),
      MMP3 -1171 5A>6A (rs3025058), and MMP9 -1562 C>T (rs3918242) genotypes.
      Unconditional regression analysis showed that individuals carrying the MMP2 -1306
      TT genotype had a decreased incidence of ESCC compared to those with the CC
      genotype [odds ratio (OR) = 0.32; 95% confidence interval (CI), 0.10-0.89, P
      value = 0.02]. Moreover, MMP9 -1562 CC carriers were associated with an increased
      ESCC risk compared to those with the TT genotype (OR = 2.71; 95%CI, 1.04-7.87, P
      value = 0.02). In the Cox proportional hazards model, after adjusting for
      potential confounding factors, patients carrying the MMP9 -1562 CC genotype had a
      significantly increased risk of death from ESCC (hazard ratio = 2.97; 95%CI, 1.25
      6.87, P value = 0.005). In conclusion, this study showed that the MMP2 -1306 TT
      and MMP9 -1562 CC genotypes were associated with increased ESCC, and patients
      carrying the MMP9 -1562 CC genotype had a significantly increased risk of death
      from ESCC.

PMID- 25966236
TI  - Effects of hydroxycamptothecin on the expression of matrix metalloproteinase-1
      (MMP-1), tissue inhibitor of MMP-1, and type I collagen in rats with pulmonary
      fibrosis.
AB  - The aim of this study was to investigate the effects of hydroxycamptothecin
      (HCPT) on the expression of matrix metalloproteinase-1 (MMP-1), tissue inhibitor
      of MMP-1 (TIMP-1), and type I collagen in the lung tissue of rats with pulmonary
      fibrosis induced by bleomycin A5. We used hematoxylin eosin staining to observe
      the degree of pulmonary fibrosis in rats; Masson staining, reverse transcription
      polymerase chain reaction, and immunohistochemistry were used to observe the
      expression of collagen, MMP-1, and TIMP-1, and type I collagen. The expression of
      MMP-1 in the model group decreased significantly, while the expression of TIMP-1
      and type I collagen significantly increased. After treatment with HCPT, the
      degree of pulmonary fibrosis and the expression of TIMP-1 and type I collagen
      decreased in all treatment groups. However, the expression of MMP-1 increased in
      a dose-dependent manner. Our results showed that HCPT decreased the pulmonary
      fibrosis induced by bleomycin A5 in rats, and an increase in MMP-1 expression and
      decrease in the TIMP-1 and type I collagen expression may be the mechanism that
      regulates the metabolism of the extracellular matrix. 

PMID- 25966237
TI  - Development and characterization of microsatellite loci in Megalonibea fusca.
AB  - Megalonibea fusca is a commercially important large edible fish. In this study,
      the first set of 10 polymorphic microsatellite loci for M. fusca was developed
      and characterized. The number of alleles per locus ranged from two to five, with
      the observed and expected heterozygosities ranging from 0.0667 to 0.7667, and
      from 0.0644 to 0.5828, respectively. Most of the loci were in Hardy-Weinberg
      equilibrium (P > 0.05), except for two loci (Mf25 and Mf30) after a Bonferroni's
      correction (P < 0.005). These informative microsatellite markers will be useful
      in further studies of the population and conservation genetics of this species. 

PMID- 25966238
TI  - Application of molecular markers to detect DNA damage caused by environmental
      pollutants in lichen species.
AB  - Pseudevernia furfuracea L. (Zopf), Peltigera praetextata (Florke ex Sommerf.)
      Zopf, Lobaria pulmonaria (L.) Hoffm., and Usnea longissima Ach. lichen species
      were used as bioindicators to assess the genotoxicity of air pollutants. In the
      present study, we examined significant environmetal pollutants and investigate
      how changes may lead to damage in DNA structure using RAPD markers. In the study
      area (Erzurum, Turkey), poor-quality lignite, which generates a large amount of
      sulfur dioxide, nitrogen oxides, and particle matter, is used for domestic
      heating, and vehicles also contribute to air pollution. Control lichen samples
      were collected far from large urban and industrial settlements and transplanted
      to four polluted sites for 4, 8, or 12 months. The total soluble protein content
      of the examined four lichen species did not significantly change with exposure
      time (P < 0.05). The four lichen samples exposed to the pollutants for 8 months
      had the highest ratio of DNA changes. The ratio of band differences in P.
      praetextata was higher than that in the other three lichen species, possibly
      because it has broad leaves that accumulated more pollutants. The average
      incidences of polymorphism were 64.14, 54.58, 65.76, and 43.06% for P.
      furfuracea, P. praetextata, L. pulmonaria, and U. longissima, respectively. The
      genomic template stability (GTS) significantly decreased following exposure to
      pollutants. GTS ratios revealed that the highest value (98.36%) belonged to U.
      longissima samples from Site 1 (10 m) after 4 months of exposure, and the lowest
      values belonged to P. praetextata (73.58%) from Site 3 (100 m) after 8 months of
      exposure. Based on our findings, we recommend the use of P. praetextata as an
      indicator of genotoxicity.

PMID- 25966239
TI  - Efficacy of combined hepatitis B immunoglobulin and hepatitis B vaccine in
      blocking father-infant transmission of hepatitis B viral infection.
AB  - The aim of this study was to examine the efficacy of combined immunization of
      hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine (HBVac) in blocking
      father-infant transmission of hepatitis B virus (HBV). Newborns positive at birth
      for blood HBV sur-face antigen (HBsAg) and/or HBV DNA were selected and immunized
      with HBIG combination HBVac. At 7 months, HBV markers and HBV DNA of each neonate
      were measured using electrochemiluminescence with the Cobas-e-411 Automatic
      Electrochemiluminescence Immuno-assay Analyzer and fluorescence quantitative
      polymerase chain reaction. Among all 7-month-old subjects, the negative
      conversion rates of HBV DNA and HBsAg were 48/61 (78.7%) and 19/41 (46.3%),
      respectively. Therefore, this study demonstrated that prompt combination
      injection of HBIG and HBVac can protect some of the HBV DNA- and/ or HBsAg
      positive newborns from HBV.

PMID- 25966240
TI  - Detection of Toxoplasma gondii DNA in Brazilian oysters (Crassostrea
      rhizophorae).
AB  - The aim of this study was to detect evidence of Toxoplasma gondii using
      polymerase chain reaction (PCR)-based techniques in oysters (Crassostrea
      rhizophorae) obtained from the southern coastal region of Bahia, Brazil. A total
      of 624 oysters were collected, and the gills and digestive glands were dissected.
      Each tissue sample was separated into pools containing tissues (of the same type)
      from three animals, leading to a total of 416 experimental samples for analysis
      (208 samples each from the gills and digestive glands). Molecular analysis using
      PCR-based detection of the T. gondii AF 146527 repetitive fragment yielded
      negative results for all samples. However, when nested-PCR was used for detection
      of the T. gondii SAG-1 gene, 17 samples were positive, with the gills being the
      tissue with maximal detection of the parasite. These positive results were
      confirmed by sample sequencing. It is therefore suggested that C. rhizophorae
      oysters are capable of filtering and retaining T. gondii oocysts in their tissue.
      This represents a risk to public health because they are traditionally ingested
      in natura. 

PMID- 25966241
TI  - Molecular cloning and expression analysis of MyD88 in spiny head croaker,
      Collichthys lucidus.
AB  - Myeloid differentiation factor 88 (MyD88) is an important adaptor protein
      involved in toll-like receptor signaling pathways. In this study, a cDNA library
      from Collichthys lucidus was constructed using the SMART technique. A complete
      cDNA sequence showing high identity with the conserved sequence of the MyD88 gene
      was cloned from the cDNA library using expressed sequence tag analysis and rapid
      amplification of cDNA ends, and then subjected to further investigation. The full
      length cDNA of MyD88 from C. lucidus (ClMyD88) was 1580 bp, including a 5'
      terminal untranslated region (UTR) of 102 bp, a 3'-terminal UTR of 614 bp, and an
      open reading frame of 864 bp. The gene encoded a polypeptide of 287 amino acids,
      constituting a predicted molecular weight of 33.03 kDa and a theoretical
      isoelectric point of 5.06. It contained a typical death domain at the N-terminal
      and a conservative toll/IL-1 receptor domain structure at the C-terminal.
      Quantitative real-time reverse transcription PCR analysis revealed broad
      expression of ClMyD88, with the highest expression in the gill and the weakest
      expression in the brain and muscle. These results indicated that MyD88 has an
      important role in the innate immune system in C. lucidus. 

PMID- 25966242
TI  - A rapid and sensitive loop-mediated isothermal amplification procedure (LAMP) for
      Mycoplasma hyopneumoniae detection based on the p36 gene.
AB  - The aim of this study was to establish a method for sensitive and rapid diagnosis
      of Mycoplasma hyopneumoniae in clinical specimens. To this effect, we employed
      three sets of primers specifically designed for amplification of nucleic acids
      under isothermal conditions. After optimization of reaction conditions, M.
      hyopneumoniae could be successfully detected at 63 degrees C in 45 min through
      use of the loop-mediated isothermal amplification (LAMP) assay. A positive
      reaction was identified visually as white precipitate and confirmed by gel
      electrophoresis. The detection limit for this assay was 10 copies/MUL, as
      observed by electrophoretic analysis. The accuracy of the LAMP reaction was
      confirmed by restriction endonuclease digestion as well as by direct sequencing
      of the amplified product. This method can specifically detect M. hyopneumoniae;
      other species with high homology and other bacterial and virus strains gave
      negative results. To test the utility of this procedure, the LAMP assay was
      applied to 40 clinical samples collected from swine lung tissues experimentally
      challenged with M. hyopneumoniae isolates, and compared to the results from a
      real-time polymerase chain reaction (PCR) assay. A concordance of 100% was
      observed between the two assays. In conclusion, the results from our study
      demonstrated that the LAMP assay provided a rapid reaction and was inexpensive to
      perform, with no need of complex instruments or systems such as Geneamp PCR. The
      LAMP assay may therefore be applied in routine diagnosis in the clinical
      laboratory and for in-field detection of M. hyopneumoniae infection. 

PMID- 25966243
TI  - Selection of putative Terra Maranhao plantain cultivar mutants obtained by gamma
      radiation.
AB  - The aim of this study was to select putative Terra Maranhao plantain cultivar
      mutants obtained by gamma radiation, with good agronomic traits and short height.
      A total of 315 buds were irradiated in vitro with gamma rays in doses of 20 Gy
      and were subcultivated and evaluated in the field over 2 production cycles. The
      clones were evaluated to select the best 10% of the plants. Cultivation was
      undertaken at a spacing of 3 x 4 m, and fertilization was carried out according
      to the technical recommendations for the crop. A total of 111 irradiated plants
      and 41 controls were evaluated in the field. Among the irradiated plants
      selected, genotypes that exhibited reduced height were observed. The genotypes
      Irra 04, Irra 13, Irra 19, and Irra 21 exhibited a height of 3.6 m, which was
      below the mean value of the controls selected. Other irradiated genotypes
      selected such as Irra 14 and Irra 16, with a height of 3.65 m, are promising
      because, in addition to reduced height, they exhibited good bunch weight and
      shorter period to flowering in relation to the mean value of the controls, which
      is a significant factor for the next stages in breeding. These results confirm
      the possibility of inducing mutations in Terra type banana plants to obtain
      desirable agronomic traits and short height.

PMID- 25966244
TI  - Isolation and characterization of microsatellite markers for Axonopus compressus
      (Sw.) Beauv. (Poaceae) using 454 sequencing technology.
AB  - Axonopus compressus (Sw.) Beauv. is a perennial herb widely used as a garden lawn
      grass. In this study, we used Roche 454 pyrosequencing, combined with the
      magnetic bead enrichment method FIASCO, to isolate simple sequence repeat markers
      from the A. compressus genome. A total of 1942 microsatellite loci were
      identified, with 53,193 raw sequencing reads. One hundred micro-satellite loci
      were selected to test the primer amplification efficiency in 24 individuals; 14
      primer pairs yielded polymorphic amplification products. The number of observed
      alleles ranged from two to six, with an average of 3.5. Shannon's Information
      index values ranged from 0.169 to 0.650, with an average of 0.393. Nei's genetic
      diversity values ranged from 0.108 to 0.457, with an average of 0.271. This first
      set of microsatellite markers developed for Axonopus will assist in the
      development of molecular marker-assisted breeding and the assessment of genetic
      diversity in A. compressus.

PMID- 25966245
TI  - Expression of genes associated with the biosynthetic pathways of abscisic acid,
      gibberellin, and ethylene during the germination of lettuce seeds.
AB  - Seed germination and dormancy are complex phenomena that are controlled by many
      genes and environmental factors. Such genes are indicated by phytohormones that
      interact with each other, and may cause dormancy or promote seed germination. The
      objective of this study was to investigate gene expression associated with the
      biosynthetic pathways of abscisic acid (ABA), gibberellic acid (GA), and ethylene
      (ET) in dormant and germinated lettuce seeds. The expressions of LsNCED,
      LsGA3ox1, and ACO-B were evaluated in germinating and dormant seeds from the
      cultivars Everglades, Baba de Verao, Veronica, Salinas, Colorado, and Regina 71.
      The expressions of LsNCED, LsGA3ox1, and ACO-B were related to the biosynthesis
      of ABA, GA, and ET, respectively; therefore, the presence of these substances
      depends on genotype. LsNCED expression only occurred in dormant seeds, and was
      connected to dormancy. LsGA3ox1expression only occurred in germinated seeds, and
      was connected to germination. The ACO-B gene was involved in ET biosynthesis, and
      was expressed differently in germinated and dormant seeds, depending on the
      genotype, indicating different functions for different characteristics.
      Furthermore, sensitivity to phytohormones appeared to be more important than the
      expression levels of LsNCED, LsGA3ox1, or ACO-B.

PMID- 25966246
TI  - Values for serum procalcitonin, C-reactive protein, and soluble triggering
      receptor expressed on myeloid cells-1 in predicting survival of patients with
      early-onset stroke-associated pneumonia.
AB  - We examined the value of serum procalcitonin (PCT), C-reactive protein (CRP),
      soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) for predicting
      the survival of patients with early-onset stroke associated pneumonia (EOP). A
      total of 207 stroke patients were enrolled, and 91 developed EOP. Upon admission,
      serum PCT, CRP, sTREM-1 levels, clinical pulmonary infection score, and Acute
      Physiology and Chronic Health Evaluation II score were all significantly higher
      in patients with EOP than in those without EOP (P < 0.05). Of the 91 patients who
      developed EOP, 39 (42.9%) died (non-survivors) within 28 days. The Acute
      Physiology and Chronic Health Evaluation II score on admission was significantly
      higher in non-survivors than in survivors (P < 0.05). Serum PCT and sTREM-1
      levels were slightly elevated on days 1, 3, and 5 in non-survivors and gradually
      decreased in survivors. Serum PCT, sTREM-1, and CRP levels were all significantly
      higher in non-survivors than in survivors on days 1, 3, and 5 (P < 0.05). The
      sensitivity and specificity of PCT for predicting the outcome of EOP were 84.6
      and 71.2%, the sensitivity and specificity of sTREM-1 were 71.8 and 92.3%, and
      the sensitivity and specificity of sTREM-1 combined with PCT were 74.4 and 96.2%.
      Serum PCT combined with sTREM-1 accurately predicted the outcome of EOP patients,
      and dynamic monitoring of serum PCT and sTREM-1 levels is necessary.

PMID- 25966247
TI  - Identification of differentially expressed genes associated with flower color in
      peach using genome-wide transcriptional analysis.
AB  - Flower color is an important trait of the ornamental peach (Prunus persica L.).
      However, the mechanism responsible for the different colors that appear in the
      same genotype remains unclear. In this study, red samples showed higher
      anthocyanins content (0.122 +/- 0.009 mg/g), which was significantly different
      from that in white samples (0.066 +/- 0.010 mg/g). Similarly to carotenoids
      content, red extract (0.058 +/- 0.004 mg/L) was significantly higher in white
      extract (0.015 +/- 0.004 mg/L). We estimated gene expression using Illumina
      sequencing technology in libraries from white and red flower buds. A total of
      3,599,960 and 3,464,141 tags were sequenced from the 2 libraries, respectively.
      Moreover, we identified 106 significantly differentially expressed genes between
      the 2 libraries. Among these, 78 and 28 represented transcripts with a higher or
      lower abundance of more than 2-fold than in the white flower library,
      respectively. GO annotation indicated that highly ranked genes were involved in
      the pigment biosynthetic process. Expression patterns of 11 genes were verified
      using quantitative reverse transcription-polymerase chain reaction assays. The
      results suggest that hydroxycinnamoyl-coenzyme A shikimate/quinate
      hydroxycinnamoyltransferase, 2-oxoglutarate-dependent dioxygenase, isoflavone
      reductase, riboflavin kinase, zeta-carotene desaturase, and ATP binding cassette
      transporter may be associated with the flower color formation. Our results may be
      useful for scientists focusing on Prunus persica floral development and
      biotechnology. 

PMID- 25966248
TI  - Effects of propofol and etomidate pretreatment on glucocorticoid receptor
      expression following induction of sepsis in rats.
AB  - The aim of this study was to determine the effect of etomidate and propofol
      pretreatment on the expression of glucocorticoid receptor and the prognosis of
      sepsis. The sepsis rat was used as a model. During glucocorticoid treatment,
      etomidate and propofol were applied alone or together at different time points.
      Survival curves, glucocorticoid receptor expression in the rat adrenal cortex,
      and inflammation levels were determined. The outcome of sepsis in rats was
      evaluated based on the combined utilization of propofol and etomidate. The
      results indicated that the combined utilization of propofol and etomidate
      pretreatment could significantly improve the effects of glucocorticoids on rat
      sepsis. Etomidate was shown to enhance the expression of the glucocorticoid
      receptor, while propofol was shown to inhibit the inflammatory response.
      Etomidate was best used immediately after modeling, whereas propofol was most
      suitable for use during the peak inflammatory reaction. These results
      demonstrated that anesthetics had the ability to enhance the effect of
      glucocorticoids in the treatment of sepsis. Etomidate was indicated for use in
      the early stage of inflammation to enhance expression of the glucocorticoid
      receptor, while propofol application was indicated at the peak of the
      inflammatory reaction owing to its strong anti-inflammation effect. 

PMID- 25966249
TI  - Characterization of abnormal epithelium after laser-assisted subepithelial
      keratectomy using in vivo confocal microscopy.
AB  - This study compared the abnormal corneal epithelium after laser-assisted
      subepithelial keratectomy (LASEK) with dystrophic cornea using in vivo using
      confocal microscopy (IVCM) and examined the effects of the abnormal epithelium on
      postoperative recovery of uncorrected distance visual acuity (UDVA) and sub-basal
      nerve plexus regeneration. The UDVA and wound healing were examined in 50 eyes of
      25 patients undergoing LASEK at 1 week, 1 month, and 1 year postoperatively,
      including the visual acuity, slit lamp microscopy, and IVCM. After 1 week, the
      corneal epithelium was healed in all patients, but abnormal epithelial cells were
      detected in 33/50 patients using IVCM. Abnormal cells were limited to the
      surgical margin, and highly reflective granules were observed underneath. At 1
      month and 1 year postoperatively, the abnormal epithelium was unchanged in size.
      At 1 year postoperatively, there were clear differences between the sub-basal
      nerve plexus in the normal and abnormal epithelium. At 1 month postoperatively,
      the UDVA was >1.0 in 88% of patients, which increased to 94% at 1 year, and there
      was no clear difference in the UDVA between abnormal (N = 33) and normal (N = 17)
      epithelium. After LASEK, abnormal epithelial cells may arise at the margin of the
      epithelial flap and persist 1 year postoperatively accompanied by poor
      regeneration of the sub-basal nerve plexus. However, this does not affect the
      UDVA postoperatively. The abnormal epithelium may be caused by residual necrotic
      basal cell debris on the epithelial basement membrane and abnormal neurotrophic
      metabolism between the corneal epithelium and nerve plexus.

PMID- 25966250
TI  - Identification of novel compound heterozygous RECQL4 mutations and prenatal
      diagnosis of Baller-Gerold syndrome: a case report.
AB  - Birth defects are structural and/or functional malformations present at birth
      that cause physical or mental disability and are important public health
      problems. Our study was aimed at genetic analysis and prenatal diagnosis of
      congenital anomalies to understand the cause of certain birth defects. Karyotypes
      and array-comparative genomic hybridization (aCGH) were performed on a pregnant
      woman, surrounding amniotic fluid, and her husband. A short-stature panel genetic
      test was conducted in accordance with the phenotype of the fetus. Following
      examination, it was determined that the karyotype and aCGH results were normal.
      The RECQL4 gene in the fetus showed compound heterozygous mutations, and each
      parent was found to be a carrier of one of the mutations. The two heterozygous
      mutations (c.2059-1G>C and c.2141_2142delAG) were detected in the RECQL4
      (NM_004260) gene in the fetus; therefore, the fetus was predicted to have Baller
      Gerold syndrome. These two mutations have not previously been reported. In
      addition, these results identified a 25% risk of the parents having a sec-ond
      conceptus with this congenital disease. Therefore, prenatal genetic diagnosis was
      highly recommended for future pregnancies.

PMID- 25966251
TI  - Functional polymorphisms in microRNA gene and hepatitis B risk among Asian
      population: a meta-analysis.
AB  - Genetic mutations in microRNA gene can alter expression, which may interact to
      increase the risk of developing various diseases, including hepatitis B. However,
      published results are inconclusive or ambiguous. The aim of this review and meta
      analysis is to more precisely estimate the association between polymorphisms in
      microRNA genes and hepatitis B risk. A digital search was performed of the
      MEDLINE EMBASE, CNKI, and CBM databases to identify relevant articles published
      up to February 18, 2014. Ten case-control studies were included, with a total of
      6042 patients with hepatitis B and 6834 healthy controls. Nine single-nucleotide
      polymorphisms in the miRNA gene were examined, including miR-34b/c [rs4938723
      (T>C)], miR-196a-2 [rs11614913 (C>T)], miR-146a [rs2910164 (G>C)], miR-499
      [rs3746444 (T>C)], miR-122 [rs3783553 (ins/del)], miR-149 [rs2292832 (C>T)], miR
      106b-25 [rs999885 (A>G)], miR-let-7c [rs6147150 (ins/del)], and miR-218
      [rs11134527 (A>G)]. The meta-analysis results indicated that the miR-196a-2*T,
      miR-122*del, miR-106b-25*A, and miR-let-7c*del alleles/carriers increase the risk
      of hepatitis B among the Asian population. However, the miR-146a, miR- 499, miR
      149, miR-218, and miR-34b/c polymorphisms may not be linked with the risk of
      hepatitis B. Further investigations are warranted to determine the exact
      associations between microRNA mutations and hepatitis B susceptibility.

PMID- 25966252
TI  - Effects of analgesia methods on serum IL-6 and IL-10 levels after cesarean
      delivery.
AB  - This study aimed to discuss the effects of 3 different analgesia methods on serum
      IL-6 and IL-10 in patients after cesarean delivery. Thirty full-term women, who
      underwent cesarean delivery, were randomly assigned to 3 analgesia groups (10
      cases each) as follows: intramuscular injection of 100 mg pethidine (NC group),
      patient controlled epidural analgesia (PCEA) of 5 mg morphine plus 150 mg
      ropivacaine (MR group), and patient controlled intravenous analgesia (PCIA) of
      150 mg sufentanil plus 5 mg droperidol (SF group). An electronic analgesia pump
      was available in all 3 groups. At 4, 12, 24, and 48 h after surgery, visual
      analogue scale (VAS) pain scores were evaluated, IL-6 and IL-10 serum levels were
      measured, and adverse reactions were documented. The MR and SF groups responded
      well to analgesia. VAS scores at 12 and 24 h in these 2 groups were significantly
      lower than those in the NC group (P < 0.05). IL-6 and IL-10 levels were elevated
      to varying degrees postoperatively in all 3 groups. In the MR and SF groups, no
      significant difference occurred at each time point (P > 0.05), but compared with
      the NC group, significant differences were observed at 12 and 24 h (P < 0.05).
      Both PCIA and PCEA produced good analgesic effect, decreased postoperative level
      of serum IL-6, promoted release of anti-inflammatory factor IL-10, maintained
      balance in postoperative serum IL-6 level, and reduced the postoperative
      inflammatory response. Adverse reactions were significantly higher with epidural
      morphine than with intravenous sufentanil. 

PMID- 25966253
TI  - Transcriptome analysis of Arabidopsis seedlings responses to high concentrations
      of glucose.
AB  - Sugars acting as fuel energy or as signaling molecules play important roles in
      plant growth and development. Although sugars associated with early seedling
      development have been analyzed in detail, few studies have examined the effect of
      sugar on genome-wide gene transcription. To analyze the role of glucose on the
      genomic level, we examined the response of seedlings to 5% glucose using RNA-seq
      technology. High concentrations of glucose significately altered the expression
      of 863 genes, with 558 upregulated and 305 downregulated genes by more than 2
      fold. A large number of genes affected by glucose were involved in metabolic
      processes and signaling. Transcript levels for many kinases and calcium signals
      were downregulated. Most transcription factors identified were also involved in
      glucose signaling. Moreover, many genes related to the auxin, gibberellin, and
      abscisic acid responses were upregulated or downregulated. Additionally, the
      K(+), Ca(2+), SO3(-), NO3(-), PO4(3-), amino acid, and sugar transporters were
      also upregulated or downregulated. These results provide a basic understanding of
      the glucose-mediated molecular mechanisms in the regulation of early seedling
      development. 

PMID- 25966254
TI  - Bioinformatic analysis of the effect of type II diabetes on skin wound healing.
AB  - We examined the relationship between type 2 diabetes and skin wound healing.
      GSE38396 was downloaded from the Gene Expression Omnibus database and
      preprocessed using the RMA function of the Affy package. Differentially expressed
      genes (DEGs) were identified using the limma package, then DAVID was applied to
      per-form Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and
      Genomes pathway enrichment analysis. MicroRNAs and their target genes were
      screened from the miRecords database and subjected to functional analysis.
      Finally, the STRING online database was applied to identify the protein-protein
      interaction relationships, and a combined score > 0.5 was considered to indicate
      an interaction. A total of 421 DEGs (208 upregulated and 213 downregulated genes)
      were identified in the skin lymphatic endothelial cells of patients with type II
      diabetes. Twenty-four microRNAs and 34 target genes were screened, including
      those involved in cell migration, regulation of cell proliferation, cell death,
      and cell adhesion regulation, among others. Protein-protein interaction network
      clustering analysis identified a module composed of 25 genes, and INTERPRO
      protein domain enrichment analysis showed that the protein domain of the
      clustering module main-ly contained the insulin-like growth factor binding
      proteins IGFBP3 and CYR61. IGFBP3 and CYR61 may play important roles in skin
      wound healing in diabetes patients. This information may be useful for developing
      methods to treat skin refractory wounds in type II diabetes.

PMID- 25966255
TI  - Next-generation sequencing identification and characterization of microsatellite
      markers in Aconitum austrokoreense Koidz., an endemic and endangered medicinal
      plant of Korea.
AB  - We used next-generation sequencing to develop 9 novel microsatellite markers in
      Aconitum austrokoreense, an endemic and endangered medicinal plant in Korea.
      Owing to its very limited distribution, over-harvesting for traditional medicinal
      purposes, and habitat loss, the natural populations are dramatically declining in
      Korea. All novel microsatellite markers were successfully genotyped using 64
      samples from two populations (Mt. Choejeong, Gyeongsangbuk-do and Ungseokbong,
      Gyeongsangnam-do) of Gyeongsang Province. The number of alleles ranged from 2 to
      7 per locus in each population. Observed and expected heterozygosities ranged
      from 0.031 to 0.938 and from 0.031 to 0.697, respectively. The novel markers will
      be valuable tools for assessing the genetic diversity of A. austrokoreense and
      for germplasm conservation of this endangered species. 

PMID- 25966256
TI  - Identification of highly expressed host microRNAs that respond to white spot
      syndrome virus infection in the Pacific white shrimp Litopenaeus vannamei
      (Penaeidae).
AB  - MicroRNAs (miRNAs) are known to play an important role in regulating both
      adaptive and innate immunity. Pacific white shrimp (Litopenaeus vannamei) is the
      most widely farmed crustacean species in the world. However, little is known
      about the role miRNAs play in shrimp immunity. To understand the impact of viral
      infection on miRNA expression in shrimp, we used high-throughput sequencing
      technology to sequence two small RNA libraries prepared from L. vannamei under
      normal and white spot syndrome virus (WSSV) challenged conditions. Approximately
      19,312,189 and 39,763,551 raw reads corresponding to 17,414,787 and 28,633,379
      high-quality mappable reads were obtained from the two libraries, respectively.
      Twelve conserved miRNAs and one novel miRNA that were highly expressed (>100 RPM)
      in L. vannamei were identified. Of the identified miRNAs, 8 were differentially
      expressed in response to the virus infection, of which 1 was upregulated and 7
      were downregulated. The prediction of miRNA targets showed that the target genes
      of the differentially expressed miRNAs were related to immunity, apoptosis, and
      development functions. Our study provides the first characterization of L.
      vannamei miRNAs in response to WSSV infection, which will help to reveal the
      roles of miRNAs in the antiviral mechanisms of shrimp. 

PMID- 25966257
TI  - Genetic divergence for high-molecular weight glutenin subunits (HMW-GS) in
      indigenous landraces and commercial cultivars of bread wheat of Pakistan.
AB  - Wheat flour quality is an important consideration in the breeding and development
      of new cultivars. A strong association between high-molecular weight glutenin
      subunits (HMW-GS) and bread making quality has resulted in the widespread
      utilization of HMW-GS in wheat breeding. In this study, we analyzed 242 lines of
      wheat, including landraces from the provinces of Punjab and Baluchistan, as well
      as the commercial varieties of Pakistan, to determine allelic variation in the
      Glu-A1, Glu-B1, and Glu-D1 loci encoding HMW-GS. Higher genetic diversity was
      observed for HMW-GS in landraces from Baluchistan, followed by landraces
      collected from Punjab and then commercial varieties. Rare and uncommon subunits
      were observed in Glu-B1, whereas Glu-A1 was less polymorphic. However, Glu-B1 was
      the highest contributor to overall diversity (78%), with a total of 31 rare
      alleles, followed by Glu-D1 (20%) with the high quality 5+10 allele and other
      variants. Commercial cultivars possessed favorable alleles, potentially from
      indirect selection for wheat flour quality by the breeders; however, this
      indirect selection has decreased the pedigree base of commercial cultivars. The
      allelic combinations, including 2*, 5+10, and 17+18, showing high quality scores
      were frequent among landraces, indicating their usefulness in future crop
      improvement and breeding programs. 

PMID- 25966259
TI  - Role of a liver fatty acid-binding protein gene in lipid metabolism in chicken
      hepatocytes.
AB  - This study investigated the role of the chicken liver fatty acid-binding protein
      (L-FABP) gene in lipid metabolism in hepatocytes, and the regulatory
      relationships between L-FABP and genes related to lipid metabolism. The short
      hairpin RNA (shRNA) interference vector with L-FABP and an eukaryotic expression
      vector were used. Chicken hepatocytes were subjected to shRNA-mediated knockdown
      or L-FABP cDNA overexpression. Expression levels of lipid metabolism-related
      genes and biochemical parameters were detected 24, 36, 48, 60, and 72 h after
      transfection with the interference or overexpression plasmids for L-FABP,
      PPARalpha and L-BABP expression levels, and the total amount of cholesterol, were
      significantly affected by L-FABP expression. L-FABP may affect lipid metabolism
      by regulating PPARalpha and L-BABP in chicken hepatocytes. 

PMID- 25966258
TI  - Relationship between carotid artery atherosclerosis and sulfatide in hypertensive
      patients.
AB  - Hypertension is a major traditional risk factor for atherosclerosis, and carotid
      artery intima-media thickness (IMT) is considered to be an important marker of
      atherosclerosis. Sulfatides have been shown to play a role in atherogenesis and
      vascular inflammation, resulting in atherosclerosis. This study aimed to assess
      the association between serum sulfatide and carotid artery IMT among hypertensive
      patients. We chose 60 hypertensive patients and 30 matched healthy controls. All
      subjects had medical examinations at Hebei General Hospital between March 2011
      and March 2012. Measurements and other factors compared included serum sulfatide
      level, carotid artery IMT, and conventional cardiovascular risk factors.
      Hypertensive patients had higher BMIs (24.4 +/- 7.6 to 23.1 +/- 3.1 kg/m(2)),
      total cholesterol levels (5.5 +/- 0.6 to 5.0 +/- 1.1 mM), serum sulfatide levels
      (3.5 +/- 3.9 to 8.3 +/- 2.7 MUM), and carotid artery IMTs (1.06 +/- 0.15 to 0.79
      +/- 0.07 mm) (all P < 0.05) than control patients. Furthermore, the serum
      sulfatide level positively correlated with carotid IMT in the hypertensive
      patients (r = 0.39, P = 0.002). Multiple linear regression analysis showed serum
      sulfatide was an independent risk factor affecting IMT (P = 0.04). These results
      suggest that serum sulfatide is more strongly associated with carotid artery IMT
      than other traditional risk factors in hypertensive patients. 

PMID- 25966260
TI  - Computed tomography-guided percutaneous microwave ablation therapy for lung
      cancer.
AB  - This study evaluated the clinical efficacy and value of computed tomography (CT)
      guided percutaneous microwave ablation therapy (PMAT) for lung cancer without
      surgical treatment. A total of 39 lesions in 29 patients with peripheral lung
      cancer were treated by CT-guided PMAT under local anesthesia. The microwave
      energy was 50-70 W at a frequency of 2450 MHz. The treatment was performed by
      using 1 or 2 points of ablation emission according to the size and shape of the
      tumor. Operations were completed in 29 patients. The average operating time was 8
      min (range: 5-12 min). After PMAT, lower density in the ablated area was observed
      by CT. Pre- and post-treatment CT values were 52.60 and 26.12 Hu, respectively.
      Eight, 14, 4, and 3 patients achieved complete remission, partial remission,
      stable status, and progression, respectively, for an effectiveness rate of
      75.86%. Complications included 5, 2, and 15 cases of pneumothorax, pleural
      effusion, and fever, respectively. No needle track implantation was observed.
      Mean progression-free survival was 14.6 months. The 1- and 2-year survival rates
      were 91.3 and 82.6%, respectively. Thus, PMAT is a minimally invasive, safe, and
      effective treatment for lung cancer. It can improve quality of life, prolong
      survival, and improve the survival rate. 

PMID- 25966261
TI  - Genetic diversity and historical demography of the narrow-range endemic Alpine
      toad, Scutiger liupanensis, in the Liupan Mountains of central China.
AB  - The genetic diversity and historical demography of the narrow-range endemic
      Alpine toad, Scutiger liupanensis, in the Liupanshan National Forest Park of
      central China were estimated using cytochrome b and cytochrome c oxidase subunit
      I (COI) from 85 individuals from five local populations. Both the haplotype
      diversity (Hd) and the nucleotide diversity (Pi) were very high. Phylogenetic
      analysis of the 63 haplotypes revealed two major clades, and an analysis of
      molecular variance attributed most of the variation to within populations. Mantel
      tests did not reveal an isolation by distance pattern of genetic divergence
      between populations, and SAMOVA showed no phylogeographic structure. The results
      of neutrality tests, mismatch distribution analyses, and allelic frequency
      spectra suggest that a sudden demographic expansion occurred, and that high
      genetic variation is beneficial to the survival and development of this species. 

PMID- 25966262
TI  - Ascorbate peroxidase from Jatropha curcas enhances salt tolerance in transgenic
      Arabidopsis.
AB  - Ascorbate peroxidase (APX) plays a central role in the ascorbate-glutathione
      cycle and is a key enzyme in cellular H2O2 me-tabolism. It includes a family of
      isoenzymes with different character-istics, which are identified in many higher
      plants. In the present study, we isolated the APX gene from Jatropha curcas L,
      which is similar with other previously characterized APXs as revealed by
      alignment and phylogenetic analysis of its deduced amino acid sequence. Real-time
      qPCR analysis showed that the expression level of JcAPX transcript significantly
      increased under NaCl stress. Subsequently, to elucidate the contribution of JcAPX
      to the protection against salt-induced oxi-dative stress, the expression
      construct p35S: JcAPX was created and transformed into Arabidopsis and
      transcribed. Under 150-mM NaCl stress, compared with wild type (WT), the
      overexpression of JcAPX in Arabidopsis increased the germination rate, the number
      of leaves, and the rosette area. In addition, the transgenic plants had longer
      roots, higher total chlorophyll content, higher total APX activity, and lower
      H2O2 content than the WT under NaCl stress conditions. These results suggested
      that higher APX activity in transgenic lines increases the salt tolerance by
      enhancing scavenging capacity for reactive oxygen spe-cies under NaCl stress
      conditions. 

PMID- 25966263
TI  - Polymorphisms of the Osteocrin gene and its association with meat quality traits
      in Qinchuan cattle.
AB  - Here, we detected 2 SNPs, A85C and T335C, that were located on the 3rd exon and
      the 3 untranslated regions of the bovine Osteocrin gene, respectively, using 413
      Qinchuan cattle DNA samples. PCR-SSCP and DNA sequencing methods were
      specifically used. Three genotypes (AA, AC, and CC) were found at A85C; yet, only
      2 genotypes (TC and CC) were found at T335C. Association analysis showed that
      both loci were associated with certain meat quality traits, including back fat
      thickness and loin muscle area. At the A85C locus, individuals with the CC
      genotype had greater back fat thickness. In comparison, at the T335C locus,
      individuals with the TC genotype had greater back fat thickness and a larger loin
      muscle area. Therefore, these 2 SNPs could be used as genetic markers to enhance
      Qinchuan cattle breeding programs. 

PMID- 25966264
TI  - Comparison of integrated traditional Chinese and western medicine therapy on
      vascular cognitive impairment with no dementia.
AB  - The aim of this study was to investigate the clinical effect of western medicine
      therapy assisted by Ginkgo biloba tablets (GBT) in patients with vascular
      cognitive impairment with no dementia (VCIND). Eighty patients with VCIND were
      randomly divided into two groups: the conventional treatment group (control
      group) and the combined treatment group. The conventional treatment group was
      provided with anti-platelet aggregation conventional treatment. In this group, 75
      mg aspirin was given three times a day for 3 months, whereas the combined
      treatment group was given 19.2 mg GBT three times a day for 3 months along with
      conventional anti-platelet aggregation treatment. Montreal cognitive assessment
      (MoCA) and transcranial Doppler ultrasonography were used to observe changes in
      cognitive ability and cerebral blood flow in patients with VCIND before and after
      treatment in the two groups. After 3 months of treatment, the MoCA scores of
      execution, attention, abstraction, delayed memory, and orientation were
      significantly increased in the combined treatment group compared with those
      before treatment and those in the control group after treatment. In addition, the
      blood flow velocity of the anterior cerebral artery was significantly increased
      in the combined treatment group. GBT can improve the therapeutic efficacy,
      cognitive ability, and cerebral blood flow supply of patients with VCIND. 

PMID- 25966265
TI  - Identification and expression analysis of the MSP130-related-2 gene from
      Hyriopsis cumingii.
AB  - MSP130-related-2 is thought to play a role in bio-mineralization as revealed in
      Crassostrea gigas and sea urchins. In this study, an MSP130-related-2 gene was
      isolated from Hyriopsis cumingii (HcMSP130-related-2) and characterized for the
      first time. The HcMSP130-related-2 cDNA was 2307 bp in length and consisted of a
      572-bp 5'-untranslated region (5'-UTR), a 1239-bp open reading frame encoding 430
      amino acid residues, and a 439-bp 3'-UTR. The molecular weight of the peptide was
      predicted to be 48551.3 Da, with a theoretical isoelectric point of 4.78 and
      instability index of 32.74, indicating that the protein is stable. The HcMSP130
      related-2 amino acid residues included a signal peptide and several potential N
      glycosylation sites. NCBI BLAST analysis indicated that this full-length amino
      acid sequence showed the highest similarity with HcMSP130-related-2 from C. gigas
      (45%) and about 38% identity with that from SpMSP130-rel-2 and Strongylocentrotus
      purpuratus. A phylogenetic tree showed that HcMSP130-rel-2 clustered with MSP130
      from C. gigas. HcMSP130-related-2 was expressed in various tissues, including the
      mantle, blood, gill, foot, liver, kidney, intestine, and muscle, with the highest
      transcripts found in the mantle. Quantitative real-time polymerase chain reaction
      was used to analyze the expression of the HcMSP130- related-2 gene in grass carp
      after inducing shell damage. HcMSP130- related-2 expression was upregulated
      significantly in the mantle within 7 days (P < 0.05) after damage; however, the
      expression remained unchanged in the adductor muscle tissues (P > 0.05). These
      data suggest that HcMSP130-related-2 might be involved in shell formation in H.
      cumingii. 

PMID- 25966266
TI  - Clinical analysis of penehyclidine hydrochloride combined with hemoperfusion in
      the treatment of acute severe organophosphorus pesticide poisoning.
AB  - This study aimed to observe the clinical curative effect of penehyclidine
      hydrochloride (PHC) combined with hemoperfusion in treating acute severe
      organophosphorus pesticide poisoning. We randomly divided 61 patients with severe
      organophosphorus pesticide poisoning into an experimental group (N = 31) and a
      control group (N = 30), and we compared the coma-recovery time, mechanical
      ventilation time, healing time, hospital expenses, and mortality between the two
      groups. The coma-recovery time, mechanical ventilation time, and healing time
      were lower in the experimental group than in the control group (P < 0.05), while
      the hospitalization expenses were higher in the experimental group than in the
      control group (P < 0.01); moreover, no significant difference was observed in the
      mortality rate between the two groups. Thus, PHC combined with hemoperfusion
      exerts a better therapeutic effect in acute severe organophosphorus pesticide
      poisoning than PHC alone. 

PMID- 25966267
TI  - Molecular characterization of the endophytic fungal community associated with
      Eichhornia azurea (Kunth) and Eichhornia crassipes (Mart.) (Pontederiaceae)
      native to the Upper Parana River floodplain, Brazil.
AB  - Endophytic fungi live in the interior of healthy plants without causing them any
      damage. These fungi are of biotechnological interest; they may be used in the
      biological control of pests and plant diseases, and in the pharmaceutical
      industry. The aquatic macrophytes Eichhornia azurea (Kunth) and Eichhornia
      crassipes (Mart.) belong to the Pontederiaceae family. The first is a fixed
      floating species and the second is a free-floating species that is known for its
      phytoremediation potential. The fungal endophytes associated with the leaves of
      E. azurea and E. crassipes, native to the Upper Parana River floodplain, Brazil,
      were isolated. The sequencing of the ITS1-5.8S-ITS2 region of ribosomal DNA was
      performed and the nucleotide sequences obtained were compared with those
      available in the GenBank database for the molecular identification of the
      isolates. The construction of phylogenetic trees was performed using the MEGA5
      software. The results showed that high colonization frequencies were obtained
      from the 610 foliar fragments sampled from each plant: 87.86% for E. azurea and
      88.85% for E. crassipes. At the genus level, it was possible to identify 19
      fungal endophytes belonging to the genera Alternaria, Bipolaris, Cercospora,
      Diaporthe, Gibberella, Pestalotiopsis, Plectosphaerella, Phoma, and Saccharicola.
      Two other endophytes were identified at the species level (Microsphaeropsis
      arundinis). Genera Bipolaris, Cercospora, Microsphaeropsis, and Phoma were found
      as endophytes in the two macrophytes and the other genera were host-specific,
      being isolated from only one macrophyte, proving that there is a small difference
      in the endophytic diversity of the two Eichhornia species analyzed. 

PMID- 25966268
TI  - Changes in peripheral blood natural killer T cells in hepatitis B e antigen
      positive chronic hepatitis B patients and efficacy prediction after pegylated
      interferon therapy.
AB  - We examined the expression of peripheral blood natural killer T (NKT) cells in
      hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients and
      predicted its efficacy after pegylated interferon alpha-2a (Peg-INFalpha-2a)
      therapy. Sixty-three cases of HbeAg-positive CHB inpatients and outpatients,
      treated in the Third Xiangya Hospital of Central South University from January to
      December 2010, were administrated Peg-INFalpha-2a 18 myriad international unit
      intramuscularly once per week for 48 weeks. The number of peripheral NKT cells, 5
      quantitative indicators of hepatitis B, and hepatitis B virus DNA capacity were
      detected at each time point. Forty-eight weeks after Peg-INFalpha-2a treatment,
      26 HBeAg-positive CHB patients exhibited significant effects, 21 cases exhibited
      effects, and 16 cases showed no effects. The ratio of peripheral blood NKT cells
      in T lymphocytes before and 4, 8, and 12 weeks after treatment in the significant
      effect group was significantly increased compared to the effect group and no
      effect group (P < 0.01); at the 48th week of treatment and 24 weeks after the
      drug was withdrawn, NKT cell expression in the significant effect group was
      significantly higher than that in the effect group (t = 32.0, P < 0.01; t = 27.6,
      P < 0.01, respectively). A total of 27 patients showed HBeAg seroconversion until
      the 24th week after drug withdrawal. During treatment with Peg-INFalpha-2a in
      HBeAg-positive CHB patients, expression of peripheral blood NKT cells could be
      used to predict efficacy. 

PMID- 25966269
TI  - Salt stress represses production of extracellular proteases in Bacillus pumilus.
AB  - Bacillus pumilus is able to secrete subtilisin-like prote-ases, one of which has
      been purified and characterized biochemically, demonstrating great potential for
      use in industrial applications. In the current study, the biosynthesis and
      transcription of extracellular pro-teases in B. pumilus (BA06) under salt stress
      were investigated using various methods, including a proteolytic assay, zymogram
      analysis, and real-time PCR. Our results showed that total extracellular
      proteolytic activity, both in fermentation broth and on milk-containing agar
      plates, was considerably repressed by salt in a dosage-dependent manner. As
      Bacillus species usually secret multiple extracellular proteases, a vari-ety of
      individual extracellular protease encoding genes were selected for real-time PCR
      analysis. It was shown that proteases encoded by the aprE and aprX genes were the
      major proteases in the fermentation broth in terms of their transcripts in B.
      pumilus. Further, transcription of aprE, aprX, and epr genes was indeed repressed
      by salt stress. In con-trast, transcription of other genes (e.g., vpr and wprA)
      was not repressed or significantly affected by the salt. Conclusively, salt
      stress represses total extracellular proteolytic activity in B. pumilus, which
      can largely be ascribed to suppression of the major protease-encoding genes
      (aprE, aprX) at the transcriptional level. In contrast, transcription of other
      pro-tease-encoding genes (e.g., vpr, wprA) was not repressed by salt stress. 

PMID- 25966270
TI  - Low-level sequence variation in Toxoplasma gondii calcium-dependent protein
      kinases among different genotypes.
AB  - The causative agent of toxoplasmosis, Toxoplasma gondii, can infect virtually all
      nucleated cell types of warm-blooded animals. In this study, we examined the
      sequence variation in calcium-dependent protein kinase 2 (CDPK2) genes among 13
      T. gondii strains from different hosts and geographical locations. The results
      showed that the lengths of the complete CDPK2 DNA and cDNA sequences were 3671
      3673 and 2136 bp, respectively, and the sequence variation was 0-0.9% among
      different T. gondii strains. Phylogenetic analysis based on the CDPK2 gene
      sequences revealed that T. gondii strains of the same genotypes were clustered in
      different clades. Further analysis of all the other T. gondii CDPK genes in
      genotype I (GT1), II (ME49), or III (VEG) strains indicated the T. gondii CDPK
      gene family is quite conserved, with sequence variation ranging from 0 to 1.40%.
      We concluded that CDPK2 as well as all the other CDPK genes in T. gondii cannot
      be used as proper markers for studying the variants of different T. gondii
      genotypes from different hosts and geographical locations, but their sequence
      conservation may be a useful feature promoting them as anti-T. gondii vaccine
      candidates in further studies. 

PMID- 25966272
TI  - TNF-alpha -308 A/G and -238 A/G polymorphisms and susceptibility to glaucoma: a
      meta-analysis.
AB  - The purpose of this study was to examine whether tu-mor necrosis factor-alpha
      (TNF-alpha) -308 A/G and -238 A/G polymorphisms confer susceptibility to
      glaucoma. A meta-analysis was conducted ex-amining the association between TNF
      alpha -308 A/G and -238 A/G poly-morphisms and glaucoma. A total of 13 studies on
      TNF-alpha -308 A/G and 238 A/G polymorphisms were included in this meta-analysis.
      The meta-analysis revealed no association between the TNF-alpha -308 A al-lele
      and glaucoma [odds ratio (OR) = 1.403, 95% confidence inter-val (CI) = 0.784
      2.513, P = 0.254]. Subgroup analysis by disease type revealed no association
      between the TNF-alpha -308 A allele and glau-coma. The meta-analysis revealed no
      significant association between the TNF-alpha -238 A allele and glaucoma (OR =
      1.120, 95%CI = 0.708-1.773, P = 0.628). This meta-analysis showed no association
      between the A alleles of the TNF-alpha -308 A/G or -238 A/G polymorphisms and
      glaucoma. 

PMID- 25966271
TI  - Efficacy of Artemisia annua polysaccharides as an adjuvant to hepatitis C
      vaccination.
AB  - The traditional Chinese medicine Artemisia annua can prevent and treat hepatitis
      following an unclear mechanism. The aim of this study was to evaluate the effects
      of A. annua polysaccharides (AAP) on hepatitis C virus (HCV). A pcDNA3.1/NS3
      expression vector was constructed. Ninety female BALB/c mice were randomly
      divided into six groups: high-dose AAP (1 mg/mL) + HCV/NS3 plasmid; middle-dose
      AAP (0.5 mg/mL) + HCV/NS3 plasmid; low-dose AAP (0.1 mg/mL) + HCV/NS3 plasmid;
      HCV/NS3 plasmid; high-dose AAP (1 mg/mL); normal saline control (N = 15). Except
      the control group and the high-dose AAP group, other groups were inoculated with
      50 MUg pcDNA3.1-HCV/NS3 plasmid. Serum antigenic-specific antibody was detected
      after the last immunization, and the levels of secreted IFN-gamma and IL-4 were
      measured. pcDNA3.1/NS3 plasmid was successfully constructed, and the extracted
      product contained HCV/NS3 sequence. Compared with single inoculation with HCV/NS3
      DNA vaccine, the specific antibody levels induced by middle-dose AAP plus HCV/NS3
      DNA vaccine were significantly different in weeks 1, 3 and 5 (P < 0.05). However,
      there were no significant differences in the antibody levels induced by high-dose
      and low-dose AAP as adjuvant compared with those of single inoculation with DNA
      vaccine (P > 0.05). The level of serum IFN-gamma secretion was significantly
      higher than that of IL-4 secretion. Compared with the single HCV/NS3 DNA vaccine
      group, AAP plus HCV/NS3 DNA vaccine groups had significant increased IFN-gamma
      levels (P < 0.05), but the IL-4 levels were not significantly different among
      these groups (P > 0.05). AAP, as the adjuvant of HCV/NS3 DNA vaccine, can widely
      regulate the humoral immunity and cellular immune function of normal and
      cyclophosphamide-induced immunocompromised mice. AAP can promote IFN-gamma
      secretion probably by inducing Th1-type cellular immune response. 

PMID- 25966273
TI  - Codon optimization enhances the expression of porcine beta-defensin-2 in
      Escherichia coli.
AB  - Porcine beta-defensin-2 (pBD2) is a cationic antimicrobial peptide that has
      therapeutic potential. The amount of pBD2 in nature is limited, and the
      expression of pBD2 in Escherichia coli is low, probably because a different gene
      codon is used by prokaryotic organisms to that used by eukaryotes. Codon
      preference optimization is one of the ways to increase heterologous expression of
      pBD2. To achieve high expression of pBD2, the pBD2 gene was redesigned according
      to the preferred codon in E. coli without altering the amino acid sequence. The
      optimized gene was inserted into expression vector pET-30a and transformed into
      E. coli BL21 (DE3) plysS. Our results showed that pBD2 was expressed as His-Tag
      fusion protein at a level that was approximately 4-6 times greater than from the
      native gene, based on total protein expression. Expressed fusion pBD2 showed
      antimicrobial activity against both E. coli and Staphylococcus aureus. Moreover,
      pBD2 showed weak hemolytic activity and strong heat resistance. These results
      indicate that fusion pBD2 is functional and has similar properties to those of
      pBD2 from the native gene. Our current study demonstrated that codon optimization
      could enhance pBD2 expression in E. coli without altering its function.
      Therefore, the expression of pBD2 after codon optimization in heterologous host
      cells might be useful and is worthy of further research. 

PMID- 25966274
TI  - Mangiferin induces cell cycle arrest at G2/M phase through ATR-Chk1 pathway in HL
      60 leukemia cells.
AB  - This study aimed to determine the effect of mangiferin on the cell cycle in HL-60
      leukemia cells and expression of the cell cycle-regulatory genes Wee1, Chk1 and
      CDC25C and to further investigate the molecular mechanisms of the antileukemic
      action of mangiferin. The inhibitory effect of mangiferin on HL-60 leukemia cell
      proliferation was determined by the MTT assay. The impact of mangiferin on the HL
      60 cell cycle was evaluated by flow cytometry. After the cells were treated with
      different concentrations of mangiferin, the expression levels of Wee1, Chk1 and
      CDC25C mRNA were determined by RT-PCR, and Western blot was used to evaluate the
      expression levels of cdc25c, cyclin B1, and Akt proteins. The inhibition of HL-60
      cell growth by mangiferin was dose- and time-dependent. After treatment for 24 h,
      cells in G2/M phase increased, and G2/M phase arrest appeared with increased mRNA
      expression of Wee1, Chk1 and CDC25C. Mangiferin inhibited Chk1 and cdc25c mRNA
      expression at high concentrations and induced Wee1 mRNA expression in a dose
      dependent manner. It significantly inhibited ATR, Chk1, Wee1, Akt, and ERK1/2
      phosphorylation but increased cdc2 and cyclin B1 phosphorylation. Furthermore,
      mangiferin reduced cdc25c, cyclin B1, and Akt protein levels while inducing Wee1
      protein expression. It also antagonized the phosphorylation effect of vanadate on
      ATR, and the phosphorylation effect of EGF on Wee1. These findings indicated that
      mangiferin inhibits cell cycle progression through the ATR-Chk1 stress response
      DNA damage pathway, leading to cell cycle arrest at G2/M phase in leukemia cells.

PMID- 25966275
TI  - Sperm aneuploidy and implications for genetic counseling in a pedigree of three
      t(1;3) balanced translocation carriers.
AB  - A reciprocal translocation between the short arm of chromosome 1 and the long arm
      of chromosome 3 was observed in a pedigree of three carriers (proband, and his
      brother and mother). In this study, the three carriers had different clinical
      manifestations: the proband with infertility, his brother with spousal
      miscarriages, and his mother with no adverse reproductive history. Cytogenetic
      analysis of metaphase chromosomes was performed, and triple-color fluorescence in
      situ hybridization was applied to the detection of aneuploidy sperm related to
      the interchromosomal effect (ICE). An increase of aneuploidy of chromosome 21 in
      the proband and aneuploidy of chromosomes 13, 21, and Y in the brother were
      observed. Since patients with reciprocal translocations and spermatogenetic
      impairment are candidates, with their partners, for intracytoplasmic sperm
      injection, the study of the level of sperm aneuploidy rates would provide useful
      information for couples at risk, as well as contributing to a better
      understanding of the ICE. 

PMID- 25966276
TI  - Expression analysis of dihydroflavonol 4-reductase genes in Petunia hybrida.
AB  - Dihydroflavonol 4-reductase (DFR) genes from Rosa chinensis (Asn type) and
      Calibrachoa hybrida (Asp type), driven by a CaMV 35S promoter, were integrated
      into the petunia (Petunia hybrida) cultivar 9702. Exogenous DFR gene expression
      characteristics were similar to flower-color changes, and effects on anthocyanin
      concentration were observed in both types of DFR gene transformants. Expression
      analysis showed that exogenous DFR genes were expressed in all of the tissues,
      but the expression levels were significantly different. However, both of them
      exhibited a high expression level in petals that were starting to open. The
      introgression of DFR genes may significantly change DFR enzyme activity.
      Anthocyanin ultra-performance liquid chromatography results showed that
      anthocyanin concentrations changed according to DFR enzyme activity. Therefore,
      the change in flower color was probably the result of a DFR enzyme change.
      Pelargonidin 3-O-glucoside was found in two different transgenic petunias,
      indicating that both CaDFR and RoDFR could catalyze dihydrokaempferol. Our
      results also suggest that transgenic petunias with DFR gene of Asp type could
      biosynthesize pelargonidin 3-O-glucoside. 

PMID- 25966277
TI  - Association of TUSC3 gene polymorphisms with non-syndromic mental retardation
      based on nuclear families in the Qinba mountain area of China.
AB  - TUSC3 interacts with the protein phosphatase 1 and magnesium ion transport
      system, which plays an important role in learning and memory. Abnormal conditions
      of learning and memory are common clinical characteristics of mental retardation
      (MR). However, the association of TUSC3 genetic polymorphisms with MR remains
      unknown. A total of 456 DNA samples including 174 nuclear families containing MR
      were collected in the Qinba mountain area of China. The genotypes of eight tag
      single nucleotide polymorphisms of TUSC3 were evaluated with traditional genetic
      methods. Family-based association tests, transmission disequilibrium tests
      (TDTs), and haplotype relative risk (HRR) analyses were performed to investigate
      the association between genetic variants of the TUSC3 gene and MR. The genetic
      polymorphisms rs10093881, rs6530893, and rs6994908 were associated with MR (all P
      values <0.05) based upon the results of single-site TDT and HRR analyses. The
      haplotype block consisting of rs6530893 and rs6994908, harboring the sixth exon
      of TUSC3, was also associated with MR (all P values <0.05). This study
      demonstrated an association between genetic polymorphisms of the TUSC3 gene and
      MR in the Qinba mountain area, the sixth exon of which might contribute to the
      risk of MR. However, further studies are needed on the causal mechanisms in this
      association. 

PMID- 25966279
TI  - Fear expression and return of fear following threat instruction with or without
      direct contingency experience.
AB  - Prior research showed that mere instructions about the contingency between a
      conditioned stimulus (CS) and an unconditioned stimulus (US) can generate fear
      reactions to the CS. Little is known, however, about the extent to which actual
      CS-US contingency experience adds anything beyond the effect of contingency
      instructions. Our results extend previous studies on this topic in that it
      included fear potentiated startle as an additional dependent variable and
      examined return of fear (ROF) following reinstatement. We observed that CS-US
      pairings can enhance fear reactions beyond the effect of contingency
      instructions. Moreover, for all measures of fear, instructions elicited immediate
      fear reactions that could not be completely overridden by subsequent situational
      safety information. Finally, ROF following reinstatement for instructed CS+s was
      unaffected by actual experience. In summary, our results demonstrate the power of
      contingency instructions and reveal the additional impact of actual experience of
      CS-US pairings.

PMID- 25966278
TI  - Progressive cognitive deficit, motor impairment and striatal pathology in a
      transgenic Huntington disease monkey model from infancy to adulthood.
AB  - One of the roadblocks to developing effective therapeutics for Huntington disease
      (HD) is the lack of animal models that develop progressive clinical traits
      comparable to those seen in patients. Here we report a longitudinal study that
      encompasses cognitive and motor assessment, and neuroimaging of a group of
      transgenic HD and control monkeys from infancy to adulthood. Along with
      progressive cognitive and motor impairment, neuroimaging revealed a progressive
      reduction in striatal volume. Magnetic resonance spectroscopy at 48 months of age
      revealed a decrease of N-acetylaspartate (NAA), further suggesting neuronal
      damage/loss in the striatum. Postmortem neuropathological analyses revealed
      significant neuronal loss in the striatum. Our results indicate that HD monkeys
      share similar disease patterns with HD patients, making them potentially suitable
      as a preclinical HD animal model. 

PMID- 25966281
TI  - Exploring the role of multiple chronic conditions in traditional Chinese medicine
      use and three types of traditional Chinese medicine therapy among adults in
      Taiwan.
AB  - INTRODUCTION: Numerous people with chronic conditions like to use traditional
      Chinese medicine (TCM) treatment, or integrated treatment of TCM and Western
      medicine (WM). Our study explored the associations between multiple chronic
      conditions (MCC) and TCM use and the use of specific types of TCM therapy among
      adults in Taiwan. In addition, we explored the TCM use of adults with seven
      common types of chronic conditions. METHODS: In our study, a national
      representative sample in 2005 was used. The Chronic Condition Indicator and the
      Clinical Classifications System created by the U.S. Agency for Healthcare
      Research and Quality were used to define the number of chronic conditions of
      adults. Logistic regressions adjusted for demographic characteristics were used
      to analyze the associations. The frequency of TCM use among adults with different
      numbers of chronic conditions was quantified. RESULTS: TCM use for adults with
      >=5 chronic conditions (odds ratio [OR] 1.86) was higher than TCM use for adults
      with 2-4 chronic conditions (OR 1.51) and TCM use for adults with one chronic
      condition (OR 1.48). The increase in the OR of the use of Chinese herbs and
      traumatology manipulative therapy according to the number of chronic conditions
      was not as substantial as that of acupuncture-moxibustion. The frequency of TCM
      use exhibited an increasing trend with the increase in the number of chronic
      conditions (p<.001). Among the seven common types of chronic conditions for
      adults, TCM use for adults with arthropathy (OR 2.01) was the highest.
      CONCLUSION: The probability and frequency of TCM use increased as the number of
      chronic conditions increased. The probability of Chinese herbs use, traumatology
      manipulative therapy use, and, particularly, acupuncture-moxibustion use
      increased as the number of chronic conditions increased. We suggest that
      government policy makers emphasize administering integrated TCM and WM care to
      people with chronic conditions or MCC.

PMID- 25966280
TI  - AXL is an oncotarget in human colorectal cancer.
AB  - AXL is a tyrosine kinase receptor activated by GAS6 and regulates cancer cell
      proliferation migration and angiogenesis. We studied AXL as new therapeutic
      target in colorectal cancer (CRC). Expression and activation of AXL and GAS6 were
      evaluated in a panel of human CRC cell lines. AXL gene silencing or pharmacologic
      inhibition with foretinib suppressed proliferation, migration and survival in CRC
      cells. In an orthotopic colon model of human HCT116 CRC cells overexpressing AXL,
      foretinib treatment caused significant inhibition of tumour growth and peritoneal
      metastatic spreading. AXL and GAS6 overexpression by immunohistochemistry (IHC)
      were found in 76,7% and 73.5%, respectively, of 223 human CRC specimens,
      correlating with less differentiated histological grading. GAS6 overexpression
      was associated with nodes involvement and tumour stage. AXL gene was found
      amplified by Fluorescence in situ hybridization (FISH) in 8/146 cases (5,4%) of
      CRC samples. Taken together, AXL inhibition could represent a novel therapeutic
      approach in CRC. 

PMID- 25966282
TI  - Polar diketopyrrolopyrrole-imidazolium salts as selective probes for staining
      mitochondria in two-photon fluorescence microscopy.
AB  - Three rationally designed polar derivatives of diketopyrrolopyrrole consisting of
      1,3-dimethylimidazolium cationic units and benzene, thiophene, or furan rings as
      pi spacers were synthesized and thoroughly studied. The obtained salts are
      soluble in polar organic solvents and show satisfactory solubility in water,
      which makes them suitable for the applications in bioimaging. Photophysical
      measurements revealed that the obtained derivatives are characterized by strong
      absorption and good fluorescence quantum yields. The corresponding two-photon
      properties were also examined and showed that the synthesized salts exhibit large
      two-photon absorption cross-sections reaching 4000 GM (GM=Goeppert-Mayer unit, 1
      GM=10(-50)  cm(4)  s photon(-1) ) and very high two-photon brightness values
      exceeding 2000 GM. It was demonstrated that these salts can be safely applied in
      two-photon fluorescence microscopy for selective staining of mitochondria in
      living cells. 

PMID- 25966283
TI  - Improved method for roadside barrier length of need modeling using real-world
      trajectories.
AB  - The 2011 AASHTO Roadside Design Guide (RDG) contains perhaps the most widely used
      procedure for choosing an appropriate length of need (LON) for roadside barriers.
      However, this procedure has several limitations. The procedure uses a highly
      simplified model of vehicle departure, and the procedure does not allow designers
      to specify an explicit level of protection. A new procedure for choosing LON that
      addresses these limitations is presented in this paper. This new procedure is
      based on recent, real-world road departure trajectories and uses this departure
      data in a more realistic way. The new procedure also allows LON to be specified
      for a precisely known level of protection - a level which can be based on number
      of crashes, injury outcomes or even estimated crash cost - while still remaining
      straightforward and quick to use like the 2011 RDG procedure. In this analysis,
      the improved procedure was used to explore the effects of the RDG procedure's
      assumptions. LON recommendations given by the 2011 RDG procedure were compared
      with recommendations given by this improved procedure. For 55 mph roads, the 2011
      RDG procedure appears to lead to a LON sufficient to intercept between 80% and
      90% of right-side departures that would otherwise strike a hazard located 10 m
      from the roadway. For hazards closer than 10 m, the 2011 RDG procedure intercepts
      progressively higher percentages of real-world departures. This suggests the
      protection level provided by the 2011 RDG procedure varies with the hazard
      offset, becoming more conservative as the hazard moves closer to the roadway. The
      improved procedure, by comparison, gives a consistent protection level regardless
      of hazard location.

PMID- 25966285
TI  - Theoretical Analysis of the Mechanism of Fracture Network Propagation with
      Stimulated Reservoir Volume (SRV) Fracturing in Tight Oil Reservoirs.
AB  - Stimulated reservoir volume (SRV) fracturing in tight oil reservoirs often
      induces complex fracture-network growth, which has a fundamentally different
      formation mechanism from traditional planar bi-winged fracturing. To reveal the
      mechanism of fracture network propagation, this paper employs a modified
      displacement discontinuity method (DDM), mechanical mechanism analysis and
      initiation and propagation criteria for the theoretical model of fracture network
      propagation and its derivation. A reasonable solution of the theoretical model
      for a tight oil reservoir is obtained and verified by a numerical discrete
      method. Through theoretical calculation and computer programming, the variation
      rules of formation stress fields, hydraulic fracture propagation patterns (FPP)
      and branch fracture propagation angles and pressures are analyzed. The results
      show that during the process of fracture propagation, the initial orientation of
      the principal stress deflects, and the stress fields at the fracture tips change
      dramatically in the region surrounding the fracture. Whether the ideal fracture
      network can be produced depends on the geological conditions and on the
      engineering treatments. This study has both theoretical significance and
      practical application value by contributing to a better understanding of fracture
      network propagation mechanisms in unconventional oil/gas reservoirs and to the
      improvement of the science and design efficiency of reservoir fracturing. 

PMID- 25966284
TI  - Comparative hazard identification by a single dose lung exposure of zinc oxide
      and silver nanomaterials in mice.
AB  - Comparative hazard identification of nanomaterials (NMs) can aid in the
      prioritisation for further toxicity testing. Here, we assessed the acute lung,
      systemic and liver responses in C57BL/6N mice for three NMs to provide a hazard
      ranking. A silver (Ag), non-functionalised zinc oxide (ZnO) and a
      triethoxycaprylylsilane functionalised ZnO NM suspended in water with 2% mouse
      serum were examined 24 hours following a single intratracheal instillation
      (I.T.). An acute pulmonary inflammation was noted (marked by a polymorphonuclear
      neutrophil influx) with cell damage (LDH and total protein) in broncho-alveolar
      lavage fluid (BALF) after administration of both non-functionalised and
      functionalised ZnO. The latter also induced systemic inflammation measured as an
      increase in blood neutrophils and a decrease in blood lymphocytes. Exposure to Ag
      NM was not accompanied by pulmonary inflammation or cytotoxicity, or by systemic
      inflammation. A decrease in glutathione levels was demonstrated in the liver
      following exposure to high doses of all three nanomaterials irrespective of any
      noticeable inflammatory or cytotoxic effects in the lung. By applying benchmark
      dose (BMD) modeling statistics to compare potencies of the NMs, we rank
      functionalised ZnO ranked the highest based on the largest number of affected
      endpoints, as well as the strongest responses observed after 24 hours. The non
      functionalised ZnO NM gave an almost similar response, whereas Ag NM did not
      cause an acute response at similar doses. 

PMID- 25966286
TI  - The Transcription Factor CarH Safeguards Use of Adenosylcobalamin as a Light
      Sensor by Altering the Photolysis Products.
AB  - The newly discovered light-dependent transcription factor CarH uses
      adenosylcobalamin as a light sensor to regulate expression of protective genes in
      bacteria upon exposure to sunlight. This use of adenosylcobalamin is a clever
      adaptation of a classic enzyme cofactor, taking advantage of its photolabile Co-C
      bond. However, it is also puzzling in that photolysis of adenosylcobalamin
      generates the 5'-deoxyadenosyl radical that could damage DNA. Here, using liquid
      chromatography and spectroscopic techniques, we demonstrate that CarH suppresses
      release of the 5'-deoxyadenosyl radical and instead effects conversion to a
      nonreactive 4',5'-anhydroadenosine. In this manner, CarH safeguards use of
      adenosylcobalamin in light-dependent gene regulation. 

PMID- 25966287
TI  - Correction: The Predictive Value of the Boston Acute Stroke Imaging Scale (BASIS)
      in Acute Ischemic Stroke Patients among Chinese Population.

PMID- 25966288
TI  - Endovascular aneurysm repair with the Ovation TriVascular Stent Graft System
      utilizing a predominantly percutaneous approach under local anaesthesia.
AB  - OBJECTIVE: To present our experience with the Ovation Abdominal Stent Graft
      System (TriVascular Inc., Santa Rosa, CA) during endovascular aneurysm repair
      (EVAR) and compare results according to the type of anaesthesia. METHODS: We
      conducted a single-centre retrospective study including patients who underwent
      EVAR using the Ovation endograft between May 2011 and July 2014. Outcome was
      evaluated regarding pre-, peri- and immediate postoperative and follow-up
      measures. Overall results are reported, while additional analysis was performed
      to compare the outcome between groups of patients undertaking either local or
      regional/general anaesthesia (LA vs RGA). RESULTS: 66 patients were included.
      Median follow-up was 13 months (range, 1-39 months). Median age was 72 years and
      median abdominal aortic aneurysm diameter was 58 mm (range, 54-100 mm). Technical
      success was 63 (95%), while there were 2 (3%) conversions to open surgery. A
      total percutaneous approach was used in 50/66 (76%) cases. Overall, 9/66 (14%)
      subjects suffered from any kind of morbidity. Median hospitalization was 3 days
      (range, 1-16 days). Immediate and midterm mortality rate was 0%. No endoleak Type
      I, III, IV or stent migration was observed. There were 8 (13%) Type II endoleaks.
      Overall, additional endovascular procedures were required in 6 (9%), while
      surgery was performed in 4 (6%) patients. 44 (67%) patients underwent LA and 22
      (23%) RGA. Differences between groups were significant for procedural time (85 vs
      107 min; p < 0.001), percutaneous access (91% vs 45%; p < 0.001) and systematic
      complications (2.3% vs 14%; p = 0.05). CONCLUSION: EVAR with the use of the
      Ovation endograft shows promising short-term and midterm results regarding safety
      and effectiveness. Completion of the procedures under LA using a total
      percutaneous approach seems advantageous and may be used in routine practice.
      ADVANCES IN KNOWLEDGE: The Ovation Abdominal Stent Graft System is an ultra-low
      profile stent graft system that allows percutaneous deployment for EVAR and
      offers excellent overall efficacy and safety. Totally percutaneous EVAR under LA
      seems advantageous and may be used as a routine with this specific endograft.

PMID- 25966289
TI  - CT imaging spectrum and the histopathological features of adult metanephric
      adenoma.
AB  - OBJECTIVE: To retrospectively evaluate the radiopathological features of adult
      metanephric adenoma (MA) and explore whether MA can be differentiated on CT
      images, including the basis of their morphological features and enhancement
      patterns. METHODS: 18 consecutive MA cases (age range, 18-66 years; 9 males and 9
      females) were pathologically proven and recruited in our study between January
      2004 and June 2014. Unenhanced and contrast-enhanced CT were performed and
      correlated with corresponding pathological findings to differentiate between MA
      and other renal tumours. The enhancement pattern, lesion contour and presence of
      calcifications were evaluated. RESULTS: On unenhanced CT scan, the most common (n
      = 15, 83.3%) CT imaging characteristics were the presence of homogeneity and well
      defined solid renal masses; the minority (n = 3, 16.7%) were heterogeneous or
      centrally located low-attenuation masses. Contrast-enhanced CT image revealed
      hypoattenuating heterogeneous masses with varying degrees of contrast enhancement
      in 16 (88.9%) cases, in contrast to those without increased attenuation in 2
      (11.1%) cases. Scattered calcification was found only in one case (5.6%).
      Pathological results revealed that a total of 6 (33.3%) cases had concomitant
      malignant carcinoma components; 2 (11.1%) patients had malignant MA; and pure MA
      was found in 10 cases, with a surprisingly high proportion of malignant tumours.
      CONCLUSION: The positive-predictive values of "high" enhancement seemed
      relatively characteristic for the diagnosis of malignant and composite MA.
      ADVANCES IN KNOWLEDGE: Radiopathological features of adult MA and exploring
      whether MA can be differentiated on CT images, including the basis of their
      morphological features and enhancement patterns.

PMID- 25966290
TI  - Radiographers' performance in chest X-ray interpretation: the Nigerian
      experience.
AB  - OBJECTIVE: To assess the performance of Nigerian radiographers in interpretation
      of plain chest radiographs and to assess whether age, years since qualification
      and sector of practice are associated with performance. METHODS: A test set of 50
      radiographs containing 23 cases with no pathology (normal) and 27 abnormal cases
      (cardiopulmonary conditions) independently confirmed by 3 radiologists were
      presented to 51 radiographers in a random order. Readers independently evaluated
      radiographs for absence or presence of disease and stated the location,
      radiographic features and diagnosis. Readers self-reported their age, years since
      qualification and sector of practice. Receiver operating characteristic was used
      to assess the performance. Mann-Whitney U test was used to assess whether age,
      years since qualification and sector of practice were associated with
      performance. RESULTS: Mean location sensitivity was 88.9 [95% confidence interval
      (CI), 0.787-0.980]. Mean sensitivity and specificity were 76.9 (95% CI, 0.658
      0.864) and 79.8 (95% CI, 0.658-0.864), respectively. Age was not associated with
      performance (p = 0.07). Number of years qualified as radiographer (p = 0.005) and
      private practice (p = 0.004) were positively associated with performance.
      CONCLUSION: Nigerian radiographers can correctly report chest radiographs to a
      reasonable standard, and performance is associated with number of years since
      qualification and the sector of practice. ADVANCES IN KNOWLEDGE: There are less
      than 300 radiologists serving a Nigerian population of about 170 million;
      therefore, X-ray interpretation by radiographers deserves consideration. Nigerian
      radiographers have potential to interpret chest X-ray in the clinical setting,
      and this may significantly improve radiology service delivery in this region.

PMID- 25966293
TI  - Bridging the divide: advances and challenges in understanding the impact of race
      and ethnicity on the mental health of older adults.

PMID- 25966292
TI  - Efficacy of an opposite position aspiration on resolution of pneumothorax
      following CT-guided lung biopsy.
AB  - OBJECTIVE: To evaluate the efficacy of aspiration in an opposite position to deal
      with pneumothorax after CT-guided lung biopsy. METHODS: A retrospective study was
      developed involving 210 patients with pneumothorax who had undergone CT-guided
      percutaneous core biopsies from January 2012 to March 2014 for various pulmonary
      lesions. Asymptomatic patients with minimal pneumothorax were treated
      conservatively. Simple manual aspiration was performed for symptomatic patients
      with minimal pneumothorax and for all patients with moderate to large
      pneumothorax. An opposite position aspiration was performed when simple manual
      aspiration failed. The efficacy of simple manual aspiration and the opposite
      position aspiration was observed. RESULTS: Among 210 patients with pneumothorax,
      128 (61.0%) asymptomatic patients with minimal pneumothorax were treated
      conservatively. The remaining 82 were treated with attempted simple manual
      aspiration. Out of these 82 patients, simple manual aspiration was successful in
      58 (70.7%, 58/82) cases. The complete and partial regression rates were 17.2%
      (10/58) and 82.8% (48/58), respectively. In the other 24 patients (29.3%, 24/82),
      simple aspiration technique was ineffective. An opposite position (from prone to
      supine or vice versa) was applied, and a new biopsy puncture site was chosen for
      reaspiration. This procedure was successful in 22 patients but not in 2 patients
      who had to have a chest tube insertion. The complete and partial regression rates
      were 25.0% (6/24) and 66.7% (16/24), respectively. Applying the new method, the
      total effective rate of aspiration improved significantly from 70.7% (58/82) to
      97.6% (80/82). CONCLUSION: The opposite position aspiration can be safe,
      effective and minimally invasive treatment for CT-guided lung biopsy-induced
      pneumothorax thus reducing the use of chest tube significantly. ADVANCES IN
      KNOWLEDGE: (1) Opposite position aspiration can elevate the success rate of
      aspiration significantly (from 70.7% to 97.6% in our study); (2) this procedure
      is a safe, effective and minimally invasive treatment for pneumothorax caused by
      biopsy; and (3) opposite position aspiration is a useful technique to reduce the
      use of chest tube, which has clinical significance.

PMID- 25966291
TI  - Primary vaginal cancer: role of MRI in diagnosis, staging and treatment.
AB  - Primary carcinoma of the vagina is rare, accounting for 1-3% of all
      gynaecological malignancies. MRI has an increasing role in diagnosis, staging,
      treatment and assessment of complications in gynaecologic malignancy. In this
      review, we illustrate the utility of MRI in patients with primary vaginal cancer
      and highlight key aspects of staging, treatment, recurrence and complications. 

PMID- 25966294
TI  - Implementation of an electronic monitoring and evaluation system for the
      antiretroviral treatment programme in the Cape Winelands district, South Africa:
      a qualitative evaluation.
AB  - BACKGROUND: A pragmatic three-tiered approach to monitor the world's largest
      antiretroviral treatment (ART) programme was adopted by the South African
      National Department of Health in 2010. With the rapid expansion of the programme,
      the limitations of the paper-based register (tier 1) were the catalyst for
      implementation of the stand-alone electronic register (tier 2), which offers
      simple digitisation of the paper-based register. This article engages with theory
      on implementation to identify and contextualise enabling and constraining factors
      for implementation of the electronic register, to describe experiences and use of
      the register, and to make recommendations for implementation in similar settings
      where standardisation of ART monitoring and evaluation has not been achieved.
      METHODS: We conducted a qualitative evaluation of the roll-out of the register.
      This comprised twenty in-depth interviews with a diverse sample of stakeholders
      at facility, sub-district, and district levels of the health system. Facility
      level participants were selected across five sub-districts, including one
      facility per sub-district. Responses were coded and analysed using a thematic
      approach. An implementation science framework guided interpretation of the data.
      RESULTS & DISCUSSION: We identified the following seven themes: 1) ease of
      implementation, 2) perceived value of an electronic M&E system, 3) importance of
      stakeholder engagement, 4) influence of a data champion, 5) operational and
      logistical factors, 6) workload and role clarity, and 7) importance of
      integrating the electronic register with routine facility monitoring and
      evaluation. Interpreting our findings through an implementation theory enabled us
      to construct the scaffolding for implementation across the five facility
      settings. This approach illustrated that implementation was not a linear process
      but occurred at two nodes: at the adoption of the register for roll-out, and at
      implementation at facility-level. CONCLUSION: In this study we found that
      relative advantage of an intervention and stakeholder engagement are critical to
      implementation. We suggest that without these aspects of implementation,
      formative and summative outcomes of implementation at both the adoption and
      coalface stages of implementation would be negatively affected.

PMID- 25966295
TI  - Asymmetric damage segregation at cell division via protein aggregate fusion and
      attachment to organelles.
AB  - The segregation of damaged components at cell division determines the survival
      and aging of cells. In cells that divide asymmetrically, such as Saccharomyces
      cerevisiae, aggregated proteins are retained by the mother cell. Yet, where and
      how aggregation occurs is not known. Recent work by Zhou and collaborators shows
      that the birth of protein aggregates, under specific stress conditions, requires
      active translation, and occurs mainly at the endoplasmic reticulum. Later,
      aggregates move to the mitochondrial surface through fis1-dependent association.
      During replicative aging, aggregate association with the mother-cell mitochondria
      contributes to the asymmetric segregation of aggregates, because mitochondria in
      the daughter cell do not carry aggregates. With increasing age of mother cells,
      aggregates lose their connection to the mitochondria, and segregation is less
      asymmetric. Relating these findings to other mechanisms of aggregate segregation
      in different organisms, we postulate that fusion between aggregates and their
      tethering to organelles such as the vacuole, nucleus, ER, or mitochondria are
      common principles that establish asymmetric segregation during stress resistance
      and aging. 

PMID- 25966296
TI  - Unravelling the tunable exchange bias-like effect in magnetostatically-coupled
      two dimensional hybrid (hard/soft) composites.
AB  - Hybrid 2D hard-soft composites have been fabricated by combining soft (Co73Si27)
      and hard (NdCo5) magnetic materials with in-plane and out-of-plane magnetic
      anisotropies, respectively. They have been microstructured in a square lattice of
      CoSi anti-dots with NdCo dots within the holes. The magnetic properties of the
      dots allow us to introduce a magnetostatic stray field that can be controlled in
      direction and sense by their last saturating magnetic field. The magnetostatic
      interactions between dot and anti-dot layers induce a completely tunable exchange
      bias-like shift in the system's hysteresis loops. Two different regimes for this
      shift are present depending on the lattice parameter of the microstructures. For
      large parameters, dipolar magnetostatic decay is observed, while for the smaller
      one, the interaction between the adjacent anti-dot's characteristic closure
      domain structures enhances the exchange bias-like effect as clarified by
      micromagnetic simulations. 

PMID- 25966297
TI  - Low systolic blood pressure and high resting heart rate as predictors of outcome
      in patients with peripartum cardiomyopathy.
AB  - BACKGROUND: Patients with peripartum cardiomyopathy (PPCM) present with low blood
      pressure (SBP) often preventing uptitration of heart failure medication. We aimed
      to study prediction of risk and the contribution of high resting heart rate (HR)
      and low SBP to risk in recent onset of PPCM. METHODS: Clinical assessment with HR
      and SBP, echocardiography and laboratory results were obtained at baseline and at
      six months on 206 patients with recent onset PPCM enrolled at two tertiary care
      centers in South Africa. Poor outcome was defined as the combined endpoint of
      death, LVEF<35% or remaining in New York Heart Association (NYHA) functional
      class III/IV at six months. Complete LV recovery was defined as LVEF >= 55% at
      six months. RESULTS: Poor outcome was observed in 110 of 220 patients (53%), with
      26 patients dying at six months (12.6%). There were 98 (47.5%) patients with SBP
      <= 110 mmHg. Patients with high HR (HR >= 100) and low SBP (< 110 mmHg) tended to
      have worse outcomes than patients below the HR median and high SBP. PPCM patients
      with low SBP and high HR were less likely to be on ACE-inhibitors (n = 35, 69%
      versus n = 129, 84%, p = 0.024) and on the beta blocker carvedilol (n = 24, 47%
      versus n = 98, 64%, p = 0.047). Low SBP, high HR and left ventricular end
      diastolic diameter at baseline were predictors of poor outcome. Patients with low
      SBP and high HR had the highest mortality (p = 0.0023). CONCLUSIONS: These
      findings suggest increased risk in patients with PPCM presenting with low SBP and
      high HR on standard heart failure medication possibly having implications on HF
      management.

PMID- 25966298
TI  - Serological patterns, antibody half-life and shedding in urine of Leptospira spp.
      in naturally exposed sheep.
AB  - AIMS: To determine within-farm prevalence, longitudinal pattern of exposure
      measured by serology, antibody titre longevity and point prevalence of shedding
      in urine of Leptospira borgpetersenii serovar Hardjo and L. interrogans serovar
      Pomona in naturally infected sheep on a sample of commercial farms in New
      Zealand. METHODS: On eight commercial sheep farms, between September 2011 and
      January 2014, blood samples were collected from 115-217 ewe lambs on each farm,
      at intervals of 2-11 months. They were analysed by microscopic agglutination test
      (MAT) for antibodies to L. borgpetersenii serovar Hardjo and L. interrogans
      serovar Pomona, using a titre cut-point of 48. Urine from 98 animals was tested
      by quantitative PCR (qPCR). The half-life of antibodies was estimated in 185
      sheep for serovar Hardjo and 21 for Pomona, and the seroprevalence and mean titre
      of animals lost to follow-up was compared with those remaining in the study.
      RESULTS: Within-flock seroprevalence for serovar Hardjo reached a maximum at 17
      22 months of age, ranging from 79 to 100%. Seroprevalence for serovar Pomona rose
      above 10% on three farms and increased to 21-54% by 4-14 months. Seroconversions
      occurred mainly from late autumn to early summer at 7-15 months of age.
      Seroprevalences ranging from 3 to 76% for serovar Hardjo and 0.5 to 15% for
      serovar Pomona were observed up to 3 months of age, likely due to maternally
      derived immunity. The half-life of antibody in response to infection was
      estimated to be 6.7 (95% CI=5.8-7.9) months for serovar Hardjo and 6.3 (95%
      CI=4.8-9.0) months for Pomona. The prevalence of sheep with urine positive for
      leptospires on qPCR on each farm ranged from 11 to 88%. All but one of the qPCR
      positive animals were seropositive for serovar Hardjo. On two farms where Pomona
      exposure was observed, animals that were lost to follow-up had a higher geometric
      mean titre for serovar Pomona than those remaining in the study. CONCLUSIONS:
      This study demonstrated seasonal exposure from autumn to early summer in young
      sheep, a wide range of within-flock serological and shedding prevalence, and
      gives an estimation of the half-life of MAT titres in sheep. More extensive data
      are needed to fully understand the epidemiology of leptospirosis in sheep flocks
      across New Zealand and, along with economic analysis, to justify and design cost
      effective and efficient control measures to protect human and animal health.

PMID- 25966299
TI  - Lipid droplets formation in human endothelial cells in response to
      polyunsaturated fatty acids and 1-methyl-nicotinamide (MNA); confocal Raman
      imaging and fluorescence microscopy studies.
AB  - In this work the formation of lipid droplets (LDs) in human endothelial cells
      culture in response to the uptake of polyunsaturated fatty acids (PUFAs) was
      studied. Additionally, an effect of 1-methylnicotinamide (MNA) on the process of
      LDs formation was investigated. LDs have been previously described structurally
      and to some degree biochemically, however neither the precise function of LDs nor
      the factors responsible for LD induction have been clarified. Lipid droplets,
      sometimes referred in the literature as lipid bodies are organelles known to
      regulate neutrophil, eosinophil, or tumor cell functions but their presence and
      function in the endothelium is largely unexplored. 3D linear Raman spectroscopy
      was used to study LDs formation in vitro in a single endothelial cell. The method
      provides information about distribution and size of LDs as well as their
      composition. The incubation of endothelial cells with various PUFAs resulted in
      formation of LDs. As a complementary method for LDs identification a fluorescence
      microscopy was applied. Fluorescence measurements confirmed the Raman results
      suggesting endothelial cells uptake of PUFAs and subsequent LDs formation in the
      cytoplasm of the endothelium. Furthermore, MNA seem to potentiate intracellular
      uptake of PUFAs to the endothelium that may bear physiological and
      pharmacological significance. Confocal Raman imaging of HAoEC cell with LDs. 

PMID- 25966300
TI  - Interfacial Synthesis of Two-Dimensional Dendritic Platinum Nanoparticles Using
      Oleic Acid-in-Water Emulsion.
AB  - Here we propose facile and scalable synthesis of two-dimensional (2D) dendritic
      platinum nanoparticle at room temperature by exploiting an oil-in-water emulsion.
      The interfacial synthesis selectively provides platinum nanoparticle with 2D
      structure in high yield by controlling key reactants such as the amount of oleic
      acid and the concentration of block copolymer. Electrocatalytic activity of 2D
      dendritic platinum nanoparticle for oxygen reduction and methanol oxidation
      reaction is also examined. 

PMID- 25966301
TI  - Nanoconfinement induced crystal orientation and large piezoelectric coefficient
      in vertically aligned P(VDF-TrFE) nanotube array.
AB  - Vertically aligned piezoelectric P(VDF-TrFE) nanotube array comprising nanotubes
      embedded in anodized alumina membrane matrix without entanglement has been
      fabricated. It is found that the crystallographic polar axes of the P(VDF-TrFE)
      nanotubes are oriented along the nanotubes long axes. Such a desired crystal
      orientation is due to the kinetic selection mechanism for lamellae growth
      confined in the nanopores. The preferred crystal orientation in nanotubes leads
      to huge piezoelectric coefficients of the P(VDF-TrFE). The piezoelectric strain
      and voltage coefficients of P(VDF-TrFE) nanotube array are observed to be 1.97
      and 3.40 times of those for conventional spin coated film. Such a significant
      performance enhancement is attributed to the well-controlled polarization
      orientation, the elimination of the substrate constraint, and the low dielectric
      constant of the nanotube array. The P(VDF-TrFE) nanotube array exhibiting the
      unique structure and outstanding piezoelectric performance is promising for wide
      applications, including various electrical devices and electromechanical sensors
      and transducers. 

PMID- 25966302
TI  - Understanding the origin of phase segregation of nano-crystalline in a Be(x)Zn(1
      x)O random alloy: a novel phase of Be(1/3)Zn(2/3)O.
AB  - The usage of a BexZn1-xO alloy in ultraviolet (UV)-region optoelectronic devices
      is largely hindered by its intricate phase segregation of crystallites of
      different sizes. To understand the physical origin of this phase segregation
      phenomenon on the atomistic scale, we have undertaken an extensive study of the
      structural evolution of the segregation phases in the BexZn1-xO alloy at finite
      temperatures by using first-principles calculations combined with the cluster
      expansion approach. We find that a random alloy of BexZn1-xO tends to segregate
      into a mix-ordered phase below a critical temperature, by the growth of prototype
      and nano-sized structures. The segregated phases in BexZn1-xO entail not only ZnO
      or BeO crystallites, but also two as yet unreported phases with beryllium
      concentration of 1/3 and 2/3. Both new phases of BexZn1-xO are direct wide-gap
      semiconductors with band gap values of 4.88 eV and 6.78 eV respectively. We
      envisioned that the novel Be1/3Zn2/3O crystal is highly promising for solar-blind
      device applications. 

PMID- 25966303
TI  - Carbapenemase producing bacteria in the food supply escaping detection.
AB  - Carbapenem antimicrobials are critically important to human health and they are
      often the only remaining effective antibiotics for treating serious infections.
      Resistance to these drugs mediated by acquired carbapenemase enzymes is
      increasingly encountered in gram-negative bacteria and is considered a public
      health emergency. Animal origin food products are recognized as a potential
      source of resistant organisms, although carbapenem resistance has only recently
      been reported. In western countries there are active resistance surveillance
      programs targeting food animals and retail meat products. These programs
      primarily target beef, pork and poultry and focus exclusively on E. coli,
      Salmonella, Campylobacter spp. and Enterococcus spp. This global surveillance
      strategy does not capture the diversity of foods available nor does it address
      the presence of resistance gene-bearing mobile genetic elements in non-pathogenic
      bacterial taxa. To address this gap, a total of 121 seafood products originating
      in Asia purchased from retail groceries in Canada were tested. Samples were
      processed using a taxa-independent method for the selective isolation of
      carbapenem resistant organisms. Isolates were characterized by phenotypic
      antimicrobial susceptibility testing, PCR and DNA sequencing. Carbapenemase
      producing bacteria, all blaOXA-48, were isolated from 4 (3.3%) of the samples
      tested. Positive samples originated from China (n=2) and Korea (n=2) and included
      squid, sea squirt, clams and seafood medley. Carbapenemase producing organisms
      found include Pseudomonas, Stenotrophomonas and Myroides species. These findings
      suggest that non-pathogenic bacteria, excluded from resistance surveillance
      programs, in niche market meats may serve as a reservoir of carbapenemase genes
      in the food supply. 

PMID- 25966304
TI  - Millimeter Thin and Rubber-Like Solid-State Lighting Modules Fabricated Using
      Roll-to-Roll Fluidic Self-Assembly and Lamination.
AB  - A millimeter thin rubber-like solid-state lighting module is reported. The
      fabrication of the lighting module incorporates assembly and electrical
      connection of light-emitting diodes (LEDs). The assembly is achieved using a roll
      to-roll fluidic self-assembly. The LEDs are sandwiched in-between a stretchable
      top and bottom electrode to relieve the mechanical stress. The top contact is
      realized using a lamination technique that eliminates wire-bonding. 

PMID- 25966305
TI  - Outcomes of placing short implants in the posterior mandible: a preliminary
      randomized controlled trial.
AB  - BACKGROUND: Short dental implants can be an alternative to bone augmentation
      procedures at sites of reduced alveolar bone. Most studies on short implants are
      retrospective or multicentre reports that lack controlled and consistent
      comparison between different systems. This study aimed to compare clinical and
      radiographic outcomes of short implants in two different systems in the posterior
      mandible. METHODS: Twenty patients with two adjacent missing posterior teeth were
      recruited. Patients were assigned equally and randomly into two groups;
      Bicon((r)) (6 or 8 mm) and Ankylos((r)) (8 mm) implants. A two-stage surgical
      approach and single crowns were used for implant placement and loading. Outcomes
      included peri-implant clinical parameters, implant stability (Periotest values;
      PTVs) and peri-implant bone changes, which were assessed at baseline, 2, 6 and 12
      months post-loading. RESULTS: No implant loss was encountered up to 12 months
      post-loading. No significant difference in the clinical or radiographic
      parameters was observed except for PTVs (p < 0.05) that was lower in Ankylos((r))
      implants. CONCLUSIONS: The use of short dental implants was associated with
      excellent 12 months clinical and radiographic outcomes. Ankylos((r)) and
      Bicon((r)) implants demonstrated similar peri-implant soft tissue and alveolar
      bone changes. However, Ankylos((r)) implants demonstrated better implant
      stability at all evaluation intervals.

PMID- 25966307
TI  - Improved antibacterial phototoxicity of a neutral porphyrin in natural deep
      eutectic solvents.
AB  - Neutral porphyrins for antibacterial photodynamic therapy (aPDT) have received
      little attention due to their tendency to aggregate in aqueous media and reports
      of low phototoxic effect. These compounds may be less toxic to cells than
      positively and negatively charged photosensitisers. The preparation of highly
      bacterial phototoxic formulations of neutral porphyrins remains an open field of
      research with great potential if achievable. The purpose of this study was to
      develop novel hydrophilic formulations of the neutral porphyrin 5,10,15,20
      tetrakis(4-hydroxyphenyl)-porphyrin (THPP) by use of natural deep eutectic
      solvents (NADES) prepared by the solvent evaporation method. Physical and
      photochemical stability and in vitro photoinactivation of Enterococcus faecalis
      and Escherichia coli were investigated. Two of the 15 NADES investigated
      demonstrated superior solubilising properties of THPP. The photostability of THPP
      was higher in NADES than in methanol. A 100-fold dilution of the preparations
      with buffer to a final concentration of 0.5-5 nM THPP resulted in complete
      photoinactivation of E. faecalis and E. coli both in their exponential and
      stationary phase. THPP demonstrated significantly higher phototoxicity when
      formulated in NADES than in other aqueous preparations like phosphate buffered
      saline. NADES as a formulation concept for photosensitisers shows a great
      potential in aPDT.

PMID- 25966306
TI  - Mechanical properties of calvarial bones in a mouse model for craniosynostosis.
AB  - The mammalian cranial vault largely consists of five flat bones that are joined
      together along their edges by soft fibrous tissues called sutures. Premature
      closure of the cranial sutures, craniosynostosis, can lead to serious clinical
      pathology unless there is surgical intervention. Research into the genetic basis
      of the disease has led to the development of various animal models that display
      this condition, e.g. mutant type Fgfr2C342Y/+ mice which display early fusion of
      the coronal suture (joining the parietal and frontal bones). However, whether the
      biomechanical properties of the mutant and wild type bones are affected has not
      been investigated before. Therefore, nanoindentation was used to compare the
      elastic modulus of cranial bone and sutures in wild type (WT) and
      Fgfr2C342Y/+mutant type (MT) mice during their postnatal development. Further,
      the variations in properties with indentation position and plane were assessed.
      No difference was observed in the elastic modulus of parietal bone between the WT
      and MT mice at postnatal (P) day 10 and 20. However, the modulus of frontal bone
      in the MT group was lower than the WT group at both P10 (1.39+/-0.30 vs. 5.32+/
      0.68 GPa; p<0.05) and P20 (5.57+/-0.33 vs. 7.14+/-0.79 GPa; p<0.05). A wide range
      of values was measured along the coronal sutures for both the WT and MT samples,
      with no significant difference between the two groups. Findings of this study
      suggest that the inherent mechanical properties of the frontal bone in the mutant
      mice were different to the wild type mice from the same genetic background. These
      differences may reflect variations in the degree of biomechanical adaptation
      during skull growth, which could have implications for the surgical management of
      craniosynostosis patients. 

PMID- 25966309
TI  - Hair follicle melanocyte precursors are awoken by ultraviolet radiation via a
      cell extrinsic mechanism.
AB  - Melanocyte stem cells (MCSCs) in the upper portion of the hair follicle
      periodically supply melanocytes (MCs) that migrate downward into the hair bulb
      during anagen, the growth phase of the hair cycle. However MCs can also migrate
      upwards. We previously observed an increase in epidermal MC density in the mouse
      epidermis after a single ultraviolet radiation (UVR) exposure in neonatal, but
      not adult mice. To better understand MCSC activation by UVR we methodically
      studied the response of MCs to narrow band UVB (since UVA does not invoke this
      response) exposure in neonatal mice, and in adults at different stages of the
      hair cycle. We found that a single exposure of adult mice did not induce
      activation of MCSCs, in any stage of the hair cycle. When adult mice MCSCs were
      isolated in telogen, multiple UVB exposures resulted in their activation and
      production of daughter cells, which migrated upwards to the epidermis.
      Importantly, the MCSCs produced new progeny without themselves having incurred
      DNA damage after UVB exposure. This, together with examination of MC localisation
      in the skin of mice overexpressing stem cell factor in their keratinocytes, leads
      us to conclude that MCSC activation by UVB is driven via paracrine production of
      either SCF and/or other keratinocyte cytokines. We re-examined the increase in
      epidermal MC density in neonatal mouse skin. This effect was much more profound
      after only a single exposure than that of even multiple exposures to adult skin,
      and we show that in this setting also, the epidermal MCs mostly derive from
      activation of MC precursors in the upper hair follicle, and most likely via a
      cell extrinsic mechanism. Hence, although adaptive changes in the skin induced by
      repetitive UVB exposures are necessary in adult mice, in both the adult and
      neonatal context the division and migration upwards of follicular MCSCs is the
      major mode by which epidermal MC numbers increase after UVR exposure. 

PMID- 25966308
TI  - Ferrocene incorporated selenoureas as anticancer agents.
AB  - For a compound to be a best chemopreventive agent it should be a descent DNA
      binder and at the same time should be active against any of the three stages of
      carcinogenesis i.e. cancer initiation, cancer propagation and tumor growth. Most
      of the problems associated with chemotherapy can be overcome if the
      chemopreventive agent is active against all the three stages of cancer
      development. Cancer may be initiated by higher concentration of free radicals,
      inflammating agents and phase I enzymes (Cytochrome P450) in the body. Cancer
      propagation can be very efficiently controlled by inducing the phase II enzymes
      (glutathione S-transferases (GSTs), UDP-glucuronosyl transferases, and quinone
      reductases) in the body and cancer termination depends on the killing of the
      faulty cells i.e. cytotoxic actions. This article reports comprehensively the
      comparative DNA binding studies (with, cyclic voltammetry, UV-vis spectroscopy
      and viscometry), antioxidant activities (DPPH scavenging), anti-inflammatory
      activities (nitrite inhibition), phase I enzyme inhibition activities (aromatase
      inhibition), phase II enzyme induction studies (quinone reductase induction) and
      cytotoxic studies against neuroblastoma (MYCN2 and SK-N-SH), liver cancer (Hepa
      1c1c7) and breast cancer (MCF-7) of seventeen ferrocene incorporated selenoureas.

PMID- 25966310
TI  - Host-pathogen interaction during bacterial vaccination.
AB  - Vaccines have been developed and deployed against several important bacterial
      pathogens of humans, including Neisseria meningitidis, Bordetella pertussis,
      Streptococcus pneumoniae and Mycobacterium tuberculosis. These vaccines are
      generally considered a successful public health measure and are effective at
      controlling disease symptoms and/or burden. However, a troubling consequence of
      recent vaccination programs has been the selection of vaccine escape mutants,
      whereby the pathogen displays a different repertoire of immune targets than those
      represented in the vaccine formulation. To address these issues of antigenic
      variation and bacterial evolution, continued and sustained efforts in
      epidemiological surveillance, vaccine development/formulation research, and
      understanding of the host-pathogen interaction are required. 

PMID- 25966311
TI  - Nomenclature updates resulting from the evolution of avian influenza A(H5) virus
      clades 2.1.3.2a, 2.2.1, and 2.3.4 during 2013-2014.
AB  - AIM: The A/goose/Guangdong/1/96-like hemagglutinin (HA) genes of highly
      pathogenic avian influenza (HPAI) A(H5) viruses have continued to rapidly evolve
      since the most recent update to the H5 clade nomenclature by the WHO/OIE/FAO H5N1
      Evolution Working Group. New clades diverging beyond established boundaries need
      to be identified and designated accordingly. METHOD: Hemagglutinin sequences
      deposited in publicly accessible databases up to December 31, 2014, were analyzed
      by phylogenetic and average pairwise distance methods to identify new clades that
      merit nomenclature changes. RESULTS: Three new clade designations were
      recommended based on division of clade 2.1.3.2a (Indonesia), 2.2.1 (Egypt), and
      2.3.4 (widespread detection in Asia, Europe, and North America) that includes
      newly emergent HPAI virus subtypes H5N2, H5N3, H5N5, H5N6, and H5N8. CONCLUSION:
      Continued global surveillance for HPAI A(H5) viruses in all host species and
      timely reporting of sequence data will be critical to quickly identify new clades
      and assess their potential impact on human and animal health.

PMID- 25966312
TI  - Sesquiterpenes from the roots of Illicium oligandrum.
AB  - Two new sesquiterpenes, oligandrin (1) and oligandric acid (2), together with
      three analogues, tashironin A (3), tashironin (4), and oplodiol (5), were
      isolated from the roots of Illicium oligandrum. The structures of new compounds
      were determined based on 1D and 2D NMR experiments and X-ray diffraction.
      Compound 1 represents a presumed biosynthetic precursor of seco-prezizaane
      sesquiterpenes which consists of a novel 6/6/5 tricarbocyclic skeleton. Compound
      2 is the first example of chamipinene-type sesquiterpene possessing a 6/4/6
      tricyclic system from the genus Illicium. Compounds 1-5 were evaluated in vitro
      for their activity against coxsackie virus B3 (CVB3), influenza virus
      A/Hanfang/359/95 (H3N2), and influenza virus A/FM/1/47 (H1N1). Compound 1 showed
      selective antiviral activity against CVB3 with IC50 value of 11.11 MUM. 

PMID- 25966313
TI  - Arene oxidation with malonoyl peroxides.
AB  - Malonoyl peroxide 7, prepared in a single step from the commercially available
      diacid, is an effective reagent for the oxidation of aromatics. Reaction of an
      arene with peroxide 7 at room temperature leads to the corresponding protected
      phenol which can be unmasked by aminolysis. An ionic mechanism consistent with
      the experimental findings and supported by isotopic labeling, Hammett analysis,
      EPR investigations, and reactivity profile studies is proposed. 

PMID- 25966315
TI  - Epigenetics and pharmacology.
AB  - Recent advances in the understanding of gene regulation have shown there to be
      much more regulation of the genome than first thought, through epigenetic
      mechanisms. These epigenetic mechanisms are systems that have evolved to either
      switch off gene activity altogether, or fine-tune any existing genetic
      activation. Such systems are present in all genes and include chromatin
      modifications and remodelling, DNA methylation (such as CpG island methylation
      rates) and histone covalent modifications (e.g. acetylation, methylation), RNA
      interference by short interfering RNAs (siRNAs) and long non-coding RNAs
      (ncRNAs). These systems regulate genomic activity 'beyond' simple transcriptional
      factor inducer or repressor function of genes to generate mRNA. Epigenetic
      regulation of gene activity has been shown to be important in maintaining normal
      phenotypic activity of cells, as well as having a role in development and
      diseases such as cancer and neurodegenerative disorders such as Alzheimer's.
      Newer classes of drugs regulate epigenetic mechanisms to counteract disease
      states in humans. The reports in this issue describe some advances in epigenetic
      understanding that relate to human disease, and our ability to control these
      mechanisms by pharmacological means. Increasingly the importance of epigenetics
      is being uncovered - it is pharmacology that will have to keep pace.

PMID- 25966316
TI  - Anchoring vignettes in the Health and Retirement Study: how do medical
      professionals and disability recipients characterize the severity of work
      limitations?
AB  - PURPOSE: Recent studies report systematic differences in how individuals
      categorize the severity of identical health and work limitation vignettes. We
      investigate how health professionals and disability recipients characterize the
      severity of work limitations and whether their reporting patterns are robust to
      demographic, education, and health characteristics. We use the results to
      illustrate the potential impact of reporting heterogeneity on the distribution of
      work disability estimated from self-reported categorical health and disability
      data. METHOD: Nationally representative data on anchoring disability vignettes
      from the 2004 Health and Retirement Study (HRS) are used to investigate how
      respondents with an occupation background in health and Social Security
      disability beneficiaries categorize work limitation vignettes. Using pain,
      cardiovascular health, and depression vignettes, we estimate generalized ordered
      probit models (N = 2,660 individuals or 39,681 person-vignette observations) that
      allow the severity thresholds to vary by respondent characteristics. RESULTS: We
      find that health professionals (excluding nurses) and disability recipients tend
      to classify identical work limitations as more severe compared to non-health
      professional non-disabled respondents. For disability recipients, the differences
      are most pronounced and particularly visible in the tails of the work limitations
      distribution. For health professionals, we observe smaller differences, affecting
      primarily the classification of mildly and moderately severe work limitations.
      The patterns for health professionals (excluding nurses) are robust to
      demographics, education, and health conditions. The greater likelihood of viewing
      the vignette person as more severely work limited observed among disability
      recipients is mostly explained by the fact that these respondents also tend to be
      in poorer health which itself predicts a more inclusive scale. CONCLUSIONS:
      Knowledge of reporting scales from health professionals and disabled individuals
      can benefit researchers in a broad range of applications in health and disability
      research. They may be useful as reference scales to evaluate disability survey
      data. Such knowledge may be beneficial when studying disability programs. Given
      the increasing availability of anchoring vignette data in surveys, this is a
      promising area for future evaluation research.

PMID- 25966318
TI  - Quasi-polaritons in Bose-Einstein condensates induced by Casimir-Polder
      interaction with graphene.
AB  - We consider the mechanical coupling between a two-dimensional Bose-Einstein
      condensate and a graphene sheet via the vacuum fluctuations of the
      electromagnetic field which are at the origin of the so-called Casimir-Polder
      potential. By deriving a self-consistent set of equations governing the dynamics
      of the condensate and the flexural (out-of-plane) modes of the graphene, we can
      show the formation of a new type of purely acoustic quasi-particle excitation, a
      quasi-polariton resulting from the coherent superposition of quanta of flexural
      and Bogoliubov modes. 

PMID- 25966317
TI  - Effects of multidisciplinary team care on the survival of patients with different
      stages of non-small cell lung cancer: a national cohort study.
AB  - In Taiwan, cancer is the top cause of death, and the mortality rate of lung
      cancer is the highest of all cancers. Some studies have demonstrated that
      multidisciplinary team (MDT) care can improve survival rates of non-small cell
      lung cancer (NSCLC) patients. However, no study has discussed the effect of MDT
      care on different stages of NSCLC. The target population for this study consisted
      of patients with NSCLC newly diagnosed in the 2005-2010 Cancer Registry. The data
      was linked with the 2002-2011 National Health Insurance Research Database and the
      2005-2011 Cause of Death Statistics Database. The multivariate Cox proportional
      hazards model was used to explore whether the involvement of MDT care had an
      effect on survival. This study applied the propensity score as a control variable
      to reduce selection bias between patients with and without involvement of MDT
      care. The adjusted hazard ratio (HR) of death of MDT participants with stage III
      & IV NSCLC was significantly lower than that of MDT non-participants (adjusted HR
      = 0.87, 95% confidence interval = 0.84-0.90). This study revealed that MDT care
      are significantly associated with higher survival rate of patients with stage III
      and IV NSCLC, and thus MDT care should be used in the treatment of these
      patients. 

PMID- 25966319
TI  - DNA Binding to the Silica Surface.
AB  - We investigate the DNA-silica binding mechanism using molecular dynamics
      simulations. This system is of technological importance, and also of interest to
      explore how negatively charged DNA can bind to a silica surface, which is also
      negatively charged at pH values above its isoelectric point near pH 3. We find
      that the two major binding mechanisms are attractive interactions between DNA
      phosphate and surface silanol groups and hydrophobic bonding between DNA base and
      silica hydrophobic region. Umbrella sampling and the weighted histogram analysis
      method (WHAM) are used to calculate the free energy surface for detachment of DNA
      from a binding configuration to a location far from the silica surface. Several
      factors explain why single-stranded DNA (ssDNA) has been observed to be more
      strongly attracted to silica than double-stranded (dsDNA): (1) ssDNA is more
      flexible and therefore able to maximize the number of binding interactions. (2)
      ssDNA has free unpaired bases to form hydrophobic attachment to silica while
      dsDNA has to break hydrogen bonds with base partners to get free bases. (3) The
      linear charge density of dsDNA is twice that of ssDNA. We devise a procedure to
      approximate the atomic forces between biomolecules and amorphous silica to enable
      large-scale biomolecule-silica simulations as reported here. 

PMID- 25966320
TI  - Laser Transfer of Metals and Metal Alloys for Digital Microfabrication of 3D
      Objects.
AB  - 3D copper logos printed on epoxy glass laminates are demonstrated. The structures
      are printed using laser transfer of molten metal microdroplets. The example in
      the image shows letters of 50 um width, with each letter being taller than the
      last, from a height of 40 um ('s') to 190 um ('l'). The scanning microscopy image
      is taken at a tilt, and the topographic image was taken using interferometric 3D
      microscopy, to show the effective control of this technique. 

PMID- 25966322
TI  - Cumulative therapeutic effects of phytochemicals in Arnica montana flower extract
      alleviated collagen-induced arthritis: inhibition of both pro-inflammatory
      mediators and oxidative stress.
AB  - BACKGROUND: The plant Arnica montana is used in folk medicine to alleviate pain,
      inflammation and swelling of muscles and joints associated with rheumatoid
      arthritis and other inflammatory conditions. The present study aimed to
      investigate the therapeutic effects and mechanism of action of A. montana flower
      methanol extract (AMME) against both inflammation and oxidative stress in a
      collagen-induced arthritis (CIA) rat model. RESULTS: Oral administration of AMME
      was found to reduce clinical signs and improve the histological and radiological
      status of the hind limb joints. AMME-treated rats had lower expression levels of
      nitric oxide, tumor necrosis factor-alpha, interleukins (IL-1beta, IL-6 and IL
      12) and titer of anti-type II collagen antibody compared with untreated CIA rats.
      Furthermore, by inhibiting these mediators, AMME also contributed towards the
      reversal of disturbed antioxidant levels and peroxidative damage. CONCLUSION: The
      alleviation of arthritis in rats was very likely due to the combined action of
      phenolic and flavonoid compounds, the major constituents identified by gas
      chromatography/mass spectrometry (GC/MS) analysis. The study also shed some light
      on mechanisms involved in diminution of inflammatory mediators and free radical
      generating toxicants and enhancement of the antioxidant armory, thereby
      preventing further tissue damage, injury and synovial hyperproliferation in
      arthritis.

PMID- 25966324
TI  - Compositional assessments of key maize populations: B73 hybrids of the Nested
      Association Mapping founder lines and diverse landrace inbred lines.
AB  - The present study provides an assessment of the compositional diversity in maize
      B73 hybrids derived both from the Nested Association Mapping (NAM) founder lines
      and from a diverse collection of landrace accessions from North and South
      America. The NAM founders represent a key population of publicly available lines
      that are used extensively in the maize community to investigate the genetic basis
      of complex traits. Landraces are also of interest to the maize community as they
      offer the potential to discover new alleles that could be incorporated into
      modern maize lines. The compositional analysis of B73 hybrids from the 25 NAM
      founders and 24 inbred lines derived from landraces included measurements of
      proximates (protein, fat, ash, and starch), fibers, minerals, amino acids, fatty
      acids, tocopherols (alpha-, gamma-, and delta-), beta-carotene, phytic acid, and
      raffinose. Grain was harvested from a replicated trial in New York, USA. For each
      data set (NAM and landrace) canonical discriminant analysis allowed separation of
      distinct breeding groups (tropical, temperate, flint, mixed/intermediate) within
      each data set. Overall, results highlighted extensive variation in all
      composition components assessed for both sets of hybrids. The variation observed
      for some components within the landraces may therefore be of value for increasing
      their levels in modern maize lines. The study described here provided significant
      information on contributions of conventional breeding to crop compositional
      variation, as well as valuable information on key genetic resources for the maize
      community in the development of new improved lines. 

PMID- 25966325
TI  - Catalytic amidation of unactivated ester derivatives mediated by
      trifluoroethanol.
AB  - A catalytic amidation method has been developed, employing 2,2,2-trifluoroethanol
      to facilitate condensation of unactivated esters and amines, enabling the
      synthesis of a range of amide products in good to excellent yields. Mechanistic
      studies indicate the reaction proceeds through a trifluoroethanol-derived active
      ester intermediate. 

PMID- 25966323
TI  - Evolution of functional six-nucleotide DNA.
AB  - Axiomatically, the density of information stored in DNA, with just four
      nucleotides (GACT), is higher than in a binary code, but less than it might be if
      synthetic biologists succeed in adding independently replicating nucleotides to
      genetic systems. Such addition could also add functional groups not found in
      natural DNA, but useful for molecular performance. Here, we consider two new
      nucleotides (Z and P, 6-amino-5-nitro-3-(1'-beta-D-2'-deoxyribo-furanosyl)-2(1H)
      pyridone and 2-amino-8-(1'-beta-D-2'-deoxyribofuranosyl)-imidazo[1,2-a]-1,3,5
      triazin-4(8H)-one). These are designed to pair via complete Watson-Crick
      geometry. These were added to a library of oligonucleotides used in a laboratory
      in vitro evolution (LIVE) experiment; the GACTZP library was challenged to
      deliver molecules that bind selectively to liver cancer cells, but not to
      untransformed liver cells. Unlike in classical in vitro selection, low levels of
      mutation allow this system to evolve to create binding molecules not necessarily
      present in the original library. Over a dozen binding species were recovered. The
      best had Z and/or P in their sequences. Several had multiple, nearby, and
      adjacent Zs and Ps. Only the weaker binders contained no Z or P at all. This
      suggests that this system explored much of the sequence space available to this
      genetic system and that GACTZP libraries are richer reservoirs of functionality
      than standard libraries.

PMID- 25966326
TI  - Red cell volume distribution width-to-platelet ratio in assessment of liver
      fibrosis in patients with chronic hepatitis B.
AB  - BACKGROUND & AIMS: Precise assessment of liver fibrosis is necessary in patients
      with chronic liver disease. We investigated the performance of red cell volume
      distribution width-to-platelet ratio for the assessment of liver fibrosis in
      patients with chronic hepatitis B. METHODS: A total of 482 consecutive patients
      with chronic hepatitis B who underwent liver biopsy between October 2005 and May
      2014 were recruited. Liver stiffness was measured using transient elastography.
      FIB-4 score, red cell volume distribution width-to-platelet ratio and the
      aspartate aminotransferase-to-platelet ratio index were also assessed. RESULTS: A
      total of 271 (56.2%) patients were males. The median age was 44 years. F1, F2, F3
      and F4 fibrosis stages were identified in 68 (14.1%), 137 (28.4%), 64 (13.3%) and
      213 (44.2%) of the patients respectively. The mean red cell volume distribution
      width-to-platelet ratio increased with liver fibrosis severity: F1, 0.065; F2,
      0.077; F3, 0.097 and F4, 0.121 (P < 0.01). The area under the receiver operating
      characteristic curve of the red cell volume distribution width-to-platelet ratio
      for predicting significant fibrosis (>=F2) was 0.747. This result was inferior to
      transient elastography (0.866, P = 0.004), but comparable to FIB-4 (0.782, P =
      0.427) and aspartate aminotransferase-to-platelet ratio index (0.716, P = 0.507).
      The area under the receiver operating characteristic curve of red cell volume
      distribution width-to-platelet ratio for predicting cirrhosis (F4) was 0.811,
      which was inferior to liver stiffness (0.915, P < 0.001), but comparable to FIB-4
      (0.804, P = 0.805) and superior to aspartate aminotransferase-to-platelet ratio
      index (0.680, P < 0.001). CONCLUSIONS: The accuracy of red cell volume
      distribution width-to-platelet ratio was acceptable for the assessment of liver
      fibrosis in patients with chronic hepatitis B. When transient elastography is not
      available, red cell volume distribution width-to-platelet ratio assessment is a
      simple method that can be used to reduce the need for liver biopsy.

PMID- 25966327
TI  - Assessment of ferrous chloride and Portland cement for the remediation of
      chromite ore processing residue.
AB  - Chromite Ore Processing Residue (COPR) is an industrial waste containing up to 7%
      chromium (Cr) including up to 5% hexavalent chromium [Cr(VI)]. The remediation of
      COPR has been challenging due to the slow release of Cr(VI) from a clinker like
      material and thereby the incomplete detoxification of Cr(VI) by chemical
      reagents. The use of sulfur based reagents such as ferrous sulfate and calcium
      polysulfide to detoxify Cr(VI) has exasperated the swell potential of COPR upon
      treatment. This study investigated the use of ferrous chloride alone and in
      combination with Portland cement to address the detoxification of Cr(VI) in COPR
      and the potential swell of COPR. Chromium regulatory tests, X-ray powder
      diffraction (XRPD) analyses and X-ray absorption near edge structure (XANES)
      analyses were used to assess the treatment results. The treatment results
      indicated that Cr(VI) concentrations for the acid pretreated micronized COPR as
      measured by XANES analyses were below the New Jersey Department of Environmental
      Protection (NJDEP) standard of 20 mg kg(-1). The Toxicity characteristic leaching
      procedure (TCLP) Cr concentrations for all acid pretreated samples also were
      reduced below the TCLP regulatory limit of 5 mg L(-1). Moreover, the TCLP Cr
      concentration for the acid pretreated COPR with particle size ?0.010 mm were less
      than the universal treatment standard (UTS) of 0.6 mg L(-1). The treatment
      appears to have destabilized all COPR potential swell causing minerals. The
      unconfined compressive strength (UCS) for the treated samples increased
      significantly upon treatment with Portland cement.

PMID- 25966328
TI  - Simultaneous removal of tetracycline hydrochloride and As(III) using poorly
      crystalline manganese dioxide.
AB  - Simultaneous removal of antibiotic tetracycline hydrochloride (TC) and As(III) by
      poorly-crystalline Mn dioxide was investigated. TC and As(III) can be effectively
      oxidized and removed by MnO2. High concentrations of TC and As(III) competed with
      each other for oxidation or adsorption sites on MnO2 and thus affected their
      removal efficiency. The intermediates and products of TC after reaction with
      poorly-crystalline manganese dioxide were identified by LC-ESI-MS (liquid
      chromatography-electrospray ionization-mass spectrometry), and the decomposition
      pathways of TC by MnO2 were proposed. This study is helpful for understanding the
      importance of environmental Mn dioxides in the decontamination of combined
      pollution by organic pollutants and metal(loid)s. 

PMID- 25966329
TI  - Effective remediation of phenol,2,4-bis(1,1-dimethylethyl) and bis(2-ethylhexyl)
      phthalate in farm effluent using Guar gum--A plant based biopolymer.
AB  - This study was carried out to evaluate the efficiency of Guar gum in removing
      Persistent Organic Pollutants (POPs), viz. phenol,2,4-bis(1,1-dimethylethyl) and
      bis(2-ethylhexyl) phthalate (DEHP), from farm effluent. The removal efficiency
      was compared with alum. The results indicated that 4.0 mg L(-1) of Guar gum at pH
      7 could remove 99.70% and 99.99% of phenol,2,4-bis(1,1-dimethylethyl) and DEHP,
      respectively. Box Behnken design was used for optimization of the operating
      parameters for optimal POPs removal. Scanning Electron Microscopy (SEM) and
      Fourier Transform Infrared (FTIR) spectroscopy studies were conducted on the
      flocs. SEM micrographs showed numerous void spaces in the flocs produced by Guar
      gum as opposed to those produced by alum. This indicated why Guar gum was more
      effective in capturing and removal of suspended particles and POPs as compared to
      alum. FTIR spectra indicated a shift in the bonding of functional groups in the
      flocs produced by Guar gum as compared to raw Guar gum powder signifying chemical
      attachment of the organics present in the effluent to the coagulant resulting in
      their removal. Guar gum is highly recommended as a substitute to chemical
      coagulant in treating POPs due to its non-toxic and biodegradable
      characteristics.

PMID- 25966330
TI  - Effects of water matrix on virus inactivation using common virucidal techniques
      for condensate urine disinfection.
AB  - Three common virucidal techniques (chlorine, UV and UV/TiO2) were applied to
      inactivate virus (MS2 and Phi X174) in condensate water after the evaporation of
      source-separated urine for reclaimed water. The inactivation efficiencies were
      compared with the results of previous studies, with the emphasis on the analysis
      of water matrix effects. Results showed that all virus inactivation in condensate
      water were lower than the control (in sterilized DI water). As for UV/TiO2
      disinfection, both nitrate and ammonia nitrogen could promote slightly viral
      inactivation, while the inhibition by urea was dominant. Similarly, ammonia
      nitrogen had greater impacts on chlorine disinfection than urea and nitrate. In
      contrast, all water matrices (urea, nitrate and ammonia nitrogen) had little
      influence on UV disinfection. Based on the findings in this study, UV
      disinfection could be recommended for disinfecting the reclaimed water from the
      evaporation of source-separated urine. 

PMID- 25966331
TI  - The role of forward osmosis and microfiltration in an integrated osmotic
      microfiltration membrane bioreactor system.
AB  - This study investigates the performance of an integrated osmotic and
      microfiltration membrane bioreactor (O/MF-MBR) system for wastewater treatment
      and reclamation. The O/MF-MBR system simultaneously used microfiltration (MF) and
      forward osmosis (FO) membranes to extract water from the mixed liquor of an
      aerobic bioreactor. The MF membrane facilitated the bleeding of dissolved
      inorganic salts and thus prevented the build-up of salinity in the bioreactor. As
      a result, sludge production and microbial activity were relatively stable over 60
      days of operation. Compared to MF, the FO process produced a better permeate
      quality in terms of nutrients, total organic carbon, as well as hydrophilic and
      biologically persistent trace organic chemicals (TrOCs). The high rejection by
      the FO membrane also led to accumulation of hydrophilic and biologically
      persistent TrOCs in the bioreactor, consequently increasing their concentration
      in the MF permeate. On the other hand, hydrophobic and readily biodegradable
      TrOCs were minimally detected in both MF and FO permeates, with no clear
      difference in the removal efficiencies between two processes.

PMID- 25966332
TI  - Pilot study of massage in veterans with knee osteoarthritis.
AB  - OBJECTIVES: To (1) assess the feasibility and acceptability of Swedish massage
      among Department of Veterans Affairs (VA) health care users with knee
      osteoarthritis (OA) and (2) collect preliminary data on efficacy of Swedish
      massage in this patient group. DESIGN: Experimental pilot study. SETTING: Duke
      Integrative Medicine clinic and VA Medical Center, Durham, North Carolina.
      PATIENTS: Twenty-five veterans with symptomatic knee OA. INTERVENTIONS: Eight
      weekly 1-hour sessions of full-body Swedish massage. OUTCOME MEASURES: Primary:
      Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and global
      pain (Visual Analog Scale [VAS]). Secondary: National Institutes of Health
      Patient Reported Outcomes Measurement Information System-Pain Interference
      Questionnaire 6b (PROMIS-PI 6b), 12-Item Short-Form Health Survey (SF-12 v1) and
      the EuroQol health status index (EQ-5D-5L), knee range of motion (ROM), and time
      to walk 50 feet. RESULTS: Study feasibility was established by a 92% retention
      rate with 99% of massage visits and 100% of research visits completed. Results
      showed significant improvements in self-reported OA-related pain, stiffness and
      function (30% improvement in Global WOMAC scores; p=0.001) and knee pain over the
      past 7 days (36% improvement in VAS score; p<0.001). PROMIS-PI, EQ-5D-5L, and
      physical composite score of the SF-12 also significantly improved (p<0.01 for
      all), while the mental composite score of the SF-12 and knee ROM showed trends
      toward significant improvement. Time to walk 50 feet did not significantly
      improve. CONCLUSIONS: Results of this pilot study support the feasibility and
      acceptability of Swedish massage among VA health care users as well as
      preliminary data suggesting its efficacy for reducing pain due to knee OA. If
      results are confirmed in a larger randomized trial, massage could be an important
      component of regular care for these patients.

PMID- 25966333
TI  - Toxic and genotoxic effects of the imazethapyr-based herbicide formulation Pivot
      H(r) on montevideo tree frog Hypsiboas pulchellus tadpoles (Anura, Hylidae).
AB  - Acute lethal and sublethal toxicity of the imidazolinone imazethapyr (IMZT)-based
      commercial formulation herbicide Pivot H(r) (10.59% IMZT) was evaluated on
      Hypsiboas pulchellus tadpoles. Whereas mortality was used as the end point for
      lethality, frequency of micronuclei (MNs) and other nuclear abnormalities as well
      as DNA single-strand breaks evaluated by the single cell gel electrophoresis
      assay were employed to test genotoxicity. Behavioral, growth, developmental, and
      morphological abnormalities were also employed as sublethal end points. Mortality
      studies revealed equivalent LC50 (96h) values of 1.49mg/L (confidence limit, 1.09
      1.63) and 1.55mg/L (confidence limit, 1.51-1.60) IMZT for Gosner stage (GS) 25
      and GS36, respectively. Behavioral changes, i.e., irregular swimming and
      immobility, as well as a decreased frequency of keratodonts were observed. The
      herbicide increased the frequency of MNs in circulating erythrocytes of tadpoles
      exposed for 48h to the highest concentration assayed (1.17mg/L). However,
      regardless of the concentration of the herbicide assayed, an enhanced frequency
      of MNs was observed in tadpoles exposed for 96h. The herbicide was able to induce
      other nuclear abnormalities, i.e., blebbed and notched nuclei, only when tadpoles
      were exposed for 96h. In addition, we observed that exposure to IMZT within the
      0.39-1.17mg/L range increased the genetic damage index in treatments lasting for
      both 48 and 96h. This study represents the first evidence of acute lethal and
      sublethal effects exerted by IMZT on amphibians. Finally, our findings highlight
      the properties of this herbicide that jeopardize nontarget living species exposed
      to IMZT. 

PMID- 25966334
TI  - Nitric oxide contributes to minerals absorption, proton pumps and hormone
      equilibrium under cadmium excess in Trifolium repens L. plants.
AB  - Nitric oxide (NO) is a stress-signaling molecule in plants that mediates a wide
      range of physiological processes and responses to metal toxicity. In this work,
      various NO modulators (NO donor: SNP; NO scavenger: cPTIO; NO synthase inhibitor:
      l-NAME; and SNP analogs: sodium nitrite/nitrate and sodium ferrocyanide) were
      investigated to determine the role of NO in Trifolium repens L. plants exposed to
      Cd. Cd (100MUM) markedly reduced biomass, NO production and chlorophyll (Chl a,
      Chl b and total Chl) concentration but stimulated reactive oxygen species (ROS)
      and Cd accumulation in plants. SNP (50MUM) substantially attenuated growth
      inhibition, reduced hydrogen peroxide (H2O2) and malonyldialdehyde (MDA) levels,
      stimulated ROS-scavenging enzymes/agents, and mitigated the H(+)-ATPase
      inhibition in proton pumps. Interestingly, SNP considerably up-regulated the
      levels of jasmonic acid (JA) and proline in plant tissues but down-regulated the
      levels of ethylene (ET) in both shoots and roots and the level of salicylic acid
      (SA) in roots only, which might be related to the elevated NO synthesis.
      Additionally, SNP (25-200MUM) regulated mineral absorption and, particularly at
      50MUM, significantly enhanced the uptake of shoot magnesium (Mg) and copper (Cu)
      and of root calcium (Ca), Mg and iron (Fe). Nevertheless, the effects of SNP on
      plant growth were reversed by cPTIO and l-NAME, suggesting that the protective
      effect of SNP might be associated with NO synthesis in vivo. Moreover, SNP
      analogs did not display roles similar to that of SNP. These results indicated
      that NO depleted Cd toxicity by eliminating oxidative damage, enhancing minerals
      absorption, regulating proton pumps, and maintaining hormone equilibrium. 

PMID- 25966335
TI  - Optimization and modelling of synthetic azo dye wastewater treatment using
      Graphene oxide nanoplatelets: Characterization toxicity evaluation and
      optimization using Artificial Neural Network.
AB  - Azo dyes pose a major threat to current civilization by appearing in almost all
      streams of wastewater. The present investigation was carried out to examine the
      potential of Graphene oxide (GO) nanoplatelets as an efficient, cost-effective
      and non-toxic azo dye adsorbent for efficient wastewater treatment. The treatment
      process was optimized using Artificial Neural Network for maximum percentage dye
      removal and evaluated in terms of varying operational parameters, process
      kinetics and thermodynamics. A brief toxicity assay was also designed using fresh
      water snail Bellamya benghalensis to analyze the quality of the treated solution.
      97.78% removal of safranin dye was obtained using GO as adsorbent.
      Characterization of GO nanoplatelets (using SEM, TEM, AFM and FTIR) reported the
      changes in its structure as well as surface morphology before and after use and
      explained its prospective as a good and environmentally benign adsorbent in very
      low quantities. The data recorded when subjected to different isotherms best
      fitted the Temkin isotherm. Further analysis revealed the process to be
      endothermic and chemisorption in nature. The verdict of the toxicity assay
      rendered the treated permeate as biologically safe for discharge or reuse in
      industrial and domestic purposes. 

PMID- 25966336
TI  - Psychological therapies for sickle cell disease and pain.
AB  - BACKGROUND: Sickle cell disease comprises a group of genetic blood disorders. It
      occurs when the sickle haemoglobin gene is inherited from both parents. The
      effects of the condition are: varying degrees of anaemia which, if severe, can
      reduce mobility; a tendency for small blood capillaries to become blocked causing
      pain in muscle and bone commonly known as 'crises'; damage to major organs such
      as the spleen, liver, kidneys, and lungs; and increased vulnerability to severe
      infections. There are both medical and non-medical complications, and treatment
      is usually symptomatic and palliative in nature. Psychological interventions for
      individuals with sickle cell disease might complement current medical treatment,
      and studies of their efficacy have yielded encouraging results. This is an update
      of a previously published Cochrane Review. OBJECTIVES: To examine the evidence
      that psychological interventions improve the ability of people with sickle cell
      disease to cope with their condition. SEARCH METHODS: We searched the Cochrane
      Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register,
      which comprises references identified from comprehensive electronic database
      searches and the Internet, handsearches of relevant journals and abstract books
      of conference proceedings.Date of the most recent search of the Group's
      Haemoglobinopathies Trials Register: 17 February 2015. SELECTION CRITERIA: All
      randomised or quasi-randomised controlled trials comparing psychological
      interventions with no (psychological) intervention in people with sickle cell
      disease. DATA COLLECTION AND ANALYSIS: Both authors independently extracted data
      and assessed the risk of bias of the included studies. MAIN RESULTS: Twelve
      studies were identified in the searches and seven of these were eligible for
      inclusion in the review. Five studies, involving 260 participants, provided data
      for analysis. One study showed that cognitive behaviour therapy significantly
      reduced the affective component of pain (feelings about pain), mean difference 
      0.99 (95% confidence interval -1.62 to -0.36), but not the sensory component
      (pain intensity), mean difference 0.00 (95% confidence interval -9.39 to 9.39).
      One study of family psycho-education was not associated with a reduction in
      depression. Another study evaluating cognitive behavioural therapy had
      inconclusive results for the assessment of coping strategies, and showed no
      difference between groups assessed on health service utilisation. In addition,
      family home-based cognitive behavioural therapy did not show any difference
      compared to disease education. One study of patient education on health beliefs
      showed a significant improvement in attitudes towards health workers, mean
      difference -4.39 (95% CI -6.45 to -2.33) and medication, mean difference -1.74
      (95% CI -2.98 to -0.50). Nonetheless, these results may not apply across all
      ages, severity of sickle cell disease, types of pain (acute or chronic), or
      setting. AUTHORS' CONCLUSIONS: Evidence for the efficacy of psychological
      therapies in sickle cell disease is currently limited. This systematic review has
      clearly identified the need for well-designed, adequately-powered, multicentre
      randomised controlled trials assessing the effectiveness of specific
      interventions in sickle cell disease.

PMID- 25966337
TI  - Pharmaceutical policies: effects of cap and co-payment on rational use of
      medicines.
AB  - BACKGROUND: Growing expenditures on prescription medicines represent a major
      challenge to many health systems. Cap and co-payment policies are intended as an
      incentive to deter unnecessary or marginal utilisation, and to reduce third-party
      payer expenditures by shifting parts of the financial burden from insurers to
      patients, thus increasing their financial responsibility for prescription
      medicines. Direct patient payment policies include caps (maximum numbers of
      prescriptions or medicines that are reimbursed), fixed co-payments (patients pay
      a fixed amount per prescription or medicine), co-insurance (patients pay a
      percentage of the price), ceilings (patients pay the full price or part of the
      cost up to a ceiling, after which medicines are free or are available at reduced
      cost) and tier co-payments (differential co-payments usually assigned to generic
      and brand medicines). This is the first update of the original review.
      OBJECTIVES: To determine the effects of cap and co-payment (cost-sharing)
      policies on use of medicines, healthcare utilisation, health outcomes and costs
      (expenditures). SEARCH METHODS: For this update, we searched the following
      databases and websites: The Cochrane Central Register of Controlled Trials
      (CENTRAL) (including the Cochrane Effective Practice and Organisation of Care
      (EPOC) Group Specialised Register, Cochrane Library; MEDLINE, Ovid; EMBASE, Ovid;
      IPSA, EBSCO; EconLit, ProQuest; Worldwide Political Science Abstracts, ProQuest;
      PAIS International, ProQuest; INRUD Bibliography; WHOLIS, WHO; LILACS), VHL;
      Global Health Library WHO; PubMed, NHL; SCOPUS; SciELO, BIREME; OpenGrey; JOLIS
      Library Network; OECD Library; World Bank e-Library; World Health Organization,
      WHO; World Bank Documents & Reports; International Clinical Trials Registry
      Platform (ICTRP), WHO; ClinicalTrials.gov, NIH. We searched all databases during
      January and February 2013, apart from SciELO, which we searched in January 2012,
      and ICTRP and ClinicalTrials.gov, which we searched in March 2014. SELECTION
      CRITERIA: We defined policies in this review as laws, rules or financial or
      administrative orders made by governments, non-government organisations or
      private insurers. We included randomised controlled trials, non-randomised
      controlled trials, interrupted time series studies, repeated measures studies and
      controlled before-after studies of cap or co-payment policies for a large
      jurisdiction or system of care. To be included, a study had to include an
      objective measure of at least one of the following outcomes: medicine use,
      healthcare utilisation, health outcomes or costs (expenditures). DATA COLLECTION
      AND ANALYSIS: Two review authors independently extracted data and assessed study
      limitations. We reanalysed time series data for studies with sufficient data, if
      appropriate analyses were not reported. MAIN RESULTS: We included 32 full-text
      articles (17 new) reporting evaluations of 39 different interventions (one study 
      Newhouse 1993 - comprises five papers). We excluded from this update eight
      controlled before-after studies included in the previous version of this review,
      because they included only one site in their intervention or control groups. Five
      papers evaluated caps, and six evaluated a cap with co-insurance and a ceiling.
      Six evaluated fixed co-payment, two evaluated tiered fixed co-payment, 10
      evaluated a ceiling with fixed co-payment and 10 evaluated a ceiling with co
      insurance. Only one evaluation was a randomised trial. The certainty of the
      evidence was found to be generally low to very low.Increasing the amount of money
      that people pay for medicines may reduce insurers' medicine expenditures and may
      reduce patients' medicine use. This may include reductions in the use of life
      sustaining medicines as well as medicines that are important in treating chronic
      conditions and medicines for asymptomatic conditions. These types of
      interventions may lead to small decreases in or uncertain effects on healthcare
      utilisation. We found no studies that reliably reported the effects of these
      types of interventions on health outcomes. AUTHORS' CONCLUSIONS: The diversity of
      interventions and outcomes addressed across studies and differences in settings,
      populations and comparisons made it difficult to summarise results across
      studies. Cap and co-payment polices may reduce the use of medicines and reduce
      medicine expenditures for health insurers. However, they may also reduce the use
      of life-sustaining medicines or medicines that are important in treating chronic,
      including symptomatic, conditions and, consequently, could increase the use of
      healthcare services. Fixed co-payment with a ceiling and tiered fixed co-payment
      may be less likely to reduce the use of essential medicines or to increase the
      use of healthcare services.

PMID- 25966338
TI  - Phase-contrast zoom tomography reveals precise locations of macrophages in mouse
      lungs.
AB  - We have performed x-ray phase-contrast tomography on mouse lung tissue. Using a
      divergent x-ray beam generated by nanoscale focusing, we used zoom tomography to
      produce three-dimensional reconstructions with selectable magnification,
      resolution, and field of view. Thus, macroscopic tissue samples extending over
      several mm can be studied in sub-cellular-level structural detail. The zoom
      capability and, in particular, the high dose efficiency are enabled by the near
      perfect exit wavefront of an optimized x-ray waveguide channel. In combination
      with suitable phase-retrieval algorithms, challenging radiation-sensitive and low
      contrast samples can be reconstructed with minimal artefacts. The dose efficiency
      of the method is demonstrated by the reconstruction of living macrophages both
      with and without phagocytized contrast agents. We also used zoom tomography to
      visualize barium-labelled macrophages in the context of morphological structures
      in asthmatic and healthy mouse lung tissue one day after intratracheal
      application. The three-dimensional reconstructions showed that the macrophages
      predominantly localized to the alveoli, but they were also found in bronchial
      walls, indicating that these cells might be able to migrate from the lumen of the
      bronchi through the epithelium. 

PMID- 25966339
TI  - Efficacy and Safety of Antiretroviral Therapy Initiated One Week after
      Tuberculosis Therapy in Patients with CD4 Counts < 200 Cells/MUL: TB-HAART Study,
      a Randomized Clinical Trial.
AB  - BACKGROUND: Given the high death rate the first two months of tuberculosis (TB)
      therapy in HIV patients, it is critical defining the optimal time to initiate
      combination antiretroviral therapy (cART). METHODS: A randomized, open-label,
      clinical trial comparing efficacy and safety of efavirenz-based cART initiated
      one week, four weeks, and eight weeks after TB therapy in patients with baseline
      CD4 count < 200 cells/MUL was conducted. The primary endpoint was all-cause
      mortality rate at 48 weeks. The secondary endpoints were hepatotoxicity-requiring
      interruption of TB therapy, TB-associated immune reconstitution inflammatory
      syndrome, new AIDS defining illnesses, CD4 counts, HIV RNA levels, and AFB smear
      conversion rates. All analyses were intention-to-treat. RESULTS: We studied 478
      patients with median CD4 count of 73 cells/MUL and 5.2 logs HIV RNA randomized to
      week one (n = 163), week four (n = 160), and week eight (n = 155). Sixty-four
      deaths (13.4%) occurred in 339.2 person-years. All-cause mortality rates at 48
      weeks were 25 per 100 person-years in week one, 18 per 100 person-years in week
      four and 15 per 100 person-years in week eight (P = 0.2 by the log-rank test).
      All-cause mortality incidence rate ratios in subgroups with CD4 count below 50
      cells/MUL versus above were 2.8 in week one (95% CI 1.2-6.7), 3.1 in week four
      (95% CI 1.2-8.6) and 5.1 in week eight (95% CI 1.8-16). Serum albumin < 3 gms/dL
      (adjusted HR, aHR = 2.3) and CD4 < 50 cells/MUL (aHR = 2.7) were independent
      predictors of mortality. Compared with similar subgroups from weeks four and
      eight, first-line TB treatment interruption was high in week one deaths (P =
      0.03) and in the CD4 subgroup <50 cells/MUL (P = 0.02). CONCLUSIONS:
      Antiretroviral therapy one week after TB therapy doesn't improve overall
      survival. Despite increased mortality with CD4 < 50 cells/MUL, we recommend cART
      later than the first week of TB therapy to avoid serious hepatotoxicity and
      treatment interruption. TRIAL REGISTRATION: ClinicalTrials.gov NCT 01315301.

PMID- 25966340
TI  - Attentional bias to respiratory- and anxiety-related threat in children with
      asthma.
AB  - This study investigated attentional biases in children with asthma. The study
      aimed at testing whether children with asthma are vigilant to asthma and/or
      anxiety cues. Thirty-six children (18 with asthma and 18 healthy controls) aged 9
      12 completed a computerised dot probe task designed to measure attentional bias
      to three different categories of words: asthma, anxiety symptom and general
      negative emotion. Main caregiver anxiety was also assessed, as was frequency of
      inhaler use for those with asthma. Children with asthma showed an attentional
      bias towards asthma words but not anxiety or general negative emotion words.
      Children without asthma showed no significant attentional biases to any word
      categories. Caregiver anxiety was correlated with asthma word attentional bias in
      the asthma group. The findings indicate that attentional bias is present in
      children with asthma. Further research is required to ascertain if this
      exacerbates or maintains health-related problems. 

PMID- 25966342
TI  - Do incompatible arguments cause extensive processing in the evaluation of
      arguments? The role of congruence between argument compatibility and argument
      quality.
AB  - Previous studies have demonstrated that arguments incompatible with prior beliefs
      are subjected to more extensive refutational processing, scrutinized longer, and
      judged to be weaker than arguments compatible with prior beliefs. However, this
      study suggests whether extensive processing is implemented when evaluating
      arguments is not decided by argument compatibility, but by congruence between two
      evaluating tendencies elicited by both argument compatibility and argument
      quality. Consistent with this perspective, the results of two experiments show
      that relative to congruent arguments, participants judged arguments eliciting
      incongruent evaluating tendencies as less extreme in strength, spent more time,
      and felt more hesitant generating strength judgments for them. The results also
      show that it is mainly incongruent arguments, not congruent arguments, whose
      strength ratings were more closely associated with the perceived personal
      importance of the issue, which intensified the tendency to evaluate arguments
      depending on argument compatibility. These results suggest that it is the
      incongruity between argument compatibility and argument quality, and not simply
      the argument compatibility, that plays a more important role in activating an
      extensive processing in the evaluation of arguments. 

PMID- 25966341
TI  - Perioperative cerebral ischemia promote infiltrative recurrence in glioblastoma.
AB  - BACKGROUND: Hypoxia is a key driver for infiltrative growth in experimental
      gliomas. It has remained elusive whether tumor hypoxia in glioblastoma patients
      contributes to distant or diffuse recurrences. We therefore investigated the
      influence of perioperative cerebral ischemia on patterns of progression in
      glioblastoma patients. METHODS: We retrospectively screened MRI scans of 245
      patients with newly diagnosed glioblastoma undergoing resection for perioperative
      ischemia near the resection cavity. 46 showed relevant ischemia nearby the
      resection cavity. A control cohort without perioperative ischemia was generated
      by a 1:1 matching using an algorithm based on gender, age and adjuvant treatment.
      Both cohorts were analyzed for patterns of progression by a blinded
      neuroradiologist. RESULTS: The percentage of diffuse or distant recurrences at
      first relapse was significantly higher in the cohort with perioperative ischemia
      (61.1%) compared to the control cohort (19.4%). The results of the control cohort
      matched well with historical data. The change in patterns of progression was not
      associated with a difference in survival. CONCLUSIONS: This study reveals an
      unrecognized association of perioperative cerebral ischemia with distant or
      diffuse recurrence in glioblastoma. It is the first clinical study supporting the
      concept that hypoxia is a key driver of infiltrative tumor growth in glioblastoma
      patients.

PMID- 25966343
TI  - Introduction: basic biology of the renal endothelin system.

PMID- 25966344
TI  - Endothelin receptors and their antagonists.
AB  - All three members of the endothelin (ET) family of peptides, ET-1, ET-2, and ET
      3, are expressed in the human kidney, with ET-1 being the predominant isoform. ET
      1 and ET-2 bind to two G-protein-coupled receptors, ETA and ETB, whereas at
      physiological concentrations ET-3 has little affinity for the ET(A) receptor. The
      human kidney is unusual among the peripheral organs in expressing a high density
      of ET(B). The renal vascular endothelium only expresses the ET(B) subtype and ET
      1 acts in an autocrine or paracrine manner to release vasodilators. Endothelial
      ETB in kidney, as well as liver and lungs, also has a critical role in scavenging
      ET-1 from the plasma. The third major function is ET-1 activation of ET(B) in in
      the nephron to reduce salt and water re-absorption. In contrast, ET(A)
      predominate on smooth muscle, causing vasoconstriction and mediating many of the
      pathophysiological actions of ET-1. The role of the two receptors has been
      delineated using highly selective ET(A) (BQ123, TAK-044) and ET(B) (BQ788)
      peptide antagonists. Nonpeptide antagonists, bosentan, macitentan, and
      ambrisentan, that are either mixed ET(A)/ET(B) antagonists or display ET(A)
      selectivity, have been approved for clinical use but to date are limited to
      pulmonary hypertension. Ambrisentan is in clinical trials in patients with type 2
      diabetic nephropathy. This review summarizes ET-receptor antagonism in the human
      kidney, and considers the relative merits of selective versus nonselective
      antagonism in renal disease.

PMID- 25966345
TI  - Endothelin and renal ion and water transport.
AB  - The renal tubular epithelial cells produce more endothelin-1 (ET-1) than any
      other cell type in the body. Moving down the nephron, the amount of ET-1 produced
      appears fairly consistent until reaching the inner medullary collecting duct,
      which produces at least 10 times more ET-1 than any other segment. ET-1 inhibits
      Na(+) transport in all parts of the nephron through activation of the ETB
      receptor, and, to a minor extent, the ETA receptor. These effects are most
      prominent in the collecting duct where ETB-receptor activation inhibits activity
      of the epithelial Na(+) channel. Effects in other parts of the nephron include
      inhibition of Na(+)/H(+) exchange in the proximal tubule and the Na(+), K(+),
      2Cl(-) co-transporter in the thick ascending limb. In general, the renal
      epithelial ET-1 system is an integral part of the body's response to a high salt
      intake to maintain homeostasis and normal blood pressure. Loss of ETB-receptor
      function results in salt-sensitive hypertension. The role of renal ET-1 and how
      it affects Na(+) and water transport throughout the nephron is reviewed. 

PMID- 25966348
TI  - Endothelin antagonism and hypertension: an evolving target.
AB  - The impact of endothelin antagonism for the management of hypertension is a topic
      explored in multiple preclinical and clinical studies. Endothelin-receptor
      antagonists are an effective therapy for primary and resistant hypertension, but
      they are not widely used. This is owing to side effects shown in large clinical
      trials as well as the availability of many alternative agents to manage blood
      pressure effectively. However, the study of endothelin and its close ties to
      hypertension is evolving. Recent preclinical studies have explored new
      applications of more selective endothelin-receptor antagonists. The studies
      suggested that patients with certain subtypes of hypertension may benefit more
      from endothelin-receptor blockade than simply patients with primary hypertension.
      We review this and other data on this topic. 

PMID- 25966346
TI  - Endothelin and the renal microcirculation.
AB  - Endothelin (ET) is one of the most potent renal vasoconstrictors. Endothelin
      plays an essential role in the regulation of renal blood flow, glomerular
      filtration, sodium and water transport, and acid-base balance. ET-1, ET-2, and ET
      3 are the three distinct endothelin isoforms comprising the endothelin family. ET
      1 is the major physiologically relevant peptide and exerts its biological
      activity through two G-protein-coupled receptors: ET(A) and ET(B). Both ET(A) and
      ET(B) are expressed by the renal vasculature. Although ET(A) are expressed mainly
      by vascular smooth muscle cells, ET(B) are expressed by both renal endothelial
      and vascular smooth muscle cells. Activation of the endothelin system, or
      overexpression of downstream endothelin signaling pathways, has been implicated
      in several pathophysiological conditions including hypertension, acute kidney
      injury, diabetic nephropathy, and immune nephritis. In this review, we focus on
      the effects of endothelin on the renal microvasculature, and update recent
      findings on endothelin in the regulation of renal hemodynamics.

PMID- 25966349
TI  - Endothelin in nondiabetic chronic kidney disease: preclinical and clinical
      studies.
AB  - The incidence and prevalence of chronic kidney disease (CKD) is increasing.
      Despite current therapies, many patients with CKD have suboptimal blood pressure,
      ongoing proteinuria, and develop progressive renal dysfunction. Further
      therapeutic options therefore are required. Over the past 20 years the endothelin
      (ET) system has become a prime target. Experimental models have shown that ET-1,
      acting primarily via the endothelin-A receptor, plays an important role in the
      development of proteinuria, glomerular injury, fibrosis, and inflammation.
      Subsequent animal and early clinical studies using ET-receptor antagonists have
      suggested that theses therapies may slow renal disease progression primarily
      through blood pressure and proteinuria reduction. This review examines the
      current literature regarding the ET system in nondiabetic CKD. 

PMID- 25966350
TI  - Et and diabetic nephropathy: preclinical and clinical studies.
AB  - The incidence of progressive kidney disease associated with diabetes continues to
      increase worldwide. Only partial renoprotection is achieved by current standard
      therapy with angiotensin-converting enzyme inhibitors and/or angiotensin-receptor
      blockers, increasing the need for novel therapeutic approaches. Experimental
      studies have provided evidence of a pathogenic role for endothelin-1 (ET-1) and
      its cognate receptors in the development and progression of diabetic nephropathy.
      ET-1, mainly through the activation of ETA receptor, contributes to renal cell
      injury, inflammation, and fibrosis. In animal models of type 1 and type 2
      diabetes, ETA-selective antagonists have been shown to provide renoprotective
      effects, supplying the rationale for clinical trials in patients with diabetic
      nephropathy with ETA-receptor antagonists administered in addition to renin
      angiotensin system blockade. 

PMID- 25966351
TI  - Endothelin and tubulointerstitial renal disease.
AB  - All components of the endothelin (ET) system are present in renal tubular cells.
      In this review, we summarize current knowledge about ET and the most common
      tubular diseases: acute kidney injury (AKI) and polycystic kidney disease. AKI
      originally was called acute tubular necrosis, pointing to the most prominent
      morphologic findings. Similarly, cysts in polycystic kidney disease, and
      especially in autosomal-dominant polycystic kidney disease, are of tubular
      origin. Preclinical studies have indicated that the ET system and particularly
      ETA receptors are involved in the pathogenesis of ischemia-reperfusion injury,
      although these findings have not been translated to clinical studies. The ET
      system also has been implicated in radiocontrast-dye-induced AKI, however, ET
      receptor blockade in a large human study was not successful. The ET system is
      activated in sepsis models of AKI; the effectiveness of ET blocking agents in
      preclinical studies is variable depending on the model and the ET-receptor
      antagonist used. Numerous studies have shown that the ET system plays an
      important role in the complex pathophysiology associated with cyst formation and
      disease progression in polycystic kidney disease. However, results from selective
      targeting of ET-receptor subtypes in animal models of polycystic kidney disease
      have proved disappointing and do not support clinical trials. These studies have
      shown that a critical balance between ETA and ETB receptor action is necessary to
      maintain structure and function in the cystic kidney. In summary, ETs have been
      implicated in the pathogenesis of several renal tubulointerstitial diseases,
      however, experimental animal findings have not yet led to use of ET blockers in
      human beings. 

PMID- 25966353
TI  - [Not Available].

PMID- 25966352
TI  - Exploring the effect of surface functionality on the self-assembly of
      polyoxopalladate macroions.
AB  - The solution behavior of the two polyoxo-13-palladates(II) ([Pd(II) 13 As(V) 8
      O34 (OH)6 ](8-) and [Pd(II) 13 (As(V) Ph)8 O32 ](6-) ) was studied in detail. We
      discovered that the countercation-mediated attraction is the driving force for
      their self-assembly into larger architectures. However, the presence of phenyl
      groups in the periphery of [Pd(II) 13 (As(V) Ph)8 O32 ](6-) results in an
      enhanced attraction among these polyanions through hydrophobic interactions,
      which leads to completely different trends of assembly size for these two very
      similar clusters when decreasing solvent polarity. An increase of assembly size
      with increasing solvent polarity was observed for [Pd(II) 13 (As(V) Ph)8 O32 ](6
      ) , whereas for [Pd(II) 13 As (V) 8 O34 (OH)6 ](8-) it was the opposite, due to
      the absence of hydrophobic interactions. 

PMID- 25966347
TI  - Endothelin and the glomerulus in chronic kidney disease.
AB  - Endothelin-1 (ET-1) is a 21-amino acid peptide with mitogenic and powerful
      vasoconstricting properties. Under healthy conditions, ET-1 is expressed
      constitutively in all cells of the glomerulus and participates in homeostasis of
      glomerular structure and filtration function. Under disease conditions, increases
      in ET-1 are critically involved in initiating and maintaining glomerular
      inflammation, glomerular basement membrane hypertrophy, and injury of podocytes
      (visceral epithelial cells), thereby promoting proteinuria and
      glomerulosclerosis. Here, we review the role of ET-1 in the function of
      glomerular endothelial cells, visceral (podocytes) and parietal epithelial cells,
      mesangial cells, the glomerular basement membrane, stromal cells, inflammatory
      cells, and mesenchymal stem cells. We also discuss molecular mechanisms by which
      ET-1, predominantly through activation of the ETA receptor, contributes to injury
      to glomerular cells, and review preclinical and clinical evidence supporting its
      pathogenic role in glomerular injury in chronic renal disease. Finally, the
      therapeutic rationale for endothelin antagonists as a new class of
      antiproteinuric drugs is discussed. 

PMID- 25966354
TI  - Modification of pro-inflammatory signaling by dietary components: The plasma
      membrane as a target.
AB  - You are what you eat - this well-known phrase properly describes the phenomenon
      of the effects of diet on acute and chronic inflammation. Several lipids and
      lipophilic compounds that are delivered with food or are produced in situ in
      pathological conditions exert immunomodulatory activity due to their interactions
      with the plasma membrane. This group of compounds includes cholesterol and its
      oxidized derivatives, fatty acids, alpha-tocopherol, and polyphenols. Despite
      their structural heterogeneity, all these compounds ultimately induce changes in
      plasma membrane architecture and fluidity. By doing this, they modulate the
      dynamics of plasma membrane receptors, such as TLR4. This receptor is activated
      by lipopolysaccharide, triggering acute inflammation during bacterial infection,
      which often leads to sepsis and is linked with diverse chronic inflammatory
      diseases. In this review, we discuss how the impact on plasma membrane properties
      contributes to the immunomodulatory activity of dietary compounds, pointing to
      the therapeutic potential of some of them. Also watch the Video Abstract. 

PMID- 25966355
TI  - Complete Chloroplast Genome Sequence of Tartary Buckwheat (Fagopyrum tataricum)
      and Comparative Analysis with Common Buckwheat (F. esculentum).
AB  - We report the chloroplast (cp) genome sequence of tartary buckwheat (Fagopyrum
      tataricum) obtained by next-generation sequencing technology and compared this
      with the previously reported common buckwheat (F. esculentum ssp. ancestrale) cp
      genome. The cp genome of F. tataricum has a total sequence length of 159,272 bp,
      which is 327 bp shorter than the common buckwheat cp genome. The cp gene content,
      order, and orientation are similar to those of common buckwheat, but with some
      structural variation at tandem and palindromic repeat frequencies and junction
      areas. A total of seven InDels (around 100 bp) were found within the intergenic
      sequences and the ycf1 gene. Copy number variation of the 21-bp tandem repeat
      varied in F. tataricum (four repeats) and F. esculentum (one repeat), and the
      InDel of the ycf1 gene was 63 bp long. Nucleotide and amino acid have highly
      conserved coding sequence with about 98% homology and four genes--rpoC2, ycf3,
      accD, and clpP--have high synonymous (Ks) value. PCR based InDel markers were
      applied to diverse genetic resources of F. tataricum and F. esculentum, and the
      amplicon size was identical to that expected in silico. Therefore, these InDel
      markers are informative biomarkers to practically distinguish raw or processed
      buckwheat products derived from F. tataricum and F. esculentum.

PMID- 25966357
TI  - Correction: The aerodynamic cost of head morphology in bats: maybe not as bad as
      it seems.

PMID- 25966356
TI  - Sleep Physiology Alterations Precede Plethoric Phenotypic Changes in R6/1
      Huntington's Disease Mice.
AB  - In hereditary neurodegenerative Huntington's disease (HD), there exists a growing
      consideration that sleep and circadian dysregulations may be important symptoms.
      It is not known, however, whether sleep abnormalities contribute to other
      behavioral deficits in HD patients and mouse models. To determine the precise
      chronology for sleep physiology alterations and other sensory, motor, psychiatric
      and cognitive symptoms of HD, the same R6/1 HD transgenics and their wild-type
      littermates were recorded monthly for sleep electroencephalogram (EEG) together
      with a wide range of behavioral tests according to a longitudinal plan. We found
      an early and progressive deterioration of both sleep architecture and EEG brain
      rhythms in R6/1 mice, which are correlated timely with their spatial working
      memory impairments. Sleep fragmentation and memory impairments were accompanied
      by the loss of delta (1-4 Hz) power in the transgenic mice, the magnitude of
      which increased with age and disease progression. These precocious sleep and
      cognitive impairments were followed by deficits in social behavior, sensory and
      motor abilities. Our data confirm the existence and importance of sleep
      physiology alterations in the widely used R6/1 mouse line and highlight their
      precedence over other plethoric phenotypic changes. The brainwave abnormalities,
      may represent a novel biomarker and point to innovative therapeutic interventions
      against HD.

PMID- 25966358
TI  - Chronic gastritis and enterocolitis associated with Leishmania infection in an 18
      month-old, intact female dog.

PMID- 25966359
TI  - Argumentation based joint learning: a novel ensemble learning approach.
AB  - Recently, ensemble learning methods have been widely used to improve
      classification performance in machine learning. In this paper, we present a novel
      ensemble learning method: argumentation based multi-agent joint learning (AMAJL),
      which integrates ideas from multi-agent argumentation, ensemble learning, and
      association rule mining. In AMAJL, argumentation technology is introduced as an
      ensemble strategy to integrate multiple base classifiers and generate a high
      performance ensemble classifier. We design an argumentation framework named Arena
      as a communication platform for knowledge integration. Through argumentation
      based joint learning, high quality individual knowledge can be extracted, and
      thus a refined global knowledge base can be generated and used independently for
      classification. We perform numerous experiments on multiple public datasets using
      AMAJL and other benchmark methods. The results demonstrate that our method can
      effectively extract high quality knowledge for ensemble classifier and improve
      the performance of classification. 

PMID- 25966360
TI  - Not all are free-living: high-throughput DNA metabarcoding reveals a diverse
      community of protists parasitizing soil metazoa.
AB  - Protists, the most diverse eukaryotes, are largely considered to be free-living
      bacterivores, but vast numbers of taxa are known to parasitize plants or animals.
      High-throughput sequencing (HTS) approaches now commonly replace cultivation
      based approaches in studying soil protists, but insights into common biases
      associated with this method are limited to aquatic taxa and samples. We created a
      mock community of common free-living soil protists (amoebae, flagellates,
      ciliates), extracted DNA and amplified it in the presence of metazoan DNA using
      454 HTS. We aimed at evaluating whether HTS quantitatively reveals true relative
      abundances of soil protists and at investigating whether the expected protist
      community structure is altered by the co-amplification of metazoan-associated
      protist taxa. Indeed, HTS revealed fundamentally different protist communities
      from those expected. Ciliate sequences were highly over-represented, while those
      of most amoebae and flagellates were under-represented or totally absent. These
      results underpin the biases introduced by HTS that prevent reliable quantitative
      estimations of free-living protist communities. Furthermore, we detected a wide
      range of nonadded protist taxa probably introduced along with metazoan DNA, which
      altered the protist community structure. Among those, 20 taxa most closely
      resembled parasitic, often pathogenic taxa. Therewith, we provide the first HTS
      data in support of classical observational studies that showed that potential
      protist parasites are hosted by soil metazoa. Taken together, profound
      differences in amplification success between protist taxa and an inevitable co
      extraction of protist taxa parasitizing soil metazoa obscure the true diversity
      of free-living soil protist communities. 

PMID- 25966361
TI  - Synergistic effects of co-administration of suicide gene expressing mesenchymal
      stem cells and prodrug-encapsulated liposome on aggressive lung melanoma
      metastases in mice.
AB  - The success of conventional suicide gene therapy for cancer treatment is still
      limited because of lack of efficient delivery methods, as well as poor
      penetration into tumor tissues. Mesenchymal stem cells (MSCs) have recently
      emerged as potential vehicles in improving delivery issues. However, these stem
      cells are usually genetically modified using viral gene vectors for suicide gene
      overexpression to induce sufficient therapeutic efficacy. This approach may
      result in safety risks for clinical translation. Therefore, we designed a novel
      strategy that uses non-viral gene vector in modifying MSCs with suicide genes to
      reduce risks. In addition, these cells were co-administrated with prodrug
      encapsulated liposomes for synergistic anti-tumor effects. Results demonstrate
      that this strategy is effective for gene and prodrug delivery, which co-target
      tumor tissues, to achieve a significant decrease in tumor colonization and a
      subsequent increase in survival in a murine melanoma lung metastasis model.
      Moreover, for the first time, we demonstrated the permeability of MSCs within
      tumor nests by using an in vitro 3D tumor spheroid model. Thus, the present study
      provides a new strategy to improve the delivery problem in conventional suicide
      gene therapy and enhance the therapeutic efficacy. Furthermore, this study also
      presents new findings to improve our understanding of MSCs in tumor-targeted gene
      delivery. 

PMID- 25966362
TI  - Flow shear stress differentially regulates endothelial uptake of nanocarriers
      targeted to distinct epitopes of PECAM-1.
AB  - Targeting nanocarriers (NC) to endothelial cell adhesion molecules including
      Platelet-Endothelial Cell Adhesion Molecule-1 (PECAM-1 or CD31) improves drug
      delivery and pharmacotherapy of inflammation, oxidative stress, thrombosis and
      ischemia in animal models. Recent studies unveiled that hydrodynamic conditions
      modulate endothelial endocytosis of NC targeted to PECAM-1, but the specificity
      and mechanism of effects of flow remain unknown. Here we studied the effect of
      flow on endocytosis by human endothelial cells of NC targeted by monoclonal
      antibodies Ab62 and Ab37 to distinct epitopes on the distal extracellular domain
      of PECAM. Flow in the range of 1-8dyn/cm(2), typical for venous vasculature,
      stimulated the uptake of spherical Ab/NC (~180nm diameter) carrying ~50 vs 200
      Ab62 and Ab37 per NC, respectively. Effect of flow was inhibited by disruption of
      cholesterol-rich plasmalemma domains and deletion of PECAM-1 cytosolic tail. Flow
      stimulated endocytosis of Ab62/NC and Ab37/NC via eliciting distinct signaling
      pathways mediated by RhoA/ROCK and Src Family Kinases, respectively. Therefore,
      flow stimulates endothelial endocytosis of Ab/NC in a PECAM-1 epitope specific
      manner. Using ligands of binding to distinct epitopes on the same target molecule
      may enable fine-tuning of intracellular delivery based on the hemodynamic
      conditions in the vascular area of interest. 

PMID- 25966363
TI  - Improved insulin sensitivity after exercise training is linked to reduced plasma
      C14:0 ceramide in obesity and type 2 diabetes.
AB  - OBJECTIVE: To assess the effect of exercise training on insulin sensitivity and
      plasma ceramides in obesity and type 2 diabetes (T2D). METHODS: Twenty-four
      adults with obesity and normal glucose tolerance (NGT, n = 14) or diabetes (n =
      10) were studied before and after a 12-week supervised exercise-training program
      (5 days/week, 1 h/day, 80-85% of maximum heart rate). Changes in body composition
      were assessed using hydrostatic weighing and computed tomography. Peripheral
      tissue insulin sensitivity was assessed by a 40 mU/m(2) /min hyperinsulinemic
      euglycemic clamp. Plasma ceramides (C14:0, C16:0, C18:0, C18:1, C20:0, C24:0, and
      C24:1) were quantified using electrospray ionization tandem mass spectrometry
      after separation with HPLC. RESULTS: Plasma ceramides were similar for the
      subjects with obesity and NGT and the subjects with diabetes, despite differences
      in glucose tolerance. Exercise significantly reduced body weight and adiposity
      and increased peripheral insulin sensitivity in both groups (P < 0.05). In
      addition, plasma C14:0, C16:0, C18:1, and C24:0 ceramide levels were reduced in
      all subjects following the intervention (P < 0.05). Decreases in total (r = 
      0.51, P = 0.02) and C14:0 (r = -0.56, P = 0.009) ceramide were negatively
      correlated with the increase in insulin sensitivity. CONCLUSIONS: Ceramides are
      linked to exercise training-induced improvements in insulin sensitivity, and
      plasma C14:0 ceramide may provide a specific target for investigating lipid
      related insulin resistance in obesity and T2D.

PMID- 25966364
TI  - Abnormal error processing in depressive states: a translational examination in
      humans and rats.
AB  - Depression has been associated with poor performance following errors, but the
      clinical implications, response to treatment and neurobiological mechanisms of
      this post-error behavioral adjustment abnormality remain unclear. To fill this
      gap in knowledge, we tested depressed patients in a partial hospital setting
      before and after treatment (cognitive behavior therapy combined with medication)
      using a flanker task. To evaluate the translational relevance of this metric in
      rodents, we performed a secondary analysis on existing data from rats tested in
      the 5-choice serial reaction time task after treatment with corticotropin
      releasing factor (CRF), a stress peptide that produces depressive-like signs in
      rodent models relevant to depression. In addition, to examine the effect of
      treatment on post-error behavior in rodents, we examined a second cohort of
      rodents treated with JDTic, a kappa-opioid receptor antagonist that produces
      antidepressant-like effects in laboratory animals. In depressed patients,
      baseline post-error accuracy was lower than post-correct accuracy, and, as
      expected, post-error accuracy improved with treatment. Moreover, baseline post
      error accuracy predicted attentional control and rumination (but not depressive
      symptoms) after treatment. In rats, CRF significantly degraded post-error
      accuracy, but not post-correct accuracy, and this effect was attenuated by JDTic.
      Our findings demonstrate deficits in post-error accuracy in depressed patients,
      as well as a rodent model relevant to depression. These deficits respond to
      intervention in both species. Although post-error behavior predicted treatment
      related changes in attentional control and rumination, a relationship to
      depressive symptoms remains to be demonstrated. 

PMID- 25966367
TI  - Self-assembly dynamics and accumulation mechanisms of ultra-fine nanoparticles.
AB  - The self-assembly of nanomaterials into three-dimensional hierarchical structures
      is a fundamental step impacting a large number of synthetic and natural
      processes. These range from the scalable fabrication of nano-devices such as
      batteries, sensors and third generation solar cells to the uptake and
      accumulation of particulate pollution in the lung alveoli. Here, we show that the
      Dynamic behavior of ultra-fine particles (UFP < 100 nm) diverges significantly
      from that of sub- and micro equivalents. For freely diffusing bodies, this leads
      to the formation of stochastically reproducible films that approach the
      morphology and density of ballistically deposited ones. A novel deposition
      mechanism and regime are proposed that successfully capture the full spectrum of
      size-dependent self-assembly dynamics. These findings are a significant step
      toward the engineering of scalable parallel nano-fabrication approaches, and the
      understanding of the interaction of unbound nanostructures with their
      surrounding. 

PMID- 25966368
TI  - Synthesis of nanorod-FeP@C composites with hysteretic lithiation in lithium-ion
      batteries.
AB  - Nanorod-FeP@C composites are synthesized via a one-pot solution reaction of
      ferrocene (Fe(C5H5)2) with excess triphenylphosphine (PPh3) in sealed vacuum
      tubes at 390  degrees C, in which PPh3 is used as both the phosphorus source and
      solvent in the reaction. The structure and lithium storage performance of the as
      prepared nanorod-FeP@C composites are intensively characterized, and it is
      interesting that the composites exhibit an increased capacity during cycling
      serving as anode materials for lithium-ion batteries (LIBs). Meanwhile, mechanism
      investigations reveal that the capacity increase of the composites results from a
      hysteretic lithiation of the nanostructured FeP phase due to the coating of the
      carbon shell in the composites. Meanwhile, cyclic stability investigation shows
      that the composites have a very good cyclic stability that shows potential for
      the composites with a long lifespan as a promising kind of anode material. 

PMID- 25966365
TI  - A molecular model for neurodevelopmental disorders.
AB  - Genes implicated in neurodevelopmental disorders (NDDs) important in cognition
      and behavior may have convergent function and several cellular pathways have been
      implicated, including protein translational control, chromatin modification, and
      synapse assembly and maintenance. Here, we test the convergent effects of methyl
      CpG binding domain 5 (MBD5) and special AT-rich binding protein 2 (SATB2) reduced
      dosage in human neural stem cells (NSCs), two genes implicated in 2q23.1 and
      2q33.1 deletion syndromes, respectively, to develop a generalized model for NDDs.
      We used short hairpin RNA stably incorporated into healthy neural stem cells to
      supress MBD5 and SATB2 expression, and massively parallel RNA sequencing, DNA
      methylation sequencing and microRNA arrays to test the hypothesis that a primary
      etiology of NDDs is the disruption of the balance of NSC proliferation and
      differentiation. We show that reduced dosage of either gene leads to significant
      overlap of gene-expression patterns, microRNA patterns and DNA methylation states
      with control NSCs in a differentiating state, suggesting that a unifying feature
      of 2q23.1 and 2q33.1 deletion syndrome may be a lack of regulation between
      proliferation and differentiation in NSCs, as we observed previously for TCF4 and
      EHMT1 suppression following a similar experimental paradigm. We propose a model
      of NDDs whereby the balance of NSC proliferation and differentiation is affected,
      but where the molecules that drive this effect are largely specific to disease
      causing genetic variation. NDDs are diverse, complex and unique, but the optimal
      balance of factors that determine when and where neural stem cells differentiate
      may be a major feature underlying the diverse phenotypic spectrum of NDDs. 

PMID- 25966369
TI  - Vigilance impossible: Diligence, distraction, and daydreaming all lead to
      failures in a practical monitoring task.
AB  - In laboratory studies of vigilance, participants watch for unusual events in a
      "sit and stare" fashion as their performance typically declines over time. But
      watch keepers in practical settings seldom approach monitoring in such simplistic
      ways and controlled environments. We observed airline pilots performing routine
      monitoring duties in the cockpit. Unlike laboratory studies, pilots' monitoring
      did not deteriorate amidst prolonged vigils. Monitoring was frequently
      interrupted by other pop-up tasks and misses followed. However, when free from
      these distractions, pilots reported copious mind wandering. Pilots often confined
      their mind wandering to times in which their monitoring performance would not
      conspicuously suffer. But when no convenient times were available, pilots mind
      wandered anyway and misses ensued. Real-world monitors may be caught between a
      continuous vigilance approach that is doomed to fail, a dynamic environment that
      cannot be fully controlled, and what may be an irresistible urge to let one's
      thoughts drift. 

PMID- 25966370
TI  - Superhydrophobic and anti-icing properties at overcooled temperature of a
      fluorinated hybrid surface prepared via a sol-gel process.
AB  - A superhydrophobic surface with anti-icing performance has been the focus of
      research, but few studies have reported the effective and low cost strategy that
      met the requirements under overcooled conditions. In this article, the
      fluorinated sol-gel colloid coatings were simply prepared via hydrolytic
      condensation of nanosilica sol, methyltriethoxysilane (MTES) and 3
      [(perfluorohexylsulfonyl)amino]propyltriethoxysilane (HFTES). The multi scale
      morphology and chemical composition of the artificial surfaces were characterized
      by scanning electron microscopy (SEM), atomic force microscopy (AFM) and X-ray
      photoelectron spectroscopy (XPS). The influence of the surface roughness
      structure and fluorinated groups on the wettability and freezing delay time of
      the colloid surface under overcooled conditions were explored. As the HFTES
      content was higher than 6 wt%, the prepared colloid surface showed excellent
      superhydropobicity with a contact angle (CA) of about 166 degrees  at room
      temperature. The CA gradually reduced with the decrease of the temperature. Only
      the samples with high HFTES contents (above 30 wt%) exhibited special
      superhydrophobic and anti-icing properties under freeze temperature. Besides the
      surface roughness structure, the high fluoride enrichment on the surface plays a
      major role in the superhydrophobic and anti-icing properties under overcooled
      conditions. 

PMID- 25966366
TI  - Local-to-remote cortical connectivity in early- and adulthood-onset
      schizophrenia.
AB  - Schizophrenia is increasingly thought of as a brain network or connectome
      disorder and is associated with neurodevelopmental processes. Previous studies
      have suggested the important role of anatomical distance in developing a
      connectome with optimized performance regarding both the cost and efficiency of
      information processing. Distance-related disturbances during development have not
      been investigated in schizophrenia. To test the distance-related miswiring
      profiles of connectomes in schizophrenia, we acquired resting-state images from
      20 adulthood-onset (AOS) and 26 early-onset schizophrenia (EOS) patients, as well
      as age-matched healthy controls. All patients were drug naive and had experienced
      their first psychotic episode. A novel threshold-free surface-based analytic
      framework was developed to examine local-to-remote functional connectivity
      profiles in both AOS and EOS patients. We observed consistent increases of local
      connectivity across both EOS and AOS patients in the right superior frontal
      gyrus, where the connectivity strength was correlated with a positive syndrome
      score in AOS patients. In contrast, EOS but not AOS patients exhibited reduced
      local connectivity within the right postcentral gyrus and the left middle
      occipital cortex. These regions' remote connectivity with their interhemispheric
      areas and brain network hubs was altered. Diagnosis-age interactions were
      detectable for both local and remote connectivity profiles. The functional
      covariance between local and remote homotopic connectivity was present in
      typically developing controls, but was absent in EOS patients. These findings
      suggest that a distance-dependent miswiring pattern may be one of the key
      neurodevelopmental features of the abnormal connectome organization in
      schizophrenia. 

PMID- 25966371
TI  - The emergence of regional immigrant concentrations in USA and Australia: a
      spatial relatedness approach.
AB  - This paper examines the patterns of the US and Australian immigration geography
      and the process of regional population diversification and the emergence of new
      immigrant concentrations at the regional level. It presents a new approach in the
      context of human migration studies, focusing on spatial relatedness between
      individual foreign-born groups as revealed from the analysis of their joint
      spatial concentrations. The approach employs a simple assumption that the more
      frequently the members of two population groups concentrate in the same locations
      the higher is the probability that these two groups can be related. Based on
      detailed data on the spatial distribution of foreign-born groups in US counties
      (2000-2010) and Australian postal areas (2006-2011) we firstly quantify the
      spatial relatedness between all pairs of foreign-born groups and model the
      aggregate patterns of US and Australian immigration systems conceptualized as the
      undirected networks of foreign-born groups linked by their spatial relatedness.
      Secondly, adopting a more dynamic perspective, we assume that immigrant groups
      with higher spatial relatedness to those groups already concentrated in a region
      are also more likely to settle in this region in future. As the ultimate goal of
      the paper, we examine the power of spatial relatedness measures in projecting the
      emergence of new immigrant concentrations in the US and Australian regions. The
      results corroborate that the spatial relatedness measures can serve as useful
      instruments in the analysis of the patterns of population structure and
      prediction of regional population change. More generally, this paper demonstrates
      that information contained in spatial patterns (relatedness in space) of
      population composition has yet to be fully utilized in population forecasting. 

PMID- 25966372
TI  - Based on time and spatial-resolved SERS mapping strategies for detection of
      pesticides.
AB  - For the sensitive and convenient detection of pesticides, several sensing methods
      and materials have been widely explored. However, it is still a challenge to
      obtain sensitive, simple detection techniques for pesticides. Here, the simple
      and sensitive Time-resolved SERS mapping (T-SERS) and Spatial-resolved SERS
      mapping (S-SERS) are presented for detection of pesticides by using Au@Ag NPs as
      SERS substrate. The Time-resolved SERS mapping (T-SERS) is based on state
      translation nanoparticles from the wet state to the dry state to realize SERS
      measurements. During the SERS measurement, adhesive force drives the particles
      closer together and then average interparticle gap becomes smaller. Following,
      air then begins to intersperse into the liquid network and the particles are held
      together by adhesive forces at the solid-liquid-air interface. In the late stage
      of water evaporation, all particles are uniformly distributed. Thus, so called
      hotspots matrix that can hold hotspots between every two adjacent particles in
      efficient space with minimal polydispersity of particle size are achieved,
      accompanying the red-shift of surface plasmon peak and appearance of an optimal
      SPR resonated sharply with excitation wavelength. Here, we found that the T-SERS
      method exhibits the detection limits of 1-2 orders of magnitude higher than that
      of S-SERS. On the other hand, the T-SERS is very simple method with high
      detection sensitivity, better reproducibility (RSD=10.8%) and is beneficial to
      construction of a calibration curve in comparison with that of Spatial-resolved
      SERS mapping (S-SERS). Most importantly, as a result of its remarkable
      sensitivity, T-SERS mapping strategies have been applied to detection of several
      pesticides and the detect limit can down to 1nM for paraoxon, 0.5nM for
      sumithion. In short, T-SERS mapping measurement promises to open a market for
      SERS practical detection with prominent advantages. 

PMID- 25966373
TI  - Preparation and chromatographic evaluation of zwitterionic stationary phases with
      controllable ratio of positively and negatively charged groups.
AB  - The present study described the preparation and application of zwitterionic
      stationary phases (ACS) with controllable ratio of positively charged tertiary
      amine groups and negatively charged carboxyl groups. Various parameters,
      including water content, pH values and ionic strength of the mobile phase, were
      investigated to study the chromatographic characteristics of ACS columns. The
      prepared ACS columns demonstrated a mix-mode retention mechanism composed of
      surface adsorption, partitioning and electrostatic interactions. The elemental
      analysis of different batches of the ACS phases demonstrated good reproducibility
      of the preparation strategy. Additionally, various categories of compounds,
      including nucleosides, water-soluble vitamins, benzoic acid derivatives and basic
      compounds were successively employed to evaluate the separation selectivity of
      the prepared ACS stationary phases. These ACS phases exhibited entirely different
      selectivity and retention behavior from each other for various polar analytes,
      demonstrating the excellent application potential in the analysis of polar
      compounds in HILIC. 

PMID- 25966374
TI  - Analysis and applications of nanoparticles in capillary electrophoresis.
AB  - Nanoparticles (NPs) exhibit unique chemical and physical properties that depend
      on their size, shape, and environment. NPs are emerging as new tools and
      techniques in the analytical study of various materials and in the biological and
      biomedical fields, because of their unique properties. Therefore, the
      quantitative and qualitative characterization of NPs has gathered increasing
      interest. Additionally, the NPs are being used in rapidly developing techniques
      to provide highly sensitive and specific analysis of various materials. Capillary
      electrophoresis (CE) has been demonstrated as a useful analytical tool for the
      characterization of NPs and for the evaluation of biological and biomedical
      studies using NPs because of its simple sample preparation and efficient
      resolution of a diverse size range of compounds. This paper gives a short
      overview of the analysis and applications of NPs in CE systems, with an emphasis
      on biological and biomedical studies. 

PMID- 25966375
TI  - High-throughput and rapid fluorescent visualization sensor of urinary citrate by
      CdTe quantum dots.
AB  - In this paper, we have presented a novel CdTe quantum dots (QDs) based
      fluorescent sensor for visual and turn-on sensing of citrate in human urine
      samples. The europium ion (Eu(3+)) can lead to the fluorescence quenching of
      thioglycollic acid (TGA) modified CdTe QDs due to photoinduced electron transfer
      accompanied by the change of emission color from yellow to orange. Next, addition
      of citrate breaks the preformed assembly because citrate can replace the CdTe
      QDs, based on the fact that the Eu(3+) ion displays higher affinity with citrate
      than the CdTe QDs. Thus the photoinduced electron transfer is switched off, and
      the fluorescence emission of CdTe QDs is rapidly (within 5min) recovered,
      simultaneously, the orange emission color restores to yellow. Such proposed
      strategy may conveniently discriminate the patient of renal stone from normal
      person by naked eyes. In addition to visualization detection, the fluorescence
      responses can be used for well quantifying citrate in the range of 0.67-133MUM.
      So, the present, simple, low-cost and visualized citrate fluorescence sensor has
      great potential in the applications for earlier screening in clinical detection. 

PMID- 25966376
TI  - Mercury(II) trace detection by a gold nanoparticle-modified glassy carbon
      electrode using square-wave anodic stripping voltammetry including a chloride
      desorption step.
AB  - Gold nanoparticles (AuNPs) were deposited on a glassy carbon (GC) substrate by
      constant potential electrolysis and characterized by cyclic voltammetry in H2SO4
      and field emission gun scanning electron microscopy (FEG-SEM). The modified AuNPs
      GC electrode was used for low Hg(II) concentration detection using a Square Wave
      Anodic Stripping Voltammetry (SWASV) procedure which included a chloride
      desorption step. The comparison of the obtained results with our previous work in
      which no desorption step was used showed that this latter step significantly
      improved the analytical performances, providing a three time higher sensitivity
      and a limit of detection of 80pM for 300s preconcentration, as well as a lower
      average standard deviation. The influence of chloride concentration on the AuNPs
      GC electrode response to Hg(II) trace amounts was also studied and its optimal
      value confirmed to be in the 10(-2)M range. Finally, the AuNPs-GC electrode was
      used for the determination of Hg(II) in a natural groundwater sample from south
      of France. By using a preconcentration time of 3000s, a Hg(II) concentration of
      19+/-3pM was found, which compared well with the result obtained by cold vapor
      atomic fluorescence spectroscopy (22+/-2pM). 

PMID- 25966377
TI  - Colorimetric magnetic microspheres as chemosensor for Cu(2+) prepared from
      adamantane-modified rhodamine and beta-cyclodextrin-modified Fe3O4@SiO2 via host
      guest interaction.
AB  - Adamantane-modified salicylrhodamine B and beta-cyclodextrin-modified Fe3O4@SiO2
      were assemblied by host-guest interactions which induced novel inclusion complex
      magnetic nanoparticles (SFIC MNPs) colorimetric sensitive for Cu(2+) being
      prepared. The MNPs exhibit a clear color change from colorless to pink
      selectively and sensitively with the addition of Cu(2+) in the experiments of UV
      visible spectra, and the detection limit measures up to 5.99*10(-6)M in solutions
      of CH3CN-H2O =1:10. The SFIC magnetic nanoparticles are superparamagnetic
      according to magnetic measurements and can be separated and collected easily with
      a commercial magnet in nine seconds. In addition, the microspheres have also
      showed good ability of separating for other ions from aqueous solutions due to a
      large number of hydroxyl groups on the surface. 

PMID- 25966378
TI  - Electrochemical sensing of bisphenol A by graphene-1-butyl-3-methylimidazolium
      hexafluorophosphate modified electrode.
AB  - Simple and low cost sensor for the determination of bisphenol A (BPA) based on
      graphene-1-butyl-3-methylimidazolium hexafluorophosphate (BmimPF6) modified
      glassy carbon electrode was developed. It was an irreversible oxidation process
      of BPA on the modified electrode. Experimental conditions such as modified
      volume, pH, scan rate and accumulation time have been optimized. The modified
      electrode provided a considerable enhancement of BPA oxidation. The
      electrochemical response of BPA on this modified electrode was better than those
      on the graphene modified electrode and bare electrode. The detection limit of BPA
      was 8nM (S/N=3), the linear range was from 20nM to 2uM. The modified electrode
      has been employed for determination of milk and soda spiked BPA successfully. 

PMID- 25966379
TI  - SDS-MoS2 nanoparticles as highly-efficient peroxidase mimetics for colorimetric
      detection of H2O2 and glucose.
AB  - In this work, we find that the peroxidase-like activity of MoS2 nanoparticles
      (NPs) is dependent on the surface charge. Negatively charged sodium dodecyl
      sulfate modified MoS2 nanoparticles (SDS-MoS2 NPs) possess highly-efficient
      peroxidase-like activity. MoS2 NPs with intrinsic peroxidase-like activity were
      synthesized through a simple one-pot hydrothermal route. The peroxidase-like
      activities of different surfactants modified MoS2 NPs were discussed. Compared
      with bare MoS2 NPs and positively charged cetyltrimethyl ammonium bromide
      modified MoS2 NPs, SDS-MoS2 NPs have the best peroxidase-like activity. SDS-MoS2
      NPs can efficiently catalyze the oxidation of 3,3,5,5-tetramethylbenzidine (TMB)
      in the presence of H2O2 to generate a blue product. On basis of this, we have
      successfully established a novel platform for colorimetric detection of H2O2, and
      the detection limit is 0.32MUM. Furthermore, the SDS-MoS2 NPs based platform can
      also be used for high sensitivity and selectivity detection of glucose with a
      wide linear range of 5.0-500MUM by controlling the generation of H2O2 in the
      presence of glucose oxidase. 

PMID- 25966380
TI  - Gold nanoparticles decorated poly-melamine modified glassy carbon sensor for the
      voltammetric estimation of domperidone in pharmaceuticals and biological fluids.
AB  - The electrochemical response of an unmodified glassy carbon (GCE), poly
      melamine/GCE and gold nanoparticle (AuNP)/poly-melamine/GCE is compared in the
      present protocol for the sensitive and selective determination of domperidone
      (DOM). The AuNPs were synthesized in the laboratory and characterized using UV
      visible spectroscopy and Transmission Electron Microscopy (TEM). Melamine was
      electropolymerized onto the glassy carbon surface using cyclic voltammetry and
      was investigated using Field Emission Scanning Electron Microscopy (FE-SEM) and
      Electrochemical Impedance Spectroscopy (EIS). The AuNP/poly-melamine/GCE
      exhibited the best electrochemical response among the three electrodes for the
      electro-oxidation of DOM, that was inferred from the EIS, cyclic and square wave
      voltammetry. The modified sensor showed a sensitive, stable and linear response
      in the concentration range of 0.05-100uM with a detection limit of 6nM. The
      selectivity of the proposed sensor was assessed in the presence of high
      concentration of major interfering molecules as xanthine, hypoxanthine, and uric
      acid. The analytical application of the sensor for the quantification of DOM in
      pharmaceutical formulations and biological fluids as urine and serum was also
      investigated and the results demonstrated a recovery of >95% with R.S.D of <5%. 

PMID- 25966381
TI  - Independent components analysis to increase efficiency of discriminant analysis
      methods (FDA and LDA): Application to NMR fingerprinting of wine.
AB  - Discriminant analysis (DA) methods, such as linear discriminant analysis (LDA) or
      factorial discriminant analysis (FDA), are well-known chemometric approaches for
      solving classification problems in chemistry. In most applications, principle
      components analysis (PCA) is used as the first step to generate orthogonal
      eigenvectors and the corresponding sample scores are utilized to generate
      discriminant features for the discrimination. Independent components analysis
      (ICA) based on the minimization of mutual information can be used as an
      alternative to PCA as a preprocessing tool for LDA and FDA classification. To
      illustrate the performance of this ICA/DA methodology, four representative
      nuclear magnetic resonance (NMR) data sets of wine samples were used. The
      classification was performed regarding grape variety, year of vintage and
      geographical origin. The average increase for ICA/DA in comparison with PCA/DA in
      the percentage of correct classification varied between 6+/-1% and 8+/-2%. The
      maximum increase in classification efficiency of 11+/-2% was observed for
      discrimination of the year of vintage (ICA/FDA) and geographical origin
      (ICA/LDA). The procedure to determine the number of extracted features (PCs, ICs)
      for the optimum DA models was discussed. The use of independent components (ICs)
      instead of principle components (PCs) resulted in improved classification
      performance of DA methods. The ICA/LDA method is preferable to ICA/FDA for
      recognition tasks based on NMR spectroscopic measurements. 

PMID- 25966382
TI  - A glucose biosensor based on partially unzipped carbon nanotubes.
AB  - An amperometric glucose biosensor based on direct electron transfer of glucose
      oxidase (GOD) self-assembled on the surface of partially unzipped carbon
      nanotubes (PUCNTs) modified glassy carbon electrode (GCE) has been successfully
      fabricated. PUCNTs were synthesized via a facile chemical oxidative etching CNTs
      and used as a novel immobilization matrix for GOD. The cyclic voltammetric result
      of the PUCNT/GOD/GCE showed a pair of well-defined and quasi-reversible redox
      peaks with a formal potential of -0.470V and a peak to peak separation of 37mV,
      revealing that the fast direct electron transfer between GOD and the electrode
      has been achieved. It is notable that the glucose determination has been achieved
      in mediator-free condition. The developed biosensor displayed satisfactory
      analytical performance toward glucose including high sensitivity (19.50MUA mM(
      1)cm(-2)), low apparent Michaelis-Menten (5.09mM), a wide linear range of 0-17mM,
      and also preventing the interference from ascorbic acid, uric acid and dopamine
      usually coexisting with glucose in human blood. In addition, the biosensor
      acquired excellent storage stabilities. This facile, fast, environment-friendly
      and economical preparation strategy of PUCNT-GOD may provide a new platform for
      the fabrication of biocompatible glucose biosensors and other types of
      biosensors.

PMID- 25966383
TI  - Co9S8 hollow spheres for enhanced electrochemical detection of hydrogen peroxide.
AB  - This work reports on an experimental investigation of Co9S8 hollow spheres with
      excellent interfacial charge transfer ability for the electrochemical detection
      of hydrogen peroxide and glucose in alkaline environment. The result reveals that
      the Co9S8 hollow spheres exhibit excellent electrocatalytic activity for the
      reduction of hydrogen peroxide. An electrochemical sensor based on Co9S8 can be
      further realized, exhibiting a linear response range from 0.0001 to 11.11mM for
      hydrogen peroxide with a low detection limit of 0.02MUM, and a high sensitivity
      of 267.2mA mol(-1)cm(-2), which is one of the highest values among the non
      enzymatic sensors based on inorganic oxides. The Co9S8 sensor also exhibits good
      response toward glucose at different concentrations. These results demonstrate
      that the as-prepared Co9S8 hollow spheres have a potential application in the
      development of sensors for enzyme-free detection of H2O2 and glucose.

PMID- 25966384
TI  - One-pot synthesis of fluorescent DHLA-stabilized Cu nanoclusters for the
      determination of H2O2.
AB  - A facile one-pot approach has been developed to prepare orange-emitting Cu
      nanoclusters (NCs) using tetrakis(hydroxymethyl)phosphonium chloride as a
      reducing agent and lipoic acid as a capping agent under an alkaline medium at
      room temperature. The as-prepared Cu NCs exhibited excellent water solubility,
      large Stokes shift, long lifetime and good dispersion. After the addition of
      polyvinyl pyrrolidone, the fluorescence intensity of dihydrolipoic acid
      stabilized Cu NCs (DHLA-Cu NCs) was greatly enhanced, and their fluorescence
      signal remained stable for 5 weeks storage in the dark at room temperature. Based
      on H2O2-induced fluorescence quenching, DHLA-Cu NCs showed high sensitivity and
      selectivity for the detection of H2O2 in aqueous solution with a detection limit
      of 0.3MUM, and were applied successfully to the detection of H2O2 in human urine
      samples. 

PMID- 25966385
TI  - Hierarchical hybrid film of MnO2 nanoparticles/multi-walled fullerene nanotubes
      graphene for highly selective sensing of hydrogen peroxide.
AB  - Hierarchical hybrid films of MnO2 nanoparticles/multi-walled fullerene nanotubes
      graphene (MNPs/MWFNTs-GS) have been prepared via a simple wet-chemical method.
      For this purpose, MWFNTs (~300nm in length) are fabricated from tailoring multi
      walled carbon nanotubes (MWCNTs), and then inserted into GS to pile up into a
      hierarchical hybrid film with the in situ formative MNPs. Scanning electron
      microscope, transmission electron microscope and X-ray diffraction are used to
      confirm the morphology and structure of the as-obtained film. The electrochemical
      studies reveal that MNPs/MWFNTs-GS exhibit significantly enhanced
      electrocatalytic activity compared with MNPs/GS, and show a rapid response to
      H2O2 over a wide linear range of 2.0MUM-8.44mM with a high sensitivity of
      206.3MUA mM(-1)cm(-2) and an excellent selectivity. These favorable
      electrochemical detection properties may be mainly attributed to the introduction
      of MWFNTs, which helps to promote the electron/ion transport between MNPs and GS
      and form the hierarchical film structure.

PMID- 25966386
TI  - Ultra-trace analysis of plutonium by thermal ionization mass spectrometry with a
      continuous heating technique without chemical separation.
AB  - Thermal ionization mass spectrometry (TIMS) with a continuous heating technique
      is known as an effective method for measuring the isotope ratio in trace amounts
      of uranium. In this study, the analytical performance of thermal ionization mass
      spectrometry with a continuous heating technique was investigated using a
      standard plutonium solution (SRM 947). The influence of the heating rate of the
      evaporation filament on the precision and accuracy of the isotope ratios was
      examined using a plutonium solution sample at the fg level. Changing the heating
      rate of the evaporation filament on samples ranging from 0.1fg to 1000fg revealed
      that the influence of the heating rate on the precision and accuracy of the
      isotope ratios was slight around the heating rate range of 100-250mA/min. All of
      the isotope ratios of plutonium (SRM 947), (238)Pu/(239)Pu, (240)Pu/(239)Pu,
      (241)Pu/(239)Pu and (242)Pu/(239)Pu, were measured down to sample amounts of
      70fg. The ratio of (240)Pu/(239)Pu was measured down to a sample amount of 0.1fg,
      which corresponds to a PuO2 particle with a diameter of 0.2MUm. Moreover, the
      signals of (239)Pu could be detected with a sample amount of 0.03fg, which
      corresponds to the detection limit of (239)Pu of 0.006fg as estimated by the 3
      sigma criterion. (238)Pu and (238)U were clearly distinguished owing to the
      difference in the evaporation temperature between (238)Pu and (238)U. In
      addition, (241)Pu and (241)Am formed by the decay of (241)Pu can be discriminated
      owing to the difference in the evaporation temperature. As a result, the ratios
      of (238)Pu/(239)Pu and (241)Pu/(239)Pu as well as (240)Pu/(239)Pu and
      (242)Pu/(239)Pu in plutonium samples could be measured by TIMS with a continuous
      heating technique and without any chemical separation processes. 

PMID- 25966387
TI  - Nanocrystal-based electrochemiluminescence sensor for cell detection with Au
      nanoparticles and isothermal circular double-assisted signal amplification.
AB  - Here we have developed a sensitive cancer cell amplified detection method which
      combined Au NPs enhanced electrochemiluminescence (ECL) of CdS nanocrystals (NCs)
      film, with isothermal circular amplification reaction of polymerase. In DNA
      circular amplification detection system, hairpin DNA beacon/Au NPs composite
      modified CdS NCs film was used as an ECL emitter. Messenger DNA is hybridized
      with the aptamer modified on magnetic beads (MBs) to form MB-Au bioconjugates. In
      the presence of HL-60 cell, the aptamer would conjugate with the glycoprotein at
      cell surface and messenger DNA sequence would be released. The released messenger
      DNA sequence was then introduced into the cycle amplification system to trigger
      circular polymerizations. This assay allows us to determine the released
      messenger DNA equivalent to 10 cells and exhibits a significant specificity for
      HL-60 cells. 

PMID- 25966388
TI  - Fabrication and evaluation of an organic monolithic column based upon the
      polymerisation of hexyl methacrylate with 1,6-hexanediol ethoxylate diacrylate
      for the separation of small molecules by capillary liquid chromatography.
AB  - This paper describes the fabrication of a new porous monolith, prepared in 100MUm
      i.d. capillaries by the co-polymerisation of hexyl methacrylate with 1,6
      hexanediol ethoxylate diacrylate, poly (HMA-co-1,6 HEDA), in the presence of
      azobisisobutyronitrile, 1, 4-butanediol and 1-propanol were used as porogens for
      the monoliths; the monoliths were then used as a stationary phase for capillary
      liquid chromatography. Two cross linkers namely 1,6 HEDA and EDMA were utilised
      in order to investigate the effects of cross linker length on the separation
      efficiency of small molecules, and it was found that the efficiency of the
      separation improved tenfold when using the longer cross linker, 1,6 HEDA. This
      improvement is associated with the increase in number of methylene groups which
      resulted in an increased number of mesopores, less than 50nm. The 1,6 HEDA based
      monolith showed a high porosity (90%) and no evidence of swelling or shrinking
      with the use of organic solvents. Moreover, the 1,6 HEDA monolith demonstrated
      high reproducibility for the separation of the retained compounds anisole and
      naphthalene; these showed retention time RSDs of 1.79% and 2.74% respectively.
      The fabricated monolith also demonstrated high selectivity for neutral non-polar
      molecules, weak acids, and basic molecules. The asymmetry factors for basic
      molecules (nortriptyline and amitriptyline) were 1.5 and 1.3 respectively,
      indicating slight tailing, which is often noticeable on silica based phases due
      to secondary interactions between basic moieties and the hydroxyl groups of the
      silica. 

PMID- 25966389
TI  - Micelle-assisted signaling of peracetic acid by the oxidation of pyreneboronic
      acid via monomer-excimer switching.
AB  - A simple fluorescent probe for the industrial oxidant peracetic acid (PAA) was
      investigated. PAA-assisted oxidative conversion of pyrene-1-boronic acid into 1
      hydroxypyrene was used as the signaling tool. Pyreneboronic acid was found to
      display selective signaling behavior, being more responsive to PAA than to other
      commonly used practical oxidants such as H2O2 and HOCl. The changes in pyrene
      monomer fluorescence to excimer were used in the quantitative analysis of PAA.
      When using the surfactant hexadecyltrimethylammonium bromide as a micellar
      additive, the signaling of PAA was markedly enhanced. Selective fluorescence
      signaling of PAA by pyrene-1-boronic acid with a detection limit of 1.5*10(-6)M
      in aqueous environment was successfully achieved. 

PMID- 25966390
TI  - Novel spectrophotometric method for detection and estimation of butanol in
      acetone-butanol-ethanol fermenter.
AB  - A new, simple, rapid and selective spectrophotometric method has been developed
      for detection and estimation of butanol in fermentation broth. The red colored
      compound, produced during reduction of diquat-dibromide-monohydrate with 2
      mercaptoethanol in aqueous solution at high pH (>13), becomes purple on phase
      transfer to butanol and gives distinct absorption at lambda520nm. Estimation of
      butanol in the fermentation broth has been performed by salting out extraction
      (SOE) using saturated K3PO4 solution at high pH (>13) followed by absorbance
      measurement using diquat reagent. Compatibility and optimization of diquat
      reagent concentration for detection and estimation of butanol concentration in
      the fermentation broth range was verified by central composite design. A standard
      curve was constructed to estimate butanol in acetone-ethanol-butanol (ABE)
      mixture under optimized conditions. The spectrophotometric results for butanol
      estimation, was found to have 87.5% concordance with the data from gas
      chromatographic analysis. 

PMID- 25966391
TI  - Single strand DNA functionalized single wall carbon nanotubes as sensitive
      electrochemical labels for arsenite detection.
AB  - In this work, a simple and sensitive electrochemical strategy for arsenite
      detection based on the ability of arsenite bound to single-strand DNA (ssDNA) and
      the signal transduction of single wall carbon nanotubes (SWCNTs) is developed. To
      realize this purpose, the ssDNA/SWCNTs complexes were formed at first by making
      ssDNA wrapped around SWCNTs via pi-stacking. In the presence of arsenite, the
      arsenite could strongly bind with the G/T bases of ssDNA and decrease the pi-pi
      interaction between ssDNA and SWCNTs, resulting in a certain amount of ssDNA
      dissociating from the complexes. The separated SWCNTs were selectively assembled
      on the self-assembled monolayer (SAM) modified Au electrode. Then the SWCNTs onto
      the SAM-modified Au electrode substantially restored heterogeneous electron
      transfer that was almost totally blocked by the SAM. The assembled SWCNTs could
      generate a considerably sensitive and specific tactic for signal transduction,
      which was related to the concentration of the arsenite. Through detecting the
      currents mediated by SWCNTs, a linear response to concentration of arsenite
      ranging from 0.5 to 10ppb and a detection limit of 0.5ppb was readily achieved
      with desirable specificity and sensitivity. Such a SWCNTs-based biosensor creates
      a simple, sensitive, nonradioactive route for detection of arsenite. In addition,
      this demonstration provides a new approach to fabrication of stable biosensors
      with favorable electrochemical properties believed to be appealing to
      electroanalytical applications. 

PMID- 25966392
TI  - Development of on-line FTIR spectroscopy for siloxane detection in biogas to
      enhance carbon contactor management.
AB  - Activated carbon filters are used to limit engine damage by siloxanes when biogas
      is utilised to provide electricity. However, carbon filter siloxane removal
      performance is poorly understood as until recently, it had not been possible to
      measure siloxanes on-line. In this study, on-line Fourier Transform Infrared
      (FTIR) spectroscopy was developed to measure siloxane concentration in real
      biogas both upstream (86.1-157.5mg m(-3)) and downstream (2.2-4.3mg m(-3)) of
      activated carbon filters. The FTIR provided reasonable precision upstream of the
      carbon vessel with a root mean square error of 10% using partial least squares
      analysis. However, positive interference from volatile organic carbons was
      observed in downstream gas measurements limiting precision at the outlet to an
      RMSE of 1.5mg m(-3) (47.8%). Importantly, a limit of detection of 3.2mg m(-3) was
      identified which is below the recommended siloxane limit and evidences the
      applicability of on-line FTIR for this application.

PMID- 25966393
TI  - Positional analysis of phosphatidylcholine and phosphatidylethanolamine via LC
      with a charged aerosol detector.
AB  - A new method for the positional analysis of egg yolk phospholipids (PLs)
      (phosphatidylcholine-PC, phosphatidylethanolamine-PE) using liquid chromatography
      with charge aerosol detector (CAD) is described. The method is based on six-step
      procedure: 1) extraction of phospholipids from tissue sample, 2) separation of
      lipid classes by solid phase extraction (SPE), 3) complete regiospecific
      hydrolysis of phospholipids by phospholipase A2 (PLA2), 4) separation of reaction
      products (fatty acids from sn-2 position and 1-acyl lysophospholipids) by SPE, 5)
      chemical hydrolysis of 1-acyl lysophospholipids, and 6) analysis of obtained
      fatty acids by LC with charge aerosol detection (CAD). Total time of enzymatic
      hydrolysis of PLs ranged from 10-30min. The reaction products were separated by
      SPE in three-step gradient elution procedure. Chloroform: methanol mixtures were
      used as eluents to obtain pure fractions of FAs from sn-2 position of PL and 1
      acyl lysoPL (chemically hydrolyzed to FAs). FAs were separated by reversed-phase
      LC using a gradient elution and detected using CAD detector. This combination
      enables determination of all fatty acids in a single analysis, and without the
      sample derivatization. The method was optimized and the response of CAD,
      linearity, precision and sensitivity of the method were studied. 

PMID- 25966394
TI  - Determination of thiram using gold nanoparticles and Resonance Rayleigh
      scattering method.
AB  - A sensitive, simple and novel method was developed to determine thiram fungicide
      in water and plant samples. This method was based on the interaction between gold
      nanoparticles (AuNPs) and thiram fungicide followed by increasing of the
      Resonance Rayleigh scattering (RRS) intensity of nanoparticles. The change in RRS
      intensity (?IRRS) was linearly correlated to the concentration of thiram over the
      range of 1.0-200.0ugL(-1). Thiram can be measured in a short time (4min) without
      any complicated or time-consuming sample pretreatment process. Parameters that
      affect the RRS intensities such as pH, concentration of AuNPs, standing time,
      electrolyte concentration, and coexisting substances were systematically
      investigated and optimized. Interference tests showed that the developed method
      has a very good selectivity and could be used conveniently for the determination
      of thiram. The limit of detection (LOD) and limit of quantification (LOQ) were
      0.3 and 1.0ug L(-1), respectively. Relative standard deviations (RSD) for 20.0
      and 80.0ug L(-1) of thiram were 3.0 and 1.1, respectively. Possible mechanisms
      for the RRS changes of AuNPs in the presence of thiram were discussed and the
      method was successfully applied for the analysis of spiked real water samples and
      fresh plant samples such as tomato and cucumber.

PMID- 25966395
TI  - Ultrasound-assisted emulsification-extraction of orange peel metabolites prior to
      tentative identification by LC-QTOF MS/MS.
AB  - An optimized method for extraction and characterization of compounds present in
      orange peel has been developed. The extraction method allows the simultaneous
      extraction of polar and non-polar compounds by using two immiscible extractants
      (a polar extractant-an 80:20 (v/v) methanol-water mixture, and a non-polar
      extractant-n-hexane). The method is ultrasound-assisted, thus facilitating both
      formation of a stable emulsion between the two immiscible extractants and
      favoring mass-transfer from the solid sample to the liquid phases by a wide
      contact surface. Optimization of the ultrasound-assisted emulsification
      extraction (USAEE) led to the following values as desirability conditions for
      both extracts: 32% amplitude, 0.75s/s duty cycle and 7.5min of extraction time.
      The extracts obtained under these conditions were analyzed by LC-QTOF MS/MS in
      positive and negative ionization modes. Tentative identification of the most
      significant compounds present in each extract allowed their characterization by
      using high resolution tandem mass spectrometry. The optimum extracts provided by
      USAEE were compared by using Principal Component Analysis to those obtained by
      conventional extraction based on maceration. Thus, the composition of the polar
      extracts obtained after 7.5min ultrasonication was similar to that of
      conventional maceration for 4h in both the ionization modes. On the contrary, the
      analysis of non-polar extracts led to different results depending on the
      ionization mode: the ultrasound-assisted extract was similar to those of
      conventional maceration for 10h in negative and positive ionization. This
      behavior could be explained by the contribution of different groups of compounds
      to each ionization mode. 

PMID- 25966396
TI  - Sandwich-format electrochemiluminescence assay for PDGF-BB using quantum dots
      dendrimer nanocomposites as probe.
AB  - This work describes a novel electrochemiluminescence aptasensor for highly
      sensitive detection of platelet-derived growth factor BB (PDGF-BB) using aptamer
      functionalized CdS quantum dots-polyamidoamine as probe (CdS QDs-PAMAM-Apt). CdS
      QDs-PAMAM nanocomposites were synthesized by one-pot synthesis in methanol. The
      prepared nanocomposites were linked with the NH2-aptamer 2 (Apt2) of PDGF-BB to
      form the CdS QDs-PAMAM-Apt2 probe by glutaraldehyde as coupling reagent. For
      constructing the aptasensor, MWCNTs-chitosan composites and NH2-aptamer 1 (Apt1)
      with the same base sequence as Apt2 were immobilized on the electrode by the self
      assembled method to recognize the target protein PDGF-BB. In the presence of PDGF
      BB, the structure of sandwiched format was formed between the Apt1 and the CdS
      QDs-PAMAM-Apt2 probe, thereby resulting in a proportional increase of ECL
      emission. Thanks to the efficient and stable ECL emission of CdS QDs-PAMAM
      dendrimer and the advantage of MWCNTs for accelerating the electron transfer, the
      highly sensitive detection of PDGF-BB with a detection limit of 0.13pM was
      achieved. The linear range is from 0.5pM to 1nM. The present protocol was applied
      to the analysis of PDGF-BB in human serum samples. The recoveries of PDGF-BB in
      human serum samples are 87.2-113% and RSD values are less than 3.6%. 

PMID- 25966397
TI  - Online solid phase extraction liquid chromatography using bonded zwitterionic
      stationary phases and tandem mass spectrometry for rapid environmental trace
      analysis of highly polar hydrophilic compounds - Application for the antiviral
      drug Zanamivir.
AB  - Zanamivir (Za) is a highly polar and hydrophilic antiviral drug used for the
      treatment of influenza A viruses. Za has been detected in rivers of Japan and
      it's environmental occurrence has the risk of inducing antiviral resistant avian
      influenza viruses. In this study, a rapid automated online solid phase extraction
      liquid chromatography method using bonded zwitterionic stationary phases and
      tandem mass spectrometry (SPE/LC-MS/MS) for trace analysis of Za was developed.
      Furthermore, an internal standard (IS) calibration method capable of quantifying
      Za in Milli-Q, surface water, sewage effluent and sewage influent was evaluated.
      Optimum pre-extraction sample composition was found to be 95/5 v/v
      acetonitrile/water sample and 1% formic acid. The developed method showed
      acceptable linearities (r(2)>=0.994), filtration recovery (>=91%), and intra-day
      precisions (RSD<=16%), and acceptable and environmentally relevant LOQs (<=20ngL(
      1)). Storage tests showed no significant losses of Za during 20 days and +4/-20
      degrees C (<=12%) with the exception of influent samples, which should be kept at
      -20 degrees C to avoid significant Za losses. The applicability of the method was
      demonstrated in a study on phototransformation of Za in unfiltered and filtered
      surface water during 28 days of artificial UV irradiation exposure. No
      significant (<=12%) phototransformation was found in surface water after 28 days
      suggesting a relatively high photostability of Za and that Za should be of
      environmental concern. 

PMID- 25966398
TI  - Highly sensitive determination of sulfonamides in environmental water samples by
      sodium dodecylbenzene sulfonate enhanced micro-solid phase extraction combined
      with high performance liquid chromatography.
AB  - Sulfonamides are important antibiotics, and have achieved great applications.
      However they also impose serious threat on the environment and human health when
      they enter into environment by various ways. Present study developed a new
      determination method for six sulfonamides such as sulfadiazine, sulfamerazine,
      sulfamethazine, sulfadimethoxine, sulfamethoxazole and sulfafurazole in water
      samples, which was based on micro-solid phase extraction (MU-SPE) using TiO2
      nanotube arrays as the adsorbent in combination with high performance liquid
      chromatography. Surfactant sodium dodecylbenzene sulfonate (SDBS) was used to
      enhance the extraction performance in this enrichment procedure. The parameters
      that affected the extraction efficiency had been investigated. Under the optimal
      conditions, it was observed that there were good linear relationships between the
      peak areas and the concentrations of the sulfonamides. The linear ranges were 1
      200MUg L(-1) for the six sulfonamides with the correlation coefficients in the
      range of 0.998-0.999. The repeatability of the proposed method was satisfactory
      in the range of 2.1-4.4% (RSD, n=6). The limits of detection (LODs) were in the
      range of 0.27-0.6MUg L(-1). The proposed method was validated with real
      environmental samples, and the spiked recoveries were satisfied. These results
      indicated that the proposed method was a good tool for monitoring sulfonamides in
      the water samples.

PMID- 25966399
TI  - Glutamate detection by amino functionalized tetrahedral amorphous carbon
      surfaces.
AB  - In this paper, a novel amperometric glutamate biosensor with glutamate oxidase
      (GlOx) immobilized directly on NH2 functionalized, platinum doped tetrahedral
      amorphous carbon (ta-C) film, has been successfully developed. First, we
      demonstrate that direct GlOx immobilization is more effective on amino-groups
      than on carboxyl- or hydroxyl-groups. Second, we show that anodizing and plasma
      treatments increase the amount of nitrogen and the proportion of protonated amino
      groups relative to amino groups on the aminosilane coating, which subsequently
      results in an increased amount of active GlOx on the surface. This effect,
      however, is found to be unstable due to unstable electrostatic interactions
      between GlOx and NH3(+). We demonstrate the detection of glutamate in the
      concentration range of 10uM-1mM using the NH2 functionalized Pt doped ta-C
      surface. The biosensor showed high sensitivity (2.9nA MUM(-1)cm(-2)), low
      detection limit (10MUM) and good storage stability. The electrode response to
      glutamate was linear in the concentrations ranging from 10uM to 500uM. In
      conclusion, the study shows that GlOx immobilization is most effective on
      aminosilane treated ta-C surface without any pre-treatments and the fabricated
      sensor structure is able to detect glutamate in the micromolar range.

PMID- 25966400
TI  - Quantum dots-based label-free fluorescence sensor for sensitive and non-enzymatic
      detection of caffeic acid.
AB  - We have developed a label-free fluorescence sensor for caffeic acid (CA) by the
      use of CdTe:Zn(2+) quantum dots (CdTe:Zn(2+) QDs) as an output signal. The
      principle of sensor is based on the fluorescence quenching and binding properties
      of Fe(2+) toward QDs and CA, respectively. To provide a fluorescence turn-on mode
      for CA detection, Fe(2+) is first mixed with QDs solution, leading to a low
      fluorescence emission. With the addition of CA, the fluorescence of QDs is
      recovered due to the strong binding interaction between CA and Fe(2+). Thus, a
      QDs-based label-free fluorescence sensor, designed in a simple mix-and-detect
      format, is established for CA detection. This study demonstrated here not only
      offers simple, sensitive and non-enzymatic detection method for CA, but also
      brings to light a new application of QDs in the food analysis. 

PMID- 25966401
TI  - Optical paper-based sensor for ascorbic acid quantification using silver
      nanoparticles.
AB  - In this paper, we demonstrate for the first time the use of silver nanoparticles
      (AgNPs) for colorimetric ascorbic acid (AA) quantification in a paper-based
      sensor. This device is constituted by spot tests modified with AgNPs and silver
      ions bordered by a hydrophobic barrier which provides quantitative and fast
      analysis of AA. In addition, this device is employed as point-of-care monitoring
      using a unique drop of the sample. AgNPs paper-based sensor changed from light
      yellow to gray color after the addition of AA due to nanoparticle growth and
      clusters formation. The color intensities were altered as a function of AA
      concentration which were measured by either a scanner or a homemade portable
      transmittance colorimeter. Under the selected measurement conditions, results
      presented limit of detection which was comparable to analytical laboratory-based
      methodologies. In addition, the sensitivity of our sensor was comparable to the
      standard titration method when real samples were investigated. 

PMID- 25966403
TI  - Application of surfactant-templated ordered mesoporous material as sorbent in
      micro-solid phase extraction followed by liquid chromatography-triple quadrupole
      mass spectrometry for determination of perfluorinated carboxylic acids in aqueous
      media.
AB  - In the present study, micro-solid phase extraction (u-SPE) followed by liquid
      chromatography-triple tandem mass spectrometery (LC-MS/MS) was developed for the
      determination of perfluorocarboxylic acids (PFCAs) at trace levels in water
      samples. The u-SPE device comprised of a porous polypropylene membrane bag
      containing 5mg sorbent. The membrane bag acted as a clean-up filter and prevented
      matrix compounds from interfering with the extraction process. Analysis was
      carried out by LC-MS/MS in negative electrospray ionization mode. MS/MS
      parameters were optimized for multiple reaction monitoring. Calcined and non
      calcined MCM-41, as silica-ordered mesoporous materials, were used as sorbents in
      u-SPE for the extraction of five PFCAs-perfluoropentanoic acid (PFPA),
      perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic
      acid (PFNA), and perfluorodecanoic acid (PFDA)-from aqueous media. The
      performances of these two sorbents were compared with other sorbents such as
      octadecylsilane (C18) modified silica, HayeSep-A, HayeSep-B, and Porapak-R. It
      was found that non-calcined MCM-41 showed better extraction performance for the
      analytes considered. Parameters influencing extraction efficiency, such as
      desorption time, extraction time, desorption solvent, and salt concentration,
      were investigated. The effect of the matrix on MS signals (suppression or
      enhancement) was also evaluated. Only minor effects on ionization efficiencies
      were observed. The developed method proved to be convenient and offered good
      sensitivity and reproducibility. The limits of detection ranged from 0.02 to
      0.08ng L(-1), with a relative standard deviations between 1.9 and 10.5. It was
      successfully applied to the extraction of PFCAs in river and rain water samples.
      As expected from the ubiquitous nature of PFCAs, contamination at low levels was
      detected for some analytes in the samples (with the highest concentration
      recorded for PFOA). Satisfactory relative recoveries ranging between 64% and 127%
      at spiking levels of 10ng L(-1) of each analyte were obtained.

PMID- 25966402
TI  - Analysis of volatile compounds in powdered milk for infant nutrition by direct
      desorption (CIS4-TDU) and GC-MS.
AB  - Direct thermal desorption coupled with the Gas Chromatography-Mass Spectrometry
      (TDU-CIS4-GC-MS) technique applied to powdered milk was used as a novel approach
      for the characterization and quantification, as relative abundance, of volatile
      organic compounds (VOCs). The aim of this study was to exploit the potential
      applications and setup conditions of the CIS4-TDU-GC-MS technique for the
      identification of oxidized or non-oxidized samples of powdered milk for infant
      nutrition, subjected to accelerated aging through the changes in their VOCs
      profile over time. Thermal desorption at 30 degrees C and subsequent cryotrapping
      at -40 degrees C with a Gerstel Liner-in-Liner system allowed a direct thermal
      desorption and cryotrapping of VOCs without any memory effect, thus avoiding
      sample preparation and contamination. The analyses led to the identification of
      several characteristic off-flavors in the oxidized samples, which were used as
      molecular markers to discriminate samples with different oxidation degrees.
      Finally, VOC contaminants possibly present in the packaging can also be
      identified with this technique. 

PMID- 25966404
TI  - A cost-efficient and portable sulfide device with in situ integrating gas
      permeable porous tube isolation and long path absorbance detection.
AB  - A cost-efficient and portable device for detecting sulfide at submicromolar level
      was fabricated by in situ integrating gas-permeable porous tube isolation and
      long path absorbance detection. The device consisted of a pair of petri dish,
      having a diametrically strung porous membrane tube in the top cover. The ends of
      the tube were terminated by a light emitting diode and a photodiode via plugging
      acrylic optical fiber into the light input/output of tees. Sulfide put in the
      bottom dish was liberated by addition of diluted acid through a port on the
      cover. The liberated hydrogen sulfide diffused into the porous membrane tube and
      reacted with alkaline nitroprusside acceptor in the tube. The color change in the
      long path porous membrane tube cell was real-time monitored in the transmission
      mode. The device responded linearly to sulfide concentration over the range of
      0.5-150.0MUmol/L with relative standard deviations less than 5% in all cases. The
      limits of detection for sulfide were within the range 0.2-1.5MUmol/L in aqueous
      standard and newborn calf serum. The device was successfully applied to the
      determination of sulfide in human serum samples. 

PMID- 25966405
TI  - Magnetic graphene solid-phase extraction for the determination of carbamate
      pesticides in tomatoes coupled with high performance liquid chromatography.
AB  - Graphene-based magnetic nanoparticles, comprising zero-valent iron, iron oxide
      oxyhydroxide and graphene, were prepared through a simple one-step synthesis
      method, and subsequently applied to magnetic solid-phase extraction for the
      determination of trace carbamate pesticides in tomatoes coupled with high
      performance liquid chromatography. The properties of the nanocomposites were
      confirmed by using Fourier transform infrared spectroscopy, X-ray photoelectron
      spectroscopy, and vibrating sample magnetometer. The components within the
      nanocomposites endowed the material with high extraction performance and
      manipulative convenience. Compared with reduced graphene oxide, the as-prepared G
      MNPs showed the better extraction efficiencies for the carbamate pesticides
      thanks to the contribution of the iron-containing magnetic nanoparticles to the
      adsorption capacity of the nanocomposites. Various experimental parameters
      affecting the extraction efficiency had been investigated in detail. Under the
      optimal conditions, the method provided high enrichment factors ranging from 364
      to 434, good linearities ranging from 5 to 200ng g(-1) for metolcarb, baygon and
      methiocarb and 10 to 200ng g(-1) for carbofuran and isoprocarb, low limits of
      detection ranging from 0.58 to 2.06ng g(-1), and satisfactory spiked recoveries
      (between 90.34% and 101.98% with the relative standard deviation values from
      1.21% to 5.93%). It was confirmed that this novel method was an efficient
      pretreatment and enrichment procedure and could be successfully applied for
      extraction and determination of trace carbamate pesticides in complex matrices.

PMID- 25966406
TI  - Antioxidant capacity automatic assay based on inline photogenerated radical
      species from L-glutathione-capped CdTe quantum dots.
AB  - This work aimed at the development of a methodology implemented in an automatic
      flow system for determination of the antioxidant capacity in food samples, based
      on the luminol oxidation by inline photogenerated radical species from cadmium
      telluride nanoparticles capped with L-glutathione. Radical species were generated
      inline by a high-power visible light obtained by Light Emitting Diodes (LEDs)
      assembled in a multipumping flow system (MPFS). The use of visible light instead
      of UV radiation allowed the development of a new methodology for antioxidant
      capacity determination, more environment friendly and to circumvent the risk for
      UV photo-induced degradation of sample antioxidant compounds. Additionally, the
      formation of superoxide radical species was theoretically predicted considering
      the variation of the redox potential with the size of CdTe QDs and the values of
      redox potential of the oxidizing and oxidable species present in the irradiated
      medium. The obtained results of trolox equivalent antioxidant capacity (TEAC)
      from the analysis of commercial beverages were compared with the results of ABTS
      and DPPH batch assays through Spearman's-Rho correlation coefficients and no
      correlation was found (for ABTS: rho=0.2, p<0.6 and for DPPH: rho=0.5, p<0.1)
      since the mechanism of action of the proposed methodology was based on the
      scavenging capacity of ROS species rather than the reduction of a colored
      oxidant. An analytical linear response range between 0.0001 and 0.005mmol L(-1)
      of trolox and a limit of detection of 0.00005mmol L(-1) was found. The QDs based
      MPFS methodology allowed a determination rate of about 79h(-1), a total waste
      generation of 20.5mL h(-1) and the consumption of 0.100mg h(-1) of QDs and 2.1mg
      h(-1) of luminol.

PMID- 25966407
TI  - Label-free and homogeneous aptamer proximity binding assay for fluorescent
      detection of protein biomarkers in human serum.
AB  - By using the aptamer proximity binding assay strategy, the development of a label
      free and homogeneous approach for fluorescent detection of human platelet-derived
      growth factor BB (PDGF-BB) is described. Two G-quadruplex forming sequence-linked
      aptamers bind to the PDGF-BB proteins, which leads to the increase in local
      concentration of the aptamers and promotes the formation of the G-quadruplex
      structures. Subsequently, the fluorescent dye, N-methylmesoporphyrin IX, binds to
      these G-quadruplex structures and generates enhanced fluorescence emission signal
      for sensitive detection of PDGF-BB. The association of the aptamers to the PDGF
      BB proteins is characterized by using native polyacrylamide gel electrophoresis.
      The experimental conditions are optimized to reach an estimated detection limit
      of 3.2nM for PDGF-BB. The developed method is also selective and can be applied
      for monitoring PDGF-BB in human serum samples. With the advantages of label-free
      and homogeneous detection, the demonstrated approach can be potentially employed
      to detect other biomarkers in a relatively simple way. 

PMID- 25966408
TI  - Integrated SDS removal and protein digestion by hollow fiber membrane based
      device for SDS-assisted proteome analysis.
AB  - In this work, a novel integrated sample preparation device for SDS-assisted
      proteome analysis was developed, by which proteins dissolved in 4% (w/v) SDS were
      first diluted by 50% methanol, and then SDS was online removed by a hollow fiber
      membrane interface (HFMI) with 50mM ammonium bicarbonate (pH 8.0) as an exchange
      buffer, finally digested by an immobilized enzyme reactor (IMER). To evaluate the
      performance of such an integrated device, bovine serum albumin dissolved in 4%
      (w/v) SDS as a model sample was analyzed; it could be found that similar to that
      obtained by direct analysis of BSA digests without SDS (the sequence coverage of
      60.3+/-1.0%, n=3), with HFMI as an interface for SDS removal, BSA was identified
      with the sequence coverage of 61.0+/-1.0% (n=3). However, without SDS removal by
      HFMI, BSA could not be digested by the IMER and none peptides could be detected.
      In addition, such an integrated sample preparation device was also applied for
      the analysis of SDS extracted proteins from rat brain, compared to those obtained
      by filter-aided sample preparation (FASP), not only the identified protein group
      and unique peptide number were increased by 12% and 39% respectively, but also
      the sample pretreatment time was shortened from 24h to 4h. All these results
      demonstrated that such an integrated sample preparation device would provide an
      alternative tool for SDS assisted proteome analysis. 

PMID- 25966409
TI  - Polyaniline-coated chitosan-functionalized magnetic nanoparticles: Preparation
      for the extraction and analysis of endocrine-disrupting phenols in environmental
      water and juice samples.
AB  - In the present study, chitosan (CHI) functionalized Fe3O4 magnetic microspheres
      coated with polyaniline (PANI) were synthesized for the first time. The chitosan
      functionalized magnetic microspheres (Fe3O4@CHI) were synthesized by a co
      precipitation method, and then aniline was polymerized on the magnetic core. The
      obtained Fe3O4@CHI@PANI microspheres were spherical core-shell structure with
      uniform size at about 100nm with 20-30nm diameter core. The microspheres had a
      high saturation magnetization of 32emu g(-)(1), which was sufficient for magnetic
      separation. The obtained Fe3O4@CHI@PANI magnetic microspheres were applied as
      magnetic adsorbents for the extraction of aromatic compounds via pi-pi
      interaction between polyaniline shell and aromatic compounds. Three endocrine
      disrupting phenols, including bisphenol A (BPA), 2, 4-dichlorophenol (2, 4-DCP),
      and triclosan (TCS) were selected as the model analytes to verify the extraction
      ability of Fe3O4@CHI@PANI. The hydrophilic chitosan-functionalized Fe3O4 core
      (Fe3O4@CHI) improved the dispersibility of Fe3O4@CHI@PANI microspheres, and then
      improve its extraction efficiency. The dominant parameters affecting enrichment
      efficiency were investigated and optimized. Under optimal condition, the proposed
      method was evaluated, and applied to the analysis of phenols in real water and
      juice samples. The results demonstrated the method based on Fe3O4@CHI@PANI
      magnetic microspheres had good linearity (R(2)>0.996), and limits of detection
      (0.10-0.13ng mL(-1)), high repeatability (RSD<6.6%) and good recovery (85.0
      106.7%).

PMID- 25966410
TI  - Label-free aptamer biosensor for thrombin detection based on functionalized
      graphene nanocomposites.
AB  - A label-free and amplified electrochemical impedimetric aptasensor based on
      functionalized graphene nanocomposites (rGO-AuNPs) was developed for the
      detection of thrombin, which played a vital role in thrombosis and hemostasis.
      The thiolated aptamer and dithiothreitol (TBA15-DTT) were firstly immobilized on
      the gold electrode to capture the thrombin molecules, and then aptamer
      functionalized graphene nanocomposites (rGO-TBA29) were used to fabricate a
      sandwich sensing platform for amplifying the impedimetric signals. As numerous
      negative charges of TBA29 on the electrode repelled to the [Fe(CN)6](4-/3-)
      anions, resulting in an obvious amplified charge-transfer resistance (Rct)
      signal. The Rct increase was linearly proportional to the thrombin concentration
      from 0.3 to 50nM and a detection limit of 0.01nM thrombin was achieved. In
      addition, graphene could also be labeled with other probes via electrostatic or
      pi-pi stacking interactions to produce signals, therefore different detection
      methods expanding wide application could be used in this model. 

PMID- 25966411
TI  - Design of a surface plasmon resonance immunoassay for therapeutic drug monitoring
      of amikacin.
AB  - The therapeutic drug monitoring (TDM) of pharmaceutical drugs with narrow
      therapeutic ranges is of great importance in the clinical setting. It provides
      useful information towards the enhancement of drug therapies, aiding in dosage
      control and toxicity risk management. Amikacin is an aminoglycoside antibiotic
      commonly used in neonatal therapies that is indicated for TDM due to the toxicity
      risks inherent in its use. Current techniques for TDM such as high performance
      liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) are
      costly, time consuming, and cannot be performed at the site of action. Over the
      last decades, surface plasmon resonance (SPR) biosensors have become increasingly
      popular in clinical diagnostics due to their ability to detect biomolecular
      interactions in real-time. We present an SPR-based competitive immunoassay for
      the detection of the antibiotic amikacin, suitable for TDM in both adults and
      neonates. We have obtained high specificity and sensitivity levels with an IC50
      value of 1.4ng/mL and a limit of detection of 0.13ng/mL, which comfortably comply
      with the drug's therapeutic range. Simple dilution of serum can therefore be
      sufficient to analyze low-volume real samples from neonates, increasing the
      potential of the methodology for TDM. Compared to current TDM conventional
      methods, this SPR-based immunoassay can provide advantages such as simplicity,
      potential portability, and label-free measurements with the possibility of high
      throughput. This work is the foundation towards the development of an integrated,
      simple use, highly sensitive, fast, and point-of-care sensing platform for the
      opportune TDM of antibiotics and other drugs in a clinical setting. 

PMID- 25966412
TI  - Electrochemical generation of antimony volatile species, stibine, using gold and
      silver mercury amalgamated cathodes and determination of Sb by flame atomic
      absorption spectrometry.
AB  - The electrochemical generation of antimony volatile species (stibine) using Au
      and Ag mercury amalgamated cathodes is described. Compared with some other
      cathode materials commonly used for electrochemical hydride generation,
      performance of the amalgamated cathodes is substantially better in the following
      aspects: higher interference tolerance, higher erosion resistance and longer
      useful working time. Using the amalgamated cathodes, it could be shown that
      interferences from major constituents at high concentrations, especially from
      transition metals, affecting stibine generation are not as significant as they
      are using other cathode types in regards to sensitivity and useful working time.
      Results obtained using the Ag/Hg amalgamated cathode showed a slightly higher
      sensitivity than the corresponding results obtained using the Au/Hg cathode. The
      Au/Hg cathode, which to our knowledge has not previously been used to generate
      stibine, showed considerably longer useful working time than the Ag/Hg one. The
      optimum catholytes for electrolytic generation of stibine (SbH3) from Sb(III) and
      Sb(V) using the Au/Hg electrode were aqueous solutions containing 0.5mol L(-1)
      H2SO4 and 0.5mol L(-1)HCl, respectively. Under optimized conditions, using the
      Au/Hg cathode and comparing to aqueous standards calibration curves, detection
      limits (3sigma) of 0.027ug L(-1) for Sb(III) and 0.056ug L(-1) for Sb(V), were
      obtained. To check accuracy a marine sediment reference material (PACS-2, NRC)
      was analyzed using a method purportedly developed for this task. Good agreement,
      95% confidence, was found between the certified and the experimental values for
      Sb. The proposed method was also applied to the determination of Sb in aqueous
      solutions of marine sediments samples from Comuna de Bajo Alto Provincia de El
      Oro-Ecuador. Recoveries of five replicate determinations of these samples were in
      the range of 98-103% thus showing acceptable accuracy in the analysis of real
      samples.

PMID- 25966413
TI  - Screen-printed electrode modified with carbon black nanoparticles for phosphate
      detection by measuring the electroactive phosphomolybdate complex.
AB  - We report a sensor for phosphate detection based on screen-printed electrodes
      modified with carbon black nanoparticles. The phosphate was measured in
      amperometric mode via electrochemical reduction of molybdophosphate complex.
      Carbon black nanoparticles demonstrated the ability to quantify the
      molybdophosphate complex at a low applied potential. Some analytical parameters
      such as the working solution (sulfuric acid 0.1M), applied potential (0.125V vs
      Ag/AgCl), and molybdate concentration (1mM) were optimized. Using these
      conditions, a linear range of 0.5-100uM was observed with a detection limit of
      0.1uM, calculated as three times the standard deviation of the blank divided by
      the slope of calibration curve. The system was challenged in drinking, river,
      aquarium, and waste water samples yielding satisfactory recovery values in
      accordance with a spectrophotometric reference method which demonstrated the
      suitability of the screen-printed electrode modified with carbon black
      nanoparticles coupled with the use of molybdate to detect phosphate in water
      samples. 

PMID- 25966414
TI  - Dispersive solid phase microextraction with magnetic graphene oxide as the
      sorbent for separation and preconcentration of ultra-trace amounts of gold ions.
AB  - A selective, simple and rapid dispersive solid phase microextraction was
      developed using magnetic graphene oxide (MGO) as an efficient sorbent for the
      separation and preconcentration of gold ions. The MGO was synthesized by means of
      the simple one step chemical coprecipitation method, characterized by X-ray
      diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy and scanning
      electron microscopy (SEM). Gold ions retained by the sorbent were eluted using
      0.5mol L(-)(1) thiourea in 0.1mol L(-1) HCl solution and determined by the flow
      injection flame atomic absorption spectrometry (FI-FAAS). The factors affecting
      the separation and preconcentration of gold were investigated and optimized.
      Under the optimized conditions, the method exhibited a linear dynamic range of
      0.02-100.0ug L(-)(1) with a detection limit of 4ng L(-1) and an enrichment factor
      of 500. The relative standard deviations of 3.2% and 4.7% (n=6) were obtained at
      20ug L(-1) level of gold ions for the intra and the inter day analysis,
      respectively. The method was successfully applied to the determination of gold
      ions in water and waste water samples as well as a certified reference material
      (CCU-1b, copper flotation concentrate).

PMID- 25966415
TI  - Detection of 17beta-estradiol in water samples by a novel double-layer
      molecularly imprinted film-based biosensor.
AB  - This study reports a novel double-layer molecularly imprinted film (MIF)-based
      biosensor for rapid, sensitive and highly selective detection of small molecule
      17beta-estradiol (E2) that is frequently detected in environmental water samples.
      In this system, the modification of gold surface of SPR chip was performed by 1
      dodecanethiol. Then double-layer MIF was generated on the 1-dodecanethiol
      modified gold surface. The non-modified and imprinted surfaces were characterized
      by atomic force microscopy (AFM), scanning electron microscope (SEM) and contact
      angle measurements. Analysis of surface plasmon resonance (SPR) spectroscopy
      showed that the imprinted sensing film displayed good selectivity for E2 compared
      to other analog molecules and NIF. A good linear relationship was obtained
      between the SPR angle and E2 concentrations over a range of 2.50*10(-13)-2.50*10(
      )(9)mol/L (R(2)=0.993) with the lowest measurable concentration of 2.50*10(
      13)mol/L. The sensor can be regenerated with the mixture of acetic acid and PBS
      buffer (v/v=1:9) as a desorption agent over tens of times without significant
      deterioration of the sensor performance. Potential interference of real
      environmental sample matrix was assessed by spiked samples in several waste
      seawater effluents. This portable sensor system can be successfully applied for
      on-site real-time inexpensive and easy-to-use monitoring of E2 or other small
      molecule pollutants in environmental samples such as effluents or water bodies. 

PMID- 25966416
TI  - A simple and sensitive electrochemical immunosensor based on thiol aromatic
      aldehyde as a substrate for the antibody immobilization.
AB  - In this work, a novel sulfur-containing compound with aldehyde groups was
      synthesized, which was used to immobilize antibodies through the covalent bonding
      of the aldehyde groups with amino groups, in which no additional chemical cross
      linker is required. Human IgG was used as a model analyte to fabricate the
      electrochemical immunosensor. Using the proposed immunosensor, IgG was detected
      within the range from 0.01 to 25ng mL(-1) with a detection limit of 0.003ng mL(
      1) obtained by 3 S/N. The simple electrochemical immunosensor had a good
      specificity, stability and reproducibility.

PMID- 25966417
TI  - Evaluation of ionic liquids as alternative solvents for aldolase activity: Use of
      a new automated SIA methodology.
AB  - An automated methodology is proposed for the evaluation of a set of ionic liquids
      (ILs) as alternative reaction media for aldolase based synthetic processes. For
      that, the effect of traditionally used organic solvents and ILs on the activity
      of aldolase was studied by means of a novel automated methodology. The
      implemented methodology is based on the concept of sequential injection analysis
      (SIA) and relies on the aldolase based cleavage of d-fructose-1,6 diphosphate
      (DFDP), to produce dihydroxyacetone phosphate (DHAP) and d-glyceraldehyde-3
      phosphate (G3P). In the presence of FeCl3, 3-methyl-2-benzothiazoline hydrazine
      (MBTH) forms a blue cation that can be measured at 670nm, by combination with
      G3P. The influence of several parameters such as substrate and enzyme
      concentration, temperature, delay time and MBTH and FeCl3 concentration were
      studied and the optimum reaction conditions were subsequently selected. The
      developed methodology showed good precision and a relative standard deviation
      (rsd) that does not exceed 7% also leading to low reagents consumption as well as
      effluent production. Resorting to this strategy, the activity of the enzyme was
      studied in strictly aqueous media and in the presence of dimethylformamide,
      methanol, bmpyr [Cl], hmim [Cl], bmim [BF4], emim [BF4], emim [Ac], bmim [Cl],
      emim [TfMs], emim [Ms] and Chol [Ac] up to 50%. The results show that the
      utilization of ILs as reaction media for aldolase based organic synthesis might
      present potential advantages over the tested conventional organic solvents. The
      least toxic IL found in this study was cho [Ac] that causes a reduction of enzyme
      activity of only 2.7% when used in a concentration of 50%. Generally, it can be
      concluded that ILs based on choline or short alkyl imidazolium moieties
      associated with biocompatible anions are the most promising ILs regarding the
      future inclusion of these solvents in synthetic protocols catalyzed by aldolase. 

PMID- 25966418
TI  - A highly selective and sensitive electrochemical CS-MWCNTs/Au-NPs composite DNA
      biosensor for Staphylococcus aureus gene sequence detection.
AB  - This paper presents a new electrochemical DNA biosensor constructed using a
      substrate electrode composed of a novel nanocomposite material prepared using
      gold nanoparticles (Au-NPs) and multiwalled carbon nanotubes (MWCNTs) and further
      modified with an Au electrode (AuE), which was used as the substrate electrode. A
      single-stranded DNA (ssDNA) probe was immobilized on the Au-NPs/CS-MWCNTs/AuE
      electrode by means of facile gold-thiol affinity, which resulted in hybridization
      with the target ssDNA sequence. Hybridization reactions were assessed by using
      the reduction peak current of methylene blue (MB) as an electrochemical
      indicator. The advantages of the nanomaterials were found to include high surface
      area, favorable electronic properties, and strong electrocatalytic activity. The
      amount of ssDNA adsorbed on the electrode surface was increased and the
      electrochemical response of MB accelerated. The differential pulse voltammetric
      responses of MB were in line with the specific target ssDNA sequence within the
      concentration range 1.0*10(-15)-1.0*10(-8)M with the detection limit 3.3*10(-16)M
      (3sigma). In the colony forming unit (CFU) we were able to detect 10CFU mL(-1)of
      Staphylococcus aureus in the tap water, achieving good discrimination ability
      between one- and three-base mismatched ssDNA sequences. The polymerase chain
      reaction (PCR) amplification products of S. aureus nuc gene sequence were also
      detected with satisfactory results.

PMID- 25966419
TI  - A peroxidase biomimetic system based on Fe3O4 nanoparticles in non-enzymatic
      sensors.
AB  - Magnetic nanoparticles have been applied in many areas of nanomedicine. Sensing
      platforms based on this type of nanoparticles have received attention due to the
      relative low cost and biocompatibility. Biosensor is the most widely investigated
      type of analytical device. This type of sensor combines the physicochemical
      transduction with the incorporation of biological sensing components. Among the
      biological components, enzymes are the most commonly used as sensitive elements.
      However, natural enzymes may exhibit serious disadvantages such as lack of
      stability and loss of catalytic activity after immobilization. The study of
      enzymatic biomimetic systems are of great interest. This study reports the
      development of a new sensor composed of Fe3O4@CTAB and poly(sodium 4
      styrenesulfonate) (PSS) films assembled via Layer-by-Layer (LbL) technique and
      used as peroxidase mimetic systems. Magnetic nanoparticles (MNps) were
      synthesized using thermal decomposition method and further dispersed to aqueous
      medium by ligand modification reaction using cetyltrimethylammonium bromide
      (CTAB). The amperometric detection limit of H2O2 was found to be ca. 103 umol L(
      1). By chronoamperometry, the peroxidase biomimetic sensor exhibited a linear
      response for H2O2 in the range from 100 umol L(-1) to 1.8 mmol L(-1) (R(2) =
      0.994) with sensitivity of 16 nA mol(-1) L. The apparent Michaelis-Menten
      constant was 5.3 mmol L(-1), comparable with some biosensors based on peroxidase
      enzyme. Moreover, the sensor presented a reproducibility of ca. 7.7% (n = 4) and
      their response (response time: 90 s) is not significantly affected in the
      presence of some interferents including K(+), Na(+), Cl(-), Mg(2+), Ca(2+), and
      Uric Acid. 

PMID- 25966420
TI  - Symptom Clusters in People Living with HIV Attending Five Palliative Care
      Facilities in Two Sub-Saharan African Countries: A Hierarchical Cluster Analysis.
AB  - BACKGROUND: Symptom research across conditions has historically focused on single
      symptoms, and the burden of multiple symptoms and their interactions has been
      relatively neglected especially in people living with HIV. Symptom cluster
      studies are required to set priorities in treatment planning, and to lessen the
      total symptom burden. This study aimed to identify and compare symptom clusters
      among people living with HIV attending five palliative care facilities in two sub
      Saharan African countries. METHODS: Data from cross-sectional self-report of
      seven-day symptom prevalence on the 32-item Memorial Symptom Assessment Scale
      Short Form were used. A hierarchical cluster analysis was conducted using Ward's
      method applying squared Euclidean Distance as the similarity measure to determine
      the clusters. Contingency tables, X2 tests and ANOVA were used to compare the
      clusters by patient specific characteristics and distress scores. RESULTS: Among
      the sample (N=217) the mean age was 36.5 (SD 9.0), 73.2% were female, and 49.1%
      were on antiretroviral therapy (ART). The cluster analysis produced five symptom
      clusters identified as: 1) dermatological; 2) generalised anxiety and
      elimination; 3) social and image; 4) persistently present; and 5) a
      gastrointestinal-related symptom cluster. The patients in the first three symptom
      clusters reported the highest physical and psychological distress scores. Patient
      characteristics varied significantly across the five clusters by functional
      status (worst functional physical status in cluster one, p<0.001); being on ART
      (highest proportions for clusters two and three, p=0.012); global distress
      (F=26.8, p<0.001), physical distress (F=36.3, p<0.001) and psychological distress
      subscale (F=21.8, p<0.001) (all subscales worst for cluster one, best for cluster
      four). CONCLUSIONS: The greatest burden is associated with cluster one, and
      should be prioritised in clinical management. Further symptom cluster research in
      people living with HIV with longitudinally collected symptom data to test cluster
      stability and identify common symptom trajectories is recommended.

PMID- 25966422
TI  - Cholangiocarcinoma.

PMID- 25966421
TI  - Head and neck second primary cancer rates in the human papillomavirus era: A
      population-based analysis.
AB  - BACKGROUND: Patients with head and neck cancer are at high risk for second
      primary malignancies. Human papillomavirus (HPV)-driven tumors are generally high
      grade oropharyngeal cancers. We analyzed the incidence of second primary
      malignancy of the head and neck in patients with primary squamous cell carcinoma
      (SCC) of the head and neck and temporal trends in the HPV era. METHODS: The
      Surveillance, Epidemiology, and End Results (SEER) database was queried for
      patients with SCC of the head and neck (range, 1973-2008). Cumulative incidence
      rates of second primary malignancy of the head and neck were compared based on
      competing risk analysis. RESULTS: A total of 104,639 cases were included in this
      study, of which 4616 patients had second primary malignancy of the head and neck.
      Oropharyngeal cancer incidence increased over time. Estimated incidence
      rate/10,000 person-years (105.5, 80.6, and 50.2 for 1973-1989, 1990-1999, and
      2000-2008, respectively) and cumulative incidence rates (10-year rates of 6.68%,
      5.72%, and 4.59% for 1973-1989, 1990-1999, and 2000-2008, respectively) of second
      primary malignancies of the head and neck for patients with oropharyngeal cancer
      decreased over time (p < .001). The second primary malignancy of the head and
      neck incidence rate was significantly lower in patients with high-grade
      oropharyngeal cancer from 2000 to 2008 (30.3 vs 65.5 and 54.6 from 1973-1989 and
      1990-1999, respectively; p < .001). CONCLUSION: The incidence of second primary
      malignancy of the head and neck in patients with head and neck cancer has
      decreased over time. This is driven by lower rates in patients with high-grade
      oropharyngeal cancer, is temporally related with increases in HPV-associated
      oropharyngeal cancer, and suggests that incidence rates of second primary
      malignancy of the head and neck may be lower for HPV-associated cancer. (c) 2015
      Wiley Periodicals, Inc. Head Neck 38: E873-E883, 2016.

PMID- 25966423
TI  - Epidemiology of cholangiocarcinoma.
AB  - Cholangiocarcinoma (CCA) is a cancer arising from the intra- or extrahepatic bile
      ducts and mainly characterized by its late diagnosis and fatal outcome. CCA is
      the second most common primary liver tumour and accounts for approximately 10-15%
      of all hepatobiliary malignancies. The development of CCA is linked to a wide
      spectrum of conditions causing biliary inflammation, cholestasis and inflammation
      of the liver. The geographic diversity of risk factors is reflected in
      considerable differences in incidence worldwide. Although data are not
      consistent, incidence seems to be rising in the Western World. Given the limited
      opportunities of treating advanced CCA, surveillance has been suggested as a
      strategy for detection of early disease in the high-risk group of patients with
      primary sclerosing cholangitis (PSC). In this review we present an updated
      overview of the epidemiology of CCA. We also highlight the risk of CCA in PSC
      with special focus on surveillance strategies. 

PMID- 25966424
TI  - Pathogenesis of cholangiocarcinoma: From genetics to signalling pathways.
AB  - Cholangiocarcinoma (CCA) is a malignant tumour of bile duct epithelial cells with
      dismal prognosis and rising incidence. Chronic inflammation resulting from liver
      fluke infection, hepatitis and other inflammatory bowel diseases is a major
      contributing factor to cholangiocarcinogenesis, likely through accumulation of
      serial genetic and epigenetic alterations resulting in aberration of oncogenes
      and tumour suppressors. Recent studies making use of advances in high-throughput
      genomics have revealed the genetic landscape of CCA, greatly increasing our
      understanding of its underlying biology. A series of highly recurrent mutations
      in genes such as TP53, KRAS, SMAD4, BRAF, MLL3, ARID1A, PBRM1 and BAP1, which are
      known to be involved in cell cycle control, cell signalling pathways and
      chromatin dynamics, have led to investigations of their roles, through molecular
      to mouse modelling studies, in cholangiocarcinogenesis. This review focuses on
      the landscape genetic alterations in CCA and its functional relevance to the
      formation and progression of CCA. 

PMID- 25966425
TI  - Clinical presentation, risk factors and staging systems of cholangiocarcinoma.
AB  - Cholangiocarcinoma (CCA) is the second most common primary liver tumour. Intra
      hepatic CCA develops within the liver parenchyma while extrahepatic CCA involves
      the biliary tree within the hepatoduodenal ligament. Hilar CCA are also called
      Klatskin tumour. The CCA incidence has increased worldwide over the last years,
      but there are also geographic differences, with focus in Asian countries. Known
      risk factors are primary sclerosing cholangitis (PSC), hepatolithiasis, Caroli's
      disease, hepatitis B and C infection, liver flukes, cirrhosis, diabetes, obesity,
      alcohol consumption and probably tobacco smoking. Patients with early CCA have
      only little discomfort, but can later show episodes with jaundice and other non
      specific tumour symptoms. For the staging of the disease different
      classifications are available, which consider various factors like tumour size,
      location, regional lymph nodes, metastasis, vascular involvement and tumour
      marker.

PMID- 25966426
TI  - Radiological diagnosis in cholangiocarcinoma: Application of computed tomography,
      magnetic resonance imaging, and positron emission tomography.
AB  - The purpose of radiological imaging in patients with suspected or known
      cholangiocarcinoma (CCA) is tumour detection, lesion characterization and
      assessment of resectability. Different imaging modalities are implemented
      complementary in the diagnostic work-up. Non-invasive imaging should be performed
      prior to invasive biliary procedures in order to avoid false positive results.
      For assessment of intraparenchymal tumour extension and evaluation of biliary and
      vascular invasion, MRI including MRCP and CT are the primarily used imaging
      modalities. The role of PET remains controversial with few studies showing
      benefit with the detection of unexpected metastatic spread, the differentiation
      between benign and malignant biliary strictures, and for discriminating post
      therapeutic changes and recurrent CCA. 

PMID- 25966427
TI  - Endoscopic diagnosis of cholangiocarcinoma: From endoscopic retrograde
      cholangiography to bile proteomics.
AB  - Cholangiocarcinoma (CCA) is the second most common primary liver cancer. In
      clinical practice, the diagnosis remains challenging and often requires
      endoscopic approaches. Endoscopic retrograde and percutaneous transhepatic
      cholangiography are the first-line endoscopic procedures for the evaluation of
      indeterminate bile duct strictures. Tissue acquisition via brush cytology and
      forceps biopsies allows the cytological and/or histological confirmation of the
      disease. Due to the low sensitivity of these techniques, repetitive examinations
      and/or alternative approaches are required. Cholangioscopy, endoscopic and
      intraductal ultrasound and confocal laser endomicroscopy are additional methods
      which can be applied for the diagnosis of CCA. Particularly, new experimental
      approaches like bile and urine proteomic analyses show promising results which
      have to be evaluated prospectively for further integration in diagnostic
      algorithms.

PMID- 25966428
TI  - Pathologic classification of cholangiocarcinoma: New concepts.
AB  - Herein, we propose a new pathologic classification of cholangiocarcinoma (CCA)
      based on recent progress in studies of preinvasive CCA lesions and the
      relationship of CCA to hepatic progenitor cells, as well as a new concept with
      respect to the pathologic similarities between biliary and pancreatic neoplasms.
      Depending on anatomical location, CCA is classifiable as intrahepatic (iCCA),
      perihilar (pCCA), and distal CCA (dCCA). iCCA is classifiable as the conventional
      type and the bile ductular type, whereas pCCA and dCCA mainly present as
      conventional adenocarcinoma. In addition, these three CCAs may present as the
      intraductal neoplasm type or rare variants. Bile ductular CCA resembles
      proliferating bile ductules and expressing hepatic progenitor cell phenotypes.
      Four types of preinvasive lesions are proposed: flat, papillary, tubular lesion,
      and cystic lesion. These lesions are eventually followed by invasive CCA.
      Interestingly, these preinvasive lesions have pancreatic counterparts. This CCA
      classification may introduce a new field of CCA research.

PMID- 25966429
TI  - Role of surgery in cholangiocarcinoma: From resection to transplantation.
AB  - The treatment of cholangiocarcinoma (CCA) represents a major challenge to modern
      medicine. Diagnostics and treatment modalities are complex and require close
      interdisciplinary work-up. However, surgical resection currently offers the only
      potentially curative treatment option. Improved peri-operative strategies as well
      as optimized surgical techniques have generated significantly increased survival
      chances for patients in recent years. Complete tumor resection is the key
      parameter to long-term survival. In spite of expanded surgical limits R0
      resection cannot be achieved in some cases as parenchymal disease may limit the
      extent of resection. Although liver transplantation (LT) is not a standard
      therapy for CCA today, it may be an option in such selected cases. Protocols
      including neo-adjuvant radio-chemotherapy and staging-lymphadenectomy before LT
      have generated impressive results in the recent past. Since palliative options
      generate only short-term survival extension LT for CCA has lately been discussed
      more extensively after the procedure had been abandoned due to dismal survival
      data in the 1990-years. This review offers a comprehensive picture of the current
      surgical treatment option for cholangiocarcinoma.

PMID- 25966430
TI  - Role of photodynamic therapy and intraductal radiofrequency ablation in
      cholangiocarcinoma.
AB  - Cholangiocarcinoma comprises 3% of all gastrointestinal malignancies. Prognosis
      is poor as the disease is locally advanced at the time of its presentation.
      Biliary endoprosthesis are widely used for biliary decompression, however, they
      only provides temporary relief. Photodynamic therapy and Radiofrequency ablation
      are two innovative approaches performed endoscopically to locally destruct the
      malignant tissue. This chapter focuses on their application and appropriate use
      along with their benefits and complications. 

PMID- 25966431
TI  - Integration of chemoembolization and radioembolization into multimodal treatment
      of cholangiocarcinoma.
AB  - Over the last decade radioembolization and transarterial chemoembolization have
      been shown to be effective in unresectable intrahepatic cholangiocellular
      carcinoma. Unfortunately, up to now the evidence is not high with most of the
      conclusions drawn from single center retrospective analyses with small sample
      sizes treated in the salvage situation. However, the results are promising and
      suggest a survival benefit in the treatment of unresectable cholangiocellular
      carcinoma, even in an advanced stage with extrahepatic disease. In the following,
      available results of the treatment of unresectable cholangiocellular carcinoma by
      radioembolization and transarterial chemoembolization will be summarized. Special
      attention will be given to prognostic factors and efficacy as measured by
      response criteria. The potential integration of these therapies into multimodal
      treatment concepts will be discussed with focus on the intensification of therapy
      and a staged concept of therapy.

PMID- 25966432
TI  - The role of adjuvant chemotherapy and radiotherapy for cholangiocarcinoma.
AB  - Cholangiocarcinomas are rare cancers arising from the epithelia of the biliary
      tract. The only prospect of curative therapy is with surgery. However, relapse
      rates are high with five-year survival rates typically around 20-30%. Involved
      resection margins and spread to local lymph nodes are associated with a higher
      risk of relapse. Such poor outcomes provide a rationale for adjuvant strategies
      to improve survival. However, there is little randomised data to support the use
      of adjuvant therapy; the available evidence base is based mostly on retrospective
      case series and results are often conflicting. This review evaluates the
      available evidence. Adjuvant therapy may be considered on an individual patient
      basis after discussion of the limitations of our knowledge. The results of
      prospective, randomised clinical trials of adjuvant therapy are eagerly awaited.
      Progress will require collaboration of basic science and clinical oncology and
      the execution of well-designed clinical trials. 

PMID- 25966433
TI  - Systemic therapy of cholangiocarcinoma: From chemotherapy to targeted therapies.
AB  - Cholangiocarcinomas (CCA) are rare tumors of the liver with poor prognosis. The
      standard of care in patients with unresectable tumors or metastatic disease is
      combination chemotherapy (CT) with gemcitabine and cisplatin. Targeted therapies
      inhibiting EGFR, VEGF, MEK and others are broadly tested in CCA but to date, the
      existing data from randomized and nonrandomized trials do not justify the
      application of small molecules outside of clinical trials. In clinical practice,
      many patients receive second-line CT after failure of gemcitabine/cisplatin,
      although there is so far no evidence to support second-line CT. This review
      summarizes current chemotherapy protocols and ongoing studies, including
      conventional chemotherapy and targeted therapies.

PMID- 25966434
TI  - Future directions in the treatment of cholangiocarcinoma.
AB  - Cholangiocarcinoma (CCA) comprises a heterogeneous group of cancers with
      pathologic features of biliary tract differentiation, and is best classified
      anatomically as intrahepatic CCA (ICC), perihilar (pCCA), or distal (dCCA) CCA.
      They represent a clinically and genetically diverse collection of cancers.
      Surgical resection represents the only curative modality for CCA, although there
      are encouraging data with liver transplantation for early stage pCCA. There is no
      established adjuvant therapy for CCA. Unfortunately, most patients with CCA will
      present with unresectable or metastatic disease with poor prognosis. Currently
      the combination of gemcitabine and cisplatin remains the standard therapy for
      advanced CCA. No second line therapy has definitely demonstrated improved
      survival benefits. Development of molecularly targeted therapies in advanced CCA
      remains challenging. However, recent efforts with targeted and whole exome
      sequencing have defined the landscape of mutations underlying CCA, particularly
      ICC. The identification of novel molecular signatures in CCA coupled with
      molecularly targeted therapy development provides the potential for developing
      novel therapeutic options in this intractable disease.

PMID- 25966435
TI  - Assessment of volatile and non-volatile compounds in durian wines fermented with
      four commercial non-Saccharomyces yeasts.
AB  - BACKGROUND: Chemical compositions of durian wines fermented with Metschnikowia
      pulcherrima Flavia, Torulaspora delbrueckii Biodiva, Pichia kluyveri FrootZen and
      Kluyveromyces thermotolerans Concerto were investigated. RESULTS: Sucrose was not
      utilized by M. pulcherrima and P. kluyveri, resulting in little formation of
      ethanol (0.3-0.5%, v/v), while about 7% ethanol was produced by the other two
      yeasts. Volatiles such as esters and sulfur-containing compounds were synthesized
      or catabolized and distinctive differences existed among yeasts. Larger amounts
      of higher alcohols and ethyl esters were detected in wines fermented by T.
      delbrueckii and K. thermotolerans, whereas M. pulcherrima and P. kluyveri
      produced more acetate esters such as ethyl acetate (1034.43 and 131.05 mg L(-1)
      respectively) and isoamyl acetate (0.56 and 27.68 mg L(-1) respectively). Most
      endogenous sulfur volatiles such as disulfides declined to trace levels, but new
      ones such as thioesters were formed. Sulfur volatiles in wines fermented by T.
      delbrueckii accounted for 0.20% relative peak area (RPA), followed by K.
      thermotolerans (0.23% RPA), P. kluyveri (1.43% RPA) and M. pulcherrima (4.16%
      RPA). CONCLUSION: The findings showed that a more complex flavor could result
      from fermentation with different non-Saccharomyces yeasts and the typical durian
      odor would still remain.

PMID- 25966436
TI  - Contribution of sacral neuromodulation to manage persistent voiding dysfunction
      after surgery for deep infiltrating endometriosis with colorectal involvement:
      preliminary results.
AB  - OBJECTIVE: Around 5% of women experience persistent voiding dysfunction after
      surgery for deep infiltrating endometriosis (DIE) with colorectal involvement.
      The gold standard to manage persistent voiding dysfunction is intermittent self
      catherization, but this treatment may reduce quality of life of the patients due
      to care constraints. The objective of our study was to assess the contribution of
      sacral neuromodulation (SNM) in the management of persistent voiding dysfunction
      secondary to surgery for DIE with colorectal resection. STUDY DESIGN: Five
      patients referred for persistent voiding dysfunction after surgery for DIE with
      colorectal resection were included and fitted with a temporary SNM system to test
      for feasibility. This consisted of placing an electrode unilaterally next to the
      S3 sacral nerve root and connecting it to an external pacemaker. The patients
      wore the electrode and the external neurostimulator for 21 days and kept a
      voiding diary. The SNM test was considered positive when a 50% decrease in self
      catheterization was achieved after removal of the electrode. The system was
      implanted permanently in patients with a positive SNM test. Urodynamic tests were
      performed before and after the SNM test. RESULTS: Two of the five patients had a
      positive SNM test and were implanted permanently. At 40 months the first patient
      had completely stopped self-catheterization and the second patient was performing
      self-catheterization twice a day with a post voiding residue volume of less than
      100ml at 52 months. CONCLUSION: SNM could be a curative technique in some
      patients with persistent voiding dysfunction after surgery for DIE. Further
      studies are required to better select patients who might benefit from SNM testing
      and subsequent device implantation.

PMID- 25966437
TI  - Comparison of TVT and TOT on urethral mobility and surgical outcomes in stress
      urinary incontinence with hypermobile urethra.
AB  - OBJECTIVE: To compare the change of urethral mobility after midurethral sling
      procedures in stress urinary incontinence with hypermobile urethra and assess
      these findings with surgical outcomes. STUDY DESIGN: 141 women who agreed to
      undergo midurethral sling operations due to stress urinary incontinence with
      hypermobile urethra were enrolled in this non-randomized prospective
      observational study. Preoperatively, urethral mobility was measured by Q tip
      test. All women were asked to complete Urogenital Distress Inventory Short Form
      (UDI-6) and Incontinence Impact Questionnaire Short Form (IIQ-7) to assess the
      quality of life. Six months postoperatively, Q tip test and quality of life
      assessment were repeated. The primary surgical outcomes were classified as cure,
      improvement and failure. Transient urinary obstruction, de novo urgency, voiding
      dysfunction were secondary surgical outcomes. RESULTS: Of 141 women, 50 (35. 5%)
      women underwent TOT, 91 (64.5%) underwent TVT. In both TOT and TVT groups,
      postoperative Q tip test values, IIQ-7 and UDI-6 scores were statistically
      reduced when compared with preoperative values. Postoperative Q tip test value in
      TVT group was significantly smaller than in TOT group [25 degrees (15-45 degrees
      ) and 20 degrees  (15-45 degrees ), respectively]. When we compared the Q-tip
      test value, IIQ-7 and UDI-6 scores changes, there were no statistically
      significant changes between the groups. Postoperative urethral mobility was more
      frequent in TOT group than in TVT group (40% vs 23.1%, respectively).
      Postoperative primary and secondary outcomes were similar in both groups.
      CONCLUSIONS: Although midurethral slings decrease the urethtal hypermobility,
      postoperative mobility status of urethra does not effect surgical outcomes of
      midurethral slings in women with preoperative urethral hypermobility.

PMID- 25966438
TI  - Aortic arch atherosclerosis in patients with severe aortic stenosis can be argued
      by greater day-by-day blood pressure variability.
AB  - BACKGROUND AND PURPOSE: Although it is well known that the prevalence of aortic
      arch plaques, one of the risk factors for ischemic stroke, is high in patients
      with severe aortic stenosis, the underlying mechanisms are not well understood.
      Increased day-by-day blood pressure (BP) variability is also known to be
      associated with stroke; however, little is known on the association between day
      by-bay BP variability and aortic arch atherosclerosis in patients with aortic
      stenosis. Our objective was to clarify the association between day-by-day BP
      variables (average values and variability) and aortic arch atherosclerosis in
      patients with severe aortic stenosis. METHODS: The study population consisted of
      104 consecutive patients (mean age 75 +/- 8 years) with severe aortic stenosis
      who were scheduled for aortic valve replacement. BP was measured in the morning
      in at least 4 consecutive days (mean 6.8 days) prior to the day of surgery. Large
      (>=4 mm), ulcerated, or mobile plaques were defined as complex plaques using
      transesophageal echocardiography. RESULTS: Cigarette smoking and all systolic BP
      variables were associated with the presence of complex plaques (p < 0.05),
      whereas diastolic BP variables were not. Multiple regression analysis indicated
      that day-by-day mean systolic BP and day-by-day systolic BP variability remained
      independently associated with the presence of complex plaques (p < 0.05) after
      adjustment for age, male sex, cigarette smoking, hypertension,
      hypercholesterolemia, and diabetes mellitus. CONCLUSIONS: These findings suggest
      that higher day-by-day mean systolic BP and day-by-day systolic BP variability
      are associated with complex plaques in the aortic arch and consequently stroke
      risk in patients with aortic stenosis.

PMID- 25966439
TI  - Timing of invasive strategy in NSTE-ACS patients and effect on clinical outcomes:
      A systematic review and meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Previous randomized controlled trials (RCTs) have produced
      conflicting results on the effects of early versus delayed invasive strategy in
      NSTE-ACS patients. OBJECTIVES: To perform up to date meta-analysis on the pooled
      data sample comparing early versus delayed invasive strategy, and to explore
      potential causes for the observed high statistical heterogeneity. METHODS:
      MEDLINE via Pubmed, Central, Google Scholar, Clinical Trials Registry, Current
      controlled study and ClinicalTrials.gov registry and relevant conference
      proceedings were searched. RCTs were included that directly compared early versus
      delayed invasive strategy and reported rates of death, new myocardial infarction
      (MI) and/or recurrent ischemia. RESULTS: 10 RCTs with 6089 patients were
      included. Time to coronary angiography varied from 0.5 to 24 h in the early and
      from 20.5 to 86 h in the delayed group. Meta-analysis showed no significant
      difference in mortality (OR = 0.83, 95%CI 0.64-1.08, P = 0.16), and similar new
      MI rates (OR = 1.02, 95%CI 0.63-1.64, P = 0.94). The rate of recurrent ischemia
      was reduced in patients undergoing early coronary angiography (OR = 0.56, 95%CI
      0.40-0.79, P = 0.001). Subgroup analysis indicated that the rate of new MI tended
      to depend on the study-specific endpoint definition (p for difference between
      subgroups 0.11), while a meta-regression revealed association of new MI rates
      with the within-study delay to coronary angiography (p = 0.05). CONCLUSION: Early
      invasive strategy appears to reduce the occurrence of recurrent ischemia, but
      confers no mortality benefit. The true effect on the occurrence of new MI is
      obscured by the high between-study heterogeneity that stems mainly from non
      uniform timing of early intervention and new MI definitions across the trials.

PMID- 25966440
TI  - HDL cholesterol, leptin and interleukin-6 predict high risk coronary anatomy
      assessed by CT angiography in patients with stable chest pain.
AB  - OBJECTIVES: Coronary computed tomography angiography (CTA) describes several
      features of coronary plaques, i.e. location, severity, and composition.
      Integrated CTA scores are able to identify individual patterns of higher risk. We
      sought to test whether circulating biomarkers related with metabolism and
      inflammation could predict high risk coronary anatomy at CTA in patients with
      stable chest pain. METHODS: We evaluated a panel of 17 biomarkers in 429 patients
      (60.3 +/- 0.4 years, 268 males) with stable chest pain who underwent coronary CTA
      having been enrolled in the Evaluation of Integrated Cardiac Imaging (EVINCI)
      study. The individual CTA risk score was calculated combining plaque extent,
      severity, composition, and location. The presence and distribution of non
      calcified, mixed and calcified plaques were analyzed in each patient. RESULTS:
      After adjustment for age, sex and medical treatment, high-density lipoprotein
      (HDL) cholesterol, leptin, and interleukin-6 (IL-6) were independent predictors
      of CTA risk score at multivariate analysis (P = 0.050, 0.002, and 0.007,
      respectively). Integrating these biomarkers with common clinical variables, a
      model was developed which showed a better discriminating ability than the
      Framingham Risk Score and the Euro-SCORE in identifying the patients with higher
      CTA risk score (area under the receiver-operating characteristics curve = 0.81,
      0.63 and 0.71, respectively, P < 0.001). These three biomarkers were
      significantly altered in patients with mixed or non-calcified plaques.
      CONCLUSIONS: In patients with stable chest pain, low HDL cholesterol, low leptin
      and high IL-6 are independent predictors of high risk coronary anatomy as defined
      by an integrated CTA risk score.

PMID- 25966441
TI  - Non-HDL cholesterol goal attainment and its relationship with triglyceride
      concentrations among diabetic subjects with cardiovascular disease: A nationwide
      survey of 2674 individuals in Hungary.
AB  - AIMS: Non-HDL cholesterol represents the pro-atherogenic, apo-B-containing
      lipoprotein fraction of circulating lipids, and represents a secondary target for
      CVD prevention in people with diabetes. We therefore assessed the proportion of
      individuals with diabetes and CVD who attain a non-HDL-C goal of <2.6 mmol/L, the
      extent to which triglycerides influence this goal attainment, and their
      relationship with HDL-C and triglyceride-rich lipoproteins (TRL). METHODS AND
      RESULTS: Of 2674 diabetic subjects with baseline CVD in the Hungarian MULTI-GAP
      programme (mean age 64.8 years, mean HbA1c 7.2%), an LDL-C goal <1.8 and non-HDL
      C goal <2.6 mmol/L was attained in 13.5% and 17.7% individuals, respectively. Non
      HDL-C goal attainment declined at higher triglyceride concentrations; and
      graphically this relationship appeared to be continuously and inversely
      associated with triglyceride concentrations. In contrast, the relationship
      between LDL-C goal attainment was inversely and continuously associated with
      triglyceride levels up to about 2.5 mmol/L, after which the graphical appearance
      plateaued such that no further difference in LDL-C were observed beyond
      triglyceride levels of 2.5 mmol/L. With increasing triglyceride concentrations,
      non-HDL-C increased continuously, HDL-C decreased initially but later plateaued
      (at 1.5-2.0 [men] or 2.0-2.5 mmol/L [women]), LDL-C levels plateaued at about 2.0
      2.5 mmol/L, and TRL-cholesterol (non-HDL-C minus LDL-C) rose continuously. In
      multivariable-adjusted models, elevated triglyceride concentrations, non
      specialist care and uncontrolled blood pressure were inversely associated with
      non-HDL-C goal attainment. Triglyceride levels were more strongly associated with
      non-HDL-C than with LDL-C goal attainment (ORs per 1-SD increase in log
      triglycerides was 0.74, 95% CI 0.61-0.89, for LDL-C goal attainment, and 0.49,
      95% CI 0.38-0.61, for non-HDL-C goal attainment). CONCLUSION: Non-HDL-C goal
      attainment was suboptimal in people with diabetes and co-existing CVD. This was
      most marked at higher triglyceride levels, possibly due to higher levels of TRL.

PMID- 25966442
TI  - Glutaredoxin 2a overexpression in macrophages promotes mitochondrial dysfunction
      but has little or no effect on atherogenesis in LDL-receptor null mice.
AB  - AIMS: Reactive oxygen species (ROS)-mediated formation of mixed disulfides
      between critical cysteine residues in proteins and glutathione, a process
      referred to as protein S-glutathionylation, can lead to loss of enzymatic
      activity and protein degradation. Since mitochondria are a major source of ROS
      and a number of their proteins are susceptible to protein-S-glutathionylation, we
      examined if overexpression of mitochondrial thioltranferase glutaredoxin 2a
      (Grx2a) in macrophages of dyslipidemic atherosclerosis-prone mice would prevent
      mitochondrial dysfunction and protect against atherosclerotic lesion formation.
      METHODS AND RESULTS: We generated transgenic Grx2aMac(LDLR-/-) mice, which
      overexpress Grx2a as an EGFP fusion protein under the control of the macrophage
      specific CD68 promoter. Transgenic mice and wild type siblings were fed a high
      fat diet for 14 weeks at which time we assessed mitochondrial bioenergetic
      function in peritoneal macrophages and atherosclerotic lesion formation. Flow
      cytometry and Western blot analysis demonstrated transgene expression in blood
      monocytes and peritoneal macrophages isolated from Grx2aMac(LDLR-/-) mice, and
      fluorescence confocal microscopy studies confirmed that Grx2a expression was
      restricted to the mitochondria of monocytic cells. Live-cell bioenergetic
      measurements revealed impaired mitochondrial ATP turnover in macrophages isolated
      from Grx2aMac(LDLR-/-) mice compared to macrophages isolated from non-transgenic
      mice. However, despite impaired mitochondrial function in macrophages of
      Grx2aMac(LDLR-/-) mice, we observed no significant difference in the severity of
      atherosclerosis between wildtype and Grx2aMac(LDLR-/-) mice. CONCLUSION: Our
      findings suggest that increasing Grx2a activity in macrophage mitochondria
      disrupts mitochondrial respiration and ATP production, but without affecting the
      proatherogenic potential of macrophages. Our data suggest that macrophages are
      resistant against moderate mitochondrial dysfunction and rely on alternative
      pathways for ATP synthesis to support the energetic requirements.

PMID- 25966443
TI  - Spectrum of mutations of the LPL gene identified in Italy in patients with severe
      hypertriglyceridemia.
AB  - BACKGROUND: Monogenic hypertriglyceridemia (HTG) may result from mutations in
      some genes which impair the intravascular lipolysis of triglyceride (TG)-rich
      lipoproteins mediated by the enzyme Lipoprotein lipase (LPL). Mutations in the
      LPL gene are the most frequent cause of monogenic HTG (familial chylomicronemia)
      with recessive transmission. METHODS: The LPL gene was resequenced in 149
      patients with severe HTG (TG > 10 mmol/L) and 106 patients with moderate HTG (TG
      > 4.5 and <10 mmol/L) referred to tertiary Lipid Clinics in Italy. RESULTS: In
      the group of severe HTG, 26 patients (17.4%) were homozygotes, 9 patients (6%)
      were compound heterozygotes and 15 patients (10%) were simple heterozygotes for
      rare LPL gene variants. Single or multiple episodes of pancreatitis were recorded
      in 24 (48%) of these patients. There was no difference in plasma TG concentration
      between patients with or without a positive history of pancreatitis. Among
      moderate HTG patients, six patients (5.6%) were heterozygotes for rare LPL
      variants; two of them had suffered from pancreatitis. Overall 36 rare LPL
      variants were found, 15 of which not reported previously. Systematic analysis of
      close relatives of mutation carriers led to the identification of 44 simple
      heterozygotes (plasma TG 3.2 +/- 4.1 mmol/L), none of whom had a positive history
      of pancreatitis. CONCLUSIONS: The prevalence of rare LPL variants in patients
      with severe or moderate HTG, referred to tertiary lipid clinics, was 50/149
      (33.5%) and 6/106 (5.6%), respectively. Systematic analysis of relatives of
      mutation carriers is an efficient way to identify heterozygotes who may develop
      severe HTG.

PMID- 25966444
TI  - Supramolecular amphipathicity for probing antimicrobial propensity of host
      defence peptides.
AB  - Host defence peptides (HDPs) are effector components of innate immunity that
      provide defence against pathogens. These are small-to-medium sized proteins which
      fold into amphipathic conformations toxic to microbial membranes. Here we explore
      the concept of supramolecular amphipathicity for probing antimicrobial propensity
      of HDPs using elementary HDP-like amphiphiles. Such amphiphiles are individually
      inactive, but when ordered into microscopic micellar assemblies, respond to
      membrane binding according to the orthogonal type of their primary structure. The
      study demonstrates that inducible supramolecular amphipathicity can discriminate
      against bacterial growth and colonisation thereby offering a physico-chemical
      rationale for tuneable targeting of biological membranes. 

PMID- 25966445
TI  - Levels of polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) and dioxin-like
      polychlorinated biphenyls (DL-PCBs) in breast milk in Shanghai, China: A temporal
      upward trend.
AB  - Human milk samples were collected from 150 mothers in 2011 and 2012 in Shanghai,
      China and analyzed for 17 polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) and
      12 dioxin-like polychlorinated biphenyls (DL-PCBs). The up-bound Toxic Equivalent
      Quantity (TEQ) ranged from 0.27 to 16.8 pg TEQ/g lipid (mean 5.4 pg TEQ/g lipid)
      for ?PCDD/Fs and from 0.75 to 10.2 pg TEQ/g lipid (mean 2.9 pg TEQ/g lipid) for
      ?DL-PCBs. TEQs in our study were lower than those in most countries worldwide,
      and displayed a notable uptrend, in contrast with those in China's national
      survey in 2007. TEQs in mother milks from urban areas were higher than those from
      rural areas, and an orderly distribution was found in four geographical regions:
      Eastern China>Central China~Southwestern China>Northwestern China. Levels of
      analytes in Shanghai native mothers' milk ranked the first among those from all
      provinces and cities investigated. Migrant mothers to Shanghai from other inland
      provinces could potentially represent the population for exposure and risk
      assessment in their birth and grown-up places. Both the distribution and the
      uptrend were associated with release of these pollutants due to rapid
      industrialization and urbanization in China. Fine correlations were observed
      between TEQs and age of mothers, and weak correlations between TEQs and
      consumption of meat & meat products. Participants, who preferred both fresh water
      and marine fish to freshwater fish only, were prone to be exposed to higher level
      of PCBs. The estimated daily intake (EDI) doses for breastfed neonates entirely
      exceeded the tolerable intake dose by WHO.

PMID- 25966446
TI  - Endoscopic injection of cyanoacrylate glue versus other endoscopic procedures for
      acute bleeding gastric varices in people with portal hypertension.
AB  - BACKGROUND: In people with portal hypertension, gastric varices are less
      prevalent than oesophageal varices. The risk of bleeding from gastric varices
      seems to be lower than from oesophageal varices; however, when gastric varices
      bleed, it is often severe and associated with higher mortality. Endoscopic
      sclerotherapy of bleeding gastric varices with N-butyl-2-cyanoacrylate glue
      (cyanoacrylate) is considered the best haemostasis with a lower risk of re
      bleeding compared with other endoscopic methods. However, there are some
      inconsistencies between trials regarding mortality, incidence of re-bleeding, and
      adverse effects. OBJECTIVES: To assess the benefits and harms of sclerotherapy
      using cyanoacrylate compared with other endoscopic sclerotherapy procedures or
      with variceal band ligation for treating acute gastric variceal bleeding with or
      without vasoactive drugs in people with portal hypertension and to assess the
      best dosage of cyanoacrylate. SEARCH METHODS: We searched the Cochrane Hepato
      Biliary Controlled Trials Register, the Cochrane Central Register of Controlled
      Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index Expanded from
      inception to September 2014 and reference lists of articles. We included trials
      irrespective of trial setting, language, publication status, or date of
      publication. SELECTION CRITERIA: Randomised clinical trials comparing
      sclerotherapy using cyanoacrylate versus other endoscopic methods (sclerotherapy
      using alcohol-based compounds or endoscopy band ligation) for acute gastric
      variceal bleeding in people with portal hypertension. DATA COLLECTION AND
      ANALYSIS: We performed the review following the recommendations of the Cochrane
      Handbook for Systematic Reviews of Interventions and the Cochrane Hepato-Biliary
      Module.We presented results as risk ratios (RR) with 95% confidence intervals
      (CI), with I(2) statistic values as a measure of intertrial heterogeneity. We
      analysed data with both fixed-effect and random-effects models, and reported the
      results with random-effects models. We performed subgroup, sensitivity, and trial
      sequential analyses to evaluate the robustness of the overall results, risk of
      bias, sources of intertrial heterogeneity, and risk of random errors. MAIN
      RESULTS: We included six randomised clinical trials with three different
      comparisons: one trial compared two different doses of cyanoacrylate in 91
      adults, bleeding actively from all types of gastric varices; one trial compared
      cyanoacrylate versus alcohol-based compounds in 37 adults with active or acute
      bleeding from isolated gastric varices only; and four trials compared
      cyanoacrylate versus endoscopic band ligation in 365 adults, with active or acute
      bleeding from all types of gastric varices. Main outcomes in the included trials
      were bleeding-related mortality, failure of intervention, re-bleeding, adverse
      events, and control of bleeding. Follow-up varied from six to 26 months. The
      participants included in these trials had chronic liver disease of different
      severities, were predominantly men, and most were from Eastern countries. We
      judged all trials at high risk of bias. Application of quality criteria for all
      outcomes yielded very low quality grade of the evidence in the three analyses,
      except for the low quality evidence rated for the re-bleeding outcome in the
      cyanoacrylate versus endoscopic band ligation comparison. Two different doses of
      cyanoacrylate: we found very low quality evidence from one trial for the effect
      of 0.5 mL compared with 1.0 mL of cyanoacrylate on all-cause mortality (20/44
      (45.5%) with 0.5 mL versus 21/47 (45%) with 1.0 mL; RR 1.02; 95% CI 0.65 to
      1.60), 30-day mortality (RR 1.07; 95% CI 0.41 to 2.80), failure of intervention
      (RR 1.07; 95% CI 0.56 to 2.05), prevention of re-bleeding (RR 1.30; 95% CI 0.73
      to 2.31), adverse events reported as fever (RR 0.56; 95% CI 0.32 to 0.98), and
      control of bleeding (RR 1.04; 95% CI 0.78 to 1.38). Cyanoacrylate versus alcohol
      based compounds: we found very low quality evidence from one trial for the effect
      of cyanoacrylate versus alcohol-based compounds on 30-day mortality (2/20 (10%)
      with cyanoacrylate versus 4/17 (23.5%) with alcohol-based compound; RR 0.43; 95%
      CI 0.09 to 2.04), failure of intervention (RR 0.36; 95% CI 0.09 to 1.35),
      prevention of re-bleeding (RR 0.85; 95% CI 0.30 to 2.45), adverse events reported
      as fever (RR 0.43; 95% CI 0.22 to 0.80), and control of bleeding (RR 1.79; 95% CI
      1.13 to 2.84). Cyanoacrylate versus endoscopic band ligation: we found very low
      quality evidence for the effect of cyanoacrylate versus endoscopic band ligation
      on bleeding-related mortality (44/185 (23.7%) with cyanoacrylate versus 50/181
      (27.6%) with endoscopic band ligation; RR 0.83; 95% CI 0.52 to 1.31), failure of
      intervention (RR 1.13; 95% CI 0.23 to 5.69), complications (RR 2.81; 95% CI 0.69
      to 11.49), and control of bleeding (RR 1.07; 95% CI 0.90 to 1.27). There was low
      quality evidence for the prevention of re-bleeding (RR 0.60; 95% CI 0.41 to
      0.88). Trial sequential analysis showed that the analyses were underpowered
      (diversity-adjusted required information size was 5290 participants for bleeding
      related mortality). AUTHORS' CONCLUSIONS: This review suggests that endoscopic
      sclerotherapy using cyanoacrylate may be more effective than endoscopic band
      ligation in terms of preventing re-bleeding from gastric varices. However, due to
      the very low quality of the evidence, we are very uncertain about our estimates
      on all-cause and bleeding-related mortality, failure of intervention, adverse
      events, and control of bleeding. The trials were at high risk of bias; the number
      of the included randomised clinical trials and number of participants included in
      each trial was small; and there was evidence of internal heterogeneity across
      trials, indirectness of evidence in terms of population, and possible publication
      bias.The effectiveness of different doses of cyanoacrylate and the comparison of
      cyanoacrylate versus alcohol compounds to treat variceal bleeding in people with
      portal hypertension is uncertain due to the very low quality of the evidence.The
      shortcomings mentioned call for more evidence from larger trials that need to be
      conducted according to the SPIRIT statement and reported according to CONSORT
      guidelines.

PMID- 25966448
TI  - Quantum controlled-phase-flip gate between a flying optical photon and a Rydberg
      atomic ensemble.
AB  - Quantum controlled-phase-flip (CPF) gate between a flying photon qubit and a
      stationary atomic qubit could allow the linking of distant computational nodes in
      a quantum network. Here we present a scheme to realize quantum CPF gate between a
      flying optical photon and an atomic ensemble based on cavity input-output process
      and Rydberg blockade. When a flying single-photon pulse is reflected off the
      cavity containing a Rydberg atomic ensemble, the dark resonance and Rydberg
      blockade induce a conditional phase shift for the photon pulse, thus we can
      achieve the CPF gate between the photon and the atomic ensemble. Assisted by
      Rydberg blockade interaction, our scheme works in the N-atoms strong-coupling
      regime and significantly relaxes the requirement of strong coupling of single
      atom to photon in the optical cavity. 

PMID- 25966449
TI  - [Not Available].

PMID- 25966450
TI  - A universal model for the evolution of viviparity? (Comment on DOI
      10.1002/bies.201400200).

PMID- 25966451
TI  - [Web 2.0: a scenario for innovation and nursing visibility].

PMID- 25966452
TI  - Health and agricultural productivity: Evidence from Zambia.
AB  - We evaluate the productivity effects of investment in preventive health
      technology through a randomized controlled trial in rural Zambia. In the
      experiment, access to subsidized bed nets was randomly assigned at the community
      level; 516 farmers were followed over a one-year farming period. We find large
      positive effects of preventative health investment on productivity: among farmers
      provided with access to free nets, harvest value increased by US$ 76,
      corresponding to about 14.7% of the average output value. While only limited
      information was collected on farming inputs, shifts in the extensive and the
      intensive margins of labor supply appear to be the most likely mechanism
      underlying the productivity improvements observed. 

PMID- 25966453
TI  - Welfare implications of learning through solicitation versus diversification in
      health care.
AB  - Using Roy's model of sorting behavior, I study welfare implications of learning
      about medical care quality through the current health care data production
      infrastructure that relies on solicitation of research subjects. Due to severe
      adverse-selection issues, I show that such learning could be biased and welfare
      decreasing. Direct diversification of treatment receipt may solve these issues
      but is infeasible. Unifying Manski's work on diversified treatment choice under
      ambiguity and Heckman's work on estimating heterogeneous treatment effects, I
      propose a new infrastructure based on temporary diversification of access that
      resolves the prior issues and can identify nuanced effect heterogeneity. 

PMID- 25966454
TI  - Application of Additive Manufacturing in Oral and Maxillofacial Surgery.
AB  - Additive manufacturing is the process of joining materials to create objects from
      digital 3-dimensional (3D) model data, which is a promising technology in oral
      and maxillofacial surgery. The management of lost craniofacial tissues owing to
      congenital abnormalities, trauma, or cancer treatment poses a challenge to oral
      and maxillofacial surgeons. Many strategies have been proposed for the management
      of such defects, but autogenous bone grafts remain the gold standard for
      reconstructive bone surgery. Nevertheless, cell-based treatments using adipose
      stem cells combined with osteoconductive biomaterials or scaffolds have become a
      promising alternative to autogenous bone grafts. Such treatment protocols often
      require customized 3D scaffolds that fulfill functional and esthetic
      requirements, provide adequate blood supply, and meet the load-bearing
      requirements of the head. Currently, such customized 3D scaffolds are being
      manufactured using additive manufacturing technology. In this review, 2 of the
      current and emerging modalities for reconstruction of oral and maxillofacial bone
      defects are highlighted and discussed, namely human maxillary sinus floor
      elevation as a valid model to test bone tissue-engineering approaches enabling
      the application of 1-step surgical procedures and seeding of Good Manufacturing
      Practice-level adipose stem cells on computer-aided manufactured scaffolds to
      reconstruct large bone defects in a 2-step surgical procedure, in which cells are
      expanded ex vivo and seeded on resorbable scaffolds before implantation.
      Furthermore, imaging-guided tissue-engineering technologies to predetermine the
      surgical location and to facilitate the manufacturing of custom-made implants
      that meet the specific patient's demands are discussed. The potential of tissue
      engineered constructs designed for the repair of large oral and maxillofacial
      bone defects in load-bearing situations in a 1-step surgical procedure combining
      these 2 innovative approaches is particularly emphasized. 

PMID- 25966455
TI  - Outdoor dissolution of detonation residues of three insensitive munitions (IM)
      formulations.
AB  - We seek to understand the environmental fate of three new insensitive munitions,
      explosive formulations developed to reduce the incidence of unintended
      detonations. To this end, we measured the size distribution of residues from low
      order detonations of IMX 101, IMX 104, and PAX 21-filled munitions and are
      studying how these three formulations weather and dissolve outdoors. The largest
      pieces collected from the detonations were centimeter-sized and we studied 12 of
      these in the outdoors test. We found that the particles break easily and that the
      dissolution of 2,4-dinitroanisole (DNAN) is quasi-linear as a function of water
      volume. DNAN is the matrix and the least soluble major constituent of the three
      formulations. We used DNAN's linear dissolution rate to estimate the life span of
      the pieces. Particles ranging in mass from 0.3 to 3.5 g will completely dissolve
      in 3-21 years given 100 cm y(-1) precipitation rates.

PMID- 25966456
TI  - Source apportionment of PAHs in surface sediments using positive matrix
      factorization combined with GIS for the estuarine area of the Yangtze River,
      China.
AB  - This study used PMF and geostatistics to quantify sources of PAHs based on 30
      samples tested for 16 PAHs in surface sediment from the Yangtze River Estuary
      (YRE) in February 2011. The results demonstrated that the total PAH
      concentrations varied from 65.07 to 954.52 ng g(-1) with a mean value of 224.00
      ng g(-1). In the inner estuary, the mean of the total PAH concentrations was
      229.89 ng g(-1), and the high molecular weight of four-to-six-ring PAHs accounted
      for 51.83% of PAHs. In the adjacent East Sea, the mean value was 218.85 ng g(-1)
      and the high molecular weight PAHs accounted for approximately 54% of total PAHs.
      A three-factor modeling result from PMF provided the most satisfactory analysis
      of PAH sources. Coke plant emissions and biomass combustion, which contributed
      45.64% of the pollution, were the most important sources, and pollutants from
      these sources were primarily concentrated in the southern branch of the estuary.
      Gasoline fuel combustion accounted for approximately 40% of the pollution, and
      the major contaminated area was in the northern region. Petrogenic sources
      (14.70%) also influenced the estuary, especially in the northeastern region.
      Water currents and source locations affected the impacted regions of PMF factors;
      the surrounding natural and artificial influences were also considered.

PMID- 25966457
TI  - Molecular dynamics simulations of structural transformation of perfluorooctane
      sulfonate (PFOS) at water/rutile interfaces.
AB  - Concentration and salinity conditions are the dominant environmental factors
      affecting the behavior of perfluorinated compounds (PFCs) on the surfaces of a
      variety of solid matrices (suspended particles, sediments, and natural minerals).
      However, the mechanism has not yet been examined at molecular scales. Here, the
      structural transformation of perfluorooctane sulfonate (PFOS) at water/rutile
      interfaces induced by changes of the concentration level of PFOS and salt
      condition was investigated using molecular dynamics (MD) simulations. At low and
      intermediate concentrations all PFOS molecules directly interacted with the
      rutile (110) surface mainly by the sulfonate headgroups through electrostatic
      attraction, yielding a typical monolayer structure. As the concentration of PFOS
      increased, the molecules aggregated in a complex multi-layered structure, where
      an irregular assembling configuration was adsorbed on the monolayer structure by
      the van der Waals interactions between the perfluoroalkyl chains. When adding
      CaCl2 to the system, the multi-layered structure changed to a monolayer again,
      indicating that the addition of CaCl2 enhanced the critical concentration value
      to yield PFOS multilayer assemblies. The divalent Ca(2+) substituted for
      monovalent K(+) as the bridging counterion in PFOS adsorption. MD simulation may
      trigger wide applications in study of perfluorinated compounds (PFCs) from
      atomic/molecular scale. 

PMID- 25966458
TI  - Disposal of historically contaminated soil in the cement industry and the
      evaluation of environmental performance.
AB  - Approximately 400000t of DDTs/HCHs-contaminated soil (CS) needed to be co
      processed in a cement kiln with a time limitation of 2y. A new pre-processing
      facility with a "drying, grinding and DDTs/HCHs vaporizing" ability was equipped
      to meet the technical requirements for processing cement raw meal and the
      environmental standards for stack emissions. And the bottom of the precalciner
      with high temperatures >1000 degrees C was chosen as the CS feeding point for co
      processing, which has rarely been reported. To assess the environmental
      performance of CS pre- and co-processing technologies, according to the local
      regulation, a test burn was performed by independent and accredited institutes
      systematically for determination of the clinker quality, kiln stack gas emissions
      and destruction efficiency of the pollutant. The results demonstrated that the
      clinker was of high quality and not adversely affected by CS co-processing. Stack
      emissions were all below the limits set by Chinese standards. Particularly,
      PCDD/PCDF emissions ranged from 0.0023 to 0.0085ngI-TEQNm(-3). The less toxic
      OCDD was the peak congener for CS co-processing procedure, while the most toxic
      congeners (i.e. 2,3,7,8-TeCDD, 1,2,3,7,8-PeCDD and 2,3,4,7,8-PeCDD) remained in a
      minor proportion. Destruction and removal efficiency (DRE) and destruction
      efficiency (DE) of the kiln system were better than 99.9999% and 99.99%,
      respectively, at the highest CS feeding rate during normal production. To
      guarantee the environmental performance of the system the quarterly stack gas
      emission was also monitored during the whole period. And all of the results can
      meet the national standards requirements. 

PMID- 25966459
TI  - Adsorption of cadmium by biochar derived from municipal sewage sludge: Impact
      factors and adsorption mechanism.
AB  - Static equilibrium experiments were carried out to investigate the impact factors
      and the mechanism of cadmium adsorption on biochar derived from municipal sewage
      sludge. An appropriate dosage of biochar is sufficient; in the experiment, 0.2%
      is the optimal dosage for the largest removal capacity, while the removal
      capacity of biochar reduces with the increasing dosage. pH is another dominant
      factor of the adsorption process. The removal capacity of biochar is lower than
      20 mg.g(-1) when the solution initial pH is lower than 2 pH units, comparatively
      retaining more than 40 mg.g(-1) at the solution initial pH higher than 3 pH
      units. Temperature has weak influence on the adsorptive performance. The main
      mechanism of the adsorption process of biochar for cadmium mainly involves (1)
      surface precipitation by forming insoluble cadmium compounds in alkaline
      condition, and (2) ion exchange for cadmium with exchangeable cations in the
      biochar, such as calcium ions.

PMID- 25966460
TI  - Iron assimilation by the clam Laternula elliptica: Do stable isotopes (delta56Fe)
      help to decipher the sources?
AB  - Iron stable isotope signatures (delta(56)Fe) in hemolymph (bivalve blood) of the
      Antarctic bivalve Laternula elliptica were analyzed by Multiple Collector
      Inductively Coupled Plasma-Mass Spectrometry (MC-ICP-MS) to test whether the
      isotopic fingerprint can be tracked back to the predominant sources of the
      assimilated Fe. An earlier investigation of Fe concentrations in L. elliptica
      hemolymph suggested that an assimilation of reactive and bioavailable Fe
      (oxyhydr)oxide particles (i.e. ferrihydrite), precipitated from pore water Fe
      around the benthic boundary, is responsible for the high Fe concentration in L.
      elliptica (Poigner et al., 2013 b). At two stations in Potter Cove (King George
      Island, Antarctica) bivalve hemolymph showed mean delta(56)Fe values of -1.19 +/-
      0.340/00 and -1.04 +/- 0.39 0/00, respectively, which is between 0.50/00 and
      0.850/00 lighter than the pool of easily reducible Fe (oxyhydr)oxides of the
      surface sediments (-0.30/00 to -0.60/00). This is in agreement with the
      enrichment of lighter Fe isotopes at higher trophic levels, resulting from the
      preferential assimilation of light isotopes from nutrition. Nevertheless,
      delta(56)Fe hemolymph values from both stations showed a high variability,
      ranging between -0.210/00 (value close to unaltered/primary Fe(oxyhydr)oxide
      minerals) and -1.910/00 (typical for pore water Fe or diagenetic Fe
      precipitates), which we interpret as a "mixed" delta(56)Fe signature caused by Fe
      assimilation from different sources with varying Fe contents and delta(56)Fe
      values. Furthermore, mass dependent Fe fractionation related to physiological
      processes within the bivalve cannot be ruled out. This is the first study
      addressing the potential of Fe isotopes for tracing back food sources of
      bivalves.

PMID- 25966462
TI  - Enhancing the speed of morpholino-DNA biosensor by electrokinetic concentration
      of DNA in a microfluidic chip.
AB  - Electrokinetic methods that conveniently concentrate charged analytes by orders
      of magnitude are highly attractive for nucleic acid assays where they can bypass
      the complexity and costs of enzyme-based amplification. The present study
      demonstrates an electrokinetic concentration device incorporating charge-neutral
      morpholino (MO) probes: as DNA analyte is concentrated in a microfluidic channel
      using ion concentration polarization (ICP) it is simultaneously hybridized to
      spots of complementary MO probes immobilized on the channel floor. This approach
      is uniquely favored by the match between the optimum buffer ionic strength of
      approximately 10mM for both MO-DNA surface hybridization and electrokinetic
      concentration. The simple and easily scalable poly(dimethylsiloxane) (PDMS)
      microfluidic device was fabricated using soft lithography and contact printing of
      a conductive polymer, poly(3,4-ethylenedioxythiophene)-polystyrene sulfonate (
      PEDOT: PSS) as a cation-selective membrane material. Using the microfluidic
      concentrator, we could increase the concentration of DNA by three orders of
      magnitude in less than 5 min at an electric field of 75 Vcm(-1). The 1000-fold
      increase in concentration of DNA led to an increase in the speed of MO-DNA
      hybridization by two orders of magnitude and enabled a detection sensitivity of
      ~1 nM within 15 min of concentration. Using the proposed microfluidic
      concentrator, we also demonstrated a rapid hybridization with a binary DNA
      mixture, containing a fully complementary and a non-complementary sequence to
      mimic molecular backgrounds present in real DNA samples.

PMID- 25966461
TI  - The Structure of an NDR/LATS Kinase-Mob Complex Reveals a Novel Kinase
      Coactivator System and Substrate Docking Mechanism.
AB  - Eukaryotic cells commonly use protein kinases in signaling systems that relay
      information and control a wide range of processes. These enzymes have a
      fundamentally similar structure, but achieve functional diversity through
      variable regions that determine how the catalytic core is activated and recruited
      to phosphorylation targets. "Hippo" pathways are ancient protein kinase signaling
      systems that control cell proliferation and morphogenesis; the NDR/LATS family
      protein kinases, which associate with "Mob" coactivator proteins, are central but
      incompletely understood components of these pathways. Here we describe the
      crystal structure of budding yeast Cbk1-Mob2, to our knowledge the first of an
      NDR/LATS kinase-Mob complex. It shows a novel coactivator-organized activation
      region that may be unique to NDR/LATS kinases, in which a key regulatory motif
      apparently shifts from an inactive binding mode to an active one upon
      phosphorylation. We also provide a structural basis for a substrate docking
      mechanism previously unknown in AGC family kinases, and show that docking
      interaction provides robustness to Cbk1's regulation of its two known in vivo
      substrates. Co-evolution of docking motifs and phosphorylation consensus sites
      strongly indicates that a protein is an in vivo regulatory target of this hippo
      pathway, and predicts a new group of high-confidence Cbk1 substrates that
      function at sites of cytokinesis and cell growth. Moreover, docking peptides
      arise in unstructured regions of proteins that are probably already kinase
      substrates, suggesting a broad sequential model for adaptive acquisition of
      kinase docking in rapidly evolving intrinsically disordered polypeptides. 

PMID- 25966463
TI  - Fluorescent detection of Hg2+ and Pb2+ using GeneFinderTM and an integrated
      functional nucleic acid.
AB  - This paper reports a simple fluorescent assay for the determination of Hg(2+) and
      Pb(2+) by using a DNA intercalator GeneFinderTM (GF) and an integrated functional
      nucleic acid (FNA). In the absence of Hg(2+) and Pb(2+), GF intercalated with the
      FNA and released moderate strong fluorescence. While in the presence of Hg(2+) or
      Pb(2+), the FNA would be induced to form T-Hg(2+)-T or G-quadruplex structure,
      interacted with which the GF would exhibit extremely strong or very weak
      fluorescence. By monitoring the fluorescence changes upon addition of these two
      ions, the Hg(2+) and Pb(2+) could be selectively detected as low as 3.23 ppb and
      2.62 ppb. As the main advantage of this assay is simplicity and the feasibility
      was demonstrated by detecting Hg(2+) and Pb(2+) in spiked water samples, this
      assay holds great potential for the development of a cost effective and useful
      tool for environmental monitoring.

PMID- 25966464
TI  - A polyaniline based ultrasensitive potentiometric immunosensor for cardiac
      troponin complex detection.
AB  - An ultrasensitive immunosensor based on potentiometric ELISA for the detection of
      a cardiac biomarker, troponin I-T-C (Tn I-T-C) complex, was developed. The sensor
      fabrication involves typical sandwich ELISA procedures, while the final signal
      readout was achieved using open circuit potentiometry (OCP). Glassy carbon (GC)
      working electrodes were first coated with emulsion-polymerized
      polyaniline/dinonylnaphthalenesulfonic acid (PANI/DNNSA) and the coated surface
      was utilized as a transducer layer on which sandwich ELISA incubation steps were
      performed. An enzymatic reaction between o-phenylenediamine (OPD) and hydrogen
      peroxide (H2O2) was catalyzed by horseradish peroxidase (HRP) labeled on the
      secondary antibodies. The polymer transducer charged state was mediated through
      electron (e(-)) and charge transfers between the transducer and charged species
      generated by the same enzymatic reaction. Such a change in the polymer transducer
      led to potential variations against an Ag/AgCl reference electrode as a function
      of Tn I-T-C complex concentration during incubations. The sequence of OPD and
      H2O2 additions, electrochemical properties of the PANI/DNNSA layer and non
      specific binding prevention were all crucial factors for the assay performance.
      Under optimized conditions, the assay has a low limit of detection (LOD) (< 5
      pg/mL or 56 fM), a wide dynamic range (> 6 orders of magnitude), high
      repeatability (coefficient of variance < 8% for all concentrations higher than 5
      pg/mL) and a short detection time (< 10 min).

PMID- 25966465
TI  - Evaluation of the swelling behaviour of iota-carrageenan in monolithic matrix
      tablets.
AB  - The swelling properties of monolithic matrix tablets containing iota-carrageenan
      were studied at different pH values, with measurements of the swelling force and
      characterization of the profile of the swelling curve. The swelling force meter
      was linked to a PC by an RS232 cable and the measured data were evaluated with
      self-developed software. The monitor displayed the swelling force vs. time curve
      with the important parameters, which could be fitted with an Analysis menu. In
      the case of iota-carrageenan matrix tablets, it was concluded that the pH and the
      pressure did not influence the swelling process, and the first section of the
      swelling curve could be fitted by the Korsmeyer-Peppas equation. 

PMID- 25966466
TI  - Towards simultaneous individual and tissue identification: A proof-of-principle
      study on parallel sequencing of STRs, amelogenin, and mRNAs with the Ion Torrent
      PGM.
AB  - DNA-based individual identification and RNA-based tissue identification represent
      two commonly-used tools in forensic investigation, aiming to identify crime scene
      sample donors and helping to provide links between DNA-identified sample donors
      and criminal acts. Currently however, both analyses are typically performed
      separately. In this proof-of-principle study, we developed an approach for the
      simultaneous analysis of forensic STRs, amelogenin, and forensic mRNAs based on
      parallel targeted DNA/RNA sequencing using the Ion Torrent Personal Genome
      Machine((r)) (PGMTM) System coupled with the AmpliSeqTM targeted amplification.
      We demonstrated that 9 autosomal STRs commonly used for individual identification
      (CSF1PO, D16S539, D3S1358, D5S818, D7S820, D8S1179, TH01, TPOX, and vWA), the
      AMELX/AMELY system widely applied for sex identification, and 12 mRNA markers
      previously established for forensic tissue identification (ALAS2 and SPTB for
      peripheral blood, MMP10 and MMP11 for menstrual blood, HTN3 and STATH for saliva,
      PRM1 and TGM4 for semen, CYP2B7P1 and MUC4 for vaginal secretion, CCL27 and LCE1C
      for skin) together with two candidate reference mRNA markers (HPRT1 and SDHA) can
      all be successfully combined. Unambiguous mRNA-based tissue identification was
      achieved in all samples from all forensically relevant tissues tested, and STR
      sequencing analysis of the tissue sample donors was 100% concordant with
      conventional STR profiling using a commercial kit. Successful STR analysis was
      obtained from 1ng of genomic DNA and mRNA analysis from 10ng total RNA; however,
      sensitivity limits were not investigated in this proof-of-principle study and are
      expected to be much lower. Since dried materials with noticeable RNA degradation
      and small DNA/RNA amplicons with high-coverage sequencing were used, the achieved
      correct individual and tissue identification demonstrates the suitability of this
      approach for analyzing degraded materials in future forensic applications.
      Overall, our study demonstrates the feasibility of simultaneously obtaining
      multilocus STR, amelogenin, and multilocus mRNA information for combined
      individual and tissue identification from a small sample of degraded biological
      material. Moreover, our study marks the first step towards combining many DNA/RNA
      markers for various forensic purposes to increase the effectiveness of molecular
      forensic analysis and to allow more forensically relevant information to be
      obtained from limited forensic material. 

PMID- 25966467
TI  - A method for human teratogen detection by geometrically confined cell
      differentiation and migration.
AB  - Unintended exposure to teratogenic compounds can lead to various birth defects;
      however current animal-based testing is limited by time, cost and high inter
      species variability. Here, we developed a human-relevant in vitro model, which
      recapitulated two cellular events characteristic of embryogenesis, to identify
      potentially teratogenic compounds. We spatially directed mesoendoderm
      differentiation, epithelial-mesenchymal transition and the ensuing cell migration
      in micropatterned human pluripotent stem cell (hPSC) colonies to collectively
      form an annular mesoendoderm pattern. Teratogens could disrupt the two cellular
      processes to alter the morphology of the mesoendoderm pattern. Image processing
      and statistical algorithms were developed to quantify and classify the compounds'
      teratogenic potential. We not only could measure dose-dependent effects but also
      correctly classify species-specific drug (Thalidomide) and false negative drug (D
      penicillamine) in the conventional mouse embryonic stem cell test. This model
      offers a scalable screening platform to mitigate the risks of teratogen exposures
      in human. 

PMID- 25966468
TI  - Robust inverse-consistent affine CT-MR registration in MRI-assisted and MRI-alone
      prostate radiation therapy.
AB  - BACKGROUND: CT-MR registration is a critical component of many radiation oncology
      protocols. In prostate external beam radiation therapy, it allows the propagation
      of MR-derived contours to reference CT images at the planning stage, and it
      enables dose mapping during dosimetry studies. The use of carefully registered CT
      MR atlases allows the estimation of patient specific electron density maps from
      MRI scans, enabling MRI-alone radiation therapy planning and treatment
      adaptation. In all cases, the precision and accuracy achieved by registration
      influences the quality of the entire process. PROBLEM: Most current registration
      algorithms do not robustly generalize and lack inverse-consistency, increasing
      the risk of human error and acting as a source of bias in studies where
      information is propagated in a particular direction, e.g. CT to MR or vice versa.
      In MRI-based treatment planning where both CT and MR scans serve as spatial
      references, inverse-consistency is critical, if under-acknowledged. PURPOSE: A
      robust, inverse-consistent, rigid/affine registration algorithm that is well
      suited to CT-MR alignment in prostate radiation therapy is presented. METHOD: The
      presented method is based on a robust block-matching optimization process that
      utilises a half-way space definition to maintain inverse-consistency. Inverse
      consistency substantially reduces the influence of the order of input images,
      simplifying analysis, and increasing robustness. An open source implementation is
      available online at http://aehrc.github.io/Mirorr/. RESULTS: Experimental results
      on a challenging 35 CT-MR pelvis dataset demonstrate that the proposed method is
      more accurate than other popular registration packages and is at least as
      accurate as the state of the art, while being more robust and having an order of
      magnitude higher inverse-consistency than competing approaches. CONCLUSION: The
      presented results demonstrate that the proposed registration algorithm is readily
      applicable to prostate radiation therapy planning.

PMID- 25966469
TI  - A Stereo Music Preprocessing Scheme for Cochlear Implant Users.
AB  - OBJECTIVE: Listening to music is still one of the more challenging aspects of
      using a cochlear implant (CI) for most users. Simple musical structures, a clear
      rhythm/beat, and lyrics that are easy to follow are among the top factors
      contributing to music appreciation for CI users. Modifying the audio mix of
      complex music potentially improves music enjoyment in CI users. METHODS: A stereo
      music preprocessing scheme is described in which vocals, drums, and bass are
      emphasized based on the representation of the harmonic and the percussive
      components in the input spectrogram, combined with the spatial allocation of
      instruments in typical stereo recordings. The scheme is assessed with
      postlingually deafened CI subjects (N = 7) using pop/rock music excerpts with
      different complexity levels. RESULTS: The scheme is capable of modifying relative
      instrument level settings, with the aim of improving music appreciation in CI
      users, and allows individual preference adjustments. The assessment with CI
      subjects confirms the preference for more emphasis on vocals, drums, and bass as
      offered by the preprocessing scheme, especially for songs with higher complexity.
      CONCLUSION: The stereo music preprocessing scheme has the potential to improve
      music enjoyment in CI users by modifying the audio mix in widespread (stereo)
      music recordings. SIGNIFICANCE: Since music enjoyment in CI users is generally
      poor, this scheme can assist the music listening experience of CI users as a
      training or rehabilitation tool.

PMID- 25966470
TI  - Accurate Segmentation of Cervical Cytoplasm and Nuclei Based on Multiscale
      Convolutional Network and Graph Partitioning.
AB  - In this paper, a multiscale convolutional network (MSCN) and graph-partitioning
      based method is proposed for accurate segmentation of cervical cytoplasm and
      nuclei. Specifically, deep learning via the MSCN is explored to extract scale
      invariant features, and then, segment regions centered at each pixel. The coarse
      segmentation is refined by an automated graph partitioning method based on the
      pretrained feature. The texture, shape, and contextual information of the target
      objects are learned to localize the appearance of distinctive boundary, which is
      also explored to generate markers to split the touching nuclei. For further
      refinement of the segmentation, a coarse-to-fine nucleus segmentation framework
      is developed. The computational complexity of the segmentation is reduced by
      using superpixel instead of raw pixels. Extensive experimental results
      demonstrate that the proposed cervical nucleus cell segmentation delivers
      promising results and outperforms existing methods. 

PMID- 25966472
TI  - Discriminative Structured Feature Engineering for Macroscale Brain Connectomes.
AB  - Neuroimaging techniques can measure structural and functional brain connectivity
      with unprecedented detail in vivo. This so-called brain connectome can be
      represented as high dimensional matrices corresponding to edge weights in graphs.
      After measuring the matrices of two cohorts (i.e., patients and healthy
      controls), one is often required to formulate computational network models for
      effective feature engineering to draw discriminative distinctions between the
      cohorts, as well as estimate the associated statistical significance. We designed
      a novel method to reveal the intrinsic features of functional matrices of
      discriminative power for group comparison. More specifically, by encouraging co
      selection of edges connected to the same node, we preserved the discriminative
      edges to maximum extent. To reduce the false positive rate of the extracted
      discriminative edges, an optimization procedure was developed to evaluate the
      significance of these edges and remove trivial ones. We validated the proposed
      method using both synthetic data and real benchmarks, and compared it to l1
      regularized logistic regression, univariate t-test and stability selection. The
      experimental results clearly showed that the proposed approach outperformed the
      three competing methods under various settings. In addition to increasing the F
      measure of feature selection, our approach captured the endogenous,
      discriminative connectivity patterns consistent with recent findings in
      biomedical literature. This data-driven method paves a new avenue of enquiry into
      the inherent nature of network models for functional brain connectomes.

PMID- 25966471
TI  - Fiber Orientation and Compartment Parameter Estimation From Multi-Shell Diffusion
      Imaging.
AB  - Diffusion MRI offers the unique opportunity of assessing the structural
      connections of human brains in vivo. With the advance of diffusion MRI
      technology, multi-shell imaging methods are becoming increasingly practical for
      large scale studies and clinical application. In this work, we propose a novel
      method for the analysis of multi-shell diffusion imaging data by incorporating
      compartment models into a spherical deconvolution framework for fiber orientation
      distribution (FOD) reconstruction. For numerical implementation, we develop an
      adaptively constrained energy minimization approach to efficiently compute the
      solution. On simulated and real data from Human Connectome Project (HCP), we show
      that our method not only reconstructs sharp and clean FODs for the modeling of
      fiber crossings, but also generates reliable estimation of compartment parameters
      with great potential for clinical research of neurological diseases. In
      comparisons with publicly available DSI-Studio and BEDPOSTX of FSL, we
      demonstrate that our method reconstructs sharper FODs with more precise
      estimation of fiber directions. By applying probabilistic tractography to the
      FODs computed by our method, we show that more complete reconstruction of the
      corpus callosum bundle can be achieved. On a clinical, two-shell diffusion
      imaging data, we also demonstrate the feasibility of our method in analyzing
      white matter lesions. 

PMID- 25966473
TI  - Image Super-Resolution Based on  Structure-Modulated Sparse Representation.
AB  - Sparse representation has recently attracted enormous interests in the field of
      image restoration. The conventional sparsity-based methods enforce sparse coding
      on small image patches with certain constraints. However, they neglected the
      characteristics of image structures both within the same scale and across the
      different scales for the image sparse representation. This drawback limits the
      modeling capability of sparsity-based super-resolution methods, especially for
      the recovery of the observed low-resolution images. In this paper, we propose a
      joint super-resolution framework of structure-modulated sparse representations to
      improve the performance of sparsity-based image super-resolution. The proposed
      algorithm formulates the constrained optimization problem for high-resolution
      image recovery. The multistep magnification scheme with the ridge regression is
      first used to exploit the multiscale redundancy for the initial estimation of the
      high-resolution image. Then, the gradient histogram preservation is incorporated
      as a regularization term in sparse modeling of the image super-resolution
      problem. Finally, the numerical solution is provided to solve the super
      resolution problem of model parameter estimation and sparse representation.
      Extensive experiments on image super-resolution are carried out to validate the
      generality, effectiveness, and robustness of the proposed algorithm. Experimental
      results demonstrate that our proposed algorithm, which can recover more fine
      structures and details from an input low-resolution image, outperforms the state
      of-the-art methods both subjectively and objectively in most cases.

PMID- 25966474
TI  - Covert photo classification by fusing image features and visual attributes.
AB  - In this paper, we study a novel problem of classifying covert photos, whose
      acquisition processes are intentionally concealed from the subjects being
      photographed. Covert photos are often privacy invasive and, if distributed over
      Internet, can cause serious consequences. Automatic identification of such
      photos, therefore, serves as an important initial step toward further privacy
      protection operations. The problem is, however, very challenging due to the large
      semantic similarity between covert and noncovert photos, the enormous diversity
      in the photographing process and environment of cover photos, and the difficulty
      to collect an effective data set for the study. Attacking these challenges, we
      make three consecutive contributions. First, we collect a large data set
      containing 2500 covert photos, each of them is verified rigorously and carefully.
      Second, we conduct a user study on how humans distinguish covert photos from
      noncovert ones. The user study not only provides an important evaluation
      baseline, but also suggests fusing heterogeneous information for an automatic
      solution. Our third contribution is a covert photo classification algorithm that
      fuses various image features and visual attributes in the multiple kernel
      learning framework. We evaluate the proposed approach on the collected data set
      in comparison with other modern image classifiers. The results show that our
      approach achieves an average classification rate (1-EER) of 0.8940, which
      significantly outperforms other competitors as well as human's performance. 

PMID- 25966475
TI  - Attentive Monitoring of Multiple Video Streams Driven by a Bayesian Foraging
      Strategy.
AB  - In this paper, we shall consider the problem of deploying attention to the
      subsets of the video streams for collating the most relevant data and information
      of interest related to a given task. We formalize this monitoring problem as a
      foraging problem. We propose a probabilistic framework to model observer's
      attentive behavior as the behavior of a forager. The forager, moment to moment,
      focuses its attention on the most informative stream/camera, detects interesting
      objects or activities, or switches to a more profitable stream. The approach
      proposed here is suitable to be exploited for multistream video summarization.
      Meanwhile, it can serve as a preliminary step for more sophisticated video
      surveillance, e.g., activity and behavior analysis. Experimental results achieved
      on the UCR Videoweb Activities Data Set, a publicly available data set, are
      presented to illustrate the utility of the proposed technique. 

PMID- 25966476
TI  - Coupled projections for adaptation of dictionaries.
AB  - Data-driven dictionaries have produced the state-of-the-art results in various
      classification tasks. However, when the target data has a different distribution
      than the source data, the learned sparse representation may not be optimal. In
      this paper, we investigate if it is possible to optimally represent both source
      and target by a common dictionary. In particular, we describe a technique which
      jointly learns projections of data in the two domains, and a latent dictionary
      which can succinctly represent both the domains in the projected low-dimensional
      space. The algorithm is modified to learn a common discriminative dictionary,
      which can further improve the classification performance. The algorithm is also
      effective for adaptation across multiple domains and is extensible to nonlinear
      feature spaces. The proposed approach does not require any explicit
      correspondences between the source and target domains, and yields good results
      even when there are only a few labels available in the target domain. We also
      extend it to unsupervised adaptation in cases where the same feature is extracted
      across all domains. Further, it can also be used for heterogeneous domain
      adaptation, where different features are extracted for different domains. Various
      recognition experiments show that the proposed method performs on par or better
      than competitive state-of-the-art methods. 

PMID- 25966477
TI  - Depth-Preserving Warping for  Stereo Image Retargeting.
AB  - The popularity of stereo images and various display devices poses the need of
      stereo image retargeting techniques. Existing warping-based retargeting methods
      can well preserve the shape of salient objects in a retargeted stereo image pair.
      Nevertheless, these methods often incur depth distortion, since they attempt to
      preserve depth by maintaining the disparity of a set of sparse correspondences,
      rather than directly controlling the warping. In this paper, by considering how
      to directly control the warping functions, we propose a warping-based stereo
      image retargeting approach that can simultaneously preserve the shape of salient
      objects and the depth of 3D scenes. We first characterize the depth distortion in
      terms of warping functions to investigate the impact of a warping function on
      depth distortion. Based on the depth distortion model, we then exploit binocular
      visual characteristics of stereo images to derive region-based depth-preserving
      constraints which directly control the warping functions so as to faithfully
      preserve the depth of 3D scenes. Third, with the region-based depth-preserving
      constraints, we present a novel warping-based stereo image retargeting framework.
      Since the depth-preserving constraints are derived regardless of shape
      preservation, we relax the depth-preserving constraints to fulfill a tradeoff
      between shape preservation and depth preservation. Finally, we propose a quad
      based implementation of the proposed framework. The results demonstrate the
      efficacy of our method in both depth and shape preservation for stereo image
      retargeting.

PMID- 25966478
TI  - Extracting 3D layout from a single image using global image structures.
AB  - Extracting the pixel-level 3D layout from a single image is important for
      different applications, such as object localization, image, and video
      categorization. Traditionally, the 3D layout is derived by solving a pixel-level
      classification problem. However, the image-level 3D structure can be very
      beneficial for extracting pixel-level 3D layout since it implies the way how
      pixels in the image are organized. In this paper, we propose an approach that
      first predicts the global image structure, and then we use the global structure
      for fine-grained pixel-level 3D layout extraction. In particular, image features
      are extracted based on multiple layout templates. We then learn a discriminative
      model for classifying the global layout at the image-level. Using latent
      variables, we implicitly model the sublevel semantics of the image, which enrich
      the expressiveness of our model. After the image-level structure is obtained, it
      is used as the prior knowledge to infer pixel-wise 3D layout. Experiments show
      that the results of our model outperform the state-of-the-art methods by 11.7%
      for 3D structure classification. Moreover, we show that employing the 3D
      structure prior information yields accurate 3D scene layout segmentation. 

PMID- 25966479
TI  - Feature-based Lucas-Kanade and active appearance models.
AB  - Lucas-Kanade and active appearance models are among the most commonly used
      methods for image alignment and facial fitting, respectively. They both utilize
      nonlinear gradient descent, which is usually applied on intensity values. In this
      paper, we propose the employment of highly descriptive, densely sampled image
      features for both problems. We show that the strategy of warping the multichannel
      dense feature image at each iteration is more beneficial than extracting features
      after warping the intensity image at each iteration. Motivated by this
      observation, we demonstrate robust and accurate alignment and fitting performance
      using a variety of powerful feature descriptors. Especially with the employment
      of histograms of oriented gradient and scale-invariant feature transform
      features, our method significantly outperforms the current state-of-the-art
      results on in-the-wild databases. 

PMID- 25966480
TI  - Imbalanced Protein Data Classification Using Ensemble FTM-SVM.
AB  - Classification of protein sequences into functional and structural families based
      on machine learning methods is a hot research topic in machine learning and
      Bioinformatics. In fact, the underlying protein classification problem is a huge
      multiclass problem. Generally, the multiclass problem can be reduced to a set of
      binary classification problems. The protein in one class are seen as positive
      examples while those outside the class are seen as negative examples. However,
      the class imbalance problem will arise in this case because the number of protein
      in one class is usually much smaller than that of the protein outside the class.
      To handle the challenge, we propose a novel framework to classify the protein. We
      firstly use free scores (FS) to perform feature extraction for protein; then, the
      inverse random under sampling (IRUS) is used to create a large number of distinct
      training sets; next, we use a new ensemble approach to combine these distinct
      training sets with a new fuzzy total margin support vector machine (FTM-SVM) that
      we have constructed. we call the novel ensemble classifier as ensemble fuzzy
      total margin support vector machine (EnFTM-SVM). We then give a full description
      of our method, including the details of its derivation. Finally, experimental
      results on fourteen benchmark protein data sets indicate that the proposed method
      outperforms many state-of-the-art protein classifying methods.

PMID- 25966481
TI  - Flexible Non-Constrained RF Wrist Pulse Detection Sensor Based on Array
      Resonators.
AB  - This paper presents the development of a non-contact, nonintrusive wrist pulse
      sensor based on the near-field variation of an array resonator. A compact
      resonator and its array were designed and fabricated on flexible substrate. The
      reflection coefficient of the resonator can vary as a function of the distance
      between the resonator and the walls of the major arteries, and the corresponding
      variation is utilized to obtain heart rate information at the wrist. To detect
      very weak pulse signals from the main arteries, a sensitivity enhancement
      technique was devised using a radio frequency (RF) array resonator. The sensor
      system was implemented with an RF switch to combine or select appropriate signals
      from the resonator element and was tested using the 2.4 GHz ISM band. The results
      demonstrated the sensor system's excellent performance in both sequential and
      simultaneous detection schemes. The measurement results showed that a heartbeat
      pulse can be detected from both radial and ulnar arteries via the array
      resonators. Considering the high sensitivity and characteristics, the proposed
      detection system can be utilized as a wearable, long-term health monitoring
      device. 

PMID- 25966482
TI  - Sparse LSSVM in Primal Using Cholesky Factorization for Large-Scale Problems.
AB  - For support vector machine (SVM) learning, least squares SVM (LSSVM), derived by
      duality LSSVM (D-LSSVM), is a widely used model, because it has an explicit
      solution. One obvious limitation of the model is that the solution lacks
      sparseness, which limits it from training large-scale problems efficiently. In
      this paper, we derive an equivalent LSSVM model in primal space LSSVM (P-LSSVM)
      by the representer theorem and prove that P-LSSVM can be solved exactly at some
      sparse solutions for problems with low-rank kernel matrices. Two algorithms are
      proposed for finding the sparse (approximate) solution of P-LSSVM by Cholesky
      factorization. One is based on the decomposition of the kernel matrix K as P P(T)
      with the best low-rank matrix P approximately by pivoting Cholesky factorization.
      The other is based on solving P-LSSVM by approximating the Cholesky factorization
      of the Hessian matrix with rank-one update scheme. For linear learning problems,
      theoretical analysis and experimental results support that P-LSSVM can give the
      sparsest solutions in all SVM learners. Experimental results on some large-scale
      nonlinear training problems show that our algorithms, based on P-LSSVM, can
      converge to acceptable test accuracies at very sparse solutions with a sparsity
      level <1%, and even as little as 0.01%. Hence, our algorithms are a better choice
      for large-scale training problems. 

PMID- 25966483
TI  - Extreme Learning Machine for Multilayer Perceptron.
AB  - Extreme learning machine (ELM) is an emerging learning algorithm for the
      generalized single hidden layer feedforward neural networks, of which the hidden
      node parameters are randomly generated and the output weights are analytically
      computed. However, due to its shallow architecture, feature learning using ELM
      may not be effective for natural signals (e.g., images/videos), even with a large
      number of hidden nodes. To address this issue, in this paper, a new ELM-based
      hierarchical learning framework is proposed for multilayer perceptron. The
      proposed architecture is divided into two main components: 1) self-taught feature
      extraction followed by supervised feature classification and 2) they are bridged
      by random initialized hidden weights. The novelties of this paper are as follows:
      1) unsupervised multilayer encoding is conducted for feature extraction, and an
      ELM-based sparse autoencoder is developed via l1 constraint. By doing so, it
      achieves more compact and meaningful feature representations than the original
      ELM; 2) by exploiting the advantages of ELM random feature mapping, the
      hierarchically encoded outputs are randomly projected before final decision
      making, which leads to a better generalization with faster learning speed; and 3)
      unlike the greedy layerwise training of deep learning (DL), the hidden layers of
      the proposed framework are trained in a forward manner. Once the previous layer
      is established, the weights of the current layer are fixed without fine-tuning.
      Therefore, it has much better learning efficiency than the DL. Extensive
      experiments on various widely used classification data sets show that the
      proposed algorithm achieves better and faster convergence than the existing state
      of-the-art hierarchical learning methods. Furthermore, multiple applications in
      computer vision further confirm the generality and capability of the proposed
      learning scheme. 

PMID- 25966484
TI  - Low-Discrepancy Points for Deterministic Assignment of Hidden Weights in Extreme
      Learning Machines.
AB  - The traditional extreme learning machine (ELM) approach is based on a random
      assignment of the hidden weight values, while the linear coefficients of the
      output layer are determined analytically. This brief presents an analysis based
      on geometric properties of the sampling points used to assign the weight values,
      investigating the replacement of random generation of such values with low
      discrepancy sequences (LDSs). Such sequences are a family of sampling methods
      commonly employed for numerical integration, yielding a more efficient covering
      of multidimensional sets with respect to random sequences, without the need for
      any computationally intensive procedure. In particular, we prove that the
      universal approximation property of the ELM is guaranteed when LDSs are employed,
      and how an efficient covering affects the convergence positively. Furthermore,
      since LDSs are generated deterministically, the results do not have a
      probabilistic nature. Simulation results confirm, in practice, the good
      theoretical properties given by the combination of ELM with LDSs. 

PMID- 25966485
TI  - A Projection Neural Network for Constrained Quadratic Minimax Optimization.
AB  - This paper presents a projection neural network described by a dynamic system for
      solving constrained quadratic minimax programming problems. Sufficient conditions
      based on a linear matrix inequality are provided for global convergence of the
      proposed neural network. Compared with some of the existing neural networks for
      quadratic minimax optimization, the proposed neural network in this paper is
      capable of solving more general constrained quadratic minimax optimization
      problems, and the designed neural network does not include any parameter.
      Moreover, the neural network has lower model complexities, the number of state
      variables of which is equal to that of the dimension of the optimization
      problems. The simulation results on numerical examples are discussed to
      demonstrate the effectiveness and characteristics of the proposed neural network.

PMID- 25966486
TI  - Synchronization of Neural Networks With Control Packet Loss and Time-Varying
      Delay via Stochastic Sampled-Data Controller.
AB  - This paper addresses the problem of exponential synchronization of neural
      networks with time-varying delays. A sampled-data controller with stochastically
      varying sampling intervals is considered. The novelty of this paper lies in the
      fact that the control packet loss from the controller to the actuator is
      considered, which may occur in many real-world situations. Sufficient conditions
      for the exponential synchronization in the mean square sense are derived in terms
      of linear matrix inequalities (LMIs) by constructing a proper Lyapunov-Krasovskii
      functional that involves more information about the delay bounds and by employing
      some inequality techniques. Moreover, the obtained LMIs can be easily checked for
      their feasibility through any of the available MATLAB tool boxes. Numerical
      examples are provided to validate the theoretical results. 

PMID- 25966487
TI  - Asymptotic Normality of the Maximum Pseudolikelihood Estimator for Fully Visible
      Boltzmann Machines.
AB  - Boltzmann machines (BMs) are a class of binary neural networks for which there
      have been numerous proposed methods of estimation. Recently, it has been shown
      that in the fully visible case of the BM, the method of maximum pseudolikelihood
      estimation (MPLE) results in parameter estimates, which are consistent in the
      probabilistic sense. In this brief, we investigate the properties of MPLE for the
      fully visible BMs further, and prove that MPLE also yields an asymptotically
      normal parameter estimator. These results can be used to construct confidence
      intervals and to test statistical hypotheses. These constructions provide a
      closed-form alternative to the current methods that require Monte Carlo
      simulation or resampling. We support our theoretical results by showing that the
      estimator behaves as expected in simulation studies. 

PMID- 25966488
TI  - Automating risk of bias assessment for clinical trials.
AB  - Systematic reviews, which summarize the entirety of the evidence pertaining to a
      specific clinical question, have become critical for evidence-based decision
      making in healthcare. But such reviews have become increasingly onerous to
      produce due to the exponentially expanding biomedical literature base. This study
      proposes a step toward mitigating this problem by automating risk of bias
      assessment in systematic reviews, in which reviewers determine whether study
      results may be affected by biases (e.g., poor randomization or blinding).
      Conducting risk of bias assessment is an important but onerous task. We thus
      describe a machine learning approach to automate this assessment, using the
      standard Cochrane Risk of Bias Tool which assesses seven common types of bias.
      Training such a system would typically require a large labeled corpus, which
      would be prohibitively expensive to collect here. Instead, we use distant
      supervision, using data from the Cochrane Database of Systematic Reviews (a large
      repository of systematic reviews), to pseudoannotate a corpus of 2200 clinical
      trial reports in PDF format. We then develop a joint model which, using the full
      text of a clinical trial report as input, predicts the risks of bias while
      simultaneously extracting the text fragments supporting these assessments. This
      study represents a step toward automating or semiautomating extraction of data
      necessary for the synthesis of clinical trials. 

PMID- 25966489
TI  - Detecting Elementary Arm Movements by Tracking Upper Limb Joint Angles With MARG
      Sensors.
AB  - This paper reports an algorithm for the detection of three elementary upper limb
      movements, i.e., reach and retrieve, bend the arm at the elbow and rotation of
      the arm about the long axis. We employ two MARG sensors, attached at the elbow
      and wrist, from which the kinematic properties (joint angles, position) of the
      upper arm and forearm are calculated through data fusion using a quaternion-based
      gradient-descent method and a two-link model of the upper limb. By studying the
      kinematic patterns of the three movements on a small dataset, we derive
      discriminative features that are indicative of each movement; these are then used
      to formulate the proposed detection algorithm. Our novel approach of employing
      the joint angles and position to discriminate the three fundamental movements was
      evaluated in a series of experiments with 22 volunteers who participated in the
      study: 18 healthy subjects and four stroke survivors. In a controlled experiment,
      each volunteer was instructed to perform each movement a number of times. This
      was complimented by a seminaturalistic experiment where the volunteers performed
      the same movements as subtasks of an activity that emulated the preparation of a
      cup of tea. In the stroke survivors group, the overall detection accuracy for all
      three movements was 93.75% and 83.00%, for the controlled and seminaturalistic
      experiment, respectively. The performance was higher in the healthy group where
      96.85% of the tasks in the controlled experiment and 89.69% in the
      seminaturalistic were detected correctly. Finally, the detection ratio remains
      close ( +/-6%) to the average value, for different task durations further
      attesting to the algorithms robustness.

PMID- 25966490
TI  - Learning a Mahalanobis Distance-Based Dynamic Time Warping Measure for
      Multivariate Time Series Classification.
AB  - Multivariate time series (MTS) datasets broadly exist in numerous fields,
      including health care, multimedia, finance, and biometrics. How to classify MTS
      accurately has become a hot research topic since it is an important element in
      many computer vision and pattern recognition applications. In this paper, we
      propose a Mahalanobis distance-based dynamic time warping (DTW) measure for MTS
      classification. The Mahalanobis distance builds an accurate relationship between
      each variable and its corresponding category. It is utilized to calculate the
      local distance between vectors in MTS. Then we use DTW to align those MTS which
      are out of synchronization or with different lengths. After that, how to learn an
      accurate Mahalanobis distance function becomes another key problem. This paper
      establishes a LogDet divergence-based metric learning with triplet constraint
      model which can learn Mahalanobis matrix with high precision and robustness.
      Furthermore, the proposed method is applied on nine MTS datasets selected from
      the University of California, Irvine machine learning repository and Robert T.
      Olszewski's homepage, and the results demonstrate the improved performance of the
      proposed approach.

PMID- 25966491
TI  - Social Science Collaboration with Environmental Health.
AB  - BACKGROUND: Social science research has been central in documenting and analyzing
      community discovery of environmental exposure and consequential processes.
      Collaboration with environmental health science through team projects has
      advanced and improved our understanding of environmental health and justice.
      OBJECTIVE: We sought to identify diverse methods and topics in which social
      scientists have expanded environmental health understandings at multiple levels,
      to examine how transdisciplinary environmental health research fosters better
      science, and to learn how these partnerships have been able to flourish because
      of the support from National Institute of Environmental Health Sciences (NIEHS).
      METHODS: We analyzed various types of social science research to investigate how
      social science contributes to environmental health. We also examined NIEHS
      programs that foster social science. In addition, we developed a case study of a
      community-based participation research project in Akwesasne in order to
      demonstrate how social science has enhanced environmental health science.
      RESULTS: Social science has informed environmental health science through
      ethnographic studies of contaminated communities, analysis of spatial
      distribution of environmental injustice, psychological experience of
      contamination, social construction of risk and risk perception, and social
      impacts of disasters. Social science-environmental health team science has
      altered the way scientists traditionally explore exposure by pressing for
      cumulative exposure approaches and providing research data for policy
      applications. CONCLUSIONS: A transdisciplinary approach for environmental health
      practice has emerged that engages the social sciences to paint a full picture of
      the consequences of contamination so that policy makers, regulators, public
      health officials, and other stakeholders can better ameliorate impacts and
      prevent future exposure. CITATION: Hoover E, Renauld M, Edelstein MR, Brown P.
      2015. Social science collaboration with environmental health. Environ Health
      Perspect 123:1100-1106; http://dx.doi.org/10.1289/ehp.1409283.

PMID- 25966492
TI  - Validity of Vascular Calcification as a Screening Tool and as a Surrogate End
      Point in Clinical Research.

PMID- 25966493
TI  - Adipocyte Mineralocorticoid Receptor Activation Leads to Metabolic Syndrome and
      Induction of Prostaglandin D2 Synthase.
AB  - Metabolic syndrome is a major risk factor for the development of diabetes
      mellitus and cardiovascular diseases. Pharmacological antagonism of the
      mineralocorticoid receptor (MR), a ligand-activated transcription factor, limits
      metabolic syndrome in preclinical models, but mechanistic studies are lacking to
      delineate the role of MR activation in adipose tissue. In this study, we report
      that MR expression is increased in visceral adipose tissue in a preclinical mouse
      model of metabolic syndrome and in obese patients. In vivo conditional
      upregulation of MR in mouse adipocytes led to increased weight and fat mass,
      insulin resistance, and metabolic syndrome features without affecting blood
      pressure. We identified prostaglandin D2 synthase as a novel MR target gene in
      adipocytes and AT56, a specific inhibitor of prostaglandin D2 synthase enzymatic
      activity, blunted adipogenic aldosterone effects. Moreover, translational studies
      showed that expression of MR and prostaglandin D2 synthase is strongly correlated
      in adipose tissues from obese patients. 

PMID- 25966494
TI  - Severe cases of pandemic H1N1 pneumonia and respiratory failure requiring
      intensive care.
AB  - BACKGROUND: The objective of our study is to analyze the clinical data of
      patients with pandemic H1N1 2009 infection admitted to the intensive care unit
      (ICU) and to report key features observed among these patients. METHODS: A total
      of 18 patients were admitted to our ICU between July and November 2009, with a
      primary diagnosis of influenza. Clinical data were analyzed to identify potential
      risk factors and characteristics thought to affect outcomes. RESULTS: Our
      patients were between ages 23 and 62 (mean 41). In all, 10 were obese. Two had no
      other comorbid conditions and 6 had obesity as their only comorbid condition. The
      most common symptoms were fever, shortness of breath, and cough. Laboratory data
      were notable for elevated creatine kinase levels, transaminitis, and lack of
      leukocytosis. The rapid influenza detection test (RIDT) had a 76% false negative
      result. Patients with a negative RIDT had their infection confirmed with real
      time reverse transcriptase polymerase chain reaction (rRT-PCR). A total of 12
      patients required invasive mechanical ventilation, with over half of whom
      responded only to nonconventional modes of ventilation. Most patients received
      high-dose (150 mg twice daily) oseltamivir. In all, 3 patients died and 11 were
      discharged without any long-term sequalae. CONCLUSIONS: Unlike seasonal
      influenza, our patients were not in the extremes of age. Most were obese and
      presented with severe respiratory distress and hypoxia in the summer months. A
      negative RIDT did not exclude pandemic H1N1 2009. Using a higher dose of
      oseltamivir and nonconventional modes of ventilation may have improved the
      outcome in our subset of patients. Hence, patients with a high clinical suspicion
      of severe influenza infection should be treated early and aggressively, even
      before confirmatory results are available.

PMID- 25966495
TI  - Hemophagocytic syndromes in adult intensive care units: response to Okabe et Al.

PMID- 25966496
TI  - Barriers to Physical Activity in a Mass Transit Population: A Qualitative Study.
AB  - BACKGROUND: The physical inactivity epidemic continues be one of the greatest
      public health challenges in contemporary society in the United States. The
      transportation industry is at greater risk of physical inactivity, compared with
      individuals in other sectors of the workforce. The aim of this study was to use
      the Nominal Group Technique, a focus group technique, to examine mass transit
      employees' perceptions of the barriers to physical activity at their worksite.
      METHODS: Three focus groups (n = 31) were conducted to examine mass transit
      employees' perceptions of barriers to physical activity at the worksite. RESULTS:
      Salient barriers included (1) changing work schedules, (2) poor weather
      conditions, and (3) lack of scheduled and timely breaks. CONCLUSIONS: Findings
      were consistent with previous research demonstrating shift work, poor weather,
      and lack of breaks can negatively impact mass transit employees' ability to be
      physically active. Although physical activity barriers for this population have
      been consistent for the last 20 years, public health practice and policy have not
      changed to address these barriers. Future studies should include conducing focus
      groups stratified by job classification (eg, operators, maintenance, and
      clerical) along with implementing and evaluating worksite-based physical activity
      interventions and policy changes.

PMID- 25966497
TI  - Objective Analysis of Preschoolers' Physical Activity Patterns During Free
      Playtime.
AB  - BACKGROUND: The purpose of this study was to examine the temporal patterns of
      preschoolers' physical activity (PA) levels during a typical outdoor free
      playtime. METHODS: Baseline playtime accelerometer counts (4.3 +/- 0.8 days) from
      3 preschool PA intervention studies were used (n = 326 children, age = 4.0 +/-
      0.8 years). Data were collected using 15-second epochs and classified into
      sedentary, light, or moderate-to-vigorous physical activity (MVPA). Patterns of
      change during playtime were analyzed using orthogonal polynomial comparisons.
      RESULTS: For all ages, there was a U-shaped pattern of change for the percent of
      epochs classified as sedentary [F(1, 323) = 47.12, P < .001) and an inverted U
      shaped pattern of change for the percent of epochs classified as MVPA [F(1,323) =
      32.15, P < .001]. Age-stratified analyses indicated that the 3-year-olds
      maintained the decrease in sedentary time [F(2,323) = 6.408, P = .002] and the
      increase in MVPA [F(2,323) = 3.2, P = .04] to a greater extent than the 4- and 5
      year-olds. CONCLUSIONS: Preschool children gradually became more active during
      the first 10 to 15 minutes of outdoor gross motor playtime and less active over
      the final 10 to 15 minutes of playtime. During the second half of playtime 3-year
      olds maintained these changes to a greater degree than 4- and 5-year-olds.

PMID- 25966499
TI  - [Musculoskeletal tumor].

PMID- 25966498
TI  - Association of Longitudinal Changes of Physical Activity on Smoking Cessation
      Among Young Daily Smokers.
AB  - OBJECTIVE: To our knowledge, no longitudinal epidemiological study among daily
      smokers has examined the effects of physical activity change/ trajectory on
      smoking cessation. The purpose of this study was to examine the longitudinal
      effects of changes in physical activity on smoking cessation among a national
      sample of young (16-24 y) daily smokers. METHODS: Data from the 2003-2005
      National Youth Smoking Cessation Survey were used (N = 1178). Using hierarchical
      agglomerative cluster analysis, 5 distinct self-reported physical activity
      trajectories over 3 time periods (baseline, 12-month, and 24-month follow-up)
      were observed, including stable low physical activity, decreasing physical
      activity, curvilinear physical activity, stable high physical activity, and
      increasing physical activity. Nicotine dependence (Heaviness of Smoking Index)
      and demographic parameters were assessed via survey. RESULTS: With stable low
      physical activity (16.2% quit smoking) serving as the referent group, those in
      the stable high physical activity (24.8% quit smoking) group had 1.8 greater odds
      of not smoking at the 24-month follow-up period (odds ratio = 1.81; 95%
      confidence interval, 1.12-2.91) after adjusting for nicotine dependence, age,
      gender, race-ethnicity, and education. CONCLUSIONS: Maintenance of regular
      physical activity among young daily smokers may help to facilitate smoking
      cessation.

PMID- 25966500
TI  - [An update of classification and new molecular insights-2013 world health
      organization classification of tumors of soft tissue and bone].

PMID- 25966501
TI  - [The role of therapeutic target tyrosine kinases and inhibitors and its current
      situation in bone and soft tissue tumor].

PMID- 25966503
TI  - Findings of research misconduct.

PMID- 25966502
TI  - [Rehabilitation of advanced or recurrent cancer patients].

PMID- 25966504
TI  - What do those drug labels really mean? Claims like 'all day', 'non-drowsy,' and
      'maximum' can be tough to decode. It takes a close read to get what you need.

PMID- 25966505
TI  - How not to get sick(er) in the hospital.

PMID- 25966506
TI  - FAQs about GMOs. It can be tough to figure out why there's so much fuss over
      genetically modified ingredients in food. This will help you sift through the
      facts.

PMID- 25966507
TI  - Experiences of fathers shortly after the birth of their preterm infants.
AB  - OBJECTIVE: To explore the experiences of fathers shortly after the birth of their
      preterm infants. DESIGN/METHOD: A focused ethnography conducted over 33 months
      (2003-2006) in the neonatal intensive care unit (NICU) of a large U.K. National
      Health Trust (NHS) teaching hospital. Data were collected through participant
      observation, in-depth interviews with fathers (n = 10), and an ethnographic
      survey distributed to NICU staff (n = 87). Practices and relationships with
      fathers were concurrently analyzed thematically through the conceptual
      perspective of emotion work. FINDINGS: Fathers' emotional reactions to their
      experiences were described in three themes: emotional withdrawal and control,
      stereotyping, and mixed feelings. Fathers' emotional behaviors were governed by
      complex, culturally determined conventions and expectations. CONCLUSIONS: Fathers
      engaged in considerable effort to manage their emotions as they attempted to
      reconcile the tension between what they wanted to feel and what they thought
      others expected them to feel. The results of this study support the view that
      focusing on emotional externalities alone tends to underplay the amount of
      emotion work carried out by less expressive individuals; this "silent emotion
      work" was characteristic of the fathers in this study.

PMID- 25966508
TI  - Hungry for solutions: businessmen and policymakers are taking a fresh look at how
      to get kids the nutrition their growing bodies and minds need.

PMID- 25966509
TI  - Lethal injection under fire: drug shortages and court challenges are causing
      lawmakers to review their states' method of execution.

PMID- 25966510
TI  - [Using a film to learn about Alzheimer's].

PMID- 25966511
TI  - [The rights of the elderly reaffirmed].

PMID- 25966512
TI  - [Progress on an end of life law].

PMID- 25966513
TI  - [Hearing, communication and old age].

PMID- 25966514
TI  - [What do the elderly and their caregivers wish for?].

PMID- 25966515
TI  - [Paerpa and the negative perception of aging].

PMID- 25966516
TI  - [Swimming for senior balance].

PMID- 25966518
TI  - [Hematology and blood transfusion in the elderly].

PMID- 25966517
TI  - [Caring for a dependent family member, a question of finances?].

PMID- 25966519
TI  - [Anemia in the elderly: diagnosis and therapeutic approach].
AB  - Anaemia is particularly common amongthe elderly population. It is necessary, with
      the aid of the mean glomerular volume, to determine if it is microcytic,
      normocytic or macrocytic. Similarly, the level of reticulocytes indicates whether
      the anaemia is regenerative or non-regenerative. A systematic approach helps to
      identify the causes of this low haemoglobin level. As always in the elderly, it
      is necessary to be aware of their inflammatory status and estimate the iatrogenic
      risk.

PMID- 25966520
TI  - [Malignant blood diseases in the elderly].
AB  - Hematological malignancies are more frequent in elderly patients. Treatment
      efficacy has been improved during the last decade. Long term remission can be
      achieved.The challenge is to identify elderly patients illegible for a curative
      treatment.This highlights the role of geriatric involvement in the management of
      patients with hematological malignancies.

PMID- 25966521
TI  - [Transfusions in geriatrics].
AB  - Elderly people are Darticularlv Drone to anaemia and the need for transfusions.
      However, in response to the known adverse effects of red blood cell transfusions,
      particularly in the context of chronic anaemia, new recommendations have been
      issued. it is always necessary to consider this procedure on a case-by-case
      basis, analysing the risk-benefit ratio.

PMID- 25966522
TI  - [Bibliography. Hematology and blood transfusion].

PMID- 25966523
TI  - [Transfusion, blood products and the principles of their use].
AB  - Almost 3 million blood products are transfused each year in France. More than
      half of packed red blood cell transfusions are given to people over the age of
      69. The regulations concerning the transfusion procedure is identical for all
      patients in order to avoid incompatibilities. However, the frail cardiovascular
      system of the elderly can result in poorly tolerated anaemia. The indication of a
      transfusion in elderly people and their monitoring must therefore be specific to
      this population.

PMID- 25966524
TI  - [Working as a nurse in a nursing home: expertise in gerontology].
AB  - Working with denendent elderly people requires multi-disciplinary abilities:
      theoretical knowledge, inter-personal and relationship skills, a detailed
      knowledge and control of the working practices within the facility and also the
      judgement to seek external care assistance when necessary. The professional nurse
      builds up a soundly based expertise in gerontology from experience gained from
      the wide range of practical situations encountered and by maintaining an ethical
      approach.

PMID- 25966525
TI  - [The speech therapist in geriatrics: caregiver, technician-researcher, or both?].
AB  - Geriatric care mostly consists not in curingthe patient, but supportingthem to
      the end of their life, giving meaning to care procedures and actions through
      speech, touch or look and maintaining a connection.The helping relationship is
      omnipresent and the role of the speech therapist is therefore essential in
      helping to maintain or re-establish elderly patients' abilityto communicate.
      However, todaythis role is struggling to define itself between that of the
      technician-researcher and that of caregiver.

PMID- 25966526
TI  - [The psychological dimensions of falls].
AB  - Falls in the elderly can have serious consequences both functional and
      psychological. In addition to the severe post-fall syndrome, other psychological
      consequences require adapted care. This article intends to highlight the multiple
      dimensions of the psychological impact of falls, through testimony. Loss of
      control of her body, awakening of fear of death, narcissistic injury...; the
      elderly talk about their felt.

PMID- 25966527
TI  - [Preventing pressure ulcers].

PMID- 25966528
TI  - [Respiratory insufficiency in the elderly].

PMID- 25966529
TI  - [Doctors and soldiers during the campaigns of the Revolution and the Empire. The
      bicentenary of the Battle of France (1814-2014). Introduction].

PMID- 25966530
TI  - [The wine from Champagne during the Empire].
AB  - After the revolutionary upheavals (dispersal of the big properties of privileged
      persons and abolition of many rights) and a fold on the local market, the vine
      growing in Champagne found a new balance due to good grape harvests between 1804
      and 1814 and due to the territorial expansion. Without supplanting the red wines,
      the sparkling white wines conquered a new foreign clientele. After the fall of
      the Eagle the traders rushed to the new markets offered by peace.

PMID- 25966531
TI  - [The colors of the health service of the armies of the Empire].

PMID- 25966532
TI  - [Drugs and pharmacists for the army, 1800-1815].
AB  - SUMMARY During this period, the authority was exerted by Parmentier, as the head
      and chief pharmacist for the French armies. For the military hospitals scattered
      all over Europe, he organised the pharmacies services rules, with technical and
      financial concerns. The first aid devices on the battlefield included a special
      box for pharmacy containing ressucitation and siccative items for the wounds, and
      immediately available for the surgeon's use. The qualified pharmacy staff
      exhibited large variations, from 200 to 1.100 people in 1812.

PMID- 25966533
TI  - [The invalids of the Consulate and the Empire].
AB  - The invalid soldiers and officers during French Consulate and 1st Empire were
      taken care of in the National Residence of the Invalids, if they were badly
      wounded and had remained cripple. The conditions to enter the Residence and the
      way of life they lived there are scrutinized.

PMID- 25966534
TI  - [Amputation and equipment of the lower limb during the Revolution and the
      Empire].
AB  - During the French Revolution and Napoleon's campaigns, above-knee or below-knee
      amputations were performed either immediately or with a delay, which favoured
      septic problems. A rapidly operated amputation by a well-trained surgeon was the
      best way to save the life of a soldier who suffered from an open comminuted
      fracture of a limb. The conditions on military campaigns were indeed hard ones:
      doctors and surgeons had practically no resources and the transportation of
      severely injured persons was difficult. Such conditions favoured the pain and the
      danger caused by an injury, and it was rather impossible for the medical corps to
      lavish repeated treatments on the wounds. The amputated soldiers were then given
      prostheses: either a traditional peg-leg, with a flexed knee joint for trans
      tibial amputations, or an "imitative" prosthesis, which tended to look like a
      real leg with eventually an articulated knee or foot. The author mentions famous
      or unrecognized amputated men, describing significant events.

PMID- 25966535
TI  - [Can we speak of the management of pain under the Empire?].
AB  - It is essential first to disregard all our knowledge and current certainties to
      plunge two centuries behind. Pain is recognized: physical, moral, chronic, acute.
      The story of analgesia finds the use of poppy, but with equal components, in
      variable quantity, the analgesic potion could be transformed into a poison. In
      the 17th century Sydenham vulgarizes the use of the laudanum known since the
      16th, and the first general anesthesia will take place in 1846, we can say that,
      under the Empire, we are in the prehistory of the anesthesia. The positioning of
      the doctors and the surgeons in front of the pain is ambiguous. The pain is lived
      as inevitable, the first quality of the surgeon is its operating speed which
      allows to limit the duration of the sufferings. The practitioners in the contact
      of the suffering are going to try hard to develop clevernesses and subtleties to
      decrease this daily pain. The physical ways as baths or showers, bloodletting in
      the inflammatory pains, plants with antispasmodic property (valerian, peony,
      hemlock) and other more or less trivial pharmacological ways. On the battlefield,
      the ways are even more rationalized and limited, first the pharmacological ways
      with the laudanum and the liqueur of Hoffmann, surgery which, by a violent but
      brief pain, solves the problem of the traumatic pains. Dominique Larrey notices
      the analgesic effects of the cold, but he does not seem to have voluntarily used
      it. Acute drunkenness is recognized as dangerous. We are struck by the number of
      description of violent suicides, in particular at the Hotel National des
      Invalides. Just like physical pain, moral suffering is recognized as a disease,
      described as melancholy but without any practical or therapeutic consequence.
      Under the Empire, pain is taken care of, according to the criteria of the time,
      an inescapable fate of which it is necessary to adapt. The field doctors try hard
      to decrease the pain intensity, but the university medical elites exclude the
      idea to overcome it totally. Nevertheless, thirty years later, general anesthesia
      will become possible.

PMID- 25966536
TI  - [The eagle and the louse: typhus in the Grand Army].
AB  - How is it that lice, such a common parasite, have shaken the Napoleonic empire?
      This paper, based on medical literature and on proven facts, is going to tell the
      history of such a "war pestilence", a "contagious typhus".

PMID- 25966537
TI  - [Dr. Henri Marie Husson (1772-1853) and the introduction of the vaccine in
      Reims].
AB  - Born in Reims, Dr H. M. Husson was appointed as the secretary for the Parisian
      Medical Committee for the Inoculation of the Vaccinia in March 1800. In September
      of the same year, he founded the first provincial Committee for Vaccination in
      Reims. At this occasion, he showed his colleagues the doctors Caque (Hotel-Dieu
      hospital), Navier (General Hospital), Demanche, his father Jean Husson and Dr
      Duquenelle (surgeons at the hotel-Dieu hospital), the techniques to vaccinate, to
      take off the "vaccination fluid", to preserve it and to inject it. He also tought
      them the various methods elaborated by the Committee to differentiate the real
      from the fake vaccinia, based on the looks and evolution of the lesions. As a
      tribute to his colleagues from Reims, to their original works and their efforts
      to spread the use of the vaccination, Husson dedicated to them his Historical and
      Medical Research on Vaccination, "as a display of his unalterable attachment and
      of his most distinguished consideration". Eleven years later, Husson vaccinated
      the King of Rome and, in 1839, he became the president of the French Medical
      Academy.

PMID- 25966538
TI  - [Claude Balme, a caregiver of the Egyptian expedition of Bonaparte (1766-1850)].
AB  - The author explains military surgeon Balme's biograpyhy, especially during
      Bonaparte's Egyptian campaign (1798-1801). As there is some possible confusion
      with another Claude Balme, some archives deserve to be closely scrutinized.
      Through Balme's reports the author insists on his courageous part in several
      scurvy or plague epidemics. He was himself marked on his face; he ended his life
      in Lyons as a town-councillor.

PMID- 25966539
TI  - [Jean-Pierre Boudet, Reims pharmacist (1748-1828)].
AB  - Jean-Pierre Boudet (1748-1828) is a too much unknown apothicary from Rheims, what
      is surprising considering the atypical character and the interest of his long
      carrier: a pharmacist and teacher in Rheims then in Paris, he became an inspector
      of powders and salpetre in the east of France. In 1798 he left the civil pharmacy
      and became a military pharmacist by embarking with Napoleon for the campaign of
      Egypt, which he led until its term, before pursuing his military carrier in
      Prussia and Austria. As a member of the Commission of Sciences and Arts and a
      member of the Institute of Egypt, he widely participated, but with too great a
      modesty, in the scientific works stemming from the campaign of Egypt which had
      aimed to be as military as scientific and artistic.

PMID- 25966540
TI  - [Medical education under the Revolution and the Empire].
AB  - After the suppression of medical education during the French revolution in 1793,
      the lack of caregivers is dramatic, especially in the army. The medical education
      is therefore rehabilitated in 1794 in 3 (then 6) Health Schools, which will
      become Schools of Medicine and Faculties of Medicine, incorporated in 1808 into
      then Imperial University. During 3 years, the courses are theoretical and also
      based on a practical teaching on the patient. The defense of a thesis provides
      access to the title of doctor in medicine or surgery and allows practicing for
      all the pathologies on the entire territory of the Empire. Meanwhile, medical
      courses are given in military hospitals to train officers of health. They are
      dedicated for the service of the army and for minor diseases in rural areas. They
      are authorized to practice only in the department in which they were received.
      The inspectors general provide medical education directly in the military medical
      structures and conduct examinations about medical care. This type of career is
      illustrated by the biography of Surgeon Major Francois Augustin Legay.

PMID- 25966541
TI  - [In the footsteps of Dr. Francois Ribes, surgeon of the 1st division of the so
      called ambulance of the battlefield].
AB  - Francois Ribes was a surgeon at Emperor Napoleon's so called ambulance of the
      battle field but he is not well known despite his high offices. On his record of
      service there are 20 battles, 17 fights and 3 sieges during the Revolution and
      Empire. Beside his numerous campaigns he was a surgeon at the parisian Invalides
      Hospital and was highly thought of as a good anatomist. He wrote 84 articles and
      47 memoirs of which the best known is entitled History of the autopsy and
      embalming of Louis XVIII's corpse. However, as a health officer, he only wrote 40
      pages about his military campaigns, published in 1845.

PMID- 25966542
TI  - [Role of the ordinary surgeon Yvan beside Napoleon I on the night of April 12 to
      13, 1814].
AB  - Alexandre-Urbain Yvan was born on April 28th, 1765 in Toulon, where he entered
      the military hospital as a student at 14. He got acquainted with Napoleon
      Bonaparte during the campaigns of Italy. On May 6th, 1800 the Secretary of the
      war appointed him to the care of the First Consul. He became a close friend of
      the Bonaparte family and obtained the post of ordinary surgeon of the Emperor. He
      was going to follow his illustrious patient as his shadow until April 1814.
      Several arguments evoke Napoleon Ist's suicide attempt, during the night from 12
      to 13 April, in Fontainebleau, after the abdication. He absorbed a poison with
      opium but his menservants thwarted his plan, especially Caulaincourt. Baron Yvan
      was called at the bedside of the dying sovereign and managed to save him by
      making him vomit. For fear of being accused of murder, or for some other reason,
      the surgeon ran away without telling the Emperor. This episode ended definitively
      the relation between Napoleon and Yvan.

PMID- 25966543
TI  - [New progress of diagnosis and treatment of Meniere's disease].

PMID- 25966544
TI  - [The clinical application and significance of vestibular function tests in the
      diagnosis of vertigo disease].

PMID- 25966545
TI  - [Clinical research of the otolith abnormal migration during canalith
      repositioning procedures for posterior semicircular canal benign paroxysmal
      positional vertigo].
AB  - OBJECTIVE: To investigate the risk factor,type and characteristic nystagmus of
      the otolith abnormal migration during diagnosis and treatment for posterior
      semicircular canal benign paroxysmal positional vertigo (PSC-BPPV). The therapy
      and prevention is also discussed. METHOD: Four hundred and seventy-nine patients
      with PSC-BPPV were treated by Epley's canalith repositioning procedures(CRP) from
      March 2009 to March 2012. We observed otolith abnormal migration complicating
      during diagnosis and treatment. According the type of otolith abnormal migration,
      the additional repositioning maneuver was performed. RESULT: The rate of
      complication was 8. 1%(39/479), with canal conversion in 5.4%(26/479) and
      primarily canal reentry in 2.7%(13/479). The rate of incidence of conversion to
      horizontal canal conversion and anterior canal were 4. 8%(23/479)and 0. 6%(3/479)
      respectively. All the patient was cured in follow up. The risk factors were
      unappropriated head movement during or after CRP, including another Dix-Hallpike
      were performed immediately. CONCLUSION: To prevent the complications,the
      pathognostic positioning sequence and angle of head rotation are commenced during
      CRP. Appropriate short time postural restrictions post-treatment is necessary.
      Careful observation of nystagrnus variation is crucial to determine the otolith
      abnormal migration.

PMID- 25966547
TI  - [Treatment of anterior canal benign paroxysmal positional vertigo by Yacovino
      repositioning maneuver].
AB  - OBJECTIVE: To evaluate the efficacy of Yacovino repositioning maneuver in
      patients with anterior semicircular canal benign paroxysmal positional vertigo
      (ASC-BPPV). METHOD: Nine patients were diagnosed as ASC-BPPV from January 2013 to
      October 2014. All the patients were performed with Yacovino repositioning
      maneuver and the effective rate were evaluated by Dix-Hallpike tests. RESULT:
      Among the nine ASC-BPPV patients, 2 cases were successfully controlled by the
      first maneuver, 2 cases by the second time, and the nystagmus of 1 case was
      disappeared after 1 months' follow-up. The remaining 3 cases were respectively
      followed up till 7,8, 12 months with consistent positional downbeat nystagmus.
      CONCLUSION: Being a relative low incidence disease, of ASC-BPPV also has low
      effective rate after Yacovino repositioning maneuver.

PMID- 25966546
TI  - [Analysis of clinical features with benign paroxysmal positional vertigo in
      elderly patients and precautions for canalith repositioning procedure treatment].
AB  - OBJECTIVE: To analyze clinical features with benign paroxysmal positional vertigo
      (BPPV) and discuss the attentions in the canalith repositioning procedures.
      METHOD: A total of 76 male and female patients aged 80 and over with BPPV
      (elderly group) and 76 patients aged 60-65 years old with BPPV (older group) was
      retrospectively analyzed. RESULT: (1)Semicircular canal condition: in elderly
      group, posterior semicircular canal was involved in 72 cases, whereas the
      horizontal semicircular 4 cases. In older group, posterior semicircular canal was
      involved in 70 cases, whereas the horizontal semicircular and multiple canals in
      5 cases and 1 case respectively. (2) Precipitating factors: precipitating factors
      of elderly were variety. Its closely related with emotion, infection, seasonal
      alternation surgery, and trauma. There were significant differences between the
      two groups (P<0. 05). (3) The symptoms of undergoing treatment and post
      treatment: the duration of dizziness and carebaria were significant difference
      after canalith repositioning procedure treatment between two groups (P<0. 05),
      the duration of balance disturbance and symptoms of vegetative nerve functional
      disturbance like nausea and sweating were significant difference (P<0. 05). (4)
      Treatment and outcomes: the remission, partial remission rate were 34. 2 %, 81.
      6% re- spectively, after the first or second time of repositioning treatment. The
      efficacy of repositioning treating at the first time was significantly different
      between two groups (P<0. 05). It was poor efficacy in elderly group. There is no
      difference in efficacy for repositioning treatment at the second or third time
      (P>0. 05). (5) The elderly always accompanied with other medical condition and
      had risk factors of cerebrovascular disease. The efficacy was not associated with
      the complication(P>0.05). However, it was most likely to overtreatment caused by
      emphasizing other medical conditions treatment. BPPV was easy to ignore and
      misdiagnose, meanwhile, delayed the diagnosis and increased the medical costs.
      (6) Many elderly were accompanied cervical spondylosis, lumbar spondylosis body
      stiffness and fear of vertigo which increased the difficulty of repositioning
      treatment. (7) Recurrence: we followed up 2 years after treatment. In older
      group, 11 patients (14. 5%)were relapsed. In elderly group, 29 patients (38. 2%)
      relapsed. There were significant differences between the two groups (P<0. 05).
      CONCLUSION: There are various precipitating factors in elderly patients with
      BPPV, the most frequent precipitating factors were related to psychological
      factor and overfatigue. The symptoms of the patients attack BPPV was always mask
      with other diseases, but do not impact on the efficacy of Canalith repositioning
      at the first time; Even the efficacy of repositioning is poor at the first time,
      it's effective and safety after multiple treatments of repositioning; It
      prolonged the symptoms including carenaria, dizziness and nausea after treatment.

PMID- 25966548
TI  - [The hearing and vestibular evoked myogenic potentials test in patients with
      primary benign paroxysmal positional vertigo].
AB  - OBJECTIVE: To investigate the result of vestibular evoked myogenic potentials
      (VEMP) of primary benign paroxysmal positional vertigo(BPPV)and to identify the
      characteristics in VEMP examination of the primary BPPV and to observe the
      relevance of patients with primary BPPV and abnormal VEMP with hearing loss.
      METHOD: Patients with primary BPPV were tested with pure tone audiometry,
      videonystagmograph and VEMPs test. We analyzed the difference in the two groups
      with normal hearing and hearing loss, discussed the etiology and pathogenesis.
      RESULT: Primary BPPV comprised 23.0% with hearing lost, 77.0% hearing normal. The
      results of oVEMP were abnormal in 79. 7% (59/74) of the cases; and the results of
      cVEMP were abnormal in 66. 2% (49/74) of the cases; oVEMP and cVEMP differences
      to the diagnosis of primary BPPV (P<0. 05); oVEMP and cVEMP differences to the
      diagnosis primary BPPV with hearing lost (P<0. 05). CONCLUSION: oVEMP detection
      positive rate of primary BPPV is higher than cVEMP,which may be due to otolithic
      particles falling from the utricle; positive rate of cVEMP in primary BPPV with
      hearing loss is higher than that of oVEMP, which may related to the cochlear and
      sacculus occured in the same embryonic tissue structure.

PMID- 25966549
TI  - [Diagnosis and therapy for horizontal semicircular canal cupulolithiasis].
AB  - OBJECTIVE: By analysing the video-nystagmography findings of positional tests,to
      evaluate the therapeutic effect of the patients with horikontal semicircular
      canal cupulolithiasis (HSC-Cup). METHOD: A retrospective study of 36 patients
      with HSC-Cup. The induced nystagmus in roll tests was recorded by
      videonystagmography, whose direction, latency, intensity and time characteristics
      were analysed. All of the 36 patients were treated with lying position avoiding
      normal side and oral-taken betahistine mesilate tablets. A week later return
      visits and curative effects evaluation were made. RESULT: Horizontal apogeotropic
      nystagmus was induced by turning left or right in HSC-Cup roll tests. The time of
      latency and duration turning to normal and lesion side were(0. 93 +/- 0. 65)s
      and(1. 01 +/- 0. 78)s, (100.58 +/- 36. 56)s and (118. 65 +/- 143. 71)s, which
      showed no statistically significant difference (P>0. 05). The duration of
      nystagmus was more than 60 seconds. The intensity of nystagmus turning to normal
      and lesion side were(45.58 +/- 28.71) degrees /s and (20.42 +/- 16. 64) degrees
      /s. The intensity turning to normal side was greater than lesion side obviously.
      The difference was statistically significant (P<0. 05). Twenty-three patients
      withright HSC-Cup, and 13 patients with left HSC-Cup were taken in count. They
      were treated with above methods and return visit a week later. Twenty-eight
      patients (77. 77%) were cured, 36 patients (100. 00%) were improved. There were 4
      patients recurrence during the follow-up. CONCLUSION: The direction and duration
      time of induced nystagmus are available to diagnose the HSC-Cup. The lesion side
      may determined according to the intensity of induced nystagmus. Lying position
      avoiding normal side and oral-taken betahistine mesilate tablets is an effective
      treatment methods for HSC-Cup.

PMID- 25966550
TI  - [The analysis of nystagmus in patients with posterior canal benign paroxysmal
      positional vertigoin positioning test].
AB  - OBJECTIVE: To analyze and summarize nystagmus of patients with posterior canal
      benign paroxysmal positional vertigo (BPPV) in positioning test,and to improve
      the diagnosis and treatment of posterior canal BPPV (PSC-BPPV). METHOD: The
      present study was conducted on 175 patients who had unilateral BPPV of the
      posterior semicircular canal (PSC). Their positional nystagmus recorded by
      videnonystagmography in Dix-Hallpike test,roll test and roll over test were
      analyzed to summarize the characteristics of nystagmus on nystagmograph of PSC-BP
      PV. RESULT: Of the 175 patients, lesion was located in the left PSC in 69 (39.4%)
      patients,the right PSC in 106 (60. 6%)patients. The nystagmus of patients with
      PSC-canalithiasis showed upward on the vertical phase of nystagmograph and
      orientated the different side on horizontal phase in the head hangging position.
      The horizontal phase pointed to the contralateral side in 47(26. 9%) patients,
      the ipsilateral contralateral side in 100(57. 1%) patients,no significant reverse
      ingredients in 28(16.0%) patients. When these patients returned to sit,139(79.4%)
      patients showed down beating positioning nystagmus, whereas 36 (20. 6%) patients
      with no nystagmus only had a short vertigo or dizziness. The horizontal phase of
      the 139 patients pointed to the contralateral side in 40(22. 9%) patients,the
      ipsilateral contralateral side in 68(38. 9%) patients,no significant reverse
      ingredients in 31(17. 7%) patients. In roll test,12 patients of the right PSC
      BPPV presented an up-beating rotatory nystagmus when the head turned to right,and
      5 patients of the left PSC-BPPV presented a down-beating rotatory nystagmus when
      the head turned to left. When the patients changed body from the left lateral
      position to the right lateral position in the roll over test, 74(42. 3%)
      patientsshowed vertical positioning nystagmus. In 30 patients who presented an up
      beating nystagmus, there were 25(83. 3%) patientscame from the right PSC-BPPV. In
      44 patients who presented a down-beating nystagmus, there were 36(81. 8%)
      patientscame from the left PSC-BPPV. The direction of the vertical nystagmus was
      highly correlated with the judgment about the side of the PSC-BPPV in roll over
      test (P<0. 01). CONCLUSION: The patient with PSC-canalithiasis showed an
      uncertain direction in torsional nystagmus in Dix-Hallpike test,the diagnosis was
      mainly concern with the vertical nystagmus. When we found a rotatory nystagmus
      with much more up-beating nystagmus in roll test, it might be PSC-BPPV. We also
      can use the roll over test to diagnose the location of the otolith in which side
      of the PSC-BPPV.

PMID- 25966551
TI  - [Application of the tragus cartilage in the tympanoplasty].
AB  - OBJECTIVE: To observe the application of the tragus cartilage in tympanoplasty.
      METHOD: Thirty-eight patients with tympanoplasty carried out tragus cartilage
      perichondrium repairing tympanic membrane. The air-bone gap changes and the
      recovery of patients'tympanic membrane were evaluated at pre-operative and two
      months after the operation. RESULT: Thirty-one patients finishing follow-up visit
      showed tympanic membrane healed and looked like normal appearance in 1 to 3
      months after the operation. The postoperation narrow of the air-bone gap >18 dB,
      tragus looked normal. CONCLUSION: Tympanic membrane reconstruction using the
      tragus cartilage-perichondrium is feasible for tympanoplasty, and the survival
      rate and postoperative hearing would be acceptable.

PMID- 25966553
TI  - [Relationships of electrophysiological characteristic between speech evoked
      auditory brainstem response and auditory mismatch negativity].
AB  - OBJECTIVE: To investigate the relationships of electrophysiological
      characteristics between speech evoked auditory brainstem response (s-ABR) and
      auditory mismatch negativity (MMN), so as to provide more clues for the mechanism
      of speech cognitive behavior. METHOD: Thirty-three ears in 33 normal hearing
      adults were included in this study. Their s-ABR were recorded with speech
      syllables /da/ at 80 dB HL intensity. Meanwhile, two MMNs were recorded with 1
      kHz frequency deviant extent and 40 dB intensity deviant extent in them. The
      electrophysiological characteristics of s-ABRs and MMNs, as well as the
      relationships of MMN latencies between s-ABR parameters including latencies in
      time domain, fundamental frequency(F0) and first formants(F1) in frequency domain
      were analyzed statistically. RESULT: MMN latency of frequency deviance showed a
      negative correlation tendency with s-ABR transient components, and it showed a
      positive trend with sustained components of s-ABR. While MMN latency of intensity
      deviance showed a positive correlation with s-ABR latency of peak V, A and D
      respectively, and it negatively showed a correlation with s-ABR latency of other
      peak s and amplitude of F0 and FI respectively. Only the s-ABR latency of peak F
      and MMN latency of frequency deviance, and the F0 amplitude of s-ABR and MMN
      latency of intensity deviance were moderate correlation statistically.
      CONCLUSION: It was probably the neurons of frequency deviant MMN unmatched the
      characteristics of frequency with the neurons of s-ABR transient component, but
      well matched the characteristics of frequency with the neurons of s-ABR sustained
      component. Similarly, the neurons of intensity deviant MMN probably matched the
      characteristics of intensity with neurons of different components of s-ABR or
      not. These results may formed as a valuable clue for further investigation of
      speech perception and temporal processing abilities.

PMID- 25966552
TI  - [Allergic factors affect on severity of chronic rhinosinusitis and postoperative
      outcomes].
AB  - OBJECTIVE: To investigate whether the allergic factors impact the severity of
      chronic rhinosinusitis or not, further more, to explore the relationship between
      allergic rhinitis and chronic rhinosinusitis. METHOD: A retrospective review was
      done on 103 patients. All of these patients were under functional intranasal
      endoscopic sinus surgery after expectant treatment is ineffective. We devided the
      patients into different groups according to the result of skin prick and specific
      IgE and if there is difference in VAS score, Lund and Kennedy endoscopic score,
      Lund-Mackay CT score between the groups. We also analysed the symptoms in
      different chronic rhinosinusitis patients allerged to variant kinds of allergen.
      The SPSS 17.0 software was used to analyze the data. Statistical analysis was
      performed by t-test, rank order test or chi2 test. RESULT: The duration of the
      disease, VAS score of nasal blockage, score of Lund-Mackay CT and Lund and
      Kennedy endoscopic before the operation were in no statistical sense after when
      compared with the two groups of patients with chronic rhiriosinusitis who grouped
      according the result of skin prick and specific IgE. The VAS score of facial
      pressure and loss of smell was higher in patients with chronic rhinosinusitis
      which the skin prick and specific IgE were positive. The VAS score of nasal
      discharge was higher in patients with chronic rhinosinusitis who got negative
      skin prick and specific IgE result. The symptoms of chronic rhinosinusitis
      improved with operation no matter the group of skin prick and specific IgE
      positive or negative and VAS score of nasal blockage improved significantly in
      negative group. The symptoms of sneezing, rhinorrhoea and rhinocnesmus improved
      after operation among the chronic rhinosinusitis patients with skin prick and
      specific IgE. The number of cockroach allergy is larger among the patients with
      chronic rhinosinusitis without polyps than the one among the patients with
      chronic rhinosinusitis with polyps. CONCLUSION: Allergic factor didn't impact
      much the severity of chronic rhinosinusitis patients who were failed in expectant
      treatment, besidesthe postoperative outcomes showed that only influence the
      severity of nasal discharge, facial pressure and loss of smell. Different kinds
      of allergen were found between the patients of chronic rhinosinusitis with or
      without polyps. No significantly functional endoscopic sinusitis sugrery outcome
      were related to the allergic factor. But the allergic factor may interfere the
      remission of nasal discharge after surgery.

PMID- 25966554
TI  - [Study on 2,747 cases of inner ear malformation for its classification in patient
      with sensorineural hearing loss].
AB  - OBJECTIVE: Analyze the data of the patients with sensorineural hearing loss in
      China and study the classification and incidence of inner ear malformationsby the
      high-resolution computed tomography. METHOD: The investigation took a
      retrospective review of CT findings relating to the 2,747 cases of outpatients.
      The inner ear malformations diagnosed by CT were classified according to the
      methods proposed by Sennaroglu. RESULT: (1)843 cases of inner ear malformations
      were found in 2747 cases of patients with sensorineural hearing loss by CT
      examination. The incidence of inner ear malformation was 30.69%(843/2747). (2)
      The epidemiological information of 843 cases of inner ear malformation according
      to Sennaroglu's classification was as follows: cochlea was 52. 31%(441/843),
      simple vestibular aqueduct was 40.33%(340/843), simple vestibular/ semicircular
      canal/internal auditory canal were 7. 35%(62/843) of the group. (3) 441 cases of
      cochlea malformation were consisted of these types of malformation: Michel
      deformity was 1.13% (5/441), cochlear aplasia was 1. 81% (8/441), common cavity
      deformity was 3. 17% (14/441), incomplete partition type I was 8. 62% (38/441),
      cochlea hypoplasia was 9. 07% (40/441) and incomplete partition type II was 76.
      19% (336/441) of the group. CONCLUSION: The results suggested that 30. 69% cases
      of inner ear malformation can be found in patients with sensorineural hearing
      loss, which is more higher than reported by the high-resolution computed
      tomography. Sennaroglu's classification is instructively significant in
      investigating the status of inner ear malformations.

PMID- 25966555
TI  - [Study on delivery efficiency and cytotoxicity of Hela cells with mPEG-PLGA-BSA
      FITC-NPs nanocarrier].
AB  - OBJECTIVE: To construct and obtain ideal protein delivery vectors by researching
      the delivery efficiency and cytotoxicity to Hela cells using mPEG-PLGA-BSA-FITC
      NPs. METHOD: The mPEG-PLGA nanoparticle was obtained through surface modification
      of PLGA with PEG, and deliver BSA-FITC into Hela cells in vitro. The positive
      cells were counted by Laser scanning confocal microscopy and the survival rate of
      Hela cells was calculated by MTT assay at different time points. RESULT: mPEG
      PLGA-BSA-FITC-NPs shows the classic nanometer size, and the encapsulation
      efficiency reached 51. 2%. At the same time, the nanoparticles possess
      characteristics of slow release. By optimizing the delivery conditions, the
      highest efficiency of mPEG-PLGA-BSA-FITC-NPs was above 65.2%, and the cellular
      viability was about 85.7%. CONCLUSION: mPEG-PLGA-BSA-FITC-NPs nanoparticles can
      successfully carry the target protein into cells as safe and effective as novel
      delivery materials of protein in vitro, and has shown slow release
      characteristics. The mPEG-PLGA-BSA-FITC-NPs provide ideal delivery vector for
      future application in clinical treatment of disease using nano-materials.

PMID- 25966556
TI  - [The correlation analysis of coagulation detection and blood routine parameters
      of sudden hearing loss].
AB  - OBJECTIVE: Through the analysis of coagulation convention and blood routine
      parameters of sudden hearing loss (SHL) patients, further prove the correlation
      of sudden deafness and the the inner ear microcirculation, to guide clinical
      diagnosis and treatment. METHOD: Select 424 patients (448 ears) with sudden
      deafness in our department to SHL group. According to hearing curve is classified
      into low intermediate frequency descent group, high frequency drop and full
      frequency group, and drawing 244 cases in the same period of hospitalization
      deviated septum, vocal cord polyp patients as control group. All patients'
      coagulation detection, D-dimer, blood leukocytes, neutrophils and platelet count
      percentages were analyzed. Then a meaningful factor multivariate Logistic
      regression analysis was made. RESULT: There was a statistically significant
      difference between the two groups' prothrombin time, international normalized
      ratio, activated partial thromboplastin time, thrombin time measurement,
      fibrinogen, D-dimer, platelet count, white blood cell, neutrophil ratio(P<0.05);
      Logistic regression analysis showed that the prothrombin, thrombin time
      measurement, fibrinogen, D-dimer, neutrophil incidence of sudden hearing loss
      associated risk factors. CONCLUSION: SHL in patients with coagulation dysfunction
      may be involved in the occurrence of SHL development mechanism, and there is a
      correlation of the SHL and the dysfunction of inner ear microcirculation.

PMID- 25966557
TI  - [The study of clinical characteristics of sudden sensorineural hearing loss
      patients with tinnitus].
AB  - OBJECTIVE: To analysis the characteristics of sudden sensorineural hearing loss
      (SSHL) patients with tinnitus, and explore the relationship of characteristics of
      tinnitus and audiology. METHOD: Patients diagnosed as SSHL with tinnitus were
      studied in the research. All patients' clinical features were analyzed, such as
      tinnitus frequency, pure tone audiometry, tinnitus, hearing loss degree, results
      of residual inhibition test. RESULT: Thirty cases were identified as mild degree
      hearing loss, 13 cases as moderate degree, 28 cases as severe degree and 34 cases
      as profound degree. And hearing impaired frequency of 13 cases was ascertained at
      low-frequency, 39 cases at middle-high-frequency, and 53 cases at full-range
      frequency. The incidence of patients with low-frequency was about 41. 9%
      (44/105), and it was about 21. 9% (23/105) in those with middle-frequency. And it
      was 36. 2% (38/105) in cases of high-frequency tinnitus. The chi-square test show
      statistically significant differences between patients with the low-frequency,
      middle-frequency and high-frequency of the hearing loss (P<0. 05). In tinnitus
      residual inhibition test, positive rate of convergence type masking curve was
      about 72.0%, tinnitus separated type masking curve 20.0%, overlapping type was
      57.9%, and the spacing type was 43.5%. There was a statistically significant
      difference among cases with different type masking curve (P<0. 05)with the
      spacing residual inhibition test positive rate. CONCLUSION: There are individual
      differences of clinical characteristics among SSHL patients with tinnitus.
      Tinnitus frequency is consistent with the frequency of hearing loss. Patients had
      the more serious the degree of hearing loss, who had more serious tinnitus
      grading. Cases with the converged type curve will be fit for tinnitus masking.
      Therefore, combining the tinnitus detection with the audiological tests, we could
      obtain the clinical characteristics of SSHL patients with tinnitus.

PMID- 25966558
TI  - [Meta-analysis of PET/CT for diagnosis of residual/recurrent nasopharyngeal
      carcinoma].
AB  - OBJECTIVE: To assess the diagnostic value of 18-fluoro-2-deoxyglucose positron
      emission tomography/computed tomography (18F-FDG PET/CT) in detecting
      residual/recurrent nasopharyngeal carcinoma. METHOD: The literatures published
      between January 1990 and September 2013 were searched in PubMed, EM-BASE, EBSCO,
      Web of Science, CBM, CNKI, VIP and Wanfang databases. Two researchers
      independently selected studies, extracted data and assessed the quality of
      included studies according to the QUADAS tool. Summary sensitivity, specificity,
      diagnostic odds ratios (DOR), and receiver-operating characteristic (SROC) curves
      were obtained using Meta-Disc software. Subgroup analysis was also conducted.
      RESULT: Twenty-six studies were included in this meta-analysis, involving 1203
      patients. The pooled sensitivity, specificity and DOR were 0. 92 (95% CI:0.89
      0.94), 0. 87 (95% CI:0.84-0.90) and 51. 10 (95% CI:34.29-76.15), respectively.
      The area under the curve (AUC) and Q index estimate for PET/CT were 0. 9494 and
      0. 8897, respectively. The results of subgroup analysis showed no significant
      differences between subgroups(P>0.05). CONCLUSION: In a word, 18F-FDG PET/CT
      performed well for diagnosis of residual/recurrent nasopharyngeal carcinoma, with
      relatively high sensitivity and specificity.

PMID- 25966559
TI  - [Cetuximab in head and neck squamous cell carcinoma: a systematic review and Meta
      analysis].
AB  - OBJECTIVE: To-evaluate the role and clinical value of cetuximab in the treatment
      of head and neck squamous cell carcinoma (HNSCC), and figure out its
      effectiveness and application, so as to develop evidence-based recommendations
      for treatment. METHOD: We comprehensively searched the CBM, Pubmed, EMBASE, and
      the Cochrane databases to identify published studies on the effect of cetuximab
      in HNSCC patients. Primary outcomes included overall survival (OS), progression
      free survival(PFS) and overall response rate(ORR). Secondary outcomes included
      serious adverse events, such as neutropenia, anemia, thrombocytopenia, skin
      reactions, hypokalemia, vomiting, asthenia, hypomagnesemia, dyspnea and sepsis.
      Results were dispalyed as risk ratio (RR), odds ratio (OR), mean difference (MD)
      and 95% CI. RESULT: A Meta-analysis was conducted on 4 randomized controlled
      trials, including 2 trials comprising 1,319 patients with locally advanced HNSCC
      and 2 trails comprising 559 patients with recurrent or metastatic HNSCC. For
      locally advanced HNSCC, the 2 year PFS and OS showed no significant differences
      in patients received cetuximab or not (PFS fixed effect: RR=1.02, 95%CI 0.92
      1.12, P>0.05; OS fixed effect: RR=1.06, 95%CI 1.00-1.13, P>0.05, respectively).
      Grade 3-4 dysphagia was also similar in patients treated with cetuximab or no
      cetuximab (dysphagia: fixed effect: RR = 0.92; 95% CI 0.84-1.02, P>0. 05). Only
      grade 3-4 mucositis and skin reaction showed statistical significance between
      patients treated with cetuximab and patients with no cetuximab (mucositis: fixed
      effect: RR=1.21; 95%CI 1.07-1. 36, P<0. 05; skin reaction: fixed effect: RR=1.99;
      95%CI 1.39-2.85, P<0.05, respectively). For recurrent or metastatic HNSCC, the OS
      overall mean difference was 2.41 (95% CI 0.96-3.86, P<0.05), the PFS overall mean
      difference was 2. 06 (95% CI 1.34 - 2.77, P<0.05), and the ORR overall Odds ratio
      was 2.38 (95% CI 1.60-3.54,P<0.05), suggesting significant effect of cetuximab in
      improving the prognosis of R/M HNSCC. Owing to small number of trials it was not
      possible to assess the presence of publication bias. Of note, the 1 year survival
      overall Odds ratio was 1.39 (95% CI 0.98-1.97, P>0.05). The grade 3 or 4 adverse
      effects were described in 83. 4% of patients in cetuximab group and 75. 5% of
      patients in no cetuximab group. The overall side effects risk ratio suggested
      statistically significant difference between patients treated with cetuximab and
      pa- tients with no cetuximab (RR=1.11, 95% CI 1.01-1.20, P<0.05, P =47%).
      CONCLUSION: The 2 year progression-free survival and overall survival were
      similar between cetuximab group and no cetuximab group in patients with locally
      advanced head and neck squamous cell cancer. Data are limited and the benefits of
      cetuximab on this outcome remain uncertain. Impact of grade 3-4 dysphagia was
      similar in both groups, however, the incidence of grade 3-4 mucositis and skin
      reaction were lower in patients treated with cetuximab. Existing randomized
      controlled trials provided a scientific evidence for the use of cetuximab in R/M
      HNSCC. The conclusion of the study is based on limited number of RCT, so further
      investigation is still needed before firm recommendations of cetuximab can be
      made in the treatment of HNSCC.

PMID- 25966560
TI  - [The analysis of masking therapy in the early stage of the patients with noise
      induced tinnitus].
AB  - OBJECTIVE: To explore the effect of masking therapy for the early stage of the
      patients with noise-induced tinnitus,and imply the treatment for patients with
      noise-induced tinnitus. METHOD: Sixty-eight cases with tinnitus were studied. All
      the patients took the audiological examinations and tinnitus tests firstly, and
      accepted the masking therapy for 6 months. The therapeutic effiency was evaluated
      according to tinnitus handicap inventory (THI) and subjective visual-analogue
      scale (VAS). The minimum masking intensity was also evaluated. RESULT: The
      majority of the patients with noise-induced tinnitus (59 cases, 86. 8%) had
      tinnitus frequency of 4 kHz,and most of them (44 cases, 64. 7%) had positive
      residual inhibition tests. Tinnitus completely disappeared in 3 cases after
      masking therapy, and the efficiency of this treatment is 83. 8%. There was
      significant difference in the scores of THI and VAS before and after therapy(P<0.
      01), and there was also significant difference in the minimum masking intensity
      (P<0. 01). CONCLUSION: Masking therapy is the most important treatment for the
      patients in the early stage of noise-induced tinnitus. The therapeutic effiency
      is significant and should be promoted.

PMID- 25966561
TI  - [A retrospective study of coblation-assisted treatment in adult with obstructive
      sleep apnea-hypopnea syndrome].
AB  - OBJECTIVE: To investigate the therapeutic effects of 894 coblation-assisted
      treatment in adult with obstructive sleep apnea-hypopnea syndrome. METHOD: A
      review of 894 coblation-assisted treatment in adult with obstructive sleep apnea
      hypopnea syndrome was presented with respect to the sleep monitoring results, SF
      36 health questionnaire survey, therapeutic effects and complications. RESULT:
      After operation for 6 months, the patients' sleep Monitoring results were
      improved remarkably (P<0. 01) and their symptoms of snore or choke got improved.
      SF-36 health questionnaire survey showed that social function, energy and mental
      health dimension scores were significantly higher than the preoperative (P<0.
      05). There were 18 patients suffered Secondarily bleeding within 2 weeks and 23
      patients recrudesced within 1 year. CONCLUSION: Radio frequency coblation is an
      applicable method of therapy for patients with obstructive sleep apnea-hypopnea.
      The treatments differ with the obstructive location and character of upper
      airway.

PMID- 25966562
TI  - [The expression and significance of adaptin-2 in mice cochlea].
AB  - OBJECTIVE: To investigate the expression of adaptin-2(AP-2) in mice cochlea and
      to discuss the probable role in the endocytosis of hair cells. METHOD: Laser
      scanning confocal microscopy and immune-fluroscence histochemistry were performed
      in this study. RESULT: In mature mice cochlea, the immunoreactivity for AP-2 was
      found in the inner hair cells cytoplasm. This protein mainly expressed in the
      hair cells basal part and nearby the ribbon synapse. CONCLUSION: AP-2 protein
      mainly expressed in the hair cells synaptic activity zone , which suggested that
      AP-2 could play an important role in the synaptic vesicle endocytosis. This
      finding built the foundation for the further research involved in the
      physiological and pathological role of AP-2.

PMID- 25966563
TI  - [Clinical study on rescection operation of adult preauricular sinus in stage of
      abscess].

PMID- 25966564
TI  - [Study of retroauricular flap combing with palatine mucose in repair full
      thickness eyelid defects].

PMID- 25966565
TI  - [A case of parapharyngeal space infection followed abdominal pain].
AB  - Descending necrotizing mediastinitis that has an abdominal pain as a main
      clinical manifestation is seldom. Here one case is reported. At the beginning,
      the patient had pharyngalgia and his swallowing was not smooth. After that,
      abdominal pain became a main symptom. Pharyngalgia relieved . However CT showed
      mediastinal infection. Surgical drainage,antibiotics treatment and nutritional
      support were performed. The patient was cured.

PMID- 25966566
TI  - [Myeloidleukemia with external auditory canal granulocytic sarcoma: a case
      report].
AB  - We describe a 44-year old man who suffered an isolated external auditory canal
      granulocytic sarcoma in remission of acute myeloid leukemia. The patient
      confirmed acute promyelocytic leukemia three years ago and the disease was in
      remission after treatment. Two months ago he presented pain and hearing loss in
      the left ear and the symptom developed gradually. At otoscopic examination a
      tumoral lesion was noted in the external auditory canal and computerized
      tomography scan showed a mass in the left external acoustic meatus without bone
      erosion.

PMID- 25966567
TI  - [Auricle fibrosarcoma:a case report].
AB  - A male patient, 67 years old, was admitted with the left auricle neoplasm over
      two months, increased rapidly for 10 days, on November 5, 2013. The tumer is
      about 2. 0 cm ** 2. 0 cm size, smooth surface, no burst, hard, painless, and
      immobilization. After admission biopsy, the pathological report: "spindle cell
      sarcoma", thin a total resection of the left auricle under local anesthesia was
      made, postoperative pathological report: tumor by short of spindle cells,
      arranged in bunchiness, a small number of seats is arrangeA striate;The nuclei
      are hyperchromatic and part of the visible nucleoli and empty bright cytoplasm,
      pathological nuclear fission was visible. "Scar" on the matrix of collagen,
      hardening, and change the glass samples. The tumor destruction of cartilage.
      immunohistochemical stainin : Vimentin (+), CD99 (-), Bcl-2 (-), CD34 (-), SMA (
      ), Des (-), HMB45 (-), MelanA(-), S-100(-), CK(-). Diagnosis as fibrosarcoma. The
      patient refused any radiation or chemotherapy. Postoperative follow-up of 8
      months, no local recurrence and distant metastasis.

PMID- 25966568
TI  - [The research progress of unilateral enlargement of the vestibular aqueduct].
AB  - Unilateral enlargement of the vestibular aqueduct (EVA)is a relatively rare
      disease. Bilateral EVA was found to be more common than unilateral EVA. There are
      significant differences in clinical features and molecular etiology between
      unilateral EVA and bilateral one. This article reviewed related researches of the
      unilateral EVA in clinical characteristics, molecular etiology and pathogenic
      mechanism.

PMID- 25966569
TI  - [EEG-correlates of pilots' functional condition in simulated flight dynamics].
AB  - The spectral characteristics of the EEG recorded on two professional pilots in
      the simulator TU-154 aircraft in flight dynamics, including takeoff, landing and
      horizontal flight (in particular during difficult conditions) were analyzed. EEG
      recording was made with frequency band 0.1-70 Hz continuously from 15 electrodes.
      The EEG recordings were evaluated using analysis of variance and discriminant
      analysis. Statistical significant of the identified differences and the influence
      of the main factors and their interactions were evaluated using Greenhouse -
      Gaiser corrections. It was shown that the spectral characteristics of the EEG are
      highly informative features of the state of the pilots, reflecting the different
      flight phases. High validity ofthe differences including individual
      characteristic, indicates their non-random nature and the possibility of
      constructing a system of pilots' state control during all phases of flight, based
      on EEG features.

PMID- 25966570
TI  - [Binocularly co-activation modulate development of functional modular systems in
      cats visual cortex].
AB  - Using optical imaging technique and method for histochemical cytochrome oxidase
      revealing we investigated in three kitten's groups (two experimental and one
      control) a rhythmically light stimulation on ontogenetic development of
      orientation columns and cytochrome oxidase blobs in visual area 18. Experimental
      animals were stimulated by rhythmical light for 3 hrs or 12 hrs per day
      respectively. It was first obtained that binocular co-activation per se, not
      accompanied by strabismus, indeed influences cortical columns formation during
      critical period. We show an opposite effect of stimulation on two different types
      of cortical columns, and also revealed that these affects are have retained for
      at least 2 weeks after stimulation was terminated. It was obtained that duration
      of rhythmically light stimulation determines a volume of functional and anatomic
      alterations: alterations revealed were more pronounced in animals stimulated
      for12 hrs per day.

PMID- 25966571
TI  - [Stress reactivity and stress-resilience in the pathogenesis of depressive
      disorders: involvement of epigenetic mechanisms].
AB  - The data of epigenetic studies of stress reactivity and resilience in the
      pathogenesis of depression in experimental animals and humans subjected to stress
      at different periods of life are analyzed. Specific chromatin modifications,
      first of all histone acetylation and methylation, are controlling expression of
      definite genes in distinct brain structures. Epigenetic modulation of particular
      genes related to development of pro-depressive or antidepressive stress response
      are discussed (5HT transporter and receptors, corticotropin releasing hormone,
      glucocorticoid and their receptors, BDNF and other neurotrophic factors).

PMID- 25966572
TI  - [The brain executive systems].
AB  - The analysis of neuromorphological, neurophysiological, neurocognitive and
      neuropsychological data demonstrates the specific involvement of lateral, medial,
      orbital and rostral parts of prefrontal cortex in the selective regulation and
      organization of goal-directed behavior. Functional specialization of different
      prefrontal areas depends on their co-operation with posterior associative
      cortices and subcortical brain structures such as the mediodorsal thalamic
      nucleus, hippocampus, amygdale and basal ganglia. Separate cortical and
      subcortical structures are included in functional networks which provide
      different aspects of the brain executive functions.

PMID- 25966573
TI  - [FMRI study of visual task switching in healthy individuals].
AB  - The present study was aimed, first, at developing a visual switching task for
      fMRI research and, second, at identification of the brain regions involved in
      task switching. Forty eight healthy individuals (from 21 to 56 years of age)
      participated in the study. The designed visual switching task was relatively
      short, it consisted of an easy stimulus set and involved a simple condition, in
      which participants had to shift their attention between two task conditions
      (classifying figures according to their form or number). Thus, this developed
      testing procedure can further be used to assess special populations, including
      patients with brain damage who cannot do monotonous tasks for a long period of
      time and have language impairments. The results of this testing technique
      revealed that task switching is carried out by an interconnected neuronal
      network, consisting of dorsolateral prefrontal cortex, inferior parietal area,
      secondary visual area, supplementary motor area and cerebellum cortex of both
      hemispheres.

PMID- 25966574
TI  - [EEG synchronisation in autistic children. Analysis of coherency].
AB  - EEG study of 5-7 years boys with autism revealed lower values of coherence in
      background delta, theta and alpha bands and higher values of coherence in
      background beta 1, beta 2 and gamma bands. Healthy boys showed higher values of
      beta and gamma coherence during cognitive task. Autistic persons demonstrated
      higher values of theta coherence during cognitive task.

PMID- 25966575
TI  - [Lateralized brain language semantic network demonstrated by word repetition
      suppression effect in MEG].
AB  - We studied auditory word repetition suppression effect using
      magnetoencephalography while subjects listened to "new" and "old" words whose
      familiarity they had to judge upon presentation. The lateralization of brain
      magnetic activity during processing of "new" and "old" words were estimated by
      computing RMS measure of whole-brain magnetic response within time window of
      semantic N400 (350-450 ms). A magnetic N400 was significantly stronger in the
      left than in the right hemisphere for the "new" words only. Repetition of "new"
      words led to sharp decrease of N400 response RMS in the left hemisphere but did
      not change right-hemispheric N400 RMS. The asymmetry index of this repetition
      suppression effect was lateralized to the left hemisphere for the majority of the
      participants and its magnitude was related to memory task performance. The
      findings point to a strong left-hemispheric dominance of word repetition
      suppression effect within the brain semantic networks at the level of whole
      network response.

PMID- 25966576
TI  - [Event-related synchronization/desynhronization during processing of target, no
      target and unknown visually presented words].
AB  - The aim of this investigation is to study neurophysiologic mechanisms of
      processing of relevant words and unknown words. Event-related
      synchronization/desynchronization during categorization of three types of stimuli
      (known targets, known no targets and unknown words) was examined. The main
      difference between known targets and unknown stimuli was revealed in the thetal
      and theta2 bands at the early stage after stimuli onset (150-300 ms) and in the
      delta band (400-700 ms). In the late time window at about 800-1500 ms thetal ERS
      in response to the target stimuli was smaller than to other stimuli, but theta2
      and alpha ERD in response to the target stimuli was larger than to known
      nontarget words.

PMID- 25966577
TI  - [Comparison of behavioral effects of fluoxetine, imipramine and new psychotropic
      drug TC-2153 on mice with hereditary predisposition to catalepsy].
AB  - Behavioral effects of classic antidepressants, fluoxetine and imipramine, and new
      psychotropic benzopentathiepin TC-2153 (20 mg/kg, per os) were studied on mice
      differing in the predisposition to catalepsy-noncataleptic AKR strain and
      cataleptic strains CBA and AKR.CBA-D13Mit76 (D13). Mice of D13 strain was created
      by transferring the CBA-allele of major locus of catalepsy to AKR genome. In the
      forced swim test (FST) fluoxetine showed antidepressant effect on mice of all
      three strains, imipramine was effective only in D13 mice, while TC-2153 produced
      antidepressant effect on AKR and D13 mice. Unlike to imipramine and fluoxetine,
      TC-2153 did not produce negative side effects in the open field and elevated plus
      maze tests. Thus, TC-2153 produces antidepressant effects similar to imipramine
      and fluoxetine, without any visible negative side effect on locomotory activity
      and anxiety. The D13 mice in the FST showed high sensitivity to the studied drugs
      in comparison to the parent strains and can be used as new genetic model for
      investigation of the mechanism of antidepressant effects.

PMID- 25966578
TI  - [Dynamics of spatial synchronization of epileptiform discharges in the rat
      neocortex].
AB  - Epileptiform potentials after the application of GABA A receptor antagonist first
      appeared in a local part of the cortex of anesthetized rats, and then with a
      small time lag appeared in other areas of the cortex. Externally, it looked like
      spreading. Potentials originally appeared at any point of recording, and then
      appeared (propagated) both in the rostral-caudal direction (forward) and
      reciprocally. The quantitative evaluation of this phenomenon showed that there
      are three periods of the epileptiform potential spreading. During the initial
      period, the epileptiform potentials appeared and spread relatively equally in
      rostrocaudal direction and backwards. In period 2 dominated potentials shift in
      rostrocaudal direction. After application of a sodium channel blocker epileptic
      activity significantly decreased. Frequency of initial appearance of potentials
      in the caudal areas increased. Propagation of the activity in one or another
      direction was observed. Obtained in this study quantitative characteristics of
      the initiation and spreading of epileptic activity suggest that in the cortex may
      exist independent generators, and distribution of the epileptiform potentials and
      the nature of this distribution implies that this process is based on direct and
      reciprocal functional connection of neurons.

PMID- 25966579
TI  - [Opine biosynthesis and catabolism genes of Agrobacterium tumefaciens and
      Agrobacterium rhizogenes].
AB  - Agrobacterium is a genus of soil bacteria with the ability to transform plant
      cells by a T-DNA-sequence located on the pTi/pRi- plasmid containing a set of
      genes expressed in plant cells. Expression of these genes leads to a
      proliferation of transformed cells, with the subsequent formation of tumors or
      growths of roots and the synthesis of opines--products of the condensation of
      amino acids with ketoacids or sugars used by Agrobacteria as a source of carbon
      and nitrogen. In this review, we systematized the information about most common
      opines in plant--Agrobacterium systems and their biosynthesis and catabolism
      genes, as well as the role of opines in the interaction of pathogenic
      Agrobacterium with plants and with other Agrobacterium strains, including the
      genetic consequences of such interactions.

PMID- 25966580
TI  - [Comparative analysis of natural and synthetic antimutagens as regulators of gene
      expression in human cells under exposure to ionizing radiation].
AB  - This paper studies the effect of plant peptides of thionine Ns-W2 extracted from
      seeds of fennel flower (Nigella sativa) and beta-purothionine from wheat germs
      (Triticum kiharae), as well as a synthetic antimutagen (crown-compound), on the
      expression of several genes involved in the.control of cellular homeostasis,
      processes of carcinogenesis, and radiation response in human rhabdomyosarcoma
      cells (RD cells), T-lymphoblastoid cell line Jurkat, and blood cells. All of
      these agents acted as antimutagens-anticarcinogens, reducing the expression of
      genes involved in carcinogenesis (genes of families MMP, TIMP, and IAP and G
      protein genes) in a tumor cell. A pronounced reduction in the mRNA level of these
      genes was caused by thionine Ns-W2, and the least effect was demonstrated by beta
      purothionine. Antimutagens had very little effect on the mRNA levels of the
      several studied genes in normal blood cells.

PMID- 25966581
TI  - [Inversion polymorphism of the nonbiting midges Camptochironomus pallidivittatus
      Edwards, 1929 (Diptera, Chironomidae) from populations of the Lower Volga region
      and Central Caucasus].
AB  - The karyotype of Camptochironomus pallidivittatus Edwards, 1929 (Diptera,
      Chironomidae) from five populations of the Lower Volga region and Central
      Caucasus (the northern macroslope) has been studied. In populations of S.
      pallidivittatus from the Central Caucasus, 11 banding sequences (BS) were found;
      one sequence, pal B10, was new to the species. In the Saratov population, 11 BS
      were also found, three of which were new for the species-pal A3, pal B11, and pal
      B12. The banding sequences detected for the first time have not yet been found in
      other parts of the habitat of this species and may be endemic to these regions.
      In the studied populations ofS. pallidivittatus, banding sequences were found
      that were nonstandard but fixed in the karyotype. This is indicative of some
      degree of chromosomal divergence. These banding sequences include pal A2.2 in arm
      A and pal B10.10 in arm B in the Central Caucasus region, as well as pal B2.2 and
      pal G2.2 in the Lower Volga region. Arms A, B, D, and G in the Central Caucasian
      populations and A, B, and D in the Saratov oblast were polymorphic. The
      composition of heterozygous sequences between populations from different regions
      coincided only in arm D (pal D 1.2). In arms A and B, the set of heterozygous BS
      was different: pal A1.2 and pal B1.10 sequences were found in the Central
      Caucasian populations, and pal A1.3 and B11.12 were found in Saratov oblast. The
      number of genotypic combinations of S. pallidivittatus was higher in the Central
      Caucasus region, whereas the number of zygotic combinations was higher in the
      Saratov population. The percentage of heterozygous larvae in the Central
      Caucasian populations varied from 20 to 80, whereas all individuals in the
      Saratov population had heterozygous inversions. Zygotic combinations of larvae in
      all the studied populations were different.

PMID- 25966582
TI  - [Chromosomal variation in Chironomus plumosus L. (Diptera, Chironomidae) from
      populations of Bryansk region, Saratov region (Russia), and Gomel region
      (Belarus)].
AB  - Cytogenetic analysis was performed on samples of Chironomus plumosus L. (Diptera,
      Chironomidae) taken from waterbodies of various types in Bryansk region (Russia)
      and Gomel region (Belarus). Karyotypes of specimens taken from stream pools of
      the Volga were used as reference samples. The populations of Bryansk and Gomel
      regions (except for a population of Lake Strativa in Starodubskii district,
      Bryansk region) exhibit broad structural variation, including somatic mosaicism
      for morphotypes of the salivary gland chromosome set, decondensation of telomeric
      sites, and the presence of small structural changes, as opposed to populations of
      Saratov region. As compared with Saratov and Bryansk regions, the Balbiani ring
      in the B-arm of chromosome I is repressed in populations of Gomel region. It is
      concluded that the chromosome set of Ch. plumosus in a range of waterbodies of
      Bryansk and Gomel regions is unstable.

PMID- 25966583
TI  - [Phylogenetic analysis of Pleurotus species].
AB  - We performed phylogenetic analysis for ten Pleurotus species, based on internal
      transcribed spacer (ITS) sequences of rDNA. A phylogenetic tree was constructed
      on the basis of 31 oyster fungi strains of different origin and 10 reference
      sequences from GenBank. Our analysis demonstrates that the tested Pleurotus
      species are of monophyletic origin. We evaluated the evolutionary distances
      between these species. Classic genetic analysis of sexual compatibility based on
      monocaryon (mon)-mon crosses showed no reproductive barriers within the P.
      cornucopiae-P. euosmus species complex. Thus, despite the divergence
      (subclustering) between commercial strains and natural isolates of P. ostreatus
      revealed by phylogenetic analysis, there is no reproductive isolation between
      these groups. A common allele of the matB locus was identified for the commercial
      strains Sommer and L/4, supporting the common origin of these strains.

PMID- 25966584
TI  - [Clonal micropropagation of a rare species Hedysarum theinum Krasnob (Fabaceae)
      and assessment of the genetic stability of regenerated plants using ISSR
      markers].
AB  - In the present study, a protocol was developed for the in vitro propagation of a
      rare medicinal plant, Hedysarum theinum (tea sweetvetch), from axillary buds, and
      identification of the regenerants was performed with the use of ISSR markers. It
      was demonstrated that Gamborg and Eveleigh medium supplemented with 5 MUM 6
      benzylaminopurine was the best for H. theinum for initial multiplication. On the
      other hand, half-strength Murashige and Skoog (MS) basal medium supplemented with
      7 MUM alpha-naphthaleneacetic acid proved to be the best for explant rooting.
      Molecular genetic analysis of the H. theinum mother plants and the obtained
      regenerants was performed with six ISSR markers. Depending on the primer, four to
      ten amplified fragments with sizes ranging from 250 to 3000 bp were identified.
      Our results confirmed the genetic stability of regenerants obtained in five
      passages and their identity to the mother plant.

PMID- 25966585
TI  - [New SNP markers of the honeybee vitellogenin gene (Vg) used for identification
      of subspecies Apis mellifera mellifera L].
AB  - Preservation of the gene pool of honeybee subspecies Apis mellifera mellifera is
      of vital importance for successful beekeeping development in the northern regions
      of Eurasia. An effective method of genotyping honeybee colonies used in modern
      science is the mapping of sites of single nucleotide polymorphism (SNP). The
      honeybee vitellogenin gene (Vg) encodes a protein that affects reproductive
      function, behavior, immunity, longevity, and social organization in the honeybee
      Apis mellifera and is therefore a topical research subject. The results of
      comparative analysis of honeybee Vg sequences show that there are 26 SNP sites
      that differentiate M and C evolutionary branches and can be used as markers in
      selective breeding, DNA-barcoding, and the creation of genetic passports for A.
      m. mellifera colonies.

PMID- 25966586
TI  - [Mitochondrial DNA sequence variation, demographic history, and population
      structure of Amur sturgeon Acipenser schrenckii Brandt, 1869].
AB  - The variability of the mtDNA control region (D-loop) was examined in Amur
      sturgeon endemic to the Amur River. This species is also classified as critically
      endangered by the IUCN Red List of Threatened species. Sequencing of 796- to 812
      bp fragments of the D-loop in 112 sturgeon collected in the Lower Amur revealed
      73 different genotypes. The sample was characterized by a high level of
      haplotypic (0.976) and nucleotide (0.0194) diversity. The identified haplotypes
      split into two well-defined monophyletic groups, BG (n = 39) and SM (n = 34),
      differing (HKY distance) on average by 3.41% of nucleotide positions upon an
      average level of intragroup differences of 0.54 and 1.23%, respectively.
      Moreover, the haplotypes of the SM groups differed by the presence of a 13-14 bp
      deletion. Most ofthe samples (66 out of 112) carried BG haplotypes. Overall, the
      pattern of pairwise nucleotide differences and the results of neutrality tests,
      as well as the results of tests for compliance with the model of sudden
      demographic expansion or with the model of exponential growth pointed to a past
      significant increase in the number of Amur sturgeon, which was most clearly
      manifested in the analysis of data on the BG haplogroup. The constructed Bayesian
      skyline plots showed that this growth began about 18 to 16 thousand years ago. At
      present, the effective size of the strongly reduced (due to overharvesting)
      population of Amur sturgeon may be equal to or even lower than it was before the
      beginning of this growth during the Last Glacial Maximum. The presence in the
      mitochondrial gene pool ofAmur sturgeon of two haplogroups, their unequal
      evolutionary dynamics, and, judging by scanty data, their unequal representation
      in the Russian and Chinese parts of the Amur River basin point to the possible
      existence of at least two distinct populations of Amur sturgeon in the past.

PMID- 25966587
TI  - [Phylogeography and phenotypic diversity of the pumpkinseed Sunfish Lepomis
      gibbosus (Linnaeus, 1758) of the Northern Black Sea Coast].
AB  - This paper studies the origin and the genetic and morphological diversity of the
      pumpkinseed sunfish, a North American invader that is actively expanding its
      range in the Northern Black Sea Coast. Based on an analysis of variability of the
      nucleotide sequence of the mtDNA cyt b locus, it was found that all populations
      of the Northern Black Sea Coast (basins of Dnieper, Dniester, and Danube rivers)
      are represented by one haplotype. Intraspecific variability is absent.
      Phylogeographic analysis revealed that the most related haplotype is in a
      population of pumpkinseed sunfish from New Germany Lake in the Potomac Riverbasin
      (Maryland, United States), which makes it possible to consider it a parent of the
      investigated populations. Morphological variation oin countable traits was highly
      homogeneous. Significant differentiation of a sample from the population of the
      Dnieper Reservoir from the populations of the Danube and Dniester was found for
      plastic traits of both the body and cranium. Analysis of the trajectories of
      development showed that the Dnieper is inhabited by a "pelagic" morpho-ecological
      form of pumpkinseed sunfish, while the Dniester and Danube is inhabited by a
      "littoral" form. It is suggested that the success of the settlement of this North
      American species in the Northern Black Sea Coast does not depend on the origin or
      the level of its genetic diversity but is instead likely to be ensured by the
      realization of its available discrete morpho-ecological variability.

PMID- 25966588
TI  - [Replicative study of susceptibility to childhood-onset schizophrenia in
      Kazakhs].
AB  - This paper reports the results of replicative analysis of associations of 15 SNPs
      in a region of 14 genes previously identified in genome-wide association studies
      (GWAS) with early-onset schizophrenia in Kazakhs. An association of early-onset
      schizophrenia with genetic markers in three genes (VRK2, KCNB2, and CPVL) was
      found. An association of rs2312147 in the VRK2 gene with schizophrenia was also
      previously reported in the Chinese population, so this marker may be considered
      as possibly race-specific. Two groups consisting of four and six genes
      demonstrating intergenic epistatic interactions were revealed by multifactor
      dimensionality reduction methods. The gene ontologies of 14 studied genes were
      reduced to variants of one molecular function (peptidase activity) and one
      biological process (positive regulation of biosynthesis processes). Bioinformatic
      analysis of the protein-protein interactions of products of the genes under study
      demonstrates that the products of six out of 14 genes may be involved in a single
      interrelated network, the major connecting link of which is represented by their
      ubiquitination by the UBC protein.

PMID- 25966589
TI  - [Association of (192) Q>R polymorphism of the paraoxonase gene with a lipid
      profile and components of lipid peroxidation and antioxidant protection in
      populations of Russians and Buryats from Eastern Siberia].
AB  - The distribution of genotypes and alleles of Q192R polymorphism of the
      paraoxonase1 (rs622) gene was studied in Russian and Buryat populations living in
      Eastern Siberia. Correlations between genotypes and some parameters of the lipid
      profile and lipid peroxidation indicators were revealed. In the group of
      Russians, the frequency of genotypes was QQ-0.354; QR-0.569 and RR-0.077, alleles
      Q-0.638, and R-0.362. In the group of Buryats, the genotype frequencies were QQ
      0.204; QR-0.629 and RR-0.167, alleles Q-0.518, and R-0.482. No differences in
      allele and genotype frequencies were established between the groups of Russians
      and Buryats. In the group of Russians, the VLD L cholesterol content (H = 6.461;
      p = 0.0395) and diene conjugates (H = 8.107; p = 0.0174) was higher in carriers
      of genotype QQ than in carriers of genotype RR. In the group of Buryats, the HDL
      cholesterol content (H = 1.548; p = 0.0461) was higher in carriers of genotype
      QQ, wherein the concentration of malondialdehyde (H = 13.854, p = 0.0010) was
      lower in comparison with carriers of genotype RR.

PMID- 25966590
TI  - [Association between serotonin receptor 2C gene Cys23Ser polymorphism and social
      behavior in schizophrenia patients and healthy individuals].
AB  - The purpose of this work was to search for associations between the serotonin
      receptor 2C gene (HTR2C) and the peculiarities of social behavior and social
      cognition in schizophrenia. To do this, patients with schizophrenia spectrum
      disorders and healthy control subjects were genotyped for the Cys23Ser HTR2C
      marker and underwent psychological examination, including assessment of
      Machiavellianism, recognition of emotions in facial expression, and theory of
      mind. In addition, we estimated the trait anxiety level as a potential factor
      affecting the relationship between the gene HTR2C and social behavior. We found a
      significant association between the Ser allele and a reduction of estimates on
      the Mach-LV Machiavellianism scale in the total sample of patients (n = 182) and
      control subjects (n = 189), which did not reach the confidence level in either of
      the groups. A tendency towards a HTR2C gene influence on the trait anxiety level
      was also revealed. The association between HTR2C and Machiavellianism was
      retained if the anxiety level was taken into account. The results suggest a
      pleiotropic effect of HTR2Con anxiety and Machiavellianism.

PMID- 25966591
TI  - [Association of polymorphic variants of FTO and MC4R genes with obesity in a
      Tatar population].
AB  - Obesity is a chronic relapsing disease that leads to numerous ailments and
      requires lifelong treatment. Genetic predisposition is one of the mostly
      discussed aspects of obesity development, and genome-wide association studies
      have provided evidence that several variants of the FTO and MC4R genes are
      significantly associated with obesity. In this study the association of FTO
      (rs9939609, rs7202116, and rs9930506) and MC4R (rs12970134 and rs17782313) genes'
      SNPs with obesity in Tatar women has been analyzed. In the investigation 340
      women with obesity (Body Mass Index (BMI) >= 30 kg/m2) and 330 women from a
      control group (BMI up to 24.9 kg/m2) took part. The FTO rs9939609 (p = 0.0002)
      and rs9930506 (p = 0.0005) SNPs were shown to be associated with obesity risk
      following an additive model, while the MC4R rs12970134 (p = 0.0076) and rs1778231
      (p = 0.021) SNPs were associated by a recessive model. We also showed an
      association of quantitative parameters (age, weight, and BMI) with two the FTO
      rs9939609 and rs9930506 SNPs and the association of age and the MC4R rs12970134
      SNP. Our study demonstrates the role of genetic variability in FTO and MC4R genes
      in obesity development in Tatar women from Russia.

PMID- 25966592
TI  - [The combined effect of E298D polymorphism of the endothelial nitric oxide
      synthase gene and smoking on the risk of cerebral stroke].
AB  - Violations of the endothelium-dependent regulation of cerebral vessel tone are an
      important link in the pathogenesis of cerebrovascular disorders. The purpose of
      this study was to investigate the association of--86T>C and E298D polymorphisms
      of the endothelial nitric oxide synthase(NOS3) gene with the risk of ce-ebral
      stroke (CS) in Russian inhabitants of Central Russia, as well as to evaluate the
      trigger effect of smoking on the risk of CS in carriers of genotypes NOS3.
      Genotyping of-786T>C and E298D polymorphisms of the NOS3 gene was carried out
      through real time. CR and TaqMan allele discrimination assays. It was deter-ined
      that the genotype 298DD is associated with the risk of CS (OR =-1.71, 95% CII=
      1.05-2.78, P= 0.03). Subsequent analysis showed that genotype 298 DD (OR = 3.75;
      95% CII= 1.39-10.11; P= 0.01) is associatedw ith an increased risk of CS
      exclusively in smoking individuals. The combination ofg enotypes -786T/Cx298D/D
      was associated with the risk of CS. n smokers (OR = 7.71; 95% CI = 1.31-45.34; P
      = 0.02). In the present study, it was found that smoking is a significant
      modifying risk factor for cerebral stroke in the carriers of the 298DD and 
      786T/C. enotypes of endothelial nitric oxide synthase.

PMID- 25966593
TI  - [Knockdown of InR gene in ventral nephrocytes promotes resistance to toxic stress
      in Drosophila melanogaster females].
AB  - Hemolymph filtration in insects is performed by nephrocytes, additional cells of
      the circulatory system that are not connected to Malpighian vessels. Drosophila
      has two types of nephrocytes: the ventral ("garland"), which are situated around
      the connection site of the esophagus and proventriculus, and the pericardial,
      which are localized around the heart. In this study, we examined the role of the
      of insulin-like receptor (InR)gene in regulation of the function of ventral
      nephrocytes (VNC) in D. melanogaster females. Immunofluorescent analysis of
      female VNC with anti-InR antibodies revealed for the first time that the InR gene
      is expressed in VNC cells. To determine whether a change in the level of InR
      expression has an effect on VNC function in Drosophila females, we implemented an
      antisense suppressor of the InR gene, together with a driver that is expressed
      specifically in VNC. VNC function was evaluated by survival of the females
      exposed to toxic stress (treatment with AgNO3). This study has shown for the
      first time that suppression of InR expression in VNC leads to a rise in the
      survival of flies under conditions of toxic stress.

PMID- 25966594
TI  - [LEP gene allelic polymorphism in a subpopulation of Ayrshire cattle].
AB  - Genotyping of the leptin gene locus (LEP) (SNP: R25C, Y7F, and A80V) has been
      conducted in cows from two cattle droves (n = 106 and n = 34) and in bulls of
      Ayrshire cattle (n = 9) that are intensively used at present for artificial
      insemination in cows in Krasnodar krai. The absence of A80V polymorphism (C --> T
      at position 95691973 bp of leptin gene) has been established in the genotypes of
      Ayrshire cattle as compared to Holstein cattle; however, the F allele (Y7F site A
      --> T at position 95689996 bp of LEP gene), which is rare in Holstein cattle, was
      shown to be frequent in Ayrshire cows and producer bulls (with a frequency of
      0.22-0.79). The heterozygosity did not exceed 0.11 in adult animals, which might
      be evidence of a decreased vitality in animals bearing the FF genotype. Moreover,
      the CC genotype (R25C site T-C at position 95690050 bp of LEP gene) was revealed
      to be linked to the YY genotype (Y7F site) in 97% of cases from possible
      combinations of the CCYY, CCYF, and CCFF genotypes, while the FF genotype (Y7F
      site) was observed to be linked to the RR genotype (R25C site) in 100% of cases
      of possible combinations of FFCC, FFRC, and FFRR genotypes.

PMID- 25966595
TI  - [Mammalian cell culture as a model for studying the intracellular traffic of
      densovirus proteins].
AB  - The intracellular localization of the fusion protein composed of green
      fluorescent protein (GFP) and one of the capsid proteins (namely VP1) of the
      German cockroach densovirus BgDV1 was investigated using the HeLa human cell
      culture. The intracellular localization of GFP was analyzed in a series of
      control experiments. Histochemical analysis with GFP antibodies showed that the
      fusion protein is localized exclusively inside the nucleus of cells because of
      the transitory expression of the corresponding vector constructions, whereas the
      GFP is located both in the nucleus and the cytoplasm. We can conclude that the
      signal of the nuclear localization of the capsid protein of the German cockroach
      densovirus is functionally active, not only within the cells of this insect but
      within the human cell culture as well. This observation extends the experimental
      possibilities for studying the genetic control of intracellular traffic of
      densovirus proteins.

PMID- 25966596
TI  - Combatting prescription drug abuse--AMS efforts.

PMID- 25966597
TI  - Show me the numbers.

PMID- 25966598
TI  - Hepatitis C in Arkansas: updates on epidemiology, testing and treatment.
AB  - Hepatitis C infection is the most common blood-borne infection in the United
      States with an estimated 2.7 million individuals suffering from chronic
      infection. Of those who are infected with Hepatitis C virus, 75-85% develop
      chronic infection. Without treatment for chronic infection, individuals can
      develop liver diseases, such as cirrhosis and hepatocellular carcinoma, during
      many years of asymptomatic infection. To examine the burden of Hepatitis C virus
      infection in the state, the Arkansas Department of Health created an
      epidemiologic profile based on data collected in 2013 from several data sources,
      including the department's Hepatitis C surveillance program. In order to make
      more Arkansans aware of their infection, the local health units in all 75
      counties of the state recently began screening individuals at risk for the
      disease, including persons born during the years 1945-1965. Despite recent
      advances in treatment efficacy, identifying infected individuals and connecting
      patients to affordable HCV treatment and care remain priorities.

PMID- 25966599
TI  - Newborn screening improvements in Arkansas.

PMID- 25966600
TI  - Diagnosis and successful surgical management of posterior nutcracker syndrome in
      a patient with loin pain hematuria.
AB  - The syndrome of loin pain hematuria in the absence of stones is poorly understood
      but must be considered in the differential diagnosis for patients with clinical
      manifestations resembling nephrolithiasis. A 22-year-old white female with a 4
      year history of left flank pain and hematuria underwent an extensive workup with
      normal renal ultrasound and cystourethroscopies. CT scan and MRI revealed a retro
      aortic left renal vein. Posterior nutcracker syndrome was considered the most
      likely diagnosis. The patient underwent a left laparoscopic nephrectomy with auto
      transplantation in the right iliac fossa. She developed azotemia shortly after,
      which resolved and since then has become asymptomatic.

PMID- 25966601
TI  - The culture of complexion: the impacts of society's role in shaping the
      definition of beauty.
AB  - The definition of beauty has evolved as the trends valued by the top of society
      change. For centuries, fair skin was a requirement of the Western definition of
      beauty; however, a shift in the 1920s made tanned skin the new standard. In this
      article, smoking and tanning are presented as risky behaviors that are
      perpetuated through industry advertising and exploitation of the authority of
      health professionals. The article further explores the culture of complexion in
      Western society before and after the 1920s as well as the consequences of tanning
      and efforts to rewrite society's definition of beauty.

PMID- 25966602
TI  - The pharmaceutical use of Lapis Lazuli in the Ancient East.

PMID- 25966603
TI  - 'What the Dickens!' The out-patients pharmacy at the Middlesex Hospital, London.

PMID- 25966604
TI  - Knowledge of burn wound healing: the heritage from traditional pharmacy of
      Persia.
AB  - The traditional pharmacy of Persia is based on numerous ancient manuscripts
      written by the elites of medicine and pharmacy. These references which belong to
      different centuries (mostly from the 9th to 19th century) represent vast
      information about pharmaceutical and therapeutic knowledge. Studying these works
      could be valuable in revealing the hidden parts of the history of science,
      especially pharmacy and medicine. Also, modernisation of the methods of treatment
      and the majority of formulations seems to be possible. It is obvious that setting
      ancient experiences besides recent studies makes pharmacists and physicians more
      powerful. This review aims to introduce traditional knowledge about different
      treatments for burn wounds which has been extracted from various Persian
      manuscripts.

PMID- 25966605
TI  - The Pars Collection: a window into the past.

PMID- 25966606
TI  - Armenian bole: a historical medicinal clay.
AB  - The medical use of earths and minerals is probably as old as the history of
      mankind. Particular types of clays and earths are still being used worldwide as
      therapeutic agents in the folk medicine of different countries. From the 19th
      century, the medicaments included in countries' pharmacopeias whose exact
      pharmacological activity or the chemistry of their active components was not
      known gradually decreased in number, despite their popularity among patients.
      With today's analytical armamentarium it may be time to reconsider returning some
      of those compounds to pharmacopeias. By using modern techniques in the past two
      decades, researchers have studied the active components of healing clays and
      their pharmacological properties. Many of them possess valuable therapeutic
      properties which could be used in modern medicine in pharmaceutical dosage forms.
      Our knowledge about the medical substances that our ancestors used through
      centuries could be used today as an evidence base for further clinical and
      pharmacological research. One of these substances is Armenian bole. In this work
      we studied the historical perspective of its therapeutic use in different
      countries. Also a sample sold in the market in Iran was purchased and X-ray
      diffraction analysis was performed on it to find out its chemical composition.

PMID- 25966607
TI  - An unusual dihydrobenzofuroisocoumarin and ent-kaurane diterpenoids from Pteris
      multifida.
AB  - An unusual 5-C-methylated-dihydrobenzofuroisocoumarin, named multifidarin A (1),
      and two new ent-kaurane diterpenoids, named multikauranes A (2) and B (3),
      together with three known ent-kaurane diterpenoids, were isolated from the whole
      plants of Pteris multifida. The structures of 1-3 were elucidated by
      spectroscopic methods. The cytotoxic activities of all new compounds were
      evaluated against five human tumor cell lines. A possible biosynthetic process
      for the formation of 1 is proposed. 

PMID- 25966608
TI  - Resuscitating preterm infants with 100% oxygen is associated with higher
      oxidative stress than room air.
AB  - AIM: The starting fraction of inspired oxygen for preterm resuscitation is a
      matter of debate, and the use of room air in full-term asphyxiated infants
      reduces oxidative stress. This study compared oxidative stress in preterm infants
      randomised for resuscitation with either 100% oxygen or room air titrated to
      internationally recommended levels of preductal oxygen saturations. METHODS:
      Blood was collected at birth, two and 12 hours of age from 119 infants <32 weeks
      of gestation randomised to resuscitation with either 100% oxygen (n = 60) or room
      air (n = 59). Oxidative stress markers, including advanced oxidative protein
      products (AOPP) and isoprostanes (IsoP), were measured with high-performance
      liquid chromatography and mass spectrometry. RESULTS: Significantly higher levels
      of AOPP were found at 12 hours in the 100% oxygen group (p < 0.05). Increases
      between two- and 12-hour AOPP (p = 0.004) and IsoP (p = 0.032) concentrations
      were significantly higher in the 100% oxygen group. CONCLUSION: Initial
      resuscitation with room air versus 100% oxygen was associated with lower protein
      oxidation at 12 hour and a lower magnitude of increase in AOPP and IsoP levels
      between two and 12 hours of life. Correlations with clinical outcomes will be
      vital to optimise the use of oxygen in preterm resuscitation.

PMID- 25966609
TI  - Bioaccessibility of the Bioactive Peptide Carnosine during in Vitro Digestion of
      Cured Beef Meat.
AB  - A bioactive compound is a food component that may have an impact on health. Its
      bioaccessibility, defined as the fraction released from the food matrix into the
      gastrointestinal tract during digestion, depends on compound stability,
      interactions with other food components, and supramolecular organization of food.
      In this study, the effect of pH on the bioaccessibility of the bioactive
      dipeptide carnosine was evaluated in two commercial samples of the Italian cured
      beef meat bresaola at two key points of digestion: before the gastric and after
      the duodenal phases. The digestion process was simulated using an in vitro static
      system, whereas capillary zone electrophoresis (CZE) and (1)H nuclear magnetic
      resonance (NMR) were used for quantitative analysis. The gap between the total
      carnosine content, measured by CZE, and its free diffusible fraction observable
      by NMR spectroscopy, was 11 and 19% for two independent bresaola products, where
      such percentages represent the fraction of carnosine not accessible for
      intestinal absorption because it was adsorbed to the food matrix dispersed in the
      digestion fluid. 

PMID- 25966610
TI  - ANZSGM Annual Scientific Meeting 2015: 6-8 May 2015, The Pan Pacific Hotel, Perth
      WA.

PMID- 25966611
TI  - Welcome message.

PMID- 25966612
TI  - Prizes.

PMID- 25966613
TI  - Committee structure.

PMID- 25966614
TI  - Abstracts of the Australian and New Zealand Society for Geriatric Medicine Annual
      Scientific Meeting, 6-8 May 2015, Pan Pacific Hotel, Perth, WA, Australia.

PMID- 25966615
TI  - Glio-vascular changes during ageing in wild-type and Alzheimer's disease-like
      APP/PS1 mice.
AB  - Vascular and glial involvement in the development of neurodegenerative disorders,
      such as Alzheimer's disease (AD), and age-related brain vulnerabilities have been
      suggested. Therefore, we sought to: (i) investigate which vascular and glial
      events are evident in ageing and/or AD, (ii) to establish the temporal evolution
      of vascular and glial changes in AD-like and wild-type (WT) mice and (iii) to
      relate them to amyloid-beta (Abeta) peptide accumulation. We examined
      immunohistochemically hippocampi and cortex from APP/PS1dE9 and WT C57BL/6 mice
      along ageing and disease progression (young-adulthood, middle- and old-age).
      Ageing resulted in the increase in receptor for advanced glycation endproducts
      expression, as well as the entrance of thrombin and albumin in hippocampal
      parenchyma. In contrast, the loss of platelet-derived growth factor receptor-beta
      (PDGFR-beta) positive cells, in both regions, was only related to AD
      pathogenesis. Hypovascularization was affected by both ageing and AD in the
      hippocampus, but resulted from the interaction between both factors in the
      cortex. Astrogliosis was a result of AD in hippocampus and of both factors in
      cortex, while microgliosis was associated with fibrillar amyloid plaques in AD
      like mice and with the interaction between both factors in each of the studied
      regions. In sum, these data show that senile plaques precede vascular and glial
      alterations only in hippocampus, whereas in cortex, vascular and glial
      alterations, namely the loss of PDGFR-beta-positive cells and astrogliosis,
      accompanied the first senile plaques. Hence, this study points to vascular and
      glial events that co-exist in AD pathogenesis and age-related brain
      vulnerabilities.

PMID- 25966616
TI  - Hippocampal GABAergic interneurons coexpressing alpha7-nicotinic receptors and
      connexin-36 are able to improve neuronal viability under oxygen-glucose
      deprivation.
AB  - The hippocampal interneurons are very diverse by chemical profiles and rather
      inconsistent by sensitivity to CI. Some hippocampal GABAergic interneurons
      survive certain time after ischemia while ischemia-sensitive interneurons and
      pyramidal neurons are damaged. GABAergic signaling, nicotinic receptors
      expressing alpha7-subunit (alpha7nAChRs(+)) and connexin-36 (Cx36(+),
      electrotonic gapjunctions protein) contradictory modulate post-ischemic
      environment. We hypothesized that hippocampal ischemia-resistant GABAergic
      interneurons coexpressing glutamate decarboxylase-67 isoform (GAD67(+)),
      alpha7nAChRs(+), Cx36(+) are able to enhance neuronal viability. To check this
      hypothesis the histochemical and electrophysiological investigations have been
      performed using rat hippocampal organotypic culture in the condition of 30-min
      oxygen-glucose deprivation (OGD). Post-OGD reoxygenation (4h) revealed in CA1
      pyramidal layer numerous damaged cells, decreased population spike amplitude and
      increased pair-pulse depression. In these conditions GAD67(+) interneurons
      displayed the OGD-resistance and significant increase of GABA
      synthesis/metabolism (GAD67-immunofluorescence, mitochondrial activity). The
      alpha7nAChRs(+) and Cx36(+) co-localizations were revealed in resistant GAD67(+)
      interneurons. Under OGD: GABAA-receptors (GABAARs) blockade increased cell damage
      and exacerbated the pair-pulse depression in CA1 pyramidal layer; alpha7nAChRs
      and Cx36-channels separate blockades sufficiently decreased cell damage while
      interneuronal GAD67-immunofluorescence and mitochondrial activity were similar to
      the control. Thus, hippocampal GABAergic interneurons co-expressing alpha7nAChRs
      and Cx36 remained resistant certain time after OGD and were able to modulate CA1
      neuron survival through GABAARs, alpha7nAChRs and Cx36-channels activity. The
      enhancements of the neuronal viability together with GABA synthesis/metabolism
      normalization suggest cooperative neuroprotective mechanism that could be used
      for increase in efficiency of therapeutic strategies against post-ischemic
      pathology.

PMID- 25966617
TI  - A population-based study elicits a reverse correlation between age and overall
      survival in elderly patients with rectal carcinoma receiving adjuvant
      chemotherapy.
AB  - Colorectal cancer is the third most common cancer and the fourth most common
      cause of cancer-related death globally. This population-based study aimed to
      explore the predictive factors that affected the overall survival of rectal
      cancer patients receiving adjuvant chemotherapy plus radical surgery using a Cox
      proportional hazards modeling approach. A total of 619 patients with rectal
      cancer who underwent surgery were enrolled between October 2006 and May 2013.
      Clinical characteristics of the patients were compared among the groups and
      potential prognostic factors were analyzed using the spss program, version 19.0.
      Patients aged >= 70 years have distinctive characteristics such as lager tumour
      size (>= 5 cm), damaged micturition and higher incidence of diabetes compared to
      younger and middle-aged patients. Male gender, tumour size (>= 5 cm), poor
      differentiation, later stage, adjuvant chemotherapy, damaged micturition,
      hypertension or diabetes are associated with a worse prognosis for rectal cancer
      patients (P < 0.05). However, smoking is a favourable factor to the patients (P =
      0.018). Age of >= 70 years is an independent prognostic factor for patients with
      rectal cancer after surgery (P = 0.000) and elderly patients with Stage II and
      III disease receiving adjuvant chemotherapy show a favourable prognosis. The
      elderly patients who suffered from diabetes receiving adjuvant chemotherapy have
      a poor prognosis. Further prospective and large population studies are warranted
      to confirm the findings of this study.

PMID- 25966618
TI  - IS256 abolishes gelatinase activity and biofilm formation in a mutant of the
      nosocomial pathogen Enterococcus faecalis V583.
AB  - Enterococcus faecalis is one of the most controversial species of lactic acid
      bacteria. Some strains are used as probiotics, while others are associated with
      severe and life-threatening nosocomial infections. Their pathogenicity depends on
      the acquisition of multidrug resistance and virulence factors. Gelatinase, which
      is required in the first steps of biofilm formation, is an important virulence
      determinant involved in E. faecalis pathogenesis, including endocarditis and
      peritonitis. The gene that codes for gelatinase (gelE) is controlled by the Fsr
      quorum-sensing system, whose encoding genes (fsrA, fsrB, fsrC, and fsrD) are
      located immediately upstream of gelE. The integration of a DNA fragment into the
      fsr locus of a derived mutant of E. faecalis V583 suppressed the gelatinase
      activity and prevented biofilm formation. Sequence analysis indicated the
      presence of IS256 integrated into the fsrC gene at nucleotide position 321.
      Interestingly, IS256 is also associated with biofilm formation in Staphylococcus
      epidermidis and Staphylococcus aureus. This is the first description of an
      insertion sequence that prevents biofilm formation in E. faecalis. 

PMID- 25966619
TI  - The effect of secondary cholestasis on the CD68-positive and CD163-positive
      macrophage population, cellular proliferation, and apoptosis in rat testis.
AB  - The pathogenesis of hypogonadism in male patients with cirrhosis is complex and
      not well explained. Systemic infection and inflammation can inhibit testicular
      functions of endocrine and spermatogenesis. The acute inflammation induced by
      lipopolysaccharide can cause testicular acute inflammation. Both clinical and
      animal experimental data indicate that the developing process of
      cholestasis/cirrhosis can lead to endotoxemia. Little is known about the long
      term effects of cholestasis on the intratesticular macrophage population,
      cellular proliferation and apoptosis. A rat model of secondary cholestasis caused
      by common bile duct ligation (CBDL) was used to evaluate the impact of
      cholestasis on them, and the influence of biliary decompression
      (choledochoduodenostomy). Endotoxemia occurred in animals at 20 days CBDL
      (20dCBDL) and 30 days CBDL (30dCBDL), but disappeared after 30 days biliary
      decompression in rats with CBDL. There was a considerable increase in the numbers
      of intratesticular CD68(+) and CD163(+) macrophages following CBDL. After biliary
      decompression, CD68(+) macrophage numbers decreased, but remained higher than
      that of controls; meanwhile, CD163(+) remained elevated only in rats with
      30dCBDL. After CBDL, there was a progressive decrease in the expression of Bcl-2
      protein and in proliferating cell nuclear antigen (PCNA(+)) cells, and a dramatic
      increase in the expression of Bax, active caspase-3 and apoptotic cells. These
      data suggest that secondary cholestasis expands the population of CD68(+) and
      CD163(+) macrophages in the testicular interstitium, decreases testicular
      proliferative activity, and promotes testicular apoptosis, which may be one of
      the mechanisms of biliary cirrhosis-related hypogonadism. 

PMID- 25966620
TI  - Glucagon-Like Peptide-1 Receptor Activation Does not Affect Re-Endothelialization
      but Reduces Intimal Hyperplasia via Direct Effects on Smooth Muscle Cells in a
      Nondiabetic Model of Arterial Injury.
AB  - Diabetic patients have an increased risk of restenosis and late stent thrombosis
      after angioplasty, i.e. complications that are related to a defective re
      endothelialization. Exendin-4, a stable glucagon-like peptide (GLP)-1 receptor
      agonist, has been suggested to influence the formation of intimal hyperplasia and
      to increase endothelial cell proliferation in vitro. Thus, the aim of this study
      was to investigate the mechanisms by which treatment with exendin-4 could
      influence re-endothelialization and intimal hyperplasia after vascular injury.
      METHODS: Sprague-Dawley rats were subjected to balloon injury of the left common
      carotid artery and treated for 4 weeks with exendin-4 or vehicle. Intimal
      hyperplasia and vessel wall elasticity were monitored noninvasively by high
      frequency ultrasound, and re-endothelialization was evaluated upon sacrifice
      using Evans blue dye. RESULTS AND CONCLUSION: Exendin-4 selectively reduced the
      proliferation of smooth muscle cells (SMCs) and intimal hyperplasia in vivo
      without affecting the re-endothelialization process, but treatment with exendin-4
      improved arterial wall elasticity. Our data also show that exendin-4
      significantly decreased the proliferation and increased the apoptosis of SMCs in
      vitro, effects that appear to be mediated through cAMP signaling and endothelial
      nitric oxide synthase following GLP-1 receptor activation. Together, these
      effects of exendin-4 are highly desirable and may lead to an improved outcome for
      patients undergoing vascular interventions.

PMID- 25966621
TI  - Diagnostic value of frequency-associated vestibular-evoked myogenic potential
      responses in Meniere's disease.
AB  - Thirty subjects with unilateral Meniere's disease (MD) and 18 age-matched
      controls underwent cervical (cVEMP) and ocular vestibular-evoked myogenic
      potential (oVEMP) testing using bilateral air-conducted stimulation (ACS) with
      stimulus frequencies of 500 and 1,000 Hz. The aim of this study is to determine
      the diagnostic value of frequency-associated responses in MD using oVEMP and
      cVEMP following 500- and 1,000-Hz ACS. In healthy controls and unaffected ears,
      responses to 500 Hz were found better than 1,000-Hz ACS in both oVEMP and cVEMP,
      while ears with MD responded to 1,000-Hz ACS better than to 500-Hz ACS in oVEMP.
      In cVEMP tests, affected ears responded to 500-Hz and 1,000-Hz ACS equally.
      Amplitude ratios of 1,000/500 Hz in both oVEMP and cVEMP were successful in
      differing affected ears from unaffected ears and healthy controls. This study
      showed frequency alteration of oVEMP and cVEMP can be used as a diagnostic test
      battery in MD.

PMID- 25966622
TI  - Applying developmental programming to clinical obstetrics: my ward round.
AB  - The theory of developmental programming is supported by accumulating evidence,
      both observational and experimental. The direct application of the principles of
      developmental programming by clinicians to benefit pregnant women remains an area
      of limited attention. Examining a selection of inpatients at an obstetric
      referral center, I searched for situations in which clinical decision making
      could be driven by the principles of developmental programming. I also looked for
      situations in which the clinical research agenda could be dictated by these
      concepts. In the decision to undertake preventive measures to avoid preeclampsia,
      the offspring's perspective may support more liberal application of calcium and
      aspirin. Consideration of the long-term health perspective of the offspring could
      drive choices in the management of obesity and diabetes in pregnancy. The
      administration of corticosteroids in women delivering by elective cesarean at
      term may have modest short-term benefits, but additional trials are necessary to
      investigate long-term offspring health. The offspring of women suffering
      hyperemesis gravidarum may benefit from nutritional therapy. The long-term health
      of the offspring could affect couples' choice for IVF or expectant management.
      Applying the principles of developmental programming to the management of
      pregnant women could drive clinical decision making and is driving the clinical
      research agenda. Increasingly, developmental programming concepts are becoming an
      integral part of clinical practice, as well as determining the choice of outcomes
      in trials in obstetrics and fertility medicine. The presented cases underscore
      the need for more research to guide clinical practice. 

PMID- 25966623
TI  - Overall rate, location, and predictive factors for positive surgical margins
      after robot-assisted laparoscopic radical prostatectomy for high-risk prostate
      cancer.
AB  - We report the overall rate, locations and predictive factors of positive surgical
      margins (PSMs) in 271 patients with high-risk prostate cancer. Between April 2008
      and October 2011, we prospectively collected data from patients classified as
      D'Amico high-risk who underwent robot-assisted laparoscopic radical
      prostatectomy. Overall rate and location of PSMs were reported. Stepwise logistic
      regression models were fitted to assess predictive factors of PSM. The overall
      rate of PSMs was 25.1% (68 of 271 patients). Of these PSM, 38.2% (26 of 68) were
      posterolateral (PL), 26.5% (18 of 68) multifocal, 16.2% (11 of 68) in the apex,
      14.7% (10 of 68) in the bladder neck, and 4.4% (3/68) in other locations. The PSM
      rate of patients with pathological stage pT2 was 8.6% (12 of 140), 26.6% (17 of
      64) of pT3a, 53.3% (32/60) of pT3b, and 100% (7 of 7) of pT4. In a logistic
      regression model including pre-, intra-, and post-operative parameters, body mass
      index (odds ratio [OR]: 1.09; 95% confidence interval [CI]: 1.01-1.19, P= 0.029),
      pathological stage (pT3b or higher vs pT2; OR: 5.14; 95% CI: 1.92-13.78; P =
      0.001) and percentage of the tumor (OR: 46.71; 95% CI: 6.37-342.57; P< 0.001)
      were independent predictive factors for PSMs. The most common location of PSMs in
      patients at high-risk was the PL aspect, which reflects the reported tumor
      aggressiveness. The only significant predictive factors of PSMs were pathological
      outcomes, such as percentage of the tumor in the specimen and pathological stage.

PMID- 25966624
TI  - Exploring the role of mononuclear phagocytes in the epididymis.
AB  - The onslaught of foreign antigens carried by spermatozoa into the epididymis, an
      organ that has not demonstrated immune privilege, a decade or more after the
      establishment of central immune tolerance presents a unique biological challenge.
      Historically, the physical confinement of spermatozoa to the epididymal tubule
      enforced by a tightly interwoven wall of epithelial cells was considered
      sufficient enough to prevent cross talk between gametes and the immune system
      and, ultimately, autoimmune destruction. The discovery of an intricate
      arrangement of mononuclear phagocytes (MPs) comprising dendritic cells and
      macrophages in the murine epididymis suggests that we may have underestimated the
      existence of a sophisticated mucosal immune system in the posttesticular
      environment. This review consolidates our current knowledge of the physiology of
      MPs in the steady state epididymis and speculates on possible interactions
      between auto-antigenic spermatozoa, pathogens and the immune system by drawing on
      what is known about the immune system in the intestinal mucosa. Ultimately,
      further investigation will provide valuable information regarding the origins of
      pathologies arising as a result of autoimmune or inflammatory responses in the
      epididymis, including epididymitis and infertility. 

PMID- 25966625
TI  - Biobanking efforts and new advances in male fertility preservation for rare and
      endangered species.
AB  - Understanding and sustaining biodiversity is a multi-disciplinary science that
      benefits highly from the creation of organized and accessible collections of
      biomaterials (Genome Resource Banks). Large cryo-collections are invaluable tools
      for understanding, cataloging, and protecting the genetic diversity of the
      world's unique animals and plants. Specifically, the systematic collection and
      preservation of semen from rare species has been developed significantly in
      recent decades with some biobanks now being actively used for endangered species
      management and propagation (including the introduction of species such as the
      black-footed ferret and the giant panda). Innovations emerging from the growing
      field of male fertility preservation for humans, livestock species, and
      laboratory animals are also becoming relevant to the protection and the
      propagation of valuable domestic and wild species. These new approaches extend
      beyond the "classical" methods associated with sperm freezing to include
      testicular tissue preservation combined with xenografting or in vitro culture,
      all of which have potential for rescuing vast amounts of unused germplasm. There
      also are other options under development that are predicted to have a high impact
      within the next decade (stem cell technologies, bio-stabilization of sperm cells
      at ambient temperatures, and the use of genomics tools). However, biobanking
      efforts and new fertility preservation strategies have to expand the way beyond
      mammalian species, which will offer knowledge and tools to better manage species
      that serve as valuable biomedical models or require assistance to reverse
      endangerment. 

PMID- 25966626
TI  - A meta-regression evaluating the effectiveness and prognostic factors of oral
      phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction.
AB  - The effectiveness of phosphodiesterase type 5 inhibitors (PDE5-Is) for erectile
      dysfunction (ED) varies considerably among trials, but available studies
      investigating the factors that affect the effectiveness are few and findings are
      not consistent. A systematic search was performed in PubMed, Cochrane Library,
      and EMBASE to identify randomized controlled trials comparing PDE5-Is with
      placebo for the treatment of ED. The methodological quality of included studies
      was assessed by the Cochrane Collaboration's tool for assessing risk of bias. The
      associations between prespecified study-level factors and effectiveness were
      tested by a random effects meta-regression model. This study included 93 trials
      with 26 139 patients. When all PDE5-Is were grouped together, Caucasian ethnicity
      was associated with 15.636% (95% confidence interval [CI]: 0.858% to 32.579%)
      increase in risk ratio (RR) for Global Assessment Questionnaire question-1 (GAQ
      1), and 1.473 (95% CI: 0.406 to 2.338) score increase in mean difference (MD) for
      posttreatment International Index of Erectile Function-Erectile Function domain
      score (IIEF-EF), compared to Asian ethnicity. A one-score increase in baseline
      IIEF-EF was associated with -5.635% (95% CI: -9.120% to -2.017%) reduction in RR
      for GAQ-1, and -0.229 (95% CI: -0.425 to -0.042) score decrease in MD for
      posttreatment IIEF-EF. In conclusion, PDE5-Is are more effective in Caucasians
      than Asians, and in patients with more severe ED. 

PMID- 25966627
TI  - Regulation of Sperm Capacitation and the Acrosome Reaction by PIP 2 and Actin
      Modulation.
AB  - Actin polymerization and development of hyperactivated (HA) motility are two
      processes that take place during sperm capacitation. Actin polymerization occurs
      during capacitation and prior to the acrosome reaction, fast F-actin breakdown
      takes place. The increase in F-actin during capacitation depends upon
      inactivation of the actin severing protein, gelsolin, by its binding to
      phosphatydilinositol-4, 5-bisphosphate (PIP 2 ) and its phosphorylation on
      tyrosine-438 by Src. Activation of gelsolin following its release from PIP 2 is
      known to cause F-actin breakdown and inhibition of sperm motility, which can be
      restored by adding PIP 2 to the cells. Reduction of PIP 2 synthesis inhibits
      actin polymerization and motility, while increasing PIP 2 synthesis enhances
      these activities. Furthermore, sperm demonstrating low motility contained low
      levels of PIP 2 and F-actin. During capacitation there was an increase in PIP 2
      and F-actin levels in the sperm head and a decrease in the tail. In spermatozoa
      with high motility, gelsolin was mainly localized to the sperm head before
      capacitation, whereas in low motility sperm, most of the gelsolin was localized
      to the tail before capacitation and translocated to the head during capacitation.
      We also showed that phosphorylation of gelsolin on tyrosine-438 depends upon its
      binding to PIP 2 . Stimulation of phospholipase C, by Ca 2 + -ionophore or by
      activating the epidermal-growth-factor-receptor, inhibits tyrosine
      phosphorylation of gelsolin and enhances enzyme activity. In conclusion, these
      data indicate that the increase of PIP 2 and/or F-actin in the head during
      capacitation enhances gelsolin translocation to the head. As a result, the
      decrease of gelsolin in the tail allows the maintenance of high levels of F-actin
      in this structure, which is essential for the development of HA motility. 

PMID- 25966628
TI  - Effect of serum testosterone and percent tumor volume on extra-prostatic
      extension and biochemical recurrence after laparoscopic radical prostatectomy.
AB  - Several studies have revealed that the preoperative serum testosterone and
      percent tumor volume (PTV) predict extra-prostatic extension (EPE) and
      biochemical recurrence (BCR) after radical prostatectomy. This study investigated
      the prognostic significance of serum testosterone and PTV in relation to EPE and
      BCR after laparoscopic radical prostatectomy (LRP). We reviewed 520 patients who
      underwent LRP between 2004 and 2012. PTV was determined as the sum of all
      visually estimated tumor foci in every section. BCR was defined as two
      consecutive increases in the postoperative prostate-specific antigen (PSA) >0.2
      ng ml-1 . The threshold for serum total testosterone was 3.0 ng ml-1 .
      Multivariate logistic regression was used to define the effect of variables on
      the risk of EPE and BCR. A low serum testosterone (<3.0 ng ml-1 ) was associated
      with a high serum PSA, Gleason score, positive core percentage of the prostate
      biopsy, PTV, and all pathological variables. On multivariate analysis, similar to
      previous studies, the serum PSA, biopsy positive core percentage, Gleason score,
      and pathological variables predicted EPE and BCR. In addition, low serum
      testosterone (<3.0 ng ml-1 , adjusted OR, 8.52; 95% CI, 5.04-14.4, P= 0.001)
      predicted EPE and PTV (adjusted OR, 1.02; 95% CI, 1.01-1.05, P= 0.046) predicted
      BCR. In addition to previous predictors of EPE and BCR, low serum testosterone
      and PTV are valuable predictors of EPE and BCR after LRP. 

PMID- 25966629
TI  - MicroRNA-200a is up-regulated in aged rats with erectile dysfunction and could
      attenuate endothelial function via SIRT1 inhibition.
AB  - MiR-200a was shown to be upregulated in the corpus cavernosum (CC) of rats with
      aging-related erectile dysfunction (A-ED) in our previous study. Among its target
      genes, SIRT1 was also reported as a protective factor in erectile function by our
      groups previously. Thus, miR-200a might attenuate the erectile function in A-ED
      via SIRT1 inhibition. In the present study, three animal groups were included:
      aged rats with ED (group AE, n = 8), aged rats with normal erectile function
      (group AN, n = 8), and young rats as normal controls (group YN, n = 8). CCs from
      each group were collected for histological and molecular measurements to validate
      the dysregulation of miR-200a and SIRT1. After that, the cavernous endothelial
      cells (CECs) from CC of aged rats with normal erectile function were transfected
      with miR-200a in vitro. Then the expression of SIRT1 and molecules within the
      eNOS/NO/PKG pathway were measured to investigate whether the transfection could
      imitate the attenuated process of erectile function in the aged. As a result, miR
      200a was upregulated while the SIRT1, the levels of eNOS and cGMP were all
      downregulated in the CCs from AE group. After transfection in vitro, the miR-200a
      was upregulated while the SIRT1 and levels of eNOS and cGMP were obviously
      downregulated. Finally, based on the results of our previous study, we further
      verify that up-regulation of miR-200a could participate in the mechanisms of A-ED
      via SIRT1 inhibition, and mainly attenuate endothelial function via influencing
      the eNOS/NO/PKGpathway. 

PMID- 25966630
TI  - Ladakh, India: the land of high passes and genetic heterogeneity reveals a
      confluence of migrations.
AB  - Owing to its geographic location near the longitudinal center of Asia, Ladakh,
      the land of high passes, has witnessed numerous demographic movements during the
      past millenniums of occupation. In an effort to view Ladakh's multicultural
      history from a paternal genetic perspective, we performed a high-resolution Y
      chromosomal survey of Ladakh, within the context of Y haplogroup and haplotype
      distributions of 41 Asian reference populations. The results of this
      investigation highlight the rich ethnic and genetic diversity of Ladkah which
      includes genetic contributions from disparate regions of the continent including,
      West, East, South and Central Asia. The phylogenetic signals from Ladakh are
      consistent with the Indo-Aryans' occupation during the Neolithic age and its
      historic connection with Tibet, as well as the East-West gene flow associated
      with the Silk Road. 

PMID- 25966631
TI  - Phenotypic spectrum of GNAO1 variants: epileptic encephalopathy to involuntary
      movements with severe developmental delay.
AB  - De novo GNAO1 variants have been found in four patients including three patients
      with Ohtahara syndrome and one patient with childhood epilepsy. In addition, two
      patients showed involuntary movements, suggesting that GNAO1 variants can cause
      various neurological phenotypes. Here we report an additional four patients with
      de novo missense GNAO1 variants, one of which was identical to that of the
      previously reported. All the three novel variants were predicted to impair
      Galphao function by structural evaluation. Two patients showed early-onset
      epileptic encephalopathy, presenting with migrating or multifocal partial
      seizures in their clinical course, but the remaining two patients showed no or a
      few seizures. All the four patients showed severe intellectual disability, motor
      developmental delay, and involuntary movements. Progressive cerebral atrophy and
      thin corpus callosum were common features in brain images. Our study demonstrated
      that GNAO1 variants can cause involuntary movements and severe developmental
      delay with/without seizures, including various types of early-onset epileptic
      encephalopathy. 

PMID- 25966632
TI  - Association analysis of copy numbers of FC-gamma receptor genes for rheumatoid
      arthritis and other immune-mediated phenotypes.
AB  - Segmental duplications (SDs) comprise about 5% of the human genome and are
      enriched for immune genes. SD loci often show copy numbers variations (CNV),
      which are difficult to tag with genotyping methods. CNV in the Fcgamma receptor
      region (FCGR) has been suggested to be associated with rheumatic diseases. The
      objective of this study was to delineate association of FCGR-CNV with rheumatoid
      arthritis (RA), coeliac disease and Inflammatory bowel disease incidence. We
      developed a method to accurately quantify CNV in SD loci based on the intensity
      values from the Immunochip platform and applied it to the FCGR locus. We
      determined the method's validity using three independent assays: segregation
      analysis in families, arrayCGH, and whole genome sequencing. Our data showed the
      presence of two separate CNVs in the FCGR locus. The first region encodes FCGR2A,
      FCGR3A and part of FCGR2C gene, the second encodes another part of FCGR2C, FCGR3B
      and FCGR2B. Analysis of CNV status in 4578 individuals with RA and 5457 controls
      indicated association of duplications in the FCGR3B gene in antibody-negative RA
      (P=0.002, OR=1.43). Deletion in FCGR3B was associated with increased risk of
      antibody-positive RA, consistently with previous reports (P=0.023, OR=1.23). A
      clear genotype-phenotype relationship was observed: CNV polymorphisms of the
      FCGR3A gene correlated to CD16A expression (encoded by FCGR3A) on CD8 T-cells. In
      conclusion, our method allows determining the CNV status of the FCGR locus, we
      identified association of CNV in FCGR3B to RA and showed a functional
      relationship between CNV in the FCGR3A gene and CD16A expression. 

PMID- 25966633
TI  - Altered expression of neuropeptides in FoxG1-null heterozygous mutant mice.
AB  - Foxg1 gene encodes for a transcription factor essential for telencephalon
      development in the embryonic mammalian forebrain. Its complete absence is
      embryonic lethal while Foxg1 heterozygous mice are viable but display
      microcephaly, altered hippocampal neurogenesis and behavioral and cognitive
      deficiencies. In order to evaluate the effects of Foxg1 alteration in adult
      brain, we performed expression profiling in total brains from Foxg1+/-
      heterozygous mutants and wild-type littermates. We identified statistically
      significant differences in expression levels for 466 transcripts (P<0.001), 29 of
      which showed a fold change >= 1.5. Among the differentially expressed genes was
      found a group of genes expressed in the basal ganglia and involved in the control
      of movements. A relevant (three to sevenfold changes) and statistically
      significant increase of expression, confirmed by qRT-PCR, was found in two highly
      correlated genes with expression restricted to the hypothalamus: Oxytocin (Oxt)
      and Arginine vasopressin (Avp). These neuropeptides have an important role in
      maternal and social behavior, and their alteration is associated with impaired
      social interaction and autistic behavior. In addition, Neuronatin (Nnat) levels
      appear significantly higher both in Foxg1+/- whole brain and in hippocampal
      neurons after silencing Foxg1, strongly suggesting that it is directly or
      indirectly repressed by Foxg1. During fetal and neonatal brain development, Nnat
      may regulate neuronal excitability, receptor trafficking and calcium-dependent
      signaling and, in the adult brain, it is predominantly expressed in parvalbumin
      positive GABAergic interneurons. Overall, these results implicate the
      overexpression of a group of neuropeptides in the basal ganglia, hypothalamus,
      cortex and hippocampus in the pathogenesis FOXG1 behavioral impairments.

PMID- 25966634
TI  - Improving preimplantation genetic diagnosis for Fragile X syndrome: two new
      powerful single-round multiplex indirect and direct tests.
AB  - Fragile X syndrome (FraX) is caused by the expansion of an unstable CGG repeat
      located in the Fragile X mental retardation 1 gene (FMR1) gene. Preimplantation
      genetic diagnosis (PGD) can be proposed to couples at risk of transmitting the
      disease, that is, when the female carries a premutation or a full mutation. We
      describe two new single-cell, single-round multiplex PCR for indirect and direct
      diagnosis of FraX on biopsied embryos. These tests include five unpublished,
      highly heterozygous simple sequence repeats, and the co-amplification of non
      expanded CGG repeats for the direct test. Heterozygosity of the new markers
      ranged from 69 to 81%. The mean rate of non-informative marker included in the
      tests was low (26% and 23% for the new indirect and direct tests, respectively).
      This strategy allows offering a PGD for FraX to 96% of couples requesting it in
      our centre. A conclusive genotype was obtained in all cells with a rate of cells
      presenting an allele dropout ranging from 17% for the indirect test to 26% for
      the direct test. The new indirect test was applied for eight PGD cycles: 32
      embryos were analysed, 9 were transferred and 3 healthy babies were born. By
      multiplexing these highly informative markers, robustness of the diagnosis is
      improved and the loss of potentially healthy embryos (because they are non
      diagnosed or misdiagnosed) is limited. This may increase the chances of success
      of couples requesting a PGD for FraX, in particular, when premature ovarian
      insufficiency in premutated women leads to a reduced number of embryos available
      for analysis. 

PMID- 25966635
TI  - Genetics of GNE myopathy in the non-Jewish Persian population.
AB  - GNE myopathy is an autosomal recessive adult-onset disorder characterized by
      progressive muscle atrophy and weakness, initially involving the distal muscles,
      while often sparing the quadriceps. It is caused by variants in the GNE gene that
      encodes a key bifunctional enzyme in the sialic acid biosynthetic pathway. We
      investigated the clinical and molecular characteristics of 18 non-Jewish Persian
      patients from 11 unrelated GNE myopathy families. In addition, we reviewed the
      previously reported cases and suggest genotype-phenotype correlations for the
      identified variants. Comprehensive clinical and laboratory evaluations were
      carried out. Sequencing of the GNE gene was performed using genomic DNA from the
      patients. Screening of the identified variants was performed in all relevant
      family members. Molecular analyses identified three causative homozygous GNE
      variants in 11 families: c.2228T>C (p. M743T) in 7, c.830G>A (p.R277Q) in 2, and
      one novel variation (c.804G>A) in 2 families that results in a synonymous codon
      change (p.L268=) and likely creates a novel splice site affecting the protein
      function. This study confirms that c.2228T>C (p.M743T) is the most prevalent
      disease-causing variant in the non-Jewish Persian population, but other GNE
      variants can cause GNE myopathy in this population. The patients with all three
      different variants had similar ages of onset. The youngest patient was an 18-year
      old girl in whom the c.830G>A (p.R277Q) variant was identified, whereas the
      oldest onset age (31 years) was seen in a male patient with c.804G>A (p.L268=).
      The results of this investigation expand our knowledge about the genotype
      phenotype correlations in GNE myopathy and aid in clinical management and
      therapeutic interventions. 

PMID- 25966636
TI  - Do people from the Jewish community prefer ancestry-based or pan-ethnic expanded
      carrier screening?
AB  - Ancestry-based carrier screening in the Ashkenazi Jewish population entails
      screening for specific autosomal recessive founder mutations, which are rarer
      among the general population. As it is now technically feasible to screen for
      many more diseases, the question arises whether this population prefers a limited
      ancestry-based offer or a pan-ethnic expanded carrier screening panel that goes
      beyond the diseases that are frequent in their own population, and is offered
      regardless of ancestry. An online questionnaire was completed by 145 individuals
      from the Dutch Jewish community (>= 18 years) between April and July 2014. In
      total, 64.8% were aware of the existence of ancestry-based carrier screening, and
      respondents were generally positive about screening. About half (53.8%) preferred
      pan-ethnic expanded carrier screening, whereas 42.8% preferred ancestry-based
      screening. Reasons for preferring pan-ethnic screening included 'everyone has a
      right to be tested', 'fear of stigmatization when offering ancestry-based
      panels', and 'difficulties with identifying risk owing to mixed backgrounds'.
      'Preventing high healthcare costs' was the most important reason against pan
      ethnic carrier screening among those in favor of an ancestry-based panel. In
      conclusion, these findings show that people from the Dutch Jewish community have
      a positive attitude regarding carrier screening in their community for a wide
      range of diseases. As costs of expanded carrier screening panels are most likely
      to drop in the near future, it is expected that these panels will receive more
      support in the future.

PMID- 25966637
TI  - Arg(1809) substitution in neurofibromin: further evidence of a genotype-phenotype
      correlation in neurofibromatosis type 1.

PMID- 25966639
TI  - Utilization of surgical procedures and racial disparity in the treatment of
      urinary incontinence after prostatectomy.
AB  - AIMS: To analyze the rates of incontinence procedures after radical
      prostatectomy, and define the variables associated with them. METHODS: We
      conducted an IRB approved retrospective review of patients with prostate cancer
      who underwent radical prostatectomy at a single institute from January 1998 to
      December 2012. Logistic regression and time to event analyses were performed to
      ascertain variables associated with receipt of incontinence procedure after
      prostatectomy. RESULTS: Four thousand four hundred one men underwent radical
      prostatectomy (69.8% open, 30.1% laparoscopic or robotic) of whom 74.3% were
      white Caucasian and 22.1% were African-American. Overall, 165 (3.7%) patients
      underwent a total of 191 procedures for male urethral sling or artificial urinary
      sphincter placement. African-American men received fewer incontinence procedures
      than white Caucasian men (2.1% versus 4.3%, P = 0.001); and with a longer delay
      after prostatectomy than white Caucasian men (28.3 months versus 19.9 months, P =
      0.029). Men who had a laparoscopic or robotic prostatectomy received an
      incontinence procedure earlier than men who had an open prostatectomy (17.6
      months versus 24.4 months, P = 0.0001). On multivariate analysis, age at
      prostatectomy, diagnosis of incontinence, and race were independently associated
      with receiving an incontinence procedure. CONCLUSIONS: The overall rate of
      incontinence surgery after radical prostatectomy is low at 3.7%. African-American
      men receive incontinence procedures at a lower rate and with a longer delay after
      prostatectomy than white Caucasian men. Further studies are needed to define the
      reasons for this racial disparity in urinary incontinence surgery in the prostate
      cancer survivor. Neurourol. Urodynam. 35:733-737, 2016. (c) 2015 Wiley
      Periodicals, Inc.

PMID- 25966638
TI  - A novel phenotype in N-glycosylation disorders: Gillessen-Kaesbach-Nishimura
      skeletal dysplasia due to pathogenic variants in ALG9.
AB  - A rare lethal autosomal recessive syndrome with skeletal dysplasia, polycystic
      kidneys and multiple malformations was first described by Gillessen-Kaesbach et
      al and subsequently by Nishimura et al. The skeletal features uniformly comprise
      a round pelvis, mesomelic shortening of the upper limbs and defective
      ossification of the cervical spine. We studied two unrelated families including
      three affected fetuses with Gillessen-Kaesbach-Nishimura syndrome using whole
      exome and Sanger sequencing, comparative genome hybridization and homozygosity
      mapping. All affected patients were shown to have a novel homozygous splice
      variant NM_024740.2: c.1173+2T>A in the ALG9 gene, encoding alpha-1,2
      mannosyltransferase, involved in the formation of the lipid-linked
      oligosaccharide precursor of N-glycosylation. RNA analysis demonstrated skipping
      of exon 10, leading to shorter RNA. Mass spectrometric analysis showed an
      increase in monoglycosylated transferrin as compared with control tissues,
      confirming that this is a congenital disorder of glycosylation (CDG). Only three
      liveborn children with ALG9-CDG have been previously reported, all with missense
      variants. All three suffered from intellectual disability, muscular hypotonia,
      microcephaly and renal cysts, but none had skeletal dysplasia. Our study shows
      that some pathogenic variants in ALG9 can present as a lethal skeletal dysplasia
      with visceral malformations as the most severe phenotype. The skeletal features
      overlap with that previously reported for ALG3- and ALG12-CDG, suggesting that
      this subset of glycosylation disorders constitutes a new diagnostic group of
      skeletal dysplasias. 

PMID- 25966640
TI  - Mechanism of Platelet Activation and Hypercoagulability by Antithymocyte
      Globulins (ATG).
AB  - T cell depletion with antithymocyte globulins (ATG) can be complicated by
      thrombopenia and hypercoagulability. The underlying mechanism is still unclear.
      We found that binding of ATG to platelets caused platelet aggregation, alpha
      granule release, membrane phosphatidylserine exposure and the rapid release of
      procoagulant platelet microvesicles (MV). Platelet activation and MV release were
      complement-dependent and required membrane insertion of C5b-8 but not stable
      lytic pore formation by C5b-9. ATG also activated platelets via binding to the
      low-affinity Fc gamma receptor FcgammaRII. However, only complement inhibition
      but not blockade of FcgammaRII prevented MV release and subsequent thrombin
      activation in plasma. In 19 hematopoietic stem cell and kidney transplant
      patients, ATG treatment resulted in thrombopenia and increased plasma levels of d
      dimer and thrombin-antithrombin complexes. Flow cytometric analysis of complement
      fragments on platelet MV in patient plasma confirmed dose-dependent complement
      activation by ATG. However, the rapid rise in MV numbers observed in vitro was
      not seen during ATG treatment. In vitro experiments suggested that this was due
      to adherence of C3b-tagged MV to red blood cells via complement receptor CR1.
      These data suggest a clinically relevant link between complement activation and
      thrombin generation and offer a potential mechanism underlying ATG-induced
      hypercoagulability. 

PMID- 25966641
TI  - Poloxamer 188 Attenuates Cerebral Hypoxia/Ischemia Injury in Parallel with
      Preventing Mitochondrial Membrane Permeabilization and Autophagic Activation.
AB  - While the previous studies have shown poloxamer 188 (P188)'s neuroprotection in
      cultured HT22 cells under oxygen-glucose deprivation (OGD) insults, we
      investigated whether P188 is a potential neuroprotective agent in primary
      cortical neurons (PCNs) and in cerebral ischemia in vivo and whether the possible
      underlying mechanisms correlate with regulating mitochondrial membrane
      permeability (MMP) and autophagy. The protective effects of P188 were tested in
      PCNs in vitro exposed to OGD, as well as in cerebral ischemia in vivo. Cell death
      and viability were detected with LDH and MTT assay, and mitochondrial membrane
      potential was assessed using fluorescence microscopy. The apoptosis and autophagy
      of PCNs were investigated by expressions of cyt-c, caspase-3, light chain 3
      (LC3), and Beclin-1. In addition, a mouse middle cerebral artery occlusion (MCAO)
      model was used to produce focal ischemia, and mice were treated with P188 and
      rapamycin after MCAO 10 min. The infarct volume, neurological scores, and
      phosphorylation of mammalian target of rapamycin (mTOR) were evaluated. The in
      vitro results showed that P188 prevented OGD-induced primary cerebrocortical
      neuron death and inhibited loss of mitochondrial membrane potential, the release
      of mitochondrial apoptogenic factor cytochrome c from mitochondria to the
      cytoplasm, and activation of caspase-3. P188 suppressed the activation of
      autophagy by decreasing LC3-II and Beclin-1 levels under OGD accordingly.
      Moreover, the in vivo results showed that P188 and rapamycin remarkably reduced
      the infarct volume and neurological deficits in the MCAO mouse model of cerebral
      ischemia, respectively. Both P188 and rapamycin induced phosphorylation of mTOR
      and reversed the decreased level upon MCAO. These data indicate that P188
      prevents neuronal cell death resulting from ischemic brain injury and that its
      neuroprotective effects are mediated by preventing mitochondrial membrane
      integrity damage and autophagic activation. Given that it has low toxicity, P188
      might become a potential novel therapy for ischemic injury. 

PMID- 25966642
TI  - C-Reactive Protein Induces Tau Hyperphosphorylation via GSK3beta Signaling
      Pathway in SH-SY5Y Cells.
AB  - Amyloid plaques and neurofibrillary tangles are the key pathological features of
      Alzheimer's disease (AD). Studies have shown that C-reactive protein (CRP)
      increases during inflammatory reactions and, therefore, has been associated with
      AD. However, there is no published report relating the impact of CRP to the
      regulation of tau phosphorylation. In the present study, we investigated the
      effects of CRP on the phosphorylation of tau protein in SH-SY5Y cells. Treatment
      of cells with CRP (5, 10, 20 MUg/ml) resulted in neurotoxicity and apoptosis, as
      was observed by MTT assay and Hoechst staining, respectively. Western blot
      analysis showed that CRP, in a time- and concentration-dependent manner, induced
      the phosphorylation of tau at Ser202 and ser396 in SH-SY5Y cells. Phosphorylation
      of Akt (Ser473) and GSK3beta (Ser9) were decreased by CRP treatment, whereas
      phosphorylation of ERK and p38 were not affected. Pharmacological inhibition of
      GSK3beta reversed the effects induced by CRP, viz., cytotoxicity, apoptosis, and
      tau phosphorylation. Herein, we present a novel mechanism of cell death following
      CRP insult, which activates tau hyperphosphorylation by regulating GSK3beta
      activity. CRP could potentially be used as an important pathological factor for
      the therapeutic intervention of AD.

PMID- 25966643
TI  - Assessment of four protocols for rapid bacterial identification from positive
      blood culture pellets by matrix-assisted laser desorption ionization-time of
      flight mass spectrometry (Vitek(r) MS).
AB  - In this study, we developed and compared four protocols to prepare a bacterial
      pellet from 944 positive blood cultures for direct MALDI-TOF mass spectrometry
      Vitek(r) MS analysis. Protocol 4, tested on 200 monomicrobial samples, allowed
      83% of bacterial identification. This easy, fast, cheap and accurate method is
      promising in daily practice, especially to limit broad range antibiotic
      treatment. 

PMID- 25966644
TI  - Transformation of Escherichia coli JM109 using pUC19 by the Yoshida effect.
AB  - Transformation of non-competent Escherichia coli JM109 was accomplished using
      pUC19 as donor plasmid and sepiolite as the acicular material to promote cell
      piercing via application of friction with a polystyrene stick or a magnetic bar
      on the surface of a hydrogel containing agar. An automatic spreading setup was
      built with a conventional stirring plate and compared to manual spreading.
      Several parameters were optimized, namely, the agar content of the hydrogel (2%),
      concentration of cells (OD=1.3 corresponding to 1.4*10(9) bacterial cells/mL),
      concentration of sepiolite (0.01%), manual versus mechanical spreading (automatic
      spreading more consistent) and spreading time (30s). Efficiency values up to
      4.1*10(4) CFU/MUg pUC19 were obtained. The method proved to be suitable for a
      rapid and low cost transformation of non-competent E. coli JM109, where higher
      values of efficiency do not need to be attained.

PMID- 25966645
TI  - Comparison of three DNA extraction methods for recovery of soil protist DNA.
AB  - The use of molecular methods to investigate protist communities in soil is in
      rapid development this decade. Molecular analysis of soil protist communities is
      usually dependant on direct genomic DNA extraction from soil and inefficient or
      differential DNA extraction of protist DNA can lead to bias in downstream
      community analysis. Three commonly used soil DNA extraction methods have been
      tested on soil samples from three European Long-Term Observatories (LTOs) with
      different land-use and three protist cultures belonging to different phylogenetic
      groups in different growth stages. The methods tested were: ISOm-11063 (a version
      of the ISO-11063 method modified to include a FastPrep (r)-24 mechanical lysis
      step), GnS-GII (developed by the GenoSol platform to extract soil DNA in large
      scale soil surveys) and a commercial DNA extraction kit - Power LyzerTM
      PowerSoil(r) DNA Isolation Kit (MoBio). DNA yield and quality were evaluated
      along with DNA suitability for amplification of 18S rDNA fragments by PCR. On
      soil samples, ISOm-11063 yields significantly higher DNA for two of the three
      soil samples, however, MoBio extraction favors DNA quality. This method was also
      more effective to recover copies of 18S rDNA numbers from all soil types. In
      addition and despite the lower yields, higher DNA quality was observed with DNA
      extracted from protist cultures with the MoBio method. Likewise, a bead-beating
      step shows to be a good solution for DNA extraction of soil protists, since the
      recovery of DNA from protist cultures and from the different soil samples with
      the ISOm method proved to be efficient in recovering PCR-amplifiable DNA. This
      study showed that soil DNA extraction methods provide biased results towards the
      cyst stages of protist organism. 

PMID- 25966646
TI  - Mathematical modeling deciphers the benefits of alternatively-designed conserved
      activatory and inhibitory gene circuits.
AB  - Cells employ a variety of mechanisms as a response to external signals to
      maintain cellular homeostasis. In this study, we examine four activatory and four
      inhibitory protein synthesis mechanisms at both population and single cell level
      that can be triggered by a transient external signal. Activation mechanisms
      result from the assumption that cells can employ four different modes to
      temporarily increase the levels of a protein: decreased mRNA degradation,
      increased mRNA synthesis, decreased protein degradation and increased protein
      synthesis. For the inhibition mechanisms it is assumed that a cell can reduce a
      protein's level through four ways: increased mRNA degradation, reduced mRNA
      synthesis, increased protein degradation and reduced protein synthesis.
      Deterministic and stochastic models were developed to analyze the dynamic
      responses of these eight mechanisms to a transient signal. Three different
      response metrics were used to measure different aspects of the response. These
      metrics are (i) mid-protein abundance (mP), (ii) time required for the protein to
      reach the mid-protein level (mT), and (iii) duration of response (D), which is
      defined as the total time for which the protein (P) abundance are above or below
      of mid-protein level. Our simulations show that of the activation mechanisms, the
      signal-dependent increase in mRNA synthesis and protein synthesis are more
      effective and faster, than the signal dependent decrease in mRNA and protein
      degradation. On the other hand, the mechanism involving signal dependent increase
      in protein synthesis is noisier than the signal dependent increase in mRNA
      synthesis in regard to all metrics used. Of the four inhibition mechanisms, the
      signal-dependent increase in the protein degradation is the most effective and
      fastest of the four inhibition mechanisms. It is also noisiest of the four
      inhibition mechanisms before the protein levels reach a steady state around 100
      minutes. 

PMID- 25966647
TI  - Electrospun Type 1 Collagen Matrices Using a Novel Benign Solvent for Cardiac
      Tissue Engineering.
AB  - Electrospinning is a well-established technique that uses a high electric field
      to fabricate ultra fine fibrous scaffolds from both natural and synthetic
      polymers to mimic the cellular microenvironment. Collagen is one of the most
      preferred biopolymers due to its biocompatibility and widespread occurrence in
      nature. Electrospinning of Collagen alone has been reported with fluoroalcohols
      such as Hexafluoroisopropanol (HFIP) and Trifluoroethanol (TFE), which are toxic
      to the environment. In this study we describe the use of a novel benign binary
      solvent to generate nanofibers of Collagen type 1, which is non-toxic and
      economical. Transmission electron microscopy (TEM) analysis revealed the
      characteristic feature of native collagen namely the 67 nm banding pattern,
      confirming that the triple helical structure was maintained. Scanning Electron
      Microscopy (SEM) analysis showed the fiber diameters to be in the 200-800 nm
      range. Biocompatibility of the three dimensional (3D) scaffolds was established
      by MTT assays using skeletal myoblasts and Confocal Microscopic analysis of
      immunofluorescent stained sections for muscle specific markers such as Desmin and
      Actin. Primary neonatal rat ventricular cardiomyocytes seeded onto the scaffolds
      were able to maintain their contractile function for a period of 17 days. Our
      work provides evidence that Collagen 1 can be electrospun without combining with
      other polymers using a novel benign solvent and we are currently exploring the
      potential of this approach for cardiac and skeletal muscle tissue engineering.
      This article is protected by copyright. All rights reserved. 

PMID- 25966648
TI  - Photoswitching in nanoporous, crystalline solids: an experimental and theoretical
      study for azobenzene linkers incorporated in MOFs.
AB  - In this article, we use the popular photoswitchable molecule, azobenzene, to
      demonstrate that the embedding in a nanoporous, crystalline solid enables a
      precise understanding of light-induced, reversible molecular motion. We
      investigate two similar azobenzene-containing, pillared-layer metal-organic
      frameworks (MOFs): Cu2(AzoBPDC)2(BiPy) and Cu2(NDC)2(AzoBiPy). Experimental
      results from UV-vis spectroscopy and molecular uptake experiments as well as
      theoretical results based on density-functional theory (DFT) show that in the
      Cu2(AzoBPDC)2(BiPy) MOF structure, the azobenzene side groups undergo
      photoisomerization when irradiated with UV or visible light. In a very similar
      MOF structure, Cu2(NDC)2(AzoBiPy), the experimental studies show an unexpected
      absence of photoisomerization. The DFT calculations reveal that in both MOFs the
      initial and final states of the photoswitching process (the trans and the cis
      conformation) have similar energies, which strongly suggests that the reason for
      the effective blocking of photoswitching in the AzoBiPy-based MOFs must be
      related to the switching process itself. More detailed calculations show that in
      Cu2(NDC)2(AzoBiPy) a naphthalene linker from the molecular framework blocks the
      photoisomerization trajectory which leads from the trans to the cis conformation.
      For Cu2(AzoBPDC)2(BiPy), as a result of the different geometry, such a steric
      hindrance is absent. 

PMID- 25966649
TI  - [Dirofilaria repens-infection in a dog in central Germany without any history of
      travel].
AB  - A mixed breed dog was presented with dyspnoea and fever. In the purulent thorax
      aspirate, a nematode larva was found during the cytological examination.
      Subsequent diagnostic tests revealed an infection with Dirofilaria repens, which
      was probably acquired autochthonously in central Germany. Moxidectin was
      administered every 4 weeks for 6 months and shown to be effective as indicated by
      subsequent blood examinations. This case report shows that infection with
      Dirofilaria repens is possible in Germany and can be treated successfully.

PMID- 25966651
TI  - A Comparison of Benefit Limits in Mental Health.
AB  - This study provides insight to policy makers and stakeholders on how three types
      of benefits limits on Medicaid-covered mental health services might affect access
      for consumers diagnosed with severe mental illness. The study used a
      retrospective cohort design with data for Medicaid-covered, community-based
      mental health services provided in Ohio during fiscal year 2010. Log-binomial
      regression was used for the analysis. Results indicate that limits compared have
      significant, varying consequences based on Medicaid coverage and diagnoses. When
      constraining Medicaid costs, policy makers should consider how limits will
      disrupt care and include clinicians in discussions prior to implementation.

PMID- 25966652
TI  - Aetiology, Diagnosis and Surgical Treatment of Primary Hyperparathyroidism in
      Children: New Trends.
AB  - Primary hyperparathyroidism (PHPT) in children is a rare disorder with sharp
      contrasts in its presentation and aetiology compared with the disease process in
      adults. This review outlines the current literature, which is limited to about
      200 cases, with reference to the aetiology, clinical features, outcomes of
      investigations, and surgery in children affected by PHPT. Familial conditions
      account for almost half of all cases of PHPT in children, suggesting that routine
      genetic testing would be appropriate. Neonatal severe hyperparathyroidism
      requires urgent medical attention, and performing total parathyroidectomies
      offers cure, though conservative management is successful in selected cases.
      Familial hyperparathyroidism in older children can be caused by conditions such
      as multiple endocrine neoplasia types 1 and 2a, hyperparathyroidism-jaw tumour
      syndrome and familial hyperparathyroidism. The role of surgery for this group is
      discussed. The use of ultrasound and MIBI (99mTc-methoxyisobutylnitrile) scanning
      appears to accurately localise solitary adenomas in sporadic PHPT, thereby
      supporting the role of minimally invasive parathyroidectomy in children. (c) 2015
      S. Karger AG, Basel.

PMID- 25966653
TI  - Determination of 3-mercaptopropionic acid by HPLC: A sensitive method for
      environmental applications.
AB  - The organic sulfur compound 3-mercaptopropionic acid (3-MPA) is an important
      thiol intermediate in organic sulfur metabolism in natural environments. It is
      generated during degradation of sulfur-containing amino acids (e.g. methionine)
      and from demethylation of dimethylsulfoniopropionate (DMSP). This pathway is an
      alternative enzymatic process in the DMSP catabolism that routes sulfur away from
      the climatically-active dimethyl sulfide (DMS). 3-MPA detection and subsequent
      quantification in different matrices is difficult due to its extreme reactivity.
      We therefore developed a sensitive method for determination of 3-MPA based on pre
      column derivatization with monobromobimane and analysis by high-performance
      liquid chromatography (HPLC) with fluorescence detection. This methodology was
      first tested with 3-MPA standards under low (0.005-0.2MUmolL(-1)) and high (1
      25MUmolL(-1)) concentrations. For the optimization of the reaction, CHES and,
      alternatively, Tris-HCl buffers were evaluated in the derivatization step, with
      Tris-HCl showing more effective separation of thiol derivatives and a better 3
      MPA peak shape. The detection limit was 4.3nmolL(-1) with a 10MUL sample
      injection, and mean recoveries of 3-MPA ranged from 97 to 105% in estuarine
      waters with different salinities (0.17 and 35.9ppt). The linearity (r>0.99) and
      repeatability of detector response, with intra- and inter-day precision (% CV) of
      2.68-7.01% and 4.86-12.5%, respectively, confirmed the reliability of the method.
      Previous 3-MPA analytical methods required immediate analysis due to unstable
      derivatives, but in this method we achieved high stability of the derivatized
      samples when stored at 4 degrees C, with only a 3-5% loss after more than one
      year of storage. This method was successfully applied to measure 3-MPA
      concentrations and rates of 3-MPA production in a variety of intertidal estuarine
      sediment slurries. Dissolved 3-MPA concentrations in these sediment slurries
      varied between 2 and 237MUmolL(-1) and, 3-MPA net fluxes ranged in wet sediments
      between -3.6+/-1.7 and 30+/-5MUmolL(-1)g(-1)h(-1). Thus, the application of this
      optimized methodology showed an efficient performance for measuring 3-MPA in
      environmental samples, with a straightforward sample derivatization and a simple
      analysis of stable 3-MPA derivatives. 

PMID- 25966654
TI  - Temporal and Physiologic Measurements of Deglutition in the Upright and Supine
      Position with Videofluoroscopy (VFS) in Healthy Subjects.
AB  - Cross-sectional imaging has long been employed to examine swallowing in both the
      sagittal and axial planes. However, data regarding temporal swallow measures in
      the upright and supine positions are sparse, and none have employed the MBS
      impairment profile (MBSImP). We report temporal swallow measures, physiologic
      variables, and swallow safety of upright and supine swallowing in healthy
      subjects using videofluoroscopy (VFS). Twenty healthy subjects ages 21-40
      underwent VFS study upright and supine. Subjects were viewed in the sagittal
      plane and swallowed 5 mL liquid and pudding barium. Oral transit time, pharyngeal
      delay time, pharyngeal response time, pharyngeal transit time, and total swallow
      duration were measured. Penetration/aspiration scores and 14 MBSImP variables
      were analyzed in both positions. All subjects completed swallows supine, although
      one aspirated on one liquid bolus. Temporal measures of swallowing were similar
      for pudding upright and supine. Pharyngeal phase swallow measures were longer for
      liquids in supine. MBSImP physiologic measures revealed a pharyngeal delay in
      both positions. Although Pen/Asp range was higher supine, more subjects
      penetrated upright. Temporal measures were increased for liquids in supine.
      Although Pen/Asp range was higher in supine, more subjects penetrated upright.
      These results provide support for cross-sectional supine imaging of swallowing
      for pudding, but perhaps not thin liquids for dysphagic patients. Slightly
      thicker liquids might prove reliable in supine without compromising swallow
      safety. Future research should examine swallow physiology in both positions in
      dysphagic and older healthy subjects.

PMID- 25966655
TI  - Rotigotine Transdermal Patch Improves Swallowing in Dysphagic Patients with
      Parkinson's Disease.
AB  - Abnormal swallowing, dysphagia, is a potentially fatal symptom in Parkinson's
      disease (PD) and is characterized by frequent silent aspiration, an unrecognized
      risk of suffocation and aspiration pneumonia. Several studies have reported that
      the injection of apomorphine, a dopamine agonist, alleviated dysphagia in some
      patients with PD. The effects of other antiparkinson medications against
      dysphagia remain controversial. Rotigotine is another dopamine agonist with non
      oral administration, i.e., a transdermal patch. Its noninvasiveness seems to
      render this medicine even more suitable than apomorphine for dysphasic patients.
      However, no direct evidence has been reported. In the present retrospective open
      label study, we for the first time objectively showed that rotigotine improved
      swallowing on videofluoroscopic examination in dysphagic patients with PD. 

PMID- 25966656
TI  - Four-vessel occlusion model using aged male Wistar rats: a reliable model to
      resolve the discrepancy related to age in cerebral ischemia research.
AB  - Animal models of cerebral ischemia have typically been established and performed
      using young animals, even though cerebral ischemia (CI) affects primarily elderly
      patients. This situation represents a discrepancy that complicates the
      translation of novel therapeutic strategies for CI. Models of transient global CI
      using aged animals have demonstrated an apparent neuroprotective effect on CA1
      hippocampal neurons; however, this effect is not completely understood. Our study
      used a model in which young (3-6 months) and aged (18-21 months) male Wistar rats
      were subjected to 15 min of transient global CI using the four-vessel occlusion
      (4 VO) model. We determined that the 4 VO model can be performed on aged rats
      with a slight increase in mortality rate. In aged rats, the morphological damage
      was completely established by the 4th day after reperfusion, displaying no
      difference from their younger counterparts. These results demonstrated the lack
      of a neuroprotective effect of aging on CA1 hippocampal neurons in aged male
      Wistar rats. This study determined and characterized the morphological damage to
      the CA1 area after 15 min of 4 VO in aged male Wistar rats, validating the use of
      this model in CI and aging research. 

PMID- 25966657
TI  - Deficits in spontaneous burrowing behavior in the rat bilateral monosodium
      iodoacetate model of osteoarthritis: an objective measure of pain-related
      behavior and analgesic efficacy.
AB  - OBJECTIVE: To characterize deficits in burrowing behavior - an ethologically
      relevant rodent behavior - in the monosodium iodoacetate (MIA) rat model of
      osteoarthritis (OA), and the sensitivity of these deficits to reversal by
      analgesic drugs of both prototypical and novel mechanisms of action. A second
      objective was to compare the burrowing assay to a spontaneous locomotor activity
      (sLA) assay. METHOD: Male Wistar Han rats (200-220 g) received intrarticular
      (i.a.) injections of MIA or saline for sham animals. A deficit in the amount of
      sand burrowed from steel tubes filled with 2.5 kg of sand was used as a measure
      of pain-related behavior, and sensitivity to reversal of these deficits by
      analgesic drugs was assessed in bilaterally MIA-injected rats. RESULTS: Bilateral
      MIA injections induced a significant impairment of burrowing behavior, which was
      concentration-dependent. The temporal pattern of the deficits was biphasic: a
      large deficit at 3 days post-injection, resolving by day 14 and returning at the
      21 and 28 day time points. At the 3 day time point ibuprofen, celecoxib and an
      anti-nerve growth factor (NGF) monoclonal antibody (mAb) were able to
      significantly reinstate burrowing behavior, whereas the fatty acid amide
      hydrolase (FAAH) inhibitor PF-04457845 and morphine displayed no reversal effect.
      Morphine impaired burrowing behavior at 3 mg/kg in sham animals. Deficits in
      rearing frequency in the locomotor activity assay proved irreversible by
      analgesics. CONCLUSION: Burrowing behavior provides an objective, non-reflexive
      read-out for pain-related behavior in the MIA model that has predictive validity
      in detecting analgesic efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs)
      and an anti-NGF mAb.

PMID- 25966658
TI  - Reliability of neuronal information conveyed by unreliable neuristor-based leaky
      integrate-and-fire neurons: a model study.
AB  - We conducted simulations on the neuronal behavior of neuristor-based leaky
      integrate-and-fire (NLIF) neurons. The phase-plane analysis on the NLIF neuron
      highlights its spiking dynamics--determined by two nullclines conditional on the
      variables on the plane. Particular emphasis was placed on the operational noise
      arising from the variability of the threshold switching behavior in the neuron on
      each switching event. As a consequence, we found that the NLIF neuron exhibits a
      Poisson-like noise in spiking, delimiting the reliability of the information
      conveyed by individual NLIF neurons. To highlight neuronal information coding at
      a higher level, a population of noisy NLIF neurons was analyzed in regard to
      probability of successful information decoding given the Poisson-like noise of
      each neuron. The result demonstrates highly probable success in decoding in spite
      of large variability--due to the variability of the threshold switching behavior-
      of individual neurons.

PMID- 25966659
TI  - Mortality of Testicular Cancer in East and West Germany 20 Years after
      Reunification: A Gap Not Closed Yet.
AB  - BACKGROUND: The decline of testicular cancer mortality in East Germany began in
      the 1980s, about 10 years later than that recorded in West Germany. We aimed at
      providing up-to-date time trends of testicular cancer mortality rates in Germany.
      MATERIAL AND METHODS: Mortality data from East Germany (1971-2010) and West
      Germany (1954-2010) were provided by the Federal Bureau of Statistics. We
      estimated age-specific and age-standardized mortality rates using the World
      Standard Population. RESULTS: Despite the declining trend in the 2000s, the
      mortality rates of testicular cancer remained higher in East than in West
      Germany. These rates were 5.5 and 2.6 per million person-years in 2010,
      respectively. Age-specific mortality trends by period and birth cohort showed
      that the mortality decline was larger among younger (15-44 years) than elderly
      men. CONCLUSION: The mortality of testicular cancer is still higher in East than
      West Germany. Despite very similar densities of hospital beds, urologists and
      oncologist per million male population in both parts of Germany, we hypothesized
      that a paucity of centers of expertise for treating testicular cancers in the
      East could account for this particular pattern.

PMID- 25966660
TI  - OnabotulinumtoxinA intradetrusorial injections improve sexual function in female
      patients affected by multiple sclerosis: preliminary results.
AB  - PURPOSE: To investigate the effects of onabotulinum toxin type A (Onabot/A)
      intravesical injections on urinary and sexual function in a group of patients
      affected by multiple sclerosis (MS). METHODS: We enrolled 31 MS female patients
      with symptoms of overactive bladder and detrusor overactivity. All patients
      underwent urodynamics and were administered 3-day voiding diary, Incontinence
      Quality of Life (I-QoL) questionnaire, Female Sexual Function Index (FSFI)
      questionnaire, Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Depression
      Rating Scale (HAM-D) before and 3 months after Onabot/A intravesical injection.
      RESULTS: Onabot/A injection significantly improved urinary symptoms as shown by
      the 3-day voiding diary, I-QoL questionnaire and the urodynamic variables. In
      addition, it also significantly improved sexual functioning in continent patients
      and psychological status as demonstrated by the increase in FSFI, HAM-A and HAM-D
      scores. CONCLUSIONS: The Onabot/A-induced positive effect on sexual dysfunction
      in our MS patients is likely due to an indirect effect exerted by the overall
      urological clinical improvement on sexual function at both the psychological and
      emotional levels. The positive effect exerted by Onabot/A on the anxiety and
      depression scale also suggests that urinary symptoms have a negative impact on
      the psychological status of the patients.

PMID- 25966661
TI  - Partial nephrectomy for renal tumors in solitary kidneys: postoperative renal
      function dynamics.
AB  - OBJECTIVE: To describe renal functional outcomes after partial nephrectomy (PN)
      for a tumor in a solitary kidney using the estimated glomerular filtration rate
      eGFR (MDRD equation). PATIENTS AND METHODS: A retrospective review of 103 cases
      of PN in a solitary kidney at Memorial Sloan-Kettering Cancer Center from
      December 1989 to July 2010 was conducted. The postoperative eGFR measurements
      were broken into three timeframes: 1-10 days after PN, 10 days-8 weeks after PN,
      and 4-12 months after PN. Several factors were analyzed for their impact on
      postoperative eGFR on univariate and multivariable analyses. To illustrate the
      change in eGFR after surgery over time, a univariate generalized estimating
      equation (GEE) model was constructed. RESULTS: Median preoperative eGFR was 47
      ml/min/1.72 m(2) (IQR 39, 58). Higher preoperative eGFR, younger age at the time
      of PN, less estimated blood loss during PN, increased time between PN and
      previous radical nephrectomy, and decreased arterial clamp (ischemia) time were
      all significantly associated with increased postoperative eGFR in the early
      postoperative period on multivariable analysis. Younger age and higher
      preoperative eGFR were the only variables significantly associated with increased
      postoperative eGFR at all three time points. From the GEE model, postoperative
      eGFR continues to rise after PN until it reaches a plateau approximately 1 month
      after PN without attaining preoperative levels. CONCLUSION: PN for tumors in a
      solitary kidney is feasible and safe. In our model, non-modifiable factors
      predict the long-term postoperative eGFR: Young patients with healthy kidneys
      have superior renal functional results.

PMID- 25966663
TI  - Chelate effects in sulfate binding by amide/urea-based ligands.
AB  - The influence of chelate and mini-chelate effects on sulfate binding was explored
      for six amide-, amide/amine-, urea-, and urea/amine-based ligands. Two of the
      urea-based hosts were selective for SO4(2-) in water-mixed DMSO-d6 systems.
      Results indicated that the mini-chelate effect provided by a single urea group
      with two NH binding sites appears to provide enhanced binding over two amide
      groups. Furthermore, additional urea binding sites incorporated into the host
      framework appeared to overcome to some extent competing hydration effects with
      increasing water content. 

PMID- 25966662
TI  - Comparison of 30-day perioperative outcomes in adults undergoing open versus
      minimally invasive pyeloplasty for ureteropelvic junction obstruction: analysis
      of 593 patients in a prospective national database.
AB  - PURPOSE: The surgical correction of ureteropelvic junction obstruction (UPJO) is
      indicated to prevent progression to chronic renal insufficiency. Minimally
      invasive surgery (MIS) has become increasingly popular as an approach to UPJO
      correction. We compared the perioperative outcomes between minimally invasive
      (MIP) and open pyeloplasty (OP) in the adult population. METHODS: The current
      study was performed using the American College of Surgeons National Surgical
      Quality Improvement Program. Patients were identified using Current Procedural
      Terminology codes for pyeloplasty between 2005 and 2012, and were stratified
      according to either MIS or open approach. Patients with a diagnosis of malignant
      neoplasm of the kidney were excluded. Following exclusions, 593 patients remained
      for analysis. Primary outcomes of interest were overall perioperative
      complications, need for transfusions, re-intervention rate, prolonged operation
      time (pOT), prolonged length of stay (pLOS), readmission and mortality within 30
      days of surgery. Multivariable logistic regression analyses were performed to
      examine the association between preoperative outcomes and surgical approach.
      RESULTS: In this study, 423 (71.3 %) patients underwent MIP and 170 (28.7 %)
      underwent OP. Patients who underwent MIP had a decreased risk of wound [Odds
      ratio (OR) 0.06, p < 0.009] and overall complications (OR 0.21, p < 0.001),
      transfusions (OR 0.04, p = 0.004) and pLOS [pLOS (OR 0.08, p < 0.001)].
      Conversely, MIP was associated with an increased likelihood of pOT (OR 2.26, p =
      0.002). CONCLUSION: Adults with UPJO undergoing MIP have a lower risk of overall
      complications, transfusions and pLOS compared to OP. Further studies are needed
      to determine whether these benefits offset the increase in expenditures, related
      to longer operative time and costs of disposables.

PMID- 25966664
TI  - Long-term health-related quality of life for patients with Hirschsprung's disease
      at 5 years after transanal endorectal pull-through operation.
AB  - PURPOSE: This study aims to evaluate the health-related quality of life (HRQoL)
      for children as well as parents' satisfaction 5-7 years after transanal pull
      through operation of Hirschsprung's disease. METHODS: The PedsQLTM 4.0-Core
      Measurement Model-and the PedsQLTM 3.0 Healthcare Satisfaction Generic Module
      were used to evaluate the quality of life and parents' satisfaction,
      respectively. Parents of 53 children who were operated by transanal pull-through
      operation 5-7 years earlier were included in the study. RESULTS: The HRQoL of
      children was generally good. The mean scores were 87.3, 95.5, 92.3 and 93.2 % for
      physical, emotional, social and school functioning, respectively. Overflow
      incontinence was significantly affecting physical (beta = -.261), emotional (beta
      = -.299), social (beta = -.42) and school functioning (beta = -.534).
      Constipation significantly affected emotional (beta = -.742), social (beta = 
      .108) and school (beta = -.282) functioning. Failure to thrive was significantly
      affecting social (beta = -.215) and school functioning (beta = -.176). Age at
      time of surgery was affecting physical, emotional, social and school functioning
      (beta = -.686, -.627, -.865 and -.907, respectively). Parents were generally
      satisfied from the healthcare service with an overall satisfaction of 90.7 with
      the least satisfaction (79.8) in family inclusion category. CONCLUSIONS:
      Transanal pull-through operation disease showed a good postoperative long-term
      HRQoL. Overflow incontinence and age at time of surgery had a significant
      negative effect on all the aspects of children's HRQoL. Parental satisfaction was
      good and could be improved by more family inclusion.

PMID- 25966665
TI  - Population pharmacokinetics of edoxaban and its main metabolite in a dedicated
      renal impairment study.
AB  - A model characterizing the population pharmacokinetics (PK) of edoxaban and its
      major metabolite, M4, following a single oral dose of 15 mg administered to
      subjects with varying kidney function was developed. Thirty-two subjects
      contributed with edoxaban plasma, edoxaban urine, and M4 plasma concentrations.
      Edoxaban urine concentrations allowed estimation of renal clearance, and high
      contribution of renal to total clearance enabled estimation of absolute oral
      bioavailability. A 2-compartment model with delayed absorption and elimination
      parameterized as renal clearance linearly related to creatinine clearance (CLcr )
      and nonrenal clearance forming M4 described edoxaban PK. The PK of M4 was
      described with a 1-compartment model. For a typical subject (70 kg; CLcr , 100
      mL/min) bioavailability, clearance, and central and peripheral volume of
      distribution for edoxaban was estimated to 72.3%, 21.0 L/h, 95.4 L, and 54.3 L,
      respectively. For both edoxaban and M4, the model predicted systemic exposure to
      increase 57.0%, 35.0%, and 11.6% in a subject having CLcr of 30, 50, and 80
      mL/min, respectively, compared with a subject having a CLcr of 100 mL/min.
      Concentration ratios (M4 over edoxaban) were predicted to vary with time after
      dose, but with minor influence of kidney function and body weight. Results were
      in agreement with previous analyses. 

PMID- 25966667
TI  - Iron-catalyzed aerobic C-H functionalization of pyrrolones.
AB  - The aerobic oxidation of pyrrolones catalyzed by Fe(OTf)3 to form reactive N
      acyliminium ion intermediates that undergo nucleophilic additions with alcohols
      to give the corresponding products in moderate to good yields is described. 

PMID- 25966666
TI  - Mesenchymal Stem Cells Isolated From Human Gliomas Increase Proliferation and
      Maintain Stemness of Glioma Stem Cells Through the IL-6/gp130/STAT3 Pathway.
AB  - Although mesenchymal stem cells (MSCs) have been implicated as stromal components
      of several cancers, their ultimate contribution to tumorigenesis and their
      potential to drive cancer stem cells, particularly in the unique microenvironment
      of human brain tumors, remain largely undefined. Consequently, using established
      criteria, we isolated glioma-associated-human MSCs (GA-hMSCs) from fresh human
      glioma surgical specimens for the first time. We show that these GA-hMSCs are
      nontumorigenic stromal cells that are phenotypically similar to prototypical bone
      marrow-MSCs. Low-passage genomic sequencing analyses comparing GA-hMSCs with
      matched tumor-initiating glioma stem cells (GSCs) suggest that most GA-hMSCs
      (60%) are normal cells recruited to the tumor (group 1 GA-hMSCs), although,
      rarely (10%), GA-hMSCs may differentiate directly from GSCs (group 2 GA-hMSCs) or
      display genetic patterns intermediate between these groups (group 3 GA-hMSCs).
      Importantly, GA-hMSCs increase proliferation and self-renewal of GSCs in vitro
      and enhance GSC tumorigenicity and mesenchymal features in vivo, confirming their
      functional significance within the GSC niche. These effects are mediated by GA
      hMSC-secreted interleukin-6, which activates STAT3 in GSCs. Our results establish
      GA-hMSCs as a potentially new stromal component of gliomas that drives the
      aggressiveness of GSCs, and point to GA-hMSCs as a novel therapeutic target
      within gliomas.

PMID- 25966668
TI  - Attenuation of food allergy symptoms following treatment with human milk
      oligosaccharides in a mouse model.
AB  - BACKGROUND: The prebiotic nature of human milk oligosaccharides (HMOs) and
      increasing evidence of direct immunomodulatory effects of these sugars suggest
      that they may have some therapeutic potential in allergy. Here, we assess the
      effect of two HMOs, 2'-fucosyllactose and 6'-sialyllactose, on symptomatology and
      immune responses in an ovalbumin-sensitized mouse model of food allergy. METHODS:
      The effects of oral treatment with 2'-fucosyllactose and 6'-sialyllactose on
      anaphylactic symptoms induced by oral ovalbumin (OVA) challenge in sensitized
      mice were investigated. Mast cell functions in response to oral HMO treatment
      were also measured in the passive cutaneous anaphylaxis model, and direct effects
      on IgE-mediated degranulation of mast cells were assessed. RESULTS: Daily oral
      treatment with 2'-fucosyllactose or 6'-sialyllactose attenuated food allergy
      symptoms including diarrhea and hypothermia. Treatment with HMOs also suppressed
      antigen-induced increases in mouse mast cell protease-1 in serum and mast cell
      numbers in the intestine. These effects were associated with increases in the
      CD4(+) CD25(+) IL-10(+) cell populations in the Peyer's patches and mesenteric
      lymph nodes, while 6'-sialyllactose also induced increased IL-10 and decreased
      TNF production in antigen-stimulated splenocytes. Both 2'-fucosyllactose and 6'
      sialyllactose reduced the passive cutaneous anaphylaxis response, but only 6'
      sialyllactose directly inhibited mast cell degranulation in vitro, at high
      concentrations. CONCLUSIONS: Our results suggest that 2'-fucosyllactose and 6'
      sialyllactose reduce the symptoms of food allergy through induction of IL-10(+) T
      regulatory cells and indirect stabilization of mast cells. Thus, human milk
      oligosaccharides may have therapeutic potential in allergic disease.

PMID- 25966669
TI  - Steady-state tilt has no effect on cerebrovascular CO2 reactivity in anterior and
      posterior cerebral circulations.
AB  - NEW FINDINGS: What is the central question of this study? We investigated the
      effects of superimposed tilt and hypercapnia-induced cerebral arteriolar
      dilatation on anterior and posterior cerebrovascular CO2 reactivity using
      hyperoxic rebreathing in human participants. What is the main finding and its
      importance? The main findings are threefold: (i) cerebrovascular CO2 reactivity
      in the anterior and posterior cerebrovasculature is unchanged with tilt; (ii)
      cerebral autoregulation is unlikely responsible due to unchanging cerebrovascular
      resistance reactivity between positions; and (iii) cerebral blood flow is not
      pressure passive during tilt as it is with pharmacological or lower body negative
      pressure-induced changes in mean arterial pressure, suggesting that sympathetic
      activation or balanced transmural pressures during head-down tilt regulate
      cerebral blood flow. Cerebral autoregulation is a protective feature of the
      cerebrovasculature that maintains relatively constant cerebral perfusion in the
      face of static and dynamic fluctuations in mean arterial pressure (MAP). However,
      the extent that the cerebrovasculature can autoregulate in the face of
      superimposed steady-state orthostasis-induced changes in MAP (e.g. head-up and
      head-down tilt; HUT and HDT) and CO2 -mediated arteriolar dilatation is unknown.
      We tested the effects of steady-state tilt on cerebrovascular CO2 reactivity in
      the middle and and posterior cerebral artery in the following five body
      positions: 90 deg HUT, 45 deg HUT, supine, 45 deg HDT and 90 deg HDT on a tilt
      table during a modified hyperoxic rebreathing test. Absolute and relative
      cerebrovascular CO2 reactivity [cerebral blood velocity (CBV)/CO2 ],
      cerebrovascular resistance (CVR) reactivity (CVR/CO2 ) and MAP reactivity
      (MAP/CO2 ) were quantified using linear regression. Mean arterial pressure was
      significantly elevated in 90 deg HDT compared with other positions during
      baseline steady-state tilt (P < 0.01). Absolute CBV/CO2 and CVR/CO2 were greater
      in the middle cerebral artery than the posterior cerebral artery (P < 0.01) in
      all body positions, but relative measures were not different (P = 0.143 and P =
      0.360, respectively), nor was there any interaction with tilt position. In
      addition, there was no difference in absolute (P = 0.556) and relative MAP/CO2 (P
      = 0.308) between positions. Our data demonstrate that cerebral blood flow remains
      well regulated during superimposed steady-state orthostatic stress and dynamic
      changes in the partial pressure of end-tidal CO2 during rebreathing. Cerebral
      autoregulation is likely not the mechanism responsible, but rather sympathetic
      nervous system activation or a balanced cerebrovascular transmural pressure with
      HDT maintains resting cerebral blood flow and cerebrovascular CO2 reactivity
      during rebreathing.

PMID- 25966670
TI  - Are floating stools associated with specific functional bowel disorders?
AB  - BACKGROUND: Functional bowel disorders are recognized as being common, but remain
      very difficult to diagnose accurately and to differentiate from one another,
      despite their significant impact on the quality of life of patients.The aim of
      this study was to evaluate whether the clinical sign of 'floating stools' is
      associated with psychological disorders, colonic transit time, or other specific
      bowel disorders as defined by the Rome III diagnostic criteria. MATERIALS AND
      METHODS: A total of 1252 consecutive patients, referred for and found to have
      functional gastrointestinal disorders, filled in a standard clinical
      questionnaire on the basis of the Rome III diagnostic criteria and were asked to
      provide information on the presence of floating stools. Overall, 344 of these
      scored positive for functional bowel disorders and underwent psychometric testing
      and colonic transit time studies. RESULTS: Floating stools were reported by 26%
      of functional bowel disorder patients and 3% of the other functional
      gastrointestinal disorder patients (P<0.001). The basic demographic
      characteristics, psychometric evaluation scores, Bristol stool form scales, and
      total and segmental colonic transit times were not statistically different
      according to the presence or not of floating stools in these patients. Logistic
      regression showed that mixed irritable bowel syndrome was the only functional
      gastrointestinal disorder associated independently with floating stools
      (P=0.003). CONCLUSION: Floating stools are a characteristic of patients with
      mixed irritable bowel syndrome.

PMID- 25966671
TI  - Submucosal tunneling endoscopic resection for upper gastrointestinal submucosal
      tumors originating from the muscularis propria layer.
AB  - OBJECTIVE: To estimate the safety and efficacy of submucosal tunneling endoscopic
      resection (STER) for upper gastrointestinal submucosal tumors (SMTs) originating
      from the muscularis propria layer. METHODS: During October 2011 and May 2014, a
      total of 80 patients with SMTs underwent STER at our hospital. A submucosal
      tunnel was created from 3-5 cm above the tumor. Endoscopic submucosal dissection
      of the SMT was performed, and then the mucosal incision was closed with several
      clips after the tumor was removed. RESULTS: All the 80 patients underwent STER
      successfully, with a mean operation time of 61.2 min. Eighty-three SMTs were
      removed; among these, 67 were located in the esophagus and 16 in the gastric
      cardia, 68 were leiomyoma, and 15 were gastrointestinal stromal tumors, and 13
      had a diameter no less than 35 mm. The mean tumor size was 23.2 mm; en-bloc
      resection was performed in 97.6% (81/83) of the tumors. Complications were noted
      in 8.75% (7/80) of the cases, and all of them resolved without the need for
      additional surgery. No recurrence was noted during a mean follow-up of 10.2
      months. CONCLUSION: STER appears to be a feasible, safe, and effective method for
      upper gastrointestinal SMTs originating from the muscularis propria layer, even
      when the size of the tumor was larger than 35 mm.

PMID- 25966672
TI  - Assessing overall patient satisfaction in inflammatory bowel disease using
      structural equation modeling.
AB  - BACKGROUND/AIMS: Structural equation modeling (SEM) is a very popular data
      analytic technique for the evaluation of customer satisfaction. We aimed to
      measure the overall satisfaction of inflammatory bowel disease (IBD) patients
      with healthcare in Portugal and to define its main determinants using SEM.
      PATIENTS AND METHODS: The study included three steps: (i) specification of a
      patient satisfaction model that included the following dimensions: Image,
      Expectations, Facilities, Admission process, Assistant staff, Nursing staff,
      Medical staff, Treatment, Inpatient care, Outpatient care, Overall quality,
      Overall satisfaction, and Loyalty; (ii) sample survey from 2000 patients, members
      of the Portuguese Association of the IBD; and (iii) estimation of the
      satisfaction model using partial least squares (XLSTAT-PLSPM). RESULTS: We
      received 498 (25%) valid questionnaires from 324 (66%) patients with Crohn's
      disease and 162 (33%) patients with ulcerative colitis. Our model provided a
      substantial explanation for Overall satisfaction (R=0.82). The mean index of
      overall satisfaction was 74.4 (0-100 scale). The main determinants of Overall
      satisfaction were the Image (beta=0.26), Outpatient care (beta=0.23), and Overall
      quality (beta=0.21), whose mean indices were 83, 75, and 81, respectively.
      Facilities and Inpatient care were the variables with a significant impact on
      Overall satisfaction and the worst mean indices. CONCLUSION: SEM is useful for
      the evaluation of IBD patient satisfaction. The Overall satisfaction of IBD
      patients with healthcare in Portugal is good, but to increase it, IBD services
      need to focus on the improvement of Outpatient care, Facilities, and Inpatient
      care. Our model could be a matrix for a global model of IBD patient satisfaction.

PMID- 25966673
TI  - Comparative study of small boron, silicon and germanium clusters: B(m)Si(n) and
      B(m)Ge(n) (m + n = 2-4).
AB  - Chemically speaking, atomic clusters are very rich, allowing their application in
      a broad range of technological areas such as developing functional materials,
      heterogeneous catalysis, and building optical devices. In this work, high level
      computational chemistry methods were used in a systematic manner to improve the
      characterization of small clusters formed by boron, silicon, germanium, mixed
      boron/silicon, and mixed boron/germanium. Calculations were carried out with both
      ab initio [MP2 and CCSD(T)] and density functional (B3LYP) methods with extended
      basis sets. The CCSD(T) results were then extrapolated to the complete basis set
      (CBS) limit. Finally, geometrical parameters, vibrational frequencies, and
      relative energies were then obtained and compared to data presented in the
      literature. Graphical Abstract Small boron, silicon and germanium clusters: BmSin
      and BmGen (m + n = 2-4). 

PMID- 25966674
TI  - Quantum chemical investigation on the role of Li adsorbed on anatase (101)
      surface nano-materials on the storage of molecular hydrogen.
AB  - Lithiation of TiO2 has been shown to enhance the storage of hydrogen up to 5.6
      wt% (Hu et al. J Am Chem Soc 128:11740-11741, 2006). The mechanism for the
      process is still unknown. In this work we have carried out a study on the
      adsorption and diffusion of Li atoms on the surface and migration into subsurface
      layers of anatase (101) by periodic density functional theory calculations
      implementing on-site Coulomb interactions (DFT+U). The model consists of 24
      [TiO2] units with 11.097 * 7.655 A(2) surface area. Adsorption energies have been
      calculated for different Li atoms (1-14) on the surface. A maximum of 13 Li atoms
      can be accommodated on the surface at two bridged O, Ti-O, and Ti atom adsorption
      sites, with 83 kcal mol(-1) adsorption energy for a single Li atom adsorbed
      between two bridged O atoms from where it can migrate into the subsurface layer
      with 27 kcal mol(-1) energy barrier. The predicted adsorption energies for H2 on
      the lithiated TiO2 (101) surface with 1-10 Li atoms revealed that the highest
      adsorption energies occurred on 1-Li, 5-Li, and 9-Li surfaces with 3.5, 4.4, and
      7.6 kcal mol(-1), respectively. The values decrease rapidly with additional H2 co
      adsorbed on the lithiated surfaces; the maximum H2 adsorption on the 9Li-TiO2(a)
      surface was estimated to be only 0.32 wt% under 100 atm H2 pressure at 77 K. The
      result of Bader charge analysis indicated that the reduction of Ti occurred
      depending on the Li atoms covered on the TiO2 surface. 

PMID- 25966675
TI  - Biological responses of preosteoblasts to particulate and ion forms of Co-Cr
      alloy.
AB  - This study compared the particulate and ion forms of a cobalt-chrome (Co-Cr)
      alloy on the differentiation/activation of preosteoblasts. Mouse preosteoblasts
      (MC3T3-E1) were cultured in an osteoblast-induction medium in the presence of
      particulate and ion forms of a Co-Cr alloy, followed by cell proliferation and
      cytotoxicity evaluations. The maturation and function of osteoblasts were
      assessed by alkaline phosphatase (ALP) assay and related gene expressions. Both
      particulate and ion forms of the metals significantly reduced the proliferation
      of MC3T3-E1 cells in a dose-dependent manner. Similarly, cells challenged with
      high concentrations of particles and ions exhibited a marked cytotoxic effect and
      diminished expression of ALP. Real-time (RT) polymerase chain reaction (PCR) data
      have suggested that cells with Co-Cr particles dramatically promoted over
      expression of monocyte chemo-attractant protein-1 (MCP-1), tumor necrosis factor
      alpha (TNF-alpha), and interleukin-6 (IL-6), whereas Co(2+) ions treatment
      predominately up-regulated expressions of receptor activator of nuclear factor
      kappa-B ligand (RANKL), nuclear factor of activated T-cells cytoplasmic 1
      (NFATc1), and down-regulated expression of osteoprotegerin (OPG) and Osterix
      (Osx). Overall, this study provides evidence that both Co-Cr alloy particles and
      metal ions interfered with the MC3T3-E1 cells for their growth, maturation, and
      functions. Further, Co-Cr particles exhibited stronger effects on inflammatory
      mediators, while metal ions showed more influence on inhibition of osteoblast
      differentiation and promotion of osteoclastogenesis.

PMID- 25966676
TI  - "Pruning of biomolecules and natural products (PBNP)": an innovative paradigm in
      drug discovery.
AB  - The source or inspiration of many marketed drugs can be traced back to natural
      product research. However, the chemical structure of natural products covers a
      wide spectrum from very simple to complex. With more complex structures it is
      often desirable to simplify the molecule whilst retaining the desired biological
      activity. This approach seeks to identify the structural unit or pharmacophore
      responsible for the desired activity. Such pharmacophores have been the start
      point for a wide range of lead generation and optimisation programmes using
      techniques such as Biology Oriented Synthesis, Diversity Oriented Synthesis,
      Diverted Total Synthesis, and Fragment Based Drug Discovery. This review
      discusses the literature precedence of simplification strategies in four areas of
      natural product research: proteins, polysaccharides, nucleic acids, and compounds
      isolated from natural product extracts, and their impact on identifying
      therapeutic products. 

PMID- 25966678
TI  - Self- and Co-regulation of Anger and Fear in Preschoolers with Autism Spectrum
      Disorders: The Role of Maternal Parenting Style and Temperament.
AB  - Emotion regulation (ER) difficulties are a major concern in children with autism
      spectrum disorder (ASD). Maternal temperament and parenting style have
      significant effects on children's ER. However, these effects have not been
      studied in children with ASD. Forty preschoolers with ASD and their mothers and
      forty matched controls engaged in fear and anger ER paradigms, micro-coded for
      child self- and co-regulatory behaviors and parent's regulation-facilitation.
      Mothers' parenting style and temperament were self-reported. In the ASD group
      only, maternal authoritarian style predicted higher self-regulation and lower co
      regulation of anger and maternal authoritative style predicted higher self
      regulation of fear. Maternal temperament did not predict child's ER. Findings
      emphasize the importance of maternal flexible parenting style in facilitating ER
      among children with ASD. 

PMID- 25966680
TI  - Can Dynamics Be Responsible for the Complex Multipeak Infrared Spectra of NO
      Adsorbed to Copper(II) Sites in Zeolites?
AB  - Copper-exchanged SSZ-13 is a very efficient material in the selective catalytic
      reduction of NO(x) using ammonia (deNO(x)-SCR) and characterizing the underlying
      distribution of copper sites in the material is of prime importance to understand
      its activity. The IR spectrum of NO adsorbed to divalent copper sites are modeled
      using ab initio molecular dynamics simulations. For most sites, complex multi
      peak spectra induced by the thermal motion of the cation as well as the adsorbate
      are found. A finite temperature spectrum for a specific catalyst was constructed,
      which shows excellent agreement with previously reported data. Additionally these
      findings allow active and inactive species in deNO(x)-SCR to be identified. To
      the best of our knowledge, this is the first time such complex spectra for single
      molecules adsorbed to single active centers have been reported in heterogeneous
      catalysis, and we expect similar effects to be important in a large number of
      systems with mobile active centers.

PMID- 25966679
TI  - Periarticular injections with continuous perfusion of local anaesthetics provide
      better pain relief and better function compared to femoral and sciatic blocks
      after TKA: a randomized clinical trial.
AB  - PURPOSE: Combined femoral and sciatic nerve blocks for post-operative pain
      management following total knee arthroplasty (TKA) improve patient satisfaction,
      decrease narcotic consumption and improve pain. However, accompanying motoric
      weakness can cause falls and related complications. We wonder whether peri
      capsular injections in combination with intra-articular perfusion of local
      anaesthetics would result in equal or less pain without the related complications
      of nerve blocks. The objective of the study was to verify these aspects in a
      prospective randomized trial comparing both treatments. METHODS: Fifty TKA
      patients randomly received either a femoral (continuous) and a sciatic (single
      shot) nerve block (CFNB group, 25 knees) or periarticular infiltrations and a
      continuous post-operative intra-articular infusion (PIAC group, 25 knees). VAS
      for pain, pain medication consumption, functional assessment, straight leg
      raising as well as KSS were recorded post-operatively for 6 days. RESULTS: VAS (p
      < 0.001) and KSS (p = 0.05) were significantly better for PIAC. There was
      increased pain following CFNB compared to PIAC. Catheters stayed for 4 days, a
      pain 'rebound' occurred after removing in CFNB but not after PIAC. There was no
      difference in regard to knee function (n.s.), but straight leg raising was
      significant better following PIAC. There were two falls in patients with CFNB.
      CONCLUSION: Peri-capsular injections combined with an intra-articular catheter
      provide better pain control, no rebound pain with better function and might
      decrease the risk of complications related to motor weakness. LEVEL OF EVIDENCE:
      I.

PMID- 25966677
TI  - Targeted nanoparticles for image-guided treatment of triple-negative breast
      cancer: clinical significance and technological advances.
AB  - Effective treatment of triple-negative breast cancer (TNBC) with its aggressive
      tumor biology, highly heterogeneous tumor cells, and poor prognosis requires an
      integrated therapeutic approach that addresses critical issues in cancer therapy.
      Multifunctional nanoparticles with the abilities of targeted drug delivery and
      noninvasive imaging for monitoring drug delivery and responses to therapy, such
      as theranostic nanoparticles, hold great promise toward the development of novel
      therapeutic approaches for the treatment of TNBC using a single therapeutic
      platform. The biological and pathological characteristics of TNBC provide insight
      into several potential molecular targets for current and future nanoparticle
      based therapeutics. Extensive tumor stroma, highly proliferative cells, and a
      high rate of drug resistance are all barriers that must be appropriately
      addressed in order for these nanotherapeutic platforms to be effective.
      Utilization of the enhanced permeability and retention effect coupled with active
      targeting of cell surface receptors expressed by TNBC cells, and tumor-associated
      endothelial cells, stromal fibroblasts, and macrophages is likely to overcome
      such barriers to facilitate more effective drug delivery. An in-depth summary of
      current studies investigating targeted nanoparticles in preclinical TNBC mouse
      and human xenograft models is presented. This review aims to outline the current
      status of nanotherapeutic options for TNBC patients, identification of promising
      molecular targets, challenges associated with the development of targeted
      nanotherapeutics, the research done by our group as well as by others, and future
      perspectives on the nanomedicine field and ways to translate current preclinical
      studies into the clinic.

PMID- 25966681
TI  - No prognostic value of routine cerebrospinal fluid biomarkers in a population
      based cohort of 407 multiple sclerosis patients.
AB  - BACKGROUND: We aimed to determine the association of clinical and routine
      cerebrospinal fluid biochemical markers (total protein, IgG index and oligoclonal
      bands) with disability in multiple sclerosis and whether these biomarkers
      assessed at diagnosis add prognostic value. METHODS: We followed a cohort of
      patients included in the Multiple Sclerosis Lorraine Register (eastern France)
      who had a diagnosis of multiple sclerosis for at least 5 years, as well as
      biological markers values and MRI findings (Barkhof's criteria). In a Cox
      regression model, endpoint was time to score of 4 on the Expanded Disability
      Status Scale (EDSS) (i.e., limited time walking without aid or rest for more than
      500 m). RESULTS: For 407 patients included, the median time from multiple
      sclerosis onset to EDSS score 4 was 4.5 years [2.2-7.2]. Cerebrospinal fluid
      total protein factor < 500 mg/L was associated with EDSS score 4 on bivariate
      analysis (hazard ratio 0.66, 95% confidence interval 0.46-0.95, p = 0.02). On
      multivariate analysis, older age at disease onset (>=50 years) and initial
      primary progressive course of MS but not biological markers predicted worse
      prognosis. CONCLUSION: Routine cerebrospinal fluid biological markers at
      diagnosis were not prognostic factors of multiple sclerosis progression.

PMID- 25966683
TI  - Lenalidomide reduces microglial activation and behavioral deficits in a
      transgenic model of Parkinson's disease.
AB  - BACKGROUND: Parkinson's disease (PD) is one of the most common causes of dementia
      and motor deficits in the elderly. PD is characterized by the abnormal
      accumulation of the synaptic protein alpha-synuclein (alpha-syn) and degeneration
      of dopaminergic neurons in substantia nigra, which leads to neurodegeneration and
      neuroinflammation. Currently, there are no disease modifying alternatives for PD;
      however, targeting neuroinflammation might be a viable option for reducing motor
      deficits and neurodegeneration. Lenalidomide is a thalidomide derivative designed
      for reduced toxicity and increased immunomodulatory properties. Lenalidomide has
      shown protective effects in an animal model of amyotrophic lateral sclerosis, and
      its mechanism of action involves modulation of cytokine production and inhibition
      of NF-kappaB signaling. METHODS: In order to assess the effect of lenalidomide in
      an animal model of PD, mThy1-alpha-syn transgenic mice were treated with
      lenalidomide or the parent molecule thalidomide at 100 mg/kg for 4 weeks.
      RESULTS: Lenalidomide reduced motor behavioral deficits and ameliorated
      dopaminergic fiber loss in the striatum. This protective action was accompanied
      by a reduction in microgliosis both in striatum and hippocampus. Central
      expression of pro-inflammatory cytokines was diminished in lenalidomide-treated
      transgenic animals, together with reduction in NF-kappaB activation. CONCLUSION:
      These results support the therapeutic potential of lenalidomide for reducing
      maladaptive neuroinflammation in PD and related neuropathologies.

PMID- 25966682
TI  - Tfap2a and 2b act downstream of Ptf1a to promote amacrine cell differentiation
      during retinogenesis.
AB  - Retinogenesis is a precisely controlled developmental process during which
      different types of neurons and glial cells are generated under the influence of
      intrinsic and extrinsic factors. Three transcription factors, Foxn4, RORbeta1 and
      their downstream effector Ptf1a, have been shown to be indispensable intrinsic
      regulators for the differentiation of amacrine and horizontal cells. At present,
      however, it is unclear how Ptf1a specifies these two cell fates from competent
      retinal precursors. Here, through combined bioinformatic, molecular and genetic
      approaches in mouse retinas, we identify the Tfap2a and Tfap2b transcription
      factors as two major downstream effectors of Ptf1a. RNA-seq and immunolabeling
      analyses show that the expression of Tfap2a and 2b transcripts and proteins is
      dramatically downregulated in the Ptf1a null mutant retina. Their overexpression
      is capable of promoting the differentiation of glycinergic and GABAergic amacrine
      cells at the expense of photoreceptors much as misexpressed Ptf1a is, whereas
      their simultaneous knockdown has the opposite effect. Given the demonstrated
      requirement for Tfap2a and 2b in horizontal cell differentiation, our study thus
      defines a Foxn4/RORbeta1-Ptf1a-Tfap2a/2b transcriptional regulatory cascade that
      underlies the competence, specification and differentiation of amacrine and
      horizontal cells during retinal development. 

PMID- 25966685
TI  - Learning fluid prescription skills: why is it so challenging?
AB  - BACKGROUND: It is well recognised that medical students and junior doctors find
      fluid prescription a challenging topic. This study was designed to gain a greater
      understanding of the experiences that medical students face related to learning
      about fluid prescribing. METHODS: A qualitative approach, using focus groups, was
      employed in this research. Final-year medical students in academic year 2011-12
      at Queen's University Belfast were invited to participate during their
      'Assistantship' placement in March 2012. Discussions in focus groups, consisting
      of between six and eight students, were recorded and transcribed verbatim. The
      research team, consisting of three separate investigators, conducted thematic
      analysis independently. A final consensus regarding emerging themes was reached
      by discussion within the whole research team. Medical students and junior doctors
      find fluid prescription a challenging topic RESULTS: Five prominent themes
      emerged: 'Teaching experience: a disruptive variation'; 'Curricular
      disconnections'; 'The driving test: Theory-practice transformation'; 'Role
      modelling: which standard to aspire to?'; and finally 'Reconciling the perceived
      risk'. DISCUSSION: This re search provided insights into medical students'
      opinions of the teaching practices and learning experiences related to fluid
      prescribing. The learning of prescribing skills is complex and contextual. In the
      development of such skills, medical students are often exposed to conflicting
      educational experiences that challenge the novice learner in making judgements on
      best prescribing practice. This study adds to the body of evidence that fluid
      prescription is a difficult topic, and has generated a number of multifaceted and
      strategic recommendations to potentially improve fluid prescription teaching.

PMID- 25966686
TI  - Discovery of Cardiac Calcium Channels.

PMID- 25966684
TI  - Protective effect of Daming capsule against chronic cerebral ischemia.
AB  - BACKGROUND: Accumulating evidence has shown that chronic cerebral ischemia (CCI)
      is one of the major causes of vascular dementia (VD) characterized by
      dysregulated cholesterol homeostasis and lipoprotein disturbances. Positive value
      of lipid-lowering agents has been widely evaluated for the treatment of VD. In
      the present study, we investigated whether Daming capsule (DMC) protected against
      CCI-induced VD and its possible mechanisms of action. DMC is a multi-herbal
      formula composed of Rheum palmatum L., Cassia obtusifolia L., Salvia
      miltiorrhiza, and Panax ginseng C.A., which has been used to treat hyperlipidemia
      for years in China. METHODS: A network pharmacology method was established to
      reveal whether DMC contained any chemical constituent targeting CCI-related
      proteins. Furthermore, the potential anti-CCI effects of DMC (100 mg/kg or 200
      mg/kg) administered for 30 days were investigated in vivo on rats that were
      subjected to permanent bilateral occlusion of the carotid arteries (2-VO).
      Spatial learning and memory abilities were evaluated using a Morris water maze
      (MWM) and morphological changes of cerebral cortex and hippocampus were assessed
      using hematoxylin and eosin staining. Moreover, the lipid peroxidation levels and
      antioxidative capabilities were measured using biochemical analysis. RESULTS: Our
      network pharmacology analysis revealed the existence of multiple CCI-related
      chemical-target interactions in DMC, suggesting a potential protective effect. An
      in vivo experiment verified that 200 mg/kg DMC improved cognitive deficits of 2
      VO rats in the MWM test and attenuated pathological alterations in both the
      cerebral cortex and the hippocampus. Biochemical assays indicated that DMC
      decreased malondialdehyde levels and CCI-elevated superoxide dismutase
      activities, but increased the activities of glutathione peroxidase and catalase.
      CONCLUSIONS: Our findings suggested that DMC protected against cognitive
      dysfunction and nerve injuries caused by CCI, which is most likely related to its
      antioxidant actions.

PMID- 25966687
TI  - The R-Domain: Identification of an N-terminal Region of the alpha2delta-1 Subunit
      Which is Necessary and Sufficient for its Effects on Cav2.2 Calcium Currents.
AB  - Voltage-gated calcium channels (Cav) and their associated proteins are pivotal
      signalling complexes in excitable cell physiology. In nerves and muscle, Cav
      tailor calcium influx to processes including neurotransmission, muscle
      contraction and gene expression. Cav comprise a pore-forming alpha1 and
      modulatory beta and alpha2delta subunits - the latter targeted by anti-epileptic
      and anti-nociceptive gabapentinoid drugs. However, the mechanisms of
      gabapentinoid action are unclear, not least because detailed structure-function
      mapping of the alpha2delta subunit remains lacking. Using molecular biology and
      electrophysiological approaches we have conducted the first systematic mapping of
      alpha2delta subunit structure-function. We generated a series of cDNA constructs
      encoding chimera, from which successive amino acids from the rat alpha2delta-1
      subunit were incorporated into a Type 1 reporter protein - PIN-G, to produce
      sequential extensions from the transmembrane (TM) region towards the N-terminus.
      By successive insertion of a TGA stop codon, a further series of N- to C-terminal
      extension constructs lacking the TM region, were also generated. Using this
      approach we have defined the minimal region of alpha2delta-1 - we term the R
      domain (Rd), that appears to contain all the machinery necessary to support the
      electrophysiological and trafficking effects of alpha2delta-1 on Cav. Structural
      algorithms predict that Rd is conserved across all four alpha2delta subunits,
      including RNA splice variants, and irrespective of phyla and taxa. We suggest,
      therefore, that Rd likely constitutes the major locus for physical interaction
      with the alpha1 subunit and may provide a target for novel Cav therapeutics.

PMID- 25966689
TI  - Emerging Alternative Functions for the Auxiliary Subunits of the Voltage-Gated
      Calcium Channels.
AB  - Voltage gated calcium channels (Cav) are composed of up to five proteins: The ion
      conducting pore subunit alpha1 and the auxiliary subunits alpha2, delta, beta,
      and gamma. Recent reports show that Cavalpha1 and Cavbeta comprise the calcium
      channel core complex and that beta, alpha2 delta and gamma may serve additional
      roles that are independent of the Cavalpha1 subunit. This short review will
      summarize these emerging functions. 

PMID- 25966691
TI  - Inhibition of Voltage-Gated Calcium Channels by RGK Proteins.
AB  - Due to their essential biological roles, voltage-gated calcium channels (VGCCs)
      are regulated by a myriad of molecules and mechanisms. Fifteen years ago, RGK
      proteins were discovered to bind the VGCC beta subunit (Cavbeta) and potently
      inhibit high-voltage activated Ca(2+) channels. RGKs (Rad, Rem, Rem2 and Gem/Kir)
      are a family of monomeric small GTPases belonging to the superfamily of Ras
      GTPases. They exert dual inhibitory effects on VGCCs, decreasing surface
      expression and suppressing surface channels through immobilization of the voltage
      sensor or reduction of channel open probability. While Cavbeta is required for
      all forms of RGK inhibition, not all inhibition is mediated by the RGK-Cavbeta
      interaction. Some RGK proteins also interact directly with the pore-forming
      alpha1 subunit of some types of VGCCs (Cavalpha1). Importantly, RGK proteins
      tonically inhibit VGCCs in native cells, regulating cardiac and neural functions.
      This minireview summarizes the mechanisms, molecular determinants, and
      physiological impact of RGK inhibition of VGCCs. 

PMID- 25966690
TI  - Pharmacology of L-type Calcium Channels: Novel Drugs for Old Targets?
AB  - Inhibition of voltage-gated L-type calcium channels by organic calcium channel
      blockers is a well-established pharmacodynamic concept for the treatment of
      hypertension and cardiac ischemia. Since decades these antihypertensives (such as
      the dihydropyridines amlodipine, felodipine or nifedipine) belong to the most
      widely prescribed drugs world-wide. Their tolerability is excellent because at
      therapeutic doses their pharmacological effects in humans are limited to the
      cardiovascular system. During the last years substantial progress has been made
      to reveal the physiological role of different L-type calcium channel isoforms in
      many other tissues, including the brain, endocrine and sensory cells. Moreover,
      there is accumulating evidence about their involvement in various human diseases,
      such as Parkinson's disease, neuropsychiatric disorders and hyperaldosteronism.
      In this review we discuss the pathogenetic role of L-type calcium channels,
      potential new indications for existing or isoform-selective compounds and
      strategies to minimize potential side effects. 

PMID- 25966688
TI  - Towards a Unified Theory of Calmodulin Regulation (Calmodulation) of Voltage
      Gated Calcium and Sodium Channels.
AB  - Voltage-gated Na and Ca(2+) channels represent two major ion channel families
      that enable myriad biological functions including the generation of action
      potentials and the coupling of electrical and chemical signaling in cells.
      Calmodulin regulation (calmodulation) of these ion channels comprises a vital
      feedback mechanism with distinct physiological implications. Though long-sought,
      a shared understanding of the channel families remained elusive for two decades
      as the functional manifestations and the structural underpinnings of this
      modulation often appeared to diverge. Here, we review recent advancements in the
      understanding of calmodulation of Ca(2+) and Na channels that suggest a
      remarkable similarity in their regulatory scheme. This interrelation between the
      two channel families now paves the way towards a unified mechanistic framework to
      understand vital calmodulin-dependent feedback and offers shared principles to
      approach related channelopathic diseases. An exciting era of synergistic study
      now looms. 

PMID- 25966693
TI  - Voltage-gated Calcium Channels and Autism Spectrum Disorders.
AB  - Autism spectrum disorder is a complex-genetic disease and its etiology is unknown
      for the majority of cases. So far, more than one hundred different susceptibility
      genes were detected. Voltage-gated calcium channels are among the candidates
      linked to autism spectrum disorder by results of genetic studies. Mutations of
      nearly all pore-forming and some auxiliary subunits of voltage gated calcium
      channels have been revealed from investigations of autism spectrum disorder
      patients and populations. Though there are only few electrophysiological
      characterizations of voltage-gated calcium channel mutations found in autistic
      patients these studies suggest their functional relevance. In summary, both
      genetic and functional data suggest a potential role of voltage-gated calcium
      channels in autism spectrum disorder. Future studies require refinement of the
      clinical and systems biological concepts of autism spectrum disorder and an
      appropriate holistic approach at the molecular level, e.g. regarding all facets
      of calcium channel functions.

PMID- 25966692
TI  - Cav1.3 Channels as Key Regulators of Neuron-Like Firings and Catecholamine
      Release in Chromaffin Cells.
AB  - Neuronal and neuroendocrine L-type calcium channels (Cav1.2, Cav1.3) open readily
      at relatively low membrane potentials and allow Ca(2+) to enter the cells near
      resting potentials. In this way, Cav1.2 and Cav1.3 shape the action potential
      waveform, contribute to gene expression, synaptic plasticity, neuronal
      differentiation, hormone secretion and pacemaker activity. In the chromaffin
      cells (CCs) of the adrenal medulla, Cav1.3 is highly expressed and is shown to
      support most of the pacemaking current that sustains action potential (AP)
      firings and part of the catecholamine secretion. Cav1.3 forms Ca(2+)-nanodomains
      with the fast inactivating BK channels and drives the resting SK currents. These
      latter set the inter-spike interval duration between consecutive spikes during
      spontaneous firing and the rate of spike adaptation during sustained
      depolarizations. Cav1.3 plays also a primary role in the switch from "tonic" to
      "burst" firing that occurs in mouse CCs when either the availability of voltage
      gated Na channels (Nav) is reduced or the beta2 subunit featuring the fast
      inactivating BK channels is deleted. Here, we discuss the functional role of
      these "neuron-like" firing modes in CCs and how Cav1.3 contributes to them. The
      open issue is to understand how these novel firing patterns are adapted to
      regulate the quantity of circulating catecholamines during resting condition or
      in response to acute and chronic stress.

PMID- 25966694
TI  - Essential Roles of Intracellular Calcium Release Channels in Muscle, Brain,
      Metabolism, and Aging.
AB  - Calcium (Ca(2+)) release from intracellular stores controls numerous cellular
      processes, including cardiac and skeletal muscle contraction, synaptic
      transmission and metabolism. The ryanodine receptors (RyRs: RyR1, RyR2, RyR3) and
      inositol 1,4,5-trisphosphate receptors (IP3Rs: IP3R1, IP3R2, IP3R3) are the major
      Ca(2+) release channels (CRCs) on the endo/sarcoplasmic reticulum (ER/SR). RyRs
      and IP3Rs comprise macromolecular signaling complexes that include modulatory
      proteins which regulate channel activity in response to extracellular signals
      resulting in intracellular Ca(2+) release. Here we focus on the roles of CRCs in
      heart, skeletal muscle, brain, metabolism, and aging. 

PMID- 25966695
TI  - Voltage-Gated Cav1 Channels in Disorders of Vision and Hearing.
AB  - Cav1 channels mediate L-type Ca(2+) currents that trigger the exocytotic release
      of glutamate from the specialized "ribbon" synapse of retinal photoreceptors
      (PRs) and cochlear inner hair cells (IHCs). Genetic evidence from animal models
      and humans support a role for Cav1.3 and Cav1.4 as the primary Cav channels in
      IHCs and PRs, respectively. Because of the unique features of transmission at
      ribbon synapses, Cav1.3 and Cav1.4 exhibit unusual properties that are well
      suited for their physiological roles. These properties may be intrinsic to the
      channel subunit(s) and/or may be conferred by regulatory interactions with
      synaptic signaling molecules. This review will cover advances in our
      understanding of the function of Cav1 channels at sensory ribbon synapses, and
      how dysregulation of these channels leads to disorders of vision and hearing. 

PMID- 25966696
TI  - Regulation of Postsynaptic Stability by the L-type Calcium Channel CaV1.3 and its
      Interaction with PDZ Proteins.
AB  - Alterations in dendritic spine morphology and postsynaptic structure are a
      hallmark of neurological disorders. Particularly spine pruning of striatal medium
      spiny neurons and aberrant rewiring of corticostriatal synapses have been
      associated with the pathology of Parkinson's disease and LDOPA induced
      dyskinesia, respectively. Owing to its low activation threshold the neuronal L
      type calcium channel CaV1.3 is particularly critical in the control of neuronal
      excitability and thus in the calcium-dependent regulation of neuronal functions.
      CaV1.3 channels are located in dendritic spines and contain a C-terminal class 1
      PDZ domain-binding sequence. Until today the postsynaptic PDZ domain proteins
      shank, densin-180, and erbin have been shown to interact with CaV1.3 channels and
      to modulate their current properties. Interestingly experimental evidence
      suggests an involvement of all three PDZ proteins as well as CaV1.3 itself in
      regulating dendritic and postsynaptic morphology. Here we briefly review the
      importance of CaV1.3 and its proposed interactions with PDZ proteins for the
      stability of dendritic spines. With a special focus on the pathology associated
      with Parkinson's disease, we discuss the hypothesis that CaV1.3 L-type calcium
      channels may be critical modulators of dendritic spine stability. 

PMID- 25966697
TI  - Regulation of Cardiac Calcium Channels in the Fight-or-Flight Response.
AB  - Intracellular calcium transients generated by activation of voltage-gated calcium
      (CaV) channels generate local signals, which initiate physiological processes
      such as secretion, synaptic transmission, and excitation-contraction coupling.
      Regulation of calcium entry through CaV channels is crucial for control of these
      physiological processes. In this article, I review experimental results that have
      emerged over several years showing that cardiac CaV1.2 channels form a local
      signaling complex, in which their proteolytically processed distal C-terminal
      domain, an A-Kinase Anchoring Protein, and cyclic AMP-dependent protein kinase
      (PKA) interact directly with the transmembrane core of the ion channel through
      the proximal C-terminal domain. This signaling complex is the substrate for beta
      adrenergic up-regulation of the CaV1.2 channel in the heart during the fight-or
      flight response. Protein phosphorylation of two sites at the interface between
      the distal and proximal C-terminal domains contributes importantly to control of
      basal CaV1.2 channel activity, and phosphorylation of Ser1700 by PKA at that
      interface up-regulates CaV1.2 activity in response to beta-adrenergic signaling.
      Thus, the intracellular C-terminal domain of CaV1.2 channels serves as a
      signaling platform, mediating beat-to-beat physiological regulation of channel
      activity and up-regulation by beta-adrenergic signaling in the fight-or-flight
      response. 

PMID- 25966699
TI  - Direct Estimation of CaV1.2 Gating Parameters: Quantification of Voltage Sensor -
      Pore Transductions and their Modulation by FLP 64176.
AB  - Calcium agonists such as FPL 64174 increase macroscopic calcium channel currents
      and induce substantial changes in current kinetics. Their molecular mechanism of
      action is currently unknown. Here we propose a technique enabling the estimation
      of FPL 64174 effects on rate constants of the voltage sensing machinery and pore
      transitions from macroscopic CaV1.2 current kinetics making use of a hybrid
      stochastic-deterministic optimization procedure. Current traces of wild type
      CaV1.2, a channel construct with neutralized segment IIS4 (IIS4N) and a pore
      mutant (A780T) were fitted to a circular four-state (rest, activated, open,
      deactivated) channel model in control and FPL 64174 (1 uM). The estimated rate
      constants provided novel insights in how structural elements of the voltage
      sensing unit and the channel pore influence the action of FPL 64174. The new
      approach may be applicable for the analysis of drug effects on other ion channels
      as well as for quantification of VS transitions and rate constants of pore gating
      from macroscopic current kinetics.

PMID- 25966700
TI  - Molecular Aspects of Modulation of L-type Calcium Channels by Protein Kinase C.
AB  - Ca(2+) influx via L-type Ca(2+) channel (L-VDCC; CaV1.2) is required for cardiac
      and smooth muscle contraction. These channels are located in the plasma membrane
      and along the T-tubules (in cardiomyocytes), along with various scaffold and
      trafficking proteins. CaV1.2 is modulated by different hormones and transmitters
      and was implicated in a variety of cardiovascular pathologies, many of which also
      involve protein kinase C (PKC). One of the prominent pathways of PKC activation
      in cardiac and smooth muscle cells is via activation of Gq-coupled receptors and
      subsequent activation of protein lipase C (PLC). CaV1.2 was shown to be
      modulated, phosphorylated by, and associated with PKC both in vitro and in vivo.
      Despite the well documented enhancing effect of vasoconstrictors operating via Gq
      on CaV1.2 channels, the molecular mechanism by which PKC affects the channel has
      not yet been resolved. Furthermore, the nature of PKC modulation of CaV1.2
      appears to be species-, age- and tissue-dependent. Results from experiments in
      heterologous expression systems are often contradicting and are difficult to
      coalesce. The choice of both the heterologous expression system and the CaV1.2
      isoform expressed are at the core of this conundrum. Complete reconstitution of
      the enhancing effect of PKC was successful only in Xenopus oocytes and only when
      the long N-terminus (NT) isoform of the channel was expressed. This review
      summarizes past and new findings regarding the mechanism by which activated PKC
      modulates CaV1.2 channels in native tissues and heterologous expression systems,
      and suggests perspectives for future research. 

PMID- 25966698
TI  - Calcium Channel CaValpha1 Splice Isoforms - Tissue Specificity and Drug Action.
AB  - Voltage-gated calcium ion channels are essential for numerous biological
      functions of excitable cells and there is wide spread appreciation of their
      importance as drug targets in the treatment of many disorders including those of
      cardiovascular and nervous systems. Each Cacna1 gene has the potential to
      generate a number of structurally, functionally, and in some cases
      pharmacologically unique CaValpha1 subunits through alternative pre-mRNA splicing
      and the use of alternate promoters. Analyses of rapidly emerging deep sequencing
      data for a range of human tissue transcriptomes contain information to quantify
      tissue-specific and alternative exon usage patterns for Cacna1 genes.
      Cellspecific actions of nuclear DNA and RNA binding proteins control the use of
      alternate promoters and the selection of alternate exons during pre-mRNA
      splicing, and they determine the spectrum of protein isoforms expressed within
      different types of cells. Amino acid compositions within discrete protein domains
      can differ substantially among CaV isoforms expressed in different tissues, and
      such differences may be greater than those that exist across CaV channel homologs
      of closely related species. Here we highlight examples of CaV isoforms that have
      unique expression patterns and that exhibit different pharmacological
      sensitivities. Knowledge of expression patterns of CaV isoforms in different
      human tissues, cell populations, ages, and disease states should inform
      strategies aimed at developing the next generation of CaV channel inhibitors and
      agonists with improved tissue-specificity. 

PMID- 25966701
TI  - Calcium Channel Subtypes and Exocytosis in Chromaffin Cells at Early Life.
AB  - Here we review the contribution of the various subtypes of voltage-activated
      calcium channels (VACCs) to the regulation of catecholamine release from
      chromaffin cells (CCs) at early life. Patch-clamp recording of inward currents
      through VACCs has revealed the expression of high-threshold VACCs (high-VACCs) of
      the L, N, and PQ subtypes in rat embryo CCs and ovine embryo CCs. Low-threshold
      VACC (low-VACC) currents (T-type) have also been recorded in rat embryo CCs and
      rat neonatal slices of adrenal medullae. Near full blockade by nifedipine and
      nimodipine of the K(+)-elicited secretion as well as the hypoxia induced
      secretion (HIS) supports the dominant role of L-VACC subtypes to the regulation
      of exocytosis at early life. Partial blockade by omega-conotoxin GVIA and omega
      agatoxin IVA suggests a transient participation of N and PQ high-VACCs to the
      regulation of the HIS response at early stages of CC exposure to hypoxia. T-type
      low-VACC current did not elicit exocytosis triggered by electrical depolarising
      pulses applied to rat embryo CCs in one study, but largely contributed to the HIS
      response in neonatal rat adrenal slices in another. In spite of scarce available
      data, the sequence of events driving the HIS response in CCs at early life could
      be established as follows: (i) hypoxia blocks one or more K(+) channels; (ii) as
      a consequence, mild membrane depolarisation occurs; (iii) T-type low-VACCs open
      at membrane potentials more hyperpolarised than those required to recruit the
      high-VACCs; (iv) firing of action potentials then occurs; (v) fast-inactivating N
      and PQ high-VACCs transiently open and low-inactivating L high-VACCs remain open
      along the hypoxia stimulus; (vi) increase of cytosolic Ca(2+) takes place; and
      (vii) the exocytotic release of catecholamine occurs in two phases, an explosive
      initial phase, driven by Ca(2+) entry through L, N and PQ channels, followed by a
      more sustained catecholamine release at a slower rate driven by L-type channels.

PMID- 25966702
TI  - Molecular and functional interplay of voltage-gated Ca2+ channels with the
      cytoskeleton.
AB  - Voltage-gated calcium (CaV) channels conduct Ca(2+) ions into cells in response
      to depolarization and thereby contribute to regulate diverse biological events in
      a wide variety of tissues including nerves, glands and muscles. They are
      responsible for initiation of excitation-contraction and excitation-secretion
      coupling, and are involved in the regulation of protein phosphorylation and gene
      transcription, among many other intracellular events. The activity of CaV
      channels may be regulated by a number of cell surface receptors acting through G
      proteins as well as by protein phosphorylation and other post-translational
      modifications. Likewise, it is acknowledged that CaV channels are organized into
      active signaling platforms depending upon interactions with other molecules
      including cytoskeletal proteins. Diverse studies have shown that several
      cytoskeletal components may act as binding partners that help regulate, localize
      and determine cell surface expression of CaV channel in response to extracellular
      events. In this review, we survey the interaction of CaV channels with the
      cytoskeleton and its potential physiological implications.

PMID- 25966703
TI  - Novel approaches to examine the regulation of voltage-gated calcium channels in
      the heart.
AB  - The cardiac L-type Ca(2+) channel plays a key role in cardiac excitation
      contraction coupling, action potential duration, and gene expression.
      Abnormalities in CaV1.2 function, including increased long-opening-mode gating
      and blunted adrenergic responsiveness, are associated with heart failure and
      hypertrophy. The increased activation of CaV1.2, in turn, triggers Ca(2+) 
      responsive signaling pathways, which contribute to the pathogenesis of heart
      failure and hypertrophy. CaV1.2 in heart is associated with large supramolecular
      complexes that impact on channel trafficking, localization, turnover, and
      function. Much of the prevailing dogma relating to mechanisms underlying CaV1.2
      trafficking and modulation is derived from studies using recombinant channels
      reconstituted in heterologous expression systems. However, recent results using
      knock-in mice indicate that several long-standing "facts" about CaV1.2 regulation
      derived from heterologous expression studies are not replicated in native heart,
      emphasizing the critical need for mechanistic studies in the context of actual
      cardiomyocytes. In this review, we discuss the use of the use of knockin and
      knockout mice as well as new tools, including doxycycline-induced expression of
      informative alpha1C mutants within cardiomyocytes to probe adrenergic regulation
      of CaV1.2. 

PMID- 25966704
TI  - R-Type Voltage-Gated Ca2+ Channels in Cardiac and Neuronal Rhythmogenesis.
AB  - During the past decades, an increasing number of ion channel and transporter
      types have been identified acting together to produce cardiac and neuronal
      pacemaker action potentials. The basis of pacemaker activity was understood in
      more detail by using single-microelectrode recordings on cells isolated from
      pacemaker regions. Meanwhile, this powerful technique was complemented by
      computer modeling and recombinant technologies, including gene inactivation of
      ion channels and transporters, which may be involved in the generation of the
      electrical activity of pacemaker cells. Several genes of the voltage-gated Ca(2+)
      channel (VGCC) family have been ablated, and their role in cardiac and neuronal
      pacemaking is compared in the present summary, focusing on the role of murine R
      type voltage-gated Ca(2+) channels encoded by cacna1e and expressing the ion
      conducting subunit Cav2.3.

PMID- 25966705
TI  - Heterogeneity of Calcium Channel/cAMP-Dependent Transcriptional Activation.
AB  - The major function of the voltage-gated calcium channels is to provide the Ca(2+)
      flux into the cell. L-type voltage-gated calcium channels (Cav1) serve as voltage
      sensors that couple membrane depolarization to many intracellular processes.
      Electrical activity in excitable cells affects gene expression through signaling
      pathways involved in the excitation-transcription (E-T) coupling. E-T coupling
      starts with activation of the Cav1 channel and results in initiation of the cAMP
      response element binding protein (CREB)-dependent transcription. In this review
      we discuss the new quantitative approaches to measuring E-T signaling events. We
      describe the use of wavelet transform to detect heterogeneity of transcriptional
      activation in nuclei. Furthermore, we discuss the properties of discovered
      microdomains of nuclear signaling associated with the E-T coupling and the basis
      of the frequency-dependent transcriptional regulation. 

PMID- 25966706
TI  - CACNB2: An Emerging Pharmacological Target for Hypertension, Heart Failure,
      Arrhythmia and Mental Disorders.
AB  - The voltage-gated Cav1.2 calcium channels respond to membrane depolarization by
      increasing the membrane permeability to Ca(2+), a major signal for cardiac muscle
      contraction, regulation of vascular tone and CREB-dependent transcriptional
      activation. CACNB2 is one of the four homologous genes coding for the auxiliary
      Cavbeta subunits, which are important modulators of the Ca(2+) channel activity.
      Five serious mental disorders - autism spectrum disorder, attention deficit
      hyperactivity disorder, bipolar disorder, major depressive disorder, and
      schizophrenia, - and three major cardiovascular diseases - hypertension, heart
      failure and sudden cardiac death, - have recently been linked to the CACNB2 gene
      coding for the Cavbeta2 subunits. Here I will focus on the Cavbeta2-specific
      molecular determinant beta2-CED as an emerging pharmacological target. 

PMID- 25966707
TI  - Calcium Channel Signaling Complexes with Receptors and Channels.
AB  - Voltage-gated calcium channels are not only mediators of cell signalling events,
      but also are recipients of signalling inputs from G protein coupled receptors
      (GPCRs) and their associated second messenger pathways. The coupling of GPCRs to
      calcium channels is optimized through the formation of receptor-channel
      complexes. In addition, this provides a mechanism for receptorchannel co
      trafficking to and from the plasma membrane. On the other hand, voltage-gated
      calcium channel activity affects other types of ion channels such as voltage-and
      calcium-activated potassium channels. Coupling efficiency between these two
      families of channels is also enhanced through the formation of channel-channel
      complexes. This review provides a concise overview of the current state of
      knowledge on the physical interactions between voltage-gated calcium channels and
      members of the GPCR family, and with other types of ion channels. 

PMID- 25966708
TI  - Editorial: 50th Anniversary of Calcium Channel Research: Biomedical Perspectives.

PMID- 25966709
TI  - Blood microsampling from the ear capillary in non-human primates.
AB  - Blood sampling from awake non-human primates (NHPs) is classically performed
      under constraint in the cephalic or saphenous vein. It is a challenging,
      potentially harmful and stressful procedure which may lead to biased results and
      raises ethical concerns. Laboratory NHPs undergo a head-restrained procedure
      allowing for a safer procedure of collecting blood from their ears. Using regular
      capillary blood collection devices 500 uL of blood can be easily withdrawn per
      puncture point, which is sufficient for performing most of the usual modern
      biological assays. This procedure has been validated by measuring total proteins,
      cortisol and vasopressin concentrations from concomitant blood samples taken from
      the saphenous vein and the ear capillary vessels of macaques (n = 16). We
      observed strong correlations between the blood concentrations of total proteins,
      cortisol and vasopressin (r = 0.72, r = 0.63, r = 0.83, respectively; all P
      values <0.01) taken from the saphenous vein and from the ear capillary. There
      were no significant differences between blood concentrations taken from the
      saphenous vein and the ear capillary. Our alternative to the classical blood
      collection procedure is harmless and can be routinely performed, which can
      therefore improve scientific results while increasing animal welfare in
      accordance with the 3R (replacement, reduction and refinement) principles. 

PMID- 25966711
TI  - A novel unsaturated fatty acid hydratase toward C16 to C22 fatty acids from
      Lactobacillus acidophilus.
AB  - Hydroxy FAs, one of the gut microbial metabolites of PUFAs, have attracted much
      attention because of their various bioactivities. The purpose of this study was
      to identify lactic acid bacteria with the ability to convert linoleic acid (LA)
      to hydroxy FAs. A screening process revealed that a gut bacterium, Lactobacillus
      acidophilus NTV001, converts LA mainly into 13-hydroxy-cis-9-octadecenoic acid
      and resulted in the identification of the hydratase responsible, fatty acid
      hydratase 1 (FA-HY1). Recombinant FA-HY1 was purified, and its enzymatic
      characteristics were investigated. FA-HY1 could convert not only C18 PUFAs but
      also C20 and C22 PUFAs. C18 PUFAs with a cis carbon-carbon double bond at the
      Delta12 position were converted into the corresponding 13-hydroxy FAs.
      Arachidonic acid and DHA were converted into the corresponding 15-hydroxy FA and
      14-hydroxy FA, respectively. To the best of our knowledge, this is the first
      report of a bacterial FA hydratase that can convert C20 and C22 PUFAs into the
      corresponding hydroxy FAs. These novel hydroxy FAs produced by using FA-HY1
      should contribute to elucidating the bioactivities of hydroxy FAs. 

PMID- 25966712
TI  - Health care financing in Nigeria: Implications for achieving universal health
      coverage.
AB  - The way a country finances its health care system is a critical determinant for
      reaching universal health coverage (UHC). This is so because it determines
      whether the health services that are available are affordable to those that need
      them. In Nigeria, the health sector is financed through different sources and
      mechanisms. The difference in the proportionate contribution from these stated
      sources determine the extent to which such health sector will go in achieving
      successful health care financing system. Unfortunately, in Nigeria, achieving the
      correct blend of these sources remains a challenge. This review draws on relevant
      literature to provide an overview and the state of health care financing in
      Nigeria, including policies in place to enhance healthcare financing. We searched
      PubMed, Medline, The Cochrane Library, Popline, Science Direct and WHO Library
      Database with search terms that included, but were not restricted to health care
      financing Nigeria, public health financing, financing health and financing
      policies. Further publications were identified from references cited in relevant
      articles and reports. We reviewed only papers published in English. No date
      restrictions were placed on searches. It notes that health care in Nigeria is
      financed through different sources including but not limited to tax revenue, out
      of-pocket payments (OOPs), donor funding, and health insurance (social and
      community). In the face of achieving UHC, achieving successful health care
      financing system continues to be a challenge in Nigeria and concludes that to
      achieve universal coverage using health financing as the strategy, there is a
      dire need to review the system of financing health and ensure that resources are
      used more efficiently while at the same time removing financial barriers to
      access by shifting focus from OOPs to other hidden resources. There is also need
      to give presidential assent to the national health bill and its prompt
      implementation when signed into law. 

PMID- 25966710
TI  - Receptor-Mediated Mechanism Controlling Tissue Levels of Bioactive Lipid
      Oxidation Products.
AB  - RATIONALE: Oxidative stress is an important contributing factor in several human
      pathologies ranging from atherosclerosis to cancer progression; however, the
      mechanisms underlying tissue protection from oxidation products are poorly
      understood. Oxidation of membrane phospholipids, containing the polyunsaturated
      fatty acid docosahexaenoic acid, results in the accumulation of an end product, 2
      (omega-carboxyethyl)pyrrole (CEP), which was shown to have proangiogenic and
      proinflammatory functions. Although CEP is continuously accumulated during
      chronic processes, such as tumor progression and atherosclerosis, its level
      during wound healing return to normal when the wound is healed, suggesting the
      existence of a specific clearance mechanism. OBJECTIVE: To identify the cellular
      and molecular mechanism for CEP clearance. METHODS AND RESULTS: Here, we show
      that macrophages are able to bind, scavenge, and metabolize carboxyethylpyrrole
      derivatives of proteins but not structurally similar ethylpyrrole derivatives,
      demonstrating the high specificity of the process. F4/80(hi) and M2-skewed
      macrophages are much more efficient at CEP binding and scavenging compared with
      F4/80(lo) and M1-skewed macrophages. Depletion of macrophages leads to increased
      CEP accumulation in vivo. CEP binding and clearance are dependent on 2 receptors
      expressed by macrophages, CD36 and toll-like receptor 2. Although knockout of
      each individual receptor results in diminished CEP clearance, the lack of both
      receptors almost completely abrogates macrophages' ability to scavenge CEP
      derivatives of proteins. CONCLUSIONS: Our study demonstrates the mechanisms of
      recognition, scavenging, and clearance of pathophysiologically active products of
      lipid oxidation in vivo, thereby contributing to tissue protection against
      products of oxidative stress.

PMID- 25966713
TI  - Obstetrics and gynaecology residents' knowledge of the informed consent process
      and its practice in their training institutions.
AB  - INTRODUCTION: The ethical principle of autonomy as expressed in the practice of
      informed consent is a core tenet of clinical practice and good patient physician
      relationship. AIM: The aim was to identify specific gaps in the knowledge of
      trainee obstetricians and gynecologists in Nigeria about the informed consent
      process and its content. It also sought to describe the practice of informed
      consent in their respective institutions. MATERIALS AND METHODS: A survey of
      Residents in obstetrics and gynecology attending the revision course of the
      Faculty of obstetrics and gynecology of the national postgraduate medical college
      was done to determine their knowledge of the informed consent process and its
      practice in their institutions. RESULTS: None of the residents was able to give
      responses that contained all five conditions for informed consent to be valid.
      Furthermore, only 3 (2.22%) Residents mentioned that the name of the surgeon to
      perform the surgery should be part of the information provided to patients during
      the informed consent process. Similarly, only 8 (5.93%) mentioned that
      consequences of not having the surgery should be part of the informed consent
      process. The concept of the 'emancipated minor' being competent to give consent
      was known by 38% of the residents. CONCLUSION: Although Residents in obstetrics
      and gynecology in Nigeria have some knowledge of the informed consent process,
      this knowledge is deficient in key areas such as competence to give consent,
      content and scope of information to be disclosed to patients for surgery. There
      is a need to teach residents the rudiments of informed consent and bioethics in
      general.

PMID- 25966714
TI  - Obstetric outcomes of human herpes virus-2 infection among pregnant women in
      Benin, Nigeria.
AB  - OBJECTIVE: This study investigated the obstetric outcomes of herpes simplex virus
      (HSV-2) infection among pregnant women. MATERIALS AND METHODS: In this
      prospective cohort study, a total of 674 consenting pregnant women attending ante
      natal clinic in the University of Benin Teaching Hospital and Central Hospital
      Benin were recruited between November 2011 and December, 2012. The women were
      screened for HSV-1, and HSV-2 using glycoprotein-G-based type-specific Enzyme
      Linked Immunosorbent Assay on archived blood samples; and were followed up to the
      delivery period and postnatal clinic. The HSV-2-seronegative participants
      underwent second blood sampling for HSV-2 IgG and IgM assay during the delivery
      period. The patients were thus categorized into "HSV-2 seropositive", "HSV-2
      seronegative," and "incident HSV-2 infection" cohorts. The pregnancy outcomes
      were assessed by review of hospital records. Data analysis was with SPSS version
      16 software. RESULTS: Of 674 pregnant women surveyed, 312 (46.3%) were HSV-2
      seropositive; while 362 (56.7%) were HSV-2 seronegative. Comparing the "HSV-2
      seropositive" and "HSV-seronegative" groups, there were no significant
      differences in occurrence of low birth weight (LBW), prematurity, spontaneous
      abortions, and stillbirth events (P=0.96; 0.95; 1.0; and 0.77, respectively).
      Comparing the "incident HSV-2 infection" with the "HSV-2 seronegative" groups,
      the relative risks of occurrence of LBW deliveries, preterm deliveries, and
      stillbirths were 12.6, 25.1, and 4.5, respectively. CONCLUSION: First episode HSV
      2 infection among pregnant women in Benin, Nigeria is associated with an
      increased risk of occurrence of spontaneous abortion, LBW delivery, stillbirths,
      and preterm delivery.

PMID- 25966715
TI  - Pattern of femoral fractures and associated injuries in a Nigerian tertiary
      trauma centre.
AB  - BACKGROUND: The femur is the strongest and largest bone in the human body. It
      therefore requires high-energy trauma for it to fracture unless there is an
      ongoing pathology that weakens the bone. Femoral fractures are thus associated
      with significant pain, deformities, bleeding and varying degrees of injuries. The
      aim of this study is to determine the pattern of femoral fractures and the
      associated injuries in our region while recommending possible means of averting
      these injuries. MATERIALS AND METHODS: A 10-year retrospective study was done in
      National Orthopedic Hospital Enugu from 1994 to 2003. The demographic data,
      etiology, the part of femur affected and associated injuries were collated from
      the hospital records/folders. The analysis was performed using descriptive
      statistics in Microsoft Excel 2007. RESULTS: A total of 562 cases were reviewed,
      63.7% of all the patients were males and the most common etiological factor was
      road traffic accidents. The site of fracture varied with age and etiology with
      26.5% occurring at the mid-shaft with an average age of 27.2 years and 16%
      occurring at the neck of femur, more in the elderly, with 55.6% following minor
      falls and trips. The most common associated injury was soft tissue injuries
      requiring secondary wound closure. CONCLUSION: Femoral fractures are common and
      the pattern varies with age and the mechanism of injury. They are associated with
      other injuries that may be life-threatening.

PMID- 25966716
TI  - Effects of ultrasonic and sonic scaling on surfaces of tooth-colored restorative
      materials: An in vitro study.
AB  - OBJECTIVE: The effects of sonic and ultrasonic scalings (USSs) on the surface
      roughness of nanohybrid, flowable, and polyacid-modified resin composites and
      conventional glass ionomer cement were examined, and the effectiveness of
      repolishing on the scaled material surfaces was determined. MATERIALS AND
      METHODS: The surface roughness of each sample was measured three times before and
      after each scaling and after repolishing, and the data were analyzed using
      repeated measuresanalysis of variance, Tukey's multiple comparisons, and paired t
      tests by a statistical program. RESULTS: Although sonic and USS both
      significantly increased the surface roughness of all the tooth-colored materials,
      USS roughened the surfaces of all the test materials more than SS did. Hence, USS
      may detrimentally affect tooth-colored restorative materials, especially
      conventional glass ionomers and compomers. Repolishing decreased the surface
      roughness of all the materials to near their baseline levels. CONCLUSIONS: On the
      basis of these results, the repolishing of restoration surfaces is strongly
      recommended after dental scalings.

PMID- 25966717
TI  - Assessment of the periapical health of abutment teeth: A retrospective
      radiological study.
AB  - AIM: The aim was to examine the technical quality of root fillings and periapical
      status of root-filled and nonroot-filled teeth restored with crowns and bridge
      retainers through a retrospective analysis of orthopantomographs (OPTGs) in an
      adult Turkish subpopulation. MATERIALS AND METHODS: In this study, the digital
      OPTGs of adult patients between the ages of 20 and 70 who appealed to the
      Endodontics Endodontics Department of the Dentistry Faculty at Marmara University
      (Istanbul, Turkey) for the first time to have their endodontic treatment needs
      met were used. The periapical health of all teeth restored with crowns and bridge
      retainers, and the technical quality of the root fillings on abutment teeth were
      evaluated by radiographic criteria. RESULTS: The survey was carried out using the
      OPTGs of 1000 adult patients composed of 590 (59.0%) women and 410 (41.0%) men.
      4656 (20.9%) of the totally examined 22280 teeth were with crowns and bridge
      retainers. 986 of the total abutment teeth were root-filled and 458 (46.5%) of
      them had apical periodontitis (AP) while 3670 of the total abutment teeth were
      nonroot-filled and 930 (25.3%) of them were with AP. The most commonly treated
      teeth were premolars (33.8%), followed by molars (26.2%), incisors (23.3%) and
      canines (16.7%). Technical quality was proved to be adequate in 27.5% of the root
      fillings. A higher frequency of AP was related to inadequate root fillings
      (P<0.01). CONCLUSION: The frequency of root-filled abutment teeth with AP,
      nonroot-filled abutment teeth with AP, and technically inadequate root-fillings
      among teeth with crowns and bridge retainers was high in the selected adult
      population.

PMID- 25966718
TI  - Use of fetal biometry in the assessment of gestational age in South East Nigeria:
      Femur length and biparietal diameter.
AB  - BACKGROUND: Fetal growth is influenced by many factors such as race,
      socioeconomic status, genetics, geographical location, maternal diseases, and
      number of babies. Consequent upon these, fetal growth charts may vary from one
      location to another even within the same geographical entity. OBJECTIVE: This
      study was designed to establish the fetal growth chart in antenatal women who had
      ultrasound scanning at the University of Nigeria Teaching Hospital, Enugu, South
      East Nigeria. PATIENTS AND METHODS: This is a descriptive analysis of fetal
      biometric measurement of antenatal women. Four hundred and seventy pregnant women
      were studied. RESULTS: The nomogram for the femur length (FL) and biparietal
      diameter (BPD) for the different weeks of gestation (from 13th to the 40th week)
      were established. Correlation coefficients between gestational age and the
      various fetal parameters were also reported. Growth charts using both FL and BPD
      were plotted. A regression model for prediction of fetal age using the fetal
      biometry was also deduced for the studied population. CONCLUSION: The fetal
      parameters used in this study were consistently smaller than reported values from
      European studies up to the 34th week of gestation after which a catch-up growth
      till the 40 weeks was observed. Fetal parameters observed in this study were
      larger than most of the reported Asian values.

PMID- 25966719
TI  - Bladder perforations in children.
AB  - CONTEXT: Bladder perforations in children occur due to several different reasons.
      AIM: In this clinical series study, we focused on bladder perforations due to the
      pelvic injury, and our aim also was to create awareness for a rare type of
      bladder injuries. SETTING AND DESIGN: This was a retrospective study of the
      patients who were treated in our clinic for bladder perforation between 2006 and
      2011. SUBJECTS AND METHODS: We reviewed the documents of childhood bladder
      perforations, and demographic and clinical characteristics of the patients were
      obtained. No statistical analyses were used because of the limited number of
      cases. RESULTS: There were ten patients who suffered from bladder perforation in
      5-year period; 5 were male, and 5 were female. The mean age of the patients was
      4.35 years. Four patients (40%) experienced iatrogenic perforation and six
      patients (60%) experienced perforation due to the accident. Common symptoms were
      hematuria, abdominal tenderness, and inability to urinate. Three patients were
      diagnosed via emergency laparotomy, without any radiological examinations
      performed before surgery. Four patients suffered from the intraperitoneal
      perforation, three patients suffered from extraperitoneal injury and three of
      them both of intraperitoneal and extraperitoneal injuries. Mean recovery time for
      patients was 15 days. One patient developed a urinary tract infection and one
      newborn died due to accompanying morbidities. Nine patients were discharged from
      the hospital. CONCLUSION: If the patients had a pelvic injury, surgeons must pay
      attention for the bladder perforation. Isolated bladder perforations are rare,
      and they are generally associated with iatrogenic injuries. Clinicians should pay
      attention to findings such as anuria, inability to insert a urinary catheter, and
      free fluid in the abdomen in order to diagnose the bladder perforation in
      newborns. Novice surgeons should pay more attention to avoid causing iatrogenic
      bladder perforation during inguinal hernia repair.

PMID- 25966720
TI  - Maternal views and experiences regarding repeat Caesarean section.
AB  - OBJECTIVE: The aim was to determine maternal views and experiences regarding
      repeat caesarean section. METHODS: A pretested and validated semi-structured
      questionnaire was administered to women with prior cesarean section by trained
      research assistants and resident doctors; anonymity and confidentiality were
      strictly observed. The questionnaire comprised information reflecting patients'
      sociodemographic structure, level of education, number of previous cesarean
      section, maternal complications following previous cesarean and opinions about
      acceptance and refusal of cesarean section. RESULTS: Two hundred and twenty-seven
      women participated in the study out of which 157 (69.2%) would accept a repeat
      cesarean section and 70 (30.8%) would not accept. Significant proportion of
      respondents above 35 years of age would refuse a repeat cesarean section (58.6%).
      Religious belief (39.7%) and pain (26.5%) were the most common reasons for
      refusal of cesarean section. CONCLUSION: Appreciable proportion of women with
      previous caesarean section will decline a repeat cesarean section. Re
      orientation, reappraisal and appropriate corrective action in the areas of
      religious belief and postoperative pain management will positively influence our
      women's acceptance of a repeat cesarean section.

PMID- 25966721
TI  - The prevalence of early childhood caries and its associated risk factors among
      preschool children referred to a tertiary care institution.
AB  - OBJECTIVE: The aim was to determine the prevalence of early childhood caries
      (ECC) and its association with infant feeding and oral health-related behavior
      among preschool children aged 6-71 months in Lagos. MATERIALS AND METHODS: This
      was a descriptive cross-sectional study in which 302 children aged 6-71 months
      were selected from four pediatric outpatient clinics in Lagos, Nigeria. A
      structured questionnaire was used to obtain information regarding oral hygiene
      practices, dietary habits, breast and bottle feeding, birth weight of child and
      socioeconomic status of the family, from mothers of the children. The status of
      dental caries was recorded according to the World Health Organization criteria.
      RESULTS: The prevalence of ECC among 302 children aged 6-71 months was 21.2%
      while the mean deft was 0.735. Multivariate logistic regression analysis showed
      the correlation of ECC with the associated risk factors. ECC was significantly
      higher in children who were bottle-fed at night. Method of tooth cleaning other
      than using fluoridated toothpaste significantly increased the prevalence of ECC.
      Breastfeeding for duration of 3-6 months showed significantly lesser caries
      prevalence. Caries significantly increased with age. CONCLUSION: Early childhood
      caries is a multifactorial disease in which prolonged duration of breastfeeding,
      nocturnal bottle feeding, and use of cleaning methods other than fluoridated
      toothpaste are risk factors for ECC. Oral health promotion programs should be
      targeted at mothers, pediatricians, nurses, caretakers at day care centers and
      primary care health workers.

PMID- 25966722
TI  - Effects of edentulism in obstructive sleep apnea syndrome.
AB  - OBJECTIVES: The purpose of this study was to investigate the effects of
      edentulism in obstructive sleep apnea syndrome (OSAS) patients. MATERIALS AND
      METHODS: The study patients' were selected from the Gaziantep University Sleep
      Clinic and Orthodontic Department archives between the years of 2009 and 2011.
      Study groups were determined according to age and edentulism, and the overall
      study population consisted of 42 (21 male, 21 female) OSAS patients. Data from 14
      edentulous (Group I), 14 older dentate (Group II), and 14 middle-aged dentate
      OSAS patients (Group III) were compared in this study. Polysomnographic
      parameters, which were measured and analyzed included: Sleep time, sleep
      efficiency, sleep stage 1, sleep stage 2, sleep stage 3, percentage of rapid eye
      movement sleep, apnea-hypopnea index, oxygen saturation and arousal index. The
      Kruskal-Wallis and Mann-Whitney U statistical tests were used for comparing the
      differences between the three groups and subgroups. RESULTS: Sleep time
      parameters showed significant differences between the groups (P<0.05).
      Differences occurred between Group I and Group III in the sleep time parameter
      (P<0.05), while the edentulous subjects showed lower mean sleep time values when
      compared to the older and middle-aged dentate groups. CONCLUSION: According to
      our results, edentulism may not impact polysomnography parameters, with the
      exception of the sleep time parameter. Important attention should be given to
      edentulous individuals during sleep with their dentures to prevent OSAS
      complications. The use of dentures may prevent or protect patients from the
      predisposing factors of OSAS.

PMID- 25966723
TI  - Effects of azithromycin versus metronidazole-amoxicillin combination as an
      adjunct to nonsurgical periodontal therapy of generalized aggressive
      periodontitis.
AB  - OBJECTIVE: This study evaluated the short-term clinical benefits of two systemic
      antibiotic regimes added to the nonsurgical periodontal treatment of generalized
      aggressive periodontitis. MATERIALS AND METHODS: The patient records were
      reviewed and 45 patients were selected and divided into the following three
      groups: Scaling and root planning (SRP) only; SRP plus azithromycin (AZT group);
      and SRP plus metronidazole and amoxicillin (M+A group). The periodontal indexes
      were recorded at baseline and 3-month posttherapy. RESULTS: The periodontal
      parameters were improved in all groups 3-month posttherapy. The scores were
      decreased more in the AZT and M+A groups than the controls, but this difference
      did not reach significance. In addition, the decrease in the plaque index from
      baseline to 3-month in the AZT group was not significant. CONCLUSION: Nonsurgical
      therapy reduces the probing depth, clinical attachment level, and clinical
      inflammation findings. This healing tendency was observed in the AZT group
      despite the baseline plaque scores. Therefore, AZT might be active against the
      bacteria in dental biofilms.

PMID- 25966724
TI  - Assessment of hygiene habits and attitudes among removable partial denture
      wearers in a university hospital.
AB  - AIMS: The aim of this study was conducting a survey of hygiene habits and use of
      removable partial dentures (RPDs) and correlate them with the social conditions
      of the interviewees. METHODS: A total of 145 RPD wearers were interviewed by
      experienced clinical staff using a structured questionnaire. A Chi-squared test
      was performed to evaluate statistical significance between the variables, and the
      level of significance was P<0.05. RESULTS: A total of 72 (49%) patients reported
      that they had not been well informed by the dentists. Brushing was the most
      frequent cleaning method (57.6%). 77 (53.1%) patients did not take off their
      dentures at night. The frequency of cleaning dentures and using cleansing tablet
      was significantly higher in females than in males (P<0.05). The frequency of
      denture cleaning, cleaned parts of denture, use of cleansing tablet, removal of
      dentures at night, frequency of tooth brushing, does not show any significant
      difference according to age, educational status or duration of denture usage
      (P>0.05). RPD wearers did not clean their dentures and natural teeth
      satisfactorily and had limited knowledge of denture cleansing and oral hygiene
      maintenance. CONCLUSIONS: Hygiene habits and attitudes may be affected by gender,
      but education level and hygiene attitudes may not always present positive
      correlation. Dentists should thoroughly inform patients about the harmful effects
      of overnight wearing and motivate to clean metal parts of RPD's and cleansing
      tablet use in order to minimize the abrasive effect of widely preferred cleaning
      method of brushing with toothpaste.

PMID- 25966725
TI  - Co-infections of hepatitis B and C with human immunodeficiency virus among adult
      patients attending human immunodeficiency virus outpatients clinic in Benin City,
      Nigeria.
AB  - BACKGROUND: Hepatitis B and C viral co-infections with human immunodeficiency
      virus (HIV) are known to affect progression, management, and outcome of HIV
      infection. This study was aimed to access the prevalence of hepatitis B and C co
      infections in HIV-infected adult patients in the University of Benin Teaching
      Hospital with a view of understanding the gravity of this problem in the local
      population. METHODS: The descriptive cross-sectional study was carried out on 342
      HIV-infected adult patients on highly active antiretroviral therapy attending HIV
      Outpatients Clinic of University of Benin Teaching Hospital, between April and
      September, 2011. Patients' sera were screened for hepatitis B surface antigen
      (HBsAg) and anti-hepatitis C virus (HCV) using immunochromatographic-based kits.
      Clinical stage of HIV and CD4+ cell counts were equally evaluated. Data were
      analyzed using SPSS version 17. RESULTS: Of the 324 HIV-infected patients
      screened, 53 (15.5%) were positive for HBsAg, 24 (7.0%) positive for hepatitis C
      virus antibodies (HCV-Ab), while 2 (0.6%) were positive for both viruses.
      Seroprevalence of HBsAg was higher in male (17.8%) than in female (14.7%)
      (chi2=0.49, P=0.49), while the reverse is the case for HCV-Ab; 7.1% for female
      and 6.7% for male (chi2=0.02, P=0.88). Seroprevalences of HBsAg and HCV-Ab were
      also higher among patients in World Health Organization disease stages 3-4 and
      patients with CD4+ cell count<=200 cell/ml compared to those in stages 1-2 and
      with CD4+ cell count>200 cell/ml. CONCLUSION: Co-infection with hepatitis B virus
      and HCV among HIV/acquired immune deficiency syndrome (AIDS) patients is still a
      problem in our environment. Screening for these viruses among HIV/AIDS patients
      will allow for early detection and proper management.

PMID- 25966726
TI  - Red cell alloimmunization in multi-transfused patients with sickle cell anemia in
      Benin City, Nigeria.
AB  - BACKGROUND: Sickle cell anemia (SCA) is an inherited hemoglobin disorder
      characterized by chronic anemia and occasional crises. Clinical features are
      variable. While some individuals are relatively stable and rarely require blood
      transfusion, others often require blood transfusion. Multiple blood transfusion
      is associated with complications including alloimmunization, infections, and iron
      overload. AIMS AND OBJECTIVES: The study aimed at determining the prevalence of
      red cell alloimmunization among multi-transfused patients with SCA. MATERIALS AND
      METHODS: A cross-sectional study of adult SCA patients who have received multiple
      blood transfusion and those who have never received blood was done. Antibody
      screening and identification were carried out using gel technology with
      commercially made panel of cells. RESULTS: A total of 145 SCA subjects were
      studied. They were made up of 86 test group (those that had received two or more
      units of blood) and 59 control group (those that had never received blood
      transfusion). Prevalence of red cell alloantibody among multi-transfused patients
      with SCA was found to be 9.3%. Alloantibodies identified were mainly against
      Rhesus antigens contributing 87.5% (anti-E 37.5%, anti-C 25%, anti-D 12.5%, anti
      e 12.5%). A combination of Kell and Lutheran blood group antigens contributed
      12.5%. No antibody was detected among the control group. CONCLUSION: Blood
      transfusion is associated with the development of alloantibodies. Routine blood
      grouping for multi-transfused patients with SCA should be extended to include
      other blood group antigens in addition to Rhesus D and ABO antigens.

PMID- 25966727
TI  - Epidemiology of active epilepsy in a suburban community in Southeast Nigeria: A
      door-to-door survey.
AB  - CONTEXT: Epilepsy is one of the most common neurologic conditions afflicting an
      estimated 65 million people the world over. Current community-based data on the
      prevalence of active epilepsy in Africa are sparse. AIMS: This study was aimed at
      determining the prevalence and profile of active epilepsy in a suburban community
      in Southeast Nigeria. METHODS: It was a two phase cross-sectional descriptive
      study. In the first phase, those with possible active epilepsy were identified in
      a door-to-door survey using a modification of the World Health Organization
      Neuroscience research protocol. In the second phase, cases of active epilepsy
      were identified and the clinical forms of epilepsy diagnosed based on the
      International League against Epilepsy guidelines 1993. RESULTS: A total of 6,800
      persons was screened in the first phase of the study. There were 29 cases (16
      males and 13 females) of active epilepsy. The point prevalence of active epilepsy
      was 4.3/1,000 (95% confidence interval (95% CI): 2.7-5.9) for the total
      population, 4.9/1,000 (95% CI: 2.5-7.3) for males and 3.7/1,000 (95% CI: 1.7-5.7)
      for females. The age-adjusted prevalence for the total population was 4.1/1,000
      (US Population 2000). Classified using clinical criteria only, generalized
      seizures occurred in 62.1% (n=18) while partial seizures occurred in 37.9% (n=11)
      of cases. CONCLUSIONS: The prevalence of active epilepsy in Southeast Nigeria is
      comparable to that found in developed and some developing countries but less than
      that reported in suburban Southwest Nigeria about three decades ago.

PMID- 25966728
TI  - Knowledge of conversion disorder in children by pediatricians in a developing
      country.
AB  - INTRODUCTION: Conversion disorder (CD) in children presents the clinician with a
      diagnostic and treatment dilemma. Mistaking a physical condition for CD carries
      serious consequences for the child while continued investigation in line with
      physical disease in a child with CD also may expose the child to serious harm.
      MATERIALS AND METHODS: One hundred and seventy-four consenting doctors who
      attended a national conference of pediatricians were administered a 10 item
      questionnaire developed by the researchers. RESULTS: Only 5 (2.9%) of
      participants had good knowledge (scored above the mean plus one standard
      deviation of the score obtained by the psychiatry residents. Gender, rank, years
      of experience, availability of psychiatric service in center and duration of the
      psychiatry posting as the medical student could not differentiate those with
      good/fair knowledge from those without. However, those who have referred children
      for psychiatric assessment (P=0.015), those who believe that children can have CD
      (P=0.000) and those who are fairly confident that they could diagnose CD in
      children (P=0.000) had better knowledge of CD. CONCLUSION: Pediatricians have
      poor knowledge of CDs in children. Those that know that children could have the
      condition have confidence that they can identify children with the condition and
      have referred with mental health problems to psychiatrists have better knowledge
      than those who did not.

PMID- 25966729
TI  - Which is the most effective disinfection method in primary root canals:
      Conventional or newly developed ones?
AB  - BACKGROUND: The aim of the study was to evaluate the antimicrobial activity of
      the-potassium-titanyl-phosphate--the KTP laser and ozone in of primary root
      canals. MATERIALS AND METHODS: Sixty primary incisor teeth were selected. The
      specimens were inoculated with 10 mL Enterococcus faecalis (E. faecalis). Groups:
      The KTP laser (1,5 W); gaseous ozone (150 s); sodium hypochlorite (NaOCl); saline
      group. Sterile paper points used to sample bacteria from the canals to tubes
      containing 5 mL of brain heart infusion broth. Then, 10 mL suspension was
      incubated in culture media for 24 h. Data were analyzed statistically using
      Kruskal-Wallis and Mann-Whitney U-test. RESULTS: There were statistically
      significant differences between all groups (P<0.05). Complete sterilization was
      achieved in the 2.5% NaOCl group. The number of bacteria were significantly
      reduced in experimental groups in comparison to the saline group. CONCLUSION: The
      KTP laser and ozone application provided a significant antibacterial effect in
      primary root canals; however, 2.5% NaOCl was superior.

PMID- 25966730
TI  - Availability and functionality of sphygmomanometers at health care institutions
      in Enugu, Nigeria.
AB  - OBJECTIVE: Our aim was to investigate the availability of functional blood
      pressure monitors at health care institutions in Enugu, Nigeria. METHODS: During
      repeated surveys of 15 (primary, secondary and tertiary) health care institutions
      in Enugu between 2007 and 2012, records were made of the availability and
      functional status of sphygmomanometers in the clinics and wards. We also assessed
      the degree of agreement between measurements by institutional staff and
      measurements by trained observers using the same or the standard
      sphygmomanometer. RESULTS: Apart from three institutions, there was inadequate
      availability of fully functional sphygmomanometers: 61 staff attending to
      outpatients were sharing 35 sphygmomanometers, 6 of which were faulty i.e.
      needing repairs. Wards invariably had only one or two functional
      sphygmomanometers, regardless of bed occupancy. Institutional staff ignored
      recommended guidelines for blood pressure measurement. The overall mean
      difference in blood pressure measurements between institutional staff and a
      trained observer (1.6 mmHg; 95% confidence interval, CI: -0.3 to 3.4; P=0.1) was
      greater and more significant than the mean difference between the two observers
      (0.1 mmHg; CI: -1.5 to 1.7; P=0.9) and the mean difference between institutional
      and standard sphygmomanometers (-0.2 mmHg; CI: -1.7 to 1.3; P=0.8). CONCLUSION:
      There has been a notable lack of reporting on the availability of blood pressure
      measuring devices in third world health care institutions. Our surveys have shown
      inadequate availability of functional sphygmomanometers in the institutions, but
      satisfactory agreement between measurements by institutional staff and trained
      observers. In view of recent guidelines and recommendations, there is need to
      supplement office readings with mercury devices with oscillometric home or
      automated office blood pressure recording.

PMID- 25966731
TI  - Holdaway's analysis of the nose prominence of an adult Nigerian population.
AB  - BACKGROUND: Facial beauty is a function of harmonious balance among all parts of
      the face, and the nose plays a dominant role in this because of its location
      exactly in the middle of the face. Therefore, an evaluation of the nasal form and
      its position relative to other facial structures should play an important part in
      the assessment of patients before orthognathic surgery, rhinoplasty or
      orthodontics. AIM: The aim was to establish normative values for the nose
      prominence of an adult Nigerian population using Holdaway's soft tissue
      cephalometric analysis. METHODOLOGY: Lateral cephalometric radiographs of 100
      adults aged 18-25 years, with normal occlusion and a harmonious facial appearance
      were analyzed. The nose prominence was assessed using Holdaway's analysis. Twenty
      radiographs randomly selected, were retraced to assess for errors. Data analysis
      included descriptive statistics, Student's t-tests and analysis of variance using
      the Statistical Package for Social Sciences. RESULTS: The mean value recorded for
      the nose prominence of the study population was 3.49 mm (standard deviation [SD],
      3.26 mm), with a range of -5.0 mm to 15.0 mm. Mean values obtained for females
      were 3.73 mm (SD, 2.88 mm) and males 3.19 mm (SD, 3.70 mm). No statistically
      significant gender difference was observed (P>0.05). In addition, no significant
      difference was observed between the nose prominence values recorded for different
      age-groups (P>0.05). CONCLUSION: Normative values were established for the nose
      prominence of an adult Nigerian population. The values obtained for Nigerians in
      this study are comparatively lower than that reported for other populations.
      These values would aid in treatment planning for orthognathic surgery,
      rhinoplasty and orthodontics in Nigerians.

PMID- 25966732
TI  - Pattern of hormone receptors and human epidermal growth factor receptor 2 status
      in sub-Saharan breast cancer cases: Private practice experience.
AB  - INTRODUCTION: Breast cancer is the most common cancer among women globally. With
      immunohistochemistry (IHC), breast cancer is classified into four groups based on
      IHC profile of estrogen receptor (ER)/progesterone receptor (PR) and human
      epidermal growth factor receptor 2 (HER2/neu) expression, positive (+) and/or
      negative (-). The IHC classification correlates well with intrinsic gene
      expression microarray categorization. ER-positive tumors may benefit from being
      treated with selective ER modulators and aromatase inhibitors, whereas patients
      with HER2/neu positive tumors have been shown to experience a significant
      survival advantage when treated with humanized monoclonal antibodies against
      HER2/neu. OBJECTIVE: To determine ER/PR, HER2/neu expression and their
      association with histological prognostic markers in female breast carcinomas seen
      in a private diagnostic laboratory based in Lagos. MATERIALS AND METHODS:
      Immunohistochemistry reports of breast cancer patients, which were diagnosed by
      histopathology section of a private diagnostic laboratory based in Lagos, Nigeria
      from August 2009 to August 2014. RESULTS: About 18.7% of breast cancers had IHC
      (ER, PR and HER2) done on them and were all females. The mean age of all subjects
      was 49.5 years (standard deviation, 13.2; range, 29-78 years). Most (95.8%) of
      the breast cancers were of invasive ductal carcinoma type, with 77.4% of them
      been >5 cm. IHC pattern was as follows: ER/PR+, HER2-=19 (39.6%), ER/PR-, HER2-
      (triple negative [TN])=14 (29.2%), ER/PR+, HER2+=9 (18.8%), ER/PR-, HER2+=6
      (12.5%), corresponding to Lumina A, TN/basal-like, Lumina B and HER2 over
      expressed respectively. CONCLUSION: Triple negative breast cancers are common in
      our environment and affect young females most and could be contributory to the
      poorer prognosis of breast cancer in our environment.

PMID- 25966733
TI  - Comprehensive dental management in a Hallermann-Streiff syndrome patient with
      unusual radiographic appearance of teeth.
AB  - Hallermann-Streiff syndrome (HSS) is a genetic disorder characterized by
      proportionate dwarfism, birdlike facies, hypotrichosis, skin atrophy, dyscephaly,
      bilateral microphthalmia, congenital cataracts, a narrow, weak, beaked nose, a
      hypoplastic mandible, and orodental anomalies. Occurrence is sporadic and
      distinct patterns of inheritance have not been found. This case report describes
      the dental management of a 3-year-old girl patient with HSS, who had unusual
      radiographic appearance of teeth. Furthermore, dental treatments and a 30-month
      follow-up period of the patient with this rare tooth structure malformation have
      been presented. 

PMID- 25966734
TI  - Multiple tooth anomalies in a nonsyndromic patient with class II division 2
      malocclusions: A case report and a literature review.
AB  - Reports in the literature about the craniofacial characteristics of patients with
      class II division 2 malocclusions show a lot of different patterns accompanied by
      palatally displaced upper incisors, congenital missing teeth, polydiastema,
      fusion, germination, tooth impaction, peg-shaped lateral incisors, persistent
      teeth, hypodontia, persistent deciduous teeth, transpositions, and supernumerary
      teeth. The following case report focuses on the description of the clinical
      characteristics observed on a patient with a very unusual conjunction of dental
      and skeletal anomalies mentioned above, as well as a literature review on the
      related issues. Extra-intra-oral examinations, radiographic evaluations,
      orthodontic consultation, and reviewing the literature concluded that this
      nonsyndromic patient that refused to receive all dental treatment approaches is
      special with its uniqueness. 

PMID- 25966735
TI  - Machete-cut injuries are occurring in the maxillofacial region in Zaria, Nigeria.
AB  - Five cases of machete cut injuries to the maxillofacial region seen over a period
      of 8 months (January-September, 2012), at the Maxillofacial Unit of Ahmadu Bello
      University Teaching Hospital, Zaria, Nigeria, are presented. The severity of the
      injuries is evident from the extent of tissue disruption as shown in the
      pictures. The immediate threats to life in the cases were hemorrhage and airway
      obstruction. Surgical repairs were performed under local anesthetic infiltration
      in three cases while the rest were performed under general anesthesia. There was
      no nerve repair done due to lack of facilities, although, adequate apposition of
      soft and hard tissues were achieved. Four patients had rapid postoperative
      recovery in our facility while one absconded after wound debridement and repair
      was achieved. Two patients who had nerve injuries were followed-up to monitor
      recovery of the injured nerves. There was no tetanus, gangrene, pseudoaneurysm or
      death recorded in our cases. There is a need for relevant authorities to check
      the occurrence of this kind of injury, especially as the weapon used is a house
      hold tool, which is readily available and accessible to all and sundry. 

PMID- 25966736
TI  - Diagnosis of acute myeloid leukemia in a dental hospital; report of a case with
      severe gingival hypertrophy.
AB  - Acute myeloid leukemias (AMLs) are aggressive hematopoietic neoplasms that, if
      untreated, can lead to death within days. Owing to its high morbidity rate, early
      diagnosis and appropriate medical therapy is essential. Oral lesions may be the
      presenting feature of acute leukemias and are, therefore, important diagnostic
      indicators of the disease. Erythematous or cyanotic gingival hyperplasia with or
      without necrosis is reported to be the most consistent symptom leading to a
      diagnosis of acute leukemia that directs the patient to seek early dental
      consultation. This report refers to a patient with AML that was provisionally
      diagnosed in the dental hospital due to severe gingival enlargements. 

PMID- 25966738
TI  - Fasting plasma triglyceride concentration: A possible approach to identify
      increased risk of statin-induced type 2 diabetes.
AB  - AIM: To evaluate the hypothesis that measurement of fasting plasma triglyceride
      concentration identifies individuals at enhanced risk of statin-induced type 2
      diabetes mellitus. METHODS: A retrospective analysis of data collected from
      routine health examinations in non-diabetic, East Asian individuals (n = 5790)
      with low-density lipoprotein cholesterol concentrations of ?3.4 mmol/L. Subjects
      were stratified into those with or without a triglyceride concentration of ?1.7
      mmol/L, and comparisons made of risk factors for type 2 diabetes mellitus.
      RESULTS: Approximately 40% of men and 20% of women with elevations of both low
      density lipoprotein cholesterol and triglyceride concentrations were more insulin
      resistant (homeostatic model assessment of insulin resistance), associated with
      higher plasma concentrations of HbA1c, glucose and insulin. CONCLUSION:
      Apparently, healthy, non-diabetic East Asian men and women with combined
      elevations of low-density lipoprotein cholesterol and triglyceride concentrations
      are glucose intolerant and insulin resistant, and thereby at enhanced risk of
      type 2 diabetes mellitus. Measurement of plasma triglyceride concentration can
      identify within a hypercholesterolemic population a subset of individuals at
      enhanced risk of statin-induced type 2 diabetes mellitus.

PMID- 25966737
TI  - M1 and M2 macrophage proteolytic and angiogenic profile analysis in
      atherosclerotic patients reveals a distinctive profile in type 2 diabetes.
AB  - This study aimed to investigate atherosclerotic mediators' expression levels in
      M1 and M2 macrophages and to focus on the influence of diabetes on M1/M2
      profiles. Macrophages from 36 atherosclerotic patients (19 diabetics and 17 non
      diabetics) were cultured with interleukin-1beta (IL-1beta) or IL-4 to induce M1
      or M2 phenotype, respectively. The atherosclerotic mediators' expression was
      evaluated by quantitative reverse transcription-polymerase chain reaction (RT
      PCR). The results showed that M1 and M2 macrophages differentially expressed
      mediators involved in proteolysis and angiogenesis processes. The proteolytic
      balance (matrix metalloproteinase-9 (MMP-9)/tissue inhibitor of metalloproteinase
      1 (TIMP-1), MMP-9/plasminogen activator inhibitor-1 (PAI-1) and MMP-9/tissue
      factor pathway inhibitor-2 (TFPI-2) ratios) was higher in M1 versus M2, whereas
      M2 macrophages presented higher angiogenesis properties (increased vascular
      endothelial growth factor/TFPI-2 and tissue factor/TFPI-2 ratios). Moreover, M1
      macrophages from diabetics displayed more important proangiogenic and proteolytic
      activities than non-diabetics. This study reveals that M1 and M2 macrophages
      could differentially modulate major atherosclerosis-related pathological
      processes. Moreover, M1 macrophages from diabetics display a deleterious
      phenotype that could explain the higher plaque vulnerability observed in these
      subjects. 

PMID- 25966739
TI  - Persistent dilemmas in zoster eye disease.
AB  - Herpes zoster ophthalmicus (HZO) is a common, vision and potentially life
      threatening disease caused by the reactivation of the varicella-zoster virus
      (VZV) in the distribution of the first division of cranial nerve V. Although the
      rate of herpes zoster increases with age, over half of the people with zoster in
      general, including HZO, are under age 60. In addition, over 90% of people with
      zoster are immunocompetent, even though the disease is more common and severe in
      immunocompromised patients. The incidence of zoster is increasing worldwide for
      unknown reasons. The epidemiology has not yet been impacted by the zoster vaccine
      (ZV). The lack of a strong recommendation by physicians for this vaccine is a
      major barrier to its use. An unresolved dilemma regards the optimum timing for
      this vaccine. In the USA, the current recommendation by the Centers for Disease
      Control and Prevention (CDC) is for eligible people age 60 and older, despite its
      greater efficacy in reducing the incidence of disease and Food and Drug
      Administration (FDA) approval for age 50-59. Although there is a consensus
      regarding use of acute high-dose oral antiviral treatment to reduce ocular
      complications, there is limited evidence for prolonged treatment. The rationale
      for a proposed randomised controlled trial (RCT) of suppressive antiviral
      treatment to reduce chronic eye disease and postherpetic neuralgia (PHN) includes
      evidence that zoster is followed by chronic active VZV infection and similarities
      between HZO and herpes simplex virus (HSV) eye infection, where this treatment is
      effective and is the standard of care. 

PMID- 25966740
TI  - Recovery of plasma vascular endothelial growth factor concentrations during
      aflibercept loading phase and after the transition to bimonthly treatment for
      neovascular age-related macular degeneration.
AB  - AIMS: To provide data on plasma vascular endothelial growth factor (VEGF)
      concentration during three consecutive monthly intravitreal aflibercept
      injections and after transition to bimonthly treatment in patients with
      neovascular age-related macular degeneration (nAMD). METHODS: Sixteen consecutive
      treatment-naive Caucasian patients with nAMD were included in the study. The
      treatment consisted of one intravitreal aflibercept (2 mg) injection every 28
      days for three consecutive months followed by a fourth injection 8 weeks later.
      VEGF plasma concentrations were measured with Luminex on day 0 (baseline, prior
      to first injection); days 1, 6 and 27 (prior to second injection); day 55 (prior
      to third injection) and days 97 and 111 (after third injection). RESULTS:
      Baseline plasma VEGF concentration was 59.6+/-13.3 pg/mL. Aflibercept decreased
      plasma VEGF concentration to 32.5+/-3 pg/mL on day 1 (p<0.0001) and 34.7+/-6.3
      pg/mL on day 6 (p<0.0001). On day 27, the VEGF plasma level increased to 50.6+/
      6.5 pg/mL (p=0.009) and on day 55 to 52.8+/-8.8 pg/mL (p=0.027). There was no
      statistically significant difference between mean plasma VEGF concentrations on
      days 27 and 55 (p=0.139). Plasma VEGF concentration recovered completely 6 weeks
      after the third injection, reaching 57.9+/-9.6 pg/mL on day 97 (p=0.600) and
      59.5+/-11.6 pg/mL on day 111 (p=0.987). CONCLUSIONS: Intravitreal aflibercept
      decreases plasma VEGF concentration mostly in the first week after treatment.
      Despite repeated monthly intravitreal injections, there was a monthly increase in
      plasma VEGF values to near baseline levels, with complete recovery 6 weeks after
      the third injection. TRIAL REGISTRATION NUMBER: Identifier no. NCT02125864.

PMID- 25966742
TI  - Ginsenoside rh2 inhibits cancer stem-like cells in skin squamous cell carcinoma.
AB  - BACKGROUND/AIMS: Treatments targeting cancer stem cells (CSCs) are most effective
      cancer therapy, whereas determination of CSCs is challenging. We have recently
      reported that Lgr5-positive cells are cancer stem cells (CSCs) in human skin
      squamous cell carcinoma (SCC). Ginsenoside Rh2 (GRh2) has been shown to
      significantly inhibit growth of some types of cancers, whereas its effects on the
      SCC have not been examined. METHODS: Here, we transduced human SCC cells with
      lentivirus carrying GFP reporter under Lgr5 promoter. The transduced SCC cells
      were treated with different doses of GRh2, and then analyzed cell viability by
      CCK-8 assay and MTT assay. The effects of GRh2 on Lgr5-positive CSCs were
      determined by fow cytometry and by tumor sphere formation. Autophagy-associated
      protein and beta-catenin were measured by Western blot. Expression of short
      hairpin small interfering RNA (shRNA) for Atg7 and beta-catenin were used to
      inhibit autophagy and beta-catenin signaling pathway, respectively, as loss-of
      function experiments. RESULTS: We found that GRh2 dose-dependently reduced SCC
      viability, possibly through reduced the number of Lgr5-positive CSCs. GRh2
      increased autophagy and reduced beta-catenin signaling in SCC cells. Inhibition
      of autophagy abolished the effects of GRh2 on beta-catenin and cell viability,
      while increasing beta-catenin abolished the effects of GRh2 on autophagy and cell
      viability. CONCLUSION: Taken together, our data suggest that GRh2 inhibited SCC
      growth, possibly through reduced the number of Lgr5-positive CSCs. This may be
      conducted through an interaction between autophagy and beta-catenin signaling.

PMID- 25966741
TI  - Damage-Associated Molecular Patterns in the Course of Lung Cancer--A Review.
AB  - More than 20 years ago, the 'danger theory' was proposed which explains why
      potent immune responses with no microbial components are elicited against tissue
      transplants, injuries, tumours and autoimmune diseases. It states that the immune
      system can distinguish between dangerous and innocuous endogenous signals. In
      response to trauma or other types of tissue and cell damage, certain molecules
      that function inside the cell are released or secreted from damaged or dying
      cells. Such mechanisms initiate an immune response in the absence of infection.
      These immunostimulatory molecules were named damage-associated molecular patterns
      (DAMPs). In this article, we will review the available data on the influence of
      select DAMPs on lung cancer cells and tumour microenvironments. We will also
      summarize the current information regarding the interactions between lung cancer
      associated DAMPs and their toll-like receptors.

PMID- 25966743
TI  - The Dynamic cerebral autoregulatory adaptive response to noradrenaline is
      attenuated during systemic inflammation in humans.
AB  - Vasopressor support is used widely for maintaining vital organ perfusion pressure
      in septic shock, with implications for dynamic cerebral autoregulation (dCA).
      This study investigated whether a noradrenaline-induced steady state increase in
      mean arterial blood pressure (MAP) would enhance dCA following lipopolysaccharide
      (LPS) infusion, a human-experimental model of the systemic inflammatory response
      during early sepsis. The dCA in eight healthy males was examined prior to and
      during an intended noradrenaline-induced MAP increase of approximately 30 mmHg.
      This was performed at baseline and repeated after a 4-h intravenous LPS infusion.
      The assessments of dCA were based on transfer function analysis of spontaneous
      oscillations between MAP and middle cerebral artery blood flow velocity measured
      by transcranial Doppler ultrasound in the low frequency range (0.07-0.20 Hz).
      Prior to LPS, noradrenaline administration was associated with a decrease in gain
      (1.18 (1.12-1.35) vs 0.93 (0.87-0.97) cm/mmHg per s; P < 0.05) with no effect on
      phase (0.71 (0.93-0.66) vs 0.94 (0.81-1.10) radians; P = 0.58). After LPS,
      noradrenaline administration changed neither gain (0.91 (0.85-1.01) vs 0.87 (0.81
      0.97) cm/mmHg per s; P = 0.46) nor phase (1.10 (1.04-1.30) vs 1.37 (1.23-1.51)
      radians; P = 0.64). The improvement of dCA to a steady state increase in MAP is
      attenuated during an LPS-induced systemic inflammatory response. This may suggest
      that vasopressor treatment with noradrenaline offers no additional
      neuroprotective effect by enhancing dCA in patients with early sepsis.

PMID- 25966744
TI  - Reactivation of Giardia lamblia cysts after exposure to low-pressure UV
      irradiation.
AB  - In this study, we determined the repair capabilities of Giardia lamblia cysts
      when they were exposed to low-pressure (LP) UV and then 4 different repair
      conditions. A UV collimated beam apparatus was used to expose shallow suspensions
      of G. lamblia cysts in buffered reagent water (PBS, pH 7.2) to various doses of
      LP UV irradiation. After UV irradiation, samples were exposed to 4 repair
      conditions (light and dark repair conditions with 2 temperatures (25  degrees C
      and 37  degrees C) for each condition). The inactivation of G. lamblia cysts by
      LP UV was very extensive (~ 5 log10) even with a low dose of LP UV (1 mJ/cm(2)).
      More importantly, there was significant restoration of infectivity in G. lamblia
      cysts when they were exposed to a low dose of LP UV and then to all the repair
      conditions tested. Overall, the results of this study indicate that G. lamblia
      cysts do have the ability to repair their UV-damaged DNA when they are exposed to
      low doses of LP UV irradiation. This is the first study to report the presence of
      repair in UV-irradiated G. lamblia cysts.

PMID- 25966745
TI  - Targeted Intracellular Controlled Drug Delivery and Tumor Therapy through in Situ
      Forming Ag Nanogates on Mesoporous Silica Nanocontainers.
AB  - Targeting nanocontainers to the pathological zone and controlling release of
      their cargoes, in particular delivery of anticancer drugs to specific tumor cells
      in a targeted and controlled manner, remain the key challenges in drug delivery.
      This paper reports the development of a traceable and tumor-targeted
      intracellular drug release nanocontainer. The nanocontainer is obtained by in
      situ growth of silver nanoparticles (AgNPs) on the surfaces of mesoporous silica
      nanospheres (MSNs) using a DNA-templated process. Additionally, drug release from
      the nanopores is achieved by selective glutathione (GSH)-triggered dismantle of
      the AgNPs, and the concurrent fluorescence change allows real-time monitoring of
      drug release efficacy and facile visualization of in vivo delivery events. After
      being functionalized with sgc8 aptamer on the outer shell of the AgNPs, the
      targeted nanocontainers are delivered into acute lymphoblastic leukemia cells by
      aptamer-mediated recognition and endocytosis. Moreover, the GSH-responsive
      process presents an improvement in the cell-specific drug release and
      chemotherapeutic inhibition of tumor growth. 

PMID- 25966747
TI  - Maxillary molar distalization therapy in adult patients: a multicentre study.
AB  - OBJECTIVES: To evaluate dento-skeletal changes following conventional anchorage
      molar distalization therapy in adult patients. SETTING AND SAMPLE POPULATION:
      Thirty-three patients (25 women, mean age 23 years 1 months +/- 3 months; 8 men,
      mean age 28 years 3 months +/- 7 months) were recruited from 4 Board Certified
      specialists. All subjects underwent molar distalization therapy using intra-oral
      distalizing appliances. SUBJECTS AND METHODS: Cephalometric headfilms were
      available for all subjects before (T1) and at the end of comprehensive treatment
      (T2). The initial and final measurements and treatment changes were compared by
      means of a paired t-test. RESULTS: Mean total treatment time was 3 years 2 months
      +/- 6 months. Maxillary first molar distalized 2.9 +/- 0.6 mm contributing 64.4%
      to Class II molar correction, whereas mandibular first molar showed a concomitant
      mesial movement of 1.6 +/- 0.5 mm. Maxillary incisors retroclined an average of
      5.8 degrees  +/- 3.9 degrees , lower incisors proclined 4.1 degrees  +/- 1.1
      degrees  and the occlusal plane rotated downwards and backwards 1.8 degrees  +/-
      2.1 degrees . Clockwise rotation of the mandible (1.7 degrees  +/- 0.5 degrees )
      and increase in lower facial height (2.5 +/- 1.5 mm) were also observed.
      CONCLUSIONS: Maxillary molar distalization therapy can be successfully performed
      in adult patients despite a slight increase in vertical facial dimension should
      be considered.

PMID- 25966746
TI  - The effect of orally administered ranitidine and once-daily or twice-daily orally
      administered omeprazole on intragastric pH in cats.
AB  - BACKGROUND: Gastric acid suppressants frequently are used in cats with acid
      related gastric disorders. However, it is not known if these drugs effectively
      increase intragastric pH in cats. OBJECTIVES: To examine the effects of PO
      administered ranitidine and omeprazole on intragastric pH in cats and to compare
      the efficacy of once-daily versus twice-daily dosage regimens for omeprazole.
      ANIMALS: Eight domestic shorthair cats. METHODS: Using a randomized 4-way cross
      over design, cats were given enteric-coated omeprazole granules (1.1-1.3 mg/kg
      q24h and q12h), ranitidine (1.5-2.3 mg/kg q12h), and placebo. Intragastric pH was
      monitored continuously for 96 hours using the Bravo(TM) system, starting on day 4
      of treatment, followed by a median washout period of 12 days. Mean percentage of
      time pH was >=3 and >=4 was compared among groups using repeated measures ANOVA.
      RESULTS: Mean +/- SD percentage of time intragastric pH was >=3 and >=4 was 67.0
      +/- 24.0% and 54.6 +/- 26.4% for twice-daily omeprazole, 24.4 +/- 22.8% and 16.8
      +/- 19.3% for once-daily omeprazole, 16.5 +/- 9.0% and 9.6 +/- 5.9% for
      ranitidine, and 9.4 +/- 8.0% and 7.0 +/- 6.6% for placebo administration. Twice
      daily omeprazole treatment significantly increased intragastric pH, whereas pH
      after once-daily omeprazole and ranitidine treatments did not differ from that of
      placebo-treated cats. CONCLUSION AND CLINICAL IMPORTANCE: Only twice-daily PO
      administered omeprazole significantly suppressed gastric acidity in healthy cats,
      whereas once-daily omeprazole and standard dosages of ranitidine were not
      effective acid suppressants in cats.

PMID- 25966748
TI  - Transient renal Fanconi syndrome in a Chihuahua exposed to Chinese chicken jerky
      treats.
AB  - Transient Fanconi syndrome without azotemia was diagnosed in a dog and was
      associated with ingestion of Chinese chicken jerky treats. Fanconi syndrome is a
      proximal renal tubular defect and a diagnosis was made based upon severe
      glucosuria with normoglycemia, and severe generalized aminoaciduria. The clinical
      signs of polyuria and polydipsia as well as the massive urinary metabolic
      abnormalities resolved after jerky treat withdrawal. While frequently seen in
      North America and Australia, this is the first report of jerky treat induced
      Fanconi syndrome in continental Europe. Clinicians should be aware of this
      potential intoxication and be vigilant for a history of jerky treat consumption
      in a dog with glucosuria. 

PMID- 25966749
TI  - Physical fitness and physical activity in fatigued and non-fatigued inflammatory
      bowel disease patients.
AB  - OBJECTIVE: To assess physical fitness and physical activity in inflammatory bowel
      disease (IBD) patients and whether fatigue is associated with impaired physical
      fitness and impaired physical activity. MATERIALS AND METHODS: Ten patients with
      quiescent IBD and fatigue (fatigue group [FG]) based on the Checklist Individual
      Strength-Fatigue score of >=35 were matched for age (+/-5 years) and sex with a
      non-fatigue group (NFG) with IBD. Physical fitness was measured with a cyclo
      ergometric-based maximal exercise test, a submaximal 6-min walk test, and a
      dynamometer test to quantify the isokinetic muscle strength of the knee extensors
      and flexors. Level of physical activity was measured with an accelerometer-based
      activity monitor. RESULTS: The patients in both groups did not differ in regard
      to medication use, clinical characteristics, and body composition. However,
      medium-to-large effect sizes for impaired physical fitness (both
      cardiorespiratory fitness and muscle strength) and physical activity were seen
      between the patients in the FG and the NFG. Especially, intensity of physical
      activity was significantly lower in the FG patients compared with the NFG
      patients (effect size: 1.02; p = 0.037). Similar results were seen when outcomes
      of the FG and NFG were compared with reference values of the normal population.
      CONCLUSION: Fatigued IBD patients show an impaired physical fitness and physical
      activity compared with non-fatigued IBD patients. This gives directions for a
      physical component in fatigue in IBD patients. Therefore, these new insights into
      fatigue indicate that these patients might benefit from an exercise program to
      improve physical fitness and physical activity.

PMID- 25966750
TI  - The Benefit Risk Assessment of Consumption of Marine Species Based on Benefit
      Risk Analysis for Foods (BRAFO)-tiered Approach.
AB  - OBJECTIVE: To assess the net health effect caused by the consumption of specific
      marine species based on Benefit-Risk Analysis for Foods (BRAFO)-tiered approach.
      METHODS: Twenty species were collected from the Zhoushan Archipelago, China.
      Concentrations of n-3 long-chain polyunsaturated fatty acids, methyl mercury
      (MeHg), and dioxin-like compounds (DLCs) in the samples were analyzed for benefit
      risk assessment based on BRAFO-tiered approach. RESULTS: Based on the BRAFO
      tiered approach, reference scenario (no intake) and alternative scenario (intake
      of specific species of 200 g/week) were determined. The exposure to MeHg/DLCs via
      alternative scenario of all studied species did not exceed provisional tolerable
      weekly/monthly intake. However, the adult population with high DLCs exposure in
      China would significantly exceed the upper limit of DLCs via an additional
      alternative scenario of some species such as Auxis thazard. The results of
      deterministic computation showed that alternative scenario of all studied species
      generated clear net beneficial effects on death prevention and child IQ gain.
      CONCLUSION: The alternative scenario of all studied species could be recommended
      to population with average DLCs exposure, and the reference scenario of species
      with relatively high DLCs concentration could be recommended to population
      exposed to high DLCs.

PMID- 25966751
TI  - Carbon Monoxide Releasing Molecule Accelerates Reendothelialization after Carotid
      Artery Balloon Injury in Rat.
AB  - OBJECTIVE: This study was aimed to investigate the effects of carbon monoxide
      releasing molecule (CORM-2), a novel carbon monoxide carrier, on the
      reendothelialization of carotid artery in rat endothelial denudation model.
      METHODS: Male rats subjected to carotid artery balloon injury were treated with
      CORM-2, inactive CORM-2 (iCORM-2) or dimethyl sulfoxide (DMSO). The
      reendothelialization capacity was evaluated by Evans Blue dye and the
      immunostaining with anti-CD31 antibody. The number of circulating endothelial
      progenitor cells (EPCs) was detected by flow cytometry. The proliferation,
      migration, and adhesion of human umbilical vein endothelial cells (HUVECs) were
      assessed by using [3H]thymidine, Boyden chamber and human fibronectin
      respectively. The expressions of protein were detected by using western blot
      analysis. RESULTS: CORM-2 remarkably accelerated the re-endothelialization 5 d
      later and inhibited neointima formation 28 d later. In addition, the number of
      peripheral EPCs significantly increased in CORM-2-treated rats than that in iCORM
      2 or DMSO-treated rats after 5 d later. In vitro experiments, CORM-2
      significantly enhanced the proliferation, migration and adhesion of HUVECs. The
      levels of Akt, eNOS phosphorylation, and NO generation in HUVECs were also much
      higher in CORM-2 treated group. Blocking of PI3K/Akt/eNOS signaling pathway
      markedly suppressed the enhanced migration and adhesion of HUVECs induced by CORM
      2. CONCLUSION: CORM-2 could promote endothelial repair, and inhibit neointima
      formation after carotid artery balloon injury, which might be associated with the
      function changes of HUVECs regulated by PI3K/Akt/eNOS pathway.

PMID- 25966752
TI  - High Physical Activity is Associated with an Improved Lipid Profile and Resting
      Heart Rate among Healthy Middle-aged Chinese People.
AB  - OBJECTIVE: To investigate the effects of physical activity (PA) on dyslipidemia
      and elevated resting heart rate (RHR) in a large-scale cross-sectional study in
      China. METHODS: We recruited community-based individuals who were 40-60 years old
      using a cluster sampling method. The PA levels of the participants were
      classified as low, moderate, or high, using the International Physical Activity
      Questionnaire. Dyslipidemia was defined as the detection of abnormalities in
      lipid indicators, and 4 lipid parameters were evaluated using fasting blood
      samples. Multivariate logistic regression analyses were used to evaluate the
      associations of PA with dyslipidemia and RHR. RESULTS: A total of 10,321
      participants (38.88% men) were included in this study. The percentages of
      individuals with high, moderate, and low PA levels were 46.5%, 43.9%, and 9.6%,
      respectively. In both men and women, high PA provided odds ratios of 0.88 [95%
      confidence interval (CI): 0.83, 0.94] for dyslipidemia and 0.82 (95% CI: 0.73,
      0.92) for elevated RHR, compared to participants with low PA. CONCLUSION: Our
      data suggested that substantial health benefits (related to dyslipidemia and
      elevated RHR) occurred at higher intensity PA, with greater energy consumption,
      in middle-aged Chinese people, and particularly in men.

PMID- 25966753
TI  - Grape Seed Proanthocyanidin Extract Alleviates Arsenic-induced Oxidative
      Reproductive Toxicity in Male Mice.
AB  - OBJECTIVE: To determine the ability of grape seed proanthocyanidin extract (GSPE)
      in alleviating arsenic-induced reproductive toxicity. METHODS: Sixty male Kunming
      mice received the following treatments by gavage: normal saline solution
      (control); arsenic trioxide (ATO; 4 mg/kg); GSPE (400 mg/kg); ATO+GSPE (100
      mg/kg); ATO+GSPE (200 mg/kg) and ATO+GSPE (400 mg/kg). Thereafter, the mice were
      sacrificed and weighed, and the testis was examined for pathological changes.
      Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase 1 (HO1),
      glutathione S-transferase (GST), NAD(P)H dehydrogenase, and quinone 1 (NQO1)
      expression in the testis was detected by real-time PCR. Superoxide dismutase
      (SOD), glutathione (GSH), total antioxidative capability (T-AOC), malondialdehyde
      (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reproductive indexes were analyzed.
      RESULTS: ATO-treated mice showed a significantly decreased sperm count and testis
      somatic index and activity levels of SOD, GSH, and T-AOC than control group.
      Compared to the ATO-treated group, ATO +GSPE group showed recovery of the
      measured parameters. Mice treated with ATO+high-dose GSPE showed the highest
      level of mRNA expression of Nrf2, HO, NQO1, and GST. CONCLUSION: GSPE alleviates
      oxidative stress damage in mouse testis by activating Nrf2 signaling, thus
      counteracting arsenic-induced reproductive toxicity.

PMID- 25966754
TI  - Neurobehavioral Assessment of Rats Exposed to Yttrium Nitrate during Development.
AB  - OBJECTIVE: The aim of this study was to assess the effects of yttrium nitrate on
      neurobehavioral development in Sprague-Dawley rats. METHODS: Dams were orally
      exposed to 0, 5, 15, or 45 mg/kg daily of yttrium nitrate from gestation day (GD)
      6 to postnatal day (PND) 21. Body weight and food consumption were monitored
      weekly. Neurobehavior was assessed by developmental landmarks and reflexes, motor
      activity, hot plate, Rota-rod and cognitive tests. Additionally, brain weights
      were measured on PND 21 and 70. RESULTS: No significant difference was noted
      among all groups for maternal body weight and food consumption. All yttrium
      exposed offspring showed an increase in body weight on PND 21; however, no
      significant difference in body weight for exposed pups versus controls was
      observed 2 weeks or more after the yttrium solution was discontinued. The groups
      given 5 mg/kg daily decreased significantly in the duration of female forelime
      grip strength and ambulation on PND 13. There was no significant difference
      between yttrium-exposed offspring and controls with respect to other behavioral
      ontogeny parameters and postnatal behavioral test results. CONCLUSION: Exposure
      of rats to yttrium nitrate in concentrations up to 45 mg/kg daily had no adverse
      effects on their neurobehavioral development.

PMID- 25966755
TI  - Effect of Dietary Resistant Starch on Prevention and Treatment of Obesity-related
      Diseases and Its Possible Mechanisms.
AB  - Overweight or obesity has become a serious public health problem in the world,
      scientists are concentrating their efforts on exploring novel ways to treat
      obesity. Nowadays, the availabilities of bariatric surgery and pharmacotherapy
      have enhanced obesity treatment, but it should has support from diet, physical
      exercise and lifestyle modification, especially the functional food. Resistant
      starch, an indigestible starch, has been studied for years for its beneficial
      effects on regulating blood glucose level and lipid metabolism. The aim of this
      review is to summarize the effect of resistant starch on weight loss and the
      possible mechanisms. According to numerous previous studies it could be concluded
      that resistant starch can reduce fat accumulation, enhance insulin sensitivity,
      regulate blood glucose level and lipid metabolism. Recent investigations have
      focused on the possible associations between resistant starch and incretins as
      well as gut microbiota. Resistant starch seems to be a promising dietary fiber
      for the prevention or treatment of obesity and its related diseases. 

PMID- 25966756
TI  - Effects of Maternal Linseed Oil Supplementation on Metabolic Parameters in
      Cafeteria Diet-induced Obese Rats.
AB  - Because linseed oil may influence maternal and fetal metabolisms, we investigated
      its role in the modulation of lipid metabolism in cafeteria diet-induced obese
      rats and their offspring. Female Wistar rats were fed control or cafeteria food,
      which were either supplemented or not supplemented with linseed oil (5%) for 1
      month before and during gestation. At parturition, serum and tissue lipids and
      enzyme activities were analyzed. Cafeteria diet induced adverse metabolic
      alterations in both mothers and offspring. Linseed oil improved metabolic status.
      In conclusion, linseed oil displayed health benefits by modulating tissue enzyme
      activities in both obese mothers and their newborns. 

PMID- 25966757
TI  - Novel Association of Killer Cell Immunoglobulin-like Receptor Genes with EBV
      infectious Diseases in Children.
AB  - Killer cell immunoglobulin-like receptors (KIRs) which are mainly expressed on
      natural killer (NK) cells are implicated in many virus infections. However, it is
      unclear whether or not KIRs are associated with susceptibility to Epstein-Barr
      virus (EBV) infection related diseases. Therefore, the purpose of our study was
      to investigate possible correlation between polymorphisms of KIR genes and
      infectious mononucleosis (IM)/EBV-associated hemophagocytic lymphohistiocytosis
      (EBV-HLH). The polymorphisms of KIR genes were detected by polymerase chain
      reaction with sequence-specific primers (PCR-SSP). The results would contribute
      to clarify the association of KIRs with EBV induced diseases, and provide new
      insights into the role of NK cells and innate immune response against viral
      infections and/or subsequent progression. 

PMID- 25966758
TI  - Changing Grains for the Prevention and Treatment of Kashin-Beck Disease in
      Children: a Meta-analysis.
AB  - To evaluate the efficacy of changing grains on the prevention and treatment of
      Kashin-Beck Disease (KBD) in children, community-based trials were acquired from
      seven electronic databases (up to July 2014). As a result, the methodological
      quality of the six trials that have been included into our analysis was low. The
      pooled ORs favoring the prevention and treatment effects of changing grains were
      0.15 (95% CI: 0.03-0.70) and 2.13 (95% CI: 1.44-3.16) respectively by meta
      analysis. Subgroup analysis demonstrated the pooled OR favoring treatment effect
      of exchanging grains rather than drying grains both compared with endemic grains.
      The results showed that changing grains had obvious effects on the prevention and
      treatment of KBD in children. However, the evidences were limited by the
      potential biases and confounders. Large and well-designed trials are still
      needed. 

PMID- 25966759
TI  - Combination of Loop-Mediated Isothermal Amplification Assay and Nested PCR for
      Detection of Borrelia burgdorferi sensu lato in Human Serum Samples.
AB  - A set of universal loop-mediated isothermal amplification (LAMP) primers
      targeting the fla gene was designed to detect Borrelia burgdorferi sensu lato (B.
      burgdorferi s.l.) in human samples. The sensitivity of LAMP was 20
      copies/reaction, and the assay did not detect false positives among 11 other
      related bacteria. A positive LAMP result was obtained for 9 of the 24 confirmed
      cases and for 12 of 94 suspected cases. The positive rate of LAMP was the same as
      that of nested PCR. The LAMP is a useful diagnostic method that can be developed
      for rapid detection of B. burgdorferi s.l. in human sera. Combination of the LAMP
      and nested PCR was more sensitive for detecting B. burgdorferi s.l. in human
      serum samples. 

PMID- 25966760
TI  - External Bacterial Flora and Antimicrobial Susceptibility Patterns of
      Staphylococcus spp. and Pseudomonas spp. Isolated from Two Household Cockroaches,
      Blattella germanica and Blatta orientalis.
AB  - A study was performed to estimate the prevalence of the external bacterial flora
      of two domestic cockroaches (Blattella germanica and Blatta orientalis) collected
      from households in Tebessa (northeast Algeria). Three major bacterial groups were
      cultured (total aerobic, enterobacteria, and staphylococci) from 14 specimens of
      cockroaches, and antibiotic susceptibility was tested for both Staphylococcus and
      Pseudomonas isolates. Culturing showed that the total bacterial load of
      cockroaches from different households were comparable (P<0.001) and
      enterobacteria were the predominant colonizers of the insect surface, with a
      bacterial load of (2.1 * 105 CFU/insect), whereas the staphylococci group was the
      minority. Twenty-eight bacterial species were isolated, and susceptibility
      patterns showed that most of the staphylococci isolates were highly susceptible
      to chloramphenicol, gentamycin, pristinamycin, ofloxacin, clindamycin, and
      vancomycin; however, Pseudomonas strains exhibited resistance to
      amoxicillin/clavulanic acid, imipenem, and the second-generation antibiotic
      cephalosporin cefuroxime.

PMID- 25966762
TI  - Retraction. The Arabidopsis Malectin-Like Leucine-Rich Repeat Receptor-Like
      Kinase IOS1 Associates with the Pattern Recognition Receptors FLS2 and EFR and Is
      Critical for Priming of Pattern-Triggered Immunity. Plant Cell 26: 3201-3219.

PMID- 25966761
TI  - Arabidopsis CALCIUM-DEPENDENT PROTEIN KINASE8 and CATALASE3 Function in Abscisic
      Acid-Mediated Signaling and H2O2 Homeostasis in Stomatal Guard Cells under
      Drought Stress.
AB  - Drought is a major threat to plant growth and crop productivity. Calcium
      dependent protein kinases (CDPKs, CPKs) are believed to play important roles in
      plant responses to drought stress. Here, we report that Arabidopsis thaliana CPK8
      functions in abscisic acid (ABA)- and Ca(2+)-mediated plant responses to drought
      stress. The cpk8 mutant was more sensitive to drought stress than wild-type
      plants, while the transgenic plants overexpressing CPK8 showed enhanced tolerance
      to drought stress compared with wild-type plants. ABA-, H2O2-, and Ca(2+)-induced
      stomatal closing were impaired in cpk8 mutants. Arabidopsis CATALASE3 (CAT3) was
      identified as a CPK8-interacting protein, confirmed by yeast two-hybrid,
      coimmunoprecipitation, and bimolecular fluorescence complementation assays. CPK8
      can phosphorylate CAT3 at Ser-261 and regulate its activity. Both cpk8 and cat3
      plants showed lower catalase activity and higher accumulation of H2O2 compared
      with wild-type plants. The cat3 mutant displayed a similar drought stress
      sensitive phenotype as cpk8 mutant. Moreover, ABA and Ca(2+) inhibition of inward
      K(+) currents were diminished in guard cells of cpk8 and cat3 mutants. Together,
      these results demonstrated that CPK8 functions in ABA-mediated stomatal
      regulation in responses to drought stress through regulation of CAT3 activity. 

PMID- 25966765
TI  - Coagulation, Fibrinolysis and Inhibitors in Failing Filters during Continuous
      Venovenous Hemofiltration in Critically Ill Patients with Acute Kidney Injury:
      Effect of Anticoagulation Modalities.
AB  - INTRODUCTION: The mechanisms of early filter failure and clotting with different
      anticoagulation modalities during continuous venovenous hemofiltration (CVVH) are
      largely unknown. METHODS: Citrate, heparin and no anticoagulation were compared.
      Blood was drawn pre- and post filter up to 720 min. Concentrations of the
      thrombin-antithrombin (TAT), activated protein C-protein C inhibitor (APC-PCI),
      and type I plasminogen activator inhibitor (PAI-1) were determined. RESULTS: In
      case of early filter failure (<24 h), inlet concentrations of TAT and APC-PCI
      were higher over time, irrespective of anticoagulation. There was more production
      of APC-PCI and platelet-derived PAI-1 in the filter after 10 min in the heparin
      group than in other groups. In clotting filters, production of APC-PCI and PAI
      was also higher with heparin than citrate. CONCLUSION: Coagulation activation in
      plasma and inhibition of anticoagulation in plasma and filter may partly
      determine early CVVH filter failure due to clotting, particularly when heparin is
      used. Regional anticoagulation by citrate circumvents the inhibition of
      anticoagulation and fibrinolysis by platelet activation following heparin.

PMID- 25966764
TI  - The Choline/Ethanolamine Kinase Family in Arabidopsis: Essential Role of CEK4 in
      Phospholipid Biosynthesis and Embryo Development.
AB  - Phospholipids are highly conserved and essential components of biological
      membranes. The major phospholipids, phosphatidylethanolamine and
      phosphatidylcholine (PtdCho), are synthesized by the transfer of the
      phosphoethanolamine or phosphocholine polar head group, respectively, to the
      diacylglycerol backbone. The metabolism of the polar head group characterizing
      each phospholipid class is poorly understood; thus, the biosynthetic pathway of
      major phospholipids remains elusive in Arabidopsis thaliana. The
      choline/ethanolamine kinase (CEK) family catalyzes the initial steps of
      phospholipid biosynthesis. Here, we analyzed the function of the four CEK family
      members present in Arabidopsis. Knocking out of CEK4 resulted in defective embryo
      development, which was complemented by transformation of genomic CEK4. Reciprocal
      genetic crossing suggested that CEK4 knockout causes embryonic lethality, and
      microscopy analysis of the aborted embryos revealed developmental arrest after
      the heart stage, with no defect being found in the pollen. CEK4 is preferentially
      expressed in the vasculature, organ boundaries, and mature embryos, and CEK4 was
      mainly localized to the plasma membrane. Overexpression of CEK4 in wild-type
      Arabidopsis increased the levels of PtdCho in seedlings and mature siliques and
      of major membrane lipids in seedlings and triacylglycerol in mature siliques.
      CEK4 may be the plasma membrane-localized isoform of the CEK family involved in
      the rate-limiting step of PtdCho biosynthesis and appears to be required for
      embryo development in Arabidopsis. 

PMID- 25966763
TI  - Two N-terminal acetyltransferases antagonistically regulate the stability of a
      nod-like receptor in Arabidopsis.
AB  - Nod-like receptors (NLRs) serve as immune receptors in plants and animals. The
      stability of NLRs is tightly regulated, though its mechanism is not well
      understood. Here, we show the crucial impact of N-terminal acetylation on the
      turnover of one plant NLR, Suppressor of NPR1, Constitutive 1 (SNC1), in
      Arabidopsis thaliana. Genetic and biochemical analyses of SNC1 uncovered its
      multilayered regulation by different N-terminal acetyltransferase (Nat)
      complexes. SNC1 exhibits a few distinct N-terminal isoforms generated through
      alternative initiation and N-terminal acetylation. Its first Met is acetylated by
      N-terminal acetyltransferase complex A (NatA), while the second Met is acetylated
      by N-terminal acetyltransferase complex B (NatB). Unexpectedly, the NatA-mediated
      acetylation serves as a degradation signal, while NatB-mediated acetylation
      stabilizes the NLR protein, thus revealing antagonistic N-terminal acetylation of
      a single protein substrate. Moreover, NatA also contributes to the turnover of
      another NLR, RESISTANCE TO P. syringae pv maculicola 1. The intricate regulation
      of protein stability by Nats is speculated to provide flexibility for the target
      protein in maintaining its homeostasis. 

PMID- 25966767
TI  - Do Leukaemia Inhibitory Factor and Vascular Endothelial Growth Factor Have Any
      Roles in Intrauterine Device Mechanism of Action? An Experimental Rat Study.
AB  - OBJECTIVE: To assess leukaemia inhibitory factor (LIF) and vascular endothelial
      growth factor (VEGF) expression as markers of intrauterine device (IUD) efficacy
      in a rat model. METHODS: Twenty nulliparous female Wistar rats were divided into
      two groups with 10 animals per group: group I (IUD) and group II (control group,
      no IUD). In group I, a 2-cm 3-0 silk suture was placed into one horn of the rat
      bicornuate uterus. On day 20 (after IUD insertion) rats were sacrificed and their
      uteri removed. The number of vessels and the distribution of LIF and VEGF were
      compared among the uterine horns. RESULTS: There were no significant differences
      in LIF and VEGF expression in the groups and all horns (p > 0.05). The number of
      vessels was higher in the IUD+ horn than in the IUD- horn of group I and in the
      horn of group II (p < 0.05). There was no significant difference in the number of
      vessels between the IUD- horns of groups I and II (p > 0.05). CONCLUSION: LIF and
      VEGF expression did not correlate with IUD efficacy in a rat model. An IUD may
      increase the number of vessels in the uterine horn independent of VEGF
      expression. (c) 2015 S. Karger AG, Basel.

PMID- 25966766
TI  - Renalase protects the cardiomyocytes of Sprague-Dawley rats against ischemia and
      reperfusion injury by reducing myocardial cell necrosis and apoptosis.
AB  - BACKGROUND/AIMS: Renalase, a novel flavoprotein expressed in the kidney and
      heart, reduces renal tubular necrosis and apoptosis, which suggests that it might
      protect against necrosis and/or apoptosis in myocardial ischemia reperfusion
      injury (MIRI). The present study thus explored the effects of renalase on Sprague
      Dawley (SD) rats subjected to MIRI. METHODS: We used Lentivirus-mediated RNA
      interference (RNAi) to inhibit the renalase gene expression in the heart tissue
      via pericardial cavity injection. The MIRI animal modal was established by
      blocking the left anterior descending artery for 45mins followed by 4h of
      reperfusion. Real-time PCR and western blotting were used to detect renalase
      expression in the heart tissue. Double staining and TUNEL were used to detect the
      necrosis and apoptosis in the myocardial cells, respectively. RESULTS: All rats
      subjected to MIRI exhibited lower levels of renalase in the heart tissue than did
      the sham-operated group (P<0.05, n=6). The (RNAi) group rats exhibited lower
      renalase levels than did the controls and also exhibited more serious necrosis
      (7.12+/-0.56% vs. 3.32+/-0.93%, P<0.05, n=6) and apoptosis (151.8+/-8.2% vs.
      66.8+/-6.5%, P<0.05, n=6); however, pretreatment with the recombinant renalase
      significantly reduced myocardial cell necrosis (1.51+/-0.12% vs. 4.13+/-0.02%,
      P<0.05, n=6) and apoptosis (21.3+/-5.0% vs. 52.6+/-10.4%, P<0.05, n=6) relative
      to the control rats. CONCLUSIONS: Exogenous recombinant renalase protein reduced
      myocardial cell necrosis and apoptosis. Recombinant renalase protein might be a
      new cardiovascular drug for ischemia/IR injury.

PMID- 25966768
TI  - What cancer patients find in the internet: the visibility of evidence-based
      patient information - analysis of information on German websites.
AB  - BACKGROUND: The internet is an easy and always accessible source of information
      for cancer patients. The aim of our study was to evaluate the information
      provided on German websites. MATERIAL AND METHODS: We developed an instrument
      based on criteria for patient information from the German Network for Evidence
      based Medicine, the Agency for Quality in Medicine, HONcode, DISCERN, and the
      afgis. We simulated a patient's search and derived the websites for evaluation.
      We analyzed the visibility of each website and evaluated the websites using the
      developed instrument. RESULTS: We analyzed 77 websites. The highest visibility
      index was shown by 4 profit websites. Websites from professional societies and
      self-help groups have low rankings. Concerning quality, websites from non-profit
      providers and self-help groups are on top. Websites with a profit interest have
      the lowest average score. CONCLUSIONS: A discrepancy exists between the
      visibility and the quality of the analyzed websites. With the internet becoming
      an important source of information on cancer treatments for patients, this may
      lead to false information and wrong decisions. We provide a list of suggestions
      as to how this risk may be reduced by complementary information from the
      physician and from trustworthy websites.

PMID- 25966769
TI  - NADIR: A Non-Interventional Study on the Prophylaxis of Chemotherapy-Induced
      Neutropenia Using Lipegfilgrastim - First Interim Analysis.
AB  - BACKGROUND: The non-interventional study (NIS) NADIR was designed to assess the
      effectiveness and safety of lipegfilgrastim, a novel glycopegylated granulocyte
      colony stimulating factor, in reducing the risk of both febrile and severe
      neutropenia. METHODS: Here, the interim analysis of NIS Nadir performed under
      real-world conditions at 80 oncology practices across Germany is reported. For a
      patient to be included, lipegfilgrastim at a subcutaneous single dose of 6 mg had
      to be administered during at least 1 cycle of the chemotherapy under
      consideration. RESULTS: The interim analysis included 224 patients. Median
      patient age was 61.1 years (interquartile range 51.2-70.2 years). Main tumor type
      was breast cancer followed by lung cancer, and non-Hodgkin's lymphoma (46.0,
      13.4, and 10.7%, respectively). When lipegfilgrastim was given as primary
      prophylaxis, no patient developed febrile neutropenia (FN). 1.3% of patients
      developed FN when primary prophylaxis was withheld. Only 68.6% of patients
      undergoing chemotherapy and at high risk (> 20%) of developing FN were treated
      with lipegfilgrastim during the first cycle, exposing disparity between real
      world practices and current treatment guidelines. Lipegfilgrastim was well
      tolerated. The only grade 3/4 treatment-related adverse event was anemia in 1
      patient. CONCLUSION: Lipegfilgrastim was effective and safe when administered for
      the prevention of chemotherapy-induced neutropenia under real-world conditions.

PMID- 25966770
TI  - Does physical activity improve quality of life in cancer patients undergoing
      chemotherapy?
AB  - BACKGROUND: Improved cancer treatments have resulted in prolonged survival.
      Nevertheless, tumor symptoms and side effects still compromise physical activity
      and quality of life (QoL). PATIENTS AND METHODS: We conducted an anonymous survey
      among cancer patients undergoing chemotherapy using standardized questionnaires:
      the 'Freiburger Fragebogen zur korperlichen Aktivitat' (Freiburg Questionnaire on
      Physical Activity) and European Organisation for Research and Treatment of Cancer
      (EORTC) QLQ-C30. Two main questions were addressed: were there differences (1) in
      physical activity and QoL between patients who do not believe that sport could
      improve their QoL and those who believe it could (group A vs. B); and (2) in QoL
      between patients with a total activity (TA) < 18 metabolic equivalent of task
      (MET) h/week and those with a TA of >= 18 MET h/week (group C vs. D)? RESULTS:
      276 of 400 questionnaires were completed. Groups A and B were balanced in terms
      of baseline characteristics. Group A suffered significantly more from fatigue and
      pain; group B reported higher levels of global health status (GHS) and TA. Groups
      C and D differed in gender distribution, age, and educational background. Group D
      had significantly higher levels of GHS, group C suffered more from fatigue, pain,
      and appetite loss. CONCLUSION: Physical activity correlates with a better QoL of
      cancer patients undergoing chemotherapy.

PMID- 25966771
TI  - Activation of Innate Immunity in Graft-versus-Host Disease: Implications for
      Novel Targets?
AB  - Acute graft-versus-host disease (GvHD) is mediated by alloreactive donor-derived
      T cells with a suitable T cell receptor recognizing recipient major
      histocompatibility complex or minor histocompatibility antigens. However, the
      process of T cell activation and tissue injury sensing is also dependent on
      innate immune cells and non-hematopoietic cells. Different cell types of the
      innate immune system have the ability to sense danger-associated and pathogen
      associated molecular patterns via pattern recognition receptors which can be
      transmembrane Toll-like receptors or cytoplasmic nucleotide-binding
      oligomerization domain-like receptors. Infectious stimuli include bacterial,
      viral, and fungal components, while non-infectious stimuli can be components
      derived from damaged cells or extracellular matrix. A better understanding of the
      complex sensing and effector mechanisms of innate immune cells in GvHD may help
      to improve preventive and therapeutic strategies in GvHD.

PMID- 25966772
TI  - Incidental thyroid C cell hyperplasia: clinical significance and implications in
      practice.
AB  - Incidental C cell hyperplasia (CCH) following thyroidectomy for other indications
      may rarely be encountered, which may raise concerns about its clinical
      significance and proper management. CCH can be classified as physiological
      (reactive) or neoplastic. Reactive CCH has no malignant potential and can be
      observed in association with many other thyroid diseases (including
      differentiated thyroid cancer); in contrast, neoplastic CCH should be considered
      as a preneoplastic stage in the spectrum of C cell disease, ultimately leading to
      the development of medullary thyroid cancer (MTC). Neoplastic CCH is commonly
      observed in patients with germ-line mutations in the RET oncogene (commonly in
      families with a history of hereditary MTC, i.e. familial MTC or multiple
      endocrine neoplasia type 2 (MEN2)). CCH should be considered in patients with
      hypercalcitoninemia without nodular thyroidopathy. Total thyroidectomy, which is
      commonly performed for the majority of thyroid diseases, is an adequate treatment
      and achieves cure, even in patients with neoplastic CCH. There is no role for
      cervical lymph node dissection in patients with pure CCH. In conclusion, reactive
      CCH has no malignant potential, in contrast to neoplastic CCH. Total
      thyroidectomy achieves cure of patients with CCH.

PMID- 25966773
TI  - The serum CXCL13 level is associated with the Glasgow Prognostic Score in
      extranodal NK/T-cell lymphoma patients.
AB  - BACKGROUND: The Glasgow Prognostic Score (GPS) measures inflammation and proves
      its prognostic value in patients with extranodal natural killer (NK)/T-cell
      lymphoma (ENKTL) which is commonly combined with inflammatory lesion. Given
      inflammatory chemokines play an important role in tumor progression, we
      hypothesized that chemokines might influence ENKTL aggressiveness through
      interaction with their receptors in the tumor tissue. METHODS: We measured the
      serum levels of C-X-C motif ligand 13 (CXCL13) in 69 patients with ENKTL who
      received non-anthracycline-based chemotherapy and/or concurrent chemoradiotherapy
      because CXCL13 is thought to have a pro-tumor effect through interaction with its
      receptor, the C-X-C chemokine receptor 5 (CXCR5). We analyzed the association of
      serum CXCL13 with the GPS, and their prognostic relevance. The levels of CXCL13
      were measured using a multiplex chemokine assay on archived frozen serum samples.
      RESULTS: Patients were categorized into high and low CXCL13 groups if they had
      CXCL13 levels above or below the median value of 29.1 pg/mL, respectively. The
      high CXCL13 group and grouping by the GPS showed a significant association with
      poor progression-free survival. The elevated serum levels of CXCL13 were also
      significantly associated with a high score of the GPS. High CXCL13 levels and GPS
      were significantly associated with high tumor burden predicting poor prognosis
      including stages III/IV, extranasal presentation, bone marrow invasion, and
      presence of Epstein-Barr virus (EBV) DNA in blood. Furthermore, serum CXCL13 and
      GPS discriminated patients at risk of treatment failure among patients with low
      tumor burden (stage I/II) and non-detectable EBV DNA. CONCLUSIONS: Serum levels
      of CXCL13 were associated with the prognostic value of GPS. Grouping by the serum
      CXCL13 might predict survival outcomes in patients with ENKTL, suggesting that it
      is a potential therapeutic target.

PMID- 25966775
TI  - Associations between Bone Mineral Characteristics and Serum Levels of Ghrelin and
      Peptide YY in Overweight Adolescent Boys.
AB  - BACKGROUND/AIMS: The role of ghrelin and peptide YY (PYY) in bone mineralization
      is not fully known. The aim of this study was to determine whether acylated and
      des-acyl ghrelin and PYY in addition to leptin are related to bone mineral
      density (BMD) in adolescent overweight boys (OWB) and normal-weight boys (NWB).
      PARTICIPANTS AND METHODS: Fifty- five OWB (BMI >85th percentile) and 154 NWB (BMI
      <85th percentile) aged 12-16 years participated in this study. Fasting serum
      acylated and des-acyl ghrelin, PYY, leptin, testosterone levels, total body (TB)
      and lumbar spine (LS) bone mineral content (BMC), and BMD were measured. TB BMC
      for height and TB and LS bone mineral apparent density (BMAD) were calculated.
      RESULTS: No differences were seen in acylated and des-acyl ghrelin or PYY levels,
      while the leptin levels were significantly higher in the OWB compared to the NWB.
      In the OWB, TB BMAD was positively correlated with acylated ghrelin and leptin,
      and TB BMC for height was positively correlated with PYY. In the OWB, the
      variability of TB BMD was determined by TB fat-free mass and des-acyl ghrelin,
      whereas the variability of TB BMAD was determined by leptin. CONCLUSIONS: Des
      acyl ghrelin and PYY are involved in the bone mineralization process in puberty,
      and the impact can vary between normal and overweight subjects.

PMID- 25966777
TI  - MMP13 Regulates Aggressiveness of Pediatric Multiple Myeloma Through VEGF-C.
AB  - BACKGROUND/AIMS: Even though the blood and lymphatic vascular systems are both
      involved in the occurrence of cancer metastases, it is believed that lymphatic
      system is primarily responsible for the initial metastasis. Nevertheless, the
      molecular mechanisms underlying lymphangiogenesis of multiple myeloma (MM),
      especially in pediatric period, have not been clarified. METHODS: Here we studied
      vascular endothelial growth factor C (VEGF-C) and matrix metalloproteinase 13
      (MMP13) in pediatric MM patients. We overexpressed or inhibited VEGF-C in MM
      cells to study their effects on MMP13, and vice versa. A specific inhibitor for
      PI3k/Akt signaling pathway was used to examine the role of PI3k/Akt signaling in
      this regulatory axis. RESULTS: Both VEGF-C and MMP13 significantly upregulated in
      MM with lymph-node metastases. A strong correlation between VEGF-C and MMP13 were
      detected in MM specimen. Using a human MM line 8226, we found that VEGF-C was
      regulated by MMP13 in MM cells, but not vice versa. Moreover, a specific PI3k/Akt
      inhibitor significantly abolished the effect of MMP13 on VEGF-C activation.
      CONCLUSION: Since VEGF-C is a well-known growth factor for lymphatic vessels, our
      data suggest that MMP13 may activate VEGF-C to promote cancer cell metastasis
      through lymphatic vascular systems in pediatric MM.

PMID- 25966776
TI  - Exploring the association between parental rearing styles and medical students'
      critical thinking disposition in China.
AB  - BACKGROUND: Critical thinking is an essential ability for medical students.
      However, the relationship between parental rearing styles and medical students'
      critical thinking disposition has rarely been considered. The aim of this study
      was to investigate whether parental rearing styles were significant predictors of
      critical thinking disposition among Chinese medical students. METHODS: 1,075
      medical students from the first year to the fifth year attending one of three
      medical schools in China were recruited via multistage stratified cluster
      sampling. The Chinese Critical Thinking Disposition Inventory(CTDI-CV) and The
      Egna Minnen av Barndoms Uppfostran (EMBU) questionnaire were applied to collect
      data and to conduct descriptive analysis. Stepwise multiple linear regression was
      used to analyze the data. RESULTS: The critical thinking disposition average mean
      score was 287.44 with 632 participants (58.79%) demonstrating positive critical
      thinking disposition. Stepwise multiple linear regression analysis revealed that
      the rearing styles of fathers, including "overprotection", "emotional warmth and
      understanding", "rejection" and "over-interference" were significant predictors
      of medical students' critical thinking disposition that explained 79.0% of the
      variance in critical thinking ability. Rearing styles of mothers including
      "emotional warmth and understanding", "punishing" and "rejection" were also found
      to be significant predictors, and explained 77.0% of the variance. CONCLUSIONS:
      Meaningful association has been evidenced between parental rearing styles and
      Chinese medical students' critical thinking disposition. Parental rearing styles
      should be considered as one of the many potential determinant factors that
      contribute to the cultivation of medical students' critical thinking capability.
      Positive parental rearing styles should be encouraged in the cultivation of
      children's critical thinking skills.

PMID- 25966779
TI  - Sustainable synthesis of a catalytic active one-dimensional lanthanide-organic
      coordination polymer.
AB  - Rationalization of the synthetic conditions allowed the predictable fast
      sustainable preparation of [La2(H3nmp)2(H2O)4].4.5H2O having a 1D coordination
      polymer. The material exhibits a remarkable chemical stability, can be converted
      into other layered compounds, and is an excellent catalyst surpassing other
      related materials. 

PMID- 25966778
TI  - Dendritic Cells Transfected with a DNA Construct Encoding Tumour-associated
      Antigen Epitopes Induce a Cytotoxic Immune Response Against Autologous Tumour
      Cells in a Culture of Mononuclear Cells from Colorectal Cancer Patients.
AB  - Significant effort has been devoted to developing effective cancer vaccines based
      on dendritic cells (DCs) loaded with various tumour antigens, including DNA
      constructs that carry sequences of tumour-associated antigens (TAAs). Such
      vaccines efficiently and selectively activate the T cell immune response. In this
      study, we describe a method to induce an antitumour immune response in
      mononuclear cell (MNC) cultures from colorectal cancer patients using DNA
      transfected DCs encoding TAA epitopes of carcinoembryonic antigen, epithelial
      cell adhesion molecule and mucin 4. DCs were obtained from peripheral blood
      monocytes of colorectal cancer patients. Magnetic-assisted transfection was used
      to deliver the genetic constructs to DCs. To assess the potency of the immune
      response, the antitumour cytotoxic response was assessed by lymphocyte
      intracellular perforin and the MNC cytotoxic activity against autologous tumour
      cells. We showed that polyepitope DNA-transfected DCs enhanced MNC antitumour
      activity, increasing tumour cell death and the percentage of perforin-positive
      lymphocytes. In addition, DNA-transfected DCs elicited a cytotoxic response that
      was as efficient as that of tumour lysate-loaded DCs. Taken together, the data
      suggest that it is feasible to induce an antitumour immune response in colorectal
      MNCs using transfected DCs. Thus, the DNA construct reported in this study may
      potentially be used in therapeutic and prophylactic DC-based vaccines. 

PMID- 25966780
TI  - Direct observation of breaking of the intramolecular H-bond, and slowing down of
      the proton motion and tuning its mechanism in an HBO derivative.
AB  - We report on spectroscopic and photodynamical behaviours of 5-amino-2-(2'
      hydroxyphenyl)benzoxazole (5A-HBO) in different solutions. The dye undergoes an
      ultrafast ICT reaction (<50 fs) (comparable to that observed for its methylated
      derivative, 5A-MBO), in agreement with the results of TD-DFT theoretical
      calculations (gas phase). Depending on the used solvent, the ICT reaction can be
      followed by a reversible/irreversible excited-state intramolecular proton
      transfer (ESIPT) reaction or by breaking of the intramolecular hydrogen bond
      (IHB). 5A-HBO in n-heptane solution exhibits an irreversible and slow (20 ps)
      ESIPT reaction, while that of the parent compound, HBO, takes place in less than
      150 fs. Compared to excited HBO behaviour, theoretical calculations on 5A-HBO
      suggest a higher energy barrier (~4 kcal mol(-1)) between the relaxed enol and
      keto tautomers, in addition to a less stabilization of the latter, which is in
      agreement with experiments in n-heptane. On the other hand, in dichloromethane,
      after the ICT reaction a subsequent and reversible proton motion occurs in an
      extraordinary slower regime (ns-time scale). No isotopic effect (OH/OD exchange)
      was observed in this solvent reflecting that the reversible ESIPT reaction
      evolves along the IHB and solvent coordinates. Using tetrahydrofurane and
      acetonitrile, we observed a breaking of the IHB due to specific intermolecular
      interactions with solvent molecules. This leads to the formation of open-enol
      forms, which undergo an ICT reaction as it occurs in 5A-MBO. These results bring
      new findings in the coupled ICT and ESIPT reactions. The photobehaviour of this
      new dye remarkably changes with the solvent nature, opening up the window for
      further research and possible applications in sensing polarity or H-bonding of
      media similar to that of the biological ones. 

PMID- 25966781
TI  - Evaluation of the QT effect of a combination of piperaquine and a novel anti
      malarial drug candidate OZ439, for the treatment of uncomplicated malaria.
AB  - AIMS: The aim was to investigate the QT effect of a single dose combination
      regimen of piperaquine phosphate (PQP) and a novel aromatic trioxolane, OZ439,
      for malaria treatment. METHODS: Exposure-response (ER) analysis was performed on
      data from a placebo-controlled, single dose, study with OZ439 and PQP. Fifty-nine
      healthy subjects aged 18 to 55 years received OZ439 alone or placebo in a first
      period, followed by OZ439 plus PQP or matching placebos in period 2. OZ439 and
      PQP doses ranged from 100-800 mg and 160-1440 mg, respectively. Twelve-lead ECG
      tracings and PK samples were collected serially pre- and post-dosing. RESULTS: A
      significant relation between plasma concentrations and placebo-corrected change
      from baseline QTc F (DeltaDeltaQTc F) was demonstrated for piperaquine, but not
      for OZ439, with a mean slope of 0.047 ms per ng ml(-1) (90% CI 0.038, 0.057).
      Using an ER model that accounts for plasma concentrations of both piperaquine and
      OZ439, a largest mean QTc F effect of 14 ms (90% CI 10, 18 ms) and 18 ms (90% CI
      14, 22 ms) was predicted at expected plasma concentrations of a single dose 800
      mg OZ439 combined with PQP 960 mg (188 ng ml(-1) ) and 1440 mg (281 ng ml(-1) ),
      respectively, administered in the fasted state. CONCLUSIONS: Piperaquine prolongs
      the QTc interval in a concentration-dependent way. A single dose regimen
      combining 800 mg OZ439 with 960 mg or 1440 mg PQP is expected to result in lower
      peak piperaquine plasma concentrations compared with available 3 day PQP
      artemisinin combinations and can therefore be predicted to cause less QTc
      prolongation.

PMID- 25966782
TI  - Socioeconomic inequality and mortality--a regional Danish cohort study.
AB  - BACKGROUND: Socioeconomic inequalities in mortality pose a serious impediment to
      enhance public health even in highly developed welfare states. This study aimed
      to improve the understanding of socioeconomic disparities in all-cause mortality
      by using a comprehensive approach including a range of behavioural,
      psychological, material and social determinants in the analysis. METHODS: Data
      from The North Denmark Region Health Survey 2007 among residents in Northern
      Jutland, Denmark, were linked with data from nationwide administrative registries
      to obtain information on death in a 5.8-year follow-up period (1(st) February
      2007- 31(st) December 2012). Socioeconomic position was assessed using
      educational status as a proxy. The study population was assigned to one of five
      groups according to highest achieved educational level. The sample size was 8,837
      after participants with missing values or aged below 30 years were excluded. Cox
      regression models were used to assess the risk of death from all causes according
      to educational level, with a step-wise inclusion of explanatory covariates.
      RESULTS: Participants' mean age at baseline was 54.1 years (SD 12.6); 3,999 were
      men (45.3%). In the follow-up period, 395 died (4.5%). With adjustment for age
      and gender, the risk of all-cause mortality was significantly higher in the two
      least-educated levels (HR = 1.5, 95%, CI = 1.2-1.8 and HR = 3.7, 95% CI = 2.4
      5.9, respectively) compared to the middle educational level. After adjustment for
      the effect of subjective and objective health, similar results were obtained (HR
      = 1.4, 95% CI = 1.1-1.7 and HR = 3.5, 95% CI = 2.0-6.3, respectively). Further
      adjustment for the effect of behavioural, psychological, material and social
      determinants also failed to eliminate inequalities found among groups, the risk
      remaining significantly higher for the least educated levels (HR = 1.4, 95% CI =
      1.1-1.9 and HR = 4.0, 95% CI = 2.3-6.8, respectively). In comparison with the
      middle level, the two highest educated levels remained statistically
      insignificant throughout the entire analysis. CONCLUSION: Socioeconomic
      inequality influenced mortality substantially even when adjusted for a range of
      determinants that might explain the association. Further studies are needed to
      understand this important relationship.

PMID- 25966784
TI  - Efficient inorganic solid solar cells composed of perovskite and PbS quantum
      dots.
AB  - Lead halide perovskite solar cells have attracted great interest due to their
      high efficiency and simple fabrication process. However, the high efficiency
      heavily relies on expensive organic hole-transporting materials (OHTMs) such as
      2,2',7,7'-tetrakis(N,N-di-p-methoxyphenylamine)-9,9'-spirobifluorene (spiro
      MeOTAD), it is preferable to replace these expensive OHTMs by inorganic and low
      cost materials. Here, we report colloidal PbS quantum dots synthesized by a
      facile method and used as the inorganic hole-transporting material in a hybrid
      perovskite solar cell. By controlling the crystalline morphology of the
      perovskite capping layer, the recombination process is significantly retarded.
      Furthermore, a pure inorganic solar cell prepared by a two-step process
      demonstrated a nearly 8% power conversion efficiency due to efficient charge
      separation by a cascade of junctions and retarding charge recombination by a void
      free capping layer. The stability of the inorganic solar cell was also tested
      with a little decay observed within ca. 100 h. 

PMID- 25966783
TI  - A RIG-I 2CARD-MAVS200 Chimeric Protein Reconstitutes IFN-beta Induction and
      Antiviral Response in Models Deficient in Type I IFN Response.
AB  - RIG-I-like receptors (RLRs) are cellular sensor proteins that detect certain RNA
      species produced during viral infections. RLRs activate a signaling cascade that
      results in the production of IFN-beta as well as several other cytokines with
      antiviral and proinflammatory activities. We explored the potential of different
      constructs based on RLRs to induce the IFN-beta pathway and create an antiviral
      state in type I IFN-unresponsive models. A chimeric construct composed of RIG-I
      2CARD and the first 200 amino acids of MAVS (2CARD-MAVS200) showed an enhanced
      ability to induce IFN-beta when compared to other stimulatory constructs.
      Furthermore, this human chimeric construct showed a superior ability to activate
      IFN-beta expression in cells from various species. This construct was found to
      overcome the restrictions of blocking IFN-beta induction or signaling by a number
      of viral IFN-antagonist proteins. Additionally, the antiviral activity of this
      chimera was demonstrated in influenza virus and HBV infection mouse models using
      adeno-associated virus (AAV) vectors as a delivery vehicle. We propose that AAV
      vectors expressing 2CARD-MAVS200 chimeric protein can reconstitute IFN-beta
      induction and recover a partial antiviral state in different models that do not
      respond to recombinant IFN-beta treatment. 

PMID- 25966785
TI  - A rare manifestation of renal osteodystrophy in a non-compliant hemodialysis
      child: Questions.

PMID- 25966786
TI  - A rare manifestation of renal osteodystrophy in a non-compliant child on
      hemodialysis: Answers.

PMID- 25966787
TI  - Peptide aptamers: The versatile role of specific protein function inhibitors in
      plant biotechnology.
AB  - In recent years, peptide aptamers have emerged as novel molecular tools that have
      attracted the attention of researchers in various fields of basic and applied
      science, ranging from medicine to analytical chemistry. These artificial short
      peptides are able to specifically bind, track, and inhibit a given target
      molecule with high affinity, even molecules with poor immunogenicity or high
      toxicity, and represent a remarkable alternative to antibodies in many different
      applications. Their use is on the rise, driven mainly by the medical and
      pharmaceutical sector. Here we discuss the enormous potential of peptide aptamers
      in both basic and applied aspects of plant biotechnology and food safety. The
      different peptide aptamer selection methods available both in vivo and in vitro
      are introduced, and the most important possible applications in plant
      biotechnology are illustrated. In particular, we discuss the generation of broad
      based virus resistance in crops, "reverse genetics" and aptasensors in bioassays
      for detecting contaminations in food and feed. Furthermore, we suggest an
      alternative to the transfer of peptide aptamers into plant cells via genetic
      transformation, based on the use of cell-penetrating peptides that overcome the
      limits imposed by both crop transformation and Genetically Modified Organism
      commercialization.

PMID- 25966789
TI  - Emodin is identified as the active component of ether extracts from Rhizoma
      Polygoni Cuspidati, for anti-MRSA activity.
AB  - This study investigated the anti-methicillin-resistant Staphylococcus aureus
      (anti-MRSA) activity and chemical compositions of ether extracts from Rhizoma
      Polygoni Cuspidati (ET-RPC). Significant anti-MRSA activities of ET-RPC against
      MRSA252 and MRSA clinical strains were tested in in vitro antibacterial
      experiments, such as inhibition zone diameter test, minimal inhibitory
      concentration test, and dynamic bacterial growth assay. Subsequently, 7 major
      compounds of ET-RPC were purified and identified as polydatin, resveratrol-4-O-d
      (6'-galloyl)-glucopyranoside, resveratrol, torachryson-8-O-glucoside, emodin-8-O
      glucoside, 6-hydroxy-emodin, and emodin using liquid chromatography -
      electrospray ionization - tandem mass spectrometry. After investigation of anti
      MRSA activities of the 7 major compounds, only emodin had significant anti-MRSA
      activity. Further, transmission electron microscopy was used to observe
      morphological changes in the cell wall of MRSA252, and the result revealed that
      emodin could damage the integrity of cell wall, leading to loss of intracellular
      components. In summary, our results showed ET-RPC could significantly inhibit
      bacterial growth of MRSA strains. Emodin was identified as the major compound
      with anti-MRSA activity; this activity was related to destruction of the
      integrity of the cell wall and cell membrane. 

PMID- 25966790
TI  - A Novel Composite PMMA-based Bone Cement with Reduced Potential for Thermal
      Necrosis.
AB  - Percutaneous vertebroplasty (VP) and balloon kyphoplasty (BKP) are now widely
      used to treat patients who suffer painful vertebral compression fractures. In
      each of these treatments, a bone cement paste is injected into the fractured
      vertebral body/bodies, and the cement of choice is a poly(methyl methacrylate)
      (PMMA) bone cement. One drawback of this cement is the very high exothermic
      temperature, which, it has been suggested, causes thermal necrosis of surrounding
      tissue. In the present work, we prepared novel composite PMMA bone cement where
      microcapsules containing a phase change material (paraffin) (PCMc) were mixed
      with the powder of the cement. A PCM absorbs generated heat and, as such, its
      presence in the cement may lead to reduction in thermal necrosis. We determined a
      number of properties of the composite cement. Compared to the values for a
      control cement (a commercially available PMMA cement used in VP and BKP), each
      composite cement was found to have significantly lower maximum exothermic
      temperature, increased setting time, significantly lower compressive strength,
      significantly lower compressive modulus, comparable biocompatibility, and
      significantly smaller thermal necrosis zone. Composite cement containing 20% PCMc
      may be suitable for use in VP and BKP and thus deserves further evaluation. 

PMID- 25966791
TI  - Phase II dose-finding study of balugrastim in breast cancer patients receiving
      myelosuppressive chemotherapy.
AB  - Balugrastim is a once-per-cycle, fixed-dose recombinant protein comprising human
      serum albumin and granulocyte colony-stimulating factor under development for
      prevention of severe neutropenia in cancer patients receiving myelosuppressive
      chemotherapy. This phase II, multicenter, active-controlled, dose-finding pilot
      study evaluated balugrastim safety and efficacy versus pegfilgrastim in breast
      cancer patients scheduled to receive myelosuppressive chemotherapy and
      investigated two doses with similar efficacy to pegfilgrastim for a subsequent
      phase III study. Patients received four cycles of doxorubicin/docetaxel
      chemotherapy and with each successive cycle were randomized sequentially to
      escalating doses of balugrastim [30 (n = 11), 40 (n = 21), or 50 mg (n = 20)] or
      a fixed dose of pegfilgrastim [6 mg (n = 26)] post-chemotherapy. Balugrastim
      doses were escalated as planned. The incidence of adverse events was similar
      among the balugrastim groups and between all balugrastim doses and pegfilgrastim.
      The most frequently reported adverse events were neutropenia, alopecia, and
      nausea. During cycle 1, severe neutropenia (absolute neutrophil count of <0.5 *
      10(9)/L) occurred in 40, 67, and 50 % and febrile neutropenia occurred in 20.0,
      9.5, and 10.0 % of patients receiving balugrastim 30, 40, and 50 mg,
      respectively; in patients receiving pegfilgrastim, 48 % experienced severe
      neutropenia and 8 % experienced febrile neutropenia. Duration of severe
      neutropenia (DSN) for each treatment group was 0.9, 1.6, 1.1, and 0.9 days,
      respectively. In the remaining three chemotherapy cycles, DSN was <=1 day across
      all treatment groups. Balugrastim 50 mg was comparable to pegfilgrastim in terms
      of safety and overall efficacy in breast cancer patients receiving
      myelosuppressive chemotherapy.

PMID- 25966793
TI  - M-mode colour Doppler: where art meets science.

PMID- 25966792
TI  - Efficacy and tolerability of crizotinib in the treatment of ALK-positive,
      advanced non-small cell lung cancer in Chinese patients.
AB  - Crizotinib has been reported to be particularly effective and to have acceptable
      toxicity in advanced anaplastic lymphoma kinase (ALK)-positive, non-small cell
      lung cancer (NSCLC). In this study, we analyzed the efficacy and tolerability of
      crizotinib in the treatment of 72 Chinese patients with ALK-positive, advanced
      NSCLC. All patients received oral crizotinib 250 mg twice daily in 28-day cycles
      during the period June 1, 2013, to October 15, 2014. The tumor response was
      assessed after the first cycle of crizotinib and then after every two cycles
      using the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0.
      Tolerability was assessed at least twice per cycle until crizotinib was
      discontinued. The patients tended to be young (mean age 55 years, range 31-83
      years), never or light smokers (smoking index <400), and to have an
      adenocarcinoma histology. Most (49/72; 68.1 %) had received previous anticancer
      treatment before crizotinib therapy. Sixty-seven patients (93 %) were able to be
      assessed for efficacy. The objective response rate and disease control rate were
      52.2 % (95 % CI 40.5-63.9 %) and 64.2 % (95 % CI 52.75-75.7 %), respectively. The
      estimated median progression-free survival for all 67 patients was 10.3 months
      (95 % CI 8.6-12.0 months). Mild visual disturbances, nausea, vomiting, diarrhea
      and constipation were the most commonly reported adverse effects. Thus,
      crizotinib was well tolerated and showed promising efficacy in Chinese patients
      with ALK-positive, advanced NSCLC. Further prospective, multicenter studies with
      a larger sample size are needed to confirm these findings.

PMID- 25966794
TI  - [Ultrasonographic examination of the stifle joint in the dog. Part 2: Impaired
      wound healing and neoplastic, congenital, developmental, degenerative and
      traumatic disorders].
AB  - Ultrasonography is a cost-effective, non-invasive technique, which can be
      performed in conscious dogs. It frequently contributes valuable and even crucial
      diagnostic information in patients with lameness attributed to the stifle joint.
      Within the first part of this article, technical requirements and limitations as
      well as the standardized scanning protocol and ultrasonographic anatomy of the
      stifle joint are described. Additionally, ultrasonographic features of common
      pathologies of the stifle joint, including cranial cruciate ligament rupture and
      meniscal pathologies, are discussed. The second part of the article focuses on
      the ultrasonographic approach to other, less common pathologies of the canine
      stifle joint, including impaired wound healing and congenital, neoplastic,
      developmental and traumatic disorders. 

PMID- 25966795
TI  - Interaction of Alcanivorax borkumensis with a Surfactant Decorated Oil-Water
      Interface.
AB  - Alcanivorax borkumensis is a hydrocarbon degrading bacterium linked to oil
      degradation around oil spill sites. It is known to be a surface bacterium leading
      to substantial interaction with the oil-water interface. Because of its abundance
      in oil spill regions, it has great potential to be used actively in oil spill
      remediation. Dispersants are thought to be important in the creation of oil-in
      water emulsions that are meant to aid in the biodegradation process by bacteria.
      Although it is likely that some sort of dispersant will be used again in the case
      of another oil spill, to date, no studies have shown the impact of dispersants on
      the bacteria population. Corexit 9500 was the main dispersant used during the
      Deepwater Horizon oil spill, but little is known about its effect on the bacteria
      community. We built an experimental platform to quantitatively measure the
      transient growth of Alcanivorax borkumensis at the interface of oil and water. To
      our knowledge, this is the first study of how A. borkumensis interacts with a
      surfactant decorated oil-water interface. We use COREXIT EC9500A,
      cetylytrimethylamonium bromide, dioctyl sulfosuccinate sodium salt, l-alpha
      phosphatidylcholine, sodium dodecyl sulfate, and Tween 20 to investigate the
      impact of dispersants on Alcanivorax borkumensis. We assess the impact of these
      dispersants on the growth rate, lag time, and maximum concentration of
      Alcanivorax borkumensis. We show that the charge, structure, and surface activity
      of these surfactants greatly impact the growth of A. borkumensis. Our results
      indicated that out of the surfactants tested only Tween 20 assists Acanivorax
      borkumensis growth. The results of this study will be important in the decision
      of dispersant use in the future. 

PMID- 25966797
TI  - Brooding strategy in fluctuating salinity environments: oxygen availability in
      the pallial cavity and metabolic stress in females and offspring in the Chilean
      oyster Ostrea chilensis.
AB  - Organisms that encounter stressful situations in nature often cope using
      behavioral (e.g., avoidance) or physiological tactics. In sessile mollusks, the
      only available behavioral option in dealing with salinity stress is to "clam up",
      isolating their tissues from the environment. Though effective in the short term,
      prolonged isolation can have detrimental physiological consequences, particularly
      for females brooding embryos in a mantle cavity that is isolated from the
      external environment. In the Quempillen estuary, the Chilean oyster, Ostrea
      chilensis, spent nearly one-third of its brooding season at salinities low enough
      to cause female isolation. When females thus isolated themselves, the dissolved
      oxygen in their mantle cavity fluid dropped to hypoxic levels within 10 min. In
      females that were brooding embryos, this depletion of oxygen was not uniform:
      oxygen was depleted more quickly in the palp region (where embryos accumulate)
      than in the inhalant region. Additionally, oxygen was reduced even more quickly
      in the palp region when females were brooding late-stage embryos, which consumed
      oxygen significantly more quickly than embryos in earlier developmental stages.
      Finally, O. chilensis used anaerobic metabolism to cope with the hypoxia induced
      by isolation, as lactate accumulated in the tissues of both females (brooding >
      non-brooding) and embryos (late stage > early stage). Our findings demonstrate
      the trade-off between an adaptive avoidance behavior (clamming up) and the
      potentially detrimental consequences brought on by such a behavior (hypoxia).
      Cycling of embryos throughout the mantle cavity by deliberate female pumping
      keeps them from accumulating in the area between the palps, forestalling the
      creation of hypoxic conditions there. In addition, the capacity for anaerobic
      metabolism by both females and their embryos should help them tolerate the low
      oxygen levels that do eventually arise when the pallial cavity is isolated from
      the surrounding environment during long periods of reduced ambient salinity.

PMID- 25966796
TI  - Brown adipose tissue: physiological function and evolutionary significance.
AB  - In modern eutherian (placental) mammals, brown adipose tissue (BAT) evolved as a
      specialized thermogenic organ that is responsible for adaptive non-shivering
      thermogenesis (NST). For NST, energy metabolism of BAT mitochondria is increased
      by activation of uncoupling protein 1 (UCP1), which dissipates the proton motive
      force as heat. Despite the presence of UCP1 orthologues prior to the divergence
      of teleost fish and mammalian lineages, UCP1's significance for thermogenic
      adipose tissue emerged at later evolutionary stages. Recent studies on the
      presence of BAT in metatherians (marsupials) and eutherians of the afrotherian
      clade provide novel insights into the evolution of adaptive NST in mammals. In
      particular studies on the 'protoendothermic' lesser hedgehog tenrec (Afrotheria)
      suggest an evolutionary scenario linking BAT to the onset of eutherian
      endothermy. Here, we review the physiological function and distribution of BAT in
      an evolutionary context by focusing on the latest research on phylogenetically
      distinct species. 

PMID- 25966798
TI  - Insights into the Anaerobic Biodegradation Pathway of n-Alkanes in Oil Reservoirs
      by Detection of Signature Metabolites.
AB  - Anaerobic degradation of alkanes in hydrocarbon-rich environments has been
      documented and different degradation strategies proposed, of which the most
      encountered one is fumarate addition mechanism, generating alkylsuccinates as
      specific biomarkers. However, little is known about the mechanisms of anaerobic
      degradation of alkanes in oil reservoirs, due to low concentrations of signature
      metabolites and lack of mass spectral characteristics to allow identification. In
      this work, we used a multidisciplinary approach combining metabolite profiling
      and selective gene assays to establish the biodegradation mechanism of alkanes in
      oil reservoirs. A total of twelve production fluids from three different oil
      reservoirs were collected and treated with alkali; organic acids were extracted,
      derivatized with ethanol to form ethyl esters and determined using GC-MS
      analysis. Collectively, signature metabolite alkylsuccinates of parent compounds
      from C1 to C8 together with their (putative) downstream metabolites were detected
      from these samples. Additionally, metabolites indicative of the anaerobic
      degradation of mono- and poly-aromatic hydrocarbons (2-benzylsuccinate,
      naphthoate, 5,6,7,8-tetrahydro-naphthoate) were also observed. The detection of
      alkylsuccinates and genes encoding for alkylsuccinate synthase shows that
      anaerobic degradation of alkanes via fumarate addition occurs in oil reservoirs.
      This work provides strong evidence on the in situ anaerobic biodegradation
      mechanisms of hydrocarbons by fumarate addition. 

PMID- 25966800
TI  - Use of iliac vein tunneled cuffed catheters in elderly hemodialysis patients: a
      single-center retrospective study.
AB  - BACKGROUND: Until now, the survival of iliac vein tunneled cuffed catheters
      (TCCs) used in elderly patients has not been fully investigated. Accordingly, we
      evaluated their use in elderly hemodialysis patients with no other venous access
      options. METHODS: A total of 70 elderly patients with iliac vein TCCs undergoing
      chronic hemodialysis were included in this study. Patients' baseline
      anthropometric and laboratory parameters were measured. Incidence of catheter
      dysfunction and of catheter-related infection was documented. RESULTS: During the
      study period, a total of 99 new tunneled dialysis catheters were placed.
      Technical success rate was 100 %. Median infection-free survival and dysfunction
      free survival after catheterization was 617 and 875 catheter days, respectively.
      Mean survival time per catheter was 1067 catheter days, corresponding to a total
      observation period of 65369 catheters days. CONCLUSIONS: Iliac TCC is both
      technically feasible and effective for hemodialysis in elderly patients with no
      other venous access options.

PMID- 25966799
TI  - Best practices on pregnancy on dialysis: the Italian Study Group on Kidney and
      Pregnancy.
AB  - BACKGROUND: Pregnancy during dialysis is increasingly being reported and
      represents a debated point in Nephrology. The small number of cases available in
      the literature makes evidence-based counselling difficult, also given the
      cultural sensitivity of this issue. Hence, the need for position statements to
      highlight the state of the art and propose the unresolved issues for general
      discussion. METHODS: A systematic analysis of the literature (MESH, Emtree and
      free terms on pregnancy and dialysis) was conducted and expert opinions examined
      (Study Group on Kidney and Pregnancy; experts involved in the management of
      pregnancy in dialysis in Italy 2000-2013). Questions regarded: timing of dialysis
      start in pregnancy; mode of treatment, i.e. peritoneal dialysis (PD) versus
      haemodialysis (HD); treatment schedules (for both modes); obstetric surveillance;
      main support therapies (anaemia, calcium-phosphate parathormone; acidosis);
      counselling tips. MAIN RESULTS: Timing of dialysis start is not clear,
      considering also the different support therapies; successful pregnancy is
      possible in both PD and HD; high efficiency and strict integration with residual
      kidney function are pivotal in both treatments, the blood urea nitrogen test
      being perhaps a useful marker in this context. To date, long-hour HD has provided
      the best results. Strict, personalized obstetric surveillance is warranted;
      therapies should be aimed at avoiding vitamin B12, folate and iron deficits, and
      at correcting anaemia; vitamin D and calcium administration is safe and
      recommended. Women on dialysis should be advised that pregnancy is possible,
      albeit rare, with both types of dialysis treatment, and that a success rate of
      over 75% may be achieved. High dialysis efficiency and frequent controls are
      needed to optimize outcomes.

PMID- 25966801
TI  - Early subclinical rejection treated with low dose i.v. steroids is not associated
      to graft survival impairment: 13-years' experience at a single center.
AB  - Subclinical rejection (SCR) has been variably associated with reduced graft
      survival, development and progression of interstitial fibrosis/tubular atrophy
      and chronic allograft nephropathy, but data are controversial concerning SCR
      treatment in terms of graft survival improvement. In this single-center
      retrospective study, we enrolled 174 adult kidney transplant recipients with a
      protocol biopsy performed at 30 days after transplantation to evaluate the
      incidence rate and risk factors for early SCR and its impact on 10-year graft
      survival. Five patients showed primary non function and were excluded. Among
      159/169 (94.08 %) patients with stable graft function who underwent protocol
      biopsy, 17 (10.7 %) showed signs of SCR and were treated with low-dose
      intravenous (i.v.) steroids. Ten patients showed functional impairment, 8 (4.73
      %) resulting as acute rejection. At multivariate analysis, donor age [odds ratio
      (OR) 1.04, 95 % confidence interval (CI) 1.01-1.09], and delayed graft function
      (DGF) (OR 1.08, 95 % CI 1.03-1.12) were significantly associated with SCR. The 10
      year graft survival rate in the SCR group was similar to that in the normal
      findings group (76.5 vs. 74.9 % respectively; p = 0.61). At multivariate Cox
      regression, acute [hazard ratio (HR) 5.22, 95 % CI 1.70-16.01], but not sub
      clinical, rejection was independently associated with long-term graft failure. In
      conclusion, early protocol biopsy is a useful and safe tool to detect early SCR
      which seems not to affect the long-term survival. We suggest that this could be,
      probably, linked to early SCR treatment with low dose i.v. steroids.

PMID- 25966802
TI  - Church Attendance as a Predictor of Number of Sexual Health Topics Discussed
      Among High-Risk HIV-Negative Black Women.
AB  - Research suggests that sexual health communication is associated with safer sex
      practices. In this study, we examined the relationship between church attendance
      and sexual health topics discussed with both friends and sexual partners among a
      sample of urban Black women. Participants were 434 HIV-negative Black women who
      were at high risk for contracting HIV through heterosexual sex. They were
      recruited from Baltimore, Maryland using a network-based sampling approach. Data
      were collected through face-to-face interviews and Audio-Computer-Assisted Self
      Interviews. Fifty-four percent of the participants attended church once a month
      or more (regular attendees). Multivariate logistic regression analyses revealed
      that regular church attendance among high-risk HIV-negative Black women was a
      significant predictor of the number of sexual health topics discussed with both
      friends (AOR = 1.85, p = .003) and sexual partners (AOR = 1.68, p = .014). Future
      efforts to reduce HIV incidence among high-risk Black women may benefit from
      partnerships with churches that equip faith leaders and congregants with the
      tools to discuss sexual health topics with both their sexual partners and
      friends.

PMID- 25966803
TI  - In vitro culture of stem-like cells derived from somatic cell nuclear transfer
      bovine embryos of the Korean beef cattle species, HanWoo.
AB  - We established and maintained somatic cell nuclear transfer embryo-derived stem
      like cells (SCNT-eSLCs) from the traditional Korean beef cattle species, HanWoo
      (Bos taurus coreanae). Each SCNT blastocyst was placed individually on a feeder
      layer with culture medium containing three inhibitors of differentiation (3i).
      Primary colonies formed after 2-3 days of culture and the intact colonies were
      passaged every 5-6 days. The cells in each colony showed embryonic stem cell-like
      morphologies with a distinct boundary and were positive to alkaline phosphatase
      staining. Immunofluorescence and reverse transcription-polymerase chain reaction
      analyses also confirmed that these colonies expressed pluripotent markers. The
      colonies were maintained over 50 passages for more than 270 days. The cells
      showed normal karyotypes consisting of 60 chromosomes at Passage 50. Embryoid
      bodies were formed by suspension culture to analyse in vitro differentiation
      capability. Marker genes representing the differentiation into three germ layers
      were expressed. Typical embryonal carcinoma was generated after injecting cells
      under the testis capsule of nude mice, suggesting that the cultured cells may
      also have the potential of in vivo differentiation. In conclusion, we generated
      eSLCs from SCNT bovine embryos, using a 3i system that sustained stemness, normal
      karyotype and pluripotency, which was confirmed by in vitro and in vivo
      differentiation.

PMID- 25966804
TI  - Risk factors for pelvic organ prolapse and its recurrence: a systematic review.
AB  - INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse (POP) is a common condition
      with multifactorial etiology. The purpose of this systematic review was to
      provide an overview of literature on risk factors for POP and POP recurrence.
      METHODS: PubMed and Embase were searched with "pelvic organ prolapse" combined
      with "recurrence" and combined with "risk factors," with Medical Subject Headings
      and Thesaurus terms and text words variations until 4 August 2014, without
      language or publication date restrictions. Only cohort or cross-sectional studies
      carried out in western developed countries containing multivariate analyses and
      with a definition of POP based on anatomical references were included. POP
      recurrence had to be defined as anatomical recurrence after native tissue repair
      without mesh. Follow-up after surgery should have been at least 1 year. Articles
      were excluded if POP was not a separate entity or if it was unclear whether the
      outcome was primary POP or recurrence. RESULTS: PubMed and Embase revealed 2,988
      and 4,449 articles respectively. After preselection, 534 articles were
      independently evaluated by two researchers, of which 15 met the selection
      criteria. In 10 articles on primary POP, 30 risk factors were investigated.
      Parity, vaginal delivery, age, and body mass index (BMI) were significantly
      associated in at least two articles. In 5 articles on POP recurrence, 29 risk
      factors were investigated. Only preoperative stage was significantly associated
      in at least two articles. CONCLUSION: Parity, vaginal delivery, age, and BMI are
      risk factors for POP and preoperative stage is a risk factor for POP recurrence.

PMID- 25966805
TI  - Infragranular layers lead information flow during slow oscillations according to
      information directionality indicators.
AB  - The recurrent circuitry of the cerebral cortex generates an emergent pattern of
      activity that is organized into rhythmic periods of firing and silence referred
      to as slow oscillations (ca 1 Hz). Slow oscillations not only are dominant during
      slow wave sleep and deep anesthesia, but also can be generated by the isolated
      cortical network in vitro, being a sort of default activity of the cortical
      network. The cortex is densely and reciprocally connected with subcortical
      structures and, as a result, the slow oscillations in situ are the result of an
      interplay between cortex and thalamus. Due to this reciprocal connectivity and
      interplay, the mechanism responsible for the initiation of waves in the
      corticothalamocortical loop during slow oscillations is still a matter of debate.
      It was our objective to determine the directionality of the information flow
      between different layers of the cortex and the connected thalamus during
      spontaneous activity. With that purpose we obtained multilayer local field
      potentials from the rat visual cortex and from its connected thalamus, the
      lateral geniculate nucleus, during deep anaesthesia. We analyzed directionality
      of information flow between thalamus, cortical infragranular layers (5 and 6) and
      supragranular layers (2/3) by means of three information theoretical indicators:
      transfer entropy, symbolic transfer entropy and transcript mutual information.
      These three indicators coincided in finding that infragranular layers lead the
      information flow during slow oscillations both towards supragranular layers and
      towards the thalamus. 

PMID- 25966807
TI  - Vanishing urate, acute kidney injury episodes and a homozygous SLC2A9 mutation.

PMID- 25966806
TI  - A relationship between serum potassium concentration and insulin resistance in
      patients with type 2 diabetes mellitus.
AB  - PURPOSE: In patients with type 2 diabetes mellitus (DM), insulin-stimulated
      glucose uptake is impaired. However, the relationship between serum potassium
      concentration and insulin resistance is poorly defined. This study aimed to
      investigate the association between serum potassium concentration and insulin
      resistance in these patients. METHODS: Between April 2009 and October 2012, 180
      patients with type 2 DM were analyzed. Insulin resistance was estimated using the
      homeostasis model and assessment (HOMA) index; resistance was defined as an index
      value of >2. The association between serum potassium concentration and insulin
      resistance was analyzed using linear regression methods. The incidence of
      hyperkalemia was also evaluated during follow-up. RESULTS: Mean serum potassium
      concentration was 4.12 +/- 0.47 mEq/l. The median HOMA index score was 2.1
      (interquartile range 1.1-3.4). When the patients were compared based on insulin
      resistance, serum potassium concentration was higher in the patients with insulin
      resistance compared with the patients without (4.25 +/- 0.48 vs. 4.09 +/- 0.44
      mEq/l, p = 0.015). The variables found to be the determinants of serum potassium
      concentration included female, renal function, serum sodium level, log
      aldosterone-to-plasma renin activity ratio, glycosylated hemoglobin, and log HOMA
      index. Over a mean follow-up period of 2.6 +/- 1.1 years, 37 of 180 patients (21
      %) experienced episodic hyperkalemia. Patients with insulin resistance
      experienced episodic hyperkalemia more frequently than those without.
      CONCLUSIONS: Serum potassium concentration is likely to be increased in the
      patients with poorly controlled type 2 DM with insulin resistance than in those
      without insulin resistance.

PMID- 25966809
TI  - Robust and Powerful Affected Sibpair Test for Rare Variant Association.
AB  - Advances in DNA sequencing technology facilitate investigating the impact of rare
      variants on complex diseases. However, using a conventional case-control design,
      large samples are needed to capture enough rare variants to achieve sufficient
      power for testing the association between suspected loci and complex diseases. In
      such large samples, population stratification may easily cause spurious signals.
      One approach to overcome stratification is to use a family-based design. For rare
      variants, this strategy is especially appropriate, as power can be increased
      considerably by analyzing cases with affected relatives. We propose a novel
      framework for association testing in affected sibpairs by comparing the allele
      count of rare variants on chromosome regions shared identical by descent to the
      allele count of rare variants on nonshared chromosome regions, referred to as
      test for rare variant association with family-based internal control (TRAFIC).
      This design is generally robust to population stratification as cases and
      controls are matched within each sibpair. We evaluate the power analytically
      using general model for effect size of rare variants. For the same number of
      genotyped people, TRAFIC shows superior power over the conventional case-control
      study for variants with summed risk allele frequency f < 0.05; this power
      advantage is even more substantial when considering allelic heterogeneity. For
      complex models of gene-gene interaction, this power advantage depends on the
      direction of interaction and overall heritability. In sum, we introduce a new
      method for analyzing rare variants in affected sibpairs that is robust to
      population stratification, and provide freely available software.

PMID- 25966808
TI  - Patient profiles and outcomes following repair of irreducible and reducible
      Ventral Wall Hernias.
AB  - PURPOSE: The belief that irreducible hernias are repaired less successfully and
      with higher morbidity drives patients to seek elective repair. The aims of this
      study were threefold. First, this study sought to compare characteristics of
      patients undergoing irreducible and reducible ventral hernia repair. Second, to
      compare morbidity rates. Third, to determine which factors, including
      irreducibility, might be associated with recurrence. METHODS: This observational
      study was a retrospective review of 252 consecutive ventral hernia patients
      divided into two cohorts: 101 patients who underwent repair of an irreducible
      ventral hernia, and 152 patients underwent repair of a reducible ventral hernia.
      The mean follow-up time was approximately 4 years in both groups. RESULTS:
      Patients undergoing repair of irreducible hernias had higher median BMI (31 vs.
      27 kg/m2, p = 0.005), had their hernias longer (median 34 months compared to 12
      months, p = 0.043), had more defects on average (mean 1.8 vs. 1.4, p < 0.001),
      and were more likely to be symptomatic (83 vs. 55%, p = 0.002). Interestingly,
      neither hernia size (p = 0.821), nor the location of hernia (p = 0.261) differed
      significantly between the two groups. Morbidity rates, including rates of
      surgical site infection, obstruction, and recurrence, did not differ
      significantly; nor did recurrence-free survival (RFS) distributions. Risk factors
      for hernia recurrence on multivariate analysis included the repaired hernia being
      itself recurrent (HR = 2.06, 95% CI = 1.07-3.99, p = 0.031), the occurrence of
      post-operative surgical site infection (HR = 5.10, 95% CI = 2.18-11.91, p <
      0.001), and the occurrence of post-operative intestinal obstruction (HR = 5.18,
      95% CI = 1.82-14.75, p = 0.002). Irreducibility was not a significant predictor
      of recurrence (p = 0.152). CONCLUSION: Despite differing profiles, patients with
      these two types of hernias did not have statistically significant differences in
      morbidity. Recurrence was not observed to be associated with irreducibility but
      was found to be associated with other post-operative complications.

PMID- 25966810
TI  - [Preface].

PMID- 25966811
TI  - [Rationale, visions and limits of Immuno-oncology: Checkpoint inhibition as a new
      pillar of tumor therapy].

PMID- 25966812
TI  - [What opportunities does Immuno-oncology indicate for overarching long-term
      survival?].

PMID- 25966813
TI  - [Cancer screening-- sense or nonsense?].

PMID- 25966814
TI  - Concise Review: CXCR4/CXCL12 Signaling in Immature Hematopoiesis--Lessons From
      Pharmacological and Genetic Models.
AB  - Dominant, although nonexclusive roles of CXCR4 and its chief ligand CXCL12 in
      bone marrow (BM) retention and preservation of the relative quiescence of
      hematopoietic stem/progenitor cells (HSPCs), along with their involvement in
      human immunodeficiency virus infection, in trafficking of mature hematopoietic
      cells to sites of inflammation and in orderly migration of nonhematopoietic cells
      during embryogenesis, explain the significant interest of the scientific
      community in the mode of action of this receptor-ligand pair. In this focused
      review, we seek to distil from the large body of information that has become
      available over the years some of the key findings about the role of CXCR4/CXCL12
      in normal immature hematopoiesis. It is hoped that understanding the mechanistic
      insights gained there from will help generate hypotheses about potential avenues
      in which cancer/leukemia cell behavior can be modified by interference with this
      pathway.

PMID- 25966815
TI  - Coalition of Nuclear Receptors in the Nervous System.
AB  - A universal signaling module has been described which utilizes the nuclear form
      of Fibroblast growth Factor Receptor 1 (FGFR1) in a central role directing the
      post-mitotic development of neural cells through coordinated gene expression. In
      this review, we discuss in detail the current knowledge of FGFR1 nuclear
      interaction partners in three scenarios: (i) Engagement of FGFR1 in neuronal stem
      cells and regulation of neuronal differentiation; (ii) interaction with the
      orphan receptor Nurr1 in development of mesencephalic dopaminergic neurons; (iii)
      modulation of nuclear FGFR1 interactions downstream of nerve growth factor (NGF)
      signaling. These coalitions demonstrate the versatility of non-canonical, nuclear
      tyrosine kinase signaling in diverse cellular differentiation programs of
      neurons.

PMID- 25966816
TI  - Association of visceral fat area with chronic kidney disease and metabolic
      syndrome risk in the general population: analysis using multi-frequency
      bioimpedance.
AB  - BACKGROUND/AIMS: Advances in bioimpedance analysis (BIA) technologies now enable
      visceral fat area (VFA) to be assessed using this method. The aim of this study
      was to evaluate the clinical relevance and usefulness of VFA as a predictor of
      chronic kidney disease (CKD) and metabolic syndrome (MS), using BIA. METHODS: We
      identified 24,791 adults who underwent voluntary routine health checkups at
      Yeungnam University Hospital. In total 22,480 patients were recruited into our
      study. Participants were divided into 3 tertiles based on their VFA: low, middle,
      and high tertiles. CKD was defined as an estimated glomerular filtration rate
      (eGFR) <60 mL/min/1.73m(2). RESULTS: The higher tertile of VFA was associated
      with a higher prevalence of diabetes mellitus, hypertension, and male sex. Waist
      to-hip ratio, body mass index, blood pressure, lean mass, body fat %, and fasting
      glucose, total cholesterol, triglyceride, GGT, AST, ALT, and uric acid levels all
      increased as the VFA tertile increased (P < 0.001 for all variables). The
      prevalence of CKD was 6.9% in the low tertile, 13.9% in the middle tertile, and
      25.2% in the high tertile (P < 0.001). The prevalence of MS was 2.2% in the low
      tertile, 12.8% in the middle tertile, and 36.7% in the high tertile (P < 0.001).
      The AUROC values for VFA were higher than those for BMI and WHR. For VFA, the
      sensitivity and specificity for predicting CKD were 62.66% (95% CI, 61.0-64.3)
      and 64.22% (95% CI, 63.5-64.9), respectively, and 77.65% (95% CI, 76.3-79.0), and
      68.81% (95% CI, 68.1-69.5), respectively for predicting MS. CONCLUSION: Our
      results demonstrated that the VFA, measured by BIA, is a simple method for
      predicting the risk of CKD and MS.

PMID- 25966818
TI  - Epidemiology and Comorbidity in Children with Psoriasis and Atopic Eczema.
AB  - BACKGROUND: First studies have shown that juvenile psoriasis is associated with
      an increased prevalence of comorbidity. OBJECTIVES: We carried out a data
      analysis to characterise the profiles of comorbidity in children with psoriasis
      and atopic eczema. METHODS: Prevalence data were derived from the database of a
      German statutory health insurance company according to ICD-10 codes L40
      (psoriasis) and L20 (atopic eczema) of children up to 18 years insured in 2009.
      RESULTS: Data sets included 1.64 million persons and 293,181 children. 1,313
      children = 0.45% (0.42-0.47) had a diagnosis of psoriasis and 30,354 = 10.35%
      (10.24-10.47) had a diagnosis of atopic eczema. Obesity, hyperlipidaemia,
      arterial hypertension and diabetes were more often diagnosed in children with
      psoriasis in comparison to all children without psoriasis and to those with
      atopic eczema. CONCLUSION: Children with psoriasis and atopic eczema show
      different and specific patterns of comorbidity which should be detected early and
      treated adequately.

PMID- 25966819
TI  - Mechanism of cell integration on biomaterial implant surfaces in the presence of
      bacterial contamination.
AB  - Bacterial contamination during biomaterial implantation is often unavoidable,
      yielding a combat between cells and bacteria. Here we aim to determine the
      modulatory function of bacterial components on stem-cell, fibroblast, and
      osteoblast adhesion to a titanium alloy, including the role of toll-like
      receptors (TLRs). Presence of heat-sacrificed Staphylococcus epidermidis,
      Staphylococcus aureus, Escherichia coli, or Pseudomonas aeruginosa induced dose
      and cell-type dependent responses. Stem-cells were most sensitive to bacterial
      presence, demonstrating decreased adhesion number yet increased adhesion effort
      with a relatively large focal adhesion contact area. Blocking TLRs had no effect
      on stem-cell adhesion in presence of S. aureus, but blocking both TLR2 and TLR4
      induced an increased adhesion effort in presence of E. coli. Neither
      lipopolysaccharide, lipoteichoic acid, nor bacterial DNA provoked the same cell
      response as did whole bacteria. Herewith we suggest a new mechanism as to how
      biomaterials are integrated by cells despite the unavoidable presence of
      bacterial contamination. Stimulation of host cell integration of implant surfaces
      may open a new window to design new biomaterials with enhanced healing, thereby
      reducing the risk of biomaterial-associated infection of both "hardware-based"
      implants as well as of tissue-engineered constructs, known to suffer from
      similarly high infection risks as currently prevailing in "hardware-based"
      implants.

PMID- 25966817
TI  - Chemical ligation of the influenza M2 protein for solid-state NMR
      characterization of the cytoplasmic domain.
AB  - Solid-state NMR-based structure determination of membrane proteins and large
      protein complexes faces the challenge of limited spectral resolution when the
      proteins are uniformly (13)C-labeled. A strategy to meet this challenge is
      chemical ligation combined with site-specific or segmental labeling. While
      chemical ligation has been adopted in NMR studies of water-soluble proteins, it
      has not been demonstrated for membrane proteins. Here we show chemical ligation
      of the influenza M2 protein, which contains a transmembrane (TM) domain and two
      extra-membrane domains. The cytoplasmic domain, which contains an amphipathic
      helix (AH) and a cytoplasmic tail, is important for regulating virus assembly,
      virus budding, and the proton channel activity. A recent study of uniformly (13)C
      labeled full-length M2 by spectral simulation suggested that the cytoplasmic tail
      is unstructured. To further test this hypothesis, we conducted native chemical
      ligation of the TM segment and part of the cytoplasmic domain. Solid-phase
      peptide synthesis of the two segments allowed several residues to be labeled in
      each segment. The post-AH cytoplasmic residues exhibit random-coil chemical
      shifts, low bond order parameters, and a surface-bound location, thus indicating
      that this domain is a dynamic random coil on the membrane surface. Interestingly,
      the protein spectra are similar between a model membrane and a virus-mimetic
      membrane, indicating that the structure and dynamics of the post-AH segment is
      insensitive to the lipid composition. This chemical ligation approach is
      generally applicable to medium-sized membrane proteins to provide site-specific
      structural constraints, which complement the information obtained from uniformly
      (13)C, (15)N-labeled proteins.

PMID- 25966820
TI  - Atypical presentation of human bocavirus: Severe respiratory tract infection
      complicated with encephalopathy.
AB  - Human bocavirus (HBOV) has been reported as a worldwide distributed respiratory
      pathogen. It has also been associated with encephalitis recently by detection of
      the virus in cerebrospinal fluid (CSF) of patients presented with encephalitis.
      This retrospective study aimed to present clinical features of HBOV infections in
      children with respiratory symptoms and describe unexplained encephalopathy in a
      subgroup of these patients. Results of 1,143 pediatric nasal samples from mid
      December 2013 to July 2014 were reviewed for detection of HBOV. A multiplex real
      time polymerase chain reaction assay was used for viral detection. Medical
      records of the patients were retrospectively analyzed. HBOV was detected in 30
      patients (2.6%). Median age was 14 months (5-80). Clinical diagnoses were upper
      respiratory tract infection (n = 10), bronchopneumonia (n = 9), acute
      bronchiolitis (n = 5), pneumonia (n = 4), acute bronchitis (n = 1), and asthma
      execarbation (n = 1). Hospitalization was required in 16 (53.3%) patients and 10
      (62.5%) of them admitted to pediatric intensive care unit (PICU). Noninvasive
      mechanical ventilation modalities was applied to four patients and mechanical
      ventilation to four patients. Intractable seizures developed in four patients
      while mechanically ventilated on the 2nd-3rd days of PICU admission. No specific
      reason for encephalopathy was found after a thorough investigation. No mortality
      was observed, but two patients were discharged with neurological sequela. HBOV
      may lead to respiratory infections in a wide spectrum of severity. This report
      indicates its potential to cause severe respiratory infections requiring PICU
      admission and highlights possible clinical association of HBOV and
      encephalopathy, which developed during severe respiratory infection.

PMID- 25966821
TI  - A universal strategy for aptamer-based nanopore sensing through host-guest
      interactions inside alpha-hemolysin.
AB  - Nanopore emerged as a powerful single-molecule technique over the past two
      decades, and has shown applications in the stochastic sensing and biophysical
      studies of individual molecules. Here, we report a versatile strategy for
      nanopore sensing by employing the combination of aptamers and host-guest
      interactions. An aptamer is first hybridized with a DNA probe which is modified
      with a ferrocene?cucurbit[7]uril complex. The presence of analytes causes the
      aptamer-probe duplex to unwind and release the DNA probe which can quantitatively
      produce signature current events when translocated through an alpha-hemolysin
      nanopore. The integrated use of magnetic beads can further lower the detection
      limit by approximately two to three orders of magnitude. Because aptamers have
      shown robust binding affinities with a wide variety of target molecules, our
      proposed strategy should be universally applicable for sensing different types of
      analytes with nanopore sensors. 

PMID- 25966822
TI  - Coexistence of Calcification, Intraplaque Hemorrhage and Lipid Core within the
      Asymptomatic Atherosclerotic Carotid Plaque: The Rotterdam Study.
AB  - BACKGROUND: There is a growing amount of evidence suggesting that the composition
      of carotid atherosclerotic plaques may be of clinical relevance. Yet, little is
      known on the coexistence of potentially vulnerable and stabilizing components
      within asymptomatic plaques. Therefore, in this study we set out to investigate
      the coexistence of intraplaque calcification, hemorrhage and lipid core within
      the carotid artery using a multi-modality imaging approach. METHODS: In 329
      subjects from the population-based Rotterdam Study, all with ultrasound-confirmed
      carotid wall thickening, we performed a multi-detector CT and a high-resolution
      MRI of the carotid artery bifurcation at both sides. On the CT examinations, we
      quantified the volume of intraplaque calcification, and using the MRI
      examinations we rated the presence of intraplaque hemorrhage and of lipid core.
      In total, we investigated 611 carotid arteries with plaques. With logistic
      regression models we investigated the relationship of calcification volume - as a
      potential stabilizing component - with the presence of potential vulnerable
      components (intraplaque hemorrhage and lipid core) within each carotid plaque. We
      adjusted all analyses for age, sex and maximal plaque thickness. Next, we
      stratified on degree of stenosis (<= or >30%) to evaluate effect modification by
      atherosclerotic burden. RESULTS: We found that a larger calcification volume was
      associated with a higher prevalence of intraplaque hemorrhage, and a lower
      prevalence of lipid core (fully-adjusted odds ratio (OR) per standard deviation
      (SD) increase in calcification volume: 2.04 (95% confidence intervals (CI): 1.49;
      2.78) and 0.72 (95% CI: 0.58; 0.90), respectively). Stratification on the degree
      of stenosis showed no difference in the association between calcification volume
      and hemorrhage over strata, while the relationship between a larger calcification
      volume and a lower prevalence of lipid seemed more pronounced in persons with a
      high degree of stenosis. CONCLUSIONS: In this population-based setting, we found
      that there is a complex relationship between calcification, intraplaque
      hemorrhage and lipid core within the carotid atherosclerotic plaque. Plaques with
      a higher load of calcification contain more often hemorrhagic components, but
      less often lipid core. Our results suggest that both in small and large plaques,
      intraplaque calcification may not be a stabilizing factor per se. These findings
      create an urge for conducting prospective studies investigating the interrelation
      of these different plaque components with regard to future cerebrovascular
      events.

PMID- 25966823
TI  - Impact of Neoadjuvant Chemotherapy on Postoperative Morbidity after Gastrectomy
      for Gastric Cancer.
AB  - BACKGROUND/AIMS: Patients with locally advanced gastric cancer benefit from
      neoadjuvant chemotherapy. Potential disadvantages of neoadjuvant chemotherapy
      include increased surgical complications, leading to increased postoperative
      morbidity. METHODS: We retrospectively studied medical records of 135 patients
      with resectable cancer of the stomach who underwent gastrectomy between 2002 and
      2009. The impact of neoadjuvant chemotherapy on postoperative morbidity was
      investigated. We compared demographic, clinical and operative data, morbidity and
      mortality from 105 patients who received surgical treatment immediately after
      diagnosis (SURG group), versus 30 patients who first received neoadjuvant
      chemotherapy (CHEMO group). RESULTS: Demographic, clinical and surgical procedure
      parameters did not differ significantly between both groups. Postoperative
      morbidity was 46.7% in CHEMO- and 41.9% in SURG-patients (p = 0.680). There were
      eight cases of death, 2/30 (6.7%) in CHEMO and 6/105 (5.7%) in the SURG group (p
      = 1). The overall complications according to Clavien-classification did not
      differ significantly (p = 0.455). The wound infection rate (23.3 vs. 3.8%; p =
      0.002) and insufficiency of the duodenal stump (13.3 vs. 1.9%; p = 0.022) were
      significantly higher in the CHEMO group. CONCLUSION: This study showed no
      significant impact of neoadjuvant chemotherapy on postoperative morbidity after
      gastrectomy using the Clavien-classification. Only an increase in wound
      infections in CHEMO compared with the SURG group were noted. Therefore,
      neoadjuvant chemotherapy can be considered safe and feasible.

PMID- 25966824
TI  - A 4-Year, Open-Label, Multicenter, Randomized Trial of Genotropin(r) Growth
      Hormone in Patients with Idiopathic Short Stature: Analysis of 4-Year Data
      Comparing Efficacy, Efficiency, and Safety between an Individualized, Target
      Driven Regimen and Standard Dosing.
AB  - BACKGROUND/AIMS: Growth hormone (GH) treatment regimens for children with non-GH
      deficient, idiopathic short stature (ISS) have not been optimized. To compare the
      efficacy, efficiency, and safety of an individualized, target-driven GH regimen
      with standard weight-based dosing after 4 years of treatment. METHODS: This is a
      4-year, open-label, multicenter, randomized trial comparing individualized,
      formula-based dosing of Genotropin(r) versus a widely used ISS dose of
      Genotropin(r). Subjects were prepubertal, had a bone age of 3-10 years for males
      and 3-9 years for females, were naive to GH treatment, and had a height standard
      deviation score (Ht SDS) of -3 to -2.25, a height velocity <25th percentile for
      their bone age, and peak stimulated GH >10 ng/ml. After the first 2 years, the
      individualized-dosing group was further randomized to either 0.18 or 0.24
      mg/kg/week. RESULTS: At 4 years, subjects in all treatment regimens achieved
      similar average height gains of +1.3 SDS; however, the individualized dosing
      regimen utilized less GH to achieve an equivalent height gain. CONCLUSION:
      Individualized, formula-based GH dosing, followed by a dose reduction after 2
      years, provides a more cost-effective growth improvement in patients with ISS
      than currently employed weight-based regimens.

PMID- 25966825
TI  - Association Between Mitral Annular Calcium and Flail Mitral Leaflet in
      Degenerative Mitral Valve Disease.
AB  - The aim of this study was to assess the association between mitral annular
      calcium (MAC) and flail mitral leaflets in a cohort of patients with degenerative
      mitral valve disease. A retrospective study was conducted of consecutive patients
      with degenerative mitral valve disease who underwent echocardiography at Rabin
      Medical Center from 2003 to 2012. Special focus was attended to the presence and
      grade of MAC and characterization of valve pathology (myxomatous vs
      nonmyxomatous, prolapse vs flail). Patients were excluded if they had undergone
      previous mitral valve surgery and/or had infective endocarditis. Multivariate
      logistic regressions were used to control for confounders. The study included
      1,912 patients (60.8% men, mean age 63.8 +/- 17.4 years) divided into 3 groups:
      1,627 (86%) without MAC, 183 (10%) with either mild or moderate MAC, and 94 (5%)
      with severe MAC. The presence of flail leaflet was 27%, 30%, and 46% in these
      groups, respectively (p <0.001). After adjustment for age, gender, and co
      morbidities, the odd ratio for flail mitral leaflet with severe MAC versus no MAC
      was 1.76 (95% confidence interval 1.10 to 2.83, p = 0.019). In conclusion, this
      study demonstrates that degenerative mitral valve disease with severe MAC is
      significantly associated with flail mitral leaflet.

PMID- 25966826
TI  - Impact of visit-to-visit variability and systolic blood pressure control on
      subsequent outcomes in hypertensive patients with coronary artery disease (from
      the HIJ-CREATE substudy).
AB  - Although visit-to-visit variability in systolic blood pressure (BP) is a strong
      predictor of stroke, the impact on subsequent major adverse cardiac events
      (MACEs) in patients with coronary artery disease (CAD) in terms of secondary
      prevention remains unclear. The aim of this study was to clarify the prognostic
      significance of visit-to-visit variability in systolic BP on subsequent MACE in
      hypertensive patients with CAD. In the Heart Institute of Japan Candesartan
      Randomised Trial for Evaluation in Coronary Artery Disease, a total of 2,049
      hypertensive patients with CAD were enrolled. Incidence of MACEs in addition to
      biochemistry tests and office BP were determined during follow-up. Achieved BP
      was defined as the mean value of systolic BP in patients who did not experience
      MACE and the mean value of systolic BP before MACE in those who experienced MACE
      during follow-up. In the present study, 1,734 patients had multiple follow-up
      visits (>=3 times) until their final follow-up. During a median follow-up of 4.2
      years, the primary outcome occurred in 317 patients (18.3%). Visit-to-visit
      variability of systolic BP was defined as the SD. Participants were divided into
      equal quartiles based on the mean systolic BP during follow-up and visit-to-visit
      variability of systolic BP, respectively. Although there was no relation between
      visit-to-visit variability of systolic BP and the incidence of MACE, the highest
      quartile based on mean systolic BP showed a significant relation with subsequent
      MACE. In conclusion, in hypertensive patients with CAD, inadequate BP control is
      a strong predictor of subsequent MACE, whereas visit-to-visit variability of
      systolic BP is not.

PMID- 25966827
TI  - Oral perception of liquid volume changes with age.
AB  - Bolus volume has been widely studied, and research has demonstrated a variety of
      physiological impacts on swallowing and swallowing disorders. Oral perception of
      bolus volume has not, to our knowledge, been investigated in association with
      normal ageing processes. Research suggests many sensory changes with age, some
      within the oral cavity, and changes in swallowing function with age have been
      defined. The role of perception in oropharyngeal deglutition with age requires
      further investigation. The purpose of this study was to establish the
      psychophysical relationship between liquid volume and oral perception and examine
      changes with age. Healthy young and older adults were prospectively assessed
      using a magnitude estimation task differentiating five volumes of water delivered
      randomly to the oral cavity. Results suggest a fourfold increase in liquid volume
      is required by older participants to perceive an approximate twofold increase in
      the perception of volume compared with younger healthy adults. Sensory receptors
      in the oral cavity provide a feedback loop that modulates the swallowing motor
      response so that it is optimal for the size and consistency of the bolus. Changes
      in perception of bolus volume with age are consistent with other perceptual
      changes and may provide valuable information regarding sensorineural
      rehabilitation strategies in the future. 

PMID- 25966828
TI  - Red blood cell distribution width predicts responsiveness of acute pulmonary
      vasodilator testing in patients with idiopathic pulmonary arterial hypertension.
AB  - BACKGROUND: Red blood cell distribution width (RDW) has been shown to predict
      clinical outcomes in cardiopulmonary vascular diseases. We investigated whether
      RDW is useful to predict responsiveness of acute pulmonary vasodilator testing in
      patients with idiopathic pulmonary arterial hypertension (IPAH). METHODS: RDW was
      determined in 167 IPAH patients who underwent acute pulmonary vasodilator
      testing. All subjects were followed up for 20 +/- 10 months. RESULTS: Nineteen
      out of 167 patients (11.4%) were acute pulmonary vasodilator testing responders.
      Patients with lower RDW levels <= 13.65% (sensitivity 89.5%, specificity 52.7%;
      AUC: 0.747, 95% CI: 0.632 to 0.861) were more likely to have a positive response.
      Multivariate logistic regression analysis showed that RDW <= 13.65% independently
      predicted responsiveness of vasodilator testing in patients with IPAH (OR 18.453,
      95% CI 2.279-149.391, p = 0.006). RDW correlated with disease severity evaluated
      by clinical parameters. Patients with increased RDW (> 13.65%) had significantly
      increased risk of all-cause death (Log-rank p = 0.007). CONCLUSIONS: RDW
      independently predicts responsiveness of acute pulmonary vasodilator testing in
      patients with IPAH. RDW is associated with disease severity and all-cause death.

PMID- 25966829
TI  - Label-free and dual-amplified detection of protein via small molecule-ligand
      linked DNA and a cooperative DNA machine.
AB  - Sensitive detection of protein is essential for both molecular diagnostics and
      biomedical research. Here, taking folate receptor as the model analyte, we
      developed a label-free and dual-amplified strategy via small molecular-ligand
      linked DNA and a cooperative DNA machine which could perform primary
      amplification and mediate secondary amplification simultaneously. Firstly, the
      specific binding of folate receptor to the small-molecule folate which linked to
      a trigger DNA could protect the trigger DNA from exonuclease I digestion,
      translating folate receptor detection into trigger DNA detection. Subsequently,
      trigger DNA initiated the DNA machine through hybridizing with the hairpin of the
      DNA machine, resulting in hairpin conformational change and stem open. The open
      stem further hybridized with a primer which initiated circular strand
      displacement polymerization reaction; meanwhile the rolling circle amplification
      templates which were initially blocked in the DNA machine were liberated to
      mediate rolling circle amplification. In such a working model, the DNA machine
      achieved cooperatively controlling circular strand-displacement polymerization
      reaction and rolling circle amplification, realizing dual-amplification. Finally,
      the rolling circle amplification process synthesized a long repeated G-quadruplex
      sequence, which strongly interacted with N-methyl mesoporphyrin IX, bringing
      label-free fluorescence signal. This strategy could detect folate receptor as low
      as 0.23 pM. A recovery over 90% was obtained when folate receptor was detected in
      spiked human serum, demonstrating the feasibility of this detection strategy in
      biological samples.

PMID- 25966830
TI  - Electronic structure and conformational flexibility of D-cycloserine.
AB  - The first comprehensive investigation of the effect of conformational flexibility
      of gaseous D-cycloserine on the valence and core electronic structures is
      reported here. The seven most stable conformers among the twelve structures
      calculated at the MP2/6-311++G** level of theory were assumed to properly
      describe the properties of the investigated compound. Taking into account the
      contribution of these isomers, the valence photoelectron spectrum (UPS) was
      simulated by the Outer Valence Green' s Function (OVGF) method. A different
      sensitivity towards the conformational flexibility of the outermost photoelectron
      bands was exhibited in the simulated spectrum. The comparison of the theoretical
      UPS with the experimental one allowed a detailed assignment of the outermost
      valence spectral region. The composition and bonding properties of the relevant
      MOs of the most stable conformers were analyzed in terms of leading Natural Bond
      Orbital (NBO) contributions to the HF/6-311++G** canonical MOs. The C1s, N1s, and
      O1s photoelectron spectra (XPS) were theoretically simulated by calculating the
      vertical Ionization Energies (IEs) of the relevant conformers using the DeltaSCF
      approach. The different IE chemical shift spread of the XPS components associated
      with various conformers, which is expected to affect the experimental spectra,
      could be evaluated by simulated XPS, thus providing a new insight into the core
      electronic structure. The comparison of the theoretical results with the
      experimental ones unraveled that the atomic XPS components are not mixed by
      conformational flexibility of D-cycloserine, and that the specific vibronic
      structure of different spectral components should play a crucial role in
      determining different relative intensities and band shapes observed in the
      experiment.

PMID- 25966831
TI  - Reproducibility of biomarkers in induced sputum and in serum from chronic
      smokers.
AB  - RATIONALE: Soluble inflammatory markers obtained from non-invasive airway
      sampling such as induced sputum may be useful biomarkers for targeted
      pharmaceutical interventions. However, before these soluble markers can be used
      as potential targets, their variability and reproducibility need to be
      established in distinct study populations. OBJECTIVE: This study aimed to assess
      the reproducibility of biomarkers obtained from induced sputum and serum in
      chronic smokers and non-smokers. METHOD: Sputum and serum samples were obtained
      from 16 healthy non-smokers and 16 asymptomatic chronic smokers (for both groups:
      8M/8F, 30-52 years, FEV1 >=80% pred.; >=10 pack years for the smokers) on 2
      separate visits 4-10 days apart. Soluble markers in serum and sputum were
      analysed by ELISA. The differences between smokers vs non-smokers were analysed
      with a t-test and variability was assessed on log-transformed data by a mixed
      model ANOVA. RESULTS: Analysable sputum samples could be obtained from all 32
      subjects. In both study populations neutrophils and macrophages were the
      predominant cell types. Serum Pulmonary Surfactant Associated Protein D had
      favourable reproducibility criteria for reliability ratio (0.99), intra-subject
      coefficient of variation (11.2%) and the Bland Altman limits of agreement.
      Furthermore, chronic smokers, compared to non-smokers, had significantly higher
      sputum concentrations of IL-8 (1094.6 pg/mL vs 460.8 pg/mL, p = 0.006)), and
      higher serum concentrations of Pulmonary Surfactant Associated Protein D (110.9
      pg/mL vs 64.7 pg/mL, p = 0.019), and lower concentrations of Serum Amyloid A
      (1352.4 pg/mL vs 2297.5 pg/mL, p = 0.022). CONCLUSION: Serum Pulmonary Surfactant
      Associated Protein D proved to be a biomarker that fulfilled the criteria for
      reproducibility in both study groups.

PMID- 25966832
TI  - VCD spectroscopy as an excellent probe of chiral metal complexes containing a
      carbon monoxide vibrational chromophore.
AB  - Vibrational circular dichroism, VCD, gives evidence that the carbon monoxide
      chromophore in a heteroleptic cyclopentadienyl Ru(ii)-carbonyl complex is very
      sensitive to the chirality of the metal centre and becomes an excellent probe to
      define the configuration of chiral metal complexes. 

PMID- 25966833
TI  - The Portuguese Journal of Pulmonology and other Portuguese Society of Pulmonology
      publications.

PMID- 25966834
TI  - Recommendations for the diagnosis and treatment of latent and active tuberculosis
      in inflammatory joint diseases candidates for therapy with tumor necrosis factor
      alpha inhibitors - March 2008 update.
AB  - The Portuguese Society of Rheumatology and the Portuguese Society of Pulmonology
      have updated the guidelines for the diagnosis and treatment of latent
      tuberculosis infection (LTBI) and active tuberculosis (ATB) in patients with
      inflammatory joint diseases (IJD) that are candidates to therapy with tumour
      necrosis factor alpha (TNFalpha) antagonists. In order to reduce the risk of
      tuberculosis (TB) reactivation and the incidence of new infections, TB screening
      is recommended to be done as soon as possible, ideally at the moment of IJD
      diagnosis, and patient assessment repeated before starting anti-TNFalpha therapy.
      Treatment for ATB and LTBI must be done under the care of a TB specialist. When
      TB treatment is indicated, it should be completed prior to starting anti-TNFalpha
      therapy. If the IJD activity justifies the need for immediate treatment, anti
      TNFalpha therapy can be started two months after antituberculous therapy has been
      initiated, in the case of ATB, and one month after in the case of LTBI. Chest X
      ray is mandatory for all patients. If Gohn's complex is present, the patient
      should be treated for LTBI; healed lesions require the exclusion of ATB. In cases
      of suspected active lesions, ATB should be excluded/confirmed and adequate
      therapy initiated. Tuberculin skin test, with two units of RT23, should be
      performed in all patients. If the induration is <5 mm, the test should be
      repeated within 1 to 2 weeks, on the opposite forearm, and will be considered
      negative only if the result is again <5 mm. Positive TST implicates LTBI
      treatment, unless previous proper treatment was provided. If TST is performed in
      immunossuppressed IJD patients, LTBI treatment should be offered to the patient
      before starting anti-TNF-alpha therapy, even in the presence of a negative test,
      after risk / benefit assessment. Rev Port Pneumol 2007; XIV (2): 271-283. 

PMID- 25966835
TI  - Mechanical Tension Promotes the Osteogenic Differentiation of Rat Tendon-derived
      Stem Cells Through the Wnt5a/Wnt5b/JNK Signaling Pathway.
AB  - BACKGROUND/AIMS: Tendinopathy is a common sports injury that is manifested by the
      heterotopic ossification of tendon tissue. Tendon stem cells (TSCs) are prone to
      osteogenic differentiation under excessive tension. The underlying mechanisms
      remain poorly understood. METHODS: Uniaxial mechanical tension (UMT) served to
      stretch rat tendon-derived stem cells (rTDSCs) at 8% elongation (frequency: 1 Hz;
      48, 60, or 72 hours). RESULTS: The osteogenic differentiation of rTDSCs appeared
      after UMT along with increased mRNA expression of the osteogenic genes Runx2,
      Dlx5, Alpl, and Col1a1 and increased Runx2 protein expression. Wnt5a, Wnt5b and P
      JNK protein levels were also upregulated after UMT stimulation. The inhibition of
      JNK expression by SP600125 and JNK1-shRNA decreased UMT-induced Runx2 protein
      expression, and the activation of JNK expression by anisomycin and JNK1-cDNA
      increased UMT-induced Runx2 protein expression. When shRNA knocked down Wnt5a and
      Wnt5b expression in rTDSCs, the induction of Runx2 and P-JNK expression by UMT
      was reduced. The inhibition of Runx2 expression could be rescued by the
      activation of JNK expression by anisomycin. CONCLUSION: UMT induced the
      osteogenic differentiation of rTDSCs via the Wnt5a/Wnt5b/JNK signaling pathway.
      Accordingly, this pathway may influence the heterotopic ossification of tendon
      tissue subjected to excessive tension.

PMID- 25966837
TI  - Concerns, Barriers, and Recommendations to Improve Transition from Pediatric to
      Adult IBD Care: Perspectives of Patients, Parents, and Health Professionals.
AB  - BACKGROUND: The current transition literature is a fragmented assortment of
      studies examining select subsections of transition stakeholders. METHODS:
      Adolescent/young adult patients with IBD (40% transferred to adult care),
      parents, and health providers (53.8% adult providers) participated in 1 of 6
      focus group interviews focused on concerns and needs surrounding transition to
      adult care. Data were analyzed through directed content analysis. RESULTS:
      Transition needs/concerns focused on (1) losing relationships with pediatric
      providers, (2) perceptions of poorer quality care from adult providers, (3) high
      parent involvement preventing the development of youth self-management skills,
      and (4) finances and insurance. Suggestions to improve transition to adult care
      included the following: (1) meeting alone with adolescents during appointments,
      (2) providing concrete guidance on how/when to transition responsibility, and (3)
      increasing accountability for adolescents. Recommendations to improve transfer
      included the following: (1) providing more information about the transfer process
      and adult providers, (2) obtaining peer support and mentoring, and (3) setting
      goals and deadlines for transfer. CONCLUSIONS: Inclusion of several stakeholder
      groups allowed for the identification of commonalities across groups as well as
      their unique needs and concerns surrounding transition to adult care. Concerns
      and recommendations by participants should be targeted in future transition
      program efforts.

PMID- 25966836
TI  - PharmGKB summary: Efavirenz pathway, pharmacokinetics.

PMID- 25966838
TI  - Systematic Review of the Clinical Disease Severity Indices for Inflammatory Bowel
      Disease.
AB  - BACKGROUND: Clinical disease severity indices are increasingly being used in
      choosing treatment and monitoring the response of patients with inflammatory
      bowel disease (IBD). The aim of this study was to systematically review the
      clinical disease severity indices in IBD and to appraise their measurement
      properties and methodological quality. METHODS: We searched the MEDLINE, Embase,
      and PsycINFO databases for original articles describing the development and/or
      evaluation of one or more of the measurement properties of clinical disease
      severity indices used in IBD. We assessed these properties (e.g., internal
      consistency, reliability, validity, responsiveness) using a standardized
      checklist. RESULTS: We examined the full text of 142 articles that we deemed
      potentially eligible and identified 22 clinical disease severity indices in IBD.
      No clinical disease index has met all the required measurement properties. All of
      the validation studies were not descriptive enough to allow assessment of their
      methodology. CONCLUSIONS: Although commonly used in multiple clinical trials,
      none of the clinical disease severity indices in IBD had all the required
      measurement properties. Further validation studies are required.

PMID- 25966839
TI  - Immunizations in Pediatric and Adult Patients with Inflammatory Bowel Disease: A
      Practical Case-based Approach.
AB  - As the treatment of inflammatory bowel disease (IBD) becomes more complex and
      increasingly relies on combinations of immunosuppression in patients with
      moderate to severe ulcerative colitis or Crohn's disease, the provider must be
      aware of recommendations for the appropriate use of vaccines-both inactivated and
      live. The timing and type of vaccination required may be altered based on the
      underlying medical treatment for the IBD. In some instances, titers may be
      required to assess for vaccine response. Vaccination recommendations have changed
      dramatically over the past 5 years with direct implications for the protection of
      the patients with IBD. There are several newly licensed vaccines and new
      recommendations by the U.S. Advisory Committee on Immunization Practices and
      Infectious Diseases Society of America defining degrees of immunosuppression and
      the use of certain live vaccines based on these levels. This review provides a
      case-based approach to vaccinating the pediatric and adult patients with IBD,
      with an emphasis on practicality. Case scenarios include children and adults with
      newly diagnosed and chronic IBD. Recommendations for vaccine management in these
      scenarios are provided, including special circumstances such as pregnancy and
      infant vaccinations when the mother is receiving immunosuppressive medication. 

PMID- 25966840
TI  - Compression and communication in the cultural evolution of linguistic structure.
AB  - Language exhibits striking systematic structure. Words are composed of
      combinations of reusable sounds, and those words in turn are combined to form
      complex sentences. These properties make language unique among natural
      communication systems and enable our species to convey an open-ended set of
      messages. We provide a cultural evolutionary account of the origins of this
      structure. We show, using simulations of rational learners and laboratory
      experiments, that structure arises from a trade-off between pressures for
      compressibility (imposed during learning) and expressivity (imposed during
      communication). We further demonstrate that the relative strength of these two
      pressures can be varied in different social contexts, leading to novel
      predictions about the emergence of structured behaviour in the wild. 

PMID- 25966841
TI  - Slip of the tongue: Implications for evolution and language development.
AB  - A prevailing theory regarding the evolution of language implicates a gestural
      stage prior to the emergence of speech. In support of a transition of human
      language from a gestural to a vocal system, articulation of the hands and the
      tongue are underpinned by overlapping left hemisphere dominant neural regions.
      Behavioral studies demonstrate that human adults perform sympathetic mouth
      actions in imitative synchrony with manual actions. Additionally, right
      handedness for precision manual actions in children has been correlated with the
      typical development of language, while a lack of hand bias has been associated
      with psychopathology. It therefore stands to reason that sympathetic mouth
      actions during fine precision motor action of the hands may be lateralized. We
      employed a fine-grained behavioral coding paradigm to provide the first
      investigation of tongue protrusions in typically developing 4-year old children.
      Tongue protrusions were investigated across a range of cognitive tasks that
      required varying degrees of manual action: precision motor action, gross motor
      action and no motor actions. The rate of tongue protrusions was influenced by the
      motor requirements of the task and tongue protrusions were significantly right
      biased for only precision manual motor action (p<.001). From an evolutionary
      perspective, tongue protrusions can drive new investigations regarding how an
      early human communication system transitioned from hand to mouth. From a
      developmental perspective, the present study may serve to reveal patterns of
      tongue protrusions during the motor development of typically developing children.

PMID- 25966842
TI  - Rapid synthesis of a PtRu nano-sponge with different surface compositions and
      performance evaluation for methanol electrooxidation.
AB  - A rapid strategy to synthesize a highly active PtRu alloy nano-sponge catalyst
      system for methanol electro-oxidation is presented. The greatly increased Pt
      utilization, anti-CO poisoning ability and electronic effect resulting from the
      porous nano-sponge structure could account for the performance improvement. 

PMID- 25966843
TI  - Use of selective serotonin re-uptake inhibitors and the heart rate corrected QT
      interval in a real-life setting: the population-based Rotterdam Study.
AB  - AIMS: Selective serotonin re-uptake inhibitors (SSRIs), specifically citalopram
      and escitalopram, are thought to cause QTc prolongation, although studies have
      shown contradictory results. Nevertheless, a maximum citalopram dosage of 20 mg
      in high risk patients (e.g. >60 years of age) is recommended. We aimed to
      investigate the association between use of (individual) SSRIs and QTc in a
      population-based study in older adults. METHODS: This study, which was part of
      the prospective Rotterdam Study (period 1991-2012), included participants with up
      to five electrocardiograms (ECGs). We used linear mixed models to compare QTc F
      (QT corrected according to Fridericia) measured during use of individual SSRIs
      with QTc F measured during non-use of any antidepressant. For citalopram,
      analyses were additionally restricted to a maximum dosage of 20 mg in
      participants aged 60 years and older. RESULTS: We included 12 589 participants
      with a total of 26 620 ECGs of which 436 ECGs were made during SSRI use. The mean
      QTc F was similar during use of any drugs from the SSRI class and during non-use.
      After stratifying to individual SSRIs, ECGs recorded during use of citalopram had
      the longest QTc compared with ECGs recorded during non-use (+12.8 ms, 90% CI 7.5,
      18.2). This result remained similar in the analysis comprising participants aged
      60 years and older with a maximum prescribed daily dosage of 20 mg citalopram.
      CONCLUSIONS: Although no SSRI class effect was observed, use of citalopram was
      associated with a longer QTc F, even after considering the recommended
      restrictions. Other SSRIs may not give a clinically relevant QTc F prolongation.

PMID- 25966844
TI  - Interactive regulation by the Bacillus subtilis global regulators CodY and ScoC.
AB  - CodY and ScoC are Bacillus subtilis transcriptional regulators that control the
      expression of dozens of genes and operons. Using scoC-lacZ fusions and DNA
      binding experiments, we show here that scoC is directly repressed by CodY. This
      effect creates multiple forms of cascade regulation. For instance, expression of
      the dtpT gene, which is directly and negatively controlled by ScoC and encodes a
      putative oligopeptide permease, was activated indirectly by CodY due to CodY
      mediated repression of scoC. The opp operon, which encodes an oligopeptide
      permease that is essential for sporulation and genetic competence development,
      proved to be a direct target of repression by both ScoC and CodY but was not
      significantly affected in codY or scoC single mutants. The combined actions of
      CodY and ScoC maintain opp repression when either one of the regulators loses
      activity but limit the level of repression to that provided by one of the
      regulators acting alone. Under conditions of nitrogen limitation, repression by
      ScoC of dtpT and opp was partly prevented by TnrA. Thus, the functioning of ScoC
      is determined by other transcription factors via modulation of its expression or
      DNA binding. 

PMID- 25966845
TI  - Long non-coding RNA ANRIL is upregulated in hepatocellular carcinoma and
      regulates cell apoptosis by epigenetic silencing of KLF2.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer
      related death, especially in China. And the mechanism of its progression remains
      poorly understood. Growing evidence indicates that long non-coding RNAs (lncRNAs)
      are found to be dysregulated in many cancers, including HCC. ANRIL, a lncRNA co
      clustered mainly with p14/ARF has been reported to be dysregulated in gastric
      cancer, esophageal squamous cell carcinoma, and lung cancer. However, its
      clinical significance and potential role in HCC are still not documented. METHODS
      AND RESULTS: In this study, expression of ANRIL was analyzed in 77 HCC tissues
      and matched normal tissues by using quantitative polymerase chain reaction (qRT
      PCR). ANRIL expression was upregulated in HCC tissues, and the higher expression
      of ANRIL was significantly correlated with tumor size and Barcelona Clinic Liver
      Cancer (BCLC) stage. Moreover, taking advantage of loss-of-function experiments
      in HCC cells, we found that knockdown of ANRIL expression could impair cell
      proliferation and invasion and induce cell apoptosis both in vitro and in vivo.
      We also found that ANRIL could epigenetically repress Kruppel-like factor 2
      (KLF2) transcription in HCC cells by binding with PRC2 and recruiting it to the
      KLF2 promoter region. We also found that SP1 could regulate the expression of
      ANRIL. CONCLUSION: Our results suggest that lncRNA ANRIL, as a growth regulator,
      may serve as a new biomarker and target for therapy in HCC.

PMID- 25966846
TI  - How to become an expert educator: a qualitative study on the view of health
      professionals with experience in patient education.
AB  - BACKGROUND: Health professionals with the level of competency necessary to
      provide high-quality patient education are central to meeting patients' needs.
      However, research on how competencies in patient education should be developed
      and health professionals trained in them, is lacking. The aim of this study was
      to investigate the characteristics of an expert educator according to health
      professionals experienced in patient education for patients with coronary heart
      disease, and their views on how to become an expert educator. METHODS: This
      descriptive qualitative study was conducted through individual interviews with
      health professionals experienced in patient education in cardiac care.
      Participants were recruited from cardiac care units and by using a snowball
      sampling technique. The interviews were audiotaped and transcribed verbatim. The
      data were analyzed with thematic approaches, using systematic text condensation.
      RESULTS: Nineteen Icelandic and Norwegian registered nurses, physiotherapists,
      and cardiologists, who had worked in cardiac care for 12 years on average,
      participated in the study. Being sensitive to the patient's interests and
      learning needs, and possessing the ability to tailor the education to each
      patient's needs and context of the situation was described as the hallmarks of an
      expert educator. To become an expert educator, motivation and active
      participation of the novice educator and a supportive learning environment were
      considered prerequisites. Supportive educational resources, observation and
      experiential training, and guidance from experienced educators were given as
      examples of resources that enhance competence development. Experienced educators
      expressed the need for peer support, inter-professional cooperation, and
      mentoring to further develop their competency. CONCLUSIONS: Expert patient
      educators were described as those demonstrating sensitivity toward the patient's
      learning needs and an ability to individualize the patient's education. A
      supportive learning environment, inner motivation, and an awareness of the value
      of patient education were considered the main factors required to become an
      expert educator. The experienced educators expressed a need for continuing
      education and peer support.

PMID- 25966848
TI  - Cycloexpansamines A and B: spiroindolinone alkaloids from a marine isolate of
      Penicillium sp. (SF-5292).

PMID- 25966847
TI  - Coffee and its waste repel gravid Aedes albopictus females and inhibit the
      development of their embryos.
AB  - BACKGROUND: Dengue is a prevalent arboviral disease and the development of
      insecticide resistance among its vectors impedes endeavors to control it. Coffee
      is drunk by millions of people daily worldwide, which is associated with the
      discarding of large amounts of waste. Coffee and its waste contain large amounts
      of chemicals many of which are highly toxic and none of which have a history of
      resistance in mosquitoes. Once in solution, coffee is brownish in colour,
      resembling leaf infusion, which is highly attractive to gravid mosquitoes. To
      anticipate the environmental issues related to the increasing popularity of
      coffee as a drink, and also to combat insecticide resistance, we explored the
      deterrence potentials of coffee leachates against the ovipositing and embryonic
      stages of the dengue vector, Aedes albopictus. METHODS: In a series of choice, no
      choice, and embryo toxicity bioassays, we examined changes in the ovipositional
      behaviours and larval eclosion of Ae. albopictus in response to coffee extracts
      at different concentrations. RESULTS: Oviposition responses were extremely low
      when ovicups holding highly concentrated extract (HCE) of coffee were the only
      oviposition sites. Gravid females retained increased numbers of mature eggs until
      5 days post-blood feeding. When provided an opportunity to oviposit in cups
      containing coffee extracts and with water, egg deposition occurred at lower rates
      in those containing coffee, and HCE cups were far less attractive to females than
      those containing water only. Females that successfully developed in a coffee
      environment preferentially oviposited in such cups when in competition with
      preferred oviposition sites (water cups), but this trait did not continue into
      the fourth generation. Larval eclosion occurred at lower rates among eggs that
      matured in a coffee environment, especially among those that were maintained on
      HCE-moistened substrates. CONCLUSIONS: The observations of the present study
      indicate a pronounced vulnerability of Ae. albopictus to the presence of coffee
      in its habitats during the early phases of its life cycle. The observations that
      coffee repels gravid females and inhibits larval eclosion provide novel
      possibilities in the search for novel oviposition deterrents and anti-larval
      eclosion agents against dengue vectors.

PMID- 25966849
TI  - Better visualization and photodocumentation of zone of inhibition by staining
      cells and background agar differently.

PMID- 25966850
TI  - Micromonospora endophytica sp. nov., an endophytic actinobacteria of Thai upland
      rice (Oryza sativa).
AB  - An actinobacterial strain, DCWR9-8-2(T), was isolated from a leaf of Thai upland
      rice (Oryza sativa) collected in Chumporn province, Thailand. Strain DCWR9-8-2(T)
      is Gram-stain-positive aerobic bacteria that produce single spores directly on
      the vegetative hypha. Cell wall peptidoglycan of this strain exhibits meso
      diaminopimelic acid and glycine, the reducing sugars of whole-cell hydrolysate
      are arabinose, glucose, ribose, xylose and small amount of mannose. The
      phospholipid profiles in the membrane are comprised of phosphatidylethanolamine,
      diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol,
      phosphatidylinositol mannosides. The major menaquinones are MK-9(H4) and MK
      10(H6). The diagnostic cellular fatty acids are iso-C16:0 and iso-C15:0. The G+C
      content of the genomic DNA is 72.5 mol%. The result of 16S rRNA sequence analysis
      of the strain revealed that this strain was closely related to Micromonospora
      auratinigra TT1-11(T) (99.25%). On the other hand, the result of gyrB gene
      sequence analysis revealed that this strain was closed to M. eburnea JCM 12345(T)
      (96.30%). In addition, a combination of DNA-DNA hybridization results and some
      phenotypic properties supported that this strain should be judged as a novel
      species of the genus Micromonospora, for which the name M. endophytica sp. nov.
      is proposed. The type strain is DCWR9-8-2(T) (=BCC 67267(T)=NBRC 110008(T)). 

PMID- 25966851
TI  - Botryoisocoumarin A, a new COX-2 inhibitor from the mangrove Kandelia candel
      endophytic fungus Botryosphaeria sp. KcF6.

PMID- 25966852
TI  - Discovery of secondary metabolites in an extractive liquid-surface immobilization
      system and its application to high-throughput interfacial screening of antibiotic
      producing fungi.
AB  - An extractive liquid-surface immobilization (Ext-LSI) system, which consists of a
      hydrophobic organic solvent (an upper phase), a fungal cell-ballooned microsphere
      layer (a middle phase) and a liquid medium (a lower phase), is a unique
      interfacial cultivation system for fungi. The fungal cells growing at the
      interface between the organic and aqueous phases efficiently produce hydrophobic
      metabolites, which are continuously extracted into the organic phase, and/or
      hydrophilic metabolites that migrate into the aqueous phase without carbon
      catabolite repression and product and/or feed-back inhibitions. Application of
      the system to fermentation of Penicillium multicolor IAM 7153 and Trichoderma
      atroviride AG2755-5NM398 afforded remarkably different profiles of secondary
      metabolites in the organic phase compared with those in an aqueous phase in
      traditional submerged cultivation (SmC). Various hydrophobic metabolites
      exhibiting unique UV-visible spectra were accumulated into the organic phase. The
      system was applied to a novel interfacial screening system of antibiotic
      producing fungi. Compared with the SmC, the interfacial cultivation system
      exhibited some interesting and important advantages, such as the higher
      accumulation of hydrophobic secondary metabolites, the lack of requirement for
      shaking and troublesome solvent extraction, and the small scale of the vessels
      (medium, 5 ml; dimethylsilicone oil, 1 ml), as well as the significantly
      different metabolite profiles. The interfacial screening system yielded a high
      incidence of antimicrobial activity, with 21.9% of the fungi tested exhibiting
      antifungal activity against Pichia anomala NBRC 10213. This novel interfacial
      high-throughput screening approach has the potential to discover new biologically
      active secondary metabolites even from strains previously found to be
      unproductive. 

PMID- 25966853
TI  - Structure-activity relationships of the plasminogen modulator SMTP with respect
      to the inhibition of soluble epoxide hydrolase.
AB  - A family of fungal metabolites, SMTP, is a small-molecule plasminogen modulator
      that enhances plasminogen activation, leading to thrombolysis. We recently
      demonstrated that SMTP-7 effectively treats ischemic stroke due to its
      thrombolytic activity as well as anti-inflammatory action, which is attributable
      to soluble epoxide hydrolase (sEH) inhibition. In this paper, we studied detailed
      structure-activity relationships of plasminogen modulation and sEH inhibition
      using 25 SMTP congeners including six newly synthesized ones. The results clearly
      demonstrate that the structure of the N-linked side chain of SMTP congeners
      markedly affect their activities toward plasminogen modulation and inhibitions of
      the two activities of sEH (C-terminal epoxide hydrolase and N-terminal
      phosphatase). A slight change in the N-linked side chain results in affording
      selectivity of SMTP congeners. Many congeners, which lacked plasminogen
      modulation activity, differently inhibited the two sEH activities depending on
      the structures of the N-linked side chain. Some congeners were active in
      plasminogen modulation and inhibition of both activities of sEH. These results
      help comprehensive understanding of ideal design of a drug useful for ischemic
      diseases that are associated with inflammation, such as stroke. 

PMID- 25966854
TI  - Asystole in the epilepsy unit.
AB  - BACKGROUND: Early identification of cardiac asystole as a reason for syncope is
      of uttermost significance, as insertion of a cardiac pacemaker can save the
      patient's life and prevent severe injury. The aim of this work was to emphasize
      the subtle and unusual presentations of asystole in patients evaluated in
      epilepsy units. METHODS: We reviewed the clinical presentation, ECG and EEG data
      of a series of seven patients who were evaluated in four epilepsy units and were
      diagnosed with asystole. RESULTS: Three patients had unusual clinical
      manifestations of cardiac asystole, resembling epileptic seizures. Three patients
      had asystole induced by epileptic seizures and in one patient the diagnosis was
      not clear. All patients except one were implanted with a pacemaker and improved
      clinically. CONCLUSIONS: Seizure-induced asystole is a rare complication of
      epilepsy and asystole may clinically mimic epileptic seizures. A high level of
      suspicion and thorough prolonged cardiac and EEG monitoring are mandatory for
      reaching the right diagnosis. As the diagnosis is rare and difficult to reach, a
      flow chart to assist diagnosis is suggested.

PMID- 25966855
TI  - Peritoneal Submesothelial Stromal Cells Support Hematopoiesis and Differentiate
      into Osteogenic and Adipogenic Cell Lineages.
AB  - The peritoneum is a thin membrane that covers most of the abdominal organs,
      composed of a monolayer of mesothelial cells and subjacent submesothelial loose
      connective tissue. Cells from the peritoneal wall are correlated with peritoneal
      fibrosis and epithelial-to-mesenchymal transition. However, the distinct
      involvement of mesothelial or submesothelial cells in such phenomena is still not
      clear. Here, we propose a new strategy to obtain stromal cells from anterior
      peritoneal wall explant cultures. These cells migrated from peritoneal tissues
      and proliferated in vitro for 4 weeks as adherent fibroblast-like cells. Optical
      and electronic microscopy analyses of the fragments revealed a significant
      submesothelial disorganization. The obtained cells were characterized as
      cytokeratin- vimentin+ laminin+ alpha-smooth muscle actin+, suggesting a
      connective tissue origin. Moreover, at the third passage, these stromal cells
      were CD90+CD73+CD29+Flk-1+CD45-, a phenotype normally attributed to cells of
      mesenchymal origin. These cells were able to support hematopoiesis, expressing
      genes involved in myelopoiesis (SCF, G-CSF, GM-CSF, IL-7 and CXCL-12), and
      differentiated into osteogenic and adipogenic cell lineages. The methodology
      demonstrated in this work can be considered an excellent experimental model to
      understand the physiology of the peritoneal wall in healthy and pathological
      processes. Moreover, this work shows for the first time that submesothelial
      stromal cells have properties similar to those of mesenchymal cells from other
      origins.

PMID- 25966856
TI  - Aortic valve and aortic diseases: update on current treatment options.

PMID- 25966857
TI  - Severe PMS/PMDD - is it time for a new approach?

PMID- 25966858
TI  - Reliable evidence from placebo-controlled, randomized, clinical trials for
      menopausal hormone therapy's influence on incidence and deaths from breast
      cancer.
AB  - In an invited editorial, Dr Shapiro proposes that vaginal bleeding leading to
      unblinding and subsequent detection bias explains the breast cancer increase seen
      with estrogen plus progestin in the Women's Health Initiative (WHI) clinical
      trial (1) . In the context of a uniform detection program of protocol-mandated
      annual mammography and breast examinations, such a proposal is medically
      implausible. Dr Shapiro suggests detection bias would identify a larger number of
      'slowly growing tumors that would otherwise remain clinically silent'. The
      findings of more advanced cancers with increased deaths from breast cancer in the
      estrogen plus progestin group refute this conjecture. During early post
      intervention phases of both WHI hormone therapy trials, when breast cancer
      detection bias is asserted by Dr Shapiro because participants had been informed
      of randomization assignment, breast cancer incidence rates were lower (rather
      than higher) than during intervention. Thus, Dr Shapiro's claims are directly
      refuted by findings from the WHI randomized clinical trials. Health-care
      providers should be aware that randomized clinical trial evidence supports
      estrogen plus progestin increasing breast cancer incidence and deaths from breast
      cancer. In contrast, among women with prior hysterectomy, randomized clinical
      trial evidence supports estrogen alone reducing breast cancer incidence and
      deaths from breast cancer. 

PMID- 25966859
TI  - Of conflicts, conspiracies, red herrings, and black swans.
AB  - The impact of the findings from the Women's Health Initiative trial of estrogen
      plus progestin cannot be attributed to any real or imagined conflicts of interest
      between government, researchers, and journals. Rather, the findings overturned
      decades of dogma in part promoted by the pharmaceutical industry, and the
      reaction to these unexpected findings was in direct proportion to their
      importance in reversing a misguided practice of prescribing the drug for chronic
      disease prevention. The findings have been widely accepted, as shown by the
      sustained subsequent reduction in prescriptions. However, conflicts of interest
      may influence a minority unwilling to accept the findings. The decrease in the
      use of a drug with an adverse risk profile for prevention of chronic disease is a
      public good. 

PMID- 25966860
TI  - Conflicts of interest in government-funded studies. A reply to red herrings.

PMID- 25966861
TI  - Conflicts of interest, smoke and mirrors.
AB  - Commercial funding of research studies may potentially influence or bias the
      findings and interpretation of results. An editorial on conflicts of interest
      suggested that funding from non-commercial sources, such as government agencies,
      may also represent a conflict of interest, and uses the Women's Health Initiative
      (WHI) as an example of how this might be. Two WHI investigators responded by
      claiming that the arguments put forward in the editorial were largely 'red
      herrings' and were aimed at disparaging the WHI results. But there is evidence of
      bias in the presentation and interpretation of WHI findings by some investigators
      which may be due to conflicts of interest. It is probably wise to declare all
      sources of external research funding, including industries, governments and
      charities, as conflicts of interest so that reviewers of such research studies
      are alerted to give them full scrutiny for evidence of external influences. 

PMID- 25966862
TI  - Use of the levonorgestrel intrauterine system in postmenopause.

PMID- 25966863
TI  - Author's reply: To PMID 24990143.

PMID- 25966864
TI  - Levonorgestrel and breast cancer risk - clarified.

PMID- 25966865
TI  - [Pain medication in nursing home residents with and without cancer. Most
      frequently with metamizole].
AB  - BACKGROUND: Pain is a highly prevalent symptom in nursing home residents. The
      analgesic pharmacotherapy of older adults is associated with challenges; however,
      studies from Germany examining the prescription pattern of analgesics in nursing
      home residents are rare. OBJECTIVES: This study was carried out to examine the
      prescription of analgesics in nursing home residents with and without the
      diagnosis of cancer. MATERIAL AND METHODS: Using health insurance claims data
      persons aged >= 65 years who were newly admitted to a nursing home between 2004
      and 2009 and who survived at least the first 90 days after admission were
      included in the study. Cancer was identified by outpatient diagnoses of malignant
      neoplasms (ICD-10: C00-C97). Prescription drugs within the first 90 days after
      admission to a nursing home were analyzed which means that aspirin and
      acetaminophen were not taken into account. RESULTS: A total of 5549 nursing home
      residents were included, who were on average 81.5 years old (56.8 % females).
      More than half (53.5 %) were assigned to care level I and 781 (14.1 %) were
      diagnosed with cancer. The study cohort received on average 7.8 different
      medications (with vs. without cancer: 8.6 vs. 7.6, respectively) and 43.8 % had
      prescriptions for analgesics (with vs. without cancer: 52.5 vs. 42.3 %,
      respectively). A total of 37.1 % were taking WHO step 1 analgesics (step 2: 11.4
      % and step 3: 9.2 %). The proportion of persons receiving metamizole (dipyrone)
      was 28.3 % (with vs. without cancer: 35.6 vs. 27.1 %, respectively). Regarding
      all prescriptions, metamizole was by far the most frequently prescribed
      medication in nursing homes followed by melperone and omeprazole. CONCLUSION:
      Approximately one third of nursing home residents received metamizole and most
      were long-term prescriptions. Considering that metamizole is associated with
      potentially life-threatening adverse effects, caution is indicated particularly
      when prescribed over long periods.

PMID- 25966867
TI  - Ethyl Cellulose and Cetrimonium Bromide Assisted Synthesis of Mesoporous, Hexagon
      Shaped ZnO Nanodisks with Exposed +/-{0001} Polar Facets for Enhanced
      Photovoltaic Performance in Quantum Dot Sensitized Solar Cells.
AB  - Hexagon shaped mesoporous zinc oxide nanodisks (ZnO NDs) with exposed +/-{0001}
      polar facets have been synthesized by using ethyl cellulose (EC) and cetrimonium
      bromide (CTAB) as the capping and structure directing agents. We have
      characterized ZnO NDs using analytical techniques, such as powder X-ray
      diffraction (PXRD), diffuse reflectance UV-visible (UV-vis) spectroscopy,
      photoluminescence (PL) spectroscopy, field emission scanning electron microscopy
      (FESEM), transmission electron microscopy (TEM), and Brunauer-Emmett-Teller (BET)
      surface area analysis and proposed a plausible mechanism for the formation of ZnO
      NDs. EC molecules form a colloidal solution in a 1-butanol:water (3:1) solvent
      system having a negative zeta potential (zeta ~ -32 mV) value which can inhibit
      CTAB assisted c-axis growth of ZnO crystal and encourage the formation of ZnO
      NDs. In the control reactions carried out in presence of only CTAB and only EC,
      formation of hexagonal ZnO nanorods (NRs) and ZnO nanosheets (NSs) composed of
      numerous ZnO nanoparticles are observed, respectively. Photovoltaic properties of
      ZnO NDs as compared to ZnO NRs, ZnO NSs, and conventional ZnO nanoparticles (NPs)
      are investigated by co-sensitizing with CdS/CdSe quantum dots (QDs). An ~35%
      increase in power conversion efficiency (PCE, eta) is observed in ZnO NDs (eta ~
      4.86%) as compared to ZnO NPs (eta ~ 3.14%) while the values of PCE for ZnO NR
      and ZnO NS based devices are found to be ~2.52% and ~1.64%, respectively.
      Enhanced photovoltaic performance of the ZnO NDs based solar cell is attributed
      to an efficient charge separation and collection, boosted by the exposed +/
      (0001) facets apart from the single crystalline nature, better light-scattering
      effects, and high BET surface area for sensitizer particle adsorption.
      Electrochemical impedance spectroscopy (EIS) analysis further reveals that the
      charge recombination resistance and photoinduced electron lifetime are
      substantially higher in the ZnO ND based device than in ZnO NR, ZnO NP, and ZnO
      NS based devices, which demonstrates a slower electron-hole (e(-)-h(+))
      recombination rate and faster charge migration through the single crystalline ZnO
      NDs. 

PMID- 25966866
TI  - Aluminium-phthalocyanine chloride nanoemulsions for anticancer photodynamic
      therapy: Development and in vitro activity against monolayers and spheroids of
      human mammary adenocarcinoma MCF-7 cells.
AB  - BACKGROUND: Photodynamic therapy (PDT) combines light, molecular oxygen and a
      photosensitizer to induce oxidative stress in target cells. Certain hydrophobic
      photosensitizers, such as aluminium-phthalocyanine chloride (AlPc), have
      significant potential for antitumor PDT applications. However, hydrophobic
      molecules often require drug-delivery systems, such as nanostructures, to improve
      their pharmacokinetic properties and to prevent aggregation, which has a
      quenching effect on the photoemission properties in aqueous media. As a result,
      this work aims to develop and test the efficacy of an AlPc in the form of a
      nanoemulsion to enable its use in anticancer PDT. RESULTS: The nanoemulsion was
      developed using castor oil and Cremophor ELP(r), and a monodisperse population of
      nanodroplets with a hydrodynamic diameter of approximately 25 nm was obtained.
      While free AlPc failed to show significant activity against human breast
      adenocarcinoma MCF-7 cells in an in vitro PDT assay, the AlPc in the nanoemulsion
      showed intense photodynamic activity. Photoactivated AlPc exhibited a 50 %
      cytotoxicity concentration (CC50) of 6.0 nM when applied to MCF-7 cell monolayers
      and exerted a powerful cytotoxic effect on MCF-7 cell spheroids. CONCLUSION:
      Through the use of spontaneous emulsification, a stable AlPc nanoemulsion was
      developed that exhibits strong in vitro photodynamic activity on cancer cells.

PMID- 25966868
TI  - New compound with DNA Topo I inhibitory activity purified from Penicillium
      oxalicum HSY05.
AB  - Strain HSY05 was isolated from sea sediment collected from the South China Sea
      and was later identified as Penicillium oxalicum by 16S rDNA sequence analysis.
      Various chromatographic processes led to the isolation and purification of two
      metabolites from the fermentation culture of HSY05, including one new compound,
      2,2',4,4'-tetrahyoxy-8'-methyl-6-methoxy-acyl-ethyl-diphenylmethanone (1), and a
      known compound secalonic acid D (SAD, 2), as characterised by UV, IR, 1D, 2D-NMR
      and MS data. The inhibitory activities against topoisomerase I of these two
      compounds were evaluated. The result showed that in addition to the known topo I
      inhibitor SAD (2), compound 1 also exhibited a moderate inhibitory effect. 

PMID- 25966869
TI  - Xylan-Degrading Catalytic Flagellar Nanorods.
AB  - Flagellin, the main component of flagellar filaments, is a protein possessing
      polymerization ability. In this work, a novel fusion construct of xylanase A from
      B. subtilis and Salmonella flagellin was created which is applicable to build
      xylan-degrading catalytic nanorods of high stability. The FliC-XynA chimera when
      overexpressed in a flagellin deficient Salmonella host strain was secreted into
      the culture medium by the flagellum-specific export machinery allowing easy
      purification. Filamentous assemblies displaying high surface density of catalytic
      sites were produced by ammonium sulfate-induced polymerization. FliC-XynA
      nanorods were resistant to proteolytic degradation and preserved their enzymatic
      activity for a long period of time. Furnishing enzymes with self-assembling
      ability to build catalytic nanorods offers a promising alternative approach to
      enzyme immobilization onto nanostructured synthetic scaffolds. 

PMID- 25966870
TI  - Computerized tomography-based predictive model for differentiation of Crohn's
      disease from intestinal tuberculosis.
AB  - BACKGROUND: Intestinal tuberculosis (ITB) and Crohn's disease (CD) have clinical,
      radiological, endoscopic, and histological resemblance. There is paucity of
      literature regarding differentiation of CD and ITB based on radiology using
      computed tomography (CT). AIMS: The present study was designed to compare CT
      features of ITB and CD and develop a predictive model to differentiate ITB and
      CD. METHODS: Patients with ITB and CD, who underwent CT enteroclysis/CT
      enterography/CT abdomen before starting treatment, were recruited. Specific
      findings were noted by a radiologist who was blinded to the diagnosis. A
      predictive model was developed based on the features which were significantly
      different in these diseases. RESULTS: Fifty-four patients with CD and 50 patients
      with ITB were compared. On univariate analysis, left colonic involvement,
      ileocecal involvement, long-segment involvement, comb sign, presence of skip
      lesions, involvement of >=3 segments and >=1-cm sized lymph nodes were
      significantly different between CD and ITB. On multivariate analysis, ileocecal
      involvement, long-segment involvement and the presence of lymph node >=1 cm were
      statistically significant. Based upon the latter three variables, a risk score
      (with values ranging from 0 to 3) was generated, with scores 0 and 1 having
      specificity of 100 % and 87 %, respectively, and positive predictive values (PPV)
      of 100 % and 76 %, respectively, for ITB and scores 2 and 3 having specificity of
      68 % and 90 %, respectively, and PPV of 63 % and 80 %, respectively, for CD.
      CONCLUSIONS: A predictive model based on the presence of long-segment
      involvement, ileocecal involvement and lymph nodes sized >=1 cm on CT could
      differentiate ITB and CD with good specificity and PPV.

PMID- 25966871
TI  - Gastrointestinal bleeding in a young man: think outside the box.

PMID- 25966872
TI  - Surface Modification of Poly(dimethylsiloxane) Using Ionic Complementary Peptides
      to Minimize Nonspecific Protein Adsorption.
AB  - Poly(dimethylsiloxane) (PDMS) has become a widely used material for microfluidic
      and biological applications. However, PDMS has unacceptably high levels of
      nonspecific protein adsorption, which significantly lowers the performance of
      PDMS-based microfluidic chips. Most existing methods to reduce protein fouling of
      PDMS are to make the surface more hydrophilic by surface oxidization, polymer
      grafting, and physisorbed coatings. These methods suffer from the relatively
      short-term stability, the multistep complex treatment procedure, or the
      insufficient adsorption reduction. Herein, we developed a novel and facile
      modification method based on self-assembled peptides with well-tailored amino
      acid composition and sequence, which can also interact strongly with the PDMS
      surface in the same way as proteins, for suppressing the nonspecific protein
      fouling and improving the biocompatibility of PDMS-based microfluidic chips. We
      first demonstrated that an ionic complementary peptide, EAR16-II with a sequence
      of [(Ala-Glu-Ala-Glu-Ala-Arg-Ala-Arg)2], can readily self-assemble into an
      amphipathic film predominantly composed of tightly packed beta-sheets on the
      native hydrophobic and plasma-oxidized hydrophilic PDMS surfaces upon low
      concentrations of carbohydrates. The self-assembled EAR16-II amphipathic film
      exposed its hydrophobic side to the solution and thus rendered the PDMS surface
      hydrophobic with water contact angles (WCAs) of around 110.0 degrees . However,
      the self-assembled EAR16-II amphipathic film exhibited excellent protein
      repelling and blood compatibility properties comparable to or better than those
      obtained with previously reported methods. A schematic model has been proposed to
      explain the interactions of EAR16-II with the PDMS surface and the antifouling
      capability of EAR16-II coatings at a molecular level. The current work will pave
      the way to the development of novel coating materials to address the nonspecific
      protein adsorption on PDMS, thereby broadening the potential uses of PDMS-based
      microfluidic chips in complex biological analysis. 

PMID- 25966873
TI  - Nanospray Drying Technology: Existing Limitations and Future Challenges.

PMID- 25966875
TI  - Label-free capacitance-based identification of viruses.
AB  - This study was undertaken to quantitate a single virus suspension in culture
      medium without any pre-processing. The electrical capacitance per virus particle
      was used to identify the kind of virus present by measuring the suspension (virus
      plus medium) capacitance, de-embedding the medium contribution, and dividing by
      the virus count. The proposed technique is based on finding the single virus
      effective dielectric constant which is directly related to the virus composition.
      This value was used to identify the virus type accordingly. Two types of viruses
      thus tested were further quantified by a biochemical technique to validate the
      results. Furthermore, non-organic nanoparticles with known concentration and
      capacitance per particle were identified using the proposed method. The
      selectivity of the method was demonstrated by performing electrical measurements
      on a third virus, revealing that the proposed technique is specific and sensitive
      enough to permit detection of a few hundred virus particles per milliliter within
      a few minutes. 

PMID- 25966874
TI  - Severe central and peripheral paraneoplastic demyelination associated with
      tumours of the ovaries.
AB  - PURPOSE: The aim of the study is to present MRI examinations of the brain and
      spinal cord, performed in girls with acute severe neurological presentation of
      paraneoplastic syndrome associated with ovarian teratomas. Paraneoplastic
      neurological syndrome (PNS) is a rare disorder caused by remote effects of
      malignancy in different organs. The pathogenesis of PNS concerns the autoimmune
      system and specific antibodies. PNS can be seen as encephalomyelitis, limbic
      encephalitis, progressive multifocal leukoencephalopathy, cerebellar ataxia,
      brainstem encephalitis, and paraneoplastic cerebellar degeneration. These
      symptoms are potentially reversible, if the underlying neoplasm is removed.
      METHODS: We presented three girls, aged 13, 17, and 18 years. They were all
      referred to the hospital because of an acute onset of severe disseminated
      encephalomyelitis. All MRI exams were performed on a 1.5 T scanner with a routine
      brain and spinal cord protocol, including TSE T2-WI and FLAIR sequences. In all
      cases, a contrast agent was injected in the standard dose. RESULTS: Neurological
      examination performed at the onset of the disease revealed hemiparesis, seizures,
      and consciousness disturbances. In one girl, visual field loss was also
      disclosed. They were all healthy before the onset of the disease. Brain and
      spinal cord MR imaging revealed multiple hyperintense lesions located
      supratentorially in the white matter of both hemispheres, in the pons,
      cerebellum, and spinal cord. Patients were treated with methyloprednisolone IV
      and IVIG. They all improved but significant sequelae were present. Two of them
      developed symptoms of acute demyelinating polyradiculoneuropathy within 2 months
      after the onset of encephalomyelitis. At the same time, brain MRI showed
      progression of the lesions. In two patients, anti-Yo antibodies were present in
      blood. Extensive examinations revealed bilateral ovarian teratomas in two
      patients, and left-sided ovarian teratoma in one case. Surgical resection of
      teratomas resulted in rapid clinical improvement. CONCLUSIONS: These cases show
      that in children and adolescents, acute demyelinating disease can be a
      manifestation of paraneoplastic neurological syndrome. Thus, PNS should always be
      considered in the differential diagnosis of encephalomyelitis. In female children
      and adolescents with suspected PNS, it is important to search for ovarian
      tumours.

PMID- 25966876
TI  - Method for Preparation and Electroporation of S. aureus and S. epidermidis.
AB  - For bacterial species that are not known to be naturally competent, such as
      Staphylococcus aureus and Staphylococcus epidermidis, electroporation is an
      efficient method for introducing genetic material into the cell. The technique
      utilizes electrical pulses to transiently permeabilize bacterial cell membranes,
      which allows for the passage of plasmid DNA across the membranes. Here, we
      describe methods for preparing electrocompetent S. aureus and S. epidermidis
      cells and outline a procedure for electroporation of the prepared competent
      cells.

PMID- 25966877
TI  - Nonlinear relationship between waist to hip ratio, weight and strength in elders:
      is gender the key?
AB  - Visceral fat has a high metabolic activity with deleterious effects on health
      contributing to the risk for the frailty syndrome. We studied the association
      between waist to hip ratio (an indirect measure of visceral fat stores) on upper
      and lower extremities strength. 1741 individuals aged >=65 participated in this
      study. The data was obtained from the Toledo Study for Healthy Aging. For each
      gender, we studied the relationship between the waist-to-hip ratio (WHR), body
      mass index (BMI) and regional muscle strength (grip, shoulder, knee and hip)
      using multivariate linear regression and kernel regression statistical models.
      WHR was higher in men than in women (0.98 +/- 0.07 vs. 0.91 +/- 0.08,
      respectively, P < 0.05). In women with high WHR, we observed a decrease in
      strength especially in those with a normal BMI. As the WHR lowered, the strength
      increased regardless of the BMI. In men, lower strength was generally related to
      the lowest and highest WHR's. Maximum strength in men corresponded at a WHR
      around 1 and the highest BMI. Muscle strength depends on the joined distribution
      of WHR and BMI according to gender. In consequence, sex, WHR and BMI should be
      analyzed conjointly to study the relationship among fat distribution, weight and
      muscle strength. 

PMID- 25966878
TI  - Spasmodic dysphonia follow-up with videolaryngoscopy and voice spectrography
      during treatment with botulinum toxin.
AB  - Spasmodic dysphonia (SD) is a focal dystonia of laryngeal muscles seriously
      impairing quality of voice. Adductor SD (ADSD) is the most common presentation of
      this disorder that can be identified by specialized phoniatricians and
      neurologists firstly on a clinical evaluation and then confirmed by
      videolaryngoscopy (VL). Botulinum toxin (BTX) injection with electromyographic
      guidance in muscles around vocal cords is the most effective treatment. Voice
      Handicap Index (VHI) questionnaire is the main tool to assess dysphonia and
      response to treatment. Objective of this study is to perform VL and voice
      spectrography (VS) to confirm the efficacy of BTX injections over time. 13
      patients with ADSD were studied with VHI, VL and VS before and after 4
      consecutive treatment with onobotulinumtoxin-A. For each treatment vocal
      improvement was proved by a significant reduction of VHI score and increase of
      maximum time phonation and harmonic-to-noise ratio while VL showed the absence of
      spasm in most of patients. No change of the response to BTX was found between
      injections. This study supports the efficacy of the treatment of SD with BTX with
      objective measurements and suggests that the efficacy of recurring treatments is
      stable over time.

PMID- 25966879
TI  - Assessment of heavy metals and metalloids in tissues of two frog species: Rana
      tigrina and Euphlyctis cyanophlyctis from industrial city Sialkot, Pakistan.
AB  - In the present study, we investigated the concentrations of Ni, Fe, Pb, Cu, Co,
      Zn, Cd, Mn, and Cr in selected body tissues (liver, stomach, kidney, heart,
      lungs, and skeletal muscles) of two frog species: Rana tigrina and Euphlyctis
      cyanophlyctis captured from industrial wastewater of Sialkot city known worldwide
      for its tanning industry. The both frog species had darker appearance,
      distinctively different wet body weight, and snout-vent length. The results
      revealed that the heavy metal concentrations were high in the samples collected
      from industrial sites as compared to non-industrial sites. The different tissues
      of R. tigrina and E. cyanophlyctis exhibited little significant differences from
      two sites. The concentrations of heavy metals were more in tissues of R. tigrina
      as compared to E. cyanophlyctis. Mean concentration of Cd, Fe, Ni, Mn, Cu, and Cr
      was comparatively greater in R. tigrina, whereas Pb and Co were higher in E.
      cyanophlyctis. The concentration of Cu and Cd in the liver and kidney were
      relatively more in both species as compared to other organs. Further, the results
      indicated that frogs collected from industrial sites showed decreased body length
      and weight, and greater metal accumulation. The results will help the authorities
      for the conservation of these frog species which are under the influence of heavy
      metal contamination. 

PMID- 25966880
TI  - Pre-hatching fluoxetine-induced neurochemical, neurodevelopmental, and
      immunological changes in newly hatched cuttlefish.
AB  - Embryonic and early postembryonic development of the cuttlefish Sepia officinalis
      (a cephalopod mollusk) occurs in coastal waters, an environment subject to
      considerable pressure from xenobiotic pollutants such as pharmaceutical residues.
      Given the role of serotonin in brain development and its interaction with
      neurodevelopmental functions, this study focused on fluoxetine (FLX), a selective
      serotonin reuptake inhibitor (SSRI, antidepressant). The goal was to determine
      the effects of subchronic waterborne FLX exposure (1 and 10 MUg L(-1)) during the
      last 15 days of embryonic development on neurochemical, neurodevelopmental,
      behavioral, and immunological endpoints at hatching. Our results showed for the
      first time that organic contaminants, such as FLX, could pass through the
      eggshell during embryonic development, leading to a substantial accumulation of
      this molecule in hatchlings. We also found that FLX embryonic exposure (1 and 10
      MUg L(-1)) (1) modulated dopaminergic but not serotonergic neurotransmission, (2)
      decreased cell proliferation in key brain structures for cognitive and visual
      processing, (3) did not induce a conspicuous change in camouflage quality, and
      (4) decreased lysozyme activity. In the long term, these alterations observed
      during a critical period of development may impair complex behaviors of the
      juvenile cuttlefish and thus lead to a decrease in their survival. Finally, we
      suggest a different mode of action by FLX between vertebrate and non-vertebrate
      species and raise questions regarding the vulnerability of early life stages of
      cuttlefish to the pharmaceutical contamination found in coastal waters.

PMID- 25966881
TI  - Chlorpyrifos-induced biomarkers in Japanese medaka (Oryzias latipes).
AB  - Chlorpyrifos (CHL) is an organophosphate compound that is widely used as an
      insecticide. Due to its repeated use and high environmental residual property,
      CHL is frequently passed into aquatic environments by runoff. Consequently, there
      may be an adverse effect on aquatic vertebrate animals, including fish.
      Therefore, in this study, we assessed how CHL affected Japanese medaka (Oryzias
      latipes). The acute toxicity of CHL in adult fish after 96 h of exposure was
      determined to be 212.50, 266.79, and 412.28 MUg L(-1) (LC25, LC50, and LC95,
      respectively). Acetylcholinesterase (AChE), glutathione S-transferase (GST), and
      carboxylesterase (CE) activities were obtained from the livers of dead or
      surviving fish, and the results showed 4.8-fold lower, 4.5-fold higher, and 18.6
      fold lower activities for the AChE, GST, and CE, respectively, for 64-h exposure
      at a concentration of 400 MUg L(-1) of CHL. In the embryo toxicity test, curved
      spines were observed in embryos that were exposed to CHL for 48 h in a
      concentration-dependent manner. With identification of biomarkers for CHL in the
      fish, two protein peaks, 5550.86 and 5639.79 m/z, were found to be upregulated.
      These two proteins can be used as protein biomarkers for CHL contamination in
      aquatic systems. A phosphatidyl choline with an m/z ratio of 556.32 dramatically
      decreased after CHL exposure in the fish; thus, it may be considered as a lipid
      biomarker for CHL. It is assumed as the first report to identify a phospholipid
      biomarker using a lipidomics approach in fish toxicology. Taken together, these
      results demonstrated the adverse effects of CHL on Japanese medaka and reveal
      several candidate biomarkers that can be used as diagnostic tools for determining
      CHL. 

PMID- 25966882
TI  - Dissipation of deltamethrin, triazophos, and endosulfan in ready mix formulations
      in tomato (Lycopersicon esculentum L.) and Egg plant (Solanum melongena L.).
AB  - Persistence of delltamethrin, endosulfan, and triazophos in egg plant and tomato
      was studied following application of two ready mix formulations of insecticides
      viz. deltametrhin and endosulfan (Cobra 5000; 0.75% deltamethrin + 29.5%
      endosulfan) and deltamethrin and triazophos (Annaconda Plus; 1% deltamethrin +
      35% triazophos) at recommended (1.0 L/ha and double dose 2.0 L/ha). The residues
      of deltamethrin persisted till 7 and 5 days in tomato and egg plant fruits,
      respectively, in the ready mix formulation of Cobra 5000 whereas endosulfan
      persisted till 15 and 10 days in tomato and egg plant fruits, respectively.
      Dissipation of the insecticides followed first-order kinetics with half-life
      values of deltamethrin and endosulfan ranged from 2.6 to 4.7 and 1.4 to 1.7 days,
      respectively, for both the vegetables. In case of combination mix of deltamethrin
      and triazophos (Annaconda Plus), deltamethrin persisted beyond 5 days in both
      tomato and egg plant fruits, while triazophos persisted till 10 days in both the
      vegetables. Residues of deltamethrin and triazophos dissipated with half-life of
      2.6-4.2 and 1.7-4.1 days, respectively, on tomato and egg plant fruits. Based on
      the Codex MRL limits, a safe waiting period of 5 and 3 days is suggested for
      tomato and egg plant, respectively, for the ready mix formulation of deltamethrin
      and endosulfan (Cobra 5000), and 5-day waiting period is suggested for tomato and
      egg plant for the combination mix of deltamethrin and triazophos.

PMID- 25966883
TI  - Temporal and spatial variations in phytoplankton: correlations with environmental
      factors in Shengjin Lake, China.
AB  - Temporal and spatial variations in the phytoplankton community and environmental
      variables were investigated from February to July 2014, in the upper lake of
      Shengjin Lake, China. We identified 192 species of phytoplankton belonging to 8
      phyla and 84 genera, of which 46.4% of Chlorophyta, 29.2% of Bacillariophyta, and
      12.5% of Cyanophyta. There were 14 predominant species. Marked temporal and
      spatial variations were observed in the phytoplankton community. The total
      abundance of phytoplankton ranged from 3.66 * 10(5) to 867.93 * 10(5) cells/L and
      total biomass ranging from 0.40 to 20.89 mg/L. The Shannon-Wiener diversity index
      varied from 3.50 to 8.35 with an average of 5.58, revealing high biodiversity in
      the phytoplankton community. There were substantial temporal changes in the
      dominant species, from Bacillariophyta and Cryptophyta to Cyanophyta and
      Chlorophyta. Phytoplankton biomass and abundance showed a similar increasing
      trend from February to July. Pearson correlations and Redundancy analysis
      revealed that the most significant environmental factors influencing
      phytoplankton community were water temperature (T), transparency (SD), and
      nutrient concentration. The positive correlation between the key water bird areas
      and phytoplankton biomass indicated that the droppings of wintering water birds
      had an important influence on the phytoplankton community in the upper lake of
      Shengjin Lake.

PMID- 25966885
TI  - Directing carbon nanotubes from aqueous phase to o/w interface for heavy metal
      uptaking.
AB  - Separation and reuse of dispersed nanoparticles are major obstacles to the
      extensive application of nano-sized absorbents in wastewater treatment. Herein,
      we demonstrate the capability of directing acid-oxidized carbon nanotubes (CNTs)
      as the transfer vehicles of heavy metal ions from simulated wastewater. The heavy
      metal-loaded CNTs can be readily separated from the aqueous phase via the
      aggregation process at an oil/water (o/w) interface. The minimum surfactant
      amount to achieve 99 % transfer ratio (Tr) of 100 mg/L CNTs from water phase to
      o/w interface was ~0.01 mM. The adsorption experiments showed that the removal
      efficiency of the divalent lead ions increased with an increase in CNT mass, and
      the subsequent addition of cetyltrimethylammonium bromide (CTAB) surfactant did
      not negatively impact the removal of soluble divalent lead species (Pb(II)). In a
      wide region of pH and ionic strength, both the decontamination of Pb(II) and the
      transfer of CNTs from water phase to o/w interface can be accomplished
      successively. The method presented in this study may be developed as a generic
      one for collecting or recycling the pollutant-loaded nano-sized absorbents.

PMID- 25966884
TI  - Inhibition of residual n-hexane in anaerobic digestion of lipid-extracted
      microalgal wastes and microbial community shift.
AB  - Converting lipid-extracted microalgal wastes to methane (CH4) via anaerobic
      digestion (AD) has the potential to make microalgae-based biodiesel platform more
      sustainable. However, it is apparent that remaining n-hexane (C6H14) from lipid
      extraction could inhibit metabolic pathway of methanogens. To test an inhibitory
      influence of residual n-hexane, this study conducted a series of batch AD by
      mixing lipid-extracted Chlorella vulgaris with a wide range of n-hexane
      concentration (~10 g chemical oxygen demand (COD)/L). Experimental results show
      that the inhibition of n-hexane on CH4 yield was negligible up to 2 g COD/L and
      inhibition to methanogenesis became significant when it was higher than 4 g COD/L
      based on quantitative mass balance. Inhibition threshold was about 4 g COD/L of n
      hexane. Analytical result of microbial community profile revealed that dominance
      of alkane-degrading sulfate-reducing bacteria (SRB) and syntrophic bacteria
      increased, while that of methanogens sharply dropped as n-hexane concentration
      increased. These findings offer a useful guideline of threshold n-hexane
      concentration and microbial community shift for the AD of lipid-extracted
      microalgal wastes. 

PMID- 25966886
TI  - Characterization of carbonaceous aerosols at Mount Lu in South China: implication
      for secondary organic carbon formation and long-range transport.
AB  - In order to understand the sources and potential formation processes of
      atmospheric carbonaceous aerosols in South China, fine particle samples were
      collected at a high-elevation mountain site--Mount Lu (29 degrees 35' N, 115
      degrees 59' E, 1165 m A.S.L.) during August-September, 2011. Eight carbonaceous
      fractions from particles were resolved following the IMPROVE thermal/optical
      reflectance protocol. During the observation campaign, the daily concentrations
      of PM2.5 at Mount Lu ranged from 7.69 to 116.39 MUg/m(3), with an average of
      58.76 MUg/m(3). The observed average organic carbon (OC) and elemental carbon
      (EC) concentrations in PM2.5 were 3.78 and 1.28 MUg/m(3), respectively. Secondary
      organic carbon (SOC) concentration, estimated by EC-tracer method, was 2.07
      MUg/m(3) on average, accounting for 45.0% of the total OC. The enhancement of
      secondary organic aerosol (SOA) formation was observed during cloud/fog
      processing, and heterogeneous acid-catalyzed reactions may have contributed to
      SOA formation as well. Back trajectory analysis indicated that air masses were
      mainly sourced from southern China during observation period, and this air mass
      source was featured by highest values of OC and effective carbon ratio (ECR).
      Relation of carbonaceous species and principal component analysis indicated that
      multiple sources contributed to the carbonaceous aerosols at Mount Lu.

PMID- 25966887
TI  - Lycopersicon esculentum under low temperature stress: an approach toward enhanced
      antioxidants and yield.
AB  - Brassinosteroids (BRs) have been implicated to overcome various abiotic stresses,
      and low temperature stress poses a serious threat to productivity of various
      horticultural crops like tomato. Therefore, a study was conducted to unravel the
      possible role of BRs in conferring alleviation to low temperature stress in
      Lycopersicon esculentum. Twenty-day-old seedlings of tomato var. S-22 (chilling
      tolerant) and PKM-1 (chilling sensitive) were sown in earthen pots, and at 40
      days stage of growth, plants were exposed to varied levels of low temperatures
      (10/3, 12/7, 20/14, or 25/18  degrees C) for 24 h in a growth chamber. At 50 days
      stage of growth, the foliage of plants were sprayed with 0 or 10(-8) M of BRs (28
      homobrassinolide or 24-epibrassinolide), and 60-day-old plants were harvested to
      assess various physiological and biochemical parameters. Low temperatures induced
      a significant reduction in growth traits, chlorophyll content, and rate of
      photosynthesis in both the varieties differentially. Activities of antioxidant
      enzymes (catalase, peroxidase, and superoxide dismutase) and leaf proline content
      also increased substantially in both the varieties with decreasing temperature.
      On the other hand, treatment of BRs under stress and stress-free conditions
      significantly increased the aforesaid growth traits and biochemical parameters.
      Moreover, BRs further accelerated the antioxidative enzymes and proline content,
      which were already enhanced by the low temperature stress. Out of the two
      analogues of BRs tested, 24-epibrassinolide (EBL) was found more effective for
      both the varieties of tomato. EBL was found more potent stress alleviator against
      low temperature in both varieties of tomato. 

PMID- 25966888
TI  - The lasting effect of limonene-induced particle formation on air quality in a
      genuine indoor environment.
AB  - Atmospheric ozone-terpene reactions, which form secondary organic aerosol (SOA)
      particles, can affect indoor air quality when outdoor air mixes with indoor air
      during ventilation. This study, conducted in Leipzig, Germany, focused on
      limonene-induced particle formation in a genuine indoor environment (24 m(3)).
      Particle number, limonene and ozone concentrations were monitored during the
      whole experimental period. After manual ventilation for 30 min, during which
      indoor ozone levels reached up to 22.7 ppb, limonene was introduced into the room
      at concentrations of approximately 180 to 250 MUg m(-3). We observed strong
      particle formation and growth within a diameter range of 9 to 50 nm under real
      room conditions. Larger particles with diameters above 100 nm were less affected
      by limonene introduction. The total particle number concentrations (TPNCs) after
      limonene introduction clearly exceed outdoor values by a factor of 4.5 to 41
      reaching maximum concentrations of up to 267,000 particles cm(-3). The formation
      strength was influenced by background particles, which attenuated the formation
      of new SOA with increasing concentration, and by ozone levels, an increase of
      which by 10 ppb will result in a six times higher TPNC. This study emphasizes
      indoor environments to be preferred locations for particle formation and growth
      after ventilation events. As a consequence, SOA formation can produce
      significantly higher amounts of particles than transported by ventilation into
      the indoor air. 

PMID- 25966889
TI  - An open-source software package for multivariate modeling and clustering:
      applications to air quality management.
AB  - This paper presents an open-source software package, rSCA, which is developed
      based upon a stepwise cluster analysis method and serves as a statistical tool
      for modeling the relationships between multiple dependent and independent
      variables. The rSCA package is efficient in dealing with both continuous and
      discrete variables, as well as nonlinear relationships between the variables. It
      divides the sample sets of dependent variables into different subsets (or
      subclusters) through a series of cutting and merging operations based upon the
      theory of multivariate analysis of variance (MANOVA). The modeling results are
      given by a cluster tree, which includes both intermediate and leaf subclusters as
      well as the flow paths from the root of the tree to each leaf subcluster
      specified by a series of cutting and merging actions. The rSCA package is a handy
      and easy-to-use tool and is freely available at http://cran.r
      project.org/package=rSCA . By applying the developed package to air quality
      management in an urban environment, we demonstrate its effectiveness in dealing
      with the complicated relationships among multiple variables in real-world
      problems. 

PMID- 25966891
TI  - Unexpected action of lanthanum carbonate.

PMID- 25966890
TI  - Association between blood arsenic levels and nasal polyposis disease risk in the
      Tunisian population.
AB  - Although the pathophysiology underlying nasal polyposis (NP) formation is not
      fully understood, systemic, local, and environmental factors appear to contribute
      to NP disease development. This study aimed to explore the relationship between
      metal blood levels and NP risk. To the best of our knowledge, the current
      research represents the first scientific contribution reporting levels of Cr and
      As in blood of NP patients. In this context, 90 NP patients and 171 controls were
      recruited and blood samples were analyzed to determine the concentrations of As
      and Cr. Metal blood levels of As in patients (2.1 MUg/L) were significantly
      higher than those of controls (1.2 MUg/L). However, no significant difference in
      blood Cr levels was found between cases and controls. Arsenic blood levels of
      cigarette smokers were significantly higher than those of non-smokers.
      Environmental exposure and shisha consumption presented the most significant
      association with NP disease (OR = 10.1 and 14.1, respectively). High levels of
      blood As were significantly associated with NP disease (OR = 2.1). Cr blood
      levels were found to be associated with the four stages of polyps in both nasal
      cavities. This study found a strong association between nasal polyposis disease
      and As blood levels. These findings merit further investigation. 

PMID- 25966893
TI  - When all else fails: take a deep breath, meditate, and assume padmasana.

PMID- 25966894
TI  - Comparison of different fertilisation media for an in vitro
      maturation?fertilisation?culture system using flow-cytometrically sorted X
      chromosome-bearing spermatozoa for bovine embryo production.
AB  - High demand exists among commercial cattle producers for in vitro-derived bovine
      embryos fertilised with female sex-sorted spermatozoa from high-value breeding
      stock. The aim of this study was to evaluate three fertilisation media, namely
      M199, synthetic oviductal fluid (SOF) and Tyrode's albumin-lactate-pyruvate
      (TALP), on IVF performance using female sex-sorted spermatozoa. In all, 1143,
      1220 and 1041 cumulus-oocyte complexes were fertilised in M199, SOF and TALP,
      respectively. There were significant differences among fertilisation media (P <
      0.05) in cleavage rate (M199 = 57%, SOF = 71% and TALP = 72%), blastocyst
      formation (M199 = 9%, SOF = 20% and TALP = 19%), proportion of Grade 1
      blastocysts (M199 = 15%, SOF = 52% and TALP = 51%), proportion of Grade 3
      blastocysts (M199 = 58%, SOF = 21% and TALP = 20%) and hatching rates (M199 =
      29%, SOF = 60% and TALP = 65%). The inner cell mass (ICM) and trophectoderm (TE)
      cells of Day 7 blastocysts were also affected by the fertilisation medium.
      Embryos derived from SOF and TALP fertilisation media had higher numbers of ICM,
      TE and total cells than those fertilised in M199. In conclusion, fertilisation
      media affected cleavage rate, as well as subsequent embryo development, quality
      and hatching ability. SOF and TALP fertilisation media produced significantly
      more embryos of higher quality than M199.

PMID- 25966892
TI  - A survey of outcomes and management of patients post fragility fractures in
      China.
AB  - We found that the fragility hip and vertebral fractures caused excess mortality
      rates in this Chinese female population, which was unexpectedly lower than those
      in western countries and other Asian countries. This was the first nationwide
      survey relating to post-fracture outcomes conducted among Chinese population in
      Mainland China. INTRODUCTION: This study aimed to investigate the mortality, self
      care ability, diagnosis, and medication treatment of osteoporosis following
      fragility hip and vertebral fractures through a nationwide survey among female
      patients aged over 50 in Mainland China. METHODS: This was a multicenter,
      retrospective cohort study based on medical chart review and patient
      questionnaire. Female patients aged 50 or older admitted for low-trauma hip or
      vertebral fractures and discharged from Jan 1, 2008 to Dec 31, 2012 were
      followed. RESULTS: Total of 1151 subjects of hip fracture and 842 subjects of
      vertebral fracture were included. The mean age was 73.4 +/- 10.0, and the median
      of duration from index fracture to interview was 2.6 years. The overall 1-year, 2
      year, 3-year, 4-year, and 5-year cumulative mortality rates were 3.5, 7.0, 11.2,
      13.1, and 16.9 %, respectively. The first year mortality rates in hip (3.8 %, 95%
      CI 3.3-4.4 %) and vertebral fracture (3.1 %, 95% CI 2.5-3.7 %) were significantly
      higher than that in the general population (1.6 %). Impaired self-care ability
      was observed in 33.2, 40.6, and 23.8 % of overall, hip fracture, and vertebral
      fracture group, respectively. The overall diagnosis rate of osteoporosis was 56.8
      %, and bone mineral density (BMD) measurement had never been conducted in 42.0 %
      among these women. After the index fracture, 69.6 % of them received supplements
      and/or anti-osteoporotic medications, among which 39.6 % only received calcium
      with/without vitamin D supplementation. CONCLUSIONS: The osteoporotic hip and
      vertebral fractures caused excess mortality rates in this population of Mainland
      China. The current diagnosis and medical treatment following the fragility
      fractures is still insufficient in Mainland China.

PMID- 25966895
TI  - Trail making task performance in inpatients with anorexia nervosa and bulimia
      nervosa.
AB  - Set-shifting inefficiencies have been consistently identified in adults with
      anorexia nervosa (AN). It is less clear to what degree similar inefficiencies are
      present in those with bulimia nervosa (BN). It is also unknown whether
      perfectionism is related to set-shifting performance. We employed a commonly used
      set-shifting measure, the Trail Making Test (TMT), to compare the performance of
      inpatients with AN and BN with a healthy control sample. We also investigated
      whether perfectionism predicted TMT scores. Only the BN sample showed
      significantly suboptimal performance, while the AN sample was indistinguishable
      from controls on all measures. There were no differences between the AN subtypes
      (restrictive or binge/purge), but group sizes were small. Higher personal
      standards perfectionism was associated with better TMT scores across groups.
      Higher concern over mistakes perfectionism predicted better accuracy in the BN
      sample. Further research into the set-shifting profile of individuals with BN or
      binge/purge behaviours is needed.

PMID- 25966896
TI  - Pacing Postconditioning: Recent Insights of Mechanism of Action and Probable
      Future Clinical Application.
AB  - Ischemic heart disease, also known as coronary heart disease or coronary artery
      disease, accounts for >50% of cardiovascular events and is a leading cause
      worldwide of morbidity and mortality. Hypoperfusion of the heart is the major
      cause of injury in ischemic heart disease, as it results in the death of
      cardiomyoctes due to a lack of oxygen and energy. This injury ultimately leads to
      a dead area in the heart called infarcted area or myocardial infarction. The
      formation of myocardial infarction leads to a lengthy process of remodeling which
      causes many changes in the architecture and the electrophysiology of the heart.
      These changes may eventually lead to death due to arrhythmia or heart failure.
      Tremendous efforts have been made over the last decades to decrease the burden of
      ischemic reperfusion (I/R) injury. The first salvage to the ischemic heart is
      reperfusion; however, this procedure is associated with a subsequent reperfusion
      injury. In the 1980s, a method known as preconditioning was introduced and showed
      great potential in combating ischemic heart disease, but this technique is
      limited by the difficulty of its translation to the clinic as it requires the
      anticipation of an occurrence of ischemic heart disease. Not long after, a new
      method, postconditioning, was introduced. This method showed great success, and
      several studies were performed to investigate its signaling cascades and the
      possibility of its translation to the clinic. Thereafter, several trials were
      made, and many methods of postconditioning were developed. One of these is
      intermittent dyssynchrony, pacing postconditioning (PPC), of the heart, which
      involves brief episodes of electrical pacing. PPC afforded a pronounced
      protection to the heart against I/R injury, similar to that afforded by pre- and
      postconditioning. 

PMID- 25966897
TI  - Regional variation of chronic kidney disease in Germany: results from two
      population-based surveys.
AB  - BACKGROUND/AIMS: Due to the increasing prevalence of risk factors for chronic
      kidney disease (CKD), kidney dysfunction becomes a major public health problem.
      We investigated the CKD prevalence and determined to what extent the variation of
      risk factors explains the different CKD prevalence in Germany. METHODS: We
      analyzed data from 6,054 participants, aged 31 to 82 years, from the Study of
      Health in Pomerania (SHIP-1) in Northeast Germany and the Cooperative Health
      Research in the Region of Augsburg (KORA F4) Study in Southern Germany. Regional
      differences in selected percentiles corresponding to the cutpoints for estimated
      glomerular filtration rate (eGFR, <60 ml/min per 1.73 m(2)) and albumin-to
      creatinine ratio (ACR, >=30 mg/g) were tested using quantile regression models
      that adjusted for CKD risk factors. RESULTS: The prevalence of decreased
      eGFRcreatinine-cystatinC (5.9 vs. 3.1 %, p <0.001) and albuminuria (20.2 vs. 8.8
      %, p<0.001) were higher in SHIP-1 than in KORA F4. The differential distribution
      of risk factors explained 18-21% of the regional differences of decreased
      eGFRcreatinine-cystatinC and high ACR. CONCLUSIONS: The CKD prevalence is higher
      in Northeast than in Southern Germany. Differences in the prevalence of risk
      factors partly explain the higher disease burden of CKD in Northeast than in
      Southern Germany.

PMID- 25966899
TI  - Revisiting Chaos Theorem to Understand the Nature of miRNAs in Response to Drugs
      of Abuse.
AB  - Just like Matryoshka dolls, biological systems follow a hierarchical order that
      is based on dynamic bidirectional communication among its components. In addition
      to the convoluted inter-relationships, the complexity of each component spans
      several folds. Therefore, it becomes rather challenging to investigate phenotypes
      resulting from these networks as it requires the integration of reductionistic
      and holistic approaches. One dynamic system is the transcriptome which comprises
      a variety of RNA species. Some, like microRNAs, have recently received a lot of
      attention. miRNAs are very pleiotropic and have been considered as therapeutic
      and diagnostic candidates in the biomedical fields. In this review, we survey
      miRNA profiles in response to drugs of abuse (DA) using 118 studies. After
      providing a summary of miRNAs related to substance use disorders (SUD), general
      patterns of miRNA signatures are compared among studies for single or multiple
      drugs of abuse. Then, current challenges and drawbacks in the field are
      discussed. Finally, we provide support for considering miRNAs as a chaotic system
      in normal versus disrupted states particularly in SUD and propose an integrative
      approach for studying and analyzing miRNA data.

PMID- 25966898
TI  - Advanced analyses of kinetic stabilities of iggs modified by mutations and
      glycosylation.
AB  - The stability of Immunoglobulin G (IgG) affects production, storage and
      usability, especially in the clinic. The complex thermal and isothermal
      transitions of IgGs, especially their irreversibilities, pose a challenge to the
      proper determination of parameters describing their thermodynamic and kinetic
      stability. Here, we present a reliable mathematical model to study the
      irreversible thermal denaturations of antibody variants. The model was applied to
      two unrelated IgGs and their variants with stabilizing mutations as well as
      corresponding non-glycosylated forms of IgGs and Fab fragments. Thermal
      denaturations of IgGs were analyzed with three transitions, one reversible
      transition corresponding to C(H)2 domain unfolding followed by two consecutive
      irreversible transitions corresponding to Fab and C(H)3 domains, respectively.
      The parameters obtained allowed us to examine the effects of these mutations on
      the stabilities of individual domains within the full-length IgG. We found that
      the kinetic stability of the individual Fab fragment is significantly lowered
      within the IgG context, possibly because of intramolecular aggregation upon
      heating, while the stabilizing mutations have an especially beneficial effect.
      Thermal denaturations of non-glycosylated variants of IgG consist of more than
      three transitions and could not be analyzed by our model. However, isothermal
      denaturations demonstrated that the lack of glycosylation affects the stability
      of all and not just of the C(H)2 domain, suggesting that the partially unfolded
      domains may interact with each other during unfolding. Investigating thermal
      denaturation of IgGs according to our model provides a valuable tool for
      detecting subtle changes in thermodynamic and/or kinetic stabilities of
      individual domains.

PMID- 25966900
TI  - Cognitive impairment is not a predictor of failure to adhere to anticoagulation
      of stroke patients with atrial fibrillation.
AB  - BACKGROUND: Oral anticoagulation (OAC) with vitamin K antagonists (VKA) or direct
      oral anticoagulants (DOAC) is an effective strategy that is used for stroke
      prevention in patients with atrial fibrillation (AF). However, OAC is underused
      particularly in elderly patients, who are often physically disabled or
      cognitively impaired. We aimed at evaluating the effect of cognitive status and
      disability on OAC adherence 1 year after stroke or TIA. METHODS: In this
      prospective, single-center, observational study patients with ischemic stroke or
      TIA were consecutively included between 3/2011 and 9/2012. The detailed medical
      history, basic demographic variables, cardiovascular risk factors, stroke
      severity according to the National Institutes of Health Stroke Scale (NIHSS),
      medication including OAC were all recorded. Cognitive performance was measured
      using the Montreal Cognitive Assessment (MoCA) score at baseline. The functional
      status was assessed by recording activities and instrumental activities of daily
      living, respectively (ADL, IADL). After 12 months, patients had a follow-up visit
      to reassess the cognitive and functional status (MoCA, ADL and IADL) and to
      document the current use of OAC. RESULTS: In total, 12 months after the ischemic
      stroke or TIA AF had been diagnosed in 160/586 (27.3%). Of these, 151 patients
      (94.4%) were treated with OAC. OAC was performed using VKA in 79/151 (52.3%) and
      DOACs in 72/151 (47.7%). Cognitive impairment at 12 months follow-up was not
      associated with the absence of OAC treatment. However, regression analysis
      revealed that patients with AF with physical (ADL) and functional disability
      (IADL) were less likely to be treated with OAC (p = 0.08 and p = 0.04,
      respectively) 12 months after a stroke. None of these two factors, however, was
      independently associated with nonadherence to OAC 12 months after stroke.
      Although cognitive performance was similar in patients receiving VKA and direct
      anticoagulants (DOAC), adherence to VKA tended to be lower (82.6 vs. 94.6%, p =
      0.12). CONCLUSIONS: In stroke and TIA patients with AF, the multifactorial
      medical and functional constellation rather than cognitive impairment
      specifically can be an obstacle for long-term OAC.

PMID- 25966901
TI  - Titanium trisulfide monolayer: theoretical prediction of a new direct-gap
      semiconductor with high and anisotropic carrier mobility.
AB  - A new two-dimensional (2D) layered material, namely, titanium trisulfide (TiS3 )
      monolayer, is predicted to possess novel electronic properties. Ab initio
      calculations show that the perfect TiS3 monolayer is a direct-gap semiconductor
      with a bandgap of 1.02 eV, close to that of bulk silicon, and with high carrier
      mobility. More remarkably, the in-plane electron mobility of the 2D TiS3 is
      highly anisotropic, amounting to about 10 000 cm(2)  V(-1)  s(-1) in the b
      direction, which is higher than that of the MoS2 monolayer, whereas the hole
      mobility is about two orders of magnitude lower. Furthermore, TiS3 possesses
      lower cleavage energy than graphite, suggesting easy exfoliation for TiS3 . Both
      dynamical and thermal stability of the TiS3 monolayer is examined by phonon
      spectrum calculation and Born-Oppenheimer molecular dynamics simulation. The
      desired electronic properties render the TiS3 monolayer a promising 2D atomic
      layer material for applications in future nanoelectronics. 

PMID- 25966902
TI  - Human Dental Pulp Stem Cells Differentiate into Oligodendrocyte Progenitors Using
      the Expression of Olig2 Transcription Factor.
AB  - The helix-loop-helix transcription factor Olig2 is essential for lineage
      determination of oligodendrocytes. Differentiation of stem cells into
      oligodendrocytes and transplanting them is a novel strategy for the repair of
      different demyelination diseases. Dental pulp stem cells (DPSCs) are of great
      interest in regenerative medicine due to their potential for repairing damaged
      tissues. In this study, DPSCs were isolated from human third molars and
      transfected with the human Olig2 gene as a differentiation inducer for the
      oligodendrogenic pathway. Following the differentiation procedure, the expression
      of Sox2, NG2, PDGFRalpha, Nestin, MBP, Olig2, Oct4, glial fibrillary acidic
      protein and A2B5 as stage-specific markers was studied by real-time RT-qPCR,
      immunocytochemistry and Western blot analysis. The cells were transplanted into a
      mouse model of local sciatic damage by lysolecithin as a model for demyelination.
      Oligodendrocyte progenitor cells (OPCs) actively remyelinated and recovered the
      lysolecithin-induced damages in the sciatic nerve as revealed by treadmill
      exercise, the von Frey filament test and hind paw withdrawal in response to a
      thermal stimulus. Recovery of behavioral reflexes occurred 2-6 weeks after OPC
      transplantation. The results demonstrate that the expression of Olig2 in DPSCs
      reduces the expression of stem cell markers and induces the development of
      oligodendrocyte progenitors as revealed by the emergence of oligodendrocyte
      markers. DPSCs could be programmed into oligodendrocyte progenitors and
      considered as a simple and valuable source for the cell therapy of
      neurodegenerative diseases.

PMID- 25966903
TI  - Effectiveness and Organization of Addiction Medicine Training Across the Globe.
AB  - BACKGROUND: Over the past decade, addiction medicine training curricula have been
      developed to prepare physicians to work with substance use disorder patients.
      This review paper aimed at (1) summarizing scientific publications that outline
      the content of addiction medicine curricula and (2) evaluating the evidence for
      efficacy for training in addiction medicine. METHODS: We carried out a literature
      search on articles about addiction medicine training initiatives across the
      world, using PubMed, PsychINFO and EMBASE with the following search terms
      'substance abuse, addiction medicine, education and training.' RESULTS: We found
      29 articles on addiction medicine curricula at various academic levels. Nine
      studies reported on the need for addiction medicine training, 9 described
      addiction medicine curricula at various academic levels, and 11 described
      efficacy on addiction medicine curricula. CONCLUSIONS: Several key competences in
      addiction medicine were identified. Efficacy studies show that even short
      addiction medicine training programs can be effective in improving knowledge,
      skills and attitudes related to addiction medicine. A more uniform approach to
      addiction medicine training in terms of content and accreditation is discussed.

PMID- 25966906
TI  - The structure and stability of reduced and oxidized mononuclear platinum species
      on nanostructured ceria from density functional modeling.
AB  - We report our results for the structure and relative stability of mononuclear
      platinum species on a ceria nanoparticle Ce21O42 depending on reduction or
      oxidation of the system. The most stable platinum species is Pt(2+) at small
      {100} facets, where the ion is coordinated in a square-planar complex with four
      oxygen anions as ligands. Partial reduction of the system does not affect the
      state of platinum in this position but causes reduction of cerium ions. Atomic
      platinum species in all other modeled positions on the surface of the ceria
      nanoparticle are found to be in the oxidation state 0. Based on the calculated
      thermodynamic quantities we analyzed the formation of a preferable type of
      platinum species depending on the temperature and O2 pressure. Our thermodynamic
      model shows that the most stable species under standard conditions is PtO, while
      at the partial pressure of O2 below 100 Pa the stoichiometric complex Pt-Ce21O42
      is formed. In both structures there is Pt(2+) located in a square-planar complex.
      The characteristics of these two structures fit well the available EXAFS and XPS
      data. These structures are energetically stable with respect to sintering, while
      the agglomeration to platinum clusters is exothermic for the neutral mononuclear
      Pt species located at {111} facets. 

PMID- 25966905
TI  - Perioperative Management of Dabigatran: A Prospective Cohort Study.
AB  - BACKGROUND: The perioperative management of dabigatran in clinical practice is
      heterogeneous. We performed this study to evaluate the safety of perioperative
      management of dabigatran using a specified protocol. METHODS AND RESULTS:
      Patients treated with dabigatran and planned for an invasive procedure were
      eligible for inclusion. The timing of the last dose of dabigatran before the
      procedure was based on the creatinine clearance and procedure-related bleeding
      risk. Resumption of dabigatran was prespecified according to the complexity of
      the surgery and consequences of a bleeding complication. Patients were followed
      up for 30 days for major bleeding (primary outcome), minor bleeding, arterial
      thromboembolism, and death. We included 541 cases: 324 procedures (60%) with
      standard risk of bleeding and 217 procedures (40%) with increased risk of
      bleeding. The last dose of dabigatran was at 24, 48, or 96 hours before surgery
      according to the protocol in 46%, 37%, and 6%, respectively, of the patients.
      Resumption was timed according to protocol in 77% with 75 mg as the first dose on
      the day of procedure in 40% of the patients. Ten patients (1.8%; 95% confidence
      interval, 0.7-3.0) had major bleeding, and 28 patients (5.2%; 95% confidence
      interval, 3.3-7.0) had minor bleeding events. The only thromboembolic
      complication was transient ischemic attack in 1 patient (0.2%; 95% confidence
      interval, 0-0.5), and there were 4 deaths unrelated to bleeding or thrombosis.
      Bridging was not used preoperatively but was administered in 9 patients (1.7%)
      postoperatively. CONCLUSION: Our protocol for perioperative management of
      dabigatran appears to be effective and feasible.

PMID- 25966904
TI  - Synergistic control of sex hormones by 17beta-HSD type 7: a novel target for
      estrogen-dependent breast cancer.
AB  - 17beta-hydroxysteroid dehydrogenase (17beta-HSD) type 1 is known as a critical
      target to block the final step of estrogen production in estrogen-dependent
      breast cancer. Recent confirmation of the role of dyhydroxytestosterone (DHT) in
      counteracting estrogen-induced cell growth prompted us to study the reductive
      17beta-HSD type 7 (17beta-HSD7), which activates estrone while markedly
      inactivating DHT. The role of DHT in breast cancer cell proliferation is
      demonstrated by its independent suppression of cell growth in the presence of a
      physiological concentration of estradiol (E2). Moreover, an integral analysis of
      a large number of clinical samples in Oncomine datasets demonstrated the
      overexpression of 17beta-HSD7 in breast carcinoma. Inhibition of 17beta-HSD7 in
      breast cancer cells resulted in a lower level of E2 and a higher level of DHT,
      successively induced regulation of cyclinD1, p21, Bcl-2, and Bik, consequently
      arrested cell cycle in the G(0)/G(1) phase, and triggered apoptosis and auto
      downregulation feedback of the enzyme. Such inhibition led to significant
      shrinkage of xenograft tumors with decreased cancer cell density and reduced
      17beta-HSD7 expression. Decreased plasma E2 and elevated plasma DHT levels were
      also found. Thus, the dual functional 17beta-HSD7 is proposed as a novel target
      for estrogen-dependent breast cancer by regulating the balance of E2 and DHT.
      This demonstrates a conceptual advance on the general belief that the major role
      of this enzyme is in cholesterol metabolism.

PMID- 25966907
TI  - 3D genome architecture from populations to single cells.
AB  - Dominated by microscopy for decades the nuclear genome organization field has
      recently undergone a dramatic transition fuelled by new next generation
      sequencing technologies that are beginning to bridge the gap between microscopic
      observations and molecular scale studies. It is no longer in doubt that the
      nucleus is spatially compartmentalized and that the genome organization with
      respect to these compartments is cell type specific. However, it is still unclear
      if and how this organization contributes to genome function, or whether it is
      simply a consequence of it. This uncertainty is partly due to the cell-to-cell
      variability of genome organization, but also due to limitations of the
      measurement techniques and the scale of the problem at hand. Here we discuss some
      of the exciting recent progress made towards understanding three-dimensional
      genome architecture and function. 

PMID- 25966908
TI  - Balancing up and downregulation of the C. elegans X chromosomes.
AB  - In Caenorhabditis elegans, males have one X chromosome and hermaphrodites have
      two. Emerging evidence indicates that the male X is transcriptionally more active
      than autosomes to balance the single X to two sets of autosomes. Because
      upregulation is not limited to males, hermaphrodites need to strike back and
      downregulate expression from the two X chromosomes to balance gene expression in
      their genome. Hermaphrodite-specific downregulation involves binding of the
      dosage compensation complex to both Xs. Advances in recent years revealed that
      the action of the dosage compensation complex results in compaction of the X
      chromosomes, changes in the distribution of histone modifications, and ultimately
      limiting RNA Polymerase II loading to achieve chromosome-wide gene repression. 

PMID- 25966909
TI  - Influence of hydrofluoric acid concentration on the flexural strength of a
      feldspathic ceramic.
AB  - This study evaluated the effects of etching with increasing hydrofluoric (HF)
      acid concentrations on the roughness and flexural strength of a feldspathic
      ceramic. One hundred and fifty ceramic specimens (14*4*1.2 mm(2)) were produced
      from ceramic blocks (VitaBlocks Mark II). All specimens were polished, chamfered
      and sonically cleaned in isopropyl alcohol. Specimens were randomly divided into
      5 groups (n=30): SC (control) no ceramic surface etching; HF1, HF3, HF5 and HF10
      ceramic surface etching for 60s with 1%, 3%, 5% and 10% HF acid concentrations,
      respectively. Profilometry was performed in all specimens to evaluate roughness
      prior to flexural strength testing. Data were analyzed using one-way ANOVA and
      Tukey's test (alpha=0.05). Weibull module (m) and characteristic stress (sigmac)
      were also determined. HF acid etching, regardless of the concentration used, led
      to significantly rougher surfaces than the control (p<0.05). However, the mean
      flexural strength values were not statistically different among the etched groups
      (106.47 to 102.02 MPa). Acid etching significantly reduced the mean flexural
      strength when compared with the control (143.3 MPa). Weibull modulus of the
      groups was similar, except for the HF5 group that was higher compared to HF3.
      Flexural strength was similarly affected by the different HF acid concentrations
      tested, but roughness increased higher the acid concentration. Ceramic etching
      led to a significant reduction in strength when compared to the untreated
      ceramic, regardless of its concentration.

PMID- 25966910
TI  - Defining health and disease: setting the boundaries for physiotherapy. Are we
      undertreating or overtreating? How can we tell?

PMID- 25966911
TI  - The impact of physical activity on health-related fitness and quality of life for
      patients with head and neck cancer: a systematic review.
AB  - BACKGROUND: Patients with head and neck cancer often face a plethora of cancer
      and treatment-related side effects, negatively impacting their lean body mass,
      physical functioning, quality of life and fatigue management. Physical activity
      is a potential mediator of many of these side effects. This is the first
      systematic review reporting on head and neck cancer and physical activity
      literature. METHODS: A literature search was conducted up to January 2015. Two
      reviewers independently identified articles using the outlined inclusion
      criteria, assessing the study methodology, risk of bias and extracting the
      necessary data from studies evaluating the impact of full-body physical activity
      on patients with head and neck cancer. The Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses Statement was used to guide this review.
      RESULTS: We identified 16 articles published from 2003 to 2014, the majority of
      which were published within the past 5 years. Physical activity interventions
      were feasible, safe and beneficial in mediating cancer and treatment-related side
      effects. Specifically, patients experienced improvements in lean body mass,
      muscular strength, physical functioning, quality of life and fatigue management.
      Owing to significant study heterogeneity, data were not pooled. Reflecting the
      early state of the literature, included studies were found to vary greatly in
      design, quality and reporting characteristics. CONCLUSIONS: There is early
      evidence that supports the benefit of physical activity interventions for
      patients with head and neck cancer, both during and following treatment. Future
      research is necessary to determine the benefits of different physical activity
      interventions, and their impact on patients with different head and neck cancers.

PMID- 25966912
TI  - Germline-derived DNA methylation and early embryo epigenetic reprogramming: The
      selected survival of imprints.
AB  - DNA methylation is an essential epigenetic mechanism involved in many essential
      cellular processes. During development epigenetic reprograming takes place during
      gametogenesis and then again in the pre-implantation embryo. These two
      reprograming windows ensure genome-wide removal of methylation in the primordial
      germ cells so that sex-specific signatures can be acquired in the sperm and
      oocyte. Following fertilization the majority of this epigenetic information is
      erased to give the developing embryo an epigenetic profile coherent with
      pluripotency. It is estimated that ~65% of the genome is differentially
      methylated between the gametes, however following embryonic reprogramming only
      parent-of-origin methylation at known imprinted loci remains. This suggests that
      trans-acting factors such as Zfp57 can discriminate imprinted differentially
      methylated regions (DMRs) from the thousands of CpG rich regions that are
      differentially marked in the gametes. Recently transient imprinted DMRs have been
      identified suggesting that these loci are also protected from pre-implantation
      reprograming but succumb to de novo remethylation at the implantation stage. This
      highlights that "ubiquitous" imprinted loci are also resilient to gaining
      methylation by protecting their unmethylated alleles. In this review I examine
      the processes involved in epigenetic reprograming and the mechanisms that ensure
      allelic methylation at imprinted loci is retained throughout the life of the
      organism, discussing the critical differences between mouse and humans. This
      article is part of a Directed Issue entitled: Epigenetics Dynamics in development
      and disease. 

PMID- 25966913
TI  - Experimental and mechanistic analysis of the palladium-catalyzed oxidative C8
      selective C-H homocoupling of quinoline N-oxides.
AB  - A novel site-selective palladium-catalyzed oxidative C8-H homocoupling reaction
      of quinoline N-oxides has been developed. The reaction affords substituted 8,8'
      biquinolyl N,N'-dioxides that can be readily converted to a variety of
      functionalized 8,8'-biquinolyls. Mechanistic studies point to the crucial role of
      the oxidant and a non-innocent behavior of acetic acid as a solvent. 

PMID- 25966914
TI  - New imaging assisted methods for liver fibrosis quantification: Is it really
      favorable to classical transient elastography?

PMID- 25966915
TI  - Pertussis Resurgence Associated with Pertactin-Deficient and Genetically
      Divergent Bordetella Pertussis Isolates in Israel.
AB  - The Bordetella pertussis polymerase chain reaction positivity rate changed after
      additional diphtheria-tetanus-acellular pertussis boosters in 2005 and 2008,
      9.8%, 13.4%, 22% and 15.2% in 2010, 2011, 2012 and 2013, P < 0.001, respectively.
      New pulsed-field gel electrophoresis profiles were detected between 2009 and
      2012. The proportion of pertactin-deficient isolates increased over time, 6.6%
      versus 7.1% versus 33.3% during 2005-2006, 2011-2012 and 2013-2014, P < 0.03,
      respectively. 

PMID- 25966916
TI  - First Experience of Concomitant Vaccination Against Dengue and MMR in Toddlers.
AB  - BACKGROUND: Dengue is a major public health concern in pediatric populations in
      endemic regions. A recombinant, live, attenuated, tetravalent dengue vaccine (CYD
      TDV) is under development for the control of dengue with a 3-dose (0-6-12 month)
      vaccination schedule. METHODS: In this controlled phase II trial conducted in the
      Philippines, 210 toddlers aged 12-15 months were randomized to 4 groups: 3 groups
      received the CYD-TDV vaccination schedule and a measles, mumps and rubella (MMR)
      vaccine given either concomitantly with the first CYD-TDV dose or 1 month
      earlier; 1 group received 3 active control vaccines. Safety and reactogenicity
      were assessed after each dose. Immunogenicity was assessed 30 days after
      vaccinations using the plaque reduction neutralization test against dengue and
      enzyme-linked immunosorbent assay methods against MMR antigens. RESULTS:
      Injection site and systemic reactions occurred at similar rates across CYD-TDV
      groups, except for fever, which was more frequent after CYD-TDV and MMR
      coadministration (28.8%) compared with other groups (12-20%). Reactogenicity did
      not increase with subsequent CYD-TDV injections. There were no safety issues with
      the study vaccine. CYD-TDV achieved a balanced antibody response to all 4 dengue
      serotypes across the study groups, with geometric mean titers in the range of 105
      124, 147-213, 311-387 and 127-160 for serotypes 1, 2, 3 and 4, respectively. CYD
      TDV coadministration did not affect MMR immunogenicity (>=95% seroprotection
      against MMR) and vice versa. CONCLUSIONS: The CYD-TDV has an acceptable safety
      and immunogenicity profile in toddlers and when coadministered with MMR.

PMID- 25966917
TI  - A Girl with Disseminated Thoracic Echinococcosis.
AB  - We present an unusual case of extensively disseminated pulmonary and thoracic
      echinococcosis in a 10-year-old girl. Thoracic echinococcosis should be
      considered in any child from an endemic country with cystic lesions on chest
      imaging. Confirmation of the diagnosis can be difficult and is important before
      surgery to reduce the risk of further dissemination and anaphylaxis. 

PMID- 25966918
TI  - "A Defective and Imperfect" Method: H. Christian Gram and the History of the Gram
      Stain.

PMID- 25966919
TI  - What physicians need to know about renal function in outpatients with heart
      failure.
AB  - The majority of outpatients with heart failure (HF) have chronic kidney disease
      (CKD) as an important comorbidity. Both glomerular filtration rate and abnormal
      urinary albumin excretion are major predictors of outcome in HF patients. Despite
      this, patients with renal dysfunction have been systematically excluded from the
      large randomized HF trials. There is lack of evidence for optimal treatment in
      these cardiorenal patients and treatment nihilism may account in part for their
      bad prognosis. Identifying and monitoring the progression of renal disease and
      making an effort to preserve renal function should be an important task in the
      management of all patients with HF. In this review, the current understanding of
      the pathophysiology of renal dysfunction in outpatients with HF will be
      summarized. Furthermore, important principles of the identification and
      management of cardiorenal patients will be described in order to make the
      physician more capable of managing outpatients with HF and renal dysfunction.

PMID- 25966920
TI  - Model of unidirectional block formation leading to reentrant ventricular
      tachycardia in the infarct border zone of postinfarction canine hearts.
AB  - BACKGROUND: When the infarct border zone is stimulated prematurely, a
      unidirectional block line (UBL) can form and lead to double-loop (figure-of
      eight) reentrant ventricular tachycardia (VT) with a central isthmus. The isthmus
      is composed of an entrance, center, and exit. It was hypothesized that for
      certain stimulus site locations and coupling intervals, the UBL would coincide
      with the isthmus entrance boundary, where infarct border zone thickness changes
      from thin-to-thick in the travel direction of the premature stimulus wavefront.
      METHOD: A quantitative model was developed to describe how thin-to-thick changes
      in the border zone result in critically convex wavefront curvature leading to
      conduction block, which is dependent upon coupling interval. The model was tested
      in 12 retrospectively analyzed postinfarction canine experiments. Electrical
      activation was mapped for premature stimulation and for the first reentrant VT
      cycle. The relationship of functional conduction block forming during premature
      stimulation to functional block during reentrant VT was quantified. RESULTS: For
      an appropriately placed stimulus, in accord with model predictions: (1) The UBL
      and reentrant VT isthmus lateral boundaries overlapped (error: 4.8+/-5.7mm). (2)
      The UBL leading edge coincided with the distal isthmus where the center-entrance
      boundary would be expected to occur. (3) The mean coupling interval was 164.6+/
      11.0ms during premature stimulation and 190.7+/-20.4ms during the first reentrant
      VT cycle, in accord with model calculations, which resulted in critically convex
      wavefront curvature with functional conduction block, respectively, at the
      location of the isthmus entrance boundary and at the lateral isthmus edges.
      DISCUSSION: Reentrant VT onset following premature stimulation can be explained
      by the presence of critically convex wavefront curvature and unidirectional block
      at the isthmus entrance boundary when the premature stimulation interval is
      sufficiently short. The double-loop reentrant circuit pattern is a consequence of
      wavefront bifurcation around this UBL followed by coalescence, and then impulse
      propagation through the isthmus. The wavefront is blocked from propagating
      laterally away from the isthmus by sharp increases in border zone thickness,
      which results in critically convex wavefront curvature at VT cycle lengths.

PMID- 25966921
TI  - Medical data sheet in safe havens - A tri-layer cryptic solution.
AB  - Secured sharing of the diagnostic reports and scan images of patients among
      doctors with complementary expertise for collaborative treatment will help to
      provide maximum care through faster and decisive decisions. In this context, a
      tri-layer cryptic solution has been proposed and implemented on Digital Imaging
      and Communications in Medicine (DICOM) images to establish a secured
      communication for effective referrals among peers without compromising the
      privacy of patients. In this approach, a blend of three cryptic schemes, namely
      Latin square image cipher (LSIC), discrete Gould transform (DGT) and Rubik's
      encryption, has been adopted. Among them, LSIC provides better substitution,
      confusion and shuffling of the image blocks; DGT incorporates tamper proofing
      with authentication; and Rubik renders a permutation of DICOM image pixels. The
      developed algorithm has been successfully implemented and tested in both the
      software (MATLAB 7) and hardware Universal Software Radio Peripheral (USRP)
      environments. Specifically, the encrypted data were tested by transmitting them
      through an additive white Gaussian noise (AWGN) channel model. Furthermore, the
      sternness of the implemented algorithm was validated by employing standard
      metrics such as the unified average changing intensity (UACI), number of pixels
      change rate (NPCR), correlation values and histograms. The estimated metrics have
      also been compared with the existing methods and dominate in terms of large key
      space to defy brute force attack, cropping attack, strong key sensitivity and
      uniform pixel value distribution on encryption. 

PMID- 25966922
TI  - A fully automatic 2D segmentation method for uterine fibroid in MRgFUS treatment
      evaluation.
AB  - PURPOSE: Magnetic Resonance guided Focused UltraSound (MRgFUS) represents a non
      invasive surgical approach that uses thermal ablation to treat uterine fibroids.
      After the MRgFUS treatment, an operator must manually segment the treated fibroid
      areas to evaluate the NonPerfused Volume (NPV). This manual approach is operator
      dependent, introducing issues of result reproducibility, which could lead to
      errors in the subsequent follow-up phase. Moreover, manual segmentation is time
      consuming, and can have a negative impact on the optimization of both machine
      time and operator-time. METHOD: To address these issues, in this paper a novel
      fully automatic method based on the unsupervised Fuzzy C-Means clustering and
      iterative optimal threshold selection algorithms for uterus and fibroid
      segmentation is proposed. The developed method could be used to enhance the
      current manual methodology performed by healthcare operators for post-operative
      NPV evaluation in uterine fibroid MRgFUS treatments. RESULTS: The proposed method
      was tested on 15 MR datasets of 15 different patients with uterine fibroids and
      evaluated using area-based and distance-based metrics. A comparison of extracted
      volume was also performed. Average values for fibroid (ROT) segmentation are
      SDI=88.67%, JI=80.70%, SE=89.79%, SP=88.73%, MAD=2.200 [pixels], MAXD=6.233
      [pixels] and HD=2.988 [pixels]. Moreover, to make a quantitative evaluation of
      this method, our experimental results were compared with similar literature
      approaches. CONCLUSIONS: The proposed method provides a practical approach for
      the automatic evaluation of the boundary and volume of ablated fibroid regions,
      without any external user input. The achieved segmentation results show the
      validity and the effectiveness of the proposed solution.

PMID- 25966923
TI  - Perfluoroalkyl substances in a firefighting training ground (FTG), distribution
      and potential future release.
AB  - The present study investigates the occurrence and fate of 15 perfluoroalkyl
      substances (PFASs) and one fluorotelomer sulfonate from a firefighting training
      ground (FTG) that was contaminated by intensive use of aqueous film forming foams
      (AFFF). The contamination levels and their spatial and vertical distribution are
      assessed in the structure. At the surface of the pad, perfluorooctane sulphonate
      (PFOS) is the dominant PFASs measured, with concentration varying from 10 to 200
      MUg g(-1). PFASs were also detected in a concrete core at up to 12 cm depth,
      suggesting the vertical movement and higher transport potential of shorter chain
      compounds. The estimated mass load of linear PFOS in this specific pad was >300 g
      with a total of 1.7 kg for the sum of all PFASs analyzed. The kinetics of
      desorption of PFOS, PFOA and 6:2FTS from the concrete into an overlaying static
      water volume has been measured under field conditions at two constant
      temperatures. Fitting the desorption data and estimated rainfall/runoff to a
      kinetic model suggests that this and similar firefighting training pads will
      likely remain a source of PFASs for many decades (t0.5=25 years for PFOS).

PMID- 25966924
TI  - Integrating electrochemical oxidation into forward osmosis process for removal of
      trace antibiotics in wastewater.
AB  - During the rejection of trace pharmaceutical contaminants from wastewater by
      forward osmosis (FO), disposal of the FO concentrate was still an unsolved issue.
      In this study, by integrating the advantages of forward osmosis and
      electrochemical oxidation, a forward osmosis process with the function of
      electrochemical oxidation (FOwEO) was established for the first time to achieve
      the aim of rejection of trace antibiotics from wastewater and treatment of the
      concentrate at the same time. Results demonstrated that FOwEO (current density
      J=1 mA cm(-2)) exhibited excellent rejections of antibiotics (>98%) regardless of
      different operation conditions, and above all, antibiotics in the concentrate
      were well degraded (>99%) at the end of experiment (after 3h). A synergetic
      effect between forward osmosis and electrochemical oxidation was observed in
      FOwEO, which lies in that antibiotic rejections by FO were enhanced due to the
      degradation of antibiotics in the concentrate, while the electrochemical
      oxidation capacity was improved in the FOwEO channel, of which good mass transfer
      and the assist of indirect oxidation owing to the reverse NaCl from draw solution
      were supposed to be the mechanism. This study demonstrated that the FOwEO has the
      capability to thoroughly remove trace antibiotics from wastewater.

PMID- 25966925
TI  - Exocytic and endocytic membrane trafficking in axon development.
AB  - In the complex neuronal circuits in the nervous systems, billions of neurons are
      precisely interconnected by long, thin processes called the axons. The growth
      cone, a highly motile structure at the tip of an extending axon, navigates by
      responding to a variety of extracellular molecular cues toward their distant
      target cells and make synaptic connections. Emerging evidence indicates that
      exocytic and endocytic membrane trafficking systems play multiple important roles
      in the regulation of such axonal morphogenetic processes. Exocytosis and
      endocytosis organize the subcellular distribution of membrane-associated
      molecules, such as receptors, cell adhesion molecules, and cytoskeletal
      regulators, to control intracellular signaling and driving machineries.
      Furthermore, the exocytosis of trophic factors and extracellular proteinases act
      on surrounding microenvironments to affect growth cone motility. In this Review
      Article, we summarize our current understanding of the regulation and function of
      exocytic and endocytic membrane trafficking in axon morphogenesis during
      development, and discuss potential mechanisms of how the membrane trafficking
      systems exert such morphological changes. 

PMID- 25966926
TI  - Aberrant expression of regulatory cytokine IL-35 in patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: This study characterizes an IL-35-mediated regulatory role in patients
      with systemic lupus erythematosus (SLE). METHODS: Plasma of SLE patients and
      healthy controls (HCs) was analyzed for the concentrations of IL-35 and soluble
      gp130 by using ELISA. mRNA expression of IL-35 subunit (p35 and EBI3) and its
      receptor (gp130 and IL-12Rbeta2) in peripheral blood mononuclear cells (PBMCs)
      was assessed by RT-qPCR. Flow cytometry was performed to evaluate the number of
      CD4(+)CD25(high)CD127(-)Treg cells and the expression of IL-35 receptor on the
      CD4+ helper (Th) cells and CD19+ B cells. Plasma collected from SLE patients and
      HCs was assayed for cytokine and chemokine expression by Luminex multiplex assay.
      RESULTS: Plasma IL-35 and soluble gp130 levels positively correlated with each
      other and were significantly higher in patients with severe SLE compared with
      HCs. Significantly higher levels of inflammatory cytokines/chemokines CCL2,
      CXCL8, IL-6, interferon (IFN)-gamma, IL-10 and IL-17A were observed in plasma of
      SLE patients than HCs. mRNA levels of IL-35 and its receptor were significantly
      positively correlated in PBMCs from SLE patients and their levels were higher in
      SLE than HCs. The increase significantly correlated with changes in SLE Disease
      Activity Index (SLEDAI) (all p < 0.05). In addition, the number of Treg cells in
      severe and moderate SLE patients were both significantly lower than HCs, where
      the ratio of CD4(+)CD25(-)effector T cell %/CD4(+)CD25(high)CD127(-)Treg % was
      found to be significantly higher in severe SLE patients. Furthermore, the
      expression of gp130 on CD4+ Th cells and percentage of Tregs were positively
      correlated with each other, and both were negatively correlated with SLEDAI.
      CONCLUSION: Our findings indicate that high level of plasma IL-35 in active SLE
      patients expressed with low level of IL-35 receptor (gp130) on CD4+ Th cells.
      These data raise the possibility that the level of IL-35 expression in SLE
      patients is not sufficient to induce the production of CD4(+)CD25(high)CD127(
      )Tregs, and subsequently suppress the release of inflammatory cytokines and
      chemokines upon inflammation.

PMID- 25966927
TI  - Adherence to online monitoring of patient-reported outcomes by patients with
      chronic inflammatory diseases: a feasibility study.
AB  - OBJECTIVES: The objective of this report is to investigate the feasibility of
      collecting patient-reported outcomes (PROs) via e-questionnaires delivered to
      patients with chronic inflammatory diseases (CIDs). METHODS: Consecutive
      outpatients with a confirmed diagnosis of systemic lupus erythematosus, primary
      Sjogren's syndrome or inflammatory bowel disease were followed at two medical
      departments. Patients received monthly e-mails containing the SF36, Hospital
      Anxiety and Depression scale and an analogue symptom scale over a six-month
      period. Participation rate, socio-demographic characteristics and patients'
      satisfaction were analysed. RESULTS: A total of 128 patients were included (79%
      female; mean age: 42 +/- 12 years). Eighty-two per cent of questionnaires were
      returned. The monthly participation rate ranged from 89% to 77%, with a six-month
      attrition rate of 13%. The mean completion rate of questionnaires was 98%.
      Factors significantly associated with increased answer rate were: married/couple
      status, greater number of children at home and previous participation in online
      surveys. The main reasons for non-response were: 'too busy to participate' (35%)
      and 'away from home Internet access' (31%). Overall, 68% of the participants
      found the study convenient and 96% agreed to continue at a monthly or bimonthly
      frequency. CONCLUSION: Online home self-assessment of PROs was feasible in the
      setting of CIDs. Patients were satisfied and willing to continue the survey. The
      Internet allows immediate and sophisticated presentation of PROs to clinicians.
      Future studies are warranted to determine how PRO monitoring may contribute to
      routine care in CIDs and other diseases.

PMID- 25966928
TI  - Systemic lupus erythematosus occurring in a patient with Niemann-Pick type B
      disease.
AB  - Niemann-Pick disease is an inherited lipid storage disorder caused by the
      deficiency of acid sphingomyelinase, which results in accumulation of
      sphingomyelin within cells of several organs and consequent tissue damage. The
      broad clinical spectrum of this disorder may overlap with that of systemic lupus
      erythematosus, hindering differential diagnosis. Herein, we report the case of a
      patient affected by Niemann-Pick type B disease intertwined with clinical and
      serological features of systemic lupus erythematosus. Two novel mutations in the
      SMPD1 gene were found in compound heterozygosity: p.A36V and IVS2 + 8 T > G. 

PMID- 25966930
TI  - Multilevel memristor effect in metal-semiconductor core-shell nanoparticles
      tested by scanning tunneling spectroscopy.
AB  - We have grown gold (Au) and copper-zinc-tin-sulfide (CZTS) nanocrystals and Au
      CZTS core-shell nanostructures, with gold in the core and the semiconductor in
      the shell layer, through a high-temperature colloidal synthetic approach.
      Following usual characterization, we formed ultrathin layers of these in order to
      characterize the nanostructures in an ultrahigh-vacuum scanning tunneling
      microscope. Scanning tunneling spectroscopy of individual nanostructures showed
      the memristor effect or resistive switching from a low- to a high-conducting
      state upon application of a suitable voltage pulse. The Au-CZTS core-shell
      nanostructures also show a multilevel memristor effect with the nanostructures
      undergoing two transitions in conductance at two magnitudes of voltage pulse. We
      have studied the reproducibility, reversibility, and retentivity of the
      multilevel memristors. From the normalized density of states (NDOS), we infer
      that the memristor effect is correlated to a decrease in the transport gap of the
      nanostructures. We also infer that the memristor effect occurs in the
      nanostructures due to an increase in the density of available states upon
      application of a voltage pulse. 

PMID- 25966929
TI  - Improved disease markers suggest dual response in a patient with metastatic
      castration resistant prostate cancer and chronic lymphocytic leukemia following
      active cellular immunotherapy.
AB  - Prostate cancer and chronic lymphocytic leukemia (CLL) are relatively common
      malignancies associated with advanced age. Although immunotherapy-based
      strategies are used to treat both, currently, there is no overlap in specific
      therapies. Sipuleucel-T is an active cellular immunotherapy that improves overall
      survival for patients with metastatic castration resistant prostate cancer
      (mCRPC) but is not typically associated with a decline in prostate-specific
      antigen (PSA) following administration. We report the case of a 78-year-old man
      with mCRPC and Rai stage 0 CLL who sustained a 12-month decline in both PSA and
      white blood cell (WBC) count following treatment with APC8015-2 (an
      investigational form of sipuleucel-T), as part of the phase II ProACT clinical
      trial. Two years later, the patient received commercial sipuleucel-T and again
      was noted to have a decline in PSA. Exploratory analysis did not clearly identify
      any peripheral immune markers associated with response. This case report suggests
      that treatment with sipuleucel-T can rarely lead to PSA decline, may have dual
      activity against both prostate cancer and CLL, and that these findings warrant
      further investigation. 

PMID- 25966931
TI  - Cerebral white matter volume changes in patients with obsessive-compulsive
      disorder: Voxel-based morphometry.
AB  - AIMS: We carried out a voxel-based morphometry (VBM) study to evaluate cerebral
      white matter (WM) volume alteration in obsessive-compulsive disorder (OCD) and
      its correlation with the scores of the Yale-Brown Obsessive-Compulsive Scale (Y
      BOCS). METHODS: Fourteen patients with OCD, who were diagnosed using the DSM-IV
      TR, and 14 age-matched healthy controls participated. The high-resolution
      magnetic resonance imaging data were analyzed by voxel-based morphometry and
      Statistical Parametric Mapping 8. RESULTS: There was no significant difference in
      the total intracranial volumes between OCD patients and healthy controls.
      However, patients with OCD showed significantly increased WM volumes in the right
      dorsolateral prefrontal cortex, middle frontal gyrus, precuneus, and inferior
      parietal lobule compared with healthy controls. In addition, the OCD patients
      showed a positive correlation between the WM volumes of the dorsolateral
      prefrontal cortex and Y-BOCS scores (r = 0.334, P = 0.03 and Pearson's
      correlation coefficient = 0.58) rating for the severity of OCD symptoms.
      CONCLUSIONS: WM volume variations of the specific brain regions in patients with
      OCD will be helpful to understand the neural connectivity associated with a
      symptom of OCD. Furthermore, the findings would be valuable to aid the diagnostic
      accuracy of OCD in connection with morphometric magnetic resonance imaging
      analysis.

PMID- 25966932
TI  - Lifestyle and Weight Management Counseling in Uterine Cancer Survivors: A Study
      of the Uterine Cancer Action Network.
AB  - OBJECTIVE: The purpose of this study was to examine the experiences, attitudes,
      and preferences of uterine cancer survivors with regard to weight and lifestyle
      counseling. MATERIALS AND METHODS: Members of the US Uterine Cancer Action
      Network of the Foundation for Women's Cancer were invited to complete a 45-item,
      Web-based survey. Standard descriptive statistical methods and chi tests were
      used to analyze responses. RESULTS: One hundred eighty (28.3%) uterine cancer
      survivors completed the survey. Median age was 58 years, 85% were white, and
      median survivorship period was 4.4 years. Most had stage I-II disease (69%) and
      were overweight or obese (65%). Eighty-nine percent of respondents received care
      by a gynecologic oncologist. Increased respondent body mass index was associated
      with decreased exercise frequency (P = 0.016). Only 50% of respondents underwent
      any weight/lifestyle counseling, with those living in the West and Southwest
      reporting the highest rates (70.8% and 69.2%, P = 0.011). Most who received
      counseling felt that discussions were motivating, performed in a sensitive
      manner, and did not undermine the patient-physician relationship. Specific
      recommendations were rarely offered; there were no reported referrals to weight
      loss programs or bariatric specialists, and few (6%) reported referrals to
      nutritionists. Respondents (85%) preferred their gynecologic oncologist address
      weight using direct, face-to-face counseling with specific recommendations
      regarding interventions and referral to specialists. Finally, self-reported
      overweight respondents experienced greater success with weight loss compared to
      those reporting obesity or morbid obesity (30.8% vs 15.8% vs 12.5%, P = 0.011).
      CONCLUSIONS: Uterine cancer survivors reported high obesity, low activity rates,
      and a desire for substantive weight loss counseling from their gynecologic
      oncologists. Respondents suggested that current counseling practices are
      inadequate and incongruent with their needs. Further research to define optimal
      timing, interventional strategies, and specific recommendations for successful
      lifestyle changes in this population is warranted.

PMID- 25966933
TI  - Clinical Application of Diffusion-Weighted Magnetic Resonance Imaging in Uterine
      Cervical Cancer.
AB  - OBJECTIVE: This study aimed to investigate the application value of apparent
      diffusion coefficient (ADC) values in evaluating histological type as well as
      pathologic grade of uterine cervical cancer; and to investigate whether ADC
      values could reflect tumor cellular density. METHODS: Ninety-eight patients with
      histopathologically proven uterine cervical cancer were included in this study.
      Mean ADC value and minimum ADC value of the tumor were measured. Tumor cellular
      density was counted using colored multifunction imaging analyzing system.
      RESULTS: Both mean ADC value and minimum ADC value of squamous cell carcinoma
      were significantly lower than that of adenocarcinoma (P = 0.001; P = 0.000).
      Using mean ADC criteria (<=0.965 * 10-3 mm/s2) and minimum ADC criteria (<=0.844
      * 10-3 mm/s2), the sensitivity and specificity for differentiating squamous cell
      carcinoma from adenocarcinoma were 83.5% and 76.9%, and 77.6% and 92.3%,
      respectively. Receiver operating characteristic analysis revealed that there was
      no statistically significant difference in the Az values between them (P =
      0.990). Tumor cellular density, mean ADC value, and minimum ADC value of
      different pathological grade varied significantly (P = 0.000, P = 0.000, P =
      0.000). There was a significant positive linear correlation between tumor
      cellular density and pathological grade of tumor (P = 0.000). Both mean ADC value
      and minimum ADC value correlated negatively with cellular density (P = 0.000, P =
      0.000) and the pathological grade of tumor (P = 0.000, P = 0.000). Comparisons of
      correlation coefficients showed no significant differences (P = 0.656, P =
      0.631). CONCLUSIONS: Diffusion-weighted magnetic resonance imaging has a
      potential ability to indicate the histologic type of uterine cervical cancer.
      Apparent diffusion coefficient measurements of uterine cervical cancer can
      represent tumor cellular density, thus providing a new method for evaluating the
      pathological grade of tumor.

PMID- 25966934
TI  - Treatment of permanent chemotherapy-induced alopecia with low dose oral
      minoxidil.
AB  - Chemotherapy-induced alopecia is a well-established cause of major distress to
      patients. Permanent chemotherapy-induced alopecia (PCIA) is the absence of or
      incomplete hair regrowth lasting longer than 6 months after the cessation of
      chemotherapy and it does not respond to standard treatments of scalp cooling or
      topical minoxidil. The increasing numbers of reports of PCIA highlight the need
      for research into an effective treatment. We report a case of a 39 year-old woman
      with cosmetically significant regrowth after continuous therapy with oral
      minoxidil.

PMID- 25966935
TI  - Kinetics of the heterogeneous photo oxidation of the pesticide bupirimate by OH
      radicals and ozone under atmospheric conditions.
AB  - This article is concerned with the study of the photochemical degradation of
      bupirimate adsorbed on a quartz surface by atmospheric oxidants, namely ozone and
      OH radicals. OH oxidation experiments were conducted relative to two reference
      compounds, terbuthylazine and (4-chlorophenyl)(3,4-dimethoxyphenyl) methanone.
      Meanwhile, ozone oxidation experiments were performed in the absolute mode and
      were interpreted by both, the Surface Layer Reaction and the Gas Surface Reaction
      models of heterogeneous reactions. The obtained results show that the rate
      constants for the reactions between bupirimate and OH radicals and ozone are
      (cm(3)molecule(-1)s(-1)): (1.06 +/- 0.87) * 10(-12) and (5.4 +/- 0.3) * 10(-20),
      respectively. As a consequence, for the experimental conditions used in this
      study, the lifetime of bupirimate at quartz like surface/atmosphere interfaces is
      several months against ozone and a tenth of days against OH-radical.

PMID- 25966936
TI  - Short term uptake and transport process for metformin in roots of Phragmites
      australis and Typha latifolia.
AB  - Metformin (MET) as an emerging contaminant has been detected in surface water and
      wastewater in numerous countries, due to insufficient retention in classical
      waste water treatment plants. In order to characterize the uptake of the compound
      during phytotreatment of waste water, a short term Pitman chamber experiment was
      carried out to assess the characteristics of MET uptake and transport by roots.
      Three different concentrations (0.5, 1.0 and 2.0 mmol L(-)(1)) were applied to
      cattail (Typha latifolia) and reed (Phragmites australis) roots which were used
      to investigate the uptake mechanism because they are frequently utilized in
      phytoremediation. In addition, quinidine was used as an inhibitor to assess the
      role of organic cation transporters (OCTs) in the uptake of MET by T. latifolia.
      The transport process of MET is different from carbamazepine (CBZ) and caffeine
      (CFN). In both T. latifolia and P. australis, the uptake processes were
      independent of initial concentrations. Quinidine, a known inhibitor of organic
      cation transporters, can significantly affect MET uptake by T. latifolia roots
      with inhibition ratios of 70-74%. Uptake into the root could be characterized by
      a linear model with R(2) values in the range of 0.881-0.999. Overall, the present
      study provides evidence that MET is taken up by plant roots and has the potential
      for subsequent translocation. OCTs could be one of the important pathways for MET
      uptake into the plant.

PMID- 25966937
TI  - Sunlight-induced degradation of fluoroquinolones in wastewater effluent:
      Photoproducts identification and toxicity.
AB  - The photodegradation of Ciprofloxacin (CIP), Enrofloxacin (ENR), Danofloxacin
      (DAN), Marbofloxacin (MAR) and Levofloxacin (LEV), five widely used
      fluoroquinolones (FQs), was studied in urban WWTP secondary effluent, under solar
      light. The degradation profiles and the kinetic constants were determined at the
      micrograms per litre levels (20-50 MUg L(-1)). The photo-generated products were
      identified by high-pressure liquid chromatography coupled to electrospray
      ionization tandem mass spectrometry (HPLC-ESI-MS/MS). The toxicity of the
      photoproducts was assessed by Vibrio fischeri light emission inhibition assay
      performed on irradiated and not-irradiated FQs solutions, at environmentally
      significant concentrations. Attention was focused on the evaluation of the
      photoproducts contribution to the overall biotoxic effect of these emerging
      pollutants. Data from chronic exposure experiments (24-48 h) were primarily
      considered. Results confirmed the major usefulness of chronic toxicity data with
      respect to the acute assay ones and proved the not negligible biotoxicity of the
      FQs photodegradation products.

PMID- 25966938
TI  - Reconstructing the history of mining and remediation in the Coeur d'Alene, Idaho
      Mining District using lake sediments.
AB  - Mining that began in the late 1800s intensified during World War II contaminating
      Lake Coeur d'Alene sediments with potentially toxic elements. We used 80y of the
      sediment record to reconstruct metal(loid) loadings to the lake and
      quantitatively evaluate the effectiveness of tailings management. Sediment core
      analysis for pollen, chronological markers, and metal(loid)s permitted
      stratigraphic reconstruction showing that contaminant loading decreased after
      tailings pond construction, but that most metal(loid) concentrations exceed
      recommended limits. Arsenic concentrations (250-450 mg kg(-)(1)) at the sediment
      water interface are potentially toxic; however, low P concentrations in recent
      sediments (1.0-1.4 mg kg(-)(1)) inhibit eutrophication and the concomitant
      release of soluble As. Zinc (3 g kg(-)(1)), Cd (10 mg kg(-)(1)), Ag (10 mg kg(
      )(1)), and Cu (90 mg kg(-)(1)) concentrations are now lower than in sediments
      deposited during active mining, but remain an environmental concern. Sedimentary
      Cr and Pb concentrations have not changed in the last 50y, because tailings
      continue to enter the lake. Although modern Cr concentrations (40 mg kg(-)(1))
      are unlikely to cause toxicity, current Pb concentrations (4 g kg(-)(1)) exceed
      acceptable limits, creating challenges for remediation. Strategies to manage
      other mining-contaminated watersheds should include consideration of elemental
      differences when evaluating remediation effectiveness.

PMID- 25966939
TI  - Influence of population density on the concentration and speciation of metals in
      the soil and street dust from urban areas.
AB  - Street dust and soil from high, medium and low populated cities and natural area
      were analysed for selected physical-chemical properties, total and chemical
      speciation of Zn, Pb, Cu, Cr, Cd, Co, Ni to understand the influence of human
      activities on metal accumulation and mobility in the environment. The pH,
      salinity, carbonates and organic carbon contents were similar between soil and
      dust from the same city. Population density increases dust/soil salinity but has
      no influence on metals concentrations in soils. Increases in metal concentrations
      with population density were observed in dusts. Cu, Zn, Pb, Cr can be mobilized
      more easily from dust compared to the soil. In addition, population density
      increase the percentage of Pb and Zn associated to reducible and carbonate phase
      in the dust. The behaviour of metals except Cd in soil is mainly affected by
      physico-chemical properties, while total metal influenced the speciation except
      Cr and Ni in dusts. 

PMID- 25966940
TI  - Transmission of the eyeworm Thelazia callipaeda: between fantasy and reality.
AB  - BACKGROUND: Thelazia callipaeda is transmitted by Phortica variegata, a
      drosophilid that feeds on lachrymal secretions of mammals. Scientific information
      on human thelaziosis is still relatively limited, mainly for physicians and
      ophthalmologists. Indeed, the literature is full of misleading information on the
      transmission of T. callipaeda to humans. FINDINGS: A recent paper reported a case
      of human intraocular infestation in a patient from Karnataka. The information
      presented in that article as well as in other articles in the international
      literature is outdated and incorrect in several instances, mostly regarding to
      the localization of T. callipaeda in the host, its biology and routes of
      transmission. CONCLUSIONS: Physicians and ophthalmologists should be aware that
      T. callipaeda is larviparous and transmitted exclusively by secretophagous flies.
      These flies buzz around the eyes of animals and humans at the daytime, landing on
      the eyes and releasing the infective larvae on the host conjunctiva. That is the
      only possible way of transmission of T. callipaeda.

PMID- 25966941
TI  - Method for rapid MRI quantification of global cerebral metabolic rate of oxygen.
AB  - A recently reported quantitative magnetic resonance imaging (MRI) method denoted
      OxFlow has been shown to be able to quantify whole-brain cerebral metabolic rate
      of oxygen (CMRO2) by simultaneously measuring oxygen saturation (SvO2) in the
      superior sagittal sinus and cerebral blood flow (CBF) in the arteries feeding the
      brain in 30 seconds, which is adequate for measurement at baseline but not
      necessarily in response to neuronal activation. Here, we present an accelerated
      version of the method (referred to as F-OxFlow) that quantifies CMRO2 in 8
      seconds scan time under full retention of the parent method's capabilities and
      compared it with its predecessor at baseline in 10 healthy subjects. Results
      indicate excellent agreement between both sequences, with mean bias of 2.2%
      (P=0.18, two-tailed t-test), 3.4% (P=0.08, two-tailed t-test), and 2.0% (P=0.56,
      two-tailed t-test) for SvO2, CBF, and CMRO2, respectively. F-OxFlow's potential
      to monitor dynamic changes in SvO2, CBF, and CMRO2 is illustrated in a paradigm
      of volitional apnea applied to five of the study subjects. The sequence captured
      an average increase in SvO2, CBF, and CMRO2 of 10.1+/-2.5%, 43.2+/-9.2%, and
      7.1+/-2.2%, respectively, in good agreement with literature values. The method
      may therefore be suited for monitoring alterations in CBF and SvO2 in response to
      neurovascular stimuli. 

PMID- 25966942
TI  - Altered contralateral sensorimotor system organization after experimental
      hemispherectomy: a structural and functional connectivity study.
AB  - Hemispherectomy is often followed by remarkable recovery of cognitive and motor
      functions. This reflects plastic capacities of the remaining hemisphere,
      involving large-scale structural and functional adaptations. Better understanding
      of these adaptations may (1) provide new insights in the neuronal configuration
      and rewiring that underlies sensorimotor outcome restoration, and (2) guide
      development of rehabilitation strategies to enhance recovery after hemispheric
      lesioning. We assessed brain structure and function in a hemispherectomy model.
      With MRI we mapped changes in white matter structural integrity and gray matter
      functional connectivity in eight hemispherectomized rats, compared with 12
      controls. Behavioral testing involved sensorimotor performance scoring. Diffusion
      tensor imaging and resting-state functional magnetic resonance imaging were
      acquired 7 and 49 days post surgery. Hemispherectomy caused significant
      sensorimotor deficits that largely recovered within 2 weeks. During the recovery
      period, fractional anisotropy was maintained and white matter volume and axial
      diffusivity increased in the contralateral cerebral peduncle, suggestive of
      preserved or improved white matter integrity despite overall reduced white matter
      volume. This was accompanied by functional adaptations in the contralateral
      sensorimotor network. The observed white matter modifications and reorganization
      of functional network regions may provide handles for rehabilitation strategies
      improving functional recovery following large lesions. 

PMID- 25966943
TI  - Protective role of Kv7 channels in oxygen and glucose deprivation-induced damage
      in rat caudate brain slices.
AB  - Ischemic stroke can cause striatal dopamine efflux that contributes to cell
      death. Since Kv7 potassium channels regulate dopamine release, we investigated
      the effects of their pharmacological modulation on dopamine efflux, measured by
      fast cyclic voltammetry (FCV), and neurotoxicity, in Wistar rat caudate brain
      slices undergoing oxygen and glucose deprivation (OGD). The Kv7 activators
      retigabine and ICA27243 delayed the onset, and decreased the peak level of
      dopamine efflux induced by OGD; and also decreased OGD-induced damage measured by
      2,3,5-triphenyltetrazolium chloride (TTC) staining. Retigabine also reduced OGD
      induced necrotic cell death evaluated by lactate dehydrogenase activity assay.
      The Kv7 blocker linopirdine increased OGD-evoked dopamine efflux and OGD-induced
      damage, and attenuated the effects of retigabine. Quantitative-PCR experiments
      showed that OGD caused an ~6-fold decrease in Kv7.2 transcript, while levels of
      mRNAs encoding for other Kv7 subunits were unaffected; western blot experiments
      showed a parallel reduction in Kv7.2 protein levels. Retigabine also decreased
      the peak level of dopamine efflux induced by L-glutamate, and attenuated the loss
      of TTC staining induced by the excitotoxin. These results suggest a role for
      Kv7.2 in modulating ischemia-evoked caudate damage. 

PMID- 25966944
TI  - Vascular permeability in cerebral cavernous malformations.
AB  - Patients with the familial form of cerebral cavernous malformations (CCMs) are
      haploinsufficient for the CCM1, CCM2, or CCM3 gene. Loss of corresponding CCM
      proteins increases RhoA kinase-mediated endothelial permeability in vitro, and in
      mouse brains in vivo. A prospective case-controlled observational study
      investigated whether the brains of human subjects with familial CCM show vascular
      hyperpermeability by dynamic contrast-enhanced quantitative perfusion magnetic
      resonance imaging, in comparison with CCM cases without familial disease, and
      whether lesional or brain vascular permeability correlates with CCM disease
      activity. Permeability in white matter far (WMF) from lesions was significantly
      greater in familial than in sporadic cases, but was similar in CCM lesions.
      Permeability in WMF increased with age in sporadic patients, but not in familial
      cases. Patients with more aggressive familial CCM disease had greater WMF
      permeability compared to those with milder disease phenotype, but similar lesion
      permeability. Subjects receiving statin medications for routine cardiovascular
      indications had a trend of lower WMF, but not lesion, permeability. This is the
      first demonstration of brain vascular hyperpermeability in humans with an
      autosomal dominant disease, as predicted mechanistically. Brain permeability,
      more than lesion permeability, may serve as a biomarker of CCM disease activity,
      and help calibrate potential drug therapy. 

PMID- 25966945
TI  - High daytime and nighttime ambulatory  pulse pressure predict poor cognitive 
      function and mild cognitive impairment  in hypertensive individuals.
AB  - High blood pressure accelerates normal aging stiffness process. Arterial
      stiffness (AS) has been previously associated with impaired cognitive function
      and dementia. Our aims are to study how cognitive function and status (mild
      cognitive impairment, MCI and normal cognitive aging, NCA) relate to AS in a
      community-based population of hypertensive participants assessed with office and
      24-hour ambulatory blood pressure measurements. Six hundred ninety-nine
      participants were studied, 71 had MCI and the rest had NCA. Office pulse pressure
      (PP), carotid-femoral pulse wave velocity, and 24-hour ambulatory PP monitoring
      were collected. Also, participants underwent a brain magnetic resonance to study
      cerebral small-vessel disease (cSVD) lesions. Multivariate analysis-related
      cognitive function and cognitive status to AS measurements after adjusting for
      demographic, vascular risk factors, and cSVD. Carotid-femoral pulse wave velocity
      and PP at different periods were inversely correlated with several cognitive
      domains, but only awake PP measurements were associated with attention after
      correcting for confounders (beta = -0.22, 95% confidence interval (CI) -0.41, 
      0.03). All ambulatory PP measurements were related to MCI, which was
      independently associated with nocturnal PP (odds ratio (OR) = 2.552, 95% CI
      1.137, 5.728) and also related to the presence of deep white matter
      hyperintensities (OR = 1.903, 1.096, 3.306). Therefore, higher day and night
      ambulatory PP measurements are associated with poor cognitive outcomes.

PMID- 25966946
TI  - CX3CL1/CX3CR1-mediated microglia activation plays a detrimental role in ischemic
      mice brain via p38MAPK/PKC pathway.
AB  - The exact roles of activated microglia and fractalkine (CX3CL1)/fractalkine
      receptor (CX3CR1) signaling are not fully understood in brain ischemic injury and
      the findings reported are controversial. Here, we investigated the effects of
      CX3CR1 siRNA on the expression of CX3CR1, p38 mitogen-activated protein kinase
      (p38MAPK), Protein Kinase C (PKC) and inflammatory cytokines, microglia
      activation, white matter lesions, and cognitive function in mice treated with
      bilateral common carotid artery stenosis (BCAS) in vivo as well as effects of
      exogenous CX3CL1, CX3CR1 siRNA, and SB2035080 on expression of inflammatory
      cytokines in BV2 microglia treated with oxygen-glucose deprivation (OGD) in
      vitro. We showed that CX3CR1 siRNA significantly inhibited the increased
      expression of CX3CR1, p38MAPK, PKC as well as tumor necrosis factor-alpha (TNF
      alpha), interleukin (IL)-1beta, and IL-6, and also attenuated microglia
      activation, white matter lesions, and cognitive deficits induced by BCAS in mice
      brain. We also showed that exogenous CX3CL1 could induce a further enhancement in
      TNF-alpha and IL-1beta expression, which could be suppressed by CX3CR1 siRNA or
      by the p38MAPK inhibitor in OGD-treated BV2 microglial cells in vitro. Our
      findings indicated that CX3CL1/CX3CR1-mediated microglial activation plays a
      detrimental role in ischemic brain via p38MAPK/PKC signaling and also suggested
      that CX3CL1/CX3CR1 axis might be a putative therapeutic target to disrupt the
      cascade of deleterious events that lead to brain ischemic injury. 

PMID- 25966947
TI  - Noninvasive quantification of cerebral metabolic rate for glucose in rats using
      (18)F-FDG PET and standard input function.
AB  - Measurement of arterial input function (AIF) for quantitative positron emission
      tomography (PET) studies is technically challenging. The present study aimed to
      develop a method based on a standard arterial input function (SIF) to estimate
      input function without blood sampling. We performed (18)F-fluolodeoxyglucose
      studies accompanied by continuous blood sampling for measurement of AIF in 11
      rats. Standard arterial input function was calculated by averaging AIFs from
      eight anesthetized rats, after normalization with body mass (BM) and injected
      dose (ID). Then, the individual input function was estimated using two types of
      SIF: (1) SIF calibrated by the individual's BM and ID (estimated individual input
      function, EIF(NS)) and (2) SIF calibrated by a single blood sampling as proposed
      previously (EIF(1S)). No significant differences in area under the curve (AUC) or
      cerebral metabolic rate for glucose (CMRGlc) were found across the AIF-, EIF(NS)
      , and EIF(1S)-based methods using repeated measures analysis of variance. In the
      correlation analysis, AUC or CMRGlc derived from EIF(NS) was highly correlated
      with those derived from AIF and EIF(1S). Preliminary comparison between AIF and
      EIF(NS) in three awake rats supported an idea that the method might be applicable
      to behaving animals. The present study suggests that EIF(NS) method might serve
      as a noninvasive substitute for individual AIF measurement. 

PMID- 25966949
TI  - Low-level light in combination with metabolic modulators for effective therapy of
      injured brain.
AB  - Vascular damage occurs frequently at the injured brain causing hypoxia and is
      associated with poor outcomes in the clinics. We found high levels of glycolysis,
      reduced adenosine triphosphate generation, and increased formation of reactive
      oxygen species and apoptosis in neurons under hypoxia. Strikingly, these adverse
      events were reversed significantly by noninvasive exposure of injured brain to
      low-level light (LLL). Low-level light illumination sustained the mitochondrial
      membrane potential, constrained cytochrome c leakage in hypoxic cells, and
      protected them from apoptosis, underscoring a unique property of LLL. The effect
      of LLL was further bolstered by combination with metabolic substrates such as
      pyruvate or lactate both in vivo and in vitro. The combinational treatment
      retained memory and learning activities of injured mice to a normal level,
      whereas other treatment displayed partial or severe deficiency in these cognitive
      functions. In accordance with well-protected learning and memory function, the
      hippocampal region primarily responsible for learning and memory was completely
      protected by combination treatment, in marked contrast to the severe loss of
      hippocampal tissue because of secondary damage in control mice. These data
      clearly suggest that energy metabolic modulators can additively or
      synergistically enhance the therapeutic effect of LLL in energy-producing
      insufficient tissue-like injured brain. 

PMID- 25966948
TI  - Cell tracking technologies for acute ischemic brain injury.
AB  - Stem cell therapy has showed considerable potential in the treatment of stroke
      over the last decade. In order that these therapies may be optimized, the
      relative benefits of growth factor release, immunomodulation, and direct tissue
      replacement by therapeutic stem cells are widely under investigation. Fundamental
      to the progress of this research are effective imaging techniques that enable
      cell tracking in vivo. Direct analysis of the benefit of cell therapy includes
      the study of cell migration, localization, division and/or differentiation, and
      survival. This review explores the various imaging tools currently used in
      clinics and laboratories, addressing image resolution, long-term cell monitoring,
      imaging agents/isotopes, as well as safety and costs associated with each
      technique. Finally, burgeoning tracking techniques are discussed, with emphasis
      on multimodal imaging. 

PMID- 25966950
TI  - Inhibition of histone methyltransferases SUV39H1 and G9a leads to neuroprotection
      in an in vitro model of cerebral ischemia.
AB  - Cerebral ischemia induces a complex transcriptional response with global changes
      in gene expression. It is essentially regulated by transcription factors as well
      as epigenetic players. While it is well known that the inhibition of
      transcriptionally repressive histone deacetylases leads to neuroprotection, the
      role of histone methyltransferases in the postischemic transcriptional response
      remains elusive. We investigated the effects of inhibition of the repressive H3K9
      histone methyltransferases SUV39H1 and G9a on neuronal survival, H3K9 promoter
      signatures and gene expression. Their inhibition either with the specific blocker
      chaetocin or by use of RNA interference promoted neuronal survival in oxygen
      glucose deprivation (OGD). Brain-derived neurotrophic factor (BDNF) was
      upregulated and BDNF promoter regions showed an increase in histone marks
      characteristic for active transcription. The BDNF blockade with K252a abrogated
      the protective effect of chaetocin treatment. In conclusion, inhibition of
      histone methyltransferases SUV39H1 and G9a confers neuroprotection in a model of
      hypoxic metabolic stress, which is at least in part mediated by BDNF. 

PMID- 25966951
TI  - Reduced blood flow in normal white matter predicts development of leukoaraiosis.
AB  - The purpose of this study was to investigate whether low cerebral blood flow
      (CBF) is associated with subsequent development of white matter hyperintensities
      (WMH). Patients were included from a longitudinal magnetic resonance (MR) imaging
      study of minor stroke/transient ischemic attack patients. Images were co
      registered and new WMH at 18 months were identified by comparing follow-up
      imaging with baseline fluid-attenuated inversion recovery (FLAIR). Regions-of
      interest (ROIs) were placed on FLAIR images in one of three categories: (1) WMH
      seen at both baseline and follow-up imaging, (2) new WMH seen only on follow-up
      imaging, and (3) regions of normal-appearing white matter at both time points.
      Registered CBF maps at baseline were used to measure CBF in the ROIs. A
      multivariable model was developed using mixed-effects logistic regression to
      determine the effect of baseline CBF on the development on new WMH. Forty
      patients were included. Mean age was 61+/-11 years, 30% were female. Low baseline
      CBF, female sex, and presence of diabetes were independently associated with the
      presence of new WMH on follow-up imaging. The odds of having new WMH on follow-up
      imaging reduces by 0.61 (95% confidence interval=0.57 to 0.65) for each 1 mL/100
      g per minute increase in baseline CBF. We conclude that regions of white matter
      with low CBF develop new WMH on follow-up imaging. 

PMID- 25966952
TI  - The effects of delayed reduction of tonic inhibition on ischemic lesion and
      sensorimotor function.
AB  - To aid in development of chronic stage treatments for sensorimotor deficits
      induced by ischemic stroke, we investigated the effects of GABA antagonism on
      brain structure and fine skilled reaching in a rat model of focal ischemia
      induced via cortical microinjections of endothelin-1 (ET-1). Beginning 7 days
      after stroke, animals were administered a gamma-aminobutyric acid (GABAA) inverse
      agonist, L-655,708, at a dose low enough to afford alpha5-GABAA receptor
      specificity. A week after stroke, the ischemic lesion comprised a small
      hypointense necrotic core (6+/-1 mm(3)) surrounded by a large (62+/-11 mm(3))
      hyperintense perilesional region; the skilled reaching ability on the Montoya
      staircase test was decreased to 34%+/-2% of the animals' prestroke performance
      level. On L-655,708 treatment, animals showed a progressive decrease in total
      stroke volume (13+/-4 mm(3) per week), with no change in animals receiving
      placebo. Concomitantly, treated animals' skilled reaching progressively improved
      by 9%+/-1% per week, so that after 2 weeks of treatment, these animals performed
      at 65%+/-6% of their baseline ability, which was 25%+/-11% better than animals
      given placebo. These data indicate beneficial effects of delayed, sustained low
      dose GABAA antagonism on neuroanatomic injury and skilled reaching in the chronic
      stage of stroke recovery in an ET-1 rat model of focal ischemia. 

PMID- 25966953
TI  - Erythropoietin dampens injury-induced microglial motility.
AB  - Traumatic brain injury causes progressive brain atrophy and cognitive decline.
      Surprisingly, an early treatment with erythropoietin (EPO) prevents these
      consequences of secondary neurodegeneration, but the mechanisms have remained
      obscure. Here we show by advanced imaging and innovative analytical tools that
      recombinant human EPO, a clinically established and neuroprotective growth
      factor, dampens microglial activity, as visualized also in vivo by a strongly
      attenuated injury-induced cellular motility. 

PMID- 25966955
TI  - Is forebrain neurogenesis a potential repair mechanism after stroke?
AB  - The use of adult subventricular zone (SVZ) neurogenesis as brain repair strategy
      after stroke represents a hot topic in neurologic research. Recent radiocarbon-14
      dating has revealed a lack of poststroke neurogenesis in the adult human
      neocortex; however, adult neurogenesis has been shown to occur, even under
      physiologic conditions, in the human striatum. Here, these results are contrasted
      with experimental poststroke neurogenesis in the murine brain. Both in humans and
      in rodents, the SVZ generates predominantly calretinin (CR)-expressing GABAergic
      interneurons, which cannot replace the broad spectrum of neuronal subtypes
      damaged by stroke. Therefore, SVZ neurogenesis may represent a repair mechanism
      only after genetic manipulation redirecting its differentiation. 

PMID- 25966954
TI  - Beta1-adrenergic receptor-mediated dilation of rat cerebral artery requires
      Shaker-type KV1 channels on PSD95 scaffold.
AB  - Postsynaptic density-95 (PSD95) is a scaffolding protein in cerebral vascular
      smooth muscle cells (cVSMCs), which binds to Shaker-type K(+) (KV1) channels and
      facilitates channel opening through phosphorylation by protein kinase A. beta1
      Adrenergic receptors (beta1ARs) also have a binding motif for PSD95. Functional
      association of beta1AR with KV1 channels through PSD95 may represent a novel
      vasodilator complex in cerebral arteries (CA). We explored whether a beta1AR
      PSD95-KV1 complex is a determinant of rat CA dilation. RT-PCR and western blots
      revealed expression of beta1AR in CA. Isoproterenol induced a concentration
      dependent dilation of isolated, pressurized rat CA that was blocked by the
      beta1AR blocker CGP20712. Cranial window imaging of middle cerebral arterioles in
      situ showed isoproterenol- and norepinephrine-induced dilation that was blunted
      by beta1AR blockade. Isoproterenol-induced hyperpolarization of cVSMCs in
      pressurized CA was blocked by CGP20712. Confocal images of cVSMCs immunostained
      with antibodies against beta1AR and PSD95 indicated strong colocalization, and
      PSD95 co-immunoprecipitated with beta1AR in CA lysate. Blockade of KV1 channels,
      beta1AR or disruption of PSD95-KV1 interaction produced similar blunting of
      isoproterenol-induced dilation in pressurized CA. These findings suggest that
      PSD95 mediates a vasodilator complex with beta1AR and KV1 channels in cVSMCs.
      This complex may be critical for proper vasodilation in rat CA. 

PMID- 25966956
TI  - Arginase I release from activated neutrophils induces peripheral
      immunosuppression in a murine model of stroke.
AB  - Transient suppression of peripheral immunity is a major source of complication
      for patients suffering from ischemic stroke. The release of Arginase I (ArgI)
      from activated neutrophils has recently been associated with T-cell dysfunction
      in a number of pathologies. However, this pathway has not been previously
      explored in ischemic stroke. Using the murine model of transient middle cerebral
      artery occlusion, we explored effects of stroke on peripheral T-cell function and
      evaluated the role of neutrophils and ArgI. Stimulation of splenic T cells from
      post-stroke animals with anti-CD3/CD28 resulted in decreased proliferation and
      interferon-gamma production when compared with sham-surgery controls. Flow
      cytometric analysis of intrasplenic leukocytes exposed the presence of a
      transient population of activated neutrophils that correlated quantitatively with
      elevated ArgI levels in culture media. In vitro activation of purified resting
      neutrophils from unmanipulated controls confirmed the capacity for murine
      neutrophils to release ArgI from preformed granules. We observed decreased
      expression of the L-arg-sensitive CD3zeta on T cells, consistent with decreased
      functional activity. Critically, L-arg supplementation restored the functional
      response of post-stroke T cells to mitogenic stimulation. Together, these data
      outline a novel mechanism of reversible, neutrophil-mediated peripheral
      immunosuppression related to ArgI release following ischemic stroke. 

PMID- 25966957
TI  - Eccentricity mapping of the human visual cortex to evaluate temporal dynamics of
      functional T1rho mapping.
AB  - Recent experiments suggest that T1 relaxation in the rotating frame (T(1rho)) is
      sensitive to metabolism and can detect localized activity-dependent changes in
      the human visual cortex. Current functional magnetic resonance imaging (fMRI)
      methods have poor temporal resolution due to delays in the hemodynamic response
      resulting from neurovascular coupling. Because T(1rho) is sensitive to factors
      that can be derived from tissue metabolism, such as pH and glucose concentration
      via proton exchange, we hypothesized that activity-evoked T(1rho) changes in
      visual cortex may occur before the hemodynamic response measured by blood
      oxygenation level-dependent (BOLD) and arterial spin labeling (ASL) contrast. To
      test this hypothesis, functional imaging was performed using T(1rho), BOLD, and
      ASL in human participants viewing an expanding ring stimulus. We calculated
      eccentricity phase maps across the occipital cortex for each functional signal
      and compared the temporal dynamics of T(1rho) versus BOLD and ASL. The results
      suggest that T(1rho) changes precede changes in the two blood flow-dependent
      measures. These observations indicate that T(1rho) detects a signal distinct from
      traditional fMRI contrast methods. In addition, these findings support previous
      evidence that T(1rho) is sensitive to factors other than blood flow, volume, or
      oxygenation. Furthermore, they suggest that tissue metabolism may be driving
      activity-evoked T(1rho) changes.

PMID- 25966958
TI  - Comparison of porcine anti-human lymphocyte globulin and rabbit anti-human
      thymocyte globulin in the treatment of severe aplastic anemia: a retrospective
      single-center study.
AB  - OBJECTIVES: To compare the safety and efficacy of porcine antilymphocyte globulin
      (pALG) and rabbit antithymocyte globulin (rATG) in treating severe aplastic
      anemia (SAA). METHODS: Seventy-seven patients with SAA that received
      immunosuppressive therapy between July 2004 and December 2013 at the Department
      of Hematology, the Second Affiliated Hospital of Xi'an Jiaotong University, were
      retrospectively analyzed. Forty-five patients received treatment including pALG
      (pALG group), and 32 patients received treatment including rATG (rATG group).
      Effective treatment rates between the two groups 1 yr after the treatment were
      compared; Kaplan-Meier 5-yr survival curve and log-rank test compared survival
      rates between the groups. All adverse responses were recorded. RESULTS: The 1-yr
      overall response rate in the pALG group (83.78%) was significantly higher than
      that in the rATG group (66.67%, P = 0.036), and the 5-yr overall survival rate in
      the pALG group (82.22%) was also higher than that in the rATG group (68.75%), but
      the difference was not statistically significant (P = 0.32). The incidence of
      adverse events was similar in the two groups, and no treatment-related deaths
      occurred. CONCLUSIONS: The efficacies, survival, and safety profiles of pALG
      based treatments are similar to or even better than those of rATG-based
      treatments. These results may help guide the clinical use of pALG in
      immunosuppressive therapy for SAA.

PMID- 25966959
TI  - Transverse cervical vessels as recipient vessels in oral and maxillofacial
      microsurgical reconstruction after former operations with or without
      radiotherapy.
AB  - BACKGROUND: The purpose of this study was to investigate the reliability and
      outcome of using the transverse cervical vessel (TCV) as a recipient vessel for
      microvascular reconstruction in patients whose vessels in the neck region are
      unavailable because of previous surgery or radiotherapy. METHODS: Between January
      2012 and August 2014, secondary head and neck reconstruction was performed using
      the TCV as a recipient vessel in eight patients who had undergone previous neck
      dissection and radiation therapy (n = 5). Five patients had a recurrent
      carcinoma, one had undergone an operation for scar release and two had been
      treated surgically for a second primary cancer. The anterolateral thigh flap
      (ALT), anteromedial thigh flap (AMT), and fibular flap were used for the
      reconstruction. Clinical data were recorded for each patient. RESULTS: All of the
      ipsilateral transverse cervical arteries were found to be free of disease. The
      second free flap was revascularized using the TCVs (n = 6) or the external (n =
      1) or internal (n = 1) jugular vein. The free flaps used for the reconstruction
      included the ALT flap (n = 6), AMT flap (n = 2), and fibular flap (n = 1). All of
      the flaps survived without vascular events, and the patients healed without major
      complications. The mean follow-up time was 11 months. One patient died of distant
      metastases during follow-up. CONCLUSIONS: In patients who have previously
      undergone neck surgery with or without radiotherapy, the TCVs are reliable and
      easily accessible recipient vessels for microsurgical reconstruction in the oral
      and maxillofacial region. If the transverse cervical vein is unavailable, the
      internal or external jugular vein should be dissected carefully to serve as an
      alternative for microvascular anastomoses.

PMID- 25966960
TI  - Rituximab preserves vision in ocular mucous membrane pemphigoid.
AB  - OBJECTIVE: To study the effectiveness and safety of anti-CD20 B-cell antibody
      rituximab (RTX) in the treatment of ocular mucous membrane pemphigoid (MMP).
      METHODS: Retrospective analysis of six MMP patients receiving RTX with or without
      concomitant immunosuppression. RTX was administered as a high dose regimen (1000
      mg/infusion, day 0 and day 14/cycle). Five patients received more than one cycle.
      Main outcome measure was the treatment response, defined as complete remission
      (CR) or partial remission (PR), monitored at 16 and 24 weeks. As secondary
      outcome measure, drug-related adverse events were evaluated. RESULTS: All
      patients responded within 16 weeks. Initial treatment response vanished in five
      of six patients at a mean of 10 months (+/- 4.4 standard deviation [SD]). A
      second cycle was initiated thereafter (interval 12 months +/- 6.4 SD) resulting
      in CR in two of five and PR in three of five patients. One patient stabilized
      only when additional immunosuppression was initiated. Mean follow up was 22
      months (+/- 8.2 SD).Two individuals experienced infusion reactions. CONCLUSIONS:
      Our study adds long-term data to the very limited experience with biologicals in
      MMP, indicating that RTX is a promising option for patients with advanced
      disease. We report for the first time the high dose regimen of RTX applied in a
      consecutive series.

PMID- 25966961
TI  - Bioinformatics analysis of circulating cell-free DNA sequencing data.
AB  - The discovery of cell-free DNA molecules in plasma has opened up numerous
      opportunities in noninvasive diagnosis. Cell-free DNA molecules have become
      increasingly recognized as promising biomarkers for detection and management of
      many diseases. The advent of next generation sequencing has provided
      unprecedented opportunities to scrutinize the characteristics of cell-free DNA
      molecules in plasma in a genome-wide fashion and at single-base resolution.
      Consequently, clinical applications of circulating cell-free DNA analysis have
      not only revolutionized noninvasive prenatal diagnosis but also facilitated
      cancer detection and monitoring toward an era of blood-based personalized
      medicine. With the remarkably increasing throughput and lowering cost of next
      generation sequencing, bioinformatics analysis becomes increasingly demanding to
      understand the large amount of data generated by these sequencing platforms. In
      this Review, we highlight the major bioinformatics algorithms involved in the
      analysis of cell-free DNA sequencing data. Firstly, we briefly describe the
      biological properties of these molecules and provide an overview of the general
      bioinformatics approach for the analysis of cell-free DNA. Then, we discuss the
      specific upstream bioinformatics considerations concerning the analysis of
      sequencing data of circulating cell-free DNA, followed by further detailed
      elaboration on each key clinical situation in noninvasive prenatal diagnosis and
      cancer management where downstream bioinformatics analysis is heavily involved.
      We also discuss bioinformatics analysis as well as clinical applications of the
      newly developed massively parallel bisulfite sequencing of cell-free DNA.
      Finally, we offer our perspectives on the future development of bioinformatics in
      noninvasive diagnosis. 

PMID- 25966962
TI  - Diabetes, obesity, and recommended fruit and vegetable consumption in relation to
      food environment sub-types: a cross-sectional analysis of Behavioral Risk Factor
      Surveillance System, United States Census, and food establishment data.
AB  - BACKGROUND: Social and spatial factors are an important part of individual and
      community health. The objectives were to identify food establishment sub-types
      and evaluate prevalence of diabetes, obesity, and recommended fruit and vegetable
      consumption in relation to these sub-types in the Washington DC metropolitan
      area. METHODS: A cross-sectional study design was used. A measure of retail food
      environment was calculated as the ratio of number of sources of unhealthier food
      options (fast food, convenience stores, and pharmacies) to healthier food options
      (grocery stores and specialty food stores). Two categories were created: <= 1.0
      (healthier options) and > 1.0 (unhealthier options). k-means clustering was used
      to identify clusters based on proportions of grocery stores, restaurants,
      specialty food, fast food, convenience stores, and pharmacies. Prevalence data
      for county-level diabetes, obesity, and consumption of five or more fruits or
      vegetables per day (FV5) was obtained from the Behavioral Risk Factor
      Surveillance System. Multiple imputation was used to predict block-group level
      health outcomes with US Census demographic and economic variables as the inputs.
      RESULTS: The healthier options category clustered into three sub-types: 1)
      specialty food, 2) grocery stores, and 3) restaurants. The unhealthier options
      category clustered into two sub-types: 1) convenience stores, and 2) restaurants
      and fast food. Within the healthier options category, diabetes prevalence in the
      sub-types with high restaurants (5.9 %, p = 0.002) and high specialty food (6.1
      %, p = 0.002) was lower than the grocery stores sub-type (7.1 %). The high
      restaurants sub-type compared to the high grocery stores sub-type had
      significantly lower obesity prevalence (28.6 % vs. 31.2 %, p < 0.001) and higher
      FV5 prevalence (25.2 % vs. 23.1 %, p < 0.001). Within the larger unhealthier
      options category, there were no significant differences in diabetes, obesity, or
      higher FV5 prevalence across the two sub-types. However, restaurants (including
      fast food) sub-type was significantly associated with lower diabetes and obesity,
      and higher FV prevalence compared to grocery store sub-type. CONCLUSIONS: These
      results suggest that there are sub-types within larger categories of food
      environments that are differentially associated with adverse health outcomes.
      These observations support the specific food establishment composition of an area
      may be an important component of the food establishment-health relationship.

PMID- 25966964
TI  - Transcatheter aortic valve implantation--update and evidence.
AB  - Transcatheter aortic valve implantation (T-AVI) has become the standard of care
      for high-risk patients suffering from severe aortic valve stenosis. More than
      60,000 implants have been performed to date. While the first-generation T-AVI
      devices had some specific issues, the advancements in these first-generation
      devices and the development of second-generation devices significantly reduced
      the incidence of peri-procedural complications. The two major access routes are
      the transfemoral (TF) and the transapical (TA) approach. Both approaches have
      their advantages and should be considered equal alternatives for finding the best
      treatment option for the individual patient. Currently there are discussions
      about extending the indication to patients with lower risk profiles. However,
      there is no real evidence to justify an expansion, as results of surgical aortic
      valve replacement in low and intermediate risk patients are excellent. 

PMID- 25966963
TI  - Relationship between the risk for a shrimp allergy and freshness or cooking.
AB  - Tropomyosins are defined as risk factors for shrimp allergy. However, their
      concentration in different preparations has not been clarified. We quantified the
      tropomyosin concentration in shrimp meat, which was cooked using several methods
      or was stored under various conditions. The results demonstrated that shrimp meat
      from various preparations and storage conditions maintained tropomyosin
      concentrations that were sufficient to cause food allergies. 

PMID- 25966965
TI  - Triphala in prevention of dental caries and as an antimicrobial in oral cavity- a
      review.
AB  - Dental caries is a widely prevalent infectious disease afflicting the humans
      worldwide. Each year oral infections such as dental caries, periodontal diseases
      and oral candidiasis significantly adds to the economic burden of the world.
      Though there are standard management techniques for these diseases; they do have
      side effects and are not cost effective. Ayurveda is a traditional Indian system
      of medicine that is being practiced in the Indian peninsula since ages. Among the
      various herbal medicines in ayurveda, triphala occupies a royal position due to
      its wide beneficial systemic actions. Triphala is a mixture of fruits of
      Terminalia bellirica, Terminalia chebula and Emblica officinalis. The
      antimicrobial actions of triphala are well documented in the literature. However
      availability of review articles regarding triphala as an antimicrobial against
      oral infections is limited. Need was felt to review this aspect of triphala. The
      present article reviews the use of triphala and its constituents in the
      prevention and control of dental caries and other common oral infections.
      Thorough review of the literature indicated that triphala can be effectively used
      to manage dental caries, gingival and periodontal diseases. Further it can also
      be utilized as a root canal irrigant and against oral candida species. 

PMID- 25966966
TI  - Clustered ribbed-nanoneedle structured copper surfaces with high-efficiency
      dropwise condensation heat transfer performance.
AB  - We report that the dropwise condensation heat transfer (DCHT) effectiveness of
      copper surfaces can be dramatically enhanced by in situ grown clustered ribbed
      nanoneedles. Combined experiments and theoretical analyses reveal that, due to
      the microscopically rugged and low-adhesive nature of building blocks, the
      nanosamples can not only realize high-density nucleation but constrain growing
      condensates into suspended microdrops via the self-transport and/or self
      expansion mode for subsequently self-propelled jumping, powered by coalescence
      released excess surface energy. Consequently, our nanosample exhibits over 125%
      enhancement in DCHT coefficient. This work helps develop advanced heat-transfer
      materials and devices for efficient thermal management and energy utilization. 

PMID- 25966967
TI  - The evolution of relative brain size in marsupials is energetically constrained
      but not driven by behavioral complexity.
AB  - Evolutionary increases in mammalian brain size relative to body size are
      energetically costly but are also thought to confer selective advantages by
      permitting the evolution of cognitively complex behaviors. However, many
      suggested associations between brain size and specific behaviors - particularly
      related to social complexity - are possibly confounded by the reproductive
      diversity of placental mammals, whose brain size evolution is the most frequently
      studied. Based on a phylogenetic generalized least squares analysis of a data set
      on the reproductively homogenous clade of marsupials, we provide the first
      quantitative comparison of two hypotheses based on energetic constraints
      (maternal investment and seasonality) with two hypotheses that posit behavioral
      selection on relative brain size (social complexity and environmental
      interactions). We show that the two behavioral hypotheses have far less support
      than the constraint hypotheses. The only unambiguous associates of brain size are
      the constraint variables of litter size and seasonality. We also found no
      association between brain size and specific behavioral complexity categories
      within kangaroos, dasyurids, and possums. The largest-brained marsupials after
      phylogenetic correction are from low-seasonality New Guinea, supporting the
      notion that low seasonality represents greater nutrition safety for brain
      maintenance. Alternatively, low seasonality might improve the maternal support of
      offspring brain growth. The lack of behavioral brain size associates, found here
      and elsewhere, supports the general 'cognitive buffer hypothesis' as the best
      explanatory framework of mammalian brain size evolution. However, it is possible
      that brain size alone simply does not provide sufficient resolution on the
      question of how brain morphology and cognitive capacities coevolve.

PMID- 25966968
TI  - Continuous Traumatic Situations in the Face of Ongoing Political Violence: The
      Relationship Between CTS and PTSD.
AB  - This article presents a literature review of the concept of continuous traumatic
      situations (CTS), which relates to residents living in ongoing situations of
      political violence and national security threats. The first aim of this review is
      to narrow the gap regarding knowledge about the concept of CTS by presenting
      findings from studies that have assessed the effects of CTS on civilian
      populations. The second aim is to describe CTS in a way that highlights the
      differences and similarities between posttraumatic stress disorder and responses
      to CTS. This distinction is a necessary precondition for examining CTS, as is a
      careful clinical analysis of the development and course of symptoms. This
      literature review also highlights the importance of adopting a supplementary
      perspective for understanding the psychological impact of ongoing exposure to
      real threats, which can be used as a basis for developing intervention strategies
      that are appropriate for coping with life in the context of persistent violence.
      CTS can be manifested as emotions, behaviors, and perceptions among individuals,
      families, communities, and societies. The nature of the proposed model of CTS is
      a circular one, combining past and future perceptions and emotional reactions
      that have resulted from continuous and repeated traumatic experiences over an
      extended period of time. This wider understanding reflects the complexity of the
      CTS phenomenon. Various micro and macro interventions relating to CTS as the
      result of political violence situations and national security threats are
      presented, and recommendations for practice, policy, and future research are
      offered.

PMID- 25966969
TI  - Enhancing the Impact of Family Justice Centers via Motivational Interviewing: An
      Integrated Review.
AB  - The Family Justice Center (FJC) model is an approach to assisting survivors of
      intimate partner violence (IPV) that focuses on integration of services under one
      roof and co-location of staff members from a range of multidisciplinary agencies.
      Even though the FJC model is touted as a best practice strategy to help IPV
      survivors, empirical support for the effectiveness of this approach is scarce.
      The current article consolidates this small yet promising body of empirically
      based literature in a clinically focused review. Findings point to the importance
      of integrating additional resources into the FJC model to engage IPV survivors
      who have ambivalent feelings about whether to accept help, leave the abusive
      relationship, and/or participate in criminal justice processes to hold the
      offender accountable. One such resource, motivational interviewing (MI), holds
      promise in aiding IPV survivors with these decisions, but empirical investigation
      into how MI can be incorporated into the FJC model has yet to be published. This
      article, therefore, also integrates the body of literature supporting the FJC
      model with the body of literature supporting MI with IPV survivors. Implications
      for practice, policy, and research are incorporated throughout this review.

PMID- 25966970
TI  - Agmatine, by Improving Neuroplasticity Markers and Inducing Nrf2, Prevents
      Corticosterone-Induced Depressive-Like Behavior in Mice.
AB  - Agmatine, an endogenous neuromodulator, is a potential candidate to constitute an
      adjuvant/monotherapy for the management of depression. A recent study by our
      group demonstrated that agmatine induces Nrf2 and protects against corticosterone
      effects in a hippocampal neuronal cell line. The present study is an extension of
      this previous study by assessing the antidepressant-like effect of agmatine in an
      animal model of depression induced by corticosterone in mice. Swiss mice were
      treated simultaneously with agmatine or imipramine at a dose of 0.1 mg/kg/day
      (p.o.) and corticosterone for 21 days and the daily administrations of
      experimental drugs were given immediately prior to corticosterone (20 mg/kg/day,
      p.o.) administrations. Wild-type C57BL/6 mice (Nrf2 (+/+)) and Nrf2 KO (Nrf2 (-/
      )) were treated during 21 days with agmatine (0.1 mg/kg/day, p.o.) or vehicle.
      Twenty-four hours after the last treatments, the behavioral tests and biochemical
      assays were performed. Agmatine treatment for 21 days was able to abolish the
      corticosterone-induced depressive-like behavior and the alterations in the
      immunocontent of mature BDNF and synaptotagmin I, and in the serotonin and
      glutamate levels. Agmatine also abolished the corticosterone-induced changes in
      the morphology of astrocytes and microglia in CA1 region of hippocampus. In
      addition, agmatine treatment in control mice increased noradrenaline, serotonin,
      and dopamine levels, CREB phosphorylation, mature BDNF and synaptotagmin I
      immunocontents, and reduced pro-BDNF immunocontent in the hippocampus. Agmatine's
      ability to produce an antidepressant-like effect was abolished in Nrf2 (-/-)
      mice. The present results reinforce the participation of Nrf2 in the
      antidepressant-like effect produced by agmatine and expand literature data
      concerning its mechanisms of action.

PMID- 25966972
TI  - Positron Emission Tomography/Computed Tomography for the Pleural Staging of
      Malignant Pleural Mesothelioma: How Accurate Is It?
AB  - BACKGROUND: Careful clinical staging in patients with malignant pleural
      mesothelioma (MPM) is fundamental in management planning. Positron emission
      tomography/computed tomography (PET/CT) is increasingly recognized as an
      important staging modality. OBJECTIVES: The purpose of this study was to assess
      whether the metabolic activity of the pleural tumor detected with PET/CT
      correlates with specific endoscopic features and pleural distribution of the
      lesions as assessed by medical thoracoscopy. METHODS: Consecutive patients with
      MPM and available PET/CT performed before thoracoscopy were separated into 2
      groups, according to their standardized uptake value (SUV). Kaplan-Meier-analysis
      for survival was performed on groups with low and high SUV. Agreement between
      PET/CT and thoracoscopy evaluation was analyzed using Cohen's kappa coefficient.
      The Wilcoxon test was used to compare the median SUV, and the chi(2) test was
      used to evaluate differences in endoscopic findings. RESULTS: A total of 32
      patients were included. The median maximum SUV (SUV max) was 6.1 and patients
      were separated into 2 groups based on this cutoff. Patients with SUV max <6.1 had
      a better survival than those with SUV max >=6.1 (p = 0.005). The comparison
      between PET/CT and thoracoscopy showed a fair agreement for visceral and
      diaphragmatic pleural involvement and moderate agreement for the presence of
      nodular lesions. There was a statistically significant association between median
      SUV max and visceral pleural involvement; nodular lesions and visceral pleural
      involvement were more common in the high-SUV group than in the low-SUV group (p =
      0.0012 and p = 0.03, respectively). CONCLUSIONS: PET/CT data may be predictive of
      thoracoscopic features of MPM associated with prognosis and staging, but the
      correlation is moderate at best. A degree of disagreement exists between these
      two modalities, which supports thoracoscopy as the gold standard for assessment
      of local invasion in MPM.

PMID- 25966973
TI  - Estuarine fish communities respond to climate variability over both river and
      ocean basins.
AB  - Estuaries are dynamic environments at the land-sea interface that are strongly
      affected by interannual climate variability. Ocean-atmosphere processes propagate
      into estuaries from the sea, and atmospheric processes over land propagate into
      estuaries from watersheds. We examined the effects of these two separate climate
      driven processes on pelagic and demersal fish community structure along the
      salinity gradient in the San Francisco Estuary, California, USA. A 33-year data
      set (1980-2012) on pelagic and demersal fishes spanning the freshwater to marine
      regions of the estuary suggested the existence of five estuarine salinity fish
      guilds: limnetic (salinity = 0-1), oligohaline (salinity = 1-12), mesohaline
      (salinity = 6-19), polyhaline (salinity = 19-28), and euhaline (salinity = 29
      32). Climatic effects propagating from the adjacent Pacific Ocean, indexed by the
      North Pacific Gyre Oscillation (NPGO), affected demersal and pelagic fish
      community structure in the euhaline and polyhaline guilds. Climatic effects
      propagating over land, indexed as freshwater outflow from the watershed (OUT),
      affected demersal and pelagic fish community structure in the oligohaline,
      mesohaline, polyhaline, and euhaline guilds. The effects of OUT propagated
      further down the estuary salinity gradient than the effects of NPGO that
      propagated up the estuary salinity gradient, exemplifying the role of variable
      freshwater outflow as an important driver of biotic communities in river
      dominated estuaries. These results illustrate how unique sources of climate
      variability interact to drive biotic communities and, therefore, that climate
      change is likely to be an important driver in shaping the future trajectory of
      biotic communities in estuaries and other transitional habitats. 

PMID- 25966974
TI  - Highly Stable, Protein-Resistant Surfaces via the Layer-by-Layer Assembly of
      Poly(sulfobetaine methacrylate) and Tannic Acid.
AB  - Zwitterionic materials have received great attention because of the non-fouling
      property. As a result of the electric neutrality of zwitterionic polymers, their
      layer-by-layer (LBL) assembly is generally conducted under specific conditions,
      such as very low pH values or ionic strength. The formed multilayers are unstable
      at high pH or in a high ionic strength environment. Therefore, the formation of
      highly stable multilayers of zwitterionic polymers via the LBL assembly process
      is still challenging. Here, we report the LBL assembly of poly(sulfobetaine
      methacrylate) (PSBMA) with a polyphenol, tannic acid (TA), for protein-resistant
      surfaces. The assembly process was monitored by a quartz crystal microbalance
      (QCM) and variable-angle spectroscopic ellipsometry (VASE), which confirms the
      formation of thin multilayer films. We found that the (TA/PSBMA)n multilayers are
      stable over a wide pH range of 4-10 and in saline, such as 1 M NaCl or urea
      solution. The surface morphology and chemical composition were characterized by
      specular reflectance Fourier transform infrared spectroscopy (FTIR/SR), X-ray
      photoelectron spectroscopy (XPS), and atomic force microscopy (AFM). Furthermore,
      (TA/PSBMA)n multilayers show high hydrophilicity, with a water contact angle
      lower than 15 degrees . A QCM was used to record the dynamic protein adsorption
      process. Adsorption amounts of bovine serum albumin (BSA), lysozyme (Lys), and
      hemoglobin (Hgb) on (TA/PSBMA)20 multilayers decreased to 0.42, 52.9, and 37.9
      ng/cm(2) from 328, 357, and 509 ng/cm(2) on a bare gold chip surface,
      respectively. In addition, the protein-resistance property depends upon the
      outmost layer. This work provides new insights into the LBL assembly of
      zwitterionic polymers. 

PMID- 25966975
TI  - The search for endocarditis in patients with candidemia: a systematic
      recommendation for echocardiography? A prospective cohort.
AB  - Most current guidelines do not recommend systematic screening with
      echocardiography in patients with candidemia, as Candida infective endocarditis
      (CIE) is considered an uncommon disease. During the study period, we recommended
      echocardiography systematically to all candidemic patients that did not have
      contraindications and accepted to participate in the study. We intended to assess
      the incidence of unrecognized CIE in adult patients with candidemia. Our
      institution is a tertiary teaching hospital in which we follow all patients with
      candidemia. From January 2007 to October 2012, echocardiography was
      systematically recommended to suitable candidates. We recorded 263 cases of
      candidemia in adult patients. Echocardiography was not performed in 76 of these
      patients for the following reasons: patients had died when blood cultures became
      positive (17), patients were critically or terminally ill (38), or the patient or
      physician refused the procedure (21). The remaining 187 patients constitute the
      basis of this report. CIE was diagnosed in 11 cases (4.2 % of the whole
      candidemic population and 5.9 % of the population with echocardiographic study).
      The results of transthoracic echocardiography (TTE) suggested infective
      endocarditis (IE) in 5/172 patients (2.9 %), and the result of transesophageal
      echocardiography (TEE) was positive in 10/87 (11.5 %). Among 11 confirmed cases
      of CIE, the disease was clinically unsuspected in three patients. At least 4.2 %
      of all candidemic patients have CIE. CIE is frequently clinically unsuspected and
      echocardiography is required to demonstrate a high proportion of cases. 

PMID- 25966971
TI  - Oligodendroglia and Myelin in Neurodegenerative Diseases: More Than Just
      Bystanders?
AB  - Oligodendrocytes, the myelinating cells of the central nervous system, mediate
      rapid action potential conduction and provide trophic support for axonal as well
      as neuronal maintenance. Their progenitor cell population is widely distributed
      in the adult brain and represents a permanent cellular reservoir for
      oligodendrocyte replacement and myelin plasticity. The recognition of
      oligodendrocytes, their progeny, and myelin as contributing factors for the
      pathogenesis and the progression of neurodegenerative disease has recently
      evolved shaping our understanding of these disorders. In the present review, we
      aim to highlight studies on oligodendrocytes and their progenitors in
      neurodegenerative diseases. We dissect oligodendroglial biology and illustrate
      evolutionary aspects in regard to their importance for neuronal functionality and
      maintenance of neuronal circuitries. After covering recent studies on
      oligodendroglia in different neurodegenerative diseases mainly in view of their
      function as myelinating cells, we focus on the alpha-synucleinopathy multiple
      system atrophy, a prototypical disorder with a well-defined oligodendroglial
      pathology.

PMID- 25966976
TI  - Cafeteria diet-fed mice is a pertinent model of obesity-induced organ damage: a
      potential role of inflammation.
AB  - OBJECTIVE: This study is aimed at evaluating the effects of a cafeteria diet
      (obesity) mouse model on early multi-organ functional, structural, endocrine and
      biochemical alterations. MATERIALS AND METHODS: Multi-organ damage is assessed
      using clinical, biochemical, pathological, and inflammatory parameters in 30 mice
      fed one of the three diets for 15 weeks: standard chow diet (SC), high fat (HF),
      or "Cafeteria diet" (CAF) (standard SC and a choice of highly palatable human
      cafeteria foods: chocolate, biscuits, and peanut butter). RESULTS: CAF diet was
      associated with an increase in body weight, energy intake, and serum cholesterol
      levels compared to the other diets, as well as higher insulin levels and lower
      glucose tolerance. Additionally, consumption of the CAF diet was associated with
      significantly higher weight gain, abdominal fat, and serum IL-6 levels, as well
      as more damage in the heart (coronary perivascular fibrosis and steatosis),
      kidney (chronic interstitial inflammation and glomerular sclerosis), and liver
      (liver weight, portal fibrosis, apoptosis, and steatosis) compared to the HF
      diet. CONCLUSION: Functional and structural damage in CAF were higher than HF of
      similar macronutrient composition. This study provides a novel dietary model in
      mice that mimics multi-organ physiologic alterations in humans secondary to
      obesity.

PMID- 25966977
TI  - Polyglycine hydrolases: Fungal beta-lactamase-like endoproteases that cleave
      polyglycine regions within plant class IV chitinases.
AB  - Polyglycine hydrolases are secreted fungal proteases that cleave glycine-glycine
      peptide bonds in the inter-domain linker region of specific plant defense
      chitinases. Previously, we reported the catalytic activity of polyglycine
      hydrolases from the phytopathogens Epicoccum sorghi (Es-cmp) and Cochliobolus
      carbonum (Bz-cmp). Here we report the identity of their encoding genes and the
      primary amino acid sequences of the proteins responsible for these activities.
      Peptides from a tryptic digest of Es-cmp were analyzed by LC-MS/MS and the
      spectra obtained were matched to a draft genome sequence of E. sorghi. From this
      analysis, a 642 amino acid protein containing a predicted beta-lactamase
      catalytic region of 280 amino acids was identified. Heterologous strains of the
      yeast Pichia pastoris were created to express this protein and its homolog from
      C. carbonum from their cDNAs. Both strains produced recombinant proteins with
      polyglycine hydrolase activity as shown by SDS-PAGE and MALDI-MS based assays.
      Site directed mutagenesis was used to mutate the predicted catalytic serine of Es
      cmp to glycine, resulting in loss of catalytic activity. BLAST searching of
      publicly available fungal genomes identified full-length homologous proteins in
      11 other fungi of the class Dothideomycetes, and in three fungi of the related
      class Sordariomycetes while significant BLAST hits extended into the phylum
      Basidiomycota. Multiple sequence alignment led to the identification of a network
      of seven conserved tryptophans that surround the beta-lactamase-like region. This
      is the first report of a predicted beta-lactamase that is an endoprotease. 

PMID- 25966978
TI  - Adenosine A2B receptor stimulates angiogenesis by inducing VEGF and eNOS in human
      microvascular endothelial cells.
AB  - Angiogenesis is critical to wound repair due to its role in providing oxygen and
      nutrients that are required to support the growth and function of reparative
      cells in damaged tissues. Adenosine receptors are claimed to be of paramount
      importance in driving wound angiogenesis by inducing VEGF. However, the
      underlying mechanisms for the regulation of adenosine receptors in VEGF as well
      as eNOS remain poorly understood. In the present study, we found that adenosine
      and the non-selective adenosine receptor agonists (NECA) induced tube formation
      in HMEC-1 in a dose-dependent manner. Adenosine or NECA (10 umol/L) significantly
      augmented the number and length of the segments in comparison with the control.
      Simultaneously, VEGF and eNOS were significantly upregulated following the
      administration of 10 umol/L NECA, while they were suppressed after A2B AR genetic
      silencing and pharmacological inhibition by MRS1754. In addition, VEGF expression
      and eNOS bioavailability elimination significantly reduced the formation of
      capillary-like structures. Furthermore, the activation of A2B AR by NECA
      significantly increased the intracellular cAMP levels and concomitant CREB
      phosphorylation, eventually leading to the production of VEGF in HMEC-1. However,
      the activated PKA-CREB pathway seemed to be invalidated in the induction of eNOS.
      Moreover, we found that the elicited PI3K/AKT signaling in response to the
      induction of NECA assisted in regulating eNOS but failed to impact on VEGF
      generation. In conclusion, the A2B AR activation-driven angiogenesis via cAMP-PKA
      CREB mediated VEGF production and PI3K/AKT-dependent upregulation of eNOS in HMEC
      1. 

PMID- 25966979
TI  - The cell cycle- and insulin-signaling-inhibiting miRNA expression pattern of very
      small embryonic-like stem cells contributes to their quiescent state.
AB  - Murine Oct4(+), very small embryonic-like stem cells (VSELs), are a quiescent
      stem cell population that requires a supportive co-culture layer to proliferate
      and/or to differentiate in vitro. Gene expression studies have revealed that the
      quiescence of these cells is due to changes in expression of parentally imprinted
      genes, including genes involved in cell cycle regulation and insulin and insulin
      like growth factor signaling (IIS). To investigate the role of microRNAs (miRNAs)
      in VSEL quiescence, we performed miRNA studies in highly purified VSELs and
      observed a unique miRNA expression pattern in these cells. Specifically, we
      observed significant differences in the expression of certain miRNA species
      (relative to a reference cell population), including (i) miRNA-25_1 and miRNA-19
      b, whose downregulation has the effect of upregulating cell cycle checkpoint
      genes and (ii) miRNA-675-3 p and miRNA-675-5 p, miRNA-292-5 p, miRNA-184, and
      miRNA-125 b, whose upregulation attenuates IIS. These observations are important
      for understanding the biology of these cells and for developing efficient ex vivo
      expansion strategies for VSELs isolated from adult tissues. 

PMID- 25966980
TI  - The effects of energy intake of four different feeding patterns in rats.
AB  - Energy intake can affect the metabolism. But it is not very clear that how and to
      what degree the metabolism can be changed by energy intake quantity and change.
      Here we applied four feeding patterns in male Sprague-Dawley rats--normal ad
      libitum diet (NFal), high-fat diet (HFal), caloric restriction (CR) after HFal
      (HFal-NFcr), and refeeding from CR to ad libitum (HFal-NFcr-NFal). Food intake
      and body weight, along with fat mass, insulin sensitivity, fasting plasma
      insulin, and glucose level were used to calculate the energy efficiency and
      compared the quantitative effects of energy intake. Energy intake changed little
      in NFal or HFal group; while it changed greatly and suddenly in HFal-NFcr or HFal
      NFcr-NFal group. All the parameters we detected were different between these four
      feeding patterns. Excess of energy intake from high-fat diet induced adverse
      outcomes with low energy efficiency. CR reversed the impairment of high-fat diet
      with very high energy efficiency in a short period. However, dramatic response
      with high energy efficiency induced by recovery to feeding ad libitum after CR,
      which was possible harmful to health. In conclusion, energy intake quantity and
      change are key determinants of metabolism. Different energy intake quantity and
      change affect body weight, white adipose tissue weight, insulin sensitivity, etc.
      at different degrees and speeds because of different energy efficiency.

PMID- 25966982
TI  - Bone marrow-derived fibrocytes contribute to liver fibrosis.
AB  - Chronic liver injury often leads to hepatic fibrosis, a condition associated with
      increased levels of circulating TGF-beta1 and lipopolysaccharide, activation of
      myofibroblasts, and extensive deposition of extracellular matrix, mostly collagen
      Type I. Hepatic stellate cells are considered to be the major(1) but not the only
      source of myofibroblasts in the injured liver.(2) Hepatic myofibroblasts may also
      originate from portal fibroblasts, mesenchymal cells, and fibrocytes.(3) Since
      the discovery of fibrocytes in 1994 by Dr. Bucala and colleagues, this bone
      marrow (BM)-derived collagen Type I-producing CD45(+) cells remain the most
      fascinating cells of the hematopoietic system. Due to the ability to
      differentiate into collagen Type I producing cells/myofibroblasts, fibrocytes
      were implicated in the pathogenesis of liver, skin, lung, and kidney fibrosis.
      However, studies of different organs often contain controversial results on the
      number of fibrocytes recruited to the site of injury and their biological
      function. Furthermore, fibrocytes were implicated in the pathogenesis of sepsis
      and were shown to possess antimicrobial activity. Finally, in response to
      specific stimuli, fibrocytes can give rise to fully differentiated macrophages,
      suggesting that in concurrence with the high plasticity of hematopoietic cells,
      fibrocytes exhibit progenitor properties. Here, we summarize our current
      understanding of the role of CD45(+)Collagen Type I(+) BM-derived cells in
      response to fibrogenic liver injury and septicemia and discuss the most recent
      evidence supporting the critical role of fibrocytes in the mediation of pro
      fibrogenic and/or pro-inflammatory responses.

PMID- 25966981
TI  - Dark Agouti rat model of chemotherapy-induced mucositis: establishment and
      current state of the art.
AB  - Mucositis is a major oncological problem. The entire gastrointestinal and
      genitourinary tract and also other mucosal surfaces can be affected in recipients
      of radiotherapy, and/or chemotherapy. Major progress has been made in recent
      years in understanding the mechanisms of oral and small intestinal mucositis,
      which appears to be more prominent than colonic damage. This progress is largely
      due to the development of representative laboratory animal models of mucositis.
      This review focuses on the development and establishment of the Dark Agouti rat
      mammary adenocarcinoma model by the Mucositis Research Group of the University of
      Adelaide over the past 20 years to characterize the mechanisms underlying
      methotrexate-, 5-fluorouracil-, and irinotecan-induced mucositis. It also aims to
      summarize the results from studies using different animal model systems to
      identify new molecular and cellular markers of mucositis.

PMID- 25966984
TI  - Re: Regulation of testicular descent.

PMID- 25966983
TI  - MicroRNAs targeting prostate cancer stem cells.
AB  - Prostate cancer is a frequently diagnosed cancer in males with high mortality in
      the world. As a heterogeneous tissue, the tumor mass contains a subpopulation
      that is called as cancer stem cells and displays stem-like properties such as
      self-renewal, epithelial-mesenchymal transition, metastasis, and drug resistance.
      Cancer stem cells have been identified in variant tumors and shown to be
      regulated by various molecules including microRNAs. MicroRNAs are a class of
      small non-coding RNAs, which can influence tumorigenesis via different
      mechanisms. In this review, we focus on the functions of microRNAs on regulating
      the stemness of prostate cancer stem cells with different mechanisms and propose
      the potential roles of microRNAs in prostate cancer therapy. 

PMID- 25966985
TI  - Negative pressure wound therapy in the treatment of ulcerated infantile
      haemangioma.
AB  - BACKGROUND: Infantile haemangioma is a common benign tumour of infancy.
      Ulceration is the most common complication and is often painful and difficult to
      treat. Propranolol therapy is widely used to induce involution in rapidly growing
      or ulcerated lesions, or those in anatomically awkward locations. The ideal
      dressing regimen for these lesions would provide effective analgesia, act as a
      wound dressing, and aid involution of the primary lesion. To date, no ideal
      regimen has been established. Negative pressure wound therapy (NPWT) has been
      used in adult and paediatric populations to help improve wound healing in a
      variety of settings. It may provide a useful alternative to traditional dressing
      regimens in ulcerated infantile haemangioma. METHODS: Six consecutive patients
      with ulcerating infantile haemangioma presenting to the Royal Children's Hospital
      vascular anomalies clinic were included in the study. Each patient was treated
      with a combination of NPWT and propranolol. Outcomes including time to wound
      healing, perceived ease of dressing management, and analgesia were recorded.
      RESULTS: Complete wound healing was obtained in all cases. Patient outcomes in
      terms of analgesia, comfort, and ease of wound dressing were improved following
      application of NPWT. DISCUSSION/CONCLUSIONS: We propose that this regimen
      represents a novel therapy for management of ulcerated infantile haemangioma.
      Possible mechanisms for healing effect, and improved analgesia are discussed.
      Further investigation is required to determine if negative pressure wound therapy
      results in faster healing times compared to traditional dressing regimens.

PMID- 25966987
TI  - How I treat T-cell acute lymphoblastic leukemia in adults.
AB  - T-cell immunophenotype of acute lymphoblastic leukemia (T-ALL) is an uncommon
      aggressive leukemia that can present with leukemic and/or lymphomatous
      manifestations. Molecular studies are enhancing our understanding of the
      pathogenesis of T-ALL, and the discovery of activating mutations of NOTCH1 and
      FBXW7 in a majority of patients has been a seminal observation. The use of
      pediatric intensive combination chemotherapy regimens in adolescents and young
      adults has significantly improved the outcome of patients with T-ALL. The use of
      nelarabine for relapsed and refractory T-ALL results in responses in a
      substantial minority of patients. Allogeneic hematopoietic cell transplantation
      (HCT) still plays a key role in patients with high-risk or relapsed/refractory
      disease. gamma-Secretase inhibitors hold promise for the treatment of patients
      with NOTCH1 mutations, and the results of clinical trials with these agents are
      eagerly awaited. It is recommended that younger patients receive a pediatric
      intensive regimen. Older and unfit patients can receive suitable multiagent
      chemotherapy and be allocated to HCT based on their response, risk factors, and
      comorbidities. Although advances in the treatment of T-ALL have lagged behind
      those of B-cell ALL, it is hoped that the molecular revolution will enhance our
      understanding of the pathogenesis and treatment of this aggressive lymphoid
      malignancy. 

PMID- 25966986
TI  - Frequency of coreceptor tropism in PBMC samples from HIV-1 recently infected
      blood donors by massively parallel sequencing: the REDS II study.
AB  - BACKGROUND: The interaction of HIV-1 and target cells involves sequential binding
      of the viral gp120 Env protein to the CD4 receptor and a chemokine co-receptor
      (either CCR5 or CXCR4). CCR5 antagonists have proved to be an effective salvage
      therapy in patients with CCR5 using variants (R5) but not with variants capable
      of using CXCR4 (*4) phenotype. Thus, it is critically important to determine
      cellular tropism of a country's circulating HIV strains to guide a management
      decision to improve treatment outcome. In this study, we report the prevalence of
      R5 and *4 HIV strains in 45 proviral DNA massively parallel sequencing "MPS" data
      from recently infected Brazilian blood donors. METHODS: The MPS data encompassing
      the tropism-related V3 loop region of the HIV-1 env gene was extracted from our
      recently published HIV-1 genomes sequenced by a paired-end protocol (Illumina).
      HIV-1 tropism was inferred using Geno2pheno[coreceptor] algorithm (3.5 % false
      positive rate). V3 net charge and 11/25 rules were also used for coreceptor
      prediction. RESULTS: Among the 45 samples for which tropism were determined, 39
      were exclusively R5 variants, 5 *4 variants, and one dual-tropic or mixed (D/M)
      populations of R5 and *4 viruses, corresponding to 86.7, 11.1 and 2.2 %,
      respectively. Thus, the proportion of all blood donors that harbor CXCR4-using
      virus was 13.3 % including individuals with D/M-tropic viruses. CONCLUSIONS: The
      presence of CCR5-tropic variants in more than 85 % of our cohort of
      antiretroviral-naive blood donors with recent HIV-1 infection indicates a
      potential benefit of CCR5 antagonists as a therapeutic option in Brazil.
      Therefore, determination of viral co-receptor tropism is an important diagnostic
      prerequisite.

PMID- 25966988
TI  - How I treat adults with relapsed or refractory Philadelphia chromosome-negative
      acute lymphoblastic leukemia.
AB  - The long-term prognosis of adult patients with relapsed Philadelphia chromosome
      negative acute lymphoblastic lymphoma (ALL) is poor. Allogeneic stem cell
      transplant in second remission is the only curative approach and is the goal when
      feasible. There is no standard chemotherapy regimen for relapsed disease,
      although a few agents are approved for use in this setting. The bispecific CD19
      directed CD3 T-cell engager, blinatumomab, has recently been granted accelerated
      approval by the US Food and Drug Administration for relapsed or refractory
      disease of B-cell lineage. For patients with relapsed T-cell ALL, nelarabine is
      available. Liposomal vincristine is also approved for relapsed disease. When
      selecting combination chemotherapy salvage options, evaluation of the prior
      treatment and timing of relapse informs treatment decisions. Monoclonal and
      cellular investigational therapies are quite promising and should be explored in
      the appropriate patient. 

PMID- 25966990
TI  - Project REENCONTRO: ethical aspects of genetic identification in families
      separated by the compulsory isolation of leprosy patients in Brazil.
AB  - In this paper, we discuss the experience of a team of geneticists, working in
      partnership with a Brazilian social movement aimed at promoting the rights of
      victims of Hansen's disease. These university researchers propose to use DNA test
      results to ascertain kinship connections and thereby reunite families that were
      sundered apart by draconian state policies of the mid-twentieth century that
      decreed the forced segregation of leprosy patients and the institutionalization
      of their children. The team's aim is to help revert stigma and reinforce positive
      group identity as well as to facilitate judicial claims to moral and financial
      reparation from the Brazilian state. We will discuss how, notwithstanding the
      voluntary nature of tests, mediated at all times through the social movement, the
      geneticists take care to follow clear ethical guidelines in the collection and
      stocking of DNA samples as well as in the devolution of test results. The
      subsequent inclusion of anthropologists in the team brings to the fore new
      ethical dilemmas ranging from procedures in field research to the possible
      consequences of research results. 

PMID- 25966989
TI  - Heat fixation inactivates viral and bacterial pathogens and is compatible with
      downstream MALDI mass spectrometry tissue imaging.
AB  - BACKGROUND: Tissue samples should be fixed and permanently stabilized as soon as
      possible ex-vivo to avoid variations in proteomic content. Tissues collected from
      studies involving infectious microorganisms, must face the additional challenge
      of pathogen inactivation before downstream proteomic analysis can be safely
      performed. Heat fixation using the Denator Stabilizor System (Gothenburg, Sweden)
      utilizes conductive heating, under a mild vacuum, to rapidly eliminate enzymatic
      degradation in tissue samples. Although many studies have reported on the ability
      of this method to stop proteolytic degradation and other sample changes
      immediately and permanently, pathogen inactivation has not been studied. RESULTS:
      We examined the ability of the heat fixation workflow to inactivate bacterial and
      viral pathogens and the suitability of this tissue for Matrix Assisted Laser
      Desorption Ionization mass spectrometry imaging (MALDI-MSI). Mice were infected
      with viral or bacterial pathogens representing two strains of Venezuelan Equine
      Encephalitis virus (VEEV) and two strains of Burkholderia. Additionally, a tissue
      mimetic model was employed using Escherichia, Klebsiella and Acinetobacter
      isolates. Infected tissue samples harvested from each animal or mimetic model
      were sectioned in half. One half was heat fixed and the other remained untreated.
      Lysates from each sample were checked for organism viability by performing plaque
      (infectivity) assays or plating on nutrient agar for colony forming unit (CFU)
      calculation. Untreated infected control tissue demonstrated the presence of each
      viable pathogen by positive plaque or colony formation, whereas heat fixation
      resulted in complete inactivation of both the viral and bacterial pathogens.
      MALDI-MSI images produced from heat fixed tissue were reflective of molecular
      distributions within brain, spleen and lung tissue structures. CONCLUSIONS: We
      conclude that heat fixation inactivates viral and bacterial pathogens and is
      compatible with proteomic analysis by MALDI-MSI. This treatment will enable the
      use of infected tissue from studies performed in bio-safety level 3 laboratories
      with VEEV and Burkholderia to be safely used for proteomic, small molecule drug
      detection, and imaging mass spectrometry analysis.

PMID- 25966991
TI  - The need to do better - Are we still letting our patients down and at what cost?
AB  - OBJECTIVE: To survey women's views on HRT and alternative therapies and make
      comparisons with 2007 data. STUDY DESIGN: A questionnaire on a UK patient
      tailored independent clinician-led website with anonymous responses analysed
      using descriptive statistics. MAIN OUTCOME MEASURES: Answers to survey questions
      in 2007 and 2014. RESULTS: A total of 1476 responses from 33 countries were
      obtained. Almost 70% of respondents had used/would consider using HRT. Over the
      last 5 years, 27.7% felt that their views had changed for the better. Most
      obtained information from health professionals or the Internet. About 51.1% felt
      that their family doctor did not recognise the importance of the menopause with
      one-third feeling resistance to being offered HRT. Compared to 2007,
      significantly more women were aware of the different risks associated with
      different types of HRT. More women were able to respond positively to the
      question asking whether or not they felt able to make an informed choice
      regarding HRT/alternative therapies. CONCLUSIONS: There has been negativity and
      confusion regarding HRT management since the beginning of the millennium. Our
      findings suggest that we, as health professionals, continue to let our patients
      down with poor provision of information, inaccurate or wrong information, or
      access to the right care. The cost of this is women living with preventable
      sequelae associated with the menopausal transition with a consequent adverse
      impact on health and the health economy. The importance of the menopause
      consultation as part of a life course approach is highlighted as well as the
      emerging discipline of Health Web Science.

PMID- 25966992
TI  - Tailored anti-TNF therapy during pregnancy in patients with IBD: maternal and
      fetal safety.
AB  - OBJECTIVE: Antitumour necrosis factor (TNF) during pregnancy in patients with IBD
      is related to high fetal anti-TNF levels. We evaluated maternal and child safety
      on discontinuing anti-TNF in the second trimester of pregnancy. DESIGN: Two
      groups of women with IBD were prospectively followed-up during pregnancy: women
      in sustained remission stopped anti-TNF before week 25 (stop group) and the
      remaining group continued anti-TNF beyond week 30 (continue group). Maternal,
      birth and 1-year child outcomes were compared with children of non-IBD women.
      RESULTS: Overall, 106 patients with 83 completed pregnancies were included.
      Relapse rate after week 22 did not differ between the stop (n=51) and continue
      (n=32) groups (5 (9.8%) versus 5 (15.6%), p=0.14). There was no difference in
      allergic reactions (p=1.00) or loss of response (p=1.00) postpartum between the
      two groups. Birth outcomes were comparable. Infants from both groups had lower
      birth weight (p=0.001), shorter gestational term (p=0.0001), were more often
      delivered via caesarean section (p=0.0001) and were less often breastfed
      (p=0.0001) compared with infants from non-IBD controls. Growth, infection rate,
      allergies, eczema and adverse reactions to vaccines were comparable across the
      stop and the continue groups as well as the children of anti-TNF-exposed and non
      IBD women at 1 year. CONCLUSIONS: To limit anti-TNF exposure in utero, anti-TNF
      can be stopped safely in the second trimester in women with IBD in sustained
      remission. In patients not in sustained remission, anti-TNF may be continued
      without clear additional risks to the fetus. We observed excellent 1-year child
      outcomes compared with children from non-IBD controls.

PMID- 25966994
TI  - When antimicrobial peptides hit the wrong target: a novel link between tumour
      macrophages and cancer stem cells.

PMID- 25966993
TI  - PHLDA3 overexpression in hepatocytes by endoplasmic reticulum stress via IRE1
      Xbp1s pathway expedites liver injury.
AB  - OBJECTIVE: Endoplasmic reticulum (ER) stress is involved in liver injury, but
      molecular determinants are largely unknown. This study investigated the role of
      pleckstrin homology-like domain, family A, member-3 (PHLDA3), in hepatocyte death
      caused by ER stress and the regulatory basis. DESIGN: Hepatic PHLDA3 expression
      was assessed in HCV patients with hepatitis and in several animal models with ER
      stress. Immunoblottings, PCR, reporter gene, chromatin immunoprecipitation (ChIP)
      and mutation analyses were done to explore gene regulation. The functional effect
      of PHLDA3 on liver injury was validated using lentiviral delivery of shRNA.
      RESULTS: PHLDA3 was overexpressed in relation to hepatocyte injury in patients
      with acute liver failure or liver cirrhosis or in toxicant-treated mice. In HCV
      patients with liver injury, PHLDA3 was upregulated in parallel with the induction
      of ER stress marker. Treatment of mice with tunicamycin (Tm) (an ER stress
      inducer) increased PHLDA3 expression in the liver. X box-binding protein-1 (Xbp1)
      was newly identified as a transcription factor responsible for PHLDA3 expression.
      Inositol-requiring enzyme 1 (IRE1) (an upstream regulator of Xbp1) was required
      for PHLDA3 induction by Tm, whereas other pathways (c-Jun N-terminal kinase
      (JNK), protein kinase RNA-like endoplasmic reticulum kinase (PERK) and activating
      transcription factor 6 (ATF6)) were not. PHLDA3 overexpression correlated with
      the severity of hepatocyte injury in animal or cell model of ER stress. In p53
      deficient cells, ER stress inducers transactivated PHLDA3 with a decrease in cell
      viability. ER stress-induced hepatocyte death depended on serine/threonine
      protein kinase B (Akt) inhibition by PHLDA3. Lentiviral delivery of PHLDA3 shRNA
      to mice abrogated p-Akt inhibition in the liver by Tm, attenuating hepatocyte
      injury. CONCLUSIONS: ER stress in hepatocytes induces PHLDA3 via IRE1-Xbp1s
      pathway, which facilitates liver injury by inhibiting Akt.

PMID- 25966995
TI  - The composition and differentiation potential of the duodenal intraepithelial
      innate lymphocyte compartment is altered in coeliac disease.
AB  - OBJECTIVE: Coeliac disease (CD), a gluten-induced enteropathy, alters the
      composition and function of duodenal intraepithelial T cells. The intestine also
      harbours four types of CD3-negative intraepithelial lymphocytes (IELs) with
      largely unknown function: CD56(-)CD127(-), CD56(-)CD127(+), CD56(+)CD127(-) and
      CD56(+)CD127(+). Here we aimed to gain insight into the potential function of
      these innate IELs in health and disease. DESIGN: We determined the phenotypes,
      relative abundance and differentiation potential of these innate IEL subsets in
      duodenal biopsies from controls and patients with CD or patients with refractory
      CD type II (RCDII). RESULTS: Hierarchical clustering analysis of the expression
      of 15 natural killer and T cell surface markers showed that innate IELs differed
      markedly from innate peripheral blood lymphocytes and divided innate IEL subsets
      into two main branches: a CD127(-) branch expressing high levels of interleukin
      (IL) 2/15Rbeta but no IL-21R, and a CD127(+) branch with the opposite phenotype.
      While CD was characterised by the contraction of all four innate IEL subsets, a
      selective expansion of CD56(-)CD127(-) and CD56(-)CD127(+) innate IEL was
      detected in RCDII. In vitro, in the presence of IL-15, CD56(-)CD127(-) IEL from
      controls and patients with CD, but not from patients with RCDII, differentiated
      into functional natural killer and T cells, the latter largely dependent on notch
      signalling. Furthermore, compared with non-coeliac controls, CD56(-)CD127(-) IEL
      from patients with CD expressed more intracellular CD3epsilon and CD3gamma and
      gave more pronounced T cell differentiation. CONCLUSIONS: Thus, we demonstrate
      previously unappreciated diversity and plasticity of the innate IEL compartment
      and its loss of differentiation potential in patients with RCDII.

PMID- 25966997
TI  - Differences between glioblastomas and primary central nervous system lymphomas in
      1H-magnetic resonance spectroscopy.
AB  - PURPOSE: The present study aimed to distinguish between glioblastomas and primary
      central nervous system lymphomas (PCNSLs) using (1)H-magnetic resonance
      spectroscopy (MRS), especially glutamate (Glu)/creatine (Cr) and
      Glu/Glu+glutamine (Gln) ratios. MATERIALS AND METHODS: A total of 46 patients (31
      cases diagnosed with glioblastoma, 15 with PCNSL) were examined by in vivo single
      voxel proton (1)H-MRS with a 3-T MR imaging system. Differences in absolute
      concentration of Cr, choline/Cr, lipid (1.3 ppm)/Cr, Glu+Gln/Cr, Glu/Cr, and
      Glu/Glu+Gln ratios among groups were evaluated with Mann-Whitney U tests.
      RESULTS: PCNSLs [3.408 +/- 1.194 (standard deviation)] showed significantly
      higher Glu/Cr ratios as compared to glioblastomas (2.220 +/- 0.942; P = 0.003)
      [Glu/Cr cutoff ratio of 2.509 showed a sensitivity of 88 % (7/8) and a
      specificity of 92 % (22/24)], while glioblastomas (0.539 +/- 0.098) showed
      significantly lower Glu/Glu+Gln ratios as compared to PCNSLs (0.728 +/- 0.147; P
      < 0.001) [Glu/Glu+Gln cutoff ratio of 0.558 showed a sensitivity of 69 % (18/26)
      and a specificity of 100 % (13/13)]. And PCNSLs (1.101 +/- 0.387) showed
      significantly higher Cho/Cr ratios as compared to glioblastomas (0.850 +/- 0.465;
      P = 0.026). CONCLUSION: Glu/Cr, Glu/Glu+Gln, and Cho/Cr ratios may be useful in
      distinguishing between glioblastomas and PCNSLs.

PMID- 25966999
TI  - High-Q and high-sensitivity width-modulated photonic crystal single nanobeam air
      mode cavity for refractive index sensing.
AB  - We propose a novel optical sensor based on a one-dimensional (1D) photonic
      crystal (PhC) single nanobeam air-mode cavity (SNAC). The performance of the
      device is investigated theoretically. By introducing a quadratically modulated
      width tapering structure, a waveguide-coupled 1D-PhC SNAC with a calculated high
      quality factor of 5.16*10(6) and an effective mode volume of
      V(eff)~2.18(lambda/n(si))(3) can be achieved. For the air mode mentioned above,
      the light field can be strongly localized inside the air region (low index) and
      overlaps sufficiently with the analytes. Thus, the suggested PhC SNAC can be used
      for high-sensitivity refractive index sensing with an estimated high sensitivity
      of 537.8 nm/RIU. To the best of our knowledge, this is the first PhC single
      nanobeam geometry that features both high Q-factors and high sensitivity, and is
      potentially an ideal platform for realizing ultracompact lab-on-a-chip
      applications with dense arrays of functionalized spots for multiplexed sensing.

PMID- 25966998
TI  - Tobacco use and associated factors among adults in Ethiopia: further analysis of
      the 2011 Ethiopian Demographic and Health Survey.
AB  - BACKGROUND: Tobacco is one of the leading preventable causes of non-communicable
      diseases. Previous studies gave due emphasis only for cigarette smoking with
      little attention given for other types of tobacco use. This study describes the
      prevalence of all common forms of tobacco use and identify associated factors
      among adults in Ethiopia. METHODS: The study used data from the 2011 Ethiopian
      demographic and health survey. An index was constructed from yes or no responses
      for common types of tobacco use. Bivariate and multivariate logistic regression
      statistical models were employed to determine associated factors with tobacco
      using adjusted odds ratios (AOR) and their 95 % confidence intervals (CI).
      RESULTS: The overall prevalence of tobacco use was 4.1 % [95 % CI: (3.93-4.37)].
      The highest prevalence 16.9 % [95 % CI: (11.02-23.76)] in Gambella and the lowest
      0.8 % [95 % CI: (0.48-1.29)] in Tigray regions were reported. The odds of tobacco
      use in the age group 20-24 and 45-49 years were [AOR = 2.3; 95 % CI: (1.60-3.21)]
      and [AOR = 9.1; 95 % CI: (6.06-13.54)] more likely to use tobacco, respectively,
      as compared to the age group 15-19 years. Traditional religion [AOR = 5.5; 95 %
      CI: (3.96-7.55)], Catholics [AOR = 3.40; 95 % CI: (2.03-5.69)] and Islamic
      followers [AOR = 2.8; 95 % CI: (2.31-3.32)] had higher odds of using tobacco as
      compared to Orthodox religion followers. Adults in the poorest wealth quintile
      were [AOR = 1.4; 95 % CI: (1.05-1.79)] more likely to use tobacco as compared to
      the richest wealth quintile. The odds of tobacco use among males were higher as
      compared to females [AOR = 13.08; 95 % CI: (10.24-16.72)]. Formerly married
      adults were [AOR = 1.71; 95 % CI: (1.20-2.34)] more likely to use tobacco as
      compared to never married. Adults who were professionally working [AOR = 0.49; 95
      % CI: (0.29-0.85)] had less likely to use tobacco as compared to non-working
      adults. However, adults who were working in sales, skilled and unskilled
      occupations had [AOR = 1.6; 95 % CI: (1.18-2.24)], [AOR = 1.7, 95 % CI: (1.21
      2.50)] and [AOR = 3.8 95 % CI: (2.27-6.23)] more likely to use tobacco,
      respectively, as compared to non-working adults. Individuals who had experience
      of child death were [AOR = 1.4; 95 % CI: (1.17-1.63)] more likely to use tobacco
      as compared to their counterparts. CONCLUSION: The overall prevalence of tobacco
      use seems low in Ethiopia. However, a significant regional variation of tobacco
      use was observed. A tailored public health interventions targeting regions with
      high prevalence of tobacco use is recommended.

PMID- 25967000
TI  - Stable single-polarization single-longitudinal-mode linear cavity erbium-doped
      fiber laser based on structured chirped fiber Bragg grating.
AB  - A novel linear cavity erbium-doped fiber (EDF) laser based on a structured
      chirped fiber Bragg grating (CFBG) filter is proposed for stable single
      polarization (SP) single-longitudinal-mode (SLM) operation. For the first time,
      to the best of our knowledge, a structured CFBG filter with an ultranarrow
      transmission band which is generated by tapering directly on CFBG is used to
      select the laser longitudinal mode. The SLM operation is obtained by using the
      structured CFBG together with an unpumped EDF acting as a saturable absorber. The
      fluctuations of the laser peak power and center wavelength are less than 0.07 dB
      and 1 pm in 1 h, respectively. The stable SP operation is achieved by using the
      inline broadband polarizer. The measured 20 dB laser linewidth is about 27.7 kHz,
      which indicates the laser linewidth is approximately 1.39 kHz FWHM. 

PMID- 25966996
TI  - Lineage-specific gene radiations underlie the evolution of novel betalain
      pigmentation in Caryophyllales.
AB  - Betalain pigments are unique to the Caryophyllales and structurally and
      biosynthetically distinct from anthocyanins. Two key enzymes within the betalain
      synthesis pathway have been identified: 4,5-dioxygenase (DODA) that catalyzes the
      formation of betalamic acid and CYP76AD1, a cytochrome P450 gene that catalyzes
      the formation of cyclo-DOPA. We performed phylogenetic analyses to reveal the
      evolutionary history of the DODA and CYP76AD1 lineages and in the context of an
      ancestral reconstruction of pigment states we explored the evolution of these
      genes in relation to the complex evolution of pigments in Caryophylalles.
      Duplications within the CYP76AD1 and DODA lineages arose just before the origin
      of betalain pigmentation in the core Caryophyllales. The duplications gave rise
      to DODA-alpha and CYP76AD1-alpha isoforms that appear specific to betalain
      synthesis. Both betalain-specific isoforms were then lost or downregulated in the
      anthocyanic Molluginaceae and Caryophyllaceae. Our findings suggest a single
      origin of the betalain synthesis pathway, with neofunctionalization following
      gene duplications in the CYP76AD1 and DODA lineages. Loss of DODA-alpha and
      CYP76AD1-alpha in anthocyanic taxa suggests that betalain pigmentation has been
      lost twice in Caryophyllales, and exclusion of betalain pigments from anthocyanic
      taxa is mediated through gene loss or downregulation. [Correction added after
      online publication 13 May 2015: in the last two paragraphs of the Summary the
      gene name CYP761A was changed to CYP76AD1.]. 

PMID- 25967001
TI  - One-way visibility using two parallel aerosol clouds.
AB  - In this article, we experimentally and theoretically test the range of
      applicability of a patent that predicts one-way visibility through two successive
      parallel aerosol clouds, one scattering dominant and the other absorption
      dominant. A laboratory environment experiment has been designed to determine the
      ranges of transmissivity and contrast enhancement that might be of interest for
      military applications. In this study we show that transmissivities in the several
      percent range and lower are essential for any reasonable contrast enhancement
      between the two sides of the clouds. 

PMID- 25967002
TI  - Effect of the optical system on the Doppler spectrum in laser-feedback
      interferometry.
AB  - We present a comprehensive analysis of factors influencing the morphology of the
      Doppler spectrum obtained from a laser-feedback interferometer. We explore the
      effect of optical system parameters on three spectral characteristics: central
      Doppler frequency, broadening, and signal-to-noise ratio. We perform four sets of
      experiments and replicate the results using a Monte Carlo simulation calibrated
      to the backscattering profile of the target. We classify the optical system
      parameters as having a strong or weak influence on the Doppler spectrum. The
      calibrated Monte Carlo approach accurately reproduces experimental results, and
      allows one to investigate the detailed contribution of system parameters to the
      Doppler spectrum, which are difficult to isolate in experiment. 

PMID- 25967003
TI  - Analysis of experimental depolarizing Mueller matrices through a hybrid
      decomposition.
AB  - We propose a new decomposition for depolarizing Mueller matrices. This
      decomposition, which consists of a product of four basic optical devices (two
      diattenuators, a retarder, and a depolarizer) is derived from a previous one
      known as "symmetric decomposition" [J. Opt. Soc. Am. A26, 1109
      (2009)10.1364/JOSAA.26.001109JOAOD61084-7529] and makes it easier to interpret
      polarization properties of Mueller matrices and improves estimation of the
      extracted parameters. Its application is illustrated by several theoretical and
      experimental examples. 

PMID- 25967004
TI  - Support vector machine firefly algorithm based optimization of lens system.
AB  - Lens system design is an important factor in image quality. The main aspect of
      the lens system design methodology is the optimization procedure. Since
      optimization is a complex, nonlinear task, soft computing optimization algorithms
      can be used. There are many tools that can be employed to measure optical
      performance, but the spot diagram is the most useful. The spot diagram gives an
      indication of the image of a point object. In this paper, the spot size radius is
      considered an optimization criterion. Intelligent soft computing scheme support
      vector machines (SVMs) coupled with the firefly algorithm (FFA) are implemented.
      The performance of the proposed estimators is confirmed with the simulation
      results. The result of the proposed SVM-FFA model has been compared with support
      vector regression (SVR), artificial neural networks, and generic programming
      methods. The results show that the SVM-FFA model performs more accurately than
      the other methodologies. Therefore, SVM-FFA can be used as an efficient soft
      computing technique in the optimization of lens system designs. 

PMID- 25967005
TI  - High-gain 1.3  MUm GaInNAs semiconductor optical amplifier with enhanced
      temperature stability for all-optical signal processing at 10  Gb/s.
AB  - We report on the complete experimental evaluation of a GaInNAs/GaAs (dilute
      nitride) semiconductor optical amplifier that operates at 1.3 MUm and exhibits 28
      dB gain and a gain recovery time of 100 ps. Successful wavelength conversion
      operation is demonstrated using pseudorandom bit sequence 2<sup>7</sup>-1 non
      return-to-zero bit streams at 5 and 10  Gb/s, yielding error-free performance and
      showing feasibility for implementation in various signal processing
      functionalities. The operational credentials of the device are analyzed in
      various operational regimes, while its nonlinear performance is examined in terms
      of four-wave mixing. Moreover, characterization results reveal enhanced
      temperature stability with almost no gain variation around the 1320 nm region for
      a temperature range from 20 degrees C to 50 degrees C. The operational
      characteristics of the device, along with the cost and energy benefits of dilute
      nitride technology, make it very attractive for application in optical access
      networks and dense photonic integrated circuits. 

PMID- 25967006
TI  - Polarization-controlled images based on double-exposure polarization holography
      in an azobenzene liquid-crystalline polymer.
AB  - Polarization-controlled optical image operations were demonstrated based on the
      double-exposure polarization holographic method. Two images were stored in the
      same volume of an azobenzene liquid-crystalline polymer by recording superimposed
      holograms, a pair of polarization gratings with one spatial frequency, using two
      orthogonal circularly polarized 532 nm beams and were reconstructed with a 650 nm
      laser. The recorded polarization holographic gratings were investigated to show
      distinctive polarization selectivity, high diffraction efficiency, and good
      stability. The brightness and the polarization of the diffracted images were
      found to be dependent on the polarization of the readout beam, and two images
      could be reconstructed individually or simultaneously. 

PMID- 25967007
TI  - Design of a high-numerical-aperture digital micromirror device camera with high
      dynamic range.
AB  - A high-NA imaging system with high dynamic range is presented based on a digital
      micromirror device (DMD). The DMD camera consists of an objective imaging system
      and a relay imaging system, connected by a DMD chip. With the introduction of a
      total internal reflection prism system, the objective imaging system is designed
      with a working F/# of 1.97, breaking through the F/2.45 limitation of
      conventional DMD projection lenses. As for the relay imaging system, an off-axis
      design that could correct off-axis aberrations of the tilt relay imaging system
      is developed. This structure has the advantage of increasing the NA of the
      imaging system while maintaining a compact size. Investigation revealed that the
      dynamic range of a DMD camera could be greatly increased, by 2.41 times. We built
      one prototype DMD camera with a working F/# of 1.23, and the field experiments
      proved the validity and reliability our work.

PMID- 25967008
TI  - Initial conditions for dark soliton generation in normal-dispersion fiber lasers.
AB  - We report results of numerical simulations on the various initial conditions for
      dark soliton generation in an all-normal-dispersion fiber laser. All the dark
      solitons generated are odd dark solitons. Differently from the dark soliton
      generation in fibers, where an arbitrary dip could evolve into a dark soliton, it
      is found that the dark soliton can originate only from an initial dip with a
      certain parameter requirement. A bright pulse with either a hyperbolic secant
      square, Gaussian, or Lorentz profile can be developed into a dark soliton,
      provided that the parameters of the initial bright pulse are selected. Dark
      solitons can be generated in fiber lasers only if there is a phase jump, and this
      phase jump can be maintained and evolve to pi during the pulse evolution. 

PMID- 25967009
TI  - Spectral measurement of birefringence using particle swarm optimization analysis.
AB  - Measurement of birefringence is useful for the examination of technical and
      biological objects. One of the main problems, however, is that the polarization
      state of light in birefringent media changes periodically. Without knowledge of
      the period number, the birefringence of a given medium cannot be reliably
      determined. We propose to analyze the spectrum of light in order to determine the
      birefringence. We use a particle swarm optimization algorithm for an automatic
      processing spectra of light transmitted through birefringent material for two
      orthogonal states of polarization. We have tested the described algorithm on a
      liquid crystal cell with varying effective birefringence. The proposed method can
      be used for the measurement of uniaxial positive birefringence without knowing
      the number of retardation periods or an approximate value of the measurement
      result. This fact makes the proposed method useful for automatic measurements,
      when hundreds or thousands of spectra need to be analyzed. 

PMID- 25967010
TI  - Comprehensive model for predicting perceptual image quality of smart mobile
      devices.
AB  - An image quality model for smart mobile devices was proposed based on visual
      assessments of several image quality attributes. A series of psychophysical
      experiments were carried out on two kinds of smart mobile devices, i.e., smart
      phones and tablet computers, in which naturalness, colorfulness, brightness,
      contrast, sharpness, clearness, and overall image quality were visually evaluated
      under three lighting environments via categorical judgment method for various
      application types of test images. On the basis of Pearson correlation
      coefficients and factor analysis, the overall image quality could first be
      predicted by its two constituent attributes with multiple linear regression
      functions for different types of images, respectively, and then the mathematical
      expressions were built to link the constituent image quality attributes with the
      physical parameters of smart mobile devices and image appearance factors. The
      procedure and algorithms were applicable to various smart mobile devices,
      different lighting conditions, and multiple types of images, and performance was
      verified by the visual data. 

PMID- 25967011
TI  - Temperature dependence of an optical narrow-bandpass filter at 1.5  MUm.
AB  - For superconducting nanowire single-photon detectors, we designed and fabricated
      an on-chip narrow-bandpass filter at the central wavelength of 1.5 MUm to reduce
      the influence of blackbody radiation from the fiber. The bandpass filter was
      prepared on a thermally oxidized Si substrate, and it provided a peak
      transmittance of 88% at the central passband wavelength and 30 dB suppression at
      the stop bands. We investigate the temperature dependence of the filter from room
      temperature to 2.9 K. The central wavelength of the passband blue-shifted from
      1545+/-2  nm (295 K) to 1526+/-2  nm (2.9 K). This effect is explained by the
      different indices of refraction of Si at different temperatures. 

PMID- 25967013
TI  - Reduction of backscattering noise in a resonator integrated optic gyro by double
      triangular phase modulation.
AB  - A high carrier suppression level is required to reduce the backscattering noise
      of a resonator integrated optic gyro (RIOG). This paper proposes a double
      triangular phase modulation (DTPM) technology for backscattering noise reduction.
      The principle of the DTPM is described and the carrier suppression of the DTPM is
      theoretically analyzed and simulated. Based on the numerical simulations, the
      modulation parameters of the DTPM are optimized. Compared with single triangular
      phase modulation technology, the DTPM can not only achieve higher carrier
      suppression but also relax the requirements of modulation amplitude accuracy and
      temperature stability. The advantage of the DTPM for carrier suppression is
      validated by experiments, demonstrating that the DTPM is helpful in
      backscattering noise reduction. As a result, the experimental setup of the RIOG
      based on the DTPM is established: a bias stability of 0.22  deg/s (10 s
      integrated time) is achieved for 1 h. To our knowledge, this is the best long
      term bias stability of an RIOG reported to date. 

PMID- 25967012
TI  - Analysis of multimode fiber bundles for endoscopic spectral-domain optical
      coherence tomography.
AB  - A theoretical analysis of the use of a fiber bundle in spectral-domain optical
      coherence tomography (OCT) systems is presented. The fiber bundle enables a
      flexible endoscopic design and provides fast, parallelized acquisition of the OCT
      data. However, the multimode characteristic of the fibers in the fiber bundle
      affects the depth sensitivity of the imaging system. A description of light
      interference in a multimode fiber is presented along with numerical simulations
      and experimental studies to illustrate the theoretical analysis. 

PMID- 25967014
TI  - Discrimination of healthy and carious teeth using laser-induced breakdown
      spectroscopy and partial least square discriminant analysis.
AB  - In the laser drilling of teeth, a microplasma is generated which may be utilized
      for elemental analysis of ablated tissue via a laser-induced breakdown
      spectroscopy (LIBS) technique. In this study, LIBS is used to investigate the
      possibility of discrimination of healthy and carious tooth tissues. This
      possibility is examined using multivariate statistical analysis called partial
      least square discriminant analysis (PLS-DA) based on atomic and ionic emission
      lines of teeth LIBS spectra belonging to P, Ca, Mg, Zn, K, Sr, C, Na, H, and O
      elements. Results show an excellent discrimination and prediction of unknown
      tooth tissues. It is shown that using the PLS-DA method, the spectroscopic
      analysis of plasma emission during the laser drilling, would be a promising
      technique for caries detection. 

PMID- 25967015
TI  - Determination of two-photon absorption cross sections of photosensitizers and its
      implications for two-photon polymerization.
AB  - We report two-photon absorption cross sections and two-photon excited
      fluorescence of the photosensitizer 4,4'-Bis(diethylamino)benzophenon and
      thioxanthone using a femtosecond laser delivering pulses of wavelength 800 nm and
      150 fs duration at rates of 1 kHz. Values for the two-photon absorption cross
      section are derived by comparing the fluorescence signals excited by wavelengths
      of 800 and 400 nm using a second-harmonic generator. Fluorophore fluorescence
      intensities dependence with quadratic illumination laser power showed no
      significant deviation from the two-photon absorption process. Implications of
      these cross-section measurements for two-photon polymerization are discussed.

PMID- 25967016
TI  - Stochastic digital holography for visualizing inside strongly refracting
      transparent objects.
AB  - This paper presents a digital holographic method to visualize and measure
      refractive index variations, convection currents, or thermal gradients, occurring
      inside a transparent and refracting object. The proof of principle is provided
      through the visualization of refractive index variation inside a lighting bulb.
      Comparison with transmission and reflection holography is also provided. A very
      good agreement is obtained, thus validating the proposed approach. 

PMID- 25967017
TI  - Recording spatially incoherent Fourier hologram using dual channel rotational
      shearing interferometer.
AB  - The method to record an incoherent Fourier hologram is proposed. The interference
      patterns in the dual channel rotational shearing interferometer are obtained as
      the figure of the cosine and the sine transformation in the vertical and the
      horizontal polarization, respectively. The proposed optical system is simple
      without spatial light modulators or mechanical phase shifting devices. The
      experiment, in which the letter "A" displayed on a liquid crystal display with a
      blue LED backlight was used as an object, confirms the proposed method to obtain
      an incoherent Fourier hologram. 

PMID- 25967018
TI  - Characterization of atomization and breakup of acoustically levitated drops with
      digital holography.
AB  - A digital holographic particle tracking velocimetry system is applied to
      quantitatively study the drop atomization induced by capillary waves, and the
      breakup caused by increased sound pressure levels. A wavelet-based algorithm is
      used for particle detection and autofocusing with a wide size range of 20 MUm-2
      mm. To eliminate the influence of large particles on small particles, a two-step
      detection method is adopted. Large drops are first characterized and simulated by
      a diffraction-based model. Then the contributions of the drops are subtracted
      from the original hologram followed by the detection of small droplets. Finally,
      the velocity and size distribution of the secondary droplets are obtained from
      the experimental holograms. The results demonstrate the validity of the digital
      in-line holographic technique for the atomization and breakup study of
      acoustically levitated drops. 

PMID- 25967019
TI  - Common-path on-axis Fresnel holography based on a pinhole array plate.
AB  - A common-path and on-axis configuration for improving the resolution power of a
      lensless Fresnel holographic imaging system is proposed. In this configuration, a
      pinhole array plate (PAP) is inserted between the object and the recording plane.
      We demonstrated that the complex amplitude of the object wave can be directly
      extracted from a single Fresnel hologram of the object wave sampled by the PAP,
      and the numerical aperture of the effective imaging system can be increased
      because of the diffraction effect of the pinhole array. It may provide one
      approach for improving the capabilities of digital holography available for a
      wide range of wavelengths from far-infrared to x-ray and electron beams. 

PMID- 25967020
TI  - Optical frequency comb profilometry using a single-pixel camera composed of
      digital micromirror devices.
AB  - We demonstrate an optical frequency comb profilometer with a single-pixel camera
      to measure the position and profile of an object's surface that exceeds far
      beyond light wavelength without 2pi phase ambiguity. The present configuration of
      the single-pixel camera can perform the profilometry with an axial resolution of
      3.4 MUm at 1 GHz operation corresponding to a wavelength of 30 cm. Therefore, the
      axial dynamic range was increased to 0.87*10<sup>5</sup>. It was found from the
      experiments and computer simulations that the improvement was derived from higher
      modulation contrast of digital micromirror devices. The frame rate was also
      increased to 20 Hz. 

PMID- 25967021
TI  - Three-dimensional image transmission and reconstruction for multisensor imaging
      system using interleaver division multiple access.
AB  - In this paper, we present an optical image transmission and reconstruction system
      of 3D objects using a multisensor imaging system and interleaver division
      multiple access (IDMA) channel. When the 3D image data from the multisensor
      imaging system are transmitted over a wireless channel, loss or distortion of
      original data may occur by wireless channel environment, such as multiple access
      interference and channel noise. To solve this problem, an optical 3D image
      reconstruction scheme and IDMA technique can be used. Reconstructed 3D image data
      at the receiver is clear enough to distinguish the depth of 3D objects. To prove
      our proposed scheme, we carry out an optical experiment for sensing 3D
      information and simulation for data transmission of a multisensor imaging system
      via IDMA with channel noise. 

PMID- 25967022
TI  - Resolution enhancement of spectrum normalization in synthetic aperture digital
      holographic microscopy.
AB  - This study describes the overlapping of spatial frequency bands for synthetic
      aperture in digital holography using spectrum normalization to effectively
      enhance the spatial resolutions of image reconstruction. Synthesized spectrum
      swelling induced by excessive frequency overlaps can be normalized through the
      inverse apodization of an adjustable window function, which is similar to the
      effects of suppressing low-frequency expansion and strengthening high-frequency
      components of the reconstructed images. The results indicated that using the
      normalized spectrum synthesis that requires only a few frequency bands
      effectively enhances the spatial resolution and phase sensitivity of
      reconstructed images in digital holographic microscopy. 

PMID- 25967023
TI  - Spatial coherence analysis for optical scanning holography.
AB  - In optical scanning holography (OSH), the system can be operated in coherent mode
      by using a pinhole detector, or in incoherent mode by using a spatially
      integrating detector. In the coherent mode, the three-dimensional (3D) amplitude
      transparency of an object is recorded and thus the phase of the object can be
      retrieved. On the other hand, it is the 3D intensity transparency of the object
      recorded in the incoherent mode and thus the speckle can be suppressed. OSH in
      both coherence modes has been well investigated. However, there is no discussion
      on the case between the coherent mode and incoherent mode, namely, the partial
      coherent mode. In this paper, we derived for the first time, to the best of our
      knowledge, the formula of OSH in various modes of coherence. We found the
      detector in OSH plays the role of a kind of filter for the field. The retrieved
      amplitude transparency of the object is thus nonlinearly processed by the mask
      function of the detector. Consequently, the reconstructed image cannot benefit
      from the implementation of the partial-coherent mode. On the contrary,
      significant artifacts usually appear among the reconstructed image and thus the
      image quality degrades. 

PMID- 25967024
TI  - Region-referenced phase unwrapping architecture for digital holographic
      microscopy.
AB  - This work presents a novel hardware phase-unwrapping architecture for digital
      holographic microscopy. The architecture is based on an iterative region
      referenced algorithm because of its simplicity and effectiveness for phase
      unwrapping. The architecture therefore consumes fewer hardware resources for very
      large-scale integration implementation. In addition, a novel data reuse scheme is
      adopted for reducing the memory bandwidth required by the architecture. The
      architecture can then have fast computation speed for the iterative operations.
      The architecture has been implemented by field programmable gate array. It acts
      as a hardware accelerator in an embedded system developed by a network-on-chip
      platform for performance measurement. The superiorities of the proposed
      architecture have been confirmed by the experiments. 

PMID- 25967025
TI  - Fast calculation method of a CGH for a patch model using a point-based method.
AB  - Holography is three-dimensional display technology. Computer-generated holograms
      (CGHs) are created by simulating light propagation on a computer, and they are
      able to display a virtual object. There are mainly two types of calculation
      methods of CGHs, a point-based method and the fast Fourier-transform (FFT)-based
      method. The FFT-based method is based on a patch model, and it is suited to
      accelerating the calculations as it calculates the light propagation across a
      patch as a whole. The calculations with the point-based method are characterized
      by a high degree of parallelism, and it is suited to accelerating graphics
      processing units (GPUs). The point-based method is not suitable for calculation
      with the patch model. This paper proposes a fast calculation algorithm for a
      patch model with the point-based method. The proposed method calculates the line
      on a patch as a whole regardless of the number of points on the line. When the
      proposed method is implemented on a GPU, the calculation time of the proposed
      method is shorter than with the point-based method. 

PMID- 25967026
TI  - Three-dimensional information encryption and anticounterfeiting using digital
      holography.
AB  - In this work, arbitrary micro phase-step digital holography with optical
      interferometry and digital image processing is utilized to obtain information
      about an image of a three-dimensional object and encrypting keys. Then, a
      computer-generated hologram is used for the purpose of holographic encryption.
      All information about the keys is required to perform the decryption, comprising
      the amplitude and phase distribution of the encrypting key, the distance of image
      reconstruction, zero-order term elimination, and twin-image term suppression. In
      addition to using identifiable information on different image planes and linear
      superposition processing hidden within the encrypted information, not only can we
      convey an important message, but we can also achieve anticounterfeiting. This
      approach retains the strictness of traditional holographic encryption and the
      convenience of digital holographic processing without image distortion.
      Therefore, this method provides better solutions to earlier methods for the
      security of the transmission of holographic information. 

PMID- 25967027
TI  - Digital holography of intracellular dynamics to probe tissue physiology.
AB  - Digital holography provides improved capabilities for imaging through dense
      tissue. Using a short-coherence source, the digital hologram recorded from
      backscattered light performs laser ranging that maintains fidelity of information
      acquired from depths much greater than possible by traditional imaging
      techniques. Biodynamic imaging (BDI) is a developing technology for live-tissue
      imaging of up to a millimeter in depth that uses the hologram intensity
      fluctuations as label-free image contrast and can study tissue behavior in native
      microenvironments. In this paper BDI is used to investigate the change in
      adhesion-dependent tissue response in 3D cultures. The results show that
      increasing density of cellular adhesions slows motion inside tissue and alters
      the response to cytoskeletal drugs. A clear signature of membrane fluctuations
      was observed in mid-frequencies (0.1-1 Hz) and was enhanced by the application of
      cytochalasin-D that degrades the actin cortex inside the cell membrane. This
      enhancement feature is only observed in tissues that have formed adhesions,
      because cell pellets initially do not show this signature, but develop this
      signature only after incubation enables adhesions to form. 

PMID- 25967028
TI  - Real-time, high-accuracy 3D imaging and shape measurement.
AB  - In spite of the recent advances in 3D shape measurement and geometry
      reconstruction, simultaneously achieving fast-speed and high-accuracy performance
      remains a big challenge in practice. In this paper, a 3D imaging and shape
      measurement system is presented to tackle such a challenge. The fringe-projection
      profilometry-based system employs a number of advanced approaches, such as:
      composition of phase-shifted fringe patterns, externally triggered
      synchronization of system components, generalized system setup, ultrafast phase
      unwrapping algorithm, flexible system calibration method, robust gamma correction
      scheme, multithread computation and processing, and graphics-processing-unit
      based image display. Experiments have shown that the proposed system can acquire
      and display high-quality 3D reconstructed images and/or video stream at a speed
      of 45 frames per second with relative accuracy of 0.04% or at a reduced speed of
      22.5 frames per second with enhanced accuracy of 0.01%. The 3D imaging and shape
      measurement system shows great promise of satisfying the ever-increasing demands
      of scientific and engineering applications. 

PMID- 25967029
TI  - Adaptive nonseparable vector lifting scheme for digital holographic data
      compression.
AB  - Holographic data play a crucial role in recent three-dimensional imaging as well
      as microscopic applications. As a result, huge amounts of storage capacity will
      be involved for this kind of data. Therefore, it becomes necessary to develop
      efficient hologram compression schemes for storage and transmission purposes. In
      this paper, we focus on the shifted distance information, obtained by the phase
      shifting algorithm, where two sets of difference data need to be encoded. More
      precisely, a nonseparable vector lifting scheme is investigated in order to
      exploit the two-dimensional characteristics of the holographic contents.
      Simulations performed on different digital holograms have shown the effectiveness
      of the proposed method in terms of bitrate saving and quality of object
      reconstruction. 

PMID- 25967030
TI  - Feature issue of digital holography and 3D imaging (DH): introduction.
AB  - The OSA Topical Meeting "Digital Holography and 3D Imaging (DH)" was held in
      Seattle, Washington, 13-17 July 2014. Feature issues based on the DH meeting
      series have been released by Applied Optics (AO) since 2007. In this year (2014),
      Optics Express (OE) and AO jointly decided to have one such feature issue in each
      journal. The feature issue includes 27 papers and covers a large range of topics,
      reflecting the rapidly expanding techniques and applications of digital
      holography and 3D imaging. The DH meeting will continue in the future, as
      expected, and the next meeting is scheduled to be held on 24-28 May 2015, at
      Shanghai Institute of Optics and Fine Mechanics, Shanghai, China. 

PMID- 25967031
TI  - Desulfurization of immobilized sulfur-oxidizing bacteria, Thialkalivibrio
      versutus, by magnetic nanaoparticles under haloalkaliphilic conditions.
AB  - OBJECTIVES: As a haloalkaliphilic, sulfur-oxidizing bacteria, Thialkalivibrio
      versutus D301 can remove sulfide, thiosulfate and polysulfide in wastewater, we
      investigated how it might be reused when mixed with high concentrations of
      elemental sulfur. RESULTS: A process is described to immobilize T. versutus cells
      by using superparamagnetic Fe3O4 nanoparticles (NPs) under haloalkaliphilic
      conditions (i.e. pH 9.5, 0.5 M Na(+)). The saturation magnetization value
      (deltas) of immobilized cells was 55.1 emu/g. The Fe3O4 NPs-coated cells had the
      similar sulfur oxidization activity to that of free cells, and they could be
      reused six batch cycles. Analysis of hydraulic diameters showed that bacterial
      cells were immobilized by Fe3O4 NPs due to the nano-size effects. CONCLUSIONS:
      Magnetic immobilization is a convenient technique for cell immobilization under
      haloalkaliphilic conditions and is a promising technology for large scale
      application.

PMID- 25967032
TI  - Potential protection of taurine on antioxidant system and ATPase in brain and
      blood of rats exposed to aluminum.
AB  - OBJECTIVES: Taurine (Tau) is used in clinical treatments but its protection of
      brains against aluminum-induced oxidative damage has been explored for the first
      time. The positive effect of Tau was studied on the activities of antioxidant
      enzymes and ATPase. RESULTS: Aluminum (Al) intake caused significant increasement
      of malondialdehyde (MDA) but reduction of the activities of superoxide dismutase,
      glutathione peroxidase (GSH-Px), Na(+)K(+)-ATPase and Mg(2+)-ATPase in brain
      compared to control group (P < 0.05). Tau administration, however, significantly
      reduced the MDA content, and increased the activities of aforementioned enzymes
      (P < 0.05). The MDA content was higher and the activities of GSH-Px, Ca(2+)
      ATPase and Mg(2+)-ATPase lower in the blood of the Al-treated group' (P < 0.05),
      while Tau markedly decreased MDA content and improved the activities of GSH-Px
      and Ca(2+)-ATPase (P < 0.05). CONCLUSIONS: Tau may play a crucial role in the
      protection of antioxidant system and ATPase against Al-induced toxicity in brain
      and blood of rats.

PMID- 25967033
TI  - Small intestinal injury in mice infected with respiratory influenza A virus:
      evidence for virus induced gastroenteritis.
AB  - OBJECTIVES: Influenza in humans is often accompanied by gastroenteritis-like
      symptoms such as diarrhea and abdominal pain nausea, but the underlying mechanism
      remains unclear. RESULTS: Mice infected with three subtypes of respiratory
      influenza A virus (IAV), particularly H5N1 and H7N2, developed intestinal injury.
      The avian H5N1 and H7N2 IAV were detected in the small intestine, whereas the
      human H1N1 was not detected. Section staining with the sialic acid (SA) receptor
      demonstrated that the small intestine mainly expressed SA alpha2, 3 Gal instead
      of SA alpha2, 6 Gal which preferentially binds to avian IAV. The number of goblet
      and sIgA cells in the small intestine increased, whereas CD4(+) and CD8(+) T
      cells decreased in all infected mice except for CD8(+) T cells increased in H7N2
      infected mice. CONCLUSIONS: Respiratory IAV infection, particularly infected by
      avian IAV, can cause small intestine structural damage and modify the local
      immune response, thereby resulting in gastroenteritis-like symptoms.

PMID- 25967035
TI  - Compressive mechanical stress may activate IKK-NF-kappaB through proinflammatory
      cytokines in MC3T3-E1 cells.
AB  - OBJECTIVE: To determine whether IKK-NF-kappaB is activated either directly by
      compressive mechanical stress or by proinflammatory cytokines produced by MC3T3
      E1 cells under compressive stress loading. RESULTS: MC3T3-E1 cells subjected to
      cyclic uniaxial compressive stress showed increased expression of proinflammatory
      cytokines and activation of the IKK-NF-kappaB signaling pathway with nuclear
      translocation of p65. Following treatment with antibodies to neutralize the
      action of the proinflammatory cytokines, IL-1beta and IL-6, the activation of IKK
      NF-kappaB signaling was notably inhibited in MC3T3-E1 cells subjected to force
      loading. CONCLUSION: IKK-NF-kappaB signaling in MC3T3-E1 cells may be activated
      by proinflammatory cytokines that are produced as a consequence of mechanical
      stress loading and not by direct compressive mechanical stress.

PMID- 25967034
TI  - High-level expression and characterization of a thermophilic beta-mannanase from
      Aspergillus niger in Pichia pastoris.
AB  - OBJECTIVES: A novel, high-level expression, thermostable mannan endo-1,4-beta
      mannosidase is urgently needed for industrial applications. RESULTS: The mannan
      endo-1,4-beta-mannosidase gene (MAN) from Aspergillus niger CBS 513.88 was
      optimized based on the codon usage bias in Pichia pastoris and synthesized by
      overlapping PCR to produce MAN-P. It was expressed in P. pastoris GS115 from a
      constitutive expression vector pHBM-905 M. MAN-P reached 594 mg/l in shake-flasks
      after 192 h induction. On production in a 5 l fermenter, the yield of MAN-P
      reached ~3.5 mg/ml and the enzyme activity was 1612 U/ml. The enzyme exhibited a
      maximum activity of 3049 U/ml at 80  degrees C and retained 60% enzyme activity
      at 80  degrees C for 2 h. The pH optimum was 4.5 and the enzyme was stable over
      the pH range 1.5-11. CONCLUSION: The thermostability of MAN-P is higher than
      other known fungal mannanases and the expression and thermophilic properties make
      MAN-P useful for industrial applications.

PMID- 25967036
TI  - Transcriptomic variation between different Chinese hamster ovary cell lines.
AB  - OBJECTIVES: To identify transcription markers that uniquely determine specific
      Chinese hamster ovary (CHO) cell lines and can be used for the identification of
      cell lines in the process of biopharmaceutical cell-line development. RESULTS:
      Five CHO cell lines with different origins were extensively characterised at the
      transcriptomic level and the results were compared to their karyotype
      characterisation. The analysed cell lines differ in their karyotype but, due to
      the genome instability observed during parental and recombinant cell-line
      establishment, karyotyping is not the preferred method for accurate
      identification of the various CHO cell lines. Marker genes unique to a specific
      cell line were identified by microarrays, and their expression was validated by
      reverse-transcription quantitative real-time PCR. The analysed cell lines can be
      differentiated by the presence/absence of detectable marker gene expression.
      Additionally, the similarity of the transcriptional profiles is dependent on cell
      line history but independent of the manipulation steps involved in the
      recombinant cell-line development process. CONCLUSIONS: Certain transcripts can
      be used as markers for the identification of a CHO cell line undergoing
      recombinant development and thus represent a powerful tool for ensuring the
      maintenance of high quality standards.

PMID- 25967037
TI  - Engineering of a hybrid route to enhance shikimic acid production in
      Corynebacterium glutamicum.
AB  - OBJECTIVES: To exploit the archaeal shikimic acid (SA) synthesis pathway
      toenhance SA production in Corynebacterium glutamicum. RESULTS: Genetic cassettes
      were constructed that encoded a hybrid route for SA synthesis, which were
      composed of the archaeal 6-deoxy-5-ketofructose 1-phosphate pathway and the
      bacterial SA pathway. Corynebacterium glutamicum strains that expressed the
      hybrid route increased SA production by 57%. A recombinant strain of C.
      glutamicum that simultaneously overexpressed the hybrid route and its native SA
      pathway produced 4.7 gSA/l, while C. glutamicum with only the native SA pathway
      produced 3.7 gSA/l. CONCLUSIONS: A new hybrid route for SA production was
      successfully constructed, that effectively increased SA production in C.
      glutamicum.

PMID- 25967038
TI  - Mechanical, thermal and bio-compatibility studies of PAEK-hydroxyapatite
      nanocomposites.
AB  - In this study high performance bone analogue has been developed using poly(aryl
      ether) ketone, poly(dimethyl siloxane) and reinforced with nanohydroxyapatite as
      biocompatible filler. Compressive, tensile and flexural properties have shown
      sustained improvement up to 7% of nanohydroxyapatite loading. The mechanical
      properties were further analyzed using micromechanical theories for good
      interfacial adhesion between matrix and filler. The composites are cytocompatible
      and revealed multiple layers of apatite formation in simulated body fluid. The
      thickness of apatite layer increased with increase in nanohydroxyapatite loading
      in the composite. Poly(dimethyl siloxane) has been grafted with phosphate group
      to enhance compatibility with nanohydroxyapatite. Nanohydroxyapatite has been
      treated with silane to enhance compatibility and facilitate dispersion in the
      matrix as observed through transmission electron microscopy, scanning electron
      microscopy and X-Ray diffraction studies. 

PMID- 25967039
TI  - Effect of aqueous solution and load on the formation of DLC transfer layer
      against Co-Cr-Mo for joint prosthesis.
AB  - Diamond-like carbon (DLC) coating exhibits excellent mechanical properties such
      as high hardness, low friction and wear, which offer a promising solution for the
      metal-on-metal hip joint implants. In the study, the hydrogen-free DLC coating
      with the element Cr as the interlay addition was deposited on the surface of the
      Co-Cr-Mo alloy by a unbalanced magnetron sputtering method. The coating thickness
      was controlled as 2 um. Nano-indentation test indicated the hardness was about 13
      GPa. DLC coated Co-Cr-Mo alloy disc against un-coated Co-Cr-Mo alloy pin
      (spherical end SR9.5) comprised the friction pairs in the pin-on-disc tribotest
      under bovine serum albumin solution (BSA) and physiological saline(PS).The
      tribological behavior under different BSA concetrations(2-20 mg/ml), and applied
      load (2-15N) was investigated.DLC transfer layer did not form under BSA solution,
      even though different BSA concetration and applied load changed. The coefficient
      of friction(COF) under 6 mg/ml BSA at 10 N was the lowest as 0.10. A higher COF
      of 0.13 was obtained under 20 mg/ml BSA. The boundary absorption layer of protein
      is the main factor for the counterparts. However, the continous DLC transfer
      layer was observed under PS solution, which make a lower COF of 0.08.

PMID- 25967040
TI  - sE-cadherin serves as a diagnostic and predictive parameter in prostate cancer
      patients.
AB  - BACKGROUND: Measurement of prostate-specific antigen (PSA) advanced the
      diagnostic and prognostic potential for prostate cancer (PCa). However, due to
      PSA's lack of specificity, novel biomarkers are needed to improve risk assessment
      and ensure optimal personalized therapy. A set of protein molecules as potential
      biomarkers was therefore evaluated in serum of PCa patients. METHODS: Serum
      samples from patients undergoing radical prostatectomy (RPE) for biopsy-proven
      PCa without neoadjuvant treatment were compared to serum samples from healthy
      subjects. Preliminary screening of 119 proteins in 10 PCa patients and 10
      controls was carried out by the Proteome Profiler Antibody Array. Those markers
      showing distinct differences between patients and controls were then further
      evaluated by ELISA in the serum of 165 PCa patients and 19 controls. Uni- and
      multivariate as well as correlation analysis were performed to test the
      capability of these molecules to detect disease and predict pathological outcome.
      RESULTS: Screening showed that soluble (s)E-cadherin, E-selectin, MMP2, MMP9,
      TIMP1, TIMP2, Galectin and Clusterin warranted further evaluation. sE-Cadherin,
      TIMP1, Galectin and Clusterin were significantly over- and MMP9 under-expressed
      in PCa compared to controls. The concentration of sE-cadherin, MMP2 and Clusterin
      correlated negatively and that of MMP9 and TIMP1 positively with the Gleason Sum
      at prostatectomy. Only sE-cadherin significantly correlated with the highest
      Gleason pattern. Compared to serum PSA, sE-cadherin provided an independent and
      better matching predictive ability for discriminating PCas with an upgrade at RPE
      and aggressive tumors with a Gleason Sum >=7. CONCLUSIONS: sE-cadherin performed
      most favorably from a large panel of serum proteins in terms of diagnostic and
      predictive potential in curatively treatable PCa. sE-cadherin merits further
      investigation as a biomarker for PCa.

PMID- 25967041
TI  - Inoculation of Phaseolus vulgaris with the nodule-endophyte Agrobacterium sp.
      10C2 affects richness and structure of rhizosphere bacterial communities and
      enhances nodulation and growth.
AB  - Agrobacterium sp. 10C2 is a nonpathogenic and non-symbiotic nodule-endophyte
      strain isolated from root nodules of Phaseolus vulgaris. The effect of this
      strain on nodulation, plant growth and rhizosphere bacterial communities of P.
      vulgaris is investigated under seminatural conditions. Inoculation with strain
      10C2 induced an increase in nodule number (+54 %) and plant biomass (+16 %).
      Grains also showed a significant increase in phosphorus (+53 %), polyphenols
      (+217 %), flavonoids (+62 %) and total antioxidant capacity (+82 %). The effect
      of strain 10C2 on bacterial communities was monitored using terminal restriction
      fragment length polymorphism of PCR-amplified 16S rRNA genes. When the initial
      soil was inoculated with strain 10C2 and left 15 days, the Agrobacterium strain
      did not affect TRF richness but changed structure. When common bean was sown in
      these soils and cultivated during 75 days, both TRF richness and structure were
      affected by strain 10C2. TRF richness increased in the rhizosphere soil, while it
      decreased in the bulk soil (root free). The taxonomic assignation of TRFs induced
      by strain 10C2 in the bean rhizosphere revealed the presence of four phyla
      (Firmicutes, Actinobacteria, Bacteroidetes and Proteobacteria) with a relative
      preponderance of Firmicutes, represented mainly by Bacillus species. Some of
      these taxa (i.e., Bacillus licheniformis, Bacillus pumilus, Bacillus
      senegalensis, Bacillus subtilis, Bacillus firmus and Paenibacillus koreensis) are
      particularly known for their plant growth-promoting potentialities. These results
      suggest that the beneficial effects of strain 10C2 observed on plant growth and
      grain quality are explained at least in part by the indirect effect through the
      promotion of beneficial microorganisms. 

PMID- 25967042
TI  - A co-expression network analysis reveals lncRNA abnormalities in peripheral blood
      in early-onset schizophrenia.
AB  - Long non-coding RNAs (lncRNAs) are emerging as important regulators of gene
      expression and disease processes especially in neuropsychiatric disorders. To
      explore the potential regulatory roles of lncRNAs in schizophrenia, we performed
      an integrated co-expression network analysis on lncRNA and mRNA microarray
      profiles generated from the peripheral blood samples in 19 drug-naive first
      episode early-onset schizophrenia (EOS) patients and 18 demographically matched
      typically developing controls (TDCs). Using weighted gene co-expression network
      analysis (WGCNA), we showed that the lncRNAs were organized into co-expressed
      modules, and two lncRNA modules were associated with EOS. The mRNA networks were
      constructed and three disease-associated modules were identified. Gene Ontology
      (GO) analysis indicated that the mRNAs were highly enriched for mitochondrion and
      related biological processes. Moreover, our results revealed a significant
      correlation between lncRNAs and mRNAs using the canonical correlation analysis
      (CCA). Our results suggest that the convergent lncRNA alteration may be involved
      in the etiologies of EOS, and mitochondrial dysfunction participates in the
      pathological process of the disease. Our findings may shed light on the
      pathogenesis of schizophrenia and facilitate future diagnosis and therapeutic
      strategies. 

PMID- 25967043
TI  - Patch testing in Australia: Is it adequate?
AB  - BACKGROUND/OBJECTIVES: Patch testing (PT) is essential for making the diagnosis
      of allergic contact dermatitis (ACD). However, the extent of PT undertaken by
      Australian dermatologists is unknown. The objectives of this study were to
      determine the rate and type of PT in Australia, the perceived obstacles to PT,
      and to explore the exposure to PT in dermatology training. METHODS: Data were
      collected on private PT (analysing Medicare item numbers) and public hospital
      based PT (estimated via verbal reports). An online survey on PT was sent to
      Fellows of the Australasian College of Dermatologists. RESULTS: It was found that
      total PT numbers, combining Medicare item number and public hospital data, were
      below the suggested optimum in all states and in Australia overall. Of the 173
      respondents to the survey, 61% reported they patch tested and 78% reported they
      referred for PT. TrueTest was the most commonly used PT system, although it is
      known to be inadequate. Dermatologists who PT as registrars were significantly
      more likely to PT as consultants (P value = 0.0029). Cost, expertise required and
      staffing were considered major obstacles to performing PT. Accessibility and cost
      to the patient were common obstacles to referral. CONCLUSIONS: The combination of
      suboptimal PT rates and inadequate PT means that patients are missing out on
      being diagnosed with ACD in Australia. Increasing the exposure of registrars to
      PT, supporting specialised centres, the development of the Australian Baseline
      Series and the Contact Allergen Bank will, it is hoped, improve the rates of
      comprehensive PT in Australia.

PMID- 25967044
TI  - BMP2 Regulation of CXCL12 Cellular, Temporal, and Spatial Expression is Essential
      During Fracture Repair.
AB  - The cellular and humoral responses that orchestrate fracture healing are still
      elusive. Here we report that bone morphogenic protein 2 (BMP2)-dependent fracture
      healing occurs through a tight control of chemokine C-X-C motif-ligand-12
      (CXCL12) cellular, spatial, and temporal expression. We found that the fracture
      repair process elicited an early site-specific response of CXCL12(+)-BMP2(+)
      endosteal cells and osteocytes that was not present in unfractured bones and
      gradually decreased as healing progressed. Absence of a full complement of BMP2
      in mesenchyme osteoprogenitors (BMP2(cKO/+)) prevented healing and led to a
      dysregulated temporal and cellular upregulation of CXCL12 expression associated
      with a deranged angiogenic response. Healing was rescued when BMP2(cKO/+) mice
      were systemically treated with AMD3100, an antagonist of CXCR4 and agonist for
      CXCR7 both receptors for CXCL12. We further found that mesenchymal stromal cells
      (MSCs), capable of delivering BMP2 at the endosteal site, restored fracture
      healing when transplanted into BMP2(cKO/+) mice by rectifying the CXCL12
      expression pattern. Our in vitro studies showed that in isolated endosteal cells,
      BMP2, while inducing osteoblastic differentiation, stimulated expression of
      pericyte markers that was coupled with a decrease in CXCL12. Furthermore, in
      isolated BMP2(cKO/cKO) endosteal cells, high expression levels of CXCL12
      inhibited osteoblastic differentiation that was restored by AMD3100 treatment or
      coculture with BMP2-expressing MSCs that led to an upregulation of pericyte
      markers while decreasing platelet endothelial cell adhesion molecule (PECAM).
      Taken together, our studies show that following fracture, a CXCL12(+)-BMP2(+)
      perivascular cell population is recruited along the endosteum, then a timely
      increase of BMP2 leads to downregulation of CXCL12 that is essential to determine
      the fate of the CXCL12(+)-BMP2(+) to osteogenesis while departing their
      supportive role to angiogenesis. Our findings have far-reaching implications for
      understanding mechanisms regulating the selective recruitment of distinct cells
      into the repairing niches and the development of novel pharmacological (by
      targeting BMP2/CXCL12) and cellular (MSCs, endosteal cells) interventions to
      promote fracture healing.

PMID- 25967045
TI  - Stroke-Risk Factors Differ between Rural and Urban Communities: Population Survey
      in Central Uganda.
AB  - BACKGROUND: Socioeconomic transition is changing stroke risk factors in Sub
      Saharan Africa. This study assessed stroke-risk factors and their associated
      characteristics in urban and rural Uganda. METHODS: We surveyed 5,420 urban and
      rural participants and assessed the stroke-risk factor prevalence and socio
      behavioural characteristics associated with risk factors. RESULTS: Rural
      participants were older with higher proportions of men and fewer poor compared to
      urban areas. The most prevalent modifiable stroke-risk factors in all areas were
      hypertension (27.1% rural and 22.4% urban, p = 0.004), overweight and obesity
      (22.0% rural and 42% urban, p < 0.0001), and elevated waist hip ratio (25.8%
      rural and 24.1% urban, p = 0.045). Diabetes, smoking, physical inactivity,
      harmful alcohol consumption were found in <=5%. Age, family history of
      hypertension, and waist hip ratio were associated with hypertension in all, while
      BMI, HIV were associated with hypertension only in urban dwellers. Sex and family
      history of hypertension were associated with BMI in all, while age, socio
      economic status and diabetes were associated with BMI only in urban dwellers.
      CONCLUSIONS: The prevalence of stroke-risk factors of diabetes, smoking,
      inactivity and harmful alcohol consumption was rare in Uganda. Rural dwellers
      belonging to a higher age group tended to be with hypertension and elevated waist
      hip ratio. Unlike high-income countries, higher socioeconomic status was
      associated with overweight and obesity.

PMID- 25967047
TI  - Molecular design, synthesis and evaluation of 2,3-diarylquinoxalines as estrogen
      receptor ligands.
AB  - Selective Estrogen Receptor Modulators (SERMs) are characteristically capable of
      being antagonist and agonist of estrogen receptors and, therefore, they can
      inhibit or stimulate estrogen production in different tissues. Aiming to
      contribute to the identification of new synthetic SERMs candidates, the basic
      skeletons of raloxifene and tamoxifene were used as model. Here of, a set of 2,3
      diaryl-quinoxalines having 2-(piperidin-1- yl)ethanol in the side chain have been
      synthesized and evaluated against human mammary carcinoma cells estrogen
      dependent (MCF-7), as well as in recombinant yeast assays (RYA) expressing
      estrogen receptor. Compound LSPN332 showed 40% inhibition of MCF-7 and EC50=290.6
      uM in RYA. The efficient synthesis of 2,3-diarylquinoxalines represents an
      excellent opportunity to identify new SERMs, and should therefore be of interest
      to the medicinal chemistry community. 

PMID- 25967046
TI  - Response-metrics for acute lung inflammation pattern by cobalt-based
      nanoparticles.
AB  - BACKGROUND: Although the surface area metric has been proposed as a possible dose
      metric for nanoparticles (NPs), it is limited to low-solubility NPs and the dose
      metric for high-solubility NPs is poorly understood. In this study, we aimed to
      assess the appropriate dose-metric or response-metric for NPs using two cobalt
      (Co)-based NPs, cobalt monoxide (CoO) and cobalt oxide (Co3O4), which both show
      distinctive solubility, and determine the role of their soluble Co ions in
      inflammation. METHODS: We evaluated the physicochemical properties of NPs,
      including solubility in artificial lysosomal fluid (ALF, pH 5.5). Acute lung
      inflammogenicity was evaluated by bronchoalveolar lavage fluid analysis using the
      rat intratracheal instillation model. The appropriate response-metric was then
      determined by plotting several dose-metrics against parameters for lung
      inflammation. To investigate the effect of the soluble fraction of CoO NPs, the
      equivalent doses of Co ions from CoCl2 were instilled. RESULTS: The Co3O4 and CoO
      NPs showed about 11.46% and 92.65% solubility in ALF, respectively. Instillation
      of Co3O4 NPs produced neutrophilic inflammation, but CoO NPs induced eosinophilic
      inflammation. The number of eosinophils showed good correlation with the soluble
      Co ions dose from NPs (r2=0.987, p<0.001), while the number of neutrophils showed
      good correlation with the surface area dose of the biopersistent NPs (r2=0.876,
      p<0.001). Instillation of CoCl2 showed a similar type and magnitude of
      inflammation as CoO NPs. CONCLUSIONS: In the Co-based NPs, the eosinophilic
      inflammation was produced by Co ions based on the ion metric, while the
      neutrophilic inflammation was developed based on the surface area metric of the
      biopersistent NPs.

PMID- 25967048
TI  - A Method to Predict the 3D Structure of an RNA Scaffold.
AB  - The ever increasing discoveries of noncoding RNA functions draw a strong demand
      for RNA structure determination from the sequence. In recently years,
      computational studies for RNA structures, at both the two-dimensional and the
      three-dimensional levels, led to several highly promising new developments. In
      this chapter, we describe a recently developed RNA structure prediction method
      based on the virtual bond-based coarse-grained folding model (Vfold). The main
      emphasis in the Vfold method is placed on the loop entropy calculations, the
      treatment of noncanonical (mismatch) interactions and the 3D structure assembly
      from motif-based template library. As case studies, we use the glycine riboswitch
      and the G310-U376 domain of MLV RNA to illustrate the Vfold-based prediction of
      RNA 3D structures from the sequences. 

PMID- 25967050
TI  - Expression and Purification of RNA-Protein Complexes in Escherichia coli.
AB  - For structural, biochemical or pharmacological studies, it is required to have
      pure RNA in large quantities. We previously devised a generic approach that
      allows efficient in vivo expression of recombinant RNA in Escherichia coli. We
      have extended the "tRNA scaffold" method to RNA/protein co-expression in order to
      express and purify RNA by affinity in native condition. As a proof-of-concept, we
      present the expression and the purification of the AtRNA-mala in complex with the
      MS2 coat protein. 

PMID- 25967051
TI  - Production of Homogeneous Recombinant RNA Using a tRNA Scaffold and Hammerhead
      Ribozymes.
AB  - Bacterial overproduction of recombinant RNA using a tRNA scaffold yields large
      amounts of chimeric RNA. For structural and functional characterizations of the
      RNA it is often necessary to remove the scaffold. Here we describe an efficient
      and facile method to release the RNA of interest from the tRNA scaffold by
      selective cleavage using cis-acting hammerhead ribozymes. After cleavage, the RNA
      of interest is purified to homogeneity using standard chromatographic and
      electrophoretic methods. Up to 5 mg of highly pure end-product RNA can be
      obtained from a single liter of bacterial culture. 

PMID- 25967049
TI  - Post-crystallization Improvement of RNA Crystal Diffraction Quality.
AB  - The crystallization and structural determination of large RNAs and their
      complexes remain major bottlenecks in the mechanistic analysis of cellular and
      viral RNAs. Here, we describe a protocol that combines post-crystallization
      dehydration and ion replacement that dramatically improved the diffraction
      quality of crystals of a large gene-regulatory tRNA-mRNA complex. Through this
      method, the resolution limit of X-ray data extended from 8.5 to 3.2 A, enabling
      structure determination. Although this protocol was developed for a particular
      RNA complex, the general importance of solvent and counterions in nucleic acid
      structure may render it generally useful for crystallographic analysis of other
      RNAs. 

PMID- 25967052
TI  - In Vivo Production of Small Recombinant RNAs Embedded in a 5S rRNA-Derived
      Protective Scaffold.
AB  - Preparative synthesis of RNA is a challenging task that is usually accomplished
      using either chemical or enzymatic polymerization of ribonucleotides in vitro.
      Herein, we describe an alternative approach in which RNAs of interest are
      expressed as a fusion with a 5S rRNA-derived scaffold. The scaffold provides
      protection against cellular ribonucleases resulting in cellular accumulations
      comparable to those of regular ribosomal RNAs. After isolation of the chimeric
      RNA from the cells, the scaffold can be removed if necessary by deoxyribozyme
      catalyzed cleavage followed by preparative electrophoretic separation of the
      cleavage reaction products. The protocol is designed for sustained production of
      high quality RNA on the milligram scale. 

PMID- 25967053
TI  - Detection of RNA-Protein Interactions Using Tethered RNA Affinity Capture.
AB  - Recent progress in large-scale nucleic acid analysis technology has revealed the
      presence of vast numbers of RNA species in cells, and extensive processing. To
      investigate the functions of these transcripts highly efficient methods are
      needed to analyze their interactions with RNA-binding proteins (RNBPs), and to
      understand the binding mechanisms. Many methods have been described to identify
      RNBPs, but none are wholly satisfactory, in part because RNAs are flexible
      macromolecules that adopt multiple conformations only some of which might bind to
      specific proteins. Here we describe a novel in vitro RNA-pull-down assay using
      tRNA scaffolded Streptavidin Aptamer (tRSA), to identify transcript specific RNA
      binding protein from mammalian cell lysates. The tRNA scaffold functions to
      stabilize the structure of the aptamer and the attached RNA, increasing the
      efficiency of the affinity purification. 

PMID- 25967054
TI  - A universal method for labeling native RNA in live bacterial cells.
AB  - The spectrum of RNA functions in the cell continues to widen and new types of RNA
      molecules continue to be discovered. However, methods to access and manipulate
      endogenous RNAs in live cells are limited. Here we describe a universal technique
      for labeling natural RNAs in live cells with the probes synthesized by the cell.
      The method is based on fluorescent protein complementation in combination with a
      split aptamer approach. Two RNA probes containing split aptamer sequences flanked
      with the antisense RNA target sequences are assembled on the target RNA to form a
      fluorescent ribonucleoprotein (RNP) complex. The mechanism of complex formation
      ensures highly sensitive RNA detection allowing visualization of endogenous
      bacterial mRNAs. We demonstrate the great potential of this method by detecting
      chromosomally low-level expressed unmodified bacterial mRNA in living bacterial
      cells. This method holds promise to become a broadly used tool in basic research,
      and eventually in diagnostics and therapeutics. 

PMID- 25967055
TI  - Live Cell Imaging Using Riboswitch-Spinach tRNA Fusions as Metabolite-Sensing
      Fluorescent Biosensors.
AB  - The development of fluorescent biosensors is motivated by the desire to monitor
      cellular metabolite levels in real time. Most genetically encodable fluorescent
      biosensors are based on receptor proteins fused to fluorescent protein domains.
      More recently, small molecule-binding riboswitches have been adapted for use as
      fluorescent biosensors through fusion to the in vitro selected Spinach aptamer,
      which binds a pro-fluorescent, cell-permeable small molecule mimic of the GFP
      chromophore, DFHBI. Here we describe methods to prepare and analyze riboswitch
      Spinach tRNA fusions for ligand-dependent activation of fluorescence in vivo.
      Example procedures describe the use of the Vc2-Spinach tRNA biosensor to monitor
      perturbations in cellular levels of cyclic di-GMP using either fluorescence
      microscopy or flow cytometry. The relative ease of cloning and imaging of these
      biosensors, as well as their modular nature, should make this method appealing to
      other researchers interested in utilizing riboswitch-based biosensors for
      metabolite sensing. 

PMID- 25967056
TI  - RNA Scaffold: Designed to Co-localize Enzymes.
AB  - Self-assembling RNA scaffold is designed to co-localize enzymes in engineered
      biological pathways through interactions between scaffold's protein docking
      domains and their affinity protein-enzyme fusions, in vivo. Here we introduced a
      noncoding RNA structure theophylline aptamer that respond to theophylline ligand
      in order to modulate RNA scaffold and regulate multistep enzymatic activities. We
      described the specifically designed RNA scaffold increased the fluorescent
      intensity in a splitting GFP assay by 2.25-fold, and also observed a 1.43-fold
      increase in multi-enzymatic efficiency in IAA synthesis pathway. 

PMID- 25967057
TI  - Artificial ligase ribozymes isolated by a "design and selection" strategy.
AB  - We developed a new in vitro selection strategy "design and selection" to isolate
      effectively artificial ribozymes (catalytic RNAs). An overall RNA structure
      (scaffold) is initially designed, and then a relatively short randomized sequence
      is installed at the reaction point of the scaffold, followed by the in vitro
      selection. This method can reduce the length of randomized sequence, providing
      large coverage of the sequence space in contrast with the conventional way, which
      makes the selection experiment effectively. Additionally, further analysis of
      ribozymes obtained by this approach is practically easy since the overall
      molecular structure is predesigned and well known. Here we show the procedure to
      isolate artificial RNA ligase ribozymes by this strategy. We have succeeded in
      isolation of the designed and selected ligase (DSL) ribozymes. 

PMID- 25967058
TI  - Engineering aptazyme switches for conditional gene expression in mammalian cells
      utilizing an in vivo screening approach.
AB  - Artificial RNA switches are an emerging class of genetic controllers suitable for
      synthetic biology applications. Aptazymes are fusions composed of an aptamer
      domain and a self-cleaving ribozyme. The utilization of aptazymes for conditional
      gene expression displays several advantages over employing conventional
      transcription factor-based techniques as aptazymes require minimal genomic space,
      fulfill their function without the need of protein cofactors, and most
      importantly are reprogrammable with respect to ligand selectivity and the RNA
      function to be regulated. Technologies that enable the generation of aptazymes to
      defined input ligands are of interest for the construction of biocomputing
      devices and biosensing applications. In this chapter we present a method that
      facilitates the in vivo screening of randomized pools of aptazymes in mammalian
      cells. 

PMID- 25967059
TI  - Aptazyme-based riboswitches and logic gates in mammalian cells.
AB  - This chapter describes a screening strategy to engineer synthetic riboswitches
      that can chemically regulate gene expression in mammalian cells. Riboswitch
      libraries are constructed by randomizing the key nucleotides that couple the
      molecular recognition function of an aptamer with the self-cleavage activity of a
      ribozyme. The allosteric ribozyme (aptazyme) candidates are cloned in the 3'
      untranslated region (UTR) of a reporter gene mRNA. The plasmid-encoded riboswitch
      candidates are transfected into a mammalian cell line to screen for the desired
      riboswitch function. Furthermore, multiple aptazymes can be cloned into the 3'
      UTR of a desired gene to obtain a logic gate response to multiple chemical
      signals. This screening strategy complements other methods to engineer robust
      mammalian riboswitches to control gene expression. 

PMID- 25967060
TI  - Design and Characterization of Topological Small RNAs.
AB  - RNA can self-assemble into complex structures through base pairing, as well as
      encode information and bind with proteins to induce enzymatic activity.
      Furthermore, RNA can possess intrinsic enzymatic-like (ribozymatic) activity, a
      property that, if necessary, can be activated only upon the binding of a small
      molecule or another RNA (as is the case in aptazymes). As such, RNA could be of
      use in nanotechnology as a programmable polymer capable of self-assembling into
      complex topological structures. In this chapter we describe a method for
      designing advanced topological structures using self-circulating RNA, exemplified
      by three tiers of topologically manipulated self-assembling synthetic RNA
      systems. The first tier of topological manipulation, the RNA knot is a physically
      locked structure, formed by circularizing one monomer of knotted single-stranded
      RNA left with loose ends (an "open" knot). The second tier, a two interlocking
      ring system, is made by interlocking two circular RNA components: a circular RNA
      target, and an RNA lasso designed to intercalate the target before circularizing.
      The third tier naturally extends this system into a string of topologically
      locked circular RNA molecules (an RNA chain). We detail the methodology used for
      designing such topologically complex RNAs, including computational predictions of
      secondary structure, and where appropriate, RNA-RNA interactions, illustrated by
      examples. We then describe the experimental methods used for characterizing such
      structures, and provide sequences of building blocks that can be used for
      topological manipulation of RNA. 

PMID- 25967061
TI  - Folding RNA-Protein Complex into Designed Nanostructures.
AB  - RNA-protein (RNP) complexes are promising biomaterials for the fields of
      nanotechnology and synthetic biology. Protein-responsive RNA sequences (RNP
      motifs) can be integrated into various RNAs, such as messenger RNA, short-hairpin
      RNA, and synthetic RNA nano-objects for a variety of purposes. Direct observation
      of RNP interaction in solution at high resolution is important in the design and
      construction of RNP-mediated nanostructures. Here we describe a method to
      construct and visualize RNP nanostructures that precisely arrange a target
      protein on the RNA scaffold with nanometer scale. High-speed AFM (HS-AFM) images
      of RNP nanostructures show that the folding of RNP complexes of defined sizes can
      be directly visualized at single RNP resolution in solution. 

PMID- 25967062
TI  - Simple Method for Constructing RNA Triangle, Square, Pentagon by Tuning Interior
      RNA 3WJ Angle from 60 degrees  to 90 degrees  or 108 degrees .
AB  - Precise shape control of architectures at the nanometer scale is an intriguing
      but extremely challenging facet. RNA has recently emerged as a unique material
      and thermostable building block for use in nanoparticle construction. Here, we
      describe a simple method from design to synthesis of RNA triangle, square, and
      pentagon by stretching RNA 3WJ native angle from 60 degrees  to 90 degrees  and
      108 degrees , using the three-way junction (3WJ) of the pRNA from bacteriophage
      phi29 dsDNA packaging motor. These methods for the construction of elegant
      polygons can be applied to other RNA building blocks including the utilization
      and application of RNA 4-way, 5-way, and other multi-way junctions. 

PMID- 25967063
TI  - RNA-Mediated CdS-Based Nanostructures.
AB  - The colloidal method provides an important tool to synthesize different
      nanostructures and their assemblies. The coating of colloidal inorganic
      nanostructures by the biotemplate of similar dimension not only provides them the
      thermodynamic stability but also imparts the chemical features to grow in
      different dimensionalities and capabilities for molecular recognition. In this
      chapter we describe detailed methodology for the synthesis and characterization
      of CdS nanoparticles templated by ribonucleic acid (RNA) derived from torula
      yeast. The binding of RNA passivates the surface of CdS nanostructures and
      controls their optical properties. The presence of excess Cd(2+) ions induces the
      folding and polarization in RNA-mediated CdS to enhance the supramolecular
      interactions among different building blocks. It produces CdS-based
      nanostructures of varied morphologies in the process of self-assembly. An
      interaction of the multi-functionalities of RNA with the excess Cd(2+)/Zn(2+)
      ions induces the spontaneous folding and polarization in RNA-mediated CdS/ZnS
      nanostructures and enhances the non-covalent bonding interactions among their
      building blocks. The self-organization in CdS/ZnS semiconducting nanosystem
      results in the production of novel tubular morphology. 

PMID- 25967064
TI  - An Effective Method for Specific Gene Silencing in Escherichia coli Using
      Artificial Small RNA.
AB  - Knockdown or silencing of a specific gene presents a powerful strategy for
      elucidating gene function in a variety of organisms. To date, efficient silencing
      methods have been established in eukaryotes, but not bacteria. In this chapter,
      an efficient and versatile gene silencing method using artificial small RNA
      (afsRNA) is described. For this purpose, target-recognizing sequences were
      introduced in specially designed RNA scaffolds to exist as single-stranded
      stretches in afsRNA. The translation initiation region of target genes was used
      as the sequence for afsRNA recognition, based on the theory that this site is
      usually highly accessible to ribosomes, and therefore, possibly, afsRNA. Two
      genes transcribed as monocistrons were tested with our protocol. Both genes were
      effectively silenced by their cognate afsRNAs.

PMID- 25967066
TI  - Method for analyzing left-censored bioassay data in large cohort studies.
AB  - In retrospective epidemiological studies of large cohorts of workers exposed to
      radioactive materials, it is often necessary to analyze large numbers of bioassay
      data sets containing censored values, or values recorded as less than a detection
      limit. Censored bioassay data create problems for all bioassay analysis methods,
      including analytical techniques based on least-squares regression to estimate
      intakes. A method is presented here that uses a simple empirically-derived
      equation for imputing replacement values for urine uranium concentration results
      reported as zero or less than a detection limit, that produces minimal bias in
      intakes estimated using least-square regression methods with the assumption of
      lognormally distributed measurement errors.

PMID- 25967067
TI  - An evaluation of the impact of flooring types on exposures to fine and coarse
      particles within the residential micro-environment using CONTAM.
AB  - Typical resuspension activities within the home, such as walking, have been
      estimated to contribute up to 25% of personal exposures to PM10. Chamber studies
      have shown that for moderate walking intensities, flooring type can impact the
      rate at which particles are re-entrained into the air. For this study, the impact
      of residential flooring type on incremental average daily (24 h) time-averaged
      exposure was investigated. Distributions of incremental time-averaged daily
      exposures to fine and coarse PM while walking within the residential micro
      environment were predicted using CONTAM, the multizone airflow and contaminant
      transport program of the National Institute of Standards and Technology.
      Knowledge of when and where a person was walking was determined by randomly
      selecting 490 daily diaries from the EPA's consolidated human activity database
      (CHAD). On the basis of the results of this study, residential flooring type can
      significantly impact incremental time-averaged daily exposures to coarse and fine
      particles (alpha=0.05, P<0.05, N=490, Kruskal-Wallis test) with high-density cut
      pile carpeting resulting in the highest exposures. From this study, resuspension
      from walking within the residential micro-environment contributed 6-72% of time
      averaged daily exposures to PM10.

PMID- 25967070
TI  - Comparison of WEB and Interactive Voice Response (IVR) Methods for Delivering
      Brief Alcohol Interventions to Hazardous-Drinking University Students: A
      Randomized Controlled Trial.
AB  - This study evaluated automated techniques including personalized normative
      feedback and protective behavioral strategies, for brief interventions intended
      to reduce peak alcohol concentrations in university students. After completing
      baseline assessment, a total of 1,678 hazardous-drinking consumers were
      randomized to a single or a repeated Internet (WEB) or Interactive Voice Response
      (IVR) intervention, or to a control group (Single WEB: 323; Single IVR: 329;
      Repeated WEB: 318; Repeated IVR: 334; CONTROL GROUP: 374). At follow-up, six
      weeks after baseline, questionnaires were returned by 1,422 participants (Single
      WEB: 277; Single IVR: 286; Repeated WEB: 259; Repeated IVR: 279; CONTROL GROUP:
      321). It was found that peak estimated BAC was reduced in the total group (b 
      0.14, 95% confidence interval (CI) -0.023; -0.005), in the total (b -0.17, 95% CI
      -0.027; -0.007) and single (b -0.021, 95% CI -0.032; -0.011) WEB group, and in
      the total (b -0.011, 95% CI -0.021; -0.015) and repeated (b -0.012, 95% CI 
      0.023; -0.000) IVR groups, compared to controls. The reduction in peak estimated
      BAC was greater in the single WEB group compared to the single IVR group (b 
      0.011, 95% CI -0.022; -0.000). This study concluded that both WEB and IVR
      interventions have a small but significant effect in reducing heavy episodic
      drinking, which may be due to the relatively large sample size. Repeated
      intervention may be needed if delivered by IVR.

PMID- 25967068
TI  - Biomonitoring and evaluation of permethrin uptake in forestry workers using
      permethrin-treated tick-proof pants.
AB  - We conducted a randomized case-control trial to analyze uptake of the
      insecticide/arcaricide permethrin in wearers of permethrin-impregnated and non
      impregnated pants in German forestry. Eighty-two male workers were each equipped
      for a 16-week period with permethrin-treated (test group) or with non-treated
      work pants (control group). Pants with or without lining to protect against cuts,
      obtained from two different distributors, were worn in each group. Urinary
      permethrin metabolite levels were measured by GC-MS/MS before, during and after
      wearing of the pants. Permethrin uptake was calculated using additional
      questionnaire data. In the control group, metabolite levels in the range of
      environmental background exposure (median: ~0.5 MUg/l) were measured. Subjects
      wearing impregnated pants showed consistently significantly higher exposure
      levels even before the first use of the pants with a maximum after 1 week of
      wearing the pants (median: ~12.5 MUg/l). Significant differences in internal
      exposure were found depending on which of the distributors the pants came from.
      Metabolite levels decreased probably due to permethrin losses associated with
      laundering the pants. Calculated permethrin uptake is below the value
      corresponding to the WHO-proposed acceptable daily intake. Based on our data, a
      marginally increased cancer risk compared with the general population cannot be
      excluded when wearing impregnated pants over a working-lifetime period.

PMID- 25967069
TI  - Developing a job-exposure matrix with exposure uncertainty from expert
      elicitation and data modeling.
AB  - Job exposure matrices (JEMs) are tools used to classify exposures for job titles
      based on general job tasks in the absence of individual level data. However,
      exposure uncertainty due to variations in worker practices, job conditions, and
      the quality of data has never been quantified systematically in a JEM. We
      describe a methodology for creating a JEM which defines occupational exposures on
      a continuous scale and utilizes elicitation methods to quantify exposure
      uncertainty by assigning exposures probability distributions with parameters
      determined through expert involvement. Experts use their knowledge to develop
      mathematical models using related exposure surrogate data in the absence of
      available occupational level data and to adjust model output against other
      similar occupations. Formal expert elicitation methods provided a consistent,
      efficient process to incorporate expert judgment into a large, consensus-based
      JEM. A population-based electric shock JEM was created using these methods,
      allowing for transparent estimates of exposure.

PMID- 25967071
TI  - Commentary: Forces That Drive the Vape Shop Industry and Implications for the
      Health Professions.
AB  - At least three factors may be driving the evolution of the vape shop industry, a
      rapidly growing market sector that specializes in the sales of electronic
      cigarettes: (1) the tobacco industry, (2) the public health sector and its
      diverse stakeholders, and (3) consumer demand. These influences and the responses
      of the vape shop sector have resulted in a rapidly changing landscape. This
      commentary briefly discusses these three factors and the implications for the
      health professions, as they address the vape shop industry and its consequences
      for public health.

PMID- 25967072
TI  - Brain correlates of alexithymia in eating disorders: A voxel-based morphometry
      study.
AB  - AIMS: Alexithymia is a personality trait that consists of difficulty in
      identifying and acknowledging one's own and others' feelings. Recent studies
      reported that alexithymia is present in both anorexia (AN) and bulimia nervosa
      (BN). Brain morphological studies on healthy subjects showed that alexithymia
      correlates with several brain regions involved in emotions processing. The aim of
      this study was to investigate the anatomical correlates of alexithymia in AN and
      BN. METHODS: We performed a voxel-based morphometry study on 21 patients with AN
      and 18 with BN. Seventeen healthy subjects were used as a control group.
      Alexithymia, depression and anxiety were assessed with self-administered
      questionnaires and correlated to gray matter (GM) density in each group. RESULTS:
      In BN, alexithymia was correlated with the GM of the parietal lobe, in particular
      of the right angular gyrus. The correlation was predominantly linked with
      Difficulty Describing Feelings. In AN, we did not find correlations between GM
      and alexithymia. CONCLUSIONS: In BN, our results support the hypothesis that this
      trait may represent a relevant pathogenic or maintenance factor that contributes
      to relational difficulties, present in this pathology. In AN, the lack of
      correlation between GM volume and alexithymia may be influenced by atrophy in
      several brain regions that in turn can be, as previously reported, a consequence
      of caloric restriction. Also, the nature of alexithymia may be different from
      that of BN and controls and this trait could be secondary to a psychopathologic
      process specific to AN.

PMID- 25967074
TI  - Clinical significance of CYP2C9-status guided valproic acid therapy in children.
AB  - OBJECTIVES: Valproic acid (VPA)-induced adverse effects, which are sometimes
      serious in children, can be associated with alterations in VPA metabolism. VPA
      evoked toxicity is attributed to both the parent compound and its unsaturated
      metabolites, primarily formed by the cytochrome P450 (CYP)2C9 enzyme. Thus,
      patients' CYP2C9-status may account for the predisposition to adverse reactions,
      and testing CYP2C9-status may contribute to the improvement and rationalization
      of VPA therapy in children. METHODS: In the CYPtest group, children's CYP2C9
      status was screened before initiating antiepileptic therapy. CYP2C9-status was
      estimated by the identification of defective CYP2C9 allelic variants (CYP2C9*2,
      CYP2C9*3) and current CYP2C9 expression in patients' leukocytes, which reflects
      hepatic CYP2C9 activities. When the results of CYP2C9 genotyping and CYP2C9
      expression were combined, the patients' VPA-metabolizing capacity was predicted,
      and VPA dosing was adjusted to the patients' CYP2C9-status. Clinical and
      biochemical parameters, such as VPA serum levels, blood cell counts, liver
      function parameters, and adverse effects in patients of CYPtest group were
      compared with those of the control group treated with VPA according to
      conventional clinical practice. RESULTS: CYP2C9-guided treatment significantly
      reduced VPA misdosing and consequently decreased the ratio of patients out of the
      range of target VPA blood concentrations. In the CYPtest group of children who
      received CYP2C9-status adapted dose, serum alkaline phosphatase (ALP) level and
      the ratio of patients with abnormal ALP levels were substantially lower than in
      the control group. The incidence of serious side effects, notably hyperammonemia,
      was reduced in the CYPtest group; however, some other side effects, such as
      weight changes and somnolence, could not be avoided. SIGNIFICANCE: The knowledge
      of pediatric patients' CYP2C9-status can contribute to the optimization of VPA
      dosing and to the avoidance of misdosing-induced side effects.

PMID- 25967073
TI  - Potential role of aspirin in the prevention of aneurysmal subarachnoid
      hemorrhage.
AB  - BACKGROUND: Inflammation is a key element behind the pathophysiology of cerebral
      aneurysm formation and rupture. Aspirin is a potent inhibitor of cyclooxygenase-2
      (COX), which plays a critical role in the expression of immune modulators known
      to contribute to cerebral aneurysm formation and rupture. Currently, there are no
      pharmacological therapies for patients with cerebral aneurysms. Both endovascular
      and microsurgical interventions may be associated with significant morbidity and
      mortality. Potentially, a medical alternative that prevents aneurysm progression
      and rupture may be a beneficial therapy for a significant number of patients.
      SUMMARY: In animal models, treatment with aspirin and genetic inactivation of COX
      2 decreases aneurysm formation and rupture. Selective inhibition of COX-1 did not
      decrease aneurysm rupture, suggesting that selection inhibition of COX-2 may be
      critical in thwarting aneurysm progression. Walls of ruptured human intracranial
      aneurysms have higher levels of COX-2 and microsomal prostaglandin E2 synthase 1
      (mPGES-1), both of which are known to be inhibited by aspirin. In a pilot study,
      patients undergoing microsurgical clipping had attenuated expression of COX-2,
      mPGES-1, and macrophages in aneurysm walls after 3 months of aspirin therapy
      versus those that did not receive aspirin. Additionally, in patients undergoing
      endovascular therapy, local circulating expression of chemokines and COX-2 were
      increased in blood samples taken from within aneurysm domes as compared to
      peripheral blood sample controls. Treatment with aspirin also resulted in
      decreased expression of COX-2 within leukocytes within aneurysms as compared to
      peripheral blood samples. Novel molecular imaging with ferumoxytol-enhanced MRI
      may help in the identification of patients at increased risk for aneurysm rupture
      and assessment of a response to aspirin therapy. Key Messages: Aspirin has been
      found to be a safe in patients harboring cerebral aneurysms and clinical studies
      provide evidence that it may decrease the overall rate of rupture. Furthermore,
      aspirin is an accessible and inexpensive medicine for patients who may not have
      access to endovascular or microsurgical treatment or for patients who are deemed
      low risk of aneurysm rupture, high risk for intervention, or both. Future
      clinical trials are indicated to determine the overall effect of aspirin on
      aneurysm progression and rupture. This review provides an update on the potential
      mechanisms and benefits of aspirin in the treatment of cerebral aneurysms.

PMID- 25967075
TI  - Hemoptysis in young adults.

PMID- 25967076
TI  - Effect of tiotropium on sputum and serum inflammatory markers and exacerbations
      in COPD.

PMID- 25967077
TI  - Outcomes for COPD pharmacological trials: From lung function to biomarkers.

PMID- 25967079
TI  - Smoking habits in sixth year medicine students and anti-smoking measures in
      Portugal.

PMID- 25967078
TI  - Bronchodilator responsiveness in patients with COPD (data from the UPLIFT trial).

PMID- 25967080
TI  - Smoking habits in sixth year medicine students and antismoking measures in
      Portugal.

PMID- 25967081
TI  - Ionic liquids as solvents of polar and non-polar solutes: affinity and
      coordination.
AB  - The use of ionic liquids (ILs) as highly tuneable solvents requires a deep
      understanding of the intermolecular interactions they can establish with the
      solutes. In the present work, we study the solvation patterns of two small but
      highly important molecules in the framework of IL properties and applications,
      namely H2O and CO2. Density functional theory (DFT) and ab initio molecular
      dynamics (AIMD) techniques are used for a systematic study of the interactions
      established between the solute and the solvent, identifying the influence of the
      non specific and specific interactions on the affinity of the IL for the solute,
      and how these interactions change with the surrounding environment. The nature,
      spatial distribution and strength of these interactions are described by means of
      topological analysis of the electronic density of the system. 

PMID- 25967082
TI  - The first report of human-derived G10 genotype of Echinococcus canadensis in
      China and possible sources and routes of transmission.
AB  - Cystic echinococcosis (CE) is one of the most important parasitic zoonoses. 10
      distinct genotypes, designated G1-G10 genotypes of Echinococcus granulosus sensu
      lato (s.l.), have been split into 4 species: Echinococcus granulosus sensu
      stricto (s.s.) (G1-G3), Echinococcus equinus (G4), Echinococcus ortleppi (G5) and
      Echinococcus canadensis (G6-G10); Echinococcus felidis has also been suggested as
      a sister taxon of E. granulosus s.s. recently. Four genotypes belonging to two
      species (G1 and G3 genotypes of E. granulosus s.s., and G6 and G7 genotypes of E.
      canadensis) have been identified in humans and animals in China. In the present
      study, a human-derived hydatid cyst from a patient in northeastern China's
      Heilongjiang Province was identified as G10 genotype of E. canadensis based on
      mitochondrial cytochrome c oxidase subunit I (cox1), cytochrome b (cytb) and NADH
      dehydrogenase subunit 1 (nad1) genes. Homology analysis showed the cox1 gene
      sequence of G10 genotype of E. canadensis had 100% homology with those from
      wolves in Mongolia and from a moose in Russia. The cytb and nad1 gene sequences
      of G10 genotype of E. canadensis had 100% homology with the complete sequence
      from a moose in Finland at an amino acid level. The infection source of the CE
      patient here might be primarily attributable to wolves. This is the first report
      of G10 genotype of E. canadensis in a human in China. The finding of G10 genotype
      of E. canadensis in China shows that this genotype possibly has a more wide
      geographical distribution than previously considered. 

PMID- 25967083
TI  - Stimulating the aberrant brain: Evidence for increased cortical hyperexcitability
      from a transcranial direct current stimulation (tDCS) study of individuals
      predisposed to anomalous perceptions.
AB  - Findings from neurological and clinical groups have shown that increased
      predisposition to anomalous experience/aura reflects an elevation in aberrant
      neural processes in the brain. However, studies of anomalous experiences in non
      clinical/non-neurological groups are less clear on this matter and are more
      typically confined to subjective questionnaire measures alone. The current
      investigation, the first to our knowledge, carried out a transcranial Direct
      Current Stimulation (tDCS) study of cortical hyperexcitability, and its
      association with anomalous experience in non-clinical/non-neurological groups.
      Sixty participants completed; (i) both excitatory (anodal) and inhibitory
      (cathodal) brain stimulation conditions of the visual cortex; (ii) a computerised
      pattern-glare task, where observers reported phantom visual distortions from
      viewing highly irritable visual patterns (a metric of cortical
      hyperexcitability), and; (iii) questionnaire measures of predisposition to
      anomalous perceptions. There were no reliable signs of cortical hyperexcitability
      (via pattern-glare tasks) when collapsed across the whole sample. However, a
      significant positive correlation between predisposition to anomalous experience
      and elevated signs of cortical hyperexcitability was observed. Crucially, there
      was a significant negative correlation between tDCS stimulatory conditions. A
      visual cortex that reacted more strongly to excitatory stimulation, responded
      less well to inhibitory suppression, and this pattern was related to
      predisposition to anomalous perceptions. Both findings are consistent with the
      presence of a hyperexcitable cortex. Collectively the present findings provide
      objective evidence that the brains of individuals predisposed to anomalous
      experiences/hallucinations can be hyperexcitable - even in the non-clinical/non
      neurological population. These data are consistent with continuum models of
      anomalous experience and have important implications for contemporary theories of
      aberrations in self-consciousness. 

PMID- 25967084
TI  - Responses in the right posterior superior temporal sulcus show a feature-based
      response to facial expression.
AB  - The face-selective region of the right posterior superior temporal sulcus (pSTS)
      plays an important role in analysing facial expressions. However, it is less
      clear how facial expressions are represented in this region. In this study, we
      used the face composite effect to explore whether the pSTS contains a holistic or
      feature-based representation of facial expression. Aligned and misaligned
      composite images were created from the top and bottom halves of faces posing
      different expressions. In Experiment 1, participants performed a behavioural
      matching task in which they judged whether the top half of two images was the
      same or different. The ability to discriminate the top half of the face was
      affected by changes in the bottom half of the face when the images were aligned,
      but not when they were misaligned. This shows a holistic behavioural response to
      expression. In Experiment 2, we used fMR-adaptation to ask whether the pSTS has a
      corresponding holistic neural representation of expression. Aligned or misaligned
      images were presented in blocks that involved repeating the same image or in
      which the top or bottom half of the images changed. Increased neural responses
      were found in the right pSTS regardless of whether the change occurred in the top
      or bottom of the image, showing that changes in expression were detected across
      all parts of the face. However, in contrast to the behavioural data, the pattern
      did not differ between aligned and misaligned stimuli. This suggests that the
      pSTS does not encode facial expressions holistically. In contrast to the pSTS, a
      holistic pattern of response to facial expression was found in the right inferior
      frontal gyrus (IFG). Together, these results suggest that pSTS reflects an early
      stage in the processing of facial expression in which facial features are
      represented independently. 

PMID- 25967085
TI  - How much is a word? Predicting ease of articulation planning from apraxic speech
      error patterns.
AB  - BACKGROUND: According to intuitive concepts, 'ease of articulation' is influenced
      by factors like word length or the presence of consonant clusters in an
      utterance. Imaging studies of speech motor control use these factors to
      systematically tax the speech motor system. Evidence from apraxia of speech, a
      disorder supposed to result from speech motor planning impairment after lesions
      to speech motor centers in the left hemisphere, supports the relevance of these
      and other factors in disordered speech planning and the genesis of apraxic speech
      errors. Yet, there is no unified account of the structural properties rendering a
      word easy or difficult to pronounce. AIM: To model the motor planning demands of
      word articulation by a nonlinear regression model trained to predict the
      likelihood of accurate word production in apraxia of speech. METHOD: We used a
      tree-structure model in which vocal tract gestures are embedded in hierarchically
      nested prosodic domains to derive a recursive set of terms for the computation of
      the likelihood of accurate word production. The model was trained with accuracy
      data from a set of 136 words averaged over 66 samples from apraxic speakers. In a
      second step, the model coefficients were used to predict a test dataset of
      accuracy values for 96 new words, averaged over 120 samples produced by a
      different group of apraxic speakers. RESULTS: Accurate modeling of the first
      dataset was achieved in the training study (R(2)adj = .71). In the cross
      validation, the test dataset was predicted with a high accuracy as well (R(2)adj
      = .67). The model shape, as reflected by the coefficient estimates, was
      consistent with current phonetic theories and with clinical evidence. In
      accordance with phonetic and psycholinguistic work, a strong influence of word
      stress on articulation errors was found. CONCLUSIONS: The proposed model provides
      a unified and transparent account of the motor planning requirements of word
      articulation.

PMID- 25967086
TI  - Dopamine enhances willingness to exert effort for reward in Parkinson's disease.
AB  - Parkinson's disease (PD) is traditionally conceptualised as a disorder of
      movement, but recent data suggest that motivational deficits may be more
      pervasive than previously thought. Here, we ask whether subclinical deficits in
      incentivised decision-making are present in PD and, if so, whether dopaminergic
      therapy ameliorates such deficits. We devised a novel paradigm in which
      participants decided whether they were willing to squeeze a hand-held dynamometer
      at varying levels of force for different magnitudes of reward. For each
      participant, we estimated the effort level at which the probability of accepting
      a reward was 50% - the effort 'indifference point'. Patients with PD (N = 26)
      were tested ON and OFF their usual dopaminergic medication, and their performance
      compared to those of age-matched controls (N = 26). No participant was clinically
      apathetic as defined by the Lille Apathy Rating Scale (LARS). Our data show that,
      regardless of medication status, patients with PD chose to engage less effort
      than controls for the lowest reward. Overall, however, dopamine had a motivating
      effect on participants' choice behaviour - patients with PD chose to invest more
      effort for a given reward when they were in the ON relative to OFF dopamine
      state. Importantly, this effect could not be attributed to motor facilitation. We
      conclude that deficits in incentivised decision-making are present in PD even in
      the absence of a clinical syndrome of apathy when rewards are low, but that
      dopamine acts to eliminate motivational deficits by promoting the allocation of
      effort. 

PMID- 25967087
TI  - Identification and expression analysis of BoMF25, a novel polygalacturonase gene
      involved in pollen development of Brassica oleracea.
AB  - KEY MESSAGE: BoMF25 acts on pollen wall. Polygalacturonase (PG) is a pectin
      digesting enzyme involved in numerous plant developmental processes and is
      described to be of critical importance for pollen wall development. In the
      present study, a PG gene, BoMF25, was isolated from Brassica oleracea. BoMF25 is
      the homologous gene of At4g35670, a PG gene in Arabidopsis thaliana with a high
      expression level at the tricellular pollen stage. Collinear analysis revealed
      that the orthologous gene of BoMF25 in Brassica campestris (syn. B. rapa) genome
      was probably lost because of genome deletion and reshuffling. Sequence analysis
      indicated that BoMF25 contained four classical conserved domains (I, II, III, and
      IV) of PG protein. Homology and phylogenetic analyses showed that BoMF25 was
      clustered in Clade F. The putative promoter sequence, containing classical cis
      acting elements and pollen-specific motifs, could drive green fluorescence
      protein expression in onion epidermal cells. Quantitative RT-PCR analysis
      suggested that BoMF25 was mainly expressed in the anther at the late stage of
      pollen development. In situ hybridization analysis also indicated that the strong
      and specific expression signal of BoMF25 existed in pollen grains at the mature
      pollen stage. Subcellular localization showed that the fluorescence signal was
      observed in the cell wall of onion epidermal cells, which suggested that BoMF25
      may be a secreted protein localized in the pollen wall.

PMID- 25967088
TI  - Participation rates for organized colorectal cancer screening programmes: an
      international comparison.
AB  - OBJECTIVE: Participation, an indicator of screening programme acceptance and
      effectiveness, varies widely in clinical trials and population-based colorectal
      cancer (CRC) screening programmes. We aimed to assess whether CRC screening
      participation rates can be compared across organized guaiac fecal occult blood
      test (G-FOBT)/fecal immunochemical test (FIT)-based programmes, and what factors
      influence these rates. METHODS: Programme representatives from countries
      participating in the International Cancer Screening Network were surveyed to
      describe their G-FOBT/FIT-based CRC screening programmes, how screening
      participation is defined and measured, and to provide participation data for
      their most recent completed screening round. RESULTS: Information was obtained
      from 15 programmes in 12 countries. Programmes varied in size, reach, maturity,
      target age groups, exclusions, type of test kit, method of providing test kits
      and use, and frequency of reminders. Coverage by invitation ranged from 30-100%,
      coverage by the screening programme from 7-67.7%, overall uptake/participation
      rate from 7-67.7%, and first invitation participation from 7-64.3%. Participation
      rates generally increased with age and were higher among women than men and for
      subsequent compared with first invitation participation. CONCLUSION: Comparisons
      among CRC screening programmes should be made cautiously, given differences in
      organization, target populations, and interpretation of indicators. More
      meaningful comparisons are possible if rates are calculated across a uniform age
      range, by gender, and separately for people invited for the first time vs.
      previously.

PMID- 25967089
TI  - [An introduction to patient reported outcome measures in quality assessment].
AB  - Patient reported outcome measures (PROM) have the potential to change how we
      measure quality in health care as well as promoting patient centered care. PROMs
      are any report of the status of a patient's health condition that comes directly
      from the patient, without interpretation of the patient's response by a clinician
      or anyone else. PROMs are used on an aggregated level to measure differences in
      quality between providers of health care. PROMs are also used on an individual
      level to address the patients' most bothersome needs. National consensus on
      development and implementation of PROM is needed. 

PMID- 25967090
TI  - [Status and perspectives on chronic myeloproliferative neoplasm treatment].
AB  - Polycythaemia vera, essential thrombocytosis and primary myelofibrosis are
      closely related, clonal myeloproliferative neoplasms. Our knowledge of the
      underlying molecular mechanisms driving these diseases has increased dramatically
      during the latest ten years. Traditionally, treatment of these malignancies has
      focused on lowering their inherent thromboembolic risk but with the discovery of
      the JAK2-V617F mutation and most recently the calreticulin mutations new
      therapeutic options such as interferon-alpha, JAK2-inhibitors and statins are
      being contemplated. This article reviews these new treatment options. 

PMID- 25967091
TI  - [New disease markers within the chronic myeloproliferative neoplasms].
AB  - The chaperone and calcium storing protein calreticulin is coded by CALR, and
      newly identified mutations in CALR are found in respectively 49-70% and 56-88% of
      JAK2- and MPL-negative patients with essential thrombocytaemia (ET) and primary
      myelofibrosis (PMF). A total of 41 mutations have been identified, all located to
      exon 9 which codes the protein's C-terminal. CALR mutations are present only in
      myeloid malignancies and confer a more indolent disease than JAK2-mutated ET and
      PMF. CALR mutations as a diagnostic and prognostic tool are promising and the
      mutations are potential targets for immune therapy. 

PMID- 25967092
TI  - [Coecum amoebiasis can be a rare manifestation of Entamoeba histolytica
      infection].
AB  - A 58-year-old Danish male was admitted to hospital with acute abdominal pain.
      Laparoscopy showed a normal appendix. However, a tumour in the ascending colon
      was found and hemicolectomy was performed. Pathological examination showed deep
      ulcerations with undermined edges and massive inflammation and necrosis. Periodic
      acid Schiff (PAS)-positive amoebae trophozoites were identified, and the patient
      was diagnosed with and treated for amoebiasis. The patient had not been abroad
      for 14 years but he worked with sewage. Patients in developed countries working
      with sewage should be considered at risk of developing amoebiasis. 

PMID- 25967093
TI  - Work-related rehabilitation aftercare for patients with musculoskeletal
      disorders: results of a randomized-controlled multicenter trial.
AB  - There is evidence that rehabilitation with a multidisciplinary focus on work
      related demands effectively improves work ability and quickens return to work in
      patients with musculoskeletal disorders. There could be benefits to the transfer
      of work-related components into rehabilitation aftercare. We examined the
      effectiveness of an intensified work-related rehabilitation aftercare program
      compared with standard intensified rehabilitation aftercare in Germany on work
      ability. We randomly assigned 307 patients with musculoskeletal disorders from 11
      rehabilitation centers to an aftercare program with work-related functional
      capacity training, work-related psychosocial groups, social counseling,
      relaxation training and exercise therapy (intervention group), or the usual
      aftercare program consisting of only exercise therapy (control group). The 6
      month follow-up questionnaire was completed by 78.5% of patients. There was no
      statistically relevant between-group difference in follow-up primary (work
      ability) and secondary outcomes (e.g. health-related quality of life, sick leave
      duration). Significant improvements were observed within both the intervention
      and the control groups. Severely disabled participants in the intervention group
      had better physical functioning and shorter sick leave duration after 6 months
      compared with severely disabled patients in the control group. A partial
      replacement of standard exercise therapy by a more work-related therapy does not
      seem to improve work ability superiorly. Improved aftercare treatment may require
      a focus on employer participation and involvement within the actual work
      environment. 

PMID- 25967094
TI  - Controlled implant/soft tissue interaction by nanoscale surface modifications of
      3D porous titanium implants.
AB  - Porous titanium implants are widely employed in the orthopaedics field to ensure
      good bone fixation. Recently, the use of porous titanium implants has also been
      investigated in artificial larynx development in a clinical setting. Such uses
      necessitate a better understanding of the interaction of soft tissues with porous
      titanium structures. Moreover, surface treatments of titanium have been generally
      evaluated in planar structures, while the porous titanium implants have complex 3
      dimensional (3D) architectures. In this study, the determining factors for soft
      tissue integration of 3D porous titanium implants were investigated as a function
      of surface treatments via quantification of the interaction of serum proteins and
      cells with single titanium microbeads (300-500 MUm in diameter). Samples were
      either acid etched or nanostructured by anodization. When the samples are used in
      3D configuration (porous titanium discs of 2 mm thickness) in vivo (in subcutis
      of rats for 2 weeks), a better integration was observed for both anodized and
      acid etched samples compared to the non-treated implants. If the implants were
      also pre-treated with rat serum before implantation, the integration was further
      facilitated. In order to understand the underlying reasons for this effect, human
      fibroblast cell culture tests under several conditions (directly on beads, beads
      in suspension, beads encapsulated in gelatin hydrogels) were conducted to mimic
      the different interactions of cells with Ti implants in vivo. Physical
      characterization showed that surface treatments increased hydrophilicity, protein
      adsorption and roughness. Surface treatments also resulted in improved adsorption
      of serum albumin which in turn facilitated the adsorption of other proteins such
      as apolipoprotein as quantified by protein sequencing. The cellular response to
      the beads showed considerable difference with respect to the cell culture
      configuration. When the titanium microbeads were entrapped in cell-laden gelatin
      hydrogels, significantly more cells migrated towards the acid etched beads. In
      conclusion, the nanoscale surface treatment of 3D porous titanium structures can
      modulate in vivo integration by the accumulative effect of the surface treatment
      on several physical factors such as protein adsorption, surface hydrophilicity
      and surface roughness. The improved protein adsorption capacity of the treated
      implants can be further exploited by a pre-treatment with autologous serum to
      render the implant surface more bioactive. Titanium microbeads are a good model
      system to observe these effects in a 3D microenvironment and provide a better
      representation of cellular responses in 3D. 

PMID- 25967095
TI  - Renoprotective Effects of Fenofibrate via Modulation of LKB1/AMPK mRNA Expression
      and Endothelial Dysfunction in a Rat Model of Diabetic Nephropathy.
AB  - This study was conducted to investigate whether the renoprotective effects of
      fenofibrate are mediated via attenuation of endothelial dysfunction and
      modulating the mRNA expression of adenosine monophosphate-activated protein
      kinase (AMPK) and its downstream kinase liver kinase B1 (LKB1) in rats with
      diabetic nephropathy (DN). Diabetes was induced by a single intraperitoneal
      injection of streptozotocin (55 mg kg(-1)). Fenofibrate (100 mg kg(-1), p.o.) was
      given to diabetic rats daily for 12 weeks. Treatment with fenofibrate
      significantly improved the renal function as revealed by the significant
      reductions in urinary albumin excretion and serum levels of creatinine and urea,
      in addition to the significant increase in creatinine clearance compared with the
      diabetic control group. Hyperglycemia-induced oxidative damage was ameliorated by
      treatment with fenofibrate as indicated by the significantly increased levels of
      glutathione and catalase together with the significant decrease in lipid
      peroxidation. Administration of fenofibrate caused significant increases in renal
      nitric oxide (NO) production and mRNA expression of endothelial NO synthase
      (eNOS), AMPK and LKB1, reflecting improvement of endothelial function. Our
      results give further insights into the mechanisms underlying the protective role
      of fenofibrate in DN via modulation of AMPK, LKB1 and eNOS mRNA expression.

PMID- 25967096
TI  - Control of the Normal and Pathological Development of Neural Stem and Progenitor
      Cells by the PC3/Tis21/Btg2 and Btg1 Genes.
AB  - The PC3/Tis21/Btg2 and Btg1 genes are transcriptional cofactors belonging to the
      Btg/Tob family, which regulate the development of several cell types, including
      neural precursors. We summarize here the actions of these genes on neural
      precursors in the adult neurogenic niches and the cognitive defects associated
      when their expression is altered. We consider also recent findings implicating
      them in neural and non-neural tumors, since common developmental mechanisms are
      involved. PC3/Tis21 is required for the regulation of the maturation of stem and
      progenitor cells in the adult dentate gyrus and subventricular zone (SVZ), by
      controlling both their exit from the cell cycle and the ensuing terminal
      differentiation. Such actions are effected by regulating the expression of
      several genes, including cyclin D1, BMP4, Id3. In cerebellar precursors, however,
      PC3/Tis21 regulates chiefly their migration rather than proliferation or
      differentiation, with important implications for the onset of medulloblastoma,
      the cerebellar tumor. In fact PC3/Tis21 is a medulloblastoma-suppressor, as its
      overexpression in cerebellar precursors inhibits this tumor; PC3/Tis21 shows anti
      tumor activity also in non-neural tumors. Btg1 presents a different functional
      profile, as it controls proliferation in adult stem/progenitor cells of dentate
      gyrus and SVZ, where is required to maintain their self-renewal and quiescence,
      but is apparently devoid of a direct control of their terminal differentiation or
      migration. Notably, physical exercise in Btg1-null mice rescues the loss of
      proliferative capability occurring in older stem cells. Both genes could be
      further investigated as therapeutical targets, namely, Btg1 in the process of
      aging and PC3/Tis21 as a tumor-suppressor.

PMID- 25967097
TI  - An overwhelmingly selective colorimetric sensor for Ag(+) using a simple modified
      polyacrylonitrile fiber.
AB  - A carboxymethyl-dithiocarbamate immobilized polyacrylonitrile fiber colorimetric
      sensor has been synthesized. This fiber sensor exhibits excellent selectivity and
      sensitivity for Ag(+) in aqueous solution with a remarkable color change from
      light pink to red-brown over a wide pH range of 2-12. The sensor responds
      selectively to Ag(+) in the presence of other ions, including Mg(2+), Al(3+),
      Ca(2+), Cr(3+), Mn(2+), Co(2+), Ni(2+), Cu(2+), Zn(2+), Cd(2+), Hg(2+) and
      Pb(2+). The colorimetric sensor has an extremely fast response time (10s) and a
      low visual limit of detection (5.53*10(-12) mol/L). The fiber sensor also
      undergoes an obvious color change in the presence of Ag(+) solutions containing
      EDTA, NaCl or NaBr. Density functional theory optimization reveals that the
      sensor and Ag(+) interact via a seven-membered ring complexation mechanism.

PMID- 25967098
TI  - The role of oxygen functional groups in the adsorption of heteroaromatic nitrogen
      compounds.
AB  - A wood-based activated carbon (AC) was oxidized using different oxidants. The
      resultant adsorbents were applied to adsorb nitrogen (N) containing compounds
      that appeared in light cycled oil. Appropriate oxidation treatment can increase
      oxygen functional groups on the surface of AC without much damage to its pore
      structure. Oxygen functional groups play a key role in enhancing adsorptive
      selectivity of carbons. Lactone groups can facilitate the selective removal of 1
      ring N compounds. Phenolic groups, total CO2-releasing groups and total O groups
      show an improvement in the adsorption of 2-ring N compounds. Aldehyde groups
      favor the adsorption of 3-ring and 4-ring N compounds. However, excessive
      oxidation can result in the collapse of pore structure and closure of pore
      channels. For instance, the carbon oxidized by a mixture of concentrated H2SO4
      and HNO3 has an extremely low adsorption performance. 

PMID- 25967099
TI  - Simultaneous nutrient removal, optimised CO2 mitigation and biofuel feedstock
      production by Chlorogonium sp. grown in secondary treated non-sterile saline
      sewage effluent.
AB  - The phycoremediation process has great potential for effectively addressing
      environmental pollution. To explore the capabilities of simultaneous algal
      nutrient removal, CO2 mitigation and biofuel feedstock production from spent
      water resources, a Chlorogonium sp. isolated from a tilapia pond in Hong Kong was
      grown in non-sterile saline sewage effluent for a bioremediation study. With high
      removal efficiencies of NH3-N (88.35+/-14.39%), NO3(-)-N (85.39+/-14.96%), TN
      (93.34+/-6.47%) and PO4(3-)-P (91.80+/-17.44%), Chlorogonium sp. achieved a CO2
      consumption rate of 58.96 mg L(-1) d(-1), which was optimised by the response
      surface methodology. Under optimised conditions, the lipid content of the algal
      biomass reached 24.26+/-2.67%. Overall, the isolated Chlorogonium sp. showed
      promising potential in the simultaneous purification of saline sewage effluent in
      terms of tertiary treatment and CO2 sequestration while delivering feedstock for
      potential biofuel production in a waste-recycling manner.

PMID- 25967100
TI  - Immunotherapy with liposome-bound TRAIL overcomes partial protection to soluble
      TRAIL-induced apoptosis offered by down-regulation of Bim in leukemic cells.
AB  - PURPOSE: Human Apo2-Ligand/TRAIL secreted by natural killer cells and cytotoxic T
      lymphocytes plays an important role immunosurveillance controlling tumor growth
      and metastasis. Moreover, the fact that Apo2L/TRAIL is capable of inducing cell
      death in tumor cells but not in normal cells makes this death ligand a promising
      anti-tumor agent. Previous data from our group demonstrated that Apo2L/TRAIL was
      physiologically released as transmembrane protein inserted in lipid vesicles,
      called exosomes. Recently, we demonstrated that artificial lipid nanoparticles
      coated with bioactive Apo2L/TRAIL (LUV-TRAIL) resembling the natural exosomes,
      greatly improved Apo2L/TRAIL activity and were able to induce apoptosis in
      hematological malignancies. In this study, we have deepened in the underlying
      mechanism of action of LUV-TRAIL in hematologic cells. METHODS/PATIENTS:
      Cytotoxic ability of LUV-TRAIL was assessed on Jurkat cells either over
      expressing the anti-apoptotic protein Mcl1 or down-regulating the pro-apoptotic
      protein Bim previously generated in our laboratory. We also tested LUV-TRAIL
      cytotoxic ability against primary human leukemic cells from T-cell ALL patient.
      RESULTS: Silencing Bim but not Mcl-1 over-expression partially protects Jurkat
      cells from apoptosis induced by sTRAIL. LUV-TRAIL induced caspase-8 and caspase-3
      activation and killed Jurkat-Mcl1 and Jurkat-shBim more efficiently than sTRAIL
      independently of the mitochondrial pathway. On the other hand, LUV-TRAIL were
      clearly more cytotoxic against primary leukemic cells from a T-cell ALL patient
      than sTRAIL. CONCLUSION: Tethering Apo2L/TRAIL to the surface of lipid
      nanoparticles greatly increases its bioactivity and could be of potential use in
      anti-tumor therapeutics.

PMID- 25967101
TI  - CtpA, a putative Mycobacterium tuberculosis P-type ATPase, is stimulated by
      copper (I) in the mycobacterial plasma membrane.
AB  - The transport of heavy-metal ions across the plasma membrane is essential for
      mycobacterial intracellular survival; in this context, P-type ATPases are pivotal
      for maintenance of ionic gradients and the plasma membrane homeostasis of
      mycobacteria. To date, the copper ion transport that is mediated by P-type
      ATPases in mycobacteria is poorly understood. In this work, the ion-specific
      activation of CtpA, a putative plasma membrane Mycobacterium tuberculosis P-type
      ATPase, with different heavy-metal cations was assessed. Mycobacterium smegmatis
      mc(2)155 cells heterologously expressing the M. tuberculosis ctpA gene displayed
      an increased tolerance to toxic levels of the Cu(2+) ion (4 mM) compared to
      control cells, suggesting that CtpA is possibly involved in the copper
      detoxification of mycobacterial cells. In contrast, the tolerance of M. smegmatis
      recombinant cells against other heavy-metal divalent cations, such as Co(2+),
      Mn(2+), Ni(2+) and Zn(2+), was not detected. In addition, the ATPase activity of
      plasma membrane vesicles that were obtained from M. smegmatis cells expressing
      CtpA was stimulated by Cu(+) (4.9 nmol of Pi released/mg of protein.min) but not
      by Cu(2+) ions; therefore, Cu(2+) reduction to Cu(+) inside mycobacterial cells
      is suggested. Finally, the plasma membrane vesicles of M. smegmatis that were
      enriched with CtpA exhibited an optimal activity at 37  degrees C and pH 7.9; the
      apparent kinetic parameters of the enzyme were a K(1/2) of 4.68 * 10(-2) uM for
      Cu(+), a Vmax of 10.3 U/mg of protein, and an h value of 1.91.

PMID- 25967102
TI  - Influence of preeclampsia and gestational obesity in maternal and newborn levels
      of vitamin D.
AB  - BACKGROUND: In recent years, a high prevalence of vitamin D deficiency amongst
      pregnant women and newborns has been observed throughout several regions of the
      world, especially in the presence of preeclampsia (PE) or obesity (OB). The aim
      of this study was to investigate whether nonobese and obese preeclamptic pregnant
      women and their newborns have low 25(OH)D compared with nonobese and obese
      nonpreeclamptic pregnant women; and to verify whether the maternal level of this
      vitamin correlates with the newborns' level. METHODS: This is a cross-sectional
      study conducted with 179 pregnant women recruited immediately before delivery,
      divided into four groups: PE(+)/OB(-); PE(+)/OB(+); PE(-)/OB(+); and PE(-)/OB(-),
      with gestational age >= 34 weeks. Maternal peripheral blood and newborns
      umbilical cord blood were collected and 25(OH)D levels were measured by
      chemiluminescence (LIAISON(r)). RESULTS: Infants born to preeclamptic mothers had
      a lower median 25(OH)D level than those born to nonpreeclamptic mothers (p <
      0.01). Obese pregnant women and their newborns had higher frequencies of 25(OH)D
      deficiency, but the difference with respect to nonobese pregnant women and their
      newborns was not significant. The vitamin D status of preeclamptic obese women
      was not worse than that of their nonobese counterparts. Newborns and maternal
      25(OH)D levels were significantly correlated (p = 0.01). Obesity weakened this
      correlation. CONCLUSIONS: Preeclamptic women and their newborns presented higher
      frequencies of 25(OH)D deficiency, but 25(OH)D levels were not significantly
      influenced by obesity. Obese pregnant women transferred less 25(OH)D to their
      fetuses.

PMID- 25967103
TI  - Simplified molecular input line entry system-based: QSAR modelling for MAP kinase
      interacting protein kinase (MNK1).
AB  - Quantitative structure-activity relationship (QSAR) models were built for the
      prediction of inhibition (pIC50, i.e. negative logarithm of the 50% effective
      concentration) of MAP kinase-interacting protein kinase (MNK1) by 43 potent
      inhibitors. The pIC50 values were modelled with five random splits, with the
      representations of the molecular structures by simplified molecular input line
      entry system (SMILES). QSAR model building was performed by the Monte Carlo
      optimisation using three methods: classic scheme; balance of correlations; and
      balance correlation with ideal slopes. The robustness of these models were
      checked by parameters as rm(2), r(*)m(2), [Formula: see text] and randomisation
      technique. The best QSAR model based on single optimal descriptors was applied to
      study in vitro structure-activity relationships of 6-(4-(2-(piperidin-1-yl)
      ethoxy) phenyl)-3-(pyridin-4-yl) pyrazolo [1,5-a] pyrimidine derivatives as a
      screening tool for the development of novel potent MNK1 inhibitors. The effects
      of alkyl group, -OH, -NO2, F, Cl, Br, I, etc. on the IC50 values towards the
      inhibition of MNK1 were also reported. 

PMID- 25967105
TI  - Decentralization and decision space in the health sector: a case study from
      Karnataka, India.
AB  - Various attempts have been made in India with respect to decentralization, most
      significantly the 73rd Amendment to the Constitution of India (1993) which
      provided the necessary legal framework for decentralization to take place.
      However, the outcome has been mixed: an evaluation of the impact of
      decentralization in the health sector found virtually no change in health system
      performance and access to health services in terms of availability of health
      personnel or improvement in various health indicators, such as Infant Mortality
      Rates or Maternal Mortality Ratio. Subsequently, there has been a conscious
      effort under the National Rural Health Mission (NRHM)-launched in 2005-to promote
      decentralization of funds, functions and functionaries to lower levels of
      government; and Karnataka had a head-start since devolution of all 29 functions
      prescribed by the 73rd Amendment had already taken place in the state by the late
      1990s. This study presents the findings of an on-going research effort to build
      empirical evidence on decentralization in the health sector and its impact on
      system performance. The focus here is on analyzing the responses of health
      personnel at the district level and below on their perceived 'Decision Space'-the
      range of choice or autonomy they see themselves as having along a series of
      functional dimensions. Overall, the data indicate that there is a substantial gap
      between the spirit of the NRHM guidelines on decentralization and the actual
      implementation on the ground. There is a need for substantial capacity building
      at all levels of the health system to genuinely empower functionaries,
      particularly at the district level, in order to translate the benefits of
      decentralization into reality.

PMID- 25967104
TI  - Reproducibility and clinical significance of pre-ovulatory serum progesterone
      level and progesterone/estradiol ratio on the day of human chorionic gonadotropin
      administration in infertile women undergoing repeated in vitro fertilization
      cycles.
AB  - BACKGROUND: The objective of this study was to explore the cycle-to-cycle
      reproducibility of serum progesterone level and progesterone/estradiol (P/E2)
      ratio in the final step of triggering oocyte maturation in patients undergoing
      repeated consecutive controlled ovarian hyperstimulation for in vitro
      fertilization (COH-IVF) treatment and to investigate the clinical parameters
      associated with serum progesterone concentration and P/E2 ratio. METHODS: We
      retrospectively studied 524 cycles in 203 infertile women who underwent two or
      more fresh COH-IVF cycles from July 1998 to May 2012 in a university hospital IVF
      unit. The patients were divided into groups according to the number (2, 3 or >=4)
      of total successive IVF cycles with successful oocyte retrieval. The within
      subject reproducibility of serum P and P/E2 was tested by calculating intra-class
      correlation coefficients (ICCs). Multiple linear regression analysis was used to
      assess the association between patient variables and pre-ovulatory serum P level
      and P/E2 ratio. RESULTS: The ICCs in women who underwent 2, 3 and >=4 IVF cycles
      were -0.052, 0.163 and 0.212, respectively, for serum P concentration and 0.180,
      0.168 and 0.148, respectively, for P/E2 ratio. All ICCs for both serum P and P/E2
      ratio were indicative of poor reproducibility. The number of oocytes was
      significantly positively related to P concentration, and endometrial thickness
      was significantly negatively related to P concentration and P/E2 ratio.
      CONCLUSION: The cycle-to-cycle reproducibility of pre-ovulatory serum P
      concentration and P/E2 ratio was poor in individual patients, and these
      fluctuations were more cycle- than patient-dependent. The number of oocytes was
      the most significant factor relating to P concentration. By using milder
      stimulation approach to produce fewer oocytes in the next cycle is a strategy to
      overcome the high serum P concentration, while clinicians should consider each
      patient's general condition including the age, ovarian reserve, embryo grading
      and the capacity of frozen-thawed embryo transfer.

PMID- 25967106
TI  - Betting Decision Under Break-Streak Pattern: Evidence from Casino Gaming.
AB  - Cognitive bias is prevalent among gamblers, especially those with gambling
      problems. Grounded in the heuristics theories, this study contributes to the
      literature by examining a cognitive bias triggered by the break streak pattern in
      the casino setting. We postulate that gamblers tend to bet on the latest outcome
      when there is a break-streak pattern. Moreover, three determinants of the betting
      decision under break-streak pattern, including the streak length of the
      alternative outcome, the frequency of the latest outcome, and gender, were
      identified and examined in this study. A non-participatory observational study
      was conducted among the Cussec gamblers in a casino in Macao. An analysis of 1229
      bets confirms our postulation, particularly when the streak of the alternative
      outcome is long, the latest outcome is frequent, and the gamblers are females.
      The findings provide meaningful implications for casino management and public
      policymakers regarding the minimization of gambling harm. 

PMID- 25967107
TI  - Retraction note: Gene expression profiles analysis identifies key genes for acute
      lung injury in patients with sepsis.

PMID- 25967108
TI  - The relevance of cell type- and tumor zone-specific VEGFR-2 activation in locally
      advanced colon cancer.
AB  - BACKGROUND: For the successful therapeutic use of inhibitors of the vascular
      endothelial growth factor receptor (VEGFR) pathway detailed knowledge of the
      mechanisms leading to tumor progression is indispensable. The main goal of this
      study was to determine the relevance of the VEGFR-2 activating pathway for colon
      carcinoma (CC) metastasis. The initial event is ligand-induced receptor
      activation through tyrosine autophosphorylation. METHODS: VEGFR-2, its ligands
      VEGF-C and VEGF-D and the phosphorylated (activated) receptor forms pVEGFR
      2(Tyr1175) and pVEGFR-2(Tyr1214) were investigated immunohistochemically in
      different tumor compartments (intratumoral (zone 1) - invasive front (zone 2) -
      extratumoral soft tissue (zone 3)) and various cell types (tumor cells,
      inflammatory cells, macro- and microvasculature) in 84 non-metastatic,
      lymphogenous-metastatic and haematogenous-metastatic CC. RESULTS: VEGF-D produced
      by tumor cells has an autocrine affinity for its receptor VEGFR-2. In tumor
      budding regions VEGF-D-induced receptor activation by autophosphorylation at
      Tyr1214 seems to be a possible initial event of the VEGFR-2-mediated signaling
      pathway, but without effect on metastatic behaviour. In inflammatory cells of
      almost all CC VEGFR-2 phosphorylation at Tyr 1175 and Tyr 1214 was detectable
      without accompanying receptor expression, suggesting receptor activation without
      cell surface expression. Peritumoral inflammatory cells also expressed paracrine
      acting VEGF-C. The autocrine VEGF-D/VEGFR-2 signaling axis and receptor
      autophosphorylation at Tyr1214 appear to be main events for capillaries in all
      three tumor zones and for small vessels in zone 1 and 2. Independent of the
      metastatic status a large number of cases with capillary immunopositivity in the
      angiogenically active invasive front was documented, especially for VEGF-D, VEGFR
      2 and pVEGFR-2(Tyr1214). VEGFR-2 positive extratumoral capillaries were
      significantly more common in distant metastatic CC. In all tumor compartments the
      investigated biomolecules were also detected in different frequencies in the
      macrovasculature, which is responsible for sufficient tumor vascularization. In
      addition, vascular paracrine-acting VEGF-C production was widely detected, but
      without zone and vessel-type dependence. CONCLUSIONS: The VEGFR-2 activating
      pathway is closely involved in tumor cell-associated, vessel-mediated and immuno
      inflammatory processes in colon carcinoma and appears to contribute to tumor
      survival and growth as well as maintenance of the infiltrative phenotype rather
      than to promote metastasis.

PMID- 25967109
TI  - Evaluating first trimester maternal serum screening combinations for Down
      syndrome suitable for use with reflexive secondary screening via sequencing of
      cell free DNA: high detection with low rates of invasive procedures.
AB  - OBJECTIVES: Examine primary Down syndrome screening using combinations of first
      trimester serum markers, with and without sequencing of cell free DNA as a
      secondary reflexive test. METHODS: Samples from 40 Down syndrome cases were
      matched with five control samples and tested for PAPP-A, free beta, AFP, inhibin
      A and PlGF. Results were converted to weight-adjusted multiples of the median
      (MoM) and population parameters computed. Monte Carlo simulation modeled Down
      syndrome detection and false positive rates for various marker combinations.
      After reflexive DNA testing, the revised detection and false positive rates were
      also computed. RESULTS: At a primary false positive rate of 20%, the baseline
      combination (maternal age, PAPP-A and free beta) detected 86.9%. Adding AFP or
      PlGF increased detection to 89.8% and 89.5%, respectively. Adding AFP and PlGF,
      AFP and inhibin-A, or all three markers, detected 93.7%, 94.1% and 95.5%,
      respectively. Modeling reflexive cf DNA testing results in little loss in
      detection (1%), but false positive rates fall to 0.2%. CONCLUSION: First
      trimester reflexive testing does not require nuchal translucency measurements,
      and has high detection and very low rates of invasive procedures. However, timing
      of DNA sample collection and the costs of sample collection and DNA testing need
      to be considered before implementation.

PMID- 25967110
TI  - Effects of stomata clustering on leaf gas exchange.
AB  - A general theoretical framework for quantifying the stomatal clustering effects
      on leaf gaseous diffusive conductance was developed and tested. The theory
      accounts for stomatal spacing and interactions among 'gaseous concentration
      shells'. The theory was tested using the unique measurements of Dow et al. (2014)
      that have shown lower leaf diffusive conductance for a genotype of Arabidopsis
      thaliana with clustered stomata relative to uniformly distributed stomata of
      similar size and density. The model accounts for gaseous diffusion: through
      stomatal pores; via concentration shells forming at pore apertures that vary with
      stomata spacing and are thus altered by clustering; and across the adjacent air
      boundary layer. Analytical approximations were derived and validated using a
      numerical model for 3D diffusion equation. Stomata clustering increases the
      interactions among concentration shells resulting in larger diffusive resistance
      that may reduce fluxes by 5-15%. A similar reduction in conductance was found for
      clusters formed by networks of veins. The study resolves ambiguities found in the
      literature concerning stomata end-corrections and stomatal shape, and provides a
      new stomata density threshold for diffusive interactions of overlapping vapor
      shells. The predicted reduction in gaseous exchange due to clustering, suggests
      that guard cell function is impaired, limiting stomatal aperture opening.

PMID- 25967111
TI  - Chloride Depletion Alkalosis as a Predictor of Inhospital Mortality in Patients
      with Decompensated Heart Failure.
AB  - OBJECTIVES: Chloride depletion alkalosis (CDA) is often seen as a consequence of
      diuresis in heart failure (HF) but its prognostic significance remains unknown.
      The purpose of this study was to evaluate the prognostic role of CDA in
      decompensated HF (DHF). METHODS: A retrospective cohort analysis was performed on
      674 patients who were admitted with DHF. Patients were assigned to 2 groups based
      on the change in serum bicarbonate (median = 3 mmol/l) after diuresis, which was
      calculated by computing the difference in the admission and discharge serum
      bicarbonate: the CDA group (a change in serum bicarbonate >=3 mmol/l) and the non
      CDA group (change in serum bicarbonate <3 mmol/l). The primary end points were
      inhospital mortality and the composite end point of all-cause 30-day mortality
      and hospital readmission for HF. RESULTS: In a multivariable logistic regression
      model, the CDA group, i.e. 374 patients, had a lower inhospital mortality than
      the non-CDA group, i.e. 300 patients (OR 0.11, 95% CI 0.03-0.38; p = 0.0005)
      after adjusting for other covariates. There was no statistically significant
      difference in the combined end point of all-cause 30-day mortality and
      readmission between the 2 groups (OR 1.26, 95% CI 0.74-2.12; p = 0.39).
      CONCLUSION: The presence of CDA during hospitalization for DHF was independently
      associated with a better inhospital survival rate.

PMID- 25967113
TI  - Copper-promoted sandmeyer difluoromethylthiolation of aryl and heteroaryl
      diazonium salts.
AB  - An efficient copper-promoted difluoromethylthiolation of aryl and heteroaryl
      diazonium salts is described. The reaction is conducted under mild reaction
      conditions and various functional groups were compatible. In addition, reactions
      of heteroaryl diazonium salts such as pyridyl, quinolinyl, benzothiazolyl,
      thiophenyl, carbazolyl, and pyrazolyl diazonium salts occurred smoothly to afford
      the medicinally important difluoromethylthiolated heteroarenes. Furthermore, a
      more practical one-pot direct diazotization and difluoromethylthiolation protocol
      was developed, and it converts the aniline derivatives into
      difluoromethylthiolated arenes. The utility of the method is demonstrated by
      difluoromethylthiolation of a number of natural products and drug molecules. 

PMID- 25967112
TI  - Triptolide improves systolic function and myocardial energy metabolism of
      diabetic cardiomyopathy in streptozotocin-induced diabetic rats.
AB  - BACKGROUND: Triptolide treatment leads to an improvement in Diabetic
      Cardiomyopathy (DCM) in streptozotocin-induced diabetic rat model. DCM is
      characterized by abnormal cardiac energy metabolism. We hypothesized that
      triptolide ameliorated cardiac metabolic abnormalities in DCM. We proposed (31)P
      nuclear magnetic resonance ((31)P NMR) spectrometry method for assessing cardiac
      energy metabolism in vivo and evaluating the effect of triptolide treatment in
      DCM rats. METHODS: Six weeks triptolide treatment was conducted on streptozotocin
      induced diabetic rats with dose of 100, 200 or 400 MUg/kg/day respectively. Sex-
      and age-matched non-diabetic rats were used as control group. Cardiac chamber
      dimension and function were determined with echocardiography. Whole heart
      preparations were perfused with Krebs-Henseleit buffer and (31)P NMR spectroscopy
      was performed. Cardiac p38 Mitogen Activating Protein Kinase (MAPK) was measured
      using real time PCR and western blot analysis. RESULTS: In diabetic rats, cardiac
      mass index was significantly higher, where as cardiac EF was lower than control
      group. (31)P NMR spectroscopy showed that ATP and pCr concentrations in diabetic
      groups were also remarkably lower than control group. Compared to non-treated
      diabetic rats, triptolide-treated diabetic groups showed remarkable lower cardiac
      mass index and higher EF, ATP, pCr concentrations, and P38 MAPK expressions. Best
      improvement was seen in group treated with Triptolide with dose 200 MUg/kg/day.
      CONCLUSIONS: (31)P NMR spectroscopy enables assessment of cardiac energy
      metabolism in whole heart preparations. It detects energy metabolic abnormalities
      in DCM hearts. Triptolide therapy improves cardiac function and increases cardiac
      energy metabolism at least partly through upregulation of MAPK signaling
      transduction.

PMID- 25967114
TI  - Inflammatory potential in relation to the microbial content of settled dust
      samples collected from moisture-damaged and reference schools: results of HITEA
      study.
AB  - Aiming to identify factors causing the adverse health effects associated with
      moisture-damaged indoor environments, we analyzed immunotoxicological potential
      of settled dust from moisture-damaged and reference schools in relation to their
      microbiological composition. Mouse RAW264.7 macrophages were exposed to settled
      dust samples (n = 25) collected from moisture-damaged and reference schools in
      Spain, the Netherlands, and Finland. After exposure, we analyzed production of
      inflammatory markers [nitric oxide (NO), tumor necrosis factor-alpha (TNF-)alpha,
      interleukin (IL)-6, and macrophage inflammatory protein (MIP)2] as well as
      mitochondrial activity, viability, apoptosis, and cell cycle arrest. Furthermore,
      particle counts, concentration of selected microbial groups as well as chemical
      markers such as ergosterol, 3-hydroxy fatty acids, muramic acid, endotoxins, and
      glucans were measured as markers of exposure. Dust from moisture-damaged schools
      in Spain and the Netherlands induced stronger immunotoxicological responses
      compared to samples from reference schools; the responses to Finnish samples were
      generally lower with no difference between the schools. In multivariate analysis,
      IL-6 and apoptosis responses were most strongly associated with moisture status
      of the school. The measured responses correlated with several microbial markers
      and numbers of particles, but the most important predictor of the
      immunotoxicological potential of settled dust was muramic acid concentration, a
      marker of Gram-positive bacteria.

PMID- 25967115
TI  - The Evaluation of Abnormal Voice Qualities in Patients with Amyotrophic Lateral
      Sclerosis.
AB  - OBJECTIVE: Voice abnormalities are among the symptoms occurring in patients with
      amyotrophic lateral sclerosis (ALS). They are divergent and range from
      hoarseness, through the excessive adduction of false folds, up to the weakness of
      the vocal folds. The aim of the study was to analyze the phonatory function of
      the larynx in ALS patients. METHODS: Seventeen patients with ALS were evaluated
      with subjective perceptual voice assessment (including the GRBAS scale),
      videolaryngostroboscopy including voice range and maximum phonation time (MPT),
      and objective acoustic voice analysis with IRIS software (including evaluation of
      jitter, shimmer, mean fundamental frequency, and noise-to-harmonics ratio (NHR)).
      Examinations were performed three times at 6-month intervals. RESULTS:
      Hoarseness, roughness, and breathiness of voice were all found more frequently in
      the majority of these patients. Voice range, amplitude of vibration, mucosal
      wave, and glottal closure showed significant abnormalities with repeated
      examinations. MPT was shortened especially among women with ALS. Acoustic
      analysis of voice among men showed increased jitter value in the first
      examination only, while jitter, shimmer, and NHR in women with ALS were increased
      in all examinations. CONCLUSIONS: Analysis of voice qualities among patients with
      ALS allows for the detection of various abnormalities associated with the natural
      progression of the disease.

PMID- 25967116
TI  - Aliphatic Polyethers: Classical Polymers for the 21st Century.
AB  - Polyethers-polymers with the structural element (R'-O-R)n in their backbone--are
      an old class of polymers which were already used at the time of the ancient
      Egyptians. However, still today these materials are highly important with
      applications in all areas of our life, reaching from the automotive and paper
      industry to cosmetics and biomedical applications. In this Review, different
      aliphatic polyethers like poly(epoxide)s, poly(oxetane)s, and
      poly(tetrahydrofuran) are discussed. Special emphasis is placed on the history,
      the polymerization techniques (industrially and in academia), the properties, the
      applications as well as recent developments of these materials.

PMID- 25967117
TI  - Heterogeneous effects of antiepileptic drugs in an in vitro epilepsy model--a
      functional multineuron calcium imaging study.
AB  - Epilepsy is a chronic brain disease characterised by recurrent seizures. Many
      studies of this disease have focused on local neuronal activity, such as local
      field potentials in the brain. In addition, several recent studies have
      elucidated the collective behavior of individual neurons in a neuronal network
      that emits epileptic activity. However, little is known about the effects of
      antiepileptic drugs on neuronal networks during seizure-like events (SLEs) at
      single-cell resolution. Using functional multineuron Ca(2+) imaging (fMCI), we
      monitored the activities of multiple neurons in the rat hippocampal CA1 region on
      treatment with the proconvulsant bicuculline under Mg(2+) -free conditions.
      Bicuculline induced recurrent synchronous Ca(2+) influx, and the events were
      correlated with SLEs. Other proconvulsants, such as 4-aminopyridine, pentetrazol,
      and pilocarpine, also induced synchronous Ca(2+) influx. We found that the
      antiepileptic drugs phenytoin, flupirtine, and ethosuximide, which have different
      mechanisms of action, exerted heterogeneous effects on bicuculline-induced
      synchronous Ca(2+) influx. Phenytoin and flupirtine significantly decreased the
      peak, the amount of Ca(2+) influx and the duration of synchronous events in
      parallel with the duration of SLEs, whereas they did not abolish the synchronous
      events themselves. Ethosuximide increased the duration of synchronous Ca(2+)
      influx and SLEs. Furthermore, the magnitude of the inhibitory effect of phenytoin
      on the peak synchronous Ca(2+) influx level differed according to the peak
      amplitude of the synchronous event in each individual cell. Evaluation of the
      collective behavior of individual neurons by fMCI seems to be a powerful tool for
      elucidating the profiles of antiepileptic drugs. 

PMID- 25967118
TI  - Using RecA protein to enhance kinetic rates of DNA circuits.
AB  - While DNA circuits are becoming increasingly useful as signal transducers, their
      utility is inhibited by their slow catalytic rate. Here, we demonstrate how RecA,
      a recombination enzyme that catalyzes sequence specific strand exchange, can be
      used to increase circuit rates up to 9-fold. We also show how the introduction of
      RNA into DNA circuits further controls the specificity of RecA strand exchange,
      improving signal-to-noise. 

PMID- 25967119
TI  - What effect do different 200 MUm laser fibres have on deflection and irrigation
      flow rates in a flexible ureterorenoscope?
AB  - The objective of the study is to evaluate the reduction in flow and scope
      deflection of four leading 200-MUm marketed laser fibres (Boston Scientific
      FlexivaTM 200, Boston Scientific FlexivaTM Trac Tip 200, Lumenis SlimLineTM EZ200
      and Optical Integrity ScopeSafeTM) via a flexible ureterorenoscope. A laboratory
      based bench test was performed using a Flex X2TM flexible ureterorenoscope. Mean
      upward/downward deflection angles and flow rates (ml/min) for each fibre were
      calculated and compared to a control. The Optical Integrity ScopeSafeTM fibre has
      the least loss of deflection, losing only 8 % upward and 6 % downward deflection.
      Deflection loss was significantly less with this fibre compared to all other
      fibres (p < 0.0001). Mean flow rates were significantly greater with the Optical
      Integrity ScopeSafeTM laser fibre at 23 ml/min (p < 0.0001). Despite all fibres
      marketed as 200 MUm, the deflection and flow properties show marked variations.
      The Optical Integrity ScopeSafeTM 200-MUm laser fibre offers the best overall
      performance with significantly improved flow rates and the least loss of scope
      deflection. 

PMID- 25967120
TI  - ADCK4-Associated Glomerulopathy Causes Adolescence-Onset FSGS.
AB  - Hereditary defects of coenzyme Q10 biosynthesis cause steroid-resistant nephrotic
      syndrome (SRNS) as part of multiorgan involvement but may also contribute to
      isolated SRNS. Here, we report 26 patients from 12 families with recessive
      mutations in ADCK4. Mutation detection rate was 1.9% among 534 consecutively
      screened cases. Patients with ADCK4 mutations showed a largely renal-limited
      phenotype, with three subjects exhibiting occasional seizures, one subject
      exhibiting mild mental retardation, and one subject exhibiting retinitis
      pigmentosa. ADCK4 nephropathy presented during adolescence (median age, 14.1
      years) with nephrotic-range proteinuria in 44% of patients and advanced CKD in
      46% of patients at time of diagnosis. Renal biopsy specimens uniformly showed
      FSGS. Whereas 47% and 36% of patients with mutations in WT1 and NPHS2,
      respectively, progressed to ESRD before 10 years of age, ESRD occurred almost
      exclusively in the second decade of life in ADCK4 nephropathy. However, CKD
      progressed much faster during adolescence in ADCK4 than in WT1 and NPHS2
      nephropathy, resulting in similar cumulative ESRD rates (>85% for each disorder)
      in the third decade of life. In conclusion, ADCK4-related glomerulopathy is an
      important novel differential diagnosis in adolescents with SRNS/FSGS and/or CKD
      of unknown origin. 

PMID- 25967121
TI  - Calcineurin and Sorting-Related Receptor with A-Type Repeats Interact to Regulate
      the Renal Na+-K+-2Cl- Cotransporter.
AB  - The furosemide-sensitive Na(+)-K(+)-2Cl(-)-cotransporter (NKCC2) is crucial for
      NaCl reabsorption in kidney thick ascending limb (TAL) and drives the urine
      concentrating mechanism. NKCC2 activity is modulated by N-terminal
      phosphorylation and dephosphorylation. Serine-threonine kinases that activate
      NKCC2 have been identified, but less is known about phosphatases that deactivate
      NKCC2. Inhibition of calcineurin phosphatase has been shown to stimulate
      transport in the TAL and the distal convoluted tubule. Here, we identified NKCC2
      as a target of the calcineurin Abeta isoform. Short-term cyclosporine
      administration in mice augmented the abundance of phospho-NKCC2, and treatment of
      isolated TAL with cyclosporine increased the chloride affinity and transport
      activity of NKCC2. Because sorting-related receptor with A-type repeats (SORLA)
      may affect NKCC2 phosphoregulation, we used SORLA-knockout mice to test whether
      SORLA is involved in calcineurin-dependent modulation of NKCC2. SORLA-deficient
      mice showed more calcineurin Abeta in the apical region of TAL cells and less
      NKCC2 phosphorylation and activity compared with littermate controls. In
      contrast, overexpression of SORLA in cultured cells reduced the abundance of
      endogenous calcineurin Abeta. Cyclosporine administration rapidly normalized the
      abundance of phospho-NKCC2 in SORLA-deficient mice, and a functional interaction
      between calcineurin Abeta and SORLA was further corroborated by binding assays in
      rat kidney extracts. In summary, we have shown that calcineurin Abeta and SORLA
      are key components in the phosphoregulation of NKCC2. These results may have
      clinical implications for immunosuppressive therapy using calcineurin inhibitors.

PMID- 25967122
TI  - Podocyte p53 Limits the Severity of Experimental Alport Syndrome.
AB  - Alport syndrome (AS) is one of the most common types of inherited nephritis
      caused by mutation in one of the glomerular basement membrane components. AS is
      characterized by proteinuria at early stage of the disease and glomerular
      hyperplastic phenotype and renal fibrosis at late stage. Here, we show that
      global deficiency of tumor suppressor p53 significantly accelerated AS
      progression in X-linked AS mice and decreased the lifespan of these mice. p53
      protein expression was detected in 21-week-old wild-type mice but not in age
      matched AS mice. Expression of proinflammatory cytokines and profibrotic genes
      was higher in p53(+/-) AS mice than in p53(+/+) AS mice. In vitro experiments
      revealed that p53 modulates podocyte migration and positively regulates the
      expression of podocyte-specific genes. We established podocyte-specific p53 (pod
      p53)-deficient AS mice, and determined that pod-p53 deficiency enhanced the AS
      induced renal dysfunction, foot process effacement, and alteration of gene
      expression pattern in glomeruli. These results reveal a protective role of p53 in
      the progression of AS and in maintaining glomerular homeostasis by modulating the
      hyperplastic phenotype of podocytes in AS. 

PMID- 25967124
TI  - Long-Term Neurodevelopmental Outcome of Children Treated with Tri-Iodothyronine
      after Cardiac Surgery: Follow-Up of a Double-Blind, Randomized, Placebo
      Controlled Study.
AB  - BACKGROUND: Transient thyroid dysfunction occurs in children after
      cardiopulmonary bypass (CPB). We demonstrated significant benefits of acute
      postoperative tri-iodothyronine (T3) treatment for recovery and myocardial
      function. Now we report the long-term neurodevelopment of these children.
      METHODS: Twenty-eight children (70% of the original study population) could be
      recruited for a follow-up examination (median age 10.7 years, range 10-19.6
      years) retaining the double-blind, randomized, placebo-controlled protocol.
      Cognitive function and motor development were tested, as were growth and thyroid
      and cardiac functions. RESULTS: The median full-scale intelligence quotient of
      all children was within the reference range and similar in the placebo and T3
      groups. Tests for motor and cognitive functions, growth, and thyroid and cardiac
      functions revealed concurrent results. CONCLUSIONS: Overall intellectual
      development is preserved in adolescents treated with CPB in infancy
      irrespectively of low postoperative thyroid hormone concentrations. While acute
      postoperative T3 treatment in children after CPB improves recovery, no
      significant long-term effects on neurodevelopment could be detected. We therefore
      speculate that transient postoperative thyroid dysfunction by means of
      nonthyroidal illness syndrome is predominantly mediated by extranuclear,
      nongenomic mechanisms and thus acutely affects the cardiovascular system but not
      the development of the central nervous system mediated by genomic mechanisms.

PMID- 25967123
TI  - Rationale and Approaches to Phosphate and Fibroblast Growth Factor 23 Reduction
      in CKD.
AB  - Patients with CKD often progress to ESRD and develop cardiovascular disease
      (CVD), yet available therapies only modestly improve clinical outcomes.
      Observational studies report independent associations between elevated serum
      phosphate and fibroblast growth factor 23 (FGF23) levels and risks of ESRD, CVD,
      and death. Phosphate excess induces arterial calcification, and although elevated
      FGF23 helps maintain serum phosphate levels in the normal range in CKD, it may
      contribute mechanistically to left ventricular hypertrophy (LVH). Consistent
      epidemiologic and experimental findings suggest the need to test therapeutic
      approaches that lower phosphate and FGF23 in CKD. Dietary phosphate absorption is
      one modifiable determinant of serum phosphate and FGF23 levels. Limited data from
      pilot studies in patients with CKD stages 3-4 suggest that phosphate binders, low
      phosphate diets, or vitamin B3 derivatives, such as niacin or nicotinamide, may
      reduce dietary phosphate absorption and serum phosphate and FGF23 levels. This
      review summarizes current knowledge regarding the deleterious systemic effects of
      phosphate and FGF23 excess, identifies questions that must be addressed before
      advancing to a full-scale clinical outcomes trial, and presents a novel
      therapeutic approach to lower serum phosphate and FGF23 levels that will be
      tested in the COMBINE Study: The CKD Optimal Management With BInders and
      NicotinamidE study. 

PMID- 25967125
TI  - MicroRNA-200c-141 and ?Np63 are required for breast epithelial differentiation
      and branching morphogenesis.
AB  - The epithelial compartment of the breast contains two lineages, the luminal- and
      the myoepithelial cells. D492 is a breast epithelial cell line with stem cell
      properties that forms branching epithelial structures in 3D culture with both
      luminal- and myoepithelial differentiation. We have recently shown that D492
      undergo epithelial to mesenchymal transition (EMT) when co-cultured with
      endothelial cells. This 3D co-culture model allows critical analysis of breast
      epithelial lineage development and EMT. In this study, we compared the microRNA
      (miR) expression profiles for D492 and its mesenchymal-derivative D492M.
      Suppression of the miR-200 family in D492M was among the most profound changes
      observed. Exogenous expression of miR-200c-141 in D492M reversed the EMT
      phenotype resulting in gain of luminal but not myoepithelial differentiation. In
      contrast, forced expression of ?Np63 in D492M restored the myoepithelial
      phenotype only. Co-expression of miR-200c-141 and ?Np63 in D492M restored the
      branching morphogenesis in 3D culture underlining the requirement for both
      luminal and myoepithelial elements for obtaining full branching morphogenesis in
      breast epithelium. Introduction of a miR-200c-141 construct in both D492 and
      D492M resulted in resistance to endothelial induced EMT. In conclusion, our data
      suggests that expression of miR-200c-141 and ?Np63 in D492M can reverse EMT
      resulting in luminal- and myoepithelial differentiation, respectively,
      demonstrating the importance of these molecules in epithelial integrity in the
      human breast. 

PMID- 25967126
TI  - JNK signaling is converted from anti- to pro-tumor pathway by Ras-mediated switch
      of Warts activity.
AB  - The c-Jun N-terminal kinase (JNK) pathway is a dual-functional oncogenic
      signaling that exerts both anti- and pro-tumor activities. However, the mechanism
      by which JNK switches its oncogenic roles depending on different cellular
      contexts has been elusive. Here, using the Drosophila genetics, we show that
      hyperactive Ras acts as a signaling switch that converts JNK's role from anti- to
      pro-tumor signaling through the regulation of Hippo signaling activity. In the
      normal epithelium, JNK signaling antagonizes the Hippo pathway effector Yorkie
      (Yki) through elevation of Warts activity, thereby suppressing tissue growth. In
      contrast, in the presence of hyperactive Ras, JNK signaling enhances Yki
      activation by accumulating F-actin through the activity of the LIM domain protein
      Ajuba, thereby promoting tissue growth. We also find that the epidermal growth
      factor receptor (EGFR) signaling uses this Ras-mediated conversion of JNK
      signaling to promote tissue growth. Our observations suggest that Ras-mediated
      switch of the JNK pathway from anti- to pro-tumor signaling could play crucial
      roles in tumorigenesis as well as in normal development. 

PMID- 25967127
TI  - In-Situ Fabrication of a Self-Aligned Selective Emitter Silicon Solar Cell Using
      the Gold Top Contacts To Facilitate the Synthesis of a Nanostructured Black
      Silicon Antireflective Layer Instead of an External Metal Nanoparticle Catalyst.
AB  - Silicon solar cells with nanopore-type black silicon (b-Si) antireflection (AR)
      layers and self-aligned selective emitter (SE) are reported in which the b-Si
      structure is prepared without the traditional addition of a nanoparticle (NP)
      catalyst. The contact-assisted chemical etching (CACE) method is reported here
      for the first time, in which the metal top contacts on silicon solar cell
      surfaces function as the catalysts for b-Si fabrication and the whole etching
      process can be done in minutes at room temperature. The CACE method is based on
      the metal-assisted chemical etching (MACE) solution but without or metal
      precursor in the Si etchant (HF:H2O2:H2O), and the Au top contacts, or catalysts,
      are not removed from the solar cell surface after the etching. The effects of
      etching time, HF and H2O2 concentration, and the HF:H2O2 ratio on the b-Si
      morphology, surface reflectivity, and solar cell efficiency have been
      investigated. Higher [HF] and [H2O2] with longer etching time cause collapse of
      the b-Si nanoporous structure and penetration of the p-n junctions, which are
      detrimental to the solar cell efficiency. The b-Si solar cell fabricated with the
      HF:H2O2:H2O volume ratio of 3:3:20 and a 3 min etch time shows the highest
      efficiency 8.99% along with a decrease of reflectivity from 36.1% to 12.6%
      compared to that of the nonetched Si solar cell. 

PMID- 25967128
TI  - Prenatal Identification of Pierre Robin Sequence: A Review of the Literature and
      Look towards the Future.
AB  - Fetal ultrasonography is an important tool used to prenatally diagnose many
      craniofacial conditions. Pierre Robin sequence (PRS) is a rare congenital
      deformation characterized by micrognathia, glossoptosis, and airway obstruction.
      PRS can present as a perinatal emergency when the retropositioned tongue
      obstructs the airway leading to respiratory compromise. More predictable and
      reliable diagnostic studies could help the treating medical team as well as
      families prepare for these early airway emergencies. The medical literature was
      reviewed for different techniques used to prenatally diagnose PRS radiologically.
      We have reviewed these techniques and suggested a possible diagnostic pathway to
      consistently identify patients with PRS prenatally. 

PMID- 25967130
TI  - Use of 18F-fluoride positron emission tomography as a predictor of the hip
      osteoarthritis progression.
AB  - OBJECTIVE: The prediction of hip osteoarthritis (OA) progression is still a
      difficult issue. We have adopted (18)F-fluoride positron emission tomography
      (PET) for the evaluation of hip osteoarthritis, and investigated the prediction
      utility of (18)F-fluoride PET for both pain worsening and OA progression using a
      logistic regression model. MATERIALS AND METHODS: A total of 57 hip joints were
      analyzed for progression risk factors for pain worsening and minimum joint space
      (MJS) narrowing by logistic regression analysis. Sex, age, BMI, existence of
      pain, the PET maximum standardized uptake value (SUV(max)), Kellgren and Lawrence
      grade, MJS, and follow-up period were used as explanatory variables. Receiver
      operating characteristic analysis was performed to calculate the cutoff value of
      the SUV(max). RESULTS: Multivariate logistic regression analysis revealed
      significant differences only in the SUV(max) values for pain worsening and MJS
      narrowing. The odds ratio of the SUV(max) for pain worsening was 1.89, and for
      MJS narrowing it was 11.02. The SUV(max) cutoff value was 7.2 (sensitivity: 1.00,
      specificity: 0.84) for pain worsening and 6.4 (sensitivity: 0.92, specificity:
      0.83) for MJS narrowing. CONCLUSIONS: Our results indicate that the PET SUV(max)
      is a best predictor of pain worsening and MJS narrowing. This imaging modality
      has a great potential for the prediction of OA progression.

PMID- 25967129
TI  - A retrospective study on the outcomes of MPO-ANCA-associated vasculitis in
      dialysis-dependent patients.
AB  - OBJECTIVES: This study investigated the clinical course of myeloperoxidase
      antineutrophil cytoplasm autoantibody (MPO-ANCA)-associated vasculitis after
      starting dialysis. METHODS: A retrospective review was conducted of the clinical
      charts of dialysis-dependent patients with MPO-ANCA-associated vasculitis who
      attended one of 8 associated clinics over the past 21 years. RESULTS: Eighty-nine
      patients were included in the study; 88 had microscopic polyangiitis (MPA) and 1
      had granulomatosis with polyangiitis. Of the 88 patients with MPA, 18 had renal
      limited vasculitis. Twenty-one relapses occurred among 13 patients (frequency,
      0.05 relapses/person-year; 95% confidence interval, 0.03-0.08). Mean time from
      start of dialysis to relapse was 65 +/- 59 months. Cox multivariate analysis
      showed that pulmonary involvement was a predictor of relapse (hazard ratio [HR],
      21.4) and mortality (HR, 4.60), and that patient age (HR, 1.10) and
      cyclophosphamide use (HR, 0.20) were significant predictors of mortality.
      Postdialysis 1- and 5-year survival rates were 83.0% and 65.6%, respectively;
      infection was the most frequent cause of death. CONCLUSION: Pulmonary involvement
      was a predictor of relapse and mortality. Although relapse can occur long after
      the start of dialysis, incidence was low among dialysis-dependent patients.
      Prolonged maintenance immunosuppressive therapy might be limited to patients with
      pulmonary involvement in dialysis-dependent ANCA-associated vasculitis.

PMID- 25967132
TI  - Factors affecting discontinuation of adalimumab and etanercept therapy in anti
      TNF-naive patients with ankylosing spondylitis: Nationwide population-based
      cohort study.
AB  - OBJECTIVES: We investigated factors associated with discontinuation of anti-tumor
      necrosis factor (TNF) therapy in patients with ankylosing spondylitis (AS), who
      were anti-TNF-naive and were given etanercept (ETN) or adalimumab (ADA). METHODS:
      This is a retrospective nationwide population-based cohort study. We identified
      1401 anti-TNF-naive patients with AS who initiated ETN (n = 441) or ADA (n = 960)
      and measured the duration of anti-TNF drug use. We recorded demographic and
      clinical data of all patients, and calculated adjusted hazard ratios (HRs) and
      95% confidence intervals (CIs) using Cox proportional hazard regression analyses.
      RESULTS: Overall, the ADA and ETN groups had similar risk for drug
      discontinuation (HR: 0.83; 95% CI: 0.63-1.08). In each group, concomitant use of
      methotrexate (MTX) or a non-steroidal anti-inflammatory drug was associated with
      a lower risk of discontinuation. Subgroup analysis indicated that concomitant MTX
      use reduced risk of discontinuation of ADA (HR: 0.54; 95% CI: 0.40-0.74), but not
      ETN (HR: 1.03; 95% CI: 0.65-1.63). CONCLUSIONS: This study of anti-TNF-naive
      patients with AS indicated that users of ADA and ETN had similar overall risk of
      drug discontinuation. However, patients taking ADA with MTX had a lower risk of
      discontinuation than those taking ADA alone.

PMID- 25967131
TI  - Prevalence of total knee arthroplasty and its predictive factors in Japanese
      patients with rheumatoid arthritis: Analysis using the NinJa cohort.
AB  - OBJECTIVES: The aim of this study was to clarify the prevalence and the
      predictive factors for undergoing total knee arthroplasty (TKA) among patients
      with rheumatoid arthritis (RA). METHODS: The data of 1,134 patients with RA who
      were enrolled in the Japanese nationwide cohort database NinJa in 2003 and
      consecutively followed up until 2009 were analyzed. RESULTS: Seventy-six patients
      underwent TKA during the observation period. The yearly progression of the
      modified Health Assessment Questionnaire or mHAQ score from 2003 to 2004, but not
      the yearly progression of the Disease Activity Score in 28 Joints or DAS28 or
      patient visual analog scale (VAS) score, was significantly higher in the patients
      who underwent TKA than those who did not. Multivariate analysis showed that knee
      involvement in the disease, high Steinbrocker stage (III or IV), and high patient
      VAS score at the time of enrollment were powerful predictive factors, with hazard
      ratios of 4.01, 3.71, and 1.20, respectively. According to survival analysis with
      TKA as an endpoint, patients with knee involvement in the disease at the time of
      enrollment had a significantly worse 5-year survival rate than did those without
      knee involvement (83.5% vs. 97.0%, respectively). CONCLUSION: Several factors
      were elucidated as predictive factors for undergoing TKA among patients with RA.

PMID- 25967133
TI  - Exploration of new drug-like inhibitors for serine/threonine protein phosphatase
      5 of Plasmodium falciparum: a docking and simulation study.
AB  - Protein phosphorylation is an important mechanism that implicates in physiology
      of any organism including parasitic protozoa. Metallic protein Ser/Thr protein
      phosphatase 5 (PP5) controls various cellular signaling pathways of Plasmodium
      falciparum. The structure and inhibitory mechanism of PP5 in P. falciparum is not
      known. In fact, no experimental structural data are available for P. falciparum
      Ser/Thr protein phosphatase 5 (PfPP5) till date. Hence, we have proposed computer
      generated model of catalytic subunit of PfPP5 and its inhibitory mechanism was
      analyzed. A set of 42 known natural inhibitors of protein phosphate family were
      docked against metal-binding catalytic site of PfPP5 and we found that
      cantharidin and its derivatives shows better binding energy among them.
      Similarity search was performed by taking these compounds as lead compounds
      against PubChem and ChemBank. The search result provides 3703 similar compounds;
      out of which 2245 qualified the Lipinski rule of five. Further, virtual screening
      of these compounds was performed and selected top 25 were selected on the basis
      of binding energy. In continuation, rigid and flexible docking of these screened
      compounds was performed to get the insight of interactions. Finally, top 5
      compounds were verified for ADMET properties, and then, all are subjected to MD
      simulations for 25 ns in order to validate their stability. Compounds CBI:
      3554182, CID: 23561913, and CID: 21168680 showed most stable binding, although
      some of hydrogen bonds pairing varied throughout simulation. These finding would
      be helpful to the medicinal chemists for the development of antimalarial drugs to
      combat this deadly disease.

PMID- 25967135
TI  - Equine Genital Squamous Cell Carcinoma: In Situ Hybridization Identifies a
      Distinct Subset Containing Equus caballus Papillomavirus 2.
AB  - Equus caballus papillomavirus 2 (EcPV2) has been proposed as an etiologic agent
      for genital squamous cell carcinoma (SCC), the most common malignant tumor of the
      horse penis. EcPV2 is commonly detected by polymerase chain reaction (PCR) on
      normal horse genitalia; therefore, unraveling the virus' role in oncogenic
      transformation requires other methods of detection. In this study, a highly
      sensitive multiple-probe chromogenic in situ hybridization (ISH) technique was
      designed to recognize the E6/E7 oncogenes of EcPV2. ISH demonstrated abundant
      virus within 6 of 13 penile and preputial SCCs, whereas evidence of solar damage
      was found in 6 cases that were negative for EcPV2 by ISH. The ISH technique is
      valuable for studies of pathogenesis, since it demonstrates for the first time
      that the vast majority of neoplastic cells contain virus. Moreover, hybridization
      was present in all metastases examined, implying stability of E6/E7 expression in
      these clonal populations of neoplastic cells. This study contributes to the
      accumulating evidence for a causal role of EcPV2 in a subset of genital SCCs in
      horses. 

PMID- 25967134
TI  - Multiple clinical episodes of Plasmodium falciparum malaria in a low transmission
      intensity setting: exposure versus immunity.
AB  - BACKGROUND: Epidemiological studies indicate that some children experience many
      more episodes of clinical malaria than their age mates in a given location.
      Whether this is as a result of the micro-heterogeneity of malaria transmission
      with some children effectively getting more exposure to infectious mosquitoes
      than others, or reflects a failure in the acquisition of immunity needs to be
      elucidated. Here, we investigated the determinants of increased susceptibility to
      clinical malaria by comparing the intensity of exposure to Plasmodium falciparum
      and the acquisition of immunity in children at the extreme ends of the over
      dispersed distribution of the incidence of clinical malaria. METHODS: The study
      was nested within a larger cohort in an area where the intensity of malaria
      transmission was low. We identified children who over a five-year period
      experienced 5 to 16 clinical malaria episodes (children at the tail-end of the
      over-dispersed distribution, n = 35), remained malaria-free (n = 12) or had a
      single episode (n = 26). We quantified antibodies against seven Plasmodium
      falciparum merozoite antigens in plasma obtained at six cross-sectional surveys
      spanning these five years. We analyzed the antibody responses to identify
      temporal dynamics that associate with disease susceptibility. RESULTS: Children
      experiencing multiple episodes of malaria were more likely to be parasite
      positive by microscopy at cross-sectional surveys (X (2) test for trend 14.72 P =
      0.001) and had a significantly higher malaria exposure index, than those in the
      malaria-free or single episode groups (Kruskal-Wallis test P = 0.009). In
      contrast, the five-year temporal dynamics of anti-merozoite antibodies were
      similar in the three groups. Importantly in all groups, antibody levels were
      below the threshold concentrations previously observed to be correlated with
      protective immunity. CONCLUSIONS: We conclude that in the context of a low
      malaria transmission setting, susceptibility to clinical malaria is not accounted
      for by anti-merozoite antibodies but appears to be a consequence of increased
      parasite exposure. We hypothesize that intensive exposure is a prerequisite for
      protective antibody concentrations, while little to modest exposure may manifest
      as multiple clinical infections with low levels of antibodies. These findings
      have implications for interventions that effectively lower malaria transmission
      intensity.

PMID- 25967136
TI  - Characterization of Spontaneous Mammary Tumors in Domestic Djungarian Hamsters
      (Phodopus sungorus).
AB  - Mammary tumors that spontaneously occurred in domestic Djungarian hamsters
      (Phodopus sungorus) were histologically examined. Forty-five mammary tumors
      included 14 adenomas, 18 adenocarcinomas, 1 lipid-rich carcinoma, 2
      adenoacanthomas, 2 malignant adenomyoepitheliomas, 1 benign mixed tumor, and 7
      "balloon cell" carcinosarcomas. The latter 4 types were newly recognized
      neoplasms in Djungarian hamsters. The relatively high incidence of spontaneous
      mammary carcinosarcomas in domestic Djungarian hamsters is intriguing.
      Carcinosarcomas exhibited anomalous histological features made up of a mixture of
      glandular cells, polygonal cells (including "balloon cells"), and sarcomatous
      spindle cells in varying proportions. Transitional features from glandular cells
      to polygonal cells and subsequently to sarcomatous spindle cells were observed.
      Using immunohistochemistry, we observed that glandular cells exhibited an
      epithelial phenotype (cytokeratin(+)/vimentin(-)), spindle cells exhibited a
      mesenchymal phenotype (cytokeratin(-)/vimentin(+)), and polygonal cells exhibited
      an intermediate phenotype (cytokeratin(+)/vimentin(+)). Reduction or loss of beta
      catenin expression and gain of S100A4 expression were observed in polygonal and
      spindle cells. The polygonal cell population included a varying number of
      characteristic cells that were expanded by large intracytoplasmic vacuoles.
      Electron microscopy revealed that these "balloon cells" had large cytoplasmic
      lumens lined by microvilli. These observations suggest that epithelial
      mesenchymal transition may account for the pathogenesis of mammary
      carcinosarcomas in Djungarian hamsters. 

PMID- 25967137
TI  - Cluster of Acute Toxicity from Ingestion of Synthetic Cannabinoid-Laced Brownies.
AB  - INTRODUCTION: Synthetic cannabinoid receptor agonists (SCRAs) are emerging
      designer drugs of abuse. Most reports on the health effects of these drugs are
      case reports. Unlike SCRAs, marijuana has classically been used via many routes
      of exposure including oral, such as in brownies. We report on 11 symptomatic
      patients who unknowingly ingested brownies laced with analytically confirmed SCRA
      and presented with mostly neuropsychiatric and cardiovascular symptoms. CASE
      SERIES: All 11 patients were taken to the ED within 1 h of exposure with the
      onset of various symptoms. There were five males and six females, age range 20-57
      years. Neuropsychiatric and cardiovascular symptoms predominated: memory
      impairment (91 %, 10/11) and inappropriate giggling (36 %, 4/11). All the
      patients had light-headedness, perioral and facial numbness and tingling
      sensation, dry mouth, difficulty focusing/blurring of vision, and sluggishness.
      No patient had depressed consciousness. Two patients had heart rates >100, and 4
      of 11 (36 %) had BP >140/80. One patient had chest pain. All the symptoms were
      completely resolved 4 h following their onset except two patients who had ongoing
      weakness and fatigue. All patients had negative urine drugs of abuse immunoassays
      and ethanol, acetaminophen, and salicylate concentrations, as well as normal
      electrocardiograms (ECGS) and metabolic panels. The SCRA was confirmed to be AM
      2201. All the patients were discharged from the ED in stable condition within 10
      h of the exposure. CONCLUSION: Oral exposure of 11 patients to brownies laced
      with analytically confirmed SCRA resulted in neuropsychiatric and cardiovascular
      symptoms. This series reflects that like marijuana, oral exposures to SCRAs can
      lead to symptoms.

PMID- 25967138
TI  - Latest approaches for the treatment of obesity.
AB  - INTRODUCTION: Obesity is a body weight disorder characterized by excess adiposity
      that increases the risk for developing co-morbidities such as type 2 diabetes. A
      large medical need exists for new anti-obesity treatments capable of promoting
      10% or greater weight loss, with minimal side effects. AREAS COVERED: The authors
      describe the application of monogenic forms of rare obesity and genome-wide
      association studies in selecting critical pathways for drug discovery.
      Furthermore, they review in detail several pathways and pharmacological targets
      in the central nervous system (e.g., the leptin-melanocortin axis, the opioid
      system, GLP-1/GLP-1 system, and FGF21/FGFR1c/beta-Klotho axis) that play an
      important role in the regulation of feeding behavior and energy homeostasis.
      Special focus is given to new strategies that engage well-known targets via novel
      mechanisms in order to circumvent issues seen with previous drug candidates that
      failed in the clinic. Finally, the authors discuss the recent developments around
      fixed-dose combinations, targeted polypharmacology, and non-traditional
      combinations of drugs and devices. EXPERT OPINION: The future for new weight-loss
      approaches to treat obesity looks promising. Current therapies have shown modest
      effects on weight loss in the general obese population but will have greater
      impact in smaller homogeneous sub-populations of obese subjects using
      personalized medicine. Drug combinations that target multiple, complementary
      pathways have the potential to promote double-digit weight loss in a broader,
      heterogeneous patient population. Furthermore, the development of advanced
      subcutaneous delivery technologies has opened up opportunities to develop
      breakthrough peptide and biologic agents for the treatment of obesity.

PMID- 25967139
TI  - Application of a Three-Dimensional Reconstruction Technique in Liver
      Autotransplantation for End-Stage Hepatic Alveolar Echinococcosis.
AB  - BACKGROUND: The purpose of this study was to determine the clinical value of
      three-dimensional (3D) computer reconstruction technology in pre-operative
      assessment and surgical planning for liver autotransplantation in patients with
      end-stage hepatic alveolar echinococcosis (HAE). STUDY DESIGN: Fifteen end-stage
      HAE patients received surgical treatment in our hospital between May 2011 and
      July 2014. 3D reconstruction and virtual surgeries were performed on diseased
      livers using a 3D reconstruction system for liver (IQQA-Liver). The feasibility
      and safety of liver autotransplantation were assessed for successful
      implementation of surgery. The results were compared with intraoperative
      conditions and computed tomography (CT) to verify the accuracy of pre-operative
      evaluation. RESULTS: Fifteen patients underwent liver resections and liver
      autotransplantation using surgical strategies consistent with pre-operative
      surgical planning in 3D reconstruction. Furthermore, there was no significant
      difference between whole-liver volume (2848.26 +/- 798.41 vs. 2598.70 +/- 822.45
      cm(3), t = -4.635, P > 0.05) and lesion volume (1159.09 +/- 789.47 vs. 1213.14 +/
      813.76 cm(3), t = -1.959, P > 0.05) measured by 3D and traditional two
      dimensional (2D) manual tracing from CT. The remaining liver volumes calculated
      by 3D and 2D CT were 810.47 +/- 214.05 and 892.00 +/- 262.36 cm(3) (t = -3.275, P
      > 0.05), with an average error rate of 6.2 and 16.5%, respectively. The pre
      operative remaining liver volumes estimated by the two methods were positively
      correlated with the actual weight (783.67 +/- 217.74 g) after the surgery (r
      three-dimensional = 0.976, r multislice CT = 0.883, P < 0.01). CONCLUSIONS: An
      individualized liver reconstruction technique can provide comprehensive anatomic
      information on livers of patients with end-stage HAE. Pre-operative virtual
      surgery can effectively improve the success rate of liver autotransplantation and
      reduce the risks of surgery.

PMID- 25967140
TI  - Comparison of Endoscopic Vacuum Therapy Versus Stent for Anastomotic Leak After
      Esophagectomy.
AB  - BACKGROUND: Endoscopic vacuum therapy is a novel option for the management of
      esophageal leaks. This study compares endoscopic vacuum therapy versus placement
      of covered stents for anastomotic leaks after esophagectomy. METHODS: N = 45
      consecutive patients with anastomotic leaks following esophagectomy (including
      patients referred to our center from other hospitals for complication management)
      were managed by endoscopic therapy at our institution from January 2009 to
      February 2015. Outcomes of stent and endoscopic vacuum therapy were analyzed
      retrospectively. RESULTS: Thirty patients received endoscopic stent placement and
      15 endoscopic vacuum therapy. In the stent group, seven patients were switched to
      endoscopic vacuum and four to surgery. Classified by type of initial endoscopic
      therapy, the success rate (anastomotic healing, patient recovered) was higher for
      endoscopic vacuum therapy (endoscopic vacuum 93.3%, stent 63.3 %; p = 0.038).
      Classified by final endoscopic therapy (after switches in therapy), success rates
      were 86.4 and 60.9% (p = 0.091), respectively. There was no difference observed
      in mortality, duration of therapy, and length of hospital stay between the study
      groups. CONCLUSIONS: Endoscopic vacuum therapy might be more effective than
      endoscopic stent placement in the management of esophageal anastomotic leaks.

PMID- 25967141
TI  - Adenosquamous Carcinoma of the Esophagus and Esophagogastric Junction: Clinical
      Manifestations and Treatment Outcomes.
AB  - BACKGROUND/AIMS: The aim of this study is to understand the clinicopathological
      manifestations, treatment, and prognostic factors of adenosquamous carcinoma
      (ASC) of the esophagus and esophagogastric junction, a rare malignancy. METHODS:
      From 1981 to 2011, 26 out of 4704 patients (23 males, 3 females; mean age: 65.8
      years) with ASC of the esophagus and esophagogastric junction who received
      surgical resection were analyzed. RESULTS: Only one (4.2%) patient was diagnosed
      with ASC by preoperative endoscopic biopsy. Three patients received Ivor-Lewis
      operation with intrathoracic esophagogastrostomy, seven received gastrectomies,
      and the other 16 underwent transthoracic esophagectomies. Median follow-up time
      was 30.6 months (interquartile range, 17.9-95.1 months). At study end, there were
      12 (46.2%) patients with tumor relapse, all within 3 years postoperatively. The 5
      year disease-free survival (DFS) rate was 46.2%. Tumor length and no
      postoperative adjuvant treatment were the independent prognostic factors for DFS.
      The 5-year overall survival (OS) rate was 30.8%. On multivariate analysis, the
      resection type, tumor length, and perineural invasion were independent prognostic
      factors for OS. CONCLUSION: ASC is a rare cell type of the esophagus and
      esophagogastric junction that is easily misdiagnosed at endoscopic biopsy. OS
      rate was no worse than that reported for squamous cell carcinoma (SCC). Tumor
      length was the independent prognostic factor for both DFS and OS.

PMID- 25967142
TI  - TLR9-Targeted STAT3 Silencing Abrogates Immunosuppressive Activity of Myeloid
      Derived Suppressor Cells from Prostate Cancer Patients.
AB  - PURPOSE: Recent advances in immunotherapy of advanced human cancers underscored
      the need to address and eliminate tumor immune evasion. The myeloid-derived
      suppressor cells (MDSC) are important inhibitors of T-cell responses in solid
      tumors, such as prostate cancers. However, targeting MDSCs proved challenging due
      to their phenotypic heterogeneity. EXPERIMENTAL DESIGN: Myeloid cell populations
      were evaluated using flow cytometry on blood samples, functional assays, and
      immunohistochemical/immunofluorescent stainings on specimens from healthy
      subjects, localized and metastatic castration-resistant prostate cancer patients.
      RESULTS: Here, we identify a population of Lin(-)CD15(HI)CD33(LO) granulocytic
      MDSCs that accumulate in patients' circulation during prostate cancer progression
      from localized to metastatic disease. The prostate cancer-associated MDSCs
      potently inhibit autologous CD8(+) T cells' proliferation and production of
      IFNgamma and granzyme-B. The circulating MDSCs have high levels of activated
      STAT3, which is a central immune checkpoint regulator. The granulocytic pSTAT3(+)
      cells are also detectable in patients' prostate tissues. We previously generated
      an original strategy to silence genes specifically in Toll-like Receptor-9 (TLR9)
      positive myeloid cells using CpG-siRNA conjugates. We demonstrate that human
      granulocytic MDSCs express TLR9 and rapidly internalize naked CpG-STAT3siRNA,
      thereby silencing STAT3 expression. STAT3 blocking abrogates immunosuppressive
      effects of patients-derived MDSCs on effector CD8(+) T cells. These effects
      depended on reduced expression and enzymatic activity of Arginase-1, a downstream
      STAT3 target gene and a potent T-cell inhibitor. CONCLUSIONS: Overall, we
      demonstrate the accumulation of granulocytic MDSCs with prostate cancer
      progression and the feasibility of using TLR9-targeted STAT3siRNA delivery
      strategy to alleviate MDSC-mediated immunosuppression.

PMID- 25967145
TI  - Molecular Pathways: Targeting Tumor-Infiltrating Myeloid-Derived Suppressor Cells
      for Cancer Therapy.
AB  - Tumor-infiltrating myeloid-derived suppressor cells (MDSC) are a heterogeneous
      and immunosuppressive cell subset that blocks the proliferation and the activity
      of both T and natural killer (NK) cells and promotes tumor vasculogenesis and
      progression. Recent evidences demonstrate that the recruitment of MDSCs in tumors
      also blocks senescence induced by chemotherapy promoting chemoresistance. Hence,
      the need of novel therapeutic approaches that can efficiently target MDSC
      recruitment and function in cancer. Among them, novel combinatorial treatments of
      chemotherapy and immunotherapy or treatments that induce depletion of MDSCs in
      peripheral sites should be taken in consideration.

PMID- 25967144
TI  - Vaccination with Melanoma Helper Peptides Induces Antibody Responses Associated
      with Improved Overall Survival.
AB  - PURPOSE: A melanoma vaccine incorporating six peptides designed to induce helper
      T-cell responses to melanoma antigens has induced Th1-dominant CD4(+) T-cell
      responses in most patients, and induced durable clinical responses or stable
      disease in 24% of evaluable patients. The present study tested whether this
      vaccine also induced antibody (Ab) responses to each peptide, and whether Ab
      responses were associated with T-cell responses and with clinical outcome.
      EXPERIMENTAL DESIGN: Serum samples were studied from 35 patients with stage III
      IV melanomas vaccinated with 6 melanoma helper peptides (6MHP). IgG Ab responses
      were measured by ELISA. Associations with immune response and overall survival
      were assessed by log-rank test and chi(2) analysis of Kaplan-Meier data. RESULTS:
      Ab responses to 6MHP were detected by week 7 in 77% of patients, and increased to
      peak 6 weeks after the last vaccine and persisted to 6 months. Ab responses were
      induced most frequently to longer peptides. Of those with T-cell responses, 82%
      had early Ab responses. Survival was improved for patients with early Ab response
      (P = 0.0011) or with early T-cell response (P < 0.006), and was best for those
      with both Ab and T-cell responses (P = 0.0002). CONCLUSIONS: Vaccination with
      helper peptides induced both Ab responses and T-cell responses, associated with
      favorable clinical outcome. Such immune responses may predict favorable clinical
      outcome to guide combination immunotherapy. Further studies are warranted to
      understand mechanisms of interaction of these Abs, T-cell responses, and tumor
      control.

PMID- 25967143
TI  - Effects of Adjuvant Sorafenib and Sunitinib on Cardiac Function in Renal Cell
      Carcinoma Patients without Overt Metastases: Results from ASSURE, ECOG 2805.
AB  - PURPOSE: Sunitinib and sorafenib are used widely in the treatment of renal cell
      carcinoma (RCC). These agents are associated with a significant incidence of
      cardiovascular (CV) dysfunction and left ventricular ejection fraction (LVEF)
      declines, observed largely in the metastatic setting. However, in the adjuvant
      population, the CV effects of these agents remain unknown. We prospectively
      defined the incidence of cardiotoxicity among resected, high-risk RCC patients
      treated with these agents. EXPERIMENTAL DESIGN: Sunitinib, sorafenib, or placebo
      was administered for up to 12 months in patients with high-risk, resected RCC.
      LVEF was measured by multigated acquisition (MUGA) scans at standard intervals.
      Additional CV adverse events were reported according to NCI Common Terminology
      Criteria for Adverse Events (CTCAE). RESULTS: Among 1,943 patients randomized,
      1,599 had at least 1 post-baseline MUGA. Within 6 months, 21 patients (1.3%)
      experienced a cardiac event, defined as an LVEF decline from baseline that was
      >15% and below the institutional lower limit of normal. Nine of 513 patients
      (1.8%) were on sunitinib, 7 of 508 (1.4%) on sorafenib, and 5 of 578 (0.9%) on
      placebo (P = 0.28 and 0.56 comparing sunitinib and sorafenib to placebo,
      respectively). With dose interruption or adjustment, 16 of the 21 recovered their
      LVEF to >50%. The incidence of symptomatic heart failure, arrhythmia, or
      myocardial ischemia did not differ among groups. CONCLUSIONS: In the adjuvant
      setting, we prospectively define low incidence of cardiotoxicity with sunitinib
      and sorafenib. These findings may be related to close CV monitoring, or
      potentially to fewer CV comorbidities in our nonmetastatic population.

PMID- 25967146
TI  - Quality of life and functioning in first-episode psychosis Chinese patients with
      different antipsychotic medications.
AB  - AIM: This study compared the quality of life and functioning of 285 first-episode
      psychosis Chinese patients with different antipsychotic medications in Hong Kong.
      METHOD: Under the Jockey Club Early Psychosis project, a total of 285 patients
      were recruited from all inpatient and outpatient psychiatric units in Hong Kong
      between 2009 and 2011. In addition to the medication information, patients were
      assessed with the Scale for the Assessment of Positive Symptoms, the Scale for
      the Assessment of Negative Symptoms, the Udvalg for Kliniske Undersogelser (UKU),
      Barnes Akathisia Rating Scale (BARS), the Social and Occupational Functioning
      Assessment Scale (SOFAS), the Role Functioning Scale, and the Medical Outcomes
      Study Short Form 12-Item Health Survey (SF-12) after stabilization of mental
      condition. Differences between individual antipsychotic medications were compared
      using anova and multinomial regression model. RESULTS: The results demonstrated
      significant differences between different antipsychotic medications in the mean
      of UKU neurological subscore, BARS total score, SOFAS score and SF-12 Mental
      Component Summary (MCS) score. Patients with haloperidol had higher mean UKU
      neurological subscore than patients with olanzapine or amisulpride. Risperidone
      was associated with higher mean BARS total score than olanzapine, amisulpride or
      sulpiride. Higher mean MCS was found in patients with amisulpride than patients
      with risperidone. CONCLUSIONS: The findings suggest that antipsychotics have
      differential associations with the quality of life and functioning in patients
      with first-episode psychosis. Future prospective study is warranted to
      investigate if patients with first-episode psychosis will benefit specific type
      of antipsychotics more than the others.

PMID- 25967147
TI  - Dual element ((15)N/(14)N, (13)C/(12)C) isotope analysis of glyphosate and AMPA
      by derivatization-gas chromatography isotope ratio mass spectrometry (GC/IRMS)
      combined with LC/IRMS.
AB  - To assess sources and degradation of the herbicide glyphosate [N
      (phosphonomethyl) glycine] and its metabolite AMPA (aminomethylphosphonic acid),
      concentration measurements are often inconclusive and even (13)C/(12)C analysis
      alone may give limited information. To advance isotope ratio analysis of an
      additional element, we present compound-specific (15)N/(14)N analysis of
      glyphosate and AMPA by a two step derivatization in combination with gas
      chromatography/isotope ratio mass spectrometry (GC/IRMS). The N-H group was
      derivatized with isopropyl chloroformate (iso-PCF), and remaining acidic groups
      were subsequently methylated with trimethylsilyldiazomethane (TMSD). Iso-PCF
      treatment at pH <10 gave too low (15)N/(14)N ratios indicating an incomplete
      derivatization; in contrast, too high (15)N/(14)N ratios at pH >10 indicated
      decomposition of the derivative. At pH 10, and with an excess of iso-PCF by 10
      24, greatest yields and accurate (15)N/(14)N ratios were obtained (deviation from
      elemental analyzer-IRMS: -0.2 +/- 0.9% for glyphosate; -0.4 +/- 0.7% for AMPA).
      Limits for accurate delta(15)N analysis of glyphosate and AMPA were 150 and 250
      ng injected, respectively. A combination of delta(15)N and delta(13)C analysis by
      liquid chromatography/isotope ratio mass spectrometry (LC/IRMS) (1) enabled an
      improved distinction of commercial glyphosate products and (2) showed that
      glyphosate isotope values during degradation by MnO2 clearly fell outside the
      commercial product range. This highlights the potential of combined carbon and
      nitrogen isotopes analysis to trace sources and degradation of glyphosate.

PMID- 25967148
TI  - Sample preparation strategies for improving the identification of membrane
      proteins by mass spectrometry.
AB  - Despite enormous advances in the mass spectrometry and proteomics fields during
      the last two decades, the analysis of membrane proteins still remains a challenge
      for the proteomic community. Membrane proteins play a wide number of key roles in
      several cellular events, making them relevant target molecules to study in a
      significant variety of investigations (e.g., cellular signaling, immune
      surveillance, drug targets, vaccine candidates, etc.). Here, we critically review
      the several attempts that have been carried out on the different steps of the
      sample preparation procedure to improve and modify existing conventional
      proteomic strategies in order to make them suitable for the study of membrane
      proteins. We also revise novel techniques that have been designed to tackle the
      difficult but relevant task of identifying and characterizing membrane proteins. 

PMID- 25967149
TI  - A candidate reference measurement procedure for quantifying serum concentrations
      of 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2 using isotope-dilution liquid
      chromatography-tandem mass spectrometry.
AB  - The inaccuracy of routine serum 25-hydroxyvitamin D measurements hampers the
      interpretation of data in patient care and public health research. We developed
      and validated a candidate reference measurement procedure (RMP) for highly
      accurate quantitation of two clinically important 25-hydroxyvitamin D metabolites
      in serum, 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3].
      The two compounds of interest together with spiked deuterium-labeled internal
      standards [d 3-25(OH)D2 and d 6-25(OH)D3] were extracted from serum via liquid
      liquid extraction. The featured isotope-dilution LC-MS/MS method used reversed
      phase chromatography and atmospheric pressure chemical ionization in positive ion
      mode. A pentafluorophenylpropyl-packed UHPLC column together with isocratic
      elution allowed for complete baseline resolution of 25(OH)D2 and 25(OH)D3 from
      their structural C-3 isomers within 12 min. We evaluated method trueness,
      precision, potential interferences, matrix effects, limits of quantitation, and
      measurement uncertainty. Calibration materials were, or were traceable to, NIST
      Standard Reference Materials 2972. Within-day and total imprecision (CV) averaged
      1.9 and 2.0% for 25(OH)D3, respectively, and 2.4 and 3.5% for 25(OH)D2,
      respectively. Mean trueness was 100.3% for 25(OH)D3 and 25(OH)D2. The limits of
      quantitation/limits of detection were 4.61/1.38 nmol/L for 25(OH)D3 and 1.46/0.13
      nmol/L for 25(OH)D2. When we compared our RMP results to an established RMP using
      40 serum samples, we found a nonsignificant mean bias of 0.2% for total 25(OH)D.
      This candidate RMP for 25(OH)D metabolites meets predefined method performance
      specifications (<=5% total CV and <=1.7% bias) and provides sufficient sample
      throughput to meet the needs of the Centers for Disease Control and Prevention
      Vitamin D Standardization Certification Program. Graphical abstract Bias
      assessment using NIST standard reference materials. Legend CDC mean mass
      fractions (ng/g) +/- U 95 (6 replicates per mean). NIST-certified mass fractions
      (ng/g) +/- U 95 from the Certificates of Analysis.

PMID- 25967150
TI  - Raman spectroscopic characterisation of resin-infiltrated hypomineralised enamel.
AB  - Raman spectroscopy was used to investigate how the effect of pre-treatment
      protocols, with combinations of hydrochloric acid (HCl), sodium hypochlorite
      (NaOCl) and hydrogen peroxide (H2O2), for molar-incisor hypo-mineralisation (MIH)
      altered the penetration depth of polymer infiltrants (ICON, DMG, Hamburg,
      Germany). Furthermore, the effect on the structure of the MIH portions of the
      teeth with treatment is examined using multivariate analysis of spectra. It was
      found that pre-treatment protocols improved penetration depths. The structure of
      the MIH portion post-treatment appeared much closer to that of normal enamel
      suggesting a diminution of protein in the MIH region with treatment. 

PMID- 25967151
TI  - MTB-DR-RIF 9G membrane: a platform for multiplex SNP detection of multidrug
      resistant TB.
AB  - The MTB-DR-RIF 9G membrane can detect by detecting multiple mutations in multiple
      codons. The MTB-DR-RIF 9G membrane possesses clinical applicability in point-of
      care settings for the following reasons: (i) 100% similar results with that of
      the sequencing analysis for clinical samples, (ii) discrimination of the multiple
      mutations in multiple codons, (iii) a specific/non-specific hybridization ratio
      higher than 350:1, and (iv) the sensitivity was found to be 1-10 copies/test for
      detection and discrimination of the wild and mutant TB strains. Graphical
      abstract Schematic illustration of the effect of controller DNA on the
      hybridization of the immobilized probes (corresponding to the wild TB strain)
      with the PCR product of (a) wild TB strain and (b) mutant TB strain.

PMID- 25967152
TI  - Direct injection of tissue extracts in liquid chromatography/tandem mass
      spectrometry for the determination of pharmaceuticals and other contaminants of
      emerging concern in mollusks.
AB  - In the present study, a straightforward approach was validated for the analysis
      of pharmaceutically active compounds and endocrine-disrupting chemicals in the
      mollusk tissues, with a focus on two species commonly consumed in Southeast Asia
      (green mussels: Perna viridis; lokan clams: Polymesoda expansa). This approach
      relied on a simple solvent extraction (shaker table) followed by direct injection
      in liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). This
      "cleanup-free" approach was made possible by the use of isotopically labeled
      surrogates (to correct for matrix effects) and a post-column switch on the LC
      MS/MS system (to remove potential interfering material). Altogether, relative
      recoveries were satisfactory for 36 out of 44 compounds (26-163% range) and
      excellent for 27 out of 44 compounds (79-107% range). Method detection limits
      (MDLs) were usually expressed in the nanogram per gram wet weight (ww) range and
      below. The method was successfully applied to 16 batches of green mussel samples
      collected in Singapore coastal waters. Trace levels of six compounds were
      detected in mussel tissues: caffeine (0.22-1.55 ng g(-1) ww), carbamazepine (<MDL
      0.10 ng g(-1) ww), diltiazem (<MDL-0.13 ng g(-1) ww), diphenhydramine (<MDL-1.31
      ng g(-1) ww), atrazine (<MDL-0.19 ng g(-1) ww), and bisphenol A (<MDL-7.6 ng g(
      1) ww). The present method offers the perspective of high sample throughput,
      allowing for intensive monitoring programs and detailed exposure assessments.

PMID- 25967153
TI  - Cell proliferation on modified DLC thin films prepared by plasma enhanced
      chemical vapor deposition.
AB  - Recently, diamondlike carbon (DLC) thin films have gained interest for biological
      applications, such as hip and dental prostheses or heart valves and coronary
      stents, thanks to their high strength and stability. However, the
      biocompatibility of the DLC is still questionable due to its low wettability and
      possible mechanical failure (delamination). In this work, DLC:N:O and DLC: SiOx
      thin films were comparatively investigated with respect to cell proliferation.
      Thin DLC films with an addition of N, O, and Si were prepared by plasma enhanced
      CVD from mixtures of methane, hydrogen, and hexamethyldisiloxane. The films were
      optically characterized by infrared spectroscopy and ellipsometry in UV-visible
      spectrum. The thickness and the optical properties were obtained from the
      ellipsometric measurements. Atomic composition of the films was determined by
      Rutherford backscattering spectroscopy combined with elastic recoil detection
      analysis and by x-ray photoelectron spectroscopy. The mechanical properties of
      the films were studied by depth sensing indentation technique. The number of
      cells that proliferate on the surface of the prepared DLC films and on control
      culture dishes were compared and correlated with the properties of as-deposited
      and aged films. The authors found that the level of cell proliferation on the
      coated dishes was high, comparable to the untreated (control) samples. The
      prepared DLC films were stable and no decrease of the biocompatibility was
      observed for the samples aged at ambient conditions. 

PMID- 25967154
TI  - Impact of left ventricular conduction defect with or without need for permanent
      right ventricular pacing on functional and clinical recovery after TAVR.
AB  - BACKGROUND: Left ventricular conduction disturbances (VCD) with or without need
      for pacemaker (PM) implantation are common after transcatheter aortic valve
      replacement (TAVR). Its effect on patients' functional recovery after TAVR is
      unclear. METHODS AND RESULTS: 212 patients (Age 80.8 +/- 6.4 years, logEuroscore
      28.95 +/- 17.37 %) underwent TAVR with the self-expanding CoreValve prosthesis
      and completed 9-month follow-up (FU). After TAVR 125 (59 %) patients were
      diagnosed with VCD. This group consists of 41 (19 %) patients with a new PM after
      TAVR, 33 (16 %) patients with PM prior TAVR and markedly increased ventricular
      stimulation rate, 48 (23 %) patients with new LBBB post-TAVR and three (1 %)
      patients with LBBB prior TAVR. After FU, the presence of VCD alone was associated
      with worse recovery of left ventricular ejection fraction (LVEF) (VCD:
      LVEFbaseline 51.7 +/- 18.2 %, LVEFFU 53.9 +/- 13.0 %; p = 0.8; noVCD:
      LVEFbaseline 53.8 +/- 12.9 %, LVEFFU 63.4 +/- 10.1 %; p < 0.01) but had no impact
      on functional outcomes after TAVR (p > 0.05). Especially patients with VCD caused
      by permanent RV pacing showed worse functional outcomes presenting with higher
      functional NYHA classes (p < 0.05), and higher NT-proBNP levels (p < 0.05). 20.4
      % of patients with need for PM after TAVR remained in NYHA class >=3, as compared
      to 5 % of patients without PM (VCD but no PM: 4.7 %, p < 0.001; noVCD: 5.3 %, p <
      0.001). VCD with or without need for PM had no impact on survival after FU.
      CONCLUSION: The occurrence of VCD after TAVR is common and associated with
      unfavorable left ventricular functional recovery. However, only the combination
      of VCD with permanent right ventricular pacing has adverse impact on heart
      failure-related symptoms after TAVR.

PMID- 25967156
TI  - Mammalian herbivores confer resilience of Arctic shrub-dominated ecosystems to
      changing climate.
AB  - Climate change is resulting in a rapid expansion of shrubs in the Arctic. This
      expansion has been shown to be reinforced by positive feedbacks, and it could
      thus set the ecosystem on a trajectory toward an alternate, more productive
      regime. Herbivores, on the other hand, are known to counteract the effects of
      simultaneous climate warming on shrub biomass. However, little is known about the
      impact of herbivores on resilience of these ecosystems, that is, the capacity of
      a system to absorb disturbance and still remain in the same regime, retaining the
      same function, structure, and feedbacks. Here, we investigated how herbivores
      affect resilience of shrub-dominated systems to warming by studying the change of
      shrub biomass after a cessation of long-term experimental warming in a forest
      tundra ecotone. As predicted, warming increased the biomass of shrubs, and in the
      absence of herbivores, shrub biomass in tundra continued to increase 4 years
      after cessation of the artificial warming, indicating that positive effects of
      warming on plant growth may persist even over a subsequent colder period.
      Herbivores contributed to the resilience of these systems by returning them back
      to the original low-biomass regime in both forest and tundra habitats. These
      results support the prediction that higher shrub biomass triggers positive
      feedbacks on soil processes and microclimate, which enable maintaining the rapid
      shrub growth even in colder climates. Furthermore, the results show that in our
      system, herbivores facilitate the resilience of shrub-dominated ecosystems to
      climate warming.

PMID- 25967157
TI  - 20th meeting of the European society of neurosonology and cerebral hemodynamics.
      Zadar, croatia, may 7-11, 2015: abstracts.

PMID- 25967155
TI  - Association between muscular strength and inflammatory markers among elderly
      persons with cardiac disease: results from the KORA-Age study.
AB  - Little is known about the association between muscle strength and inflammation in
      diseased individuals and particularly in cardiac patients. Thus, our purpose was
      to examine the association of muscular strength with the inflammatory status in
      older adults with and without cardiac disease. The cross-sectional analysis was
      based on 1079 adults aged 65-94 years, who participated in the KORA-Age study.
      Participants underwent an interview and extensive physical examinations including
      anthropometric measurements, registration of diseases and drug intake,
      determination of health-related behaviors, collection of blood samples for
      measurements of interleukin-6 and hs-CRP and muscle strength measurement using
      hand-grip dynamometry. Cardiac patients (n = 323) had higher levels of IL-6 and
      poorer muscle strength compared with older adults without cardiac disease. Among
      persons with cardiac diseases, muscle strength in the lower tertile compared to
      the upper tertile was significantly associated with increased odds of having
      elevated IL-6 levels (OR 3.53, 95 % CI 1.18-10.50, p = 0.024) after controlling
      for age, gender, body fat, alcohol intake, smoking status, diseases, medications
      and physical activity, whereas the association between muscle strength and hs-CRP
      remained borderline significant (OR 2.80, 95 % CI 0.85-9.24, p = 0.092). The same
      trends, with slightly lower odds ratios, were also observed in older adults
      without cardiac disease. Lower levels of muscular strength are associated with
      higher concentrations of IL-6 and hs-CRP in elderly individuals with and without
      cardiac disease suggesting a significant contribution of the muscular system in
      reducing low-grade inflammation that accompanies cardiac disease and aging. 

PMID- 25967159
TI  - Plasmonic bandpass filter based on graphene nanoribbon.
AB  - A plasmonic bandpass filter based on graphene is proposed and numerically
      investigated using the finite-difference time-domain method. The proposed filter
      has a very simple structure, including two graphene nanoribbon waveguides
      laterally coupled to a graphene ribbon resonator. The transmission efficiency can
      be tuned by altering the coupling distance between the ribbons. At the same time,
      the variation of the transmission spectra is investigated by tuning the size of
      the graphene resonant ribbon. Notably, due to the unique electronic tunability of
      graphene, the transmission spectra can be freely tuned in a broad frequency range
      by choosing the chemical potential, which exhibits more flexible tunability than
      that used in conventional metallic devices. Attributed to the standing wave
      distribution of different modes excited in the graphene resonant ribbon, the
      proposed filter can be used for the plasmonic device with the capability of band
      selection or power splitting by locating the output waveguide ports in the
      suitable positions. 

PMID- 25967160
TI  - Depth plane adaptive integral imaging using a varifocal liquid lens array.
AB  - This paper proposes an enhanced integral imaging system with an electrically
      controllable image plane to address the issue of the limited depth problem in
      integral imaging. For implementation of the variable image plane, a varifocal
      liquid lens array and driving device are adopted instead of an ordinary solid
      lens array. The position of the central depth plane is varied by adjusting the
      focal length of the lens array. The proposed system enables matching between the
      object position and depth plane electrically, and thus an object moving from 5.15
      to 11.72 cm is clearly displayed with this method.

PMID- 25967158
TI  - Progesterone-mediated effects on gene expression and oocyte-cumulus complex
      transport in the mouse fallopian tube.
AB  - BACKGROUND: The fallopian tube transports the gametes to the fertilization site
      and delivers the embryo to the uterus at the optimal time for implantation.
      Progesterone and the classical progesterone receptor are involved in regulating
      both tubal ciliary beating and muscular contractions, likely via both genomic and
      non-genomic actions. METHODS: To provide more details of the underlying
      mechanisms, we investigated the effect of progesterone on gene expression in mice
      fallopian tubes in vitro at 20 min, 2 h and 8 h post progesterone treatment using
      microarray and/or quantitative PCR. In parallel, oocyte cumulus complex transport
      was investigated in ovulating mice that were injected with one of the
      progesterone receptor antagonists, Org 31710 or CDB2194. RESULTS: Microarray
      analyses did not reveal any apparently regulated genes 20 min after progesterone
      treatment, consistent with the proposed non-genomic action of progesterone
      controlling ciliary beating. After 2 h, 11 genes were identified as up-regulated.
      Analyses using quantitative PCR at 2 h and 8 h showed a consistent up-regulation
      of endothelin1 and a down-regulation of its receptor Endothelin receptor A by
      progesterone. We also confirmed that treatment with progesterone receptor
      antagonists before ovulation accelerates the transport of the oocyte cumulus
      complex. CONCLUSIONS: This is the first study showing that progesterone regulates
      the expression of endothelin1 and endothelin receptor A in the fallopian tube.
      Together with previous studies of the effects of endothelin on muscular
      contractions in the fallopian tube, the results from this study suggest that
      endothelin is a mediator of the progesterone-controlled effects on muscular
      contraction and eventually gamete transport in the fallopian tube.

PMID- 25967161
TI  - Photoemission performance of thin graded structure AlGaN photocathode.
AB  - In order to research a high-efficiency AlGaN photocathode, the AlGaN
      photocathodes with varied Al composition (0.68 and 0.4) and uniform Al
      composition (0.24) were grown. The photocathodes were activated by Cs adsorption
      and received their spectral response via multi-information system. Results show
      that the absorption rate of the AlGaN photocathode with varied Al composition is
      half of the AlGaN photocathode with uniform Al composition, but the quantum
      efficiency of the photocathode with varied Al composition is approximately 29%
      higher than that of the photocathode with uniform Al composition. The built-in
      field within the emission layer of the AlGaN photocathode with varied Al
      composition is much higher than that of the photocathode with uniform Al
      composition, which is the main factor that promotes the photoelectron movement
      toward the photocathode surface and improves photoemission performance of the
      AlGaN photocathode. 

PMID- 25967162
TI  - Single-shot Z(eff) dense plasma diagnostic through simultaneous refraction and
      attenuation measurements with a Talbot-Lau x-ray moire deflectometer.
AB  - The Talbot-Lau x-ray moire deflectometer is a powerful plasma diagnostic capable
      of delivering simultaneous refraction and attenuation information through the
      accurate detection of x-ray phase shift and intensity. The diagnostic can provide
      the index of refraction n=1-delta+ibeta of an object (dense plasma, for example)
      placed in the x-ray beam by independently measuring both delta and beta, which
      are directly related to the electron density n(e) and the attenuation coefficient
      MU, respectively. Since delta and beta depend on the effective atomic number
      Z(eff), a map can be obtained from the ratio between phase and absorption images
      acquired in a single shot. The Talbot-Lau x-ray moire deflectometer and its
      corresponding data acquisition and processing are briefly described to illustrate
      how the above is achieved; Z(eff) values of test objects within the 4-12 range
      were obtained experimentally through simultaneous refraction and attenuation
      measurements. We show that Z(eff) mapping of objects does not require previous
      knowledge of sample length or shape. The determination of Z(eff) from refraction
      and attenuation measurements with moire deflectometry could be of high interest
      to various domains of high energy density research, such as shocked materials and
      inertial confinement fusion experiments, as well as material science and
      nondestructive testing.

PMID- 25967163
TI  - Analytical approach of ordinary frozen waves for optical trapping and
      micromanipulation.
AB  - The optical properties of frozen waves (FWs) are theoretically and numerically
      investigated using the generalized Lorenz-Mie theory (GLMT) together with
      integral localized approximation. These waves are constructed from a suitable
      superposition of equal-frequency ordinary Bessel beams and are capable of
      providing almost any desired longitudinal intensity profile along their optical
      axis, thus being of potential interest in applications in which intensity
      localization may be used advantageously, such as in optical trapping and
      micromanipulation systems. In addition, because FWs are composed of
      nondiffracting beams, they are also capable of overcoming the diffraction effects
      for longer distances when compared to conventional (ordinary) beams, e.g.,
      Gaussian beams. Expressions for the beam-shape coefficients of FWs are provided,
      and the GLMT is used to reconstruct their intensity profiles and to predict their
      optical properties for possible biomedical optics purposes. 

PMID- 25967164
TI  - Broadband and tunable optical parametric generator for remote detection of gas
      molecules in the short and mid-infrared.
AB  - The development of a novel broadband and tunable optical parametric generator
      (OPG) is presented. The OPG properties are studied numerically and experimentally
      in order to optimize the generator's use in a broadband spectroscopic LIDAR
      operating in the short and mid-infrared. This paper discusses trade-offs to be
      made on the properties of the pump, crystal, and seeding signal in order to
      optimize the pulse spectral density and divergence while enabling energy scaling.
      A seed with a large spectral bandwidth is shown to enhance the pulse-to-pulse
      stability and optimize the pulse spectral density. A numerical model shows
      excellent agreement with output power measurements; the model predicts that a
      pump having a large number of longitudinal modes improves conversion efficiency
      and pulse stability. 

PMID- 25967165
TI  - Investigation of optical bistability in a double In(x)Ga(1-x)N/GaN quantum-dot
      nanostructure via inter-dot tunneling effect.
AB  - In this paper, our aim is to control optical bistability (OB) and optical
      multistability (OM) in a five-level system designed in a double quantum dot (QD)
      nanostructure. In a realistic example, this atomic system is created in two
      semiconductor QDs (In(x)Ga(1-x)N/GaN), owning transfer of carriers via tunneling
      effect. OB behavior is controlled not only by the inter-dot tunneling effect but
      also by variation of probe detuning and intensity of the control field. It is
      demonstrated that voltage-controlled detuning can significantly affect the
      behavior of OB and OM; therefore, the OM converts to OB by probe detuning and
      intensity of the control field.

PMID- 25967166
TI  - Weak-signal iterative holography.
AB  - An iterative holographic table-top experiment is presented, where a recorded
      hologram is used to re-illuminate the initial target. With this beam shaping
      setup, more light is directed to the target for each iteration until a
      convergence limit is met. We experimentally examine convergence properties of
      this iterative hologram reconstruction approach for weak object signals and
      compare with theory. 

PMID- 25967167
TI  - Intensity-modulated relative humidity sensing with polyvinyl alcohol coating and
      optical fiber gratings.
AB  - A relative humidity (RH) sensor in reflection mode is proposed and experimentally
      demonstrated by using a polyvinyl alcohol (PVA)-coated tilted-fiber Bragg grating
      (TFBG) cascaded by a reflection-band-matched chirped-fiber Bragg grating (CFBG).
      The sensing principle is based on the RH-dependent refractive index of the PVA
      coating, which modulates the transmission function of the TFBG. The CFBG is
      properly designed to reflect a broadband of light spectrally suited at the
      cladding mode resonance region of the TFBG, thus the reflected optical signal
      passes through and is modulated by the TFBG again. As a result, RH measurements
      with enhanced sensitivity of ~1.80  MUW/%RH are realized and demodulated in the
      range from 20% RH to 85% RH.

PMID- 25967168
TI  - Dichroic directional excitation of surface plasmon based on an integer
      programming model.
AB  - A silver film perforated with two subwavelength uniform slits is proposed for
      dichroic directional excitation of surface plasmon polaritons (SPPs). Under
      backside oblique illumination, the SPPs for two work wavelengths can propagate
      along the two opposite directions or in the same direction. Based on SPP
      interference, an integer-programming model is established for dichroic
      directional excitation of SPPs. The branch and bound method is introduced to find
      the optimal solutions for the integer-programming model, and therefore, the
      parameters of the structure and illumination angles can be obtained. The field
      distribution of the structure is investigated by using the finite-difference time
      domain method (FDTD) to verify our design. Our theoretical model can achieve
      dichroic directional excitation of SPPs, simultaneously. 

PMID- 25967169
TI  - Inner scale effect on scintillation index of flat-topped beam in non-Kolmogorov
      weak turbulence.
AB  - A simpler generalized expression of irradiance fluctuation for flat-topped beams
      is presented based on the Born and Rytov perturbation methods. The theoretical
      expression of the on-axis scintillation index in non-Kolmogorov weak atmospheric
      optics links is developed using the generalized von Karman spectrum model, and
      using the equivalent structure constant that is different for all power-law
      exponents. The effect of the inner scale on the on-axis scintillation index is
      examined comprehensively. It is observed that flat-topped beams happen to possess
      smaller scintillation indices at larger inner scale. The effects of the power
      law, flat-topped order, source size of the fundamental Gaussian beam, propagation
      distance, and wavelength are also analyzed. 

PMID- 25967170
TI  - Ultimate sensing resolution of water temperature by remote Raman spectroscopy.
AB  - The limit of sensing resolution of water temperature by remote Raman spectroscopy
      was investigated experimentally. A remote Raman spectrometer, which employed a
      telescope of 20 cm in pupil size and the second harmonic generation (SHG) of a Q
      switched Nd:YAG laser, was used for the measurement. By analyzing the broad O-H
      stretching Raman band located near 3500  cm-1, a parameter which is in second
      order polynomial relation with water temperature from 13 degrees C to 50 degrees
      C could be obtained. The resolution of our remote Raman temperature sensor was
      better than +/-0.2 degrees C with measurement time shorter than 10 s. The
      influence of the Raman signal's signal-to-noise ratio on the resolution and
      salinity effect on the accuracy of temperature sensing were also investigated.

PMID- 25967171
TI  - Photonic crystal fiber interferometric pH sensor based on polyvinyl
      alcohol/polyacrylic acid hydrogel coating.
AB  - We present a simple photonic crystal fiber interferometer (PCFI) that operates in
      reflection mode for pH measurement. The sensor is made by coating polyvinyl
      alcohol/polyacrylic acid (PVA/PAA) hydrogel onto the surface of the PCFI,
      constructed by splicing a stub of PCF at the distal end of a single-mode fiber
      with its free end airhole collapsed. The experimental results demonstrate a high
      average sensitivity of 0.9 nm/pH unit for the 11 wt.% PVA/PAA coated sensor in
      the pH range from 2.5 to 6.5. The sensor also displays high repeatability and
      stability and low cross-sensitivity to temperature. Fast, reversible rise and
      fall times of 12 s and 18 s, respectively, are achieved for the sensor time
      response.

PMID- 25967172
TI  - Titanium dioxide slot waveguides for visible wavelengths.
AB  - We present the first, to our knowledge, experimental demonstration of a titanium
      dioxide slot waveguide operating in the visible range of light. Ring resonators
      based on slot waveguides were designed, fabricated, and characterized for
      lambda?650  nm. The fabrication method includes atomic layer deposition, electron
      beam lithography, and reactive ion etching. The required narrow slot widths of a
      few tens of nanometers were achieved by using a conformal atomic layer re-coating
      technique. This unique feature-size-reduction technique was applied after the
      final etching step.

PMID- 25967173
TI  - Deformation verification and surface improvement of active stressed lap for 4  m
      class primary mirror fabrication.
AB  - The surface shape accuracy of the active stressed lap impacts the performance of
      grinding and polishing in the fabrication of large mirrors. We introduce a model
      of active stressed lap for the fabrication of a 4 m f/1.5 mirror based on finite
      element analysis (FEA), and the lap surface accuracy achieves RMS<1.8  MUm in the
      FEA method. Using the lap surface measurement system, experimental verification
      is put forward, and the RMS of the measured lap surface is within 2 MUm in
      practice. A general improvement in lap surface accuracy using the Zernike
      polynomial is shown. After compensating the calculation errors, the lap surface
      accuracy is improved by 8%-23%, and achieves RMS<1.5  MUm, which is appropriate
      for practical grinding and polishing.

PMID- 25967174
TI  - Beam diffraction by a resistive half-plane.
AB  - The scattering of a Gaussian beam by a resistive half-screen is investigated. Far
      field approximation is used in evaluation of geometrical optics and diffracted
      waves. The uniform expression of the diffracted waves by the resistive half
      plane, which was found with the Sommerfeld-Maliuzhinets method, is obtained. The
      scattered fields for the case of the beam incidence are evaluated with the
      technique of a complex point source. The resultant wave expressions are examined
      numerically. 

PMID- 25967175
TI  - Electrowetting-actuated optical switch based on total internal reflection.
AB  - In this paper we demonstrate a liquid optical switch based on total internal
      reflection. Two indium tin oxide electrodes are fabricated on the bottom
      substrate. A conductive liquid (Liquid 1) is placed on one side of the chamber
      and surrounded by a density-matched silicone oil (Liquid 2). In initial state,
      when the light beam illuminates the interface of the two liquids, it just meets
      the conditions of total internal reflection. The light is totally reflected by
      Liquid 2, and the device shows light-off state. When we apply a voltage to the
      other side of the indium tin oxide electrode, Liquid 1 stretched towards this
      side of the substrate and the curvature of the liquid-liquid interface changes.
      The light beam is refracted by Liquid 1 and the device shows light-on state. So
      the device can achieve the functions of an optical switch. Because the light beam
      can be totally reflected by the liquid, the device can attain 100% light
      intensity attenuation. Our experiments show that the response time from light-on
      (off) to light-off (on) are 130 and 132 ms, respectively. The proposed optical
      switch has potential applications in variable optical attenuators, information
      displays, and light shutters. 

PMID- 25967176
TI  - Method of simultaneous measurement of two direction force and temperature using
      FBG sensor head.
AB  - This paper presents a method for measuring two components of bending force and
      temperature using one sensor head. Indirect inference based on the spectra of two
      fiber Bragg gratings (FBGs) placed on a cantilever beam is used. The method was
      developed during work on the inverse problem of determining a nonuniform stress
      distribution based on FBG spectra. A gradient in the FBG stress profile results
      in a characteristic shape of its reflective spectrum. The simultaneous
      measurements of force and temperature were possible through the use of an
      appropriate layout of the sensor head. The spectral characteristics of the
      sensor's gratings do not retain full symmetry, which is due to the geometry of
      the sensor's head and the related difference in the distribution of the axial
      stress of the gratings. In the proposed approach, the change in width of the sum
      of the normalized transmission spectra was used to determine the value of the
      applied force. In the presented method, an increase in the sensitivity of this
      change to the force is obtained relative to the other known systems. A change in
      the spectral width was observed for an increase in bending forces from 0 to 150
      N. The sensitivity coefficient of the spectral width to force, defined as the
      ratio of the change of the spectral half-width to the change in force was 2.6e-3 
      nm/N for the first grating and 1.2e-3  nm/N for the second grating. However, the
      sensitivity of the whole sensor system was 5.8e-3  nm/N, which is greater than
      the sum of the sensitivities of the individual gratings. For the purpose of this
      work, a station with a thermal chamber has been designed with a bracket on which
      fiber optic transducers have been mounted for use in further measurements. The
      sensor head in this experiment is considered to be a universal device with
      potential applications in other types of optical sensors, and it can be treated
      as a module for development through its multiplication on a single optical fiber.

PMID- 25967177
TI  - Diode-pumped passively dual-wavelength Q-switched Nd:GYSGG laser using graphene
      oxide as the saturable absorber.
AB  - The performance of a diode end-pumped passively Q-switched dual-wavelength
      Nd:GYSGG laser operating at 1057.28 and 1060.65 nm with graphene oxide as the
      saturable absorber was demonstrated. The maximum dual-wavelength average output
      power of 521 mW was achieved under the absorbed pump power of 5.4 W,
      corresponding to the optical-to-optical conversion and slope efficiency of 9.8%
      and 21%, respectively. The minimum pulse width was 115 ns with a pulse repetition
      rate of 338 kHz.

PMID- 25967178
TI  - Optical distortions in end-pumped zigzag slab lasers.
AB  - Ray tracing is performed to investigate the optical distortions in the end
      pumped, zigzag slab. Optical path differences caused by temperature, slab
      deformation, and stress birefringence are calculated under uniform pumping; the
      results show a steep edge in the width dimension and a thermal lens with an
      effective focal length as short as several meters in the thickness dimension.
      Dependence of depolarization on total internal reflection phase retardance as
      well as the slab's cut angle is studied by the Jones matrix technique; results
      show that although at the pumping power of 10 kW, the mean depolarization of the
      2.5  mm*30  mm*150.2  mm Nd:YAG slab is generally below 3%, and it increases
      rapidly with pumping power. Besides, for the 0 degrees - or 60 degrees -cut slab,
      an optimal phase retardance range of 5 degrees  to 13 degrees  exists, in which
      the depolarization loss can be lower than 0.5%. Finally, experiments on
      temperature and depolarization measurements verify the numerical results.

PMID- 25967179
TI  - Improved method for estimation of multiple parameters in self-mixing
      interferometry.
AB  - There are two categories of applications for self-mixing interference (SMI)-based
      sensing: (1) estimation of parameters associated with a semiconductor laser (SL)
      and (2) measurement of the metrological quantities of the external target. To
      achieve high resolution sensing, each category of applications requires knowledge
      from the other. This paper proposes an improved method that can simultaneously
      measure the parameters of an SL and the target movement in arbitrary form.
      Starting with the existing SMI model, we derive a new matrix equation for the
      measurement. The measurement matrix is built by employing all the available data
      samples obtained from an SMI signal. The total least squares estimation approach
      is used to estimate the parameters. The proposed method is verified by both
      simulations and experiments.

PMID- 25967180
TI  - Fano resonance by dipole-hexapole coupling in a chi-shaped plasmonic
      nanostructure.
AB  - We demonstrate that pronounced Fano resonance can be obtained by dipole-hexapole
      coupling in a chi-shaped plasmonic nanostructure. The confined local field in the
      vicinity of dipole-resonant nanorods excites and coherently couples to the
      hexapolar mode in the rod perpendicular to the polarization direction of the
      incident wave, leading to strong Fano resonance. By using the discrete dipole
      approximation, we numerically investigate the behavior of Fano resonance by
      dipole-hexapole coupling in the plasmonic nanostructure. We obtain the parameters
      relevant to Fano resonance by fitting the coupled oscillator model equation to
      the calculated extinction data and investigate their dependencies on the
      structural parameters. The results demonstrate the possibility of obtaining high
      contrast Fano resonance with narrow features by using this plasmonic
      nanostructure, which has potential applications for highly sensitive biological
      sensing, low-loss metamaterials, and others. 

PMID- 25967181
TI  - Beam shaping system based on a prism array for improving the throughput of a
      dispersive spectrometer.
AB  - A beam shaping system (BSS) for improving the throughput of a dispersive
      spectrometer is presented by employing two anamorphic lenses and a prism array to
      segment the beam. The BSS was designed based on the inverse method of beam
      shaping for laser diode bars and the means of an optical slicer. In an
      experiment, a BSS was set up so that the incident light of a neon lamp with a
      circular spot from an input fiber was transformed into an elliptical spot coupled
      into a slit of a spectrometer without a change of divergence. Spectral
      measurement results demonstrate that the throughput of the dispersive
      spectrometer was doubled without loss of spectral resolution. The BSS can be
      combined with the existing dispersive spectrometer to improve the luminous flux
      and signal-to-noise ratio. 

PMID- 25967182
TI  - Holographic fabrication of nanoantenna templates through a single reflective
      optical element.
AB  - In this paper, we present a single reflective optical element-based approach for
      the control of laser phase, polarization, and beam intensity for the holographic
      fabrication of nanoantenna templates. The single optical element can be designed
      and printed precisely by a 3D printer. The holographic fabrication is
      demonstrated in both negative and positive photoresists. The pattern fabricated
      is in agreement with simulations. The control of the nanogap size of nanoantennas
      is discussed in terms of the capabilities of the single-optical-element approach.

PMID- 25967183
TI  - Empirical correction of multifilter rotating shadowband radiometer (MFRSR)
      aerosol optical depths for the aerosol forward scattering and development of a
      long-term integrated MFRSR-Cimel dataset at Lampedusa.
AB  - Aerosol optical properties have been measured on the island of Lampedusa (35.5
      degrees N, 12.6 degrees E) with seven-band multifilter rotating shadowband
      radiometers (MFRSRs) and a CE 318 Cimel sunphotometer (part of the AERONET
      network) since 1999. Four different MFRSRs have operated since 1999. The Cimel
      sunphotometer has been operational for a short period in 2000 and in 2003-2006
      and 2010-present. Simultaneous determinations of the aerosol optical depth (AOD)
      from the two instruments were compared over a period of almost 4 years at several
      wavelengths between 415 and 870 nm. This is the first long-term comparison at a
      site strongly influenced by desert dust and marine aerosols and characterized by
      frequent cases of elevated AOD. The datasets show a good agreement, with MFRSR
      underestimating the Cimel AOD in cases with low Angstrom exponent; the
      underestimate decreases for increasing wavelength and increases with AOD. This
      underestimate is attributed to the effect of aerosol forward scattering on the
      relatively wide field of view of the MFRSR. An empirical correction of the MFRSR
      data was implemented. After correction, the mean bias (MB) between MFRSR and
      Cimel simultaneous AOD determinations is always smaller than 0.004, and the root
      mean square difference is <=0.031 at all wavelengths. The MB between MFRSR and
      Cimel monthly averages (for months with at least 20 days with AOD determinations)
      is 0.0052. Thus, by combining the MFRSR and Cimel observations, an integrated
      long-term series is obtained, covering the period 1999-present, with almost
      continuous measurements since early 2002. The long-term data show a small
      (nonstatistically significant) decreasing trend over the period 2002-2013, in
      agreement with independent observations in the Mediterranean. The integrated
      Lampedusa dataset will be used for aerosol climatological studies and for
      verification of satellite observations and model analyses.

PMID- 25967184
TI  - New coherent laser communication detection scheme based on channel-switching
      method.
AB  - A new coherent laser communication detection scheme based on the channel
      switching method is proposed. The detection front end of this scheme comprises a
      90 degrees  optical hybrid and two balanced photodetectors which outputs the in
      phase (I) channel and quadrature-phase (Q) channel signal current, respectively.
      With this method, the ultrahigh speed analog/digital transform of the signal of
      the I or Q channel is not required. The phase error between the signal and local
      lasers is obtained by simple analog circuit. Using the phase error signal, the
      signals of the I/Q channel are switched alternately. The principle of this
      detection scheme is presented. Moreover, the comparison of the sensitivity of
      this scheme with that of homodyne detection with an optical phase-locked loop is
      discussed. An experimental setup was constructed to verify the proposed detection
      scheme. The offline processing procedure and results are presented. This scheme
      could be realized through simple structure and has potential applications in cost
      effective high-speed laser communication. 

PMID- 25967185
TI  - Robust linear equation dwell time model compatible with large scale discrete
      surface error matrix.
AB  - The linear equation dwell time model can translate the 2D convolution process of
      material removal during subaperture polishing into a more intuitional expression,
      and may provide relatively fast and reliable results. However, the accurate
      solution of this ill-posed equation is not so easy, and its practicability for a
      large scale surface error matrix is still limited. This study first solves this
      ill-posed equation by Tikhonov regularization and the least square QR
      decomposition (LSQR) method, and automatically determines an optional interval
      and a typical value for the damped factor of regularization, which are dependent
      on the peak removal rate of tool influence functions. Then, a constrained LSQR
      method is presented to increase the robustness of the damped factor, which can
      provide more consistent dwell time maps than traditional LSQR. Finally, a matrix
      segmentation and stitching method is used to cope with large scale surface error
      matrices. Using these proposed methods, the linear equation model becomes more
      reliable and efficient in practical engineering. 

PMID- 25967186
TI  - Implementation of the photonic time-stretch concept using an incoherent pulsed
      light source.
AB  - We propose a new technique to realize photonic time stretching of radio-frequency
      (RF) signals by using a time-gated (pulsed) incoherent-light source. The proposed
      system provides similar performance specifications (stretch factor, temporal
      aperture, and resolution) to those of a conventional coherent system but using a
      temporal gating process that is significantly longer than the transform-limited
      pulse duration of the equivalent coherent configuration. We experimentally
      demonstrate temporal magnification and compression of high-speed RF signals, with
      time-stretch factors ranging from 0.65 to 8.66, using a broadband (11.6 nm)
      incoherent-light source temporally gated over ~163  ps. In one of the reported
      experiments, we achieve a resolution of ~67.5  ps over a temporal aperture of ~23
      ns, representing a time-bandwidth product of >340. 

PMID- 25967187
TI  - Estimation of excited-state absorption and photobleaching in Fe2+-doped lithium
      sodium silicate glass under exposure to high-power nanosecond laser pulses.
AB  - Fe-doped lithium sodium silicate glasses codoped with Sn and C to promote the
      Fe2+ redox state are investigated under simultaneous excitation at the first and
      third harmonics of a nanosecond Nd:YAG laser. The aim is to evaluate critical
      parameters associated with the potential use of this material as an optical
      filter that transmits the third harmonic but blocks the fundamental frequency.
      Estimations of the excited-state absorption coefficient and photobleaching
      (reduction of absorption at the fundamental) are provided. The results provide
      insight on the design and expected operational parameters of this type of Fe
      doped materials.

PMID- 25967188
TI  - Concept of annular vector beam generation at terahertz wavelengths via a
      nonlinear parametric process.
AB  - In this paper, we describe our theoretical investigation and calculations for a
      terahertz (THz)-wave profile generated by difference frequency mixing (DFM) of
      focused, cylindrically symmetric, and polarized optical vector beams. Using
      vector diffraction theory, the second-order nonlinear polarization was estimated
      from the electric field components of the optical pump beams penetrating
      uniaxial, birefringent nonlinear optics (NLO) crystals, GaSe and CdSe. The
      approximate beam patterns of the THz waves were simulated using DFM formulation.
      The intensity patterns of the THz waves for GaSe and CdSe showed sixfold symmetry
      and cylindrical symmetry, respectively, based on the nonlinear susceptibility
      tensor of the crystals. As the phase-matching angle theta(PM) was constant with
      respect to the c axis of the NLO crystals, an annular vector beam with a narrow
      width was expected.

PMID- 25967189
TI  - Mid-infrared Mueller ellipsometer with pseudo-achromatic optical elements.
AB  - The purpose of this article is to present a new broadband Mueller ellipsometer
      designed to work in the mid-infrared range, from 3 to 14 MUm. The Mueller
      ellipsometer, which can be mounted in reflection or in transmission
      configuration, consists of a polarization state generator (PSG), a sample holder,
      and a polarization state analyzer (PSA). The PSG consists of one linear polarizer
      and a retarder sequentially rotated to generate a set of four optimal
      polarization states. The retarder consists of a biprism made of two identical
      Fresnel rhombs disposed symmetrically and joined by an optical contact, giving
      the ensemble a "V" shape. Retardation is induced by the four total internal
      reflections that the beam undergoes when it propagates through the biprism. Total
      internal reflection allows the generation of a quasi-achromatic retardation. The
      PSA is identical to the PSG, but with its optical elements mounted in reverse
      order. After a measurement run, the instrument yields a set of sixteen
      independent values, which is the minimum amount of data required to calculate the
      Mueller matrix of the sample. The design of the Mueller ellipsometer is based on
      the optimization of an objective criterion that allows for minimizing the
      propagation of errors from raw data to the Mueller matrix of the sample. The
      pseudo-achromatic optical elements ensure a homogeneous quality of the
      measurements for all wavelengths. The performance of the Mueller ellipsometer, in
      terms of precision and accuracy, is discussed and illustrated with a few
      examples.

PMID- 25967190
TI  - Highly birefringent photonic crystal fiber with ultra-flattened negative
      dispersion over S  +  C  +  L  +  U bands.
AB  - We present a new cladding design for photonic crystal fiber (PCF) on a decagonal
      structure to simultaneously achieve ultra-flattened large negative dispersion and
      ultrahigh birefringence. Numerical results confirm that the proposed PCF exhibits
      ultra-flattened large negative dispersion over the S+C+L+U wavelength bands and
      average dispersion of about -558.96  ps/nm/km with absolute dispersion variation
      of 9.7  ps/nm/km from 1460 to 1675 nm (215 nm bandwidth). Moreover, ultrahigh
      birefringence of 0.0299 is also achieved at a 1500 nm wavelength.

PMID- 25967191
TI  - Lossless propagation in metal-semiconductor-metal plasmonic waveguides using
      quantum dot active medium.
AB  - In this paper, we analyze and simulate the lossless propagation of lightwaves in
      the active metal-semiconductor-metal plasmonic waveguides (MSMPWs) at the
      wavelength range of 1540-1560 nm using a quantum dot (QD) active medium. The
      Maxwell's equations are solved in the waveguide, and the required gains for
      achieving lossless propagation are derived. On the other hand, the rate equations
      in quantum dot active regions are solved by using the Runge-Kutta method, and the
      achievable optical gain is derived. The analyses results show that the required
      optical gain for lossless propagation in MSMPWs is achievable using the QD active
      medium. Also, by adjusting the active medium parameters, the MSMPWs loss can be
      eliminated in a specific bandwidth, and the propagation length increases
      obviously.

PMID- 25967192
TI  - Imaging and image restoration of an on-axis three-mirror Cassegrain system with
      wavefront coding technology.
AB  - Wavefront coding (WFC) technology is adopted in the space optical system to
      resolve the problem of defocus caused by temperature difference or vibration of
      satellite motion. According to the theory of WFC, we calculate and optimize the
      phase mask parameter of the cubic phase mask plate, which is used in an on-axis
      three-mirror Cassegrain (TMC) telescope system. The simulation analysis and the
      experimental results indicate that the defocused modulation transfer function
      curves and the corresponding blurred images have a perfect consistency in the
      range of 10 times the depth of focus (DOF) of the original TMC system. After
      digital image processing by a Wiener filter, the spatial resolution of the
      restored images is up to 57.14 line pairs/mm. The results demonstrate that the
      WFC technology in the TMC system has superior performance in extending the DOF
      and less sensitivity to defocus, which has great value in resolving the problem
      of defocus in the space optical system. 

PMID- 25967193
TI  - Polarization switching detection method using a ferroelectric liquid crystal for
      dichroic atomic vapor laser lock frequency stabilization techniques.
AB  - We present a concept of the polarization switching detection method implemented
      for frequency-stabilized lasers, called the polarization switching dichroic
      atomic vapor laser lock (PSDAVLL) technique. It is a combination of the well
      known dichroic atomic vapor laser lock method for laser frequency stabilization
      with a synchronous detection system based on the surface-stabilized ferroelectric
      liquid crystal (SSFLC).The SSFLC is a polarization switch and quarter wave-plate
      component. This technique provides a 9.6 dB better dynamic range ratio (DNR) than
      the well-known two-photodiode detection configuration known as the balanced
      polarimeter. This paper describes the proposed method used practically in the
      VCSEL laser frequency stabilization system. The applied PSDAVLL method has
      allowed us to obtain a frequency stability of 2.7*10-9 and a reproducibility of
      1.2*10-8, with a DNR of detected signals of around 81 dB. It has been shown that
      PSDAVLL might be successfully used as a method for spectra-stable laser sources.

PMID- 25967194
TI  - Large-scale three-dimensional measurement via combining 3D scanner and laser
      rangefinder.
AB  - This paper presents a three-dimensional (3D) measurement method of large-scale
      objects by integrating a 3D scanner and a laser rangefinder. The 3D scanner, used
      to perform partial section measurement, is fixed on a robotic arm which can slide
      on a guide rail. The laser rangefinder, used to compute poses of the 3D scanner,
      is rigidly connected to the 3D scanner. During large-scale measurement, after
      measuring a partial section, the 3D scanner is straightly moved forward along the
      guide rail to measure another section. Meanwhile, the poses of the 3D scanner are
      estimated according to its moved distance for different partial section
      alignments. The performance and effectiveness are evaluated by experiments. 

PMID- 25967195
TI  - Effect of scattering angle error on particle size determination by multiangle
      dynamic light scattering.
AB  - Dynamic light scattering (DLS) is a popular method of particle size measurement.
      Multiangle dynamic light scattering (MDLS) collects DLS data at multiple angles
      and analyzes the data simultaneously to improve the particle size measurement.
      Using data from several scattering angles admits the possibility of introducing
      noise caused by scattering angle error in the measurement, which may have an
      impact on the performance of the MDLS technique. We investigate the effect of
      scattering angle noise on recovered particle size distributions (PSDs) using
      simulated and measured MDLS data and various levels of angular noise. Our results
      show that, for unimodal PSDs, those with small particle sizes are more strongly
      affected by the noise than are medium and large particle size systems. For
      bimodal PSDs, those containing small-sized particles are also more affected by
      the noise than the systems of larger particles. Furthermore, broad PSDs are more
      vulnerable to angular noise than narrow PSDs. 

PMID- 25967196
TI  - Enhancement of the perceived image quality of a 2D/3D convertible directional
      backlight unit system using a double-slit barrier array and an active diffuser.
AB  - In this paper, a method to construct a directional-backlight unit system to
      separate the left-eye image and the right-eye image by adopting a double-slit
      barrier array is proposed to enhance the perceived quality of the realized 3D
      image. Additionally, the two-dimensional/three-dimensional convertible function
      is also realized by adopting an active diffuser to the spatial interlacing
      directional-backlight system. 

PMID- 25967198
TI  - Color-tunable light emitting diodes based on quantum dot suspension.
AB  - We propose a color-tunable light emitting diode (LED) consisting of a blue LED as
      the light source and quantum dot (QD) suspension as the color-conversion medium.
      The LED color temperature can be controlled by varying the liquid volume of each
      QD suspension with different photoluminescence colors. We simulate and optimize
      the light efficiency and color quality of the color-tunable LED and also
      fabricated a prototype to prove concept. The proposed color-tunable LED exhibits
      several advantages such as excellent color-rendering property, simple structure
      and driving mechanism, as well as high energy efficiency. Its potential
      applications include circadian rhythm regulation and healthy lighting. 

PMID- 25967197
TI  - Determination of aspheric vertex radius of curvature in non-null interferometry.
AB  - Traditional spherical radius of curvature interferometry is not valid for an
      aspheric vertex radius of curvature (VROC) due to the obstacle in identifying
      null positions (cat's eye or confocal position). Simultaneous optimization for
      multiconfiguration of an interferometer model is proposed to retrieve the actual
      aspheric VROC from its biased nominal value. This procedure works out the
      contradiction between VROC deviation and positioning error and even surface
      figure error, independent of absolute positioning by cat's eye or confocal
      position. In this method, the aspheric VROC and surface figure can be measured
      simultaneously, which facilitates the test process remarkably in practical
      optical shop testing. Furthermore, the parent VROC of a hollow aspheric (annular
      surface) also can be determined in this method. The performance of the proposed
      method is validated by experiments. 

PMID- 25967199
TI  - Broadband single-polarization single-mode photonic crystal fibers with three
      different background materials.
AB  - A modified structure of single-polarization single-mode (SPSM) photonic crystal
      fiber (PCF) with different background materials is presented and analyzed by
      using the full-vector finite-element method. Simulation results confirmed that
      the proposed PCF can realize low-loss SPSM on three wavebands with the same
      structure and different background materials. The wavebands are 1.46-1.60 MUm for
      silica-based fiber, 1.97-2.3 MUm for lead silicate glass fiber, and 3.16-3.58 MUm
      for chalcogenide glass fiber. For three PCFs with different background materials,
      only the slow-axis mode exists and the confinement loss is less than 100 dB/m in
      the SPSM wavebands.

PMID- 25967200
TI  - Holographic assessment of self-phase modulation and blooming in a thermal medium.
AB  - The use of a low-power laser beam to characterize self-phase modulation (SPM) and
      bubble formation during thermal blooming (TB), as well as manipulation of the
      bubbles, is reported. First, a low-power 633 nm laser beam is used to
      characterize the induced refractive index profile during SPM of a focused 514 nm
      pump beam in absorbing liquid media, e.g., a solution of red dye in isopropyl
      alcohol. The induced phase change is also characterized using digital holography
      via the 633 nm source as the probe and reference. During TB at higher pump
      powers, bubble formation occurs in the liquid. Using a modified setup, which
      minimizes the effects of gravity, buoyancy, and convection, stable bubbles are
      generated. These are characterized using in-line digital holography with the 633
      nm probe beam. It is shown that the bubble size depends on exposure time of the
      pump and that the bubble can be steered by moving a focused low-power laser beam.
      Finally, possible applications of these thermally generated bubbles are
      discussed.

PMID- 25967201
TI  - Radiation stability of visible and near-infrared optical and magneto-optical
      properties of terbium gallium garnet crystals.
AB  - Perspectives of terbium gallium garnet, Tb3Ga5O12 (TGG), for the use of radiation
      resistant high magnetic field sensing are studied. Long-term radiation stability
      of the TGG crystals was analyzed by comparing the optical and magneto-optical
      properties of a radiation-exposed TGG crystal (equivalent neutron dose 6.3*1013
      n/cm2) to the properties of TGG control samples. Simulations were also performed
      to predict radiation damage mechanisms in the TGG crystal. Radiation-induced
      increase in the absorbance at shorter wavelengths was observed as well as a
      reduction in the Faraday effect while no degradation of magneto-optical effect
      was observed when at wavelengths above 600 nm. This suggests that TGG crystal
      would be a good candidate for use in magneto-optical radiation-resistant magnetic
      field sensors.

PMID- 25967202
TI  - First approach to characterize tilts through multiple pistons in the classical
      Ronchi test.
AB  - In this work, it is shown how a tilt can be introduced into a segmented surface
      through several piston terms, by using the classical Ronchi test. We have
      developed tilt error simulations by adding multiple constant terms to each point
      on the sagitta surface of a segment using ray tracing. Thereby a comparison
      between simulated Ronchigrams for piston and tilt has been performed for two
      adjacent segments, so that it is possible to appreciate the tilt and piston
      effects on the shape of the patterns. As a result, we show the behavior of the
      central maximum of the fringes in the presence of tilt and/or piston.
      Additionally we present evidence of introducing tilting without changing the
      surface shape by adding multiple pistons, and a description of how to
      characterize both piston and tilt using the Ronchi test. 

PMID- 25967203
TI  - 1.5  kW ytterbium-doped single-transverse-mode, linearly polarized monolithic
      fiber master oscillator power amplifier.
AB  - A linearly polarized monolithic fiber laser based on a master oscillator power
      amplifier structure with a master oscillator and a one-stage power amplifier is
      reported. We design a homemade oscillator based on the theory that, in the coiled
      gain fiber, the higher modes and the polarized mode of the fundamental mode along
      the fast axis are suppressed effectively because of their obviously higher bend
      loss than that of the polarized mode of the fundamental mode along the slow axis.
      The oscillator operates at 1080 nm, launching a 30 W seed laser with a high
      polarization extinction ratio of 19 dB into the power amplifier via a mode field
      adapter. The power amplifier utilizes Yb-doped polarization-maintaining fiber of
      20/400  MUm, which produces nearly diffraction-limited output power of about 1.5
      kW with an optical-optical efficiency of 81.5% and a polarization extinction
      ratio of 13.8 dB. Both the M(x)2 factor and the M(y)2 factor of the collimated
      beam are measured to be about 1.2. The spectral width of the output power is
      broadened approximately linearly, and the full width at half maximum of the
      spectrum at the maximum output power is about 5.8 nm. It is known as the highest
      linearly polarized output power to the best of our knowledge.

PMID- 25967204
TI  - Small displacement measurements based on an angular-deviation amplifier and
      interferometric phase detection.
AB  - We propose a method for small displacement measurement based on the angle
      deviation to phase change transformation. The phase change of common-path
      heterodyne interferometry due to the angle deviation of incidence of a light at
      interfaces caused by the displacement is detected by a lock-in amplifier. To
      obtain more accurate results we used an angular amplifier to increase the angle
      deviation and utilized a surface plasmon resonance (SPR) sensor to enhance the
      performance of phase detection. When a translator moves one of two face-to-face
      plane mirrors at an end and then rotates it a small angle, a light is incident
      onto the mirrors and reflected N times. The outgoing light is also deflected N
      times of the angle and incident into a SPR sensor. Thus the phase shift due to
      the angle deviation is amplified N times. The accumulated phase shift is
      proportional to the amplified angle deviation and displacement. Therefore, the
      phase change is obtained and the displacement is measured. The amount of movement
      required can be as low as 0.13 MUm without an SPR sensor or 0.08 MUm with an SPR
      sensor. The maximum measurement range can reach 1000 MUm.

PMID- 25967205
TI  - High time-bandwidth product and high repetition rate period signal generation
      based on spectral hole burning crystal.
AB  - This paper proposes an approach for the generation of high time-bandwidth product
      (TBP) and high repetition rate pulse compression period signal. The complex
      spectral grating is created through a reference pulse and multiple programming
      pulses with different start frequencies. As the multiple probe chirped pulses
      with different start frequencies interact with the complex spectral gratings, a
      high TBP and repetition rate period signal is thus generated. This technique has
      the potential to generate a time-bandwidth product of 105 when the repetition
      rate reaches up to tens of GHz. At the end of this paper, two simulation results
      of pulse compression period signal with 4*105 TBP and 20 GHz repetition rate are
      presented.

PMID- 25967206
TI  - Object tracking based on incremental Bi-2DPCA learning with sparse structure.
AB  - In this paper, we propose a novel object tracking method that can work well in
      challenging scenarios such as appearance changes, motion blurs, and especially
      partial occlusions and noise. Our method applies bilateral two-dimensional
      principal component analysis (Bi-2DPCA) for efficient object modeling and real
      time computation requirement. An incremental Bi-2DPCA learning algorithm is
      proposed for characterizing the appearance changes of newly tracked objects.
      Also, to account for noise and occlusions, a sparse structure is introduced into
      our Bi-2DPCA object representation model. With this sparse structure, the
      appearance of an object can be represented by a linear combination of basis
      images and an additional noise image. The noise image, which indicates the
      location of noise and occlusions, can be used to effectively eliminate the
      influence caused by noise and occlusions and lead to a robust tracker. Instead of
      the reconstruction error commonly used in eigen-based tracking methods, a more
      accurate method is adopted for the computation of observation likelihood. The
      method is based on the energy distribution of coefficient matrix projected by Bi
      2DPCA. Experimental results on challenging image sequences demonstrate the
      effectiveness of the proposed tracking method. 

PMID- 25967207
TI  - Extractive FTIR spectroscopy with cryogen-free low-temperature inert
      preconcentration for autonomous measurements of atmospheric organics: 1:
      Instrument development and preliminary performance.
AB  - In collaboration with the Jefferson County Department of Health and the
      Environmental Protection Agency (EPA), the University of Alabama in Huntsville
      developed a novel sensor for detecting very low levels of volatile organic
      compounds (VOCs). This sensor uses a commercial Fourier-transform infrared (FTIR)
      spectrometer, a commercial long-path IR gas cell, a commercial acoustic Stirling
      cyrocooler, and a custom cryogen-free cryotrap to improve sensitivity in an
      autonomous system with on-board quality control and quality assurance. Laboratory
      and initial field results show this methodology is sensitive to and well-suited
      for a wide variety of VOC atmospheric research and monitoring applications,
      including EPA National Air Toxics Trends Stations and the National Core
      monitoring network. 

PMID- 25967208
TI  - Orthonormal polynomials for annular pupil including a cross-shaped obstruction.
AB  - By nonrecursive matrix method using the Zernike circle polynomials as the basis
      functions, we derived a set of polynomials up to fourth order which is
      approximately orthonormal for optical systems with an annular pupil having a
      cross-shaped obstruction. The performance of the polynomials is compared with the
      strictly orthonormal polynomials with some numerical examples. 

PMID- 25967209
TI  - Structural compensation enhancement method for nonuniform illumination images.
AB  - A structural compensation enhancement method is proposed to resolve the issue of
      nonuniform illumination image enhancement. A logarithmic histogram equalization
      transformation (LHET) is developed for improving the contrast of image and
      adjusting the luminance distribution. A structural map of illumination
      compensation is produced with a local ambient light estimation filter. The
      enhanced image is obtained by nonlinearly fusing the LHET result, reflection
      component, and structural map of illumination compensation. Unlike existing
      techniques, the proposed method has the ability of two-way adjustment for
      brightness. Furthermore, the proposed method can effectively enhance the
      nonuniform illumination images with a balance between visibility and naturalness.
      Extensive experimental comparisons with some state-of-the-art methods have shown
      the superior performance of the proposed method. 

PMID- 25967210
TI  - Analyzing closed-fringe images using two-dimensional Fan wavelets.
AB  - In this paper, it will be shown how the use of two 2D Fan wavelets to analyze
      closed-fringe images can lead to a relatively fast and exceptionally noise
      resistant algorithm capable of extracting not only local phase but also local
      frequency information. Our algorithm is up to 10 times faster than the current
      state-of-the-art in wavelet processing techniques and even up to 30 times faster
      than "windowed Fourier" transform programs, which achieve similar noise
      resiliency figures. This improvement is mainly achieved by the use of Fan
      wavelets instead of Morlet wavelets, but a more efficient scale-space
      discretization strategy is also described, and three different alternatives are
      suggested capable of solving the phase sign-ambiguity problem in a quick and
      efficient manner. Finally, the application of the algorithm to real and
      numerically generated images shows that a precision of 1/30th of a fringe is
      achievable for noise levels going up to 1/5th of the input contrast. 

PMID- 25967211
TI  - Parametric analysis of damage probability: a tool to identify weak layers within
      multilayer coatings.
AB  - The role of defects, inherent to fused silica substrate due to polishing and
      deposition processes, is interpreted in terms of laser-induced damage
      probability. Changes of damage threshold behavior are observed in bare substrate,
      monolayer, and multilayer coatings after irradiation with UV (355 nm) nanosecond
      laser pulses at different angles of incidence (0 degrees  and 45 degrees ) and
      polarizations (s and p). Statistical damage probability models are constructed
      for experimental data approximation. Effects of light intensification by standing
      waves within multilayer coatings and localization of the defects (surface,
      interface, and bulk) are considered as key factors within this work. Polishing
      defects are shown to be the limiting factor in the case of uncoated fused silica
      sample, as well as SiO2 and HfO2 monolayer coated substrates. The obtained
      results also suggest that damage threshold of almost identical sublayers
      constituting highly reflective multilayer HfO2/SiO2 coating with central 355 nm
      wavelength is a function of sublayer depth.

PMID- 25967212
TI  - Unsupervised defect detection in textiles based on Fourier analysis and wavelet
      shrinkage.
AB  - An unsupervised approach for the inspection of defects in textiles by applying
      Fourier analysis and wavelet shrinkage is proposed. It does not rely on any
      reference images. For each sample under inspection, the periodic pattern in the
      background is first eliminated by zero-masking their dominant frequency
      components that show high gradient values in the spectrum. The Fourier-restored
      residual image is then denoised by wavelet shrinkage. The approximation
      coefficients and the processed wavelet coefficients are individually back
      transformed to produce a pair of reconstructions from which either the low or the
      high-frequency information about the defects can be segmented using a simple
      thresholding process. The performance of the method has been extensively
      evaluated by a wide variety of samples with different defect types and texture
      backgrounds. The effectiveness of the proposed method is demonstrated by the
      experimental results in comparison with other methods. 

PMID- 25967213
TI  - Instrument transfer function of slope measuring deflectometry systems.
AB  - Slope measuring deflectometry (SMD) systems are developing rapidly in testing
      freeform optics. They measure the surface slope using a camera and an incoherent
      source. The principle of the test is mainly discussed in geometric optic domain.
      The system response as a function of spatial frequency or instrument transfer
      function (ITF) has yet to be studied thoroughly. Through mathematical modeling,
      simulation, and experiment we show that the ITF of an SMD system is very close to
      the modulation transfer function of the camera used. Furthermore, the ITF can be
      enhanced using a deconvolution filter. This study will lead to more accurate
      measurements in SMD and will show the physical optics nature of these tests. 

PMID- 25967214
TI  - Correction of large retardation window effect for ellipsometry measurements using
      quasi-Newton method.
AB  - Optical windows attached to the sample chamber for ellipsometry measurements
      often manifest stress-induced retardation. In reality, the retardation is not
      always small enough to be simplified with the small angle approximation, varies
      within the optical beam, and furthermore may change with the evolution of the
      environmental conditions of the chamber. Large retardations and retardation
      distributions result in complicated Mueller matrices of the input window-sample
      output window system. Consequently, extensive computation is required to obtain
      the true ellipsometric parameters (Delta,Psi) of the sample. In this paper, we
      show that the quasi-Newton method can be used to simultaneously obtain 14 unknown
      parameters (including ellipsometric parameters) from the Mueller matrix, with a
      single measurement under conditions of large and inhomogeneous window
      retardation. A limitation of the method is that it is valid only for isotropic
      samples. The validity of the method has been tested using a set of samples: a
      silicon substrate, a TiN-coated silicon wafer, and a thermally grown silicon
      dioxide film. Measurements were done under the window effect and corrected using
      the proposed method. The corrected results showed excellent agreement with
      ellipsometric parameters obtained without window effect. 

PMID- 25967215
TI  - Periodic modulation-based spectral and temporal superresolution with a single
      measurement.
AB  - In a superresolution technique, based on periodic modulation of the signal to be
      tested, high resolution is obtained for a large number of modulation harmonics.
      However, the number of measurements, required for measuring one quantity, is
      equal to the number of harmonics. Two techniques of spectral and temporal
      superresolution with a single measurement, based on replication of the signal,
      are proposed and numerically demonstrated. In the first one, replication and
      modulation lead to sampling and compression in the Fourier transform domain. It
      is shown that an optical spectrum analyzer with a resolution of 0.01 nm (1.25
      GHz) is capable of measuring 1 MHz spectral lines with a resolution of 60 kHz,
      using the superresolution technique proposed. The spectrum is magnified by a
      factor of 10,000. Similarly, the measurement of 1.7 ps optical pulses with a
      resolution of 44 fs can be performed with a 30 GHz real-time oscilloscope. The
      magnification factor is 160. In the second proposed method, the parts of the
      signal Fourier transform for each replica are shifted into the system passband.
      This method is useful for measurement of very long single-shot ultrafast temporal
      waveforms.

PMID- 25967216
TI  - Simulation, fabrication, and characterization of a tunable electrowetting-based
      lens with a wedge-shaped PDMS dielectric layer.
AB  - Microlenses with tunable focal length have wide applications in optofluidic
      devices. This work presents a numerical and experimental investigation on a
      tunable electrowetting-based concave lens. Optical properties such as focal
      length of the lens and visibility of images were investigated numerically and
      experimentally. A finite element analysis and a ZEMAX simulation were used for
      determination of surface profile and focal length of the lens. The results show
      that the theoretical surface profile and focal length of the lens are in good
      agreement with the experimental ones. The lens has a wide tuning focal length
      equal to 6.5 (cm). Because the polydimethylsiloxane (PDMS) layer is wedge shaped
      (as both the dielectric and hydrophobic layers), lower applied voltage is needed.
      A commercial program was used to find the focal length of the lens from maximum
      visibility value by tuning the applied voltage. 

PMID- 25967217
TI  - Wrapping-free phase retrieval with applications to interferometry, 3D-shape
      profiling, and deflectometry.
AB  - Phase unwrapping is probably the most challenging step in the phase retrieval
      process in phase-shifting and spatial-carrier interferometry. Likewise, phase
      unwrapping is required in 3D-shape profiling and deflectometry. In this paper, we
      present a novel phase retrieval method that completely sidesteps the phase
      unwrapping process, significantly eliminating the guessing in phase
      reconstruction and thus decreasing the time data processing. The proposed
      wrapping-free method is based on the direct integration of the spatial
      derivatives of the interference patterns under the single assumption that the
      phase is continuous. This assumption is valid in most physical applications.
      Validation experiments are presented confirming the robustness of the proposed
      method. 

PMID- 25967218
TI  - Analytical model of optical path difference in an end-pumped Yb:YAG thin-disk
      laser with nonuniform pumping light.
AB  - An analytical model of the thermal effect and optical path difference (OPD) of a
      thin-disk laser is developed by an arbitrary form pumping spot. Based on the
      analytical model, the distribution of temperature, stress, and strain can be
      derived using a super-Gaussian form pumping spot. The total OPD caused by
      temperature gradient, axial thermal strain, thermal strain-induced birefringence,
      and deformation of the thin-disk crystal is discussed for different super
      Gaussian factors and is separated into spherical and aspherical parts. The
      analytical results show that the aspherical part of the OPD is the main reason
      leading to the decrease of the laser beam quality and it is closely related to
      super-Gaussian factors, which are very useful for thin-disk laser design and
      evaluation. 

PMID- 25967219
TI  - Stable dual-wavelength Q-switched Nd:YAG laser using a two-step energy extraction
      technique.
AB  - The generation of stable dual-wavelength pulses from an actively Q-switched
      Nd:YAG laser operating at 1064 and 1319 nm was demonstrated. Pulse energies of
      the dual-wavelength laser were extracted by two temporally separated stimulated
      emission processes for a single pumping process, thereby avoiding line
      competition between the two laser transitions. Total energy of the order of 20 mJ
      was achieved for the two pulses, and the ratio of the pulse energies of the two
      lasers could be selected by adjusting the output couplings. The pulse-to-pulse
      fluctuations for the lasers operating at 1319 and 1064 nm were 4.7%-4.8% and 1.5%
      2.6%, respectively, which were almost equivalent to those for a single emission
      line in our system. The experimentally observed laser performance agreed
      reasonably well with theoretical predictions.

PMID- 25967220
TI  - Dielectric function of very thin nano-granular ZnO layers with different states
      of growth.
AB  - Zinc oxide (ZnO) layers consisting of grains closely packed together are grown
      using a solgel synthesis and spin-coating deposition process. The morphologies
      are characterized by atomic force microscopy and X-ray diffraction, and their
      optical properties are investigated by spectroscopic ellipsometry at the
      different stages of the growth process. The optical observations are correlated
      with evolution of morphology and orientation. Two remarkable evolutions are
      observed: gradual evolution of morphology, crystallinity, and excitonic
      contribution with the first deposition steps; and transformation from a poorly
      oriented to a c-axis oriented crystalline state featuring a large contribution of
      bound excitons after thermal annealing. A modified Elliott model is used to
      obtain the optical parameters of ZnO, including bandgap and exciton energies. A
      simple growth mechanism is proposed to explain the evolution of the layers in
      accordance with the different deposition steps. 

PMID- 25967221
TI  - Fiber-based distance sensing interferometry.
AB  - We present an interferometric displacement sensor based on a folded low-finesse
      Fabry-Perot cavity. The fiber-optic sensor uses a quadrature detection scheme
      based on the wavelength modulation of a DFB laser. This enables measuring
      position changes over a range of 1 m for velocities up to 2 m/s. The sensor is
      well suited to work in extreme environments such as ultrahigh vacuum, cryogenic
      temperatures, or high magnetic fields and supports multichannel applications. The
      interferometer achieves a repeatability of 0.44  nm(3sigma) at a working distance
      of 20 mm, a resolution of 1 pm, and an accuracy of 1 nm.

PMID- 25967222
TI  - Establishment and application of the 0/45 reflectance factor scale over the
      shortwave infrared.
AB  - This paper describes the establishment and application of the 0/45 reflectance
      factor scale in the shortwave infrared (SWIR) from 1100 to 2500 nm. Design,
      characterization, and the demonstration of a four-stage, extended indium-gallium
      arsenide radiometer to perform reflectance measurements in the SWIR have been
      previously discussed. Here, we focus on the incorporation of the radiometer into
      the national reference reflectometer, its validation through comparison
      measurements, and the uncertainty budget. Next, this capability is applied to the
      measurement of three different diffuser materials. The 0/45 spectral reflectance
      factors for these materials are reported and compared to their respective 6/di
      spectral reflectance factors.

PMID- 25967223
TI  - Development and application of spherically curved charge-coupled device imagers.
AB  - Operation of a CCD imager on a curved focal surface offers advantages to flat
      focal planes, especially for lightweight, relatively simple optical systems. The
      first advantage is that the modulation transfer function can approach diffraction
      limited performance for a spherical focal surface employed in large field-of-view
      or large-format imagers. The second advantage is that a curved focal surface
      maintains more uniform illumination as a function of radius from the field
      center. Examples of applications of curved imagers, described here, include a
      small compact imager and the large curved array used in the Space Surveillance
      Telescope. The operational characteristics and mechanical limits of an imager
      deformed to a 15 mm radius are also described.

PMID- 25967224
TI  - Optical design method for minimization of ghost stray light intensity.
AB  - A method for minimizing the intensity of ghost stray light during the optical
      design process is presented in this paper. Dimensions and, consequently,
      intensities of ghost images formed in an optical system can be estimated using an
      analytical algorithm. This algorithm enables construction of a merit function in
      optical design software, which returns a number proportional to the total
      intensity of ghost stray light. In this way, an optical system can be
      simultaneously optimized for the best image quality and for the minimum ghost
      stray light intensity. The proposed method has been applied to reoptimize a
      diffraction-limited system of four lenses, and a reduction of ghost stray light
      by a factor of 6 with almost no degradation of image quality has been achieved. 

PMID- 25967226
TI  - Pegylated interferon alfa for chronic hepatitis B: systematic review and meta
      analysis.
AB  - Conventional interferon alfa and nucleos(t)ide analogues, such as lamivudine, are
      frequently used for chronic hepatitis B (CHB) treatment, but are associated with
      adverse effects and viral resistance. Here we performed a systematic review and
      meta-analysis evaluating all studies of pegylated interferon alfa (PEG-IFNalpha)
      treatment in hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients
      with CHB. We searched electronic databases--PubMed, EMBASE, Cochrane Library and
      LILACS--for randomized controlled trials evaluating PEG-IFNalpha therapy between
      1999 and September 2014. Virological response was the primary outcome. We
      identified 14 studies involving 2829 patients. Our analysis revealed that PEG
      IFNalpha + lamivudine combination therapy produced better virological and
      biochemical responses than PEG-IFNalpha monotherapy in HBeAg-positive and HBeAg
      negative patients at the end of treatment. PEG-IFNalpha + adefovir dipivoxil
      achieved better seroconversion rate than PEG-IFNalpha in HBeAg-positive patients
      at the end of treatment. The present findings demonstrated a beneficial response
      rate following PEG-IFNalpha combination therapy with nucelos(t)ides among HBeAg
      positive and HBeAg-negative patients with CHB. Further trials are needed to
      investigate simultaneous and sequential therapy strategies.

PMID- 25967227
TI  - Serum GDF15 Levels Correlate to Mitochondrial Disease Severity and Myocardial
      Strain, but Not to Disease Progression in Adult m.3243A>G Carriers.
AB  - In this observational cohort study, we examined the prognostic value of growth
      and differentiation factor 15 (GDF15) in indicating and monitoring general
      mitochondrial disease severity and progression in adult carriers of the m.3243A>G
      mutation.Ninety-seven adult carriers of the m.3243A>G mutation were included in
      this study. The Newcastle mitochondrial disease adult scale was used for rating
      mitochondrial disease severity. In parallel, blood was drawn for GDF15 analysis
      by ELISA. Forty-nine carriers were included in a follow-up study. In a small
      subset of subjects of whom an echocardiogram was available from general patient
      care, myocardial deformation was assessed using two-dimensional speckle-tracking
      strain analysis.A moderate positive correlation was found between the
      concentration of GDF15 and disease severity (r = 0.59; p < 0.001). The
      concentration of serum GDF15 was higher in m.3243A>G carriers with diabetes
      mellitus, cardiomyopathy, and renal abnormalities. After a 2-year follow-up, no
      significant correlation was found between the change in disease severity and the
      change in the concentration of GDF15 or between the GDF15 level at the first
      assessment and the change in disease severity. In the subcohort of patients of
      whom an echocardiogram was available, the concentration of GDF15 correlated
      moderately to longitudinal global strain (r = 0.55; p = 0.006; n = 23) but not to
      circumferential or radial strain.Our results indicate that serum GDF15 is not a
      strong surrogate marker for general mitochondrial disease severity. Its value in
      indicating myocardial deformation should be confirmed in a prospective
      longitudinal study. 

PMID- 25967228
TI  - Rhabdomyolysis-Associated Mutations in Human LPIN1 Lead to Loss of Phosphatidic
      Acid Phosphohydrolase Activity.
AB  - Rhabdomyolysis is an acute syndrome due to extensive injury of skeletal muscle.
      Recurrent rhabdomyolysis is often caused by inborn errors in intermediary
      metabolism, and recent work has suggested that mutations in the human gene
      encoding lipin 1 (LPIN1) may be a common cause of recurrent rhabdomyolysis in
      children. Lipin 1 dephosphorylates phosphatidic acid to form diacylglycerol
      (phosphatidic acid phosphohydrolase; PAP) and acts as a transcriptional
      regulatory protein to control metabolic gene expression. Herein, a 3-year-old boy
      with severe recurrent rhabdomyolysis was determined to be a compound heterozygote
      for a novel c.1904T>C (p.Leu635Pro) substitution and a previously reported
      genomic deletion of exons 18-19 (E766-S838_del) in LPIN1. Western blotting with
      patient muscle biopsy lysates demonstrated a marked reduction in lipin 1 protein,
      while immunohistochemical staining for lipin 1 showed abnormal subcellular
      localization. We cloned cDNAs to express recombinant lipin 1 proteins harboring
      pathogenic mutations and showed that the E766-S838_del allele was not expressed
      at the RNA or protein level. Lipin 1 p.Leu635Pro was expressed, but the protein
      was less stable, was aggregated in the cytosol, and was targeted for proteosomal
      degradation. Another pathogenic single amino acid substitution, lipin 1
      p.Arg725His, was well expressed and retained its transcriptional regulatory
      function. However, both p.Leu635Pro and p.Arg725His proteins were found to be
      deficient in PAP activity. Kinetic analyses demonstrated a loss of catalysis
      rather than diminished substrate binding. These data suggest that loss of lipin 1
      mediated PAP activity may be involved in the pathogenesis of rhabdomyolysis in
      lipin 1 deficiency. 

PMID- 25967229
TI  - Dup-24 bp in the CHIT1 Gene in Six Mexican Amerindian Populations.
AB  - Chitotriosidase (CHIT, EC 3.2.1.14) is an enzyme secreted by activated
      macrophages with the ability to hydrolyze the chitin of pathogens. The high
      activity of this enzyme has been used as a secondary biomarker of response to
      treatment in patients with Gaucher disease (OMIM 230800). Within the world's
      population, approximately 6% is homozygous and 35% is heterozygous for the most
      common polymorphism in the CHIT1 gene, a 24-bp duplication (dup-24 bp), with
      homozygosity of this duplication causing inactivation of the enzyme but without
      major consequences for health. To determine the frequency of the dup-24 bp CHIT1
      gene in indigenous populations from Mexico, 692 samples were analyzed: Purepecha
      (49), Tarahumara (97), Huichol (97), Mayan (139), Tenek (97), and Nahua (213). We
      found that the groups were in Hardy-Weinberg equilibrium. The dup-24 bp allele
      frequency was found to be (in order of highest to lowest) 37% (Mayan), 34%
      (Huichol and Nahua), 33% (Purepecha), 31% (Tenek), and 29% (Tarahumara). 

PMID- 25967230
TI  - Novel Genetic Mutations in the First Swedish Patient with Purine Nucleoside
      Phosphorylase Deficiency and Clinical Outcome After Hematopoietic Stem Cell
      Transplantation with HLA-Matched Unrelated Donor.
AB  - Purine nucleoside phosphorylase (PNP) is an enzyme active in the purine salvage
      pathway. PNP deficiency caused by autosomal recessive mutations in the PNP gene
      leads to severe combined immunodeficiency (SCID) and in two thirds of cases also
      to neurological effects such as developmental delay, ataxia, and motor
      impairment.PNP deficiency has a poor outcome, and the only curative treatment is
      allogenic hematopoietic stem cell transplantation (HSCT). We present the first
      Swedish patient with PNP deficiency with novel mutations in the PNP gene and the
      immunological results of the HSCT and evaluate the impact of HSCT on the
      neurological symptoms. The patient presented early in life with neurological
      symptoms and suffered later from repeated serious respiratory tract infections.
      Biochemical tests showed severe reduction in PNP activity (1% residual activity).
      Genetic testing revealed two new mutations in the PNP gene: c.729C>G
      (p.Asn243Lys) and c.746A>C (p.Tyr249Cys). HSCT was performed with an unrelated
      donor, resulting in prompt and sustained engraftment and complete donor
      chimerism. There was no further aggravation of the patient's neurological
      symptoms at 21 months post HSCT, and appropriate developmental milestones were
      achieved. HSCT is curative for the immunological defect caused by PNP deficiency,
      and our case strengthens earlier reports that HSCT is effective as a treatment
      even for neurological symptoms in PNP deficiency. 

PMID- 25967231
TI  - A Novel Catastrophic Presentation of X-Linked Adrenoleukodystrophy.
AB  - OBJECTIVE: We report a novel presentation of childhood cerebral X-linked
      adrenoleukodystrophy: status epilepticus followed by abrupt and catastrophic
      neurologic deterioration. METHODS: A description of the clinical presentation,
      laboratory evaluation, and imaging findings leading to a diagnosis of X-linked
      adrenoleukodystrophy. RESULTS: A 3-year-old male with prior history of autism
      presented with fever, diarrhea, and status epilepticus requiring a pentobarbital
      coma. Admission labs were notable only for a glucose level of 22 mg/dL, which
      stabilized after correction. The child never returned to his prior neurologic
      baseline, with complete loss of gross motor, fine motor, and speech skills.
      Serial brain magnetic resonance imaging (MRI)/magnetic resonance spectroscopy
      (MRS) was notable for progressive diffuse cortical signal changes with swelling,
      diffusion restriction, and ultimately laminar necrosis. Nine months after
      presentation, CSF (cerebrospinal fluid) protein and MRS lactate were persistently
      elevated, concerning for a neurodegenerative disorder. This led to testing for
      mitochondrial disease, followed by lysosomal and peroxisomal disorders. Very long
      chain fatty acids were elevated. Identification of a pathogenic ABCD1 mutation
      confirmed the diagnosis of X-linked adrenoleukodystrophy. CONCLUSIONS: Boys with
      childhood cerebral X-linked adrenoleukodystrophy typically present with gradual
      behavioral changes. Rare reports of boys presenting with transient altered mental
      status or status epilepticus describe a recovery to their pre-presentation
      baseline. To our knowledge this is the first X-ALD patient to present with status
      epilepticus with abrupt and catastrophic loss of neurologic function. X-linked
      adrenoleukodystrophy should be suspected in young males presenting with seizures,
      acute decline in neurologic function, with persistently elevated CSF protein and
      MRS lactate.

PMID- 25967232
TI  - High Incidence of Biotinidase Deficiency from a Pilot Newborn Screening Study in
      Minas Gerais, Brazil.
AB  - OBJECTIVE: To assess the incidence of biotinidase deficiency among newborns and
      their clinical outcome up to one year of age in a large pilot screening study in
      Minas Gerais, Brazil. METHODS: A prospective cohort study was conducted from
      September 2007 to June 2008 with heel-prick blood samples collected on filter
      paper for the purpose of newborn screening. A qualitative colorimetric test was
      used as the primary screening method. Colorimetric-positive cases were further
      tested with a serum confirmatory assay. Gene sequencing was performed for eight
      children suspected with biotinidase deficiency and for some of their parents.
      Positive cases were daily supplemented with oral biotin and were followed up for
      approximately six years. RESULTS: Out of 182,891 newborns screened, 129 were
      suspected of having biotinidase deficiency. Partial deficiency was confirmed in
      seven children (one was homozygous for p.D543E) and profound deficiency in one
      child (homozygous p.H485Q). Thus the incidence was one in 22,861 live births (95%
      confidence interval 1:13,503 to 1:74,454) for profound and partial biotinidase
      deficiency combined. Two novel mutations were detected: p.A281V and p.E177K. In
      silico analysis and estimation of the enzyme activity in the children and their
      parents showed that p.A281V is pathogenic and p.E177K behaves like p.D444H.
      CONCLUSION: The incidence of biotinidase deficiency in newborn screening in Minas
      Gerais was higher than several international studies. The sample size should be
      larger for final conclusions. Oral daily biotin apparently precluded clinical
      symptoms, but it may have been unnecessary in some newborns.

PMID- 25967233
TI  - Anaphylaxis to Intravenous Ranitidine in a Child.
AB  - Although reversible H2 receptor antagonists are usually well tolerated, there are
      few reports on anaphylactic reactions triggered by ranitidine. Here we report the
      first case of anaphylaxis to ranitidine in a child. This was an IgE-mediated
      event occurring in a patient who had never used ranitidine before.

PMID- 25967235
TI  - Occurrence and recall rates of fertility discussions with young breast cancer
      patients.
AB  - PURPOSE: Fertility preservation is an important issue for premenopausal cancer
      patients; however, not all patients receive counseling about chemotherapy-induced
      infertility and potential mitigation strategies. We aimed to identify
      characteristics of premenopausal breast cancer patients less likely to receive
      fertility counseling. We also investigated patient recall of chart-documented
      fertility discussions and patient attitudes toward fertility preservation.
      METHODS: The study was approved by our institution's Institutional Review Board.
      All female patients with invasive primary breast cancer of any type, aged 40 or
      younger at the time of diagnosis, who were diagnosed during or up to 5 years
      prior to the study period were eligible. The study was conducted between February
      2012 and October 2013. Enrolled patients completed an anonymous survey, and their
      medical charts were subsequently reviewed to identify provider documentation of
      fertility discussions, referral to fertility specialists, or implementation of
      fertility preservation. Patient comments regarding their fertility were solicited
      and examined thematically. RESULTS: Forty-nine patients consented to participate.
      Fertility discussions were documented by providers in 55% of patients. Patients
      aged over 35 and multiparous patients were significantly less likely than their
      counterparts (p < 0.01 in both cases) to have had chart-documented fertility
      discussions. Only 52% of patients with chart-documented discussions recalled
      having had such a conversation. Patient comments highlighted the difficulty of
      considering fertility at the time of diagnosis and also the risks and obstacles
      facing fertility preservation. CONCLUSIONS: Despite increasing awareness,
      fertility is not universally discussed with premenopausal breast cancer patients
      at the time of diagnosis; older and multiparous patients are at particular risk
      of not receiving fertility counseling. Even when such discussions are documented,
      only about half of patients recall the conversation. Patient-reported barriers to
      fertility preservation include lack of education combined with the stress of
      diagnosis, financial costs, and perceived treatment toxicities.

PMID- 25967234
TI  - Do relevant markers of cancer stem cells CD133 and Nestin indicate a poor
      prognosis in glioma patients? A systematic review and meta-analysis.
AB  - BACKGROUND: CD133 and Nestin, as the markers of cancer stem cells, have recently
      been reported frequently in the pathogenesis and development of human gliomas.
      However, the prognostic role of CD133 and Nestin in gliomas still remains
      controversial. In this study, we aimed to evaluate the association between the
      expression of CD133 and Nestin and the outcome of glioma patients by conducting a
      systematic review and meta-analysis. METHODS: We performed systematically
      electronic and manual searches through the database of Pubmed and embase (until
      to December 25, 2014) for titles and abstracts which investigated the
      relationships between CD133 and Nestin expression and outcome of glioma patients.
      A systematic review and meta-analysis was executed to generate Pooled hazard
      ratios (HRs) with 95 % confidence intervals (CIs) for overall survival (OS) and
      progression-free survival (PFS). RESULTS: A total of 1,490 patients from 32
      studies (13 articles) were included in the analysis. 19 studies and 13 studies
      investigated correlation between CD133 expression or Nestin and survival in
      gliomas, respectively. Our results showed that high CD133 expression in patients
      with glioma was associated with poor prognosis in terms of OS (HR 1.69; 95 % CI,
      1.16-2.47; P =0.0060) and PFS (HR, 1.64; 95 % CI, 1.12-2.39; P = 0.010). In
      addition, high Nestin expression were associated with worse OS (HR 1.751; 95 %
      CI, 1.19-2.58, p = 0.004) but has no significant association with PFS (HR 1.55;
      95 % CI, 0.96-2.51, p = 0.074). Even more important, the results of the subgroup
      meta-analyses show that that high CD133 expression was associated with worse
      prognosis in terms of OS and PFS in patients with WHO IV glioma but not WHO II
      III. On the other hand, Nestin high expression was associated with worse
      prognosis in terms of OS and PFS in patients with WHO II-III glioma but not WHO
      IV. CONCLUSION: High level of CD133 expression trends to correlate with a worse
      OS and PFS in glioma patients, especially WHO IV gliomas and Nestin high
      expression trends to correlate with a worse OS in glioma patients especially WHO
      II-III, revealing both the markers of cancer stem cells may as the potential
      pathological prognostic markers for glioma patients.

PMID- 25967236
TI  - Familial versus Sporadic Essential Tremor: What Patterns Can One Decipher in Age
      of Onset?
AB  - BACKGROUND: Essential tremor (ET) is a very prevalent neurological disease.
      Although familial and sporadic ET cases are assumed to have different age at
      onset distributions, no detailed study of this question has been carried out.
      METHODS: Using a carefully characterized sample of 376 ET cases (232 (61.7%)
      familial) enrolled in a clinical-epidemiological study, we contrasted the age of
      onset distributions in familial versus sporadic ET. RESULTS: Familial ET had a
      lower age at onset distribution, regardless of the current age. The majority (71
      (86.6%) of 82) of ET cases that appeared during childhood were familial rather
      than sporadic. Additionally, the onset of ET occurred after age 40 in a majority
      of cases (125 (53.9%) of 232 with familial ET and 118 (81.9%) of 144 with
      sporadic ET), and in approximately one-quarter to one-half of cases, after age
      60. CONCLUSIONS: The age of onset of ET differs between familial and sporadic ET
      and furthermore, is variable within each of these groups. The onset of ET during
      childhood is usually familial, and the small number of identified exceptions
      could be due to de novo mutations. Understanding the heterogeneity in onset age
      will provide insights into the nature of underlying etiological and patho
      biological processes about which little is presently known.

PMID- 25967238
TI  - The focal adhesion kinase Pyk2 links Ca2+ signalling to Src family kinase
      activation and protein tyrosine phosphorylation in thrombin-stimulated platelets.
AB  - In blood platelets, stimulation of G protein-coupled receptors (GPCRs) by
      thrombin triggers the activation of Src family kinases (SFKs), resulting in the
      tyrosine-phosphorylation of multiple substrates, but the mechanism underlying
      this process is still poorly understood. In the present study, we show that the
      time-dependent protein-tyrosine phosphorylation triggered by thrombin in human or
      murine platelets was totally suppressed only upon concomitant chelation of
      intracellular Ca(2+) and inhibition of SFKs. Thrombin-induced activation of SFKs
      was regulated by intracellular Ca(2+) and accordingly the Ca(2+) ionophore A23187
      was sufficient to stimulate SFKs. A23187 also triggered the phosphorylation and
      activation of the Ca(2+)-dependent focal adhesion kinase Pyk2 and Pyk2 activation
      by thrombin was Ca(2+)-dependent. Stimulation of SFKs by thrombin or A23187 was
      strongly reduced in platelets from Pyk2 knockout (KO) mice, as was the overall
      pattern of protein-tyrosine phosphorylation. By immunoprecipitation experiments,
      we demonstrate that Lyn and Fyn, but not Src, were activated by Pyk2. Inhibition
      of SFKs by PP2 also reduced the phosphorylation of Pyk2 in thrombin or A23187
      stimulated platelets. Analysis of KO mice demonstrated that Fyn, but not Lyn, was
      required for complete Pyk2 phosphorylation by thrombin. Finally, PP2 reduced
      aggregation of murine platelets to a level comparable to that of Pyk2-deficient
      platelets, but did not have further effects in the absence of Pyk2. These results
      indicate that in thrombin-stimulated platelets, stimulation of Pyk2 by
      intracellular Ca(2+) initiates SFK activation, establishing a positive loop that
      reinforces the Pyk2/SFK axis and allows the subsequent massive tyrosine
      phosphorylation of multiple substrates required for platelet aggregation. 

PMID- 25967239
TI  - [Point-of-care tests and acute respiratory infections].

PMID- 25967240
TI  - [Pancreas cyst--a new access].

PMID- 25967237
TI  - Aberrant Activation of TGF-beta in Subchondral Bone at the Onset of Rheumatoid
      Arthritis Joint Destruction.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease that often leads to joint
      destruction. A myriad of drugs targeting the immune abnormalities and downstream
      inflammatory cascades have been developed, but the joint destruction is not
      effectively halted. Here we report that aberrant activation of TGF-beta in the
      subchondral bone marrow by immune response increases osteoprogenitors and
      uncoupled bone resorption and formation in RA mouse/rat models. Importantly,
      either systemic or local blockade of TGF-beta activity in the subchondral bone
      attenuated articular cartilage degeneration in RA. Moreover, conditional deletion
      of TGF-beta receptor II (Tgfbr2) in nestin-positive cells also effectively halted
      progression of RA joint destruction. Our data demonstrate that aberrant
      activation of TGF-beta in the subchondral bone is involved at the onset of RA
      joint cartilage degeneration. Thus, modulation of subchondral bone TGF-beta
      activity could be a potential therapy for RA joint destruction.

PMID- 25967241
TI  - [Medicine--the double-edged sword].

PMID- 25967242
TI  - [Thyroidectomy as day surgery operation: Is there a limit?].

PMID- 25967243
TI  - [Thiazide diuretics in the treatment of hypertensive patients].
AB  - This Cochrane review had the objectives to determine the dose-related decrease in
      blood pressure due to thiazide diuretics compared with placebo control in the
      treatment of hypertensive patients. Hydrochlorothiazide has a dose-related blood
      pressure-lowering effect over the dose range 6.25, 12.5, 25 and 50 mg/day of 4/2,
      6/3, 8/3 and 11/5 mmHg, respectively. This exceeds the mean 3 mmHg reduction
      achieved by angiotensin-converting-enzyme inhibitors and angiotensin receptor
      blockers as shown in other Cochrane reviews, which have compared these
      antihypertensive drugs with placebo having used similar inclusion/exclusion
      criteria. 

PMID- 25967244
TI  - [Significant symptom relief after aspiration of a large simple renal cyst].

PMID- 25967246
TI  - [Marked effect of ECT in the treatment of mania].
AB  - Mania in bipolar affective disorder can be a serious condition which is usually
      treated with antipsychotics and mood stabilizers. A systematic search was carried
      out to review the literature concerning the efficacy of electroconvulsive therapy
      (ECT) in the treatment of mania. All available studies showed a marked effect of
      ECT with response/remission rates between 56 and 100%. The randomized controlled
      trials which compared ECT to pharmacotherapy found that ECT was superior to
      treatment with psychotropic drugs. 

PMID- 25967245
TI  - [Pulse oximetry screening of newborns can prevent circulatory collapse caused by
      congenital heart defect].
AB  - We present a case of total anomalous pulmonary venous drainage. Despite low
      oxygen saturation an eight-week-old girl had only minimal symptoms initially. She
      suffered collapse requiring acute surgical correction and prolonged intensive
      care. Her collapse and complicated post-operative course could have been avoided
      with earlier diagnosis. Infants with critical heart disease continue to be born
      undiagnosed despite prenatal ultrasound screening. There is evidence that infants
      with critical congenital heart defect can be detected by pulse oximetry
      screening, as is routine in Norway, Sweden and Finland, but not in Denmark. 

PMID- 25967247
TI  - [Therapeutic vaccines is a novel approach in castration-resistant prostate cancer
      treatment].
AB  - Castration-resistant prostate cancer (CRPC) is defined as tumour progression
      despite castrate levels of serum testosterone. During the past decade a number of
      new therapies, including chemotherapy and novel endocrine agents have been
      approved for CRPC treatment. The continued need for new effective drugs in CRPC
      has led to development of a novel therapeutic approach in CRPC treatment.
      Therapeutic vaccines activate the immune system to kill prostate cancer cells.
      This review describes recent pivotal phase 2 and 3 trials of CRPC vaccines and
      discusses the impact on future CRPC management. 

PMID- 25967248
TI  - [Quality of life of bariatric and body contouring].
AB  - Surgical treatment of obesity has led to a large group of patients with massive
      weight loss. The massive weight loss results in excessive skin, which leads to
      pain, skin problems, cosmetic discomfort and psychosocial issues. The impact on
      quality of life of bariatric and body contouring surgery can be measured by
      patient-specific, well-constructed psychometrically validated patient-reported
      outcome measures. A new patient-reported outcome measure, the Body-Q, has been
      translated for use in Danish patients. 

PMID- 25967249
TI  - [Injection of synthol in a bodybuilder can cause chronic wounds and ulceration].
AB  - In this case report we present a 45-year-old male bodybuilder, who had injected
      synthol and paraffin oil in both upper arms for augmentation purposes. This led
      to a circumference of 66 cm of his upper arms. His arms were rock solid and
      clearly deformed. Few years after the injections the patient suffered from
      spontaneous ulcerations on both arms. Conservative wound treatment with
      antibiotics and compression therapy had good effect on the ulcers of the right
      arm. The left arm needed surgical revision and negative pressure wound therapy
      preparing the tissue for a split skin graft. 

PMID- 25967250
TI  - A moving blocks empirical likelihood method for longitudinal data.
AB  - In the analysis of longitudinal or panel data, neglecting the serial correlations
      among the repeated measurements within subjects may lead to inefficient
      inference. In particular, when the number of repeated measurements is large, it
      may be desirable to model the serial correlations more generally. An appealing
      approach is to accommodate the serial correlations nonparametrically. In this
      article, we propose a moving blocks empirical likelihood method for general
      estimating equations. Asymptotic results are derived under sequential limits.
      Simulation studies are conducted to investigate the finite sample performances of
      the proposed methods and compare them with the elementwise and subject-wise
      empirical likelihood methods of Wang et al. (2010, Biometrika 97, 79-93) and the
      block empirical likelihood method of You et al. (2006, Can. J. Statist. 34, 79
      96). An application to an AIDS longitudinal study is presented. 

PMID- 25967251
TI  - Determination of the magnetostrictive response of nanoparticles via
      magnetoelectric measurements.
AB  - It is successfully demonstrated that nanoparticle's magnetostriction can be
      accurately determined based on the magnetoelectric effect measured on polymeric
      composite materials. This represents a novel, simple and versatile method for the
      determination of particle's magnetostriction at the nano scale and in their
      dispersed state, which has been, up to now, a difficult and imprecise task. 

PMID- 25967252
TI  - Pathologists are able to differentiate reliably the lamina propria associated
      with Barrett's musculofibrous anomaly from submucosa in oesophageal endoscopic
      resections.
AB  - AIMS: Endoscopic resection (ER) is the standard therapy for early oesophageal
      neoplasia and is used for diagnosis and treatment. Accurate staging is especially
      important, as further treatment depends on this. Because Barrett's mucosa often
      develops fibromuscular hyperplasia with a fibrotic lamina propria and
      reduplicated muscularis mucosae, pathologists have expressed concern that it may
      not be possible to differentiate lamina propria reliably from submucosa in such
      resections. This study aimed to develop criteria for distinguishing submucosa
      from abnormal lamina propria and test reproducibility. METHODS AND RESULTS:
      Virtual slides of oesophagectomy cases with early cancer were reviewed by
      participants, all gastrointestinal (GI) pathologists. Criteria were agreed for
      recognition of submucosa - the presence of any of submucosal glands, fat and
      large muscular vessels. A set of 20 endoscopic resections were then uploaded and
      45 areas annotated and participants asked to categorize as submucosa or lamina
      propria. Agreement was excellent, with 35 areas showing agreement by all
      pathologists and a further seven areas with four of five agreeing. Paired
      interobserver kappa values varied between 0.69 and 0.955. CONCLUSION: With the
      application of usually easily recognizable criteria, pathologists are able to
      differentiate submucosa from lamina propria with musculofibrous anomaly in
      oesophageal ER specimens with a high degree of reproducibility.

PMID- 25967253
TI  - An in silico expert system for the identification of eye irritants.
AB  - This report describes development of an in silico, expert rule-based method for
      the classification of chemicals into irritants or non-irritants to eye, as
      defined by the Draize test. This method was developed to screen data-poor
      cosmetic ingredient chemicals for eye irritancy potential, which is based upon
      exclusion rules of five physicochemical properties - molecular weight (MW),
      hydrophobicity (log P), number of hydrogen bond donors (HBD), number of hydrogen
      bond acceptors (HBA) and polarizability (Pol). These rules were developed using
      the ADMET Predictor software and a dataset of 917 eye irritant chemicals. The
      dataset was divided into 826 (90%) chemicals used for training set and 91 (10%)
      chemicals used for external validation set (every 10th chemical sorted by
      molecular weight). The sensitivity of these rules for the training and validation
      sets was 72.3% and 71.4%, respectively. These rules were also validated for their
      specificity using an external validation set of 2011 non-irritant chemicals to
      the eye. The specificity for this validation set was revealed as 77.3%. This
      method facilitates rapid screening and prioritization of data poor chemicals that
      are unlikely to be tested for eye irritancy in the Draize test. 

PMID- 25967254
TI  - Topically Applied Vancomycin Powder Reduces the Rate of Surgical Site Infection
      in Diabetic Patients Undergoing Foot and Ankle Surgery.
AB  - BACKGROUND: The purpose of this study was to evaluate the efficacy of topically
      applied vancomycin powder in reducing the rate of surgical site infections (SSIs)
      in patients with diabetes mellitus (DM) undergoing foot and ankle surgery.
      METHODS: Eighty-one patients with DM who underwent reconstructive surgery of a
      foot and/or ankle deformity and/or trauma and who received topically applied
      vancomycin were matched to 81 patients with DM who did not receive topically
      applied vancomycin. The mean age was 60.6 years in the vancomycin group and 59.4
      years in the control group (P < .05). The 2 groups were similar with regard to
      gender, body mass index, duration of DM, short-term and longer term glycemic
      control, and length of surgery. RESULTS: The overall likelihood of SSI was
      decreased by 73% in patients who received topically applied vancomycin (odds
      ratio [OR], 0.267; 95% CI, 0.089-0.803; P = .0188). The rate of superficial
      infection was not significantly different between the 2 groups (OR, 0.400; 95%
      CI, 0.078-2.062; P = .2734); however, deep infections were 80% less likely in
      patients who received vancomycin powder (OR, 0.200; 95% CI, 0.044-0.913; P =
      .0377). CONCLUSION: High-risk diabetic patients undergoing foot and ankle surgery
      were notably less likely to develop an SSI with the use of topically applied
      vancomycin powder in the surgical wound, particularly with regard to deep
      infections. Topically applied vancomycin was associated with a very low rate of
      complications and was inexpensive ($5 per 1000 mg). Based on this study, foot and
      ankle surgeons may consider applying 500 to 1000 mg of vancomycin powder prior to
      skin closure in diabetic patients who are not allergic to vancomycin. LEVEL OF
      EVIDENCE: Level III, retrospective case control series.

PMID- 25967255
TI  - Evaluation of Peripheral Neuropathy of Unknown Origin in an Outpatient Foot and
      Ankle Practice.
AB  - BACKGROUND: The foot and ankle surgeon can see peripheral neuropathy in the
      treatment of foot and ankle conditions. The purpose of this study was (1) to
      evaluate the demographics and presenting complaints of patients diagnosed with
      idiopathic peripheral neuropathy during an examination by a foot and ankle
      surgeon and (2) to identify the type and frequency of subsequent diagnosis of
      medical causes of neuropathy. METHODS: This was a retrospective study of patients
      diagnosed with idiopathic peripheral neuropathy in our practice between January
      1997 and December 2008. Ninety-five patients were identified, and demographic
      data, presenting complaints, and medical comorbidities were extracted from the
      medical record. Examination findings of decreased sensation to Semmes Weinstein
      5.07 monofilament testing were documented, and electromyogram and nerve
      conduction study results were reviewed when available. Laboratory values were
      noted, as were neurologic evaluations performed to diagnose medical conditions
      associated with peripheral neuropathy. RESULTS: The most common presentation was
      foot pain, in 36 patients (38%). Ninety-one patients had Semmes Weinstein 5.07
      monofilament testing, with loss of protective sensation reported in 75 of the 91
      tested (82%). Only 30 of the 95 patients had electromyogram and nerve conduction
      study results available, with a test positive for peripheral neuropathy in 20 of
      the 30 tested. Thirty-two patients were evaluated by a neurologist. A specific
      cause was identified in 12 of the 32 seen by a neurologist. Of the total group of
      95 patients, 31 patients (33%) were diagnosed with a condition that may be
      associated with peripheral neuropathy. CONCLUSIONS: Thirty-three percent of the
      patients presenting to our clinic and given a diagnosis of idiopathic peripheral
      neuropathy were ultimately diagnosed with a medical cause of neuropathy-most
      commonly, diabetes. For those patients with idiopathic neuropathy, a spectrum of
      disease was encountered, including pain, ulcer, infection, and Charcot
      neuroarthropathy. LEVEL OF EVIDENCE: Level IV, retrospective case series.

PMID- 25967256
TI  - Rate of Union After Segmental Midshaft Shortening Osteotomy of the Lesser
      Metatarsals.
AB  - BACKGROUND: Current literature reports excellent rates of union following various
      lesser metatarsal osteotomy techniques. However, it is our experience that
      segmental midshaft shortening osteotomies heal very slowly and have a greater
      potential for nonunion than has previously been reported. The purpose of this
      study was to assess union rates and report the time required for segmental
      midshaft shortening osteotomies to achieve radiographic union. METHODS: We
      reviewed the charts and postoperative radiographs of 58 patients (representing 91
      osteotomies) who underwent segmental midshaft shortening osteotomies with
      internal fixation between January 2009 and December 2013. Radiographs were
      reviewed to determine when union was achieved. Union was defined as the bridging
      of 2 or more cortices in the anteroposterior, lateral, and oblique radiographic
      views. Osteotomies were classified as delayed union if they were not healed at 3
      months postoperatively and nonunions if they were not healed at 6 months
      postoperatively. RESULTS: Overall, 27 of 91 osteotomies met our radiographic
      classification of union and were healed by 3 months (29.7%). Sixty-nine of the 91
      osteotomies healed by 6 months (75.8%) and were considered delayed unions. Twenty
      two osteotomies were not healed yet and therefore were considered nonunions
      (24.2%). Of the 22 nonunions, 7 healed in an additional 2 months (8 months) for
      an overall healing percentage of 83.5%, (76 of 91). By 10 months, 6 more
      nonunions were healed (overall healing percentage of 90.1%, 82 of 91). Three
      additional nonunions went on to heal by 12.9 months, yielding a final union rate
      of 93.4% (85 of 91), while 6 were still considered nonunions (6.6%). CONCLUSION:
      We report that a significant percentage of segmental midshaft metatarsal
      shortening osteotomies experienced delayed unions and nonunions. These findings
      contrast those previously reported in the literature that metatarsal osteotomies
      have very low nonunion rates. These results support our hypothesis that these
      osteotomies require a prolonged amount of time to achieve bony healing and that
      they have a higher tendency to develop delayed and nonunions than previously
      reported. LEVEL OF EVIDENCE: Level IV, retrospective case series.

PMID- 25967257
TI  - Is Sinusitis Innocent?--Unilateral Subdural Empyema in an Immunocompetent Child.
AB  - Subdural empyema related to Streptococcus constellatus is extremely rare in an
      immunocompetent child, and also there is no reported case along with
      Staphylococcus lugdunensis infection. Although Streptococcus constellatus has
      been determined as a co-pathogen with anerobic bacteria in many infections, it
      has not been reported in combination with Staphylococcus lugdunensis. The authors
      describe a case of previously healthy 16-y-old child with unilateral subdural
      empyema due to these bacteria. Sinusitis was the only predisposing factor in the
      index case. The authors propose that some cases of culture-negative intracranial
      infections may be due to these infectious agents. Therefore, these agents should
      be considered as causes of intracranial infection in persistent complaints such
      as fever and headache after sinusitis in children. It is important to treat them
      with effective antibiotics and early surgical intervention for favorable outcome,
      because fatal cases were reported due to Streptococcus constellatus infections. 

PMID- 25967258
TI  - Variability in the Manifestations and Evolution of Symptoms in a Patient with H
      Syndrome.

PMID- 25967259
TI  - Vitamin D Deficiency and Critical Illness.
AB  - OBJECTIVE: To determine the prevalence of vitamin D deficiency in critically ill
      children and assess its association with severity of illness and other outcomes
      associated with critical illness. METHODS: Eighty children aged 2 mo to 12 y,
      admitted with medical conditions to the pediatric intensive care unit of a
      tertiary care hospital were enrolled in this prospective observational study.
      Vitamin D levels were obtained during the first hour of stay. Severity score was
      assessed using the Pediatric Risk of Mortality III (PRISM III) within first 12 h
      of admission. RESULTS: Vitamin D deficiency {25-hydroxy vitamin D [25(OH)D]
      levels < 20 ng/ml} was observed in 67 (83.8%) children. Vitamin D deficient
      children had significantly higher PRISM III score compared to vitamin D
      sufficient children [10 (IQR:5-15) vs. 6 (IQR:3-7); p 0.0099]. 25(OH)D levels had
      a significant negative correlation with PRISM III score (rho -0.3747; p 0.0006).
      CONCLUSIONS: Vitamin D appears to be of utmost importance in critically ill
      children.

PMID- 25967260
TI  - Comparison of Two New Generation Pulse Oximeters with Arterial Oxygen Saturation
      in Critically Ill Children: Authors' Reply.

PMID- 25967261
TI  - Comparison of Two New Generation Pulse Oximeters with Arterial Oxygen Saturation
      in Critically Ill Children: Correspondence.

PMID- 25967262
TI  - Increased false positive Down syndrome screening in women with sickle cell
      anemia.
AB  - OBJECTIVES: This study seeks to determine whether there is a higher rate of false
      positive serum screening for Down syndrome in women with sickle cell anemia and,
      if so, which markers contribute to the false positive screen. METHODS: This is a
      retrospective cohort study of women who had serum screening between 1998 and
      2011. Subjects were women with sickle cell anemia (n = 13), and controls were
      African American women who did not have that disease (n = 91). The populations
      were compared using basic inferential statistics. RESULTS: The positive screen
      rate was 38.5% (5/13) in women with sickle cell anemia and 7.7% (7/91) in the
      control population (odds ratio 7.5, 95% confidence interval 1.6-35.8, P = 0.001).
      At the average age of the cases (25 years), the expected false positive rate is
      only 2%. The human chorionic gonadotrophin values were significantly higher in
      cases than controls (2.00 and 1.30 MoM, P = 0.017), whereas levels of other serum
      analytes were similar. None of the screen positive results were associated with a
      fetus or neonate affected by Down syndrome. CONCLUSIONS: The false positive Down
      syndrome serum screen rate is significantly higher in patients with sickle cell
      anemia than in African American women without that disease. The human chorionic
      gonadotrophin values were significantly higher in cases than controls, suggesting
      that placental factors may contribute to the elevated false positive rate. (c)
      2015 John Wiley & Sons, Ltd.

PMID- 25967263
TI  - Ghrelin signaling in the ventral tegmental area mediates both reward-based
      feeding and fasting-induced hyperphagia on high-fat diet.
AB  - Ghrelin is a potent orexigenic hormone that acts in the central nervous system to
      stimulate food intake via the growth hormone secretagogue receptor (GHSR) that is
      abundantly expressed in the ventral tegmental area (VTA). Not only does ghrelin
      modulate feeding behavior via a homeostatic mechanism, but numerous studies have
      identified ghrelin as a key regulator of reward-based hedonic feeding behaviors.
      Nutritional states influence ghrelin and GHSR expression as well as the
      behavioral sensitivity to reward-inducing stimuli. In the current study, we
      examined the role of ghrelin at the VTA level in food intake in two different
      nutritional states, satiety and hunger, by using a restricted feeding model. In
      this model, rats were conditioned to a daily 3-h (h) feeding session on standard
      chow for 10days and a high-fat diet (HFD) was supplied either in the third hour
      after 2h of chow diet intake, or at the beginning of a daily meal on the test
      day. We found that intra-VTA microinjection of 1, 2, and 4MUg of ghrelin, induced
      a dose-related increase of 1h of reward-based feeding on HFD in sated rats, as
      well as a 24-h body weight gain. The overconsumption stimulated by ghrelin could
      be attenuated by 10MUg of direct infusion of the ghrelin receptor antagonist D
      Lys3-GHRP-6 into the VTA. Moreover, our data showed that the injection of 1, 2,
      and 4MUg of ghrelin in the VTA, enhanced fasting-induced hyperphagia on HFD in a
      dose-related manner following a 21-h food restriction as well as a 24-h body
      weight gain. Conversely, hyperphagia on HFD that is potentiated by ghrelin could
      be blocked by pretreatment with a 10-MUg D-Lys3-GHRP-6 intra-VTA microinjection.
      Collectively, these data demonstrate that ghrelin signaling at the VTA level
      mediates both reward-based eating and fasting-induced hyperphagia and provides a
      primary target for the control of the intake of rewarding food.

PMID- 25967264
TI  - Building up and knocking down: an emerging role for epigenetics and proteasomal
      degradation in systems consolidation.
AB  - Memory formation is a protracted process in which recently acquired events are
      consolidated to produce stable and specific associations. Initially, newly
      acquired information undergoes cellular consolidation in the hippocampus, which
      transiently supports the storage of recently acquired memories. In contrast,
      remote, or "old" memories are maintained in the cortex and show almost complete
      independence from the hippocampus. Memories are transferred from the hippocampus
      to the cortex through a process termed systems consolidation. Emerging evidence
      suggests that recurrent activation, or "training" of the cortex by the
      hippocampus is vital to systems consolidation. This process involves prolonged
      waves of memory-related gene activity in the hippocampus and cortex long after
      the learning event has terminated. Indeed, molecular events occurring within
      hours and days of fear conditioning are essential for stabilizing and eventually
      transitioning the memory to the cortex. It is increasingly evident that molecular
      mechanisms that exhibit a capacity for prolonged activation may underlie systems
      consolidation. Processes that have the capacity to control protein abundance over
      long time scales, such as epigenetic modifications, are prime candidates for the
      molecular mechanism of systems consolidation. Indeed, recent work has established
      two types of epigenetic modifications as integral for systems consolidation.
      First, localized nucleosomal histone variant exchange and histone modifications
      are integral for early stages of systems consolidation, whereas DNA methylation
      appears to be utilized to form stable marks that support memory maintenance.
      Since systems consolidation also requires discrete and time-sensitive changes in
      protein abundance, additional mechanisms, such as protein degradation, need also
      be considered, although their role in systems consolidation has yet to be
      investigated. Here, we discuss the role of molecular mechanisms in systems
      consolidation and their implications for understanding how memories persist over
      time.

PMID- 25967265
TI  - Covariation of pupillary and auditory cortical activity in rats under isoflurane
      anesthesia.
AB  - Very slow fluctuations of spontaneous activities significantly influence not only
      behavioral performance in a conscious state, but also neural activities in an
      unconscious state. Covariation of pupil and cortical activities may lend
      important insights into the state-dependent modulation of stimulus encoding, yet
      this phenomenon has received little attention, especially with regard to non
      visual cortices. In the present study, we investigated co-fluctuation of pupil
      size and neural activity in the auditory cortex of rats under isoflurane
      anesthesia. Pupil fluctuation consisted of longitudinal irregular shifts, and 1
      min cyclic modulations. Both spontaneous and auditory-evoked potentials (AEPs)
      covaried with the longitudinal fluctuation of pupil size, but not with the 1-min
      cycle. Pupil size exhibited a positive correlation with spontaneous activity and
      negative correlation with AEP amplitude, particularly when the pupil size was
      beyond the normal range. Stimulus-specific adaptation characterized using an
      oddball paradigm was less dependent on pupil size than AEP. In contrast to the
      cortical activity, heart rate covaried with pupil size with the 1-min oscillatory
      component, but not the non-oscillatory component. Furthermore, light exposure
      induced the pupil reflex through the autonomic system, but did not modify
      cortical activity, indicating that autonomic activity was not causing the
      cortical modulation. These results together suggest that cortical activities
      spontaneously covary with pupillary activity through central cholinergic
      modulation that triggers sympathetic nerve activation. Such a state-dependent
      property may be a confounding factor in cortical electrophysiology studies.

PMID- 25967266
TI  - Astroglial type-1 cannabinoid receptor (CB1): A new player in the tripartite
      synapse.
AB  - The endocannabinoid system is an important regulator of physiological functions.
      In the brain, this control is mainly exerted through the type-1-cannabinoid (CB1)
      receptors. CB1 receptors are abundant at neuron terminals where their stimulation
      inhibits neurotransmitter release. However, CB1 receptors are also expressed in
      astrocytes and recent studies showed that astroglial cannabinoid signaling is a
      key element of the tripartite synapse. In this review we discuss the different
      mechanisms by which astroglial CB1 receptors control synaptic transmission and
      plasticity. The recent involvement of astroglial CB1 receptors in the effects of
      cannabinoids on memory highlights their key roles in cognitive processes and
      further indicates that astrocytes are central active elements of high-order brain
      functions. 

PMID- 25967267
TI  - Spatial variability of muscle activity during human walking: the effects of
      different EMG normalization approaches.
AB  - Human leg muscles are often activated inhomogeneously, e.g. in standing. This may
      also occur in complex tasks like walking. Thus, bipolar surface electromyography
      (sEMG) may not accurately represent whole muscle activity. This study used 64
      electrode high-density sEMG (HD-sEMG) to examine spatial variability of lateral
      gastrocnemius (LG) muscle activity during the stance phase of walking, maximal
      voluntary contractions (MVCs) and maximal M-waves, and determined the effects of
      different normalization approaches on spatial and inter-participant variability.
      Plantar flexion MVC, maximal electrically elicited M-waves and walking at self
      selected speed were recorded in eight healthy males aged 24-34. sEMG signals were
      assessed in four ways: unnormalized, and normalized to MVC, M-wave or peak sEMG
      during the stance phase of walking. During walking, LG activity varied spatially,
      and was largest in the distal and lateral regions. Spatial variability fluctuated
      throughout the stance phase. Normalizing walking EMG signals to the peak value
      during stance reduced spatial variability within LG on average by 70%, and inter
      participant variability by 67%. Normalizing to MVC reduced spatial variability by
      17% but increased inter-participant variability by 230%. Normalizing to M-wave
      produced the greatest spatial variability (45% greater than unnormalized EMG) and
      increased inter-participant variability by 70%. Unnormalized bipolar LG sEMG may
      provide misleading results about representative muscle activity in walking due to
      spatial variability. For the peak value and MVC approaches, different electrode
      locations likely have minor effects on normalized results, whereas electrode
      location should be carefully considered when normalizing walking sEMG data to
      maximal M-waves.

PMID- 25967268
TI  - Tapering from Methadone or Buprenorphine during Pregnancy: Maternal and Neonatal
      Outcomes in Norway 1996-2009.
AB  - BACKGROUND: The tapering of methadone or buprenorphine during pregnancy is an
      understudied and controversial issue. The aim of this study was to determine to
      what extent women tapered their opioid medication dose during pregnancy and what
      the neonatal outcomes were for those who tapered compared to the women who did
      not. METHODS: The study was a mixed prospective/retrospective national cohort
      study of 123 Norwegian women in opioid maintenance treatment (OMT) during
      pregnancy and their neonates. A standardized questionnaire was administered to
      the women and medical information that could be used for verification was
      collected from hospitals and municipalities. RESULTS: Two of the women came off
      the OMT-medication during pregnancy and another 15% tapered their OMT-medication
      dose more than 50%. The birth weights of methadone-exposed neonates of the women
      who tapered more than 50% were significantly higher than for the methadone
      exposed neonates of the women tapering between 11 and 50%. No other significant
      differences were found. CONCLUSION: Pregnant women in OMT who taper their OMT
      medication dose should be monitored closely. We need studies that document the
      maternal well-being and fetal safety of maternal tapering of the OMT-medication
      during pregnancy.

PMID- 25967269
TI  - Implementation and Operational Research: Effects of Antenatal Care and HIV
      Treatment Integration on Elements of the PMTCT Cascade: Results From the SHAIP
      Cluster-Randomized Controlled Trial in Kenya.
AB  - BACKGROUND: Integrating antenatal care (ANC) and HIV care may improve uptake and
      retention in services along the prevention of mother-to-child transmission
      (PMTCT) cascade. This study aimed to determine whether integration of HIV
      services into ANC settings improves PMTCT service utilization outcomes. METHODS:
      ANC clinics in rural Kenya were randomized to integrated (6 clinics, 569 women)
      or nonintegrated (6 clinics, 603 women) services. Intervention clinics provided
      all HIV services, including highly active antiretroviral therapy (HAART), whereas
      control clinics provided PMTCT services but referred women to HIV care clinics
      within the same facility. PMTCT utilization outcomes among HIV-infected women
      (maternal HIV care enrollment, HAART initiation, and 3-month infant HIV testing
      uptake) were compared using generalized estimating equations and Cox regression.
      RESULTS: HIV care enrollment was higher in intervention compared with control
      clinics [69% versus 36%; odds ratio = 3.94, 95% confidence interval (CI): 1.14 to
      13.63]. Median time to enrollment was significantly shorter among intervention
      arm women (0 versus 8 days, hazard ratio = 2.20, 95% CI: 1.62 to 3.01). Eligible
      women in the intervention arm were more likely to initiate HAART (40% versus 17%;
      odds ratio = 3.22, 95% CI: 1.81 to 5.72). Infant testing was more common in the
      intervention arm (25% versus 18%), however, not statistically different. No
      significant differences were detected in postnatal service uptake or maternal
      retention. CONCLUSIONS: Service integration increased maternal HIV care
      enrollment and HAART uptake. However, PMTCT utilization outcomes were still
      suboptimal, and postnatal service utilization remained poor in both study arms.
      Further improvements in the PMTCT cascade will require additional research and
      interventions.

PMID- 25967270
TI  - Brief Intervention Decreases Drinking Frequency in HIV-Infected, Heavy Drinking
      Women: Results of a Randomized Controlled Trial.
AB  - OBJECTIVE: Hazardous alcohol use by HIV-infected women is associated with poor
      HIV outcomes and HIV transmission risk behaviors. We examined the effectiveness
      of brief alcohol intervention (BI) among hazardous drinking women receiving care
      in an urban HIV clinic. METHODS: Women were randomized to a 2-session BI or usual
      care. Outcomes assessed at baseline, 3, 6, and 12 months included 90-day
      frequency of any alcohol use and heavy/binge drinking (>=4 drinks per occasion),
      and average drinks per drinking episode. Secondary outcomes included HIV
      medication and appointment adherence, HIV-1 RNA suppression, and days of
      unprotected vaginal sex. We examined intervention effectiveness using generalized
      mixed-effect models and quantile regression. RESULTS: Of 148 eligible women, 74
      were randomized to each arm. In mixed-effects models, 90-day drinking frequency
      decreased among intervention group compared with control, with women in the
      intervention condition less likely to have a drinking day (odds ratio: 0.42; 95%
      confidence interval: 0.23 to 0.75). Heavy/binge drinking days and drinks per
      drinking day did not differ significantly between groups. Quantile regression
      demonstrated a decrease in drinking frequency in the middle to upper ranges of
      the distribution of drinking days and heavy/binge drinking days that differed
      significantly between intervention and control conditions. At follow-up, the
      intervention group had significantly fewer episodes of unprotected vaginal sex.
      No intervention effects were observed for other outcomes. CONCLUSIONS: BI reduces
      frequency of alcohol use and unprotected vaginal sex among HIV-infected women.
      More intensive services may be needed to lower drinks per drinking day and
      enhance care for more severely affected drinkers.

PMID- 25967271
TI  - Brief Report: Recent Infection, Sexually Transmitted Infections, and Transmission
      Clusters Frequently Observed Among Persons Newly Diagnosed With HIV in San
      Francisco.
AB  - There were 1311 newly diagnosed HIV cases in San Francisco between 2005 and 2011
      that were linked to care at publicly funded facilities and had viral sequences
      available for analysis. Of the 214 cases characterized as recently infected with
      HIV at the time of diagnosis, 25% had a recent sexually transmitted infection
      diagnosis (vs. 10% among longer-standing HIV infections, P < 0.001) and 57% were
      part of a phylogenetic transmission cluster (vs. 42% among longer-standing HIV
      infection, P < 0.001). The association observed between recent HIV infection and
      having a sexually transmitted infection diagnosis during the interval overlapping
      likely HIV acquisition points to potential opportunities to interrupt HIV
      transmission. 

PMID- 25967272
TI  - Changes to Initial Postexposure Prophylaxis Regimens Between the Emergency
      Department and Clinic.

PMID- 25967273
TI  - Recovery from severe H7N9 disease is associated with diverse response mechanisms
      dominated by CD8+ T cells.
AB  - The avian origin A/H7N9 influenza virus causes high admission rates (>99%) and
      mortality (>30%), with ultimately favourable outcomes ranging from rapid recovery
      to prolonged hospitalization. Using a multicolour assay for monitoring adaptive
      and innate immunity, here we dissect the kinetic emergence of different effector
      mechanisms across the spectrum of H7N9 disease and recovery. We find that a
      diversity of response mechanisms contribute to resolution and survival. Patients
      discharged within 2-3 weeks have early prominent H7N9-specific CD8(+) T-cell
      responses, while individuals with prolonged hospital stays have late recruitment
      of CD8(+)/CD4(+) T cells and antibodies simultaneously (recovery by week 4),
      augmented even later by prominent NK cell responses (recovery >30 days). In
      contrast, those who succumbed have minimal influenza-specific immunity and little
      evidence of T-cell activation. Our study illustrates the importance of robust
      CD8(+) T-cell memory for protection against severe influenza disease caused by
      newly emerging influenza A viruses. 

PMID- 25967275
TI  - Discovery of novel isatin-based sulfonamides with potent and selective inhibition
      of the tumor-associated carbonic anhydrase isoforms IX and XII.
AB  - A series of 2/3/4-[(2-oxo-1,2-dihydro-3H-indol-3
      ylidene)amino]benzenesulfonamides, obtained from substituted isatins and 2-, 3-
      or 4-aminobenzenesulfonamide, showed low nanomolar inhibitory activity against
      the tumor associated carbonic anhydrase (CA, EC 4.2.1.1) isoforms IX and XII -
      recently validated antitumor drug targets, being much less effective as
      inhibitors of the off-target cytosolic isoforms CA I and II. 

PMID- 25967274
TI  - Survival of patients with gastric lymphoma in Germany and in the United States.
AB  - BACKGROUND AND AIM: This study aims to examine survival for gastric lymphomas and
      its main subtypes, mucosa-associated lymphoid tissue lymphoma (MALT), and diffuse
      large B-cell lymphoma (DLBCL), in Germany and in the United States. METHODS: Data
      for patients diagnosed in 1997-2010 were used from 10 population-based German
      cancer registries and compared to the data from the US Surveillance, Epidemiology
      and End Results (SEER) 13 registries database. Patients age 15-74 diagnosed with
      gastric lymphomas were included in the analysis. Period analysis and modeled
      period analysis were used to estimate 5-year and 10-year relative survival (RS)
      in 2002-2010 and survival trends from 2002-2004 to 2008-2010. RESULTS: Overall,
      the database included 1534 and 2688 patients diagnosed with gastric lymphoma in
      1997-2010 in Germany and in the United States, respectively. Survival was
      substantially higher for MALT (5-year and 10-year RS: 89.0% and 80.9% in Germany,
      93.8% and 86.8% in the United States) than for DLBCL (67.5% and 59.2% in Germany,
      and 65.3% and 54.7% in the United States) in 2002-2010. Survival was slightly
      higher among female patients and decreased by age for gastric lymphomas combined
      and its main subtypes. A slight, nonsignificant, increase in the 5-year RS for
      gastric lymphomas combined was observed in Germany and the United States, with
      increases in 5-year RS between 2002-2004 and 2008-2010 from 77.1% to 81.0% and
      from 77.3% to 82.0%, respectively. Five-year RS of MALT exceeded 90% in 2008-2010
      in both countries. CONCLUSIONS: Five-year RS of MALT meanwhile exceeds 90% in
      both Germany and the United States, but DLBCL has remained below 70% in both
      countries.

PMID- 25967276
TI  - Electrodeposited Ni(x)Co(3-x)O4 nanostructured films as bifunctional oxygen
      electrocatalysts.
AB  - Nanostructured Ni(x)Co(3-x)O4 films serve as effective electrocatalysts for both
      the oxygen reduction and oxygen evolution reactions in alkaline electrolyte.

PMID- 25967277
TI  - GLP-2 as Beneficial Factor in the Glucose Homeostasis in Mice Fed a High Fat
      Diet.
AB  - Glucagon like peptide-2 (GLP-2) is a gastrointestinal hormone released in
      response to dietary nutrients, which acts through a specific receptor, the GLP-2
      receptor (GLP-2R). The physiological effects of GLP-2 are multiple, involving
      also the intestinal adaptation to high fat diet (HFD). In consideration of the
      well-known relationship between chronic HFD and impaired glucose metabolism, in
      the present study we examined if the blocking of the GLP-2 signaling by chronic
      treatment with the GLP-2R antagonist, GLP-2 (3-33), leads to functional
      consequences in the regulation of glucose metabolism in HFD-fed mice. Compared
      with animals fed standard diet (STD), mice at the 10th week of HFD showed
      hyperglycaemia, glucose intolerance, high plasma insulin level after glucose
      load, increased pancreas weight and beta cell expansion, but not insulin
      resistance. In HFD fed mice, GLP-2 (3-33) treatment for 4 weeks (from the 6th to
      the 10th week of diet) did not affect fasting glycaemia, but it significantly
      increased the glucose intolerance, both fasting and glucose-induced insulin
      levels, and reduced the sensitivity to insulin leading to insulin-resistance. In
      GLP-2 (3-33)-treated HFD mice pancreas was significantly heavier and displayed a
      significant increase in beta-cell mass in comparison with vehicle-treated HFD
      mice. In STD mice, the GLP-2 (3-33) treatment did not affect fasted or glucose
      stimulated glycemia, insulin, insulin sensitivity, pancreas weight and beta cell
      mass. The present study suggests that endogenous GLP-2 may act as a protective
      factor against the dysregulation of the glucose metabolism that occurs in HFD
      mice, because GLP-2 (3-33) worsens glucose metabolism disorders.

PMID- 25967279
TI  - Aggregation-induced preparation of ultrastable zinc sulfide colloidal nanospheres
      and their photocatalytic degradation of multiple organic dyes.
AB  - Monodispersed and ultrastable colloidal ZnS nanospheres (NPs) composed of tiny
      nanoparticles were successfully synthesized by using a limited ligand-induced in
      situ aggregation strategy. With such a strategy, the whole size as well as the
      particle size of those ZnS NPs could be tuned simultaneously by appropriately
      varying the reaction conditions. Three representative ZnS NP samples with
      different sphere sizes and particle sizes were thus obtained, which were all
      proven to possess rather large surface areas, robust structures and excellent
      colloidal stability. Furthermore, the photocatalytic activities of the as
      prepared ZnS NPs toward the photodegradation of eosin B, methylene blue and their
      binary mixture were explored respectively. An interesting size-dependent
      degradation performance associated with the ZnS NPs was observed in all the
      photodegradation cases. Finally, their degradation mechanism was fully elucidated
      according to the control experiments under different atmospheres in combination
      with the related energy level information. We believe that the control strategy
      for tuning the fine and whole structures of spherical nanostructures in a
      synergistic manner together with the structure-dependent photodegradation
      performance revealed herein will definitely benefit the fabrication of highly
      efficient photocatalysts as well as the nanocomplexes with hierarchical
      architectures. 

PMID- 25967278
TI  - Potential Years of Life Lost Due to Premature Mortality Among Treatment-Seeking
      Illicit Drug Users in Finland.
AB  - Premature death is a serious public health concern. The primary objective of this
      study was to examine premature deaths in terms of potential years of life lost
      (PYLL) in a cohort of 4817 treatment-seeking illicit drug users. Clients' data
      were linked to the Finnish national cause-of-death register and the follow-up
      period ranged from 31 January 1997 to 31 December 2010. PYLL before 70 years was
      calculated for all deaths and cause-specific deaths by gender. We observed 496
      deaths (417 males and 79 females) at the end of 2010. The mean age at death was
      33.8 years, 34.3 years for males (range 18-68) and 31.4 years for females (range
      16-53). Overall, 17,951 life years were lost; 14,898 among males and 3053 among
      females. The overall PYLL rate for males was more than twice that of females
      (513.0/1000 vs. 243.7/1000 person-years) but the mean PYLL was higher in females
      than males (38.6 vs. 35.7 years). Of the total PYLL, 34.8 % was due to accidental
      overdose, and 24.0 % to suicide. In both genders, accidental overdose and suicide
      were the two top-ranking causes of PYLL. Premature deaths among drug users are a
      potential loss to the society. Our findings suggest that measures targeting
      accidental overdose and suicide are top priorities for reducing preventable loss
      of life.

PMID- 25967281
TI  - Dronedarone and renal impairment: evaluation of Spanish postmarketing reports and
      review of literature.
AB  - BACKGROUND: Renal impairment associated with dronedarone use is hardly known. Our
      aim is to describe the characteristics of spontaneous reports involving renal
      adverse reactions with use of dronedarone. METHODS: In the Spanish
      Pharmacovigilance database, reports with renal reactions and dronedarone until
      May 2014 were retrieved and analyzed. Also, a review of case reports of renal
      failure and dronedarone was conducted in MEDLINE. RESULTS: Dronedarone was found
      as a suspected drug in 192 reports, 10 (5.2%) of these reports described renal
      reactions. Renal reactions appeared until 3 months after the onset of dronedarone
      treatment. In 5 out of 10 cases, dronedarone was withdrawn and the patient
      recovered. The Reporting Odds Ratio was 2.88 [95% CI 1.52 - 5.46; p < 0.05].
      Additionally, eight cases were found in the medical literature. In five of them,
      the patient outcome was described as recovered. One patient had to undergo
      hemodialysis for the treatment of their renal impairment. CONCLUSIONS: The effect
      of dronedarone on the renal function is supported by limited information;
      therefore, the cases from spontaneous reporting system and those from the medical
      literature could give relevant additional information. Our analysis shows a
      potential relationship between dronedarone use and renal impairment. Further
      studies are needed to confirm these findings.

PMID- 25967280
TI  - A histone modification identifies a DNA element controlling slo BK channel gene
      expression in muscle.
AB  - The slo gene encodes the BK-type Ca(2+)-activated K(+) channels. In Drosophila,
      expression of slo is induced by organic solvent sedation (benzyl alcohol and
      ethanol), and this increase in neural slo expression contributes to the
      production of functional behavioral tolerance (inducible resistance) to these
      drugs. Within the slo promoter region, we observed that benzyl alcohol sedation
      produces a localized spike of histone acetylation over a 65-nucleotide (65-n)
      conserved DNA element called 55b. Changes in histone acetylation are commonly the
      consequence of transcription factor activity, and previously, a localized histone
      acetylation spike was used to successfully map a DNA element involved in benzyl
      alcohol-induced slo expression. To determine whether the 55b element was also
      involved in benzyl alcohol-induced neural expression of slo, we deleted it from
      the endogenous slo gene by homologous recombination. Flies lacking the 55b
      element were normal with respect to basal and benzyl alcohol-induced neural slo
      expression, the capacity to acquire and maintain functional tolerance, their
      threshold for electrically-induced seizures, and most slo-related behaviors.
      Removal of the 55b element did however increase the level of basal expression
      from the muscle/tracheal cell-specific slo core promoter and produced a slight
      increase in overall locomotor activity. We conclude that the 55b element is
      involved in control of slo expression from the muscle and tracheal-cell promoter
      but is not involved in the production of functional benzyl alcohol tolerance. 

PMID- 25967282
TI  - micro RNA 172 (miR172) signals epidermal infection and is expressed in cells
      primed for bacterial invasion in Lotus japonicus roots and nodules.
AB  - Legumes interact with rhizobial bacteria to form nitrogen-fixing root nodules.
      Host signalling following mutual recognition ensures a specific response, but is
      only partially understood. Focusing on the stage of epidermal infection with
      Mesorhizobium loti, we analysed endogenous small RNAs (sRNAs) of the model legume
      Lotus japonicus to investigate their involvement in host response regulation. We
      used Illumina sequencing to annotate the L. japonicus sRNA-ome and isolate
      infection-responsive sRNAs, followed by candidate-based functional
      characterization. Sequences from four libraries revealed 219 novel L. japonicus
      micro RNAs (miRNAs) from 114 newly assigned families, and 76 infection-responsive
      sRNAs. Unlike infection-associated coding genes such as NODULE INCEPTION (NIN), a
      micro RNA 172 (miR172) isoform showed strong accumulation in dependency of both
      Nodulation (Nod) factor and compatible rhizobia. The genetics of miR172 induction
      support the existence of distinct epidermal and cortical signalling events.
      MIR172a promoter activity followed a previously unseen pattern preceding
      infection thread progression in epidermal and cortical cells. Nodule-associated
      miR172a expression was infection-independent, representing the second of two
      genetically separable activity waves. The combined data provide a valuable
      resource for further study, and identify miR172 as an sRNA marking successful
      epidermal infection. We show that miR172 acts upstream of several APETALA2-type
      (AP2) transcription factors, and suggest that it has a role in fine-tuning AP2
      levels during bacterial symbiosis. 

PMID- 25967283
TI  - Influence of dietary fatty acids on differentiation of human stromal vascular
      fraction preadipocytes.
AB  - Mediators such as cytokines, eicosanoids, nitric oxide and growth factors may
      regulate adipogenesis as well as inflammation. It is well documented that
      production of some form of eicosanoids activates lipid synthesis during
      adipogenesis but also contributes to the formation of factors maintaining low
      level systemic inflammation. Developing nutrients for reduction of adipogenesis
      and inflammation can enhance preventive efficacy of daily diet. This study
      examined the effects of free fatty acid influence on changes in lipid
      biosynthesis and corresponding gene expression during differentiation of human
      subcutaneous adipose tissue stromal vascular fraction (SVF) cells. Proadipogenic
      conditions promoted SVF cell differentiation and lipid droplet (LD) formation up
      to 15 days. This correlated with gene expression of adipocyte differentiation
      markers as well as inflammatory cytokines and their receptors. Addition of free
      fatty acids to differentiation medium increased their incorporation during the
      first period of differentiation (48 h). Presence of eicosanoid acid (EPA) during
      the initial period of differentiation by elevation of Perilipin 3 protein
      (TIP47), may be responsible for smaller LD formation. Presence of arachidonic
      acid (AA) tends to deposit lipids in large form of LDs. Prolongation of
      differentiation up to 15 days decreased AA or EPA in cellular lipids. PUFA
      through up-regulation of both phospholipase 2 and enzymes related to eicosanoid
      production influenced type and quantity of eicosanoids which regulated the extent
      of SVF cell differentiation. Formation of small LDs and reduction of pro
      inflammatory mediators in adipose tissue are the consequence of eicosanoid
      production with anti-inflammatory potential from EPA.

PMID- 25967284
TI  - Metals exposure and risk of small-for-gestational age birth in a Canadian birth
      cohort: The MIREC study.
AB  - BACKGROUND: Lead, mercury, cadmium and arsenic are some of the most common toxic
      metals to which Canadians are exposed. The effect of exposure to current low
      levels of toxic metals on fetal growth restriction is unknown. OBJECTIVE: The aim
      of this study was to examine relationships between exposure to lead, mercury,
      cadmium and arsenic during pregnancy, and risk of small for gestational age (SGA)
      birth. METHODS: Lead, mercury, cadmium and arsenic levels were measured in blood
      samples from the first and third trimesters in 1835 pregnant women from across
      Canada. Arsenic species in first trimester urine were also assessed. Relative
      risks and 95% confidence intervals were estimated using log binomial multivariate
      regression. Important covariates including maternal age, parity, pre-pregnancy
      BMI, and smoking, were considered in the analysis. An exploratory analysis was
      performed to examine potential effect modification of these relationships by
      single nucleotide polymorphisms (SNPs) in GSTP1 and GSTO1 genes. RESULTS: No
      association was found between blood lead, cadmium or arsenic and risk for SGA. We
      observed an increased risk for SGA for the highest compared to the lowest tertile
      of exposure for mercury (>1.6 ug/L, RR=1.56.; 95% CI=1.04-2.58) and arsenobetaine
      (>2.25 ug/L, RR=1.65; 95% CI=1.10-2.47) after adjustment for the effects of
      parity and smoking. A statistically significant interaction was observed in the
      relationship between dimethylarsinic acid (DMA) levels in urinary arsenic and SGA
      between strata of GSTO1 A104A (p for interaction=0.02). A marginally significant
      interaction was observed in the relationship between blood lead and SGA between
      strata of GSTP1 A114V (p for interaction=0.06). CONCLUSIONS: These results
      suggest a small increase in risk for SGA in infants born to women exposed to
      mercury and arsenic. Given the conflicting evidence in the literature this
      warrants further investigation in other pregnant populations.

PMID- 25967285
TI  - Golgi post-translational modifications and associated diseases.
AB  - For non specialists, Golgi is a very well known subcellular compartment involved
      in secretion and correct targeting of soluble and transmembrane proteins.
      Nevertheless, Golgi is also specifically involved in many different and diverse
      post-translational modifications. Through its diverse functions, Golgi is not
      only able to modify secreted and transmembrane proteins but also cytoplasmic
      proteins. The Golgi apparatus research field is so broad that an exhaustive
      review of this organelle is not doable here. The goal of this review is to cover
      the main post-translational modifications occurring at the Golgi level and
      present the identified associated diseases. 

PMID- 25967286
TI  - Safety, pharmacokinetics and efficacy findings in an open-label, single-arm study
      of weekly paclitaxel plus lapatinib as first-line therapy for Japanese women with
      HER2-positive metastatic breast cancer.
AB  - BACKGROUND: Lapatinib is the human epidermal growth factor receptor 2 (HER2)
      targeting agent approved globally for HER2-positive metastatic breast cancer
      (MBC). The efficacy, safety and pharmacokinetics (PK) of lapatinib combined with
      paclitaxel (L+P) were investigated in this study, to establish clear evidence
      regarding the combination in Japanese patients. METHODS: In this two-part, single
      arm, open-label study, the tolerability of L+P as first-line treatment in
      Japanese patients with HER2-positive MBC was evaluated in six patients in the
      first part, and the safety, efficacy and PK were evaluated in a further six
      patients (making a total of twelve patients) in the second part. Eligible women
      were enrolled and received lapatinib 1500 mg once daily and paclitaxel 80 mg/m(2)
      weekly for at least 6 cycles. RESULTS: The only dose-limiting toxicity reported
      was Grade 3 diarrhea in one patient. The systemic exposure to maximum plasma
      concentration and area under the plasma concentration curve (AUC) for lapatinib,
      as well as the AUC of paclitaxel, were increased when combined. The most common
      adverse events (AEs) related to the study treatment were alopecia, diarrhea and
      decreased hemoglobin. The majority of drug-related AEs were Grade 1 or 2. The
      median overall survival was 35.6 months (95 % confidence interval 23.9, not
      reached). The response rate and clinical benefit rate were both 83 % (95 %
      confidence interval 51.6, 97.9). CONCLUSIONS: The L+P treatment was well
      tolerated in Japanese patients with HER2-positive MBC. Although the PK profiles
      of lapatinib and paclitaxel influenced each other, the magnitudes were not
      greatly different from those in non-Japanese patients.

PMID- 25967287
TI  - Clinical features and risk factors of panitumumab-induced interstitial lung
      disease: a postmarketing all-case surveillance study.
AB  - BACKGROUND: Drug-induced interstitial lung disease (ILD) is one of the most
      serious adverse reactions associated with the molecularly targeted drugs.
      Panitumumab has been approved for advanced or recurrent colorectal cancer.
      Although there were no adverse reaction reports of ILD in panitumumab
      monotherapy, 4 cases in combination chemotherapy were reported prior to its
      approval in Japan in 2010. Several studies also reported that the incidence of
      drug-induced ILD was higher in Japan than in other countries. The clinical
      features of ILD and the associated risk factors therefore need investigation.
      METHODS: We analyzed the data from 3085 unresectable, advanced or recurrent
      colorectal cancer patients enrolled in a postmarketing all-case surveillance
      study of panitumumab in Japan. ILD case reports were assessed based on the
      clinical and radiologic findings by a committee of external experts. Multivariate
      analysis using Cox's hazard model identified the risk factors. RESULTS: ILD
      incidence (1.3 %) and mortality rates (51.3 %) were similar to those of patients
      receiving another anti-epidermal growth factor receptor (EGFR) monoclonal
      antibody in Japan. No specific onset timing was determined. Although panitumumab
      specific ILD findings were not observed in computed tomography images or clinical
      practice, panitumumab can induce ILD with diffuse alveolar damage, as do the
      other anti-EGFR targeting drugs. A history/complication of ILD, male sex, poor
      general condition, and 65 years or older were identified as ILD risk factors, and
      no history of previous drug treatment was an apparent risk factor. CONCLUSION:
      Panitumumab-induced ILD can occur at any time after initiation, and close and
      regular monitoring is needed.

PMID- 25967288
TI  - The Gut as a Source of Inflammation in Chronic Kidney Disease.
AB  - Chronic inflammation is a non-traditional risk factor for cardiovascular
      mortality in the chronic kidney disease (CKD) population. In recent years, the
      gastrointestinal tract has emerged as a major instigator of systemic inflammation
      in CKD. Postmortem studies previously discovered gut wall inflammation throughout
      the digestive tract in chronic dialysis patients. In CKD animals, colon wall
      inflammation is associated with breakdown of the epithelial tight junction
      barrier ('leaky gut') and translocation of bacterial DNA and endotoxin into the
      bloodstream. Gut bacterial DNA and endotoxin have also been detected in the serum
      from CKD and dialysis patients, whereby endotoxin levels increase with the CKD
      stage and correlate with the severity of systemic inflammation in the dialysis
      population. The CKD diet that is low in plant fiber and symbiotic organisms (in
      adherence with low potassium, low phosphorus intake) can alter the normal gut
      microbiome, leading to overgrowth of bacteria that produce uremic toxins such as
      cresyl and indoxyl molecules. The translocation of these toxins from the 'leaky
      gut' into the bloodstream further promotes systemic inflammation, adverse
      cardiovascular outcomes and CKD progression. Data are lacking on optimal fiber
      and yogurt consumption in CKD that would favor growth of a more symbiotic
      microbiome while avoiding potassium and phosphorus overload. Prebiotic and
      probiotic formulations have shown promise in small clinical trials, in terms of
      lowering serum levels of uremic toxins and improving quality of life. The
      evidence points to a strong relationship between intestinal inflammation and
      adverse outcomes in CKD, and more trials investigating gut-targeted therapeutics
      are needed.

PMID- 25967291
TI  - All-fiber 7 * 1 signal combiner for high power fiber lasers.
AB  - We present an all-fiber 7*1 signal combiner for high power fiber lasers. Through
      theoretical analysis, the fabrication method is confirmed and the taper length of
      the fiber bundle is chosen to be 1 cm to ensure a high transmission efficiency of
      the combiner. Based on the theoretical results, an all-fiber 7*1 signal combiner
      with high transmission efficiency is fabricated. A capillary with low refractive
      index is fused around the bundle of signal fibers to make an additional cladding
      layer. Then the fiber bundle is tapered to match the core of the output fiber and
      then spliced with the output fiber. The combiner is tested with a 500 W fiber
      laser and a temperature increase of 13 degrees C/kW without any active cooling is
      observed in the combiner. The power transmission efficiency is measured to be
      close to 99% for each input port and the beam quality M2 is around 10.

PMID- 25967292
TI  - Investigation of East Asian clouds with polarization light detection and ranging.
AB  - In this paper we present results of investigation of the main optical properties
      of East Asian clouds with a ground-based polarization lidar placed in Daejeon,
      Republic of Korea. Asian dust is located in elevated layers of the atmosphere in
      spring, travels long distances, and causes significant damage to ecology. We
      present backscattering matrices of clouds obtained from polarimetric remote
      measurements which comprise information on the scattering and absorption
      properties of cloud particles, their morphology, and spatial orientation. Theory
      of our applied lidar polarization experiment is presented in terms of the
      instrumental vectors of a transmitter and a receiver. Methods of solving linear
      and nonlinear systems of equations comprising echo signals are considered. Some
      numerical and measurement results are presented to illustrate the efficiency and
      versatility of the method of estimating the cloud parameters. 

PMID- 25967290
TI  - Local and systemic effect of transfection-reagent formulated DNA vectors on
      equine melanoma.
AB  - BACKGROUND: Equine melanoma has a high incidence in grey horses. Xenogenic DNA
      vaccination may represent a promising therapeutic approach against equine
      melanoma as it successfully induced an immunological response in other species
      suffering from melanoma and in healthy horses. In a clinical study, twenty-seven,
      grey, melanoma-bearing, horses were assigned to three groups (n = 9) and
      vaccinated on days 1, 22, and 78 with DNA vectors encoding for equine (eq) IL-12
      and IL-18 alone or in combination with either human glycoprotein (hgp) 100 or
      human tyrosinase (htyr). Horses were vaccinated intramuscularly, and one selected
      melanoma was locally treated by intradermal peritumoral injection. Prior to each
      injection and on day 120, the sizes of up to nine melanoma lesions per horse were
      measured by caliper and ultrasound. Specific serum antibodies against hgp100 and
      htyr were measured using cell based flow-cytometric assays. An Analysis of
      Variance (ANOVA) for repeated measurements was performed to identify
      statistically significant influences on the relative tumor volume. For post-hoc
      testing a Tukey-Kramer Multiple-Comparison Test was performed to compare the
      relative volumes on the different examination days. An ANOVA for repeated
      measurements was performed to analyse changes in body temperature over time. A
      one-way ANOVA was used to evaluate differences in body temperature between the
      groups. A p-value < 0.05 was considered significant for all statistical tests
      applied. RESULTS: In all groups, the relative tumor volume decreased
      significantly to 79.1 +/- 26.91% by day 120 (p < 0.0001, Tukey-Kramer Multiple
      Comparison Test). Affiliation to treatment group, local treatment and examination
      modality had no significant influence on the results (ANOVA for repeated
      measurements). Neither a cellular nor a humoral immune response directed against
      htyr or hgp100 was detected. Horses had an increased body temperature on the day
      after vaccination. CONCLUSIONS: This is the first clinical report on a systemic
      effect against equine melanoma following treatment with DNA vectors encoding
      eqIL12 and eqIL18 and formulated with a transfection reagent. Addition of DNA
      vectors encoding hgp100 respectively htyr did not potentiate this effect.

PMID- 25967293
TI  - Flow and thermal characteristics of high Reynolds number (2800-17,000) dye cell:
      simulation and experiment.
AB  - This paper presents computational and experimental studies on
      wavelength/frequency fluctuation characteristics of a high pulse repetition rate
      (18 kHz) dye laser pumped by a frequency-doubled Nd:YAG laser (532 nm). The
      temperature gradient in the dye solution is found to be responsible for
      wavelength fluctuations of the dye laser at low flow rates (2800<Re(d)<5600). The
      turbulence Reynolds number (ReT) and the range of eddy sizes present in the
      turbulent flow are found to be responsible for the fluctuations at high flow
      rates (8400<Re(d)<17,000). A new dimensionless parameter, dimensionless eddy size
      (l(+)), has been defined to correlate the range of eddy sizes with the
      experimentally observed wavelength fluctuations. It was found that fluctuations
      can be controlled by keeping ReT~10 and lmax(+)~1. The simulated result explains
      the experimental observation and provides a basis for optimizing the dye solution
      flow rate for high PRR pumping.

PMID- 25967294
TI  - Medium-high frequency FBG accelerometer with integrative matrix structure.
AB  - To meet the requirements for medium-high frequency vibration monitoring, a new
      type fiber Bragg grating (FBG) accelerometer with an integrative matrix structure
      is proposed. Two symmetrical flexible gemels are used as elastic elements, which
      drive respective inertial mass moving reversely when exciting vibration exists,
      leading to doubling the wavelength shift of the FBG. The mechanics model and a
      numerical method are presented in this paper, by which the influence of the
      structural parameters on the sensitivity and eigenfrequency is discussed.
      Sensitivity higher than 200  pm/g and an eigenfrequency larger than 3000 Hz can
      be realized separately, but both cannot be achieved simultaneously. Aiming for a
      broader measuring frequency range, a prototype accelerometer with an
      eigenfrequency near 3000 Hz is designed, and results from a shake table test are
      also demonstrated. 

PMID- 25967289
TI  - Cancer stem cells: a potential target for cancer therapy.
AB  - Current evidence indicates that a subpopulation of cancer cells, named cancer
      stem cells (CSCs) or tumor-initiating cells, are responsible for the initiation,
      growth, metastasis, therapy resistance and recurrence of cancers. CSCs share core
      regulatory pathways with normal stem cells; however, CSCs rely on distinct
      reprogrammed pathways to maintain stemness and to contribute to the progression
      of cancers. The specific targeting of CSCs, together with conventional
      chemotherapy or radiotherapy, may achieve stable remission or cure cancer.
      Therefore, the identification of CSCs and a better understanding of the complex
      characteristics of CSCs will provide invaluable diagnostic, therapeutic and
      prognostic targets for clinical application. In this review, we will introduce
      the dysregulated properties of CSCs in cancers and discuss the possible
      challenges in targeting CSCs for cancer treatment. 

PMID- 25967295
TI  - Compensation for straightness measurement systematic errors in six degree-of
      freedom motion error simultaneous measurement system.
AB  - The straightness measurement systematic errors induced by error crosstalk,
      fabrication and installation deviation of optical element, measurement
      sensitivity variation, and the Abbe error in six degree-of-freedom simultaneous
      measurement system are analyzed in detail in this paper. Models for compensating
      these systematic errors were established and verified through a series of
      comparison experiments with the Automated Precision Inc. (API) 5D measurement
      system, and the experimental results showed that the maximum deviation in
      straightness error measurement could be reduced from 6.4 to 0.9 MUm in the x
      direction, and 8.8 to 0.8 MUm in the y-direction, after the compensation. 

PMID- 25967296
TI  - Influence of index matching on AA/PVA photopolymers for low spatial frequency
      recording.
AB  - Photopolymers present appealing optical properties for holographic and
      diffractive applications. They enable modulation of the electrical permittivity
      and thickness and are self-processing, and layers with a wide range of
      thicknesses and properties can be fabricated on demand. In order to obtain a
      complete characterization of the material, low spatial frequency analysis has
      become a fundamental tool because the motion of the components inside of the
      material can be measured. We propose to use an index matching component to carry
      out a complete characterization and to differentiate the "apparent" and the real
      monomer diffusion. We also have quantified the minimum thickness to obtain the
      phase modulation of 2pi required for the fabrication of many diffractive elements
      such as lenses, axicons, or blazed gratings. Finally, we have studied the
      influence of the thermal effects in the thickness variations. 

PMID- 25967297
TI  - Design optimization of two concatenated long period waveguide grating devices for
      an application specific target spectrum.
AB  - We propose a global optimization method to optimize the parameters of two
      concatenated long period waveguide gratings (LPWGs) for generating a desired
      target spectrum. The design consists of two concatenated LPWGs with different
      grating periods inscribed in the guiding films of a four-layer planar waveguide
      with finite over cladding. We have used the transfer matrix method to compute the
      modes of the structure and the coupled mode theory to compute the spectrum of the
      device. The adaptive particle swarm optimization method has been used to optimize
      the parameters of LPWGs to generate symmetric as well as asymmetric target
      spectra. Two concatenated gratings of different lengths and periods have been
      used to generate the target spectra. To demonstrate the method of optimization we
      have designed a variety of wavelength filters including a rectangular shape
      rejection band filter, asymmetric band rejection filters, band rejection filters
      for flattening the amplified spontaneous emission (ASE) spectrum of an erbium
      doped fiber amplifier (EDFA), and a gain equalization filter for an erbium doped
      waveguide amplifier (EDWA) in the C-band. Seven parameters of the proposed LPWG
      structure have been optimized to achieve the desired spectra. We have obtained an
      ASE flattening with +/-0.8  dB peak-to-peak ripple in case of the EDFA and gain
      flattening with +/-0.4  dB peak-to-peak ripple in case of an EDWA. The study
      would be useful in the design of wavelength filters for specific applications. 

PMID- 25967298
TI  - Practical technique for improving all-fiber coherent combination of multistage
      high-power ytterbium fiber amplifiers.
AB  - We demonstrate coherent combination of two high-gain and high-power single-mode 1
      MUm fiber amplifiers via direct pump current modulation. Each all-fiber amplifier
      channel, which is built as a master oscillator-multiple amplifier architecture,
      can operate either continuous waves or 4 ns, 1 MHz pulses with average power of
      50 W and more than 55 dB gain. These two amplifiers are coherently combined by
      modulating the pump currents of the preamplifiers in a multidither arrangement.
      The key feature of the scaling scheme is the insertion of a designated second
      stage preamplifier between the first stage preamplifier and the final power
      amplifier stage, so as to improve the coherency and to minimize the gain
      variation of the preamplifier to the power amplifier. Otherwise, overall phase
      control of the fiber amplifiers with this method is not possible at such a high
      power level. 

PMID- 25967299
TI  - Bandwidth efficient coherent lidar based on phase-diversity detection.
AB  - Bandwidth efficient coherent lidar based on phase-diversity detection is reported
      for the first time, to the best of our knowledge, which allows the doubling of
      bandwidth efficiency through the simultaneous utilization of the in-phase (I) and
      quadrature (Q) components. By maintaining RF phase continuity between linearly
      frequency-chirped I and Q components through digital signal processing, the range
      resolution of the lidar system can be improved. 

PMID- 25967300
TI  - Correcting temperature dependence in miniature spectrometers used in cold polar
      environments.
AB  - Measurement biases arising from changes in temperature can be a major concern
      when using miniature spectrometers in extreme environments, particularly when
      temperature stabilization approaches are not feasible. Here, temperature-related
      biases of a low-power field spectrometry system comprised of a CMOS miniature
      monolithic spectrometer module and custom driver electronics were examined
      between -40 degrees C and +25.6 degrees C, well below the stated operating range
      of this particular spectrometer. Using these observations, a predictive model was
      developed to estimate the dark output of the spectrometry system within this
      extended operating range. This information was used to correct the signal at any
      measured integration time and temperature to that which would be measured at a
      reference integration time and temperature. This approach provides a general
      framework for assessing the temperature dependence of monolithic spectrometers
      whose field use will occur at temperatures outside of the range examined by the
      manufacturer. 

PMID- 25967301
TI  - High-efficiency receiver architecture for resonance-fluorescence and Doppler
      lidars.
AB  - A high-efficiency lidar receiver architecture that emphasizes boosting the
      receiver collection efficiency of resonance-fluorescence and Doppler lidars has
      opened up new avenues of study for the mesosphere and lower thermosphere-extended
      (MLT-X) at sites in Boulder, Colorado, USA, and Cerro Pachon, Chile. Described in
      this work are in-depth considerations in the design, construction, and alignment
      of Na Doppler lidar receivers that have yielded signal levels typically 5-10
      times higher per power-aperture product than any demonstrated in the literature,
      to these authors' knowledge, making studies of fine-scale MLT turbulence and
      tenuous thermospheric layers in Na possible with temperature and vertical wind
      capability for the first time. A lowering of the detection threshold by higher
      receiver collection efficiency at Cerro Pachon has enabled this Na Doppler lidar
      to extend its measurement range far higher into the thermosphere, to regions with
      Na density less than 3  cm(-3). With renewed interest in the MLT-X region
      prompted by recent lidar discoveries of Fe in the thermosphere reaching 170 km at
      McMurdo, Antarctica, the receiver optimizations we have made now enable
      addressing an important need in the community. In addition, the higher spatial
      and temporal resolutions afforded by high signal-to-noise ratio, down to
      resolutions of ~20  s and ~20  m, promise to make the first direct measurements
      of eddy flux in the mesopause region possible. Results from deployment of
      optimized receivers at the Table Mountain Lidar Observatory in Boulder, the Andes
      Lidar Observatory at Cerro Pachon, and the Arecibo Observatory in Puerto Rico are
      presented to demonstrate the power and portability of our methods that are
      readily applicable to other lidar varieties, including, but not limited to, the
      newly developed Fe Doppler lidar and recently upgraded K Doppler lidar.

PMID- 25967302
TI  - Multi-point vibrometer based on high-speed digital in-line holography.
AB  - This paper describes a digital holographic setup based on in-line holography and
      a high-speed recording to get a multipoint vibrometer. The use of a high-speed
      sensor leads to specificities that enable the in-line configuration to be used.
      The case of transient vibrations is investigated through a full simulation of the
      holographic process. The simulation shows that the first instants are critical
      since distortion may occur, resulting in errors in the phase measurement.
      Experimental results are provided by exciting an aluminum beam with a transient
      signal. A comparison with the velocity measured by a pointwise vibrometer is
      provided. Frequency response functions are extracted and the experimental results
      confirm the ability of the method to provide full-field contactless measurements
      at the high-speed time scale evolution of the vibration. 

PMID- 25967303
TI  - Phase retrieval encryption in an enhanced optical interference by key phase
      constraint.
AB  - In this paper, we demonstrate a security system by using optical interference and
      phase retrieval algorithm (PRA) techniques. The modified PRA is proposed to
      encode the target image into random phase distribution. Optical and digital
      methods can be used for decryption. By using this method, silhouette elimination
      is realized. In addition, due to this simplified system design, the iterative
      rate is improved and the optical decryption realization is easier. Validity and
      performance of the proposed system are demonstrated by means of numerical
      simulations. The system encryption capacity as to both binary and gray images is
      numerically investigated. Then, the decryption procedure is demonstrated by
      optical experiment means and the decryption result is given. 

PMID- 25967304
TI  - Multiple-image authentication with a cascaded multilevel architecture based on
      amplitude field random sampling and phase information multiplexing.
AB  - A multiple-image authentication method with a cascaded multilevel architecture in
      the Fresnel domain is proposed, in which a synthetic encoded complex amplitude is
      first fabricated, and its real amplitude component is generated by iterative
      amplitude encoding, random sampling, and space multiplexing for the low-level
      certification images, while the phase component of the synthetic encoded complex
      amplitude is constructed by iterative phase information encoding and multiplexing
      for the high-level certification images. Then the synthetic encoded complex
      amplitude is iteratively encoded into two phase-type ciphertexts located in two
      different transform planes. During high-level authentication, when the two phase
      type ciphertexts and the high-level decryption key are presented to the system
      and then the Fresnel transform is carried out, a meaningful image with good
      quality and a high correlation coefficient with the original certification image
      can be recovered in the output plane. Similar to the procedure of high-level
      authentication, in the case of low-level authentication with the aid of a low
      level decryption key, no significant or meaningful information is retrieved, but
      it can result in a remarkable peak output in the nonlinear correlation
      coefficient of the output image and the corresponding original certification
      image. Therefore, the method realizes different levels of accessibility to the
      original certification image for different authority levels with the same
      cascaded multilevel architecture. 

PMID- 25967306
TI  - Normalized pulsed energy thresholding in a nonlinear optical loop mirror.
AB  - We demonstrate for the first time, to the best of our knowledge, that a Sagnac
      interferometer can threshold the energies of pulses. Pulses below a given
      threshold T are suppressed, while those above this threshold are normalized. The
      device contains an in-loop tunable isolator and 10.4 m of a highly doped silica
      fiber. We derive an analytical model of the nonlinear optical loop mirror's pulse
      energy transfer function and show that its energy transfer function approximates
      a step function for very high phase shifts (>pi). We reveal some limitations of
      this approach, showing that a step-function transfer function necessarily results
      in pulse distortion in fast, nonresonant all-optical devices. 

PMID- 25967307
TI  - High-power passively Q-switched Yb:YCa4O(BO3)3 laser with a GaAs crystal plate as
      saturable absorber.
AB  - We report on efficient high-power passively Q-switched operation of a
      Yb:YCa4O(BO3)3 laser with a GaAs crystal plate acting as the saturable absorber.
      An average output power of 5.7 W at 1032 nm is generated at a pulse repetition
      rate of 166.7 kHz when the incident pump power is 26.8 W, with a slope efficiency
      determined to be 24.5%. The averaged pulse energy achieved is roughly 30 MUJ and
      is increased to about 40 MUJ when the output coupling used changes from 30% to
      50%, while the shortest pulse width is measured to be 153 ns.

PMID- 25967308
TI  - Simultaneous measurement of pressure and temperature using dual-path distributed
      Brillouin sensor.
AB  - A sensing technique called a dual-path distributed Brillouin sensor (D-DBS) is
      proposed for simultaneous measurement of pressure and temperature. The D-DBS
      consists of a pair of sensing fibers, which are designed with different pressure
      and temperature coefficients of Brillouin frequency shift (BFS) by taking
      advantage of different fiber coatings. The highlight of this technique is to
      resolve the problem of the pressure-temperature cross sensitivity of the BFS
      within the optical fibers. The validation experiment shows satisfactory results,
      and it is indicated theoretically that the expected precisions of pressure and
      temperature are less than 0.25 MPa and 0.28 degrees C, respectively. 

PMID- 25967309
TI  - Balancing polarization aberrations in crossed fold mirrors.
AB  - The polarization aberrations of a fold mirror can be compensated by orienting a
      second fold mirror's p-polarization with the first mirror's s-polarization. This
      crossed-mirror configuration compensates the polarization for a single angle to
      zero and leaves a linear variation of diattenuation and retardance for a
      spherical wavefront. Two sets of crossed fold mirrors when properly oriented
      compensate the remaining linear variation and leave a much reduced quadratic
      variation in a large compensated field of view. 

PMID- 25967310
TI  - Binocular vision measurement using Dammann grating.
AB  - In this paper, we propose a novel three-dimensional (3D) profilometry using a
      binocular camera and a 64 * 64 Dammann grating for generation of a regular square
      laser array. A new constraint called a "ray constraint," taking advantage of the
      splitting characteristic of Dammann grating, is proposed for binocular matching.
      Binocular matching is realized by using ray constraint and precalibration of a
      laser array. Point clouds without outliers are obtained with binocular matching
      results according to triangulation. The experimental apparatus weighs less than
      170 g with a width of less than 14 cm. We used this apparatus to scan a statue of
      Apollo under indoor illumination (at 450 lux). Its 3D model with complex profile
      was reconstructed by more than 150,000 points. This 3D profilometry has
      advantages of low cost, low power, and small size and should be useful for
      practical applications. 

PMID- 25967311
TI  - Optical design of a light-emitting diode lamp for a maritime lighthouse.
AB  - Traffic signaling is an emerging field for light-emitting diode (LED)
      applications. This sustainable power-saving illumination technology can be used
      in maritime signaling thanks to the recently updated norms, where the possibility
      to utilize LED sources is explicitly cited, and to the availability of high-power
      white LEDs that, combined with suitable lenses, permit us to obtain well
      collimated beams. This paper describes the optical design of a LED-based lamp
      that can replace a traditional lamp in an authentic marine lighthouse. This
      source recombines multiple separated LEDs realizing a quasi-punctual localized
      source. Advantages can be lower energy consumption, higher efficiency, longer
      life, fewer faults, slower aging, and minor maintenance costs. The proposed LED
      source allows us to keep and to utilize the old Fresnel lenses of the lighthouse,
      which very often have historical value. 

PMID- 25967312
TI  - Gain and bandwidth investigation in a near-zero ultra-flat dispersion PCF for
      optical parametric amplification around the communication wavelength.
AB  - In this work, we explore the fiber optical parametric amplifiers (FOPAs) gain and
      bandwidth spectra of near-zero ultra-flattened photonic crystal fibers (PCFs)
      around the communication wavelength. The parametric gain and spectral bandwidth
      have been explored for all the three zero-dispersion wavelengths (ZDWs) of the
      near-zero ultra-flat fiber. Our numerical analysis establishes a dispersion
      profile with D=0+/-0.35  ps/nm/km for a bandwidth of 440 nm around the
      communication wavelength to fully exploit the four-wave mixing effect with three
      ZDWs for broadband applications. It has been observed that the broader gain
      spectrum of FOPAs can be achieved with the near-zero and ultra-flattened
      dispersion curve with proper tuning of the pumping condition. A broader bandwidth
      with sufficient peak gain value has been achieved with small negative anomalous
      dispersion (beta2<=0) and positive value of fourth-order dispersion parameter
      (+ve  beta4) around the pumping wavelength. Wider bandwidth of the parametric
      amplifier has been observed around the second ZDW with a negative slope of the
      dispersion curve. A total bandwidth ~520  nm could be achieved with the ultra
      flat dispersion nature of the optimized PCF. The design methodology of achieving
      wider gain by tuning the pumping wavelength for favorable higher-order dispersion
      parameters would be very useful for future dispersion engineered devices.

PMID- 25967313
TI  - Multiple-image encryption based on triple interferences for flexibly decrypting
      high-quality images.
AB  - We propose a multiple-image encryption (MIE) scheme based on triple interferences
      for flexibly decrypting high-quality images. Each image is discretionarily
      deciphered without decrypting a series of other images earlier. Since it does not
      involve any cascaded encryption orders, the image can be decrypted flexibly by
      using the novel method. Computer simulation demonstrated that the proposed
      method's running time is less than approximately 1/4 that of the previous similar
      MIE method. Moreover, the decrypted image is perfectly correlated with the
      original image, and due to many phase functions serving as decryption keys, this
      method is more secure and robust. 

PMID- 25967314
TI  - Compressive sensing for direct millimeter-wave holographic imaging.
AB  - Direct millimeter-wave (MMW) holographic imaging, which provides both the
      amplitude and phase information by using the heterodyne mixing technique, is
      considered a powerful tool for personnel security surveillance. However, MWW
      imaging systems usually suffer from the problem of high cost or relatively long
      data acquisition periods for array or single-pixel systems. In this paper,
      compressive sensing (CS), which aims at sparse sampling, is extended to direct
      MMW holographic imaging for reducing the number of antenna units or the data
      acquisition time. First, following the scalar diffraction theory, an exact
      derivation of the direct MMW holographic reconstruction is presented. Then, CS
      reconstruction strategies for complex-valued MMW images are introduced based on
      the derived reconstruction formula. To pursue the applicability for near-field
      MMW imaging and more complicated imaging targets, three sparsity bases, including
      total variance, wavelet, and curvelet, are evaluated for the CS reconstruction of
      MMW images. We also discuss different sampling patterns for single-pixel, linear
      array and two-dimensional array MMW imaging systems. Both simulations and
      experiments demonstrate the feasibility of recovering MMW images from
      measurements at 1/2 or even 1/4 of the Nyquist rate. 

PMID- 25967315
TI  - Near-IR nonlinear optical filter for optical communication window.
AB  - We report on a high performance nonlinear optical filter for the
      telecommunication window that employs detonation nanodiamonds (NDs). The
      nanosecond Z-scan experiments revealed that the heavy water ND suspensions enable
      strong optical limiting in the wavelength range of 1400-1675 nm. We observed an
      enhancement of the optical limiting performance in the blue part of the
      communication window. In particular, at the wavelength of 1400 nm the
      transmittance of the 2 mm thick sample with 4.5 wt. % ND concentration is
      suppressed by 45% for the input fluence of 3.8  J/cm(2). The proposed nonlinear
      optical filter employs the phenomena of the nonlinear absorption and the
      nonlinear light scattering in ND suspensions.

PMID- 25967316
TI  - Resolution enhancement in active underwater polarization imaging with modulation
      transfer function analysis.
AB  - Active polarization imaging technology is a convenient and promising method for
      imaging in a scattering medium such as fog and turbid water. However, few studies
      have investigated the influence of polarization on the resolution in underwater
      imaging. This paper reports on the effects of polarization detection on the
      resolution of underwater imaging by using active polarization imaging technology.
      An experimental system is designed to determine the influence under various
      polarization and water conditions. The modulation transfer function is introduced
      to estimate the resolution variations at different spatial frequencies. Results
      show that orthogonal detection supplies the best resolution compared with other
      polarization directions in the turbid water. The performance of the circular
      polarization method is better than the linear process. However, if the light
      propagates under low scattering conditions, such as imaging in clean water or at
      small optical thickness, the resolution enhancement is not sensitive to the
      polarization angles. 

PMID- 25967317
TI  - Liquid crystal microlens arrays recorded by polarization holography.
AB  - We report the characterization of diffractive microlens arrays (MAs) using a
      polarization holographic approach assisted by a spatial light modulator (SLM), in
      a nematic liquid crystal (NLC) cell. The MAs were recorded in the photoaligning
      substrates of the cell and then replicated in the NLC bulk, through the surface
      interactions. The transparency of the NLC on a wide range of wavelengths and the
      ability to tune its optical birefringence, through an external voltage, allowed
      us to create MAs with high efficiency. We have presented the results obtained for
      diverse MAs configurations, composed by spherical and cylindrical microlenses and
      characterized by different focal lengths. The efficiency reaches a value of 90%,
      at a wavelength of 633 nm. 

PMID- 25967318
TI  - Chromatic characterization of ion-exchanged glass binary phase plates for mode
      division multiplexing.
AB  - Mode-division multiplexing (MDM) in few-mode fibers is regarded as a promising
      candidate to increase optical network capacity. A fundamental element for MDM is
      a modal transformer to LP modes which can be implemented in a free-space basis by
      using multiregion phase plates, that is, LP plates. Likewise, several wavelengths
      have to be used due to wavelength multiplexing purposes, optical amplification
      tasks, and so on. In this work we show that efficient monolithic binary phase
      plates for different wavelengths can be fabricated by ion-exchange in glass and
      used for MDM tasks. We introduce an optical characterization method of the
      chromatic properties of such phase plates which combines the inverse Wentzel
      Kramers-Brillouin (IWKB) together with Mach-Zehnder and Michelson-based
      interferometric techniques. The interferometric method provides a measurement of
      the phase step for several wavelengths, which characterizes the chromatic
      properties of the phase plate. Consequently, it is shown that the IWKB method
      allows us to design and characterize the phase plates in an easy and fast way. 

PMID- 25967319
TI  - Development of a space-borne spectrometer to monitor atmospheric ozone.
AB  - A new compact satellite spectrometer dedicated to monitoring terrestrial
      atmospheric ozone (ozonometer) is in preparation for the Russian Geophysics
      Program. Four instruments at four satellites (Ionosphere) are intended to monitor
      the total ozone content by measuring spectra of scattered solar radiation in
      nadir. The spectrometer is based on the Rowland scheme with a concave holographic
      diffraction grating. It covers the near UV and visible range of the spectrum, 300
      500 nm, with a spectral resolution of ~0.3  nm. At present, a qualification model
      has been manufactured and tested. We introduce the description of the instrument
      and the results of laboratory and ground-based atmospheric calibrations. The
      ozone amount retrieved from atmospheric measurements using the differential
      optical absorption spectroscopy (DOAS) method is in good agreement with that
      measured by the collocated Brewer spectrophotometer and ozone monitoring
      instrument on board the Aura satellite. 

PMID- 25967320
TI  - Effects of material parameters upon the dipolar scattering characteristics of
      uncoated or coated sphere.
AB  - An analytical theory for the dipolar scattering characteristics of uncoated or
      coated sphere with different materials is presented. These materials are
      magnetodielectric, single negative, single near zero, and double near zero (DNZ)
      materials. It is shown that an uncoated magnetodielectric sphere has nearly
      identical E- and H-plane scattered intensities. It is further observed that for
      an epsilon near zero (ENZ) sphere, the intensity of scattered field in the E
      plane is nearly isotropic. For a coated sphere, it is shown that a
      magnetodielectric sphere coated with ENZ and mu near zero materials have nearly
      identical E-plane scattered intensities in the forward and backward scattering
      (BS) directions. Likewise, it is also shown that a finite sized magnetodielectric
      sphere coated with a DNZ layer can be made hidden to the incoming wave in the BS
      direction. 

PMID- 25967321
TI  - Effects of repetitive pulsing on multi-kHz planar laser-induced incandescence
      imaging in laminar and turbulent flames.
AB  - Planar laser-induced incandescence (LII) imaging is reported at repetition rates
      up to 100 kHz using a burst-mode laser system to enable studies of soot formation
      dynamics in highly turbulent flames. To quantify the accuracy and uncertainty of
      relative soot volume fraction measurements, the temporal evolution of the LII
      field in laminar and turbulent flames is examined at various laser operating
      conditions. Under high-speed repetitive probing, it is found that LII signals are
      sensitive to changes in soot physical characteristics when operating at high
      laser fluences within the soot vaporization regime. For these laser conditions,
      strong planar LII signals are observed at measurement rates up to 100 kHz but are
      primarily useful for qualitative tracking of soot structure dynamics. However,
      LII signals collected at lower fluences allow sequential planar measurements of
      the relative soot volume fraction with a sufficient signal-to-noise ratio at
      repetition rates of 10-50 kHz. Guidelines for identifying and avoiding the onset
      of repetitive probe effects in the LII signals are discussed, along with other
      potential sources of measurement error and uncertainty. 

PMID- 25967322
TI  - Mid-infrared emission and Raman spectra analysis of Er(3+)-doped
      oxyfluorotellurite glasses.
AB  - This paper reports on the spectroscopic and structural properties in Er(3+)-doped
      oxyfluorotellurite glasses. The compositional variation accounts for the
      evolutions of Raman spectra, Judd-Ofelt parameters, radiative properties, and
      fluorescent emission. It is found that, when maximum phonon energy changes
      slightly, phonon density plays a crucial role in quenching the 2.7 MUm emission
      generated by the Er(3+):(4)I11/2->(4)I13/2 transition. The comparative low phonon
      density contributes strong 2.7 MUm emission intensity. The high branching ratio
      (18.63%) and large emission cross section (0.95*10(-20)  cm(2)) demonstrate that
      oxyfluorotellurite glass contained with 50 mol.% TeO2 has potential application
      in the mid-infrared region laser.

PMID- 25967323
TI  - Compact stabilized semiconductor laser for frequency metrology.
AB  - We report on the development of a frequency modulatable 795 nm semiconductor
      laser based on self-injection locking to a high-quality-factor whispering-gallery
      mode microresonator. The laser is characterized by residual amplitude modulation
      below -80  dB and frequency noise better than 300  Hz/Hz(1/2) at offset
      frequencies ranging from 100 Hz to 10 MHz. The frequency modulation speed and
      span of the laser exceed 1 MHz and 4 GHz, respectively. Locking of the laser to
      the Doppler-free saturated absorption resonance of the (87)Rb D1 line is
      demonstrated and relative frequency stability better than 10(-12) is measured for
      integration time spanning from 1 s to 1 day. The architecture demonstrated in
      this study is suitable for the realization of frequency modulatable lasers at any
      wavelength.

PMID- 25967324
TI  - Reflective liquid crystal display for better productivity.
AB  - Most reflective LCDs so far proposed require a very thin cell gap of
      approximately 1.5 MUm to satisfy the quarter-wave retardation condition when used
      with a half-wave retardation film to obtain an acceptable broadband performance
      over the entire visible range. On the other hand, the inevitable difficulty
      associated with precise manufacturing of thin cell gap devices is likely to
      deteriorate the yield, thereby increasing the production cost. This paper
      proposes a reflective LCD with a larger cell thickness to achieve better
      productivity. The proposed reflective LCD consists of a tactically arranged stack
      of a half-wave retardation film, a quarter-wave retardation film, and a liquid
      crystal (LC) layer whose optical performance has been confirmed both by
      simulation and experiment. The optimal optical configuration to obtain an
      excellent dark state in the visible range was determined by the Mueller matrices
      calculus as applied to each optical component. The simulated and experimental
      results showed that the proposed reflective LC structure has excellent electro
      optical properties and is expected to be useful for the next generation LCD
      industry. 

PMID- 25967325
TI  - Effect of etching morphology of artificial defect on laser-induced damage
      properties under 355  nm laser irradiation.
AB  - Structural defects and absorptive impurities generated in the process of grinding
      and polishing optical substrates before coating significantly lower the
      resistance of optical elements to laser. Thus, artificial defects that contain
      indentations and absorptive particles are fabricated in this study. Chemical
      etching is used to examine the morphology and depth of artificial defects with
      different sizes and types under various etching times. Moreover, the transverse
      and longitudinal sizes, as well as the morphology, of defects are determined to
      analyze the damage properties of artificial defects under 355 nm of laser
      irradiation. Finally, the differences in the artificial defects induced by
      various materials are discussed along with their influences on damage properties.

PMID- 25967326
TI  - Context guided belief propagation for remote sensing image classification.
AB  - We propose a context guided belief propagation (BP) algorithm to perform high
      spatial resolution multispectral imagery (HSRMI) classification efficiently
      utilizing superpixel representation. One important characteristic of HSRMI is
      that different land cover objects possess a similar spectral property. This
      property is exploited to speed up the standard BP (SBP) in the classification
      process. Specifically, we leverage this property of HSRMI as context information
      to guide messages passing in SBP. Furthermore, the spectral and structural
      features extracted at the superpixel level are fed into a Markov random field
      framework to address the challenge of low interclass variation in HSRMI
      classification by minimizing the discrete energy through context guided BP (CBP).
      Experiments show that the proposed CBP is significantly faster than the SBP while
      retaining similar performance as compared with SBP. Compared to the baseline
      methods, higher classification accuracy is achieved by the proposed CBP when the
      context information is used with both spectral and structural features. 

PMID- 25967327
TI  - Time delay compensation method for tip-tilt control in adaptive optics system.
AB  - The time delay engendered by wavefront sampling and data processing inevitability
      exists in almost all the wavefront sensor (WFS) based adaptive optics (AO)
      systems. Also, when WFS is used for tip-tilt aberration detection, the time delay
      significantly reduces the tip-tilt correction performance of the AO system. In
      this paper, we focus on researching time delay in a tip-tilt (TT) control system
      and introduce a predicted signal compensation method (PSCM) to compensate the
      time delay by modifying the WFS detected signals. Based on a precise model of a
      TT dynamic control system, the detection delay of TT corrections included in a
      WFS detected signal can be compensated. Experiments are conducted in the lab: the
      pure integrator (I), proportional and integral (PI) wavefront TT controllers, and
      these controllers with PSCM are compared to test the efficiency of the PSCM for
      TT corrections. For the PI controller, the rejection bandwidth increases from 52
      to 62 Hz by using PCSM; meanwhile, the open-loop phase margin increases from 45
      to 60 deg. In addition, astronomical observation results are also given based on
      the PI wavefront TT controller. The PSCM improves the Strehl ratio by a factor of
      1.3. The new method is proven to improve the AO system closed-loop performance
      not only for increasing the closed-loop rejection bandwidth but also in favor of
      the error attenuation at low frequency. Furthermore, the method does not
      introduce more noise to the system. 

PMID- 25967328
TI  - 7.6  W 1342  nm passively mode-locked picosecond composite Nd:YVO4/YVO4 laser
      with a semiconductor saturable absorber mirror.
AB  - A high average power 1342 nm passively CW mode-locked picoseconds (ps) composite
      Nd:YVO4 laser was demonstrated with a semiconductor saturable absorber mirror
      (SESAM). The oscillator cavity was carefully designed to optimize the laser beam
      radii in the crystal and on the SESAM. The combination of composite bonded laser
      crystal, direct pumping, and dual end-pumped configuration was adopted to reduce
      the thermal effect and produce high output power with high beam quality. A
      maximum average output power of 7.63 W was obtained with a repetition rate of 77
      MHz and a pulse duration of 24.2 ps under an absorbed pump power of 38.6 W,
      corresponding to an optical-optical efficiency of 19.7% and a slope efficiency of
      25.9%, respectively. The beam quality factor M(2) was measured to be 1.49.

PMID- 25967329
TI  - Three-dimensional displacement measurement from phase signals embedded in a frame
      in digital holographic interferometry.
AB  - A novel technique is proposed for the simultaneous measurement of all three
      components of displacement from a single recording of the interference field in
      digital holographic interferometry. The interference field is divided into a
      number of rectangular segments, and in each of these segments, the interference
      field is represented as a multicomponent low-order two-dimensional (2D)
      polynomial phase signal. 2D-product high-order ambiguity function based analysis
      is applied to obtain an accurate estimation of the 2D polynomial coefficients.
      These coefficients are further used to compute the interference phases. The
      simulation and experimental results show the robustness of the proposed method to
      noise and its effectiveness in multiple phase estimation. 

PMID- 25967330
TI  - Numerical generation of laser-resonance phase noise for optical communication
      simulators.
AB  - We generate random numerical waveforms that mimic laser phase noise incorporating
      laser-resonance enhanced phase noise. The phase noise waveforms are employed in
      system simulators to estimate the resulting bit error rate penalties for
      differential quadrature phase shift keying signals. The results show that
      baudrate dependence of the bit error rate performance arises from laser-resonance
      phase noise. In addition, we show with supporting experimental results that the
      laser-resonance phase noise on the pumps in four-wave-mixing-based wavelength
      converters is responsible for large bit error rate floors. 

PMID- 25967331
TI  - Regions of spreading of Gaussian array beams propagating through oceanic
      turbulence.
AB  - The spreading of Gaussian array beams for two types of beam combination
      propagating through turbulent ocean is investigated. Analytical formulas for the
      Rayleigh range zR and turbulence distances zT and zTT are derived. Numerical
      results show that the spreading regions are influenced by the oceanic turbulence
      parameters and the source parameters. Moreover, the Rayleigh range of the
      coherent combination case tends to be more sensitive to parameters of the source
      and oceanic turbulence than that for the incoherent combination one, while in the
      case of turbulence distances, it is the reverse.

PMID- 25967333
TI  - Slim near-eye display using pinhole aperture arrays.
AB  - We report a new technique for building a wide-angle, lightweight, thin-form
      factor, cost-effective, easy-to-manufacture near-eye head-mounted display (HMD)
      for virtual reality applications. Our approach adopts an aperture mask containing
      an array of pinholes and a screen as a source of imagery. We demonstrate proof-of
      concept HMD prototypes with a binocular field of view (FOV) of 70 degrees *45
      degrees , or total diagonal FOV of 83 degrees . This FOV should increase with
      increasing display panel size. The optical angular resolution supported in our
      prototype can go down to 1.4-2.1 arcmin by adopting a display with 20-30 MUm
      pixel pitch. 

PMID- 25967332
TI  - Full determination of single ferroelectric nanocrystal orientation by Pockels
      electro-optic microscopy.
AB  - We present a nanoscale electro-optic imaging method allowing access to the phase
      response, which is not amenable to classical second-harmonic generation
      microscopy. This approach is used to infer the vectorial orientation of single
      domain ferroelectric nanocrystals, based on polarization-resolved Pockels
      microscopy. The electro-optic phase response of KTP nanoparticles yields the full
      orientation in the laboratory frame of randomly dispersed single nanoparticles,
      together with their electric polarization dipole. The complete vector
      determination of the dipole orientation is a prerequisite to important
      applications including ferroelectric nanodomain orientation, membrane potential
      imaging, and rotational dynamics of single biomolecules. 

PMID- 25967334
TI  - Improving holographic reconstruction by automatic Butterworth filtering for
      microelectromechanical systems characterization.
AB  - Digital holographic microscopy is an important interferometric tool in optical
      metrology allowing the investigation of engineered surfaces with microscale
      lateral resolution and nanoscale axial precision. In particular,
      microelectromechanical systems (MEMS) surface analysis, conducted by holographic
      characterization, requires high accuracy for functional testing. The main issues
      related to MEMS inspection are the superficial roughness and the complex geometry
      resulting from the several fabrication steps. Here, an automatic procedure,
      particularly suited in the case of high-roughness surfaces, is presented to
      selectively filter the spectrum, providing very low-noise reconstructed images.
      The numerical procedure is based on Butterworth filtering, and the obtained
      results demonstrate a significant increase in the images' quality and in the
      accuracy of the measurements, making our technique highly applicable for
      quantitative phase imaging in MEMS analysis. Furthermore, our method is fully
      tunable to the spectrum under investigation and automatic. This makes it highly
      suitable for real-time applications. Several experimental tests show the
      suitability of the proposed approach. 

PMID- 25967335
TI  - Advantages and challenges of optical coating production with indirect
      monochromatic monitoring.
AB  - In this paper, we present our recent studies on raising the quality of optical
      coating production with an indirect monochromatic monitoring system.
      Preproduction error analysis and computational manufacturing are used to estimate
      potential advantages of application of indirect optical monitoring. It is then
      demonstrated that a key issue for realization of this advantage is accurate
      specification of tooling factors for layer thicknesses on test glasses. The
      tooling factors are precalibrated using single layer depositions and then are
      corrected using results of reverse engineering for the first production run. It
      is found that a gradual variation of tooling factors of low index layers is the
      main error factor in the first deposition run. Finally, we redeposit our coating
      with a modified monitoring strategy, taking into account this factor. The new
      experimental results show excellent correspondence with the theoretical spectral
      performance. 

PMID- 25967336
TI  - Optic disc detection and boundary extraction in retinal images.
AB  - With the development of digital image processing, analysis and modeling
      techniques, automatic retinal image analysis is emerging as an important
      screening tool for early detection of ophthalmologic disorders such as diabetic
      retinopathy and glaucoma. In this paper, a robust method for optic disc detection
      and extraction of the optic disc boundary is proposed to help in the development
      of computer-assisted diagnosis and treatment of such ophthalmic disease. The
      proposed method is based on morphological operations, smoothing filters, and the
      marker controlled watershed transform. Internal and external markers are used to
      first modify the gradient magnitude image and then the watershed transformation
      is applied on this modified gradient magnitude image for boundary extraction.
      This method has shown significant improvement over existing methods in terms of
      detection and boundary extraction of the optic disc. The proposed method has
      optic disc detection success rate of 100%, 100%, 100% and 98.9% for the DRIVE,
      Shifa, CHASE_DB1, and DIARETDB1 databases, respectively. The optic disc boundary
      detection achieved an average spatial overlap of 61.88%, 70.96%, 45.61%, and
      54.69% for these databases, respectively, which are higher than currents methods.

PMID- 25967337
TI  - Simulation of octave spanning mid-infrared supercontinuum generation in
      dispersion-varying planar waveguides.
AB  - A dispersion-varying tapered planar waveguide is designed to generate
      supercontinuum efficiently in the mid-infrared region. The rib waveguide of lead
      silicate glass on silica is 1.8 cm long, consisting of a segment with
      longitudinally increasing etch depth. The mechanism involves nonlinear soliton
      dynamics. The dispersion profile is shifted along the propagation distance,
      leading to continuous modification of the phase-matching condition for dispersive
      wave (DW) emission and enhancement of energy transfer efficiency between solitons
      and DWs. With low input pulse energy of 45 pJ, simulation demonstrates the
      generation of both broadband and flat near-octave spectrum spanning 1.3-2.5 MUm
      at the -20  dB level. 

PMID- 25967338
TI  - Autonomous space target recognition and tracking approach using star sensors
      based on a Kalman filter.
AB  - When imaged by detectors, space targets (including satellites and debris) and
      background stars have similar point-spread functions, and both objects appear to
      change as detectors track targets. Therefore, traditional tracking methods cannot
      separate targets from stars and cannot directly recognize targets in 2D images.
      Consequently, we propose an autonomous space target recognition and tracking
      approach using a star sensor technique and a Kalman filter (KF). A two-step
      method for subpixel-scale detection of star objects (including stars and targets)
      is developed, and the combination of the star sensor technique and a KF is used
      to track targets. The experimental results show that the proposed method is
      adequate for autonomously recognizing and tracking space targets. 

PMID- 25967339
TI  - Phase-shift correlation method for accurate phase difference estimation in range
      finder.
AB  - High-precision phase-difference measurement is a key technology for a phase-shift
      laser range finder. In order to improve the estimation accuracy of phase
      difference between two sinusoidal signals with identical frequency, the phase
      shift correlation method is described. Theoretical analysis shows that the
      conventional cross-correlation method will bring notable deviations when the true
      phase difference is close to 0 degrees  or 180 degrees  in the presence of noise.
      For reducing the influence of noise, two step calculations--phase-shift
      autocorrelation and phase-shift cross correlation--are used in the phase-shift
      correlation method. The estimation bias is eliminated by phase-shift
      autocorrelation in which the autocorrelation is calculated between the 2pi phase
      shifted signal and the original signal, and the periodic errors are eliminated by
      phase-shift cross correlation in which the phase difference is estimated when the
      true phase difference is near 90 degrees  or 270 degrees . The effect of
      frequency drift on the phase difference is also discussed. The experiment results
      show that the maximum error of the conventional method is about 0.15 degrees ,
      while the estimation error of our proposed method is much less than 0.01 degrees 
      under the same conditions.

PMID- 25967340
TI  - Metamaterial terahertz switch based on split-ring resonator embedded with
      photoconductive silicon.
AB  - In this paper, a metamaterial terahertz (THz) switch based on a split-ring
      resonator embedded with photoconductive silicon is presented and numerically
      investigated. Simulation results show that the switch works at two different
      resonant modes with different pump light powers and that the response time of the
      switch is less than 1 ps. By defining the switching window as the frequency range
      where the transmission magnitude of the ON state is one order of magnitude higher
      than the OFF state, a switching window ranging from 1.26 to 1.49 THz is obtained.
      The large modulation depth of the switch is due to the large separations of the
      maximum and minimum transmissions, which are 0.89 and 0.01, respectively.
      Particularly, the switch is frequency tunable by changing the thickness and
      permittivity of the dielectric layer. 

PMID- 25967341
TI  - Theoretical investigation of electromagnetically induced phase grating in RF
      driven cascade-type atomic systems.
AB  - A new scheme for investigating electromagnetically induced grating in four-level
      cascade-type of 87Rb cold atoms is presented. The novel result indicates that the
      diffraction efficiency of phase grating is dramatically enhanced due to the
      presence of an RF-driven field and a diffraction efficiency up to 34% can be
      obtained. Furthermore, it is found that the frequency detuning of the applied
      laser fields with the corresponding atomic transition and the interaction length
      can improve the efficiency of the phase grating in the present atomic model. This
      work has potential applications in all-optical communication processes.

PMID- 25967342
TI  - Tomographic imaging of nonsymmetric multicomponent tailored supersonic flows from
      structured gas nozzles.
AB  - We report experimental results on the production and characterization of
      asymmetric and composite supersonic gas flows, created by merging independently
      controllable flows from multiple nozzles. We demonstrate that the spatial
      profiles are adjustable over a large range of parameters, including gas density,
      density gradient, and atomic composition. The profiles were precisely
      characterized using three-dimensional tomography. The creation and measurement of
      complex gas flows is relevant to numerous applications, ranging from laser
      produced plasmas to rocket thrusters. 

PMID- 25967344
TI  - Metal-dielectric filters for solar-blind silicon ultraviolet detectors.
AB  - We report on the fabrication of metal-dielectric thin film stacks deposited
      directly onto silicon substrates for use as ultraviolet bandpass filters.
      Integration of these filters onto silicon improves the admittance matching of the
      structure when compared to similar designs fabricated on transparent substrates,
      leading to higher peak transmission or improved out-of-band rejection if used
      with a Si-based sensor platform. Test structures fabricated with metallic Al and
      atomic layer deposited Al2O3 were characterized with spectroscopic ellipsometry
      and agree well with optical models. These models predict transmission as high as
      90% the spectral range of 200-300 nm for simple three-layer coatings.

PMID- 25967343
TI  - Field of view advantage of conjugate adaptive optics in microscopy applications.
AB  - The imaging performance of an optical microscope can be degraded by sample
      induced aberrations. A general strategy to undo the effect of these aberrations
      is to apply wavefront correction with a deformable mirror (DM). In most cases the
      DM is placed conjugate to the microscope pupil, called pupil adaptive optics
      (AO). When the aberrations are spatially variant an alternative configuration
      involves placing the DM conjugate to the main source of aberrations, called
      conjugate AO. We provide a theoretical and experimental comparison of both
      configurations for the simplified case where spatially variant aberrations are
      produced by a well-defined phase screen. We pay particular attention to the
      resulting correction field of view (FOV). Conjugate AO is found to provide a
      significant FOV advantage. While this result is well known in the astronomical
      community, our goal here is to recast it specifically for the optical microscopy
      community. 

PMID- 25967345
TI  - High brightness beam shaping and fiber coupling of laser-diode bars.
AB  - The strong beam quality mismatch in the fast and slow axes of laser-diode bars
      requires a significant beam shaping method to reach the parameters needed for
      fiber coupling. An effective solution to this problem is proposed that is based
      on a right-angle prism array and a distributed cylinder-lens stack. Coupling 12
      mini-bars into a standard 100 MUm core diameter and 0.15 numerical aperture fiber
      is achieved, and the output power can reach 400 W. Using this technique,
      production of compact and high brightness fiber-coupled laser-diode modules is
      possible. 

PMID- 25967346
TI  - Reverse design of a bull's eye structure for oblique incidence and wider angular
      transmission efficiency.
AB  - We present a design method of a bull's eye structure with asymmetric grooves for
      focusing oblique incident light. The design method is capable of designing
      transmission peaks to a desired oblique angle with capability of collecting light
      from a wider range of angles. The bull's eye groove geometry for oblique
      incidence is designed based on the electric field intensity pattern around an
      isolated subwavelength aperture on a thin gold film at oblique incidence,
      calculated by the finite difference time domain method. Wide angular transmission
      efficiency is successfully achieved by overlapping two different bull's eye
      groove patterns designed with different peak angles. Our novel design method
      would overcome the angular limitations of the conventional methods. 

PMID- 25967347
TI  - 'Bronchogenic Stress Cardiomyopathy', a Subset of Takotsubo Syndrome.

PMID- 25967348
TI  - Epigallocatechin gallate attenuated non-alcoholic steatohepatitis induced by
      methionine- and choline-deficient diet.
AB  - Nonalcoholic fatty liver disease (NAFLD) and its progressive form, nonalcoholic
      steatohepatitis (NASH), are the most common causes of chronic liver disease. In
      this study, we evaluated the effects of Epigallocatechin gallate (EGCG) on
      methionine- and choline-deficient (MCD) diet-induced NASH. Our data showed that
      EGCG significantly prevented MCD diet-induced liver and body weight loss.
      Histological analysis showed that EGCG inhibited MCD diet-induced steatohepatitis
      including fat accumulation and inflammatory cells infiltration. Biochemical
      analysis data showed that EGCG significantly reduced the elevation of plasma ALT
      and AST levels but increased plasma triglyceride and cholesterol contents.
      However, EGCG significantly inhibited hepatic triglyceride and cholesterol
      content in MCD diet fed mice. Consistent with histology results, EGCG treatment
      significantly inhibited MCD diet-induced IL-1beta, IL-6, TNF-alpha and MCP-1 mRNA
      expression. As an antioxidant, EGCG treatment significant inhibited hepatic MDA
      contents and increased hepatic SOD contents. In addition, transforming growth
      factor (TGF)-beta, collagen I-alpha1, tissue inhibitor of metalloproteinase 1
      (TIMP-1) and alpha-smooth muscle actin (SMA) mRNA expression, which are markers
      of hepatic fibrosis, were markedly inhibited by EGCG treatment. Western blot data
      showed that EGCG inhibited Smad2 and Smad3 phosphorylation in the liver and LX-2
      cells which were involved in TGF-beta-induced pathway. Taken together, EGCG
      attenuated NASH induced by MCD diet associated with ameliorating fibrosis,
      oxidative stress, and hepatic inflammation. Our results indicate that EGCG has
      beneficial roles in the development of MCD diet-induced NASH. 

PMID- 25967349
TI  - Role of phospholipases D1 and 2 in astroglial proliferation: effects of specific
      inhibitors and genetic deletion.
AB  - Phospholipase D (PLD) activity has been linked to proliferation in many cell
      types including tumor cells. In the present study, we investigated the effects of
      genetic deletion of PLD1 and PLD2 and of specific PLD1 and PLD2 inhibitors on PLD
      activity and cell proliferation in primary mouse astrocytes. Basal and stimulated
      PLD activity was negligible in PLD1/2 double knockouts. PLD activity was
      significantly reduced in PLD1-deficient cells when fetal calf serum (FCS),
      insulin-like growth factor 1 (IGF-1) or phorbol ester was used as a stimulant.
      The specificity of PLD inhibitors VU0359595 and VU0285655-1 at 500nM was
      confirmed in phorbol ester-stimulated cells. Significant reductions of cell
      proliferation were observed in PLD-deficient cell lines under basal and
      stimulated conditions. At 500nM, the PLD1 inhibitor VU0359595 reduced
      proliferation in PLD2-deficient cells, but also in PLD1-deficient cells
      stimulated by IGF-1 or phorbol ester. Vice versa, at 500nM, the PLD2 inhibitor
      VU0285655-1 reduced proliferation in PLD1-deficient cells, but also in PLD2
      deficient cells exposed to IGF-1. At 5uM, both inhibitors showed non-specific
      effects because they inhibited cell proliferation even in PLD1/2 double
      knockouts. Summarizing, inhibition of PLD occurs in parallel with reduced cell
      proliferation in astrocytes which are deficient in PLD1 or PLD2. Synthetic PLD
      inhibitors show high specificity for PLD in low (nanomolar) concentrations, but
      have additional, non-specific effects on cell proliferation when used at high
      (micromolar) concentrations. 

PMID- 25967351
TI  - The Effects of Melatonin on Brain Arginine Vasotocin: Relationship with Sex and
      Seasonal Differences in Melatonin Receptor Type 1 in Green Treefrogs (Hyla
      cinerea).
AB  - The neuroendocrine mechanisms by which animals synchronise their physiological
      state with environmental cues are vital to timing life-history events
      appropriately. One important endocrine transducer of environmental cues in
      vertebrates is the pineal hormone melatonin, the secretion of which is directly
      sensitive to photoperiod and temperature. Melatonin modulates arginine vasotocin
      (AVT)-immunoreactive (-IR) cell number in the brain of green treefrogs (Hyla
      cinerea) during the summer breeding season, and this modulation is sexually
      dimorphic. In the present study, we investigated whether the influence of
      melatonin on vasotocin varies seasonally. We show that treatment of
      nonreproductive male green treefrogs with melatonin-filled silastic implants for
      4 weeks during the winter does not alter vasotocin-IR cell number in any brain
      region (i.e. nucleus accumbens, amygdala, preoptic area, suprachiasmatic nucleus
      or ventral hypothalamus). Taken together, these results suggest that the
      influence of melatonin on AVT is associated with sex and seasonal variation in
      melatonin receptor expression. We tested this hypothesis by using
      immunohistochemistry to characterise the distribution of melatonin receptor type
      1 (MT1, also known as Mel1a) in the brain of reproductive and nonreproductive
      male and female frogs. We quantified MT1-IR cell number in regions known to
      contain AVT cell populations. Reproductive males had significantly more MT1-IR
      cells than nonreproductive males in all brain regions, including the combined
      nucleus accumbens, diagonal band of Broca and septum, striatum, amygdala,
      combined preoptic area and suprachiasmatic nucleus, as well as the ventral
      hypothalamus. In the accumbens region, where the effect of melatonin on AVT is
      known to be sexually dimorphic, males had significantly more MT1-IR cells than
      females during the summer breeding season. Based on these findings, we suggest
      that MT1 plays a role in mediating the interactions between melatonin and
      vasotocin that regulate seasonal and sexually dimorphic changes in sociosexual
      behaviour. 

PMID- 25967350
TI  - POxylated Polyurea Dendrimers: Smart Core-Shell Vectors with IC50 Lowering
      Capacity.
AB  - The design and preparation of highly efficient drug delivery platforms using
      green methodologies is at the forefront of nanotherapeutics research. POxylated
      polyurea dendrimers are efficiently synthesized using a supercritical-assisted
      polymerization in carbon dioxide. These fluorescent, pH-responsive and water
      soluble core-shell smart nanocarriers show low toxicity in terms of cell
      viability and absence of glutathione depletion, two of the major side effect
      limitations of current vectors. The materials are also found to act as good
      transfection agents, through a mechanism involving an endosomal pathway, being
      able to reduce 100-fold the IC50 of paclitaxel. 

PMID- 25967352
TI  - Therapy for hepatitis C genotype 3: moving forward.
AB  - Until recently, the standard of care for hepatitis C virus genotype 3 infection
      was response-guided therapy with pegylated interferon plus ribavirin for 16 to 48
      or 72 weeks. The introduction of sofosbuvir plus ribavirin has revolutionized
      hepatitis C virus therapy. Nowadays, the recommend treatment regimen is a
      combination of sofosbuvir and a weight-based ribavirin dose for 24 weeks. For
      easy to treat patients (e.g. naive or previously treated patients without
      cirrhosis), this combination achieves high sustained virologic response rates and
      is well tolerated. However, in treatment-experienced patients with cirrhosis,
      sustained virologic response is lower due to unknown reasons. The combination of
      two direct-acting antiviral agents, sofosbuvir and daclatasvir, for 12 weeks is
      also associated with low sustained virologic response rates in this special
      population, for whom new drugs and different strategies are now under evaluation.
      Currently, the high cost of all these drugs limits access to treatment in many
      countries.

PMID- 25967354
TI  - Radiological Features in Patients with Short Stature Homeobox-Containing (SHOX)
      Gene Deficiency and Turner Syndrome before and after 2 Years of GH Treatment.
AB  - BACKGROUND/AIMS: The short stature homeobox-containing (SHOX) gene is one of many
      genes that regulate longitudinal growth. The SHOX deficiency (SHOX-D) phenotype,
      caused by intragenic or regulatory region defects, ranges from normal stature to
      mesomelic skeletal dysplasia. We investigated differences in radiological
      anomalies between patients with SHOX-D and Turner syndrome (TS) and the effect of
      2 years of growth hormone (GH) treatment on these anomalies. METHODS: Left
      hand/wrist, forearm and lower leg radiographs were assessed at baseline and after
      2 years in children with genetically confirmed SHOX-D (GH-treated and untreated
      groups) and TS (GH-treated) in a randomised, controlled, multinational study.
      RESULTS: Radiological anomalies of hand, wrist and forearm were common in SHOX-D
      and TS. Radial bowing appeared more prevalent in SHOX-D, while lower leg
      anomalies were more common in TS. There were no significant differences in
      radiological findings between GH-treated and untreated patients with SHOX-D after
      2 years. CONCLUSION: GH treatment had no systematic effect on skeletal findings
      in SHOX-D, based on limited radiological differences between the GH-treated and
      untreated groups at 2 years. Bone age radiographs allow assessment of
      radiological signs indicating a potential diagnosis of SHOX-D and may lead to
      earlier genetic confirmation and initiation of GH therapy.

PMID- 25967353
TI  - Multiplatform metabolomic fingerprinting as a tool for understanding
      hypercholesterolemia in Wistar rats.
AB  - PURPOSE: The aim was to investigate the impact of hypercholesterolemic diet on
      the metabolome of male Wistar rats by a multiplatform metabolomic fingerprinting.
      METHODS: Male Wistar rats were fed with two different diets [control (C) and high
      cholesterol diet (HC)-containing 2 % cholesterol and 0.5 % cholic acid]. After 7
      weeks of experimental feeding, the rats were euthanized for blood collection and
      plasma recovery. The metabolite fingerprint was then achieved by applying a
      multiplatform comprising LC-MS, GC-MS and CE-MS. RESULTS: Multivariate
      statistical analysis showed a clear separation between the C and HC groups.
      Individual differences in metabolites were evaluated using univariate statistical
      analysis, and multiple metabolites were identified and confirmed in the plasma. A
      global profiling integrates for the first time pathways affected by high
      cholesterol diet intake and allowed us to elucidate some of the associated
      alterations underlying the hypercholesterolemia event in Wistar rats.
      CONCLUSIONS: HC feeding stimulated the alteration of multiple pathways in Wistar
      rats, warning of the risk of developing important diseases, which can be
      modulated by the diet. Further studies are required to investigate the
      possibilities to revert or ameliorate the negative effects triggered by HC
      intake.

PMID- 25967356
TI  - Association between chronic stress and blood pressure: findings from the German
      Health Interview and Examination Survey for Adults 2008-2011.
AB  - OBJECTIVE: The magnitude of the contribution of psychosocial stressors to the
      development of hypertension remains controversial. Using data from the population
      based, nationwide German Health Interview and Examination Survey for Adults, we
      investigated the relationship between objectively measured and subjectively
      perceived stressors and blood pressure (BP). METHODS: The study sample comprised
      3352 participants not taking antihypertensive medication, for whom data on stress
      exposure and resting BP measurements were available. The Trier Inventory for the
      Assessment of Chronic Stress screening scale (TICS-SSCS) was used as a
      measurement of self-perceived chronic stress, and work-related stress was
      assessed using the recently developed occupational Overall Job Index. RESULTS: On
      the basis of bivariate tests, TICS-SSCS was negatively associated with both
      systolic (beta-coefficient [B] = -0.16, standard error = 0.03, p < .001) and
      diastolic BP (B = -0.10, standard error = 0.02, p < .001). After adjustment for
      age, sex, and body mass index, the TICS-SSCS but not the Overall Job Index was
      significantly related to systolic and diastolic BP. When alcohol consumption,
      smoking, physical activity, residential traffic intensity, caregiving,
      socioeconomic status, social support, and living without a partner were added to
      the model, the TICS-SSCS again remained independently associated with both BP
      measures (p <= .007). CONCLUSIONS: In a large and representative German study, we
      found that less perceived stress is associated with higher BP levels, whereas the
      exposure to objective stressors was unrelated to BP. These findings suggest that
      stress perception and objective stressors influence BP regulation via different
      biobehavioral pathways.

PMID- 25967355
TI  - Association between major depression and type 2 diabetes in midlife: findings
      from the Screening Across the Lifespan Twin Study.
AB  - OBJECTIVE: Cohort studies suggest that the relationship between major depression
      (MD) and Type 2 diabetes (T2DM) is bidirectional. However, this association may
      be confounded by shared genetic or environmental factors. The objective of this
      study was to use a twin design to investigate the association between MD and
      T2DM. METHODS: Data come from the Screening Across the Lifespan Twin Study, a
      sample of monozygotic and dizygotic twins 40 years or older sampled from the
      Swedish Twin Registry (n = 37,043). MD was assessed by using the Composite
      International Diagnostic Inventory. Structural equation twin modeling and Cox
      proportional hazards modeling were used to assess the relationship between MD and
      T2DM. RESULTS: Approximately 19% of respondents had a history of MD and 5% had a
      history of T2DM. MD was associated with 32% increased likelihood of T2DM (95%
      confidence interval = 1.00-1.80) among twins aged 40 to 55 years, even after
      accounting for genetic risk, but was not associated with T2DM among twins older
      than 55 years. T2DM was associated with 33% increased likelihood of MD (95%
      confidence interval = 1.02-1.72) among younger, but not older twins. Cholesky
      decomposition twin modeling indicated that common unique environmental factors
      contribute to the association between MD and T2DM. CONCLUSIONS: Environmental
      factors that are unique to individuals (i.e., not shared within families) but
      common to both MD and T2DM contribute to their co-occurrence in midlife. However,
      we cannot exclude the possibility of bidirectional causation as an alternate
      explanation. It is likely that multiple processes are operating to effect the
      relation between psychiatric and medical conditions in midlife.

PMID- 25967358
TI  - RAGE and its ligands in cancer - culprits, biomarkers, or therapeutic targets?
AB  - Receptor for advanced glycation end products (RAGE) plays a central role in the
      regulation of tissue homeostasis, regeneration and resolution of inflammation,
      but under pathological conditions RAGE-mediated pathways may induce diminished
      apoptosis, but enhanced autophagy and cell necrosis. These mechanisms may
      contribute to malignant transformation, cancer progression and metastases.
      Soluble RAGE may bind natural RAGE ligands and counteract some of the RAGE
      mediated effects. Activation of RAGE was demonstrated in different types of
      cancer (including colon, pancreatic and breast cancer). Expression of RAGE and
      serum levels of soluble RAGE may serve as cancer biomarkers and strategies aimed
      at interfering with RAGE signaling might be promising anticancer drugs. 

PMID- 25967357
TI  - Temperament characteristics in patients with panic disorder and their first
      degree relatives.
AB  - AIM: Panic disorder is one of the highly heritable anxiety disorders; and
      temperament characteristics are considered predicting liability to panic
      disorder. Accumulating evidence suggests temperament characteristics are
      intermediate phenotypes for clinical conditions. Given this background, we aimed
      to investigate temperament characteristics in patients with panic disorder, their
      first-degree relatives, and healthy controls. METHOD: Study sample consisted of
      60 patients with panic disorder, 37 first-degree relatives of these patients, and
      37 age, gender, and education level matched healthy controls (HC). SCID-I, the
      Panic Agoraphobia Scale, and the State and Trait Anxiety Inventory were applied
      to assess clinical characteristics of the patient group. Temperament
      characteristics were assessed using the Temperament Evaluation of Memphis, Pisa,
      Paris, San Diego Autoquestionnaire (TEMPS-A). RESULTS: Anxious, depressive,
      cyclothymic, and irritable temperament scores of patients were higher than those
      of HC. There was no difference between the patients and the relatives, with the
      exception of higher anxious temperament scores in patients. CONCLUSION: Overall,
      our findings suggest that anxious temperament characteristic might be a trait
      marker for liability to panic disorder. Further research with a prospective
      design in a larger sample is required to confirm our findings.

PMID- 25967359
TI  - Prognostic implication of the loss of TGFBR2 expression in oral carcinoma.
AB  - Oral squamous cell carcinoma (OSCC) is a disease that strikes many worldwide,
      accounting for more than 145,000 deaths annually. This study examined the role of
      Transforming Growth Factor Beta (TGFbeta) signalling alterations in oral
      carcinogenesis and also its influence on the disease prognosis. In presented
      study, we evaluated the protein-level alterations of core TGFbeta signalling
      members in 20 potentially malignant oral disorders (PMDs) - leukoplakia and
      submucous fibrosis and 87 oral cancer samples by western blotting. Further, we
      analysed the association between these alterations and prognosis of oral
      carcinoma. For statistical analyses, univariate test like Student's 't'-test to
      compare expression level of various genes and logrank test has been used to
      compare the Kaplan-Meier survival curves. The multivariate model such as Cox's
      proportional hazard regression was used to verify the independent influence of
      each variable on the survival endpoints. A gradual decrease in the expression of
      TGFbeta signalling members like SMAD2, SMAD4, TGFBR1 and TGFBR2 have been noted
      from normal to PMD in oral cancers. The bio-activeforms, SMAD2/3 also showed a
      similar trend. SMAD3 protein was downregulated significantly in the PMD stage
      itself. Thus an inverse correlation was observed between expression of TGFbeta
      members and oral cancer progression.Furthermore, oral cancer patients showing
      TGFBR2 downregulation exhibited poor disease-free survival (p=0.005) and poor
      overall survival (p=0.012).Thus, assessing the TGFBR2 protein levels can serve as
      one of the prognostic marker for oral cancer. 

PMID- 25967360
TI  - Involvement of SRPK1 in cisplatin resistance related to long non-coding RNA UCA1
      in human ovarian cancer cells.
AB  - The therapeutic potential of cisplatin in ovarian cancer treatment is restricted
      by the occurrence of cellular resistance. We aimed to explore the role of SRPK1
      in cisplatin resistance related to the long non-coding RNA UCA1 in ovarian cancer
      cell.Totally, 24 ovarian cancer tissues and 16 normal tissues were used to assess
      the expression of UCA1 RNA. UCA1 stable transfected SKOV3 cells were established
      and the ability of cell migration, invasion and cisplatin resistance was
      assessed. The expression of SRPK1 and apoptosis pathway proteins was then
      assessed to explore the mechanism. In addition, SRPK1 knockdown cell line was
      also established and the effects of SRPK1 on cell migration, invasion and
      cisplatin resistance was evaluated.Elevated expression of UCA1 RNA was identified
      in ovarian cancer tissues compared with normal tissues. Expression of UCA1 RNA in
      SKOV3 cells enhanced the cell migration, invasion and cisplatin resistance.
      Increased expression of SRPK1 and anti-apoptosis proteins were found in
      SKOV3/pcDNA-UCA1 cells. Knocking-down SRPK1 could partly rescue the effect of
      UCA1 expression on cell migration, invasion and cisplatin resistance in SKOV3
      cells.Elevated expression of UCA1 RNA was found in ovarian cancer tissues. UCA1
      can improve the cell migration, invasion and induce cisplatin resistance. SRPK1
      and apoptosis pathway proteins may be involved in the effect of UCA1. 

PMID- 25967361
TI  - Foreword: Calcified Tissue International and Musculoskeletal Research Special
      Issue: Bone Material Properties and Skeletal Fragility.

PMID- 25967363
TI  - Ketene as a Reaction Intermediate in the Carbonylation of Dimethyl Ether to
      Methyl Acetate over Mordenite.
AB  - Unprecedented insight into the carbonylation of dimethyl ether over Mordenite is
      provided through the identification of ketene (CH2CO) as a reaction intermediate.
      The formation of ketene is predicted by detailed DFT calculations and verified
      experimentally by the observation of doubly deuterated acetic acid (CH2DCOOD),
      when D2O is introduced in the feed during the carbonylation reaction.

PMID- 25967362
TI  - Mechanical loading reduces inflammation-induced human osteocyte-to-osteoclast
      communication.
AB  - Multiple factors contribute to bone loss in inflammatory diseases such as
      rheumatoid arthritis (RA), but circulating inflammatory factors and
      immobilization play a crucial role. Mechanical loading prevents bone loss in the
      general population, but the effects of mechanical loading in patients with RA are
      less clear. Therefore, we aimed to investigate whether mechanical stimuli reverse
      the stimulatory effect of RA serum on osteocyte-to-osteoclast communication.
      Human primary osteocytes were pretreated with 10 % RA serum or healthy control
      serum for 7 days, followed by 1 h +/- mechanical loading by pulsating fluid flow
      (PFF). Nitric oxide (NO) and prostaglandin E2 were measured in the medium.
      Receptor activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin
      (OPG), interleukin-6 (IL-6), cyclooxygenase-2 (COX2), matrix-extracellular
      phosphoglycoprotein (MEPE), cysteine-rich protein 61 (CYR61), and SOST gene
      expression was quantified by qPCR. Osteoclast precursors were cultured with PFF
      conditioned medium (PFF-CM) or static-conditioned medium (stat-CM), and
      osteoclast formation was assessed. RA serum alone did not affect IL-6, CYR61,
      COX2, MEPE, or SOST gene expression in osteocytes. However, RA serum enhanced the
      RANKL/OPG expression ratio by 3.4-fold, while PFF nullified this effect. PFF
      enhanced NO production to the same extent in control serum (2.6-3.5-fold) and RA
      serum-pretreated (2.7-3.6-fold) osteocytes. Stat-CM from RA serum-pretreated
      osteocytes enhanced osteoclastogenesis compared with stat-CM from control serum
      pretreated osteocytes, while PFF nullified this effect. In conclusion, RA serum,
      containing inflammatory factors, did not alter the intrinsic capacity of
      osteocytes to sense mechanical stimuli, but upregulated osteocyte-to-osteoclast
      communication. Mechanical loading nullified this upregulation, suggesting that
      mechanical stimuli could contribute to the prevention of osteoporosis in
      inflammatory disease.

PMID- 25967364
TI  - The functional foetal brain: A systematic preview of methodological factors in
      reporting foetal visual and auditory capacity.
AB  - Due to technological advancements in functional brain imaging, foetal brain
      responses to visual and auditory stimuli is a growing area of research despite
      being relatively small with much variation between research laboratories. A
      number of inconsistencies between studies are, nonetheless, present in the
      literature. This article aims to explore the potential contribution of
      methodological factors to variation in reports of foetal neural responses to
      external stimuli. Some of the variation in reports can be explained by
      methodological differences in aspects of study design, such as brightness and
      wavelength of light source. In contrast to visual foetal processing, auditory
      foetal processing has been more frequently investigated and findings are more
      consistent between different studies. This is an early preview of an emerging
      field with many articles reporting small sample sizes with techniques that are
      yet to be replicated. We suggest areas for improvement for the field as a whole,
      such as the standardisation of stimulus delivery and a more detailed reporting of
      methods and results. This will improve our understanding of foetal functional
      response to light and sound. We suggest that enhanced technology will allow for a
      more reliable description of the developmental trajectory of foetal processing of
      light stimuli. 

PMID- 25967365
TI  - Effect of Dimethoate on the Activity of Hepatic CYP450 Based on Pharmacokinetics
      of Probe Drugs.
AB  - BACKGROUND: Dimethoate (DM), one of the most widely used systemic organophosphate
      insecticide, has been reported to exert toxic effects after long-time subchronic
      exposure. This study aims at investigating the toxic effect of DM on liver after
      repeated administration of low doses of DM in rats. METHODS: Twenty Sprague
      Dawley rats were randomly divided into the control group (n = 10) and the DM
      group (n = 10). After 2 weeks' exposure to DM at low dosage (5 mg/kg),
      biochemical parameters of hepatic functions were measured, histology and CYP450
      expressed in liver was detected. The activities of CYP1A2, CYP2C11, CYP2D1, and
      CYP3A2 were evaluated by the Cocktail method. RESULTS: The level of AChE
      (acetylcholinesterase) was significantly decreased, hepatic functions were
      damaged and the mRNA level of CYP2D1 was significantly increased in the DM group
      (p < 0.05). The pharmacokinetics of probe drug revealed AUC(0-t), AUC(0
      infinity), t1/2 and Cmax of metoprolol was shorten in the DM group (p < 0.05).
      However, there were no statistical differences in MRT, t1/2, CL and Tmax for
      phenacetin, tolbutamide and midazolam. CONCLUSIONS: A low dosage of DM could
      induce the activity of CYP2D1 in liver and increase the metabolism of metoprolol
      when exposed for 2 weeks.

PMID- 25967366
TI  - Microvascular Lesions at the Bottom of the Brain: New Neuropathological Insights.

PMID- 25967367
TI  - Corneal depression immediately after cardiac surgery.

PMID- 25967369
TI  - The EnvIMS Study: Design and Methodology of an International Case-Control Study
      of Environmental Risk Factors in Multiple Sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) is a chronic disease of the central nervous
      system, often resulting in significant neurological disability. The causes of MS
      are not known; however, the incidence of MS is increasing, thereby suggesting
      that changes in lifestyle and/or environmental factors may be responsible. On
      this background, the Environmental Risk Factors in MS Study or EnvIMS study was
      designed to further explore the etiology of MS. The design and methodology are
      described, providing details to enable investigators to (i) use our experiences
      to design their own studies; (ii) take advantage of, and build on the
      methodological work completed for, the EnvIMS study; (iii) become aware of this
      data source that is available for use by the research community. METHODS: EnvIMS
      is a multinational case-control study, enrolling 2,800 cases with MS and 5,012
      population-based controls in Canada, Italy, Norway, Serbia and Sweden. The study
      was designed to investigate the most commonly implicated risk factors for MS
      etiology using a self-report questionnaire. RESULTS/CONCLUSIONS: The use of a
      common methodology to study MS etiology across several countries enhances the
      comparability of results in different geographic regions and research settings,
      reduces the resources required for study design and enhances the opportunity for
      data harmonization.

PMID- 25967370
TI  - The portuguese pulmonology journal on the science citation index.

PMID- 25967368
TI  - Sedentary behaviour and physical activity in bronchiectasis: a cross-sectional
      study.
AB  - BACKGROUND: The impact of bronchiectasis on sedentary behaviour and physical
      activity is unknown. It is important to explore this to identify the need for
      physical activity interventions and how to tailor interventions to this patient
      population. We aimed to explore the patterns and correlates of sedentary
      behaviour and physical activity in bronchiectasis. METHODS: Physical activity was
      assessed in 63 patients with bronchiectasis using an ActiGraph GT3X+
      accelerometer over seven days. Patients completed: questionnaires on health
      related quality-of-life and attitudes to physical activity (questions based on an
      adaption of the transtheoretical model (TTM) of behaviour change); spirometry;
      and the modified shuttle test (MST). Multiple linear regression analysis using
      forward selection based on likelihood ratio statistics explored the correlates of
      sedentary behaviour and physical activity dimensions. Between-group analysis
      using independent sample t-tests were used to explore differences for selected
      variables. RESULTS: Fifty-five patients had complete datasets. Average daily
      time, mean(standard deviation) spent in sedentary behaviour was 634(77)mins,
      light-lifestyle physical activity was 207(63)mins and moderate-vigorous physical
      activity (MVPA) was 25(20)mins. Only 11% of patients met recommended guidelines.
      Forced expiratory volume in one-second percentage predicted (FEV1% predicted) and
      disease severity were not correlates of sedentary behaviour or physical activity.
      For sedentary behaviour, decisional balance 'pros' score was the only correlate.
      Performance on the MST was the strongest correlate of physical activity. In
      addition to the MST, there were other important correlate variables for MVPA
      accumulated in >=10-minute bouts (QOL-B Social Functioning) and for activity
      energy expenditure (Body Mass Index and QOL-B Respiratory Symptoms). CONCLUSIONS:
      Patients with bronchiectasis demonstrated a largely inactive lifestyle and few
      met the recommended physical activity guidelines. Exercise capacity was the
      strongest correlate of physical activity, and dimensions of the QOL-B were also
      important. FEV1% predicted and disease severity were not correlates of sedentary
      behaviour or physical activity. The inclusion of a range of physical activity
      dimensions could facilitate in-depth exploration of patterns of physical
      activity. This study demonstrates the need for interventions targeted at reducing
      sedentary behaviour and increasing physical activity, and provides information to
      tailor interventions to the bronchiectasis population. TRIAL REGISTRATION:
      NCT01569009 ("Physical Activity in Bronchiectasis").

PMID- 25967371
TI  - Age- and sex-specific dynamics in 22 hematologic and biochemical analytes from
      birth to adolescence.
AB  - BACKGROUND: Pediatric laboratory test results must be interpreted in the context
      of interindividual variation and age- and sex-dependent dynamics. Reference
      intervals as presently defined for separate age groups can only approximate the
      age-related dynamics encountered in pediatrics. Continuous reference intervals
      from birth to adulthood are not available for most laboratory analytes because of
      the ethical and practical constraints of defining reference intervals using a
      population of healthy community children. We applied an indirect method to
      generate continuous reference intervals for 22 hematologic and biochemical
      analytes by analyzing clinical laboratory data from blood samples taken during
      clinical care of patients. METHODS: We included samples from 32 000 different
      inpatients and outpatients (167 000 samples per analyte) from a German pediatric
      tertiary care center. Measurements were performed on a Sysmex-XE 2100 and a Cobas
      Integra 800 during clinical care over a 6-year period. The distribution of
      samples considered normal was estimated with an established indirect statistical
      approach and used for the calculation of reference intervals. RESULTS: We provide
      continuous reference intervals from birth to adulthood for 9 hematology analytes
      (hemoglobin, hematocrit, red cell indices, red cell count, red cell distribution
      width, white cell count, and platelet count) and 13 biochemical analytes (sodium,
      chloride, potassium, calcium, magnesium, phosphate, creatinine, aspartate
      transaminase, alanine transaminase, gamma-glutamyltransferase, alkaline
      phosphatase, lactate dehydrogenase, and total protein). CONCLUSIONS: Continuous
      reference intervals capture the population changes in laboratory analytes during
      pediatric development more accurately than age groups. After local validation,
      the reference intervals provided should allow a more precise consideration of
      these dynamics in clinical decision making.

PMID- 25967374
TI  - Kinematic HAADF-STEM image simulation of small nanoparticles.
AB  - The high-angle annular dark field-scanning transmission electron microscopy
      (HAADF-STEM) has been widely used in nanoparticle characterization due to its
      relatively straightforward interpretability, although multislice simulation is
      often required in order to take into account the strong dynamical screening
      effect if quantitative structure information is needed. The multislice simulation
      is very time-consuming, which can be a hurdle in cases when one has to deal with
      a large set of images. In this paper, we introduce a simple computer program,
      based on kinematic-scattering method, which allows users to simulate HAADF-STEM
      images of small nanoparticles, in 'real time' on a standard desktop computer. By
      comparing with the sophisticated multislice simulation, we demonstrate that such
      an approach is adequate for nanoparticles of ~3 nm in diameter (assuming an
      approximately spherical shape), particularly away from strict zone axis
      conditions. As an application, we show that the efficient kinematic simulation
      allows quick identification of orientation of nanoparticles.

PMID- 25967373
TI  - Calcilytic Ameliorates Abnormalities of Mutant Calcium-Sensing Receptor (CaSR)
      Knock-In Mice Mimicking Autosomal Dominant Hypocalcemia (ADH).
AB  - Activating mutations of calcium-sensing receptor (CaSR) cause autosomal dominant
      hypocalcemia (ADH). ADH patients develop hypocalcemia, hyperphosphatemia, and
      hypercalciuria, similar to the clinical features of hypoparathyroidism. The
      current treatment of ADH is similar to the other forms of hypoparathyroidism,
      using active vitamin D3 or parathyroid hormone (PTH). However, these treatments
      aggravate hypercalciuria and renal calcification. Thus, new therapeutic
      strategies for ADH are needed. Calcilytics are allosteric antagonists of CaSR,
      and may be effective for the treatment of ADH caused by activating mutations of
      CaSR. In order to examine the effect of calcilytic JTT-305/MK-5442 on CaSR
      harboring activating mutations in the extracellular and transmembrane domains in
      vitro, we first transfected a mutated CaSR gene into HEK cells. JTT-305/MK-5442
      suppressed the hypersensitivity to extracellular Ca(2+) of HEK cells transfected
      with the CaSR gene with activating mutations in the extracellular and
      transmembrane domains. We then selected two activating mutations locating in the
      extracellular (C129S) and transmembrane (A843E) domains, and generated two
      strains of CaSR knock-in mice to build an ADH mouse model. Both mutant mice
      mimicked almost all the clinical features of human ADH. JTT-305/MK-5442 treatment
      in vivo increased urinary cAMP excretion, improved serum and urinary calcium and
      phosphate levels by stimulating endogenous PTH secretion, and prevented renal
      calcification. In contrast, PTH(1-34) treatment normalized serum calcium and
      phosphate but could not reduce hypercalciuria or renal calcification. CaSR knock
      in mice exhibited low bone turnover due to the deficiency of PTH, and JTT-305/MK
      5442 as well as PTH(1-34) increased bone turnover and bone mineral density (BMD)
      in these mice. These results demonstrate that calcilytics can reverse almost all
      the phenotypes of ADH including hypercalciuria and renal calcification, and
      suggest that calcilytics can become a novel therapeutic agent for ADH.

PMID- 25967372
TI  - Nuclear cyclophilins affect spliceosome assembly and function in vitro.
AB  - Cyclophilins are ubiquitously expressed proteins that bind to prolines and can
      catalyse cis/trans isomerization of proline residues. There are 17 annotated
      members of the cyclophilin family in humans, ubiquitously expressed and localized
      variously to the cytoplasm, nucleus or mitochondria. Surprisingly, all eight of
      the nuclear localized cyclophilins are found associated with spliceosomal
      complexes. However, their particular functions within this context are unknown.
      We have therefore adapted three established assays for in vitro pre-mRNA splicing
      to probe the functional roles of nuclear cyclophilins in the context of the human
      spliceosome. We find that four of the eight spliceosom-associated cyclophilins
      exert strong effects on splicing in vitro. These effects are dose-dependent and,
      remarkably, uniquely characteristic of each cyclophilin. Using both qualitative
      and quantitative means, we show that at least half of the nuclear cyclophilins
      can act as regulatory factors of spliceosome function in vitro. The present work
      provides the first quantifiable evidence that nuclear cyclophilins are splicing
      factors and provides a novel approach for future work into small molecule-based
      modulation of pre-mRNA splicing. 

PMID- 25967375
TI  - Preparation of micro-foils for TEM/STEM analysis from metallic powders.
AB  - A technique has been developed which facilitates the preparation of electro
      polished micro-foil transmission electron microscopy (TEM) specimens, which have
      previously been machined out of ~100 MUm diameter metallic powder particles using
      a Focussed Ion Beam (FIB) instrument. The technique can be used to create small
      volume TEM specimens from most metallic powder particles and bulk metal samples.
      This is especially useful when the matrices are ferritic steels, which are often
      difficult to image in the electron microscope, since the necessary aberration
      corrections change as the sample is tilted in the magnetic field of the objective
      lens. Small samples, such as powder particles, were attached to gold support
      grids using deposited platinum and were then ion milled to approximately 2 MUm
      thickness in a focussed ion beam (FIB) instrument. Subsequently, the specimen
      assemblies were electropolished for short durations under standard conditions, to
      produce large (5 MUm*5 MUm) electron transparent regions of material. The
      specimens produced by this technique were free from FIB related artefacts and
      facilitated atomic resolution scanning-TEM (STEM) imaging of ferritic and nickel
      matrices containing, for example, yttrium rich oxide nano-dispersoids.

PMID- 25967376
TI  - Effect of trimetallization in thiolate-protected Au(24-n)Cu(n)Pd clusters.
AB  - We synthesized a mixture of Au24-nCunPd(SC12H25)18 (n = 0-3) and Au25
      nCun(SC12H25)18 (n = 0-7) and compared their stability. The results showed that,
      in a cluster containing one Cu atom, the presence of Pd is effective in improving
      the cluster stability. Conversely, the presence of Pd has different effects
      depending on the number of Cu atoms in the cluster: cluster formation was
      inhibited for clusters containing four or more Cu atoms. 

PMID- 25967377
TI  - Iron overload in transfusion-dependent thalassemia.

PMID- 25967378
TI  - Effectiveness of body-mind-spirit intervention on well-being, functional
      impairment and quality of life among depressive patients - a randomized
      controlled trial.
AB  - AIM: The aim of the study was to examine the efficacy of body-mind-spirit
      Intervention in improving the outcomes (well-being, quality of life and
      functional impairment) among depressive patients. BACKGROUND: Depressive
      disorders lead to significant dysfunction, disability and poor quality of life
      among sufferers. Body-mind-spirit intervention has been associated with
      improvements in the outcomes; however, few studies have examined this among
      depressive patients. DESIGN: True experimental pre-post equivalent groups design
      was adopted with longitudinal measurement of outcomes. METHODS: Participants were
      120 adult depressive patients visiting the psychiatric outpatient department in a
      District Hospital in India. The participants were randomly assigned to either the
      body-mind-spirit group or the treatment-as-usual group between July 2011-January
      2013. The treatment-as-usual group (n = 64) received only routine treatment
      (antidepressants and structured psycho-education) in the hospital. The body-mind
      spirit group (n = 56) received four weekly body-mind-spirit group sessions in
      addition to the routine treatment. Outcome measures on depression, well-being,
      functional impairment and quality of life were evaluated for both groups at
      baseline and at four follow-up assessments in the 1st, 2nd, 3rd and 6th month.
      Treatment effects of the body-mind-spirit intervention were analysed by repeated
      measures analysis of covariance. FINDINGS: Compared with the treatment-as-usual
      group, the body-mind-spirit group showed significant reduction in depression and
      functional impairment, and significant improvement in the well-being and quality
      of life scores over the 6-month study period. CONCLUSION: The present findings
      provided evidence for the effectiveness of integrating a complementary therapy
      such as the body-mind-spirit intervention with conventional treatment in
      improving prospective outcomes among the depressive patients.

PMID- 25967379
TI  - Backbone and side chain NMR assignments of Geobacillus stearothermophilus ZapA
      allow identification of residues that mediate the interaction of ZapA with FtsZ.
AB  - Bacterial division begins with the formation of a contractile protein ring at
      midcell, which constricts the bacterial envelope to generate two daughter cells.
      The central component of the division ring is FtsZ, a tubulin-like protein
      capable of self-assembling into filaments which further associate into a higher
      order structure known as the Z ring. Proteins that bind to FtsZ play a crucial
      role in the formation and regulation of the Z ring. One such protein is ZapA, a
      widely conserved 21 kDa homodimeric protein that associates with FtsZ filaments
      and promotes their bundling. Although ZapA was discovered more than a decade ago,
      the structural details of its interaction with FtsZ remain unknown. In this work,
      backbone and side chain NMR assignments for the Geobacillus stearothermophilus
      ZapA homodimer are described. We titrated FtsZ into (15)N(2)H-ZapA and mapped
      ZapA residues whose resonances are perturbed upon FtsZ binding. This information
      provides a structural understanding of the interaction between FtsZ and ZapA. 

PMID- 25967380
TI  - Determination of fetal DNA fraction from the plasma of pregnant women using
      sequence read counts.
AB  - OBJECTIVE: This study introduces a novel method, referred to as SeqFF, for
      estimating the fetal DNA fraction in the plasma of pregnant women and to infer
      the underlying mechanism that allows for such statistical modeling. METHODS:
      Autosomal regional read counts from whole-genome massively parallel single-end
      sequencing of circulating cell-free DNA (ccfDNA) from the plasma of 25 312
      pregnant women were used to train a multivariate model. The pretrained model was
      then applied to 505 pregnant samples to assess the performance of SeqFF against
      known methodologies for fetal DNA fraction calculations. RESULTS: Pearson's
      correlation between chromosome Y and SeqFF for pregnancies with male fetuses from
      two independent cohorts ranged from 0.932 to 0.938. Comparison between a single
      nucleotide polymorphism-based approach and SeqFF yielded a Pearson's correlation
      of 0.921. Paired-end sequencing suggests that shorter ccfDNA, that is, less than
      150 bp in length, is nonuniformly distributed across the genome. Regions
      exhibiting an increased proportion of short ccfDNA, which are more likely of
      fetal origin, tend to provide more information in the SeqFF calculations.
      CONCLUSION: SeqFF is a robust and direct method to determine fetal DNA fraction.
      Furthermore, the method is applicable to both male and female pregnancies and can
      greatly improve the accuracy of noninvasive prenatal testing for fetal copy
      number variation.

PMID- 25967381
TI  - Predictors of delayed disclosure of rape in female adolescents and young adults.
AB  - BACKGROUND: Delayed disclosure of rape has been associated with impaired mental
      health; it is, therefore, important to understand which factors are associated
      with disclosure latency. The purpose of this study was to compare various
      demographics, post-rape characteristics, and psychological functioning of early
      and delayed disclosers (i.e., more than 1-week post-rape) among rape victims, and
      to determine predictors for delayed disclosure. METHODS: Data were collected
      using a structured interview and validated questionnaires in a sample of 323 help
      seeking female adolescents and young adults (12-25 years), who were victimized by
      rape, but had no reported prior chronic child sexual abuse. RESULTS: In 59% of
      the cases, disclosure occurred within 1 week. Delayed disclosers were less likely
      to use medical services and to report to the police than early disclosers. No
      significant differences were found between delayed and early disclosers in
      psychological functioning and time to seek professional help. The combination of
      age category 12-17 years [odds ratio (OR) 2.05, confidence intervals (CI) 1.13
      3.73], penetration (OR 2.36, CI 1.25-4.46), and closeness to assailant (OR 2.64,
      CI 1.52-4.60) contributed significantly to the prediction of delayed disclosure.
      CONCLUSION: The results point to the need of targeted interventions that
      specifically encourage rape victims to disclose early, thereby increasing options
      for access to health and police services.

PMID- 25967382
TI  - Pazopanib and pancreatic toxicity: a case report.
AB  - BACKGROUND: Pazopanib is an oral multitargeted tyrosine-kinase inhibitor, used as
      a single agent to treat advanced renal cell carcinoma. Treatment with other
      tyrosine-kinase inhibitors is known to be associated with asymptomatic elevations
      of serum amylase and lipase levels. As regards the pazopanib, data are lacking in
      literature. CASE PRESENTATION: We report one case of pancreatic toxicity
      associated with pazopanib administration. Before starting treatment, patient had
      no risk factors for pancreatitis. The patient, an Italian 68 years old woman,
      started pazopanib at doses of 800 mg daily as first-line therapy for metastatic
      renal cell carcinoma. Six months after the start of treatment, blood tests showed
      for the first time a significant increase in serum lipase and amylase in the
      absence of symptoms and radiological findings of pancreatitis. The patient
      continued treatment without interruptions or dose reductions. However, the
      continuation of the treatment led to a further increase of pancreatic enzymes. We
      tried to continue the treatment by reducing the dose but only the discontinuation
      was associated with normalization of amylase and lipase's levels. On the other
      hand the treatment with pazopanib got prolonged response of the disease in the
      absence of signs of pancreatitis. We therefore decided to continue treatment with
      pazopanib 400 mg daily with close monitoring of blood levels of pancreatic
      enzymes. CONCLUSIONS: We hypothesize that the increase of pancreatic enzymes is
      not a dose-dependent event. The mechanism for pancreatic toxicity induced by
      tyrosine-kinase inhibitors is unknown and no predictive factors have been
      identified. There are no clear guidelines on the management of the drug in the
      presence of pancreatic enzyme increase. In any case, we believe that a careful
      monitoring of pancreatic enzymes during treatment with pazopanib is advisable.

PMID- 25967383
TI  - Temporal Changes in Alcohol-Related Morbidity and Mortality in Germany.
AB  - AIMS: Trends in morbidity and mortality, fully or partially attributable to
      alcohol, for adults aged 18-64 were assessed for Germany. METHODS: The
      underestimation of population exposure was corrected by triangulating survey data
      with per capita consumption. Alcohol-attributable fractions by sex and two age
      groups were estimated for major disease categories causally linked to alcohol.
      Absolute numbers, population rates and proportions relative to all
      hospitalizations and deaths were calculated. RESULTS: Trends of 100% alcohol
      attributable morbidity and mortality over thirteen and eighteen years,
      respectively, show an increase in rates of hospitalizations and a decrease in
      mortality rates. Comparisons of alcohol-attributable morbidity including diseases
      partially caused by alcohol revealed an increase in hospitalization rates between
      2006 and 2012. The proportion of alcohol-attributable hospitalizations remained
      constant. Rates of alcohol-attributable mortality and the proportion among all
      deaths decreased. CONCLUSIONS: The increasing trend in mortality due to alcohol
      until the mid-1990s has reversed. The constant proportion of all hospitalizations
      that were attributable to alcohol indicates that factors such as improved
      treatment and easier health care access may have influenced the general increase
      in all-cause morbidity. To further reduce alcohol-related mortality, efforts in
      reducing consumption and increasing treatment utilization are needed.

PMID- 25967385
TI  - Whole exome sequencing reveals a novel de novo FOXC1 mutation in a patient with
      unrecognized Axenfeld-Rieger syndrome and glaucoma.
AB  - We report the identification of a novel mutation in the fork-head box C1 (FOXC1)
      gene which occurred de novo in an Italian patient with unrecognized Axenfeld
      Rieger syndrome. He was previously diagnosed as having late recognized primary
      congenital glaucoma at the age of 14 years and was subsequently subjected to
      multiple surgical interventions due to uncontrolled intraocular pressure and
      progressive visual field loss. After exclusion of mutations in CYP1B1 and MYOC,
      trio-whole-exome sequencing revealed de novo in frame deletion in the coding
      region of the FOXC1 gene (c.407_409delGTC, p.V137del) leading to a deletion of
      the evolutionary conserved amino acid Valine at position 137 of the protein.
      Molecular modeling predicted that Val137 deletion impairs FOXC1 DNA-binding
      capacity and transcriptional activation. Since loss-of-function mutations in
      FOXC1 are associated with Axenfeld-Rieger syndrome, the genetic findings in
      combination with re-evaluation of the patient's clinical data resulted in a
      corrected diagnosis of Axenfeld-Rieger syndrome with developmental glaucoma. We
      therefore suggest that in addition to CYP1B1 and MYOC, FOXC1 should be included
      in the genetic analysis of cases with unclear glaucomatous phenotypes to ensure
      proper diagnosis, adequate treatment and appropriate genetic counseling.

PMID- 25967384
TI  - Changes to the lateral geniculate nucleus in Alzheimer's disease but not dementia
      with Lewy bodies.
AB  - AIMS: Complex visual hallucinations occur in 70% of dementia with Lewy bodies
      (DLB) cases and significantly affect patient well-being. Visuo-cortical and
      retinal abnormalities have been recorded in DLB and may play a role in visual
      hallucinations. The present study aimed to investigate the lateral geniculate
      nucleus (LGN), a visual relay centre between the retina and visual cortex, to see
      if changes to this structure underlie visual hallucinations in DLB. METHODS:
      Fifty-one [17 probable DLB, 19 control and 15 probable Alzheimer's disease (AD)]
      cases were recruited for a functional magnetic resonance imaging study, in which
      patients' response to a flashing checkerboard stimulus was detected and measured
      in the LGN, before comparison across experimental groups. Additionally, post
      mortem LGN tissue was acquired for a cross-sectional study using 20 (six DLB,
      seven control and seven AD) cases and analysed using stereology. alpha-Synuclein,
      phosphorylated tau and amyloid-beta pathology was also assessed in all cases.
      RESULTS: DLB cases did not significantly differ from controls on neuroimaging,
      morphometry or pathology. However, a significant increase in amyloid-beta
      pathology, a reduction in number of parvocellular neurones and magnocellular
      gliosis was found in AD cases compared with control and DLB cases. CONCLUSIONS:
      These findings suggest that the early visual system is relatively spared in DLB,
      which implies that upstream visual structures may be largely responsible for the
      generation of hallucinatory percepts. The significance of the degeneration of the
      LGN in AD cases is uncertain.

PMID- 25967386
TI  - Variation in the ovine PRKAG3 gene.
AB  - The 5'AMP-activated protein kinase (AMPK) is a heterotrimeric enzyme that
      controls cellular energy homeostasis in response to environmental or nutritional
      stress. The PRKAG3 gene (PRKAG3) encodes the gamma3 subunit of the AMPK.
      Variation in this gene has been found to be associated with meat quality traits
      in pigs. In this study, we used polymerase chain reaction-single stranded
      conformational polymorphism (PCR-SSCP) to investigate variation in exon 3 and
      exons 4-6 of ovine PRKAG3. In 160 New Zealand Suffolk sheep, two variant
      sequences (named a and b) were identified in the exon 3 region of the gene and
      three variant sequences (named A, B and C) were identified in the exon 4-6 region
      of the gene, respectively. A total of three nucleotide substitutions were
      revealed and these were located in intron 4, exon 4 and intron 5, respectively.
      The nucleotide substitution identified in the exon 4 (g.2656 C>T) could nominally
      lead to an amino acid substitution of tryptophan to arginine at position 230
      (R230W) in ovine PRKAG3. In comparison with the PRKAG3 amino acid sequences in
      other species, this R230W substitution appeared to occur only in sheep. This is
      the first report of genetic variation in ovine PRKAG3, and the variation found in
      this study could be functionally important for AMPK activity, which in turn may
      affect meat quality traits in sheep.

PMID- 25967387
TI  - Genome-wide identification and analysis of the MADS-box gene family in sesame.
AB  - MADS-box genes encode transcription factors that play crucial roles in plant
      growth and development. Sesame (Sesamum indicum L.) is an oil crop that
      contributes to the daily oil and protein requirements of almost half of the
      world's population; therefore, a genome-wide analysis of the MADS-box gene family
      is needed. Fifty-seven MADS-box genes were identified from 14 linkage groups of
      the sesame genome. Analysis of phylogenetic relationships with Arabidopsis
      thaliana, Utricularia gibba and Solanum lycopersicum MADS-box genes was
      performed. Sesame MADS-box genes were clustered into four groups: 28 MIKC(c)
      type, 5 MIKC(*)-type, 14 Malpha-type and 10 Mgamma-type. Gene structure analysis
      revealed from 1 to 22 exons of sesame MADS-box genes. The number of exons in type
      II MADS-box genes greatly exceeded the number in type I genes. Motif distribution
      analysis of sesame MADS-box genes also indicated that type II MADS-box genes
      contained more motifs than type I genes. These results suggested that type II
      sesame MADS-box genes had more complex structures. By analyzing expression
      profiles of MADS-box genes in seven sesame transcriptomes, we determined that
      MIKC(C)-type MADS-box genes played significant roles in sesame flower and seed
      development. Although most MADS-box genes in the same clade showed similar
      expression features, some gene functions were diversified from the orthologous
      Arabidopsis genes. This research will contribute to uncovering the role of MADS
      box genes in sesame development.

PMID- 25967388
TI  - Association of tumor necrosis factor-alpha promoter G-308A gene polymorphism with
      increased triglyceride level of subjects with metabolic syndrome.
AB  - BACKGROUND: The G-308A single nucleotide polymorphism (SNP) in the promoter of
      tumor necrosis factor-alpha (TNF-alpha) gene has previously been reported to be
      associated with cardiovascular risk. However the potential association of this
      polymorphism with metabolic syndrome (MetS) is unclear. The aim of the current
      study was to explore the association of this TNF-alpha gene polymorphism with
      MetS in an Iranian population. METHODS/PATIENTS: Two hundred and twenty two
      subjects were recruited and anthropometric and biochemical parameters were
      determined. Genotyping was performed using the amplification refractory mutation
      system polymerase chain reaction. The association of the genetic-polymorphism
      with MetS was evaluated by univariate and multivariate analyses. RESULTS: MetS
      subjects had a significantly (P<0.05) higher level of fasted serum triglycerides,
      body-mass-index, waist-circumference, blood pressure and fasting-blood-glucose,
      and lower level of high-density lipoprotein cholesterol. The possession of AA or
      GA genotype of the TNF-alpha gene was not associated with MetS in our population.
      However the AA genotype of TNF-alpha was related to an increased level of
      triglyceride in MetS patients, compared to the control group. CONCLUSION: TNF
      alpha G-308A polymorphism is unlikely to play an important role in the
      development of MetS in our population.

PMID- 25967389
TI  - Peroxisomal D-bifunctional protein deficiency: First case reports from Slovakia.
AB  - D-bifunctional protein deficiency (#OMIM 261515) is a rare autosomal recessive
      hereditary metabolic disorder causing severe clinical and biochemical
      abnormalities that are usually fatal in the course of the first years of life.
      This disease is classified as single enzyme peroxisomal disorder affecting the
      beta-oxidation pathway in this compartment. In this paper we present a full
      overview of the clinical presentation, magnetic resonance imaging, biochemical
      and molecular data of two Slovak D-bifunctional protein deficient patients. In
      the clinical presentation of both patients severe generalized hypotonia,
      depression of neonatal reflexes, craniofacial dysmorphism and seizures dominated
      starting from the second day of life. In both patients, who died up to two years
      of life, we found elevated plasma levels of very long chain fatty acids and we
      identified the presence of causative mutations in the HSD17B4 gene. In the first
      case, we found the homozygous mutation c.46G>A, which is responsible for a defect
      in the dehydrogenase domain. In the second patient, the heterozygous mutations
      c.1369A>G and c.1516C>T were present and functionally they are related to the
      hydratase domain of the protein. This combination of mutations in the second
      patient is very rare and has not been reported until now. The presence of
      mutations was examined in all family members, and the resulting data were
      successfully utilized for prenatal diagnosis. 

PMID- 25967391
TI  - Visualization and tracking of tumour extracellular vesicle delivery and RNA
      translation using multiplexed reporters.
AB  - Accurate spatiotemporal assessment of extracellular vesicle (EV) delivery and
      cargo RNA translation requires specific and robust live-cell imaging
      technologies. Here we engineer optical reporters to label multiple EV populations
      for visualization and tracking of tumour EV release, uptake and exchange between
      cell populations both in culture and in vivo. Enhanced green fluorescence protein
      (EGFP) and tandem dimer Tomato (tdTomato) were fused at NH2-termini with a
      palmitoylation signal (PalmGFP, PalmtdTomato) for EV membrane labelling. To
      monitor EV-RNA cargo, transcripts encoding PalmtdTomato were tagged with MS2 RNA
      binding sequences and detected by co-expression of bacteriophage MS2 coat protein
      fused with EGFP. By multiplexing fluorescent and bioluminescent EV membrane
      reporters, we reveal the rapid dynamics of both EV uptake and translation of EV
      delivered cargo mRNAs in cancer cells that occurred within 1-hour post-horizontal
      transfer between cells. These studies confirm that EV-mediated communication is
      dynamic and multidirectional between cells with delivery of functional mRNA. 

PMID- 25967393
TI  - Fucofullerenes as tight ligands of RSL and LecB, two bacterial lectins.
AB  - A series of water-soluble glycofullerenes containing up to 24 fucose residues
      have been prepared. These compounds were tested against the two bacterial fucose
      binding lectins LecB and RSL, and C60(E)12 bearing 24 fucose residues appeared to
      be the best known inhibitor of both lectins to date. We have shown that
      increasing both the valency and the length of the spacer between the central core
      and the peripheral sugars can be beneficial for the affinity. 

PMID- 25967392
TI  - Cigarette smoking increases the risk of mortality from liver cancer: A clinical
      based cohort and meta-analysis.
AB  - BACKGROUND AND AIM: Although the influence of cigarette smoking on the incident
      risk of liver cancer has been determined, the association between smoking and
      liver cancer mortality remains uncertain. METHODS: We searched Pubmed, EmBase,
      and Web of Science databases to obtain eligible studies. Hazard ratio (HR) value
      and 95% confidential intervals (CI) were pooled by using a random-effects model,
      and dose-response analyses were conducted to quantify associations between
      smoking and mortality from liver cancer. RESULTS: A total of 27 articles
      involving four million participants from seven countries by retrieval (published
      1986-2014) were finally included. Pooled HR values for liver cancer mortality was
      1.45 (95% CI: 1.33-1.59), 1.22 (95% CI: 1.11-1.34) and 1.16 (95% CI: 1.01-1.32)
      for current, former, and ever smokers, respectively, when compared with
      nonsmokers. The risk increased by 7.1% (95% CI: 1.4-13.2) for per additional 10
      cigarettes per day and by 5.2% (95% CI: 0.02-11.2) for per additional 10 pack
      years. In our population recruiting 597 patients with liver cancer, smoking
      status was further identified as a significant determinant factor of tumor size
      and serum level of gamma-glutamyl transpeptidase, but not a significant
      prognostic factor. CONCLUSIONS: Cigarette smoking, especially current smoking,
      significantly increased mortality risk from liver cancer.

PMID- 25967394
TI  - Effect of UV-C light on the microbial and sensory quality of seasoned dried
      seafood.
AB  - This study investigated the effects of different doses of UV-C light at 253.7 nm
      (0-18 kJ/m(2)) on the reduction of Escherichia coli,Staphylococcus aureus and
      Bacillus cereus in contaminated seasoned dried filefish (Thamnaconus modestus)
      and sliced squid (Todarodes pacificus) surfaces and sensory quality. The counts
      of all three bacteria were significantly (P < 0.05) reduced by the increase of UV
      C dosage.E. coli,S. aureus and B. cereus on filefish with 18 kJ/m(2)of UV-C
      maximally reduced by 2.70, 2.55 and 2.57 log CFU/g, respectively; however, on the
      sliced squid using the same UV dose reduced the same bacteria by 1.35, 0.54 and
      1.05 log CFU/g, respectively. However, the results suggest that 6 to 9 kJ/m(2)of
      UV-C could be used for the inactivation of E. coli and B. cereus in these dried
      fishery products without any changes in sensory quality. However, S. aureus
      levels on sliced squid will require a combination of UV-C light and chemical
      treatment.

PMID- 25967395
TI  - Uncaging a catalytic hydrogen peroxide generator through the photo-induced
      release of nitric oxide from a {MnNO}(6) complex.
AB  - The photo-initiated cytotoxicity of a newly developed manganese nitrosyl
      {MnNO}(6) complex (UG1NO) to HeLa cells is described. The complex was found to be
      strongly cytotoxic after being exposed to light with a wavelength of 650 nm. Cell
      death was caused by a manganese(II) complex, UG1, generated from UG1NO through
      the photo-dissociation of NO, rather than by NO directly. Mechanistic studies
      revealed that UG1 consumes O2 only in the presence of a reducing agent to
      catalytically produce H2O2.

PMID- 25967390
TI  - Preclinical and clinical studies of the NEDD9 scaffold protein in cancer and
      other diseases.
AB  - Cancer progression requires a significant reprogramming of cellular signaling to
      support the essential tumor-specific processes that include hyperproliferation,
      invasion (for solid tumors) and survival of metastatic colonies. NEDD9 (also
      known as CasL and HEF1) encodes a multi-domain scaffolding protein that assembles
      signaling complexes regulating multiple cellular processes relevant to cancer.
      These include responsiveness to signals emanating from the T and B cell
      receptors, integrins, chemokine receptors, and receptor tyrosine kinases, as well
      as cytoplasmic oncogenes such as BCR-ABL and FAK- and SRC-family kinases.
      Downstream, NEDD9 regulation of partners including CRKL, WAVE, PI3K/AKT, ERK, E
      cadherin, Aurora-A (AURKA), HDAC6, and others allow NEDD9 to influence functions
      as pleiotropic as migration, invasion, survival, ciliary resorption, and mitosis.
      In this review, we summarize a growing body of preclinical and clinical data that
      indicate that while NEDD9 is itself non-oncogenic, changes in expression of NEDD9
      (most commonly elevation of expression) are common features of tumors, and
      directly impact tumor aggressiveness, metastasis, and response to at least some
      targeted agents inhibiting NEDD9-interacting proteins. These data strongly
      support the relevance of further development of NEDD9 as a biomarker for
      therapeutic resistance. Finally, we briefly discuss emerging evidence supporting
      involvement of NEDD9 in additional pathological conditions, including stroke and
      polycystic kidney disease. 

PMID- 25967396
TI  - Hair drug testing in the new Brazilian regulation to obtain professional driver's
      licence: no parallel to any other law enforcement in the world.

PMID- 25967397
TI  - A simple, high-yield synthesis of DNA duplexes containing a covalent, thermally
      cleavable interstrand cross-link at a defined location.
AB  - Interstrand DNA-DNA cross-links are highly toxic to cells because these lesions
      block the extraction of information from the genetic material. The pathways by
      which cells repair cross-links are important, but not well understood. The
      preparation of chemically well-defined cross-linked DNA substrates represents a
      significant challenge in the study of cross-link repair. Here a simple method is
      reported that employs "post-synthetic" modifications of commercially available 2'
      deoxyoligonucleotides to install a single cross-link in high yield at a specified
      location within a DNA duplex. The cross-linking process exploits the formation of
      a hydrazone between a non-natural N(4) -amino-2'-deoxycytidine nucleobase and the
      aldehyde residue of an abasic site in duplex DNA. The resulting cross-link is
      stable under physiological conditions, but can be readily dissociated and re
      formed through heating-cooling cycles. 

PMID- 25967400
TI  - Four issues that Mr Hunt should make top priority.

PMID- 25967398
TI  - Deficiency in the alpha1 subunit of Na+/K+-ATPase enhances the anti-proliferative
      effect of high osmolality in nucleus pulposus intervertebral disc cells.
AB  - Intervertebral disc cells are constantly exposed to a hyperosmotic environment.
      Among cellular responses towards this stress is the inhibition of proliferation
      through the activation of p38 MAPK and p53. In an effort to further elucidate the
      biochemical pathways triggered by hyperosmotic stress, we assessed the high
      osmolality-induced transcriptional changes of bovine nucleus pulposus cells using
      whole-genome arrays. A 5- and a 24-h hyperosmotic treatment led to the
      differential expression of >100 and >200 genes, respectively, including nine
      genes encoding transporters (SLC4A11, SLC5A3, ATP1A1, SLC38A2, KCNK17, KCTD20,
      KCTD11, SLC7A5, and CLCA2). Differences in the transcriptional profile of these
      selected genes, as indicated by the microarrays experiments, were validated by
      qRT-PCR in 2D and 3D cell cultures, under hyperosmolar salt and sorbitol
      conditions, revealing the presence of a common triggering signal for osmotic
      adaptation. The key signaling molecules p38 MAPK and p53 were demonstrated to
      differently participate in the regulation of the aforementioned transporters.
      Finally, siRNA-mediated knocking-down of each one of the three transporters with
      the highest and sustained over-expression (i.e., SLC4A11, SLC5A3, and ATP1A1) had
      a distinct outcome on the transcriptional profile of the other transporters, on
      p38 MAPK and p53 phosphorylation and consequently on cell cycle progression. The
      inhibition of ATP1A1 had the most prominent effect on the transcription of the
      rest of the transporters and was found to enhance the anti-proliferative effect
      of hyperosmotic conditions through an increased G2/M cell cycle block, ascribing
      to this pump a central role in the osmoregulatory response of nucleus pulposus
      cells.

PMID- 25967399
TI  - Use of information technology for medication management in residential care
      facilities: correlates of facility characteristics.
AB  - The effectiveness of information technology in resolving medication problems has
      been well documented. Long-term care settings such as residential care facilities
      (RCFs) may see the benefits of using such technologies in addressing the problem
      of medication errors among their resident population, who are usually older and
      have numerous chronic conditions. The aim of this study was two-fold: to examine
      the extent of use of Electronic Medication Management (EMM) in RCFs and to
      analyze the organizational factors associated with the use of EMM functionalities
      in RCFs. Data on RCFs were obtained from the 2010 National Survey of Residential
      Care Facilities. The association between facility, director and staff, and
      resident characteristics of RCFs and adoption of four EMM functionalities was
      assessed through multivariate logistic regression. The four EMM functionalities
      included were maintaining lists of medications, ordering for prescriptions,
      maintaining active medication allergy lists, and warning of drug interactions or
      contraindications. About 12% of the RCFs adopted all four EMM functionalities.
      Additionally, maintaining lists of medications had the highest adoption rate
      (34.5%), followed by maintaining active medication allergy lists (31.6%),
      ordering for prescriptions (19.7%), and warning of drug interactions or
      contraindications (17.9%). Facility size and ownership status were significantly
      associated with adoption of all four EMM functionalities. Medicaid certification
      status, facility director's age, education and license status, and the use of
      personal care aides in the RCF were significantly associated with the adoption of
      some of the EMM functionalities. EMM is expected to improve the quality of care
      and patient safety in long-term care facilities including RCFs. The extent of
      adoption of the four EMM functionalities is relatively low in RCFs. Some RCFs may
      strategize to use these functionalities to cater to the increasing demands from
      the market and also to provide better quality of care.

PMID- 25967401
TI  - Unions braced for a pay battle over the Tories' seven-day NHS pledge.

PMID- 25967402
TI  - Cancer research nurse joins the Commons.

PMID- 25967403
TI  - High rate of incidents reported for inpatients with learning disabilities.

PMID- 25967404
TI  - Call from a nurse quells patients' cancer anxiety.

PMID- 25967405
TI  - Trust strategy stresses taking pride in caring.

PMID- 25967406
TI  - Lamp lights way in 50th service.

PMID- 25967407
TI  - Many health staff lack training to carry out duty of candour effectively.

PMID- 25967409
TI  - NMC seeks midwives and nurses for fitness panels.

PMID- 25967410
TI  - UK near bottom of resourcing league.

PMID- 25967411
TI  - Universities urged to identify and advise nurses about revalidation.

PMID- 25967412
TI  - App helps parents teach children interaction skills.

PMID- 25967413
TI  - Coming out on top of the places to work for gay and bisexual people.

PMID- 25967419
TI  - Reducing tobacco use.

PMID- 25967420
TI  - The app that could save a child's life.

PMID- 25967421
TI  - When it comes to health, love is as good as it gets.

PMID- 25967422
TI  - Academy paves the way for new nurses.

PMID- 25967431
TI  - Carers Trust.

PMID- 25967434
TI  - iTriage.

PMID- 25967435
TI  - The NHS could struggle to survive five more years of Tory government.

PMID- 25967436
TI  - Unlike ours, most professional codes have an ethical dimension.

PMID- 25967437
TI  - If you thought it was a struggle before, the future looks bleaker.

PMID- 25967438
TI  - We believe it is better not to explicitly highlight spirituality.

PMID- 25967439
TI  - Continue to tell women about the warning signs of ovarian cancer.

PMID- 25967440
TI  - Apprenticeships give younger people entry into the profession.

PMID- 25967441
TI  - Where will revalidation fit into my already pressured worklife?

PMID- 25967444
TI  - Introduction to the dementia series.

PMID- 25967445
TI  - Dementia: definitions and types.
AB  - This article is the first in a series of articles on dementia and is intended as
      an introduction to the condition, discussing how it is defined and the different
      types of disease. Subsequent articles will discuss how dementia affects the
      brain, the clinical features of dementia, its assessment and diagnosis, and the
      medical management and treatment of dementia. The series will then look in depth
      at how nursing care can maximise the quality of life of those affected by
      dementia and their families. 

PMID- 25967446
TI  - Focus group research.
AB  - A focus group is usually understood as a group of people brought together by a
      researcher to interact as a group. Focus group research explicitly uses
      interaction as part of its methodology. This article summarises the practice of
      running focus groups, explores the nature of focus group data and provides an
      example of focus group analysis. 

PMID- 25967447
TI  - Crohn's disease in adolescence: presentation and treatment.
AB  - Crohn's disease is a chronic inflammatory bowel condition that affects more than
      115,000 people in the UK. This article focuses on Crohn's disease in adolescents.
      Management of the condition in this group should address adolescent-specific
      characteristics and treatment goals. Key elements include optimising growth,
      pubertal development and social functioning, including education. The condition
      can affect an individual's mental and emotional wellbeing significantly, as well
      as their physical health. As adolescence is a time of great change, the
      additional burden of a chronic illness can prove difficult to manage. The authors
      provide information on the presentation of Crohn's disease in adolescence and
      insights into the particular issues encountered by this group. 

PMID- 25967448
TI  - Asthma in older adults.

PMID- 25967449
TI  - Style and substance.

PMID- 25967451
TI  - Avoiding injury the Wanless way.

PMID- 25967452
TI  - Spotting great leadership.

PMID- 25967453
TI  - Care in a police cell.

PMID- 25967454
TI  - Circulating CD14(+)HLA-DR(-/low) myeloid-derived suppressor cell is an indicator
      of poor prognosis in patients with ESCC.
AB  - Accumulating evidences demonstrate that a population of suppressive cells known
      as myeloid-derived suppressor cells (MDSCs) is key immune modulators which
      suppress antitumor immunity. In this study, we found that the level of
      circulating CD14(+)HLA-DR(-/low) cells in patients was significantly higher than
      that of healthy donors and was correlated with tumor burden, lymph node
      metastasis, and tumor, node, and metastasis (TNM) clinical stage. More
      importantly, we for the first time find the level of CD14(+)HLA-DR(-/low) is a
      biological indicator of poor prognosis through the analysis of 3-year overall
      survival. Furthermore, we evidenced that the proportion of CD14(+)HLA-DR(-/low)
      cells in the tumor metastatic tumor-draining lymph nodes (TDLNs) was notably
      higher compared to tumor-free TDLNs. Additionally, CD14(+)HLA-DR(-/low) cells
      from esophageal squamous cell carcinoma (ESCC) patients expressed dramatically
      increased programmed death ligand 1 (PD-L1) comparing to that from healthy
      control. Subsequently, blocking PD-L1 pathway by antibody could effectively
      reverse the suppressive effect on autologous T cell proliferation mediated by
      CD14(+)HLA-DR(-/low) cells in vitro. In conclusion, our data revealed CD14(+)HLA
      DR(-/low) MDSCs which increase in ESCC patients is a novel poor prognostic
      indicator and may exert immunosuppressive properties through PD-L1/PD-1 pathway.

PMID- 25967455
TI  - High peritumoral Bmi-1 expression is an independent prognosticator of poor
      prognosis in renal cell carcinoma.
AB  - B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) is a transcriptional
      repressor, which plays important roles in the development of cancers, but the
      function of Bmi-1 in kidney tumorigenesis and its prognostic values remain
      unclear. This study aims to investigate prognostic values of the intratumoral and
      peritumoral expression of Bmi-1 in patients with renal cell carcinoma. Expression
      of Bmi-1 was assessed by immunohistochemistry in specimens containing paired
      tumor and peritumoral renal tissue from 241 patients who had undergone curative
      nephrectomy at Zhongshan Hospital from 2005 to 2007. The association of Bmi-1
      expression with clinical and pathological parameters and outcomes was
      investigated. Specific expression of Bmi-1 was found both in peritumoral and
      intratumoral tissues. High expression of Bmi-1 in peritumoral but not
      intratumoral is significantly associated with poor overall survival (OS) (P <
      0.001) and relapse-free survival (RFS) (P = 0.003). Furthermore, Bmi-1 expression
      was identified as an independent prognostic factor for OS, and combination of
      peritumoral Bmi-1 and tumor node metastasis (TNM) stage had a better power to
      predict the patients' death and disease recurrence. High peritumoral Bmi-1
      expression can serve as an independent prognostic biomarker and could be a novel
      therapeutic target for renal cell carcinoma (RCC).

PMID- 25967456
TI  - Downregulation of glypican-3 expression increases migration, invasion, and
      tumorigenicity of human ovarian cancer cells.
AB  - Glypican-3 (GPC3) is a membrane of heparan sulfate proteoglycan family involved
      in cell proliferation, adhesion, migration, invasion, and differentiation during
      the development of the majority of mesodermal tissues and organs. GPC3 is
      explored as a potential biomarker for hepatocellular carcinoma screening.
      However, as a tumor-associated antigen, its role in ovarian cancer remains
      elusive. In this report, the expression levels of GPC3 in the various ovarian
      cancer cells were determined with quantitative reverse transcription-polymerase
      chain reaction (qRT-PCR), and GPC3 expression in ovarian cancer UCI 101 and A2780
      cells was knocked down by siRNA transfection, and the effects of GPC3 knockdown
      on in vitro cell proliferation, migration, and invasion were respectively
      analyzed by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT)
      assay and Transwell migration assay. Additionally, the effect of GPC3 knockdown
      on in vivo tumorigenesis were investigated in athymic nude mice. The results
      indicated that GPC3 knockdown significantly promoted cell proliferation and
      increased cell migration and invasion by upregulation of matrix metalloproteinase
      (MMP)-2 and MMP-9 expression and downregulation of tissue inhibitor of
      metalloproteinase-1 expression. Additionally, GPC3 knockdown also increased in
      vivo tumorigenicity of UCI 101 and A2780 cells and final tumor weights and
      volumes after subcutaneous cell injection in the nude mice. The results of
      immunohistochemical staining and Western blotting both demonstrated a lower
      expression of GPC3 antigen in the tumors of GPC3 knockdown groups than that of
      negative control groups. Moreover, transforming growth factor-beta2 protein
      expression in the tumors of GPC3 knockdown groups was significantly increased,
      which at least contributed to tumor growth in the nude mice. Taken together,
      these findings suggest that GPC3 knockdown promotes the progression of human
      ovarian cancer cells by increasing their migration, invasion, and tumorigenicity,
      and suggest that GPC3 is a potential therapeutic target for ovarian cancer
      patients.

PMID- 25967457
TI  - MicroRNA-218 inhibits bladder cancer cell proliferation, migration, and invasion
      by targeting BMI-1.
AB  - MicroRNAs (miRNAs) are recognized as important molecules and have emerged as
      important gene regulators in tumorigenesis. Growing evidence suggested that miR
      218 was a tumor suppressor in many human cancers. However, its underlying role in
      bladder cancer (BCa) remains unclear. The aim of this study was to explore the
      effect of miR-218 on the proliferation, migration, and invasion of BCa cells. We
      found that miR-218 was frequently downregulated in BCa tissues compared with
      normal adjacent tissues. In vitro and in vivo assays demonstrated that miR-218
      overexpression in the BCa cells inhibited cell proliferation, migration, and
      invasion. Luciferase reporter assay showed that BMI-1 was a direct target of miR
      218. In addition, we found that miR-218 regulated the expression of BMI-1 and its
      downstream target (PTEN) and participated in the phosphorylation of AKT. Our
      findings indicate that miR-218 functions as tumor suppressor in BCa, and the miR
      218/BMI-1 axis may provide novel diagnostic and therapeutic strategies for the
      treatment of BCa.

PMID- 25967458
TI  - EMMPRIN in gynecologic cancers: pathologic and therapeutic aspects.
AB  - The highly glycosylated transmembrane protein extracellular matrix
      metalloproteinase inducer (EMMPRIN) is associated with several pathological
      conditions, including various types of cancers. In different gynecological
      malignancies, such as ovarian, cervical, and endometrial cancers, EMMPRIN plays
      significant roles in cell adhesion modulation, tumor growth, invasion,
      angiogenesis, and metastasis by inducing the production of various molecules,
      including matrix metalloproteinases and vascular endothelial growth factor.
      Because of its high level of expression, EMMPRIN can possibly be used as a
      diagnostic marker of gynecological cancers. Recent studies have showed that
      targeting EMMPRIN, especially by RNA interference (RNAi) technology, has
      promising therapeutic potential in basic research on gynecological cancer
      treatments, which make a platform for the future clinical success. This review
      study focused on the association of EMMPRIN in gynecological cancers in the
      perspectives of pathogenesis, diagnosis, and therapeutics. 

PMID- 25967459
TI  - Gastrointestinal endoscopy in the cirrhotic patient.
AB  - As advances in liver disease continue, including the increasing use of liver
      transplantation, the endoscopist needs to be familiar with the standards of care
      and potential complications in the management of the cirrhotic population. This
      includes both elective endoscopic procedures, such as screening colonoscopies and
      variceal banding, as well as the acutely bleeding cirrhotic patient. Peri
      procedural management and standards of care for acute gastrointestinal
      hemorrhaging of cirrhotic patients will be emphasized. This article will focus on
      the plethora of data available to highlight the benefits of endoscopic
      intervention in the care of patients with liver disease and outline the areas of
      future emphasis. 

PMID- 25967460
TI  - Gut microbes, immunity, and spondyloarthritis.
AB  - The last decade has witnessed an explosion of studies evaluating the impact of
      the human microbiota on a variety of disease states. The microbiota can impact
      diseases in multiple ways, including through abnormalities in the diversity and
      contents of the microbiota, as well as by acting as targets of immunologic
      dysregulation. Herein, evidence that the microbiota in spondyloarthritis is both
      altered and abnormally targeted by the immune system will be presented.

PMID- 25967461
TI  - The AVR2-SIX5 gene pair is required to activate I-2-mediated immunity in tomato.
AB  - Plant-invading microbes betray their presence to a plant by exposure of antigenic
      molecules such as small, secreted proteins called 'effectors'. In Fusarium
      oxysporum f. sp. lycopersici (Fol) we identified a pair of effector gene
      candidates, AVR2-SIX5, whose expression is controlled by a shared promoter. The
      pathogenicity of AVR2 and SIX5 Fol knockouts was assessed on susceptible and
      resistant tomato (Solanum lycopersicum) plants carrying I-2. The I-2 NB-LRR
      protein confers resistance to Fol races carrying AVR2. Like Avr2, Six5 was found
      to be required for full virulence on susceptible plants. Unexpectedly, each
      knockout could breach I-2-mediated disease resistance. So whereas Avr2 is
      sufficient to induce I-2-mediated cell death, Avr2 and Six5 are both required for
      resistance. Avr2 and Six5 interact in yeast two-hybrid assays as well as in
      planta. Six5 and Avr2 accumulate in xylem sap of plants infected with the
      reciprocal knockouts, showing that lack of I-2 activation is not due to a lack of
      Avr2 accumulation in the SIX5 mutant. The effector repertoire of a pathogen
      determines its host specificity and its ability to manipulate plant immunity. Our
      findings challenge an oversimplified interpretation of the gene-for-gene model by
      showing requirement of two fungal genes for immunity conferred by one resistance
      gene. 

PMID- 25967462
TI  - Effects of conventional neoadjuvant chemotherapy for breast cancer on tumor
      angiogenesis.
AB  - The effects of breast cancer conventional chemotherapy on tumor angiogenesis need
      to be further characterized. Neoadjuvant chemotherapy is an ideal model to
      evaluate the results of chemotherapy, allowing intra-patient direct comparison of
      antitumor and antiangiogenic effects. We sought to analyze the effect of
      neoadjuvant chemotherapy on tumor angiogenesis and its clinical significance in
      breast cancer. Breast cancer patients (n = 108) treated with neoadjuvant
      sequential anthracyclines and taxanes were studied. Pre- and post-chemotherapy
      microvessel density (MVD) and mean vessel size (MVS) were analyzed after CD34
      immunohistochemistry and correlated with tumor expression of pro- and
      antiangiogenic factors (VEGFA, THBS1, HIF1A, CTGF, and PDGFA) by qRT-PCR.
      Angiogenic measures at diagnosis varied among breast cancer subtypes. Pre
      treatment higher MVS was associated with triple-negative subtype and more
      advanced disease. Higher MVS was correlated with higher VEGFA (p = 0.003), while
      higher MVD was correlated with lower antiangiogenic factors expression (THBS1, p
      < 0.0001; CTGF, p = 0.001). Increased angiogenesis at diagnosis (high MVS and
      glomeruloid microvascular proliferation) and higher VEGFA expression were
      associated with tumor recurrence (p = 0.048 and 0.009, respectively).
      Chemotherapy-induced angiogenic response (defined as decreased MVD) was present
      in 35.2 % of patients. This response correlated with an increase in
      antiangiogenic factors (THBS1) without changes in VEGFA expression, and it was
      associated with tumor downstaging, but not with clinical response, pathologic
      complete response, or prognosis. Global effects of chemotherapy mainly consisted
      in an increased expression of antiangiogenic factors (THBS1, CTGF), with
      significant changes neither of tumor VEGFA nor of MVS. Conventionally scheduled
      neoadjuvant chemotherapy exerts antiangiogenic effects, through an increase in
      antiangiogenic factors, THBS1 and CTGF, but the expression of VEGFA is maintained
      after treatment. Better markers of angiogenic response and a better understanding
      of the cooperation of chemotherapy and antiangiogenic therapy in the neoadjuvant
      clinical scenario are needed. 

PMID- 25967463
TI  - Permanent ileostomy as the last surgical option for severe slow-transit
      constipation.

PMID- 25967464
TI  - Role of N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive
      protein, and inteleukin-6 in predicting a poor outcome after a stroke.
AB  - OBJECTIVE: N-terminal pro-B-type natriuretic peptide (NT-proBNP), high
      sensitivity C-reactive protein (hsCRP), and interleukin-6 (IL-6) concentrations
      can be important biomarkers in the acute stroke setting. In acute ischemic and
      hemorrhagic stroke patients, we investigated the association of NT-proBNP, hsCRP,
      and IL-6 serum concentrations with stroke severity and functional and cognitive
      outcomes at discharge. METHODS: Seventy-eight patients (53 men; median age 72
      years) admitted with ischemic or hemorrhagic stroke within 48 h of symptom onset
      were evaluated for clinical stroke severity (Scandinavian stroke scale; SSS),
      functional status before the stroke (modified Rankin scale; mRS), and
      cerebrovascular disease risk factors. Cognitive (Mini Mental State Examination)
      and functional (mRS) outcomes were evaluated at hospital discharge. Blood samples
      were drawn for the assessment of NT-proBNP, hsCRP, and IL-6 concentrations within
      24 h of admission. RESULTS: Greater NT-proBNP and hsCRP serum concentrations were
      associated with greater clinical stroke severity, adjusting for the patients'
      gender, age, stroke type, mRS score on admission, and presence of heart failure
      (beta = -0.292, p = 0.012; beta = -0.303, p = 0.009). In multivariate adjusted
      regression models with IL-6, hsCRP, and NT-proBNP considered together, IL-6 and
      hsCRP remained associated with worse functional (beta = 0.210, p = 0.022) and
      cognitive (beta = -0.269, p = 0.014) outcomes at discharge, respectively. In
      receiver operating characteristic analyses, the investigated blood biomarkers
      produced a minimal increase in predictive values for outcomes at discharge above
      the SSS score, age, and gender. CONCLUSIONS: In acute stroke patients, greater NT
      proBNP and hsCRP serum concentrations are independently associated with greater
      clinical stroke severity. Elevated concentrations of IL-6 and hsCRP are
      associated with worse functional and cognitive outcomes at discharge,
      respectively.

PMID- 25967465
TI  - A Novel Guide-Wire Technique for Repositioning a Nasobiliary Catheter from Mouth
      to Nostril without Using a Nelaton Tube.
AB  - OBJECTIVE: We aimed to assess the usefulness of a novel guide-wire technique for
      repositioning without the use of a Nelaton tube and to compare this to the
      conventional technique. SUBJECTS AND METHODS: A total of 50 patients who
      underwent endoscopic nasobiliary drainage (ENBD) at the Yachiyo Medical Center,
      Chiba, Japan, were enrolled into the study. The patients were randomly divided
      into 2 groups according to the use of a novel guide-wire technique (n = 28) or
      the conventional technique (n = 22). The ENBD catheters were repositioned from
      the mouth to the nose. The primary end point was the procedural time from the
      insertion of the Nelaton tube or guide wire into the nostril until the ENBD
      catheter had been repositioned in the nose. The secondary end point was the
      success rate of the procedure. RESULTS: The mean procedure time of our technique
      (120.8 s) was shorter than the traditional technique (131.9 s), but this
      difference was not statistically significant (p = 0.56). Our technique did not
      involve the use of the Nelaton tube, and so could save the cost of USD 1.17 per
      patient. The novel technique did not require the removal of the mouthpiece with a
      laryngoscope or the use of a Nelaton tube, and no postural change was necessary.
      A single operator performed the novel procedure unassisted. No adverse events
      were observed relating to either the novel or the traditional technique.
      CONCLUSIONS: The novel guide-wire technique for repositioning ENBD catheters was
      effective and is recommended for use.

PMID- 25967468
TI  - Animal posters.

PMID- 25967466
TI  - Determinants of family planning service uptake and use of contraceptives among
      postpartum women in rural Uganda.
AB  - OBJECTIVE: Uganda has one of the highest unmet needs for family planning
      globally, which is associated with negative health outcomes for women and
      population-level public health implications. The present cross-sectional study
      identified factors influencing family planning service uptake and contraceptive
      use among postpartum women in rural Uganda. METHODS: Participants were 258 women
      who attended antenatal care at a rural Ugandan hospital. We used logistic
      regression models in SPSS to identify determinants of family planning service
      uptake and contraceptive use postpartum. RESULTS: Statistically significant
      predictors of uptake of family planning services included: education (AOR = 3.03,
      95 % CI 1.57-5.83), prior use of contraceptives (AOR = 7.15, 95 % CI 1.58-32.37),
      partner communication about contraceptives (AOR = 1.80, 95 % CI 1.36-2.37), and
      perceived need of contraceptives (AOR = 2.57, 95 % CI 1.09-6.08). Statistically
      significant predictors of contraceptive use since delivery included: education
      (AOR = 2.04, 95 % CI 1.05-3.95), prior use of contraceptives (AOR = 10.79, 95 %
      CI 1.40-83.06), and partner communication about contraceptives (AOR = 1.81, 95 %
      CI 1.34-2.44). CONCLUSIONS: Education, partner communication, and perceived need
      of family planning are key determinants of postpartum family planning service
      uptake and contraceptive use, and should be considered in antenatal and postnatal
      family planning counseling.

PMID- 25967467
TI  - Disgrace at EU's external borders.

PMID- 25967469
TI  - Animal symposia.

PMID- 25967470
TI  - Joint symposia.

PMID- 25967471
TI  - Keynote symposium.

PMID- 25967473
TI  - Animal contributed papers.

PMID- 25967472
TI  - Plant symposia.

PMID- 25967474
TI  - Plant contributed papers.

PMID- 25967476
TI  - Plant posters.

PMID- 25967475
TI  - Education posters.

PMID- 25967478
TI  - Cloud deposition of PAHs at Mount Lushan in southern China.
AB  - Cloud water samples were collected from Mount Lushan, a high alpine area of
      southern China, and analyzed using GC-MS to investigate the concentration levels,
      seasonal variations, particle-dissolved phase partitioning, ecological risk of
      PAHs and its relationship to the atmosphere and rainwater. The average
      concentration of total (dissolved+particle) PAHs in cloud water was 819.90 ng/L,
      which ranged from 2.30 ng/L for DbA to 295.38 ng/L for PhA. PhA (33.11%)
      contributed the most individual PAHs, followed by Flu (28.24%). Distinct seasonal
      variations in the total PAHs measured in this research had a higher concentration
      during the spring and a lower concentration during the summer. When cloud events
      occurred, the concentration of the atmospheric PAHs of the two phases decreased.
      The contribution from the gaseous phase of total PAHs in the air to the dissolved
      phase in cloud water was up to 60.43%, but the particulate phase in the air only
      contributed 39.57% to the total scavenging. The contribution of total PAHs from
      the atmosphere to clouds is higher in the gaseous phase than in the particulate
      phase. A comparative study of the concentrations of cloud water and the closest
      rain water revealed that the PAH concentration in rainwater was 1.80 times less
      than that of cloud water and that the dominant individual compounds in cloud
      water and rainwater were PhA and Flu. A total of 81.27% of the PAHs in cloud
      samples and 72.21% of the PAHs in rain samples remained in the dissolved phase.
      Ecological risk assessment indicated that PAHs in cloud water in spring and
      summer caused a certain degree of ecosystem risk and the mean ecosystem risk in
      spring was higher than that in summer.

PMID- 25967479
TI  - Importance of environmental and biomass dynamics in predicting chemical exposure
      in ecological risk assessment.
AB  - In ecological risk assessment, exposure is generally modelled assuming static
      conditions, herewith neglecting the potential role of emission, environmental and
      biomass dynamics in affecting bioavailable concentrations. In order to
      investigate the influence of such dynamics on predicted bioavailable
      concentrations, the spatially-resolved dynamic model "ChimERA fate" was
      developed, incorporating macrophyte and particulate/dissolved organic carbon
      (POC/DOC) dynamics into a water-sediment system. An evaluation against three case
      studies revealed a satisfying model performance. Illustrative simulations then
      highlighted the potential spatio-temporal variability of bioavailable
      concentrations after a pulsed emission of four chemicals in a system composed of
      a pond connected to its inflow and outflow streams. Changes in macrophyte biomass
      and POC/DOC levels caused exposure variations which were up to a factor of 4.5 in
      time and even more significant (several orders of magnitude) in space, especially
      for highly hydrophobic chemicals. ChimERA fate thus revealed to be a useful tool
      to investigate such variations and to identify those environmental and ecological
      conditions in which risk is expected to be highest. 

PMID- 25967480
TI  - Recognizing different impacts of human and natural sources on the spatial
      distribution and temporal trends of PAHs and PCBs (including PCB-11) in sediments
      of the Nador Lagoon (Morocco).
AB  - The Nador Lagoon holds a major interest in present-day Moroccan socioeconomic
      development. This environment is exposed to a number of potential polluting
      sources, such as mine tailings, urban and industrial dumping, and untreated
      wastewater inputs from surrounding cities. The aim of this study was to assess
      concentrations and trends of persistent contaminants such as PCBs and PAHs and to
      identify their origin. The non-Aroclor PCB-11 was determined for the first time
      in the lagoon sediments. Chronology and source assessment helped identifying the
      timing and nature of inputs and post-depositional processes controlling the two
      classes of contaminants: PAHs present a typical mixed petrogenic signature, with
      the exception of sediments deposited in the period 1930-1960 near the city of
      Nador, when pyrogenic inputs prevailed; PCBs show signs of microbial anaerobic
      degradation from 1950 to 1990, probably linked to changing hydrodynamic
      conditions in the South-Western part of the lagoon where agricultural inputs are
      dominant. The presence of PCB-11 is linked to specific productions and might be
      affected by degradation processes. Presently, different land uses (e.g., urban
      and agricultural areas) appear to be the key factors in controlling the level and
      composition of PAHs and PCBs in lagoon sediments. Total PAH and PCB levels are
      low (from 21.6 to 108 ng g(-1) and from 2.50 to 20.7 ng g(-1), respectively) but
      recent increasing values and the potential threat to humans and biota require
      continuous and constant monitoring.

PMID- 25967481
TI  - Single- and dual-wavelength switchable linear polarized Yb(3+)-doped double-clad
      fiber laser.
AB  - A single- and dual-wavelength switchable linear polarized Yb-doped double-clad
      fiber laser is proposed, in which the resonance cavity was composed of a fiber
      Bragg grating fabricated in a polarization-maintaining fiber and a dichromatic
      mirror with high reflectivity. The polarization hole burning is enhanced through
      selective polarization feedback by the polarization-maintaining fiber Bragg
      grating. The switchover of single and dual wavelengths is realized by tuning the
      rotation angle of a cubic polarization beam splitter that is inserted between the
      dichromatic mirror and the collimator in the cavity. The laser features
      wavelengths of 1070.08 and 1070.39 nm, output power of 1.0 W, signal to noise
      ratio of 45 dB, and slope efficiency of 34%, as well as a very narrow linewidth
      of 0.022 nm. The polarization characteristics are analyzed by measuring the laser
      power transmitted through a Glan-Thomson polarizer during rotation.

PMID- 25967482
TI  - High-precision system identification method for a deformable mirror in wavefront
      control.
AB  - Based on a mathematic model, the relation between the accuracy of the influence
      matrix and the performance of the wavefront correction is established. Based on
      the least squares method, a two-step system identification is proposed to improve
      the accuracy of the influence matrix, where the measurement noise can be
      suppressed and the nonlinearity of the deformable mirror can be compensated. The
      validity of the two-step system identification method is tested in the
      experiment, where improvements in wavefront correction precision as well as
      closed-loop control efficiency were observed.

PMID- 25967483
TI  - Near-field enhancement of the nanostructure on the fused silica with rigorous
      method.
AB  - A rigorous electromagnetic method is developed to analyze the resonance effect of
      near field caused by nanoscale subsurface defects, which play a key role in
      describing absorption enhancement during laser-matter interaction for transparent
      dielectric materials. The total electric field calculated with this new method is
      consistent with the result of finite-difference time-domain simulation. The
      concept of mode amplitude density spectrum is developed to analyze the specific
      modes of the total field. A new mode parameter is proposed to demarcate the
      contribution of the resonance. The frequency space is divided into four parts and
      the resonance effect is analyzed as well as the contributions of different modes
      to the total field. The influence of the structure parameters on the near-field
      modulation and energy transference is also discussed. It is found that the
      enhancement mechanism of the near-field and local absorption is the resonance
      effect caused by the total internal reflection on the sidewall of the
      nanostructure. In addition, the surrounding energy is mainly guided into the
      structure by the root of the structure via the energy flow analysis.

PMID- 25967484
TI  - Ultracompact tapered coupler for the Si/III-V heterogeneous integration.
AB  - An ultracompact tapered coupler, which is suitable for mode transformation
      between a 220 nm high silicon wire waveguide and a Si/III-V hybrid waveguide, is
      proposed for Si/III-V heterogeneous integration. The tapered coupler is composed
      of three sections. Since the tapered coupler avoids exciting the unwanted high
      order modes in the III-V waveguide, the length of the tapered coupler can be
      dramatically shortened. In the proposed structure, the total length of the
      trisectional tapered coupler can be as short as 8 MUm with a fundamental mode
      coupling efficiency of over 95% in a bandwidth of over 100 nm. The alignment
      tolerance of the proposed structure is also analyzed.

PMID- 25967485
TI  - Passively Q-switched mode-locking of Tm:YAP laser based on Cr:ZnS saturable
      absorber.
AB  - Using a Cr:ZnS wafer as the saturable absorber, diode-pumped passively Q-switched
      mode-locking of a Tm:YAP laser at 1976 nm has been realized for the first time,
      to the best of our knowledge, and nearly 100% modulation depth of Q-switched mode
      locking was achieved. The width of the mode-locked pulse was estimated to be
      about 980 ps with a repetition rate of 350 MHz within a roughly 300-ns-long Q
      switched pulse envelope. A maximum output power of 940 mW was obtained,
      corresponding to the Q-switched pulse energy of 0.55 mJ. The emission wavelength
      evolution between the continuous-wave and Q-switched mode-locked operations was
      presented and discussed. The experimental results indicate that the Cr:ZnS
      absorber is a promising saturable absorber for passively Q-switched mode-locking
      operation around 2 MUm.

PMID- 25967486
TI  - Deconvolution methods based on phiHL regularization for spectral recovery.
AB  - The recorded spectra often suffer noise and band overlapping, and deconvolution
      methods are always used for spectral recovery. However, during the process of
      spectral recovery, the details cannot always be preserved. To solve this problem,
      two regularization terms are introduced and proposed. First, the conditions on
      the regularization term are analyzed for smoothing noise and preserving detail,
      and according to these conditions, phiHL regularization is introduced into the
      spectral deconvolution model. In view of the deficiency of phiHL under noisy
      condition, adaptive phiHL regularization (phiAHL) is proposed. Then semi-blind
      deconvolution methods based on phiHL regularization (SBD-HL) and based on
      adaptive phiHL regularization (SBD-AHL) are proposed, respectively. The
      simulation experimental results indicate that the proposed SBD-HL and SBD-AHL
      methods have better recovery, and SBD-AHL is superior to SBD-HL, especially in
      the noisy case.

PMID- 25967487
TI  - Markov chain Monte Carlo sampling based terahertz holography image denoising.
AB  - Terahertz digital holography has attracted much attention in recent years. This
      technology combines the strong transmittance of terahertz and the unique features
      of digital holography. Nonetheless, the low clearness of the images captured has
      hampered the popularization of this imaging technique. In this paper, we perform
      a digital image denoising technique on our multiframe superposed images. The
      noise suppression model is concluded as Bayesian least squares estimation and is
      solved with Markov chain Monte Carlo (MCMC) sampling. In this algorithm, a
      weighted mean filter with a Gaussian kernel is first applied to the noisy image,
      and then by nonlinear contrast transform, the contrast of the image is restored
      to the former level. By randomly walking on the preprocessed image, the MCMC
      based filter keeps collecting samples, assigning them weights by similarity
      assessment, and constructs multiple sample sequences. Finally, these sequences
      are used to estimate the value of each pixel. Our algorithm shares some good
      qualities with nonlocal means filtering and the algorithm based on conditional
      sampling proposed by Wong et al. [Opt. Express18, 8338
      (2010)10.1364/OE.18.008338OPEXFF1094-4087], such as good uniformity, and,
      moreover, reveals better performance in structure preservation, as shown in
      numerical comparison using the structural similarity index measurement and the
      peak signal-to-noise ratio.

PMID- 25967488
TI  - Extremely high-power CO2 laser beam correction.
AB  - This paper presents the results of high-power CO2 laser-aberration correction and
      jitter stabilization. A bimorph deformable mirror and two tip-tilt piezo
      correctors were used as executive elements. Two types of wavefront sensors, one
      Hartmann to measure higher-order aberrations (defocus, astigmatism etc.) based on
      an uncooled microbolometer long-wave infrared camera and the other a tip-tilt one
      based on the technology of obliquely sputtered, thin chromium films on Si
      substrates, were applied to measure wavefront aberrations. We discuss both
      positive and negative attributes of suggested wavefront sensors. The adaptive
      system is allowed to reduce aberrations of incoming laser radiation by seven
      times peak-to-valley and to stabilize the jitter of incoming beams up to 25 MUrad
      at a speed of 100 Hz. The adaptive system frequency range for high-order
      aberration correction was 50 Hz.

PMID- 25967489
TI  - All-optical cryptography of M-QAM formats by using two-dimensional spectrally
      sliced keys.
AB  - There has been an increased interest in enhancing the security of optical
      communications systems and networks. All-optical cryptography methods have been
      considered as an alternative to electronic data encryption. In this paper we
      propose and verify the use of a novel all-optical scheme based on cryptographic
      keys applied on the spectral signal for encryption of the M-QAM modulated data
      with bit rates of up to 200 gigabits per second. 

PMID- 25967491
TI  - Theoretical and experimental investigation of singly resonant optical parametric
      oscillator under double-pass pumping.
AB  - The singly resonant optical parametric oscillator (SRO) under double-pass pumping
      in a two-mirror linear cavity is investigated theoretically and experimentally.
      Different output couplers are used in the periodically poled lithium niobate
      based SRO to optimize the extracted signal output. When the 2.5% output coupler
      is used, a pump threshold as low as 3.7 W is achieved, and 6.2 W of signal at
      1.56 MUm with the linewidth of 62.5 kHz is obtained at pump power of 14.5 W. The
      measured signal frequency drift and peak-to-peak power fluctuation are less than
      +/-40 MHz and +/-0.9% in a given 1 h, respectively.

PMID- 25967490
TI  - Thin-film a-Si:H solar cells processed on aluminum-induced texture (AIT) glass
      superstrates: prediction of light absorption enhancement.
AB  - Light scattering superstrates are important for thin-film a-Si:H solar cells. In
      this work, aluminum-induced texture (AIT) glass, covered with nonetched Al-doped
      ZnO (AZO), is investigated as an alternative to the commonly used planar glass
      with texture-etched AZO superstrate. Four different AIT glasses with different
      surface roughnesses and different lateral feature sizes are investigated for
      their effects on light trapping in a-Si:H solar cells. For comparison, two
      reference superstrates are investigated as well: planar glass covered with
      nonetched AZO and planar glass covered with texture-etched AZO. Single-junction a
      Si:H solar cells are deposited onto each superstrate, and the scattering
      properties (haze and angular resolved scattering) as well as the solar cell
      characteristics (current-voltage and external quantum efficiency) are measured
      and compared. The results indicate that AIT glass superstrates with nonetched AZO
      provide similar, or even superior, light trapping than the standard reference
      superstrate, which is demonstrated by a higher short-circuit current Jsc and a
      higher external quantum efficiency. Using the trapped light fraction delta, a
      quantity based on the integrated light scattering at the AZO/a-Si:H interface, we
      show that Jsc linearly increases with delta in the scattering regime of the
      samples, regardless of the type of superstrate used.

PMID- 25967492
TI  - Photonic generation of polarization-resolved wideband chaos with time-delay
      concealment in three-cascaded vertical-cavity surface-emitting lasers.
AB  - Optical chaos generated by chaotic lasers has been widely used in several
      important applications, such as chaos-based communications and high-speed random
      number generators. However, these applications are susceptible to degradation by
      the presence of time-delay (TD) signature identified from the chaotic output.
      Here we propose to achieve the concealment of TD signature, along with the
      enhancement of chaos bandwidth, in three-cascaded vertical-cavity surface
      emitting lasers (VCSELs). The cascaded system is composed of an external-cavity
      master VCSEL, a solitary intermediate VCSEL, and a solitary slave VCSEL. Through
      mapping the evolutions of TD signature and chaos bandwidth in the parameter space
      of the injection strength and frequency detuning, photonic generation of
      polarization-resolved wideband chaos with TD concealment is numerically
      demonstrated for wide regions of the injection parameters. 

PMID- 25967493
TI  - Tight focus of light using micropolarizer and microlens.
AB  - Using a binary microlens of diameter 14 MUm and focal length 532 nm (NA=0.997) in
      resist, we focus a 633 nm laser beam into a near-circular focal spot with
      dimensions (0.35 +/- 0.02)lambda and (0.38 +/- 0.02)lambda (lambda is incident
      wavelength) at full width half-maximum intensity. The area of the focal spot is
      0.105lambda(2). The incident light is a mixture of linearly and radially
      polarized beams generated by reflecting a linearly polarized Gaussian beam at a
      100  MUm * 100  MUm four-sector subwavelength diffractive optical microelement
      with a gold coating. The focusing of a linearly polarized laser beam (the other
      conditions being the same) is found to produce an elliptical focal spot measuring
      (0.40 +/- 0.02)lambda and (0.50 +/- 0.02)lambda. To our knowledge, this is the
      first implementation of subwavelength focusing of light using a pair of micro
      optic elements (a binary microlens and a micropolarizer).

PMID- 25967494
TI  - Wave transfer matrix for a spiral phase plate.
AB  - The wave transfer matrix (WTM) is applied to calculating various characteristics
      of a spiral phase plate (SPP) for the first time to our knowledge. This approach
      provides a more convenient and systematic approach to calculating properties of a
      multilayered SPP device. In particular, it predicts the optical wave
      characteristics on the input and output plane of the device when the SPP is
      fabricated on a substrate of the same refractive index as the SPP as well as on a
      substrate of a different refractive index compared to the SPP. The dependence of
      the parameters on the input laser frequency is studied in detail for a low
      finesse SPP etalon device for both cases. The equations derived from the WTM are
      used to show that a variation in input laser frequency causes the optical
      intensity pattern on the output plane to rotate, while preserving the topology of
      the optical vortex, i.e., the variation in laser frequency has a minimal effect
      on the parameters describing the azimuthal intensity modulation and orbital
      angular momentum content of the beam. In addition, the equations predict the
      presence of longitudinal modes in the SPP device. 

PMID- 25967495
TI  - Simultaneous optimization method for absorption spectroscopy postprocessing.
AB  - A simultaneous optimization method is proposed for absorption spectroscopy
      postprocessing. This method is particularly useful for thermometry measurements
      based on congested spectra, as commonly encountered in combustion applications of
      H2O absorption spectroscopy. A comparison test demonstrated that the simultaneous
      optimization method had greater accuracy, greater precision, and was more user
      independent than the common step-wise postprocessing method previously used by
      the authors. The simultaneous optimization method was also used to process
      experimental data from an environmental chamber and a constant volume combustion
      chamber, producing results with errors on the order of only 1%.

PMID- 25967496
TI  - Research of two-dimensional beam steering in LCOS-based wavelength selective
      switch.
AB  - The phenomenon of two-dimensional beam steering in liquid crystal on silicon
      (LCOS) is demonstrated. We propose a novel flexible wavelength selective switch
      (WSS) using LCOS two-dimensional beam steering. The cross talk of adjacent
      channel in the WSS is theoretically small, while the measured insert loss is
      lower than 15 dB.

PMID- 25967497
TI  - Line shape of amplitude or frequency-modulated spectral profiles including
      resonator distortions.
AB  - We report experiments and an improved method of analysis for any harmonics of
      frequency-modulated spectral line shapes allowing for very precise determinations
      of the resonance frequency of single absorption lines for gigahertz spectroscopy
      in the gas phase. Resonator perturbations are implemented into the formalism of
      modulation spectroscopy by means of a full complex transmission function being
      able to model the asymmetrically distorted absorption line shapes for arbitrary
      modulation depths, modulation frequencies, and resonator reflectivities. Exact
      equations of the in-phase and the quadrature modulation signal, taking into
      account a full resonator transmission function, are simultaneously adjusted to
      two-channel lock-in measurements performed in the gigahertz regime to obtain the
      spectral line position. The determination of the absorption line position of the
      rotational transition J' = 7 <- J" = 6 of (16)O(12)C(32)S in the vibrational
      ground state is investigated while changing the resonator distortions. The
      results are subjected to the approach proposed here and compared to standard
      methods known from the literature.

PMID- 25967498
TI  - Efficient line-based lens distortion correction for complete distortion with
      vanishing point constraint.
AB  - The line-based correction method has been widely researched to improve the
      performance of lens distortion correction. However, due to the coupling of the
      distortion parameters and the inaccuracy of line equation estimation, it is
      difficult to achieve high-accuracy correction under the complete lens distortion
      (composed of radial, decentering, and prism distortion). Here, we present a
      method that utilizes two models to resolve these two problems, respectively: the
      recursive individual optimization model decouples the distortion parameters by
      applying Levenberg-Marquardt to optimize the parameters individually, and the
      vanishing point reprojection model improves the accuracy of line equation
      estimation with the known vanishing points calculated by a proposed expectation
      minimization algorithm. Therefore, accurate correction of complete distortion can
      be achieved by the line information only. The validity of the proposed method was
      tested by several synthetic and real data, and the results showed that this
      method can correct the image with the complete and noncomplete distortion
      effectively. 

PMID- 25967499
TI  - Detection of aromatic compounds in tequila through the use of surface plasmon
      resonance.
AB  - For an expert nose, the aroma of a beverage is a fingerprint that can be used to
      certify its authenticity, distinguish between distillation processes, or even
      identify the raw material used to fabricate it. In this work, we propose a
      simple, automatic, and repeatable optical method, which can be used as a first
      and quick test to authenticate tequila samples. This method is based on the
      measurement of beam intensity changes, using the surface plasmon resonance
      technique, operating at a fixed angle. We observed that each tequila, depending
      on the alcohol content and aging process, produces a specific change in measured
      intensity level. 

PMID- 25967500
TI  - High-axial-resolution, full-field optical coherence microscopy using tungsten
      halogen lamp and liquid-crystal-based achromatic phase shifter.
AB  - A high-axial-resolution, full-field optical coherence microscope (FFOCM) for
      topography and tomography applications is presented. The FFOCM is based on a
      polarization Linnik interference microscope equipped with a tungsten halogen
      lamp. The phase difference between the reference and test beams in the microscope
      is precisely and quickly shifted by using an achromatic liquid-crystal phase
      shifter (LCPS). The cross-sectional amplitude and phase maps of an interferogram
      are retrieved by using a three-step phase-shifting technique. The LCPS consists
      of three identical nematic liquid-crystal (NLC) cells sandwiched between two
      quarter-wave plates so that it functions as a typical quarter-half-quarter phase
      shifter. Instead of using high-cost NLC cells with precise thickness of half-wave
      retardation, a method is proposed to operate thicker NLC cells without scarifying
      the axial resolution. Experimental results reveal that the FFOCM is able to
      perform three-dimensional micrometer-resolution imaging. 

PMID- 25967501
TI  - Qualitative evaluation of Pb and Cu in fish using laser-induced breakdown
      spectroscopy with multipulse excitation by ultracompact laser source.
AB  - We show a new laser-induced breakdown spectroscopy (LIBS) setup based on a small,
      ultracompact, and low-cost excitation source developed by the authors. The laser
      is a compact Nd:YAG laser emitting in the multipulse Q-switch regime and is
      capable of delivering a bunch of pulses with a total energy up to 300 mJ. The
      developed system is applied to the analysis of Pb and Cu contaminants on fish.
      LIBS spectra were obtained from scales, muscle, and skin of fresh and frozen
      samples. The developed excitation source is able to detect 0.25 mg/Kg and 0.20
      mg/Kg of Pb and Cu, respectively. In this way, the equipment seems to be adequate
      to achieve a screening analysis of those contaminants.

PMID- 25967502
TI  - Linear polarization optimized Stokes polarimeter based on four-quadrant detector.
AB  - A four-quadrant detector (4QD) consists of four well-balanced detectors. We
      report on a Stokes polarimeter with optimal linear polarization measurements
      based on a 4QD. We turned the four intensity-detection channels into four
      polarization-analyzing channels by placing four polarizers and one quarter-wave
      plate in front of the individual detectors. An optimization method for the four
      polarization-analyzing channels is proposed to improve measurement accuracy.
      Considering applications in favor of linear polarization measurements instead of
      global optimization for all the possible states of polarization (SOP), we
      optimize the polarimeter first for the linear polarization components and then
      for the circular polarization component. The polarimeter is capable of
      simultaneous measurements of fast varying SOP with improved performance for the
      linear polarizations.

PMID- 25967503
TI  - Investigating the characteristics of TM-pass/TE-stop polarizer designed using
      plasmonic nanostructures.
AB  - Plasmonics-based polarizers are important for many photonic devices and
      applications. In this paper, we design and investigate the characteristics of a
      new TM-pass/TE-stop polarizer using silver nanograting of exponentially tapered
      slit sidewalls. Performance of the designed polarizer is determined through
      monitoring the modification of its insertion loss, return loss, extinction ratio,
      and far-field transform due to changing its structural parameters. We find that
      the structural parameters of the reported polarizer such as a slit sidewall
      tapering coefficient and slit opening widths have a significant impact on tuning
      the polarizer characteristics.

PMID- 25967504
TI  - All-optical logic operation of polarized light signals in highly nonlinear
      silicon hybrid plasmonic microring resonators.
AB  - All-optical logic operation is theoretically demonstrated by means of
      polarization-dependent four-wave mixing (FWM) processes in a highly nonlinear
      silicon hybrid plasmonic waveguide (HPWG) microring resonator. We design an ultra
      compact (radii = 1 MUm) microring resonator (MRR) that is realized by using a
      silicon HPWG with the capacity for subwavelength-bending. The HPWG exhibits very
      high confinement (Aeff~0.045 MUm(2)) that can result in a remarkably high
      nonlinear parameter (gamma~3000 W(-1) m(-1)), given a highly nonlinear gap
      material. By manipulating the polarization properties of the pump and signals
      with a very low electric field (|E|~10(8) Vm(-1)), all-optical NOT, NOR, and NAND
      logical operations are obtained through the FWM process. These compact all
      optical nanoplasmonic devices are stable, fabrication simplified, and silicon on
      insulator (SOI) compatible.

PMID- 25967505
TI  - Quantitative photothermal phase imaging of red blood cells using digital
      holographic photothermal microscope.
AB  - Photothermal microscopy (PTM), a noninvasive pump-probe high-resolution
      microscopy, has been applied as a bioimaging tool in many biomedical studies. PTM
      utilizes a conventional phase contrast microscope to obtain highly resolved
      photothermal images. However, phase information cannot be extracted from these
      photothermal images, as they are not quantitative. Moreover, the problem of halos
      inherent in conventional phase contrast microscopy needs to be tackled. Hence, a
      digital holographic photothermal microscopy technique is proposed as a solution
      to obtain quantitative phase images. The proposed technique is demonstrated by
      extracting phase values of red blood cells from their photothermal images. These
      phase values can potentially be used to determine the temperature distribution of
      the photothermal images, which is an important study in live cell monitoring
      applications. 

PMID- 25967506
TI  - Simulation design of a wearable see-through retinal projector.
AB  - This study proposes a new simulation design for a wearable see-through retinal
      projector combined with a compact camera. The see-through retinal projector is
      composed of an illumination system and eyepiece system. In this eyeglass-mounted
      design, all the information is projected directly into the user's eyes using a
      see-through retinal projector. The retinal projector forms a 20 in. (50.8 cm)
      upright virtual image located 2 m in front of the human eye, and the illumination
      system provides uniform illumination for liquid crystal on silicon (LCoS) panels.
      Moreover, an RGB LED array is used as the light source to generate color images
      with color sequences. The compact camera has a lens with an aperture of F/2.8, a
      half field-of-view (FOV) of 30 degrees , and 2 million pixels. This optical
      system design with the combination of a see-through retinal projector and a
      compact camera has a volume of about 5.83 cm(3) and a weight of 6.02 g.

PMID- 25967507
TI  - Terahertz spectroscopic identification of explosive and drug simulants concealed
      by various hiding techniques.
AB  - Terahertz time-domain spectroscopy and imaging is used to study the effects of
      various hiding techniques of spectral features of drug and explosive simulants in
      combination with different paper and textile barriers. Results show that rapid
      detection and identification of concealed simulants is possible in the frequency
      range from 1.5 to 4.0 THz by using an organic-crystal-based terahertz time-domain
      system and the spectral peak analysis method.

PMID- 25967508
TI  - Hybrid method of free-form lens design for arbitrary illumination target.
AB  - We propose a hybrid method of free-form illumination design for an arbitrary
      target form, imposing no restriction on the boundary of the irradiance
      distribution. Smooth continuous surfaces and continuous irradiance distributions
      are achieved with two independent steps. Initial solutions of the illumination
      problem are obtained with the method of supporting paraboloids, and final
      solutions are acquired by numerically solving the elliptic Monge-Ampere
      equations. Lenses, which are able to produce complex irradiance distributions,
      can be achieved with this method and fabricated in practice. The feasibility of
      this approach is demonstrated by some examples with experimental results. 

PMID- 25967509
TI  - Experimental demonstration of polarization-division multiplexing of chaotic laser
      secure communications.
AB  - Optical polarization-division multiplexing (PDM) can double the capacity of a
      communication system. In this paper, PDM between a conventional fiber-optic
      channel and a chaos-encrypted channel, and between two chaos-encrypted channels,
      is proposed and experimentally investigated. The bit rate for each channel is
      1.25 Gb/s, while the transmission in the standard single-mode fiber can be up to
      22.54 km. The effect of the mutual power leakages on the receiver quality is
      experimentally explored, which is induced by the variation in polarization
      direction during the propagating process. In addition, the effect of optical
      launched power at the transmitter side on the Q-factor is tested and analyzed.

PMID- 25967510
TI  - Image registration under translation and rotation in two-dimensional planes using
      Fourier slice theorem.
AB  - Image recognition in the presence of both rotation and translation is a
      longstanding problem in correlation pattern recognition. Use of log polar
      transform gives a solution to this problem, but at a cost of losing the vital
      phase information from the image. The main objective of this paper is to develop
      an algorithm based on Fourier slice theorem for measuring the simultaneous
      rotation and translation of an object in a 2D plane. The algorithm is applicable
      for any arbitrary object shift for full 180 degrees  rotation. 

PMID- 25967511
TI  - Strain field measurements around notches using SIFT features and meshless
      methods.
AB  - This work proposes a hybrid experimental-numerical technique with the aim to
      improve strain measurements at stress concentration regions. The novel technique
      is performed employing the computer vision scale invariant feature transform
      (SIFT) algorithm and meshless methods, here termed SIFT-meshless. The SIFT is
      applied to perform feature points matching in two images of the specimen surface
      at different stages of mechanical deformation. The output data are provided as a
      set of displacement measurements by tracking matched feature points. This
      information is then used to model displacement and strain field on the surface by
      means of a meshless formulation based on the moving least squares approximation.
      By applying the proposed SIFT-meshless method, the strain distribution around a
      semicircular notch in a plate under bending load was investigated. The
      experimental results were compared with those obtained by a digital image
      correlation technique based on a subset approach and to simulations from finite
      element analysis software. The experimental results demonstrated that the present
      method is capable of performing reliable strain measurements at distances close
      to the notch where the peak strain value is expected, even in the presence of
      high strain gradients. 

PMID- 25967512
TI  - Planar spoof plasmonic ultra-wideband filter based on low-loss and compact
      terahertz waveguide corrugated with dumbbell grooves.
AB  - Although subwavelength planar terahertz (THz) plasmonic devices can be
      implemented based on planar spoof surface plasmons (SPs), they still suffer from
      a little high propagation loss. Here the dispersion and propagation
      characteristics of the spoof plasmonic waveguide composed of double metal strips
      corrugated with dumbbell shaped grooves have been investigated. It has been found
      that much lower propagation loss and longer propagation length can be achieved
      based on the waveguide compared with the conventional spoof plasmonic waveguide
      with rectangular grooves. Moreover, the waveguide can implement a decrease in
      size of about 22%. An ultra-wideband THz plasmonic filter for planar circuits has
      been demonstrated based on the proposed waveguide. The experimental verification
      at the microwave frequency has been conducted by scaling up the geometry size of
      the filter. 

PMID- 25967513
TI  - Dual-wavelength filters based on two-dimensional photonic crystal degenerate
      modes with a ring dielectric rod inside the defect cavity.
AB  - A tunable dual-wavelength filter based on degenerate modes with a ring dielectric
      rod inside the single point defect cavity is proposed. The band structures and
      mode profiles are computed by the plane-wave expansion method. The normalized
      transmission spectra for this structure are investigated by using the two
      dimensional finite-difference time-domain method. The two orthogonal output modes
      of the filter can be regarded as the combination of the original degenerate
      cavity modes and both excited due to the introduced perturbation rod. The
      influences of the perturbation rod on the localized modes, band separations, and
      the tuning ranges are all investigated and analyzed based on the perturbation
      theory. With the ring dielectric rod being introduced into the defect, a narrower
      wavelength bandwidth and a wider wavelength tuning range can be obtained, which
      are superior to that of the filter based on a cavity with a larger radius rod.
      Besides, the perturbation rod can also be used for splitting degenerate modes for
      multiwavelength filters. The proposed filter has a simple structure and may be
      potentially applied in various integrated circuits, such as multiwavelength
      filters. 

PMID- 25967514
TI  - Numerical simulations of the ultrabroadband supercontinuum generation by dual
      wavelength pumping in photonic crystal fiber with two zero dispersion
      wavelengths.
AB  - Ultrabroadband supercontinuum has received considerable attention due to its
      numerous applications in practice. An ultrabroadband supercontinuum spanning from
      426 to 2954 nm is generated numerically in this paper. It is achieved by dual
      wavelength pumping with a specially designed silica photonic crystal fiber that
      has two widely separated zero dispersion wavelengths. Additionally, the
      wavelengths of dual-wavelength pumping are both located in the anomalous
      dispersion regime in our investigation, which differs from research ever
      reported. Detailed physical mechanisms as well as interaction between the
      injected two pulses are discussed explicitly. With the introduction of a second
      pump pulse in the infrared region, a blueshifted dispersive wave is excited,
      turning out to be advantageous to extend a supercontinuum further into
      ultraviolet. Interestingly, the infrared edges remain unchanged whether a pulse
      in near infrared is added or not. The pulse synchronization issue is studied
      thoroughly and the conclusion that the two pulses can encounter within the used
      fiber length is declared.

PMID- 25967515
TI  - Terahertz wave transmission within metal-clad antiresonant reflecting hollow
      waveguides.
AB  - We present the transmission characteristics of THz waves in metal-clad
      antiresonant reflecting hollow waveguides. We have derived the equation for the
      blueshift of the resonance frequency. The effects of the waveguide structure on
      the blueshift of the resonance frequency are studied comprehensively. In
      particular, we find that the blueshift of the resonance frequency is strongly
      affected by the interval between two dielectric slabs. By changing the interval,
      we find that the maximum frequency-tuning range is up to 2030 GHz and the maximum
      sensitivity of the resonance frequency shift is up to 6950 GHz/mm at the
      resonance order of m=1. When the THz wave is at the near-zero loss frequency,
      both the loss and the dispersion of the guide modes are very low.

PMID- 25967516
TI  - 3.15 kW direct diode-pumped near diffraction-limited all-fiber-integrated fiber
      laser.
AB  - We demonstrate a direct diode-pumped all-fiber-integrated fiber laser based on
      master oscillator power amplifier configuration at 1080 nm, producing maximum
      output power of 3.15 kW with corresponding optical to optical efficiency of
      75.1%. Further power scaling is pump-limited and theoretical analysis
      demonstrates that 4 kW output power can be further achieved without stimulated
      Raman scattering. Near diffraction-limited beam quality (M(2) ~ 1.6 in the x and
      y directions) is also achieved at the maximum output power. This compact
      prototype laser has excellent stability and reliability, which could benefit many
      practical applications, such as industrial processing.

PMID- 25967517
TI  - Image reconstruction method based on CCD calibration in frequency domain.
AB  - We demonstrate a method to reconstruct CCD images by calculating out the pixel
      response function accurately with laser interference patterns. This method is
      proven theoretically to have the ability to improve image quality greatly and
      thus may find great application in high-quality imaging fields. 

PMID- 25967518
TI  - Schlieren-based temperature measurement inside the cylinder of an optical spark
      ignition and homogeneous charge compression ignition engine.
AB  - Schlieren [Schlieren and Shadowgraphy Techniques (McGraw-Hill, 2001); Optics of
      Flames (Butterworths, 1963)] is a non-intrusive technique that can be used to
      detect density variations in a medium, and thus, under constant pressure and
      mixture concentration conditions, measure whole-field temperature distributions.
      The objective of the current work was to design a schlieren system to measure
      line-of-sight (LOS)-averaged temperature distribution with the final aim to
      determine the temperature distribution inside the cylinder of internal combustion
      (IC) engines. In a preliminary step, we assess theoretically the errors arising
      from the data reduction used to determine temperature from a schlieren
      measurement and find that the total error, random and systematic, is less than 3%
      for typical conditions encountered in the present experiments. A Z-type, curved
      mirror schlieren system was used to measure the temperature distribution from a
      hot air jet in an open air environment in order to evaluate the method. Using the
      Abel transform, the radial distribution of the temperature was reconstructed from
      the LOS measurements. There was good agreement in the peak temperature between
      the reconstructed schlieren and thermocouple measurements. Experiments were then
      conducted in a four-stroke, single-cylinder, optical spark ignition engine with a
      four-valve, pentroof-type cylinder head to measure the temperature distribution
      of the reaction zone of an iso-octane-air mixture. The engine optical windows
      were designed to produce parallel rays and allow accurate application of the
      technique. The feasibility of the method to measure temperature distributions in
      IC engines was evaluated with simulations of the deflection angle combined with
      equilibrium chemistry calculations that estimated the temperature of the reaction
      zone at the position of maximum ray deflection as recorded in a schlieren image.
      Further simulations showed that the effects of exhaust gas recirculation and air
      to-fuel ratio on the schlieren images were minimal under engine conditions
      compared to the temperature effect. At 20 crank angle degrees before top dead
      center (i.e., 20 crank angle degrees after ignition timing), the measured
      temperature of the flame front was in agreement with the simulations (730-1320 K
      depending on the shape of the flame front). Furthermore, the schlieren images
      identified the presence of hot gases ahead of the reaction zone due to diffusion
      and showed that there were no hot spots in the unburned mixture.

PMID- 25967519
TI  - Use of high dynamic range imaging for quantitative combustion diagnostics.
AB  - High dynamic range (HDR) imaging is applied to quantitative combustion
      diagnostics in coflow laminar diffusion flames as a way to improve the signal-to
      noise ratio (SNR) and measurement sensitivity. The technique relies on the
      combination of partially saturated frames into a single unsaturated image; in
      this work, the effectiveness of the HDR approach is demonstrated when applied to
      two-color ratio pyrometry. Specifically, it is shown than an increase in SNR
      results in more precise temperature measurements for both soot and thin filament
      pyrometry. Linearity and reciprocity analysis under partially saturated
      conditions were performed on three selected detectors, and the camera response
      functions, which are required for HDR image reconstruction, were determined. The
      linearity/reciprocity of the detectors allowed the use of a simplified algorithm
      that was implemented to compute the HDR images; soot and flame temperature were
      calculated from those images by employing color-ratio pyrometry. The reciprocity
      analysis revealed that pixel cross talk can be a limiting factor in a detector's
      HDR capabilities. The comparison with low dynamic range results showed the
      advantage of the HDR approach. Due to the higher SNR, the measured temperature
      exhibits a smoother distribution, and the range is extended to lower temperature
      regions, where the pyrometry technique starts to lose sensitivity due to detector
      limitations. 

PMID- 25967520
TI  - Numerical investigation of side emission from large-area vertical-cavity surface
      emitting lasers.
AB  - For large-area ion-implanted vertical-cavity surface-emitting lasers (VCSELs),
      side emission from the edges of a chip disturbs the laser emission of a VCSEL
      mode, and suppression of it is fundamental. In this paper, we present results of
      a numerical investigation of the side emission from large-area VCSELs. We have
      modeled a VCSEL structure by an infinitely broad layer structure with mirror loss
      at the edge surfaces. Estimated threshold gains indicate that laser emission
      occurs either in a VCSEL mode or in an edge-emitting Fabry-Perot (EEFP) mode.
      Calculated emitter length dependence of the threshold gain of these modes shows
      good agreement with experimental results, and the side emission is verified to be
      the laser emission of the EEFP mode. We have also discussed the way to suppress
      the side emission and confirmed that our recent achievement of over 200 W quasi
      continuous-wave output from an ion-implanted VCSEL array is due to antireflection
      coatings of the edges and introduction of optical losses in ex-emitter regions.

PMID- 25967521
TI  - Subnanometer absolute displacement measurement using a frequency comb referenced
      dual resonance tracking Fabry-Perot interferometer.
AB  - Fabry-Perot (F-P) interferometry is a traceable high-resolution method for
      displacement metrology that has no nonlinearity. Compared with the single
      resonance tracking F-P interferometry, the dual resonance tracking (DRT) F-P
      interferometer system is able to realize tens of millimeters measurement range
      while maintaining the intrinsic high resolution. A DRT F-P system is thus
      developed for absolute displacement measurement in metrology applications. Two
      external cavity diode lasers (ECDLs) are simultaneously locked to two resonances
      of a high-finesse F-P cavity using the Pound-Drever-Hall locking scheme. The
      absolute optical frequencies of the locked ECDLs are measured using a reference
      diode laser, with the frequency stabilized and controlled by an optical frequency
      comb. The absolute cavity resonance order numbers are investigated. The
      measurement range is experimentally tested to achieve 20 mm, while the resolution
      reaches ~10 pm level, mainly limited by the mechanical stability of the F-P
      cavity. Compared with the measurement results from a self-developed displacement
      angle heterodyne interferometer, the displacement residuals are within 10 nm in
      the range of 20 mm. This high-resolution interferometer may become a candidate
      for length metrology such as in Watt balance or Joule balance projects.

PMID- 25967522
TI  - Infrared hollow optical fiber probes for reflectance spectral imaging.
AB  - Systems for infrared reflectance imaging are built with an FT-IR spectrometer,
      hollow optical fibers, and a high-speed infrared camera. To obtain reflectance
      images of biological samples, an optical fiber probe equipped with a light source
      at the distal end and a hybrid fiber probe composed of fibers for beam radiation
      and ones for image detection have been developed. By using these systems,
      reflectance spectral images of lipid painted on biomedical hard tissue, which
      provides reflectance of around 4%, are successfully acquired. 

PMID- 25967523
TI  - One-way regular electromagnetic mode immune to backscattering.
AB  - In this paper, we present a basic model of robust one-way electromagnetic modes
      at microwave frequencies, which is formed by a semi-infinite gyromagnetic yttrium
      iron-garnet with dielectric cladding terminated by a metal plate. It is shown
      that this system supports not only one-way surface magnetoplasmons (SMPs) but
      also a one-way regular mode, which is guided by the mechanism of total internal
      reflection. Like one-way SMPs, the one-way regular mode can be immune to
      backscattering, and two types of one-way modes together make up a complete
      dispersion band for the system. 

PMID- 25967524
TI  - Authors' Reply to the Letter by Madias Entitled '"Bronchogenic Stress
      Cardiomyopathy", a subset of Takotsubo Syndrome'.

PMID- 25967525
TI  - Translational potential of cancer stem cells: A review of the detection of cancer
      stem cells and their roles in cancer recurrence and cancer treatment.
AB  - Cancer stem cells (CSCs) are a subpopulation of cancer cells with many clinical
      implications in most cancer types. One important clinical implication of CSCs is
      their role in cancer metastases, as reflected by their ability to initiate and
      drive micro and macro-metastases. The other important contributing factor for
      CSCs in cancer management is their function in causing treatment resistance and
      recurrence in cancer via their activation of different signalling pathways such
      as Notch, Wnt/beta-catenin, TGF-beta, Hedgehog, PI3K/Akt/mTOR and JAK/STAT
      pathways. Thus, many different therapeutic approaches are being tested for
      prevention and treatment of cancer recurrence. These may include treatment
      strategies targeting altered genetic signalling pathways by blocking specific
      cell surface molecules, altering the cancer microenvironments that nurture cancer
      stem cells, inducing differentiation of CSCs, immunotherapy based on CSCs
      associated antigens, exploiting metabolites to kill CSCs, and designing small
      interfering RNA/DNA molecules that especially target CSCs. Because of the huge
      potential of these approaches to improve cancer management, it is important to
      identify and isolate cancer stem cells for precise study and application of prior
      the research on their role in cancer. Commonly used methodologies for detection
      and isolation of CSCs include functional, image-based, molecular, cytological
      sorting and filtration approaches, the use of different surface markers and
      xenotransplantation. Overall, given their significance in cancer biology,
      refining the isolation and targeting of CSCs will play an important role in
      future management of cancer.

PMID- 25967527
TI  - Effect of a Fenestration Between an Intrascleral Lake and Supraciliary Space on
      Deep Sclerectomy.
AB  - PURPOSE: To evaluate the effects of a scleral fenestration on the surgical
      outcomes of modified deep sclerectomy (DS). METHODS: We retrospectively studied
      the surgical outcomes of 83 eyes of 83 patients after modified DS for primary
      open-angle glaucoma (POAG) or ocular hypertension. In 39 eyes, combination of DS,
      incision of the trabeculo-Descemet's membrane, and iridectomy were performed (DSF
      ); in 44 eyes, a scleral fenestration between the supraciliary space and lake was
      added to the DSF- (DSF+). Forty-eight eyes of 48 patients with POAG who underwent
      trabeculectomy with adjunctive mitomycin C (lect MMC) served as controls.
      RESULTS: The probability of bleb survival was more common in the following order:
      lect MMC>DSF->DSF+ (P=0.0029). A significantly greater intraocular pressure (IOP)
      reduction occurred in the lect MMC group compared with the DSF+ (P=0.0015) and
      DSF- (P=0.0006) groups. So far as the eyes that underwent DS were concerned, bleb
      formation (P=0.0130) and a scleral bed fenestration (P=0.0315) significantly
      lowered the IOP by the Cox proportional hazard model. In eyes treated with DSF+,
      the positive IOP-lowering effect of the fenestration was counterbalanced by
      inhibited bleb formation and resulted in equivalent IOP reductions in the DSF+
      and DSF- groups (P=0.9881). IOP reduction by DSF+ without a bleb was 25.0% at 1
      year (P=0.00015) and this reduction increased to 43.2% (P=0.0001) when eyes
      accompany a bleb and scleral fenestration. CONCLUSIONS: Both the scleral
      fenestration and bleb formation lower IOP, whereas the scleral fenestration
      suppresses bleb formation in patients treated with DS.

PMID- 25967526
TI  - Effect of Switching to Travoprost Preserved With SofZia in Glaucoma Patients With
      Chronic Superficial Punctate Keratitis While Receiving BAK-preserved Latanoprost.
AB  - PURPOSE: To assess the effect of switching 1 eye to topical travoprost 0.004%
      preserved with SofZia (TRAVATAN Z solution) in patients who had chronic
      superficial punctate keratitis (SPK) in both eyes treated with benzalkonium
      chloride-preserved latanoprost 0.005% (XALATAN). METHODS: This was a prospective,
      randomized, controlled, multicenter, open-label, comparative 3-month follow-up
      study. Patients with open-angle glaucoma or ocular hypertension who received
      XALATAN monotherapy for at least 3 months and had SPK in both eyes were enrolled
      at 9 facilities. For each patient, 1 eye was randomly selected and switched to
      TRAVATAN Z solution (T-group); the contralateral control eye was treated with
      XALATAN (X-group). SPK in 5 corneal regions, conjunctival hyperemia, tear breakup
      time (TBUT), and intraocular pressure (IOP) were examined in a masked manner at
      baseline, 1 month, and 3 months. Changes in SPK, hyperemia, TBUT, and IOP were
      compared within treatment groups and between treatment groups. RESULTS: Fifty-six
      patients completed the study. The frequency of SPK significantly decreased from
      baseline in the T-group and the X-group at 1 and 3 months (T-group, P<0.001; X
      group, P<0.05). In the T-group, SPK scores were significantly improved in 4
      corneal regions, excluding the superior region, at 1 and 3 months (all P<0.05),
      whereas in the X-group, SPK scores were significantly improved only in the
      temporal region at 1 month and in the inferior region at 3 months (P<0.05 for
      both). The total SPK score at 1 and 3 months in the T-group was significantly
      lower compared with the score in the X-group (P=0.0023 and 0.0102, respectively).
      The SPK score for the superior and central corneal region at 3 months in the T
      group was significantly lower compared with the score in the X-group (P=0.0212
      and 0.022, respectively). There were no substantial intergroup or intragroup
      differences in changes from baseline for hyperemia scores, TBUT, or IOP
      reduction. CONCLUSIONS: Switching therapy from benzalkonium chloride-preserved
      latanoprost to travoprost preserved with SofZia ameliorated chronic SPK. There
      were no clinically relevant changes in hyperemia, TBUT, or IOP.

PMID- 25967528
TI  - Adjunctive Mitomycin C or Amniotic Membrane Transplantation for Ahmed Glaucoma
      Valve Implantation: A Randomized Clinical Trial.
AB  - PURPOSE: To determine whether adjunctive mitomycin C (MMC) or amniotic membrane
      transplantation (AMT) improve the outcomes of Ahmed glaucoma valve (AGV)
      implantation. METHODS: This double-blind, stratified, 3-armed randomized clinical
      trial includes 75 eyes of 75 patients aged 7 to 75 years with refractory
      glaucoma. Eligible subjects underwent stratified block randomization; eyes were
      first stratified to surgery in the superior or inferior quadrants based on
      feasibility; in each subgroup, eyes were randomly assigned to the study arms
      using random blocks: conventional AGV implantation (group A, 25 eyes), AGV with
      MMC (group B, 25 eyes), and AGV with AMT (group C, 25 eyes). RESULTS: The 3 study
      groups were comparable regarding baseline characteristics and mean follow-up
      (P=0.288). A total of 68 patients including 23 eyes in group A, 25 eyes in group
      B, and 20 eyes group C completed the follow-up period and were analyzed.
      Intraocular pressure was lower in the MMC group only 3 weeks postoperatively
      (P=0.04) but comparable at other time intervals. Overall success rate was
      comparable in the 3 groups at 12 months (P=0.217). The number of eyes requiring
      medications (P=0.30), time to initiation of medications (P=0.13), and number of
      medications (P=0.22) were comparable. Hypertensive phase was slightly but
      insignificantly more common with standard surgery (82%) as compared with MMC
      augmented (60%) and AMT-augmented (70%) procedures (P=0.23). Complications were
      comparable over 1 year (P=0.28). CONCLUSIONS: Although adjunctive MMC and AMT
      were safe during AGV implantation, they did not influence success rates or
      intraocular pressure outcomes. Complications, including hypertensive phase, were
      also comparable.

PMID- 25967529
TI  - A Novel KERA Mutation in a Case of Autosomal Recessive Cornea Plana With Primary
      Angle-Closure Glaucoma.
AB  - PURPOSE: Keratocan is a cornea-specific keratan sulfate proteoglycan found
      predominantly in the adult vertebrate eye. In human beings, mutations in
      keratocan (KERA) are associated with autosomal recessive cornea plana (CNA2),
      which is characterized by a flattened forward convex curvature of the cornea.
      Here, we report a novel mutation in a case of autosomal recessive bilateral
      cornea plana presenting with primary angle-closure glaucoma in a 41-year-old
      woman from Eastern India. METHODS: The KERA gene of the patient and her sons was
      directly sequenced. RESULTS: Mutational analysis of the KERA revealed 2 novel
      mutations. The first mutation was a 3 base-pair deletion (c.371_373delTCT),
      leading to the loss of a highly conserved amino acid (p.Phe125del). The second
      mutation was a base substitution resulting in a silent mutation (c.69G>A). One of
      her 2 sons carried the homozygous substitution (c.69G>A), whereas the other son
      was heterozygous (c.69G>R). CONCLUSIONS: The mutation that we report here leads
      to the deletion of a conserved amino acid (p.Phe125del) from the third LRR motif
      of the keratocan protein, which might lead to an abnormal tertiary structure of
      the protein, thereby leading to the disease.

PMID- 25967530
TI  - Reversible Conjunctival Pigmentation Associated With Prostaglandin Use.
AB  - A 54-year-old Indian male with a diagnosis of ocular hypertension was started on
      a prostaglandin analog (PGA) in both eyes to lower intraocular pressure. Six
      years later, he developed progressively increasing bilateral limbal conjunctival
      hyperpigmentation. Travoprost was discontinued and replaced with brinzolamide and
      over the next year, the patient's conjunctival pigmentation improved
      significantly in both the eyes. This case report documents with slit-lamp
      photography the first case of conjunctival pigmentation associated with PGA use
      that has been shown to have reversal with discontinuation of the PGA. Because of
      the widespread use of PGAs, and the evolving nature of the conjunctival
      pigmentation, clinicians should be aware of this reversible condition when
      considering biopsy or removal of conjunctival melanocytic lesions. 

PMID- 25967531
TI  - Early functional outcome of two different orthotic concepts in ankle sprains: a
      randomized controlled trial.
AB  - INTRODUCTION: Purpose of the study was the evaluation of the early functional
      outcome of patients with an acute ankle sprain treated either with a semirigid,
      variable, phase-adapted modular ankle orthosis or an invariable orthotic
      reference device. MATERIALS AND METHODS: Forty-seven patients with acute ankle
      sprain grade II or more were included. In addition, 77 healthy controls as a
      reference were investigated. The injured subjects were treated with one of the
      two devices by random for 6 weeks. Ankle scores (FAOS, AOFAS) were taken at
      baseline after injury, 1 and 3 months after injury. Functional performance tests
      (balance platform, zig zag run, shuttle run, vertical drop jump) were performed
      at 1 and 3 months after injury. RESULTS: No significant score differences could
      be found between the two intervention groups except for achieving a preinjury
      activity level after 3 months only in the modular orthosis group. Postural
      functional performances (balance test) also showed no significant differences
      whereas the results of the agility tests revealed small but significant better
      results in the modular orthosis group in comparison to the invariable orthosis
      group. Cohen's effect sizes were high. CONCLUSION: Differences between the two
      intervention groups were marginal and very small but significant and--regarding
      Cohen's effect sizes--effective. Especially relating to functional performance,
      this might be a careful indication that a more effective strategy for promoting a
      protected, rapid recovery to physical activity after ankle sprains might be
      achieved by applying a phase-adapted ankle orthosis. Especially in athletic
      patients, phase-adapted orthosis should be further investigated and considered to
      ensure fully protected ligament healing as well as to regain early functional
      recovery.

PMID- 25967532
TI  - Image-free navigated coracoclavicular drilling for the repair of
      acromioclavicular joint dislocation: a cadaver study.
AB  - BACKGROUND: Reconstruction of the coracoclavicular ligament functions to restore
      anatomic alignment of the clavicle and may improve biomechanical function and
      clinical outcomes. Improper placement of the coracoclavicular tunnel may
      inherently weaken the coracoid. The purpose of this study was to evaluate the
      feasibility and accuracy of navigated image-free placement of K-wires for
      coracoclavicular tunnel position in comparison to conventional drill guide-based
      placement. MATERIALS AND METHODS: Eight human shoulder specimens were assigned
      for conventional technique with a coracoclavicular guide device (group CP) and
      the paired contralateral side for the navigated procedure (group NP) with an
      optoelectronic system with a fluoro-free software module. First-pass accuracy (%)
      and the K-wire trajectory (lateral-center orientation (LC), center-center (CC)
      orientation and medial-center orientation (MC) were measured. RESULTS: In all
      navigated K-wires a 100 % first-pass accuracy was observed. In three of the eight
      (37.5 %) specimens of the drill guide-based group, drilling had to be repeated.
      One of them had to be repeated twice, resulting in eight versus twelve drillings
      for the navigated versus conventional group, respectively (p = 0.021). K-wire
      trajectory showed an MC orientation in most of the specimen (n = 9, group NP 4,
      group CP 5). CONCLUSIONS: Image-free navigated coracoclavicular drilling for the
      repair of acromioclavicular joint dislocation has higher first-pass accuracy in
      comparison to conventional drill guide-based placement and, therefore, may enable
      a precise anatomic position of the drill holes and reduce the risk of an
      iatrogenic coracoid fracture.

PMID- 25967533
TI  - Wrist kinematics after radiolunate arthrodesis.
AB  - INTRODUCTION: Analysis of carpal kinematics after radiolunate and
      radioscapholunate arthrodesis shows good preservation of midcarpal joint
      congruity and motion. However, no biomechanical data exist on carpal kinematics
      after radiolunate arthrodesis in the wrist. Purpose of this study was to examine
      the individual motion of scaphoid, capitate and triquetrum after simulated
      radiolunate arthrodesis. MATERIALS AND METHODS: Radiolunate arthrodesis was
      simulated in three fresh human cadaver wrists by means of Kirschner wires.
      Individual motion of the scaphoid, triquetrum and capitate relative to the radius
      was measured for extension/flexion and radial-ulnar deviation before and after
      arthrodesis. Photostereogrammetric measurement was carried out and the helical
      axis concept of motion was employed. RESULTS: Global wrist motion, corresponding
      to capitate motion, was found to be reduced 33-50 % for extension/flexion and 25
      43 % for radial-ulnar deviation. Relative motion of the scaphoid for
      extension/flexion was found to be reduced 20 % more and for radial-ulnar
      deviation 10 % more than that of the capitate. Relative motion of the triquetrum
      for extension/flexion was found to be reduced 30 % more and for radial-ulnar
      deviation 20 % more than that of the capitate. The pattern of motion of the
      capitate hardly changed, and that of the scaphoid, only slightly. The triquetrum
      lost its rotational pattern of motion and gave way to tilting movements instead.
      The physiological function of the scaphoid between distal radius and distal
      carpal row was preserved. CONCLUSION: The presented data conform with the good
      clinical results obtained after radiolunate arthrodesis in the rheumatoid wrist
      and furthermore, encourage its use in the posttraumatic wrist.

PMID- 25967534
TI  - Update on Head and Neck Cancer: Current Knowledge on Epidemiology, Risk Factors,
      Molecular Features and Novel Therapies.
AB  - Tobacco use and alcohol consumption are the main risk factors associated with
      head and neck squamous cell carcinoma (SCC) development due to their cytotoxic
      and mutagenic effects on the exposed epithelia of the upper aerodigestive tract.
      Epstein-Barr virus (EBV) and high-risk human papillomaviruses (HPVs), both
      encoding viral oncoproteins able to interfere with cell cycle control, have been
      recognized as the etiological agents of nasopharynx carcinoma and a fraction of
      oropharyngeal carcinoma, respectively. Head and neck SCC is a deadly disease and
      despite innovative treatments represents a major challenge for patients.
      Recently, a number of genomic studies have highlighted the molecular
      heterogeneity of head and neck SCC based on methylation profiles, microRNA
      expression, mutated genes and new druggable pathways which may represent new
      targets for cancer-tailored therapies. To date, cetuximab is the only FDA
      approved anti-epidermal growth factor receptor therapy for the treatment of head
      and neck SCC. In addition, a number of monoclonal antibodies targeting AKT, mTOR
      and PI3K pathways are under evaluation. Several therapeutic vaccines against
      HPV16 and EBV proteins are also under study. The purpose of this article is to
      review the epidemiology, pathogenesis and molecular features of head and neck
      SCC, with an emphasis on new therapies.

PMID- 25967536
TI  - Different genetic factors underlie fear conditioning and episodic memory.
AB  - OBJECTIVE: Fear conditioning seems to account for the acquisition of post
      traumatic stress disorder, whereas conscious recall of events in aftermath of
      trauma reflects episodic memory. Studies show that both fear conditioning and
      episodic memory are heritable, but no study has evaluated whether they reflect
      common or separate genetic factors. To this end, we studied episodic memory and
      fear conditioning in 173 healthy twin pairs using visual stimuli predicting
      unconditioned electric shocks. METHODS: Fear conditioning acquisition and
      extinction was determined using conditioned visual stimuli predicting
      unconditioned mild electric shocks, whereas electrodermal activity served as the
      fear learning index. Episodic memory was evaluated using cued recall of pictorial
      stimuli unrelated to conditioning. We used multivariate structural equation
      modeling to jointly analyze memory performance and acquisition as well as
      extinction of fear conditioning. RESULTS: Best-fit twin models estimated moderate
      genetic loadings for conditioning and memory measures, with no genetic
      covariation between them. CONCLUSION: Individual differences in fear conditioning
      and episodic memory reflect distinct genetically influenced processes, suggesting
      that the genetic risk for learning-induced anxiety disorders includes at least
      two memory-related genetic factors. These findings are consistent with the facts
      that the two separate learning forms are distant in their evolutionary
      development, involve different brain mechanisms, and support that genetically
      independent memory systems are pivotal in the development and maintenance of
      syndromes related to fear learning.

PMID- 25967535
TI  - Identification and functional characterization of Toll-like receptor 2-1 in
      geese.
AB  - BACKGROUND: Toll-like receptor 2 (TLR2), an important pattern recognition
      receptor, activates proinflammatory pathways in response to various pathogens. It
      has been reported in humans and chicken, but not in geese, an important waterfowl
      species in China. Since some vaccines stimulate robust immune responsesl in
      chicken but not in geeeses we speculated that their immune systems are different.
      RESULTS: In this study, we cloned the goose TLR2-1 gene using rapid amplification
      of cDNA ends (RACE)and showed that geese TLR2-1 encoded a 793-amino-acid protein,
      containing a signal secretion peptide, an extracellular leucine-rich repeat
      domain, a transmembrane domain and a Toll/interleukin-1 receptor signaling domain
      deduced from amino acid sequence. TLR2-1 shared 38.4%-93.5% homology with its
      homologues in other species. Tissue expression of geese TLR2-1 varied markedly,
      and was higher in kidney, cloacal bursa, skin and brain compared to other
      organs/tissues. HEK293 cells transfected with plasmids carrying goose TLR2-1 and
      NF-kappaB-luciferase responded significantly to stimulation with Mycoplasma
      fermentans lipopeptide. Furthermore, geese infected with Mycoplasma gallisepticum
      (MG) and Salmonella enteritidis (SE) showed significant upregulation of TLR2-1 in
      both in vivo and in vitro. CONCLUSION: Geese TLR2-1 is a functional homologue of
      TLR2 present in other species and plays an important role in bacterial
      recognition in geese.

PMID- 25967537
TI  - Effects of genetic variations in NRG1 on cognitive domains in patients with
      schizophrenia and healthy individuals.
AB  - BACKGROUND: The neuregulin 1 (NRG1) gene has been investigated as a candidate
      susceptibility gene for schizophrenia. A number of studies have also explored the
      genetic effect of NRG1 on cognitive deficits related to schizophrenia, and thus
      far generated inconsistent results. The current study aimed to determine whether
      genetic variations in NRG1 are associated with cognitive domains in schizophrenic
      patients and healthy individuals. MATERIALS AND METHODS: Comprehensive
      neuropsychological tests composed of six cognitive domains were administered to
      135 clinically stable patients with schizophrenia and 119 healthy individuals. On
      the basis of previous reports of positive association, a total of four single
      nucleotide polymorphisms were analyzed. In testing the genotype effect on
      cognitive domains, we used repeated-measure analysis for six cognitive domain
      scores of each individual as repeated measurements. RESULTS: An association of P
      value less than 0.05 with at least one cognitive domain in patients and/or
      healthy individuals was observed for all of the single nucleotide polymorphisms.
      After applying the correction for multiple testing, the association remained
      statistically significant between rs6994992 and general cognitive ability (g) in
      the patient group and between rs2439272 and the 'working memory' domain in the
      group of healthy participants. CONCLUSION: This study suggests the involvement of
      NRG1 in the susceptibility for developing cognitive deficits in schizophrenic
      patients. For some cognitive domains, its genetic effect was also significant in
      generating interindividual variability within the normal functional range.

PMID- 25967538
TI  - Cytochrome P450 2D6 genotype affects the pharmacokinetics of controlled-release
      paroxetine in healthy Chinese subjects: comparison of traditional phenotype and
      activity score systems.
AB  - PURPOSE: This study evaluated the effects of cytochrome P450 (CYP) 2D6
      polymorphisms on the pharmacokinetics of controlled-release paroxetine in healthy
      Chinese subjects and used paroxetine as a tool drug to compare the performance of
      traditional phenotype and activity score systems. METHODS: Pharmacokinetic data
      were evaluated in 24 subjects who received a single oral dose of 25 mg controlled
      release paroxetine. Plasma paroxetine concentrations were measured by LC-MS/MS.
      CYP2D6 genotypes were tested by PCR and direct DNA sequencing. Subjects were
      classified by two systems of phenotype prediction. In the traditional phenotype
      system, subjects were classified as extensive metabolizers or intermediate
      metabolizers; in the activity score system, subjects were divided into four
      activity groups. Analysis of variance testing was applied to estimate the effects
      of CYP2D6 polymorphisms on the pharmacokinetics of paroxetine. RESULTS: With the
      traditional phenotype system, significant differences were observed in the
      following pharmacokinetic parameters of paroxetine: t 1/2, C max, AUC0-t, AUC0
      inf, Vz/F, and CL/F (all P < 0.05). The AUC or exposure of paroxetine was about
      3.5-fold higher in the intermediate metabolizer group than in the extensive
      metabolizer group. With the activity score system, significant differences were
      observed in the t 1/2, C max, AUC0-t, AUC0-inf, Vz/F, and CL/F among the four
      different activity score groups (all P < 0.05). We found that the AUC of
      paroxetine decreased by around one half as the activity score increased by 0.5.
      CONCLUSION: The pharmacokinetics of controlled-release paroxetine after a single
      administration was affected by CYP2D6 polymorphisms. Both the traditional
      phenotype and the activity score systems performed well and distinguished
      subjects with different drug exposures. The activity score system provided a more
      detailed classification for the subjects.

PMID- 25967541
TI  - Dysexecutive functioning in ALS patients and its clinical implications.
AB  - Pronounced cognitive and behavioural impairments in amyotrophic lateral sclerosis
      (ALS) concern executive functions and executive behaviour. The valid measurement
      is challenging as motor disabilities may mask everyday functioning. The aim of
      this study was to determine a detailed characteristic pattern of executive
      impairment in ALS in order to effectively interpret their clinical impact. We
      investigated 98 ALS patients without or with frontotemporal dementia (FTD), and
      70 healthy controls using a comprehensive neuropsychological test battery
      focusing on executive functions and executive behaviour. We analysed the
      impairment of executive functions and their clinical significance for patients'
      daily routines. Results demonstrated that around 70% of cognitively impaired ALS
      patients without FTD showed disturbances in executive functioning. Behavioural
      abnormalities primarily manifested in symptoms of apathy. Patients without FTD
      were most impaired in the executive domain regarding initiation and shifting;
      this contrasted their almost preserved processes relating to updating,
      inhibition, and complex problem solving. ALS-FTD patients showed deficits in all
      analysed processes. Our study suggests that executive dysfunctioning in
      cognitively impaired ALS patients without FTD does not preferentially affect the
      more complex regulatory processes. These findings indicate potential mechanisms
      for ALS patients to compensate for executive dysfunction in daily routine. 

PMID- 25967539
TI  - Prescription pain medications and chronic headache in Denmark: implications for
      preventing medication overuse.
AB  - PURPOSE: The aim of the present paper is to study which prescription pain
      medications are most commonly dispensed to people with chronic headache (CH),
      particularly those with medication-overuse headache (MOH). METHODS: This cross
      sectional study analysed prescription pain medications dispensed within 1 year to
      68,518 respondents of a national health survey. Participants with headache >= 15
      days per month for 3 months were classified as having CH. Those with CH and over
      the-counter analgesic use >= 15 days per month or purchase of >= 20 or >= 30
      defined daily doses (DDDs) of prescription pain medication per month (depending
      on the drug) were classified as having MOH. Associations between CH and other
      chronic pain conditions were analysed by logistic regression. RESULTS: Among
      those with CH (adjusted prevalence 3.3%, CI 3.2-3.5%), pain medications most
      commonly dispensed were paracetamol, tramadol, ibuprofen and codeine. CH was
      associated with osteoarthritis, back pain, and rheumatoid arthritis. Among those
      with MOH, 32.4% were dispensed an opioid at least once within 1 year. Only 5.1%
      of people with CH were dispensed triptans. CONCLUSIONS: High prevalence of opioid
      use among people with CH may be due to inappropriate headache treatment or
      development of MOH among those treated for other pain conditions. While there
      were cases of triptan overuse, triptans remain underutilized among those with CH,
      suggesting that migraine may be under-recognized and inappropriately treated,
      leading to overuse of other medications. Education of physicians on appropriate
      headache management is essential for MOH prevention. There is a need to increase
      universal awareness about MOH as an adverse effect of long-term analgesic use.

PMID- 25967542
TI  - Validation of the Edinburgh Cognitive and Behavioural Amyotrophic Lateral
      Sclerosis Screen (ECAS): A cognitive tool for motor disorders.
AB  - Our objective was to assess the validity of the Edinburgh Cognitive and Behaviour
      ALS Screen (ECAS), a multi-domain screen designed to detect cognitive deficits in
      patients with motor disorders. Forty ALS patients (without pre-diagnosed
      dementia) and 40, age-, gender- and education-matched healthy controls were
      recruited. All participants underwent extensive neuropsychological assessment and
      the ECAS. Performance at neuropsychological assessment across five domains
      (fluency, executive function, language, memory and visuospatial function) was
      compared to the ECAS ALS-Specific (fluency, executive functions and social
      cognition, language), ALS Non-specific (memory, visuospatial functions), and
      Total scores. Data from the healthy controls produced population-based
      abnormality cut-offs: composite score performance <= 2 SD in any domain
      classified impairment at neuropsychological assessment. Thirty-three percent of
      patients were impaired, most commonly in a single domain (executive or language
      dysfunction). Receiver Operator Curve (ROC) analyses using ECAS Total scores and
      ALS-Specific scores revealed 85% sensitivity and 85% specificity in the detection
      of cognitive impairment characteristic of ALS (fluency, executive function,
      language). A five-point borderline range produced optimal values (ALS-Specific
      Score 77-82, and ECAS-Total Score 105-110). In conclusion, validation against
      gold standard extensive neuropsychology demonstrated that the ECAS is a screening
      tool with high sensitivity and specificity to impairment characteristic of ALS. 

PMID- 25967540
TI  - The EU(7)-PIM list: a list of potentially inappropriate medications for older
      people consented by experts from seven European countries.
AB  - PURPOSE: The aim of the study was to develop a European list of potentially
      inappropriate medications (PIM) for older people, which can be used for the
      analysis and comparison of prescribing patterns across European countries and for
      clinical practice. METHODS: A preliminary PIM list was developed, based on the
      German PRISCUS list of potentially inappropriate medications and other PIM lists
      from the USA, Canada and France. Thirty experts on geriatric prescribing from
      Estonia, Finland, France, the Netherlands, Spain and Sweden participated; eight
      experts performed a structured expansion of the list, suggesting further
      medications; twenty-seven experts participated in a two-round Delphi survey
      assessing the appropriateness of drugs and suggesting dose adjustments and
      therapeutic alternatives. Finally, twelve experts completed a brief final survey
      to decide upon issues requiring further consensus. RESULTS: Experts reached a
      consensus that 282 chemical substances or drug classes from 34 therapeutic groups
      are PIM for older people; some PIM are restricted to a certain dose or duration
      of use. The PIM list contains suggestions for dose adjustments and therapeutic
      alternatives. CONCLUSIONS: The European Union (EU)(7)-PIM list is a screening
      tool, developed with participation of experts from seven European countries, that
      allows identification and comparison of PIM prescribing patterns for older people
      across European countries. It can also be used as a guide in clinical practice,
      although it does not substitute the decision-making process of individualised
      prescribing for older people. Further research is needed to investigate the
      feasibility and applicability and, finally, the clinical benefits of the newly
      developed list.

PMID- 25967543
TI  - Distal bimelic amyotrophy (DBMA): Phenotypically distinct but identical on
      cervical spine MR imaging with brachial monomelic amyotrophy/Hirayama disease.
AB  - Our objective was to characterize the MR imaging features in a large and distinct
      series of distal bimelic amyotrophy (DBMA) from India. We utilized a
      retrospective and prospective study on 26 cases. Results demonstrated that upper
      limb distal muscle wasting and weakness was predominantly symmetrical in onset.
      Mean age at onset was 20.9 +/- 7.0 years, mean duration 83.0 +/- 102.6 months.
      MRI carried out in 22 patients with flexion studies showed forward displacement
      of posterior dura in 19 (86.4%). Crescent shaped epidural enhancement on contrast
      was seen in 20/24 cases (83.3%), and bilateral T2W hyperintensities of cord in17
      (65.4%) - symmetrical in15 cases. Maximum hyperintensity was noted at C5-C6, C6
      C7 levels. Cord atrophy was noted in 24 (92.3%) cases (most affected: C5-C6, C6
      C7) - symmetrical atrophy in 21cases. Cervical spine straightening occurred in
      six (23.1%) cases and reversal of lordosis in 15 (57.7%). In conclusion, this
      study confirms that DBMA is phenotypically distinct but pathophysiologically the
      same as brachial monomelic amyotrophy (BMMA) on MR imaging. Typical MRI features
      were seen in all. It is important to differentiate this disorder from ALS, which
      could present at a younger age as often seen among Indians. The clinical and MR
      imaging features are highly suggestive that DBMA, as with BMMA/Hirayama disease,
      occurs due to dynamic alterations at the cervical spine level. 

PMID- 25967544
TI  - Extrapyramidal and cognitive signs in amyotrophic lateral sclerosis: A population
      based cross-sectional study.
AB  - Our objective was to assess the association between amyotrophic lateral sclerosis
      (ALS) and other neurodegenerative diseases such as Alzheimer's disease (AD),
      frontotemporal dementia (FTD) and Parkinson's disease (PD). From May 2007 through
      August 2012 we investigated 146 patients with newly diagnosed ALS and 146 age-
      and gender-matched controls. Each individual was screened for cardinal
      extrapyramidal signs (neurological examination) and cognitive dysfunction (Mini
      Mental State Examination, MMSE and Frontal Assessment Battery, FAB). Results
      demonstrated that rigidity was present in 8.2% of cases and 2.1% of controls
      (adjusted odds ratio, adjOR 5.7; 95% CI 1.5-22.0). The corresponding percentages
      for bradykinesia and postural instability were, respectively, 8.2 vs. 2.7% (adjOR
      4.8; 95% CI 1.4-16.5) and 2.7 vs. 9.6% (adjOR 0.3; 95% CI 0.1-0.9). FAB <= 13.4
      was recorded in 24.8 vs. 9.6%; adjOR 2.9; 95% CI 1.5-5.7). Tremor and abnormal
      FAB score were predicted by an older age at onset while an abnormal FAB score was
      associated with cramps and family history of neurodegenerative diseases. In
      conclusion, our data support the notion that newly diagnosed ALS carries a higher
      than expected risk of extrapyramidal signs and FTD. 

PMID- 25967545
TI  - Bilateral motor and premotor cortex hypometabolism in a case of Mills syndrome.
AB  - Mills syndrome is a rare condition characterized by slowly progressive upper
      motor neuron-predominant hemiparesis, belonging to the motor neuron disorder
      spectrum. Predominantly unilateral primary degeneration of corticospinal pathways
      is the supposed underlying pathophysiological mechanism. By means of (18)F
      Fluorodeoxyglucose Positron Emission Tomography, we found significant
      (Statistical Parametric Mapping, SPM, analysis versus controls, uncorrected p <
      0.005 at voxel level, p < 0.05 at cluster level, corrected for multiple
      comparisons) hypometabolism in motor and premotor areas of both hemispheres,
      mainly contralateral to the limbs weakness in a patient with a 10-year history of
      slowly progressive left-sided hemiparesis. No significant grey matter loss was
      found on voxel based morphometry (SPM). This supports the hypothesis of a slowly
      progressive neurodegenerative process involving primary motor and premotor
      cortex. 

PMID- 25967546
TI  - Highly stereoselective synthesis of natural-product-like hybrids by an
      organocatalytic/multicomponent reaction sequence.
AB  - In an endeavor to provide an efficient route to natural product hybrids,
      described herein is an efficient, highly stereoselective, one-pot process
      comprising an organocatalytic conjugate addition of 1,3-dicarbonyls to alpha,beta
      unsaturated aldehydes followed by an intramolecular isocyanide-based
      multicomponent reaction. This approach enables the rapid assembly of complex
      natural product hybrids including up to four different molecular fragments, such
      as hydroquinolinone, chromene, piperidine, peptide, lipid, and glycoside
      moieties. The strategy combines the stereocontrol of organocatalysis with the
      diversity-generating character of multicomponent reactions, thus leading to
      structurally unique peptidomimetics integrating heterocyclic, lipidic, and sugar
      moieties. 

PMID- 25967548
TI  - Comment on the paper by Grunert et al. entitled 'Remarks upon the term
      stereotaxy: a linguistic and historical note'.

PMID- 25967547
TI  - Mitochondrially targeted vitamin E succinate efficiently kills breast tumour
      initiating cells in a complex II-dependent manner.
AB  - BACKGROUND: Accumulating evidence suggests that breast cancer involves tumour
      initiating cells (TICs), which play a role in initiation, metastasis, therapeutic
      resistance and relapse of the disease. Emerging drugs that target TICs are
      becoming a focus of contemporary research. Mitocans, a group of compounds that
      induce apoptosis of cancer cells by destabilising their mitochondria, are showing
      their potential in killing TICs. In this project, we investigated mitochondrially
      targeted vitamin E succinate (MitoVES), a recently developed mitocan, for its in
      vitro and in vivo efficacy against TICs. METHODS: The mammosphere model of breast
      TICs was established by culturing murine NeuTL and human MCF7 cells as spheres.
      This model was verified by stem cell marker expression, tumour initiation
      capacity and chemotherapeutic resistance. Cell susceptibility to MitoVES was
      assessed and the cell death pathway investigated. In vivo efficacy was studied by
      grafting NeuTL TICs to form syngeneic tumours. RESULTS: Mammospheres derived from
      NeuTL and MCF7 breast cancer cells were enriched in the level of stemness, and
      the sphere cells featured altered mitochondrial function. Sphere cultures were
      resistant to several established anti-cancer agents while they were susceptible
      to MitoVES. Killing of mammospheres was suppressed when the mitochondrial complex
      II, the molecular target of MitoVES, was knocked down. Importantly, MitoVES
      inhibited progression of syngeneic HER2(high) tumours derived from breast TICs by
      inducing apoptosis in tumour cells. CONCLUSIONS: These results demonstrate that
      using mammospheres, a plausible model for studying TICs, drugs that target
      mitochondria efficiently kill breast tumour-initiating cells.

PMID- 25967549
TI  - GABAB receptor promotes its own surface expression by recruiting a Rap1-dependent
      signaling cascade.
AB  - G-protein-coupled receptors (GPCRs) are key players in cell signaling, and their
      cell surface expression is tightly regulated. For many GPCRs such as beta2-AR
      (beta2-adrenergic receptor), receptor activation leads to downregulation of
      receptor surface expression, a phenomenon that has been extensively
      characterized. By contrast, some other GPCRs, such as GABA(B) receptor, remain
      relatively stable at the cell surface even after prolonged agonist treatment;
      however, the underlying mechanisms are unclear. Here, we identify the small
      GTPase Rap1 as a key regulator for promoting GABA(B) receptor surface expression.
      Agonist stimulation of GABA(B) receptor signals through Galphai/o to inhibit
      Rap1GAPII (also known as Rap1GAP1b, an isoform of Rap1GAP1), thereby activating
      Rap1 (which has two isoforms, Rap1a and Rap1b) in cultured cerebellar granule
      neurons (CGNs). The active form of Rap1 is then recruited to GABA(B) receptor
      through physical interactions in CGNs. This Rap1-dependent signaling cascade
      promotes GABA(B) receptor surface expression by stimulating receptor recycling.
      Our results uncover a new mechanism regulating GPCR surface expression and also
      provide a potential explanation for the slow, long-lasting inhibitory action of
      GABA neurotransmitter.

PMID- 25967550
TI  - alpha-synuclein and synapsin III cooperatively regulate synaptic function in
      dopamine neurons.
AB  - The main neuropathological features of Parkinson's disease are dopaminergic
      nigrostriatal neuron degeneration, and intraneuronal and intraneuritic
      proteinaceous inclusions named Lewy bodies and Lewy neurites, respectively, which
      mainly contain alpha-synuclein (alpha-syn, also known as SNCA). The neuronal
      phosphoprotein synapsin III (also known as SYN3), is a pivotal regulator of
      dopamine neuron synaptic function. Here, we show that alpha-syn interacts with
      and modulates synapsin III. The absence of alpha-syn causes a selective increase
      and redistribution of synapsin III, and changes the organization of synaptic
      vesicle pools in dopamine neurons. In alpha-syn-null mice, the alterations of
      synapsin III induce an increased locomotor response to the stimulation of
      synapsin-dependent dopamine overflow, despite this, these mice show decreased
      basal and depolarization-dependent striatal dopamine release. Of note, synapsin
      III seems to be involved in alpha-syn aggregation, which also coaxes its increase
      and redistribution. Furthermore, synapsin III accumulates in the caudate and
      putamen of individuals with Parkinson's disease. These findings support a
      reciprocal modulatory interaction of alpha-syn and synapsin III in the regulation
      of dopamine neuron synaptic function. 

PMID- 25967551
TI  - Sonic hedgehog processing and release are regulated by glypican heparan sulfate
      proteoglycans.
AB  - All Hedgehog morphogens are released from producing cells, despite being
      synthesized as N- and C-terminally lipidated molecules, a modification that
      firmly tethers them to the cell membrane. We have previously shown that
      proteolytic removal of both lipidated peptides, called shedding, releases
      bioactive Sonic hedgehog (Shh) morphogens from the surface of transfected Bosc23
      cells. Using in vivo knockdown together with in vitro cell culture studies, we
      now show that glypican heparan sulfate proteoglycans regulate this process,
      through their heparan sulfate chains, in a cell autonomous manner. Heparan
      sulfate specifically modifies Shh processing at the cell surface, and purified
      glycosaminoglycans enhance the proteolytic removal of N- and C-terminal Shh
      peptides under cell-free conditions. The most likely explanation for these
      observations is direct Shh processing in the extracellular compartment,
      suggesting that heparan sulfate acts as a scaffold or activator for Shh ligands
      and the factors required for their turnover. We also show that purified heparan
      sulfate isolated from specific cell types and tissues mediates the release of
      bioactive Shh from pancreatic cancer cells, revealing a previously unknown
      regulatory role for these versatile molecules in a pathological context. 

PMID- 25967552
TI  - The MAL protein is crucial for proper membrane condensation at the ciliary base,
      which is required for primary cilium elongation.
AB  - The base of the primary cilium contains a zone of condensed membranes whose
      importance is not known. Here, we have studied the involvement of MAL, a
      tetraspanning protein that exclusively partitions into condensed membrane
      fractions, in the condensation of membranes at the ciliary base and investigated
      the importance of these membranes in primary cilium formation. We show that MAL
      accumulates at the ciliary base of epithelial MDCK cells. Knockdown of MAL
      expression resulted in a drastic reduction in the condensation of membranes at
      the ciliary base, the percentage of ciliated cells and the length of the cilia,
      but did not affect the docking of the centrosome to the plasma membrane or
      produce missorting of proteins to the pericentriolar zone or to the membrane of
      the remaining cilia. Rab8 (for which there are two isoforms, Rab8A and Rab8b),
      IFT88 and IFT20, which are important components of the machinery of ciliary
      growth, were recruited normally to the ciliary base of MAL-knockdown cells but
      were unable to elongate the primary cilium correctly. MAL, therefore, is crucial
      for the proper condensation of membranes at the ciliary base, which is required
      for efficient primary cilium extension. 

PMID- 25967553
TI  - Hollow-organ perforation following thoracolumbar spinal injuries of fall from
      height.
AB  - INTRODUCTION: Spinal trauma is the cause of high mortality and morbidity, the
      fall from height as mechanism that can cause a wide variety of lesions,
      associated both with the direct impact on the ground and with the deceleration.
      In such fall cases greater heights and higher mortality are involved.
      PRESENTATION OF CASE: We report the successful management of life-threatening
      hollow-organ perforation following thoracolumbar spinal injury. DISCUSSION:
      Perforation of the hollow-organ in the setting of thoracolumbar trauma may delay
      the diagnosis and can have devastating consequences. CONCLUSIONS: This case
      supports the recommendation for neurosurgeon in the setting of thoracolumbar
      injury that perforation of the hollow-organ can have devastating consequences. It
      is vital to achieve an early diagnosis to improve survival rate.

PMID- 25967554
TI  - Small bowel perforation due to a migrated esophageal stent: Report of a rare case
      and review of the literature.
AB  - INTRODUCTION: Endoscopic esophageal stent placement is used to treat benign
      strictures, esophageal perforations, fistulas and for palliative therapy of
      esophageal cancer. Although stent placement is safe and effective method,
      complications are increasing the morbidity and mortality rate. We aimed to
      present a patient with small bowel perforation as a consequence of migrated
      esophageal stent. PRESENTATION OF CASE: A 77-years-old woman was admitted with
      complaints of abdominal pain, abdominal distension, and vomiting for two days.
      Her past medical history included a pancreaticoduodenectomy for pancreatic tumor
      11 years ago, a partial esophagectomy for distal esophageal cancer 6 months ago
      and an esophageal stent placement for esophageal anastomotic stricture 2 months
      ago. On abdominal examination, there was generalized tenderness with rebound.
      Computed tomography showed the stent had migrated. Laparotomy revealed a
      perforation localized in the ileum due to the migrated esophageal stent. About
      5cm perforated part of gut resected and anastomosis was done. The patient was
      exitus fifty-five days after operation due to sepsis. DISCUSSION: Small bowel
      perforation is a rare but serious complication of esophageal stent migration.
      Resection of the esophagogastric junction facilitates the migration of the stent.
      The lumen of stent is often allow to the passage in the gut, so it is troublesome
      to find out the dislocation in an early period to avoid undesired results. In our
      case, resection of the esophagogastric junction was facilitated the migration of
      the stent and late onset of the symptoms delayed the diagnosis. CONCLUSION:
      Patients with esophageal stent have to follow up frequently to preclude delayed
      complications. Additional technical procedures are needed for the prevention of
      stent migration.

PMID- 25967555
TI  - Progress toward forecasting product quality and quantity of mammalian cell
      culture processes by performance-based modeling.
AB  - The production of biopharmaceuticals requires highly sophisticated, complex cell
      based processes. Once a process has been developed, acceptable ranges for various
      control parameters are typically defined based on process characterization
      studies often comprising several dozens of small scale bioreactor cultivations. A
      lot of data is generated during these studies and usually only the information
      needed to define acceptable ranges is processed in more detail. Making use of the
      wealth of information contained in such data sets, we present here a methodology
      that uses performance data (such as metabolite profiles) to forecast the product
      quality and quantity of mammalian cell culture processes based on a toolbox of
      advanced statistical methods. With this performance based modeling (PBM) the
      final product concentration and 12 quality attributes (QAs) for two different
      biopharmaceutical products were predicted in daily intervals throughout the main
      stage process. The best forecast was achieved for product concentration in a very
      early phase of the process. Furthermore, some glycan isoforms were predicted with
      good accuracy several days before the bioreactor was harvested. Overall, PBM
      clearly demonstrated its capability of early process endpoint prediction by only
      using commonly available data, even though it was not possible to predict all QAs
      with the desired accuracy. Knowing the product quality prior to the harvest
      allows the manufacturer to take counter measures in case the forecasted quality
      or quantity deviates from what is expected. This would be a big step towards real
      time release, an important element of the FDA's PAT initiative.

PMID- 25967557
TI  - Erratum to: Effect of augmentation techniques on the failure of pedicle screws
      under cranio-caudal cyclic loading.

PMID- 25967556
TI  - Identification of a novel mutation of the COL2A1 gene in a Chinese family with
      spondyloepiphyseal dysplasia congenita.
AB  - PURPOSE: To identify potential disease-causing mutation in the COL2A1 gene in a
      Chinese family with autosomal dominant spondyloepiphyseal dysplasia congenita
      (SEDC) and to analyze the phenotype-genotype correlation. METHODS: Complete
      physical and radiographic examinations of four affected individuals from SEDC
      family were conducted. Genomic DNA were isolated from peripheral blood
      leukocytes. All 54 exons and exon-intron boundaries of the COL2A1 gene were
      amplified by polymerase chain reaction (PCR) and bidirectionally sequenced.
      RESULTS: All four affected individuals were found carried a novel missense
      mutation of c.2224G>A (p.Gly687Ser) in COL2A1, while normal members of the family
      and 50 healthy controls did not have this mutation. Protein prediction of
      missense mutation by polyphen-2 and SIFT software and mutation taster indicated
      severe damage to the function. CONCLUSIONS: c.2224G>A (p.Gly687Ser) is a novel
      mutation of COL2A1 associated with spondyloepiphyseal dysplasia congenital. There
      are heterozygous of phenotype for the mutation in members of the pedigree
      analyzed. Onset becomes more earlier and severe with each successive generation.

PMID- 25967558
TI  - Delphi method: oracle or sound judgment?

PMID- 25967559
TI  - Does intraoperative navigation improve the accuracy of pedicle screw placement in
      the apical region of dystrophic scoliosis secondary to neurofibromatosis type I:
      comparison between O-arm navigation and free-hand technique.
AB  - PURPOSE: To assess the accuracy of O-arm-navigation-based pedicle screw insertion
      in dystrophic scoliosis secondary to NF-1 and compare it with free-hand pedicle
      screw insertion technique. METHODS: 32 patients with dystrophic NF-1-associated
      scoliosis were divided into two groups. A total of 92 pedicle screws were
      implanted in apical region (two vertebrae above and below the apex each) in 13
      patients using O-arm-based navigation (O-arm group), and 121 screws were
      implanted in 19 patients using free-hand technique (free-hand group). The
      postoperative CT images were reviewed and analyzed for pedicle violation. The
      screw penetration was divided into four grades: grade 0 (ideal placement), grade
      1 (penetration <2 mm), grade 2 (penetration between 2 and 4 mm), and grade 3
      (penetration >4 mm). RESULTS: The accuracy rate of pedicle screw placement (grade
      0, 1) was significantly higher in the O-arm group (79 %, 73/92) compared to 67 %
      (81/121) of the free-hand group (P = 0.045). Meanwhile, a significantly lower
      prevalence of grade 2-3 perforation was observed in the O-arm group (21 vs. 33 %,
      P < 0.05), and the incidence of medial perforation was significantly minimized by
      using O-arm navigation compared to free-hand technique (2 vs. 15 %, P < 0.01).
      Moreover, the implant density in apical region was significantly elevated by
      using O-arm navigation (58 vs. 42 %, P < 0.001). CONCLUSION: We reported 79 %
      accuracy of O-arm-based pedicle screw placement in dystrophic NF-1-associated
      scoliosis. O-arm navigation system does facilitate pedicle screw insertion in
      dystrophic NF-1-associated scoliosis, demonstrating superiorities in the safety
      and accuracy of pedicle screw placement in comparison with free-hand technique.

PMID- 25967560
TI  - Cross-sectional area of human trunk paraspinal muscles before and after posterior
      lumbar surgery using magnetic resonance imaging.
AB  - PURPOSE: Iatrogenic injuries to paraspinal muscles during the posterior lumbar
      surgery (PLS) cause a reduction in their cross-sectional areas (CSAs) and
      contractile densities over time post-surgery. This study aims to quantify such
      alterations. METHOD: Pre- and postoperative CSAs (~6 months interval) of all
      paraspinal muscles were measured in six patients undergoing PLS using a 3-T
      magnetic resonance (MR) scanner to quantify the alterations in geometrical and
      tissue effective contractile (non-fatty) CSAs of these muscles at all lumbar
      levels. To examine the presence of any confounding effects on recorded changes
      within ~7-month period, measurements were also carried out on ten healthy
      volunteers. RESULTS: In the healthy population, an important (~22%) portion of
      CSA of the erector spinae (ES) was noncontractile at the lower lumbar levels.
      Negligible variations over time in both the total geometrical (<1.7% in average)
      and contractile (<1.2%) CSAs of muscles were observed in the healthy group (i.e.,
      no confounding effect). Following PLS, significant reductions were observed in
      the geometrical CSA of only multifidus (MF) muscle by ~14 and 11% as well as in
      its contractile CSA by ~26 and 14% at the L5-S1 and L4-L5 levels, respectively.
      CONCLUSION: The total CSA of ES at lower lumbar levels shows substantial
      noncontractile contents in both healthy and patient populations. Biomechanical
      models of the spine should hence account for the noncontractile contents using
      only the effective contractile muscle CSAs. Postoperative variations in CSAs of
      paraspinal muscles may have profound effects on patterns of muscle activities,
      spinal loading, and stability.

PMID- 25967561
TI  - Letter to the Editor concerning "High-heeled-related alterations in the static
      sagittal profile of the spino-pelvic structure in young women" by Min Dai et al.
      [Eur Spine J (2015); DOI 10.1007/s00586-015-3857-6].

PMID- 25967562
TI  - Letter to the Editor concerning "Circumferential fusion using a custom-made screw
      in the management of high-grade spondylolisthesis" (by Jouve J-L et al. [2014]
      Eur Spine J; 23:S457-S462).

PMID- 25967563
TI  - Answer to the Letter to the Editor of Brent S. Russel concerning ''High-heeled
      related alterations in the static sagittal profile of the spino-pelvic structure
      in young women'' by M. Dai, X. Li, X. Zhou, Y. Hu, Q. Luo, S. Zhou [Eur Spine J
      (2015); DOI 10.1007/s00586-015-3857-6].

PMID- 25967564
TI  - Pemetrexed in second line of non-small cell lung cancer.
AB  - Non small cell lung cancer (NSCLC), which is the leading cause of cancer
      mortality, is accounts for 85% of all cases of lung cancer. The majority of NSCLC
      patients present with advanced, unresectable disease. In advanced disease,
      chemotherapy with platinun (cisplatin or carbo-platin) in combination with a
      third-generation cytotoxic drug (gemcitabine, vinorelbine, paclitaxel or
      docetaxel) can provide a modest improvement in survival with quality of life.
      Response rates of 20%-40% can be expected with a median survival of 8-10 months
      and a 1 year survival rate of 30% - 40%. Pemetrexed, a multitargeted antifolate
      agent, has shown clear activity in mesothelioma and NSCLC. In a phase III trial,
      second line treatment with pemetrexed demonstrated overall survival comparable to
      docetaxel with a more manageable toxicity profile. Single agent pemetrexed have
      shown well tolerate in elderly patients, in combination with radiotherapy where
      we can use full dose pemetrexed. In second line, in nonsquamous NSCLC pemetrexed
      administrated with folic acid and vitamin B12, has a significant superior
      survival compared with docetaxel (9.3 vs 8.0months). Rev Port Pneumol 2008; XIV
      (Sup.2): S21-S26. 

PMID- 25967565
TI  - Lung cancer treatment - Biology based decision, from gene to histology.
AB  - Lung cancer is the main cause of cancer mortality in the whole world. Until now,
      scientific and technologic developments didn't reduce significantly the mortality
      rate. The research of new therapeutical strategies based on individual
      characteristics has constituted one of the main goals of the last years.
      Difficulties in the samples collection, execution in useful time and
      standardization of the involved technologies have been the main obstacles. The
      target therapies and the customization of chemotherapy for individual patient are
      two of the fields that potentially will be able, in short-term, to determine
      important benefits for lung cancer patients. Rev Port Pneumol 2008; XIV (Sup.2):
      S27-S34. 

PMID- 25967566
TI  - Mesothelioma treatment.
AB  - Malignant mesothelioma (MM) is a locally aggressive advanced tumour, with bad
      prognosis and many times fatal, who have been growing in the last two decades
      with possibilities to be continue in all the world until 2020, showing use of pic
      asbestos to the years 1960/1970. Next 35 years the previsions of the deaths is
      more than 250 000. In Portugal (ROR) incidence is 1,2/1 000 000/year for total of
      the patients. Until now any new therapy showed advantage in the median survival
      and time to progression. The more important change whose the news than the
      antifolatos, particularly pemetrexed in combination with cisplatinum were actives
      in MM. Chemoterapy as soon as possible and second lines treatment it is very
      important thinking in the survival this fatal tumor. Rev Port Pneumol 2008; XIV
      (Sup.2): S35-S44. 

PMID- 25967567
TI  - New directions in the second line treatment of non-small cell lung cancers and in
      the management of malignant pleural mesotheliomas.

PMID- 25967568
TI  - Pemetrexed in second line treatment of non-small cell lung cancer - The
      portuguese experience.
AB  - Until 2004, docetaxel in monotherapy was the standard for second-line treatment
      of non-small cell lung cancer (NSCLC). Pemetrexed (P) has shown similar activity
      in this setting with a better adverse event profile. In Portugal, it was
      introduced in October of 2004. We have carried out a retrospective analysis of
      patients (pts) who received P for second-line NSCLC in Portugal from October 2004
      to December 2006. Data were collected from the records of pts with locally
      advanced or metastatic NSCLC and failed first-line chemotherapy enrolled in
      centers participating in the Portuguese Lung Cancer Study Group (GECP). Objective
      response (OR; complete [CR] or partial [PR] response) was evaluated using RECIST
      and safety was assessed using serious or non-serious adverse events (SAEs/AEs).
      By December 2006, 19 GECP centers had enrolled 244 pts who had received P for
      >=1cycle, and were considered evaluable for both objective response and safety.
      Demography: male/female, 175/69; median age, 57.0years (range 20-81); smoking
      status, y/ex/n, 116/57/71; adenocarcinoma / squamous-cell carcinoma/other
      histology, 141/72/31; mean time to progression (TTP) 8.07months. Disease control
      in 209 evaluable pts was observed in 116 (55.5%): 2 CR, 45 PR and 69 SD; mean TTP
      4.70months. The majority of AEs were grade 3 anemia (15 pts) and neutropenia (18
      pts). The mean overall survival was 17.27months. Our retrospective analysis has
      observed a similar disease control rate with P in 2nd line (55.5%), and TTP
      (4.7months) in our current unselected population to that published in the
      literature. P is an option for second-line NSCLC with a good tolerability. Rev
      Port Pneumol 2008; XIV (Sup.2): S9-S20. 

PMID- 25967570
TI  - Current clinical practice of transesophageal echocardiography and cardiac
      computed tomography prior to atrial fibrillation ablation in Canada.

PMID- 25967571
TI  - Effects of TRPV1 on the hippocampal synaptic plasticity in the epileptic rat
      brain.
AB  - Temporal lobe epilepsy is often presented by medically intractable recurrent
      seizures due to dysfunction of temporal lobe structures, mostly the temporomesial
      structures. The role of transient receptor potential vaniloid 1 (TRPV1) activity
      on synaptic plasticity of the epileptic brain tissues was investigated. We
      studied hippocampal TRPV1 protein content and distribution in the hippocampus of
      epileptic rats. Furthermore, the effects of pharmacologic modulation of TRPV1
      receptors on field excitatory postsynaptic potentials have been analyzed after
      induction of long term potentiation (LTP) in the hippocampal CA1 and CA3 areas
      after 1 day (acute phase) and 3 months (chronic phase) of pilocarpine-induced
      status epilepticus (SE). A higher expression of TRPV1 protein in the hippocampus
      as well as a higher distribution of this channel in CA1 and CA3 areas in both
      acute and chronic phases of pilocarpine-induced SE was observed. Activation of
      TRPV1 using capsaicin (1 uM) enhanced LTP induction in CA1 region in non
      epileptic rats. Inhibition of TRPV1 by capsazepine (10 uM) did not affect LTP
      induction in non-epileptic rats. In acute phase of SE, activation of TRPV1
      enhanced LTP in both CA1 and CA3 areas but TRPV1 inhibition did not affect LTP.
      In chronic phase of SE, application of TRPV1 antagonist enhanced LTP induction in
      CA1 and CA3 regions but TRPV1 activation had no effect on LTP. These findings
      indicate that a higher expression of TRPV1 in epileptic conditions is accompanied
      by a functional impact on the synaptic plasticity in the hippocampus. This
      suggests TRPV1 as a potential target in treatment of seizure attacks.

PMID- 25967572
TI  - White Matter Damage Relates to Oxygen Saturation in Children With Sickle Cell
      Anemia Without Silent Cerebral Infarcts.
AB  - BACKGROUND AND PURPOSE: Sickle cell anemia is associated with compromised oxygen
      carrying capability of hemoglobin and a high incidence of overt and silent
      stroke. However, in children with no evidence of cerebral infarction, there are
      changes in brain morphometry relative to healthy controls, which may be related
      to chronic anemia and oxygen desaturation. METHODS: A whole-brain tract-based
      spatial statistics analysis was carried out in 25 children with sickle cell
      anemia with no evidence of abnormality on T2-weighted magnetic resonance imaging
      (13 male, age range: 8-18 years) and 14 age- and race-matched controls (7 male,
      age range: 10-19 years) to determine the extent of white matter injury. The
      hypotheses that white matter damage is related to daytime peripheral oxygen
      saturation and steady-state hemoglobin were tested. RESULTS: Fractional
      anisotropy was found to be significantly lower in patients in the subcortical
      white matter (corticospinal tract and cerebellum), whereas mean diffusivity and
      radial diffusivity were higher in patients in widespread areas. There was a
      significant negative relationship between radial diffusivity and oxygen
      saturation (P<0.05) in the anterior corpus callosum and a trend-level negative
      relationship between radial diffusivity and hemoglobin (P<0.1) in the midbody of
      the corpus callosum. CONCLUSIONS: These data show widespread white matter
      abnormalities in a sample of asymptomatic children with sickle cell anemia, and
      provides for the first time direct evidence of a relationship between brain
      microstructure and markers of disease severity (eg, peripheral oxygen saturation
      and steady-state hemoglobin). This study suggests that diffusion tensor imaging
      metrics may serve as a biomarker for future trials of reducing hypoxic exposure.

PMID- 25967573
TI  - Time-Dependent Thrombus Resolution After Tissue-Type Plasminogen Activator in
      Patients With Stroke and Mice.
AB  - BACKGROUND AND PURPOSE: We investigated the relationship between the degree of
      thrombus resolution and the time from stroke onset or thrombus formation to
      intravenous tissue-type plasminogen activator (tPA) treatment. METHODS: In
      patients with stroke, we measured thrombus volume on thin-section noncontrast
      brain computed tomographic scans taken at baseline and 1 hour after tPA
      administration. We determined the association between the time from symptom onset
      to tPA treatment and the degree of thrombus resolution. In a C57/BL6 mouse model
      of FeCl3-induced carotid artery thrombosis, we investigated the effect of tPA
      administered at different time intervals after thrombus formation, using Doppler
      based blood flow measurement. RESULTS: Of 249 patients enrolled, 171 showed
      thrombus on baseline computed tomography. Thrombus was resolved by >=50% in 43
      patients (25.1%, good volume reduction) and by <50% in 94 patients (55.0%,
      moderate volume reduction) 1 hour after tPA treatment. In 34 patients (19.9%,
      nonvolume reduction; either no change or thrombus volume increased), overall
      thrombus volume increased. The probability of thrombus resolution decreased as
      the time interval from symptom onset to treatment increased. On multivariate
      analysis, good volume reduction was independently related with shorter time
      intervals from symptom onset to tPA treatment (odds ratio, 0.986 per minute
      saved; 95% confidence interval, 0.974-0.999). In the mouse model, as the interval
      between thrombus formation and tPA treatment increased, the initiation of
      recanalization was delayed (P=0.006) and the frequency of final recanalization
      decreased (P for trends=0.006). CONCLUSIONS: Early administration of tPA after
      stroke onset is associated with better thrombus resolution.

PMID- 25967574
TI  - Diet and Stroke: Recent Evidence Supporting a Mediterranean-Style Diet and Food
      in the Primary Prevention of Stroke.

PMID- 25967575
TI  - Perivascular adipose adiponectin correlates with symptom status of patients
      undergoing carotid endarterectomy.
AB  - BACKGROUND AND PURPOSE: Recent symptoms stand as a major determinant of stroke
      risk in patients with carotid stenosis, likely reflective of atherosclerotic
      plaque destabilization. In view of emerging links between vascular and adipose
      biology, we hypothesized that human perivascular adipose characteristics
      associate with carotid disease symptom status. METHODS: Clinical history, carotid
      plaques, blood, and subcutaneous and perivascular adipose tissues were
      prospectively collected from patients undergoing carotid endarterectomy. Nine
      adipose-associated biological mediators were assayed and compared in patients
      with symptomatic (n=15) versus asymptomatic (n=19) disease. Bonferroni correction
      was performed for multiple testing (alpha/9=0.006). RESULTS: Symptomatic patients
      had 1.9-fold higher perivascular adiponectin levels (P=0.005). Other circulating,
      subcutaneous, and perivascular biomarkers, as well as microscopic plaque
      characteristics, did not differ between symptomatic and asymptomatic patients.
      CONCLUSIONS: Symptomatic and asymptomatic carotid endarterectomy patients display
      a tissue-specific difference in perivascular adipose adiponectin. This
      difference, which was not seen in plasma or subcutaneous compartments, supports a
      potential local paracrine relationship with vascular disease processes that may
      be related to stroke mechanisms.

PMID- 25967577
TI  - Organizational Update: World Stroke Organization.

PMID- 25967576
TI  - Stroke Induces Nuclear Shuttling of Histone Deacetylase 4.
AB  - BACKGROUND AND PURPOSE: Histone deacetylases (HDACs) 4 and 5 are abundantly
      expressed in the brain and have been implicated in the regulation of
      neurodegeneration. Under physiological conditions, HDACs 4 and 5 are expressed in
      the cytoplasm of brain cells where they cannot directly access chromatin. In
      response to external stimuli, they can shuttle to the nucleus and regulate gene
      expression. However, the effect of stroke on nuclear shuttling of HDACs 4 and 5
      remains unknown. METHODS: Using a rat model of middle cerebral artery occlusion,
      we examined the subcellular localization of HDACs 4 and 5 in the peri-infarct
      cortex during brain repair after stroke. RESULTS: Stroke significantly increased
      nuclear HDAC4 immunoreactivity in neurons, but not in astrocytes or in
      oligodendrocytes, of the peri-infarct cortex at 2, 7, and 14 days after middle
      cerebral artery occlusion. Neurons with nuclear HDAC4 immunoreactivity
      distributed across all layers of the peri-infarct cortex and were Ctip2+
      excitatory and parvalbumin+ inhibitory neurons. These neurons were not TUNEL or
      BrdU positive. Furthermore, nuclear HDAC4 immunoreactivity was positively and
      significantly correlated with increased dendritic, axonal, and myelin densities
      as determined by microtubule-associated protein 2, phosphorylated neurofilament
      heavy chain, and myelin basic protein, respectively. Unlike HDAC4, stroke did not
      alter nuclear localization of HDAC5. CONCLUSIONS: Our data show that stroke
      induces nuclear shuttling of HDAC4 in neurons in the peri-infarct cortex, and
      that increased nuclear HDAC4 is strongly associated with neuronal remodeling but
      not with neuronal cell death, suggesting a role for nuclear HDAC4 in promoting
      neuronal recovery after ischemic injury.

PMID- 25967578
TI  - Cryptic Loss of Consciousness in a 36-Year-Old Woman.

PMID- 25967579
TI  - Enhancing public health practice through a capacity-building educational
      programme: an evaluation.
AB  - BACKGROUND: The Post-Graduate Diploma in Public Health Management, launched by
      the Govt. of India under the aegis of the National Rural Health Mission in 2008,
      aims to enhance the managerial capabilities of public health professionals to
      improve the public health system. The Govt. of India invested enormous resources
      into this programme and requested an evaluation to understand the current
      processes, assess the graduates' work performance and identify areas for
      improvement. METHODS: Quantitative telephone surveys as well as qualitative in
      depth interviews were used. Graduates from the first three batches, their
      supervisors, peers and subordinates and faculty members were interviewed.
      Quantitative data were analysed using proportions, means and interpretative
      descriptions. Qualitative analyses involved transcription, translation, sorting,
      coding and filing into domains. RESULTS: Of the 363 graduates whose contact
      details were available, 138 could not be contacted. Two hundred twenty-three
      (223) graduates (61.43% of eligible participants) were interviewed by telephone;
      52 in-depth interviews were conducted. Of the graduates who joined, 63.8%
      graduates were motivated to join the programme for career advancement and gaining
      public health knowledge. The content was theoretically good, informative and well
      designed. Graduates expressed need for more practical and group work. After
      graduating, they reported being equipped with some new skills to implement
      programmes effectively. They reported that attitudes and healthcare delivery
      practices had improved; they had better self-esteem, increased confidence, better
      communication skills and implementation capacity. While they were able to apply
      some skills, they encountered some barriers, such as governance, placements, lack
      of support from the system and community, inadequate implementation authority and
      lack of planning by the state government. Incentives (both monetary and non
      monetary) played a major role in motivating them to deliver public health
      services. They suggested that states should nominate candidates expected to make
      a significant contribution to the health system, recognition from a relevant
      authoritative national body and need for a placement cell, especially for the
      self-sponsored candidates. CONCLUSIONS: A continuous mechanism for interaction
      and dialogue with the graduates during and after completion of the programme
      should be designed. This evaluation helped by providing inputs for refining the
      programme.

PMID- 25967580
TI  - Design and assembly of supramolecular dual-modality nanoprobes.
AB  - We report the design and synthesis of self-assembling dual-modality molecular
      probes containing both a fluorophore for optical imaging and a metal ion chelator
      for imaging with MRI or radionuclide methods. These molecular probes can
      spontaneously associate into spherical nanoparticles under physiological
      conditions. We demonstrate the use of these supramolecular nanoprobes for live
      cell optical imaging, as well as their potential use as MRI contrast agents after
      complexation with gadolinium. Our results suggest that self-assembly into
      supramolecular nanoprobes presents an effective means to enhance and tune the
      relaxivities of molecular probes. 

PMID- 25967581
TI  - Ex vivo and in vivo modulatory effects of umbilical cord Wharton's jelly stem
      cells on human oral mucosa stroma substitutes.
AB  - Novel oral mucosa substitutes have been developed in the laboratory using human
      umbilical cord Wharton's jelly stem cells -HWJSC- as an alternative cell source.
      In the present work, we have generated human oral mucosa substitutes with oral
      mucosa keratinocytes and HWJSC to determine the influence of these cell sources
      on stromal differentiation. First, acellular and cellular stroma substitutes and
      bilayered oral mucosa substitutes with an epithelial layer consisting of oral
      mucosa keratinocytes -OM samples- or HWJSC -hOM- were generated. Then, tissues
      were analyzed by light and electron microscopy, histochemistry and
      immunohistochemistry to quantify all major extracellular matrix components after
      1, 2 and 3 weeks of ex vivo development, and OM and hOM were also analyzed after
      in vivo grafting. The results showed that bioengineered oral mucosa stromas
      displayed an adequate fibrillar mesh. Synthesis of abundant collagen fibers was
      detected in OM and hOM after 3 weeks, and in vivo grafting resulted in an
      increased collagen synthesis. No elastic or reticular fibers were found.
      Glycoprotein synthesis was found at the epithelial-stromal layer when samples
      were grafted in vivo. Finally, proteoglycans, decorin, versican and aggrecan were
      strongly dependent on the in vivo environment and the presence of a well
      structured epithelium on top. The use of HWJSC was associated to an increased
      synthesis of versican. These results confirm the usefulness of fibrin-agarose
      biomaterials for the generation of an efficient human oral mucosa stroma
      substitute and the importance of the in vivo environment and the epithelial
      mesenchymal interaction for the adequate differentiation of the bioengineered
      stroma. 

PMID- 25967583
TI  - LC-ESI-MS/MS analysis and pharmacokinetics of heterophyllin B, a cyclic
      octapeptide from Pseudostellaria heterophylla in rat plasma.
AB  - Heterophyllin B (HB) is a cyclic octapeptide isolated from Pseudostellaria
      heterophylla. HB is used as the quality control index for evaluating P.
      heterophylla in the Chinese Pharmacopoeia. A rapid and sensitive LC-ESI-MS/MS
      method was developed and validated for the analysis of HB in rat plasma. Sample
      preparation consisted of a solid-phase extraction step for the removal of
      interference and preconcentration of the target analyte HB and the internal
      standard N-acetylcysteine before chromatographic analysis by MS/MS detection. The
      separation of HB and N-acetylcysteine was performed using a Hypersil GOLDTM C18
      column and a mixture of methanol-water (60:40, v/v) containing 10 mmol/L ammonium
      formate and 0.1% formic acid as the mobile phase. The determination step was
      optimized in the selected reaction monitoring mode for the highly selective and
      sensitive quantitation of HB in rat plasma. Intra- and inter-assay precision (as
      relative standard deviation) was <=9.1%, and accuracy was between 92.6 and
      102.7%. The validated method was successfully applied to quantify HB
      concentrations up to 7 h after tail intravenous injections of 2.08, 4.16 and 8.32
      mg/kg HB in rats. The LC-MS/MS method identified the relevant pharmacokinetic
      parameters of HB and its studied analog.

PMID- 25967582
TI  - Heightened Temporal Summation of Pain in Patients with Functional
      Gastrointestinal Disorders and History of Trauma.
AB  - BACKGROUND: Individuals with functional gastrointestinal disorders (FGIDs) report
      experiencing trauma more often than healthy controls, but little is known
      regarding psychophysical correlates. PURPOSE: The purpose of this study was to
      test the hypothesis that adolescents and young adults with FGIDs since childhood
      and a trauma history (n = 38) would exhibit heightened temporal summation to
      thermal pain stimuli, an index of central sensitization, and greater clinical
      symptoms compared to patients with FGIDs and no trauma history (n = 95) and
      healthy controls (n = 135). METHODS: Participants completed self-report measures,
      an experimental pain protocol, and psychiatric diagnostic interview as part of a
      larger longitudinal study. RESULTS: FGID + Trauma patients exhibited greater
      temporal summation than FGID + No Trauma patients and healthy controls.
      Additionally, FGID + Trauma patients exhibited greater gastrointestinal and non
      gastrointestinal symptom severity, number of chronic pain sites, and disability.
      CONCLUSIONS: Assessing for trauma history in patients with FGIDs could identify a
      subset at risk for greater central sensitization and pain-related symptoms.

PMID- 25967584
TI  - Examining a sample of Black deaf individuals on the Deaf Acculturation Scale.
AB  - The current study sought to identify and analyze how Black deaf and hard-of
      hearing people conceptualize their deaf and hard-of-hearing identities. That is,
      what cultural and linguistic factors are involved and how do they interact? An
      existing measure of Deaf cultural identity, the Deaf Acculturation Scale (DAS),
      was used to evaluate these questions. Review of the measure's normative sample (n
      = 3,070) indicated that fewer than 300 self-identified as racial/ethnic
      minorities (Hispanic/Latino, Black, or Asian). Results of a preliminary study
      revealed that Non-White deaf individuals responded to DAS items in ways that
      significantly differed from responses provided by White deaf individuals.
      Moreover, the existing 5-factor correlated model of the DAS did not fit well with
      the Non-White group. The current study administered the DAS to a new sample of
      106 Black deaf individuals. Principal components analysis determined an
      appropriate factor structure for this population. In addition to the existing 5
      factors, a sixth factor emerged that appears to reflect identity concerns
      specific to Black deaf people. Ideas for future research, including how to
      examine the intersections of Deaf identity and racial identity, are discussed. 

PMID- 25967585
TI  - Carotid Arterial Hemodynamic in Ischemic Levkoaraiosis Suggests Hypoperfusion
      Mechanism.
AB  - BACKGROUND: Leukoaraiosis (ILA) is believed to be ischaemic in origin due to its
      similar location as that of lacunar infarctions and its association with
      cerebrovascular risk factors. However, its pathophysiology is not well
      understood. The ischaemic injuries may be a result of increased pulsatility or
      cerebral hypo-perfusion. We used carotid duplex ultrasound to prove that the
      underlying mechanism is hypo-perfusion. METHODS: We compared 55 ILA patients to
      44 risk factor-matched controls with normal magnetic resonance imaging (MRI) of
      the head. ILA diagnosis was based on MRI and was further categorised according to
      the Fazekas scale. We measured carotid artery blood flow velocity and diameter
      and calculated carotid blood flow and resistance indexes. RESULTS: Blood flow
      velocities and blood flows were significantly lower in the ILA group, including
      diastolic, systolic and mean pressures (p <= 0.05). The resistance indices were
      higher in the ILA group, but the differences were not statistically significant.
      All the velocities and blood flows showed a decreasing trend with higher Fazekas
      score, whereas resistance indexes showed an increasing trend. CONCLUSIONS: Lower
      blood flow and higher resistance of carotid arteries are consistent with the hypo
      perfusion theory of ILA. Carotid ultrasound could have a diagnostic and
      prognostic role in ILA patients.

PMID- 25967586
TI  - High temporal resolution dynamic contrast-enhanced MRI using compressed sensing
      combined sequence in quantitative renal perfusion measurement.
AB  - PURPOSE: To demonstrate the feasibility of the improved temporal resolution by
      using compressed sensing (CS) combined imaging sequence in dynamic contrast
      enhanced MRI (DCE-MRI) of kidney, and investigate its quantitative effects on
      renal perfusion measurements. MATERIALS AND METHODS: Ten rabbits were included in
      the accelerated scans with a CS-combined 3D pulse sequence. To evaluate the image
      quality, the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were
      compared between the proposed CS strategy and the conventional full sampling
      method. Moreover, renal perfusion was estimated by using the separable
      compartmental model in both CS simulation and realistic CS acquisitions. RESULTS:
      The CS method showed DCE-MRI images with improved temporal resolution and
      acceptable image contrast, while presenting significantly higher SNR than the
      fully sampled images (p<.01) at 2-, 3- and 4-X acceleration. In quantitative
      measurements, renal perfusion results were in good agreement with the fully
      sampled one (concordance correlation coefficient=0.95, 0.91, 0.88) at 2-, 3- and
      4-X acceleration in CS simulation. Moreover, in realistic acquisitions, the
      estimated perfusion by the separable compartmental model exhibited no significant
      differences (p>.05) between each CS-accelerated acquisition and the full sampling
      method. CONCLUSION: The CS-combined 3D sequence could improve the temporal
      resolution for DCE-MRI in kidney while yielding diagnostically acceptable image
      quality, and it could provide effective measurements of renal perfusion.

PMID- 25967587
TI  - The experience of caregivers of people living with serious mental disorders: a
      study from rural Ghana.
AB  - BACKGROUND: Families and friends who give care to people with mental disorders
      (MDs) are affected in a variety of ways and degrees. The interplay of caregiving
      consequences: poverty, discrimination and stigma, lack of support from others,
      diminished social relationships, depression, emotional trauma, and poor or
      interrupted sleep are associated caregiver burden. OBJECTIVE: The burden of care
      on caregivers of people living with MDs was assessed in two districts located in
      the middle part of Ghana. Coping strategies and available support for caregivers
      of MDs were also assessed. DESIGN: A qualitative study was carried out involving
      75 caregivers of participants with MDs registered within the Kintampo Health and
      Demographic Surveillance Systems. Data were gathered from caregivers about their
      experiences in providing care for their relations with MDs. RESULTS: Caregivers
      reported various degrees of burden, which included financial, social exclusion,
      emotional, depression, and inadequate time for other social responsibilities.
      Responsibilities around caregiving were mostly shared among close relatives but
      to a varying and limited extent. Religious prayers and the anticipation of cure
      were the main coping strategies adopted by caregivers, with expectation of new
      treatments being discovered. CONCLUSIONS: Emotional distress, stigma, financial
      burden, lack of support networks, social exclusion, health impact, and absence of
      decentralised mental health services were experienced by family caregivers. These
      findings highlight the need for interventions to support people with MDs and
      their caregivers. This might include policy development and implementation that
      will decentralise mental health care provision including psychosocial support for
      caregivers. This will ameliorate families' financial and emotional burden,
      facilitate early diagnosis and management, reduce travel time to seek care, and
      improve the quality of life of family caregivers of persons with MDs.

PMID- 25967588
TI  - Reduced gland mucin-specific O-glycan in gastric atrophy: A possible risk factor
      for differentiated-type adenocarcinoma of the stomach.
AB  - BACKGROUND AND AIMS: O-glycans exhibiting terminal alpha1,4-linked N
      acetylglucosamine (alphaGlcNAc) are attached to MUC6 in gastric gland mucins and
      serve as a tumor suppressor for gastric adenocarcinoma. Gastric atrophy is
      associated with risk for gastric cancer. However, the significance of alphaGlcNAc
      expression in pyloric glands of chronic atrophic gastritis remains unknown. Here,
      we asked whether reduced alphaGlcNAc expression in chronic atrophic gastritis is
      associated with risk for gastric cancer. METHODS: We quantitatively analyzed
      expression of alphaGlcNAc relative to MUC6 in pyloric glands by
      immunohistochemistry in 67 patients with normal mucosa, 70 with chronic atrophic
      gastritis, 68 with intramucosal differentiated-type adenocarcinoma, and 11 with
      intramucosal undifferentiated-type adenocarcinoma. We also compared the Ki-67
      labeling index in gastric epithelial cells between chronic atrophic gastritis and
      normal gastric mucosa with respect to alphaGlcNAc reduction. RESULTS: In normal
      pyloric mucosa, alphaGlcNAc was co-expressed with MUC6. By contrast, in chronic
      atrophic gastritis, pyloric gland alphaGlcNAc expression was significantly
      reduced relative to MUC6. In intramucosal gastric cancer, alphaGlcNAc expression
      in pyloric glands found just beneath differentiated-type adenocarcinoma was also
      reduced relative to MUC6. However, pyloric glands present beneath
      undifferentiated-type adenocarcinoma exhibited no alphaGlcNAc decrease. The Ki-67
      labeling index in chronic atrophic gastritis showing alphaGlcNAc reduction was
      significantly increased relative to that in normal gastric mucosa. CONCLUSIONS:
      Because alphaGlcNAc prevents the gastric cancer development, reduced alphaGlcNAc
      expression in chronic atrophic gastritis is a possible risk factor for
      differentiated-type adenocarcinoma of the stomach.

PMID- 25967589
TI  - Efficient assembly of oligomannosides using the hydrophobically assisted
      switching phase method.
AB  - The hydrophobically assisted switching phase (HASP) method was applied in the
      assembly of oligomannosides. A new mannosyl donor with high reactivity was
      selected after a series of optimization studies, which was suitable for the
      synthesis of oligomannosides via the HASP method. The practicability of the HASP
      method towards the synthesis of branched oligosaccharides was explored and two
      branched penta-mannosides were assembled efficiently. 

PMID- 25967590
TI  - Periodic tiling of triangular and square nanotubes in a cationic metal-organic
      framework for selective anion exchange.
AB  - A unique cationic metal-organic framework was synthesized by connecting the
      neutral rod-shaped secondary building unit with a cationic dicarboxylate ligand.
      This framework showed a rare snub square tessellation pattern by the periodic
      tiling of triangular and square nanotubes. The charge- and size-dependent ion
      exchange of anion dyes was investigated. 

PMID- 25967591
TI  - An analysis of dental patient safety incidents in a patient complaint and
      healthcare supervisory database in Finland.
AB  - OBJECTIVE: Few studies of patient harm and harm-prevention methods in dentistry
      exist. This study aimed to identify and characterize dental patient safety
      incidents (PSIs) in a national sample of closed dental cases reported to the
      Regional State Administrative Agencies (AVIs) and the National Supervisory
      Authority for Welfare and Health (Valvira) in Finland. MATERIALS AND METHODS: The
      sample included all available fully resolved dental cases (n = 948) during 2000
      2012 (initiated by the end of 2011). Cases included both patient and next of kin
      complaints and notifications from other authorities, employers, pharmacies, etc.
      The cases analyzed concerned both public and private dentistry and included
      incident reports lodged against dentists and other dental-care professionals.
      Data also include the most severe cases since these are reported to Valvira. PSIs
      were categorized according to common incident types and preventability and
      severity assessments were based on expert opinions in the decisions from closed
      cases. RESULTS: Most alleged PSIs were proven valid and evaluated as potentially
      preventable. PSIs were most often related to different dental treatment
      procedures or diagnostics. More than half of all PSIs were assessed as severe,
      posing severe risk or as causing permanent or long-lasting harm to patients. The
      risk for PSI was highest among male general dental practitioners with recurring
      complaints and notifications. CONCLUSIONS: Despite some limitations, this
      register-based study identifies new perspectives on improving safety in dental
      care. Many PSIs could be prevented through the proper and more systematic use of
      already available error-prevention methods.

PMID- 25967592
TI  - Aza-nickelacycle key intermediate in nickel(0)-catalyzed transformation
      reactions.
AB  - This Perspective provides an overview of the oxidative cyclization reactions of
      alkynes and imines with nickel(0) to give five-membered aza-nickelacycles. These
      reactions could be a key step in multicomponent coupling and cycloaddition
      reactions to afford nitrogen-containing organic compounds. 

PMID- 25967593
TI  - The impact of PCR in the management of prosthetic joint infections.
AB  - An accurate diagnosis of prosthetic joint infection (PJI) remains a challenging
      clinical problem and is essential for the success of treatment regardless of the
      treatment option chosen by patients and surgeons. In recent years, PCR for the
      diagnosis of PJI has received much attention. Here, we review the impact of
      common PCR-based techniques on identifying causative organisms, antibiotic
      management and economics of PJI. 

PMID- 25967595
TI  - SIRT1 attenuates PAF-induced MMP-2 production via down-regulation of PAF receptor
      expression in vascular smooth muscle cells.
AB  - Silent mating type information regulation 2 homolog 1 (SIRT1) is known as a key
      regulator in the protection of various vascular disorders, however, no direct
      evidences have been reported in the progression of atherosclerosis. Considering
      the pivotal role of matrix metalloproteinase-2 (MMP-2) in plaque destabilization,
      this study investigated the role of SIRT1 on MMP-2 production in vascular smooth
      muscle cells (VSMCs) induced by platelet activating factor (PAF, 1-O-alkyl-2
      acetyl-sn-glycero-3-phosphocholine). In VSMCs stimulated with resveratrol, SIRT1
      activator, PAF receptor (PAFR) was internalized and then its protein levels were
      diminished. It was attenuated in cells pretreated with proteasome or lysosome
      inhibitor. Also, the degradation of PAFR in SIRT1-stimulated cells was
      significantly attenuated by beta-arrestin2 depletion. In cells treated with
      nicotinamide, SIRT1 deacetylase inhibitor, PAFR internalization by resveratrol or
      reSIRT1 was inhibited, demonstrating that deacetylation of SIRT1 is an important
      step in SIRT1-induced PAFR down-regulation. Moreover, PAF-induced MMP-2
      production in VSMCs and aorta was attenuated by resveratrol. In the aorta of
      SIRT1 transgenic mice, the PAF-induced MMP-2 expression was prominently
      attenuated compared to that in wild type mice. Taken together, it was suggested
      that SIRT1 down-regulated PAFR in VSMCs via beta-arrestin2-mediated
      internalization and degradation, leading to an inhibition of PAF-induced MMP-2
      production. 

PMID- 25967596
TI  - LMA, density and thickness: recognizing different leaf shapes and correcting for
      their nonlaminarity.

PMID- 25967594
TI  - Growth factor-eluting technologies for bone tissue engineering.
AB  - Growth factors are essential orchestrators of the normal bone fracture healing
      response. For non-union defects, delivery of exogenous growth factors to the
      injured site significantly improves healing outcomes. However, current clinical
      methods for scaffold-based growth factor delivery are fairly rudimentary, and
      there is a need for greater spatial and temporal regulation to increase their in
      vivo efficacy. Various approaches used to provide spatiotemporal control of
      growth factor delivery from bone tissue engineering scaffolds include physical
      entrapment, chemical binding, surface modifications, biomineralization, micro-
      and nanoparticle encapsulation, and genetically engineered cells. Here, we
      provide a brief review of these technologies, describing the fundamental
      mechanisms used to regulate release kinetics. Examples of their use in pre
      clinical studies are discussed, and their capacities to provide tunable, growth
      factor delivery are compared. These advanced scaffold systems have the potential
      to provide safer, more effective therapies for bone regeneration than the systems
      currently employed in the clinic. 

PMID- 25967598
TI  - Resilience as a predictor for emotional response to the diagnosis and surgery in
      breast cancer patients.
AB  - OBJECTIVE: The purposes of the present study were to investigate the role of
      resilience in the prediction of emotional response in breast cancer patients and
      to examine whether this association is specific for women undergoing this
      emotionally taxing condition or whether resilience is more generally associated
      with higher levels of emotional well-being. METHODS: Two hundred fifty-three
      breast cancer patients and 211 healthy female controls completed four
      psychological questionnaires. Measures comprised the Connor-Davidson Resilience
      Scale, the Hospital Anxiety and Depression Scale, Positive and Negative Affect
      Schedule, and two happiness items. Cancer patients were assessed after diagnosis
      and surgery. RESULTS: Cancer patients reported higher levels of anxiety,
      depression, and negative affect and lower levels of positive affect and current
      happiness compared with control women. There was no difference between the two
      groups in level of resilience. Higher levels of resilience were related to better
      emotional adjustment both in women with breast cancer and in control women, but
      this association was stronger within the sample of cancer patients. In fact,
      patients scoring high on resilience seemed to experience similar levels of
      anxiety, depression, and current happiness as healthy women. CONCLUSION: Our
      results confirm that resilience may at least partially protect against emotional
      distress in cancer patients. Our findings suggest that resilience may be a
      relatively stable trait that is not affected by adversity.

PMID- 25967599
TI  - Quantifying insufficient coping behavior under chronic stress: a cross-cultural
      study of 1,303 students from Italy, Spain and Argentina.
AB  - The question of how to quantify insufficient coping behavior under chronic stress
      is of major clinical relevance. In fact, chronic stress increasingly dominates
      modern work conditions and can affect nearly every system of the human body, as
      suggested by physical, cognitive, affective and behavioral symptoms. Since
      freshmen students experience constantly high levels of stress due to tight
      schedules and frequent examinations, we carried out a 3-center study of 1,303
      students from Italy, Spain and Argentina in order to develop socioculturally
      independent means for quantifying coping behavior. The data analysis relied on 2
      self-report questionnaires: the Coping Strategies Inventory (COPE) for the
      assessment of coping behavior and the Zurich Health Questionnaire which assesses
      consumption behavior and general health dimensions. A neural network approach was
      used to determine the structural properties inherent in the COPE instrument. Our
      analyses revealed 2 highly stable, socioculturally independent scales that
      reflected basic coping behavior in terms of the personality traits activity
      passivity and defeatism-resilience. This replicated previous results based on
      Swiss and US-American data. The percentage of students exhibiting insufficient
      coping behavior was very similar across the study sites (11.5-18.0%). Given their
      stability and validity, the newly developed scales enable the quantification of
      basic coping behavior in a cost-efficient and reliable way, thus clearing the way
      for the early detection of subjects with insufficient coping skills under chronic
      stress who may be at risk of physical or mental health problems.

PMID- 25967597
TI  - Serum uric acid and the incidence of CKD and hypertension.
AB  - BACKGROUND: Uric acid (UA) levels correlate positively with the prevalence of
      chronic kidney disease (CKD) and/or hypertension. We tested the hypothesis that
      UA may also have a link to a new incidence of CKD and hypertension. METHODS:
      Study design is a cohort study and the predictor is UA levels. Of the 15,470
      screened cases, 8223 participants without CKD were eligible for the analysis of
      the incidence of CKD. Among these CKD candidates, 7569 participants were eligible
      for the analysis of the new development of hypertension. The observation period
      was 4 years. RESULTS: Relationship of UA with new cases of CKD. Higher UA levels
      had a closer association with the new development of CKD; 1.1 % (UA < 5 mg/dL),
      1.5 % (5.0-5.9 mg/dL), 1.7 % (6.0-6.9 mg/dL), and 3.4 % (?7 mg/dL), respectively
      (p < 0.001 by the Chi-square test). Cox proportional hazard analysis showed that
      the estimates of the CKD development were eGFR [Hazard Ratio (HR) 0.816, 95 %
      confidence intervals (CI) 0.791-0.840] and male gender (HR 0.562, 95 % CI 0.322
      0.982). UA levels and new development of hypertension. Higher UA levels had a
      closer association with the new development of hypertension; 5.0 % (UA < 5
      mg/dL), 8.9 % (5.0-5.9 mg/dL), 10.6 % (6.0-6.9 mg/dL), and 11.8 % (?7 mg/dL),
      respectively (p < 0.001 by the Chi-square test). Cox proportional hazard analysis
      showed that the estimates of the hypertension development were BMI (HR 1.190, 95
      % CI 1.155-1.226), age (HR 1.021, 95 % CI 1.010-1.032), HDL-cholesterol (HR
      1.013, 95 % CI 1.007-1.019), male gender (HR 1.791, 95 % CI 1.338-2.395), UA
      level (HR 1.112, 95 % CI 1.024-1.207), and eGFR (HR 1008, 95 % CI 1.002-1.013).
      Furthermore, the logistic analysis showed that the odds ratio (OR) to estimate
      hypertension in the high UA group (UA ? 7 mg/dL; OR 1.33, 95 % CI 1.01-1.80) was
      greater than that in the low UA group (UA < 5 mg/dL). Kaplan-Meier analysis also
      confirmed the finding that the higher the UA levels the greater the hypertension
      development (p < 0.001 by the Log-rank test and Cox proportional hazard
      analysis). CONCLUSION: High UA levels are associated with the new development of
      hypertension, but not with the incidence of CKD.

PMID- 25967600
TI  - [Quality assurance in interventional neuroradiology].

PMID- 25967601
TI  - Global Cognitive Impairment in Systemic Lupus Erythematosus Patients: A
      Structural MRI Study.
AB  - OBJECTIVE: This study investigated differences in subcortical brain volumes of
      SLE patients with cognitive deficits (SLE-CD) and SLE patients with normal
      cognitive performance (SLE-CN), regardless of the presence of other
      neuropsychiatric symptoms. METHOD: We studied 40 patients divided into two
      matched groups (SLE-CD n = 20; SLE-CN n = 20), with age ranging from 21 to 63
      years old (100 % female) and 14.73 +/- 10.18 years of diagnosis. Magnetic
      resonance imaging exams were performed on a 1.5 T scanner. A neuropsychological
      flexible battery was applied individually, including reasoning/problem-solving,
      praxis, episodic and working memory, processing speed, language/fluency,
      executive functions (inhibition and flexibility), and sustained attention. Z
      score <= - 2.0 in any dimension was considered as a cut-off for being considered
      to possess cognitive deficits. One-way analyses of covariance (ANCOVA) were
      performed to compare the brain structure volumes between groups. The analyses
      were controlled for the effects of lupus-related neuropsychiatric disorders.
      RESULTS: SLE patients with cognitive deficits had significantly smaller volumes
      in the left hippocampus, amygdala, and the right hippocampus than SLE patients
      without cognitive deficits. CONCLUSION: SLE patients with cognitive deficits
      appeared to have reduced temporal lobe structures when compared with SLE without
      cognitive deficits. These results corroborate a systems vulnerability model that
      investigated temporal lobe vulnerability during normal aging and in other
      neurological disorders.

PMID- 25967602
TI  - Freiburg Neuropathology Case Conference: An Infant with a Supratentorial Mass
      Lesion.

PMID- 25967603
TI  - Whole-Slide Imaging of Pap Cellblock Preparations Is a Potentially Valid
      Screening Method.
AB  - OBJECTIVE: To date, the impact of digital imaging on routine cytology remains far
      from perfect. Cellblock (CB) preparations from Pap samples have been shown to be
      diagnostically valuable. We evaluated the validity of utilizing whole-slide
      imaging (WSI) prepared from Pap CBs as a screening tool. STUDY DESIGN: A total of
      1,110 CB slides prepared from residual Pap samples were analyzed - 563 normal,
      282 atypical squamous cells of undetermined significance (ASCUS), 12 atypical
      squamous cells-cannot exclude high-grade squamous intraepithelial lesion, 188 low
      grade squamous intraepithelial lesions (LSIL), 36 high-grade squamous
      intraepithelial lesions (HSIL), 25 atypical glandular cells of undetermined
      significance, 1 adenocarcinoma in situ, 2 invasive adenocarcinomas, and 1
      squamous cell carcinoma. Virtual slides were obtained using the Aperio system.
      Test performance characteristics of liquid-based samples and WSI from CB samples
      were compared. RESULTS: Average sensitivity and specificity of the five WSI
      reviewers was 58.3 and 85.1% for ASCUS, respectively, 54.1 and 93.9% for LSIL,
      and 51.8 and 98.8% for HSIL. Overall WSI sensitivity and specificity for
      detecting lesions was 82.1 and 86.2%, respectively. Agreement (kappa values)
      between WSI reviewers was 0.56 for ASCUS, 0.69 for LSIL, 0.67 for HSIL, and 0.74
      for negative samples. CONCLUSIONS: WSI of CB preparations is a feasible method to
      achieve high-quality specimen preparations. It is as sensitive as liquid-based
      methods and appears to be highly specific for the detection of LSIL and HSIL.

PMID- 25967604
TI  - Investigations into cytotoxic effects of the herbal preparation Abnormal Savda
      Munziq.
AB  - OBJECTIVE: To evaluate the effects of Abnormal Savda Munziq (ASMq), a traditional
      herbal medicine, for the prevention and treatment of human diseases, e.g. bowel
      cancer. METHODS: The parameters total polyphenol content, cell proliferation and
      DNA-damage as well as RNA and protein-oxidation were analysed in vitro. Besides,
      the expressions of miRNA and tumor suppressor genes as well as cellular
      senescence were evaluated. RESULTS: ASMq had a high polyphenol content and
      induced damage to proteins, RNA as well as to DNA, which is correlated with its
      cytotoxicity. Furthermore ASMq up-regulated the tumor suppressor genes p21, p53
      and p16 and down-regulated the micro-RNAs hsa-mir-17 and hsa-mir-106b. In
      addition cellular growth arrest and SA-beta-gal-staining were induced.
      CONCLUSION: ASMq has the ability to induce DNA damage and cellular senescence,
      which are double-edged mechanisms in fighting cancer, as they might also have
      harmful side effects.

PMID- 25967605
TI  - Education of Chinese medicine tongue diagnosis by automatic tongue diagnosis
      system.
AB  - OBJECTIVE: To investigate the efficacy of applying automatic tongue diagnosis
      system (ATDS) to the training of novice Chinese medicine (CM) doctors in the
      tongue diagnosis. METHOD: A two-round experiment composed of pre- and after
      training tests was performed. Two groups of CM doctors were formed by experienced
      doctors (ED) and novice doctors (ND). The intra- and inter-observer agreements
      for the ED and ND groups, and the inter-observer agreements between ATDS and ED,
      and ATDS and ND were derived first. After a 1-month training of the ND, the intra
      and inter-observer agreements of the ND group, and the inter-observer agreement
      between ATDS and ND were obtained. RESULT: The kappa value of agreement data for
      ND after training was significantly higher than ND before training with a level
      of P<0.05, indicating an obvious improvement of intra-observer agreement for ND
      after training with ATDS. The inter-observer agreements for the ED group, and ND
      group after training were significantly higher (P<0.05) than the ND group before
      training. In contrast, no significance is observed between the ED group and the
      ND group after training, indicating that physicians in the ND group achieve an
      inter-observer agreement to the same level as that of ED after 1-month training.
      CONCLUSION: This finding validates the utilization of ATDS as a mean of education
      in forging consensus during the learning process of tongue diagnosis.

PMID- 25967606
TI  - Effects of Korean red ginseng on semen parameters in male infertility patients: A
      randomized, placebo-controlled, double-blind clinical study.
AB  - OBJECTIVE: To investigate the effects of Korean red ginseng (KRG) on semen
      parameters in male infertility patients in a randomized, double-blind, placebo
      controlled study. METHODS: A total of 80 male infertility patients with
      varicocele were recruited from April 2011 to February 2012. The subjects were
      then divided into the following four groups: non-varicocelectomy (V)+placebo (P)
      group, V+P group, non-V+KRG group (1.5-g KRG daily), and V+KGR group (1.5-g KRG
      daily). Semen analysis was performed and hormonal levels were measured in each
      treatment arm after 12 weeks. RESULTS: All groups but not the non-V+P group,
      showed significant improvements in sperm concentrations, motility, morphology,
      and viability at the end of the study. However, there were no significant
      differences in serum follicle-stimulating hormone, luteinizing hormone, and
      testosterone among groups. The incidence of adverse events was low, and all
      events were assumed to be unrelated to the treatments administered. CONCLUSIONS:
      Although the exact mechanism by which KRG improves spermatogenesis remains
      unclear, KRG may be a useful agent for the treatment of male infertility.
      Nevertheless, additional studies to evaluate the optimal dose and duration of
      treatment are needed.

PMID- 25967607
TI  - Effects of Hedan Tablet () on lipid profile, proprotein convertase
      subtilisin/kexin type 9 and high-density lipoprotein subfractions in patients
      with hyperlipidemia: A primary study.
AB  - OBJECTIVE: To investigate the effects of Hedan Tablet () on serum lipid profile,
      proprotein convertase subtilisin/kexin type 9 (PSCK9) and high-density
      lipoprotein (HDL) subfractions in patients with hyperlipidemia. METHODS: Thirty
      seven patients with hyperlipidemia were randomized to treatment with Hedan Tablet
      4.38 g/day as Hedan group (18 cases) or placebo (19 cases) as control group for 8
      weeks. The lipid profile, PCSK9 and HDL subfractions were determined at day 0 and
      week 8 in both groups respectively. RESULTS: Hedan treatment for 8 weeks mildly
      decreased serum low-density lipoprotein cholesterol (LDL-C) levels, while no
      changes were found in total cholesterol (TC), triglycerides (TG) and PCSK9
      concentrations. Furthermore, Hedan treatment increased the concentration of large
      high-density lipoprotein cholesterol (HDL-C) and the percentage of large HDL
      subfraction, while decreased the concentration of small HDL-C and the percentage
      of small HDL subfraction without changing serum HDL-C levels in patients with
      hyperlipidemia. CONCLUSION: Hedan treatment of 4.38 g per day for 8 weeks could
      confer a favorable effects on serum LDL-C concentration as well as HDL
      subfractions.

PMID- 25967609
TI  - Physico-chemical stress induced amyloid formation in insulin: Amyloid
      characterization, cytotoxicity analysis against human neuroblastoma cell lines
      and its prevention using black seeds (Nigella sativa).
AB  - OBJECTIVE: To investigate the aggregation and fibrillation of insulin at low pH
      and moderate temperature; and to further test the aggregated insulin for its
      cytotoxicity on human neuroblastoma (SH-SY5Y) cell line and inhibition of the
      cytotoxicity by black seeds (Nigella sativa) extract. METHODS: Bovine pancreatic
      insulin was incubated at pH 2.0, 45 C under stirring condition at 400 r/min for
      24 h. Amyloids like structures in the aggregated insulin were characterized using
      various techniques such as thioflavin T assay (ThT), 1-anilinonaphthalene-8
      sulfonic acid (ANS) fluorescence, circular dichroism (CD) and dynamic light
      scattering (DLS). Moreover, cytotoxicity of aggregated insulin was monitored on
      SH-SY5Y cell line in the presence and absence of black seeds extract using
      standard 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT),
      lactate dehydrogenase (LDH) and reactive oxygen species (ROS) assay kit. RESULTS:
      Our finding demonstrated that insulin under the mentioned conditions formed
      amyloid-like structure. ANS binding to aggregated insulin showed increase in
      fluorescence, suggesting structural change and increase in hydrophobicity in
      insulin occurring during the fibril formation. DLS measurement revealed
      progressive increase in hydrodynamic radius of aggregated insulin. Cytotoxicity
      assays illustrated aggregated insulin induced apoptosis in SH-SY5Y cell through
      ROS formation. Moreover, LDH measurement showed aggregated insulin triggered
      membrane damage in SH-SY5Y cell lines. Black seeds extract was found to inhibit
      amyloid formation and protected the cells against amyloid toxicity. CONCLUSION:
      Insulin molded into amyloid like structure at low pH and under stirring
      conditions. Characterization of insulin aggregates illustrated conformational
      change in insulin and it experiences alpha-helix to beta-sheet transition during
      the course of fibrillation. Black seeds extract inhibited amyloid progression of
      insulin via ROS scavenging and restrained the cytotoxicity caused by insulin
      fibrils suggesting black seeds containing polyphenols may serve as a lead
      structure to a novel anti-amyloidogenic drugs.

PMID- 25967610
TI  - Hyperspectral quantitative imaging of gas sources in the mid-infrared.
AB  - An imaging Fourier transform spectrometer operating in the medium infrared (1800
      5000  cm(-1)) has been used to image two gas sources: a controlled CO2 leak at
      room temperature and the exhaust of a combustion engine. Spectra have been
      acquired at a resolution of 0.5  cm(-1) using an extended blackbody as the
      background. By fitting them with theoretical spectra generated with parameters
      from the High-Resolution Transmission Molecular Absorption database, quantitative
      maps of temperature and gas column density (concentration.path product) for the
      gas plumes have been obtained. Spectra are related to gas plume parameters by
      means of a radiometric model that takes into account not only gas absorption, but
      also its emission and the atmospheric absorption, as well as the instrument
      lineshape function. Measurements for the gas leak show very good agreement
      between retrieved and nominal values of temperature and CO2 column density. This
      result has direct application to obtain quantitative imaging of exhaust emissions
      from automobiles and other mobile sources, as shown here with measurements of
      exhaust gases in a diesel engine.

PMID- 25967608
TI  - Chinese tuina downregulates the elevated levels of tissue plasminogen activator
      in sciatic nerve injured Sprague-Dawley rats.
AB  - OBJECTIVE: To elucidate the mechanism of Chinese tuina in treating sciatic nerve
      crush injury, and to detect the levels of tissue plasminogen activator (tPA) and
      plasminogen activator inhibitor-1 (PAI-1), which is thought to play an important
      role in nerve regeneration. METHODS: Thirty-two adult male Sprague-Dawley rats
      were subjected to sciatic nerve crush injury and 16 rats (sham-operated group)
      went through a sham operation. Control group was given no treatment while tuina
      group received tuina therapy since day 7 post-surgery. Tuina treatment was
      performed once a day and lasted for 20 days. The sciatic functional index was
      examined every 5 days during the treatment session. The rats' gastrocnemius
      muscles were evaluated for changes in mass and immunohistochemistry techniques
      were performed to detect the levels of tPA and PAI-1. RESULTS: Tuina therapy
      improved the motor function of sciatic nerve injured rats (P<0.05), however, it
      did not increase muscle volume (P<0.05). Tuina downregulated the levels of tPA
      and PAI-1 (P<0.05). CONCLUSIONS: The present study implies that tuina treatment
      could accelerate rehabilitation of peripheral nerve injury.

PMID- 25967611
TI  - Comprehensive study on the light shielding potential of thermotropic layers for
      the development of new materials.
AB  - In recent years thermotropic overheating protection glazings have been the focus
      for both solar thermal collector technology and architecture. A thermotropic
      glazing changes its light transmittance from highly transparent to light
      diffusing upon reaching a certain threshold temperature autonomously and
      reversibly. In thermotropic systems with fixed domains (TSFD) the scattering
      domains are embedded in a polymer matrix, which exhibits a sudden change of the
      refractive index upon reaching a threshold temperature. The aim of the present
      study was to comprehensively investigate the light shielding characteristics and
      potential of TSFD materials by applying simulation of light scattering in
      particle-filled layers. In random walk simulations a variety of parameters were
      varied systematically, and the effect on the light transmission behavior of TSFD
      was studied. The calculation steps of the simulation process are shown in detail.
      The simulations demonstrate that there is great potential for the production of
      functional materials with high overheating protection efficiency. 

PMID- 25967612
TI  - Two-dimensional quantitative measurements of methyl radicals in methane/air
      flame.
AB  - Two-dimensional (2D) quantitative measurements of methyl (CH3) radicals in a
      methane/air Hencken flame at atmospheric pressure are performed using coherent
      microwave Rayleigh scattering (Radar) from Resonance Enhanced Multi-Photon
      Ionization (REMPI) technique. The 2D scanning and subsequent quantification are
      employed for Radar REMPI. The 2D quantitative results are used to verify the
      numerical calculations. The line-integral effect was involved in the calculation
      due to the real experimental configuration. A 25% difference existed between the
      experimental results and numerical calculation, while the overall concentration
      distributions between experiment and modeling of single flamelet have fairly good
      agreement with each other.

PMID- 25967613
TI  - Design of optical systems for LED road luminaires.
AB  - The introduction of light-emitting diodes (LEDs) for lighting necessitated a
      completely new quality in the construction of luminaires. The different
      production technology required new methods and designing tools. It also
      challenged designers with new problems to solve. This paper presents the design
      process of a LED luminaire from concept to implementation, exemplified by road
      lighting, and describes the methods and procedures used by the designer. Also,
      technological problems influencing the quality of the above lighting are
      addressed. 

PMID- 25967614
TI  - Review of multiscale optical design.
AB  - Multiscale optical design is an approach that has been successfully utilized for
      over 100 years by optical designers and engineers to overcome challenges and
      achieve desired optical system performance. The benefits of the design paradigm
      include improving light collection, creating specific symmetries that can be
      exploited, collecting additional information about the object space, partitioning
      the optical field to enable piecewise correction of aberrations, and alleviating
      packing constraints. The purpose of this paper is to review the historical
      emergence of the use of multiscale optical design and present key examples of
      developments that have expanded its capabilities over the years. 

PMID- 25967615
TI  - Linear and nonlinear light localization through scattering media.
AB  - We extend the principles of time-resolved super-resolution source localization
      from diffractive microscopy to the imaging of objects through scattering media.
      We show that isolation and localization of the scattering (versus diffractive)
      point-spread function can be done by individually illuminating or individually
      darkening image segments. We experimentally demonstrate reconstruction of both
      bright and dark sources. Further, we show that self-focusing nonlinearity
      improves the localization accuracy for bright sources. 

PMID- 25967616
TI  - Transverse mode instability induced by stimulated Brillouin scattering in a
      pulsed single-frequency large-core fiber amplifier.
AB  - We report the observation of transverse mode instability (TMI) in a pulsed single
      frequency ytterbium-doped large-core fiber amplifier in which stimulated
      Brillouin scattering (SBS) is generated easily owing to the high peak power and
      narrow linewidth of the laser pulses. It was shown experimentally that the
      threshold of TMI is almost the same as that of SBS and that the suppression of
      SBS also increases the threshold of TMI, which indicates that the TMI originates
      from SBS in the fiber. 

PMID- 25967617
TI  - Secure chaotic transmission of electrocardiography signals with acousto-optic
      modulation under profiled beam propagation.
AB  - Electrocardiography (ECG) signals are used for both medical purposes and
      identifying individuals. It is often necessary to encrypt this highly sensitive
      information before it is transmitted over any channel. A closed-loop acousto
      optic hybrid device acting as a chaotic modulator is applied to ECG signals to
      achieve this encryption. Recently improved modeling of this approach using
      profiled optical beams has shown it to be very sensitive to key parameters that
      characterize the encryption and decryption process, exhibiting its potential for
      secure transmission of analog and digital signals. Here the encryption and
      decryption is demonstrated for ECG signals, both analog and digital versions,
      illustrating strong encryption without significant distortion. Performance
      analysis pertinent to both analog and digital transmission of the ECG waveform is
      also carried out using output signal-to-noise, signal-to-distortion, and bit
      error-rate measures relative to the key parameters and presence of channel noise
      in the system. 

PMID- 25967618
TI  - Measurement method for optical retardation based on the phase difference effect
      of laser feedback fringes.
AB  - We present a measurement method for optical phase retardation, which utilizes a
      phase-difference phenomenon of the feedback fringes in orthogonally polarized
      directions of a laser with anisotropic weak feedback. This phase difference is
      dominated by the measured retardation. The measurement principles are given based
      on the 3-mirror cavity model, and experiments are conducted with quartz
      waveplates (WPs). A measurement range 0 degrees -180 degrees  is achieved, the
      uncertainty is theoretically better than 0.5 degrees , and the measurement
      precision can be improved further. This method does not require researchers to
      know beforehand the principal axes directions of the WPs, and has better anti
      disturbance ability than the previous method based on laser feedback. 

PMID- 25967619
TI  - Reducing the risk of laser damage in a focal plane array using linear pupil-plane
      phase elements.
AB  - A compact imaging system with reduced risk of damage owing to intense laser
      radiation is presented. We find that a pupil phase element may reduce the peak
      image plane irradiance from an undesirable laser source by two orders of
      magnitude, thereby protecting the detector from damage. The desired scene is
      reconstructed in postprocessing. The general image quality equation (GIQE) [Appl.
      Opt.36, 8322 (1997)] is used to estimate the interpretability of the resulting
      images. A localized loss of information caused by laser light is also described.
      This system may be advantageous over other radiation protection approaches
      because accurate pointing and nonlinear materials are not required.

PMID- 25967620
TI  - Nonlinear dynamics of double-pass cross-polarized wave generation in the
      saturation regime.
AB  - The conversion efficiency of cross-polarized wave (XPW) generation can be
      improved using two separate thinner nonlinear crystals versus a single thick one,
      due to the evolution of the beam sizes and individual phases after the first
      crystal. In this paper, we present an alternative scheme in which a curved mirror
      is used to reimage a plane just after the BaF2 crystal for a second pass. We also
      develop a simple analytic model for XPW conversion that describes the origin of a
      nonlinear phase mismatch and nonlinear lensing for both the fundamental wave and
      XPW. Coupled with the numerical solution for the process and the Fresnel
      propagation after the first pass, we also explore the factors that affect the
      efficiency of saturated, seeded XPW conversion. These include the development of
      the on-axis relative phase difference in the first crystal and after it (during
      free-space propagation), mode matching, wavefront curvature difference, and
      crystal tuning angle. We also experimentally demonstrate that the beam quality of
      the XPW signal after the second pass can be improved by the reimaging.

PMID- 25967621
TI  - Fiber-optic differential absorption sensor for accurately monitoring biomass in a
      photobioreactor.
AB  - A fiber-optic differential absorption sensor was developed to accurately monitor
      biomass growth in a photobioreactor. The prepared sensor consists of two probes:
      the sensor and the reference. The sensor probe was employed to monitor the
      biomass and changes in the liquid-phase concentration in a culture. To separate
      the liquids from photosynthetic bacteria CQK 01 and measure the liquid-phase
      concentration, a proposed polyimide-silica hybrid membrane was coated on the
      sensing region of the reference probe. A linear relationship was observed between
      the sensor output signal and the biomass from the lag phase to the decline phase.

PMID- 25967622
TI  - On-orbit characterization of the VIIRS solar diffuser and solar diffuser screen.
AB  - We analyze bidirectional reflectance factors (BRF) of the solar diffuser (SD) and
      vignetting function (VF) of the SD screen (SDS) for on-board calibration of the
      visible infrared imaging radiometer suite (VIIRS). Specific focus is placed on
      the products of the BRF and VF, which are the main inputs for calibration of the
      SD and its accompanying solar diffuser stability monitor (SDSM), which tracks SD
      degradation. A set of 14 spacecraft yaw maneuvers for the Suomi National Polar
      Orbiting Partnership satellite, which houses the VIIRS instrument, was carefully
      planned and carried out over many orbits to provide the necessary information on
      the dependence of VIIRS instrument response on solar angles. Along with the
      prelaunch measurements for the SDS VF and SD BRF, the absolute form of the BRF-VF
      product is determined for each of the reflective solar bands (RSB) and the SDSM
      detectors. Consequently, the absolute form of the SDS VF also is obtained from
      the RSB and SDSM detectors using the yaw maneuver data. The results show that the
      BRF-VF product for an RSB is independent of the detector, gain status, and half
      angle mirror side. The derived VFs from the RSB and the SDSM detectors also show
      reasonable agreement with each other, as well as with the prelaunch VF
      measurements, and further demonstrate only geometrical dependence, which, in this
      work, is characterized by solar angles. The derived calibration coefficients,
      called the F-factors, from the application of the derived functions in this study
      show a significantly improved pattern. A small band-dependent residual seasonal
      fluctuation on the level of ~0.2%-0.4% remains in the F-factors for each RSB and
      is further improved by a corrective function with linear dependence on the solar
      azimuth angle in the nominal attitude instrument coordinate system to the VF. For
      satellite ocean color remote sensing, on-orbit instrument calibration and
      characterization are particularly important for producing accurate and consistent
      ocean color products. The result of this work has the most significant and direct
      impact on ocean color products. 

PMID- 25967623
TI  - Optical properties of zirconium carbide in 60-200 A wavelength region using x-ray
      reflectivity technique.
AB  - Optical constants of zirconium carbide (ZrC) have been determined in the soft x
      ray region of 60-200 A wavelength using angle-dependent x-ray reflectivity
      measurements. Reflectivity measurements are carried out at the reflectivity
      beamline of the Indus-1 synchrotron radiation source. Derived optical constants
      (delta and beta) are compared with the tabulated values [At. Data Nucl. Data
      Tables 54, 181 (1993)]. The optical constants are 15%-35% lower than bulk values
      in the 60-200 A wavelength region. Near the Zr M4 edge 187 eV (66.3 A), the delta
      values were close to bulk values with a deviation of 5%-10%. A large deviation of
      ~20% was found in beta values especially near the Zr M4 edge region, whereas it
      was in close agreement in the wavelength range away from the edge. To the best of
      our knowledge, this paper gives the first reported experimental values of optical
      constants for zirconium carbide in the 60-200 A wavelength region.

PMID- 25967624
TI  - Polarimetric characterization of birefringent filter components.
AB  - Over the past 75 years, birefringent filter technology has evolved significantly.
      For nearly that same period of time, these filters have been designed and used by
      solar scientists to study the Sun. Prior to assembling these types of filters,
      each component, e.g., polarizers and wave plates, is characterized to determine
      its polarimetric parameters to ensure the desired filter design performance. With
      time and cost becoming an ever increasing issue, it is imperative to test
      components designated for a birefringent filter efficiently. This article
      addresses a shift to increased efficiency when testing components of very low
      volume (<5 units) solar research filters that minimizes high-priced hardware
      expenditures, i.e., Mueller matrix spectropolarimeter. 

PMID- 25967625
TI  - Further investigation on the phase stitching and system errors in digital
      holography.
AB  - In this work, an improved phase stitching algorithm is proposed in digital
      holography (DH) based on a deduced phase errors model and a global optimization
      algorithm. In addition, to correct the relative rotation error between the
      coordinate systems of a CCD and xy-motion stages, we presented a simple and
      reliable image-based correction method. The experimental results obtained from
      our proposed method are compared with those calculated from the existing phase
      stitching method to verify the performance of the presented method. It is shown
      that our new proposed methods are robust and valid for measurement of a large
      microstructure element. As far as we know, the improved phase stitching algorithm
      and image-base correction method have not been discussed in DH, as we presented
      in this paper. 

PMID- 25967626
TI  - Packaged microsphere-taper coupling system with a high Q factor.
AB  - A novel packaged microsphere-taper coupling system which consists of a glass tube
      and two glass plates is proposed and demonstrated in this paper. We analyze the
      impact of the microsphere distortion on the resonant spectrum and it is observed
      that a very high quality factor (Q) up to 1.08*10(8) can be achieved by
      optimizing the microsphere position and orientation relative to the fiber taper.
      The maintenance of Q and a stable spectrum are realized by placing the packaged
      structure in a sealed organic glass box. Furthermore, to verify the
      practicability of the sealed device, thermal sensing experiments are carried out,
      which indicates the excellent convenience of the device with a resolution of
      1.12*10(-4) degrees C. The portability and robustness of the packaged structure
      make it strikingly attractive and illustrate its potential in practical
      microcavity sensors and lasers.

PMID- 25967627
TI  - Intermodal interferometer with low insertion loss and high extinction ratio
      composed of a slight offset point and a matching long period grating in two-mode
      photonic crystal fiber.
AB  - An all-fiber modal interferometer based on a long period grating (LPG) inscribed
      in a two-mode photonic crystal fiber (PCF) and a slight core-offset spliced end
      is proposed and demonstrated. The LPG is fabricated to realize energy coupling
      from LP01 core mode to LP11 core mode, and the two core modes will interfere at
      the slight core-offset spliced end. We analyze the impact of energy coupling
      efficiencies of the LPG and the output spliced end on the extinction ratio of the
      interference fringes. With an appropriate energy coupling efficiency matching
      condition, our modal interferometer can realize lower insertion loss and high
      extinction ratio. Moreover, the sensitivities of our interferometer to strain and
      temperature are investigated, and the good stability of this device to external
      refractive index change is also demonstrated. As an all-fiber interferometer made
      of pure silica, this device has great potential applications in high temperature
      sensing fields, especially in harsh conditions.

PMID- 25967628
TI  - Influence and control of spherical aberration in polishing off-axis aspherical
      mirrors by the stressed method.
AB  - The redundant spherical aberration of deformation can be caused by the weight of
      the stressed mirror polishing (SMP) apparatus in the continuous polishing (CP)
      process, and the elastic model to correct the spherical aberration by exerting
      center lateral loading is proposed. Subsequently, the analytic solution of mirror
      deformation is given by using a piecewise method. Next, the variation trend of
      mirror deformation with the loading force and the loading area size by the center
      lateral loading method is discussed. Following corresponding simulation
      calculation is carried out using finite element analysis (FEA) software. And the
      FEA result is compared with analytical solution. The experiment for the edge
      loading force case is accomplished. Furthermore, a comparison between theoretical
      calculation and experiment results is provided. All of these verify the validity
      of the theoretical model and the analytic solution. Finally, we introduce another
      method called the bending mirror technique for correcting additional spherical
      aberration of mirror deformation, calculating and acquiring the optimum inner
      radius for bending and the corresponding surface residual error. 

PMID- 25967629
TI  - Numerical and theoretical analysis on the absorption properties of metasurface
      based terahertz absorbers with different thicknesses.
AB  - In this paper, we numerically and theoretically discuss the novel absorption
      properties of a conventional metasurface-based terahertz (THz) electromagnetic
      (EM) absorber with different dielectric thicknesses. Two absorption modes are
      presented in the considered frequency band due to the increased dielectric
      thickness, and both modes can achieve near-unity absorptions when the dielectric
      layers reach additional nlambda(d)/2 (n=1, 2) thicknesses, where lambda(d) is the
      operating wavelength at the peak absorption in the dielectric slabs. The surface
      currents between the metasurface resonators and ground plane are not associated
      any longer, different from the conventional thin absorbers. Moreover, the EM wave
      energies are completely absorbed by the metasurface resonators and dielectric
      layer, and the main function of ground plane is to reflect the incident EM waves
      back to the resonators. The discussed novel absorption properties are analyzed
      and explained by classical EM theory and interference theory after numerical
      demonstrations. These findings can broaden the potential applications of the
      metasurface-based absorbers in the THz frequency range for different
      requirements.

PMID- 25967630
TI  - Analytic known-plaintext attack on a phase-shifting interferometry-based
      cryptosystem.
AB  - We demonstrate a new analytic approach to a known-plaintext attack (KPA) on an
      optical cryptosystem based on the phase-shifting interferometry (PSI) technique.
      With the proposed analytic attack method, an opponent can access the exact
      decryption keys and obtain perfect attack results. This demonstration, to the
      best of our knowledge, shows for the first time that the optical cryptosystem
      based on the PSI technique is vulnerable to KPA. 

PMID- 25967631
TI  - Effect of injection current and temperature on signal strength in a laser diode
      optical feedback interferometer.
AB  - We present a simple analytical model that describes the injection current and
      temperature dependence of optical feedback interferometry signal strength for a
      single-mode laser diode. The model is derived from the Lang and Kobayashi rate
      equations, and is developed both for signals acquired from the monitoring
      photodiode (proportional to the variations in optical power) and for those
      obtained by amplification of the corresponding variations in laser voltage. The
      model shows that both the photodiode and the voltage signal strengths are
      dependent on the laser slope efficiency, which itself is a function of the
      injection current and the temperature. Moreover, the model predicts that the
      photodiode and voltage signal strengths depend differently on injection current
      and temperature. This important model prediction was proven experimentally for a
      near-infrared distributed feedback laser by measuring both types of signals over
      a wide range of injection currents and temperatures. Therefore, this simple model
      provides important insight into the radically different biasing strategies
      required to achieve optimal sensor sensitivity for both interferometric signal
      acquisition schemes. 

PMID- 25967632
TI  - V-groove all-fiber core-cladding intermodal interferometer for high-temperature
      sensing.
AB  - Novel V-groove all-fiber core-cladding intermodal interferometers fabricated by
      CO2 laser irradiation on a standard single-mode fiber are described. The high
      order cladding modes are excited due to the special V-groove structure. The
      interferometers are classified as Mach-Zehnder and Michelson type based on the
      way they are structured. Benefiting from the large difference of thermal
      coefficients of the core and high-order cladding modes, both types receive high
      temperature sensitivity by monitoring the wavelength shift of the interference
      spectrum, and their responses to temperature are similar. Compared with the Mach
      Zehnder interferometer, the Michelson interferometer is more compact and more
      flexible in application.

PMID- 25967633
TI  - Blackening of metals using femtosecond fiber laser.
AB  - This study presents an unprecedented high throughput processing for super
      blackening and superhydrophobic/hydrophilic surface on both planar and nonplanar
      metals surfaces. By using a high pulse repetition rate femtosecond (fs) fiber
      laser, a light trapping microstructure and nanostructure is generated to absorb
      light from UV, visible to long-wave infrared spectral region. Different types of
      surface structures are produced with varying laser scanning conditions (scanning
      speed and pitch). The modified surface morphologies are characterized using
      scanning electron microscope and the blackening effect is investigated through
      spectral measurements. Spectral measurements show that the reflectance of the
      processed materials decreases sharply in a wide wavelength range and the decrease
      occurs at different rates for different scanning pitches and speeds. Above 98%
      absorption over the entire visible wavelength region and above 95% absorption
      over the near-infrared, middle-wave infrared and long-wave infrared regions range
      has been demonstrated for the surface structures, and the absorption for specific
      wavelengths can go above 99%. Furthermore, the processing efficiency of this fs
      fiber laser blackening technique is 1 order of magnitude higher than that of
      solid-state fs laser and 4 times higher than that of picosecond (ps) laser.
      Further increasing of the throughput is expected by using higher repetition and
      higher scanning speed. This technology offers the great potential in applications
      such as constructing sensitive detectors and sensors, solar energy absorber, and
      biomedicine. 

PMID- 25967634
TI  - Diffuse reflecting material for integrating cavity spectroscopy, including ring
      down spectroscopy.
AB  - We report the development of a diffuse reflecting material with measured
      reflectivity values as high as 0.99919 at 532 nm and 0.99686 at 266 nm. This
      material is a high-purity fumed silica, or quartz powder, with particle sizes on
      the order of 40 nm. We demonstrate that this material can be used to produce
      surfaces with nearly Lambertian behavior, which in turn can be used to form the
      inner walls of high-reflectivity integrating cavities. Light reflecting off such
      a surface penetrates into the material. This means there will be an effective
      "wall time" for each reflection off the walls in an integrating cavity. We
      measure this wall time and show that it can be on the order of several
      picoseconds. Finally, we introduce a technique for absorption spectroscopy in an
      integrating cavity based on cavity ring-down spectroscopy. We call this technique
      integrating cavity ring-down spectroscopy.

PMID- 25967635
TI  - Treating Atherosclerotic Disease: A Still-Unsolved Challenge.

PMID- 25967636
TI  - Effect of sealing infected dentin with glass ionomer cement on the abundance and
      localization of MMP-2, MMP-8, and MMP-9 in young permanent molars in vivo.
AB  - BACKGROUND: The study of MMPs' behavior in carious lesions contributes to the
      understanding of the mechanisms involved in dentin reorganization after
      restoration. AIM: To compare the abundance and localization of MMPs 2, 8, and 9
      in infected dentin before and after restoration. DESIGN: The sample consisted of
      23 young permanent molars with active deep carious lesions. Infected carious
      dentin samples were collected from the same tooth at baseline and 60 days after
      cavity lining with GIC and composite resin restoration and processed for
      immunohistochemistry assays. After digital images were obtained, two calibrated
      operators analyzed the samples according to the immunostaining intensity and the
      MMPs' localization. Chi-square test was used for statistical analysis. RESULTS:
      The intensity of immunostaining for MMP-8 was reduced after 60 days (P = 0.02),
      and no difference was observed for MMP-2 (P = 0.32) and MMP-9 (P = 0.14). The
      MMPs' distribution was generalized in the intertubular dentin and absent or
      located in the intratubular dentin, regardless of the period. CONCLUSION: The
      sealing of infected carious dentin in young permanent molars reduced the
      expression of MMP-8, which is consistent with the initial remodeling process of
      the dentin matrix.

PMID- 25967637
TI  - Effect of lipid peroxidation, antioxidants, macro minerals and trace elements on
      eczema.
AB  - The exact etiology and pathogenesis of eczema are not yet fully understood,
      although different factors are considered as pathogenic mechanisms in the
      development of eczema. Our study was designed to determine extent of serum lipid
      peroxidation, antioxidants, macro minerals and trace elements in patients with
      eczema, and thereby, find any pathophysiological correlation. The study was
      conducted as a case-control study with 65 eczema patients as cases and 65 normal
      healthy individuals as controls. Lipid peroxidation was assessed by measuring the
      serum level of malondialdehyde (MDA). Antioxidants- vitamin A and E concentration
      was determined by RP-HPLC method whereas vitamin C was evaluated for serum
      ascorbic acid by UV spectrophotometric method. Serum macro minerals (Na, K, Ca)
      and trace elements (Zn, Fe) were determined by Atomic Absorption Spectroscopy
      (AAS). This study found significantly higher level of MDA (p < 0.001) and lower
      level of antioxidants (p < 0.05) in patients in comparison to the control
      subjects. Analysis of serum macro minerals (Na, K and Ca) and trace elements (Zn,
      Fe) found that the mean values of Na, K, Ca, Zn and Fe were 2771.60 +/- 75.64,
      66.33 +/- 3.03, 48.41 +/- 2.50, 0.30 +/- 0.02 and 0.29 +/- 0.009 mg/L for the
      patient group and 3284.81 +/- 34.51, 162.18 +/- 3.72, 87.66 +/- 2.10, 0.75 +/-
      0.06 and 0.87 +/- 0.06 mg/L for the control group, accordingly. There was a
      significant difference for all the minerals between the patients and controls (p
      < 0.001). This study suggests a strong association between the pathogenesis of
      eczema with the elevated level of MDA and depleted level of antioxidants, macro
      minerals, and trace elements.

PMID- 25967638
TI  - Using Freire's Participatory Educational Method to Understand the Experience of
      Living With Chronic Illness in the Current Age of Globalization.
AB  - BACKGROUND: Many approaches and efforts have been used to better understand
      chronic diseases worldwide. Yet, little is known about the meaning of living with
      chronic illness under the pressures of globalization and neoliberal ideologies.
      Through Freire's participatory educational method, this article presents an
      innovative approach to understanding the multiple dimensions of living with
      chronic illness. In this way, we hope to use an innovative approach to address
      the impact of globalization on the daily life of chronically ill people and thus
      expand to the body of knowledge on nursing. PURPOSE: This article uses Freire's
      participatory educational method to understand the multiple dimensions of living
      with chronic illness. METHODS: This qualitative study follows an interpretive
      inquiry approach and uses a critical hermeneutic phenomenological method and
      critical research methodologies. Five participants were recruited for this
      participatory educational activity. Data collection methods included digitally
      recorded semistructured individual interviews and a Freire's participatory
      educational method session. Data analysis included a thematic analysis. RESULTS:
      Participants reported lacking adequate access to healthcare services because of
      insurance policies; a general perception that they were an unwanted burden on the
      healthcare system; and a general lack of government support, advocacy, and
      political interest. This research activity assisted participants to gain a new
      critical perspective about the condition of others with chronic diseases and thus
      provided an enlightening opportunity to learn about the illnesses and experiences
      of others and to realize that others experienced the same oppression from the
      healthcare system. Participants became agents of change within their own families
      and communities. CONCLUSIONS: Chronic diseases cause many economic and social
      consequences in their victims. These findings urge us to move from merely
      acknowledging the difficulties of people who live with chronic illness in an age
      of globalization to taking the actions necessary to bring about healthcare,
      social, and political reform through a process of conscientization and mutual
      transformation.

PMID- 25967639
TI  - Common factors associated with choking in psychiatric patients.
AB  - BACKGROUND: Choking is common among psychiatric patients and represents one of
      the main causes of death in this patient population. PURPOSE: We aimed to
      identify common factors associated with choking among psychiatric patients.
      METHODS: The demographic information and medical history of 250 psychiatric
      patients living in an acute psychiatric ward were retrieved from medical charts,
      interview records, and check lists. Coughing while eating and swallowing
      difficulties were assessed based on patient self-reports. The main outcomes were
      choking while taking drugs (CTD) as observed by nursing staffs and choking
      experiences during hospitalization (CEH) as reported by the patients. Chi-square
      tests were used to examine the potential associations among the independent
      variables. Multiple logistic regression was used to further examine those
      independent variables found to be significantly associated with CTD to estimate
      their relative contributions. RESULTS: CEH was reported in 50.8%, and CTD was
      observed in 17.6% of study participants. Use of anxiolytics, consuming a
      semiliquid or liquid diet, coughing while eating, and swallowing difficulties
      were found to be associated with CTD. Coughing while eating was the only
      independent variable associated with CEH. Further logistic regression on the
      relationships between CTD and variables including the use of anxiolytics,
      coughing while eating, and swallowing difficulties showed the independent
      contributions of these variables in the model. The odds ratios were 12.8 (p =
      .003), 16.7 (p < .001), and 21.7 (p = .001) for each of the three respective
      variables. CONCLUSION: The use of anxiolytics, coughing while eating, and
      swallowing difficulties all potentially contributed to the choking events in our
      sample. Additional precautions should thus be taken in caring for psychiatric
      patients who use anxiolytics, who have a history of coughing while eating, or who
      exhibit swallowing difficulties to prevent choking events.

PMID- 25967640
TI  - Relationships among communication competence, self-efficacy, and job satisfaction
      in Korean nurses working in the emergency medical center setting.
AB  - BACKGROUND: The communication competence of nurses working in emergency medical
      center settings is essential to establish a therapeutic nurse-patient
      relationship. Education and strategic development are required to improve the
      communication competence of emergency room (ER) nurses. PURPOSE: This study was
      conducted to determine the relationships among individual communication
      competence, self-efficacy, and job satisfaction in Korean nurses in the emergency
      medical center setting. METHODS: A cross-sectional descriptive design was
      adopted. The study sample included 214 nurses at 11 emergency medical centers in
      Seoul and Kyunggi-Do, Korea. Measures used included the Global Interpersonal
      Communication Competence, self-efficacy scale, and job satisfaction scale. The
      collected data were analyzed using the SPSS version 18.0 statistical software
      program and included descriptive statistics (frequency, percentage, mean,
      standard deviation, independent t test, analysis of variance, and Pearson's
      correlation coefficient). RESULTS: The degrees of communication competence and
      self-efficacy of ER nurses were good, with higher scores than the median values.
      However, the degree of job satisfaction was poor, indicating a lower score than
      the median value. Religious affiliation and previous participation in
      communication education each had a significant impact on communication
      competence. Religious affiliation and time of worse duty each had a significant
      impact on self-efficacy. Length of career (year) in the emergency medical center
      and type of hospital each had a significant impact on job satisfaction. Positive
      correlations were identified among communication competence, self-efficacy, and
      job satisfaction. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: This study supported the
      presence of significant correlations among communication competence, self
      efficacy, and job satisfaction. Thus, it is necessary to develop training
      programs that are customized to individual characteristics such as self-efficacy
      and job satisfaction to improve the communicative competence of ER nurses.

PMID- 25967641
TI  - First encounters with instructors: the experiences and perceptions of nursing
      students in Iran.
AB  - BACKGROUND: The first encounter between an instructor and his/her student
      influences the development of their mutual relationship. This phenomenon has
      received little attention in the literature within the context of nursing
      education. PURPOSE: This study explores and describes qualitatively the
      subjective experience and perceptions of nursing students related to their first
      encounter with instructors in both classroom and clinical settings. METHODS: A
      purposeful sampling method was utilized to select 15 nursing students from a
      nursing school in Iran to participate in semistructured interviews. Data were
      analyzed using a qualitative content analysis approach. RESULTS: Data analysis
      identified three main themes: (a) preexisting expectations, with the four
      subthemes of socially shared expectations, personal expectations, profession
      related expectations, and reputation-directed expectations; (b) student's
      judgment, with the three subthemes of assessing the instructor, assessing
      criteria, and good or bad beginning; and (c) future interactions, with the two
      subthemes of constructive decisions and destructive decisions.
      CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The results show that the initial student
      instructor encounter is a process in which students rely heavily on preexisting
      expectations to assess and judge the initial interaction with their instructor.
      The findings of this study may help nursing instructors in various national and
      cultural settings increase their awareness of the factors that influence their
      first encounters with students. Greater awareness may help positively shape
      student perspectives of the instructor's role and encourage students to
      collaborate with the instructor in the teaching and learning process in order to
      create a better outcome for both.

PMID- 25967642
TI  - Addressing disruption in family life: exploration of the perceived needs of the
      families of patients hospitalized in critical care units in Iran.
AB  - BACKGROUND: The stress faced by a family member impacts the whole family. Disease
      is a stressor that creates crises within families. PURPOSE: This study explores
      the perceived needs of the families of hospitalized patients in critical care
      units in the city of Arak, Iran. METHODS: This study used a qualitative design
      and a content analysis approach. After purposeful sampling, semistructured
      interviews were held with 16 participants. RESULTS: Using constant comparative
      analysis, one main theme and eight subthemes emerged from the data. The main
      theme was "addressing the disruption in family life." The subthemes were "not
      being fully informed," "not receiving empathy," "feeling insecure," "being
      mentally unstable," "being concerned about their patient's future," "being
      dissatisfied with the lack of facilities for the families of patients," "dealing
      with financial problems," and "having turbulence intrude on family life."
      CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The findings of this study underscore that
      it is important for medical teams to carefully identify and attend to the needs
      of the family caregivers of hospitalized patients to reduce the disruptive impact
      of hospitalization on family life.

PMID- 25967643
TI  - Gender differences? Internet use and parent-child communication about sex toward
      sexual attitudes among early adolescents in Taiwan.
AB  - BACKGROUND: With the progress of information technology, early adolescents are
      able to access sex-related information through the Internet easily. This
      information has been shown to have a significant influence on the sexual health
      of this population. In addition, parent-child communications about sex affect the
      sexual health of adolescents. Few empirical studies have focused on early
      adolescents and gender differences. PURPOSE: This study explores gender
      differences between early adolescents in terms of the use of the Internet to
      obtain sex-related information, parent-child communication, and sex-related
      knowledge and attitudes. METHODS: This cross-sectional and comparative study uses
      an analysis of covariance and a hierarchical regression for data analysis. The
      researchers recruited 457 sixth-grade boys (n = 204) and girls (n = 253) in
      southern Taiwan as participants and used a structured questionnaire to collect
      data. RESULTS: Participants exhibited significant differences in terms of
      Internet usage behavior, parent-child communications about sex, and sex-related
      knowledge and sexual attitudes. The male participants spent more time on
      "recreation and entertainment" activities on the Internet, whereas their female
      peers spent significantly more time searching for information. Regarding parent
      child communications about sex, girls had better mother-child communications than
      boys. In addition, no gender-based difference was found for father-child
      communications about sex. The knowledge of physical changes occurring during
      puberty and of menstrual healthcare among female participants was superior to
      their male counterparts. Girls had a more informed sexual attitude, particularly
      with regard to issues of gender roles, relationships with the opposite gender,
      and the social aspects of sex. Sex-related knowledge and parent-child
      communication about sex were the two major predictors of sexual attitudes for
      boys and girls, respectively. CONCLUSIONS: To develop healthy sexual attitudes
      among early adolescents, nursing professionals, families, and schools should
      enhance sex-related knowledge and parent-child communications, especially with
      boys. Early adolescence is a key time to provide sex education and Internet
      safety education to both boys and girls to improve their sexual health. This
      study may serve as a reference for families, schools, researchers, and
      policymakers for promoting the sexual health of early adolescents.

PMID- 25967644
TI  - Middle-aged female spouses of patients with metastatic cancer: lived experiences.
AB  - BACKGROUND: Although the survival rate for cancer is increasing because of
      advances in treatment technology, cancer still comes as a great shock to the
      families of patients who are in the advanced stages of this disease. When a
      married, middle-aged man is diagnosed with advanced cancer, his spouse most often
      becomes his primary caregiver. However, few studies have studied the lived
      experience of these middle-aged spouses. PURPOSE: This study explores the lived
      experience of middle-aged female spouses of husbands diagnosed with advanced
      cancer. METHODS: A qualitative design was used. In-depth interviews were
      conducted with participants whose spouses were being treated at the oncology
      outpatient department of a teaching hospital in northern Taiwan. The data were
      collected with purposive sampling over a 12-month period. RESULTS: A content
      analysis of 11 participant interviews revealed four themes: simultaneously
      bearing all layers of stress, changing of attitudes and values, developing the
      effective skills of caregiving, and gaining support from the family and from
      religion. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: A middle-aged female spouse
      faces many layers of stress and many crises in caring for her husband with
      advanced cancer. Female spouses in Taiwan tend to rely significantly more on
      internal resources (family) than external resources (friends and medical
      professionals). It is recommended that these families use external resources such
      as medical and social welfare systems more actively to facilitate their
      successful passage through these crises. Understanding the lived experiences of
      these female spouses helps nurses provide appropriate nursing interventions.

PMID- 25967645
TI  - The perspectives of Iranian patients with multiple sclerosis on continuity of
      care: a qualitative study.
AB  - BACKGROUND: Continuity in multiple sclerosis (MS) care has been cited as a
      critical feature of this care and necessary to improve medical outcomes. PURPOSE:
      This exploratory and descriptive research attempts to identify continuity of care
      from the experience and perspective of patients with MS at two teaching hospitals
      and the MS Society in Ahvaz, Iran. METHODS: In this study, 23 patients with MS
      were selected through purposeful sampling. Data were collected through in-depth
      and unstructured interviews and were analyzed using an inductive thematic
      analysis approach. RESULTS: Four main themes emerged from the analysis: human
      oriented attention, the necessity of purposeful planning, importance of
      responsibility, and caring with empathetic sensing. CONCLUSIONS/IMPLICATIONS FOR
      PRACTICE: Because of the importance of professional caring practice to continuity
      of care for patients with MS, we suggest that healthcare providers should include
      these aspects in care planning.

PMID- 25967646
TI  - Family caregivers' experiences of caring for patients with heart failure: a
      descriptive, exploratory qualitative study.
AB  - BACKGROUND: Living with heart failure is a complex situation for family
      caregivers. Many studies addressing the challenges faced by heart failure family
      caregivers have already been conducted in Western societal settings.
      Sociocultural factors and perspectives influence the family caring experience and
      roles. The ethnic/culturally based differences in family caring behavior make
      this a subject worth further exploration and clarification. PURPOSE: This study
      explores the experiences of family caregivers in Iran of caring for patients with
      heart failure. METHODS: A descriptive, exploratory, and qualitative approach was
      applied to gain authentic insight into the experiences of participants. Purposive
      sampling was used to recruit 21 family caregivers from three educational
      hospitals in Isfahan, Iran. Data were collected using semistructured interviews
      and field notes. Interviews and field notes were transcribed verbatim and
      concurrently analyzed. RESULTS: Three major themes emerged from the analysis of
      the transcripts: caregiver uncertainty, lack of familial and organizational
      support, and Allah-centered caring. Participants believed that they did not have
      the basic knowledge related to their disease and drugs. In addition, they
      received little guidance from the healthcare team. Lack of support and insurance
      as well as financial issues were major problems faced by the caregivers. They
      accepted the providence of Allah and noted that Allah always helps them
      accomplish their caregiving responsibilities. CONCLUSIONS/IMPLICATIONS FOR
      PRACTICE: The care performed by the caregivers of patients with heart failure
      exceeds their individual capabilities. Nurses, other healthcare providers, and
      health policy makers may use the findings of this study to develop more effective
      programs to address these challenges and to provide more effective
      support.Sociocultural factors and perspectives were the primary factors affecting
      the caregiving experiences of participants in this study. Improved understanding
      of these factors and perspectives will help healthcare providers develop and
      implement suitable intervention programs for caregivers. Healthcare professionals
      should develop context-based intervention programs to promote caregiver
      capabilities and encourage caregivers to participate to facilitate the caregiving
      roles of caregivers.

PMID- 25967647
TI  - Assessing the construct validity of the Chinese-Version Schizotypal Personality
      Questionnaire-Brief on male and female undergraduate students.
AB  - BACKGROUND: Screening for the schizotypal personality trait is one strategy to
      identify people who may be susceptible to early psychosis or be at high risk for
      prodromal psychosis. The Schizotypal Personality Questionnaire-Brief (SPQ-B) has
      been widely used to assess the schizotypal personality and has been translated
      into Chinese. However, the psychometric properties of the Chinese-version scale
      have yet to be evaluated. PURPOSE: This study evaluates the construct validity of
      the Chinese-version SPQ-B on a sample of male and female undergraduate students
      in Taiwan. METHODS: A cross-sectional design with convenient sampling was used
      for this study. The data were collected using the Chinese-version SPQ-B between
      October 2008 and June 2009. Participants included 513 male and 675 female
      undergraduate students in Taiwan. The factor construct validity of the scale was
      examined by confirmatory factor analysis using structural equation modeling with
      SPSS AMOS version 17 software. RESULTS: The results show that the three-factor
      model fits the data better than the one-factor model for both male and female
      participants. The male participants scored significantly higher than their female
      counterparts in terms of total scale, interpersonal subscales, and disorganized
      subscales. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The Chinese version of the SPQ
      B adequately achieves three-factor construct validity for undergraduate students.
      The scale may be used to screen for the schizotypal personality trait in both
      male and female college students to identify those at an elevated risk for mental
      illness.

PMID- 25967648
TI  - Central neural activation following contact sensitivity peripheral immune
      challenge: evidence of brain-immune regulation through C fibres.
AB  - This study tested the hypothesis that peripheral immune challenges will produce
      predictable activation patterns in the rat brain consistent with sympathetic
      excitation. As part of examining this hypothesis, this study asked whether
      central activation is dependent on capsaicin-sensitive C-fibres. We induced skin
      contact sensitivity immune responses with 2,4-dinitrochlorobenzene (DNCB), in the
      presence or absence of the acute C-fibre toxin capsaicin (8-methyl-N-vanillyl-6
      nonenamide) to trigger immune responses with and without diminished activity of C
      fibres. Innovative blood-oxygen-level-dependent functional magnetic resonance
      imaging data revealed that the skin contact sensitivity immune responses induced
      with DNCB were associated with localized increases in brain neuronal activity in
      treated rats. This response was diminished by pre-treatment with capsaicin 1 week
      before scans. In the same animals, we found expression of the immediate early
      gene c-Fos in sub-regions of the amygdala and hypothalamic sympathetic brain
      nuclei. Significant increases in c-Fos expression were found in the supraoptic
      nucleus, central amygdala and medial habenula following immune challenges. Our
      results support the idea that selective brain regions, some of which are
      associated with sympathetic function, process or modulate immune function through
      pathways that are partially dependent on C-fibres. Together with previous studies
      demonstrating the motor control pathways from brain to immune targets, these
      findings indicate a central neuroimmune system to monitor host status and
      coordinate appropriate host responses. 

PMID- 25967650
TI  - Multimodal Analgesic Protocol and Postanesthesia Respiratory Depression During
      Phase I Recovery After Total Joint Arthroplasty.
AB  - BACKGROUND: Multimodal analgesia protocols have shortened hospitalizations after
      total joint arthroplasty. It is unclear whether individual components of these
      protocols are associated with respiratory depression during phase I
      postanesthesia recovery. OBJECTIVES: To test the hypothesis that sedating
      analgesics used in a multimodal protocol are associated with an increased rate of
      phase I postanesthesia respiratory depression. METHODS: Our Department of
      Anesthesiology records were searched to identify patients undergoing total joint
      arthroplasty with a multimodal analgesia protocol, including peripheral nerve
      blockade, from 2008 through 2012. Patient records were reviewed for episodes of
      postanesthesia respiratory depression, and potential causative factors were
      abstracted and analyzed for potential associations. Respiratory depression was
      defined as apnea, hypopnea, oxyhemoglobin desaturations, or episodes of severe
      pain despite moderate to profound sedation. RESULTS: Of 11,970 patients who
      underwent joint arthroplasty, 2836 (23.7%; 237 per 1000 cases; 95% confidence
      interval [95% CI], 214-262) had episodes of respiratory depression. A higher rate
      of respiratory depression was observed among patients who underwent general
      anesthesia (312 per 1000 cases; 95% CI, 301-323) than neuraxial anesthesia (144
      per 1000 cases; 95% CI, 135-153) (P < 0.001). With both anesthetic techniques,
      respiratory depression was associated with preoperative use of gabapentin (>300
      mg) (P < 0.001 for both anesthesia groups) and sustained-release oxycodone (>10
      mg) (P = 0.01 for general anesthesia; P = 0.008 for neuraxial anesthesia).
      CONCLUSIONS: Use of medications with long-acting sedative potential was
      associated with increased risk of respiratory depression during phase I
      anesthesia recovery. These effects were more pronounced when used in conjunction
      with general anesthesia than with neuraxial anesthesia.

PMID- 25967649
TI  - Phase II Study of Oral Tegafur/Uracil and Leucovorin plus Bevacizumab as a First
      Line Therapy for Elderly Patients with Advanced or Metastatic Colorectal Cancer.
AB  - BACKGROUND/OBJECTIVE: Oral tegafur/uracil and leucovorin (UFT/LV) therapy is
      effective and safe for elderly patients with advanced or metastatic colorectal
      cancer (CRC). However, there are few studies on the combination of bevacizumab
      with UFT/LV. This clinical study evaluated the efficacy and safety of UFT/LV plus
      bevacizumab as a first-line therapy for elderly patients with advanced or
      metastatic CRC. METHODS: Forty patients with advanced or metastatic CRC aged >=
      75 years were enrolled in this multicenter, open-label, single-arm phase II
      study. All patients received oral UFT (300-600 mg) and LV (50 mg) twice daily on
      days 1-21 and intravenous bevacizumab (5 mg/kg) on days 1 and 15 of a 4-week
      cycle (University Hospital Medical Information Network No. UMIN000003447).
      RESULTS: The median follow-up period was 14.7 months. The response rate was 20.0%
      [95% confidence interval (CI): 9.1-35.6], median progression-free survival was
      8.9 months (95% CI: 5.3-11), and median overall survival was 21.7 months (95% CI:
      13.7-23.4). The only grade 3 hematological toxicity was neutropenia (3.0%), and
      the incidence rates of grade 3 nonhematological toxicity were low at <= 10%.
      CONCLUSION: UFT/LV plus bevacizumab is a promising first-line regimen for elderly
      patients with advanced or metastatic CRC. The combination is well tolerated and
      efficacious.

PMID- 25967651
TI  - Mechanism and site of inhibition of AMPA receptors: substitution of one and two
      methyl groups at the 4-aminophenyl ring of 2,3-benzodiazepine and implications in
      the "E" site.
AB  - 2,3-Benzodiazepines are a well-known group of compounds for their potential
      antagonism against AMPA receptors. It has been previously reported that the
      inhibitory effect of 2,3-benzodiazepine derivatives with a 7,8-ethylenedioxy
      moiety can be enhanced by simply adding a chlorine atom at position 3 of the 4
      aminophenyl ring. Here we report that adding a methyl group at position 3 on the
      4-aminophenyl ring, termed as BDZ-11-7, can similarly enhance the inhibitory
      activity, as compared with the unsubstituted one or BDZ-11-2. Our kinetic studies
      have shown that BDZ-11-7 is a noncompetitive antagonist of GluA2Q homomeric
      receptors and prefers to inhibit the closed-channel state. However, adding
      another methyl group at position 5 on the 4-aminophenyl ring, termed as BDZ-11-6,
      fails to yield extra inhibition on GluA2Q receptors. Instead, BDZ-11-6 exhibits a
      diminished inhibition of GluA2Q. Site interaction test indicates the two
      compounds, BDZ-11-6 and BDZ-11-7, bind to the same site on GluA2Q, which is also
      the binding site for their prototype, BDZ-11-2. Based on the results from this
      and our earlier studies, we propose that the binding site that accommodates the 4
      aminophenyl ring must contain two interactive points, with one preferring polar
      groups like chlorine and the other preferring nonpolar groups such as a methyl
      group. Either adding a chlorine or a methyl group may enhance the inhibitory
      activity of 2,3-benzodiazepine derivatives with a 7,8-ethylenedioxy moiety.
      Adding any two of the same group on positions 3 and 5 of the 4-aminophenyl ring,
      however, significantly reduces the interaction between these 2,3-benzodiazepines
      and their binding site, because one group is always repelled by one interactive
      point. We predict therefore that adding a chlorine atom at position 3 and a
      methyl group at position 5 of the 4-aminophenyl ring of 2,3-benzodiazepine
      derivatives with a 7,8-ethylenedioxy moiety may produce a new compound that is
      more potent. 

PMID- 25967652
TI  - Cloning, molecular modeling, and docking analysis of alkali-thermostable beta
      mannanase from Bacillus nealsonii PN-11.
AB  - An alkali-thermostable beta-mannanase gene from Bacillus nealsonii PN-11 was
      cloned by functional screening of E. coli cells transformed with pSMART/HaeIII
      genomic library. The ORF encoding mannanase consisted of 1100 bp, corresponding
      to protein of 369 amino acids and has a catalytic domain belonging to glycoside
      hydrolase family 5. Cloned mannanase was smaller in size than the native
      mannanase by 10 kDa. This change in molecular mass could be because of difference
      in the glycosylation. The tertiary structure of the beta-mannanase (MANPN11) was
      designed and it showed a classical (alpha/beta) TIM-like barrel motif. Active
      site of MANPN11 was represented by 8 amino acid residues viz., Glu152, Trp189,
      His217, Tyr219, Glu247, Trp276, Trp285, and Tyr287. Model surface charge of
      MANPN11 predicted that surface near active site was mostly negative, and the
      opposite side was positive which might be responsible for the stability of the
      enzymes at high pH. Stability of MANPN11 at alkaline pH was further supported by
      the formation of a hydrophobic pocket near active site of the enzyme. To
      understand the ability of MANPN11 to bind with different substrates, docking
      studies were performed and found that mannopentose fitted properly into active
      site and form stable enzyme substrate complex.

PMID- 25967653
TI  - Effects of aeration strategy on the evolution of dissolved organic matter (DOM)
      and microbial community structure during sludge bio-drying.
AB  - Sludge bio-drying in which sludge is dried by means of the heat generated by the
      aerobic degradation of its own organic substances has been widely used for sludge
      treatment. A better understanding of the evolution of dissolved organic matter
      (DOM) and its degradation drivers during sludge bio-drying could facilitate its
      control. Aeration is one of the key factors that affect sludge bio-drying
      performance. In this study, two aeration strategies (pile I-the optimized and
      pile II-the current) were established to investigate their impacts on the
      evolution of DOM and the microbial community in a full-scale sludge bio-drying
      plant. A higher pile temperature in pile I caused pile I to enter the DOM and
      microbiology stable stage approximately2 days earlier than pile II. The
      degradation of easily degradable components in the DOM primarily occurred in the
      thermophilic phase; after that degradation, the DOM components changed a little.
      Along with the evolution of the DOM, its main degradation driver, the microbial
      community, changed considerably. Phyla Firmicutes and Proteobacteria were
      dominant in the thermophilic stage, and genus Ureibacillus, which was the primary
      thermophilic bacteria, was closely associated with the degradation of the DOM. In
      the mesophilic stage, the microbial community changed significantly at first and
      subsequently stabilized, and the genus Parapedobacter, which belongs to
      Bacteriodetes, became dominant. This study elucidates the interplay between the
      DOM and microbial community during sludge bio-drying.

PMID- 25967654
TI  - Receptor for the F4 fimbriae of enterotoxigenic Escherichia coli (ETEC).
AB  - Infection with F4(+) enterotoxigenic Escherichia coli (ETEC) responsible for
      diarrhea in neonatal and post-weaned piglets leads to great economic losses in
      the swine industry. These pathogenic bacteria express either of three fimbrial
      variants F4ab, F4ac, and F4ad, which have long been known for their importance in
      host infection and initiating protective immune responses. The initial step in
      infection for the bacterium is to adhere to host enterocytes through fimbriae
      mediated recognition of receptors on the host cell surface. A number of receptors
      for ETEC F4 have now been described and characterized, but their functions are
      still poorly understood. The current review summarizes the latest research
      addressing the characteristics of F4 fimbriae receptors and the interactions of
      F4 fimbriae and their receptors on host cells. These include observations that as
      follows: (1) FaeG mediates the binding activities of F4 and is an essential
      component of the F4 fimbriae, (2) the F4 fimbrial receptor gene is located in a
      region of chromosome 13, (3) the biochemical properties of F4 fimbrial receptors
      that form the binding site of the bacterium are now recognized, and (4) specific
      receptors confer susceptibility/resistance to ETEC F4 infection in pigs.
      Characterizing the host-pathogen interaction will be crucial to understand the
      pathogenicity of the bacteria, provide insights into receptor activation of the
      innate immune system, and develop therapeutic strategies to prevent this illness.

PMID- 25967655
TI  - Methane biofiltration using autoclaved aerated concrete as the carrier material.
AB  - The methane removal capacity of mixed methane-oxidizing bacteria (MOB) culture in
      a biofilter setup using autoclaved aerated concrete (AAC) as a highly porous
      carrier material was tested. Batch experiment was performed to optimize MOB
      immobilization on AAC specimens where optimum methane removal was obtained when
      calcium chloride was not added during bacterial inoculation step and 10-mm-thick
      AAC specimens were used. The immobilized MOB could remove methane at low
      concentration (~1000 ppmv) in a biofilter setup for 127 days at average removal
      efficiency (RE) of 28.7 %. Unlike a plug flow reactor, increasing the total
      volume of the filter by adding a biofilter in series did not result in higher
      total RE. MOB also exhibited a higher abundance at the bottom of the filter, in
      proximity with the methane gas inlet where a high methane concentration was
      found. Overall, an efficient methane biofilter performance could be obtained
      using AAC as the carrier material.

PMID- 25967656
TI  - Generation and characterization of a protective mouse monoclonal antibody against
      human enterovirus 71.
AB  - Human enterovirus 71 (EV71) infection has emerged as a major threat to children;
      however, no effective antiviral treatment or vaccine is currently available.
      Antibody-based treatment shows promises to control this growing public health
      problem of EV71 infection, and a few potent monoclonal antibodies (mAbs)
      targeting viral capsid protein have been well described. Here, we generated an
      EV71-specific mouse mAb 2G8 that conferred full protection against lethal EV71
      challenge in a suckling mouse model. 2G8 belonged to IgM isotype and neutralized
      EV71 at the attachment stage. Biochemical assays mapped the binding epitope of
      2G8 to the SP70 peptide, which spanning amino acid residues 208-222 on the VP1
      protein. Alanine scanning mutagenesis defined the essential roles of multiple
      residues, including Y208, T210, G212, K215, K218, L220, E221, and Y222, for 2G8
      binding. Then, a panel of single mutation was individually introduced into the
      EV71 infectious clone by reverse genetics, and three mutant viruses, K215A,
      K218A, and L220A, were successfully recovered and characterized. Biochemical and
      neutralization assays revealed that K218A mutant partially escaped 2G8
      neutralization, while L220A completely abolished 2G8 binding and neutralization.
      In particular, neutralization assays with human sera demonstrated that K218A and
      L220A substitutions are also critical for antibody neutralization in natural
      infection population. These findings not only generate a protective mAb candidate
      with therapeutic potential but also provide insights into antibody-mediated EV71
      neutralization mechanism. 

PMID- 25967657
TI  - Fate of the insecticidal Cry1Ab protein of GM crops in two agricultural soils as
      revealed by 14C-tracer studies.
AB  - Insecticidal delta-endotoxins of Bacillus thuringiensis are among the most
      abundant recombinant proteins released by genetically modified (GM) crops into
      agricultural soils worldwide. However, there is still controversy about their
      degradation and accumulation in soils. In this study, (14)C-labelled Cry1Ab
      protein was applied to soil microcosms at two concentrations (14 and 50 MUg g(-1)
      soil) to quantify the mineralization of Cry1Ab, its incorporation into the soil
      microbial biomass, and its persistence in two soils which strongly differed in
      their texture but not in silt or pH. Furthermore, ELISA was used to quantify
      Cry1Ab and its potential immunoreactive breakdown products in aqueous soil
      extracts. In both soils, (14)CO2-production was initially very high and then
      declined during a total monitoring period of up to 135 days. A total of 16 to 23
      % of the (14)C activity was incorporated after 29 to 37 days into the soil
      microbial biomass, indicating that Cry1Ab protein was utilized by microorganisms
      as a growth substrate. Adsorption in the clay-rich soil was the most important
      factor limiting microbial degradation; as indicated by higher degradation rates
      in the more sandy soil, extremely low concentrations of immunoreactive Cry1Ab
      molecules in the soils' aqueous extracts and a higher amount of (14)C activity
      bound to the soil with more clay. Ecological risk assessments of Bt-crops should
      therefore consider that the very low concentrations of extractable Cry1Ab do not
      reflect the actual elimination of the protein from soils but that, on the other
      hand, desorbed proteins mineralize quickly due to efficient microbial
      degradation.

PMID- 25967659
TI  - Domestic wastewater treatment in a novel sequencing batch biofilm filter.
AB  - Biological treatment of domestic sewage low C/N ratio was accomplished in a pilot
      scale sequencing batch biofilm filter (SBBF). The novel hybrid bioreactor
      consisted of bio-band in the upper and anthracite filter media in the bottom,
      which combined a sequencing batch biofilm reactor (SBBR) with a biological
      filter. The average removal efficiency values of chemical oxygen demand (COD),
      ammonium nitrogen (NH4 (+)-N), total nitrogen (TN), and total phosphorus (TP)
      were 89.4, 83.3, 62.9, and 48.7%, respectively. A 454-pyrosequencing technology
      was employed to investigate the microbial communities of the influent (J1) and
      the biofilm (J2) on the bio-band on day 40. Pyrosequencing analysis of the 16S
      rRNA gene revealed the community of the biofilm consisted of Gammaproteobacteria
      (48.6%), Planctomycetacia (18.0%), Alphaproteobacteria (13.7%), Clostridia
      (9.6%), Desulfonatronum (18.5%), Actinobacteria (1.9%), and Bacilli (1.7%),
      accounting for 93.6% of total operational taxonomic units at genera level.
      Acinetobacter tjernbergiae and Acinetobacter lwoffii were the most abundant
      species, suggesting that denitrifying phosphorus removal was achieved in the
      SBBF.

PMID- 25967658
TI  - Description of the first fungal dye-decolorizing peroxidase oxidizing
      manganese(II).
AB  - Two phylogenetically divergent genes of the new family of dye-decolorizing
      peroxidases (DyPs) were found during comparison of the four DyP genes identified
      in the Pleurotus ostreatus genome with over 200 DyP genes from other
      basidiomycete genomes. The heterologously expressed enzymes (Pleos-DyP1 and Pleos
      DyP4, following the genome nomenclature) efficiently oxidize anthraquinoid dyes
      (such as Reactive Blue 19), which are characteristic DyP substrates, as well as
      low redox-potential dyes (such as 2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonic
      acid)) and substituted phenols. However, only Pleos-DyP4 oxidizes the high redox
      potential dye Reactive Black 5, at the same time that it displays high thermal
      and pH stability. Unexpectedly, both enzymes also oxidize Mn(2+) to Mn(3+),
      albeit with very different catalytic efficiencies. Pleos-DyP4 presents a Mn(2+)
      turnover (56 s(-1)) nearly in the same order of the two other Mn(2+)-oxidizing
      peroxidase families identified in the P. ostreatus genome: manganese peroxidases
      (100 s(-1) average turnover) and versatile peroxidases (145 s(-1) average
      turnover), whose genes were also heterologously expressed. Oxidation of Mn(2+)
      has been reported for an Amycolatopsis DyP (24 s(-1)) and claimed for other
      bacterial DyPs, albeit with lower activities, but this is the first time that
      Mn(2+) oxidation is reported for a fungal DyP. Interestingly, Pleos-DyP4
      (together with ligninolytic peroxidases) is detected in the secretome of P.
      ostreatus grown on different lignocellulosic substrates. It is suggested that
      generation of Mn(3+) oxidizers plays a role in the P. ostreatus white-rot
      lifestyle since three different families of Mn(2+)-oxidizing peroxidase genes are
      present in its genome being expressed during lignocellulose degradation.

PMID- 25967660
TI  - Zundel-like and Eigen-like hydrated protons on a platinum surface.
AB  - The nature of hydrated protons is an important topic in the fundamental study of
      electrode processes in acidic environment. For example, it is not yet clear
      whether hydrated protons are formed in the solution or on the electrode surface
      in the hydrogen evolution reaction on a Pt electrode. Using mass spectrometry and
      infrared spectroscopy, we show that hydrogen atoms are converted into hydrated
      protons directly on a Pt(111) surface coadsorbed with hydrogen and water in
      ultrahigh vacuum. The hydrated protons are preferentially stabilized as multiply
      hydrated species (H5 O2 (+) and H7 O3 (+) ) rather than as hydronium (H3 O(+) )
      ions. These surface-bound hydrated protons may play an important role in the
      interconversion between adsorbed hydrogen atoms and solvated protons in solution.

PMID- 25967661
TI  - A clinical study of integrating acupuncture and Western medicine in treating
      patients with Parkinson's disease.
AB  - Complementary therapy with acupuncture for Parkinson's disease (PD) has been
      studied for quite a long time, but the effectiveness of the treatment still
      remains unclear. The aim of this study is to evaluate the integrated effects of
      acupuncture treatment in PD patients who received western medicine. In the short
      term acupuncture treatment study, 20 patients received acupuncture therapy twice
      a week in acupoints DU 20, GB 20, LI 11, LI 10, LI 4, GB 31, ST 32, GB 34 and GB
      38 along with western medicine for 18 weeks, and 20 controlled patients received
      western medicine only. In the long-term acupuncture treatment, 13 patients
      received acupuncture treatment twice a week for 36 weeks. The outcome parameters
      include Unified Parkinson's disease rating scale (UPDRS), Beck Anxiety Inventory
      (BAI), Beck Depression Inventory-Version 2 (BDI-II), and WHO quality of life
      (WHOQOL). In the short-term clinical trial, a higher percentage of patients in
      the acupuncture group had score improvement in UPDRS total scores (55% vs. 15%, p
      = 0.019), sub-score of mind, behavior and mood (85% vs. 25%, p < 0.001), activity
      of daily living (65% vs. 15%, p = 0.003), mobility (40% vs. 15%, p = 0.155) and
      complication of treatment (75% vs. 15%, p < 0.001), BDI-II score (85% vs. 35%, p
      = 0.003), and WHOQOL score (65% vs. 15%, p = 0.003) when compared to control
      group at the end of the 18 weeks' follow up. After 36 weeks of long-term
      acupuncture treatment, the mean UPDRS total scores and sub-score of mentation,
      behavior and mood, sub-score of complications of therapy and BDI-II score
      decreased significantly when compared to the pretreatment baseline. In
      conclusion, acupuncture treatment had integrated effects in reducing symptoms and
      signs of mind, behavior, mood, complications of therapy and depression in PD
      patients who received Western medicine. 

PMID- 25967662
TI  - Effects of the inhaled treatment of liriope radix on an asthmatic mouse model.
AB  - As a treatment for allergic asthma, inhaled treatments such as bronchodilators
      that contain beta2-agonists have an immediate effect, which attenuates airway
      obstructions and decreases airway hypersensitivity. However, bronchodilators only
      perform on a one off basis, but not consistently. Asthma is defined as a chronic
      inflammatory disease of the airways accompanying the overproduction of mucus,
      airway wall remodeling, bronchial hyperreactivity and airway obstruction. Liriope
      platyphylla radix extract (LPP), a traditional Korean medicine, has been
      thoroughly studied and found to be an effective anti-inflammatory medicine. Here,
      we demonstrate that an inhaled treatment of LPP can attenuate airway
      hyperresponsiveness (AHR) in an ovalbumin-induced asthmatic mouse model, compared
      to the saline-treated group (p < 0.01). Moreover, LPP decreases inflammatory
      cytokine levels, such as eotaxin (p < 0.05), IL-5 (p < 0.05), IL-13 (p < 0.001),
      RANTES (p < 0.01), and TNF-alpha (p < 0.05) in the bronchoalveolar lavage (BAL)
      fluid of asthmatic mice. A histopathological study was carried out to determine
      the effects of LPP inhalation on mice lung tissue. We performed UPLC/ESI-QTOF-MS,
      LC/MS, and GC/MS analyses to analyze the chemical constituents of LPP, finding
      that these are ophiopogonin D, spicatoside A, spicatoside B, benzyl alcohol, and
      5-hydroxymethylfurfural. This study demonstrates the effect of an inhaled LPP
      treatment both on airway AHR and on the inflammatory response in an asthmatic
      mouse model. Hence, LPP holds significant promise as a nasal inhalant for the
      treatment of asthmatic airway disease. 

PMID- 25967663
TI  - Apocynum venetum Attenuates Acetaminophen-Induced Liver Injury in Mice.
AB  - Apocynum venetum L. (A. venetum) has long been used in oriental folk medicine for
      the treatment of some liver diseases; however, the underlying mechanisms remain
      to be fully elucidated. Acetaminophen (APAP) is a widely used analgesic drug that
      can cause acute liver injury in overdose situations. In this study, we
      investigated the potential protective effect of A. venetum leaf extract (ALE)
      against APAP-induced hepatotoxicity. Mice were intragastrically administered with
      ALE once daily for 3 consecutive days prior to receiving a single intraperitoneal
      injection of APAP. The APAP group showed severe liver injury characterized by the
      noticeable fluctuations in the following parameters: serum aminotransferases;
      hepatic malondialdehyde (MDA), 3-nitrotyrosine (3-NT), superoxide dismutase
      (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione
      (GSH). These liver damages induced by APAP were significantly attenuated by ALE
      pretreatments. A collective analysis of histopathological examination, DNA
      laddering and western blot for caspase-3 and cytochrome c indicated that the ALE
      is also capable of preventing APAP-induced hepatocyte death. Hyperoside,
      isoquercitrin and their derivatives have been identified as the major components
      of ALE using HPLC-MS/MS. Taken together, the A. venetum possesses
      hepatoprotective effects partially due to its anti-oxidant action.

PMID- 25967664
TI  - The Hexane Fraction of cyperus rotundus Prevents Non-Alcoholic Fatty Liver
      Disease Through the Inhibition of Liver X Receptor alpha-Mediated Activation of
      Sterol Regulatory Element Binding Protein-1c.
AB  - The goals of this study were (1) to examine the effects of Cyperus rotundus (CR)
      rhizome on cellular lipogenesis and non-alcoholic/diet-induced fatty liver
      disease, and (2) to elucidate the molecular mechanism behind its actions. The
      present investigation showed that the hexane fraction of CR rhizome (CRHF)
      reduced the elevated transcription levels of sterol regulatory element binding
      protein-1c (SREBP-1c) in primary hepatocytes following exposure to the liver X
      receptor alpha (LXRalpha) agonist. The SREBP-1c gene is a master regulator of
      lipogenesis and a key target of LXRalpha. CRHF inhibited not only the LXRalpha
      dependent activation of the synthetic LXR response element (LXRE) promoter, but
      also the activation of the natural SREBP-1c promoter. Moreover, CRHF decreased
      (a) the recruitment of RNA polymerase II to the LXRE of the SREBP-1c gene; (b)
      the LXRalpha-dependent up-regulation of various lipogenic genes; and (c) the
      LXRalpha-mediated accumulation of triglycerides in primary hepatocytes.
      Furthermore, CRHF ameliorated fatty liver disease and reduced the expression
      levels of hepatic lipogenic genes in high sucrose diet (HSD)-fed mice.
      Interestingly, CRHF did not affect the expression of ATP-binding cassette
      transporter A1, another important LXR target gene that is required for reverse
      cholesterol transport (RCT) and protects against atherosclerosis. Taken together,
      these results suggest that CRHF might be a novel therapeutic remedy for fatty
      liver disease through the selective inhibition of the lipogenic pathway. 

PMID- 25967665
TI  - Ostericum koreanum Reduces LPS-Induced Bone Loss Through Inhibition of
      Osteoclastogenesis.
AB  - The roots of Ostericum koreanum (OK) Maximowicz have traditionally been used to
      produce an herbal medicine reported to possess anti-inflammatory, anti-oxidant,
      antimicrobial, and antitumor activities; however, its effect on bone metabolism
      has not yet been reported. The present study examined the effects of OK extract
      on lipopolysaccharide (LPS)-induced bone loss in mice by investigating bone
      structure and the levels of the receptor activator of nuclear factor kappa-B
      ligand (RANKL) and osteoprotegerin (OPG) in serum and bone marrow fluid (BMF).
      The effects of OK extract on osteoclastogenesis were also investigated in mouse
      bone marrow macrophages by examining the formation of tartrate-resistant acid
      phosphatase (TRAP)-positive cells, the actin ring, and bone resorption activity.
      OK reduced LPS-induced bone destruction in vivo via a decrease in the RANKL/OPG
      ratio. Furthermore, it suppressed the formation of TRAP-positive cells and the
      actin ring, and reduced the bone-resorbing activity of mature osteoclasts. OK
      also significantly down-regulated the expression of various osteoclast-specific
      genes. However, it did not affect osteoblast differentiation, or the expression
      of genes involved in this process. These results demonstrated that OK prevented
      LPS-induced bone loss by decreasing the RANKL/OPG ratio in serum and BMF, and
      inhibited osteoclast differentiation and function, suggesting that OK represents
      a potential therapeutic drug for the treatment of osteoclast-associated bone
      diseases. 

PMID- 25967666
TI  - Undaria pinnatifida Promotes Spinogenesis and Synaptogenesis and Potentiates
      Functional Presynaptic Plasticity in Hippocampal Neurons.
AB  - Reductions in neurotrophic factors are implicated in synaptic dysfunction in the
      central nervous system, but exogenous neurotrophic factors with potential effects
      on neuritic regeneration and synaptic reconstruction could offer therapeutic and
      preventive strategies for treating memory-related neurological disorders. In an
      earlier effort to identify natural neurotrophic agents, we found that the ethanol
      extract of the edible marine alga Undaria pinnatifida (UPE) had promising effects
      on the neuritogenesis of cultured hippocampal neurons. Here, we further
      investigated the ability of UPE to promote spinogenesis and synaptogenesis in
      primary cultures of hippocampal neurons. It was found that UPE triggered
      significant increase in numbers of dendritic filopodia and spines, promoted the
      formation of excitatory and inhibitory synapses, and potentiated synaptic
      transmission by increasing the sizes of reserve vesicle pools at presynaptic
      terminals. These findings indicate a substantial role for UPE in the
      morphological and functional maturation of neurons and suggest that UPE is a
      possible therapeutic preventative measure and treatment for neurodegenerative
      diseases, such as those involving cognitive disorders and memory impairments. 

PMID- 25967668
TI  - Artocarpus communis Induces Autophagic Instead of Apoptotic Cell Death in Human
      Hepatocellular Carcinoma Cells.
AB  - For centuries, natural plant extracts have played an important role in
      traditional medicine for curing and preventing diseases. Studies have revealed
      that Artocarpus communis possess various bioactivities, such as anti
      inflammation, anti-oxidant, and anticancer activities. A. communis offers
      economic value as a source of edible fruit, yields timber, and is widely used in
      folk medicines. However, little is known about its molecular mechanisms of
      anticancer activity. Here, we demonstrate the antiproliferative activity of A.
      communis methanol extract (AM) and its dichloromethane fraction (AD) in two human
      hepatocellular carcinoma (HCC) cell lines, HepG2 and PLC/PRF/5. Colony assay
      showed the long-term inhibitory effect of both extracts on cell growth. DNA
      laddering and immunoblotting analyses revealed that both extracts did not induce
      apoptosis in the hepatoma cell lines. AM and AD-treated cells demonstrated
      different cell cycle distribution compared to UV-treated cells, which presented
      apoptotic cell death with high sub-G1 ratio. Instead, acridine orange staining
      revealed that AM and AD triggered autophagosome accumulation. Immunoblotting
      showed a significant expression of autophagy-related proteins, which indicated
      the autophagic cell death (ACD) of hepatoma cell lines. This study therefore
      demonstrates that A. communis AM and its dichloromethane fraction can induce ACD
      in HCC cells and elucidates the potential of A. communis extracts for development
      as anti tumor therapeutic agents that utilize autophagy as mechanism in mediating
      cancer cell death. 

PMID- 25967667
TI  - Paeoniflorin, a Monoterpene Glycoside, Protects the Brain from Cerebral Ischemic
      Injury via Inhibition of Apoptosis.
AB  - Paeoniflorin (PF) is a principal bioactive component, which exhibits many
      pharmacological effects, including protection against ischemic injury. This paper
      aimed to investigate the protective effect of PF both in vivo and in vitro.
      Middle cerebral artery occlusion (MCAO) was performed on male Sprague-Dawley (SD)
      rat for 2 h, and different doses of PF or vehicle were administered 2 h after
      reperfusion. Rats were sacrificed after 7 days treatment of PF/vehicle. PF
      treatment for 7 days ameliorated MCAO-induced neurological deficit and decreased
      the infarct area. Further study demonstrated that PF inhibited the over
      activation of astrocytes and apoptosis of neurons, and PF promoted up-regulation
      of neuronal specific marker neuron-specific nuclear (NeuN) and microtubule
      associated protein 2 (MAP-2) in brain. Moreover, NMDA-induced neuron apoptosis
      was employed. The in vitro study revealed that PF treatment protected against
      NMDA-induced cell apoptosis and neuronal loss via up-regulation of neuronal
      specific marker NeuN, MAP-2 and Bcl-2 and the down-regulation Bax. Taken
      together, the present study demonstrates that PF produces its protective effect
      by inhibiting the over-activation of astrocytes, apoptosis of neurons and up
      regulation of neuronal specific marker NeuN, MAP-2, and B-cell lymphoma-2 (Bcl
      2), and down-regulation Bax. Our study reveals that PF may be a potential
      neuroprotective agent for stroke and can provide basic data for clinical use. 

PMID- 25967669
TI  - Cantharidin Induces Apoptosis Through the Calcium/PKC-Regulated Endoplasmic
      Reticulum Stress Pathway in Human Bladder Cancer Cells.
AB  - Bladder cancer is a common malignancy worldwide. However, there is still no
      effective therapy for bladder cancer. In this study, we investigated the
      cytotoxic effects of cantharidin [a natural toxin produced (pure compound) from
      Chinese blister beetles (Mylabrisphalerata or Mylabriscichorii) and Spanish flies
      (Cantharis vesicatoria)] in human bladder cancer cell lines (including: T24 and
      RT4 cells). Treatment of human bladder cancer cells with cantharidin
      significantly decreased cell viability. The increase in the expressions of
      caspase-3 activity and cleaved form of caspase-9/-7/-3 were also increased in
      cantharidin-treated T24 cells. Furthermore, cantharidin increased the levels of
      phospho-eIF2alpha and Grp78 and decreased the protein expression of procaspase
      12, which was accompanied by the increase in calpain activity in T24 cells.
      Cantharidin was capable of increasing the intracellular Ca (2+) and the
      phosphorylation of protein kinase C (PKC) in T24 cells. The addition of BAPTA/AM
      (a Ca (2+) chelator) and RO320432 (a selective cell-permeable PKC inhibitor)
      effectively reversed the increase in caspase-3 and calpain activity, the
      phosphorylation levels of PKC and eIF2alpha and Grp78 protein expression, and the
      decrease in procaspase-12 expression induced by cantharidin. Importantly,
      cantharidin significantly decreased the tumor volume (a dramatic 71% reduction
      after 21 days of treatment) in nude mice xenografted with T24 cells. Taken
      together, these results indicate cantharidin induced human bladder cancer cell
      apoptosis through a calcium/PKC-regulated ER stress pathway. These findings
      suggest that cantharidin may be a novel and potential anticancer agent targeting
      on bladder cancer cells. 

PMID- 25967670
TI  - A longitudinal survey of African swine fever in Uganda reveals high apparent
      disease incidence rates in domestic pigs, but absence of detectable persistent
      virus infections in blood and serum.
AB  - BACKGROUND: African swine fever (ASF) is a fatal, haemorrhagic disease of
      domestic pigs, that poses a serious threat to pig farmers and is currently
      endemic in domestic pigs in most of sub-Saharan Africa. To obtain insight into
      the factors related to ASF outbreaks at the farm-level, a longitudinal study was
      performed in one of the major pig producing areas in central Uganda. Potential
      risk factors associated with outbreaks of ASF were investigated including the
      possible presence of apparently healthy ASF-virus (ASFV) infected pigs, which
      could act as long-term carriers of the virus. Blood and serum were sampled from
      715 pigs (241 farms) and 649 pigs (233 farms) to investigate presence of ASFV and
      antibodies, during the periods of June-October 2010 and March-June 2011,
      respectively. To determine the potential contribution of different risks to ASF
      spread, a questionnaire-based survey was administered to farmers to assess the
      association between ASF outbreaks during the study period and the risk factors.
      RESULTS: Fifty-one (21 %) and 13 (5.6 %) farms reported an ASF outbreak on their
      farms in the previous one to two years and during the study period, respectively.
      The incidence rate for ASF prior to the study period was estimated at 14.1 per
      100 pig farm-years and 5.6 per 100 pig farm-years during the study. Three pigs
      tested positive for ASFV using real-time PCR, but none tested positive for ASFV
      specific antibodies using two different commercial ELISA tests. CONCLUSIONS:
      There was no evidence for existence of pigs that were long-term carriers for the
      virus based on the analysis of blood and serum as there were no seropositive pigs
      and the only three ASFV DNA positive pigs were acutely infected and were linked
      to outbreaks reported by farmers during the study. Potential ASF risk factors
      were present on both small and medium-scale pig farms, although small scale farms
      exhibited a higher proportion with multiple potential risk factors (like
      borrowing boars for sows mating, buying replacement from neighboring farms
      without ascertaining health status, etc) and did not implement any biosecurity
      measures. However, no risk factors were significantly associated with ASF reports
      during the study.

PMID- 25967671
TI  - Genome-wide association analysis identifies three new risk loci for gout
      arthritis in Han Chinese.
AB  - Gout is one of the most common types of inflammatory arthritis, caused by the
      deposition of monosodium urate crystals in and around the joints. Previous genome
      wide association studies (GWASs) have identified many genetic loci associated
      with raised serum urate concentrations. However, hyperuricemia alone is not
      sufficient for the development of gout arthritis. Here we conduct a multistage
      GWAS in Han Chinese using 4,275 male gout patients and 6,272 normal male controls
      (1,255 cases and 1,848 controls were genome-wide genotyped), with an additional
      1,644 hyperuricemic controls. We discover three new risk loci, 17q23.2
      (rs11653176, P=1.36 * 10(-13), BCAS3), 9p24.2 (rs12236871, P=1.48 * 10(-10),
      RFX3) and 11p15.5 (rs179785, P=1.28 * 10(-8), KCNQ1), which contain inflammatory
      candidate genes. Our results suggest that these loci are most likely related to
      the progression from hyperuricemia to inflammatory gout, which will provide new
      insights into the pathogenesis of gout arthritis. 

PMID- 25967672
TI  - Dimethyl fumarate modulates antioxidant and lipid metabolism in oligodendrocytes.
AB  - Oxidative stress contributes to pathology associated with inflammatory brain
      disorders and therapies that upregulate antioxidant pathways may be
      neuroprotective in diseases such as multiple sclerosis. Dimethyl fumarate, a
      small molecule therapeutic for multiple sclerosis, activates cellular antioxidant
      signaling pathways and may promote myelin preservation. However, it is still
      unclear what mechanisms may underlie this neuroprotection and whether dimethyl
      fumarate affects oligodendrocyte responses to oxidative stress. Here, we examine
      metabolic alterations in oligodendrocytes treated with dimethyl fumarate by using
      a global metabolomic platform that employs both hydrophilic interaction liquid
      chromatography-mass spectrometry and shotgun lipidomics. Prolonged treatment of
      oligodendrocytes with dimethyl fumarate induces changes in citric acid cycle
      intermediates, glutathione, and lipids, indicating that this compound can
      directly impact oligodendrocyte metabolism. These metabolic alterations are also
      associated with protection from oxidant challenge. This study provides insight
      into the mechanisms by which dimethyl fumarate could preserve myelin integrity in
      patients with multiple sclerosis. 

PMID- 25967673
TI  - Hyperoxia activates ATM independent from mitochondrial ROS and dysfunction.
AB  - High levels of oxygen (hyperoxia) are often used to treat individuals with
      respiratory distress, yet prolonged hyperoxia causes mitochondrial dysfunction
      and excessive reactive oxygen species (ROS) that can damage molecules such as
      DNA. Ataxia telangiectasia mutated (ATM) kinase is activated by nuclear DNA
      double strand breaks and delays hyperoxia-induced cell death through downstream
      targets p53 and p21. Evidence for its role in regulating mitochondrial function
      is emerging, yet it has not been determined if mitochondrial dysfunction or ROS
      activates ATM. Because ATM maintains mitochondrial homeostasis, we hypothesized
      that hyperoxia induces both mitochondrial dysfunction and ROS that activate ATM.
      In A549 lung epithelial cells, hyperoxia decreased mitochondrial respiratory
      reserve capacity at 12h and basal respiration by 48 h. ROS were significantly
      increased at 24h, yet mitochondrial DNA double strand breaks were not detected.
      ATM was not required for activating p53 when mitochondrial respiration was
      inhibited by chronic exposure to antimycin A. Also, ATM was not further activated
      by mitochondrial ROS, which were enhanced by depleting manganese superoxide
      dismutase (SOD2). In contrast, ATM dampened the accumulation of mitochondrial ROS
      during exposure to hyperoxia. Our findings suggest that hyperoxia-induced
      mitochondrial dysfunction and ROS do not activate ATM. ATM more likely carries
      out its canonical response to nuclear DNA damage and may function to attenuate
      mitochondrial ROS that contribute to oxygen toxicity.

PMID- 25967674
TI  - Prevalence of the UGT1A1*6 (c.211G>A) Polymorphism and Prediction of Irinotecan
      Toxicity in Iranian Populations of Different Ethnicities.
AB  - BACKGROUND: Pharmacogenetic studies on irinotecan treatment in patients with
      metastatic colorectal cancer have indicated that genetic polymorphisms in
      UGT1A1*6 can lead to decreased enzyme activity and accumulation of the toxic
      metabolite SN-38. Here, we compared the prevalence of UGT1A1*6 in an Iranian
      population of different ethnicities with those of other populations. MATERIALS
      AND METHODS: A total of 300 healthy people of different ethnic groups including
      Persian, Azari, Lure, Kurdish, Arab, Baluch and Caspian in the Iranian population
      were enrolled. Genotyping of the UGT1A1*6 alleles (G/G, A/G, A/A) was performed
      by polymerase chain reaction-restriction fragment length polymorphism and direct
      genomic DNA sequencing. RESULT: The most predictive genotype among the Iranian
      ethnic groups, especially Persian, was the G/G genotype (wild-type genotype). The
      frequency of the A/G genotype among the Persian, Azari, Lure, Kurdish, Arab,
      Baluch and Caspian ethnicities were 15.69% (n = 27), 11.11% (n = 8), 5.88% (n =
      1), 9.09% (n = 1), 10% (n = 1), 20% (n = 1) and 0% (n = 0), respectively. Only
      one person with Persian ethnicity was homozygous for the mutation in UGT1A1*6
      (0.58%). Additionally, the frequency of the A and G alleles in Iranians was 6.83
      and 93.16%, respectively. CONCLUSION: The identification of the UGT1A1*6 alleles
      is necessary among the different Iranian ethnic groups before irinotecan therapy,
      suggesting that genotyping would be helpful for clinicians to optimize
      chemotherapy or identify individuals at risk of adverse drug reactions before
      clinical trials.

PMID- 25967675
TI  - Synthesis and investigation of antimicrobial activity and spectrophotometric and
      dyeing properties of some novel azo disperse dyes based on naphthalimides.
AB  - A series of novel disperse dyes containing azo group were synthesized through a
      diazotization and coupling process. The 4-amino-N-2-aminomethylpyridine-1,8
      naphthalimide was diazotized by nitrosylsulphuric acid and coupled with various
      aromatic amines such as N,N-diethylaniline, N,N-dihydroxyethylaniline, 8
      hydroxyquinoline, and 2-methylindole. Chemical structures of the synthesized dyes
      were characterized by Fourier transform infrared (FTIR), differential scanning
      calorimetry (DSC), proton nuclear magnetic resonance ((1) H NMR), carbon nuclear
      magnetic resonance ((13) C NMR), elemental analysis, and ultraviolet-visible (UV
      visible) spectroscopy. The spectrophotometric data of all dyes were evaluated in
      various solvents with different polarity. Eventually, the dyes were applied on
      polyamide fabrics in order to investigate their dyeing properties. The fastness
      properties of the dyed fabrics such as wash, light, and rubbing fastness degrees
      were measured by standard methods. Moreover, the color gamut of the synthesized
      dyes was measured on polyamide fabrics. Results indicated that some of the
      synthesized dyes were able to dye polyamide fabrics with deep shades. They had
      very good wash and rubbing fastness degrees and moderate-to-good light fastness
      on polyamide fabrics. The antibacterial and antifungal activities of the
      synthesized dyes were evaluated in soluble state and on the dyed fabrics. The
      results indicated that dye 2 containing N,N-dihydroxyethylaniline as coupler had
      the highest activity against all the bacteria and fungi used.

PMID- 25967676
TI  - Pazopanib for metastatic pulmonary epithelioid hemangioendothelioma-a suitable
      treatment option: case report and review of anti-angiogenic treatment options.
AB  - BACKGROUND: Epithelioid hemangioendothelioma is a rare vascular tumor of
      borderline or low-grade malignancy. The lungs and liver are the two common
      primary organs affected. Metastatic disease was reported in more than 100 cases
      in the literature. However, no firm conclusions can be determined for recommended
      treatment options. CASE PRESENTATION: The current case presents a patient with
      metastatic pulmonary epithelioid hemangioendothelioma to the cervical and
      mediastinal lymph nodes, lungs and liver that has been treated with pazopanib for
      more than two years with PET avid complete metabolic response in the mediastinum
      and lungs, and long-lasting stable disease. Target therapies that block VEGFR
      have a logical base in this rare malignancy. CONCLUSIONS: The current case is the
      first to report objective, long-lasting response to pazopanib.

PMID- 25967677
TI  - Selective Dissolution of A-Site Cations in ABO3 Perovskites: A New Path to High
      Performance Catalysts.
AB  - Selective dissolution is a common corrosion process in dealloying in which an
      alloy is immersed in acid to remove the active element, leaving behind an inert
      constituent. We introduce this technique into the treatment of oxide catalysts. A
      three-dimensionally ordered macroporous LaMnO3 perovskite has been prepared and
      treated with diluted HNO3 to selectively remove La cations, acquiring a novel
      gamma-MnO2-like material. LaMnO3 is not a satisfactory catalyst on CO oxidation.
      Upon the removal of La cations, the obtained sample showed a significantly higher
      CO oxidation catalytic activity (T50=89  degrees C) than the initial precursor
      LaMnO3 (T50=237  degrees C) and ordinary gamma-MnO2 (T50=148  degrees C). A large
      surface area, a high degree of mesoporosity, excellent low-temperature
      reducibility, and especially improved surface oxygen species are deduced to be
      responsible for CO oxidation at lower temperatures.

PMID- 25967678
TI  - Difficulties in emotion regulation and problem drinking in young women: the
      mediating effect of metacognitions about alcohol use.
AB  - INTRODUCTION: The aim of the current study was to examine, in a sample of women
      aged 18 25, the association between difficulties in emotion regulation,
      metacognitions about alcohol use and problem drinking. According to metacognitive
      model of problem drinking, it was assumed that metacognitions are potential
      mediators in the relationship between emotional dysregulation and problem
      drinking. METHODS: A total sample of 502 women was recruited. They were
      administered a questionnaire identifying problem drinking (AUDIT), the
      Difficulties in Emotion Regulation Scale (DERS) and two scales measuring
      metacognitions about alcohol use: the Positive Alcohol Metacognitions Scale
      (PAMS) and the Negative Alcohol Metacognitions Scale (NAMS). A structural
      equation model of the relationships between emotional dysregulation and problem
      drinking - including a mediating role of metacognitions concerning alcohol use -
      was tested. RESULTS: No direct association between emotional dysregulation and
      problem drinking was observed. A relationship between those variables became
      apparent once metacognitions were considered as a mediator; however, only
      positive metacognitions about alcohol use emerged as a significant predictor of
      drinking behavior, and as a full mediator of the relationship between emotion
      dysregulation and problem drinking. CONCLUSIONS: The results provide evidence for
      a metacognitive conceptualization of problem drinking. They emphasize the role of
      positive metacognitions about alcohol use. However, this result could be age
      specific; it confirms previous findings that, in samples of young people,
      drinking is primarily related to positive metacognitions concerning cognitive
      emotional self-regulation.

PMID- 25967679
TI  - Secondhand smoke exposure and other correlates of susceptibility to smoking: a
      propensity score matching approach.
AB  - Secondhand smoke (SHS) exposure is responsible for numerous diseases of the lungs
      and other bodily systems among children. In addition to the adverse health
      effects of SHS exposure, studies show that children exposed to SHS are more
      likely to smoke in adolescence. Susceptibility to smoking is a measure used to
      identify adolescent never-smokers who are at risk for smoking. Limited research
      has been conducted on the influence of SHS on susceptibility to smoking. The
      purpose of this study was to determine a robust measure of the strength of
      correlation between SHS exposure and susceptibility to smoking among never
      smoking U.S. adolescents. This study used data from the 2009 National Youth
      Tobacco Survey to identify predictors of susceptibility to smoking in the full
      (pre-match) sample of adolescents and a smaller (post-match) sample created by
      propensity score matching. Results showed a significant association between SHS
      exposure and susceptibility to smoking among never-smoking adolescents in the pre
      match (OR=1.47) and post-match (OR=1.52) samples. The odds ratio increase after
      matching suggests that the strength of the relationship was underestimated in the
      pre-match sample. Other significant correlates of susceptibility to smoking
      identified include: gender, race/ethnicity, personal income, smoke-free home
      rules, number of smoking friends, perception of SHS harm, perceived benefits of
      smoking, and exposure to pro-tobacco media messages. The use of propensity score
      matching procedures reduced bias in the post-match sample, and provided a more
      robust estimate of the influence of SHS exposure on susceptibility to smoking,
      compared to the pre-match sample estimates. 

PMID- 25967680
TI  - Factors Associated with Adverse Events during Tracheal Intubation in the NICU.
AB  - BACKGROUND: The incidence of adverse tracheal intubation-associated events
      (TIAEs) and associated patient, practice, and intubator characteristics in the
      neonatal intensive care unit (NICU) setting are unknown. OBJECTIVES: To determine
      the incidence of adverse TIAEs and to identify factors associated with TIAEs in
      the NICU. METHODS: Single-site prospective observational cohort study of infants
      who were intubated in a level 4 referral NICU between September 1, 2011 and
      November 30, 2013. A standardized pediatric airway registry was implemented to
      document patient, practice, and intubator characteristics and outcomes of
      intubation encounters. The primary outcome was adverse TIAEs. RESULTS: Adverse
      TIAEs occurred in 153 of 701 (22%) tracheal intubation encounters. Factors that
      were independently associated with lower incidence of TIAEs in logistic
      regression included attending physician (vs. resident; odds ratio (OR) 0.4, 95%
      CI: 0.16, 0.98) and use of paralytic medication (OR 0.45, 95% CI: 0.25, 0.81).
      Severe oxygen desaturations (>= 20% decrease in oxygen saturation) occurred in
      51.1% of encounters and were more common in tracheal intubations performed by
      residents (62.8%), compared to fellows (43.2%) or attendings (47.5%; p = 0.008).
      CONCLUSIONS: Adverse TIAEs and severe oxygen desaturation events are common in
      the NICU setting. Modifiable risk factors associated with TIAEs identified
      include intubator training level and use of paralytic medications.

PMID- 25967682
TI  - Erlotinib in second-line therapy for non-small cell lung cancer - A clinical
      case.
AB  - the epidermal growth-factor receptor (EGFR) and its signaling pathway have become
      a major target for therapy of non-small cell lung cancer (NSCLC). After the BR.21
      study showed its effectiveness and its tolerability in older patients, erlotinib,
      a specific EGFR tyrosine-kinase inhibitor, has been approved for NSCLC therapy
      after failure of treatment with at least one line of chemotherapy (CT). The
      authors present the case of a 63 years-old female patient, with a history of
      angina pectoris, who was diagnosed with a lung adenocarcinoma. Because of poor
      tolerance to first-line CT, she had second-line treatment with erlotinib. There
      was a good response to therapy, along with symptomatic improvement. Adverse
      effects were light to moderate, well tolerated, and required no dose reduction.
      Rev Port Pneumol 2008; XIV (Supl 3): S17-S22. 

PMID- 25967683
TI  - Tyrosine kinase inhibitors in advanced NSCLC: A case report.
AB  - Erlotinib is a molecule that selectively inhibits epidermal growth factor
      receptor (EGFR) tyrosine kinase activity. The authors present a case that
      exemplifies the use of erlotinib as second line therapy for non-small cell lung
      cancer (NSCLC). This case is about a 76 years old woman, non-smoker, with
      advanced lung adenocarcinoma (stage IIIB) previously treated with two cycles of
      standard chemotherapy, which were interrupted by serious adverse reactions. Rev
      Port Pneumol 2008; XIV (Supl 3): S23-S28. 

PMID- 25967681
TI  - Nectin-1 spots as a novel adhesion apparatus that tethers mitral cell lateral
      dendrites in a dendritic meshwork structure of the developing mouse olfactory
      bulb.
AB  - Mitral cells project lateral dendrites that contact the lateral and primary
      dendrites of other mitral cells and granule cell dendrites in the external
      plexiform layer (EPL) of the olfactory bulb. These dendritic structures are
      critical for odor information processing, but it remains unknown how they are
      formed. In immunofluorescence microscopy, the immunofluorescence signal for the
      cell adhesion molecule nectin-1 was concentrated on mitral cell lateral dendrites
      in the EPL of the developing mouse olfactory bulb. In electron microscopy, the
      immunogold particles for nectin-1 were symmetrically localized on the plasma
      membranes at the contacts between mitral cell lateral dendrites, which showed
      bilateral darkening without dense cytoskeletal undercoats characteristic of
      puncta adherentia junctions. We named the contacts where the immunogold particles
      for nectin-1 were symmetrically accumulated "nectin-1 spots." The nectin-1 spots
      were 0.21 MUm in length on average and the distance between the plasma membranes
      was 20.8 nm on average. In 3D reconstruction of serial sections, clusters of the
      nectin-1 spots formed a disc-like structure. In the mitral cell lateral dendrites
      of nectin-1-knockout mice, the immunogold particles for nectin-1 were
      undetectable and the plasma membrane darkening was electron-microscopically
      normalized, but the plasma membranes were partly separated from each other. The
      nectin-1 spots were further identified between mitral cell lateral and primary
      dendrites and between mitral cell lateral dendrites and granule cell dendritic
      spine necks. These results indicate that the nectin-1 spots constitute a novel
      adhesion apparatus that tethers mitral cell dendrites in a dendritic meshwork
      structure of the developing mouse olfactory bulb.

PMID- 25967684
TI  - Erlotinib: A successful clinical case and some notes about hepatic toxicity.
AB  - A case of a woman with lung adenocarcinoma in which fifteen-month disease control
      was achieved with second-line erlotinib treatment is presented. Five months after
      treatment beginning, isolated grade 3 hyperbilirubinemia occurred and daily dose
      was reduced to 100mg. Comments on erlotinib hepatic toxicity and the
      pharmacologic interactions on erlotinib metabolism are given. Rev Port Pneumol
      2008; XIV (Supl 3): S29-S34. 

PMID- 25967685
TI  - Erlotinib and brain metastases.
AB  - We report two cases of brain metastases in context of non small cell lung cancer
      (NSCLC). After having progressed to chemotherapy they received erlotinib 150mg/m2
      orally daily, with complete response of brain metastasis and partial response of
      thoracic lesions. Brain metastases are both prevalent and a major cause of
      mortality in NSCLC, with few systemic treatment options. Median survival after
      whole brain radiotherapy is 4-6 months and the role of systemic therapy for brain
      metastases is limited with the most drugs use to stage IV disease ineffective in
      this setting. This case demonstrates that brain metastases may be sensitive to
      erlotinib and give to us growing body of evidence that EGFR-associated tyrosine
      kinase inhibition is a feasible strategy in the management of NSCLC patients with
      brain metastases We propose further study into the continued use of this drug in
      the situation where there is a differential response. Rev Port Pneumol 2008; XIV
      (Supl 3): S35-S42. 

PMID- 25967687
TI  - Erlotinib: An EGFR inhibitor with therapeutic benefit in non-small cell lung
      cancer.

PMID- 25967686
TI  - Treatment of advanced non small cell lung cancer with erlotinib. Two clinical
      cases.
AB  - Early studies with tirosine kinase inhibitors (TKI), namely Erlotinib and
      Gefitinib, in patients with non small cell lung cancer (NSCLC), showed that
      although most patients did not respond radiologically, a small percentage of
      those patients (about 10%) had an excellent response to treatment, with
      radiological regression and clinical response duration. Four patient populations
      are known as having better response to TKI as opposed to other patients:
      adenocarcinoma patients, non-smokers, women and asians. Nevertheless, a good
      general status remains a predictive factor for treatment response. The discovery
      of the EGFR mutation in NSCLC patients' tumors and its association with clinical
      response to Erlotinib and Gefitinib, confirmed by a considerable number of
      retrospective and prospective studies, showed that response rates are between 75
      80% in patients carrying this mutation. Although several mutations have been
      identified, the two commonest (approximately 90%) are located in exons 19 and 21.
      The authors present two patients studied and treated at the Pulmonology
      Department's Lung Oncology Unit of CHVNGaia, where Erlotinib was used as 3(rd)
      line treatment: in one patient, which was part of the population with good
      response to TKI, a classic exon 19 was identified, and was treated with Erlotinib
      for twenty months with clinical stability; the other patient did not belong to
      the above mentioned population and an Exon 20 mutation was identified (a mutation
      not yet described in literature, being not clear its association with response to
      treatment with TKI) - treatment was stopped after 7.4months due to disease
      progression. Rev Port Pneumol 2008; XIV (Supl 3): S43-S51. 

PMID- 25967688
TI  - Treatment of non-small cell lung cancer, advanced disease, with erlotinib in
      2(nd) and 3(rd) lines. Two cases report.
AB  - Agents that inhibit the activity of cell membrane receptor tyrosine kinases, such
      as the human epidermal growth factor receptor (EGFR) have been an attractive
      target because EGFR is expressed by 80% of NSCLC. Erlotinib as monotherapy in the
      treatment of NSCLC after failure of at least one prior chemotherapy regimen,
      prolonged survival and improved quality of life, although modest response rate.
      Women, Asiens, patients with Adenocarcinoma and never smokers, were more likely
      than other patients to have a response to erlotinib. This is the group of
      patients that most commonly have an EGFR mutation. The authors describe two
      cases, with important control of symptoms and increased time to progression,
      independently o response rate (stable disease or partial response). Rev Port
      Pneumol 2008; XIV (Supl 3): S53-S60. 

PMID- 25967689
TI  - Erlotinib as an alternative treatment for NSCLC. Case Report.
AB  - INTRODUCTION: Erlotinib is an approved treatment for NSCLC locally advanced or
      with metastases, after failure of initial chemotherapy. The authors present a
      NSCLC clinical case of great clinical and imaging improvement, with no drug
      induced toxicity observed, after treatment with erlotinib. CASE PRESENTATION: A
      76-year-old woman, never-smoker, had been diagnosed for lung adenocarcinoma,
      through thoracoscopy, after presenting a large-volume pleural effusion. At the
      time of diagnosis it was inoperable (stage IIIB - T4 N1 M0). She was submitted to
      two consecutive chemotherapy treatments with carboplatin+gemcitabin and
      pemetrexed, respectively. Due to its failure, with lack of response, erlotinib
      was set as the alternative choice, with great clinical and imaging improvement
      after 6 months of treatment. CONCLUSION: The authors recommend, even in the
      absence of EGFR result, the use of erlotinib when progression of the disease is
      seen, after initial chemotherapy, especially in lung adenocarcinoma and in never
      smokers. Rev Port Pneumol 2008; XIV (Supl 3): S61-S63.

PMID- 25967690
TI  - Non-small cell lung cancer patients treated with erlotinib - Clinical cases.
AB  - We present four patients with non-small cell lung cancer treated in second and
      third line with Erlotinib. These are selected patients that obtained a good
      clinical response. Almost all presented cutaneous side effects. Rev Port Pneumol
      2008; XIV (Supl 3): S65-S69. 

PMID- 25967691
TI  - Lung adenocarcinoma - For how long a good response is the question.
AB  - A 75 year old woman was observed at the emergency department with cough,
      hyperthermia and thoracic pain in October 2004.A pleural effusion was identified
      and studied. Thorax CT scan evidenced a pleural effusion and thickening in the
      RSL anterior segment but bronchofibroscopy only identified inflammatory changes.
      In February 2005 the pleural effusion relapsed and the CT scan showed nodular
      densification adjacent to LSLB and lingual. VATS converted to thoracotomy was
      preformed and followed by a long recover period. Histology of surgical specimen
      revealed an adenocarcinoma. First line CT was administered until progression as
      bone metastasis, in March 2006. Second line CT was started, with disease
      stabilization. The administration of erlotinib was started in July 2007 and
      continues to the present with good tolerance. The patient has no pain and
      continues without progression of disease after 13 month of treatment. For how
      long will she maintain this response, is the question. Rev Port Pneumol 2008; XIV
      (Supl 3): S71-S77. 

PMID- 25967693
TI  - Long survival with erlotinib as second line treatment in non-small cell lung
      cancer.
AB  - Male, of 69 years old, caucasian, farmer, non smoker, with hypertension,
      dyslipidemia and past pesticide exposition, without known familiar diseases. In
      October/2005, he initiated dyspnoea and asthenia for moderate efforts, cough and
      night sibling, with persisted although several antibiotic treatments were done.
      In December/2005, he went to the Emergency department, where it was seen a right
      pleural effusion. The pleural liquid study, the bronchofiberscope examination,
      the biopsy and the studies for cancer staging allowed the diagnosis: Lung
      Adenocarcinoma stage IIIB (positive pleural effusion) - December 2005. He was
      submitted to thoracocentesis, pleurodesis and local radiotherapy. He carried
      through citostatic treatment with Gemcitabine-Carboplatin from 16/02/2006 to
      13/07/2006, with some haematological toxicity. The follow up showed progression
      disease, initiating second line of treatment with Erlotinib 150mg, at 21/08/2006.
      He maintains the same treatment with disease stability and a general good
      condition, only showing a grade II rash (face, forearms and hands) as secondary
      effect of treatment. Rev Port Pneumol 2008; XIV (Supl 3): S83-S86. 

PMID- 25967692
TI  - Erlotinib in non-small cell lung cancer's second line treatment. Clinical case.
AB  - Male, of 58 years, caucasian, construction worker, non smoker, with depressive
      syndrome, biliary lithiasis, renal cysts, surgery for benign intestinal polyps
      and relevant familiar history - aunt with lung cancer and mother with colon
      cancer. He initiated thorax pain and vomitting and made a chest x-ray, showing a
      right basal lung mass. During the etiologic study, he was submitted to
      thoracotomy with biopsy, in April 2006 - "fine granulations, spread for all the
      pulmonary field", allowing the diagnosis - adenosquamous lung carcinoma, stage IV
      (16/05/2006). He initiated citostatic treatment with vinorelbine-carboplatin in
      02/06/2006, with haematological toxicity and later with neurological toxicity. At
      that time, he passed to second line treatment with erlotinib, that it was
      initiated in 11/06/2007, without significant secondary effects. Patient developed
      trigemic nerve pain, in October/2007, which subsequent study disclosed right
      esfenopetroclival meningioma, treated with radiosurgery. Later he presented
      cerebral metastization and erlotinib was discontinued in 09/06/2008. He was
      submitted to neuroradiosurgery. Now is under symptom support care. Rev Port
      Pneumol 2008; XIV (Supl 3): S79-S82. 

PMID- 25967694
TI  - Long-lasting control with erlotinib in advanced non-small cell lung cancer
      (NSCLC).
AB  - The authors present a clinical case of a caucasian male patient, 59 years-old,
      non-smoker, with an advanced non-small cell lung carcinoma (NSCLC), with 3 years
      of follow-up, received erlotinib for 18 months, after failure of more than one
      chemotherapy schedule, without evidence of oncologic progression. The patient
      evidences excellent quality of life, controlled sintomatology, recovery of the
      capacity of tolerance to the effort and it maintains his professional activities.
      The treatment with erlotinib has been well tolerated, although exhibiting grade 1
      cutaneous toxicity. Rev Port Pneumol 2008; XIV (Supl 3): S9-S15. 

PMID- 25967695
TI  - Peripheral Facial Palsy: Does Patients' Religiousness Matter for the
      Otorhinolaryngologist?
AB  - In order to deal with the suffering, a frequent strategy employed by patients is
      the use of religious beliefs and behaviors. Nevertheless, few studies in
      otorhinolaryngology have investigated this dimension. Therefore, the present
      study aims to investigate the role of religiousness on quality of life, mental
      health, self-esteem and appearance in 116 patients with peripheral facial palsy
      (PFP). A cross-sectional, single-center study was carried out between 2010 and
      2012 in PFP outpatients. We assessed socio-demographic data, PFP characteristics,
      depression, anxiety, quality of life, self-esteem, appearance and religiosity. A
      linear regression (adjusted for confounders) was performed to investigate whether
      religiosity was associated with any outcomes. The present study found that
      religious attendance, but not other types of religiousness, was related to
      quality of life and mental health on PFP patients. In addition, ENT patients
      would like their doctors to ask them about their faith and religion as part of
      their medical care. These findings give further support to the importance of
      religious and spiritual beliefs on ENT patients. Otorhinolaryngologists should be
      aware of the positive and negative aspects of religion and be prepared to address
      these issues in clinical practice. 

PMID- 25967697
TI  - Prostate involvement in granulomatosis with polyangitis: a rarity.

PMID- 25967696
TI  - Mineralocorticoid receptor blockade prevents vascular remodelling in a rodent
      model of type 2 diabetes mellitus.
AB  - Mineralocorticoid receptors (MRs), which are activated by mineralocorticoids and
      glucocorticoids, actively participate in mechanisms that affect the structure and
      function of blood vessels. Although experimental and clinical evidence shows that
      vascular damage in diabetes is associated with structural alterations in large
      and small arteries, the role of MR in this process needs further studies. Thus,
      we tested the hypothesis that MR, through redox-sensitive mechanisms, plays a
      role in diabetes-associated vascular remodelling. Male, 12-14-weeks-old db/db
      mice, a model of type 2 diabetes and their non-diabetic counterpart controls
      (db/+) were treated with spironolactone (MR antagonist, 50 mg/kg/day) or vehicle
      for 6 weeks. Spironolactone treatment did not affect blood pressure, fasting
      glucose levels or weight gain, but increased serum potassium and total
      cholesterol in both, diabetic and control mice. In addition, spironolactone
      significantly reduced serum insulin levels, but not aldosterone levels in
      diabetic mice. Insulin sensitivity, evaluated by the HOMA (homoeostatic model
      assessment)-index, was improved in spironolactone-treated diabetic mice.
      Mesenteric resistance arteries from vehicle-treated db/db mice exhibited inward
      hypertrophic remodelling, increased number of smooth muscle cells and increased
      vascular stiffness. These structural changes, determined by morphometric analysis
      and with a myography for pressurized arteries, were prevented by spironolactone
      treatment. Arteries from vehicle-treated db/db mice also exhibited augmented
      collagen content, determined by Picrosirius Red staining and Western blotting,
      increased reactive oxygen species (ROS) generation, determined by dihydroethidium
      (DHE) fluorescence, as well as increased expression of NAD(P)H oxidases 1 and 4
      and increased activity of mitogen-activated protein kinases (MAPKs).
      Spironolactone treatment prevented all these changes, indicating that MR
      importantly contributes to diabetes-associated vascular dysfunction by inducing
      oxidative stress and by increasing the activity of redox-sensitive proteins. 

PMID- 25967698
TI  - 60 YEARS OF NEUROENDOCRINOLOGY: MEMOIR: Harris' neuroendocrine revolution: of
      portal vessels and self-priming.
AB  - Geoffrey Harris, while still a medical student at Cambridge, was the first
      researcher (1937) to provide experimental proof for the then tentative view that
      the anterior pituitary gland was controlled by the CNS. The elegant studies
      carried out by Harris in the 1940s and early 1950s, alone and in collaboration
      with John Green and Dora Jacobsohn, established that this control was mediated by
      a neurohumoral mechanism that involved the transport by hypophysial portal vessel
      blood of chemical substances from the hypothalamus to the anterior pituitary
      gland. The neurohumoral control of anterior pituitary secretion was proved by the
      isolation and characterisation of the 'chemical substances' (mainly
      neuropeptides) and the finding that these substances were released into
      hypophysial portal blood in a manner consistent with their physiological
      functions. The new discipline of neuroendocrinology - the way that the brain
      controls endocrine glands and vice versa - revolutionised the treatment of
      endocrine disorders such as growth and pubertal abnormalities, infertility and
      hormone-dependent tumours, and it underpins our understanding of the sexual
      differentiation of the brain and key aspects of behaviour and mental disorder.
      Neuroendocrine principles are illustrated in this Thematic Review by way of
      Harris' major interest: hypothalamic-pituitary-gonadal control. Attention is
      focussed on the measurement of GnRH in hypophysial portal blood and the role
      played by the self-priming effect of GnRH in promoting the onset of puberty and
      enabling the oestrogen-induced surge or pulses of GnRH to trigger the ovulatory
      gonadotrophin surge in humans and other spontaneously ovulating mammals. 

PMID- 25967700
TI  - Vegetarian diets and Adventists.

PMID- 25967699
TI  - Voluntary exercise partially reverses neonatal alcohol-induced deficits in mPFC
      layer II/III dendritic morphology of male adolescent rats.
AB  - Developmental alcohol exposure in humans can produce a wide range of deficits
      collectively referred to as fetal alcohol spectrum disorders (FASD). FASD-related
      impairments in executive functioning later in life suggest long-term damage to
      the prefrontal cortex (PFC). In rodent neonates, moderate to high levels of
      alcohol exposure decreased frontal lobe brain size and altered medial PFC
      pyramidal neuron dendritic morphology. Previous research in our lab demonstrated
      that neonatal alcohol exposure decreased basilar dendritic complexity but did not
      affect spine density in Layer II/III pyramidal neurons in 26- to 30-day-old rats.
      The current study adds to the literature by evaluating the effect of neonatal
      alcohol exposure on mPFC Layer II/III basilar dendritic morphology in adolescent
      male rats. Additionally, it examines the potential for voluntary exercise to
      mitigate alcohol-induced deficits on mPFC dendritic complexity. An animal model
      of binge drinking during the third trimester of pregnancy was used. Rats were
      intubated with alcohol (alcohol-exposed, AE; 5.25 g kg(-1) day(-1)) on postnatal
      days (PD) 4-9; two control groups were included (suckle control and sham
      intubated). Rats were anesthetized and perfused with heparinized saline solution
      on PD 42, and brains were processed for Golgi-Cox staining. Developmental alcohol
      exposure decreased spine density and dendritic complexity of basilar dendrites of
      Layer II/III neurons in the medial PFC (mPFC) compared to dendrites of control
      animals. Voluntary exercise increased spine density and dendritic length in AE
      animals resulting in elimination of the differences between AE and SH rats. Thus,
      voluntary exercise during early adolescence selectively rescued alcohol-induced
      morphological deficits in the mPFC.

PMID- 25967701
TI  - The effectiveness of perindopril vs. lisinopril on reducing the incidence of
      diabetes and renal diseases: A cohort study of 20,252 patients.
AB  - BACKGROUND: Lisinopril and perindopril are two commonly used first-line
      antihypertensive agents. Few studies compared their effectiveness in reducing the
      incidence of renal diseases and diabetes. METHODS: Adult patients who received
      new prescriptions of lisinopril or perindopril from 2001 to 2005 in all public
      hospitals and clinics in Hong Kong were included, and followed up for at least 2
      years. Patients prescribed the angiotensin converting enzyme inhibitors (ACEIs)
      for <1 month were excluded. The incidence of admissions due to renal diseases and
      diabetes was evaluated. We used Cox proportional hazard regression models to
      assess hospital admissions as the outcome measures, adjusting for age, sex,
      socioeconomic status, service types, and the proportion of days covered as a
      measure of medication adherence. The regression models were constructed with
      propensity score matching to minimize indication biases. RESULTS: 20,252 eligible
      patients with an average age of 64.5 years (SD 15.0) were included. The admission
      rates 24 months within the date of index prescription due to renal diseases were
      3.1% (lisinopril) and 2.3% (perindopril); and 9.6% (lisinopril) and 7.2%
      (perindopril) for diabetes. Except for admissions due to diabetes at 6 months,
      lisinopril users were significantly more likely to be admitted due to renal
      diseases (adjusted hazard ratios: 1.304 to 1.378) and diabetes (1.146 to 1.231)
      than perindopril users at all time points. CONCLUSIONS: Patients prescribed
      different ACEIs might have a different incidence of hospital admissions. Future
      studies should be conducted to evaluate the comparative effectiveness of
      different ACEIs on various patient-centered outcomes by head-to-head randomized
      controlled trials.

PMID- 25967702
TI  - Is patient-prosthesis mismatch a predictor of survival or a surrogate marker of
      co-morbidities in cardiac surgery?
AB  - BACKGROUND: Patient-prosthesis mismatch (PPM) has ignited much debate and no
      definite conclusions have been drawn on the outcome of these patients. Therefore,
      additional large studies with long-term follow-up are required to help the
      cardiologist and surgeon outline the best therapeutic strategy for patients with
      high risk for PPM. METHODS: Patients who underwent aortic valve replacement (AVR)
      from 2000 to 2013 were identified. Baseline and operative data was extracted and
      indexed effective orifice area calculated for each patient. The presence of PPM
      was defined in those patients with an iEOA <= 0.85 cm(2)/m(2). Regression
      analyses were performed to determine the association of PPM with operative
      mortality, post-operative complications and survival. Predictors for PPM were
      evaluated based on clinical and operative data. RESULTS: From 2023 patients who
      underwent AVR, PPM was present in 64.6%. These patients had increased age, more
      coronary artery bypass procedures, increased risk of diabetes, hypertension,
      higher creatinine values and higher Euroscore. Age, body surface area, prosthesis
      type and size were found to be predictors of mismatch. Operative mortality (8.1%
      vs 5.7%, p = 0.05), stroke (3.9% vs 2.4, p = 0.02) and acute kidney injury (47.6%
      vs 35.1%, p =< 0 .001) were more frequent in patients with PPM and mean 10-year
      survival was reduced (6.6 years, 95% CI: 6.3-6.8 vs 7.3, 95% CI: 6.9-7.2, p <
      0.001). After adjusting for confounders, PPM was not found to be associated to
      either adverse outcome or survival. CONCLUSIONS: Patients with PPM have worse
      operative mortality, post-operative complications and survival mainly due to the
      fact that they represent a higher risk population based on age and co
      morbidities.

PMID- 25967703
TI  - The Gigant primary cerebral hydatid cyst with no marked manifestation: a case
      report and review of literature.
AB  - Hydatid cyst is a parasitic infestation that rarely affects the brain. A 14 year
      old child with a large mass of intracranial hydatid cysts (122 x 110 x 98 mm),
      but no symptoms except for an intermittent headache for 2 months is presented.
      Triple cysts were removed after suitable craniotomy. The literature was reviewed
      and the case was compared with the published reports.

PMID- 25967704
TI  - Evaluation of the intraocular pressure changes during micturition in patients
      with benign prostatic hyperplasia.
AB  - OBJECTIVE: To evaluate the effect of the Valsalva maneuver (VM) during
      micturition on intraocular pressure (IOP) in patients with benign prostatic
      hyperplasia (BPH). PATIENTS AND METHODS: IOP were measured before and during
      micturition in uroflowmetry testing by Tonopen-Avia (Reichert Inc., NY, USA) in
      35 eyes of 35 patients with BPH. International Prostate Symptoms Score (IPSS)
      questionnaire was used for quantification of BPH symptoms. The subjects were
      divided into two groups according to IPSS questionnaire: patients with low IPSS
      scores and patients with high IPSS scores. RESULTS: The mean IOP before and
      during micturition in patients with BPH were 15.26 +/- 4.39 mmHg and 16.23 +/-
      4.43 mmHg, respectively (p = 0.047). When patients with BPH were assigned to two
      distinct groups according to the IPSS scores, IOP did not differ in patients with
      low IPSS scores (p = 0.590), whereas mean IOP was significantly higher in
      patients with high IPSS scores (p = 0.007). CONCLUSIONS: The Valsalva maneuver,
      performed during micturition, can lead to significant IOP increase in patients
      with BPH, particularly in advanced disease.

PMID- 25967705
TI  - Analysis of laparoscopy on endometriosis patients with high expression of CA125.
AB  - OBJECTIVE: To analyze the clinical effect of laparoscopy on patients with
      endometriosis and a high expression of CA125. PATIENTS AND METHODS: One hundred
      cases of endometriosis treated in our hospital from May 2012 to August 2014 were
      selected as research subjects, after approval from the hospital and the informed
      consent of patients. The subjects were randomly divided into a control group and
      a study group with 50 cases in each group. The control group underwent the
      traditional surgery, while the research group underwent laparoscopy. The clinical
      curative effect were compared between the two groups of patients. RESULTS: The
      research group's postoperative 6h, 12h, 24h CA125 levels were compared to those
      of the control group. There was statistically significant difference between
      groups (p < 0.05). Surgery and hospitalization time, intraoperative bleeding
      volume, and and incision length index of the two groups of patients were
      compared. There were statistically significant differences between the two groups
      (p < 0.05). CONCLUSIONS: Laparoscopic surgery in endometriosis patients with high
      expression of CA125 is curative, and the patients'recovery after surgery is
      promising.

PMID- 25967706
TI  - Clinical evaluation of safety and efficacy of Boswellia-based cream for
      prevention of adjuvant radiotherapy skin damage in mammary carcinoma: a
      randomized placebo controlled trial.
AB  - OBJECTIVE: Acute radiation erythema and other skin reactions are common adverse
      effects experienced by breast carcinoma patients undergoing radiotherapy
      treatment. Boswellic acids are pentacyclic triterpenes extracted from the resins
      of the tropical tree Boswellia serrata with strong anti-inflammatory properties.
      This study was designed to evaluate the safety and the efficacy of the
      application of a base cream containing boswellic acids in a proprietary
      formulation (Bosexil(R)) for the prevention and relief of radiation-induced
      adverse effects in breast cancer patients. PATIENTS AND METHODS: The acute skin
      reactions were clinically evaluated by visual intensity and computer-assisted
      skin color analysis, and toxicity was assessed by the Radiation Therapy Oncology
      Group (RTOG) rating scale. RESULTS: These findings indicate that the use of a
      boswellia-based cream is effective in reducing the use of topical corticosteroids
      and is able to reduce the grade of erythema and the skin superficial symptoms,
      being well tolerated by the patients. CONCLUSIONS: Further studies comparing
      boswellia cream with other topical agents will be appropriate to confirm the
      effectiveness of this treatment for breast cancer patients under radiation
      therapy.

PMID- 25967707
TI  - The effect of low-nitrogen and low-calorie parenteral nutrition combined with
      enteral nutrition on inflammatory cytokines and immune functions in patients with
      gastric cancer: a double blind placebo trial.
AB  - OBJECTIVE: The aim of this study is to investigate the effect of low-nitrogen and
      low-calorie parenteral nutrition (PN) combined with enteral nutrition (EN) on the
      inflammatory cytokines and immune function in patients with gastric cancer.
      PATIENTS AND METHODS: Between May 2012 and May 2014, 90 patients undergoing
      surgery for gastric cancer in our institution were involved in this double blind
      placebo study and randomly divided into experimental group and control group, 45
      patients of each group. Patients in the control group would receive total
      parenteral nutrition (TPN) whereas patients in the experimental group would be
      supported with low-nitrogen and low-calorie PN combined with EN. RESULTS: On the
      7th postoperative day 7, levels of IgA, IgM and IgG in experimental group were
      significantly higher than those in the control group and preoperative values (p <
      0.05). CRP level was significantly lower than that of controls and preoperatively
      (p < 0.05). Levels of IL-2 and TNF-alpha were significantly higher than those of
      controls and preoperatively (p < 0.05). CONCLUSIONS: As low-nitrogen and low
      calorie PN combined with EN can effectively improve the immune function, reduce
      the inflammatory reactions and improve the postoperative quality of life (QoL)
      and prognosis in patients with gastric cancer, it is suitable for clinical
      application.

PMID- 25967709
TI  - Pathways involved in the evolution of leukemic stem cells.
AB  - Understanding the evolution of the cancer cell from a normal cell holds the key
      to developing novel, potent therapies against cancer. Two hypotheses describing
      the origins of cancer cells have been developed: one stating that any normal cell
      can acquire the ability to replicate indefinitely and evade natural cell death
      signals by accumulating multiple mutations over time, and a second suggesting
      that adult stem cells, by virtue of their pre-existing capacity for
      differentiation, asymmetric division and self-renewal, are the more likely
      targets of carcinogenic mutation. The leukemic stem cell (LSC) was the first
      cancer stem cell described. Evolving from the aberrant regulation and mutation of
      hematopoietic stem cells (HSCs), LSCs are suggested to encompass the subset of
      tumor cells sufficient for continued tumorigenesis. LSCs were also found to
      differentiate into a variety of cancer cell progenitors in a manner reminiscent
      of HSC differentiation, also explaining the observed heterogeneity of leukemic
      cells. How these cells form from HSCs remains to be fully comprehended. However,
      over recent years, marked progress has been made in contributing to our knowledge
      of cancer stem cells and what signaling cascades are involved in their
      development. Therapeutics targeting the pathways allowing for LSCs to sustain
      proliferation and self-renewal may prove to be more effective treatments for
      lymphoblastic leukemia. 

PMID- 25967708
TI  - Relationship between CD4+CD25+ Treg and expression of HIF-1alpha and Ki-67 in
      NSCLC patients.
AB  - OBJECTIVE: To investigate the relationship between the CD4+CD25+ Treg cell
      proportion in the peripheral blood and the clinicopathologic features of non
      small cell lung cancer (NSCLC) patients and hypoxia-inducible factor-1alpha (HIF
      1alpha), Ki-67 expression. PATIENTS AND METHODS: Flow cytometry was used to
      measure the CD4+CD25+ Treg cell level in peripheral blood and immunohistochemical
      staining used to detect the expression of HIF-1alpha and Ki-67 protein in cancer
      tissue of each of 50 NSCLC patients. RESULTS: The level of CD4+CD25+ Treg cell in
      peripheral blood was related to pathologic grades (t = 3.265, p = 0.006) and
      clinical stage (t = 4.417, p = 0. 001) of NSCLC instead of to patient's gender
      and pathologic type of tumor (p > 0.05). The level of CD4+CD25+ Treg cell was
      positively correlated with the expression of HIF-1alpha (r = 0.711, p = 0.003)
      and Ki-67 (r = 0.517, p = 0.04), respectively. CONCLUSIONS: CD4+CD25+ Treg cell
      can be used as a predictor of immune status and prognosis of NSCLC patients and
      the levels of HIF-1alpha and Ki-67 protein expression may relate to inhibition of
      immune cells.

PMID- 25967710
TI  - Network analysis of differentially expressed genes reveals key genes in small
      cell lung cancer.
AB  - OBJECTIVE: A combination of comparative analysis of gene expression profiles
      between normal tissue samples and small cell lung cancer (SCLC) samples and
      network analysis was performed to identify key genes in SCLC. MATERIALS AND
      METHODS: Microarray data set GSE43346 was downloaded from Gene Expression Omnibus
      (GEO), including 43 normal tissue samples and 23 clinical SCLC samples.
      Differentially expressed genes (DEGs) were screened out with t-test. Coexpression
      network and gene regulatory network were then constructed for the DEGs. GO
      enrichment analysis as well as KEGG pathway were performed with DAVID online
      tools to reveal over-represented biological processes. RESULTS: A total of 457
      DEGs were obtained in SCLC, 259 up-regulated and 198 down-regulated. Some of them
      exhibited enzyme inhibitor activity and chemokine activity. A coexpression
      network including 457 nodes was constructed, from which a functional module was
      extracted. Genes in the modules were closely related with cell cycle. Top 10
      nodes in the regulatory network were acquired and their sub-networks were
      extracted from the whole network. Genes in these sub-networks were related to
      cell cycle, apoptosis and transcription. A network comprising 43 microRNAs
      (miRNAs) and their target genes (also DEGs) were also constructed. Regulation of
      cell proliferation, cell cycle and regulation of programmed cell death were over
      represented in these genes. CONCLUSIONS: A range of DEGs were revealed in SCLC,
      which could enhance the understandings about the pathogenesis of this disease and
      provide potential molecular targets for diagnosis as well as treatment.

PMID- 25967711
TI  - Development and validation of HPLC method to determination of Methotrexate in
      children oncologic patients.
AB  - OBJECTIVE: The acute lymphocytic leukemia is a hematopoietic cancer that occurs
      predominantly in children. Methotrexate is one of the most useful drugs in cancer
      chemotherapy. The aim of the study was to develop and validate the methodology of
      high performance liquid chromatography (HPLC) with ultraviolet detection for
      methotrexate dosage and to determine its concentration in plasma samples from
      children with leukemia. PATIENTS AND METHODS: The study included patients from
      the outpatient care of pediatric oncology at the Faculty of Medicine of ABC
      carriers in treatment of leukemia. The study was conducted in chromatographic
      model Agilent 1100 with UV detector at 302 nm and by the method of ELISA
      microplate reader capable of reading absorbance at 450 nm. RESULTS: We obtained
      satisfactory results of selectivity, accuracy, linearity, limit of quantification
      (LOQ), limit of detection (LOD), precision and robustness and apply the basic
      criteria for validation as RE No. 899, of May 29, 2003 Guide validation of
      analytical and bioanalytical National Agency Health Surveillance (ANVISA).
      CONCLUSIONS: We conclude that results for linearity/concentration range,
      precision, robustness, limit of quantification and detection limits are within
      the acceptance criteria defined by ANVISA and that the developed analytical
      method is valid and feasible to be used as a tool in monitoring therapy of
      methotrexate.

PMID- 25967712
TI  - Meta-analysis of comparison between minimally invasive video-assisted
      thyroidectomy and conventional thyroidectomy.
AB  - OBJECTIVE: Comparing the minimally invasive video-assisted thyroidectomy (MIVAT)
      with conventional thyroidectomy in safety and clinical application. STUDY DESIGN:
      A systematic review of the literature and meta-analysis. MATERIALS AND METHODS:
      Randomized controlled trials comparing the MIVAT with conventional thyroidectomy
      were ascertained by methodical search using Medline, Embase, Pubmed, and The
      Cochrane Library. The trials data were extracted and statistical analyzed using
      STATA 11.0. RESULTS: Nine trials were identified. Operative time was
      significantly less with conventional thyroidectomy than with MIVAT, while MIVAT
      was associated with less pain at 24 hours postoperatively. MIVAT was associated
      with less scarring and greater cosmetic result. There were no statistically
      significant differences for the presence of transient recurrent laryngeal nerve
      palsy and the presence of transient hypoparathyroidism. CONCLUSIONS: MIVAT is a
      feasible, practical, and safe procedure with cosmetic benefit. It is a promising
      new technique for modern patients, with benefits over the established surgery.

PMID- 25967713
TI  - Role of the transient receptor potential (TRP) channel gene expressions and TRP
      melastatin (TRPM) channel gene polymorphisms in obesity-related metabolic
      syndrome.
AB  - OBJECTIVE: Metabolic syndrome (MetS) is correlated with increased cardiovascular
      risk and characterized by several factors, including visceral obesity,
      hypertension, dyslipidemia, and insulin resistance. The etiology of MetS is
      complex, and can be influenced by genetic susceptibility. The aim of this study
      was to investigate a possible association of transient receptor potential (TRP)
      channels gene expressions and TRP melastatin (TRPM) gene polymorphisms with MetS
      in a Turkish population. PATIENTS AND METHODS: A total of 142 patients with
      obesity-related MetS and 166 healthy controls with similar age and sex were
      enrolled to this study. For polymorphism studies, genomic DNA from the
      participants was analyzed by a BioMark 96.96 dynamic array system (Fluidigm,
      South San Francisco, CA, USA). For gene expression studies, mRNA from blood
      samples was extracted, and real time polymerase chain reaction on the BioMark HD
      system was performed. RESULTS: There was an increase in A allele (64.6% in
      patients vs. 49.5% in controls) and decrease in G allele frequencies (35.4% in
      patients vs. 50.5% in control, p = 0.0019) of the TRPM5 gene rs4929982
      (Arg578Gln) polymorphism. We also observed that the distribution of genotype and
      allele frequencies of the TRPM8 gene rs12472151 in MetS patients were
      significantly different from controls (p < 0.0001). Although there were marked
      decreases in TRPC1, TRPC3, TRPM2, TRPM5, TRPV4, TRPV5, TRPV6, MCOLN2 (TRPML2),
      and MCOLN3 (TRPML3) gene expressions, an augmentation was noted in TRPC6 gene
      expression. CONCLUSIONS: Genetic polymorphisms in TRPM5 and TRPM8 genes may
      modify individual susceptibility to MetS in the Turkish population. This study
      also revealed that there is a significant relationship between TRP channels gene
      expressions and MetS.

PMID- 25967714
TI  - Relation between weight loss and age after laparoscopic sleeve gastrectomy.
AB  - OBJECTIVE: As a bariatric surgery; Laparoscopic Sleeve Gastrectomy (LSG) has
      gained popularity in recent years. In our study, we aimed to investigate the
      impact of age on postoperative weight loss at one year after laparoscopic sleeve
      gastrectomy. PATIENTS AND METHODS: In our clinic between May 2011 and July 2013,
      55 patients who underwent LSG with the diagnosis of obesity were included in the
      study. Patients were divided into two groups below and over an age of 40.
      Preoperative and postoperative first year Body Mass Index (BMI), percent of Body
      Mass Index Lost (% BMIL) and Excess Body Mass Index Lost (% EBMIL) were recorded.
      RESULTS: A total of 55 patients with a mean age of 37.2 +/- 8.6 years were
      included in the study. 37 were women. Patients divided into the age below 40
      years old (group 1, n = 29) and over 40 years old (group 2, n = 26). The average
      age of the groups was 29.9 +/- 4.63 and 45.3 +/- 7.02, respectively.
      Characteristics of patients among groups were similar. The preoperative average
      BMI of groups were 49.34 +/- 5.87 kg/m2 and 49.73 +/- 5.38 kg/m2, postoperative
      first year mean BMI of groups were 30.05 +/- 5.78 kg/m2 and 36.15 +/- 6.64 kg/m2,
      respectively. Percentage loss in BMI was 19.29 +/- 3.14% and 13.58 +/- 2.96%,
      respectively; and % EBMIL was 82.95 +/- 21.88% and 56.75 +/- 15.90%,
      respectively. CONCLUSIONS: We suggest that age might be as a major determining
      factor for weight loss and patients over forty years old undergoing LSG for
      bariatric surgery should be informed about that they will have a lower weight
      lost.

PMID- 25967715
TI  - Gallstone recurrence after minimally-invasive cholecystolithotomy with
      gallbladder reservation: a follow-up of 720 cases.
AB  - OBJECTIVE: To discuss the hazards of cholecystolithiasis recrudesce after
      cholecystolithotomy with gallbladder reservation; To provide a theoretical basis
      for reducing the recurrence rate of gallstone. PATIENTS AND METHODS: The patients
      who were followed up for at least one year after minimally-invasive operation
      with gallbladder reservation because of cholecystolithiasis were selected. In
      this population, the patients with recurrence after surgery were as the case
      group, those patients with no recurrence after surgery were as the control group.
      Through collection of general data of selected cases, relevant information of
      Ultrasound Examinations of gallbladder and history data of the patients
      questionnaires were completed. Relevant factors of gallstone recurrence of
      patients, were observed through statistic analysis. Main factors go as follows:
      gender, age, nation, career, BMI, whether or not the patient had the history of
      chronic superficial gastritis, and regulation of gallbladder emptying function,
      family history, etc. The information of selected cases is complete. RESULTS AND
      CONCLUSIONS: The main hazards of cholecystolithiasis recurrence were BMI, family
      history of gallstone disease, and emptying function of gallbladder.

PMID- 25967716
TI  - Association of compartment defects in anorectal and pelvic floor dysfunction with
      female outlet obstruction constipation (OOC) by dynamic MR defecography.
AB  - OBJECTIVE: Chronic constipation affects more than 17% of the global population
      worldwide, and up to 50% of patients were outlet obstruction constipation (OOC).
      Women and the elderly are most likely to be affected, due to female-specific risk
      factors, such as menopause, parity and multiparity. The aim of our study was to
      investigate the association of compartment defects in anorectal and pelvic floor
      dysfunction with female outlet obstruction constipation (OOC) by MR defecography.
      PATIENTS AND METHODS: Fifty-six consecutive women diagnosed with outlet
      obstruction constipation from October 2009 to July 2011 were included. They were
      categorized into the following groups: anorectal disorder only group (27
      patients) and anorectal disorder plus multi-compartment pelvic disorder group (29
      patients). Relevant measurements were taken at rest, during squeezing and
      straining. RESULTS: Anismus was significantly more common in the anorectal
      disorder group compared to the multi-compartment pelvic disorder group.
      Conversely, rectocele, rectal prolapse, and descending perineum were
      significantly more common in the multi-compartment pelvic disorder group compared
      to the anorectal disorder group. Of the total 56 OOC patients, 34 (60.7%)
      exhibited anismus and 38 (67.9%) rectocele. Among the anismus patients, there
      were 8 patients (23.5%) with combined cystocele, and 6 patients (17.6%) with
      combined vaginal/cervical prolapse. Among the rectocele patients, there were 23
      patients (60.5%) with combined cystocele and 18 patients (47.4%) with combined
      vaginal/cervical prolapse. With respect to anorectal defects, 13 anismus patients
      (38.2%) were with signal posterior pelvic defects, 4 rectocele patients (10.5%)
      presented with signal posterior pelvic defects. CONCLUSIONS: Inadequate
      defecatory propulsion due to outlet obstruction constipation is often associated
      with multi-compartment pelvic floor disorders, whereas not about dyssynergic
      defecation.

PMID- 25967717
TI  - A study of RUNX3, E-cadherin and beta-catenin in CagA-positive Helicobacter
      pylori associated chronic gastritis in Saudi patients.
AB  - OBJECTIVE: H. pylori is the most important risk factor for gastric carcinoma.
      CagA-positive H. pylori is associated with an increased risk for gastric cancer
      compared with negative strains. RUNX3 is a tumor suppressor gene, which is
      related to the genesis of gastric cancer. beta-catenin is integrated with E
      cadherin in the cell membrane, and aberrant expression of the complex was
      reported in gastric carcinoma. Aim of this paper is to determine of the relation
      between RUNX3, E-cadherin and beta-catenin in chronic gastritis associated with
      cagA-positive H. pylori infection. PATIENTS AND METHODS: Retrospective study was
      done on formalin fixed paraffin embedded gastric biopsies blocks of 90 patients
      diagnosed as H. pylori associated chronic gastritis. H. pylori was detected using
      modified Giemsa stain. Nested PCR was used for detection of cagA, reverse
      transcription-PCR for detection of RUNX3 and immunohistochemistry for detection
      of E-cadherin and beta-catenin. RESULTS: Fifty percent of cases were found to be
      cagA positive. CagA was significantly associated with the intensity of
      mononuclear inflammation, the intensity of neutrophilic inflammation, the degree
      of mucosal atrophy and loss of RUNX3 but not with the density of H. pylori,
      intestinal metaplasia, E-cadherin or beta-catenin. There was significant relation
      between loss of RUNX3 and increasing density of H. pylori, intensity of
      neutrophilic inflammation, mucosal atrophy and intestinal metaplasia. RUNX3 was
      found to be significantly correlated with E-cadherin but not with beta-catenin. E
      cadherin showed decreased expression in 36.7% of biopsies while, beta-catenin was
      decreased in 33% of biopsies. CONCLUSIONS: Loss of RUNX3, E-cadherin and beta
      catenin was considered early events in the cascade of gastric carcinoma
      development. Loss of RUNX3 but neither E-cadherin nor beta-catenin was related to
      cagA positive H. pylori strains.

PMID- 25967718
TI  - New modalities of ultrasound-based intima-media thickness, arterial stiffness and
      non-coronary vascular calcifications detection to assess cardiovascular risk.
AB  - BACKGROUND: Carotid intima-media thickness (c-IMT), arterial stiffness (AS) and
      vascular calcification (VC) are now considered important new markers of
      atherosclerosis and have been associated with increased prevalence of
      cardiovascular events. An accurate, reproducible and easy detection of these
      parameters could increase the prognostic value of the traditional cardiovascular
      risk factors in many subjects at low and intermediate risk. Today, c-IMT and AS
      can be measured by ultrasound, while cardiac computed tomography is the gold
      standard to quantify coronary VC, although concern about the reproducibility of
      the former and the safety of the latter have been raised. Nevertheless, a safe
      and reliable method to quantify non-coronary (i.e., peripheral) VC has not been
      detected yet. AIM: To review the most innovative and accurate ultrasound-based
      modalities of c-IMT and AS detection and to describe a novel UltraSound-Based
      Carotid, Aortic and Lower limbs Calcification Score (USB-CALCs, simply named
      CALC), allowing to quantify peripheral calcifications. Finally, to propose a
      system for cardiovascular risk reclassification derived from the global
      evaluation of "Quality Intima-Media Thickness", "Quality Arterial Stiffness", and
      "CALC score" in addition to the Framingham score.

PMID- 25967719
TI  - Carotid free-floating thrombus in woman with meningioma: a case report and review
      of the literature.
AB  - OBJECTIVE: Several reports have previously described the coexistence of severe
      carotid artery disorders and brain tumors, in particular meningioma, mainly
      consisting of arterial occlusion or obstruction due to direct compression by
      tumor mass, with possible presence of transient neurological symptoms as well as
      complete cerebral infarction. Free-floating thrombus (FFT) is an uncommon
      condition, characterized by the presence of thrombotic material partially
      attached to the arterial wall with evidence of heartbeat associated floating. To
      our knowledge, our case represents the first report in literature about presence
      of internal carotid FFT in patient affected by meningioma. CASE REPORT: In this
      report, sharing singular images and videos of this uncommon condition, we present
      the first case of a right internal carotid artery FFT in a 59-year-old woman
      affected by meningioma, successfully treated with antiplatelet medication
      together with anticoagulation and high dose of statins. CONCLUSIONS: Our case
      confirms the possible association between carotid artery disorders and
      meningioma, involving for the first time a FFT. These findings make desirable to
      explore carotid district in patients with brain tumors, especially meningioma,
      even if symptoms suggestive of ischemic suffering are not present, in order to
      make an early diagnosis, so preventing marked ischemic events.

PMID- 25967720
TI  - Predictors of major adverse cardiovascular events; results of population based
      MELEN study with prospective follow-up.
AB  - OBJECTIVE: In healthy persons, cardiovascular risk is the result of multiple
      interacting risk associates including demographic, clinical, genetic and
      environmental factors. Several non-invasive tools such as echocardiography,
      ultrasonography and electrocardiography as well as new biochemical markers were
      shown to be applicable to predict cardiovascular events. However, implementation
      of all of these tools has not been tested before. The aim of the study was to
      evaluate the independent predictors of major adverse cardiovascular events in a
      prospective population based study, with the use of bioempedance analysis,
      echocardiography, ultrasonography and ECG. PATIENTS AND METHODS: The baseline
      measurements were conducted on 2230 participants (1427 women, 803 men with a mean
      age of 49 +/- 15). The follow-up was done 36 months after the baseline admission
      via telephone call. Major adverse event was defined as mortality or myocardial
      infarction or stroke. RESULTS: Follow-up data was possible in 1495 participants
      (65%). During the follow-up of 36 months (4485 patient years), 42 major adverse
      events occurred (0.03%). Among them, 16 were death (1 stroke, 2 cancer, 13
      cardiac related), 12 were stroke and 14 were myocardial infarction. Age, body
      mass index and atrial fibrillation were independent predictors of major adverse
      events; AF being the most powerful (Odds ratio 10.46; 95% confidence interval
      [1.73-63.14]; p = 0.010). CONCLUSIONS: Age, lower body mass index and atrial
      fibrillation were independent predictors of major cardiovascular events in our
      cohort.

PMID- 25967721
TI  - Non-extracorporeal circulation for coronary artery bypass graft surgery is more
      beneficial than extracorporeal circulation.
AB  - OBJECTIVE: The objective of this study was to compare coronary artery bypass
      graft (CABG) surgery with non-extracorporeal vs. extracorporeal circulation. The
      study outcomes included operative time, number of graft vessels, pulmonary
      infection rates, and systemic inflammatory markers. PATIENTS AND METHODS: 96
      patients received selective CABG, either with non-extracorporeal (study group; n
      = 48) or extracorporeal circulation (control group; n = 48). Operative time,
      pulmonary infection rates, and blood levels of inflammatory markers TNF-alpha, IL
      6, and IL-8 before and 4, 24, and 48 hours after the surgery were quantified.
      Graft vessels were quantified using computed tomography. RESULTS: Operative time
      was significantly shorter in study group (4.58 +/- 0.91 vs. 5.36 +/- 1.12 hours
      in control group; p < 0.05). The number of graft vessels and pulmonary infection
      rates were comparable between both techniques. However, systemic inflammatory
      markers were significantly (p < 0.05) lower in study group at 4 and, partly, 24
      hours after the surgery. CONCLUSIONS: Extracorporeal circulation prolongs
      operation and can aggravate systemic inflammatory response. Therefore, CABG with
      non-extracorporeal circulation offers more beneficial outcomes.

PMID- 25967722
TI  - Heart rate turbulence in masked hypertension and white-coat hypertension.
AB  - OBJECTIVE: To observe the heart rate turbulence (HRT) in patients with masked
      hypertension (MH), and white-coat hypertension (WCH). PATIENTS AND METHODS:
      Patients were classified on the basis of clinic and 24h ambulatory blood-pressure
      monitoring: essential hypertension (H, n = 32), masked hypertension (MH, n=26),
      white-coat hypertension (WCH, n = 29) and normotension (NT, n = 30). For each
      subject, we recorded 24 hours holter monitoring electrocardiogram, calculated the
      turbulence onset (TO) and turbulence slope (TS) and compared the differences.
      RESULTS: Compared with NT controls, the differences of TO and TS in the patients
      with EH, MH and WCH were statistically significant (p < 0.01). No significant
      differences were found between the EH, MH and WCH groups. CONCLUSIONS: The HRT in
      EH, MH and WCH patients is significantly lower, when their autonomic nerve
      function is damaged.

PMID- 25967723
TI  - Risk of pocket hematoma in patients on chronic anticoagulation with warfarin
      undergoing electrophysiological device implantation: a comparison of different
      peri-operative management strategies.
AB  - OBJECTIVE: Periprocedural management of warfarin remains challenging in patients
      requiring electrophysiological device surgery. For patients at high risk of
      thromboembolic events, guidelines recommend bridging therapy with heparin;
      however, this strategy is associated with a high risk of pocket hematoma. This
      paper systematically reviews studies appraising the risk of pocket hematoma with
      different perioperative anticoagulation strategies. METHODS: All relevant studies
      identified in MEDLINE/PubMed, The Cochrane Collaboration CENTRAL,
      clinicaltrials.org and in bibliographies of key articles. Estimates were combined
      using a fixed effects model. Heterogeneity was assessed by p values of chi2
      statistics and I2. Publication bias was assessed by visual examination of funnel
      plots and by Egger test. Fifteen studies enrolling 5911 patients met all
      inclusion criteria and were included in this review. RESULTS: Heparin bridging
      compared with no heparin was associated with increased risk of pocket hematoma
      (OR = 4.47, 95% CI 3.21-6.23, p < 0.00001), and prolonged hospital stay (9.13 +/-
      1.9 days vs. 5.11 +/- 1 .39 days, p < 0.00001). Warfarin continuation was not
      associated with increased pocket hematoma compared to warfarin discontinuation (p
      = 0.38), but was associated with reduced risk of pocket hematoma compared with
      heparin bridging (OR = 0.37, 95% CI 0.2-0.69, p = 0.002). Thromboembolic
      complications were reduced with heparin bridging vs. no heparin (0.50% vs.1.07%,
      p = 0.02), and no significant differences were reported between heparin bridging
      vs. warfarin continuation (p = 0.83). CONCLUSIONS: Heparin bridging is associated
      with a higher risk of pocket hematoma and a prolonged hospital stay.
      Perioperative continuation of warfarin reduces the occurrence of pocket hematoma
      compared with heparin bridging without any significant differences in
      thromboembolic complications.

PMID- 25967724
TI  - The neurophysiology of P 300--an integrated review.
AB  - Event-related potentials (ERPs) are very small voltages recorded from the scalp
      which originate in the brain structures in response to specific events or
      stimuli. They appear as a series of peaks and troughs interspersed in the
      Electroencephalogram (EEG) waves. The exact neural origins and neuropsychological
      meaning of the P300 are imprecisely known, even though appreciable progress has
      been made in the last 25 years. In this review, we will focus on the possible
      neural generators of this potential. Given the attention and memory operations
      associated with P300 generation, the first human studies on the neural origins of
      this ERP focused on the hippocampal formation using depth electrodes implanted to
      assess sources of epileptic foci in patients. Other lesion studies have found
      that the integrity of the temporal-parietal lobe junction is involved with either
      generation or transmission processes subsequent to hippocampal activity and
      contributes to ERP measures. These findings imply that hippocampal absence does
      not eliminate the P300, but that the temporal-parietal junction does affect its
      production. As mentioned till now, the neuroelectric events that underlie P300
      generation stem from the interaction between frontal lobe and
      hippocampal/temporal-parietal function. ERP and fMRI studies using oddball tasks
      have obtained patterns consistent with this frontal-to-temporal and parietal lobe
      activation pattern. Further support comes from magnetic resonance imaging (MRI)
      of gray matter volumes that suggest individual variation in P3a amplitude from
      distracter stimuli is correlated with frontal lobe area size, whereas P3b
      amplitude from target stimuli is correlated with parietal area size. Given
      distinct neuropsychological correlates for P3a and P3b, different
      neurotransmitters may be engaged for each constituent subcomponent under specific
      stimulus/task processing requirements. Available data suggest that
      dopaminergic/frontal processes for P3a and locus-coeruleus-norepinephrine/
      parietal activity for P3b are reasonable to propose. This dual-transmitter P300
      hypothesis is speculative but appears to account for a variety of findings and
      provides a useful framework for evaluating drug effects. 

PMID- 25967725
TI  - Comparison of low-dose spinal anesthesia and single-shot femoral block
      combination with conventional dose spinal anesthesia in outpatient arthroscopic
      meniscus repair.
AB  - OBJECTIVE: In the current prospective, randomized study, we aimed to compare the
      effects of low dose selective spinal anesthesia with 5 mg of hyperbaric
      bupivacaine and single-shot femoral nerve block combination with conventional
      dose selective spinal anesthesia in terms of intraoperative anesthesia
      characteristics, block recovery characteristics, and postoperative analgesic
      consumption. PATIENTS AND METHODS: After obtaining institutional Ethics Committee
      approval, 52 ASA I-II patients aged 25-65, undergoing arthroscopic meniscus
      repair were randomly assigned to Group S (conventional dose selective spinal
      anesthesia with 10 mg bupivacaine) and Group FS (low-dose selective spinal
      anesthesia with 5mg bupivacaine +single-shot femoral block with 0.25%
      bupivacaine). Primary endpoints were time to reach T12 sensory block level, L2
      regression, and complete motor block regression. Secondary endpoints were maximum
      sensory block level (MSBL); time to reach MSBL, time to first urination, time to
      first analgesic consumption and pain severity at the time of first mobilization.
      RESULTS: Demographic characteristics were similar in both groups (p > 0.05). MSBL
      and time to reach T12 sensory level were similar in both groups (p > 0.05). Time
      to reach L2 regression, complete motor block regression, and time to first
      micturition were significantly shorter; time to first analgesic consumption was
      significantly longer; and total analgesic consumption and severity of pain at
      time of first mobilization were significantly lower in Group FS (p < 0.05).
      CONCLUSIONS: The findings of the current study suggest that addition of single
      shot femoral block to low dose spinal anesthesia could be an alternative to
      conventional dose spinal anesthesia in outpatient arthroscopic meniscus repair.
      CLINICAL TRIALS REGISTRATION NUMBER: NCT02322372.

PMID- 25967726
TI  - Effects of taurine on contractions of human internal mammary artery: a potassium
      channel opening action.
AB  - OBJECTIVE: Taurine is an abundant amino acid that is widely distributed in human
      and animal tissues. Pharmacodynamic studies show that taurine has hypotensive and
      myocardial protective effects. Studies in isolated tissue baths show that taurine
      relaxes precontracted arteries. This study aimed to show the effects of taurine
      on human internal mammary artery (IMA) in vitro and to explain the mechanisms of
      its effects. METHODS: The response in the IMA was recorded isometrically by a
      force displacement transducer in isolated organ baths. Taurine (20, 40, 80 mM)
      was added to organ baths after precontraction with KCl (45 mM) or serotonin (5
      HT, 30 uM). Taurine-induced relaxations were also tested in the presence of the
      cyclooxygenase inhibitor indomethacin (10 uM), the nitric oxide synthase
      inhibitor L-NAME (100 uM), the large conductance Ca2+-activated K+ channel
      inhibitor tetraethylammonium (TEA, 1 mM), the ATP-sensitive K+ channel inhibitor
      glibenclamide (GLI, 10 uM), the voltage-sensitive K+ channel inhibitor 4
      aminopyridine (4-AP, 1 mM) and the inward rectifier K+ channel inhibitor barium
      chloride (BaCl2, 30 uM). RESULTS: Taurine did not affect the resting tone of IMA.
      However, it produced relaxation in the 5-HT and KCl -precontracted preparations.
      The relaxation to IMA was not affected by GLI, 4-AP, BaCl2, indomethacin and L
      NAME. But, TEA inhibited taurine -induced relaxations significantly (p < 0.05).
      CONCLUSIONS: The preincubation of IMA with taurine antagonized KCl and 5-HT
      induced contractions in a concentration dependent manner, while it did not affect
      the resting tone. The relaxations to taurine were significantly antagonized by
      pretreatment with TEA. These results suggest that mechanism of vasodilator effect
      of taurine in IMA may be the activation of large conductance Ca2+-activated K+
      channels.

PMID- 25967727
TI  - Preventive and early therapeutic effects of beta-glucan on the bleomycin-induced
      lung fibrosis in rats.
AB  - OBJECTIVE: The beta-glucans are long-chain polymers of glucose, which comprise
      the fungal cell wall, stimulate cells of the innate immune system, enhance
      disturbed epithelization, and have antioxidant effects. Oxidative stress has been
      implicated in the pathogenesis of bleomycin-induced lung fibrosis and various
      antioxidant agents have been studied for prevention and treatment of the disease.
      In this experimental animal study, we assessed effects of beta-glucan, extracted
      from barley, on the bleomycin-induced lung fibrosis, and evaluated differences of
      starting before and after bleomycin instillation. MATERIALS AND METHODS: Male
      Spraque-Dawley rats were given a single dose of bleomycin in pulmonary fibrosis
      groups. First dose of beta-glucan and NAC was given three days before the
      bleomycin injection, and at one of the other group beta-glucan was started 12
      hours after bleomycin and continued until 14th day. Fibrotic changes in lung were
      estimated by using Aschoft's criteria and measuring lung hydroxyproline content.
      RESULTS: Bleomycin induced severe pulmonary fibrosis with marked increase in
      hydroxyproline content of lung tissue and typical lung fibrosis, which was
      prevented by beta-glucan. Hydroxyproline level was significantly higher in
      bleomycin treated rats than the other groups, and its level was decreased in the
      therapeutic groups, especially in the beta-glucan post-bleomycin group fibrosis
      score, hydroxyproline and MDA levels returned to the control levels. On the other
      hand, reduced glutathione level elevated in the same group. CONCLUSIONS: The data
      suggest that beta-glucans have protective and early therapeutic effects against
      bleomycin-induced lung fibrosis in rats.

PMID- 25967728
TI  - Prevention of vascular damage with Lisosan G wheat extract: the in vitro basis
      for a clinical investigation.
AB  - Vascular damage and impairment play a crucial role in the pathogenesis of
      nonalcoholic fatty liver disease (NAFLD). Nutraceutical supplements might have a
      role in reducing vascular damage, provided that their efficacy is proven by
      controlled studies and is supported by a mechanistic rationale. Therefore, the
      use of nutraceutical supplements can have some effects also in the prevention of
      NFLD. Epidemiological evidence correlates the intake of whole grain and whole
      grain products with a reduced occurrence of vascular disease. Lisosan G is a
      powder obtained from Triticum Sativum (wheat), which is registered with the
      Italian Ministry of Health as a nutritional supplement. In vivo, Lisosan G has
      been shown to protect against cisplatin induced toxicity, and the use of this
      compound in the prevention of cirrhosis and steatosis has been recently been
      proposed thanks to its marked anti-oxidant activity. We discuss here the
      rationale for further investigation on this compound in the prevention of NAFLD.

PMID- 25967730
TI  - Regulation of redox signalling and autophagy during cardiovascular diseases-role
      of resveratrol.
AB  - Cardiovascular diseases remain one of the major health problems worldwide. The
      worldwide research against cardio-vascular diseases as well as genome wide
      association studies were successful in indentifying the loci associated with
      these prominent life threatening diseases but still a substantial amount of
      casualty remains unexplained. Over the last decade, the thorough understanding of
      molecular and biochemical mechanisms of cardiac disorders lead to the knowledge
      of various mechanisms of action of polyphenols to target inflammation during
      cardiac disorders. The present review article is focused on role of phytochemical
      resveratrol in regulation of redox signalling, autophagy and inflammation during
      cardiovascular pathology. 

PMID- 25967729
TI  - Propofol: an anesthetic possessing neuroprotective effects.
AB  - Propofol is a short-acting intravenous anaesthetic agent and widely used not only
      in operating rooms but also in the intensive care unit (ICU). Apart from its
      multiple anaesthetic advantages, the neuroprotective effect of propofol has been
      demonstrated in diverse models of neuronal injury. The effect of propofol results
      from activation of gamma-aminobutyric acid (GABA) receptor, modulation excitatory
      amino acid transmitter system and protecting brain cells against oxidative
      stress. Moreover, propofol is able to supress apoptosis and inflammation and to
      regulate neuroprotection-associated proteins or ion homeostasis to act its
      neuroprotective effects. This review focuses on the research progress of the
      neuroprotective effects of propofol and its mechanisms of action to date. The
      implications for possible use for the clinical setting are also discussed.

PMID- 25967731
TI  - Hydrogen sulfide releasing naproxen offers better anti-inflammatory and
      chondroprotective effect relative to naproxen in a rat model of zymosan induced
      arthritis.
AB  - OBJECTIVE: Hydrogen sulfide (H2S) is rapidly gaining ground as a physiological
      mediator of inflammation, but there is no clear consensus as to its precise role
      in inflammation. Therefore, this study was undertaken to evaluate the effects of
      ATB-346 as a novel H2S-releasing naproxen compared to naproxen, as a traditional
      non-steroidal anti-inflammatory drug on zymosan induced mono-arthritis in rats.
      MATERIALS AND METHODS: Male Wistar rats (n=48) were randomly assigned to four
      main groups: normal control, untreated arthritis, Naproxen and ATB-346 treated
      groups. Mono-arthritis was induced by intra-articular injection of zymosan into
      the knee joints. Mechanical hypernociception and joint swelling were evaluated at
      6 hours and 5 days. Inflammatory cellular recruitment and adherence, tumor
      necrosis factor alpha, nuclear factor kappa beta, total sulfide levels, and
      histological changes were evaluated in knee lavages, blood or joint tissues at
      selected time points. RESULTS: Zymosan injection evoked knee inflammation and
      pain as characterized by mechanical hypernociception, impaired gait, joint
      swelling with inflammatory exudation and histological changes. Treatment with ATB
      346 attenuated nociceptive responses, inflammatory cellular and biochemical
      changes in comparison to naproxen. Only ATB-346 was able to suppress neutrophil
      adherence and to preserve normal articular structure. CONCLUSIONS: H2S releasing
      naproxen represents an advancement over the parent drug, naproxen. Apart from the
      superior anti-inflammatory and anti-noceiceptive activity, ATB-346 offered a
      distinguished chondroprotective effect and is almost devoid from naproxen
      deleterious effects on articular cartilage.

PMID- 25967732
TI  - Retraction. Expression of RASSF1A in epithelial ovarian cancers.

PMID- 25967733
TI  - Investigation of cyano-bridged coordination nanoparticles Gd(3+)/[Fe(CN)6](3-)/D
      mannitol as T1-weighted MRI contrast agents.
AB  - Cyano-bridged Gd(3+)/[Fe(CN)6](3-) coordination polymer nanoparticles of 3-4 nm
      stabilized with D-mannitol presenting a high r1 relaxivity value of 11.4 mM(-1)
      s(-1) were investigated in vivo as contrast agents (CA) for Magnetic Resonance
      Imaging (MRI). They allow an increase of the MR image contrast and can act as an
      efficient intravascular T1 CA with a relatively long blood-circulation lifetime
      (60 min) without specific toxicity.

PMID- 25967735
TI  - Vitamin K1 distribution following intravenous vitamin K1-fat emulsion
      administration in rats.
AB  - This study investigated vitamin K1 (VK1 ) distribution following intravenous
      vitamin K1-fat emulsion (VK1 -FE) administration and compared it with that after
      VK1 injection. Rats were intravenously injected with VK1-FE or VK1 . The organ
      and tissue VK1 concentrations were determined using high-performance liquid
      chromatography method at 0.5, 2 and 4 h to determine distribution, equilibrium
      and elimination phases, respectively. In the VK1-FE group, the plasma, heart and
      spleen VK1 concentrations decreased over time. However, other organs like liver,
      lung, kidney, muscle and testis, reached peak VK1 concentrations at 2 h. In the
      VK1 injection group, the liver VK1 concentrations were significantly higher than
      those in other organs at the three time points. However, VK1 concentrations in
      the other organs peaked at 2 h. In addition, in VK1-FE group, the heart, spleen
      and lung VK1 concentrations were significantly higher than those in the VK1
      injection group at the three time points, and the liver VK1 concentration was
      significantly higher than that in the VK1 injection group at 4 h. The VK1 amount
      was greatest in the liver compared with the other organs. Thus, the liver is the
      primary organ for VK1 distribution. The distribution of VK1 is more rapid when
      injected as VK1-FE than as VK1 .

PMID- 25967734
TI  - Oxidative DNA damage is involved in cigarette smoke-induced lung injury in rats.
AB  - OBJECTIVE: Reactive oxygen species (ROS) induced by exogenous toxicants are
      suggested to be involved in carcinogenesis by oxidative modification of DNA. 8
      Hydroxyl-2-deoxyguanosine (8-OHdG) has been considered as a reliable biomarker
      for oxidative DNA damage both in vivo and in vitro studies. But the effect of
      smoking on oxidative damage has not yet been fully elucidated. METHODS: Wistar
      rats were exposed to cigarette smoke at concentrations of 20 and 60 % for 30 min,
      twice/day for 45 weeks. Then the histopathology of lung tissues, levels of ROS, 8
      OHdG, and total antioxidant (T-AOC), expression of DNA repair enzymes, e.g. 8
      oxyguaine DNA glycosylase (OGG1), and MutThomolog 1 (Oxidized Purine Nucleoside
      Triphosphatase, MTH1) were determined in urine, peripheral blood lymphocytes, and
      lung tissue. RESULTS: The results showed that long-term cigarette smoke exposure
      can cause obvious damages of lung tissue in rats. In addition, a significant and
      cigarette smoke concentration-dependent increase in ROS and 8-OHdG were observed
      compared with the non-exposed control rats. In contrast, the expression of OGG1
      and MTH1, and T-AOC levels were obviously decreased after long-term exposure to
      cigarette smoke. CONCLUSION: These findings indicate that long-term exposure to
      cigarette smoker increases ROS levels, decreases total antioxidant capacity, and
      interferes DNA repair capacity that eventually induces oxidative DNA damage,
      which appears to play an important role in cigarette smoke-induced lung injury in
      rats, and determination of 8-OHdG levels might be a useful method for monitoring
      oxidative damage in cigarette smokers.

PMID- 25967736
TI  - High-Speed Imaging Analysis of Register Transitions in Classically and Jazz
      Trained Male Voices.
AB  - BACKGROUND: Little data are available concerning register functions in different
      styles of singing such as classically or jazz-trained voices. Differences between
      registers seem to be much more audible in jazz singing than classical singing,
      and so we hypothesized that classically trained singers exhibit a smoother
      register transition, stemming from more regular vocal fold oscillation patterns.
      METHODS: High-speed digital imaging (HSDI) was used for 19 male singers (10 jazz
      trained singers, 9 classically trained) who performed a glissando from modal to
      falsetto register across the register transition. Vocal fold oscillation patterns
      were analyzed in terms of different parameters of regularity such as relative
      average perturbation (RAP), correlation dimension (D2) and shimmer. RESULTS: HSDI
      observations showed more regular vocal fold oscillation patterns during the
      register transition for the classically trained singers. Additionally, the RAP
      and D2 values were generally lower and more consistent for the classically
      trained singers compared to the jazz singers. However, intergroup comparisons
      showed no statistically significant differences. CONCLUSION: Some of our results
      may support the hypothesis that classically trained singers exhibit a smoother
      register transition from modal to falsetto register.

PMID- 25967737
TI  - Central venous-to-arterial carbon dioxide difference as a prognostic tool in high
      risk surgical patients.
AB  - INTRODUCTION: The purpose of this study was to evaluate the clinical relevance of
      high values of central venous-to-arterial carbon dioxide difference (PCO2 gap) in
      high-risk surgical patients admitted to a postoperative ICU. We hypothesized that
      PCO2 gap could serve as a useful tool to identify patients still requiring
      hemodynamic optimization at ICU admission. METHODS: One hundred and fifteen
      patients were included in this prospective single-center observational study
      during a 1-year period. High-risk surgical inclusion criteria were adapted from
      Schoemaker and colleagues. Demographic and biological data, PCO2 gap, central
      venous oxygen saturation, lactate level and postoperative complications were
      recorded for all patients at ICU admission, and 6 hours and 12 hours after
      admission. RESULTS: A total of 78 (68%) patients developed postoperative
      complications, of whom 54 (47%) developed organ failure. From admission to 12
      hours after admission, there was a significant difference in mean PCO2 gap (8.7
      +/- 2.8 mmHg versus 5.1 +/- 2.6 mmHg; P = 0.001) and median lactate values (1.54
      (1.1-3.2) mmol/l versus 1.06 (0.8-1.8) mmol/l; P = 0.003) between patients who
      developed postoperative complications and those who did not. These differences
      were maximal at admission to the ICU. At ICU admission, the area under the
      receiver operating characteristic curve for occurrence of postoperative
      complications was 0.86 for the PCO2 gap compared to Sequential Organ Failure
      Assessment score (0.82), Simplified Acute Physiology Score II score (0.67), and
      lactate level (0.67). The threshold value for PCO2 gap was 5.8 mmHg. Multivariate
      analysis showed that only a high PCO2 gap and a high Sequential Organ Failure
      Assessment score were independently associated with the occurrence of
      postoperative complications. A high PCO2 gap (>=6 mmHg) was associated with more
      organ failure, an increase in duration of mechanical ventilation and length of
      hospital stay. CONCLUSION: A high PCO2 gap at admission in the postoperative ICU
      was significantly associated with increased postoperative complications in high
      risk surgical patients. If the increase in PCO2 gap is secondary to tissue
      hypoperfusion then the PCO2 gap might be a useful tool complementary to central
      venous oxygen saturation as a therapeutic target.

PMID- 25967739
TI  - Thioimidazoline based compounds reverse glucocorticoid resistance in human acute
      lymphoblastic leukemia xenografts.
AB  - Glucocorticoids form a critical component of chemotherapy regimens for pediatric
      acute lymphoblastic leukemia (ALL) and the initial response to glucocorticoid
      therapy is a major prognostic factor, where resistance is predictive of poor
      outcome. A high-throughput screen identified four thioimidazoline-containing
      compounds that reversed dexamethasone resistance in an ALL xenograft derived from
      a chemoresistant pediatric ALL. The lead compound (1) was synergistic when used
      in combination with the glucocorticoids, dexamethasone or prednisolone. Synergy
      was observed in a range of dexamethasone-resistant xenografts representative of B
      cell precursor ALL (BCP-ALL) and T-cell ALL. We describe here the synthesis of
      twenty compounds and biological evaluation of thirty two molecules that explore
      the structure-activity relationships (SAR) of this novel class of glucocorticoid
      sensitizing compounds. SAR analysis has identified that the most effective
      dexamethasone sensitizers contain a thioimidazoline acetamide substructure with a
      large hydrophobic moiety on the acetamide. 

PMID- 25967738
TI  - Lead decreases cell survival, proliferation, and neuronal differentiation of
      primary cultured adult neural precursor cells through activation of the JNK and
      p38 MAP kinases.
AB  - Adult hippocampal neurogenesis is the process whereby adult neural precursor
      cells (aNPCs) in the subgranular zone (SGZ) of the dentate gyrus (DG) generate
      adult-born, functional neurons in the hippocampus. This process is modulated by
      various extracellular and intracellular stimuli, and the adult-born neurons have
      been implicated in hippocampus-dependent learning and memory. However, studies on
      how neurotoxic agents affect this process and the underlying mechanisms are
      limited. The goal of this study was to determine whether lead, a heavy metal,
      directly impairs critical processes in adult neurogenesis and to characterize the
      underlying signaling pathways using primary cultured SGZ-aNPCs isolated from
      adult mice. We report here that lead significantly increases apoptosis and
      inhibits proliferation in SGZ-aNPCs. In addition, lead significantly impairs
      spontaneous neuronal differentiation and maturation. Furthermore, we found that
      activation of the c-Jun NH2-terminal kinase (JNK) and p38 mitogen activated
      protein (MAP) kinase signaling pathways are important for lead cytotoxicity. Our
      data suggest that lead can directly act on adult neural stem cells and impair
      critical processes in adult hippocampal neurogenesis, which may contribute to its
      neurotoxicity and adverse effects on cognition in adults. 

PMID- 25967741
TI  - The Fourth International Meeting of ISEV, ISEV2015.

PMID- 25967740
TI  - Treatment with infliximab or azathioprine negatively impact the efficacy of
      hepatitis B vaccine in inflammatory bowel disease patients.
AB  - BACKGROUND AND AIM: Immunization against hepatitis B virus (HBV) infection is
      recommended in patients with inflammatory bowel disease (IBD), particularly in
      those under immunosuppressive therapy. Limited data are available about IBD
      patient's response to HBV vaccination. We assessed the response rate to HBV
      vaccination in IBD patients and evaluated the impact of different factors on the
      efficacy of HBV vaccination. METHODS: Anti-HBs titers were measured in a cohort
      of IBD patients under treatment with infliximab and/or azathioprine. Vaccination
      was considered efficient when anti-HBs titers were higher than 10 IU/L. RESULTS:
      We have identified 217 patients with IBD under infliximab who were vaccinated for
      hepatitis B, 172 (79%) with Crohn's Disease and the remaining with ulcerative
      colitis; 114 patients (53%) were male and mean age was 33 +/- 11 years. Overall,
      HBV vaccine was successful in 164 (76%) patients. Only 14 patients were
      vaccinated after infliximab was initiated, and only two of them had antibody
      levels above 10 IU/L. Among the patients that received vaccination before the
      beginning of infliximab, 88% of those who were vaccinated before starting
      azathioprine developed antibodies in contrast to 55% who already were under
      azathioprine. In multivariable analysis, treatment with infliximab (adjusted OR
      [95% CI]: 17.642 [8.514-33.937]) and with azathioprine (adjusted OR [95% CI]:
      3.344 [1.653-9.145]) were the only factors associated with weaker response to HBV
      vaccination. CONCLUSION: The response rate to the standard HBV vaccination in IBD
      patients is low mainly in those treated with infliximab and/or azathioprine.

PMID- 25967744
TI  - Diversity of genetic backgrounds modulating the durability of a major resistance
      gene. Analysis of a core collection of pepper landraces resistant to Potato virus
      Y.
AB  - The evolution of resistance-breaking capacity in pathogen populations has been
      shown to depend on the plant genetic background surrounding the resistance genes.
      We evaluated a core collection of pepper (Capsicum annuum) landraces,
      representing the worldwide genetic diversity, for its ability to modulate the
      breakdown frequency by Potato virus Y of major resistance alleles at the pvr2
      locus encoding the eukaryotic initiation factor 4E (eIF4E). Depending on the
      pepper landrace, the breakdown frequency of a given resistance allele varied from
      0% to 52.5%, attesting to their diversity and the availability of genetic
      backgrounds favourable to resistance durability in the plant germplasm. The
      mutations in the virus genome involved in resistance breakdown also differed
      between plant genotypes, indicating differential selection effects exerted on the
      virus population by the different genetic backgrounds. The breakdown frequency
      was positively correlated with the level of virus accumulation, confirming the
      impact of quantitative resistance loci on resistance durability. Among these
      loci, pvr6, encoding an isoform of eIF4E, was associated with a major effect on
      virus accumulation and on the breakdown frequency of the pvr2-mediated
      resistance. This exploration of plant genetic diversity delivered new resources
      for the control of pathogen evolution and the increase in resistance durability. 

PMID- 25967743
TI  - Thioamides in the collagen triple helix.
AB  - To probe noncovalent interactions within the collagen triple helix, backbone
      amides were replaced with a thioamide isostere. This subtle substitution is the
      first in the collagen backbone that does not compromise thermostability. A triple
      helix with a thioamide as a hydrogen bond donor was found to be more stable than
      triple helices assembled from isomeric thiopeptides. 

PMID- 25967745
TI  - Magnetic and magnetocaloric properties of an unusual family of carbonate-panelled
      [Ln(III)(6)Zn(III)(2)] cages.
AB  - The reaction of the pro-ligand H4L, which combines the complementary phenolic
      oxime and diethanolamine moieties within the same organic framework, with
      Zn(NO3)2.6H2O and Ln(NO3)3.6H2O in a basic methanolic solution generates a family
      of isostructural heterometallic coordination compounds of general formula
      [Ln6Zn2(CO3)5(OH)(H2L)4(H3L)2(H4L)]NO3.xMeOH [Ln = Gd, x = 30 (), Ln = Dy, x = 32
      (), Ln = Sm, x = 31 (), Ln = Eu, x = 29 (), Ln = Tb, x = 30 ()]. The octametallic
      skeleton of the cage describes a heavily distorted [Gd] octahedron capped on two
      faces by Zn(II) ions. The metal core is stabilised by a series of MU3- and MU4
      CO3(2-) ions, originating from the serendipitous fixation of atmospheric CO2. The
      magnetic properties of all family members were examined via SQUID magnetometry,
      with the chiMT product and VTVB data of the Gd analogue () being independently
      fitted by numerical diagonalisation to afford the same best-fit parameter JGd-Gd
      = -0.004 cm(-1). The MCE of complex was elucidated from specific heat data, with
      the magnetic entropy change reaching a value of 22.6 J kg(-1) K(-1) at T = 1.7 K,
      close to the maximum entropy value per mole expected from six Gd(III) spins (SGd
      = 7/2), 23.7 J kg(-1) K(-1). 

PMID- 25967742
TI  - Evidence of what works to support and sustain care at home for people with
      dementia: a literature review with a systematic approach.
AB  - BACKGROUND: This paper synthesises research evidence about the effectiveness of
      services intended to support and sustain people with dementia to live at home,
      including supporting carers. The review was commissioned to support an inspection
      regime and identifies the current state of scientific knowledge regarding
      appropriate and effective services in relation to a set of key outcomes derived
      from Scottish policy, inspection practice and standards. However, emphases on
      care at home and reduction in the use of institutional long term care are common
      to many international policy contexts and welfare regimes. METHODS: Systematic
      searches of relevant electronic bibliographic databases crossing medical,
      psychological and social scientific literatures (CINAHL, IngentaConnect, Medline,
      ProQuest, PsychINFO and Web of Science) in November 2012 were followed by
      structured review and full-text evaluation processes, the latter using
      methodology-appropriate quality assessment criteria drawing on established
      protocols. RESULTS: Of 131 publications evaluated, 56 were assessed to be of
      'high' quality, 62 of 'medium' quality and 13 of 'low' quality. Evaluations
      identified weaknesses in many published accounts of research, including lack of
      methodological detail and failure to evidence conclusions. Thematic analysis
      revealed multiple gaps in the evidence base, including in relation to take-up and
      use of self-directed support by people with dementia, use of rapid response teams
      and other multidisciplinary approaches, use of technology to support community
      dwelling people with dementia, and support for people without access to unpaid or
      informal support. CONCLUSIONS: In many areas, policy and practice developments
      are proceeding on a limited evidence base. Key issues affecting substantial
      numbers of existing studies include: poorly designed and overly narrowly focused
      studies; variability and uncertainty in outcome measurement; lack of focus on the
      perspectives of people with dementia and supporters; and failure to understanding
      the complexities of living with dementia, and of the kinds of multifactorial
      interventions needed to provide holistic and effective support. Weaknesses in the
      evidence base present challenges both to practitioners looking for guidance on
      how best to design and deliver evidence-based services to support people living
      with dementia in the community and their carers and to those charged with the
      inspection of services.

PMID- 25967746
TI  - MET/HGF pathway in multiple myeloma: from diagnosis to targeted therapy?
AB  - The interaction between neoplastic cells and the microenvironment is critical in
      several cancers and plays a central role in multiple myeloma. Microenvironmental
      stimuli support plasma cell proliferation, survival, motility and can determine
      drug resistance. The network between plasma cells and surrounding cells is also
      responsible for increasing angiogenesis, unbalancing bone formation and bony
      lesions. The MET/HGF pathway is a key player in this interaction and has been
      found to be abnormally active in both malignant plasma cells and surrounding
      cells. Patients with abnormal MET and/or HGF levels usually have a poor outcome
      even when treated with novel drugs. This review addresses the role of MET/HGF in
      the pathogenesis of myeloma and describes the role of MET/HGF signaling as a
      prognostic factor. The different techniques to detect MET/HGF abnormalities are
      examined and a description of compounds targeting MET/HGF is also provided. 

PMID- 25967747
TI  - Mask-triggered thrust reversal in the negative compatibility effect.
AB  - Rapid motor responses to visual stimuli can involve both the activation and
      inhibition of motor responses. Here, we trace the early processing dynamics of
      response generation, examining whether activation and inhibition events form a
      strict sequence when elicited by sequential stimuli, as we would expect if motor
      events are driven by fast, stimulus-triggered feedforward sweeps. We employed
      identical stimuli in two complementary paradigms. In response priming, responses
      to a target stimulus are speeded or slowed by a masked prime triggering the same
      or an alternative response, respectively. By prolonging the prime-target
      interval, the response-priming effect can reverse to form the negative
      compatibility effect (NCE), especially when the mask contains response-relevant
      features. We report two experiments in which primed pointing movements going in
      ten possible directions were measured with response-relevant, response
      irrelevant, or no masks interleaved between the primes and targets, while
      selective visual attention was varied. We showed that in response priming,
      initial responses are controlled exclusively by the prime. In the NCE, however,
      even the earliest movement phase is controlled jointly by the prime, mask, and
      target information, and a massive force in counterdirection to the primed
      response reverses the priming effects specifically for slow responses. We
      conclude that response priming reflects a strict sequence of feedforward response
      activations, whereas the activation/inhibition events in the NCE are not strictly
      serial, but integrate information from the different stimuli over time. Even
      though the mask features and visual attention modulate the NCE, its major source
      is a mask-induced, direction-specific thrust reversal of the initial response. 

PMID- 25967748
TI  - Reply: To PMID 25459556.

PMID- 25967749
TI  - Reply: To PMID 24813174.

PMID- 25967750
TI  - Reply: To PMID 8600700.

PMID- 25967751
TI  - Reply: To PMID 25130937.

PMID- 25967752
TI  - Further evidence for an association between LCI and FEV1 in patients with PCD.

PMID- 25967753
TI  - Outcome of surgery versus radiotherapy after induction treatment in patients with
      N2 disease: systematic review and meta-analysis of randomised trials.
AB  - OBJECTIVE: Chemoradiotherapy is often considered the 'standard of care' for
      patients with N2 disease. The aim was to evaluate survival outcomes of patients
      with N2 disease in multimodality trials of chemotherapy, radiotherapy and
      surgery. METHODS: Systematic review and meta-analyses (random and fixed effects)
      were performed. Searches of Medline and Embase (1980-2013) were conducted.
      Abstracts from thoracic scientific meetings were searched. Reference lists of all
      relevant studies were reviewed. All studies of patients with N2 disease who
      received induction chemotherapy or chemoradiotherapy and randomised to surgery or
      radiotherapy were included. No language restrictions were imposed. The main
      outcome was overall survival. RESULTS: 805 publications were identified. 519 and
      281 were excluded because they were not primary results from randomised trials
      (or did not include N2 disease) or did not compare surgery with radiotherapy,
      respectively. The final six trials consisted of 868 patients. In four trials,
      patients received induction chemotherapy and in two trials patients received
      induction chemoradiotherapy. The HR comparing patients randomised to surgery
      after chemotherapy was 1.01 (95% CI 0.82 to 1.23; p=0.954) whereas for patients
      randomised to surgery after chemoradiotherapy was 0.87 (0.75 to 1.01; p=0.068).
      The overall HR of all pooled trials was 0.92 (0.81 to 1.03; p=0.157).
      CONCLUSIONS: Surgery should be considered as part of multimodality treatment for
      patients with resectable lung cancer and ipsilateral mediastinal nodal disease.
      In trials where patients received surgery as part of trimodality treatment,
      overall survival was better than chemoradiotherapy alone.

PMID- 25967755
TI  - Relationships between parenting self-efficacy and distress in parents who have
      school-aged children and have been treated with hematopoietic stem cell
      transplant or have no cancer history.
AB  - OBJECTIVE: Studies demonstrate that parents with cancer experience distress and
      that parenting self-efficacy (PSE) is related to distress among parents without
      cancer. However, no study to date has examined the relationships between PSE and
      psychological distress among parents with cancer. This study sought to address
      this issue by comparing parents with cancer who had undergone hematopoietic stem
      cell transplantation (HSCT) to parents without cancer on measures of PSE and
      psychological distress. METHODS: A sample of 57 patients diagnosed with cancer
      who had undergone HSCT and a control group of 57 parents with no history of
      cancer were recruited for participation in the study. Medical record reviews
      assessed clinical variables, and participants filled out self-report measures of
      demographics, PSE, general self-efficacy, and psychological distress. RESULTS: As
      hypothesized, parents with cancer reported less PSE and more psychological
      distress than controls (all p-values <= 0.05). Furthermore, findings indicated
      that both PSE and general self-efficacy mediated the relationship between cancer
      status and psychological distress. CONCLUSIONS: Findings expand understanding of
      the potential sources of distress among parents with cancer who have been treated
      with HSCT and who have school-aged children. They also suggest that interventions
      aimed at reducing distress in these individuals should seek to target both
      parenting and general self-efficacy.

PMID- 25967754
TI  - Dorsal Cochlear Nucleus of the Rat: Representation of Complex Sounds in Ears
      Damaged by Acoustic Trauma.
AB  - Acoustic trauma damages the cochlea but secondarily modifies circuits of the
      central auditory system. Changes include decreases in inhibitory neurotransmitter
      systems, degeneration and rewiring of synaptic circuits, and changes in neural
      activity. Little is known about the consequences of these changes for the
      representation of complex sounds. Here, we show data from the dorsal cochlear
      nucleus (DCN) of rats with a moderate high-frequency hearing loss following
      acoustic trauma. Single-neuron recording was used to estimate the organization of
      neurons' receptive fields, the balance of inhibition and excitation, and the
      representation of the spectra of complex broadband stimuli. The complex stimuli
      had random spectral shapes (RSSs), and the responses were fit with a model that
      allows the quality of the representation and its degree of linearity to be
      estimated. Tone response maps of DCN neurons in rat are like those in other
      species investigated previously, suggesting the same general organization of this
      nucleus. Following acoustic trauma, abnormal response types appeared. These can
      be interpreted as reflecting degraded tuning in auditory nerve fibers plus loss
      of inhibitory inputs in DCN. Abnormal types are somewhat more prevalent at later
      times (103-376 days) following the exposure, but not significantly so. Inhibition
      became weaker in post-trauma neurons that retained inhibitory responses but also
      disappeared in many neurons. The quality of the representation of spectral shape,
      measured by sensitivity to the spectral shapes of RSS stimuli, was decreased
      following trauma; in fact, neurons with abnormal response types responded mainly
      to overall stimulus level, and not spectral shape.

PMID- 25967756
TI  - Determining Pre-Conception Risk Profiles Using a National Online Self-Reported
      Risk Assessment: A Cross-Sectional Study.
AB  - AIM: To measure the prevalence of health risk factors in women who are preparing
      for pregnancy, using an online publicly available questionnaire aimed at
      identifying personal and pre-conception risks and at providing tailored
      information. METHODS: A nation-wide available, free, web-based, self-reported
      questionnaire for pre-conception use (in Dutch). Between May 2006 and August
      2009, 89,946 questionnaires were completed (78,732 were from unique respondents)
      and available for research purposes, from which those of non-pregnant women (n =
      66,617) were selected. Socio-demographic subgroups were distinguished by age,
      ethnicity, urban living area and living in a deprived neighbourhood. The four pre
      conception risk domains were lifestyle, medical, reproductive and family history;
      together they were defining the risk profile. chi(2) tests were used to compare
      the risk profiles among the subgroups. RESULTS: The prevalences of the reported
      risk factors are given. The risk factor profiles revealed that the average,
      responding, non-pregnant, Dutch woman is exposed to a substantial number of risk
      factors. Different risk profiles were observed in the different socio-demographic
      subgroups. Women older than 36 years, of non-Western origin, living in urban
      areas and those in deprived neighbourhoods showed higher risk profiles, based on
      a larger number of risks, with significantly higher prevalences. CONCLUSION: Self
      reported data from a large, self-selected, non-pregnant population who actively
      visited a web-site for reproductive information suggest the need for active
      general pre-conception care as risk factors were abundant. A considerable
      increase in attention for pre-conception care is justified; different
      subpopulations most likely require adapted approaches.

PMID- 25967758
TI  - Clinical and Psychometric Evaluations of the Cerebral Vision Screening
      Questionnaire in 461 Nonaphasic Individuals Poststroke.
AB  - BACKGROUND: Cerebral vision disorders (CVDs) are frequent after brain damage and
      impair the patient's outcome. Yet clinically and psychometrically validated
      procedures for the anamnesis of CVD are lacking. OBJECTIVE: To evaluate the
      clinical validity and psychometric qualities of the Cerebral Vision Screening
      Questionnaire (CVSQ) for the anamnesis of CVD in individuals poststroke. METHODS:
      Analysis of the patients' subjective visual complaints in the 10-item CVSQ in
      relation to objective visual perimetry, tests of reading, visual scanning, visual
      acuity, spatial contrast sensitivity, light/dark adaptation, and visual depth
      judgments. Psychometric analyses of concurrent validity, specificity,
      sensitivity, positive/negative predictive value, and interrater reliability were
      also done. RESULTS: Four hundred sixty-one patients with unilateral (39.5% left,
      47.5% right) or bilateral stroke (13.0%) were included. Most patients were
      assessed in the chronic stage, on average 36.7 (range = 1-620) weeks poststroke.
      The majority of all patients (96.4%) recognized their visual symptoms within 1
      week poststroke when asked for specifically. Mean concurrent validity of the CVSQ
      with objective tests was 0.64 (0.54-0.79, P < .05). The mean positive predictive
      value was 80.1%, mean negative predictive value 82.9%, mean specificity 81.7%,
      and mean sensitivity 79.8%. The mean interrater reliability was 0.76 for a 1-week
      interval between both assessments (all P < .05). CONCLUSION: The CVSQ is suitable
      for the anamnesis of CVD poststroke because of its brevity (10 minute), clinical
      validity, and good psychometric qualities. It, thus, improves neurovisual
      diagnosis and guides the clinician in the selection of necessary assessments and
      appropriate neurovisual therapies for the patient.

PMID- 25967757
TI  - The Effect of Lesion Size on the Organization of the Ipsilesional and
      Contralesional Motor Cortex.
AB  - Recovery of hand function following lesions in the primary motor cortex (M1) is
      associated with a reorganization of premotor areas in the ipsilesional
      hemisphere, and this reorganization depends on the size of the lesion. It is not
      clear how lesion size affects motor representations in the contralesional
      hemisphere and how the effects in the 2 hemispheres compare. Our goal was to
      study how lesion size affects motor representations in the ipsilesional and
      contralesional hemispheres. In rats, we induced lesions of different sizes in the
      caudal forelimb area (CFA), the equivalent of M1. The effective lesion volume in
      each animal was quantified histologically. Behavioral recovery was evaluated with
      the Montoya Staircase task for 28 days after the lesion. Then, the organization
      of the CFA and the rostral forelimb area (RFA)--the putative premotor area in
      rats--in the 2 cerebral hemispheres was studied with intracortical
      microstimulation mapping techniques. The distal forelimb representation in the
      RFA of both the ipsilesional and contralesional hemispheres was positively
      correlated with the size of the lesion. In contrast, lesion size had no effect on
      the contralesional CFA, and there was no relationship between movement
      representations in the 2 hemispheres. Finally, only the contralesional RFA was
      negatively correlated with chronic motor deficits of the paretic forelimb. Our
      data show that lesion size has comparable effects on motor representations in
      premotor areas of both hemispheres and suggest that the contralesional premotor
      cortex may play a greater role in the recovery of the paretic forelimb following
      large lesions.

PMID- 25967759
TI  - Noninvasive Neuromodulation in Poststroke Gait Disorders: Rationale, Feasibility,
      and State of the Art.
AB  - Walking rehabilitation is one of the primary goals in stroke survivors because of
      its great potential for recovery and its functional relevance in daily living
      activities. Although 70% to 80% of people in the chronic poststroke phases are
      able to walk, impairment of gait often persists, involving speed, endurance, and
      stability. Walking involves several brain regions, such as the sensorimotor
      cortex, supplementary motor area, cerebellum, and brainstem, which are
      approachable by the application of noninvasive brain stimulation (NIBS). NIBS
      techniques, such as repetitive transcranial magnetic stimulation and transcranial
      direct current stimulation, have been reported to modulate neural activity beyond
      the period of stimulation, facilitating neuroplasticity. NIBS methods have been
      largely applied for improving paretic hand motor function and stroke-associated
      cognitive deficits. Recent studies suggest a possible effectiveness of these
      techniques also in the recovery of poststroke gait disturbance. This article is a
      selective review about functional investigations addressing the mechanisms of
      lower-limb motor system reorganization after stroke and the application of NIBS
      for neurorehabilitation. 

PMID- 25967761
TI  - [Erratum to: Role of evidence-based medicine in intensive care].

PMID- 25967760
TI  - Real-time core body temperature estimation from heart rate for first responders
      wearing different levels of personal protective equipment.
AB  - First responders often wear personal protective equipment (PPE) for protection
      from on-the-job hazards. While PPE ensembles offer individuals protection, they
      limit one's ability to thermoregulate, and can place the wearer in danger of heat
      exhaustion and higher cardiac stress. Automatically monitoring thermal-work
      strain is one means to manage these risks, but measuring core body temperature
      (Tc) has proved problematic. An algorithm that estimates Tc from sequential
      measures of heart rate (HR) was compared to the observed Tc from 27 US soldiers
      participating in three different chemical/biological training events (45-90 min
      duration) while wearing PPE. Hotter participants (higher Tc) averaged (HRs) of
      140 bpm and reached Tc around 39  degrees C. Overall the algorithm had a small
      bias (0.02  degrees C) and root mean square error (0.21  degrees C). Limits of
      agreement (LoA +/- 0.48  degrees C) were similar to comparisons of Tc measured by
      oesophageal and rectal probes. The algorithm shows promise for use in real-time
      monitoring of encapsulated first responders. PRACTITIONER SUMMARY: An algorithm
      to estimate core temperature (Tc) from non-invasive measures of HR was validated.
      Three independent studies (n = 27) compared the estimated Tc to the observed Tc
      in humans participating in chemical/ biological hazard training. The algorithm's
      bias and variance to observed data were similar to that found from comparisons of
      oesophageal and rectal measurements.

PMID- 25967762
TI  - Anaplastic Lymphoma Kinase Immunocytochemistry on Cell-Transferred Cytologic
      Smears of Lung Adenocarcinoma.
AB  - BACKGROUND: Anaplastic lymphoma kinase (ALK) immunohistochemical staining on
      formalin-fixed paraffin-embedded tissue or cell blocks (CB) has been reported as
      an effective alternative to fluorescence hybridization in situ (FISH) for the
      detection of ALK gene rearrangement. However, CB frequently lack adequate
      cellularity even when the direct smears are cellular. This study aims to assess
      the utility of ALK immunocytochemical (ICC) staining on direct smears using the
      cell transfer (CT) technique for the detection of ALK rearrangement. METHODS:
      Fine-needle aspiration (FNA) cases of lung adenocarcinoma in which the ALK status
      had been determined by FISH on CB or a concurrent biopsy were identified. ICC
      staining for ALK was performed on alcohol-fixed Papanicolaou-stained direct
      smears using the CT technique. ALK immunoreactivity was evaluated using a
      modified semiquantitative scale. Results were compared with those of FISH.
      RESULTS: A total of 47 FNA specimens were included. Five of 7 FISH-positive cases
      showed positive ALK ICC staining (71.4%), and 39 of 40 FISH-negative cases were
      negative on ALK ICC staining (97.5%). The overall correlation between ALK ICC and
      FISH was 93.6%. CONCLUSION: ICC performed on FNA smears using the CT technique is
      an alternative method for the assessment of ALK rearrangement, especially when CB
      lack adequate cellularity.

PMID- 25967764
TI  - Studies on laser-assisted Penning ionization by the optogalvanic effect in Ne/Eu
      hollow cathode discharge.
AB  - Laser-assisted Penning ionization (LAPI) is detected in a Ne/Eu hollow cathode
      (HC) discharge lamp using the pulsed optogalvanic (OG) method. In the Ne/Eu
      discharge, doubly ionized europium excited energy levels Eu[4f(7)(P(7/2,5/2)6)]
      lie within the thermal limit (~kT) from the laser-excited neon's energy level
      [2p(5)(P3/202)3p or 2p(8) (in Paschen notation)] lying at 149,848  cm(-1).
      Therefore, Penning ionization (PI) of europium atoms likely to occur into its
      highly excited ionic states is investigated. To probe the PI of europium, the
      temporal profiles of its counterpart neon OG signal are studied as a function of
      discharge current for the transitions (1s(4)->2p(8)) and (1s(2)->2p(2)),
      corresponding to 650.65 and 659.89 nm wavelengths, respectively. It is observed
      that PI of europium alters the overall discharge characteristics significantly
      and, hence, modifies the temporal profile of the OG signals accordingly. The
      quasi-resonant ionizing energy transfer collisions between laser-excited Ne 2p(8)
      atoms and electronically excited europium P(9/2)10 atoms are used to explain the
      LAPI mechanism. Such LAPI studies carried out in HC discharge could be useful for
      the discharge of a metal-vapor laser with appropriate Penning mixtures.

PMID- 25967763
TI  - Supporting Innovation in the UK: Care Act 2014. Developments in Social Care
      Legislation in England and the Medical Innovation Bill.

PMID- 25967765
TI  - Demonstration of multi-wavelength tunable fiber lasers based on a digital
      micromirror device processor.
AB  - Based on a digital micromirror device (DMD) processor as the multi-wavelength
      narrow-band tunable filter, we demonstrate a multi-port tunable fiber laser
      through experiments. The key property of this laser is that any lasing wavelength
      channel from any arbitrary output port can be switched independently over the
      whole C-band, which is only driven by single DMD chip flexibly. All outputs
      display an excellent tuning capacity and high consistency in the whole C-band
      with a 0.02 nm linewidth, 0.055 nm wavelength tuning step, and side-mode
      suppression ratio greater than 60 dB. Due to the automatic power control and
      polarization design, the power uniformity of output lasers is less than 0.008 dB
      and the wavelength fluctuation is below 0.02 nm within 2 h at room temperature. 

PMID- 25967766
TI  - Effect of the morphology on the anisotropic light scattering of polycarbonate
      (PC)/poly(styrene-co-acrylonitrile) (SAN)(70/30) blend.
AB  - The polycarbonate (PC)/poly(styrene-co-acrylonitrile) (SAN) (70/30) anisotropic
      light scattering sheet with controllable anisotropic degree was prepared by
      blending and hot stretching process. The morphological evolution of the dispersed
      particles for PC/SAN (70/30) blend during hot stretching was observed by a
      scanning electron microscope (SEM) and the effect of stretching deformation on
      the light scattering properties was investigated. The SEM photographs revealed
      that SAN particles deformed into ellipsoid during hot stretching. The scattering
      properties analysis results revealed the appearance of anisotropic light
      scattering for PC/SAN (70/30) blends with various deformations, and with the
      increase of stretching deformation, the anisotropic scattering degree increased,
      verifying the correctness of geometrical optical scattering theoretical analysis.

PMID- 25967767
TI  - Response of accommodation and vergence to electro-holographic images.
AB  - Studies on measuring accommodation and vergence responses of human vision are
      important to evaluate three-dimensional (3D) display technologies. Electro
      holography is expected to be an ideal 3D display. However, there has been little
      research on measuring responses to it. In this study, the static responses to
      electro-holographic images with a large visual field and correct stimuli were
      measured. In addition, responses to real objects were measured for comparison
      with those to displayed images. There were more subjects than in conventional
      studies for statistical analysis. The experimental results statistically
      confirmed the equivalence of the responses to electro-holographic images and
      those to real objects. Therefore, it was experimentally suggested that electro
      holography enables human vision to perform correct accommodation and vergence
      responses in accordance with the depths. 

PMID- 25967768
TI  - Absolute gauge block calibration using ultra-precise optical frequency
      synthesizer locked to a femtosecond comb.
AB  - In this paper, we report a gauge block (GB) calibration that is traceable to the
      SI unit of time, the second. Four ultra-stable optical telecommunication
      wavelengths near 1556 nm are obtained by locking a narrow-tuning-range fiber
      laser to a fiber-based femtosecond frequency comb. Since the GB calibration
      system does not operate at this region of spectrum, the superior frequency
      stability of the laser is transferred to the 778 nm region by using a waveguide
      periodically poled lithium niobate crystal. After applying the locking scheme,
      the stability and accuracy of the laser become better than 8*10(-12). The
      frequency-doubled light is sent through 30 m optical fiber to a GB
      interferometer, which is installed at a different laboratory in the same
      building. Using this calibration scheme, a GB with a nominal length of 100 mm is
      calibrated with an uncertainty of +/-52  nm. This uncertainty value is still
      comparable to or even better than other metrology laboratories for a similar
      block length.

PMID- 25967769
TI  - Lensless optical image processing based on two-dimensional Fresnel diffraction
      for synthetic-aperture imaging ladar.
AB  - A principle scheme of a lensless optical processor for synthetic-aperture imaging
      ladar (SAIL) is proposed. The collected data from SAIL is initially digitally
      added with a quadratic phase in the range direction. These data are then uploaded
      on a liquid crystal spatial light modulator to modulate the incident light. The
      target image is obtained through two-dimensional (2D) free-space Fresnel
      diffraction. The imaging process is mathematically analyzed using a 2D data
      collection equation of strip-mode side-looking SAIL. The design equation, imaging
      resolutions, and target-image compression ratios are presented. Based on this
      principle scheme, we construct an experimental optical SAIL processor and present
      the imaging result of data obtained from one SAIL demonstrator. The optical
      processor is found to exhibit the flexible property of digital processing, as
      well as the fast processing capability of optical means, because this optical
      processor is a lensless system. 

PMID- 25967770
TI  - Retrieval of phytoplankton and colored detrital matter absorption coefficients
      with remote sensing reflectance in an ultraviolet band.
AB  - The light absorption of phytoplankton and colored detrital matter (CDM), which
      includes contribution of gelbstoff and detrital matters, has distinctive yet
      overlapping features in the ultraviolet (UV) and visible domain. The CDM
      absorption (a(dg)) increases exponentially with decreasing wavelength while the
      absorption coefficient of phytoplankton (a(ph)) generally decreases toward the
      shorter bands for the range of 350-450 nm. It has long been envisioned that
      including ocean color measurements in the UV range may help the separation of
      these two components from the remotely sensed ocean color spectrum. An attempt is
      made in this study to provide an analytical assessment of this expectation. We
      started with the development of an absorption decomposition model [quasi
      analytical algorithm (QAA)-UV], analogous to the QAA, that partitions the total
      absorption coefficient using information at bands 380 and 440 nm. Compared to the
      retrieval results relying on the absorption information at 410 and 440 nm of the
      original QAA, our analyses indicate that QAA-UV can improve the retrieval of
      a(ph) and a(dg), although the improvement in accuracy is not significant for
      values at 440 nm. The performance of the UV-based algorithm is further evaluated
      with in situ measurements. The limited improvement observed with the field
      measurements highlights that the separation of a(dg) and a(ph) is highly
      dependent on the accuracy of the ocean color measurements and the estimated total
      absorption coefficient.

PMID- 25967771
TI  - Background elimination and interferometric capability in optical coherence
      tomography by a nonlinear optical gating based on type-II second-harmonic
      generation.
AB  - A novel method that uses nonlinear optical gating to control background
      illumination in optical coherence tomography is presented. With this method, the
      user can adjust the amount of undesired backscattering or eliminate it
      completely, which enables dark-field measurements. The interferometric capability
      of the method in a nonlinear optical regime is demonstrated with the coupling of
      three overlapping input waves to yield Fizeau fringes. The measurement of a 265
      nm step is performed to validate this method, which was originally conceived for
      3D MEMS characterization. 

PMID- 25967772
TI  - Analysis of tunable negative refraction in a lossy and extrinsic semiconductor.
AB  - In this work, within the framework of an inhomogeneous wave, we study the wave
      transmission at the boundary between air and a lossy extrinsic semiconductor of n
      type indium antimonide. Transmission properties such as negative refraction are
      specifically investigated. The choice of such a semiconductor enables us to study
      the tunable features in the negative refraction because its permittivity is a
      function of the frequency, the temperature, and the doping concentration. It is
      found that there exist a threshold temperature and a threshold frequency in order
      to obtain the negative refraction. The dependence of threshold temperature on the
      doping concentration and the operating frequency will be numerically
      demonstrated. The analysis of negative refraction can be used to study the
      electromagnetic response for a lossy and extrinsic semiconductor. 

PMID- 25967773
TI  - Extraction of optical constants from maxima of fringing reflectance spectra.
AB  - We propose a scheme to extract the refractive index and the extinction
      coefficient of dielectrics. The extraction needs only a reflectance spectrum with
      reliable successive maxima of fringing oscillations measured from a dielectric
      film that is either freestanding or on metal. With the film thickness known in
      advance, we determine the refractive index spectrum from the fringing oscillation
      periods and then the extinction coefficient spectrum from the upper envelope. The
      method is demonstrated to work well for GaAs and Ge. 

PMID- 25967774
TI  - Survey of emissivity measurement by radiometric methods.
AB  - A survey of the state of the art in the field of spectral directional emissivity
      measurements by using radiometric methods is presented. Individual quantity types
      such as spectral, band, or total emissivity are defined. Principles of emissivity
      measurement by various methods (direct and indirect, and calorimetric and
      radiometric) are discussed. The paper is focused on direct radiometric methods.
      An overview of experimental setups is provided, including the design of
      individual parts such as the applied reference sources of radiation, systems of
      sample clamping and heating, detection systems, methods for the determination of
      surface temperature, and procedures for emissivity evaluation. 

PMID- 25967775
TI  - Calibration of misalignment errors in composite waveplates using Mueller matrix
      ellipsometry.
AB  - Composite waveplates consisting of two or more single waveplates are widely used
      in optical instruments, such as ellipsometry, polarimetry, cryptography, and
      photoelasticity. Accurate calibration of the misalignment errors in composite
      waveplates is of great importance (to minimize or correct the spurious artifacts
      in the final collected spectral data of these instruments induced by the
      misalignment errors). In this paper, we choose the fast axis azimuth and the
      rotary angle of composite waveplates as the detected characteristic parameters to
      calibrate the misalignment errors in composite waveplates. We first derive a
      general analytical model to describe the relationship between the mislignment
      errors and the characteristic parameters, and then propose an inverse approach to
      the calibration of the misalignment errors in composite waveplates. An
      experimental device based on the dual rotating-compensator Mueller matrix
      ellipsometry principle is set up to measure the characteristic parameters of
      composite waveplates. Both numerical simulations and experiments on an MgF(2)
      MgF(2)-quartz triplate demonstrate the correctness and efficiency of the proposed
      approach. It is expected that the proposed approach can be readily extended to
      calibrate the misalignment errors in more complex composite waveplates.

PMID- 25967776
TI  - Waveform reconstruction for an ultrasonic fiber Bragg grating sensor demodulated
      by an erbium fiber laser.
AB  - Fiber Bragg grating (FBG) demodulated by an erbium fiber laser (EFL) has been
      used for ultrasonic detection recently. However, due to the inherent relaxation
      oscillation (RO) of the EFL, the detected ultrasonic signals have large
      deformations, especially in the low-frequency range. We proposed a novel data
      processing method to reconstruct an actual ultrasonic waveform. The noise
      spectrum was smoothed first; the actual ultrasonic spectrum was then obtained by
      deconvolution in order to mitigate the influence of the RO of the EFL. We proved
      by experiment that this waveform reconstruction method has high precision, and
      demonstrated that the FBG sensor demodulated by the EFL will have large practical
      applications in nondestructive testing. 

PMID- 25967777
TI  - Phase-sharing using a Mach-Zehnder interferometer.
AB  - A phase-sharing scheme using the Mach-Zehnder interferometric setup is
      demonstrated. Two coherent light fields of the same wavelength which have
      orthogonal polarizations are used as sources at the two ends of a Mach-Zehnder
      interferometer. They are made to interfere independently at the opposing ends of
      the interferometer so that the phase estimated by two observers at the two
      opposing ends of the interferometer is nearly identical. The scheme could in
      principle be used by two observers to simultaneously monitor and study a phase
      object inserted in one of the arms of the interferometer. A pseudorandom phase
      plate which mimics atmospheric turbulence is inserted in one of the arms of the
      interferometer to demonstrate that such a phase-sharing scheme could be converted
      to a secret-key sharing scheme. Shared secret-key generation is demonstrated
      through evaluation of the phase correlates of the shared phase samples available
      at their respective ends. The shared random phases could also be used in a more
      direct manner by the respective observers for random phase encryption of images. 

PMID- 25967778
TI  - Use of customizing kernel sparse representation for hyperspectral image
      classification.
AB  - Sparse representation-based classification (SRC) has attracted increasing
      attention in remote-sensed hyperspectral communities for its competitive
      performance with available classification algorithms. Kernel sparse
      representation-based classification (KSRC) is a nonlinear extension of SRC, which
      makes pixels from different classes linearly separable. However, KSRC only
      considers projecting data from original space into feature space with a
      predefined parameter, without integrating a priori domain knowledge, such as the
      contribution from different spectral features. In this study, customizing kernel
      sparse representation-based classification (CKSRC) is proposed by incorporating
      kth nearest neighbor density as a weighting scheme in traditional kernels.
      Analyses were conducted on two publicly available data sets. In comparison with
      other classification algorithms, the proposed CKSRC further increases the overall
      classification accuracy and presents robust classification results with different
      selections of training samples. 

PMID- 25967779
TI  - High peak power 4.7  ns electro-optic cavity dumped TEM(00) 1342-nm Nd:YVO(4)
      laser.
AB  - We presented the first demonstration of a high-peak power few-nanosecond pulse
      1342-nm Nd:YVO(4) laser by the combination of cavity dumping and in-band pumping.
      The maximum average output power of 3.2 W with Gaussian TEM(00) mode was obtained
      at the pulse repetition rate (PRR) of 10 kHz. The pulse width remained to be
      4.7+/-0.1  ns for the PRR from 2 to 10 kHz. The maximum pulse energy of 0.55 mJ
      was obtained at 2 kHz and the corresponding peak power was up to 117 kW. This is,
      to our knowledge, the shortest ns pulse width and the highest peak power for LD
      pumped 1.3 MUm TEM(00) lasers with an active Q-switch device.

PMID- 25967780
TI  - Full-field measurement of surface topographies and thin film stresses at elevated
      temperatures by digital gradient sensing method.
AB  - Thin film stresses in thin film/substrate systems at elevated temperatures affect
      the reliability and safety of such structures in microelectronic devices. The
      stresses result from the thermal mismatch strain between the film and substrate.
      The reflection mode digital gradient sensing (DGS) method, a real-time, full
      field optical technique, measures deformations of reflective surface
      topographies. In this paper, we developed this method to measure topographies and
      thin film stresses of thin film/substrate systems at elevated temperatures. We
      calibrated and compensated for the air convection at elevated temperatures, which
      is a serious problem for optical techniques. We covered the principles for
      surface topography measurements by the reflection mode DGS method at elevated
      temperatures and the governing equations to remove the air convection effects.
      The proposed method is applied to successfully measure the full-field topography
      and deformation of a NiTi thin film on a silicon substrate at elevated
      temperatures. The evolution of thin film stresses obtained by extending Stoney's
      formula implies the "nonuniform" effect the experimental results have shown. 

PMID- 25967781
TI  - Effect of soil temperature on optical frequency transfer through unidirectional
      dense-wavelength-division-multiplexing fiber-optic links.
AB  - Results of optical frequency transfer over a carrier-grade dense-wavelength
      division-multiplexing (DWDM) optical fiber network are presented. The relation
      between soil temperature changes on a buried optical fiber and frequency changes
      of an optical carrier through the fiber is modeled. Soil temperatures, measured
      at various depths by the Royal Netherlands Meteorology Institute (KNMI) are
      compared with observed frequency variations through this model. A comparison of a
      nine-day record of optical frequency measurements through the 2*298  km fiber
      link with soil temperature data shows qualitative agreement. A soil temperature
      model is used to predict the link stability over longer periods (days-months
      years). We show that optical frequency dissemination is sufficiently stable to
      distribute and compare, e.g., rubidium frequency standards over standard DWDM
      optical fiber networks using unidirectional fibers. 

PMID- 25967782
TI  - Phase quality map based on local multi-unwrapped results for two-dimensional
      phase unwrapping.
AB  - The efficiency of a phase unwrapping algorithm and the reliability of the
      corresponding unwrapped result are two key problems in reconstructing the digital
      elevation model of a scene from its interferometric synthetic aperture radar
      (InSAR) or interferometric synthetic aperture sonar (InSAS) data. In this paper,
      a new phase quality map is designed and implemented in a graphic processing unit
      (GPU) environment, which greatly accelerates the unwrapping process of the
      quality-guided algorithm and enhances the correctness of the unwrapped result. In
      a local wrapped phase window, the center point is selected as the reference
      point, and then two unwrapped results are computed by integrating in two
      different simple ways. After the two local unwrapped results are computed, the
      total difference of the two unwrapped results is regarded as the phase quality
      value of the center point. In order to accelerate the computing process of the
      new proposed quality map, we have implemented it in a GPU environment. The
      wrapped phase data are first uploaded to the memory of a device, and then the
      kernel function is called in the device to compute the phase quality in parallel
      by blocks of threads. Unwrapping tests performed on the simulated and real InSAS
      data confirm the accuracy and efficiency of the proposed method. 

PMID- 25967783
TI  - Stretched-pulse and solitonic operation of an all-fiber thulium/holmium-doped
      fiber laser.
AB  - Stretched-pulse operation of a mode-locked thulium/holmium-doped fiber laser has
      been demonstrated using a high numerical aperture (NA) fiber inside the laser
      cavity for intracavity dispersion compensation. The high NA fiber exhibits normal
      group-velocity dispersion allowing for the net-cavity dispersion to be positive.
      We experimentally investigate the laser dynamics as a function of the net-cavity
      dispersion, observing the transition from stretched-pulse to solitonic operation
      as the length of high NA fiber was reduced. In the stretched-pulse regime the
      laser produced pulses with a bandwidth of 30 nm and duration of 450 fs. Methods
      for compensating the third-order dispersion using high NA fibers are proposed. 

PMID- 25967784
TI  - Mode-field adapter for tapered-fiber-bundle signal and pump combiners.
AB  - We report on a novel mode-field adapter that is proposed to be incorporated
      inside tapered fused-fiber-bundle pump and signal combiners for high-power double
      clad fiber lasers. Such an adapter allows optimization of signal-mode-field
      matching on the input and output fibers. Correspondingly, losses of the combiner
      signal branch are significantly reduced. The mode-field adapter optimization
      procedure is demonstrated on a combiner based on commercially available fibers.
      Signal wavelengths of 1.55 and 2 MUm are considered. The losses can be further
      improved by using specially designed intermediate fiber and by dopant diffusion
      during splicing as confirmed by preliminary experimental results. 

PMID- 25967785
TI  - High-power spectral beam combining of linearly polarized Tm:fiber lasers.
AB  - To date, high-power scaling of Tm:fiber lasers has been accomplished by
      maximizing the power from a single fiber aperture. In this work, we investigate
      power scaling by spectral beam combination of three linearly polarized Tm:fiber
      MOPA lasers using dielectric mirrors with a steep transition from highly
      reflective to highly transmissive that enable a minimum wavelength separation of
      6 nm between individual laser channels within the wavelength range from 2030 to
      2050 nm. Maximum output power is 253 W with M(2)<2, ultimately limited by thermal
      lensing in the beam combining elements.

PMID- 25967786
TI  - New technique for the reduction of helicity-correlated instrumental asymmetries
      in photoemitted beams of spin-polarized electrons.
AB  - We present a new optical system that significantly reduces helicity-dependent
      instrumental intensity asymmetries. It is an extension of a previous scheme
      [Appl. Opt.47, 2465 (2008)], where one laser beam is split using a polarizing
      beam splitter into two with orthogonal linear polarizations. The beams are sent
      through a chopper, allowing only one to pass at a time. The two temporally
      separated beams are then spatially recombined using a second beam splitter. A
      liquid crystal retarder preceding the first beam splitter controls the relative
      intensity of the two oppositely polarized beams, allowing reduction of
      instrumental asymmetries. This system has been modified to include a spatial
      filter and a Pockels cell placed after the second beam splitter to act as a
      second active polarization element. Using this method, we can control
      instrumental asymmetries to ~5*10(-7) in 1 h of data taking, which is comparable
      to the precision achieved in "second-generation" high energy electron-nuclear
      scattering parity violation experiments.

PMID- 25967787
TI  - Interference effect from noise on range-gated laser ranging and tracking system.
AB  - Influence of high-repetition-rate noise on a range-gated laser ranging and
      tracking system (LRTS) is studied both theoretically and experimentally. The
      interference mechanism of high-repetition-rate noise on range gates is revealed.
      The interference effect, especially the effect caused by relative shift between
      signal and noise, is presented through theoretical analysis and numerical
      simulation. In order to verify the simulation model, both electrical closed
      circuit and optical circuit experiments are further conducted. Both the
      simulation model and experiment results show that both periodic and nonperiodic
      noise pulses can enter the range gates of a LRTS and affect its operation with
      both their high repetition rate and relative shift to echo pulses. 

PMID- 25967788
TI  - Investigation of optical and thermal properties of N-(alkyl-substituted)
      maleimides for use in zero-zero-birefringence polymer.
AB  - N-(alkyl-substituted) maleimides (RMIs) were proposed as materials useful for the
      development of a zero-zero-birefringence polymer that exhibits no birefringence.
      We analyzed the optical and thermal properties of poly(RMI)s, such as the
      refractive index, birefringence, and glass transition temperature. The
      characteristics of the obtained polymers varied significantly because the shift
      of the density and polarizability derived from the change of the substituent
      structure influenced the optical properties, and the bulkiness of the
      substituents influenced the thermal properties. We also designed a zero-zero
      birefringence polymer using N-ethyl maleimide (EMI) as a comonomer, and the
      obtained copolymer had no birefringence, relatively high heat resistance, and
      high transparency. 

PMID- 25967789
TI  - Accurate projector calibration method by using an optical coaxial camera.
AB  - Digital light processing (DLP) projectors have been widely utilized to project
      digital structured-light patterns in 3D imaging systems. In order to obtain
      accurate 3D shape data, it is important to calibrate DLP projectors to obtain the
      internal parameters. The existing projector calibration methods have complicated
      procedures or low accuracy of the obtained parameters. This paper presents a
      novel method to accurately calibrate a DLP projector by using an optical coaxial
      camera. The optical coaxial geometry is realized by a plate beam splitter, so the
      DLP projector can be treated as a true inverse camera. A plate having discrete
      markers on the surface is used to calibrate the projector. The corresponding
      projector pixel coordinate of each marker on the plate is determined by
      projecting vertical and horizontal sinusoidal fringe patterns on the plate
      surface and calculating the absolute phase. The internal parameters of the DLP
      projector are obtained by the corresponding point pair between the projector
      pixel coordinate and the world coordinate of discrete markers. Experimental
      results show that the proposed method can accurately calibrate the internal
      parameters of a DLP projector. 

PMID- 25967790
TI  - Generation of optical vortices by using binary vortex producing lenses.
AB  - Experimental high-quality optical vortices of different topological charges are
      generated by using a vortex producing lens with two phase levels. In our setup,
      the lens is displayed on a liquid-crystal spatial light modulator that only
      attains phase modulation of around 1.2pi. This achievement opens the real
      possibility of creating high-quality optical vortices with devices of very low
      phase modulation capacity. The experimental setup is fully described, and the
      considerations to set the optimal parameters to obtain high-quality optical
      vortices are discussed and experimentally established. The phase and intensity of
      the optical vortices are recovered. The phase is obtained through a phase
      shifting method that is directly programmed onto the modulator avoiding any class
      of mechanical displacement. 

PMID- 25967791
TI  - Comparison of different models for ground-level atmospheric turbulence strength
      (C(n)(2)) prediction with a new model according to local weather data for FSO
      applications.
AB  - Atmospheric parameters strongly affect the performance of free-space optical
      communication (FSOC) systems when the optical wave is propagating through the
      inhomogeneous turbulence transmission medium. Developing a model to get an
      accurate prediction of the atmospheric turbulence strength (C(n)(2)) according to
      meteorological parameters (weather data) becomes significant to understand the
      behavior of the FSOC channel during different seasons. The construction of a
      dedicated free-space optical link for the range of 0.5 km at an altitude of 15.25
      m built at Thanjavur (Tamil Nadu) is described in this paper. The power level and
      beam centroid information of the received signal are measured continuously with
      weather data at the same time using an optoelectronic assembly and the developed
      weather station, respectively, and are recorded in a data-logging computer.
      Existing models that exhibit relatively fewer prediction errors are briefed and
      are selected for comparative analysis. Measured weather data (as input factors)
      and C(n)(2) (as a response factor) of size [177,147*4] are used for linear
      regression analysis and to design mathematical models more suitable in the test
      field. Along with the model formulation methodologies, we have presented the
      contributions of the input factors' individual and combined effects on the
      response surface and the coefficient of determination (R(2)) estimated using
      analysis of variance tools. An R(2) value of 98.93% is obtained using the new
      model, model equation V, from a confirmatory test conducted with a testing data
      set of size [2000*4]. In addition, the prediction accuracies of the selected and
      the new models are investigated during different seasons in a one-year period
      using the statistics of day, week-averaged, month-averaged, and seasonal-averaged
      diurnal Cn2 profiles, and are verified in terms of the sum of absolute error
      (SAE). A Cn2 prediction maximum average SAE of 2.3*10(-13)  m(-2/3) is achieved
      using the new model in a longer range of dynamic meteorological parameters during
      the different local seasons.

PMID- 25967792
TI  - Effects of prestrain applied to poly(ethylene terephthalate) substrate on
      microstructures and morphologies of porous TiO(2) film and optical scattering
      behaviors of light.
AB  - A mold was designed to simulate a thin ceramic film coating on a soft, flexible
      substrate using a rotating deposition system. With this mold, three prestrains
      (2%, 4%, and 6%) were applied to a polyethylene terephthalate (PET) substrate
      before the deposition of a thin TiO(2) film. The contact angle of the substrate
      and, thus, the mean TiO(2) particle size were affected by the prestrain. The
      effects of the mean particle size of TiO(2) on the surface roughness and cavity
      area ratio of the porous film and on the scattering behavior of light were
      investigated. A goniophotometer and Advanced System Analysis Program were
      employed for the light analyses of bidirectional scatter distribution functions
      and their calibration. A spectrometer with an integrating sphere was applied to
      determine the total scatters (TSs) of transmittance and reflection. An increase
      in the prestrain increased the mean particle size of TiO(2) deposited on the
      substrate and, thus, the mean surface roughness, cavity/void depth, and cavity
      area ratio. PET/TiO(2) specimens with various prestrains were prepared that
      satisfy the Harvey-like model but without the isotropic, diffusive property in
      scatter. The bidirectional transmittance distribution function area and
      (TS)(transmittance) results are governed by the mean particle size and, thus, the
      cavity/void geometries and surface roughness. These values decrease with
      increasing PET prestrain. The bidirectional reflection distribution function area
      and (TS)(reflection), however, are governed by the adsorbed carbon and its
      absorption thickness. These values increase with increasing C(1s) peak value in x
      ray photoelectron spectroscopy spectra.

PMID- 25967793
TI  - Compact waveguide crossings with a cascaded multimode tapered structure.
AB  - A compact waveguide crossing constructed by a cascaded multimode tapered
      structure is numerically presented. By using an eigenmode expansion method, we
      observe that the phase difference between the two lowest guided modes can be
      changed after a multimode waveguide junction because of the coupling between
      these two guided modes. Accordingly, we propose a fourfold symmetric waveguide
      crossing composed of three cascaded tapered structures with Gaussian profiles on
      each branch. Analyzed by the finite difference time domain method, this waveguide
      crossing has the size of 4160  nm*4160  nm, insertion loss of 0.13 dB, cross talk
      of -43.5  dB, and backreflection of -33.6  dB at the wavelength of 1550 nm and
      broad transmission spectrum at the wavelength range of 1500-1600 nm. 

PMID- 25967794
TI  - Optical relative humidity sensor with high sensitivity based on a polyimide
      coated symmetrical metal-cladding waveguide.
AB  - An optical structure for relative humidity (RH) sensing based on a polyimide
      coated symmetrical metal-cladding waveguide is proposed. The diffusion of water
      molecules into the polyimide film leads to a combined change of thickness and
      refractive index. Due to the high sensitivity of ultrahigh-order modes, the
      interaction between water molecules and polyimide will give rise to a dramatic
      variation in the reflected light intensity. Our optical RH sensor exhibits a good
      linearity and a high RH resolution of approximately 0.16% for RH values ranging
      from 36% to 76%. In addition, it provides a short response time, a favorable
      stability over a long period, and a small degree of hysteresis. 

PMID- 25967795
TI  - Integration of an opto-chemical detector based on group III-nitride nanowire
      heterostructures.
AB  - The photoluminescence intensity of group III nitrides, nanowires, and
      heterostructures (NWHs) strongly depends on the environmental H(2) and O(2)
      concentration. We used this opto-chemical transducer principle for the
      realization of a gas detector. To make this technology prospectively available to
      commercial gas-monitoring applications, a large-scale laboratory setup was
      miniaturized. To this end the gas-sensitive NWHs were integrated with electro
      optical components for optical addressing and read out within a compact and
      robust sensor system. This paper covers the entire realization process of the
      device from its conceptual draft and optical design to its fabrication and
      assembly. The applied approaches are verified with intermediate results of
      profilometric characterizations and optical performance measurements of
      subsystems. Finally the gas-sensing capabilities of the integrated detector are
      experimentally proven and optimized.

PMID- 25967797
TI  - Improved regularization reconstruction from sparse angle data in optical
      diffraction tomography.
AB  - In this paper, we propose an improved deterministic regularization algorithm to
      handle the sparse angle data problem in optical diffraction tomography. Based on
      optical diffraction tomography and the deterministic regularization algorithm,
      the regularization iteration is performed in the space domain and the frequency
      domain simultaneously, which greatly reduces the computational cost. By applying
      piecewise-smoothness and positivity constraints as the penalty function, the
      missing frequency spectrum is effectively recovered and the internal refractive
      index distribution of the specimen is accurately reconstructed. Using simulated
      and experimental results, we show that the proposed regularization algorithm
      allows accurate refractive index reconstruction from very sparse angle data in
      optical diffraction tomography. 

PMID- 25967796
TI  - Dual-camera design for coded aperture snapshot spectral imaging.
AB  - Coded aperture snapshot spectral imaging (CASSI) provides an efficient mechanism
      for recovering 3D spectral data from a single 2D measurement. However, since the
      reconstruction problem is severely underdetermined, the quality of recovered
      spectral data is usually limited. In this paper we propose a novel dual-camera
      design to improve the performance of CASSI while maintaining its snapshot
      advantage. Specifically, a beam splitter is placed in front of the objective lens
      of CASSI, which allows the same scene to be simultaneously captured by a
      grayscale camera. This uncoded grayscale measurement, in conjunction with the
      coded CASSI measurement, greatly eases the reconstruction problem and yields high
      quality 3D spectral data. Both simulation and experimental results demonstrate
      the effectiveness of the proposed method. 

PMID- 25967798
TI  - Temperature increase effects on a double-pass cavity type II second-harmonic
      generation: a model for depleted Gaussian continuous waves.
AB  - In this work, the effect of temperature increase on the efficiency of a double
      pass cavity type II second-harmonic generation (SHG) is investigated. To this
      end, a depleted wave model describing the continuous-wave SHG process with
      fundamental Gaussian waves was developed. First, six coupled equations were
      proposed to model a double-pass cavity to generate the second harmonic of a
      Gaussian fundamental wave in type II configuration. Then, the effect of
      temperature increase in the nonlinear crystal due to the optical absorption was
      modeled. To do this, a mismatched phase arising from changes in refractive
      indices was added to the coupled equations. Although the nondepleted assumption
      is usually used in such problems, a simultaneous solving of coupled equations
      with assumption of fundamental beam depletion was performed. The results were
      obtained by a homemade code written in Intel Fortran, and show how the efficiency
      of the SHG process decreases when the crystal is warmed up by 5, 10, and 15 K.
      Dramatic reductions in SHG efficiency were observed due to small changes in
      temperature. The results show excellent agreement with the experimental data
      [Opt. Commun.173, 311-314 (2000)].

PMID- 25967799
TI  - Elemental image array generation based on discrete viewpoint pickup and window
      interception in integral imaging.
AB  - We present a method to generate the elemental image array (EIA) in integral
      imaging in this paper. The discrete viewpoint image array is captured from a
      discrete viewpoint pickup platform and is treated by a window interception
      algorithm to obtain the subimage array (SIA). The EIA can be obtained from the
      SIA according to the transformation relationship between the EIA and SIA. We
      employ the EIA to display in the integral imaging system, indicating that the
      proposed method can truly represent the structure of the objects. 

PMID- 25967800
TI  - Detection method of inclination angle in image measurement based on improved
      triangulation.
AB  - Image distortion seriously affects the accuracy in microscope image measurement.
      One source of such distortion is related to the tilting of the microscope stage
      during laser scanning, thereby resulting in various degrees of inclination
      angles. This paper describes a novel technique that improves the traditional
      laser triangulation method by using multiple parallel laser beams that can solve
      the inclination problem. Moreover, a multi-light-spot measurement device, based
      on the improved laser triangulation technique, is proposed that can accurately
      detect the degree and directions of the inclination angles in real time.
      Furthermore, experimental results generated from a prototype of this device show
      that the new measurement system can effectively detect small inclination angles
      at a precision up to +/-0.5  MUrad. 

PMID- 25967801
TI  - Controlling the optical fiber output beam profile by focused ion beam machining
      of a phase hologram on fiber tip.
AB  - A phase hologram was machined on an optical fiber tip using a focused ion beam
      (FIB) system so that a ring-shaped beam emerges from the fiber tip. The fiber
      used for this work was a commercial single-mode optical fiber patch cable for a
      design wavelength of 633 nm with a germanosilicate core. The ring-shaped beam was
      chosen to ensure a simple geometry in the required phase hologram, though the
      Gerchberg-Saxton algorithm can be used to calculate a hologram for an arbitrary
      beam shape. The FIB machining took approximately 45 min at 30 kV and 200 pA. The
      radius of the resulting ring beam was 0.083 m at 1 m standoff, as compared to 0.1
      m as was initially desired. Results suggest that this imaging technique may
      provide a basis for a beam-shaping method with several advantages over the
      current commercial solutions, having permanent alignment, compactness, and
      mechanical robustness. However, it would appear that minimizing the speckle
      pattern will remain a critical challenge for this technique to become widely
      implemented. 

PMID- 25967802
TI  - Implementation of a widely tunable microwave signal generator based on dual
      polarization fiber grating laser.
AB  - In this paper, we demonstrate the implementation of a widely tunable microwave
      signal generator based on a dual-polarization fiber grating laser. The laser
      contains two strong, wavelength-matched Bragg gratings photoinscribed in an Er
      doped fiber and emits two polarization modes when pumped with a 980 nm laser
      diode. By beating the two modes, a microwave signal with a signal-to-noise ratio
      over 60 dB can be obtained. For a free running laser the fluctuations in
      intensity and frequency of the microwave signal are +/-1  dB and +/-5  kHz,
      respectively, and the noise level is about -40  dBc/Hz at 1 kHz. The frequency
      can be continuously tuned from 1.8 to 15.1 GHz, by transversely loading the laser
      cavity and changing the intracavity birefringence by use of a piezoelectric
      transducer-based mechanical device. The measured response time rate of tuning is
      about 90 MHz/MUs and the intensity fluctuation at different frequencies is less
      than +/-1.5  dB. The frequency fluctuation under loading is controlled within 1
      MHz by introducing an electrical feedback. 

PMID- 25967803
TI  - Study on particle size dependence of axial trapping efficiency.
AB  - An optical tweezers system using laser beams with a Gaussian intensity profile
      and doughnut intensity profiles made by hollow core optical fiber and axicon
      lenses, respectively, was constructed. The axial trapping efficiencies for the
      three intensity profiles were measured and compared with each other. The particle
      size dependence of axial trapping efficiencies in the range of the particle
      diameter from 1 to 20 MUm were analyzed by using the modified ray optics model
      [Appl. Opt.33, 1735 (1994)].

PMID- 25967804
TI  - Tunable random distributed feedback fiber laser operating at 1 MUm.
AB  - A tunable random distributed feedback (RDFB) fiber laser operating at 1 MUm is
      presented, which consists of a piece of ytterbium-doped fiber, a manual tunable
      filter and a 1-km-long single-mode fiber that provides RDFB. The wavelength of
      the RDFB fiber laser can be tuned continuously from 1040 to 1090 nm with a
      linewidth of about 0.4 nm. Power output maintains good flatness in the 50 nm
      tuning range, with fluctuations within 1 dB. It is the first reported tunable
      RDFB fiber laser working at 1 MUm as far as we know. 

PMID- 25967805
TI  - Two-dimensional high-speed and long-range tomography and profilometry using
      liquid-crystal Fabry-Perot resonator.
AB  - A two-dimensional high-speed, long-range tomography and profilometry based on a
      low-coherence optical interferometry has been developed. A liquid-crystal Fabry
      Perot resonator is fabricated to be a low-coherence optical frequency comb
      generator for expanding the measurement depth of the tomography and profilometry.
      The line-shape interference fringes with the individual fringe orders are
      obtained by a CCD camera in real time. The relative optical length, corresponding
      to the sample depth information, can be derived from the positions of the
      interference fringes on the CCD camera and their corresponding fringe orders. The
      fringe orders can be rapidly calculated using the effectiveness of the changeable
      extraordinary refractive index of the liquid-crystal material of the resonator.
      The finesse of the liquid-crystal resonator is approximate 9, giving an expansion
      of the measurement range of up to 9-fold (~8  mm depth) with a resolution of
      profilometry and tomography of 3.7 MUm and 11 MUm, respectively. 

PMID- 25967806
TI  - Further enhancement of light extraction efficiency from light emitting diode
      using triangular surface grating and thin interface layer.
AB  - Analysis has been done of improvement of forward directional light extraction
      efficiency of light emitting diodes (LEDs) by surface patterning of different
      types of one-dimensional profiles on indium-zinc-oxide films developed recently
      by our group using sol-gel technique. Finite-difference time-domain simulations
      by MEEP software have been used for this purpose. From the analysis, it is found
      that the patterned film is suitable for near-infrared LED. The optimized
      structure, which gives maximum improvement at around 1.040 MUm wavelength, is
      determined and fabricated using soft lithography. Further enhancement of the
      light output of the LED with the fabricated gratings is possible by introducing
      an interlayer within the top contact layer. The mathematical formulation of the
      coupling of light in structured/multilayered surfaces is also discussed. 

PMID- 25967807
TI  - Calibration function for an experimental setup for the measurement of irradiance
      distributions via a transmitting diffuser.
AB  - We describe a procedure to estimate the calibration function for an experimental
      setup that contains a transmitting diffuser whose bidirectional transmittance
      distribution function for light transmitted in normal direction is nearly
      independent of the incidence angle. This type of diffusing screen may be used in
      experimental setups to measure the irradiance distribution in the focal plane of
      concentrator optics that have large angles of incidence in the focal plane. It is
      shown that the influence of this screen and of the remaining components on the
      irradiance distribution may be described empirically by a Gaussian function and
      thus may be corrected for. Furthermore, it is demonstrated that the correction is
      necessary to avoid an underestimation of the concentrator optics' ability to
      concentrate the incoming radiation. 

PMID- 25967808
TI  - Gray change detection method for damage monitoring in materials.
AB  - A gray change detection method has been proposed to monitor damage in materials.
      The normalized parameter C has been defined by the displacement and the gray
      level value, which can reflect the gray change of each pixel point in the region
      of interest of the image. A zero deformation experiment has been done to discuss
      the feature of gray change caused by many factors except the damage. The results
      show that local expanded regions with concentrations of C can be considered as
      the damage regions. The uniaxial tensile experiments for an artificial rock
      specimen and a polycarbonate specimen have been done to verify the performance of
      the proposed method. The results show that the proposed method is effective for
      monitoring surface cracks in rocks and the shear band in polymers. This work
      provides a useful method for damage monitoring in materials. 

PMID- 25967809
TI  - Effects of color centers absorption on the spectrum of the temperature-dependent
      radiation-induced attenuation in fiber.
AB  - Spectra ranging from 800 to 1650 nm of the temperature-dependent radiation
      induced attenuation (RIA) in the irradiated and sufficiently annealed fiber with
      germanium and phosphorous dopant has been measured. These RIA spectra were
      investigated based on the mechanism of color centers absorption. With the
      configurational coordinate model, these RIA spectra were decomposed by the
      absorption bands of three kinds of color centers. The effects of color centers
      absorption on the spectrum of temperature-dependent RIA is discussed by comparing
      the absorption intensity of different color centers at a same wavelength.
      Moreover, the temperature-dependent RIA of the fiber has been measured separately
      at 850, 1310, and 1550 nm. The measured results agreed well with the analysis of
      RIA spectra. 

PMID- 25967810
TI  - Modified rod-in-tube for high-NA tellurite glass fiber fabrication: materials and
      technologies.
AB  - In this paper, we report the whole fabrication process for high-numerical
      aperture (NA) tellurite glass fibers from material preparation to preform
      fabrication, and eventually, fiber drawing. A tellurite-based high-NA (0.9)
      magneto-optical glass fiber was drawn successfully and characterized. First,
      matchable core and cladding glasses were fabricated and matched in terms of
      physical properties. Second, a uniform bubble-free preform was fabricated by
      means of a modified rod-in-tube technique. Finally, the fiber drawing process was
      studied and optimized. The high-NA fibers (?(core), 40-50 MUm and ?(cladding),
      120-130 MUm) so obtained were characterized for their geometrical and optical
      properties.

PMID- 25967811
TI  - Z-scan measurement of the nonlinear refractive index of Nd(3+), Y(3+)-codoped
      CaF(2) and SrF(2) crystals.
AB  - By performing the Z-scan measurements at 800 nm using a femtosecond pulsed laser,
      we are able to characterize the nonlinear refractive indices of Nd, Y codoped
      CaF(2) and SrF(2) crystals. Based on our measured results, we conclude that the
      doped fluoride crystal possesses a small nonlinear refractive index and the
      doping of Nd(3+) and Y(3+) ions in CaF(2) can change its third-order nonlinear
      index, but the contribution is minor. The doped fluoride crystal may have large
      potential to be developed as the next generation of gain material for a high
      energy laser system.

PMID- 25967812
TI  - Optical properties and residual stress in Nb-Si composite films prepared by
      magnetron cosputtering.
AB  - This paper investigates Nb-Si metal composite films with various proportions of
      niobium in comparison to pure Nb films. Films were prepared by two-target RF-DC
      magnetron cosputtering deposition. The optical properties and residual stress
      were analyzed. A composition of Nb(0.74)Si(0.26) was chosen toward the design and
      fabrication of solar absorbing coatings having a high absorption in a broad
      wavelength range, a low residual stress, and suitable optical constants. The
      layer thicknesses and absorption characteristics of the Nb-Si composite films
      adhere more closely to the design than other coatings made of dielectric film
      materials.

PMID- 25967813
TI  - Automatic inspection of density in yarn-dyed fabrics by utilizing fabric light
      transmittance and Fourier analysis.
AB  - Yarn density measurement is a significant part of yarn-dyed fabric analysis,
      traditionally based on reflective image analysis. In this paper, utilizing fabric
      light transmittance, a method for two-dimensional discrete Fourier transform (2D
      DFT) analysis on the transmission fabric image is developed for fabric density
      inspection. First, the power spectrum is generated from the fabric image by a 2D
      DFT. Next, the yarn skew angles are detected based on the power spectrum
      analysis. Then the fabric image is reconstructed by an inverse 2D DFT. Finally,
      projection curves are generated from the reconstructed images and the number of
      yarns is counted according to the peaks and valleys to obtain the fabric density.
      Through a comparison between analysis on the reflective and transmission images
      of multiple-color fabrics, it is proved that the latter method can segment the
      yarns with more satisfactory accuracy. Furthermore, the experimental and
      theoretical analyses demonstrate that the proposed method is effective for the
      density inspection of yarn-dyed fabrics with good robustness and great accuracy. 

PMID- 25967814
TI  - High-numerical-aperture high-reflectivity focusing reflectors using concentric
      circular high-contrast gratings.
AB  - We present a concise approach to design focusing reflectors using concentric
      circular subwavelength high-contrast gratings (CCSW-HCGs). With this method, we
      design a high-numerical-aperture, high-reflectivity CCSW-HCG focusing reflector.
      By designing the CCSW-HCG structure, the grating can give the target phase front
      of reflected light while maintaining a high reflectivity. The properties of
      focusing and reflection are numerically studied with the finite element method.
      Simulation results show that, when the incident wavelength is 1550 nm, the
      reflectivity is 0.8538, and the numerical aperture is up to 0.9213. At the
      reflection focal plane, the full width at half-maximum of the field distribution
      is 0.9845 MUm. Furthermore, the CCSW-HCG can simultaneously focus the reflected
      and transmitted light and has a strong robustness. 

PMID- 25967815
TI  - Naked eye visibility of Sirius in broad daylight.
AB  - Sirius was spotted with the naked eye at broad daylight by looking along the
      finder of a 1 m telescope on La Palma Observatory at a 2370 m height. Sun
      elevation was 73 degrees ; Sirius was nearly straight under the Sun at 37 degrees
      elevation. The sky radiance, although not recorded directly, could be determined
      from the simultaneously obtained high-precision wavelength-dependent sky
      polarization data near Sirius. This was done by fitting the polarization data
      with the doubling-adding KNMI (DAK) radiative transfer model, which provided the
      values of the surface albedo and of the aerosol optical thickness required for
      determining the absolute sky radiance. Our analysis implies that Sirius, when
      positioned overhead, can be a daytime naked eye object from sea level even if its
      culmination occurs at solar noon. It also suggests that the second-brightest star
      (Canopus), if positioned overhead, could be perceptible even at solar noon. 

PMID- 25967816
TI  - Seeing, adapting to, and reproducing the appearance of nature.
AB  - The perception of color in nature is a complex multidimensional phenomenon. The
      vast range and high dimensionality of the light stimulus in a natural scene is
      reduced in range and dimension by the human visual system. The color experience
      is reduced to the appearance attributes of brightness, lightness, colorfulness,
      chroma, saturation, and hue from spectral energy distributions in the scene,
      while the vast range of light levels present in the world is reduced to a more
      manageable perceptual range through local adaptation. These processes set the
      stage for our efforts to capture, process, and reproduce the colors of nature as
      well as make artistic interpretations of them. This paper reviews the challenges
      involved in accurately capturing and reproducing optical phenomena observed in
      nature. 

PMID- 25967817
TI  - Observation, analysis, and reconstruction of a twinned rainbow.
AB  - A photograph of a twinned rainbow, obtained on 11 May, 2012, in Dresden, Germany,
      is precisely calibrated with respect to lens projection and camera orientation.
      Since the twinning was only located in a part of the picture, it was possible to
      read out the red-green-blue intensity data from both a twinned and nontwinned
      position of the rainbow. These data were fitted with modeled spectra for
      polydisperse drop distributions, which were calculated with a Debye series
      algorithm and shifted in the scattering angle to account for the nonspherical
      shape of natural raindrops. The shift data were acquired from raytracing through
      realistic raindrop shapes modeled by two conjoined half-spheroids of different
      oblateness. Effective drop size distributions along the line of sight are derived
      from the fit for the two sampling positions and used to generate a true-color
      simulation of the original photograph. By this, the optical determination of
      physical rainfall properties is demonstrated. 

PMID- 25967818
TI  - Photographic observation and optical simulation of a pollen corona display in
      Japan.
AB  - Brightness and chromaticity profiles were extracted from a vivid solar corona
      image taken with a digital camera in Sendai, Japan, to compare with a radiative
      transfer simulation applying Lorenz-Mie theory and single-scattering
      approximation. The comparison revealed suspended particles having a narrow
      particle size distribution peaking at radius 14.5 MUm. Presumably, pollen of an
      indigenous coniferous tree, the cryptomeria (Cryptomeria japonica), is
      responsible for the corona display. The extracted brightness and chromaticity
      profiles are reproduced well by assuming the presence of a water soluble aerosol
      and dust in addition to the pollen. We find that photographic analysis of corona
      displays, similar to that used to measure cloud particle size, is applicable to
      estimating pollen particle size distribution and column number density. 

PMID- 25967819
TI  - Colors of thermal pools at Yellowstone National Park.
AB  - The brilliant visible colors of various hot springs and pools in Yellowstone
      National Park are explained with a combination of scattering from the water and
      from microbial mats that coat the bottoms of these thermal features. A simple 1D
      radiative transfer model was used to simulate the colors recorded in visible
      photographs and the spectrum of light making up these colors. The model includes
      attenuation in water by absorption and molecular scattering as well as reflection
      characteristics of the microbial mats and surface reflection of the water. Pool
      geometries are simulated as simple rough cones scaled to have depths and widths
      that match published data. Thermal images are also used to record the spatial
      distribution of water skin temperature. The measurements and simulations confirm
      that colors observed from shallow-water features arise primarily from the
      spectral properties of the microbial mat, which is related to the water
      temperature, while colors observed from deeper water arise primarily from the
      wavelength-dependent absorption and scattering in the water. 

PMID- 25967820
TI  - Mother-of-pearl cloud particle size and composition from aircraft-based
      photography of coloration and lidar measurements.
AB  - During a Stratospheric Aerosol and Gas (SAGE)-III Ozone Loss and Validation
      Experiment (SOLVE)-II science flight on 4 February 2003, a mother-of-pearl cloud
      over Iceland was underflown by the NASA DC-8 and measured with the lidars
      onboard. In addition, color photos were taken during the approach. Aided by
      extensive modeling of cloud coloration, the main results of the analysis of this
      unique data set are: (1) the polar stratospheric cloud was mountain wave-induced
      and of type II; (2) the spectacular color display was caused by ice particles
      with sizes around 2 MUm. 

PMID- 25967821
TI  - Shadows.
AB  - We investigate the brightness distribution in and around outdoor shadows (for a
      variety of sky conditions) using modeling and field measurements. The dominant
      factor influencing the brightness of a shadow is the solid angle subtended by the
      object blocking the Sun. Occulters at the zenith that subtend a small solid angle
      cast shadows that are bright and possess a nearly uniform brightness across their
      extent. Shadows from large occulters are much darker and their brightness varies
      considerably, being darkest at their centers. For nonzenith occulters, the
      proximal (nearest the Sun) side of the shadow is darker than the distal side and
      the shadow will be darkest beneath the center of the occulter. Occulters (e.g.,
      tree or cloud) influence the brightness of sunlit portions near the shadow
      because they block part of the sky and reflect light into the shadow. The aureole
      has a significant influence on the brightness of shadow edges. Semi-analytic
      formulations for the brightness in shadows are presented, and analytic
      expressions in wells and tunnels are derived. 

PMID- 25967822
TI  - Red-based cumulus.
AB  - Observations and model simulations of cumulus clouds whose bases are tinted red
      when the Sun is well above the horizon are presented. Conditions for seeing red
      bases include (1) a red underlying surface (which may consist of dust clouds, as
      from haboobs) with high albedo, (2) small fractional cloud cover when the Sun is
      far enough below the zenith for direct sunlight to illuminate much of the surface
      directly below and around cloud base, (3) optically thick clouds so that the
      bases are dark, and (4) clouds with bases that are near enough to the observer to
      appear high in the sky so that the admixture of scattered light from the
      intervening atmosphere is minimized. 

PMID- 25967823
TI  - Inferior mirages: an improved model.
AB  - A quantitative model of the inferior mirage is presented, based on a realistic
      temperature profile in the convective boundary layer, using Monin-Obukhov
      similarity theory. The top of the inverted image is determined by the logarithmic
      part of the profile; the bottom is the apparent horizon, which depends on optical
      obstruction by roughness elements. These effects of surface roughness are
      included in the model, which is illustrated with a simulation. The vertical
      magnification varies throughout the mirage, becoming infinite at Minnaert's ill
      named "vanishing line"-which makes green flashes apparent to the naked eye. 

PMID- 25967824
TI  - A note on the radiance distributions of halos due to scattering by randomly
      orientated crystals.
AB  - The radiance distribution of light scattered by randomly oriented ice crystals
      differs fundamentally from the radiance distribution of light scattered by
      spherical raindrops or by preferentially oriented ice crystals. A formalism for
      light scattering by randomly oriented crystals is given and applied to four
      examples, among them the circular 22 degrees  halo and the antisolar halospot,
      the latter being the glory analogue for ice crystals. A long-standing
      misconception about the nature of the radiance distribution of circular halos is
      quantified and discussed. 

PMID- 25967825
TI  - The prodigious halo of the other Huygens.
AB  - At the height of the ceremony in the Principality of Orange of the restoration of
      the sovereignty of the House of Nassau in 1665, a ceremony led by Christiaan's
      father, Constantijn Huygens, a "solar crown" appeared in the sky, apparently a
      divine sign of approval. A nearly forgotten contemporary color engraving of this
      miraculous event has survived. Constantijn seized the opportunity by using to his
      advantage the general euphoria among the citizens caused by the appearance. We
      argue that Constantijn knew exactly what was going on in the sky because of his
      son's work on halo theory. Given its brightness and its time of appearance, it
      seems plausible that the most prominent halo in the Orange halo display was a
      circumscribed halo rather than the more familiar but bleaker circular 22 degrees 
      halo. The same probably holds for most of the other high-sun halos that caused
      general consternation, dating from the Octavian halo of 44 BC, to the Chernobyl
      halo of 1986, and indeed up to bright high-sun halos of the present. 

PMID- 25967826
TI  - Measuring and modeling twilight's Belt of Venus.
AB  - The Belt of Venus (or antitwilight arch) is a reddish band often seen above the
      antisolar horizon during clear civil twilights, and immediately beneath it is the
      bluish-gray earth's shadow (or dark segment) cast on the atmosphere. Although
      both skylight phenomena have prompted decades of scientific research,
      surprisingly few measurements exist of their spectral, colorimetric, and
      photometric structure. Hyperspectral imaging of several clear twilights supplies
      these missing radiometric details and reveals some common spectral features of
      the antisolar sky at twilight: (1) color differences between the dark segment and
      the sunlit sky above the antitwilight arch are small or nil; (2) antisolar color
      and luminance extremes usually occur at different elevation angles; and (3) the
      two twilight phenomena are most vivid for modest aerosol optical depths. A second
      order scattering model that includes extinction by aerosols and ozone provides
      some preliminary radiative transfer explanations of these twilight features'
      color and brightness. 

PMID- 25967827
TI  - Some elementary but surprising facts about the Sun's path at sunset.
AB  - For temperate latitudes, the assumed path of the Sun across the sky would suggest
      that the angle between the horizon and the Sun's path at sunset would be much
      greater on the first day of summer when the Sun is high in the sky at noon than
      on the first day of winter when the Sun's noon elevation is 47 degrees  lower.
      The angle that the Sun's path makes with the horizon at sunset is, however,
      exactly the same on the first day of summer and the first day of winter-for any
      latitude. For 43 degrees  north latitude, although the range of angles over a
      year for the Sun's noon elevation is 47 degrees , the range of angles between the
      horizon and the Sun's path at sunset is only 5 degrees . 

PMID- 25967828
TI  - Caustics due to complex water menisci.
AB  - Shadows of leaves and other objects that can float on the surface of still or
      slowly flowing water such as a pond or a gently flowing stream have shapes that
      frequently look nothing like their boundaries because of meniscus effects.
      Menisci can either refract light into the shadow region making it brighter, or
      away from it extending the area of darkness. Generally speaking one will find
      both effects in the shadows of leaves with complicated outlines. In this paper we
      present an approximate theoretical model for the light intensity in these shadow
      regions with results of laboratory experiments and computer simulations matching
      our calculations. The calculations indicate a minimum depth for the water of ~10 
      cm for typical floating leaves at which caustic structures form in the shadows.
      For depths significantly less than this, the shadows will more or less match the
      outline of the leaf. But for depths much greater the shadows will be
      significantly different, often not looking anything like the leaf itself. 

PMID- 25967829
TI  - Influence of scattering surface inclination on the opposition effect.
AB  - New observations and analyses are presented of the opposition effect on mud
      cracks (mud polygons) on desert playas. The enhanced brightness of the surface
      near the antisolar point has been previously and correctly ascribed to two
      sources: shadow-hiding and coherent backscatter. The observations reported here
      suggest that a third optical mechanism influences the OE: some parts of the mud
      polygon are more strongly illuminated than others, depending on the angle of
      incidence of sunlight. This causes the areas facing the observer and the sun to
      be brighter than the rest of the polygon field. This mechanism, called
      "dilution," also should occur in all OEs. 

PMID- 25967830
TI  - Recovering of weather degraded images based on RGB response ratio constancy.
AB  - Images captured under bad weather conditions suffer from poor contrast and
      visibility. These effects are noticeable for haze, mist, fog, or dust storms. We
      have proposed a recovering method for images captured for several adverse weather
      conditions based on the RGB response ratio constancy under illuminant changes.
      This algorithm improves the visibility, contrast, and color in degraded images
      with low computational times. We obtain results similar to those from previously
      published deweathering methods but with no prior information about the image
      content or atmospheric parameters needed. 

PMID- 25967831
TI  - Tropospheric haze and colors of the clear daytime sky.
AB  - To casual observers, haze's visible effects on clear daytime skies may seem
      mundane: significant scattering by tropospheric aerosols visibly (1) reduces the
      luminance contrast of distant objects and (2) desaturates sky blueness. However,
      few published measurements of hazy-sky spectra and chromaticities exist to
      compare with these naked-eye observations. Hyperspectral imaging along sky
      meridians of clear and hazy skies at one inland and two coastal sites shows that
      they have characteristic colorimetric signatures of scattering and absorption by
      haze aerosols. In addition, a simple spectral transfer function and a second
      order scattering model of skylight reveal the net spectral and colorimetric
      effects of haze. 

PMID- 25967832
TI  - Adaptive exposure estimation for high dynamic range imaging applied to natural
      scenes and daylight skies.
AB  - Digital imaging of natural scenes and optical phenomena present on them (such as
      shadows, twilights, and crepuscular rays) can be a very challenging task because
      of the range spanned by the radiances impinging on the capture system. We propose
      a novel method for estimating the set of exposure times (bracketing set) needed
      to capture the full dynamic range of a scene with high dynamic range (HDR)
      content. The proposed method is adaptive to scene content and to any camera
      response and configuration, and it works on-line since the exposure times are
      estimated as the capturing process is ongoing. Besides, it requires no a priori
      information about scene content or radiance values. The resulting bracketing sets
      are minimal in the default method settings, but the user can set a tolerance for
      the maximum percentage of pixel population that is underexposed or saturated,
      which allows for a higher number of shots if a better signal-to-noise ratio (SNR)
      in the HDR scene is desired. This method is based on the use of the camera
      response function that is needed for building the HDR radiance map by stitching
      together several differently exposed low dynamic range images of the scene. The
      use of HDR imaging techniques converts our digital camera into a tool for
      measuring the relative radiance outgoing from each point of the scene, and for
      each color channel. This is important for accurate characterization of optical
      phenomena present in the atmosphere while not suffering any loss of information
      due to its HDR. We have compared our method with the most similar one developed
      so far [IEEE Trans. Image Process.17, 1864 (2008)]. Results of the experiments
      carried out for 30 natural scenes show that our proposed method equals or
      outperforms the previously developed best approach, with less shots and shorter
      exposure times, thereby asserting the advantage of being adaptive to scene
      content for exposure time estimation. As we can also tune the balance between
      capturing time and the SNR in our method, we have compared its SNR performance
      against that of Barakat's method as well as against a ground-truth HDR image of
      maximum SNR. Results confirm the success of the proposed method in exploiting its
      tunability to achieve the desired balance of total Deltat and SNR. 

PMID- 25967833
TI  - Optical transmission properties of Pentelic and Paros marble.
AB  - Ancient Greek and Roman sources report that the statue of Zeus in Olympia had a
      head, and in particular eyes, similar to the description of Zeus by Homer, so we
      think that the statue was visible to the human eye. Since the temple was 12 m
      high, and had a small door and no windows, the illumination of the statue by
      conventional media is questionable. The aim of this paper is to characterize the
      optical transmission of Paros and Pentelic marble to demonstrate that it was
      possible to have the Zeus temple illuminated through the roof marble tiles.
      Spectral absolute transmittance measurements were taken in samples with different
      thicknesses using a calibrated spectrophotometer, as well as total transmittance
      measurements using a luxmeter. The results show that both types of marble
      transmit light and that Pentelic marble has a higher transmittance in the visible
      range than Paros marble in some cases and hence could have been one reason, among
      others, to change the type of marble in the roof in antiquity. 

PMID- 25967834
TI  - Measurements of skylight polarization: a case study in urban region with high
      loading aerosol.
AB  - We investigate skylight polarization patterns in an urban region using our
      developed full-Stokes imaging polarimeter. A detailed description of our imaging
      polarimeter and its calibration are given, then, we measure skylight polarization
      patterns at wavelength lambda=488  nm and at solar elevation between -05 degrees
      10' and +35 degrees 42' in the city of Hefei, China. We show that in an urban
      region with high-loading aerosols: (1) the measured degree of linear polarization
      reaches the maximum near sunset, and large areas of unpolarized sky exist in the
      forward sunlight direction close to the Sun; (2) the position of neural points
      shifts from the local meridian plane and, if compared with a clear sky, alters
      the symmetrical characteristics of celestial polarization pattern; and (3) the
      observed circular polarization component is negligible.

PMID- 25967835
TI  - Photographic observation of a natural fifth-order rainbow.
AB  - A photograph has been obtained of a natural fifth-order (quinary) rainbow. The
      photograph was acquired on 8 August 2012 with a digital camera and a polarization
      filter to maximize contrast of the rainbows with the background. The quinary
      rainbow, together with its first supernumerary, appears in a contrast-enhanced
      version of the photograph as broad green and blue-violet color bands within
      Alexander's dark band between the primary and secondary rainbows. The red band of
      the quinary rainbow is obscured by the much brighter secondary rainbow. A
      comparison with a numerical simulation using the Debye series confirms that the
      color bands of the quinary rainbow appear at the expected location. The numerical
      simulation produces a good match with the photograph for a droplet radius of 0.46
      mm. The green band of the quinary rainbow is even faintly discernible in the
      unprocessed photograph, suggesting that under exceptional viewing conditions the
      green band of the quinary rainbow may be observed visually with the aid of a
      polarization filter. 

PMID- 25967836
TI  - Polarization and visibility of higher-order rainbows.
AB  - The degree of polarization of rainbows of order k with k>=3 is bounded in the
      interval [75%, 78%], where 75% is the limit for k->infinity. A polarization
      filter can improve the signal-to-background ratio of the third and fourth
      rainbows by a factor of 2, which may lift their visibilities in natural
      circumstances above the threshold of human visual perception. Under optimal
      circumstances, the latter may be true for the recently photographed green
      fingerprint of the fifth rainbow, even without the aid of a polarization filter.
      The prospects for observing the sixth rainbow are unclear. There exists a
      possibility that the signal of the natural seventh rainbow (appearing at 64
      degrees  from the Sun) may be separated from its background if photographed under
      perfect conditions through a polarization filter. 

PMID- 25967837
TI  - Role of dust in landscape brightness and color.
AB  - Scattering by microscopic particles renders virtually all dusty surfaces brighter
      than dust-free surfaces. Examples of surface brightening are demonstrated in the
      landscape and laboratory and explained theoretically using Mie theory
      calculations. The implications for landscape photography and remote sensing are
      discussed. 

PMID- 25967838
TI  - Re-visiting the atmospheric corona.
AB  - The atmospheric corona is a well-known diffraction phenomenon, typically seen as
      colored rings surrounding the Sun or Moon. In many respects, Fraunhofer
      diffraction provides a good explanation of the corona. As the angular sizes of
      the corona's rings are inversely proportional to the radius, r, of the spherical
      particles causing the corona, it should be easy to estimate the particle size
      from observations and photographs. Noting that some of the techniques commonly
      used for particle sizing based on diffraction theory can give misleading results
      for coronas caused by the scattering of sunlight, this paper uses Mie theory
      simulations to demonstrate that the inner 3 red rings of the corona have angular
      radii of theta~16/r, 31/r, and 47/r, when theta is measured in degrees and r is
      measured in MUm. 

PMID- 25967839
TI  - 35 minute green flash observed at Little America on 16 October 1929: a
      retrospective study.
AB  - On 16 October 1929 five members of the Byrd Expedition 1 observed an intermittent
      35 min green flash at the Little America station (latitude -78.57 degrees ) in
      Antarctica. The flash was the result of strong atmospheric refraction, likely
      associated with a subcritical Novaya Zemlya mirage. This paper examines the
      constraints placed on the observation by the Earth-Sun orbital kinematics. It is
      found that the length of the observation cannot be explained solely by the
      slowness of the setting rate of the Sun, nor the time required just before the
      beginning of the Antarctic summer for the top of the Sun to set, reach its
      relative minimum position at the horizon, and then rise back up again. The
      observed length of the effect, however, is consistent with the Sun effectively
      setting twice and rising twice during the observation, with the first effective
      rising being the result of the observers climbing up the radio towers at the
      Little America station in order to keep the top of the Sun in view. 

PMID- 25967840
TI  - Infrared Moon imaging for remote sensing of atmospheric smoke layers.
AB  - Simultaneous visible and long-wave infrared (IR) images of the Moon were used
      with a simple energy-balance model to study the spatial pattern of lunar surface
      temperatures. The thermal images were obtained with a radiometrically calibrated,
      compact, low-cost, commercial IR camera mounted on a small telescope. Differences
      between the predicted and measured maximum Moon temperatures were used to
      determine the infrared optical depth (OD), which represents the path-integrated
      extinction of an elevated layer of wildfire smoke in the atmosphere. The OD
      values retrieved from the IR Moon images were combined with simultaneous OD
      measurements from a ground-based, zenith-pointing lidar operating at a wavelength
      of 532 nm to determine an IR-to-visible OD ratio of 0.50+/-0.18 for moderately
      aged wildfire smoke aerosol. 

PMID- 25967841
TI  - Visible and invisible mirages: comparing inferior mirages in the visible and
      thermal infrared.
AB  - Visible (VIS)-light and thermal infrared (IR) inferior mirages in the 8-14 MUm
      waveband have been observed simultaneously for the takeoff and landing of various
      airplanes at distances of several kilometers. Similarities as well as differences
      between the VIS and IR mirages are discussed. 

PMID- 25967842
TI  - Snell's window in wavy water.
AB  - The angular diameter of Snell's window as a function of maximum wave slope is
      calculated. For flat water the diameter is 97 degrees  and increases up to about
      122 degrees  when the wave slope is about 16 degrees . Steeper waves break and
      disrupt the smooth surface used in the analysis. Breaking waves produce a window
      almost 180 degrees  wide. The brightness of the dark area around Snell's window
      is heavily influenced by turbidity and upwelling radiation, especially in shallow
      water. 

PMID- 25967843
TI  - Downwelling spectral irradiance during evening twilight as a function of the
      lunar phase.
AB  - We measured downwelling spectral vector irradiance (from 350 to 800 nm) during
      evening civil and nautical twilight (solar elevation down to -12 degrees ). Nine
      sets of measurements were taken to cover the first half of the lunar cycle (from
      the new to full moon) and were also used to calculate chromaticity (CIE 1976
      u'v'). The lunar phase had no consistent effect on downwelling irradiance until
      solar elevation was less than -8 degrees . For lower solar elevations, the effect
      of the moon increased with the fraction of the illuminated lunar disk until the
      fraction was approximately 50%. For fractions greater than 50%, the brightness
      and chromaticity of the downwelling irradiance were approximately independent of
      the fraction illuminated, likely because the greater brightness of a fuller moon
      was offset by its lower elevation during twilight. Given the importance of
      crepuscular periods to animal activity, including predation, reproductive cycles,
      and color vision in dim light, these results may have significant implications
      for animal ecology.

PMID- 25967844
TI  - Probable photographic detection of the natural seventh-order rainbow.
AB  - We present a stacked and contrast-enhanced image comprised of 12 digital
      photographs that shows a series of color hues in the correct order and location
      to be part of the seventh-order rainbow. The observation was made on September
      22, 2013, near Magdalena in New Mexico (USA). The seventh-order rainbow is
      located at 64 degrees  from the Sun in a region of the sky with little
      interference from the zero-order glow. The color hues in the image range from red
      to blue-violet, spanning about 12 degrees  in total extent; their locations
      generally agree with a numerical Debye-series simulation of the seventh-order
      rainbow. Despite the low color contrast of the seventh-order rainbow, the current
      observation indicates that it is feasible with current digital-imaging technology
      to detect this higher-order rainbow in near-ideal atmospheric conditions. 

PMID- 25967846
TI  - I Am Happy To Be Here (So Giving Thanks)!: editorial.

PMID- 25967845
TI  - Artificially generated halos: rotating sample crystals around various axes.
AB  - So far experiments with artificial halos from single transparent crystals have
      suffered from the lack of apparatus that allows simultaneous rotation around two
      and three axes. A new setup is presented which overcomes these restrictions by
      combining electrical as well as pneumatic concepts. This enables reproducible
      experiments of the most common halos observed in nature and for the first time
      artificial ring halos from single hexagons rotating around three axes
      simultaneously. In addition, an old qualitative halo demonstration based on
      perceived colors of rotating colored areas whose contours represent scattering
      plots has been reinvestigated and the usually nonsaturated color of artificial
      parhelia was visualized using a crossed prism method. These new experiments are
      discussed in the context of all known artificial halo experiments. 

PMID- 25967847
TI  - Light and color in the open air: Introduction to the feature issue.
AB  - This is a feature issue devoted to optical phenomena in nature. Many of the
      papers published in this feature issue are based on presentations given at the
      "Light & Color in Nature" conference held in August 2013 at the University of
      Alaska-Fairbanks. 

PMID- 25967848
TI  - Effects of the Peroxisome Proliferator-Activated Receptor-gamma Agonist
      Pioglitazone on Peripheral Vessel Function and Clinical Parameters in Nondiabetic
      Patients: A Double-Center, Randomized Controlled Pilot Trial.
AB  - OBJECTIVE: Despite the advanced therapy with statins, antithrombotics, and
      antihypertensive agents, the medical treatment of atherosclerotic disease is less
      than optimal. Therefore, additional therapeutic antiatherosclerotic options are
      desirable. This pilot study was performed to assess the potential antiatherogenic
      effect of the peroxisome proliferator-activated receptor-gamma agonist
      pioglitazone in nondiabetic patients. METHODS: A total of 54 nondiabetic patients
      were observed in a prospective, double-blind, placebo-controlled study. Patients
      were randomized to pioglitazone or placebo. The following efficacy parameters
      were determined by serial analyses: artery pulse wave analysis and carotid
      femoral pulse wave velocity (PWV), static and dynamic retinal vessel function,
      and the common carotid intima-media thickness (IMT). The main secondary endpoint
      was the change in different biochemical markers. RESULTS: After 9 months, no
      relevant differences could be determined in the two treatment groups in PWV
      (pioglitazone 14.3 +/- 4.4 m/s vs. placebo 14.2 +/- 4.2 m/s), retinal arterial
      diameter (pioglitazone 112.1 +/- 23.3 um vs. placebo 117.9 +/- 21.5 um) or IMT
      (pioglitazone 0.85 +/- 0.30 mm vs. placebo 0.79 +/- 0.15 mm). Additionally, there
      were no differences in the change in biochemical markers like cholesteryl ester
      transfer protein, low-density lipoprotein cholesterol, high-sensitivity C
      reactive protein or white blood cell count. CONCLUSIONS: Treatment with a
      peroxisome proliferator-activated receptor-gamma agonist in nondiabetic patients
      did not improve the function of large and small peripheral vessels (PPP Trial,
      clinicaltrialsregister.eu: 2006-000186-11).

PMID- 25967849
TI  - Androgenic control of male-typical behavior, morphology and sex recognition is
      independent of the mode of sex determination: A case study on Lichtenfelder's
      gecko (Eublepharidae: Goniurosaurus lichtenfelderi).
AB  - Previous work on lizards has shown that many sexually dimorphic traits depend on
      testosterone (T), but the details of this control can vary among species. Here,
      we tested the role of T on the expression of morphological, physiological, and
      behavioral traits in Lichtenfelder's gecko (Goniurosaurus lichtenfelderi), from
      the lizard family Eublepharidae notable for interspecific variation in sexually
      dimorphic traits and the mode of sex determination. Experiments included three
      groups of males (intact control, surgically castrated, castrated with T
      replacement) and two groups of females (intact control, T supplemented). In
      males, castration caused reductions in 1) the size of hemipenes, 2) offensive
      aggression, 3) male sexual behavior in a neutral arena, 4) activity of precloacal
      glands, and 5) loss of male chemical cues for sex recognition. These reductions
      were not observed in castrated males with T replacement. Interestingly, castrated
      males performed sexual behavior in their home cages, which shows that the effect
      of T depends on the environmental context. Notably, tail vibration, previously
      reported as a courtship behavior in other eublepharids, is displayed by males of
      G. lichtenfelderi during interactions with conspecifics of both sexes, suggesting
      an evolutionary shift in the meaning of this signal. In females, T induced growth
      of hemipenes and male-typical courtship but did not induce precloacal pore
      activity, aggression, or mounting. In comparison to previous reports on
      Eublepharis macularius, our results indicate that effects of T do not depend on
      the mode of sex determination. Further, our results extend our understanding of
      the complexity of control of male traits and illustrate how lability in the
      effects of T can be a general mechanism causing evolutionary changes in the
      components of suites of functionally correlated traits. 

PMID- 25967850
TI  - Medicine's perception of reality - a split picture: critical reflections on
      apparent anomalies within the biomedical theory of science.
AB  - Escalating costs, increasing multi-morbidity, medically unexplained health
      problems, complex risk, poly-pharmacy and antibiotic resistance can be regarded
      as artefacts of the traditional knowledge production in Western medicine, arising
      from its particular worldview. Our paper presents a historically grounded
      critical analysis of this view. The materialistic shift of Enlightenment
      philosophy, separating subjectivity from bodily matter, became normative for
      modern medicine and yielded astonishing results. The traditional dichotomies of
      mind/body and subjective/objective are, however, incompatible with modern
      biological theory. Medical knowledge ignores central tenets of human existence,
      notably the physiological impact of subjective experience, relationships, history
      and sociocultural contexts. Biomedicine will not succeed in resolving today's
      poorly understood health problems by doing 'more of the same'. We must
      acknowledge that health, sickness and bodily functioning are interwoven with
      human meaning-production, fundamentally personal and biographical. This implies
      that the biomedical framework, although having engendered 'success stories' like
      the era of antibiotics, needs to be radically revised. 

PMID- 25967851
TI  - Natural history of dental caries in very young Australian children.
AB  - BACKGROUND: Whilst the global burden of caries is increasing, the trajectory of
      decay in young children and the point at which prevention should occur has not
      been well established. AIM: To identify the 'natural history' of dental caries in
      early childhood. DESIGN: A birth cohort study was established with 467
      mother/child dyads followed at 1, 6, 12, 18, and 36 months of age. Parent
      completed surveys captured demographic, social, and behavioural data, and oral
      examinations provided clinical and data. RESULTS: Eight per cent of children (95%
      confidence interval (CI): 5-12%) at 18 months and 23% (95% CI: 18-28%) at 36
      months experienced decay. Interesting lesion behaviour was found between 18 and
      36 months, with rapid development of new lesions on sound teeth (70% of teeth,
      95% CI: 63-76%) and regression of many lesions from non-cavitated lesions to
      sound (23% of teeth, 95% CI: 17-30%). Significant associations were found between
      soft drink consumption and lesion progression. CONCLUSIONS: Findings suggest
      optimal time periods for screening and prevention of a disease which
      significantly impacts multiple health and well-being outcomes across the life
      course.

PMID- 25967852
TI  - Efficacy and safety of uterine manipulators in laparoscopic surgery: a review.
AB  - PURPOSE: This review aims to objectively assess the efficacy and safety of
      uterine manipulators as reported in scientific literature. Furthermore, it
      evaluates as to which manipulator best suits which surgical procedure. METHODS:
      PubMed, Embase, Web of Science, COCHRANE, CINAHL, Academic Search Premier,
      Science Direct and the MAUDE database were searched. Technical information was
      retrieved from the manufacturers. RESULTS: 25 articles covering 10 uterine
      manipulators were found. Studies regarding implementation and use of manipulators
      are scarce; only two surveys were found comparing different manipulators.
      Moreover, clinical evidence proving the efficacy of manipulators with respect to
      prevention of complications, inherent to laparoscopic surgery, does not exist.
      CONCLUSION: The use of uterine manipulators is well established and it is clear
      that uterine manipulators offer the easiest way to handle the uterus during
      surgery. However, detailed information regarding efficacy and safety is scarce.
      Clinical evidence substantiating the assumed mechanism of prevention of ureter
      injuries was not found. Our review did not find the optimal manipulator. Some are
      more versatile than others and not all instruments are appropriate for all types
      of surgery. Therefore, gynecologists should choose the manipulator that best
      suits the type of surgery that is performed.

PMID- 25967853
TI  - Lower Extremity Limb Salvage After Trauma: Versatility of the Anterolateral Thigh
      Free Flap.
AB  - OBJECTIVES: To compare the outcomes and complications of the anterolateral thigh
      free flap (ALT FF) versus other free muscle flaps for reconstruction of traumatic
      defects of the lower extremity. DESIGN: Retrospective review from a single
      plastic and reconstructive surgical unit comparing outcomes between 2 free flap
      groups-ALT FF and other commonly used muscle free flaps. SETTING: Tertiary
      referral University Hospital Level I Trauma Center. PATIENTS: Hundred patients
      who underwent lower extremity salvage for traumatic injuries. INTERVENTION: Free
      flap coverage of traumatic lower extremity injuries. MAIN OUTCOMES MEASUREMENTS:
      Successful for limb salvage, intraoperative and postoperative complications. DATA
      SYNTHESIS: Categorical variables were analyzed using chi and Fisher exact tests;
      continuous variables were examined using Wilcoxon rank-sum test. CONCLUSIONS: The
      ALT FF is equivalent in success to other traditional nonfasciocutaneous free
      flaps but may provide a more durable supple coverage with all components of the
      native soft-tissue envelop that can be tailored to the reconstructive needs of
      the traumatized lower extremity. Limb salvage outcomes may still be heavily
      influenced by the original severity of injury. LEVEL OF EVIDENCE: Therapeutic
      Level III. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 25967854
TI  - Influence of Fracture Stability on Early Patient Mortality and Reoperation After
      Pertrochanteric and Intertrochanteric Hip Fractures.
AB  - OBJECTIVES: To determine the influence of fracture stability on early patient
      mortality and complications requiring reoperation after trochanteric hip
      fracture. DESIGN: Prospective consecutive cohort study. SETTING: The orthopaedic
      unit of a public teaching hospital. PARTICIPANTS: Seven hundred twenty-eight
      patients with 743 consecutive stable (n = 446) pertrochanteric and unstable (n =
      297) pertrochanteric or intertrochanteric fractures (median age: 84 years, 71%
      females) resulting from a low-impact injury and surgically managed. Mean follow
      up of surviving patients was 4 years (range: 2-6 years). INTERVENTION: Fracture
      fixation by dynamic hip screw extramedullary device or intramedullary nail
      (Austofix or Gamma3) based on surgeon preference. MAIN OUTCOME MEASURES:
      Mortality within 6 and 12 months and surgical complications requiring device
      reoperation within 12 months of surgery (multivariate logistic regression and
      Kaplan-Meier survival analyses). RESULTS: Patients with unstable fractures were
      at 1.61 times (95% confidence interval: 1.18-2.21, P = 0.003) and 1.37 times (95%
      confidence interval: 1.02-1.83, P = 0.037) greater odds of dying within 6 and 12
      months, respectively, than those with stable fractures. Older age, male gender,
      higher American Society of Anesthesiologists classification, in residential care,
      and inpatient-reported medical complications were also independent risk factors
      for early mortality. Increasing fracture instability and fixation using the
      Austofix nail were associated with early device reoperation. Comparable results
      were reported for the dynamic hip screw and Gamma3 nail, although the Gamma3 nail
      may offer advantages for more complex unstable fractures. CONCLUSIONS: Fracture
      instability influences early mortality after surgical fixation of trochanteric
      hip fracture. The Austofix double lag screw device had suboptimal results. LEVEL
      OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 25967855
TI  - Percutaneous and Mucocutaneous Exposure Among Orthopaedic Surgeons: Immediate
      Management and Compliance With CDC Protocol.
AB  - BACKGROUND: Orthopaedic surgeons are at a high risk of sustaining a percutaneous
      or mucocutaneous exposure to blood and body fluids. The Center for Disease
      Control and Prevention recommends a wash with soap and water and notification of
      the concerned hospital authorities after any percutaneous/mucocutaneous exposure,
      but a systematic amenability with these guidelines is not always seen. This cross
      sectional study was undertaken to determine current knowledge and practices of
      orthopaedic surgeons in case of a percutaneous sharp injury exposure, emphasizes
      the immediate first aid steps taken after an exposure, the degree of reporting,
      and to explore the reasons for noncompliance. Finally, we sought to create
      awareness about the prevailing Center for Disease Control and Prevention
      guidelines after any exposure to blood or body fluids. MATERIALS AND METHODS: We
      conducted a cross-sectional survey using an anonymous prepared questionnaire. The
      study population included exclusively orthopaedic surgeons, including residents,
      fellows, and attending physicians at 4 US institutions. The questionnaire was
      also available online on the OTA Web site as a part of survey monkey. The
      questionnaire comprised 9 multiple choice questions, and more than 1 response
      could be given for some questions. The questions addressed previous needle
      stick/sharp injury exposure, number of times that had happened, whether reported
      to the hospital administration, reason for nonreporting, and risk perception for
      transmission of blood-borne pathogens (human immunodeficiency virus, HBsAg, and
      hepatitis C virus). The questions were also asked based on what should be done in
      four different clinical settings based on respondents risk perception. RESULTS:
      Of fifty eight attendings, 7 fellows, 45 residents, and 7 respondents who did not
      indicate their position participated in the survey for a total of 117
      respondents. Out of 99, 24 had sustained it once, 18 twice, 11 three times, and
      35 at least 4 times. When questioned about informing the incident to the hospital
      administration, 38% had always reported the incident, 33% had never reported the
      incident, and the remaining 29% had not reported it every time. Of note, 87% gave
      the correct response about the risk of transmission of human immunodeficiency
      virus after an exposure. On questioning about the risk of hepatitis B
      transmission, from an HBsAg- and HBeAg-positive source, 13% gave the correct
      response, whereas from HBsAg-positive and HBeAg-negative source, 30% gave the
      correct response. Regarding transmission of hepatitis C virus from a positive
      source, 36% responded correctly. The surgeons seemingly attempted to risk
      stratify their exposure, and they were more likely to report their exposure in
      the higher risk scenarios. CONCLUSIONS: This study demonstrates that orthopaedic
      surgeons of all levels of training are at high risk of occupational exposure to
      blood-borne pathogens. Moreover, despite the level of training, the majority of
      surgeons do not follow the recommended steps, although we do not know the reasons
      for such behavior. Also, there is a low awareness of the significant risk of
      hepatitis transmission among orthopaedic surgeons treating a population with a
      high prevalence of undiagnosed hepatitis.

PMID- 25967856
TI  - Neurologic Injury in Operatively Treated Acetabular Fractures.
AB  - OBJECTIVES: The purpose of this study is to evaluate a series of operatively
      treated acetabular fractures with neurologic injury and to track sensory and
      motor recovery. METHODS: Operatively treated acetabular fractures with neurologic
      injury from 8 trauma centers were reviewed. Patients were followed for at least 6
      months or to neurologic recovery. Functional outcome was documented at 3 months,
      6 months, and final follow-up. Outcomes included motor and sensory recovery,
      brace use, development of chronic regional pain syndrome, and return to work.
      RESULTS: One hundred thirty-seven patients (101 males and 36 females), average
      age 42 (17-87) years, met the criteria. Mechanism of injury included MVC (67%),
      fall (11%), and other (22%). The most common fracture types were transverse +
      posterior wall (33%), posterior wall (23%), and both-column (23%). Deficits were
      identified as preoperative in 57%, iatrogenic in 19% (immediately after surgery),
      and those that developed postoperatively in 24%. A total of 187 nerve deficits
      associated with the following root levels were identified: 7 in L2-3, 18 in L4,
      114 in L5, and 48 in S1. Full recovery occurred in 54 (29%), partial recovery in
      69 (37%), and 64 (34%) had no recovery. Forty-three percent of S1 deficits and
      29% of L5 deficits had no recovery. Fifty-five percent of iatrogenic injuries did
      not recover. Forty-eight patients wore a brace at the final follow-up, all for an
      L5 root level deficit. Although 60% (42/70) returned to work, chronic regional
      pain syndrome was seen to develop in 19% (18/94). CONCLUSIONS: Peripheral
      neurologic injury in operatively treated acetabular fractures occurs most
      commonly in the sciatic nerve distribution, with L5 root level deficits having
      only a 26% chance of full recovery. LEVEL OF EVIDENCE: Prognostic Level IV. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 25967858
TI  - Successful Management of a Unique Condition of Isolated Intracranial Mucormycosis
      in an Immunocompetent Child.
AB  - This report describes a unique case of isolated intracranial mucormycosis of a
      slowly progressive nature in a healthy immunocompetent child. A 4-year-old girl
      with a clear medical and surgical history presented with complaints of right side
      facial asymmetry and unsteady gait for a period of 10 months. Clinical and
      radiographic investigations revealed right-sided lower motor neuron facial palsy
      caused by an infiltrative lesion on the right cerebellopontine angle. Initial
      surgical debulking was performed, a biopsy was sent for histopathological
      examination, and a course of prophylactic antibiotic and antifungal drugs was
      prescribed. The pathological report confirmed the mucormycosis fungal infection,
      and intravenous amphotericin B was administered for 3 weeks. One month after
      admission, the patient left the hospital with complete recovery. Follow-ups after
      4, 8 and 12 weeks revealed no sensory or motor neurological deficits. In
      conclusion, this is a unique case of mucormycosis with regard to the nature and
      location of the infection, along with the host being a healthy child. Initial
      surgical exploration is a very critical step in the early diagnosis and treatment
      of such rare conditions.

PMID- 25967860
TI  - The shock society officers of the society 2014-2015.

PMID- 25967857
TI  - Enhanced differentiation of intraepithelial lymphocytes in the intestine of
      polymeric immunoglobulin receptor-deficient mice.
AB  - To clarify the effect of secretory IgA (sIgA) deficiency on gut homeostasis, we
      examined intraepithelial lymphocytes (IELs) in the small intestine (SI) of
      polymeric immunoglobulin receptor-deficient (pIgR(-/-) ) mice. The pIgR(-/-) mice
      exhibited the accumulation of CD8alphabeta(+) T-cell receptor (TCR)-alphabeta(+)
      IELs (CD8alphabeta(+) alphabeta-IELs) after weaning, but no increase of
      CD8alphabeta(+) gammadelta-IELs was detected in pIgR(-/-) TCR-beta(-/-) mice
      compared with pIgR(+/+) TCR-beta(-/-) mice. When 5-bromo-2'-deoxyuridine (BrdU)
      was given for 14 days, the proportion of BrdU-labelled cells in SI-IELs was not
      different between pIgR(+/+) mice and pIgR(-/-) mice. However, the proportion of
      BrdU-labelled CD8alphabeta(+) -IELs became higher in pIgR(-/-) mice than
      pIgR(+/+) mice 10 days after discontinuing BrdU-labelling. Intravenously
      transferred splenic T cells migrated into the intraepithelial compartments of
      pIgR(+/+) TCR-beta(-/-) mice and pIgR(-/-) TCR-beta(-/-) mice to a similar
      extent. In contrast, in the case of injection of immature bone marrow cells,
      CD8alphabeta(+) alphabeta-IELs increased much more in the SI of pIgR(-/-) TCR
      beta(-/-) mice than pIgR(+/+) TCR-beta(-/-) mice 8 weeks after the transfer.
      alphabeta-IELs from pIgR(-/-) mice could produce more interferon-gamma and
      interleukin-17 than those of pIgR(+/+) mice, and intestinal permeability tended
      to increase in the SI of pIgR(-/-) mice with aging. Taken together, these results
      indicate that activated CD8alphabeta(+) alphabeta-IELs preferentially accumulate
      in pIgR(-/-) mice through the enhanced differentiation of immature haematopoietic
      precursor cells, which may subsequently result in the disruption of epithelial
      integrity.

PMID- 25967859
TI  - Altering the Position of Phenyl Substitution to Adjust Film Morphology and Memory
      Device Performance.
AB  - In this study, two structural isomers alpha-PBT and beta-PBT, which only differ
      in the phenyl substituent position on the quinoline chromophore, have been
      designed and successfully synthesized. The influences of substituent position on
      the film morphology and the storage performance of the devices were investigated.
      Both molecules employed in the memory devices exhibited same nonvolatile binary
      (write-once-read-many-times; WORM) characteristics, but the switch threshold
      voltage (Vth) of the beta-PBT-based device was clearly lower than that of the
      alpha-PBT-based device. Simulation results demonstrate that the variation of the
      phenyl substituent position led to different intermolecular stacking styles and
      thus to varied grain sizes for each film morphology. This work illustrates that
      altering the phenyl substituent position on the molecular backbone could improve
      the quality of the film morphology and reduce power consumption, which is good
      for the rational design of future advanced organic memory devices (OMDs). 

PMID- 25967861
TI  - SHOCK SOCIETY THIRTY-EIGHTH ANNUAL CONFERENCE ON SHOCK: Grand Hyatt Denver
      Denver, Colorado June 6 - 9, 2015.

PMID- 25967863
TI  - Heartbeat: Focus on atrial fibrillation.

PMID- 25967864
TI  - The BCS Annual Conference, Manchester, 8-10 June 2015. The vice-president's
      message.

PMID- 25967865
TI  - Acute hemodynamic deterioration during permanent pacemaker implantation. Air
      embolism.

PMID- 25967866
TI  - Carbon-Coated Core-Shell Fe-Cu Nanoparticles as Highly Active and Durable
      Electrocatalysts for a Zn-Air Battery.
AB  - Understanding the interaction between a catalyst and oxygen has been a key step
      in designing better electrocatalysts for the oxygen reduction reaction (ORR) as
      well as applying them in metal-air batteries and fuel cells. Alloying has been
      studied to finely tune the catalysts' electronic structures to afford proper
      binding affinities for oxygen. Herein, we synthesized a noble-metal-free and
      nanosized transition metal CuFe alloy encapsulated with a graphitic carbon shell
      as a highly efficient and durable electrocatalyst for the ORR in alkaline
      solution. Theoretical models and experimental results demonstrated that the CuFe
      alloy has a more moderate binding strength for oxygen molecules as well as the
      final product, OH(-), thus facilitating the oxygen reduction process.
      Furthermore, the nitrogen-doped graphitic carbon-coated layer, formed
      catalytically under the influence of iron, affords enhanced charge transfer
      during the oxygen reduction process and superior durability. These benefits were
      successfully confirmed by realizing the catalyst application in a mechanically
      rechargeable Zn-air battery. 

PMID- 25967867
TI  - High-activity PtRuPd/C catalyst for direct dimethyl ether fuel cells.
AB  - Dimethyl ether (DME) has been considered as a promising alternative fuel for
      direct-feed fuel cells but lack of an efficient DME oxidation electrocatalyst has
      remained the challenge for the commercialization of the direct DME fuel cell. The
      commonly studied binary PtRu catalyst shows much lower activity in DME than
      methanol oxidation. In this work, guided by density functional theory (DFT)
      calculation, a ternary carbon-supported PtRuPd catalyst was designed and
      synthesized for DME electrooxidation. DFT calculations indicated that Pd in the
      ternary PtRuPd catalyst is capable of significantly decreasing the activation
      energy of the C?O and C?H bond scission during the oxidation process. As
      evidenced by both electrochemical measurements in an aqueous electrolyte and
      polymer-electrolyte fuel cell testing, the ternary catalyst shows much higher
      activity (two-fold enhancement at 0.5 V in fuel cells) than the state-of-the-art
      binary Pt50 Ru50 /C catalyst (HiSPEC 12100). 

PMID- 25967869
TI  - Useful agents against aflatoxin B1 - antibacterial azomethine and Mn(III)
      complexes involving L-Threonine, L-Serine, and L-Tyrosine.
AB  - The present study is focused on evaluating the antimutagenic properties of Schiff
      bases and Mn(III) complexes with L-Threonine, L-Serine and L-Tyrosine, which have
      antimicrobial activity. These six compounds were investigated for antimutagenic
      properties against Aflatoxin Bi (AFBi) by the micronucleus (MN) assay in a human
      lymphocyte cell culture in vitro. The protective role of these compounds against
      AFBi-induced MN is probably related to its doses. A mechanism has been proposed
      to reduce the effect of AFBi. 

PMID- 25967868
TI  - A multicentre comparison of quantitative (90)Y PET/CT for dosimetric purposes
      after radioembolization with resin microspheres : The QUEST Phantom Study.
AB  - PURPOSE: To investigate and compare the quantitative accuracy of (90)Y imaging
      across different generation PET/CT scanners, for the purpose of dosimetry after
      radioembolization with resin microspheres. METHODS: A strict experimental and
      imaging protocol was followed by 47 international sites using the NEMA 2007/IEC
      2008 PET body phantom with an 8-to-1 sphere-to-background ratio of (90)Y
      solution. The phantom was imaged over a 7-day period (activity ranging from 0.5
      to 3.0 GBq) and all reconstructed data were analysed at a core laboratory for
      consistent processing. Quantitative accuracy was assessed through measures of
      total phantom activity, activity concentration in background and hot spheres,
      misplaced counts in a nonradioactive insert, and background variability. RESULTS:
      Of the 69 scanners assessed, 37 had both time-of-flight (ToF) and resolution
      recovery (RR) capability. These current generation scanners from GE, Philips and
      Siemens could reconstruct background concentration measures to within 10% of true
      values over the evaluated range, with greater deviations on the Philips systems
      at low count rates, and demonstrated typical partial volume effects on hot sphere
      recovery, which dominated spheres of diameter <20 mm. For spheres >20 mm in
      diameter, activity concentrations were consistently underestimated by about 20%.
      Non-ToF scanners from GE Healthcare and Siemens were capable of producing
      accurate measures, but with inferior quantitative recovery compared with ToF
      systems. CONCLUSION: Current generation ToF scanners can consistently reconstruct
      (90)Y activity concentrations, but they underestimate activity concentrations in
      small structures (<=37 mm diameter) within a warm background due to partial
      volume effects and constraints of the reconstruction algorithm. At the highest
      count rates investigated, measures of background concentration (about 300 kBq/ml)
      could be estimated on average to within 1%, 5% and 2% for GE Healthcare (all-pass
      filter, RR + ToF), Philips (4i8s ToF) and Siemens (2i21s all-pass filter, RR +
      ToF) ToF systems, respectively. Over the range of activities investigated,
      comparable performance between GE Healthcare and Siemens ToF systems suggests
      suitability for quantitative analysis in a scenario analogous to that of
      postradioembolization imaging for treatment of liver cancer.

PMID- 25967871
TI  - Using Next-Generation Sequencing to Identify a Mutation in Human MCSU that is
      Responsible for Type II Xanthinuria.
AB  - BACKGROUND: Hypouricemia is caused by various diseases and disorders, such as
      hepatic failure, Fanconi renotubular syndrome, nutritional deficiencies and
      genetic defects. Genetic defects of the molybdoflavoprotein enzymes induce
      hypouricemia and xanthinuria. Here, we identified a patient whose plasma and
      urine uric acid levels were both extremely low and aimed to identify the
      pathogenic gene and verify its mechanism. METHODS: Using next-generation
      sequencing (NGS), we detected a mutation in the human molybdenum cofactor
      sulfurase (MCSU) gene that may cause hypouricemia. We cultured L02 cells, knocked
      down MCSU with RNAi, and then detected the uric acid and MCSU concentrations,
      xanthine oxidase (XOD) and xanthine dehydrogenase (XDH) activity levels, and
      xanthine/hypoxanthine concentrations in cell lysates and culture supernatants.
      RESULTS: The NGS results showed that the patient had a mutation in the human MCSU
      gene. The in vitro study showed that RNAi of MCSU caused the uric acid, human
      MCSU concentrations, the XOD and XDH activity levels among cellular proteins and
      culture supernatants to be extremely low relative to those of the control.
      However, the xanthine/hypoxanthine concentrations were much higher than those of
      the control. CONCLUSIONS: We strongly confirmed the pathogenicity of the human
      MCSU gene.

PMID- 25967870
TI  - Neuronal development is promoted by weakened intrinsic antioxidant defences due
      to epigenetic repression of Nrf2.
AB  - Forebrain neurons have weak intrinsic antioxidant defences compared with
      astrocytes, but the molecular basis and purpose of this is poorly understood. We
      show that early in mouse cortical neuronal development in vitro and in vivo,
      expression of the master-regulator of antioxidant genes, transcription factor NF
      E2-related-factor-2 (Nrf2), is repressed by epigenetic inactivation of its
      promoter. Consequently, in contrast to astrocytes or young neurons, maturing
      neurons possess negligible Nrf2-dependent antioxidant defences, and exhibit no
      transcriptional responses to Nrf2 activators, or to ablation of Nrf2's inhibitor
      Keap1. Neuronal Nrf2 inactivation seems to be required for proper development: in
      maturing neurons, ectopic Nrf2 expression inhibits neurite outgrowth and
      aborization, and electrophysiological maturation, including synaptogenesis. These
      defects arise because Nrf2 activity buffers neuronal redox status, inhibiting
      maturation processes dependent on redox-sensitive JNK and Wnt pathways. Thus,
      developmental epigenetic Nrf2 repression weakens neuronal antioxidant defences
      but is necessary to create an environment that supports neuronal development. 

PMID- 25967872
TI  - Quercetin Inhibits Pacemaker Potentials via Nitric Oxide/cGMP-Dependent
      Activation and TRPM7/ANO1 Channels in Cultured Interstitial Cells of Cajal from
      Mouse Small Intestine.
AB  - BACKGROUND: Quercetin regulates gastrointestinal (GI) motor activity but the
      molecular mechanism involved has not been determined. The authors investigated
      the effects of quercetin, a flavonoid present in various foods, on the pacemaker
      activities of interstitial cells of Cajal (ICCs) in murine small intestine in
      vitro and on GI motility in vivo. MATERIALS AND METHODS: Enzymatic digestion was
      used to dissociate ICCs from mouse small intestines. The whole-cell patch-clamp
      configuration was used to record pacemaker potentials in cultured ICCs in the
      absence or presence of quercetin and to record membrane currents of transient
      receptor potential melastatin (TRPM) 7 or transmembrane protein 16A (Tmem16A,
      anoctamin1 (ANO1)) overexpressed in human embryonic kidney (HEK) 293 cells. The
      in vivo effects of quercetin on GI motility were investigated by measuring the
      intestinal transit rates (ITRs) of Evans blue in normal mice. RESULTS: Quercetin
      (100-200 MUM) decreased the amplitudes and frequencies of pacemaker activity in a
      concentration-dependent manner in current clamp mode, but this action was blocked
      by naloxone (a pan-opioid receptor antagonist) and by GDPbetaS (a GTP-binding
      protein inhibitor). However, potassium channels were not involved in these
      inhibitory effects of quercetin. To study the quercetin signaling pathway, we
      examined the effects of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), an
      inhibitor of guanylate cyclase, and of RP-8-CPT-cGMPS, an inhibitor of protein
      kinase G (PKG). These inhibitors blocked the inhibitory effects of quercetin on
      pacemaker activities. Also, L-NAME (100 MUM), a non-selective NO synthase (NOS)
      inhibitor, blocked the effects of quercetin on pacemaker activity and quercetin
      stimulated cGMP production. Furthermore, quercetin inhibited both Ca(2+)
      activated Cl(-) channels (TMEM16A, ANO1) and TRPM7 channels. In vivo, quercetin
      (10-100 mg/kg, p.o.) decreased ITRs in normal mice in a dose-dependent manner.
      CONCLUSIONS: Quercetin inhibited ICC pacemaker activities by inhibiting TRPM7 and
      ANO1 via opioid receptor signaling pathways in cultured murine ICCs. The study
      shows quercetin attenuates GI tract motility, and suggests quercetin be
      considered the basis for the development of novel spasmolytic agents for the
      prevention or alleviation of GI motility dysfunctions.

PMID- 25967873
TI  - Effects of synthetic neural adhesion molecule mimetic peptides and related
      proteins on the cardiomyogenic differentiation of mouse embryonic stem cells.
AB  - BACKGROUND/AIMS: Pluripotent stem cells differentiating into cardiomyocyte-like
      cells in an appropriate cellular environment have attracted significant
      attention, given the potential use of such cells for regenerative medicine.
      However, the precise mechanisms of lineage specification of pluripotent stem
      cells are still largely to be explored. Identifying the role of various small
      synthetic peptides involved in cardiomyogenesis may provide new insights into
      pathways promoting cardiomyogenesis. METHODS: In the present study, using a
      transgenic murine embryonic stem (ES) cell lineage expressing enhanced green
      fluorescent protein (EGFP) under the control of alpha-myosin heavy chain (alpha
      MHC) promoter (palphaMHC-EGFP), we investigated the cardiomyogenic effects of 7
      synthetic peptides (Betrofin3, FGLs, FGL(L), hNgf_C2, EnkaminE, Plannexin and C3)
      on cardiac differentiation. The expression of several cardiac-specific markers
      was determined by RT-PCR whereas the structural and functional properties of
      derived cardiomyocytes were examined by immunofluorescence and electrophysiology,
      respectively. RESULTS: The results revealed that Betrofin3, an agonist of brain
      derived neurotrophic factor (BDNF) peptide exerted the most striking pro
      cardiomyogenic effect on ES cells. We found that BDNF receptor, TrkB expression
      was up-regulated during differentiation. Treatment of differentiating cells with
      Betrofin3 between days 3 and 5 enhanced the expression of cardiac-specific
      markers and improved cardiomyocyte differentiation and functionality as revealed
      by genes regulation, flow cytometry and patch clamp analysis. Thus Betrofin3 may
      exert its cardiomyogenic effects on ES cells via TrkB receptor. CONCLUSION: Taken
      together, the results suggest that Betrofin3 modulates BDNF signaling with
      positive cardiomyogenic effect in stage and dose-dependent manner providing an
      effective strategy to increase ES cell-based generation of cardiomyocytes and
      offer a novel therapeutic approach to cardiac pathologies where BDNF levels are
      impaired.

PMID- 25967875
TI  - Establishing assistant diagnosis models of solitary pulmonary nodules based on
      intelligent algorithms.
AB  - AIMS: This study aimed to establish an auxiliary diagnosis model for solitary
      pulmonary nodules (SPNs) and evaluate its test efficacy. METHODS: Three hundred
      thirty-two pathologically diagnosed SPN patients (186 malignant, 146 benign) were
      collected as subjects. The serum levels of 8 types of markers and 9 computed
      tomography (CT) imaging features of each patient were treated as independent
      variables. The corresponding pathological classification results (fungal
      inflammation, tuberculosis and tuberculoma, inflammatory pseudotumor, tumor
      middle differentiation, cancer) of quantized patients were treated as dependent
      variables. A 17-to-1 mathematical auxiliary SPN diagnosis model was established
      using a back propagation (BP) algorithm and a support vector machine (SVM)
      algorithm. A 40-case test set was used to estimate the effect. RESULTS: Two
      different auxiliary SPN diagnosis models were successfully established. The
      diagnostic accuracy, sensitivity and specificity of the BP algorithm diagnosis
      model were 60%, 68% and 46.7%, respectively, and those of the SVM algorithm model
      were 80%, 85.7% and 66.7%, respectively. CONCLUSION: The accuracy, sensitivity
      and specificity of the SVM diagnostic model were relatively high, indicating that
      the model has important reference value for determining the degree of SPN
      differentiation and is suitable for the auxiliary diagnosis of benign and
      malignant SPN.

PMID- 25967874
TI  - Resveratrol Attenuated Low Ambient Temperature-Induced Myocardial Hypertrophy via
      Inhibiting Cardiomyocyte Apoptosis.
AB  - BACKGROUND/AIMS: Low ambient temperature is an important risk factor for
      cardiovascular diseases, and has been shown to lead to cardiac hypertrophy. In
      this study, we aim to investigate if Resveratrol may inhibit cold exposure
      induced cardiac hypertrophy in mice, and if so to clarify its molecular
      mechanism. METHODS: Adult male mice were randomly assigned to Control group (kept
      at room temperature), Cold group (kept at low air temperature range from 3
      degrees C to 5 degrees C) and Resveratrol treatment group (100mg/kg/day) for
      eight weeks. HE staining, Masson staining and Transmission electron microscopy
      were employed to detect cardiac structure, fibrosis and myocardial
      ultrastructure, respectively. Echocardiogram was used to measure myocardial
      functions. Western blot was used to detect the expression of MAPK pathway and
      apoptotic proteins. TUENL assay was performed to evaluate cardiomyocyte
      apoptosis. qRT-PCR was employed to measure the mRNA level. RESULTS: Cold-treated
      mice showed a higher heart/body weight ratio and heart weight/tibia length ratio
      compared with control mice, and Resveratrol treatment may suppress these changes
      in cold-treated mice. Myocardial cross-section area and cardiac collagen volume
      were larger in cold group than control group, which also can be attenuated by
      Resveratrol treatment. Also, Resveratrol improved the ultrastructure damage of
      myocardium such as myofibril disarray in cold group. Echocardiogram measurement
      showed that EF and FS values in cold group declined apparently as compared to
      control group, and Resveratrol may improve the reduction of heart functions. The
      expression of p-JNK, p-p38 and p-ERK relative to total JNK, p38 and ERK in cold
      group was not altered in cold group and Resveratrol group as compared to control
      group. Cold-treated mouse hearts also showed the upregulation of hypertrophy
      related miRNA-miR-328 but not miR-23a, and Resveratrol treatment can inhibit the
      increase of miR-328. Finally, Resveratrol treatment also may suppress apoptosis
      of myocardium in cold-treated mouse hearts via inhibiting Bax and caspase-3
      activation. CONCLUSION: In summary, low ambient temperature can cause enlarged
      heart, ultrastructure damage of myocardium and weakened functions, and
      Resveratrol treatment effectively suppressed these changes at least partially via
      inhibiting cardiomyocyte apoptosis.

PMID- 25967876
TI  - Angiotensin-(1-7) Attenuates Angiotensin II-Induced ICAM-1, VCAM-1, and MCP-1
      Expression via the MAS Receptor Through Suppression of P38 and NF-kappaB Pathways
      in HUVECs.
AB  - BACKGROUND/AIMS: Atherosclerosis is a chronic inflammatory disease. Intracellular
      adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1), and
      monocyte chemoattractant protein-1 (MCP-1) play important roles in inflammatory
      processes. P38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)
      kappaB signaling regulate ICAM-1, VCAM-1, and MCP-1 expression. Angiotensin (Ang)
      II upregulates ICAM-1, VCAM-1, and MCP-1 expression through the P38 MAPK and NF
      kappaB pathways. Ang-(1-7) may oppose the actions of Ang II. We investigated
      whether Ang-(1-7) prevents Ang II-induced ICAM-1, VCAM-1, and MCP-1 expression in
      human umbilical vein endothelial cells (HUVECs). METHODS: ICAM-1, VCAM-1, and MCP
      1 expression was estimated by real-time polymerase chain reaction (PCR) and
      enzyme-linked immunosorbent assay (ELISA); P38, NF-kappaB, and p-IkappaB-alpha
      expression was estimated by western blotting. RESULTS: Ang-(1-7) inhibited Ang II
      induced ICAM-1, VCAM-1, and MCP-1 expression and secretion in HUVECs. Ang II
      sharply increased P38 MAPK phosphorylation, which was inhibited by pretreatment
      with Ang-(1-7). Moreover, Ang-(1-7) significantly inhibited Ang II-induced
      IkappaB-alpha phosphorylation and NF-kappaB P65 nuclear translocation. The MAS
      receptor antagonist A-779 abolished the suppressive effects of Ang-(1-7).
      CONCLUSION: Ang-(1-7) attenuates Ang II-induced ICAM-1, VCAM-1, and MCP-1
      expression via the MAs receptor by suppressing the P38 and NF-kappaB pathways in
      HUVECs. Ang-(1-7) might delay the progression of inflammatory diseases, including
      atherosclerosis.

PMID- 25967878
TI  - Errata.

PMID- 25967877
TI  - Activation in M1 but not M2 Macrophages Contributes to Cardiac Remodeling after
      Myocardial Infarction in Rats: a Critical Role of the Calcium Sensing
      Receptor/NRLP3 Inflammasome.
AB  - AIMS: Macrophage (MPhi) infiltration during myocardial infarction (MI) amplifies
      cardiac inflammation and remodeling. We investigated whether activation of the
      NRLP3 inflammasome by a calcium sensing receptor (CaSR) in MPhi subsets
      contributes to cardiac remodeling following MI. METHODS AND RESULTS: Infiltrated
      MPhi exhibited biphasic activation after MI; M1MPhi peaked at MI 3d and decreased
      until MI 14d, whereas M2MPhi peaked at MI 7d and decreased at MI 14d as shown via
      immunohistochemistry. IL-1beta co-infiltrated with both M1MPhi and M2MPhi; IL
      1beta exhibited the same infiltrating tendency as M1MPhi, which was detected by
      immunohistochemistry. Increasing ventricular fibrosis was confirmed by Masson
      staining. CaSR and NLRP3 inflammasome in the MI group were upregulated in MPhi
      subsets in myocardium and peritoneal MPhi (p-MPhi) compared with the sham groups
      which were detected by immunofluorescence and western blotting. CaSR-activated
      NLRP3 inflammasome played a role in M1MPhi via PLC-IP3 but did not play a role in
      M2MPhi which were polarized by the THP-1 as shown by western blotting and
      intracellular calcium measurement. CaSR/NLRP3 inflammasome activation in M1MPhi
      led to the following effects: upregulated alpha-sma, MMP-2 and MMP-9, and
      collagen secretion; and downregulated TIMP-2 in cardiac fibroblasts via IL-1beta
      IL-1RI, which was detected by coculturing M1MPhi and cardiac fibroblasts.
      CONCLUSIONS: We suggest that the CaSR/NLRP3 inflammasome plays an essential role
      via the PLC-IP3 pathway in M1MPhi to promote cardiac remodeling post-MI in rats,
      including accelerated cardiac fibroblast phenotypic transversion, increased
      collagen and extracellular matrix (ECM) secretion; however, the CaSR/NLRP3
      inflammasome does not play a role in this process in M2MPhi.

PMID- 25967879
TI  - The relationship between repolarization parameters and serum electrolyte levels
      in patients with J wave syndromes.
AB  - BACKGROUND: Intravenous administration of magnesium (Mg(2+)) is effective for
      polymorphic ventricular tachycardia via homogenization of transmural ventricular
      repolarization. Mg(2+) likely plays some role in the heterogeneity of
      repolarization in J wave syndromes. OBJECTIVE: To investigate the relationship
      between the repolarization parameters and serum Mg(2+), potassium (K(+)), and
      calcium (Ca(2+)) levels in J wave syndromes. METHODS: Thirteen J-wave syndrome
      patients (Brugada and early repolarization [ER] syndromes), with documented
      episodes of ventricular fibrillation (VF), and 13 ER pattern (ERP) or Brugada
      type ECG patients were enrolled (25 males, mean age 48 +/- 15 years). The 12-lead
      ECG-derived parameters including the QT, QT dispersion (QTd), Tpeak-Tend (Tp-e)
      interval, Tp-e dispersion (Tp-ed), Tp-e/QT ratio, and activation recovery
      interval (ARI) dispersion were calculated; the correlations between these
      parameters and electrolytes including Mg(2+), K(+), and Ca(2+) were analyzed.
      RESULTS: Although there was no association between serum K(+) or Ca(2+) and QTd,
      there was a strong negative correlation between serum Mg(2+) and QTd in J wave
      syndrome patients with a history of VF (r = -0.715, p = 0.006). Also, there was a
      tendency for a negative correlation between Mg(2+) and Tp-ed or ARI dispersion in
      J wave syndrome patients with a history of VF (r = -0.513, p = 0.072 and r = 
      0.53, p = 0.063, respectively). On the other hand, in 13 patients with a Brugada
      type ECG or ERP, no correlation was observed between serum Mg(2+) and the QTd, Tp
      ed or ARI dispersion. CONCLUSION: Serum Mg(2+) may play an important role in the
      cardiac repolarization process in J wave syndromes.

PMID- 25967880
TI  - Magnesium and selected parameters of the non-enzymatic antioxidant and immune
      systems and oxidative stress intensity in the seminal plasma of fertile males.
AB  - INTRODUCTION: The present study investigated associations between environmental
      exposure to magnesium (Mg) and the levels of oxidative stress parameters and
      selected cytokines, and the antioxidant defense system in the seminal plasma of
      fertile males. MATERIALS AND METHODS: The study population consisted of 57
      healthy, non-smoking, fertile men from the southern region of Poland. Based on
      the median magnesium levels in seminal plasma, subjects were divided into two
      groups: those with low (Mg-L) and high (Mg-H) magnesium concentrations. RESULTS:
      Differences were not observed between the Mg-L and Mg-H groups as regards semen
      volume, pH, count, motility, or morphology of sperm cells. In the Mg-H group,
      cholesterol levels were significantly higher (77%) compared with the Mg-L group:
      however, gamma-glutamyltranspeptidase activity was significantly lower (21%). The
      values of total oxidant status were significantly different between the two
      groups, with 78% higher values observed in the Mg-H group compared with the Mg-L
      group, whereas malondialdehyde levels did not differ significantly. The values
      for total antioxidant capacity and uric acid levels were significantly lower in
      the Mg-H group compared with the Mg-L group (14% and 17%, respectively). However,
      levels of bilirubin, albumin, thiol groups and alpha-tocopherol were
      significantly higher in the Mg-H group (71%, 44%, 35% and 47%, respectively).
      CONCLUSION: No associations between Mg levels in the seminal plasma of fertile
      males and standard semen parameters were found. However, Mg levels may be
      associated with altered function of the non-enzymatic antioxidant system.

PMID- 25967881
TI  - Influence of extracellular magnesium on phagocytosis and free cytosolic Mg levels
      in differentiated U937 and MH-S cells.
AB  - BACKGROUND: The influence of extracellular calcium on phagocytosis is limited,
      and the involvement of extracellular magnesium is unclear. AIMS: The role of
      extracellular calcium and magnesium on phagocytosis efficiency was investigated.
      RESULTS: Extracellular calcium had no influence on the internalization of 1 MUm
      polystyrene particles by primary monocytes as has been shown before for the human
      lymphoma-derived, differentiated cell line U937 and murine alveolar macrophage
      derived MH-S cells. In contrast, the phagocytosis by differentiated U937 cells
      was positively affected by the presence of extracellular magnesium whereas that
      of MH-S cells was not. An extracellular increase in the magnesium level did not
      cause an increase in the free cytosolic magnesium concentration in either cell
      line. In contrast to magnesium, extracellular calcium caused an increase in
      intracellular divalent cation levels in differentiated U937 cells. CONCLUSIONS: A
      phagocytosis-enhancing effect in the extracellular space was observed in relation
      to extracellular magnesium rather than with an intracellular increase in
      magnesium levels, indicating that murine and human immune cells might be
      regulated differently.

PMID- 25967882
TI  - Magnesium protects against bile duct ligation-induced liver injury in male Wistar
      rats.
AB  - The aim of this study was to investigate the effects of magnesium sulfate (MgSO4)
      on cholestasis-induced hepatic injury after bile duct ligation (BDL) in male
      Wistar rats. In this study, the effects of 28-day, oral administration of MgSO4
      (at doses of 0.01, 0.05, 0.1, and 0.2 g/kg bw) were evaluated in normal and BDL
      induced cholestatic rats. The BDL group showed significant increases in serum
      levels of ALP, ALT, AST, GGT and significant decreases in hepatic SOD and
      catalase activities. BDL rats also had significant decreases in the serum levels
      of albumin, bilirubin, total cholesterol, triglycerides, and LDL. Administration
      of MgSO4 significantly attenuated these changes to nearly normal levels.
      Administrations of MgSO4 did not change these parameters in normal rats.
      Histopathological studies further confirmed the protective effects of MgSO4 on
      cholestasis-induced hepatic injury in the BDL rat model. Taken together, the
      results of this study suggest that MgSO4 treatment may be beneficial in
      cholestasis-induced hepatotoxicity.

PMID- 25967883
TI  - Versatile Electrochemical C-H Amination via Zincke Intermediates.
AB  - Simply by applying electricity, the amination reaction of a broad variety of
      arenes, heteroarenes, and benzylic substrates is achieved. Pyridine serves as the
      nitrogen source and the intermediate cationic species are well-protected from
      over-oxidation. 

PMID- 25967885
TI  - This edition includes 11 original articles covering an impressive wide range of
      topics. Introduction.

PMID- 25967886
TI  - The use of rugby scrum caps following parotidectomy to reduce the re-accumulation
      of seroma.

PMID- 25967887
TI  - Oral verrucous pre-malignant lesions and HPV.

PMID- 25967888
TI  - Comment on: Controversies in the management of sudden sensorineural hearing loss
      (SSNHL): an evidence based review.

PMID- 25967889
TI  - Ultrasound to locate the bone-anchored hearing aid cover screw for placement of
      the abutment at bone-anchored hearing aid second stage.

PMID- 25967890
TI  - Metabolic changes and factors influencing base deficit in infants undergoing
      craniosynostosis surgery: a retrospective study.
AB  - BACKGROUND: Corrective craniosynostosis surgery is often associated with a large
      amount of blood loss and metabolic disturbances. In the present study, we
      investigated the severity, duration of metabolic disturbances, and causal risk
      factors in infants. METHODS: A retrospective analysis was performed of 36 infants
      who underwent craniosynostosis surgery. We analyzed the following: demographics,
      duration of surgery, intraoperative blood loss, RBC, FFP and fluids transfused,
      urine output, hemodynamic parameters, and electrolyte and base deficit (BD)
      values. The lowest intraoperative BD value and time required (period I: <6 h;
      period II: 6-12 h; period III: >12 h) for BD values to return to normal (-4 to
      +2) in the postoperative period were determined. In addition, we recorded the
      postoperative length of stay in the ICU and hospital, postoperative blood loss,
      and early complications. RESULTS: We detected that 88% of the patients had
      subnormal BD levels and 22% had metabolic acidosis. The lowest average BD
      measured during the operation was -8.4 +/- 2.6 mmol/l. We carried out a multiple
      regression analysis, which revealed that lower BD values were associated with a
      longer duration of hypotension (p = 0.002, R(2) = 0.453) and greater
      intraoperative blood loss (p = 0.002, R(2) = 0.674). We examined the amount of
      intraoperative blood loss and found that that there were fewer blood product
      transfusions in period I patients and longer hypotensive episodes in period III
      patients. Also, a negative correlation was detected between the lowest
      intraoperative BD value with ICU duration (p = 0.004, r = -0.466) and hospital
      stay (p < 0.001, r = -0.764). CONCLUSION: Almost all patients developed
      intraoperative negative BD, which was prolonged in the postoperative period. The
      most important risk factors for developing negative BD are the amount of blood
      loss and duration of hypotension.

PMID- 25967891
TI  - Reshaping the epigenetic landscape during early flower development: induction of
      attractor transitions by relative differences in gene decay rates.
AB  - BACKGROUND: Gene regulatory network (GRN) dynamical models are standard systems
      biology tools for the mechanistic understanding of developmental processes and
      are enabling the formalization of the epigenetic landscape (EL) model. METHODS:
      In this work we propose a modeling framework which integrates standard
      mathematical analyses to extend the simple GRN Boolean model in order to address
      questions regarding the impact of gene specific perturbations in cell-fate
      decisions during development. RESULTS: We systematically tested the propensity of
      individual genes to produce qualitative changes to the EL induced by modification
      of gene characteristic decay rates reflecting the temporal dynamics of
      differentiation stimuli. By applying this approach to the flower specification
      GRN (FOS-GRN) we uncovered differences in the functional (dynamical) role of
      their genes. The observed dynamical behavior correlates with biological
      observables. We found a relationship between the propensity of undergoing
      attractor transitions between attraction basins in the EL and the direction of
      differentiation during early flower development - being less likely to induce up
      stream attractor transitions as the course of development progresses. Our model
      also uncovered a potential mechanism at play during the transition from EL basins
      defining inflorescence meristem to those associated to flower organs meristem.
      Additionally, our analysis provided a mechanistic interpretation of the homeotic
      property of the ABC genes, being more likely to produce both an induced inter
      attractor transition and to specify a novel attractor. Finally, we found that
      there is a close relationship between a gene's topological features and its
      propensity to produce attractor transitions. CONCLUSIONS: The study of how the
      state-space associated with a dynamical model of a GRN can be restructured by
      modulation of genes' characteristic expression times is an important aid for
      understanding underlying mechanisms occurring during development. Our
      contribution offers a simple framework to approach such problem, as exemplified
      here by the case of flower development. Different GRN models and the effect of
      diverse inductive signals can be explored within the same framework. We speculate
      that the dynamical role of specific genes within a GRN, as uncovered here, might
      give information about which genes are more likely to link a module to other
      regulatory circuits and signaling transduction pathways.

PMID- 25967892
TI  - Improved Visual Perception in Very Low Birth Weight Infants on Enhanced Nutrient
      Supply.
AB  - BACKGROUND: Optimal nutrient supply to very low birth weight (VLBW: BW <1,500 g)
      infants is important for growth and neurodevelopment. Growth restriction is
      common among these infants and may be associated with neurocognitive impairments.
      OBJECTIVES: To compare an enhanced nutrient supply to a routine supply given to
      VLBW infants and to evaluate the effects on visual perception of global form and
      motion measured by visual event-related potentials (VERP). METHODS: A total of 50
      VLBW infants were randomized to an intervention group that received an increased
      supply of energy, protein, fat, essential fatty acids, and vitamin A or a control
      group that received standard nutritional care. At 5 months' corrected age the
      infants were examined using VERP to investigate the responses to global form and
      motion. VERP were analysed at the first (f1) and third (f3) harmonics of the
      stimulus frequency. RESULTS: Data from 31 subjects were eligible for analysis.
      The motion VERP responses for the f1 and f3 components were stronger in the area
      near the posterior midline region in the intervention group compared to the
      controls in the group analyses (p = 0.02 and p = 0.001, respectively).
      CONCLUSION: The results showed a more consistent response to global motion among
      infants receiving enhanced nutrition. The intervention may have improved visual
      perception of global motion.

PMID- 25967895
TI  - Practice versus training in pulmonology.

PMID- 25967894
TI  - Severe/mild haemoptyses - Pulmonologist intervention.

PMID- 25967896
TI  - About the XXIV Congress of Pulmonology.

PMID- 25967897
TI  - Different Slopes for Different Folks: Genetic Influences on Growth in Delinquent
      Peer Association and Delinquency During Adolescence.
AB  - An extensive line of research has identified delinquent peer association as a
      salient environmental risk factor for delinquency, especially during adolescence.
      While previous research has found moderate-to-strong associations between
      exposure to delinquent peers and a variety of delinquent behaviors, comparatively
      less scholarship has focused on the genetic architecture of this association over
      the course of adolescence. Using a subsample of kinship pairs (N = 2379; 52%
      female) from the National Longitudinal Survey of Youth-Child and Young Adult
      Supplement (CNLSY), the present study examined the extent to which correlated
      individual differences in starting levels and developmental growth in delinquent
      peer pressure and self-reported delinquency were explained by additive genetic
      and environmental influences. Results from a series of biometric growth models
      revealed that 37% of the variance in correlated growth between delinquent peer
      pressure and self-reported delinquency was explained by additive genetic effects,
      while nonshared environmental effects accounted for the remaining 63% of the
      variance. Implications of these findings for interpreting the nexus between peer
      effects and adolescent delinquency are discussed.

PMID- 25967899
TI  - Guiding our PCR experiments.

PMID- 25967898
TI  - Cholinergic neurons intrinsic to the primate external pallidum.
AB  - We report the presence of a small population of cholinergic neurons closely
      intermingled with external pallidal neurons in cynomolgus monkeys (Macaca
      fascicularis). The majority of these cholinergic pallidal neurons are devoid of
      Nerve Growth Factor receptor (NGFr), which sets them apart from the population of
      corticopetal NGFr-rich neurons of the nucleus basalis of Meynert and its ectopic
      elements that impinge dorsally upon the pallidum via the medullary laminae.

PMID- 25967900
TI  - CRISPR/Cas faces the bioethics spotlight.

PMID- 25967901
TI  - In vitro use of free fatty acids bound to albumin: A comparison of protocols.

PMID- 25967902
TI  - Non-destructive high-throughput DNA extraction and genotyping methods for cotton
      seeds and seedlings.
AB  - Extensive use of targeted PCR-based genotyping is precluded for many plant
      research laboratories by the cost and time required for DNA extraction. Using
      cotton (Gossypium hirsutum) as a model for plants with medium-sized seeds, we
      report here manual procedures for inexpensive non-destructive high-throughput
      extraction of DNA suitable for PCR-based genotyping of large numbers of
      individual seeds and seedlings. By sampling only small amounts of cotyledon
      tissue of ungerminated seed or young seedlings, damage is minimized, and
      viability is not discernibly affected. The yield of DNA from each seed or
      seedling is typically sufficient for 1000 or 500 PCR reactions, respectively. For
      seeds, the tissue sampling procedure relies on a modified 96-well plate that is
      used subsequently for seed storage. For seeds and seedlings, the DNA is extracted
      in a strongly basic DNA buffer that is later neutralized and diluted. Extracts
      can be used directly for high-throughput PCR-based genotyping. Any laboratory can
      thus extract DNA from thousands of individual seeds/seedlings per person-day at a
      very modest cost for consumables (~$0.05 per sample). Being non-destructive, our
      approach enables a wide variety of time- and resource-saving applications, such
      as marker-assisted selection (MAS), before planting, transplanting, and
      flowering. 

PMID- 25967903
TI  - Rapid quantification of microRNAs in plasma using a fast real-time PCR system.
AB  - The ability to rapidly detect circulating small RNAs, in particular microRNAs
      (miRNAs), would further increase their already established potential as
      biomarkers for a range of conditions. One rate-limiting factor in miRNA detection
      is the time taken to perform quantitative real-time PCR (qPCR) amplification. We
      therefore evaluated the ability of a novel thermal cycler to perform this step in
      less than 10 minutes. Quantitative PCR was performed on an xxpress thermal cycler
      (BJS Biotechnologies), which employs a resistive heating system and forced air
      cooling to achieve thermal ramp rates of 10 degrees C/s, and a conventional
      Peltier-controlled LightCycler 480 system (Roche) ramping at 4.8 degrees C/s. The
      quantification cycle (Cq) for detection of 18S rDNA from a standard genomic DNA
      sample was significantly more variable across the block (F-test, P = 2.4 * 10(
      25)) for the xxpress (20.01 +/- 0.47 sd) than for the LightCycler (19.87 +/- 0.04
      sd). RNA was extracted from human plasma, reverse transcribed, and a panel of
      miRNAs was amplified and detected using SYBR Green. The sensitivities of the two
      systems were broadly comparable-both detected a panel of miRNAs reliably, and
      both indicated similar relative abundances. The xxpress thermal cycler
      facilitates rapid qPCR detection of small RNAs and brings point-of-care
      diagnostics based upon detection of circulating miRNAs a step closer to reality. 

PMID- 25967904
TI  - Optimization and cost-saving in tagmentation-based mate-pair library preparation
      and sequencing.
AB  - In de novo genome sequencing, mate-pair reads are crucial for scaffolding
      assembled contigs. However, preparation of mate-pair libraries is not a trivial
      task, even when using one of the latest approaches, the Nextera Mate Pair Sample
      Prep Kit from Illumina. To reduce cost and enhance library yield and fidelity
      when using this kit, we have modified the manufacturer's protocol based on (i)
      variable tagmentation conditions, (ii) intensive DNA shearing to decrease library
      insert length, and (iii) sequencing on an Illumina HiSeq with >150 cycles.
      Finally, we provide additional suggestions for further improvement in the
      application of this kit. 

PMID- 25967905
TI  - Influence of cell growth conditions and medium composition on EGFP photostability
      in live cells.
AB  - Photostability is a key characteristic of fluorescent proteins. It was recently
      demonstrated that green fluorescent protein (GFP) photobleaching in live cells
      can be suppressed by changes in medium composition. Here we show that Ham's F12
      medium provides very high enhanced GFP (EGFP) photostability during fluorescence
      microscopy of live cells. This property of Ham's F12 medium is associated with
      decreased concentrations of riboflavin and pyridoxine, and increased
      concentrations of FeSO4, cyanocobalamine, lipoic acid, hypoxanthine, and
      thymidine compared with DMEM. We also found that the rate of EGFP photobleaching
      strongly depends on cell growth conditions such as cell density and the
      concentration of serum. We conclude that both imaging medium composition and the
      physiological state of the cells can strongly affect the photostability of
      fluorescent proteins. Thus, accurate comparison of the photostabilities of
      fluorescent proteins should be performed only in side-by-side analysis in
      identical cell growth conditions and media. 

PMID- 25967906
TI  - A simple modification to the luminometric methylation assay to control for the
      effects of DNA fragmentation.
AB  - Variations in DNA methylation have been implicated in a number of disorders.
      Changes in global DNA methylation levels have long been associated with various
      types of cancer. One of the recently described methods for determining global DNA
      methylation levels is the LUminometric Methylation Assay (LUMA), which utilizes
      methylation sensitive and insensitive restriction endonucleases and
      pyrosequencing technology for quantification. Here we provide evidence suggesting
      that the global methylation level reported by LUMA is affected by the integrity
      of the DNA being analyzed. The less intact the DNA, the lower the global
      methylation levels reported by LUMA. In order to overcome this problem, we
      propose the use of undigested DNA alongside digested samples. Finally, we
      demonstrate that this results in a more accurate assessment of global DNA
      methylation levels. 

PMID- 25967907
TI  - Choosing Treatments on the Basis of Cost: Can Clinicians Opt for Less Expensive
      Treatments?

PMID- 25967910
TI  - Innovative taught MSc in Medical Visualisation and Human Anatomy.
AB  - A relatively new, fully accredited MSc in Medical Visualisation and Human
      Anatomy, is now offered through a joint collaboration with the Laboratory of
      Human Anatomy, University of Glasgow and the Digital Design Studio, Glasgow
      School of Art. This degree combines training in digital technologies and
      intensive human anatomy training as a result of a long-standing successful
      partnership between these two esteemed institutes. The student also has to
      complete a research dissertation which encompasses both the digital perspective
      and a related medical, dental, surgical, veterinary (comparative anatomy) or life
      science specialty to enhance development in the digital field for a variety of
      specialties. This article discusses the background in development of this degree,
      the course structure and the career prospects and destinations for graduates of
      this unique degree programme. 

PMID- 25967912
TI  - Combined Hamartoma (CHR-RPE). A Case Study.

PMID- 25967914
TI  - MSc's in Medical and Forensic Art and Facial Identification. A reflection on the
      last seven years, highlighting good practice, challenges and future changes.
AB  - The MSc's in Medical and Forensic Art have been running at the University Dundee
      for over seven years. Many changes have taken place since the first intake in
      September 2007. This paper will examine how the course has developed over this
      time, reflecting on examples of good practice, including innovative teaching
      methods and assessment practices. It will discuss how challenges have been
      overcome and explore the changes planned for September 2015. 

PMID- 25967915
TI  - Careers and Emerging Opportunities in Visual Communication in Medicine: Medical
      photography in Norway.
AB  - The community of medical photographers in Norway is relatively small. Except for
      one they are all employed with titles such as research technicians, department
      engineers, senior consultants and skilled workers. At the present there is no
      formal education in medical photography. The most common educational attainment
      for photographers is the Journeyman's certificate. Until recently, the
      requirement for employment for photographers at Norwegian hospitals was the
      Journeyman's Certificate. However, the Institutt for Klinisk Medisin at
      University in Oslo recently advertised a vacancy for a departmental Engineer to
      run its photographic and video services. The post required that the candidates
      possess either a Bachelor's degree in a relevant subject. This is the first
      vacancy in medical photography in nine years. The Norwegian health services have
      been reformed in the direction of New Public Management (NPM). To utilise the
      resources effectively, tasks that normally would be performed by one health
      profession are shifted to another with a different or lower education and
      training. There are reasons to believe that the shift of medical photography from
      professional photographers to other health personnel without specialist training
      or qualifications is an attempt to utilise resources more effectively. During the
      next two years a mixed methods research will be carried out to explore the
      current situation for medical photography in Norway. 

PMID- 25967919
TI  - How we treat delayed haemolytic transfusion reactions in patients with sickle
      cell disease.
AB  - Transfusion therapy is effective in the prevention and treatment of many
      complications of sickle cell disease (SCD). However, its benefits must be
      balanced against its risks, including delayed haemolytic transfusion reactions
      (DHTR). Not only is the relative rate of alloimmunization higher in patients with
      SCD than in other patient populations, but attendant risks associated with DHTR
      are even greater in SCD. Clinicians' awareness of DHTR events is poor because
      symptoms of DHTR mimic acute vaso-occlusive pain and immunohaematology findings
      are often negative. Transfusions delivered in the acute rather than elective
      setting appear to confer a higher risk of DHTR. Management of DHTR in SCD depends
      on the clinical severity, ranging from supportive care to immunosuppression, and
      optimization of erythropoiesis. DHTR must be considered in any recently
      transfused patient presenting with acute sickle cell pain. Meticulous
      documentation of transfusion and immunohaematology history is key. We anticipate
      an increase in DHTR events in SCD patients with the increasing use of red blood
      cell transfusion therapy. 

PMID- 25967920
TI  - Mediating role of television time, diet patterns, physical activity and sleep
      duration in the association between television in the bedroom and adiposity in 10
      year-old children.
AB  - BACKGROUND: Having a TV in the bedroom is associated with adiposity in children.
      It is not known how lifestyle behaviours (television viewing time, diet patterns,
      physical activity, and sleep duration) mediate this association. The objective of
      this study was to examine the mediating role of these lifestyle behaviours in the
      association between TV in the bedroom and percent body fat (% BF). METHODS: Cross
      sectional data from 1 201 children (57.3% female; mean age = 9.8 years) from
      Ottawa, Canada and Baton Rouge, USA were examined. % BF was directly measured.
      Accelerometers were used to determine physical activity and sleep duration (24-h,
      7-day protocol). Questionnaires were used to assess TV viewing time and
      healthy/unhealthy diet patterns (derived using factor analysis from food
      frequency questionnaire data). RESULTS: Canadian boys and girls with a TV in
      their bedroom had a higher % BF, watched more TV and had unhealthier diets.
      American boys and girls with a TV in their bedroom watched more TV, while boys
      had a higher % BF and a more unhealthy diet, and girls had less MVPA. In Canadian
      girls, TV viewing time mediated the association between having a TV in the
      bedroom and adiposity, independent of diet patterns, MVPA, and sleep duration.
      Other lifestyle mediators were not significant in Canadian boys or in US
      children. CONCLUSION: TV viewing is a mediating lifestyle behaviour in the
      association between TV in the bedroom and adiposity in Canadian girls. Future
      research is needed to identify lifestyle behaviours as intermediate mediators.

PMID- 25967921
TI  - Can graphene quantum dots cause DNA damage in cells?
AB  - Graphene quantum dots (GQDs) have attracted tremendous attention for biological
      applications. We report the first study on cytotoxicity and genotoxicity of GQDs
      to fibroblast cell lines (NIH-3T3 cells). The NIH-3T3 cells treated with GQDs at
      dosages over 50 MUg mL(-1) showed no significant cytotoxicity. However, the GQD
      treated NIH-3T3 cells exhibited an increased expression of proteins (p53, Rad 51,
      and OGG1) related to DNA damage compared with untreated cells, indicating the DNA
      damage caused by GQDs. The GQD-induced release of reactive oxygen species (ROS)
      was demonstrated to be responsible for the observed DNA damage. These findings
      should have important implications for future applications of GQDs in biological
      systems. 

PMID- 25967922
TI  - MRI Surface-Based Brain Morphometry in Egyptian Autistic and Typically Developing
      Children.
AB  - OBJECTIVES: The verbal abilities of autistic children differ from those of
      typically developing ones and they also differ among autistic children
      themselves. Neuroanatomical changes and an abnormal organization of functional
      networks are expected to accompany such a neurodevelopmental disorder. The aim of
      this study was to delineate the brain neuroanatomical changes in Egyptian
      children with autism and to compare them with previous studies in order to add
      more insight into the global brain imaging deviations linked to autism. PATIENTS
      AND METHODS: Twenty-five autistic children and 25 typically developing children
      underwent MRI. Further analysis was performed using surface-based morphometry to
      obtain cortical thickness, brain volume, and cortical complexity. RESULTS: MRI
      analysis results revealed significantly greater cortical thickness, cortical
      complexity, and gray matter volume in the autistic as compared to the control
      group. On the other hand, the white matter volume was significantly smaller.
      CONCLUSION: These findings generally align with findings in previous studies,
      except for occasional differences.

PMID- 25967923
TI  - Early postnatal respiratory viral infection induces structural and neurochemical
      changes in the neonatal piglet brain.
AB  - Infections that cause inflammation during the postnatal period are common, yet
      little is known about their impact on brain development in gyrencephalic species.
      To address this issue, we investigated brain development in domestic piglets
      which have brain growth and morphology similar to human infants, after
      experimentally infecting them with porcine reproductive and respiratory syndrome
      virus (PRRSV) to induce an interstitial pneumonia Piglets were inoculated with
      PRRSV on postnatal day (PD) 7 and magnetic resonance imaging (MRI) was used to
      assess brain macrostructure (voxel-based morphometry), microstructure (diffusion
      tensor imaging) and neurochemistry (MR-spectroscopy) at PD 29 or 30. PRRSV
      piglets exhibited signs of infection throughout the post-inoculation period and
      had elevated plasma levels of TNFalpha at the end of the study. PRRSV infection
      increased the volume of several components of the ventricular system including
      the cerebral aqueduct, fourth ventricle, and the lateral ventricles. Group
      comparisons between control and PRRSV piglets defined 8 areas where PRRSV piglets
      had less gray matter volume; 5 areas where PRRSV piglets had less white matter
      volume; and 4 relatively small areas where PRRSV piglets had more white matter.
      Of particular interest was a bilateral reduction in gray and white matter in the
      primary visual cortex. PRRSV piglets tended to have reduced fractional anisotropy
      in the corpus callosum. Additionally, N-acetylaspartate, creatine, and myo
      inositol were decreased in the hippocampus of PRRSV piglets suggesting disrupted
      neuronal and glial health and energy imbalances. These findings show in a
      gyrencephalic species that early-life infection can affect brain growth and
      development. 

PMID- 25967924
TI  - Laxatives for the management of constipation in people receiving palliative care.
AB  - BACKGROUND: This article describes the second update of a Cochrane review on the
      effectiveness of laxatives for the management of constipation in people receiving
      palliative care. Previous versions were published in 2006 and 2010 where we also
      evaluated trials of methylnaltrexone; these trials have been removed as they are
      included in another review in press. In these earlier versions, we drew no
      conclusions on individual effectiveness of different laxatives because of the
      limited number of evaluations. This is despite constipation being common in
      palliative care, generating considerable suffering due to the unpleasant physical
      symptoms and the availability of a wide range of laxatives with known differences
      in effect in other populations. OBJECTIVES: To determine the effectiveness and
      differential efficacy of laxatives used to manage constipation in people
      receiving palliative care. SEARCH METHODS: We searched the Cochrane Central
      Register of Controlled Trials (CENTRAL; The Cochrane Library), MEDLINE, EMBASE,
      CINAHL and Web of Science (SCI & CPCI-S) for trials to September 2014. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) evaluating laxatives for
      constipation in people receiving palliative care. DATA COLLECTION AND ANALYSIS:
      Two authors assessed trial quality and extracted data. The appropriateness of
      combining data from the studies depended upon clinical and outcome measure
      homogeneity. MAIN RESULTS: We identified five studies involving the laxatives
      lactulose, senna, co-danthramer, misrakasneham, docusate and magnesium hydroxide
      with liquid paraffin. Overall, the study findings were at an unclear risk of
      bias. As all five studies compared different laxatives or combinations of
      laxatives, it was not possible to perform a meta-analysis. There was no evidence
      on whether individual laxatives were more effective than others or caused fewer
      adverse effects. AUTHORS' CONCLUSIONS: This second update found that laxatives
      were of similar effectiveness but the evidence remains limited due to
      insufficient data from a few small RCTs. None of the studies evaluated
      polyethylene glycol or any intervention given rectally. There is a need for more
      trials to evaluate the effectiveness of laxatives in palliative care populations.
      Extrapolating findings on the effectiveness of laxatives evaluated in other
      populations should proceed with caution. This is because of the differences
      inherent in people receiving palliative care that may impact, in a likely
      negative way, on the effect of a laxative.

PMID- 25967926
TI  - 2-(2'-Pyridyl)-4,6-diphenylphosphinine versus 2-(2'-pyridyl)-4,6
      diphenylpyridine: synthesis and characterization of novel Cr(0), Mo(0) and W(0)
      carbonyl complexes containing chelating P,N and N,N ligands.
AB  - Replacing nitrogen by phosphorus in otherwise similar structures changes the
      properties of the resulting compounds significantly due to the electronic
      differences that exist between these heteroatoms. While the "hard" nitrogen atom
      of the pyridine moiety acts as a good sigma-donor, the "soft" phosphorus atom of
      the phosphinine core results in a rather strong pi-acceptor capacity. A series of
      novel group 6 complexes [M(CO)4(L^L)] (M = Cr(0), Mo(0), W(0)) have been
      synthesized, in which L^L is either 2-(2'-pyridyl)-4,6-diphenylphosphinine (P,N)
      or the corresponding bipyridine derivative, 2-(2'-pyridyl)-4,6-diphenylpyridine
      (N,N) as a chelating, bidentate ligand. The here presented results describe a
      detailed investigation of the structural and spectroscopic properties of the
      coordination compounds [M(CO)4(P,N)] and [M(CO)4(N,N)] (M = Cr(0), Mo(0), W(0)),
      leading to a better understanding of such intriguing aromatic phosphorus
      heterocycles. 

PMID- 25967925
TI  - Clinical Immunogenicity of rHuPH20, a Hyaluronidase Enabling Subcutaneous Drug
      Administration.
AB  - Recombinant human PH20 hyaluronidase (rHuPH20) is used to facilitate dispersion
      of subcutaneously delivered fluids and drugs. This report summarizes rHuPH20
      immunogenicity findings from clinical trials where rHuPH20 was co-administered
      with SC human immunoglobulin, trastuzumab, rituximab, or insulin. Plasma samples
      were obtained from evaluable subjects participating in ten different clinical
      trials as well as from healthy plasma donors. A bridging immunoassay and a
      modified hyaluronidase activity assay were used to determine rHuPH20-reactive
      antibody titers and neutralizing antibodies, respectively. rHuPH20-binding
      antibody populations from selected subjects with positive titers were affinity
      purified and subjected to further characterization such as cross-reactivity with
      endogenous PH20. Among individual trials, the prevalence of pre-existing rHuPH20
      reactive antibodies varied between 3 and 12%, excepting the primary
      immunodeficiency (PID) studies. Incidence of treatment-induced rHuPH20 antibodies
      was 2 to 18%, with the highest titers (81,920) observed in PID. No neutralizing
      antibodies were observed. Within most trials, the kinetics of antibody responses
      were comparable between pre-existing and treatment-induced antibody responses,
      although responses classified as persistent were more common in subjects with pre
      existing titers. There was no association between antibody positivity and either
      local or systemic adverse events. Pre-existing and treatment-induced antibody
      populations were of similar immunoglobulin isotypes and cross-reacted to
      endogenous PH20 to similar extents. No cross-reactivity to PH20 paralogs was
      detected. rHuPH20 induces only modest immunogenicity which has no association
      with adverse events. In addition, antibodies purified from baseline-positive
      individuals are qualitatively similar to those purified from individuals
      developing rHuPH20-reactive antibodies following exposure to the enzyme. 

PMID- 25967927
TI  - Evaluating fluctuating asymmetry in a Brazilian population with non-syndromic
      cleft lip and/or palate.
AB  - OBJECTIVE: The objective of this work was to analyse the levels of dermatoglyphic
      asymmetry between both parents and individuals with non-syndromic cleft lip
      and/or palate (NSCL/P) and unaffected control trios. METHODS: A case-control
      analysis was carried out of 51 affected trios (unaffected parents and NSCL/P
      subjects), and 50 unaffected control trios. Finger and palm prints were taken
      from each participant, and dermatoglyphic patterns, the number of lines on the
      digits, and the palmar angles were recorded. To determine the level of
      fluctuating asymmetry the case group was compared with the control group,
      significance accepted at p <= 0.05. RESULTS: There was a statistically
      significant difference between the atd angles (angle between the lines triradii a
      and t and triradii t and d) of fathers of those affected by NSCL/P, and the
      dermatoglyphic patterns of the affected mothers, with significantly more arches
      in the control group. However, in this study, multiple comparisons were used, and
      the results must be evaluated as initial findings and evaluated carefully since
      the significance disappears after correction for multiple comparisons. Other
      parameters did not differ between groups. There was no difference in parameters
      among patients affected by NSCL/P. CONCLUSIONS: Based on these results it is
      speculated that the mechanisms responsible for the formation of NSCL/P may be
      associated with those responsible for deviations in the asymmetry of the atd
      angles in the fathers and dermatoglyphic patterns of the mothers of affected
      patients. Besides, further studies are required to determine the real
      relationship between these conditions.

PMID- 25967928
TI  - Cobalt(II)/silver relay catalytic isocyanide insertion/cycloaddition cascades: a
      new access to pyrrolo[2,3-b]indoles.
AB  - The combination of Co(acac)2 and AgOTf enables the bimetallic relay catalysis
      reaction of 2-ethynylanilines and isocyanides, allowing easy and low-cost access
      to new densely functionalized pyrrolo[2,3-b]indoles. The reaction pathway
      involves a Co(acac)2-catalyzed double isocyanide insertion followed by a silver
      enabled 1,3-dipolar cycloaddition. The synthetic utility of these bicycloaddition
      reactions results in subsequent C-C and C-N bond-forming events to rapidly build
      up molecular complexity. 

PMID- 25967930
TI  - This person is saying bad things about you: The influence of physically and
      socially threatening context information on the processing of inherently neutral
      faces.
AB  - Recent studies have shown that the perceptual processing of human faces is
      affected by context information, such as previous experiences and information
      about the person represented by the face. The present study investigated the
      impact of verbally presented information about the person that varied with
      respect to affect (neutral, physically threatening, socially threatening) and
      reference (self-referred, other-referred) on the processing of faces with an
      inherently neutral expression. Stimuli were presented in a randomized
      presentation paradigm. Event-related potential (ERP) analysis demonstrated a
      modulation of the evoked potentials by reference at the EPN (early posterior
      negativity) and LPP (late positive potential) stage and an enhancing effect of
      affective valence on the LPP (700-1000 ms) with socially threatening context
      information leading to the most pronounced LPP amplitudes. We also found an
      interaction between reference and valence with self-related neutral context
      information leading to more pronounced LPP than other related neutral context
      information. Our results indicate an impact of self-reference on early,
      presumably automatic processing stages and also a strong impact of valence on
      later stages. Using a randomized presentation paradigm, this study confirms that
      context information affects the visual processing of faces, ruling out possible
      confounding factors such as facial configuration or conditional learning effects.

PMID- 25967931
TI  - Impact of acute kidney injury on prognosis of patients with liver cirrhosis and
      ascites: A retrospective cohort study.
AB  - BACKGROUND AND AIM: Acute kidney injury (AKI) is a common complication in
      patients with liver cirrhosis, and its impact on the clinical course is
      increasingly recognized. Diagnostic classification systems for AKI in cirrhosis
      have been suggested. The prognostic significance of the respective AKI stages
      remains to be evaluated in decompensated cirrhosis with ascites. METHODS: Data of
      consecutive patients with cirrhosis and ascites undergoing paracentesis at a
      tertiary care center were analyzed. AKI was defined as an increase in serum
      creatinine of >= 0.3 mg/dL or by >= 50% within 7 days after paracentesis, and
      classified according to (i) revised Acute Kidney Injury Network (AKIN) criteria
      and (ii) modified AKI criteria for cirrhosis (C-AKI). In contrast to AKIN, C-AKI
      stage A discriminates prognosis based on an absolute creatinine cut-off at < 1.5
      mg/dL versus C-AKI stage B at >= 1.5 mg/dL. RESULTS: The final study cohort
      included 239 patients. Median transplant-free survival was 768 days (95%
      confidence interval [CI]: 331-1205 days) without AKI, 198 (0-446) in AKI-1, 91 (0
      225) in AKI-2, 19 (0-40) and in AKI-3, whereas it was 89 (20-158) days in C-AKI
      A, 384 (0-1063) in C-AKI-B, and 22 (7-776) in C-AKI-C. Mild AKI was already
      associated with significantly increased 30-day mortality (AKI-1:26.4%, C-AKI
      A:33.3%) as compared with patients without AKI (14.3%), even when serum
      creatinine remained within normal range (< 1.2 mg/dL) we observed a significant
      30-day mortality. CONCLUSION: AKIN criteria-considering small increases in serum
      creatinine rather than absolute thresholds-seem to be more accurate for
      estimating prognosis of AKI after paracentesis than C-AKI criteria. Even patients
      developing AKI-1 with "normal" serum creatinine are at increased risk for
      mortality.

PMID- 25967932
TI  - Brentuximab vedotin for the treatment of Hodgkin's lymphoma.
AB  - Although Hodgkin's lymphoma is considered a highly curable cancer, a substantial
      portion of patients will be refractory or will relapse after first-line therapies
      and even after subsequent autologous stem cell transplantation. With the absence
      of effective salvage therapies, these patients carry a poor prognosis with dismal
      survival. In this therapeutic void, the antibody-drug conjugate brentuximab
      vedotin was introduced and has since yielded impressive and durable response with
      minimal and reversible toxicity. Such efficacy in the relapse-refractory setting
      has led to new hypotheses and dramatic changes in our treatment strategies of
      Hodgkin's lymphoma. Numerous clinical trials evaluating brentuximab in the
      frontline and various other treatment settings are forthcoming and will
      demonstrate the full extent of the drug's impact. 

PMID- 25967929
TI  - Individual differences in social anxiety affect the salience of errors in social
      contexts.
AB  - The error-related negativity (ERN) is an event-related potential that occurs
      approximately 50 ms after an erroneous response. The magnitude of the ERN is
      influenced by contextual factors, such as when errors are made during social
      evaluation. The ERN is also influenced by individual differences in anxiety, and
      it is elevated among anxious individuals. However, little research has examined
      how individual differences in anxiety interact with contextual factors to impact
      the ERN. Social anxiety involves fear and apprehension of social evaluation. In
      the present study, we explored how individual differences in social anxiety
      interact with social contexts to modulate the ERN. The ERN was measured in 43
      young adults characterized as being either high or low in social anxiety, while
      they completed a flanker task in two contexts: alone and during social
      evaluation. The results revealed a significant interaction between social anxiety
      and context, such that the ERN was enhanced in a social relative to a nonsocial
      context only among highly socially anxious individuals. Furthermore, the degree
      of such enhancement significantly correlated with individual differences in
      social anxiety. These findings demonstrate that social anxiety is characterized
      by enhanced neural activity to errors in social-evaluative contexts.

PMID- 25967933
TI  - Laparoscopic Sentinel Node Biopsy Using Real-time 3-dimensional Single-photon
      Emission Computed Tomographic Guidance in Endometrial Cancer.
AB  - In endometrial cancer, the histopathological analysis of the lymphatic nodes is
      essential to establish a correct prognosis and tailored adjuvant treatment. It is
      well-known that patients with early-stage endometrial cancer have a low incidence
      of nodal disease. In this group, systematic lymphadenectomy is not recommended.
      To improve the detection rate of sentinel nodes in clinical practice, new
      techniques are emerging like real-time 3-dimensional single-photon emission
      computed tomographic (SPECT) imaging. We report our experience using this
      innovative technique for intraoperative detection of sentinel nodes in
      endometrial cancer. The real-time 3-dimensional SPECT sentinel node biopsy seems
      to be feasible and accurate in endometrial cancer although further studies are
      needed to set the precision and predictive values compared with the current
      differed SPECT techniques and blue dye techniques. 

PMID- 25967934
TI  - Postoperative Pain Scores and Narcotic Use in Robotic-assisted Versus
      Laparoscopic Hysterectomy for Endometrial Cancer Staging.
AB  - STUDY OBJECTIVE: To retrospectively evaluate perioperative pain and analgesic and
      antiemetic use in patients who underwent surgical staging for endometrial cancer
      using traditional versus robotic-assisted laparoscopy. DESIGN: We identified
      women in a single institution who underwent minimally hysterectomy for
      endometrial cancer from 2008 to 2012. Patient characteristics and perioperative
      outcomes, including analgesic and antiemetic use and pain scores, were analyzed.
      After univariate analysis, a multivariate linear regression model was generated
      to determine factors associated with narcotic use in the post anesthesia care
      unit (PACU) (Canadian Task Force Classification II-3). SETTING: A single academic
      institution in the United States from 2008 to 2012. PATIENTS: Women undergoing
      total laparoscopic hysterectomy or robotic-assisted laparoscopic hysterectomy for
      endometrial cancer. INTERVENTIONS: Laparoscopic or robotic-assisted laparoscopic
      hysterectomy. MEASUREMENTS AND MAIN RESULTS: Three hundred thirty-five women were
      included (213 laparoscopy and 122 robotic-assisted laparoscopy). There was no
      difference in pain scores at 0 to 6 and 6 to 12 hours after surgery; at 12 to 24
      hours, robotic-assisted surgery was associated with higher median pain scores
      (5/10 vs 4/10, p = .012). Robotic-assisted surgery was associated with a longer
      anesthesia time (289 vs 255 minutes, p < .001), similar antiemetic use (p = .40),
      and lower narcotic use in the postanesthesia care unit (PACU) (1.3 mg vs 2.5 mg
      morphine equivalents, p = .003). There was no difference in narcotic use on the
      postoperative floor (p = .46). In multivariate analysis controlling for age,
      menopausal status, anesthesia duration, and local anesthetic use, hysterectomy
      type was not a significant predictor of PACU narcotic use (p = .86). CONCLUSIONS:
      In a retrospective analysis, a robotic-assisted approach to endometrial cancer
      was not associated with reduced PACU narcotic or antiemetic use compared with the
      traditional laparoscopic approach. Twenty-four-hour narcotic and antiemetic use
      was also not different between the 2 approaches.

PMID- 25967935
TI  - Myocarditis or "true" infarction by cardiac magnetic resonance in patients with a
      clinical diagnosis of myocardial infarction without obstructive coronary disease:
      A meta-analysis of individual patient data.
AB  - OBJECTIVE: Myocardial Infarction with Non-Obstructed Coronary Arteries (MINOCA)
      is common, but the causes are to a large extent unknown. Thus, we aimed to study
      the prevalence of myocarditis and "true" myocardial infarction determined by
      cardiac magnetic resonance (CMR) imaging in MINOCA patients, and risk markers for
      these two conditions in this population. METHODS: A search was made in the PubMed
      and Cochrane databases using the search terms "Myocardial infarction", "Coronary
      angiography", "Normal coronary arteries" and "MRI". All relevant abstracts were
      read and seven of the studies fulfilled the inclusion criteria; studies
      describing case series of patients fulfilling the diagnosis of acute myocardial
      infarction with normal or non-obstructive coronary arteries on coronary
      angiography that were investigated with CMR imaging. Data from five of these
      studies are presented. RESULTS: A total of 556 patients from 5 different sites
      were included. Fifty-one percent were men with a mean age of 52 +/- 16 years.
      Thirty-three per cent of the patients had myocarditis (n = 183), whereas 21% of
      the patients had infarction on CMR (n = 115). Young age and a high CRP were
      associated with myocarditis whereas male sex, treated hyperlipidemia, high
      troponin ratio and low CRP were associated with "true" myocardial infarction.
      CONCLUSION AND RELEVANCE: The results of this meta-analysis of individual data
      showed that myocarditis and "true" myocardial infarction are common in MINOCA
      when determined by CMR imaging. This information emphasizes the importance of
      performing CMR imaging in MINOCA patients and can be used clinically to guide
      diagnostics and treatment of MINOCA patients.

PMID- 25967936
TI  - HIV Drug Therapy in the Americas 16-18 April 2015, Mexico City, Mexico.

PMID- 25967937
TI  - Planktonic community structure during a harmful bloom of Phaeocystis globosa in a
      subtropical bay, with special reference to the ciliate assemblages.
AB  - Planktonic community structure was investigated during outbreak of harmful
      Phaeocystis globosa bloom in a subtropical bay, the Maowei Sea, South China Sea.
      The phytoplankton assemblage was numerically dominated by colonial P. globosa,
      with its abundance ranging from 1.23 * 10(8) to 11.12 * 10(8) cells m(-3) and
      contributing nearly 90 % to the total abundance. Totally 66 mesozooplankton (>169
      um) and 19 ciliates species were recorded, with the densities ranged from 169 to
      1633 ind m(-3) and 74 to 1118 cells L(-1), respectively. The dominant species for
      mesozooplankton were Copepoda (larvae), Bestiola sinicus, B. amoyensis, Macrura
      (larvae) and Acartia spinicauda, respectively. The ciliate assemblage was
      numerically dominated by Codonella rapa, Strombidium globosaneum and Mesodinium
      rubrum. During the bloom, P. globosa seemed to be negatively affected by the
      nutrient phosphate significantly (p < 0.05). However, no correlation between P.
      globosa and ciliate assemblage was detected, but P. globosa was negatively
      correlated with total biomass of mesozooplankton and abundance of B. sinicus (p <
      0.05), suggesting that P. globosa was uncoupled from the grazing by both ciliates
      and mesozooplankton when appearing as colonies form. On the other hand, both
      positive and negative correlations among the dominant groups of mesozooplankton
      and ciliates were observed (p < 0.05) which possibly indicated that the predation
      of mesozooplankton upon ciliates might be strengthened during the Phaeocystis
      bloom and the complex effect also varied from species to species.

PMID- 25967938
TI  - Genetic population structure of polychaeta Neanthes glandicincta (Nereididae) of
      the Mai Po Inner Deep Bay Ramsar Site, Hong Kong.
AB  - Neanthes glandicincta (Nereididae, Polychaeta) is the first numerically dominant
      benthic infauna in the Mai Po international Ramsar site, Hong Kong and also an
      economically important species for food source of birds and fishes. In present
      study, highly conserved nuclear ribosomal DNA (SSU and LSU rDNA) and
      mitochondrial COI gene were employed to study the population structure of N.
      glandicincta in the subtropical mudflat. The specimens were collected from five
      localities in February 2006, February-August 2007 and preserved at -80  degrees
      C, methanol or formalin, respectively. DNA extraction efficiency was the highest
      in fresh materials and lowest in formalin-fixed samples. The 18S (1774 bp), 28S
      D1 (383 bp) and COI genes were sequenced and analyzed. Both 18S and 28S D1 rDNA
      were highly conserved and showed no difference among the populations, whereas COI
      gene exhibited relatively high-level intraspecific polymorphism (2.2 %). The
      population from onshore and near mangrove station was phylogenetic different from
      other sites, indicating restricted gene exchange between the region of river
      mouth and mangrove forest. The mangrove may form a barrier for the dispersal of
      pelagic/benthic larvae of the population, which indicates that the population
      genetic difference is related to different habitats.

PMID- 25967939
TI  - Isolated and combined exposure to ammonia and nitrite in giant freshwater pawn
      (Macrobrachium rosenbergii): effects on the oxidative stress, antioxidant
      enzymatic activities and apoptosis in haemocytes.
AB  - The residual contaminators such as ammonia and nitrite are widely considered as
      relevant sources of aquatic environmental pollutants, posing a great threat to
      shrimp survival. To study the toxicological effects of ammonia and nitrite
      exposure on the innate immune response in invertebrates, we investigated the
      oxidative stress and apoptosis in haemocytes of freshwater prawn (Macrobrachium
      rosenbergii) under isolated and combined exposure to ammonia and nitrite in order
      to provide useful information about adult prawn immune responses. M. rosenbergii
      (13.44 +/- 2.75 g) were exposed to 0, 5, and 25 mg/L total ammonia-N (TAN) and 0,
      5, and 20 mg/L nitrite-N for 24 h. All ammonia concentrations were combined with
      all nitrite concentrations, making a total of nine treatments studied. Following
      the exposure treatment, antioxidant enzyme activity, reactive oxygen species
      (ROS) generation, nitric oxide (NO) generation, and apoptotic cell ratio of
      haemocytes were measured using flow cytometry. Results indicated that ROS
      generation was sensitive to the combined effect of ammonia and nitrite, which
      subsequently affected the Cu-Zn SOD activity. In addition, CAT showed the highest
      activity at 5 mg/L TAN while GPx decreased at 5 mg/L TAN and returned towards
      baseline at 25 mg/L. NO generation synchronized with the apoptotic cell ratio in
      haemocytes, indicating that NO production was closely associated with programmed
      cell death. Both NO production and apoptotic ratios significantly decreased
      following 25 mg/L TAN, which may be due to the antagonistic regulation of NO and
      GPx. We hypothesized that the toxicological effect of nitrite exhibited less
      change in physiological changes compared to that of ammonia, because of the high
      tolerance to nitrite exposure in mature M. rosenbergii and/or the competitive
      effects of chloride ions. Taken together, these results showed that ammonia and
      nitrite caused a series of combined oxidative stress and apoptosis in M.
      rosenbergi, but further studies are of great need to explain the mechanisms.

PMID- 25967940
TI  - Assessment of the predictive accuracy of five in silico prediction tools, alone
      or in combination, and two metaservers to classify long QT syndrome gene
      mutations.
AB  - BACKGROUND: Long QT syndrome (LQTS) is an autosomal dominant condition
      predisposing to sudden death from malignant arrhythmia. Genetic testing
      identifies many missense single nucleotide variants of uncertain pathogenicity.
      Establishing genetic pathogenicity is an essential prerequisite to family cascade
      screening. Many laboratories use in silico prediction tools, either alone or in
      combination, or metaservers, in order to predict pathogenicity; however, their
      accuracy in the context of LQTS is unknown. We evaluated the accuracy of five in
      silico programs and two metaservers in the analysis of LQTS 1-3 gene variants.
      METHODS: The in silico tools SIFT, PolyPhen-2, PROVEAN, SNPs&GO and SNAP, either
      alone or in all possible combinations, and the metaservers Meta-SNP and
      PredictSNP, were tested on 312 KCNQ1, KCNH2 and SCN5A gene variants that have
      previously been characterised by either in vitro or co-segregation studies as
      either "pathogenic" (283) or "benign" (29). The accuracy, sensitivity,
      specificity and Matthews Correlation Coefficient (MCC) were calculated to
      determine the best combination of in silico tools for each LQTS gene, and when
      all genes are combined. RESULTS: The best combination of in silico tools for
      KCNQ1 is PROVEAN, SNPs&GO and SIFT (accuracy 92.7%, sensitivity 93.1%,
      specificity 100% and MCC 0.70). The best combination of in silico tools for KCNH2
      is SIFT and PROVEAN or PROVEAN, SNPs&GO and SIFT. Both combinations have the same
      scores for accuracy (91.1%), sensitivity (91.5%), specificity (87.5%) and MCC
      (0.62). In the case of SCN5A, SNAP and PROVEAN provided the best combination
      (accuracy 81.4%, sensitivity 86.9%, specificity 50.0%, and MCC 0.32). When all
      three LQT genes are combined, SIFT, PROVEAN and SNAP is the combination with the
      best performance (accuracy 82.7%, sensitivity 83.0%, specificity 80.0%, and MCC
      0.44). Both metaservers performed better than the single in silico tools;
      however, they did not perform better than the best performing combination of in
      silico tools. CONCLUSIONS: The combination of in silico tools with the best
      performance is gene-dependent. The in silico tools reported here may have some
      value in assessing variants in the KCNQ1 and KCNH2 genes, but caution should be
      taken when the analysis is applied to SCN5A gene variants.

PMID- 25967941
TI  - Tobacco documents reveal questionable professional recertification by industry
      menthol expert.

PMID- 25967942
TI  - Numerical investigation of thermo-magneto-solutal flow of ferrocolloid through
      ordered and disordered permeable membranes.
AB  - We explore the mechanism of ferroparticle transfer in porous structures in the
      conditions of simultaneous action of the thermal gradient and the magnetic field.
      We show that when a ferrocolloid saturated porous matrix is placed in a
      homogeneous magnetic field the grains of the porous frame notably distort the
      uniformity of the internal field by creating sharp gradients in the vicinity of
      the interface. On the other hand, the application of the temperature gradient
      creates an imbalance of the ferroparticle concentration in the bulk of the porous
      structure due to colloidal thermophoresis. The combination of the imbalance of
      concentration of the magnetic nanoparticles and the internal gradients of the
      magnetic field creates a magnetic force and convective flow of solution through
      the porous structure. We report the results of the pore-scale numerical
      simulations of the ferrocolloid thermo-magneto-solutal flow in geometrically
      simple ordered and disordered permeable structures and membranes with different
      porosity. 

PMID- 25967943
TI  - Dielectric alpha-relaxation of 1,4-polybutadiene confined between graphite walls
      : Molecular dynamics investigations through numerical simulations of polymer
      molecules relaxation.
AB  - We present results of Molecular Dynamics (MD) simulations of a chemically
      realistic model of 1,4-polybutadiene confined by crystalline graphite walls. The
      simulations cover a large range of temperatures from T ~ 2T g to T ~ 1.15T g,
      where relevant time scales are accessible using such computational methods. We
      investigate the dielectric relaxation close to the walls in comparison to the one
      in the center of the film, and study the latter as a function of the film
      thickness from the walls. The segmental dynamics in the film is slowed down close
      to the walls, in comparison to the bulk. In addition to the alpha-process, the
      relaxation exhibits an additional long time decay, the so-called wall desorption
      process. We focus here on the alpha-process and find no significant shift of the
      dielectric T g as a function of layer thickness, in agreement with recent
      dielectric experiments. These findings can be correlated with the importance of
      the dihedral dynamics for all relaxation processes in polymers, which is
      unaltered except for the first nanometer next to the walls. 

PMID- 25967944
TI  - [S3 guidelines on volume therapy: Comments on publication 2014].
AB  - Intravascular volume therapy represents one of the pillars of medical actions
      during inpatient treatment and is dealt with in the S3 guidelines on
      "intravascular volume therapy in adults". The target group of the guidelines are
      physicians who must carry out intravascular volume therapy as a component of
      patient treatment. This article critically reviews and summarizes the essential
      recommendations. 

PMID- 25967945
TI  - Predicting planned physical activity of individuals with arthritis: A self
      regulatory perspective.
AB  - Few individuals with arthritis are sufficiently active. We surveyed a convenience
      sample of exercisers ( N = 134) to examine the utility of social cognitive theory
      variables, namely, self-regulatory efficacy, negative outcome expectations, and
      pain acceptance for predicting planned physical activity according to Weinstein's
      two prediction suggestions. Logistic regression revealed, after controlling for
      pain intensity, self-regulatory efficacy, negative outcome expectations, and pain
      acceptance distinguished groups achieving/not achieving planned physical
      activity, p < 0.001 (28% variance). A second model adding past physical activity
      also predicted the groups, p < 0.001 (57% variance). This is one of the first
      arthritis studies examining planned physical activity relative to Weinstein's
      recommendations.

PMID- 25967946
TI  - An imaging flow cytometry-based approach to measuring the spatiotemporal calcium
      mobilisation in activated T cells.
AB  - Calcium ions (Ca(2+)) are a ubiquitous transducer of cellular signals controlling
      key processes such as proliferation, differentiation, secretion and metabolism.
      In the context of T cells, stimulation through the T cell receptor has been shown
      to induce the release of Ca(2+) from intracellular stores. This sudden elevation
      within the cytoplasm triggers the opening of ion channels in the plasma membrane
      allowing an influx of extracellular Ca(2+) that in turn activates key molecules
      such as calcineurin. This cascade ultimately results in gene transcription and
      changes in the cellular state. Traditional methods for measuring Ca(2+) include
      spectrophotometry, conventional flow cytometry (CFC) and live cell imaging
      techniques. While each method has strengths and weaknesses, none can offer a
      detailed picture of Ca(2+) mobilisation in response to various agonists. Here we
      report an Imaging Flow Cytometry (IFC)-based method that combines the throughput
      and statistical rigour of CFC with the spatial information of a microscope. By co
      staining cells with Ca(2+) indicators and organelle-specific dyes we can address
      the spatiotemporal patterns of Ca(2+) flux in Jurkat cells after stimulation with
      anti-CD3. The multispectral, high-throughput nature of IFC means that the
      organelle co-staining functions to direct the measurement of Ca(2+) indicator
      fluorescence to either the endoplasmic reticulum (ER) or the mitochondrial
      compartments without the need to treat cells with detergents such as digitonin to
      eliminate cytoplasmic background. We have used this system to look at the
      cellular localisation of Ca(2+) after stimulating cells with CD3, thapsigargin or
      ionomycin in the presence or absence of extracellular Ca(2+). Our data suggest
      that there is a dynamic interplay between the ER and mitochondrial compartments
      and that mitochondria act as a sink for both intracellular and extracellular
      derived Ca(2+). Moreover, by generating an NFAT-GFP expressing Jurkat line, we
      were able to combine mitochondrial Ca(2+) measurements with nuclear
      translocation. In conclusion, this method enables the high throughput study of
      spatiotemporal patterns of Ca2(+) signals in T cells responding to different
      stimuli. 

PMID- 25967947
TI  - An improved method for differentiating cell-bound from internalized particles by
      imaging flow cytometry.
AB  - Recognition, binding, internalization, and elimination of pathogens and cell
      debris are important functions of professional as well as non-professional
      phagocytes. However, high-throughput methods for quantifying cell-associated
      particles and discriminating bound from internalized particles have been lacking.
      Here we describe a protocol for using imaging flow cytometry to quantify the
      attached and phagocytosed particles that are associated with a population of
      cells. Cells were exposed to fluorescent particles, fixed, and exposed to an
      antibody of a different fluorophore that recognizes the particles. The antibody
      is added without cell permeabilization, such that the antibody only binds
      extracellular particles. Cells with and without associated particles were
      identified by imaging flow cytometry. For each cell with associated particles, a
      spot count algorithm was employed to quantify the number of extracellular (double
      fluorescent) and intracellular (single fluorescent) particles per cell, from
      which the percent particle internalization was determined. The spot count
      algorithm was empirically validated by examining the fluorescence and phase
      contrast images acquired by the flow cytometer. We used this protocol to measure
      binding and internalization of the bacterium Neisseria gonorrhoeae by primary
      human neutrophils, using different bacterial variants and under different
      cellular conditions. The results acquired using imaging flow cytometry agreed
      with findings that were previously obtained using conventional immunofluorescence
      microscopy. This protocol provides a rapid, powerful method for measuring the
      association and internalization of any particle by any cell type. 

PMID- 25967948
TI  - Imaging the immunological synapse between dendritic cells and T cells.
AB  - Immunological synapse formation between antigen-specific T cells and antigen
      presenting cells (APC) involves reorganization of the cellular cytoskeleton
      (polymerization of filamentous actin) and recruitment of adhesion molecules (e.g.
      LFA-1, ICAM-1). This engagement is critical for the generation of specific immune
      responses. Until recently, quantitative, high-throughput measurements of these
      interactions have not been possible. Instead, previous assessment was reliant on
      qualitative microscopy of live cells, where typically the APC is adhered to a
      surface and the suspended T cell is required to migrate to facilitate synapse
      formation. While this methodology can demonstrate the capacity for synapse
      formation, it cannot accommodate quantification of large numbers of interacting
      cell pairs, nor does it allow for statistically robust comparison between test
      conditions. We have developed a method for assessing immunological synapse
      formation between purified ex vivo dendritic cells (DCs) and responder antigen
      specific CD4(+) T cells using imaging flow cytometry, allowing us to quantify LFA
      1 and f-actin rearrangement at the interface between DC/T cell pairs. This novel
      application of imaging flow cytometry represents a major advance in dendritic
      cell function and immunological synapse research as it facilitates quantitative,
      high throughput analysis of the interaction between live, ex vivo DC and T cells.

PMID- 25967949
TI  - Quantification of CD95-induced apoptosis and NF-kappaB activation at the single
      cell level.
AB  - CD95/Fas/APO-1 is a member of the death receptor (DR) family. Stimulation of CD95
      leads to the induction of apoptosis as well as to NF-kappaB signaling. Crosstalk
      between these two pathways plays a central role in cell fate. Defects in the
      regulation of apoptosis and of NF-kappaB are connected to a number of chronic
      inflammatory diseases and cancer. For a better understanding of the life/death
      decisions in the cell and their contribution to disease progression, the
      development of new technologies is required. Using imaging flow cytometry we
      developed a method that enables a quantitative detection of different CD95
      signaling pathways in the single cell. The important advantage of this method
      compared to other approaches is that it allows quantifying a large number of
      single cells undergoing apoptosis and NF-kappaB activation. This technology could
      provide new insights into the quantitative characterization of apoptosis and NF
      kappaB at the single cell level and could be used for the quantitative network
      analysis in systems biology studies. 

PMID- 25967950
TI  - A novel method for measuring cellular antibody uptake using imaging flow
      cytometry reveals distinct uptake rates for two different monoclonal antibodies
      targeting L1.
AB  - Monoclonal antibodies (mAbs) have emerged as a promising tool for cancer therapy.
      Differing approaches utilize mAbs to either deliver a drug to the tumor cells or
      to modulate the host's immune system to mediate tumor kill. The rate by which a
      therapeutic antibody is being internalized by tumor cells is a decisive feature
      for choosing the appropriate treatment strategy. We herein present a novel method
      to effectively quantitate antibody uptake of tumor cells by using image-based
      flow cytometry, which combines image analysis with high throughput of sample
      numbers and sample size. The use of this method is established by determining
      uptake rate of an anti-EpCAM antibody (HEA125), from single cell measurements of
      plasma membrane versus internalized antibody, in conjunction with inhibitors of
      endocytosis. The method is then applied to two mAbs (L1-9.3, L1-OV52.24)
      targeting the neural cell adhesion molecule L1 (L1CAM) at two different epitopes.
      Based on median cell population responses, we find that mAb L1-OV52.24 is rapidly
      internalized by the ovarian carcinoma cell line SKOV3ip while L1 mAb 9.3 is
      mainly retained at the cell surface. These findings suggest the L1 mAb OV52.24 as
      a candidate to be further developed for drug-delivery to cancer cells, while L1
      9.3 may be optimized to tag the tumor cells and stimulate immunogenic cancer cell
      killing. Furthermore, when analyzing cell-to-cell variability, we observed L1 mAb
      OV52.24 rapidly transition into a subpopulation with high-internalization
      capacity. In summary, this novel high-content method for measuring antibody
      internalization rate provides a high level of accuracy and sensitivity for cell
      population measurements and reveals further biologically relevant information
      when taking into account cellular heterogeneity. 

PMID- 25967951
TI  - Uncovering Leishmania-macrophage interplay using imaging flow cytometry.
AB  - Host-pathogen interaction is an area of considerable interest. Intracellular
      parasites such as Leishmania reside inside phagocytes such as macrophages,
      dendritic cells and neutrophils. Macrophages can be activated by cytokines such
      as IFN-gamma and Toll like receptor (TLR) agonists resulting in enhanced
      microbicidal activity. Leishmania parasites hijack the microbicidal function of
      macrophages, mainly by interfering with intracellular signaling initiated by IFN
      gamma and TLR ligands. Here we used transgenic Leishmania donovani parasites
      expressing the red fluorescent protein DsRed2 and imaging-flow cytometry
      technology to evaluate parasitic loads inside the macrophage in vitro. Further,
      this methodology enables us to visualize impairment in NFkappaB translocation to
      the nucleus in L. donovani infected macrophages. Additionally we show that
      uninfected bystander macrophages have a similar impairment in NFkappaB
      translocation as in L. donovani infected macrophages in response to the TLR4
      agonist LPS. This evidence suggests a possible immunosuppressive role for
      infected macrophages in regulating the activation of uninfected bystander
      macrophages. 

PMID- 25967952
TI  - Quantitating MHC class II trafficking in primary dendritic cells using imaging
      flow cytometry.
AB  - Presentation of antigenic peptides in MHC class II (MHCII) on dendritic cells
      (DCs) is the first step in the activation of antigen-specific CD4(+)T cells. The
      expression of surface MHCII-peptide complexes is tightly regulated as the
      frequency of MHCII-peptide complexes can affect the magnitude, as well as the
      phenotype of the ensuing CD4(+)T cell response. The surface MHCII-peptide levels
      are determined by the balance between expression of newly generated complexes,
      complex internalization, and their subsequent re-emergence or degradation.
      However, the molecular mechanisms that underpin these processes are still poorly
      understood. Here we describe a multispectral imaging flow cytometry assay to
      visualize MHCII trafficking that can be used as a tool to dissect the molecular
      mechanisms that regulate MHCII homeostasis in primary mouse and human DCs. 

PMID- 25967953
TI  - Activated Hemostatic Biomarkers in Patients with Implanted Left Ventricle Assist
      Devices: Are Heparin and/or Clopidogrel Justified?
AB  - BACKGROUND: Adequate anticoagulation represents a major problem for left
      ventricle assist device (LVAD) utilization in patients awaiting heart
      transplantation as well as for regeneration of the native heart. The proper
      management of hemostatic abnormalities during LVAD support may improve survival
      by reducing the incidence of hemorrhagic and/or thromboembolic complications.
      CASE REPORT: A 40-year-old man with implanted pulsatile LVAD due to dilated
      cardiomyopathy received aspirin and warfarin. The patient underwent serial weekly
      monitoring of hemostatic biomarkers including international normalization ratio,
      prothrombin time, prothrombin activity, activated partial thromboplastin time,
      fibrinogen, D-dimer, platelet aggregation induced by adenosine diphosphate and
      arachidonic acid, platelet count, and mean platelet volume. The external pump was
      exchanged three times - twice because of a clot formation in the blood chamber of
      the pump, and once according to the standard protocol. RESULTS: LVAD use was
      consistently associated with enhanced adenosine diphosphate-induced platelet
      aggregation independent from the timing of clot formation or external pump
      exchange. Among coagulation indices, increased D-dimer holds predictive value for
      clot formation. The fibrinogen level peaked before the first pump exchange and
      was twice as high than the average values. Gradual improvement in exercise
      capacity was observed 2 years after implantation, after which the patient
      underwent a controlled stress test in the stop mode of the LVAD and the device
      was successfully explanted. CONCLUSIONS: Serial assessment of hemostatic
      biomarkers may benefit and triage LVAD patients. Consistent platelet activation
      during long-term LVAD may justify the addition of clopidogrel, while high D-dimer
      and/or elevated fibrinogen may indicate adding heparin to the conventional
      antithrombotic regimen. Randomized evidence is needed to test such a hypothesis.

PMID- 25967954
TI  - Functional MRI in medulloblastoma survivors supports prophylactic reading
      intervention during tumor treatment.
AB  - Development of reading skills is vulnerable to disruption in children treated for
      brain tumors. Interventions, remedial and prophylactic, are needed to mitigate
      reading and other learning difficulties faced by survivors. A functional magnetic
      resonance imaging (fMRI) study was conducted to investigate long-term effects of
      a prophylactic reading intervention administered during radiation therapy in
      children treated for medulloblastoma. The fMRI study included 19 reading
      intervention (age 11.7 +/- 0.6 years) and 21 standard-of-care (age 12.1 +/- 0.6
      years) medulloblastoma survivors, and 21 typically developing children (age 12.3
      +/- 0.6 years). The survivors were 2.5 [1.2, 5.4] years after completion of tumor
      therapies and reading-intervention survivors were 2.9 [1.6, 5.9] years after
      intervention. Five fMRI tasks (Rapid Automatized Naming, Continuous Performance
      Test using faces and letters, orthographic and phonological processing of letter
      pairs, implicit word reading, and story reading) were used to probe reading
      related neural activation. Woodcock-Johnson Reading Fluency, Word Attack, and
      Sound Awareness subtests were used to evaluate reading abilities. At the time of
      fMRI, Sound Awareness scores were significantly higher in the reading
      intervention group than in the standard-of-care group (p = 0.046). Brain
      activation during the fMRI tasks was detected in left inferior frontal, temporal,
      ventral occipitotemporal, and subcortical regions, and differed among the groups
      (p < 0.05, FWE). The pattern of group activation differences, across brain areas
      and tasks, was a normative trend in the reading-intervention group. Standardized
      reading scores and patterns of brain activation provide evidence of long-term
      effects of prophylactic reading intervention in children treated for
      medulloblastoma.

PMID- 25967955
TI  - Continuous Flow Device Support in Children Using the HeartWare HVAD: 1,000 Days
      of Lessons Learned From a Single Center Experience.
AB  - The purpose of this study is to provide a single center experience with a
      continuous flow device in adolescents with end-stage heart failure. A
      retrospective single center analysis of patients aged 18 years or younger
      implanted with HVAD (HeartWare Inc, Framingham, MA) between October 2012 and
      March 2014 was performed. Demographics, preimplant and postimplant clinical data,
      survival, and adverse events (AEs) were recorded. A matched group of adults based
      on diagnosis, body surface area (BSA), and time period were used for outcome
      comparisons. Six adolescents with dilated cardiomyopathy were implanted with the
      HVAD. Median age and BSA were 13.4 years and 1.45 m2, respectively. All were
      Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS)
      profile-1 or profile-2. Median days on device were 108 with total patient-days on
      device of 1,017. Four adolescents were discharged home on device all in New York
      Heart Association 1. Five underwent transplantation with 100% survival. There
      were 18 AEs with one AE per 170 days on device. Compared with the adult cohort (n
      = 5), there was no difference in 1 year survival (p = 0.32). HVAD support in
      adolescents is highly successful as a bridge to transplantation. It provides
      early rehabilitation and improvement in quality of life. Morbidity is not
      negligible but appears comparable with that seen in adults.

PMID- 25967956
TI  - A severe systemic presentation of pigmented villonodular synovitis in a child
      with underlying Chediak-Higashi syndrome.
AB  - Pigmented villonodular synovitis (PVNS), a condition of synovial
      hyperproliferation that mostly affects large joints, is rare in children and
      conventionally lacks systemic symptoms. This report describes a complex
      paediatric patient who underwent bone marrow transplantation to control the
      accelerated phase of the Chediak-Higashi syndrome. Diffuse PVNS developed in one
      knee 2.75 years later. Progression of PVNS was accompanied by the development of
      severe systemic symptoms, which resolved rapidly following subtotal surgical
      debridement. The patient remains well with minimal elevation of inflammatory
      marker levels 10.5 years later. As PVNS and Chediak-Higashi syndrome are both
      very rare diseases we propose a potential unifying hypothesis for this
      combination. 

PMID- 25967957
TI  - Paediatric ENT standards in London: are we delivering a first-class service? a
      repeat audit.

PMID- 25967958
TI  - An Analysis of Prognostic Factors in Patients with Ovarian Malignant Germ Cell
      Tumors Who Are Treated with Fertility-Preserving Surgery.
AB  - BACKGROUND/AIMS: To analyze the clinicopathological factors that affect the
      prognosis and fertility of patients with malignant ovarian germ cell tumors
      (MOGCTs). METHODS: The medical records and follow-up data of 106 patients with
      MOGCTs who were treated at The Affiliated Tumor Hospital of Guangxi Medical
      University between January 1986 and December 2010 were enrolled in this study. A
      Kaplan-Meier analysis was used to analyze the survival curves. The different
      prognoses among the various clinicopathological factors were evaluated using a
      univariate analysis and a log-rank test. The multivariate analysis was performed
      using the Cox proportional hazard regression method. A logistic regression
      analysis was used to evaluate the influence of different factors on the prognoses
      and fertility. RESULTS: The median age at primary treatment was 22 years (range:
      9-61years). A total of 59 patients received fertility-preserving surgery, 45
      received radical surgery and 94 received postoperative adjuvant chemotherapy. The
      median follow-up time was 56.5 months (range: 2-309 months). A total of 11
      patients experienced a recurrence, and 23 patients died from their cancer. Of the
      47 patients who are alive without tumor, 45 have normal menstruation. Of the 39
      patients who wished to become pregnant, 31 patients had 33 successful pregnancies
      that resulted in 33 live births. No statistically significant difference (p >
      0.05) was observed with respect to the progression-free survival (PFS; 67.6 vs.
      63.3%), the overall survival (OS; 70 vs. 64.1%) and the mortality rate (15.3 vs.
      31.3%) between patients who received fertility-preserving surgery and those who
      received radical surgery. The univariate analysis showed that the pathological
      types, postoperative residual tumor size, lymph node resection, and omental
      resection were associated with OS (p < 0.1), whereas postoperative residual tumor
      size, number of chemotherapy cycles, lymph node resection, and omental resection
      were associated with PFS (p < 0.1). The multivariate analysis showed that only
      the postoperative residual tumor size was an independent prognostic factor of OS,
      whereas the postoperative residual tumor size, number of chemotherapy cycles and
      lymph node resection were independent prognostic factors of PFS. No statistically
      significant difference (p > 0.05) was observed with respect to the OS, PFS and
      fertility between patients who received fertility-preserving surgery and those
      who were treated with or without comprehensive surgical staging. CONCLUSION:
      MOGCTs can achieve a good prognosis after surgery and chemotherapy. Postoperative
      residual tumor size was an independent prognostic factor of PFS and OS. Moreover,
      comprehensive surgical staging cannot improve the prognosis. Fertility-preserving
      surgery plus adjuvant chemotherapy appeared to have little or no effect on
      prognosis and fertility.

PMID- 25967959
TI  - Protective Effect of Spironolactone on Endothelial-to-Mesenchymal Transition in
      HUVECs via Notch Pathway.
AB  - BACKGROUND: Fibrosis results in excessive buildup of extracellular matrix
      proteins along with abnormalities in structure and is partly derived by a process
      involving transforming growth factor beta (TGF-beta) called endothelial-to
      mesenchymal transition (EndMT). We investigated whether the aldosterone receptor
      blocker spironolactone could abrogate TGF-beta-induced fibrosis in EndMT and the
      underlying mechanism. METHODS: Human umbilical vein endothelial cells (HUVECs)
      were divided into 5 groups for treatment: blank; vehicle control; TGF-beta (10
      ng/ml); spironolactone (1 MUM)+TGF-beta; and spironolactone+TGF-beta+DAPT (10
      MUM). Cell chemotaxis was assayed by transwell assay. The expression of CD31 and
      vimentin was determined by Immunofluorescence staining and western blot analysis.
      Notch1 protein level was detected by western blot analysis. RESULTS:
      Spironolactone significantly prevented TGF-beta-stimulated EndMT by down-regulate
      vimentin and up-regulate CD31 in HUVECs (p<0.01).It inhibited cell migration
      during EndMT (p<0.01). The protective effect of spironolactone against EndMT
      could be attenuated by blocking the Notch signal pathway with DAPT (p<0.01).
      Notch signaling was activated and cross-interacted with TGF-beta and
      spironolactone in regulating EndMT in HUVECs and reversed the spironolactone
      related signaling by abrogating the antifibrotic actions with decreased Notch1
      protein expression (p<0.01). CONCLUSION: Spironolactone may have a protective
      role in TGF-beta-induced EndMT in HUVECs mediated by the Notch signal pathway.

PMID- 25967960
TI  - Effect of sodium alginate addition to resveratrol on acute gouty arthritis.
AB  - OBJECTIVE: Resveratrol has been shown to exert anti-inflammatory and antioxidant
      effects, while sodium alginate is a common pharmaceutic adjuvant with
      antioxidative and immunomodulatory properties. We performed an animal study to
      investigate the effect of sodium alginate addition to resveratrol on acute gouty
      arthritis. METHODS: Twenty-four SPF Wistar mice were randomized to four groups
      receiving the combination of sodium alginate and resveratrol, resveratrol alone,
      colchicine, and placebo, respectively. Acute gouty arthritis was induced by
      injection of 0.05 ml monosodium urate (MSU) solution (25g/mL) into ankle joint
      cavity. IL-1beta, CCR5, and CXCL10 levels in both serum and synovial fluid were
      measured using ELISA. NLRP3 expression in the synovial tissues was measured using
      western plot. RESULTS: The combination of sodium alginate and resveratrol
      significantly reduced synovial levels of IL-1beta, CCR5, and CXCL10 when compared
      with colchicines, and all P values were less than 0.0001. The combination of
      sodium alginate and resveratrol was also superior to resveratrol in terms of both
      serum levels and synovial levels of IL-1beta, CCR5, and CXCL10. In addition,
      resveratrol, with or without sodium alginate, could reduce NLRP3 expression
      obviously in the synovial tissues. CONCLUSION: The combination of sodium alginate
      and resveratrol has better effect over colchicines in treating MSU-induced acute
      gouty arthritis.

PMID- 25967962
TI  - Chronic-leptin attenuates Cisplatin cytotoxicity in MCF-7 breast cancer cell
      line.
AB  - BACKGROUND/AIMS: Large-scale epidemiological studies support a correlation
      between obesity and breast cancer in postmenopausal women. Circulating leptin
      levels are increased in obese and it has been suggested to play a significant
      role in mammary tumor formation and progression. Moreover, regulation of
      oxidative stress is another important factor in both tumor development and
      responses to anticancer therapies. The aim of this study was to examine the
      relationship between oxidative stress and chronic leptin exposure. METHODS: We
      treated MCF-7 breast cancer cells with 100 ng/mL leptin for 10 days and analyzed
      cell growth, ROS production and oxidative damage, as well as, some of the main
      antioxidant systems. Furthermore, since the hyperleptinemia has been associated
      with a worse pathology prognosis, we decided to test the influence of leptin in
      response to cisplatin anticancer treatment. RESULTS: Leptin signalling increased
      cell proliferation but reduced ROS production, as well as, oxidative damage. We
      observed an upregulation of SIRT1 after leptin exposure, a key regulator of
      stress response and metabolism. Additionally, leptin counteracted cisplatin
      induced cytotoxicity in tumor cells, showing a decrease in cell death.
      CONCLUSION: Chronic leptin could contribute to the effective regulation of
      endogenous and treatment-induced oxidative stress, and it contributes to explain
      in part its proliferative effects.

PMID- 25967963
TI  - Pig BMSCs Transfected with Human TFPI Combat Species Incompatibility and Regulate
      the Human TF Pathway in Vitro and in a Rodent Model.
AB  - BACKGROUND: The activation of tissue factor (TF) is one of the major reasons for
      coagulation dysregulation after pig-to-primate xenotransplantation. Tissue factor
      pathway inhibitor (TFPI) is the most important inhibitor of TF. Studies have
      demonstrated species incompatibility between pig TFPI and human TF. METHODS: A
      pig-to-macaque heterotopic auxiliary liver transplantation model was established
      to determine the origin of activated TF. Chimeric proteins of human and pig TFPI
      were constructed to assess the role of Kunitz domains in species incompatibility.
      Immortalised pig bone marrow mesenchymal stem cells transfected with human TFPI
      were tested for their ability to inhibit clotting in vitro. RESULTS: TF from
      recipient was activated early after liver xenotransplantation. Pig TFPI Kunitz
      domain 2 bound human FXa, but Kunitz domain 1 did not effectively inhibit human
      TF/FVIIa. Immortalised pig bone marrow mesenchymal cells (BMSCs) transfected with
      human TFPI showed a prolonged recalcification time in vitro and in a rodent
      model. CONCLUSION: Recipient TF is relevant to dysregulated coagulation after
      xenotransplantation. Kunitz domain 1 plays the most important role in species
      incompatibility between pig TFPI and human TF, and clotting can be inhibited by
      human TFPI-transfected pig BMSCs. Our study shows a possible way to resolve the
      incompatibility of pig TFPI.

PMID- 25967961
TI  - Tiam1-Rac1 Axis Promotes Activation of p38 MAP Kinase in the Development of
      Diabetic Retinopathy: Evidence for a Requisite Role for Protein Palmitoylation.
AB  - BACKGROUND/AIMS: Evidence in multiple tissues, including retina, suggests
      generation of reactive oxygen species (ROS) and the ensuing oxidative stress as
      triggers for mitochondrial defects and cell apoptosis. We recently reported novel
      roles for Tiam1-Rac1-Nox2 axis in retinal mitochondrial dysfunction and cell
      death leading to the development of diabetic retinopathy. Herein, we tested the
      hypothesis that activation of p38 MAP kinase, a stress kinase, represents the
      downstream signaling event to Rac1-Nox2 activation in diabetes-induced metabolic
      stress leading to capillary cell apoptosis. METHODS: Activation of p38 MAP kinase
      was quantified by Western blotting in retinal endothelial cells incubated with
      high glucose (20 mM) for up to 96 hours, a duration where mitochondrial
      dysfunction and capillary cell apoptosis can be observed. NSC23766 and 2
      bromopalmitate (2-BP) were used to assess the roles of Tiam1-Rac1 and
      palmitoylation pathways, respectively. RESULTS: Activation of p38 MAP kinase was
      observed as early as 3 hours after high glucose exposure, and continued until 96
      hours. Consistent with this, p38 MAP kinase activation was significantly higher
      in the retina from diabetic mice compared to age-matched normal mice. NSC23766
      markedly attenuated hyperglycemia-induced activation of p38 MAP kinase. Lastly, 2
      BP inhibited glucose-induced Rac1, Nox2 and p38 MAP kinase activation in
      endothelial cells. CONCLUSIONS: Tiam1-Rac1-mediated activation of Nox2 and p38
      MAP kinase constitutes early signaling events leading to mitochondrial
      dysfunction and the development of diabetic retinopathy. Our findings also
      provide the first evidence to implicate novel roles for protein palmitoylation in
      this signaling cascade.

PMID- 25967965
TI  - Calcitonin-induced effects on amniotic fluid-derived mesenchymal stem cells.
AB  - BACKGROUND/AIMS: Mesenchymal stem cells from human amniotic fluid (huAFMSCs) can
      differentiate into multiple lineages and are not tumorigenic after
      transplantation, making them good candidates for therapeutic purposes. The aim
      was to determine the effects of calcitonin on these huAFMSCs during osteogenic
      differentiation, in terms of the physiological role of calcitonin in bone
      homeostasis. METHODS: For huAFMSCs cultured under different conditions, we
      assayed: expression of the calcitonin receptor, using immunolabelling techniques;
      proliferation and osteogenesis, using colorimetric and enzymatic assays;
      intracellular Ca(2+) and cAMP levels, using videomicroscopy and
      spectrophotometry. RESULTS: The calcitonin receptor was expressed in
      proliferating and osteo-differentiated huAFMSCs. Calcitonin triggered
      intracellular Ca(2+) increases and cAMP production. Its presence in cell medium
      also induced dose-dependent inhibitory effects on proliferation and increased
      osteogenic differentiation of huAFMSCs, as also indicated by enhancement of
      specific markers and alkaline phosphatase activity. CONCLUSIONS: These data show
      that huAFMSCs represent a potential osteogenic model to study in-vitro cell
      responses to calcitonin (and other members of the calcitonin family). This leads
      the way to the opening of new lines of research that will add new insight both in
      cell therapies and in the pharmacological use of these molecules.

PMID- 25967964
TI  - Telocytes in pregnancy-induced physiological liver growth.
AB  - BACKGROUND/AIMS: We previously documented the presence of Telocytes (TCs) in
      liver and further indicated the potential roles of TCs in liver regeneration
      after hepatectomy. Pregnancy-induced liver growth, other than liver regeneration
      after hepatectomy, is a physiological hepatic adaption to meet the enhanced
      nutritional and metabolic demands. However, the possible roles of TCs in
      pregnancy-induced liver growth remain unknown. METHODS: Pregnant mice were
      sacrificed at different time points (pregnancy day 0.5, 4.5, 8.5, 10.5, 12.5,
      14.5, 16.5, and 18.5). The liver weight was used to evaluate the liver growth
      during pregnancy. Hepatocytes proliferation was determined by albumin and 5
      ethynyl-2'- deoxyuridine (EdU) double immunostaining while TCs were counted by
      double immunolabeling for CD34/PDGFR-alpha. RESULTS: Pregnancy-induced liver
      growth was preceded by increased proliferation of hepatocytes at pregnancy day
      4.5, 8.5, 14.5 and 16.5. Furthermore, the number of TCs in liver detected by
      double immunolabeling for CD34/PDGFR-alpha was significantly increased at
      pregnancy day 4.5 and day 14.5, that was coincident with the occurrence of two
      peaks of hepatic cell proliferation during pregnancy. CONCLUSION: Our results
      suggest a possible relationship between TCs and hepatocyte proliferation in
      pregnancy-induced liver growth.

PMID- 25967966
TI  - 17beta-Estradiol and/or Estrogen Receptor beta Attenuate the Autophagic and
      Apoptotic Effects Induced by Prolonged Hypoxia Through HIF-1alpha-Mediated BNIP3
      and IGFBP-3 Signaling Blockage.
AB  - BACKGROUND/AIMS: The risk of heart disease is higher in males than in females.
      However, this advantage of females declines with increasing age, presumably a
      consequence of decreased estrogen secretion and malfunctioning of the estrogen
      receptor. We previously demonstrated that 17beta-estradiol (E2) prevents
      cardiomyocyte hypertrophy, autophagy and apoptosis via estrogen receptor alpha
      (ERalpha), but the effects of ERbeta on myocardial injury remained elusive. The
      present paper thus, investigated the cardioprotective effects of estrogen (E2)
      and ERbeta against hypoxia-induced cell death. METHODS: Transient transfection of
      Tet-On ERbeta gene construct was used to overexpress ERbeta in hypoxia-treated
      H9c2 cardiomyoblast cells. RESULTS: Our data revealed that IGF1R, Akt
      phosphorylation and Bcl-2 expression are enhanced by ERbeta in H9c2 cells.
      Moreover, ERbeta overexpression reduced accumulation of hypoxia-related proteins,
      autophagy-related proteins and mitochondria-apoptotic proteins and enhanced the
      protein levels of Bcl-2, pAkt and Bad under hypoxic condition. In neonatal rat
      ventricular myocytes (NRVMs), we observed that hypoxia induced cell apoptosis as
      measured by TUNEL staining, and E2 and/or ERbeta could totally abolish hypoxia
      induced apoptosis. The suppressive effects of E2 and/or ERbeta in hypoxia-treated
      NRVMs were totally reversed by ER antagonist, ICI. Taken together, E2 and/or
      ERbeta exert the protective effect through repressed hypoxia-inducible HIF
      1alpha, BNIP3 and IGFBP-3 levels to restrain the hypoxia-induced autophagy and
      apoptosis effects in H9c2 cardiomyoblast cells. CONCLUSION: The results suggest
      that females probably could tolerate better prolonged hypoxia condition than
      males, and E2/ERbeta treatment could be a potential therapy to prevent hypoxia
      induced heart damage."

PMID- 25967967
TI  - Autophagy protects renal tubular cells against ischemia / reperfusion injury in a
      time-dependent manner.
AB  - BACKGROUND/AIMS: Autophagy is a dynamic catabolic process that maintains cellular
      homeostasis. Whether it plays a role in promoting cell survival or cell death in
      the process of renal ischemia/reperfusion (I/R) remains controversial, partly
      because renal autophagy is usually examined at a certain time point. Therefore,
      monitoring of the whole time course of autophagy and apoptosis may help better
      understand the role of autophagy in renal I/R. METHODS: Autophagy and apoptosis
      were detected after mice were subjected to bilateral renal ischemia followed by 0
      h to 7-day reperfusion, exposure of TCMK-1 cells to 24-h hypoxia, and 2 to 24-h
      reoxygenation. The effect of autophagy on apoptosis was assessed in the presence
      of autophagy inhibitor 3-methyladenine (3-MA) and autophagy activator rapamycin.
      RESULTS: Earlier than apoptosis, autophagy increased from 2-h reperfusion,
      reached the maximum at day 2, and then began declining from day 3 when renal
      damage had nearly recovered to normal. Exposure to 24-h hypoxia induced autophagy
      markedly, but it decreased drastically after 4 and 8-h reoxygenation, which was
      accompanied with increased cell apoptosis. Inhibition of autophagy with 3-MA
      increased the apoptosis of renal tubular cells during I/R in vivo and
      hypoxia/reoxygenation (H/R) in vitro. In contrast, activation of autophagy by
      rapamycin significantly alleviated renal tissue damage and tubular cell apoptosis
      in the two models. CONCLUSION: Autophagy was induced in a time-dependent manner
      and occurred earlier than the onset of cell apoptosis as an early response that
      played a renoprotective role during renal I/R and cell H/R. Up-regulation of
      autophagy may prove to be a potential strategy for the treatment of acute kidney
      injury.

PMID- 25967968
TI  - Vitamin D and lung cancer risk: a comprehensive review and meta-analysis.
AB  - BACKGROUND/AIM: Vitamin D has been suggested to have important roles against
      cancer development. There were several published studies on the association
      between vitamin D and lung cancer risk, but not conclusive results were
      available. METHODS: To clarify the role of vitamin D in lung carcinogenesis, we
      performed a comprehensive review of the literature and a meta-analysis to
      evaluate the association of serum vitamin D levels and dietary vitamin D intake
      with lung cancer risk. Twelve studies (9 prospective cohort and 3 nested case
      control studies) with a total of 288,778 individuals were included. The summary
      relative risk (RR) with 95% confidence interval (CI) was used to assess lung
      cancer risk. RESULTS: Meta-analysis of total 12 studies showed that RR for the
      association of high vitamin D status with lung cancer was 0.84 (95%CI 0.78-0.90,
      P < 0.001). The RR of lung cancer for the highest versus lowest quintile of serum
      vitamin D levels was 0.83 (95%CI 0.77-0.90, P < 0.001). The RR of lung cancer for
      the highest versus lowest quintile of vitamin D intake was 0.89 (95%CI 0.74-1.06,
      P = 0.184). CONCLUSION: Current data suggest an inverse association between serum
      vitamin D and lung cancer risk. Further studies are needed to investigate the
      effect of vitamin D intake on lung cancer risk and to evaluate whether vitamin D
      supplementation can prevent lung cancer.

PMID- 25967969
TI  - The Functional Variant in the 3'UTR of PTPRT with the Risk of Esophageal Squamous
      Cell Carcinoma in a Chinese Population.
AB  - BACKGROUND/AIMS: PTPRT is an essential tumor suppressor that plays crucial roles
      in regulating the mechanisms of tumorigenesis. Polymorphisms in PTPRT have been
      reported associated with human longevity, but their association with the risk of
      esophageal squamous cell carcinoma (ESCC) has not been found so far. In this
      study, we focused on the miRNAs associated SNPs in the 3'-UTR of PTPRT to
      investigate the further relationship of the SNPs with miRNAs among Chinese ESCC
      patients. METHODS: We performed case-control study including 790 ESCC patients
      and 749 cancer-free controls. Genotyping, real time PCR assay, cell transfection
      and the dual luciferase reporter assay were used in our study. RESULTS: We found
      that patients suffering from smoking exposure, drinking exposure and the history
      of cancer indicated to be the susceptible population by comparing with controls.
      Besides, SNP rs2866943 in PTPRT 3'-UTR was involved in the occurrence of ESCC by
      acting as a protective factor while rs6029959 acting a risk factor. SNP rs2866943
      was also could be regulated by miR-218 which caused a down-regulation of PTPRT in
      patients with CT and TT genotype. Furthermore, the carriers of CT and TT genotype
      presented a small tumor size as well as the low probability of metastasis.
      CONCLUSION: Our findings have shown that the SNP rs2866943 in PTPRT 3'-UTR,
      through disrupting the regulatory role of miR-218 in PTPRT expression, rs2866943
      in PTPRT might act as a protective factor in the pathogenesis of ESCC.

PMID- 25967970
TI  - Cinnamaldehyde prevents endothelial dysfunction induced by high glucose by
      activating Nrf2.
AB  - BACKGROUND/AIMS: It is well documented that hyperglycemia-induced oxidative
      stress is an important causative factor of endothelial dysfunction.
      Cinnamaldehyde (CA) is a key flavor compound in cinnamon essential oil that can
      enhance the antioxidant defense against reactive oxygen species (ROS) by
      activating NF-E2-related factor 2 (Nrf2), which has been shown to have a
      cardiovascular protective effect, but its role in endothelial dysfunction induced
      by high glucose is unknown. METHODS: Dissected male C57BL/6J mouse aortic rings
      and HUVECs were cultured in normal glucose(NG 5.5 mM) or high glucose(HG 30.0 mM)
      DMEM treatment with or without CA (10 uM). RESULTS: Treatment with CA protected
      the endothelium relaxation, inhibited ROS generation and preserved nitric oxide
      (NO) levels in the endothelium of mouse aortas treated with high glucose . CA up
      regulated Nrf2 expression, promoted its translocation to the nucleus'and
      increased HO-1, NQO1, Catalase and Gpx1 expression under high glucose condition.
      The increased level of nitrotyrosine in HUVECs under high glucose was also
      attenuated by treatment with CA. Dihydroethidium (DHE) and DAF-2DA staining
      indicated that CA inhibited the ROS generation and preserved the NO levels in
      HUVECs, but these effects were reversed by Nrf2-siRNA in high glucose conditions.
      CONCLUSION: Our results indicated that CA protected endothelial dysfunction under
      high glucose conditions and this effect was mediated by Nrf2 activation and the
      up-regulation of downstream target proteins. CA administration may represent a
      promising intervention in diabetic patients who are at risk for vascular
      complications.

PMID- 25967971
TI  - Baicalein Inhibits MMPs Expression via a MAPK-Dependent Mechanism in
      Chondrocytes.
AB  - BACKGROUND: Baicalein is a flavonoid isolated from Scutellaria baicalensis
      Georgi. Here, we investigated the anti-osteoarthritic effect of baicalein in
      vitro and in vivo. METHODS: Interleukin-1 beta (IL-1beta)-induced chondrocytes
      were treated with different concentrations of baicalein, real-time PCR and ELISA
      were performed to detect the matrix metalloproteinases (MMPs) expression. Western
      blot was used to evaluate the mitogen-activated protein kinase (MAPK) expression.
      In experimental osteoarthritis (OA), rabbits were treated with baicalein, gross
      morphological and histological assessment was performed to evaluate the cartilage
      damage. RESULTS: Baicalein significantly reduced the expression of MMPs in vitro
      and in vivo. Moreover, baicalein significantly reduced the phosphorylation of p38
      and extracellular signal regulated kinase (ERK), but not of c-Jun N-terminal
      kinase (JNK). In addition, intra-articular injection of baicalein ameliorated the
      cartilage damage in a rabbit model of OA induced by anterior cruciate ligament
      transection (ACLT). CONCLUSIONS: The results indicate that baicalein may be
      considered as a potential agent for OA treatment.

PMID- 25967972
TI  - Tetramethylpyrazine Ameliorated Hypoxia-Induced Myocardial Cell Apoptosis via HIF
      1alpha/JNK/p38 and IGFBP3/BNIP3 Inhibition to Upregulate PI3K/Akt Survival
      Signaling.
AB  - BACKGROUND: Hemorrhagic shock (HS) is the major cause of death from trauma.
      Hemorrhagic shock may lead to cellular hypoxia and organ damage. Our previous
      findings showed that HS induced a cardiac apoptosis pathway and synergistically
      caused myocardial cell damage in diabetic rats under trauma-induced HS.
      Tetramethylpyrazine (TMP) is a major biologically active ingredient purified from
      the rhizome of Ligusticum wallichii (called Chuang Xiong in Chinese). Chuan Xiong
      rescued cells from synergistic cardiomyoblast cell injury under high-glucose (HG)
      conditions plus hypoxia. TMP is one of the most important active ingredients that
      elevated the survival rate in ischemic brain injury and prevented inducible NO
      synthase expression to have anti-inflammatory effects against cell damage in
      different cell types. METHOD: Here, we further investigate whether TMP can
      protect against hypoxic (<1% oxygen) conditions in H9c2 cardiomyoblast cells for
      24 hrs. RESULTS: Our results showed that hypoxia mediated through HIF
      1alpha/JNK/p38 activation significantly elevated the levels of the hypoxia
      related proteins HIF-1alpha, BNIP3 and IGFBP3, further enhanced the pro-apoptotic
      protein Bak and upregulated downstream Caspase 9 and 3, resulting in cell death.
      All of these phenomena were fully recovered under TMP treatment. We observed that
      TMP exerted this effect by activating the IGF1 receptor survival pathway,
      dependent primarily on PI3K/Akt. When PI3K (class I) was blocked by specific
      siRNA, the hypoxia-induced activated caspase 3 and cell apoptosis could not be
      reversed by TMP treatment. CONCLUSION: Our results strongly suggest that TMP
      could be used to restore hypoxia-induced myocardial cell apoptosis and cardiac
      hypoxic damage.

PMID- 25967973
TI  - Curcumin Protects -SH Groups and Sulphate Transport after Oxidative Damage in
      Human Erythrocytes.
AB  - BACKGROUND/AIMS: Erythrocytes, continuously exposed to oxygen pressure and toxic
      compounds, are sensitive to oxidative stress, namely acting on integral Band 3
      protein, with consequences on cell membranes deformability and anion transport
      efficiency. The aim of the present investigation, conducted on human
      erythrocytes, is to verify whether curcumin (1 or 10uM), a natural compound with
      proved antioxidant properties, may counteract Band 3-mediated anion transport
      alterations due to oxidative stress. METHODS: Oxidative conditions were induced
      by exposure to, alternatively, either 2 mM N-ethylmaleimide (NEM) or pH-modified
      solutions (6.5 and 8.5). Rate constant for SO4(=) uptake and -SH groups
      estimation were measured to verify the effect of oxidative stress on anion
      transport efficiency and erythrocyte membranes. RESULTS: After the exposure of
      erythrocytes to, alternatively, NEM or pH-modified solutions, a significant
      decrease in both rate constant for SO4(=) uptake and -SH groups was observed,
      which was prevented by curcumin, with a dose-dependent effect. CONCLUSIONS: Our
      results show that: i) the decreased efficiency of anion transport may be due to
      changes in Band 3 protein structure caused by cysteine -SH groups oxidation,
      especially after exposure to NEM and pH 6.5; ii) 10 uM Curcumin is effective in
      protecting erythrocytes from oxidative stress events at level of cell membrane
      transport.

PMID- 25967974
TI  - Enhanced M1 and Impaired M2 Macrophage Polarization and Reduced Mitochondrial
      Biogenesis via Inhibition of AMP Kinase in Chronic Kidney Disease.
AB  - BACKGROUND: Macrophage polarization plays a pivotal role in the process of
      inflammation which is common in chronic kidney disease (CKD). Macrophages
      polarization under the condition of CKD remains poorly understood. Here we tested
      the hypothesis that CKD promotes macrophage M1 polarization. METHODS: A rat model
      of CKD was established by reduced renal mass (RRM). Polarization of macrophages
      was induced in ex vivo macrophages from RRM rats and cultured ones under the
      condition of uremic serum. The markers were evaluated by RT-PCR, western blot,
      and flow cytometer. RESULTS: Our data showed that macrophages from RRM rats
      displayed enhanced M1 and impaired M2 polarization as revealed by increased M1
      markers (tumor necrosis factor alpha, IL-6, IL-12p40, nitric oxide) and decreased
      M2 markers (IL-10, CD206, arginase activity) in response to LPS and IL-4
      induction, respectively. Treatment with uremic sera in peritoneal and bone marrow
      derived macrophages from normal rats led to similar results. Moreover,
      macrophages from RRM rats and cultured under the condition of uremic sera had
      reduced mitochondrial biogenesis. The disturbed macrophage polarization and
      mitochondrial biogenesis were accompanied by reduced activity of adenosine
      monophosphate-activated protein (AMP)-activated kinase (AMPK). Enhancing
      activation of AMPK restored mitochondrial biogenesis and M2 macrophage
      polarization. CONCLUSION: These observations suggest that CKD disturbs macrophage
      polarization and mitochondrial biogenesis through inhibition of AMPK. This might
      provide a novel therapeutic strategy for intervention of chronic inflammation in
      CKD.

PMID- 25967975
TI  - Dexmedetomidine attenuates blood-spinal cord barrier disruption induced by spinal
      cord ischemia reperfusion injury in rats.
AB  - BACKGROUND/AIMS: Dexmedetomidine has beneficial effects on ischemia reperfusion
      (I/R) injury to the spinal cord, but the underlying mechanisms are not fully
      understood. This study investigated the effects and possible mechanisms of
      dexmedetomidine on blood-spinal cord barrier (BSCB) disruption induced by spinal
      cord I/R injury. METHODS: Rats were intrathecally pretreated with dexmedetomidine
      or PBS control 30 minutes before undergoing 14-minute occlusion of aortic arch.
      Hind-limb motor function was assessed using Tarlov criteria, and motor neurons in
      the ventral gray matter were counted by histological examination. The
      permeability of the BSCB was examined using Evans blue (EB) as a vascular tracer.
      The spinal cord edema was evaluated using the wet-dry method. The expression and
      localization of matrix metalloproteinase-9 (MMP-9), Angiopoietin-1 (Ang1) and
      Tie2 were assessed by western blot, real-time polymerase chain reaction, and
      immunofluorescence. RESULTS: Intrathecal preconditioning with dexmedetomidine
      minimized the neuromotor dysfunction and histopathological deficits, and
      attenuated EB extravasation after spinal cord I/R injury. In addition,
      dexmedetomidine preconditioning suppressed I/R-induced increase in MMP-9.
      Finally, Dexmedetomidine preconditioning enhanced the Ang1-Tie2 system activity
      after spinal cord I/R injury. CONCLUSIONS: Dexmedetomidine preconditioning
      stabilized the BSCB integrity against spinal cord I/R injury by inhibition of MMP
      9, and enhancing the Ang1-Tie2 system.

PMID- 25967976
TI  - Protein Phosphatase 1 Beta is Modulated by Chronic Hypoxia and Involved in the
      Angiogenic Endothelial Cell Migration.
AB  - BACKGROUND/AIM: Endothelial cell migration is required for physiological
      angiogenesis, but also contributes to various pathological conditions, including
      tumour vascularization. The mRNA expression of PP1cbeta, the beta isoform of the
      catalytic PP1 subunit, was shown to be upregulated in chronic hypoxia. Since
      hypoxia is a major regulator of angiogenesis, the potential role of PP1cbeta in
      angiogenesis was investigated. METHODS: We examined PP1cbeta protein level in
      pediatric heart following chronic hypoxia and found PP1cbeta upregulation in
      cyanotic compared with acyanotic myocardium. By treating HUVEC cells with hypoxia
      mimicking agent, PP1cbeta protein level increased with maximum at 8 hours. The
      effect of PP1cbeta pharmacological inhibition, knockdown and overexpression, on
      endothelial cell migration and morphogenesis, was examined using in vitro wound
      healing scratch assay and endothelial tube formation assay. The PP1cbeta
      knockdown effects on F-actin reorganization (phalloidin staining), focal adhesion
      formation (vinculin) and focal adhesion kinases (FAK) activation, were evaluated
      by immunocytochemical staining and immunoblotting with specific antibodies.
      RESULTS: PP1cbeta knockdown significantly reduces endothelial cell migration, but
      does not have any significant effect on endothelial tube formation. Endothelial
      cell migration in the knockdown group is restored to the control level upon
      consecutive transfection with PP1cbeta cDNA. PP1cbeta overexpression does not
      significantly affect endothelial cell migration. Furthermore, PP1cbeta knockdown
      induces profound cytoskeletal reorganization, loss of focal adhesion sites and
      impairment of focal adhesion kinases (FAK) activation. CONCLUSIONS: PP1cbeta is
      regulator of endothelial cell migration, which is critical in the angiogenic
      process. PP1cbeta inhibition reduces endothelial cell migration through focal
      adhesion turnover and actin polymerization pathways.

PMID- 25967977
TI  - Antidiabetic Effect of Salvianolic Acid A on Diabetic Animal Models via AMPK
      Activation and Mitochondrial Regulation.
AB  - BACKGROUND/AIMS: Diabetes mellitus (DM) characterized by hyperglycemia
      contributes to macrovascular and microvascular complications. Salvianolic acid A
      (SalA) is a polyphenolic compound isolated from the root of Salvia miltiorrhiza
      Bunge, which is a traditional Chinese medicine widely used to treat
      cardiovascular diseases. However, little is known about its antidiabetic effect.
      Our study aimed to investigate the in vivo and in vitro antidiabetic effect of
      SalA and the underlying mechanisms. METHODS: Alloxan-induced type 1 diabetic mice
      and high-fat diet (HFD) and low-dose streptozotocin (STZ)-induced type 2 diabetic
      rats received SalA treatment. Blood glucose, oral glucose tolerance test (OGTT),
      24-h food and water intake were monitored. In vitro, glucose consumption and
      uptake were measured in HepG2 cells and L6 myotubes. Mitochondrial function was
      detected in hepatic and skeletal muscle mitochondria. AMP-activated protein
      kinase (AMPK) and Akt were analyzed by western blot. RESULTS: In both type 1 and
      type 2 diabetic animals, SalA lowered fasting blood glucose (FBG) and fed blood
      glucose in dose-dependent manner, as well as reduced 24-h food and water intake.
      In vitro, SalA caused dose-dependent increase in glucose consumption and enhanced
      glucose uptake. SalA significantly increased ATP production from 10 min to 12 h
      in HepG2 cells and L6 myotubes. Interestingly, SalA decreased mitochondrial
      membrane potential (MMP) in HepG2 cells. Furthermore, SalA improved hepatic and
      skeletal muscle mitochondrial function, increased ATP production, and
      concurrently decreased MMP. In particularly, SalA activated AMPK phosphorylation
      through Ca(2+)/calmodulin-dependent protein kinase kinase beta (CaMKKbeta)/AMPK
      signaling pathway, independent of liver kinase 1 (LKB1)/AMPK pathway. However,
      SalA didn't show any effect on insulin secretagogue and activation of PI3K/Akt
      signaling pathway. CONCLUSION: SalA exhibits the antidiabetic effects in diabetic
      animal models through improving mitochondrial function, increasing ATP
      production, and decreasing MMP via CaMKKbeta/AMPK signaling pathway.

PMID- 25967978
TI  - Unchanging pattern of prevalence of esophageal cancer, overall and by
      histological subtype, in the endoscopy service of the main referral hospital in
      the central region of Rio Grande do Sul State, in Southern Brazil.
AB  - Squamous cell carcinoma (SCC) and adenocarcinoma (ADC) are the two main
      histological types of esophageal cancer. Southern Brazil has the highest rates of
      esophageal cancer in South America, and the most prevalent subtype of esophageal
      cancer has been SCC. This study assessed the trend changes in the histological
      types of esophageal cancer, in a 20-year period, in the central region of Rio
      Grande do Sul State, Brazil. We searched all cases of esophageal cancer from 1993
      to 2012 by their histological diagnosis, grouping the patients in 4-year time
      periods to evaluate time trends. Among 18 441 upper gastrointestinal endoscopies
      we identified 686 cases of esophageal cancer. Histological study confirmed the
      diagnosis of SCC in 640 (93.3%) patients and ADC in 46 (6.7%). Overall, 522 men
      were diagnosed with esophageal carcinoma; from these, 489 (93.6%) presented SCC,
      and 33 (6.3%) ADC. Among women, 164 had the diagnosis of esophageal cancer, 151
      (92%) SCC, and 13 (7.9%) ADC. The proportion found among men and women was 3.1:1,
      respectively. The prevalence rate of esophageal cancer, along a 20 year-period,
      remained stable, as well as the rates of SCC and ADC. SCC was the most common
      type of esophageal cancer, and ADC presented very low prevalence. 

PMID- 25967979
TI  - Shaping the Reproductive System: Role of Semaphorins in Gonadotropin-Releasing
      Hormone Development and Function.
AB  - The semaphorin proteins, which contribute to the morphogenesis and homeostasis of
      a wide range of systems, are among the best-studied families of guidance cues.
      Much recent research has focused on the role of semaphorins in the development
      and adult activity of hormone systems and, reciprocally, how circulating
      reproductive hormones regulate their expression and function. Specifically,
      several reports have focused on the molecular mechanisms underlying the effects
      of semaphorins on the migration, survival and structural and functional
      plasticity of neurons that secrete gonadotropin-releasing hormone (GnRH),
      essential for the acquisition and maintenance of reproductive competence in
      mammals. Alterations in the development of this neuroendocrine system lead to
      anomalous or absent GnRH secretion, resulting in heterogeneous reproductive
      disorders such as congenital hypogonadotropic hypogonadism (CHH) or other
      conditions characterized by infertility or subfertility. This review summarizes
      current knowledge of the role of semaphorins and their receptors on the
      development, differentiation and plasticity of the GnRH system. In addition, the
      involvement of genetic deficits in semaphorin signaling in some forms of CHH in
      humans is discussed. 

PMID- 25967980
TI  - Determination and surveillance of nine acaricides and one metabolite in honey by
      liquid chromatography-tandem mass spectrometry.
AB  - A simple and accurate analytical method for the determination of acaricides in
      honey was developed and validated in accordance with Japanese validation
      guidelines. Analytes - amitraz, N-2,4-dimethylphenyl-N-methylformamidine (DMPF),
      etoxazole, fenpyroximate, fipronil, hexythiazox, propargite, pyridaben and
      spirodiclofen - were extracted with ethyl acetate under basic conditions and
      subsequently cleaned up using an InertSep((r)) MA-1 polymer-based anion-exchange
      column. The method was validated by fortified recovery tests at three different
      concentrations (1, 5 and 10 ug kg(-1)) performed with three samples daily on five
      different days. The method exhibited recoveries of 77-116% and precision
      (relative standard deviations - RSDs) of repeatability and within-laboratory
      reproducibility ranged from 2% to 22% and from 3% to 23%, respectively. The
      sample solution was successfully cleaned up to enable quantification using
      external solvent calibration curves. The limits of quantification (LOQs) were
      estimated to be 1 ug kg(-1) for all analytes. The method was applied to honey
      samples commercially available in Tokyo, Japan. Analysis of 250 honey samples
      indicated that amitraz was present in 127 samples, and that its residual
      concentration was less than 20 ug kg(-1). Propargite was detected in 23 samples
      at concentrations less than 1 ug kg(-1).

PMID- 25967981
TI  - Trienamine catalysis for asymmetric Diels-Alder reactions of 2,4-dienones: a
      theoretical investigation.
AB  - The mechanism and origin of the selectivity of asymmetric Diels-Alder reactions
      of 2,4-dienones (R1) by trienamine catalysis is investigated at the M06-2X/6
      311++G**(SMD, toluene)//B3LYP/6-311G** level. The acidic additive (salicylic acid
      or trifluoroacetic acid) promotes the isomerization of the ketoiminium ion into
      the key reactive cis-trienamine catalytic species with a preferred conformation
      by constructing a suitable hydrogen-bond bridge for a H shift. One-step
      cycloaddition was adopted for N-phenylmaleimide (R2), while a stepwise process
      was used for benzylidenecyanoacetate (R3) dienophile. The -CN and -CO2Et
      substituents in R3 may play an important role in forming a zwitterionic
      intermediate by participating in charge transfer by trienamine catalysis. The
      combination of a hydrogen bond from the protonated N atom of the tertiary amine
      and steric repulsion from the alpha-aryl group of trienamine makes the dienophile
      substrates approach the trienamine from one preferred face. The orbital factors
      define the most favored alignment of the trienamine and dienophile to realize the
      endo-selectivity of the product.

PMID- 25967982
TI  - Preformed Soluble Chemoreceptor Trimers That Mimic Cellular Assembly States and
      Activate CheA Autophosphorylation.
AB  - Bacterial chemoreceptors associate with the histidine kinase CheA and coupling
      protein CheW to form extended membrane arrays that receive and transduce
      environmental signals. A receptor trimers-of-dimers resides at each vertex of the
      hexagonal protein lattice. CheA is fully activated and regulated when it is
      integrated into the receptor assembly. To mimic these states in solution, we have
      engineered chemoreceptor cytoplasmic kinase-control modules (KCMs) based on the
      Escherichia coli aspartate receptor Tar that are covalently fused and trimerized
      by a foldon domain (Tar(FO)). Small-angle X-ray scattering, multi-angle light
      scattering, and pulsed-dipolar electron spin resonance spectroscopy of spin
      labeled proteins indicate that the Tar(FO) modules assemble into homogeneous
      trimers wherein the protein interaction regions closely associate at the end
      opposite to the foldon domains. The Tar(FO) variants greatly increase the
      saturation levels of phosphorylated CheA (CheA-P), indicating that the
      association with a trimer of receptor dimers changes the fraction of active
      kinase. However, the rate constants for CheA-P formation with the Tar variants
      are low compared to those for autophosphorylation by free CheA, and net
      phosphotransfer from CheA to CheY does not increase commensurately with CheA
      autophosphorylation. Thus, the Tar variants facilitate slow conversion to an
      active form of CheA that then undergoes stable autophosphorylation and is capable
      of subsequent phosphotransfer to CheY. Free CheA is largely incapable of
      phosphorylation but contains a small active fraction. Addition of Tar(FO) to CheA
      promotes a planar conformation of the regulatory domains consistent with array
      models for the assembly state of the ternary complex and different from that
      observed with a single inhibitory receptor. Introduction of Tar(FO) into E. coli
      cells activates endogenous CheA to produce increased clockwise flagellar
      rotation, with the effects increasing in the presence of the chemotaxis
      methylation system (CheB/CheR). Overall, the Tar(FO) modules demonstrate that
      trimerized signaling tips self-associate, bind CheA and CheW, and facilitate
      conversion of CheA to an active conformation.

PMID- 25967983
TI  - A web-based psychoeducational program for informal caregivers of patients with
      Alzheimer's disease: a pilot randomized controlled trial.
AB  - BACKGROUND: Although several face-to-face programs are dedicated to informal
      caregivers of persons with dementia, they are not always accessible to
      overburdened or isolated caregivers. Based on a face-to-face intervention
      program, we adapted and designed a Web-based fully automated psychoeducational
      program (called Diapason) inspired by a cognitive approach. OBJECTIVE: This study
      aimed to evaluate through a pilot unblinded randomized controlled trial the
      efficacy and acceptability of a Web-based psychoeducational program for informal
      caregivers of persons with Alzheimer's disease (PWAD) based on a mixed methods
      research design. METHODS: We recruited and randomized offline 49 informal
      caregivers of a PWAD in a day care center in Paris, France. They either received
      the Web-based intervention and usual care for 3 months (experimental group, n=25)
      or only usual care (control group, n=24). Caregivers' perceived stress (PSS-14,
      primary outcome), self-efficacy, burden, perceived health status, and depression
      (secondary outcomes) were measured during 3 face-to-face on-site visits: at
      baseline, at the end of the program (month 3), and after follow-up (month 6).
      Additionally, semistructured interviews were conducted with experimental group
      caregivers at month 6 and examined with thematic analysis. RESULTS: Intention-to
      treat analysis did not show significant differences in self-perceived stress
      between the experimental and control groups (P=.98). The experimental group
      significantly improved their knowledge of the illness (d=.79, P=.008) from
      baseline to month 3. Of the 25 participants allocated to the experimental group,
      17 (71%) finished the protocol and entirely viewed at least 10 of 12 online
      sessions. On average, participants used the website 19.72 times (SD 12.88) and
      were connected for 262.20 minutes (SD 270.74). The results of the satisfaction
      questionnaire showed that most participants considered the program to be useful
      (95%, 19/20), clear (100%, 20/20), and comprehensive (85%, 17/20). Significant
      correlations were found between relationship and caregivers' program opinion
      (P=.01). Thus, positive opinions were provided by husbands and sons (3/3),
      whereas qualified opinions were primarily reported by daughters (8/11). Female
      spouses expressed negative (2/3) or neutral opinions (1/3). Caregivers expected
      more dynamic content and further interaction with staff and peers. CONCLUSIONS:
      In this study, quantitative results were inconclusive owing to small sample size.
      Qualitative results indicated/showed little acceptance of the program and high
      expectations from caregivers. Caregivers did not rule out their interest in this
      kind of intervention provided that it met their needs. More dynamic,
      personalized, and social interventions are desirable. Our recruitment issues
      pointed out the necessity of in-depth studies about caregivers' help-seeking
      behaviors and readiness factors. TRIAL REGISTRATION: Clinicaltrials.gov
      NCT01430286; http://clinicaltrials.gov/ct2/show/NCT01430286 (Archived by WebCite
      at http://www.webcitation/6KxHaRspL).

PMID- 25967984
TI  - mRNA expression of dopamine receptors in peripheral blood lymphocytes of computer
      game addicts.
AB  - Excessive playing of computer games like some other behaviors could lead to
      addiction. Addictive behaviors may induce their reinforcing effects through
      stimulation of the brain dopaminergic mesolimbic pathway. The status of dopamine
      receptors in the brain may be parallel to their homologous receptors in
      peripheral blood lymphocytes (PBLs). Here, we have investigated the mRNA
      expression of dopamine D3, D4 and D5 receptors in PBLs of computer game addicts
      (n = 20) in comparison to normal subjects (n = 20), using a real-time PCR method.
      The results showed that the expression level of D3 and D4 dopamine receptors in
      computer game addicts were not statistically different from the control group.
      However, the expression of the mRNA of D5 dopamine receptor was significantly
      down-regulated in PBLs of computer game addicts and reached 0.42 the amount of
      the control group. It is concluded that unlike with drug addiction, the
      expression levels of the D3 and D4 dopamine receptors in computer game addicts
      are not altered compared to the control group. However, reduced level of the D5
      dopamine receptor in computer game addicts may serve as a peripheral marker in
      studies where the confounding effects of abused drugs are unwanted.

PMID- 25967985
TI  - Quantifying the utility of taking pills for preventing adverse health outcomes: a
      cross-sectional survey.
AB  - OBJECTIVES: The utility value attributed to taking pills for prevention can have
      a major effect on the cost-effectiveness of interventions, but few published
      studies have systematically quantified this value. We sought to quantify the
      utility value of taking pills used for prevention of cardiovascular disease
      (CVD). DESIGN: Cross-sectional survey. SETTING: Central North Carolina.
      PARTICIPANTS: 708 healthcare employees aged 18 years and older. PRIMARY AND
      SECONDARY OUTCOMES: Utility values for taking 1 pill/day, assessed using time
      trade-off, modified standard gamble and willingness-to-pay methods. RESULTS: Mean
      age of respondents was 43 years (19-74). The majority of the respondents were
      female (83%) and Caucasian (80%). Most (80%) took at least 2 pills/day. Mean
      utility values for taking 1 pill/day using the time trade-off method were: 0.9972
      (95% CI 0.9962 to 0.9980). Values derived from the standard gamble and
      willingness-to-pay methods were 0.9967 (0.9954 to 0.9979) and 0.9989 (95% CI
      0.9986 to 0.9991), respectively. Utility values varied little across
      characteristics such as age, sex, race, education level or number of pills taken
      per day. CONCLUSIONS: The utility value of taking pills daily in order to prevent
      an adverse CVD health outcome is approximately 0.997.

PMID- 25967986
TI  - Computerised clinical decision support systems to improve medication safety in
      long-term care homes: a systematic review.
AB  - OBJECTIVES: Computerised clinical decision support systems (CCDSS) are used to
      improve the quality of care in various healthcare settings. This systematic
      review evaluated the impact of CCDSS on improving medication safety in long-term
      care homes (LTC). Medication safety in older populations is an important health
      concern as inappropriate medication use can elevate the risk of potentially
      severe outcomes (ie, adverse drug reactions, ADR). With an increasing ageing
      population, greater use of LTC by the growing ageing population and increasing
      number of medication-related health issues in LTC, strategies to improve
      medication safety are essential. METHODS: Databases searched included MEDLINE,
      EMBASE, Scopus and Cochrane Library. Three groups of keywords were combined:
      those relating to LTC, medication safety and CCDSS. One reviewer undertook
      screening and quality assessment. RESULTS: Overall findings suggest that CCDSS in
      LTC improved the quality of prescribing decisions (ie, appropriate medication
      orders), detected ADR, triggered warning messages (ie, related to central nervous
      system side effects, drug-associated constipation, renal insufficiency) and
      reduced injury risk among older adults. CONCLUSIONS: CCDSS have received little
      attention in LTC, as attested by the limited published literature. With an
      increasing ageing population, greater use of LTC by the ageing population and
      increased workload for health professionals, merely relying on physicians'
      judgement on medication safety would not be sufficient. CCDSS to improve
      medication safety and enhance the quality of prescribing decisions are essential.
      Analysis of review findings indicates that CCDSS are beneficial, effective and
      have potential to improve medication safety in LTC; however, the use of CCDSS in
      LTC is scarce. Careful assessment on the impact of CCDSS on medication safety and
      further modifications to existing CCDSS are recommended for wider acceptance. Due
      to scant evidence in the current literature, further research on implementation
      and effectiveness of CCDSS is required.

PMID- 25967987
TI  - What is the association of smoking and alcohol use with the increase in social
      inequality in mortality in Denmark? A nationwide register-based study.
AB  - OBJECTIVES: The aim of this paper is to estimate the impact of smoking and
      alcohol use on the increase in social inequality in mortality in Denmark in the
      period 1985-2009. DESIGN: A nationwide register-based study. SETTING: Denmark.
      PARTICIPANTS: The whole Danish population aged 30 years or more in the period
      1985-2009. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome is
      mortality rates in relation to educational attainments calculated with and
      without deaths related to smoking and alcohol use. An absolute measure of
      inequality in mortality is applied along with a result on the direct contribution
      from smoking and alcohol use on the absolute difference in mortality rates. The
      secondary outcome is life expectancy in relation to educational attainments.
      RESULTS: Since 1985, Danish overall mortality rates have decreased. Alongside the
      improvement in mortality, the absolute difference in the mortality rate (per
      100,000 persons) between the lowest and the highest educated quartile grew from
      465 to 611 among men and from 250 to 386 among women. Smoking and alcohol use
      have caused 75% of the increase among men and 97% of the increase among women.
      Among men the increase was mainly caused by alcohol. In women the increase was
      mainly caused by smoking. CONCLUSIONS: The main explanation for the increase in
      social inequality in mortality since the mid-1980s is smoking and alcohol use. A
      significant reduction in the social inequality in mortality can only happen if
      the prevention of smoking and alcohol use are targeted to the lower educated part
      of the Danish population.

PMID- 25967989
TI  - Health Canada's use of its priority review process for new drugs: a cohort study.
AB  - OBJECTIVES: Priority reviews of new drug applications are resource intensive and
      drugs approved through this process have a greater likelihood of acquiring a
      serious safety warning compared to drugs approved through the standard process.
      Therefore, when Health Canada uses priority reviews, it is important that it
      accurately identifies products that represent a significant therapeutic advance.
      The purpose of this study is to compare Health Canada's use of priority reviews
      to therapeutic ratings from two independent organisations, the Patented Medicine
      Prices Review Board (PMPRB) and the French drug bulletin Prescrire International,
      over the period 1 January 1997-31 December 2012. DESIGN: Cohort study. DATA
      SOURCES: Annual reports of the Therapeutic Products Directorate, and the
      Biologics and Genetic Therapies Directorate; evaluations of therapeutic
      innovation from PMPRB and Prescrire International; WHO Collaborating Centre for
      Drug Statistics Methodology. INTERVENTIONS: Assessments by PMPRB and Prescrire
      International treated as a gold standard for postmarket therapeutic value.
      PRIMARY AND SECONDARY OUTCOME MEASURES: Drug-by-drug comparison between the
      review status from Health Canada and the therapeutic status from PMPRB/Prescrire
      using kappa values, and positive and negative predictive values. Analysis of the
      per cent of all new drug applications put into the priority review category over
      the 16-year period. RESULTS: Health Canada approved 426 new drugs, and 345 were
      evaluated by PMPRB and/or Prescrire. 91 had a priority review and 52 were
      assessed as innovative (p=0.0003). Agreement between Health Canada and
      PMPRB/Prescrire was only fair (kappa=0.330). The positive predictive value for
      Health Canada's review assignments was 36.3% and the negative predictive value
      was 92.5%. CONCLUSIONS: Health Canada's assignment of a priority approval to a
      new drug submission is only a fair predictor of the drug's therapeutic value once
      it is marketed. Health Canada should review its criteria for using priority
      reviews.

PMID- 25967988
TI  - Demographic and socioeconomic disparity in nutrition: application of a novel
      Correlated Component Regression approach.
AB  - OBJECTIVES: This study aimed to examine the most important demographic and
      socioeconomic factors associated with diet quality, evaluated in terms of
      compliance with national dietary recommendations, selection of healthy and
      unhealthy food choices, energy density and food variety. We hypothesised that
      different demographic and socioeconomic factors may show disparate associations
      with diet quality. STUDY DESIGN: A nationwide, cross-sectional, population-based
      study. PARTICIPANTS: A total of 1352 apparently healthy and non-institutionalised
      subjects, aged 18-69 years, participated in the Observation of Cardiovascular
      Risk Factors in Luxembourg (ORISCAV-LUX) study in 2007-2008. The participants
      attended the nearest study centre after a telephone appointment, and were
      interviewed by trained research staff. OUTCOME MEASURES: Diet quality as measured
      by 5 dietary indicators, namely, recommendation compliance index (RCI),
      recommended foods score (RFS), non-recommended foods score (non-RFS), energy
      density score (EDS), and dietary diversity score (DDS). The novel Correlated
      Component Regression (CCR) technique was used to determine the importance and
      magnitude of the association of each socioeconomic factor with diet quality, in a
      global analytic approach. RESULTS: Increasing age, being male and living below
      the poverty threshold were predominant factors associated with eating a high
      energy density diet. Education level was an important factor associated with
      healthy and adequate food choices, whereas economic resources were predominant
      factors associated with food diversity and energy density. CONCLUSIONS: Multiple
      demographic and socioeconomic circumstances were associated with different diet
      quality indicators. Efforts to improve diet quality for high-risk groups need an
      important public health focus.

PMID- 25967990
TI  - Evaluating holistic needs assessment in outpatient cancer care--a randomised
      controlled trial: the study protocol.
AB  - INTRODUCTION: People living with and beyond cancer are vulnerable to a number of
      physical, functional and psychological issues. Undertaking a holistic needs
      assessment (HNA) is one way to support a structured discussion of patients' needs
      within a clinical consultation. However, there is little evidence on how HNA
      impacts on the dynamics of the clinical consultation. This study aims to
      establish (1) how HNA affects the type of conversation that goes on during a
      clinical consultation and (2) how these putative changes impact on shared
      decision-making and self-efficacy. METHODS AND ANALYSIS: The study is hosted by
      10 outpatient oncology clinics in the West of Scotland and South West England.
      Participants are patients with a diagnosis of head and neck, breast, urological,
      gynaecological and colorectal cancer who have received treatment for their
      cancer. Patients are randomised to an intervention or control group. The control
      group entails standard care--routine consultation between the patient and
      clinician. In the intervention group, the patient completes a holistic needs
      assessment prior to consultation. The completed assessment is then given to the
      clinician where it informs a discussion based on the patient's needs and concerns
      as identified by them. The primary outcome measure is patient participation, as
      determined by dialogue ratio (DR) and preponderance of initiative (PI) within the
      consultation. The secondary outcome measures are shared decision-making and self
      efficacy. It is hypothesised that HNA will be associated with greater patient
      participation within the consultation, and that shared decision-making and
      feelings of self-efficacy will increase as a function of the intervention. ETHICS
      AND DISSEMINATION: This study has been given a favourable opinion by the West of
      Scotland Research Ethics Committee and NHS Research & Development. Study findings
      will be disseminated through peer-reviewed publications and conference
      attendance. TRAIL REGISTRATION NUMBER: Clinical Trials.gov NCT02274701.

PMID- 25967991
TI  - Evaluation of a complex, population-based injury claims management intervention
      for improving injury outcomes: study protocol.
AB  - INTRODUCTION: Injuries resulting from road traffic crashes are a substantial
      cause of disability and death worldwide. Injured persons receiving compensation
      have poorer recovery and return to work than those with non-compensable injury.
      Case or claims management is a critical component of injury compensation systems,
      and there is now evidence that claims management can have powerful positive
      impacts on recovery, but can also impede recovery or exacerbate mental health
      concerns in some injured people. This study seeks to evaluate the impact of a
      population-based injury claims management intervention in the State of Victoria,
      Australia, on the health of those injured in motor vehicle crashes, their
      experience of the compensation process, and the financial viability of the
      compensation system. METHODS AND ANALYSIS: Evaluation of this complex
      intervention involves a series of linked but stand-alone research projects to
      assess the anticipated process changes, impacts and outcomes of the intervention
      over a 5-year time frame. Linkage and analysis of routine administrative and
      health system data is supplemented with a series of primary studies collecting
      new information. Additionally, a series of 'action' research projects will be
      undertaken to inform the implementation of the intervention. A program logic
      model designed by the state government Transport Accident Commission in
      conjunction with the research team provides the evaluation framework. ETHICS AND
      DISSEMINATION: Relatively few studies have comprehensively examined the impact of
      compensation system processes on the health of injured persons, their
      satisfaction with systems processes, and impacts on the financial performance of
      the compensation scheme itself. The wholesale, population-based transformation of
      an injury claims management model is a rare opportunity to document impacts of
      system-level policy change on outcomes of injured persons. Findings will
      contribute to the evidence base of information on the public health effects of
      injury claims management policy and practice.

PMID- 25967992
TI  - Quantitative systematic review of the associations between short-term exposure to
      nitrogen dioxide and mortality and hospital admissions.
AB  - BACKGROUND: Short-term exposure to NO2 has been associated with adverse health
      effects and there is increasing concern that NO2 is causally related to health
      effects, not merely a marker of traffic-generated pollution. No comprehensive
      meta-analysis of the time-series evidence on NO2 has been published since 2007.
      OBJECTIVE: To quantitatively assess the evidence from epidemiological time-series
      studies published worldwide to determine whether and to what extent short-term
      exposure to NO2 is associated with increased numbers of daily deaths and hospital
      admissions. DESIGN: We conducted a quantitative systematic review of 204 time
      series studies of NO2 and daily mortality and hospital admissions for several
      diagnoses and ages, which were indexed in three bibliographic databases up to May
      2011. We calculated random-effects estimates by different geographic regions and
      globally, and also tested for heterogeneity and small study bias. RESULTS:
      Sufficient estimates for meta-analysis were available for 43 cause-specific and
      age-specific combinations of mortality or hospital admissions (25 for 24 h NO2
      and 18 of the same combinations for 1 h measures). For the all-age group, a 10
      ug/m(3) increase in 24 h NO2 was associated with increases in all-cause,
      cardiovascular and respiratory mortality (0.71% (95% CI 0.43% to 1.00%), 0.88%
      (0.63% to 1.13%) and 1.09% (0.75% to 1.42%), respectively), and with hospital
      admissions for respiratory (0.57% (0.33% to 0.82%)) and cardiovascular (0.66%
      (0.32% to 1.01%)) diseases. Evidence of heterogeneity between geographical region
      specific estimates was identified in more than half of the combinations analysed.
      CONCLUSIONS: Our review provides clear evidence of health effects associated with
      short-term exposure to NO2 although further work is required to understand
      reasons for the regional heterogeneity observed. The growing literature,
      incorporating large multicentre studies and new evidence from less well-studied
      regions of the world, supports further quantitative review to assess the
      independence of NO2 health effects from other air pollutants.

PMID- 25967993
TI  - Biomarkers of necrotising soft tissue infections: aspects of the innate immune
      response and effects of hyperbaric oxygenation-the protocol of the prospective
      cohort BIONEC study.
AB  - INTRODUCTION: The mortality and amputation rates are still high in patients with
      necrotising soft tissue infections (NSTIs). It would be ideal to have a set of
      biomarkers that enables the clinician to identify high-risk patients with NSTI on
      admission. The objectives of this study are to evaluate inflammatory and
      vasoactive biomarkers as prognostic markers of severity and mortality in patients
      with NSTI and to investigate whether hyperbaric oxygen treatment (HBOT) is able
      to modulate these biomarkers. The overall hypothesis is that plasma biomarkers
      can be used as prognostic markers of severity and mortality in patients with NSTI
      and that HBOT reduces the inflammatory response. METHODS AND ANALYSIS: This is a
      prospective, observational study being conducted in a tertiary referral centre.
      Biomarkers will be measured in 114 patients who have been operatively diagnosed
      with NSTI. On admission, baseline blood values will be obtained. Following
      surgery and HBOT, daily blood samples for measuring regular inflammatory and
      vasoactive biomarkers (pentraxin-3, interleukin-6 and nitrite) will be acquired.
      Samples will be analysed using validated ELISA assays, chemiluminescence and
      Griess reaction. Clinical data will be obtained during admission in the intensive
      care unit for a maximum of 7 days. The primary analysis will focus on pentraxin
      3, interleukin-6 and nitrite as early markers of disease severity in patients
      with NSTI. ETHICS AND DISSEMINATION: The study has been approved by the Regional
      Scientific Ethical Committee of Copenhagen (H-2-2014-071) and the Danish Data
      Protection Agency (J. no. 30-0900 and J. no. 30-1282). Results will be presented
      at national and international conferences and published in peer-reviewed
      scientific journals. TRIAL REGISTRATION: NCT02180906.

PMID- 25967994
TI  - Medical benefits in young adulthood: a population-based longitudinal study of
      health behaviour and mental health in adolescence and later receipt of medical
      benefits.
AB  - OBJECTIVES: To examine the extent to which smoking, alcohol, physical activity
      and mental health problems in 15-16-year-olds are associated with receipt of
      medical benefits in young adulthood, after adjustment for confounders. DESIGN:
      Prospective population-based cohort survey linked to national registers.
      PARTICIPANTS: In the 'Youth studies' from the Norwegian Institute of Public
      Health, 15 966 10th graders in 6 Norwegian counties answered a health behaviour
      and mental health questionnaire; 88% were linked to National Insurance
      Administration Registers (FD-Trygd). OUTCOME MEASURE: Time to receipt of medical
      benefits, based on FD-Trygd. Follow-up was from age 18 years until participants
      were aged 22-26 years. METHOD: We performed Cox regression analyses to examine
      the extent to which variations in health behaviour and mental health problems
      during 10th grade were associated with receipt of medical benefits during follow
      up. RESULTS: Daily smoking at age 15-16 years was associated with a significant
      increase in hazard of receiving health benefits at follow-up compared with not
      smoking for boys, HR (95% CI) 1.56 (1.23 to 1.98), and for girls 1.47 (1.12 to
      1.93). Physical activity was associated with a decrease in hazard compared with
      inactivity from 23% to 53% in boys and from 21% to 59% in girls, while use of
      alcohol showed a mixed pattern. The hazard for benefits use rose with increasing
      levels of emotional symptoms, peer problems, conduct problems and hyperactivity
      inattention problems (Strengths and Difficulties Questionnaire) at 15-16 years
      among both genders. CONCLUSIONS: Health behaviour and mental health problems in
      adolescence are independent risk factors for receipt of medical benefits in young
      adulthood.

PMID- 25967995
TI  - The Lisbon Cohort of men who have sex with men.
AB  - PURPOSE: Newly diagnosed HIV infections among men who have sex with men (MSM) are
      rising in many European countries. Surveillance tools must be tailored to the
      current state of the epidemic, and include decentralised prospective monitoring
      of HIV incidence and behavioural changes in key populations. In this scenario, an
      open prospective cohort study was assembled--The Lisbon Cohort of MSM--aiming to
      dynamically monitor the frequency of disease and its predictors. PARTICIPANTS:
      The Lisbon Cohort of MSM is an ongoing observational prospective study conducted
      at a community-based voluntary HIV counselling and testing centre in Lisbon,
      Portugal (CheckpointLX). Men testing negative for HIV, aged 18 or over and
      reporting having had sex with men are invited to follow-up visits every 6 months.
      At each evaluation, a face-to-face interview using a structured questionnaire is
      conducted, and HIV and syphilis rapid tests are performed by trained peer
      counsellors. From April 2011 to February 2014, 3106 MSM were eligible to the
      cohort of whom 923 (29.7%) did not participate. The remaining 2183 (70.3%) MSM
      were enrolled and 804 had at least one follow-up evaluation, for a total of 893
      person-years of observation. FUTURE PLANS: The study findings will be
      disseminated in peer-reviewed journals and presented at national and
      international conferences. The follow-up of this cohort of HIV-negative MSM will
      be a valuable tool for monitoring HIV incidence in a setting where limited
      prospective information existed. Moreover, it will allow for a deeper analytical
      approach to the study of population time trends and individual changes in risk
      factors that currently shape the HIV epidemic among MSM.

PMID- 25967996
TI  - Association between mobile phone use and self-reported well-being in children: a
      questionnaire-based cross-sectional study in Chongqing, China.
AB  - OBJECTIVES: In the past decade, the mobile phone (MP) has become extremely
      popular among children and the average age at which children own their first MP
      has decreased. The potential health effects of children's exposure to MP have
      been the subject of widespread public concern. The aim of our study is to
      investigate the associations between MP use and well-being in children. DESIGN:
      Cross-sectional study. SETTING: The questionnaires were completed in class with
      items regarding demographics, MP usage, self-reported well-being (symptoms were
      taken from the questionnaire of the HBSC survey) and possible confounding factors
      between October 2011 and May 2012 in Chongqing, China. Data were analysed using
      chi(2) tests and logistic regression models. PARTICIPANTS: Among the 793 children
      invited to participate, 781 returned the questionnaires. RESULTS: In total, 746
      (94.1%) valid questionnaires were received. Fatigue was significantly associated
      with the years of MP usage (OR 1.85; 95% CI 1.07 to 3.22) and the daily duration
      of MP calls (OR 2.98; 95% CI 1.46 to 6.12). Headache was significantly associated
      with the daily duration of MP calls (OR 2.85; 95% CI 1.23 to 6.57). However,
      after adjusting for confounders only, the association between fatigue and MP
      usage remained statistically significant. There was no significant association
      between MP use and other physical symptoms in children. CONCLUSIONS: The present
      study indicated that there was a consistent significant association between MP
      use and fatigue in children. Further in-depth research is needed to explore the
      potential health effects of MP use in children.

PMID- 25967997
TI  - Racial ethnic differences in type 2 diabetes treatment patterns and glycaemic
      control in the Boston Area Community Health Survey.
AB  - OBJECTIVES: Numerous studies continue to report poorer glycaemic control, and a
      higher incidence of diabetes-related complications among African-Americans and
      Hispanic-Americans as compared with non-Hispanic Caucasians with type 2 diabetes.
      We examined racial/ethnic differences in receipt of hypoglycaemic medications and
      glycaemic control in a highly insured Massachusetts community sample of
      individuals with type 2 diabetes. SETTING: Community-based sample from Boston,
      Massachusetts, USA. PARTICIPANTS: 682 patients with physician-diagnosed diabetes
      from the third wave of the Boston Area Community Health Survey (2010-2012). The
      study included approximately equal proportions of African-Americans, Hispanics
      and Caucasians. METHODS: We examined racial/ethnic disparities in diabetes
      treatment by comparing proportions of individuals on mutually exclusive diabetes
      treatment regimens across racial/ethnic subgroups. Using multivariable linear and
      logistic regression, we also examined associations between race/ethnicity and
      glycaemic control in the overall population, and within treatment regimens,
      adjusting for age, gender, income, education, health insurance, health literacy,
      disease duration, diet and physical activity. RESULTS: Among those treated (82%),
      the most commonly prescribed antidiabetic regimens were biguanides only (31%),
      insulin only (23%), and biguanides and insulin (16%). No overall racial/ethnic
      differences in treatment or glycaemic control (per cent difference for African
      Americans: 6.18, 95% CI -1.00 to 13.88; for Hispanic-Americans: 1.01, 95% CI 
      10.42 to 12.75) were observed. Within regimens, we did not observe poorer
      glycaemic control for African-Americans prescribed biguanides only, insulin only
      or biguanides combined with insulin/sulfonylureas. However, African-Americans
      prescribed miscellaneous regimens had higher risk of poorer glycaemic control
      (per cent difference=23.37, 95% CI 7.25 to 43.33). There were no associations
      between glycaemic levels and Hispanic ethnicity overall, or within treatment
      regimens. CONCLUSIONS: Findings suggest a lack of racial/ethnic disparities in
      diabetes treatment patterns and glycaemic control in this highly insured
      Massachusetts study population. Future studies are needed to understand impacts
      of increasing insurance coverage on racial/ethnic disparities in treatment
      patterns and related outcomes.

PMID- 25967998
TI  - Interventions for the prediction and management of chronic postsurgical pain
      after total knee replacement: systematic review of randomised controlled trials.
AB  - OBJECTIVES: Total knee replacement can be a successful operation for pain relief.
      However, 10-34% of patients experience chronic postsurgical pain. Our aim was to
      synthesise evidence on the effectiveness of applying predictive models to guide
      preventive treatment, and for interventions in the management of chronic pain
      after total knee replacement. SETTING: We conducted a systematic review of
      randomised controlled trials using appropriate search strategies in the Cochrane
      Library, MEDLINE and EMBASE from inception to October 2014. No language
      restrictions were applied. PARTICIPANTS: Adult patients receiving total knee
      replacement. INTERVENTIONS: Predictive models to guide treatment for prevention
      of chronic pain. Interventions for management of chronic pain. PRIMARY AND
      SECONDARY OUTCOME MEASURES: Reporting of specific outcomes was not an eligibility
      criterion but we sought outcomes relating to pain severity. RESULTS: No studies
      evaluated the effectiveness of predictive models in guiding treatment and
      improving outcomes after total knee replacement. One study evaluated an
      intervention for the management of chronic pain. The trial evaluated the use of a
      botulinum toxin A injection with antinociceptive and anticholinergic activity in
      49 patients with chronic postsurgical pain after knee replacement. A single
      injection provided meaningful pain relief for about 40 days and the authors
      acknowledged the need for a large trial with repeated injections. No trials of
      multidisciplinary interventions or individualised treatments were identified.
      CONCLUSIONS: Our systematic review highlights a lack of evidence about the
      effectiveness of prediction and management strategies for chronic postsurgical
      pain after total knee replacement. As a large number of people are affected by
      chronic pain after total knee replacement, development of an evidence base about
      care for these patients should be a research priority.

PMID- 25967999
TI  - What caused the outbreak of ESBL-producing Klebsiella pneumoniae in a neonatal
      intensive care unit, Germany 2009 to 2012? Reconstructing transmission with
      epidemiological analysis and whole-genome sequencing.
AB  - OBJECTIVE: We aimed to retrospectively reconstruct the timing of transmission
      events and pathways in order to understand why extensive preventive measures and
      investigations were not sufficient to prevent new cases. METHODS: We extracted
      available information from patient charts to describe cases and to compare them
      to the normal population of the ward. We conducted a cohort study to identify
      risk factors for pathogen acquisition. We sequenced the available isolates to
      determine the phylogenetic relatedness of Klebsiella pneumoniae isolates on the
      basis of their genome sequences. RESULTS: The investigation comprises 37 cases
      and the 10 cases with ESBL (extended-spectrum beta-lactamase)-producing K.
      pneumoniae bloodstream infection. Descriptive epidemiology indicated that a
      continuous transmission from person to person was most likely. Results from the
      cohort study showed that 'frequent manipulation' (a proxy for increased exposure
      to medical procedures) was significantly associated with being a case (RR 1.44,
      95% CI 1.02 to 2.19). Genome sequences revealed that all 48 bacterial isolates
      available for sequencing from 31 cases were closely related (maximum genetic
      distance, 12 single nucleotide polymorphisms). Based on our calculation of
      evolutionary rate and sequence diversity, we estimate that the outbreak strain
      was endemic since 2008. CONCLUSIONS: Epidemiological and phylogenetic analyses
      consistently indicated that there were additional, undiscovered cases prior to
      the onset of microbiological screening and that the spread of the pathogen
      remained undetected over several years, driven predominantly by person-to-person
      transmission. Whole-genome sequencing provided valuable information on the onset,
      course and size of the outbreak, and on possible ways of transmission.

PMID- 25968000
TI  - Classification of accelerometer wear and non-wear events in seconds for
      monitoring free-living physical activity.
AB  - OBJECTIVE: To classify wear and non-wear time of accelerometer data for
      accurately quantifying physical activity in public health or population level
      research. DESIGN: A bi-moving-window-based approach was used to combine
      acceleration and skin temperature data to identify wear and non-wear time events
      in triaxial accelerometer data that monitor physical activity. SETTING: Local
      residents in Swansea, Wales, UK. PARTICIPANTS: 50 participants aged under 16
      years (n=23) and over 17 years (n=27) were recruited in two phases: phase 1:
      design of the wear/non-wear algorithm (n=20) and phase 2: validation of the
      algorithm (n=30). METHODS: Participants wore a triaxial accelerometer (GeneActiv)
      against the skin surface on the wrist (adults) or ankle (children). Participants
      kept a diary to record the timings of wear and non-wear and were asked to ensure
      that events of wear/non-wear last for a minimum of 15 min. RESULTS: The overall
      sensitivity of the proposed method was 0.94 (95% CI 0.90 to 0.98) and specificity
      0.91 (95% CI 0.88 to 0.94). It performed equally well for children compared with
      adults, and females compared with males. Using surface skin temperature data in
      combination with acceleration data significantly improved the classification of
      wear/non-wear time when compared with methods that used acceleration data only
      (p<0.01). CONCLUSIONS: Using either accelerometer seismic information or
      temperature information alone is prone to considerable error. Combining both
      sources of data can give accurate estimates of non-wear periods thus giving
      better classification of sedentary behaviour. This method can be used in
      population studies of physical activity in free-living environments.

PMID- 25968001
TI  - Association between quality management and performance indicators in Dutch
      diabetes care groups: a cross-sectional study.
AB  - OBJECTIVES: To enhance the quality of diabetes care in the Netherlands, so-called
      care groups with three to 250 general practitioners emerged to organise and
      coordinate diabetes care. This introduced a new quality management level in
      addition to the quality management of separate general practices. We hypothesised
      that this new level of quality management might be associated with the aggregate
      performance indicators on the patient level. Therefore, we aimed to explore the
      association between quality management at the care group level and its aggregate
      performance indicators. DESIGN: A cross-sectional study. SETTING: All Dutch care
      groups (n=97). PARTICIPANTS: 23 care groups provided aggregate register-based
      performance indicators of all their practices as well as data on quality
      management measured with a questionnaire filled out by 1 or 2 of their quality
      managers. PRIMARY OUTCOMES: The association between quality management, overall
      and in 6 domains ('organisation of care', 'multidisciplinary teamwork', 'patient
      centredness', 'performance management', 'quality improvement policy' and
      'management strategies') on the one hand and 3 process indicators (the
      percentages of patients with at least 1 measurement of glycated haemoglobin,
      lipid profile and systolic blood pressure), and 3 intermediate outcome indicators
      (the percentages of patients with glycated haemoglobin below 53 mmol/mol (7%);
      low-density lipoprotein cholesterol below 2.5 mmol/L; and systolic blood pressure
      below 140 mm Hg) by weighted univariable linear regression. RESULTS: The domain
      'management strategies' was significantly associated with the percentage of
      patients with a glycated haemoglobin <53 mmol/mol (beta 0.28 (0.09; 0.46) p=0.01)
      after correction for multiple testing. The other domains as well as overall
      quality management were not associated with aggregate process or outcome
      indicators. CONCLUSIONS: This first exploratory study on quality management
      showed weak or no associations between quality management of diabetes care groups
      and their performance. It remains uncertain whether this second layer on quality
      management adds to better quality of care.

PMID- 25968002
TI  - A study of urgent and emergency referrals from NHS Direct within England.
AB  - OBJECTIVES: The presented study aimed to explore referral patterns of National
      Health Service (NHS) Direct to determine how patients engage with telephone-based
      healthcare and how telephone-based healthcare can manage urgent and emergency
      care. SETTING: NHS Direct, England, UK PARTICIPANTS: NHS Direct anonymised call
      data (N=1,415,472) were extracted over a representative 1-year period, during the
      combined month periods of July 2010, October 2010, January 2011 and April 2011.
      Urgent and emergency calls (N=269,558; 19.0%) were analysed by call factors and
      patient characteristics alongside symptom classification. Categorical data were
      analysed using the chi(2) test of independence with cross-tabulations used to
      test within-group differences. PRIMARY AND SECONDARY OUTCOME MEASURES: Urgent and
      emergency referrals to 999; accident and emergency or to see a general
      practitioner urgently, which are expressed as call rate per 100 persons per
      annum. Outcomes related to symptom variations by patient characteristics (age,
      gender, ethnicity and deprivation) alongside differences by patient
      characteristics of call factors (date and time of day). RESULTS: Urgent and
      emergency referrals varied by a range of factors relating to call, patient and
      symptom characteristics. For young children (0-4), symptoms related to 'crying'
      and 'colds and flu' and 'body temperature change' represented the significantly
      highest referrals to 'urgent and emergency' health services symptoms relating to
      'mental health' alongside 'pain' and 'sensation disorders' represented the
      highest referrals to urgent and emergency health services for adults aged 40+
      years. CONCLUSIONS: This study has highlighted characteristics of 'higher
      likelihood' referrals to urgent and emergency care through the delivery of a
      national nurse-led telephone healthcare service. This research can help
      facilitate an understanding of how patients engage with both in and out of hours
      care and the role of telephone-based healthcare within the care pathway.

PMID- 25968003
TI  - Association of child health and household amenities in high focus states in
      India: a district-level analysis.
AB  - OBJECTIVES: To assess household amenities in districts of high focus states and
      their association with child health in India. DESIGN: The data for the study are
      extracted from Annual Health Survey (AHS) and Census 2011. SETTINGS: Districts in
      high focus states in India. PARTICIPANTS: Information regarding children below 5
      years of age and women aged 15-49 has been extracted from the AHS (2010-2011),
      and household amenities information has been obtained from the Census (2011).
      MEASURES: Household amenities were assessed from the census at the district level
      in the high focus states. Child health indicators and wealth index were borrowed
      from AHS and used in this study to check their linkage with household amenities.
      RESULTS: Absence of drinking water from a treated source, improved sanitation,
      usage of clean cooking fuel and drainage facility in the household were adversely
      associated with the incidence of acute respiratory infection, diarrhoea, infant
      mortality rate (IMR) and under 5 mortality rate (U5MR). The mean IMR declined
      from 64 to 54 for districts where a high proportion of household have improved
      sanitation. The result of ordinary least square regression shows that improved
      sanitation has a negative and statistically significant association (beta=
      0.0067, p<0.01) with U5MR. CONCLUSIONS: Although child healthcare services are
      important in addressing child health issues, they barely touch on the root of the
      problem. Building toilets and providing safe drinking water, clean cooking fuel
      and drainage facilities at the household level, may prevent a number of adverse
      child health issues and may reduce the burden on the healthcare system in India.

PMID- 25968004
TI  - Effects of an internet-based cognitive behavioural therapy intervention on
      preventing major depressive episodes among workers: a protocol for a randomised
      controlled trial.
AB  - INTRODUCTION: The aim of this study is to examine the effects of an internet
      based cognitive behavioural therapy (iCBT) program on decreasing the risk of
      major depressive episodes (MDEs) among workers employed in a private corporate
      group in Japan, using a randomised controlled trial design. METHODS AND ANALYSIS:
      All of the workers in a corporate group (n=20,000) will be recruited through an
      invitation email. Participants who fulfil the inclusion criteria will be randomly
      allocated to intervention or control groups (planned N=4050 for each group). They
      will be allowed to complete the six lessons of the iCBT program within 10 weeks
      after the baseline survey. Those in the control group will receive the same iCBT
      after 12 months. The program includes several CBT skills: self-monitoring,
      cognitive restructuring, assertiveness, problem-solving and relaxation. The
      primary outcome measure is no new onset of MDE (using Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)/DSM-5
      criteria) during the 12-month follow-up. Assessment will use the web version of
      the WHO Composite International Diagnostic Interview V.3.0 depression section.
      ETHICS AND DISSEMINATION: The Research Ethics Review Board of Graduate School of
      Medicine, the University of Tokyo (No. 3083-(2)), approved the study procedures.
      TRIAL REGISTRATION NUMBER: The study protocol is registered at the UMIN Clinical
      Trials Registry (UMIN-CTR; ID=UMIN000014146).

PMID- 25968005
TI  - Exploratory clinical trial of combination wound therapy with a gelatin sheet and
      platelet-rich plasma in patients with chronic skin ulcers: study protocol.
AB  - INTRODUCTION: Chronic skin ulcers, such as diabetic ulcers, venous leg ulcers and
      pressure ulcers, are intractable and increasing in prevalence, representing a
      costly problem in healthcare. We developed a combination therapy with a gelatin
      sheet, capable of providing sustained release of platelet-rich plasma (PRP). The
      objective of this study is to investigate the safety and efficacy of autologous
      PRP covered with a hydrocolloid dressing and PRP covered with a gelatin sheet in
      the treatment of chronic skin ulcers. METHODS AND ANALYSIS: Thirty patients with
      chronic skin ulcers who have not healed with conventional therapy for at least 1
      month are being recruited. The patients will receive PRP after debridement, and
      the wounds will be covered with a hydrocolloid dressing or gelatin sheet. The
      efficacy will be evaluated according to the time from the beginning of PRP
      application to secondary healing or the day on which wound closure is achieved
      with a relatively simple surgical procedure, such as skin grafting or suturing.
      All patients will be followed up until 6 weeks after application to observe
      adverse events related to the application of PRP and the dressings. This study
      was designed to address and compare the safety and efficacy of PRP covered with a
      hydrocolloid dressing versus a gelatin sheet. If successful, this combination
      therapy may be an alternative to bioengineered skin substitutes containing living
      cells and lead to substantial progress in the management of chronic skin ulcers.
      ETHICS AND DISSEMINATION: The study protocol was approved by the Institutional
      Review Board of Kansai Medical University (KMU Number 0649-1, 4 August 2014:
      V.1.0). The findings of this trial will be disseminated through peer-reviewed
      journals, and national and international scientific meetings as well as to the
      patients. TRIAL REGISTRATION NUMBER: UMIN000015689.

PMID- 25968006
TI  - GlideScope video laryngoscopy versus direct laryngoscopy in the emergency
      department: a propensity score-matched analysis.
AB  - OBJECTIVE: To evaluate whether the use of a GlideScope video laryngoscope (GVL)
      improves first-attempt intubation success compared with the Macintosh
      laryngoscope (MAC) in the emergency department (ED). DESIGN: A propensity score
      matched analysis of data from a prospective multicentre ED airway registry-the
      Korean Emergency Airway Management Registry (KEAMR). SETTING: 4 academic EDs
      located in a metropolitan city and a province in South Korea. PARTICIPANTS: A
      total of 4041 adult patients without cardiac arrest who underwent emergency
      intubation from January 2007 to December 2010. OUTCOME MEASURES: The primary and
      secondary outcomes were successful first intubation attempt and intubation
      failure, respectively. To reduce the selection bias and potential confounding
      effects, we rigorously adjusted for the baseline differences between two groups
      using a propensity score matching. RESULTS: Of the 4041 eligible patients, a GVL
      was initially used in 540 patients (13.4%). Using 1:2 propensity score matching,
      363 and 726 patients were assigned to the GVL and MAC groups, respectively. The
      adjusted relative risks (95% CIs) for the first-attempt success rates with a GVL
      compared with a MAC were 0.76 (0.56 to 1.04; p=0.084) and the respective
      intubation failure rates 1.03(0.99 to 1.07; p=0.157). Regarding the subgroups,
      the first-attempt success of the senior residents and attending physicians was
      lower with the GVL (0.47 (0.23 to 0.98), p=0.043). In the patients with slight
      intubation difficulty, the first-attempt success was lower (0.60 (0.41 to 0.88),
      p=0.008) and the intubation failure was higher with the GVL (1.07 (1.02 to 1.13),
      p=0.008). CONCLUSIONS: In this propensity score-matched analysis of data from a
      prospective multicentre ED airway registry, the overall first-attempt intubation
      success and failure rates did not differ significantly between GVL and MAC in the
      ED setting. Further randomised controlled trials are needed to confirm our
      findings.

PMID- 25968007
TI  - The effect of blue-blocking intraocular lenses on circadian biological rhythm:
      protocol for a randomised controlled trial (CLOCK-IOL colour study).
AB  - INTRODUCTION: Blue light information plays an important role in synchronising
      internal biological rhythm within the external environment. Circadian
      misalignment is associated with the increased risk of sleep disturbance, obesity,
      diabetes mellitus, depression, ischaemic heart disease, stroke and cancer.
      Meanwhile, blue light causes photochemical damage to the retina, and may be
      associated with age-related macular degeneration (AMD). At present, clear
      intraocular lenses (IOLs) and blue-blocking IOLs are both widely used for
      cataract surgery; there is currently a lack of randomised controlled trials to
      determine whether clear or blue-blocking IOLs should be used. METHODS AND
      ANALYSIS: This randomised controlled trial will recruit 1000 cataract patients
      and randomly allocate them to receive clear IOLs or blue-blocking IOLs in a ratio
      of 1:1. The primary outcomes are mortality and the incidence of cardiovascular
      disease, cancer and AMD. Secondary outcomes are fasting plasma glucose,
      triglycerides, cholesterol, glycated haemoglobin, sleep quality, daytime
      sleepiness depressive symptoms, light sensitivity, the circadian rhythm of
      physical activity, wrist skin temperature and urinary melatonin metabolite.
      Primary outcomes will be followed until 20 years after surgery, and secondary
      outcomes will be assessed at baseline and 1 year after surgery. ETHICS AND
      DISSEMINATION: Ethical approval has been obtained from the Institutional Review
      Board of Nara Medical University (No. 13-032). The findings of this study will be
      communicated to healthcare professionals, participants and the public through
      peer-reviewed publications, scientific conferences and the University Hospital
      Medical Information Network Clinical Trials Registry (UMIN-CTR) home page. TRIAL
      REGISTRATION NUMBER: UMIN000014680.

PMID- 25968010
TI  - Diagnosis of Hemidiaphragmatic Paresis in a Preterm Infant with Transcutaneous
      Electromyography: A Case Report.
AB  - Transcutaneous electromyography of the diaphragm (dEMG) is a noninvasive and easy
      applicable tool to measure the electrical activity of the diaphragm. dEMG
      monitoring has recently been introduced in the neonatal intensive care unit as a
      novel cardiorespiratory monitor providing direct information on diaphragmatic
      breathing activity. We report a preterm infant with suspected paresis of the
      right diaphragm measured with transcutaneous dEMG, which showed a clear reduction
      in the electrical activity of the right-sided diaphragm. In conclusion, dEMG
      provides valuable information on regional diaphragmatic activity, which can
      assist the clinician in diagnosing hemidiaphragmatic paresis.

PMID- 25968011
TI  - Adaptive optics vision simulation and perceptual learning system based on a 35
      element bimorph deformable mirror.
AB  - An adaptive optics visual simulation combined with a perceptual learning (PL)
      system based on a 35-element bimorph deformable mirror (DM) was established. The
      larger stroke and smaller size of the bimorph DM made the system have larger
      aberration correction or superposition ability and be more compact. By simply
      modifying the control matrix or the reference matrix, select correction or
      superposition of aberrations was realized in real time similar to a conventional
      adaptive optics closed-loop correction. PL function was first integrated in
      addition to conventional adaptive optics visual simulation. PL training
      undertaken with high-order aberrations correction obviously improved the visual
      function of adult anisometropic amblyopia. The preliminary application of high
      order aberrations correction with PL training on amblyopia treatment was being
      validated with a large scale population, which might have great potential in
      amblyopia treatment and visual performance maintenance. 

PMID- 25968009
TI  - Therapeutic impact of repetitive transcranial magnetic stimulation (rTMS) on
      tinnitus: a systematic review and meta-analysis.
AB  - In this study, we conducted a systematic literature review and meta-analysis on
      the effect of repetitive transcranial magnetic stimulation (rTMS) compared with
      sham in chronic tinnitus patients. We searched databases, from their onset up to
      August 2014, for randomized controlled trials (RCT) in English that assessed the
      effectiveness of rTMS for chronic tinnitus. RCTs were selected according to
      inclusion/exclusion criteria before data were extracted. For the meta-analysis
      weighted mean differences (and standard deviations) of Tinnitus Questionnaire
      (TQ) and Tinnitus Handicap Inventory (THI) scores were determined. Therapeutic
      success was defined as difference of at least 7 points in the THI score between
      baseline and the follow-up assessment after treatment. The odds ratio (OR) for
      this variable was assessed. Results from 15 RCTs were analyzed. The mean
      difference for TQ score at 1 week after intervention was 3.42. For THI, the data
      of mean difference score in two groups, 1 and 6 month after intervention, was
      6.71 and 12.89, respectively. The all comparisons indicated a significant medium
      to large effect size in follow-up which is in favor of the rTMS. The pooled OR of
      therapeutic success of the studies which used THI at 1 month after intervention
      was 15.75. These data underscore the clinical effect of rTMS in the treatment of
      tinnitus. However, there is high variability of studies design and reported
      outcomes. Replication of data in multicenter trials with a large number of
      patients and long-term follow-up is needed before further conclusions can be
      drawn. 

PMID- 25968008
TI  - The Celiac Disease and Diabetes-Dietary Intervention and Evaluation Trial (CD
      DIET) protocol: a randomised controlled study to evaluate treatment of
      asymptomatic coeliac disease in type 1 diabetes.
AB  - INTRODUCTION: Coeliac disease (CD) is an autoimmune condition characterised by
      gluten-induced intestinal inflammation, and observed at a 5-10 fold greater
      prevalence in type 1 diabetes. While universal screening for CD in patients with
      diabetes is frequently advocated, objective data is limited as to benefits on
      diabetes control, bone health or quality of life related to the adoption of a
      gluten-free diet (GFD) in the large proportion of patients with diabetes with
      asymptomatic CD. The Celiac Disease and Diabetes-Dietary Intervention and
      Evaluation Trial (CD-DIET) study is a multicenter, randomised controlled trial to
      evaluate the efficacy and safety of a GFD in patients with type 1 diabetes with
      asymptomatic CD. METHODS AND ANALYSIS: Children and adults (8-45 years) with type
      1 diabetes will be screened for asymptomatic CD. Eligible patients with biopsy
      proven CD will be randomly assigned in a 1:1 ratio to treatment with a GFD for 1
      year, or continue with a gluten-containing diet. The primary outcome will
      evaluate the impact of the GFD on change in glycated haemoglobin. Secondary
      outcomes will evaluate changes in bone mineral density, blood glucose variability
      and health-related quality of life between GFD-treated and the regular diet group
      over a 1-year period. The study was initiated in 2012 and has subsequently
      expanded to multiple paediatric and adult centres in Ontario, Canada. ETHICS AND
      DISSEMINATION: The findings from this study will provide high-quality evidence as
      to the impact of GFD treatment on glycaemic control and complications in
      asymptomatic children and adults with CD and type 1 diabetes. TRIAL REGISTRATION
      NUMBER: NCT01566110.

PMID- 25968012
TI  - Aberrations measurement of freeform spectacle lenses based on Hartmann wavefront
      technology.
AB  - Freeform spectacle lenses have been popularized in the past few years.
      Traditional evaluation methods only focused on the refractive power parameters.
      The inspection technology of wavefront aberration has been introduced to
      optometry. In this paper, the wavefront aberration is used to evaluate the
      freeform spectacle lenses. The Shack-Hartmann wavefront technology is used to
      measure the same zones on the lenses with different designed forms. It shows that
      the aberration distributions are different from each other. The design with the
      freeform surface on the back can obtain the smallest aberrations in the entire
      surface. The aberrations on different zones for the same lens are analyzed. The
      blending zones show the greatest aberrations. The aberration on the progressive
      corridor is greater than the other zones. The Hartmann wavefront technology can
      be used to measure the wavefront aberration of freeform spectacle lenses. 

PMID- 25968013
TI  - Calibration method of microgrid polarimeters with image interpolation.
AB  - Microgrid polarimeters have large advantages over conventional polarimeters
      because of the snapshot nature and because they have no moving parts. However,
      they also suffer from several error sources, such as fixed pattern noise (FPN),
      photon response nonuniformity (PRNU), pixel cross talk, and instantaneous field
      of-view (IFOV) error. A characterization method is proposed to improve the
      measurement accuracy in visible waveband. We first calibrate the camera with
      uniform illumination so that the response of the sensor is uniform over the
      entire field of view without IFOV error. Then a spline interpolation method is
      implemented to minimize IFOV error. Experimental results show the proposed method
      can effectively minimize the FPN and PRNU. 

PMID- 25968014
TI  - Wideband slab photonic crystal waveguides for slow light using differential
      optofluidic infiltration.
AB  - A new type of wideband slow light with a large delay bandwidth product in a slab
      photonic crystal waveguide with a triangular lattice of circular air holes in a
      silicon-on-insulator substrate based on optofluidic infiltration is demonstrated.
      It is shown that dispersion engineering through infiltrating optical fluids-with
      different refractive indices n(1f) and n(2f)--in the first two rows of the air
      holes innermost to the waveguide results in an improved normalized delay
      bandwidth product ranging from 0.187 to 0.377 with large bandwidth (12 
      nm<Deltalambda<32  nm) and group index (14.20< n(g)< 24.62) around 1550 nm. The
      nearly zero group velocity dispersion on the order of 10-(20)  s(2)/m is achieved
      in all of the structures. These results are obtained by numerical simulation
      based on a three-dimensional-plane-wave expansion method.

PMID- 25968015
TI  - Vanishing tilt-to-length coupling for a singular case in two-beam laser
      interferometers with Gaussian beams.
AB  - The omnipresent tilt-to-length coupling in two-beam laser interferometers,
      frequently a nuisance in precision measurements, vanishes for the singular case
      of two beams with identical parameters and complete detection of both beams
      without clipping. This effect has been observed numerically and is explained in
      this manuscript by the cancellation of two very different effects of equal
      magnitude and opposite sign. 

PMID- 25968016
TI  - Measurement of fog and haze extinction characteristics and availability
      evaluation of free space optical link under the sea surface environment.
AB  - Fog and haze can lead to changes in extinction characteristics. Therefore, the
      performance of the free space optical link is highly influenced by severe weather
      conditions. Considering the influential behavior of weather conditions, a state
      of-the-art solution for the observation of fog and haze over the sea surface is
      presented in this paper. A Mie scattering laser radar, with a wavelength of 532
      nm, is used to observe the weather conditions of the sea surface environment. The
      horizontal extinction coefficients and visibilities are obtained from the
      observation data, and the results are presented in the paper. The changes in the
      characteristics of extinction coefficients and visibilities are analyzed based on
      both the short-term (6 days) severe weather data and long-term (6 months) data.
      Finally, the availability performance of the free space optical communication
      link is evaluated under the sea surface environment. 

PMID- 25968017
TI  - Broadband high-reflective distributed Bragg reflectors based on amorphous silicon
      films for semiconductor laser facet coatings.
AB  - We fabricated amorphous silicon (a-Si)-based distributed Bragg reflectors (DBRs)
      consisting of alternating dense/porous films (i.e., pair) for a center wavelength
      (lambda(c)) of 0.96 MUm by oblique angle deposition (OAD) technique using an
      electron-beam evaporation system. The dense (high refractive index, i.e., high-n)
      and porous (low-n) a-Si films were deposited at two incident vapor flux angles of
      0 degrees  and 80 degrees  in the OAD, respectively. Their optical reflectance
      characteristics were investigated in the wavelength range of 0.6-1.5 MUm,
      including theoretical comparison using a rigorous coupled-wave analysis method.
      Above three pairs, the reflectivity (R) of a-Si DBRs was almost saturated at
      wavelengths around 0.96 MUm, exhibiting R values of >97%. For the a-Si DBR with
      only three pairs, a broad normalized stop bandwidth (Deltalambda/lambda(c)) of
      ~22.5% was obtained at wavelengths of ~0.87-1.085  MUm, keeping high R values of
      >95%. To simply demonstrate the feasibility of device applications, the a-Si DBR
      with three pairs was coated as a high-reflection layer at the rear facet of
      GaAs/InGaAs quantum-well laser diodes (LDs) operating at lambda=0.96  MUm. For
      the LDs coated with three-pair a-Si DBR, external differential quantum efficiency
      (eta(d)) was nearly doubled compared to the uncoated LDs, indicating the eta(d)
      value of ~50.6% (i.e., eta(d)~25.5% for the uncoated LDs).

PMID- 25968018
TI  - Surface plasmon resonance-based fiber-optic hydrogen gas sensor utilizing
      palladium supported zinc oxide multilayers and their nanocomposite.
AB  - We analyze surface plasmon resonance-based fiber-optic sensor for sensing of
      small concentrations of hydrogen gas in the visible region of the electromagnetic
      spectrum. One of the two probes considered has multilayers of zinc oxide (ZnO)
      and palladium (Pd) while the other has layer of their composite over a silver
      coated unclad core of the fiber. The analysis is carried out for different volume
      fractions of palladium nanoparticles dispersed in zinc oxide host material in the
      nanocomposite layer. For the analysis, a Maxwell-Garnett model is adopted for
      calculating the dielectric function of a ZnO:Pd nanocomposite having
      nanoparticles of dimensions smaller than the wavelength of radiation used. The
      effects of the volume fraction of the nanoparticles in the nanocomposite and the
      thickness of the nanocomposite layer on the figure of merit of the sensor have
      been studied. The film thickness of the layer and the volume fraction of
      nanoparticles in the ZnO:Pd nanocomposite layer have been optimized to achieve
      the maximum value of the figure of merit of the sensor. It has been found that
      the figure of merit of the sensing probe coated with ZnO:Pd nanocomposite is more
      than twofold of the sensing probe coated with multilayers of Pd and ZnO over a
      silver coated unclad core of the fiber; hence, the sensor with a nanocomposite
      layer works better than that with multilayers of zinc oxide and palladium. The
      sensor can be used for online monitoring and remote sensing of hydrogen gas. 

PMID- 25968019
TI  - 8.5  W mode-locked Yb:Lu1.5Y1.5Al5O12 laser with master oscillator power
      amplifiers.
AB  - We report on a diode-pumped passively mode-locked Yb:Lu(1.5)Y(1.5)Al(5)O(12)
      (Yb:LuYAG) laser for the first time to our knowledge. With the mixed crystal of
      Yb:LuYAG as gain medium, the mode-locked laser generated 2.2 W of average output
      power with a repetition rate of 83.9 MHz and pulse duration of 2.4 ps at the
      wavelength of 1030 nm. In order to obtain higher output power, the output from
      the mode-locked oscillator was further amplified to 8.5 W by two-stage single
      pass amplifiers. The high-power picosecond laser is very useful for applications
      such as pumping of midinfrared optical parametric oscillators, material
      microprocessing, and UV light generation.

PMID- 25968020
TI  - Fast falling time of fringe-field-switching negative dielectric anisotropy liquid
      crystal achieved by inserting vertical walls.
AB  - We report a simulation result in which we obtained a faster falling time of the
      fringe-field-switching negative dielectric anisotropy liquid crystal (n-FFS) by
      segregating the subpixel area with vertical walls. By inserting walls near both
      edges of the interdigitated electrodes, the transmittance (TR) between the walls
      was increased by a large twist angle of the liquid crystal. The falling time of
      the n-FFS with 12 walls was 10.5 ms, about 50% less than the n-FFS without a wall
      (21.3 ms). The maximum TR (TR(max)) of the proposed n-FFS was 26.1%, which was
      slightly smaller than the TR(max) of the n-FFS without walls (27.8%) but still
      larger than the FFS with a positive dielectric anisotropy liquid crystal (p-FFS).

PMID- 25968021
TI  - All-optical compact surface plasmonic two-mode interference device for optical
      logic gate operation.
AB  - In this paper, we have proposed an ultra-compact surface plasmonic two-mode
      interference (SPTMI) coupler having a silicon core, silver upper and lower
      cladding, and GaAsInP left and right cladding for basic logic gate operations. By
      modulating the refractive index of the GaAsInP cladding with incidence of optical
      pulse energy, we have shown coupling characteristics depending on additional
      phase change DeltaPhi(E) between the excited surface plasmon polariton modes
      propagating through the silicon core. By using applied optical pulse dependent
      coupling behavior of the proposed SPTMI device, the operations of NOT, AND, and
      OR logic gates are shown. It is also seen that the coupling length of the
      proposed device is 32.3 times more compact than that of a multimode interference
      directional coupler. 

PMID- 25968022
TI  - Range-resolved detection of potassium chloride using picosecond differential
      absorption light detection and ranging.
AB  - A laser diagnostic concept for measurement of potassium chloride (KCl) and
      potentially other alkali compounds in large-scale boilers and furnaces of limited
      optical access is presented. Single-ended, range-resolved, quantitative detection
      of KCl is achieved by differential absorption light detection and ranging (DIAL)
      based on picosecond laser pulses. Picosecond DIAL results have been compared
      experimentally with line-of-sight measurements using a commercial instrument, the
      in situ alkali chloride monitor (IACM), utilizing differential optical absorption
      spectroscopy. For centimeter-scale range resolution and a collection distance of
      2.5 m, picosecond DIAL allowed for measurement of KCl concentrations around 130
      ppm at 1200 K, in good agreement with values obtained by IACM. The DIAL data
      indicate a KCl detection limit of around 30 ppm for the present experimental
      conditions. In addition, a double-pulse DIAL setup has been developed and
      demonstrated for measurements under dynamic conditions with strong Mie
      scattering. The picosecond DIAL results are discussed and related to possible
      implementations of the method for measurements in industrial environments.

PMID- 25968023
TI  - Testing a polarimetric cloud imager aboard research vessel Polarstern: comparison
      of color-based and polarimetric cloud detection algorithms.
AB  - Cloud cover estimation is an important part of routine meteorological
      observations. Cloudiness measurements are used in climate model evaluation,
      nowcasting solar radiation, parameterizing the fluctuations of sea surface
      insolation, and building energy transfer models of the atmosphere. Currently, the
      most widespread ground-based method to measure cloudiness is based on analyzing
      the unpolarized intensity and color distribution of the sky obtained by digital
      cameras. As a new approach, we propose that cloud detection can be aided by the
      additional use of skylight polarization measured by 180 degrees  field-of-view
      imaging polarimetry. In the fall of 2010, we tested such a novel polarimetric
      cloud detector aboard the research vessel Polarstern during expedition ANT
      XXVII/1. One of our goals was to test the durability of the measurement hardware
      under the extreme conditions of a trans-Atlantic cruise. Here, we describe the
      instrument and compare the results of several different cloud detection
      algorithms, some conventional and some newly developed. We also discuss the
      weaknesses of our design and its possible improvements. The comparison with cloud
      detection algorithms developed for traditional nonpolarimetric full-sky imagers
      allowed us to evaluate the added value of polarimetric quantities. We found that
      (1) neural-network-based algorithms perform the best among the investigated
      schemes and (2) global information (the mean and variance of intensity),
      nonoptical information (e.g., sun-view geometry), and polarimetric information
      (e.g., the degree of polarization) improve the accuracy of cloud detection,
      albeit slightly. 

PMID- 25968024
TI  - Error analysis for a laser differential confocal radius measurement system.
AB  - In order to further improve the measurement accuracy of the laser differential
      confocal radius measurement system (DCRMS) developed previously, a DCRMS error
      compensation model is established for the error sources, including laser source
      offset, test sphere position adjustment offset, test sphere figure, and motion
      error, based on analyzing the influences of these errors on the measurement
      accuracy of radius of curvature. Theoretical analyses and experiments indicate
      that the expanded uncertainty of the DCRMS is reduced to U=0.13  MUm+0.9  ppm.R
      (k=2) through the error compensation model. The error analysis and compensation
      model established in this study can provide the theoretical foundation for
      improving the measurement accuracy of the DCRMS. 

PMID- 25968025
TI  - Three-dimensional profilometry of microlenses by phase shifting interferometery
      using nematic liquid crystal material filled cell as a phase modulator.
AB  - In this paper, we report the use of a nematic liquid crystal material filled cell
      in transmission mode as a voltage controlled phase modulator for the
      characterization of microlenses. In one arm of the Mach-Zehnder interferometer, a
      nematic liquid crystal filled cell with DC voltage connection was placed, and in
      another arm of the interferometer microlenses with a 4-F imaging system were
      placed. Interference takes place between the light beams coming from the two arms
      of the Mach-Zehnder interferometer, one after passing through the nematic liquid
      crystal cell and another after passing through microlenses. Interference patterns
      were recorded by a CCD camera. By applying DC voltage to the nematic liquid
      crystal filled cell, various phase shifted interferograms were recorded, and from
      phase shifted interferograms, the shape and size of microlenses were determined.
      The results of the reconstructed profile of the microlenses are compared with
      white-light profilometry. 

PMID- 25968026
TI  - Spatial distribution characteristics of plasma plume on attenuation of laser
      radiation under subatmospheric pressure.
AB  - The attenuation of a laser by plasma plume can be restrained for laser welding
      under subatmospheric pressure. Based on the experimental obtained spectra, the
      extinctions of a probe laser under different subatmospheric pressures and the
      spatial distribution of probe laser extinction were measured. The role of
      subatmospheric pressure on plasma plume was analyzed. The results show that, with
      decreasing ambient pressure, the extinction of a probe laser decreases, and the
      welding penetration depth increases. The maximum attainable value of extinction
      gets far away from the keyhole in the transversal and vertical directions. The
      attenuation of a fiber laser is about 10% under normal atmosphere, and it reaches
      only about 1% when the ambient pressure is reduced to 3 kPa.

PMID- 25968027
TI  - Stereoscopic pyrometer for char combustion characterization.
AB  - For many pulverized fuels, especially coal and biomass, char combustion is the
      time determining step. Based on intensified ICCD cameras, a novel setup has been
      developed to study pulverized fuel combustion, mainly in a laminar flow reactor.
      For char burning characterization, the typical measurement parameters are
      particle temperature, size, and velocity. The working principle of the camera
      setup is introduced and its capabilities are discussed by examination of coal
      particle combustion under CO(2)-enriched, so-called oxy-fuel atmospheres with
      varying O(2) content.

PMID- 25968028
TI  - Humidity coefficient correction in the calculation equations of air refractive
      index by He-Ne laser based on phase step interferometry.
AB  - The refractive index of air (RIA) is an important parameter in precision
      measurement. The revisions to Edlen's equations by Boensch and Potulski
      [Metrologia 35, 133 (1998)] are mostly used to calculate the RIA at present.
      Since the humidity correction coefficients in the formulas were performed with
      four wavelengths of a Cd(114) lamp (644.0, 508.7, 480.1, and 467.9 nm) and at the
      temperature range of 19.6 degrees C-20.1 degrees C, the application is restricted
      when an He-Ne laser is used as the light source, which is mostly applied in
      optical precision measurement, and the environmental temperature is far away from
      20 degrees C as well. To solve this problem, a measurement system based on phase
      step interferometry for measuring the effect of the humidity to the RIA is
      presented, and a corresponding humidity correction equation is derived. The
      analysis and comparison results show that the uncertainty of the presented
      equation is better than that of Boensch and Potulski's. It is more suitable in
      present precision measurements by He-Ne laser, and the application temperature
      range extends to 14.6 degrees C-24.0 degrees C as well.

PMID- 25968029
TI  - Deconvolution method in designing freeform lens array for structured light
      illumination.
AB  - We have developed a deconvolution freeform lens array design approach to generate
      high-contrast structured light illumination patterns. This method constructs the
      freeform lens array according to the point response obtained by deconvoluting the
      prescribed illumination pattern with the blur response of the extended light
      source. This design method is more effective in designing a freeform lens array
      to achieve accurate structured light patterns. For a sinusoidal fringe pattern,
      the contrast ratio can be as high as 97%, compared to 62% achieved by the
      conventional ray mapping method. 

PMID- 25968030
TI  - Single-wavelength coarse phasing in segmented telescopes.
AB  - Space observations of fainter and more distant astronomical objects constantly
      require telescope primary mirrors with larger sizes. The diameters of monolithic
      primary mirrors are restricted to 10 m because of manufacturing limitations. For
      space telescopes, the primary mirrors are limited to less than 5 m due to fairing
      capacity. Segmented primary mirrors thus constitute an alternative solution to
      deal with the steady increase of primary mirror size. The optical path difference
      between the individual segments must be close to 0 (a few nanometers) in order to
      be diffraction-limited. In this paper, we propose a new intersegment piston
      sensor based on the coherence measurement of a star image. This sensor is
      intended to be used in the co-phasing system of future segmented mirrors.

PMID- 25968031
TI  - Image processing for cameras with fiber bundle image relay.
AB  - Some high-performance imaging systems generate a curved focal surface and so are
      incompatible with focal plane arrays fabricated by conventional silicon
      processing. One example is a monocentric lens, which forms a wide field-of-view
      high-resolution spherical image with a radius equal to the focal length. Optical
      fiber bundles have been used to couple between this focal surface and planar
      image sensors. However, such fiber-coupled imaging systems suffer from artifacts
      due to image sampling and incoherent light transfer by the fiber bundle as well
      as resampling by the focal plane, resulting in a fixed obscuration pattern. Here,
      we describe digital image processing techniques to improve image quality in a
      compact 126 degrees  field-of-view, 30 megapixel panoramic imager, where a 12 mm
      focal length F/1.35 lens made of concentric glass surfaces forms a spherical
      image surface, which is fiber-coupled to six discrete CMOS focal planes. We
      characterize the locally space-variant system impulse response at various stages:
      monocentric lens image formation onto the 2.5 MUm pitch fiber bundle, image
      transfer by the fiber bundle, and sensing by a 1.75 MUm pitch backside
      illuminated color focal plane. We demonstrate methods to mitigate moire artifacts
      and local obscuration, correct for sphere to plane mapping distortion and
      vignetting, and stitch together the image data from discrete sensors into a
      single panorama. We compare processed images from the prototype to those taken
      with a 10* larger commercial camera with comparable field-of-view and light
      collection.

PMID- 25968032
TI  - Spectral and spatial characterization of perfluorinated graded-index polymer
      optical fibers for the distribution of optical wireless communication cells.
AB  - In this paper, the characterization of a perfluorinated graded-index polymer
      optical fiber (PF-GIPOF) for a high-bitrate indoor optical wireless system is
      reported. PF-GIPOF is used here to interconnect different optical wireless access
      points that distribute optical free-space high-bitrate wireless communication
      cells. The PF-GIPOF channel is first studied in terms of transmission attenuation
      and frequency response and, in a second step, the spatial power profile
      distribution at the fiber output is analyzed. Both characterizations are
      performed under varying restricted mode launch conditions, enabling us to assess
      the transmission channel performance subject to potential connectorization errors
      within an environment where the end users may intervene by themselves on the home
      network infrastructure. 

PMID- 25968033
TI  - Measurement of grating visibility of a fiber Bragg grating based on bent-spectral
      analysis.
AB  - In this study, a technique for measuring the grating visibility of the fiber
      Bragg grating (FBG) based on bent-spectral analysis is proposed. From varying ac
      and dc coupling coefficients at different bending radii, the grating visibility
      is estimated with the aid of a simple mathematical model. The investigation
      begins with the estimation of the grating visibility from the transmission
      spectra of the FBG during the inscription process. After that, the FBGs are
      subjected to a bending test with reducing radii, and again the transmission
      spectra are recorded. It is shown that the estimated grating visibility is in
      agreement with the result determined from the earlier inscription process. 

PMID- 25968034
TI  - Subhertz linewidth laser by locking to a fiber delay line.
AB  - An ultralow-noise, subhertz 1.55 MUm erbium-doped fiber laser that is locked on
      an all-fiber-based Michelson interferometer is presented in this paper. The
      interferometer uses 500 m SMF-28 optical fiber and an acousto-optic modulator to
      allow heterodyne detection. By comparing two identical laser systems, a 0.67
      (0.21) Hz linewidth beat-note signal is achieved and we obtain fractional
      frequency instability of 7*10(-15) at short timescales (0.1-1 s). The frequency
      noise power spectral density of two identical lasers is below -1  dB Hz(2)/Hz at
      1 Hz and it reaches -18  dB Hz(2)/Hz from 200 Hz to 1 kHz.

PMID- 25968035
TI  - Flashlamp-pumped nanoparticle dispersion laser.
AB  - A flashlamp-pumped nanoparticle dispersion laser was demonstrated for the first
      time. The nanoparticles were Nd(2)O(3) modified with dimethyldichlorosilane
      (DMDCS) and dispersed in dimethyl sulfoxide-d(6) (DMSO-d(6)). The nanoparticle
      dispersion was pumped using four flashlamps to yield energy of 4.3 J in a 200 MUs
      pulse, at a wavelength of 1057 nm.

PMID- 25968036
TI  - Nanofocusing on circularly distributed tapered metallic waveguides by means of
      plasmonic vortex lenses.
AB  - We report our experimental results on the nanofocusing effect at the apex of
      planar nanotips placed at the center of a plasmonic vortex lens (PVL). PVLs are
      helical gratings that are able to generate surface plasmon polaritons (SPPs)
      carrying orbital angular momentum. A specific design allows us to couple the PVL
      with nanostructures placed at its center. The proposed configuration allows a
      simultaneous nanofocusing effect on four facing planar nanotips, showing
      efficient condensation of SPPs at the metal-air interface toward the end point of
      the tips. An optimized fabrication process allows us to prepare high-quality
      structures with a sharp tip apex. Near-field scanning optical microscopy has been
      used to demonstrate the nanofocusing effect. 

PMID- 25968037
TI  - Compensating for velocity truncation during subaperture polishing by controllable
      and time-variant tool influence functions.
AB  - The velocity-varying regime used in deterministic subaperture polishing employs a
      time-invariant tool influence function (TIF) to figure localized surface errors
      by varying the transverse velocities of polishing tools. Desired transverse
      velocities have to be truncated if they exceed the maximal velocity of computer
      numerical control (CNC) machines, which induces excessive material removal and
      reduces figuring efficiency (FE). A time-variant (TV) TIF regime is presented, in
      which a TIF serves as a variable to compensate for excessive material removal
      when the transverse velocities are truncated. Compared with other methods, the TV
      TIF regime exhibits better performance in terms of convergence rate, FE, and
      versatility; its operability can also be strengthened by a TIF library.
      Comparative experiments were conducted on a magnetorheological finishing machine
      to validate the effectiveness of the TV-TIF regime. Without a TV-TIF, the tool
      made an unwished dent (depth of 76 nm) at the center because of the velocity
      truncation problem. Through compensation with a TV-TIF, the dent was completely
      removed by the second figuring process, and a TV-TIF improved the FE from 0.029
      to 0.066  mm(3)/h.

PMID- 25968038
TI  - Surface identification from multiband LADAR reflectance with varied incidence
      angle via database mapping.
AB  - Incident angle dependencies of LADAR reflection depend on bulk material
      reflectivity and surface texture properties that can be exploited for surface
      identification. In this paper, surface identification via multiband LADAR
      reflected radiance is assessed using the nonconventional exploitation factors
      data system database. A statistics-based dimension reduction algorithm,
      stochastic neighborhood embedding (t-SNE), is used to separate the data clouds
      resulting from the monostatic LADAR reflected radiance and corresponding band
      ratios. The application of t-SNE to multiband reflected radiance effectively
      separates the data clouds, making surface identification via multiband LADAR
      reflectance possible in the presence of unknown incident angle dependencies and
      uncertainties. It is demonstrated that, for both the multiband monostatic
      reflected radiance and band ratios, the application of t-SNE mapping yields a
      significant improvement in surface identification from measurements with unknown
      or varied incident angles. 

PMID- 25968039
TI  - Distributed strain measurement based on long-gauge FBG and delayed
      transmission/reflection ratiometric reflectometry for dynamic structural
      deformation monitoring.
AB  - In this paper, we propose a delayed transmission/reflection ratiometric
      reflectometry (DTR(3)) scheme using a long-gauge fiber Bragg grating (FBG), which
      can be used for dynamic structural deformation monitoring of structures of
      between a few to tens of meters in length, such as airplane wings and helicopter
      blades. FBG sensors used for multipoint sensing generally employ wavelength
      division multiplexing techniques utilizing several Bragg central wavelengths; by
      contrast, the DTR(3) interrogator uses a continuous pulse array based on a
      pseudorandom number code and a long-gauge FBG utilizing a single Bragg wavelength
      and composed of simple hardware devices. The DTR(3) scheme can detect distributed
      strain at a 50 cm spatial resolution using a long-gauge FBG with a 100 Hz
      sampling rate. We evaluated the strain sensing characteristics of the long-gauge
      FBG when attached to a 2.5 m aluminum bar and a 5.5 m helicopter blade model,
      determining these structure natural frequencies in free vibration tests and their
      distributed strain characteristics in static tests.

PMID- 25968040
TI  - Er(3)/Yb(3)-codoped phosphate glass for short-length high-gain fiber lasers and
      amplifiers.
AB  - Er(3)/Yb(3)-codoped phosphate glass with compositions of (78.2-x)P(2)O(5)
      14Al(2)O(3)-5Li(2)O-1K(2)O-1.8Yb(2)O(3)-xEr(2)O(3)(x=0.2,0.4,0.6) in mol. % were
      investigated. Judd-Ofelt (JO) intensity parameters have been calculated to
      predict radiative properties based on absorption spectra. The stimulated emission
      cross section (sigma(e)) calculated according to McCumber theory was 1.50*10(-20)
      cm(2), almost twice larger than values reported before. The effective line width
      (Delta(eff)), full width at half-maximum (FWHM) and the quality parameters for
      designing optical amplifier devices were listed in the table compared with other
      types of phosphate glass matrices. A theoretical model of a Er(3)/Yb(3)-codoped
      system based on rate and power propagation equations was put forward to
      investigate the potential advantages of the materials applied for short-length,
      high-gain fiber amplifiers. A simulated gain of 32.2 and 2.6  dB/cm per unit
      length was achieved in 12.5-cm-long fiber.

PMID- 25968041
TI  - Nanostructured graphene-based hyperbolic metamaterial performing as a wide-angle
      near infrared electro-optical switch.
AB  - We propose a nanostructured hyperbolic metamaterial (HMM) that can make the
      transition between elliptic and hyperbolic regimes in the near infrared (IR)
      frequency range. This switchable HMM is a slab made of a periodic stack of
      metal/Al(2)O(3)/graphene/Al(2)O(3)/metal nano-layers. By tuning the graphene
      conductivity via tuning its chemical potential, through a variable external bias,
      the response of this highly anisotropic medium to a monochromatic TM incident
      light can be switched between a positive/negative refraction regime and a
      negative refraction/no-transmission regime. The proposed structure is suitable
      for applications such as beam splitters, modulators, four-port devices, and
      optical gates.

PMID- 25968042
TI  - N-single-helix photonic-metamaterial based broadband optical range circular
      polarizer by induced phase lags between helices.
AB  - In this work, we have designed a photonic-metamaterial based broadband circular
      polarizer using N=4 phase-lagged aluminum single helices arranged in a square
      array as a unit cell. The effect of phase differences between the helices in an
      array on the optical performance of the structure is studied, and a comparative
      study is done with that of multi-intertwined helices. It is observed that the
      proposed metamaterial structure shows circular polarization sensitivity over a
      broad optical wavelength range (~450-900  nm), with improved optical performance
      in average extinction ratio and broad positive circular dichroism in comparison
      to multiple intertwined helices. The induced phase lag between the helices in a
      square-array based unit cell reduces the linear birefringence and leads to the
      recovery of circular space symmetry in the structure. 

PMID- 25968044
TI  - Calling all interesting engineering techniques and laboratory notes: editorial.

PMID- 25968043
TI  - Simultaneous high-speed gas property measurements at the exhaust gas
      recirculation cooler exit and at the turbocharger inlet of a multicylinder diesel
      engine using diode-laser-absorption spectroscopy.
AB  - A diode-laser-absorption-spectroscopy-based sensor system was used to perform
      high-speed (100 Hz to 5 kHz) measurements of gas properties (temperature,
      pressure, and H(2)O vapor concentration) at the turbocharger inlet and at the
      exhaust gas recirculation (EGR) cooler exit of a diesel engine. An earlier
      version of this system was previously used for high-speed measurements of gas
      temperature and H(2)O vapor concentration in the intake manifold of the diesel
      engine. A 1387.2 N m tunable distributed feedback diode laser was used to scan
      across multiple H(2)O absorption transitions, and the direct absorption signal
      was recorded using a high-speed data acquisition system. Compact optical
      connectors were designed to conduct simultaneous measurements in the intake
      manifold, the EGR cooler exit, and the turbocharger inlet of the engine. For
      measurements at the turbocharger inlet, these custom optical connectors survived
      gas temperatures as high as 800 K using a simple and passive arrangement in which
      the temperature-sensitive components were protected from high temperatures using
      ceramic insulators. This arrangement reduced system cost and complexity by
      eliminating the need for any active water or oil cooling. Diode-laser
      measurements performed during steady-state engine operation were within 5% of the
      thermocouple and pressure sensor measurements, and within 10% of the H(2)O
      concentration values derived from the CO(2) gas analyzer measurements.
      Measurements were also performed in the engine during transient events. In one
      such transient event, where a step change in fueling was introduced, the diode
      laser sensor was able to capture the 30 ms change in the gas properties; the
      thermocouple, on the other hand, required 7.4 s to accurately reflect the change
      in gas conditions, while the gas analyzer required nearly 600 ms. To the best of
      our knowledge, this is the first implementation of such a simple and passive
      arrangement of high-temperature optical connectors as well as the first
      documented application of diode-laser absorption for high-speed gas dynamics
      measurements in the turbocharger inlet and EGR cooler exit of a diesel engine.

PMID- 25968045
TI  - Causal relationships between milk quality and coagulation properties in Italian
      Holstein-Friesian dairy cattle.
AB  - BACKGROUND: Recently, selection for milk technological traits was initiated in
      the Italian dairy cattle industry based on direct measures of milk coagulation
      properties (MCP) such as rennet coagulation time (RCT) and curd firmness 30 min
      after rennet addition (a30) and on some traditional milk quality traits that are
      used as predictors, such as somatic cell score (SCS) and casein percentage (CAS).
      The aim of this study was to shed light on the causal relationships between
      traditional milk quality traits and MCP. Different structural equation models
      that included causal effects of SCS and CAS on RCT and a30 and of RCT on a30 were
      implemented in a Bayesian framework. RESULTS: Our results indicate a non-zero
      magnitude of the causal relationships between the traits studied. Causal effects
      of SCS and CAS on RCT and a30 were observed, which suggests that the relationship
      between milk coagulation ability and traditional milk quality traits depends more
      on phenotypic causal pathways than directly on common genetic influence. While
      RCT does not seem to be largely controlled by SCS and CAS, some of the variation
      in a30 depends on the phenotypes of these traits. However, a30 depends heavily on
      coagulation time. Our results also indicate that, when direct effects of SCS, CAS
      and RCT are considered simultaneously, most of the overall genetic variability of
      a30 is mediated by other traits. CONCLUSIONS: This study suggests that selection
      for RCT and a30 should not be performed on correlated traits such as SCS or CAS
      but on direct measures because the ability of milk to coagulate is improved
      through the causal effect that the former play on the latter, rather than from a
      common source of genetic variation. Breaking the causal link (e.g. standardizing
      SCS or CAS before the milk is processed into cheese) would reduce the impact of
      the improvement due to selective breeding. Since a30 depends heavily on RCT, the
      relative emphasis that is put on this trait should be reconsidered and weighted
      for the fact that the pure measure of a30 almost double-counts RCT.

PMID- 25968046
TI  - CT textural analysis of hepatic metastatic colorectal cancer: pre-treatment tumor
      heterogeneity correlates with pathology and clinical outcomes.
AB  - PURPOSE: The purpose of the study was to determine if CT texture features of
      untreated hepatic metastatic colorectal cancer (CRC) relate to pathologic
      features and clinical outcomes. METHODS: Tumor texture analysis was performed on
      single hepatic metastatic lesions on pre-treatment contrast-enhanced CT scans in
      77 pts (mean age 58, 34F/43M) using a novel tool. Measures of heterogeneity,
      including entropy, kurtosis, skewness, mean, mean positive pixels (MPP), and
      standard deviation (SD) of pixel distribution histogram were derived with filter
      values corresponding to fine (spatial scaling factor (ssf) 2), medium (ssf 3, 4),
      and coarse textures (ssf 5, 6). Texture parameters were correlated with tumor
      grade, baseline serum CEA, and KRAS mutation status. Overall survival was also
      correlated using Cox proportional hazards models. Single-slice 2D vs. whole-tumor
      volumetric 3D texture analysis was compared in a subcohort of 20 patients.
      RESULTS: Entropy, MPP, and SD at medium filtration levels were significantly
      associated with tumor grade (MPP ssf 3 P = 0.002, SD ssf 3 P = 0.004, entropy ssf
      4 P = 0.007). Skewness was negatively associated KRAS mutation (P = 0.02).
      Entropy at coarse filtration levels was associated with survival (Hazard ratio
      (HR) for death 0.65, 95% CI 0.44-0.95, P = 0.03). Texture results for 2D and 3D
      analysis were similar. CONCLUSIONS: CT texture features, particularly entropy,
      MPP, and SD, are significantly associated with tumor grade in untreated CRC liver
      metastases. Tumor entropy at coarse filters correlates with overall survival.
      Single-slice 2D texture analysis appears to be adequate.

PMID- 25968048
TI  - Ectopic osteogenic tissue formation by MC3T3-E1 cell-laden
      chitosan/hydroxyapatite composite scaffold.
AB  - This study evaluates the suitability of a macroporous three-dimensional
      chitosan/hydroxyapatite (CS/HA) composite as a bone tissue engineering scaffold
      using MC3T3-E1 cells. The CS/HA scaffold was produced by freeze-drying, and
      characterized by means of SEM and FTIR. In vitro findings demonstrated that CS/HA
      supported attachment and proliferation of cells, and stimulated extracellular
      matrix (ECM) production. Tissue biocompatibility and osteogenic capacity of the
      cell-laden constructs were evaluated in an ectopic Wistar rat model. In vivo
      results showed that the MC3T3-E1 cell-laden CS/HA was essentially
      histocompatible, promoted neovascularization and calcified matrix formation, and
      secreted osteoblast-specific protein. We conclude that the composite scaffold
      evaluated has potential for applications in bone regeneration. 

PMID- 25968049
TI  - Study on how nanosilver-based inorganic antibacterial agent functions on biofilm
      formation of Candida albicans, inside the oral cavity.
AB  - BACKGROUND: Candida albicans is a common symbiotic fungus in the oral cavity,
      which can easily adhere to the surface of implanted materials. Highlighted by a
      broad antibacterial spectrum and potent antibacterial effects, nanosilver-based
      inorganic antibacterial agents (NSBIAA) are currently being hotly discussed with
      regard to their influences on biofilm formation of Candida albicans. PURPOSE:
      This paper aims to explore the influence of NSBIAA on biofilm formation of
      Candida albicans. METHOD: The XTT reduction method and the method of crystal
      violet determination were applied in measuring the influence of NSBIAA on biofilm
      formation of Candida albicans. In addition, biofilm morphology was determined by
      crystal violet staining. RESULT: It was observed that with the application of
      liquid antibacterial agent, at a concentration of 0.62 mg/ml, the biofilm
      activity of Candida albicans reduced (96.1 +/- 3.0) %, along with a reduction in
      the biomass (95.4 +/- 2.7) %, and biofilm formation was not observed under an
      inverted microscope. CONCLUSION: NSBIAA are able to inhibit biofilm formation.

PMID- 25968047
TI  - Safety of octreotide in hospitalized infants.
AB  - BACKGROUND: Octreotide is used off-label in infants for treatment of chylothorax,
      congenital hyperinsulinism, and gastrointestinal bleeding. The safety profile of
      octreotide in hospitalized infants has not been described; we sought to fill this
      information gap. METHODS: We identified all infants exposed to at least 1 dose of
      octreotide from a cohort of 887,855 infants discharged from 333 neonatal
      intensive care units managed by the Pediatrix Medical Group between 1997 and
      2012. We collected laboratory and clinical information while infants were exposed
      to octreotide and described the frequency of baseline diagnoses, laboratory
      abnormalities, and clinical adverse events (AEs). RESULTS: A total of 428 infants
      received 490 courses of octreotide. The diagnoses most commonly associated with
      octreotide use were chylothorax (50%), pleural effusion (32%), and hypoglycemia
      (22%). The most common laboratory AEs that occurred during exposure to octreotide
      were thrombocytopenia (47/1000 infant-days), hyperkalemia (21/1000 infant-days),
      and leukocytosis (20/1000 infant-days). Hyperglycemia occurred in 1/1000 infant
      days and hypoglycemia in 3/1000 infant-days. Hypotension requiring pressors (12%)
      was the most common clinical AE that occurred during exposure to octreotide.
      Necrotizing enterocolitis was observed in 9/490 (2%) courses, and death occurred
      in 11 (3%) infants during octreotide administration. CONCLUSION: Relatively few
      AEs occurred during off-label use of octreotide in this cohort of infants.
      Additional studies are needed to further evaluate the safety, dosing, and
      efficacy of this medication in infants.

PMID- 25968050
TI  - Efficient treatment of breast cancer xenografts with multifunctionalized iron
      oxide nanoparticles combining magnetic hyperthermia and anti-cancer drug
      delivery.
AB  - INTRODUCTION: Tumor cells can effectively be killed by heat, e.g. by using
      magnetic hyperthermia. The main challenge in the field, however, is the
      generation of therapeutic temperatures selectively in the whole tumor region. We
      aimed to improve magnetic hyperthermia of breast cancer by using innovative
      nanoparticles which display a high heating potential and are functionalized with
      a cell internalization and a chemotherapeutic agent to increase cell death.
      METHODS: The superparamagnetic iron oxide nanoparticles (MF66) were
      electrostatically functionalized with either Nucant multivalent pseudopeptide
      (N6L; MF66-N6L), doxorubicin (DOX; MF66-DOX) or both (MF66-N6LDOX). Their
      cytotoxic potential was assessed in a breast adenocarcinoma cell line MDA-MB-231.
      Therapeutic efficacy was analyzed on subcutaneous MDA-MB-231 tumor bearing female
      athymic nude mice. RESULTS: All nanoparticle variants showed an excellent heating
      potential around 500 W/g Fe in the alternating magnetic field (AMF, conditions:
      H=15.4 kA/m, f=435 kHz). We could show a gradual inter- and intracellular release
      of the ligands, and nanoparticle uptake in cells was increased by the N6L
      functionalization. MF66-DOX and MF66-N6LDOX in combination with hyperthermia were
      more cytotoxic to breast cancer cells than the respective free ligands. We
      observed a substantial tumor growth inhibition (to 40% of the initial tumor
      volume, complete tumor regression in many cases) after intratumoral injection of
      the nanoparticles in vivo. The proliferative activity of the remaining tumor
      tissue was distinctly reduced. CONCLUSION: The therapeutic effects of breast
      cancer magnetic hyperthermia could be strongly enhanced by the combination of
      MF66 functionalized with N6L and DOX and magnetic hyperthermia. Our approach
      combines two ways of tumor cell killing (magnetic hyperthermia and chemotherapy)
      and represents a straightforward strategy for translation into the clinical
      practice when injecting nanoparticles intratumorally.

PMID- 25968052
TI  - Remarkable effect of chalcogen substitution on an enzyme mimetic for deiodination
      of thyroid hormones.
AB  - Iodothyronine deiodinases are selenoenzymes which regulate the thyroid hormone
      homeostasis by catalyzing the regioselective deiodination of thyroxine (T4).
      Synthetic deiodinase mimetics are important not only to understand the mechanism
      of enzyme catalysis, but also to develop therapeutic agents as abnormal thyroid
      hormone levels have implications in different diseases, such as hypoxia,
      myocardial infarction, critical illness, neuronal ischemia, tissue injury, and
      cancer. Described herein is that the replacement of sulfur/selenium atoms in a
      series of deiodinase mimetics by tellurium remarkably alters the reactivity as
      well as regioselectivity toward T4. The tellurium compounds reported in this
      paper represent the first examples of deiodinase mimetics which mediate
      sequential deiodination of T4 to produce all the hormone derivatives including T0
      under physiologically relevant conditions. 

PMID- 25968051
TI  - Profiles of Connectedness: Processes of Resilience and Growth in Children With
      Cancer.
AB  - OBJECTIVE: Identified patterns of connectedness in youth with cancer and
      demographically similar healthy peers. METHOD: Participants included 153 youth
      with a history of cancer and 101 youth without a history of serious illness (8-19
      years). Children completed measures of connectedness, posttraumatic stress
      symptoms (PTSS), and benefit-finding. Parents also reported on children's PTSS.
      RESULTS: Latent profile analysis revealed four profiles: high connectedness
      (45%), low connectedness (6%), connectedness primarily to parents (40%), and
      connectedness primarily to peers (9%). These profiles did not differ by history
      of cancer. However, profiles differed on PTSS and benefit-finding. Children
      highly connected across domains displayed the lowest PTSS and highest benefit
      finding, while those with the lowest connectedness had the highest PTSS, with
      moderate PTSS and benefit-finding for the parent and peer profiles. CONCLUSION:
      Children with cancer demonstrate patterns of connectedness similar to their
      healthy peers. Findings support connectedness as a possible mechanism
      facilitating resilience and growth.

PMID- 25968053
TI  - The First Introduction of Graphene to Rechargeable Li-CO2 Batteries.
AB  - The utilization of the greenhouse gas CO2 in energy-storage systems is highly
      desirable. It is now shown that the introduction of graphene as a cathode
      material significantly improves the performance of Li-CO2 batteries. Such
      batteries display a superior discharge capacity and enhanced cycle stability.
      Therefore, graphene can act as an efficient cathode in Li-CO2 batteries, and it
      provides a novel approach for simultaneously capturing CO2 and storing energy. 

PMID- 25968055
TI  - Obstructive sleep apnoea should be deemed a cardiovascular disease.

PMID- 25968054
TI  - Reinforcement of STAT3 activity reprogrammes human embryonic stem cells to naive
      like pluripotency.
AB  - Leukemia inhibitory factor (LIF)/STAT3 signalling is a hallmark of naive
      pluripotency in rodent pluripotent stem cells (PSCs), whereas fibroblast growth
      factor (FGF)-2 and activin/nodal signalling is required to sustain self-renewal
      of human PSCs in a condition referred to as the primed state. It is unknown why
      LIF/STAT3 signalling alone fails to sustain pluripotency in human PSCs. Here we
      show that the forced expression of the hormone-dependent STAT3-ER (ER, ligand
      binding domain of the human oestrogen receptor) in combination with 2i/LIF and
      tamoxifen allows human PSCs to escape from the primed state and enter a state
      characterized by the activation of STAT3 target genes and long-term self-renewal
      in FGF2- and feeder-free conditions. These cells acquire growth properties, a
      gene expression profile and an epigenetic landscape closer to those described in
      mouse naive PSCs. Together, these results show that temporarily increasing STAT3
      activity is sufficient to reprogramme human PSCs to naive-like pluripotent cells.

PMID- 25968057
TI  - Ventricular assist device: destination UK.

PMID- 25968056
TI  - Elevated plasma norepinephrine level and sick sinus syndrome in patients with
      lone atrial fibrillation.
AB  - OBJECTIVE: Plasma norepinephrine (NE) level can be a guide to mortality in
      patients with heart failure. This study aimed to evaluate the significance of
      plasma NE level compared with plasma natriuretic peptides (atrial natriuretic
      peptide (ANP) and brain natriuretic peptide (BNP)) levels in patients with atrial
      fibrillation (AF). METHODS: Included in this study were 137 consecutive patients
      referred for catheter ablation of lone AF (paroxysmal in 90 and persistent in 47
      patients). Blood samples for measurements of ANP, BNP and NE were drawn in the
      supine position before the procedure. RESULTS: ANP, BNP and NE levels were
      greater in patients with persistent AF than in patients with paroxysmal AF
      (median (25th-75th centile)=28 (18-49) vs 69 (36-106), p<0.0001; 28 (15-50) vs 94
      (39-156), p<0.0001; and 315 (223-502) vs 382 (299-517) pg/mL, p=0.04,
      respectively). NE level correlated weakly with ANP and BNP levels (r=0.28 and
      r=0.23, respectively, p<0.01 for both). BNP and NE levels differed between
      patients with and without recurrence of AF (55 (26-135) vs 35 (18-64), p=0.005
      and 431 (323-560) vs 302 (225-436) pg/mL, p<0.001, respectively). Of note, only
      NE level was significantly greater in patients with symptomatic sick sinus
      syndrome (SSS) (n=21) than in those without SSS (560 (466-632) vs 321 (242-437)
      pg/mL, p<0.0001). Logistic regression analysis showed NE level to be the only
      independent discriminator for SSS (OR 1.006, 95% CI 1.002 to 1.010, p=0.001).
      CONCLUSIONS: An increase in plasma NE level was observed in patients with AF and
      SSS. Although this implies a pathophysiological link between clinical
      manifestation of SSS and the autonomic nervous dysfunction, further studies are
      needed to clarify the mechanisms for this novel finding.

PMID- 25968058
TI  - Olfactory Function Assessment of Blind Subjects Using the Sniffin' Sticks Test.
AB  - OBJECTIVE: In recent years, a growing number of studies have focused on the
      olfactory abilities of blind individuals as well as their tactile and auditory
      senses. In this study, we aimed to investigate possible alterations in the sense
      of smell in early- and late-blind subjects as compared with sighted controls,
      using a Sniffin' Sticks test battery. STUDY DESIGN: Prospective clinical study.
      SETTING: Tertiary referral center. SUBJECTS AND METHODS: A total of 66 subjects
      were included in the study. The subjects were divided into 2 groups: blind
      subjects-who were then subgrouped as subjects with congenital blindness (n = 17)
      and those with acquired blindness (n = 16)-and sighted subjects (n = 33). We
      compared both congenitally and acquired blind subjects with sighted counterparts
      using the Sniffin' Sticks test for odor threshold, odor discrimination, odor
      identification, and total odor scores. RESULTS: The blind subjects were more
      successful than their sighted counterparts in odor discrimination and odor
      threshold tasks. There was no statistically significant difference between the
      blind participants and the sighted individuals in terms of odor identification
      value. Another important finding was that the difference between individuals with
      congenital blindness and those with acquired blindness was not significant in any
      of the parameters. CONCLUSION: This finding may suggest that odor discrimination
      and odor threshold in blind people were superior to those of controls. There was
      no difference in any of the results of tasks among congenital and acquired blind
      subjects.

PMID- 25968059
TI  - Revision Transcervical Medialization Laryngoplasty for Unilateral Vocal Fold
      Paralysis.
AB  - OBJECTIVE: To identify patterns of failure following transcervical medialization
      laryngoplasty for unilateral vocal fold paralysis and describe indications and
      revision techniques for optimal vocal outcomes. STUDY DESIGN: Case series with
      chart review. SETTING: Tertiary care center. SUBJECTS AND METHODS: Thirty-nine
      consecutive patients between January 2005 and April 2014 undergoing transcervical
      revision of failed primary medialization laryngoplasty were identified.
      Demographics, etiology, stroboscopic assessment, and surgical techniques were
      recorded. Patient self-assessment using the Voice-Related Quality-of-Life (VRQOL)
      questionnaire and objective acoustic and aerodynamic assessments performed pre-
      and postoperatively were analyzed using t tests for paired comparisons. RESULTS:
      Thirty-nine patients underwent 48 transcervical revision surgeries. Median follow
      up was 14.6 months from time of final revision surgery. Indications included
      anterior glottic incompetence (38/48, 79%), posterior glottic incompetence
      (20/48, 42%), glottic overclosure (8/48, 17%), and/or decreased phonatory
      pliability (12/48, 25%). A combination of findings was present in 21 (44%)
      surgeries. Revision techniques included either anterior augmentation,
      arytenopexy, and cricothyroid subluxation (alone or in combination) in 46 of 48
      (96%) patients or partial implant removal alone in 2 patients. Seven patients
      (18%) required multiple revisions. A complete set of voice parameters was
      available for 22 patients, and statistically significant improvements included
      VRQOL scores, fundamental frequency in females, jitter, noise-to-harmonic ratio,
      and mean airflow rate. CONCLUSION: Patterns of failure in patients with
      suboptimal phonatory function after transcervical medialization laryngoplasty
      included persistent glottic incompetence, glottic overclosure, and decreased
      vocal fold pliability. Revision transcervical medialization surgery, guided by
      individualized consideration of vocal fold position and surface pliability, can
      improve phonatory outcomes.

PMID- 25968060
TI  - Nerve Growth Factor Signals as Possible Pathogenic Biomarkers for Perineural
      Invasion in Adenoid Cystic Carcinoma.
AB  - OBJECTIVE: The molecular mechanisms underlying perineural invasion (PNI)-a
      characteristic pathological feature of adenoid cystic carcinoma (ACC)-remain
      largely unclear. Recently, nerve growth factor (NGF) has been implicated in
      perineural invasion in certain malignancies. Overexpression of Myb related to the
      MYB-NFIB fusion gene in ACC has also been correlated with perineural invasion and
      survival. However, this concept is controversial. The aim of this study was to
      examine the expression of NGF together with its receptors, tropomyosin receptor
      kinase A (TrkA) and p75NRT, and Myb in ACC and assess their relationship with
      perineural invasion and survival. STUDY DESIGN: Case series with chart review.
      SETTING: The University of Tokyo Hospital. SUBJECTS AND METHODS: We
      retrospectively analyzed 37 patients with ACC surgically treated from 1991 to
      2011. We examined expression levels of NGF, TrkA, p75NRT, and Myb in the ACC
      specimens and their correlations with PNI and prognosis. RESULTS: NGF, TrkA,
      p75NRT, and Myb overexpression rates were 65%, 65%, 30%, and 62%, respectively.
      Pearson product-moment correlation coefficient revealed a strong correlation
      between NGF/TrkA immunostaining and PNI (NGF: r = 0.68, P < .0001; TrkA: r =
      0.53, P = .0007). Moreover, NGF overexpression was significantly associated with
      worse 8-year local control rate (27% vs 80%, P = .005). However, p75NRT and Myb
      expression was related to neither perineural invasion nor survival. CONCLUSION:
      Our findings demonstrated that NGF and TrkA overexpression, but not Myb and
      p75NRT overexpression, may contribute to PNI and thus cause local recurrence in
      patients with ACC.

PMID- 25968061
TI  - Vestibular Dysfunction in Patients with Enlarged Vestibular Aqueduct.
AB  - OBJECTIVE: Enlarged vestibular aqueduct (EVA) is the most common inner ear
      malformation. While a strong correlative relationship between EVA and hearing
      loss is well established, its association with vestibular dysfunction is less
      well understood. In this study, we examine the effects of EVA on the vestibular
      system in patients with EVA. STUDY DESIGN: Prospective, cross-sectional study of
      a cohort ascertained between 1999 and 2013. SETTING: National Institutes of
      Health Clinical Center, a federal biomedical research facility. SUBJECTS AND
      METHODS: In total, 106 patients with unilateral or bilateral EVA, defined as a
      midpoint diameter greater than 1.5 mm, were referred or self-referred to
      participate in a study of the clinical and molecular aspects of EVA. Clinical
      history was ascertained with respect to the presence or absence of various
      vestibular signs and symptoms and history of head trauma. Videonystagmography
      (VNG), cervical vestibular evoked myogenic potential (cVEMP), and rotational
      vestibular testing (RVT) were performed to assess the vestibular function.
      RESULTS: Of the patients with EVA, 45% had vestibular signs and symptoms, and 44%
      of tested patients had abnormal VNG test results. An increased number of
      vestibular signs and symptoms was correlated with the presence of bilateral EVA
      (P = .008) and a history of head injury (P < .001). Abnormal VNG results also
      correlated with a history of head injury (P = .018). CONCLUSION: Vestibular
      dysfunction is common in patients with EVA. However, not all patients with
      vestibular signs and symptoms have abnormal vestibular test results. Clinicians
      should be aware of the high prevalence of vestibular dysfunction in patients with
      EVA.

PMID- 25968062
TI  - An Elongated Pituitary Stalk Resembling the Lining of a Dermoid Cyst during
      Endoscopic Endonasal Approach.

PMID- 25968063
TI  - A systematic review investigating the cumulative incidence of chronic kidney
      disease in young adults with impaired glucose tolerance.
AB  - BACKGROUND: It is known that risk of chronic kidney disease (CKD) is elevated in
      patients with diabetes mellitus but it is not clear whether the risk is also
      elevated with impaired glucose tolerance (IGT). If the risk is increased, it is
      not known if this is confined to people with IGT who progress to type 2 diabetes
      (T2DM). The purpose of this systematic review is to determine the relative risk
      of CKD in young adults (aged 18 to 40 years) with IGT (exposed group) compared to
      those without glycaemic abnormality (comparator group). METHODS/DESIGN: The
      following electronic databases will be systematically searched from inception to
      January 2015 for relevant studies: CINAHL, EMBASE, MEDLINE, PubMed, Cochrane
      libraries and grey literature. Two independent reviewers will screen search
      results, extract data, select studies for inclusion and assess their quality.
      Studies including young adults (aged 18 to 40 years) with IGT containing any of
      the following CKD markers will be included: estimated glomerular filtration rate
      (eGFR), albumin creatinine ratio (ACR), protein creatinine ratio (PCR), serum
      creatinine (SCr) and creatinine clearance (CrCl) levels. Studies at any time
      period after diagnosis of IGT and with any length of follow-up will be included.
      The proportion of IGT participants reporting each outcome will be documented.
      Relative risks (RR) and odds ratios (OR) will be extracted or calculated from raw
      data. If possible, study results will be combined in a meta-analysis. DISCUSSION:
      The results of this comprehensive review will establish the evidence for the
      association between IGT and the risk of developing CKD in young adults (aged 18
      to 40 years). SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014007081.

PMID- 25968064
TI  - First confirmation of Pseudogymnoascus destructans in British bats and
      hibernacula.
AB  - White-nose syndrome (WNS) is a fatal fungal infection of bats in North America
      caused by Pseudogymnoascus destructans. P. destructans has been confirmed in
      Continental Europe but not associated with mass mortality. Its presence in Great
      Britain was unknown. Opportunistic sampling of bats in GB began during the winter
      of 2009. Any dead bats or samples from live bats with visible fungal growths were
      submitted to the Animal Health and Veterinary Laboratories Agency for culture.
      Active surveillance by targeted environmental sampling of hibernacula was carried
      out during the winter of 2012/2013. Six hibernacula were selected by their
      proximity to Continental Europe. Five samples, a combination of surface swabs or
      sediment samples, were collected. These were sent to the Center for Microbial
      Genetics and Genomics, Northern Arizona University, for P. destructans PCR. Forty
      eight incidents were investigated between March 2009 and July 2013. They
      consisted of 46 bat carcases and 31 other samples. A suspected P. destructans
      isolate was cultured from a live Daubenton's bat (Myotis daubentonii) sampled in
      February 2013. This isolate was confirmed by the Mycology Reference Laboratory,
      Bristol (Public Health England), as P. destructans. A variety of fungi were
      isolated from the rest but all were considered to be saprophytic or incidental.
      P. destructans was also confirmed by the Center for Microbial Genetics and
      Genomics in five of the six sites surveyed. 

PMID- 25968065
TI  - TF-Test Modified: New Diagnostic Tool for Human Enteroparasitosis.
AB  - Intestinal parasitosis is highly prevalent worldwide, being among the main causes
      of illness and death in humans. Currently, laboratory diagnosis of the intestinal
      parasites is accomplished through manual technical procedures, mostly developed
      decades ago, which justifies the development of more sensitive and practical
      techniques. Therefore, the main objective of this study was to develop, evaluate,
      and validate a new parasitological technique referred to as TF-Test Modified, in
      comparison to three conventional parasitological techniques: TF-Test
      Conventional; Rugai, Mattos & Brisola; and Helm Test/Kato-Katz. For this
      realization, we collected stool samples from 457 volunteers located in endemic
      areas of Campinas, Sao Paulo, Brazil, and statistically compared the techniques.
      Intestinal protozoa and helminths were detected qualitatively in 42.23% (193/457)
      of the volunteers by TF-Test Modified technique, against 36.76% (168/457) by TF
      Test Conventional, 5.03% (23/457) by Helm Test/Kato-Katz, and 4.16% (19/457) by
      Rugai, Mattos & Brisola. Furthermore, the new technique presented "almost perfect
      kappa" agreement in all evaluated parameters with 95% (P < 0.05) of estimation.
      The current study showed that the TF-Test Modified technique can be
      comprehensively used in the diagnosis of intestinal protozoa and helminths, and
      its greater diagnostic sensitivity should help improving the quality of
      laboratory diagnosis, population surveys, and control of intestinal parasites. 

PMID- 25968066
TI  - In-service training for health professionals to improve care of seriously ill
      newborns and children in low-income countries.
AB  - BACKGROUND: A variety of in-service emergency care training courses are currently
      being promoted as a strategy to improve the quality of care provided to seriously
      ill newborns and children in low-income countries. Most courses have been
      developed in high-income countries. However, whether these courses improve the
      ability of health professionals to provide appropriate care in low-income
      countries remains unclear. This is the first update of the original review.
      OBJECTIVES: To assess the effects of in-service emergency care training on health
      professionals' treatment of seriously ill newborns and children in low-income
      countries. SEARCH METHODS: For this update, we searched the Cochrane Database of
      Systematic Reviews, part of The Cochrane Library (www.cochranelibrary.com);
      MEDLINE, Ovid SP; EMBASE, Ovid SP; the Cochrane Central Register of Controlled
      Trials (CENTRAL), part of The Cochrane Library (www.cochranelibrary.com)
      (including the Cochrane Effective Practice and Organisation of Care (EPOC) Group
      Specialised Register); Science Citation Index and Social Sciences Citation Index,
      Institute for Scientific Information (ISI) Web of Knowledge/Science and eight
      other databases. We performed database searches in February 2015. We also
      searched clinical trial registries, websites of relevant organisations and
      reference lists of related reviews. We applied no date, language or publication
      status restrictions when conducting the searches. SELECTION CRITERIA: Randomised
      trials, non-randomised trials, controlled before and after studies and
      interrupted-time-series studies that compared the effects of in-service emergency
      care training versus usual care were eligible for inclusion. We included only
      hospital-based studies and excluded community-based studies. Two review authors
      independently screened and selected studies for inclusion. DATA COLLECTION AND
      ANALYSIS: Two review authors independently extracted data and assessed study risk
      of bias and confidence in effect estimates (certainty of evidence) for each
      outcome using GRADE (Grades of Recommendation, Assessment, Development and
      Evaluation). We described results and presented them in GRADE tables. MAIN
      RESULTS: We identified no new studies in this update. Two randomised trials
      (which were included in the original review) met the review eligibility criteria.
      In the first trial, newborn resuscitation training compared with usual care
      improved provider performance of appropriate resuscitation (trained 66% vs usual
      care 27%, risk ratio 2.45, 95% confidence interval (CI) 1.75 to 3.42; moderate
      certainty evidence) and reduced inappropriate resuscitation (trained mean 0.53 vs
      usual care 0.92, mean difference 0.40, 95% CI 0.13 to 0.66; moderate certainty
      evidence). Effect on neonatal mortality was inconclusive (trained 28% vs usual
      care 25%, risk ratio 0.77, 95% CI 0.40 to 1.48; N = 27 deaths; low certainty
      evidence). Findings from the second trial suggest that essential newborn care
      training compared with usual care probably slightly improves delivery room
      newborn care practices (assessment of breathing, preparedness for resuscitation)
      (moderate certainty evidence). AUTHORS' CONCLUSIONS: In-service neonatal
      emergency care courses probably improve health professionals' treatment of
      seriously ill babies in the short term. Further multi-centre randomised trials
      evaluating the effects of in-service emergency care training on long-term
      outcomes (health professional practice and patient outcomes) are needed.

PMID- 25968067
TI  - MAPK inhibitors modulate Smad2/3/4 complex cyto-nuclear translocation in
      myofibroblasts via Imp7/8 mediation.
AB  - Mitogen-activated protein kinase (MAPK) pathway-dependent linker phosphorylation
      of Smad2/3 and subsequent formation of Smad2/3/4 complex and its nuclear
      translocation are crucial for dysregulated transforming growth factor beta (TGF)
      beta/Smad signaling in liver fibrosis. Abrogation of this critical step of TGF
      beta/Smad signaling leading to liver fibrosis could provide new insights for
      future therapy, but the mechanisms remain incompletely understood. In pursuit, we
      investigated the subcellular expression and nuclear trafficking of the rate
      limiting Smad2/3/4 complex in exogenous TGF-beta1-stimulated myofibroblasts
      (MFBs) using three MAPK-specific inhibitors. Our results showed that exogenous
      TGF-beta1 stimulation of MFBs produced both increased protein expression and
      nuclear translocation of phosphorylated (p)-Smad2C/L, oncogenic pSmad3L, Smad4,
      importin7/8 (Imp7/8), and plasminogen activator inhibitor (PAI)-1 (Protein and
      mRNA), while decreased Smad7 protein expression. However, the MAPK-specific
      inhibitors differentially reversed these observations; for instance, ERK-specific
      inhibitor blocked the expression and nuclear translocation of pSmad2C/L, while
      both JNK and p38-specific inhibitors blocked the expression and nuclear
      translocation of pSmad2C/L and oncogenic pSmad3L. The MAPK-specific inhibitors
      had no significant effect on the total protein expression of Smad4, but rather
      significantly blocked its nuclear translocation. All the MAPK-specific inhibitors
      restored Smad7 expression and also decreased Imp7/8 and PAI-1 (Protein and mRNA)
      expression. Evidently, the MAPK-specific inhibitors blocked Smad2/3/4 complex
      formation via restoration of inhibitory Smad7 expression and blockade of Smad3L
      phosphorylation, while they blocked nuclear translocation of Smad2/3/4 complex
      through inhibition of Imp7/8 leading to decreased PAI-1 (Protein and mRNA)
      expression. 

PMID- 25968068
TI  - Inhibitory effect of oblongifolin C on allergic inflammation through the
      suppression of mast cell activation.
AB  - Oblongifolin C (OC), a natural small molecule compound extracted from Garcinia
      yunnanensis Hu, has been previously shown to have anti-cancer effect, but the
      anti-allergic effect of OC has not yet been investigated. The aim of the present
      study is to determine the anti-allergic effect of OC on IgE/Ag-induced mouse bone
      marrow-derived mast cells (BMMCs) and on the passive systemic anaphylaxis (PSA)
      reaction in mice. OC clearly suppressed cyclooxygenase-2 (COX-2)-dependent
      prostaglandin D2 (PGD2) generation as well as leukotriene C4 (LTC4) generation
      and the degranulation reaction in IgE/Ag-stimulated BMMCs. Biochemical analyses
      of the IgE/Ag-mediated signaling pathways showed that OC suppressed the
      phosphorylation of phospholipase Cgamma1 (PLCgamma1)-mediated intracellular
      Ca(2+) influx and the nuclear factor-kappaB (NF-kappaB) pathway, as well as the
      phosphorylation of mitogen-activated protein (MAP) kinases. Although OC did not
      inhibit the phosphorylation of Fyn, Lyn, and Syk, it directly inhibited the
      tyrosine kinase activity in vitro. Moreover, oral administration of OC inhibited
      the IgE-induced PSA reaction in a dose-dependent manner. Taken together, the
      present study provides new insights into the anti-allergic activity of OC, which
      could be a promising candidate for allergic therapy. 

PMID- 25968069
TI  - Flucelvax (Optaflu) for   seasonal influenza.
AB  - Conventional egg-based manufacturing technology for seasonal influenza vaccines
      has several drawbacks, including its inflexibility, reliance on egg supplies,
      risk of contamination, absence of growth of some isolates and egg-adaptive viral
      mutations that threaten vaccine matching. To overcome these limitations, cell
      culture-derived vaccines have been designed, including the trivalent inactivated
      vaccine Flucelvax(r)/Optaflu(r) (brand names in the US/EU, respectively).
      Flucelvax(r)/Optaflu(r) has gained wide regulatory approval and is currently
      implemented in several countries. Non-clinical studies have assuaged hypothetical
      concerns regarding oncogenicity and use in persons allergic to dogs. Ample
      clinical data suggest the non-inferiority of Flucelvax(r)/Optaflu(r) to egg-based
      vaccines in terms of immunogenicity, safety and tolerability, and it has
      fulfilled American and European mandatory requirements. Although
      Flucelvax(r)/Optaflu(r) is currently indicated only for adults and the elderly,
      pediatric data indicate its good immunogenicity and safety. This paper provides
      an update on the clinical development of Flucelvax(r)/Optaflu(r), its seasonal
      trials and available post-marketing surveillance data.

PMID- 25968070
TI  - Close teamwork between Nrf2 and peroxiredoxins 1 and 6 for the regulation of
      prostaglandin D2 and E2 production in macrophages in acute inflammation.
AB  - Inflammation is a complex biological self-defense reaction triggered by tissue
      damage or infection by pathogens. Acute inflammation is regulated by the time-
      and cell type-dependent production of cytokines and small signaling molecules
      including reactive oxygen species and prostaglandins. Recent studies have
      unveiled the important role of the transcription factor Nrf2 in the regulation of
      prostaglandin production through transcriptional regulation of peroxiredoxins 1
      and 6 (Prx1 and Prx6) and lipocalin-type prostaglandin D synthase (L-PGDS). Prx1
      and Prx6 are multifunctional proteins important for cell protection against
      oxidative stress, but also work together to facilitate production of
      prostaglandins E2 and D2 (PGE2 and PGD2). Prx1 secreted from cells under mild
      oxidative stress binds Toll-like receptor 4 and induces NF-kappaB activation,
      important for the expression of cyclooxygenase-2 and microsomal PGE synthase-1
      (mPGES-1) expression. The activated MAPKs p38 and ERK phosphorylate Prx6, leading
      to NADPH oxidase-2 activation, which contributes to production of PGD2 by
      hematopoietic prostaglandin D synthase (H-PGDS). PGD2 and its end product 15
      deoxy-?(12,14)-prostaglandin J2 (15d-PGJ2) activate Nrf2 thereby forming a
      positive feedback loop for further production of PGD2 by L-PGDS. Maintenance of
      cellular glutathione levels is an important role of Nrf2 not only for cell
      protection but also for the synthesis of prostaglandins, as mPGES-1 and H-PGDS
      require glutathione for their activities. This review is aimed at describing the
      functions of Prx1 and Prx6 in the regulation of PGD2 and PGE2 production in acute
      inflammation in macrophages and the importance of 15d-PGJ2 as an intrinsic Nrf2
      activator. 

PMID- 25968071
TI  - Spectrocolourimetry visualized differences in sexual skin colouration in
      macaques.
AB  - The females of some catarrhines develop conspicuous sexual skin transformations
      in their hind limbs. Among macaques (one of the radiated and adapted catarrhine
      groups with diversified sexual skin transformations), differences in sexual skin
      colouration between the Japanese macaque Macaca fuscata and the rhesus macaque M.
      mulatta have not been quantitatively analysed. In this study, the sexual skin
      colouration of these macaques was spectrocolourimetrically measured in the non
      mating season (NMS) and the mating season (MS) and represented in a CIELAB space
      with the variables L*, a* and b*. The variables L*, a* and b* represent positions
      on the light-dark, red/magenta-green, and yellow-blue axes, respectively. In the
      Japanese macaques the average +/- SD of L*, a* and b* was 53.61 +/- 3.31, 11.51
      +/- 4.57 and 6.66 +/- 2.25 in the NMS and 46.60 +/- 2.78, 19.97 +/- 2.99 and 8.80
      +/- 1.34 in the MS, respectively, while in the rhesus macaques the average +/- SD
      of L*, a* and b* was 60.09 +/- 3.96, 5.99 +/- 4.59 and 5.83 +/- 2.37 in the NMS
      and 52.70 +/- 6.54, 13.62 +/- 6.86 and 8.07 +/- 1.43 in the MS, respectively. The
      sexual skin of the Japanese macaques was consistently much redder (larger a*) and
      darker (smaller L*) than that of the rhesus macaques. The smaller L* suggested a
      greater dermal melanin content in the Japanese macaques. These closely related
      macaque species have similar but distinct sexual skin colourations.
      Spectrocolourimetry is thus useful to suggest the histophysiological background
      of the colouration.

PMID- 25968072
TI  - Oncologic Concerns regarding Laparoscopic Cytoreductive Surgery in Patients with
      Advanced Ovarian Cancer Submitted to Neoadjuvant Chemotherapy.
AB  - BACKGROUND: Presently, the use of laparoscopy in advanced ovarian cancer (AOC) is
      extremely controversial. In the era of neoadjuvant chemotherapy (NACT),
      endoscopic debulking surgery could be a reasonable alternative for selected
      patients with primarily unresectable disease. OBJECTIVES: To evaluate the
      feasibility as well as the operative and oncologic safety of laparoscopic
      debulking surgery in patients with AOC submitted to NACT. METHODS: This is a
      pilot observational study on initially unresectable, high-grade serous ovarian
      cancer treated with a sequence of 6 cycles of carboplatin and paclitaxel followed
      by debulking surgery performed by laparoscopy (group 1) or laparotomy (group 2).
      The inclusion criteria were clinical complete response, CA-125 normalization,
      imaging without disease in critical areas, and optimal cytoreduction. RESULTS:
      From January 2011 to March 2014, 21 patients were included. Ten women underwent
      laparoscopy and 11 laparotomy. No epidemiological or oncologic differences were
      observed between the groups. No surgery-related casualties, intraoperative
      complications, conversion to laparotomy, or excessive blood loss or transfusion
      was detected in the laparoscopic procedures. The mean time of operation was 292
      min. The length of hospital stay averaged 3.6 days. Two women in group 1
      developed relevant complications. After a mean follow-up of 20 months, the
      recurrence rates were similar, i.e. 80% in group 1 versus 88% in group 2.
      Although statistical significance was not reached, the mortality related to
      cancer was considerably higher (20 vs. 0%; p = 0.086) and the mean chemotherapy
      free interval was markedly shorter in group 1 (13.3 vs. 20.5 months; p = 0.288).
      CONCLUSION: Laparoscopic optimal debulking surgery after NACT is feasible and
      effective in selected patients. Nevertheless, laparoscopy was substantially
      associated with inferior oncologic results. Endoscopic cytoreduction in AOC
      should be cautiously suggested until larger prospective trials confirm the
      observed results.

PMID- 25968073
TI  - The potential effects of phytoplankton on the occurrence of organochlorine
      pesticides (OCPs) and polycyclic aromatic hydrocarbons (PAHs) in water from Lake
      Taihu, China.
AB  - Seasonal distribution of organochlorine pesticides (OCPs) and polycyclic aromatic
      hydrocarbons (PAHs) and their possible interactions with phytoplankton species in
      water from Lake Taihu were investigated. OCP concentrations ranged from 69.95 to
      223.08 ng L(-1) in winter and from 80.95 to 376.03 ng L(-1) in summer, while PAHs
      ranged from 45.40 to 232.74 ng L(-1) in winter and 49.53 to 197.72 ng L(-1) in
      summer. Such physicochemical and biological parameters as the larger amounts of
      pollutants taken up by phytoplankton, the increased atmospheric wet deposition,
      the discharge of wastewater, and the resuspension of polluted sediments in summer
      time were responsible for the higher residues of both OCPs and PAHs than in
      winter. Canonical correspondence analysis (CCA) between phytoplankton biomass and
      micropollutants indicated high affinity of OCPs to Bacillariophyta and
      Cryptophyta and PAHs to Cyanophyta and Chlorophyta, documenting the ecological
      effects of phytoplankton on the biogeochemical processes of OCPs and PAHs and
      thus should be further investigated especially in hyper-eutrophic lakes. 

PMID- 25968074
TI  - Is lymph node metastasis of canine grade 2 MCTs justification for adjuvant
      therapy?

PMID- 25968075
TI  - Letter to the editor.

PMID- 25968076
TI  - Sao Paulo Animal Cancer Registry, the first in Latin America.

PMID- 25968077
TI  - Design of a Competency Evaluation Model for Clinical Nursing Practicum, Based on
      Standardized Language Systems: Psychometric Validation Study.
AB  - PURPOSE: To develop an evaluation system of clinical competencies for the
      practicum of nursing students based on the Nursing Interventions Classification
      (NIC). DESIGN AND METHODS: Psychometric validation study: the first two phases
      addressed definition and content validation, and the third phase consisted of a
      cross-sectional study for analyzing reliability. The study population was
      undergraduate nursing students and clinical tutors. FINDINGS: Through the Delphi
      technique, 26 competencies and 91 interventions were isolated. Cronbach's alpha
      was 0.96. Factor analysis yielded 18 factors that explained 68.82% of the
      variance. Overall inter-item correlation was 0.26, and total-item correlation
      ranged between 0.66 and 0.19. CONCLUSIONS: A competency system for the nursing
      practicum, structured on the NIC, is a reliable method for assessing and
      evaluating clinical competencies. Further evaluations in other contexts are
      needed. CLINICAL RELEVANCE: The availability of standardized language systems in
      the nursing discipline supposes an ideal framework to develop the nursing
      curricula.

PMID- 25968079
TI  - Is leg pain a significant contributor to health care budget pain?

PMID- 25968078
TI  - Clinical Benefit of Gastric Staple Line Reinforcement (SLR) in Gastrointestinal
      Surgery: a Meta-analysis.
AB  - BACKGROUND: The objective of this study was to assess whether the use of staple
      line reinforcement (SLR) reduces staple line complications (SLC). Mechanical
      staple lines are essential for gastrointestinal surgery such as bariatric
      surgery. However, SLC, such as bleeding and leakage, still occur. The purposes of
      this study were to provide quantitative evidence on the relative efficacy of
      gastric SLR and to compare the rates of effectiveness of three commonly used
      methods. METHODS: A search of the medical literature in English language journals
      identified studies from Jan 1, 2000, to Dec 31, 2013, using the following
      reinforcement types: (1) no reinforcement, (2) oversewing, (3) a biocompatible
      glycolide copolymer, and (4) bovine pericardium after gastric bypasses and sleeve
      gastrectomies. Types of reinforcement were compared using a random-effects model.
      RESULTS: This meta-analysis reviewed 16,967 articles, extracting data on 56,309
      patients concerning leak and 41,864 patients concerning bleeding. Over 40 % of
      patients had no reinforcement, resulting in the highest leak rate (2.75 %) and
      bleed rate (3.45 %). Overall, reinforcing with bovine pericardium had the lowest
      leak (1.28 %) and bleed (1.23 %) rates. Suture oversewing was better than no
      reinforcement but not as effective as bovine pericardium for leak (2.45 %) and
      bleed (2.69 %) rates. Buttressing with a biocompatible glycolide copolymer
      resulted in the second highest leak rate (2.61 %) and a bleed rate of 2.48 % but
      had significantly lower bleed rates than no reinforcement. CONCLUSIONS: SLR
      provided superior results for patients compared to no reinforcement for reducing
      SLC. Buttressing with bovine pericardium resulted in the most favorable outcomes.
      The effectiveness of different methods used to reinforce the staple line in
      gastric surgery does not appear to be equal.

PMID- 25968083
TI  - [Therapy-resistant purulent papules and nodes on both buttocks and thighs].

PMID- 25968082
TI  - [Cutaneous Malassezia infections and Malassezia associated dermatoses: An
      update].
AB  - The lipophilic yeast fungus Malassezia (M.) spp. is the only fungal genus or
      species which is part of the physiological human microbiome. Today, at least 14
      different Malassezia species are known; most of them can only be identified using
      molecular biological techniques. As a facultative pathogenic microorganism,
      Malassezia represents the causative agent both of superficial cutaneous
      infections and of blood stream infections. Pityriasis versicolor is the probably
      most frequent infection caused by Malassezia. Less common, Malassezia
      folliculitis occurs. There is only an episodic report on Malassezia-induced
      onychomycosis. Seborrhoeic dermatitis represents a Malassezia-associated
      inflammatory dermatosis. In addition, Malassezia allergenes should be considered
      as the trigger of "Head-Neck"-type atopic dermatitis. Ketoconazole possesses the
      strongest in vitro activity against Malassezia, and represents the treatment of
      choice for topical therapy of pityriasis versicolor. Alternatives include other
      azole antifungals but also the allylamine terbinafine and the hydroxypyridone
      antifungal agent ciclopirox olamine. "Antiseborrhoeic" agents, e.g. zinc
      pyrithione, selenium disulfide, and salicylic acid, are also effective in
      pityriasis versicolor. The drug of choice for oral treatment of pityriasis
      versicolor is itraconazole; an effective alternative represents fluconazole.
      Seborrhoeic dermatitis is best treated with topical medication, including topical
      corticosteroids and antifungal agents like ketoconazole or sertaconazole.
      Calcineurin inhibitors, e.g. pimecrolimus and tacrolimus, are reliable in
      seborrhoeic dermatitis, however are used off-label. 

PMID- 25968084
TI  - Serum diamine oxidase activity as a predictor of gastrointestinal toxicity and
      malnutrition due to anticancer drugs.
AB  - BACKGROUND AND AIM: Objective evaluation of intestinal mucosal damage due to
      anticancer drugs is generally difficult. Serum diamine oxidase (DAO) activity is
      reported to reflect the integrity and maturity of the small intestinal mucosa.
      Therefore, we investigated whether serum DAO activity is an indicator of
      gastrointestinal toxicity or nutritional status in patients receiving
      chemotherapy. METHODS: We prospectively enrolled 20 patients with unresectable
      metastatic gastric cancer who received oral S-1 (80 mg/m(2) ) on days 1-14, and
      intravenous cisplatin (60 mg/m(2) ) and docetaxel (50 mg/m(2) ) on day 8 every 3
      weeks. Serum DAO activity was measured by colorimetry. Gastrointestinal toxicity
      was evaluated by Common Toxicity Criteria for Adverse Events version 4.0.
      Endoscopic examination and biopsy of duodenal mucosa assessed mucosal damage.
      Malnutrition was evaluated by measuring serum total protein and albumin levels.
      RESULTS: Serum DAO activity decreased step-by-step significantly during
      anticancer drug treatment and recovered after drug holidays. In all 14 patients
      who experienced diarrhea, serum DAO activity significantly decreased prior to
      diarrhea onset. Percent decrease in DAO activity was significantly correlated
      with severity of diarrhea. Significant correlation was observed between percent
      decrease in DAO activity and percent decrease in duodenal villus height or
      surface area from baseline. There were also significant correlations between
      percent decrease in serum DAO activity at day 14 and percent decrease in serum
      total protein or albumin levels at day 21 from baseline. CONCLUSION: Serum DAO
      activity sensitively indicates gastrointestinal damage prior to symptom onset and
      can be a useful predictor of intestinal mucosal damage and nutritional status in
      patients receiving chemotherapy.

PMID- 25968085
TI  - Increasing Colorectal Cancer Screening at Community-Based Primary Care Clinics in
      San Francisco.
AB  - CONTEXT: Adult colorectal cancer screening (CRCS) can lower disease incidence and
      mortality. However, widespread implementation is inconsistent, especially in the
      public sector. While specific interventions to increase CRCS have been
      identified, firsthand accounts of CRCS improvement efforts using multiple
      techniques in public sector settings are lacking. OBJECTIVE: A program evaluation
      was conducted to assess the effect of implementing a culture of continuous
      quality improvement (QI) on CRCS practices and prevalence. A multipronged
      incremental effort over more than a decade to increase CRCS at the San Francisco
      Department of Public Health is described. SETTING: Community-based primary care
      clinics. PARTICIPANTS: Departmental activities and 5 clinics providing full-scope
      primary care to CRCS-eligible adults who participated in departmental activities
      and outreach interventions were assessed. MAIN OUTCOME MEASURES: Departmental and
      clinic-specific CRCS activities and prevalence. RESULTS: Efforts included
      departmental prioritization; data-driven QI incorporating routine data sharing
      (monthly reports and data walls); departmental and clinic-specific QI committees;
      panel management (a team approach to generation of eligibility lists prior to
      scheduled visits, routinely offering screening during appointments or mailing
      test kits for patients without appointments); and departmental mail and phone
      outreach events. Screening ranged from 36.6% to 54.4% in 2010; in 2013, it ranged
      from 43.6% to 70.2%. Increases occurred consistently over that time in 3 of the 5
      clinics and ranged from 1.1% to 14.5%; decreases occurred during 2 intervals in 2
      clinics and ranged from 2.3% to 4.3%. CONCLUSION: CRCS prevalence can be markedly
      improved in the public sector with a data-driven panel management approach
      supported by departmental and clinic-specific QI committees and group outreach
      events. Continued prioritization of and focus on CRCS is required to ensure long
      term success. Even small increases will result in avoidable morbidity and
      mortality associated with this highly preventable disease.

PMID- 25968086
TI  - A Matter of Perspective: Seeing Cuban and United States' Health Systems Through a
      Cultural Lens.

PMID- 25968088
TI  - Lack of visual field asymmetries for spatial cueing in reading parafoveal Chinese
      characters.
AB  - In two experiments, we investigated whether visual field (VF) asymmetries of
      spatial cueing are involved in reading parafoveal Chinese characters. These
      characters are different from linearly arranged alphabetic words in that they are
      logograms that are confined to a constant, square-shaped area and are composed of
      only a few radicals. We observed a cueing effect, but it did not vary with the VF
      in which the Chinese character was presented, regardless of whether the cue
      validity (the ratio of validly to invalidly cued targets) was 1:1 or 7:3. These
      results suggest that VF asymmetries of spatial cueing do not affect the reading
      of parafoveal Chinese characters, contrary to the reading of alphabetic words.
      The mechanisms of spatial attention in reading parafoveal English-like words and
      Chinese characters are discussed. 

PMID- 25968087
TI  - GRAPES-Grounding representations in action, perception, and emotion systems: How
      object properties and categories are represented in the human brain.
AB  - In this article, I discuss some of the latest functional neuroimaging findings on
      the organization of object concepts in the human brain. I argue that these data
      provide strong support for viewing concepts as the products of highly interactive
      neural circuits grounded in the action, perception, and emotion systems. The
      nodes of these circuits are defined by regions representing specific object
      properties (e.g., form, color, and motion) and thus are property-specific, rather
      than strictly modality-specific. How these circuits are modified by external and
      internal environmental demands, the distinction between representational content
      and format, and the grounding of abstract social concepts are also discussed.

PMID- 25968089
TI  - Beyond left and right: Automaticity and flexibility of number-space associations.
AB  - Close links exist between the processing of numbers and the processing of space:
      relatively small numbers are preferentially associated with a left-sided response
      while relatively large numbers are associated with a right-sided response (the
      SNARC effect). Previous work demonstrated that the SNARC effect is triggered in
      an automatic manner and is highly flexible. Besides the left-right dimension,
      numbers associate with other spatial response mappings such as close/far
      responses, where small numbers are associated with a close response and large
      numbers with a far response. In two experiments we investigate the nature of this
      association. Associations between magnitude and close/far responses were observed
      using a magnitude-irrelevant task (Experiment 1: automaticity) and using a
      variable referent task (Experiment 2: flexibility). While drawing a strong
      parallel between both response mappings, the present results are also informative
      with regard to the question about what type of processing mechanism underlies
      both the SNARC effect and the association between numerical magnitude and
      close/far response locations. 

PMID- 25968090
TI  - Validation of the Tuebingen CD-25 Inventory as a Measure of Postoperative Health
      Related Quality of Life in Patients Treated for Cushing's Disease.
AB  - BACKGROUND: To evaluate the construct and criterion validity of the Tuebingen
      Cushing's disease quality of life inventory (Tuebingen CD-25) for application in
      patients treated for Cushing's disease (CD). METHODS: A total of 176 patients
      with adrenocorticotropin hormone-dependent CD (144 of them female, overall mean
      age 46.1 +/- 13.7 years) treated at 3 large tertiary referral centers in Germany
      were studied. Construct validity was assessed by hypothesis testing (self
      perceived symptom reduction assessment) and contrasted groups (patients with vs.
      without hypercorticolism). For this purpose, already existing data from 55 CD
      patients was used, representing the hypercortisolemic group. Criterion validity
      (concurrent validity) was assessed in relation to the Cushing's quality of life
      questionnaire (CushingQoL), the Short Form 36 health survey (SF-36), and the body
      mass index (BMI). RESULTS: Patients with self-perceived remarkable symptom
      reduction had significant lower Tuebingen CD-25 scores (i.e. better health
      related quality of life) than patients with self-perceived insufficient symptom
      reduction (p < 0.05). Similarly, the mean scores of the Tuebingen CD-25 scales
      were lower in patients without hypercortisolism (total score 27.0 +/- 17.2)
      compared to those with hypercortisolism (total score 45.3 +/- 22.1; each p <
      0.05), providing evidence for construct validity. Criterion validity was
      confirmed by the correlations between the Tuebingen CD-25 total score and the
      CushingQoL (Spearman's coefficient -0.733), as well as all scales of the SF-36
      (Spearman's coefficient between -0.447 and -0.700). CONCLUSION: The analyses
      presented in this large-sample study provide robust evidence for the construct
      and criterion validity of the Tuebingen CD-25.

PMID- 25968091
TI  - The emerging role of inhibitor of growth 4 as a tumor suppressor in multiple
      human cancers.
AB  - Inhibitor of growth 4 (ING4), a member of the conserved ING family, has been
      identified as an important tumor suppressor since it plays a critical role in the
      regulation of chromatin modification, cell proliferation, angiogenesis and cell
      migration. Some observations suggest that ING4 acts as a key regulator of
      tumorigenesis through modifying gene transcription in part by regulating the
      transcription factors p53 and NF-kappaB (NF-kappaB). However, these models have
      yet to be substantiated by further investigations. Numerous reports describe the
      reduced expression of ING4 in cancers, and the responsible mechanisms are
      involved in gene deletion, mutation, transcriptional and post-transcriptional
      dysregulation. This review aims to summarize the recent published literature that
      investigates the role of ING4 in regulating tumorigenesis and progression, and
      explore its potential for cancer treatment.

PMID- 25968092
TI  - Validation of Transtek blood pressure monitor TMB-1491 for self-measurement
      according to the European Society of Hypertension International Protocol revision
      2010.
AB  - OBJECTIVE: Transtek blood pressure monitor TMB-1491 is an automatic upper arm
      device designed for self/home measurement in adult populations. This study aimed
      to evaluate its accuracy according to the European Society of Hypertension
      International Protocol revision 2010. METHODS: The protocol requirements were
      followed precisely with the recruitment of 33 adult individuals on whom same-left
      arm sequential systolic blood pressure (SBP) and diastolic blood pressure (DBP)
      were measured. According to the validation protocol, 99 pairs of test device and
      reference blood pressure measurements were obtained in this study (three pairs
      for each of the 33 participants). RESULTS: The device produced 74, 95 and 99
      measurements within 5, 10, and 15 mmHg for SBP and 85, 97, and 99 for DBP,
      respectively. The mean+/-SD device-observer difference was -0.6+/-4.4 mmHg for
      SBP and -0.6+/-3.4 mmHg for DBP. The number of participants with two or three
      device-observer difference within 5 mmHg was 24 for SBP and 29 for DBP. In
      addition, none of the participants had a device-observer difference within 5 mmHg
      for SBP, and three of the participants had the same for DBP. CONCLUSION: Transtek
      TMB-1491 has passed all phases of European Society of Hypertension International
      Protocol revision 2010 and can be recommended for self/home measurement in adult
      populations.

PMID- 25968093
TI  - Validation of the Andon KD-5965 upper-arm blood pressure monitor for home blood
      pressure monitoring according to the European Society of Hypertension
      International Protocol revision 2010.
AB  - OBJECTIVE: This study aimed to evaluate the accuracy of the Andon KD-5965 upper
      arm blood pressure monitor according to the European Society of Hypertension
      International Protocol revision 2010. METHODOLOGY: Systolic and diastolic blood
      pressures were sequentially measured in 33 adults, with 20 women using a mercury
      sphygmomanometer (two observers) and the Andon KD-5965 device (one supervisor). A
      total of 99 pairs of comparisons were obtained from 33 participants for judgments
      in two parts with three grading phases. RESULTS: The device achieved the targets
      in part 1 of the validation study. The number of absolute differences between the
      device and observers within 5, 10, and 15 mmHg was 70/99, 91/99, and 98/99,
      respectively, for systolic blood pressure and 81/99, 99/99, and 99/99,
      respectively, for diastolic blood pressure. The device also fulfilled the
      criteria in part 2 of the validation study. Twenty-five and 29 participants, for
      systolic and diastolic blood pressure, respectively, had at least two of the
      three device-observers differences within 5 mmHg (required>=24). Two and one
      participants for systolic and diastolic blood pressure, respectively, had all
      three device-observers comparisons greater than 5 mmHg. CONCLUSION: According to
      the validation results, with better performance for diastolic blood pressure than
      that for systolic blood pressure, the Andon automated oscillometric upper-arm
      blood pressure monitor KD-5965 fulfilled the requirements of the European Society
      of Hypertension International Protocol revision 2010, and hence can be
      recommended for blood pressure measurement in adults.

PMID- 25968094
TI  - Total atrial conduction time evaluated with tissue Doppler imaging increases in
      hypertensive patients with hyperuricemia.
AB  - BACKGROUND: Serum uric acid (SUA) is an independent predictor of cardiovascular
      events in patients with hypertension. Total atrial conduction time (TACT) is a
      novel echocardiographic parameter used to identify the presence of electrical and
      structural atrial remodeling. We hypothesized that elevated SUA levels may be
      associated with prolonged TACT. METHODS: A total of 50 consecutive hyperuricemic
      (defined as SUA>7 mg/dl for men and >6.0 mg/dl for women) patients who had
      hypertension were included in the study. A total of 42 normouricemic patients
      were also recruited consecutively as the control group. All patients were
      evaluated by two-dimensional echocardiography and TACT was estimated by measuring
      the time delay between the onset of the P-wave of ECG and peak A'-wave on the
      tissue Doppler imaging (TDI) of the left atrial lateral wall (PA-TDI duration).
      RESULTS: There were no significant differences between the two groups according
      to age, sex, left ventricular systolic function, left atrial diameter, and
      systolic and diastolic blood pressure values. PA-TDI duration was found to be
      significantly increased in the hyperuricemic group (112.3+/-14.7 vs. 92+/-12.7
      ms; P<0.001) and positively correlated with the mean value of SUA levels (r=0.48,
      P<0.001). CONCLUSION: TACT increases in patients with hyperuricemia. Certainly,
      larger studies in different populations should further examine this potential
      association.

PMID- 25968095
TI  - A modified culture strategy of human keratinocytes to shorten the primary culture
      time.
AB  - Shortening time from biopsy to graft preparation is crucial for the coverage of
      extensive burn wound in major burn patients. This study was aimed to shorten the
      culture time of keratinocytes by means of one modified cell culture method. Three
      factors (temperature of dispase, area of skin, and age of patient) that might
      have impacts on cell behavior were evaluated. The results showed that cells
      isolated with dispase at 37 degrees C exhibited an improved cell activity than
      being isolated at 4 degrees C. The time that cells reached subconfluence with
      various skin areas was in order of 3 cm(2)  < 2 cm(2)  < 1 cm(2) (120.07 +/- 5.03
      h, 141.33 +/- 4.16 h, and 193.33 +/- 6.11 h, respectively). Furthermore, compared
      with the young and middle-aged groups, proliferation of keratinocytes isolated
      from children skin tissue was better. These results indicated that 3 cm(2) skin
      biopsy from a young patient, isolated with dispase at 37 degrees C, was a
      promising strategy to shorten the cultivation of keratinocytes. 

PMID- 25968096
TI  - Regressing Eruptive Disseminated Spitz Nevi.
AB  - The eruptive disseminated form of Spitz nevi (EDSN) is the rarest variant, is
      cosmetically disabling, and has a poorly documented natural history. We report
      the case of a 4-year-old boy with more than 100 Spitz nevi that have
      significantly regressed 8 years after onset. There is no satisfactory treatment
      for EDSN. There have been no reports of supervening malignancy. Our case
      illustrates the possibility of regression of EDSN, corroborating long-term
      observation as a safe and acceptable management option. 

PMID- 25968097
TI  - Physical Status and Variant Analysis of Human Papillomavirus 16 in Women from
      Shanghai.
AB  - BACKGROUND/AIMS: Human papillomavirus type 16 (HPV16) is the cause of more than
      half of all cases of cervical cancer. Genetic mutations in HPV16 and the
      integration of HPV16 DNA in the human genome are considered important genetic
      changes in cervical lesion progression. However, limited data concerning HPV16
      lineages and physical integration status have been reported for Shanghai, China.
      The current study analyzed the genetic mutations in complete HPV16 genomes and
      the physical integration status of HPV16 DNA. METHODS: A total of 30 samples of
      cervical exfoliated cells from patients with HPV16 infection were collected. The
      entire HPV16 genome was isolated, amplified by PCR and directly sequenced. The
      physical integration status was determined by 3'RACE nested PCR. RESULTS: A total
      of 13 integration sites were identified, including 9 in common fragile sites and
      1 not close to any fragile sites. Phylogenetic analysis identified two HPV
      lineages: the European (E) lineage and the East Asian (EA) lineage. Amino acid
      changes of D25E and N29S were the most common variations across the genome. The
      HPV16 early genes E1 and E7 and the late gene L1 tended to be highly conserved,
      whereas the early genes E2, E4 and E6 were more variable. Furthermore, 10 novel
      variations were identified in this study, which led to the 3 amino acid changes
      of S23I in E2 and E244K and T269I in E2/E4. CONCLUSION: Integrated HPV16 viruses
      were detected in all stages of cervical samples. Many variants in E2, E4, E7, and
      the long control region co-varied with E6 variations and helped to define the
      HPV16 lineages.

PMID- 25968098
TI  - Assessing and simulating the major pathway and hydrogeochemical transport of
      arsenic in the Beitou-Guandu area, Taiwan.
AB  - This study involved assessing and simulating the probable major pathways (surface
      and subsurface flow) and hydrogeochemical transport of arsenic (As) in the Beitou
      Guandu area, Taiwan. A one-dimensional (1-D) generic, reactive, chemical
      transport model (PHREEQC) was adopted. The calibrated model showed that As
      transported to the downstream Guandu plain and Tan Shui river mouth accounted for
      50.7 and approximately 100 % of the As in the subsurface flow pathway,
      respectively, suggesting that subsurface flow constituted a major As pathway. The
      highest As water concentration occurred near the Beitou geothermal valley because
      of the low pH and high redox potential in both the surface and subsurface
      pathways. However, As may be scavenged by aqueous Fe(II) in a reducing
      environment. The As concentrations in the downstream Guandu plain and Guandu
      wetland decreased as the simulated time increased, resulting in the adsorption of
      As on the surface of Fe oxydroxides and limiting the mobility of As in the
      surface flow pathway. The major retardation mechanism of As mobility in the
      subsurface flow pathway of the Guandu plain and Guandu wetland was governed by
      the adsorption reactions of iron-oxide and iron-sulfide minerals. The 1-D
      transport model was applied to predict the evolution of As in the subsurface flow
      pathway from 2013 to 2020. The results indicated that the As concentrations in
      all cells gradually increased. The geochemical redox reactions of As in the
      subsurface pathway subsequently led to the oxidization of As-bearing sulfides,
      causing As concentrations to rise substantially in the hillside area. 

PMID- 25968099
TI  - Resting state brain activity in patients with migraine: a magnetoencephalography
      study.
AB  - BACKGROUND: Recent advances in migraine research have shown that the cerebral
      cortex serves a primary role in the pathogenesis of migraine. Since aberrant
      brain activity in migraine can be noninvasively detected with
      magnetoencephalography (MEG), The object of this study was to investigate the
      resting state cortical activity differences between migraineurs and controls and
      its related clinical characteristics. METHODS: Twenty-two subjects with an acute
      migraine and twenty-two age- and gender-matched controls were studied using MEG.
      MEG recordings were recorded 120 seconds during the headache attack. Analyze MEG
      signals from low (1-4 Hz) to high (200-1000 Hz)-frequency ranges. RESULTS: In
      comparison with the controls, brain activity in migraine subjects was
      significantly different from that of the controls both in two frequency ranges
      (55-90 Hz, p < 0.001) and (90-200 Hz, p < 0.004). But the power value showed no
      significantly differences between control and migraines in all frequency ranges
      (p > 0.05). All the clinical characteristics had no significant correlation with
      aberrant brain activity. CONCLUSIONS: The results demonstrated that migraine
      subjects in resting state had significantly aberrant ictal brain activity that
      can be measured with neuromagnetic imaging techniques. The findings may
      facilitate the development of new therapeutic strategies in migraine treatment
      via alterations in cortical excitability with TMS and other medications in the
      future.

PMID- 25968100
TI  - Postoperative hemicrania continua-like headache - a case series.
AB  - BACKGROUND: Hemicrania continua (HC) is a rare chronic headache disorder,
      typically accompanied by cranial autonomic features and responding to therapeutic
      doses of indomethacin. The pathophysiology of hemicrania continua is not fully
      understood. FINDINGS: We report a series of three patients who developed a
      continuous hemicranial headache after cranial surgery. Each case presented a
      similar phenotype of continuous half-sided headache, cranial autonomic symptoms
      with exacerbations (2/3), and a response to indomethacin. CONCLUSION: The biology
      of hemicrania continua may be activated post-craniotomy just as can be seen with
      other primary headache disorders.

PMID- 25968101
TI  - Hemodynamic characteristics of high-altitude headache following acute high
      altitude exposure at 3700 m in young Chinese men.
AB  - BACKGROUND: This study aimed to identify the systemic and cerebral hemodynamic
      characteristics and their roles in high-altitude headache (HAH) among young
      Chinese men following acute exposure. METHODS: The subjects (n = 385) were
      recruited in June and July of 2012. They completed case report form
      questionnaires, as well as heart rate (HR), blood pressure, echocardiogram and
      transcranial Doppler examinations at 3700 m following a two-hour plane flight. A
      subgroup of 129 participants was examined at two altitudes (500 and 3700 m).
      RESULTS: HAH was characterized by increased HR and cardiac output (CO) and lower
      saturation pulse oxygen (SpO(2)) (all p < 0.05). The change in tricuspid
      regurgitation was also different between the HAH positive (HAH+) and HAH negative
      (HAH-) subjects. Furthermore, the HAH+ subjects exhibited faster mean (V(m)),
      systolic (V(s)) and diastolic (V(d)) velocities in the basilar artery (BA; all p
      < 0.05) and a faster V(d) ( 25.96 +/- 4.97 cm/s vs. 24.76 +/- 4.76 cm/s, p =
      0.045) in the left vertebral artery (VA). The bilateral VA asymmetry was also
      significantly different between the two groups. The pulsatility index (PI) and
      resistance index (RI) of left VA were lower in the HAH subjects (p < 0.05) and
      were negatively correlated with HAH (p < 0.05). Baseline CO and Vm in left VA (or
      right MCA in different regressions) were independent predictors for HAH, whereas
      CO/HR and DeltaV(d) (V(d) difference between bilateral VAs) were independent risk
      factors for HAH at 3700 m. CONCLUSIONS: HAH was characterized, in part, by
      increased systemic hemodynamics and posterior cerebral circulation, which was
      reflected by the BA and left VA velocities, and lower arterial resistance and
      compliance. Furthermore, baseline CO and V(m) in left VA or right MCA at sea
      level were independent predictors for HAH, whilst bilateral VA asymmetry may
      contribute to the development of HAH at high altitude.

PMID- 25968102
TI  - Osmophobia and allodynia are critical factors for suicidality in patients with
      migraine.
AB  - BACKGROUND: Sensory hypersensitivities are common phenomena in migraine. We
      examined the role of sensory hypersensitivities on suicidality in patients with
      migraine. METHODS: Patients with migraine (with or without aura) were
      consecutively recruited from our headache clinic. We asked them if they
      experienced photophobia, phonophobia, osmophobia, and allodynia during migraine
      attack. The Mini International Neuropsychiatric Interview was used to diagnose
      current major depressive disorder (MDD), current generalized anxiety disorder
      (GAD) and suicidality. RESULTS: Among 220 subjects, 25.5 % had current MDD, 17.3
      % had current GAD, and 31.8 % had suicidality. Patients with suicidality were
      more like to have a low household income, chronic migraine (CM), medication
      overuse headache, high headache intensity, osmophobia, allodynia, high
      disability, MDD, and GAD than those without suicidality. The strongest risk
      factor for suicidality by multivariate analyses was osmophobia (adjusted Odds
      Ratio [AOR] 3.12, 95 % confidence interval [CI] 1.57-6.21, p = 0.001), followed
      by current MDD (AOR 2.99, 95 % CI 1.33-6.76, p = 0.008), CM (AOR 2.48, 95 % CI
      1.21-5.09, p = 0.013), current GAD (AOR 3.11, 95 % CI 1.22-7.91, p = 0.017), and
      allodynia (AOR 2.72, 95 % CI 1.19-6.21, p = 0.018). CONCLUSIONS: Osmophobia and
      allodynia are critical factors for suicidality in patients with migraine, after
      controlling for depression, anxiety, and CM.

PMID- 25968103
TI  - Cardiac Rehabilitation after an Acute Coronary Syndrome: The Impact in Elderly
      Patients.
AB  - INTRODUCTION: Cardiac rehabilitation (CR) has been shown to decrease mortality
      and morbidity, improve the control of risk factors and the quality of life of
      patients with coronary artery disease. However, the elderly are underrepresented
      in most studies and in real-life CR programs. Our goal was to evaluate the impact
      of CR after an acute coronary syndrome in the elderly population. METHODS: A
      cutoff of 65 years was used to dichotomize age. Our main focus was on the effects
      of ambulatory supervised exercise training on several surrogate markers, namely
      total cholesterol, low- and high-density lipoprotein cholesterol, triglycerides,
      body mass index, fasting glucose, glycated hemoglobin, probrain natriuretic
      peptide, International Physical Activity Questionnaire score, maximal exercise
      capacity, chronotropic response index and heart rate recovery. We evaluated those
      variables at the beginning and at the end of phase II of the CR program (after 3
      months) and repeated the treadmill test at 12 months. RESULTS: A total of 548
      patients with a recent acute coronary syndrome were enrolled; 37% were 65 years
      old or older. Both age groups had a statistically significant improvement in all
      the evaluated parameters. Interestingly, at 12 months both groups maintained the
      improvement in functional capacity seen immediately after 3 months. CONCLUSIONS:
      The benefits of CR in terms of functional capacity, metabolic profile and other
      prognostic parameters were significant in both younger and older patients.
      Therefore, all eligible patients should be referred to CR programs, irrespective
      of age.

PMID- 25968104
TI  - HIV infection is associated with an increased prevalence of coronary noncalcified
      plaque among participants with a coronary artery calcium score of zero:
      Multicenter AIDS Cohort Study (MACS).
AB  - OBJECTIVES: HIV-infected individuals bear increased cardiovascular risk even in
      the absence of traditional cardiovascular risk factors. In the general
      population, coronary artery calcium (CAC) scanning is of value for cardiovascular
      risk stratification, but whether a CAC score of zero implies a low noncalcified
      coronary plaque burden in HIV-infected persons is unknown. METHODS: We assessed
      the prevalence of noncalcified coronary plaque and compared noncalcified coronary
      plaque burden between HIV-infected and HIV-uninfected participants who had CAC
      scores of zero in the Multicenter AIDS Cohort Study (MACS) using coronary
      computed tomography (CT) angiography. RESULTS: HIV infection was associated with
      the presence of noncalcified coronary plaque among these men with CAC scores of
      zero. In a model adjusted only for age, race, centre, and pre- or post-2001
      cohort, the prevalence ratio for the presence of noncalcified plaque was 1.27
      (95% confidence interval 1.04-1.56; P = 0.02). After additionally adjusting for
      cardiovascular risk factors, HIV infection remained associated with the presence
      of noncalcified coronary plaque (prevalence ratio 1.31; 95% confidence interval
      1.07-1.6; P = 0.01). CONCLUSIONS: Among men with CAC scores of zero, HIV
      infection is associated with an increased prevalence of noncalcified coronary
      plaque independent of traditional cardiovascular risk factors. This finding
      suggests that CAC scanning may underestimate plaque burden in HIV-infected men.

PMID- 25968105
TI  - Transcriptome of an entomophthoralean fungus (Pandora formicae) shows molecular
      machinery adjusted for successful host exploitation and transmission.
AB  - Pandora formicae is an obligate entomopathogenic fungus from the phylum
      Entomophthoromycota, known to infect only ants from the genus Formica. In the
      final stages of infection, the fungus induces the so-called summit disease
      syndrome, manipulating the host to climb up vegetation prior to death and fixing
      the dead cadaver to the surface, all to increase efficient spore dispersal. To
      investigate this fascinating pathogen-host interaction, we constructed
      interaction transcriptome libraries from two final infection stages from the
      material sampled in the field: (1) when the cadavers were fixed, but the fungus
      had not grown out through the cuticle and (2) when the fungus was growing out
      from host cadaver and producing spores. These phases mark the switch from within
      host growth to reproduction on the host surface, after fungus outgrowth through
      host integument. In this first de novo transcriptome of an entomophthoralean
      fungus, we detected expression of many pathogenicity-related genes, including
      secreted hydrolytic enzymes and genes related to morphological reorganization and
      nutrition uptake. Differences in expression of genes in these two infection
      phases were compared and showed a switch in enzyme expression related to either
      cuticle breakdown or cell proliferation and cell wall remodeling, particularly in
      subtilisin-like serine protease and trypsin-like protease transcripts. 

PMID- 25968106
TI  - Yearly, pond, lineage and family variation of hepatopancreatic parvo-like virus
      (HPV) copy number in banana shrimp Fenneropenaeus merguiensis.
AB  - Hepatopancreatic parvo-like virus (HPV) has been reported from a variety of
      shrimp species around the world, including Australia, and thought to impact
      negatively on production, but until now there was scant information available on
      variation of HPV over time, ponds and shrimp lineages or families, information
      that could be used to manage or reduce virus levels. Here we report HPV copy
      number estimated using qPCR from 1500 individual shrimp sampled over three years
      and encompassing 91 ponds, 21 breeding groups or lineages and 40 families. HPV
      copy number variation between ponds was used by farm management as a criterion to
      choose prospective broodstock (candidates were taken from low HPV ponds). Despite
      such choice, HPV levels in farmed animals were not reduced from 2011 to 2013.
      Accordingly, the hypothesis that HPV levels can be reduced over time simply by
      considering average HPV levels in ponds alone is rejected. Different lines of
      shrimp within the same farm had different HPV levels, but as lines were raised
      separately, the line differences could be due to either genetic or environmental
      differences, the latter including possible different rearing effects and
      differences in vertical transmission. There were large (up to 2-3 LOG fold)
      differences of HPV levels between families bred and grown together
      contemporaneously, and the heritability for HPV copy number was estimated to be
      moderate to large (0.40 +/- 0.13). Apart from genetic differences, differences of
      vertical transmission from dams may contribute to the between family differences,
      in any case we postulate that selection between families could be an effective
      method to reduce HPV levels. HPV levels were not genetically correlated with
      performance traits such as body weight or length, so selection for HPV level
      should not adversely affect production characteristics. This is the first
      evidence for an aquacultured species that viral levels, as opposed to
      survival/resistance to viruses, may have a substantial host genetic component.
      The heritability reported here for virus copy number was higher that most
      heritabilities reported for survival to specific pathogens such as white spot,
      raising the general postulate that selection for virus copy number may be more
      effective and repeatable than selection for survival to pathogen challenge.

PMID- 25968107
TI  - Brief report: Attention to positive information mediates the relationship between
      hope and psychosocial well-being of adolescents.
AB  - This study tested the mediating roles of cognitive reappraisal and attentional
      preferences in the relationship between hope and psychosocial well-being among
      712 adolescents. Results of the structural equation modeling revealed that the
      beneficial relation of hope to subjective happiness, anxiety, depressive
      symptoms, and interpersonal difficulties was partially mediated by attention to
      positive information but not cognitive reappraisal. Findings of this study may
      inform the design of intervention research by highlighting the importance of
      hopeful thinking style and attention to positive information in mental health of
      adolescents. 

PMID- 25968108
TI  - Relationships between perceived teachers' controlling behaviour, psychological
      need thwarting, anger and bullying behaviour in high-school students.
AB  - We tested a model of the associations between students' perceptions of their
      physical education teacher's controlling behaviour, perceptions of basic
      psychological need thwarting, anger and bullying behaviour. School students (N =
      602; M age = 12.88, SD = 1.37) from 10 schools completed measures of perceived
      teachers' controlling behaviour and perceived thwarting of the psychological
      needs for autonomy, competence, and relatedness in physical education context and
      self-reported bullying and anger. A well-fitting structural equation model
      demonstrated that students' perceptions of the negative conditional regard and
      intimidation exhibited by the teacher had significant indirect effect on
      students' feelings of anger and bullying behaviour through the perceived
      psychological need thwarting in physical education. Findings suggest that
      physical education teachers who avoid the use of negative conditional regard and
      intimidation in their classes have students who perceive less need thwarting and
      report less bullying behaviour. 

PMID- 25968110
TI  - Targeting VEGF with LNA-stabilized G-rich oligonucleotide for efficient breast
      cancer inhibition.
AB  - In this study, we investigated the efficacy of an LNA (locked nucleic acid)
      modified DNA aptamer named RNV66 targeting VEGF against various breast cancer
      cell lines. Our results demonstrate that RNV66 efficiently inhibits breast cancer
      cell proliferation both in vitro and in vivo. Introduction of LNA nucleotides
      were crucial for higher efficacy. Furthermore, the binding interaction of RNV66
      with VEGF was investigated using molecular dynamic simulations leading to the
      first computational model of the LNA aptamer-VEGF complex blocking its
      interaction with VEGF-receptor. 

PMID- 25968111
TI  - Improving compliance with central venous catheter care bundles using electronic
      records.
AB  - BACKGROUND: Health care associated infections are a major contributor to
      avoidable harm experienced by patients in modern health care settings. Recent
      reports suggest that electronic checklists for the documentation of a central
      line bundle may significantly enhance documented process compliance and help to
      reduce catheter-related bloodstream infection rates. AIMS: This paper describes
      the use of our electronic tool to monitor and feedback process compliance in
      conjunction of introducing bespoke central line insertion packs to tackle
      catheter-related bloodstream infections in our intensive care unit in a medium
      sized district general hospital. DESIGN AND METHODS: Continuous quality
      improvement programme with 'Plan-Do-Study-Act' cycles was implemented. The
      central venous catheter insertion and maintenance bundle was rolled out in 2007.
      To monitor compliance with the bundle elements, an electronic tool was designed
      as part of our bedside Clinical Information System. From 2009, regular quarterly
      feedback was provided on the number of central venous catheter lines inserted,
      compliance with the insertion and maintenance bundle and catheter-related
      bloodstream infection rate using the data collected through the Clinical
      Information System. We have also introduced dedicated line insertion trolleys and
      factory-prepared insertion packs. We used segmented regression analysis to assess
      the changes in the catheter-related bloodstream infection rate before and after
      implementation of the central venous catheter bundle. RESULTS: Bundle compliance
      increased during the implementation period and reached over 95% within 6 months.
      We observed a significant reduction in the catheter-related bloodstream infection
      rate from 15.6/1000 days to 0.4/1000 days. Regression analysis showed that only
      the compliance had significant effect on the number and prevalence of catheter
      related bloodstream infections. CONCLUSION/IMPLICATIONS: Implementation of
      evidence-based care bundles reinforced by real-time feedback on the performance
      of caregivers can significantly reduce the rate of catheter-related bloodstream
      infection in the intensive care unit. Ensuring that change processes are
      seamlessly integrated in the workflow with minimal administrative burden is
      crucial to the quality improvement process.

PMID- 25968112
TI  - Short- and medium-term effects of informal care provision on female caregivers'
      health.
AB  - In this paper, we present estimates of the effect of informal care provision on
      female caregivers' health. We use data from the German Socio-Economic Panel and
      assess effects up to seven years after care provision. The results suggest that
      there is a considerable negative short-term effect of informal care provision on
      mental health which fades out over time. Five years after care provision the
      effect is still negative but smaller and insignificant. Both short- and medium
      term effects on physical health are virtually zero throughout. A simulation
      analysis is used to assess the sensitivity of the results with respect to
      potential deviations from the conditional independence assumption in the
      regression adjusted matching approach. 

PMID- 25968113
TI  - Domain similarity based orthology detection.
AB  - BACKGROUND: Orthologous protein detection software mostly uses pairwise
      comparisons of amino-acid sequences to assert whether two proteins are
      orthologous or not. Accordingly, when the number of sequences for comparison
      increases, the number of comparisons to compute grows in a quadratic order. A
      current challenge of bioinformatic research, especially when taking into account
      the increasing number of sequenced organisms available, is to make this ever
      growing number of comparisons computationally feasible in a reasonable amount of
      time. We propose to speed up the detection of orthologous proteins by using
      strings of domains to characterize the proteins. RESULTS: We present two new
      protein similarity measures, a cosine and a maximal weight matching score based
      on domain content similarity, and new software, named porthoDom. The qualities of
      the cosine and the maximal weight matching similarity measures are compared
      against curated datasets. The measures show that domain content similarities are
      able to correctly group proteins into their families. Accordingly, the cosine
      similarity measure is used inside porthoDom, the wrapper developed for
      proteinortho. porthoDom makes use of domain content similarity measures to group
      proteins together before searching for orthologs. By using domains instead of
      amino acid sequences, the reduction of the search space decreases the
      computational complexity of an all-against-all sequence comparison. CONCLUSION:
      We demonstrate that representing and comparing proteins as strings of discrete
      domains, i.e. as a concatenation of their unique identifiers, allows a drastic
      simplification of search space. porthoDom has the advantage of speeding up
      orthology detection while maintaining a degree of accuracy similar to
      proteinortho. The implementation of porthoDom is released using python and C++
      languages and is available under the GNU GPL licence 3 at
      http://www.bornberglab.org/pages/porthoda .

PMID- 25968114
TI  - Antimicrobial properties of nanomolecules: potential candidates as antibiotics in
      the era of multi-drug resistance.
AB  - OBJECTIVES: The emergence of multi-drug resistance among various microbial
      pathogens has been a cause of serious concern to the medical world, limiting the
      choice of antibiotics. Considering that it may take decades to synthesize new
      antimicrobial drugs that combat resistant pathogens, the search for alternatives
      to conventional antimicrobial agents has begun. METHODS: In his paper we
      attempted to review the physico-chemical properties of nanoparticles, their modes
      of action and potential use in medicine and research with special reference to
      antimicrobial properties. RESULTS: Nanomolecules and nanoparticles have in recent
      years been extensively studied for their utility not only as antibiotics but also
      as vehicles to carry antibiotics or other agents such as cancer chemotherapeutics
      to target sites and limit damage to host cells. CONCLUSION: Nanomolecules were
      positively evaluated for their antimicrobial activities. Anti-biofilm activities
      of nanoparticles, utility of nanomaterials as carrier agents of drugs signifies
      their importance in medicine and research.

PMID- 25968115
TI  - Disadvantages of publishing biomedical research articles in English for non
      native speakers of English.
AB  - OBJECTIVES: English has become the most frequently used language for scientific
      communication in the biomedical field. Therefore, scholars from all over the
      world try to publish their findings in English. This trend has a number of
      advantages, along with several disadvantages. METHODS: In the current article,
      the most important disadvantages of publishing biomedical research articles in
      English for non-native speakers of English are reviewed. RESULTS: The most
      important disadvantages of publishing biomedical research articles in English for
      non-native speakers may include: Overlooking, either unintentionally or even
      deliberately, the most important local health problems; failure to carry out
      groundbreaking research due to limited medical research budgets; violating
      generally accepted codes of publication ethics and committing research misconduct
      and publications in open-access scam/predatory journals rather than prestigious
      journals. CONCLUSIONS: The above mentioned disadvantages could eventually result
      in academic establishments becoming irresponsible or, even worse, corrupt. In
      order to avoid this, scientists, scientific organizations, academic institutions,
      and scientific associations all over the world should design and implement a
      wider range of collaborative and comprehensive plans.

PMID- 25968116
TI  - Admission route and use of invasive procedures during hospitalization for acute
      myocardial infarction: analysis of 2007-2011 National Health Insurance database.
AB  - OBJECTIVES: The goal of this study was to investigate trends in admission to the
      emergency department and the use of invasive or surgical procedures during
      hospitalization for acute myocardial infarction (AMI) in Korea. METHODS: The
      National Health Insurance (NHI) claims database between 2007 and 2011 was used.
      We identified all admission claims that included codes from the tenth revision of
      the International Classification of Diseases beginning with I21 as the primary or
      secondary diagnosis. Information about the admission route, admission date,
      discharge date, and whether coronary artery angiography, angioplasty, or bypass
      surgery was performed was also obtained from the NHI database. RESULTS: Of the
      513,886 relevant admission claims over the five years encompassed by this study,
      295,001 discrete episodes of admission for AMI were identified by analyzing the
      date and length of each admission and the interval between admissions. The number
      of AMI admissions gradually decreased from 66,883 in 2007 to 47,656 in 2011. The
      number and proportion of admissions through the emergency department also
      decreased from 38,118 (57.0%) in 2007 to 24,001 (50.4%) in 2011. However, during
      the same period, admissions in which invasive or surgical procedures were
      performed increased from 15,342 (22.9%) to 17,505 (36.7%). CONCLUSIONS: The
      reported numbers of emergency department visits and admissions for AMI decreased
      from 2007 to 2011. However, only a small portion of the patients underwent
      invasive or surgical procedures during hospitalization, although the number of
      admissions involving invasive or surgical procedures has increased. These
      findings suggest that simply counting the number of admission claims cannot
      provide valid information on trends in AMI occurrence.

PMID- 25968117
TI  - Study Reveals Target of Leukemia Drug.

PMID- 25968118
TI  - T-Cell-Based Immune Therapy Treats EBV-LPD.

PMID- 25968119
TI  - Striatal neuronal death mediated by astrocytes from the Gcdh-/- mouse model of
      glutaric acidemia type I.
AB  - Glutaric acidemia type I (GA-I) is an inherited neurometabolic childhood disorder
      caused by defective activity of glutaryl CoA dehydrogenase (GCDH) which disturb
      lysine (Lys) and tryptophan catabolism leading to neurotoxic accumulation of
      glutaric acid (GA) and related metabolites. However, it remains unknown whether
      GA toxicity is due to direct effects on vulnerable neurons or mediated by GA
      intoxicated astrocytes that fail to support neuron function and survival. As
      damaged astrocytes can also contribute to sustain high GA levels, we explored the
      ability of Gcdh-/- mouse astrocytes to produce GA and induce neuronal death when
      challenged with Lys. Upon Lys treatment, Gcdh-/- astrocytes synthetized and
      released GA and 3-hydroxyglutaric acid (3HGA). Lys and GA treatments also
      increased oxidative stress and proliferation in Gcdh-/- astrocytes, both
      prevented by antioxidants. Pretreatment with Lys also caused Gcdh-/- astrocytes
      to induce extensive death of striatal and cortical neurons when compared with
      milder effect in WT astrocytes. Antioxidants abrogated the neuronal death induced
      by astrocytes exposed to Lys or GA. In contrast, Lys or GA direct exposure on
      Gcdh-/- or WT striatal neurons cultured in the absence of astrocytes was not
      toxic, indicating that neuronal death is mediated by astrocytes. In summary, GCDH
      defective astrocytes actively contribute to produce and accumulate GA and 3HGA
      when Lys catabolism is stressed. In turn, astrocytic GA production induces a
      neurotoxic phenotype that kills striatal and cortical neurons by an oxidative
      stress-dependent mechanism. Targeting astrocytes in GA-I may prompt the
      development of new antioxidant-based therapeutical approaches.

PMID- 25968120
TI  - High-dose benzodiazepine dependence: a qualitative study of patients' perception
      on cessation and withdrawal.
AB  - BACKGROUND: Benzodiazepine withdrawal syndrome has been reported following
      attempts to withdraw even from low or therapeutic doses and has been compared to
      barbiturate and alcohol withdrawal. This experience is known to deter patients
      from future cessation attempts. Research on other psychotropic substances shows
      that the reasons and motivations for withdrawal attempts - as well as the
      experiences surrounding those attempts - at least partially predict future
      efforts at discontinuation as well as relapse. We therefore aimed to
      qualitatively explore what motivates patients to discontinue this medication as
      well as to examine their experiences surrounding previous and current withdrawal
      attempts and treatment interventions in order to positively influence future help
      seeking behavior and compliance. METHODS: To understand these patients better, we
      conducted a series of 41 unstructured, narrative, in-depth interviews among adult
      Swiss patients with a long-term dependent use of benzodiazepines in doses
      equivalent to more than 40 mg diazepam per day and/or otherwise problematic use
      (mixing benzodiazepines, escalating dosage, recreational use or illegal
      purchase). Mayring's qualitative content analysis was used to evaluate findings.
      RESULTS: These high-dose benzodiazepine-dependent patients decision to change
      consumption patterns were affected by health concerns, the feeling of being
      addicted and social factors. Discontinuation attempts were frequent and not very
      successful with fast relapse. Withdrawal was perceived to be a difficult,
      complicated, and highly unpredictable process. The first attempt at withdrawal
      occurred at home and typically felt better than at the clinic. Inpatient
      treatment was believed to be more effective with long term treatment (approaches)
      than short term. Patients preferred gradual reduction of usage to abrupt
      cessation (and had experienced both). While no clear preferences for withdrawal
      were found for benzodiazepines with specific pharmacokinetic properties,
      participants frequently based their decision to participate in treatment on the
      availability of their preferred brand name and furthermore discarding equivalent
      dosage rationales. CONCLUSIONS: Our findings provide greater understanding of the
      factors that motivate high-dose benzodiazepine-dependent individuals to stop
      taking these medications, and how they experience withdrawal and treatment
      strategies. They underscore how patients' perceptions of treatment approaches
      contribute to compliant or non-compliant behavior.

PMID- 25968121
TI  - Alcohol brief intervention for hospitalized veterans with hazardous drinking:
      protocol for a 3-arm randomized controlled efficacy trial.
AB  - BACKGROUND: Various hospital accreditation and quality assurance entities in the
      United States have approved and endorsed performance measures promoting alcohol
      brief intervention (BI) for hospitalized individuals who screen positive for
      unhealthy alcohol use, the spectrum of use ranging from hazardous use to alcohol
      use disorders. These performance measures have been controversial due to the
      limited and equivocal evidence for the efficacy of BI among hospitalized
      individuals. The few BI trials conducted with hospital inpatients vary widely in
      methodological quality. While the majority of these studies indicate limited to
      no effects of BI in this population, none have been designed to account for the
      most pervasive methodological issue in BI studies presumed to drive study
      findings towards the null: assessment reactivity (AR). METHODS/DESIGN: This is a
      three-arm, single-site, randomized controlled trial of BI for hospitalized
      patients at a large academic medical center affiliated with the U.S. Department
      of Veterans Affairs who use alcohol at hazardous levels but do not have an
      alcohol use disorder. Participants are randomized to one of three study
      conditions. Study Arm 1 receives a three-part alcohol BI. Study Arm 2 receives
      attention control. To account for potential AR, Study Arm 3 receives AC with
      limited assessment. Primary outcomes will include the number of standard
      drinks/week and binge drinking episodes reported in the 30-day period prior to a
      final measurement visit obtained 6 months after hospital discharge. Additional
      outcomes will include readiness to change drinking behavior and number of adverse
      consequences of alcohol use. To assess differences in primary outcomes across the
      three arms, we will use mixed-effects regression models that account for a
      patient's repeated measures over the timepoints and clustering within medical
      units. Intervention implementation will be assessed by: a) review of intervention
      audio recordings to characterize barriers to intervention fidelity; and b)
      feasibility of participant recruitment, enrollment, and follow-up. DISCUSSION:
      The results of this methodologically rigorous trial will provide greater
      justification for or against the use of BI performance measures in the inpatient
      setting and inform organizational responses to BI-related hospital accreditation
      and performance measures. TRIAL REGISTRATION: NCT01602172.

PMID- 25968122
TI  - Carotid Artery Applanation Tonometry Does Not Cause Significant Baroreceptor
      Activation.
AB  - BACKGROUND: Carotid artery applanation tonometry is widely used in estimating
      local carotid artery pressure waveforms and carotid-femoral pulse wave velocity.
      However, the substantial pressure applied locally to the carotid artery with
      applanation tonometry might well evoke a baroreceptor response, resulting in
      bradycardia and hypotension. Therefore, when carotid and femoral tonometry are
      performed sequentially, baroreceptor activation could lead to different
      hemodynamic conditions between carotid and femoral acquisitions. Combining those
      acquisitions into one pulse wave velocity measure would be erroneous. In this
      study, we assessed whether carotid applanation tonometry has an influence on
      heart rate and blood pressure. METHODS: In 26 hypertensive subjects, heart rate
      and blood pressure were assessed by continuous finger pulse waveform recording
      during carotid as well as femoral applanation tonometry. Both carotid and femoral
      acquisitions were measured in alternation and in triplicate. Median averaging
      over the 3 carotid and femoral measurements, respectively, was used to obtain a
      subject's median heart rate and blood pressure during carotid as well as femoral
      tonometry. RESULTS: Difference in heart rate during carotid and femoral tonometry
      was -0.7+/-2.2 bpm. Differences in systolic, pulse, and diastolic blood pressure
      were -0.7+/-6.8, -0.1+/-3.8, and -0.3+/-3.5mm Hg, respectively. All differences
      were statistically nonsignificant. Confidence intervals were used to calculate
      the maximum absolute difference at 95% certainty, which was 1.6 bpm for heart
      rate and <=3.5mm Hg for all blood pressures. CONCLUSIONS: We conclude that in our
      study, carotid artery applanation tonometry as performed by an experienced
      researcher did not cause clinically significant baroreceptor activation.

PMID- 25968123
TI  - Plasma and Kidney Angiotensin Peptides: Importance of the Aminopeptidase
      A/Angiotensin III Axis.
AB  - BACKGROUND: The renin-angiotensin system is a complex regulatory hormonal network
      with a main biological peptide and therapeutic target, angiotensin (Ang) II (1
      8). There are other potentially important Ang peptides that have not been well
      evaluated. METHODS: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was
      used for concurrent evaluation of multiple Angs downstream of Ang I (1-10) and
      Ang II (1-8) in kidney and plasma from wild-type (WT) mice. Angiotensin
      converting enzyme 2 knockout (ACE2KO) was also used as a way to examine the Angs
      profile in the absence of ACE2, an enzyme that cleaves both Ang I (1-10) and Ang
      II (1-8). RESULTS: In plasma from both WT and ACE2KO, levels of Ang I (1-10), Ang
      III (2-8), and Ang (2-10) were the highest of all the renin-angiotensin system
      (RAS) peptides. The latter two peptides are products of aminopeptidase A cleavage
      of Ang II (1-8) and Ang I (1-10), respectively. In contrast, plasma levels of Ang
      II (1-8), and Ang (1-7), the product of Ang II (1-8) cleavage by ACE2, were low.
      In kidney from both WT and ACE2KO, Ang II (1-8) levels were high as compared to
      plasma levels. In the ACE2KO mice, a significant increase in either Ang II (1-8)
      or a decrease in Ang (1-7) was not observed in plasma or in the kidney.
      CONCLUSION: RAS-focused peptidomic approach revealed major differences in Ang
      peptides between mouse plasma and kidney. These Ang peptide profiles show the
      dominance of the aminopeptidase A/Ang (2-10) and aminopeptidase A/Ang III (2-8)
      pathways in the metabolism of Ang I (1-10) and Ang II (1-8) over the ACE2/Ang (1
      7) axis. Ang III (2-8) and other peptides formed from aminopeptidase A cleavage
      may be important therapeutic RAS targets.

PMID- 25968124
TI  - Trends in Antihypertensive Medication Use and Blood Pressure Control Among Adults
      With Hypertension in Germany.
AB  - BACKGROUND: Hypertension is a major risk factor for morbidity and mortality,
      therefore its control is of great importance. In this study we compare the use of
      antihypertensive medication among adults with hypertension in Germany 1998 and
      2008-2011 and determine factors associated with use and control. METHODS: Data
      from German Health Examination Surveys (GNHIES98 1998, n = 7,124 and DEGS1 2008
      2011 n = 7,988, age 18-79 years) including standardized blood pressure (BP)
      measurements and Anatomical Therapeutic Chemical (ATC) medication codes were
      analyzed. RESULTS: The use of antihypertensive medication among adults with
      hypertension in Germany increased from 54% to 72% in 1 decade. In 2008-2011, 67%
      of users were treated with polytherapy. The most commonly used antihypertensive
      class in 1998 was diuretics (43%) and in 2008-2011 beta-blockers (54%). Ramipril
      and metoprolol are currently the most commonly used monotherapy agents, while
      ramipril in combination with hydrochlorothiazide is the most frequent
      polytherapy. Being a woman, older age, having statutory health insurance,
      diabetes, coronary heart disease (CHD), stroke, and obesity were positively
      associated with antihypertensive use. The control rate among treated increased
      from 42% to 72%. Young women (18-54 years) had better control compared to older
      women or to men. Having CHD or stroke was positively associated with BP control.
      CONCLUSIONS: Increased and improved antihypertensive use might be a main
      contributor to the decrease in BP observed in Germany in the last decade.
      However, there are still socio-demographic and health disparities in hypertension
      treatment and control.

PMID- 25968125
TI  - Erratum to: DNA methylation age of human tissues and cell types.

PMID- 25968126
TI  - The efficacy of a lysine-based dendritic hydrogel does not differ from those of
      commercially available tissue sealants and adhesives: an ex vivo study.
AB  - BACKGROUND: Hemostatic agents, tissue adhesives and sealants may contribute to a
      reduction in hemorrhage-associated morbidity and mortality. Towards this end, we
      have recently developed a lysine-based dendritic hydrogel (PEG-LysNH2) that can
      potentially be used in the management of severe trauma and/or intraoperative
      bleeding. As a first step in demonstrating the potential utility of this
      approach, our objective was to ascertain the ability of the PEG-LysNH2 to adhere
      to and seal injured tissues, as well as to maintain the seal under physiological
      conditions. METHODS: The efficacy of the PEG-LysNH2 in sealing injured tissues
      was evaluated using an ex-vivo pressure testing system. A 2.5 mm incision was
      made on intact ex-vivo tissues and then sealed with the PEG-LysNH2. Application
      of the PEG-LysNH2 was followed by 1) step-wise pressure increase to a maximum of
      250 mmHg and 2) fluctuating pressures, between 100-180 mmHg with a rate of 3 Hz,
      over a 24-hour period. The performance of the PEG-LysNH2 was compared to those of
      commercially available sealants and adhesives. RESULTS: During gradual pressure
      increase, mean pressures at 30 seconds (P30) ranged between 206.36 - 220.17 mmHg
      for the sealants, and they were greater than control and suture groups (p < 0.01
      and p = 0.013, respectively). Additionally, all products held under fluctuating
      pressures: mean pressures ranged between 135.20 - 160.09 mmHg, and there were no
      differences observed between groups (p = 0.96). CONCLUSIONS: The efficacy of the
      PEG-LysNH2 was significantly superior to conventional injury repair methods
      (sutures) and did not differ from those of commercially available products when
      sealing small incisions.

PMID- 25968127
TI  - A novel, cryopreserved, viable osteochondral allograft designed to augment marrow
      stimulation for articular cartilage repair.
AB  - BACKGROUND: Here, we describe the design and characterization of a novel,
      cryopreserved, viable osteochondral allograft (CVOCA), along with evidence that
      the CVOCA can improve outcomes of marrow stimulation for articular cartilage
      repair. METHODS: Histological staining was performed to evaluate the CVOCA tissue
      architecture. CVOCAs were tested for the presence of extracellular matrix (ECM)
      proteins and chondrogenic growth factors using ELISA. Cell viability and
      composition were examined via live/dead staining, fluorescence-activated cell
      sorting (FACS) analysis, and immunofluorescence staining. FACS analysis and a TNF
      alpha secretion bioassay were used to confirm the lack of immunogenic cells.
      Effects of the CVOCA on mesenchymal stem cells (MSCs) were tested using in vitro
      migration and chondrogenesis assays. The ability of the CVOCA to augment marrow
      stimulation in vivo was evaluated in a goat model. RESULTS: A method of tissue
      processing and preservation was developed resulting in a CVOCA with pores and
      minimal bone. The pores were found to increase the flexibility of the CVOCA and
      enhance growth factor release. Histological staining revealed that all three
      zones of hyaline cartilage were preserved within the CVOCA. Chondrogenic growth
      factors (TGF-beta1, TGF-beta3, BMP-2, BMP-4, BMP-7, bFGF, IGF-1) and ECM proteins
      (type II collagen, hyaluronan) were retained within the CVOCA, and their
      sustained release in culture was observed (TGF beta1, TGF-beta2, aggrecan). The
      cells within the CVOCA were confirmed to be chondrocytes and remained viable and
      functional post-thaw. Immunogenicity testing confirmed the absence of immunogenic
      cells. The CVOCA induced MSC migration and chondrogenesis in vitro. Experimental
      results using devitalized flash frozen osteochondral allografts revealed the
      importance of preserving all components of articular cartilage in the CVOCA.
      Goats treated with the CVOCA and marrow stimulation exhibited better repair
      compared to goats treated with marrow stimulation alone. CONCLUSIONS: The CVOCA
      retains viable chondrocytes, chondrogenic growth factors, and ECM proteins within
      the intact architecture of native hyaline cartilage. The CVOCA promotes MSC
      migration and chondrogenesis following marrow stimulation, improving articular
      cartilage repair.

PMID- 25968129
TI  - Early and late promoters of BK polyomavirus, Merkel cell polyomavirus,
      Trichodysplasia spinulosa-associated polyomavirus and human polyomavirus 12 are
      among the strongest of all known human polyomaviruses in 10 different cell lines.
AB  - Recently, 11 new human polyomaviruses (HPyVs) have been isolated and named KI,
      WU, Merkel cell polyomavirus (MCPyV), HPyV6,  -7,  -9,  -10 and  -12,
      Trichodysplasia spinulosa-associated polyomavirus (TSPyV), STLPyV and NJPyV-2013.
      Little is known about cell tropism of the novel HPyVs, and cell cultures allowing
      virus propagation are lacking. Because viral tropism partially depends on the
      interaction of cellular transcription factors with the viral promoter, we
      monitored the promoter activity of all known HPyVs. Therefore, we compared the
      relative early and late promoter activity of the BK polyomavirus (BKPyV) (WW
      strain) with the corresponding activities of the other HPyVs in 10 different cell
      lines derived from brain, colon, kidney, liver, lung, the oral cavity and skin.
      Our results show that the BKPyV, MCPyV, TSPyV and HPyV12 early promoters
      displayed the strongest activity in most cell lines tested, while the remaining
      HPyV had relative low early promoter activity. HPyV12 showed the highest late
      promoter activity of all HPyVs in most cell lines, but also the BKPyV, MCPyV and
      TSPyV late promoters belonged to the stronger ones among HPyVs. The HPyVs with
      weak early promoter activity had in general also weak late promoter activity,
      except for HPyV10 whose late promoter was relatively strong in six of the 10 cell
      lines. A 20 bp deletion in the promoter of an HPyV12 variant significantly
      affected both early and late promoter activity in most cell lines. In conclusion,
      our findings suggest which cell lines may be suitable for virus propagation and
      may give an indication of the cell tropism of the HPyVs.

PMID- 25968128
TI  - Pathogenic pathways are activated in each major cell type of the glomerulus in
      the Cd2ap mutant mouse model of focal segmental glomerulosclerosis.
AB  - BACKGROUND: Mutations in several genes expressed in podocytes, including Cd2ap,
      have been associated with focal segmental glomerulosclerosis in humans. Mutant
      mouse models provide an opportunity to better understand the molecular pathology
      that drives these diseases. METHODS: In this report we use a battery of
      transgenic-GFP mice to facilitate the purification of all three major cell types
      of the glomerulus from Cd2ap mutant mice. Both microarrays and RNA-seq were used
      to characterize the gene expression profiles of the podocytes, mesangial cells
      and endothelial cells, providing a global dual platform cross-validating dataset.
      RESULTS: The mesangial cells showed increased expression of profibrotic factors,
      including thrombospondin, Tgfb2 and Tgfb3, as well as the angiogenesis factor
      Vegf. They also showed upregulation of protective genes, including Aldh1a2,
      involved in retinoic acid synthesis and Decorin, a Tgfb antagonist. Of interest,
      the mesangial cells also showed significant expression of Wt1, which has
      generally been considered podocyte specific. The Cd2ap mutant podocytes showed
      upregulation of proteases as well as genes involved in muscle and vasculature
      development and showed a very strong gene expression signature indicating
      programmed cell death. Endothelial cells showed increased expression of the
      leukocyte adhesion associated factors Vcam1 and Sele, as well as Midkine
      (promoting angiogenesis), endothelin and many genes responsive to cytokines and
      interferons. CONCLUSIONS: This study provides a comprehensive analysis of the
      changing properties of the three cell types of the glomerulus in Cd2ap mutants,
      identifying activated and repressed pathways and responsible genes, thereby
      delivering a deeper molecular understanding of this genetic disease.

PMID- 25968130
TI  - Megabirnavirus structure reveals a putative 120-subunit capsid formed by
      asymmetrical dimers with distinctive large protrusions.
AB  - Rosellinia necatrix megabirnavirus 1 (RnMBV1) W779 is a bi-segmented dsRNA virus
      and a strain of the type species Rosellinia necatrix megabirnavirus 1 of the
      family Megabirnaviridae. RnMBV1 causes severe reduction of both mycelial growth
      of Rosellinia necatrix in synthetic medium and fungal virulence to plant hosts,
      and thus has strong potential for virocontrol (biological control using viruses)
      of white rot. The structure of RnMBV1 was examined by cryo-electron microscopy
      and three-dimensional reconstruction at 15.7 A resolution. The diameter of the
      RnMBV1 capsid was 520 A, and the capsid was composed of 60 asymmetrical dimers in
      the T = 1 (so-called T = 2) lattice that is well conserved among dsRNA viruses.
      However, RnMBV1 has putatively 120 large protrusions with a width of ~ 45 A and a
      height of ~ 50 A on the virus surface, making it distinguishable from the other
      dsRNA viruses.

PMID- 25968131
TI  - Elective courses for medical students during the preclinical curriculum: a
      systematic review and evaluation.
AB  - OBJECTIVE: Preclinical medical student electives are prevalent at medical schools
      across the United States, but the range of electives available and their impact
      on medical student education are not well described in the literature. The
      objective of this article is to review the literature relating to preclinical
      medical student electives and their impact on medical student educational
      outcomes. METHODS: We reviewed studies that met the following criteria: English
      language articles describing preclinical US-based medical electives. We used
      PubMed journal databases and limited our search for the time period 1999-2014. We
      excluded electives based in other countries or electives designed for third or
      fourth year students. Data abstracted included the topic of the elective,
      qualitative descriptions of the electives, and any associated surveys or exam
      data associated with the electives. Data were synthesized using descriptive
      tables sorting electives by broad topic. Reported outcomes and statistical
      methods were analyzed to assess study quality. RESULTS: We found a wide range of
      subjects taught in the form of preclinical medical school electives. We
      identified electives in clinical skills, the humanities, student lifestyle,
      specialty-specific electives, and an assortment of other miscellaneous electives.
      Surveys and exams administered to students showed that the electives were
      universally well received by students. Of the 37 electives identified, 15
      electives used quantitative objective assessments, such as knowledge exams, while
      the remaining tended to use student self-reported results. CONCLUSIONS:
      Preclinical medical student electives are prevalent at medical schools across the
      United States and have a significant impact on medical student education.

PMID- 25968132
TI  - Determinants of patient satisfaction and function related to vision following
      cataract surgery in eyes with no visually consequential ocular co-morbidity.
AB  - PURPOSE: To investigate subjectively reported outcomes following cataract surgery
      and the relationships between such outcomes in the context of falling thresholds
      for cataract surgery. SETTING: Large, private, non-refractive cataract practice,
      Institute of Eye Surgery, Whitfield Clinic, Waterford, Ireland METHODS: Pre
      operative, intra-operative and post-operative data of 2552 eyes undergoing
      phacoemulsification and implantation of the Tecnis(R) ZCB00 1-piece intraocular
      lens (IOL) by a single surgeon between July 2009 and October 2013 was analysed.
      Patients without visually consequential ocular co-morbidity completed two
      validated questionnaires, designed to assess subjectively perceived visual
      functioning and identify symptoms of dysphotopsia following cataract surgery.
      RESULTS: 54.8 % of questionnaire respondents were entirely satisfied
      (satisfaction 10/10) post-operatively, with 83.7 % reporting satisfaction of
      >=7/10. Satisfaction was positively associated with patient age and negatively
      associated with spectacle dependence, dysphotopsia, and function related to
      vision (NEI VF-11) score. The mean (+/-standard deviation[SD]) dysphotopsia score
      was 1.36 (+/-1.9; scale 0-10), with 40 % of respondents reporting no dysphotopsia
      symptoms and 9.8 % reporting clinically meaningful dysphotopsia. The mean (+/-SD)
      National Eye Institute visual function-11 (NEI VF-11) score was 0.33 (+/-0.53;
      scale 0-4) and reduced function related to vision was associated with increasing
      severity of dysphotopsia symptoms. When linear regression was applied, 17.5 % of
      the variation in functionality was attributable to symptoms of dysphotopsia.
      CONCLUSION: Dysphotopsia is an important determinant of a patient having
      difficulty with vision-related tasks following cataract surgery, and patient
      satisfaction is positively associated with patient age and negatively associated
      with spectacle in dependence, dysphotopsia and function related to the vision
      (NEI VF-11) score.

PMID- 25968133
TI  - The hidden practices and experiences of healthcare practitioners dealing with
      fuel poverty.
AB  - BACKGROUND: Fuel poverty negatively impacts a population's health affecting life
      chances along the life course. Moreover, it represents a substantial inequality
      in the UK. Healthcare practitioners (HCPs) have a key role in identifying and
      supporting patients who are fuel poor. METHODS: A qualitative inquiry with
      District Nurses and General Practitioners, to explore their understanding and
      experiences of dealing with patients living in fuel poverty. RESULTS:
      Participants recognize fuel poverty by observing material cues. They perceive
      their relationship with the patient as pivotal to recognizing the fuel poor.
      Practitioners' sense of responsibility for their patients' social concerns is
      determined by their knowledge about the link to health outcomes. The services
      that they sign-post to are motivated by their experience dealing with the
      service, or their patients' experiences of the service. CONCLUSION: Participants'
      reliance on temporary material cues resulted in few experiences of recognition of
      the fuel poor. HCPs' perceptions of patient pride and the lack of personal
      relationship between doctor and patient presented barriers to identifying fuel
      poor patients. A limitation of this study is the small sample size of nine
      participants. These came from two professional groups, which afforded more depth
      of exploration, but may limit applicability to other professionals.

PMID- 25968134
TI  - Geographic variation and socio-demographic determinants of the co-occurrence of
      risky health behaviours in 27 European Union member states.
AB  - BACKGROUND: Risky health behaviours such as tobacco and alcohol abuse, physical
      inactivity and poor diet may play an important role in disease development. The
      aim of the present study was to assess the geographical distribution and socio
      demographic determinants of risky health-related behaviours in 27 member states
      (MSs) of the European Union (EU). METHODS: Data from the 2009 Eurobarometer
      survey (wave 72.3; n = 26 788) were analysed. Tobacco use, alcohol consumption,
      physical activity and fruit consumption were assessed through a self-reported
      questionnaire provided to participants from 27 EU MSs. Within the analyses,
      participants with three or more lifestyle risk factors were classified as
      individuals with co-occurrence of risk factors. RESULTS: Among respondents aged
      15 or older, 28.2% had none of the aforementioned behavioural risk factors,
      whereas 9.9% had three or more lifestyle risk factors. Males [adjusted odds ratio
      (aOR) = 2.50; 95% confidence interval (95% CI): 2.17-2.88] and respondents of
      middle (aOR = 1.60; 95% CI: 1.36-1.89) or lower income (aOR = 2.63; 95% CI: 2.12
      3.26) were more likely to report co-occurrence of behavioural risk factors, as
      well as respondents in Northern (aOR = 1.43; 95% CI: 1.14-1.78), Western (aOR =
      1.28; 95% CI: 1.06-1.56) and Eastern Europe (aOR = 1.28; 95% CI: 1.06-1.55), when
      compared with Southern European respondents. CONCLUSIONS: The above analyses
      indicate significant geographical and social variation in the distribution of the
      co-occurrence of behavioural risk factors for disease development.

PMID- 25968135
TI  - Pre-clinical In Vitro and In Vivo Models for Heart Valve Therapies.
AB  - Heart valve disease is a frequently encountered pathology, related to high
      morbidity and mortality rates. Animal models are interesting to investigate the
      causality but also underlying mechanisms and potential treatments of human heart
      valve diseases. Strongly believing that both in vivo and ex vivo models are
      fundamental to support research and development of new technologies, we here
      report some examples of heart valve disease models, which in our experience have
      been actively used to support the development of new valve therapies. 

PMID- 25968136
TI  - Transcriptional Signatures, Imaging, and Coronary Artery Disease Diagnosis.

PMID- 25968137
TI  - Views That Are Shared With Others Are Expressed With Greater Confidence and
      Greater Fluency Independent of Any Social Influence.
AB  - Research on group influence has yielded a prototypical majority effect (PME):
      Majority views are endorsed faster and with greater confidence than minority
      views, with the difference increasing with majority size. The PME was attributed
      to conformity pressure enhancing confidence in consensual views and causing
      inhibition in venturing deviant opinions. Our results, however, indicate that PME
      for binary choices can arise from the process underlying confidence and latency
      independent of social influence. PME was demonstrated for tasks and conditions
      that are stripped of social relevance; it was observed in within-individual
      analyses in contrasting the individual's more frequent and less frequent
      responses to the same item, and was found for the predictions of others'
      responses. A self-consistency model, which assumes that choice and confidence are
      based on the sampling of representations from a commonly shared pool of
      representations, yielded a PME for confidence and latency. Behavioral
      implications of the results are discussed. 

PMID- 25968138
TI  - The Incremental Validity of Narrative Identity in Predicting Well-Being: A Review
      of the Field and Recommendations for the Future.
AB  - Grounded in four theoretical positions-structural, cognitive, phenomenological,
      and ethical-the present review demonstrates the empirical evidence for the
      incremental validity of narrative identity as a cross-sectional indicator and
      prospective predictor of well-being, compared with other individual difference
      and situational variables. In doing so, we develop an organizational framework of
      four categories of narrative variables: (a) motivational themes, (b) affective
      themes, (c) themes of integrative meaning, and (d) structural elements. Using
      this framework, we detail empirical evidence supporting the incremental
      association between narrative identity and well-being, a case that is strongest
      for motivational, affective, and integrative meaning themes. These categories of
      themes serve as vital complimentary correlates and predictors of well-being,
      alongside commonly assessed variables such as dispositional personality traits.
      We then use the theoretically grounded review of the empirical literature to
      develop concrete areas of future research for the field. 

PMID- 25968139
TI  - Fisheries Closed Areas Strengthen Scallop Larval Settlement and Connectivity
      Among Closed Areas and Across International Open Fishing Grounds: A Model Study.
AB  - This study examined whether a measured increase in average body size of adult sea
      scallops inside three fishery closed areas on Georges Bank (GB), United States
      (US), was sufficient to increase larval supply to closed areas and open fishing
      areas in both US and Canadian areas of the Bank. The effects of adult scallop
      density-at-size and fecundity-at-size on egg production were compared among open
      and closed fishery areas, countries, and time periods before and after the closed
      areas were established. Estimated egg production was then used to define spawning
      conditions in a coupled biological-physical larval tracking model that simulated
      larval development, mortality, and dispersal. Results showed that order of
      magnitude increases in larval settlement after closure were facilitated by
      increases in size-dependant egg production inside and dispersal from Closed Areas
      I and II, but not Nantucket Lightship Closed Area. The distributions of both egg
      production and larval settlement became more uniform across the Bank, causing the
      relative contribution of Canadian larvae to US scallop aggregations to decrease
      after establishment of Closed Areas I and II. Decreases in small and medium-sized
      scallop density in Canada and decreases in large scallops over the US-Southern
      Flank after closure caused local declines in egg production but were not
      sufficient to negatively affect larval settlement at the regional scale. Our
      model suggests that the establishment of fishery closed areas on GB considerably
      strengthened larval supply and settlement within and among several adult scallop
      aggregations.

PMID- 25968140
TI  - A Critical Assessment of the Ecological Assumptions Underpinning Compensatory
      Mitigation of Salmon-Derived Nutrients.
AB  - We critically evaluate some of the key ecological assumptions underpinning the
      use of nutrient replacement as a means of recovering salmon populations and a
      range of other organisms thought to be linked to productive salmon runs. These
      assumptions include: (1) nutrient mitigation mimics the ecological roles of
      salmon, (2) mitigation is needed to replace salmon-derived nutrients and
      stimulate primary and invertebrate production in streams, and (3) food resources
      in rearing habitats limit populations of salmon and resident fishes. First, we
      call into question assumption one because an array of evidence points to the
      multi-faceted role played by spawning salmon, including disturbance via redd
      building, nutrient recycling by live fish, and consumption by terrestrial
      consumers. Second, we show that assumption two may require qualification based
      upon a more complete understanding of nutrient cycling and productivity in
      streams. Third, we evaluate the empirical evidence supporting food limitation of
      fish populations and conclude it has been only weakly tested. On the basis of
      this assessment, we urge caution in the application of nutrient mitigation as a
      management tool. Although applications of nutrients and other materials intended
      to mitigate for lost or diminished runs of Pacific salmon may trigger ecological
      responses within treated ecosystems, contributions of these activities toward
      actual mitigation may be limited. 

PMID- 25968142
TI  - Ethical reasons for narrowing the scope of biotech patents.
AB  - Patents on biotech products have a scope that goes well beyond what is covered by
      the most widely applied ethical justifications of intellectual property. Neither
      natural rights theory from Locke, nor public interest theory of IP rights
      justifies the wide scope of legal protection. The article takes human genes as an
      example, focusing on the component that is not invented but persists as unaltered
      gene information even in the synthetically produced complementary DNA, the cDNA.
      It is argued that patent on cDNA holds this information captive, or
      illegitimately appropriates it in limiting other researchers and inventors'
      opportunity to explore new functions and uses based on this non-invented
      information. A tighter connection between legal IP protection and the use
      description stated in the patent claim is suggested. By binding protection to the
      product's foreseeable functions and use, instead of the product itself and all
      future uses of it, legitimacy of biotech product patents is restored. 

PMID- 25968141
TI  - Stress-mediated progression of solid tumors: effect of mechanical stress on
      tissue oxygenation, cancer cell proliferation, and drug delivery.
AB  - Oxygen supply plays a central role in cancer cell proliferation. While vascular
      density increases at the early stages of carcinogenesis, mechanical solid
      stresses developed during growth compress tumor blood vessels and, thus,
      drastically reduce not only the supply of oxygen, but also the delivery of drugs
      at inner tumor regions. Among other effects, hypoxia and reduced drug delivery
      compromise the efficacy of radiation and chemo/nanotherapy, respectively. In the
      present study, we developed a mathematical model of tumor growth to investigate
      the interconnections among tumor oxygenation that supports cancer cell
      proliferation, the heterogeneous accumulation of mechanical stresses owing to
      tumor growth, the non-uniform compression of intratumoral blood vessels due to
      the mechanical stresses, and the insufficient delivery of oxygen and therapeutic
      agents because of vessel compression. We found that the high vascular density and
      increased cancer cell proliferation often observed in the periphery compared to
      the interior of a tumor can be attributed to heterogeneous solid stress
      accumulation. Highly vascularized peripheral regions are also associated with
      greater oxygenation compared with the compressed, less vascularized inner
      regions. We also modeled the delivery of drugs of two distinct sizes, namely
      chemotherapy and nanomedicine. Model predictions suggest that drug delivery is
      affected negatively by vessel compression independently of the size of the
      therapeutic agent. Finally, we demonstrated the applicability of our model to
      actual geometries, employing a breast tumor model derived from MR images. 

PMID- 25968144
TI  - Histopathological changes in rat pancreas and skeletal muscle associated with
      high fat diet induced insulin resistance.
AB  - The effects of a high fat diet on the development of diabetes mellitus, insulin
      resistance and secretion have been widely investigated. We investigated the
      effects of a high fat diet on the pancreas and skeletal muscle of normal rats to
      explore diet-induced insulin resistance mechanisms. Forty-four male Wistar rats
      were divided into six groups: a control group fed standard chow, a group fed a
      45% fat diet and a group fed a 60% fat diet for 3 weeks to measure acute effects;
      an additional three groups were fed the same diet regimens for 8 weeks to measure
      chronic effects. The morphological effects of the two high fat diets were
      examined by light microscopy. Insulin in pancreatic islets was detected using
      immunohistochemistry. The homeostasis model assessment of insulin resistance
      index and insulin staining intensity in islets increased significantly with acute
      administration of high fat diets, whereas staining intensity decreased with
      chronic administration of the 45% fat diet. Islet areas increased significantly
      with chronic administration. High fat diet administration led to islet
      degeneration, interlobular adipocyte accumulation and vacuolization in the
      pancreatic tissue, as well as degeneration and lipid droplet accumulation in the
      skeletal muscle tissue. Vacuolization in the pancreas and lipid droplets in
      skeletal muscle tissue increased significantly with chronic high fat diet
      administration. We suggest that the glucolipotoxic effects of high fat diet
      administration depend on the ratio of saturated to unsaturated fatty acid content
      in the diet and to the total fat content of the diet. 

PMID- 25968143
TI  - FUS regulates AMPA receptor function and FTLD/ALS-associated behaviour via GluA1
      mRNA stabilization.
AB  - FUS is an RNA/DNA-binding protein involved in multiple steps of gene expression
      and is associated with amyotrophic lateral sclerosis (ALS) and fronto-temporal
      lobar degeneration (FTLD). However, the specific disease-causing and/or modifying
      mechanism mediated by FUS is largely unknown. Here we evaluate intrinsic roles of
      FUS on synaptic functions and animal behaviours. We find that FUS depletion
      downregulates GluA1, a subunit of AMPA receptor. FUS binds GluA1 mRNA in the
      vicinity of the 3' terminus and controls poly (A) tail maintenance, thus
      regulating stability. GluA1 reduction upon FUS knockdown reduces miniature EPSC
      amplitude both in cultured neurons and in vivo. FUS knockdown in hippocampus
      attenuates dendritic spine maturation and causes behavioural aberrations
      including hyperactivity, disinhibition and social interaction defects, which are
      partly ameliorated by GluA1 reintroduction. These results highlight the pivotal
      role of FUS in regulating GluA1 mRNA stability, post-synaptic function and FTLD
      like animal behaviours. 

PMID- 25968145
TI  - A stereological and histopathological study of the effects of exposure of male
      rat testes to mercury vapor.
AB  - Mercury is ubiquitous in the environment; it is an occupational pollutant and a
      potential toxicant. We investigated the effects of exposure of rat testes to
      mercury vapor (Hg(0)). Twelve male rats were divided into two groups of six: the
      rats of the Hg(0) group were exposed to mercury (1 mg/m(3)/day) in a chamber for
      six weeks; the control group rats were housed under the same conditions without
      exposure to Hg(0). After the experimental period, the testes were removed,
      sections of testis were evaluated histopathologically after hematoxylin and eosin
      staining, and stereologically using the Cavalieri principle and optical
      fractionator methods. We found significant decreases in the total volume of
      testis, diameters of seminiferous tubules and total volume of seminiferous
      tubules. Significant decreases were detected in the numbers of Sertoli cells,
      spermatogonia, spermatocytes and spermatids of the Hg(0) group compared to the
      control group. In the Hg(0) exposed group, spermatogenic cells were degenerated
      and seminiferous tubules were atrophied. 

PMID- 25968146
TI  - Porcine placental immunoexpression of vascular endothelial growth factor,
      placenta growth factor, Flt-1 and Flk-1.
AB  - Porcine embryo mortalities cause economic losses. Development of the placental
      vascular bed is required for successful gestation and postnatal survival. We
      studied the temporal and spatial distributions of vascular endothelial growth
      factor (VEGF), placenta growth factor (PlGF) and their receptors, Flt-1 and Flk
      1. We used crossbred swine placental tissues from 30, 60, 80, 90 and 114 (term)
      days of gestation. Both VEGF and PlGF were present during gestation. At early
      pregnancy and at term, VEGF probably acts through Flt-1; during intermediate
      periods, its function is mediated by Flk-1. By day 90, factors other than members
      of VEGF family appear to be involved. 

PMID- 25968147
TI  - Editorial: a new shift in the paradigm of treatment for the irritable bowel
      syndrome?

PMID- 25968148
TI  - Editorial: spontaneous bacterial peritonitis--bacteriology, diagnosis, treatment,
      risk factors and prevention.

PMID- 25968149
TI  - Editorial: spontaneous bacterial peritonitis--bacteriology, diagnosis, treatment,
      risk factors and prevention. Authors' reply.

PMID- 25968150
TI  - Editorial: differentiating chronic idiopathic constipation from constipation
      predominant irritable bowel syndrome--possible and important?

PMID- 25968151
TI  - Editorial: differentiating chronic idiopathic constipation from constipation
      predominant irritable bowel syndrome--possible and important?--Authors' reply.

PMID- 25968152
TI  - Letter: systemic therapy for psoriasis could affect the prevalence of NAFLD.

PMID- 25968153
TI  - Letter: tumour necrosis factor alpha blocker switching--a not so simple
      pharmacokinetic.

PMID- 25968154
TI  - Letter: tumour necrosis factor alpha blocker switching--a not so simple
      pharmacokinetic. Authors' reply.

PMID- 25968155
TI  - Letter: low muscle mass and disordered eating as causes of osteopenia in
      inflammatory bowel disease.

PMID- 25968156
TI  - Letter: low muscle mass and disordered eating as causes of osteopenia in
      inflammatory bowel disease--authors' reply.

PMID- 25968157
TI  - Role of verapamil in preventing and treating hypertrophic scars and keloids.
AB  - Keloid and hypertrophic scars are difficult to manage and remain a therapeutic
      challenge. Verapamil has shown a great potential in the management of keloid and
      hypertrophic scars. Comparing with conventional corticosteroid injections,
      verapamil could improve the appearance of keloid and hypertrophic scars, and is
      associated with a lower incidence of adverse effects. Is verapamil an effective
      alternative modality in the prevention and treatment of keloid and hypertrophic
      scars? The aim of this study was to assess the effectiveness of verapamil in
      preventing and treating keloid and hypertrophic scars. Searches were conducted in
      Medline, EMbase and Cochrane databases from 1974 to January 2015. The selection
      of articles was limited to human subjects. Five randomised controlled trials
      (RCTs) or cluster-randomised trials or controlled clinical trials (CCTs)
      comparing the efficacy of verapamil with conventional treatments were identified.
      The results showed that verapamil could improve keloid and hypertrophic scars,
      and was not significantly different from conventional corticosteroid injections.
      Few adverse effects were observed. However, this result should be considered
      carefully, as most of the included studies have a high risk of bias because of
      issues with randomization, allocation concealment, blinding, incomplete outcomes
      and selective reporting. In conclusion, verapamil could act as an effective
      alternative modality in the prevention and treatment of keloid and hypertrophic
      scars. More high-quality, multiple-centre, large-sample (RCTs) are required to
      define the role of verapamil in preventing and treating keloid and hypertrophic
      scars. 

PMID- 25968158
TI  - Mitochondrial tRNA(Ser(UCN)) variants in 2651 Han Chinese subjects with hearing
      loss.
AB  - Mutations in the mitochondrial DNA have been associated with hearing loss.
      However, the prevalence and spectrum of mitochondrial tRNA mutations in hearing
      impaired subjects are poorly understood. In this report, we have investigated the
      prevalence and spectrum of mitochondrial tRNA(Ser(UCN)) mutations in a large
      cohort of 2651 Han Chinese subjects with hearing loss. The clinical evaluation
      showed that 744 subjects (432 males and 312 females) had a history of exposure to
      aminoglycosides and other probands exhibited nonsyndromic hearing loss.
      Mutational analysis of tRNA(Ser(UCN)) gene identified 9 (8 known and 1 novel)
      variants. The prevalence of the known deafness-associated 7511T>C, 7505T>C and
      7445A>C mutations was 0.04%, 0.04% and 0.04%, respectively. Other variants were
      evaluated by the evolutionary conservation, allelic frequency of Chinese
      controls, potential structural and functional alterations and pedigree analysis.
      Three variants were polymorphisms, while the 7444G>A, 7471DelG and 7496A>G
      variants were putative deafness-associated mutations. These putative deafness
      associated variants accounted for 0.68% cases of hearing-impaired subjects in
      this cohort. The low penetrance of hearing loss in pedigrees carrying one of
      these putative deafness-associated mutations indicated that the mutation(s) is
      necessary but itself insufficient to produce a clinical phenotype. Other genetic
      or environmental factor(s) may influence the phenotypic manifestation of these
      tRNA(Ser(UCN)) mutations. Moreover, mtDNAs in 20 probands carrying one of the
      putative deafness-associated mutations were widely dispersed among 8 Eastern
      Asian haplogroups. In particular, the occurrences of haplogroups D4a, M22, and H2
      in patients carrying the deafness-associated variants were higher than those in
      Chinese controls. These data further support that the mitochondrial
      tRNA(Ser(UCN)) gene is the hot spot for mutations associated with hearing loss.
      Thus, our findings may provide valuable information for the further understanding
      of pathophysiology and management of hearing loss.

PMID- 25968160
TI  - Ag2 and Ag3 clusters: synthesis, characterization, and interaction with DNA.
AB  - Subnanometric samples, containing exclusively Ag2 and Ag3 clusters, were
      synthesized for the first time by kinetic control using an electrochemical
      technique without the use of surfactants or capping agents. By combination of
      thermodynamic and kinetic measurements and theoretical calculations, we show
      herein that Ag3 clusters interact with DNA through intercalation, inducing
      significant structural distortion to the DNA. The lifetime of Ag3 clusters in the
      intercalated position is two to three orders of magnitude longer than for
      classical organic intercalators, such as ethidium bromide or proflavine. 

PMID- 25968161
TI  - Nanoliposomes: Synthesis methods and applications in cosmetics.
AB  - Nanotechnology is used frequently in marketing skin care goods, and whereas the
      word sounds as if it belongs in robotics and science fiction, it is rapidly
      becoming common in medicine and skin care. As few people actually recognize what
      the technology, benefits, or possible implications of its use are, we determined
      to outline them. The type of nanotechnology that is most significant in
      cosmetics, skin care and health products is the use of nanoparticles (or Bucky
      balls as they are known in manufacturing), and a particular kind of these
      nanoparticles have been touted as the next generation of liposomes. Nanoliposomes
      is one of the most recognized names for the nanoparticles used in skin care and
      cosmetic products, and we are also familiar with the term liposome, so this
      connection between the two is the perhaps the best way to clarify what
      nanoliposomes are. In this article, some of the techniques for their production
      are reviewed. Common methods of nanoliposome preparation are discussed. 

PMID- 25968162
TI  - Evaluation of safety and efficacy of 980-nm diode laser-assisted lipolysis versus
      traditional liposuction for submental rejuvenation: A randomized clinical trial.
AB  - BACKGROUND: Submental fat accumulation and skin laxity is a frequent concern of
      cosmetic patients. OBJECTIVE: The aim of this randomized prospective controlled
      clinical trial was to compare the efficacy and safety of laser-assisted lipolysis
      and liposuction in the submental rejuvenation. MATERIAL AND METHODS: Thirty-six
      female adults were enrolled in this clinical trial and were categorized into two
      groups: group 1 underwent 980-nm diode laser with the power of 6-8 W and group 2
      underwent traditional liposuction. Patients were evaluated with ultrasonography 2
      weeks and 2 months after the procedures. RESULTS: Ultrasonographic evaluation
      reported the significant reduction of fat thickness in each group compared with
      the baseline (p value < 0.001). At the 2 weeks and 2 months follow-up visit, fat
      thickness reduction was significantly higher in the lipolysis group (p value <
      0.05). Overall patients' satisfaction in lipolysis group was higher than
      liposuction with 11 (61%) of lipolysis patients being very satisfied in contrast
      to 10 (55.5%) of liposuction patients reporting "dissatisfied or neutral"
      results. CONCLUSION: Laser-assisted lipolysis using 980-nm diode is approved to
      be safe and effective for skin tightening and rejuvenation of the submental area
      and seems to be a better option than traditional techniques for treatment of this
      cosmetic problem.

PMID- 25968159
TI  - Fluorophores, environments, and quantification techniques in the analysis of
      transmembrane helix interaction using FRET.
AB  - Forster resonance energy transfer (FRET) has been widely used as a spectroscopic
      tool in vitro to study the interactions between transmembrane (TM) helices in
      detergent and lipid environments. This technique has been instrumental to many
      studies that have greatly contributed to quantitative understanding of the
      physical principles that govern helix-helix interactions in the membrane. These
      studies have also improved our understanding of the biological role of
      oligomerization in membrane proteins. In this review, we focus on the
      combinations of fluorophores used, the membrane mimetic environments, and
      measurement techniques that have been applied to study model systems as well as
      biological oligomeric complexes in vitro. We highlight the different formalisms
      used to calculate FRET efficiency and the challenges associated with accurate
      quantification. The goal is to provide the reader with a comparative summary of
      the relevant literature for planning and designing FRET experiments aimed at
      measuring TM helix-helix associations.

PMID- 25968163
TI  - Anetoderma treated with combined 595-nm pulsed-dye laser and 1550-nm non-ablative
      fractionated laser.
AB  - Anetoderma is a skin disorder characterized by a focal loss of dermal elastic
      tissue whereby patients present with soft, depressible lesions. We postulated
      that a series of combination treatment using the 595-nm pulsed dye laser (PDL)
      and the 1550-nm non-ablative fractionated laser (NAFL) would improve the
      anetoderma lesions. Our patient with biopsy proven anetoderma received 3
      treatments with a combination of 595-nm PDL and 1550-nm NAFL spaced 3 weeks
      apart. Skin biopsies were performed at baseline and immediately prior to the
      third treatment. Stains for hematoxylin and eosin and Verhoeff Van Gieson (VVG)
      were performed. Improvement in lesion color, texture, and overall appearance was
      noted after the second treatment and continued following the third treatment.
      Post-treatment VVG staining demonstrated an increase in dermal elastin fibers and
      a decrease in elastin fiber fragmentation. Thus, the combination of 595-nm PDL
      and 1550-nm NAFL should be considered as a treatment modality for anetoderma. 

PMID- 25968164
TI  - Impact of pigmentary disorders on quality of life in Japan: Interest of the
      BeautyQoL instrument.
AB  - Skin pigmentary disorders and uneven skin tone represent common cosmetic concerns
      in Japan where fairer skin is culturally desirable. As the demographics of Asian
      countries continue to evolve, there is a need to understand the impact of
      cosmetic skin concerns on quality of life (QoL). 199 Japanese women self-claiming
      facial skin pigmentation disorders were asked to complete the BeautyQoL
      questionnaire, and the results were compared with those of a control group of 200
      women. Of the five dimensions of the BeautyQoL questionnaire, the dimension
      "mood" appeared to be significantly lower in the group presenting facial dark
      spots, as compared with the control group (p < 0.05). In the group presenting
      facial dark spots, the five dimensions and the global score showed that subjects
      concerned had lower scores than subjects less concerned, even if statistical
      significance was not reached. This study confirms that common pigmentary
      disorders such as facial black spots may negatively impact QoL. Further
      comparative studies with a controlled randomized design would be necessary to
      confirm these findings. 

PMID- 25968165
TI  - Hair follicles are viable after delayed FUE procedure.
AB  - Nowadays, male pattern hair loss is usually managed with hair transplant.
      However, maintaining the hair follicle viability between extraction and
      implantation period is a great concern which restricts the hair transplantation
      period. However, it is possible that the hair follicles can be preserved and be
      viable for few days. Here, we report a case with delayed follicular unit
      extraction in three consecutive days with acceptable hair growth after a 5-month
      follow-up. 

PMID- 25968166
TI  - A randomized, split-face clinical trial of Q-switched alexandrite laser versus Q
      switched Nd:YAG laser in the treatment of bilateral nevus of Ota.
AB  - Different types of Q-switched (QS) lasers have been used successfully to treat
      nevus of Ota. The purpose of this study was to compare the clinical efficacy and
      complication of QS alexandrite (QS Alex) laser versus QS neodymium:yttrium
      aluminum garnet (Nd:YAG) (QS Nd:YAG) laser for bilateral nevus of Ota. Seventeen
      patients with bilateral nevus of Ota were treated randomly with QS Alex in one
      half of face and QS Nd:YAG in the other half with an interval of at least 3
      months between each. Subjective assessment was made by both patients and
      dermatologists. Patients were also examined for evidence of complications. All
      patients experienced improvement (p < 0.05). There was no statistically
      significant difference between the two sides (p > 0.05). The pain after a short
      period of laser therapy was more severe for QS Alex than for QS Nd:YAG laser.
      Vesicles developed in 1 patient after QS Alex therapy. Both QS Alex laser and QS
      Nd:YAG laser were equally effective at improving bilateral nevus of Ota. Patients
      tolerate QS Nd:YAG laser better than QS Alex laser. 

PMID- 25968167
TI  - Evaluation of a new hyaluronic acid dermal filler for volume restoration.
AB  - OBJECTIVES: The present study aimed to evaluate the effectiveness and safety of
      hyaluronic acid gel for the treatment of volume loss or contour deficiency.
      METHODS: This 6-month, open-label study recruited sixty adults aged 40-65 years
      with bilateral moderate to severe volume loss or contour deficiency (Facial
      Volume Loss Scale [FVLS] score: 2-5). Eligible subjects were treated at the
      baseline visit with an injection of hyaluronic acid gel in one or more of three
      facial subregions: the zygomatic malar region, the anteromedial cheek and
      nasolabial folds. RESULTS: A significant improvement from baseline was observed
      in the FVLS score at each study visit up to 6 months post treatment (p < 0.0125
      by Wilcoxon test). A significant improvement was also observed in the Global
      Aesthetic Improvement Scale (GAIS) at each visit up to 6 months. The study showed
      that the GAIS score improved in 100% of subjects at month 3, while at the end of
      the study (month 6) the percentage of improved subjects decreased to 91.
      Treatment effect was maintained by 100% of subjects up to month 3, while 57% of
      subjects showed a persistence of effect up to month 6. CONCLUSIONS: Volume loss
      or contour deficiency may be safely and effectively corrected using the new
      dermal filler.

PMID- 25968168
TI  - A novel non-invasive radiofrequency dermal heating device for skin tightening of
      the face and neck.
AB  - BACKGROUND: Loose, lax skin is a common cosmetic complaint. Previous non-invasive
      skin tightening devices had modest efficacy and were associated with pain or
      downtime. New technologies may allow for effective skin tightening with a series
      of radiofrequency (RF) treatments with no downtime. OBJECTIVE: To evaluate the
      efficacy and safety of a novel bipolar RF device for skin tightening. METHODS:
      Fifteen consecutive female patients were enrolled in the case series; 14
      completed the study and were included in the analysis. The device under
      investigation is a novel, bipolar RF device allowing for achievement and
      maintenance of optimal dermal temperatures to stimulate collagen remodeling and
      skin tightening. Patients underwent a series of 4-6 weekly treatments. Three
      blinded, experienced cosmetic physicians evaluated paired pre-treatment and post
      treatment photographs and determined the associated improvement, if any. RESULTS:
      All patients (14/14) were determined to have a clinical improvement, as the pre
      treatment and post-treatment photographs were correctly identified by the
      evaluators. It was observed that 21% (3/14) of patients had significant
      improvement, 50% (7/14) had moderate improvement, and 29% (4/14) had mild
      improvement. No pain, side effects, or adverse events were observed. CONCLUSIONS:
      This novel bipolar RF device represents a safe, effective treatment option for
      non-invasive skin tightening.

PMID- 25968170
TI  - Welcome from the president.

PMID- 25968169
TI  - An update on cutaneous aging treatment using herbs.
AB  - Skin aging is caused by several factors. Ultraviolet (UV) exposure as well as
      oxidative stress elevates inflammatory mediators causing degradation of the
      extracellular matrix, which is regarded as the major cause of skin wrinkles, one
      of the signs of aging. Topical applications of active ingredients protect against
      dermal photodamage and scavenge radicals that can delay skin aging. Matrix
      metalloproteinase inhibitors against degradation of collagen, elastin, and
      hyaluronan are the key strategy to combat cutaneous aging. In addition, active
      ingredients with the efficacy to enhance extracellular matrix production,
      including those with UV protection efficacy, play an important role in protecting
      the skin from aging. Naturally derived compounds for combating skin wrinkles are
      gaining more interest among the consumers as they are perceived to be milder,
      safer, and healthier. This article, therefore, briefly addresses the causes of
      skin aging and extensively summarizes on herbs appraisal for skin wrinkles
      treatment. Therefore, delaying aging of skin using the functional herbs would
      maintain the individual's appearance with high esthetic and psychosocial impacts.

PMID- 25968171
TI  - Waterloo.

PMID- 25968173
TI  - Cardiovascular disease incidence and survival: Are migrants always worse off?
AB  - Studies on cardiovascular disease (CVD) incidence and survival show varying
      results between different ethnic groups. Our aim was to add a new dimension by
      exploring the role of migrant status in combination with ethnic background on
      incidence of-and survival from-CVD and more specifically acute myocardial
      infarction (AMI) and stroke. We conducted a historically prospective cohort study
      comprising all newly-arrived migrants to Denmark between 1.1.1993 and 31.12.2010
      (n = 114,331), matched 1:6 to Danish-born by age and sex. CVD incidence was
      retrieved from the National Patient Registry and differences in incidence were
      assessed by Poisson regression and stratified by sex. Survival differences were
      assessed by Cox regression using all-cause and cause-specific mortality as
      outcome. Male refugees had significantly lower incidence of CVD (RR = 0.89; 95 %
      CI 0.85-0.93) and stroke (IRR = 0.62; 95 % CI 0.56-0.69) compared to Danish-born,
      but significantly higher incidence of AMI (IRR = 1.12; 95 % CI 1.02-1.24). Female
      refugees had similar rates of CVD and AMI, but significantly lower incidence of
      stroke (RR = 0.76; 95 % CI 0.67-0.85). Both male and female family-reunified
      immigrants had significantly lower incidence of CVD, AMI and stroke. All-cause
      and cause-specific survival after CVD, AMI and stroke was similar or
      significantly better for migrants compared to Danish-born, regardless of type of
      migrant (refugee vs. family-reunified) or country of origin. Refugees are
      disadvantaged in terms of some types of cardiovascular disease compared to Danish
      born. Family-reunified migrants on the other hand had lower rates of CVD. All
      migrants had better survival than Danish-born indicating that migrants may not
      always be disadvantaged in health.

PMID- 25968174
TI  - Alcohol consumption and risk of dementia up to 27 years later in a large,
      population-based sample: the HUNT study, Norway.
AB  - The relationship between alcohol consumption and dementia risk is unclear. This
      investigation estimates the association between alcohol consumption reported in a
      population-based study in the mid-1980s and the risk for dementia up to 27 years
      later. The entire adult population in one Norwegian county was invited to the
      Nord-Trondelag Health Study during 1984-1986 (HUNT1): 88 % participated. The
      sample used in this study includes HUNT1 participants born between 1905 and 1946
      who completed the questionnaire assessing alcohol consumption. A total of 40,435
      individuals, of whom 1084 have developed dementia, are included in the analysis
      adjusted for age, sex, years of education, hypertension, obesity, smoking, and
      symptoms of depression. When adjusting for age and sex, and compared to reporting
      consumption of alcohol 1-4 times during the last 14 days (drinking infrequently),
      both abstaining from alcohol and reporting consumption of alcohol five or more
      times (drinking frequently) were statistically significantly associated with
      increased dementia risk with hazard ratios of 1.30 (95 % CI 1.05-1.61) and 1.45
      (1.11-1.90), respectively. In the fully adjusted analysis, drinking alcohol
      frequently was still significantly associated with increased dementia risk with a
      hazard ratio of 1.40 (1.07-1.84). However, the association between dementia and
      abstaining from alcohol was no longer significant (1.15, 0.92-1.43). Equivalent
      results for Alzheimer's disease and vascular dementia indicated the same patterns
      of associations. When adjusting for other factors associated with dementia,
      frequent alcohol drinking, but not abstaining from alcohol, is associated with
      increased dementia risk compared to drinking alcohol infrequently.

PMID- 25968175
TI  - An epidemiological model for prediction of endometrial cancer risk in Europe.
AB  - Endometrial cancer (EC) is the fourth most frequent cancer in women in Europe,
      and as its incidence is increasing, prevention strategies gain further
      pertinence. Risk prediction models can be a useful tool for identifying women
      likely to benefit from targeted prevention measures. On the basis of data from
      201,811 women (mostly aged 30-65 years) including 855 incident EC cases from
      eight countries in the European Prospective Investigation into Cancer and
      Nutrition cohort, a model to predict EC was developed. A step-wise model
      selection process was used to select confirmed predictive epidemiologic risk
      factors. Piece-wise constant hazard rates in 5-year age-intervals were estimated
      in a cause-specific competing risks model, five-fold-cross-validation was applied
      for internal validation. Risk factors included in the risk prediction model were
      body-mass index (BMI), menopausal status, age at menarche and at menopause, oral
      contraceptive use, overall and by different BMI categories and overall duration
      of use, parity, age at first full-term pregnancy, duration of menopausal hormone
      therapy and smoking status (specific for pre, peri- and post-menopausal women).
      These variables improved the discriminating capacity to predict risk over 5 years
      from 71% for a model based on age alone to 77% (overall C statistic), and the
      model was well-calibrated (ratio of expected to observed cases = 0.99). Our model
      could be used for the identification of women at increased risk of EC in Western
      Europe. To achieve an EC-risk model with general validity, a large-scale cohort
      consortium approach would be needed to assess and adjust for population
      variation.

PMID- 25968176
TI  - Smoking-attributable mortality in American Indians: findings from the Strong
      Heart Study.
AB  - Cigarette smoking is the leading preventable cause of death worldwide. American
      Indians have the highest proportion of smoking in the United States. However, few
      studies have examined the impact of cigarette smoking on disease mortality in
      this ethnically important but traditionally understudied minority population.
      Here we estimated the association of cigarette smoking with cardiovascular
      disease (CVD), cancer and all-cause mortality in American Indians participating
      in the Strong Heart Study, a large community-based prospective cohort study
      comprising of 4549 American Indians (aged 45-74 years) followed for about 20
      years (1989-2008). Hazard ratio and population attributable risk (PAR) associated
      with cigarette smoking were estimated by Cox proportional hazard model, adjusting
      for sex, study site, age, educational level, alcohol consumption, physical
      activity, BMI, lipids, renal function, hypertension or diabetes status at
      baseline, and interaction between current smoker and study site. We found that
      current smoking was significantly associated with cancer mortality (HR 5.0, [1.9
      13.4]) in men, (HR 3.9 [1.6-9.7] in women) and all-cause mortality (HR 1.8, [1.2
      2.6] in men, HR 1.6, [1.1-2.4] in women). PAR for cancer and all-cause mortality
      in men were 41.0 and 18.4 %, respectively, whereas the corresponding numbers in
      women were 24.9 and 10.9 %, respectively. Current smoking also significantly
      increases the risk of CVD deaths in women (HR 2.2 [1.1, 4.4]), but not men (HR
      1.2 [0.6-2.4]). PAR for CVD mortality in women was 14.9 %. In summary, current
      smoking significantly increases the risk of CVD (in women), cancer and all-cause
      mortality in American Indians, independent of known risk factors. Culturally
      specific smoking cessation programs are urgently needed to reduce smoking-related
      premature deaths.

PMID- 25968177
TI  - Autism beyond diagnostic categories: characterization of autistic phenotypes in
      schizophrenia.
AB  - BACKGROUND: Behavioral phenotypical continua from health to disease suggest
      common underlying mechanisms with quantitative rather than qualitative
      differences. Until recently, autism spectrum disorders and schizophrenia were
      considered distinct nosologic entities. However, emerging evidence contributes to
      the blurring of symptomatic and genetic boundaries between these conditions. The
      present study aimed at quantifying behavioral phenotypes shared by autism
      spectrum disorders and schizophrenia to prepare the ground for biological pathway
      analyses. METHODS: Specific items of the Positive and Negative Syndrome Scale
      were employed and summed up to form a dimensional autism severity score (PAUSS).
      The score was created in a schizophrenia sample (N = 1156) and validated in adult
      high-functioning autism spectrum disorder (ASD) patients (N = 165). To this end,
      the Autism Diagnostic Observation Schedule (ADOS), the Autism (AQ) and Empathy
      Quotient (EQ) self-rating questionnaires were applied back to back with the newly
      developed PAUSS. RESULTS: PAUSS differentiated between ASD, schizophrenia and a
      disease-control sample and substantially correlated with the Autism Diagnostic
      Observation Schedule. Patients with ADOS scores >=12 obtained highest, those with
      scores <7 lowest PAUSS values. AQ and EQ were not found to vary dependent on ADOS
      diagnosis. ROC curves for ADOS and PAUSS resulted in AuC values of 0.9 and 0.8,
      whereas AQ and EQ performed at chance level in the prediction of ASD.
      CONCLUSIONS: This work underscores the convergence of schizophrenia negative
      symptoms and autistic phenotypes. PAUSS evolved as a measure capturing the
      continuous nature of autistic behaviors. The definition of extreme-groups based
      on the dimensional PAUSS may permit future investigations of genetic
      constellations modulating autistic phenotypes.

PMID- 25968179
TI  - Lessons Learned From Adolescent Mothers: Advice on Recruitment.
AB  - PURPOSE: Adolescent mothers have high rates of depressive symptoms and inadequate
      rates of depression evaluation and treatment. The purpose of this qualitative
      study was to identify characteristics of effective recruitment ads for an
      Internet-based depression intervention for pregnant and parenting adolescents.
      METHODS: Using focus group methods, participants (N = 35) were recruited and
      enrolled at a teen parent program, part of the public school system. Focus group
      sessions were analyzed for participant preferences, rationale for choices, key
      words, and the frequency of words within the videotapes and audiotapes. RESULTS:
      Findings indicated that adolescent mothers preferred pictures in which everyone
      looked happy, narrative that clearly indicated cost and eligibility, and words
      that they would use in conversation. CLINICAL RELEVANCE: The study filled an
      important gap in the literature by soliciting from pregnant and parenting
      adolescents their preferences regarding visual appeal, content adequacy, and
      message clarity of advertisements that would motivate them to visit an Internet
      intervention for depression. Results could be extrapolated to education of
      pregnant and parenting adolescents in clinical settings.

PMID- 25968178
TI  - Degeneration of spinal motor neurons by chronic AMPA-induced excitotoxicity in
      vivo and protection by energy substrates.
AB  - INTRODUCTION: Several data suggest that excitotoxicity due to excessive
      glutamatergic neurotransmission may be an important factor in the mechanisms of
      motor neuron (MN) death occurring in amyotrophic lateral sclerosis (ALS). We have
      previously shown that the overactivation of the Ca(2+)-permeable alpha-amino-3
      hydroxy-5-methyl-4-isoxazole propionate (AMPA) glutamate receptor type, through
      the continuous infusion of AMPA in the lumbar spinal cord of adult rats during
      several days, results in progressive rear limb paralysis and bilateral MN
      degeneration. Because it has been shown that energy failure and oxidative stress
      are involved in MN degeneration, in both ALS and experimental models of spinal MN
      degeneration, including excitotoxicity, in this work we tested the protective
      effect of the energy substrates pyruvate and beta-hydroxybutyrate (betaHB) and
      the antioxidants glutathione ethyl ester (GEE) and ascorbate in this chronic AMPA
      induced neurodegeneration. RESULTS: AMPA infusion induced remarkable progressive
      motor deficits, assessed by two motor tasks, that by day seven reach bilateral
      rear limb paralysis. These effects correlate with the death of >80% of lumbar
      spinal MNs in the infused and the neighbor spinal cord segments, as well as with
      notable astrogliosis in the ventral horns, detected by glial fibrillary acidic
      protein immunohistochemistry. Co-infusion with pyruvate or betaHB notably
      prevented the motor deficits and paralysis, decreased MN loss to <25% and
      completely prevented the induction of astrogliosis. In contrast, the antioxidants
      tested were ineffective regarding all parameters analyzed. CONCLUSIONS: Chronic
      progressive excitotoxicity due to AMPA receptors overactivation results in MN
      death and astrogliosis, with consequent motor deficits and paralysis. Because of
      the notable protection against these effects exerted by pyruvate and betaHB,
      which are well established mitochondrial energy substrates, we conclude that
      deficits in mitochondrial energy metabolism are an important factor in the
      mechanisms of this slowly developed excitotoxic MN death, while the lack of
      protective effect of the antioxidants indicates that oxidative stress seems to be
      less significant factor. Because excitotoxicity may be involved in MN
      degeneration in ALS, these findings suggest possible preventive or therapeutic
      strategies for the disease.

PMID- 25968180
TI  - Impact of an ABCDE team triage process combined with public guidance on the
      division of work in an emergency department.
AB  - OBJECTIVE: To study the effects of applying an emergency department (ED) triage
      system, combined with extensive publicity in local media about the "right" use of
      emergency services, on the division of work between ED nurses and general
      practitioners (GPs). DESIGN: An observational and quasi-experimental study based
      on before-after comparisons. SETTING: Implementation of the ABCDE triage system
      in a Finnish combined ED where secondary care is adjacent, and in a traditional
      primary care ED where secondary care is located elsewhere. SUBJECTS: GPs and
      nurses from two different primary care EDs. MAIN OUTCOME MEASURES: Numbers of
      monthly visits to different professional groups before and after intervention in
      the studied primary care EDs and numbers of monthly visits to doctors in the
      local secondary care ED. RESULTS: The beginning of the triage process increased
      temporarily the number of independent consultations and patient record entries by
      ED nurses in both types of studied primary care EDs and reduced the number of
      patient visits to a doctor compared with previous years but had no effect on
      doctor visits in the adjacent secondary care ED. No further decrease in the
      number of nurse or GP visits was observed by inhibiting the entrance of non
      urgent patients. CONCLUSION: The ABCDE triage system combined with public
      guidance may reduce non-urgent patient visits to doctors in different kinds of
      primary care EDs without increasing visits in the secondary care ED. However, the
      additional work to implement the ABCDE system is mainly directed to nurses, which
      may pose a challenge for staffing.

PMID- 25968182
TI  - High-precision surface measurement with an automated multiangle low coherence
      interferometer.
AB  - We propose a novel measurement system based on a low coherence Michelson
      interferometer and six-axis hexapod platform to accurately measure structures
      with high aspect ratio using different tilt angles of the measured surface. In
      order to realize automatic measurement, the system is designed to automatically
      perform autofocusing, adjust the tilt angle of the test surface, make surface
      measurements, and merge the measurement data sets. Due to certain topography,
      e.g., structures with high aspect ratio, the interferometer cannot obtain enough
      reflected light to evaluate the height information in some areas of the test
      surface. For this reason, we developed a measurement system that uses
      measurements from different tilt angles of the test surface and stitching
      algorithms to realize a complete surface measurement data set. The performance of
      the proposed measurement system is evaluated experimentally and compared to the
      results of measurements using a perthometer. 

PMID- 25968181
TI  - Pseudomonas moraviensis subsp. stanleyae, a bacterial endophyte of
      hyperaccumulator Stanleya pinnata, is capable of efficient selenite reduction to
      elemental selenium under aerobic conditions.
AB  - AIMS: To identify bacteria with high selenium tolerance and reduction capacity
      for bioremediation of wastewater and nanoselenium particle production. METHODS
      AND RESULTS: A bacterial endophyte was isolated from the selenium
      hyperaccumulator Stanleya pinnata (Brassicaceae) growing on seleniferous soils in
      Colorado, USA. Based on fatty acid methyl ester analysis and multi-locus sequence
      analysis (MLSA) using 16S rRNA, gyrB, rpoB and rpoD genes, the isolate was
      identified as a subspecies of Pseudomonas moraviensis (97.3% nucleotide identity)
      and named P. moraviensis stanleyae. The isolate exhibited extreme tolerance to
      SeO3(2-) (up to 120 mmol l(-1)) and SeO4(2-) (>150 mmol l(-1)). Selenium oxyanion
      removal from growth medium was measured by microchip capillary electrophoresis
      (detection limit 95 nmol l(-1) for SeO3(2-) and 13 nmol l(-1) for SeO4(2-)).
      Within 48 h, P. moraviensis stanleyae aerobically reduced SeO3(2-) to red Se(0)
      from 10 mmol l(-1) to below the detection limit (removal rate 0.27 mmol h(-1) at
      30  degrees C); anaerobic SeO3(2-) removal was slower. No SeO4(2-) removal was
      observed. Pseudomonas moraviensis stanleyae stimulated the growth of crop species
      Brassica juncea by 70% with no significant effect on Se accumulation.
      CONCLUSIONS: Pseudomonas moraviensis stanleyae can tolerate extreme levels of
      selenate and selenite and can deplete high levels of selenite under aerobic and
      anaerobic conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: Pseudomonas
      moraviensis subsp. stanleyae may be useful for stimulating plant growth and for
      the treatment of Se-laden wastewater.

PMID- 25968183
TI  - Complete anisotropic time-dependent heat equation in KTP crystal under
      repetitively pulsed Gaussian beams: a numerical approach.
AB  - In this work, a thorough and detailed solution for the time-dependent heat
      equation for a cylindrical nonlinear potassium titanyl phosphate (KTP) crystal
      under a repetitively pulsed pumping source is developed. The convection and
      radiation boundary conditions, which are usually ignored in the literature, have
      been taken into account, and their importance on the temperature distribution has
      been discussed in detail. Moreover, the temperature dependence of thermal
      conductivity of KTP was considered in the calculations, and its impact is
      discussed. It is shown that the radiation term has a negligible effect and can be
      dropped safely, while the temperature dependence of thermal conductivity is more
      influential, such that ignorance of it brings some errors into the modeling. The
      time evolution of the temperature while the crystal is pumping with a train of
      successive Gaussian pulses until reaching equilibrium is shown. To accomplish
      numerical calculations, we developed a homemade code written with the finite
      difference time domain method in Intel Fortran (ifort) and ran it with the Linux
      operating system. 

PMID- 25968184
TI  - Tailoring the plasmonic whispering gallery modes of a metal-coated resonator for
      potential application as a refractometric sensor.
AB  - Plasmonic whispering gallery (WG) modes confined in metal-coated resonators are
      theoretically investigated by electromagnetic analyses. The resonance can be
      tuned from internal surface plasmonic WG modes to the hybrid state of the
      plasmonic mode by an introduced isolation layer. As the coated metal is reduced
      in size, the optical resonance is shifted out by the mode coupling of the
      internal and external surface plasmonic WG modes. Based on the optical leak of
      the plasmonic WG mode, the optical influences led by the surroundings with a
      variable refractive index are considered. Device performance criteria such as
      optical power leak, resonant wavelength shift, and threshold gain are studied.
      Full wave simulations are also employed and the results present good consistency
      with analytic solutions. The metal-coated resonator assisted by an active
      material is expected to provide promising performance as a refractometric sensor.

PMID- 25968185
TI  - Study of heat dissipation process from heat sink using lensless Fourier transform
      digital holographic interferometry.
AB  - This paper presents the results of experimental investigations about the heat
      dissipation process of plate fin heat sink using digital holographic
      interferometry. Visual inspection of reconstructed phase difference maps of the
      air field around the heat sink with and without electric power in the load
      resistor provides qualitative information about the variation of temperature and
      the heat dissipation process. Quantitative information about the temperature
      distribution is obtained from the relationship between the digitally
      reconstructed phase difference map of ambient air and heated air. Experimental
      results are presented for different current and voltage in the load resistor to
      investigate the heat dissipation process. The effect of fin spacing on the heat
      dissipation performance of the heat sink is also investigated in the case of
      natural heat convection. From experimental data, heat transfer parameters, such
      as local heat flux and convective heat transfer coefficients, are also
      calculated. 

PMID- 25968186
TI  - Realization of self-guided unidirectional waveguides by a chain of gyromagnetic
      rods.
AB  - To achieve a unidirectional transmission waveguide with miniature dimensions and
      flexible geometry, we propose a self-guided unidirectional waveguide composed of
      a chain of gyromagnetic rods. Two configurations of the waveguides were
      demonstrated. One is of a zigzag chain form, the other is a straight-line chain.
      These two types of waveguides have very wide one-way edge mode bandwidths. The
      simulated and experimental results illustrate their extraordinary wideband one
      way transmission characteristics. They can also be expected to function as
      flexible platforms for practical applications because of their thin transverse
      dimensions and robustness to bending. 

PMID- 25968187
TI  - Underwater optical communication performance for laser beam propagation through
      weak oceanic turbulence.
AB  - In clean ocean water, the performance of a underwater optical communication
      system is limited mainly by oceanic turbulence, which is defined as the
      fluctuations in the index of refraction resulting from temperature and salinity
      fluctuations. In this paper, using the refractive index spectrum of oceanic
      turbulence under weak turbulence conditions, we carry out, for a horizontally
      propagating plane wave and spherical wave, analysis of the aperture-averaged
      scintillation index, the associated probability of fade, mean signal-to-noise
      ratio, and mean bit error rate. Our theoretical results show that for various
      values of the rate of dissipation of mean squared temperature and the temperature
      salinity balance parameter, the large-aperture receiver leads to a remarkable
      decrease of scintillation and consequently a significant improvement on the
      system performance. Such an effect is more noticeable in the plane wave case than
      in the spherical wave case. 

PMID- 25968188
TI  - Polarization difference ghost imaging.
AB  - We propose the polarization difference ghost imaging method and experimentally
      demonstrate that polarization properties can provide additional information in
      conventional ghost imaging for object discrimination with contrast enhancement.
      In our experiment, two kinds of visually similar objects with different
      polarization properties can be separated for imaging. Meanwhile, an improved
      polarization difference algorithm is presented, fully utilizing the polarization
      discrepancy between objects and background, to further enhance the image
      contrast. Our work facilitates practical applications of ghost imaging. 

PMID- 25968189
TI  - Electromagnetically induced-transparency-like spectrum in an add/drop
      interferometer.
AB  - We propose a single-ring-resonator-based add/drop interferometer and
      theoretically investigate the transmission characteristics. Due to coherent
      interference of two resonant pathways, an electromagnetically induced
      transparency (EIT)-like spectrum is produced and the line shapes of the
      transmission spectra are tunable by controlling the coupling coefficients between
      the waveguide and ring resonator. We observe the EIT-like behavior in a fiber
      system which agrees well with the theoretical analysis. The proposed
      configuration has potential applications in tunable delay lines. 

PMID- 25968190
TI  - Performances of different subset shapes and control points in subset-based
      digital image correlation and their applications in boundary deformation
      measurement.
AB  - Digital image correlation (DIC) is an effective and popular tool for displacement
      and strain measurements. In the standard subset-based algorithms, the center
      point of a subset is considered by default as the control point for calculation,
      and it is difficult to obtain the deformation information at the boundary. Proper
      selection of the subset shape and the location of control points are vital to the
      displacement calculation at the boundary. In this paper, registration accuracies
      of several typical types of subset shapes and different locations of control
      points are investigated. The results illustrate that different choices of subset
      shapes can greatly affect the registration accuracy, while different choices for
      the locations of control points have little impact on it. Based on these results,
      the noncentral algorithm is developed for the whole-field deformation
      measurement. 

PMID- 25968191
TI  - Acoustic anisotropy of acoustooptic TI(3)AsS(4) crystals.
AB  - We present comprehensive experimental measurements and analysis of anisotropy of
      the acoustic wave velocities for TI(3)AsS(4) crystals, including the obliquity
      and nonorthogonality of the acoustic waves, and the deviations from purely
      longitudinal and transverse polarization types. We have found that the crystals
      under analysis are characterized by rather low transverse wave velocities v(23)
      and v(32), which are both equal to 630 m/s. It is shown that the efficiency of
      acoustooptic (AO) interactions in TI(3)AsS(4) can be notably increased when
      providing anisotropic interaction with the slowest transverse acoustic wave.
      Under the previously mentioned conditions, the AO figure-of-merit can be
      estimated to be extremely high, i.e., approximately 3*10(-12) s(3)/kg.

PMID- 25968192
TI  - Liquid-filled photonic-crystal-fiber-based multimodal interferometer for
      simultaneous measurement of temperature and force.
AB  - In this paper, a multimodal interferometer based on the liquid-filled photonic
      crystal fiber (PCF) has been proposed and experimentally demonstrated for
      simultaneous measurement of temperature and force. Experimental results show that
      different spectral minima have distinctive sensitivities to the temperature and
      force. The proposed interferometer shows the temperature sensitivities of -9.214
      nm/ degrees C, -24.757 nm/ degrees C, and -12.543/ degrees C and the force
      sensitivities of 0 nm/N, 4.978 nm/N, and 0 nm/N, respectively, for the three
      selected spectral minima. The sensing matrices are thus established and
      simultaneous measurement of temperature and force has been experimentally
      demonstrated. The proposed liquid-filled PCF-based multimodal interferometer
      would find potential applications in multiple-parameter sensing owing to its high
      sensitivity, compactness, ease of fabrication, and low cost.

PMID- 25968193
TI  - Gold-film coating assisted femtosecond laser fabrication of large-area, uniform
      periodic surface structures.
AB  - A simple, repeatable approach is proposed to fabricate large-area, uniform
      periodic surface structures by a femtosecond laser. 20 nm gold films are coated
      on semiconductor surfaces on which large-area, uniform structures are fabricated.
      In the case study of silicon, cross-links and broken structures of laser induced
      periodic surface structures (LIPSSs) are significantly reduced on Au-coated
      silicon. The good consistency between the scanning lines facilitates the
      formation of large-area, uniform LIPSSs. The diffusion of hot electrons in the Au
      films increases the interfacial carrier densities, which significantly enhances
      interfacial electron-phonon coupling. High and uniform electron density
      suppresses the influence of defects on the silicon and further makes the coupling
      field more uniform and thus reduces the impact of laser energy fluctuations,
      which homogenizes and stabilizes large-area LIPSSs. 

PMID- 25968194
TI  - Improved efficacy of warm-white light-emitting diode luminaires.
AB  - We present a novel approach to address one of the technical hurdles the current
      light-emitting diode (LED) lighting field faces: the packaged efficacy of warm
      white LEDs is 20%-30% lower than that of cool-white LEDs depending on the color
      rendering index. With a differentiated luminaire design in combination with a new
      class of nano materials, we have greatly improved the efficacy of warm white by
      15% at the luminaire system level, which translates to less energy being required
      to achieve the same light output, and thus offers a more energy-efficient
      solution. Reliability test of the luminaire shows no performance degradation
      within the tested period of more than 3000 h. A modeling has been developed to
      predict the optical performance of luminaires incorporating the nano materials,
      which agrees well with the experimental data and serves as a powerful tool for
      designing luminaires with targeted performance.

PMID- 25968195
TI  - Widely tunable third-harmonic generation in a tellurite microstructured optical
      fiber.
AB  - We designed and fabricated a tellurite (76.5TeO(2)-6Bi(2)O(3)-11.5Li(2)O-6ZnO,
      mol. %) microstructured optical fiber (TMOF) with four air holes for widely
      tunable third-harmonic generation (THG). The loss of the TMOF is ~0.2 dB/m at
      1550 nm. Widely tunable THG from ~567 to 902 nm is obtained when the TMOF is
      pumped by an optical parametric oscillator with the pump wavelength changing from
      ~1700 to 2700 nm. The mechanism of THG in this work is further investigated
      through the third-harmonic signal pattern, which is due to the high nonlinearity
      of the TMOF and the high pump power, not from the phase-matching process between
      the fundamental mode and the high-order TH mode.

PMID- 25968196
TI  - Refractometric sensitivity and thermal stabilization of fluorescent core
      microcapillary sensors: theory and experiment.
AB  - Fluorescent-core microcapillaries (FCMs) present a robust basis for the
      application of optical whispering gallery modes toward refractometric sensing. An
      important question concerns whether these devices can be rendered insensitive to
      local temperature fluctuations, which may otherwise limit their refractometric
      detection limits, mainly as a result of thermorefractive effects. Here, we first
      use a standard cylindrical cavity formalism to develop the refractometric and
      thermally limited detection limits for the FCM structure. We then measure the
      thermal response of a real device with different analytes in the channel and
      compare the result to the theory. Good stability against temperature fluctuations
      was obtained for an ethanol solvent, with a near-zero observed thermal shift for
      the transverse magnetic modes. Similarly good results could in principle be
      obtained for any other solvent (e.g., water), if the thickness of the fluorescent
      layer can be sufficiently well controlled. 

PMID- 25968197
TI  - Deflection tomographic reconstructions of a three-dimensional flame structure and
      temperature distribution of premixed combustion.
AB  - The distribution of premixed combustion parameters and the flame structure were
      investigated in this work using deflection tomography technology. A deflection
      tomographic apparatus was presented to obtain chronological arrays of
      multidirectional deflectograms. The hybrid regularization method was employed to
      reconstruct the temperature distributions in each cross section. The numerical
      simulation approach produced reliable reconstructions by computing
      underdetermined and overdetermined equations for asymmetrical distribution.
      Visualization technology with the matching cube and ray casting algorithms was
      applied in three-dimensional visualization. In the work, temperature
      distributions in five cross sections of the premixed combustion were
      reconstructed using six view-angle projection data inversions. Three-dimensional
      flame structures and temperature distributions in the flame interior were
      visualized using the visualization tool kit. 

PMID- 25968198
TI  - Fully automated low-cost setup for fringe projection profilometry.
AB  - In this paper an alternative low-cost, easy-to-use, and fully automated
      profilometry setup is proposed. The setup is based on a phase-shifting fringe
      projection technique with four projected fringe parameters. It uses the well
      known triangulation arrangement and low-cost electronic and image acquisition
      components such as a data acquisition board, a motor controller board, a printer
      rail, a CMOS webcam, and an LCD projector. The position of the camera, the
      generation of the fringe pattern, the acquisition of the images, and the
      calculation of the wrapped and unwrapped phase are all performed in LabVIEW. The
      setup is portable and can be perfectly adapted to be used in other profilometry
      techniques such as electronic speckle pattern interferometry and laser scanning
      profilometry. 

PMID- 25968200
TI  - Influence of spatial incident angles on polarizer with a slit in grooved metal
      slabs for terahertz communication.
AB  - We report the influence of two spatial incident angles on a terahertz polarizer,
      which is based on an aluminum slab with a center slit flanked by symmetrically
      distributed parallel grooves on both sides. Experimental results show that the
      polarizer shows narrow bandpass filtering effect with a very small divergence
      angle at normal incidence, which is very suitable for terahertz communication,
      and the extinction ratio (ER) can be achieved above 20 dB in the frequency band
      between 0.3 and 0.36 THz due to the excitation of spoof surface plasmon. As the
      structure rotates around the slit direction (beta), the transmission peak will
      split into two and degrade quickly and the ER decreased down to 20 dB for beta=10
      degrees  at peak position. Rotating along grating period direction (gamma) shows
      better tuning performance. The tuning frequency window can reach from 0.3 to 0.36
      THz to promise an ER above 20 dB as gamma is smaller than 25 degrees .

PMID- 25968199
TI  - Improvements of axial resolution in confocal microscopy with fan-shaped
      apertures.
AB  - Based on diffraction theory, this paper theoretically demonstrates improvements
      in axial resolution in confocal microscopy with fan-shaped apertures. It provides
      the optimal geometric parameters of the fan-shaped pupils to give the maximum
      axial resolution for a given pinhole size. To fully understand the overall
      performance, the signal-to-background ratio and the signal level with regard to
      the geometric parameters are discussed. 

PMID- 25968201
TI  - Dynamic properties of a metal photo-thermal micro-actuator.
AB  - This work presents the design, modeling, simulation, and characterization of a
      metal bent-beam photo-thermal micro-actuator. The mechanism of actuation is based
      on the thermal expansion of the micro-actuator which is irradiated by a laser,
      achieving noncontact control of the power supply. Models for micro-actuators were
      established and finite-element simulations were carried out to investigate the
      effects of various parameters on actuation properties. It is found that the
      thermal expansion coefficient, thermal conductivity, and the geometry size
      largely affected actuation behavior whereas heat capacity, density, and Young's
      modulus did not. Experiments demonstrated the dynamic properties of a Ni micro
      actuator fabricated via LIGA technology with 1100/30/100 MUm (long/wide/thick)
      arms. The tip displacement of the micro-actuator could achieve up to 42 MUm
      driven by a laser beam (1064 nm wavelength, 1.2 W power, and a driving frequency
      of 1 HZ). It is found that the tip displacement decreases with increasing laser
      driving frequency. For 8 Hz driving frequency, 17 MUm (peak-valley value) can be
      still reached, which is large enough for the application as micro-electro
      mechanical systems. Metal photo-thermal micro actuators have advantages such as
      large displacement, simple structure, and large temperature tolerance, and
      therefore they will be promising in the fields of micro/nanotechnology.

PMID- 25968202
TI  - Experimental measurements of the spectral absorption coefficient of pure fused
      silica optical fibers.
AB  - Knowledge of the spectral absorption coefficient of fused silica optical fibers
      is important in modeling heat transfer in the processes and applications in which
      these fibers are used. An experimental method used to measure the spectral
      absorption coefficient of optical fibers is presented. Radiative energy from a
      blackbody radiator set at different temperatures is directed through the optical
      fibers and into an FTIR spectrometer. Spectral instrument response functions are
      calculated for different fiber lengths. The ratios of the slopes of the
      instrument response functions for the different lengths of fibers are used to
      solve for the spectral absorption coefficient of the fibers. The spectral
      absorption coefficient of low OH pure fused silica optical fibers is measured
      between the wavelengths 1.5 and 2.5 MUm.

PMID- 25968203
TI  - Predictive capability of average Stokes polarimetry for simulation of phase
      multilevel elements onto LCoS devices.
AB  - Parallel-aligned (PA) liquid-crystal on silicon (LCoS) microdisplays are
      especially appealing in a wide range of spatial light modulation applications
      since they enable phase-only operation. Recently we proposed a novel polarimetric
      method, based on Stokes polarimetry, enabling the characterization of their
      linear retardance and the magnitude of their associated phase fluctuations or
      flicker, exhibited by many LCoS devices. In this work we apply the calibrated
      values obtained with this technique to show their capability to predict the
      performance of spatially varying phase multilevel elements displayed onto the PA
      LCoS device. Specifically we address a series of multilevel phase blazed
      gratings. We analyze both their average diffraction efficiency ("static"
      analysis) and its associated time fluctuation ("dynamic" analysis). Two different
      electrical configuration files with different degrees of flicker are applied in
      order to evaluate the actual influence of flicker on the expected performance of
      the diffractive optical elements addressed. We obtain a good agreement between
      simulation and experiment, thus demonstrating the predictive capability of the
      calibration provided by the average Stokes polarimetric technique. Additionally,
      it is obtained that for electrical configurations with less than 30 degrees 
      amplitude for the flicker retardance, they may not influence the performance of
      the blazed gratings. In general, we demonstrate that the influence of flicker
      greatly diminishes when the number of quantization levels in the optical element
      increases. 

PMID- 25968204
TI  - Evaluation of an airborne triple-pulsed 2 MUm IPDA lidar for simultaneous and
      independent atmospheric water vapor and carbon dioxide measurements.
AB  - Water vapor and carbon dioxide are the most dominant greenhouse gases directly
      contributing to the Earth's radiation budget and global warming. A performance
      evaluation of an airborne triple-pulsed integrated path differential absorption
      (IPDA) lidar system for simultaneous and independent monitoring of atmospheric
      water vapor and carbon dioxide column amounts is presented. This system leverages
      a state-of-the-art Ho:Tm:YLF triple-pulse laser transmitter operating at 2.05 MUm
      wavelength. The transmitter provides wavelength tuning and locking capabilities
      for each pulse. The IPDA lidar system leverages a low risk and technologically
      mature receiver system based on InGaAs pin detectors. Measurement methodology and
      wavelength setting are discussed. The IPDA lidar return signals and error budget
      are analyzed for airborne operation on-board the NASA B-200. Results indicate
      that the IPDA lidar system is capable of measuring water vapor and carbon dioxide
      differential optical depth with 0.5% and 0.2% accuracy, respectively, from an
      altitude of 8 km to the surface and with 10 s averaging. Provided availability of
      meteorological data, in terms of temperature, pressure, and relative humidity
      vertical profiles, the differential optical depth conversion into weighted
      average column dry-air volume-mixing ratio is also presented.

PMID- 25968205
TI  - Optimal design of one-dimensional photonic crystal filters using minimax
      optimization approach.
AB  - In this paper, we introduce a simulation-driven optimization approach for
      achieving the optimal design of electromagnetic wave (EMW) filters consisting of
      one-dimensional (1D) multilayer photonic crystal (PC) structures. The PC layers'
      thicknesses and/or material types are considered as designable parameters. The
      optimal design problem is formulated as a minimax optimization problem that is
      entirely solved by making use of readily available software tools. The proposed
      approach allows for the consideration of problems of higher dimension than
      usually treated before. In addition, it can proceed starting from bad initial
      design points. The validity, flexibility, and efficiency of the proposed approach
      is demonstrated by applying it to obtain the optimal design of two practical
      examples. The first is (SiC/Ag/SiO(2))(N) wide bandpass optical filter operating
      in the visible range. Contrarily, the second example is (Ag/SiO(2))(N) EMW low
      pass spectral filter, working in the infrared range, which is used for enhancing
      the efficiency of thermophotovoltaic systems. The approach shows a good ability
      to converge to the optimal solution, for different design specifications,
      regardless of the starting design point. This ensures that the approach is robust
      and general enough to be applied for obtaining the optimal design of all 1D
      photonic crystals promising applications.

PMID- 25968206
TI  - Design of a high-quality optical conjugate structure in optical tweezers.
AB  - We propose an approach to realize a high-quality optical conjugate of a piezo
      driven mirror (PM) in optical tweezers. Misalignments between the optical beam
      and the steering center of the PM are analyzed mathematically. The decentrations
      in different directions cause different changes, either a position change of the
      conjugate plane or a spot variation of the beam during PM steering. On the other
      hand, these misalignment-introduced problems provide the information to check the
      assembling errors. Thus a wanted conjugate plane of the PM can be effectively and
      precisely achieved according to the detection signals. This approach is also
      available to deal with multifactor coupling error. At the end, the procedure for
      error analysis is given by testing homebuilt optical tweezers. 

PMID- 25968207
TI  - Resolution characteristics of graded doping and graded composition transmission
      mode AlGaAs/GaAs photocathodes.
AB  - The resolution model of a graded doping and graded composition transmission-mode
      AlGaAs/GaAs photocathode is solved numerically from the two-dimensional
      continuity equations. According to the model, we calculate the theoretical
      modulation transfer function (MTF) of different graded doping and graded
      composition structures. The simulation results show that both graded composition
      and graded doping structures can increase the resolution of the photocathode. The
      exponentially doping and linear composition photocathode has the maximum
      resolution among the possible graded doping and graded composition photocathodes.
      The resolution improvement is attributed to the built-in electric field induced
      by a graded composition or graded doping structure. The simulation results also
      show that the MTFs of AlGaAs/GaAs cathodes increase as the AlGaAs layer thickness
      decreases, or the incident light wavelength increases. 

PMID- 25968208
TI  - Ferrofluid-based optofluidic switch using femtosecond laser-micromachined
      waveguides.
AB  - We present a portable optofluidic switch using a ferrofluid plug in a
      commercially produced microfluidic chip with waveguides added via femtosecond
      laser micromachining (FLM). FLM enabled the one-step fabrication of highly
      reproducible, perfectly aligned integrated waveguides orthogonally crossing an
      existing microfluidic channel. In the "ON" state for each output, the ferrofluid
      plug is outside the intersection and input light arrives at the output with
      relatively small loss. In the "OFF" state, the plug is inside the intersection
      and the input light is absorbed. The same plug is used to turn ON and OFF several
      parallel waveguides with contrast ratios of 22 dB or better. In addition, the
      plug is driven periodically using an electromagnet combined with a permanent
      magnet for frequency-dependent characterization. Photodiode data show high
      contrast up to 50 Hz and linear frequency response up to 1 KHz.

PMID- 25968209
TI  - Numerical modeling considerations for an applied nonlinear Schrodinger equation.
AB  - A model for nonlinear optical propagation is cast into a split-step numerical
      framework via a variable stencil-size Crank-Nicolson finite-difference method for
      the linear step and a choice of two different nonlinear integration schemes for
      the nonlinear step. The model includes Kerr, Raman scattering, and ionization
      effects (as well as linear and nonlinear shock, diffraction, and dispersion). We
      demonstrate the practical importance of numerical effects when interpreting
      computational studies of high-intensity optical pulse propagation in physical
      materials. Examples demonstrate the significant error that can arise in discrete,
      limited precision implementations as one attempts to improve practical operator
      accuracy through increased operator support size and sampling frequency. We also
      demonstrate the effect of the method used to obtain the finite-difference
      operator coefficients defining the equations ultimately used in the discrete
      model. Smooth, plausible, but incorrect solutions may result from these numerical
      effects. This implies the necessity of a complete, precise description of all
      numerical methods when reporting results of computational physics investigations
      in order to ensure proper interpretation and reproducibility. 

PMID- 25968210
TI  - Autostigmatic microscope and how it works.
AB  - The autostigmatic microscope (ASM) is ubiquitous in the applied optics community
      and so familiar to those who regularly use it that it is barely mentioned in the
      literature. In some well-known applied optics books, the ASM's use is implied
      without ever being explicitly acknowledged because the authors assume no
      explanation is needed. However, each new generation of optical engineers need to
      be made aware of the workings and usefulness of the ASM, a tool every bit as
      useful as an autocollimator or alignment telescope. This note is an attempt to do
      just that. 

PMID- 25968211
TI  - Optical tolerancing and principal component analysis.
AB  - This work explores the use of linear principal component analysis (PCA) during an
      optical design's tolerancing analysis. Chapman et al. [Proc. SPIE3331, 102
      (1998)PSISDG0277-786X] have shown the usefulness of the singular value
      decomposition in realizing an alignment algorithm for a system. This paper
      explores some insights that can be gained from performing PCA on the Monte Carlo
      data set obtained during the tolerancing step and comparing it with the singular
      components of the Jacobian (sensitivity matrix) of the system.

PMID- 25968212
TI  - Application of up-sampling and resolution scaling to Fresnel reconstruction of
      digital holograms.
AB  - Fresnel transform implementation methods using numerical preprocessing techniques
      are investigated in this paper. First, it is shown that up-sampling dramatically
      reduces the minimum reconstruction distance requirements and allows maximal
      signal recovery by eliminating aliasing artifacts which typically occur at
      distances much less than the Rayleigh range of the object. Second, zero-padding
      is employed to arbitrarily scale numerical resolution for the purpose of
      resolution matching multiple holograms, where each hologram is recorded using
      dissimilar geometric or illumination parameters. Such preprocessing yields
      numerical resolution scaling at any distance. Both techniques are extensively
      illustrated using experimental results. 

PMID- 25968213
TI  - Coherent free space optics communications over the maritime atmosphere with use
      of adaptive optics for beam wavefront correction.
AB  - We evaluate the performance of the coherent free space optics (FSO) employing
      quadrature array phase-shift keying (QPSK) modulation over the maritime
      atmosphere with atmospheric turbulence compensated by use of adaptive optics
      (AO). We have established a comprehensive FSO channel model for maritime
      conditions and also made a comprehensive comparison of performance between the
      maritime and terrestrial atmospheric links. The FSO links are modeled based on
      the intensity attenuation resulting from scattering and absorption effects, the
      log-amplitude fluctuations, and the phase distortions induced by turbulence. The
      obtained results show that the FSO system performance measured by the bit-error
      rate (BER) can be significantly improved when the optimization of the AO system
      is achieved. Also, we find that the higher BER is observed in the maritime FSO
      channel with atmospheric turbulence, as compared to the terrestrial FSO systems
      if they experience the same turbulence strength. 

PMID- 25968214
TI  - Investigations on laser damage growth in fused silica with simultaneous
      wavelength irradiation.
AB  - The laser-induced damage growth phenomenon is experimentally studied for damage
      sites on the exit surface of fused silica. The sites are irradiated by nanosecond
      laser pulses at 1064 and 355 nm separately and also simultaneously. The results
      in the single wavelength configurations are expressed in terms of the probability
      of growth and growth coefficient. For growing sites, a fluence correction
      expression is proposed in order to take into account the millimetric Gaussian
      profile of the beams. The use of this expression is necessary to obtain results
      that are consistent with the ones obtained in the existing literature with large
      homogeneous beams. In the multiple wavelengths configuration, the results are
      expressed as a function of the laser fluences at each wavelength and are found to
      be closely related to the parameters determined in the single wavelength
      experiments. A coupling between the two wavelengths is quantified, and could
      originate from the formation and the expansion of a plasma produced both in the
      center and at the periphery of the damage sites.

PMID- 25968215
TI  - Packet error rate analysis of digital pulse interval modulation in intersatellite
      optical communication systems with diversified wavefront deformation.
AB  - Diversified wavefront deformation is an inevitable phenomenon in intersatellite
      optical communication systems, which will decrease system performance. In this
      paper, we investigate the description of wavefront deformation and its influence
      on the packet error rate (PER) of digital pulse interval modulation (DPIM). With
      the wavelet method, the diversified wavefront deformation can be described by
      wavelet parameters: coefficient, dilation, and shift factors, where the
      coefficient factor represents the depth, dilation factor represents the area, and
      shift factor is for location. Based on this, the relationship between PER and
      wavelet parameters is analyzed from a theoretical viewpoint. Numerical results
      illustrate the validity of theoretical analysis: PER increases with the depth and
      area and decreases if location gets farther from the center of the optical
      antenna. In addition to describing diversified deformation, the advantage of the
      wavelet method over Zernike polynomials in computational complexity is shown via
      numerical example. This work provides a feasible method for the description along
      with influence analysis of diversified wavefront deformation from a practical
      viewpoint and will be helpful for designing optical systems. 

PMID- 25968216
TI  - Research of polishing process to control the iron contamination on the
      magnetorheological finished KDP crystal surface.
AB  - A new nonaqueous and abrasive-free magnetorheological finishing (MRF) method is
      adopted for processing a KDP crystal. MRF polishing is easy to result in the
      embedding of carbonyl iron (CI) powders; meanwhile, Fe contamination on the KDP
      crystal surface will affect the laser induced damage threshold seriously. This
      paper puts forward an appropriate MRF polishing process to avoid the embedding.
      Polishing results show that the embedding of CI powders can be avoided by
      controlling the polishing parameters. Furthermore, on the KDP crystal surface,
      magnetorheological fluids residua inevitably exist after polishing and in which
      the Fe contamination cannot be removed completely by initial ultrasonic cleaning.
      To solve this problem, a kind of ion beam figuring (IBF) polishing is introduced
      to remove the impurity layer. Then the content of Fe element contamination and
      the depth of impurity elements are measured by time of flight secondary ion mass
      spectrometry. The measurement results show that there are no CI powders embedding
      in the MRF polished surface and no Fe contamination after the IBF polishing
      process, respectively. That verifies the feasibility of MRF polishing-IBF
      polishing (cleaning) for processing a KDP crystal. 

PMID- 25968217
TI  - Microgenetic optimization algorithm for optimal wavefront shaping.
AB  - One of the main limitations of utilizing optimal wavefront shaping in imaging and
      authentication applications is the slow speed of the optimization algorithms
      currently being used. To address this problem we develop a microgenetic
      optimization algorithm (MUGA) for optimal wavefront shaping. We test the
      abilities of the MUGA and make comparisons to previous algorithms (iterative and
      simple-genetic) by using each algorithm to optimize transmission through an
      opaque medium. From our experiments we find that the MUGA is faster than both the
      iterative and simple-genetic algorithms and that both genetic algorithms are more
      resistant to noise and sample decoherence than the iterative algorithm. 

PMID- 25968218
TI  - Reflection and transmission calculations in a multilayer structure with coherent,
      incoherent, and partially coherent interference, using the transmission line
      method.
AB  - A generalized transmission line method (TLM) that provides reflection and
      transmission calculations for a multilayer dielectric structure with coherent,
      partial coherent, and incoherent layers is presented. The method is deployed on
      two different application fields. The first application of the method concerns
      the thickness measurement of the individual layers of an organic light-emitting
      diode. By using a fitting approach between experimental spectral reflectance
      measurements and the corresponding TLM calculations, it is shown that the
      thickness of the films can be estimated. The second application of the TLM
      concerns the calculation of the external quantum efficiency of an organic
      photovoltaic with partially coherent rough interfaces between the layers.
      Numerical results regarding the short circuit photocurrent for different layer
      thicknesses and rough interfaces are provided and the performance impact of the
      rough interface is discussed in detail. 

PMID- 25968219
TI  - Aerosol optical properties and precipitable water vapor column in the atmosphere
      of Norway.
AB  - Between February 2012 and April 2014, we measured and analyzed direct solar
      radiances at a ground-based station in Bergen, Norway. We discovered that the
      spectral aerosol optical thickness (AOT) and precipitable water vapor column
      (PWVC) retrieved from these measurements have a seasonal variation with highest
      values in summer and lowest values in winter. The highest value of the monthly
      median AOT at 440 nm of about 0.16 was measured in July and the lowest of about
      0.04 was measured in December. The highest value of the monthly median PWVC of
      about 2.0 cm was measured in July and the lowest of about 0.4 cm was measured in
      December. We derived Angstrom exponents that were used to deduce aerosol particle
      size distributions. We found that coarse-mode aerosol particles dominated most of
      the time during the measurement period, but fine-mode aerosol particles dominated
      during the winter seasons. The derived Angstrom exponent values suggested that
      aerosols containing sea salt could have been dominating at this station during
      the measurement period.

PMID- 25968220
TI  - Planar THz electromagnetic graphene pass-band filter with low polarization and
      angle of incidence dependencies.
AB  - We propose and analyze a graphene electromagnetic filter for the terahertz (THz)
      region. The filter represents a planar square array of graphene elements. A unit
      cell of the array is formed by two coaxial graphene rings placed on the opposite
      sides of a thin dielectric substrate. The two electromagnetically coupled rings
      resonate with dipole plasmonic modes. The rings have slightly different
      dimensions and consequently different yet close individual resonant frequencies.
      At a frequency lying between these two resonances, the currents in the two
      interacting rings have opposite directions. This leads to a suppression of the
      reflected from the array waves and consequently to a high transmission through
      the array. For the chemical potential of the graphene MU<sub>c</sub>=0.6 eV, the
      calculated quality factor of this resonant mode is Q=5 at the frequency f=0.8 
      THz. At this frequency, the reflection coefficient of the array equals -36 dB and
      the transmission peak which is defined by the graphene losses is -1.8 dB. We show
      that the frequency position of the transmission peak can be varied in a wide
      range by the graphene chemical potential.

PMID- 25968221
TI  - Quantitative measurement and control of optical Moire pattern in an
      autostereoscopic liquid crystal display system.
AB  - A quantitative description of an optical moire pattern produced in an
      autostereoscopic liquid crystal display system is proposed using a contrast
      sensitivity function. The numerical simulation, carried out in the spatial
      frequency domain, is applied to a directional backlit, spatially and temporally
      hybrid controlled display system. The moire pattern produced from the
      superimposed binary optical components is examined systematically, and the
      results show that the visibility of the moire pattern can be manipulated with
      proper grating settings. Good agreement between experiment and simulation
      demonstrates that the proposed theory can be applied as a design guideline to
      remove the moire patterns occurring in an autostereoscopic display system. 

PMID- 25968222
TI  - Polarization and propagation characteristics of switchable first-order
      azimuthally asymmetric beam generated in dual-mode fiber.
AB  - We report here the controlled generation of a linearly polarized first-order
      azimuthally asymmetric beam (F-AAB) in a dual-mode fiber (DMF) by appropriate
      superposition of selectively excited zeroth-order vector modes that are doughnut
      shaped azimuthally symmetric beams (D-ASBs). We first demonstrate continually
      switching polarization mode structures having an identical two-lobe intensity
      profile (i.e., intra-F-AAB conversion). Then, under a distinct launching state,
      we generate mode structures progressively toggling between the doughnut-shaped
      profile and two-lobe pattern having dissimilar polarization orientations (i.e., F
      AAB to D-ASB conversion). Interestingly, a decentralized elliptical Gaussian beam
      possessing homogenous spatial polarization is obtained by enhancing the
      contribution of the fundamental mode (HE<sub>11</sub>/LP<sub>01</sub>) in
      selectively excited F-AAB. A smoothly varying azimuth of the input beam in this
      situation resulted in redistribution of transverse energy procuring a unique and
      exciting unconventional two-grain T-polarized beam having mutually orthogonal
      state of polarization (SOP). All of the above three were achieved under a given
      set of launching conditions (tilt/offset) of a Gaussian mode (TEM<sub>00</sub>)
      devised with changing SOP of the input beam. A strong modulation in the output
      beam characteristics was also observed with the variation in propagation distance
      (for a fixed input SOP) owing to the large difference in propagation constants of
      the participating modes (LP<sub>01</sub> and one of the F-AABs). Finally, this
      particular study led to a design for a low-cost highly sensitive strain measuring
      device based on tracking the centroid movement of the output intensity pattern.
      Each of our experimentally observed intensity/polarization distributions is
      theoretically mapped on a one-to-one basis considering a linear superposition of
      appropriately excited LP basis modes of the waveguide toward a complete
      understanding of the polarization and mode propagation in the dual-mode
      structure. 

PMID- 25968223
TI  - Slow light with large group index-bandwidth product in ellipse-hole photonic
      crystal waveguides.
AB  - In this study, we propose a new type of slow light photonic crystal waveguide
      structure to achieve wideband slow light with low dispersion. The waveguide is
      based on a triangular lattice ellipse-hole photonic crystal imposed simply by a
      selective altering of the locations of the holes adjacent to the line defect.
      Under a constant group index criterion of +/-10% variation, when group indices
      are nearly constants of 54, 69, and 80, their corresponding bandwidths of the
      flat band reach 12.7, 10.0, and 8.6 nm around 1550 nm, respectively. A nearly
      constant large group index-bandwidth product of 0.44 is achieved for all cases.
      Low dispersion slow light propagation is confirmed by studying the relative
      temporal pulse-width spreading with the two-dimensional finite-difference time
      domain method.

PMID- 25968224
TI  - Grating surface plasmon resonance sensor: angular sensitivity, metal oxidization
      effect of Al-based device in optimal structure.
AB  - We present the wavelength (lambda)-independent ultimate and maximum angular
      sensitivity of a grating surface plasmon resonance sensor, as long as the grating
      of metal has much higher permittivity than analyte (na2). For 1.32<=n(a)<=1.36,
      the maximum angular sensitivity reaches 493.7 (535.9) degrees /RIU by the single
      (double)-dip method. The real Al-based sensor in an optimal structure for a high
      figure of merit exhibits higher sensitivity but narrower reflection dip when
      working at a longer wavelength, and the real sensitivity increases from 292.5
      (344.5) to 338.0 (396.3) degrees /RIU at respective lambda=0.85 and 1.55 MUm
      before the metal oxidation. After the oxidization, the sensitivity is degraded by
      <=3.2% (2.8%), and the detection error of deltan(a)<=1.3e-3 (1.1e-3) is
      introduced to the sensor working at near-infrared wavelengths of interest.

PMID- 25968225
TI  - Engineering and laboratory notes: introduction.
AB  - Engineering & Laboratory Notes are introduced as a new monthly feature of Applied
      Optics. 

PMID- 25968226
TI  - Sex Differences in Longevity and in Responses to Anti-Aging Interventions: A Mini
      Review.
AB  - A robust, often underappreciated, feature of human biology is that women live
      longer than men not just in technologically advanced, low-mortality countries
      such as those in Europe or North America, but across low- and high-mortality
      countries of the modern world as well as through history. Women's survival
      advantage is not due to protection from one or a few diseases. Women die at lower
      rates than men from virtually all the top causes of death with the notable
      exception of Alzheimer's disease, to which women are particularly prone. Yet,
      despite this robust survival advantage, women across countries of the world
      suffer worse health throughout life. The biological mechanisms underlying either
      longer female survival or poorer female health remain elusive and understudied.
      Mechanisms of mammalian biology, particularly with respect to aging and disease,
      are most easily studied in laboratory mice. Although there are no consistent
      differences in longevity between mouse sexes even within single genotypes, there
      are often substantial differences in individual studies, sometimes favoring
      females, other times males. Investigating the environmental causes of this
      puzzling variation in longevity differences could prove illuminating. Sex
      differences in response to life-extending genetic or pharmacological
      interventions appear surprisingly often in mice. Longevity enhancement due to
      reduced signaling through IGF-1 or mTOR signaling typically favors females,
      whereas enhancement via a range of pharmacological treatments favors males. These
      patterns could be due to interactions of the interventions with sex steroids,
      with adiponectin or leptin levels, or with the sex differences in immune function
      or the regional distribution of body fat. Clearly, generalizations from one sex
      cannot be extended to the other, and inclusion of both sexes in biomedical
      studies of human or other animals is worth the effort and expense. 

PMID- 25968227
TI  - Effects of Variable Resistance Training on Maximal Strength: A Meta-Analysis.
AB  - Variable resistance training (VRT) methods improve the rate of force development,
      coordination between antagonist and synergist muscles, the recruitment of motor
      units, and reduce the drop in force produced in the sticking region. However, the
      beneficial effects of long-term VRT on maximal strength both in athletes and
      untrained individuals have been much disputed. The purpose of this study was to
      compare in a meta-analysis the effects of a long-term (>=7 weeks) VRT program
      using chains or elastic bands and a similar constant resistance program in both
      trained adults practicing different sports and untrained individuals.
      Intervention effect sizes were compared among investigations meeting our
      selection and inclusion criteria using a random-effects model. The published
      studies considered were those addressing VRT effects on the 1 repetition maximum.
      Seven studies involving 235 subjects fulfilled the selection and inclusion
      criteria. Variable resistance training led to a significantly greater mean
      strength gain (weighted mean difference: 5.03 kg; 95% confidence interval: 2.26
      7.80 kg; Z = 3.55; p < 0.001) than the gain recorded in response to conventional
      weight training. Long-term VRT training using chains or elastic bands attached to
      the barbell emerged as an effective evidence-based method of improving maximal
      strength both in athletes with different sports backgrounds and untrained
      subjects.

PMID- 25968228
TI  - Does the Dumbbell-Carrying Position Change the Muscle Activity in Split Squats
      and Walking Lunges?
AB  - The forward walking lunge (WL) and split squat (SSq) are similar exercises that
      have differences in the eccentric phase, and both can be performed in the
      ipsilateral or contralateral carrying conditions. This study aimed to determine
      the effects of dumbbell-carrying position on the kinematics and electromyographic
      (EMG) amplitudes of the gluteus medius (Gmed), vastus medialis (VM), vastus
      lateralis (VL), and biceps femoris during WLs and SSqs. The resistance-trained
      (RT) and the non-resistance-trained (NT) groups (both n = 14) performed
      ipsilateral WLs, contralateral WLs, ipsilateral SSqs, and contralateral SSqs in a
      randomized order in a simulated training session. The EMG amplitude, expressed as
      a percentage of the maximal voluntary isometric contraction (%MVIC), and the
      kinematics, expressed as the range of motion (ROM) of the hip and knee, were
      measured during 5 repetition maximum for both legs. The repeated measure analyses
      of variance showed significant differences between the RT and NT groups. The NT
      group showed a smaller knee flexion ROM (p < 0.001, eta = 0.36) during both types
      of WLs, whereas the RT group showed a higher eccentric Gmed amplitude (p < 0.001,
      eta = 0.46) during all exercises and a higher eccentric VL amplitude (p < 0.001,
      eta = 0.63) during contralateral WLs. Further differences were found between
      contralateral and ipsilateral WLs in both the RT (p < 0.001, eta = 0.69) and NT
      groups (p < 0.001, eta = 0.80), and contralateral WLs resulted in higher
      eccentric Gmed amplitudes. Contralateral WLs highly activated the Gmed (90%
      MVIC); therefore, this exercise can increase the Gmed maximal strength. The
      ipsilateral loading condition did not increase the Gmed or VM activity in the RT
      or NT group.

PMID- 25968229
TI  - Postactivation Potentation Effects From Accommodating Resistance Combined With
      Heavy Back Squats on Short Sprint Performance.
AB  - Applying accommodating resistance combined with isoinertial resistance has been
      demonstrated to be effective in improving neuromuscular attributes important for
      sport performance. The main purpose of this study was to determine whether short
      sprints can be acutely enhanced after several sets of back squats with or without
      accommodating resistance. Twenty recreationally resistance-trained males (age:
      23.3 +/- 4.4 years; height: 178.9 +/- 6.5 cm; weight: 88.3 +/- 10.8 kg) performed
      pre-post testing on 9.1-m sprint time. Three different interventions were
      implemented in randomized order between pre-post 9.1-m sprints. On 3 separate
      days, subjects either sat for 5 minutes (CTRL), performed 5 sets of 3 repetitions
      at 85% of their 1 repetition maximum (1RM) with isoinertial load (STND), or
      performed 5 sets of 3 repetitions at 85% of their 1RM, with 30% of the total
      resistance coming from elastic band tension (BAND) between pre-post 9.1-m sprint
      testing. Posttesting for 9.1-m sprint time occurred immediately after the last
      set of squats (Post-Immediate) and on every minute for 4 minutes after the last
      set of squats (Post-1min, Post-2min, Post-3min, and Post-4min). Repeated-measures
      analysis of variance statistical analyses revealed no significant changes in
      sprint time across posttesting times during the CTRL and STND condition. During
      the BAND condition, sprint time significantly decreased from Post-Immediate to
      Post-4min (p = 0.002). The uniqueness of accommodating resistance could create an
      optimal postactivation potentiation effect to increase neuromuscular performance.
      Coaches and athletes can implement heavy accommodating resistance exercises to
      their warm-up when improving acute sprint time is desired.

PMID- 25968231
TI  - Multiple attack on bacteria by the new antibiotic teixobactin.

PMID- 25968230
TI  - DisCons: a novel tool to quantify and classify evolutionary conservation of
      intrinsic protein disorder.
AB  - BACKGROUND: Analyzing the amino acid sequence of an intrinsically disordered
      protein (IDP) in an evolutionary context can yield novel insights on the
      functional role of disordered regions and sequence element(s). However, in the
      case of many IDPs, the lack of evolutionary conservation of the primary sequence
      can hamper the study of functionality, because the conservation of their disorder
      profile and ensuing function(s) may not appear in a traditional analysis of the
      evolutionary history of the protein. RESULTS: Here we present DisCons (Disorder
      Conservation), a novel pipelined tool that combines the quantification of
      sequence- and disorder conservation to classify disordered residue positions.
      According to this scheme, the most interesting categories (for functional
      purposes) are constrained disordered residues and flexible disordered residues.
      The former residues show conservation of both the sequence and the property of
      disorder and are associated mainly with specific binding functionalities (e.g.,
      short, linear motifs, SLiMs), whereas the latter class correspond to segments
      where disorder as a feature is important for function as opposed to the identity
      of the underlying sequence (e.g., entropic chains and linkers). DisCons therefore
      helps with elucidating the function(s) arising from the disordered state by
      analyzing individual proteins as well as large-scale proteomics datasets.
      CONCLUSIONS: DisCons is an openly accessible sequence analysis tool that
      identifies and highlights structurally disordered segments of proteins where the
      conformational flexibility is conserved across homologs, and therefore
      potentially functional. The tool is freely available both as a web application
      and as stand-alone source code hosted at http://pedb.vib.be/discons .

PMID- 25968232
TI  - Effects of Moderate Hyperbilirubinemia on Nutritive Swallowing and Swallowing
      Breathing Coordination in Preterm Lambs.
AB  - BACKGROUND: Hyperbilirubinemia (HB) occurs in 90% of preterm newborns. HB induces
      acute neurological disorders (somnolence, abnormal tone, feeding difficulties,
      auditory dysfunction) and alterations in respiratory control. These findings
      suggest brainstem neurotoxicity that could also affect swallowing centers.
      OBJECTIVE: To test the hypothesis that HB impairs nutritive swallowing (NS) and
      swallowing-breathing coordination. METHODS: Two groups of preterm lambs (born 14
      days prior to term), namely control (n = 6) and HB (n = 5), were studied. On day
      5 of life (D0), moderate HB (150-250 umol/l) was induced during 17 h in the HB
      group. Swallowing was assessed via recording of pharyngeal pressure and
      respiration by respiratory inductance plethysmography and pulse oximetry. The
      effect of HB on NS was assessed during standardized bottle-feeding. A second
      recording was performed 48 h after recovery from HB (D3). RESULTS: Swallows were
      less frequent (p = 0.003) and of smaller volume (p = 0.01) in HB lambs while
      swallowing frequency was decreased (p = 0.004). These differences disappeared
      after HB normalization. Swallowing-breathing coordination was impaired in HB
      lambs, with a decrease in percent time with NS burst-related apneas/hypopneas at
      D0 and D3. Simultaneously, HB lambs tended to experience more severe
      desaturations (<80%) during bottle-feeding. Finally, following bottle-feeding,
      the respiratory rate was significantly lower, along with an increased apnea
      duration in HB lambs. CONCLUSIONS: Swallowing and swallowing-breathing
      coordination are altered by acute moderate HB in preterm lambs. Decreased
      efficiency at bottle-feeding is accompanied by continuation of breathing during
      swallow bursts, which may promote lung aspiration.

PMID- 25968233
TI  - Keeping the heart empty and beating: an alternative technique to preserve
      hypertrophied hearts during valvular surgery.
AB  - INTRODUCTION: To determine whether keeping the heart empty and beating is an
      effective technique to preserve hypertrophied pig hearts, and to investigate the
      underlying mechanism. METHODS: Ten Bama Miniature pigs with hypertrophied hearts
      were divided into 2 groups (n = 5 in each group). One group underwent
      normothermic normokalemic simultaneous perfusion (NNSP). The other group was
      subjected to normothermic hypermokalemic simultaneous perfusion (NHSP) and used
      as controls. Cardiac contractive function, myocardial energy metabolism and
      myocardial perfusion were assessed using magnetic resonance imaging. Western blot
      analysis was carried out to determine the expression of Troponin I (cTnI),
      Troponin T (cTnT), SM-MHC, Casapase-3 and PARP4. TUNEL assay was used to detect
      apoptotic cardiomyocytes. RESULTS: Keeping the heart empty and beating with NNSP
      improved the preservation of contractile function in comparison with cardioplegic
      arrest using NHSP. No significant differences existed in the effects of NNSP and
      NHSP in maintaining myocardial energy metabolism. 13 % perfusion defects areas
      were found in one heart in the NHSP group, whereas none was found in all other
      hearts in both groups. The expressions of cTnI, cTnT, Casapase-3 and PARP4 in
      NHSP group were abundantly increased compared to NNSP group as measured by
      Western blotting. Conversely, the expression of SM-MHC in NHSP group was reduced
      compared with NNSP group. The number of TUNEL positive nuclei per mm(2) area was
      significantly increased in NHSP group compared with NNSP group. CONCLUSIONS:
      Keeping the heart beating with NNSP is an alternative technique to preserve
      hypertrophied hearts during valvular surgery.

PMID- 25968234
TI  - Prognostic indices for early mortality in ischaemic stroke - meta-analysis.
AB  - OBJECTIVES: Several models have been developed to predict mortality in ischaemic
      stroke. We aimed to evaluate systematically the performance of published stroke
      prognostic scores. METHODS: We searched MEDLINE and EMBASE in February 2014 for
      prognostic models (published between 2003 and 2014) used in predicting early
      mortality (<6 months) after ischaemic stroke. We evaluated discriminant ability
      of the tools through meta-analysis of the area under the curve receiver operating
      characteristic curve (AUROC) or c-statistic. We evaluated the following
      components of study validity: collection of prognostic variables, neuroimaging,
      treatment pathways and missing data. RESULTS: We identified 18 articles
      (involving 163 240 patients) reporting on the performance of prognostic models
      for mortality in ischaemic stroke, with 15 articles providing AUC for meta
      analysis. Most studies were either retrospective, or post hoc analyses of
      prospectively collected data; all but three reported validation data. The iSCORE
      had the largest number of validation cohorts (five) within our systematic review
      and showed good performance in four different countries, pooled AUC 0.84 (95% CI
      0.82-0.87). We identified other potentially useful prognostic tools that have yet
      to be as extensively validated as iSCORE - these include SOAR (2 studies, pooled
      AUC 0.79, 95% CI 0.78-0.80), GWTG (2 studies, pooled AUC 0.72, 95% CI 0.72-0.72)
      and PLAN (1 study, pooled AUC 0.85, 95% CI 0.84-0.87). CONCLUSIONS: Our meta
      analysis has identified and summarized the performance of several prognostic
      scores with modest to good predictive accuracy for early mortality in ischaemic
      stroke, with the iSCORE having the broadest evidence base.

PMID- 25968235
TI  - The chance case history of an unusual disease: mesenteric panniculitis.

PMID- 25968236
TI  - Re: Effects of subcutaneously injected Ca Cu EDTA on concentrations of Cu in
      liver, milk production and reproductive performance in New Zealand dairy cows.

PMID- 25968237
TI  - Carbamate nerve agent prophylatics exhibit distinct toxicological effects in the
      zebrafish embryo model.
AB  - Pyridostigmine bromide (PB) is an FDA-approved drug for the treatment of
      myasthenia gravis and a prophylactic pre-treatment for organophosphate nerve
      agent poisoning. Current methods for evaluating nerve agent treatments include
      enzymatic studies and mammalian models. Rapid whole animal screening tools for
      assessing the effects of nerve agent pre-treatment and post-exposure drugs
      represent an underdeveloped area of research. We used zebrafish as a model for
      acute and chronic developmental exposure to PB and two related carbamate
      acetylcholinesterase (AChE) inhibitors, neostigmine bromide (NB) and
      physostigmine (PS). Lethal doses and gross morphological phenotypes resulting
      from exposure to sub-lethal doses of these compounds were determined.
      Quantitative analyses of motility impairment and AChE enzyme inhibition were used
      to determine optimal dosing conditions for evaluation of the effects of carbamate
      exposures on neuronal development; ~50% impairment of response to startle stimuli
      and >50% inhibition of AChE activity were observed at 80 mMPB, 20 mM NB and 0.1
      mM PS. PB induced stunted somite length, but no other phenotypic effects were
      observed. In contrast, NB and PS induced more severe phenotypic morphological
      defects than PB as well as neurite outgrowth mislocalization. Additionally, NB
      induced mislocalization of nicotinic acetylcholine receptors, resulting in
      impaired synapse formation. Taken together, these data suggest that altered
      patterns of neuronal connectivity contribute to the developmental neurotoxicity
      of carbamates and demonstrate the utility of the zebrafish model for
      distinguishing subtle structure-based differential effects of AChE inhibitors,
      which include nerve agents, pesticides and drugs.

PMID- 25968238
TI  - Accurate Detection of Hepatitis B Virus G1896A Mutant by Developed Taqman-ARMS
      Followed a Strict Control System.
AB  - BACKGROUND: Hepatitis B virus (HBV) G1896A mutation was associated with HBeAg
      seronegativity and hepatitis B related acute-on-chronic liver failure. In this
      study, we developed Taqman amplification refractory mutation system (Taqman-ARMS)
      and established a strict control system to detect HBV G1896A mutant. METHODS: HBV
      viral DNA was isolated from 60 patient serum samples, and full-length HBV genome
      was cloned. Then, Taqman-ARMS was used to detect HBV G1896A mutant. RESULTS: The
      assay has the sensitivity of 1E+3 IU/ml G1896A template, and 0.1% weak population
      virus with G1896A could be found in mixtures. Total of all 60 clinical samples
      random collected were detected by Taqman-ARMS, the results were consistent with
      those by DNA sequencing. CONCLUSION: The proposed Taqman-ARMS real-time PCR
      method for the detection of G1896A mutation of HBV was rapid, simple, sensitive,
      specific, and applicable in the clinical setting.

PMID- 25968239
TI  - Genetic Regulation of Puberty Timing in Humans.
AB  - Understanding the regulation of puberty timing has relevance to developmental and
      human biology and to the pathogenesis of various diseases. Recent large-scale
      genome-wide association studies on puberty timing and adult height, body mass
      index (BMI) and central body shape provide evidence for shared biological
      mechanisms that regulate these traits. There is a substantial genetic overlap
      between age at menarche in women and BMI, with almost invariable directional
      consistency with the epidemiological associations between earlier menarche and
      higher BMI. By contrast, the genetic loci identified for age at menarche are
      largely distinct from those identified for central body shape, while alleles that
      confer earlier menarche can be associated with taller or shorter adult height.
      The findings of population-based studies on age at menarche show increasing
      relevance for other studies of rare monogenic disorders and enrich our
      understanding of the mechanisms that regulate the timing of puberty and
      reproductive function.

PMID- 25968240
TI  - Lead exposure in US worksites: A literature review and development of an
      occupational lead exposure database from the published literature.
AB  - BACKGROUND: Retrospective exposure assessment of occupational lead exposure in
      population-based studies requires historical exposure information from many
      occupations and industries. METHODS: We reviewed published US exposure monitoring
      studies to identify lead measurement data. We developed an occupational lead
      exposure database from the 175 identified papers containing 1,111 sets of lead
      concentration summary statistics (21% area air, 47% personal air, 32% blood). We
      also extracted ancillary exposure-related information, including job, industry,
      task/location, year collected, sampling strategy, control measures in place, and
      sampling and analytical methods. RESULTS: The measurements were published between
      1940 and 2010 and represented 27 2-digit standardized industry classification
      codes. The majority of the measurements were related to lead-based paint work,
      joining or cutting metal using heat, primary and secondary metal manufacturing,
      and lead acid battery manufacturing. CONCLUSIONS: This database can be used in
      future statistical analyses to characterize differences in lead exposure across
      time, jobs, and industries.

PMID- 25968242
TI  - A simple fluorescent off-on probe for the discrimination of cysteine from
      glutathione.
AB  - A simple and stable fluorescent off-on probe for discrimination of cysteine (Cys)
      from glutathione (GSH) has been developed by combining resorufin with 7
      nitrobenzofurazan. The probe, displaying distinct emission patterns for Cys and
      GSH at just one excitation wavelength, can be used for simultaneous determination
      of Cys and GSH in human plasma. 

PMID- 25968241
TI  - Augmentation of tibial plateau fractures with an injectable bone substitute:
      CERAMENTTM. Three year follow-up from a prospective study.
AB  - BACKGROUND: Reduction of tibial plateau fractures and maintain a level of well
      aligned congruent joint is key to a satisfactory clinical outcome and is
      important for the return to pre-trauma level of activity. Stable internal
      fixation support early mobility and weight bearing. The augmentation with bone
      graft substitute is often required to support the fixation to mantain reduction.
      For these reasons there has been development of novel bone graft substitutes for
      trauma applications and in particular synthetic materials based on calcium
      phosphates and/or apatite combined with calcium sulfates. Injectable bone
      substitutes can optimize the filling of irregular bone defects. The purpose of
      this study was to assess the potential of a novel injectable bone substitute
      CERAMENTTM|BONE VOID FILLER in supporting the initial reduction and preserving
      alignment of the joint surface until fracture healing. METHODS: From June 2010
      through May 2011 adult patients presenting with acute, closed and unstable tibial
      plateau fractures which required both grafting and internal fixation, were
      included in a prospective study with percutaneous or open reduction and internal
      fixation (ORIF) augmented with an injectable ceramic biphasic bone substitute
      CERAMENTTM|BONE VOID FILLER (BONESUPPORTTM, Lund, Sweden) to fill residual voids.
      Clinical follow up was performed at 1, 3, 9 and 12 months and any subsequent
      year; including radiographic analysis and Rasmussen system for knee functional
      grading. RESULTS: Twenty four patients, balanced male-to-female, with a mean age
      of 47 years, were included and followed with an average of 44 months (range 41-52
      months). Both Schatzker and Muller classifications were used and was type II or
      41-B3 in 7 patients, type III or 41-B2 in 12 patients, type IV or 41-C1 in 2
      patients and type VI or 41-C3 in 3 patients, respectively. The joint alignement
      was satisfactory and manteined within a range of 2 mm, with an average of 1.18
      mm. The mean Rasmussen knee function score was 26.5, with 14 patients having an
      excellent result and the remaining 10 with a good result. CONCLUSION: It can be
      concluded that radiological and clinical outcome was satisfactory and obtained in
      all cases without complications. This injectable novel biphasic hydroxyapatite
      and calcium sulfate ceramic material is a valuable armamentarium in the treatment
      of trauma where bone graft is required.

PMID- 25968244
TI  - Body Image in Children with Morphea: A Systematic Review.
AB  - This systematic review was conducted to evaluate the present state of body image
      research in children with morphea and the extent of body image distress in this
      population. Only five studies met inclusion criteria. Disease-related skin
      changes in children with morphea typically were associated with, at most, mild
      levels of body image distress. 

PMID- 25968245
TI  - Enveloped virus-like particle platforms: vaccines of the future?
AB  - The techniques to produce effective vaccines have evolved, and the early vaccines
      (live, inactivated, subunit...) are no longer considered as the most appropriate
      for new vaccine development. We question here what will be the future vaccines,
      and argue that virus-like particle (VLP)-based vaccines are promising candidates.
      In addition to being effective vaccines against analogous viruses from which they
      are derived, VLPs can also be used to present foreign epitopes to the immune
      system. The achievement of this strategy can be illustrated by the recent
      development of malaria candidate vaccine. We point out recent VLP-based vaccine
      developments and discuss future perspectives.

PMID- 25968246
TI  - Introductory lecture: nanoplasmonics.
AB  - Nanoplasmonics or nanoscale metal-based optics is a field of science and
      technology with a tremendously rich and colourful history. Starting with the
      early works of Michael Faraday on gold nanocolloids and optically-thin gold leaf,
      researchers have been fascinated by the unusual optical properties displayed by
      metallic nanostructures. We now can enjoy selecting from over 10 000 publications
      every year on the topic of plasmonics and the number of publications has been
      doubling about every three years since 1990. This impressive productivity can be
      attributed to the significant growth of the scientific community as plasmonics
      has spread into a myriad of new directions. With 2015 being the International
      Year of Light, it seems like a perfect moment to review some of the most notable
      accomplishments in plasmonics to date and to project where the field may be
      moving next. After discussing some of the major historical developments in the
      field, this article will analyse how the most successful plasmonics applications
      are capitalizing on five key strengths of metallic nanostructures. This
      Introductory Lecture will conclude with a brief look into the future. 

PMID- 25968247
TI  - Erratum to: A Re-evaluation and Validation of Ontogeny Functions for Cytochrome
      P450 1A2 and 3A4 Based on In Vivo Data.

PMID- 25968248
TI  - The Rhythm of Perception: Entrainment to Acoustic Rhythms Induces Subsequent
      Perceptual Oscillation.
AB  - Acoustic rhythms are pervasive in speech, music, and environmental sounds. Recent
      evidence for neural codes representing periodic information suggests that they
      may be a neural basis for the ability to detect rhythm. Further, rhythmic
      information has been found to modulate auditory-system excitability, which
      provides a potential mechanism for parsing the acoustic stream. Here, we explored
      the effects of a rhythmic stimulus on subsequent auditory perception. We found
      that a low-frequency (3 Hz), amplitude-modulated signal induces a subsequent
      oscillation of the perceptual detectability of a brief nonperiodic acoustic
      stimulus (1-kHz tone); the frequency but not the phase of the perceptual
      oscillation matches the entrained stimulus-driven rhythmic oscillation. This
      provides evidence that rhythmic contexts have a direct influence on subsequent
      auditory perception of discrete acoustic events. Rhythm coding is likely a
      fundamental feature of auditory-system design that predates the development of
      explicit human enjoyment of rhythm in music or poetry. 

PMID- 25968249
TI  - Serum galectin-3 levels in children with chronic hepatitis B infection and
      inactive hepatitis B carriers.
AB  - BACKGROUND: Chronic hepatitis B virus (HBV) infection is common worldwide. Follow
      up of patients by the use of non-invasive techniques may be valuable in clinical
      practice. The aim of this study was to investigate serum galectin-3 (GAL-3)
      levels for monitoring disease status in children with chronic HBV infection.
      MATERIAL/METHODS: Thirty-two patients with chronic hepatitis B (CHB), 30 inactive
      HBV carrier patients, and 30 matched healthy controls were enrolled in the study.
      We performed basic laboratory tests: serum glucose, albumin, alanine
      aminotransferase (ALT), aspartate aminotransferase, gamma-glutamyl transferase
      (GGT), total bilirubin, prothrombin time, and activated partial thromboplastin
      time. In addition, serum GAL-3 levels were measured by ELISA technique. RESULTS:
      Significantly higher serum GAL-3 levels (16.5+/-3.6, 1.1+/-0.3, 0.7+/-0.5 ng/ml,
      respectively, p<0.001) and ALT levels (80.2+/-30.6, 26.8+/-12.6, 28.1+/-4.4 IU/L,
      respectively, p<0.001) were found in the CHB group compared with the inactive
      carriers and the control groups. There were no significant differences in ALT
      levels and GAL-3 levels or between inactive HBV carriers and the control groups
      (p>0.05, for each). Significantly higher GGT levels were found in the CHB group
      (51.3+/-27.5 IU/L) compared with the inactive HBV carriers (35.7+/-10.1 IU/L) and
      the control group (31.3+/-9.5 IU/L) (p<0.001, and p=0.004, respectively). A
      significant correlation was found between GAL-3 and ALT levels in the CHB group
      (r=0.82, p<0.001). CONCLUSIONS: Our results suggest that serum GAL-3 level may be
      a beneficial indicator of chronicity in hepatitis B infection in children.

PMID- 25968250
TI  - Titanium carbenoid-mediated cyclopropanation of allylic alcohols: selectivity and
      mechanism.
AB  - A new method for the chemo- and stereoselective conversion of allylic alcohols
      into the corresponding cyclopropane derivatives has been developed. The
      cyclopropanation reaction was carried out with an unprecedented titanium
      carbenoid generated in situ from Nugent's reagent, manganese and methylene
      diiodide. The reaction involving the participation of an allylic hydroxyl group,
      proceeded with conservation of the alkene geometry and in a high diastereomeric
      excess. The scope, limitations and mechanism of this metal-catalysed reaction are
      discussed. 

PMID- 25968251
TI  - Prevalence of auditory hallucinations in Norwegian adolescents: results from a
      population-based study.
AB  - Knowing the prevalence and characteristics of auditory verbal hallucinations
      (AVH) in adolescents is important for estimations of need for mental health care
      and assessment of psychosis risk. In this report we assess the prevalence of AVH
      in a population-based sample of 16-19 years old Norwegian adolescents (n = 9,646,
      46.4% male) using two items assessing AVH (from the extended Launay-Slade
      Hallucination Scale). The prevalence of hearing a voice speaking thoughts aloud
      was 10.6%. The prevalence of being troubled by voices was 5.3%, showing that
      negative emotionality about AVH is less frequent than the experience of hearing
      voices. Female respondents had slightly increased risk for being troubled by
      voices than males (odds ratio = 1.3), while age did not modulate prevalence. This
      AVH prevalence is in line with earlier reports in smaller samples of adolescents
      and indicates that AVH are not uncommon in this period of life. Further
      longitudinal studies are needed to investigate the value of AVH in predicting
      psychiatric disorder. 

PMID- 25968252
TI  - Mobility and sulfidization of heavy metals in sediments of a shallow eutrophic
      lake, Lake Taihu, China.
AB  - The technique of DGT (diffusive gradients in thin films) using three diffusive
      gel thicknesses was applied to estimate the mobility and bioavailability of heavy
      metals in sediments and porewater of Lake Taihu, China. The DGT results showed
      significantly positive correlations between Co, Pb, Cd and Mn, and Ni and Fe
      concentrations in porewater. Cu and Zn showed a significantly negative
      correlation with Mn, due to Cu combination with carbonates and Zn derived from
      agricultural pollution, respectively. The rank order of average concentrations of
      Co, Ni and Cd at each station was DGT1.92>DGT0.78>DGT0.39, suggesting stronger
      resupply from sediments to porewater when using thicker diffusive gels. Comparing
      centrifugation and DGT measurements, Co, Ni and Cd are highly labile; Mn and Fe
      are moderately labile; and Cu, Zn and Pb are slightly labile. The variations of
      AVS concentrations in sediment cores indicate that metal sulfides in deeper
      layers are easily diffused into surface sediments. 

PMID- 25968253
TI  - Predicting the aquatic risk of realistic pesticide mixtures to species
      assemblages in Portuguese river basins.
AB  - Although pesticide regulatory tools are mainly based on individual substances,
      aquatic ecosystems are usually exposed to multiple pesticides from their use on
      the variety of crops within the catchment of a river. This study estimated the
      impact of measured pesticide mixtures in surface waters from 2002 and 2008 within
      three important Portuguese river basins ('Mondego', 'Sado' and 'Tejo') on primary
      producers, arthropods and fish by toxic pressure calculation. Species sensitivity
      distributions (SSDs), in combination with mixture toxicity models, were applied.
      Considering the differences in the responses of the taxonomic groups as well as
      in the pesticide exposures that these organisms experience, variable acute multi
      substance potentially affected fractions (msPAFs) were obtained. The median msPAF
      for primary producers and arthropods in surface waters of all river basins
      exceeded 5%, the cut-off value used in the prospective SSD approach for deriving
      individual environmental quality standards. A ranking procedure identified
      various photosystem II inhibiting herbicides, with oxadiazon having the
      relatively largest toxic effects on primary producers, while the organophosphorus
      insecticides, chlorfenvinphos and chlorpyrifos, and the organochloride endosulfan
      had the largest effects on arthropods and fish, respectively. These results
      ensure compliance with European legislation with regard to ecological risk
      assessment and management of pesticides in surface waters. 

PMID- 25968254
TI  - Treatment and resource recovery from inorganic fluoride-containing waste produced
      by the pesticide industry.
AB  - The rapid development of the fluorinated pesticide industry has produced a large
      amount of fluorine-containing hazardous waste, especially inorganic fluoride
      containing waste (IFCW). A two-step process, including extraction and recovery,
      was developed to recover fluorine as synthetic cryolite from IFCW produced by the
      pesticide industry. The optimum conditions for extraction were found to be a
      temperature of 75 degrees C, an initial pH (pHi) of 12, a 4-hr incubation time
      and a liquid-to-solid ratio of 40mL/g; these conditions resulted in a fluorine
      extraction ratio of 99.0%. The effects of pH and the F/Al molar ratio on fluorine
      recovery and the compositional, mineralogical and morphological characteristics
      of the cryolite products were investigated. Field-emission scanning electron
      microscopy of recovered precipitates showed changes in morphology with the F/Al
      molar ratio. Coupling Fourier transform and infrared spectroscopy, X-ray
      diffraction indicated that the formation of AlF6(3-) was restricted as increasing
      pH. Both the amount of fluorine recovered and the quality of the cryolite were
      optimized at initial pH=3 and a F/Al molar ratio 5.75. This study proposed a
      reliable and environmentally friendly method for the treatment of fluoride
      containing wastes, which could be suitable for industrial applications. 

PMID- 25968255
TI  - Effects of water regime, crop residues, and application rates on control of
      Fusarium oxysporum f. sp. cubense.
AB  - Biological soil disinfestation is an effective method to control soil-borne
      disease by flooding and incorporating with organic amendments, but field
      conditions and resources sometimes limited its practical application. A
      laboratory experiment was conducted to develop practice guidelines on controlling
      Fusarium wilt, a widespread banana disease caused by Fusarium oxysporum f. sp.
      cubense (FOC). FOC infested soil incorporated with rice or maize straw at rates
      of 1.5 tons/ha and 3.0 tons/ha was incubated under flooded or water-saturated
      (100% water holding capacity) conditions at 30 degrees C for 30 days. Results
      showed that FOC populations in the soils incorporated with either rice or maize
      straw rapidly reduced more than 90% in the first 15 days and then fluctuated till
      the end of incubation, while flooding alone without organic amendment reduced FOC
      populations slightly. The rapid and dramatic decrease of redox potential (down to
      -350 mV) in straw-amended treatments implied that both anaerobic condition and
      strongly reductive soil condition would contribute to pathogen inactivation.
      Water-saturation combined with straw amendments had the comparable effects on
      reduction of FOC, indicating that flooding was not indispensable for inactivating
      FOC. There was no significant difference in the reduction of FOC observed in the
      straw amendments at between 1.5 and 3 tons/ha. Therefore, incorporating soil with
      straw (rice or maize straw) at a rate of 3.0 tons/ha under 100% water holding
      capacity or 1.5 tons/ha under flooding, would effectively alleviate banana
      Fusarium wilt caused by FOC after 15-day treating under 30 degrees C.

PMID- 25968256
TI  - Microcystis aeruginosa/Pseudomonas pseudoalcaligenes interaction effects on off
      flavors in algae/bacteria co-culture system under different temperatures.
AB  - We conducted an experiment to study the interaction effects of Microcystis
      aeruginosa and Pseudomonas pseudoalcaligenes on off-flavors in an algae/bacteria
      co-culture system at three temperatures (24, 28 and 32 degrees C). Gas
      chromatography-mass spectrometry was applied to measure off-flavor compounds
      dimethyl sulfide (DMS), dimethyl trisulfide (DMTS), 2-methylisoborneol, geosmin
      (GEO) and beta-cyclocitral. During the lag phase of co-cultured M. aeruginosa
      (first 15days), P. pseudoalcaligenes significantly increased the production of
      DMS, DMTS and beta-cyclocitral at all three temperatures. In the exponential
      phase of co-cultured M. aeruginosa (after 15days), M. aeruginosa became the main
      factor on off-flavors in the co-culture system, and beta-cyclocitral turned to
      the highest off-flavor compound. These results also indicated that DMS, DMTS and
      beta-cyclocitral were the main off-flavor compounds in our M. aeruginosa/P.
      pseudoalcaligenes co-culture system. Univariate analysis was applied to
      investigate the effects of M. aeruginosa and P. pseudoalcaligenes on the
      production of off-flavors. The results demonstrated that both M. aeruginosa and
      P. pseudoalcaligenes could increase the production of DMS and DMTS, while beta
      cyclocitral was mainly determined by M. aeruginosa. Our results also provide some
      insights into understanding the relationship between cyanobacteria and
      heterotrophic bacteria. 

PMID- 25968257
TI  - Greenhouse gas emission and its potential mitigation process from the waste
      sector in a large-scale exhibition.
AB  - As one of the largest human activities, World Expo is an important source of
      anthropogenic Greenhouse Gas emission (GHG), and the GHG emission and other
      environmental impacts of the Expo Shanghai 2010, where around 59,397 tons of
      waste was generated during 184 Expo running days, were assessed by life cycle
      assessment (LCA). Two scenarios, i.e., the actual and expected figures of the
      waste sector, were assessed and compared, and 124.01 kg CO2-equivalent (CO2-eq.),
      4.43 kg SO2-eq., 4.88 kg NO3--eq., and 3509 m3 water per ton tourist waste were
      found to be released in terms of global warming (GW), acidification (AC),
      nutrient enrichment (NE) and spoiled groundwater resources (SGWR), respectively.
      The total GHG emission was around 3499 ton CO2-eq. from the waste sector in Expo
      Park, among which 86.47% was generated during the waste landfilling at the rate
      of 107.24 kg CO2-eq., and CH4, CO and other hydrocarbons (HC) were the main
      contributors. If the waste sorting process had been implemented according to the
      plan scenario, around 497 ton CO2-eq. savings could have been attained. Unlike
      municipal solid waste, with more organic matter content, an incineration plant is
      more suitable for tourist waste disposal due to its high heating value, from the
      GHG reduction perspective.

PMID- 25968258
TI  - Role of secondary aerosols in haze formation in summer in the Megacity Beijing.
AB  - A field experiment from 18 August to 8 September 2006 in Beijing, China, was
      carried out. A hazy day was defined as visibility<l0 km and RH (relative
      humidity)<90%. Four haze episodes, which accounted for ~60% of the time during
      the whole campaign, were characterized by increases of SNA (sulfate, nitrate, and
      ammonium) and SOA (secondary organic aerosol) concentrations. The average values
      with standard deviation of SO4(2-), NO3-, NH4+ and SOA were 49.8 (+/-31.6), 31.4
      (+/-22.3), 25.8 (+/-16.6) and 8.9 (+/-4.1)MUg/m3, respectively, during the haze
      episodes, which were 4.3, 3.4, 4.1, and 1.7 times those in the non-haze days. The
      SO4(2-), NO3-, NH4+, and SOA accounted for 15.8%, 8.8%, 7.3%, and 6.0% of the
      total mass concentration of PM10 during the non-haze days. The respective
      contributions of SNA species to PM10 rose to about 27.2%, 15.9%, and 13.9% during
      the haze days, while the contributions of SOA maintained the same level with a
      slight decrease to about 4.9%. The observed mass concentrations of SNA and SOA
      increased with the increase of PM10 mass concentration, however, the rate of
      increase of SNA was much faster than that of the SOA. The SOR (sulfur oxidation
      ratio) and NOR (nitrogen oxidation ratio) increased from non-haze days to hazy
      days, and increased with the increase of RH. High concentrations of aerosols and
      water vapor favored the conversion of SO2 to SO4(2-) and NO2 to NO3-, which
      accelerated the accumulation of the aerosols and resulted in the formation of
      haze in Beijing.

PMID- 25968259
TI  - Remediation effect of compost on soluble mercury transfer in a crop of Phaseolus
      vulgaris.
AB  - We studied the dynamics of mercury (Hg) transfer in Phaseolus vulgaris plants
      grown in soil with Hg-doped compost at the maximum levels permitted by Colombian
      law on organic amendments. Quantitative evaluation of transfer was made in
      different plant organs: roots, stem, leaves, pods and seeds. Matrix effect was
      determined in doped soil assays, using soil with and without addition of compost.
      Results showed that the use of organic matter reduced Hg transfer to the plant
      and the amount transferred was differentially distributed to the organs. We
      observed an inverse relationship between concentration and distance from the body
      to the root. It was evident that transfer was mediated by quantitative factors;
      the greater the presence of mercury in soil, the larger the amount that will be
      transferred. Results also indicate the remedial effect of compost and the
      presence of a barrier, at the root level, against mercury translocation to the
      plant aerial parts. 

PMID- 25968260
TI  - Enhanced U(VI) bioreduction by alginate-immobilized uranium-reducing bacteria in
      the presence of carbon nanotubes and anthraquinone-2,6-disulfonate.
AB  - Uranium-reducing bacteria were immobilized with sodium alginate, anthraquinone
      2,6-disulfonate (AQDS), and carbon nanotubes (CNTs). The effects of different
      AQDS-CNTs contents, U(IV) concentrations, and metal ions on U(IV) reduction by
      immobilized beads were examined. Over 97.5% U(VI) (20 mg/L) was removed in 8 hr
      when the beads were added to 0.7% AQDS-CNTs, which was higher than that without
      AQDS-CNTs. This result may be attributed to the enhanced electron transfer by
      AQDS and CNTs. The reduction of U(VI) occurred at initial U(VI) concentrations of
      10 to 100 mg/L and increased with increasing AQDS-CNT content from 0.1% to 1%.
      The presence of Fe(III), Cu(II) and Mn(II) slightly increased U(VI) reduction,
      whereas Cr(VI), Ni(II), Pb(II), and Zn(II) significantly inhibited U(VI)
      reduction. After eight successive incubation-washing cycles or 8 hr of retention
      time (HRT) for 48 hr of continuous operation, the removal efficiency of uranium
      was above 90% and 92%, respectively. The results indicate that the AQDS
      CNT/AL/cell beads are suitable for the treatment of uranium-containing
      wastewaters.

PMID- 25968261
TI  - NH3-SCR denitration catalyst performance over vanadium-titanium with the addition
      of Ce and Sb.
AB  - Selective catalytic reduction technology using NH3 as a reducing agent (NH3-SCR)
      is an effective control method to remove nitrogen oxides. TiO2-supported vanadium
      oxide catalysts with different levels of Ce and Sb modification were prepared by
      an impregnation method and were characterized by X-ray diffractometer (XRD),
      Brunauer-Emmett-Teller (BET), Transmission electron microscopy (TEM), Fourier
      transform infrared spectroscopy (FT-IR), UV-Vis diffuse reflectance spectroscopy
      (UV-Vis DRS), Raman and Hydrogen temperature-programmed reduction (H2-TPR). The
      catalytic activities of V5CexSby/TiO2 catalysts for denitration were investigated
      in a fixed bed flow microreactor. The results showed that cerium, vanadium and
      antimony oxide as the active components were well dispersed on TiO2, and the
      catalysts exhibited a large number of d-d electronic transitions, which were
      helpful to strengthen SCR reactivity. The V5CexSby/TiO2 catalysts exhibited a
      good low temperature NH3-SCR catalytic activity. In the temperature range of 210
      to 400 degrees C, the V5CexSby/TiO2 catalysts gave NO conversion rates above 90%.
      For the best V5Ce35Sb2/TiO2 catalyst, at a reaction temperature of 210 degrees C,
      the NO conversion rate had already reached 90%. The catalysts had different
      catalytic activity with different Ce loadings. With the increase of Ce loading,
      the NO conversion rate also increased. 

PMID- 25968262
TI  - Phosphate removal from domestic wastewater using thermally modified steel slag.
AB  - This study was performed to investigate the removal of phosphate from domestic
      wastewater using a modified steel slag as the adsorbent. The adsorption effects
      of alkalinity, salt, water, and thermal modification were investigated. The
      results showed that thermal activation at 800 degrees C for 1 hr was the optimum
      operation to improve the adsorption capacity. The adsorption process of the
      thermally modified slag was well described by the Elovich kinetic model and the
      Langmuir isotherm model. The maximum adsorption capacity calculated from the
      Langmuir model reached 13.62 mg/g. Scanning electron microscopy indicated that
      the surface of the modified slag was cracked and that the texture became loose
      after heating. The surface area and pore volume did not change after thermal
      modification. In the treatment of domestic wastewater, the modified slag bed
      (35.5 kg) removed phosphate effectively and operated for 158 days until the
      effluent P rose above the limit concentration of 0.5 mg/L. The phosphate
      fractionation method, which is often applied in soil research, was used to
      analyze the phosphate adsorption behavior in the slag bed. The analysis revealed
      that the total contents of various Ca-P forms accounted for 81.4%-91.1%, i.e.,
      Ca10-P 50.6%-65.1%, Ca8-P 17.8%-25.0%, and Ca2-P 4.66%-9.20%. The forms of Al-P,
      Fe-P, and O-P accounted for only 8.9%-18.6%. The formation of Ca10-P precipitates
      was considered to be the main mechanism of phosphate removal in the thermally
      modified slag bed.

PMID- 25968263
TI  - Acid-catalyzed heterogeneous reaction of 3-methyl-2-buten-1-ol with hydrogen
      peroxide.
AB  - Acid-catalyzed heterogeneous oxidation with hydrogen peroxide (H2O2) has been
      suggested to be a potential pathway for secondary organic aerosol (SOA) formation
      from isoprene and its oxidation products. However, knowledge of the chemical
      mechanism and kinetics for this process is still incomplete. 3-Methyl-2-buten-1
      ol (MBO321), an aliphatic alcohol structurally similar to isoprene, is emitted by
      pine forests and widely used in the manufacturing industries. Herein the uptake
      of MBO321 into H2SO4-H2O2 mixed solution was investigated using a flow-tube
      reactor coupled to a mass spectrometer. The reactive uptake coefficients (gamma)
      were acquired for the first time and were found to increase rapidly with
      increasing acid concentration. Corresponding aqueous-phase reactions were
      performed to further study the mechanism of this acid-catalyzed reaction. MBO321
      could convert to 2-methyl-3-buten-2-ol (MBO232) and yield isoprene in acidic
      media. Organic hydroperoxides (ROOHs) were found to be generated through the acid
      catalyzed route, which could undergo a rearrangement reaction and result in the
      formation of acetone and acetaldehyde. Organosulfates, which have been proposed
      to be SOA tracer compounds in the atmosphere, were also produced during the
      oxidation process. These results suggest that the heterogeneous acid-catalyzed
      reaction of MBO321 with H2O2 may contribute to SOA mass under certain atmospheric
      conditions. 

PMID- 25968264
TI  - IKK inhibition prevents PM2.5-exacerbated cardiac injury in mice with type 2
      diabetes.
AB  - Epidemiological studies have found that individuals with diabetes mellitus (DM)
      display an increased susceptibility for adverse cardiovascular outcomes when
      exposed to air pollution. This study was conducted to explore the potential
      mechanism linking ambient fine particles (PM2.5) and heart injury in a Type 2 DM
      (T2DM) animal model. The KKay mouse, an animal model of T2DM, was exposed to
      concentrated ambient PM2.5 or filtered air for 8 weeks via a versatile aerosol
      exposure and concentrator system. Simultaneously, an inhibitor of IkappaB kinase
      2 (IKK-a) (IMD-0354), which is a blocker of nuclear factor kappaB (NF-kappaB)
      nuclear translocation, was administrated by intracerebroventricular injection
      (ICV) to regulate the NF-eB pathway. The results showed that ambient PM2.5
      induced the increase of, NF-eB, cyclooxygenase-2 (COX-2) and mitogen activated
      protein kinase (MAPK) expression in cardiac tissue, and that IMD-0354 could
      alleviate the inflammatory injury. The results suggested that the NF-eB pathway
      plays an important role in mediating the PM2.5-induced cardiovascular injury in
      the T2DM model. Inhibiting NFkappaB may be a therapeutic option in air-pollution
      exacerbated cardiovascular injury in diabetes mellitus.

PMID- 25968265
TI  - New generation Amberlite XAD resin for the removal of metal ions: A review.
AB  - The direct determination of toxic metal ions, in environmental samples, is
      difficult because of the latter's presence in trace concentration in association
      with complex matrices, thereby leading to insufficient sensitivity and
      selectivity of the methods used. The simultaneous removal of the matrix and
      preconcentration of the metal ions, through solid phase extraction, serves as the
      promising solution. The mechanism involved in solid phase extraction (SPE)
      depends on the nature of the sorbent and analyte. Thus, SPE is carried out by
      means of adsorption, ion exchange, chelation, ion pair formation, and so forth.
      As polymeric supports, the commercially available Amberlite resins have been
      found very promising for designing chelating matrices due to its good physical
      and chemical properties such as porosity, high surface area, durability and
      purity. This review presents an overview of the various works done on the
      modification of Amberlite XAD resins with the objective of making it an efficient
      sorbent. The methods of modifications which are generally based on simple
      impregnation, sorption as chelates and chemical bonding have been discussed. The
      reported results, including the preconcentration limit, the detection limit,
      sorption capacity, preconcentration factors etc., have been reproduced. 

PMID- 25968266
TI  - Effects of aeration method and aeration rate on greenhouse gas emissions during
      composting of pig feces in pilot scale.
AB  - The aim of this study was to uncover ways to mitigate greenhouse gas (GHG)
      emissions and reduce energy consumption during the composting process. We
      assessed the effects of different aeration rates (0, 0.18, 0.36, and 0.54 L/(kg
      dry matter (dm).min)) and methods (continuous and intermittent) on GHG emissions.
      Pig feces and corn stalks were mixed at a ratio of 7:1. The composting process
      lasted for 10 weeks, and the compost was turned approximately every 2 weeks.
      Results showed that both aeration rate and method significantly affected GHG
      emissions. Higher aeration rates increased NH3 and N2O losses, but reduced CH4
      emissions. The exception is that the CH4 emission of the passive aeration
      treatment was lower than that of the low aeration rate treatment. Without forced
      aeration, the CH4 diffusion rates in the center of the piles were very low and
      part of the CH4 was oxidized in the surface layer. Intermittent aeration reduced
      NH3 and CH4 losses, but significantly increased N2O production during the
      maturing periods. Intermittent aeration increased the
      nitrification/denitrification alternation and thus enhanced the N2O production.
      Forced aeration treatments had higher GHG emission rates than the passive
      aeration treatment. Forced aeration accelerated the maturing process, but could
      not improve the quality of the end product. Compared with continuous aeration,
      intermittent aeration could increase the O2 supply efficiency and reduced the
      total GHG emission by 17.8%, and this reduction increased to 47.4% when
      composting was ended after 36 days.

PMID- 25968267
TI  - Two-year measurements of surface ozone at Dangxiong, a remote highland site in
      the Tibetan Plateau.
AB  - Measurements of surface O3 and carbon monoxide (CO) were made from September 2009
      to August 2011 at Dangxiong (30.48 degrees N, 91.10 degrees E, 4187 m a.s.l.), a
      remote highland site in a southern valley of the Nyainqentanglha Mountains in the
      Tibetan Plateau, China. The monthly mean O3 mixing ratio ranged from 29.1 to 51.4
      ppb, with an average of 38.5 ppb, and the maximum value was observed in May. The
      average diurnal cycle of O3 concentration showed a minimum in early morning and a
      maximum in the afternoon, with a broader "high platform" from the late morning to
      the late afternoon, and resembled that of surface wind speed. The concentration
      of surface O3 was highly significantly correlated with tropospheric column O3
      over the regions surrounding Dangxiong and with that of surface O3 observed at a
      site north of the Nyainqentanglha Mountains, suggesting a good regional
      representativeness of surface O3 at Dangxiong. In the afternoon when stronger
      winds blew, surface air showed distinct features of free-atmospheric air, with
      higher O3, lower CO, and lower relative humidity (RH). The negative O3-CO and O3
      RH correlations in most months indicate a significant influence of air masses
      from the free troposphere. Trajectory analysis suggests that air masses
      originating from the south of the site make a negative net contribution to
      surface O3 and a positive contribution to CO and humidity, and those from the
      northwest sector contribute conversely to the respective quantities.

PMID- 25968268
TI  - Synergistic effects of particulate matter (PM10) and SO2 on human non-small cell
      lung cancer A549 via ROS-mediated NF-kappaB activation.
AB  - Since a real atmospheric scenario usually represents a system involving multiple
      pollutants, air pollution studies typically focused on describing adverse effects
      associated with exposure to individual pollutants cannot reflect actual health
      risk. Particulate matter (PM10) and sulfur dioxide (SO2) are two major pollutants
      derived from coal combustion processes and co-existing in coal-smoke air
      pollution, but their potentially synergistic toxicity remains elusive thus far.
      In this study, we investigated the cytotoxic responses of PM10 and SO2, singly
      and in binary mixtures, using human non-small cell lung cancer A549 cells,
      followed by clarifying the possible mechanisms for their interaction. The results
      indicated that the concomitant treatment of PM10 and SO2 at low concentrations
      led to synergistic injury in terms of cell survival and apoptosis occurrence,
      while PM10 and SO2 alone at the same concentrations did not cause damage to the
      cells. Also, radical oxygen species (ROS) production followed by nuclear factor
      kappa B (NF-kappaB) activation was involved in the above synergistic
      cytotoxicity, which was confirmed by the repression of the actions by an ROS
      inhibitor (NAC). This implies that assessment of health risk should consider the
      interactions between ambient PM and gaseous copollutants. 

PMID- 25968269
TI  - Adsorption and biodegradation of three selected endocrine disrupting chemicals in
      river-based artificial groundwater recharge with reclaimed municipal wastewater.
AB  - Endocrine disrupting chemical (EDC) pollution in river-based artificial
      groundwater recharge using reclaimed municipal wastewater poses a potential
      threat to groundwater-based drinking water supplies in Beijing, China. Lab-scale
      leaching column experiments simulating recharge were conducted to study the
      adsorption, biodegradation, and transport characteristics of three selected EDCs:
      17beta-estradiol (E2), 17alpha-ethinylestradiol (EE2) and bisphenol A (BPA). The
      three recharge columns were operated under the conditions of continual
      sterilization recharge (CSR), continual recharge (CR), and wetting and drying
      alternative recharge (WDAR). The results showed that the attenuation effect of
      the EDCs was in the order of WDAR>CR>CSR system and E2>EE2>BPA, which followed
      first-order kinetics. The EDC attenuation rate constants were 0.0783, 0.0505, and
      0.0479 m(-1) for E2, EE2 and BPA in the CR system, respectively. The removal
      rates of E2, EE2, and BPA in the CR system were 98%, 96% and 92%, which mainly
      depended on biodegradation and were affected by water temperature. In the CR
      system, the concentrations of BPA, EE2, and E2 in soil were 4, 6 and 10 times
      higher than in the WDAR system, respectively. According to the DGGE fingerprints,
      the bacterial community in the bottom layer was more diverse than in the upper
      layer, which was related to the EDC concentrations in the water-soil system. The
      dominant group was found to be proteobacteria, including Betaproteobacteria and
      Alphaproteobacteria, suggesting that these microbes might play an important role
      in EDC degradation.

PMID- 25968270
TI  - Co-adsorption of gaseous benzene, toluene, ethylbenzene, m-xylene (BTEX) and SO2
      on recyclable Fe3O4 nanoparticles at 0-101% relative humidities.
AB  - We herein used Fe3O4 nanoparticles (NPs) as an adsorption interface for the
      concurrent removal of gaseous benzene, toluene, ethylbenzene and m-xylene (BTEX)
      and sulfur dioxide (SO2), at different relative humidities (RH). X-ray
      diffraction, Brunauer-Emmett-Teller, and transmission electron microscopy were
      deployed for nanoparticle surface characterization. Mono-dispersed Fe3O4
      (Fe2O3.FeO) NPs synthesized with oleic acid (OA) as surfactant, and uncoated poly
      dispersed Fe3O4 NPs demonstrated comparable removal efficiencies. Adsorption
      experiments of BTEX on NPs were measured using gas chromatography equipped with
      flame ionization detection, which indicated high removal efficiencies (up to
      (95+/-2)%) under dry conditions. The humidity effect and competitive adsorption
      were investigated using toluene as a model compound. It was observed that the
      removal efficiencies decreased as a function of the increase in RH, yet, under
      our experimental conditions, we observed (40+/-4)% toluene removal at
      supersaturation for Fe3O4 NPs, and toluene removal of (83+/-4)% to (59+/-6)%, for
      OA-Fe3O4 NPs. In the presence of SO2, the toluene uptake was reduced under dry
      conditions to (89+/-2)% and (75+/-1)% for the uncoated and coated NPs,
      respectively, depicting competitive adsorption. At RH>100%, competitive
      adsorption reduced the removal efficiency to (27+/-1)% for uncoated NPs whereas
      OA-Fe3O4 NPs exhibited moderate efficiency loss of (55+/-2)% at supersaturation.
      Results point to heterogeneous water coverage on the NP surface. The magnetic
      property of magnetite facilitated the recovery of both types of NPs, without the
      loss in efficiency when recycled and reused. 

PMID- 25968271
TI  - Weak magnetic field accelerates chromate removal by zero-valent iron.
AB  - Weak magnetic field (WMF) was employed to improve the removal of Cr(VI) by zero
      valent iron (ZVI) for the first time. The removal rate of Cr(VI) was elevated by
      a factor of 1.12-5.89 due to the application of a WMF, and the WMF-induced
      improvement was more remarkable at higher Cr(VI) concentration and higher pH.
      Fe2+ was not detected until Cr(VI) was exhausted, and there was a positive
      correlation between the WMF-induced promotion factor of Cr(VI) removal rate and
      that of Fe2+ release rate in the absence of Cr(VI) at pH4.0-5.5. These phenomena
      imply that ZVI corrosion with Fe2+ release was the limiting step in the process
      of Cr(VI) removal. The superimposed WMF had negligible influence on the apparent
      activation energy of Cr(VI) removal by ZVI, indicating that WMF accelerated
      Cr(VI) removal by ZVI but did not change the mechanism. The passive layer formed
      with WMF was much more porous than without WMF, thereby facilitating mass
      transport. Therefore, WMF could accelerate ZVI corrosion and alleviate the
      detrimental effects of the passive layer, resulting in more rapid removal of
      Cr(VI) by ZVI. Exploiting the magnetic memory of ZVI, a two-stage process
      consisting of a small reactor with WMF for ZVI magnetization and a large reactor
      for removing contaminants by magnetized ZVI can be employed as a new method of
      ZVI-mediated remediation.

PMID- 25968272
TI  - Trace metal concentrations in hairs of three bat species from an urbanized area
      in Germany.
AB  - Metal-contaminated soils and sediments are widespread in urbanized areas due to
      atmospheric deposition close to emission sources. These metals are bio-available
      for organisms, e.g., insects, and accumulate in food chains of insectivorous
      mammals. Especially bats, which live in urban regions and ingest large amounts of
      food relative to their body mass, are at risk of being poisoned due to the
      accumulation of trace metals. To determine species-specific trace metal contents
      in bats from urban environments, hair samples were analyzed by ICP-OES. Observed
      trace metal concentrations were related to species-specific foraging habitat,
      prey spectrum and degree of synanthropy. The species studied were Pipistrellus
      pipistrellus, Myotis daubentonii and Nyctalus noctula. P. pipistrellus showed the
      highest concentrations of lead and zinc and slightly higher concentrations of
      cadmium than the other two species, which was related to its high degree of
      synanthropy with foraging habitat mostly located in cities. In contrast, N.
      noctula displayed the highest contents of manganese and copper. The reason might
      be found in its prey spectrum, as N. noctula feeds mainly on beetles that are
      caught in cultured areas. Trace metal concentrations determined in hair samples
      of M. daubentonii ranged between the values of P. pipistrellus and N. noctula,
      probably reflecting an intermediate level of synanthropy. Positive correlations
      were observed between the concentrations of cadmium and lead and those of
      manganese and copper. Hair samples from bats are suitable monitoring tools to
      study trace metal exposure and can be used to determine differences in trace
      metal levels between species. 

PMID- 25968274
TI  - Mobility of toxic metals in sediments: Assessing methods and controlling factors.

PMID- 25968273
TI  - Preparation and characterization of Pd/Fe bimetallic nanoparticles immobilized on
      Al2O3/PVDF membrane: Parameter optimization and dechlorination of dichloroacetic
      acid.
AB  - Using a liquid-solid phase inversion method, a hybrid matrix poly(vinylidene
      fluoride) (PVDF) membrane was prepared with alumina (Al2O3) nanoparticle
      addition. Pd/Fe nanoparticles (NPs) were successfully immobilized on the
      Al2O3/PVDF membrane, which was characterized by Scanning Electron Microscopy
      (SEM) and Transmission Electron Microscopy (TEM). The micrographs showed that the
      Pd/Fe NPs were dispersed homogeneously. Several important experimental parameters
      were optimized, including the mechanical properties, contact angle and surface
      area of Al2O3/PVDF composite membranes with different Al2O3 contents. At the same
      time, the ferrous ion concentration and the effect of hydrophilization were
      studied. The results showed that the modified Al2O3/PVDF membrane functioned well
      as a support. The Al2O3/PVDF membrane with immobilized Pd/Fe NPs exhibited high
      efficiency in terms of dichloroacetic acid (DCAA) dechlorination. Additionally, a
      reaction pathway for DCAA dechlorination by Pd/Fe NPs immobilized on the
      Al2O3/PVDF membrane system was proposed. 

PMID- 25968275
TI  - Genotoxic effects of microcystins mediated by nitric oxide and mitochondria.

PMID- 25968276
TI  - Development of database of real-world diesel vehicle emission factors for China.
AB  - A database of real-world diesel vehicle emission factors, based on type and
      technology, has been developed following tests on more than 300 diesel vehicles
      in China using a portable emission measurement system. The database provides
      better understanding of diesel vehicle emissions under actual driving conditions.
      We found that although new regulations have reduced real-world emission levels of
      diesel trucks and buses significantly for most pollutants in China, NOx emissions
      have been inadequately controlled by the current standards, especially for diesel
      buses, because of bad driving conditions in the real world. We also compared the
      emission factors in the database with those calculated by emission factor models
      and used in inventory studies. The emission factors derived from COPERT (Computer
      Programmer to calculate Emissions from Road Transport) and MOBILE may both
      underestimate real emission factors, whereas the updated COPERT and PART5
      (Highway Vehicle Particulate Emission Modeling Software) models may overestimate
      emission factors in China. Real-world measurement results and emission factors
      used in recent emission inventory studies are inconsistent, which has led to
      inaccurate estimates of emissions from diesel trucks and buses over recent years.
      This suggests that emission factors derived from European or US-based models will
      not truly represent real-world emissions in China. Therefore, it is useful and
      necessary to conduct systematic real-world measurements of vehicle emissions in
      China in order to obtain the optimum inputs for emission inventory models. 

PMID- 25968277
TI  - Anoxic degradation of nitrogenous heterocyclic compounds by activated sludge and
      their active sites.
AB  - The potential for degradation of five nitrogenous heterocyclic compounds (NHCs),
      i.e., imidazole, pyridine, indole, quinoline, and carbazole, was investigated
      under anoxic conditions with acclimated activated sludge. Results showed that
      NHCs with initial concentration of 50 mg/L could be completely degraded within 60
      hr. The degradation of five NHCs was dependent upon the chemical structures with
      the following sequence: imidazole>pyridine>indole>quinoline>carbazole in terms of
      their degradation rates. Quantitative structure-biodegradability relationship
      studies of the five NHCs showed that the anoxic degradation rates were correlated
      well with highest occupied molecular orbital. Additionally, the active sites of
      NHCs identified by calculation were confirmed by analysis of intermediates using
      gas chromatography and mass spectrometry.

PMID- 25968278
TI  - Adsorption of three pharmaceuticals on two magnetic ion-exchange resins.
AB  - The presence of pharmaceuticals in aquatic environments poses potential risks to
      the ecology and human health. This study investigated the removal of three widely
      detected and abundant pharmaceuticals, namely, ibuprofen (IBU), diclofenac (DC),
      and sulfadiazine (SDZ), by two magnetic ion-exchange resins. The adsorption
      kinetics of the three adsorbates onto both resins was relatively fast and
      followed pseudo-second-order kinetics. Despite the different pore structures of
      the two resins, similar adsorption patterns of DC and SDZ were observed, implying
      the existence of an ion-exchange mechanism. IBU demonstrated a combination of
      interactions during the adsorption process. These interactions were dependent on
      the specific surface area and functional groups of the resin. The adsorption
      isotherm fittings verified the differences in the behavior of the three
      pharmaceuticals on the two magnetic ion-exchange resins. The presence of Cl- and
      SO4(2-) suppressed the adsorption amount, but with different inhibition levels
      for different adsorbates. This work facilitates the understanding of the
      adsorption behavior and mechanism of pharmaceuticals on magnetic ion-exchange
      resins. The results will expand the application of magnetic ion-exchange resins
      to the removal of pharmaceuticals in waters.

PMID- 25968279
TI  - Rapid and simple spectrophotometric determination of persulfate in water by
      microwave assisted decolorization of Methylene Blue.
AB  - A rapid and simple method for determination of persulfate in aqueous solution was
      developed. The method is based on the rapid reaction of persulfate with Methylene
      Blue (MB) via domestic microwave activation, which can promote the activation of
      persulfate and decolorize MB quickly. The depletion of MB at 644 nm (the maximum
      absorption wavelength of MB) is in proportion to the increasing concentration of
      persulfate in aqueous solution. Linear calibration curve was obtained in the
      range 0-1.5 mmol/L, with a limit of detection of 0.0028 mmol/L. The reaction time
      is rapid (within 60 sec), which is much shorter than that used for conventional
      methods. Compared with existing analytical methods, it need not any additives,
      especially colorful Fe2+, and need not any pretreatment for samples, such as pH
      adjustment.

PMID- 25968280
TI  - Effect of water vapor on NH3-NO/NO2 SCR performance of fresh and aged MnOx-NbOx
      CeO2 catalysts.
AB  - A MnOx-NbOx-CeO2 catalyst for low temperature selective catalytic reduction (SCR)
      of NOx with NH3 was prepared by a sol-gel method, and characterized by NH3-NO/NO2
      SCR catalytic activity, NO/NH3 oxidation activity, NOx/NH3 TPD, XRD, BET, H2-TPR
      and in-situ Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS).
      The results indicate that the MnOx-NbOx-CeO2 catalyst shows excellent low
      temperature NH3-SCR activity in the temperature range of 150-300 degrees C. Water
      vapor inhibits the low temperature activity of the catalyst in standard SCR due
      to the inhibition of NOx adsorption. As the NO2 content increases in the feed,
      water vapor does not affect the activity in NO2 SCR. Meanwhile, water vapor
      significantly enhances the N2 selectivity of the fresh and the aged catalysts due
      to its inhibition of the decomposition of NH4NO3 into N2O. 

PMID- 25968281
TI  - [Motility disorders of the gastrointestinal tract].

PMID- 25968282
TI  - Which way to take? Infants select an efficient path to their goal.
AB  - In two experiments, we examined the development of the ability to select
      efficient means in order to attain a goal in 1.5- and 2-year-olds (N = 79) using
      a setup in which two paths led to a goal. One of the paths was shorter, and thus
      more efficient, than the other path. Experiment 1 showed a strong tendency in
      both age groups to choose the shorter path. In Experiment 2, the shorter path was
      initially blocked and became available only after infants repeatedly took the
      longer path. Children demonstrated increasing use of the more efficient path over
      time. The results of both experiments point to some abilities of efficient action
      selection in infants.

PMID- 25968283
TI  - Design of a Catalytic Active Site for Electrochemical CO2 Reduction with Mn(I)
      Tricarbonyl Species.
AB  - The design, synthesis, and assessment of a new manganese-centered catalyst for
      the electrochemical reduction of CO2 is described. The reported species, MnBr(6
      (2-hydroxyphenol)-2,2'-bipyridine)(CO)3, includes a ligand framework with a
      phenolic proton in close proximity to the CO2 binding site, which allows for
      facile proton-assisted C-O bond cleavage. As a result of this modification, seven
      times the electrocatalytic current enhancement is observed compared to MnBr(2,2'
      bipyridine)(CO)3. Moreover, reduction is possible at only 440 mV of
      overpotential. Theoretical computations suggest that the entropic contribution to
      the activation free energy is partially responsible for the increased catalytic
      activity. Experimental work, including voltammetry and product quantification
      from controlled potential electrolysis, suggests a key mechanistic role for the
      phenolic proton in the conversion of CO2 to CO. 

PMID- 25968284
TI  - Antibiotic use: room for improvement.

PMID- 25968285
TI  - Non-cystic fibrosis bronchiectasis: clinical presentation, diagnosis and
      treatment, illustrated by data from a Dutch Teaching Hospital.
AB  - This review article describes the epidemiology, clinical presentation, diagnostic
      workup and treatment options in adult non-cystic fibrosis (non-CF) bronchiectasis
      (widening of mainly small and medium-sized bronchi as seen on chest computed
      tomography (CT) scan). We illustrate evidence from the literature with our own
      data retrieved from chart review, involving 236 adult patients with recurrent
      lower respiratory tract infections and high-resolution CT-proven non-CF
      bronchiectasis, who visited the outpatient clinic for respiratory diseases of a
      large Dutch teaching hospital between 2000 and 2010. Non-CF bronchiectasis can be
      described as a final common pathway of a vicious cycle of excessive bronchial
      inflammation, bacterial colonisation and infection. Non-CF bronchiectasis may
      arise from several causes, headed by infection and immunodeficiency, and is
      clinically characterised by a chronic, productive cough and infectious
      exacerbations. Once non-CF bronchiectasis is diagnosed using high-resolution CT
      scanning, a protocol-driven work-up to identify the underlying cause is
      recommended. Non-medicinal treatment options are primarily directed at clearance
      of bronchial secretions, which can further be improved by inhalation of
      hyperosmolar agents. Antibiotic treatment of exacerbations is a cornerstone
      medicinal treatment in bronchiectasis management. Patients with frequent
      exacerbations can be considered for long-term low-dose macrolide treatment,
      supported by robust evidence. Inhaled antibiotics might be beneficial in selected
      patients colonised with Pseudomonas aeruginosa. Important developments in the
      last decade include the introduction of international guidelines and the proposal
      for a validated scoring system for disease severity. Bronchiectasis patients are
      encountered by physicians in diverse medical professions and the disease itself
      is still underdiagnosed. The authors aim to increase awareness of the condition
      and provide practical tools for diagnosis and treatment. 

PMID- 25968286
TI  - Seoul hantavirus in brown rats in the Netherlands: implications for physicians-
      Epidemiology, clinical aspects, treatment and diagnostics.
AB  - The recent discovery of Seoul hantavirus (SEOV) presence in wild rat populations
      in the Netherlands has direct implications for Dutch clinicians and hantavirus
      diagnostics. SEOV is amongst the Old World hantaviruses which cause haemorrhagic
      fever and renal syndrome (HFRS) in humans. HFRS is characterised by a classical
      triad of fever, acute kidney injury and haemorrhage, but can show different signs
      and symptoms in specific cases. SEOV is transmitted from infected rats to humans
      by inhalation of aerosolised excreta. When compared with the known circulating
      hantaviruses in the Netherlands, Puumala (PUUV) and Tula (TULV), SEOV causes a
      more severe form of HFRS. Data from cohort studies undertaken in China and
      Northern Europe show differences in signs and symptoms at onset of disease,
      (haemorrhagic) complications and mortality. Furthermore, routine diagnostics
      currently available for hantavirus diagnosis in the Netherlands are not optimised
      for SEOV detection. The clinical outcome of an SEOV and PUUV infection will
      greatly benefit from an early diagnosis which will reduce the costs of
      unnecessary tests and treatments as well. The discovery of SEOV circulation in
      the Netherlands follows recent findings of SEOV infections in both rodents and
      humans in England, Wales, France, Belgium and Sweden, indicating the emerging
      character of SEOV and a high importance of this hantavirus for Public Health in
      large areas of Europe. Here, we review the current knowledge on the clinical
      manifestation of SEOV versus PUUV infections in humans, the treatment of clinical
      cases and diagnostics. 

PMID- 25968287
TI  - Identifying targets for quality improvement in hospital antibiotic prescribing.
AB  - OBJECTIVES: To audit antibiotic use in a university hospital and to identify
      targets for quality improvement in a setting with low antibiotic use and
      resistance rates. METHODOLOGY: A point-prevalence survey (PPS), using a patient
      based audit tool for antibiotic use, was executed in the Radboud University
      Medical Centre in May 2013. On one index day, all patients on systemic
      antibiotics hospitalised > 24 hours were included. Data regarding antibiotic
      prescriptions were extracted from the medical records. Multiple logistic
      regression analysis was performed in order to predict whether a variable was
      associated with low guideline compliance or a low rate of consulting an
      infectious disease specialist. RESULTS: 428 hospitalised patients were included,
      of whom 40.9% received antibiotics. Overall, 75.7% of all prescriptions were
      compliant with the guidelines in place and for 87.8% the reason for prescription
      was documented. Amoxicillin/clavulanic acid (OR = 4.08, 95% CI 1.57-10.56), and
      respiratory tract infections (RTI) (OR = 6.17, 95% CI 2.55-14.94) were associated
      with low compliance with guidelines. An infectious disease physician or medical
      microbiologist was less often consulted for empirical therapy (OR 23.21, 95% CI
      6.37-84.51) or empirical therapy continued > 72 hours (OR 14.69, 95% CI 3.56
      60.56) compared with prescriptions that were based on culture results. In
      addition, fewer consultations were requested for RTI (OR 4.47, 95% CI 1.39
      14.35). CONCLUSION: A PPS is a good tool to identify targets for antibiotic
      stewardship in routine clinical practice. Several areas for improvement, such as
      a low compliance with guidelines for amoxicillin/clavulanic acid and RTI, and a
      low rate of consulting an infectious disease physician or medical microbiologist
      concerning antibiotic therapy in case of RTI and empirical therapy continued > 72
      hours were identified.

PMID- 25968289
TI  - Serum kisspeptin levels across different phases of the menstrual cycle and their
      correlation with serum oestradiol.
AB  - OBJECTIVE: A rise in oestrogen in the preovulatory phase produces a GnRH-induced
      luteinising hormone surge. Oestrogen receptors are not found on GnRH neurons but
      these are present on kisspeptin neurons. That led us to hypothesise that serum
      kisspeptin levels may vary during various phases of the menstrual cycle in
      relation to serum oestradiol. METHODS: Thirty female students, 18-25 years old,
      Saudi nationality, with a regular menstrual cycle, were recruited from various
      health colleges of the University of Dammam, Saudi Arabia. Three blood samples
      per volunteer were collected at three different times: the early follicular,
      preovulatory and luteal phase. Serum kisspeptin and oestradiol were measured
      using ELISA kits. Comparison between individual subjects during the various
      phases was done by one-way, repeated-measures ANOVA. To discover which specific
      means differed, Bonferroni post hoc test was applied. Pearsons correlation was
      used to find out the relationship. RESULTS: There was a statistically significant
      increase (p < 0.001) in serum kisspeptin levels from the early follicular to the
      preovulatory phase (264.11+/-28.42 vs. 472.46+/-17.82 nmol/l respectively), and
      from the preovulatory to the luteal phase (472.46+/-17.82 vs. 724.79+/-36.85
      nmol/l respectively). Oestradiol levels also increased significantly (p = 0.006)
      from the early follicular to the preovulatory phase (45.85+/-5.34 vs. 79.07+/
      7.45 pg/ml respectively), Pearsons correlation revealed a statistically
      insignificant correlation between kisspeptin and oestradiol in all three phases.
      CONCLUSION: Endogenous kisspeptin secretion seems to vary across the different
      phases of the menstrual cycle and is not related to serum oestradiol.

PMID- 25968288
TI  - Burden of highly resistant microorganisms in a Dutch intensive care unit.
AB  - BACKGROUND: The occurrence of highly resistant microorganisms (HRMOs) is a major
      threat to critical care patients, leading to worse outcomes, need for isolation
      measures, and demand for second-line or rescue antibiotics. The aim of this study
      was to quantify the burden of HRMOs in an intensive care unit (ICU) for adult
      patients in a university hospital in the Netherlands. We evaluated local
      distribution of different HRMO categories and proportion of ICU-imported versus
      ICU- acquired HRMOs. Outcome of HRMO-positive patients versuscontrols was
      compared. METHODS: In this prospective single-centre study, culture results of
      all ICU patients during a four-month period were recorded, as well as APACHE
      scores, ICU mortality and length of stay (LOS) in the ICU. RESULTS: 58 of 962
      (6.0%) patients were HRMO positive during ICU stay. The majority (60%) of those
      patients were HRMO positive on ICU admission. HRMO-positive patients had
      significantly higher APACHE scores, longer LOS and higher mortality compared with
      controls. CONCLUSIONS: Our study suggests that a large part of antibiotic
      resistance in the ICU is imported. This underscores the importance of a robust
      surveillance and infection control program throughout the hospital, and implies
      that better recognition of those at risk for HRMO carriage before ICU admission
      may be worthwhile. Only a small minority of patients with HRMO at admission did
      not have any known risk factors for HRMO.

PMID- 25968290
TI  - A 'shocking' finish to the Dam tot Damloop event.
AB  - A patient with status epilepticus after long-distance running is described. The
      patient, a young woman, was brought to our hospital with status epilepticus after
      completing in a running event, probably caused by an extremely low phosphate
      level of 0.30 mmol/l. Hypophosphataemia is a rare complication of running and can
      be caused by the use of phosphate in the glycogenolyticand glycolytic pathway.

PMID- 25968291
TI  - Successful treatment of fulminant postoperative bleeding due to acquired
      haemophilia.
AB  - Acquired haemophilia is a rare but life-threatening phenomenon in patients who
      have undergone surgical treatment. We describe a patient with a history of
      pancreatic cancer and a conventional pancreaticoduodenectomy, who underwent
      elective resection of an enterocutaneous fistula, complicated by fulminant
      haemorrhagic shock, caused by acquired haemophilia A. Eventually, the bleeding
      was controlled by a combination of aggressive haemostatic and immunosuppressive
      therapy. Prompt diagnosis of acquired haemophilia is crucial to allow early and
      appropriate haemostatic treatment and reduce the period of increased bleeding
      risk by eradicating the inhibitor with immunosuppressive therapy. 

PMID- 25968292
TI  - A patient with flank pain and haematuria after allogeneic stem cell
      transplantation.

PMID- 25968294
TI  - Thigh mass in a 22-year-old female.

PMID- 25968296
TI  - PEEP in ICU patients without ARDS in the Netherlands: not a closed case.

PMID- 25968297
TI  - Evaluation of a vancomycin dosing protocol for intensive care unit patients.
AB  - Vancomycin is a glycopeptide antibiotic that needs to be dosed to achieve target
      trough levels of 15-20 mg/l. Dosing can be challenging in ICU patients. To
      optimise therapy, in ICU-pharmacy collaboration, a dosing protocol was introduced
      on the ICU of the Medical Center Leeuwarden, the Netherlands. The effectiveness
      in obtaining timely adequate trough levels was evaluated. We retrospectively
      analysed data from 59 patients. Results show that pharmacy involvement and
      introduction of the dosing protocol resulted in early adequate trough levels (p =
      0.016). Introduction of the protocol alone resulted in non-significant early
      accurate trough levels. The protocol should be used with caution in patients with
      a possibly unreliable estimated glomerular filtration rate. Careful protocol
      introduction is important.

PMID- 25968298
TI  - Transcatheter Renal Sympathetic Denervation: Chasing a Chimera or a Matter of
      Technological Improvements?

PMID- 25968299
TI  - Histamine and Its Relation to Allergens in the Skin Prick Test.

PMID- 25968300
TI  - Progress and Prospects of Long Noncoding RNAs (lncRNAs) in Hepatocellular
      Carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most frequently occurring cancers
      with poor prognosis, and novel diagnostic or prognostic biomarkers and
      therapeutic targets for HCC are urgently required. With the advance of high
      resolution microarrays and massively parallel sequencing technology, lncRNAs are
      suggested to play critical roles in the tumorigenesis and development of human
      HCC. To date, dysregulation of many HCC-related lncRNAs such as HULC, HOTAIR,
      MALAT1, and H19 have been identified. From transcriptional "noise" to
      indispensable elements, lncRNAs may re-write the central dogma. Also, lncRNAs
      found in body fluids have demonstrated their utility as fluid-based noninvasive
      markers for clinical use and as therapeutic targets for HCC. Even though several
      lncRNAs have been characterized, the underlying mechanisms of their contribution
      to HCC remain unknown, and many important questions about lncRNAs need resolving.
      A better understanding of the molecular mechanism in HCC-related lncRNAs will
      provide a rationale for novel effective lncRNA-based targeted therapies. In this
      review, we highlight the emerging roles of lncRNAs in HCC, and discuss their
      potential clinical applications as biomarkers for the diagnosis, prognosis,
      monitoring and treatment of HCC.

PMID- 25968301
TI  - Resina Draconis as a topical treatment for pressure ulcers: A systematic review
      and meta-analysis.
AB  - In recent years, a number of studies have reported on Resina Draconis (RD) as a
      topical treatment for pressure ulcers. To evaluate these studies, we performed a
      systematic review and meta-analysis aimed to examine the efficacy of RD for
      pressure ulcers. We searched eight electronic databases to identify randomized
      controlled trials in which RD treatment was compared with other topical treatment
      of pressure ulcers from 1980 to 2014. Selection of studies, study appraisal, data
      extraction and analysis were undertaken using standard methods. Fourteen
      randomized controlled trials were included involving 618 patients. The results of
      the meta-analysis showed that, RD treatment was significantly associated with a
      higher healing rate for pressure ulcers (risk ratio 2.07, 95% confidence
      intervals 1.73-2.48, p < 0.001). The results of descriptive analysis showed that,
      compared with the control group, RD treatment shortened healing time. As for
      safety, adverse reactions had not been reported. These results suggest that RD
      can improve the healing rate for pressure ulcers and shorten the healing time,
      compared with other topical treatments. However, due to limited quality and
      quantity of the included studies, this conclusion needs to be proved by more high
      quality studies. 

PMID- 25968302
TI  - Applicability of BALAD score in prognostication of hepatitis B-related
      hepatocellular carcinoma.
AB  - BACKGROUND AND AIMS: The BALAD score is developed to provide an objective
      determination of prognosis for hepatocellular carcinoma (HCC) by incorporating
      five serum markers, namely albumin, bilirubin, alpha-fetoprotein (AFP),
      agglutinin-reactive alpha-fetoprotein (AFP-L3), and des-gamma-carboxy
      prothrombin. We aim to study the applicability of BALAD score and prognostication
      of the three tumor markers in hepatitis B virus-related HCC. METHODS: Patients
      with newly diagnosed HCC were prospectively enrolled. All of the baseline
      characteristics and serum albumin and bilirubin level were documented at
      baseline. The levels of the three tumor markers (AFP, AFP-L3, and des-gamma
      carboxy prothrombin) were determined in archival serum samples. Patients were
      followed up for survivals according to local practice. The prognostic
      performances of the three markers and BALAD score were studied in association
      with overall survival (OS). RESULTS: A total of 198 patients with hepatitis B
      related HCC were recruited. AFP and AFP-L3 levels were independent prognostic
      factors. The number of elevated tumor markers was also predictive of worse OS.
      BALAD score could stratify the cohort into different patient groups with distinct
      median OS. The median OS of BALAD score of 0, 1, 2, 3, and 4 was not reached,
      26.6, 8.3, 2.6, and 1.9 months, respectively (P < 0.0001). BALAD score could
      further stratify outcomes in each Barcelona Clinic Liver Cancer (BCLC) subgroup.
      In particular, BALAD score of 3-4 had median OS of 2.6 months only in BCLC stage
      C patients. CONCLUSION: BALAD score is applicable in the population of hepatitis
      B virus-related HCC. The combined use of BALAD score and BCLC staging system
      could help identify more suitable candidates for clinical trial.

PMID- 25968303
TI  - What is the effect of a formalised trauma tertiary survey procedure on missed
      injury rates in multi-trauma patients? Study protocol for a randomised controlled
      trial.
AB  - BACKGROUND: Missed injury is commonly used as a quality indicator in trauma care.
      The trauma tertiary survey (TTS) has been proposed to reduce missed injuries.
      However a systematic review assessing the effect of the TTS on missed injury
      rates in trauma patients found only observational studies, only suggesting a
      possible increase in early detection and reduction in missed injuries, with
      significant potential biases. Therefore, more robust methods are necessary to
      test whether implementation of a formal TTS will increase early in-hospital
      injury detection, decrease delayed diagnosis and decrease missed injuries after
      hospital discharge. METHODS/DESIGN: We propose a cluster-randomised, controlled
      trial to evaluate trauma care enhanced with a formalised TTS procedure.
      Currently, 20 to 25% of trauma patients routinely have a TTS performed. We expect
      this to increase to at least 75%. The design is for 6,380 multi-trauma patients
      in approximately 16 hospitals recruited over 24 months. In the first 12 months,
      patients will be randomised (by hospital) and allocated 1:1 to receive either the
      intervention (Group 1) or usual care (Group 2). The recruitment for the second 12
      months will entail Group 1 hospitals continuing the TTS, and the Group 2
      hospitals beginning it to enable estimates of the persistence of the
      intervention. The intervention is complex: implementation of formal TTS form,
      small group education, and executive directive to mandate both. Outcome data will
      be prospectively collected from (electronic) medical records and patient
      (telephone follow-up) questionnaires. Missed injuries will be adjudicated by a
      blinded expert panel. The primary outcome is missed injuries after hospital
      discharge; secondary outcomes are maintenance of the intervention effect, in
      hospital missed injuries, tertiary survey performance rate, hospital and ICU bed
      days, interventions required for missed injuries, advanced diagnostic imaging
      requirements, readmissions to hospital, days of work and quality of life (EQ-5D-5
      L) and mortality. DISCUSSION: The findings of this study may alter the delivery
      of international trauma care. If formal TTS is (cost-) effective this
      intervention should be implemented widely. If not, where already partly
      implemented, it should be abandoned. Study findings will be disseminated widely
      to relevant clinicians and health funders. TRIAL REGISTRATION: ANZCTR:
      ACTRN12613001218785, prospectively registered, 5 November 2013.

PMID- 25968304
TI  - Acute myocardial infarction and cardiogenic shock: pharmacologic and mechanical
      hemodynamic support pathways.
AB  - Cardiogenic shock (CS) is still the predominant cause of in-hospital death in
      patients with acute myocardial infarction, although mortality has been reduced in
      recent years. Early percutaneous coronary intervention and coronary artery bypass
      grafting are causal therapies implemented in CS, supported by catecholamines,
      fluids, intra-aortic balloon pumping, and also active percutaneous assist
      devices. There is only limited evidence from randomized studies of any of these
      treatments in CS, except for early revascularization and the relative
      ineffectiveness of intra-aortic balloon pumping. This review will present
      treatment pathways of CS complicating acute myocardial infarction, with a major
      focus on revascularization, intensive care unit treatment, and mechanical support
      devices. 

PMID- 25968305
TI  - Carbohydrate antigen 125 levels and clinical outcomes after off-pump coronary
      artery bypass grafting.
AB  - OBJECTIVES: The present study aimed to evaluate the prognostic value of
      preoperative carbohydrate antigen 125 (CA125) levels for clinical outcomes after
      off-pump coronary artery bypass grafting (OPCAB). METHODS: A total of 314
      consecutive patients who underwent OPCAB were enrolled in this study and divided
      into three groups corresponding to baseline CA125 level tertiles. Clinical
      outcomes of these patients were followed up after 1 year. The primary endpoint
      was the incidence of combined major adverse cardiac events (MACE). RESULTS: Event
      free survival was significantly associated with the CA125 tertile (log-rank
      P=0.021); specifically, hazard ratios (HRs) increased progressively from CA125
      tertile 1 to tertile 3 [vs. tertile 1: tertile 2 h=1.8; 95% confidence interval
      (CI): 1.1-2.8, P=0.040; tertile 3 h=2.9; 95% CI: 1.1-8.1, P=0.018]. In the first
      multivariate Cox regression analytical model (all variables except EuroSCORE),
      CA125 was an independent predictor of MACE (HR=1.1, 95% CI: 1.0-2.4, P=0.016). In
      a second model (CA125 levels and EuroSCORE only), CA125 remained an independent
      predictor of MACE (HR=1.1, 95% CI: 1.0-1.3, P=0.036). CONCLUSION: An increased
      preoperative CA125 level is an independent predictor of worse clinical outcomes
      after OPCAB during a 1-year follow-up.

PMID- 25968307
TI  - An interview with Juergen Knoblich.
AB  - Juergen Knoblich is a senior scientist and deputy scientific director of the
      Institute of Molecular Biotechnology of the Austrian Academy of Sciences in
      Vienna. We met Juergen at the 56(th) Annual Drosophila Research Conference, where
      we asked him about his work in this model system and, more recently, on human
      cerebral organoids, and about his thoughts on recent technological developments
      and the funding situation. 

PMID- 25968306
TI  - Low serum testosterone level was associated with extensive coronary artery
      calcification in elderly male patients with stable coronary artery disease.
AB  - BACKGROUND: Coronary artery calcification (CAC) is a pandemic condition in
      elderly patients with coronary artery disease (CAD) and associated with a worse
      prognosis. Although available data have shown an association between testosterone
      levels in men and CAD, the association between testosterone and CAC in elderly
      male patients with CAD remains unknown. METHODS: A total of 211 consecutive male
      patients (age >= 65 years) who underwent first multidetector computed tomography
      and following angiography were enrolled from our institution between March 2009
      and September 2014. CAD was angiographically documented as significant stenoses
      (reduction >= 50% of the lumen diameter) on any major coronary vessel. The
      standard Agatston calcium score was calculated. The relationship of serum
      testosterone level with the CAC score measured by multidetector computed
      tomography in elderly male patients with stable CAD was evaluated. For data
      analyses, the CAC score was divided into four categories: <= 10, 11-99, 100-399,
      and >= 400, corresponding to minimal, moderate, increased, and extensive
      calcification. RESULTS: Patients with higher CAC scores had significantly lower
      testosterone levels than patients with lower CAC scores (P = 0.048). In logistic
      regression analysis, testosterone level remained an independent predictor of
      extensive CAC (odds ratio 0.997, 95% confidence interval 0.994-0.999, P = 0.043).
      CONCLUSION: Our findings indicate an inverse association between testosterone
      level and the susceptibility to extensive CAC in elderly men with stable CAD.

PMID- 25968308
TI  - Hematopoietic development at high altitude: blood stem cells put to the test.
AB  - In February 2015, over 200 scientists gathered for the Keystone Hematopoiesis
      meeting, which was held at the scenic Keystone Resort in Keystone, Colorado, USA.
      The meeting organizers, Patricia Ernst, Hanna Mikkola and Timm Schroeder, put
      together an exciting program, during which field leaders and new investigators
      presented discoveries that spanned developmental and adult hematopoiesis within
      both physiologic and pathologic contexts. Collectively, the program highlighted
      the increasing pace of new discoveries and the substantial progress made in the
      hematopoiesis field since the last Keystone meeting two years ago. In this
      Meeting Review, we highlight the main concepts discussed at the conference, with
      an emphasis on topics relevant to developmental biology. 

PMID- 25968309
TI  - Building the backbone: the development and evolution of vertebral patterning.
AB  - The segmented vertebral column comprises a repeat series of vertebrae, each
      consisting of two key components: the vertebral body (or centrum) and the
      vertebral arches. Despite being a defining feature of the vertebrates, much
      remains to be understood about vertebral development and evolution. Particular
      controversy surrounds whether vertebral component structures are homologous
      across vertebrates, how somite and vertebral patterning are connected, and the
      developmental origin of vertebral bone-mineralizing cells. Here, we assemble
      evidence from ichthyologists, palaeontologists and developmental biologists to
      consider these issues. Vertebral arch elements were present in early stem
      vertebrates, whereas centra arose later. We argue that centra are homologous
      among jawed vertebrates, and review evidence in teleosts that the notochord plays
      an instructive role in segmental patterning, alongside the somites, and
      contributes to mineralization. By clarifying the evolutionary relationship
      between centra and arches, and their varying modes of skeletal mineralization, we
      can better appreciate the detailed mechanisms that regulate and diversify
      vertebral patterning. 

PMID- 25968310
TI  - CSR-1 and P granules suppress sperm-specific transcription in the C. elegans
      germline.
AB  - Germ granules (P granules) in C. elegans are required for fertility and function
      to maintain germ cell identity and pluripotency. Sterility in the absence of P
      granules is often accompanied by the misexpression of soma-specific proteins and
      the initiation of somatic differentiation in germ cells. To investigate whether
      this is caused by the accumulation of somatic transcripts, we performed mRNA-seq
      on dissected germlines with and without P granules. Strikingly, we found that
      somatic transcripts do not increase in the young adult germline when P granules
      are impaired. Instead, we found that impairing P granules causes sperm-specific
      mRNAs to become highly overexpressed. This includes the accumulation of major
      sperm protein (MSP) transcripts in germ cells, a phenotype that is suppressed by
      feminization of the germline. A core component of P granules, the endo-siRNA
      binding Argonaute protein CSR-1, has recently been ascribed with the ability to
      license transcripts for germline expression. However, impairing CSR-1 has very
      little effect on the accumulation of its mRNA targets. Instead, we found that CSR
      1 functions with P granules to prevent MSP and sperm-specific mRNAs from being
      transcribed in the hermaphrodite germline. These findings suggest that P granules
      protect germline integrity through two different mechanisms, by (1) preventing
      the inappropriate expression of somatic proteins at the level of translational
      regulation, and by (2) functioning with CSR-1 to limit the domain of sperm
      specific expression at the level of transcription. 

PMID- 25968311
TI  - The regulated elimination of transit-amplifying cells preserves tissue
      homeostasis during protein starvation in Drosophila testis.
AB  - How tissues adapt to varying nutrient conditions is of fundamental importance for
      robust tissue homeostasis throughout the life of an organism, but the underlying
      mechanisms are poorly understood. Here, we show that Drosophila testis responds
      to protein starvation by eliminating transit-amplifying spermatogonia (SG) while
      maintaining a reduced pool of actively proliferating germline stem cells (GSCs).
      During protein starvation, SG die in a manner that is mediated by the apoptosis
      of somatic cyst cells (CCs) that encapsulate SG and regulate their development.
      Strikingly, GSCs cannot be maintained during protein starvation when CC-mediated
      SG death is inhibited, leading to an irreversible collapse of tissue homeostasis.
      We propose that the regulated elimination of transit-amplifying cells is
      essential to preserve stem cell function and tissue homeostasis during protein
      starvation. 

PMID- 25968312
TI  - Glypican4 promotes cardiac specification and differentiation by attenuating
      canonical Wnt and Bmp signaling.
AB  - Glypicans are heparan sulphate proteoglycans (HSPGs) attached to the cell
      membrane by a glycosylphosphatidylinositol (GPI) anchor, and interact with
      various extracellular growth factors and receptors. The Drosophila division
      abnormal delayed (dally) was the first glypican loss-of-function mutant described
      that displays disrupted cell divisions in the eye and morphological defects in
      the wing. In human, as in most vertebrates, six glypican-encoding genes have been
      identified (GPC1-6), and mutations in several glypican genes cause multiple
      malformations including congenital heart defects. To understand better the role
      of glypicans during heart development, we studied the zebrafish knypek mutant,
      which is deficient for Gpc4. Our results demonstrate that knypek/gpc4 mutant
      embryos display severe cardiac defects, most apparent by a strong reduction in
      cardiomyocyte numbers. Cell-tracing experiments, using photoconvertable
      fluorescent proteins and genetic labeling, demonstrate that Gpc4 'Knypek' is
      required for specification of cardiac progenitor cells and their differentiation
      into cardiomyocytes. Mechanistically, we show that Bmp signaling is enhanced in
      the anterior lateral plate mesoderm of knypek/gpc4 mutants and that genetic
      inhibition of Bmp signaling rescues the cardiomyocyte differentiation defect
      observed in knypek/gpc4 embryos. In addition, canonical Wnt signaling is
      upregulated in knypek/gpc4 embryos, and inhibiting canonical Wnt signaling in
      knypek/gpc4 embryos by overexpression of the Wnt inhibitor Dkk1 restores normal
      cardiomyocyte numbers. Therefore, we conclude that Gpc4 is required to attenuate
      both canonical Wnt and Bmp signaling in the anterior lateral plate mesoderm to
      allow cardiac progenitor cells to specify and differentiate into cardiomyocytes.
      This provides a possible explanation for how congenital heart defects arise in
      glypican-deficient patients. 

PMID- 25968313
TI  - Girdin-mediated interactions between cadherin and the actin cytoskeleton are
      required for epithelial morphogenesis in Drosophila.
AB  - E-cadherin-mediated cell-cell adhesion is fundamental for epithelial tissue
      morphogenesis, physiology and repair. E-cadherin is a core transmembrane
      constituent of the zonula adherens (ZA), a belt-like adherens junction located at
      the apicolateral border in epithelial cells. The anchorage of ZA components to
      cortical actin filaments strengthens cell-cell cohesion and allows for junction
      contractility, which shapes epithelial tissues during development. Here, we
      report that the cytoskeletal adaptor protein Girdin physically and functionally
      interacts with components of the cadherin-catenin complex during Drosophila
      embryogenesis. Fly Girdin is broadly expressed throughout embryonic development
      and enriched at the ZA in epithelial tissues. Girdin associates with the
      cytoskeleton and co-precipitates with the cadherin-catenin complex protein alpha
      Catenin (alpha-Cat). Girdin mutations strongly enhance adhesion defects
      associated with reduced DE-cadherin (DE-Cad) expression. Moreover, the fraction
      of DE-Cad molecules associated with the cytoskeleton decreases in the absence of
      Girdin, thereby identifying Girdin as a positive regulator of adherens junction
      function. Girdin mutant embryos display isolated epithelial cell cysts and
      rupture of the ventral midline, consistent with defects in cell-cell cohesion. In
      addition, loss of Girdin impairs the collective migration of epithelial cells,
      resulting in dorsal closure defects. We propose that Girdin stabilizes epithelial
      cell adhesion and promotes morphogenesis by regulating the linkage of the
      cadherin-catenin complex to the cytoskeleton. 

PMID- 25968315
TI  - A cellular process that includes asymmetric cytokinesis remodels the dorsal
      tracheal branches in Drosophila larvae.
AB  - Tubular networks are central to the structure and function of many organs, such
      as the vertebrate lungs or the Drosophila tracheal system. Their component
      epithelial cells are able to proliferate and to undergo complex morphogenetic
      movements, while maintaining their barrier function. Little is known about the
      details of the mitotic process in tubular epithelia. Our study presents a
      comprehensive model of cellular remodeling and proliferation in the dorsal
      branches of third-instar Drosophila larvae. Through a combination of
      immunostaining and novel live imaging techniques, we identify the key steps in
      the transition from a unicellular to a multicellular tube. Junctional remodeling
      precedes mitosis and, as the cells divide, new junctions are formed through
      several variations of what we refer to as 'asymmetric cytokinesis'. Depending on
      the spacing of cells along the dorsal branch, mitosis can occur either before or
      after the transition to a multicellular tube. In both instances, cell separation
      is accomplished through asymmetric cytokinesis, a process that is initiated by
      the ingression of the cytokinetic ring. Unequal cell compartments are a possible
      but rare outcome of completing mitosis through this mechanism. We also found that
      the Dpp signaling pathway is required but not sufficient for cell division in the
      dorsal branches. 

PMID- 25968314
TI  - Dynamics of the slowing segmentation clock reveal alternating two-segment
      periodicity.
AB  - The formation of reiterated somites along the vertebrate body axis is controlled
      by the segmentation clock, a molecular oscillator expressed within presomitic
      mesoderm (PSM) cells. Although PSM cells oscillate autonomously, they coordinate
      with neighboring cells to generate a sweeping wave of cyclic gene expression
      through the PSM that has a periodicity equal to that of somite formation. The
      velocity of each wave slows as it moves anteriorly through the PSM, although the
      dynamics of clock slowing have not been well characterized. Here, we investigate
      segmentation clock dynamics in the anterior PSM in developing zebrafish embryos
      using an in vivo clock reporter, her1:her1-venus. The her1:her1-venus reporter
      has single-cell resolution, allowing us to follow segmentation clock oscillations
      in individual cells in real-time. By retrospectively tracking oscillations of
      future somite boundary cells, we find that clock reporter signal increases in
      anterior PSM cells and that the periodicity of reporter oscillations slows to
      about ~1.5 times the periodicity in posterior PSM cells. This gradual slowing of
      the clock in the anterior PSM creates peaks of clock expression that are
      separated at a two-segment periodicity both spatially and temporally, a
      phenomenon we observe in single cells and in tissue-wide analyses. These results
      differ from previous predictions that clock oscillations stop or are stabilized
      in the anterior PSM. Instead, PSM cells oscillate until they incorporate into
      somites. Our findings suggest that the segmentation clock may signal somite
      formation using a phase gradient with a two-somite periodicity. 

PMID- 25968316
TI  - Neural retina identity is specified by lens-derived BMP signals.
AB  - The eye has served as a classical model to study cell specification and tissue
      induction for over a century. Nevertheless, the molecular mechanisms that
      regulate the induction and maintenance of eye-field cells, and the specification
      of neural retina cells are poorly understood. Moreover, within the developing
      anterior forebrain, how prospective eye and telencephalic cells are
      differentially specified is not well defined. In the present study, we have
      analyzed these issues by manipulating signaling pathways in intact chick embryo
      and explant assays. Our results provide evidence that at blastula stages, BMP
      signals inhibit the acquisition of eye-field character, but from neural
      tube/optic vesicle stages, BMP signals from the lens are crucial for the
      maintenance of eye-field character, inhibition of dorsal telencephalic cell
      identity and specification of neural retina cells. Subsequently, our results
      provide evidence that a Rax2-positive eye-field state is not sufficient for the
      progress to a neural retina identity, but requires BMP signals. In addition, our
      results argue against any essential role of Wnt or FGF signals during the
      specification of neural retina cells, but provide evidence that Wnt signals
      together with BMP activity are sufficient to induce cells of retinal pigment
      epithelial character. We conclude that BMP activity emanating from the lens
      ectoderm maintains eye-field identity, inhibits telencephalic character and
      induces neural retina cells. Our findings link the requirement of the lens
      ectoderm for neural retina specification with the molecular mechanism by which
      cells in the forebrain become specified as neural retina by BMP activity. 

PMID- 25968317
TI  - Local homeoprotein diffusion can stabilize boundaries generated by graded
      positional cues.
AB  - Boundary formation in the developing neuroepithelium decides on the position and
      size of compartments in the adult nervous system. In this study, we start from
      the French Flag model proposed by Lewis Wolpert, in which boundaries are formed
      through the combination of morphogen diffusion and of thresholds in cell
      responses. In contemporary terms, a response is characterized by the expression
      of cell-autonomous transcription factors, very often of the homeoprotein family.
      Theoretical studies suggest that this sole mechanism results in the formation of
      boundaries of imprecise shapes and positions. Alan Turing, on the other hand,
      proposed a model whereby two morphogens that exhibit self-activation and
      reciprocal inhibition, and are uniformly distributed and diffuse at different
      rates lead to the formation of territories of unpredictable shapes and positions
      but with sharp boundaries (the 'leopard spots'). Here, we have combined the two
      models and compared the stability of boundaries when the hypothesis of local
      homeoprotein intercellular diffusion is, or is not, introduced in the equations.
      We find that the addition of homeoprotein local diffusion leads to a dramatic
      stabilization of the positioning of the boundary, even when other parameters are
      significantly modified. This novel Turing/Wolpert combined model has thus
      important theoretical consequences for our understanding of the role of the
      intercellular diffusion of homeoproteins in the developmental robustness of and
      the changes that take place in the course of evolution. 

PMID- 25968318
TI  - Live imaging of endogenous protein dynamics in zebrafish using chromobodies.
AB  - Chromobodies are intracellular nanoprobes that combine the specificity of
      antibodies with the convenience of live fluorescence imaging in a flexible, DNA
      encoded reagent. Here, we present the first application of this technique to an
      intact living vertebrate organism. We generated zebrafish lines expressing
      chromobodies that trace the major cytoskeletal component actin and the cell cycle
      marker PCNA with spatial and temporal specificity. Using these chromobodies, we
      captured full localization dynamics of the endogenous antigens in different cell
      types and at different stages of development. For the first time, the chromobody
      technology enables live imaging of endogenous subcellular structures in an
      animal, with the remarkable advantage of avoiding target protein overexpression
      or tagging. In combination with improved chromobody selection systems, we
      anticipate a rapid adaptation of this technique to new intracellular antigens and
      model organisms, allowing the faithful description of cellular and molecular
      processes in their dynamic state. 

PMID- 25968319
TI  - Enhanced selective gene delivery to neural stem cells in vivo by an adeno
      associated viral variant.
AB  - Neural stem cells (NSCs) are defined by their ability to self-renew and to
      differentiate into mature neuronal and glial cell types. NSCs are the subject of
      intense investigation, owing to their crucial roles in neural development and
      adult brain function and because they present potential targets for gene and cell
      replacement therapies following injury or disease. Approaches to specifically
      genetically perturb or modulate NSC function would be valuable for either
      motivation. Unfortunately, most gene delivery vectors are incapable of efficient
      or specific gene delivery to NSCs in vivo. Vectors based on adeno-associated
      virus (AAV) present a number of advantages and have proven increasingly
      successful in clinical trials. However, natural AAV variants are inefficient in
      transducing NSCs. We previously engineered a novel AAV variant (AAV r3.45)
      capable of efficient transduction of adult NSCs in vitro. Here, to build upon the
      initial promise of this variant, we investigated its in vitro and in vivo
      infectivity. AAV r3.45 was more selective for NSCs than mature neurons in a human
      embryonic stem cell-derived culture containing a mixture of cell types, including
      NSCs and neurons. It was capable of more efficient and selective transduction of
      rat and mouse NSCs in vivo than natural AAV serotypes following intracranial
      vector administration. Delivery of constitutively active beta-catenin yielded
      insights into mechanisms by which this key regulator modulates NSC function,
      indicating that this engineered AAV variant can be harnessed for preferential
      modulation of adult NSCs in the hippocampus. The capacity to rapidly genetically
      modify these cells might greatly accelerate in vivo investigations of adult
      neurogenesis. 

PMID- 25968321
TI  - Repeated Measurement of Crown-Rump Length at 9 and 11-13 Weeks' Gestation:
      Association with Adverse Pregnancy Outcome.
AB  - AIMS: To clarify whether ultrasonographic measurements of crown-rump length (CRL)
      at 11-13 weeks - based on the number of gestational days determined using the CRL
      at 9 weeks - can predict fetal prognosis. METHODS: A prospective cohort study was
      conducted to evaluate the association between fetal growth in the first trimester
      and fetal prognosis. Fetal growth in the first trimester was evaluated measuring
      CRLs at 11-13 weeks determined using the CRL at 9 weeks. The subjects were
      divided into short CRL (s-CRL) and normal CRL (n-CRL). The prognoses were
      compared between the two groups. RESULTS: A total of 126 patients in the s-CRL
      group and 1,130 patients in the n-CRL group were enrolled. Abortion occurred in
      7.1% of s-CRL and 0.9% of n-CRL subjects (p < 0.001). Among the patients with
      chromosomal abnormalities, the incidence of trisomy 18 was significantly greater
      in s-CRL (4.8 vs. 0.1%, p < 0.001). Without abortion, placental weight, frequency
      of small for gestational age (SGA) and birth weight in s-CRL were significantly
      higher than those in the n-CRL group (12.8 vs. 3.6%, p < 0.001). CONCLUSIONS:
      Measuring CRL at 9 weeks is useful for determining gestational days prior to
      measuring CRL at 11-13 weeks. After reconfirming the gestational age at 9 weeks,
      measuring CRL at 11-13 weeks is useful for predicting the incidence of trisomy 18
      as well as SGA later in pregnancy.

PMID- 25968320
TI  - An illustrated anatomical ontology of the developing mouse lower urogenital
      tract.
AB  - Malformation of the urogenital tract represents a considerable paediatric burden,
      with many defects affecting the lower urinary tract (LUT), genital tubercle and
      associated structures. Understanding the molecular basis of such defects
      frequently draws on murine models. However, human anatomical terms do not always
      superimpose on the mouse, and the lack of accurate and standardised nomenclature
      is hampering the utility of such animal models. We previously developed an
      anatomical ontology for the murine urogenital system. Here, we present a
      comprehensive update of this ontology pertaining to mouse LUT, genital tubercle
      and associated reproductive structures (E10.5 to adult). Ontology changes were
      based on recently published insights into the cellular and gross anatomy of these
      structures, and on new analyses of epithelial cell types present in the pelvic
      urethra and regions of the bladder. Ontology changes include new structures,
      tissue layers and cell types within the LUT, external genitalia and lower
      reproductive structures. Representative illustrations, detailed text descriptions
      and molecular markers that selectively label muscle, nerves/ganglia and epithelia
      of the lower urogenital system are also presented. The revised ontology will be
      an important tool for researchers studying urogenital development/malformation in
      mouse models and will improve our capacity to appropriately interpret these with
      respect to the human situation. 

PMID- 25968322
TI  - Metagenomics reveals the high polycyclic aromatic hydrocarbon-degradation
      potential of abundant uncultured bacteria from chronically polluted subantarctic
      and temperate coastal marine environments.
AB  - AIMS: To investigate the potential to degrade polycyclic aromatic hydrocarbons
      (PAHs) of yet-to-be-cultured bacterial populations from chronically polluted
      intertidal sediments. METHODS AND RESULTS: A gene variant encoding the alpha
      subunit of the catalytic component of an aromatic-ring-hydroxylating oxygenase
      (RHO) was abundant in intertidal sediments from chronically polluted subantarctic
      and temperate coastal environments, and its abundance increased after PAH
      amendment. Conversely, this marker gene was not detected in sediments from a
      nonimpacted site, even after a short-term PAH exposure. A metagenomic fragment
      carrying this gene variant was identified in a fosmid library of subantarctic
      sediments. This fragment contained five pairs of alpha and beta subunit genes and
      a lone alpha subunit gene of oxygenases, classified as belonging to three
      different RHO functional classes. In silico structural analysis suggested that
      two of these oxygenases contain large substrate-binding pockets, capable of
      accepting high molecular weight PAHs. CONCLUSIONS: The identified uncultured
      micro-organism presents the potential to degrade aromatic hydrocarbons with
      various chemical structures, and could represent an important member of the PAH
      degrading community in these polluted coastal environments. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This work provides valuable information for the design of
      environmental molecular diagnostic tools and for the biotechnological application
      of RHO enzymes.

PMID- 25968323
TI  - PhyTB: Phylogenetic tree visualisation and sample positioning for M.
      tuberculosis.
AB  - BACKGROUND: Phylogenetic-based classification of M. tuberculosis and other
      bacterial genomes is a core analysis for studying evolutionary hypotheses,
      disease outbreaks and transmission events. Whole genome sequencing is providing
      new insights into the genomic variation underlying intra- and inter-strain
      diversity, thereby assisting with the classification and molecular barcoding of
      the bacteria. One roadblock to strain investigation is the lack of user
      interactive solutions to interrogate and visualise variation within a
      phylogenetic tree setting. RESULTS: We have developed a web-based tool called
      PhyTB ( http://pathogenseq.lshtm.ac.uk/phytblive/index.php ) to assist
      phylogenetic tree visualisation and identification of M. tuberculosis clade
      informative polymorphism. Variant Call Format files can be uploaded to determine
      a sample position within the tree. A map view summarises the geographical
      distribution of alleles and strain-types. The utility of the PhyTB is
      demonstrated on sequence data from 1,601 M. tuberculosis isolates. CONCLUSION:
      PhyTB contextualises M. tuberculosis genomic variation within epidemiological,
      geographical and phylogenic settings. Further tool utility is possible by
      incorporating large variants and phenotypic data (e.g. drug-resistance profiles),
      and an assessment of genotype-phenotype associations. Source code is available to
      develop similar websites for other organisms (
      http://sourceforge.net/projects/phylotrack ).

PMID- 25968324
TI  - Appropriate use of antimicrobial prophylaxis: an observational study in 21
      surgical wards.
AB  - BACKGROUND: Surveillance of Surgical Site Infections (SSI) in 2010 found 39 %
      compliance with hospital guidelines in Piedmont (Italy). The aim of the study was
      to estimate the appropriate use of antimicrobial prophylaxis and compliance with
      hospitals guidelines in surgical wards. METHODS: This survey study took place in
      21 surgery wards of 4 public hospitals. Forms were completed by public health
      resident doctors together with a medical ward referent and infection control
      nurses. 15 consecutive surgical procedures were randomly chosen from each ward. A
      total of 320 cases were analyzed. The study period was from July 2012 to January
      2013. Data were collected using a survey form. A final score variable from 0 to 4
      was given to each case. The results were compared with hospital and international
      guidelines. Data were analyzed using Epi-Info software. RESULTS: Of the 320 cases
      collected, 63 were excluded; of the remaining 257 cases, 56.4 % of the procedures
      were appropriate (score 4), 15.2 % were acceptable and 28.4 % were not
      acceptable. The study found an unjustified continuation of antimicrobial
      prophylaxis in 17.1 % of the 257 cases, an unjustified re-start of antimicrobial
      therapy in 9.7 % and a re-dosing omission in 7.8 %. CONCLUSIONS: The study
      demonstrated critical problems in antimicrobial prophylaxis management in
      surgical wards due to a lack of compliance between hospitals and national
      guidelines, a shortage of specific and updated recommendations for some surgical
      interventions and incorrect local specific procedures. Coordination between local
      and national recommendations, strengthening of evidence based decisions and
      continuous sharing of policy updates are needed.

PMID- 25968325
TI  - Apathy, ventriculomegaly and neurocognitive improvement following shunt surgery
      in normal pressure hydrocephalus.
AB  - INTRODUCTION: Apathy - impaired motivation and goal-directed behaviour - is a
      common yet often overlooked symptom in normal pressure hydrocephalus (NPH).
      Caudate atrophy often yields apathetic symptoms; however, this structural and
      functional relationship has not yet been explored in NPH. Additionally, little is
      known about the relationship between apathy and post-shunt cognitive recovery.
      METHODS: This audit investigated whether apathetic symptoms improve following
      shunt surgery in NPH, and whether this relates to cognitive response. In
      addition, we assessed the relationship between ventriculomegaly and apathy using
      the bicaudate ratio. Twenty-two patients with NPH completed the Mini-Mental State
      Examination (MMSE), the Apathy Evaluation Scale (AES) and the Geriatric
      Depression Scale (GDS) before and 3-9 months after shunt surgery. Pre-operative
      ventriculomegaly was correlated with pre-operative AES and GDS scores. Difference
      scores (post-shunt minus baseline values) for AES and GDS were correlated with
      cognitive outcome. RESULTS: Greater pre-operative ventriculomegaly was associated
      with increased level of apathy and depression. A reduction in apathetic symptoms
      following shunt surgery was associated with improved performance on the MMSE.
      CONCLUSIONS: Apathy may be indicative of a greater degree of subcortical atrophy
      in NPH and may relate to functional outcome.

PMID- 25968326
TI  - Mononostril endoscopic transsphenoidal approach to sellar and peri-sellar
      lesions: Personal experience and literature review.
AB  - OBJECTIVE: The endonasal endoscopic approach to skull base is still under
      investigation. The main goal is the minimal invasive approach to pathologies with
      a better rate of resection without retraction of the brain tissue. Here, the
      authors report their technique of transnasal endoscopic neurosurgery using a
      mononostril approach and its development. METHODS: The supplementary video
      demonstrates the different steps of the mononostril approach and resection of a
      pituitary adenoma. All video-recorded procedures that were carried out between
      2000 and 2013 using this technique were analysed. The patients were followed
      prospectively. RESULTS: Visualization and handling were good in 246/251 (98%). In
      three cases, we had to switch to microscopy because of severe bleeding of the
      cavernous sinus. On follow-up, magnetic resonance imaging revealed radical tumour
      resection in 92% of all cases when intended. There was no mortality, and the low
      complication rate was remarkable. CONCLUSION: Our mononostril approach of
      transnasal transsphenoidal surgery shows better results compared with previously
      published reports in regards to radicality, low cerebrospinal fluid leaks and
      morbidity. The very low rate of nasal complains is particularly remarkable.

PMID- 25968327
TI  - Linear accelerator radiosurgery for vestibular schwannomas: Results of medium
      term follow-up.
AB  - BACKGROUND: To examine tumour control, via volume changes, and the complications
      of linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) treatment of
      vestibular schwannomas (VSs) on medium-term follow-up. METHODS: Between September
      2003 and November 2009 fifty consecutive patients with VSs treated with SRS using
      a marginal dose of 12.5 Gy utilizing a LINAC equipped with a micro-multileaf
      collimator were identified. Evaluation included serial magnetic resonance imaging
      (MRI), and neurological and hearing examinations. RESULTS: The median tumour
      volume at treatment was 2.4 (range: 0.24-10.59) cm3. The intracranial diameter of
      the tumours ranged between 7.7 and 28.7 (median: 15.8) mm. Follow-up MRI was
      available for analysis on 49 patients. The median radiological follow-up period
      was 5.8 (range: 1.4-9.2) years. The median tumour volume at last follow-up was
      1.1 (range: 0.03-5.3) cm3. VS decreased in size in 45 (90%) patients, with a
      median reduction in tumour volume of 1.46 (range: 0.06-9.29) cm3 or a median
      tumour size reduction of 59% of the baseline (range: 6-90%) in these patients. VS
      remained stable in 2 patients and increased in size in 2 patients. Only 1 patient
      (2%) required additional intervention (surgery). 15 patients had useful hearing
      pre-treatment; 10 post-treatment pure-tone audiograms of these patients were
      available. 5 (50%) patients still had useful hearing post treatment. Non-auditory
      adverse radiation effects included new (House-Brackmann grade II) or worsened
      facial nerve palsy (House-Brackmann grade II to grade V) in 2 (4%) patients and
      trigeminal sensory disturbance in 2 (4%) patients. CONCLUSIONS: At medium term,
      the vast majority of VSs treated with LINAC-based SRS exhibit tumour shrinkage.
      The slightly higher rate of facial nerve palsy compared with Gamma Knife surgery
      (GKS) results may be related to the learning curve. Other complications were
      similar to reported GKS results for VSs of comparable sizes.

PMID- 25968328
TI  - Follow-up after undersized dilatation of targeted lesions in carotid artery
      stenting.
AB  - BACKGROUND AND PURPOSE: We assessed whether intentional undersized dilatation of
      targeted lesions during carotid artery stenting (CAS) carried a higher risk of in
      stent restenosis (ISR) and correlation to subsequent ischemic stroke in
      qualifying arteries in the follow-up period. METHODS: Consecutive patients
      undergoing CAS between April 2003 and May 2010 were retrospectively reviewed. The
      use of a filter device as a distal embolic protection device (EPD) was first
      approved by Japanese governmental health insurance in April 2008; previously,
      transient balloon occlusion was used off-label. Until March 2008 (Group A), the
      target diameter of balloon dilatation was 80-100% of the normal vessel diameter
      just distal to the stenotic lesion. Moderately undersized dilatation (70-80% of
      the normal vessel diameter) using the distal EPD was adopted in April 2008 (Group
      B) in an attempt to reduce the amount of released plaque debris. RESULTS: We
      analyzed 132 CAS procedures (125 patients) in Group A and 53 CAS procedures (52
      patients) in Group B. The mean follow-up period was 35.4 months (35.3 months in
      Group A and 36.0 months in Group B). Eight lesions (4.3%; 7 in Group A and 1 in
      Group B) developed ISR. None of the patients had symptomatic ISR, and ISR did not
      increase in Group B (odds ratio, 0.34; 95% confidence interval, 0.04-2.86; p =
      0.32). CONCLUSIONS: Undersized dilatation of targeted lesions did not increase
      the risk of developing ISR, and we suggest it as a viable treatment option to
      prevent ischemic events during CAS.

PMID- 25968329
TI  - Clipping of anterior communicating artery aneurysms in the early post-rupture
      stage via transorbital keyhole approach--Chinese neurosurgical experience.
AB  - The anterior communicating artery (AComA) complex is the site at which
      intracranial aneurysms occur most frequently. At present, effective treatments
      for AComA aneurysms are yet to be developed. Here, we present our experience in
      successfully managing AComA aneurysms via the transorbital keyhole approach. A
      total of 52 patients having a history of aneurysm rupture received surgery. All
      patients were assigned a Hunt-Hess grade prior to surgery. The cistern was opened
      to expose the AComA complex using a keyhole approach, and aneurysms were then
      surgically clipped with the assistance of neuroendoscopy or indocyanine green
      angiography. Surgery outcomes were confirmed using computed tomography
      angiography (CTA). Each of the 52 AComA aneurysms was successfully clipped with a
      single operation. Three of these patients experienced intraoperative aneurysm
      rupture. Five had postoperative hydrocephalus which was successfully treated with
      ventriculoperitoneal shunt. All patients survived the surgical procedure. Using
      the Glasgow Outcome Scale scores for evaluation, 39 patients (75.0%) had good
      recovery, 9 (17.3%) had moderate disability, 2 (3.8%) had severe disability, and
      2 patients who had been in preoperative comas (3.8%) remained in a vegetative
      state. During the follow-up period, CTA showed no recurrence of rupture or
      bleeding in all cases. Results of logistic analysis indicated that the
      transorbital keyhole approach was feasible based on the patients' preoperative
      Hunt-Hess grades, which should be considered a priority in using this approach in
      the treatment of ruptured AComA aneurysms. 

PMID- 25968330
TI  - Anterior lumbar interbody fusion versus transforaminal lumbar interbody fusion-
      systematic review and meta-analysis.
AB  - PURPOSE: To assess the clinical and radiographic outcomes and complications of
      anterior lumbar interbody fusion (ALIF) versus transforaminal lumbar interbody
      fusion (TLIF). METHODS: A systematic literature search was conducted from six
      electronic databases. The relative risk and weighted mean difference (WMD) were
      used as statistical summary effect sizes. RESULTS: Fusion rates (88.6% vs. 91.9%,
      P = 0.23) and clinical outcomes were comparable between ALIF and TLIF. ALIF was
      associated with restoration of disk height (WMD, 2.71 mm, P = 0.01), segmental
      lordosis (WMD, 2.35, P = 0.03), and whole lumbar lordosis (WMD, 6.33, P = 0.03).
      ALIF was also associated with longer hospitalization (WMD, 1.8 days, P = 0.01),
      lower dural injury (0.4% vs. 3.8%, P = 0.05) but higher blood vessel injury (2.6%
      vs. 0%, P = 0.04). CONCLUSIONS: ALIF and TLIF appear to have similar success and
      clinical outcomes, with different complication profiles. ALIF may be associated
      with superior restoration of disk height and lordosis, but requires further
      validation in future studies.

PMID- 25968331
TI  - Oncocin Onc72 is efficacious against antibiotic-susceptible Klebsiella pneumoniae
      ATCC 43816 in a murine thigh infection model.
AB  - Oncocins and apidaecins are short proline-rich antimicrobial peptides (PrAMPs)
      representing novel antibiotic drug lead compounds that kill bacteria after
      internalization and inhibition of intracellular targets (e.g. 70S ribosome and
      DnaK). Oncocin Onc72 is highly active against Gram-negative bacteria in vitro and
      in vivo protecting mice in systemic infection models with Escherichia coli and
      KPC-producing Klebsiella pneumoniae. Here we studied its efficacy in a murine
      thigh infection model using meropenem as antibiotic comparator that had a 44-fold
      higher molar in vitro activity than Onc72. Male CD1 mice were rendered
      neutropenic using cyclophosphamide for four days before intramuscular infection
      with K. pneumoniae ATCC 43816. After 75 min oncocin Onc72 or the antibiotic
      comparator meropenem were administered subcutaneously with 100 mg (43 umol) and
      25 mg (65 umol) per kg of body weight, respectively, six times every 75 min.
      Onc72 and meropenem administered subcutaneously reduced the thigh tissue burden
      of K. pneumoniae ATCC 43816 in neutropenic mice significantly by 4.14 and 4.65 a
      log10 cfu/g, respectively. The bacterial counts were ~0.5 and ~1 log10 below the
      pre-treatment burden, respectively, indicating bactericidal effects for both
      compounds. Thus, Onc72 was as efficacious as meropenem in vivo despite its much
      lower in vitro activity determined according to CLSI standard antimicrobial
      activity tests.

PMID- 25968332
TI  - Smoking prevalence and its influence on disease course and surgery in Crohn's
      disease and ulcerative colitis.
AB  - BACKGROUND: Smoking demonstrates divergent effects in Crohn's disease (CD) and
      ulcerative colitis (UC). Smoking frequency is greater in CD and deleterious to
      its disease course. Conversely, UC is primarily a disease of nonsmokers and ex
      smokers, with reports of disease amelioration in active smoking. AIM: To
      determine the prevalence of smoking and its effects on disease progression and
      surgery in a well-characterised cohort of inflammatory bowel diseases (IBD)
      patients. METHODS: Patients with smoking data of the Sydney IBD Cohort were
      included. Demographic, phenotypic, medical, surgical and hospitalisation data
      were analysed and reported on the basis of patient smoking status. RESULTS: 1203
      IBD patients were identified comprising 626 CD and 557 UC with 6725 and 6672
      patient-years of follow-up, respectively. CD patients were more likely to smoke
      than UC patients (19.2% vs. 10.2%, P < 0.001). A history of smoking in CD was
      associated with an increased proportional surgery rate (45.8% vs. 37.8%, P =
      0.045), requirement for IBD-related hospitalisation (P = 0.009) and incidence of
      peripheral arthritis (29.8% vs. 22.0%, P = 0.027). Current smokers with UC
      demonstrated reduced corticosteroid utilisation (24.1% vs. 37.5%, P = 0.045), yet
      no reduction in the rates of colectomy (3.4% vs. 6.6%, P = 0.34) or hospital
      admission (P = 0.25) relative to nonsmokers. Ex-smokers with UC required
      proportionately greater immunosuppressive (36.2% vs. 26.3%, P = 0.041) and
      corticosteroid (43.7% vs. 34.5%, P = 0.078) therapies compared with current and
      never smokers. CONCLUSIONS: This study confirms the detrimental effects of
      smoking in CD, yet failed to demonstrate substantial benefit from smoking in UC.
      These data should encourage all patients with IBD to quit smoking.

PMID- 25968333
TI  - Toward establishing a morphological and ultrastructural characterization of
      proembryogenic masses and early somatic embryos of Araucaria angustifolia (Bert.)
      O. Kuntze.
AB  - Somatic embryogenesis is a morphogenetic route useful for the study of embryonic
      development, as well as the large-scale propagation of endangered species, such
      as the Brazilian pine (Araucaria angustifolia). In the present study, we
      investigated the morphological and ultrastructural organization of A.
      angustifolia somatic embryo development by means of optical and electron
      microscopy. The proembryogenic stage was characterized by the proliferation of
      proembryogenic masses (PEMs), which are cellular aggregates composed of
      embryogenic cells (ECs) attached to suspensor-like cells (SCs). PEMs proliferate
      through three developmental stages, PEM I, II, and III, by changes in the number
      of ECs and SCs. PEM III-to-early somatic embryo (SE) transition was characterized
      by compact clusters of ECs growing out of PEM III, albeit still connected to it
      by SCs. Early SEs showed a dense globular embryonic mass (EM) and suspensor
      region (SR) connected by embryonic tube cells (TCs). By comparison, early somatic
      and zygotic embryos showed similar morphology. ECs are round with a large
      nucleus, nucleoli, and many cytoplasmic organelles. In contrast, TCs and SCs are
      elongated and vacuolated with cellular dismantling which is associated with
      programmed cell death of SCs. Abundant starch grains were observed in the TCs and
      SCs, while proteins were more abundant in the ECs. Based on the results of this
      study, a fate map of SE development in A. angustifolia is, for the first time,
      proposed. Additionally, this study shows the cell biology of SE development of
      this primitive gymnosperm which may be useful in evolutionary studies in this
      area.

PMID- 25968334
TI  - Effector lymphocyte-induced lymph node-like vasculature enables naive T-cell
      entry into tumours and enhanced anti-tumour immunity.
AB  - The presence of lymph node (LN)-like vasculature in tumours, characterized by
      expression of peripheral node addressin and chemokine CCL21, is correlated with T
      cell infiltration and positive prognosis in breast cancer and melanoma patients.
      However, mechanisms controlling the development of LN-like vasculature and how it
      might contribute to a beneficial outcome for cancer patients are unknown. Here we
      demonstrate that LN-like vasculature is present in murine models of melanoma and
      lung carcinoma. It enables infiltration by naive T cells that significantly delay
      tumour outgrowth after intratumoral activation. Development of this vasculature
      is controlled by a mechanism involving effector CD8 T cells and NK cells that
      secrete LTalpha3 and IFNgamma. LN-like vasculature is also associated with
      organized aggregates of B lymphocytes and gp38(+) fibroblasts, which resemble
      tertiary lymphoid organs that develop in models of chronic inflammation. These
      results establish LN-like vasculature as both a consequence of and key
      contributor to anti-tumour immunity. 

PMID- 25968335
TI  - Fish Oil and Olive Oil Supplementation in Late Pregnancy and Lactation
      Differentially Affect Oxidative Stress and Inflammation in Sows and Piglets.
AB  - This study was conducted to compare the effects of fish oil and olive oil
      supplementation in late pregnancy and during lactation on oxidative stress and
      inflammation in sows and their piglets. A total of 24 sows were fed a basal diet
      supplemented with additional corn starch (CON), fish oil (FO) or olive oil (OO).
      Sows fed an OO diet during late gestation had a higher piglet birth weight
      compared with CON-fed and FO-fed sows (P < 0.05). Furthermore, sows from the OO
      group had a higher milk fat content than sows from CON and FO groups, and a lower
      pre-weaning mortality of piglets was observed in the OO group (P < 0.05).
      Maternal FO supplementation resulted in increased malondialdehyde concentration
      in sow plasma, colostrum, milk and piglet plasma than in CON and OO groups (P <
      0.05). However, an increased total antioxidant capacity (T-ACC) and activities of
      glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD) were also
      observed in the FO group (P < 0.05). Sows fed an OO diet had significantly
      decreased interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis
      factor-alpha (TNF-alpha) concentrations in milk compared with CON and FO fed sows
      (P < 0.05). Moreover, lower plasma IL-1beta and TNF-alpha levels were observed in
      piglets from the OO group compared with the CON group (P < 0.05). Collectively,
      these results suggest that an OO diet is most beneficial in late gestation and
      during lactation in sows. However, FO increases the susceptibility to oxidative
      stress in sows and piglets. 

PMID- 25968337
TI  - Hypoxia-driven sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2)
      downregulation depends on low-density lipoprotein receptor-related protein 1
      (LRP1)-signalling in cardiomyocytes.
AB  - The maintenance of sarcoplasmic reticulum Ca(2+) ATPase (SERCA2) activity is
      crucial for cardiac function and SERCA2 is dramatically reduced in the heart
      exposed to hypoxic/ischemic conditions. Previous work from our group showed that
      hypoxia upregulates the phosphorylated form of the Ca(2+)-dependent nonreceptor
      protein tyrosine kinase (PTK) proline-rich tyrosine kinase 2 (pPyk2) protein
      levels in a low-density lipoprotein receptor-related protein (LRP1)-dependent
      manner. Pyk2 in turn may modulate SERCA2 in cardiomyocytes although this remains
      controversial. We therefore aimed to investigate the role of LRP1 on hypoxia
      induced SERCA2 depletion in cardiomyocytes and to establish LRP1 signalling
      mechanisms involved. Western blot analysis showed that hypoxia reduced SERCA2
      concomitantly with a sustained increase in LRP1 and pPyk2 protein levels in HL-1
      cardiomyocytes. By impairing hypoxia-induced Pyk2 phosphorylation and HIF-1alpha
      accumulation, LRP1 deficiency prevented SERCA2 depletion and reduction of the
      sarcoplasmic reticulum calcium content in cardiomyocytes. Moreover, the
      inhibition of Pyk2 phosphorylation (with the Src-family inhibitor PP2) or the
      specific silencing of Pyk2 (with siRNA-anti Pyk2) preserved low HIF-1alpha and
      high SERCA2 levels in HL-1 cardiomyocytes exposed to hypoxia. We determined that
      the LRP1/Pyk2 axis represses SERCA2 mRNA expression via HIF-1alpha since HIF
      1alpha overexpression abolished the protective effect of LRP1 deficiency on
      SERCA2 depletion. Our findings show a crucial role of LRP1/Pyk2/HIF-1alpha in
      hypoxia-induced cardiomyocyte SERCA2 downregulation, a pathophysiological process
      closely associated with heart failure. 

PMID- 25968338
TI  - Detection of Two Drug-Resistance Mutants of the Cytomegalovirus by High
      Resolution Melting Analysis.
AB  - BACKGROUND: Human cytomegalovirus (CMV) is an opportunistic pathogen that can be
      treated with ganciclovir. Mutations in the UL97 gene of CMV render the virus
      ganciclovir resistance. These include H520Q and C603W mutations, against which we
      developed a novel genotyping assay for their identification. METHODS: PCR
      reactions were performed to amplify fragments of the UL97 gene containing H520Q
      or C603W mutations. High resolution melting analysis (HRMA) coupled with
      unlabeled DNA probes was employed to identify the shift in melting temperature of
      the probe-template complex, which reflexes the presence of point mutations.
      RESULTS: Melting point analysis performed on the dimeric DNA of PCR products of
      UL97 gene could not identify mutations in the gene. When coupled to unlabeled
      probes, point mutations in UL97 can be identified by analyzing the melting curve
      of probe-template complex. When WT and mutant UL97 DNAs were mixed together to
      mimic heterogeneous viral population in clinical samples, the genotyping assay is
      sensitive enough to detect H520Q and C603W mutants that constitute 10% of total
      DNA input. CONCLUSION: Probe-based HRMA is effective in detecting H520Q and C603W
      mutations in the UL97 gene of CMV.

PMID- 25968336
TI  - Functional brown adipose tissue limits cardiomyocyte injury and adverse
      remodeling in catecholamine-induced cardiomyopathy.
AB  - Brown adipose tissue (BAT) has well recognized thermogenic properties mediated by
      uncoupling protein 1 (UCP1); more recently, BAT has been demonstrated to modulate
      cardiovascular risk factors. To investigate whether BAT also affects myocardial
      injury and remodeling, UCP1-deficient (UCP1(-/-)) mice, which have dysfunctional
      BAT, were subjected to catecholamine-induced cardiomyopathy. At baseline, there
      were no differences in echocardiographic parameters, plasma cardiac troponin I
      (cTnI) or myocardial fibrosis between wild-type (WT) and UCP1(-/-) mice.
      Isoproterenol infusion increased cTnI and myocardial fibrosis and induced left
      ventricular (LV) hypertrophy in both WT and UCP1(-/-) mice. UCP1(-/-) mice also
      demonstrated exaggerated myocardial injury, fibrosis, and adverse remodeling, as
      well as decreased survival. Transplantation of WT BAT to UCP1(-/-) mice prevented
      the isoproterenol-induced cTnI increase and improved survival, whereas UCP1(-/-)
      BAT transplanted to either UCP1(-/-) or WT mice had no effect on cTnI release.
      After 3 days of isoproterenol treatment, phosphorylated AKT and ERK were lower in
      the LV's of UCP1(-/-) mice than in those of WT mice. Activation of BAT was also
      noted in a model of chronic ischemic cardiomyopathy, and was correlated to LV
      dysfunction. Deficiency in UCP1, and accompanying BAT dysfunction, increases
      cardiomyocyte injury and adverse LV remodeling, and decreases survival in a mouse
      model of catecholamine-induced cardiomyopathy. Myocardial injury and decreased
      survival are rescued by transplantation of functional BAT to UCP1(-/-) mice,
      suggesting a systemic cardioprotective role of functional BAT. BAT is also
      activated in chronic ischemic cardiomyopathy.

PMID- 25968339
TI  - Independent Proteolytic Activities Control the Stability and Size of Drosophila
      Inhibitor of Apoptosis 2 Protein.
AB  - The Drosophila immune deficiency pathway defends many bacterial pathogens and
      bears striking molecular similarities to the mammalian tumor necrosis factor
      signal transduction pathway. Orthologous inhibitors of apoptosis ubiquitin
      ligases act at a proximal stage of both responses to coordinate the assembly of
      signal transduction platforms that shape host immune responses. Despite the
      importance of inhibitor of apoptosis proteins within evolutionarily conserved
      innate immune responses, we know relatively little about the cellular machinery
      that controls inhibitor of apoptosis activity. In this study, we examined the
      molecular basis for inhibitor of apoptosis 2 protein regulation in the immune
      deficiency pathway. Our studies identified two distinct proteolytic events that
      determine the stability and composition of cellular inhibitor of apoptosis 2
      protein pools. We found that apoptotic caspase activity cleaves inhibitor of
      apoptosis 2 at an N-terminal aspartate to generate a truncated protein that
      retains the ability to interact with immune deficiency pathway members. We also
      showed that a C-terminal ubiquitin ligase activity within inhibitor of apoptosis
      2 directs the proteasomal destruction of full-length and truncated inhibitor of
      apoptosis 2 isoforms. These studies add to our appreciation of the regulation of
      innate immunity and suggest potential links between apoptotic caspases and innate
      defenses. 

PMID- 25968340
TI  - Oral Propranolol: A New Treatment for Infants with Retinopathy of Prematurity?
AB  - INTRODUCTION: Oral propranolol has improved the treatment of infantile
      hemangiomas, and a pediatric oral solution of propranolol has recently been
      licensed in the USA and Europe. In very preterm infants, infantile hemangiomas
      are associated with the occurrence of retinopathy of prematurity (ROP), and both
      diseases share a peculiar time course, featuring a lag phase after birth followed
      by rapid growth and then gradual regression. OBJECTIVES: To identify clinical
      studies evaluating the use of oral propranolol in preterm infants with ROP.
      RESULTS: Two small bicentric, pilot, randomized controlled trials found a
      nonsignificant reduction of ROP requiring intervention by laser treatment or
      bevacizumab injection of similar magnitude. Together, 6 of 35 (17%) infants who
      had been receiving oral propranolol underwent ROP intervention, as opposed to 14
      of 36 (39%) controls (relative risk 0.42, 95% CI: 0.15-1.16). Randomized
      controlled trials are ongoing that investigate early preventive oral propranolol
      starting at 1 week of age and propranolol eye drops in preterm infants with stage
      2 ROP. CONCLUSION: Further, large interventional studies are required to
      determine the clinical benefit-risk ratio of oral propranolol to prevent vision
      threatening ROP in very preterm infants.

PMID- 25968341
TI  - Synergistic Cu-amine catalysis for the enantioselective synthesis of chiral
      cyclohexenones.
AB  - An unprecedented utilization of 1,3-acetonedicarboxylic acid as a 1,3-bis-pro
      nucleophile and a reactive acetone surrogate in enantioselective catalysis has
      been reported. By synergistically activating the ketodiacid by copper catalysis
      and an alpha,beta-unsaturated aldehyde by amine catalysis, an efficient domino di
      decarboxylative Michael/aldol/dehydration sequence takes place leading to
      valuable chiral cyclohexenones in one single operation in 94 to 99% ee. 

PMID- 25968342
TI  - Proposed Minimum Rates of Surgery to Support Desirable Health Outcomes: An
      Observational Study Based on Three Strategies.
AB  - BACKGROUND: The global volume of surgery is estimated at 312.9 million operations
      annually, but rates of surgery vary dramatically. Identifying surgical rates
      associated with improved health outcomes would be useful for benchmarking and
      targeted health system strengthening. METHODS: We identified rates of surgery
      associated with a life expectancy (LE) of 74-75 years, a maternal mortality ratio
      (MMR) of less than or equal to 100 per 100,000 live births, and the estimated
      need for surgery in the seven global burden of disease (GBD) super-regions based
      on the prevalence of surgical conditions. We compared our findings to surgical
      rates from Chile, China, Costa Rica, and Cuba ("4C"), countries with moderate
      resources but high health outcomes. RESULTS: The median surgical rates associated
      with LE of 74-75 years (N = 17) and MMR below 100 (N = 109) are 4392 (IQR 2897
      4873) and 5028 (IQR 4139-6778) operations per 100,000 people annually,
      respectively. The mean surgical rate estimated for the seven super-regions was
      4723 (95% CI 3967-5478) operations per 100,000 people annually. The "4C"
      countries had a mean surgical rate of 4344 (95% CI 2620-6068) operations per
      100,000 people annually. Thirteen of the twenty-one GBD regions, accounting for
      78% of the world's population, do not achieve rates of surgery at the lowest end
      of this range. CONCLUSIONS: We identified a narrow range of surgical rates
      associated with important health indicators. This target range can be used for
      benchmarking of surgical services, and as part of a policy aimed at strengthening
      health care systems and surgical capacity.

PMID- 25968343
TI  - Pseudohalide-induced moisture tolerance in perovskite CH3 NH3 Pb(SCN)2 I thin
      films.
AB  - Two pseudohalide thiocyanate ions (SCN(-) ) have been used to replace two iodides
      in CH3 NH3 PbI3 , and the resulting perovskite material was used as the active
      material in solar cells. In accelerated stability tests, the CH3 NH3 Pb(SCN)2 I
      perovskite films were shown to be superior to the conventional CH3 NH3 PbI3 films
      as no significant degradation was observed after the film had been exposed to air
      with a relative humidity of 95 % for over four hours, whereas CH3 NH3 PbI3 films
      degraded in less than 1.5 hours. Solar cells based on CH3 NH3 Pb(SCN)2 I thin
      films exhibited an efficiency of 8.3 %, which is comparable to that of CH3 NH3
      PbI3 based cells fabricated in the same way. 

PMID- 25968344
TI  - Interspecific variation in functional traits of oak seedlings (Quercus ilex,
      Quercus trojana, Quercus virgiliana) grown under artificial drought and fire
      conditions.
AB  - To face summer drought and wildfire in Mediterranean-type ecosystems, plants
      adopt different strategies that involve considerable rearrangements of biomass
      allocation and physiological activity. This paper analyses morphological and
      physiological traits in seedlings of three oak species (Quercus ilex, Quercus
      trojana and Quercus virgiliana) co-occurring under natural conditions. The aim of
      this study was to evaluate species-specific characteristics and the response of
      these oak seedlings to drought stress and fire treatment. Seedlings were kept in
      a growth chamber that mimicked natural environmental conditions. All three
      species showed a good degree of tolerance to drought and fire treatments.
      Differences in specific biomass allocation patterns and physiological traits
      resulted in phenotypic differences between species. In Q. ilex, drought tolerance
      depended upon adjustment of the allocation pattern. Q. trojana seedlings
      undergoing mild to severe drought presented a higher photosystem II (PSII)
      efficiency than control seedlings. Moreover, Q. trojana showed a very large root
      system, which corresponded to higher soil area exploitation, and bigger leaf
      midrib vascular bundles than the other two species. Morphological and
      physiological performances indicated Q. trojana as the most tolerant to drought
      and fire. These characteristics contribute to a high recruitment potential of Q.
      trojana seedlings, which might be the reason for the dominance of this species
      under natural conditions. Drought increase as a result of climate change is
      expected to favour Q. trojana, leading to an increase in its spatial
      distribution. 

PMID- 25968345
TI  - Effect of treatment with baicalein on the intracerebral tumor growth and survival
      of orthotopic glioma models.
AB  - Baicalein, a widely used Chinese herbal medicine, has been proved as a promising
      chemopreventive compound for many cancers. The aim of this work was to assess the
      anti-tumor effect of baicalein in the orthotopic glioma models. It was found that
      treatment of mice with U87 gliomas with baicalein (20 and 40 mg/kg/day, i.p.)
      significantly inhibited the intracerebral tumor growth and prolonged the
      survival. Furthermore, treatment with baicalein suppressed cell proliferation,
      promoted apoptosis, and arrested cell cycle in U87 gliomas. In addition,
      treatment with baicalein reduced tumor permeability, attenuated edema of tumors
      and brains, and improved tight junctions in gliomas. Finally, treatment with
      baicalein reduced the expression of HIF-1alpha, VEGF, and VEGFR2 in U87 gliomas.
      In addition, treatment with baicalein also markedly suppressed tumor growth and
      prolonged the survival of rats with 9L gliomas. In conclusion, baicalein has an
      obvious anti-tumor activity in the orthotopic glioma models. Our results
      suggested that treatment with baicalein might be an effective therapy for
      recurrent malignant brain cancers through suppressing tumor growth and
      alleviating edema. 

PMID- 25968346
TI  - Low grade astrocytoma in children under the age of three years: a report from the
      Canadian pediatric brain tumour consortium.
AB  - In children under the age of 3 years, the most common solid tumors are brain
      tumors. Low grade astrocytomas represent 30-40 % of brain tumours in this age
      group. This study reviewed the incidence, characteristics, therapy, and outcome
      of children less than 36 months of age diagnosed with a low grade astrocytoma
      from 1990 to 2005 in Canada. A data bank was established using data collected
      from Canadian pediatric oncology centers on children less than age 3 diagnosed
      with brain tumors between 1990 and 2005. Cases of low grade astrocytoma were
      extracted from this data bank and their characteristics summarized. From the 579
      cases in the data bank, 153 cases of low grade astrocytoma (26 %) were
      identified. The mean duration of symptoms prior to presentation was 13 weeks, and
      53 % of patients underwent a greater than 90 % resection of their tumor, while 30
      % underwent 10-90 % resection. Seventy-one percent of patients received no
      further therapy after surgery and of the 45 who received therapy following
      surgery, 43 received chemotherapy, and 5 received radiation therapy. Sixty-eight
      patients had recurrence or progression of their tumor. Eighty-seven percent of
      patients were alive at the time of the survey with a 2 year survival rate of 95.3
      +/- 1.8 %, 5 year survival rate of 93.1 +/- 2.1 % and 10 year survival rate of
      89.1 +/- 2.8 %. The 5 year survival rate for Canadian children less than 36
      months of age with a low grade astrocytoma was 93.0 +/- 2.8 % which is similar to
      that for older children with this tumor. 

PMID- 25968347
TI  - Metabolism of chicoric acid by rat liver microsomes and bioactivity comparisons
      of chicoric acid and its metabolites.
AB  - Chicoric acid has recently become a hot research topic due to its potent
      bioactivities. However, there are few studies relevant to this acid's
      pharmacokinetic characteristics and the pharmacological activities of its
      metabolites. To compare the abilities of chicoric acid and its metabolites in
      scavenging free radicals and their effects on the viability of 3T3-L1
      preadipocytes, an in vitro study of the metabolism of chicoric acid in rat liver
      microsomes was performed using liquid tandem mass spectrometry (HPLC-MS/MS). The
      results indicated that caffeic acid and caftaric acid were the hepatic phase I
      metabolites of chicoric acid. These three compounds had strong capacities for
      scavenging free radicals and had been demonstrated to increase intracellular ROS
      levels in 3T3-L1 preadipocytes, thereby reducing cell vitality. Finally, the
      pharmacological activities of chicoric acid were significantly stronger than
      those of its metabolites within a certain concentration range.

PMID- 25968348
TI  - Benefits of using the cell block method to determine the discordance of the
      HR/HER2 expression in patients with metastatic breast cancer.
AB  - BACKGROUND: The discordance of the hormone receptor (HR) and human epidermal
      growth factor receptor 2 (HER2) expressions between primary cancer and metastatic
      lesions is an important issue when selecting the optimal treatments for patients
      with metastatic breast cancer. A rebiopsy for the metastatic cancer is
      recommended before selecting the treatment; however, it is not easy to take a
      tissue sample for all metastatic lesions. Fine needle aspiration cytology (FNA)
      for regional lymph nodes and aspiration for pleural effusions or ascites are less
      invasive procedures to obtain the necessary samples to examine the HR/HER2
      expression. These cytologic materials are able to be stained as a tissue sample
      using the cell block method. PATIENTS: We examined the HR/HER2 expression of 20
      patients with breast cancer (8 with synchronous metastases and 12 with
      metachronous metastases) using the cell block method. Among 8 patients with
      synchronous metastases, 7 patients with axillary lymph node (LN) metastasis were
      examined by fine needle aspiration (FNA), and one patient with pleural metastases
      was analyzed for the aspirated fluid. While in 12 patients with metachronous
      metastases, 7 patients were examined for their pleural effusion, 3 patients were
      examined for regional lymph node metastases, and 1 patient were examined for
      aspirated ascites. We compared the HR/HER expression between primary cancer and
      metastatic lesion in 17 patients (5 cases of 8 synchronous metastases, and all of
      12 metachronous metastases). RESULTS: Discordance of HR was seen in 4 of 17
      patients (24 %). Three cases with axillary LN metastasis (2 cases with
      synchronous metastases and one with metachronous metastasis) showed negative
      change of ER. Negative change of HER2 expression was seen in one patient with
      ascites caused by peritoneal dissemination. CONCLUSIONS: Cytology materials are
      easily obtained by FNA for LN metastases and aspiration for malignant effusions
      and analyzed for HR/HER2 expression using cell block method. We should take
      advantage of cell block analysis to determine the discordance of the HR/HER2
      expression to select the optimal treatment for metastatic breast cancer.

PMID- 25968349
TI  - Control of pertussis in infants: time has finally come?
AB  - Despite the success of routine immunization programs against pertussis worldwide,
      control of the disease in young infants has never been achieved. The greatest
      risk of disease, hospitalization and death occur in infants, who are too young to
      have received the primary pertussis immunization course. Different interventions
      to provide indirect protection to infants were recommended, including vaccination
      programs with Tdap for adolescents, adults, postpartum women and household
      contacts of infants, but all of them failed to effectively control the disease in
      infants. Based on the successful experience of maternal tetanus vaccination, and
      more recently influenza vaccination, maternal Tdap vaccine has been universally
      recommended since 2011/2012 in several countries to prevent pertussis in infants.
      The recent publication of data on the uptake, safety and effectiveness of these
      programs, as well as impact on disease rates in infants is encouraging,
      anticipating the possibility to at last control pertussis in this vulnerable age
      group. 

PMID- 25968350
TI  - Reply to Pang et al. letter: Multifaceted roles of platelets in the prognosis of
      patients with hepatoma.

PMID- 25968351
TI  - Aldosterone Signals the Onset of Depressive Behaviour in a Female Rat Model of
      Depression along with SSRI Treatment Resistance.
AB  - Depression is a serious condition that occurs more frequently in women and is
      often associated with treatment resistance. The main hypotheses of this study are
      that (a) aldosterone is an early marker of depression onset and (b) a tryptophan
      (TRP) depletion model of depression previously validated in male rats is
      treatment resistant in females. To explore possible underlying mechanisms, we
      have focused on factors shown to be altered in patients with treatment-resistant
      depression. Female Sprague-Dawley rats were treated with a control or low-TRP
      containing diet for various time periods up to 21 days. The results show that
      aldosterone secretion increased after 4 days of TRP depletion and prior to
      corticosterone. Optimal effects of TRP depletion occurred at 14 days. In addition
      to neurochemical and behavioural changes observed previously in males, TRP
      depletion in females was associated with a significant decline in serum magnesium
      concentrations, increased serum interleukin-6, enhanced gene expression of orexin
      A in the frontal cortex and induced a rise in N-methyl-D-aspartate (NMDA)
      receptor Bmax in the amygdala. Depression-like behaviour, NMDA receptor
      upregulation, enhancement of the kynurenine-to-kynurenic acid ratio and magnesium
      were resistant to paroxetine treatment (10 mg/kg/day in drinking water for 14
      days). In conclusion, aldosterone may represent an important early marker for the
      onset of depression-like behaviour. With respect to treatment resistance, the
      underlying mechanisms may involve pro-inflammatory cytokines, the kynurenine
      pathway, magnesium, glutamate neurotransmission and the orexin pathway. This
      model of treatment-resistant depression may be useful for the future development
      of new compounds with novel antidepressant properties.

PMID- 25968352
TI  - Analyzing multiple cross-sectional samples with application to hospitalization
      time after surgeries.
AB  - Repeated cross-sectional sampling results in multiple biased samples with
      possibly different weight functions. The standard non-parametric maximum
      likelihood estimator for the lifetime distribution of interest solves a set of
      nonlinear equations, and its variance has a very complicated form. We suggest a
      simple closed-form estimator for the case where entrances to the population of
      interest follow a Poisson model. The variance of the estimator and confidence
      intervals are easily calculated. Our motivating example concerns a series of
      cross-sectional surveys conducted in Israeli hospitals. We discuss the bias
      mechanism in our data and suggest a simple design plan that provides valid
      estimators even when the weight functions are unknown. The new method is applied
      to estimate the distribution of hospitalization time after bowel and hernia
      surgeries.

PMID- 25968355
TI  - [Cephalomedullary implant using an extension table].

PMID- 25968354
TI  - [Distal clavicle fractures. Classifications and management].
AB  - BACKGROUND: Fractures of the distal third of the clavicle represent 10-30% of all
      clavicle fractures . Frequently, these fractures result in instability due to a
      combination of bony and ligamentous injury. Thus, assessment of the stability is
      essential for adequate treatment of these fractures. AIM: This article presents a
      review of the different classification systems for distal clavicle fractures with
      respect to anatomical and functional factors to allow for comprehensive
      assessment of stability. Furthermore, the different treatment options for each
      fracture type are analyzed. RESULTS AND DISCUSSION: Fractures to the distal third
      of the clavicle without instability can be treated conservatively with
      satisfactory outcome. In contrast, instability may result in symptomatic non
      union under conservative treatment; therefore, distal clavicle fractures with
      instability should be treated operatively with respect to the functional demands
      of the patient. Operative treatment with locked plating in combination with
      coracoclavicular fixation results in excellent functional results.
      Arthroscopically assisted fracture fixation may be beneficial in terms of a
      minimally invasive approach as well as assessment and treatment of associated
      glenohumeral lesions.

PMID- 25968356
TI  - Environmental Staphylococcus aureus contamination in a Tunisian hospital.
AB  - One hundred hospital environment samples were obtained in 2012 in a Tunisian
      hospital and tested for Staphylococcus aureus recovery. Antimicrobial resistance
      profile and virulence gene content were determined. Multilocus-sequence-typing
      (MLST), spa-typing, agr-typing and SmaI-pulsed-field gel electrophoresis (PFGE)
      were performed. Two methicillin-resistant S. aureus (MRSA) isolates typed as:
      ST247-t052-SCCmecI-agrI were recovered from the intensive care unit (ICU). Ten
      samples contained methicillin-susceptible S. aureus (MSSA) and these samples were
      collected in different services, highlighting the presence of the tst gene
      encoding the toxic shock syndrome toxin as well as the lukED, hla, hlb, hld and
      hlgv virulence genes in some of the isolates. In conclusion, we have shown that
      the hospital environment could be a reservoir contributing to dissemination of
      virulent S. aureus and MRSA.

PMID- 25968357
TI  - Freeze gelated porous membranes for periodontal tissue regeneration.
AB  - Guided tissue regeneration (GTR) membranes have been used for the management of
      destructive forms of periodontal disease as a means of aiding regeneration of
      lost supporting tissues, including the alveolar bone, cementum, gingiva and
      periodontal ligaments (PDL). Currently available GTR membranes are either non
      biodegradable, requiring a second surgery for removal, or biodegradable. The
      mechanical and biofunctional limitations of currently available membranes result
      in a limited and unpredictable treatment outcome in terms of periodontal tissue
      regeneration. In this study, porous membranes of chitosan (CH) were fabricated
      with or without hydroxyapatite (HA) using the simple technique of freeze gelation
      (FG) via two different solvents systems, acetic acid (ACa) or ascorbic acid
      (ASa). The aim was to prepare porous membranes to be used for GTR to improve
      periodontal regeneration. FG membranes were characterized for ultra-structural
      morphology, physiochemical properties, water uptake, degradation, mechanical
      properties, and biocompatibility with mature and progenitor osteogenic cells.
      Fourier transform infrared (FTIR) spectroscopy confirmed the presence of
      hydroxyapatite and its interaction with chitosan. MUCT analysis showed membranes
      had 85-77% porosity. Mechanical properties and degradation rate were affected by
      solvent type and the presence of hydroxyapatite. Culture of human osteosarcoma
      cells (MG63) and human embryonic stem cell-derived mesenchymal progenitors (hES
      MPs) showed that all membranes supported cell proliferation and long term matrix
      deposition was supported by HA incorporated membranes. These CH and HA composite
      membranes show their potential use for GTR applications in periodontal lesions
      and in addition FG membranes could be further tuned to achieve characteristics
      desirable of a GTR membrane for periodontal regeneration. 

PMID- 25968359
TI  - Calibration optimization of laser-induced deflection signal for measuring
      absorptance of laser components.
AB  - Different configurations of the laser-induced deflection (LID) technique have
      been developed recently to measure the absolute bulk and coating absorption of
      laser components directly. In order to obtain the absolute absorptance value of
      the surface or coating of a laser component, a reference sample with the same
      geometry and material as the test sample and with resist heating mounted on the
      surface of the reference sample was employed to calibrate LID signals. Due to the
      difference in the excitation approaches in measuring LID signals of the test and
      reference samples (laser beam irradiation versus surface resist heating), this
      calibration procedure may bring significant errors in the determination of the
      absorptance of the test sample. In this paper, theoretical models describing the
      temperature rise distributions within a test sample excited with flat-top beam
      irradiation and within a reference sample excited with surface resist heating are
      developed. Based on these temperature models and the finite-element analysis
      method, the LID signals used to determine the absorptance of the surface or
      coating of a laser component and the corresponding calibration error are
      analyzed. The computation results show that the calibration error depends largely
      on the probe beam position for normal or transverse LID signals and may be
      minimized by optimizing the probe beam geometry. 

PMID- 25968358
TI  - Setup and validation of shake-flask procedures for the determination of partition
      coefficients (logD) from low drug amounts.
AB  - Several procedures based on the shake-flask method and designed to require a
      minimum amount of drug for octanol-water partition coefficient determination have
      been established and developed. The procedures have been validated by a 28
      substance set with a lipophilicity range from -2.0 to 4.5 (logD7.4). The
      experimental partition is carried out using aqueous phases buffered with
      phosphate (pH 7.4) and n-octanol saturated with buffered water and the analysis
      is performed by liquid chromatography. In order to have accurate results, four
      procedures and eight different ratios between phase volumes are proposed. Each
      procedure has been designed and optimized (for partition ratios) for a specific
      range of drug lipophilicity (low, regular and high lipophilicity) and solubility
      (high and low aqueous solubility). The procedures have been developed to minimize
      the measurement in the octanolic phase. Experimental logD7.4 values obtained from
      different procedures and partition ratios show a standard deviation lower than
      0.3 and there is a nice agreement when these values are compared with the
      reference literature ones. 

PMID- 25968360
TI  - Modal processing of Hartmann and Shack-Hartmann patterns by means of a least
      squares fitting of the transverse aberrations: erratum.

PMID- 25968361
TI  - Retrieval of temperature from a multiple-channel Rayleigh-scatter lidar using an
      optimal estimation method.
AB  - The measurement of temperature in the middle atmosphere with Rayleigh-scatter
      lidars is an important technique for assessing atmospheric change. Current
      retrieval schemes for this temperature have several shortcomings, which can be
      overcome by using an optimal estimation method (OEM). Forward models are
      presented that completely characterize the measurement and allow the simultaneous
      retrieval of temperature, dead time, and background. The method allows a full
      uncertainty budget to be obtained on a per profile basis that includes, in
      addition to the statistical uncertainties, the smoothing error and uncertainties
      due to Rayleigh extinction, ozone absorption, lidar constant, nonlinearity in the
      counting system, variation of the Rayleigh-scatter cross section with altitude,
      pressure, acceleration due to gravity, and the variation of mean molecular mass
      with altitude. The vertical resolution of the temperature profile is found at
      each height, and a quantitative determination is made of the maximum height to
      which the retrieval is valid. A single temperature profile can be retrieved from
      measurements with multiple channels that cover different height ranges, vertical
      resolutions, and even different detection methods. The OEM employed is shown to
      give robust estimates of temperature, which are consistent with previous methods,
      while requiring minimal computational time. This demonstrated success of lidar
      temperature retrievals using an OEM opens new possibilities in atmospheric
      science for measurement integration between active and passive remote sensing
      instruments. 

PMID- 25968362
TI  - Temperature dependence of a refractive index sensor based on a macrobending micro
      plastic optical fiber.
AB  - We investigate the temperature dependence of a refractive index (RI) sensor based
      on a macrobending micro-plastic optical fiber (m-POF) both theoretically and
      experimentally. The performance of the RI sensor at different temperatures (10
      degrees C-70 degrees C) is measured and simulated over an RI range from 1.33 to
      1.45. It is found that the temperature dependent bending loss and RI measurement
      deviation monotonically change with temperature, and the RI deviation has a
      higher gradient with temperature variation for a higher measured RI. Because of
      the linear trend of temperature dependence of the sensor, it is feasible to
      correct for changes in ambient temperature. 

PMID- 25968363
TI  - Analysis of compressive sensing with optical mixing using a spatial light
      modulator.
AB  - Compressive sensing (CS) in a photonic link has a high potential for acquisition
      of wideband sparse signals. In CS it is necessary to mix the input sparse signal
      with a pseudorandom sequence prior to subsampling. A pulse shaper with a spatial
      light modulator (SLM) can be used in photonic CS as an optical mixer to improve
      the speed of mixing. In this approach, the sparse signal is modulated on a
      chirped optical pulse and the pseudorandom sequence is recorded on the SLM within
      the pulse shaper. The optical mixing in the frequency domain is realized based on
      the principle of frequency-to-time mapping. In this paper, we investigate the
      performance and limitations of photonic CS with an SLM in detail. A theoretical
      model to describe optical mixing based on frequency-to-time mapping is presented.
      We point out that there is an upper limit on the length of the pseudorandom
      sequence recorded on the SLM that can be mixed with the sparse signal due to the
      condition of the far-field approximation of the frequency-to-time mapping. Since
      the length of the pseudorandom sequence is one of the major factors that affect
      the signal recovery performance in CS, this limitation should be fully considered
      in the system design of the CS with optical mixing in the frequency domain. We
      present numerical and experimental results to verify the theoretical findings.
      Discussion on the performance improvement is also presented. 

PMID- 25968364
TI  - Automated construction of monochromatic monitoring strategies.
AB  - We focus our efforts on development of an advanced monochromatic monitoring
      strategy to assist the optical coating engineer in finding a single wavelength or
      a sequence of monitoring wavelengths that meet simultaneously several practical
      demands, namely, specified input and output swing values, specified amplitude of
      a monitoring signal variation, and the distance between trigger point and the
      last signal extremum. Additionally, the most important demand is that the number
      of different monitoring wavelengths must be as small as possible. Manual
      construction of such a monitoring strategy is almost impossible because of a
      large number of conditions to be satisfied. We propose an algorithm that
      automatically generates a monitoring spreadsheet so that all demands can be
      satisfied as closely as possible. We consider six typical design problems and
      obtain a series of solutions for each of them. Then, we provide computational
      simulations of deposition processes assuming that they are controlled by
      monochromatic monitoring with the monitoring strategy generated by our algorithm,
      and we demonstrate how an optical coating engineer can select design solutions
      that exhibit the highest production yields. 

PMID- 25968365
TI  - Transmittance and optical constants of Ca films in the 4-1000  eV spectral range.
AB  - The low expected absorption of Ca in the extreme ultraviolet (EUV) makes it an
      attractive material for multilayers and filters because most materials in nature
      strongly absorb the EUV. Few optical constant data had been reported for Ca. In
      this research, Ca films of various thicknesses were deposited on grid-supported C
      films and their transmittance measured in situ from the visible to the soft x
      rays. The measurement range contains M2,3 and L2,3 absorption edges.
      Transmittance measurements were used to obtain the Ca extinction coefficient k. A
      minimum k of 0.017 was obtained at ~23  eV, which makes Ca a promising low
      absorption material for EUV coatings. A second spectral range of interest for its
      low absorption is below the Ca L3 edge at ~343  eV. Measured k data and
      extrapolations were used to calculate the refractive index n using Kramers-Kronig
      relations. This is the first self-consistent data set on Ca covering a wide
      spectral range including the EUV.

PMID- 25968366
TI  - Influence of ghost coupling points on distributed polarization crosstalk
      measurements in high birefringence fiber and its solution.
AB  - Ghost coupling points in distributed polarization crosstalk measurements adopting
      a white light interferometric method are analyzed under the circumstances of
      anisotropy perturbation induced polarization crosstalk and principal axis
      misalignment induced polarization crosstalk in polarization-maintaining fiber.
      The relationship between the intensities of the ghost coupling points and the
      real crosstalk points, as well as the relationship between their positions, are
      theoretically analyzed and proved by experiment. A simple method has been
      developed to identify the ghost coupling points by using a rotatable half-wave
      plate to adjust the angle between the principal axis of the analyzer and the
      exciting mode propagating in the polarization-maintaining fiber. The experimental
      results have a good agreement with the theoretical results. 

PMID- 25968367
TI  - Three-dimensional graphic physically based simulator of rainbows together with
      the background scene.
AB  - This paper presents a single scattering 3D graphics simulator of rainbows that
      includes the thickness of the rain shaft and the background scenery. The
      simulator is devised so that we can find a good configuration of the sun, the
      viewers, and the volume of water drops in a complicated geometric setting. The
      background-scene geometry and light-reflecting properties are modelled using 3D
      graphics tools. The simulator allows both the light reflected from the background
      surface and the light scattered by water drops to contribute to the final image
      by taking the depth to the background surface into account. The simulator
      generates an image of the rainbow by using the radiative transfer equation (RTE).
      We use ray optics to compute the average scattering cross section and the average
      phase function of particles that are the main parameters of the RTE. Depending on
      the density distribution of the water drops, the rainbow is perceived to be
      translucent, and the background scene is visible through the rainbow. We simulate
      other effects of the variation of the water-dropdensity and the location of the
      viewer, e.g., the visibility of the secondary rainbow, the brightness of the sky
      around the rainbow, the close-up view of the rainbow, and the full-circle
      rainbow. We explain these effects partly by computing the luminance contrasts of
      the primary and secondary bows against their local backgrounds. 

PMID- 25968368
TI  - Pixel size adjustment in coherent diffractive imaging within the Rayleigh
      Sommerfeld regime.
AB  - The reconstruction of the smallest resolvable object detail in digital holography
      and coherent diffractive imaging when the detector is mounted close to the object
      of interest is restricted by the sensor's pixel size. Very high resolution
      information is intrinsically encoded in the data because the effective numerical
      aperture (NA) of the detector (its solid angular size as subtended at the object
      plane) is very high. The correct physical propagation model to use in the
      reconstruction process for this setup should be based on the Rayleigh-Sommerfeld
      diffraction integral, which is commonly implemented via a convolution operation.
      However, the convolution operation has the drawback that the pixel size of the
      propagation calculation is preserved between the object and the detector, and so
      the maximum resolution of the reconstruction is limited by the detector pixel
      size, not its effective NA. Here we show that this problem can be overcome via
      the introduction of a numerical spherical lens with adjustable magnification.
      This approach enables the reconstruction of object details smaller than the
      detector pixel size or of objects that extend beyond the size of the detector. It
      will have applications in all forms of near-field lensless microscopy. 

PMID- 25968369
TI  - Long-term comparisons of UV index values derived from a NILU-UV instrument, NWS,
      and OMI in the New York area.
AB  - A comparison is presented of UV index (UVI) values obtained under different cloud
      conditions from a Norwegian Institute for Air Research UV (NILU-UV) instrument,
      the ozone monitoring instrument (OMI) onboard the Aura satellite, and the
      National Weather Service (NWS) model for the time period of 2010-2014. The NILU
      UV irradiance meter is a ground-based, multi-channel, moderate bandwidth filter
      instrument. UVI values derived from measurements by a NILU-UV instrument deployed
      in the New York area (40.74 degrees N, -74.03 degrees E) to monitor the erythemal
      UV radiation from 2010 to present is compared to UVI values derived from OMI
      measurements and predicted by the NWS model. OMI overestimated the UVI values by
      13.06% for all cloud conditions compared with the UVI values derived from
      measurements by the NILU-UV instrument. The heavier the cloud cover, the higher
      the overestimation. The mean relative difference between the UVI derived from the
      NWS model and from NILU-UV measurements was 11.54%. The UVI prediction by NWS was
      also overestimated under cloudy conditions. Under overcast conditions the NWS
      predictions of UVI values differ significantly from those derived from NILU-UV
      measurements, yielding a correlation of only 0.8025 and a mean relative
      difference of 28.25%. 

PMID- 25968370
TI  - Single-mode fiber variable optical attenuator based on a ferrofluid shutter.
AB  - We report on the fabrication and characterization of a single-mode fiber variable
      optical attenuator (VOA) based on a ferrofluid shutter actuated by a magnetic
      field created by a low voltage electromagnet. We compare the performance of a VOA
      using oil-based ferrofluid, with one VOA using water-based 12 ferrofluid, and
      demonstrate broadband optical attenuation of up to 28 dB with polarization
      dependent 13 loss of 0.85 dB. Our optofluidic VOA has advantages over MEMS-based
      VOAs such as simple construction and the absence of mechanical moving parts.

PMID- 25968371
TI  - Investigation of high-power diode-end-pumped Tm:YLF laser in slab geometry.
AB  - Comparative investigations of high-power diode-end-pumped Tm:YLF laser with a-cut
      and c-cut slab crystals were demonstrated. A maximum output power of 87.5 W of
      1907.8 nm Tm:YLF laser with two slab crystals was achieved, corresponding to a
      slope efficiency of 35.9% and an optical-to-optical efficiency of 32.1% with
      respect to the pump power. The c-cut slab Tm:YLF laser operated at 1907.8 nm with
      a beam quality factor of M<sup>2</sup>~1.79 at the output power level of 71.0 W.

PMID- 25968372
TI  - Novel analytical solution for the radiance in an anisotropically scattering
      medium.
AB  - We report on a novel analytical solution of the three-dimensional radiative
      transport equation for the case of an infinitely extended anisotropically
      scattering medium that is illuminated by an isotropic point light source. The
      resulting expression for the radiance can be evaluated efficiently and accurately
      and exhibits significant improvements with respect to the convergence and the
      numerical stability compared to the solutions found in the literature so far. The
      equations obtained were successfully verified by comparisons with the Monte Carlo
      method. 

PMID- 25968373
TI  - Highly efficient end-side-pumped Nd:YAG solar laser by a heliostat-parabolic
      mirror system.
AB  - We report a large improvement in the collection and slope efficiency of an Nd:YAG
      solar laser pumped by a heliostat-parabolic mirror system. A conical fused silica
      lens was used to further concentrate the solar radiation from the focal zone of a
      2 m diameter primary concentrator to a Nd:YAG single-crystal rod within a conical
      pump cavity, which enabled multipass pumping to the active medium. A 56 W cw
      laser power was measured, corresponding to 21.1  W/m2 record-high solar laser
      collection efficiency with the heliostat-parabolic mirror system. 4.9% slope
      efficiency was calculated, corresponding to 175% enhancement over our previous
      result.

PMID- 25968374
TI  - Using Doppler shift induced by Galvanometric mirror scanning to reach shot noise
      limit with laser optical feedback imaging setup.
AB  - This paper proposes what we believe is a new method to remove the contribution of
      parasitic reflections in the images of the laser optical feedback imaging (LOFI)
      technique. This simple method allows us to extend the LOFI technique to long
      distance applications, as imaging through a fog or a smoke. The LOFI technique is
      an ultrasensitive imaging technique that is interesting for imaging objects
      through a scattering medium. However, the LOFI sensitivity can be dramatically
      limited by parasitic optical feedback occurring in the experimental setup. In
      previous papers [Appl. Opt.48, 64 (2009)10.1364/AO.48.000064APOPAI1559-128X, Opt.
      Lett.37, 2514 (2012)10.1364/OL.37.002514OPLEDP0146-9592], we already have
      proposed methods to filter a parasitic optical feedback, but they are not well
      suited to metric working distances. This new method uses a Doppler frequency
      shift induced by the moving mirror used to scan the object to be imaged. Using
      this Doppler frequency shift, we can distinguish the photons reflected by the
      target and the parasitic photons reflected by the optical components in the
      experimental setup. In this paper, we demonstrated theoretically and
      experimentally the possibility to filter the parasitic reflection in LOFI images
      using the Doppler frequency shift. This method significantly improves the signal
      to-noise ratio by a factor 15 and we can obtain a shot noise limited image
      through a scattering medium of an object at 3 m from the detector.

PMID- 25968375
TI  - On-orbit calibration of the Suomi National Polar-Orbiting Partnership Visible
      Infrared Imaging Radiometer Suite for ocean color applications.
AB  - The NASA Ocean Biology Processing Group (OBPG) developed two independent
      calibrations of the Suomi National Polar-Orbiting Partnership (SNPP) Visible
      Infrared Imaging Radiometer Suite (VIIRS) moderate resolution reflective solar
      bands using solar diffuser measurements and lunar observations, and implemented a
      combined solar- and lunar-based calibration to track temporal changes in
      radiometric response of the instrument. Differences between the solar and lunar
      data sets have been used to identify issues and verify improvements in each.
      Linearization of the counts-to-radiance conversion yields a more consistent
      calibration at low radiance levels. Correction of a recently identified error in
      the VIIRS solar unit vector coordinate frame has been incorporated into the solar
      data and diffuser screen transmission functions. Temporal trends in the solar
      diffuser stability monitor data have been evaluated and addressed. Fits to the
      solar calibration time series show mean residuals per band of 0.067%-0.17%.
      Periodic residuals in the VIIRS lunar data are confirmed to arise from a
      wavelength-dependent libration effect for the sub-spacecraft point in the output
      of the U.S. Geological Survey Robotic Lunar Observatory photometric model of the
      Moon. Temporal variations in the relative spectral responses for each band have
      been assessed, and significant impact on band M1 (412 nm) lunar data has been
      identified and rectified. Fits to the lunar calibration time series,
      incorporating sub-spacecraft point libration corrections, show mean residuals per
      band of 0.069%-0.20%. Lunar calibrations have been used to adjust the solar
      derived radiometric corrections for bands M1, M3, and M4. After all corrections,
      the relative differences in the solar and lunar calibrations for bands M1-M7 are
      0.093%-0.22%. The OBPG has achieved a radiometric stability for the VIIRS on
      orbit calibration that is commensurate with those achieved for SeaWiFS and Aqua
      MODIS, supporting the incorporation of VIIRS data into the long-term NASA ocean
      color data record.

PMID- 25968376
TI  - Widely tunable LP11 cladding-mode resonance in a twisted mechanically induced
      long-period fiber grating.
AB  - A record tunability of 35 nm for the LP(11) cladding-mode resonance in a twisted
      mechanically induced long-period fiber grating using standard single-mode
      communication fiber is demonstrated. By forming the LP(11) resonance far away
      from its cut-off wavelength and modifying the grooves of the grating in the form
      of smooth semicircular humps, a high twist sensitivity of 8.75 nm/(rad/cm) and a
      controlled tunability of 35 nm is achieved. The fiber with its lacquer coating is
      not broken even at a severe twist rate of 5.44 rad/cm. The present design can be
      used as a novel variable optical selective wavelength attenuator since the
      bandwidth, rejection efficiency, and center wavelength can be controlled by
      changing the grating length, pressure over the grating, and fiber twist,
      respectively. Using the results, a cost-effective tunable variable optical
      attenuator for selective channel-blanking applications is also demonstrated. A
      fine tunability of 1.5 nm is achieved for a twist rate change of 0.1 rad/cm.

PMID- 25968377
TI  - Determination of the smoke-plume heights and their dynamics with ground-based
      scanning lidar.
AB  - Lidar-data processing techniques are analyzed, which allow determining smoke
      plume heights and their dynamics and can be helpful for the improvement of smoke
      dispersion and air quality models. The data processing algorithms considered in
      the paper are based on the analysis of two alternative characteristics related to
      the smoke dispersion process: the regularized intercept function, extracted
      directly from the recorded lidar signal, and the square-range corrected
      backscatter signal, obtained after determining and subtracting the constant
      offset in the recorded signal. The analysis is performed using experimental data
      of the scanning lidar obtained in the area of prescribed fires. 

PMID- 25968378
TI  - Theoretical and experimental study of suppressing stimulated Brillouin scattering
      and phase noise in interferometric fiber sensing systems with phase modulation.
AB  - The effect of phase modulation on the phase noise in remote interferometric fiber
      sensing systems is analyzed in both theory and experiment. A matching condition
      between the modulation frequency and optical delay difference is derived to
      choose the matching modulation frequency. The matching modulation frequency for
      an interferometer with 5 m optical-path difference is 60 MHz and its integer
      harmonic frequencies. By matching the condition, the phase modulation method can
      suppress the stimulated Brillouin scattering in an interferometric fiber sensing
      system effectively without bringing excess phase noise, which is verified by the
      experiment. The results indicate that the maximum input power of the system can
      be increased effectively, which has great potential in the design of remote
      interferometric fiber-sensing systems.

PMID- 25968379
TI  - Optical beam distortions induced by a shock wave.
AB  - The mean intensity and the displacement from the initially given propagation
      direction of the optical beam passed through the shock wave have been calculated.
      It has been shown that the spatial inhomogeneity of the refractive index of air
      caused by the shock wave arising in supersonic flow flowing a conical body can
      cause the focusing of the beam and strong anisotropic distortions of the
      intensity distribution in its cross section. The angular displacement of the
      optical beam from the initially given propagation direction owing to the shock
      wave depends only on the height above the Earth's surface at which the shock wave
      is formed. As the height increases, the influence of the shock wave on the
      optical beam propagating through it decreases. 

PMID- 25968380
TI  - Demodulation algorithm used in single-beam system immune to light power drift.
AB  - A demodulation algorithm based on the head-tail technique is proposed for single
      beam water vapor detection under rough environmental conditions, which is immune
      to fluctuations of light power. In the head-tail technique, collected data are
      processed by adding the head and tail data together and gradually approaching the
      center. The majority of photocurrent attenuation caused by optical loss can be
      effectively compensated by combining an optical intensity normalization
      coefficient in the method. The experiment indicates that, when the light power
      attenuates 4%, the deviation in a single-beam system is 1.29%, which is obviously
      superior to a dual-beam subtraction system whose deviation is 8.45%. The
      connection and advantages compared to a previous single-beam detection system
      have been discussed. The whole arrangement is simply designed without a beam
      splitter, of which the reliability and validity are fully verified by the
      experimental results. 

PMID- 25968381
TI  - Anisotropic non-Kolmogorov turbulence phase screens with variable orientation.
AB  - We describe a modification to fast Fourier transform (FFT)-based, subharmonic,
      phase screen generation techniques that accounts for non-Kolmogorov and
      anisotropic turbulence. Our model also allows for the angle of anisotropy to vary
      in the plane orthogonal to the direction of propagation. In addition, turbulence
      strength in our model is specified via a characteristic length equivalent to the
      Fried parameter in isotropic, Kolmogorov turbulence. Incorporating this feature
      enables comparison between propagating scenarios with differing anisotropies and
      power-law exponents to the standard Kolmogorov, isotropic model. We show that the
      accuracy of this technique is comparable to other FFT-based subharmonic methods
      up to three-dimensional spectral power-law exponents around 3.9. 

PMID- 25968382
TI  - Phase topography-based characterization of thermal effects on materials and
      joining techniques.
AB  - There are growing demands to characterize the stability of assemblies of optical
      components for ultrahigh-precision instruments. In this paper we demonstrate how
      absolute length measurements by interferometry can be applied to measure the
      thermal and dimensional stability of connections. In order to enable
      investigation of common joining techniques, including wringing, screwing, and
      gluing, as well as specialized, inorganic joining techniques such as silicatic
      bonding, thin-film soldering, and solderjet bumping, representative connections
      were fabricated. By using gage blocks or prismatic bodies as joining parts,
      parallelism and flatness were provided which are needed for precision
      interferometric length measurements. The stability of connection elements used in
      ultrahigh-precision instruments was investigated longitudinally and laterally to
      the connection interface, and also mutual tilting of the parts was detected by
      analysis of the phase topographies. The measurements have an accuracy level of
      about 1 nm, and the traditional wringing method was also considered as a
      reference joining technique. The long-term behavior was studied within a period
      of about 1 year under constant temperature. Further, the thermal dilatation and
      the reaction of connections to thermal stress were measured. Results show that
      screwed connections do not exhibit a significant drift of length or orientation.
      They also did not show response to temperature variations of +/-10 degrees C.
      This is different for adhesive connections, where dimensional changes of up to
      100 nm were observed. The specimens produced by using thin-film soldering as well
      as silicatic bonding revealed stability of length better than 5 nm per year and
      angular stability within +/-0.1   arcsec. Furthermore, these specimens were shown
      to be insensitive to a temporary temperature variation in a range from 10 degrees
      C to 40 degrees C. This situation is slightly different for the sample
      connections produced by solderjet bumping, which show a positive length change of
      ~25  nm and a tilt of ~1  arcsec. These observations can be explained by creeping
      of the relatively large solder bumps that bridge a gap of about 100 MUm between
      the connected mirror plates. The thermal expansion of the connections shows a
      strong correlation with the "layer thickness."

PMID- 25968383
TI  - Features for instantaneous emissions of low-level infrared signals of glucokinase
      enzyme from Pyrococcus furiosus.
AB  - A noncontact infrared (IR) imaging-based methodology and signal recovery tools
      are applied on an enzyme reaction as a test target. The method is implemented by
      a long-wave (8-12 MUm) IR microbolometer imaging array and a germanium-based IR
      optical vision. The reaction is carried out by the glucokinase, which produces a
      rapid exothermal release of energy that is weak, and, even worse, the IR video
      captured by the uncooled microbolometer detector is affected by spatial and
      temporal noise with specific complexities. Hitherto, IR-based signal recovery
      tools have worked with a standard acquisition frequency, which is clearly beyond
      the time scale of a real scenario. The implications of this (and similar) rapid
      reactions motivate the designs of a signal recovery method using prior
      information of the processes to extract and quantify the spontaneity of the
      enzymatic reaction in a three-dimensional (space and time) single and noncontact
      online measurement.

PMID- 25968384
TI  - Comparison of actively Q-switched laser performance of disordered Yb:Ca3La2(BO3)4
      crystals cut along the crystallographic axes.
AB  - In this paper, actively Q-switched laser operation with an acousto-optic switch
      has been demonstrated by using Yb:Ca3La2(BO3)4 crystals cut along the a, b, and c
      crystallographic axes. The most efficient Q-switched laser operation was obtained
      by using b-cut Yb:Ca3La2(BO3)4 crystal with 1 kHz pulse repetition frequency,
      generating laser pulses of 0.5 mJ, 42.56 KW peak power and 9 ns pulse width, when
      the output couplings were 3%, 5%, and 5%, respectively. Pulse performances and
      output laser spectra of the a-, b-, and c-cut Yb:Ca3La2(BO3)4 crystals were
      compared under similar experimental conditions.

PMID- 25968385
TI  - Midinfrared supercontinuum generation via As2Se3 chalcogenide photonic crystal
      fibers.
AB  - Using numerical analysis, we compare the results of optofluidic and rod filling
      techniques for the broadening of supercontinuum spectra generated by As2Se3
      chalcogenide photonic crystal fibers (PCFs). The numerical results show that when
      air-holes constituting the innermost ring in a PCF made of As2Se3-based
      chalcogenide glass are filled with rods of As2Se3-based chalcogenide glass, over
      a wide range of mid-IR wavelengths, an ultra-flattened near-zero dispersion can
      be obtained, while the total loss is negligible and the PCF nonlinearity is very
      high. The simulations also show that when a 50 fs input optical pulse of 10 kW
      peak power and center wavelength of 4.6 MUm is launched into a 50 mm long rod
      filled chalcogenide PCF, a ripple-free spectral broadening as wide as 3.86 MUm
      can be obtained.

PMID- 25968386
TI  - Vacuum ultraviolet spectropolarimeter design for precise polarization
      measurements.
AB  - Precise polarization measurements in the vacuum ultraviolet (VUV) region provide
      a new means for inferring weak magnetic fields in the upper atmosphere of the Sun
      and stars. We propose a VUV spectropolarimeter design ideally suited for this
      purpose. This design is proposed and adopted for the NASA-JAXA chromospheric
      lyman-alpha spectropolarimeter (CLASP), which will record the linear polarization
      (Stokes Q and U) of the hydrogen Lyman-alpha line (121.567 nm) profile. The
      expected degree of polarization is on the order of 0.1%. Our spectropolarimeter
      has two optically symmetric channels to simultaneously measure orthogonal linear
      polarization states with a single concave diffraction grating that serves both as
      the spectral dispersion element and beam splitter. This design has a minimal
      number of reflective components with a high VUV throughput. Consequently, these
      design features allow us to minimize the polarization errors caused by possible
      time variation of the VUV flux during the polarization modulation and by
      statistical photon noise. 

PMID- 25968387
TI  - 3 * 3 coupler based interferometric magnetic field sensor using a TbDyFe rod.
AB  - An all-fiber magnetic field sensor by using a TbDyFe rod as the sensing element
      for the measurement of the weak alternating magnetic field is presented and
      experimentally demonstrated. The sensor is constructed with a 3*3 coupler based
      Mach-Zehnder interferometer, and the time-varying phase shift induced by the
      applied magnetic field is recovered by using a passive demodulation method. The
      experimental results show that the sensor exhibits excellent linearity and
      reversibility within 0-75 MUT (residual mean square), and a high sensitivity of
      69.83 mrad/MUT (residual mean square) with a resolution of 2.14  nT/?Hz (residual
      mean square) at 200 Hz is experimentally achieved. The frequency response and the
      temperature characteristic of the sensor are also investigated.

PMID- 25968388
TI  - Design of three-mirror illumination system with free-form fly's eye for extreme
      ultraviolet lithography.
AB  - The low source power is one of the major challenges that hinder the extreme
      ultraviolet lithography from high volume manufacturing. To alleviate the source
      development pressure, a high-efficiency illumination system with three mirrors is
      proposed, based on the authors' knowledge, for the first time. Free-form fly's
      eye is introduced into the system to get a qualified arc-shaped irradiance
      distribution on the reticle. A method integrated with a numerical method and
      optimization to design the free-form surface is given in detail. The transfer
      efficiency of the system is much higher than that of the four-mirror
      configuration employed in the EUV exposure platform. Compared with the previous
      high-efficiency illumination system with two mirrors, this configuration can
      ensure a good uniformity and will not increase the objective design difficulty or
      affect the image quality of the objective. Simulation result of the design with
      three mirrors shows the uniformity on the reticle is about 95.5%, and the energy
      efficiency is about 25.4%. It indicates that the system is effective in enhancing
      the efficiency and potential to promote the EUV lithography into high volume
      manufacturing. 

PMID- 25968389
TI  - Silicon-based dual ARROW power splitters with remote coupling.
AB  - In this research, Si-based power splitters based on dual antiresonant reflecting
      optical waveguides (ARROW) with remote coupling by a separation distance of 30
      MUm were designed and realized. Characterization of the power splitters with
      different lengths of the coupling region was performed. Measurement
      characteristics of fabricated devices with the propagation losses lower than 1.90
      dB/cm and the imbalances lower than 0.60 dB show that our dual ARROW power
      splitters can be efficiently realized.

PMID- 25968390
TI  - Precise measurement of three-dimensional positions of transparent ellipsoidal
      particles using digital holographic microscopy.
AB  - The dynamic motions of various particles suspended in microscale flows are
      essential phenomena in the scientific and engineering fields. These motions can
      be precisely measured by using 3D quantitative flow visualization techniques.
      Moreover, most cells and particles in nature possess a nonspherical shape.
      Digital holographic microscopy (DHM) is employed to measure the 3D positional
      information of transparent ellipsoidal particles. Both in-plane and out-of-plane
      positional information are obtained by analyzing the distinctive light scattering
      from the microsized ellipsoidal particles. The performance of the 3D position
      measurement method is experimentally verified for ellipsoidal particles seeded in
      a planar surface and a microtube. This DHM technique exhibits promising potential
      in the dynamic analysis of ellipsoidal particles and cells suspended in various
      microscale fluid flows. 

PMID- 25968391
TI  - Direct measurement of the parameters of a femtosecond pulse train with a THz
      repetition rate generated by the interference of two phase-modulated femtosecond
      pulses.
AB  - A femtosecond pulse train with THz repetition rate generated by the interference
      of two phase-modulated pulses has been recorded experimentally. Pulse repetition
      rates and their duration have been measured. It has been shown that at the 50-fs
      time delay between phase-modulated pulses the repetition rate is 3.1 THz with a
      pulse width of 200 fs, while at the 120-fs time delay the repetition rate is 7.1
      THz with a pulse width of 67 fs.

PMID- 25968392
TI  - High-power passively mode-locked laser at 1062.4  nm based on Nd:LaGGG disordered
      crystal.
AB  - A diode-pumped passively continuous-wave mode-locked Nd:(La(x)Gd(1-x))3Ga5O12
      (Nd:LaGGG) laser at 1062.4 nm with a semiconductor saturable absorber mirror was
      demonstrated for the first time, to the best of our knowledge. Pulses with
      duration of 12.78 ps were produced at a repetition rate of 59.8 MHz. A maximum
      average mode-locked output power of 3.18 W was obtained at the absorbed pumped
      power of 10.12 W, corresponding to a slope efficiency of 35.7% and a peak power
      of 4.2 kW. As far as we know, this is the highest power obtained in the passively
      mode-locking operation with Nd3+-doped disordered garnet crystals.

PMID- 25968393
TI  - Detection of carcinogenic metals in kidney stones using ultraviolet laser-induced
      breakdown spectroscopy.
AB  - The UV single-pulsed (SP) laser-induced breakdown spectroscopy (LIBS) system was
      developed to detect the carcinogenic metals in human kidney stones extracted
      through the surgical operation. A neodymium yttrium aluminium garnet laser
      operating at 266 nm wavelength and 20 Hz repetition rate along with a
      spectrometer interfaced with an intensified CCD (ICCD) was applied for spectral
      analysis of kidney stones. The ICCD camera shutter was synchronized with the
      laser-trigger pulse and the effect of laser energy and delay time on LIBS signal
      intensity was investigated. The experimental parameters were optimized to obtain
      the LIBS plasma in local thermodynamic equilibrium. Laser energy was varied from
      25 to 50 mJ in order to enhance the LIBS signal intensity and attain the best
      signal to noise ratio. The parametric dependence studies were important to
      improve the limit of detection of trace amounts of toxic elements present inside
      stones. The carcinogenic metals detected in kidney stones were chromium, cadmium,
      lead, zinc, phosphate, and vanadium. The results achieved from LIBS system were
      also compared with the inductively coupled plasma-mass spectrometry analysis and
      the concentration detected with both techniques was in very good agreement. The
      plasma parameters (electron temperature and density) for SP-LIBS system were also
      studied and their dependence on incident laser energy and delay time was
      investigated as well.

PMID- 25968394
TI  - Amplitude and phase retrieval in simultaneous pi/2 phase-shifting heterodyne
      interferometry using the synchrosqueezing transform.
AB  - This paper presents a method for amplitude and phase retrieval in simultaneous
      pi/2 phase-shifting heterodyne interferometry. The used optical setup admits the
      introduction of a temporal carrier and simultaneously verifies the two-beam
      interferometry equation for each intensity signal, which are pi/2  rad out of
      phase (quadrature). The spatiotemporal recovering process is obtained by
      isolating the object amplitude and phase using wavelet transform analysis of the
      temporal series composed by the difference between the measured pixel intensities
      corresponding to each quadrature signal. This process is subsequently improved by
      introducing a framework based on the synchrosqueezing transform, which recovers
      the data of interest with higher accuracy when very low scattering amplitudes and
      phase excursions must be determined in noisy working conditions. The advantages
      and limitations of the presented method are analyzed and discussed using
      numerical simulations and also experimental data obtained from temporal speckle
      pattern interferometry.

PMID- 25968395
TI  - Photoinduced insulator-to-metal transition and surface statistics of VO2
      monitored by elastic light scattering.
AB  - Measurements of ultrafast light scattering within a hemisphere are performed for
      statistical analysis of nonequilibrium processes in VO2 epitaxial film. A
      Gerchberg-Saxton error reduction algorithm is applied for accurate calculation of
      a surface autocorrelation function from light scattering data and for partial
      reconstruction of a power spectral density function. Upon ultrafast photoinduced
      phase transition of VO2, the elastic light scattering reveals anisotropic grain
      size-dependent dynamics. It was found that the transition rate depends on the
      optical absorption and orientation of VO2 grains with respect to polarization of
      the pump pulse. An observed stepwise evolution of surface autocorrelation length
      and transient anisotropy of the scattering field presumably originates from
      complex multistage transformation of VO2 lattice on a subpicosecond time scale.

PMID- 25968396
TI  - Long-range surface plasmons supported by a bilayer metallic structure for sensing
      applications.
AB  - We show, both theoretically and experimentally, that long-range surface plasmons
      (LRSPs) are supported by asymmetric structure, consisting of a thin silver/gold
      bilayer metallic film sandwiched between a magnesium fluoride (i.e.,
      MgF<sub>2</sub>) buffer layer and a sensing medium (water). The geometrical
      parameters of the structure are optimized to yield efficient excitation of LRSPs
      by using transfer matrix method based on Fresnel reflection. The excitation of
      LRSPs was performed by using a custom-made automated optical setup based on
      angular interrogation with the precision of 0.01 degrees . We demonstrate that
      the bimetallic asymmetric structure achieves better minimum reflectivity
      resolution than monometallic (gold) asymmetric structure. Finally, figures of
      merit are compared for bimetallic, monometallic, and conventional SPR structures,
      and we found that the bimetallic asymmetric structure provides a higher figure of
      merit; e.g., more than double for monometallic LRSP configuration and 8 times as
      compared to the conventional surface plasmon resonance sensor. 

PMID- 25968397
TI  - Semi-analytical model of arrayed waveguide grating in SOI using Gaussian beam
      approximation.
AB  - The arrayed waveguide grating structure can be used as an important component in
      high-speed CMOS optical interconnects in silicon-on-insulator (SOI) platform.
      However, the performance of such device is found to be extremely sensitive to the
      fabrication-related errors in defining the critical features. In the absence of
      an appropriate analytical model, one needs to rely on numerical computation to
      analyze the device characteristics and fabrication tolerances. Because compact
      design of such a device structure has foot-print ~mm<sup>2</sup> and the smallest
      features can be as small as ~500  nm*220  nm (waveguide cross section), it
      demands a huge computational budget to optimize the design parameters. A semi
      analytical model using Gaussian beam approximation of guided mode profiles has
      been developed to analyze the output spectrum of arrayed waveguide grating and to
      estimate the phase errors due to waveguide inhomogeneities. This model has been
      validated with existing numerical methods and published experimental results. It
      has been observed that a probabilistic waveguide width variations of DeltaW~5  nm
      can cause a cross-talk degradation of about 40 dB (25 dB) for a device (operating
      at lambda~1550  nm) fabricated on SOI substrate with 220 nm (2 MUm) device layer
      thickness.

PMID- 25968398
TI  - Pitfalls and possibilities of radar compressive sensing.
AB  - In this paper, we consider the application of compressive sensing (CS) to radar
      remote sensing applications. We survey a suite of practical system-level issues
      related to the compression of radar measurements, and we advocate the
      consideration of these issues by researchers exploring potential gains of CS in
      radar applications. We also give abbreviated examples of decades-old radio
      frequency (RF) practices that already embody elements of CS for relevant
      applications. In addition to the cautionary implications of system-level issues
      and historical precedents, we identify several promising results that RF
      practitioners may gain from the recent explosion of CS literature. 

PMID- 25968399
TI  - Compressive sensing in the EO/IR.
AB  - We investigate the utility of compressive sensing (CS) to electro-optic and
      infrared (EO/IR) applications. We introduce the field through a discussion of
      historical antecedents and the development of the modern CS framework. Basic
      economic arguments (in the broadest sense) are presented regarding the
      applicability of CS to the EO/IR and used to draw conclusions regarding
      application areas where CS would be most viable. A number of experimental success
      stories are presented to demonstrate the overall feasibility of the approaches,
      and we conclude with a discussion of open challenges to practical adoption of CS
      methods. 

PMID- 25968401
TI  - Compressive Sensing Focus Issue: introduction.

PMID- 25968400
TI  - Compressive sensing in medical imaging.
AB  - The promise of compressive sensing, exploitation of compressibility to achieve
      high quality image reconstructions with less data, has attracted a great deal of
      attention in the medical imaging community. At the Compressed Sensing Incubator
      meeting held in April 2014 at OSA Headquarters in Washington, DC, presentations
      were given summarizing some of the research efforts ongoing in compressive
      sensing for x-ray computed tomography and magnetic resonance imaging systems.
      This article provides an expanded version of these presentations. Sparsity
      exploiting reconstruction algorithms that have gained popularity in the medical
      imaging community are studied, and examples of clinical applications that could
      benefit from compressive sensing ideas are provided. The current and potential
      future impact of compressive sensing on the medical imaging field is discussed. 

PMID- 25968402
TI  - International Year of Light: editorial.

PMID- 25968403
TI  - Effects of Renal Denervation from the Intima and the Adventitia of Renal Arteries
      on Renal Sympathetic Nerve Activity in Dogs: A Comparative Study.
AB  - OBJECTIVES: This study was designed to observe the efficacy and safety of renal
      denervation from the inside and outside of renal arteries. METHODS: Fourteen
      beagles were randomly divided into a control group (n = 4) and treatment group (n
      = 10). One renal artery in every beagle of the treatment group was randomly
      assigned to an intimal group (10 renal arteries) which underwent percutaneous
      renal denervation from the inside, and another renal artery was assigned to an
      adventitial group (10 renal arteries) which underwent renal denervation from the
      outside by laparotomy. RESULTS: Compared with the intimal group, the renal
      norepinephrine (NE) concentration in the adventitial group had significantly
      decreased (p = 0.003) at 3 months postsurgery. Renal artery HE staining showed
      that the perineurium from the adventitial group appeared thickened. Western
      blotting showed that renal tissue tyrosine hydroxylase (TH) protein expression in
      the adventitial group was significantly lower than that in the intimal group (p <
      0.01) at 3 months postsurgery. There was a renal artery stenosis and a renal
      atrophy in the intimal group after 1 month of follow-up. CONCLUSION: The
      inhibitory effect on renal sympathetic nerve activity was more effective in the
      adventitial group than the intimal group, and renal denervation in the former
      group was safe.

PMID- 25968404
TI  - The fluid dynamics of simultaneous irrigation with negative pressure wound
      therapy.
AB  - Saline irrigation has been shown to be both experimentally and clinically
      efficacious in decreasing bacterial contamination as well as decreasing infection
      rates. The dynamics of irrigation delivery fall into two primary categories:
      simultaneous and intermittent irrigation. An important component to irrigation
      therapy is distribution of irrigation solution to hard-to-reach areas of a wound
      bed, including undermining and fissure-like structures. Here we test the
      effectiveness of simultaneous irrigation to fill the irregular structures of a
      wound bed. In order to visualise the dynamic movement of irrigation solution,
      three-dimensional wound models were constructed using clear synthetic ballistic
      gel. Wounds with the aforementioned characteristics were carved into the
      ballistic gel with varying area, depth and volume. All three wounds were dressed
      as per manufacturer's instructions. Data demonstrate that simultaneous irrigation
      is effective in reaching all parts of a wound bed in wound models that have both
      undermining and tunnelling, and irrigation effectively saturates bridged wounds.
      Finally, this study shows that there is constant turnover of irrigation solution
      in the wound that is driven more by administration volume and less by flow rate.
      These data show that simultaneous irrigation is an effective technique for
      delivering irrigation solution to both simple and complex wounds. 

PMID- 25968405
TI  - Common sources of disparate results and experience in clinical practice vs.
      results from phase 2 registration studies: lamotrigine as a prototype.

PMID- 25968406
TI  - Daily dietary intakes of zinc, copper, lead, and cadmium as determined by
      duplicate portion sampling combined with either instrumental analysis or the use
      of food composition tables, Shiraz, Iran.
AB  - Estimation of essential and toxic element intakes is crucial to evaluate the
      risks of deficiency or toxicity. The purpose of this study was to investigate and
      also to compare the dietary intakes of zinc (Zn) and copper (Cu) by adults living
      in Shiraz, Iran, determined by two procedures: duplicate portion sampling of 21
      hospital meals combined with either instrumental analysis (voltammetric
      measurement) or the use of food composition tables (FCTs). The level of exposure
      to lead (Pb) and cadmium (Cd) was evaluated as well. The daily Zn intakes of both
      methods were not significantly different and were higher than the RDA values
      except the value measured by the instrumental analysis which was lower than the
      RDA established for a male adult. Daily intake of Cu determined by instrumental
      analysis was significantly lower and closer to RDA for adults compared with the
      value estimated by FCTs. The dietary intakes of Pb and Cd were 313 and 61% of the
      respective provisional tolerable weekly intakes (PTWIs), respectively. The
      accuracy of two methods used for estimation of Zn intake was similar. In the case
      of Cu, the use of FCTs, in which the influence of environmental conditions and
      dietary habits of meal preparation is not taken into account, overestimated
      dietary intake. The risk of zinc deficiency was found in adult males. Moreover,
      the estimated intake of Pb, but not Cd, could be a cause of concern for Shiraz
      population. Thus, conducting regular periodic studies to assess the dietary
      intake of mentioned elements are recommended.

PMID- 25968407
TI  - Effect of preoperative oral pravastatin reload in systemic inflammatory response
      and myocardial damage after coronary artery bypass grafting. A pilot double-blind
      placebo-controlled study.
AB  - AIM: Statins exert pleiotropic effects that result in cardioprotective and
      antiinflammatory properties. There is a lack of information about the effect of
      preoperative reloading statin administration in surgical coronary patients
      regarding myocardial protection, systemic inflammatory response (SIR) attenuation
      and nitric oxide (NO) metabolism. METHODS: Thirty consecutive dyslipidemic
      patients under chronic treatment with statins were randomized to orally receive
      pravastatin 80 mg (N.=10), 40 mg (N.=10) or placebo (N.=10) two hours before
      anesthetic induction for non-emergent on-pump coronary artery bypass grafting
      (CABG) procedures. Perioperative peripheral venous and intraoperative CS blood
      samples were collected for determination of drug-related adverse effects, NO
      metabolism and both myocardial damage and SIR biomarkers. RESULTS: Pravastatin
      reloading resulted in a significant and dose-related intense attenuation of SIR,
      but no differences in cardiac damage biomarker levels were demonstrated. NO
      release and inducible nitric oxide synthase expression was significantly reduced
      in both treatment groups. Highest pravastatin doses significantly increased
      systemic creatine phosphokinase (CPK) concentration compared with intermediate
      doses but no other adverse effects were observed. CONCLUSION: Oral pravastatin
      reloading before non-emergent CABG significantly attenuates postoperative SIR and
      systemic NO/iNOS concentrations with no effect in perioperative myocardial
      damage. Highest pravastatin doses increase CPK levels and must be avoided in
      susceptible patients.

PMID- 25968408
TI  - Coronary artery bypass graft surgery in patients with left ventricular
      dysfunction.
AB  - AIM: The aim of this study was to investigate effects of congestive heart failure
      on coronary revascularization results in patients with left ventricular
      dysfunction and operated for elective coronary revascularization. METHODS: The
      data were collected retrospectively from 126 consecutive patients with left
      ventricular dysfunction caused by coronary artery disease between January 2007
      and January 2012. Patients admitted to hospital with angina complaints without
      congestive heart failure symptoms were group 1 and patients with severe
      congestive heart failure symptoms were group 2. Accompanying diseases,
      postoperative complications and mortality were recorded. RESULTS: There were 66
      patients in group 1 and 60 patients in group 2. Postoperative maximal inotropic
      support was necessary in 24 (36.4%) patients in group 1 for a mean duration of
      1.6+/-0.9 days and in 34 (56.7%) patients in group 2 for a mean duration of 2.9+/
      0.7 days. The proportion of patients with postoperative stay at the intensive
      care unit longer than 48 hours was significantly higher in group 2 compared to
      group 1. (p=0.0001) Hospital mortality was significantly higher in group 2
      compared to group 1. (p=0.0001) CONCLUSION: Congestive heart failure aggravates
      the outcome after coronary artery bypass surgery in patients with left
      ventricular dysfunction.

PMID- 25968409
TI  - Ni-Catalyzed Divergent Cyclization/Carboxylation of Unactivated Primary and
      Secondary Alkyl Halides with CO2.
AB  - A user-friendly Ni-catalyzed reductive cyclization/carboxylation of unactivated
      alkyl halides with CO2 is described. The protocol operates under mild conditions
      with an excellent chemoselectivity profile and a divergent syn/anti selectivity
      pattern that can be easily modulated by the substrate utilized. 

PMID- 25968411
TI  - [Evaluation of Treatment of Mothers at the Family Day Hospital in Munster,
      Germany].
AB  - Evaluation of Treatment of Mothers at the Family Day Hospital in Munster,
      Germany. Mothers of preschool children have limited access to mental health
      treatment services. The Family Day Hospital for Preschool Children at the
      University Hospital Munster, Germany, offers therefore a specialized treatment
      for mothers with their preschool children. The therapy outcome of mothers is
      evaluated in effectiveness study by a pre-post-design. For mothers, therapy was
      composed of individual session and couple sessions with the partner, video-based
      parent-child-interaction therapy, and parent group sessions. We evaluated the
      psychiatric symptom burden of N = 103 mothers at admission and discharge with the
      Symptom Checklist-90-Revised (SCL-90-R) above the clinical cut-off &#8805; 0.57.
      After treatment the mothers showed significant improvement on the global severity
      index (GSI) with an average Cohen's d = 1.64 (p0.001). We identified the
      following positively associated moderator variables of maternal improvement by a
      multiple regression analysis: the initial symptom burden, the educational level
      of the mother, not restricted housing conditions, and the age of the child. We
      conclude that especially distressed parents benefit from the treatment in the
      Family Day Hospital for Preschool Children. 

PMID- 25968412
TI  - [Psychological Symptom Burden in Children and Adolescents After Leukemia or
      Lymphoma Diseases].
AB  - Psychological Symptom Burden in Children and Adolescents After Leukemia or
      Lymphoma Diseases. A cancer diagnosis represents a major challenge for children
      and young people at an early stage in life. Objective of the present study is the
      investigation of mental health and psychosocial burden in children and young
      adolescents two or more years after the treatment of leukemia (ALL, AML) or
      lymphoma disease (NHL) compared to peers not suffering from cancer as well as
      available standard values. 42 former patients and 23 healthy peers were included
      in the comparative analysis. In addition to socio-demographic and medical
      information the following validated questionnaires were used: the General
      Depression Scale (ADS), the Strength and Difficulties Questionnaire (SDQ) for the
      detection of behavioral difficulties and strengths, the KINDL-R questionnaire for
      assessing quality of life in children and adolescents, the Herth Hope Index
      (HHI), the Social Questionnaire (SFS 4-6) for assessing the educational
      integration and the General Self-Efficacy Scale (GSE) to measure self-efficacy.
      Children and young adolescent survivors of leukemia or lymphoma report
      significantly less depressive symptoms and significantly higher quality of life
      compared to a healthy age-matched comparison sample and representative standard
      values. Beyond, former patients do not differ significantly in psychological and
      psychosocial aspects compared to a healthy age-matched comparison sample and
      available standard values. 

PMID- 25968413
TI  - [Gene-environment-interaction of ODD and Conduct Disorder Versus "Anethic
      Psychopathy"].
AB  - Gene-environment-interaction of ODD and Conduct Disorder Versus "Anethic
      Psychopathy". In 1934, Kramer and von der Leyen demonstrated in a sophisticated
      longitudinal study with eleven conduct disordered and neglected children labelled
      as "anethic psychopaths" that "anethic traits" subsided in a favourable
      educational setting. Sound prognoses, due to the diversity of environmental
      factors, were found to be impossible. On the contrary they stated that negative
      labelling led to an affirmation of a negative prognosis. In theory, they supposed
      a genetic predisposition resulting in a heightened sensitivity to the
      environment. This early theory of epigenetics radically contradicted the Nazi
      dogma of hereditability and ostracism and the selection procedures in mainstream
      psychiatry at that time. The debate ended with von der Leyen's suicide and the
      prohibition of medical work and publication towards Kramer. Even after the end of
      the Nazi policy of "eradication of the socially debased", this early theory was
      not taken on again, nor dignified. 

PMID- 25968415
TI  - [Test review].

PMID- 25968418
TI  - Unilateral Nipple Eczema in Children: Report of Five Cases and Literature Review.
AB  - Bilateral nipple eczema on the background of atopy is not an uncommon problem and
      is a minor criterion in some diagnostic systems for atopic dermatitis (AD), but
      unilateral atopic nipple eczema is underrecognized and often causes clinical
      concern. We present the first case series of children with unilateral atopic
      nipple eczema and discuss the clinical aspects of this unusual distribution.

PMID- 25968420
TI  - Narrative innovations predict symptom improvement: Studying innovative moments in
      narrative therapy of depression.
AB  - OBJECTIVE: Innovative moments (IMs) are moments in the therapeutic dialog that
      constitute exceptions toward the client's problems. These narrative markers of
      meaning transformation are associated with change in different models of therapy
      and diverse diagnoses. Our goal is to test if IMs precede symptoms change, or, on
      the contrary, are a mere consequence of symptomatic 15 change. METHOD: For this
      purpose, IMs and symptomatology (Outcome Questionnaire-10.2) were assessed at
      every session in a sample of 10 cases of narrative therapy for depression.
      Hierarchical linear modeling was conducted to explore whether (i) IMs in a given
      session predict patients' symptoms in the following session and/or (ii) symptoms
      in a given session predict IMs in the next session. RESULTS: Results suggested
      that IMs are better predictors of symptoms than the reverse. CONCLUSIONS: These
      results are discussed considering the contribution of meanings and narrative
      processes' changes to symptomatic improvement.

PMID- 25968421
TI  - Anti-Amoxicillin Immunoglobulin E, Histamine-2 Receptor Antagonist Therapy and
      Mast Cell Activation Syndrome Are Risk Factors for Amoxicillin Anaphylaxis.
AB  - BACKGROUND: beta-Lactam antibiotics (mainly amoxicillin, AX) are the drugs that
      most frequently induce systemic drug allergy reactions. OBJECTIVE: We attempted
      to identify the risk factors associated with systemic reactions to AX. METHODS:
      All patients who were referred to our department for suspected hypersensitivity
      reactions to AX over a 6-month period were evaluated for anti-AX immunoglobulin E
      (IgE) levels and skin-test positivity for beta-lactams. Age, sex, concomitant
      diseases, therapies, total IgE, serum tryptase levels and signs and symptoms
      suggesting mast cell activation syndrome (MCAS) were analyzed in relation to the
      severity of the reaction in accordance with the Mueller classification. RESULTS:
      Sixty-seven patients were selected: 39 with mild reactions such as cutaneous or
      gastrointestinal symptoms (grades I and II) and 28 with severe systemic reactions
      (grades III and IV). Anti-AX IgE levels and total IgE were significantly higher
      in severe reactions than in mild ones (p < 0.00005, p = 0.0037). Treatment with
      histamine-2 receptor antagonists (anti-H2) was significantly related to severe
      reactions (p = 0.007). No significant correlations were found between the
      severity of the reactions and dyslipidemia or levels of angiotensin-converting
      enzyme and tryptase. CONCLUSION: Anti-AX IgE levels were the most significant
      immunological parameter distinguishing patients who presented with severe
      reactions to AX and those with mild reactions. Higher values of total IgE, the
      use of gastroprotective drugs and signs and symptoms suggesting an MCAS
      significantly increased the odds ratio of having a severe reaction. The risk of
      serious adverse reactions to AX increased in older patients and in males, but
      this trend was not significant.

PMID- 25968419
TI  - Stored red blood cell susceptibility to in vitro transfusion-associated stress
      conditions is higher after longer storage and increased by storage in saline
      adenine-glucose-mannitol compared to AS-1.
AB  - BACKGROUND: Biochemical changes induced in red blood cells (RBCs) during storage
      may impair their function upon transfusion. Transfusion-associated stresses may
      further amplify storage lesion effects including increased phosphatidylserine
      (PS) exposure at the RBC membrane, microparticle (MP) release, and adhesion to
      endothelial cells (ECs). RBC stress susceptibility in vitro was investigated in
      relation to storage time and additive solution. STUDY DESIGN AND METHODS:
      Leukoreduced whole blood donations (n = 18) were paired, mixed, and resplit
      before separating the RBCs for storage in saline-adenine-glucose-mannitol (SAGM)
      or AS-1. Samples were taken after 3, 21, or 35 days. For oxidative stress
      treatment, RBCs were exposed to 0.5 mmol/L tert-butylhydroperoxide. Transfusion
      associated stress was simulated by overnight culture at 37  degrees C with plasma
      containing inflammatory mediators. PS exposure and MPs were measured by flow
      cytometry and adhesion to ECs was tested under flow conditions. PS specificity of
      adhesion was tested by blocking with PS-containing lipid vesicles. RESULTS:
      Oxidative stress induced significantly higher PS exposure and adhesion to ECs in
      RBCs stored for 35 days compared to 3 days (p < 0.04). PS-containing vesicles
      blocked RBC-EC adhesion. After overnight culture with or without plasma, PS
      exposure and EC adhesion were significantly increased (p < 0.05). MP numbers
      increased with longer RBC storage and after RBC culture with plasma. Culture
      conditions influenced MP numbers from Day 35 RBCs. RBCs stored in SAGM had
      significantly higher PS exposure after stress treatment than AS-1 RBCs (p <
      0.02). CONCLUSION: Storage for 35 days significantly increased RBC susceptibility
      to oxidative and in vitro transfusion-associated stresses and was higher for RBCs
      stored in SAGM compared to AS-1.

PMID- 25968422
TI  - From Chemical Gardens to Fuel Cells: Generation of Electrical Potential and
      Current Across Self-Assembling Iron Mineral Membranes.
AB  - We examine the electrochemical gradients that form across chemical garden
      membranes and investigate how self-assembling, out-of-equilibrium inorganic
      precipitates-mimicking in some ways those generated in far-from-equilibrium
      natural systems-can generate electrochemical energy. Measurements of electrical
      potential and current were made across membranes precipitated both by injection
      and solution interface methods in iron-sulfide and iron-hydroxide reaction
      systems. The battery-like nature of chemical gardens was demonstrated by linking
      multiple experiments in series which produced sufficient electrical energy to
      light an external light-emitting diode (LED). This work paves the way for
      determining relevant properties of geological precipitates that may have played a
      role in hydrothermal redox chemistry at the origin of life, and materials
      applications that utilize the electrochemical properties of self-organizing
      chemical systems. 

PMID- 25968427
TI  - Amniotic fluid LPCAT1 mRNA correlates with the lamellar body count.
AB  - Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is required in the
      biosynthesis of pulmonary surfactant. This short communication describes our
      assessment of LPCAT1 mRNA levels in human amniotic fluid. We found a direct
      correlation between LPCAT1 mRNA copies and the amniotic fluid lamellar body count
      (LBC). This finding corroborates an association between LPCAT1 and surfactant
      phospholipid biosynthesis in humans. It may provide a model for future research
      in perinatal medicine. 

PMID- 25968428
TI  - On the track to adulthood: the missions of the young human being, dodging the
      risks and gaining the tools.
AB  - Medical staff are expected to cooperate with other professions and agencies in
      helping the young human in achieving the goal of becoming a healthy, well-
      functioning adult that expresses her/his maximal potential. Achieving this goal
      should be cost-effective. Cost includes not just the economic burden but also
      psychosocial determinants such as emotional disruption, stress, living at risk,
      malfunctioning, and dependency. Acknowledging the risks and the expected
      achievements at each age are useful in analyzing the failure of community health
      programs and in planning preventive modalities and needed remedies. 

PMID- 25968429
TI  - Assessment and relation of total and regional fat mass with bone mineral content
      among Indian urban adolescents.
AB  - BACKGROUND: Fat mass (FM) has been shown to have an effect on bone mass accrual.
      Though gender and ethnic differences in body composition and bone accrual during
      puberty have been reported, there are limited data available for Indian children
      and adolescents. OBJECTIVE: To generate age and gender based percentile charts of
      FM among urban Indian children and adolescents and to evaluate the relationship
      with pubertal status and bone mineral content (BMC). SUBJECTS: There were 1403
      children and adolescents (boys: 826; girls: 577) in the study. METHODS: Total and
      regional FM, BMC, and pubertal staging were assessed. Fat mass index (FMI),
      FM/height ratio and BMC/FM ratio, were calculated. RESULTS: The age of the study
      population ranged from 5 to 18 years, with a mean age of 13.2 +/- 2.7 years
      (boys: 13.0 +/- 2.7; girls: 13.4 +/- 2.8 years). Total and regional FM as well as
      FMI increased with increasing age in both genders. The highest percent increase
      in mean total FM occurred in the age group > 8-11 years and decreased thereafter.
      The total and regional FM was higher in more advanced stages of pubertal
      maturation. There was no difference in total and regional FM between genders in
      prepubertal group. The age and pubertal associated increase in FM was
      significantly higher in girls than boys (p < 0.0001). Total as well as regional
      FM and FMI were positively correlated with age, body mass index, total lean mass,
      and BMC even after adjusting for age, lean mass, and biochemical parameters.
      CONCLUSIONS: Total and regional FM increased with age and pubertal maturation in
      both genders. FM was positively correlated with BMC.

PMID- 25968430
TI  - Carotid intimal medial thickness and its relation to endothelial dysfunction and
      echocardiographic changes in adolescents with type 1 diabetes.
AB  - AIM: To assess carotid intimal medial thickness (cIMT) in adolescent type 1
      diabetic patients and to detect its relation with echocardiographic changes and
      flow mediated dilatation (FMD) in the brachial artery. METHODS: The study
      included 62 type 1 diabetic patients and 30 healthy volunteer of the same age and
      sex. A blood sample was taken for analysis of glycosylated hemoglobin and lipid
      profile and a urine sample was taken for analysis of albumin/creatinine ratio.
      cIMT, echocardiography, and FMD via ultrasound were also done; t-test or Mann
      Whitney U-test (for non-symmetrically distributed data) for independent variables
      and Pearson's or Spearman correlation were used. RESULTS: The mean age of
      patients was 16.3 +/- 1.5 years and mean duration of diabetes was 9.4 +/- 2.9
      years. cIMT (Rt, Lt, and both Rt and Lt) were significantly higher, while FMD and
      FMD/nitrate mediated dilatation (NMD) ratio was significantly lower in diabetics.
      Rt cIMT had a significant negative correlation with FMD and FMD/NMD. cIMT had a
      significant positive correlation with left ventricular end diastolic dimension,
      inter ventricular septum thickness, peak mitral flow velocity during early
      diastole/peak mitral flow velocity during late diastole, left ventricular mass,
      and left ventricular mass index (p<0.05). In addition, cIMT had a significant
      correlation with waist circumference, waist/height ratio, albumin/ creatinine
      ratio, total cholesterol, and triglyceride. CONCLUSION: We conclude that
      alteration in myocardial function and vascular endothelial dysfunction induced by
      diabetes mellitus may begin early with the association of early atherosclerotic
      changes.

PMID- 25968431
TI  - Psychiatric disorders are associated with increased risk for developing
      hyponatraemia in children.

PMID- 25968432
TI  - Migratory polyarthritis as an adverse effect of thiamazole use in a 13-year-old
      girl with Graves' disease.
AB  - Graves' disease is the most prevalent cause of hyperthyroidism in children. The
      treatment commonly involves antithyroid therapy using a thionamide. We present a
      case of a 13-year-old girl with the antithyroid arthritis syndrome, presenting as
      a migratory polyarthritis, after the initiation of thionamide treatment for
      Graves' disease. Antithyroid arthritis syndrome warranted immediate cessation of
      thionamide. Improvement of the arthritis was seen in subsequent days. As there
      are no other reversible treatment modalities for Graves' disease in children,
      definitive treatment with radioactive iodine was needed to control the
      hyperthyroidism in this child. Antithyroid arthritis syndrome presenting as a
      migratory polyarthritis is a severe adverse effect of a common pediatric disease
      and should therefore be recognized by pediatricians. 

PMID- 25968433
TI  - Cerebral infarction and femoral venous thrombosis detected in a patient with
      diabetic ketoacidosis and heterozygous factor V Leiden G1691A and PAI-1 4G/5G
      mutations.
AB  - Cerebral infarction is one of the serious neurological complications of diabetic
      ketoacidosis (DKA). Especially in patients who are genetically prone to
      thrombosis, cerebral infarction may develop due to inflammation, dehydration, and
      hyperviscocity secondary to DKA. A 6-year-old child with DKA is diagnosed with
      cerebral infarction after respiratory insufficiency, convulsion, and altered
      level of consciousness. Femoral and external iliac venous thrombosis also
      developed in a few hours after central femoral catheter had been inserted.
      Heterozygous type of factor V Leiden and PAI-14G/5G mutation were detected. In
      patients with DKA, cerebral infarction may be suspected other than cerebral edema
      when altered level of consciousness, convulsion, and respiratory insufficiency
      develop and once cerebral infarction occurs the patients should also be evaluated
      for factor V Leiden and PAI-14G/5G mutation analysis in addition to the other
      prothrombotic risk factors. 

PMID- 25968434
TI  - Retrospective evaluation of pubertal development and linear growth of girls with
      Turner Syndrome treated with oral and transdermal estrogen.
AB  - OBJECTIVE: The objective of the study was to evaluate the pubertal development
      and linear growth of Turner Syndrome (TS) girls regularly monitored in our
      department. PATIENTS AND METHODS: The data of 13 patients with TS were evaluated
      retrospectively. Left hand radiograms were evaluated by three different pediatric
      endocrinologists to determine bone ages. RESULTS: Six (46.2%) of the TS girls
      were treated with oral estrogens, while 7 (53.8%) were treated with transdermal
      estrogen. The ratios of chronological age (CA) difference to bone age (BA)
      difference (DeltaCA/DeltaBA) in two groups of patients treated with estrogen were
      compared at the time of the last control. The DeltaCA/DeltaBA ratio in the
      transdermal estrogen-treated group was significantly higher (p=0.005). These
      results suggest slower BA progression in the TS girls treated with transdermal
      estrogen. CONCLUSION: BA advancement is less significant with transdermal
      estrogen, which is associated with adequate breast development.

PMID- 25968435
TI  - Novel mutations of DAX1 (NR0B1) in two Chinese families with X-linked adrenal
      hypoplasia congenita and hypogonadotropic hypogonadism.
AB  - OBJECTIVE: To analyze the DAX1 (NR0B1) (dosage-sensitive sex reversal-adrenal
      hypoplasia congenita (AHC) critical region on the X chromosome gene 1) gene in
      two Chinese families with AHC and hypogonadotrophic hypogonadism (HHG). PATIENTS
      AND METHODS: Two families with 4 affected males, 5 carrier females, and 4
      unaffected males were investigated. Sequencing of the entire 1413-bp coding
      region of DAX1 (NR0B1) gene was performed in both patients and their family
      members. RESULTS: Two different novel DAX1 (NR0B1) mutations located within exon
      1, an insertional mutation at codon 35 leading to a frameshift and a premature
      stop at codon 46, and a deletion mutation at codon 331 leading to a frameshift
      and a premature stop at codon 371 were detected. The mothers and sisters of the
      patients were heterozygotes for the mutations, while their fathers did not carry
      the mutations. CONCLUSIONS: Two novel DAX1 (NR0B1) mutations were detected in two
      Chinese families. These data indicate that molecular analysis of the DAX1 (NR0B1)
      gene is important for the diagnosis and genetic counseling of children with
      primary adrenal insufficiency.

PMID- 25968436
TI  - Persistent elevation of fibroblast growth factor 23 concentrations in healthy
      appropriate-for-gestational-age preterm infants.
AB  - OBJECTIVE: To explore the temporal evolution of 25-hydroxyvitamin D [25(OH)D],
      its epimer, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and
      minerals in healthy appropriate-for-gestational-age preterms. PATIENTS: A
      prospective study was undertaken in infants born at 28-32 weeks with monitoring
      at 1, 3, 5 weeks and term. METHODS: Morning plasma and urine calcium; phosphorus;
      creatinine; PTH, C-terminal and intact FGF23 (iFGF23) and liquid chromatography
      tandem mass spectrometry measurements of 25(OH)D were undertaken. Analyses
      included regression models. RESULTS: Some 11 infants (5 males) were recruited at
      a median gestational age of 31.2 weeks (interquartile range: 28.1-31.8). Standard
      chemistries were normal. No infant was vitamin D deficient; 58% achieved 50
      nmol/L with a median intake of 540 IU/day. High concentrations of C-3 epimer were
      detected. iFGF23 and C-terminal concentrations were persistently elevated (double
      and ten times adult norms, respectively). Tubular resorption of phosphorus was
      normal (88%+/-8%). CONCLUSIONS: Most infants achieved acceptable 25(OH)D3
      concentrations. The biologic significance of the elevated FGF23 is unclear.

PMID- 25968437
TI  - Dynamics of alkylresorcinols during rye caryopsis germination and early seedling
      growth.
AB  - Among secondary metabolites, alkylresorcinols are considered particularly
      important for the antimicrobial defense system in cereal grains. Dry rye
      caryopses and young seedlings contain detectable quantities of resorcinolic
      lipids. Overall, 11 distinct alkylresorcinol homologues were identified, which
      showed variable profiles during rye germination and early seedling development,
      especially with reference to the production of very long homologues and to side
      chain saturation. Additionally, changes in the alkylresorcinol composition during
      rye seedling growth are presented for the first time. 

PMID- 25968438
TI  - Inosine triphosphate pyrophosphohydrolase activity: more accurate predictor for
      ribavirin-induced anemia in hepatitis C infected patients than ITPA genotype.
AB  - BACKGROUND: ITPA polymorphisms have been associated with protection against
      ribavirin-induced anemia in chronic hepatitis C (HCV) patients. Here we
      determined the association of inosine triphosphate pyrophosphohydrolase (inosine
      triphosphatase or ITPase) enzyme activity with ITPA genotype in predicting
      ribavirin-induced anemia. METHODS: In a cohort of 106 HCV patients, hemoglobin
      (Hb) values were evaluated after 4 weeks (T4) and at the time of lowest Hb value
      (Tnadir). ITPase activity was measured and ITPA genotype determined. Single
      nucleotide polymorphisms (SNPs) tested were c.124+21A>C and c.94C>A. ITPase
      activity >=1.11 mU/mol Hb was considered as normal. RESULTS: After 4 weeks of
      treatment, 78% of the patients with normal ITPase activity were anemic and 21% of
      the patients with low ITPase activity (p<0.001). Stratified by genotype, the
      percentages of anemic patients were: wt/wt 76%, wt/c.124+21A>C 46% (p=0.068), and
      wt/c.94C>A 29% (p=0.021). At Tnadir, virtually all patients with normal ITPase
      activity were anemic, compared to only 64% of the patients with low activity
      (p=0.02). Thirteen patients had wt/c.124+241A>C genotype. Within this group all
      five patients with normal ITPase activity and only four of eight with decreased
      activity developed anemia. Presence of HCV RNA did not influence ITPase activity.
      CONCLUSIONS: This study is the first to report that ITPase activity predicts the
      development of anemia during ribavirin treatment. ITPase activity and ITPA
      genotype have high positive predictive values for development of ribavirin
      induced anemia at any time during treatment, but ITPase activity predicts
      ribavirin-induced anemia more accurately.

PMID- 25968439
TI  - Identification of the Learning Styles and "On-the-Job" Learning Methods
      Implemented by Nurses for Promoting Their Professional Knowledge and Skills.
AB  - The aim of this study was to identify the learning styles and methods used by
      nurses to promote their professional knowledge and skills. 928 nurses from 11
      hospitals across Israel completed 2 questionnaires, (1) Kolb's Learning Style
      Inventory, Version 3.1. and (2) the On-The-Job Learning Styles Questionnaire for
      the Nursing Profession. The most common learning style was the convergent style.
      The other learning styles were rated in the following descending order:
      accommodation, assimilation, and divergence. The on-the-job learning style
      consistently ranked highest was experience of relevant situations. On the other
      hand, seeking knowledge from books, journals, television, or the Internet was
      ranked lowest on all the indicators examined. With respect to general and on-the
      job learning styles, statistically significant differences were found between
      groups of nurses by: country of birth, gender, department, age, education, and
      role. Nurses required to take more personal responsibility for their own
      professional development by deepening their self-learning skills. 

PMID- 25968440
TI  - TopKLists: a comprehensive R package for statistical inference, stochastic
      aggregation, and visualization of multiple omics ranked lists.
AB  - High-throughput sequencing techniques are increasingly affordable and produce
      massive amounts of data. Together with other high-throughput technologies, such
      as microarrays, there are an enormous amount of resources in databases. The
      collection of these valuable data has been routine for more than a decade.
      Despite different technologies, many experiments share the same goal. For
      instance, the aims of RNA-seq studies often coincide with those of differential
      gene expression experiments based on microarrays. As such, it would be logical to
      utilize all available data. However, there is a lack of biostatistical tools for
      the integration of results obtained from different technologies. Although diverse
      technological platforms produce different raw data, one commonality for
      experiments with the same goal is that all the outcomes can be transformed into a
      platform-independent data format - rankings - for the same set of items. Here we
      present the R package TopKLists, which allows for statistical inference on the
      lengths of informative (top-k) partial lists, for stochastic aggregation of full
      or partial lists, and for graphical exploration of the input and consolidated
      output. A graphical user interface has also been implemented for providing access
      to the underlying algorithms. To illustrate the applicability and usefulness of
      the package, we integrated microRNA data of non-small cell lung cancer across
      different measurement techniques and draw conclusions. The package can be
      obtained from CRAN under a LGPL-3 license. 

PMID- 25968441
TI  - Co-administration of alpha-lipoic acid and glutathione is associated with no
      significant changes in serum bilirubin, alkaline phosphatase or gamma
      glutamyltranspeptidase levels during the treatment of neuroborreliosis with
      intravenous ceftriaxone.
AB  - BACKGROUND: While pharmacotherapy with intravenous ceftriaxone, a third
      generation cephalosporin, is a potential treatment of Lyme neuroborreliosis,
      there is concern that it can cause the formation of biliary sludge, leading to
      hepatobiliary complications such as biliary colic, jaundice and cholelithiasis,
      which are reflected in changes in serum levels of bilirubin and markers of
      cholestatic liver injury (alkaline phosphatase and gamma-glutamyltranspeptidase).
      It has been suggested that the naturally occurring substances alpha-lipoic acid
      and glutathione may be helpful in preventing hepatic disease. alpha-Lipoic acid
      exhibits antioxidant, anti-inflammatory and anti-apoptotic activities in the
      liver, while glutathione serves as a sulfhydryl buffer. The aim of this study was
      to determine whether co-administration of alpha-lipoic acid and glutathione is
      associated with significant changes in serum levels of bilirubin, alkaline
      phosphatase and gamma-glutamyltranspeptidase during the treatment of Lyme
      neuroborreliosis with long-term intravenous ceftriaxone. METHODS: Serum levels of
      bilirubin, alkaline phosphatase and gamma-glutamyltranspeptidase were measured in
      42 serologically positive Lyme neuroborreliosis patients before and after long
      term treatment with intravenous ceftriaxone (2-4 g daily) with co-administration
      of oral/intravenous alpha-lipoic acid (600 mg daily) and glutathione (100 mg
      orally or 0.6-2.4 g intravenously daily). RESULTS: None of the patients developed
      biliary colic and there were no significant changes in serum bilirubin, alkaline
      phosphatase or gamma-glutamyltranspeptidase levels over the course of the
      intravenous ceftriaxone treatment (mean length 75.0 days). CONCLUSIONS: Co
      administration of alpha-lipoic acid and glutathione is associated with no
      significant changes in serum bilirubin, alkaline phosphatase or gamma
      glutamyltranspeptidase levels during the treatment of neuroborreliosis with
      intravenous ceftriaxone.

PMID- 25968442
TI  - Effect of EphA7 Silencing on Proliferation, Invasion and Apoptosis in Human
      Laryngeal Cancer Cell Lines Hep-2 and AMC-HN-8.
AB  - AIMS: This study aimed to investigate the expression of EphA7 in human laryngeal
      squamous cell carcinoma (LSCC) tissues and disclose the potential roles and
      molecular mechanisms of EphA7 in LSCC. METHODS: In the present study, we examined
      EphA7 expression and its function and mechanism in LSCC. EphA7 expression levels
      were investigated by quantitative real-time PCR (qRT-PCR), western blotting, and
      immunohistochemistry in a panel of 35 LSCC patient cases. To investigate the
      potential mechanism of EphA7 in human laryngeal cancer, we employed EphA7 siRNA
      to knockdown EphA7 expression in LSCC cell line Hep-2 and AMC-HN-8. Subsequently,
      MTT, TUNEL, qRT-PCR, and western blotting were performed to disclose the roles of
      EphA7 on proliferation, invasion and migration, and apoptosis in LSCC cell line
      Hep-2 and AMC-HN-8. RESULTS: Depletion of EphA7 remarkably inhibited the
      proliferation and invasion of Hep-2 and AMC-HN-8 cells in comparison to control
      and EphA7 siRNA negative control (NC)-transfected cells. TUNEL staining assay
      demonstrated that, compared with the control group, the rate of apoptosis in the
      EphA7 siRNA group was significantly increased. In addition, knockdown of EphA7 in
      Hep-2 or AMC-HN-8 cells markedly decreased the expression of EphA7 and PTEN,
      which could contribute to apoptosis. However, the bpV(phen), a PTEN inhibitor,
      could attenuate anti-proliferation and pro-apoptotic effects of EphA7 siRNA in
      Hep-2 and AMC-HN-8 cells. CONCLUSION: Up-regulation of EphA7 was observed in
      human LSCC samples and down-regulation of EphA7 effectively suppressed laryngeal
      carcinoma cell growth and promoted its apoptosis. Thus, EphA7 has a critical role
      in modulating cell growth and apoptosis, which serves as a potential therapeutic
      target in human LSCC.

PMID- 25968443
TI  - Insomnia (primary) in older people: non-drug treatments.
AB  - INTRODUCTION: Up to 40% of older adults have insomnia, with difficulty getting to
      sleep, early waking, or feeling unrefreshed on waking. The prevalence of insomnia
      increases with age. Other risk factors include psychological factors, stress,
      daytime napping, and hyperarousal. METHODS AND OUTCOMES: We conducted a
      systematic review and aimed to answer the following clinical question: What are
      the effects of non-drug treatments for primary insomnia in older people (aged 60
      years and older)? We searched: Medline, Embase, The Cochrane Library, and other
      important databases up to May 2014 (Clinical Evidence reviews are updated
      periodically; please check our website for the most up-to-date version of this
      review). We included harms alerts from relevant organisations such as the US Food
      and Drug Administration (FDA) and the UK Medicines and Healthcare products
      Regulatory Agency (MHRA). RESULTS: We found 14 studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review, we present information
      relating to the effectiveness and safety of the following interventions:
      cognitive behavioural therapy for insomnia (CBT-I), exercise programmes, and
      timed exposure to bright light.

PMID- 25968445
TI  - Relationship and interaction between serum sodium concentration and portal
      hemodynamics in patients with cirrhosis.
AB  - BACKGROUND AND AIM: To examine the relationship between hyponatremia and portal
      hemodynamics and their effect on the prognosis of cirrhosis. METHODS: Portal
      hemodynamic parameters measured by Doppler ultrasound and serum sodium
      concentrations were examined in 153 cirrhosis patients (mean age 62.2 +/- 12.0
      years; median observation period, 34.1 m). RESULTS: Study participants included
      16 patients with hyponatremia (Na < 135 mEq/L), who showed a significantly
      greater frequency of possessing a splenorenal shunt (SRS; P = 0.0068), and 137
      patients without hyponatremia. Serum sodium concentrations were significantly
      lower in patients with SRS than in those without (P = 0.0193). An increased
      prothrombin time-international normalized ratio was a significant predictive
      factor for developing hyponatremia a year later (8/96; Hazard ratio 14.415; P =
      0.028). The cumulative survival rate was significantly lower in patients with
      hyponatremia (46.7% at 1 and 3 years) than in those without (91.8% at 1 year,
      76.8% at 3 years; P < 0.001). The cumulative survival rate was significantly
      lower in patients who had developed hyponatremia after 1 year (100% at 1 year,
      62.5% at 3 years) than those who had not (100% at 1 year, 89.0% at 3 years; P <
      0.001). The cumulative survival rate was significantly worse in patients with
      both hyponatremia and SRS (20% at 1 year). CONCLUSIONS: There was a close linkage
      between the serum sodium concentration and portal hemodynamic abnormality,
      presence of SRS, and their interaction may negatively influence the prognoses in
      cirrhosis.

PMID- 25968444
TI  - Rocky milieu: challenges of effective integration of clinical risk management
      into hospitals in Iran.
AB  - Healthcare risks and clinical risks have been recognized as a major challenge in
      healthcare. Clinical risks can never be eliminated and can have serious adverse
      effects on patient safety. Thus, a clinical risk management (CRM) system has been
      introduced in the healthcare system to improve quality services. The aim of this
      study was to explore nurses' experiences related to the challenges of
      implementing CRM in the organizational context. This qualitative study was based
      on the conventional content analysis of the Lundman and Graneheim approach, and
      it consisted of 22 interview sessions with 20 nurses. The purposive sampling
      method was used to choose the participants from three hospitals affiliated with
      the Kerman University of Medical Sciences. We used semi-structured interviews and
      review of relevant documents to collect data. The analysis of the data led to the
      emergence of "rocky milieu" as the main theme, and it consisted of three
      categories that, along with their subcategories, explain the challenges of
      implementing CRM. The three categories and their subcategories were (1)
      organizational culture and leadership challenges (decision and performance of
      leadership and cultural resistance to change), (2) limitation of resources
      (financial, human, and physical and equipment resources), and (3) variations and
      complexities in working conditions (the emotional, psychological, and social
      atmosphere and the heaviness of workload). Attempts have been made to establish
      CRM through clinical governance and accreditation, but organizational challenges
      have created a rocky milieu for implementing CRM. However, from an organizational
      context concerning the suitability of healthcare in Iran, there are obvious needs
      to move toward quality improvement and safe practices through the effective
      implementation of CRM. 

PMID- 25968446
TI  - Mapping the minds of the mediators: The cognitive frames of climate journalists
      from five countries.
AB  - This article is based on the premise that journalists play an important role as
      mediators of scientific information and their interpretations of climate change
      influence media debates and public opinion. The study maps the minds of climate
      journalists from five different countries (Germany, India, Switzerland, the
      United Kingdom, and the United States) and different types of leading media
      outlets. It identifies five cognitive frames that vary between attributing the
      responsibility for climate change to lobbying and national interests, blaming
      consumerist culture and the capitalist system, and expressing technological
      optimism. The study provides evidence for the emergence of a sustainability
      frame, indicates a "blame game" between industrialized countries and emerging
      economies, and shows the demand for a global ecological discourse. Finally, it
      explores how individual factors such as specialization, professional aims, and
      political alignment correlate with the cognitive frames of journalists.

PMID- 25968447
TI  - Benzodiazepines May be Worse Than Opioids: Negative Medication Effects in Severe
      Chronic Pain.
AB  - OBJECTIVES: Opioid prescription for noncancer pain is increasing in Europe and
      the United States. Research and guidance have focused on the potential for
      dependency and medical side effects with high doses. In contrast, benzodiazepines
      have received little attention in the chronic pain literature, despite evidence
      for dependency and cognitive impairment in long-term use. We aimed to examine the
      relationship between these classes of medication use, mood, and functioning.
      METHODS: This cross-sectional study included patients (N=229) with disabling
      chronic pain who were about to start intensive pain rehabilitation. They
      completed self-report measures of mood, functioning, and responses to pain. We
      examined each patient's medication use and calculated a single morphine
      equivalent (ME) dose per person, and a similar diazepam equivalent (DE) dose. We
      examined the relationship between drug dose, mood, and functioning. RESULTS:
      Higher DE doses were associated with worse outcomes in most domains. Higher ME
      doses were more narrowly associated with worse functioning. There was no evidence
      for any benefit of these drugs; higher doses were not associated with less pain,
      fear, or disability. Higher ME doses were not more problematic, contrary to our
      predictions. The combination of opioids and benzodiazepines was associated with
      particularly poor outcomes for mood. DISCUSSION: This study is the first to
      examine both opioid and benzodiazepine use together in chronic pain. We found the
      anticipated negative effects of opioid medication, and particularly consistent
      associations between benzodiazepine use and poor well-being. Future guidance on
      chronic pain prescription should focus on restricting benzodiazepine use.

PMID- 25968448
TI  - Hormonal and Clinical Predictors for Post-egg Retrieval Pain in Women Undergoing
      Assisted Reproductive Technology Procedures.
AB  - OBJECTIVES: The intensity of post-egg retrieval pain is underestimated, with few
      studies examining postprocedural pain and predictors to identify women at risk
      for severe pain. We evaluated the influence of preprocedural hormonal levels,
      ovarian factors, and mechanical temporal summation (mTS) as predictors for post
      egg retrieval pain in women undergoing in vitro fertilization. METHODS: Eighteen
      women scheduled for ultrasound-guided egg retrieval under standardized anesthesia
      and postprocedural analgesia were enrolled. Preprocedural mTS, questionnaires,
      clinical data related to anesthesia and the procedure itself, postprocedural pain
      scores, and pain medication for breakthrough pain were recorded. Statistical
      analysis included Pearson product-moment correlations, Mann-Whitney U tests, and
      multiple linear regressions. RESULTS: Average peak post-egg retrieval pain during
      the first 24 hours was 5.0+/-1.6 on a numerical response scale (0=no pain,
      10=worst pain imaginable). Peak post-egg retrieval pain was correlated with basal
      antimullerian hormone (AMH) (r=0.549, P=0.018), preprocedural peak estradiol
      (r=0.582, P=0.011), total number of follicles (r=0.517, P=0.028), and number of
      retrieved eggs (r=0.510, P=0.031). Ovarian hyperstimulation syndrome (n=4) was
      associated with higher basal AMH (P=0.004), higher peak pain scores (P=0.049),
      but not with peak estradiol (P=0.13). The mTS did not correlate with peak
      postprocedural pain (r=0.266, P=0.286), or peak estradiol level (r=0.090,
      P=0.899). DISCUSSION: Peak post-egg retrieval pain intensity was higher than
      anticipated. Our results suggest that post-egg retrieval pain can be predicted by
      baseline AMH, high peak estradiol, and ovarian hyperstimulation syndrome. Further
      studies to evaluate intraprocedural and postprocedural pain in this population
      are needed, as well as clinical trials to assess postprocedural analgesia in
      women presenting with high hormonal levels.

PMID- 25968449
TI  - Pain-related Sleep Disturbance: A Prospective Study With Repeated Measures.
AB  - OBJECTIVES: Pain has been found to be associated with poor sleep quality,
      awakenings, and shorter sleep time. There is a need to understand the
      relationship of pain and sleep over time to adequately manage the pain disorder
      and its consequences. The objectives of this study were to establish the
      prevalence of sleep disturbance in patients with acute or persistent low back
      pain (LBP), to investigate the correlation between pain and sleep disturbance and
      to explore the influence of pain on sleep disturbance. MATERIALS AND METHODS:
      Data from a prospective observational study of 233 patients with acute and
      persistent LBP were used. Twenty-six weekly pain reports and monthly (weeks 2, 6,
      10, 14, 18, 22, and 26) sleep reports were collected with text messages. The
      prevalence of sleep disturbance, the correlation of pain and sleep disturbance,
      and the risk of reporting disturbed sleep after experiencing LBP were calculated.
      RESULTS: Sleep disturbance was reported by 67% of the sample. Among patients with
      acute and persistent LBP, the prevalence was 55% and 76%, respectively. Measures
      of pain and sleep disturbance were significantly correlated. Compared with being
      pain free, the risk of reporting sleep disturbance after experiencing pain the
      previous week was significantly increased (relative risk=2.1 to 5.8), and a dose
      response between the number of days with pain and the risk of sleep disturbance
      was found. DISCUSSION: This study used repeated measures of both pain and sleep
      disturbance. The results were in line with previous research, confirming that
      sleep disturbance was found in the majority of patients with LBP. Pain and sleep
      measures were significantly correlated, and there was an increased risk of
      reporting sleep disturbance after experiencing LBP.

PMID- 25968450
TI  - Sympathetic Dysfunction in Patients With Chronic Low Back Pain and Failed Back
      Surgery Syndrome.
AB  - BACKGROUND: Chronic low back pain (CLBP) is defined as pain that persists longer
      than 12 weeks and is often attributed to degenerative or traumatic conditions of
      the spine. Failed back surgery syndrome is a condition in which chronic pain
      persists after spinal surgery. Electrodiagnostic studies can be used to confirm
      the diagnosis of lumbosacral radiculopathy, but other diagnostic methods are
      often needed to assess sympathetic nervous system dysfunction. OBJECTIVES: The
      aim of this study was to investigate the affection of sympathetic skin response
      (SSR) in cases of chronic low back pain (LBP) and failed back surgery syndrome
      (FBSS) and to assess the association of SSR abnormalities with perceived
      functional disability and pain among these patients. METHODOLOGY: Twenty patients
      with CLBP and 10 patients with failed FBSS who fulfilled the inclusion criteria
      were recruited to the present study. All cases had back, leg, or back and leg
      pain of at least 3-month duration or following spinal surgery. The control group
      consists of 10 healthy participants matched in age and sex. Electrophysiologic
      nerve conduction studies and SSR recording were applied on the symptomatic and
      normal side in study cases and on both sides in the control group. Pain intensity
      was analyzed by the visual analogue scale (VAS) and perceived functional
      disability was assessed with the Oswestry disability index (ODI). CONCLUSIONS: It
      was concluded that the sympathetic nervous system is affected in CLBP and FBSS
      patients with abnormalities in SSR and that the dysfunction of sympathetic
      nervous system may contribute to the intensity and chronicity of pain in these
      groups of patients. Moreover, a strong association was found between SSR and
      functional disabilities in these patients.

PMID- 25968451
TI  - Pregabalin in Patients With Painful Diabetic Peripheral Neuropathy Using an NSAID
      for Other Pain Conditions: A Double-Blind Crossover Study.
AB  - OBJECTIVES: To evaluate pregabalin's efficacy and safety versus placebo to reduce
      pain in patients with diabetic peripheral neuropathy (DPN) using a concomitant
      nonsteroidal anti-inflammatory drug. MATERIALS AND METHODS: In a randomized,
      double-masked, 14-week, 2-period, crossover study, patients with painful DPN
      using a nonsteroidal anti-inflammatory drug for non-DPN-related pain received 150
      to 300 mg/d pregabalin or placebo (period 1); 14-day washout; then, the opposite
      therapy (period 2). Endpoints included weekly change in DPN pain score, sleep
      interference, adverse events, and patient-reported outcomes. RESULTS: Patients
      with similar baseline characteristics were randomized (period 1) to 1 of the 2
      following possible sequences: pregabalin->placebo (n=154) or placebo->pregabalin
      (n=147). Results of the primary efficacy measure, mean weekly DPN pain at
      endpoint, showed no significant difference between pregabalin and placebo.
      However, 1 sensitivity analysis (mixed-model repeated measures) found greater
      pain score reductions with pregabalin than placebo at weeks 2 to 4 and overall
      (all P<0.05). One secondary endpoint analysis, mean treatment difference in DPN
      related sleep interference, favored pregabalin over placebo (P=0.0009). Other
      sensitivity and secondary analyses were nonsignificant. Treatment-emergent
      adverse events were consistent with the known safety profile of pregabalin.
      DISCUSSION: Pregabalin (vs. placebo) showed overall improvements in sleep, pain
      reduction in 1 sensitivity analysis, and was well tolerated. Potential factors
      that may have confounded the ability to detect a treatment difference in DPN pain
      reduction (high placebo response, carryover effect, short washout period, or
      pregabalin dose) are discussed in the context of future studies.

PMID- 25968452
TI  - Editorial: Attention-deficit/hyperactivity disorder: a continuing challenge to
      researchers, practitioners and carers.
AB  - This editorial introduces a collection of research papers and a review on ADHD,
      highlighting the continuing challenge that ADHD poses in research and practice.
      The articles include a Practitioner Review providing a comprehensive review
      focusing on current knowledge about barriers and facilitators operating at the
      individual, organisational and societal level; a study reporting a randomised
      controlled trial of parent training for ADHD pre-schoolers; an empirical paper on
      sex differences in ADHD symptom severity; a study of the co-development of ADHD
      and externalizing behaviour across the lifespan; a study of the genetic
      architecture of neurocognitive abilities in the general population; and finally a
      study examining the differential association among three behavioural dimensions
      leading to early-onset conduct problems. 

PMID- 25968453
TI  - Oral administration of Lactobacillus casei variety rhamnosus partially alleviates
      TMA-induced atopic dermatitis in mice through improving intestinal microbiota.
AB  - AIMS: The purpose of this study was to investigate the effect of Lactobacillus
      casei variety rhamnosus (LCR35) on Atopic dermatitis (AD)-like symptoms in mice.
      METHODS AND RESULTS: AD-like skin lesions in BALB/C mice were induced by
      sensitization and subsequent repeated challenges with trimellitic anhydride (TMA)
      for 10 days. LCR35 was orally administered to the mice once daily throughout the
      study. In the TMA-induced AD model, orally administered LCR35 suppressed
      significantly irritant-related scratching behaviour and skin dehydration as well
      as apparent severity of AD. LCR35 also significantly decreased serum levels of
      IgE and IL-4, but not IFN-gamma, implying the restoration of TMA-induced
      disruption of Th1/Th2 balance. Quantitative real-time PCR targeting hypervariable
      regions of 16S rDNA gene of faecal microbiota indicated that the LCR35 treatment
      increased the population of Bifidobacterium, Lactobacilli, Enterococcus and
      Bacteroides fragilis group, but decreased those of Clostridium coccoides group.
      CONCLUSIONS: LCR35 has the ability to suppress the development of AD in mice,
      possibly through the modulation of Th1/Th2 balance and gut microbiota.
      SIGNIFICANCE AND IMPACT OF THE STUDY: LCR35 has a strong potential as a probiotic
      for preventing AD.

PMID- 25968454
TI  - Molecular and Cytological Comparisons of Chromosomes 7el1, 7el2, 7E(e), and 7E i
      Derived from Thinopyrum.
AB  - Thinopyrum chromosomes 7el1, 7el2, 7E(e), and 7E(i), homoeologous to group 7
      chromosomes of common wheat (Triticum aestivum), were determined to have many
      useful agronomical traits for wheat improvement. To analyze the genetic
      relationships among the 4 Thinopyrum 7E chromosomes, the conserved orthologous
      set markers, genomic in situ hybridization (GISH), and meiotic chromosome pairing
      were used in this study. The unweighted pair-group method with arithmetical
      averages (UPGMA) analysis indicated that 7el1, derived from T. ponticum, and
      7E(i), derived from T. intermedium, were the most closely related. 7el2, derived
      from T. ponticum, was relatively distant from the 7el1-7E(i) complex. While
      7E(e), derived from T. elongatum, was more distantly related to 7el1, 7el2, and
      7E(i). This is the first report showing that 7el1 and 7E(i) may be similar, which
      could be explained by the similar chromosome signal distribution revealed by GISH
      as well as UPGMA analysis revealed by both molecular markers and the highest
      frequency of meiotic pairing. The newly developed genome-specific molecular
      markers may be useful for marker-assisted selection of Lr19, Bdv3, and Fhblop.

PMID- 25968455
TI  - Preexisting Levels of CD4 T Cells Expressing PD-1 Are Related to Overall Survival
      in Prostate Cancer Patients Treated with Ipilimumab.
AB  - Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) blockade can induce tumor
      regression and improved survival in cancer patients. This treatment can enhance
      adaptive immune responses without an exogenous vaccine, but the immunologic
      biomarkers associated with improved clinical outcome in cancer patients are not
      fully established. A phase Ib trial in patients with metastatic, castration
      resistant prostate cancer was performed combining ipilimumab with sargramostim
      (GM-CSF). In addition to evaluating ipilimumab dose, patients were followed
      clinically for response and overall survival, and for immunomodulation of
      circulating T cells. PSA declines of >=50% and radiographic responses were
      observed at doses of >=3 mg/kg/dose. Timing of clinical responses could be either
      immediate or delayed. Durable responses were also observed off treatment. A
      subset of patients experienced long-term survival with or without objective
      clinical responses. The relationship between T-cell phenotype in peripheral blood
      and overall survival was examined retrospectively. We found that the treatment
      induced an increase in the levels of CD4(+) effector T (Teff) cells, regulatory T
      cells, PD-1(+) CD4 Teff cells, and PD-1(+) CD8 T cells. However, these increased
      levels were not associated with overall survival. Instead, low pretreatment
      baseline levels of PD-1(+) CD4 Teff cells were found to correlate with longer
      overall survival. Furthermore, baseline levels of PD-1(+) CD4 Teff cells from
      patients with shorter overall survival were higher than from cancer-free male
      control subjects. These results suggest that preexisting expression of
      immunologic checkpoint marker PD-1 on CD4 Teff cells may help identify patients
      that may benefit from ipilimumab treatment.

PMID- 25968456
TI  - Interleukin-6/STAT3 Pathway Signaling Drives an Inflammatory Phenotype in Group A
      Ependymoma.
AB  - Ependymoma (EPN) in childhood is a brain tumor with substantial mortality.
      Inflammatory response has been identified as a molecular signature of high-risk
      Group A EPN. To better understand the biology of this phenotype and aid
      therapeutic development, transcriptomic data from Group A and B EPN patient tumor
      samples, and additional malignant and normal brain data, were analyzed to
      identify the mechanism underlying EPN Group A inflammation. Enrichment of IL6 and
      STAT3 pathway genes were found to distinguish Group A EPN from Group B EPN and
      other brain tumors, implicating an IL6 activation of STAT3 mechanism. EPN tumor
      cell growth was shown to be dependent on STAT3 activity, as demonstrated using
      shRNA knockdown and pharmacologic inhibition of STAT3 that blocked proliferation
      and induced apoptosis. The inflammatory factors secreted by EPN tumor cells were
      shown to reprogram myeloid cells, and this paracrine effect was characterized by
      a significant increase in pSTAT3 and IL8 secretion. Myeloid polarization was
      shown to be dependent on tumor secretion of IL6, and these effects could be
      reversed using IL6-neutralizing antibody or IL6 receptor-targeted therapeutic
      antibody tocilizumab. Polarized myeloid cell production of IL8 drove unpolarized
      myeloid cells to upregulate CD163 and to produce a number of proinflammatory
      cytokines. Collectively, these findings indicate that constitutive IL6/STAT3
      pathway activation is important in driving tumor growth and inflammatory cross
      talk with myeloid cells within the Group A EPN microenvironment. Effective design
      of Group A-targeted therapy for children with EPN may require reversal of this
      potentially immunosuppressive and protumor pathway.

PMID- 25968458
TI  - Review cyclic peptides on a merry-go-round; towards drug design.
AB  - Peptides and proteins are attractive initial leads for the rational design of
      bioactive molecules. Several natural cyclic peptides have recently emerged as
      templates for drug design due to their resistance to chemical or enzymatic
      hydrolysis and high selectivity to receptors. The development of practical
      protocols that mimic the power of nature's strategies remains paramount for the
      advancement of novel peptide-based drugs. The de novo design of peptide mimetics
      (nonpeptide molecules or cyclic peptides) for the synthesis of linear or cyclic
      peptides has enhanced the progress of therapeutics and diverse areas of science
      and technology. In the case of metabolically unstable peptide ligands, the
      rational design and synthesis of cyclic peptide analogues has turned into an
      alternative approach for improved biological activity.

PMID- 25968457
TI  - Special Conference on Tumor Immunology and Immunotherapy: A New Chapter.
AB  - The overall objective of the fifth American Association for Cancer Research
      Special Conference, "Tumor Immunology and Immunotherapy: A New Chapter,"
      organized by the Cancer Immunology Working Group, was to highlight
      multidisciplinary approaches of immunotherapy and mechanisms related to the
      ability of immunotherapy to fight established tumors. With the FDA approval of
      sipuleucel-T, ipilimumab (anti-CTLA-4; Bristol-Myers Squibb), and the two anti-PD
      1 antibodies, pembrolizumab (formerly MK-3475 or lambrolizumab; Merck) and
      nivolumab (Bristol-Myers Squibb), immunotherapy has become a mainstream treatment
      option for some cancers. Many of the data presented at the conference and
      reviewed in this article showcase the progress made in determining the
      mechanistic reasons for the success of some treatments and the mechanisms
      associated with tolerance within the tumor microenvironment, both of which are
      potential targets for immunotherapy. In addition to combination and multimodal
      therapies, improvements in existing therapies will be needed to overcome the
      numerous ways that tumor-specific tolerance thwarts the immune system. This
      conference built upon the success of the 2012 conference and focused on seven
      progressing and/or emerging areas-new combination therapies, combination
      therapies and vaccine improvement, mechanisms of antibody therapy, factors in the
      tumor microenvironment affecting the immune response, the microbiomes effect on
      cancer and immunotherapy, metabolism in immunotherapy, and adoptive T-cell
      therapy. Cancer Immunol Res; 3(6); 1-8. (c)2015 AACR.

PMID- 25968459
TI  - A multi-locus approach resolves the phylogenetic relationships of the Simulium
      asakoae and Simulium ceylonicum species groups in Malaysia: evidence for distinct
      evolutionary lineages.
AB  - A multi-locus approach was used to examine the DNA sequences of 10 nominal
      species of blackfly in the Simulium subgenus Gomphostilbia (Diptera: Simuliidae)
      in Malaysia. Molecular data were acquired from partial DNA sequences of the
      mitochondria-encoded cytochrome c oxidase subunit I (COI), 12S rRNA and 16S rRNA
      genes, and the nuclear-encoded 18S rRNA and 28S rRNA genes. No single gene, nor
      the concatenated gene set, resolved all species or all relationships. However,
      all morphologically established species were supported by at least one gene. The
      multi-locus sequence analysis revealed two distinct evolutionary lineages,
      conforming to the morphotaxonomically recognized Simulium asakoae and Simulium
      ceylonicum species groups. 

PMID- 25968461
TI  - Highly sensitive and robust peroxidase-like activity of porous nanorods of ceria
      and their application for breast cancer detection.
AB  - Porous nanorods of ceria (PN-Ceria), a novel ceria nanostructure with a large
      surface area and a high surface Ce(3+) fraction, exhibited strong intrinsic
      peroxidase activity toward a classical peroxidase substrate in the presence of
      H2O2. Peroxidase-like activity of ceria originated from surface Ce(3+) species as
      the catalytic center, thereby explaining the high performance of PN-Ceria as an
      artificial enzyme mimicking peroxidase. Compared with the natural enzyme
      horseradish peroxidase (HRP), PN-Ceria showed several advantages such as low
      cost, easy storage, high sensitivity, and, prominently, chemical and catalytic
      stability under harsh conditions. Importantly, the enzymatic activity of PN-Ceria
      remained nearly constant and stable over a wide range of temperature and pH
      values, ensuring the accuracy and reliability of measurements of its peroxidase
      like activity. A PN-Ceria based novel diagnostic system was developed for breast
      cancer detection with a higher sensitivity than the standard HRP detection
      system. Our work has laid a solid foundation for the development of PN-Ceria as a
      novel diagnostic tool for clinical use. 

PMID- 25968460
TI  - Utility of characters evolving at diverse rates of evolution to resolve quartet
      trees with unequal branch lengths: analytical predictions of long-branch effects.
AB  - BACKGROUND: The detection and avoidance of "long-branch effects" in phylogenetic
      inference represents a longstanding challenge for molecular phylogenetic
      investigations. A consequence of parallelism and convergence, long-branch effects
      arise in phylogenetic inference when there is unequal molecular divergence among
      lineages, and they can positively mislead inference based on parsimony
      especially, but also inference based on maximum likelihood and Bayesian
      approaches. Long-branch effects have been exhaustively examined by simulation
      studies that have compared the performance of different inference methods in
      specific model trees and branch length spaces. RESULTS: In this paper, by
      generalizing the phylogenetic signal and noise analysis to quartets with uneven
      subtending branches, we quantify the utility of molecular characters for
      resolution of quartet phylogenies via parsimony. Our quantification incorporates
      contributions toward the correct tree from either signal or homoplasy (i.e. "the
      right result for either the right reason or the wrong reason"). We also
      characterize a highly conservative lower bound of utility that incorporates
      contributions to the correct tree only when they correspond to true, unobscured
      parsimony-informative sites (i.e. "the right result for the right reason"). We
      apply the generalized signal and noise analysis to classic quartet phylogenies in
      which long-branch effects can arise due to unequal rates of evolution or an
      asymmetrical topology. Application of the analysis leads to identification of
      branch length conditions in which inference will be inconsistent and reveals
      insights regarding how to improve sampling of molecular loci and taxa in order to
      correctly resolve phylogenies in which long-branch effects are hypothesized to
      exist. CONCLUSIONS: The generalized signal and noise analysis provides analytical
      prediction of utility of characters evolving at diverse rates of evolution to
      resolve quartet phylogenies with unequal branch lengths. The analysis can be
      applied to identifying characters evolving at appropriate rates to resolve
      phylogenies in which long-branch effects are hypothesized to occur.

PMID- 25968463
TI  - Attuning hydroxypropyl methylcellulose phthalate to oral delivery vehicle for
      effective and selective delivery of protein vaccine in ileum.
AB  - Orally delivered proteins or antigens are taken up by epithelial microfold cells
      (M cells) in Peyer's patches, especially abundant in the ileum of small
      intestine. However, several barriers including gastric pH, enzymatic degradation,
      rapid transit and lack of specificity of proteins towards M cells, has made the
      goal of oral delivery of proteins very challenging. To overcome the problems, we
      developed an ileum targeted protein delivery system using hydroxypropyl
      methylcellulose phthalate (HPMCP). Initially, we attuned pH-sensitive property of
      HPMCP for controlled dissolution at ileum pH (>=7.4) by thiolation. Thiolation
      also improved mucoadhesive property of HPMCP to prolong the particles transit
      time through the gastrointestinal tract. Typically, thiolated HPMCP (T-HPMCP)
      prevented protein release in acidic pH in stomach and duodenum but released the
      proteins at ileal pH in a controlled manner. To evaluate the effectiveness of an
      oral delivery vehicle, T-HPMCP was used to deliver an M cell targeting protein
      antigen to mice through oral route. The antigens were mostly delivered and
      located in Peyer's patches in the ileum demonstrating the higher uptake of
      antigens through M-cells. Importantly, oral delivery of the antigen with T-HPMCP
      not only induced strong antibody mediated immune responses but also generated
      memory T cells in the spleen as adaptive immunity indicating a direct evidence of
      an effective delivery system. Thus, this study represents the first demonstration
      of HPMCP for ileum-specific delivery of protein vaccine through oral route. 

PMID- 25968462
TI  - Phytomolecule icaritin incorporated PLGA/TCP scaffold for steroid-associated
      osteonecrosis: Proof-of-concept for prevention of hip joint collapse in bipedal
      emus and mechanistic study in quadrupedal rabbits.
AB  - Steroid-associated osteonecrosis (SAON) may lead to joint collapse and subsequent
      joint replacement. Poly lactic-co-glycolic acid/tricalcium phosphate (P/T)
      scaffold providing sustained release of icaritin (a metabolite of Epimedium
      derived flavonoids) was investigated as a bone defect filler after surgical core
      decompression (CD) to prevent femoral head collapse in a bipedal SAON animal
      model using emu (a large flightless bird). The underlying mechanism on SAON was
      evaluated using a well-established quadrupedal rabbit model. Fifteen emus were
      established with SAON, and CD was performed along the femoral neck for the
      efficacy study. In this CD bone defect, a P/T scaffold with icaritin (P/T/I
      group) or without icaritin (P/T group) was implanted while no scaffold
      implantation was used as a control. For the mechanistic study in rabbits, the
      effects of icaritin and composite scaffolds on bone mesenchymal stem cells
      (BMSCs) recruitment, osteogenesis, and anti-adipogenesis were evaluated. Our
      efficacy study showed that P/T/I group had the significantly lowest incidence of
      femoral head collapse, better preserved cartilage and mechanical properties
      supported by more new bone formation within the bone tunnel. For the mechanistic
      study, our in vitro tests suggested that icaritin enhanced the expression of
      osteogenesis related genes COL1alpha, osteocalcin, RUNX2, and BMP-2 while
      inhibited adipogenesis related genes C/EBP-beta, PPAR-gamma, and aP2 of rabbit
      BMSCs. Both P/T and P/T/I scaffolds were demonstrated to recruit BMSCs both in
      vitro and in vivo but a higher expression of migration related gene VCAM1 was
      only found in P/T/I group in vitro. In conclusion, both efficacy and mechanistic
      studies show the potential of a bioactive composite porous P/T scaffold
      incorporating icaritin to enhance bone defect repair after surgical CD and
      prevent femoral head collapse in a bipedal SAON emu model.

PMID- 25968465
TI  - Risk factors for elevated blood lead levels among children aged 6-36 months
      living in Greece.
AB  - BACKGROUND: Childhood lead poisoning remains a critical environmental health
      concern because even low blood lead levels (BLLs) can result in permanent adverse
      health effects. Social factors and living conditions have been correlated with
      BLLs. There is no recent survey about the prevalence of elevated BLLs among
      children in Greece. The purpose of this study was to assess BLLs among children
      aged 6-36 months born and living in Greece and to evaluate their association with
      demographic, socio-economic and housing conditions. METHODS: In a cross-sectional
      hospital-based study including 814 randomly selected children aged 6-36 months,
      BLLs and haematological parameters were evaluated. A questionnaire investigating
      demographic and socio-economic conditions was completed in all children.
      Statistical analysis was performed using STATA for Windows v.8.5, and P < 0.05
      was considered statistically significant. RESULTS: The mean BLLs of the
      population were 2.78 (SD = 2.34) ug/dl, and the median was 2.02 ug/dl; 11.7% had
      BLLs above 5 ug/dl, while 15 children (1.8%) exceeded 10 ug/dl. Being a toddler,
      being Roma or Asian, living in an industrial/low-income neighbourhood or in an
      old house, using traditional herbs and/or spices and having a mother with a
      manual occupation were independent risk factors for elevated BLLs. CONCLUSION:
      Lead exposure remains a threat for optimal health especially for toddlers and
      children of socio-economically disadvantaged families living in Greece. A
      nationwide survey to assess lead exposure in children is necessary to guide
      prevention governmental policies.

PMID- 25968464
TI  - Inhibition of MAP kinase/NF-kB mediated signaling and attenuation of
      lipopolysaccharide induced severe sepsis by cerium oxide nanoparticles.
AB  - Sepsis is a life threatening disease that is associated with high mortality.
      Existing treatments have failed to improve survivability in septic patients. The
      purpose of this present study is to evaluate whether cerium oxide nanoparticles
      (CeO2NPs) can prevent lipopolysaccharide (LPS) induced severe sepsis mortality by
      preventing hepatic dysfunction in male Sprague Dawley rats. Administration of a
      single dose (0.5 mg/kg) of CeO2NPs intravenously to septic rats significantly
      improved survival rates and functioned to restore body temperature, respiratory
      rate and blood pressure towards baseline. Treatment-induced increases in animal
      survivability were associated with decreased hepatic damage along with reductions
      in serum cytokines/chemokines, and diminished inflammatory related signaling.
      Kupffer cells and macrophage cells exposed to CeO2NPs exhibited decreases in LPS
      induced cytokine release (TNF-alpha, IL-1beta, IL-6, HMGB1) which were associated
      with diminished cellular ROS, reduced levels of nitric oxide synthase (iNOS),
      cyclooxygenase 2 (COX-2), and decreased nuclear factor-kappa light chain enhancer
      of activated B cells (NF-kB) transcriptional activity. The findings of this study
      indicate that CeO2NPs may be useful as a therapeutic agent for sepsis.

PMID- 25968466
TI  - Contrasting host-pathogen interactions and genome evolution in two generalist and
      specialist microsporidian pathogens of mosquitoes.
AB  - Obligate intracellular pathogens depend on their host for growth yet must also
      evade detection by host defenses. Here we investigate host adaptation in two
      Microsporidia, the specialist Edhazardia aedis and the generalist Vavraia
      culicis, pathogens of disease vector mosquitoes. Genomic analysis and deep RNA
      Seq across infection time courses reveal fundamental differences between these
      pathogens. E. aedis retains enhanced cell surface modification and signalling
      capacity, upregulating protein trafficking and secretion dynamically during
      infection. V. culicis is less dependent on its host for basic metabolites and
      retains a subset of spliceosomal components, with a transcriptome broadly focused
      on growth and replication. Transcriptional profiling of mosquito immune responses
      reveals that response to infection by E. aedis differs dramatically depending on
      the mode of infection, and that antimicrobial defensins may play a general role
      in mosquito defense against Microsporidia. This analysis illuminates
      fundamentally different evolutionary paths and host interplay of specialist and
      generalist pathogens. 

PMID- 25968467
TI  - Dissecting blue light signal transduction pathway in leaf epidermis using a
      pharmacological approach.
AB  - MAIN CONCLUSION: Blue light signalling pathway in broad bean leaf epidermal cells
      includes key membrane transporters: plasma- and endomembrane channels and pumps
      of H (+) , Ca (2+) and K (+) ions, and plasma membrane redox system. Blue light
      signalling pathway in epidermal tissue isolated from the abaxial side of fully
      developed Vicia faba leaves was dissected by measuring the effect of inhibitors
      of second messengers on net K(+), Ca(2+) and H(+) fluxes using non-invasive ion
      selective microelectrodes (the MIFE system). Switching the blue light on-off
      caused transient changes of the ion fluxes. The effects of seven groups of
      inhibitors were tested in this study: CaM antagonists, ATPase inhibitors, Ca(2+)
      anatagonists or chelators, agents affecting IP3 formation, redox system
      inhibitors, inhibitors of endomembrane Ca(2+) transport systems and an inhibitor
      of plasma membrane Ca(2+)-permeable channels. Most of the inhibitors had a
      significant effect on steady-state (basal) net fluxes, as well as on the
      magnitude of the transient ion flux responses to blue light fluctuations. The
      data presented in this study suggest that redox signalling and, specifically,
      plasma membrane NADPH oxidase and coupled Ca(2+) and K(+) fluxes play an
      essential role in blue light signal transduction.

PMID- 25968468
TI  - Two cases of lung herniation treated by surgery or observation.
AB  - Lung herniation is rare. We describe two cases; one cured by surgery, and the
      other observed without surgery. A 61-year-old man underwent minimally invasive
      cardiac surgery for mitral valve plasty. Four weeks postoperatively, chest
      computed tomography (CT) revealed exacerbating lung herniation and emergency
      surgery was performed. A 75-year-old man with metastatic tumor underwent partial
      resection of the left lower lobe through a 10-cm access window. Three months
      postoperatively, follow-up chest CT revealed prolapse of a small part of the
      upper lobe at the site of incision. However, he remained asymptomatic and was
      observed on an outpatient basis. 

PMID- 25968469
TI  - Aortic root replacement for annuloaortic ectasia with a single coronary artery.
AB  - A single coronary artery, arising from the left sinus of Valsalva, associated
      with a bicuspid aortic valve and annuloaortic ectasia, is very rare. We report on
      a surgical case of bicuspid aortic valve regurgitation, annuloaortic ectasia, and
      dilation of the ascending aorta to the aortic arch in a patient with a single
      coronary artery. We successfully performed aortic root replacement with
      reimplantation of the single coronary artery and total arch replacement. The
      reimplantation of the coronary orifice required particular attention.
      Postoperative CT demonstrated the expected contours from the aortic annulus to
      the aortic arch with a patent implanted coronary artery.

PMID- 25968470
TI  - Effects of Endurance and Endurance Strength Training on Body Composition and
      Physical Capacity in Women with Abdominal Obesity.
AB  - AIMS: To compare the effects of endurance training with endurance strength
      training on the anthropometric, body composition, physical capacity, and
      circulatory parameters in obese women. METHODS: 44 women with abdominal obesity
      were randomized into groups A and B, and asked to perform endurance (A) and
      endurance strength training (B) for 3 months, 3 times/week, for 60 min. Dual
      energy X-ray absorptiometry and Graded Exercise Test were performed before and
      after training. RESULTS: Significant decreases in body mass, BMI, total body fat,
      total body fat mass, and waist and hip circumference were observed after both
      types of intervention. Marked increases in total body lean and total body fat
      free mass were documented in group B. In both groups, significant increases in
      peak oxygen uptake, time to exhaustion, maximal work rate, and work rate at
      ventilatory threshold were accompanied by noticeably decreased resting heart
      rate, resting systolic blood pressure, and resting and exercise diastolic blood
      pressure. No significant differences were noticed between groups for the
      investigated parameters. CONCLUSION: Our findings demonstrate evidence for a
      favorable and comparable effect of 3-month endurance and endurance strength
      training on anthropometric parameters, body composition, physical capacity, and
      circulatory system function in women with abdominal obesity.

PMID- 25968471
TI  - Sublobar Resection, Radiofrequency Ablation or Radiotherapy in Stage I Non-Small
      Cell Lung Cancer.
AB  - BACKGROUND: The best therapy for patients with stage I non-small cell lung cancer
      (NSCLC) who are medically unfit for lobectomy or prefer not to undergo surgery
      has not yet been demonstrated. OBJECTIVES: We analyzed data from our prospective
      database to evaluate the recurrence and survival rates and assess the extent to
      which the type of treatment explains outcome differences. METHODS: This study
      included 116 patients with histologically proven clinical stage I NSCLC who were
      treated with sublobar resection (SLR; n = 42), radiofrequency ablation (RFA; n =
      25) or radiotherapy (RT; n = 49) between 2009 and 2013. The primary end point was
      the time to primary tumor recurrence (PR). Kaplan-Meier curves and Cox regression
      were used to compare the recurrence patterns and survivals after adjustments for
      potential confounders. RESULTS: The SLR patients were younger and exhibited
      better performance status. The RT patients had larger tumors. After adjusting for
      age and tumor size, there were differences between the different treatments in
      terms of the PR rate, but no differences were observed in overall (OS) or disease
      free survival. The hazard ratio for PR comparing SLR versus RT adjusted for age
      and tumor size was 2.73 (95% confidence interval, CI, 0.72-10.27) and that for
      SLR versus RFA was 7.57 (95% CI 1.94-29.47). CONCLUSIONS: Our study suggests that
      SLR was associated with a higher primary tumor control rate compared to RFA or
      RT, although the OSs were not different. These results should be confirmed in
      prospective trials.

PMID- 25968472
TI  - Reticulocyte Hemoglobin Content During the First Month of Life in Critically Ill
      Very Low Birth Weight Neonates Differs From Term Infants, Children, and Adults.
AB  - BACKGROUND: Reticulocyte hemoglobin content (RET-He)-an established indicator of
      iron status in children and adults-was determined in very low birth weight (VLBW)
      infants. METHODS: Longitudinal retrospective RET-He data in 26 VLBW neonates
      during the first month of age were compared with: (a) concurrent complete blood
      counts (CBCs), including hemoglobin (Hb) concentration, reticulocyte count, and
      immature reticulocyte fraction (IRF), and erythropoietin (EPO) levels; (b)
      clinical variables; and (c) RET-He data from the literature for term infants,
      children, and adults. RESULTS: RET-He within 24 hr following birth was 31.8 +/-
      1.1 pg (mean +/- SEM). This was followed by an abrupt, significant decline to
      28.3 +/- 1.1 pg at 2-4 days, and to steady state levels of 28.4 +/- 0.5 pg
      thereafter. The changes in RET-He were mirrored by changes in plasma EPO,
      reticulocyte count, and IRF, but not Hb. Steady state RET-He values after 4 days
      were significantly lower than RET-He values for term infants, children, and
      adults (31.6 +/- 0.11, 32.0 +/- 0.12, and 33.0 +/- 0.13 pg, respectively).
      CONCLUSION: Although RET-He values in VLBW infant were lower than term infants,
      children, and adults, the significance and mechanism(s) responsible are unknown.
      The present VLBW infant data are relevant to investigations assessing
      hemoglobinization following treatment with recombinant human EPO (r-HuEPO) and/or
      iron.

PMID- 25968473
TI  - Development of a novel IGRA assay to test T cell responsiveness to HBV antigens
      in whole blood of chronic Hepatitis B patients.
AB  - BACKGROUND: Interferon gamma release assays (IGRA) have been developed to support
      easy and fast diagnosis of diseases like tuberculosis, and CMV in transplant
      patients. IGRAs focus on cellular immunity especially memory T cells and thus
      also allow rapid screening prior to complex flow cytometric testing. Here, we
      describe a novel, sensitive whole blood based cytokine release assay capable of
      assessing T cell responsiveness to HBV antigens in Hepatitis B patients and
      assessing hepatitis B vaccination status in healthy individuals. METHODS: Seventy
      two chronic Hepatitis B patients (CHB), 8 acute hepatitis B patients (AHB) and 80
      healthy controls (HC) were tested by ELISA for IFNgamma- and IL2-secretion in
      whole blood after challenge with synthetic peptide libraries of hepatitis B core
      antigen (HBcAg) or hepatitis B surface antigen (HBsAg). RESULTS: The developed
      IGRA test reliably differentiated between Hepatitis B patients, vaccinees and
      unvaccinated healthy controls. Treatment naive and treated CHB patients showed a
      weaker IFNgamma response to HBcAg (16 +/- 5 and 35 +/- 28 pg/ml, respectively)
      compared to the AHB group (82 +/- 39 pg/ml), whereas HC remained unresponsive (6
      +/- 1 pg/ml). IL2 levels after HBcAg challenge were also higher in the AHB group
      compared to naive and treated CHB as well as HC (47 +/- 21 vs. 12 +/- 3, 15 +/-
      10 and 12 +/- 9 pg/ml, respectively). HBsAg stimulation led to increased IFNgamma
      and IL2 levels in the AHB group (33 +/- 12 and 22 +/- 12 pg/ml) and even higher
      levels in HC due to a high hepatitis B vaccination rate (41 +/- 10 and 167 +/- 58
      pg/ml). Naive and treated CHB patients developed no or only weaker IFNgamma or
      IL2 responses to HBsAg (5 +/- 2 and 12 +/- 7 pg/ml, for naive CHB, 12 +/- 10 and
      18 +/- 15 pg/ml, for treated CHB). For HC, IL2 release after HBsAg stimulation
      depicted hepatitis B vaccination status with a diagnostic sensitivity and
      specificity of 85 % and 90 %. CONCLUSION: Our novel whole blood based cytokine
      release assay constitutes an easy and robust tool for screening HBV specific
      cellular immunity as alternative to flow cytometry or ELISPOT assays.

PMID- 25968474
TI  - Copper-catalyzed intermolecular asymmetric propargylic dearomatization of
      indoles.
AB  - The first copper-catalyzed intermolecular dearomatization of indoles by an
      asymmetric propargylic substitution reaction was developed. This method provides
      a highly efficient synthesis of versatile furoindoline and pyrroloindoline
      derivatives containing a quaternary carbon stereogenic center and a terminal
      alkyne moiety with up to 86 % yield and 98 % ee. 

PMID- 25968475
TI  - CT-Guided Percutaneous Transthoracic Needle Biopsies Using 10G Large-Core
      Needles: Initial Experience.
AB  - PURPOSE: Using large-core biopsy needles in CT-guided percutaneous transthoracic
      needle biopsies (PTNB) may be advantageous in terms of larger specimens, which
      facilitate more extensive histopathological, immunohistochemical, and molecular
      examination of tumor tissue. The aim of this study was to evaluate the success
      rate and safety in CT-guided PTNB using 10G large-core biopsy needles. METHODS
      AND MATERIALS: 35 patients with intrathoracic lesions suspected of malignancy
      underwent CT-guided PTNB using dedicated large-core biopsy needles (10G
      SpirotomeTM, Medinvents, Hasselt, Belgium). Location, tumor size, number of
      pleural passes, number of biopsies, histologic result, and complications
      (pneumothorax, bleeding) were recorded. RESULTS: Lesion location varied from
      pleural to hilar location. Mean tumor size was 3.5 cm (range 0.7-9.2 cm). Only
      one pleural passage was necessary in all patients. Mean distance from the pleura
      to the lesion was 2.6 cm (max 9.2 cm). Large-core biopsy (10G) was successful in
      88.6%. Pneumothorax was found in 40%. Minor intraparenchymal bleeding was present
      in 14 patients. No major complications were recorded. CONCLUSION: Large-core
      biopsy with 10G did not show higher complication rates compared to literature. It
      is technically feasible and safe. The obtained larger specimens may especially be
      helpful for the increasing demands of extensive molecular analysis for stratified
      patient care.

PMID- 25968476
TI  - Percutaneous Closure in Transfemoral Aortic Valve Implantation: A Single-Centre
      Experience.
AB  - PURPOSE: To report the experience of a percutaneous closure device used for
      transfemoral transcatheter aortic valve implantation (TAVI) in an unselected
      patient and operator population. MATERIALS AND METHODS: Eighty-two consecutive
      patients (32 women, 50 men) who underwent transfemoral TAVI between September
      2009 and February 2014 at our hospital were retrospectively reviewed for
      percutaneous closure device (PCD) failure, vascular complications, and bleeding.
      The diameter and calcification of the common femoral artery (CFA) and the
      thickness of the subcutaneous fat layer in the groin were assessed on computed
      tomography images. RESULTS: The incidences of PCD failure and minor and major
      vascular complications were 19.5% (n = 16/82), 19.5% (n = 16/82), and 7% (n =
      6/82) respectively. 8.5% (n = 7/82) had a minor perioperative bleeding, 6% (n =
      5/82) had a major bleeding, and none had any life-threatening bleeding. When PCD
      failed, haemostasis was obtained with fascia suturing, covered stent placement,
      or with surgical cutdown. Thirty-day mortality and 1-year all-cause mortality
      were 8.5% (n = 7/82) and 19.5% (n = 16/82), respectively. In a multiple
      regression analysis, the CFA diameter and the presence of severe calcification
      were independently related to PCD failure (correlation coefficient = -0.24, p =
      0.027 and correlation coefficient = 0.23, p = 0.036, respectively). CONCLUSION:
      PCD failure was related to a small CFA diameter and to a severely calcified CFA.
      Failure could largely be managed with minimally invasive techniques such as
      covered stents or fascia suturing.

PMID- 25968477
TI  - Is seven the minimum number of water molecules per ion pair for assured
      biological activity in ionic liquid-water mixtures?
AB  - Ionic liquids (ILs) containing small amounts of water are called hydrated ILs and
      they show diverse physico-chemical properties that are strongly dependent on
      their water content. Some properties of hydrated ILs, such as biological activity
      and phase transition behaviour, were found to change non-linearly, with an
      inflection at a water molecule to ion pair ratio of around 7:1. This critical
      hydration number of ILs has been discussed in this paper with respect to the
      state of solvated water molecules.

PMID- 25968478
TI  - Acupoint Specificity on Colorectal Hypersensitivity Alleviated by Acupuncture and
      the Correlation with the Brain-Gut Axis.
AB  - This project was focused on the study of the effect of the different acupoints on
      visceral hypersensitivity and the correlation with the brain-gut axis. By using a
      mouse model of zymosan-induced colorectal hypersensitivity, and observing the
      response of hypersensitivity model to colorectal distension stimulation in
      acupuncture at different acupoints, we selected the specific acupoints. With
      immunohistochemical staining method, we observed c-fos expression, distribution
      and changes after acupuncture on sensory pathway, including colorectum, spinal
      dorsal horn and different regions of brain center in the model with colorectal
      distension stimulation, and evaluated the acupuncture effect on brain-gut axis.
      The results revealed that the effectiveness of acupuncture for alleviating
      visceral hypersensitivity was different at individual acupoint, meaning Tianshu
      (ST25), Zusanli (ST36) and Shangjuxu (ST37) > Quchi (LI11) and Dachangshu (BL25)
      > Ciliao (BL32). C-fos expression was concentrated in anterior cingulate cortex,
      hypothalamus, spinal dorsal horn and colorectum in model of zymosan-induced
      colorectal hypersensitivity and it was down-regulated after acupuncture. The
      results demonstrates that the acupoint specificity presents in acupuncture for
      relieving visceral hypersensitivity and the effects are more predominated at the
      acupoints on stomach meridian innervated by the same or adjacent spinal ganglion
      segments. The model of zymosan-induced colorectal hypersensitivity can be the
      animal model simulating brain-gut interaction. 

PMID- 25968479
TI  - fDWI Evaluation of Hypothalamic Appetite Regulation Pathways in Mice Genetically
      Deficient in Leptin or Neuropeptide Y.
AB  - We evaluate the contribution of leptin-dependent anorexigenic pathways and
      neuropeptide Y (NPY)-dependent orexigenic pathways to the changes in hypothalamic
      water diffusion parameters observed in vivo by functional diffusion weighted MRI
      (fDWI). Mice genetically deficient in leptin (B6.V-Lep (ob) /J) or NPY (129S-Npy
      (tm1Rpa) /J) and the corresponding wild-type controls, were subjected to
      sequential isocaloric feeding, fasting and recovery regimes. Non-invasive fDWI
      measurements were performed under these conditions, and complemented with
      parallel determinations of food and water consumption, respiratory exchange ratio
      (RER), locomotor activity and endocrine profiles. Control mice showed significant
      increases in hypothalamic water diffusion parameters upon fasting, returning to
      normal values in the recovery period. Leptin deficient mice depicted permanently
      increased water diffusion parameters under all feeding conditions as compared to
      wild type controls, without important changes upon fasting or recovery. These
      results paralleled sustained increases in food and water intake, significantly
      augmented body weight, and decreased RER values or locomotor activity, thus
      configuring an obese phenotype. NPY-deficient mice showed significantly reduced
      increases (or even slight decreases) in the water diffusion parameters upon
      fasting as compared to wild type controls, paralleled by decreased food and water
      intake during the recovery period. In conclusion, leptin deficiency results in
      sustained orexigenic stimulation, leading to increased water diffusion
      parameters, while NPY deficiency lead to reduced orexigenic stimulation and water
      diffusion parameters. Diffusion changes are proposed to reflect net astrocytic
      volume changes induced by the balance between the orexigenic and anorexigenic
      firings of AgRP/NPY and POMC/CART neurons, respectively. Together, our results
      suggest that fDWI provides an adequate tool to investigate hypothalamic appetite
      disorders. 

PMID- 25968481
TI  - Flow and mixing by small intestine villi.
AB  - Flow and mixing in the small intestine are multi-scale processes. Flows at the
      scale of the villi (finger-like structures of ~500 MUm length) are poorly
      understood. We developed a three-dimensional lattice-Boltzmann model to gain
      insight into the effects of villous movements and the rheology of digesta on
      flow, mixing and absorption of nutrients at the periphery of the intestinal
      lumen. Our model simulated the hydrodynamic consequences of villi movements that
      resulted from folding of the mucosa during longitudinal contractions. We found
      that cyclic approximation and separation of groups of villi generated laminar
      eddies at the edges of the group and augmented mass transfers in the radial
      direction between the inter-villous space and the intestinal lumen which improved
      the absorption of nutrients and mixing at the periphery of the lumen. This
      augmentation was greater with highly diffusible nutrients and with high levels of
      shear-thinning (pseudoplasticity) of the fluid. We compared our results with bulk
      flows simulations done by previous workers and concluded that villous movements
      during longitudinal contractions is a major radial mixing mechanism in the small
      intestine and increases mixing and absorption around the mucosa despite adverse
      rheology.

PMID- 25968480
TI  - Mitochondrial Division Inhibitor 1 Ameliorates Mitochondrial Injury, Apoptosis,
      and Motor Dysfunction After Acute Spinal Cord Injury in Rats.
AB  - Mitochondrial division inhibitor 1 (Mdivi-1) is the most effective
      pharmacological inhibitor of mitochondrial fission. Spinal cord injury (SCI) is a
      common and serious trauma, which lacks efficient treatment. This study aimed to
      detect the role of Mdivi-1 in neuronal injury and its underlying mechanism after
      acute SCI (ASCI) in rats. Western blot analysis showed that Bax levels on the
      mitochondrial outer membrane, and release of cytochrome C (cytC) and apoptosis
      inducing factor (AIF) from the mitochondria began to increase significantly at 4
      h after ASCI, then peaked at 16 h, and declined significantly from 16 to 24 h.
      However, the mitochondrial levels of Bcl-2 increased significantly at 2 h, peaked
      at 4 h, and subsequently significantly decreased from 4 to 24 h after ASCI. In
      addition, Mdivi-1(1.2 mg/kg) significantly suppressed the translocation of
      dynamin-related protein 1 (Drp1) and Bax to the mitochondria, mitochondrial
      depolarization, decrease of ATP and reduced Glutathione, increase of the
      Malondialdehyde, cytC release, and AIF translocation at 16 h and 3 days after
      ASCI, and also inhibited the caspase-3 activation and decrease of the percentage
      of apoptotic cells at 16 h, 3 and 10 days, further, ameliorated the motor
      dysfunction greatly from 3 to 10 days after ASCI in rats. This neuroprotective
      effect was dose-dependent. However, Mdivi-1(1.2 mg/kg) had no effects on the
      translocation of Bcl-2 and fission protein 1 on the mitochondria, and did not
      affect the expression of total Drp1 at 16 h after ASCI. Our experimental findings
      indicated that Mdivi-1 can protect rats against ASCI, and that its underlying
      mechanism may be associated with inhibition of Drp1 translocation to the
      mitochondria, alleviation of mitochondrial dysfunction and oxidative stress, and
      suppression of caspase-dependent and -independent apoptosis. 

PMID- 25968482
TI  - Real-world determinants of adjunctive antipsychotic prescribing for patients with
      major depressive disorder and inadequate response to antidepressants: a case
      review study.
AB  - INTRODUCTION: Patients with major depressive disorder (MDD) often fail to respond
      to first-line antidepressant treatments (ADTs); subsequent strategies include
      dosage increase, switch to a different ADT, or addition of another ADT or other
      drug. The objective of this prospective, case review study was to identify
      factors that influence the decision to prescribe adjunctive antipsychotics for
      patients with MDD and inadequate response to ADT. METHODS: Psychiatrists or
      primary care physicians (n=411) based in the USA and Europe each completed an
      online survey for ten consecutive adults with MDD and inadequate response to
      ADTs, and for whom a treatment change was considered. A t test was used to
      compare survey responses between groups of patients. RESULTS: The survey was
      completed for 4018 patients; an adjunctive antipsychotic was considered for
      961/4018 patients (23.9%) and actually prescribed for 514/4018 (12.8%). Compared
      with patients not considered for an adjunctive antipsychotic, those who were
      considered for this treatment had more previous major depressive episodes (MDEs),
      longer duration of the current MDE, more severe illness both at ADT initiation
      and current consultation, and more treatment changes. Patients who were
      prescribed adjunctive antipsychotics had at baseline more functional impairment
      and absences from work than those considered for but not prescribed this
      treatment. Key symptoms that prompted physicians to consider antipsychotics were
      psychotic symptoms, psychomotor agitation, hostility, irritability, impulsivity,
      and anger bursts. Anxious mood and irritability were mentioned significantly more
      often by physicians who actually prescribed adjunctive antipsychotics. Obstacles
      to prescribing included a tendency to wait to see if symptoms improved and
      concern over side effects. CONCLUSION: This real-world study suggested that the
      decision to prescribe an adjunctive antipsychotic for patients with MDD and
      inadequate response to ADT is influenced by a broad spectrum of factors,
      predominantly related to severity of illness, functional impairment, and symptom
      profile. FUNDING: Otsuka Pharmaceutical Development & Commercialization, Inc.
      (Princeton, USA) and H. Lundbeck A/S (Valby, Denmark).

PMID- 25968483
TI  - Atovaquone for Prophylaxis of Toxoplasmosis after Allogeneic Hematopoietic Stem
      Cell Transplantation.
AB  - Toxoplasmosis and infections by other opportunistic agents such as Pneumocystis
      jirovecii constitute life-threatening risks for patients after allogeneic
      hematopoietic stem cell transplantation. Trimethoprim/sulfamethoxazole (TMP-SMX)
      has been well established for post-transplant toxoplasmosis and pneumocystis
      prophylaxis, but treatment may be limited due to toxicity. We explored atovaquone
      as an alternative and compared it with TMP-SMX regarding toxicity and efficacy
      during the first 100 days after transplantation in 155 consecutive adult stem
      cell recipients. Eight patients with a prior history of TMP-SMX intolerance
      received atovaquone as first-line prophylaxis. TMP-SMX was used for 141 patients
      as first-line strategy, but 13 patients (9.2%) were later switched to atovaquone
      due to TMP-SMX toxicity or gastrointestinal symptoms. No active toxoplasmosis or
      active P. jirovecii infection developed under continued prophylaxis with either
      TMP-SMX or atovaquone. However, for reasons of TMP-SMX and/or atovaquone
      toxicity, 7 patients were unable to tolerate any efficacious toxoplasmosis
      prophylaxis and therefore obtained inhalative pentamidine as P. jirovecii
      prophylaxis but no toxoplasmosis prophylaxis. Importantly, 2 of these patients
      developed severe toxoplasmosis. In summary, atovaquone appears as a valid
      alternative for at least some post-transplant patients who cannot tolerate TMP
      SMX. This should be further confirmed by multicenter trials. 

PMID- 25968484
TI  - Development of a single vial kit formulation of [99mTc]-labeled doxorubicin for
      tumor imaging and treatment response assessment-preclinical evaluation and
      preliminary human results.
AB  - The present study describes the successful radiolabeling of [99mTcO(-) 4 ] with
      doxorubicin, and the resultant product was formulated in to a ready-to-label
      lyophilized single vial kit preparation for convenient use in a routine clinical
      setting. The radiolabeled preparation of [99mTc]-doxorubicin exhibited a high
      radiolabeling efficiency of more than 95.0%, serum stability for up to 24 h, and
      shelf-life of lyophilized cold kits was more than 6 months. Animal imaging data
      in tumor-bearing mice demonstrated that [99mTc]-doxorubicin accumulated in the
      tumor site with high target (tumor) to non-target (contra-lateral thigh) ratio
      (3.2 +/- 0.5). The ratio decreased to 1.2 +/- 0.6 indicating a good response on
      follow up imaging performed after 2 weeks of doxorubicin treatment. [99mTc]
      doxorubicin scintigraphic data in human volunteers supported the hepato-renal
      excretion of the radiotracer as reflected by the increased accumulation of the
      radiotracer as a function of time in intestine, kidneys, and urinary bladder.
      Further, imaging in patients (very limited number) indicated that the technique
      may be useful in the detection of active sarcoma and post treatment
      (surgery/chemotherapy) remission or absence of the disease. The technique,
      however, needs validation through further preclinical evaluation and imaging in a
      larger number of patients. 

PMID- 25968485
TI  - Rates and effectiveness of antiviral use among hospitalized influenza patients.
AB  - The influenza virus is currently a global public health problem. There are
      several thousand cases of classic and newly emerging atypical influenza virus
      infections around the world annually. Prevention, early diagnosis and treatment
      are the keys to managing influenza outbreaks. Some influenza treatments have
      proven to be more useful than others. A standard antiviral drug has been
      developed and is recommended for the management of hospitalized influenza
      patients. This article briefly outlines the rates and effectiveness of antiviral
      use among hospitalized influenza patients. It also discusses some important
      considerations regarding controversial issues and future perspectives on
      antiviral use for the management of hospitalized influenza patients. 

PMID- 25968487
TI  - The effect of intravesical chemotherapy in the prevention of intravesical
      recurrence after nephroureterectomy for upper tract urothelial carcinoma: a meta
      analysis.
AB  - CONTEXT: The standard management of upper urinary tract urothelial carcinoma (UUT
      UC) is nephroureterectomy with bladder cuff excision, but after surgery,
      approximately 22-47% of patients with UUT-UC develop subsequent bladder tumour
      recurrence, potentially because of the implantation of cancer cells from the
      primary tumour. OBJECTIVE: To conduct a meta-analysis to evaluate the effect of
      prophylactic intravesical chemotherapy in the prevention of bladder recurrence
      after nephroureterectomy for UUT-UC. DATA ACQUISITION: An electronic database
      search of Medline, Embase, the Cochrane Library, CancerLit and ClinicalTrials.gov
      was performed to identify appropriate studies prior to March 2013.All studies
      comparing nephroureterectomy alone with prophylactic intravesical chemotherapy
      after nephroureterectomy were included. The main outcome measure for this meta
      analysis was the rate of bladder recurrence after nephroureterectomy. The search
      was not limited by language. The review process followed the guidelines of the
      Cochrane Collaboration. The analysis was conducted using the Review Manager
      Version RevMan 5.0 software (The Nordic Cochrane Centre, The Cochrane
      Collaboration). RESULTS: A total of 592 patients were included in this study, of
      whom 257 underwent intravesical instillation after nephroureterectomy and 335
      underwent nephroureterectomy alone. Our meta-analysis demonstrated that the rate
      of recurrence after 12 months was significantly lower in the intravesical
      instillation after nephroureterectomy group than in the nephroureterectomy-alone
      group [odds ratio (OR): 0.48; 95% confidence interval (CI): 0.28-0.81; P =
      0.006]. A significant decrease in bladder recurrence after at least 24  months
      was also observed in the intravesical instillation after nephroureterectomy group
      (OR: 0.40; 95% CI: 0.24-0.67; P = 0.0004). A subgroup analysis demonstrated that
      the pattern of differences was similar to those from the total group analysis.
      CONCLUSIONS: Prophylactic intravesical chemotherapy was effective for the
      prevention of bladder recurrence after nephroureterectomy. Therefore, we suggest
      that prophylactic intravesical chemotherapy should be performed in patients with
      UUT-UC after nephroureterectomy, but the optimal chemotherapy regimen and the
      initial time of instillation should be explored in future studies.

PMID- 25968488
TI  - Laparoscopic cholecystectomy in pregnancy: An Australian retrospective cohort
      study.
AB  - INTRODUCTION: Biliary tract disease is a common non-obstetric surgical
      presentation during pregnancy. Although small international series demonstrate
      favourable outcomes following laparoscopic cholecystectomy (LC) during pregnancy,
      there is a paucity of Australian data to complement these findings. METHOD:
      Between 1st January 2003 and 30th June 2013, all patients undergoing planned LC
      during pregnancy at Western Health were retrospectively identified. RESULTS:
      Twenty-two patients underwent planned LC with 3 (13%) cases converted to open
      surgery. The median maternal age was 31 years (27.8-36) with an estimated median
      gestational age (EGA) of 19.5 weeks (16.5-23.5). Eighteen (82%) cases were
      performed during the second trimester. Nine (40%) patients had 2 or more hospital
      admissions for similar presentations. Twelve (54%) were performed as index cases.
      Operative indications included 12 (54%) with recurrent biliary colic, five (22%)
      with acute cholecystitis and 3 (14%) with gallstone pancreatitis. Median
      operating time for completed LCs was 65 min (60-95). Intra-operative
      cholangiogram was performed in seven (32%) cases, 5 (71%) of which employed
      protective uterine lead shielding. There was no fetal loss or uterine injury.
      Median hospital stay was 3 days (2-7) for completed LCs. Major morbidity occurred
      in 2 (10%) completed LCs that required a return to theatre. Five (23%) births
      were lost to follow up. The median time to delivery post-surgery was 13 weeks (11
      15). Two (12%) preterm deliveries occurred, with subsequent neonatal
      complications. CONCLUSION: Antenatal laparoscopic cholecystectomy demonstrated
      comparably safe outcomes. Increasing its utilization to manage symptomatic
      cholelithiasis during pregnancy may be considered.

PMID- 25968489
TI  - Lessons learned from integrating simultaneous triple point-of-care screening for
      syphilis, hepatitis B, and HIV in prenatal services through rural outreach teams
      in Guatemala.
AB  - Mother-to-child-transmission of HIV, syphilis, and hepatitis B virus (HBV)
      remains a challenge in Guatemala, especially in rural regions. A triple antenatal
      screening program for these infections using point-of-care (POC) testing offered
      through outreach teams was implemented in the municipality of Puerto de San Jose.
      One year following program implementation, antenatal care coverage increased to
      99.6% (32.5% increase, P<0.001), testing uptake increased to 50.3% for HIV and
      syphilis (143.9% (P<0.001) and 1.3% (P=0.89) increase, respectively), and HBV
      testing increased from 0 to 42.2%. Lessons learned showed that, despite the
      expansion of triple antenatal POC screening in rural Guatemala, a shortage of
      healthcare workers and poor supply chain management limited screening uptake.
      Moreover, training is essential to help health workers overcome their fear of
      communicating positive results and improve partner notification. Engagement of
      community health workers was essential to build local capacity and facilitate
      community acceptance. 

PMID- 25968490
TI  - Prevention of mother-to-child transmission of syphilis and HIV in China: What
      drives political prioritization and what can this tell us about promoting dual
      elimination?
AB  - OBJECTIVE: The present study aims to identify reasons behind the lower political
      priority of mother-to-child transmission (MTCT) of syphilis compared with HIV,
      despite the former presenting a much larger and growing burden than the latter,
      in China, over the 20years prior to 2010. METHODS: We undertook a comparative
      policy analysis, based on informant interviews and documentation review of
      control of MTCT of syphilis and HIV, as well as nonparticipant observation of
      relevant meetings/trainings to investigate agenda-setting prior to 2010. RESULTS:
      We identified several factors contributing to the lower priority accorded to MTCT
      of syphilis: relative neglect at a global level, dearth of international
      financial and technical support, poorly unified national policy community with
      weak accountability mechanisms, insufficient understanding of the epidemic and
      policy options, and a prevailing negative framing of syphilis that resulted in
      significant stigmatization. CONCLUSION: A dual elimination goal will only be
      reached when prioritization of MTCT of syphilis is enhanced in both the
      international and national agendas.

PMID- 25968491
TI  - Uterine arterial embolization to assist induction of labor among patients with
      complete placenta previa.
AB  - OBJECTIVE: To investigate labor induction after uterine arterial embolization
      (UAE) among patients with complete placenta previa (CPP). METHODS: A prospective
      study was conducted of women with a singleton pregnancy (16-35 weeks) and CPP
      admitted to a center in Changsha, China, for induction of labor because of a
      fetal anomaly between March 2009 and December 2013. Patients underwent
      intervention-assisted labor induction (IALI) with UAE, or cesarean delivery. A
      control group of 30 women without CPP but undergoing labor induction was also
      enrolled. Hemoglobin levels, postpartum blood loss, and length of labor were
      assessed. RESULTS: Mean postpartum blood loss was lower in the IALI group (n=32;
      301.25+/-128.07 mL) than in the cesarean group (n=15; 693.33+/-244.85 mL;
      P=0.049), but was not different from that in the control group (143.50+/-16.06
      mL; P=0.325). The reduction in mean hemoglobin level was significantly lower in
      the IALI group (-6.53+/-2.20 g/L) than in the cesarean group (-8.40+/-2.17g/L;
      P=0.005), but higher than in the control group (-0.20+/-0.35 g/L; P=0.007).
      Duration of labor did not differ between the IALI and control groups (8.70+/-2.32
      vs 4.76+/-0.47 hours; P=0.108). CONCLUSION: UAE to assist induction of labor
      could be considered a feasible option for patients with CPP.

PMID- 25968492
TI  - Assessment of the impact of rapid syphilis tests on syphilis screening and
      treatment of pregnant women in Zambia.
AB  - OBJECTIVE: To evaluate the impact of rapid syphilis tests (RSTs) on syphilis
      testing and treatment in pregnant women in Kalomo District, Zambia. METHODS: In
      March 2012, health workers at all 35 health facilities in Kalomo Distract were
      trained in RST use and penicillin treatment. In March 2013, data were
      retrospectively abstracted from 18 randomly selected health facilities and
      stratified into three time intervals: baseline (6months prior to RST
      introduction), midline (0-6 months after RST introduction), and endline (7-12
      months after RST introduction). RESULTS: Data collected on 4154 pregnant women
      showed a syphilis-reactive seroprevalence of 2.7%. The proportion of women
      screened improved from baseline (140/1365, 10.6%) to midline (976/1446, 67.5%),
      finally decreasing at endline (752/1337, 56.3%) (P<0.001). There was no
      significant difference in the proportion of syphilis-seroreactive pregnant women
      who received 1 dose of penicillin before (1/2, 50%) or after (5/48, 10.4%;
      P=0.199) RST introduction with low treatment rates throughout. CONCLUSION: With
      RST scale-up in Zambia and other resource-limited settings, same-day test and
      treatment with penicillin should be prioritized to achieve the goal of
      eliminating congenital syphilis.

PMID- 25968493
TI  - Quantitative inferences on the locomotor behaviour of extinct species applied to
      Simocyon batalleri (Ailuridae, Late Miocene, Spain).
AB  - Inferences of function and ecology in extinct taxa have long been a subject of
      interest because it is fundamental to understand the evolutionary history of
      species. In this study, we use a quantitative approach to investigate the
      locomotor behaviour of Simocyon batalleri, a key taxon related to the ailurid
      family. To do so, we use 3D surface geometric morphometric approaches on the
      three long bones of the forelimb of an extant reference sample. Next, we test the
      locomotor strategy of S. batalleri using a leave-one-out cross-validated linear
      discriminant analysis. Our results show that S. batalleri is included in the
      morphospace of the living species of musteloids. However, each bone of the
      forelimb appears to show a different functional signal suggesting that inferring
      the lifestyle or locomotor behaviour of fossils can be difficult and dependent on
      the bone investigated. This highlights the importance of studying, where
      possible, a maximum of skeletal elements to be able to make robust inferences on
      the lifestyle of extinct species. Finally, our results suggest that S. batalleri
      may be more arboreal than previously suggested. 

PMID- 25968496
TI  - Design and simulation of an electrically pumped Schottky-junction-based plasmonic
      amplifier.
AB  - We have investigated an amplifier which operates on surface plasmon polaritons
      (SPPs). A semiconductor is considered instead of dielectric since its interface
      with metal can support transverse-magnetic-polarized SPP propagation. A T-shaped
      cross section for the analyzed waveguide is considered. Metal-semiconductor
      interface conditions in particular can be regarded as a Schottky junction that
      has the capability of being pumped electrically. So compensation of propagation
      loss imposed by metal is possible and beyond that, amplification occurs. This
      configuration has advantages such as a simple fabrication process and compact
      size. This scheme has been implemented previously in 3.16, 1.7, and 0.8 MUm for
      increasing the propagation length of the SPP but here, the free-space wavelength
      of 1.55 MUm is considered for designing a plasmonic amplifier. This wavelength is
      selected because this is the most used wavelength in fiber-optic
      telecommunications due to its ultralow attenuation in silica. However, designing
      such an amplifier with too many effects that arise in a Schottky junction may be
      an extremely difficult process. So simplification, which regards essential
      effects and ignores nonimportant ones, is included. In this work, gold is
      considered as the metal and n<sup>+</sup>-doped
      In<sub>0.53</sub>Ga<sub>0.47</sub>As as the semiconductor to form a Schottky
      junction. The semiconductor has a doping concentration of 1*10<sup>18</sup> 
      cm<sup>-3</sup>. In forward bias of 1.25 V, the gain coefficient of the SPP mode
      is estimated up to 337  cm<sup>-1</sup> which corresponds to 14.62 dB power gain
      for a 100 MUm long amplifier. 

PMID- 25968494
TI  - Synergistic activity of combination therapy with PEGylated pemetrexed and
      gemcitabine for an effective cancer treatment.
AB  - Combination therapy in cancer is now opted as a potential therapeutic strategy
      for cancer treatment. However, effective delivery of drugs in combination at the
      tumor site is marred by low bioavailability and systemic toxicity of individual
      drugs. Polymer therapeutics is indeed an upcoming approach for the combinational
      drug delivery in favor of better cancer management. Hence, the objective of our
      investigation was to develop a dual drug PEGylated system that carries two
      chemotherapeutic drugs simultaneously for effective treatment of cancer. In this
      regard, we have synthesized Pem-PEG-Gem, wherein pemetrexed (Pem) and gemcitabine
      (Gem) are conjugated to a heterobifunctional polyethylene glycol (PEG) polymer
      for the effective treatment of Non-Small Cell Lung Cancer (NSCLC). Our results
      demonstrate enhanced bioavailability of the individual drugs in Pem-PEG-Gem in
      comparison with the drugs in their native form. The developed Pem-PEG-Gem showed
      enhanced cell death with respect to their native counterparts when treated singly
      or in combination against NSCLC cells. This might be attributed to better
      cellular internalization through the process of macropinocytosis and synergistic
      cytotoxic action of Pem-PEG-Gem in NSCLC cells. Hence, we propose the above dual
      drug based polymer therapeutic approach suitable for better clinical application
      in the treatment of NSCLC. 

PMID- 25968497
TI  - 3D flame topography obtained by tomographic chemiluminescence with direct
      comparison to planar Mie scattering measurements.
AB  - This work reports the measurements of 3D flame topography using tomographic
      chemiluminescence and its validation by direct comparison against planar Mie
      scattering measurements. Tomographic measurements of the 3D topography of various
      well-controlled laboratory flames were performed using projections measured by
      seven cameras, and a simultaneous Mie scattering measurement was performed to
      measure a 2D cross section of the 3D flame topography. The tomographic
      measurements were based on chemiluminescence emissions from the flame, and the
      Mie scattering measurements were based on micrometer-size oil droplets seeded
      into the flow. The flame topography derived from the 3D tomographic and the Mie
      scattering measurement was then directly compared. The results show that the
      flame topography obtained from tomographic chemiluminescence and the Mie
      measurement agreed qualitatively (i.e., both methods yielded the same profile of
      the flame fronts), but a quantitative difference on the order of millimeters was
      observed between these two methods. These results are expected to be useful for
      understanding the capabilities and limitations of the 3D tomographic and Mie
      scattering techniques in combustion diagnostics. 

PMID- 25968495
TI  - Effect of Combining Ivabradine and beta-Blockers: Focus on the Use of Carvedilol
      in the SHIFT Population.
AB  - OBJECTIVES: We explored the prescription of beta-blockers with ivabradine in
      patients with systolic heart failure, focusing on the most frequently
      coprescribed beta-blocker, carvedilol. METHODS: We analyzed outcomes in SHIFT
      patients with systolic heart failure who were prescribed beta-blockers
      (carvedilol, bisoprolol, metoprolol, or nebivolol) with ivabradine or placebo.
      Analysis was by intention to treat in patients prescribed a beta-blocker at the
      time of the event. RESULTS: Data were available for 2,596 patients receiving
      carvedilol, 1,483 bisoprolol, 1,424 metoprolol, and 197 nebivolol. Mean treatment
      duration was 19 months. There was no difference in the effect of ivabradine on
      the primary composite endpoint of cardiovascular death or heart failure
      hospitalization between the various beta-blockers [hazard ratios (HR) for risk
      reduction, 0.75-0.89; p for interaction=0.86]. Patients prescribed carvedilol
      with ivabradine had lower rates of primary composite endpoint (HR 0.80, 95% CI:
      0.68-0.94), heart failure hospitalization (HR 0.73, 95% CI: 0.61-0.88), and
      cardiovascular hospitalization (HR 0.80, 95% CI: 0.69-0.92) versus carvedilol
      with placebo. The dosage of carvedilol had no detectable effect and there were no
      unexpected safety issues. CONCLUSIONS: Whatever beta-blocker was coprescribed
      with ivabradine, there were improvements in cardiovascular outcomes in patients
      with systolic heart failure, especially with the most prescribed beta-blocker-
      carvedilol.

PMID- 25968498
TI  - Optimal pseudorandom pulse position modulation ladar waveforms.
AB  - An algorithm for generating optimal pseudorandom pulse position modulation
      (PRPPM) waveforms for ladar ranging is presented. Bistatic ladar systems using
      Geiger-mode avalanche photodiodes require detection of several pulses in order to
      generate sufficient target statistics to satisfy some detection decision rule.
      For targets with large initial range uncertainty, it becomes convenient to
      transmit a pulse train with large ambiguity range. One solution is to employ a
      PRPPM waveform. An optimal PRPPM waveform will have minimal sidelobes: equivalent
      to 1 or 0 counts after the pulse correlation filter (compression). This can be
      accomplished by generating PRPPM pulse trains with optimal or minimal sidelobe
      autocorrelation. 

PMID- 25968499
TI  - Tunable filter using ferroelectric-dielectric periodic multilayer.
AB  - The microwave optical properties of a photonic crystal-based tunable single and
      multichannel filter are theoretically investigated using the transfer matrix
      method, finite difference time domain method, and the plane wave expansion
      method. By applying an external voltage of 8  V/micron about a 35% frequency
      tuning is obtained. It is found that the number of transmission peaks is directly
      proportional to the number of periods (N). In addition to this, the dependence of
      layer thicknesses, angle of incidence and polarization are also analyzed, and it
      is noticed that the filtering frequency is invariant in angle and polarization. 

PMID- 25968500
TI  - Multiple signal classification for self-mixing flowmetry.
AB  - For the first time to our knowledge, we apply the multiple signal classification
      (MUSIC) algorithm to signals obtained from a self-mixing flow sensor. We find
      that MUSIC accurately extracts the fluid velocity and exhibits a markedly better
      signal-to-noise ratio (SNR) than the commonly used fast Fourier transform (FFT)
      method. We compare the performance of the MUSIC and FFT methods for three decades
      of scatterer concentration and fluid velocities from 0.5 to 50 mm/s. MUSIC
      provided better linearity than the FFT and was able to accurately function over a
      wider range of algorithm parameters. MUSIC exhibited excellent linearity and SNR
      even at low scatterer concentration, at which the FFT's SNR decreased to
      impractical levels. This makes MUSIC a particularly attractive method for flow
      measurement systems with a low density of scatterers such as microfluidic and
      nanofluidic systems and blood flow in capillaries. 

PMID- 25968501
TI  - Nano-finishing of BK7 optical glass using magnetic abrasive finishing process.
AB  - BK7 is an optical glass extensively used in lens manufacturing. In this work,
      magnetic abrasive finishing (MAF) method was utilized for finishing of this hard
      to-machine material and the effect of various process parameters on surface
      roughness was investigated using response surface methodology. The best surface
      roughness value achieved was 23 nm. Among various finishing parameters, the
      abrasive size was found to be the most significant parameter followed by
      machining gap, magnetic particles size, rotational speed, and percentage weight
      of binding agent. Also, the mechanisms of material removal were studied by using
      atomic force microscopy (AFM). The AFM observations revealed that both
      microcutting and microfracture mechanisms might exist during MAF of brittle
      materials depending on the finishing conditions. 

PMID- 25968502
TI  - New miniaturized exhaled nitric oxide sensor based on a high Q/V mid-infrared 1D
      photonic crystal cavity.
AB  - A high Q/V mid-infrared 1D photonic crystal cavity in chalcogenide glass AMTIR-1
      (Ge<sub>33</sub>As<sub>12</sub>Se<sub>55</sub>) resonating at
      lambda<sub>R</sub>=5.26  MUm has been proposed as a key element of a sensor able
      to evaluate the nitric oxide (NO) concentration in the exhaled breath, namely
      fraction exhaled NO. The cavity design has been carried out through 3D finite
      element method simulations. A Q-factor of 1.1*10<sup>4</sup> and a mode volume
      V=0.8  (lambda/n)<sup>3</sup>, corresponding to a Q/V ratio of
      1.4*10<sup>4</sup>(lambda/n)<sup>-3</sup>, have been obtained with a resonance
      transmission coefficient T=15%. A sensitivity of 10 ppb has been calculated with
      reference to the photothermal physical property of the material. Such a result is
      lower than the state-of-the-art of NO sensors proposed in literature, where
      hundreds of parts per trillion-level detection seem to have been achieved, but
      comparable with the performance obtained by commercial devices. The main
      advantages of the new device are in terms of footprint (=150  MUm<sup>2</sup>),
      smaller at least 1 order of magnitude than those in literature, fast response
      time (only few seconds), and potential low cost. Such properties make possible in
      a handheld device the sensor integration in a multi-analysis system for detecting
      the presence of several trace gases, improving prevention, and reducing the
      duration of drug treatment for asthma and viral infections. 

PMID- 25968503
TI  - Maximum reflectance difference for incident p- and s-polarized light at air
      dielectric interfaces: erratum.

PMID- 25968504
TI  - Optical design for uniform scanning in MEMS-based 3D imaging lidar.
AB  - This paper proposes a method for the optical system design of uniform scanning in
      a larger scan field of view (FOV) in 3D imaging lidar. The theoretical formulas
      are derived for the design scheme. By employing the optical design software
      ZEMAX, a foldaway uniform scanning optical system based on MEMS has been
      designed, and the scanning uniformity and spot size of the system on the target
      plane, perpendicular to optical axis, are analyzed and discussed. Results show
      that the designed system can scan uniformly within the FOV of 40 degrees *40
      degrees  with small spot size for the target at distance of about 100 m. 

PMID- 25968505
TI  - Integrating optical fabrication and metrology into the optical design process.
AB  - The recent validation of a generalized linear systems formulation of surface
      scatter theory and an analysis of image degradation due to surface scatter in the
      presence of aberrations has provided credence to the development of a systems
      engineering analysis of image quality as degraded not only by diffraction effects
      and geometrical aberrations, but to scattering effects due to residual optical
      fabrication errors as well. This generalized surface scatter theory provides
      insight and understanding by characterizing surface scatter behavior with a
      surface transfer function closely related to the modulation transfer function of
      classical image formation theory. Incorporating the inherently band-limited
      relevant surface roughness into the surface scatter theory provides mathematical
      rigor into surface scatter analysis, and implementing a fast Fourier transform
      algorithm with logarithmically spaced data points facilitates the practical
      calculation of scatter behavior from surfaces with a large dynamic range of
      relevant spatial frequencies. These advances, combined with the continuing
      increase in computer speed, leave the optical design community in a position to
      routinely derive the optical fabrication tolerances necessary to satisfy specific
      image quality requirements during the design phase of a project; i.e., to
      integrate optical metrology and fabrication into the optical design process. 

PMID- 25968506
TI  - Wavelength modulation spectroscopy--digital detection of gas absorption harmonics
      based on Fourier analysis.
AB  - This work presents a detailed study of the theoretical aspects of the Fourier
      analysis method, which has been utilized for gas absorption harmonic detection in
      wavelength modulation spectroscopy (WMS). The lock-in detection of the harmonic
      signal is accomplished by studying the phase term of the inverse Fourier
      transform of the Fourier spectrum that corresponds to the harmonic signal. The
      mathematics and the corresponding simulation results are given for each procedure
      when applying the Fourier analysis method. The present work provides a detailed
      view of the WMS technique when applying the Fourier analysis method. 

PMID- 25968507
TI  - Total variation regularized deconvolution for extended depth of field microscopy.
AB  - The depth of field of an optical system can be extended through a combination of
      point spread function (PSF) engineering and image processing. A phase mask
      inserted in the back aperture of the system creates a PSF that is focus-invariant
      over an extended depth. A digital deconvolution is then used to restore
      transverse resolution. The application and analysis of this technique to
      fluorescence microscopy is limited in the literature. In this paper we formalize
      a microscopy specific imaging model, and experimentally demonstrate a total
      variation regularized deconvolution approach. Results are compared to the Wiener
      filter. 

PMID- 25968508
TI  - Directional support value of Gaussian transformation for infrared small target
      detection.
AB  - Robust small target detection is one of the key techniques in IR search and
      tracking systems for self-defense or attacks. In this paper we present a robust
      solution for small target detection in a single IR image. The key ideas of the
      proposed method are to use the directional support value of Gaussian transform
      (DSVoGT) to enhance the targets, and use the multiscale representation provided
      by DSVoGT to reduce the false alarm rate. The original image is decomposed into
      sub-bands in different orientations by convolving the image with the directional
      support value filters, which are deduced from the weighted mapped least-squares
      support vector machines (LS-SVMs). Based on the sub-band images, a support value
      of Gaussian matrix is constructed, and the trace of this matrix is then defined
      as the target measure. The corresponding multiscale correlations of the target
      measures are computed for enhancing target signal while suppressing the
      background clutter. We demonstrate the advantages of the proposed method on real
      IR images and compare the results against those obtained from standard detection
      approaches, including the top-hat filter, max-mean filter, max-median filter, min
      local-Laplacian of Gaussian (LoG) filter, as well as LS-SVM. The experimental
      results on various cluttered background images show that the proposed method
      outperforms other detectors. 

PMID- 25968509
TI  - Detection range enhancement using circularly polarized light in scattering
      environments for infrared wavelengths.
AB  - We find for infrared wavelengths that there are broad ranges of particle sizes
      and refractive indices that represent fog and rain, where circular polarization
      can persist to longer ranges than linear polarization. Using polarization
      tracking Monte Carlo simulations for varying particle size, wavelength, and
      refractive index, we show that, for specific scene parameters, circular
      polarization outperforms linear polarization in maintaining the illuminating
      polarization state for large optical depths. This enhancement with circular
      polarization can be exploited to improve range and target detection in obscurant
      environments that are important in many critical sensing applications. Initially,
      researchers employed polarization-discriminating schemes, often using linearly
      polarized active illumination, to further distinguish target signals from the
      background noise. More recently, researchers have investigated circular
      polarization as a means to separate signal from noise even more. Specifically, we
      quantify both linearly and circularly polarized active illumination and show here
      that circular polarization persists better than linear for radiation fog in the
      short-wave infrared, for advection fog in the short-wave and long-wave infrared,
      and large particle sizes of Sahara dust around the 4 MUm wavelength. Conversely,
      we quantify where linear polarization persists better than circular polarization
      for some limited particle sizes of radiation fog in the long-wave infrared, small
      particle sizes of Sahara dust for wavelengths of 9-10.5 MUm, and large particle
      sizes of Sahara dust through the 8-11 MUm wavelength range in the long-wave
      infrared. 

PMID- 25968510
TI  - Design and alignment strategies of 4f systems used in the vectorial optical field
      generator.
AB  - In this paper, the design and alignment strategies of 4f systems used in the
      vectorial optical field generator are described in detail. Reflection-type 4f
      systems were adopted due to limited spacing. Alignment patterns are designed and
      introduced as alignment tools so that the optical property (degree of freedom)
      controlled by each specific spatial light modulator section can be visualized and
      alignment of the 4f systems can be performed using the CCD image sharpness as the
      metric. In particular, blurring due to diffraction effects is minimized when the
      4f system is fully aligned. 

PMID- 25968511
TI  - Tunable plasmon-induced transparency in hybrid waveguide-magnetic resonance
      system.
AB  - We present a hybrid waveguide-magnetic resonance system with split ring
      resonators (SRRs) periodically arranged on top of a waveguide layer. Due to the
      destructive interference between the electric coupling to the magnetic resonance
      mode generated in the SRRs and the TE/TM waveguide modes supported by the
      waveguide layer, double plasmon-induced transparency is obtained at the infrared
      wavelength. Furthermore, the PIT resonance can be dynamically tuned by the
      incident angle. An ultranarrow PIT window with an FWHM of 7 nm is observed at the
      wavelength of 1.448 MUm. The group index at the narrow PIT window can reach up to
      100. We also demonstrate that the refractive index sensitivity and the figure of
      merit value can reach up to 640  nm/RIU and 64 in the sensing range,
      respectively. The proposed hybrid waveguide-magnetic resonance system with a high
      quality factor PIT window is promising for efficient optical sensing, optical
      switching, and slow-light device design. 

PMID- 25968512
TI  - Digital holography with multidirectional illumination by LCoS SLM for topography
      measurement of high gradient reflective microstructures.
AB  - In this paper we present a method for topography measurement of high gradient
      reflective microstructures that overcomes the limited numerical aperture (NA) of
      a digital holographic (DH) system working in reflection. We consider a case when
      a DH system is unable to register the light reflected from the full sample area
      due to insufficient NA. To overcome this problem, we propose digital holography
      in a microscope configuration with an afocal imaging system and a modified object
      arm in the measurement setup. The proposed modification includes application of a
      spatial light modulator (SLM) based on liquid crystal on silicon (LCoS)
      technology for multidirectional plane wave illumination. The variable off-axis
      illumination enables characterization of the sample regions that cannot be imaged
      by the limited NA of a classical DH system utilizing on-axis illumination. In the
      proposed method, the final object topography is merged from a set of captured
      object waves corresponding to various illumination directions using a novel
      automatic algorithm. The proposed technique is experimentally validated by full
      field measurement of a silicon mold with a high gradient of shape. 

PMID- 25968513
TI  - Technology for radiation efficiency measurement of high-power halogen tungsten
      lamp used in calibration of high-energy laser energy meter.
AB  - The calibration method using a high-power halogen tungsten lamp as a calibration
      source has many advantages such as strong equivalence and high power, so it is
      very fit for the calibration of high-energy laser energy meters. However, high
      power halogen tungsten lamps after power-off still reserve much residual energy
      and continually radiate energy, which is difficult to be measured. Two measuring
      systems were found to solve the problems. One system is composed of an
      integrating sphere and two optical spectrometers, which can accurately
      characterize the radiative spectra and power-time variation of the halogen
      tungsten lamp. This measuring system was then calibrated using a normal halogen
      tungsten lamp made of the same material as the high-power halogen tungsten lamp.
      In this way, the radiation efficiency of the halogen tungsten lamp after power
      off can be quantitatively measured. In the other measuring system, a wide
      spectrum power meter was installed far away from the halogen tungsten lamp; thus,
      the lamp can be regarded as a point light source. The radiation efficiency of
      residual energy from the halogen tungsten lamp was computed on the basis of
      geometrical relations. The results show that the halogen tungsten lamp's
      radiation efficiency was improved with power-on time but did not change under
      constant power-on time/energy. All the tested halogen tungsten lamps reached
      89.3% of radiation efficiency at 50 s after power-on. After power-off, the
      residual energy in the halogen tungsten lamp gradually dropped to less than 10%
      of the initial radiation power, and the radiation efficiency changed with time.
      The final total radiation energy was decided by the halogen tungsten lamp's
      radiation efficiency, the radiation efficiency of residual energy, and the total
      power consumption. The measuring uncertainty of total radiation energy was 2.4%
      (here, the confidence factor is two). 

PMID- 25968514
TI  - What is a Hartmann test?
AB  - In this paper we will review some of the many different practical arrangements
      that have been obtained to measure the transversal aberrations of optical systems
      based on the odd and vulnerable Hartmann test. There are many optical testing
      configurations that apparently are not related to the original Hartmann test.
      However, they are really the same thing and can be considered just a variation of
      the same basic arrangement, as will be described here. 

PMID- 25968515
TI  - Region specific enhancement of quantum dot emission using interleaved two
      dimensional photonic crystals.
AB  - The power efficiency, spectral characteristics, and output directionality of
      light emitting diodes (LEDs) used for lighting and video display may be tailored
      by integrating nanostructures that interact with photon emitters. In this work,
      we demonstrate an approach in which visible-wavelength-emitting quantum dots
      (QDs) are integrated within a polymer-based photonic crystal (PC) and excited by
      an ultraviolet-emitting LED. The PC design incorporates two interleaved regions,
      each with distinct periods in orthogonal directions. The structure enables
      simultaneous resonant coupling of ultraviolet excitation photons to the QDs and
      visible QD emission at two different wavelengths to efficiently extract photons
      normal to the PC surface. The combined excitation and extraction enhancements
      result in a 5.8X increase in the QD output intensity. Further, we demonstrate
      multiple QD-doped PCs combined on a single surface to optimally couple with
      distinct populations of QDs, offering a means for blending color output and
      directionality of multiple wavelengths. Devices are fabricated upon flexible
      plastic surfaces by a manufacturable replica molding approach. 

PMID- 25968516
TI  - Resolution enhancement of two-photon microscopy via intensity-modulated laser
      scanning structured illumination.
AB  - Conventional structured illumination microscopy (SIM) with wide-field
      illumination is an applicable tool to provide resolution enhancement. And yet its
      applications in thick specimens are still full of challenges. By combing the
      structured illumination concept with two-photon excitation, a laser scanning two
      photon structured illumination microscope (LSTP-SIM) was constructed to gain
      ~1.42-fold lateral resolution enhancement in contrast to two-photon fluorescence
      microscopy. With a point-scanning geometry, an acoustic-optical modulator was
      used to modulate temporally the excitation intensity in order to produce the
      structured illumination pattern. The theoretical models of image formation and
      image reconstruction were clearly established. Simulation and experiments were
      both performed to show the capability of this system to enhance the lateral
      resolution. Combined with the inherent optical sectioning power of the two-photon
      excitation, LSTP-SIM would have the potential for applications in optically-thick
      specimens. 

PMID- 25968517
TI  - Fiber-coupling efficiency of Gaussian Schell model for optical communication
      through atmospheric turbulence.
AB  - In practice, due to the laser device and the inevitable error of the processing
      technique, the laser source emitted from the communication terminal is partially
      coherent, and is represented as a Gaussian Schell model (GSM). The cross-spectral
      density function based on the Gaussian model in previous research is replaced by
      the GSM. Thus the fiber-coupling efficiency equation of the GSM laser source
      through atmospheric turbulence is deduced. The GSM equation presents the effect
      of the source coherent parameter zeta on the fiber-coupling efficiency, which was
      not included previously. The effects of the source coherent parameter zeta on the
      spatial coherent radius and the fiber-coupling efficiency through atmospheric
      turbulence are numerically simulated and analyzed. The result manifests that the
      fiber-coupling efficiency invariably degrades with increasing zeta. The work in
      this paper is aimed to improve the redundancy design of fiber-coupling receiver
      systems by analyzing the fiber-coupling efficiency with the source coherent
      parameters. 

PMID- 25968518
TI  - Birefringent phase demodulator: application to wave plate characterization.
AB  - The scope of this work is to present a phase demodulator that enables the
      recovery of temporal phase information contained in the phase difference between
      two signals with different polarizations. This demodulator is a polarization
      interferometer that may consist only of a uniaxial crystal slab and a polarizer
      sheet. The phase shift between two orthogonal components of the electric field is
      translated into space by means of birefringent crystals, which act as
      demodulators or phase analyzers with great robustness. The experimental scheme
      utilized is based on a simple conoscopic interference setup. Each portion of the
      space in which the interference pattern is projected contains not only the
      unknown temporal phase we want to recover, but also a phase shift due to the
      uniaxial crystal itself. The underlying idea is developing simultaneous phase
      shifting with uniaxial crystals. Thus, different phase recovery techniques can be
      applied in order to maximize their ability to track high-speed signals. Depending
      on the characteristics of the fringe pattern, it will permit phase recovery via
      different classical procedures. In order to prove the demodulator under different
      experimental and signal processing schemes, we employed it for wave plate
      characterization. The results obtained not only allow some wave plate features
      such as axes determination and retardance to be characterized, but also prove the
      working principle and capabilities of the demodulator. 

PMID- 25968519
TI  - Simultaneous physical retrieval of Martian geophysical parameters using Thermal
      Emission Spectrometer spectra: the phi-MARS algorithm.
AB  - In this paper, we present a new methodology for the simultaneous retrieval of
      surface and atmospheric parameters of Mars. The methodology is essentially based
      on similar codes implemented for high-resolution instruments looking at Earth,
      supported by a statistical retrieval procedure used to initialize the physical
      retrieval algorithm with a reliable first guess of the atmospheric parameters.
      The methodology has been customized for the Thermal Emission Spectrometer (TES),
      which is a low-resolution interferometer. However, with minor changes to the
      forward and inverse modules, it is applicable to any instrument looking at Mars,
      and with particular effectiveness to high-resolution instruments. The forward
      module is a monochromatic radiative transfer model with the capability to
      calculate analytical Jacobians of any desired geophysical parameter. In the
      present work, we describe the general methodology and its application to a large
      sample of TES spectra. Results are drawn for the case of surface temperature and
      emissivity, atmospheric temperature profile, water vapor, and dust and ice mixing
      ratios. Comparison with climate models and other TES data analyses show very good
      agreement and consistency. 

PMID- 25968520
TI  - Elasto-optic effect anisotropy in calcium tungstate crystals.
AB  - The anisotropy of piezo- and elasto-optic effects in calcium tungstate
      CaWO<sub>4</sub> crystals was studied by the indicatory surfaces method. On the
      basis of the maximum surfaces of the elasto-optic effect, the geometry of acousto
      optic interaction with maximum efficiency was found. 

PMID- 25968521
TI  - Torsion-induced optical rotation in isotropic glass media.
AB  - We have revealed that torsion stresses produce an optical activity effect in
      initially isotropic glass media. The optical activity caused by spatially
      inhomogeneous mechanical stresses has been experimentally studied for a standard
      glass BK7 subjected to torques, using a single-beam polarimetry and a polarizer
      sample-analyzer scheme. The torsion-gyration coefficient for the BK7 glass has
      been determined as (3.96+/-0.82)*10<sup>-17</sup>  m<sup>3</sup>/N. 

PMID- 25968522
TI  - Estimation of the composition of coelectron-beam-evaporated thin-mixture films by
      making use of the Wiener bounds.
AB  - Material mixtures offer prospective possibilities for synthesizing coating
      materials with tailored optical constants. We present experimental results for
      mixture coatings of alumina/aluminum fluoride and alumina/hafnia deposited by
      electron beam evaporation. Thereby, the volume filling factors of the components
      are commonly estimated on the basis of deposition rates measured by quartz
      crystal microbalance. The interplay between the vapor fluxes from the two
      evaporation sources, the crosstalk between quartz crystal microbalances, and the
      influence of the plasma source on the tooling factors limit the accuracy of this
      estimation, and this has motivated us to develop an alternative approach. The
      general idea of our approach is based on the commonly high accuracy in thin-film
      optical constant determination using spectrophotometry. Therefore, these optical
      constants serve as a reliable input for a rather simple but robust evaluation
      procedure based on the concept of Wiener bounds. The consistency of the obtained
      results is illustrated by opposing the data to the elementary film composition
      estimated from energy-dispersive x-ray spectroscopy. 

PMID- 25968523
TI  - All-glass extrinsic Fabry-Perot interferometer thermo-optic coefficient sensor
      based on a capillary bridged two fiber ends.
AB  - An all-glass extrinsic Fabry-Perot interferometer (EFPI) is demonstrated for
      thermal-optic coefficient (TOC) of water, glycerol, and their mixture (volume
      ratio of 1:1). The compensation for the thermal expansion of Fabry-Perot (FP)
      cavity is realized by assembling a glass capillary and optical fibers through a
      CO<sub>2</sub> laser welding. The thermal responses of EFPIs are tested in air at
      different cavity lengths of 578.6 MUm, 911.7 MUm, and 1520.3 MUm, respectively.
      The corresponding refractive index errors induced by thermal expansion of FP
      cavity are negligible, which are demonstrated to be 4.33*10<sup>-6</sup>  RIU/
      degrees C, 4.13*10<sup>-6</sup>  RIU/ degrees C, and 3.45*10<sup>-6</sup>  RIU/
      degrees C when temperature increases from 20.03 degrees C to 60.78 degrees C. The
      thermal-optic coefficients of water, glycerol, and their mixture are measured to
      be -1.5*10<sup>-4</sup>  RIU/ degrees C, -2.3*10<sup>-4</sup>  RIU/ degrees C,
      and -2.0*10<sup>-4</sup>  RIU/ degrees C, respectively. Our study suggests a
      potential use of this sensor for TOC measurements of liquids with the advantages
      of low costs and robustness. 

PMID- 25968524
TI  - Ultra-flexible polarization-insensitive multiband terahertz metamaterial
      absorber.
AB  - A thin-flexible and polarization-insensitive multiband terahertz metamaterial
      absorber (MMA) has been investigated. Each unit cell of the MMA consists of two
      metallic structures, which include the top metal resonator ring and the bottom
      metal ground plane, separated by a thin-flexible dielectric spacer. Finite
      element simulation indicates that this MMA has three high absorption peaks in the
      terahertz region, with absorptivities of 89% at 0.72 THz, 98% at 1.4 THz, and 85%
      at 2.3 THz. However, because of its rotationally symmetric structure, this MMA is
      polarization-insensitive and can perform very well at a wide range of incident
      angles, namely, 30 degrees  for transverse electric waves and 40 degrees  for
      transverse magnetic waves. The thin-flexible device structure and good
      performance shows that this MMA is very promising to disguise objects and make
      them less detectable to radar in the terahertz region. 

PMID- 25968525
TI  - Study of the effect introduced by an integrating sphere on the temporal profile
      characterization of short laser pulses propagating through a turbid medium.
AB  - When a nanosecond laser pulse is transmitted through a highly scattering
      material, its irradiance decreases as it propagates; this is because of the
      spatial and temporal pulse profile stretching owing to multiple scattering
      events. Although the effect of temporal distortion is much less significant than
      that of the spatial distortion for applications where the laser beam is focused
      on a subsurface target (writing of waveguides, for example), it becomes
      significant for applications where the laser pulse must attain certain temporal
      width after the beam propagated is collimated through a turbid medium
      (photoacoustic tomography, for example). The objective of this work is to
      determine the transfer function associated to an integrating sphere measurement
      of the temporal intensity profile involving turbid media samples. The transfer
      function is found to be related to the geometrical characteristics of the
      integrating sphere and the optical properties of the turbid media. This procedure
      opens a new possibility for optical property characterization and enables the use
      of an integrating sphere for time-dependent intensity measurements. 

PMID- 25968526
TI  - Absolute calibration of a spectrometer using terrestrial solar radiation.
AB  - We present a method to provide absolute intensity calibration of a common low
      resolution, wideband optical spectrometer. Terrestrial solar radiation is
      employed as the source of illumination, and the spectrometer output is compared
      to a solar spectral standard to determine its calibration. Over 3  days of
      observation, the procedure is demonstrated to yield reproducible results. Other
      evidence of calibration accuracy is presented. 

PMID- 25968527
TI  - Tailoring freeform illumination optics in a double-pole coordinate system.
AB  - We have developed a new method to design freeform illumination optics by
      introducing a double-pole coordinate system in ray mapping. This method
      establishes a much more accurate ray mapping by moving the two poles of the
      spherical coordinate system to the southernmost point of the sphere and
      overlapping them together. It can reduce surface error and improve illumination
      uniformity significantly. The residual surface error (RSE) of the freeform lens
      designed in the double-pole coordinate system is one magnitude smaller than that
      of the lens designed in the (theta,phi) coordinate system and is only 1/3 of that
      of the freeform surface designed in the (u,v) coordinate system. 

PMID- 25968528
TI  - Random numbers free analytical implementation of Monte Carlo for laser-Doppler
      flowmetry at large interoptode spacing: application to human bone tissue.
AB  - Classical Monte Carlo (MC) simulations for laser-Doppler flowmetry (LDF) often
      necessitate too long computation times and specialized hardware. This is
      particularly true for LDF at large interoptode spacing with low absorption
      coefficients and large anisotropic factors representing real biological tissues.
      For this reason, a random numbers free "analytical" implementation of the
      classical MC (MC<sub>an</sub>) is proposed. The MC<sub>an</sub> approach allows
      to obtain noise exempt LDF spectra in a short time and with a simple personal
      laptop. The proposed MC<sub>an</sub> holds for a diffusive regime of light
      propagation and it is practically implemented for a semi-infinite geometry. Its
      validity is demonstrated by comparisons with the classical MC. 

PMID- 25968529
TI  - Spectro-temporal dynamics of Kerr combs with parametric seeding.
AB  - We report a joint theoretical and experimental investigation of the parametric
      seeding of a primary Kerr optical frequency comb. Electro-optic modulation
      sidebands matching multiple free-spectral ranges of an ultrahigh-Q millimeter
      size magnesium fluoride disk resonator are used as seed signals. These seed
      signals interact through four-wave mixing with the spectral components of a
      stable primary comb and give rise to complex spectro-temporal patterns. We show
      that the new frequency combs feature multiscale frequency spacing, with major
      frequency gaps in the order of a few hundred gigahertz, and minor frequency
      spacing in the order of a few tens of gigahertz. The experimental results are in
      agreement with numerical simulations using the Lugiato-Lefever equation. We
      expect such versatile and coherent optical frequency combs to have potential
      applications in optical communications systems where frequency management assigns
      predefined spectral windows at the emitter stage. 

PMID- 25968530
TI  - Optical design considerations for efficient light collection from liquid
      scintillation counters.
AB  - Liquid scintillation counters measure charged particle-emitting radioactive
      isotopes and are used for environmental studies, nuclear chemistry, and life
      science. Alpha and beta emissions arising from the material under study interact
      with the scintillation cocktail to produce light. The prototypical liquid
      scintillation counter employs low-level photon-counting detectors to measure the
      arrival of the scintillation. For reliable operation, the counting instrument
      must convey the scintillation light to the detectors efficiently and predictably.
      Current best practices employ the use of two or more detectors for coincidence
      processing to discriminate true scintillation events from background events due
      to instrumental effects such as photomultiplier tube dark rates, tube flashing,
      or other light emission not generated in the scintillation cocktail vial. In low
      background liquid scintillation counters, additional attention is paid to
      shielding the scintillation cocktail from naturally occurring radioactive
      material present in the laboratory and within the instrument's construction
      materials. Low-background design is generally at odds with optimal light
      collection. This study presents the evolution of a light collection design for
      liquid scintillation counting (LSC) in a low-background shield. The basic
      approach to achieve both good light collection and a low-background measurement
      is described. The baseline signals arising from the scintillation vial are
      modeled and methods to efficiently collect scintillation light are presented as
      part of the development of a customized low-background, high-sensitivity LSC
      system. 

PMID- 25968531
TI  - Practical algorithms for simulation and reconstruction of digital in-line
      holograms.
AB  - Here we present practical methods for simulation and reconstruction of in-line
      digital holograms recorded with plane and spherical waves. The algorithms
      described here are applicable to holographic imaging of an object exhibiting
      absorption as well as phase-shifting properties. Optimal parameters, related to
      distances, sampling rate, and other factors for successful simulation and
      reconstruction of holograms are evaluated and criteria for the achievable
      resolution are worked out. Moreover, we show that the numerical procedures for
      the reconstruction of holograms recorded with plane and spherical waves are
      identical under certain conditions. Experimental examples of holograms and their
      reconstructions are also discussed. 

PMID- 25968532
TI  - Nano-indentation of single-layer optical oxide thin films grown by electron-beam
      deposition.
AB  - Mechanical characterization of optical oxide thin films is performed using nano
      indentation, and the results are explained based on the deposition conditions
      used. These oxide films are generally deposited to have a porous microstructure
      that optimizes laser induced damage thresholds, but changes in deposition
      conditions lead to varying degrees of porosity, density, and possibly the
      microstructure of the thin film. This can directly explain the differences in the
      mechanical properties of the film studied here and those reported in literature.
      Of the four single-layer thin films tested, alumina was observed to demonstrate
      the highest values of nano-indentation hardness and elastic modulus. This is
      likely a result of the dense microstructure of the thin film arising from the
      particular deposition conditions used. 

PMID- 25968533
TI  - Computational method for correcting complex optical distortion based on FOV
      division.
AB  - We propose a computational method for correcting complex optical distortion in
      off-axis optical systems, such as the optical systems found in head-mounted and
      head-up displays. The proposed method divides the wide field of view (FOV) into
      subsections, thereby allowing the distortion to be calculated for each small FOV.
      Instead of applying the conventional distortion model, the distortion
      coefficients for each small FOV can be calculated using a simple linear
      polynomial. In addition, in contrast to the conventional distortion coefficients
      that refer to the deviation between the real and paraxial image, the distortion
      coefficients employed by this method directly characterize the relationship
      between the object and its image. Thus, using the polynomial in the reverse
      manner repeatedly for each small FOV with the corresponding distortion
      coefficients, a pixel lookup table is obtained, which can be used to accurately
      compensate for the distortion in the optical system. This method avoids
      complicated computations, and there are no requirements for intrinsic or
      extrinsic parameters. Our experiments verified the effectiveness of the method
      where the root-mean-square deviation of the projected distorted straight lines
      was corrected from 23 to 65 pixels to approximately 1 pixel. 

PMID- 25968534
TI  - Experimental investigation on butane diffusion flames under the influence of
      magnetic field by using digital speckle pattern interferometry.
AB  - In this paper, the effect of magnetic fields on the temperature and temperature
      profile of a diffusion flame obtained from a butane torch burner are investigated
      experimentally by using digital speckle pattern interferometry (DSPI).
      Experiments were conducted on a diffusion flame generated by a butane torch
      burner in the absence of a magnetic field and in the presence of uniform and
      nonuniform magnetic fields. A single DSPI fringe pattern was used to extract
      phase by using a Riesz transform and monogenic signal. Temperature inside the
      flame was determined experimentally both in the absence and in the presence of
      magnetic fields. Experimental results reveal that the maximum temperature of the
      flame is increased under the influence of an upward-decreasing magnetic gradient
      and decreased under an upward-increasing magnetic gradient while a negligible
      effect on temperature in a uniform magnetic field was observed. 

PMID- 25968535
TI  - Compact triple coupled quantum well system for electrical/optical control of
      optical bi/multistability.
AB  - Optical bistability (OB) and optical multistability (OM) are investigated in a
      triple coupled quantum wells system inside a semiconductor cavity sandwiched by
      distributed Bragg reflector mirrors. By proper manipulation of the optical and
      electrical parameters, the behaviors of OB and OM can be efficiently controlled.
      We show that, by tuning the tunneling rates between the quantum wells, the
      threshold and hysteresis cycle of OB and OM can be engineered. The effect of the
      incoherent pump field as well as the cooperation parameter on creation of OB is
      also discussed. 

PMID- 25968536
TI  - Fiber laser-based scanning lidar for space rendezvous and docking.
AB  - Lidar systems have played an important role in space rendezvous and docking
      (RVD). A new type of scanning lidar is developed using a high-repetition-rate
      pulsed fiber laser and a position detector. It will be a candidate for autonomous
      space RVD between two spacecrafts. The lidar can search and track cooperative
      targets in a large region without artificial guidance. The lidar's operational
      range spans from 18 m to 20 km, and the relative angle between two aircrafts can
      be measured with high accuracy. A novel fiber laser with tunable pulse energy and
      repetition rate is developed to meet the wide dynamic detection range of the
      lidar. This paper presents the lidar system's composition, performance, and
      experimental results in detail. 

PMID- 25968537
TI  - Calculation of laser absorption by metal powders in additive manufacturing.
AB  - We have calculated the absorption of laser light by a powder of metal spheres,
      typical of the powder employed in laser powder-bed fusion additive manufacturing.
      Using ray-trace simulations, we show that the absorption is significantly larger
      than its value for normal incidence on a flat surface, due to multiple
      scattering. We investigate the dependence of absorption on powder content
      (material, size distribution, and geometry) and on beam size. 

PMID- 25968538
TI  - Innovative measurement of parallelism for parallel transparent plate based on
      optical scanning holography by using a random-phase pupil.
AB  - A potential method is proposed to measure the parallelism of parallel transparent
      plate with an advanced lower limit and a convenient process by optical scanning
      holography (OSH) using a random-phase pupil, which is largely distinct from
      traditional methods. As a new possible application of OSH, this promising method
      is demonstrated theoretically and numerical simulations are carried out on a 2 
      cm*2  cm parallel plate. Discussions are also made on the quality of
      reconstructed image as well as local mean square error (MSE), which are closely
      related with the parallelism of sample. These amounts may become the judgments of
      parallelism, while in most interference methods judgments are paces between two
      interference fringes. In addition, randomness of random-phase pupil also affects
      the quality of reconstructed image and local MSE. According to the simulation
      results, high parallelism usually brings about distinguishable reconstructed
      information and suppressed local MSE. 

PMID- 25968539
TI  - Millijoule-level picosecond mid-infrared optical parametric amplifier based on
      MgO-doped periodically poled lithium niobate.
AB  - A millijoule-level high pulse energy picosecond (ps) mid-infrared (MIR) optical
      parametric amplifier (OPA) at 3.9 MUm based on large-aperture MgO-doped
      periodically poled lithium niobate (MgO:PPLN) crystal was demonstrated for the
      first time, to the best of our knowledge. The MIR OPA was pumped by a 30 ps 1064
      nm Nd:YAG laser at 10 Hz and injected by an energy-adjustable near-infrared seed
      based on a barium boron oxide (BBO) optical parametric generator/optical
      parametric amplifier (OPG/OPA) with double-pass geometry. Output energy of 1.14
      mJ at 3.9 MUm has been obtained at pump energy of 15.2 mJ. Furthermore, the
      performance of MIR OPG in MgO:PPLN was also investigated for comparing with the
      seeded OPA. 

PMID- 25968540
TI  - Laser beam splitting by polarization encoding.
AB  - A scheme is proposed to design a polarization grating that splits an incident
      linearly polarized beam to an array of linearly polarized beams of identical
      intensity distribution and various azimuth angles of linear polarization. The
      grating is equivalent to a wave plate with space-variant azimuth angle and space
      variant phase retardation. The linear polarization states of all split beams make
      the grating suitable for coherent beam combining architectures based on Dammann
      gratings. 

PMID- 25968541
TI  - Low threshold Er(x)Yb(Y)(2-x)SiO(5) nanowire waveguide amplifier.
AB  - The 1.53 MUm gain characteristics of Er<sub>x</sub>Yb(Y)<sub>2
      x</sub>SiO<sub>5</sub> nanowire and film material waveguide amplifiers have been
      investigated considering the upconversion effect by solving rate equations and
      propagation equations. The gains of Er<sub>x</sub>Yb(Y)<sub>2
      x</sub>SiO<sub>5</sub> nanowire waveguides have a significant enhancement
      compared with those of film material waveguides due to low propagation loss and
      long photoluminescence lifetime. The cooperative upconversion (CUC) effect plays
      a significant role in the simulation. The maximum 27 dB/mm gain for a 1 mm length
      Er<sub>x</sub>Yb(Y)<sub>2-x</sub>SiO<sub>5</sub> nanowire waveguide was obtained
      without CUC, and only about 2 dB/mm gain was obtained with CUC. However, the low
      thresholds of 10.7 and 0.7 mW, respectively, for the Er<sub>x</sub>Y<sub>2
      x</sub>SiO<sub>5</sub> and Er<sub>x</sub>Yb<sub>2-x</sub>SiO<sub>5</sub> nanowire
      waveguides amplifiers were observed with CUC by analyzing the relation between
      optical gain and the Er/Yb/Y concentration, waveguide length, waveguide cross
      section area, energy-level lifetime, and pumping power coefficients. The low
      threshold is two to three orders of magnitude lower than the threshold used in
      thin film experiments. 

PMID- 25968542
TI  - Theoretical and experimental study on anamorphosis correction of Czerny-Turner
      imaging spectrometers.
AB  - The structure of an astigmatism-corrected Czerny-Turner imaging spectrometer will
      produce the focal length difference between sagittal rays and tangential rays,
      which contributes to the magnification difference in the spectral and spatial
      dimensions of the images. In this paper, the common characteristics of two
      optical path structures based on the Czerny-Turner imaging spectrometer to
      correct astigmatism (using a cylindrical and a toroidal mirror) are discussed.
      The magnification differences in the spectral and spatial dimensions of the image
      when the gratings are at zero-order and first-order diffraction and the influence
      of image magnification of different wavelengths are analyzed. The correction
      formula, methods of anamorphosis, and their common characteristics are given as
      well. The validity of the correction formula of anamorphosis is verified with
      theoretical calculation, ray tracing simulation, and experimental measurements
      with the imaging spectrometers. Meanwhile, this method is useful for the
      anamorphosis correction of an off-axis dispersion imaging spectrometer in other
      operating conditions of collimated light. 

PMID- 25968543
TI  - Direct measurement of particle size and 3D velocity of a gas-solid pipe flow with
      digital holographic particle tracking velocimetry.
AB  - The 3D measurement of the particles in a gas-solid pipe flow is of great
      interest, but remains challenging due to curved pipe walls in various engineering
      applications. Because of the astigmatism induced by the pipe, concentric ellipse
      fringes in the hologram of spherical particles are observed in the experiments.
      With a theoretical analysis of the particle holography by an ABCD matrix, the in
      focus particle image can be reconstructed by the modified convolution method and
      fractional Fourier transform. Thereafter, the particle size, 3D position, and
      velocity are simultaneously measured by digital holographic particle tracking
      velocimetry (DHPTV). The successful application of DHPTV to the particle size and
      3D velocity measurement in a glass pipe's flow can facilitate its 3D diagnostics.

PMID- 25968544
TI  - Assembly of silver nanoparticles on nanowires into ordered nanostructures with
      femtosecond laser radiation.
AB  - In this work, we show that well-ordered structures of silver nanoparticles on
      nanowire substrates can be produced by irradiation with femtosecond (fs) laser
      pulses at fluences ranging from 10.3 to 15.9  mJ/cm<sup>2</sup> if the direction
      of polarization is parallel to the long axis of the nanowire. Experimental
      results show that a uniformly spaced distribution of nanoparticles is more
      readily produced on nanowires with lengths L<=2lambda, where lambda=800  nm is
      the laser wavelength. The distribution of nanoparticles is found to become less
      well organized as L>=2lambda. Finite element method simulations, combined with
      experimental observations, indicate that nanoparticles are initially distributed
      in response to the electric field along the clean Ag nanowire arising from
      optical excitation. This electric field is responsible for the attraction of
      nanoparticles to certain locations on the nanowire. We show how a fs-laser-driven
      assembly of nanoparticles on nanowires can be used in the development of a
      nanoscale optical logic processor. This method of creating periodic arrays of
      metallic nanoparticles on nanowire substrates then has many possible applications
      in electro-optics. 

PMID- 25968545
TI  - Nonunified integral imaging elemental image array generation method based on
      selective pixel sampling algorithm.
AB  - We propose a method based on the selective pixel sampling algorithm to generate a
      nonunified integral imaging (II) elemental image array (EIA) with reduced moire
      patterns at a low rendering cost and high three-dimensional (3D) resolution. In
      the proposed method, the redundant 3D information is captured for the nonunified
      pixel arrangement of elemental images, and the moire patterns are constrained by
      the constraint equations. The nonunified EIA's corresponding information is
      mapped from the obtained 3D information based on the selective pixel sampling
      algorithm. Appropriate experiments are carried out, and the experimental results
      show that the proposed method can increase the 3D display quality of the
      reconstructed 3D images in the II display and reduce rendering costs markedly in
      the generation of ultra-high-definition EIA. 

PMID- 25968546
TI  - Gold nanopillar arrays as biosensors fabricated by electron beam lithography
      combined with electroplating.
AB  - We report our work on the development of subwavelength gold pillar arrays as
      local surface plasmonic (LSP) resonators for sensor applications. These arrays
      are fabricated by electron beam lithography combined with electroplating. The
      conical shape, instead of flat one, on the top of Au pillars, induced by uneven
      current density in the plating, may affect the LSP resonance (LSPR). This paper
      aims to carry out a systematic study of LSPR behavior in nanopillar arrays with
      both flat and conical shapes on the top, trying to prove the feasibility of the
      developed nanoprocess. Both numerical simulations by the finite-difference time
      domain (FDTD) method and experimental characterization on fabricated LSP
      resonators for reflectance spectra were carried out. Our experiments indicate
      that the fabricated nanopillar arrays in Au demonstrate the promising capability
      of refractive index sensing with sensitivity of 270 nm/refractive index unit.
      FDTD simulation of electric field density in the gap between pillars reveals the
      correlation between the resonant absorption of the incident light and the
      standing waves of localized surface plasmon polaritons in the gaps of the pillar
      array, despite the conical shape of the pillars. Moreover, it was discovered that
      the resonant absorption becomes stronger when the light incident angle is
      increased. The proposed nanoprocess for pillar arrays should possess great
      prospects for manufacturing Au pillars with high aspect ratio for achieving
      higher sensitivity at an economical cost. 

PMID- 25968547
TI  - Polarizer based upon a plasmonic resonant thin layer on a squeezed photonic
      crystal fiber.
AB  - In this article, a polarizer based on surface plasmon resonance in a squeezed
      rectangular lattice is analyzed through a full-vector finite-element method
      solver. The device allows one state of polarization (e.g., y-polarized mode) to
      propagate through the fiber while the other state (x-polarized mode) is heavily
      attenuated: the modal losses for the x- and y-polarized modes are 1221 dB/cm and
      1.6 dB/cm, respectively, at the wavelength of 1310 nm. Given the high
      differential attenuation between the two orthogonal polarization modes, the
      device could be used as a compact polarizer with potential applications in
      sensing, communications, and other areas. 

PMID- 25968548
TI  - Rigorous analysis of acoustic modes in low and high index contrast silica fibers.
AB  - The vector acoustic modes in both well-established and emerging designs of
      optical waveguides have been studied through use of a computer code which has
      been developed based on the finite element method (FEM). Dispersion curves and
      the displacement vectors for the transverse and longitudinal acoustic modes and
      the modal hybridness have been determined and these are shown for both low and
      high index contrast silica (SiO<sub>2</sub>) acoustic waveguides. Stimulated
      Brillouin scattering (SBS) frequencies are also reported for the subwavelength
      size SiO<sub>2</sub> optical waveguides. 

PMID- 25968550
TI  - History as an educational tool in Physical and Rehabilitation Medicine. A call
      for historical papers to be published in the European Journal of Physical and
      Rehabilitation Medicine.

PMID- 25968549
TI  - Brain structural changes in schizoaffective disorder compared to schizophrenia
      and bipolar disorder.
AB  - OBJECTIVE: Brain structural changes in schizoaffective disorder, and how far they
      resemble those seen in schizophrenia and bipolar disorder, have only been studied
      to a limited extent. METHOD: Forty-five patients meeting DSM-IV and RDC criteria
      for schizoaffective disorder, groups of patients with 45 matched schizophrenia
      and bipolar disorder, and 45 matched healthy controls were examined using voxel
      based morphometry (VBM). RESULTS: Analyses comparing each patient group with the
      healthy control subjects found that the patients with schizoaffective disorder
      and the patients with schizophrenia showed widespread and overlapping areas of
      significant volume reduction, but the patients with bipolar disorder did not. A
      subsequent analysis compared the combined group of patients with the controls
      followed by extraction of clusters. In regions where the patients differed
      significantly from the controls, no significant differences in mean volume
      between patients with schizoaffective disorder and patients with schizophrenia in
      any of five regions of volume reduction were found, but mean volumes in the
      patients with bipolar disorder were significantly smaller in three of five.
      CONCLUSION: The findings provide evidence that, in terms of structural gray
      matter brain abnormality, schizoaffective disorder resembles schizophrenia more
      than bipolar disorder.

PMID- 25968551
TI  - Estimation of calcium, magnesium, cadmium, and lead in biological samples from
      paralyzed quality control and production steel mill workers.
AB  - The determination of trace and toxic metals in the biological samples of human
      beings is an important clinical screening procedure. The aim of the present study
      was to compare the level of essential trace and toxic elements cadmium (Cd),
      calcium (Ca), lead (Pb), and magnesium (Mg) in biological samples (whole blood,
      urine, and scalp hair) of male paralyzed production (PPW) and quality control
      workers (PQW) of a steel mill, age ranged (35-55 years). For comparison purposes,
      healthy age-matched exposed referent subjects (EC), working in steel mill and
      control subjects (NEC), who were not working in industries and lived far away
      from the industrial areas, were selected as control subjects. The concentrations
      of electrolytes and toxic elements in biological samples were measured by atomic
      absorption spectrometry after microwave-assisted acid digestion. The validity and
      accuracy of the methodology were checked using certified reference materials. The
      results of this study showed that the mean values of Cd and Pb were significantly
      higher in scalp hair, blood, and urine samples of PPW and PQW as compared to NEC
      and EC (p < 0.001), whereas the concentrations of Ca and Mg were found to be
      lower in the scalp hair and blood but higher in the urine samples of PPW and PQW.
      The results show the need for immediate improvements in workplace, ventilation,
      and industrial hygiene practices.

PMID- 25968552
TI  - Proposed method for controlling turbid particles in solid-phase bioluminescent
      toxicity measurement.
AB  - In the recent half century, numerous methods have been developed to assess
      ecological toxicity. However, the presence of solid-particle turbidity sometimes
      causes such tests to end with questionable results. Many researchers focused on
      controlling this arbitrary turbidity effect when using the Microtox(r) solid
      phase toxicity system, but there is not yet a standard method. In this study, we
      examined four solid-phase sample test methods recommended in the Microtox(r)
      manual, or proposed from the literature, and compared the existing methods with
      our proposed method (centrifuged basic solid-phase test, c-BSPT). Four existing
      methods use the following strategies to control turbid particles: complete
      separation of liquid and solid using 0.45-MUm filtration before contacting solid
      samples and bacteria, natural settlement, moderate separation of large particles
      using coarser pore size filtration, and exclusion of light loss in the toxicity
      calculation caused by turbidity after full disturbance of samples. Our proposed
      method uses moderate centrifugation to separate out the heavier soil particles
      from the lighter bacteria after direct contact between them. Among the solid
      phase methods tested, in which the bacteria and solid particles were in direct
      contact (i.e., the three existing methods and the newly proposed one, c-BSPT), no
      single method could be recommended as optimal for samples over a range of
      turbidity. Instead, a simple screening strategy for selecting a sample-dependent
      solid-phase test method was suggested, depending on the turbidity of the solid
      suspension. The results of this study highlight the importance of considering
      solid particles, and the necessity for optimal selection of test method to reduce
      errors in the measurement of solid-phase toxicity. 

PMID- 25968553
TI  - Heavy metals fractionation and risk assessment in surface sediments of Qarun and
      Wadi El-Rayan Lakes, Egypt.
AB  - This study establishes a baseline for trace metal speciation in Qarun and Wadi El
      Rayan lakes. A five-step sequential extraction procedure was applied for the
      speciation of the Fe, Mn, Zn, and Cu in sediment samples collected at Qarun and
      Wadi El-Rayan lakes. Mn and Cu were the most mobile metals, whereas the residue
      fraction maintained the highest concentrations of Zn and Fe (~ 60 %). No
      significant differences in metal concentrations were detected in the sediments of
      each lake sites, despite of the large distance between them (P > 0.05). Hazardous
      discharge sources are responsible for the high accumulation of metals in the
      nonresidual fractions. Qarun Lake showed high mobility factor for all studied
      metals than Wadi El-Rayan lakes; as such, all the humans, plants, animals and the
      general biota within the vicinity of this aquatic system are quite vulnerable to
      the trace metal exposure. According to geoaccumulation index (I-geo), the studied
      sediments were practically uncontaminated by Fe and Mn and classified as
      uncontaminated to moderately contaminated with Cu in Qarun and Zn in Wadi El
      Rayan lakes. The low values of load pollution index (<1), confirmed the
      unpolluted condition of the lakes' superficial sediments.

PMID- 25968554
TI  - A data management and publication workflow for a large-scale, heterogeneous
      sensor network.
AB  - It is common for hydrology researchers to collect data using in situ sensors at
      high frequencies, for extended durations, and with spatial distributions that
      produce data volumes requiring infrastructure for data storage, management, and
      sharing. The availability and utility of these data in addressing scientific
      questions related to water availability, water quality, and natural disasters
      relies on effective cyberinfrastructure that facilitates transformation of raw
      sensor data into usable data products. It also depends on the ability of
      researchers to share and access the data in useable formats. In this paper, we
      describe a data management and publication workflow and software tools for
      research groups and sites conducting long-term monitoring using in situ sensors.
      Functionality includes the ability to track monitoring equipment inventory and
      events related to field maintenance. Linking this information to the
      observational data is imperative in ensuring the quality of sensor-based data
      products. We present these tools in the context of a case study for the
      innovative Urban Transitions and Aridregion Hydrosustainability (iUTAH) sensor
      network. The iUTAH monitoring network includes sensors at aquatic and terrestrial
      sites for continuous monitoring of common meteorological variables, snow
      accumulation and melt, soil moisture, surface water flow, and surface water
      quality. We present the overall workflow we have developed for effectively
      transferring data from field monitoring sites to ultimate end-users and describe
      the software tools we have deployed for storing, managing, and sharing the sensor
      data. These tools are all open source and available for others to use. 

PMID- 25968555
TI  - Tea extracts protect normal lymphocytes but not leukemia cells from UV radiation
      induced ROS production: An EPR spin trap study.
AB  - PURPOSE: An ex vivo method for detection of free radicals and their
      neutralization by aqueous tea in human normal lymphocytes and MEC-1 leukemia
      cells under ultraviolet (UV) irradiation was investigated. MATERIALS AND METHODS:
      This method is based on the electron paramagnetic resonance (EPR) spectroscopy
      spin-trapping technique. 5-tert-butoxycarbonyl 5-methyl-1-pyrroline N-oxide
      (BMPO) was used as the spin trap. Normal human lymphocytes and leukemia cells
      were exposed to UVB radiation (290-315 nm) at 47.7 and 159 mJ/cm(2) and to UVA
      radiation (315-400 nm) at 53.7 J/cm(2). RESULTS: No significant radical
      production at 47.7 mJ/cm(2) UVB dose in both cell lines was observed. In normal
      cells, free radical production was observed at 159 mJ/cm(2) UVB and 53.7 J/cm(2)
      UVA doses. However, both UV sources did not significantly produce free radicals
      in leukemia cells. A radical scavenging property of tea extracts (black, green,
      sage, rosehip) was observed in normal lymphocytes after both UVB and UVA
      exposure. In leukemia cells, the intensities of EPR signals produced in BMPO with
      tea extracts were found to be increased substantially after UVA exposure.
      CONCLUSION: These results showed that UV radiation induced free radical formation
      in normal human lymphocytes and indicated that tea extracts may be useful as
      photoprotective agents for them. On the other hand, tea extracts facilitated free
      radical production in leukemia cells.

PMID- 25968556
TI  - Cross-adaptation to cadmium stress in Plantago ovata by pre-exposure to low dose
      of gamma rays: Effects on metallothionein and metal content.
AB  - PURPOSE: To investigate the effects of gamma pre-exposure on cadmium accumulation
      in Plantago ovata seedlings. Metallothionein (MT) localization was also studied
      following Cadmium (Cd) treatment in P. ovata. MATERIALS AND METHODS: DNA damage
      was determined by alkaline comet assay. MT gene and protein expression were
      studied by real-time polymerase chain reaction and flow cytometry, respectively,
      in root and shoot tissues. Metal accumulation (Cd, zinc [Zn], iron [Fe]) was
      evaluated by Atomic Absorption Spectroscopy. RESULTS: Cd treatment decreased seed
      germination rate, biomass and free radical scavenging activity and increased DNA
      damage in a dose-dependent manner. When P. ovata seeds were pre- exposed to 5 Gy
      gamma dose (prior to Cd treatment) seed germination rate, biomass and free
      radical scavenging activity increased significantly. MT genes (PoMT1, PoMT2 and
      PoMT3) and MT protein expression enhanced when 5 Gy gamma-irradiated seeds were
      grown in Cd containing medium and Cd accumulation also increased in a dose
      dependent manner. CONCLUSIONS: Higher Cd accumulation in P. ovata seedlings may
      be attributed to the upregulation of PoMT genes in gamma pretreated seedlings.
      Localization of metallothionein in cytosol and nucleus indicated its positive
      role against Cd-mediated cytotoxic and genotoxic effects.

PMID- 25968557
TI  - Radiobiological response to ultra-short pulsed megavoltage electron beams of
      ultra-high pulse dose rate.
AB  - PURPOSE: In line with the long-term aim of establishing the laser-based particle
      acceleration for future medical application, the radiobiological consequences of
      the typical ultra-short pulses and ultra-high pulse dose rate can be investigated
      with electron delivery. MATERIALS AND METHODS: The radiation source ELBE
      (Electron Linac for beams with high Brilliance and low Emittance) was used to
      mimic the quasi-continuous electron beam of a clinical linear accelerator (LINAC)
      for comparison with electron pulses at the ultra-high pulse dose rate of 10(10)
      Gy min(-1) either at the low frequency of a laser accelerator or at 13 MHz
      avoiding effects of prolonged dose delivery. The impact of pulse structure was
      analyzed by clonogenic survival assay and by the number of residual DNA double
      strand breaks remaining 24 h after irradiation of two human squamous cell
      carcinoma lines of differing radiosensitivity. RESULTS: The radiation response of
      both cell lines was found to be independent from electron pulse structure for the
      two endpoints under investigation. CONCLUSIONS: The results reveal, that ultra
      high pulse dose rates of 10(10) Gy min(-1) and the low repetition rate of laser
      accelerated electrons have no statistically significant influence (within the 95%
      confidence intervals) on the radiobiological effectiveness of megavoltage
      electrons.

PMID- 25968558
TI  - Residential radon and lung cancer characteristics in never smokers.
AB  - PURPOSE: The aim of this study is to assess if there is a relationship between
      residential radon and lung cancer histological types and patients' age at
      diagnosis. MATERIALS AND METHODS: We conducted a multicenter hospital-based case
      control study with eight participating hospitals. We included 216 never-smoking
      cases with primary lung cancer and 329 never-smoking controls. Controls were
      frequency matched with cases on age and sex distribution. Of them, 198 cases
      (91.7%) and 275 controls (83.5%) had residential radon measurements. RESULTS:
      Lung cancer risk reached statistical significance only for adenocarcinoma (Odds
      ratio [OR] 2.19; 95% Confidence interval [CI] 1.44-3.33), for other histologies
      the results were marginally significant. Residential radon level was higher for
      patients diagnosed before 50 and 60 years old than for older lung cancer cases.
      CONCLUSIONS: Residential radon in never smokers seems to be a risk factor for all
      lung cancer histologies. Individuals diagnosed at a younger age have a higher
      residential radon concentration, suggesting an accumulative effect on lung cancer
      appearance.

PMID- 25968559
TI  - EPI-CT: in vitro assessment of the applicability of the gamma-H2AX-foci assay as
      cellular biomarker for exposure in a multicentre study of children in diagnostic
      radiology.
AB  - PURPOSE: To conduct a feasibility study on the application of the gamma-H2AX foci
      assay as an exposure biomarker in a prospective multicentre paediatric radiology
      setting. MATERIALS AND METHODS: A set of in vitro experiments was performed to
      evaluate technical hurdles related to biological sample collection in a
      paediatric radiology setting (small blood sample volume), processing and storing
      of blood samples (effect of storing blood at 4 degrees C), the reliability of
      foci scoring for low-doses (merge gamma-H2AX/53BP1 scoring), as well as the
      impact of contrast agent administration as potential confounding factor. Given
      the exploratory nature of this study and the ethical constraints related to
      paediatric blood sampling, blood samples from adult volunteers were used for
      these experiments. In order to test the feasibility of pooling the gamma-H2AX
      data when different centres are involved in an international multicentre study,
      two intercomparison studies in the low-dose range (10-500 mGy) were performed.
      RESULTS: Determination of the number of X-ray induced gamma-H2AX foci is feasible
      with one 2 ml blood sample pre- and post-computed tomography (CT) scan.
      Lymphocyte isolation and fixation on slides is necessary within 5 h of blood
      sampling to guarantee reliable results. The possible enhancement effect of
      contrast medium on the induction of DNA DSB in a patient study can be ruled out
      if radiation doses and the contrast agent concentration are within diagnostic
      ranges. The intercomparison studies using in vitro irradiated blood samples
      showed that the participating laboratories, executing successfully the gamma-H2AX
      foci assay in lymphocytes, were able to rank blind samples in order of lowest to
      highest radiation dose based on mean foci/cell counts. The dose response of all
      intercomparison data shows that a dose point of 10 mGy could be distinguished
      from the sham-irradiated control (p = 0.006). CONCLUSIONS: The results
      demonstrate that it is feasible to apply the gamma-H2AX foci assay as a cellular
      biomarker of exposure in a multicentre prospective study in paediatric CT imaging
      after validating it in an in vivo international pilot study on paediatric
      patients.

PMID- 25968560
TI  - Health, growth and reproductive success of mice exposed to environmentally
      relevant levels of Ra-226 via drinking water over multiple generations.
AB  - PURPOSE: To assess health, growth and reproductive success of mammals exposed for
      multiple generations to levels of radium-226 known to occur in environments
      surrounding uranium mines and mills in Canada. METHODS: The study consisted of a
      control group and four treatment groups each containing 40 mice (20 males and 20
      females) of the CBA/CaJ strain that were continuously exposed to a range of
      radium-226 levels via drinking water. Breeding was at 8-10 weeks of age and the
      study was concluded after three breeding cycles. RESULTS: When compared to
      control mice, constant consumption of drinking water containing 0.012, 0.076,
      0.78 and 8.0 Bq/l of radium-226 over four generations of mice did not
      demonstrably affect physical condition, weight, pregnancy rate, number of pups
      per litter, sex ratio and bodyweight gain of pups. Between generations, the
      observed differences in pregnancy rates that were noted in all groups, including
      controls, seemed to directly correlate with the weight and age of the females at
      breeding. CONCLUSIONS: Based on the endpoints measured on four generations of
      mice, there is no indication that the consumption of radium-226 via drinking
      water (at activity concentrations up to 8.0 Bq/l) affects health, growth and
      reproductive fitness.

PMID- 25968561
TI  - Exchange Processes in Shibasaki's Rare Earth Alkali Metal BINOLate Frameworks and
      Their Relevance in Multifunctional Asymmetric Catalysis.
AB  - Shibasaki's rare earth alkali metal BINOLate (REMB) catalysts (REMB; RE = Sc, Y,
      La - Lu; M = Li, Na, K; B = 1,1-bi-2-naphtholate; RE/M/B = 1/3/3) are among the
      most successful enantioselective catalysts and have been employed in a broad
      range of mechanistically diverse reactions. Despite the phenomenal success of
      these catalysts, several fundamental questions central to their reactivity remain
      unresolved. Combined reactivity and spectroscopic studies were undertaken to
      probe the identity of the active catalyst(s) in Lewis-acid (LA) and Lewis
      acid/Bronsted-base (LA/BB) catalyzed reactions. Exchange spectroscopy provided a
      method to obtain rates of ligand and alkali metal self-exchange in the RE/Li
      frameworks, demonstrating the utility of this technique for probing solution
      dynamics of REMB catalysts. Isolation of the first crystallographically
      characterized REMB complex with substrate bound enabled stoichiometric and
      catalytic reactivity studies, wherein we observed that substrate deprotonation by
      the catalyst framework was necessary to achieve selectivity. Our spectroscopic
      observations in LA/BB catalysis are inconsistent with previous mechanistic
      proposals, which considered only tris(BINOLate) species as active catalysts.
      These findings significantly expand our understanding of the catalyst structure
      in these privileged multifunctional frameworks and identify new directions for
      development of new catalysts. 

PMID- 25968562
TI  - Religious Allergic Contact Dermatitis.
AB  - Henna, derived from a combination of natural leaves and coloring additives, is a
      common decorative dye traditionally used in many Islamic religious celebrations.
      Para-phenylenediamine (PPD), a major component of black henna tattoo, is a strong
      sensitizer and common allergen. We report a case of severe connubial allergic
      contact dermatitis after black henna heterotransfer in a girl. 

PMID- 25968563
TI  - Impact of Pharmacotherapy on Quality of Life in Patients with Parkinson's
      Disease.
AB  - Quality of life (QoL) is a patient-reported outcome frequently included in
      Parkinson's disease (PD) clinical trials as a secondary or tertiary endpoint.
      However, QoL is an important variable that reflects the impact of disease and
      treatment from the patients' perspective. In a chronic, neurodegenerative disease
      such as PD, with a wide range of complex symptoms, QoL provides valuable and
      comprehensive information on the patients' health status. This narrative review
      aims to evaluate the effect of specific PD treatments currently in use on
      patients' QoL measured with the Parkinson's Disease Questionnaire, 39-item (PDQ
      39) or 8-item (PDQ-8) version. A quantification of this effect is provided by
      calculation of the relative change and effect size. These two parameters allow an
      intuitive standardized approach to the importance of change based on its
      magnitude. Some high-quality studies (Level I) were found for levodopa (immediate
      or extended-release formulations), levodopa with added-on catechol-O
      methyltransferase (COMT) inhibitors, levodopa/carbidopa gel for intestinal
      infusion, some dopamine agonists (ropinirole, cabergoline, pergolide), and the
      monoamine oxidase B (MAO-B) inhibitor safinamide. As a whole, these studies found
      a beneficial effect of variable magnitude, weak to moderate, on patients' QoL.
      Studies with a lower level of evidence or not providing enough data to estimate
      relative change and effect size, including those for the apomorphine subcutaneous
      pump, also reported improvement of QoL, but the evidence was insufficient to
      confirm the effect. More high-quality studies focused on QoL are needed to
      determine the real impact of PD drug treatments for this important outcome. 

PMID- 25968564
TI  - A nationwide survey of the use of plerixafor in patients with lymphoid
      malignancies who mobilize poorly demonstrates the predominant use of the "on
      demand" scheme of administration at French autologous hematopoietic stem cell
      transplant programs.
AB  - BACKGROUND: High-dose chemotherapy supported with autologous stem cell
      transplantation is a standard therapeutic option for a subset of patients with
      lymphoid malignancies. Cell procurement is nowadays done almost exclusively
      through cytapheresis, after mobilization of hematopoietic stem and progenitor
      cells (HSPCs) from the marrow to peripheral blood (PB). The egress of HSPCs out
      of hematopoietic niches occurs in various physiologic or nonhomeostatic
      situations; pharmacologic approaches include the administration of acutely
      myelosuppressive agents or hematopoietic growth factors such as recombinant human
      granulocyte-colony-stimulating factor (rHuG-CSF). The introduction of plerixafor,
      a first-of-its-class molecule that reversibly inhibits the interaction between
      the chemokine CXCL-12 (also known as SDF-1) and its receptor CXCR-4, has offered
      new opportunities for the so-called "poor mobilizers" who achieve insufficient
      mobilization and/or collection with conventional approaches. STUDY DESIGN AND
      METHODS: Because of the lack of consensus on a definition for poor mobilizers and
      the relatively high cost of plerixafor, French competent authorities have
      mandated a postmarketing survey on its use in routine practice. RESULTS AND
      CONCLUSION: We report here the results of this nationwide survey that confirms
      the clinical efficacy of plerixafor, even in the subset of patients who barely
      increased PB CD34+ cell count in response to rHuG-CSF-containing mobilization
      regimen. Furthermore, analysis of this registry showed that despite heterogeneity
      in medical practices, the early-"on-demand" or "preemptive"-introduction of
      plerixafor was widely used and did not result in an excess of prescriptions,
      beyond its expected use at the time when marketing authorization was granted.

PMID- 25968565
TI  - Can Sputum Eosinophilia Be a Constant Feature in Severe Refractory Asthmatics? A
      3-Year Longitudinal Study.
AB  - In difficult-to-treat asthmatics, uncontrolled despite a high level of therapy
      and followed for 3 years with a mean number of sputum samples/patient = 10,
      sputum eosinophilia (>=3%) was observed in 87% of all sputum samples. Persistent
      sputum eosinophilia is a characteristic of severe uncontrolled asthma.

PMID- 25968567
TI  - Deregulation of PPARbeta/delta target genes in tumor-associated macrophages by
      fatty acid ligands in the ovarian cancer microenvironment.
AB  - The nuclear receptor peroxisome proliferator-activated receptor beta/delta
      (PPARbeta/delta) is a lipid ligand-inducible transcription factor associated with
      macrophage polarization. However, its function in tumor-associated macrophages
      (TAMs) has not been investigated to date. Here, we report the PPARbeta/delta
      regulated transcriptome and cistrome for TAMs from ovarian carcinoma patients.
      Comparison with monocyte-derived macrophages shows that the vast majority of
      direct PPARbeta/delta target genes are upregulated in TAMs and largely refractory
      to synthetic agonists, but repressible by inverse agonists. Besides genes with
      metabolic functions, these include cell type-selective genes associated with
      immune regulation and tumor progression, e.g., LRP5, CD300A, MAP3K8 and ANGPTL4.
      This deregulation is not due to increased expression of PPARbeta/delta or its
      enhanced recruitment to target genes. Instead, lipidomic analysis of malignancy
      associated ascites revealed high concentrations of polyunsaturated fatty acids,
      in particular linoleic acid, acting as potent PPARbeta/delta agonists in
      macrophages. These fatty acid ligands accumulate in lipid droplets in TAMs,
      thereby providing a reservoir of PPARbeta/delta ligands. These observations
      suggest that the deregulation of PPARbeta/delta target genes by ligands of the
      tumor microenvironment contributes to the pro-tumorigenic polarization of ovarian
      carcinoma TAMs. This conclusion is supported by the association of high ANGPTL4
      expression with a shorter relapse-free survival in serous ovarian carcinoma. 

PMID- 25968568
TI  - Molecular mechanisms of human IRE1 activation through dimerization and ligand
      binding.
AB  - IRE1 transduces the unfolded protein response by splicing XBP1 through its C
      terminal cytoplasmic kinase-RNase region. IRE1 autophosphorylation is coupled to
      RNase activity through formation of a back-to-back dimer, although the
      conservation of the underlying molecular mechanism is not clear from existing
      structures. We have crystallized human IRE1 in a back-to-back conformation only
      previously seen for the yeast homologue. In our structure the kinase domain
      appears primed for catalysis but the RNase domains are disengaged. Structure
      function analysis reveals that IRE1 is autoinhibited through a Tyr-down mechanism
      related to that found in the unrelated Ser/Thr protein kinase Nek7. We have
      developed a compound that potently inhibits human IRE1 kinase activity while
      stimulating XBP1 splicing. A crystal structure of the inhibitor bound to IRE1
      shows an increased ordering of the kinase activation loop. The structures of hIRE
      in apo and ligand-bound forms are consistent with a previously proposed model of
      IRE1 regulation in which formation of a back-to-back dimer coupled to adoption of
      a kinase-active conformation drive RNase activation. The structures provide
      opportunities for structure-guided design of IRE1 inhibitors. 

PMID- 25968566
TI  - miR-29s: a family of epi-miRNAs with therapeutic implications in hematologic
      malignancies.
AB  - A wealth of studies has highlighted the biological complexity of hematologic
      malignancies and the role of dysregulated signal transduction pathways. Along
      with the crucial role of genetic abnormalities, epigenetic aberrations are
      nowadays emerging as relevant players in cancer development, and significant
      research efforts are currently focusing on mechanisms by which histone post
      translational modifications, DNA methylation and noncoding RNAs contribute to the
      pathobiology of cancer. As a consequence, these studies have provided the
      rationale for the development of epigenetic drugs, such as histone deacetylase
      inhibitors and demethylating compounds, some of which are currently in advanced
      phase of pre-clinical investigation or in clinical trials. In addition, a more
      recent body of evidence indicates that microRNAs (miRNAs) might target effectors
      of the epigenetic machinery, which are aberrantly expressed or active in cancers,
      thus reverting those epigenetic abnormalities driving tumor initiation and
      progression. This review will focus on the broad epigenetic activity triggered by
      members of the miR-29 family, which underlines the potential of miR-29s as
      candidate epi-therapeutics for the treatment of hematologic malignancies. 

PMID- 25968569
TI  - CD4+ and CD8+ T cells have opposing roles in breast cancer progression and
      outcome.
AB  - The Cancer Immunoediting concept has provided critical insights suggesting dual
      functions of immune system during the cancer initiation and development. However,
      the dynamics and roles of CD4+ and CD8+ T cells in the pathogenesis of breast
      cancer remain unclear. Here we utilized two murine breast cancer models (4T1 and
      E0771) and demonstrated that both CD4+ and CD8+ T cells were increased and
      involved in immune responses, but with distinct dynamic trends in breast cancer
      development. In addition to cell number increases, CD4+ T cells changed their
      dominant subsets from Th1 in the early stages to Treg and Th17 cells in the late
      stages of the cancer progression. We also analyzed CD4+ and CD8+ T cell
      infiltration in primary breast cancer tissues from cancer patients. We observed
      that CD8+ T cells are the key effector cell population mediating effective anti
      tumor immunity resulting in better clinical outcomes. In contrast, intra-tumoral
      CD4+ T cells have negative prognostic effects on breast cancer patient outcomes.
      These studies indicate that CD4+ and CD8+ T cells have opposing roles in breast
      cancer progression and outcomes, which provides new insights relevant for the
      development of effective cancer immunotherapeutic approaches.

PMID- 25968570
TI  - The Bacterial Component Flagellin Induces Anti-Sepsis Protection Through TLR-5,
      IL-1RN and VCAN During Polymicrobial Sepsis in Mice.
AB  - BACKGROUND: The present study was designed to observe the effects of the
      bacterial component flagellin on anti-sepsis protection through TLR-5, VCAN and
      IL-1RN. METHODS: A clinically relevant model of sepsis was induced by cecal
      ligation and puncture (CLP). An in vitro culture of endothelial cells was
      analyzed. RESULTS: Flagellin induced anti-sepsis protection through inhibition of
      inflammation and induction of endothelial proliferation by down-regulating the
      expression of TLR 3, TLR 4, and IL-1RN and promoting the expression of VCAN in
      mice 24 h post-CLP. In vitro, flagellin promoted the proliferation of endothelial
      cells. These effects could be inhibited by transfection of endothelial cells with
      VCAN siRNA or IL-1RN over-expression constructs. VCAN expression decreased after
      transfection of the cells with an IL-1RN over-expression construct and increased
      after transfection of the cells with an IL-1RN siRNA construct. IL-1RN expression
      remained unchanged after transfection of the cells with VCAN over-expression or
      siRNA constructs. CONCLUSIONS: These data suggest that flagellin pretreatment
      promoted anti-sepsis protection through the TLR-5, IL-1RN and VCAN pathway. This
      pathway is necessary to mediate endothelial repair and thereby promote survival
      following sepsis challenge.

PMID- 25968571
TI  - Detecting transmission areas of malaria parasites in a migratory bird species.
AB  - The identification of the regions where vector-borne diseases are transmitted is
      essential to study transmission patterns and to recognize future changes in
      environmental conditions that may potentially influence the transmission areas.
      SGS1, one of the lineages of Plasmodium relictum, is known to have active
      transmission in tropical Africa and temperate regions of Europe. Nuclear sequence
      data from isolates infected with SGS1 (based on merozoite surface protein 1
      (MSP1) allelic diversity) have provided new insights on the distribution and
      transmission areas of these allelic variants. For example, MSP1 alleles
      transmitted in Africa differ from those transmitted in Europe, suggesting the
      existence of two populations of SGS1 lineages. However, no study has analysed the
      distribution of African and European transmitted alleles in Afro-Palearctic
      migratory birds. With this aim, we used a highly variable molecular marker to
      investigate whether juvenile house martins become infected in Europe before their
      first migration to Africa. We explored the MSP1 allelic diversity of P. relictum
      in adult and juvenile house martins. We found that juveniles were infected with
      SGS1 during their first weeks of life, confirming active transmission of SGS1 to
      house martins in Europe. Moreover, we found that all the juveniles and most of
      adults were infected with one European transmitted MSP1 allele, whereas two adult
      birds were infected with two African transmitted MSP1 alleles. These findings
      suggest that house martins are exposed to different strains of P. relictum in
      their winter and breeding quarters. 

PMID- 25968572
TI  - A lineage-specific methylation pattern controls the transcription of the
      polycistronic mRNA coding MELOE melanoma antigens.
AB  - We recently characterized two melanoma antigens MELOE-1 and MELOE-2 derived from
      a polycistronic RNA overexpressed in the melanocytic lineage. This transcription
      profile was because of hypomethylation of the meloe proximal promoter in
      melanomas and melanocytes. Here, we investigate whether this demethylation was
      restricted to the meloe promoter or was linked to a general lack of methylation
      at the meloe locus in the melanocytic lineage. We establish the methylation
      pattern of the locus spanning more than 40 kbp, focusing on CpG islands, using
      DNA bisulfite conversion and pyrosequencing. The study was carried out on
      cultured cell lines (melanoma, melanocyte, colon cancer, and mesothelioma cell
      lines), healthy tissues (skin and colon), and melanoma tumors. Demethylation,
      specifically observed in the melanocytic lineage, involves a large promoter area
      and not the entire meloe locus. This enables updating a tight regulation of meloe
      transcription in this lineage, suggesting tissue-specific epigenetic mechanisms.
      Associated with the previously described translational mechanisms, leading to the
      specific expression of MELOE-1 and MELOE-2 in melanomas, this makes MELOE-derived
      antigens a relevant candidate for immunotherapy of melanoma. 

PMID- 25968573
TI  - Regulation of blood flow in adipose tissue: involvement of the cholinergic
      system.
AB  - Acetylcholine (Ach) has vasodilatory actions. However, data are conflicting about
      the role of Ach in regulating blood flow in subcutaneous adipose tissue (ATBF).
      This may be related to inaccurate ATBF recording or to the responder/nonresponder
      (R/NR) phenomenon. We showed previously that healthy individuals are R (ATBF
      increases postprandially by >50% of baseline BF) or NR (ATBF increases <=50%
      postprandially). Our objective was to assess the role of the cholinergic system
      on ATBF in R and NR subjects. ATBF was manipulated by in situ microinfusion of
      vasoactive agents (VA) in AT and monitored by the (133)Xenon washout technique
      (both recognized methods) at the VA site and at the control site. We tested
      incrementally increasing doses of Ach (10(-5), 10(-3), and 10(-1) mol/l; n = 15)
      and Ach receptor antagonists (Ra) before and after oral administration of 75-g
      glucose using atropine (muscarinic Ra; 10(-4) mol/l, n = 13; 10(-5) mol/l, n =
      22) and mecamylamine (nicotinic Ra; 10(-3) mol/l, n = 15; 10(-4) mol/l, n = 10).
      Compared with baseline [2.41 (1.36-2.83) ml.100 g(-1).min(-1)], Ach increased
      ATBF dose dependently [3.32 (2.80-5.09), 6.46 (4.36-9.51), and 10.31 (7.98
      11.52), P < 0.0001], with no difference between R and NR. Compared with control
      side, atropine (both concentrations) had no effect on fasting ATBF; only atropine
      10(-4) mol/l decreased post-glucose ATBF [iAUC: 1.25 (0.32-2.91) vs. 1.98 (0.64
      2.94); P = 0.04]. This effect was further apparent in R. Mecamylamine had no
      impact on fasting and postglucose ATBF in R and NR. Our results suggest that the
      cholinergic system is implicated in ATBF regulation, although it has no role in
      the blunting of ATBF response in NR.

PMID- 25968575
TI  - Ribosome biogenesis adaptation in resistance training-induced human skeletal
      muscle hypertrophy.
AB  - Resistance training (RT) has the capacity to increase skeletal muscle mass, which
      is due in part to transient increases in the rate of muscle protein synthesis
      during postexercise recovery. The role of ribosome biogenesis in supporting the
      increased muscle protein synthetic demands is not known. This study examined the
      effect of both a single acute bout of resistance exercise (RE) and a chronic RT
      program on the muscle ribosome biogenesis response. Fourteen healthy young men
      performed a single bout of RE both before and after 8 wk of chronic RT. Muscle
      cross-sectional area was increased by 6 +/- 4.5% in response to 8 wk of RT. Acute
      RE-induced activation of the ERK and mTOR pathways were similar before and after
      RT, as assessed by phosphorylation of ERK, MNK1, p70S6K, and S6 ribosomal protein
      1 h postexercise. Phosphorylation of TIF-IA was also similarly elevated following
      both RE sessions. Cyclin D1 protein levels, which appeared to be regulated at the
      translational rather than transcriptional level, were acutely increased after RE.
      UBF was the only protein found to be highly phosphorylated at rest after 8 wk of
      training. Also, muscle levels of the rRNAs, including the precursor 45S and the
      mature transcripts (28S, 18S, and 5.8S), were increased in response to RT. We
      propose that ribosome biogenesis is an important yet overlooked event in RE
      induced muscle hypertrophy that warrants further investigation.

PMID- 25968574
TI  - Additive protection by LDR and FGF21 treatment against diabetic nephropathy in
      type 2 diabetes model.
AB  - The onset of diabetic nephropathy (DN) is associated with both systemic and renal
      changes. Fibroblast growth factor (FGF)-21 prevents diabetic complications mainly
      by improving systemic metabolism. In addition, low-dose radiation (LDR) protects
      mice from DN directly by preventing renal oxidative stress and inflammation. In
      the present study, we tried to define whether the combination of FGF21 and LDR
      could further prevent DN by blocking its systemic and renal pathogeneses. To this
      end, type 2 diabetes was induced by feeding a high-fat diet for 12 wk followed by
      a single dose injection of streptozotocin. Diabetic mice were exposed to 50 mGy
      LDR every other day for 4 wk with and without 1.5 mg/kg FGF21 daily for 8 wk. The
      changes in systemic parameters, including blood glucose levels, lipid profiles,
      and insulin resistance, as well as renal pathology, were examined. Diabetic mice
      exhibited renal dysfunction and pathological abnormalities, all of which were
      prevented significantly by LDR and/or FGF21; the best effects were observed in
      the group that received the combination treatment. Our studies revealed that the
      additive renal protection conferred by the combined treatment against diabetes
      induced renal fibrosis, inflammation, and oxidative damage was associated with
      the systemic improvement of hyperglycemia, hyperlipidemia, and insulin
      resistance. These results suggest that the combination treatment with LDR and
      FGF21 prevented DN more efficiently than did either treatment alone. The
      mechanism behind these protective effects could be attributed to the suppression
      of both systemic and renal pathways.

PMID- 25968576
TI  - Femoral lipectomy increases postprandial lipemia in women.
AB  - Femoral subcutaneous adipose tissue (SAT) appears to be cardioprotective compared
      with abdominal SAT, possibly through better triglyceride (TG) sequestration. We
      hypothesized that removal of femoral SAT would increase postprandial TG through a
      reduction in dietary fatty acid (FA) storage. Normal-weight (means +/- SD; BMI
      23.9 +/- 2.6 kg/m(2)) women (n = 29; age 45 +/- 6 yr) were randomized to femoral
      lipectomy (LIPO) or control (CON) and followed for 1 yr. Regional adiposity was
      measured by DEXA and CT. A liquid meal labeled with [(14)C]oleic acid was used to
      trace the appearance of dietary FA in plasma (6-h postprandial TG), breath (24-h
      oxidation), and SAT (24-h [(14)C]TG storage). Fasting LPL activity was measured
      in abdominal and femoral SAT. DEXA leg fat mass was reduced after LIPO vs. CON
      (Delta-1.4 +/- 0.7 vs. 0.1 +/- 0.5 kg, P < 0.001) and remained reduced at 1 yr (
      1.1 +/- 1.4 vs. -0.2 +/- 0.5 kg, P < 0.05), as did CT thigh subcutaneous fat area
      (-39.6 +/- 36.6 vs. 4.7 +/- 14.6 cm(2), P < 0.05); DEXA trunk fat mass and CT
      visceral fat area were unchanged. Postprandial TG increased (5.9 +/- 7.7 vs. -0.6
      +/- 5.3 * 10(3) mg/dl, P < 0.05) and femoral SAT LPL activity decreased (-21.9 +/
      22.3 vs. 10.5 +/- 26.5 nmol.min(-1).g(-1), P < 0.05) 1 yr following LIPO vs.
      CON. There were no group differences in (14)C-labeled TG appearing in abdominal
      and femoral SAT or elsewhere. In conclusion, femoral fat remained reduced 1 yr
      following lipectomy and was accompanied by increased postprandial TG and reduced
      femoral SAT LPL activity. There were no changes in storage of meal-derived FA or
      visceral fat. Our data support a protective role for femoral adiposity on
      circulating TG independent of dietary FA storage and visceral adiposity. 

PMID- 25968579
TI  - Leukemia inhibitory factor increases glucose uptake in mouse skeletal muscle.
AB  - Members of the IL-6 family, IL-6 and ciliary neurotrophic factor (CNTF), have
      been shown to increase glucose uptake and fatty acid oxidation in skeletal
      muscle. However, the metabolic effects of another family member, leukemia
      inhibitory factor (LIF), are not well characterized. Effects of LIF on skeletal
      muscle glucose uptake and palmitate oxidation and signaling were investigated in
      ex vivo incubated mouse soleus and EDL muscles from muscle-specific AMPKalpha2
      kinase-dead, muscle-specific SOCS3 knockout, and lean and high-fat-fed mice.
      Inhibitors were used to investigate involvement of specific signaling pathways.
      LIF increased muscle glucose uptake in dose (50-5,000 pM/l) and time-dependent
      manners with maximal effects at the 30-min time point. LIF increased Akt Ser(473)
      phosphorylation (P) in soleus and EDL, whereas AMPK Thr(172) P was unaffected.
      Incubation with parthenolide abolished LIF-induced glucose uptake and STAT3
      Tyr(705) P, whereas incubation with LY-294002 and wortmannin suppressed both
      basal and LIF-induced glucose uptake and Akt Ser(473) P, indicating that JAK and
      PI 3-kinase signaling is required for LIF-stimulated glucose uptake. Incubation
      with rapamycin and AZD8055 indicated that mammalian target of rapamycin complex
      (mTORC)2, but not mTORC1, also is required for LIF-stimulated glucose uptake. In
      contrast to CNTF, LIF stimulation did not alter palmitate oxidation. LIF
      stimulated glucose uptake was maintained in EDL from obese insulin-resistant
      mice, whereas soleus developed LIF resistance. Lack of SOCS3 and AMPKalpha2 did
      not affect LIF-stimulated glucose uptake. In conclusion, LIF acutely increased
      muscle glucose uptake by a mechanism potentially involving the PI 3
      kinase/mTORC2/Akt pathway and is not impaired in EDL muscle from obese insulin
      resistant mice. 

PMID- 25968577
TI  - Effects of aging, exercise, and disease on force transfer in skeletal muscle.
AB  - The loss of muscle strength and increased injury rate in aging skeletal muscle
      has previously been attributed to loss of muscle protein (cross-sectional area)
      and/or decreased neural activation. However, it is becoming clear that force
      transfer within and between fibers plays a significant role in this process as
      well. Force transfer involves a secondary matrix of proteins that align and
      transmit the force produced by the thick and thin filaments along muscle fibers
      and out to the extracellular matrix. These specialized networks of cytoskeletal
      proteins aid in passing force through the muscle and also serve to protect
      individual fibers from injury. This review discusses the cytoskeleton proteins
      that have been identified as playing a role in muscle force transmission, both
      longitudinally and laterally, and where possible highlights how disease, aging,
      and exercise influence the expression and function of these proteins.

PMID- 25968578
TI  - MyD88 regulates physical inactivity-induced skeletal muscle inflammation,
      ceramide biosynthesis signaling, and glucose intolerance.
AB  - Physical inactivity in older adults is a risk factor for developing glucose
      intolerance and impaired skeletal muscle function. Elevated inflammation and
      ceramide biosynthesis have been implicated in metabolic disruption and are linked
      to Toll-like receptor (TLR)/myeloid differentiation primary response 88 (MyD88)
      signaling. We hypothesize that a physical inactivity stimulus, capable of
      inducing glucose intolerance, would increase skeletal muscle inflammation and
      ceramide biosynthesis signaling and that this response would be regulated by the
      TLR/MyD88 pathway. Therefore, we subjected wild-type (WT) and MyD88(-/-) mice to
      hindlimb unloading (HU) for 14 days or an ambulatory control period. We observed
      impaired glucose uptake, muscle insulin signaling (p-Akt), and increased markers
      of NF-kappaB signaling (p-IkappaBalpha), inflammation (p-JNK, IL-6), TLR4, and
      the rate-limiting enzyme of ceramide biosynthesis, SPT2, with HU WT (P < 0.05),
      but not in HU MyD88(-/-) mice. Concurrently, we found that 5 days of bed rest in
      older adults resulted in whole body glucose dysregulation, impaired skeletal
      muscle insulin signaling, and upregulation of muscle IL-6 and SPT2 (P < 0.05).
      Post-bed rest TLR4 abundance was tightly correlated with impaired postprandial
      insulin and glucose levels. In conclusion, MyD88 signaling is necessary for the
      increased inflammation, ceramide biosynthesis signaling, and compromised
      metabolic function that accompanies physical inactivity.

PMID- 25968581
TI  - Sigillin A, a unique polychlorinated arthropod deterrent from the snow flea
      Ceratophysella sigillata.
AB  - The snow flea Ceratophysella sigillata, a winter-active species of springtail,
      produces unique polychlorinated octahydroisocoumarins to repel predators. The
      structure of the major compound, sigillin A, was elucidated through isolation,
      spectroscopic analysis, and X-ray crystallography. Sigillin A showed high
      repellent activity in a bioassay with predatory ants. A promising approach for
      the total synthesis of members of this new class of natural compounds was also
      developed. 

PMID- 25968580
TI  - Uterine artery dysfunction in pregnant ACE2 knockout mice is associated with
      placental hypoxia and reduced umbilical blood flow velocity.
AB  - Angiotensin-converting enzyme 2 (ACE2) knockout is associated with reduced fetal
      weight at late gestation; however, whether uteroplacental vascular and/or
      hemodynamic disturbances underlie this growth-restricted phenotype is unknown.
      Uterine artery reactivity and flow velocities, umbilical flow velocities,
      trophoblast invasion, and placental hypoxia were determined in ACE2 knockout (KO)
      and C57Bl/6 wild-type (WT) mice at day 14 of gestation. Although systolic blood
      pressure was higher in pregnant ACE2 KO vs. WT mice (102.3 +/- 5.1 vs. 85.1 +/-
      1.9 mmHg, n = 5-6), the magnitude of difference was similar to that observed in
      nonpregnant ACE2 KO vs. WT mice. Maternal urinary protein excretion, serum
      creatinine, and kidney or heart weights were not different in ACE2 KO vs. WT.
      Fetal weight and pup-to-placental weight ratio were lower in ACE2 KO vs. WT mice.
      A higher sensitivity to Ang II [pD2 8.64 +/- 0.04 vs. 8.5 +/- 0.03 (-log EC50)]
      and greater maximal contraction to phenylephrine (169.0 +/- 9.0 vs. 139.0 +/-
      7.0% KMAX), were associated with lower immunostaining for Ang II receptor 2 and
      fibrinoid content of the uterine artery in ACE2 KO mice. Uterine artery flow
      velocities and trophoblast invasion were similar between study groups. In
      contrast, umbilical artery peak systolic velocities (60.2 +/- 4.5 vs. 75.1 +/-
      4.5 mm/s) and the resistance index measured using VEVO 2100 ultrasound were lower
      in the ACE2 KO vs. WT mice. Immunostaining for pimonidazole, a marker of hypoxia,
      and hypoxia-inducible factor-2alpha were higher in the trophospongium and
      placental labyrinth of the ACE2 KO vs. WT. In summary, placental hypoxia and
      uterine artery dysfunction develop before major growth of the fetus occurs and
      may explain the fetal growth restricted phenotype. 

PMID- 25968582
TI  - Successful Mercaptopurine Usage despite Azathioprine-Induced Pancreatitis in
      Paediatric Crohn's Disease.
AB  - BACKGROUND: Azathioprine [AZA] and mercaptopurine [MP] are recommended for
      maintenance of steroid-free remission in children with Crohn's disease [CD].
      Azathioprine-induced pancreatitis, an idiosyncratic and major side effect, has
      been considered as an absolute contraindication for the use of a second
      thiopurine in IBD patients. MATERIALS AND METHODS: We describe two children with
      CD in whom MP were successfully trialled after a confirmed azathioprine-induced
      pancreatitis, being well tolerated in both cases. RESULTS: Two boys [13 and 10
      years old] started exclusive enteral nutrition after diagnosis of moderate
      (Pediatric Crohn's Disease Activity Index [wPCDAI] = 45) and mild [wPCDAI = 35]
      CD. Both developed an acute mild to moderate pancreatitis after 2 and 3 weeks,
      respectively, of AZA treatment but recovered fully in hospital after AZA
      withdrawal. They started on MP treatment without any adverse effect. They were
      tested for the presence of polymorphisms 238G>C, 460G>A, and 719A>G in the TPMT
      gene and 94C>A and 21>C in the ITPase. Both patients were wild-type for all
      tested polymorphisms. CONCLUSIONS: Azathioprine-induced acute pancreatitis should
      not be considered as an absolute contraindication for the use of MP. Further
      investigation is required to create a better understanding of the mechanism
      underlying the adverse events and to allow more possibilities for personalised
      therapy.

PMID- 25968583
TI  - Rediscovery of the Anti-Pancreatic Antibodies and Evaluation of their Prognostic
      Value in a Prospective Clinical Cohort of Crohn's Patients: The Importance of
      Specific Target Antigens [GP2 and CUZD1].
AB  - BACKGROUNDS: Glycoprotein 2[GP2] and CUB zona pellucida-like domain 1[CUZD1]
      belong to protein families involved in gut innate immunity processes and have
      recently been identified as specific targets of anti-pancreatic autoantibodies
      [PAbs] in Crohn's disease[CD]. We aimed to determine the prognostic potential of
      novel target-specific PAbs regarding long-term disease course of an adult CD
      patient cohort. METHODS: Sera of 458 consecutive well-characterised IBD patients
      from a single referral IBD centre were tested by enzyme-linked immunosorbent
      assay [ELISA] with isoform 4 of recombinant GP2 [anti-MZGP2 and anti-GP2 IgA/IgG]
      and indirect immunofluorescence test [IIFT] system with GP2 and CUZD1 expressing
      transfected HEK 293 cells [anti-rPAg2 and rPAg1 IgA/IgG]. Clinical data were
      available on complicated disease or surgical interventions as well as disease
      activity and medical treatment during the prospective follow-up [median, 108
      months]. RESULTS: Totals of 12.4% and 20.8% of CD patients were positive for
      IgA/IgG type of anti-GP2 and anti-CUZD1, respectively, with a significant
      difference compared with UC [p < 0.01]. Antibody status was stable over time.
      Agreement among three different anti-GP2 assays was good. Positivity for PAbs,
      mainly IgA subtypes, predicted a faster progression towards complicated disease
      course. In Kaplan-Meier analysis, time to surgery or development of perianal
      disease was associated with anti-GP2 IgA [pLogRank < 0.01] or anti-CUZD1 IgA
      [pLogRank < 0.001] positivity, respectively. Anti-CUZD1 IgA remained an
      independent predictor in the multivariate Cox-regression model (hazard ratio
      [HR]: 3.43, 95% confidence interval [CI]: 1.68-7.02, p < 0.001). CONCLUSIONS: The
      present study has shown that specific PAbs [especially IgA subtype] predict
      complicated disease course including the development of perianal disease in CD.

PMID- 25968584
TI  - Body Mass Index and Smoking Affect Thioguanine Nucleotide Levels in Inflammatory
      Bowel Disease.
AB  - INTRODUCTION: Optimal levels of the thiopurine metabolite, 6-thioguanine
      nucleotides [6-TGN] correlate with remission of inflammatory bowel disease [IBD].
      Apart from variations in the thiopurine methyl transferase [TPMT] gene, little is
      known about other predictors of 6-TGN levels. Obesity adversely affects response
      to infliximab and adalimumab and clinical course in IBD, but little is known
      about the interaction of thiopurines and obesity. We investigated the
      relationship between body mass index [BMI] and 6-TGN levels and sought to examine
      other predictors of 6-TGN levels. METHODS: This retrospective cohort study
      included patients with concurrent measurements of 6-TGN and BMI. The association
      between 6-TGN and clinical variables including BMI was estimated using a
      multivariable linear regression model. RESULTS: Of 132 observations, 77 [58%] had
      Crohn's disease and 55 [42%] ulcerative colitis. BMI, smoking, and TPMT levels
      were associated with 6-TGN levels in multivariable analysis. Every 5kg/m(2)
      increase in BMI was associated with an 8% decrease in 6-TGN (0.92; 95% confidence
      interval [CI] 0.87-0.98; p = 0.009). Smokers had higher 6-TGN levels in
      comparison with non-/ex-smokers [1.43; 95% CI 1.02-2.02; p = 0.041]. Patients
      with intermediate TPMT had higher 6-TGN compared to those with normal levels
      [2.13; 95% CI 1.62-2.80; p < 0.001]. Obese patients were more likely to have sub
      therapeutic 6-TGN levels and a higher methyl mercaptopurine nucleotide [MMPN/TGN]
      ratio despite a similar dose of thiopurines. CONCLUSIONS: Active smoking and
      intermediate TPMT values were associated with higher 6-TGN levels but increasing
      BMI resulted in lower 6-TGN and higher MMPN levels. This may explain the worse
      outcome that has been reported previously in obese IBD subjects.

PMID- 25968585
TI  - Changes in cytokine profile may predict therapeutic efficacy of infliximab in
      patients with ulcerative colitis.
AB  - BACKGROUND AND AIM: Infliximab is an established therapy for ulcerative colitis
      (UC). The aim of this study was to examine various serum cytokine levels and to
      identify possible markers predictive of therapeutic efficacy of infliximab for UC
      patients. METHODS: Twenty-one patients with moderately active UC were given
      intravenous infliximab (5 mg/kg) at 0, 2, and 6 weeks as induction therapy. The
      serum levels of 17 cytokines were determined using a Bio-Plex suspension array
      system before and 8 weeks after induction therapy. Partial Mayo score (PMS) and
      serum C-reactive protein levels were used for the determination of clinical
      activities at 0 and 8 weeks after the treatment. The overall therapeutic effect
      was determined at 26 weeks according to the PMS. RESULTS: The median value of the
      PMS decreased significantly 8 weeks after the treatment (from 6 to 1.5, P <
      0.05). However, C-reactive protein levels did not change significantly. Levels of
      serum interleukin (IL)-8 (P < 0.05) and macrophage inflammatory protein-1beta (P
      < 0.005) significantly decreased 8 weeks after the induction. Serum levels of the
      other 15 cytokines did not change significantly. At 26 weeks, 13 of 20 patients
      (65%) were responders while 7 patients were non-responders. Levels of serum IL-6
      at 8 weeks were significantly lower in responders than in non-responders (P <
      0.05). CONCLUSIONS: Serum IL-8 and macrophage inflammatory protein-1beta seem to
      be sensitive markers for UC patients treated with infliximab, while IL-6 at 8
      weeks after induction therapy may be predictive of subsequent response to
      infliximab.

PMID- 25968586
TI  - Integrating paid work and chronic illness in daily life: A space-time approach to
      understanding the challenges.
AB  - The upward trend of chronic illness in working age populations calls for better
      understanding of the difficulties chronically ill people face with workforce
      participation. Existing research focuses primarily on physical limitations and
      employer attitudes about chronic illness. Here we use a space-time approach to
      illuminate the importance of negotiating logistical challenges and embodied
      rhythms when balancing work and chronic illness. We draw from time geography and
      rhythmanalysis in analysing interviews from a qualitative case study of 26
      individuals living with chronic kidney disease in Australia. Difficulties with
      paid work arise from: (1) competition for space-time resources by employers and
      health services; (2) arrhythmias between the body, work and health services; and
      (3) the absence of workplace rhythms on which to 'hook' health activities.
      Implications for workplaces and health services design are discussed. 

PMID- 25968587
TI  - Dysmorphologic assessment in 115 Mayer-Rokitansky-Kuster-Hauser patients.
AB  - Mayer-Rokitansky-Kuster-Hauser (MRKH) patients are characterized by congenital
      aplasia of the uterus and the upper part of the vagina, with normal secondary
      sexual characteristics. This disorders affects one in 4000-5000 females and it is
      classified as typical, type I or isolated, and as atypical, type II, manifesting
      additional malformations. To date, no specific study has addressed the question
      of facial features in MRKH patients. The aim of this study is to perform a
      dysmorphological assessment of a large cohort of patients. We studied 115 women
      referred to our center from 2008 to 2012. Seventy-two percentage (83/115) of our
      patients showed isolated uterovaginal aplasia (MRKH type I); 32/115 (28%) had
      other abnormalities including kidney and cardiac defects, skeletal anomalies, and
      hearing impairment. Auxologic investigations comprised measurements of height,
      weight, BMI, head circumference, arm span, span to height ratio, hand length,
      middle finger length, foot length, inner and outer intercanthal distance, and
      auricle length. All patients had normal measurements, except for the outer
      canthal distance-inner canthal distance ratio, which was consistent with
      elongated eyelids. Women with MRKH syndromes do not present a typical facial
      feature and a dysmorphological examination of all patients seems unnecessary.
      However, a multidisciplinary approach is useful with respect to explaining the
      etiology, interpreting test results, and counseling. 

PMID- 25968588
TI  - Left chest wall deformity, dextrocardia, and diaphragmatic hernia: a variant of
      Poland or new syndrome?

PMID- 25968589
TI  - Early identification of ADHD risk via infant temperament and emotion regulation:
      a pilot study.
AB  - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is theorized to have
      temperamental precursors early in life. These are difficult to identify because
      many core features of ADHD, such as breakdowns in executive function and self
      control, involve psychological and neural systems that are too immature to
      reliably show dysfunction in early life. ADHD also involves emotional
      dysregulation, and these temperamental features appear earlier as well. Here, we
      report a first attempt to utilize indices of emotional regulation to identify
      ADHD-related liability in infancy. METHODS: Fifty women were recruited in the 2nd
      trimester of pregnancy, with overselection for high parental ADHD symptoms.
      Measures of maternal body mass index, nutrition, substance use, stress, and mood
      were examined during pregnancy as potential confounds. Offspring were evaluated
      at 6 months of age using LABTAB procedures designed to elicit fear, anger, and
      regulatory behavior. Mothers completed the Infant Behavior Questionnaire about
      their child's temperament. RESULTS: After control for associated covariates,
      including maternal depression and prenatal stress, family history of ADHD was
      associated with measures of anger/irritability, including infant negative
      vocalizations during the arm restraint task (p = .004), and maternal ratings of
      infant distress to limitations (p = .036). In the regulation domain, familial
      ADHD was associated with less parent-oriented attention seeking during the still
      face procedure (p < .001), but this was not echoed in the maternal ratings of
      recovery from distress. CONCLUSIONS: Affective response at 6 months of age may
      identify infants with familial history of ADHD, providing an early indicator of
      ADHD liability. These preliminary results provide a foundation for further
      studies and will be amplified by enlarging this cohort and following participants
      longitudinally to evaluate ADHD outcomes.

PMID- 25968590
TI  - Neurologic outcome of urea cycle disorder liver transplant recipients may be
      predicted by pretransplant neurological imaging.
AB  - Liver transplantation treats the hepatic affectation of UCDs; however,
      irreversible neurologic damage pretransplant is difficult to assess providing
      transplant teams with ethical dilemmas for liver transplantation. The purpose of
      our study was to determine whether pretransplant neuroimaging can predict
      developmental outcomes post-liver-transplant in children with UCDs. METHODS:
      Patients undergoing liver transplantation for UCDs at Cincinnati Children's
      Hospital Medical Center between 2002 and 2012 were identified. Neurologic
      assessments prior to and after transplantation were categorized into mild,
      moderate, or severe disability. Neuroimaging data were categorized into mild,
      moderate, or severe by a single pediatric neuroradiologist. RESULTS: Fifteen
      patients were identified of whom eight had neuroimaging prior to transplantation.
      Of the eight patients that had neuroimaging, four were categorized as severe, one
      moderate, and three no-to-mild delay. All four patients whose imaging was severe
      were found to have moderate-to-severe neurologic delay. Of the three patients
      with no-to-mild changes on neuroimaging two of three were found to have no-to
      mild delay on developmental assessments after transplantation. CONCLUSION:
      Neuroimaging may be a helpful tool in determining developmental prognosis and
      outcomes post-liver-transplantation for UCDs. Further studies maybe needed to
      validate our preliminary findings.

PMID- 25968591
TI  - Cell toxicity of 2-hydroxyethyl methacrylate (HEMA): the role of oxidative
      stress.
AB  - 2-Hydroxyethyl methacrylate (HEMA) is a methacrylate monomer used in polymer
      based dental-restorative materials. In this study, the viability of human lung
      epithelial cells, BEAS-2B, was investigated after exposure to this monomer.
      Exposure to HEMA reduced the viability of the BEAS-2B cells as a result of
      increased apoptosis, interruption of the cell cycle, and decreased cell
      proliferation. Depletion of cellular glutathione and increased levels of reactive
      oxygen species (ROS) were seen after exposure of BEAS-2B cells to HEMA. The
      glutathione synthase inhibitor, L-buthioninesulfoximine (BSO), was used to study
      whether the reduced viability was caused by glutathione depletion and increased
      levels of ROS. Similarly to incubation with HEMA, incubation with BSO resulted in
      glutathione depletion and increased ROS levels, without increasing cell death or
      inhibiting cell growth. The results indicate that HEMA-induced cell damage is not
      caused exclusively by these mechanisms. Mechanisms other than glutathione
      depletion and ROS formation seem to be of importance for the toxic effect of HEMA
      on lung epithelial cells. 

PMID- 25968592
TI  - The Aldosterone/Renin Ratio as a Diagnostic Tool for the Diagnosis of Primary
      Hypoaldosteronism in Newborns and Infants.
AB  - BACKGROUND/AIMS: Primary hypoaldosteronism is a rare inborn disorder with life
      threatening symptoms in newborns and infants due to an aldosterone synthase
      defect. Diagnosis is often difficult as the plasma aldosterone concentration
      (PAC) can remain within the normal range and thus lead to misinterpretation and
      delayed initiation of life-saving therapy. We aimed to test the eligibility of
      the PAC/plasma renin concentration (PRC) ratio as a tool for the diagnosis of
      primary hypoaldosteronism in newborns and infants. Meth ods: Data of 9 patients
      aged 15 days to 12 months at the time of diagnosis were collected. The diagnosis
      of primary hypoaldosteronism was based on clinical and laboratory findings over a
      period of 12 years in 3 different centers in Switzerland. To enable a valid
      comparison, the values of PAC and PRC were correlated to reference methods.
      RESULTS: In 6 patients, the PAC/PRC ratio could be determined and showed
      constantly decreased values <1 (pmol/l)/(mU/l). In 2 patients, renin was noted as
      plasma renin activity (PRA). PAC/PRA ratios were also clearly decreased. The
      diagnosis was subsequently genetically confirmed in 8 patients. CONCLUSION: A
      PAC/PRC ratio <1 pmol/mU and a PAC/PRA ratio <28 (pmol/l)/(ng/ml * h) are
      reliable tools to identify primary hypoaldosteronism in newborns and infants and
      help to diagnose this life-threatening disease faster.

PMID- 25968593
TI  - Mid-regional pro-atrial natriuretic peptide and blood pressure in adolescents:
      effect of gender and pubertal stage.
AB  - Little is known about blood pressure in relation to circulating natriuretic
      peptide concentrations and gender in generally healthy adolescents. We studied 15
      year-old females and males (n = 335) from the Danish site of the European Youth
      Heart Study (EYHS). Blood pressure was measured using a standardized protocol,
      sexual maturity was assessed according to Tanner stage, and as a surrogate for
      atrial natriuretic peptide, we measured mid-regional pro-atrial natriuretic
      peptide (MR-proANP) in plasma. Compared with boys, girls had lower systolic blood
      pressure (SBP) (mean +/- SD: 109.6 +/- 9.9 mmHg vs 116.9 +/- 11.4 mmHg, p <
      0.0001) and higher plasma MR-proANP concentrations [median (interquartile range):
      42.1 pmol/l (31.9-50.2 pmol/l) vs 36.6 pmol/l (30.6-44.9 pmol/l), p = 0.0046].
      When female adolescents were further subdivided according to Tanner stage, there
      were no differences in blood pressure and plasma MR-proANP concentrations between
      post-pubertal and pubertal girls (p > 0.17). In contrast, after similar
      subdivision, post-pubertal boys had higher SBP (mean +/- SD: 117.7 +/- 11.7 mmHg
      vs 111.4 +/- 7.9 mmHg, p = 0.029) and lower plasma MR-proANP concentrations
      [median (interquartile range): 36.2 pmol/l (30.6-43.1 pmol/l) vs 46.4 pmol/l
      (30.3-51.1 pmol/l), p = 0.043] compared with pubertal boys. Given their higher
      SBP, boys had lower than expected plasma concentrations of MR-proANP compared
      with girls, and given their higher SBP, post-pubertal boys had lower than
      expected plasma concentrations of MR-proANP compared with pubertal boys.

PMID- 25968594
TI  - Functional Characterization and Comparison of Intercellular Communication in Stem
      Cell-Derived Cardiomyocytes.
AB  - One novel treatment strategy for the diseased heart focuses on the use of
      pluripotent stem cell-derived cardiomyocytes (SC-CMs) to overcome the heart's
      innate deficiency for self-repair. However, targeted application of SC-CMs
      requires in-depth characterization of their true cardiogenic potential in terms
      of excitability and intercellular coupling at cellular level and in multicellular
      preparations. In this study, we elucidated the electrical characteristics of
      single SC-CMs and intercellular coupling quality of cell pairs, and concomitantly
      compared them with well-characterized murine native neonatal and immortalized HL
      1 cardiomyocytes. Firstly, we investigated the electrical properties and Ca(2+)
      signaling mechanisms specific to cardiac contraction in single SC-CMs. Despite
      heterogeneity of the new cardiac cell population, their electrophysiological
      activity and Ca(2+) handling were similar to native cells. Secondly, we
      investigated the capability of paired SC-CMs to form an adequate subunit of a
      functional syncytium and analyzed gap junctions and signal transmission by dye
      transfer in cell pairs. We discovered significantly diminished coupling in SC-CMs
      compared with native cells, which could not be enhanced by a coculture approach
      combining SC-CMs and primary CMs. Moreover, quantitative and structural analysis
      of gap junctions presented significantly reduced connexin expression levels
      compared with native CMs. Strong dependence of intercellular coupling on gap
      junction density was further confirmed by computational simulations. These novel
      findings demonstrate that despite the cardiogenic electrophysiological profile,
      SC-CMs present significant limitations in intercellular communication. Inadequate
      coupling may severely impair functional integration and signal transmission,
      which needs to be carefully considered for the prospective use of SC-CMs in
      cardiac repair. Stem Cells 2015;33:2208-2218. 

PMID- 25968595
TI  - (R)-alpha-trifluoromethylalanine containing short peptide in the inhibition of
      amyloid peptide fibrillation.
AB  - The extracellular deposition of insoluble amyloid fibrils resulting from the
      aggregation of the amyloid-beta (Abeta) is a pathological feature of neuronal
      loss in Alzheimer's disease (AD). Numerous small molecules have been reported to
      interfere with the process of Abeta aggregation. Compounds containing aromatic
      structures, hydrophobic amino acids and/or the alpha-aminoisobutyric acid (Aib)
      as beta-sheet breaker elements have been reported to be effective inhibitors of
      Abeta aggregation. We synthesized two peptides, one containing the Aib amino acid
      and the other including its trifluoromethylated analog (R)-alpha
      Trifluoromethylalanine ((R)-Tfm-Alanine) and we evaluated the impact of these
      peptides on Abeta amyloid formation. The compounds were tested by standard
      methods such as thioflavin-T fluorescence spectroscopy and transmission electron
      microscopy but also by circular dichroism, liquid state nuclear magnetic
      resonance (NMR) and NMR saturation transfer difference (STD) experiments to
      further characterize the effect of the two molecules on Abeta structure and on
      the kinetics of depletion of monomeric, soluble Abeta. Our results demonstrate
      that the peptide containing Aib reduces the quantity of aggregates containing
      beta-sheet structure but slightly inhibits Abeta fibril formation, while the
      molecule including the trifluoromethyl (Tfm) group slows down the kinetics of
      Abeta fibril formation, delays the random coil to beta-sheet structure transition
      and induces a change in the oligomerization pathway. These results suggest that
      the hydrophobic Tfm group has a better affinity with Abeta than the methyl groups
      of the Aib and that this Tfm group is effective and important in preventing the
      Abeta aggregation.

PMID- 25968596
TI  - Imidacloprid impairs the post-embryonic development of the midgut in the yellow
      fever mosquito Stegomyia aegypti (=Aedes aegypti).
AB  - The mosquito Stegomyia aegypti (=Aedes aegypti) (Diptera: Culicidae) is a vector
      for the dengue and yellow fever viruses. As blood digestion occurs in the midgut,
      this organ constitutes the route of entry of many pathogens. The effects of the
      insecticide imidacloprid on the survival of St. aegypti were investigated and the
      sub-lethal effects of the insecticide on midgut development were determined.
      Third instar larvae were exposed to different concentrations of imidacloprid
      (0.15, 1.5, 3.0, 6.0 and 15.0 p.p.m.) and survival was monitored every 24 h for
      10 days. Midguts from imidacloprid-treated insects at different stages of
      development were dissected and processed for analyses by transmission electron
      microscopy, immunofluorescence microscopy and terminal deoxynucleotidyl
      transferase dUTP nick-end labelling (TUNEL) assays. Imidacloprid concentrations
      of 3.0 and 15.0 p.p.m. were found to affect midgut development similarly.
      Digestive cells of the fourth instar larvae (L4) midgut exposed to imidacloprid
      had more multilamellar bodies, abundantly found in the cell apex, and more
      electron-lucent vacuoles in the basal region compared with those from untreated
      insects. Moreover, imidacloprid interfered with the differentiation of
      regenerative cells, dramatically reducing the number of digestive and endocrine
      cells and leading to malformation of the midgut epithelium in adults. The data
      demonstrate that imidacloprid can reduce the survival of mosquitoes and thus
      indicate its potentially high efficacy in the control of St. aegypti populations.

PMID- 25968597
TI  - Synthesis of Nanoporous Ni-Co Mixed Oxides by Thermal Decomposition of Metal
      Cyanide Coordination Polymers.
AB  - A straightforward strategy to prepare nanoporous metal oxides with well-defined
      shapes is highly desirable. Through thermal treatment and a proper selection of
      metal-cyanide coordination polymers, nanoporous nickel-cobalt mixed oxides with
      different shapes (i.e., flakes and cubes) can be easily prepared. Our nanoporous
      materials demonstrate high electrocatalytic activity for oxygen evolution
      reaction. 

PMID- 25968598
TI  - Effect of Sulforaphane in Men with Biochemical Recurrence after Radical
      Prostatectomy.
AB  - Increases in serum levels of prostate-specific antigen (PSA) occur commonly in
      prostate cancer after radical prostatectomy and are designated "biochemical
      recurrence." Because the phytochemical sulforaphane has been studied extensively
      as an anticancer agent, we performed a double-blinded, randomized, placebo
      controlled multicenter trial with sulforaphane in 78 patients (mean age, 69 +/- 6
      years) with increasing PSA levels after radical prostatectomy. Treatment
      comprised daily oral administration of 60 mg of a stabilized free sulforaphane
      for 6 months (M0-M6) followed by 2 months without treatment (M6-M8). The study
      was designed to detect a 0.012 log (ng/mL)/month decrease in the log PSA slope in
      the sulforaphane group from M0 to M6. The primary endpoint was not reached. For
      secondary endpoints, median log PSA slopes were consistently lower in
      sulforaphane-treated men. Mean changes in PSA levels between M6 and M0 were
      significantly lower in the sulforaphane group (+0.099 +/- 0.341 ng/mL) than in
      placebo (+0.620 +/- 1.417 ng/mL; P = 0.0433). PSA doubling time was 86% longer in
      the sulforaphane than in the placebo group (28.9 and 15.5 months, respectively).
      PSA increases >20% at M6 were significantly greater in the placebo group (71.8%)
      than in the sulforaphane group (44.4%); P = 0.0163. Compliance and tolerance were
      very good. Sulforaphane effects were prominent after 3 months of intervention (M3
      M6). After treatment, PSA slopes from M6 to M8 remained the same in the 2 arms.
      Daily administration of free sulforaphane shows promise in managing biochemical
      recurrences in prostate cancer after radical prostatectomy.

PMID- 25968599
TI  - A cluster-randomised controlled trial to assess the effectiveness and cost
      effectiveness of a childhood obesity prevention programme delivered through
      schools, targeting 6-7 year old children: the WAVES study protocol.
AB  - BACKGROUND: There is some evidence that school-based interventions are effective
      in preventing childhood obesity. However, longer term outcomes, equity of effects
      and cost-effectiveness of interventions have not been assessed. The aim of this
      trial is to assess the clinical and cost-effectiveness of a multi-component
      intervention programme targeting the school and family environment through
      primary schools, in preventing obesity in 6-7 year old children, compared to
      usual practice. METHODS: This cluster randomised controlled trial is set in 54
      primary schools within the West Midlands, UK, including a multi-ethnic,
      socioeconomically diverse population of children aged 6-7 years. The 12-month
      intervention consists of healthy diet and physical activity promotion. These
      include: activities to increase time spent doing physical activity within the
      school day, participation in the 'Villa Vitality' programme (a programme that is
      delivered by an iconic sporting institution (Aston Villa Football Club), which
      provides interactive learning opportunities for physical activity and healthy
      eating), healthy cooking skills workshops in school time for parents and
      children, and provision of information to families signposting local leisure
      opportunities. The primary (clinical) outcome is the difference in body mass
      index (BMI) z-scores between arms at 3 and 18 months post-intervention
      completion. Cost per Quality Adjusted Life Year (QALY) will also be assessed. The
      sample size estimate (1000 children split across 50 schools at follow-up) is
      based on 90% power to detect differences in BMI z-score of 0.25 (estimated ICC <=
      0.04), assuming a correlation between baseline and follow-up BMI z-score of 0.9.
      Treatment effects will be examined using mixed model ANCOVA. Primary analysis
      will adjust for baseline BMI z-score, and secondary analysis will adjust for pre
      specified baseline school and child level covariates. DISCUSSION: The West
      Midlands ActiVe lifestyle and healthy Eating in School children (WAVES) study is
      the first trial that will examine the cost-effectiveness and long term outcomes
      of a childhood obesity prevention programme in a multi-ethnic population, with a
      sufficient sample size to detect clinically important differences in adiposity.
      The intervention was developed using the Medical Research Council framework for
      complex interventions, and outcomes are measured objectively, together with a
      comprehensive process evaluation. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN97000586 (registered May 2010).

PMID- 25968601
TI  - A collection of cytochrome P450 monooxygenase genes involved in modification and
      detoxification of herbicide atrazine in rice (Oryza sativa) plants.
AB  - Plant cytochrome P450 monooxygenases constitute one of the largest families of
      protein genes involved in plant growth, development and acclimation to biotic and
      abiotic stresses. However, whether these genes respond to organic toxic compounds
      and their biological functions for detoxifying toxic compounds such as herbicides
      in rice are poorly understood. The present study identified 201 genes encoding
      cytochrome P450s from an atrazine-exposed rice transcriptome through high
      throughput sequencing. Of these, 69 cytochrome P450 genes were validated by
      microarray and some of them were confirmed by real time PCR. Activities of NADPH
      cytochrome P450 reductase (CPR) and p-nitroanisole O-demethylase (PNOD) related
      to toxicity were determined and significantly induced by atrazine exposure. To
      dissect the mechanism underlying atrazine modification and detoxification by
      P450, metabolites (or derivatives) of atrazine in plants were analyzed by ultra
      performance liquid chromatography mass spectrometry (UPLC/MS). Major metabolites
      comprised desmethylatrazine (DMA), desethylatrazine (DEA), desisopropylatrazine
      (DIA), hydroxyatrazine (HA), hydroxyethylatrazine (HEA) and
      hydroxyisopropylatrazine (HIA). All of them were chemically modified by P450s.
      Furthermore, two specific inhibitors of piperonyl butoxide (PBO) and malathion
      (MAL) were used to assess the correlation between the P450s activity and rice
      responses including accumulation of atrazine in tissues, shoot and root growth
      and detoxification. 

PMID- 25968600
TI  - Signatures of positive selection in the cis-regulatory sequences of the human
      oxytocin receptor (OXTR) and arginine vasopressin receptor 1a (AVPR1A) genes.
AB  - BACKGROUND: The evolutionary highly conserved neurohypophyseal hormones oxytocin
      and arginine vasopressin play key roles in regulating social cognition and
      behaviours. The effects of these two peptides are meditated by their specific
      receptors, which are encoded by the oxytocin receptor (OXTR) and arginine
      vasopressin receptor 1a genes (AVPR1A), respectively. In several species,
      polymorphisms in these genes have been linked to various behavioural traits.
      Little, however, is known about whether positive selection acts on sequence
      variants in genes influencing variation in human behaviours. RESULTS: We
      identified, in both neuroreceptor genes, signatures of balancing selection in the
      cis-regulative acting sequences such as transcription factor binding and enhancer
      sequences, as well as in a transcriptional repressor sequence motif.
      Additionally, in the intron 3 of the OXTR gene, the SNP rs59190448 appears to be
      under positive directional selection. For rs59190448, only one phenotypical
      association is known so far, but it is in high LD' (>0.8) with loci of known
      association; i.e., variants associated with key pro-social behaviours and mental
      disorders in humans. CONCLUSIONS: Only for one SNP on the OXTR gene (rs59190448)
      was a sign of positive directional selection detected with all three methods of
      selection detection. For rs59190448, however, only one phenotypical association
      is known, but rs59190448 is in high LD' (>0.8), with variants associated with
      important pro-social behaviours and mental disorders in humans. We also detected
      various signatures of balancing selection on both neuroreceptor genes.

PMID- 25968602
TI  - Miscellaneous additives can enhance plant uptake and affect geochemical fractions
      of copper in a heavily polluted riparian grassland soil.
AB  - The problem of copper (Cu) pollution in riverine ecosystems is world-wide and has
      significant environmental, eco-toxicological, and agricultural relevance. We
      assessed the suitability and effectiveness of application rate of 1% of activated
      charcoal, bentonite, biochar, cement kiln dust, chitosan, coal fly ash,
      limestone, nano-hydroxyapatite, organo-clay, sugar beet factory lime, and zeolite
      as soil amendments together with rapeseed as bioenergy crop as a possible
      remediation option for a heavily Cu polluted floodplain soil (total
      Cu=3041.9mgkg(-1)) that has a very high proportion of sorbed/carbonate fraction
      (484.6mgkg(-1)) and potential mobile fraction of Cu (1611.9mgkg(-1)). Application
      changed distribution of Cu among geochemical fractions: alkaline materials lead
      to increased carbonate bounded fraction and the acid rhizosphere zone might cause
      release of this Cu. Thus, mobilization of Cu and uptake of Cu by rapeseed were
      increased compared to the control (except for organo-clay) under the prevailing
      conditions. 

PMID- 25968603
TI  - Screening for bipolar disorder during pregnancy.
AB  - Bipolar disorder is a high-risk condition during pregnancy. In women receiving
      prenatal care, this study addresses the proportion screening positive for bipolar
      disorder with or without also screening positive for depression. This is a pilot
      study using chart abstraction of Edinburgh Postnatal Depression Scale (EPDS) and
      Mood Disorder Questionnaire (MDQ) scores from patients' initial prenatal visits.
      Among 342 participants, 289 (87.1 %) completed the EPDS, 277 (81.0 %) completed
      the MDQ, and 274 (80.1 %) completed both. Among EPDS screens, 49 (16.4 %) were
      positive. Among MDQ screens, 14 (5.1 %) were positive. Nine (21.4 %) of the 42
      participants with a positive EPDS also had a positive MDQ. Of the 14 patients
      with a positive MDQ, five (35.7 %) had a negative EPDS. The prevalence of
      positive screens for bipolar disorder in an obstetric population is similar to
      gestational diabetes and hypertension, which are screened for routinely. Without
      screening for bipolar disorder, there is a high risk of misclassifying bipolar
      depression as unipolar depression. If only women with current depressive symptoms
      are screened for bipolar disorder, approximately one third of bipolar disorder
      cases would be missed. If replicated, these findings support simultaneous
      screening for both depression and bipolar disorder during pregnancy. 

PMID- 25968604
TI  - Segregation of S292F TPO gene mutation in three large Tunisian families with
      thyroid dyshormonogenesis: evidence of a founder effect.
AB  - We aimed to identify causal mutation(s) in 13 patients with thyroid
      dyshormonogenesis (TD) from three consanguineous Tunisian families. A 12-year
      clinical follow-up showed phenotypic variability ranging from the presence to the
      absence of goiter, sensorineural deafness, and mental retardation. Genetic
      analysis using microsatellite markers within two candidate genes (TPO and PDS)
      gave evidence of linkage with the TPO gene. Sequencing of its 17 exons and their
      flanking intron-exon junctions revealed the previously described c.875C>T
      (p.S292F) mutation in homozygous state. No additional mutations were found in
      either a 900 bp of the TPO gene promoter or PDS gene. In silico analysis showed
      that p.S292F mutation might reduce the catalytic cavity of the TPO which would
      restrict access of a potential substrate to the catalytic pocket. Using 4SNPs and
      one microsatellite marker in the TPO gene, an associated haplotype: G-C-G-G-214
      was found, giving evidence of a founder mutation. CONCLUSION: This is the first
      description of a TD causing mutation in Tunisia and thus may help to develop a
      genetic screening protocol for congenital hypothyroidism in the studied region.
      Although structural modeling suggested a pathogenic effect of this mutation,
      functional studies are needed. Additional causing and/or modifier genes, together
      with late diagnosis could explain the clinical variability observed in our
      patients.

PMID- 25968606
TI  - Windows of achievement for development milestones of Sri Lankan infants and
      toddlers: estimation through statistical modelling.
AB  - BACKGROUND: The normative age ranges during which cohorts of children achieve
      milestones are called windows of achievement. The patterns of these windows of
      achievement are known to be both genetically and environmentally dependent. This
      study aimed to determine the windows of achievement for motor, social emotional,
      language and cognitive development milestones for infants and toddlers in Sri
      Lanka. METHODS: A set of 293 milestones identified through a literature review
      were subjected to content validation using parent and expert reviews, which
      resulted in the selection of a revised set of 277 milestones. Thereafter, a
      sample of 1036 children from 2 months to 30 months was examined to see whether or
      not they had attained the selected milestones. Percentile ages of attaining
      milestone were determined using a rearranged closed form equation related to the
      logistic regression. The parameters required for calculations were derived
      through the logistic regression of milestone achievement statuses against ages of
      children. These percentile ages were used to define the respective windows of
      achievement. RESULTS: A set of 178 robust indicators that represent motor, socio
      emotional, language and cognitive development skills and their windows of
      achievement relevant to 2 to 24 months of age were determined. Windows of
      achievement for six gross motor milestones determined in the study were shown to
      closely overlap a similar set of windows of achievement published by the World
      Health Organization indicating the validity of some findings. CONCLUSIONS: A
      methodology combining the content validation based on qualitative techniques and
      age validation based on regression modelling found to be effective for
      determining age percentiles for realizing milestones and determining respective
      windows of achievement.

PMID- 25968605
TI  - Directional cell movement through tissues is controlled by exosome secretion.
AB  - Directional cell movement through tissues is critical for multiple biological
      processes and requires maintenance of polarity in the face of complex
      environmental cues. Here we use intravital imaging to demonstrate that secretion
      of exosomes from late endosomes is required for directionally persistent and
      efficient in vivo movement of cancer cells. Inhibiting exosome secretion or
      biogenesis leads to defective tumour cell migration associated with increased
      formation of unstable protrusions and excessive directional switching. In vitro
      rescue experiments with purified exosomes and matrix coating identify adhesion
      assembly as a critical exosome function that promotes efficient cell motility.
      Live-cell imaging reveals that exosome secretion directly precedes and promotes
      adhesion assembly. Fibronectin is found to be a critical motility-promoting cargo
      whose sorting into exosomes depends on binding to integrins. We propose that
      autocrine secretion of exosomes powerfully promotes directionally persistent and
      effective cell motility by reinforcing otherwise transient polarization states
      and promoting adhesion assembly. 

PMID- 25968607
TI  - Common causes of vaginal infections and antibiotic susceptibility of aerobic
      bacterial isolates in women of reproductive age attending at Felegehiwot Referral
      Hospital, Ethiopia: a cross sectional study.
AB  - BACKGROUND: Bacterial vaginosis, candidal, trichomonal and Gonococcal vaginal
      infections are a major health problems associated with gynecologic complications
      and increase in replication, shedding and transmission of HIV and other STIs in
      women of reproductive age. The study aimed at determining the prevalence of
      common vaginal infections and antimicrobial susceptibility profiles of aerobic
      bacterial isolates in women of reproductive age, attending Felegehiwot referral
      Hospital. METHODS: A hospital based cross sectional study was conducted from May
      to November, 2013. Simple random sampling technique was used. Demographic
      variables were collected using a structured questionnaire. Clinical data were
      collected by physicians. Two vaginal swab specimens were collected from each
      participant. Wet mount and Gram staining were carried out to identify motile
      T.vaginalis, budding yeast and clue cells. All vaginal specimens were cultured
      for aerobic bacterial isolates using standard microbiology methods. Antimicrobial
      susceptibility was performed using disc diffusion technique as per the standard
      by Kirby-Bauer method. The results were analyzed using descriptive, chi-square
      and fisher's exact test as appropriate. RESULTS: A total of 409 women in
      reproductive age (15 - 49 years) participated in the study. The median age of the
      women was 28 years. Overall, 63 (15.4 %) of women had vaginal infections. The
      proportion of vaginal infection was higher in non-pregnant (17.3 %) than pregnant
      women (13.3 %) (P = 0.002). The most common identified vaginal infections were
      candidiasis (8.3 %) and bacterial vaginosis (2.8 %) followed by trichomoniasis
      (2.1 %). The isolation rate of N. gonorrhoeae and group B Streptococcus
      colonization was 4 (1 %) and 6 (1.2 %), respectively. Bacterial vaginosis was
      higher in non-pregnant (5.6 %) than pregnant women (0.5 %) (P = 0.002). Religion,
      age, living in rural area and having lower abdominal pain were significantly
      associated with bacterial vaginosis and candidiasis (P < 0.05). E.coli,
      Pseudomonas spp. and S.aureus were frequently isolated. Norfloxacin (75.6 %),
      ciprofloxacin (79.6 %) and gentamicin (77.6 %) revealed high level of sensitivity
      whereas high resistance rates were observed for amoxicillin (82.2 %),
      tetracycline (63.3 %) and cotrimoxazole (62.2 %). CONCLUSIONS: Bacterial
      vaginosis, candidiasis and trichomoniasis are a common problem in women of
      reproductive age. Therefore, screening of vaginal infections in women of
      reproductive age should be implemented. Moreover, ciprofloxacin, norfloxacin and
      gentamicin are the recommended drugs for empiric therapy and prophylaxis as
      needed.

PMID- 25968608
TI  - Impact of imiglucerase supply constraint on the therapeutic management and course
      of disease in French patients with Gaucher disease type 1.
AB  - BACKGROUND: In 2009, a worldwide supply constraint of imiglucerase led to
      treatment modifications or interruptions for patients with Gaucher disease (GD)
      type 1. In France, joint treatment recommendations were issued to protect the
      most vulnerable patients. This observational study evaluated the impact of
      imiglucerase treatment modifications on the clinical and biological course of GD.
      METHODS: Retrospective data on patients' characteristics, treatment, clinical and
      biological parameters from 01 June 2009 to 31 October 2010 were collected during
      a single visit. RESULTS: Ninety-nine GD1 patients, aged 7-84 years, were included
      (median age 47 years); 10 were children. Patients experienced a median of 4
      different treatment modifications. Median change from pre-supply constraint dose
      (92 U/kg/4-weeks) was -69, -51, -29 and -60 U/kg/4-weeks at 3, 6, 9 and 12 months
      after first modification, respectively, with imiglucerase discontinuation
      reported for 70%, 47%, 29% and 55% of patients at these timepoints. Replacement
      with another ERT was reported for 35 patients. Results show a statistically
      significant decrease in hemoglobin (-0.8 g/L/month) and platelets (
      5905.10(3)/mm(3)/month) and an increase in chitotriosidase (+537 nmol/mL/h/month)
      and angiotensin-converting enzyme (+4 IU/L/month) in the subgroup of 61 patients
      who discontinued treatment for at least 3 months; this magnitude of change was
      not seen in the subgroup (32 patients) treated with reduced imiglucerase for at
      least 3 consecutive months. GD-related events were spontaneously reported by the
      study investigators for 39% of the whole study population, including
      asthenia/fatigue (8%), bone infarction and bone pain (4% each), and hepatomegaly
      (3%). A Kaplan-Meier estimate of the probability for a patient to present a bone,
      hematological or visceral event during the constraint was 37% for patients who
      discontinued the treatment and 10% for patients treated with a reduced
      imiglucerase dose. CONCLUSION: The release of recommendations and individuals'
      close follow-up allowed satisfactory management of patients during the
      imiglucerase supply constraint in France. This study suggests that during this
      period, lowering the dose of imiglucerase had less impact on the outcomes of
      patients than interrupting treatment. However, general effects (such as fatigue,
      bone pain) reported in some patients, emphasize the importance of maintaining
      appropriate individualized dosing.

PMID- 25968609
TI  - The Use of Donation After Cardiac Death Allografts Does Not Increase Recurrence
      of Hepatocellular Carcinoma.
AB  - Hepatocellular carcinoma (HCC) recurrence in patients undergoing liver
      transplantation (LT) with donation after brain death (DBD) and donation after
      cardiac death (DCD) allografts has not previously been investigated. Rates and
      patterns of HCC recurrences were investigated in patients undergoing DBD (N =
      1633) and DCD (N = 243) LT between 2003 and 2012. LT for HCC was identified in
      397 patients (340 DBD and 57 DCD). No difference in tumor number (p = 0.26),
      tumor volume (p = 0.34) and serum alphafetoprotein (AFP) (p = 0.47) was seen
      between the groups. HCC recurrence was identified in 41 (12.1%) patients in the
      DBD group and 7 (12.3%) patients in the DCD group. There was no difference in
      recurrence-free survival (p = 0.29) or cumulative incidence of HCC recurrence (p
      = 0.91) between the groups. Liver allograft was the first site of recurrence in
      22 (65%) patients in the DBD group and two (37%) patients in the DCD group (p =
      0.39). LT for HCC with DBD and DCD allografts demonstrate no difference in the
      rate of HCC recurrence. Previously published differences in survival demonstrated
      between recipients with HCC receiving DBD and DCD allografts despite statistical
      adjustment can likely be explained by practice patterns not captured by variables
      contained in the SRTR database.

PMID- 25968610
TI  - Long-Term Normal Renal Function after Drastic Weight Reduction in Patients with
      Obesity-Related Glomerulopathy.
AB  - AIMS: No long-term studies of renal function evolution in morbidly obese (MO)
      patients after weight loss are available. The aim of our work was to ascertain
      the long-term influence of drastic weight reduction on renal function in MO
      patients with obesity-related glomerular lesions. METHODS: 92 MO patients with
      normal renal function and biopsy evidence of mild obesity-related glomerulopathy
      underwent bariatric surgery (BS) and subsequent drastic weight loss. A long-term
      prospective follow-up (mean duration: 76 +/- 42 months) was carried out. Basal
      renal biopsies and basal and long-term metabolic and renal function studies were
      performed in all cases. Linear mixed models were applied. RESULTS: Blood pressure
      dropped early after BS and remained stable thereafter. Creatinine clearance and
      BMI fell in the first 2 years, rose slightly after 5 years and then remained
      stable. Serum creatinine and albuminuria decreased throughout the follow-up
      period. Renal function and albuminuria evolution showed non-significant
      differences in relation to the number of glomerular lesions. CONCLUSIONS: Drastic
      weight loss in BS-treated MO patients with pre-surgical normal renal function and
      mild obesity-related glomerular lesions is associated with short- and long-term
      maintenance of normal renal function and improvement in both arterial
      hypertension and albuminuria.

PMID- 25968611
TI  - Determination of acid dissociation constants of warfarin and hydroxywarfarins by
      capillary electrophoresis.
AB  - In this work the acid dissociation constants--pKa of warfarin and its all
      important oxidative metabolites have been determined by capillary electrophoresis
      based methods. It has resulted in a complete description of two acid-base
      dissociation equilibria, yet not investigated experimentally for phase I
      metabolites of warfarin. The capillary electrophoresis (CE) method based on the
      relation between effective electrophoretic mobilities and pH has proven to be a
      suitable tool for pKa determination, while the spectrophotometric (CE-DAD) and
      the internal standard methods (IS-CE), have appeared to be promising alternative
      approaches. The CE-DAD approach based on the change in absorbance spectra between
      the acidic and basic forms is a combination between capillary electrophoresis and
      spectrophotometric titration, and yields very consistent values of pKa1 with CE.
      The IS-CE, in turn, enables an estimation of pKa1 and pKa2 from only two
      analytical runs, however, less accurate than CE and CE-DAD. The Debye-Huckel
      model has been confirmed experimentally as a good predictor of pKa values at
      various ionic strengths. Therefore, it has been used in determination of
      thermodynamic pKa1 and pKa2, referring to the zero ionic strength. The results
      are important from the analytical, pharmacological, and theoretical points of
      view.

PMID- 25968612
TI  - Influence of Dopant Loading on the Photo- and Electrochemical Properties of (N,
      O)-Co-doped Graphene.
AB  - A series of (N, O)-co-doped graphenes with different N and O loadings are
      prepared by the pyrolysis of natural chitosan. When the percentage of dopant
      increases, the conduction-band potential and charge-separation quantum yield
      increase, whereas the charge-separation lifetime decreases. 

PMID- 25968613
TI  - Comprehensive Analysis of Large Sets of Age-Related Physiological Indicators
      Reveals Rapid Aging around the Age of 55 Years.
AB  - BACKGROUND: While many studies show a correlation between chronological age and
      physiological indicators, the nature of this correlation is not fully understood.
      OBJECTIVE: To perform a comprehensive analysis of the correlation between
      chronological age and age-related physiological indicators. METHOD: Physiological
      aging scores were deduced using principal component analysis from a large dataset
      of 1,227 variables measured in a cohort of 4,796 human subjects, and the
      correlation between the physiological aging scores and chronological age was
      assessed. RESULTS: Physiological age does not progress linearly or exponentially
      with chronological age: a more rapid physiological change is observed around the
      age of 55 years, followed by a mild decline until around the age of 70 years.
      CONCLUSION: These findings provide evidence that the progression of physiological
      age is not linear with that of chronological age, and that periods of mild change
      in physiological age are separated by periods of more rapid aging.

PMID- 25968614
TI  - Cross-sectional sonographic assessment of the posterior interosseous nerve.
AB  - PURPOSE: Cross-sectional sonographic measurements are considered first-line
      confirmatory tests in diagnosing peripheral nerve entrapment syndromes. Our aim
      is to establish normal values of cross-sectional area of the posterior
      interosseous nerve (PIN) at the arcade of Frohse, the most common site of
      compression of this nerve. METHODS: The PIN was identified with ultrasound on 50
      healthy adults and 30 cadavers. Measurements of the cross-sectional area (CSA),
      antero-posterior (AP) and lateral (L) distances were taken immediately proximal
      and distal to the arcade of Frohse. RESULTS: The mean AP and L distances of the
      PIN proximal to the arcade of Frohse were 0.111 cm (0 +/- 0.021) and 0.266 cm (+/
      0.058), respectively, while the mean AP and L distances of the PIN distal to the
      arcade of Frohse were 0.085 cm (+/-0.019) and 0.343 cm (+/-0.057), respectively.
      P squared testing showed a statistically significant difference between the AP
      and lateral distances of the PIN when comparing proximal and distal to the arcade
      (p <= 0.001). However, the mean CSA of the PIN measured immediately proximal to
      the arcade of Frohse was 0.022 cm(2) (+/-0.005); immediately distal to the arcade
      of Frohse, it was 0.023 cm(2) (+/-0.004). t test showed no statistical difference
      between the two regions (p = 0.11). CONCLUSIONS: Our study has provided reference
      values for the PIN in healthy individuals at the arcade of Frohse. Although,
      there is a flattening of the nerve as it enters the supinator muscle, this should
      not be mistaken for nerve entrapment as the size of the nerve remains consistent.

PMID- 25968615
TI  - Ab initio modeling of Fe(II) adsorption and interfacial electron transfer at
      goethite (alpha-FeOOH) surfaces.
AB  - Goethite (alpha-FeOOH) surfaces represent one of the most ubiquitous redox-active
      interfaces in the environment, playing an important role in biogeochemical metal
      cycling and contaminant residence in the subsurface. Fe(II)-catalyzed
      recrystallization of goethite is a fundamental process in this context, but the
      proposed Fe(II)aq-Fe(III)goethite electron and iron atom exchange mechanism of
      recrystallization remains poorly understood at the atomic level. We examine the
      adsorption of aqueous Fe(II) and subsequent interfacial electron transfer (ET)
      between adsorbed Fe(II) and structural Fe(III) at the (110) and (021) goethite
      surfaces using density functional theory calculations including Hubbard U
      corrections (DFT + U) aided by ab initio molecular dynamics simulations. We
      investigate various surface sites for the adsorption of Fe(2+)(H2O)6 in different
      coordination environments. Calculated energies for adsorbed complexes at both
      surfaces favor monodentate complexes with reduced 4- and 5-fold coordination over
      higher-dentate structures and 6-fold coordination. The hydrolysis of H2O ligands
      is observed for some pre-ET adsorbed Fe(II) configurations. ET from the adsorbed
      Fe(II) into the goethite lattice is calculated to be energetically uphill always,
      but simultaneous proton transfer from H2O ligands of the adsorbed complexes to
      the surface oxygen species stabilizes post-ET states. We find that surface
      defects such as oxygen vacancies near the adsorption site also can stabilize post
      ET states, enabling the Fe(II)aq-Fe(III)goethite interfacial electron transfer
      reaction implied from experiments to proceed.

PMID- 25968616
TI  - Bis Expression in Patients with Surgically Resected Lung Cancer and its Clinical
      Significance.
AB  - BACKGROUND: Bis, also known as BAG3, has been identified as a Bcl-2-interacting
      protein that enhances cellular anti-apoptotic activity. It is involved in
      cellular differentiation, angiogenesis, migration, and invasion in various
      tumors. The purpose of this study was to investigate the Bis expression pattern,
      and the clinical significance thereof, in patients with resected lung cancer.
      METHODS: We studied 121 lung cancer patients who underwent curative surgical
      resection. Patient clinicopathological characteristics were reviewed
      retrospectively from medical records, including tumor recurrence and survival.
      The expression of Bis protein in lung cancer tissues was evaluated by
      immunohistochemical staining and was assessed using a four-tiered intensity score
      system (negative, weak, moderate, strong). Enhanced Bis expression at the
      periphery of a tumor facing the adjacent nontumor region was referred as
      "marginal activity." RESULTS: Although Bis expression was higher in squamous cell
      carcinoma than in adenocarcinoma, marginal activity was higher in adenocarcinoma
      than in squamous cell carcinoma. All of the small cell carcinomas and lung cancer
      with neuroendocrine differentiation examined were negative for Bis expression.
      Compared with stage I lung cancer, patients with stage II and IIIA lung cancer
      exhibited higher Bis protein levels in lung tissues. Recurrence and survival
      rates did not differ significantly according to Bis expression intensity score or
      marginal activity. CONCLUSIONS: Our study demonstrated that Bis expression
      differed according to the histological type and pathological stage of the lung
      cancer. Further studies are needed to assess its use as a biomarker and its role
      in the molecular pathogenesis of lung cancer.

PMID- 25968617
TI  - Two-Year Survival Analysis of 50 Consecutive Head and Neck Cancer Patients
      Treated with Transoral Robotic Surgery in a Single European Centre.
AB  - BACKGROUND: To date, this prospective cohort study is the largest of its kind
      from a single European academic tertiary care center to report 2-year survival
      outcomes for head and neck squamous cell carcinoma treated primarily with
      transoral robotic-assisted resection. PATIENTS AND METHODS: Fifty consecutive,
      appropriately staged patients were enrolled prospectively, and underwent
      transoral robotic surgery (TORS) between September 2011 and August 2013. Overall,
      24 patients had a T1 primary tumor, 23 had a T2 primary tumor, 2 had a T3 primary
      tumor, and 1 had a T4a primary tumor. Eighteen patients had overall stage I-II
      disease, and 32 patients had stage III-IV disease. Following transoral robotic
      resection of their primaries and appropriate neck dissection(s) as indicated,
      adjuvant treatment could be spared for 20 patients; another 5 patients refused
      the recommended adjuvant treatment. Seventeen patients received 60 Gy adjuvant
      radiotherapy and 8 patients underwent 66 Gy adjuvant chemoradiotherapy. RESULTS:
      At the time of the last follow-up visit (median 27 months), overall survival was
      94 %, with two disease-specific deaths and one unrelated death (heart attack).
      The 2-year disease-free and recurrence-free survival rates were 88 and 80 %,
      respectively; however, the local recurrence rate was only 10 % after 2 years.
      CONCLUSION: Using TORS as their primary modality, 40 % of patients did not need
      adjuvant treatment and showed similar survival rates to that of conventional
      surgery or primary chemoradiotherapy. In another 34 % of patients, adjuvant
      chemotherapy could be spared and adjuvant radiotherapy could be reduced by 10 Gy
      compared with primary chemoradiotherapy of 70 Gy. Further studies are warranted
      with respect to long-term survival.

PMID- 25968618
TI  - DNA Hypermethylation of SHISA3 in Colorectal Cancer: An Independent Predictor of
      Poor Prognosis.
AB  - BACKGROUND: Shisa3 is a novel tumor suppressor identified in lung cancer.
      However, its antitumor activity in other human cancers and the mechanism of gene
      inactivation remain unknown. METHODS: SHISA3 expression was measured by reverse
      transcription-PCR (RT-PCR) and quantitative RT-PCR (RT-qPCR). DNA methylation was
      determined by bisulfite sequencing and pyrosequencing. RESULTS: Down-regulation
      of SHISA3 expression was observed in all of 11 colorectal cancer (CRC) cell lines
      and was further confirmed in 34 (65.4 %) of 52 colorectal carcinomas by RT-qPCR.
      Four of six CRC cell lines could restore SHISA3 expression after treatment with 5
      aza-2'-deoxycytidine. Tumor-specific methylation of five CpG sites in the first
      intron of SHISA3 was identified by bisulfite sequencing, and their methylation
      levels were quantified in 127 pairs of primary CRC tissues by bisulfite
      pyrosequencing. The methylation levels of SHISA3 in tumors were noticeably higher
      than that in their matched normal mucosae. In addition, SHISA3 hypermethylation
      was significantly associated with an increased risk of disease recurrence in
      patients with stage II and III disease (P = 0.007) and was an independent
      predictor of poor overall survival [hazard ratio (HR) 2.9, 95 % confidence
      interval (CI) 1.5-5.8; P = 0.002] and disease-free survival (HR 4.0, 95 % CI 1.6
      10.2; P = 0.003) of CRC patients. CONCLUSIONS: SHISA3 gene is epigenetically
      inactivated in a substantial fraction of CRC, and its hypermethylation is of
      prognostic significance in predicting clinical outcome. The quantitative
      bisulfite pyrosequencing assay established could be a cost-effective tool for
      providing a potential biomarker of adverse prognosis in CRC.

PMID- 25968619
TI  - Circulating Tumor Cells After Neoadjuvant Chemotherapy in Stage I-III Triple
      Negative Breast Cancer.
AB  - BACKGROUND: Triple-negative breast cancer (TNBC) is characterized by a lack of
      estrogen and progesterone receptor expression and HER-2 gene amplification.
      Circulating tumor cells (CTCs) can be identified in 25 % of nonmetastatic breast
      cancer patients, and the identification of >=1 CTC predicts outcome. This study
      was designed to determine whether CTCs present after neoadjuvant chemotherapy
      (NACT) predicted worse outcome in nonmetastatic TNBC patients. METHODS: CTCs were
      assessed in 57 TNBC patients with nonmetastatic TNBC after the completion of
      NACT. CTCs (per 7.5 ml blood) were identified using the Cell Search((r)) System
      (Janssen). Log-rank test and Cox regression analysis were applied to establish
      the association of CTCs with relapse-free (RFS) and overall survival (OS).
      RESULTS: Median follow-up was 30 months, and mean age was 53 years. Fifty-four
      patients (95 %) had >2-cm tumors, 42 (84 %) were nuclear grade 3, and 42 (74 %)
      had positive axillary lymph nodes. One or more CTC was identified in 30 % of
      patients. CTC presence was not associated with primary tumor size, high grade, or
      lymph node positivity. Multivariate analysis demonstrated that detection of >=1
      CTC predicted decreased RFS (log-rank P = 0.03, HR 5.25, 95 % CI 1.34-20.56) and
      OS (log-rank P = 0.03, HR 7.04, 95 % CI 1.26-39.35). CONCLUSIONS: One or more
      CTCs present after NACT predicted relapse and survival in nonmetastatic TNBC
      patients. This information would be helpful in future clinical trial design of
      adjuvant treatments for TNBC patients who are at risk for relapse after
      completing NACT.

PMID- 25968621
TI  - Single-Institution Multidisciplinary Management of Locoregional Oligo-Recurrent
      Pelvic Malignancies: Long-Term Outcome Analysis.
AB  - PURPOSE: The aim of this study was to analyze long-term outcomes and prognostic
      factors associated with survival in patients with locoregional oligo-recurrent
      (LROR) pelvic malignancies treated in a multimodal protocol. METHODS: Patients
      with an histologic diagnosis of LROR pelvic cancer (rectal 50 %, gynecological 50
      %) with absence of distant metastases, undergoing surgery with radical intent and
      intraoperative radiotherapy (median dose 12.5 Gy) were considered eligible for
      participation in this study. Additionally, 48 % received external beam
      radiotherapy (EBRT) (median dose 50 Gy). RESULTS: From 1995 to 2012, a total of
      143 patients from a single institution were analyzed. With a median follow-up
      time of 48 months (range 2-189), 5-year locoregional control (LRC), disease-free
      survival (DFS), and overall survival (OS) were 53, 44, and 46 %, respectively. On
      multivariate analysis, no EBRT treatment to the locoregional (p <= 0.001), R1
      margin status (p = 0.03), time interval from primary tumor diagnosis to LROR <24
      months (p = 0.05), and fragmentation in the resected specimen (p = 0.004)
      retained significance in relation to LRC. On multivariate analysis we found that
      only R1 margin status (p = 0.003), primary tumor diagnosis to LROR <24 months (p
      = 0.02), and high histological grade (p = 0.02) were significantly associated
      with OS. CONCLUSIONS: From this analysis emerges the fact that EBRT influences
      local control but, given the high risk of distant metastases, DFS remains modest.
      Margin status, tumor fragmentation, no EBRT to the LR, and time interval from
      primary tumor diagnosis to LROR are the dominant factors for subsequent
      locoregional recurrence (LRR). Accordingly, future prospective studies might be
      designed which adapt treatment according to the predicted risk of subsequent LRR.

PMID- 25968620
TI  - Sentinel Lymph Node Mapping of Liver.
AB  - BACKGROUND: Although the sentinel lymph node (SLN) hypothesis has been applied to
      many tissues and organs, liver has remained unstudied. Currently, it is unclear
      whether hepatic SLNs even exist. If so, they could alter the management of
      intrahepatic cholangiocarcinoma and other hepatic malignancies by minimizing the
      extent of surgery while still providing precise nodal staging. This study
      investigated whether invisible yet tissue-penetrating near-infrared (NIR)
      fluorescent light can provide simultaneous identification of both the SLN and all
      other regional lymph nodes (RLNs) in the liver. METHODS: In 25 Yorkshire pigs,
      this study determined whether SLNs exist in liver and compared the effectiveness
      of two clinically available NIR fluorophores [methylene blue and indocyanine
      green (ICG)], and two novel NIR fluorophores previously described by our group
      (ESNF14 and ZW800-3C) for SLN and RLN mapping. RESULTS: In this study, ESNF14
      showed the highest signal-to-background ratio and the longest retention time in
      SLNs without leakage to second-tier lymph nodes. The findings showed that ICG had
      apparent leakage to second-tier nodes, and ZW800-3C had poor migration after
      intraparenchymal injection. However, when injected intravenously, ZW800-3C was
      able to highlight all RLNs in liver during a 4- to 6-h period. Simultaneous dual
      channel imaging of SLN (ESNF14) and RLN (ZW800-3C) permitted unambiguous
      identification and image-guided resection of SLNs and RLNs in liver. CONCLUSION:
      The NIR imaging technology enables real-time intraoperative identification of
      SLNs and RLNs in the liver of swine. If these results are confirmed in patients,
      new strategies for the surgical management of intrahepatic malignancies should be
      possible.

PMID- 25968622
TI  - Long-Term Outcome of Bilateral Laparoscopic Adrenalectomy Measured by Disease
      Specific Questionnaire in a Unique Group of Patients with Cushing's Syndrome.
AB  - BACKGROUND: Laparoscopic bilateral adrenalectomy (LBA) is recommended for
      patients with bilateral adrenal disease and occult or unresectable ectopic
      Cushing's syndrome (CS). There are limited data on long-term outcomes after LBA,
      partly due to the lack of disease-specific tools for the measurement of impact on
      patients' health and quality of life. METHODS: We used a disease-specific
      questionnaire covering all major clinicopathologic characteristics of CS. We
      compared the outcome from LBA to a control group of 60 patients who had
      thyroidectomy (matched for age, gender, and time of surgery, 2:1 control-to-CS).
      RESULTS: Twenty-eight patients (20 women and 8 men) underwent LBA for CS. Of
      them, 24 patients (86 %) provided responses to our questionnaire. Ninety-two
      percent of patients' responses indicated a significant improvement of general
      Cushing's physical features with complete resolution reported in 59 % of
      responses. Significant improvement of associated biochemical abnormalities and
      comorbidities was reported in 83 % of patients' responses including complete
      reversal in 58 %. Significant improvement in emotional-behavioral symptoms was
      reported in 84 % of patients' responses with complete recovery in 53 %. All
      patients expressed satisfaction with LBA and significant improvement in their
      general health and self-reported quality of life. All of the improvements after
      LBA were statistically significant compared with the control group. CONCLUSIONS:
      Our disease-specific questionnaire enables a clearer understanding of the
      association between the clinical, metabolic, and emotional-behavioral features of
      CS, its treatment with LBA, and long-term impact on patient-reported quality of
      life. This disease-specific questionnaire may be useful for future studies in
      patients with CS.

PMID- 25968624
TI  - Phytantriol Based "Stealth" Lyotropic Liquid Crystalline Nanoparticles for
      Improved Antitumor Efficacy and Reduced Toxicity of Docetaxel.
AB  - PURPOSE: The present work focuses on design and development of surface
      functionalized LCNPs for improving tumor delivery of DTX. METHODS: Phytantriol
      based "stealth" LCNPs were prepared using hydrotrope method and optimized. The
      potential of developed formulation was further assessed using cell culture
      experiments, in vivo pharmacokinetics, in vivo pharmacodynamics and toxicity
      studies. RESULTS: A biphasic drug release pattern was observed with sustained
      release of drug till 72 h. In vitro cell culture experiments revealed efficient
      internalization within MCF-7 cells with 25.80-fold decrease in IC50 value for PEG
      LCNPs as compared to free DTX. Mechanistic insights demonstrated preferential co
      localization of LCNPs in the vicinity of the nucleus. Furthermore, in vivo
      pharmacokinetic studies revealed 14.45-fold enhancement in circulation half-life
      of PEG-LCNPs as compared to marketed formulation Taxotere(r). In vivo efficacy
      studies PEG-LCNPs in DMBA induced breast cancer model revealed ~81% reduction in
      the tumor burden compared to Taxotere(r) which caused/achieve only 47% reduction
      or showed only 47% decrease. Furthermore, safety profile was noted for PEG-LCNPs
      as compared to Taxotere(r), measured as a function of hepato- and nephro
      toxicity. CONCLUSIONS: Surface functionalization of LCNPsis a viable approach for
      improving the therapeutic potential of DTX.

PMID- 25968625
TI  - Two macrocyclic polyamines as modulators of metal-mediated Abeta40 aggregation.
AB  - Dysfunctional interactions of amyloid-beta (Abeta) with Zn and Cu ions are proved
      to be related to the etiology of Alzheimer's disease (AD). Disruption of these
      metal-Abeta interactions using metal chelators holds considerable promise as a
      therapeutic strategy to combat this incurable disease. Herein, we report that two
      cyclam derivatives (L1 and L2) are capable of modulating Zn(2+)/Cu(2+)-mediated
      Abeta40 aggregation, reactive oxygen species (ROS) production, and neurotoxicity.
      These chelators were found to inhibit the metal-induced Abeta40 aggregation,
      dissociate metal-Abeta40 aggregates and restore the metal-induced beta-sheet
      structure of Abeta40 to its random coil conformation, as observed by BCA protein
      assay, thioflavin T fluorescence and circular dichroism spectroscopy. Moreover,
      preliminary investigation of SH-SY5Y cells indicates that L1 and L2 can diminish
      the neurotoxicity of metal-Abeta40 species, control metal-Abeta40-triggered ROS
      production and protect cells against apoptosis. These observations warrant the
      further investigations of L1 and L2 as potential anti-AD agents. 

PMID- 25968626
TI  - Epstein-Barr Virus-Positive Pyothorax-Associated Lymphoma Arising from a
      Posttraumatic Empyema.
AB  - Pyothorax-associated lymphoma (PAL) develops from a pyothorax caused by an
      artificial pneumothorax created during the treatment of pulmonary tuberculosis or
      tuberculous pleuritis. We report the first case of Epstein-Barr virus (EBV)
      positive PAL arising from a posttraumatic empyema. A 75-year-old woman with
      chronic posttraumatic empyema presented with a tumor, which was connected to the
      wall of a pyothorax in the right thoracic cavity. She had a history of trauma to
      the right chest, which had occurred at the age of 45 years and had caused the
      chronic posttraumatic empyema. Pathological features of the resected tumor were
      conclusive for a diagnosis of EBV-positive PAL. Although neither postoperative
      chemotherapy nor radiotherapy was performed, remission was maintained for 3 years
      until recurrence in the liver. Combination chemotherapy led to complete
      remission, and 9 years after the initial diagnosis of PAL, the patient is still
      alive. An intriguing finding is the phenotypic alteration during the disease
      course. Although the primary tumor was negative for CD20 and CD3, the recurrent
      tumor expressed both of these molecules. We discuss this case of PAL, which was
      not a complication of lung tuberculosis, and the aberrant chronological
      phenotypic change observed in the lymphoma cells, and compare it with a usual
      case of PAL. 

PMID- 25968628
TI  - Unique effect of an electric field on a new liquid crystalline lactic acid
      derivative.
AB  - A new chiral lactic acid derivative is presented, exhibiting a frustrated liquid
      crystalline phase, namely the orthogonal twist grain boundary TGBA phase in a
      broad temperature interval. A unique effect is observed that the applied electric
      field reversibly transforms the planar TGBA texture to the homeotropic one,
      homogeneously dark in crossed polarizers. The transformation is analogous to the
      Frederiks transition known in nematics, in which switching under electric field
      is driven by the positive dielectric anisotropy. A similar effect is established
      also in the SmA phase of the racemic mixture, where the field induced
      transformation is irreversible. A positive dielectric anisotropy in both the
      chiral compound and the racemic mixture is detected up to the frequency of about
      10 kHz, above this frequency the anisotropy is negative. The unusual behavior of
      the TGBA phase under the electric field can be explained by the specific packing
      of molecules within the smectic layers, resulting in a relatively high layer
      compressibility which lowers the energy of the structural defects and thus
      facilitates the structure transformation. The perfectly dark state of the studied
      compounds, induced by the electric field, either stable or reversible, is
      appealing for specific applications. The change of the sign of the dielectric
      anisotropy, known in nematics as the dual frequency effect, might be important
      for photonics such as adaptive or diffractive optics. 

PMID- 25968627
TI  - Infectious Myocarditis on FDG-PET Imaging Mimicking Sarcoidosis.
AB  - Cardiac positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG
      PET) is often used for the diagnosis of cardiac involvement in sarcoidosis. Areas
      of segmental perfusion defects coupled with FDG uptake are considered to
      represent active inflammation. However, these findings may be associated with
      other inflammatory myocardial diseases. We describe a case of tuberculous
      myocarditis with imaging findings mimicking those found in cardiac sarcoidosis. 

PMID- 25968633
TI  - Targeting L-type amino acid transporter 1 for anticancer therapy: clinical impact
      from diagnostics to therapeutics.
AB  - INTRODUCTION: L-type amino acid transporter 1 (LAT1) is one of the amino acid
      transporters. It is overexpressed in various types of cancer cells, while it is
      produced restrictedly in normal tissues. AREAS COVERED: We discuss its
      characteristics in cancer cells compared with normal cells. We also mention the
      current applications to target LAT1 for anticancer therapy focusing on prognostic
      biomarkers, radio-labeled tumor imaging reagents, amino acid-stapled prodrugs,
      LAT1-mediated enhanced transport of anticancer drugs and LAT1 inhibitors. EXPERT
      OPINION: LAT1 can be a versatile target to promisingly develop transporter-based
      drugs with enhanced drug delivery potential for anticancer therapy.

PMID- 25968634
TI  - Quality of life in cervical cancer treated with systematic nerve-sparing and
      modified radical hysterectomies.
AB  - The aim of this study was to compare the quality of life (QoL) between cervical
      cancer patients treated with systematic nerve-sparing radical hysterectomy
      (SNSRH) and modified radical hysterectomy (MRH). A total of 127 patients with
      early cervical cancer treated with radical hysterectomy (RH) were included in the
      study. The patients were divided into two groups: MRH group (n = ) and SNSRH
      group (n = ). The patients' QoL scores were assessed using the European
      Organization for Research and Treatment of Cancer Quality of Life Questionnaire
      Core 30 questionnaire (Chinese version). The overall QoL scores were no different
      between the SNSRH and MRH groups in preoperative period (P > 0.05). In
      postoperative period, the overall QoL score in SNSRH group was slightly lower
      than that in MRH group at different follow-up time, but there was no difference
      between two groups (P > 0.05). Patients with early cervical cancer subjected to
      SNSRH or MRH are satisfied with their overall QoL scores. QoL may be negatively
      impacted by the cancer itself, surgery and adjuvant therapy. 

PMID- 25968635
TI  - Ovarian vein thrombosis in pregnancy and the puerperium - A case series.

PMID- 25968636
TI  - Non-hormonal treatment of vulvo-vaginal atrophy-related symptoms in post
      menopausal women.
AB  - In post-menopausal period vulvo-vaginal atrophy (VVA)-related symptoms may
      seriously affect women's quality of life. Hormonal replacement therapy
      effectively relieves these symptoms but it is not always safe or accepted, and a
      non-hormonal treatment is often needed instead. Over a period of 12 weeks, we
      tested the effect of a twice-a-week vulvo-vaginal application of a hyaluronic
      acid, AC collagen, isoflavones and vitamins-based cream (Perilei Pausa) on 35
      women in post-menopausal period, reporting VVA-related symptoms. After 12 weeks
      of treatment with Perilei Pausa a significant improvement in vaginal dryness,
      vulvo-vaginal itching, dyspareunia (P < 0.001), dysuria (P = 0.02), nocturia (P =
      0.009) and pollakiuria (P = 0.005) was reported by the women. Colposcopical score
      assessing the intensity of atrophic colpitis, cervico-vaginal paleness and
      petechiae was also reduced (P = 0.037, P = 0.016 and P = 0.032, respectively). No
      significant difference in terms of maturation value of cervico-vaginal epithelium
      was observed. In conclusion, Perilei Pausa may represent an effective and safe
      alternative treatment of symptomatic VVA in post-menopausal women.

PMID- 25968637
TI  - Cellular immunotherapy as maintenance therapy prolongs the survival of the
      patients with small cell lung cancer.
AB  - BACKGROUND: Small cell lung cancer (SCLC) relapses rapidly after the initial
      response to chemotherapy and shows drug-resistance. This study was to investigate
      the efficacy and safety of cellular immunotherapy (CIT) with autologous natural
      killer (NK), gammadeltaT, and cytokine-induced killer (CIK) cells as maintenance
      therapy for SCLC patients. METHODS: A pilot prospective cohort study was
      conducted with SCLC patients who had responded to initial chemotherapy. Patients
      elected to receive either CIT as maintenance therapy (study group), or to be
      followed-up without further treatment (control group). Progression-free survival
      (PFS), overall survival (OS), and adverse effects were investigated. RESULTS: We
      recruited 58 patients (29 in each group). The patient characteristics of the 2
      groups were well balanced. PFS was not significantly different between the
      groups, but OS was significantly longer in the study group than the control (20
      vs. 11.5 months, P = 0.005; hazard ratio [HR], 0.434, 95 % confidence interval
      [CI], 0.236-0.797, P = 0.007). Among patients with limited-stage disease, there
      was no difference in PFS between the groups, but OS was longer in the study group
      compared to the control (26.5 vs. 11.8 months, P = 0.033; HR, 0.405, 95 % CI,
      0.169-0.972, P = 0.043). Among patients with extensive-stage disease, both PFS
      and OS were longer in the study group than the control (5 vs. 2.7 months, P =
      0.037; HR, 0.403, 95 % CI, 0.162-1.003, P = 0.051, and 14.5 vs. 9 months, P =
      0.038; HR, 0.403, 95 % CI, 0.165-0.987, P = 0.047, respectively). No significant
      adverse reactions occurred in patients undergoing CIT. CONCLUSIONS: CIT
      maintenance therapy in SCLC prolonged survival with only minimal side effects.
      Integrating CIT into current treatment may be a novel strategy for SCLC therapy,
      although further multi-center randomized studies are needed.

PMID- 25968638
TI  - Combined venomics, venom gland transcriptomics, bioactivities, and antivenomics
      of two Bothrops jararaca populations from geographic isolated regions within the
      Brazilian Atlantic rainforest.
AB  - Bothrops jararaca is a slender and semi-arboreal medically relevant pit viper
      species endemic to tropical and subtropical forests in southern Brazil, Paraguay,
      and northern Argentina (Misiones). Within its geographic range, it is often
      abundant and is an important cause of snakebite. Although no subspecies are
      currently recognized, geographic analyses have revealed the existence of two well
      supported B. jararaca clades that diverged during the Pliocene ~3.8Mya and
      currently display a southeastern (SE) and a southern (S) Atlantic rainforest
      (Mata Atlantica) distribution. The spectrum, geographic variability, and
      ontogenetic changes of the venom proteomes of snakes from these two B. jararaca
      phylogroups were investigated applying a combined venom gland transcriptomic and
      venomic analysis. Comparisons of the venom proteomes and transcriptomes of B.
      jararaca from the SE and S geographic regions revealed notable interpopulational
      variability that may be due to the different levels of population-specific
      transcriptional regulation, including, in the case of the southern population, a
      marked ontogenetic venom compositional change involving the upregulation of the
      myotoxic PLA2 homolog, bothropstoxin-I. This population-specific marker can be
      used to estimate the proportion of venom from the southern population present in
      the B. jararaca venom pool used for the Brazilian soro antibotropico (SAB)
      antivenom production. On the other hand, the southeastern population-specific D49
      PLA2 molecules, BinTX-I and BinTX-II, lend support to the notion that the
      mainland ancestor of Bothrops insularis was originated within the same population
      that gave rise to the current SE B. jararaca phylogroup, and that this insular
      species endemic to Queimada Grande Island (Brazil) expresses a pedomorphic venom
      phenotype. Mirroring their compositional divergence, the two geographic B.
      jararaca venom pools showed distinct bioactivity profiles. However, the SAB
      antivenom manufactured in Vital Brazil Institute neutralized the lethal effect of
      both venoms to a similar extent. In addition, immobilized SAB antivenom
      immunocaptured most of the venom components of the venoms of both B. jararaca
      populations, but did not show immunoreactivity against vasoactive peptides. The
      Costa Rican bothropic-crotalic-lachesic (BCL) antivenom showed the same lack of
      reactivity against vasoactive peptides but, in addition, was less efficient
      immunocapturing PI- and PIII-SVMPs from the SE venom, and bothropstoxin-I, a
      CRISP molecule, and a D49-PLA2 from the venom of the southern B. jararaca
      phylogroup. The remarkable paraspecificity exhibited by the Brazilian and the
      Costa Rican antivenoms indicates large immunoreactive epitope conservation across
      the natural history of Bothrops, a genus that has its roots in the middle
      Miocene. This article is part of a Special Issue entitled: Omics Evolutionary
      Ecolog. 

PMID- 25968641
TI  - Bacterial swarms recruit cargo bacteria to pave the way in toxic environments.
AB  - Swarming bacteria are challenged by the need to invade hostile environments.
      Swarms of the flagellated bacterium Paenibacillus vortex can collectively
      transport other microorganisms. Here we show that P. vortex can invade toxic
      environments by carrying antibiotic-degrading bacteria; this transport is
      mediated by a specialized, phenotypic subpopulation utilizing a process not
      dependent on cargo motility. Swarms of beta-lactam antibiotic (BLA)-sensitive P.
      vortex used beta-lactamase-producing, resistant, cargo bacteria to detoxify BLAs
      in their path. In the presence of BLAs, both transporter and cargo bacteria
      gained from this temporary cooperation; there was a positive correlation between
      BLA resistance and dispersal. P. vortex transported only the most beneficial
      antibiotic-resistant cargo (including environmental and clinical isolates) in a
      sustained way. P. vortex displayed a bet-hedging strategy that promoted the
      colonization of nontoxic niches by P. vortex alone; when detoxifying cargo
      bacteria were not needed, they were lost. This work has relevance for the
      dispersal of antibiotic-resistant microorganisms and for strategies for
      asymmetric cooperation with agricultural and medical implications. IMPORTANCE:
      Antibiotic resistance is a major health threat. We show a novel mechanism for the
      local spread of antibiotic resistance. This involves interactions between
      different bacteria: one species provides an enzyme that detoxifies the antibiotic
      (a sessile cargo bacterium carrying a resistance gene), while the other
      (Paenibacillus vortex) moves itself and transports the cargo. P. vortex used a
      bet-hedging strategy, colonizing new environments alone when the cargo added no
      benefit, but cooperating when the cargo was needed. This work is of interest in
      an evolutionary context and sheds light on fundamental questions, such as how
      environmental antibiotic resistance may lead to clinical resistance and also
      microbial social organization, as well as the costs, benefits, and risks of
      dispersal in the environment.

PMID- 25968642
TI  - Clustered Regularly Interspaced Short Palindromic Repeat-Dependent, Biofilm
      Specific Death of Pseudomonas aeruginosa Mediated by Increased Expression of
      Phage-Related Genes.
AB  - The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR
      associated (CRISPR/Cas) system is an adaptive immune system present in many
      archaea and bacteria. CRISPR/Cas systems are incredibly diverse, and there is
      increasing evidence of CRISPR/Cas systems playing a role in cellular functions
      distinct from phage immunity. Previously, our laboratory reported one such
      alternate function in which the type 1-F CRISPR/Cas system of the opportunistic
      pathogen Pseudomonas aeruginosa strain UCBPP-PA14 (abbreviated as P. aeruginosa
      PA14) inhibits both biofilm formation and swarming motility when the bacterium is
      lysogenized by the bacteriophage DMS3. In this study, we demonstrated that the
      presence of just the DMS3 protospacer and the protospacer-adjacent motif (PAM) on
      the P. aeruginosa genome is necessary and sufficient for this CRISPR-dependent
      loss of these group behaviors, with no requirement of additional DMS3 sequences.
      We also demonstrated that the interaction of the CRISPR system with the DMS3
      protospacer induces expression of SOS-regulated phage-related genes, including
      the well-characterized pyocin operon, through the activity of the nuclease Cas3
      and subsequent RecA activation. Furthermore, our data suggest that expression of
      the phage-related genes results in bacterial cell death on a surface due to the
      inability of the CRISPR-engaged strain to downregulate phage-related gene
      expression, while these phage-related genes have minimal impact on growth and
      viability under planktonic conditions. Deletion of the phage-related genes
      restores biofilm formation and swarming motility while still maintaining a
      functional CRISPR/Cas system, demonstrating that the loss of these group
      behaviors is an indirect effect of CRISPR self-targeting. IMPORTANCE: The various
      CRISPR/Cas systems found in both archaea and bacteria are incredibly diverse, and
      advances in understanding the complex mechanisms of these varied systems has not
      only increased our knowledge of host-virus interplay but has also led to a major
      advancement in genetic engineering. Recently, increasing evidence suggested that
      bacteria can co-opt the CRISPR system for functions besides adaptive immunity to
      phage infection. This study examined one such alternative function, and this
      report describes the mechanism of type 1-F CRISPR-dependent loss of the biofilm
      and swarming in the medically relevant opportunistic pathogen Pseudomonas
      aeruginosa. Since both biofilm formation and swarming motility are important in
      the virulence of P. aeruginosa, a full understanding of how the CRISPR system can
      regulate such group behaviors is fundamental to developing new therapeutics.

PMID- 25968643
TI  - Novel mechanism for scavenging of hypochlorite involving a periplasmic methionine
      rich Peptide and methionine sulfoxide reductase.
AB  - Reactive chlorine species (RCS) defense mechanisms are important for bacterial
      fitness in diverse environments. In addition to the anthropogenic use of RCS in
      the form of bleach, these compounds are also produced naturally through
      photochemical reactions of natural organic matter and in vivo by the mammalian
      immune system in response to invading microorganisms. To gain insight into
      bacterial RCS defense mechanisms, we investigated Azospira suillum strain PS,
      which produces periplasmic RCS as an intermediate of perchlorate respiration. Our
      studies identified an RCS response involving an RCS stress-sensing sigma/anti
      sigma factor system (SigF/NrsF), a soluble hypochlorite-scavenging methionine
      rich periplasmic protein (MrpX), and a putative periplasmic methionine sulfoxide
      reductase (YedY1). We investigated the underlying mechanism by phenotypic
      characterization of appropriate gene deletions, chemogenomic profiling of
      barcoded transposon pools, transcriptome sequencing, and biochemical assessment
      of methionine oxidation. Our results demonstrated that SigF was specifically
      activated by RCS and initiated the transcription of a small regulon centering
      around yedY1 and mrpX. A yedY1 paralog (yedY2) was found to have a similar
      fitness to yedY1 despite not being regulated by SigF. Markerless deletions of
      yedY2 confirmed its synergy with the SigF regulon. MrpX was strongly induced and
      rapidly oxidized by RCS, especially hypochlorite. Our results suggest a mechanism
      involving hypochlorite scavenging by sacrificial oxidation of the MrpX in the
      periplasm. Reduced MrpX is regenerated by the YedY methionine sulfoxide reductase
      activity. The phylogenomic distribution of this system revealed conservation in
      several Proteobacteria of clinical importance, including uropathogenic
      Escherichia coli and Brucella spp., implying a putative role in immune response
      evasion in vivo. IMPORTANCE: Bacteria are often stressed in the environment by
      reactive chlorine species (RCS) of either anthropogenic or natural origin, but
      little is known of the defense mechanisms they have evolved. Using a
      microorganism that generates RCS internally as part of its respiratory process
      allowed us to uncover a novel defense mechanism based on RCS scavenging by
      reductive reaction with a sacrificial methionine-rich peptide and redox recycling
      through a methionine sulfoxide reductase. This system is conserved in a broad
      diversity of organisms, including some of clinical importance, invoking a
      possible important role in innate immune system evasion.

PMID- 25968644
TI  - Rapid quantification of mutant fitness in diverse bacteria by sequencing randomly
      bar-coded transposons.
AB  - Transposon mutagenesis with next-generation sequencing (TnSeq) is a powerful
      approach to annotate gene function in bacteria, but existing protocols for TnSeq
      require laborious preparation of every sample before sequencing. Thus, the
      existing protocols are not amenable to the throughput necessary to identify
      phenotypes and functions for the majority of genes in diverse bacteria. Here, we
      present a method, random bar code transposon-site sequencing (RB-TnSeq), which
      increases the throughput of mutant fitness profiling by incorporating random DNA
      bar codes into Tn5 and mariner transposons and by using bar code sequencing
      (BarSeq) to assay mutant fitness. RB-TnSeq can be used with any transposon, and
      TnSeq is performed once per organism instead of once per sample. Each BarSeq
      assay requires only a simple PCR, and 48 to 96 samples can be sequenced on one
      lane of an Illumina HiSeq system. We demonstrate the reproducibility and
      biological significance of RB-TnSeq with Escherichia coli, Phaeobacter inhibens,
      Pseudomonas stutzeri, Shewanella amazonensis, and Shewanella oneidensis. To
      demonstrate the increased throughput of RB-TnSeq, we performed 387 successful
      genome-wide mutant fitness assays representing 130 different bacterium-carbon
      source combinations and identified 5,196 genes with significant phenotypes across
      the five bacteria. In P. inhibens, we used our mutant fitness data to identify
      genes important for the utilization of diverse carbon substrates, including a
      putative d-mannose isomerase that is required for mannitol catabolism. RB-TnSeq
      will enable the cost-effective functional annotation of diverse bacteria using
      mutant fitness profiling. IMPORTANCE: A large challenge in microbiology is the
      functional assessment of the millions of uncharacterized genes identified by
      genome sequencing. Transposon mutagenesis coupled to next-generation sequencing
      (TnSeq) is a powerful approach to assign phenotypes and functions to genes.
      However, the current strategies for TnSeq are too laborious to be applied to
      hundreds of experimental conditions across multiple bacteria. Here, we describe
      an approach, random bar code transposon-site sequencing (RB-TnSeq), which greatly
      simplifies the measurement of gene fitness by using bar code sequencing (BarSeq)
      to monitor the abundance of mutants. We performed 387 genome-wide fitness assays
      across five bacteria and identified phenotypes for over 5,000 genes. RB-TnSeq can
      be applied to diverse bacteria and is a powerful tool to annotate uncharacterized
      genes using phenotype data.

PMID- 25968646
TI  - Identification of Quorum-Sensing Inhibitors Disrupting Signaling between Rgg and
      Short Hydrophobic Peptides in Streptococci.
AB  - Bacteria coordinate a variety of social behaviors, important for both
      environmental and pathogenic bacteria, through a process of intercellular
      chemical signaling known as quorum sensing (QS). As microbial resistance to
      antibiotics grows more common, a critical need has emerged to develop novel anti
      infective therapies, such as an ability to attenuate bacterial pathogens by means
      of QS interference. Rgg quorum-sensing pathways, widespread in the phylum
      Firmicutes, employ cytoplasmic pheromone receptors (Rgg transcription factors)
      that directly bind and elicit gene expression responses to imported peptide
      signals. In the human-restricted pathogen Streptococcus pyogenes, the Rgg2/Rgg3
      regulatory circuit controls biofilm development in response to the short
      hydrophobic peptides SHP2 and SHP3. Using Rgg-SHP as a model receptor-ligand
      target, we sought to identify chemical compounds that could specifically inhibit
      Rgg quorum-sensing circuits. Individual compounds from a diverse library of known
      drugs and drug-like molecules were screened for their ability to disrupt
      complexes of Rgg and FITC (fluorescein isothiocyanate)-conjugated SHP using a
      fluorescence polarization (FP) assay. The best hits were found to bind Rgg3 in
      vitro with submicromolar affinities, to specifically abolish transcription of
      Rgg2/3-controlled genes, and to prevent biofilm development in S. pyogenes
      without affecting bacterial growth. Furthermore, the top hit, cyclosporine A, as
      well as its nonimmunosuppressive analog, valspodar, inhibited Rgg-SHP pathways in
      multiple species of Streptococcus. The Rgg-FITC-peptide-based screen provides a
      platform to identify inhibitors specific for each Rgg type. Discovery of Rgg
      inhibitors constitutes a step toward the goal of manipulating bacterial behavior
      for purposes of improving health. IMPORTANCE: The global emergence of antibiotic
      resistant bacterial infections necessitates discovery not only of new
      antimicrobials but also of novel drug targets. Since antibiotics restrict
      microbial growth, strong selective pressures to develop resistance emerge quickly
      in bacteria. A new strategy to fight microbial infections has been proposed,
      namely, development of therapies that decrease pathogenicity of invading
      organisms while not directly inhibiting their growth, thus decreasing selective
      pressure to establish resistance. One possible means to this goal is to interfere
      with chemical communication networks used by bacteria to coordinate group
      behaviors, which can include the synchronized expression of genes that lead to
      disease. In this study, we identified chemical compounds that disrupt
      communication pathways regulated by Rgg proteins in species of Streptococcus.
      Treatment of cultures of S. pyogenes with the inhibitors diminished the
      development of biofilms, demonstrating an ability to control bacterial behavior
      with chemicals that do not inhibit growth.

PMID- 25968645
TI  - Natural bacterial communities serve as quantitative geochemical biosensors.
AB  - Biological sensors can be engineered to measure a wide range of environmental
      conditions. Here we show that statistical analysis of DNA from natural microbial
      communities can be used to accurately identify environmental contaminants,
      including uranium and nitrate at a nuclear waste site. In addition to
      contamination, sequence data from the 16S rRNA gene alone can quantitatively
      predict a rich catalogue of 26 geochemical features collected from 93 wells with
      highly differing geochemistry characteristics. We extend this approach to
      identify sites contaminated with hydrocarbons from the Deepwater Horizon oil
      spill, finding that altered bacterial communities encode a memory of prior
      contamination, even after the contaminants themselves have been fully degraded.
      We show that the bacterial strains that are most useful for detecting oil and
      uranium are known to interact with these substrates, indicating that this
      statistical approach uncovers ecologically meaningful interactions consistent
      with previous experimental observations. Future efforts should focus on
      evaluating the geographical generalizability of these associations. Taken as a
      whole, these results indicate that ubiquitous, natural bacterial communities can
      be used as in situ environmental sensors that respond to and capture
      perturbations caused by human impacts. These in situ biosensors rely on
      environmental selection rather than directed engineering, and so this approach
      could be rapidly deployed and scaled as sequencing technology continues to become
      faster, simpler, and less expensive. IMPORTANCE: Here we show that DNA from
      natural bacterial communities can be used as a quantitative biosensor to
      accurately distinguish unpolluted sites from those contaminated with uranium,
      nitrate, or oil. These results indicate that bacterial communities can be used as
      environmental sensors that respond to and capture perturbations caused by human
      impacts.

PMID- 25968647
TI  - Alginate Polymerization and Modification Are Linked in Pseudomonas aeruginosa.
AB  - The molecular mechanisms of alginate polymerization/modification/secretion by a
      proposed envelope-spanning multiprotein complex are unknown. Here, bacterial two
      hybrid assays and pulldown experiments showed that the catalytic subunit Alg8
      directly interacts with the proposed copolymerase Alg44 while embedded in the
      cytoplasmic membrane. Alg44 additionally interacts with the lipoprotein AlgK
      bridging the periplasmic space. Site-specific mutagenesis of Alg44 showed that
      protein-protein interactions and stability were independent of conserved amino
      acid residues R17 and R21, which are involved in c-di-GMP binding, the N-terminal
      PilZ domain, and the C-terminal 26 amino acids. Site-specific mutagenesis was
      employed to investigate the c-di-GMP-mediated activation of alginate
      polymerization by the PilZAlg44 domain and Alg8. Activation was found to be
      different from the proposed activation mechanism for cellulose synthesis. The
      interactive role of Alg8, Alg44, AlgG (epimerase), and AlgX (acetyltransferase)
      on alginate polymerization and modification was studied by using site-specific
      deletion mutants, inactive variants, and overproduction of subunits. The
      compositions, molecular masses, and material properties of resulting novel
      alginates were analyzed. The molecular mass was reduced by epimerization, while
      it was increased by acetylation. Interestingly, when overproduced, Alg44, AlgG,
      and the nonepimerizing variant AlgG(D324A) increased the degree of acetylation,
      while epimerization was enhanced by AlgX and its nonacetylating variant
      AlgX(S269A). Biofilm architecture analysis showed that acetyl groups promoted
      cell aggregation while nonacetylated polymannuronate alginate promoted stigmergy.
      Overall, this study sheds new light on the arrangement of the multiprotein
      complex involved in alginate production. Furthermore, the activation mechanism
      and the interplay between polymerization and modification of alginate were
      elucidated. IMPORTANCE: This study provides new insights into the molecular
      mechanisms of the synthesis of the unique polysaccharide, alginate, which not
      only is an important virulence factor of the opportunistic human pathogen
      Pseudomonas aeruginosa but also has, due to its material properties, many
      applications in medicine and industry. Unraveling the assembly and composition of
      the alginate-synthesizing and envelope-spanning multiprotein complex will be of
      tremendous significance for the scientific community. We identified a protein
      protein interaction network inside the multiprotein complex and studied its
      relevance with respect to alginate polymerization/modification as well as the c
      di-GMP-mediated activation mechanism. A relationship between alginate
      polymerization and modification was shown. Due to the role of alginate in
      pathogenesis as well as its unique material properties harnessed in numerous
      applications, results obtained in this study will aid the design and development
      of inhibitory drugs as well as the commercial bacterial production of tailor-made
      alginates.

PMID- 25968648
TI  - Dengue Virus NS Proteins Inhibit RIG-I/MAVS Signaling by Blocking TBK1/IRF3
      Phosphorylation: Dengue Virus Serotype 1 NS4A Is a Unique Interferon-Regulating
      Virulence Determinant.
AB  - Dengue virus (DENV) replication is inhibited by the prior addition of type I
      interferon or by RIG-I agonists that elicit RIG-I/MAVS/TBK1/IRF3-dependent
      protective responses. DENV infection of primary human endothelial cells (ECs)
      results in a rapid increase in viral titer, which suggests that DENV inhibits
      replication-restrictive RIG-I/interferon beta (IFN-beta) induction pathways
      within ECs. Our findings demonstrate that DENV serotype 4 (DENV4) nonstructural
      (NS) proteins NS2A and NS4B inhibited RIG-I-, MDA5-, MAVS-, and TBK1/IKKepsilon
      directed IFN-beta transcription (>80%) but failed to inhibit IFN-beta induction
      directed by STING or constitutively active IRF3-5D. Expression of NS2A and NS4B
      dose dependently inhibited the phosphorylation of TBK1 and IRF3, which suggests
      that they function at the level of TBK1 complex activation. NS2A and NS4B from
      DENV1/2/4, as well as the West Nile virus NS4B protein, commonly inhibited TBK1
      phosphorylation and IFN-beta induction. A comparative analysis of NS4A proteins
      across DENVs demonstrated that DENV1, but not DENV2 or DENV4, NS4A proteins
      uniquely inhibited TBK1. These findings indicate that DENVs contain conserved
      (NS2A/NS4B) and DENV1-specific (NS4A) mechanisms for inhibiting RIG-I/TBK1
      directed IFN responses. Collectively, our results define DENV NS proteins that
      restrict IRF3 and IFN responses and thereby facilitate DENV replication and
      virulence. Unique DENV1-specific NS4A regulation of IFN induction has the
      potential to be a virulence determinant that contributes to the increased
      severity of DENV1 infections and the immunodominance of DENV1 responses during
      tetravalent DENV1-4 vaccination. IMPORTANCE: Our findings demonstrate that NS2A
      and NS4B proteins from dengue virus serotypes 1, 2, and 4 are inhibitors of RIG
      I/MDA5-directed interferon beta (IFN-beta) induction and that they accomplish
      this by blocking TBK1 activation. We determined that IFN inhibition is
      functionally conserved across NS4B proteins from West Nile virus and DENV1, -2,
      and -4 viruses. In contrast, DENV1 uniquely encodes an extra IFN regulating
      protein, NS4A, that inhibits TBK1-directed IFN induction. DENV1 is associated
      with an increase in severe patient disease, and added IFN regulation by the DENV1
      NS4A protein may contribute to increased DENV1 replication, immunodominance, and
      virulence. The regulation of IFN induction by nonstructural (NS) proteins
      suggests their potential roles in enhancing viral replication and spread and as
      potential protein targets for viral attenuation. DENV1-specific IFN regulation
      needs to be considered in vaccine strategies where enhanced DENV1 replication may
      interfere with DENV2-4 seroconversion within coadministered tetravalent DENV1-4
      vaccines.

PMID- 25968649
TI  - Mutations in the Borrelia burgdorferi Flagellar Type III Secretion System Genes
      fliH and fliI Profoundly Affect Spirochete Flagellar Assembly, Morphology,
      Motility, Structure, and Cell Division.
AB  - The Lyme disease spirochete Borrelia burgdorferi migrates to distant sites in the
      tick vectors and mammalian hosts through robust motility and chemotaxis
      activities. FliH and FliI are two cytoplasmic proteins that play important roles
      in the type III secretion system (T3SS)-mediated export and assembly of flagellar
      structural proteins. However, detailed analyses of the roles of FliH and FliI in
      B. burgdorferi have not been reported. In this study, fliH and fliI transposon
      mutants were utilized to dissect the mechanism of the Borrelia type III secretion
      system. The fliH and fliI mutants exhibited rod-shaped or string-like morphology,
      greatly reduced motility, division defects (resulting in elongated organisms with
      incomplete division points), and noninfectivity in mice by needle inoculation.
      Mutants in fliH and fliI were incapable of translational motion in 1%
      methylcellulose or soft agar. Inactivation of either fliH or fliI resulted in the
      loss of the FliH-FliI complex from otherwise intact flagellar motors, as
      determined by cryo-electron tomography (cryo-ET). Flagellar assemblies were still
      present in the mutant cells, albeit in lower numbers than in wild-type cells and
      with truncated flagella. Genetic complementation of fliH and fliI mutants in
      trans restored their wild-type morphology, motility, and flagellar motor
      structure; however, full-length flagella and infectivity were not recovered in
      these complemented mutants. Based on these results, disruption of either fliH or
      fliI in B. burgdorferi results in a severe defect in flagellar structure and
      function and cell division but does not completely block the export and assembly
      of flagellar hook and filament proteins. IMPORTANCE: Many bacteria are able to
      rapidly transport themselves through their surroundings using specialized
      organelles called flagella. In spiral-shaped organisms called spirochetes,
      flagella act like inboard motors and give the bacteria the ability to bore their
      way through dense materials (such as human tissue) in a corkscrew manner. In this
      article, we studied how two proteins, called FliH and FliI, are important for the
      production of full-length flagella in the Lyme disease spirochete Borrelia
      burgdorferi. Mutants with defective production of FliH and FliI have reduced
      flagellar length and motility; this deficiency in turn affects many aspects of B.
      burgdorferi's biology, including the ability to undergo cell division and cause
      disease in mammals. Using a microscopic computed tomography (CT) scan approach
      called cryo-electron tomography, the structure that contains FliH and FliI was
      defined in the context of the flagellar motor, providing clues regarding how this
      amazing nanomachine is assembled and functions.

PMID- 25968650
TI  - [Help-seeking behavior and pathways to care for patients with obsessive
      compulsive disorders].
AB  - BACKGROUND: Obsessive-compulsive disorder (OCD) is a chronic and debilitating
      disorder that is relatively common and is associated with a wide range of
      functional impairments. This is partly associated with delayed help-seeking
      behavior of OCD patients, which shows a lag of up to 10 years after onset of the
      obsessive-compulsive symptoms to the first attempt at seeking professional
      treatment. The reasons for the delay in initial help-seeking behavior by OCD
      patients are manifold but still not clear. Early detection and early treatment
      might, however, have beneficial effects on the treatment-seeking behavior. AIM:
      The aim of the study was to examine the help-seeking behavior and the pathways to
      care of patients with OCD using a modified version of the structured pathways to
      care questionnaire initially designed for research into schizophrenia. RESULTS:
      For the 40 outpatients with OCD who completed the interview retrospectively, the
      latent period between symptom onset and first seeking professional contact was on
      average 6.5 years, while the median delay to a third attempt at seeking treatment
      was nearly 15 years. Although the majority of participants consulted a
      professional neurological and psychotherapeutic practice even at the first
      attempt and 90% complained of specific OCD symptoms, only 20% received the
      standard treatment consisting of cognitive behavioral therapy and medication with
      a selective serotonin reuptake inhibitor (SSRI). The most common reason for
      delaying seeking treatment was that the patient was not convinced of having a
      mental illness such as OCD and of the necessity for treatment. Even so,
      approximately 40% of the participants reported fear of stigmatization and
      discrimination as a major reason for the delay in the first attempt at seeking
      help. CONCLUSION: Psychoeducation and broad utilization of evidence-based
      treatment still appears necessary and can contribute to improvement in the help
      seeking behavior of OCD patients.

PMID- 25968651
TI  - [Research on humans suffering from dementia].
AB  - The urgent necessity for dementia research is justified by the prevalence and
      increase in dementia associated with the demographic changes, for which no causal
      treatment is available; however, during the progressive course dementia destroys
      the capacity for self-determination of persons affected and thereby an essential
      prerequisite for participation in research, i.e. a valid consent to a research
      intervention. Accordingly, not only sufficient information about all issues which
      are relevant for decision making by potential participants but also a flawless
      assessment of the capacity to consent are important; however, currently this is
      not satisfactorily possible. This article attempts to answer questions associated
      with these problems, such as how consent can be established, including that of a
      surrogate for consent of potential research participants by whom consent is no
      longer possible. In a second section the benefit-risk evaluation, which is also
      underdeveloped, will be dealt with using two concrete research examples, a
      diagnostic and a therapeutic research intervention for patients with dementia. 

PMID- 25968652
TI  - Are Elevated Serum Triglycerides Really a Risk Factor for Coronary Artery
      Disease?

PMID- 25968653
TI  - Dynamic changes in myeloid derived suppressor cell subsets following renal
      transplant: A prospective study.
AB  - BACKGROUND: Myeloid-derived suppressor cells (MDSC) are powerful suppressors of
      immune responses. MDSC numbers are increased in some renal transplant recipients
      (RTR) and there is increasing interest in their potential role in promoting both
      transplant tolerance and transplant associated malignancy. However the factors
      influencing MDSC mobilisation are unknown, and the relative temporal changes in
      the granulocytic (G-MDSC) and monocytic (Mo-MDSC) subsets of MDSC have not been
      defined. METHODS: The circulating frequencies of MDSC and dendritic cells (DC)
      were analysed by multicolour flow cytometry in RTR (n = 8) prior to transplant
      and at regular intervals out to 1 year post-transplant. RESULTS: In RTRs, numbers
      of both G-MDSC and Mo-MDSC increased rapidly following transplant and peaked
      within 8 days, whilst DC numbers decreased. A second peak in G-MDSC numbers was
      observed in 7/8 patients within 3 months and 2 patients had a further 3rd peak in
      G-MDSC numbers which, in one patient, corresponded to a rejection event. Mo-MDSC
      numbers underwent less fluctuation and a subsequent peak in numbers was observed
      in only 2/8 patients. Respective kidney donors (n = 5) underwent only small
      transient increases in MDSC following surgery. Overall, there was little
      correlation between increases in MDSC and the occurrence of detectable clinical
      events or treatment changes. CONCLUSIONS: In RTRs, MDSC numbers increase rapidly
      and peak following commencement of immunosuppression, but then fluctuate in
      response to as yet undefined stimuli. Further studies are required to identify
      the factors modulating MDSC mobilisation.

PMID- 25968654
TI  - Adverse Events During Immunotherapy Against Grass Pollen-Induced Allergic
      Rhinitis - Differences Between Subcutaneous and Sublingual Treatment.
AB  - Allergic rhinitis (AR) triggered by grass pollen is a common disease, affecting
      millions of people worldwide. Treatment consists of symptom-alleviating drugs,
      such as topical corticosteroids or antihistamines. Another option is potentially
      curative immunotherapy, currently available as sublingual and subcutaneous
      treatment. We investigated the potential differences in the prevalence and
      severity of adverse events related to subcutaneous and sublingual immunotherapy
      (SLIT) against grass pollen-induced AR. A thorough literature search was
      performed with PubMed and EMBASE. The findings were compared with the available
      summaries of product characteristics (SPC) and with commercial pharmacology
      databases (Micromedex). The majority of available safety data originate from
      registered products of standardized allergens. A surprisingly large percentage of
      drugs, especially those used in the United States, have no systematically
      collected safety data. No sufficiently powered randomized trials comparing
      sublingual and subcutaneous immunotherapy (SCIT) were available, but general
      safety assessments indicate that sublingual tablet treatment is safer than
      subcutaneous treatment. Not all commonly used immunotherapy drugs are officially
      registered, and not all have systematically collected safety data. This is
      especially true for older drugs used in the United States. In contrast, newer
      drugs that have undergone extensive clinical testing have better documentation,
      but unified collection of safety data is still lacking. Considering the evidence
      available, most drugs elicit similar side effects from the same organ systems,
      and symptoms from the sublingual drug classes are probably less severe. However,
      a head-to-head comparison of safety and efficacy is lacking. 

PMID- 25968655
TI  - Muscarine-like compounds derived from a pyrolysis product of cellulose.
AB  - Cellulose represents a key component of a renewable biomass source, from which
      chiral compounds with a high added value in the application for the synthesis of
      potentially bioactive molecules can be obtained. The anhydrosugar (1R,5S)-1
      hydroxy-3,6-dioxa-bicyclo[3.2.1]octan-2-one (LAC), produced on the gram-scale by
      catalytic pyrolysis of cellulose, was used as a building block in the synthesis
      of five new enantiomerically pure muscarine-like products. The structures of the
      target compounds 4-8 showed different substituents at the C-2 and C-4 positions,
      but each of them had the same (2S,4R) configuration as the natural (+)-muscarine.
      A renewed interest in new muscarinic analogues is due to the design and synthesis
      of molecules exhibiting a higher selectivity for a specific muscarinic receptor
      and due to the development of effective agents in the treatment of Alzheimer's
      disease and other cognitive disorders. In this context, products 4-8 were
      investigated with respect to their binding affinity to human M1-M5 muscarinic
      acetylcholine receptors. The data indicated that compound 8, emerging as the most
      active in the series with values comparable to natural (+)-muscarine and a
      moderate selectivity in favor of the hM2 subtype receptor, also exhibited the
      highest stability during the interaction with the hM2 (3UON) subtype muscarinic
      receptor by using a docking calculation.

PMID- 25968656
TI  - DSM-5 substance use disorder: how conceptual missteps weakened the foundations of
      the addictive disorders field.

PMID- 25968657
TI  - Non-spherical gold nanoparticles trapped in optical tweezers: shape matters.
AB  - We present the results of a theoretical analysis focused on three-dimensional
      optical trapping of non-spherical gold nanoparticles using a tightly focused
      laser beam (i.e. optical tweezers). We investigate how the wavelength of the
      trapping beam enhances trapping stiffness and determines the stable orientation
      of nonspherical nanoparticles in the optical trap which reveals the optimal
      trapping wavelength. We consider nanoparticles with diameters being between 20 nm
      and 254 nm illuminated by a highly focused laser beam at wavelength 1064 nm and
      compare our results based on the coupled-dipole method with published theoretical
      and experimental data. We demonstrate that by considering the non-spherical
      morphology of the nanoparticle we can explain the experimentally observed three
      dimensional trapping of plasmonic nanoparticles with size higher than 170 nm.
      These results will contribute to a better understanding of the trapping and
      alignment of real metal nanoparticles in optical tweezers and their applications
      as optically controllable nanosources of heat or probes of weak forces and
      torques. 

PMID- 25968658
TI  - Devil's lens optical tweezers.
AB  - We demonstrate an optical tweezers using a laser beam on which is imprinted a
      focusing phase profile generated by a Devil's staircase fractal structure (Cantor
      set). We show that a beam shaped in this way is capable of stably trapping a
      variety of micron- and submicron-sized particles and calibrate the optical trap
      as a function of the control parameters of the fractal structure, and explain the
      observed variation as arising from radiation pressure exerted by unfocused parts
      of the beam in the region of the optical trap. Experimental results are
      complemented by calculation of the structure of the focus in the regime of high
      numerical aperture. 

PMID- 25968659
TI  - Fault detection in dielectric grid scatterers.
AB  - The problem of diagnosing a grid of small (in terms of the probing wavelength)
      dielectric scatterers is considered. The aim is to detect and locate possible
      defects occurring within a known grid when one (or more) scatterer is
      removed/missing (fault). The study is developed for the canonical case of a TM
      scalar two-dimensional geometry with the scatterers consisting of dielectric
      cylinders of small circular cross section. The scattering by a fault is modeled
      by relaying only to a priori information about the complete grid which leads to a
      numerically effective inversion procedures as the bulk of the numerical effort is
      to be done only once. Inversion is achieved by a truncated singular value
      decomposition scheme and results are provided in terms of closed form expressions
      for the probability of detection and of false alarm. This allows us to foreseen
      the achievable performance and to highlight the role of scattering configuration
      parameters. Numerical examples are also enclosed to corroborate theoretical
      outcomes. The case of two or more faults is considered as well. For such a case
      it is numerically shown that detection method still works well even though
      multiple scattering (occurring between faults) is neglected. 

PMID- 25968660
TI  - Novel approach for solid state cryocoolers.
AB  - Laser cooling in solids is based on anti-Stokes luminescence, via the
      annihilation of lattice phonons needed to compensate the energy of emitted
      photons, higher than absorbed ones. Usually the anti-Stokes process is obtained
      using a rare-earth active ion, like Yb. In this work we demonstrate a novel
      approach for optical cooling based not only to Yb anti-Stokes cycle but also to
      virtuous energy-transfer processes from the active ion, obtaining an increase of
      the cooling efficiency of a single crystal LiYF(4) (YLF) doped Yb at 5at.% with a
      controlled co-doping of 0.0016% Thulium ions. A model for efficiency enhancement
      based on Yb-Tm energy transfer is also suggested.

PMID- 25968661
TI  - Chirped lasers dispersion spectroscopy implemented with an electro-optical
      intensity modulator--signal strength and shapes under different experimental
      conditions.
AB  - Signals measured with Chirped Laser Dispersion Spectroscopy (CLaDS) setup
      implemented with an intensity modulator are analyzed. We investigate the signal
      amplitude dependence on the modulator bias voltage and the signal generator
      output power. Potential strategies for signal retrieval are discussed. We
      demonstrate that choosing a bias voltage, an RF generator output power and a
      demodulation frequency is critical for CLaDS and strongly affects its
      performance. 

PMID- 25968663
TI  - Spatial depolarization of light from the bulks: electromagnetic prediction.
AB  - The spatial depolarization of light emitted by heterogeneous bulks is predicted
      with exact electromagnetic theories. The sample microstructure and geometry is
      connected with partial polarization. 

PMID- 25968662
TI  - Phase control of squeezed vacuum states of light in gravitational wave detectors.
AB  - Quantum noise will be the dominant noise source for the advanced laser
      interferometric gravitational wave detectors currently under construction.
      Squeezing-enhanced laser interferometers have been recently demonstrated as a
      viable technique to reduce quantum noise. We propose two new methods of
      generating an error signal for matching the longitudinal phase of squeezed vacuum
      states of light to the phase of the laser interferometer output field. Both
      provide a superior signal to the one used in previous demonstrations of squeezing
      applied to a gravitational-wave detector. We demonstrate that the new signals are
      less sensitive to misalignments and higher order modes, and result in an improved
      stability of the squeezing level. The new signals also offer the potential of
      reducing the overall rms phase noise and optical losses, each of which would
      contribute to achieving a higher level of squeezing. The new error signals are a
      pivotal development towards realizing the goal of 6 dB and more of squeezing in
      advanced detectors and beyond. 

PMID- 25968664
TI  - Nonlinear optical response of low loss silicon germanium waveguides in the mid
      infrared.
AB  - We have investigated the nonlinear optical response of low loss Si(0.6)Ge(0.4) /
      Si waveguides in the mid-infrared wavelength range from 3.25- 4.75MUm using
      picosecond optical pulses. We observed and measured the three and four-photon
      absorption coefficients as well as the Kerr nonlinear refractive index. The
      dynamics of the spectral broadening suggests that, in addition to multiphoton
      absorption, the corresponding higher order nonlinear refractive phenomena also
      needs to be included when high optical pulse intensities are used at mid-infrared
      wavelengths in this material.

PMID- 25968665
TI  - Spectral barcodes by superposition of quasiperiodic refractive index profiles.
AB  - Averaging and shifting the refractive index profiles of quasiperiodic structure
      reveals the formation of several localized modes in the reflectivity spectrum and
      were used to generate different spectral barcodes. By associating the depth and
      wavelength of the observed resonant modes to the thickness and position of
      blackbars, respectively, the possibility to generate multiple codes has been
      shown. An experimental verification was carried out with multilayered dielectric
      porous silicon structures with reflectivity spectra revealing unique photonic
      fingerprints. 

PMID- 25968666
TI  - Towards integration of a liquid-filled fiber capillary for supercontinuum
      generation in the 1.2-2.4 MUm range.
AB  - We demonstrate supercontinuum generation in unspliced as well as in integrated
      CS(2)-filled capillary fibers at different pump wavelengths of 1030 nm, 1510 nm,
      and 1685 nm. A novel method for splicing a liquid-filled capillary fiber to a
      standard single-mode optical fiber is presented. This method is based on
      mechanical splicing using a direct-laser written polymer ferrule using a
      femtosecond two-photon polymerization process. We maintain mostly single-mode
      operation despite the multi-mode capability of the liquid-filled capillaries. The
      generated supercontinua exhibit a spectral width of over 1200 nm and 1000 nm for
      core diameters of 5 MUm and 10 MUm, respectively. This is an increase of more
      than 50 percent compared to previously reported values in the literature due to
      improved dispersion properties of the capillaries.

PMID- 25968667
TI  - Equivalent-nanocircuit-theory-based design to infrared broad band-stop filters.
AB  - We theoretically introduced a design paradigm and tool by extending the circuit
      functionalities from radio frequency to near infrared domain, and a broad band
      stop filter, is successfully demonstrated by cascading triple layers of nano
      square arrays. The feasibility is confirmed by its consistency with the rigorous
      FDTD calculation. Moreover, such a third-order Butterworth filter is not only
      insensitive to the incident angle and but also to input light's polarization. The
      new paradigm forms a theoretical foundation for designing optical devices and
      also enriches the classic circuit operations at the optical frequency region. 

PMID- 25968668
TI  - Dual-mode plasmonic nanorod type antenna based on the concept of a trapped
      dipole.
AB  - In this paper we theoretically investigate the feasibility of creating a dual
      mode plasmonic nanorod antenna. The proposed design methodology relies on
      adapting to optical wavelengths the principles of operation of trapped dipole
      antennas, which have been widely used in the low MHz frequency range. This type
      of antenna typically employs parallel LC circuits, also referred to as "traps",
      which are connected along the two arms of the dipole. By judiciously choosing the
      resonant frequency of these traps, as well as their position along the arms of
      the dipole, it is feasible to excite the lambda/2 resonance of both the original
      dipole as well as the shorter section defined by the length of wire between the
      two traps. This effectively enables the dipole antenna to have a dual-mode of
      operation. Our analysis reveals that the implementation of this concept at the
      nanoscale requires that two cylindrical pockets (i.e. loading volumes) be
      introduced along the length of the nanoantenna, inside which plasmonic core-shell
      particles are embedded. By properly selecting the geometry and constitution of
      the core-shell particle as well as the constitution of the host material of the
      two loading volumes and their position along the nanorod, the equivalent effect
      of a resonant parallel LC circuit can be realized. This effectively enables a
      dual-mode operation of the nanorod antenna. The proposed methodology introduces a
      compact approach for the realization of dual-mode optical sensors while at the
      same time it clearly illustrates the inherent tuning capabilities that core-shell
      particles can offer in a practical framework. 

PMID- 25968669
TI  - Femtosecond laser direct writing of single mode polymer micro ring laser with
      high stability and low pumping threshold.
AB  - We have demonstrated an optically pumped polymer microring laser fabricated by
      two photon polymerization (TPP) of SU-8. The gain medium is an organic dye
      (Rhodamine B) doped in SU-8, and the laser cavity is a double coupled microring
      structure. Single mode lasing was obtained from the two coupled rings each with
      30 um and 29 um radii using Vernier effect. Low laser threshold of 0.4 uJ/mm(2)
      is achieved using 1 um wide polymer waveguides and the quality factor is greater
      than 10(4) at 612.4 nm wavelength. The lasing remained stable with pump energies
      from threshold to energies as high as 125 times the threshold.

PMID- 25968670
TI  - Nonlinear inverse synthesis technique for optical links with lumped
      amplification.
AB  - The nonlinear inverse synthesis (NIS) method, in which information is encoded
      directly onto the continuous part of the nonlinear signal spectrum, has been
      proposed recently as a promising digital signal processing technique for
      combating fiber nonlinearity impairments. However, because the NIS method is
      based on the integrability property of the lossless nonlinear Schrodinger
      equation, the original approach can only be applied directly to optical links
      with ideal distributed Raman amplification. In this paper, we propose and assess
      a modified scheme of the NIS method, which can be used effectively in standard
      optical links with lumped amplifiers, such as, erbium-doped fiber amplifiers
      (EDFAs). The proposed scheme takes into account the average effect of the fiber
      loss to obtain an integrable model (lossless path-averaged model) to which the
      NIS technique is applicable. We found that the error between lossless path
      averaged and lossy models increases linearly with transmission distance and input
      power (measured in dB). We numerically demonstrate the feasibility of the
      proposed NIS scheme in a burst mode with orthogonal frequency division
      multiplexing (OFDM) transmission scheme with advanced modulation formats (e.g.,
      QPSK, 16QAM, and 64QAM), showing a performance improvement up to 3.5 dB; these
      results are comparable to those achievable with multi-step per span digital back
      propagation. 

PMID- 25968671
TI  - High birefringence photonic crystal fiber with high nonlinearity and low
      confinement loss.
AB  - A particular photonic crystal fiber (PCF) designed with all circle air holes is
      proposed. Its characteristics are studied by full-vector finite element method
      (FEM) with anisotropic perfectly matched layer (PML). The simulation results
      indicated that the proposed PCF can realize high birefringence (up to 10(-2)),
      high nonlinearity (50W(-1).km(-1) and 68W(-1).km(-1) in X and Y polarizations
      respectively) and low confinement loss (less than 10(-3)dB/km at 1.55um
      wavelength).

PMID- 25968672
TI  - Scanning metallic nanosphere microscopy for vectorial profiling of optical focal
      spots.
AB  - Recent years have witnessed fast progress in the development of spatially variant
      states of polarization under high numerical aperture focusing, and intensive
      exploration of their applications. We report a vectorial, broadband, high
      contrast and subwavelength resolution method for focal spot profiling. In this
      experiment, a 100 nm diameter gold nanosphere on a silica aerogel substrate is
      raster scanned across the focal spots, and the orthogonal polarization components
      can be obtained simultaneously by measuring the scattering far field in a
      confocal manner. The metallic-nanosphere-on-aerogel structure ensures negligible
      distortion to the focal spots, low crosstalk between orthogonal polarization
      components (1/39 in experiment), and a low level background noise (1/80 of peak
      intensity in experiment), while high contrast imaging is not limited by the
      resonance bandwidth. 

PMID- 25968673
TI  - Tunable graphene-coated spiral dielectric lens as a circular polarization
      analyzer.
AB  - We propose a tunable circular polarization analyzer based on a graphene-coated
      spiral dielectric lens. Spatially separated solid dot shape (or donut shape)
      field can be achieved if the geometric shape of analyzer and incident circular
      polarization possess the opposite (or same) chirality. Moreover, distinct from
      the narrow working bandwidth of a traditional circular polarization analyzer, the
      focusing and defocusing effects in the analyzer are independent of the chemical
      potential of graphene, and depend only on the dielectric permittivities and the
      grating occupation ratio. Combined with the strong tunability of graphene
      plasmons, the operation wavelength of analyzer can be tuned by adjusting the
      graphene chemical potential without degrading the performance. The proposed
      analyzer could be used in applications in chemistry or biology, such as analyzing
      the physiological properties of chiral molecules based on circular polarization. 

PMID- 25968674
TI  - All-optical 2-bit header recognition and packet switching using polarization
      bistable VCSELs.
AB  - We propose and evaluate an all-optical 2-bit header recognition and packet
      switching method using two 1.55-um polarization bistable vertical-cavity surface
      emitting lasers (VCSELs) and three optical switches. Polarization bistable VCSELs
      acted as flip-flop devices by using AND-gate operations of the header and set
      pulses, together with the reset pulses. Optical packets including 40-Gb/s non
      return-to-zero pseudo-random bit-sequence payloads were successfully sent to one
      of four ports according to the state of two bits in the headers with a 4-bit 500
      Mb/s return-to-zero format. The input pulse powers were 17.2 to 31.8 dB lower
      than the VCSEL output power. We also examined an extension of this method to
      multi-bit header recognition and packet switching. 

PMID- 25968675
TI  - Multi-wavelength holography with a single spatial light modulator for ultracold
      atom experiments.
AB  - We demonstrate a method to independently and arbitrarily tailor the spatial
      profile of light of multiple wavelengths and we show possible applications to
      ultracold atoms experiments. A single spatial light modulator is programmed to
      create a pattern containing multiple spatially separated structures in the
      Fourier plane when illuminated with a single wavelength. When the modulator is
      illuminated with overlapped laser beams of different wavelengths, the position of
      the structures is wavelength-dependent. Hence, by designing their separations
      appropriately, a desired overlap of different structures at different wavelengths
      is obtained. We employ regional phase calculation algorithms and demonstrate
      several possible experimental scenarios by generating light patterns with 670 nm,
      780 nm and 1064 nm laser light which are accurate to the level of a few percent.
      This technique is easily integrated into cold atom experiments, requiring little
      optical access. 

PMID- 25968676
TI  - Dark-hollow optical beams with a controllable shape for optical trapping in air.
AB  - A technique for generating dark-hollow optical beams (DHOBs) with a controllable
      cross-sectional intensity distribution is proposed and studied both theoretically
      and experimentally. Superimposed Bessel beams were used to generate such DHOBs.
      Variation of individual beam parameters enables the generation of Bessel-like non
      diffracting beams. This technique allows the design of transmission functions for
      elements that shape both non-rotating and rotating DHOBs. We demonstrate
      photophoresis-based optical trapping and manipulation of absorbing air-borne
      nanoclusters with such beams. 

PMID- 25968677
TI  - High performance 2150 nm-emitting InAs/InGaAs/InP quantum well lasers grown by
      metalorganic vapor phase epitaxy.
AB  - We demonstrate high performance 2150 nm InAs/InGaAs/InP quantum well (QW) lasers
      grown by metalorganic vapor phase epitaxy. The laser structure consists of two
      InAs/InGaAs QWs, with a 30 MUm-wide ridge waveguide and two cleaved cavity
      facets. The continuous wave operation at room temperature (RT) is achieved, with
      an output power of larger than 160 mW per facet and with a low threshold current
      density of 90.4 A/cm(2) per QW derived for the infinite cavity length. Under
      pulse injection mode, the maximal peak power per facet is as high as 1.35 W. By
      varying the cavity length, the lasing wavelength can be tuned in a range from
      2142 nm to 2154 nm. Moreover, the highest operating temperature reaches up to 100
      degrees C, and characteristic temperatures are 50 K (T(0)) and 132 K (T(1)) in
      the temperature range of 20-70  degrees C, respectively.

PMID- 25968678
TI  - Ultrahigh-sensitivity sensors based on thin-film coated long period gratings with
      reduced diameter, in transition mode and near the dispersion turning point.
AB  - The mode transition and the dispersion turning point have been explored for
      optimization of thin-film coated long period fiber gratings during the last
      years. In this work and additional parameter, the cladding diameter, is combined
      with the other two phenomena for improving the sensitivity to the surrounding
      medium refractive index. The numerical data obtained were calculated with a
      method based on the exact calculation of core and cladding modes and the
      utilization of coupled mode theory. A sensitivity 143 * 10(3) nm/RIU is obtained,
      the highest reported so far with long period fiber gratings.

PMID- 25968679
TI  - DC-offset-free homodyne interferometer and its nonlinearity compensation.
AB  - This study presents an analysis of the cyclic nonlinearity in the homodyne
      interferometer starting from the interference principle. We present the design
      for an enhanced homodyne interferometer without DC offset, for which the
      nonlinearity model will not be influenced by the intensity of the measurement
      beam. Our experimental results show that the enhanced interferometer can suppress
      the nonlinearity to less than 0.5 nm with a system calibration involving gain
      adjustment and phase-correction methods. 

PMID- 25968680
TI  - Polarization-interleave-multiplexed discrete multi-tone modulation with direct
      detection utilizing MIMO equalization.
AB  - Discrete multi-tone (DMT) modulation is an attractive modulation format for short
      reach applications to achieve the best use of available channel bandwidth and
      signal noise ratio (SNR). In order to realize polarization-multiplexed DMT
      modulation with direct detection, we derive an analytical transmission model for
      dual polarizations with intensity modulation and direct diction (IM-DD) in this
      paper. Based on the model, we propose a novel polarization-interleave-multiplexed
      DMT modulation with direct diction (PIM-DMT-DD) transmission system, where the
      polarization de-multiplexing can be achieved by using a simple multiple-input
      multiple-output (MIMO) equalizer and the transmission performance is optimized
      over two distinct received polarization states to eliminate the singularity issue
      of MIMO demultiplexing algorithms. The feasibility and effectiveness of the
      proposed PIM-DMT-DD system are investigated via theoretical analyses and
      simulation studies. 

PMID- 25968681
TI  - Directional crystallization of polymer molecules through solvent annealing on a
      patterned substrate.
AB  - Multi-crystalline fibers of poly (3-hexylthiophene) (P3HT) have been grown on a
      patterned substrate through annealing the spin-coated film in the solvent of 1,5
      pentanediol at 120  degrees C. The large-area patterns of photoresist grating
      have been fabricated by interference lithography, enabling growth of crystal
      fibers in a length scale of centimeters. The produced organic crystal fibers were
      characterized by microscopic, spectroscopic, and electrical conductivity
      performances. Mechanisms for the crystallization processes were investigated. 

PMID- 25968682
TI  - Solitons of four-wave mixing in competing cubic-quintic nonlinearity.
AB  - We experimentally investigate the soliton formation and dynamics in the nonlinear
      propagation of the generated signal and probe beams in four-wave mixing (FWM)
      process with atomic coherence in a three-level atomic system, under the
      competition between focusing and defocusing nonlinearities, as well as between
      gain and dissipation, due to the third- and fifth-order nonlinear
      susceptibilities with opposite signs. With multi-parameter controllability and
      nonlinear competition in the system, fundamental, dipole, and azimuthally
      modulated vortex FWM solitons can transform mutually from one to the other. Such
      investigations have potential applications in optical pattern formation and
      control, and all-optical communication. 

PMID- 25968683
TI  - Label-free sensitivity of long-period gratings enhanced by atomic layer deposited
      TiO(2) nano-overlays.
AB  - In this paper, we discuss an impact of thin titanium dioxide (TiO(2)) coatings on
      refractive index (RI) sensitivity and biofunctionalization of long-period
      gratings (LPGs). The TiO(2) overlays on the LPG surfaces have been obtained using
      atomic layer deposition (ALD) method. This method allows for a deposition of
      conformal, thickness-controlled, with well-defined optical properties, and high
      RI thin films which are highly desired for optical fiber sensors. It has been
      found that for LPGs working at a dispersion turning point of higher order
      cladding modes only tens of nanometers of TiO(2) overlay thickness allow to
      obtain cladding mode transition effect, and thus significant improvement of RI
      sensitivity. When the TiO(2) overlay thickness reaches 70 nm, it is possible to
      obtain RI sensitivity exceeding 6200 nm/RIU in RI range where label-free sensors
      operate. Moreover, LPGs with TiO(2)-enhanced RI sensitivity have shown improved
      sensitivity to bacteria endotoxin (E. coli B lipopolysaccharide) detection, when
      TiO(2) surface is functionalized with endotoxin binding protein (adhesin) of T4
      bacteriophage.

PMID- 25968684
TI  - Intracavity Raman conversion of a red semiconductor disk laser using diamond.
AB  - We demonstrate a diamond Raman laser intracavity-pumped by a red semiconductor
      disk laser (~675 nm) for laser emission at around 740 nm. Output power up to 82
      mW of the Stokes-shifted field was achieved, limited by the available pump power,
      with an output coupling of 1.5%. We also report wavelength tuning of the diamond
      Raman laser over 736 - 750 nm. 

PMID- 25968685
TI  - Quantum cascade lasers: from tool to product.
AB  - The quantum cascade laser (QCL) is an important laser source in the mid-infrared
      and terahertz frequency range. The past twenty years have witnessed its
      tremendous development in power, wall plug efficiency, frequency coverage and
      tunability, beam quality, as well as various applications based on QCL
      technology. Nowadays, QCLs can deliver high continuous wave power output up to
      5.1 W at room temperature, and cover a wide frequency range from 3 to 300 MUm by
      simply varying the material components. Broadband heterogeneous QCLs with a broad
      spectral range from 3 to 12 MUm, wavelength agile QCLs based on monolithic
      sampled grating design, and on-chip beam QCL combiner are being developed for the
      next generation tunable mid-infrared source for spectroscopy and sensing.
      Terahertz sources based on nonlinear generation in QCLs further extend the
      accessible wavelength into the terahertz range. Room temperature continuous wave
      operation, high terahertz power up to 1.9 mW, and wide frequency tunability form
      1 to 5 THz makes this type of device suitable for many applications in terahertz
      spectroscopy, imaging, and communication. 

PMID- 25968686
TI  - Equivalence of data fusion and simultaneous retrieval.
AB  - A new method for the data fusion of atmospheric vertical profiles, referred to as
      complete fusion, is presented. Using the measurements of the MIPAS instrument,
      the performance of the method is compared with those of weighted and arithmetic
      means. The complete fusion perfectly reproduces the results of the simultaneous
      retrieval with equal error estimates and number of degrees of freedom, while
      arithmetic and weighted means have relatively low vertical resolution and differ
      from the simultaneous retrieval by more than their errors. In addition the
      problem posed in this context by systematic errors is analyzed and alleviating
      procedures are considered. 

PMID- 25968687
TI  - 1310 nm hybrid InP/InGaAsP on silicon distributed feedback laser with high side
      mode suppression ratio.
AB  - We report on the design, fabrication and performance of a hetero-integrated III-V
      on silicon distributed feedback lasers (DFB) at 1310 nm based on direct bonding
      and adiabatic coupling. The continuous wave (CW) regime is achieved up to 55 
      degrees C as well as mode-hop-free operation with side-mode suppression ratio
      (SMSR) above 55 dB. At room temperature, the current threshold is 36 mA and the
      maximum coupled power in the silicon waveguide is 22 mW. 

PMID- 25968688
TI  - High energy green nanosecond and picosecond pulse delivery through a negative
      curvature fiber for precision micro-machining.
AB  - In this paper we present an anti-resonant guiding, low-loss Negative Curvature
      Fiber (NCF) for the efficient delivery of high energy short (ns) and ultrashort
      (ps) pulsed laser light in the green spectral region. The fabricated NCF has an
      attenuation of 0.15 dB/m and 0.18 dB/m at 532 nm and 515 nm respectively, and
      provided robust transmission of nanosecond and picosecond pulses with energies of
      0.57 mJ (10.4 kW peak power) and 30 uJ (5 MW peak power) respectively. It
      provides single-mode, stable (low bend-sensitivity) output and maintains spectral
      and temporal properties of the source laser beam. The practical application of
      fiber-delivered pulses has been demonstrated in precision micro-machining and
      marking of metals and glass. 

PMID- 25968689
TI  - Revealing carrier-envelope phase through frequency mixing and interference in
      frequency resolved optical gating.
AB  - We demonstrate that full temporal characterisation of few-cycle electromagnetic
      pulses, including retrieval of the carrier envelope phase (CEP), can be directly
      obtained from Frequency Resolved Optical Gating (FROG) techniques in which the
      interference between non-linear frequency mixing processes is resolved. We derive
      a framework for this scheme, defined Real Domain FROG (ReD-FROG), for the cases
      of interference between sum and difference frequency components and between
      fundamental and sum / difference frequency components. A successful numerical
      demonstration of ReD-FROG as applied to the case of a self-referenced measurement
      is provided. A proof-of-principle experiment is performed in which the CEP of a
      single-cycle THz pulse is accurately obtained and demonstrates the possibility
      for THz detection beyond optical probe duration limitations inherent to electro
      optic sampling. 

PMID- 25968690
TI  - Powers of the degree of coherence.
AB  - We establish conditions under which a legitimate degree of coherence of a
      statistically stationary beam-like field raised to a power results in a novel
      legitimate degree of coherence. The general results and examples relate to scalar
      beams having uniform and non-uniform correlations. 

PMID- 25968691
TI  - All-optical Q-switching limiter for high-power gigahertz modelocked diode-pumped
      solid-state lasers.
AB  - Passively modelocked diode-pumped solid-state lasers (DPSSLs) with pulse
      repetition rates in the gigahertz regime suffer from an increased tendency for Q
      switching instabilities. Low saturation fluence intracavity saturable absorbers -
      such as the semiconductor saturable absorber mirrors (SESAMs) - can solve this
      problem up to a certain average output power limited by the onset of SESAM
      damage. Here we present a passive stabilization mechanism, an all-optical Q
      switching limiter, to reduce the impact of Q-switching instabilities and increase
      the potential output power of SESAM modelocked lasers in the gigahertz regime.
      With a proper cavity design a Kerr lens induced negative saturable absorber
      clamps the maximum fluence on the SESAM and therefore limits the onset of Q
      switching instabilities. No critical cavity alignment is required because this Q
      switching limiter acts well within the cavity stability regime. Using a proper
      cavity design, a high-power diode-pumped Yb:CALGO solid-state laser generated sub
      100 fs pulses with an average output power of 4.1 W at a pulse repetition rate of
      5 GHz. With a pulse duration of 96 fs we can achieve a peak power as high as 7.5
      kW directly from the SESAM modelocked laser oscillator without any further
      external pulse amplification and/or pulse compression. We present a quantitative
      analysis of this Kerr lens induced Q-switching limiter and its impact on
      modelocked operation. Our work provides a route to compact high-power multi
      gigahertz frequency combs based on SESAM modelocked diode-pumped solid-state
      lasers without any additional external amplification or pulse compression. 

PMID- 25968692
TI  - Scalar diffraction modeling of multispectral forward scatter patterns from
      bacterial colonies.
AB  - A theoretical model for spectral forward scatter patterns from a bacterial colony
      based on elastic light scatter is presented. The spectral forward scatter
      patterns are computed by scalar diffraction theory, and compared with
      experimental results of three discrete wavelengths (405 nm, 635 nm, and 904 nm).
      To provide quantitative analysis, spectral dependence of diffraction ring width,
      gap, maxima, minima, and the first deflection point are monitored. Both model and
      experiment results show an excellent agreement; a longer wavelength induces a
      wider ring width, a wider ring gap, a smaller pattern size, and smaller numbers
      of rings. Further analysis using spatial fast Fourier transform (SFFT) shows a
      good agreement; the spatial frequencies are increasing towards the inward
      direction, and the slope is inversely proportional to the incoming wavelength. 

PMID- 25968693
TI  - Exploiting the dispersion of the double-negative-index fishnet metamaterial to
      create a broadband low-profile metallic lens.
AB  - Metamaterial lenses with close values of permittivity and permeability usually
      display low reflection losses at the expense of narrow single frequency
      operation. Here, a broadband low-profile lens is designed by exploiting the
      dispersion of a fishnet metamaterial together with the zoning technique. The lens
      operates in a broadband regime from 54 GHz to 58 GHz, representing a fractional
      bandwidth ~7%, and outperforms Silicon lenses between 54 and 55.5 GHz. This
      broadband operation is demonstrated by a systematic analysis comprising Huygens
      Fresnel analytical method, full-wave numerical simulations and experimental
      measurements at millimeter waves. For demonstrative purposes, a detailed study of
      the lens operation at two frequencies is done for the most important lens
      parameters (focal length, depth of focus, resolution, radiation diagram).
      Experimental results demonstrate diffraction-limited ~0.5lambda transverse
      resolution, in agreement with analytical and numerical calculations. In a lens
      antenna configuration, a directivity as high as 16.6 dBi is achieved. The
      different focal lengths implemented into a single lens could be potentially used
      for realizing the front end of a non-mechanical zoom millimeter-wave imaging
      system. 

PMID- 25968694
TI  - Dual view capsule endoscopic lens design.
AB  - A dual view capsule endoscopic (DVCE) lens is proposed with front view and back
      view functions. This is a hybrid lens with a catadioptric mirror and an
      aspherical surface to support both view functions. The field of view (FOV) for
      the front view function is 90 degrees. The FOV for the back view function is 260
      to 290 degrees. The TV distortion for the front view and back view function is
      under 30% and 25%. The corner relative illuminations for the two view functions
      are above 0.53. The Modulation Transfer Function (MTF) performance at the Nyquist
      Frequency for the two view functions can be kept above 0.35, even under tolerance
      they can remain above 0.2. Moreover, the telecentric conditions at the image
      plane of the DVCE system can support constant magnification through focusing.
      This condition can reduce the measurement error by slightly defocusing of the
      lens. Thus, the two view functions can offer physicians a wide viewing angle to
      deal with lesions over the fold. 

PMID- 25968695
TI  - Surface plasmon resonance sensor based on D-shaped microstructured optical fiber
      with hollow core.
AB  - To solve the phase matching and analyte filling problems in the microstructured
      optical fiber (MOF)-based surface plasmon resonance (SPR) sensors, we present the
      D-shaped hollow core MOF-based SPR sensor. The air hole in the fiber core can
      lower the refractive index of a Gaussian-like core mode to match with that of a
      plasmon mode. The analyte is deposited directly onto the D-shaped flat surface
      instead of filling the fiber holes. We numerically investigate the effect of the
      air hole in the core on the SPR sensing performance, and identify the sensor
      sensitivity on wavelength, amplitude and phase. This work allows us to determine
      the feasibility of using the D-shaped hollow-core MOFs to develop a high
      sensitivity, real-time and distributed SPR sensor. 

PMID- 25968696
TI  - Broadband molecular sensing with a tapered spoof plasmon waveguide.
AB  - Unambiguous identification of low concentration chemical mixtures can be
      performed by broadband enhanced infrared absorption (BEIRA). Here we propose and
      numerically study a corrugated parallel plate waveguide (CPPW) with gradient
      grooves which is capable of directly converting transmission modes to surface
      plasmon modes and could hence serve as a powerful chemical sensor. Such a
      waveguide can be designed to exhibit a wide pass band covering an extended
      portion of a molecule absorption spectrum. Broadband sensing of toluene and
      ethanol thin layers is demonstrated by calculating the transmission coefficient
      of the waveguide and is shown to correspond exactly to their infrared spectra. In
      addition, the upper limit and the lower limit of the bandgap are mainly dependent
      on the minimum and maximum groove height, respectively, which provide an
      effective way of tuning the working frequency of the device in order to support
      surface plasmon modes within a desired frequency range according to a specific
      application. 

PMID- 25968697
TI  - Modelling and optimization of continuous-wave external cavity Raman lasers.
AB  - We report an analytical model describing power and efficiency of a 23 W quasi
      continuous-wave diamond Raman laser. The model guides the optimization of the
      first Stokes output power as a function of resonator and crystal parameters. We
      show that, in the limit of a weak thermal lens, efficient operation requires
      strong focussing, low output coupling and low-absorption crystals. Efficient
      damage-free operation at higher pump powers is predicted to benefit greatly from
      increased optimum output couplings that act to limit the intracavity Stokes
      field. 

PMID- 25968698
TI  - Sound emission from the gas of molecular superrotors.
AB  - We use an optical centrifuge to deposit a controllable amount of rotational
      energy into dense molecular ensembles. Subsequent rotation-translation energy
      transfer, mediated by thermal collisions, results in the localized heating of the
      gas and generates strong sound wave, clearly audible to the unaided ear. For the
      first time, the amplitude of the sound signal is analyzed as a function of the
      experimentally measured rotational energy and linear proportionality between the
      two observables is established. 

PMID- 25968699
TI  - Physical insight toward electric field enhancement at nodular defects in optical
      coatings.
AB  - Although the finite-difference time-domain (FDTD) technique has been prevailingly
      used to calculate the electric field intensity (EFI) enhancement at nodular
      defects in high-reflection (HR) coatings, the physical insight as to how the
      nodular features contribute to the intensified EFI is not explicitly revealed
      yet, which in turn limits the solutions that improve the laser-induced damage
      threshold (LIDT) of nodules by decreasing the EFI enhancement. Here, a simplified
      model is proposed to describe the intensified EFI in nodules: 1) the nodule works
      as a microlens and its focal length can be predicted using a simple formula, 2)
      the portion of incident light that penetrates through the HR coating can be
      estimated by knowing the angular dependent transmittance (ADT) of the nodule, 3)
      strong EFI enhancement is created when the focal point is within the nodule and
      simultaneously a certain portion of light penetrates to the focal position. In
      the light of the proposed model, a broadband HR coating was used to reduce the
      EFI enhancement at the seed by a factor about 10, which leads to a 20 times
      increment of the LIDT. This work therefore not only deepens the physical
      understanding of EFI enhancement at nodules but also provides a new way to
      increase the LIDT of multilayer reflective optics. 

PMID- 25968700
TI  - One exposure processing to fabricate spiral phase plate with continuous surface.
AB  - An economical method for fabricating spiral phase plate (SPP) with continuous
      surface is proposed in this paper. We use an interval to quantize a three
      dimensional surface of an SPP into two dimensional bars to form a binary mask.
      The exposure dose can be precisely distributed through this mask in the exposure
      process. We discuss the select criterion of the quantization interval and the
      fabricating processes of SPP in detail. In the results, we present the
      fabrication of four kinds of high quality SPPs with different topological
      charges. The morphology analysis and the corresponding optical measurements
      verify the reliability of our fabrication method. 

PMID- 25968701
TI  - Simple and aberration-free 4color-STED--multiplexing by transient binding.
AB  - Most fluorescence microscopy experiments today require a multicolor-capable
      setup, e.g. to study the interaction between different proteins. Multicolor
      capabilities are also well desirable for superresolution images. However,
      especially for STED (Stimulated Emission Depletion) microscopy, which requires
      two laser lines for a single color, multicolor imaging is technically
      challenging. Here we present a straightforward, easy-to-implement method to
      extend a single-color fluorescence (STED) microscope to a multichannel microscope
      without the need of modifying the optical setup. Therefore, we use a labeling
      technique based on complementary DNA sequences: a single-stranded short DNA
      sequence is attached to each structure to be imaged, different colors for
      labeling different features are represented by different sequences. Within the
      imaging process, the corresponding complementary sequence labeled with an organic
      fluorophore is added and transiently binds to the corresponding structure. After
      imaging, the labeled sequence is washed away and replaced by a second
      fluorescently labeled DNA strand complementary to the sequence bound to another
      feature. This way, multiplexing is achieved using only one arbitrary fluorophore,
      therefore aberrations are avoided. 

PMID- 25968702
TI  - Influence of laser linewidth and polarization modulator length on polarization
      shift keying for free space optical communication.
AB  - Modulating signal with polarization modulator (PolM) is the simplest method for
      polarization shift keying (PolSK) in free space optical communication. However,
      this method has an intrinsic drawback on degree of polarization (DOP) reduction
      for the existence of polarization mode dispersion (PMD) in PolM. In this work, we
      analyze this change of DOP and its influence on PolSK using coherency matrix. We
      demonstrate that the decrease of DOP after PolM will generate extra loss and bit
      error ratio (BER) for PolSK communication, while this loss and BER will aggravate
      with the increase of laser linewidth and PolM length. For a practical PolSK
      system, laser linewidth should be less than 0.008nm. 

PMID- 25968703
TI  - Micro particle launcher/cleaner based on optical trapping technology.
AB  - Efficient and controllable launching function of an optical tweezers is a
      challenging task. We present and demonstrate a novel single fiber optical
      tweezers which can trap and launch (clean) a target polystyrene (PS) microsphere
      (diameter~10MUm) with independent control by using two wavelengths beams: 980nm
      and 1480nm. We employ 980nm laser beam to trap the target PS microsphere by
      molding the fiber tip into a special tapered-shape; and we employ 1480nm laser
      beam to launch the trapped PS microsphere with a certain velocity by using the
      thermophoresis force generated from the thermal effect due to the high absorption
      of the 1480nm laser beams in water. When the launching force is smaller than the
      trapping force, the PS microsphere will be trapped near the fiber tip, and the
      launching force will blow away other PS microspheres in the workspace realizing
      the cleaning function; When the launching force is larger than the trapping
      force, the trapped PS microsphere will be launched away from the fiber tip with a
      certain velocity and towards a certain direction, realizing the launching
      function. The launching velocity, acceleration and the distance can be measured
      by detecting the interference signals generated from the PS microsphere surface
      and the fiber tip end-face. This PS microsphere launching and cleaning functions
      expanded new features of single fiber optical tweezers, providing for the
      possibility of more practical applications in the micro manipulation research
      fields. 

PMID- 25968704
TI  - Influence of photo-inscription conditions on the radiation-response of fiber
      Bragg gratings.
AB  - We compared the sensitivity to X-rays of several fiber Bragg gratings (FBGs)
      written in the standard telecommunication fiber Corning SMF28 with different
      techniques. Standard gratings were manufactured with phase-mask and UV lasers,
      continuum wave (cw) at 244 nm or pulsed in the nanosecond domain at 248 nm, in a
      pre-hydrogenated fiber. Others gratings were written by exposures to a
      femtosecond IR-laser (800 nm), with both phase-mask and point by point
      techniques. The response of these FBGs was studied under X-rays at room
      temperature and 100 degrees C, by highlighting their similarities and
      differences. Independently of the inscription technique, the two types of fs-FBGs
      have showed no big difference up to 1 MGy(SiO(2)) dose. A discussion on the
      causes of the radiation-induced peak change is also reported.

PMID- 25968705
TI  - Wide-angle, polarization-independent and dual-band infrared perfect absorber
      based on L-shaped metamaterial.
AB  - We propose a wide-angle, polarization-independent and dual-band infrared perfect
      metamaterial absorber made of double L-shaped gold patches on a dielectric spacer
      and opaque gold ground layer. Numerical and experimental results demonstrate that
      the absorber has two near-unity absorption peaks, which are result from magnetic
      polariton modes generated at two different resonant wavelengths. In addition, the
      proposed structure also shows good absorption stability in a wide range of
      incident anglesthetafor both TE and TM incidences at azimuthal angle phi = 0
      degrees . Moreover, we demonstrate that such structure has good absorption
      stability for a wide range of azimuthal angles due to the excitation of
      perpendicular magnetic polariton modes within the asymmetric double L-shaped
      structure. Such structure will assist in designing magnetic polaritons absorbing
      element for infrared spectroscopy and imaging. 

PMID- 25968706
TI  - Positive and negative phototunability of chalcogenide (AMTIR-1) microdisk
      resonator.
AB  - We demonstrate externally photo-induced partially-reversible tuning of the
      resonance of a microdisk made of AMTIR-1 (Ge(33)As(12)Se(55)). We have achieved
      for the first time, to the best of our knowledge, both positive and negative
      shift in a microresonator with external tuning. A positive resonance shift of 1
      nm and a negative resonance shift of 0.5 nm on a single microdisk has been
      measured. We have found that this phenomenon is due to initial photo-expansion of
      the microdisk followed by the photo-bleaching of the AMTIR-1. The observed shifts
      and the underlying phenomenon is controllable by varying the illumination power
      (i.e. the low power illumination suppresses the photobleaching process). We
      measure a loaded quality factor of 1.2x10(5) at 1550nm (limited by the measuring
      instrument). This holds promise for non-contact low power reversible-tunning of
      photonic circuit elements.

PMID- 25968707
TI  - Cascaded stimulated polariton scattering in a Mg:LiNbO(3) terahertz laser.
AB  - Cascaded Stimulated Polariton Scattering (SPS) to the fourth-Stokes order is
      observed experimentally in an intracavity THz polariton laser utilising
      Mg:LiNbO(3). The performance of the cascaded laser is presented, the origin of
      the cascaded fields is explained and compared to theory, and the potential
      consequences for using cascading to enhance the THz output from this type of
      device are discussed.

PMID- 25968708
TI  - Modeling focusing Gaussian beams in a turbid medium with Monte Carlo simulations.
AB  - Monte Carlo techniques are the gold standard for studying light propagation in
      turbid media. Traditional Monte Carlo techniques are unable to include wave
      effects, such as diffraction; thus, these methods are unsuitable for exploring
      focusing geometries where a significant ballistic component remains at the focal
      plane. Here, a method is presented for accurately simulating photon propagation
      at the focal plane, in the context of a traditional Monte Carlo simulation. This
      is accomplished by propagating ballistic photons along trajectories predicted by
      Gaussian optics until they undergo an initial scattering event, after which, they
      are propagated through the medium by a traditional Monte Carlo technique. Solving
      a known problem by building upon an existing Monte Carlo implementation allows
      this method to be easily implemented in a wide variety of existing Monte Carlo
      simulations, greatly improving the accuracy of those models for studying dynamics
      in a focusing geometry. 

PMID- 25968709
TI  - High-order optical vortex position detection using a Shack-Hartmann wavefront
      sensor.
AB  - Optical vortex (OV) beams have null-intensity singular points, and the
      intensities in the region surrounding the singular point are quite low. This low
      intensity region influences the position detection accuracy of phase singular
      point, especially for high-order OV beam. In this paper, we propose a new method
      for solving this problem, called the phase-slope-combining correlation matching
      method. A Shack-Hartmann wavefront sensor (SH-WFS) is used to measure phase slope
      vectors at lenslet positions of the SH-WFS. Several phase slope vectors are
      combined into one to reduce the influence of low-intensity regions around the
      singular point, and the combined phase slope vectors are used to determine the OV
      position with the aid of correlation matching with a pre-calculated database.
      Experimental results showed that the proposed method works with high accuracy,
      even when detecting an OV beam with a topological charge larger than six. The
      estimated precision was about 0.15 in units of lenslet size when detecting an OV
      beam with a topological charge of up to 20. 

PMID- 25968710
TI  - Optical trapping of silver nanoplatelets.
AB  - Optical trapping of silver nanoplatelets obtained with a simple room temperature
      chemical synthesis technique is reported. Trap spring constants are measured for
      platelets with different diameters to investigate the size-scaling behaviour.
      Experimental data are compared with models of optical forces based on the dipole
      approximation and on electromagnetic scattering within a T-matrix framework.
      Finally, we discuss applications of these nanoplatelets for surface-enhanced
      Raman spectroscopy. 

PMID- 25968711
TI  - Dissipative soliton and synchronously dual-wavelength mode-locking Yb:YSO lasers.
AB  - We experimentally demonstrate the dissipative soliton mode-locking operation of a
      Yb:YSO laser by using an all-normal dispersion cavity. Strongly chirped pulses
      are obtained with pulse duration of 9.3 ps at a repetition rate of 113.4 MHz. The
      central wavelength is 1082 nm with 3.1 nm FWHM bandwidth. A dual-wavelength
      synchronously mode-locking operation at central wavelengths of 1059.2 nm and
      1082.2 nm is also reported. Stable mode-locked pulses are achieved with pulse
      duration of 10 ps and total average output power of 164 mW. Periodic ultrashort
      beat pulses with pulse duration of 169 fs at an ultrahigh repetition rate of 1.4
      THz can be distinctly observed from the measured autocorrelation trace. To our
      knowledge, this is the first demonstration of dual-wavelength synchronously mode
      locking operation from a Yb:YSO laser. 

PMID- 25968712
TI  - Efficient optical coupling in AlGaN/GaN quantum well infrared photodetector via
      quasi-one-dimensional gold grating.
AB  - In this letter, a new kind of grating, quasi-one-dimensional gold grating, has
      been proposed to enhance the optical coupling in AlGaN/GaN quantum well infrared
      photodetector (QWIP). The electric field distribution, current density and energy
      flow are analyzed by an algorithm of finite element method (FEM). Significantly
      enhanced electric field component E(z) perpendicular to multiple quantum wells
      (MQWs) is explained by introducing the resonant coupling of surface plasmon
      polariton (SPP) and localized surface plasmon (LSP). The |E(z)|(2) in MQWs
      reaches 0.85 (V/m(2) when the electric field intensity (|E(0)|(2)) of normal
      incidence is 1 (V/m(2) at 4.65 MUm, showing 2 times and 1.3 times increase
      compared with that obtained via a one-dimensional gold grating and a two
      dimensional gold grating, respectively. The results confirm that the quasi-one
      dimensional gold grating provides more plasma excitation source and higher charge
      density with structure optimization, resulting in a high optical coupling
      efficiency of 85% in quantum well region.

PMID- 25968713
TI  - Simulation of image formation in x-ray coded aperture microscopy with
      polycapillary optics.
AB  - In x-ray coded aperture microscopy with polycapillary optics (XCAMPO), the
      microstructure of focusing polycapillary optics is used as a coded aperture and
      enables depth-resolved x-ray imaging at a resolution better than the focal spot
      dimensions. Improvements in the resolution and development of 3D encoding
      procedures require a simulation model that can predict the outcome of XCAMPO
      experiments. In this work we introduce a model of image formation in XCAMPO which
      enables calculation of XCAMPO datasets for arbitrary positions of the object
      relative to the focal plane as well as to incorporate optics imperfections. In
      the model, the exit surface of the optics is treated as a micro-structured x-ray
      source that illuminates a periodic object. This makes it possible to express the
      intensity of XCAMPO images as a convolution series and to perform simulations by
      means of fast Fourier transforms. For non-periodic objects, the model can be
      applied by enforcing artificial periodicity and setting the spatial period larger
      then the field-of-view. Simulations are verified by comparison with experimental
      data. 

PMID- 25968714
TI  - Verilog-A behavioral model for resonance-modulated silicon micro-ring modulator.
AB  - We present an accurate behavior model for Si micro-ring modulators (MRM) based on
      Verilog-A, a standard simulation tool for electronic system design. Our model
      describes the electrical characteristics of the Si MRM using an equivalent
      circuit and the optical characteristics based on the couple-mode theory. The
      accuracy of our model is confirmed by comparing simulation results of our
      behavior model with the measurement results of a fabricated Si MRM. With this
      behavior model, co-simulation of Si MRM and electronic driving circuits in the
      standard electronic design environment can be easily performed. 

PMID- 25968715
TI  - Fast phase processing in off-axis holography using multiplexing with complex
      encoding and live-cell fluctuation map calculation in real-time.
AB  - We present efficient algorithms for rapid reconstruction of quantitative phase
      maps from off-axis digital holograms. The new algorithms are aimed at speeding up
      the conventional Fourier-based algorithm. By implementing the new algorithms on a
      standard personal computer, while using only a single-core processing unit, we
      were able to reconstruct the unwrapped phase maps from one megapixel off-axis
      holograms at frame rates of up to 45 frames per second (fps). When phase
      unwrapping is not required, the same algorithms allow frame rates of up to 150
      fps for one megapixel off-axis holograms. In addition to obtaining real-time
      quantitative visualization of the sample, the increased frame rate allows
      integrating additional calculations as a part of the reconstruction process,
      providing sample-related information that was not available in real time until
      now. We use these new capabilities to extract, for the first time to our
      knowledge, the dynamic fluctuation maps of red blood cells at frame rate of 31
      fps for one megapixel holograms. 

PMID- 25968716
TI  - Femtosecond high-resolution hard X-ray spectroscopy using reflection zone plates.
AB  - An off-axis total external reflection zone plate is applied to wavelength
      dispersive X-ray spectrometry in the range from 7.8 keV to 9.0 keV. The resolving
      power E/DeltaE of up to 1.1 * 10(2), demonstrated in a synchrotron proof-of
      concept experiment, competes well with existing energy-dispersive instruments in
      this spectral range. In conjunction with the detection efficiency of (2.2 +/-
      0.6)%, providing a fairly constant count rate across the 1.2 keV band, the
      temporal pulse elongation to no more than 1.5 * 10(-15) s opens the door to wide
      range, ultra-fast hard X-ray spectroscopy at free-electron lasers (FELs).

PMID- 25968717
TI  - Hybrid III-V/silicon laser with laterally coupled Bragg grating.
AB  - In this paper, we demonstrate a compact electrically pumped distributed-feedback
      hybrid III-V/silicon laser with laterally coupled Bragg grating for the first
      time to the best of our knowledge. The hybrid laser structure consists of
      AlGaInAs/InP multi-quantum-well gain layers on top of a laterally corrugated
      silicon waveguide patterned on a silicon on insulator (SOI) substrate. A pair of
      surface couplers is integrated at the two ends of the silicon waveguide for the
      optical coupling and characterization of the ouput light. Single wavelength
      emission of ~1.55um with a side-mode-suppression- ratio larger than 20dB and low
      threshold current density of 1.54kA/cm(2) were achieved for the device under
      pulsed operation at 20  degrees C.

PMID- 25968718
TI  - Theoretical and experimental analysis of Inter-channel crosstalk between TWDM and
      fronthaul wavelengths due to stimulated Raman scattering.
AB  - In this paper, we analyze the stimulated Raman scattering (SRS) effect between
      multiple TWDM downstream wavelengths in L band and multiple fronthaul wavelength
      channels in C band theoretically, and investigate its impact on fronthaul signals
      experimentally for the first time. The impact includes two aspects, one is SRS
      induced power depletion and the other is the eye diagram distortion caused by the
      nonlinear Raman crosstalk. Experimental results show that, up to 1-dB power
      depletion would be introduced to each fronthaul wavelength channel with the
      launch power per TWDM channel varying from 8-dBm to 15-dBm. In addition, due to
      the "1" level broadening of the non-return-to-zero on-off keying (NRZ-OOK) eye
      diagram, the receiving sensitivity with 20-km standard single mode fiber (SSMF)
      transmission is decreased by ~1-dB. Therefore, a total of ~2-dB power penalty
      would be imposed on fronthaul signals when co-transmitting with TWDM downstream
      signals in the same feeder fiber. 

PMID- 25968719
TI  - Antiboding and bonding lasing modes with low gain threshold in nonlocal metallic
      nanoshell.
AB  - Based on a full-wave nonlocal Mie theory, we establish the spaser generation
      condition for compact plasmonic nanolasers in the long-wavelength limit for
      dielectric-metal core-shell nanoparticles. We found that there exist two lasing
      states arising from the hybridized antibonding and bonding modes for this coated
      nanolaser. By varying the surrounding medium and the gain materials, we can
      achieve low gain threshold for each mode with flexible radii ratios on the
      purpose of realistic easy fabrication. Numerical results show that nonlocal
      effects have different influences on the required gain threshold and gain
      refractive index of these two lasing modes, which may be of great importance in
      the design of such kind of ultrasmall nanoparticle lasers. 

PMID- 25968720
TI  - Highly-stable frequency transfer via fiber link with improved electrical error
      signal extraction and compensation scheme.
AB  - In this paper, we demonstrate a radio frequency dissemination system via fiber
      link. An electric phase-shifter is used to active compensate the phase error in
      the transfer process. Furthermore, an improved error signal extraction component
      is used to extract the phase error induced via the fiber link. The system can
      compensate large phase range fluctuation rapidly and precisely. An experiment has
      been demonstrated with this structure to disseminate a 100 MHz frequency through
      100 km. The relative frequency stability is 3 * 10(-14) at 1 s and 3 * 10(-17) at
      4000 s. It means this scheme can be used to transfer the most stable microwave
      sources through fiber link.

PMID- 25968721
TI  - Quantum control of electron wave packet during high harmonic process of H2(+) in
      a combination of a circularly polarized laser field and a Terahertz field.
AB  - By solving a two-dimensional time-dependent Schrodinger equation we investigate
      high harmonic generation (HHG) and isolated attosecond pulse generation for the
      H2+ molecular ion in a circularly polarized laser pulse combined with a Terahertz
      (THz) field. The harmonic intensity can be greatly enhanced and a continuum
      spectrum can be obtained when a THz field is added. The HHG process is studied by
      the semi-classical three-step model and the time-frequency analysis. Our studies
      show that only short trajectories contribute to HHG. Furthermore, we present the
      temporal evolution of the probability density of electron wave packet, which
      perfectly shows a clear picture of the electron's two-time recombination when a
      THz field is added, and it is the main mechanism of HHG. By superposing the
      harmonics in the range of 216-249 eV, an isolated attosecond pulse with a
      duration of about 69 attoseconds can be generated. 

PMID- 25968722
TI  - Optical cryptosystem based on phase-truncated Fresnel diffraction and transport
      of intensity equation.
AB  - A novel optical cryptosystem based on phase-truncated Fresnel diffraction (PTFD)
      and transport of intensity equation (TIE) is proposed. By using the phase
      truncation technique, a phase-encoded plaintext could be encrypted into a real
      valued noise-like intensity distribution by employing a random amplitude mask
      (RAM) and a random phase mask (RPM), which are regarded as two secret keys. For
      decryption, a generalized amplitude-phase retrieval (GAPR) algorithm combined
      with the TIE method are proposed to recover the plaintext with the help of two
      keys. Different from the current phase-truncated-based optical cryptosystems
      which need record the truncated phase as decryption keys, our scheme do not need
      the truncated phase because of the introducing of the TIE method. Moreover, the
      proposed scheme is expected to against existing attacks. A set of numerical
      simulation results show the feasibility and security of the proposed method. 

PMID- 25968723
TI  - Optical separation of heterogeneous size distributions of microparticles on
      silicon nitride strip waveguides.
AB  - We demonstrate two complementary optical separation techniques of dielectric
      particles on the surface of silicon nitride waveguides. Glass particles ranging
      from 2 MUm to 10 MUm in diameter are separated at guided powers below 40 mW. The
      effects of optical, viscous, and frictional forces on the particles are modeled
      and experimentally shown to enable separation. Particle interactions are
      investigated and shown to decrease measured particle velocity without interfering
      with the overall particle separation distribution. The demonstrated separation
      techniques have the potential to be integrated with microfluidic structures for
      cell sorting. 

PMID- 25968724
TI  - Semi-classical approach to compute RABBITT traces in multi-dimensional complex
      field distributions.
AB  - We present a semi-classical model to calculate RABBITT (Reconstruction of
      Attosecond Beating By Interference of Two-photon Transitions) traces in the
      presence of a reference infrared field with a complex two-dimensional (2D)
      spatial distribution. The evolution of the electron spectra as a function of the
      pump-probe delay is evaluated starting from the solution of the classical
      equation of motion and incorporating the quantum phase acquired by the electron
      during the interaction with the infrared field. The total response to an
      attosecond pulse train is then evaluated by a coherent sum of the contributions
      generated by each individual attosecond pulse in the train. The flexibility of
      this model makes it possible to calculate spectrograms from non-trivial 2D field
      distributions. After confirming the validity of the model in a simple 1D case, we
      extend the discussion to describe the probe-induced phase in photo-emission
      experiments on an ideal metallic surface. 

PMID- 25968725
TI  - Null reconstruction of orthogonal circular polarization hologram with large
      recording angle.
AB  - We report on the null reconstruction of polarization volume hologram recorded by
      orthogonal circularly polarized waves with a large cross angle. Based on the
      recently developed tensor theory for polarization holography, the disappearance
      of the reconstruction was analytically verified, where a nice agreement was found
      between the experimental and theoretical results. When the polarization and
      intensity hologram attain a balance, not only the null reconstruction but also
      the faithful reconstruction can be realized by the illumination of the orthogonal
      reference wave and original reference wave. As a consequence of the hologram
      recorded without paraxial approximation, the null reconstruction may lead to
      important applications, such as a potential enhancement in optical storage
      capacity for volume holograms. 

PMID- 25968726
TI  - Plasmonic absorption enhancement in periodic cross-shaped graphene arrays.
AB  - We present a wavelength tunable absorber composed of periodically patterned cross
      shaped graphene arrays in the far-infrared and THz regions. The absorption of the
      single-layer array can essentially exceed the continuous graphene sheet by
      increasing the cross-arm width, even for small graphene filling ratio. As
      chemical potential and relaxation time increase, the absorption can be
      significantly enhanced. The complementary structure shows higher absorption
      compared to the original graphene array. Moreover, the wavelength of absorption
      maximum is angle-insensitive for both TE and TM polarizations. The absorption
      efficiency can be further improved with double layers of the cross-shaped
      graphene arrays, which are helpful to design dual-band and broadband absorbers. 

PMID- 25968727
TI  - Diode-pumped continuous-wave and femtosecond Cr:LiCAF lasers with high average
      power in the near infrared, visible and near ultraviolet.
AB  - We demonstrate continuous-wave (cw), cw frequency-doubled, cw mode-locked and Q
      switched mode-locked operation of multimode diode-pumped Cr:LiCAF lasers with
      record average powers. Up to 2.54 W of cw output is obtained around 805 nm at an
      absorbed pump power of 5.5 W. Using intracavity frequency doubling with a BBO
      crystal, 0.9 W are generated around 402 nm, corresponding to an optical-to
      optical conversion efficiency of 12%. With an intracavity birefringent tuning
      plate, the fundamental and frequency-doubled laser output is tuned continuously
      in a broad wavelength range from 745 nm to 885 nm and from 375 to 440 nm,
      respectively. A saturable Bragg reflector is used to initiate and sustain mode
      locking. In the cw mode-locked regime, the Cr:LiCAF laser produces 105-fs long
      pulses near 810 nm with an average power of 0.75 W. The repetition rate is 96.4
      MHz, resulting in pulse energies of 7.7 nJ and peak powers of 65 kW. In Q
      switched mode-locked operation, pulses with energies above 150 nJ are generated. 

PMID- 25968728
TI  - Theoretical analysis and design of a near-infrared broadband absorber based on EC
      model.
AB  - We theoretically introduced a design paradigm and tool by extending the circuit
      functionalities from radio frequency to near infrared domain, and its first usage
      to design a broadband near-infrared (1.5MUm~3.5MUm) absorber, is successfully
      demonstrated. After extracting the equivalent circuit (EC) model of the absorber
      structure, the formerly relatively complicated frequency response can be
      evaluated relatively easily based on classic circuit formulas. The feasibility is
      confirmed by its consistency with the rigorous FDTD calculation. The absorber is
      an array of truncated metal-dielectric multilayer composited pyramid unit
      structure, and the gradually modified square patch design makes the absorber be
      not sensitive to the incident angle and polarization of light. 

PMID- 25968729
TI  - On the dynamics of Airy beams in nonlinear media with nonlinear losses.
AB  - We investigate on the nonlinear dynamics of Airy beams in a regime where
      nonlinear losses due to multi-photon absorption are significant. We identify the
      nonlinear Airy beam (NAB) that preserves the amplitude of the inward Hankel
      component as an attractor of the dynamics. This attractor governs also the
      dynamics of finite-power (apodized) Airy beams, irrespective of the location of
      the entrance plane in the medium with respect to the Airy waist plane. A soft
      (linear) input long before the waist, however, strongly speeds up NAB formation
      and its persistence as a quasi-stationary beam in comparison to an abrupt input
      at the Airy waist plane, and promotes the formation of a new type of highly
      dissipative, fully nonlinear Airy beam not described so far. 

PMID- 25968730
TI  - Near-infrared quarter-waveplate with near-unity polarization conversion
      efficiency based on silicon nanowire array.
AB  - Metasurfaces made of subwavelength resonators can modify the wave front of light
      within the thickness much less than free space wavelength, showing great promises
      in integrated optics. In this paper, we theoretically show that electric and
      magnetic resonances supported simultaneously by a subwavelength nanowire with
      high refractive-index can be utilized to design metasurfaces with near-unity
      transmittance. Taking silicon nanowire for instance, we design numerically a near
      infrared quarter-waveplate with high transmittance using a subwavelength nanowire
      array. The operation bandwidth of the waveplate is 0.14 MUm around the center
      wavelength of 1.71 MUm. The waveplate can convert a 45 degrees  linearly
      polarized incident light to circularly polarized light with conversion efficiency
      ranging from 94% to 98% over the operation band. The performance of quarter
      waveplate can in principle be tuned and improved through optimizing the
      parameters of nanowire arrays. Its compatibility to microelectronic technologies
      opens up a distinct possibility to integrate nanophotonics into the current
      silicon-based electronic devices. 

PMID- 25968731
TI  - Multi-functional angiographic OFDI using frequency-multiplexed dual-beam
      illumination.
AB  - Detection of blood flow inside the tissue sample can be achieved by measuring the
      local change of complex signal over time in angiographic optical coherence
      tomography (OCT). In conventional angiographic OCT, the transverse displacement
      of the imaging beam during the time interval between a pair of OCT signal
      measurements must be significantly reduced to minimize the noise due to the beam
      scanning-induced phase decorrelation at the expense of the imaging speed. Recent
      introduction of dual-beam scan method either using polarization encoding or two
      identical imaging systems in spectral-domain (SD) OCT scheme shows potential for
      high-sensitivity vasculature imaging without suffering from spurious phase noise
      caused by the beam scanning-induced spatial decorrelation. In this paper, we
      present multi-functional angiographic optical frequency domain imaging (OFDI)
      using frequency-multiplexed dual-beam illumination. This frequency multiplexing
      scheme, utilizing unique features of OFDI, provides spatially separated dual
      imaging beams occupying distinct electrical frequency bands that can be
      demultiplexed in the frequency domain processing. We demonstrate the 3D multi
      functional imaging of the normal mouse skin in the dorsal skin fold chamber
      visualizing distinct layer structures from the intensity imaging, information
      about mechanical integrity from the polarization-sensitive imaging, and depth
      resolved microvasculature from the angiographic imaging that are simultaneously
      acquired and automatically co-registered. 

PMID- 25968732
TI  - Phase-space properties of magneto-optical traps utilising micro-fabricated
      gratings.
AB  - We have used diffraction gratings to simplify the fabrication, and dramatically
      increase the atomic collection efficiency, of magneto-optical traps using micro
      fabricated optics. The atom number enhancement was mainly due to the increased
      beam capture volume, afforded by the large area (4cm(2)) shallow etch (~ 200nm)
      binary grating chips. Here we provide a detailed theoretical and experimental
      investigation of the on-chip magneto-optical trap temperature and density in four
      different chip geometries using (87)Rb, whilst studying effects due to MOT
      radiation pressure imbalance. With optimal initial MOTs on two of the chips we
      obtain both large atom number (2*10(7)) and sub-Doppler temperatures (50 MUK)
      after optical molasses.

PMID- 25968733
TI  - Quantitative analysis of light scattering in polarization-resolved nonlinear
      microscopy.
AB  - Polarization resolved nonlinear microscopy (PRNM) is a powerful technique to gain
      microscopic structural information in biological media. However, deep imaging in
      a variety of biological specimens is hindered by light scattering phenomena,
      which not only degrades the image quality but also affects the polarization state
      purity. In order to quantify this phenomenon and give a framework for
      polarization resolved microscopy in thick scattering tissues, we develop a
      characterization methodology based on four wave mixing (FWM) process. More
      specifically, we take advantage of two unique features of FWM, meaning its
      ability to produce an intrinsic in-depth local coherent source and its capacity
      to quantify the presence of light depolarization in isotropic regions inside a
      sample. By exploring diverse experimental layouts in phantoms with different
      scattering properties, we study systematically the influence of scattering on the
      nonlinear excitation and emission processes. The results show that depolarization
      mechanisms for the nonlinearly generated photons are highly dependent on the
      scattering center size, the geometry used (epi/forward) and, most importantly, on
      the thickness of the sample. We show that the use of an un-analyzed detection
      makes the polarization-dependence read-out highly robust to scattering effects,
      even in regimes where imaging might be degraded. The effects are illustrated in
      polarization resolved imaging of myelin lipid organization in mouse spinal cords.

PMID- 25968734
TI  - Automated choroid segmentation based on gradual intensity distance in HD-OCT
      images.
AB  - The choroid is an important structure of the eye and plays a vital role in the
      pathology of retinal diseases. This paper presents an automated choroid
      segmentation method for high-definition optical coherence tomography (HD-OCT)
      images, including Bruch's membrane (BM) segmentation and choroidal-scleral
      interface (CSI) segmentation. An improved retinal nerve fiber layer (RNFL)
      complex removal algorithm is presented to segment BM by considering the structure
      characteristics of retinal layers. By analyzing the characteristics of CSI
      boundaries, we present a novel algorithm to generate a gradual intensity distance
      image. Then an improved 2-D graph search method with curve smooth constraints is
      used to obtain the CSI segmentation. Experimental results with 212 HD-OCT images
      from 110 eyes in 66 patients demonstrate that the proposed method can achieve
      high segmentation accuracy. The mean choroid thickness difference and overlap
      ratio between our proposed method and outlines drawn by experts was 6.72um and
      85.04%, respectively. 

PMID- 25968735
TI  - Double-layered metal grating for high-performance refractive index sensing.
AB  - The detection of minuscule changes in the local refractive index by localized
      surface plasmon resonances (LSPRs), carried by metal nanostructures, has been
      used successfully in applications such as real-time and label-free detection of
      molecular binding events. However, localized plasmons demonstrate 1-2 orders of
      magnitude lower figure of merit (FOM) compared with their propagating
      counterparts. Here, we propose and experimentally demonstrate a high-performance
      refractive index sensor based on a structure of double-layered metal grating
      (DMG) with an FOM and FOM* reaching 38 and 40 respectively under normal
      incidence. Such a high FOM and FOM* arise from a result of a sharp fano
      resonance, which is caused by the coherent interference between the LSPR from the
      individual top gold stripes and Wood's anomaly (WA). Moreover, a small conformal
      decay length of ~68 nm is determined in DMG, indicating that the DMG is a
      promising candidate for label-free biomedical sensing. 

PMID- 25968736
TI  - Reflectionless compact plasmonic waveguide mode converter by using a mode
      selective cavity.
AB  - A compact transmissive plasmonic waveguide mode converter which aims for the
      elimination of reflection and transmission of unconverted mode is proposed. The
      proposed scheme exploits a cavity formed by mode selective mirrors, which only
      allows two output modes: the transmission of the target mode and the reflection
      of the input mode. By appropriately tuning cavity lengths, the reflection of the
      input mode can also be suppressed to near zero by destructive interference,
      thereby all the residual outgoing modes are suppressed. The proposed device might
      be useful in the design of integrated photonic system since it relaxes the
      problem of unwanted reflection. 

PMID- 25968737
TI  - Hyperspectral image reconstruction for x-ray fluorescence tomography.
AB  - A penalized maximum-likelihood estimation is proposed to perform hyperspectral
      (spatio-spectral) image reconstruction for X-ray fluorescence tomography. The
      approach minimizes a Poisson-based negative log-likelihood of the observed photon
      counts, and uses a penalty term that has the effect of encouraging local
      continuity of model parameter estimates in both spatial and spectral dimensions
      simultaneously. The performance of the reconstruction method is demonstrated with
      experimental data acquired from a seed of arabidopsis thaliana collected at the
      13-ID-E microprobe beamline at the Advanced Photon Source. The resulting element
      distribution estimates with the proposed approach show significantly better
      reconstruction quality than the conventional analytical inversion approaches, and
      allows for a high data compression factor which can reduce data acquisition times
      remarkably. In particular, this technique provides the capability to
      tomographically reconstruct full energy dispersive spectra without compromising
      reconstruction artifacts that impact the interpretation of results. 

PMID- 25968738
TI  - Single-end simultaneous temperature and strain sensing techniques based on
      Brillouin optical time domain reflectometry in few-mode fibers.
AB  - Recently there is a growing interest in developing few-mode fiber (FMF) based
      distributed sensors, which can attain higher spatial resolution and sensitivity
      compared with the conventional single-mode approaches. However, current
      techniques require two lightwaves injected into both ends of FMF, resulting in
      their complicated setup and high cost, which causes a big issue for geotechnical
      and petroleum applications. In this paper, we present a single-end FMF-based
      distributed sensing system that allows simultaneous temperature and strain
      measurement by Brillouin optical time-domain reflectometry (BOTDR) and heterodyne
      detection. Theoretical analysis and experimental assessment of multi-parameter
      discriminative measurement techniques applied to distributed FMF sensors are
      presented. Experimental results confirm that FM-BOTDR has similar performance
      with two-end methods such as FM-BOTDA, but with simpler setup and lower cost. The
      temperature-induced expansion strain (TIES) in response to different modes is
      discussed as well. Furthermore, we optimized the FMF design by exploiting modal
      profile and doping concentration, which indicates up to fivefold enhancement in
      measurement accuracy. This novel distributed FM-sensing system endows with good
      sensitivity characteristics and can prevent catastrophic failure in many
      applications. 

PMID- 25968739
TI  - Double-clad fiber coupler for partially coherent detection.
AB  - Double-clad fibers (DCF) have many advantages in fibered confocal microscopes as
      they allow for coherent illumination through their core and partially coherent
      detection through their inner cladding. We report a double-clad fiber coupler
      (DCFC) made from small inner cladding DCF that preserves optical sectioning in
      confocal microscopy while increasing collection efficiency and reducing coherent
      effects. Due to the small inner cladding, previously demonstrated fabrication
      methods could not be translated to this coupler's fabrication. To make such a
      coupler possible, we introduce in this article three new design concepts. The
      resulting DCFC fabricated using two custom fibers and a modified fusion-tapering
      technique achieves high multimodal extraction (>=70 %) and high single mode
      transmission (>=80 %). Its application to reflectance confocal microscopy showed
      a 30-fold increase in detected signal intensity, a 4-fold speckle contrast
      reduction with a penalty in axial resolution of a factor 2. This coupler paves
      the way towards more efficient confocal microscopes for clinical applications. 

PMID- 25968740
TI  - Laser straightness interferometer system with rotational error compensation and
      simultaneous measurement of six degrees of freedom error parameters.
AB  - A laser straightness interferometer system with rotational error compensation and
      simultaneous measurement of six degrees of freedom error parameters is proposed.
      The optical configuration of the proposed system is designed and the mathematic
      model for simultaneously measuring six degrees of freedom parameters of the
      measured object including three rotational parameters of the yaw, pitch and roll
      errors and three linear parameters of the horizontal straightness error, vertical
      straightness error and straightness error's position is established. To address
      the influence of the rotational errors produced by the measuring reflector in
      laser straightness interferometer, the compensation method of the straightness
      error and its position is presented. An experimental setup was constructed and a
      series of experiments including separate comparison measurement of every
      parameter, compensation of straightness error and its position and simultaneous
      measurement of six degrees of freedom parameters of a precision linear stage were
      performed to demonstrate the feasibility of the proposed system. Experimental
      results show that the measurement data of the multiple degrees of freedom
      parameters obtained from the proposed system are in accordance with those
      obtained from the compared instruments and the presented compensation method can
      achieve good effect in eliminating the influence of rotational errors on the
      measurement of straightness error and its position. 

PMID- 25968741
TI  - Anisotropic metamaterial optical fibers.
AB  - Internal physical structure can drastically modify the properties of waveguides:
      photonic crystal fibers are able to confine light inside a hollow air core by
      Bragg scattering from a periodic array of holes, while metamaterial loaded
      waveguides for microwaves can support propagation at frequencies well below
      cutoff. Anisotropic metamaterials assembled into cylindrically symmetric
      geometries constitute light-guiding structures that support new kinds of exotic
      modes. A microtube of anodized nanoporous alumina, with nanopores radially
      emanating from the inner wall to the outer surface, is a manifestation of such an
      anisotropic metamaterial optical fiber. The nanopores, when filled with a
      plasmonic metal such as silver or gold, greatly increase the electromagnetic
      anisotropy. The modal solutions in such anisotropic circular waveguides can be
      uncommon Bessel functions with imaginary orders. 

PMID- 25968742
TI  - Ultra-high-extinction-ratio 2 * 2 silicon optical switch with variable splitter.
AB  - We demonstrate a record-high extinction-ratio of 50.4 dB in a 2 * 2 silicon Mach
      Zehnder switch equipped with a variable splitter as the front 3-dB splitter. The
      variable splitter is adjusted to compensate for the splitting-ratio mismatch
      between the front and rear 3-dB splitters. The high extinction ratio does not
      rely on waveguide crossings and meets a strong demand in applications to
      multiport circuit switches. Large fabrication tolerance will make the high
      extinction ratio compatible with a volume production with standard complementary
      metal-oxide semiconductor fabrication facilities. 

PMID- 25968743
TI  - Fabrication of bowtie aperture antennas for producing sub-20 nm optical spots.
AB  - Bowtie aperture antennas are known to generate sub-diffraction limited optical
      spots in the visible and near-infrared frequencies, which can be applied to many
      areas. Regular bowtie apertures fabricated by FIB suffer from tapered sidewall
      and rounded corner, which degrade its optical enhancement and localization. In
      this work, a new fabrication method is demonstrated to manufacture bowtie
      aperture antennas which can produce optical spots with lateral size smaller than
      20 nm. We also employ numerical simulations to compute the near-field
      distribution on the surface of the bowtie aperture with topography extracted from
      the fabrication antennas. The near-field distribution measured by s-NSOM agrees
      well with the simulation and confirms the improved near-field localization of our
      bowtie aperture. This new fabrication method can be applied to other types of
      ridged apertures, which promises wide applications of deep sub-diffraction
      limited optical spots in many areas. 

PMID- 25968744
TI  - Efficient interfacing photonic and long-range dielectric-loaded plasmonic
      waveguides.
AB  - Long-range dielectric-loaded surface plasmon-polariton waveguides (LR-DLSPPWs)
      operating at telecom wavelengths are efficiently (end-fire) interfaced with
      photonic waveguides by taking advantage of very similar lateral mode field
      profiles in these waveguide configurations. The LR-DLSPPWs are formed by 1-MUm
      high and 1-MUm-wide polymer ridges fabricated atop 15-nm-thin and 500-nm-wide
      gold stripes supported by a 289-nm-thick ormoclear polymer deposited on a low
      index (1.34) layer of cytop, whereas gold stripes are absent in the photonic
      waveguide configuration that is identical to the plasmonic one in all other
      respects. The coupling efficiency between LR-DLSPPWs and photonic waveguides is
      numerically estimated to be 97%, decreasing by only a few percents for non
      centered gold stripes (as long as a gold stripe is kept inside the polymer
      ridge). The fabricated LR-DLSPPWs coupled to photonic waveguides are first
      characterized using amplitude- and phase-resolved near-field imaging of
      propagating radiation that reveals very similar mode field distributions in these
      waveguides as well as their efficient interfacing. The coupling efficiency is
      then experimentally characterized using the cutback approach resulting in an
      average level of 75% per interface, while the LR-DLSPPW mode propagation length
      is estimated to be on average 0.3 mm. Possible reasons for differences between
      experimental and simulation results are discussed, indicating that a 3-nm-thin
      titanium layer (used for improving adhesion between gold and ormoclear)
      introduces substantial mode absorption. The results obtained open new
      perspectives for realization of hybrid photonic-plasmonic components and
      circuits. 

PMID- 25968745
TI  - Delivery of focused short pulses through a multimode fiber.
AB  - Light propagation through multimode fibers suffers from spatial distortions that
      lead to a scrambled intensity profile. In previous work, the correction of such
      distortions using various wavefront control methods has been demonstrated in the
      continuous wave case. However, in the ultra-fast pulse regime, modal dispersion
      temporally broadens a pulse after propagation. Here, we present a method that
      compensates for spatial distortions and mitigates temporal broadening due to
      modal dispersion by a selective phase conjugation process in which only modes of
      similar group velocities are excited. The selectively excited modes are forced to
      follow certain paths through the multimode fiber and interfere constructively at
      the distal tip to form a focused spot with minimal temporal broadening. We
      demonstrate the delivery of focused 500 fs pulses through a 30 cm long step-index
      multimode fiber. The achieved pulse duration corresponds to approximately 1/30th
      of the duration obtained if modal dispersion was not controlled. Moreover, we
      measured a detailed two-dimensional map of the pulse duration at the output of
      the fiber and confirmed that the focused spot produces a two-photon absorption
      effect. This work opens new possibilities for ultra-thin multiphoton imaging
      through multimode fibers. 

PMID- 25968746
TI  - Absolute positioning by multi-wavelength interferometry referenced to the
      frequency comb of a femtosecond laser.
AB  - A multi-wavelength interferometer utilizing the frequency comb of a femtosecond
      laser as the wavelength ruler is tested for its capability of ultra-precision
      positioning for machine axis control. The interferometer uses four different
      wavelengths phase-locked to the frequency comb and then determines the absolute
      position through a multi-channel scheme of detecting interference phases in
      parallel so as to enable fast, precise and stable measurements continuously over
      a few meters of axis-travel. Test results show that the proposed interferometer
      proves itself as a potential candidate of absolute-type position transducer
      needed for next-generation ultra-precision machine axis control, demonstrating
      linear errors of less than 61.9 nm in peak-to-valley over a 1-meter travel with
      an update rate of 100 Hz when compared to an incremental-type He-Ne laser
      interferometer. 

PMID- 25968747
TI  - Intravascular confocal photoacoustic endoscope with dual-element ultrasonic
      transducer.
AB  - We have developed an intravascular confocal photoacoustic (PA) endoscope with
      symmetrically aligned dual-element ultrasonic transducers. By combining focused
      laser excitation and focused acoustic collection, the intravascular confocal PA
      endoscope is capable of realizing resolution enhanced intravascular PA imaging
      with improved signal-to-noise ratio (SNR) to ameliorate the resolution reduction
      caused by laser scattering with increasing tissue depth. The detection
      sensitivity of the endoscope is improved by 5 dB compared with that of single
      transducer endoscope, and the transverse resolution of the system can up to 13
      MUm. Intravascular PA tomography of a normal vessel and an atherosclerotic vessel
      have been performed to demonstrate the imaging ability of the system. This
      intravascular confocal PA endoscope with an outer diameter of 1.2 mm supports
      potential for clinical applications in intravascular plaque imaging and
      subsequent diagnosis. 

PMID- 25968748
TI  - Effects of non-Kolmogorov turbulence on the spiral spectrum of Hypergeometric
      Gaussian laser beams.
AB  - We study the effects of non-Kolmogorov turbulence on the orbital angular momentum
      (OAM) of Hypergeometric-Gaussian (HyGG) beams in a paraxial atmospheric link. The
      received power and crosstalk power of OAM states of the HyGG beams are
      established. It is found that the hollowness parameter of the HyGG beams plays an
      important role in the received power and crosstalk power. The larger values of
      hollowness parameter give rise to the higher received power and lower crosstalk
      power. The results also show that the smaller OAM quantum number and longer
      wavelength of the launch beam may lead to the higher received power and lower
      crosstalk power. 

PMID- 25968749
TI  - Extending mode areas of single-mode all-solid photonic bandgap fibers.
AB  - Mode area scaling of optical fiber is highly desirable for high power fiber laser
      applications. It is well known that incorporation of additional smaller cores in
      the cladding can be used to resonantly out-couple higher-order modes from a main
      core to suppress higher-order-mode propagation in the main core. Using a novel
      design with multiple coupled smaller cores in the cladding, we have successfully
      demonstrated a single-mode photonic bandgap fiber with record effective mode area
      of ~2650um(2). Detailed numeric studies have been conducted for multiple cladding
      designs. For the optimal designs, the simulated minimum higher-order-mode losses
      are well over two orders of magnitudes higher than that of fundamental mode when
      expressed in dBs. To our knowledge, this is the best higher-order-mode
      suppression ever found in fibers with this large effective mode areas. We have
      also experimentally validated one of the designs. M(2)<1.08 across the
      transmission band was demonstrated.

PMID- 25968750
TI  - Using linear polarization for sensing and sizing dielectric nanoparticles.
AB  - The spectral evolution of the degree of linear polarization (PL) at a scattering
      angle of 90 degrees  is studied numerically for high refractive index (HRI)
      dielectric spherical nanoparticles. The behaviour of PL(90 degrees ) is analysed
      as a function of the refractive index of the surrounding medium and the particle
      radius, and it is compared with the more conventional extinction efficiency
      parameter (Qext), usually used for sensing applications. We focus on the spectral
      region where both electric and magnetic resonances of order not higher than two
      are located for various semiconductor materials with low absorption. Although
      both Qext and PL(90 degrees ) are identifiers of the refractive index of the
      surrounding medium, the spectral of PL(90 degrees ) has only a small, linear
      dependence on nanoparticle size R. This weak dependence makes it experimentally
      feasible to perform real-time retrievals of both the refractive index of the
      external medium and the NP size R. 

PMID- 25968751
TI  - Surface plasmon hurdles leading to a strongly localized giant field enhancement
      on two-dimensional (2D) metallic diffraction gratings.
AB  - An extensive numerical study of diffraction of a plane monochromatic wave by a
      single gold cone on a plane gold substrate and by a periodical array of such
      cones shows formation of curls in the map of the Poynting vector. They result
      from the interference between the incident wave, the wave reflected by the
      substrate, and the field scattered by the cone(s). In case of a single cone, when
      going away from its base along the surface, the main contribution in the
      scattered field is given by the plasmon surface wave (PSW) excited on the
      surface. As expected, it has a predominant direction of propagation, determined
      by the incident wave polarization. Two particular cones with height approximately
      1/6 and 1/3 of the wavelength are studied in detail, as they present the
      strongest absorption and field enhancement when arranged in a periodic array.
      While the PSW excited by the smaller single cone shows an energy flux globally
      directed along the substrate surface, we show that curls of the Poynting vector
      generated with the larger cone touch the diopter surface. At this point, their
      direction is opposite to the energy flow of the PSW, which is then forced to jump
      over the vortex regions. Arranging the cones in a two-dimensional subwavelength
      periodic array (diffraction grating), supporting a specular reflected order only,
      resonantly strengthens the field intensity at the tip of cones and leads to a
      field intensity enhancement of the order of 10 000 with respect to the incident
      wave intensity. The enhanced field is strongly localized on the rounded top of
      the cones. It is accompanied by a total absorption of the incident light
      exhibiting large angular tolerances. This strongly localized giant field
      enhancement can be of much interest in many applications, including fluorescence
      spectroscopy, label-free biosensing, surface-enhanced Raman scattering (SERS),
      nonlinear optical effects and photovoltaics. 

PMID- 25968752
TI  - On achievable rates for long-haul fiber-optic communications.
AB  - Lower bounds on mutual information (MI) of long-haul optical fiber systems for
      hard-decision and soft-decision decoding are studied. Ready-to-use expressions to
      calculate the MI are presented. Extensive numerical simulations are used to
      quantify how changes in the optical transmitter, receiver, and channel affect the
      achievable transmission rates of the system. Special emphasis is put to the use
      of different quadrature amplitude modulation formats, channel spacings, digital
      back-propagation schemes and probabilistic shaping. The advantages of using MI
      over the prevailing Q-factor as a figure of merit of coded optical systems are
      also highlighted. 

PMID- 25968753
TI  - On the performance of label-free biosensors based on vertical one-dimensional
      photonic crystal resonant cavities.
AB  - In this work three Fabry-Perot (FP) resonant cavities based on vertical
      silicon/air one-dimensional photonic crystals (1DPhCs) featuring different
      architectures and fluidic functionalities are designed, and the role of key
      design parameters on their ideal biosensing performance, i.e. surface
      sensitivity, limit of detection, range of linearity, is investigated. Numerical
      calculations of the transmission spectra of the 1DPhC FP resonant cavities using
      the Transfer Matrix Method (TMM), versus thickness of a biolayer simulating
      biomolecules (e.g. proteins) adsorbed on the 1DPhC FP cavity surfaces, show that
      biosensors with surface sensitivity up to 300 pm/nm, limit of detection down to
      0.07 nm, and high linearity over the range 0-50 nm of biolayer thickness can be
      achieved. 

PMID- 25968754
TI  - Interferometric control of absorption in thin plasmonic metamaterials: general
      two port theory and broadband operation.
AB  - In order to extend the Coherent Perfect Absorption (CPA) phenomenology to
      broadband operation, the interferometric control of absorption is investigated in
      two-port systems without port permutation symmetry. Starting from the two-port
      theory of CPA treated within the Scattering Matrix formalism, we demonstrate that
      for all linear two-port systems with reciprocity the absorption is represented by
      an ellipse as function of the relative phase and intensity of the two input
      beams, and it is uniquely determined by the device single-beam reflectance and
      transmittance, and by the dephasing of the output beams. The basic properties of
      the phenomenon in systems without port permutation symmetry show that CPA
      conditions can still be found in such asymmetric devices, while the asymmetry can
      be beneficial for broadband operation. As experimental proof, we performed
      transmission measurements on a metal-semiconductor metamaterial, employing a Mach
      Zehnder interferometer. The experimental results clearly evidence the elliptical
      feature of absorption and trace a route towards broadband operation. 

PMID- 25968755
TI  - Ultrafast optical switching using photonic molecules in photonic crystal
      waveguides.
AB  - We study the coupling between photonic molecules and waveguides in photonic
      crystal slab structures using finite-difference time-domain method and coupled
      mode theory. In a photonic molecule with two cavities, the coupling of cavity
      modes results in two super-modes with symmetric and anti-symmetric field
      distributions. When two super-modes are excited simultaneously, the energy of
      electric field oscillates between the two cavities. To excite and probe the
      energy oscillation, we integrate photonic molecule with two photonic crystal
      waveguides. In coupled structure, we find that the quality factors of two super
      modes might be different because of different field distributions of super-modes.
      After optimizing the radii of air holes between two cavities of photonic
      molecule, nearly equal quality factors of two super-modes are achieved, and
      coupling strengths between the waveguide modes and two super-modes are almost the
      same. In this case, complete energy oscillations between two cavities can be
      obtained with a pumping source in one waveguide, which can be read out by another
      waveguide. Finally, we demonstrate that the designed structure can be used for
      ultrafast optical switching with a time scale of a few picoseconds. 

PMID- 25968756
TI  - A full-duplex CATV/wireless-over-fiber lightwave transmission system.
AB  - A full-duplex CATV/wireless-over-fiber lightwave transmission system consisting
      of one broadband light source (BLS), two optical interleavers (ILs), one
      intensity modulator, and one phase modulator is proposed and experimentally
      demonstrated. The downstream light is optically promoted from 10Gbps/25GHz
      microwave (MW) data signal to 10Gbps/100GHz and 10Gbps/50GHz millimeter-wave
      (MMW) data signals in fiber-wireless convergence, and intensity-modulated with 50
      550 MHz CATV signal. For up-link transmission, the downstream light is phase
      remodulated with 10Gbps/25GHz MW data signal in fiber-wireless convergence. Over
      a 40-km single-mode fiber (SMF) and a 10-m radio frequency (RF) wireless
      transport, bit error rate (BER), carrier-to-noise ratio (CNR), composite second
      order (CSO), and composite triple-beat (CTB) are observed to perform well in such
      full-duplex CATV/wireless-over-fiber lightwave transmission systems. This full
      duplex 100-GHz/50-GHz/25-GHz/550-MHz lightwave transmission system is an
      attractive alternative. This transmission system not only presents its
      advancement in the integration of fiber backbone and CATV/wireless feeder
      networks, but also it provides the advantages of a communication channel for
      higher data rates and bandwidth. 

PMID- 25968757
TI  - Effects of unresolvable edges in grating-based X-ray differential phase imaging.
AB  - We investigated effects of unresolvable sharp edges on images obtained in a
      grating-based X-ray differential phase imaging technique. Results of numerical
      calculations for monochromatic X-rays show that an unresolvable sharp edge
      generates not only differential-phase contrast but also visibility contrast. The
      latter shows that the visibility contrast has another major origin other than
      ultra-small-angle X-ray scattering (USAXS) from randomly distributed unresolvable
      microstructures, which has been considered the main origin for the contrast. The
      effects were experimentally confirmed using a synchrotron X-ray source. 

PMID- 25968759
TI  - Wideband multilayer mirrors with minimal layer thicknesses variation.
AB  - Wideband multilayers designed for various applications in hard X-ray to Extreme
      UV spectral regions are based on a layered system with layer thicknesses varying
      largely in depth. However, because the internal structure of a thin film depends
      on its thickness, this will result in multilayers in which material properties
      such as density, crystallinity, dielectric constant and effective thickness vary
      from layer to layer. This variation causes the fabricated multilayers to deviate
      from the model and negatively influences the reflectivity of the multilayers. In
      this work we solve this problem by developing designs of wideband multilayers
      with strongly reduced layer thickness variations in depth, without essential
      degradation of their optical characteristics. 

PMID- 25968758
TI  - Stereoscopic 3D display technique using spatiotemporal interlacing has improved
      spatial and temporal properties.
AB  - Stereoscopic 3D (S3D) displays use spatial or temporal interlacing to send
      different images to the two eyes. Temporal interlacing delivers images to the
      left and right eyes alternately in time; it has high effective spatial resolution
      but is prone to temporal artifacts. Spatial interlacing delivers even pixel rows
      to one eye and odd rows to the other eye simultaneously; it is subject to spatial
      limitations such as reduced spatial resolution. We propose a spatiotemporal
      interlacing protocol that interlaces the left- and right-eye views spatially, but
      with the rows being delivered to each eye alternating with each frame. We
      performed psychophysical experiments and found that flicker, motion artifacts,
      and depth distortion are substantially reduced relative to the temporal
      interlacing protocol, and spatial resolution is better than in the spatial
      interlacing protocol. Thus, the spatiotemporal-interlacing protocol retains the
      benefits of spatial and temporal interlacing while minimizing or even eliminating
      the drawbacks. 

PMID- 25968760
TI  - One-step hyperentanglement purification and hyperdistillation with linear optics.
AB  - We investigate a new approach for achieving hyperdistillation and
      hyperentanglement purification operations simultaneously on two-photon systems,
      whose state is described by nonlocal hyperentangled Bell states on both the
      spatial mode and polarization degree of freedoms. Exploiting linear optics and
      local entanglement resource, the quantum nondemolition (QND) parity-checking
      measurement and the heralded two-qubit amplification could are key steps in our
      scheme. With the QND parity-checking measurement and heralded qubit amplification
      operations, both the bit-flip (phase-flip) errors caused by decoherence in noisy
      channels and the vacuum errors caused by the transmission losses can be
      corrected. We show that the proposed scheme provides a new solution to overcome
      the problem of photon losses and decoherence simultaneously, which could be
      achieved with current technologies. 

PMID- 25968761
TI  - Chirped pulse heterodyne for optimal beat note detection between a frequency comb
      and a continuous wave laser.
AB  - Chirped pulse heterodyne is proposed to maximize the signal-to-noise ratio (SNR)
      when measuring the beat note between an optical frequency comb and a continuous
      wave (CW) laser. The noise model reveals that all the comb power within the
      largest possible detection bandwidth can be used to increase the SNR. The chirped
      comb/CW interference experiment is shown to be equivalent to CW/CW interference,
      using the comb's spectrally available power. The approach can also greatly
      alleviate dynamic range issues when detected pulsed heterodyne signals. A beat
      note SNR of 68.3 dB in a 100 kHz bandwidth is achieved. 

PMID- 25968762
TI  - Theoretical, numerical and experimental study of geometrical parameters that
      affect anisotropy measurements in polarization-resolved SHG microscopy.
AB  - Polarization-resolved second harmonic generation (P-SHG) microscopy is an
      efficient imaging modality for in situ observation of biopolymers structure in
      tissues, providing information about their mean in-plane orientation and their
      molecular structure and 3D distribution. Nevertheless, P-SHG signal build-up in a
      strongly focused regime is not throroughly understood yet, preventing reliable
      and reproducible measurements. In this study, theoretical analysis, vectorial
      numerical simulations and experiments are performed to understand how geometrical
      parameters, such as excitation and collection numerical apertures and detection
      direction, affect P-SHG imaging in homogeneous collagen tissues. A good agreement
      is obtained in tendon and cornea, showing that detection geometry significantly
      affects the SHG anisotropy measurements, but not the measurements of collagen in
      plane orientation. 

PMID- 25968763
TI  - Heterogeneous integration of gallium nitride light-emitting diodes on diamond and
      silica by transfer printing.
AB  - We report the transfer printing of blue-emitting micron-scale light-emitting
      diodes (micro-LEDs) onto fused silica and diamond substrates without the use of
      intermediary adhesion layers. A consistent Van der Waals bond was achieved via
      liquid capillary action, despite curvature of the LED membranes following release
      from their native silicon growth substrates. The excellence of diamond as a heat
      spreader allowed the printed membrane LEDs to achieve optical power output
      density of 10 W/cm(2) when operated at a current density of 254 A/cm(2). This
      high-current-density operation enabled optical data transmission from the LEDs at
      400 Mbit/s.

PMID- 25968764
TI  - All-polarization maintaining, graphene-based femtosecond Tm-doped all-fiber
      laser.
AB  - We report an all-fiber, all-polarization maintaining (PM) ultrafast Tm-doped
      fiber laser mode-locked by a multilayer graphene-based saturable absorber (SA).
      The laser emits 603 fs-short pulses centered at 1876 nm wavelength with 6.6 nm of
      bandwidth and 41 MHz repetition rate. Graphene used as saturable absorber was
      obtained via chemical vapor deposition (CVD) on copper substrate and immersed in
      a poly(methylmethacrylate) (PMMA) support, forming a stable, free-standing foil
      containing 12 graphene layers, suitable for the use in a fiber laser. The
      generated 603 fs pulses are the shortest reported pulses achieved from a Tm-doped
      laser mode-locked by graphene saturable absorber so far. Additionally, this is
      the first demonstration of an all-PM Tm-doped fiber laser incorporating a
      graphene-based SA. Such cost-effective, compact and stable fiber lasers might be
      considered as sources usable in nonlinear frequency conversion, mid-infrared
      spectroscopy and remote sensing. 

PMID- 25968765
TI  - Analysis of PT-symmetric volume gratings beyond the paraxial approximation.
AB  - We study the diffraction produced by a PT -symmetric volume Bragg grating that
      combines modulation of refractive index and gain/loss of the same periodicity
      with a quarter-period shift between them. Such a complex grating has a
      directional coupling between the different diffraction orders, which allows us to
      find an analytic solution for the first three orders of the full Maxwell
      equations without resorting to the paraxial approximation. This is important,
      because only with the full equations can the boundary conditions, allowing for
      reflections, be properly implemented. Using our solution we analyze the
      properties of such a grating in a wide variety of configurations. 

PMID- 25968766
TI  - Simultaneous measurements of electrophoretic and dielectrophoretic forces using
      optical tweezers.
AB  - Herein, charged microbeads handled with optical tweezers are used as a sensitive
      probe for simultaneous measurements of electrophoretic and dielectrophoretic
      forces. We first determine the electric charge carried by a single bead by
      keeping it in a predictable uniform electric field produced by two parallel
      planar electrodes, then, we examine same bead's response in proximity to a tip
      electrode. In this case, besides electric forces, the bead simultaneously
      experiences non-negligible dielectrophoretic forces produced by the strong
      electric field gradient. The stochastic and deterministic motions of the trapped
      bead are theoretically and experimentally analysed in terms of the
      autocorrelation function. By fitting the experimental data, we are able to
      extract simultaneously the spatial distribution of electrophoretic and
      dielectrophoretic forces around the tip. Our approach can be used for determining
      actual, total force components in the presence of high-curvature electrodes or
      metal scanning probe tips. 

PMID- 25968767
TI  - Silicon photonics integrated circuits: a manufacturing platform for high density,
      low power optical I/O's.
AB  - Silicon photonics integrated circuits are considered to enable future computing
      systems with optical input-outputs co-packaged with CMOS chips to circumvent the
      limitations of electrical interfaces. In this paper we present the recent
      progress made to enable dense multiplexing by exploiting the integration
      advantage of silicon photonics integrated circuits. We also discuss the
      manufacturability of such circuits, a key factor for a wide adoption of this
      technology. 

PMID- 25968768
TI  - Influence of pump bandwidth on the efficiency of side-pumped, double-beam mode
      controlled lasers: establishing a new record for Nd:YLiF(4) lasers using VBG.
AB  - We analyze the performance of a VBG equipped diode of narrow linewidth in a side
      pumped double-beam, mode-controlled resonator and demonstrate power scaling
      without loss of beam quality by a factor of three, when compared to previous
      results. 69 W of diffraction-limited laser output power at 1053 nm in a Nd:YLF
      lasers are demonstrated with slope efficiency of 65% and record optical-to
      optical efficiency of 60%. 

PMID- 25968769
TI  - Self-propelling bacteria mimic coherent light decorrelation.
AB  - We show here that live e-coli bacterial culture, thanks to the self-propelling
      feature, can significantly reduce the coherent noise. In fact, the typical self
      propelled drive of such microorganisms provides enough time diversity in speckle
      patterns. Optical properties of a bacteria suspension have been investigated and
      analyzed thus showing that it behaves as a quite good optical speckle
      decorrelation device. Samples with different bacteria densities have been
      studied. The decorrelation effect has been demonstrated by probing the imaging
      performance in through transmission in coherent microscope configuration. 

PMID- 25968770
TI  - A classification sensor based on compressed optical Radon transform.
AB  - We present a thin-film sensor that optically measures the Radon transform of an
      image focussed onto it. Measuring and classifying directly in Radon space, rather
      than in image space, is fast and yields robust and high classification rates. We
      explain how the number of integral measurements required for a given
      classification task can be reduced by several orders of magnitude. Our
      experiments achieve classification rates of 98%-99% for complex hand gesture and
      motion detection tasks with as few as 10 photosensors. Our findings have the
      potential to stimulate further research towards a new generation of application
      oriented classification sensors for use in areas such as biometry, security,
      diagnostics, surface inspection, and human-computer interfaces. 

PMID- 25968771
TI  - Differential twin receiving fiber-optic magnetic field and electric current
      sensor utilizing a microfiber coupler.
AB  - A magnetic field and electric current meter is proposed based on a differential
      twin receiving microfiber coupler (MC) sensor. The sensor is fabricated by
      bonding a MC and an aluminium (Al) wire together. With the small diameter of
      several micrometers, the output power at each port of the coupler shows high
      sensitivity to the distortion of Al wire from the Lorentz force induced by the
      magnetic field or the thermal expansion caused by the electric current. The ratio
      of the difference to the sum of the output signals from the two output ports can
      be used to eliminate the variation in the sensitivity. Using our proposed sensor,
      we measured a magnetic field sensitivity of ~0.0496 mT(-1), current sensitivity
      of ~1.0899 A(-1) without any magnetic field, and good repeatability are also
      shown in this paper.

PMID- 25968772
TI  - Range-resolved interferometric signal processing using sinusoidal optical
      frequency modulation.
AB  - A novel signal processing technique using sinusoidal optical frequency modulation
      of an inexpensive continuous-wave laser diode source is proposed that allows
      highly linear interferometric phase measurements in a simple, self-referencing
      setup. Here, the use of a smooth window function is key to suppress unwanted
      signal components in the demodulation process. Signals from several
      interferometers with unequal optical path differences can be multiplexed, and, in
      contrast to prior work, the optical path differences are continuously variable,
      greatly increasing the practicality of the scheme. In this paper, the theory of
      the technique is presented, an experimental implementation using three
      multiplexed interferometers is demonstrated, and detailed investigations
      quantifying issues such as linearity and robustness against instrument drift are
      performed. 

PMID- 25968773
TI  - Continuous angle steering of an optically- controlled phased array antenna based
      on differential true time delay constituted by micro-optical components.
AB  - We propose an optically controlled phased array antenna (PAA) based on
      differential true time delay constructed optical beamforming network (OBFN).
      Differential true time delay is realized by stack integrated micro-optical
      components. Optically-controlled angle steering of radio frequency (RF) beams are
      realized and demonstrated by this configuration. Experimental results demonstrate
      that OBFN based PAA can accomplish RF-independent broadband beam steering without
      beam squint effect and can achieve continuous angle steering. In addition, multi
      beams for different steering angles are acquired synchronously. 

PMID- 25968774
TI  - Pilot clinical study to investigate the human whole blood spectrum
      characteristics in the sub-THz region.
AB  - We have conducted a pilot clinical study to not only investigate the sub-THz
      spectra of ex-vivo fresh human whole blood of 28 patients following 8-hours
      fasting guideline, but also to find out the critical blood ingredients of which
      the concentration dominantly affects those sub-THz spectra. A great difference
      between the sub-THz absorption properties of human blood among different people
      was observed, while the difference can be up to ~15% of the averaged absorption
      coefficient of the 28 samples. Our pilot clinical study indicates that
      triglycerides and the number of red blood cells were two dominant factors to have
      significant negative correlation to the sub-THz absorption coefficients. 

PMID- 25968775
TI  - Free space millimeter wave-coupled electro-optic high speed nonlinear polymer
      phase modulator with in-plane slotted patch antennas.
AB  - We report in-plane slotted patch antenna-coupled electro-optic phase modulators
      with a carrier-to-sideband ratio (CSR) of 22 dB under an RF power density of 120
      W/m(2) and a figure of merit of 2.0 W(-1/2) at the millimeter wave frequencies of
      36-37 GHz based on guest-host type of second-order nonlinear polymer SEO125. CSR
      was improved more than 20 dB by using a SiO(2) protection layer. We demonstrate
      detection of 3 GHz modulation of the RF carrier. We also derive closed-form
      expressions for the modulated phase of optical wave and carrier-to-sideband
      ratio. Design, simulation, fabrication, and experimental results are discussed.

PMID- 25968776
TI  - Microfluidic flowmeter based on micro "hot-wire" sandwiched Fabry-Perot
      interferometer.
AB  - We present a compact microfluidic flowmeter based on Fabry-Perot interferometer
      (FPI). The FPI was composed by a pair of fiber Bragg grating reflectors and a
      micro Co(2+)-doped optical fiber cavity, acting as a "hot-wire" sensor.
      Microfluidic channels made from commercial silica capillaries were integrated
      with the FPIs on a chip to realize flow-rate sensing system. By utilizing a
      tunable pump laser with wavelength of 1480 nm, the proposed flowmeter was
      experimentally demonstrated. The flow rate of the liquid sample is determined by
      the induced resonance wavelength shift of the FPI. The effect of the pump power,
      microfluidic channel scale and temperature on the performance of our flowmeter
      was investigated. The dynamic response was also measured under different flow
      rate conditions. The experimental results achieve a sensitivity of 70 pm/(MUL/s),
      a dynamic range up to 1.1 MUL/s and response time in the level of seconds, with a
      spatial resolution ~200 MUm. Such good performance renders the sensor a promising
      supplementary component in microfluidic biochemical sensing system. Furthermore,
      simulation modal was built up to analyze the heat distribution of the "hot-wire"
      cavity and optimize the FPI structure as well.

PMID- 25968777
TI  - Topographic optical profilometry of steep slope micro-optical transparent
      surfaces.
AB  - Optical profilometers based on light reflection may fail at surfaces presenting
      steep slopes and highly curved features. Missed light, interference and
      diffraction at steps, peaks and valleys are some of the reasons. Consequently,
      blind areas or profile artifacts may be observed when using common reflection
      micro-optical profilometers (confocal, scanning interferometers, etc...). The
      Topographic Optical Profilometry by Absorption in Fluids (TOPAF) essentially
      avoids these limitations. In this technique an absorbing fluid fills the gap
      between a reference surface and the surface to profile. By comparing transmission
      images at two different spectral bands we obtain a reliable topographic map of
      the surface. In this contribution we develop a model to obtain the profile under
      micro-optical observation, where high numerical aperture (NA) objectives are
      mandatory. We present several analytical and experimental results, validating the
      technique's capabilities for profiling steep slopes and highly curved micro
      optical surfaces with nanometric height resolution. 

PMID- 25968778
TI  - Algorithm for evaluation of temperature distribution of a vapor cell in a diode
      pumped alkali laser system (part II).
AB  - With high efficiency and small thermally-induced effects in the near-infrared
      wavelength region, a diode-pumped alkali laser (DPAL) is regarded as combining
      the major advantages of solid-state lasers and gas-state lasers and obviating
      their main disadvantages at the same time. Studying the temperature distribution
      in the cross-section of an alkali-vapor cell is critical to realize high-powered
      DPAL systems for both static and flowing states. In this report, a theoretical
      algorithm has been built to investigate the features of a flowing-gas DPAL system
      by uniting procedures in kinetics, heat transfer, and fluid dynamic together. The
      thermal features and output characteristics have been simultaneously obtained for
      different gas velocities. The results have demonstrated the great potential of
      DPALs in the extremely high-powered laser operation. 

PMID- 25968779
TI  - Optimization of sharp and viewing-angle-independent structural color.
AB  - Structural coloration produces some of the most brilliant colors in nature and
      has many applications. Motivated by the recently proposed transparent displays
      that are based on wavelength-selective scattering, here we consider the new
      problem of transparent structural color, where objects are transparent under
      omnidirectional broad-band illumination but scatter strongly with a directional
      narrow-band light source. Transparent structural color requires two competing
      properties, narrow bandwidth and broad viewing angle, that have not been
      demonstrated simultaneously previously. Here, we use numerical optimization to
      discover geometries where a sharp 7% bandwidth in scattering is achieved, yet the
      peak wavelength varies less than 1%, and the peak height and peak width vary less
      than 6% over broad viewing angles (0-90 degrees ) under a directional
      illumination. Our model system consists of dipole scatterers arranged into
      several rings; interference among the scattered waves is optimized to yield the
      wavelength-selective and angle-insensitive response. 

PMID- 25968780
TI  - High energy 3 um ultrafast pulsed fiber laser.
AB  - In the paper, a 3 um mid-infrared (MIR) high energy ultrafast Er:ZBLAN fiber
      laser and amplification system is presented. The 3um seed pulses were generated
      through an Yb-doped ultrafast fiber laser pumped optical parametric amplification
      (OPA). A pulse energy of 12.4 uJ is generated at a repetition rate of 100 kHz
      with a pulse duration of 103 fs. A Er:ZBLAN fiber amplifier was used to further
      boost the chirped pulse energy to 84 uJ. 

PMID- 25968781
TI  - Novel approach for chirp and output power compensation applied to a 40-Gbit/s
      EADFB laser integrated with a short SOA.
AB  - We propose a novel approach for simultaneously controlling the chirp and
      increasing the output power of an EADFB laser by monolithically integrating a
      short-cavity SOA. We achieved a 40-Gbit/s 5-km SMF transmission at a wavelength
      of 1.55 MUm by using an EADFB SOA with a lower power consumption than a stand
      alone EADFB laser. 

PMID- 25968782
TI  - Interference patterns and extinction ratio of the diatom Coscinodiscus granii.
AB  - We report experimental and theoretical verification of the nature and position of
      multiple interference points of visible light transmitted through the valve of
      the centric diatom species Coscinodiscus granii. Furthermore, by coupling the
      transmitted light into an optical fiber and moving the diatom valve between
      constructive and destructive interference points, an extinction ratio of 20 dB is
      shown. 

PMID- 25968783
TI  - Random phase-free computer-generated hologram.
AB  - Addition of random phase to the object light is required in computer-generated
      holograms (CGHs) to widely diffuse the object light and to avoid its
      concentration on the CGH; however, this addition causes considerable speckle
      noise in the reconstructed image. For improving the speckle noise problem,
      techniques such as iterative phase retrieval algorithms and multi-random phase
      method are used; however, they are time consuming and are of limited
      effectiveness. Herein, we present a simple and computationally inexpensive method
      that drastically improves the image quality and reduces the speckle noise by
      multiplying the object light with the virtual convergence light. Feasibility of
      the proposed method is shown using simulations and optical reconstructions;
      moreover, we apply it to lens-less zoom-able holographic projection. The proposed
      method is useful for the speckle problems in holographic applications. 

PMID- 25968784
TI  - Electrothermally actuated tip-tilt-piston micromirror with integrated varifocal
      capability.
AB  - MEMS micromirrors have proven to be very important optical devices with
      applications ranging from steerable mirrors for switches and cross-connects to
      spatial light modulators for correcting optical distortions. Usually beam
      steering and focusing are done with different MEMS devices and tilt angles in
      excess of 10 degrees are seldom obtained. Here we describe a single MEMS device
      that combines tip/tilt, piston mode and varifocal capability into a single, low
      cost device with very large tilt angles. Our device consists of a 400 micron
      diameter mirror driven with thermal bimorphs. We have demonstrated deflection
      angles of +/- 40 degrees along both axes, a tunable focal length which varies
      between -0.48 mm to + 20.5 mm and a piston mode range of 300 microns - four
      separately controllable degrees of freedom in a single device. Potential
      applications range from smart lighting to optical switches and devices for
      telecom systems. 

PMID- 25968785
TI  - Study on weak-light photovoltaic characteristics of solar cell with a microgroove
      lens array on glass substrate.
AB  - Microgroove lens with 500-800 um in depth is proposed on the glass substrate of
      thin-film solar cell. The objective is to improve photovoltaic characteristics
      under weak-light illumination. First, the micro-optical characteristics were
      theoretically studied in connection with micro-lens structure; then a diamond
      micro-grinding was employed to fabricate microgroove lens; finally, indoor
      conversion efficiency and outdoor electrical generation were measured. It is
      shown that the 800-um-depth microgroove lens is able to absorb and scatter the
      inclined light to solar cell for improving weak-light conversion efficiency. It
      enhances the electricity generation by 118% and 185% in cloudy and overcast days,
      respectively. 

PMID- 25968786
TI  - Efficient hybrid white light-emitting diodes by organic-inorganic materials at
      different CCT from 3000K to 9000K.
AB  - The hybrid white light-emitting didoes (LED) with polyfluoren (PFO) polymer and
      quantum dot (QD) was investigated using dispensing method at the different
      correlated color temperature (CCT) for cool and warm color temperature. This
      result indicates that the hybrid white LED device has the higher luminous
      efficiency than the convention one, which could be attributed to the increased
      utilization rate of the UV light. Furthermore, the CIE 1931 coordinate of high
      quality white hybrid LED with different CCT range from 3000K to 9000K is
      demonstrated. Consequently, the angular-dependent CCT and the thermal issue of
      the hybrid white LED device were also analyzed in this study. 

PMID- 25968787
TI  - Device performance of inverted polymer solar cells with AgSiO(2) nanoparticles in
      active layer.
AB  - Localized surface plasmon mediated polymer solar cells (PSCs) were fabricated
      using the Ag/SiO(2) nanoparticles (NPs). The inverted PSC structure without poly
      (3,4-ethylenedioxythiophene) polystyrene sulfonate ( PEDOT: PSS) was prepared due
      to the efficient insertion of Ag/SiO(2) NPs in the vicinity of active layer,
      which led to an enhancement in photo-conversion efficiency (PCE). This
      enhancement mainly comes from the light scattering by the SiO(2) shell and the
      localized surface plasmon effect by the Ag core, but we also considered the
      structural issues such as the NP distribution, the swelling of the active layer
      and of the metal electrode.

PMID- 25968788
TI  - Bias-dependence of luminescent coupling efficiency in multijunction solar cells.
AB  - In this work, we demonstrate an improved method to simulate the characteristics
      of multijunction solar cell by introducing a bias-dependent luminescent coupling
      efficiency. The standard two-diode equivalent-circuit model with constant
      luminescent coupling efficiency has limited accuracy because it does not include
      the recombination current from photogenerated carriers. Therefore, we propose an
      alternative analytical method with bias-dependent luminescent coupling efficiency
      to model multijunction cell behavior. We show that there is a noticeable
      difference in the J-V characteristics and cell performance generated by
      simulations with a constant vs. bias-dependent coupling efficiency. The results
      indicate that introducing a bias-dependent coupling efficiency produces more
      accurate modeling of multijunction cell behavior under real operating conditions.

PMID- 25968789
TI  - Warm-white light-emitting diode with high color rendering index fabricated by
      combining trichromatic InGaN emitter with single red phosphor.
AB  - We present a trichromatic GaN-based light-emitting diode (LED) that emits near
      ultraviolet (n-UV) blue and green peaks combined with red phosphor to generate
      white light with a low correlated color temperature (CCT) and high color
      rendering index (CRI). The LED structure, blue and green unipolar InGaN/GaN
      multiple quantum wells (MQWs) stacked with a top p-i-n structure containing an
      InGaN/GaN MQW emitting n-UV light, was grown epitaxially on a single substrate.
      The trichromatic LED chips feature a vertical conduction structure on a silicon
      substrate fabricated through wafer bonding and laser lift-off techniques. The
      blue and green InGaN/GaN MQWs were pumped with n-UV light to re-emit low-energy
      photons when the LEDs were electrically driven with a forward current. The
      emission spectrum included three peaks at approximately 405, 468, and 537 nm.
      Furthermore, the trichromatic LED chips were combined with red phosphor to
      generate white light with a CCT and CRI of approximately 2900 and 92,
      respectively. 

PMID- 25968790
TI  - Graphene-assisted Si-InSb thermophotovoltaic system for low temperature
      applications.
AB  - The present work theoretically analyzes the performance of the near-field
      thermophotovoltaic (TPV) energy conversion device for low temperature
      applications (Tsource ~ 500 K). In the proposed TPV system, doped Si is employed
      as the source because its optical property can be readily tuned by changing the
      doping concentration, and InSb is selected as a TPV cell because of its low
      bandgap energy (0.17 eV). In order to enhance the near-field thermal radiation
      between the source and the TPV cell, monolayer of graphene is coated on the cell
      side so that surface plasmon can play a critical role in heat transfer. It is
      found that monolayer of graphene can significantly enhance the power throughput
      by 30 times and the conversion efficiency by 6.1 times compared to the case
      without graphene layer. The resulting maximum conversion efficiency is 19.4% at
      10-nm vacuum gap width. 

PMID- 25968791
TI  - Laser perforated ultrathin metal films for transparent electrode applications.
AB  - Transmittance and conductivity are the key requirements for transparent
      electrodes. Many optoelectronic applications require additional features such as
      mechanical flexibility and cost-efficient fabrication at low temperatures. Here
      we demonstrate a simple method to fabricate high performance transparent
      electrodes that is based on perforation of thin silver layers using picosecond
      laser pulses. Transparent electrodes have been characterized optically and
      electrically in order to determine the influence of specific surface coverage.
      Special attention was paid to maintaining sufficient conductivity in the metal
      free areas. As a result, transmittance of a much higher bandwidth was achieved as
      compared to unpatterned metal films. Transparent electrodes have been fabricated
      on glass and plastic foil, as well as wafer-based silicon heterojunction solar
      cells, demonstrating their applicability for most relevant cases. 

PMID- 25968792
TI  - CH(3)NH(3)PbI(3) perovskite / silicon tandem solar cells: characterization based
      optical simulations.
AB  - In this study we analyze and discuss the optical properties of various tandem
      architectures: mechanically stacked (four-terminal) and monolithically integrated
      (two-terminal) tandem devices, consisting of a methyl ammonium lead triiodide
      (CH(3)NH(3)PbI(3)) perovskite top solar cell and a crystalline silicon bottom
      solar cell. We provide layer thickness optimization guidelines and give estimates
      of the maximum tandem efficiencies based on state-of-the-art sub cells. We use
      experimental complex refractive index spectra for all involved materials as input
      data for an in-house developed optical simulator CROWM. Our characterization
      based simulations forecast that with optimized layer thicknesses the four
      terminal configuration enables efficiencies over 30%, well above the current
      single-junction crystalline silicon cell record of 25.6%. Efficiencies over 30%
      can also be achieved with a two-terminal monolithic integration of the sub-cells,
      combined with proper selection of layer thicknesses.

PMID- 25968793
TI  - Luminescence from oriented emitting dipoles in a birefringent medium.
AB  - We present an optical model to describe the luminescence from oriented emitting
      dipoles in a birefringent medium and validate the theoretical model through its
      applications to a dye doped organic thin film and organic light emitting diodes
      (OLEDs). We demonstrate that the optical birefringence affects not only far-field
      radiation characteristics such as the angle-dependent emission spectrum and
      intensity from the thin film and OLEDs, but also the outcoupling efficiency of
      OLEDs. The orientation of emitting dipoles in a birefringent medium is
      successfully analyzed from the far-field radiation pattern of a thin film using
      the model. In addition, the birefringent model presented here provides a precise
      analysis of the angle-dependent EL spectra and efficiencies of OLEDs with the
      determined emitting dipole orientation. 

PMID- 25968794
TI  - Optical enhancement brought by doping Gd(3+) ions into Ce: YAG ceramics for
      indoor white light-emitting diodes.
AB  - We dope Gd(3+) ions into Ce: YAG ceramics to induce red-shift in the
      photoluminescence, of which the degree is proportional to the Gd(3+) doping
      concentration. This kind of ceramic, when collaborating with InGaN blue chips,
      proves to be a promising fluorescent material of white light-emitting diodes, for
      not only its high in-line transmittance and decent quantum yield, but also the
      improvement in color rendering ability brought by the red-shift, which enhances
      the ratio of red portion in spectra. We demonstrate that 10% is the optimized
      value of Gd(3+) doping concentration, as it provides the maximum color rendering
      index of ~78 with luminous efficiency as high as 128 lm/W.

PMID- 25968795
TI  - Selective radiative heating of nanostructures using hyperbolic metamaterials.
AB  - Hyperbolic metamaterials (HMM) are of great interest due to their ability to
      break the diffraction limit for imaging and enhance near-field radiative heat
      transfer. Here we demonstrate that an annular, transparent HMM enables selective
      heating of a sub-wavelength plasmonic nanowire by controlling the angular mode
      number of a plasmonic resonance. A nanowire emitter, surrounded by an HMM,
      appears dark to incoming radiation from an adjacent nanowire emitter unless the
      second emitter is surrounded by an identical lens such that the wavelength and
      angular mode of the plasmonic resonance match. Our result can find applications
      in radiative thermal management. 

PMID- 25968796
TI  - Red-blue-green solid state light sources using a narrow line-width green
      phosphor.
AB  - We demonstrate that using a narrow line-width green phosphor with the peak
      wavelength closely aligned with the peak in the human eye sensitivity
      significantly improves the Luminous Efficacy of Radiation (LER) for Red-Green
      Blue (RGB) emitters. Compared to the traditional RGB sources, the improvement in
      LER of 20 lm/W can be achieved. Combining the narrow band green phosphor with
      conventional wide band red and blue phosphors allows for trading off these
      improvements against the deviation from the Planckian locus for even higher LER.
      The light sources with the narrow line green phosphor are particularly promising
      for high energy efficiency and high intensity illumination, where somewhat
      compromises can be made in the color quality such as in automotive, outdoor
      spaces, industrial ware-houses, public places (train stations, airports) etc.. 

PMID- 25968797
TI  - Flexible CdTe/CdS solar cells on thin glass substrates.
AB  - We demonstrate flexible CdTe/CdS thin-film solar cells in a superstrate
      configuration with a cell conversion efficiency as high as 10.9%. We deposit a
      CdS window layer and a CdTe absorber layer on a flexible glass substrate using
      the chemical bath deposition method and close-spaced sublimation method,
      respectively. The thin and flexible glass substrates were able to tolerate a high
      growth temperature and post-growth processes. We repeatedly apply a strain of
      0.15% to the fabricated CdTe/CdS solar cells, and this was shown to have a
      negligible effect on their performances. Our proposed thin films-on-compliant
      substrate structure, which was prepared by replacing a rigid glass with a
      bendable one, demonstrated flexible CdTe/CdS p-n junction thin-film solar cells
      without compromising the cell performance. 

PMID- 25968798
TI  - Broadband antireflective nano-cones for tandem solar cells.
AB  - Broadband solar cell antireflection coatings made of nano-cones are studied in
      square lattices of ZnS, TiO(2) and Si(3)N(4). In the best case, the spectrally
      integrated transmittance (accounting for both reflection and dielectric
      absorption losses) for direct solar radiation is 99 %, which represents a four
      fold decrease in transmission losses in comparison to a standard antireflective
      coating bilayer. The dependence of the transmission as a function of
      nanostructure dimensions is studied, showing a wide maximum, thus leading to a
      high tolerance for manufacturing errors. This high transmittance is also robust
      against deviations from normal incidence. Our analysis suggests that the high
      transmittance is due not only to an effective gradual index effect, but is also
      due to light coupling to quasiguided modes in the photonic crystal leaking mostly
      towards the substrate.

PMID- 25968799
TI  - GaN-based ultraviolet light-emitting diodes with AlN/GaN/InGaN multiple quantum
      wells.
AB  - We demonstrate indium gallium nitride/gallium nitride/aluminum nitride
      (AlN/GaN/InGaN) multi-quantum-well (MQW) ultraviolet (UV) light-emitting diodes
      (LEDs) to improve light output power. Similar to conventional UV LEDs with
      AlGaN/InGaN MQWs, UV LEDs with AlN/GaN/InGaN MQWs have forward voltages (V(f)'s)
      ranging from 3.21 V to 3.29 V at 350 mA. Each emission peak wavelength of
      AlN/GaN/InGaN MQW UV LEDs presents 350 mA output power greater than that of the
      corresponding emission peak wavelength of AlGaN/InGaN MQW UV LEDs. The light
      output power at 350mA of AlN/GaN/InGaN MQWs UV LEDs with 375 nm emission
      wavelength can reach around 26.7% light output power enhancement in magnitude
      compared to the AlGaN/InGaN MQWs UV LEDs with same emission wavelength. But 350mA
      light output power of AlN/GaN/InGaN MQWs UV LEDs with emission wavelength of
      395nm could only have light output power enhancement of 2.43% in magnitude
      compared with the same emission wavelength AlGaN/InGaN MQWs UV LEDs. Moreover,
      AlN/GaN/InGaN MQWs present better InGaN thickness uniformity, well/barrier
      interface quality and less large size pits than AlGaN/InGaN MQWs, causing
      AlN/GaN/InGaN MQW UV LEDs to have less reverse leakage currents at -20 V.
      Furthermore, AlN/GaN/InGaN MQW UV LEDs have the 2-kV human body mode (HBM)
      electrostatic discharge (ESD) pass yield of 85%, which is 15% more than the 2-kV
      HBM ESD pass yield of AlGaN/InGaN MQW UV LEDs of 70%.

PMID- 25968800
TI  - Performance evaluation of four directional emissivity analytical models with
      thermal SAIL model and airborne images.
AB  - Land surface emissivity is a crucial parameter in the surface status monitoring.
      This study aims at the evaluation of four directional emissivity models,
      including two bi-directional reflectance distribution function (BRDF) models and
      two gap-frequency-based models. Results showed that the kernel-driven BRDF model
      could well represent directional emissivity with an error less than 0.002, and
      was consequently used to retrieve emissivity with an accuracy of about 0.012 from
      an airborne multi-angular thermal infrared data set. Furthermore, we updated the
      cavity effect factor relating to multiple scattering inside canopy, which
      improved the performance of the gap-frequency-based models. 

PMID- 25968801
TI  - Rayfiles including spectral and colorimetric information.
AB  - To obtain realistic results in lighting simulation software, realistic models of
      light sources are needed. A near-field model of a light source is accurate, and
      can be obtained by a near-field goniophotometer. This type of goniophotometer is
      conventionally equipped with a V(lambda)-filter. However, the advent of new light
      sources with spatial- or angular color variations necessitates the inclusion of
      spectral information about the source. We demonstrate a method to include
      spectral information of a light source in ray tracing. We measured the relative
      angular variation of the spectrum of an OLED using a spectroradiometer mounted on
      a near-field goniophotometer. Principal component analysis (PCA) is exploited to
      reduce the amount of data that needs to be stored. Also a photometric ray file of
      the OLED was obtained. To construct a set of monochromatic ray files, the
      luminous flux in the original ray file is redistributed over a set of wavelengths
      and stored in separate ray files. The redistribution depends on the angle of
      emission and the spectral irradiance measured in that direction. These ray files
      are then inserted in ray tracing software TracePro. Using the OLED as a test
      source, the absolute spectral irradiance is calculated at an arbitrary position.
      The result is validated using a spectroradiometer to obtain the absolute spectral
      irradiance at that particular point. A good agreement between the simulated and
      measured absolute spectral irradiance is found. Furthermore, a set of tristimulus
      ray files is constructed and used in ray tracing software to generate a u'v'
      color coordinate distribution on a surface. These values are in agreement with
      the color coordinate distribution found using the spectral ray files. Whenever
      spectral or color information is desired at a task area, the proposed method
      allows for a fast and efficient way to improve the accuracy of simulations using
      ray tracing. 

PMID- 25968802
TI  - GaN-based photon-recycling green light-emitting diodes with vertical-conduction
      structure.
AB  - A p-i-n structure with near-UV(n-UV) emitting InGaN/GaN multiple quantum
      well(MQW) structure stacked on a green unipolar InGaN/GaN MQW was epitaxially
      grown at the same sapphire substrate. Photon recycling green light-emitting
      diodes(LEDs) with vertical-conduction feature on silicon substrates were then
      fabricated by wafer bonding and laser lift-off techniques. The green InGaN/GaN
      QWs were pumped with n-UV light to reemit low-energy photons when the LEDs were
      electrically driven with a forward current. Efficiency droop is potentially
      insignificant compared with the direct green LEDs due to the increase of
      effective volume of active layer in the optically pumped green LEDs, i.e., light
      emitting no longer limited in the QWs nearest to the p-type region to cause
      severe Auger recombination and carrier overflow losses. 

PMID- 25968803
TI  - The realistic energy yield potential of GaAs-on-Si tandem solar cells: a
      theoretical case study.
AB  - Si based tandem solar cells represent an alternative to traditional compound III
      V multijunction cells as a promising way to achieve high efficiencies. A
      theoretical study on the energy yield of GaAs on Si (GaAs/Si) tandem solar cells
      is performed to assess their energy yield potential under realistic illumination
      conditions with varying spectrum. We find that the yield of a 4-terminal contact
      scheme with thick top cell is more than 15% higher than for a 2-terminal scheme.
      Furthermore, we quantify the main losses that occur for this type of solar cell
      under varying spectra. Apart from current mismatch, we find that a significant
      power loss can be attributed to low irradiance seen by the sub-cells. The study
      shows that despite non-optimal bandgap combination, GaAs/Si tandem solar cells
      have the potential to surpass 30% energy conversion efficiency. 

PMID- 25968804
TI  - Light trapping efficiency comparison of Si solar cell textures using spectral
      photoluminescence.
AB  - The band-to-band absorption enhancement due to various types of light trapping
      structures is studied experimentally with photoluminescence (PL) on
      monocrystalline silicon wafers. Four basic light trapping structures are
      examined: reactive ion etched texture (RIE), metal-assisted etched texture (MET),
      random pyramid texture (RAN) and plasmonic Ag nanoparticles with a diffusive
      reflector (Ag/DR). We also compare two novel combined structures of front side
      RIE/rear side RAN and front side RIE/rear side Ag/DR. The use of
      photoluminescence allows us to measure the absorption due to band-to-band
      transitions only, and excludes parasitic absorption from free carriers and other
      sources. The measured absorptance spectra are used to calculate the maximum
      generation current for each structure, and the light trapping efficiency is
      compared to a recently-proposed figure of merit. The results show that by
      combining RIE with RAN and Ag/DR, we can fabricate two structures with excellent
      light trapping efficiencies of 55% and 52% respectively, which is well above
      previously reported values for similar wafer thicknesses. A comparison of the
      measured band-band absorption and the EQE of back-contact silicon solar cells
      demonstrates that PL extracted absorption provides a very good indication of long
      wavelength performance for high efficiency silicon solar cells. 

PMID- 25968805
TI  - White emission from non-planar InGaN/GaN MQW LEDs grown on GaN template with
      truncated hexagonal pyramids.
AB  - Non-planar InGaN/GaN multiple quantum well (MQW) structures are grown on a GaN
      template with truncated hexagonal pyramids (THPs) featuring c-plane and r-plane
      surfaces. The THP array is formed by the regrowth of the GaN layer on a selective
      area Si-implanted GaN template. Transmission electron microscopy shows that the
      InGaN/GaN epitaxial layers regrown on the THPs exhibit different growth rates and
      indium compositions of the InGaN layer between the c-plane and r-plane surfaces.
      Consequently, InGaN/GaN MQW light-emitting diodes grown on the GaN THP array emit
      multiple wavelengths approaching near white light. 

PMID- 25968806
TI  - Expression of VEGFs and its receptors in abdominal aortic aneurysm.
AB  - AIM: The development of abdominal aortic aneurysm (AAA) is thought to be related
      to an imbalance of VEGF and its receptors. This study aimed at evaluating the
      expression of VEGF family members and their receptors in AAA wall, AAA mural
      thrombus and normal aorta wall. METHODS: AAA specimens (mural thrombus-luminal
      layer, mural thrombus-abluminal layer, AAA wall) were collected from 24 patients
      undergoing elective open AAA repair. Abdominal aortas from 12 organ donors served
      as controls. The expression of VEGF (VEGF-A, VEGF-B, VEGF-C and VEGF-D) and VEGF
      receptors (VEGFR-1, VEGFR-2 and VEGFR-3) was evaluated using Western blot.
      RESULTS: Increased expression of VEGF-B (269+/-31%), VEGF-C (1065+/-92%) and VEGF
      D (145+/-12%) was found in AAA wall, when compared to normal aorta (P<0.01). No
      significant difference in VEGF-A expression was demonstrated between AAA and
      normal aortic wall (P>0.01). Mural thrombus (abluminal/luminal) expression of
      VEGF-A (172+/-22%/133+/-17%), VEGF-B (308+/-24% / 363+/-28%), VEGF-C (1496+/
      110%/830+/-58%) and VEGF-D (200+/-18%/142+/-12%) was increased in comparison with
      normal aorta (P<0.01). Furthermore, VEGF-C and VEGF-D expression was increased in
      mural thrombus abluminal layer, when compared to its luminal layer (1496+/-110%
      vs. 830+/-58% and 200+/-18% vs. 142+/-12%, P<0.01). VEGFR-1 expression was
      increased only in luminal and abluminal layers of mural thrombus (377+/-58% and
      2188+/-196%, P<0.01). In comparison with normal aorta, all aneurysm samples (AAA
      wall, mural thrombus abluminal and luminal layers) expressed higher levels of
      VEGFR-2 (565+/-52%, 1057+/-125%, 537+/-54%, P<0.01) and VEGFR-3 (233+/-18%, 197+/
      17%, 193+/-16%, P<0.01). CONCLUSIONS: Our study demonstrates that the abluminal
      layer in AAA mural thrombus contains high levels of VEGFs and VEGF receptors,
      suggesting that this layer may play a significant role in AAA disease
      pathogenesis. Increased expressions of VEGF and their receptors in AAA mural
      thrombus may impact different pathways involved in AAA etiology.

PMID- 25968808
TI  - Serum paraoxonase and arylesterase activities in patients with chronic otitis
      media.
AB  - OBJECTIVES: Paraoxonase-1 (PON1) prevents oxidative stress by inhibiting the
      oxidation of cell membrane lipids by the reactive oxygen species that form during
      acute and chronic inflammation. The aim of this study was to investigate serum
      PON1 activity and oxidative stress in patients with chronic otitis media (COM).
      METHODS: Fifty consecutive patients with COM and 55 controls were enrolled in the
      present study. The patients were divided into two groups according to the
      presence of cholesteatoma. The serum PON1 arylesterase activities and lipid
      hydroperoxide (LOOH) levels were determined. RESULTS: Serum paraoxonase and
      arylesterase activities were significantly lower in the COM patients than in the
      controls (P < 0.001 for all comparisons), whereas the LOOH levels were
      significantly higher (P < 0.001). DISCUSSION: These results indicated that a
      lower level of PON1 activity was associated with an oxidant-antioxidant
      imbalance. In addition, decreased PON1 activity may play an important role in the
      pathophysiology of COM.

PMID- 25968807
TI  - Prevalence and detection of psychosocial problems in cancer genetic counseling.
AB  - Only a minority of individuals who undergo cancer genetic counseling experience
      heightened levels of psychological distress, but many more experience a range of
      cancer genetic-specific psychosocial problems. The aim of this study was to
      estimate the prevalence of such psychosocial problems, and to identify possible
      demographic and clinical variables associated significantly with them. Consenting
      individuals scheduled to undergo cancer genetic counseling completed the
      Psychosocial Aspects of Hereditary Cancer (PAHC) questionnaire, the Hospital
      Anxiety and Depression Scale (HADS) and the Distress Thermometer (DT) prior to or
      immediately following their counseling session. More than half of the 137
      participants reported problems on three or more domains of the PAHC, most often
      in the domains 'living with cancer' (84%), 'family issues' (46%), 'hereditary
      predisposition' (45%), and 'child-related issues' (42%). Correlations between the
      PAHC, the HADS and the DT were low. Previous contact with a psychosocial worker,
      and having a personal history of cancer were associated significantly with HADS
      scores, but explained little variance (9%). No background variables were
      associated significantly with the DT. Previous contact with a psychosocial
      worker, and having children were significantly associated with several PAHC
      domains, again explaining only a small percentage of the variance (2-14%). The
      majority of counselees experience specific cancer genetic counseling-related
      psychosocial problems. Only a few background variables are associated
      significantly with distress or psychosocial problems. Thus we recommend using the
      PAHC or a similar problem-oriented questionnaire routinely in cancer genetic
      counseling to identify individuals with such problems.

PMID- 25968810
TI  - Bathing Frequency Recommendations for Children with Atopic Dermatitis: Results of
      Three Observational Pilot Surveys.
AB  - The results from three online surveys of dermatologists, allergists and
      immunologists, and primary care physicians (PCPs) regarding routine bathing
      frequency recommendations for children with atopic dermatitis (AD) are presented.
      The results suggest that PCPs approach bathing frequency differently than
      specialists, with PCPs recommending daily bathing less than 50% of the time and
      specialists recommending daily bathing more than 50% of the time. Because there
      is lack of consensus, studies are needed to evaluate whether bathing frequency
      makes a clinical difference in the treatment of pediatric AD. 

PMID- 25968811
TI  - Methodological approaches to evaluate the impact of FDA drug safety
      communications.
AB  - BACKGROUND: When the US FDA approves a new prescription drug there is still a
      great deal remaining to be learned about the safe and proper use of that product.
      When new information addressing these topics emerges post-approval, the FDA may
      issue a Drug Safety Communication (DSC) to alert patients and physicians. The
      effectiveness of the communication-how drug safety messaging conveyed in FDA DSCs
      changes patient or prescriber behavior-may depend on multiple factors, including
      the way physicians and patients learn about the information, their understanding
      of the issues conveyed, and their perception of the importance of the
      information. In 2013, the FDA issued two DSCs addressing critical new warnings
      related to products containing the sedative/hypnotic zolpidem. OBJECTIVE: In this
      article, we describe a core set of research initiatives that can be used to study
      how zolpidem-related DSCs affected subsequent physician and patient decision
      making. METHODS: These research initiatives include analyzing drug utilization
      patterns and related health outcomes; comparing zolpidem-containing products
      against a comparator with similar indications [eszopiclone (Lunesta)] not covered
      by the 2013 DSCs; and surveying patients and qualitatively evaluating the
      dissemination of information regarding these drugs in traditional and social
      media channels. CONCLUSIONS: Using an integrated, multidisciplinary approach, we
      can obtain information that can be used to optimize regulatory communications by
      seeking to understand the impact of the information contained in FDA risk
      communications.

PMID- 25968813
TI  - Quality of the hematopoietic stem cell graft affects the clinical outcome of
      allogeneic stem cell transplantation.
AB  - BACKGROUND: In approximately two-thirds of patients undergoing allogeneic
      hematopoietic stem cell transplantation (HSCT) no suitable related donor can be
      identified but an unrelated HLA-matched donor can be found through international
      donor registries. HSCT grafts from unrelated donors are commonly collected at
      distant sites. Therefore, graft storage and transportation becomes crucial in the
      HSCT process. We aimed to study the impact of graft quality on clinical outcome
      and identify factors affecting graft quality. STUDY DESIGN AND METHODS: We
      investigated the influence of graft quality on the clinical outcome in 144 HSCT
      patients. Graft quality was assessed by determining the viability (7
      aminoactinomycin D [7AAD]) on a frozen-thawed sample from the peripheral blood
      stem cell (PBSC) graft. RESULTS: Patients receiving PBSCs with inferior quality
      (i.e., viability < 64% in the frozen-thawed sample) more frequently developed
      acute graft-versus-host disease (aGVHD) Grades I to IV than patients receiving
      grafts with better quality (p = 0.025). The transplant-related mortality (TRM)
      was higher in the group receiving grafts with lower viability (p = 0.03). The
      viability of the frozen-thawed samples was highly variable (median, 64%; range,
      24%-96%). No correlation could be observed when comparing the viability in newly
      arrived PBSC grafts to frozen-thawed vials. Grafts with white blood cell (WBC)
      count of more than 300 * 10(9) /L had lower viability than those with lower WBC
      counts (p < 0.001). CONCLUSION: Graft quality affects clinical outcome. Patients
      receiving grafts with inferior quality had more aGVHD and higher TRM. There is a
      need for better analyses for assessing graft quality in routine HSCT care;
      analysis using 7AAD on fresh PBSC grafts is not sufficient.

PMID- 25968814
TI  - Copper-free arylation of 3,3-disubstituted allylic halides with triazene-softened
      aryl Grignard reagents.
AB  - A copper-free allylic arylation reaction between 3,3-disubstituted allylic
      halides and triazene-softened aryl Grignard reagents has been developed. This
      protocol presents a direct and efficient way to construct both alpha- or gamma
      isomers with high regioselectivity under environmentally benign conditions.
      Various functional groups can be tolerated in the reaction and the products are
      of high value for multiple synthetic applications. The alpha- and gamma-isomers
      can be converted to the corresponding 3H-indole and indole derivatives in
      multigram scale respectively. 

PMID- 25968815
TI  - Philip Rubin, MD, FASTRO: Reflections on a Radiation Oncology Pioneer.

PMID- 25968812
TI  - Harmonizing post-market surveillance of prescription drug misuse: a systematic
      review of observational studies using routinely collected data (2000-2013).
AB  - BACKGROUND: Prescription drug misuse is a growing public health concern globally.
      Routinely collected data provide a valuable tool for quantifying prescription
      drug misuse. OBJECTIVE: To synthesize the global literature investigating
      prescription drug misuse utilizing routinely collected, person-level
      prescription/dispensing data to examine reported measures, documented extent of
      misuse and associated factors. METHODS: The MEDLINE, EMBASE, CINAHL, MEDLINE In
      Process, Scopus citations and Google Scholar databases were searched for relevant
      articles published between 1 January 2000 and 31 July 2013. A total of 10,803
      abstracts were screened and 281 full-text manuscripts were retrieved. Fifty-two
      peer-reviewed, English-language manuscripts met our inclusion criteria-an
      aim/method investigating prescription drug misuse in adults and a measure of
      misuse derived exclusively from prescription/dispensing data. RESULTS: Four
      proxies of prescription drug misuse were commonly used across studies: number of
      prescribers, number of dispensing pharmacies, early refills and volume of drugs
      dispensed. Overall, 89 unique measures of misuse were identified across the 52
      studies, reflecting the heterogeneity in how measures are constructed: single or
      composite; different thresholds, cohort definitions and time period of
      assessment. Consequently, it was not possible to make definitive comparisons
      about the extent (range reported 0.01-93.5 %), variations and factors associated
      with prescription drug misuse. CONCLUSIONS: Routine data collections are
      relatively consistent across jurisdictions. Despite the heterogeneity of the
      current literature, our review identifies the capacity to develop universally
      accepted metrics of misuse applied to a core set of variables in
      prescription/dispensing claims. Our timely recommendations have the potential to
      unify the global research field and increase the capacity for routine
      surveillance of prescription drug misuse.

PMID- 25968816
TI  - Human papillomavirus and head and neck cancer.

PMID- 25968817
TI  - The expanding role of radiation oncology in Japan.

PMID- 25968818
TI  - The Red Journal's Outstanding Reviewer Awards for 2014.

PMID- 25968819
TI  - Cultivating Tomorrow's Clinician Scientists: We Reap What We Sow.

PMID- 25968820
TI  - Raising the next generation of physician-scientists: the chairs' perspective.

PMID- 25968821
TI  - A fork in the road: choosing the path of relevance.

PMID- 25968822
TI  - Medical Student Perspectives on a Multi-institutional Clerkship Curriculum: A
      Report From the Radiation Oncology Education Collaborative Study Group.

PMID- 25968823
TI  - Trends in the quality of treatment for patients with intact cervical cancer in
      the United States, 1999 through 2011.
AB  - PURPOSE: High-quality treatment for intact cervical cancer requires external
      radiation therapy, brachytherapy, and chemotherapy, carefully sequenced and
      completed without delays. We sought to determine how frequently current treatment
      meets quality benchmarks and whether new technologies have influenced patterns of
      care. METHODS AND MATERIALS: By searching diagnosis and procedure claims in
      MarketScan, an employment-based health care claims database, we identified 1508
      patients with nonmetastatic, intact cervical cancer treated from 1999 to 2011,
      who were <65 years of age and received >10 fractions of radiation. Treatments
      received were identified using procedure codes and compared with 3 quality
      benchmarks: receipt of brachytherapy, receipt of chemotherapy, and radiation
      treatment duration not exceeding 63 days. The Cochran-Armitage test was used to
      evaluate temporal trends. RESULTS: Seventy-eight percent of patients (n=1182)
      received brachytherapy, with brachytherapy receipt stable over time (Cochran
      Armitage Ptrend=.15). Among patients who received brachytherapy, 66% had high
      dose rate and 34% had low-dose rate treatment, although use of high-dose rate
      brachytherapy steadily increased to 75% by 2011 (Ptrend<.001). Eighteen percent
      of patients (n=278) received intensity modulated radiation therapy (IMRT), and
      IMRT receipt increased to 37% by 2011 (Ptrend<.001). Only 2.5% of patients (n=38)
      received IMRT in the setting of brachytherapy omission. Overall, 79% of patients
      (n=1185) received chemotherapy, and chemotherapy receipt increased to 84% by 2011
      (Ptrend<.001). Median radiation treatment duration was 56 days (interquartile
      range, 47-65 days); however, duration exceeded 63 days in 36% of patients
      (n=543). Although 98% of patients received at least 1 benchmark treatment, only
      44% received treatment that met all 3 benchmarks. With more stringent indicators
      (brachytherapy, >=4 chemotherapy cycles, and duration not exceeding 56 days),
      only 25% of patients received treatment that met all benchmarks. CONCLUSION: In
      this cohort, most cervical cancer patients received treatment that did not comply
      with all 3 benchmarks for quality treatment. In contrast to increasing receipt of
      newer radiation technologies, there was little improvement in receipt of
      essential treatment benchmarks.

PMID- 25968824
TI  - Subclinical cardiac dysfunction detected by strain imaging during breast
      irradiation with persistent changes 6 weeks after treatment.
AB  - PURPOSE: To evaluate 2-dimensional strain imaging (SI) for the detection of
      subclinical myocardial dysfunction during and after radiation therapy (RT).
      METHODS AND MATERIALS: Forty women with left-sided breast cancer, undergoing only
      adjuvant RT to the left chest, were prospectively recruited. Standard
      echocardiography and SI were performed at baseline, during RT, and 6 weeks after
      RT. Strain (S) and strain rate (Sr) parameters were measured in the longitudinal,
      circumferential, and radial planes. Correlation of change in global longitudinal
      strain (GLS % and Delta change) and the volume of heart receiving 30 Gy (V30) and
      mean heart dose (MHD) were examined. RESULTS: Left ventricular ejection fraction
      was unchanged; however, longitudinal systolic S and Sr and radial S were
      significantly reduced during RT and remained reduced at 6 weeks after treatment
      [longitudinal S (%) -20.44 +/- 2.66 baseline vs -18.60 +/- 2.70* during RT vs 
      18.34 +/- 2.86* at 6 weeks after RT; longitudinal Sr (s(-1)) -1.19 +/- 0.21 vs 
      1.06 +/- 0.18* vs -1.06 +/- 0.16*; radial S (%) 56.66 +/- 18.57 vs 46.93 +/-
      14.56* vs 49.22 +/- 15.81*; *P<.05 vs baseline]. Diastolic Sr were only reduced 6
      weeks after RT [longitudinal E Sr (s(-1)) 1.47 +/- 0.32 vs 1.29 +/- 0.27*;
      longitudinal A Sr (s(-1)) 1.19 +/- 0.31 vs 1.03 +/- 0.24*; *P<.05 vs baseline],
      whereas circumferential strain was preserved throughout. A modest correlation
      between S and Sr and V30 and MHD was observed (GLS Delta change and V30 rho =
      0.314, P=.05; GLS % change and V30 rho = 0.288, P=.076; GLS Delta change and MHD
      rho = 0.348, P=.03; GLS % change and MHD rho = 0.346, P=.031). CONCLUSIONS:
      Subclinical myocardial dysfunction was detected by 2-dimensional SI during RT,
      with changes persisting 6 weeks after treatment, though long-term effects remain
      unknown. Additionally, a modest correlation between strain reduction and
      radiation dose was observed.

PMID- 25968825
TI  - Lobulated enhancement evaluation in the follow-up of liver metastases treated by
      stereotactic body radiation therapy.
AB  - OBJECTIVE: The Response Evaluation Criteria in Solid Tumors (RECIST) can have
      limitations when used to evaluate local treatments for cancer, especially for
      liver malignancies treated by stereotactic body radiation therapy (SBRT). The aim
      of this study was to validate the relationship between the occurrence of
      lobulated enhancement (LE) and local relapse and to evaluate the utility of this
      relationship for predicting local progression. PATIENTS AND METHODS: Imaging data
      of 59 lesions in 46 patients, including 281 computed tomographic (CT) scans, were
      retrospectively and blindly reviewed by 3 radiologists. One radiologist measured
      the lesion size, for each CT and overall, to classify responses using RECIST
      threshold criteria. The second studied LE occurrence. A third radiologist was
      later included and studied LE occurrence to evaluate the interobserver
      consistency for LE evaluation. RESULTS: The mean duration of follow-up was 13.6
      months. LE was observed in 16 of 18 progressive lesions, occurring before size
      based progression in 50% of cases, and the median delay of LE detection was 3.2
      months. The sensitivity of LE to predict progression was 89%, and its specificity
      was 100%. The positive predictive value was 100%, the negative predictive value
      was 95.3%, and the overall accuracy was 97%. The probability of local progression
      free survival at 12 months was significantly higher for lesions without LE
      compared with all lesions: 0.80 (CI 95%: 0.65-0.89) versus 0.69 (CI 95%: 0.54
      0.80), respectively. The overall concordance rate between the 2 readers of LE was
      97.9%. CONCLUSION: Response assessment of liver metastases treated by SBRT can be
      improved by including LE. This study demonstrates the diagnostic and predictive
      utility of LE for assessing local progression at a size still eligible for local
      salvage treatment.

PMID- 25968827
TI  - Non-Rhabdomyosarcoma Soft Tissue Sarcomas in Children: A Surveillance,
      Epidemiology, and End Results Analysis Validating COG Risk Stratifications.
AB  - PURPOSE: Non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) are a heterogeneous
      group of sarcomas that encompass over 35 histologies. With an incidence of ~500
      cases per year in the United States in those <20 years of age, NRSTS are rare and
      therefore difficult to study in pediatric populations. We used the large
      Surveillance, Epidemiology, and End Results (SEER) database to validate the
      prognostic ability of the Children's Oncology Group (COG) risk classification
      system and to define patient, tumor, and treatment characteristics. METHODS AND
      MATERIALS: From SEER data from 1988 to 2007, we identified patients <=18 years of
      age with NRSTS. Data for age, sex, year of diagnosis, race, registry, histology,
      grade, primary size, primary site, stage, radiation therapy, and survival
      outcomes were analyzed. Patients with nonmetastatic grossly resected low-grade
      tumors of any size or high-grade tumors <=5 cm were considered low risk. Cases of
      nonmetastatic tumors that were high grade, >5 cm, or unresectable were considered
      intermediate risk. Patients with nodal or distant metastases were considered high
      risk. RESULTS: A total of 941 patients met the review criteria. On univariate
      analysis, black race, malignant peripheral nerve sheath (MPNST) histology, tumors
      >5 cm, nonextremity primary, lymph node involvement, radiation therapy, and
      higher risk group were associated with significantly worse overall survival (OS)
      and cancer-specific survival (CSS). On multivariate analysis, MPNST histology,
      chemotherapy-resistant histology, and higher risk group were significantly poor
      prognostic factors for OS and CSS. Compared to low-risk patients, intermediate
      patients showed poorer OS (hazard ratio [HR]: 6.08, 95% confidence interval [CI]:
      3.53-10.47, P<.001) and CSS (HR: 6.27; 95% CI: 3.44-11.43, P<.001), and high-risk
      patients had the worst OS (HR: 13.35, 95% CI: 8.18-21.76, P<.001) and CSS (HR:
      14.65, 95% CI: 8.49-25.28, P<.001). CONCLUSIONS: The current COG risk group
      stratification for children with NRSTS has been validated with a large number of
      children in the SEER database.

PMID- 25968828
TI  - In reply to Xie et al.

PMID- 25968829
TI  - In regard to Vargo et al.

PMID- 25968826
TI  - Adding Erlotinib to Chemoradiation Improves Overall Survival but Not Progression
      Free Survival in Stage III Non-Small Cell Lung Cancer.
AB  - PURPOSE: To test, in a single-arm, prospective, phase 2 trial, whether adding the
      epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to
      concurrent chemoradiotherapy for previously untreated, locally advanced,
      inoperable non-small cell lung cancer would improve survival and disease control
      without increasing toxicity. METHODS AND MATERIALS: Forty-eight patients with
      previously untreated non-small cell lung cancer received intensity modulated
      radiation therapy (63 Gy/35 fractions) on Monday through Friday, with
      chemotherapy (paclitaxel 45 mg/m2, carboplatin area under the curve [AUC] = 2) on
      Mondays, for 7 weeks. All patients also received the EGFR tyrosine kinase
      inhibitor erlotinib (150 mg orally 1/d) on Tuesday-Sunday for 7 weeks, followed
      by consolidation paclitaxel-carboplatin. The primary endpoint was time to
      progression; secondary endpoints were overall survival (OS), toxicity, response,
      and disease control and whether any endpoint differed by EGFR mutation status.
      RESULTS: Of 46 patients evaluable for response, 40 were former or never-smokers,
      and 41 were evaluable for EGFR mutations (37 wild-type [WT] and 4 mutated [all
      adenocarcinoma]). Median time to progression was 14.0 months and did not differ
      by EGFR status. Toxicity was acceptable (no grade 5, 1 grade 4, 11 grade 3).
      Twelve patients (26%) had complete responses (10 WT, 2 mutated), 27 (59%) partial
      (21 WT, 2 mutated, 4 unknown), and 7 (15%) none (6 WT, 2 mutated, 1 unknown)
      (P=.610). At 37.0 months' follow-up (range, 3.6-76.5 months) for all patients,
      median OS time was 36.5 months, and 1-, 2-, and 5-year OS rates were 82.6%,
      67.4%, and 35.9%, respectively; none differed by mutation status. Twelve patients
      had no progression, and 34 had local and/or distant failure. Eleven of 27 distant
      failures were in the brain (7 WT, 3 mutated, 1 unknown). CONCLUSIONS: Toxicity
      and OS were promising, but time to progression did not meet expectations. The
      prevalence of distant failures underscores the need for effective systemic
      therapy.

PMID- 25968832
TI  - Cigarette Smoke Modulates NOD1 Signal Pathway and Human beta Defensins Expression
      in Human Oral Mucosa.
AB  - BACKGROUND/AIMS: Nucleotide binding oligomerization domain 1 (NOD1) signal
      pathway and human beta defensins (hBDs) play crucial roles in innate immune.
      Cigarette smoke has been confirmed to dampen innate immune in some human tissues,
      such as oral mucosa. The aim of this study was to evaluate potential effects of
      smoking on NOD1 signaling and hBDs expression in oral mucosa. METHODS: Tissue
      specimens of normal oral mucosa were collected from donors undergoing routine
      surgical treatment. All 20 participants were classified equally as two groups:
      non-smokers and smokers. By using Western blotting and immunohistochemistry, we
      investigated differential expression of crucial molecules in NOD1 signal pathway,
      hBD-1, -2, and -3 in oral mucosa tissues between non-smokers and smokers.
      Immortalized human oral mucosal epithelial (Leuk-1) cells were treated with
      various concentrations of cigarette smoke extract (CSE) for 24h. Western blotting
      and immunofluorescence assays were performed to study CSE-induced alteration of
      protein expression. Leuk-1 cells were treated with 4% CSE, iE-DAP (NOD1 agonist),
      CSE + iE-DAP, BAY 11-7082 (NF-kappaB inhibitor), 4% CSE + BAY 11-7082,
      respectively. Real-time PCR and ELISA were performed to detect the mRNA levels
      and secretion of hBD-1, -2, and -3, respectively. RESULTS: The levels of NOD1, NF
      kappaB, hBD-1 and hBD-3 significantly reduced in oral mucosa tissues of smokers
      compared with non-smokers. The levels of RIP2 (receptor-interacting protein 2),
      phospho-NF-kappaB (P-NF-kappaB) and hBD-2 remarkably enhanced in oral mucosal
      tissues of smokers. CSE treatment suppressed NOD1 and NF-kappaB expression and
      activated RIP2 and P-NF-kappaB expression in Leuk-1 cells. The mRNA and secretory
      levels of hBD-1 and -3 were down-regulated by CSE, while the mRNA and secretory
      level of hBD-2 were up-regulated by CSE. The iE-DAP or BAY 11-7082 treatment
      reversed the regulatory effects of CSE on levels of hBDs. CONCLUSION: The present
      study indicated that cigarette smoke could potentially modulate the expression of
      crucial molecules of NOD1 signal pathway and hBDs in human oral mucosal
      epithelium. NOD1 signal pathway could play an important role in the regulatory
      effects of CSE on hBDs levels in oral mucosal epithelial cells.

PMID- 25968833
TI  - Women's Health Initiative estrogen plus progestin clinical trial: a study that
      does not allow establishing relevant clinical risks.
AB  - OBJECTIVE: This study aims to determine time differences (differences in
      restricted mean survival times [RMSTs]) in the onset of invasive breast cancer,
      coronary heart disease, stroke, pulmonary embolism, colorectal cancer, and hip
      fracture between the placebo group and the conjugated equine estrogens 0.625 mg
      plus medroxyprogesterone acetate 2.5 mg group of the Women's Health Initiative
      (WHI) trial based on survival curves of the original report and to provide
      adequate interpretation of the clinical effects of a given intervention. METHODS:
      Distribution of survival function was obtained from cumulative hazard plots of
      the WHI report; Monte Carlo simulation was performed to obtain censored
      observations for each outcome, in which assumptions of the Cox model were
      evaluated once corresponding hazard ratios had been estimated. Using estimation
      methods such as numerical integration, pseudovalues, and flexible parametric
      modeling, we determined differences in RMSTs for each outcome. RESULTS: Obtained
      cumulative hazard plots, hazard ratios, and outcome rates from the simulated
      model did not show differences in relation to the original WHI report. The
      differences in RMST between placebo and conjugated equine estrogens 0.625 mg plus
      medroxyprogesterone acetate 2.5 mg (in flexible parametric modeling) were 1.17
      days (95% CI, -2.25 to 4.59) for invasive breast cancer, 7.50 days (95% CI, 2.90
      to 12.11) for coronary heart disease, 2.75 days (95% CI, -0.84 to 6.34) for
      stroke, 4.23 days (95% CI, 1.82 to 6.64) for pulmonary embolism, -2.73 days (95%
      CI, -5.32 to -0.13) for colorectal cancer, and -2.77 days (95% CI, -5.44 to -0.1)
      for hip fracture. CONCLUSIONS: The differences in RMST for the outcomes of the
      WHI study are too small to establish clinical risks related to hormone therapy
      use.

PMID- 25968834
TI  - Association of hormone therapy and incident gout: population-based case-control
      study.
AB  - OBJECTIVE: This study aims to assess the odds of developing incident gout in
      association with the use of postmenopausal estrogen-progestogen therapy,
      according to type, timing, duration, and route of administration of estrogen
      progestogen therapy. METHODS: We conducted a retrospective population-based case
      control analysis using the United Kingdom-based Clinical Practice Research
      Datalink. We identified women (aged 45 y or older) who had a first-time diagnosis
      of gout recorded between 1990 and 2010. We matched one female control with each
      case on age, general practice, calendar time, and years of active history in the
      database. We used multivariate conditional logistic regression to calculate odds
      ratios (ORs) with 95% CIs (adjusted for confounders). RESULTS: The adjusted OR
      for gout with current use of oral formulations of opposed estrogens (estrogen
      progestogen) was 0.69 (95% CI, 0.56-0.86) compared with never use. Current use
      was associated with a decreased OR for gout in women without renal failure
      (adjusted OR, 0.71; 95% CI, 0.57-0.87) and hypertension (adjusted OR, 0.62; 95%
      CI, 0.44-0.87) compared with never use. Tibolone was associated with a decreased
      OR for gout (adjusted OR, 0.77; 95% CI, 0.63-0.95) compared with never use.
      Estrogens alone did not alter the OR for gout. CONCLUSIONS: Current use of oral
      opposed estrogens, but not unopposed estrogens, is associated with a decreased OR
      for incident gout in women without renal failure and is more pronounced in women
      with hypertension. Use of tibolone is associated with a decreased OR for incident
      gout. The decreased OR for gout may be related to the progestogen component
      rather than the estrogen component.

PMID- 25968835
TI  - Bone mineral density measurements: how often should bone mineral density be
      measured in postmenopausal women? Results from the Women's Health Initiative
      study.

PMID- 25968836
TI  - Lack of effect of intravaginal dehydroepiandrosterone (DHEA, prasterone) on the
      endometrium in postmenopausal women.
AB  - OBJECTIVE: This study aims to evaluate the effects of intravaginal
      dehydroepiandrosterone (DHEA, prasterone) on the endometrium in postmenopausal
      women. METHODS: Intravaginal DHEA (6.5 mg) was administered daily for 52 weeks to
      422 women who had endometrial biopsy at baseline and end of study, whereas 15
      women were similarly treated for 26 to 52 weeks. Participants in three other
      studies received 3.25 mg (n = 126), 6.5 mg (n = 129), or 13 mg (n = 30) of DHEA
      for 12 weeks; women similarly had baseline and end-of-study biopsies. Endometrial
      biopsy samples were available for 668 women at baseline and end of study, with
      sufficient material for analysis. RESULTS: Endometrial atrophy or inactive
      endometrium (668 women) was found in all women treated with intravaginal DHEA.
      Similar atrophy was observed in 119 of 121 participants with sufficient material
      for analysis who received placebo. CONCLUSIONS: After cessation of estradiol
      secretion by the ovaries at menopause, the estrogens made by mechanisms of
      intracrinology are inactivated intracellularly at their site of formation and
      action, thus maintaining serum estradiol at biologically inactive concentrations
      to avoid stimulation of the endometrium. The absence of enzymes that are able to
      transform DHEA into estrogens in the endometrium explains the typical endometrial
      atrophy in all normal postmenopausal women in the presence of variable
      concentrations of circulating endogenous DHEA. According to these mechanisms, the
      inactive sex steroid precursor DHEA administered intravaginally acts exclusively
      in the vagina, whereas all serum sex steroids remain well within the biologically
      inactive postmenopausal reference range, thus avoiding any stimulation of the
      already atrophic endometrium.

PMID- 25968837
TI  - The mechanism of ligand-induced activation or inhibition of MU- and kappa-opioid
      receptors.
AB  - G-protein-coupled receptors (GPCRs) are important targets for treating severe
      diseases. However why certain molecules act as activators whereas others, with
      similar structures, block GPCR activation, is poorly understood since the same
      molecule can activate one receptor subtype while blocking another closely related
      receptor. To shed light on these central questions, we used all-atom, long-time
      scale molecular dynamics simulations on the kappa-opioid and MU-opioid receptors
      (kappaOR and MUOR). We found that water molecules penetrating into the receptor
      interior mediate the activating versus blocking effects of a particular ligand
      receptor interaction. Both the size and the flexibility of the bound ligand
      regulated water influx into the receptor. The solvent-accessible inner surface
      area was found to be a parameter that can help predict the function of the bound
      ligand. 

PMID- 25968838
TI  - p53 gene therapy-based transarterial chemoembolization for unresectable
      hepatocellular carcinoma: A prospective cohort study.
AB  - BACKGROUND AND AIM: Transarterial chemoembolization (TACE) is used for treating
      unresectable hepatocellular carcinoma (HCC), but its efficacy still needs to be
      improved. Recombinant adenovirus p53 (rAd-p53) injection is a gene therapeutic
      agent that could improve the prognosis of HCC patients. This study aimed to
      evaluate the efficacy and safety of rAd-p53-based TACE for treating unresectable
      HCC. METHODS: Prospective analysis of patients who received rAd-p53-based TACE or
      TACE alone in Chongqing Cancer Institute from January 1, 2011 to December 31,
      2012. The primary endpoint is overall survival. The secondary endpoints were
      progression-free survival, response rate, and safety. RESULTS: One hundred two
      patients were enrolled in this study. Forty-nine patients received the rAd-p53
      based TACE, and 53 patients received TACE alone. The rAd-p53-based TACE treatment
      strategy improved the overall survival (hazard ratio: 0.58, 95% confidence
      interval: 0.35-0.96, P = 0.035), progression-free survival (hazard ratio: 0.60,
      95% confidence interval: 0.37-0.97, P = 0.037), response rate (P = 0.047)
      compared with TACE monotherapy. The rAd-p53-based TACE treatment group caused
      more occurrences of fever than with TACE alone (P = 0.01). However, symptomatic
      treatment may solve this problem. CONCLUSIONS: rAd-p53-based TACE treatment
      strategy is effective and safe for treating unresectable HCC. Large-scale
      randomized clinical trials are needed to verify these results.

PMID- 25968839
TI  - ACSM Clinician Profile.

PMID- 25968840
TI  - Self-talk, deception, and placebo power in sports performance.

PMID- 25968842
TI  - Triathlon swim deaths.

PMID- 25968843
TI  - The National Youth Sports Health & Safety Institute: a healthy and sustainable
      approach to youth sports.

PMID- 25968844
TI  - Overtraining syndrome.

PMID- 25968845
TI  - Detection and prevention of glenohumeral epiphysiolysis.

PMID- 25968846
TI  - Medical planning for very large events: Special Olympics World Games Los Angeles
      2015.
AB  - Mass gathering events that involve special populations have challenges that
      require unique medical planning. The key to a successful mass event is in the
      preparation, planning, and communication. Concerns in communication such as
      language barriers, age of participants, and intellectual disability should be
      addressed early in the planning. In the event of a mass casualty disaster, there
      should be a clear chain of command and escalation policy. The primary concern of
      the sports medicine team is to ensure safety for the participation of an athlete.
      The risk of injury to an athlete varies depending on the event and venue. The
      sporting venue may require special consideration for access to athletes, crowd
      control, and ingress/egress of medical personnel and transports. In order to
      ensure safety and efficient care, it is paramount to have the necessary medical
      planning and preparedness to manage a large-scale sporting event.

PMID- 25968847
TI  - The special olympics healthy athletes experience.
AB  - Special Olympics is the largest sports organization in the world serving athletes
      with intellectual disabilities. Because of their unique needs, Special Olympics
      has designed a multitude of programs specifically for athletes with intellectual
      disabilities, including the world's largest public health screening program for
      people with intellectual disabilities, known as the Special Olympics Healthy
      Athletes Program. This article describes the Healthy Athletes program and some of
      the results of the program within the context of impacting health care
      professional education with respect to athletes with intellectual disabilities. 

PMID- 25968848
TI  - Unexpected disasters at organized sporting events: considerations in preparation
      and response.
AB  - Preparing for the unexpected or unusual occurrence is always a challenge. When
      you add large collections of athletes and spectators, that challenge is certainly
      magnified, and proper planning and preparation are even more critical in reducing
      the damage done. The aim of this article is to stimulate thought toward preparing
      the medical director and staff in being ready to respond to the unexpected
      disaster at a sporting event. 

PMID- 25968849
TI  - Mass screenings at mass participation events: MedFest at Special Olympics.
AB  - MedFest events offer preparticipation physical evaluations to Special Olympics
      athletes. This free service can occur as free-standing events or can take place
      during Special Olympics Games. The goals of MedFest are to screen for conditions
      that are potentially life threatening or disabling or may predispose the athlete
      to injury or illness. The medication, cardiac, and neurologic histories are
      essential components of the evaluation. The majority of athletes screened during
      a MedFest event will be cleared for sports participation, but many will require
      some type of referral for further care. It is important for the organizers of the
      MedFest to have prearranged protocols to ensure that the athletes efficiently
      receive the required evaluations. 

PMID- 25968850
TI  - On-site management of medical encounters during obstacle adventure course
      participation.
AB  - Obstacle adventure courses (OAC) are increasing in popularity. Although injuries
      are not uncommon, there is scant medical literature documenting the morbidity and
      mortality associated with these events. This manuscript describes a case series.
      Event demographics, medical coverage, and injuries/illnesses documented during
      four OAC events in British Columbia, Canada, are discussed - Tough MudderTM (2012
      and 2013) and Warrior Dash(c) (2011 and 2012). The patient presentation rate
      across all events ranged from 26.53 to 37.40 per 1,000 participants. Ambulance
      transfer rates were low (range = 0 to 5 per event day, 0% to 1.1% of patients
      seen). Although some illness presentations and injuries required a higher level
      of care, the majority of medical issues were related to musculoskeletal injuries
      of the lower limbs. Advanced knowledge about risks and patient presentations
      associated with participation in OAC may influence on-site staffing, deployment
      patterns, rescue equipment, and transfer to hospital planning for diagnostic
      imaging and definitive treatment.

PMID- 25968851
TI  - Differences between family and emergency medicine training before sports medicine
      fellowship.
AB  - Residency training clearly impacts physicians' approach toward fellowship in
      Primary Care Sports Medicine. Although the Accreditation Council for Graduate
      Medical Education sets strict standards for all programs, family medicine and
      emergency medicine training differ a great deal in general and provide physicians
      from both backgrounds varied perspectives and skill sets. The family physician
      acquires a substantial amount of experience in continuity of care and integration
      of health care into a patient's everyday life. On the other hand, the emergency
      physician receives exceptional training in the management of acutely ill and
      injured patients and leadership of a large health care team. Furthermore, while
      the emergency physician may be skilled in procedures such as fracture reduction
      and diagnostic ultrasound, the family physician is proficient in developing
      patient rapport and compliance with a treatment plan. Although physicians from
      different backgrounds may start with many differences, fellowship training is
      essential in bridging those gaps.

PMID- 25968853
TI  - Is self myofascial release an effective preexercise and recovery strategy? A
      literature review.
AB  - The use of self myofascial release (SMR) via a foam roller or roller massager is
      becoming increasingly popular both to aid recovery from exercise and prevent
      injury. Our objective was to review the literature on SMR and its use for
      preexercise, recovery, or maintenance. PUBMED, EBSCO (MEDLINE), EMBASE, and
      CINAHL were searched for variations and synonyms of "self myofascial release" and
      "foam rolling." Data from nine studies were examined, and overall quality varied
      based on study protocol, muscle group targeted, and outcomes measured. Despite
      the heterogeneity of these studies, SMR appears to have a positive effect on
      range of motion and soreness/fatigue following exercise, but further study is
      needed to define optimal parameters (timing and duration of use) to aid
      performance and recovery.

PMID- 25968854
TI  - Overuse throwing injuries in skeletally immature athletes--diagnosis, treatment,
      and prevention.
AB  - The number of skeletally immature athletes participating in organized sport is
      near an all-time high. For nearly half a century, the medical community has
      investigated the link between shoulder and elbow injuries with repetitive
      throwing. Despite substantial literature and research, several controversies
      still exist, including when to begin throwing breaking pitches. Furthermore,
      despite introduction of pitch recommendations for youth baseball, misconceptions,
      poor understanding of, and adherence to these guidelines persist. High-velocity
      and high-volume throwing and throwing while fatigued are significant risk factors
      for injury. Improved awareness and adherence to throwing guidelines should limit
      the number of injuries. Proper identification and treatment of injuries when they
      do occur can allow our skeletally immature athletes to safely return to overhead
      sports activities. 

PMID- 25968852
TI  - Effect of neurocognition and concussion on musculoskeletal injury risk.
AB  - Research regarding musculoskeletal injury risk has focused primarily on
      anatomical, neuromuscular, hormonal, and environmental risk factors; however,
      subsequent injury risk screening and intervention programs have been largely
      limited to neuromuscular factors and have faced challenges in both implementation
      and efficacy. Recent studies indicate that poor neurocognitive performance,
      either at baseline or in the aftermath of a concussion, is associated with
      elevated risk of musculoskeletal injury. Despite the relatively limited current
      understanding regarding the nature of the relationship between different aspects
      of neurocognitive performance and musculoskeletal injury risk, this is a
      promising area of research that may yield significant advances in musculoskeletal
      injury risk stratification, rehabilitation, and prevention.

PMID- 25968855
TI  - Lateral epicondylosis: emerging management options.
AB  - Lateral epicondylosis is one of the most prevalent disorders of the arm and
      results in significantly decreased function among the workforce and athletes.
      Historically, the disorder has been diagnosed clinically and treated as an
      inflammatory entity. Management strategies have included anti-inflammatory
      medications and techniques, including oral nonsteroidal anti-inflammatories,
      injected corticosteroid, and physical therapy with modalities. More recent
      literature postulates a degenerative or compressive etiology, directing some
      clinicians to try new, more regenerative management strategies such as platelet
      rich plasma and stem cell injections. To date, literature evaluating these new
      treatment methods has shown positive results, although no definitive conclusions
      can be drawn. More research is needed to evaluate these new treatment methods,
      and a new look at the diagnosis of the disorder with ultrasound imaging may be
      reasonable to consider. 

PMID- 25968856
TI  - Resistance exercise: how much is enough?
AB  - Multiple organizations recommend that resistance exercise be part of an adult
      health and fitness regimen. Extensive research has been done over the years on
      how to appropriately use a resistance exercise program to increase strength and
      power for general health and improve athletic performance. This article will
      review the literature on the components of a resistance exercise program and the
      recommendations for increasing strength and power in healthy adults. 

PMID- 25968857
TI  - Basic recovery aids: what's the evidence?
AB  - This review summarizes the evidence base for using compression, massage, caloric
      replacement, cold, and heat as exercise recovery aids in sport. 

PMID- 25968859
TI  - Depression in athletes or increased depressive symptoms in athletes?

PMID- 25968858
TI  - Training the developing brain part II: cognitive considerations for youth
      instruction and feedback.
AB  - Growing numbers of youth participating in competitive, organized physical
      activity have led to a concern for the risk of sports-related injuries during
      important periods of human development. Recent studies have demonstrated the
      ability of integrative neuromuscular training (INT) to enhance athletic
      performance and reduce the risk of sports-related injuries in youth. Successful
      implementation of INT necessitates instruction from knowledgeable and qualified
      instructors who understand the unique physical, cognitive, and psychosocial
      characteristics of the youth to provide appropriate training instruction and
      feedback. Principles of a classical theory of cognitive development provide a
      useful context for discussion of developmentally appropriate methods and
      strategies for INT instruction of youth. INT programs that consider these
      developmentally appropriate approaches will provide a controlled efficacious
      environment for youth to improve athletic performance and reduce risk of sports
      related injury, thus promoting a healthy active lifestyle beyond an individual's
      formative years.

PMID- 25968860
TI  - Response to the letter to the editor.

PMID- 25968861
TI  - The cardiovascular Preparticipation Evaluation (PPE) for the primary care and
      sports medicine physician, Part I.

PMID- 25968862
TI  - History and application of the AHA 12 points for assessing cardiovascular risk in
      athletes.

PMID- 25968863
TI  - Chest pain in athletes from personal history section (medical causes).

PMID- 25968864
TI  - Chest pain in athletes from personal history section (musculoskeletal causes).

PMID- 25968865
TI  - Syncope in athletes of cardiac origin: 2B. From personal history and physical
      examination sections.

PMID- 25968866
TI  - Syncope in athletes of neurological origin: 2B. From personal history and
      physical examination sections.

PMID- 25968867
TI  - 3A. Personal history: Have you ever had excessive shortness of breath or fatigue
      with exercise beyond what is expected for your level of fitness?

PMID- 25968868
TI  - 3B. Personal history: Have you ever had excessive shortness of breath or fatigue
      with exercise beyond what is expected for your level of fitness?

PMID- 25968869
TI  - Heart murmurs in athletes: from personal history and physical examination
      sections.

PMID- 25968870
TI  - Heart murmur and physical examination in athletes with a focus on congenital
      heart disease.

PMID- 25968871
TI  - Hypertension in athletes from physical examination and personal history section.

PMID- 25968872
TI  - Oil-in-Water Emulsion Exhibits Bitterness-Suppressing Effects in a Sensory
      Threshold Study.
AB  - Little is known about how emulsion characteristics affect saltiness/bitterness
      perception. Sensory detection and recognition thresholds of NaCl, caffeine, and
      KCl in aqueous solution compared with oil-in-water emulsion systems were
      evaluated. For emulsions, NaCl, KCl, or caffeine were dissolved in water +
      emulsifier and mixed with canola oil (20% by weight). Two emulsions were
      prepared: emulsion 1 (viscosity = 257 cP) and emulsion 2 (viscosity = 59 cP). The
      forced-choice ascending concentration series method of limits (ASTM E-679-04) was
      used to determine detection and/or recognition thresholds at 25  degrees C. Group
      best estimate threshold (GBET) geometric means were expressed as g/100 mL.
      Comparing NaCl with KCl, there were no significant differences in detection GBET
      values for all systems (0.0197 - 0.0354). For saltiness recognition thresholds,
      KCl GBET values were higher compared with NaCl GBET (0.0822 - 0.1070 compared
      with 0.0471 - 0.0501). For NaCl and KCl, emulsion 1 and/or emulsion 2 did not
      significantly affect the saltiness recognition threshold compared with that of
      the aqueous solution. However, the bitterness recognition thresholds of caffeine
      and KCl in solution were significantly lower than in the emulsions (0.0242 -
      0.0586 compared with 0.0754 - 0.1025). Gender generally had a marginal effect on
      threshold values. This study showed that, compared with the aqueous solutions,
      emulsions did not significantly affect the saltiness recognition threshold of
      NaCl and KCl, but exhibited bitterness-suppressing effects on KCl and/or
      caffeine. 

PMID- 25968874
TI  - Clinical Significance of miR-1826 as a Novel Prognostic Biomarker in Colorectal
      Cancer.
AB  - Several reports indicated that aberrant miR-1826 was involved in the initiation
      and progression of malignancies. However, the clinical significance of miR-1826
      in human colorectal cancer (CRC) has not been addressed. The aim of this study
      was to evaluate the expression and clinical significance of miR-1826 in CRC. We
      detected miR-1826 expressions by quantitative real.time PCR (qRT-PCR) in 72 CRC
      tissues, adjacent non.tumor tissues (NATs) and five CRC cell lines, and found
      that miR-1826 expression in CRC tissues was higher than that in NATs (p<0.05).
      High miR-1826 expression was significantly associated with some clinicopathologic
      features such as regional lymph node metastasis (p=0.018), advanced TNM clinical
      stage (p=0.004), which led to a poor overall survival rate in CRC patients
      (p=0.032). Our further studies in vitro also demonstrated that miR-1826 inhibitor
      could effectively suppress the cell proliferation, promote apoptosis and induce
      G0/G1 cell cycle arrest in CRC cells (p<0.05). Meanwhile, the abilities of cell
      invasion and migration were effectively suppressed by miR-1826 inhibitor
      (p<0.05). These findings strongly suggested that miR-1826 played a critical role
      in the initiation and progression of CRC. Up-regulation of miR-1826 might serve
      as a novel prognostic marker of CRC and could be a potential target for CRC
      therapies.

PMID- 25968875
TI  - miRNA-101 Suppresses Epithelial-to-Mesenchymal Transition by Targeting HMGA2 in
      Pancreatic Cancer Cells.
AB  - miR-101 is an outstanding tumor suppressor in various cancers, while its role in
      pancreatic cancer (PC) is still unknown. The aim of this study was to investigate
      the role of miR-101 in epithelial-to-mesenchymal transition (EMT) and its
      clinical relevance in PC. Our data showed that the miR-101 expression was
      significantly decreased in human PC tissues, compared to non-tumor counterparts
      (p<0.05), which was reversely correlated to clinical characteristics, including
      lymph node metastasis, more venous infiltration, higher expression of CA19-9 and
      TNM stage (p<0.05). Low miR-101 expression was also confirmed to be associated
      with a poorer overall survival rate in PC patients (p<0.05). We identified high
      mobility group AT-hook 2 (HMGA2) gene as a putative target of miR-101 in PC by
      bioinformatics analysis, dual luciferase activity and western blot assay, and
      found that miR-101 could specifically target the HMGA2 3'-untranslated region (3'
      UTR) (p<0.05). Knockdown of HMGA2 reversed EMT resembling that of miR-101 over
      expression. An inverse correlation between miR-101 and HMGA2 was observed in
      patients with PC (p<0.05). Taken together, our findings speculated that miR-101
      might act as an inhibiting factor in EMT process in PC and up-regulation of miR
      101 might be considered as a potentially key molecular treatment strategy for PC
      patients. 

PMID- 25968876
TI  - Pseudogene PTENP1 Suppresses Gastric Cancer Progression by Modulating PTEN.
AB  - PTENP1 has been demonstrated to function as a tumor suppressor in several cancer
      cells. However, its expression and biological roles in gastric cancer (GC) have
      not yet been investigated. In this study, we demonstrated that PTENP1 was
      frequently decreased in GC tissues and cell lines, which might be partly
      associated with DNA hypermethylation, and lower PTENP1 expression was associated
      with larger tumor size, more advanced stage, deeper invasion depth and lymphatic
      metastasis. In addition, our data suggested that PTENP1 could regulate GC cell
      proliferation, apoptosis, migration and invasion in vitro. Furthermore, we
      demonstrated that PTENP1 could modulate the PTEN protein expression. Taken
      together, these results suggest that PTENP1 functions as a novel tumor suppressor
      in GC and its suppressive ability may be involved in the modulation of PTEN. 

PMID- 25968877
TI  - Prognostic Value and Clinicopathological Differences of Bmi1 in Gastric Cancer: A
      Meta-analysis.
AB  - B cell-specific Moloney murine leukemia virus integration site 1 (Bmi1) was
      identified as a biomarker of cancer stem cells, and over-expression of Bmi1 might
      enhance tumor aggressive clinical behavior in gastric cancer (GC). Our aim of
      this meta-analysis is to investigate the prognostic role and clinicopathological
      differences of Bmi1 in GC patients. A total of 6 studies up to September 2014
      were included in our study. Our results showed that there were no relationships
      between Bmi1 expression and the gender (pooled OR=0.87, 95%CI=0.66-1.14, P=0.319,
      fixed effect), age (pooled OR=1.22, 95%CI=0.95-1.59, P=0.126, fixed effect) and
      differentiation (pooled OR=1.15, 95%CI=0.71-1.86, P=0.582, random effect) in GC
      patients. But high Bmi1 expression was significantly correlated with the clinical
      stage (pooled OR=3.04, 95%CI=1.31-7.07, P=0.010, random effect), tumor size
      (pooled OR=2.01, 95%CI=1.14-3.55, P=0.016, random effect), T classification
      (pooled OR=2.79, 95%CI=1.94-4.03, P<0.001, fixed effect), lymph node metastasis
      (pooled OR=2.24, 95%CI=1.47-3.39, P<0.001, random effect) and distant metastasis
      (pooled OR=5.05, 95%CI=1.29-19.70, P=0.020, random effect), and led to a poor
      overall survival (OS) in GC patients (RR=3.38, 95%CI=2.43-4.69, P<0.001, fixed
      effect). These findings suggested that Bmi1 might serve as a novel and effective
      prognostic biomarker in GC, and could be a promising emerging molecular target in
      GC therapy. 

PMID- 25968878
TI  - Addition of a UL5 helicase-primase subunit point mutation eliminates bursal
      thymic atrophy of Marek's disease virus ?Meq recombinant virus but reduces
      vaccinal protection.
AB  - Marek's disease virus (MDV) is an oncogenic alphaherpesvirus and the causative
      agent of Marek's disease (MD), characterized by immunosuppression, paralysis,
      nerve enlargement and induction of T-cell lymphomas in chickens. Despite
      widespread usage of vaccines since the 1970s to control MD, more virulent field
      strains of MDV have emerged that overcome vaccinal protection, necessitating the
      development of new and more protective MD vaccines. The ?Meq virus, a recombinant
      Md5 strain MDV lacking the viral oncogene Meq, is one candidate MD vaccine with
      great potential but unfortunately it also causes bursal-thymic atrophy (BTA) in
      maternal antibody negative chickens, raising concerns that impede commercial use
      as a vaccine. Previously, we identified a point mutation within UL5 that reduced
      in vivo replication in attenuated viruses. We proposed that introduction of the
      UL5 point mutation into the ?Meq virus would reduce in vivo replication and
      eliminate BTA yet potentially retain high protective abilities. In birds, the
      ?Meq+UL5 recombinant MDV had reduced replication compared to the original ?Meq
      virus, while weights of lymphoid organs indicated that ?Meq+UL5 did not induce
      BTA, supporting the hypothesis that reduction of in vivo replication would also
      abolish BTA. Vaccine trials of the ?Meq+UL5 virus compared to other ?Meq-based
      viruses and commercial vaccines show that, while the ?Meq+UL5 does provide
      vaccinal protection, this protection was also reduced compared to the original
      ?Meq virus. Therefore, it appears that a very delicate balance is required
      between levels of replication able to induce high vaccinal protection, yet not so
      high as to induce BTA. 

PMID- 25968879
TI  - Acute One-Stop Cardiovascular Magnetic Resonance Imaging for Differential
      Diagnosis in Patients with Acute Coronary Syndrome and Unobstructed Coronary
      Arteries.
AB  - OBJECTIVE: We aimed to evaluate the contributions of acute one-stop
      cardiovascular magnetic resonance (CMR) imaging to the differential diagnosis of
      acute coronary syndrome (ACS) and unobstructed coronary arteries. SUBJECTS AND
      METHODS: In this study, 32 consecutive patients who presented with ACS and
      unobstructed coronary arteries on angiography were enrolled between January 2010
      and December 2012. Acute one-stop CMR, including cine, angiography, black-blood,
      first-pass perfusion and late gadolinium enhancement (LGE) imaging, was performed
      with a pre-specified algorithm which was decided on by the doctors for all
      patients. The intimal flap in the aorta and the filling defect in the pulmonary
      artery were detected on MR angiography imaging. Left ventricular wall motion and
      ventricular thickness were analyzed in cine-mode sequences. The LGE images were
      reviewed for the presence, anatomical distribution and extent of contrast
      enhancement. RESULTS: The acute one-stop CMR study was completed in all the 32
      patients without adverse events. The overall time duration was between 15 and 60
      min. Of the 32 patients, a CMR diagnosis was made in 30 (93.8%). Aortic
      dissection was detected in 3 patients, pulmonary embolism in 2, hypertrophic
      cardiomyopathy in 2, acute myocardial infarction in 5, acute myocarditis in 16
      and stress cardiomyopathy in 2. No confirmed diagnosis was established in the
      remaining 2 patients with normal CMR. CONCLUSION: Acute one-stop CMR allowed for
      the identification of an aetiology in most of the patients in this study. It may
      prove to be of immense help in establishing a differential diagnosis in patients
      presenting with acute chest pain, elevated troponin I and normal coronary
      arteries.

PMID- 25968880
TI  - The impact of interchain hydrogen bonding on beta-hairpin stability is readily
      predicted by molecular dynamics simulation.
AB  - Peptides are frequently used model systems for protein folding. They are also
      gaining increased importance as therapeutics. Here, the ability of molecular
      dynamics (MD) simulation for describing the structure and dynamics of beta
      hairpin peptides was investigated, with special attention given to the impact of
      a single interstrand sidechain to sidechain interaction. The MD trajectories were
      compared to structural information gained from solution NMR. By assigning frames
      from restraint-free MD simulations to an intuitive hydrogen bond on/off pattern,
      folding ratios and folding pathways were predicted. The computed molecular model
      successfully reproduces the folding ratios determined by NMR, indicating that MD
      simulation may be straightforwardly used as a screening tool in beta-hairpin
      design.

PMID- 25968881
TI  - Coupling the Biophysical and Social Dimensions of Wildfire Risk to Improve
      Wildfire Mitigation Planning.
AB  - We describe recent advances in biophysical and social aspects of risk and their
      potential combined contribution to improve mitigation planning on fire-prone
      landscapes. The methods and tools provide an improved method for defining the
      spatial extent of wildfire risk to communities compared to current planning
      processes. They also propose an expanded role for social science to improve
      understanding of community-wide risk perceptions and to predict property owners'
      capacities and willingness to mitigate risk by treating hazardous fuels and
      reducing the susceptibility of dwellings. In particular, we identify spatial
      scale mismatches in wildfire mitigation planning and their potential adverse
      impact on risk mitigation goals. Studies in other fire-prone regions suggest that
      these scale mismatches are widespread and contribute to continued wildfire
      dwelling losses. We discuss how risk perceptions and behavior contribute to scale
      mismatches and how they can be minimized through integrated analyses of landscape
      wildfire transmission and social factors that describe the potential for
      collaboration among landowners and land management agencies. These concepts are
      then used to outline an integrated socioecological planning framework to identify
      optimal strategies for local community risk mitigation and improve landscape
      scale prioritization of fuel management investments by government entities. 

PMID- 25968882
TI  - Development of two novel high-throughput assays to quantify ubiquitylated
      proteins in cell lysates: application to screening of new anti-malarials.
AB  - BACKGROUND: The ubiquitin proteasome system (UPS) is one of the main
      proteolytical pathways in eukaryotic cells and plays an essential role in key
      cellular processes such as cell cycle, stress response, signal transduction, and
      transcriptional regulation. Many components of this pathway have been implicated
      in diverse pathologies including cancer, neurodegeneration and infectious
      diseases, such as malaria. The success of proteasome inhibitors in clinical
      trials underlines the potential of the UPS in drug discovery. METHODS: Plasmodium
      falciparum, the malaria causative pathogen, has been used to develop two assays
      that allow the quantification of the parasite protein ubiquitylation levels in a
      high-throughput format that can be used to find new UPS inhibitors. RESULTS: In
      both assays tandem ubiquitin binding entities (TUBEs), also known as ubiquitin
      traps, have been used to capture ubiquitylated proteins from cell lysates. The
      primary assay is based on AlphaLISA technology, and the orthogonal secondary
      assay relies on a dissociation-enhanced lanthanide fluorescent immunoassay
      (DELFIA) system. A panel of well-known proteasome inhibitors has been used to
      validate both technologies. An excellent correlation was obtained between these
      biochemical assays and the standard whole cell assay that measures parasite
      growth inhibition. CONCLUSIONS: The two assays presented can be used in a high
      throughput format to find new UPS inhibitors for P. falciparum and could help to
      identify new targets within this system. This methodology is also applicable to
      other cellular contexts or pathologies.

PMID- 25968883
TI  - Evaluation of Sexual Function Before and After Hip Arthroscopic Surgery for
      Symptomatic Femoroacetabular Impingement.
AB  - BACKGROUND: It is unknown if chronic hip pain due to femoroacetabular impingement
      (FAI) may cause sexual difficulties. Available evidence suggests that hip
      arthroscopic surgery may be effective for the treatment of symptomatic FAI;
      however, sexual function before and after hip arthroscopic surgery has not been
      reported. PURPOSE/HYPOTHESIS: The purpose of this study was to determine the
      presence and significance of sexual difficulties in patients with chronic hip
      pain due to symptomatic FAI both before and after hip arthroscopic surgery. The
      hypotheses were that (1) chronic hip pain due to symptomatic FAI has a negative
      effect on sexual function, (2) hip arthroscopic surgery improves the level of
      sexual function postoperatively, (3) the characteristics of sexual difficulties
      may be dependent on sex or age, (4) patients lack knowledge of potential sexual
      activity changes in the preoperative and postoperative periods, and (5) patients
      desire a greater level of discussion regarding potential changes in sexual
      function. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A 23-item
      Likert-style questionnaire assessing preoperative and postoperative sexual
      function and a modified Harris Hip Score questionnaire were administered to 305
      consecutive patients who underwent hip arthroscopic surgery for FAI with a
      minimum 1-year follow-up. Comparative analysis was performed between sexes and
      age groups (young: <40 years; old: >40 years). RESULTS: Of 131 respondents,
      preoperative sexual difficulties were reported by 66%, occurring 30.8 +/- 49.1
      days after the onset of FAI symptoms. Primary causes of difficulty included pain
      (77.9%), stiffness (47.1%), and loss of interest (21.4%). Sexual activity resumed
      29.2 +/- 20.1 days postoperatively, while sex with minimal pain occurred at 48.8
      +/- 40.6 days. Female patients and older patients (>40 years old) resumed sexual
      activity later (female: 34.8 +/- 23.2 days; male: 21.0 +/- 10.7 days; P < .0001)
      (young: 26.3 +/- 21.7 days; old: 35.7 +/- 13.5 days; P = .017). The frequency of
      sexual activity increased in 32.3%, decreased in 16.9%, and was unchanged in
      48.5%. Among patients who reported an increase in the frequency of sexual
      activity, there was a greater proportion of male patients and younger patients
      (female: 38.1%; male: 61.9%; P < .0001) (young: 78.6%; old: 21.4%; P < .0001).
      More female patients reported alterations in sexual positioning (female: 82.3%;
      male: 17.7%; P < .0001). To obtain information on sexual function, 77.4% of
      patients preferred a discussion with the surgeon, and 67.4% preferred a booklet
      on the subject. Relief of pain after arthroscopic surgery was experienced by
      88.9%, and only 10.8% reported current sexual difficulties. CONCLUSION: This
      study demonstrates the prevalence of sexual difficulties among the majority of
      patients with symptomatic FAI, the significant effect that these difficulties may
      have on quality of life, and the ability of hip arthroscopic surgery to improve
      sexual function postoperatively. While further studies are required to elucidate
      what specific factors are associated with sexual difficulties, the current study
      suggests that this is an important topic to explore.

PMID- 25968884
TI  - Histological Evaluation of Tendon-Bone Healing of an Anterior Cruciate Ligament
      Hamstring Graft in a 14-Year-Old Boy.

PMID- 25968886
TI  - Type IV dual left anterior descending coronary artery.

PMID- 25968885
TI  - On-pump versus off-pump coronary artery bypass graft surgery among patients with
      type 2 diabetes in the Bypass Angioplasty Revascularization Investigation 2
      Diabetes trial.
AB  - OBJECTIVES: Conclusive evidence is lacking regarding the benefits and risks of
      performing off-pump versus on-pump coronary artery bypass graft (CABG) for
      patients with diabetes. This study aims to compare clinical outcomes after off
      pump and on-pump procedures for patients with diabetes. METHODS: The Bypass
      Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial enrolled
      patients with type 2 diabetes and documented coronary artery disease, 615 of whom
      underwent CABG during the trial. The procedural complications, 30-day outcomes,
      long-term clinical and functional outcomes were compared between the off-pump and
      on-pump groups overall and within a subset of patients matched on propensity
      score. RESULTS: On-pump CABG was performed in 444 (72%) patients, and off-pump
      CABG in 171 (28%). The unadjusted 30-day rate of death/myocardial infarction
      (MI)/stroke was significantly higher after off-pump CABG (7.0 vs 2.9%, P = 0.02)
      despite fewer complications (10.3 vs 20.7%, P = 0.003). The long-term risk of
      death [adjusted hazard ratio (aHR): 1.41, P = 0.2197] and major cardiovascular
      events (death, MI or stroke) (aHR: 1.47, P = 0.1061) did not differ statistically
      between the off-pump and on-pump patients. Within the propensity-matched sample
      (153 pairs), patients who underwent off-pump CABG had a higher risk of the
      composite outcome of death, MI or stroke (aHR: 1.83, P = 0.046); the rates of
      procedural complications and death did not differ significantly, and there were
      no significant differences in the functional outcomes. CONCLUSIONS: Patients with
      diabetes had greater risk of major cardiovascular events long-term after off-pump
      CABG than after on-pump CABG.

PMID- 25968888
TI  - Application of the varying coefficient model to the behaviour risk factor
      surveillance data in Italy: a study of changing smoking prevalence among sub
      populations.
AB  - BACKGROUND: Behaviour risk factor surveillance (BRFS) data can be an important
      source of information for studying changes in various health outcomes and risk
      factors. Results obtained from surveillance data analysis are vital for informing
      health policy interventions, particularly with regards to evolutionary aspects.
      The objective of this analysis was to recommend a method that can be used for
      analysing trends in the association among variables from large public health data
      sets. This was demonstrated by examining the changing effects of various
      covariates, representing different sub-populations, on smoking status over time.
      METHODS: In our work, we propose the use of varying coefficient models (VCM) with
      non-parametric techniques to catch the dynamics of the evolutionary processes
      under study. This is a useful method, which allows coefficients to vary with time
      using smooth functions. Italian BRFS data from 2008-2012 was used with a sample
      size of 185,619 observations. In the application, a time VCM is fit for a smoking
      status binary outcome variable using the P-spline estimation method. The model
      includes ten independent variables comprising socio-demographic, health risk and
      behaviour variables. RESULTS: The VCM fit for the data indicates that the
      coefficients for some of the categories for the age and the alcohol consumption
      variables varied with time. The main results show that Italians aged 18-29 and 40
      49 had higher odds of being smokers compared to those aged 60-69; however, these
      odds significantly decreased in the period 2008-2012. In addition, those who do
      not drink had lower odds for being a smoker compared to high risk drinkers and
      these odds decreased further during the observation period. CONCLUSION: The
      application of the VCM to the BRFS data in Italy has shown that this method can
      be useful in detecting which sub-populations require interventions. Although the
      results have shown a decrease in the odds of being a smoker for certain age
      groups and non-drinkers, other sub-populations have not decreased their odds and
      health inequalities remain. This observation indicates that efforts and
      interventions are still required to target these non-changing sub-populations in
      order to modify their smoking behaviour.

PMID- 25968887
TI  - KRAS Genomic Status Predicts the Sensitivity of Ovarian Cancer Cells to
      Decitabine.
AB  - Decitabine, a cancer therapeutic that inhibits DNA methylation, produces variable
      antitumor response rates in patients with solid tumors that might be leveraged
      clinically with identification of a predictive biomarker. In this study, we
      profiled the response of human ovarian, melanoma, and breast cancer cells treated
      with decitabine, finding that RAS/MEK/ERK pathway activation and DNMT1 expression
      correlated with cytotoxic activity. Further, we showed that KRAS genomic status
      predicted decitabine sensitivity in low-grade and high-grade serous ovarian
      cancer cells. Pretreatment with decitabine decreased the cytotoxic activity of
      MEK inhibitors in KRAS-mutant ovarian cancer cells, with reciprocal
      downregulation of DNMT1 and MEK/ERK phosphorylation. In parallel with these
      responses, decitabine also upregulated the proapoptotic BCL-2 family member
      BNIP3, which is known to be regulated by MEK and ERK, and heightened the activity
      of proapoptotic small-molecule navitoclax, a BCL-2 family inhibitor. In a
      xenograft model of KRAS-mutant ovarian cancer, combining decitabine and
      navitoclax heightened antitumor activity beyond administration of either compound
      alone. Our results define the RAS/MEK/DNMT1 pathway as a determinant of
      sensitivity to DNA methyltransferase inhibition, specifically implicating KRAS
      status as a biomarker of drug response in ovarian cancer.

PMID- 25968889
TI  - Relationships between vertebral fractures, sex hormones and vitamin D in Moroccan
      postmenopausal women: a cross sectional study.
AB  - BACKGROUND: Vertebral Fractures (VFs) are associated with bone loss that occurs
      before menopause but is accelerated at menopause as a result of sex hormone
      deficiency. To determine the association of sex hormones, bone remodeling markers
      and vitamin D levels with bone mineral density (BMD) and asymptomatic VFs
      prevalence using vertebral fracture assessment (VFA) in a cohort of Moroccan
      menopausal women. METHODS: This was a cross-sectional study conducted from
      October 2012 to April 2013 with menopausal women aged 50 years old and over. A
      total of 207 women who had no previous diagnosis of osteoporosis were enrolled in
      this cross-sectional study. Women were recruited prospectively from our
      laboratory department. VFA images and scans of the lumbar spine and proximal
      femur were obtained using a GE Healthcare Lunar Prodigy densitometer. VFs were
      defined using a combination of Genant semiquantitative approach and morphometry.
      Serum levels of estradiol, dehydroepiandrosterone sulfate, Sex hormone binding
      globulin, vitamin D, Osteocalcin, Crosslaps, intact parathormone were measured by
      Electrochemiluminescent immunoassay technique. RESULTS: Among the 207 women, 18.3
      % (n = 38) had densitometric osteoporosis. On VFA, VFs were detected in 134 (62.3
      %), including 96 (44.6 %) grade 1 and 38 (17.6 %) grade 2/3. There was no
      difference in the plasma levels of sex steroids, bone remodeling markers and
      vitamin D in the group of women with VFs (grade 1 and grade 2/3) and without VFs.
      The combination of variables that best predicted grade 2/3 VFs included the
      number of years since menopause and the lumbar spine T-score. CONCLUSION: These
      data confirm the importance of postmenopausal estrogen and SHBG concentrations in
      the bone loss and the pathogenesis of osteoporosis in elderly women, but not in
      the occurrence of the VFs.

PMID- 25968890
TI  - PerR controls oxidative stress defence and aerotolerance but not motility
      associated phenotypes of Campylobacter jejuni.
AB  - The foodborne bacterial pathogen Campylobacter jejuni is an obligate
      microaerophile that is exposed to atmospheric oxygen during transmission through
      the food chain. Survival under aerobic conditions requires the concerted control
      of oxidative stress systems, which in C. jejuni are intimately connected with
      iron metabolism via the PerR and Fur regulatory proteins. Here, we have
      characterized the roles of C. jejuni PerR in oxidative stress and motility
      phenotypes, and its regulon at the level of transcription, protein expression and
      promoter interactions. Insertional inactivation of perR in the C. jejuni
      reference strains NCTC 11168, 81-176 and 81116 did not result in any growth
      deficiencies, but strongly increased survival in atmospheric oxygen conditions,
      and allowed growth around filter discs infused with up to 30 % H2O2 (8.8 M).
      Expression of catalase, alkyl hydroperoxide reductase, thioredoxin reductase and
      the Rrc desulforubrerythrin was increased in the perR mutant, and this was
      mediated at the transcriptional level as shown by electrophoretic mobility shift
      assays of the katA, ahpC and trxB promoters using purified PerR. Differential RNA
      sequencing analysis of a fur perR mutant allowed the identification of eight
      previously unknown transcription start sites of genes controlled by Fur and/or
      PerR. Finally, inactivation of perR in C. jejuni did not result in reduced
      motility, and did not reduce killing of Galleria melonella wax moth larvae. In
      conclusion, PerR plays an important role in controlling oxidative stress
      resistance and aerobic survival of C. jejuni, but this role does not extend into
      control of motility and associated phenotypes.

PMID- 25968891
TI  - June 2015 update.

PMID- 25968892
TI  - What is so special about female sexual offenders? Introduction to the special
      issue on female sexual offenders.

PMID- 25968893
TI  - Pesticide levels and environmental risk in aquatic environments in China--A
      review.
AB  - China is one of the largest producers and consumers of pesticides in the world
      today. Along with the widespread use of pesticides and industrialization, there
      is a growing concern for water quality. The present review aims to provide an
      overview of studies on pesticides in aquatic environments in China. The levels in
      the water, sediment and biota were scored according to a detailed environmental
      classification system based on ecotoxicological effect, which is therefore a
      useful tool for assessing the risk these compounds pose to the aquatic ecosystem.
      Our review reveals that the most studied areas in China are the most populated
      and the most developed economically and that the most frequently studied
      pesticides are DDT and HCH. We show maps of where studies have been conducted and
      show the ecotoxicological risk the pesticides pose in each of the matrices. Our
      review pinpoints the need for biota samples to assess the risk. A large fraction
      of the results from the studies are given an environmental classification of
      "very bad" based on levels in biota. In general, the risk is higher for DDT than
      HCH. A few food web studies have also been conducted, and we encourage further
      study of this important information from this region. The review reveals that
      many of the most important agricultural provinces (e.g., Henan, Hubei and Hunan)
      with the largest pesticide use have been the subject of few studies on the
      environmental levels of pesticides. We consider this to be a major knowledge gap
      for understanding the status of pesticide contamination and related risk in
      China. Furthermore, there is also a lack of studies in remote Chinese
      environments, which is also an important knowledge gap. The compounds analyzed
      and reported in the studies represent a serious bias because a great deal of
      attention is given to DDT and HCH, whereas the organophosphate insecticides
      dominating current use are less frequently investigated. For the future, we point
      to the need for an organized monitoring plan designed according to the knowledge
      gaps in terms of geographical distribution, compounds included, and risks. 

PMID- 25968894
TI  - Does Coordinated, Multidisciplinary Treatment Limit Medical Disability and
      Attrition Related to Spine Conditions in the US Navy?
AB  - BACKGROUND: Musculoskeletal conditions account for the largest proportion of
      cases resulting in early separation from the US Navy. This study evaluates the
      impact of the Spine Team, a multidisciplinary care group that included
      physicians, physical therapists, and a clinical psychologist, for the treatment
      of active-duty service members with work-disabling, nonspecific low back pain at
      the Naval Medical Center, Portsmouth, VA, USA. We compared the impact of the
      introduction of the Spine Team in limiting disability and attrition from work
      disabling spine conditions with the experience of the Naval Medical Center, San
      Diego, CA, USA, where there is no comparable spine team. QUESTIONS/PURPOSES: Is a
      multidisciplinary spine team effective in limiting disability and attrition
      related to work-disabling spine conditions as compared with the current standard
      of care for US military active-duty service members? METHODS: This is a
      retrospective, pre-/post-study with a separate, concurrent control group using
      administratively collected data from two large military medical centers during
      the period 2007 to 2009. In this study, disability is expressed as the proportion
      of active-duty service members seeking treatment for a work-disabling spine
      condition that results in the assignment of a first-career limited-duty status.
      Attrition is expressed as the proportion of individuals assigned a first-career
      limited-duty status for a work-disabling spine condition who were referred to a
      Physical Evaluation Board. We analyzed 667 individuals assigned a first-career
      limited-duty for a work-disabling spine condition between 2007 and 2009 who
      received care at the Naval Medical Center Portsmouth or Naval Medical Center San
      Diego. RESULTS: Rates of first-career limited-duty assignments for spine
      conditions decreased from 2007 to 2009 at both sites, but limited-duty rates
      decreased to a greater extent at the intervention site (Naval Medical Center
      Portsmouth; from 8.5 per 100 spine cases in 2007 to 5.1 per 100 cases in 2009, p
      < 0.001) as compared with the control site (Naval Medical Center San Diego; 16.0
      per 100 spine cases in 2007 and 14.1 per 100 cases in 2009, p = 0.38) after the
      Spine Team was implemented in 2008. The risk of disability was lower at Naval
      Medical Center Portsmouth as compared with Naval Medical Center San Diego for
      each of the 3 years studied (in 2007, the relative risk was 0.53 [95% confidence
      limit {CL}, 0.42-0.68; p < 0.001]) indicating a protective effect of Naval
      Medical Center Portsmouth in limiting disability (in 2008, it was 0.58 [95% CL,
      0.45-0.73; p < 0.001] and in 2009 0.34 [95% CL, 0.27-0.47; p < 0.001]); the
      relative risk improved in 2009 after the introduction of the Spine Team at Naval
      Medical Center Portsmouth. There were no differences observed in rates of
      attrition from the period before the introduction of the Spine Team to after at
      Naval Medical Center Portsmouth, and no overall differences could be
      statistically detected between the two sites. CONCLUSIONS: This study provides
      suggestive evidence that a multi-disciplinary Spine Team may be effective in
      limiting disability. No conclusion can be drawn about the Spine Team's
      effectiveness in limiting attrition. Additional study is warranted to examine the
      effect of the timing of the introduction of multidisciplinary care for work
      disabling spine conditions. LEVEL OF EVIDENCE: Level III, therapeutic study.

PMID- 25968895
TI  - Tantalum Cones Provide Durable Mid-term Fixation in Revision TKA.
AB  - BACKGROUND: Multiple studies have reported favorable short-term outcomes using
      tantalum cones to reconstruct massive bone defects during revision TKA. However,
      longer-term followup is needed to determine the durability of these
      reconstructions. QUESTIONS/PURPOSES: We wished to determine the mid-term (1)
      reoperation rates for septic and aseptic causes, (2) radiologic findings of
      osseointegration, and (3) clinical outcomes based on the Knee Society score in
      patients who underwent revision knee arthroplasty with tantalum cones for severe
      bone loss. METHODS: We retrospectively evaluated records of 18 patients (18
      knees) who underwent revision knee arthroplasty with use of tantalum cones
      between 2005 and 2008; the primary indications for use of this approach were to
      reconstruct massive bone defects classified as Anderson Orthopaedic Research
      Institute Types 2B and 3. During this period, all defects of this type were
      treated with this approach and no cones were used for more-minor defects. A total
      of 26 cones (13 tibial and 13 femoral) were implanted. There were 12 female and
      six male patients with a mean age of 73 years (range, 55-84 years) at the time of
      revision. The indication for the revision included aseptic loosening (five
      patients) and second-stage reimplantation for deep infection (13 patients).
      Patients were followed for a mean of 6 years (range, 5-8 years). No patient was
      lost to followup. Clinical and radiographic outcomes were assessed with the Knee
      Society clinical rating system and radiographic evaluation system. RESULTS: There
      have been two reoperations for recurrent infection; at surgery, the two cones
      showed osseointegration. No evidence of loosening or migration of any implant was
      noted on the most recent radiographs. Knee Society knee scores improved from a
      mean of 31 points before surgery to 77 points at latest followup (p < 0.001), and
      function scores improved from a mean of 22 points to 65 points (p < 0.001).
      CONCLUSIONS: Tantalum cones for reconstruction of massive bone defects in
      revision knee arthroplasty provided secure fixation with excellent results at
      average followup of 6 years, although this series included relatively few
      patients. These devices are a viable option for surgeons to use in situations
      with severe bone loss. Further studies with longer followups are needed to
      confirm the durability of these reconstructions. LEVEL OF EVIDENCE: Level IV,
      therapeutic study.

PMID- 25968896
TI  - Periprosthetic femoral fracture fixation: a biomechanical comparison between
      proximal locking screws and cables.
AB  - BACKGROUND: The incidence of periprosthetic femoral fractures (PFF) around a
      stable stem is increasing. The aim of this biomechanical study was to examine how
      three different methods of fixation, for Vancouver type B1 PFF, alter the
      stiffness and strain of a construct under various configurations, in order to
      gain a better insight into the optimal fixation method. METHODS: Three different
      combinations of proximal screws and Dall-Miles cables were used: (A) proximal
      unicortical locking screws alone; (B) proximal cables and unicortical locking
      screws; (C) proximal cable alone, each in combination with distal bicortical
      locking screws, to fix a stainless steel locking compression plate to five
      synthetic femora with simulated Vancouver type B1 PFFs. In one synthetic femora,
      there was a 10-mm fracture gap, in order to simulate a comminuted injury. The
      other four femora had no fracture gap, to simulate a stable injury. An axial load
      was applied to the constructs at varying degrees of adduction, and the overall
      construct stiffness and surface strain were measured. RESULTS: With regards to
      stiffness, in both the gap and no gap models, method of fixation A was the
      stiffest form of fixation. The inclusion of the fracture gap reduced the
      stiffness of the construct quite considerably for all methods of fixation. The
      strain across both the femur and the plate was considerably less for method of
      fixation C, compared to A and B, at the locations considered in this study.
      CONCLUSION: This study highlights that the inclusion of cables appears to damage
      the screw fixations and does not aid in construct stability. Furthermore, the
      degree of fracture reduction affects the whole construct stability and the
      bending behaviour of the fixation.

PMID- 25968898
TI  - CBP-dependent Wnt/beta-catenin signaling is crucial in regulation of MDR1
      transcription.
AB  - Aberrant expression of the MDR1-encoded P-glycoprotein (P-gp) is often associated
      with clinical multi-drug resistance (MDR) leading to poor prognosis and failure
      of chemotherapy. However, the precise and cooperative molecular mechanism
      responsible for MDR1 transcription and expression in acquired MDR remains
      elusive. We, herein, demonstrate that Wnt/beta-catenin signal pathway is
      constitutively activated in Doxorubicin-induced MDR cancer cells, in which
      nuclear beta -catenin specifically interacts with the transcriptional coactivator
      CBP in a MEK(1/2)/ERK(1/2) signal-dependent manner. Specific knockdown of both
      beta-catenin and CBP by RNAi-mediated depletion abrogates MDR1 transcription and
      expression resulting in a complete reversal of P-gp-dependent efflux function and
      restoration of sensitivity to the Doxorubincin-induced cytotoxicity. Moreover,
      following pharmacological disruption of CBP and beta - catenin interaction
      through inhibition of the MEK(1/2)/ERK(1/2) signal by the specific inhibitor
      PD98059, MDR1 transcription and its encoded P-gp-dependent function are
      abolished. These findings conclude that the CBP/beta-catenin complex is a core
      component of the MDR1 transcriptional "enhancesome".

PMID- 25968897
TI  - Who let the dogs out?: detrimental role of Galectin-3 in hypoperfusion-induced
      retinal degeneration.
AB  - BACKGROUND: Retinal ischemia results in a progressive degeneration of neurons and
      a pathological activation of glial cells, resulting in vision loss. In the brain,
      progressive damage after ischemic insult has been correlated to neuroinflammatory
      processes involving microglia. Galectin-3 has been shown to mediate microglial
      responses to ischemic injury in the brain. Therefore, we wanted to explore the
      contribution of Galectin-3 (Gal-3) to hypoperfusion-induced retinal degeneration
      in mice. METHODS: Gal-3 knockout (Gal-3 KO) and wildtype (WT) C57BL/6 mice were
      subjected to chronic cerebral hypoperfusion by bilateral narrowing of the common
      carotid arteries using metal coils resulting in a 30% reduction of blood flow.
      Sham operated mice served as controls. After 17 weeks, the mice were sacrificed
      and the eyes were analyzed for retinal architecture, neuronal cell survival, and
      glial reactivity using morphological staining and immunohistochemistry. RESULTS:
      Hypoperfusion caused a strong increase in Gal-3 expression and microglial
      activation in WT mice, coupled with severe degenerative damage to all retinal
      neuronal subtypes, remodeling of the retinal lamination and Muller cell gliosis.
      In contrast, hypoperfused Gal-3 KO mice displayed a retained laminar
      architecture, a significant preservation of photoreceptors and ganglion cell
      neurons, and an attenuation of microglial and Muller cell activation. CONCLUSION:
      Moderate cerebral blood flow reduction in the mouse results in severe retinal
      degenerative damage. In mice lacking Gal-3 expression, pathological changes are
      significantly attenuated. Gal-3 is thereby a potential target for treatment and
      prevention of hypoperfusion-induced retinal degeneration and a strong candidate
      for further research as a factor behind retinal degenerative disease.

PMID- 25968899
TI  - Bone Metastasis: Molecular Mechanisms Implicated in Tumour Cell Dormancy in
      Breast and Prostate Cancer.
AB  - Metastasis to the bone is most frequently observed in advanced cases of breast
      and prostate cancer. The latent development of overt metastatic lesions is
      associated with debilitating skeletal morbidity and eventual patient mortality.
      Secondary tumours in bone are derived from disseminated tumour cells (DTCs) that
      enter into a state of cellular dormancy. The dormant state confers resistance to
      conventional chemotherapeutic agents and prevents elimination of DTCs from the
      bone using current drug therapies. Expansion of our presently limited
      understanding of the molecular mechanisms underpinning disseminated breast and
      prostate tumour cell dormancy is critical to the future development of novel drug
      therapies aimed at the removal of DTCs, and thereby, the prevention of bone
      metastasis. This review provides an overview of the main putative molecular
      mechanisms underlying cellular dormancy in breast and prostate cancer bone
      metastasis reported from multiple experimental in vitro and in vivo models. 

PMID- 25968900
TI  - 11-Phenylundeca-5Z,9Z-dienoic Acid: Stereoselective Synthesis and Dual
      Topoisomerase I/IIalpha Inhibition.
AB  - (5Z,9Z)-11-Phenylundeca-5,9-dienoic acid was stereoselectively synthesized, based
      on original cross-cyclomagnesiation of 2-(hepta-5,6-dien-1-yloxy)tetrahydro-2H
      pyran and buta-2,3-dien-1-ylbenzene with EtMgBr in the presence of the Cp2TiCl2
      catalyst giving 2,5-dialkylydenemagnesacyclopentane in 86% yield. The acid
      hydrolysis of the product and Jones oxidation of the resulting 2-{[(5Z,9Z)-11
      phenylundeca-5,9-dien-1-yl]oxy}tetrahydro-2N-pyran afforded (5Z,9Z)-11
      phenylundeca-5,9-dienoic acid in an overall yield of 75%. A high inhibitory
      activity of the synthesized acid with respect to human topoisomerase I (hTop1)
      and II (hTop2alpha) was detected. Resorting to the data of molecular docking, a
      mechanism of inhibition was proposed. 

PMID- 25968901
TI  - Hyperuricaemia is associated with renal damage independently of hypertension and
      intrarenal renin-angiotensin system activation, as well as their circadian
      rhythms.
AB  - AIM: Both hyperuricaemia and activation of the intrarenal renin-angiotensin
      system (RAS) play an important role in the development of hypertension and renal
      damage. However, it has not been clear whether hyperuricaemia is associated with
      renal damage due to hypertension or intrarenal RAS activation, as well as their
      circadian rhythms. METHODS: We recruited 43 chronic kidney disease (CKD) patients
      who did not receive RAS blockers and antihyperuricaemic drugs, and investigated
      the relationship among serum uric acid (sUA) levels, the circadian rhythm of
      urinary angiotensinogen (U-AGT) excretion levels, and the levels of albuminuria
      (U-ACR) and proteinuria (U-P/Cr). RESULTS: sUA levels were significantly
      associated with estimated glomerular filtration rate (eGFR) (P = 0.002), systolic
      blood pressure (SBP) (daytime, P = 0.031), and U-ACR (daytime, P = 0.006 and
      nighttime, P = 0.008) and U-P/Cr (daytime, P = 0.017 and nighttime, P = 0.013).
      However, there were no significant differences between sUA levels and SBP in
      nighttime and U-AGT excretion levels in both time periods. Multiple regression
      analyses for sUA levels were performed using age, sex, eGFR and each parameter
      (SBP, U-AGT/Cr, U-ACR or U-P/Cr). sUA levels were not associated with SBP or U
      AGT/Cr in both time periods. sUA levels tended to correlate with U-P/Cr levels in
      nighttime, and were significantly associated with U-P/Cr in daytime (P = 0.026)
      and U-ACR in daytime (P = 0.017) and nighttime (P = 0.046). Moreover, no
      significant differences were found between sUA levels and night-to-day ratios of
      some parameters. CONCLUSION: These data suggest that hyperuricaemia is associated
      with renal damage, independently of hypertension and intrarenal RAS activation,
      as well as their circadian rhythms.

PMID- 25968902
TI  - The prognostic significance of HOTAIR for predicting clinical outcome in patients
      with digestive system tumors.
AB  - PURPOSE: Although some studies have assessed the prognostic value of HOTAIR in
      patients with digestive system tumors, the relationship between the HOTAIR and
      outcome of digestive system tumors remains unknown. METHODS: The PubMed was
      searched to identify the eligible studies. Here, we performed a meta-analysis
      with 11 studies, including a total of 903 cases. Pooled hazard ratios (HRs) and
      95 % confidence interval (CI) of HOTAIR for cancer survival were calculated.
      RESULTS: We found that the pooled HR elevated HOTAIR expression in tumor tissues
      was 2.36 (95 % CI 1.88-2.97) compared with patients with low HOTAIR expression.
      Moreover, subgroup analysis revealed that HOTAIR overexpression was also markedly
      associated with short survival for esophageal squamous cell carcinoma (HR 2.19,
      95 % CI 1.62-2.94) and gastric cancer (HR 1.66, 95 % CI 1.02-2.68). In addition,
      up-regulated HOTAIR was significantly related to survival of digestive system
      cancer among the studies with more follow-up time (follow time >= 5 years) (HR
      2.51, 95 % CI 1.99-3.17). When stratified by HR resource and number of patients,
      the result indicated consistent results with the overall analysis. Subgroup
      analysis on ethnicities did not change the prognostic influence of elevated
      HOTAIR expression. Additionally, we conducted an independent validation cohort
      including 71 gastric cancer cases, in which patients with up-regulated HOTAIR
      expression had an unfavorable outcome with HR of 2.10 (95 % CI 1.10-4.03).
      CONCLUSION: The results suggest that aberrant HOTAIR expression may serve as a
      candidate positive marker to predict the prognosis of patients with carcinoma of
      digestive system.

PMID- 25968903
TI  - Changing incidence of myeloproliferative neoplasms: trends and subgroup risk
      profiles in the USA, 1973-2011.
AB  - PURPOSE: Recent diagnostic and cancer reporting changes influencing
      myeloproliferative neoplasms (MPNs) encourage the assessment of trends and
      examination of the recently identified MPN subtypes: polycythemia vera (PV),
      essential thrombocythemia (ET), and primary myelofibrosis (PMF), across the age
      continuum by race and ethnicity. METHODS: Surveillance, Epidemiology, and End
      Results data provided MPN incidence data since 1973 and MPN subtype data since
      2001. Joinpoint regression estimated annual percent changes. Poisson regression
      estimated risk ratios. RESULTS: The 2005 JAK2 V617F discovery and the 2008 WHO
      diagnostic guideline for the JAK2 V617F mutation coincide with a 31 % increase in
      ET and a 21 % decrease in PV incidence rates. We found that younger women had a
      13-33 % higher ET risk and that women under the age of 34 had a 58 % higher PMF
      risk, relative to men. Blacks, aged 35-49 with a higher ET risk, also had a 69 %
      higher PMF risk relative to whites. CONCLUSION: Demographic characteristic of ET
      and PMF patients may be useful for improving risk prediction and informing
      clinical screening and treatment strategies. Changing guidelines, new
      discoveries, and in-depth analysis of a large population-based study have
      implications for accurately identifying incident cases of MPNs, MPN subgroups,
      and health resource planning.

PMID- 25968904
TI  - The non-muscle-myosin-II heavy chain Myh9 mediates colitis-induced epithelium
      injury by restricting Lgr5+ stem cells.
AB  - Lgr5+ stem cells are crucial to gut epithelium homeostasis, and therapies
      targeting these cells hold promise for treatment of gastrointestinal diseases.
      Here we report that the non-muscle-myosin-II (NMII) heavy chain Myh9 accumulates
      at epithelial injury sites in mice distal colon treated with dextran sulphate
      sodium (DSS). Gut-epithelium-specific Myh9 monoallelic deletion alleviates DSS
      induced colonic crypt damage and acute colitis. Consistently, the NMII inhibitor
      blebbistatin can improve the survival of Lgr5+ stem cells and the growth of Lgr5
      organoids. Mechanistically, inhibition of NMII by blebbistatin or Myh9
      monoallelic deletion activates Akt through Rac1 and PAK1, which is essential for
      the survival and pluripotency of Lgr5+ cells. These results establish a critical
      role of the Myh9-Rac1-PAK1-Akt pathway in the maintenance of Lgr5+ stem cells. As
      blebbistatin can mitigate DSS-induced colitis and preserve Lgr5+ colonic stem
      cells in vivo, our findings provide a potential therapeutic intervention of
      gastrointestinal epithelium injury and degenerative diseases. 

PMID- 25968906
TI  - [Experiencing dementia: evaluation of Into D'mentia].
AB  - BACKGROUND: Most persons with dementia in the Netherlands live at home, where
      they are cared for by informal carers such as family members or friends, who
      offer this care unpaid. Their care-task poses a high burden on these informal
      carers, increasing the risk of health problems and social isolation. Many
      informal carers indicate they want more information on the behaviour of those
      they care for. AIM: To develop and evaluate Into D'mentia, a simulation set in a
      living kitchen in which visitors experience a day in the life of someone with
      dementia. During this 'day', modern techniques such as sensors and projections,
      simulate the limitations of having dementia. This intervention is evaluated on
      usefulness and user friendliness, and on its effect on empathy, attitudes towards
      dementia, coping, carer burden, person-centered care capabilities and care
      satisfaction. RESEARCH: Nine informal carers and 23 care professionals took part
      in the research into the Into D'mentia simulation. Before and after their visit,
      they filled in several questionnaires, with, among others, their opinion on the
      usefulness and user friendliness of this experience. RESULTS: Participants found
      Into D'mentia a highly useful and user friendly development. They indicated that
      the simulation offered good insight in the life of someone with dementia, and
      that they could offer better care thanks to this experience. Participants also
      indicated that they often thought back on their experiences in the simulation, in
      order to better understand the behaviour of people with dementia. CONCLUSION:
      Into D'mentia offers a unique, accessible way to experience the limitations
      dementia has on daily life. Users indicate that it is a useful and user friendly
      innovation. Into D'mentia appears to be a suitable method to support informal and
      professional caregivers.

PMID- 25968905
TI  - Changes in autumn senescence in northern hemisphere deciduous trees: a meta
      analysis of autumn phenology studies.
AB  - BACKGROUND AND AIMS: Many individual studies have shown that the timing of leaf
      senescence in boreal and temperate deciduous forests in the northern hemisphere
      is influenced by rising temperatures, but there is limited consensus on the
      magnitude, direction and spatial extent of this relationship. METHODS: A meta
      analysis was conducted of published studies from the peer-reviewed literature
      that reported autumn senescence dates for deciduous trees in the northern
      hemisphere, encompassing 64 publications with observations ranging from 1931 to
      2010. KEY RESULTS: Among the meteorological measurements examined, October
      temperatures were the strongest predictors of date of senescence, followed by
      cooling degree-days, latitude, photoperiod and, lastly, total monthly
      precipitation, although the strength of the relationships differed between high-
      and low-latitude sites. Autumn leaf senescence has been significantly more
      delayed at low (25 degrees  to 49 degrees N) than high (50 degrees  to 70 degrees
      N) latitudes across the northern hemisphere, with senescence across high-latitude
      sites more sensitive to the effects of photoperiod and low-latitude sites more
      sensitive to the effects of temperature. Delays in leaf senescence over time were
      stronger in North America compared with Europe and Asia. CONCLUSIONS: The results
      indicate that leaf senescence has been delayed over time and in response to
      temperature, although low-latitude sites show significantly stronger delays in
      senescence over time than high-latitude sites. While temperature alone may be a
      reasonable predictor of the date of leaf senescence when examining a broad suite
      of sites, it is important to consider that temperature-induced changes in
      senescence at high-latitude sites are likely to be constrained by the influence
      of photoperiod. Ecosystem-level differences in the mechanisms that control the
      timing of leaf senescence may affect both plant community interactions and
      ecosystem carbon storage as global temperatures increase over the next century.

PMID- 25968907
TI  - [Intramural nursing home care for patients with psychiatric-somatic
      multimorbidity: specialty care of patients slip through the safety net? ].

PMID- 25968908
TI  - A Qualitative Study of Older Adults and Staff at an Adult Day Center in a
      Cambodian Community in the United States.
AB  - PURPOSE: Adult day care programs in the United States are seeing an increase in
      culturally diverse patients. The purpose of this study was to better understand
      the subjective experiences of staff and Cambodian refugees attending an adult day
      center in the United States that provides services focused on the cultural needs
      of the older adults, such as Cambodian food, activities, and Cambodian staff.
      DESIGN: This is a qualitative study using grounded theory to analyze 10
      individual interviews from staff members and 80 individual interviews from
      participants who attend an adult day care program for Cambodians in a city in the
      northeast United States. FINDINGS: Three primary themes emerged: The participants
      felt respected, there was a generational tension between the young staff and the
      participants, and the center acted as a cultural liaison between the medical
      providers and the participants.

PMID- 25968909
TI  - Achieving the Optimal Peri-implant Soft Tissue Profile by the Selective Pressure
      Method via Provisional Restorations in the Esthetic Zone.
AB  - For the successful single-tooth implant therapy in the esthetics zone, achieving
      an ideal peri-implant soft tissue profile is paramount. It can achieve by the
      manipulation of the provisional restorations. This clinical report demonstrate
      the selective pressure method and concave transmucosal profile of the provisional
      restorations to achieve the ideal and stable gingival profile in esthetic single
      tooth implant restorations. CLINICAL SIGNIFICANCE: The selective pressure method
      and the concave transmucosal profile in implant provisional restorations
      facilitate stable and harmonized peri-implant gingival tissue in the esthetic
      zone.

PMID- 25968910
TI  - Impaired discrimination learning in interneuronal NMDAR-GluN2B mutant mice.
AB  - Previous studies have established a role for N-methyl-D-aspartate receptor
      (NMDAR) containing the GluN2B subunit in efficient learning behavior on a variety
      of tasks. Recent findings have suggested that NMDAR on GABAergic interneurons may
      underlie the modulation of striatal function necessary to balance efficient
      action with cortical excitatory input. Here we investigated how loss of GluN2B
      containing NMDAR on GABAergic interneurons altered corticostriatal-mediated
      associative learning. Mutant mice (floxed-GluN2B*Ppp1r2-Cre) were generated to
      produce loss of GluN2B on forebrain interneurons and phenotyped on a touchscreen
      based pairwise visual learning paradigm. We found that the mutants showed normal
      performance during Pavlovian and instrumental pretraining, but were significantly
      impaired on a discrimination learning task. Detailed analysis of the
      microstructure of discrimination performance revealed reduced win->stay behavior
      in the mutants. These results further support the role of NMDAR, and GluN2B in
      particular, on modulation of striatal function necessary for efficient choice
      behavior and suggest that NMDAR on interneurons may play a critical role in
      associative learning.

PMID- 25968911
TI  - Loss of S-100-positive Schwann cells is a feature of JAK2 V617F-positive
      myeloproliferative neoplasm.

PMID- 25968912
TI  - Severe sustained hypoplastic bone marrow after immunosuppressive therapy in
      malignant lymphoma cases with anti-centromere protein-B antibody.

PMID- 25968914
TI  - Quercetin regulates beta-catenin signaling and reduces the migration of triple
      negative breast cancer.
AB  - Triple negative breast cancer (TNBC) is characterized by a lack in estrogen,
      progesterone, and epidermal growth factor 2 receptors. TNBC exhibits most of the
      characteristics of basal-like and claudin-low breast cancer subtypes. The main
      contributor in the mortality of TNBC is due to the higher invasive and migratory
      ability of these tumor cells. Some plant flavonoids inhibit the epithelial
      mesenchymal transition (EMT) of tumor cells and suppress cancer metastasis. In
      this study, we aimed to determine whether the flavonoid quercetin is effective in
      modulating the molecular signaling associated with EMT in TNBC. Our data
      indicated that quercetin can induce the expression of E-cadherin and also
      downregulate vimentin levels in TNBC. The ability of quercetin to modulate these
      EMT markers resulted in a mesenchymal-to-epithelial transition (MET). Quercetin
      induced MET was linked with the alteration of nuclear localization of beta
      catenin and modulation of beta-catenin target genes such as cyclin D1 and c-Myc.
      Furthermore, we observed that quercetin induced the anti-tumor activity of
      doxorubicin by inhibiting the migratory ability of TNBC cells. These results
      suggested that quercetin may inhibit TNBC metastasis and also improve the
      therapeutic efficacy of existing chemotherapeutic drugs.

PMID- 25968915
TI  - Electrocardiographic parameters predict super-response in cardiac
      resynchronization therapy.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) is an established treatment
      for heart failure patients. However, determinants of response to CRT remain
      elusive. The aim of the study was to assess the value of ECG parameters to
      predict super-response in CRT patients. METHODS: A 12-lead surface ECG was
      recorded at baseline and immediately after CRT-device implantation. Baseline ECG
      parameters (QRS duration, bundle branch morphology, axis, PR interval, QTc,
      intrinsicoid deflection) and post-implant paced QRS duration were analyzed;
      relative change in QRS duration was calculated. Decrease of left ventricular end
      systolic volume >=30% after 12 months was classified as super-response. RESULTS:
      In group of 101 patients, 32 (31.7%) were super-responders. There were no
      significant differences in baseline ECG parameters between super-responders and
      other patients. Post-implant QRS duration was shorter in super-responders (148 +/
      22 ms vs. 162 +/- 28 ms; P=0.010). Only in super-responders was significant QRS
      reduction observed after implantation. Relative QRS shortening was higher in
      super-responders (12.1% (6.8 to 22.2) vs. 1.7% (-11.9 to 11.8); P=0.005). In a
      multivariable analysis post-implant QRS duration and relative QRS shortening
      remained independent predictor of super-response. CONCLUSION: Absolute post
      implant QRS duration and relative QRS shortening are the only ECG parameters
      associated with super-response in CRT. Further prospective studies on larger
      population are warranted to determine our findings.

PMID- 25968913
TI  - The mechanotransduction machinery at work at adherens junctions.
AB  - The shaping of a multicellular body, and the maintenance and repair of adult
      tissues require fine-tuning of cell adhesion responses and the transmission of
      mechanical load between the cell, its neighbors and the underlying extracellular
      matrix. A growing field of research is focused on how single cells sense
      mechanical properties of their micro-environment (extracellular matrix, other
      cells), and on how mechanotransduction pathways affect cell shape, migration,
      survival as well as differentiation. Within multicellular assemblies, the
      mechanical load imposed by the physical properties of the environment is
      transmitted to neighboring cells. Force imbalance at cell-cell contacts induces
      essential morphogenetic processes such as cell-cell junction remodeling, cell
      polarization and migration, cell extrusion and cell intercalation. However, how
      cells respond and adapt to the mechanical properties of neighboring cells,
      transmit forces, and transform mechanical signals into chemical signals remain
      open questions. A defining feature of compact tissues is adhesion between cells
      at the specialized adherens junction (AJ) involving the cadherin super-family of
      Ca(2+)-dependent cell-cell adhesion proteins (e.g., E-cadherin in epithelia).
      Cadherins bind to the cytoplasmic protein beta-catenin, which in turn binds to
      the filamentous (F)-actin binding adaptor protein alpha-catenin, which can also
      recruit vinculin, making the mechanical connection between cell-cell adhesion
      proteins and the contractile actomyosin cytoskeleton. The cadherin-catenin
      adhesion complex is a key component of the AJ, and contributes to cell assembly
      stability and dynamic cell movements. It has also emerged as the main route of
      propagation of forces within epithelial and non-epithelial tissues. Here, we
      discuss recent molecular studies that point toward force-dependent conformational
      changes in alpha-catenin that regulate protein interactions in the cadherin
      catenin adhesion complex, and show that alpha-catenin is the core mechanosensor
      that allows cells to locally sense, transduce and adapt to environmental
      mechanical constrains. 

PMID- 25968916
TI  - Single-lead portable ECG devices: Perceptions and clinical accuracy compared to
      conventional cardiac monitoring.
AB  - INTRODUCTION: Portable ECG devices are widely available yet there are limited
      data on their accuracy, physician and patient perceptions, and ease of use. The
      purpose of this study was to evaluate the accuracy of 4 single-lead portable ECG
      devices compared to a conventional 3-lead hospital cardiac monitor and to assess
      physician and patient perceptions of portable ECG devices. METHODS: Twenty
      consecutive hospitalized patients were provided 4 portable ECG devices for 30
      second cardiac rhythm recording. ECG rhythm strips from the portable ECG devices
      were interpreted by a group of 5 physician reviewers. The reviewers then compared
      the portable ECG device rhythm strips to simultaneously recorded hospital cardiac
      monitor rhythm strips to determine physician preference. A cardiac
      electrophysiologist interpreted ECG rhythm strips from the hospital cardiac
      monitor as the "gold standard." Rhythm interpretations of the portable ECG
      devices and the hospital cardiac monitor were analyzed to evaluate clinical
      accuracy. Patient perceptions were evaluated by a 20-item questionnaire. RESULTS:
      There was less than 50% concordance of portable ECG device rhythm strips with the
      hospital cardiac monitor (when uninterpretable rhythm strips were included).
      Physicians usually preferred interpreting ECGs from hospital cardiac monitors
      compared to portable ECG devices. Manufacturer instructions were insufficient to
      allow patients to operate portable ECG devices in a limited time. Most patients
      felt comfortable using a portable ECG device if prescribed by a physician.
      CONCLUSION: Portable ECG devices may be a reasonable option for long-term rhythm
      surveillance in select patients. Widespread use of these devices cannot be
      endorsed unless improvements in their accuracy are properly addressed.

PMID- 25968917
TI  - Primary Central Nervous System Posttransplant Lymphoproliferative Disease in a
      Bilateral Transfemoral Lower Extremity Transplantation Recipient.
AB  - Posttransplant lymphoproliferative disorder (PTLD) is a heterogeneous group of
      clinical and pathological entities characterized by malignant lymphoid cell
      proliferation occurring after solid organ transplantation, with frequent
      extranodal involvement. Central nervous system (CNS) involvement occurs in 7-15%
      of the cases and it is a significant negative prognostic factor. A case of
      primary CNS (PCNS) PTLD in the first bilateral lower limb transplant recipient is
      presented. 

PMID- 25968918
TI  - Lymphoproliferative Disorders in Patients with Chronic Myeloid Leukemia: A Single
      Center Case Series.
AB  - Lymphoproliferative disorders presenting simultaneously with or subsequent to the
      occurrence of chronic myeloid leukemia (CML) have rarely been reported. Herein,
      we report 8 cases of a variety of lymphoproliferative conditions associated with
      CML at different times during the course of the disease. All 8 patients were
      treated with tyrosine kinase inhibitors at some point during the course of their
      illness. The literature regarding the uncommon association of these apparently
      unrelated disorders is reviewed as well as the possible underlying mechanisms
      that could be associated with this phenomenon. 

PMID- 25968919
TI  - From coffee rings to coffee eyes.
AB  - We discuss how the stain left after evaporation of a suspension evolves with
      heating of the glass or plastic on which the liquid has been deposited. Upon
      increasing the substrate temperature, it is found that the stain gradually
      changes from the usually observed ring to an "eye" shape, that is, a combination
      of the thick central stain and the thin outer ring. Both the size and the
      relative volume of the central stain increase with the substrate temperature. The
      main mechanism for this phenomenon is proposed to be an enhanced Marangoni
      recirculation flow on hot substrates. These findings can be exploited to
      continuously tune the morphology of coffee stains, with potential applications in
      self-assembly and ink-jet printing. 

PMID- 25968921
TI  - Involvement of CYP 3A5 In the Interaction Between Tacrolimus and Nicardipine: A
      Case Report.
AB  - Tacrolimus is a calcineurin inhibitor primarily metabolized by CYP3A4 and
      secondarily by CYP3A5. Several drugs can modify tacrolimus blood levels as
      calcium channel blockers (CCBs). Interaction with nicardipine was reported in
      some cases. A man with a history of malignant arterial hypertension treated with
      nicardipine, underwent kidney transplantation. After transplantation, he was
      treated with tacrolimus, mycophenolate mofetil and corticoids. Therapeutic drug
      monitoring of tacrolimus was done regularly showing a mean trough concentration
      (C0) of 24.39 ng/mL with some concentrations reaching 52 ng/mL. After changing
      nicardipine by prazosine, the first tacrolimus C0 after stopping nicardipine was
      3.2 ng/mL. Increase of tacrolimus trough concentrations is due to the inhibition
      of CYP3A4. Very high levels of tacrolimus suggest the non expression of CYP3A5.
      Thus, because of the possible lack of the secondary pathway, therapeutic drug
      monitoring of tacrolimus is highly recommended at the introduction of CCBs and
      also at its stopping. 

PMID- 25968922
TI  - Ultrafast vibrational and structural dynamics of dimeric cyclopentadienyliron
      dicarbonyl examined by infrared spectroscopy.
AB  - In this work, we carry out steady-state, femtosecond pump-probe and two
      dimensional (2D) infrared spectroscopic studies on dimeric pi
      cyclopentadienyliron dicarbonyl [CpFe(CO)2]2 in the C=O stretching vibration
      frequency region in CCl4 and CH2Cl2. The cis and trans isomers, in terms of the
      position of two terminal C=O groups, are found to coexist in the two solvents. A
      weak asymmetric stretching peak of the cis-isomer is revealed under that of the
      IR-active trans-isomer by analyzing the 2D infrared cross peak, which is
      supported by ab initio computations. Furthermore, vibrational population
      relaxation is found to be both solute and solvent dependent (ranging from 21 ps
      to 32 ps)--the fastest dynamics is found for the trans-isomer in the polar
      solvent environment, which is believed to be associated with the availability and
      the number of efficient energy accepting channels for solvent molecules. The
      spectral diffusion dynamics of the C=O stretching vibrations, occurring on an
      even faster time scale (1 ps to 3 ps), mainly exhibits solvent dependence--faster
      dynamics is found in the polar solvent, involving weak and rapidly fluctuating
      hydrogen bonding interactions between CH2 groups of the solvent and the terminal
      carbonyls of solutes.

PMID- 25968920
TI  - Hhex is Required at Multiple Stages of Adult Hematopoietic Stem and Progenitor
      Cell Differentiation.
AB  - Hhex encodes a homeodomain transcription factor that is widely expressed in
      hematopoietic stem and progenitor cell populations. Its enforced expression
      induces T-cell leukemia and we have implicated it as an important oncogene in
      early T-cell precursor leukemias where it is immediately downstream of an LMO2
      associated protein complex. Conventional Hhex knockouts cause embryonic lethality
      precluding analysis of adult hematopoiesis. Thus, we induced highly efficient
      conditional knockout (cKO) using vav-Cre transgenic mice. Hhex cKO mice were
      viable and born at normal litter sizes. At steady state, we observed a defect in
      B-cell development that we localized to the earliest B-cell precursor, the pro-B
      cell stage. Most remarkably, bone marrow transplantation using Hhex cKO donor
      cells revealed a more profound defect in all hematopoietic lineages. In contrast,
      sublethal irradiation resulted in normal myeloid cell repopulation of the bone
      marrow but markedly impaired repopulation of T- and B-cell compartments. We noted
      that Hhex cKO stem and progenitor cell populations were skewed in their
      distribution and showed enhanced proliferation compared to WT cells. Our results
      implicate Hhex in the maintenance of LT-HSCs and in lineage allocation from
      multipotent progenitors especially in stress hematopoiesis.

PMID- 25968923
TI  - A 3D machine vision method for non-invasive assessment of respiratory function.
AB  - BACKGROUND: Respiratory function testing is important for detecting and
      monitoring illness, however, it is difficult for some patients, such as the young
      and severely ill, to perform conventional tests that require cooperation and/or
      patient contact. METHOD: A new method was developed for non-contact breathing
      measurement, employing photometric stereo to capture the surface topography of
      the torso of an unconstrained subject. The surface is integrated to calculate
      time-dependent volume changes during respiration. RESULTS: The method provides a
      useful means of continuously measuring volume changes during respiration with
      high spatial and temporal resolution. The system was tested by comparison with
      pneumotachometry equipment and a clear periodic signal, of a frequency
      corresponding to the reference data, was observed. CONCLUSION: The approach is
      unique in performing breathing monitoring (with potential diagnostic capability)
      for unconstrained patients in virtually any lighting conditions (including
      darkness during sleep) and in a non-contact, unobtrusive (i.e. using
      imperceptible light) fashion. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 25968924
TI  - Interprofessional communication training: benefits to practicing pharmacists.
AB  - BACKGROUND: Interprofessional communication skills are important for pharmacists
      to build collaborative relationships with other health professionals, integrate
      into healthcare teams, maximise their effectiveness in patient care in addressing
      complex care needs and meet the demands of health care reforms. OBJECTIVE: This
      qualitative study explores clinical pharmacists' experiences and reflections
      after completing a learning and practice module which introduced them to a
      framework for successful interprofessional communication. SETTING: The
      postgraduate clinical pharmacy program at The University of Queensland and the
      clinical pharmacy practice environments of forty-eight hospital and seven
      community based pharmacists. METHOD: A learning and practice module outlining a
      framework for successful interprofessional communication was designed and
      integrated into a postgraduate clinical pharmacy program. Enrolled pharmacists
      applied newly learnt communication skills in pro-actively initiated, clinical
      discussions with a health professional in their practice environment. They
      provided written reflections on their experiences which were analysed using
      thematic analysis. MAIN OUTCOME: Pharmacists' perceptions of the impact of
      applying the communication framework during their interaction with a health
      professional in their practice setting. RESULTS: Themes which emerged from
      reflections described pharmacists' confidence and capabilities to successfully
      conduct a clinical discussion with a health professional after initial
      apprehension and nervousness about the scheduled interaction. The application of
      the communication framework enhanced their perception of their professional
      identity, credibility and ability to build a collaborative working relationship
      with other health professionals. CONCLUSIONS: Pharmacists perceived that a
      learning and practice module for successful interprofessional practice integrated
      into a postgraduate clinical pharmacy program enhanced their interprofessional
      communication skills. The development of pro-active, interprofessional
      communication skills has the potential to increase interprofessional
      collaboration and pharmacists' personal role satisfaction. Pharmacists also
      observed it added value to their professional contribution in health care teams
      when addressing the demands of increasingly complex health care needs and
      reforms.

PMID- 25968925
TI  - Hyperacute stabilization (<12 hours) for polytrauma patients with unstable spinal
      fractures.
AB  - BACKGROUND: The objective of this study is to validate the safety of hyperacute
      stabilization. METHODS: Patient demographics, American Spinal Injury Association
      (ASIA) grade on initial evaluation and serial follow up grades, hospital length
      of stay, Intensive Care Unit length of stay, intraoperative blood loss,
      postoperative length of stay, comorbidities, Injury Severity Score and
      complications of recumbency were recorded. RESULTS: Corroborating previous
      studies, our study shows polytrauma patients undergoing a hyperacute
      stabilization of a spinal fracture displayed a trend towards better neurological
      outcome and decreased hospital stays while having a similar complication rate to
      those operated on in a delayed fashion. CONCLUSIONS: Hyperacute stabilization can
      be associated with improved ASIA grades even in complete injuries.

PMID- 25968926
TI  - Surgical treatment of cavernoma-related epilepsy.
AB  - Cerebral cavernous malformations (CCMs) are frequently associated with a seizure
      disorder, and the risk of developing drug-resistant epilepsy (DRE) is
      substantial, especially for temporal lobe lesions. This article includes a review
      of the literature on the surgical treatment of epilepsy associated to CCMs in the
      magnetic resonance imaging (MRI) era, as well as an analysis of the Authors'
      experience in this field. It is concluded that microsurgery is a valuable
      treatment option, which may provide excellent results on seizures, with 76% of
      patients on average being seizure-free after surgery. Nevertheless, the optimal
      surgical strategy to achieve seizure control has not been clearly identified, and
      several attitudes have been reported in the literature. The choice of
      lesionectomy, associated or not to removal of surrounding hemosiderin, versus
      resections extended to epileptogenic cortex depends on the accurate scrutiny of
      several factors, which should be investigated through an adequate epileptological
      presurgical workup. This should include an epilepsy-oriented brain MRI study,
      integrated by an appropriate neurophysiological and clinical assessment, and if
      needed by other functional evaluations. Besides representing the optimal option
      in CCM-related DRE cases, microsurgery should be considered also at seizure
      presentation or in cases with recent-onset sporadic seizures, to protect the
      patient from both the possible development of drug resistance and the risk of
      haemorrhage. 

PMID- 25968927
TI  - Radiosurgery for cerebral cavernomas.
AB  - The role of stereotactic radiosurgery (SRS) in the management of cerebral
      cavernomas (CCMs) remains controversial. However, during the last decade the
      increasing knowledge on natural history and numerous publications from SRS
      centers using modern treatment protocols has been changing the initial resistance
      of the neurosurgical community. Unfortunately, the quality of publications on CCM
      SRS remains heterogeneous. Controversies arise from the lack of control groups,
      the different definition of hemorrhage, heterogeneous patient populations, and
      poor definition of treatment protocols. The key for proper interpretation of
      results is the understanding of the natural history of CCMs, which is varied both
      according to anatomical location and the presence or absence of previous
      hemorrhage. Hemispheric lesions appear to be more benign with lower annual bleed
      rate and risk of persisting disability, whereas those found in the thalamus,
      basal ganglia and brainstem typically have higher rebleed risk resulting in
      higher cumulative morbidity following subsequent hemorrhages. However, we are
      still unable at presentation to predict the future behavior of an individual
      lesion. In the present paper we critically review and analyze the modern SRS
      literature on CCMs. The expanding number of available data with current treatment
      protocols strongly supports the initial intuition that SRS is an effective
      treatment alternative for deep-seated CCMs with multiple hemorrhages reducing
      pretreatment annual rebleed rates from 32% pre-treatment to 1.5% within 2 years
      after treatment (N.=197). Moreover, it appears to stabilize lesions with no more
      than one bleed, and it is also effective for CCMs causing therapy resistant
      epilepsy especially if applied within 3 years after presentation. In modern SRS
      series the rate of persisting adverse radiation effects is low, resulting only in
      mild morbidity even in deep-seated lesions (4.16%, N.=376), and morbidity caused
      by post-treatment hemorrhages is also low (5.3%, N.=132). Admittedly, there is no
      high quality evidence to define the relative roles of microsurgery, SRS and wait
      and-see policy in the management of detected CCMs at present. However, based on
      increasing positive experience, we recommend early SRS soon after presentation in
      neurologically intact or minimally disabled patients harboring deep-seated CCMs,
      because waiting for the cumulative morbidity of the natural history to justify an
      otherwise low-risk intervention does not serve the patient well. 

PMID- 25968928
TI  - Neuroimaging of cerebral cavernous malformations.
AB  - Cerebral cavernous malformations (CCMs) are vascular malformations of the brain
      and brainstem that arise via a number of different mechanisms and can result in
      non-specific presentations. Therefore, medical imaging is essential in the
      diagnosis of these lesions and important to guide their clinical or surgical
      management. MRI is the modality of choice with newer protocols, such as
      susceptibility weighted imaging, playing an increasingly important role in the
      detection of CCMs. In this review we will discuss lesion structure, its proposed
      origins, and common lesion presentations and complications, before covering their
      expected appearances with different imaging modalities. We conclude with a
      discussion of insights about lesion behaviour acquired from advanced imaging
      techniques and provide a general approach to characterizing and diagnosing CCM
      lesions with neuroimaging. 

PMID- 25968929
TI  - The prevalence of anti-K in Canadian prenatal patients.
AB  - BACKGROUND: Anti-KEL1(K) is a major cause of hemolytic disease of the fetus and
      newborn. We utilized data from prenatal testing of patients in Western Canada to
      determine the frequency of anti-K. In Manitoba, we evaluated the frequency of
      transfusion as the likely cause for alloimmunization. We reviewed international
      practices to prevent alloimmunization. STUDY DESIGN AND METHODS: Prenatal
      patients undergo antibody screening using an automated testing platform and
      uniform testing algorithm. Data on the frequency of antibodies, transfusion
      history, and donor K typing were extracted from the relevant databases at
      Canadian Blood Services. National standards were reviewed with the help of local
      experts. RESULTS: Anti-K was found in 397 of 390,193 patients from 2011 to 2013
      (1.02 per 1000) and was the second most frequent antibody after anti-E. In
      Manitoba, 26 of 75 (35%) anti-K patients had received transfusions in the
      province since 2001; 14 of the 26 (54%) had received at least one K+ RBC unit and
      three had received all K- units, while in nine, donor K typing was incomplete.
      Only eight of the 26 had previous pregnancies, three with K+ partners.
      International practice varies; however, prophylactic use of matched or K- units
      is standard in many European countries. CONCLUSIONS: Anti-K was found in 0.1% of
      prenatal patients. Although our data on the history of transfusion are
      incomplete, they demonstrate that transfusion with a K+ unit is a major cause of
      alloimmunization. Given advances in phenotyping and genotyping technologies,
      prophylactic matching should be considered in Canada.

PMID- 25968930
TI  - Diquafosol ophthalmic solution 3 %: a review of its use in dry eye.
AB  - Diquafosol ophthalmic solution 3 % (Diquas((r))) is a P2Y2 receptor agonist that
      promotes tear fluid and mucin secretion and is currently approved in Japan and
      South Korea for the treatment of dry eye. In randomized, double-blind,
      multicentre trials in patients with dry eye, significantly greater improvements
      in fluorescein and rose bengal staining scores were seen with diquafosol
      ophthalmic solution 3 % than with placebo, and diquafosol ophthalmic solution 3 %
      was noninferior to sodium hyaluronate ophthalmic solution 0.1 % in terms of the
      improvement in the fluorescein staining score and more effective than sodium
      hyaluronate ophthalmic solution 0.1 % in terms of the improvement in the rose
      bengal staining score. The efficacy of diquafosol ophthalmic solution 3 % in the
      treatment of dry eye was maintained in the longer term, with improvements also
      seen in subjective dry eye symptoms, and was also shown in a real-world setting.
      Diquafosol ophthalmic solution 3 % also demonstrated efficacy in various specific
      dry eye disorders, including aqueous-deficient dry eye, short tear film break-up
      time dry eye, obstructive meibomian gland dysfunction, dry eye following laser in
      situ keratomileusis surgery and dry eye following cataract surgery, as well as in
      contact lens wearers and visual display terminal users. Diquafosol ophthalmic
      solution 3 % was generally well tolerated in patients with dry eye, with eye
      irritation the most commonly reported adverse event. In conclusion, diquafosol
      ophthalmic solution 3 % is a useful option for the treatment of dry eye.

PMID- 25968931
TI  - Preventive Cardiology Update: Controversy, Consensus, and Future Promise.

PMID- 25968932
TI  - High-Density Lipoprotein Function Measurement in Human Studies: Focus on
      Cholesterol Efflux Capacity.
AB  - A low plasma level of high-density lipoprotein (HDL) cholesterol (HDL-C) is a
      major risk factor for the development of atherosclerotic cardiovascular disease
      (ASCVD). However, several observations have highlighted the shortcomings of using
      cholesterol content as the sole reflection of HDL metabolism. In particular,
      several large randomized controlled trials of extended release niacin and
      cholesteryl-ester transfer protein (CETP) inhibitors on background statin therapy
      have failed to show improvement in ASCVD outcomes despite significant increases
      in HDL-C. Reverse cholesterol transport (RCT) is the principal HDL function that
      impacts macrophage foam cell formation and other functions such as endothelial
      activation of endothelial nitric oxide synthase, monocyte adhesion, and platelet
      aggregation. Cholesterol efflux from macrophages to plasma/serum reflects the
      first critical step of RCT and is considered a key anti-atherosclerotic function
      of HDL. Whether this function is operative in humans remains to be seen, but
      recent studies assessing cholesterol efflux in humans suggest that the
      cholesterol efflux capacity (CEC) of human plasma or serum is a potent marker of
      ASCVD risk. This review describes the methodology of measuring CEC ex vivo from
      human samples and the findings to date linking CEC to human disease. Studies to
      date confirm that CEC can be reliably measured using stored human blood samples
      as cholesterol acceptors and suggest that CEC may be a promising new biomarker
      for atherosclerotic and metabolic diseases. Further studies are needed to
      standardize measurements and clarify the role CEC may play in predicting risk of
      developing disease and response to therapies. 

PMID- 25968933
TI  - Mussel-Inspired Protein Nanoparticles Containing Iron(III)-DOPA Complexes for pH
      Responsive Drug Delivery.
AB  - A novel bioinspired strategy for protein nanoparticle (NP) synthesis to achieve
      pH-responsive drug release exploits the pH-dependent changes in the coordination
      stoichiometry of iron(III)-3,4-dihydroxyphenylalanine (DOPA) complexes, which
      play a major cross-linking role in mussel byssal threads. Doxorubicin-loaded
      polymeric NPs that are based on Fe(III)-DOPA complexation were thus synthesized
      with a DOPA-modified recombinant mussel adhesive protein through a co
      electrospraying process. The release of doxorubicin was found to be predominantly
      governed by a change in the structure of the Fe(III)-DOPA complexes induced by an
      acidic pH value. It was also demonstrated that the fabricated NPs exhibited
      effective cytotoxicity towards cancer cells through efficient cellular uptake and
      cytosolic release. Therefore, it is anticipated that Fe(III)-DOPA complexation
      can be successfully utilized as a new design principle for pH-responsive NPs for
      diverse controlled drug-delivery applications.

PMID- 25968934
TI  - Neuroplasticity subserving the operation of brain-machine interfaces.
AB  - Neuroplasticity is key to the operation of brain machine interfaces (BMIs)-a
      direct communication pathway between the brain and a man-made computing device.
      Whereas exogenous BMIs that associate volitional control of brain activity with
      neurofeedback have been shown to induce long lasting plasticity, endogenous BMIs
      that use prolonged activity-dependent stimulation--and thus may curtail the time
      scale that governs natural sensorimotor integration loops--have been shown to
      induce short lasting plasticity. Here we summarize recent findings from studies
      using both categories of BMIs, and discuss the fundamental principles that may
      underlie their operation and the longevity of the plasticity they induce. We draw
      comparison to plasticity mechanisms known to mediate natural sensorimotor skill
      learning and discuss principles of homeostatic regulation that may constrain
      endogenous BMI effects in the adult mammalian brain. We propose that BMIs could
      be designed to facilitate structural and functional plasticity for the purpose of
      re-organization of target brain regions and directed augmentation of sensorimotor
      maps, and suggest possible avenues for future work to maximize their efficacy and
      viability in clinical applications.

PMID- 25968936
TI  - Preliminary insights into the incorporation of rosemary extract (Rosmarinus
      officinalis L.) in fish feed: influence on performance and physiology of gilthead
      seabream (Sparus aurata).
AB  - Gilthead seabream (Sparus aurata) were fed a basal (control) diet and four
      experimental diets (R600, R1200, R1800 and R2400), containing 600, 1200, 1800 and
      2400 mg kg(-1), respectively, of rosemary extract (Rosmarinus officinalis L.). At
      4 and 12 weeks from the beginning of the ongrowing period, the fish were
      sacrificed, blood was drawn to obtain plasma and the liver and intestines were
      dissected. Growth and feed intake were unaffected by rosemary extract addition. A
      histological examination of the intestine revealed no differences among the
      dosages, while the liver showed a sharp decrease in hepatic steatosis in diets
      supplemented with rosemary extract. Furthermore, plasma alanine aminotransferase
      was lower with these diets at the end of the ongrowing period. Rosemary extract
      reduced the plasma levels of glucose and triglycerides on week 4 and glucose and
      HDL/LDL cholesterol ratio on week 12, suggesting better transport and energy
      metabolism of the lipids. Overall, the most evident effect of rosemary extract
      was observed with the 600 mg kg(-1) dose. 

PMID- 25968937
TI  - Association between Apolipoprotein E Variants and Obesity-Related Traits in
      Mexican School Children.
AB  - BACKGROUND/AIM: Genetic variation in apolipoprotein E (ApoE) has a key role in
      lipid metabolism. However, its contribution to the amount and distribution of
      body fat is under investigation. The aim of this study was to analyze the
      association between genetic variation in ApoE and obesity-related traits in
      Mexican school children. MATERIAL AND METHODS: Anthropometric, body composition
      and physical activity measures were conducted using standard methods in 300
      children (177 girls/123 boys) who fulfilled the inclusion criteria. DNA was
      isolated from saliva. ApoE genotypes were analyzed by allelic discrimination. The
      association between variation in ApoE and anthropometric and body composition
      measures was investigated using the General Linear Model. RESULTS: The mean+/-SD
      values for age, body mass index (BMI) and waist circumference (WC) were 9.05+/
      0.80 years, 19.01+/-3.83 and 67.98+/-10.97 cm, respectively. Approximately 46% of
      the participants were overweight or obese. A significant association between ApoE
      isoforms and WC was found after controlling for age, sex and the percentage of
      physical activity (p=0.025). Significant main effects were found for vigorous
      physical activity and light physical activity influencing the adiposity-related
      BMI (p<0.001) and WC (p=0.044), respectively. CONCLUSIONS: Variation in ApoE and
      physical activity intensity were associated with adiposity-related phenotypes in
      Mexican school children.

PMID- 25968938
TI  - Mitochondrial Src tyrosine kinase plays a role in the cardioprotective effect of
      ischemic preconditioning by modulating complex I activity and mitochondrial ROS
      generation.
AB  - While ischemic preconditioning (IPC) and other cardioprotective interventions
      have been proposed to protect the heart from ischemia/reperfusion (I/R) injury by
      inhibiting mitochondrial complex I activity upon reperfusion, the exact mechanism
      underlying the modulation of complex I activity remains elusive. This study was
      aimed to test the hypothesis that IPC modulates complex I activity at reperfusion
      by activating mitochondrial Src tyrosine kinase, and induces cardioprotection
      against I/R injury. Isolated rat hearts were preconditioned by three cycles of 5
      min ischemia and 5-min reperfusion prior to 30-min index ischemia followed by 2 h
      of reperfusion. Mitochondrial Src phosphorylation (Tyr(416)) was dramatically
      decreased during I/R, implying inactivation of Src tyrosine kinase by I/R. IPC
      increased mitochondrial Src phosphorylation upon reperfusion and this was
      inhibited by the selective Src tyrosine kinase inhibitor PP2. IPC's anti-infarct
      effect was inhibited by the selective Src tyrosine kinase inhibitor PP2. Complex
      I activity was significantly increased upon reperfusion, an effect that was
      prevented by IPC in a Src tyrosine kinase-dependent manner. In support, Src and
      phospho-Src were found in complex I. Furthermore, IPC prevented
      hypoxia/reoxygenation-induced mitochondrial reactive oxygen species (ROS)
      generation and cellular injury in rat cardiomyocytes, which was revoked by PP2.
      Finally, IPC reduced LDH release induced by both hypoxia/reoxygenation and
      simulated ischemia/reperfusion, an effect that was reversed by PP2 and Src siRNA.
      These data suggest that mitochondrial Src tyrosine kinase accounts for the
      inhibitory action of IPC on complex I and mitochondrial ROS generation, and
      thereby plays a role in the cardioprotective effect of IPC. 

PMID- 25968935
TI  - Pathogenesis and new candidate treatments for infantile spasms and early life
      epileptic encephalopathies: A view from preclinical studies.
AB  - Early onset and infantile epileptic encephalopathies (EIEEs) are usually
      associated with medically intractable or difficult to treat epileptic seizures
      and prominent cognitive, neurodevelopmental and behavioral consequences. EIEEs
      have numerous etiologies that contribute to the inter- and intra-syndromic
      phenotypic variability. Etiologies include structural and metabolic or genetic
      etiologies although a significant percentage is of unknown cause. The need to
      better understand their pathogenic mechanisms and identify better therapies has
      driven the development of animal models of EIEEs. Several rodent models of
      infantile spasms have emerged that recapitulate various aspects of the disease.
      The acute models manifest epileptic spasms after induction and include the NMDA
      rat model, the NMDA model with prior prenatal betamethasone or perinatal stress
      exposure, and the gamma-butyrolactone induced spasms in a mouse model of Down
      syndrome. The chronic models include the tetrodotoxin rat model, the aristaless
      related homeobox X-linked (Arx) mouse models and the multiple-hit rat model of
      infantile spasms. We will discuss the main features and findings from these
      models on target mechanisms and emerging therapies. Genetic models have also
      provided interesting data on the pathogenesis of Dravet syndrome and proposed new
      therapies for testing. The genetic associations of many of the EIEEs have also
      been tested in rodent models as to their pathogenicity. Finally, several models
      have tested the impact of subclinical epileptiform discharges on brain function.
      The impact of these advances in animal modeling for therapy development will be
      discussed. 

PMID- 25968939
TI  - Neuroprotective effects of ginkgetin against neuroinjury in Parkinson's disease
      model induced by MPTP via chelating iron.
AB  - Disruption of neuronal iron homeostasis and oxidative stress are closely related
      to the pathogenesis of Parkinson's disease (PD). Ginkgetin, a natural biflavonoid
      isolated from leaves of Ginkgo biloba L, has many known effects, including anti
      inflammatory, anti-influenza virus, and anti-fungal activities, but its
      underlying mechanism of the neuroprotective effects in PD remains unclear. The
      present study utilized PD models induced by 1-methyl-4-phenylpyridinium (MPP(+))
      and 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) to explore the
      neuroprotective ability of ginkgetin in vivo and in vitro. Our results showed
      that ginkgetin could provide significant protection from MPP(+)-induced cell
      damage in vitro by decreasing the levels of intracellular reactive oxygen species
      and maintaining mitochondrial membrane potential. Meanwhile, ginkgetin
      dramatically inhibited cell apoptosis induced by MPP+ through the caspase-3 and
      Bcl2/Bax pathway. Moreover, ginkgetin significantly improved sensorimotor
      coordination in a mouse PD model induced by MPTP by dramatically inhibiting the
      decrease of tyrosine hydroxylase expression in the substantia nigra and
      superoxide dismutase activity in the striatum. Interestingly, ginkgetin could
      strongly chelate ferrous ion and thereby inhibit the increase of the
      intracellular labile iron pool through downregulating L-ferritin and upregulating
      transferrin receptor 1. These results indicate that the neuroprotective mechanism
      of ginkgetin against neurological injury induced by MPTP occurs via regulating
      iron homeostasis. Therefore, ginkgetin may provide neuroprotective therapy for PD
      and iron metabolism disorder related diseases. 

PMID- 25968940
TI  - Arctigenin suppresses transforming growth factor-beta1-induced expression of
      monocyte chemoattractant protein-1 and the subsequent epithelial-mesenchymal
      transition through reactive oxygen species-dependent ERK/NF-kappaB signaling
      pathway in renal tubular epithelial cells.
AB  - Transforming growth factor-beta1 (TGF-beta1) induces expression of the
      proinflammatory and profibrotic cytokine monocyte chemoattractant protein-1 (MCP
      1) in tubular epithelial cells (TECs) and thereby contributes to the tubular
      epithelial-mesenchymal transition (EMT), which in turn leads to the progression
      of tubulointerstitial inflammation into tubulointerstitial fibrosis. Exactly how
      TGF-beta1 causes MCP-1 overexpression and subsequent EMT is not well understood.
      Using human tubular epithelial cultures, we found that TGF-beta1 upregulated the
      expression of reduced nicotinamide adenine dinucleotide phosphate oxidases 2 and
      4 and their regulatory subunits, inducing the production of reactive oxygen
      species. These reactive species activated a signaling pathway mediated by
      extracellular signal-regulated kinase (ERK1/2) and nuclear factor-kappaB (NF
      kappaB), which upregulated expression of MCP-1. Incubating cultures with TGF
      beta1 was sufficient to induce hallmarks of EMT, such as downregulation of
      epithelial marker proteins (E-cadherin and zonula occludens-1), induction of
      mesenchymal marker proteins (alpha-smooth muscle actin, fibronectin, and
      vimentin), and elevated cell migration and invasion in an EMT-like manner.
      Overexpressing MCP-1 in cells exposed to TGF-beta1 exacerbated these EMT-like
      changes. Pretreating cells with the antioxidant and anti-inflammatory compound
      arctigenin (ATG) protected them against these TGF-beta1-induced EMT-like changes;
      the compound worked by inhibiting the ROS/ERK1/2/NF-kappaB pathway to decrease
      MCP-1 upregulation. These findings suggest ATG as a new therapeutic candidate to
      inhibit or even reverse tubular EMT-like changes during progression to
      tubulointerstitial fibrosis, and they provide the first clues to how ATG may
      work. 

PMID- 25968942
TI  - Special issue on "Peroxidase".

PMID- 25968941
TI  - Ultrasensitive UPLC-MS/MS method for analysis of etheno-DNA adducts in human
      white blood cells.
AB  - Etheno-DNA adducts are generated by interaction of cellular DNA with exogenous
      environmental carcinogens and end products of lipid peroxidation. It has been
      determined that 1,N(6)-etheno-2'-deoxyadenosine (epsilondA) and 3,N(4)-etheno-2'
      deoxycytidine (epsilondC) adducts formed in human white blood cells can be used
      to serve as biomarkers of genetic damage mediated by oxidative stress. In this
      study, we developed an ultrasensitive ultra-performance liquid chromatography
      tandem mass spectrometry (UPLC-MS/MS) method used to detect and quantify
      epsilondA and dC adducts in human white blood cells. The percent recoveries of
      epsilondA and dC adducts were found to be 88.9% +/- 2.8 and 95.7% +/- 3.7,
      respectively. The detection limits were ~ 1.45 fmol for epsilondA and ~ 1.27 fmol
      for epsilondC in 20 MUg of human white blood cell DNA samples, both epsilondA and
      epsilondC adducts could be detected using only ~ 5 MUg of DNA per sample. For
      validation of the method, 34 human blood cell DNA samples were assayed and the
      results revealed a significant difference (P < 0.01) between levels (fmol/MUg
      DNA) of 0.82 +/- 0.83 (standard deviation [SD]) (range: 0.15-3.11) for epsilondA,
      3.28 +/- 3.15 (SD) (range: 0.05-9.6) for epsilondC in benzene-exposed workers;
      and 0.04 +/- 0.08 (SD) (range: 0.0-0.27) for epsilondA and 0.77 +/- 1.02 (SD)
      (range: 0.10-4.11) for epsilondC in non-benzene-exposed workers. Our method shows
      a high sensitivity and specificity when applied to small amounts of human white
      blood cell DNA samples; background levels of epsilondA and epsilondC could be
      reproducibly detected. The ultrasensitive and simple detection method is thus
      suitable for applications in human biomonitoring and molecular epidemiology
      studies.

PMID- 25968943
TI  - Fructose-induced ROS generation impairs glucose utilization in L6 skeletal muscle
      cells.
AB  - High fructose consumption has implicated in insulin resistance and metabolic
      syndrome. Fructose is a highly lipogenic sugar that has intense metabolic effects
      in liver. Recent evidences suggest that fructose exposure to other tissues has
      substantial and profound metabolic consequences predisposing toward chronic
      conditions such as type 2 diabetes. Since skeletal muscle is the major site for
      glucose utilization, in the present study we define the effects of fructose
      exposure on glucose utilization in skeletal muscle cells. Upon fructose exposure,
      the L6 skeletal muscle cells displayed diminished glucose uptake, glucose
      transporter type 4 (GLUT4) translocation, and impaired insulin signaling. The
      exposure to fructose elevated reactive oxygen species (ROS) production in L6
      myotubes, accompanied by activation of the stress/inflammation markers c-Jun N
      terminal kinase (JNK) and extracellular signal-regulated kinase 1/2 (ERK1/2), and
      degradation of inhibitor of NF-kappaB (IkappaBalpha). We found that fructose
      caused impairment of glucose utilization and insulin signaling through ROS
      mediated activation of JNK and ERK1/2 pathways, which was prevented in the
      presence of antioxidants. In conclusion, our data demonstrate that exposure to
      fructose induces cell-autonomous oxidative response through ROS production
      leading to impaired insulin signaling and attenuated glucose utilization in
      skeletal muscle cells. 

PMID- 25968944
TI  - Oxidative stress and mitochondrial dysfunction play a role in myelodysplastic
      syndrome development, diagnosis, and prognosis: A pilot study.
AB  - The imbalance between reactive oxygen species (ROS) production and their
      elimination by antioxidants leads to oxidative stress. Depending on their
      concentration, ROS can trigger apoptosis or stimulate cell proliferation. We
      hypothesized that oxidative stress and mitochondrial dysfunction may participate
      not only in apoptosis detected in some myelodysplastic syndrome (MDS) patients,
      but also in increasing proliferation in other patients. We investigated the
      involvement of oxidative stress and mitochondrial dysfunction in MDS
      pathogenesis, as well as assessed their diagnostic and prognostic values.
      Intracellular peroxides, superoxide, superoxide/peroxides ratio, reduced
      glutathione (GSH), and mitochondrial membrane potential (Deltapsi(mit)) levels
      were analyzed in bone marrow cells from 27 MDS patients and 12 controls, by flow
      cytometry. We observed that all bone marrow cell types from MDS patients had
      increased intracellular peroxide levels and decreased GSH content, compared with
      control cells. Moreover, oxidative stress levels were MDS subtype- and risk group
      dependent. Low-risk patients had the highest ROS levels, which can be related
      with their high apoptosis; and intermediate-2-risk patients had high
      Deltapsi(mit) that may be associated with their proliferative potential. GSH
      levels were negatively correlated with transfusion dependency, and peroxide
      levels were positively correlated with serum ferritin level. GSH content proved
      to be an accurate parameter to discriminate patients from controls. Finally,
      patients with high ROS or low GSH levels, as well as high superoxide/peroxides
      ratio had lower overall survival. Our results suggest that oxidative stress and
      mitochondrial dysfunction are involved in MDS development, and that oxidative
      stress parameters may constitute novel diagnosis and/or prognosis biomarkers for
      MDS.

PMID- 25968945
TI  - Covalent modification of DNA by alpha, beta-unsaturated aldehydes derived from
      lipid peroxidation: Recent progress and challenges.
AB  - Oxidative stress-induced lipid peroxidation (LPO) has been associated with human
      physiology and pathophysiology. LPO generates an array of oxidation products and
      among them reactive lipid aldehydes have received intensive research attentions
      due to their roles in modulating functions of biomolecules through covalent
      modification. Thus, covalent modification of DNA by these reactive lipid
      electrophiles has been postulated to be partially responsible for the biological
      roles of LPO. In this review, we summarized recent progress and challenges in
      studying the roles of covalent modification of DNA including nuclear and
      mitochondrial DNA by reactive lipid metabolites from LPO. We focused on the novel
      mechanistic insights into generation of lipid aldehydes from cellular membranes
      especially mitochondria through LPO. Recent advances in the technological front
      using mass spectrometry have also been highlighted in the settings of studying
      DNA damage caused by LPO and its biological relevance. 

PMID- 25968946
TI  - Antagonistic pleiotropic effects of nitric oxide in the pathophysiology of
      Parkinson's disease.
AB  - Sporadic Parkinson's disease (PD) is a geriatric disorder with unknown etiology,
      specifically affecting the nigrostriatal dopaminergic (DA-ergic) pathway of the
      brain. Amongst several contributing factors, nitric oxide (NO*) is considered to
      inflict injury to DA-ergic neurons, and to influence PD progression. Supportive
      evidence for this comes from animal models of PD, where inhibitors of NO*
      synthase (NOS) are found to protect against DA-ergic neuronal death, and NOS
      deficient mice are found to be resistant to PD-producing neurotoxins. Presence of
      nitrated proteins and upregulated levels of NOS in human postmortem PD brain
      samples have rendered further support to this contention. While NO* from neuronal
      NOS contributes to neurodegeneration in PD, NO* produced by inducible NOS from
      proliferating microglia as inflammatory responses to neuronal insults are
      suggested to mediate the disease progression. Another view that NO* in small
      doses serves as a neuroprotective agent in the brain is also discussed, in light
      of experimental evidence available in vitro and in vivo. This view is based on
      the argument that NO* could form harmless nitrites and nitrates on reaction with
      endogenously produced reactive oxygen species (ROS) within the cells. This review
      essentially discusses the possibilities of considering NO* as a secondary
      response of DA-ergic cell death, while oxidative stress is the primary cause.
      Once neurons undergo death processes following uncontrolled oxidative insult, the
      resulting gliosis-mediated NO* accelerates the events as a secondary mediator.
      Since the time of initiation of DA-ergic cell death cannot be predicted, NO*
      could be an ideal molecular target to halt the disease progression. 

PMID- 25968947
TI  - An immunological method to combine the measurement of active and total
      myeloperoxidase on the same biological fluid, and its application in finding
      inhibitors which interact directly with the enzyme.
AB  - Myeloperoxidase (MPO) is a pro-oxidant enzyme involved in inflammation, and the
      measurement of its activity in biological samples has emerged essential for
      laboratory and clinical investigations. We will describe a new method which
      combines the SIEFED (specific immunological extraction followed by enzymatic
      detection) and ELISA (ELISAcb) techniques to measure the active and total amounts
      of MPO on the same human sample and with the same calibration curve, as well as
      to define an accurate ratio between both the active and total forms of the
      enzyme. The SIEFED/ELISAcb method consists of the MPO extraction from aqueous or
      biological samples by immobilized anti-MPO antibodies coated onto microplate
      wells. After a washing step to eliminate unbound material, the activity of MPO is
      measured in situ by adding a reaction solution (SIEFED). Following aspiration of
      the reaction solution, a secondary anti-MPO antibody is added into the wells and
      the ELISAcb test is carried out in order to measure the total MPO content. To
      validate the combined method, a comparison was made with SIEFED and ELISA
      experiments performed separately on plasma samples isolated from human whole
      blood, after a neutrophil stimulation. The SIEFED/ELISAcb provides a suitable
      tool for the measurement of specific MPO activity in biological fluids and for
      the estimation of the inhibitory potential of a fluid. The method can also be
      used as a pharmacological tool to make the distinction between a catalytic
      inhibitor, which binds to MPO and inhibits its activity, and a steric inhibitor,
      which hinders the enzyme and prevents its immunodetection. 

PMID- 25968948
TI  - Insulin protects H9c2 rat cardiomyoblast cells against hydrogen peroxide-induced
      injury through upregulation of microRNA-210.
AB  - BACKGROUND: Insulin protects cardiomyocytes from reactive oxygen species (ROS)
      induced apoptosis after ischemic/reperfusion injury, but the mechanism is not
      clear. This study investigated the protective mechanism of insulin in preventing
      cardiomyocyte apoptosis from ROS injury. METHODS: Rat cardiomyoblast H9c2 cells
      were treated with hydrogen peroxide (H2O2) or insulin at various concentrations
      for various periods of time, or with insulin and H2O2 for various periods of
      time. Cell viability was measured by the methylthiazolydiphenyl-tetrazolium
      bromide method. Cellular miR-210 levels were quantified using real-time RT-PCR.
      MiR-210 expression was also manipulated through lentivirus-mediated transfection.
      LY294002 was used to investigate involvement of the phosphatidylinositol 3-kinase
      (PI3K)/Akt pathway. RESULTS: The percentage of viable cells was significantly and
      inversely associated with H2O2 concentration, an effect that was seemingly
      attenuated by insulin pretreatment. Treatments with H2O2 or insulin were
      associated with a significant increase in miR-210 levels. Manipulation of miR-210
      expression by gene transfection showed that miR-210 could attenuate H2O2-induced
      cellular injury. Inhibition of the PI3K/Akt pathway by the Akt inhibitor LY294002
      was associated with a decrease in miR-210 expression. CONCLUSION: Insulin
      stimulated the expression of miR-210 through the PI3K/Akt pathway, resulting in a
      protective effect against cardiomyocyte injury that had been induced by
      H2O2/oxygen species. Our results provide novel evidence regarding the mechanism
      underlying the protective effect of insulin.

PMID- 25968950
TI  - Aldehyde adducts generated during lipid peroxidation modification of proteins.
AB  - Various lines of evidence indicate that an important part in the pathogenesis of
      atherosclerosis is the modification of the plasma low-density lipoproteins
      (LDLs). A large number of pro-inflammatory and pro-atherogenic properties have
      been ascribed to the oxidatively modified LDLs and their components. There is
      considerable evidence to support the role of lipid peroxidation products,
      reactive aldehydes in particular, originating from the oxidized LDL as important
      signaling molecules in the context of the atherosclerotic lesion. These aldehydes
      generated during the peroxidation of LDL exhibit a facile reactivity with
      proteins, generating a variety of intra- and intermolecular covalent adducts on
      the apolipoprotein B-100 particle in LDL. Characterization of the aldehyde
      adducts generated in the protein is therefore critical in understanding the
      nature of the oxidized LDL. However, the majority of adducts generated during the
      oxidative modification of LDL have not yet been chemically characterized. In this
      review, the current status of aldehyde adducts quantitatively analyzed in the
      Cu(2+)-oxidized LDL is reviewed. 

PMID- 25968949
TI  - Medium-throughput ESR detection of superoxide production in undetached adherent
      cells using cyclic nitrone spin traps.
AB  - Spin trapping with cyclic nitrones coupled to electron spin resonance (ESR) is
      recognized as a specific method of detection of oxygen free radicals in
      biological systems, especially in culture cells. In this case, the detection is
      usually performed on cell suspensions, which is however unsuitable when adhesion
      influences free radical production. Here, we performed ESR detection of
      superoxide with four spin traps (5-diethoxyphosphoryl-5-methyl-1-pyrroline N
      oxide, DEPMPO; 5-diisopropoxyphosphoryl-5-methyl-1-pyrroline N-oxide, DIPPMPO;
      (4R*, 5R*)-5-(diisopropyloxyphosphoryl)-5-methyl-4-[({[2
      (triphenylphosphonio)ethyl]carbamoyl}oxy)methyl]pyrroline N-oxide bromide, Mito
      DIPPMPO; and 6-monodeoxy-6-mono-4-[(5-diisopropoxyphosphoryl-5-methyl-1-pyrroline
      N-oxide)-ethylenecarbamoyl-(2,3-di-O-methyl) hexakis (2,3,6-tri-O-methyl)]-beta
      cyclodextrin, CD-DIPPMPO) directly on RAW 264.7 macrophages cultured on
      microscope coverslip glasses after phorbol 12-myristate 13-acetate (PMA)
      stimulation. Distinct ESR spectra were obtained with each spin trap using this
      method. CD-DIPPMPO, a recently published phosphorylated cyclic nitrone bearing a
      permethylated beta-cyclodextrin moiety, was confirmed as the most specific spin
      trap of the superoxide radical, with exclusive detection of the superoxide
      adduct. ESR detection performed on cells attached to coverslips represents
      significant advances over other methods in terms of simplicity, speed, and
      measurement under near-physiological conditions. It thus opens the way for
      numerous applications, such as medium-throughput screening of antioxidants and
      reactive oxygen species (ROS)-modulating agents. 

PMID- 25968951
TI  - In vivo targeted molecular magnetic resonance imaging of free radicals in
      diabetic cardiomyopathy within mice.
AB  - Free radicals contribute to the pathogenesis of diabetic cardiomyopathy. We
      present a method for in vivo observation of free radical events within murine
      diabetic cardiomyopathy. This study reports on in vivo imaging of protein/lipid
      radicals using molecular MRI (mMRI) and immuno-spin trapping (IST) in diabetic
      cardiac muscle. To detect free radicals in diabetic cardiomyopathy,
      streptozotocin (STZ)-exposed mice were given 5,5-dimethyl-pyrroline-N-oxide
      (DMPO) and administered an anti-DMPO probe (biotin-anti-DMPO antibody-albumin-Gd
      DTPA). For controls, non-diabetic mice were given DMPO (non-disease control), and
      administered an anti-DMPO probe; or diabetic mice were given DMPO but
      administered a non-specific IgG contrast agent instead of the anti-DMPO probe.
      DMPO administration started at 7 weeks following STZ treatment for 5 days, and
      the anti-DMPO probe was administered at 8 weeks for MRI detection. MRI was used
      to detect a significant increase (p < 0.001) in MRI signal intensity (SI) from
      anti-DMPO nitrone adducts in diabetic murine left-ventricular (LV) cardiac
      tissue, compared to controls. Regional increases in MR SI in the LV were found in
      the apical and upper-left areas (p < 0.01 for both), compared to controls. The
      biotin moiety of the anti-DMPO probe was targeted with fluorescently-labeled
      streptavidin to locate the anti-DMPO probe in excised cardiac tissues, which
      indicated elevated fluorescence only in cardiac muscle of mice administered the
      anti-DMPO probe. Oxidized lipids and proteins were also found to be significantly
      elevated (p < 0.05 for both) in diabetic cardiac muscle compared to controls. It
      can be concluded that diabetic mice have more heterogeneously distributed
      radicals in cardiac tissue than non-diabetic mice. 

PMID- 25968952
TI  - Analysis of the oxidative damage of DNA, RNA, and their metabolites induced by
      hyperglycemia and related nephropathy in Sprague Dawley rats.
AB  - We used a sensitive and accurate method based on isotope dilution high
      performance liquid chromatography-triple quadrupole mass spectrometry (ID-LC
      MS/MS) to determine the levels of 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxo-dGsn)
      and 8-oxo-7,8-dihydroguanosin (8-oxo-Gsn) in various tissue specimens, plasma,
      and urine of hyperglycemic Sprague Dawley rats induced by streptozotocin (STZ).
      The oxidative DNA and RNA damages were observed in various organs and the amounts
      of 8-oxo-dGsn and 8-oxo-Gsn derived from DNA and RNA were increased with
      hyperglycemic status. In contrast to the results of the nucleic acid samples
      derived from tissues, the levels of 8-oxo-Gsn in urine and plasma were
      significantly higher compared with that of 8-oxo-dGsn, which most likely
      reflected the RNA damage that occurs more frequently compared with DNA damage.
      For the oxidative stress induced by hyperglycemia, 8-oxo-Gsn in urine may be a
      sensitive biomarker on the basis of the results in urine, plasma, and tissues. In
      addition, high levels of urinary 8-oxo-Gsn were observed before diabetic
      microvascular complications. Based on that the 8-oxo-dGsn was associated with
      diabetic nephropathy and RNA was more vulnerable to oxidative stress compared
      with DNA. We also propose that 8-oxo-Gsn is correlated with diabetic nephropathy
      and that 8-oxo-Gsn in urine could be a useful and sensitive marker of diabetic
      nephropathy.

PMID- 25968953
TI  - Brain imaging in methamphetamine-treated mice using a nitroxide contrast agent
      for EPR imaging of the redox status and a gadolinium contrast agent for MRI
      observation of blood-brain barrier function.
AB  - Methamphetamine (METH)-induced neurotoxicity is associated with mitochondrial
      dysfunction and enhanced oxidative stress. The aims of the present study
      conducted in the mouse brain repetitively treated with METH were to (1) examine
      the redox status using the redox-sensitive imaging probe 3-methoxycarbonyl
      2,2,5,5-tetramethylpiperidine-1-oxyl (MCP) and (2) non-invasively visualize the
      brain redox status with electron paramagnetic resonance (EPR) imaging. The rate
      of reduction of MCP was measured from a series of temporal EPR images of mouse
      heads, and this rate was used to construct a two-dimensional map of rate
      constants called a "redox map." The obtained redox map clearly illustrated the
      change in redox balance in the METH-treated mouse brain that is a known result of
      oxidative damage. Biochemical assays also showed that the level of thiobarbituric
      acid-reactive substance, an index of lipid peroxidation, was increased in mouse
      brains by METH. The enhanced reduction in MCP observed in mouse brains was
      remarkably suppressed by treatment with the dopamine synthase inhibitor, alpha
      methyl-p-tyrosine, suggesting that enhancement of the reduction reaction of MCP
      resulted from enzymatic reduction in the mitochondrial respiratory chain.
      Furthermore, magnetic resonance imaging (MRI) of METH-treated mice using a blood
      brain barrier (BBB)-impermeable paramagnetic contrast agent revealed BBB
      dysfunction after treatment with METH for 7 days. MRI also indicated that the
      impaired BBB recovered after withdrawal of METH. EPR imaging and MRI are useful
      tools not only for following changes in the redox status and BBB dysfunction in
      mouse brains repeatedly administered METH, but also for tracing the drug effect
      after withdrawal of METH. 

PMID- 25968954
TI  - Antioxidant metallothionein alleviates endoplasmic reticulum stress-induced
      myocardial apoptosis and contractile dysfunction.
AB  - AIMS: Endoplasmic reticulum (ER) stress exerts myocardial oxidative stress,
      apoptosis, and contractile anomalies, although the precise interplay between ER
      stress and apoptosis remains elusive. This study was designed to examine the
      impact of the cysteine-rich free radical scavenger metallothionein on ER stress
      induced myocardial contractile defect and underlying mechanisms. METHODS AND
      RESULTS: Wild-type friendly virus B and transgenic mice with cardiac-specific
      overexpression of metallothionein were challenged with the ER stress inducer
      tunicamycin (1 mg/kg, intraperitoneal, 48 h) prior to the assessment of
      myocardial function, oxidative stress, and apoptosis. Our results revealed that
      tunicamycin promoted cardiac remodeling (enlarged left ventricular end
      systolic/diastolic diameters with little changes in left ventricular wall
      thickness), suppressed fractional shortening and cardiomyocyte contractile
      function, elevated resting Ca(2+), decreased stimulated Ca(2+) release, prolonged
      intracellular Ca(2+) clearance, and downregulated sarco(endo)plasmic reticulum
      Ca(2+)-ATPase levels, the effects of which were negated by metallothionein.
      Treatment with tunicamycin caused cardiomyocyte mitochondrial injury, as
      evidenced by decreased mitochondrial membrane potential (??m, assessed by JC-1
      staining), the effect of which was negated by the antioxidant. Moreover,
      tunicamycin challenge dramatically facilitated myocardial apoptosis as manifested
      by increased Bax, caspase 9, and caspase 12 protein levels, as well as elevated
      caspase 3 activity. Interestingly, metallothionein transgene significantly
      alleviated tunicamycin-induced myocardial apoptosis. CONCLUSION: Taken together,
      our data favor a beneficial effect of metallothionein against ER stress-induced
      cardiac dysfunction possibly associated with attenuation of myocardial apoptosis.

PMID- 25968956
TI  - Attempted Suicide, Self-Harm, and Psychological Disorder Among Young Offenders in
      Custody.
AB  - This study aims to identify risk factors for suicide and self-harm among young
      offenders. The data are from the 2009 New South Wales Young People in Custody
      Health Survey. The sample (N = 313) were 88% male and 48% Aboriginal. Sixteen
      percent reported ever having suicidal thoughts and 10% reported a suicide
      attempt. Twenty-one percent reported thoughts of self-harm and 16% reported
      actual self-harm. Female young offenders reported higher rates of suicidal
      behavior and self-harm compared to males. Significant correlates of attempted
      suicide and self-harm included childhood adversity and psychiatric disorder. This
      study finds that young offenders are at high risk of suicidal and self-harm
      behaviors. Early identification and support among this vulnerable group are
      critical. 

PMID- 25968955
TI  - Differences in risk factors for the onset of albuminuria and decrease in
      glomerular filtration rate in people with Type 2 diabetes mellitus: implications
      for the pathogenesis of diabetic kidney disease.
AB  - AIMS: To determine differences in predictors of albuminuria and decreased
      estimated GFR in Japanese people with Type 2 diabetes mellitus without chronic
      kidney disease. METHODS: This single-centre observational cohort study involved
      1802 Japanese people with Type 2 diabetes with normoalbuminuria and estimated GFR
      >= 60 ml/min/1.73 m(2) (740 women; mean +/- sd age 58 +/- 12 years). Two separate
      outcomes were evaluated: onset of albuminuria ( >= 30 mg/g creatinine,
      albuminuria cohort; n = 1655) and decrease in estimated GFR ( < 60 ml/min/1.73
      m(2) ; estimated GFR cohort; n = 1777). A Cox proportional hazards model was used
      to identify significant predictors for each outcome. RESULTS: During a median
      follow-up period of 6.9 years for the albuminuria cohort and 8.0 years for the
      estimated GFR cohort, 181 and 316 individuals reached the respective outcome. The
      5-year cumulative incidence of albuminuria was 8.3%, and that of decreased
      estimated GFR was 10.4%. In the multivariate Cox model, greater urinary albumin
      to-creatinine ratio, presence of diabetic retinopathy and higher HbA1c levels
      were associated with both outcomes. Unique risk factors for onset of albuminuria
      were male gender and higher uric acid levels; those for decreased estimated GFR
      were older age, greater systolic blood pressure, and lower baseline estimated GFR
      and HDL cholesterol levels. CONCLUSIONS: Identification of both common and
      distinct predictive factors for onset of albuminuria and decreased estimated GFR
      support the hypothesis that both common and distinct pathophysiological
      mechanisms are involved in the development of these two manifestations of chronic
      kidney disease in diabetes.

PMID- 25968957
TI  - Periodontitis and Rheumatoid Arthritis: What Do We Know?
AB  - BACKGROUND: Currently, in the field of rheumatology, there is much attention
      given towards the possible causality between periodontitis and rheumatoid
      arthritis (RA), specifically regarding the role of Porphyromonas gingivalis (Pg).
      This bacterium is unique, having a citrullinating enzyme. Antibodies against
      citrullinated proteins are rather specific for RA. METHODS: Because causality is
      ultimately tested in longitudinal cohort studies which currently do not exist for
      periodontitis and RA, this commentary applied Bradford Hill criteria on the
      existing literature to assess causality as the most likely interpretation of this
      association. CONCLUSIONS: From an epidemiologic point of view, patients with RA
      have a higher incidence of periodontal disease than individuals without RA. In
      addition, there is a dose-response pattern in the association between the
      severity of periodontitis and RA disease activity. There are indications that
      periodontitis precedes RA, but there is no evidence yet available to show that Pg
      plays a direct role in this temporal relationship. The role of the unique
      characteristic of citrullination by Pg remains unexplained. However, in animal
      models, citrullination by Pg plays a distinct role in the development and
      aggravation of experimental arthritis. Although the role of Pg in RA remains
      speculative, a causative role for periodontitis as a chronic inflammatory disease
      caused by infectious agents in RA seems biologically plausible.

PMID- 25968958
TI  - The Association Between Thalassemia Major and Periodontal Health.
AB  - BACKGROUND: The aim of this cross-sectional study is to compare the local and
      systemic levels of soluble receptor activator of nuclear factor-kappaB ligand
      (sRANKL), osteoprotegerin (OPG), a proliferation-inducing ligand (APRIL), B-cell
      activating factor (BAFF), interleukin (IL)-6, and IL-8 in biofluids of patients
      with thalassemia major (TM) with or without gingivitis. METHODS: Seventy-seven
      patients are included in this study (TM, n = 29; systemically healthy, n = 48).
      Gingival crevicular fluid (GCF), saliva, and serum levels of IL-6, IL-8, sRANKL,
      OPG, BAFF, and APRIL were determined by enzyme-linked immunosorbent assay. Data
      were analyzed by appropriate non-parametric or parametric statistical tests.
      RESULTS: Median GCF, serum, and saliva levels for BAFF (P <0.001) and IL-6 and IL
      8 (P <0.005) were higher in TM gingivitis than in systemically healthy gingivitis
      (P <0.001). GCF, serum, and saliva levels for APRIL, sRANKL, IL-6, and IL-8 were
      higher in TM than in systemically and periodontally healthy comparison groups (P
      <0.05). Positive correlations were found between bleeding on probing (BOP),
      plaque index (PI) scores, and GCF APRIL, serum sRANKL, serum OPG, and sRANKL
      concentrations in TM groups (P <0.05). Several significant positive correlations
      were found between BOP, PI scores, and biofluid parameters also in systemically
      healthy groups. CONCLUSION: TM may have a role in the underlying systemic
      hematologic condition and potentially affect gingival inflammation via
      dysregulation of lymphocytes and increased activation of osteoclasts.

PMID- 25968959
TI  - The fluorescence and infrared absorption probe para-cyanophenylalanine: Effect of
      labeling on the behavior of different membrane-interacting peptides.
AB  - Total syntheses and complete characterizations of singly substituted PheCN -based
      analogs of alamethicin AlaP, which is active on model and natural membranes, and
      the TM peptide, which inserts in a transmembrane orientation in lipid bilayers,
      are reported. The syntheses of the AlaP analogs were performed in solution, while
      those of TM and its analogs were carried out by solid phase. Using the
      cyanophenyl fluorescence and infrared (IR) absorption probe, an in-depth
      investigation of the self-association, membrane-interacting, permeabilizing, and
      orientation properties of these peptides were conducted. The aromatic residue
      incorporated induces only a negligible modification to the properties of the
      parent peptides. The PheCN IR absorption band was located between 2228 and 2230
      cm(-1) for all peptides, irrespective of the position of labeling. By contrast,
      as the width of this band varied significantly with the depth of probe insertion
      in the bilayer, it could represent a good marker of the PheCN position in
      phospholipid membranes.

PMID- 25968960
TI  - 2014 EASO Position Statement on the Use of Anti-Obesity Drugs.

PMID- 25968961
TI  - Relaxed Observance of Traditional Marriage Rules Allows Social Connectivity
      without Loss of Genetic Diversity.
AB  - Marriage rules, the community prescriptions that dictate who an individual can or
      cannot marry, are extremely diverse and universally present in traditional
      societies. A major focus of research in the early decades of modern anthropology,
      marriage rules impose social and economic forces that help structure societies
      and forge connections between them. However, in those early anthropological
      studies, the biological benefits or disadvantages of marriage rules could not be
      determined. We revisit this question by applying a novel simulation framework and
      genome-wide data to explore the effects of Asymmetric Prescriptive Alliance, an
      elaborate set of marriage rules that has been a focus of research for many
      anthropologists. Simulations show that strict adherence to these marriage rules
      reduces genetic diversity on the autosomes, X chromosome and mitochondrial DNA,
      but relaxed compliance produces genetic diversity similar to random mating.
      Genome-wide data from the Indonesian community of Rindi, one of the early study
      populations for Asymmetric Prescriptive Alliance, are more consistent with
      relaxed compliance than strict adherence. We therefore suggest that, in practice,
      marriage rules are treated with sufficient flexibility to allow social
      connectivity without significant degradation of biological diversity. 

PMID- 25968962
TI  - Olfaction and Aging: A Mini-Review.
AB  - Decreased olfactory function is very common in the older population, being
      present in >50% of individuals aged between 65 and 80 years and in 62-80% of
      those >80 years of age. Smell dysfunction significantly influences physical well
      being, quality of life, nutritional status as well as everyday safety and is
      associated with increased mortality. Multiple factors contribute to age-related
      olfactory sensory loss, including nasal engorgement, cumulative damage of the
      olfactory epithelium from environmental insults, a reduction in mucosal
      metabolizing enzymes, sensory loss of receptor cells to odorants, and changes in
      neurotransmitter and neuromodulator systems. In addition, structural and
      functional abnormalities of the olfactory epithelium, olfactory bulb, central
      olfactory cortex, and basic olfactory circuitry, which are related to the
      neuronal expression of aberrant proteins in these areas, may result in olfactory
      sensory impairment in aging and neurodegenerative diseases. Impaired odour
      identification is associated with a decrease in cognitive abilities and memory
      decline. A reduction in the sense of smell is considered to potentially represent
      an early and important warning of neurodegenerative disorders, particularly of
      Parkinson's disease and Alzheimer's disease, and, in mild cognitive impairment,
      olfactory impairment may herald progression to dementia. Further investigations
      of the potential role of olfactory dysfunction in the early diagnosis and
      treatment of neurodegenerative diseases are warranted. 

PMID- 25968963
TI  - Trigeminal Neuralgia Caused by Venous Angioma: A Case Report and Review of the
      Literature.
AB  - BACKGROUND: Trigeminal neuralgia typically occurs in the middle-aged to elderly
      population, is believed to be related to abnormal conduction within the
      trigeminal nerve, and is possibly is attributable to changes in myelin induced by
      pulsatile mechanical trauma from an adjacent vessel. At the point just before it
      enters the brainstem, there is a short segment at which nerve axons are still
      ensheathed in central myelin (produced by oligodendrocytes), but after a few
      millimeters, there is a transition to peripheral myelin (produced by Schwann
      cells). The region of this transition is called the Obersteiner-Redlich zone. It
      is thought that the area of the nerve containing the central form of myelin is
      especially susceptible to pathologic changes from vascular contact that result in
      demyelination and altered conduction. When associated with a venous angioma at
      the root entry zone, trigeminal neuralgia usually presents at a younger age.
      METHODS: We report a 34-year-old man with a complaint of left hemifacial stabbing
      pain in maxillomandibular area that was triggered by chewing and speaking. On
      examination, no neurologic deficit was detected. The pain was not relieved
      significantly, even with the administration of carbamazepine. Magnetic resonance
      imaging demonstrated venous angioma in the left cerebello-pontine region.
      RESULTS: Microvascular decompression was performed uneventfully. The patient's
      pain was completely relieved without neurologic deficits. CONCLUSION: It seems
      that the trigeminal neuralgia caused by venous angioma may occur in the younger
      population. In most cases, the vessel that caused compression can be identified
      with magnetic resonance imaging without the need for intensive conventional
      angiography.

PMID- 25968964
TI  - Clinical Relevance of Racial Differences in Cerebrovascular Diseases.

PMID- 25968965
TI  - Endoscopic Treatment of Temporal Arachnoid Cysts in 34 Patients.
AB  - INTRODUCTION: Arachnoid cysts are lesions present in 1% of the population and
      usually found in the temporal fossa. Clinical and radiologic presentations can
      differ greatly. Despite intensive research, it is still debatable which patients
      will benefit from surgery. OBJECTIVE: This study aims to investigate the
      pretreatment parameters influencing the outcome after neuroendoscopic treatment
      of temporal arachnoid cysts. MATERIALS AND METHODS: A retrospective analysis of
      34 patients who underwent an endoscopic fenestration of a temporal arachnoid cyst
      between July 1991 and December 2013 was performed. RESULTS: In symptomatic
      patients, there was a clinical improvement in 76.4% of cases. The best results
      were found in treating symptoms related to intracranial hypertension, acute
      neurologic defects, and macrocrania. Patients with temporal lobe epilepsy
      improved after cyst fenestration in 33.3% of cases. Behavioral problems and
      psychomotor retardation remained largely unchanged. Patients with a complex
      neurologic presentation, often from a congenital syndrome and combined with an
      intellectual disability, had the least benefit from endoscopic surgery.
      Radiologic follow-up showed a cyst volume decrease in 91.2% of cases.
      Complications were present in 29.4%, but were mostly minor and transient.
      CONCLUSION: This study demonstrates that patients with symptoms related to
      intracranial hypertension, acute neurologic deficits, and macrocrania have the
      best postoperative outcome. Also, patients with ipsilateral temporal lobe
      epilepsy seem to be good candidates for endoscopic arachnoid cyst fenestrations.
      In complex neurologic disorders without one of the previously mentioned symptoms,
      endoscopy remains less successful.

PMID- 25968966
TI  - Single-day sodium picosulfate and magnesium citrate versus split-dose
      polyethylene glycol for bowel cleansing prior to colonoscopy: A prospective
      randomized endoscopist-blinded trial.
AB  - BACKGROUND AND AIM: The intake of polyethylene glycol (PEG) prior colonoscopy is
      frequently associated with nausea and abdominal discomfort. The aim of this study
      was to investigate whether sodium picosulfate and magnesium citrate (PMC) is
      superior to a polyethylene glycol (PEG) preparation in regard to patient
      acceptance. Furthermore, it investigates possible differences in efficiency and
      patient safety. METHODS: In a randomised, prospective, and endoscopist-blinded
      study patients were 1:1 randomized to either use PMC or 4-L PEG in order to
      prepare for colonoscopy. Cleansing regimes consisted of a split-dose
      administration in the PEG arm and standard administration in the PMC arm. Primary
      end point was proportion of patients evaluating the bowel preparation procedure
      as "very distressing," defined as >= 8 points on a 10-point numeric rating scale
      (NRS). Secondary end points were quality of bowel preparation and electrolyte
      parameters. RESULTS: PMC bowel-cleansing procedure was better tolerated compared
      with PEG (PMC(NRS<8)  = 89.9% vs PEG(NRS<8)  = 79.2%, P = 0.037). Mean declines
      in serum sodium (DeltaSodium(PEG)  = -0.76 +/- 3.07 vs DeltaSodium(PMC)  = -3.38
      +/- 3.56 mmol/L; P < 0.001), chloride (DeltaChloride(PEG)  = -1.00 +/- 3.22 vs
      DeltaChloride(PMC)  = -3.49 +/- 3.51 mmol/L; P < 0.001), and osmolality
      (DeltaOsmolality(PEG)  = -4.23 +/- 6.82 vs DeltaOsmolality(PMC)  = -8.83 +/- 7.43
      mosmol/kg; P < 0.001) were higher in the PMC arm than in the PEG arm.
      Hyponatremia after bowel preparation occurred more often in PMC (21.2%) than in
      PEG (4.0%) (P < 0.001). Successful preparation was achieved more frequently in
      the PEG arm (42.9% vs 82.2%; P < 0.001). CONCLUSION: Standard
      picosulfate/magnesium citrate is better accepted than a split-dose PEG regimen.
      From the perspective of successful preparation and patients' safety, PEG is
      superior to PMC.

PMID- 25968967
TI  - Remote ischemic preconditioning does not increase circulating or effector organ
      concentrations of proopiomelanocortin derivates.
AB  - OBJECTIVES: The aim of the present study was to compare changes in circulating
      levels of proopiomelanocortin (POMC) derivates and lactate after remote ischemic
      preconditioning (IPC) and physical exercise. INTRODUCTION: Remote IPC (rIPC) is
      cardioprotective following acute myocardial infarction and major cardiac surgery.
      A blood-borne, transferable factor, released following not only rIPC but also
      vigorous exercise, mediates protection that is abolished by naloxone suggesting
      involvement of an opioid-receptor-dependent pathway. DESIGN: Eight healthy
      volunteers underwent rIPC by four cycles of 5-min inflation of a pneumatic
      tourniquet to 200 mmHg interrupted by 5 min of deflation. Subsequently,
      circulating plasma levels of POMC derivates, cortisol, and lactate were measured.
      After 3 days, the volunteers completed a vigorous exercise program, after which
      the same compounds were measured. RESULTS: While rIPC was not associated with any
      significant increase in circulating POMC derivates or lactate, exercise induced
      significant elevation of both compared with baseline. CONCLUSIONS: We were not
      able to demonstrate a detectable increase in circulating POMC derivates by a
      standard rIPC stimulus, suggesting that rIPC effect is not mediated by local or
      detectable central release of these derivates.

PMID- 25968968
TI  - Patient-centred home-based management of heart failure. Findings from a
      randomised clinical trial evaluating a tablet computer for self-care, quality of
      life and effects on knowledge.
AB  - OBJECTIVES: To evaluate whether a new home intervention system (HIS,
      OPTILOGG((r))) consisting of a specialised software, a tablet computer (tablet)
      wirelessly connected to a weight scale may improve self-care behaviour, health
      related quality of life (HRQoL), knowledge about heart failure (HF) and reduce
      hospital days due to HF. DESIGN: 82 patients (32% females) with mean age: 75 +/-
      8 years hospitalised with HF were randomised at discharge to an intervention
      group (IG) equipped with the HIS or to a control group (CG) receiving standard HF
      information only. The tablet contained information about HF and lifestyle advice
      according to current guidelines. It also showed present dose of diuretic, changes
      in patient-measured weight and HRQoL over time. RESULTS: After 3 months the IG
      displayed a dramatic improvement in self-care with p < 0.05 (median IG: 17 [IQR:
      13, 22] and CG: 21 [IQR: 17, 25]). The disease-specific HRQoL was measured by
      Kansas City Cardiomyopathy Questionnaire. The IG had significantly higher score
      (median IG: 65.1 [IQR: 38.5, 83.3] vs. CG: 52.1 [IQR: 41.1, 64.1] p < 0.05) and
      an improved physical limitation (median IG: 54.2 [IQR: 37.7, 83.3] vs. CG: 45.8
      [IQR: 25.0, 54.2] p < 0.05) There was no difference in knowledge. IG showed fewer
      HF-related days in the hospital, with 1.3 HF-related hospital days/patient versus
      3.5 in CG (risk ratio: 0.38; 95% confidence interval: 0.31-0.46; p < 0.05).
      CONCLUSION: HF patients with a HIS tablet computer and scale improved in self
      care and HRQoL. Days in hospital due to HF were reduced. A medical device that is
      easy to use can be a valuable tool for improving self-care and outcome in
      patients with HF.

PMID- 25968969
TI  - Age-related decline in mitral peak diastolic velocities is unaffected in well
      trained runners.
AB  - OBJECTIVES: We examined whether diastolic left ventricular function in young and
      senior lifelong endurance runners was significantly different from that in
      sedentary age-matched controls, and whether lifelong endurance running appears to
      modify the age-related decline in diastolic left ventricular function. DESIGN:
      The study comprised 17 senior athletes (age: 59-75 years, running distance: 30-70
      km/week), 10 young athletes (age: 20-36 years, matched for running distance), and
      11 senior and 12 young weight-matched sedentary controls. Peak early (E) and late
      (A) mitral inflow and early (e') and late (a') diastolic and systolic (s')
      annular longitudinal tissue Doppler velocities were measured by echocardiography
      during four stages (rest, supine bike exercise at 30% and 60% of maximal
      workload, and recovery). RESULTS: The athletes had marked cardiac remodeling,
      while overall differences in mitral inflow and annular tissue Doppler velocities
      during rest and exercise were more associated with age than with training status.
      The senior participants had lower E/A at rest, overall lower E, e' and s', and
      greater E/e' compared to the young participants (all values of P < 0.05). The
      athletes had greater E/A (P = 0.004), but tissue Doppler velocities were not
      different from those of the controls. CONCLUSIONS: Lifelong endurance running was
      not found to be associated with major attenuation of the age-related decline in
      diastolic function at rest or during exercise.

PMID- 25968970
TI  - Blood pressure morning surge, exercise blood pressure response and autonomic
      nervous system.
AB  - OBJECTIVE: We investigated blood pressure (BP) response to exercise with respect
      to BP morning surge (MS), and the association between MS, exercise treadmill test
      (ETT) and heart rate variability (HRV) indices. DESIGN: Eighty-four healthy
      subjects without hypertension were enrolled. Ambulatory BP monitoring and 24-hour
      Holter recordings were obtained for sleep-trough MS and HRV indices: low
      frequency (LF) component, high-frequency (HF) component and LF/HF ratio. ETT was
      performed, and BPs were obtained at rest, end of each stage, and recovery. Third
      minute heart rate recovery (HRR) and BP recovery ratio (BPRR) were calculated.
      RESULTS: When analysed in quartiles of MS, systolic BP at low workloads was
      higher in the highest than in the lowest quartile, although maximum BPs at
      maximum exercise were not significantly different. BPRR was highest in the
      highest quartile in contrast to HRR, which was lowest in the highest quartile.
      LF/HF was highest during both at daytime and night-time in the highest quartile.
      BPRR and LF/HF were positively, and HRR was inversely associated with MS.
      CONCLUSIONS: Subjects with a high MS have higher BP at low workloads, at which
      most daily activities are performed, and impairment in some indices, which
      indirectly reflect the autonomic nervous system.

PMID- 25968971
TI  - Comparison of renal outcomes in off-pump versus on-pump coronary artery bypass
      grafting: A systematic review and meta-analysis of randomized controlled trials.
AB  - AIM: The objective of this meta-analysis was to compare the effects of off-pump
      and on-pump coronary artery bypass grafting (CABG) on acute kidney injury (AKI)
      and the need of dialysis after surgery. METHODS: Comprehensive literature
      searches for randomized controlled trials (RCTs) of CABG with on-pump and off
      pump was performed using MEDLINE, EMBASE, Cochrane Database of Systematic
      Reviews, Cochrane Central Register of Controlled Trials Systematic Reviews and
      clinicaltrials.gov from inception through September 2014. Primary outcomes were
      the incidence of AKI and the need of dialysis. Mortality was assessed among the
      studies that reported renal outcomes. Pooled risk ratios (RRs) and 95% confidence
      interval (CI) were calculated using a random-effect, generic inverse variance
      method. RESULTS: Thirty-three RCTs with 17 322 patients were enrolled in our
      study. Patients in the off-pump CABG group had overall lower incidence of AKI
      (19.1%) compared with the on-pump CABG group (22.2%). There was a protective
      effect of off-pump CABG on the incidence of AKI compared with the on-pump CABG
      group (RR: 0.87; 95% CI: 0.77-0.98). However, there was no significant difference
      in the need for dialysis in the off-pump group compared with the on-pump group
      (RR: 0.84; 95% CI 0.63-1.13). Within the selected trials, post hoc analysis
      assessing the mortality outcome demonstrated a pooled RR of 0.97 (95% CI, 0.77
      1.23) in off-pump versus on-pump CABGs. CONCLUSIONS: Our study demonstrates a
      beneficial effect of off-pump CABG on the incidence of AKI. However, our meta
      analysis does not show benefits of the need of dialysis or survival among
      patients undergoing off-pump CABG.

PMID- 25968972
TI  - A diagnosis based on the electrocardiogram before laboratory results were
      available.

PMID- 25968973
TI  - A diagnosis based on the electrocardiogram before laboratory results were
      available.

PMID- 25968975
TI  - 14,15-epoxyeicosatrienoic Acid suppresses cigarette smoke extract-induced
      apoptosis in lung epithelial cells by inhibiting endoplasmic reticulum stress.
AB  - BACKGROUND/AIMS: Epoxyeicosatrienoic acids (EETs), a type of lipid mediators
      produced by cytochrome P450 epoxygenases, exert anti-inflammatory, angiogenic,
      anti-oxidative and anti-apoptotic effects. However, the role of EETs in cigarette
      smoke-induced lung injury and the underlying mechanisms are not fully known. The
      aim of this study was to explore the effects of CYP2J2-EETs on cigarette smoke
      extracts (CSE)-induced apoptosis in human bronchial epithelial cell line (Beas
      2B) and the possible mechanisms involved. METHODS: Cytochrome P450 epoxygenase
      2J2 (CYP2J2) and its metabolites EETs were assessed by western blotting or LC-MS
      MS. Cell viability and apoptosis were determined by MTT assay and AnnexinV-PI
      staining. Reactive oxygen species (ROS) were assessed by measuring H2DCFDA.
      Caspase-3, HO-1, MAPK and endoplasmic reticulum (ER) stress-related markers
      GRP78, p-elF2a, and CHOP were evaluated by western blotting. RESULTS: CSE
      suppressed expression of both CYP2J2 and EET by Beas-2B cells. CSE also induced
      apoptosis, the generation of ROS and the ER stress in Beas-2B cells. These
      changes were abolished by pretreatment with exogenous 14,15-EET while
      pretreatment with 14,15-EEZE, a selective EET antagonist, abolished the
      protective effects of 14,15-EET. In addition, EETs increased the expression of
      antioxidant enzyme HO-1. Furthermore, 14,15-EET reduced CSE-induced activation of
      p38 and JNK. CONCLUSION: The data suggest that CYP2J2-derived EETs protect
      against CSE-induced lung injury possibly through attenuating ER stress.

PMID- 25968976
TI  - Electrifying the disk: a modular rotating platform for wireless power and data
      transmission for Lab on a disk application.
AB  - We present a design for wireless power transfer, via inductively coupled coils,
      to a spinning disk. The rectified and stabilised power feeds an Arduino
      compatible microcontroller (MUC) on the disc, which in turn drives and monitors
      various sensors and actuators. The platform, which has been conceived to flexibly
      prototype such systems, demonstrates the feasibility of a wireless power supply
      and the use of a MUC circuit, for example for Lab-on-a-disk applications, thereby
      eliminating the need for cumbersome slip rings or batteries, and adding a cogent
      and new degree of freedom to the setup. The large number of sensors and actuators
      included demonstrate that a wide range of physical parameters can be easily
      monitored and altered. All devices are connected to the MUC via an I(2)C bus,
      therefore can be easily exchanged or augmented by other devices in order to
      perform a specific task on the disk. The wireless power supply takes up little
      additional physical space and should work in conjunction with most existing Lab
      on-a-disk platforms as a straightforward add-on, since it does not require
      modification of the rotation axis and can be readily adapted to specific
      geometrical requirements. 

PMID- 25968974
TI  - Improved immunogenicity and protective efficacy of a divalent DNA vaccine
      encoding Brucella L7/L12-truncated Omp31 fusion protein by a DNA priming and
      protein boosting regimen.
AB  - Brucellosis is one of the most common zoonotic diseases caused by species of
      Brucella. At present, there is no commercially available vaccine for the human
      brucellosis. Brucella melitensis and Brucella abortus are the main causes of
      human brucellosis, worldwide. The outer membrane protein 31 (Omp31) and L7/L12
      are immunodominant and protective antigens conserved among human Brucella
      pathogens. The purpose of the current study was to evaluate and compare the
      immunogenicity and protective efficacy of the L7/L12-TOmp31 construct
      administered as DNA/DNA and DNA/Pro vaccine regimens. Vaccination of BALB/c mice
      with the DNA/Pro regimen provided more protection levels against B. melitenisis
      and B. abortus challenge than did the DNA/DNA regimen. IgG1 and IgG2a titers were
      higher in the sera from DNA/Pro-immunized mice than in those from mice immunized
      with DNA alone. Moreover, splenocytes from DNA/Pro-immunized mice produced
      significantly higher levels of IFN-gamma than did those from mice given DNA
      alone. The pcDNA-L7/L12-TOmp31 priming followed by rL7/L12-TOmp31 boosting led to
      improved protection against B. abortus or B. melitensis infection.

PMID- 25968977
TI  - The Effect of Cigarette Smoke on the Translocator Protein (TSPO) in Cultured Lung
      Cancer Cells.
AB  - Lung cancer is prevalent in cigarette smokers. The mitochondrial membrane
      translocator protein (TSPO), is thought to protect cells from free radical
      damage. We examined the effect of cigarette smoke (CS) (containing free radicals)
      alone and in the presence of saliva (containing redox active free iron), on
      survival of H1299 lung cancer cells and on their mitochondrial characteristics,
      and whether TSPO binding was influenced by CS and by saliva. We exposed H1299
      cells to CS in the presence/absence of saliva and also characterized TSPO binding
      in the cells using [3H]PK 11195 as a radioligand. CS induced a significant drop
      in mitochondrial potential (DeltaPsim), while addition of saliva did not lead to
      further loss of DeltaPsim (42.5% vs. 39.85%). Scatchard analysis of the
      saturation curve of [3H]PK 11195 binding (0.2-6 nM final concentration) yielded a
      straight-line plot (R =  0.9). Average Bmax value was 3274 +/- 787 fmol/mg of
      protein, and average Kd value was 9.2 +/- 1.3 nM. Benzodiazepine diazepam
      partially prevented decrease in cell survival following exposure to CS and redox
      active iron containing media (saliva) while benzodiazepine clonazepam did not,
      indicating that this effect is TSPO-specific. Exposure of cells to CS resulted in
      alternation of biomolecules expressed by CLs peroxidation, reduction of TSPO
      binding, and depletion of the mitochondrial potential. This irreversible damage
      was enhanced in the presence of saliva. All these modulations may result in
      cellular death increase following CS exposure, enhanced in the presence of
      saliva.

PMID- 25968978
TI  - Sepsis guidelines: Clinical practice implications.
AB  - The Surviving Sepsis Campaign 2012 Guidelines offer recommendations for the care
      of severely septic patients. These guidelines are appraised and summarized
      briefly in this article, and a case example illustrates the integration process.
      These guidelines are important for multidisciplinary team members working
      together toward the common goal of reducing sepsis mortality. 

PMID- 25968979
TI  - 2015: The year of the APRN Consensus Model.

PMID- 25968980
TI  - Nurse practitioners: Enhancing healthcare for 50 years.

PMID- 25968982
TI  - Safe and effective NSAID use.

PMID- 25968985
TI  - Using specialized standardized patients to improve differential diagnoses.
AB  - A Specialized Standardized Patient (SSP) is a standardized patient who has
      advanced nursing education. This article describes an experience of introducing
      advanced practice registered nurses as SSPs into an advanced health assessment
      course. The article also discusses the simulated clinical experience and the
      desired course outcome that the student will be able to merge the patient history
      and physical exam findings to develop differential diagnoses. 

PMID- 25968987
TI  - Comparison of HOMA-IR, HOMA-beta% and disposition index between US white men and
      Japanese men in Japan in the ERA JUMP study: was the calculation of disposition
      index legitimate?

PMID- 25968988
TI  - Comparative genomics: beyond the horizon of the next research grant.
AB  - With the development of agriculture and food processing techniques, humanity has
      recently challenged the rules of a billion-year-old experiment called evolution.
      In this experiment the availability of food in a particular niche has been one of
      the major driving forces to shape particular species. Comparative genomics is a
      new research discipline that investigates two or more genomes from different
      species in order to find specific genetic adaptations that explain a 'workable
      match' between genetic make-up and environmental constraints such as nutrition.
      Three recent examples in the literature illustrate how selection of particular
      genes can contribute to species-specific adaptations that allow them to
      recognise, secure and digest particular types of food and metabolise its
      ingredients. There is growing consensus that the recent changes in human diet and
      physical activity play an active role in the rapid growth of the prevalence of
      obesity and diabetes. The working hypothesis of the present article is that in
      the future a more advanced level of comparative genomics of the many natural
      workable matches of natural species will lead to a much better understanding of
      the dynamics and regulation of integrated metabolism. It is anticipated that this
      deeper understanding will lead to novel insights into the mechanism of human
      diabetes and new strategies for diabetes prevention and treatment. This is one of
      a series of commentaries under the banner '50 years forward', giving personal
      opinions on future perspectives in diabetes, to celebrate the 50th anniversary of
      Diabetologia (1965-2015).

PMID- 25968990
TI  - The Total Calvarial Remodeling with Transsutural Distraction Osteogenesis of 21
      Cases of Craniosynostosis: New, Efficient, Safe and Natural Method in
      Craniosynostosis Surgery.
AB  - INTRODUCTION: The majority of the present distraction osteogenesis techniques
      involve local site expansion that only produces localized decompression and
      affords limited decompression and cosmetic results. We designed a new surgical
      procedure, total calvarial transsutural distraction osteogenesis (TSuDO).
      METHODS: We performed total calvarial TSuDO surgical procedures in 21 children.
      The total calvarial TSuDO method consisted of suturectomy and distraction for the
      sagittal, bicoronal and bilambdoid sutures. RESULTS: The mean surgery duration
      was 110 +/- 16 min, the mean transfusion volume was 38 +/- 45 ml, an average 4.1
      +/- 0.4 distractors were applied with a mean latency period of 3.3 +/- 0.9 days.
      The mean activation period was 45 +/- 18 days with a consolidation period of 54
      +/- 23 days. There were 3 complication cases of early removal of the distractors:
      1 boy with transient 6th cranial nerve palsy accompanied by fever and 2 children
      with mild pus discharge from the distractor sites. Preoperative lumbar puncture
      pressures decreased significantly after distractor removal secondary to surgery
      (p < 0.001). The preoperative cranium size increased significantly (p < 0.001).
      CONCLUSION: Total calvarial TSuDO is a simple and safe procedure that may produce
      wide generalized decompression and good cranial configurations that most closely
      resemble normal skulls.

PMID- 25968989
TI  - Age-Related Changes in MicroRNA Expression and Pharmacogenes in Human Liver.
AB  - Developmental changes in the liver can significantly impact drug disposition. Due
      to the emergence of microRNAs (miRNAs) as important regulators of drug
      disposition gene expression, we studied age-dependent changes in miRNA
      expression. Expression of 533 miRNAs was measured in 90 human liver tissues
      (fetal, pediatric [1-17 years], and adult [28-80 years]; n = 30 each). In all,
      114 miRNAs were upregulated and 72 were downregulated from fetal to pediatric,
      and 2 and 3, respectively, from pediatric to adult. Among the developmentally
      changing miRNAs, 99 miRNA-mRNA interactions were predicted or experimentally
      validated (e.g., hsa-miR-125b-5p-CYP1A1; hsa-miR-34a-5p-HNF4A). In human liver
      samples (n = 10 each), analyzed by RNA-sequencing, significant negative
      correlations were observed between the expression of >1,000 miRNAs and mRNAs of
      drug disposition and regulatory genes. Our data suggest a mechanism for the
      marked changes in hepatic gene expression between the fetal and pediatric
      developmental periods, and support a role for these age-dependent miRNAs in
      regulating drug disposition. 

PMID- 25968991
TI  - Serum Triglyceride Levels and Cardiovascular Disease Events in Koreans.
AB  - OBJECTIVES: Hypercholesterolemia, especially elevated levels of LDL-cholesterol,
      is a well-known risk factor for cardiovascular disease (CVD). However, the role
      of triglycerides in CVD risk remains controversial. METHODS: We enrolled 86,476
      individuals who had undergone a general health checkup at Asan Medical Center
      between January 2007 and June 2011. After exclusion criteria were applied to the
      total cohort, 76,434 participants were included. CVD events and death were
      gathered from the nationwide health insurance claims database and death
      certificates using ICD-10 codes. RESULTS: Age- and sex-adjusted odds ratios (ORs)
      of the higher triglyceride group were significantly increased: 1.52 (95% CI: 1.27
      1.82) for major CVD events, 1.53 (95% CI: 1.24-1.88) for major ischemic heart
      disease events, and 1.49 (95% CI: 1.37-1.63) for overall CVD events. After
      adjustment for multiple risk factors including HDL-cholesterol, ORs for overall
      CVD events were significantly increased in the higher triglyceride group. When
      the analysis was stratified according to BMI, hypertension, and glycemic status
      at baseline, age- and sex-adjusted ORs for the outcomes were significantly
      increased in the higher triglyceride group with nonobese, normotensive, or
      nondiabetic subjects. CONCLUSIONS: Hypertriglyceridemia is independently
      associated with an increased risk for CVD, especially in nonobese, normotensive,
      or nondiabetic individuals.

PMID- 25968993
TI  - Measurement of the modulation transfer function of an X-ray microscope based on
      multiple Fourier orders analysis of a Siemens star.
AB  - Soft X-ray tomography (SXT) is becoming a powerful imaging technique to analyze
      eukaryotic whole cells close to their native state. Central to the analysis of
      the quality of SXT 3D reconstruction is the estimation of the spatial resolution
      and Depth of Field of the X-ray microscope. In turn, the characterization of the
      Modulation Transfer Function (MTF) of the optical system is key to calculate both
      parameters. Consequently, in this work we introduce a fully automated technique
      to accurately estimate the transfer function of such an optical system. Our
      proposal is based on the preprocessing of the experimental images to obtain an
      estimate of the input pattern, followed by the analysis in Fourier space of
      multiple orders of a Siemens Star test sample, extending in this way its measured
      frequency range. 

PMID- 25968994
TI  - Accurate measurement of the residual birefringence in VECSEL: Towards
      understanding of the polarization behavior under spin-polarized pumping.
AB  - In this paper we report birefringence measurements of an optically pumped (100)
      oriented InGaAs/GaAsP multiple quantum well (MQWs) Vertical External Cavity
      Surface Emitting Laser (VECSEL) in oscillating conditions. The proposed technique
      relies on the measurement in the microwave domain of the beatnote between the
      oscillating mode and the amplified spontaneous emission of the cross-polarized
      non-lasing field lying in the following longitudinal mode. This technique is
      shown to offer extremely high sensitivity and accuracy enabling to track the
      amount of residual birefringence according to the laser operation conditions. The
      experience fits within the broader framework of polarization selection in spin
      injected lasers. 

PMID- 25968992
TI  - Epidemiological updates and economic losses due to Taenia hydatigena in sheep
      from Sardinia, Italy.
AB  - The aim of this study was to investigate the epidemiology and transmission of
      Taenia hydatigena in sheep and dogs from Sardinia and the economic estimation of
      losses due to this metacestodosis in lambs. A total of 7781 Sarda breed lambs
      were examined at abattoirs for the detection of Cysticercus tenuicollis or
      necrotic-haemorrhagic tracks of their migration. Morphological and molecular
      identification of parasites was carried out. Individual faecal samples from 300
      dogs were examined for copromicroscopic investigations and coproELISA assay. An
      overall prevalence of 14.6% for T. hydatigena cysticercosis was found in the
      examined lambs. In total, 10,807 parasitary tracks were found, with an abundance
      of 1.39 and an average intensity of 9.52. The molecular analysis of the isolates
      showed an overall pairwise nucleotide divergence for the CO1 and ND1 was of 0-3.1
      and 0-3.3%, respectively. Low intra- and interspecific variation was recorded for
      C. tenuicollis isolates used in this study which suggested the absence of
      differentiation. Microscopic examination of dog faeces showed a total prevalence
      of 31.3% for endoparasites in the examined samples (94/300). Taeniid eggs were
      found in 8.3% of the dogs. The results of the monoclonal antibody ATH4 ELISA test
      showed a prevalence of 11% (33/300) for T. hydatigena coproantigens. The total
      economic costs related to cysticercosis amounted to almost ? 330,000. The
      prevalence of C. tenuicollis in 14.6% of 30-40-day-old lambs highlights the high
      parasitic pressure by T. hydatigena in the territory of Sardinia, Italy.

PMID- 25968995
TI  - Near-ML detection for MDL-impaired few-mode fiber transmission.
AB  - Few-mode fiber transmission systems are typically impaired by mode-dependent loss
      (MDL). In an MDL-impaired link, maximum-likelihood (ML) detection yields a
      significant advantage in system performance compared to linear equalizers, such
      as zero-forcing and minimum-mean square error equalizers. However, the
      computational effort of the ML detection increases exponentially with the number
      of modes and the cardinality of the constellation. We present two methods that
      allow for near-ML performance without being afflicted with the enormous
      computational complexity of ML detection: improved reduced-search ML detection
      and sphere decoding. Both algorithms are tested regarding their performance and
      computational complexity in simulations of three and six spatial modes with QPSK
      and 16QAM constellations. 

PMID- 25968996
TI  - Enhancing extraction of light from metal composite structures for plasmonic
      emitters using light-coupling effect.
AB  - This work demonstrates the efficiency and directionality of a method of
      extracting light from thin-film emissive devices by near-field evanescent waves
      in plasmonic emitters used in metal composite grating structures. A near-field
      evanescent wave can induce a surface plasmon wave on the surface of a metal under
      resonant conditions. Enhancing the near-field evanescent wave generates strong
      far-field nonlinear optical effects. This effect is highly efficient in some
      plasmonic emitter structures. Theoretical and experimental results demonstrate
      that such a metal composite grating structure exhibits good performance, a high
      coupling ratio, a small coupling angle, enhanced light extraction and a small
      FWHM. It also improves luminous efficiency, emitter angle, and directivity. 

PMID- 25968997
TI  - Inverted tetrahedron-pyramidal micropatterned polymer films for boosting light
      output power in flip-chip light-emitting diodes.
AB  - We report the improved light output power in gallium nitride-based green flip
      chip light-emitting diodes (FCLEDs) employed with inverted tetrahedron-pyramidal
      micropatterned polydimethylsiloxane (ITPM PDMS) films as an encapsulation and
      protection layer. The micropatterns are transferred into the surface of PDMS
      films from the sapphire substrate master molds with two-dimensional periodic
      hexagonal TPM arrays by a soft imprint lithography method. The ITPM PDMS film
      laminated on the sapphire dramatically enhances the diffuse transmittance (T(D))
      in a wavelength (lambda) range of 400-650 nm, exhibiting the larger T(D) value of
      ~53% at lambda = 525 nm, (cf., T(D) ~1% for planar sapphire). By introducing the
      ITPM PDMS film on the outer surface of sapphire in FCLEDs, the light output power
      is enhanced, indicating the increment percentage of ~11.1% at 500 mA of injection
      current compared to the reference FCLED without the ITPM PDMS film, together with
      better electroluminescence intensity and far-field radiation pattern.

PMID- 25968998
TI  - Deterministic single soliton generation and compression in microring resonators
      avoiding the chaotic region.
AB  - A path within the parameter space of detuning and pump power is demonstrated in
      order to obtain a single cavity soliton (CS) with certainty in SiN microring
      resonators in the anomalous dispersion regime. Once the single CS state is
      reached, it is possible to continue a path to compress it, broadening the
      corresponding single free spectral range (FSR) Kerr frequency comb. The first
      step to achieve this goal is to identify the stable regions in the parameter
      space via numerical simulations of the Lugiato-Lefever equation (LLE). Later,
      using this identification, we define a path from the stable modulation
      instability (SMI) region to the stable cavity solitons (SCS) region avoiding the
      chaotic and unstable regions. 

PMID- 25968999
TI  - Disk Yb:KGW amplifier of profiled pulses of laser driver for electron
      photoinjector.
AB  - We investigated a diode-pumped multipass disk Yb:KGW amplifier intended for
      amplifying a train of 3D ellipsoidal pulses of a laser driver for a photocathode
      of a linear electron accelerator. The multipass amplification geometry permitted
      increasing the energy of broadband (about 10 nm) pulses with a repetition rate of
      1 MHz from 0.12 uJ to 39 uJ, despite large losses (two orders of magnitude)
      introduced by a beam shaper of 3D ellipsoidal beam. The distortions of the pulse
      train envelope were minimal due to optimal delay between the moment of pump
      switching on and arrival of the first pulse of the train. 

PMID- 25969000
TI  - Systematic errors on curved microstructures caused by aberrations in confocal
      surface metrology.
AB  - Optical aberrations of microscope lenses are known as a source of systematic
      errors in confocal surface metrology, which has become one of the most popular
      methods to measure the surface topography of microstructures. We demonstrate that
      these errors are not constant over the entire field of view but also depend on
      the local slope angle of the microstructure and lead to significant deviations
      between the measured and the actual surface. It is shown by means of a full
      vectorial high NA numerical model that a change in the slope angle alters the
      shape of the intensity depth response of the microscope and leads to a shift of
      the intensity peak of up to several hundred nanometers. Comparative experimental
      data are presented which support the theoretical results. Our studies allow for
      correction of optical aberrations and, thus, increase the accuracy in
      profilometric measurements. 

PMID- 25969001
TI  - Crosstalk analysis in homogeneous multi-core two-mode fiber under bent condition.
AB  - We analyze the inter-core crosstalk in homogeneous multi-core two-mode fibers (MC
      TMFs) under bent condition by using the coupled-mode equations. In particular, we
      investigate the effects of the intra-core mode coupling on the inter-core
      crosstalk for two different types of MC-TMFs at various bending radii. The
      results show that the inter-core homo-mode crosstalk of LP(11) mode is dominant
      under the gentle fiber bending condition due to its large effective area.
      However, as the fiber bending becomes tight, the intra-core mode coupling is
      significantly enhanced and consequently makes all the inter-core crosstalk levels
      comparable to each other regardless of the mode. A similar tendency is observed
      at a reduced bending radius when the difference in the propagation constants
      between modes is large and core pitch is small.

PMID- 25969002
TI  - Observation of broadband unidirectional transmission by fusing the one-way edge
      states of gyromagnetic photonic crystals.
AB  - We experimentally demonstrate a broadband one-way transmission by merging the
      operating bands of two types of one-way edge modes that are associated with Bragg
      scattering and magnetic surface plasmon (MSP) resonance, respectively. By tuning
      the configuration of gyromagnetic photonic crystals and applied bias magnetic
      field, the fused bandwidth of unidirectional propagation is up to 2 GHz in
      microwave frequency range, much larger than either of the individual one-way
      bandwidth associated with Bragg scattering or MSP resonance. Our scheme for
      broadband one-way transmission paves the way for the practical applications of
      one-way transmission. 

PMID- 25969003
TI  - High-power continuous-wave interband cascade lasers with 10 active stages.
AB  - We report the pulsed and continuous wave (cw) performance of 10-stage interband
      cascade lasers (ICLs) emitting at both lambda ~3.2 MUm and lambda ~3.45 MUm. The
      slope efficiency is higher while the external differential quantum efficiency per
      stage remains about the same when comparison is made to earlier results for 7
      stage ICLs with similar carrier-rebalanced designs. At T = 25 degrees C, an 18
      MUm-wide ridge with 4.5 mm cavity length and high-reflection/anti-reflection
      coatings emits up to 464 mW of cw output power with beam quality factor M(2) =
      1.9, for higher brightness than has ever been reported previously for an ICL.
      When the cavity length is reduced to 1 mm, both the 10-stage and 7-stage devices
      reach 18% cw wallplug efficiency at T = 25 degrees C.

PMID- 25969004
TI  - Ultra-compact broadband mode converter and optical diode based on linear rod-type
      photonic crystal waveguide.
AB  - In this paper, we present extremely compact designs of both broadband mode
      converter and optical diode in linear rod-type photonic crystal (PhC) waveguide
      with functional region consisting of only 4 * 1 unit cells of perfect PhC. The
      dielectric distribution inside functional region are optimized by combining
      geometry projection method and method of moving asymptotes. Bidirectional mode
      converter realizes above 60% transmission efficiency within bandwidth 0.02c/a,
      where c and a represent light velocity and PhC lattice constant respectively.
      Optical diode achieves above 19 dB unidirectionality for even mode within
      bandwidth 0.01c/a. Moreover, the proposed designs have reasonable tolerance of
      rod boundary fluctuation. We expect the results will help developing recipes for
      future PhC devices in all-optical integrated circuits. 

PMID- 25969005
TI  - Finite-width plasmonic waveguides with hyperbolic multilayer cladding.
AB  - Engineering plasmonic metamaterials with anisotropic optical dispersion enables
      us to tailor the properties of metamaterial-based waveguides. We investigate
      plasmonic waveguides with dielectric cores and multilayer metal-dielectric
      claddings with hyperbolic dispersion. Without using any homogenization, we
      calculate the resonant eigenmodes of the finite-width cladding layers, and find
      agreement with the resonant features in the dispersion of the cladded waveguides.
      We show that at the resonant widths, the propagating modes of the waveguides are
      coupled to the cladding eigenmodes and hence, are strongly absorbed. By avoiding
      the resonant widths in the design of the actual waveguides, the strong absorption
      can be eliminated. 

PMID- 25969006
TI  - Characterization of surface acoustic waves by stroboscopic white-light
      interferometry.
AB  - We present phase-sensitive absolute amplitude measurements of surface acoustic
      wave fields obtained using a stroboscopic white-light interferometer. The data
      analysis makes use of the high resolution available in the measured
      interferometric phase data, enabling the characterization of the out-of-plane
      surface vibration fields in electrically excited microstructures with better than
      100 pm amplitude resolution. The setup uses a supercontinuum light source with
      tailored spectral properties for obtaining the high amplitude resolution. The
      duration of the light pulses is less than 300 ps to allow the detection of high
      frequencies. These capabilities enabled a detailed measurement of the focusing of
      surface acoustic waves by an annular interdigital transducer structure operating
      at 74 MHz, featuring a maximum vibration amplitude of 3 nm. 

PMID- 25969007
TI  - Multidimensional object acquisition by single-shot phase imaging with a coded
      aperture.
AB  - We propose a generalized framework for quantitatively acquiring multidimensional
      complex objects based on single-shot phase imaging with a coded aperture (SPICA).
      In multidimensional SPICA, a propagating field from a multidimensional complex
      object is sieved by a coded aperture, the sieved field is modulated by an optical
      element, which is called coding optics, and then the resultant field is captured
      by a monochrome image sensor. The original complex field is reconstructed from
      the single captured intensity image by a phase retrieval algorithm with a support
      constraint of the coded aperture and a sparsity-based reconstruction algorithm
      based on compressive sensing. We also present theoretical conditions for the
      proposed method. As a demonstration, we numerically verified an application of
      this generalized framework for single-shot acquisition of depth-variant
      multispectral objects. 

PMID- 25969008
TI  - Ultra-narrow linewidth DFB-laser with optical feedback from a monolithic confocal
      Fabry-Perot cavity.
AB  - We present a compact, ultra-narrow-linewidth semiconductor laser based on a 780
      nm distributed feedback diode laser optically self-locked to a mode of an
      external monolithic confocal Fabry-Perot resonator. We characterize spectral
      properties of the laser by measuring its frequency noise power spectral density.
      The white frequency noise levels at 5 Hz(2)/Hz above a Fourier frequency as small
      as 20 kHz. This noise level is more than five orders of magnitude smaller than
      the noise level of the same solitary diode laser without resonant optical
      feedback, and it is three orders of magnitude smaller than the noise level of a
      narrow linewidth, grating-based, extended-cavity diode laser. The corresponding
      Lorentzian linewidth of the laser with resonant optical feedback is 15.7 Hz at an
      output power exceeding 50 mW.

PMID- 25969009
TI  - Self-optimizing femtosecond semiconductor laser.
AB  - A self-optimizing approach to intra-cavity spectral shaping of external cavity
      mode-locked semiconductor lasers using edge-emitting multi-section diodes is
      presented. An evolutionary algorithm generates spectrally resolved phase- and
      amplitude masks that lead to the utilization of a large part of the net gain
      spectrum for mode-locked operation. Using these masks as a spectral amplitude and
      phase filter, a bandwidth of the optical intensity spectrum of 3.7 THz is
      achieved and Fourier-limited pulses of 216 fs duration are generated after
      further external compression. 

PMID- 25969010
TI  - Limited view reconstruction for differential phase-contrast computed tomography.
AB  - This paper describes an algebraic reconstruction algorithm that uses total
      variation (TV) regularization for differential phase contrast computed tomography
      (DPC-CT) using a limited number of views. In order to overcome over-flattening
      inherent in TV regularization, a two-step reconstruction process is used: we
      first reconstruct tomographic images of gradient refractive index from
      differential projections with TV regularization; these images are then used to
      compute tomographic images of refractive index by solving the Poisson equation.
      We incorporate TV regularization in the reconstruction process because the
      distribution of gradient refractive index is much more flattened than the
      refractive index. Simulations of the proposed method demonstrate that it can
      achieve satisfactory image quality from a much smaller number of projections than
      is required by the Nyquist sampling theorem. We experimentally prove the
      feasibility of the proposed method using dark field imaging optics at PF-14C
      beamline at the Photon Factory, KEK. The differential phase contrast projection
      data was experimentally acquired from a biological sample and DPC-CT images were
      reconstructed. We show that far fewer projections are needed when the proposed
      algorithm is used. 

PMID- 25969011
TI  - Graphene-based Y-branch laser in femtosecond laser written Nd:YAG waveguides.
AB  - We report on Q-switched waveguide lasers on the graphene-based crystalline Y
      branch platform. By applying direct femtosecond laser writing of Nd:YAG laser
      crystal, a surface waveguide splitter with Y-branch geometry has been fabricated
      with depressed cladding configuration. The Q-switched lasing operation at 1064 nm
      is achieved in transmission mode, by attaching a two-layer graphene on the
      resonator output mirror, as well as by using interaction between the evanescent
      field and a few-layer graphene that was positioned right above the Y-type
      waveguide. Q-switched laser with a maximum average power of 173 mW, pulse energy
      and duration of 63 nJ and 90 ns is obtained. This work opens a way for laser
      written crystalline devices as compact, direct-pump laser sources for diverse
      applications. 

PMID- 25969012
TI  - Demonstration of terabit-scale data transmission in silicon vertical slot
      waveguides.
AB  - We design and fabricate silicon vertical slot waveguides for terabit-scale data
      transmission. The designed silicon photonic device is composed of apodized
      grating couplers, strip waveguides, strip-to-slot/slot-to-strip mode converters,
      and slot waveguide. Tight light confinement in the nano-scale air slot region is
      achieved in the silicon vertical slot waveguide which features relatively lower
      nonlinearity compared to silicon strip waveguide. Using the fabricated silicon
      photonic devices, we first demonstrate ultra-wide bandwidth 1.8-Tbit/s data
      transmission through a 2-mm-long silicon vertical slot waveguide using 161
      wavelength-division multiplexing (WDM) channels each carrying 11.2-Gbit/s
      orthogonal frequency-division multiplexing (OFDM) 16-ary quadrature amplitude
      modulation (16-QAM) signal. All 161 WDM channels achieve bit-error rate (BER)
      less than 1e-3 after on-chip data transmission. We further demonstrate terabit
      scale data transmission through four silicon vertical slot waveguides with
      different lengths (1 mm, 2 mm, 3.1 mm, 12.2 mm). The optical signal-to-noise
      ratio (OSNR) penalties of data transmission through four silicon vertical slot
      waveguides are 1, 2, 3.2 and 4.5 dB at a BER of 1e-3, respectively. The obtained
      results indicate that the presented silicon vertical slot waveguide might be an
      alternative promising candidate facilitating chip-scale high-speed optical
      interconnections. 

PMID- 25969013
TI  - Achromatic and high-resolution full-field X-ray microscopy based on total
      reflection mirrors.
AB  - We developed an achromatic and high-resolution full-field X-ray microscope based
      on advanced Kirkpatrick-Baez mirror optics that comprises two pairs of elliptical
      mirrors and hyperbolic mirrors utilizing the total reflection of X-rays.
      Performance tests to investigate the spatial resolution and chromatic aberration
      were performed at SPring-8. The microscope clearly resolved the pattern with ~100
      nm feature size. Imaging the pattern by changing the X-ray energy revealed
      achromatism in the wide energy range of 8-11 keV. 

PMID- 25969014
TI  - Ultra-thin broadband nanostructured insulator-metal-insulator-metal plasmonic
      light absorber.
AB  - An ultra-thin nanostructured plasmonic light absorber with an insulator-metal
      insulator-metal (IMIM) architecture is designed and numerically studied. The IMIM
      structure is capable to absorb up to about 82.5% of visible light in a broad
      wavelength range of 300-750 nm. The absorption by the bottom metal is only 6% of
      that of the top metal. The results show that the IMIM architecture has weak
      dependence of the angle of the incident light. Interestingly, by varying the top
      insulator material the optical absorption spectrum can be shifted more than 180
      nm as compared to the conventional air-metal-insulator-metal structure. The IMIM
      structure can be applied for different plasmonic devices with improved
      performance. 

PMID- 25969015
TI  - Biological imaging with nonlinear photothermal microscopy using a compact
      supercontinuum fiber laser source.
AB  - Nonlinear photothermal microscopy is applied in the imaging of biological tissues
      stained with chlorophyll and hematoxylin. Experimental results show that this
      type of organic molecules, which absorb light but transform dominant part of the
      absorbed energy into heat, may be ideal probes for photothermal imaging without
      photochemical toxicity. Picosecond pump and probe pulses, with central
      wavelengths of 488 and 632 nm, respectively, are spectrally filtered from a
      compact supercontinuum fiber laser source. Based on the light source, a compact
      and sensitive super-resolution imaging system is constructed. Further more, the
      imaging system is much less affected by thermal blurring than photothermal
      microscopes with continuous-wave light sources. The spatial resolution of
      nonlinear photothermal microscopy is ~ 188 nm. It is ~ 23% higher than commonly
      utilized linear photothermal microscopy experimentally and ~43% than conventional
      optical microscopy theoretically. The nonlinear photothermal imaging technology
      can be used in the evaluation of biological tissues with high-resolution and
      contrast. 

PMID- 25969016
TI  - Bidirectional multiband radio-over-fiber system based on polarization
      multiplexing and wavelength reuse.
AB  - A polarization multiplexing technique based on phase-shift-induced polarization
      modulation-to-intensity modulation (PloM-to-IM) convertor and a Mach-Zehnder
      modulator (MZM) is proposed to generate multi-band signals. Successful
      transmission of the traditional radio frequency, microwave (MW) and millimeter
      wave (MMW) signals is simultaneously achieved. Meanwhile, the intensity-constant
      optical carrier (OC) is reused for upstream 25-km transmission. 

PMID- 25969017
TI  - Simultaneous optical tracking of multiple targets in a field of view greater than
      20 degrees .
AB  - A multi-target tracking system using a self-starting optical phase conjugator was
      developed in this study. This system generates phase conjugate light (PCL) in a
      Nd:YAG resonator. Accurate tracking capability with a beam wander of 120 MUrad
      and constant PCL generation were confirmed over a field of view greater than 20
      degrees . This field of view was expanded by means of collector optics positioned
      in front of the phase conjugator. The developed scheme enables automatic and
      simultaneous optical energy transfer to multiple distant targets by utilizing the
      unique properties of optical phase conjugation of automatic target tracking and
      pointing. 

PMID- 25969018
TI  - Optical half-adder and half-subtracter employing the Pockels effect.
AB  - The Pockels effect in periodically poled lithium niobate made it possible to
      switch optical signals between two orthogonal optical linear polarizations of the
      vertical and horizontal polarization states. Based on this effect, we
      demonstrated polarization-based binary optical logic gates: AND, and OR gates. By
      combining these basic gates with other polarization-based optical logic gates
      such as XOR gate accomplished in our previous researches, half-adder and half
      subtracter of digital signals with a high extinction ratio of about 10dB have
      been demonstrated in our experiment, which made it possible to run more complex
      logical calculus. 

PMID- 25969019
TI  - Sub-50-fs widely tunable Yb:CaYAlO(4) laser pumped by 400-mW single-mode fiber
      coupled laser diode.
AB  - Yb:CaYAlO(4) has been investigated spectroscopically and compared to better known
      Yb:CaGdAlO(4). It turns out that both materials show very similar spectroscopic
      parameters relevant to ultrafast lasers design. Employing single-mode fiber
      coupled 400-mW laser diode at 976 nm we measured pulses as short as 43 fs, and
      broad tunability of 40 nm with a simple single-prism setup.

PMID- 25969020
TI  - High efficiency frequency upconversion of photons carrying orbital angular
      momentum for a quantum information interface.
AB  - The orbital angular momentum (OAM) of light shows great potential in quantum
      communication. The transmission wavelength for telecom is usually around 1550 nm,
      while the common quantum information storage and processing devices based on
      atoms, ions or NV color centers are for photons in visible regime. Here we
      demonstrate a quantum information interface based on the frequency upconversion
      for photons carrying OAM states from telecom wavelength to visible regime by sum
      frequency generation with high quantum conversion efficiency. The infrared
      photons at 1558 nm carrying different OAM values were converted to the visible
      regime of 622.2 nm, and the OAM value of the signal photons was well preserved in
      the frequency upconversion process with pump beam in Gaussian profile. 

PMID- 25969021
TI  - Miniaturized Bragg-grating couplers for SiN-photonic crystal slabs.
AB  - We report on an experimental and theoretical investigation of an integrated Bragg
      like grating coupler for near-vertical scattering of light from photonic crystal
      waveguides with an ultra-small footprint of a few lattice constants only. Using
      frequency-resolved measurements, we find the directional properties of the
      scattered radiation and prove that the coupler shows a good performance over the
      complete photonic bandgap. The results compare well to analytical considerations
      regarding 1d-scattering phenomena as well as to FDTD simulations. 

PMID- 25969022
TI  - 360 degree viewable floating autostereoscopic display using integral photography
      and multiple semitransparent mirrors.
AB  - In this paper, we present a polyhedron-shaped floating autostereoscopic display
      viewable from 360 degrees using integral photography (IP) and multiple
      semitransparent mirrors. IP combined with polyhedron-shaped multiple
      semitransparent mirrors is used to achieve a 360 degree viewable floating three
      dimensional (3D) autostereoscopic display, having the advantage of being able to
      be viewed by several observers from various viewpoints simultaneously. IP is
      adopted to generate a 3D autostereoscopic image with full parallax property.
      Multiple semitransparent mirrors reflect corresponding IP images, and the
      reflected IP images are situated around the center of the polyhedron-shaped
      display device for producing the floating display. The spatial reflected IP
      images reconstruct a floating autostereoscopic image viewable from 360 degrees.
      We manufactured two prototypes for producing such displays and performed two sets
      of experiments to evaluate the feasibility of the method described above. The
      results of our experiments showed that our approach can achieve a floating
      autostereoscopic display viewable from surrounding area. Moreover, it is shown
      the proposed method is feasible to facilitate the continuous viewpoint of a whole
      360 degree display without flipping. 

PMID- 25969023
TI  - Postprocessing algorithms to minimize fixed-pattern artifact and reduce trigger
      jitter in swept source optical coherence tomography.
AB  - We propose methods to align interferograms affected by trigger jitter to a
      reference interferogram based on the information (amplitude/phase) at a fixed
      pattern noise location to reduce residual fixed-pattern noise and improve the
      phase stability of swept source optical coherence tomography (SS-OCT) systems.
      One proposed method achieved this by introducing a wavenumber shift (k-shift) in
      the interferograms of interest and searching for the k-shift that minimized the
      fixed-pattern noise amplitude. The other method calculated the relative k-shift
      using the phase information at the residual fixed-pattern noise location.
      Repeating this wavenumber alignment procedure for all A-lines of interest
      produced fixed-pattern noise free and phase stable OCT images. A system
      incorporating these correction routines was used for human retina OCT and Doppler
      OCT imaging. The results from the two methods were compared, and it was found
      that the intensity-based method provided better results. 

PMID- 25969024
TI  - Switchable and tunable microwave frequency multiplication based on a dual
      passband microwave photonic filter.
AB  - In this paper, a novel approach to implement switchable and tunable microwave
      frequency multiplication has been proposed and experimentally demonstrated. High
      order harmonics of microwave signal with external modulation technique can be
      selected by using a novel switchable dual-passband microwave photonic filter
      (MPF) based on a modified fiber Mach-Zehnder interferometer (FMZI) and a
      dispersive medium. By adjusting the polarization controllers in the modified
      FMZI, the passbands of the MPF can switch between lower frequency, higher
      frequency or dual-passband states, and by changing the length of the variable
      optical delay line (VODL) in the modified FMZI, the central frequencies of these
      passbands can also be tuned. Therefore, tunable and switchable microwave signal
      frequency multiplication can be achieved. The experimental results show that by
      modulating a driving signal with frequency of 2.5 GHz, a signal with frequency of
      7.5 GHz, which is three times of the driving frequency, the other one with the
      frequency of 15 GHz, which is six times of the driving frequency can be generated
      and freely switchable between two frequencies and dual frequency states by simply
      adjusting the polarization controllers in the modified FMZI. 

PMID- 25969025
TI  - Dressed-state realization of the transition from electromagnetically induced
      transparency to Autler-Townes splitting in superconducting circuits.
AB  - We investigate electromagnetically induced transparency (EIT) and Autler-Townes
      splitting (ATS) in a driven three-level superconducting artificial system which
      is a dressed-state system resulting from the coupling of a superconducting charge
      qubit (an artificial atom) and a transmission line resonator. In the frame of the
      dressed-state approach and steady-state approximation, we study the linear
      absorption of the dressed artificial system to a weak probe signal in depth. In
      light of the spectrum-decomposition method and some other restrictions, we obtain
      the explicit conditions for the dressed-state realization of EIT and ATS and
      present a corresponding "phase diagram". In contrast to usual bare systems, these
      conditions given in the dressed system have an extra dependency on the qubit
      resonator parameters. And by varying the qubit's Josephson coupling energy we
      demonstrate a transition from EIT to ATS. 

PMID- 25969026
TI  - Fast calculation of computer-generated hologram using run-length encoding based
      recurrence relation.
AB  - Computer-Generated Holograms (CGHs) can be generated by superimposing zoneplates.
      A zoneplate is a grating that can concentrate an incident light into a point.
      Since a zoneplate has a circular symmetry, we reported an algorithm that rapidly
      generates a zoneplate by drawing concentric circles using computer graphic
      techniques. However, random memory access was required in the algorithm and
      resulted in degradation of the computational efficiency. In this study, we
      propose a fast CGH generation algorithm without random memory access using run
      length encoding (RLE) based recurrence relation. As a result, we succeeded in
      improving the calculation time by 88%, compared with that of the previous work.

PMID- 25969027
TI  - Mapping the spectral phase of isolated attosecond pulses by extreme-ultraviolet
      emission spectrum.
AB  - An all-optical method is proposed for the measurement of the spectral phase of
      isolated attosecond pulses. The technique is based on the generation of extreme
      ultraviolet (XUV) radiation in a gas by the combination of an attosecond pulse
      and a strong infrared (IR) pulse with controlled electric field. By using a full
      quantum simulation, we demonstrate that, for particular temporal delays between
      the two pulses, the IR field can drive back to the parent ions the photoelectrons
      generated by the attosecond pulse, thus leading to the generation of XUV photons.
      It is found that the generated XUV spectrum is notably sensitive to the chirp of
      the attosecond pulse, which can then be reliably retrieved. A classical quantum
      path analysis is further used to quantitatively explain the main features
      exhibited in the XUV emission. 

PMID- 25969028
TI  - Phonon induced phase grating in quantum dot system.
AB  - Electromagnetically induced phase grating is theoretically investigated in the
      driven two-level quantum dot exciton system at the presence of the exciton-phonon
      interactions. Due to the phonon-induced coherent population oscillation, the
      dispersion and absorption spectra are sharply changed and the phase modulation is
      enhanced via the high refractive index with nearly-vanishing absorption, which
      could effectively diffract a weak probe light into the first-order direction with
      the help of a standing-wave control field. Moreover, the diffraction efficiency
      of the grating can be easily manipulated by controlling the Huang-Rhys factor
      representing the exciton-phonon coupling, the intensity and detuning of the
      control field, and the detuning of the probe field. The scheme we present has
      potential applications in the photon devices for optical-switching and optical
      imaging in the micro-nano solid-state system. 

PMID- 25969029
TI  - CW dual-frequency MOPA laser with frequency separation of 45 GHz.
AB  - A CW dual-frequency master oscillator power amplifier (MOPA) laser system with
      dozens of gigahertz (GHz) frequency separation is presented. The MOPA system
      consists of a monolithic microchip seed laser and a double-end pumped traveling
      wave power amplifier. The short length of seed laser cavity guarantees the seed
      signal with a large frequency separation (above 53 GHz) but low output power
      (below 247.8 mW). By adding a long and low-doped active medium laser amplifier
      stage, a significant increase in laser power and an improvement in beam quality
      are obtained. After fine temperature tuning of seed laser cavity for "spectra
      matching", a 2.40 W dual-frequency laser signal with 45 GHz frequency separation
      is achieved. 

PMID- 25969030
TI  - Radiation hard mode-locked laser suitable as a spaceborne frequency comb.
AB  - We report ground-level gamma and proton radiation tests of a passively mode
      locked diode-pumped solid-state laser (DPSSL) with Yb:KYW gain medium. A total
      gamma dose of 170 krad(H(2)O) applied in 5 days generates minor changes in
      performances while maintaining solitonic regime. Pre-irradiation specifications
      are fully recovered over a day to a few weeks timescale. A proton fluence of
      9.76.10(10) cm(-2) applied in few minutes shows no alteration of the laser
      performances. Furthermore, complete stabilization of the laser shows excellent
      noise properties. From our results, we claim that the investigated femtosecond
      DPSSL technology can be considered rad-hard and would be suitable for generating
      frequency combs compatible with long duration space missions.

PMID- 25969031
TI  - Modulated light transmission through a subwavelength slit at early stage.
AB  - We simulate the early dynamics of enhanced light transmission through a
      subwavelength metallic slit and find that the amplitude of the transmitted light
      can be modulated. To understand this novel phenomenon and underlying physics, we
      develop a new analytical model. The field of each light period is considered as
      an individual unit. Each field is partially transmitted through the slit as the
      first subunit. The portion reflected from the exit interface travels a round trip
      in the slit and then partially exits again as the second subunit. There may be a
      gap in time between these two subunits. This process repeats so as to produce a
      subunit train, which is verified by the simulation of an incident sinusoidal
      pulse of one light period. When the wave units are continuous, the superposition
      of the trains produces the observed light. While the round-trip time is an
      integer multiple of the light period, the modulation period is the same. Besides
      academic importance, this study may be applicable to photonics with short laser
      pulses. 

PMID- 25969032
TI  - Novel switching mode in a vertically aligned liquid crystal contact lens.
AB  - Liquid crystal (LC) contact lenses are emerging as an exciting technology for
      vision correction. A homeotropically (vertical) aligned LC lens is reported that
      offers improved optical quality and simplified construction techniques over
      previously reported LC contact lens designs. The lens has no polarization
      dependence in the off state and produces a continuous change in optical power of
      up to 2.00 +/- 0.25 D with a voltage applied. The variation in optical power
      results from the voltage-induced change in refractive index of the nematic LC
      layer, from 1.52 to a maximum of 1.72. One device substrate is treated with an
      alignment layer that is a mixture of planar and homeotropic polyimides, rubbed to
      induce a preferred director orientation in the switched state. Defects that could
      occur during switching are thus avoided and the lens exhibits excellent optical
      quality with a continuous variation in focal power. 

PMID- 25969033
TI  - Focus issue introduction: optical cooling and trapping.
AB  - The year 2015 is an auspicious year for optical science, as it is being
      celebrated as the International Year of Light and Light-Based Technologies. This
      Focus Issue of the journals Optics Express and Journal of the Optical Society of
      America B has been organized by the OSA Technical Group on Optical Cooling and
      Trapping to mark this occasion, and to highlight the most recent and exciting
      developments in the topics covered by the group. Together this joint Focus Issue
      features 32 papers, including both experimental and theoretical works, which span
      this wide range of activities. 

PMID- 25969034
TI  - Method for predicting whispering gallery mode spectra of spherical
      microresonators.
AB  - A full three-dimensional Finite-Difference Time-Domain (FDTD)-based toolkit is
      developed to simulate the whispering gallery modes of a microsphere in the
      vicinity of a dipole source. This provides a guide for experiments that rely on
      efficient coupling to the modes of microspheres. The resultant spectra are
      compared to those of analytic models used in the field. In contrast to the
      analytic models, the FDTD method is able to collect flux from a variety of
      possible collection regions, such as a disk-shaped region. The customizability of
      the technique allows one to consider a variety of mode excitation scenarios,
      which are particularly useful for investigating novel properties of optical
      resonators, and are valuable in assessing the viability of a resonator for
      biosensing. 

PMID- 25969035
TI  - Plasmonic-organic hybrid (POH) modulators for OOK and BPSK signaling at 40
      Gbit/s.
AB  - We report on high-speed plasmonic-organic hybrid Mach-Zehnder modulators
      comprising ultra-compact phase shifters with lengths as small as 19 um. Choosing
      an optimum phase shifter length of 29 um, we demonstrate 40 Gbit/s on-off keying
      (OOK) modulation with direct detection and a BER < 6 * 10(-4). Furthermore, we
      report on a 29 um long binary-phase shift keying (BPSK) modulator and show that
      it operates error-free (BER < 1 * 10(-10)) at data rates up to 40 Gbit/s and with
      an energy consumption of 70 fJ/bit.

PMID- 25969036
TI  - Pulse dynamics in carbon nanotube mode-locked fiber lasers near zero cavity
      dispersion.
AB  - We numerically and experimentally analyze the output characteristics and pulse
      dynamics of carbon nanotube mode-locked fiber lasers near zero cavity dispersion
      (from 0.02 to ~-0.02 ps(2)). We focus on such near zero dispersion cavities to
      reveal the dispersion related transition between different mode-locking regimes
      (such as soliton-like, stretched-pulse and self-similar regimes). Using our
      proposed model, we develop a nanotube-mode-locked fiber laser setup generating
      ~97 fs pulse which operates in the stretched-pulse regime. The corresponding
      experimental results and pulse dynamics are in good agreement with the numerical
      results. Also, the experimental results from soliton-like and self-similar
      regimes exhibit the same trends with simulations. Our study will aid design of
      different mode-locking regimes based on other new saturable absorber materials to
      achieve ultra-short pulse duration.

PMID- 25969037
TI  - Demonstration of simultaneous mode conversion and demultiplexing for mode and
      wavelength division multiplexing systems based on tilted few-mode fiber Bragg
      gratings.
AB  - We experimentally demonstrate mode conversion by exploiting optical reflection of
      tilted few-mode fiber Bragg grating (FM-FBG). Mode conversions from LP(01) mode
      to higher symmetric and asymmetric modes are achieved, and more than 99.5%
      conversion efficiency from LP(01) to LP(11) mode is obtained using a 1.6 degrees 
      tilted FM-FBG. Influences of the weakly tilted FM-FBG parameters on the property
      of mode conversion is analyzed and discussed. A simultaneous mode conversion and
      demultiplexing scheme for 4-mode * 3-wavelength multiplexing transmission is
      proposed and the modal crosstalk is analyzed based on the transmission spectra of
      the tilted FM-FBGs. The proposed approach shows potential applications in mode
      and wavelength division multiplexing communication systems.

PMID- 25969038
TI  - Polarization rotation and coupling between silicon waveguide and hybrid plasmonic
      waveguide.
AB  - We present a polarization rotation and coupling scheme that rotates a TE(0) mode
      in a silicon waveguide and simultaneously couples the rotated mode to a hybrid
      plasmonic (HP(0)) waveguide mode. Such a polarization rotation can be realized
      with a partially etched asymmetric hybrid plasmonic waveguide consisting of a
      silicon strip waveguide, a thin oxide spacer, and a metal cap made from copper,
      gold, silver or aluminum. Two implementations, one with and one without the
      tapering of the metal cap are presented, and different taper shapes (linear and
      exponential) are also analyzed. The devices have large 3 dB conversion bandwidths
      (over 200 nm at near infrared) and short length (< 5 MUm), and achieve a maximum
      coupling factor of ~ 78% with a linearly tapered silver metal cap.

PMID- 25969039
TI  - Effects of surface diffusion on high temperature selective emitters.
AB  - Using morphological and optical simulations of 1D tantalum photonic crystals at
      1200K, surface diffusion was determined to gradually reduce the efficiency of
      selective emitters. This was attributed to shifting resonance peaks and declining
      emissivity caused by changes to the cavity dimensions and the aperture width.
      Decreasing the structure's curvature through larger periods and smaller cavity
      widths, as well as generating smoother transitions in curvature through the
      introduction of rounded cavities, was found to alleviate this degradation. An
      optimized structure, that shows both high efficiency selective emissivity and
      resistance to surface diffusion, was presented. 

PMID- 25969040
TI  - Inclined-incidence hard-X-ray resonator with ultrahigh efficiency and resolution.
AB  - We report a high-efficiency hard-X-ray resonator with inclined-incidence
      geometry. A beam incident at 36.87 degrees  with respect to [3 1 0] excites Bragg
      back diffraction along (12 4 0) at 14.4388 keV for resonance in a Si-based
      resonator to produce intense resonance fringes. The experimental results showed
      the visibility enhanced by nearly 30 times compared with normal incidence. Also
      numerical calculations of the inclined-incidence resonator demonstrate ultrahigh
      efficiency and extremely narrow resolving power (sub-meV) with low background.
      This geometry surpasses the intrinsic limits of normal-incidence crystal-based
      resonators and enables ultrahigh-resolution X-ray optics for X-ray diffraction,
      spectroscopy, and imaging applications. 

PMID- 25969041
TI  - Optical true time delay unit for multi-beamforming.
AB  - An optical true time delay (TTD) unit capable of adding independent time delays
      to multiple RF signals is proposed, which can be used for multi-beamforming in
      both transmit and receive modes. In the proposed unit, N RF signals with
      different center frequencies are modulated on an optical frequency comb (OFC).
      After transmission through a dispersive element, the RF-modulated OFC is split
      into N paths. In each path, a comb line is selected by a tunable optical filter.
      Thanks to the chromatic dispersion of the dispersive element, independently
      controllable TTDs can be obtained in all paths. Then, a microwave photonic filter
      (MPF) is incorporated in each path, allowing a designated RF signal to undergo
      the TTD in that path. A proof-of-concept experiment is carried out. A two-path
      unit with a low-pass MPF in one path and a high-pass MPF in the other path is
      built. Controllable TTDs up to ~1.4 ns with a step of ~69 ps are demonstrated
      based on a 25-GHz-spacing OFC. In addition, a wideband multi-beam phased-array
      antenna system that can work in both transmit and receive modes is designed using
      the proposed TTD unit. 

PMID- 25969042
TI  - Extracting the phase information from atomic memory by intensity correlation
      measurement.
AB  - We demonstrate experimentally controlled storage and retrieval of the optical
      phase information in a higher-order interference scheme based on Raman process in
      (87)Rb atomic vapor cells. An interference pattern is observed in intensity
      correlation measurement between the write Stokes field and the delayed read
      Stokes field as the phase of the Raman write field is scanned. This result
      implies that the phase information of the Raman write field can be written into
      the atomic spin wave via Raman process in a high gain regime and subsequently
      read out via a spin-wave enhanced Raman process, thus achieving optical storage
      of phase information. This technique should find applications in optical phase
      image storage, holography and information processing.

PMID- 25969043
TI  - Realization of mutually unbiased bases for a qubit with only one wave plate:
      theory and experiment.
AB  - We consider the problem of implementing mutually unbiased bases (MUB) for a
      polarization qubit with only one wave plate, the minimum number of wave plates.
      We show that one wave plate is sufficient to realize two MUB as long as its phase
      shift (modulo 360 degrees ) ranges between 45 degrees  and 315 degrees . It can
      realize three MUB (a complete set of MUB for a qubit) if the phase shift of the
      wave plate is within [111.5 degrees , 141.7 degrees ] or its symmetric range with
      respect to 180 degrees . The systematic error of the realized MUB using a third
      wave plate (TWP) with 120 degrees  phase is calculated to be a half of that using
      the combination of a quarter-wave plate (QWP) and a half-wave plate (HWP). As
      experimental applications, TWPs are used in single-qubit and two-qubit quantum
      state tomography experiments and the results show a systematic error reduction by
      50%. This technique not only saves one wave plate but also reduces the systematic
      error, which can be applied to quantum state tomography and other applications
      involving MUB. The proposed TWP may become a useful instrument in optical
      experiments, replacing multiple elements like QWP and HWP. 

PMID- 25969044
TI  - Tracing the trajectory of photons through Fourier spectrum.
AB  - By slightly vibrating the mirrors in an interferometer at different frequencies,
      the photons' trajectory information is stored in the light beam. To read out this
      information, we record the centroid location of the intensity distribution of
      output beam and Fourier analyze its time evolution. It is shown that every
      vibrating mirror contributes a peak in the Fourier spectrum. In other words, we
      can reveal the trajectory of the photons by figuring out the vibrating mirrors
      which ever interact with the light beam based on the Fourier spectrum. This
      techniques is not limited by the vibration amplitude of the mirrors. 

PMID- 25969045
TI  - Development of time-domain differential Raman for transient thermal probing of
      materials.
AB  - A novel transient thermal characterization technology is developed based on the
      principles of transient optical heating and Raman probing: time-domain
      differential Raman. It employs a square-wave modulated laser of varying duty
      cycle to realize controlled heating and transient thermal probing. Very well
      defined extension of the heating time in each measurement changes the temperature
      evolution profile and the probed temperature field at MUs resolution. Using this
      new technique, the transient thermal response of a tipless Si cantilever is
      investigated along the length direction. A physical model is developed to
      reconstruct the Raman spectrum considering the temperature evolution, while
      taking into account the temperature dependence of the Raman emission. By fitting
      the variation of the normalized Raman peak intensity, wavenumber, and peak area
      against the heating time, the thermal diffusivity is determined as 9.17 * 10(-5),
      8.14 * 10(-5), and 9.51 * 10(-5) m(2)/s. These results agree well with the
      reference value of 8.66 * 10(-5) m(2)/s considering the 10% fitting uncertainty.
      The time-domain differential Raman provides a novel way to introduce transient
      thermal excitation of materials, probe the thermal response, and measure the
      thermal diffusivity, all with high accuracy.

PMID- 25969046
TI  - Physical-layer network coding in coherent optical OFDM systems.
AB  - We present the first experimental demonstration and characterization of the
      application of optical physical-layer network coding in coherent optical OFDM
      systems. It combines two optical OFDM frames to share the same link so as to
      enhance system throughput, while individual OFDM frames can be recovered with
      digital signal processing at the destined node. 

PMID- 25969047
TI  - Excitation of atoms in an optical lattice driven by polychromatic amplitude
      modulation.
AB  - We investigate the mutiphoton process between different Bloch states in an
      amplitude modulated optical lattice. In the experiment, we perform the modulation
      with more than one frequency components, which includes a high degree of freedom
      and provides a flexible way to coherently control quantum states. Based on the
      study of single frequency modulation, we investigate the collaborative effect of
      different frequency components in two aspects. Through double frequency
      modulations, the spectrums of excitation rates for different lattice depths are
      measured. Moreover, interference between two separated excitation paths is shown,
      emphasizing the influence of modulation phases when two modulation frequencies
      are commensurate. Finally, we demonstrate the application of the double frequency
      modulation to design a large-momentum-transfer beam splitter. The beam splitter
      is easy in practice and would not introduce phase shift between two arms. 

PMID- 25969048
TI  - Diode-pumped actively Q-switched Tm:YAP/BaWO(4) intracavity Raman laser.
AB  - We report an intracavity Raman laser based on BaWO(4) Raman conversion in a diode
      pumped actively Q-switched Tm:YAP laser for the first time. With an incident
      diode power of 17.5 W and a pulse repetition rate of 1 kHz, the maximum average
      output powers of 880 mW and 306 mW for the fundamental laser at 1.94 MUm and the
      first Stokes laser at 2.36 MUm were obtained, respectively. The pulse width and
      pulse energy of the first Stokes laser were 14.1 ns and 0.31 mJ, respectively.
      The Raman gain coefficient of the BaWO(4) crystal was estimated to be 1.1 cm/GW
      at 1.94 MUm.

PMID- 25969049
TI  - A multiple-resonator approach for broadband light absorption in a single layer of
      nanostructured graphene.
AB  - The interaction between two-dimensional (2D) materials and light is rather weak
      due to their ultrathin thickness. In order for these emerging 2D materials to
      achieve performances that are comparable to those of conventional optoelectronic
      devices, the light-material interaction must be significantly enhanced. An
      effective way to enhance the interaction is to use optical resonances. Efficient
      light absorption has been demonstrated in a single layer of graphene based on a
      variety of resonators. However, the bandwidth of the absorption enhancement is
      always narrow, which limits its application for optoelectronic devices. In order
      to broaden the enhancement of light-material interaction, here we propose a
      multiple-resonator approach based on nanostructured graphene. These
      nanostructures having different geometry support resonances at different
      frequencies. Owing to their deep subwavelength sizes, graphene resonators can be
      closely packed in space, resulting in a high optical density of states, which
      enables the broadband light absorption. 

PMID- 25969050
TI  - Spectral fringes in non-phase-matched SHG and refinement of dispersion relations
      in the VUV.
AB  - We consider second harmonic generation (SHG) of ultrashort pulses in the case of
      strong phase- and group-velocity mismatch. Spectral fringes appear in the second
      harmonic related to two delayed replicas of the fundamental pulse in the time
      domain. The fringe separation can be used to evaluate the group-velocity and
      refractive index of nonlinear crystals at extreme wavelengths. Experimental
      results with femtosecond pulses in SrB(4)O(7) (SBO) are used to refine the
      Sellmeier equation describing the n(c) refractive index down to 160 nm, essential
      for the use of this unique nonlinear crystal for random quasi-phase-matching in
      the VUV.

PMID- 25969051
TI  - Demonstration of a highly-sensitive tunable beam displacer with no use of beam
      deflection based on the concept of weak value amplification.
AB  - We report the implementation of a highly sensitive tunable beam displacer based
      on the concept of weak value amplification, that allows to displace the centroid
      of a Gaussian beam a distance much smaller than its beam width without the need
      to deflect the direction of propagation of the input beam with movable optical
      elements. The beam's centroid position can be displaced by controlling the linear
      polarization of the output beam, and the dependence between the centroid's
      position and the angle of polarization is linear. 

PMID- 25969052
TI  - 12 THz flat gain fiber optical parametric amplifiers with dispersion varying
      fibers.
AB  - We report a fiber-optic parametric amplifier with ultra-broad and flat gain band
      by using a longitudinally tailored optical fiber. The parametric amplifier has
      been designed from realistic numerical simulations combined with an inverse
      algorithm to obtain a flat and wide gain band through fiber dispersion
      management. We experimentally report ~12 THz gain bandwidth on the Stokes side of
      the pump with a gain ripple as low as 7 dB and a mean gain up to ~60 dB.
      Experimental results show good agreement with numerical predictions for different
      pump powers and wavelength detuning. 

PMID- 25969054
TI  - Repetition rate multiplication of femtosecond light pulses using a phase-locked
      all-pass fiber resonator.
AB  - We describe an all-pass fiber resonator with active phase-locking capability for
      accurate multiplication of the repetition rate of femtosecond light pulses. The
      cavity length of the resonator is precisely controlled using the Pounder-Drever
      Hall phase-locking technique so that the repetition rate is multiplied in
      stabilization to the Rb atomic clock. Our test result proves the proposed phase
      locking scheme is an effective means of generating higher repetition rate pulses
      with no significant power loss while providing a high degree of long-term
      stability. 

PMID- 25969053
TI  - Dual-comb self-mode-locked monolithic Yb:KGW laser with orthogonal polarizations.
AB  - The dependence of lasing threshold on the output transmission is numerically
      analyzed to find the condition for the gain-to-loss balance for the orthogonal Np
      and Nm polarizations with a Ng-cut Yb:KGW laser crystal. With the numerical
      analysis, an orthogonally polarized dual-comb self-mode-locked operation is
      experimentally achieved with a coated Yb:KGW crystal to form a monolithic cavity.
      At a pump power of 5.2 W, the average output power, the pulse repetition rate,
      and the pulse duration are measured to be 0.24 (0.6) W, 25.8 (25.3) GHz, and 1.06
      (1.12) ps for the output along the Np (Nm) polarization. 

PMID- 25969055
TI  - 24-W cryogenically cooled Nd:YAG monolithic 946-nm laser with a slope efficiency
      >70.
AB  - A high-power efficient monolithic Nd:YAG 946-nm laser is demonstrated at the
      cryogenic temperature. By exploring the absorption and the fluorescence spectra
      of the Nd:YAG crystal, it reveals the fact that the absorption bandwidth at 808
      nm is narrowing and the fluorescence intensity at 1061 nm is significant enhanced
      when the temperature is decreased. The temperature dependence of the lasing
      threshold at 946 nm is found to display a minimum value near a temperature of 170
      K. At an incident pump power of 34.5 W, the local heating leads the optimum
      temperature to be approximately 120 K and the maximum output power can reach 24.4
      W with the conversion efficiency of 71% as well as the slope efficiency up to
      75%. 

PMID- 25969056
TI  - High-energy, kHz, picosecond hybrid Yb-doped chirped-pulse amplifier.
AB  - We report on a diode-pumped, hybrid Yb-doped chirped-pulse amplification (CPA)
      laser system with a compact pulse stretcher and compressor, consisting of Yb
      doped fiber preamplifiers, a room-temperature Yb:KYW regenerative amplifier
      (RGA), and cryogenic Yb:YAG multi-pass amplifiers. The RGA provides a relatively
      broad amplification bandwidth and thereby a long pulse duration to mitigate B
      integral in the CPA chain. The ~1030-nm laser pulses are amplified up to 70 mJ at
      1-kHz repetition rate, currently limited by available optics apertures, and then
      compressed to ~6 ps with high efficiency. The near-diffraction-limited beam
      focusing quality is demonstrated with M(x)(2) = 1.1 and M(y)(2) = 1.2. The shot
      to-shot energy fluctuation is as low as ~1% (rms), and the long-term energy drift
      and beam pointing stability for over 8 hours measurement are ~3.5% and <6 MUrad
      (rms), respectively. To the best of our knowledge, this hybrid laser system
      produces the most energetic picosecond pulses at kHz repetition rates among rod
      type laser amplifiers. With an optically synchronized Ti:sapphire seed laser, it
      provides a versatile platform optimized for pumping optical parametric chirped
      pulse amplification systems as well as driving inverse Compton scattered X-rays.

PMID- 25969057
TI  - Ultra-high resolution Fourier domain optical coherence tomography for old master
      paintings.
AB  - In the last 10 years, Optical Coherence Tomography (OCT) has been successfully
      applied to art conservation, history and archaeology. OCT has the potential to
      become a routine non-invasive tool in museums allowing cross-section imaging
      anywhere on an intact object where there are no other methods of obtaining
      subsurface information. While current commercial OCTs have shown potential in
      this field, they are still limited in depth resolution (> 4 MUm in paint and
      varnish) compared to conventional microscopic examination of sampled paint cross
      sections (~1 MUm). An ultra-high resolution fiber-based Fourier domain optical
      coherence tomography system with a constant axial resolution of 1.2 MUm in
      varnish or paint throughout a depth range of 1.5 mm has been developed. While
      Fourier domain OCT of similar resolution has been demonstrated recently, the
      sensitivity roll-off of some of these systems are still significant. In contrast,
      this current system achieved a sensitivity roll-off that is less than 2 dB over a
      1.2 mm depth range with an incident power of ~1 mW on the sample. The high
      resolution and sensitivity of the system makes it convenient to image thin
      varnish and glaze layers with unprecedented contrast. The non-invasive 'virtual'
      cross-section images obtained with the system show the thin varnish layers with
      similar resolution in the depth direction but superior clarity in the layer
      interfaces when compared with conventional optical microscope images of actual
      paint sample cross-sections obtained micro-destructively. 

PMID- 25969058
TI  - Measuring optical transmission matrices by wavefront shaping.
AB  - We introduce a simple but practical method to measure the optical transmission
      matrix (TM) of complex media. The optical TM of a complex medium is obtained by
      modulating the wavefront of a beam impinging on the complex medium and imaging
      the transmitted full-field speckle intensity patterns. Using the retrieved TM, we
      demonstrate the generation and linear combination of multiple foci on demand
      through the complex medium. This method will be used as a versatile tool for
      coherence control of waves through turbid media. 

PMID- 25969059
TI  - Performance evolution of color cone lasing emissions in dye-doped cholesteric
      liquid crystals at different fabrication conditions.
AB  - This work investigates the performance evolution of color cone lasing emissions
      (CCLEs) based on dye-doped cholesteric liquid crystal (DDCLC) cells at different
      fabrication conditions. Experimental results show that the energy threshold
      (E(th)) and relative slope efficiency (eta(s)) of the lasing signal emitted at
      each cone angle (0 degrees -35 degrees ) in the CCLE decreases and increases,
      respectively, when the waiting time in a homogenously rubbed aligned DDCLC cell
      is increased from 0 hr to 216 hr (9 days). This result occurs because defect
      lines gradually shrink with the anchoring of the surface alignment when the
      waiting time is increased. Hence, the scattering loss decreases, and the dwelling
      time of the fluorescence photons in the resonator increases, which in turn
      enhances the CCLE performance. With the aligned cell given the pretreatment of a
      rapid annealing processing (RAP), the waiting time for obtaining an optimum CCLE
      can markedly be reduced sixfold. The surface alignment of the DDCLC cell also
      plays a necessary role in generating the CCLE. This work provides an insight into
      the temporal evolution of the performance for the CCLE laser and offers a method
      (RAP) of significantly speeding up the formation of a CCLE laser with optimum
      performance.

PMID- 25969060
TI  - Bragg gratings in a few mode microstructured polymer optical fiber in less than
      30 seconds.
AB  - We report the inscription of a Bragg grating in an undoped polymethylmethacrylate
      based microstructured fiber in a time record. The fiber has been irradiated with
      a 248 nm ultraviolet radiation, through the phase mask technique using low
      fluence and low repetition rate. The experimental conditions were chosen to
      modify the core refractive index of the fiber at the incubation regime and
      avoiding polymer ablation. The peak reflection of the Bragg grating was centered
      in the infrared region with 20 dB reflection and 0.16 nm bandwidth. These
      spectral properties are well attractive for sensors and communications
      applications. 

PMID- 25969061
TI  - Excitation of bound plasmons along nanoscale stripe waveguides: a comparison of
      end and grating coupling techniques.
AB  - In this paper we excite bound long range stripe plasmon modes with a highly
      focused laser beam. We demonstrate highly confined plasmons propagating along a
      50 um long silver stripe 750 nm wide and 30 nm thick. Two excitation techniques
      were studied: focusing the laser spot onto the waveguide end and focusing the
      laser spot onto a silver grating. By comparing the intensity of the out-coupling
      photons at the end of the stripe for both grating and end excitation we are able
      to show that gratings provide an increase of a factor of two in the output
      intensity and thus out-coupling of plasmons excited by this technique are easier
      to detect. Authors expect that the outcome of this paper will prove beneficial
      for the development of passive nano-optical devices based on stripe waveguides,
      by providing insight into the different excitation techniques available and the
      advantages of each technique. 

PMID- 25969062
TI  - Classification of peacock feather reflectance using principal component analysis
      similarity factors from multispectral imaging data.
AB  - Iridescent structural colors in biology exhibit sophisticated spatially-varying
      reflectance properties that depend on both the illumination and viewing angles.
      The classification of such spectral and spatial information in iridescent
      structurally colored surfaces is important to elucidate the functional role of
      irregularity and to improve understanding of color pattern formation at different
      length scales. In this study, we propose a non-invasive method for the spectral
      classification of spatial reflectance patterns at the micron scale based on the
      multispectral imaging technique and the principal component analysis similarity
      factor (PCASF). We demonstrate the effectiveness of this approach and its
      component methods by detailing its use in the study of the angle-dependent
      reflectance properties of Pavo cristatus (the common peacock) feathers, a species
      of peafowl very well known to exhibit bright and saturated iridescent colors. We
      show that multispectral reflectance imaging and PCASF approaches can be used as
      effective tools for spectral recognition of iridescent patterns in the visible
      spectrum and provide meaningful information for spectral classification of the
      irregularity of the microstructure in iridescent plumage. 

PMID- 25969063
TI  - Characterization of voltage-driven twisted nematic liquid crystal cell by dynamic
      polarization scanning ellipsometry.
AB  - A dynamic polarization scanning ellipsometry technique based on Stokes
      polarimetry is proposed for dynamically characterizing a voltage-driven twisted
      nematic liquid crystal (TNLC) cell. In the proposed method, the six effective
      ellipsometric parameters are extracted under modulation voltages ranging from 0 V
      ~ + 10 V using four linearly polarized input lights. The profiles of the tilt
      angle and twist angle are calculated as a function of the modulation voltage. The
      validity of the proposed method is confirmed by comparing the experimental
      results for the effective ellipsometric parameters of a TNLC cell with the
      analytical results. Furthermore, a genetic algorithm (GA) based on a curve
      fitting technique is used to inversely extract the pretilt angle, twist angle and
      rubbing direction of the TNLC cell. These extracted values are then compared to
      the known valued of the TNLC cell. In general, the results presented in this
      paper show that the proposed method provides a reliable means of obtaining the
      dynamic optical properties of a TNLC cell. 

PMID- 25969064
TI  - Efficient freeform lens optimization for computational caustic displays.
AB  - Phase-only light modulation shows great promise for many imaging applications,
      including future projection displays. While images can be formed efficiently by
      avoiding per-pixel attenuation of light most projection efforts utilizing phase
      only modulators are based on holographic principles which rely on interference of
      coherent laser light and a Fourier lens. Limitations of this type of an approach
      include scaling to higher power as well as visible artifacts such as speckle and
      image noise. We propose an alternative approach: operating the spatial phase
      modulator with broadband illumination by treating it as a programmable freeform
      lens. We describe a simple optimization approach for generating phase modulation
      patterns or freeform lenses that, when illuminated by a collimated, broadband
      light source, will project a pre-defined caustic image on a designated image
      plane. The optimization procedure is based on a simple geometric optics image
      formation model and can be implemented computationally efficient. We perform
      simulations and show early experimental results that suggest that the
      implementation on a phase-only modulator can create structured light fields
      suitable, for example, for efficient illumination of a spatial light modulator
      (SLM) within a traditional projector. In an alternative application, the
      algorithm provides a fast way to compute geometries for static, freeform lens
      manufacturing.

PMID- 25969065
TI  - Direct design of freeform surfaces and freeform imaging systems with a point-by
      point three-dimensional construction-iteration method.
AB  - In this paper, we proposed a general direct design method for three-dimensional
      freeform surfaces and freeform imaging systems based on a construction-iteration
      process. In the preliminary surfaces-construction process, the coordinates as
      well as the surface normals of the data points on the multiple freeform surfaces
      can be calculated directly considering the rays of multiple fields and different
      pupil coordinates. Then, an iterative process is employed to significantly
      improve the image quality or achieve a better mapping relationship of the light
      rays. Three iteration types which are normal iteration, negative feedback and
      successive approximation are given. The proposed construction-iteration method is
      applied in the design of an easy aligned, low F-number off-axis three-mirror
      system. The primary and tertiary mirrors can be fabricated on a single substrate
      and form a single element in the final system. The secondary mirror is simply a
      plane mirror. With this configuration, the alignment difficulty of a freeform
      system can be greatly reduced. After the preliminary surfaces-construction stage,
      the freeform surfaces in the optical system can be generated directly from an
      initial planar system. Then, with the iterative process, the average RMS spot
      diameter decreased by 75.4% compared with the system before iterations, and the
      maximum absolute distortion decreased by 94.2%. After further optimization with
      optical design software, good image quality which is closed to diffraction
      limited is achieved. 

PMID- 25969066
TI  - OAM states generation/detection based on the multimode interference effect in a
      ring core fiber.
AB  - In this paper, we propose to generate/detect orbital angular momentum (OAM)
      states based on the multimode interference (MMI) effect in a piece of ring core
      fiber. A comprehensive theory for the MMI process inside ring core fibers is
      presented. The MMI process inside ring core fibers will convert one input image
      into multiple equally spaced duplicated output images. After phase adjustment by
      a fixed phase shifter array, these output images will stimulate OAM states in the
      ring core fiber or in free space. Henceforth, a novel OAM multiplexer/de
      multiplexer (MUX/DEMUX) can be realized by a piece of ring core fiber and a fixed
      phase shifters array. 

PMID- 25969067
TI  - Dual optical role of low-index injection layers for efficient polarizer-free high
      contrast-ratio organic light-emitting diodes.
AB  - Polarizer-free high contrast-ratio organic light-emitting diodes (OLEDs) are
      explored with a structure involving a semi-reflective Cr-based bottom electrode
      and a dielectric-capped thin Ag top electrode. Their efficiency is shown to be
      improved significantly with little sacrifice in luminous reflectance by adopting
      low-refractive-index injection layers that can increase the effective reflectance
      from the bottom electrode and simultaneously reduce the loss owing to surface
      plasmon polariton modes. OLEDs employing a low-refractive-index injection layer
      exhibit improved current efficiency by up to ca. 27.4% than those using index
      matched injection layers, with luminous reflectance maintained at as low as 4%. 

PMID- 25969068
TI  - Control modulation instability in photorefractive crystals by the intensity ratio
      of background to signal fields.
AB  - By experimental measurements and theoretical analyses, we demonstrate the control
      of modulation instability in photorefractive crystals though the intensity ratio
      of coherent background to signal fields. Appearance, suppression, and
      disappearance of modulated stripes are observed in a series of spontaneous
      optical pattern formations, as the intensity of input coherent beam increases.
      Theoretical curves based on the band transport model give good agreement to
      experimental data, both for different bias voltages and different intensity
      ratios. 

PMID- 25969069
TI  - Metasurface for characterization of the polarization state of light.
AB  - The miniaturization of measurement systems currently used to characterize the
      polarization state of light is limited by the bulky optical components used such
      as polarizers and waveplates. We propose and experimentally demonstrate a simple
      and compact approach to measure the ellipticity and handedness of the polarized
      light using an ultrathin (40 nm) gradient metasurface. A completely polarized
      light beam is decomposed into a left circularly polarized beam and a right
      circularly polarized beam, which are steered in two directions by the metasurface
      consisting of nanorods with spatially varying orientations. By measuring the
      intensities of the refracted light spots, the ellipticity and handedness of
      various incident polarization states are characterized at a range of wavelengths
      and used to determine the polarization information of the incident beam. To fully
      characterize the polarization state of light, an extra polarizer can be used to
      measure the polarization azimuth angle of the incident light. 

PMID- 25969070
TI  - Unambiguous demonstration of soliton evolution in slow-light silicon photonic
      crystal waveguides with SFG-XFROG.
AB  - We demonstrate the temporal and spectral evolution of picosecond soliton in the
      slow light silicon photonic crystal waveguides (PhCWs) by sum frequency
      generation cross-correlation frequency resolved optical grating (SFG-XFROG) and
      nonlinear Schrodinger equation (NLSE) modeling. The reference pulses for the SFG
      XFROG measurements are unambiguously pre-characterized by the second harmonic
      generation frequency resolved optical gating (SHG-FROG) assisted with the
      combination of NLSE simulations and optical spectrum analyzer (OSA) measurements.
      Regardless of the inevitable nonlinear two photon absorption, high order soliton
      compressions have been observed remarkably owing to the slow light enhanced
      nonlinear effects in the silicon PhCWs. Both the measurements and the further
      numerical analyses of the pulse dynamics indicate that, the free carrier
      dispersion (FCD) enhanced by the slow light effects is mainly responsible for the
      compression, the acceleration, and the spectral blue shift of the soliton. 

PMID- 25969071
TI  - Local refractive index sensitivity of gold nanodisks.
AB  - We experimentally investigate the local refractive index sensitivity of plasmonic
      gold nanodisks by applying small polymer dots to selected disk sites by means of
      two-step lithography. Measured sensitivity profiles obtained from tracking the
      polymer-induced spectral shift of the plasmon modes are in excellent agreement
      with numerical simulation of both spectral sensitivity and the electric near
      field of the nanodisks. Based on the nanodisk sensitivity profile we tailor a
      sensitive and spatially uniform plasmonic sensor by capping the disk with a
      dielectric layer, thus restricting analyte access to the disk rim. 

PMID- 25969072
TI  - Remote estimation of phytoplankton size fractions using the spectral shape of
      light absorption.
AB  - Phytoplankton size structure plays an important role in ocean biogeochemical
      processes. The light absorption spectra of phytoplankton provide a great
      potential for retrieving phytoplankton size structure because of the strong
      dependence on the packaging effect caused by phytoplankton cell size and on
      different pigment compositions related to phytoplankton taxonomy. In this study,
      we investigated the variability in light absorption spectra of phytoplankton in
      relation to the size structure. Based on this, a new approach was proposed for
      estimating phytoplankton size fractions. Our approach use the spectral shape of
      the normalized phytoplankton absorption coefficient (a(ph)(lambda)) through
      principal component analysis (PCA). Values of a(ph)(lambda) were normalized to
      remove biomass effects, and PCA was conducted to separate the spectral variance
      of normalized a(ph)(lambda) into uncorrelated principal components (PCs).
      Spectral variations captured by the first four PC modes were used to build
      relationships with phytoplankton size fractions. The results showed that PCA had
      powerful ability to capture spectral variations in normalized a(ph)(lambda),
      which were significantly related to phytoplankton size fractions. For both
      hyperspectral a(ph)(lambda) and multiband a(ph)(lambda), our approach is
      applicable. We evaluated our approach using wide in situ data collected from
      coastal waters and the global ocean, and the results demonstrated a good and
      robust performance in estimating phytoplankton size fractions in various regions.
      The model performance was further evaluated by a(ph)(lambda) derived from in situ
      remote sensing reflectance (R(rs)(lambda)) with a quasi-analytical algorithm.
      Using R(rs)(lambda) only at six bands, accurate estimations of phytoplankton size
      fractions were obtained, with R(2) values of 0.85, 0.61, and 0.76, and root mean
      square errors of 0.130, 0.126, and 0.112 for micro-, nano-, and
      picophytoplankton, respectively. Our approach provides practical basis for remote
      estimation of phytoplankton size structure using a(ph)(lambda) derived from
      satellite observations or rapid field instrument measurements in the future.

PMID- 25969073
TI  - Single frequency microwave cloaking and subwavelength imaging with curved wired
      media.
AB  - We consider the cloaking properties of electromagnetic wired media deduced from
      arbitrary coordinate transformations. We propose an interpretation of
      invisibility via sub-wavelength imaging features. The quality of cloaking is
      assessed by the level of deformation of the image of a P-shaped source through
      the stretched wired media: the lesser the image deformation, the more effective
      the cloaking. We numerically and experimentally demonstrate a tetrahedral wired
      cloak with longer edge length about 7cm at a frequency of 1GHz (the cloak is thus
      subwavelength). The wired cloak has two functionalities: it can serve as a high
      resolution imaging system over long distances, and it can also perform space
      transformations such as, but not limited to, cloaking at a single operation
      frequency. 

PMID- 25969074
TI  - Incomplete immunity to backscattering in chiral one-way photonic crystals.
AB  - We show that the propagating modes in a strongly-guided chiral one-way photonic
      crystal are not backscattering-immune even though they are indeed insensitive to
      many kinds of scatters. Since these modes are not protected by the
      nonreciprocity, the backscattering does occur under certain circumstances. We use
      a perturbative method to derive criteria for the prominent backscattering in such
      chiral structures. From both our theory and numerical examinations, we find that
      the amount of backscattering critically depends on the symmetry of scatters.
      Additionally, for these chiral photonic modes, disturbances at the most intense
      parts of field profiles do not necessarily lead to the most effective
      backscattering. 

PMID- 25969075
TI  - Non-local effects in dual-probe-sideband Brillouin optical time domain analysis.
AB  - According to recent models, non-local effects in dual-probe-sideband Brillouin
      Optical Time Domain Analysis (BOTDA) systems should be essentially negligible
      whenever the probe power is below the Stimulated Brillouin Scattering (SBS)
      threshold. This paper shows that actually there appear non-local effects in this
      type of systems before the SBS threshold. To explain these effects it is
      necessary to take into account a full spectral description of the SBS process.
      The pump pulse experiences a frequency-dependent spectral deformation that
      affects the readout process differently in the gain and loss configurations. This
      paper provides a simple analytical model of this phenomenon, which is validated
      against compelling experimental data, showing good agreement. The main conclusion
      of our study is that the measurements in gain configuration are more robust to
      this non-local effect than the loss configuration. Experimental and theoretical
      results show that, for a total probe wave power of ~1 mW (500 MUW on each
      sideband), there is an up-shifting of ~1 MHz in the Brillouin Frequency Shift
      (BFS) retrieved from the Brillouin Loss Spectrum, whereas the BFS extracted from
      the measured Brillouin Gain Spectrum is up-shifted only ~0.6 MHz. These results
      are of particular interest for manufacturers of long-range BOTDA systems. 

PMID- 25969076
TI  - Temperature-independent fiber salinity sensor based on Fabry-Perot interference.
AB  - We present a novel fiber Fabry-Perot (FP) interference salinity sensor based on
      polyimide (PI) diaphragm. With an increase in water salinity, the PI diaphragm
      shrinks, and the PI diaphragm constriction causes the increase of the width of
      the air-gap, which causes the red shift of the interference fringes. We
      fabricated salinity sensor prototypes with different air-gap lengths and 20MUm PI
      diaphragm. When salinity increases from 0mol/L to 5.47mol/L, the maximum
      sensitivity is 0.45nm/(mol/L). We verify that the sensitivity can be enhanced by
      reducing air-gap cavity length. We also choose appropriate air cavity length and
      PI diaphragm length to solve the cross-sensitivity between temperature and
      salinity. As a robust and ultra-compact salinity sensor, which is easy to be
      fabricated and need no alignment, this fiber interferometer can be applied for
      real-time salinity sensing applications. 

PMID- 25969077
TI  - Perspectives and limitations of QKD integration in metropolitan area networks.
AB  - Quantum key distribution (QKD) systems have already reached a reasonable level of
      maturity. However, a smooth integration and a wide adoption of commercial QKD
      systems in metropolitan area networks has still remained challenging because of
      technical and economical obstacles. Mainly the need for dedicated fibers and the
      strong dependence of the secret key rate on both loss budget and background noise
      in the quantum channel hinder a practical, flexible and robust implementation of
      QKD in current and next-generation optical metro networks. In this paper, we
      discuss these obstacles and present approaches to share existing fiber
      infrastructures among quantum and classical channels. Particularly, a proposal
      for a smooth integration of QKD in optical metro networks, which implies removing
      spurious background photons caused by optical transmitters, amplifiers and
      nonlinear effects in fibers, is presented and discussed. We determine and
      characterize impairments on quantum channels caused by many classical telecom
      channels at practically used power levels coexisting within the same fiber.
      Extensive experimental results are presented and indicate that a practical
      integration of QKD in conventional optical metro networks is possible.

PMID- 25969078
TI  - Single photon transport along a one-dimensional waveguide with a side manipulated
      cavity QED system.
AB  - An external mirror coupling to a cavity with a two-level atom inside is put
      forward to control the photon transport along a one-dimensional waveguide. Using
      a full quantum theory of photon transport in real space, it is shown that the
      Rabi splittings of the photonic transmission spectra can be controlled by the
      cavity-mirror couplings; the splittings could still be observed even when the
      cavity-atom system works in the weak coupling regime, and the transmission
      probability of the resonant photon can be modulated from 0 to 100%. Additionally,
      our numerical results show that the appearance of Fano resonance is related to
      the strengths of the cavity-mirror coupling and the dissipations of the system.
      An experimental demonstration of the proposal with the current photonic crystal
      waveguide technique is suggested. 

PMID- 25969079
TI  - Effective wavelength scaling of rectangular aperture antennas.
AB  - We investigate the resonances of aperture antennas from the visible to the
      terahertz regime, with comparison to comprehensive simulations. Simple piecewise
      analytic behavior is found for the wavelength scaling over the entire spectrum,
      with a linear regime through the visible and near-IR. This theory will serve as a
      useful and simple design tool for applications including biosensors, nonlinear
      plasmonics and surface enhanced spectroscopies. 

PMID- 25969080
TI  - Realization of low-scattering metamaterial shell based on cylindrical wave
      expanding theory.
AB  - In this paper, we demonstrate the design of a low-scattering metamaterial shell
      with strong backward scattering reduction and a wide bandwidth at microwave
      frequencies. Low echo is achieved through cylindrical wave expanding theory, and
      such shell only contains one metamaterial layer with simultaneous low
      permittivity and permeability. Cut-wire structure is selected to realize the low
      electromagnetic (EM) parameters and low loss on the resonance brim region. The
      full-model simulations show good agreement with theoretical calculations, and
      illustrate that near -20dB reduction is achieved and the -10 dB bandwidth can
      reach up to 0.6 GHz. Compared with the cloak based on transformation
      electromagnetics, the design possesses advantage of simpler requirement of EM
      parameters and is much easier to be implemented when only backward scattering
      field is cared. 

PMID- 25969081
TI  - Short and robust silicon mode (de)multiplexers using shortcuts to adiabaticity.
AB  - Compact silicon mode (de)multiplexers based on asymmetrical directional couplers
      are designed using shortcuts to adiabaticity. The coupling coefficient and
      propagation constants mismatch are engineered to optimize the device robustness.
      Simulations show that the devices are broadband and have large fabrication
      tolerance. 

PMID- 25969082
TI  - Tunable optofluidic microring laser based on a tapered hollow core
      microstructured optical fiber.
AB  - A tunable optofluidic microring dye laser within a tapered hollow core
      microstructured optical fiber was demonstrated. The fiber core was filled with a
      microfluidic gain medium plug and axially pumped by a nanosecond pulse laser at
      532 nm. Strong radial emission and low-threshold lasing (16 nJ/pulse) were
      achieved. Lasing was achieved around the surface of the microfluidic plug. Laser
      emission was tuned by changing the liquid surface location along the tapered
      fiber. The possibility of developing a tunable laser within the tapered
      simplified hollow core microstructured optical fiber presents opportunities for
      developing liquid surface position sensors and biomedical analysis. 

PMID- 25969083
TI  - Noise-like pulse trapping in a figure-eight fiber laser.
AB  - We report on the trapping of noise-like pulse in a figure-eight fiber laser mode
      locked by nonlinear amplifier loop mirror (NALM). After achievement of noise-like
      vector pulse, it was found that the wavelength shift of the two resolved
      polarization components responsible for the pulse trapping was very sensitive to
      the cavity birefringence. By properly rotating the polarization controllers
      (PCs), the wavelength shift could be up to 4.8 nm, which is much larger than that
      of conventional soliton trapping. The observed results would shed some light on
      the fundamental physics of noise-like pulse as well as its vector features in
      fiber lasers. 

PMID- 25969084
TI  - Coherence enhanced intermittency in an optically injected semiconductor laser.
AB  - We report on the experimental observation of coherence enhancement of noise
      induced intermittency in a semiconductor laser subject to optical injection from
      another laser at the boundary of the frequency-locking regime. The intermittent
      switches between locked and unlocked states occur more regularly at a certain
      value of the injecting laser pump current. A shape of probability distribution of
      the experimental inter-spike-interval fluctuations is used to quantitatively
      characterize the intermittent behavior. 

PMID- 25969085
TI  - Comparative study of intracavity KTP-based Raman generation between Nd:YAP and
      Nd:YAG lasers operating on the (4)F(3/2) -> (4)I(13/2) transition.
AB  - Extending the spectral wavelengths of the diode-pumped Nd-doped lasers at 1.3 MUm
      with the KTP crystal in the intracavity Raman configuration is reported for the
      first time to the best of our knowledge. A systematic comparison is performed to
      show that a better optical conversion efficiency for the Nd:YAP/KTP Raman laser
      could be achieved thanks to the higher peak power and linearly polarized
      radiation at 1341 nm, whereas up to four Stokes emission lines are generated from
      the Nd:YAG/KTP Raman laser as a result of the fundamental dual-color operation at
      1319 and 1338 nm. The maximum Stokes output power of the developed Nd:YAP/KTP
      Raman laser reaches 1.04 W under an incident pump power of 16 W and a pulse
      repetition rate of 10 kHz, corresponding to the diode-to-Stokes conversion
      efficiency as high as 6.5%. The largest pulse energy and highest peak power are
      evaluated to be up to 104 MUJ and 34.7 kW, respectively. 

PMID- 25969086
TI  - Numerical investigation of the flat band Bloch modes in a 2D photonic crystal
      with Dirac cones.
AB  - A numerical method combining complex-k band calculations and absorbing boundary
      conditions for Bloch waves is presented. We use this method to study photonic
      crystals with Dirac cones. We demonstrate that the photonic crystal behaves as a
      zero-index medium when excited at normal incidence, but that the zero-index
      behavior is lost at oblique incidence due to excitation of modes on the flat
      band. We also investigate the formation of monomodal and multimodal cavity
      resonances inside the photonic crystals, and the physical origins of their
      different line-shape features. 

PMID- 25969087
TI  - Coherence modulation by deterministic rotating diffusers.
AB  - We design rotating diffusers with deterministic complex-amplitude transmission
      functions, which give rise to tailored spatial coherence modulation when
      transilluminated by an axially incident coherent Gaussian beam. Mathematical
      expressions are derived for the immediate diffuser output as well as for the far
      field response. An experimental demonstration is given using a diffuser
      fabricated by lithographic techniques. 

PMID- 25969088
TI  - Periodic inversion and phase transition of finite energy Airy beams in a medium
      with parabolic potential.
AB  - We study periodic inversion and phase transition of normal, displaced, and
      chirped finite energy Airy beams propagating in a parabolic potential. This
      propagation leads to an unusual oscillation: for half of the oscillation period
      the Airy beam accelerates in one transverse direction, with the main Airy beam
      lobe leading the train of pulses, whereas in the other half of the period it
      accelerates in the opposite direction, with the main lobe still leading - but now
      the whole beam is inverted. The inversion happens at a critical point, at which
      the beam profile changes from an Airy profile to a Gaussian one. Thus, there are
      two distinct phases in the propagation of an Airy beam in the parabolic potential
      - the normal Airy and the single-peak Gaussian phase. The length of the single
      peak phase is determined by the size of the decay parameter: the smaller the
      decay, the smaller the length. A linear chirp introduces a transverse
      displacement of the beam at the phase transition point, but does not change the
      location of the point. A quadratic chirp moves the phase transition point, but
      does not affect the beam profile. The two-dimensional case is discussed briefly,
      being equivalent to a product of two one-dimensional cases. 

PMID- 25969089
TI  - On the convergence and accuracy of the FDTD method for nanoplasmonics.
AB  - Use of the Finite-Difference Time-Domain (FDTD) method to model nanoplasmonic
      structures continues to rise - more than 2700 papers have been published in 2014
      on FDTD simulations of surface plasmons. However, a comprehensive study on the
      convergence and accuracy of the method for nanoplasmonic structures has yet to be
      reported. Although the method may be well-established in other areas of
      electromagnetics, the peculiarities of nanoplasmonic problems are such that a
      targeted study on convergence and accuracy is required. The availability of a
      high-performance computing system (a massively parallel IBM Blue Gene/Q) allows
      us to do this for the first time. We consider gold and silver at optical
      wavelengths along with three "standard" nanoplasmonic structures: a metal sphere,
      a metal dipole antenna and a metal bowtie antenna - for the first structure
      comparisons with the analytical extinction, scattering, and absorption
      coefficients based on Mie theory are possible. We consider different ways to set
      up the simulation domain, we vary the mesh size to very small dimensions, we
      compare the simple Drude model with the Drude model augmented with two critical
      points correction, we compare single-precision to double-precision arithmetic,
      and we compare two staircase meshing techniques, per-component and uniform. We
      find that the Drude model with two critical points correction (at least) must be
      used in general. Double-precision arithmetic is needed to avoid round-off errors
      if highly converged results are sought. Per-component meshing increases the
      accuracy when complex geometries are modeled, but the uniform mesh works better
      for structures completely fillable by the Yee cell (e.g., rectangular
      structures). Generally, a mesh size of 0.25 nm is required to achieve convergence
      of results to ~ 1%. We determine how to optimally setup the simulation domain,
      and in so doing we find that performing scattering calculations within the near
      field does not necessarily produces large errors but reduces the computational
      resources required. 

PMID- 25969090
TI  - Travelling-wave Mach-Zehnder modulators functioning as optical isolators.
AB  - On-chip optical isolators not requiring the use of magneto-optical materials has
      become a long-standing challenge in integrated optics. Here, we demonstrate that
      a traditional travelling-wave modulator can effectively function as an optical
      isolator, when driven under a prescribed modulation condition. By using an off
      shelve lithium niobate modulator, we achieve more than 12.5 dB isolation over an
      11.3-THz bandwidth at telecommunication wavelengths with a fiber-to-fiber
      insertion loss of 5.5 dB, by employing only a single radio-frequency drive
      signal. We also verify that the proposed active isolator can be functional in a
      laser system to effectively prevent instability due to strong back reflections.
      Since travelling-wave modulators are common devices in III-V and silicon
      photonics, our simple but efficient architecture may provide a practical solution
      to non-reciprocal light routing in photonic integrated circuits. 

PMID- 25969091
TI  - Experimental investigation of thermal effects and PCT on FBGs-based linearly
      polarized fiber laser performance.
AB  - We experimentally study the impacts of thermal effects and polarization crosstalk
      (PCT) on the performance of FBGs-based linearly polarized all-fiber laser. The
      mechanism that the thermal effects and PCT influence the performance of the laser
      is analyzed. Thermally-dependent reflection peaks of polarization maintaining
      (PM) fiber Bragg gratings are revealed to be the prime reason why temperature
      influences spectrum, output power, and polarization property of the laser. The
      PCT would also influence the performance of the laser seriously in the case of
      mismatched angle even with effectively overlapped spectrum. It is revealed
      experimentally that stable linearly polarized output can be obtained if a certain
      pair of aligned principal axes of PM FBGs is not only spectrally overlapped but
      also strictly angle matched. Further, we point out that accurate temperature
      control and careful angle match are essential for stable linearly polarized
      output and even possible power scaling further. 

PMID- 25969092
TI  - High-speed flow microscopy using compressed sensing with ultrafast laser pulses.
AB  - We demonstrate an imaging system employing continuous high-rate photonically
      enabled compressed sensing (CHiRP-CS) to enable efficient microscopic imaging of
      rapidly moving objects with only a few percent of the samples traditionally
      required for Nyquist sampling. Ultrahigh-rate spectral shaping is achieved
      through chirp processing of broadband laser pulses and permits ultrafast
      structured illumination of the object flow. Image reconstructions of high-speed
      microscopic flows are demonstrated at effective rates up to 39.6 Gigapixel/sec
      from a 720-MHz sampling rate. 

PMID- 25969093
TI  - All-optical tunable multilevel amplitude regeneration based on coherent wave
      mixing using a polarizer.
AB  - We describe and demonstrate an all-optical tunable phase- preserving scheme for
      multilevel amplitude regeneration based on coherent optical wave mixing using a
      polarizer for optical star 8-quadrature-amplitude modulation (star-8QAM) and star
      16QAM signals with a power ratio of 1:5. Amplitude noise can be efficiently
      suppressed on both amplitude levels. A regeneration factor of nearly 5 for the
      higher-amplitude level of star-8QAM and 3 for lower-amplitude level are achieved.
      The system robustness against nonlinear phase noise originating from the Gordon
      Mollenauer effect in a 150 km transmission line is investigated using the
      proposed amplitude regenerator. 

PMID- 25969094
TI  - Accurate calibration of S(2) and interferometry based multimode fiber
      characterization techniques.
AB  - We present a novel method to validate the relative amount of power carried by
      high order modes in a multimode fiber using a Spatial and Spectral (S(2)) imaging
      technique. The method can be utilized to calibrate the S(2) set-up and uses
      Fresnel reflections from a thin glass plate to compare theoretical values with
      experimental results. We have found that, in the most general case, spectral
      leakage and sampling errors can lead S(2) to underestimate the multipath
      interference (MPI) of high order modes by several decibels, thus significantly
      impairing the result of the measurement. On the other hand, by applying suitable
      corrections as described in this work, we demonstrate that the S(2) produces MPI
      estimates that are accurate to within 1dB or better.

PMID- 25969095
TI  - Design of a family of ring-core fibers for OAM transmission studies.
AB  - We propose a family of ring-core fibers, designed for the transmission of OAM
      modes, that can be fabricated by drawing five different fibers from a single
      preform. This novel technique allows us to experimentally sweep design parameters
      and speed up the fiber design optimization process. Such a family of fibers could
      be used to examine system performance, but also facilitate understanding of
      parameter impact in the transition from design to fabrication. We present design
      parameters characterizing our fiber, and enumerate criteria to be satisfied. We
      determine targeted fiber dimensions and explain our strategy for examining a
      design family rather than a single fiber design. We simulate modal properties of
      the designed fibers, and compare the results with measurements performed on
      fabricated fibers. 

PMID- 25969096
TI  - 300-mW narrow-linewidth deep-ultraviolet light generation at 193 nm by frequency
      mixing between Yb-hybrid and Er-fiber lasers.
AB  - A narrow-linewidth, high average power deep-ultraviolet (DUV) coherent laser
      emitting at 193 nm is demonstrated by frequency mixing a Yb-hybrid laser with an
      Er-fiber laser. The Yb-hybrid laser consists of Yb-fiber lasers and an Yb:YAG
      amplifier. The average output power of the 193 nm laser is 310 mW at 6 kHz, which
      corresponds to a pulse energy of 51 MUJ. To the best of our knowledge, this is
      the highest average power and pulse energy ever reported for a narrow-linewidth
      193 nm light generated by a combination of solid-state and fiber lasers with
      frequency mixing. We believe this laser will be beneficial for the application of
      interference lithography by seeding an injection-locking ArF eximer laser. 

PMID- 25969097
TI  - Process calibration method for designing silicon-on-insulator contra-directional
      grating couplers.
AB  - We present a process calibration method for designing silicon-on-insulator (SOI)
      contra-directional grating couplers (contra-DCs). Our method involves determining
      the coupling coefficients of fabricated contra-DCs by using their full-width-at
      half-maximum (FWHM) bandwidths. As compared to the null method that uses the
      bandwidth measured at the first nulls, our FWHM method obtains more consistent
      results since the FWHM bandwidth is more easily determined. We also extract the
      coupling coefficients using curve-fitting which provide values that are in
      general agreement with the values obtained using our method. However, as compared
      to the curve-fitting method, our method does not require knowledge of the
      insertion loss and is easier to implement. Our method can be used to predict the
      FWHM bandwidths, the maximum power coupling factors, the minimum power
      transmission factors, and the through port group delays and dispersions of
      subsequent, fabricated devices, which is useful in designing filters. 

PMID- 25969098
TI  - Light scattering from laser induced pit ensembles on high power laser optics.
AB  - Far-field light scattering characteristics from randomly arranged shallow
      Gaussian-like shaped laser induced pits, found on optics exposed to high energy
      laser pulses, is studied. Closed-form expressions for the far-field intensity
      distribution and scattered power are derived for individual pits and validated
      using numerical calculations of both Fourier optics and FDTD solutions to
      Maxwell's equations. It is found that the scattered power is proportional to the
      square of the pit width and approximately also to the square of the pit depth,
      with the proportionality factor scaling with pit depth. As a result, the power
      scattered from shallow pitted optics is expected to be substantially lower than
      assuming complete scattering from the total visible footprint of the pits. 

PMID- 25969099
TI  - Suspended 2-D photonic crystal aluminum nitride membrane reflector.
AB  - We experimentally demonstrated a free-standing two-dimensional (2-D) photonic
      crystal (PhC) aluminum nitride (AlN) membrane to function as a free space (or out
      of-plane) reflector working in the mid infrared region. By etching circular holes
      of radius 620nm in a 330nm thick AlN slab, greater than 90% reflection was
      measured from 3.08MUm to 3.78MUm, with the peak reflection of 96% at 3.16MUm. Due
      to the relatively low refractive index of AlN, we also investigated the
      importance of employing methods such as sacrificial layer release to enhance the
      performance of the PhC. In addition, characterization of the AlN based PhC was
      also done up to 450 degrees C to examine the impact of thermo-optic effect on the
      performance. Despite the high temperature operation, the redshift in the peak
      reflection wavelengths of the device was estimated to be only 14.1nm. This
      equates to a relatively low thermo-optic coefficient 2.22 * 10(-5) K(-1) for AlN.
      Such insensitivity to thermo-optic effect makes AlN based 2-D PhC a promising
      technology to be used as photonic components for high temperature applications
      such as Fabry-Perot interferometer used for gas sensing in down-hole oil drilling
      and ruggedized electronics.

PMID- 25969100
TI  - In-field Raman amplification on coherent optical fiber links for frequency
      metrology.
AB  - Distributed Raman amplification (DRA) is widely exploited for the transmission of
      broadband, modulated signals used in data links, but not yet in coherent optical
      links for frequency metrology, where the requirements are rather different. After
      preliminary tests on fiber spools, in this paper we deeper investigate Raman
      amplification on deployed in-field optical metrological links. We actually test a
      Doppler-stabilized optical link both on a 94 km-long metro-network implementation
      with multiplexed ITU data channels and on a 180 km-long dedicated fiber haul
      connecting two cities, where DRA is employed in combination with Erbium-doped
      fiber amplification (EDFA). The performance of DRA is detailed in both
      experiments, indicating that it does not introduce noticeable penalties for the
      metrological signal or for the ITU data channels. We hence show that Raman
      amplification of metrological signals can be compatible with a wavelength
      division multiplexing architecture and that it can be used as an alternative or
      in combination with dedicated bidirectional EDFAs. No deterioration is noticed in
      the coherence properties of the delivered signal, which attains frequency
      instability at the 10(-19) level in both cases. This study can be of interest
      also in view of the undergoing deployment of continental fiber networks for
      frequency metrology.

PMID- 25969101
TI  - Modulation stability analysis of exact multidimensional solutions to the
      generalized nonlinear Schrodinger equation and the Gross-Pitaevskii equation
      using a variational approach.
AB  - We analyze the modulation stability of spatiotemporal solitary and traveling wave
      solutions to the multidimensional nonlinear Schrodinger equation and the Gross
      Pitaevskii equation with variable coefficients that were obtained using Jacobi
      elliptic functions. For all the solutions we obtain either unconditional
      stability, or a conditional stability that can be furnished through the use of
      dispersion management. 

PMID- 25969102
TI  - Spline based iterative phase retrieval algorithm for X-ray differential phase
      contrast radiography.
AB  - Differential phase contrast imaging using grating interferometer is a promising
      alternative to conventional X-ray radiographic methods. It provides the
      absorption, differential phase and scattering information of the underlying
      sample simultaneously. Phase retrieval from the differential phase signal is an
      essential problem for quantitative analysis in medical imaging. In this paper, we
      formalize the phase retrieval as a regularized inverse problem, and propose a
      novel discretization scheme for the derivative operator based on B-spline
      calculus. The inverse problem is then solved by a constrained regularized
      weighted-norm algorithm (CRWN) which adopts the properties of B-spline and
      ensures a fast implementation. The method is evaluated with a tomographic dataset
      and differential phase contrast mammography data. We demonstrate that the
      proposed method is able to produce phase image with enhanced and higher soft
      tissue contrast compared to conventional absorption-based approach, which can
      potentially provide useful information to mammographic investigations. 

PMID- 25969103
TI  - Morphology dependent polymeric capillary optical resonator hydrostatic pressure
      sensor.
AB  - A hydrostatic pressure sensor based on morphology dependent resonances in a
      polymeric tube is presented. By internal pressurization, normal tensions will
      increase the device's size and shrink its wall thickness, inducing a shift in the
      resonant wavelengths of the resonator. Numerical simulations indicate that there
      are two modal regimes of sensitivity and a maximum achievable sensitivity,
      related to the device's geometry, constitutive material and analysed mode order.
      A sensitivity as high as 0.36 +/- 0.01 nm/bar has been experimentally found for a
      1.8mm diameter PMMA tube with wall thickness of 80um. 

PMID- 25969104
TI  - Extraction of linear anisotropic parameters using optical coherence tomography
      and hybrid Mueller matrix formalism.
AB  - A method is proposed for extracting the linear birefringence (LB) and linear
      dichroism (LD) properties of an anisotropic optical sample using reflection-mode
      optical coherence tomography (OCT) and a hybrid Mueller matrix formalism. To
      ensure the accuracy of the extracted parameter values, a method is proposed for
      calibrating and compensating the polarization distortion effect induced by the
      beam splitters in the OCT system using a composite quarter-waveplate / half
      waveplate / quarter-waveplate structure. The validity of the proposed method is
      confirmed by extracting the LB and LD properties of a quarter-wave plate and a
      defective polarizer. To the best of the authors' knowledge, the method proposed
      in this study represents the first reported attempt to utilize an inverse Mueller
      matrix formalism and a reflection-mode OCT structure to extract the LB and LD
      parameters of optically anisotropic samples. 

PMID- 25969105
TI  - Phase retrieval method for in-line phase contrast x-ray imaging and denoising by
      regularization.
AB  - Phase contrast X-ray imaging is increasingly popular in the past decade. In order
      to acquire phase contrast X-ray images, different types of imaging mechanisms
      have been proposed. Among them, in-line phase contrast X-ray imaging shows the
      highest potential because of its simplicity. In the study of in-line phase
      contrast imaging, based on different physical assumptions, many non-iterative
      phase retrieval methods, such as Bronnikov method, modified Bronnikov method,
      phase-attenuation duality (PAD) method, single-material method, and two-material
      method have been proposed. The main step of the non-iterative methods is a
      filtering process, thus different methods involve different filter design. In
      this paper we showed that every filter applied in the methods listed above is
      indeed the minimizer of a L(2)-norm regularization problem. In addition, two
      methods were proposed to overcome the over smoothing problem owing to the nature
      of L(2)-norm regularization.

PMID- 25969106
TI  - Theory of effect of near-infrared laser polarization direction on high-order
      terahertz sideband generation in semiconductors.
AB  - In a semiconductor illuminated by a strong terahertz (THz) field, the electron
      hole pairs excited by linear polarized near-infrared (NIR) laser can recombine to
      emit high-order THz sideband. Previous experimental results have shown, under the
      same condition of excitation intensity, the polarization direction of the NIR
      laser could affect the sideband intensity. In this letter, we theoretically
      investigate the effect of the NIR laser polarization direction on high-order
      terahertz sideband generation in bulk GaAs. 

PMID- 25969107
TI  - Ultrafast molecular orbital imaging based on attosecond photoelectron
      diffraction.
AB  - We present ab initio numerical study of ultrafast ionization dynamics of H(2)(+)
      as well as CO(2) and N(2) exposed to linearly polarized attosecond extreme
      ultraviolet pulses. When the molecules are aligned perpendicular to laser
      polarization direction, photonionization of these molecules show clear and
      distinguishing diffraction patterns in molecular attosecond photoelectron
      momentum distributions. The internuclear distances of the molecules are related
      to the position of the associated diffraction patterns, which can be determined
      with high accuracy. Moreover, the relative heights of the diffraction fringes
      contain fruitful information of the molecular orbital structures. We show that
      the diffraction spectra can be well produced using the two-center interference
      model. By adopting a simple inversion algorithm which takes into account the
      symmetry of the initial molecular orbital, we can retrieve the molecular orbital
      from which the electron is ionized. Our results offer possibility for imaging of
      molecular structure and orbitals by performing molecular attosecond photoelectron
      diffraction.

PMID- 25969108
TI  - Analysis of mirror soft-x-ray-EUV scattering using generalized continuous growth
      model of multiscale reliefs.
AB  - Combined computer simulations of the growth of multilayer mirrors and their exact
      differential reflection coefficients in the soft-x-ray-EUV range have been
      conducted. The proposed model describes the variation of the surface roughness of
      the multilayer Al/Zr mirror boundary profiles taking into account a random noise
      source. Theoretically calculated Al/Zr boundary profiles allow one to know real
      rough boundary statistics including rms roughnesses and correlation lengths and,
      to obtain rigorously EUV specular and diffuse reflection coefficients. The
      proposed integrated approach opens up a way to performing exact theoretical
      studies similar in accuracy to results obtained by quantitative microscopy
      investigations of nanoreliefs and synchrotron radiation measurements. 

PMID- 25969109
TI  - Imaging properties of extended depth of field microscopy through single-shot
      focus scanning.
AB  - Although the single-shot focus scanning technique (SSFS) has been experimentally
      demonstrated for extended depth of field (EDOF) imaging, few work has been
      performed to characterize its imaging properties and limitations. In this paper,
      based on an analytical model of a SSFS system, we examined the properties of the
      system response and the restored image quality in relation to the axial position
      of the object, scan range, and signal-to-noise ratio, and demonstrated the
      properties via a prototype of 10 * 0.25 NA microscope system. We quantified the
      full range of the achievable EDOF is equivalent to the focus scan range. We
      further demonstrated that the restored image quality can be improved by extending
      the focus scan range by a distance equivalent to twice of the standard DOF. For
      example, in a focus-scanning microscope with a +/- 15 MUm standard DOF, a 120 MUm
      focus scan range can obtain a +/- 60 MUm EDOF, but a 150 MUm scan range affords
      noticeably better EDOF images for the same EDOF range. These results provide
      guidelines for designing and implementing EDOF systems using SSFS technique. 

PMID- 25969110
TI  - On-fiber plasmonic interferometer for multi-parameter sensing.
AB  - We demonstrate a novel miniature multi-parameter sensing device based on a
      plasmonic interferometer fabricated on a fiber facet in the optical communication
      wavelength range. This device enables the coupling between surface plasmon
      resonance and plasmonic interference in the structure, which are the two
      essential mechanisms for multi-parameter sensing. We experimentally show that
      these two mechanisms have distinctive responses to temperature and refractive
      index, rendering the device the capability of simultaneous temperature and
      refractive index measurement on an ultra-miniature form factor. A high refractive
      index sensitivity of 220 nm per refractive index unit (RIU) and a high
      temperature sensitivity of -60 pm/  degrees C is achieved with our device. 

PMID- 25969111
TI  - InP monolithically integrated coherent transmitter.
AB  - A novel InP monolithically integrated coherent transmitter has been designed,
      fabricated and tested. The photonic integrated circuit consists of a distributed
      Bragg reflector laser and a modified nested Mach-Zehnder modulator having tunable
      input power splitters. Back-to-back coherent transmission for PDM-QPSK signals is
      reported up to 10 Gbaud (40 Gb/s) using the integrated laser and up to 32Gbaud
      (128 Gb/s) using an external low phase noise laser. 

PMID- 25969112
TI  - Different polarization dynamic states in a vector Yb-doped fiber laser.
AB  - Different polarization dynamic states in an unidirectional, vector, Yb-doped
      fiber ring laser have been observed. A rich variety of dynamic states, including
      group velocity locked polarization domains and their splitting into regularly
      distributed multiple domains, polarization locked square pulses and their
      harmonic mode locking counterparts, and dissipative soliton resonances have all
      been observed with different operating parameters. We have also shown
      experimentally details of the conditions under which polarization-domain-wall
      dark pulses and bright square pulses form. 

PMID- 25969113
TI  - Vibrational phase imaging in wide-field CARS for nonresonant background
      suppression.
AB  - Coherent Anti-Stokes Raman Scattering (CARS) microscopy is a valuable tool for
      label-free imaging of biological samples. As a major drawback quantification
      based on CARS images is compromised by the appearance of a nonresonant
      background. In this paper we propose and demonstrate a wide-field CARS
      vibrational phase imaging scheme that allows for nonresonant background
      suppression. Several CARS images at a few consecutive planes perpendicular to the
      propagation direction were recorded to reconstruct a phase map utilizing the
      iteration phase retrieval method. Experimental results verify that the CARS
      background is efficiently suppressed by the phase imaging approach, as compared
      to traditional CARS imaging without background correction. The proposed
      background correction method is robust against environmental disturbance, since
      the experimental implementation of the suggested detection scheme requires no
      reference beam. 

PMID- 25969114
TI  - Graphene decorated microfiber for ultrafast optical modulation.
AB  - We demonstrate ultrafast optical modulation using a single 1-MUm-diameter
      graphene-decorated microfiber, which is fabricated with a convenient and
      controllable evanescent-field-induced deposition method. Benefitting from the
      significantly enhanced light-graphene interaction of the subwavelength transvers
      dimension of the microfiber and accumulation of the saturable absorption of the
      piled graphene flakes, the microfiber shows nonlinear saturable absorption with a
      peak power threshold down to 1.75 W (60 MW/cm(2)), with a measured response time
      of about 3.5 ps.

PMID- 25969115
TI  - Bound constrained bundle adjustment for reliable 3D reconstruction.
AB  - Bundle adjustment (BA) is a common estimation algorithm that is widely used in
      machine vision as the last step in a feature-based three-dimensional (3D)
      reconstruction algorithm. BA is essentially a non-convex non-linear least-square
      problem that can simultaneously solve the 3D coordinates of all the feature
      points describing the scene geometry, as well as the parameters of the camera.
      The conventional BA takes a parameter either as a fixed value or as an
      unconstrained variable based on whether the parameter is known or not. In cases
      where the known parameters are inaccurate but constrained in a range,
      conventional BA results in an incorrect 3D reconstruction by using these
      parameters as fixed values. On the other hand, these inaccurate parameters can be
      treated as unknown variables, but this does not exploit the knowledge of the
      constraints, and the resulting reconstruction can be erroneous since the BA
      optimization halts at a dramatically incorrect local minimum due to its non
      convexity. In many practical 3D reconstruction applications, unknown variables
      with range constraints are usually available, such as a measurement with a range
      of uncertainty or a bounded estimate. Thus to better utilize these pre-known,
      constrained, but inaccurate parameters, a bound constrained bundle adjustment
      (BCBA) algorithm is proposed, developed and tested in this study. A scanning
      fiber endoscope (the camera) is used to capture a sequence of images above a
      surgery phantom (the object) of known geometry. 3D virtual models are
      reconstructed based on these images and then compared with the ground truth. The
      experimental results demonstrate BCBA can achieve a more reliable, rapid, and
      accurate 3D reconstruction than conventional bundle adjustment. 

PMID- 25969116
TI  - Dark counts of superconducting nanowire single-photon detector under
      illumination.
AB  - An abnormal increase in the SDE was observed for superconducting nanowire single
      photon detectors (SNSPDs) when the bias current (I(b)) was close to the switching
      current (I(sw)). By introducing the time-correlated single-photon counting
      technique, we investigated the temporal histogram of the detection counts of an
      SNSPD under illumination. The temporal information helps us to distinguish photon
      counts from dark counts in the time domain. In this manner, the dark count rate
      (DCR) under illumination and the accurate SDE can be determined. The DCR under
      moderate illumination may be significantly larger than the conventional DCR
      measured without illumination under a high I(b), which causes the abnormal
      increase in the SDE. The increased DCR may be explained by the suppression of
      I(sw) under illumination.

PMID- 25969117
TI  - Correction of phase extraction error in phase-shifting interferometry based on
      Lissajous figure and ellipse fitting technology.
AB  - The accuracy of phase-shifting interferometers (PSI) is crippled by nonlinearity
      of the phase shifter and instability of the environment such as vibration and air
      turbulence. A general algorithm, utilizing Lissajous figures and ellipse fitting,
      of correcting the phase extraction error in the phase shifting interferometry is
      described in this paper. By plotting N against D, where N and D represent the
      numerator and denominator terms of the phase extraction function (i.e. an
      arctangent function) respectively, a Lissajous ellipse is created. Once the
      parameters of the ellipse are determined by ellipse fitting, one can transform
      the ellipse to a unit circle (ETC). Through this process the phase extraction
      error caused by random phase shift errors can be corrected successfully. Proposed
      method is non-iterated, adapts to all phase shifting algorithms (PSAs), and has
      high accuracy. Some factors that may affect the performance of proposed method
      are discussed in numerical simulations. Optical experiments are implemented to
      validate the effectiveness of proposed algorithm. 

PMID- 25969119
TI  - Error analysis of single-snapshot full-Stokes division-of-aperture imaging
      polarimeters.
AB  - Single-snapshot full-Stokes imaging polarimetry is a powerful tool for the
      acquisition of the spatial polarization information in real time. According to
      the general linear model of a polarimeter, to recover full Stokes parameters at
      least four polarimetric intensities should be measured. In this paper, four types
      of single-snapshot full-Stokes division-of-aperture imaging polarimeter with four
      subapertures are presented and compared, with maximum spatial resolution for each
      polarimetric image on a single area-array detector. By using the error
      propagation theories for different incident states of polarization, the
      performance of four polarimeters are evaluated for several main sources of error,
      including retardance error, alignment error of retarders, and noise perturbation.
      The results show that the configuration of four 132 degrees  retarders with
      angular positions of ( +/- 51.7 degrees , +/- 15.1 degrees ) is an optimal choice
      for the configuration of four subaperture single-snapshot full-Stokes imaging
      polarimeter. The tolerance and uncertainty of this configuration are analyzed. 

PMID- 25969118
TI  - Effects of mixing states on the multiple-scattering properties of soot aerosols.
AB  - The radiative properties of soot aerosols are highly sensitive to the mixing
      states of black carbon particles and other aerosol components. Light absorption
      properties are enhanced by the mixing state of soot aerosols. Quantification of
      the effects of mixing states on the scattering properties of soot aerosol are
      still not completely resolved, especially for multiple-scattering properties.
      This study focuses on the effects of the mixing state on the multiple scattering
      of soot aerosols using the vector radiative transfer model. Two types of soot
      aerosols with different mixing states such as external mixture soot aerosols and
      internal mixture soot aerosols are studied. Upward radiance/polarization and
      hemispheric flux are studied with variable soot aerosol loadings for clear and
      haze scenarios. Our study showed dramatic changes in upward radiance/polarization
      due to the effects of the mixing state on the multiple scattering of soot
      aerosols. The relative difference in upward radiance due to the different mixing
      states can reach 16%, whereas the relative difference of upward polarization can
      reach 200%. The effects of the mixing state on the multiple-scattering properties
      of soot aerosols increase with increasing soot aerosol loading. The effects of
      the soot aerosol mixing state on upwelling hemispheric flux are much smaller than
      in upward radiance/polarization, which increase with increasing solar zenith
      angle. The relative difference in upwelling hemispheric flux due to the different
      soot aerosol mixing states can reach 18% when the solar zenith angle is 75
      degrees . The findings should improve our understanding of the effects of mixing
      states on the optical properties of soot aerosols and their effects on climate.
      The mixing mechanism of soot aerosols is of critical importance in evaluating the
      climate effects of soot aerosols, which should be explicitly included in
      radiative forcing models and aerosol remote sensing. 

PMID- 25969120
TI  - Generation and manipulation of ultrahigh order plasmon resonances in visible and
      near-infrared region.
AB  - Optical properties of periodic nanorings with built-in V-shaped nanowedges (NRBV)
      are investigated theoretically. Tunable ultrahigh order Fano resonances are
      achieved and they are found to be sensitive to geometric parameters and
      surrounding dielectric environment of the planar nanostructure. High order Fano
      resonances can be suppressed or enhanced by adjusting the opening angle of the
      nanowedge, the size of the nanoring and the aspect ratio of the nanowedge.
      Moreover, manipulating the offset of the built-in nanowedge, or filling
      dielectrics asymmetrically can revive suppressed Fano resonances when the V
      shaped nanowedge develops into a straight nanorod. Meanwhile, stronger plasmon
      resonances emerge alternately in the two parts of this planar nanostructure. This
      periodic plasmonic nanostructure produces ultrahigh order plasmon resonances and
      stronger electric field enhancement, which have great potential applications in
      multi-wavelength surface enhanced spectroscopy and biochemical sensing. 

PMID- 25969121
TI  - Integrated digital metamaterials enables ultra-compact optical diodes.
AB  - We applied nonlinear optimization to design integrated digital metamaterials in
      silicon for unidirectional energy flow. Two devices, one for each polarization
      state, were designed, fabricated, and characterized. Both devices offer
      comparable or higher transmission efficiencies and extinction ratios, are easier
      to fabricate, exhibit larger bandwidths and are more tolerant to fabrication
      errors, when compared to alternatives. Furthermore, each device footprint is only
      3MUm * 3MUm, which is the smallest optical diode ever reported. To illustrate the
      versatility of digital metamaterials, we also designed a polarization-independent
      optical diode. 

PMID- 25969122
TI  - Effects of transmission on Gaussian optical states.
AB  - The noise properties of phase-insensitive and phase-sensitive optical
      transmission links are described in detail, for Gaussian input signals. Formulas
      are derived for the quadrature covariance matrices of the output signals, which
      allow one to quantify the noise figures of the links and the fidelities of
      transmission. Another formula is derived, which relates the density operator of
      an output signal, in the number-state representation, to its covariance matrix.
      This density matrix allows one to quantify the decrease in coherence and changes
      in photon-number probabilities associated with transmission. Based on the
      aforementioned performance metrics, links with distributed phase-sensitive
      amplification perform significantly better than other links. 

PMID- 25969123
TI  - Target-site EPSPS Pro-106 mutations: sufficient to endow glyphosate resistance in
      polyploid Echinochloa colona?
AB  - BACKGROUND: This study confirms and characterises glyphosate resistance in two
      polyploid Echinochloa colona populations from north-eastern Australia. RESULTS:
      Glyphosate dose response revealed that the two resistant populations were
      marginally (up to twofold) resistant to glyphosate. Resistant plants did not
      differ in non-target-site foliar uptake and translocation of (14) C-glyphosate,
      but contained the known target-site 5-enolpyruvylshikimate-3-phosphate synthase
      (EPSPS) mutation Pro-106-Thr and/or Pro-106-Leu. Although plants carrying either
      a single or two EPSPS mutations were glyphosate resistant relative to the
      susceptible population, they were still controlled at the field rate of
      glyphosate (450 g a.e. ha(-1) ) when treated under warm conditions (25/20 
      degrees C). However, when treated in hot conditions (35/30  degrees C), most
      mutant resistant plants (68%) can survive the field rate, and an increase (2.5
      fold) in glyphosate LD50 was found for both the R and S populations. CONCLUSIONS:
      This study shows that one or two EPSPS Pro-106 mutations are insufficient to
      confer field-rate glyphosate resistance in polyploidy E. colona at mild
      temperatures. However, control of these mutant plants at the glyphosate field
      rate is poor at high temperatures, probably owing to reduced glyphosate efficacy.
      Therefore, glyphosate should be applied during relatively mild (warm) temperature
      periods in the summer growing season to improve E. colona control.

PMID- 25969125
TI  - B-type natriuretic peptide and heart failure: what can we learn from clinical
      trials?
AB  - The B-type natriuretic peptide (BNP) may favour natriuresis and diuresis, making
      it an ideal drug to aid in diuresing a fluid-overloaded patient with poor or
      worsening renal function. Several randomized clinical trials have tested the
      hypothesis that infusions of pharmacological doses of BNP to acute heart failure
      (HF) patients may enhance decongestion and preserve renal function in this
      clinical setting. Unfortunately, none of these has resulted in a better outcome.
      The current challenge for BNP research in acute HF lies in a failure of concept
      and reluctance to abandon a demonstrably ineffectual research model. Future
      success will necessitate a detailed understanding of the mechanism of action of
      BNP as well as a better integration of basic and clinical science.

PMID- 25969124
TI  - Voltage-gated sodium channels contribute to action potentials and spontaneous
      contractility in isolated human lymphatic vessels.
AB  - Voltage-gated sodium channels (VGSC) play a key role for initiating action
      potentials (AP) in excitable cells. VGSC in human lymphatic vessels have not been
      investigated. In the present study, we report the electrical activity and APs of
      small human lymphatic collecting vessels, as well as mRNA expression and function
      of VGSC in small and large human lymphatic vessels. The VGSC blocker TTX
      inhibited spontaneous contractions in six of 10 spontaneously active vessels,
      whereas ranolazine, which has a narrower VGSC blocking profile, had no influence
      on spontaneous activity. TTX did not affect noradrenaline-induced contractions.
      The VGSC opener veratridine induced contractions in a concentration-dependent
      manner (0.1-30 MUm) eliciting a stable tonic contraction and membrane
      depolarization to -18 +/- 0.6 mV. Veratridine-induced depolarizations and
      contractions were reversed ~80% by TTX, and were dependent on Ca(2+) influx via L
      type calcium channels and the sodium-calcium exchanger in reverse mode. Molecular
      analysis determined NaV 1.3 to be the predominantly expressed VGSC isoform.
      Electrophysiology of mesenteric lymphatics determined the resting membrane
      potential to be -45 +/- 1.7 mV. Spontaneous APs were preceded by a slow
      depolarization of 5.3 +/- 0.6 mV after which a spike was elicited that almost
      completely repolarized before immediately depolarizing again to plateau. Vessels
      transiently hyperpolarized prior to returning to the resting membrane potential.
      TTX application blocked APs. We have shown that VGSC are necessary for initiating
      and maintaining APs and spontaneous contractions in human lymphatic vessels and
      our data suggest the main contribution from comes NaV 1.3. We have also shown
      that activation of these channels augments the contractile activity of the
      vessels.

PMID- 25969126
TI  - Computing with synthetic protocells.
AB  - In this article we present a new kind of computing device that uses biochemical
      reactions networks as building blocks to implement logic gates. The architecture
      of a computing machine relies on these generic and composable building blocks,
      computation units, that can be used in multiple instances to perform complex
      boolean functions. Standard logical operations are implemented by biochemical
      networks, encapsulated and insulated within synthetic vesicles called protocells.
      These protocells are capable of exchanging energy and information with each other
      through transmembrane electron transfer. In the paradigm of computation we
      propose, protoputing, a machine can solve only one problem and therefore has to
      be built specifically. Thus, the programming phase in the standard computing
      paradigm is represented in our approach by the set of assembly instructions
      (specific attachments) that directs the wiring of the protocells that constitute
      the machine itself. To demonstrate the computing power of protocellular machines,
      we apply it to solve a NP-complete problem, known to be very demanding in
      computing power, the 3-SAT problem. We show how to program the assembly of a
      machine that can verify the satisfiability of a given boolean formula. Then we
      show how to use the massive parallelism of these machines to verify in less than
      20 min all the valuations of the input variables and output a fluorescent signal
      when the formula is satisfiable or no signal at all otherwise. 

PMID- 25969127
TI  - Bone Marrow-Derived Mesenchymal Stem Cells Have Innate Procoagulant Activity and
      Cause Microvascular Obstruction Following Intracoronary Delivery: Amelioration by
      Antithrombin Therapy.
AB  - Mesenchymal stem cells (MSCs) are currently under investigation as tools to
      preserve cardiac structure and function following acute myocardial infarction
      (AMI). However, concerns have emerged regarding safety of acute intracoronary
      (IC) MSC delivery. This study aimed to characterize innate prothrombotic activity
      of MSC and identify means of its mitigation toward safe and efficacious
      therapeutic IC MSC delivery post-AMI. Expression of the initiator of the
      coagulation cascade tissue factor (TF) on MSC was detected and quantified by
      immunofluorescence, FACS, and immunoblotting. MSC-derived TF antigen was
      catalytically active and capable of supporting thrombin generation in vitro.
      Addition of MSCs to whole citrated blood enhanced platelet thrombus deposition on
      collagen at arterial shear, an effect abolished by heparin coadministration. In a
      porcine AMI model, IC infusion of 25 * 10(6) MSC during reperfusion was
      associated with a decrease in coronary flow reserve but not when coadministered
      with an antithrombin agent (heparin). Heparin reduced MSC-associated thrombosis
      incorporating platelets and VWF within the microvasculature. Heparin-assisted
      therapeutic MSC delivery also reduced apoptosis in the infarct border zone at 24
      hours, significantly improved infarct size, left ventricular (LV) ejection
      fraction, LV volumes, wall motion, and attenuated histologic evidence of scar
      formation at 6 weeks post-AMI. Heparin alone or heparin-assisted fibroblast
      control cell delivery had no such effect. Procoagulant TF activity of therapeutic
      MSCs is associated with reductions in myocardial perfusion when delivered IC may
      be successfully managed by heparin coadministration. This study highlights an
      important mechanistic insight into safety concerns associated with therapeutic IC
      MSC delivery for AMI.

PMID- 25969128
TI  - Rethinking Meta-Analysis: Applications for Air Pollution Data and Beyond.
AB  - Meta-analyses offer a rigorous and transparent systematic framework for
      synthesizing data that can be used for a wide range of research areas, study
      designs, and data types. Both the outcome of meta-analyses and the meta-analysis
      process itself can yield useful insights for answering scientific questions and
      making policy decisions. Development of the National Ambient Air Quality
      Standards illustrates many potential applications of meta-analysis. These
      applications demonstrate the strengths and limitations of meta-analysis, issues
      that arise in various data realms, how meta-analysis design choices can influence
      interpretation of results, and how meta-analysis can be used to address bias and
      heterogeneity. Reviewing available data from a meta-analysis perspective can
      provide a useful framework and impetus for identifying and refining strategies
      for future research. Moreover, increased pervasiveness of a meta-analysis mindset
      focusing on how the pieces of the research puzzle fit together-would benefit
      scientific research and data syntheses regardless of whether or not a
      quantitative meta-analysis is undertaken. While an individual meta-analysis can
      only synthesize studies addressing the same research question, the results of
      separate meta-analyses can be combined to address a question encompassing
      multiple data types. This observation applies to any scientific or policy area
      where information from a variety of disciplines must be considered to address a
      broader research question. 

PMID- 25969129
TI  - Pleurodesis with povidone-iodine for refractory chylothorax in newborns: Personal
      experience and literature review.
AB  - INTRODUCTION: Refractory chylothorax is a severe clinical issue, particularly in
      neonates. Conventional primary approach is based on diet with medium-chain fatty
      acids and/or total parenteral nutrition. In nonresponders, proposed second line
      treatments include chemical or surgical pleurodesis, thoracic duct ligation,
      pleuroperitoneal shunting and pleurectomy but none of these have been shown to be
      superior to other in terms of resolution rate and safety. Our aim is to report
      our experience on povidone-iodine use for chemical pleurodesis in newborn infants
      with chylothorax unresponsive to conservative treatment. Our aim is to report our
      experience on povidone-iodine use for chemical pleurodesis in newborn infants
      with chylothorax unresponsive to conservative treatment. METHODS: Since 2013,
      povidone-iodine pleurodesis was attempted in all patients with persistent
      chylothorax who failed conservative treatment (no response to at least 10 days of
      total parenteral nutrition and maximum dosage of intravenous octreotide).
      Pleurodesis consisted in the injection of 2 ml/kg of a 4% povidone-iodine
      solution inside the pleural space, leaving the pleural tube clamped for the
      subsequent 4 hours. RESULTS: Five patients were treated with chemical pleurodesis
      of persistent chylothorax. Four of 5 patients had their pleural effusion treated
      by one single povidone-iodine infusion. Median time for resolution was 4 days. A
      patient with massive superior vena cava thrombosis did not benefit from
      pleurodesis. None of the patients experienced long term side effects of the
      treatment. CONCLUSION: Our data suggest that povidone-iodine pleurodesis may be
      considered a safe and effective option to treat refractory chylothorax in
      newborns.

PMID- 25969130
TI  - Phase II trial of everolimus in patients with refractory metastatic
      adenocarcinoma of the esophagus, gastroesophageal junction and stomach: possible
      role for predictive biomarkers.
AB  - PURPOSE: Our study was designed to evaluate the efficacy and safety of everolimus
      in patients with pre-treated metastatic gastric and esophagus cancers in a US
      based population focusing on biomarker correlation. METHODS: Patients with
      advanced upper GI adenocarcinomas who progressed after 1-2 prior regimens
      received everolimus 10 mg PO daily. The primary endpoint was disease control rate
      (DCR). Secondary endpoints included progression-free survival (PFS), toxicity,
      overall survival (OS) and biomarker correlatives of the mTOR pathway. Target
      accrual was 50 patients based on one-sided type I error of 10 % and power of 90
      %. RESULTS: Forty-five patients were evaluable, 21 gastric, 11 esophagus and 13
      from the GEJ. The median age was 64 (range 38-73); all patients had an ECOG of 0
      or 1; and 18 patients (40 %) had only 1 prior regimen. The most common grade 3-4
      adverse events included fatigue (24 %) and thrombocytopenia (22 %). We observed 1
      partial response with 39 % of evaluable patients having stable disease. Median OS
      was 3.4 months (95 % CI 2.7-5.6 months), and PFS was 1.8 months (95 % CI 1.7-2.2
      months). There was a strong correlation between >=2 + IHC staining for p-S6 in
      tumor samples with better PFS (p < 0.0001) and DCR (p = 0.0001). CONCLUSIONS: Our
      clinical outcomes were inferior to the Asian studies, which may be explained by
      disease heterogeneity. However, there was a similar strong correlation between
      clinical benefit and tumor high pS6. Testing this biomarker in patient samples
      from the randomized phase III Granite trial may lead to a positive predictive
      marker.

PMID- 25969131
TI  - Review of the Mechanism of Tooth Whitening.
AB  - PURPOSE: This review integrated the current literature on diffusion of whitening
      agents, their interactions with stain molecules, and changes to the surface, with
      the aim of establishing a better understanding of the mechanism underlying tooth
      whitening. MATERIALS AND METHODS: An electronic PubMed database search, with
      combinations of the following terms was performed: Tooth Bleaching, Tooth
      Bleaching Agent, Hydrogen Peroxide, Pharmacokinetics, Tooth Permeability,
      Oxidation-Reduction, Tooth Demineralization, and Color. RESULTS: Tooth whitening
      is a dynamic process that involves diffusion of the whitening material to
      interact with stain molecules and also involves micromorphologic alterations on
      the surface and changes within the tooth that affect its optical properties. The
      interaction seems not to be limited to stain molecules, but rather an affinity
      based interaction process that also accompanies effects on sound enamel and
      dentin structures. CONCLUSIONS: This review underlines that supervision by dental
      health professionals as recommended by the American Dental Association (ADA)
      Council on Scientific Affairs is critical to achieving a successful and safe
      whitening outcome. CLINICAL SIGNIFICANCE: The mechanism that underlies tooth
      whitening with the use of peroxide-based materials is a complex phenomenon
      encompassing diffusion, interaction, and surfaces changes within the tooth.
      Therefore, supervision by dental health professionals as recommended by the ADA
      Council on Scientific Affairs is imperative to achieve a successful and safe
      whitening outcome.

PMID- 25969132
TI  - Rare cancers in The Netherlands: a population-based study.
AB  - The conventional definition for rare disease is based on prevalence. Because of
      differences in prognosis, a definition on the basis of incidence was deemed to be
      more appropriate for rare cancers. Within the European RARECARE project, a
      definition was introduced that defines cancers as rare when the crude incidence
      rate is less than six per 100 000 per year. In this study, we applied the
      RARECARE definition for rare cancer to the Netherlands; this to identify the
      usefulness of the definition in a single country and to provide more insight into
      the burden of rare cancers in the Netherlands. Data for 2004 through 2008 were
      extracted from the Netherlands Cancer Registry and classified according to the
      RARECARE entities (tumour groupings). Crude and European standardized incidence
      rates were calculated. Out of the 260 entities, 223 (86%) were rare according to
      the definition, accounting for 14 000 cancers (17% of all). Considerable
      fluctuations in crude rates over years were observed for the major group of
      cancers. Rare tumours in the Netherlands constituted 17% of all newly diagnosed
      tumours, but were divided over 223 different entities, indicating the challenge
      that faces clinicians. To make the definition of rare cancers better applicable,
      it should be refined by taking into consideration the sex-specific incidence for
      sex-specific cancer sites. Moreover, a mean incidence over 5 years will provide
      more solid insight into the burden, eliminating large fluctuations in time of
      most of the cancers.

PMID- 25969133
TI  - The Risk of End-Stage Renal Disease Among Living Donor Liver Transplant
      Recipients in the United States.
AB  - Since initiation of model for end-stage liver disease (MELD)-based allocation for
      liver transplantation, the risk of posttransplant end-stage renal disease (ESRD)
      has increased. Recent US data have demonstrated comparable, if not superior
      survival, among recipients of living donor liver transplants (LDLT) when compared
      to deceased donor liver transplant (DDLT) recipients. However, little is known
      about the incidence of ESRD post-LDLT. We analyzed linked Scientific Registry of
      Transplant Recipients (SRTR) and US Renal Data System (USRDS) data of first-time
      liver-alone transplant recipients from February 27, 2002 to March 1, 2011, and
      restricted the cohort to recipients with a laboratory MELD score <=25 not on
      dialysis prior to transplantation, in order to evaluate the incidence of ESRD
      post-LDLT, and to compare the incidence among LDLT versus DDLT recipients. There
      were 28 707 DDLT and 1917 LDLT recipients included in the analyses. The 1-, 3-
      and 5-year unadjusted risk of ESRD was 1.7%, 2.9% and 3.4% in LDLT recipients,
      compared with 1.5%, 3.0% and 4.8% in DDLT recipients (p > 0.05), respectively. In
      multivariable competing risk Cox regression models, there was no association
      between receiving an LDLT and risk of ESRD (sub-hazard ratio: 0.99, 95% CI: 0.77
      1.26, p = 0.92). In conclusion, the incidence of ESRD post-LDLT in the United
      States is low, and there are no significant differences among LDLT and DDLT
      recipients with MELD scores <=25 at transplantation.

PMID- 25969134
TI  - Par-4 dependent modulation of cellular beta-catenin by medicinal plant natural
      product derivative 3-azido Withaferin A.
AB  - Here, we provide evidences that natural product derivative 3-azido Withaferin A
      (3-AWA) abrogated EMT and invasion by modulating beta-catenin localization and
      its transcriptional activity in the prostate as well as in breast cancer cells.
      This study, for the first time, reveals 3-AWA treatment consistently sequestered
      nuclear beta-catenin and augmented its cytoplasmic pool as evidenced by reducing
      beta-catenin transcriptional activity in these cells. Moreover, 3-AWA treatment
      triggered robust induction of pro-apoptotic intracellular Par-4, attenuated Akt
      activity and rescued Phospho-GSK3beta (by Akt) to promote beta-catenin
      destabilization. Further, our in vitro studies demonstrate that 3-AWA treatment
      amplified E-cadherin expression along with sharp downregulation of c-Myc and
      cyclin D1 proteins. Strikingly, endogenous Par-4 knock down by siRNA underscored
      3-AWA mediated inhibition of nuclear beta-catenin was Par-4 dependent and
      suppression of Par-4 activity, either by Bcl-2 or by Ras transfection, restored
      the nuclear beta-catenin level suggesting Par-4 mediated beta-catenin regulation
      was not promiscuous. In vivo results further demonstrated that 3-AWA was
      effective inhibitor of tumor growth and immunohistochemical studies indicated
      that increased expression of total beta-catenin and decreased expression of
      phospho-beta-catenin and Par-4 in breast cancer tissues as compared to normal
      breast tissue suggesting Par-4 and beta-catenin proteins are mutually regulated
      and inversely co-related in normal as well as cancer condition. Thus, strategic
      regulation of intracellular Par-4 by 3-AWA in diverse cancers could be an
      effective tool to control cancer cell metastasis. Conclusively, this report puts
      forward a novel approach of controlling deregulated beta-catenin signaling by 3
      AWA induced Par-4 protein.

PMID- 25969135
TI  - Arabidopsis abscisic acid receptors play an important role in disease resistance.
AB  - Stomata are natural pores of plants and constitute the entry points for water
      during transpiration. However, they also facilitate the ingress of potentially
      harmful bacterial pathogens. The phytohormone abscisic acid (ABA) plays a pivotal
      role in protecting plants against biotic stress, by regulating stomatal closure.
      In the present study, we investigated the mechanism whereby ABA influences plant
      defense responses to Pseudomonas syringae pv. tomato (Pst) DC3000, which is a
      virulent bacterial pathogen of Arabidopsis, at the pre-invasive stage. We found
      that overexpression of two ABA receptors, namely, RCAR4/PYL10-OX and RCAR5/PYL11
      OX (hereafter referred to as RCARs), resulted in ABA-hypersensitive phenotypes
      being exhibited during the seed germination and seedling growth stages.
      Sensitivity to ABA enhanced the resistance of RCAR4-OX and RCAR5-OX plants to Pst
      DC3000, through promoting stomatal closure leading to the development of
      resistance to this bacterial pathogen. Protein phosphatase HAB1 is an important
      component that is responsible for ABA signaling and which interacts with ABA
      receptors. We found that hab1 mutants exhibited enhanced resistance to Pst
      DC3000; moreover, similar to RCAR4-OX and RCAR5-OX plants, this enhanced
      resistance was correlated with stomatal closure. Taken together, our findings
      demonstrate that alteration of RCAR4- or RCAR5-HAB1 mediated ABA signaling
      influences resistance to bacterial pathogens via stomatal regulation. 

PMID- 25969136
TI  - Characteristics of patients patch tested in the European Surveillance System on
      Contact Allergies (ESSCA) network, 2009-2012.
AB  - BACKGROUND: Patch test results often vary between departments, and also between
      countries. Such variation may be partly attributable to systematic effects
      introduced by patient characteristics, differing exposures, patient selection, or
      methodological differences. OBJECTIVE: To examine the amount of variation of
      patient characteristics in terms of the MOAHLFA index and of the proportion of
      patients with at least one positive reaction to the (European) baseline series
      ('P' measure), and to examine potential reasons for the variation. METHODS: A
      retrospective analysis was performed of patch test data from 63 530 consultations
      collected by 53 departments from 12 countries participating in the European
      Surveillance System on Contact Allergies (ESSCA) ( www.essca-dc.org) between 2009
      and 2012. RESULTS: Considerable variation in the prevalence of the MOAHLFA
      factors between departments was found, caused, for example, by differing
      specializations (e.g. occupational dermatology) or patient characteristics.
      Notable variation concerning the 'P' measure was observed; however, larger
      national networks (contributing to the ESSCA) tend to have quite similar ranges
      of this measure. CONCLUSIONS: Data from one department per country give valuable
      insights into the spectrum of contact allergy prevalence rates in that country,
      but are not as representative as national data pooled from several departments.

PMID- 25969137
TI  - Genotypic and phenotypic virulence characteristics and antimicrobial resistance
      of Yersinia spp. isolated from meat and milk products.
AB  - A total of 300 food samples including 180 milk and 120 meat products have been
      examined for the presence of Yersinia spp. using the ISO 10273 and the cold
      enrichment method. The overall prevalence of Yersinia spp. was 84 (28%). Yersinia
      enterocolitica was isolated from 18 (6%) of the 300 samples. The other Yersinia
      species were detected in the samples Yersinia rohdei 15 (5%), Yersinia intermedia
      14 (4.7%), Yersinia pseudotuberculosis 12 (4%), Yersinia ruckeri 12 (4%),
      Yersinia mollaretii 5 (1.7%), Yersinia bercovieri 4 (1.3%), and atypical Yersinia
      spp. 4 (1.3%). The conventionally identified Y. enterocolitica strains were also
      confirmed by the 16S rRNA gene sequencing. All Y. enterocolitica strains biotyped
      as 1A had negative results in the phenotypic virulence tests. The 84 Yersinia
      strains were also examined genotypically for the presence of virulence genes.
      None of the Y. enterocolitica and other Yersinia strains contained the ail, ystA,
      yadA, and virF except only 1 Y. intermedia and 2 Y. enterocolitica strains that
      were found to be positive for ystB. Antimicrobial resistance of 84 Yersinia to 16
      antimicrobial agents was determined by the disk diffusion method. All strains
      were sensitive to tobramycine and imipenem while resistant to clindamycin.
      Although 84.5% of the strains were resistant to at least 3 or more antimicrobial
      agents, 64.3% of them were resistant to 4 or more antimicrobial agents. 

PMID- 25969138
TI  - Postimplantation changes of electrophysiological parameters in patients with
      cochlear implants.
AB  - OBJECTIVE: To evaluate the postoperative changes of the basic
      electrophysiological and psychophysical parameters in cochlear implant (CI)
      patients: the impedance of the electrode contacts, the electrically-evoked
      compound action potential (ECAP) thresholds and the T/C levels. STUDY DESIGN AND
      SETTING: Retrospective case review in a quaternary otologic referral centre.
      MATERIALS AND METHODS: Data on the impedance of the electrode contacts, the ECAP
      thresholds and the T/C levels were collected in 20 consecutive CI patients
      divided into 2 groups. Group 1 comprised 10 prelingually deaf children implanted
      before the age of 18 months, and group 2 comprised 10 postlingually deaf adults
      (average age of 58 years). All patients were users of the Nucleus 24RECA
      (Freedom, Contour advance off-stylet electrode) CI. RESULTS AND CONCLUSIONS: (1)
      The mid-portion and the apical electrodes showed a decrease in the impedance
      values between the 1st and the 6th postoperative months and stabilization in the
      later course. Impedance of the most basal electrodes grew during the first
      postoperative months and stabilized later on, but remained higher than the
      impedance of the mid-portion and the apical electrodes. (2) The neural response
      telemetry threshold values tended to decrease within the first 3 months after
      surgery to reach a plateau afterwards. (3) The behavioural threshold levels
      remained generally stable, except for the basal electrodes where a decrease could
      be observed. The hearing comfort levels showed an increase during the first 6
      months of the implant use and remained stable afterwards.

PMID- 25969139
TI  - Melatonin reduces the need for sedation in ICU patients: a randomized controlled
      trial.
AB  - BACKGROUND: Critically ill patients suffer from physiological sleep deprivation
      and have reduced blood melatonin levels. This study was designed to determine
      whether nocturnal melatonin supplementation would reduce the need for sedation in
      patients with critical illness. METHODS: A single-center, double-blind randomized
      placebo-controlled trial was carried out from July 2007 to December 2009, in a
      mixed medical-surgical Intensive Care Unit of a University hospital, without any
      form of external funding. Of 1158 patients admitted to ICU and treated with
      conscious enteral sedation, 82 critically-ill with mechanical ventilation >48
      hours and Simplified Acute Physiology Score II>32 points were randomized 1:1 to
      receive, at eight p.m. and midnight, melatonin (3+3mg) or placebo, from the third
      ICU day until ICU discharge. Primary outcome was total amount of enteral
      hydroxyzine administered. RESULTS: Melatonin treated patients received lower
      amount of enteral hydroxyzine. Other neurological indicators (amount of some
      neuroactive drugs, pain, agitation, anxiety, sleep observed by nurses, need for
      restraints, need for extra sedation, nurse evaluation of sedation adequacy)
      seemed improved, with reduced cost for neuroactive drugs. Post-traumatic stress
      disorder prevalence did not differ between groups, nor did ICU or hospital
      mortality. Study limitations include the differences between groups before
      intervention, the small sample size, and the single-center observation.
      CONCLUSION: Long-term enteral melatonin supplementation may result in a decreased
      need for sedation, with improved neurological indicators and cost reduction.
      Further multicenter evaluations are required to confirm these results with
      different sedation protocols.

PMID- 25969140
TI  - Immunonutrients in critically ill patients: an analysis of the most recent
      literature.
AB  - Modulation of inflammatory and immune response to critical illness has been the
      goal of much research in the last decade and a variety of drugs and nutrients (so
      called "immunonutrients") have been tested in experimental models with promising
      results. Though, in the clinical setting of intensive care, their efficacy have
      been inconsistently proven, most likely because the effects of each drug may vary
      in relation to the timing, the dose, the route of administration, the interaction
      with other nutrients, the severity of illness and many other factors. Though the
      early studies of the beginning of this century (2000-2009) have shown some
      clinical benefits, recent multicenter trials (2011-2015) have failed to prove a
      consistent benefit of immunonutrition in terms of mortality or other clinical
      endpoints. Reviewing the latest evidence-based documents on this subject
      (multicenter trials, systematic reviews, meta-analyses and international
      guidelines), there is no convincing evidence that immunonutrients may be
      beneficial in the critically ill. Considering that these substances invariably
      increase the costs of health care and may be unsafe or even harmful in some
      subgroups, particularly in septic patients, we conclude that routine
      administration of immune-nutrients (glutamine, arginine, omega-3 fatty acids,
      selenium, etc.) cannot be currently recommended in the critically ill. 

PMID- 25969141
TI  - The joint effect of mesoscale and microscale roughness on perceived gloss.
AB  - Computer simulated stimuli can provide a flexible method for creating artificial
      scenes in the study of visual perception of material surface properties. Previous
      work based on this approach reported that the properties of surface roughness and
      glossiness are mutually interdependent and therefore, perception of one affects
      the perception of the other. In this case roughness was limited to a surface
      property termed bumpiness. This paper reports a study into how perceived gloss
      varies with two model parameters related to surface roughness in computer
      simulations: the mesoscale roughness parameter in a surface geometry model and
      the microscale roughness parameter in a surface reflectance model. We used a real
      world environment map to provide complex illumination and a physically-based path
      tracer for rendering the stimuli. Eight observers took part in a 2AFC experiment,
      and the results were tested against conjoint measurement models. We found that
      although both of the above roughness parameters significantly affect perceived
      gloss, the additive model does not adequately describe their mutually interactive
      and nonlinear influence, which is at variance with previous findings. We
      investigated five image properties used to quantify specular highlights, and
      found that perceived gloss is well predicted using a linear model. Our findings
      provide computational support to the 'statistical appearance models' proposed
      recently for material perception. 

PMID- 25969143
TI  - Hepatic inflammation facilitates transcription-associated mutagenesis via AID
      activity and enhances liver tumorigenesis.
AB  - Chronic inflammation triggers the aberrant expression of a DNA mutator enzyme,
      activation-induced cytidine deaminase (AID), and contributes to tumorigenesis
      through the accumulation of genetic aberrations. To gain further insight into the
      inflammation-mediated genotoxic events required for carcinogenesis, we examined
      the role of chronic inflammation in the emergence of genetic aberrations in the
      liver with constitutive AID expression. Treatment with thioacetamide (TAA) at low
      dose concentrations caused minimal hepatic inflammation in both wild-type (WT)
      and AID transgenic (Tg) mice. None of the WT mice with low-dose TAA
      administration or AID Tg mice without hepatic inflammation developed cancers in
      their liver tissues over the 6 month study period. In contrast, all the AID Tg
      mice with TAA treatment developed multiple macroscopic hepatocellular carcinomas
      during the same observation period. Whole exome sequencing and additional deep
      sequencing analyses revealed the enhanced accumulation of somatic mutations in
      various genes, including dual specificity phosphatase 6 (Dusp6), early growth
      response 1 (Egr1) and inhibitor of DNA binding 2 (Id2), which are putative tumor
      suppressors, in AID-expressing liver with TAA-mediated hepatic inflammation.
      Microarray and quantitative reverse transcription-polymerase chain reaction
      analyses showed the transcriptional upregulation of various genes including
      Dusp6, Egr1 and Id2 under hepatic inflammatory conditions. Together, these
      findings suggest that inflammation-mediated transcriptional upregulation of
      target genes, including putative tumor suppressor genes, enhances the opportunity
      for inflamed cells to acquire somatic mutations and contributes to the
      acceleration of tumorigenesis in the inflamed liver tissues. 

PMID- 25969142
TI  - Survival of skin cancer stem cells requires the Ezh2 polycomb group protein.
AB  - Polycomb group proteins, including Ezh2, are important candidate stem cell
      maintenance proteins in epidermal squamous cell carcinoma. We previously showed
      that epidermal cancer stem cells (ECS cells) represent a minority of cells in
      tumors, are highly enriched in Ezh2 and drive aggressive tumor formation. We now
      show that Ezh2 is required for ECS cell survival, migration, invasion and tumor
      formation and that this is associated with increased histone H3 trimethylation on
      lysine 27, a mark of Ezh2 action. We also show that Ezh2 knockdown or treatment
      with Ezh2 inhibitors, GSK126 or EPZ-6438, reduces Ezh2 level and activity,
      leading to reduced ECS cell spheroid formation, migration, invasion and tumor
      growth. These studies indicate that epidermal squamous cell carcinoma cells
      contain a subpopulation of cancer stem (tumor-initiating) cells that are enriched
      in Ezh2, that Ezh2 is required for optimal ECS cell survival and tumor formation
      and that treatment with Ezh2 inhibitors may be a strategy for reducing ECS cell
      survival and suppressing tumor formation.

PMID- 25969144
TI  - miR-145 suppress the androgen receptor in prostate cancer cells and correlates to
      prostate cancer prognosis.
AB  - Androgen signalling through the androgen receptor (AR) is essential for prostate
      cancer initiation, progression and transformation to the lethal castration
      resistant state. The aim of this study was to characterize the mechanisms by
      which miR-145 deregulation contribute to prostate cancer progression. The miR-145
      levels, measured by quantitative reverse transcription-polymerase chain reaction,
      were found to inversely correlate with occurrence of metastases, survival and
      androgen deprivation therapy response in a well-characterized prostate cancer
      cohort. Introduction of ectopic miR-145 in prostate cancer cells generated an
      inhibitory effect on the AR at both transcript and protein levels as well as its
      activity and downstream targets prostate-specific antigen (PSA), kallikrein
      related peptidase 2 and TMPRSS2. The regulation was shown to be mediated by
      direct binding using Ago2-specific immunoprecipitation, but there was also
      indication of synergetic AR activation. These findings were verified in clinical
      prostate specimens by demonstrating inverse correlations between miR-145 and AR
      expression as well as serum PSA levels. In addition, miR-145 was found to
      regulate androgen-dependent cell growth in vitro. Our findings put forward novel
      possibilities of therapeutic intervention, as miR-145 potentially could decrease
      both the stem cells and the AR expressing bulk of the tumour and hence reduce the
      transformation to the deadly castration-resistant form of prostate cancer. 

PMID- 25969145
TI  - Alpha EEG Frontal Asymmetries during Audiovisual Perception in Cochlear Implant
      Users. A Study with Bilateral and Unilateral Young Users.
AB  - OBJECTIVES: The aim of the present study is to investigate the variations of the
      electroencephalographic (EEG) alpha rhythm in order to measure the appreciation
      of bilateral and unilateral young cochlear implant users during the observation
      of a musical cartoon. The cartoon has been modified for the generation of three
      experimental conditions: one with the original audio, another one with a
      distorted sound and, finally, a mute version. METHODS: The EEG data have been
      recorded during the observation of the cartoons in the three experimental
      conditions. The frontal alpha EEG imbalance has been calculated as a measure of
      motivation and pleasantness to be compared across experimental populations and
      conditions. RESULTS: The EEG frontal imbalance of the alpha rhythm showed
      significant variations during the perception of the different cartoons. In
      particular, the pattern of activation of normal-hearing children is very similar
      to the one elicited by the bilateral implanted patients. On the other hand,
      results related to the unilateral subjects do not present significant variations
      of the imbalance index across the three cartoons. CONCLUSION: The presented
      results suggest that the unilateral patients could not appreciate the difference
      in the audio format as well as bilaterally implanted and normal hearing subjects.
      The frontal alpha EEG imbalance is a useful tool to detect the differences in the
      appreciation of audiovisual stimuli in cochlear implant patients.

PMID- 25969146
TI  - A Nonaromatic thiophene-fused heptalene and its aromatic dianion.
AB  - Heptalene, a nonaromatic, bicyclic 12 pi-electron system with a twisted
      structure, is of great interest with regard to its potential Huckel aromaticity
      in the two-electron oxidized or reduced forms. The synthesis of thiophene-fused
      heptalene 5 from the reductive transannular cyclization of bisdehydro[12]annulene
      4, and its solid-state structure, which was confirmed by X-ray crystallographic
      analysis, is presented. Chemical reduction of 5 readily generated the
      corresponding dianion, which was successfully isolated as [(K[2.2.2]cryptand)(+)
      ]2 5(2-) . The X-ray crystallographic analysis of the dianion revealed a
      shallower saddle structure for the heptalene moiety and a lesser degree of bond
      alternation relative to 5. (1) H NMR spectroscopy exposed the effect of a
      diamagnetic ring current on dianion 5(2-) , which was corroborated by nucleus
      independent chemical shift (NICS) calculations. These results demonstrate that
      the heptalene dianion, containing 14 pi-electrons, does indeed exhibit pronounced
      degrees of Huckel aromaticity. 

PMID- 25969147
TI  - Introduction: clinical ethics beyond the urban hospital.

PMID- 25969148
TI  - A real-space stochastic density matrix approach for density functional electronic
      structure.
AB  - The recent development of real-space grid methods has led to more efficient,
      accurate, and adaptable approaches for large-scale electrostatics and density
      functional electronic structure modeling. With the incorporation of multiscale
      techniques, linear-scaling real-space solvers are possible for density functional
      problems if localized orbitals are used to represent the Kohn-Sham energy
      functional. These methods still suffer from high computational and storage
      overheads, however, due to extensive matrix operations related to the underlying
      wave function grid representation. In this paper, an alternative stochastic
      method is outlined that aims to solve directly for the one-electron density
      matrix in real space. In order to illustrate aspects of the method, model
      calculations are performed for simple one-dimensional problems that display some
      features of the more general problem, such as spatial nodes in the density
      matrix. This orbital-free approach may prove helpful considering a future
      involving increasingly parallel computing architectures. Its primary advantage is
      the near-locality of the random walks, allowing for simultaneous updates of the
      density matrix in different regions of space partitioned across the processors.
      In addition, it allows for testing and enforcement of the particle number and
      idempotency constraints through stabilization of a Feynman-Kac functional
      integral as opposed to the extensive matrix operations in traditional approaches.

PMID- 25969149
TI  - 22nd European Congress on Obesity (ECO2015), Prague, Czech Republic, May 6-9,
      2015: Abstracts.

PMID- 25969150
TI  - A 12-Year Experience With Chimney and Periscope Grafts for Treatment of Type I
      Endoleaks.
AB  - PURPOSE: To evaluate the midterm outcomes of chimney and/or periscope grafts
      (CPGs) in patients presenting type I endoleak after a previous endovascular
      aneurysm repair (EVAR). METHODS: Between June 2002 and April 2014, 24 consecutive
      patients (mean age 73.9+/-9.2 years; 23 men) presenting a type I endoleak were
      addressed with CPGs to extend the proximal and/or distal landing zone and to
      maintain side branch perfusion. Indication for treatment was a type Ia endoleak
      in 23 (96%) patients and a type Ib endoleak in one. Median interval from the
      previous EVAR to endoleak treatment with CPGs was 52.2+/-48.9 months (range 0.2
      179). All patients had proximal/distal landing zones precluding any standard
      endovascular reintervention. Measured outcomes included technical success and
      perioperative mortality and morbidity. Technical success was defined as a
      procedure completed as intended, with no secondary procedures within 30 days.
      Midterm outcomes included survival, CPG patency, endoleaks, and freedom from
      reintervention. RESULTS: Technical success was 96%; a single patient required an
      additional procedure to seal a recurrent type Ia endoleak. Intraoperative
      revascularization of all 55 target vessels (2.3/patient) with CPGs was
      successful. One (4%) patient died within 30 days. Estimated survival at 12, 24,
      and 36 months was 83%; estimated CPG patency at the same intervals was 94%. Over
      a mean follow-up of 23.4+/-29 months, 6 (25%) reinterventions were performed; of
      these, 4 were secondary to type I endoleak. Aneurysm diameters reduced from
      88.3+/-26 to 85.5+/-33 mm (p=0.49) over the mean follow-up. CONCLUSION: The CPG
      technique is a safe and effective tool for treatment of type I endoleak after
      previous EVAR. The CPG technique is feasible even in nonelective patients, with
      excellent outcomes in terms of patency. Close imaging follow-up is warranted to
      rule out recurrent or de novo endoleaks.

PMID- 25969151
TI  - Water-soluble chiral metallopeptoids.
AB  - Metal ions play a significant role in the activity of biological systems
      including catalysis, recognition and folding. Therefore, introducing metal ions
      into peptidomimetic oligomers is a potential way for creating biomimetic metal
      complexes toward applications in sensing, recognition, drug design and catalysis.
      Herein we report the design, synthesis and characterization of water-soluble
      chiral N-substituted glycine oligomers, "peptoids," with one and two distinct
      intramolecular binding sites for metal ions such as copper and cobalt. We
      demonstrate for the first time the incorporation of the chiral hydrophilic group
      (S)-(+)-1-methoxy-2-propylamine (Nsmp) within peptoid sequences, which provides
      both chirality and water solubility. Two peptoids, a heptamer, and a dodecamer
      bearing two and four 8-hydroxyquinoline (HQ) groups respectively as metal-binding
      ligands, were synthesized on solid support using the submonomer approach. Using
      UV-titrations and ESI-MS analysis we demonstrate the creation of a novel
      metallopeptoid bearing two metal ions in distinct binding sites via
      intramolecular chelation. Exciton couplet circular dichroism (ECCD) demonstrated
      chiral induction from the chiral non-helical peptoids to the metal centers.

PMID- 25969152
TI  - A Systematic Review of the Economic and Humanistic Burden of Gout.
AB  - BACKGROUND: Gout is a chronic and inflammatory form of arthritis that is often
      overlooked despite the associated pain caused by acute flares and associated
      joint damage caused by the development of debilitating tophi. The increasing
      burden of gout, due to an aging population and the increased prevalence of known
      risk factors for hyperuricaemia, means that there is a continued need for new and
      effective urate-lowering treatments. The evaluation of these treatments will
      require a comprehensive and comparative evidence base describing the economic and
      humanistic burden of gout, taken from the perspective of patients, the healthcare
      system, and wider society. OBJECTIVE: The objective of this study is to review
      and summarise the current evidence of the disease burden related to chronic gout,
      assessed in terms of both cost and health-related quality of life (HRQL), and to
      identify key factors correlated with an increased burden. The overall aim is to
      support the economic evaluation of new treatments for gout, and to highlight key
      data gaps that may need further study and exploration. METHODS: Relevant
      literature dating from January 2000 to July 2014 was sourced through searches of
      the MEDLINE database via PubMed and The Cochrane Library. Articles published in
      English and reporting either the economic burden (cost) or the humanistic burden
      (HRQL/utility) of gout were identified, and key data were extracted and
      summarised, with key themes and data gaps identified and discussed. RESULTS: Of
      the 323 studies identified, 39 met the inclusion criteria, of which 17 and 26
      were relevant to the economic and humanistic burden, respectively. The economic
      burden of gout varied according to numerous factors, most notably serum urate
      acid levels and number of flares and tophi, resulting in higher healthcare
      resource use most often attributed to hospitalisation and inpatient stay. The
      incremental direct cost of gout has been suggested in the range of US$3165 to
      US$5515 (2004 and 2005 values, respectively) climbing to US$10,222 to US$21,467
      (2008 values) per annum where patients are experiencing regular acute flares and
      have tophi present. The humanistic burden of gout was largely due to physical
      disability and pain resulting from chronic clinical manifestations. Short Form 6
      dimensions (SF-6D) assessed utility weights are estimated at 0.53 for a patient
      with severe gout (>=3 flares/year and tophi) compared with 0.73 for an
      asymptomatic gout patient with serum acid levels <6 mg/dl. CONCLUSIONS: The
      evidence confirms that gout has a growing overall prevalence and represents a
      significant burden in terms of both direct healthcare cost and HRQL outcomes. In
      light of this, effective urate-lowering treatments are likely to be valued if
      they can be clearly demonstrated to be both clinically effective and cost
      effective. Published data to support healthcare decision making in non-US
      countries with regards to treatments for gout are currently limited, which is a
      key limitation of the current evidence base. More research is also required to
      extend our understanding of the impact of gout on indirect costs, and a need also
      exists to develop a more comprehensive set of comparative HRQL utility
      assessments.

PMID- 25969153
TI  - Interaction between Erythrocyte Phospholipid Fatty Acids Composition and Variants
      of Inflammation-Related Genes on Type 2 Diabetes.
AB  - AIMS: The present study aimed to investigate the interaction between erythrocyte
      phospholipid (PL) fatty acids and variants of inflammation-related genes in a
      Chinese population. METHODS: A total of 622 patients with type 2 diabetes
      mellitus (T2DM) and 293 healthy subjects were included. Determination of
      erythrocyte PL fatty acids composition and genotyping of single nucleotide
      polymorphisms were conducted by standard methods. RESULTS: A significant
      interaction of rs7305618 on HNFIA with C18:2n-6 and C20:4n-6 was observed: T
      allele carriers (TT+CT) had a higher risk of T2DM than noncarriers only when they
      had a higher level of C18:2n-6 or C20:4n-6, and the odds ratios (ORs) were 2.59
      (95% CI 1.58-4.24; p for interaction=0.005) and 2.49 (95% CI 1.47-4.24; p for
      interaction=0.021), respectively. A significant interaction of rs8078723 at the
      intergenic region between PSMD3 and CSF3 with C20:5n-3 was observed: C allele
      carriers (CC+CT) had a lower risk of T2DM than noncarriers only when they had a
      higher level of C20:5n-3, and the OR was 0.44 (95% CI 0.26-0.73; p for
      interaction=0.014). CONCLUSIONS: rs7305618 and rs8078723 were associated with the
      risk of T2DM in a Chinese population and were modulated by erythrocyte PL fatty
      acids composition.

PMID- 25969154
TI  - CD24+ Ovarian Cancer Cells Are Enriched for Cancer-Initiating Cells and Dependent
      on JAK2 Signaling for Growth and Metastasis.
AB  - Ovarian cancer is known to be composed of distinct populations of cancer cells,
      some of which demonstrate increased capacity for cancer initiation and/or
      metastasis. The study of human cancer cell populations is difficult due to long
      requirements for tumor growth, interpatient variability, and the need for tumor
      growth in immune-deficient mice. We therefore characterized the cancer initiation
      capacity of distinct cancer cell populations in a transgenic murine model of
      ovarian cancer. In this model, conditional deletion of Apc, Pten, and Trp53 in
      the ovarian surface epithelium (OSE) results in the generation of high-grade
      metastatic ovarian carcinomas. Cell lines derived from these murine tumors
      express numerous putative stem cell markers, including CD24, CD44, CD90, CD117,
      CD133, and ALDH. We show that CD24(+) and CD133(+) cells have increased tumor
      sphere-forming capacity. CD133(+) cells demonstrated a trend for increased tumor
      initiation while CD24(+) cells versus CD24(-) cells had significantly greater
      tumor initiation and tumor growth capacity. No preferential tumor-initiating or
      growth capacity was observed for CD44(+), CD90(+), CD117(+), or ALDH(+) versus
      their negative counterparts. We have found that CD24(+) cells, compared with
      CD24(-) cells, have increased phosphorylation of STAT3 and increased expression
      of STAT3 target Nanog and c-myc. JAK2 inhibition of STAT3 phosphorylation
      preferentially induced cytotoxicity in CD24(+) cells. In vivo JAK2 inhibitor
      therapy dramatically reduced tumor metastases, and prolonged overall survival.
      These findings indicate that CD24(+) cells play a role in tumor migration and
      metastasis and support JAK2 as a therapeutic target in ovarian cancer.

PMID- 25969156
TI  - Population Dynamics and Conservation Implications of Decalepis arayalpathra (J.
      Joseph and V. Chandras.) Venter., a Steno Endemic Species of Western Ghats,
      India.
AB  - Decalepis arayalpathra, a critically endangered plant species, has a restricted
      and fragmented population in Southern Western Ghats, India. This study is a first
      attempt to evaluate genetic diversity and population structure in the nine wild
      populations of D. arayalpathra based on molecular pattern realized through the
      marker assays. Principal coordinate analysis (PCoA) and Nei's unweighted pair
      group method with arithmetic average (UPGMA)-based hierarchical clustering of
      both the marker assays suggest strong genetic clustering between the individuals
      corresponding to their geographical ranges. Mantel test also corroborates a close
      genetic proximity between genetic and geographic data (r = 0.389). Population
      genetic analysis revealed low levels of gene flow [inter-simple sequence repeat
      (ISSR) = 0.289 and random amplified polymorphic DNA (RAPD) = 0.847] between the
      populations, in line with high genetic differentiation (Gst = 0.531 with ISSR and
      0.440 with RAPD), which was also supported by analysis of molecular variance
      (AMOVA), that 54 % (ISSR) and 64 % (RAPD) total variation resided within
      populations. Bayesian model-based STRUCTURE analysis detected three genetic
      clusters showing the high degree of admixture within population. Based on the
      findings, such as inbreeding depression and the loss of genetic diversity,
      suggestions for conservation strategies are provided to preserve the genetic
      resources of this endangered species.

PMID- 25969155
TI  - In situ remineralizing effect of fluoride varnishes containing sodium
      trimetaphosphate.
AB  - OBJECTIVE: This study analyzed the effects of a fluoride (F) varnish supplemented
      with sodium trimetaphosphate (TMP) on the remineralization of caries-like lesions
      in situ. MATERIALS AND METHODS: Twelve subjects used palatal devices with
      demineralized enamel discs for 3 days, following a double-blind, crossover
      protocol. Test groups included placebo (no F or TMP), 5% NaF and 5% NaF/5% TMP
      varnishes. The percentage of surface hardness recovery (%SHR) and cross-sectional
      hardness (DeltaKHN) were determined. RESULTS: Significant differences were
      observed among all varnishes regarding %SHR and DeltaKHN. The highest %SHR and
      the lowest DeltaKHN were seen for the 5% NaF/5% TMP varnish, followed by 5% NaF
      and placebo. CONCLUSION: The remineralizing effect of a 5% NaF varnish is
      significantly enhanced when associated with TMP. CLINICAL RELEVANCE: The
      reduction in the subsurface lesion area of enamel treated with the TMP-containing
      varnish implies that cavities would take longer to develop or might not develop
      at all depending on individual factors, resulting in lower net caries increments
      at individual and population levels.

PMID- 25969157
TI  - Extraction of Lipids from Chlorella saccharophila Using High-Pressure
      Homogenization Followed by Three Phase Partitioning.
AB  - Commercial exploitation of microalgae for biofuel and food ingredients is
      hindered due to laborious extraction protocols and use of hazardous chemicals.
      Production of lipids in the microalga grown in modified BG11 medium was evaluated
      to arrive at the appropriate harvesting conditions. The use of three phase
      partitioning (TPP) as a green approach for extraction of lipids from Chlorella
      saccharophila was investigated. Cells disrupted by probe sonication were used for
      separation of lipids by TPP. The TPP-optimized conditions of 30 % ammonium
      sulfate, using slurry/t-butanol of 1:0.75 for 60 min at 25 to 35  degrees C,
      showed a lipid recovery of 69.05 +/- 3.12 % (w/w) as against 100 % (w/w) by using
      chloroform-methanol extraction. Subsequently, parameters of high-pressure
      homogenization for cell disruption were optimized for maximum recovery of lipids
      by TPP. A final recovery of 89.91 +/- 3.69 % (w/w) lipids was obtained along with
      ~1.26 % w/w carotenoids of dry biomass in the t-butanol layer and protein content
      of ~12 % w/w of dry biomass in the middle protein layer due to ammonium sulfate
      precipitation, after performing TPP under the optimized conditions.

PMID- 25969158
TI  - Driving simulator evaluation of drivers' response to intersections with dynamic
      use of exit-lanes for left-turn.
AB  - With the worsening of urban traffic congestion in large cities around the world,
      researchers have been looking for unconventional designs and/or controls to
      squeeze more capacity out of intersections, the most common bottlenecks of the
      road network. One of these innovative intersection designs, known as the exit
      lanes for left-turn (EFL), opens up exit-lanes to be used by left-turn traffic
      with the help of an additional traffic light installed at the median opening (the
      pre-signal). This paper studies how drivers respond to EFL intersections with a
      series of driving simulator experiments. In our experiments, 64 drivers were
      recruited and divided into two groups. One group is trained to use the EFL while
      the other group is not. In addition, four scenarios were considered with
      different sign and marking designs and traffic conditions in the experiments.
      Results indicate that drivers show certain amount of confusion and hesitation
      when encountering an EFL intersection for the first time. They can be overcome,
      however, by increasing exposure through driver education or by cue provided from
      other vehicles. Moreover, drivers unfamiliar with EFL operation can make a left
      turn using the conventional left-turn lanes as usual. The EFL operation is not
      likely to pose any serious safety risk of the intersection in real life
      operations. 

PMID- 25969159
TI  - Relationship between temperament, character and the autistic trait in parents of
      children with autistic spectrum disorder.
AB  - OBJECTIVE: Previous studies have revealed distinct features of autism, with
      higher harm avoidance and lower reward dependence and novelty seeking. It is
      assumed that high harm avoidance, and low novelty seeking, reward dependence,
      cooperativeness, and self-directedness are related with the broad autism
      phenotype, as seen in autistic individuals. METHOD: This study examined the
      association between the Temperament and Character Inventory (TCI) and the Autism
      Spectrum Quotient (AQ), in parents of children with ASD. RESULT: There was
      significant correlation between total AQ and total harm avoidance,
      cooperativeness, and self-directedness (p < 0.05). In the stepwise analysis, self
      directedness and education emerged significantly (F(2,67) = 19.71, p < .005).
      This model modestly explained 35% of variance (Adjusted R(2) = .350). CONCLUSION:
      Our findings suggest that self-directedness may be an autistic trait.

PMID- 25969160
TI  - No evidence for metabolic syndrome and lipid profile differences in patients
      suffering from bipolar I disorder with and without suicide attempts.
AB  - OBJECTIVE: The aim of the present study was to provide further evidence of (1)
      metabolic syndrome and blood lipid profile differences between suicide attempting
      and non-attempting patients with bipolar disorder (BPD) I and to assess these
      differences (2) as a function of acute depressive or manic phase. METHODS: Fifty
      inpatients (mean age: 36.14 years 48% males) with BPD I took part in the study.
      After recruitment, patients were clustered in four groups: 13 suicide attempters
      (SAs) assessed during a manic phase, 12 SAs assessed during a depressive phase,
      15 non-SAs assessed during a manic phase, and 10 non-SAs assessed during a
      depressive phase. Body mass index (BMI), metabolic syndrome, blood pressure,
      blood lipids (cholesterol, high- and low-density lipids, and triglyceride), and
      fasting blood sugar were assessed. RESULTS: Neither metabolic syndrome, blood
      lipid values, fasting blood sugar, nor BMI or blood pressure differed between the
      SAs and non-SAs, or between patients in an acute manic phase and those in a
      depressed phase. The overall prevalence of metabolic syndrome was 26.0%.
      CONCLUSION: Among patients with BPD I neither the occurrence of metabolic
      syndrome nor lipid values or fasting blood sugar are reliable biomarkers of
      suicidal behavior during either acute depressive or manic phase.

PMID- 25969161
TI  - Thermal Degradation Kinetics Modeling of Benzophenones and Xanthones during High
      Temperature Oxidation of Cyclopia genistoides (L.) Vent. Plant Material.
AB  - Degradation of the major benzophenones, iriflophenone-3-C-glucoside-4-O-glucoside
      and iriflophenone-3-C-glucoside, and the major xanthones, mangiferin and
      isomangiferin, of Cyclopia genistoides followed first-order reaction kinetics
      during high-temperature oxidation of the plant material at 80 and 90  degrees C.
      Iriflophenone-3-C-glucoside-4-O-glucoside was shown to be the most thermally
      stable compound. Isomangiferin was the second most stable compound at 80  degrees
      C, while its degradation rate constant was influenced the most by increased
      temperature. Mangiferin and iriflophenone-3-C-glucoside had comparable
      degradation rate constants at 80  degrees C. The thermal degradation kinetic
      model was subsequently evaluated by subjecting different batches of plant
      material to oxidative conditions (90  degrees C/16 h). The model accurately
      predicted the individual contents of three of the compounds in aqueous extracts
      prepared from oxidized plant material. The impact of benzophenone and xanthone
      degradation was reflected in the decreased total antioxidant capacity of the
      aqueous extracts, as determined using the oxygen radical absorbance capacity and
      DPPH(*) scavenging assays. 

PMID- 25969162
TI  - Constipation prophylaxis reduces length of stay in elderly hospitalized heart
      failure patients with home laxative use.
AB  - BACKGROUND AND AIM: Elderly, hospitalized patients suffer disproportionately from
      constipation; however, little data suggest that constipation prophylaxis reduces
      length of stay (LOS). We performed a retrospective analysis of elderly patients
      admitted to our hospital with congestive heart failure (CHF) to determine the
      effects of constipation prophylaxis on LOS. METHODS: Patients >= 65 years old
      admitted with the diagnosis of CHF in 2012 were evaluated for home and hospital
      laxative use on admission. Our primary outcome was LOS. We used linear regression
      modeling to independently evaluate the impact of constipation prophylaxis on LOS.
      RESULTS: Among 618 patients who were eligible for our study, 201 (32.5%) were
      using laxatives at home, whereas 254 (41.1%) were started on a prophylactic
      laxative on admission. There was no significant difference in LOS between
      patients receiving prophylaxis versus those who did not (P = 0.32). Patients with
      home laxative use had a 1 day longer LOS compared to those without laxative use
      (6 vs 5, P = 0.03). Among patients with home laxative use, there were 2 days
      longer LOS in those who were not given constipation prophylaxis on admission (8
      vs 6, P = 0.002). After multivariate adjustment, failure to use constipation
      prophylaxis in patients with home laxative use was the only independent predictor
      of increased LOS (P = 0.03). CONCLUSIONS: Among elderly patients admitted for CHF
      exacerbations, failure to use constipation prophylaxis in patients with home
      laxative use is associated with a significantly longer LOS. Our data suggest that
      routine use of bowel prophylaxis for elderly CHF patients with preexisting
      constipation may reduce LOS.

PMID- 25969163
TI  - Persulfides: current knowledge and challenges in chemistry and chemical biology.
AB  - Recent studies conducted in hydrogen sulfide (H2S) signaling have revealed
      potential importance of persulfides (RSSH) in redox biology. The inherent
      instability of RSSH makes these species difficult to study and sometimes
      controversial results are reported. In this review article we summarize known
      knowledge about both small molecule persulfides and protein persulfides. Their
      fundamental physical and chemical properties such as preparation/formation and
      reactivity are discussed. The biological implications of persulfides and their
      detection methods are also discussed. 

PMID- 25969164
TI  - Emotional, physical and sexual violence among Sami and non-Sami populations in
      Norway: The SAMINOR 2 questionnaire study.
AB  - AIMS: To assess the prevalence and investigate ethnic differences of emotional,
      physical and sexual violence among a population of both Sami and non-Sami in
      Norway. METHODS: Our study was based on the SAMINOR 2 study, a population-based
      survey on health and living conditions in multiethnic areas with both Sami and
      non-Sami populations in Central and Northern Norway. Our study includes a total
      of 11,296 participants: 2197 (19.4%) Sami respondents and 9099 (80.6 %) non-Sami
      respondents. RESULTS: Almost half of the Sami female respondents and one-third of
      the non-Sami female respondents reported any violence (any lifetime experience of
      violence). Sami women were more likely to report emotional, physical and sexual
      violence than non-Sami women. More than one-third of the Sami men compared with
      less than a quarter of non-Sami men reported having experienced any violence in
      their life. Sami men were more likely to report emotional and physical violence
      than non-Sami men. However, ethnicity was not significantly different regarding
      sexual violence experienced among men. Violence was typically reported to have
      occurred in childhood. Sami participants were more likely to report having
      experienced violence in the past 12 months. For all types of violence, the
      perpetrator was typically known to the victim. CONCLUSIONS: Regardless of gender,
      Sami respondents were more likely to report interpersonal violence. The
      prevalence of any violence was substantial in both ethnic groups and for both
      genders; it was highest among Sami women.

PMID- 25969165
TI  - The incidence of acute gastrointestinal illness in Sweden.
AB  - AIMS: The aim of this study was to estimate the self-reported domestic incidence
      of acute gastrointestinal illness in the Swedish population irrespective of route
      of transmission or type of pathogen causing the disease. Previous studies in
      Sweden have primarily focused on incidence of acute gastrointestinal illness
      related to consumption of contaminated food and drinking water. METHODS: In May
      2009, we sent a questionnaire to 4000 randomly selected persons aged 0-85 years,
      asking about the number of episodes of stomach disease during the last 12 months.
      To validate the data on symptoms, we compared the study results with anonymous
      queries submitted to a Swedish medical website. RESULTS: The response rate was
      64%. We estimated that a total number of 2744,778 acute gastrointestinal illness
      episodes (95% confidence intervals 2475,641-3013,915) occurred between 1 May 2008
      and 30 April 2009. Comparing the number of reported episodes with web queries
      indicated that the low number of episodes during the first 6 months was an effect
      of seasonality rather than recall bias. Further, the result of the recall bias
      analysis suggested that the survey captured approximately 65% of the true number
      of episodes among the respondents. CONCLUSIONS: The estimated number of Swedish
      acute gastrointestinal illness cases in this study is about five times higher
      than previous estimates this study provides valuable information on the incidence
      of gastrointestinal symptoms in Sweden, irrespective of route of transmission,
      indicating a high burden of acute gastrointestinal illness, especially among
      children, and large societal costs, primarily due to production losses.

PMID- 25969166
TI  - Drug-related causes of death: Socioeconomic and demographic characteristics of
      the deceased.
AB  - AIM: The aim of this study was to describe subgroups of those who died from a
      drug-related cause of death employing demographic and socioeconomic data.
      METHODS: A total of 1,628 persons with registered drug-related deaths in the
      Norwegian Cause of Death Registry between 2003 and 2009 were matched with
      research registers of data on demographic and socioeconomic factors during the
      five years prior to their deaths. RESULTS: Three equal-sized clusters were
      identified: persons with very low socioeconomic status, disability pensioners and
      people on the edge of the workforce. CONCLUSIONS: Socioeconomic situation prior
      to drug-related deaths was more heterogeneous than expected. Greater knowledge
      about the members of the disability pensioner and the edge of the workforce
      clusters must be established in order to make prevention efforts towards these
      groups more precise and goal oriented.

PMID- 25969167
TI  - Trends in out-of-hospital ischemic heart disease mortality for the 25-64 year old
      population of Kaunas, Lithuania, based on data from the 1988-2012 Ischemic Heart
      Disease Registry.
AB  - AIM: The aim of the study was to evaluate trends in out-of-hospital ischemic
      heart disease (IHD) mortality in the Kaunas, Lithuania population aged 25-64,
      from 1988 to 2012. METHODS: The registry was maintained according to the World
      Health Organisation (WHO) recommendations for the multinational MONICA
      (MONItoring of trends and determinants in CArdiovascular disease) project. We
      analysed out-of-hospital deaths from IHD, by sex and age groups, using the linear
      logistic regression model for identifying trends. RESULTS: In 1988-2012, the out
      of-hospital IHD deaths in Kaunas accounted for 78.4% and 68.4%, on average, of
      all IHD deaths in men and women aged 25-64, respectively. During the study
      period, the out-of-hospital IHD mortality for the Kaunas population aged 25-64
      was 134.5 per 100,000 men and 18.2 per 100,000 women. From 1988 to 2012, the out
      of-hospital IHD mortality for men and women aged 25-64 tended to decline by, on
      average, 8.3% per year (p = 0.269) and 16.2% per year (p = 0.101), respectively;
      whereas the corresponding rates for men aged 25-44 were declining significantly,
      by 22.5% per year (p = 0.047). The most significant changes in out-of-hospital
      IHD mortality were among men aged 25-44 with no previous history of acute
      myocardial infarction (AMI), in whom the out-of-hospital IHD mortality was
      significantly declining, by 21.3% per year (p = 0.015); whereas the corresponding
      rates for men aged 45-54 with a previous history of AMI tended to decline by
      20.4% per year (p = 0.114). CONCLUSIONS: In 1988-2012, the out-of-hospital IHD
      deaths of younger men and middle-aged women accounted for the highest percentage
      of all IHD deaths; and a higher proportion of both men and women with no previous
      history of AMI, as compared to the proportion of those with a previous history of
      AMI.

PMID- 25969168
TI  - Clinical Application of Induced Pluripotent Stem Cells in Cardiovascular
      Medicine.
AB  - Induced pluripotent stem cells (iPSCs) are generated by reprogramming human
      somatic cells through the overexpression of four transcription factors: Oct4,
      Sox2, Klf4 and c-Myc. iPSCs are capable of indefinite self-renewal, and they can
      differentiate into almost any type of cell in the body. These cells therefore
      offer a highly valuable therapeutic strategy for tissue repair and regeneration.
      Recent experimental and preclinical research has revealed their potential for
      cardiovascular disease diagnosis, drug screening and cellular replacement
      therapy. Nevertheless, significant challenges remain in terms of the development
      and clinical application of human iPSCs. Here, we review current progress in
      research related to patient-specific iPSCs for ex vivo modeling of cardiovascular
      disorders and drug screening, and explore the potential of human iPSCs for use in
      the field of cardiovascular regenerative medicine.

PMID- 25969169
TI  - A solid-phase combinatorial approach for indoloquinolizidine-peptides with high
      affinity at D(1) and D(2) dopamine receptors.
AB  - Ligands acting at multiple dopamine receptors hold potential as therapeutic
      agents for a number of neurodegenerative disorders. Specifically, compounds able
      to bind at D1R and D2R with high affinity could restore the effects of dopamine
      depletion and enhance motor activation on degenerated nigrostriatal dopaminergic
      systems. We have directed our research towards the synthesis and characterisation
      of heterocycle-peptide hybrids based on the indolo[2,3-a]quinolizidine core. This
      privileged structure is a water-soluble and synthetically accessible scaffold
      with affinity for diverse GPCRs. Herein we have prepared a solid-phase
      combinatorial library of 80 indoloquinolizidine-peptides to identify compounds
      with enhanced binding affinity at D2R, a receptor that is crucial to re-establish
      activity on dopamine-depleted degenerated GABAergic neurons. We applied
      computational tools and high-throughput screening assays to identify 9a{1,3,3} as
      a ligand for dopamine receptors with nanomolar affinity and agonist activity at
      D2R. Our results validate the application of indoloquinolizidine-peptide
      combinatorial libraries to fine-tune the pharmacological profiles of multiple
      ligands at D1 and D2 dopamine receptors. 

PMID- 25969170
TI  - Design, synthesis and anticholinesterase activity of novel benzylidenechroman-4
      ones bearing cyclic amine side chain.
AB  - A series of 3-(4-(aminoalkoxy)benzylidene)-chroman-4-ones 7a-r were designed and
      synthesized as analogs of homoisoflavonoids which are well known natural products
      with diverse pharmacological properties related to Alzheimer's disease. The in
      vitro anti-cholinesterase activity of designed compounds 7a-r against AChE and
      BuChE, revealed that compounds bearing piperidinylethoxy residue showed potent
      activity against AChE at sub-micromolar level (IC50 values = 0.122-0.207 MUM),
      more potent than reference drug tacrine. The structure-activity relationships
      study of piperidinylethoxy series demonstrated that the selectivity and
      physicochemical properties of compounds could be optimized by selection of a
      proper substituent on the C-7 position of chroman ring, while the high potency of
      the molecule against AChE was reserved. 

PMID- 25969171
TI  - Organoselenocyanates and symmetrical diselenides redox modulators: Design,
      synthesis and biological evaluation.
AB  - Oxidative stress (OS) and disturbed intracellular redox balance have been
      predominantly observed in different types of cancer, including hepatocellular
      carcinoma (HCC). Agents which can stop OS multi-stressor events and modulate the
      intracellular redox state are becoming a major focus in HCC prevention. Among
      them, compounds with glutathione peroxidase (GPx)-like activity are of
      particularly concern. We herein report the synthesis of novel series of
      organoselenocyanates and symmetrical diselenide antioxidants, inspired by the
      natural redox enzyme, GPx and the synthetic organoselenium ebselen antioxidants.
      Their cytotoxic activity was evaluated against Hep G2 cells and their
      antimicrobial activities were evaluated against Candida albicans (C. albicans)
      fungus as well as against Escherichia coli (E. coli) and Staphylococcus aureus
      (S. aureus), gram-negative and gram-positive bacteria, respectively. These
      compounds were also tested for their antioxidant activities using 2,2-diphenyl-1
      picrylhydrazyl (DPPH), GPx-like activity and bleomycin dependent DNA damage
      assays and a basic structure-activity relationship was subsequently established.
      The physicochemical parameters and drug-likeness were computed employing the
      Molinspiration online property calculation toolkit and MolSoft software.
      Interestingly, some compounds proved to be more cytotoxic than ebselen and the
      known anticancer drug 5-Fu and in the same time they showed similar, sometime
      even more, antifungal activity than the reference antifungal drugs. Among these
      compounds, compound 16 was considered to be the most interesting with free
      radical-scavenging activity comparable to ascorbic acid and a GPx-like activity
      similar to ebselen. As most of these compounds comply with Lipinski's Rule of
      Five, they promise good bioavailability, which needs to be studied as part of
      future investigations. 

PMID- 25969172
TI  - Circadian typology and the Alternative Five-Factor Model of personality.
AB  - Two studies were carried out to explore the relationship between circadian
      typology and the Alternative Five-Factor Model of personality. In the first
      study, 379 participants (232 females) were administered the reduced version of
      the Morningness-Eveningness Questionnaire and the Zuckerman-Kuhlman Personality
      Questionnaire. Evening types reported higher impulsive sensation-seeking scores
      than morning and intermediate types, whereas morning types scored higher than
      evening types on activity factor. In the second study, the association between
      morningness and activity personality factor was verified through the objective
      actigraphic monitoring of the rest-activity cycle. Actigraphy allowed us to
      operationalise both circadian typology, through the computing of midpoint of
      sleep (early values, expressed in hours and minutes, correspond to an advanced
      phase of the sleep/wake cycle), and activity factor by the means of motor
      activity recording. Fifty-one individuals (30 females) wore an actigraph on the
      nondominant wrist continuously for 1 week. A negative correlation was observed
      between midpoint of sleep and mean diurnal motor activity, demonstrating that an
      early phase of the sleep/wake cycle (i.e. morningness preference) was related to
      higher diurnal motor activity. Assessed both subjectively and objectively, the
      results of both studies highlight a significant relationship between morningness
      and activity personality factor. 

PMID- 25969173
TI  - Photoluminescence investigation of strictly ordered Ge dots grown on pit
      patterned Si substrates.
AB  - We investigate the optical properties of ordered Ge quantum dots (QDs) by means
      of micro-photoluminescence spectroscopy (PL). These were grown on pit-patterned
      Si(001) substrates with a wide range of pit-periods and thus inter QD-distances
      (425-3400 nm). By exploiting almost arbitrary inter-QD distances achievable in
      this way we are able to choose the number of QDs that contribute to the PL
      emission in a range between 70 and less than three QDs. This well-defined system
      allows us to clarify, by PL-investigation, several points which are important for
      the understanding of the formation and optical properties of ordered QDs. We
      directly trace and quantify the amount of Ge transferred from the surrounding
      wetting layer (WL) to the QDs in the pits. Moreover, by exploiting different pit
      shapes, we reveal the role of strain-induced activation energy barriers that have
      to be overcome for charge carriers generated outside the dots. These need to
      diffuse between the energy minimum of the WL in and between the pits, and the one
      in the QDs. In addition, we demonstrate that the WL in the pits is already
      severely intermixed with Si before upright QDs nucleate, which further enhances
      intermixing of ordered QDs as compared to QDs grown on planar substrates.
      Furthermore, we quantitatively determine the amount of Ge transferred by surface
      diffusion through the border region between planar and patterned substrate. This
      is important for the growth of ordered islands on patterned fields of finite
      size. We highlight that the Ge WL-facets in the pits act as PL emission centres,
      similar to upright QDs. 

PMID- 25969174
TI  - Synthesis, crystal structure and investigation of mononuclear copper(II) and
      zinc(II) complexes of a new carboxylate rich tripodal ligand and their
      interaction with carbohydrates in alkaline aqueous solution.
AB  - A new carboxylate rich asymmetric tripodal ligand, N-[2-carboxybenzomethyl]-N
      [carboxymethyl]-beta-alanine (H3camb), and its di-copper(II), (NH4)2[1]2, and di
      zinc(II), ((CH3)4N)2[2]2, complexes have been synthesized as carbohydrate binding
      models in aqueous solutions. The ligand and complexes have been fully
      characterized using several techniques, including single crystal X-ray
      diffraction. The interactions of (NH4)2[1]2 and ((CH3)4N)2[2]2 with D-glucose, D
      mannose, D-xylose and xylitol in aqueous alkaline media were investigated using
      UV-Vis and (13)C-NMR spectroscopic techniques, respectively. The molar
      conductance, NMR and ESI-MS studies indicate that the complexes dissociate in
      solution to produce the respective complex anions, 1(-) and 2(-). Complexes 1(-)
      and 2(-) showed chelating ability towards the naturally abundant and biologically
      relevant sugars, D-glucose, D-mannose, D-xylose, and xylitol. The complex ions
      bind to one molar equivalent of the sugars, even in the presence of
      stoichiometric excess of the substrates, in solution. Experimentally obtained
      spectroscopic data and computational results suggest that the substrates bind to
      the metal center in a bidentate fashion. Apparent binding constant values,
      pK(app), between the complexes and the substrates were determined and a specific
      mode of substrate binding is proposed. The pK(app) and relativistic density
      functional theory (DFT) calculated Gibbs free energy values indicate that D
      mannose displayed the strongest interaction with the complexes. Syntheses,
      characterizations, detailed substrate binding studies using spectroscopic
      techniques, single crystal X-ray diffraction and geometry optimizations of the
      complex-substrates with DFT calculations are also reported.

PMID- 25969175
TI  - Low Expression of miR-448 Induces EMT and Promotes Invasion by Regulating ROCK2
      in Hepatocellular Carcinoma.
AB  - BACKGROUND/AIMS: miR-448 has been reported to exhibit abnormal expression in
      hepatocellular carcinoma (HCC), however, the essential role of miR-448 in HCC
      progression is still unclear. METHODS: real-time PCR was used to detect the
      expression of miRNAs and candidate genes in HCC samples (n=117). miR-448 mimics
      and inhibitor were tansfected in human HCC cells. The transwell assay was used to
      examine the cell invasive ability. The regulation mechanism was confirmed by
      luciferase reporter assay. The markers of EMT were detected by using Western
      blot. RESULTS: miR-448 was decreased in HCC samples and associated with HCC
      development. Inhibition of miR-448 significantly promoted cell invasion, while
      the effect of miR-448 up-regulation was reverse. miR-448 could regulate ROCK2 in
      hepatocellular carcinoma. Knockdown of ROCK2 expression partially reversed the
      effect of miR-448 inhibitor. Abnormal expression of miR-448 could regulate the
      markers of epithelial-mesenchymal transition (EMT). CONCLUSIONS: miR-448 may
      contribute to the progression of HCC via regulating ROCK2 expression.

PMID- 25969176
TI  - The value of liver-based standardized uptake value and other quantitative 18F-FDG
      PET-CT parameters in neoadjuvant therapy response in patients with locally
      advanced rectal cancer: correlation with histopathology.
AB  - AIM: We aimed to investigate the value of PET-CT in therapy response and the
      correlation of quantitative PET parameters with histopathologic results in
      patients with locally advanced rectal cancer (LARC) before and after neoadjuvant
      chemoradiotherapy. We also analyzed the correlation of PET-CT parameters between
      Ki-67 and glucose transporter 1 (GLUT1). PATIENTS AND METHODS: A total of 29
      patients diagnosed with LARC who had undergone a biopsy between 2009 and 2012
      were included in our study. Quantitative PET parameters [standardized uptake
      value (SUV)max-mean, lean body mass SUV(max-mean), tumor/liver SUV, retention
      index , and [INCREMENT]SUV(max)] were measured before and after therapy using PET
      CT. Tumor regression grade (TRG) was evaluated according to Wheeler's
      classification. Patients in grade 1 were considered responders, whereas patients
      at grades 2 and 3 were considered nonresponders. Immunohistochemical staining
      with Ki-67 and GLUT1 was performed on biopsy and surgical specimens. The
      correlation between staining ratios and SUV was also investigated. RESULTS: SUV
      parameters were significantly decreased after therapy (P < 0.001). Twelve (41%)
      patients were at TRG1, 10 (35%) were at TRG2, and seven (24%) were at TRG3. A
      cutoff SUV(max) of 5.05 to discriminate between responders and nonresponders
      after treatment revealed a sensitivity of 57%, specificity of 73%, negative
      predictive value of 65%, positive predictive value of 67%, and accuracy of 66%.
      Using a cutoff of 3.55 for the SUV(mean) (standardized measurement of SUV with
      1.2-cm-diameter region of interest) revealed a sensitivity, specificity, negative
      predictive value, positive predictive value, and accuracy of 67, 76, 67, 76, and
      72%, respectively. For a cutoff of 1.95 for the tumor SUV(mean)/liver SUV(mean),
      these diagnostic values after therapy were 73, 78, 82, 67, and 76%, respectively.
      We found a moderate correlation between liver-based SUV(max) (r = -0.35, P =
      0.019) and SUV(mean )(r = -0.31, P = 0.036) with GLUT1 after therapy.
      Quantitative PET parameters and retention index were moderately correlated with
      Ki-67. CONCLUSION: PET-CT is a useful method for assessing the response to
      neoadjuvant chemoradiotherapy in patients with LARC. The most significant
      parameter for assessing treatment response using SUV parameters is the
      tumor/liver ratio.

PMID- 25969177
TI  - Mediation of an efficacious HIV risk reduction intervention for South African
      men.
AB  - "Men, Together Making a Difference!" is an HIV/STD risk-reduction intervention
      that significantly increased self-reported consistent condom use during vaginal
      intercourse compared with a health-promotion attention-control intervention among
      men (N = 1181) in Eastern Cape Province, South Africa. The present analyses were
      designed to identify mediators of the intervention's efficacy. The potential
      mediators were Social Cognitive Theory (SCT) constructs that the intervention
      targeted, including several aspects of condom-use self-efficacy, outcome
      expectancies, and knowledge. Mediation was assessed using a product-of
      coefficients approach where an alpha path (the intervention's effect on the
      potential mediator) and a beta path (the potential mediator's effect on the
      outcome of interest, adjusting for intervention) were estimated independently in
      a generalized estimating equations framework. Condom-use negotiation self
      efficacy, technical-skill self-efficacy, and impulse-control self-efficacy were
      significant mediators. Although not mediators, descriptive norm and expected
      friends' approval of condom use predicted subsequent self-reported condom use,
      whereas the expected approval of sexual partner did not. The present results
      suggest that HIV/STD risk-reduction interventions that draw upon SCT and that
      address self-efficacy to negotiate condom use, to apply condoms correctly, and to
      exercise sufficient control when sexually aroused to use condoms may contribute
      to efforts to reduce sexual risk behavior among South African men. Future
      research must examine whether approaches that build normative support for condom
      use among men's friends are also efficacious. 

PMID- 25969178
TI  - Pre-exposure Prophylaxis Adherence Measured by Plasma Drug Level in MTN-001:
      Comparison Between Vaginal Gel and Oral Tablets in Two Geographic Regions.
AB  - Despite strong evidence that daily oral pre-exposure prophylaxis (PrEP) reduces
      HIV risk, effectiveness across studies has varied. Inconsistent adherence
      constitutes one explanation. Efforts to examine adherence are limited when they
      rely on self-reported measures. We examined recent adherence as measured by
      plasma tenofovir (TFV) concentration in participants of MTN-001, a phase 2 cross
      over trial comparing oral tablet and vaginal gel formulations of TFV among 144
      HIV-uninfected women at sites in the United States (U.S.) and sub-Saharan Africa
      (SSA). Adherence to daily product use was higher in the U.S. than in the SSA
      sites. Within region, however, adherence was similar between products. In the
      U.S., gel adherence was higher among married women, and lower among women using
      male condoms and injectable contraceptives. At the SSA sites, gel adherence was
      lower for younger women. Inconsistent adherence points to challenges in use of
      daily PrEP, even during a trial of short duration.

PMID- 25969179
TI  - HIV Testing Among Spanish Youth: Analysis of the Mediating Role of the Big Five
      Personality and Other Psychological Factors.
AB  - Early diagnosis of HIV improves the effectiveness of treatments and stops the
      progression of the disease. The influence of personality and other psychological
      variables in testing for HIV is analyzed. The first part of the study is composed
      of 4,929 young people (M age = 20.45, SD = 2.16). For the second part, young
      heterosexuals who participated in a broader project on HIV prevention were
      selected (n = 240, M age = 20.78, SD = 2.29). Only 23.3 % of the total sample
      have ever been tested for HIV antibodies. The main reason for not testing was
      fear of positive result (25.4 %). Statistically significant differences in
      Agreeableness (p = .027), Trust (p = .022) and Straightforwardness (p = .024)
      were found between HIV-tested and not HIV-tested youth. Trust explained 3.3 % of
      variance of HIV-test. Knowing barriers to testing and individual differences
      could be useful in developing preventive campaigns. 

PMID- 25969180
TI  - Informal Caregiver Characteristics Associated with Viral Load Suppression Among
      Current or Former Injection Drug Users Living with HIV/AIDS.
AB  - Few studies have examined the association between having an informal (unpaid)
      caregiver and viral suppression among persons living with HIV/AIDS (PLHIV) who
      are on antiretroviral therapy. The current study examined relationships between
      caregivers' individual and social network characteristics and care recipient
      viral suppression. Baseline data were from the BEACON study caregivers and their
      HIV seropositive former or current drug using care recipients, of whom 89 % were
      African American (N = 258 dyads). Using adjusted logistic regression, care
      recipient's undetectable viral load was positively associated with caregiver's
      limited physical functioning and negatively associated with caregivers having few
      family members to turn to for problem solving, a greater number of current drug
      users in their network, and poorer perceptions of the care recipient's mental
      health. Results further understandings of interpersonal relationship factors
      important to PLHIV's health outcomes, and the need for caregiving relationship
      focused intervention to promote viral suppression among PLHIV. 

PMID- 25969181
TI  - Repeat Use of Post-exposure Prophylaxis for HIV Among Nairobi-Based Female Sex
      Workers Following Sexual Exposure.
AB  - As ART-based prevention becomes available, effectively targeting these
      interventions to key populations such as female sex workers (FSW) will be
      critical. In this study we analyze patterns of repeated post-exposure prophylaxis
      (PEP) access in the context of a large FSW program in Nairobi. During close to
      6000 person-years of follow-up, 20 % of participants (n = 1119) requested PEP at
      least once and 3.7 % requested PEP more than once. Repeat PEP users were younger,
      had a higher casual partner volume, and were more likely to use condoms with
      casual and regular partners, have a regular partner, and test for HIV prior to
      enrolment. Barriers to PEP included stigma, side effects, and lack of knowledge,
      suggesting repeated promotion may be required for higher rates of uptake. A small
      subset of FSW, potentially those with heightened risk perception, showed a higher
      frequency of PEP use; these individuals may be most amenable to rollout of pre
      exposure prophylaxis.

PMID- 25969184
TI  - Development of measuring diffusion coefficients by digital holographic
      interferometry in transparent liquid mixtures.
AB  - As for the measurement of diffusion coefficient in transparent liquids by digital
      holographic interferometry, there are many kinds depending on the mathematical
      model and experimental setup. The method of using the distance of the peaks in
      concentration difference profile to determine diffusion coefficient by Mach
      Zehnder interferometric experimental setup, is easy to handle. In order to
      improve the accuracy and convenience of measurement in this method, we combine
      procedures of hologram analysis used by Mialdun et al (2011) and those by He et
      al (2009). By using polynomial to fit the continuous phase difference
      (interference phase) of object beam, it can be more convenient and accurate to
      determine the distance between the two peaks. Besides, the shift of initial time
      has been discussed as a separated topic at the first time and two functions for
      minimization have been given for determination of the initial time in this paper.
      With the development, diffusion coefficient of KCl in water at 0.33mol/L and 25 
      degrees C has been measured. The diffusion coefficient is 1.844 * 10(-9) m2/s
      with the uncertainty of +/- 0.012 * 10(-9) m2/s. Our measurement has more similar
      result with other methods than holographic interferometry. The relative
      uncertainty of diffusion coefficient in our experiment is less than 1% and total
      uncertainty of temperature is within +/- 0.04 K.

PMID- 25969185
TI  - Increasing single mode power of 1.3-MUm VCSELs by output coupling optimization.
AB  - We report on the single mode emission power enhancement of 1.3-MUm VCSELs by
      adjusting the reflectivity of the top GaAs-based DBR for output coupling
      optimization using selective removal of Bragg reflector layers. Devices with
      record single mode power of 6.8-mW at room temperature and 2.8-mW at 80 degrees
      C, with more than 30 dB single mode suppression ratio, have been obtained. 

PMID- 25969186
TI  - 10 Gb/s InP-based Mach-Zehnder modulator for operation at 2 MUm wavelengths.
AB  - We report on the first InP-based Mach-Zehnder modulator (MZM) employing quantum
      confined Stark effect (QCSE) for operation around 2000 nm. The polarization
      sensitive device is based on 15 compressively strained quantum wells and achieves
      an electro-optic (EO) bandwidth of at least 9 GHz, with a DC extinction ratio of
      ~9 dB, and a V(pi)L ~9.6 V.mm. We demonstrate back-to-back communication with a
      10 Gb/s pseudo-random bit sequence (PRBS) of length 2(7)-1 at a wavelength around
      2000 nm.

PMID- 25969183
TI  - Serum Pentraxin-3 Level in Patients Who Underwent Coronary Angiography and
      Relationship with Coronary Atherosclerosis.
AB  - OBJECTIVES: To evaluate the role of pentraxin-3 (PTX-3) in determining the
      presence and severity of coronary atherosclerosis in patients with coronary
      artery disease (CAD). SUBJECTS AND METHODS: Ninety-five patients (77 males and 18
      females) who underwent elective coronary angiography were enrolled in this study.
      Patients with heart failure, renal failure, diabetes and thyroid disease were
      excluded. The study population was divided into 3 groups: individuals with normal
      coronary arteries, patients with critical CAD (n = 35) and patients with
      noncritical CAD (n = 36). The association of PTX-3 levels with the presence and
      severity of CAD and the number of involved vessels were analyzed. RESULTS: The
      mean age was 53.40 +/- 10.25 years. The PTX-3 levels were significantly higher in
      patients with CAD than without CAD (146.48 +/- 48.52 vs. 109.83 +/- 49.06 pg/ml,
      p < 0.001). A statistically significant difference was found among the 3 groups
      regarding the severity of CAD (165.66 +/- 49.10, 127.83 +/- 40.51 and 109.83 +/-
      49.06 pg/ml, p < 0.001, respectively). The serum PTX-3 levels in normal arteries
      were 110.4 +/- 48.11 pg/ml, in single-vessel disease 132.35 +/- 32.96 pg/ml, in 2
      vessel disease 142.57 +/- 55.88 pg/ml, in 3-vessel disease 156.07 +/- 50.53
      pg/ml, and in 3-vessel disease 160.50 +/- 30.41 pg/ml. After adjusting for
      baseline confounders, older age (OR = 1.107, 95% CI = 1.027-1.193, p = 0.008) and
      higher PTX-3 levels (OR = 1.017, 95% CI = 1.003-1.032, p = 0.021) were detected
      as significant predictors for the presence of CAD. CONCLUSIONS: Higher PTX-3
      levels were associated with the presence of CAD and its increased severity in
      clinically stable patients. Higher PTX-3 levels may be regarded as a novel
      diagnostic predictor and may offer therapeutic options in the clinic.

PMID- 25969182
TI  - Depression and Social Stigma Among MSM in Lesotho: Implications for HIV and
      Sexually Transmitted Infection Prevention.
AB  - Social stigma is common among men who have sex with men (MSM) across Sub-Saharan
      Africa, and may influence risks for HIV and sexually transmitted infections
      (STIs) via its association with depression. We conducted a cross-sectional study
      of 530 MSM in Lesotho accrued via respondent-driven sampling. Using generalized
      structural equation models we examined associations between stigma, social
      capital, and depression with condom use and testing positive for HIV/STIs.
      Depression was positively associated with social stigma experienced or perceived
      as a result of being MSM. In contrast, increasing levels of social cohesion were
      negatively associated with depression. Social stigma was associated with testing
      positive for HIV; however, this association did not appear to be mediated by
      depression or condom use. These data suggest a need for integrated HIV and mental
      health care that addresses stigma and discrimination and facilitates positive
      social support for MSM. 

PMID- 25969187
TI  - Frequency-resolved optical gating for characterization of VUV pulses using
      ultrafast plasma mirror switching.
AB  - We propose and experimentally demonstrate a method for characterizing vacuum
      ultraviolet (VUV) pulses based on time-resolved reflection spectroscopy of fused
      silica pumped by an intense laser pulse. Plasma mirror reflection is used as an
      ultrafast optical switch, which enables us to measure frequency-resolved optical
      gating (FROG) traces. The VUV temporal waveform can be retrieved from the
      measured FROG trace using principal component generalized projections algorithm
      with modification. The temporal profile of the plasma mirror reflectivity is also
      extracted simultaneously. 

PMID- 25969188
TI  - Parallel-incidence-type waveguide-mode sensor with spectral-readout setup.
AB  - A waveguide-mode sensor of the spectral-readout type can be used to detect
      changes in the complex refractive index in the vicinity of the surface of a
      sensing plate by observing the change in the spectrum of light reflected on the
      surface. The sensor's configuration can be simplified by adopting a parallel
      incidence-type optical setup. To obtain a high sensitivity, the optimization of
      the sensing-plate structure, incidence angle, and detection wavelength band is
      essential for the sensor. In the present report, the results predicted by
      simulations are compared with experimental results in order to evaluate their
      validity. A discussion of the optimal design for the parallel-incidence-type
      sensor is also presented, according to the results obtained. 

PMID- 25969189
TI  - Reflective coating optimization for interferometric detectors of gravitational
      waves.
AB  - Brownian fluctuations in the highly reflective test-mass coatings are the
      dominant noise source, in a frequency band from a few tens to a few hundreds Hz,
      for Earth-bound detectors of Gravitational Waves. Minimizing such noise is
      mandatory to increase the visibility distance of these instruments, and
      eventually reach their quantum-limited sensitivity. Several strategies exist to
      achieve this goal. Layer thickness and material properties optimization have been
      proposed and effectively implemented, and are reviewed in this paper, together
      with other, so far less well developed, options. The former is the simplest
      option, yielding a sensible noise reduction with limited technological
      challenges; the latter is more technologically demanding, but is needed for
      future (cryogenic) detectors. 

PMID- 25969190
TI  - THz holography in reflection using a high resolution microbolometer array.
AB  - We demonstrate a digital holographic setup for Terahertz imaging of surfaces in
      reflection. The set-up is based on a high-power continuous wave (CW) THz laser
      and a high-resolution (640 * 480 pixel) bolometer detector array. Wave
      propagation to non-parallel planes is used to reconstruct the object surface that
      is rotated relative to the detector plane. In addition we implement synthetic
      aperture methods for resolution enhancement and compare Fourier transform phase
      retrieval to phase stepping methods. A lateral resolution of 200 MUm and a
      relative phase sensitivity of about 0.4 rad corresponding to a depth resolution
      of 6 MUm are estimated from reconstructed images of two specially prepared test
      targets, respectively. We highlight the use of digital THz holography for surface
      profilometry as well as its potential for video-rate imaging. 

PMID- 25969191
TI  - Young's experiment with waves near zeros.
AB  - We report an interesting observation in the formation of Young's fringes from a
      two pinhole arrangement illuminated by waves from the neighborhood of a zero of
      an optical phase singularity. Spacing of the Young's fringes appears to defy the
      dependence of pin-hole separation. But for larger pinhole separation such an
      anomalous phenomenon is not discernible. The experiments show that the fringe
      spacing is governed by the stronger local phase gradient near the vortex core
      that also has a radial part. Many diffraction experiments reported so far have
      missed this aspect as the phase gradient in a vortex beam is normally considered
      to have only azimuthal and longitudinal components. This work reveals the vortex
      core structure and is the first experimental evidence to the existence of a
      radial component of this phase gradient. 

PMID- 25969192
TI  - Near-field investigation of the effect of the array edge on the resonance of loop
      frequency selective surface elements at mid-infrared wavelengths.
AB  - Mid-infrared scattering scanning near-field optical microscopy, in combination
      with far-field infrared spectroscopy, and simulations, was employed to
      investigate the effect of mutual-element coupling towards the edge of arrays of
      loop elements acting as frequency selective surfaces (FSSs). Two different square
      loop arrays on ZnS over a ground plane, resonant at 10.3 um, were investigated.
      One array had elements that were closely spaced while the other array had
      elements with greater inter-element spacing. In addition to the dipolar
      resonance, we observed a new emergent resonance associated with the edge of the
      closely-spaced array as a finite size effect, due to the broken translational
      invariance. 

PMID- 25969193
TI  - Spectrally-efficient all-optical OFDM by WSS and AWG.
AB  - We report on the transmission experiment of seven 12.5-GHz spaced all optical
      orthogonal frequency division multiplexed (AO-OFDM) subcarriers over a 35-km
      fiber link, using differential quadrature phase shift keying (DQPSK) modulation
      and direct detection. The system does not require chromatic dispersion
      compensation, optical time gating at the receiver (RX) or cyclic prefix (CP),
      achieving the maximum spectral efficiency. We use a wavelength selective switch
      (WSS) at the transmitter (TX) to allow subcarrier assignment flexibility and
      optimal filter shaping; an arrayed waveguide grating (AWG) AO-OFDM demultiplexer
      is used at the RX, to reduce the system cost and complexity. 

PMID- 25969194
TI  - Experimental demonstration of large capacity WSDM optical access network with
      multicore fibers and advanced modulation formats.
AB  - Towards the next generation optical access network supporting large capacity data
      transmission to enormous number of users covering a wider area, we proposed a
      hybrid wavelength-space division multiplexing (WSDM) optical access network
      architecture utilizing multicore fibers with advanced modulation formats. As a
      proof of concept, we experimentally demonstrated a WSDM optical access network
      with duplex transmission using our developed and fabricated multicore (7-core)
      fibers with 58.7km distance. As a cost-effective modulation scheme for access
      network, the optical OFDM-QPSK signal has been intensity modulated on the
      downstream transmission in the optical line terminal (OLT) and it was directly
      detected in the optical network unit (ONU) after MCF transmission. 10 wavelengths
      with 25GHz channel spacing from an optical comb generator are employed and each
      wavelength is loaded with 5Gb/s OFDM-QPSK signal. After amplification, power
      splitting, and fan-in multiplexer, 10-wavelength downstream signal was injected
      into six outer layer cores simultaneously and the aggregation downstream capacity
      reaches 300 Gb/s. -16 dBm sensitivity has been achieved for 3.8 * 10<sup>-3</sup>
      bit error ratio (BER) with 7% Forward Error Correction (FEC) limit for all
      wavelengths in every core. Upstream signal from ONU side has also been generated
      and the bidirectional transmission in the same core causes negligible performance
      degradation to the downstream signal. As a universal platform for wired/wireless
      data access, our proposed architecture provides additional dimension for high
      speed mobile signal transmission and we hence demonstrated an upstream delivery
      of 20Gb/s per wavelength with QPSK modulation formats using the inner core of MCF
      emulating a mobile backhaul service. The IQ modulated data was coherently
      detected in the OLT side. -19 dBm sensitivity has been achieved under the FEC
      limit and more than 18 dB power budget is guaranteed. 

PMID- 25969195
TI  - High-average-power operation of a pulsed Raman fiber amplifier at 1686 nm.
AB  - We report on high-average-power operation of a pulsed Raman fiber amplifier at
      ~1686 nm which cannot be covered by rare-earth-doped fiber lasers. The Raman
      fiber amplifier was pumped by a home-made 1565.2 nm Q-switched Er,Yb fiber laser
      and worked at a repetition frequency of 184 kHz. With 0.8 km Raman fiber, 4.4 W
      of average output power at the 1st order Stokes wavelength of 1686.5 nm was
      obtained for launched pump power of 16.2 W, corresponding to an optical-to
      optical conversion efficiency of 27.2%. Further increasing the pump power, high
      order Stokes waves grew gradually, resulting in a total output power of 6.7 W at
      the 19.2 W launched pump power. 

PMID- 25969196
TI  - High-speed high-precision and ultralong-range complex spectral domain dimensional
      metrology.
AB  - A precise, nondestructive dimensional metrological system is crucial to
      manufacturing and packaging of multi-component optical system. To this end, an
      orthogonal dispersive spectrometer based complex spectral domain interferometric
      system for high-speed high-precision and ultralong-range dimensional metrology is
      developed. An improved complex method based on actual spectral phase shift is
      proposed to achieve ultrahigh suppression of artifacts. Suppression ratios of 80
      dB for DC and 60 dB for mirror images are realized, the highest ratios among
      existing complex methods. To ensure high-precision in distance determination, an
      averaged spectral phase measurement algorithm is adopted. A precision of 60 nm
      within a measurement range of 200 mm without axial movement of the sample is
      demonstrated. The measurement range is readily extendable if axial movement of
      the sample and range cascading are involved. The system holds potential
      applications in various areas for real-time nondestructive testing and
      evaluation. 

PMID- 25969197
TI  - Optically pumped GaN vertical cavity surface emitting laser with high index
      contrast nanoporous distributed Bragg reflector.
AB  - Laser operation of a GaN vertical cavity surface emitting laser (VCSEL) is
      demonstrated under optical pumping with a nanoporous distributed Bragg reflector
      (DBR). High reflectivity, approaching 100%, is obtained due to the high index
      contrast of the nanoporous DBR. The VCSEL system exhibits low threshold power
      density due to the formation of high Q-factor cavity, which shows the potential
      of nanoporous medium for optical devices. 

PMID- 25969198
TI  - Compact bending sensor based on a fiber Bragg grating in an abrupt biconical
      taper.
AB  - We propose and experimentally demonstrate a compact bending sensor. The head of
      the sensor is only 0.8 mm in length, and consists of an abrupt biconical fiber
      taper formed using a conventional fusion splicer, in which a fiber Bragg grating
      (FBG) is inscribed using a femtosecond laser. The biconical taper incorporating
      the FBG can couple light from the cladding to the backward-propagating core mode,
      which realizes an interferometer in reflection-mode. Bending of the structure can
      be detected from the contrast change of interference fringes. A configuration to
      measure curvature is investigated to demonstrate the sensing characteristics. The
      temperature cross-sensitivity of the sensor is studied, and the results
      demonstrate that it is insensitive to temperature. 

PMID- 25969199
TI  - Stable and wavelength-locked Q-switched narrow-linewidth Er:YAG laser at 1645 nm.
AB  - A stable and wavelength-locked Q-switched narrow-linewidth Er:YAG laser with
      compact cavity structure, utilizing a volume Bragg grating (VBG) as a wavelength
      selector and a pump input mirror simultaneously, is reported. It yields high
      energy nanosecond pulse with pulse duration of 185 ns and pulse energy of 1.36 mJ
      at 1 kHz pulse repetition frequency for incident pump power of 21.6 W. The
      central wavelength of the Er:YAG laser is locked at 1645.3 nm with a spectral 3
      dB linewidth of less than 0.08 nm, which coincides to the methane (CH4)
      absorption-line. The output has near diffraction-limited beam quality with M2
      parameter of 1.08. Our work may provide an inroad for developing more
      miniaturized space-based integrated path differential absorption (IDPA) lidar
      transmitter.

PMID- 25969200
TI  - Modification of light transmission channels by inhomogeneous absorption in random
      media.
AB  - Optical absorption is omnipresent and often distributed non-uniformly in space.
      We present a numerical study on the effects of inhomogeneous absorption on
      transmission eigenchannels of light in highly scattering media. In the weak
      absorption regime, the spatial profile of a transmission channel remains similar
      to that without absorption, and the effect of inhomogeneous absorption can be
      stronger or weaker than homogeneous absorption depending on the spatial overlap
      of the localized absorbing region with the field intensity maximum of the
      channel. In the strong absorption regime, the high transmission channels redirect
      the energy flows to circumvent the absorbing regions to minimize loss. The
      attenuation of high transmission channels by inhomogeneous absorption is lower
      than that by homogeneous absorption, regardless of the location of the absorbing
      region. The statistical distribution of transmission eigenvalues in the former
      becomes broader than that in the latter, due to a longer tail at high
      transmission. The maximum enhancement factor of total transmission increases with
      absorption, eventually exceeds that without absorption. 

PMID- 25969201
TI  - Mechanism of Q-spoiling in deformed optical microcavities.
AB  - It was reported that Q spoiling in a chaotic microcavity is caused by chaos [PRL,
      75, 2682 (1995)] and chaos-assisted tunneling [Nature 385, 45 (1997)]. However,
      even when a cavity is slightly deformed not to exhibit a broad chaotic region in
      phase space, high Q modes are spoiled. We find that Q spoiling in this region is
      caused by the transition of a whispering gallery mode (WGM) to a scarred
      resonance when a WGM interacts with its pair quasi-normal mode through an avoided
      resonance crossing. We prove that this transition induces Q spoiling in a
      quadrupole dielectric microcavity by showing that Q factors obtained from the
      Husimi functions depending on resonance deformation during the transition agree
      well with those obtained from the complex eigenvalues. 

PMID- 25969202
TI  - Near field stacking of zone plates for reduction of their effective zone period.
AB  - Here we analyze the potential of a new fabrication method for high resolution
      zone plates with high aspect ratios based on near field stacking of frequency
      doubled atomic layer deposited (ALD) zone plates. The proposed method enables
      reduction of the effective zone period by a factor of four with two zone plate
      layers compared to the initial e-beam lithography exposed outermost zone period.
      It also overcomes the problem that very small zone widths with high aspect ratios
      have to be fabricated for high-resolution hard X-ray microscopy. Using rigorous
      coupled wave theory, we have analyzed the diffraction behavior of these near
      field stacked zone plates and investigated strategies to optimize fabrication
      parameters to compensate for separation of stacked zone plates. The calculations
      performed for 8 keV photon energy and effective outermost zone widths of 28 nm
      and 15 nm predict diffraction efficiencies >= 20% suggesting that such optics
      could find widespread practical applications. 

PMID- 25969203
TI  - Distributed measurement of high electric current by means of polarimetric optical
      fiber sensor.
AB  - A novel distributed optical fiber sensor for spatially resolved monitoring of
      high direct electric current is proposed and analyzed. The sensor exploits
      Faraday rotation and is based on the polarization analysis of the Rayleigh
      backscattered light. Preliminary laboratory tests, performed on a section of
      electric cable for currents up to 2.5 kA, have confirmed the viability of the
      method. 

PMID- 25969204
TI  - Full three-dimensional power flow analysis of single-emitter-plasmonic
      nanoantenna system.
AB  - We present a full three-dimensional (3D) power flow analysis of an emitter
      nanoantenna system. A conventional analysis, based on the total Poynting vector,
      calculates only the coupling strength in terms of the Purcell enhancement. For a
      better understanding of the emitter-nanoantenna system, not only the Purcell
      enhancement but also complete information on the energy transfer channels is
      necessary. The separation of the pure scattering and emitter output Poynting
      vectors enables the quantification of the individual energy transfer channels.
      Employing the finite-difference time-domain method (FDTD), we examine a nanodisk
      antenna that supports the bright dipole and dark quadrupole resonance modes for
      which the power flow characteristics are completely distinct, and we analyze the
      power flow enhancements to the energy transfer channels with respect to the
      wavelength, polarization, and position of the emitter coupled to the antenna. The
      3D power flow analysis reveals how the constructive or destructive interference
      between the emitter and the antenna resonance mode affects the power flow
      enhancements and the far-field radiation pattern. Our proposed power flow
      analysis should play a critical role in characterizing the emitter-antenna system
      and customizing its energy transfer properties for desired applications. 

PMID- 25969205
TI  - Patch-primitive driven compressive ghost imaging.
AB  - Ghost imaging has rapidly developed for about two decades and attracted wide
      attention from different research fields. However, the practical applications of
      ghost imaging are still largely limited, by its low reconstruction quality and
      large required measurements. Inspired by the fact that the natural image patches
      usually exhibit simple structures, and these structures share common primitives,
      we propose a patch-primitive driven reconstruction approach to raise the quality
      of ghost imaging. Specifically, we resort to a statistical learning strategy by
      representing each image patch with sparse coefficients upon an over-complete
      dictionary. The dictionary is composed of various primitives learned from a large
      number of image patches from a natural image database. By introducing a linear
      mapping between non-overlapping image patches and the whole image, we incorporate
      the above local prior into the convex optimization framework of compressive ghost
      imaging. Experiments demonstrate that our method could obtain better
      reconstruction from the same amount of measurements, and thus reduce the number
      of requisite measurements for achieving satisfying imaging quality. 

PMID- 25969206
TI  - Mid-infrared Fourier-transform spectroscopy with a high-brilliance tunable laser
      source: investigating sample areas down to 5 MUm diameter.
AB  - We demonstrate highly sensitive infrared spectroscopy of sample volumes close to
      the diffraction limit by coupling a femtosecond fiber-feedback optical parametric
      oscillator (OPO) to a conventional Fourier-transform infrared (FTIR)
      spectrometer. The high brilliance and long-term stable infrared radiation with
      1e(2)-bandwidths up to 125 nm is easily tunable between 1.4 MUm and 4.2 MUm at 43
      MHz repetition rate and thus enables rapid and low-noise infrared spectroscopy.
      We demonstrate this by measuring typical molecular vibrations in the range of 3
      MUm. Combined with surface-enhanced infrared spectroscopy, where the confined
      electromagnetic near-fields of resonantly excited metal nanoparticles are
      employed to enhance molecular vibrations, we realize the spectroscopic detection
      of a molecular monolayer of octadecanethiol. In comparison to conventional light
      sources and synchrotron radiation, our compact table-top OPO system features a
      significantly improved performance making it highly suitable for rapid analysis
      of minute amounts of molecular species in life science and medicine laboratories.

PMID- 25969207
TI  - An ultrathin terahertz quarter-wave plate using planar babinet-inverted
      metasurface.
AB  - Metamaterials promise an exotic approach to artificially manipulate the
      polarization state of electromagnetic waves and boost the design of polarimetric
      devices for sensitive detection, imaging and wireless communication. Here, we
      present the design and experimental demonstration of an ultrathin (0.29lambda)
      terahertz quarter-wave plate based on planar babinet-inverted metasurface. The
      quarter-wave plate consisting of arrays of asymmetric cross apertures reveals a
      high transmission of 0.545 with 90 degrees phase delay at 0.870 THz. The
      calculated ellipticity indicates a high degree of polarization conversion from
      linear to circular polarization. With respect to different incident polarization
      angles, left-handed circular polarized light, right-handed circular polarized
      light and elliptically polarized light can be created by this novel design. An
      analytical model is applied to describe transmitted amplitude, phase delay and
      ellipticitiy, which are in good agreement with the measured and simulated
      results. The planar babinet-inverted metasurface with the analytical model opens
      up avenues for new functional terahertz devices design. 

PMID- 25969208
TI  - Magnetically controllable wavelength-division-multiplexing fiber coupler.
AB  - In this paper, a magnetically controllable wavelength-division-multiplexing (WDM)
      fiber coupler has been proposed and experimentally demonstrated. A theoretical
      model has been established to analyze the influences of the weak as well as
      strong couplings to the wavelength tunability of this coupler. Experimental
      results show that the operation wavelength tunability of the proposed WDM coupler
      could be fulfilled for an applied magnetic field intensity range of 0 Oe to 500
      Oe, and particularly it possesses high operation performances within the magnetic
      field intensity ranging from 25 Oe to 125 Oe when additional transmission loss
      and isolation are both considered. Within this range, the two selected channels
      show the wavelength tunability of 0.05 nm/Oe and 0.0744 nm/Oe, respectively, and
      the isolation between the two branches is higher than 24.089 dB. Owing to its
      high isolation, good splitting ratio stability, and high wavelength tunability,
      the proposed controllable WDM coupler is anticipated to find potential
      applications in such fields as fiber laser, fiber sensing and fiber-optic
      communications. Moreover, the fiber coupler integrated with the magnetic fluid
      would be valuable for the design of magnetically controllable mode-division
      multiplexing devices. 

PMID- 25969209
TI  - Mode-locked laser operation of Indium-modified Yb:KY(WO4)2 single crystal.
AB  - We report the first pulsed laser operation of an Indium-modified Yb:KY(WO4)2
      crystal. Indium incorporation enlarges the broadening of the Yb3+ optical bands,
      reduces crystal lattice parameters and increases n(p) refractive index. A
      KY0.8In0.07Yb0.13(WO4)2 crystal pumped at 981 nm with a Ti-sapphire laser in a
      SESAM modulated resonator produces at 300 K self-starting and stable mode
      locking. The shortest laser pulses achieved were centred at lambda = 1041.1 nm,
      have a duration of 96 fs with average power of 134 mW and repetition rate of
      103.5 MHz (1.3 nJ/pulse).

PMID- 25969210
TI  - Tunable fractional-order photonic differentiator based on the inverse Raman
      scattering in a silicon microring resonator.
AB  - A novel photonic fractional-order temporal differentiator is proposed based on
      the inverse Raman scattering (IRS) in the side-coupled silicon microring
      resonator. By controlling the power of the pump light-wave, the intracavity loss
      is adjusted and the coupling state of the microring resonator can be changed, so
      the continuously tunable differentiation order is achieved. The influences of
      input pulse width on the differentiation order and the output deviation are
      discussed. Due to the narrow bandwidth of IRS in silicon, the intracavity loss
      can be adjusted on a specific resonance while keeping the adjacent resonances
      undisturbed. It can be expected that the proposed scheme has the potential to
      realize different differentiation orders simultaneously at different resonant
      wavelengths. 

PMID- 25969211
TI  - Low-loss and fabrication tolerant silicon mode-order converters based on novel
      compact tapers.
AB  - We propose large bandwidth and high fabrication-tolerance mode-order converters
      on the silicon-on-insulator platform based on novel compact tapers structures.
      Each of the converters is in a single waveguide. Designs of different symmetries
      with and without breaking the parities between odd and even modes are
      illustrated. The fabrication tolerances of the devices are also investigated. The
      simulation results show that high conversion efficiencies can be readily achieved
      over a wavelength range from 1520 nm to 1580 nm for all of the proposed devices.
      The average conversion efficiencies of TE1-to-TE0, TE2-to-TE0, TE3-to-TE0, TE2-to
      TE1, TE3-to-TE1, and TE3-to-TE2 converters are -0.061 dB, -0.052 dB, -0.11 dB, 
      0.119 dB, -0.168 dB, and -0.154 dB, respectively. The conversion efficiencies
      have negligible degradations under normal width and thickness deviations. 

PMID- 25969212
TI  - Low-loss titanium dioxide waveguides and resonators using a dielectric lift-off
      fabrication process.
AB  - We present a bi-layer lift-off fabrication approach to create low-loss amorphous
      titanium dioxide (TiO2) integrated optical waveguides and resonators for visible
      and near-infrared applications. This approach achieves single-mode waveguide
      losses as low as 7.5 dB/cm around 633 nm and 1.2 dB/cm around 1550 nm, a factor
      of 4 improvement over previous reports, without the need to optimize etching
      conditions. Depositing a secondary 260-nm TiO2 layer can reduce losses further,
      with the optimized process yielding micro-ring resonators with loaded quality
      factors as high as 1.5 * 10(5) around 1550 nm and 1.6*10(5) around 780 nm. These
      losses render our TiO2 devices suitable for visible and telecommunications
      applications; in addition, the simplicity of this lift-off approach is broadly
      applicable to other novel material platforms, particularly using near-visible
      wavelengths.

PMID- 25969213
TI  - A highly linear superconducting bolometer for quantitative THz Fourier transform
      spectroscopy.
AB  - A superconducting transition edge sensor (TES) bolometer operating in the
      spectral range from 0.1 THz to 3 THz was designed. It is especially intended for
      Fourier transform spectroscopy and features a higher dynamic range and a highly
      linear response at a similar response compared to commercially available silicon
      composite bolometers. The design is based on a thin film metal mesh absorber, a
      superconducting thermistor and Si3N4 membrane technology. A prototype was set up,
      characterized and successfully used in first applications.

PMID- 25969214
TI  - Broadband nonlinear optical response in multi-layer black phosphorus: an emerging
      infrared and mid-infrared optical material.
AB  - Black phosphorous (BP), the most thermodynamically stable allotrope of
      phosphorus, is a high-mobility layered semiconductor with direct band-gap
      determined by the number of layers from 0.3 eV (bulk) to 2.0 eV (single layer).
      Therefore, BP is considered as a natural candidate for broadband optical
      applications, particularly in the infrared (IR) and mid-IR part of the spectrum.
      The strong light-matter interaction, narrow direct band-gap, and wide range of
      tunable optical response make BP as a promising nonlinear optical material,
      particularly with great potentials for infrared and mid-infrared opto
      electronics. Herein, we experimentally verified its broadband and enhanced
      saturable absorption of multi-layer BP (with a thickness of ~10 nm) by wide-band
      Z-scan measurement technique, and anticipated that multi-layer BPs could be
      developed as another new type of two-dimensional saturable absorber with
      operation bandwidth ranging from the visible (400 nm) towards mid-IR (at least
      1930 nm). Our results might suggest that ultra-thin multi-layer BP films could be
      potentially developed as broadband ultra-fast photonics devices, such as passive
      Q-switcher, mode-locker, optical switcher etc. 

PMID- 25969215
TI  - Suppressed ionic effect and low-frequency texture transitions in a cholesteric
      liquid crystal doped with graphene nanoplatelets.
AB  - We focus on investigating the dielectric behaviors and the low-frequency texture
      transitions in a cholesteric liquid crystal (CLC) doped with graphene
      nanoplatelets (GNPs) by means of dielectric spectroscopy and measurements of
      electro-optical responses. The experimental results indicate that incorporating
      GNPs at a content of 0.5 wt% into the CLC leads to significant suppression of
      ionic behaviors, as manifested by the reduction in ionic density, diffusivity,
      and relaxation frequency. In addition, the electro-optical properties of the GNP
      doped CLC cell show the lowered operation voltage for the switching from the
      planar to focal conic state and the absence of the low-frequency focal-conic-to
      uniform-lying-helix texture transition. Such results are attributable to the
      effects of GNPs as nuclei in the CLC medium, giving rise to the repression of the
      ionic and electrohydrodynamic effects. 

PMID- 25969216
TI  - 1590-nm-pumped passively Q-switched thulium all-fiber laser at 1900 nm.
AB  - We propose and demonstrate a passively Q-switched 1900-nm thulium all-fiber laser
      using the mode-field-area mismatch method. A thulium fiber laser was core-pumped
      at 1590 nm and saturable-absorber Q-switched at 1900 nm through the use of a
      thulium saturable absorber fiber that had a relatively smaller mode field area
      than the gain medium. Sequential pulsing with a pulse energy of 12 MUJ and a
      pulse duration of 160 ns was obtained. The pulse repetition rate was increased
      linearly with the applied pump power. With a pump power of 4.5 W, an average
      output power of 0.61 W and a pulse repetition rate of 50.7 kHz were achieved. 

PMID- 25969217
TI  - Efficiency enhancement of organic light-emitting devices due to a localized
      surface plasmonic resonance effect of poly(4-butylphenyl-diphenyl
      amine):dodecanethiol functionalized Au nanocomposites.
AB  - Organic light-emitting devices (OLEDs) were fabricated utilizing a poly(4
      butylphenyl-diphenyl-amine) (poly-TPD):dodecanethiol functionalized Au (DDT-Au)
      nanocomposite (NC) layer to enhance their current efficiency. The
      photoluminescence intensity of the poly-TPD:DDT-Au NC film at 514 nm was
      significantly increased, being about 1.3 times that of the poly-TPD film due to
      the coupling between the excitons in the emitting layer and the localized surface
      plasmonic resonance of the DDT-Au nanoparticles. The current efficiency of the
      green OLEDs with a poly-TPD:DDT-Au NC layer at 1000 cd/m2 was 3.1 cd/A larger
      than that with a poly-TPD layer, resulting in an enhanced out-coupling efficiency
      due to the coupling effect.

PMID- 25969218
TI  - Impact of local oscillator frequency noise on coherent optical systems with
      electronic dispersion compensation.
AB  - A theoretical investigation of the equalization-enhanced phase noise (EEPN) and
      its mitigation is presented. We show with a frequency domain analysis that the
      EEPN results from the non-linear inter-mixing between the sidebands of the
      dispersed signal and the noise sidebands of the local oscillator. It is further
      shown and validated with system simulations that the transmission penalty is
      mainly due to the slow optical frequency fluctuations of the local oscillator.
      Hence, elimination of the frequency noise below a certain cut-off frequency
      significantly reduces the transmission penalty, even when frequency noise would
      otherwise cause an error floor. The required cut-off frequency increases linearly
      with the white frequency noise level and hence the linewidth of the local
      oscillator laser, but is virtually independent of the symbol rate and the
      accumulated dispersion. 

PMID- 25969219
TI  - Optical frequency standard using acetylene-filled hollow-core photonic crystal
      fibers.
AB  - Gas-filled hollow-core photonic crystal fibers are used to stabilize a fiber
      laser to the 13C2H2 P(16) (nu1+nu3) transition at 1542 nm using saturated
      absorption. Four hollow-core fibers with different crystal structure are compared
      in terms of long term lock-point repeatability and fractional frequency
      instability. The locked fiber laser shows a fractional frequency instability
      below 4 * 10(-12) for averaging time up to 10(4) s. The lock-point repeatability
      over more than 1 year is 1.3 * 10(-11), corresponding to a standard deviation of
      2.5 kHz. A complete experimental investigation of the light-matter interaction
      between the spatial modes excited in the fibers and the frequency of the locked
      laser is presented. A simple theoretical model that explains the interaction is
      also developed.

PMID- 25969220
TI  - Dynamic range improvement in analog photonic link by intermodulation-compensation
      receiver.
AB  - In this paper, a novel intermodulation-compensation optical receiver based on the
      bias-modulated photo detector (PD) is proposed and demonstrated to eliminate the
      third-order intermodulation (IMD3) for the intensity-modulation direct-detection
      (IMDD) analog photonic link. We directly extract the key nonlinear distortion
      from the distorted optical intensity by a low-pass optical receiver, which is
      used to modulate the home-made, high-speed PD with bias modulation. Inside the
      high speed PD, the distorted radio frequency (RF) band is mixed with the above
      extracted baseband signal, and the IMD3 elimination can be achieved. Our proposal
      is theoretically analyzed, and the performance of the bias-modulated PD is
      experimentally demonstrated. Spurious-free dynamic range (SFDR) of 123.4 dB
      within 1-Hz bandwidth is obtained with 18.1 dB improvement. A low-biased Mach
      Zehnder modulator (MZM) is used, keeping a simple transmitter with an improved
      link gain. The proposed post linearization requires no digital processing,
      avoiding the high quantization noise. 

PMID- 25969221
TI  - Temporal power spectrum of irradiance fluctuations for a Gaussian-beam wave
      propagating through non-Kolmogorov turbulence.
AB  - In the past decades, both the increasing experimental evidence and some results
      of theoretical investigation on non-Kolmogorov turbulence have been reported.
      This has prompted the study of optical propagation in non-Kolmogorov atmospheric
      turbulence. In this paper, based on the thin phase screen model and a non
      Kolmogorov power spectrum which owns a generalized power law instead of standard
      Kolmogorov power law value 11/3 and a generalized amplitude factor instead of
      constant value 0.033, the temporal power spectrum of irradiance fluctuations for
      a Gaussian-beam wave is derived in the weak fluctuation regime for a horizontal
      path. The analytic expressions are obtained and then used to analyze the
      influence of spectral power law variations on the temporal power spectrum of
      irradiance fluctuations. 

PMID- 25969222
TI  - Large step-phase measurement by a reduced-phase triple-illumination
      interferometer.
AB  - We present a reduced-phase triple-illumination interferometer (RPTII) as a novel
      single-shot technique to increase the precision of dual-illumination optical
      phase unwrapping techniques. The technique employs two measurement ranges to
      record both low-precision unwrapped and high-precision wrapped phases. To unwrap
      the high-precision phase, a hierarchical optical phase unwrapping algorithm is
      used with the low-precision unwrapped phase. The feasibility of this technique is
      demonstrated by measuring a stepped object with a height 2100 times greater than
      the wavelength of the source. The phase is reconstructed without applying any
      numerical unwrapping algorithms, and its noise level is decreased by a factor of
      ten. 

PMID- 25969223
TI  - Multi-octave spectral beam combiner on ultra-broadband photonic integrated
      circuit platform.
AB  - We present the design of a novel platform that is able to combine optical
      frequency bands spanning 4.2 octaves from ultraviolet to mid-wave infrared into a
      single, low M2 output waveguide. We present the design and realization of a key
      component in this platform that combines the wavelength bands of 350 nm - 1500 nm
      and 1500 nm - 6500 nm with demonstrated efficiency greater than 90% in near
      infrared and mid-wave infrared. The multi-octave spectral beam combiner concept
      is realized using an integrated platform with silicon nitride waveguides and
      silicon waveguides. Simulated bandwidth is shown to be over four octaves, and
      measured bandwidth is shown over two octaves, limited by the availability of
      sources.

PMID- 25969224
TI  - Optical signal to noise ratio monitoring using variable phase difference phase
      portrait with software synchronization.
AB  - In this paper, a novel optical signal to noise ratio (OSNR) monitoring method
      using 2-dimension (2-D) phase portrait is proposed and demonstrated, which is
      generated by using a single low-speed sampling channel with software
      synchronization technique. Moreover, variable phase difference is proposed to
      generate the X-Y pairs, which increases the tolerance of synchronization accuracy
      significantly. This method is a cost effective solution with simple system setup.

PMID- 25969225
TI  - Modal interference in spiky nanoshells.
AB  - Near-field enhancement of the electric field by metallic nanostructures is
      important in non-linear optical applications such as surface enhanced Raman
      scattering. One approach to producing strong localization of the electric field
      is to couple a dark, non-radiating plasmonic mode with a broad dipolar resonator
      that is detectable in the far-field. However, characterizing or predicting the
      degree of the coupling between these modes for a complicated nanostructure can be
      quite challenging. Here we develop a robust method to solve the T-matrix, the
      matrix that predicts the scattered electric fields of the incident light, based
      on finite-difference time-domain (FDTD) simulations and least square fitting
      algorithms. This method allows us to simultaneously calculate the T-matrix for a
      broad spectral range. Using this method, the coupling between the electric dipole
      and quadrupole modes of spiky nanoshells is evaluated. It is shown that the built
      in disorder in the structure of these nanoshells allows for coupling between the
      dipole modes of various orientations as well as coupling between the dipole and
      the quadrupole modes. A coupling strength of about 5% between these modes can
      explain the apparent interference features observed in the single particle
      scattering spectrum. This effect is experimentally verified by single particle
      backscattering measurements of spiky nanoshells. The modal interference in
      disordered spiky nanoshells can explain the origin of the spectrally broad
      quadrupole resonances that result in strong Quadrupole Enhanced Raman Scattering
      (QERS) in these nanoparticles. 

PMID- 25969226
TI  - Topology-optimized multiple-disk resonators obtained using level set expression
      incorporating surface effects.
AB  - Topology-optimized designs of multiple-disk resonators are presented using level
      set expression that incorporates surface effects. Effects from total internal
      reflection at the surfaces of the dielectric disks are precisely simulated by
      modeling clearly defined dielectric boundaries during topology optimization. The
      electric field intensity in optimal resonators increases to more than four and a
      half times the initial intensity in a resonant state, whereas in some cases the Q
      factor increases by three and a half times that for the initial state. Wavelength
      scale link structures between neighboring disks improve the performance of the
      multiple-disk resonators. 

PMID- 25969227
TI  - Lifetime investigation of single nitrogen vacancy centres in nanodiamonds.
AB  - In this paper we investigate at room temperature the excited state lifetime of
      single NV(-)/NV0 in nanodiamonds at a variety of excitation wavelengths from 510
      to 570 nm. The average lifetimes of 25 nanodiamonds with similar sizes exhibit
      constant values over the entire investigated spectral window. We conclude that
      the variation observed can be attributed to the specific nanodiamonds. Therefore
      it is sample dependent, rather than related to the photo-physical properties of
      the defects. Our study is relevant for the potential use of nanodiamonds
      containing NV in application where the lifetime is used for sensing the local
      nano-environment.

PMID- 25969228
TI  - Stimulated emission at 288 nm from silicon-doped AlGaN-based multiple-quantum
      well laser.
AB  - We demonstrated stimulated emission at 288 nm from a silicon-doped AlGaN-based
      multiple-quantum-well (MQW) ultraviolet (UV) laser grown on sapphire. The optical
      pumping threshold energy density of the UV laser was 64 mJ/cm2, while lasing
      behavior was not observed in undoped AlGaN MQWs. This means silicon doping could
      effectively reduce the lasing threshold of UV lasers, and the mechanism was
      studied showing that the silicon-doped AlGaN MQWs had a 41% higher internal
      quantum efficiency (IQE) compared with the undoped one. The transmission electron
      microscopy characterization showed that silicon doping explicitly improved the
      crystallographic quality of MQWs. Calculation of the polarization charge in the
      MQWs further revealed that the advantage of better structure quality outweighed
      the reduction of internal polarization field by Si doping for the IQE enhancement
      and successful stimulated emission.

PMID- 25969229
TI  - Removal of noise and radial lens distortion during calibration of computer vision
      systems.
AB  - The calibration of computer vision systems that contain the camera and the
      projector usually utilizes markers of the well-designed patterns to calculate the
      system parameters. Undesirably, the noise and radial distortion exist
      universally, which decreases the calibration accuracy and consequently decreases
      the measurement accuracy of the related technology. In this paper, a method is
      proposed to remove the noise and radial distortion by registering the captured
      pattern with an ideal pattern. After the optimal modeled pattern is obtained by
      registration, the degree of freedom of the total calibration markers is reduced
      to one and both the noise and radial distortion are removed successfully. The
      accuracy improvement in a structured light scanning system is over 10(24) order
      of magnitude in the sense of mean square errors. Most importantly, the proposed
      method can be readily adopted by the computer vision techniques that use
      projectors or cameras.

PMID- 25969230
TI  - Quantitative study of the quadratic magneto-optical Kerr effects in Fe films.
AB  - We present a rotating field method to separate the linear and quadratic magneto
      optical Kerr effects (LMOKE and QMOKE) in Fe/GaAs(001) films. The LMOKE is
      isotropic in crystal orientation, while the QMOKE has both isotropic and
      anisotropic contributions. The experimental observation is well explained by
      Yeh's 4*4 matrix formalism. We also report the incident angle and the thickness
      dependences of the LMOKE and QMOKE, and extract the material's index of
      refraction n and the magneto-optical coupling constant K and G. The study gives a
      full description of the Kerr effect in Fe films, and the proposed method can be
      applied to other magneto-optical coupling systems. 

PMID- 25969231
TI  - Real-time absolute frequency measurement of continuous-wave terahertz radiation
      based on dual terahertz combs of photocarriers with different frequency spacings.
AB  - Real-time measurement of the absolute frequency of continuous-wave terahertz (CW
      THz) radiation is required for characterization and frequency calibration of
      practical CW-THz sources. We proposed a method for real-time monitoring of the
      absolute frequency of CW-THz radiation involving temporally parallel, i.e.,
      simultaneous, measurement of two pairs of beat frequencies and laser repetition
      frequencies based on dual THz combs of photocarriers (PC-THz combs) with
      different frequency spacings. To demonstrate the method, THz-comb-referenced
      spectrum analyzers were constructed with a dual configuration based on dual
      femtosecond lasers. Regardless of the presence or absence of frequency control in
      the PC-THz combs, a frequency precision of 10(-11) was achieved at a measurement
      rate of 100 Hz. Furthermore, large fluctuation of the CW-THz frequencies,
      crossing several modes of the PC-THz combs, was correctly monitored in real time.
      The proposed method will be a powerful tool for the research and development of
      practical CW-THz sources, and other applications.

PMID- 25969232
TI  - Two-stage crossed beam cooling with 6Li and 133Cs atoms in microgravity.
AB  - Applying the direct simulation Monte Carlo (DSMC) method developed for ultracold
      Bose-Fermi mixture gases research, we study the sympathetic cooling process of
      6Li and 133Cs atoms in a crossed optical dipole trap. The obstacles to producing
      6Li Fermi degenerate gas via direct sympathetic cooling with 133Cs are also
      analyzed, by which we find that the side-effect of the gravity is one of the main
      obstacles. Based on the dynamic nature of 6Li and 133Cs atoms, we suggest a two
      stage cooling process with two pairs of crossed beams in microgravity
      environment. According to our simulations, the temperature of 6Li atoms can be
      cooled to T = 29.5 pK and T/TF = 0.59 with several thousand atoms, which propose
      a novel way to get ultracold fermion atoms with quantum degeneracy near pico
      Kelvin.

PMID- 25969233
TI  - Continuous-wave operation up to 20  degrees C of deep-ridge npn-InGaAsP/InP
      multiple quantum well transistor laser emitting at 1.5-MUm wavelength.
AB  - We report continuous-wave (CW) operation up to 20  degrees C of 1.5-MUm
      wavelength npn-InGaAsP/InP multiple quantum well (MQW) transistor laser (TL) with
      a deep-ridge structure. With CW laser emission, the common emitter current gain
      of the device can be over 3.5, which is significantly larger than those of the
      previously reported long wavelength TLs. It is found that at low base current,
      the laser operation occurs on the first excited state of the MQWs. At high base
      current, however, the device shows stimulated emissions on the ground state
      transition. The trend is contrary to what has been observed in the GaAs based TLs
      and is explained by the change of carrier flow at different base currents. 

PMID- 25969234
TI  - Quantitative differential phase contrast imaging in an LED array microscope.
AB  - Illumination-based differential phase contrast (DPC) is a phase imaging method
      that uses a pair of images with asymmetric illumination patterns. Distinct from
      coherent techniques, DPC relies on spatially partially coherent light, providing
      2* better lateral resolution, better optical sectioning and immunity to speckle
      noise. In this paper, we derive the 2D weak object transfer function (WOTF) and
      develop a quantitative phase reconstruction method that is robust to noise. The
      effect of spatial coherence is studied experimentally, and multiple-angle DPC is
      shown to provide improved frequency coverage for more stable phase recovery. Our
      method uses an LED array microscope to achieve real-time (10 Hz) quantitative
      phase imaging with in vitro live cell samples. 

PMID- 25969235
TI  - Design and modeling of an ultra-compact 2x2 nanomechanical plasmonic switch.
AB  - A 2x2 Mach-Zehnder optical switch design with a footprint of 0.5 MUm x 2.5 MUm
      using nanomechanical gap plasmon phase modulators [Nat. Photonics 9(4),267
      273(2015)] is presented. The extremely small footprint and modest optical loss
      are enabled by the strong phase modulation of gap plasmons in a mechanically
      actuated 17 nm air gap. Frequency-domain finite-element modeling at operating
      wavelength 780 nm shows that the insertion loss is <= 8.5 dB, the extinction
      ratio is > 25 dB, and crosstalk for all ports is > 24 dB. A design optimization
      approach and its dependence on geometrical parameters are discussed. 

PMID- 25969236
TI  - 40 Gb/s CAP32 short reach transmission over 80 km single mode fiber.
AB  - We present a method to mitigate the chromatic dispersion (CD)-induced power
      fading effect (PFE) in high-speed and short-reach carrier-less amplitude and
      phase (CAP) systems using the degenerate four-wave mixing (DFWM) effect and a
      decision feedback equalizer (DFE). Theoretical and numerical investigations
      reveal that DFWM components produced by the interaction between the main carrier
      and the signal sideband help to mitigate PFE in direct detection systems. By
      optimizing the launch power, a maximum reach of 60 km in single mode fiber (SMF-e
      + ) at 1530nm is experimentally demonstrated for a 40 Gbit/s CAP32 system. In
      addition, we study the performance of a decision feedback equalizer (DFE) and a
      traditional linear equalizer (LE) in a channel with non-flat in-band frequency
      response. The superior PFE tolerance of DFE is experimentally validated, and
      thereby, the maximum reach is extended to 80 km. To the best of our knowledge,
      this is the twice the longest transmission distance reported so far for a single
      carrier 40 Gbit/s CAP system around 1550 nm. 

PMID- 25969237
TI  - Trap-level-engineered common red layer for fabricating red, green, and blue
      subpixels of full-color organic light-emitting diode displays.
AB  - We report a novel strategy to reduce one fine metal mask (FMM) step in a full
      color organic light-emitting diode (OLED) display by introducing a common red
      layer (CRL) which replaces a hole transporting layer (HTL) with the same
      thickness of a red phosphorescent dye-doped layer. Because the dopant in the HTL
      acts as a hole trap, careful trap-level engineering is required for achieving
      efficient green and blue emission from the emitting layer while minimizing the
      red emission from the CRL. We investigated the characteristics of OLEDs depending
      on hole trap levels of the CRL with five different organic HTLs, and demonstrated
      efficient red, green and blue (RGB) emitting devices using the CRL. The
      electroluminescence spectrum of the devices with the CRL is nearly identical with
      those of the devices without the CRL. These results open up the possibility of
      simplified fabrication of practical full-color OLED displays with the reduced FMM
      steps, resulting in lower manufacturing cost. 

PMID- 25969238
TI  - Broadband field-resolved terahertz detection via laser induced air plasma with
      controlled optical bias.
AB  - We report a robust method of coherent detection of broadband THz pulses using
      terahertz induced second-harmonic (TISH) generation in a laser induced air plasma
      together with a controlled second harmonic optical bias. We discuss a role of the
      bias field and its phase in the process of coherent detection. Phase-matching
      considerations subject to plasma dispersion are also examined. 

PMID- 25969239
TI  - Giant enhancement of two photon induced luminescence in metal nanostructure.
AB  - We experimentally demonstrate a drastic increase in the rate of radiative process
      of a nanoscale physical system with implementation of the three physical effects:
      (1) the size effect, (2) plasmon resonance and (3) the optical Tamm state. As an
      example of a nanoscale physical system, we choose a single nanohole in Au film
      when the nanohole is embedded in a photonic crystal of a specific type that
      maintains an optical Tamm state and as a radiative process - a nonlinear
      photoluminescence. The efficiency of the nonlinear photoluminescence is increased
      by more than 10(7) times in compare to a bulk material.

PMID- 25969240
TI  - WS2 as a saturable absorber for ultrafast photonic applications of mode-locked
      and Q-switched lasers.
AB  - Two-dimensional (2D) nanomaterials, especially the transition metal sulfide
      semiconductors, have drawn great interests due to their potential applications in
      viable photonic and optoelectronic devices. In this work, 2D tungsten disulfide
      (WS2) based saturable absorber (SA) for ultrafast photonic applications was
      demonstrated. WS2 nanosheets were prepared using liquid-phase exfoliation method
      and embedded in polyvinyl alcohol (PVA) thin film for the practical usage.
      Saturable absorption was discovered in the WS2-PVA SA at the telecommunication
      wavelength near 1550 nm. By incorporating WS2-PVA SA into a fiber laser cavity,
      both stable mode locking operation and Q-switching operation were achieved. In
      the mode locking operation, the laser obtained femtosecond output pulse width and
      high spectral purity in the radio frequency spectrum. In the Q-switching
      operation, the laser had tunable repetition rate and output pulse energy of a few
      tens of nano joule. Our findings suggest that few-layer WS2 nanosheets embedded
      in PVA thin film are promising nonlinear optical materials for ultrafast photonic
      applications as a mode locker or Q-switcher.

PMID- 25969241
TI  - Small divergence substrate emitting quantum cascade laser by subwavelength
      metallic grating.
AB  - Metallic periodic structure in subwavelength scale offers an exciting way to
      couple light into surface plasmons (SPs), thus manipulating the properties of
      near-field optics. We show that subwavelength metallic grating (SMG) defined on
      the substrate side of substrate emitting quantum cascade lasers enables far-field
      improvement in mid-infrared spectrum. The SMG is designed to tailor the
      interaction of SPs with single mode transverse magnetic light. The experiment
      results are in good agreement with the simulated model. A far-field full width at
      half maximum (FWHM) divergence angle of 3.9  degrees  in the direction
      perpendicular to the laser waveguide layers is obtained, improved by a factor of
      8.5 compared with traditional surface emitting device. 

PMID- 25969242
TI  - High-speed modulation in ladder transitions in Rb atoms using high-pressure
      buffer gas.
AB  - Modulators using atomic systems are often limited in speed by the rate of
      spontaneous emission. One approach for overcoming this limit is to make use of a
      buffer gas such as Ethane, which causes rapid fine structure mixing of the P(1/2)
      and P(3/2) states, and broadens the absorption spectra of the D1 and D2 lines in
      alkali atoms. Employing this effect, we show that one can achieve high speed
      modulation using ladder transitions in Rubidium. We demonstrate a 100-fold
      increase, due to the addition of the buffer gas, in the modulation bandwidth
      using the 5S-5P-5D cascade system. The observed bandwidth of ~200 MHz is within a
      factor of 2.5 of the upper bound of ~0.51 GHz for the system used, and is limited
      by various practical constraints in our experiment. We also present numerical
      simulations for the system and predict that a much higher modulation speed should
      be achievable under suitable conditions. In combination with a tapered nano fiber
      or a SiN waveguide, it has the potential to be used for high-speed, low-power all
      optical modulation.

PMID- 25969243
TI  - Correlation singularities in a partially coherent electromagnetic beam with
      initially radial polarization.
AB  - We have investigated the correlation singularities, coherence vortices of two
      point correlation function in a partially coherent vector beam with initially
      radial polarization, i.e., partially coherent radially polarized (PCRP) beam. It
      is found that these singularities generally occur during free space propagation.
      Analytical formulae for characterizing the dynamics of the correlation
      singularities on propagation are derived. The influence of the spatial coherence
      length of the beam on the evolution properties of the correlation singularities
      and the conditions for creation and annihilation of the correlation singularities
      during propagation have been studied in detail based on the derived formulae.
      Some interesting results are illustrated. These correlation singularities have
      implication for interference experiments with a PCRP beam. 

PMID- 25969244
TI  - Parity-time symmetric coupled microresonators with a dispersive gain/loss.
AB  - The paper reports on the coupling of Parity-Time (PT)-symmetric whispering
      gallery resonators with realistic material and gain/loss models. Response of the
      PT system is analyzed for the case of low and high material and gain dispersion,
      and also for two practical scenarios when the pump frequency is not aligned with
      the resonant frequency of the desired whispering gallery mode and when there is
      imbalance in the gain/loss profile. The results show that the presence of
      dispersion and frequency misalignment causes skewness in frequency bifurcation
      and significant reduction of the PT breaking point, respectively. Finally, we
      demonstrate a lasing mode operation which occurs due to an early PT-breaking by
      increasing loss in a PT system with unbalanced gain and loss. 

PMID- 25969245
TI  - Three-pathway electromagnetically induced transparency in coupled-cavity
      optomechanical system.
AB  - Recently Qu and Agarwal [Phys. Rev. A 22, 031802 (2013)] found a three-pathway
      electromagnetically induced absorption (TEIA) phenomenon within a mechanically
      coupled two-cavity system, where there exist a sharp EIA dip in the broad
      electromagnetically induced transparency peak in the transmission spectrum. In
      this work, we study the response of a probe light in a pair of directly coupled
      microcavities with one mechanical mode. We find that in addition to the sharp
      TEIA dip within a broad EIT window as found by Qu and Agarwal, three-pathway
      electromagnetically induced transparency (TEIT) within the broad EIT window could
      also exist under certain conditions. We give explicit physical explanations and
      detailed calculations. Our results provide a method for controlling transition
      between TEIA and TEIT in coupled optomechanical systems, and reveal the multiple
      pathways interference is versatile for controlling light.

PMID- 25969246
TI  - Polarization control in flexible interference lithography for nano-patterning of
      different photonic structures with optimized contrast.
AB  - Half-wave plates were introduced into an interference-lithography scheme
      consisting of three fibers that were arranged into a rectangular triangle. Such a
      flexible and compact geometry allows convenient tuning of the polarizations of
      both the UV laser source and each branch arm. This not only enables optimization
      of the contrast of the produced photonic structures with expected square
      lattices, but also multiplies the nano-patterning functions of a fixed design of
      fiber-based interference lithography. The patterns of the photonic structures can
      be thus tuned simply by rotating a half-wave plate. 

PMID- 25969247
TI  - Ultrasensitive temperature fiber sensor based on Fabry-Perot interferometer
      assisted with iron V-groove.
AB  - A fiber extrinsic Fabry-Perot interferometer (EFPI) assisted with iron V-groove
      for temperature measurement is proposed and investigated by means of both
      numerical simulation and experiment for the first time to our best knowledge. The
      main temperature sensing component is acted by the iron V-groove whose
      coefficient of linear thermal expansion (CLTE) is much higher than that of the
      silica glass. Two fibers are stuck to the V-groove with two glued points,
      respectively. Maximum sensitivity of 260.7 nm/ degrees C, which is the highest
      value for a fiber interferometric sensor up to now, has been achieved
      experimentally. It is worth noting that the temperature sensitivity of this
      sensor can be improved limitlessly via implementing a smaller gap size of the
      EFPI, longer distance between the two glued points or material with higher CLTE
      of the V-groove, theoretically. 

PMID- 25969248
TI  - Enhancement of magneto-optical Kerr effect by surface plasmons in trilayer
      structure consisting of double-layer dielectrics and ferromagnetic metal.
AB  - Giant enhancement of the magneto-optical Kerr effect (MOKE) by surface plasmon
      polaritons (SPPs) is theoretically shown in a trilayer structure consisting of
      double-layer dielectrics and a ferromagnetic metal (Al2O3/SiO2/Fe). We calculated
      the resonant enhancement of the transverse MOKE (TMOKE) and polar MOKE (PMOKE)
      using the attenuated total reflection (ATR) configuration with the transfer
      matrix method using a 4 * 4 scattering matrix. At a specific film thickness of
      the low-index SiO2 layer, where confinement of the SPPs on the Fe surface becomes
      close to the cutoff condition, the incident light from the Al2O3 couples with the
      SPPs at the SiO2/Fe boundary most efficiently, resulting in resonant enhancement
      of the MOKE at an incident angle corresponding to the wave vector of the SPPs.
      The calculated PMOKE showed orthogonal transformation (90 degrees -rotation) and
      almost full-orbed deformation (44 degrees -ellipticity) of the polarization, and
      the TMOKE showed a change in reflectance of about 34 dB upon magnetization
      reversal.

PMID- 25969249
TI  - Classification of coherent vortices creation and distance of topological charge
      conservation in non-Kolmogorov atmospheric turbulence.
AB  - The analytical expressions for the cross-spectral density function of partially
      coherent sinh-Gaussian (ShG) vortex beams propagating through free space and non
      Kolmogorov atmospheric turbulence are derived, and used to study the
      classification of coherent vortices creation and distance of topological charge
      conservation. With the increment of the general structure constant and the waist
      width, as well as the decrement of the general exponent, the inner scale of
      turbulence and spatial correlation length, the distance of topological charge
      conservation will decrease, whereas the outer scale of turbulence and the Sh-part
      parameter have no effect on the distance of topological charge conservation.
      According to the creation, the coherent vortices are grouped into three classes:
      the first is the inherent coherent vortices of the vortex beams, the second is
      created by the vortex beams when propagating through free space, and the third is
      created by the atmospheric turbulence inducing the vortex beams. 

PMID- 25969250
TI  - Elimination of polarization degeneracy in circularly symmetric bianisotropic
      waveguides: a decoupled case.
AB  - Mode properties of circularly symmetric waveguides with one special type of
      bianisotropy are studied using finite element approach. We find that the
      polarization degeneracy in circularly symmetric waveguides can be eliminated, by
      introducing intrinsic crossing coupling between electric and magnetic moments in
      the constituent units of the waveguide media. Breaking the polarization
      degeneracy in high order mode groups is also confirmed numerically. With the
      bianisotropic parameters chosen in this work, the x and y-polarized modes remain
      decoupled. Typically, the y-polarized modes remain completely unchanged, while
      the x-polarized modes are turned into leaky modes that are lossy along
      propagation direction. A perturbation model from coupled mode theory is developed
      to explain the results and shows excellent agreement. Such asymmetric behavior
      between different polarizations might be feasible and useful for developing
      compact polarizers in terahertz or mid-infrared regime. 

PMID- 25969251
TI  - Accurate control of chromaticity and spectra by feedback phosphor-coating.
AB  - The chromaticity coordinates and spectra of phosphor-converted LEDs are
      demonstrated to be well controlled in this study. Through the feedback coating
      method of stacked yellow, green, and red phosphor layers, the color rendering
      index (CRI), correlated color temperature (CCT), and spectra are determined to
      match precisely the desired target. In addition, the reabsorption effect is
      strongly influenced by the order of stacked phosphor layers and the selected
      excitation wavelength of phosphors. The degree of reabsorption will modify the
      original spectra and cause a mismatch between the experimental measurement and
      the simulation based on the linear superposition of blue light and phosphor
      emitted light. This feedback coating method offers an easy approach towards
      optimized spectra, which can offer the highest luminous efficacy of radiation
      with excellent color-rendering properties. 

PMID- 25969252
TI  - Permanently reconfigured metamaterials due to terahertz induced mass transfer of
      gold.
AB  - We present a new technique for permanent metamaterial reconfiguration via
      optically induced mass transfer of gold. This mass transfer, which can be
      explained by field-emission induced electromigration, causes a geometric change
      in the metamaterial sample. Since a metamaterial's electromagnetic response is
      dictated by its geometry, this structural change massively alters the
      metamaterial's behavior. We show this by optically forming a conducting pathway
      between two closely spaced dipole antennas, thereby changing the resonance
      frequency by a factor of two. After discussing the physics of the process, we
      conclude by presenting an optical fuse that can be used as a sacrificial element
      to protect sensitive components, demonstrating the applicability of optically
      induced mass transfer for device design. 

PMID- 25969253
TI  - Multi-users network model and the corresponding networking scheme for indoor VLC
      systems.
AB  - Recently, the visible light communication (VLC) based on LEDs has attracted much
      attention. In order to realize multi-users indoor VLC system based on the hybrid
      full-duplex, we design a kind of illumination/communication terminal and present
      the corresponding network model in this paper. We propose a multi-access scheme,
      which can avoid the access collision and network congestion. Meanwhile, we
      present a method to establish the link between users and expound the routing
      strategy of information forwarding. Besides, we evaluate the network performance
      by numerical simulations in aspects of access collision probability, throughput,
      access time and link establishment time. The results show that the proposed multi
      access scheme and routing strategy are feasible for indoor VLC system. 

PMID- 25969254
TI  - Spatio-temporal optical random number generator.
AB  - We present a first random number generator (RNG) which simultaneously uses
      independent spatial and temporal quantum randomness contained in an optical
      system. Availability of the two independent sources of entropy makes the RNG
      resilient to hardware failure and signal injection attacks. We show that the
      deviation from randomness of the generated numbers can be estimated quickly from
      simple measurements thus eliminating the need for usual time-consuming
      statistical testing of the output data. As a confirmation it is demonstrated that
      generated numbers pass NIST Statistical test suite. 

PMID- 25969255
TI  - THz saturable absorption in turbostratic multilayer graphene on silicon carbide.
AB  - We investigated the room-temperature Terahertz (THz) response as saturable
      absorber of turbostratic multilayer graphene grown on the carbon-face of silicon
      carbide. By employing an open-aperture z-scan method and a 2.9 THz quantum
      cascade laser as source, a 10% enhancement of transparency is observed. The
      saturation intensity is several W/cm2, mostly attributed to the Pauli blocking
      effect in the intrinsic graphene layers. A visible increase of the modulation
      depth as a function of the number of graphene sheets was recorded as consequence
      of the low nonsaturable losses. The latter in turn revealed that crystalline
      disorder is the main limitation to larger modulations, demonstrating that the THz
      nonlinear absorption properties of turbostratic graphene can be engineered via a
      proper control of the crystalline disorder and the layers number.

PMID- 25969256
TI  - Spatio-temporal modification of femtosecond focal spot under tight focusing
      condition.
AB  - The focusing property of a focal spot of a femtosecond laser pulse is presented
      under tight focusing conditions (below f-number of 1). The spatial and temporal
      intensity distributions of a focused electric field are calculated by vector
      diffraction integrals and coherent superposition method. The validity of the
      calculation method is examined by comparing the intensity distribution obtained
      under a high f-number condition to that obtained with the fast Fourier transform
      method that assumes the scalar paraxial approximation. The spatial and temporal
      modifications under tight focusing conditions are described for a focused
      femtosecond laser pulse. The calculation results show that a peak intensity of
      about 2.5x10(24) W/cm2 can be achievable by tightly focusing a 12-fs, 10 PW laser
      pulse with a f/0.5 parabolic optic. The precise information on intensity
      distributions of a femtosecond focal spot obtained under a tight focusing
      condition will be crucial in assessing a focused intensity and in describing the
      motion of charged particles under an extremely strong electric field in ultra
      relativistic and/or relativistic laser matter-interaction studies.

PMID- 25969257
TI  - Ultrabroad terahertz bandpass filter by hyperbolic metamaterial waveguide.
AB  - We propose and demonstrate an ultrabroad terahertz (THz) bandpass filter (BPF) by
      integrating two different-sized tapered hyperbolic metamaterial (HMM) waveguides,
      each of which has wide but different absorption and transmission bands, into a
      unit cell. With proper structural design of each HMM waveguide to control the
      absorption and transmission bands, we numerically demonstrate the designed BPF is
      capable of operating with a broad passband in the THz domain. A typical TM
      polarized HMM BPF has a peak transmission of 37% at 3.3 THz with the passband
      bandwidth of 2.2 THz ranging from 2.97 to 5.17 THz. The co-designed three
      dimensional HMM BPF also shows the capability of operating with independence to
      the polarization of incident light because of the structural symmetry and has
      sharp bandedge transitions of 22.6 and 17.6 dB/THz to the stop bands,
      respectively. The presented results here hold great promise for developing
      practical THz BPF with various applications in THz field. 

PMID- 25969258
TI  - Asymmetric transmission and reflection spectra of FBG in single-multi-single mode
      fiber structure.
AB  - We give a comprehensive theoretical analysis and simulation of a FBG in single
      multi-single mode fiber structure (FBG-in-SMS), based on the coupled mode
      analysis and the mode interference analysis. This enables us to explain the
      experimental observations, its asymmetric transmission and reflection spectra
      with the similar temperature responses near the spectral range of Bragg
      wavelengths. The transmission spectrum shift during FBG written-in process is
      observed and discussed. The analysis results are useful in the design of the SMS
      structure based sensors and filters. 

PMID- 25969259
TI  - Monolithic high-index contrast grating: a material independent high-reflectance
      VCSEL mirror.
AB  - In this paper we present an extensive theoretical and numerical analysis of
      monolithic high-index contrast grating, facilitating simple manufacture of
      compact mirrors for very broad spectrum of vertical-cavity surface-emitting
      lasers (VCSELs) emitting from ultraviolet to mid-infrared. We provide the
      theoretical background explaining the phenomenon of high reflectance in
      monolithic subwavelength gratings. In addition, by using a three-dimensional,
      fully vectorial optical model, verified by comparison with the experiment, we
      investigate the optimal parameters of high-index contrast grating enabling more
      than 99.99% reflectance in the diversity of photonic materials and in the broad
      range of wavelengths. 

PMID- 25969260
TI  - Transmission properties of slanted annular aperture arrays. Giant energy
      deviation over sub-wavelength distance.
AB  - This paper is devoted to the study of the transmission properties of Slanted
      Annular Aperture Arrays made in perfectly conducting metal. More precisely, we
      consider the transmission based on the excitation of the cutoff-less guided mode,
      namely the TEM mode. We numerically and analytically demonstrate some intrinsic
      properties of the structure showing a transmission coefficient of at least 50% of
      an unpolarized incident beam independently of the illumination configuration
      (angle and plane of incidence). The central symmetry exhibited by the structure
      is analytically exploited to demonstrate the existence of a polarization state
      for which all the incident energy is transmitted through the sub-wavelength
      apertures when the eigenmode is excited, whatever are the illumination and the
      geometrical parameters. For this state of polarization, the laminar flow of the
      energy through the structure can exhibit giant deviation over very small
      distances. An example of energy flow deviation of 220 degrees  per wavelength is
      presented for illustration. The results presented in this paper could be
      considered as an important contribution to the understanding of the enhanced
      transmission phenomenon based on the excitation of guided modes. 

PMID- 25969261
TI  - Dense arrays of millimeter-sized glass lenses fabricated at wafer-level.
AB  - This paper presents the study of a fabrication technique of lenses arrays based
      on the reflow of glass inside cylindrical silicon cavities. Lenses whose sizes
      are out of the microfabrication standards are considered. In particular, the case
      of high fill factor arrays is discussed in detail since the proximity between
      lenses generates undesired effects. These effects, not experienced when lenses
      are sufficiently separated so that they can be considered as single items, are
      corrected by properly designing the silicon cavities. Complete topographic as
      well as optical characterizations are reported. The compatibility of materials
      with Micro-Opto-Electromechanical Systems (MOEMS) integration processes makes
      this technology attractive for the miniaturization of inspection systems,
      especially those devoted to imaging. 

PMID- 25969262
TI  - Linear optics, Raman scattering, and spin noise spectroscopy.
AB  - Spin noise spectroscopy (SNS) is a new method for studying magnetic resonance and
      spin dynamics that has gained, in the last several years, a considerable
      popularity. The method is based on measuring magnetization noise of a paramagnet
      using the Faraday rotation technique. In strong contrast with methods of
      nonlinear optics, the spectroscopy of spin noise is considered to be essentially
      nonperturbative. At the same time, presently, it became clear that the SNS, as an
      optical technique, demonstrates abilities lying far beyond the bounds of
      conventional linear optics. Specifically, the SNS allows one to penetrate inside
      an inhomogeneously broadened absorption band and to determine its homogeneous
      width, to realize a sort of pump-probe spectroscopy without any optical
      nonlinearity, to probe a bulk inhomogeneous medium by focal point of a probe
      beam, etc. This may seem especially puzzling when taken into account that SNS can
      be considered just as a version of Raman spectroscopy, which is known to be
      deprived of such abilities. Understanding of these paradoxical features of SNS
      technique is required for the present-day applications of SNS and its further
      development. In this paper, we present a general analysis of this apparent
      inconsistency from the viewpoint of distinction between spectroscopy of the light
      intensity and of the light field and provide its resolution. 

PMID- 25969264
TI  - GaSb-based mid infrared photonic crystal surface emitting lasers.
AB  - We demonstrated for the first time above room temperature (RT) GaSb-based mid
      infrared photonic crystal surface emitting lasers (PCSELs). The lasers, under
      optical pumping, emitted at lambda(lasing)~2.3MUm, had a temperature insensitive
      line width of 0.3nm, and a threshold power density (P(th)) ~0.3KW/cm2 at RT. Type
      I InGaAsSb quantum wells were used as the active region, and the photonic
      crystal, a square lattice, was fabricated on the surface to provide optical
      feedback for laser operation and light coupling for surface emission. The PCSELs
      were operated at temperatures up to 350K with a small wavelength shift rate of
      0.21 nm/K. The PCSELs with different air hole depth were studied. The effect of
      the etched depth on the laser performance was also investigated using numerical
      simulation based on the coupled-wave theory. Both the laser wavelength and the
      threshold power decrease as the depth of the PC becomes larger. The calculated
      results agree well with the experimental findings.

PMID- 25969263
TI  - Nonlinear phase noise mitigation in phase-sensitive amplified transmission
      systems.
AB  - We investigate the impact of in-line amplifier noise in transmission systems
      amplified by two-mode phase-sensitive amplifiers (PSAs) and present the first
      experimental demonstration of nonlinear phase noise (NLPN) mitigation in a
      modulation format independent PSA-amplified transmission system. The NLPN
      mitigation capability is attributed to the correlated noise on the signal and
      idler waves at the input of the transmission span. We study a single-span system
      with noise loading in the transmitter but the results are expected to be
      applicable also in multi-span systems. The experimental investigation is
      supported by numerical simulations showing excellent agreement with the
      experiments. In addition to demonstrating NLPN mitigation we also present a
      record high sensitivity receiver, enabled by low-noise PSA-amplification,
      requiring only 4.1 photons per bit to obtain a bit error ratio (BER) of 1 * 10(
      3) with 10 GBd quadrature phase-shift keying (QPSK) data.

PMID- 25969265
TI  - Determining the orientation of transition moments and depolarization by
      fluorescence polarizing angle spectrum.
AB  - In this paper, fluorescence polarizing angle spectrum, combined with degree of
      polarization(DOP), is proposed to determine the spatial orientation of transition
      dipole moments (TDMs) and depolarization of chlorophyll in solution. It is found
      that, due to the oriented TDMs under polarized laser excitation, the projections
      of angle of polarization(AOP) and DOP on the three orthogonal planes are
      different from each other. Experiments demonstrate that we can acquire the
      spatial orientation by detecting the projections of AOP on two orthogonal planes
      (xOz and yOz). Meanwhile, The depolarization can also be determined by the DOP
      spectrums. The validity of this method has been verified by another projection on
      the xOy plane. 

PMID- 25969266
TI  - Exploiting the image of the surface reflectivity to measure refractive index
      profiling for various optical fibers.
AB  - A direct image method of surface reflectivities on a cleaved fiber end with a
      filtered halogen lamp and a TE-cooled CCD with high dynamic range is proposed to
      measure the multi-wavelength refractive index profiling (RIP). A polished black
      glass is used to be a reference standard for measuring the absolute reflectivity
      of the fiber end. With the developed calibration procedures, both the spatially
      dependent sensitivity and spectral responsivity of the CCD pixels can be
      eliminated to achieve the high spatial accuracy. Tested fiber is connected with a
      fiber terminator to prevent errors from the backside return light. With the
      present method, the RIP can be precisely measured for not only multi-mode fibers
      but also single-mode fibers. 

PMID- 25969267
TI  - Rounding corners of nano-square patches for multispectral plasmonic metamaterial
      absorbers.
AB  - Multispectral metamaterial absorbers based on metal-insulator-metal nano-square
      patch resonators are studied here. For a geometry consisting of perfectly nano
      square patches and vertical sidewalls, double resonances in the visible regime
      are observed due to simultaneous excitation of electric and magnetic plasmon
      modes. Although slightly modifying the sizes of the square patches makes the
      resonance wavelengths simply shift, rounding corners of the square patches
      results in emergence of a third resonance due to excitation of the circular
      cavity modes. Sidewall angle of the patches are also observed to affect the
      absorption spectra significantly. Peak absorption values for the triple resonance
      structures are strongly affected as the sidewall angle varies from 90 to 50
      degrees. Rounded corners and slanted sidewalls are typical imperfections for
      lithographically fabricated metamaterial structures. The presented results
      suggest that imperfections caused during fabrication of the top nano-structures
      must be taken into account when designing metamaterial absorbers. Furthermore, it
      is shown that these fabrication imperfections can be exploited for improving
      resonance properties and bandwidths of metamaterials for various potential
      applications such as solar energy harvesting, thermal emitters, surface enhanced
      spectroscopies and photodetection. 

PMID- 25969268
TI  - Sensitivity analysis and optimization method for the fabrication of one
      dimensional beam-splitting phase gratings.
AB  - A method to design one-dimensional beam-spitting phase gratings with low
      sensitivity to fabrication errors is described. The method optimizes the phase
      function of a grating by minimizing the integrated variance of the energy of each
      output beam over a range of fabrication errors. Numerical results for three 1x9
      beam splitting phase gratings are given. Two optimized gratings with low
      sensitivity to fabrication errors were compared with a grating designed for
      optimal efficiency. These three gratings were fabricated using gray-scale
      photolithography. The standard deviation of the 9 outgoing beam energies in the
      optimized gratings were 2.3 and 3.4 times lower than the optimal efficiency
      grating. 

PMID- 25969269
TI  - Parity-time-symmetry breaking in double-slab surface-plasmon-polariton
      waveguides.
AB  - We theoretically demonstrate spontaneous PT-symmetry breaking behavior of surface
      plasmon polaritons (SPP) in coupled double-slab (DS) waveguides. By virtue of a
      flat-top field at critical wavelength, the imaginary index of a DS-SPP mode can
      be controlled via changing the core thickness, while the real index is kept
      constant. Therefore, a waveguide coupler that consists of a pair of DS-SPP
      waveguides with different core thicknesses can represent a passive PT-symmetric
      system, which always maintains symmetry under a real potential. This set-up also
      represents a good opportunity to investigate the underlying physics of PT
      symmetry breaking in non-Hermitian Hamiltonian systems. 

PMID- 25969270
TI  - Stopping terahertz radiation without backscattering over a broad band.
AB  - We present an approach to completely stop terahertz radiation in an optical
      system with a gyroelectric semiconductor. This system is composed of guiding and
      stopping parts formed by the semiconductor with different cladding structures.
      Because the dispersion properties of surface magnetoplasmons (SMPs) in the
      semiconductor closely depend on its cladding structure, robust one-way SMPs
      sustained by the guiding part are prohibited in the stopping part, thereby
      stopping terahertz radiation without any backscattering. For incident continuous
      waves, trapped spots with strongly enhanced fields occur on a subwavelength
      scale. For incident pulses, the wave packets can be completely trapped and
      simultaneously compressed to subwavelength sizes. 

PMID- 25969271
TI  - Multispectral interference filter arrays with compensation of angular dependence
      or extended spectral range.
AB  - Thin film Fabry-Perot filter arrays with high selectivity can be realized with a
      single patterning step, generating a spatial modulation of the effective
      refractive index in the optical cavity. In this paper, we investigate the ability
      of this technology to address two applications in the field of image sensors.
      First, the spectral tuning may be used to compensate the blue-shift of the
      filters in oblique incidence, provided the filter array is located in an image
      plane of an optical system with higher field of view than aperture angle. The
      technique is analyzed for various types of filters and experimental evidence is
      shown with copper-dielectric infrared filters. Then, we propose a design of a
      multispectral filter array with an extended spectral range spanning the visible
      and near-infrared range, using a single set of materials and realizable on a
      single substrate. 

PMID- 25969272
TI  - LCD-based digital eyeglass for modulating spatial-angular information.
AB  - Using programmable aperture to modulate spatial-angular information of light
      field is well-known in computational photography and microscopy. Inspired by this
      concept, we report a digital eyeglass design that adaptively modulates light
      field entering human eyes. The main hardware includes a transparent liquid
      crystal display (LCD) and a mini-camera. The device analyzes the spatial-angular
      information of the camera image in real time and subsequently sends a command to
      form a certain pattern on the LCD. We show that, the eyeglass prototype can
      adaptively reduce light transmission from bright sources by ~80% and retain
      transparency to other dim objects meanwhile. One application of the reported
      device is to reduce discomforting glare caused by vehicle headlamps. To this end,
      we report the preliminary result of using the reported device in a road test. The
      reported device may also find applications in military operations (sniper scope),
      laser counter measure, STEM education, and enhancing visual contrast for visually
      impaired patients and elderly people with low vision. 

PMID- 25969273
TI  - 1.21 W passively mode-locked Tm:LuAG laser.
AB  - A watt-level output passively mode-locked Tm:LuAG bulk laser with an InGaAs
      semiconductor saturable absorber mirror (SESAM) is demonstrated for the first
      time. A maximum average output power of 1.21 W at 2022.9 nm has been achieved
      with a pulse duration of 38 ps and a repetition rate of 129.2 MHz. The results
      indicate the potential of Tm:LuAG crystals as candidate for realizing high power
      ultrafast lasers at 2 MUm. 

PMID- 25969274
TI  - Radiance transmittance measured at the ocean surface.
AB  - The radiance transmittance (Tr) is the ratio of the water-leaving radiance
      (Lw(0+)) to the sub-surface upwelling radiance (Lu(0-)), which is an important
      optical parameter for ocean optics and ocean color remote sensing. Historically,
      a constant value (~0.54) based on theoretical presumptions has been adopted for
      Tr and is widely used. This optical parameter, however, has never been measured
      in the aquatic environments. With a robust setup to measure both Lu(0-) and
      Lw(0+) simultaneously in the field, this study presents Tr in the zenith
      direction between 350 and 700 nm measured in a wide range of oceanic waters. It
      is found that the measured Tr values are generally consistent with the long
      standing theoretical value of 0.54, with mean relative difference less than 10%.
      In particular, the agreement within the spectral domain of 400-600 nm is found to
      be the best (with the averaged difference less than 5%). The largest difference
      is observed for wavelengths longer than 600 nm with the average difference less
      than 15%, which is related to the generally very small values in both Lu(0-) and
      Lw(0+) and rough environmental conditions. These results provide a validation of
      the setup for simultaneous measurements of upwelling radiance and water-leaving
      radiance and confidence in the theoretical Tr value used in ocean optics studies
      at least for oceanic waters.

PMID- 25969275
TI  - Pump RIN-induced impairments in unrepeatered transmission systems using
      distributed Raman amplifier.
AB  - High spectral efficiency modulation format based unrepeatered transmission
      systems using distributed Raman amplifier (DRA) have attracted much attention
      recently. To enhance the reach and optimize system performance, careful design of
      DRA is required based on the analysis of various types of impairments and their
      balance. In this paper, we study various pump RIN induced distortions on high
      spectral efficiency modulation formats. The vector theory of both 1st and higher
      order stimulated Raman scattering (SRS) effect using Jones-matrix formalism is
      presented. The pump RIN will induce three types of distortion on high spectral
      efficiency signals: intensity noise stemming from SRS, phase noise stemming from
      cross phase modulation (XPM), and polarization crosstalk stemming from cross
      polarization modulation (XPolM). An analytical model for the statistical property
      of relative phase noise (RPN) in higher order DRA without dealing with complex
      vector theory is derived. The impact of pump RIN induced impairments are analyzed
      in polarization-multiplexed (PM)-QPSK and PM-16QAM-based unrepeatered systems
      simulations using 1st, 2nd and 3rd-order forward pumped Raman amplifier. It is
      shown that at realistic RIN levels, negligible impairments will be induced to PM
      QPSK signals in 1st and 2nd order DRA, while non-negligible impairments will
      occur in 3rd order case. PM-16QAM signals suffer more penalties compared to PM
      QPSK with the same on-off gain where both 2nd and 3rd order DRA will cause non
      negligible performance degradations. We also investigate the performance of
      digital signal processing (DSP) algorithms to mitigate such impairments. 

PMID- 25969276
TI  - Spatially resolved electron energy loss spectroscopy of crescent-shaped plasmonic
      antennas.
AB  - We present a study of the optical properties of gold crescent-shaped antennas by
      means of electron energy loss spectroscopy. These structures exhibit particularly
      large field enhancement near their sharp features, support two non-degenerate
      dipolar (i.e., optically active) localised surface plasmon resonances, and are
      widely tunable by a choice of their shape and dimensions. Depending on the volume
      and shape, we resolved up to four plasmon resonances in metallic structures under
      study in the energy range of 0.8 - 2.4 eV: two dipolar and quadrupolar mode and a
      multimodal assembly. The boundary-element-method calculations reproduced the
      observed spectra and helped to identify the character of the resonances. The two
      lowest modes are of particular importance owing to their dipolar nature.
      Remarkably, they are both concentrated near the tips of the crescent, spectrally
      well resolved and their energies can be tuned between 0.8 - 1.5 eV and 1.2 - 2.0
      eV, respectively. As the lower spectral range covers the telecommunication
      wavelengths 1.30 and 1.55 MUm, we envisage the possible use of such
      nanostructures in infrared communication technology. 

PMID- 25969277
TI  - The first- and second-order temporal interference between thermal and laser
      light.
AB  - The first- and second-order temporal interference between two independent thermal
      and laser light beams is discussed by employing the superposition principle in
      Feynman's path integral theory. It is concluded that the first-order temporal
      interference pattern can not be observed by superposing two independent thermal
      and laser light beams, while the second-order temporal interference pattern can
      be observed in the same condition. These predictions are experimentally verified
      by employing pseudothermal light to simulate thermal light. The relationship
      between the indistinguishability of alternatives and photons is analyzed. The
      conclusions are helpful to understand the interference of different kinds of
      light and the difference between the coherence properties of thermal and laser
      light. 

PMID- 25969278
TI  - Raman-induced temporal condensed matter physics in gas-filled photonic crystal
      fibers.
AB  - Raman effect in gases can generate an extremely long-living wave of coherence
      that can lead to the establishment of an almost perfect temporal periodic
      variation of the medium refractive index. We show theoretically and numerically
      that the equations, regulate the pulse propagation in hollow-core photonic
      crystal fibers filled by Raman-active gas, are exactly identical to a classical
      problem in quantum condensed matter physics - but with the role of space and time
      reversed - namely an electron in a periodic potential subject to a constant
      electric field. We are therefore able to infer the existence of Wannier-Stark
      ladders, Bloch oscillations, and Zener tunneling, phenomena that are normally
      associated with condensed matter physics, using purely optical means. 

PMID- 25969279
TI  - Pattern dependence in high-speed Q-modulated distributed feedback laser.
AB  - We investigate the pattern dependence in high speed Q-modulated distributed
      feedback laser based on its complete physical structure and material properties.
      The structure parameters of the gain section as well as the modulation and phase
      sections are all taken into account in the simulations based on an integrated
      traveling wave model. Using this model, we show that an example Q-modulated DFB
      laser can achieve an extinction ratio of 6.8dB with a jitter of 4.7ps and a peak
      intensity fluctuation of less than 15% for 40Gbps RZ modulation signal. The
      simulation method is proved very useful for the complex laser structure design
      and high speed performance optimization, as well as for providing physical
      insight of the operation mechanism. 

PMID- 25969280
TI  - Reference-less measurement of the transmission matrix of a highly scattering
      material using a DMD and phase retrieval techniques.
AB  - This paper investigates experimental means of measuring the transmission matrix
      (TM) of a highly scattering medium, with the simplest optical setup. Spatial
      light modulation is performed by a digital micromirror device (DMD), allowing
      high rates and high pixel counts but only binary amplitude modulation. On the
      sensor side, without a reference beam, the CCD camera provides only intensity
      measurements. Within this framework, this paper shows that the TM can still be
      retrieved, through signal processing techniques of phase retrieval. This is
      experimentally validated on three criteria : quality of prediction, distribution
      of singular values, and quality of focusing. 

PMID- 25969281
TI  - Spatial light modulator based color polarization imaging.
AB  - We describe a compressive snapshot color polarization imager that encodes
      spatial, spectral, and polarization information using a liquid crystal modulator.
      We experimentally show that polarization imaging is compressible by multiplexing
      polarization states and present the reconstruction results. This compressive
      camera captures the spatial distribution of four polarizations and three color
      channels. It achieves <0.027 degrees  spatial resolution, 10(3) average
      extinction ratio, and >30 PSNR.

PMID- 25969282
TI  - Demonstration of digital fronthaul over self-seeded WDM-PON in commercial LTE
      environment.
AB  - CPRI between BBU and RRU equipment is carried by self-seeded WDM-PON prototype
      system within commercial LTE end-to-end environment. Delay and jitter meets CPRI
      requirements while services demonstrated show the same performance as bare fiber.

PMID- 25969283
TI  - Mirrorless dye doped ionic liquid lasers.
AB  - The study of electromagnetic waves propagation in periodically structured
      dielectrics and the linear and nonlinear optical phenomena in disordered systems
      doped with gain media represent one of the most challenging and exciting
      scientific areas of the past decade. Lasing and Random Lasers (RL) are
      fascinating examples of topics that synergize multiple scattering of light and
      optical amplification and lately have been the subject of intense theoretical and
      experimental studies. In this manuscript we demonstrate laser action in a new
      category of materials, namely dye doped ionic liquids. Ionic liquids prove to be
      perfect candidates for building, as shown, a series of exotic boundaryless or
      confined compact laser systems. Lasing is presented in standard wedge cells,
      freely suspended ionic liquid films and droplets. The optical emission properties
      are investigated in terms of spectral analysis, below and above lasing energy
      threshold behavior, emission efficiency, far field spatial laser modes intensity
      profiling, temporal emission behavior etc. As demonstrated, these materials can
      be employed as optimal near future replacements of conventional flammable
      solvents in already available dye laser instruments. 

PMID- 25969284
TI  - Superradiant modes in resonant quasi-periodic double-period quantum wells.
AB  - This paper firstly proposes the existence of superradiant modes in resonant quasi
      periodic double-period quantum wells (QWs), which has not been observed from
      analyzing the structure factor by traditional methods. Using the gap map method,
      the reflection spectra under the relevant conditions show that there are dips in
      the middle and the linewidth grows linearly, despite the dips, as the number of
      QWs increases, which is a direct demonstration of superradiance. It is also found
      that the relevant conditions are divided into three regions, each of which has a
      different width of bandgaps. 

PMID- 25969285
TI  - Efficient approximations of dispersion relations in optical waveguides with
      varying refractive-index profiles.
AB  - In this paper we consider the problem of computing the eigen-modes for the
      varying refractive-index profile in an open waveguide. We first approximate the
      refractive-index by a piecewise polynomial of degree two, and the corresponding
      Sturm-Liouville problem (eigenvalue problem) of the Helmholtz operator in each
      layer can be solved analytically by the Kummer functions. Then, analytical
      approximate dispersion equations are established for both TE and TM cases.
      Furthermore, the approximate dispersion equations converge fast to the exact ones
      for the continuous refractive-index function as the maximum value of the
      subinterval sizes tends to zero. Suitable numerical methods, such as Muller's
      method or the chord secant method, may be applied to the dispersion relations to
      compute the eigenmodes. Numerical simulations show that our method is very
      practical and efficient for computing eigenmodes. 

PMID- 25969286
TI  - Directed assembly of gold nanowires on silicon via reorganization and
      simultaneous fusion of randomly distributed gold nanoparticles.
AB  - Laser-induced reorganization and simultaneous fusion of nanoparticles is
      introduced as a versatile concept for pattern formation on surfaces. The process
      takes advantage of a phenomenon called laser-induced periodic surface structures
      (LIPSS) which originates from periodically alternating photonic fringe patterns
      in the near-field of solids. Associated photonic fringe patterns are shown to
      reorganize randomly distributed gold nanoparticles on a silicon wafer into
      periodic gold nanostructures. Concomitant melting due to optical heating
      facilitates the formation of continuous structures such as periodic gold nanowire
      arrays. Generated patterns can be converted into secondary structures using
      directed assembly or self-organization. This includes for example the rotation of
      gold nanowire arrays by arbitrary angles or their fragmentation into arrays of
      aligned gold nanoparticles. 

PMID- 25969287
TI  - Germanium wrap-around photodetectors on Silicon photonics.
AB  - We present a novel waveguide coupling scheme where a germanium diode grown via
      rapid melt growth is wrapped around a silicon waveguide. A 4 fF PIN photodiode is
      demonstrated with 0.95 A/W responsivity at 1550 nm, 6 nA dark current, and nearly
      9 GHz bandwidth. Devices with shorter intrinsic region exhibit higher bandwidth
      (30 GHz) and slightly lower responsivity (0.7 A/W). An NPN phototransistor is
      also demonstrated using the same design with 14 GHz f(T).

PMID- 25969288
TI  - Study of a low-cost trimodal polymer waveguide for interferometric optical
      biosensors.
AB  - A novel evanescent wave biosensor based on modal interaction between the
      fundamental mode and the second order mode is proposed and numerically
      demonstrated. By taking advantage of their symmetries, it is possible to design a
      device where only the fundamental and the second order modes can propagate,
      without excitation of the first order mode. With this selection of modes it is
      possible to achieve a high sensitivity behavior in the biosensor configuration,
      due to the strong interaction between the evanescent field and the outer surface
      as compared to previous evanescent wave-based biosensor designs. 

PMID- 25969289
TI  - Backscattering peak of ice cloud particles.
AB  - At a wavelength corresponding to negligible electromagnetic absorption by ice,
      rigorous numerical simulations based on solving Maxwell's equations show a
      backscattering peak associated with the phase function of randomly oriented
      hexagonal ice crystals. The backscattering peak, which has important implications
      to the interpretation of lidar observations, exists in the cases of smooth
      regular, smooth irregular, and roughened hexagonal ice crystals. The
      backscattering peak width is inversely proportional to the size parameter. The
      theoretical prediction of the backscattering peak is consistent with
      observations. 

PMID- 25969290
TI  - Mutually modulated cross-gain modulation with a considerable modulation
      wavenumber-interaction length product.
AB  - An extended theory of the mutually modulated cross-gain modulation was developed
      to make it valid under considerable modulated wavenumber-interaction length
      product. Parametric analysis of the extended theory shows that, in the modulated
      probe beam out of the gain medium, the spectral sensitivity of the first harmonic
      wave is associated with its amplitude. The larger the sensitivity is, the smaller
      the amplitude will be. An effective method was provided to monitor and achieve
      high spectral sensitivity at a pre-selected frequency detuning in practice. The
      validity of the extended theory was confirmed by a sensing experiment in a piece
      of ~10-km fiber with 10 kHz modulation frequency, in which a fast light
      propagation with a sensitivity of 0.592 mrad/kHz was achieved. 

PMID- 25969291
TI  - Integrated source of broadband quadrature squeezed light.
AB  - An integrated silicon nitride resonator is proposed as an ultra-compact source of
      bright single-mode quadrature squeezed light at 850 nm. Optical properties of the
      device are investigated and tailored through numerical simulations, with
      particular attention paid to loss associated with interfacing the device. An
      asymmetric double layer stack waveguide geometry with inverse vertical tapers is
      proposed for efficient and robust fibre-chip coupling, yielding a simulated total
      loss of -0.75 dB/facet. We assess the feasibility of the device through a full
      quantum noise analysis and derive the output squeezing spectrum for intra-cavity
      pump self-phase modulation. Subject to standard material loss and detection
      efficiencies, we find that the device holds promises for generating substantial
      quantum noise squeezing over a bandwidth exceeding 1 GHz. In the low-propagation
      loss regime, approximately -6 dB squeezing is predicted for a pump power of only
      75 mW. 

PMID- 25969292
TI  - Quantifying noise in ultrafast laser sources and its effect on nonlinear
      applications.
AB  - Nonlinear optical applications depend on pulse duration and coherence of the
      laser pulses. Characterization of high-repetition rate pulsed laser sources can
      be complicated by their pulse-to-pulse instabilities. Here, we introduce and
      demonstrate experimentally a quantitative measurement that can be used to
      determine the pulse-to-pulse fidelity of ultrafast laser sources. Numerical
      simulations and experiments illustrate the effect of spectral phase and amplitude
      noise on second and third harmonic generation. 

PMID- 25969293
TI  - Experimental driven modelling of the color appearance of unrelated self-luminous
      stimuli: CAM15u.
AB  - Based on an extensive magnitude estimation experiment, a new color appearance
      model for unrelated self-luminous stimuli, CAM15u, has been designed. With the
      spectral radiance of the stimulus as unique input, the model predicts the
      brightness, hue, colorfulness, saturation and amount of white. The main features
      of the model are the use of the CIE 2006 cone fundamentals, the inclusion of an
      absolute brightness scale and a very simple calculation procedure. The CAM15u
      model performs much better than existing models and has been validated by a
      validation experiment. The model is applicable to unrelated self-luminous stimuli
      with an angular extent of 10 degrees  and a photopic, but non-glare-inducing,
      luminance level. 

PMID- 25969294
TI  - Two orthogonal carriers assisted 101-Gb/s dual-band DDO-OFDM transmission over
      320-km SSMF.
AB  - We propose a novel fading-free direct-detection optical orthogonal frequency
      division multiplexing (DDO-OFDM) scheme for 100-Gb/s medium-reach transmission.
      In the proposed scheme, we adopts two bands spaced at 100-GHz to accommodate the
      same complex-valued OFDM signal. However, the signals are coupled with a pair of
      orthogonal optical carriers. By doing so, real and imaginary parts of the complex
      valued OFDM signal can be recovered from the two bands, respectively. We also
      propose a cost-effective scheme to generate such DDO-OFDM signal using an optical
      90-degree hybrid and an optical I/Q modulator. The advantage of the proposed
      method is that it is fading-free, and the electrical spectral efficiency (SE) is
      doubled compared to traditional direct-detection method. Finally, we
      experimentally demonstrated a 101-Gb/s dual-band transmission over 320-km SSMF
      within only 30-GHz electrical bandwidth, which is highly competitive in both
      capacity and cost. 

PMID- 25969295
TI  - Improved performance of tunable single-mode laser array based on high-order
      slotted surface grating.
AB  - We present an improved design of a wavelength-tunable single-mode laser array
      based on a high order surface grating with non-uniformly spaced slots. The laser
      array consists of 12 slotted single-mode lasers. The fabricated device exhibits a
      quasi-continuous tuning range of more than 36 nm over the temperature range from
      10 degrees C - 45 degrees C covering the full C-band. All lasers in the array
      have stable single-mode operation with side mode suppression ratio of 50 dB due
      to the modified slot design. A spectral linewidth of less than 500 kHz was
      obtained for all channels in the array. 

PMID- 25969296
TI  - Demonstration of 12.2% wall plug efficiency in uncooled single mode external
      cavity tunable Si/III-V hybrid laser.
AB  - A Si/III-V hybrid laser has been a highly sought after device for energy
      efficient and cost-effective high-speed silicon photonics communication. We
      present a high wall-plug efficiency external-cavity hybrid laser created by
      integrating an independently optimized SOI ring reflector and a III-V gain chip.
      In our demonstration, the uncooled integrated laser achieved a waveguide-coupled
      wall-plug efficiency of 12.2% at room temperature with an optical output power of
      ~10 mW. The laser operated single-mode near 1550 nm with a linewidth of 0.22 pm.
      This is a tunable light source with 8 nm wavelength tuning range. A proof-of
      concept laser wavelength stabilization technique has also been demonstrated.
      Using a simple feedback loop, we achieved mode-hop-free operation in a packaged
      external-cavity hybrid laser as bias current was varied by 60mA. 

PMID- 25969297
TI  - Double Dirac cones in two-dimensional dielectric photonic crystals.
AB  - By exploiting the accidental degeneracy of the doubly-degenerate dipolar and
      quadrupolar modes, we show that a two-dimensional dielectric photonic crystal
      (PC) can exhibit the double Dirac cone dispersion relation at the Gamma point.
      Using a perturbation method and group theory, we demonstrate that the double cone
      is composed of two identical and overlapping Dirac cones with predictable linear
      slopes, and the linearity of the dispersion is guaranteed by the spatial symmetry
      of the Bloch eigenstates. Numerical simulations including wave-front shaping,
      unidirectional transmission and perfect tunneling show that the corresponding PC
      structure can be characterized by a zero effective refractive index. 

PMID- 25969298
TI  - Broadband photonic microwave phase shifter based on controlling two RF modulation
      sidebands via a Fourier-domain optical processor.
AB  - An all-optical photonic microwave phase shifter that can realize a continuous 360
      degrees  phase shift over a wide frequency range is presented. It is based on the
      new concept of controlling the amplitude and phase of the two RF modulation
      sidebands via a Fourier-domain optical processor. The operating frequency range
      of the phase shifter is largely increased compared to the previously reported
      Fourier-domain optical processor based phase shifter that uses only one RF
      modulation sideband. This is due to the extension of the lower RF operating
      frequency by designing the amplitude and phase of one of the RF modulation
      sidebands while the other sideband is designed to realize the required RF signal
      phase shift. The two-sideband amplitude-and-phase-control based photonic
      microwave phase shifter has a simple structure as it only requires a single laser
      source, a phase modulator, a Fourier-domain optical processor and a single
      photodetector. Investigation on the bandwidth limitation problem in the
      conventional Fourier-domain optical processor based phase shifter is presented.
      Comparisons between the measured phase shifter output RF amplitude and phase
      responses with theory, which show excellent agreement, are also presented for the
      first time. Experimental results demonstrate the full -180 degrees  to + 180
      degrees  phase shift with little RF signal amplitude variation of less than 3 dB
      and with a phase deviation of less than 4 degrees  over a 7.5 GHz to 26.5 GHz
      frequency range, and the phase shifter exhibits a long term stable performance. 

PMID- 25969299
TI  - 60-GHz optical/wireless MIMO system integrated with optical subcarrier
      multiplexing and 2x2 wireless communication.
AB  - This paper proposes a 2x2 MIMO OFDM Radio-over-Fiber scheme based on optical
      subcarrier multiplexing and 60-GHz MIMO wireless transmission. We also
      schematically investigated the principle of optical subcarrier multiplexing,
      which is based on a dual-parallel Mach-Zehnder modulator (DP-MZM). In our
      simulation result, combining two MIMO OFDM signals to drive DP-MZM gives rise to
      the PAPR augmentation of less than 0.4 dB, which mitigates nonlinear distortion.
      Moreover, we applied a Levin-Campello bit-loading algorithm to compensate for the
      uneven frequency responses in the V-band. The resulting system achieves OFDM
      signal rates of 61.5-Gbits/s with BER of 10(-3) over 25-km SMF transmission
      followed by 3-m wireless transmission.

PMID- 25969300
TI  - Field-widened Michelson interferometer for spectral discrimination in high
      spectral-resolution lidar: theoretical framework.
AB  - A field-widened Michelson interferometer (FWMI) is developed to act as the
      spectral discriminator in high-spectral-resolution lidar (HSRL). This realization
      is motivated by the wide-angle Michelson interferometer (WAMI) which has been
      used broadly in the atmospheric wind and temperature detection. This paper
      describes an independent theoretical framework about the application of the FWMI
      in HSRL for the first time. In the framework, the operation principles and
      application requirements of the FWMI are discussed in comparison with that of the
      WAMI. Theoretical foundations for designing this type of interferometer are
      introduced based on these comparisons. Moreover, a general performance estimation
      model for the FWMI is established, which can provide common guidelines for the
      performance budget and evaluation of the FWMI in the both design and operation
      stages. Examples incorporating many practical imperfections or conditions that
      may degrade the performance of the FWMI are given to illustrate the
      implementation of the modeling. This theoretical framework presents a complete
      and powerful tool for solving most of theoretical or engineering problems
      encountered in the FWMI application, including the designing, parameter
      calibration, prior performance budget, posterior performance estimation, and so
      on. It will be a valuable contribution to the lidar community to develop a new
      generation of HSRLs based on the FWMI spectroscopic filter. 

PMID- 25969301
TI  - Densely packed waveguide array (DPWA) on a silicon chip for mode division
      multiplexing.
AB  - A densely packed waveguide array (DPWA) structure for mode division multiplexing
      on a silicon chip is proposed. The DPWA consists of several narrow waveguides
      with different widths, which are densely packed with gaps of 100nm. The lateral
      dimension of the DPWA is comparable to the conventional multimode waveguide used
      for mode division multiplexing on silicon. An efficient and parallel
      (de)multiplexing structure is proposed. For a three-mode DPWA with a 15MUm-long
      (de)multiplexing structure, insertion losses of -0.05dB and cross-talks of -20dB
      are achievable for all the modes in a wide wavelength range. The present DPWA
      favors a compact direct bending. In a 45MUm-radius 90 degrees  bend, insertion
      losses of -0.1dB and cross-talks of -20dB are obtained. The proposed DPWA
      structure also shows a large fabrication tolerance. 

PMID- 25969302
TI  - Millimeter-wave near-field imaging with bow-tie antennas.
AB  - A near-field reflectometry experiment operating at 60 GHz is built in view of
      material and circuit inspection. Experiments are always obtained in constant
      height mode of operation. The bow-tie near-field probe acts mostly as a linearly
      polarized electric dipole and allows strongly subwavelength resolution of ~
      lambda/130. Its interaction with sample is shown polarization dependent and
      sensitive to both the local topography and the local dielectric constant or metal
      conductivity. Resonant and non-resonant probes are both evaluated. 

PMID- 25969303
TI  - Low-loss silicon nitride waveguide hybridly integrated with colloidal quantum
      dots.
AB  - Silicon nitride waveguides with a monolayer of colloidal quantum dots embedded
      inside were fabricated using a low-temperature deposition process and an
      optimized dry etching step for the composite layers. We experimentally
      demonstrated the luminescence of the embedded quantum dots is preserved and the
      loss of these hybrid waveguide wires is as low as 2.69dB/cm at 900nm wavelength.
      This hybrid integration of low loss silicon nitride photonics with active
      emitters offers opportunities for optical sources operating over a very broad
      wavelength range. 

PMID- 25969304
TI  - Arbitrary waveform generator and differentiator employing an integrated optical
      pulse shaper.
AB  - We propose and demonstrate an optical arbitrary waveform generator and high-order
      photonic differentiator based on a four-tap finite impulse response (FIR) silicon
      on-insulator (SOI) on-chip circuit. Based on amplitude and phase modulation of
      each tap controlled by thermal heaters, we obtain several typical waveforms such
      as triangular waveform, sawtooth waveform, square waveform and Gaussian waveform,
      etc., assisted by an optical frequency comb injection. Unlike other proposed
      schemes, our scheme does not require a spectral disperser which is difficult to
      fabricate on chip with high resolution. In addition, we demonstrate first-,
      second- and third-order differentiators based on the optical pulse shaper. Our
      scheme can switch the differentiator patterns from first- to third-order freely.
      In addition, our scheme has distinct advantages of compactness, capability for
      integration with electronics. 

PMID- 25969305
TI  - Curvature-induced geometric momenta: the origin of waveguide dispersion of
      surface plasmons on metallic wires.
AB  - We show that the propagation of surface plasmon polaritons (SPPs) on metallic
      wires is governed by two solely curvature-induced geometric momenta, leading to a
      significant modification of the waveguide dispersion, i.e. a change of their
      phase velocity. By quantifying the azimuthal momentum and superimposing two
      planar SPPs of opposite helicity, we find an analytic expression for the
      dispersion of guided SPPs. This expression shows excellent agreement with
      numerical simulations and allows explaining fundamental SPP properties such as
      waveguide dispersion. 

PMID- 25969306
TI  - Feedback-based wavefront shaping.
AB  - Light scattering was thought to be the fundamental limitation for the depth at
      which optical imaging methods can retain their resolution and sensitivity.
      However, it was shown that light can be focused inside even the most strongly
      scattering objects by spatially shaping the wavefront of the incident light. This
      review summarizes recently developed feedback-based approaches for focusing light
      inside and through scattering objects. 

PMID- 25969307
TI  - Multi-spectral compressive snapshot imaging using RGB image sensors.
AB  - Compressive sensing is a powerful sensing and reconstruction framework for
      recovering high dimensional signals with only a handful of observations and for
      spectral imaging, compressive sensing offers a novel method of multispectral
      imaging. Specifically, the coded aperture snapshot spectral imager (CASSI) system
      has been demonstrated to produce multi-spectral data cubes color images from a
      single snapshot taken by a monochrome image sensor. In this paper, we expand the
      theoretical framework of CASSI to include the spectral sensitivity of the image
      sensor pixels to account for color and then investigate the impact on image
      quality using either a traditional color image sensor that spatially multiplexes
      red, green, and blue light filters or a novel Foveon image sensor which stacks
      red, green, and blue pixels on top of one another. 

PMID- 25969308
TI  - Advanced principal component analysis method for phase reconstruction.
AB  - Focus on the phase reconstruction from three phase-shifting interferograms with
      unknown phase shifts, an advanced principal component analysis method is
      proposed. First, use a simple subtraction operation among interferograms, two
      intensity difference images are obtained easily. Second, set the center region of
      the data of intensity difference images to zero, and then construct a covariance
      matrix to obtain a transformation matrix. Third, two principal components of
      interferograms can be determined by the Hotelling transform and then phase can be
      calculated from the two normalized principal components by an arctangent
      function. By means of the simulation calculation and the experimental research,
      it is proved that the phase with high precision can be obtained rapidly by the
      proposed algorithm. 

PMID- 25969309
TI  - Silicon photonic receiver and transmitter operating up to 36 Gb/s for lambda~1550
      nm.
AB  - We present the hybrid-integrated silicon photonic receiver and transmitter based
      on silicon photonic devices and 65 nm bulk CMOS interface circuits operating over
      30 Gb/s with a 10(-12) bit error rate (BER) for lambda ~1550nm. The silicon
      photonic receiver, operating up to 36 Gb/s, is based on a vertical-illumination
      type Ge-on-Si photodetector (Ge PD) hybrid-integrated with a CMOS receiver front
      end circuit (CMOS Rx IC), and exhibits high sensitivities of -11 dBm, -8 dBm, and
      -2 dBm for data rates of 25 Gb/s, 30 Gb/s and 36 Gb/s, respectively, at a BER of
      10(-12). The measured energy efficiency of the Si-photonic receiver is 2.6 pJ/bit
      at 25 Gb/s with an optical input power of -11 dBm, and 2.1 pJ/bit at 36 Gb/s with
      an optical power of -2 dBm. The hybrid-integrated silicon photonic transmitter,
      comprised of a depletion-type Mach-Zehnder modulator (MZM) and a CMOS driver
      circuit (CMOS Tx IC), shows better than 5.7 dB extinction ratio (ER) for 25 Gb/s,
      and 3 dB ER for 36 Gb/s. The silicon photonic transmitter achieves the data
      transmission with less than 10(-15) BER at 25 Gb/s, 10(-14) BER at 28 Gb/s, and 6
      x 10(-13) BER with the energy efficiency of ~6 pJ/bit at 30 Gb/s.

PMID- 25969310
TI  - Barrier-free absorbance modulation for super-resolution optical lithography.
AB  - Absorbance-Modulation-Optical Lithography (AMOL) enables super-resolution optical
      lithography by simultaneous illumination of a photochromic film by a bright spot
      at one wavelength, lambda1 and a node at another wavelength, lambda2. A deep
      subwavelength region of the transparent photochromic isomer is created in the
      vicinity of the node. Light at lambda1 penetrates this region and exposes an
      underlying photoresist layer. In conventional AMOL, a barrier layer is required
      to protect the photoresist from the photochromic layer. Here, we demonstrate
      barrier-free AMOL, which considerably simplifies the process. Specifically, we
      pattern lines as small as 70nm using lambda1 = 325nm and lambda2 = 647nm. We
      further elucidate the minimum requirements for AMOL to enable multiple exposures
      so as to break the diffraction limit.

PMID- 25969311
TI  - Orbital angular momentum mode-demultiplexing scheme with partial angular
      receiving aperture.
AB  - For long distance orbital angular momentum (OAM) based transmission, the
      conventional whole beam receiving scheme encounters the difficulty of large
      aperture due to the divergence of OAM beams. We propose a novel partial receiving
      scheme, using a restricted angular aperture to receive and demultiplex multi-OAM
      mode beams. The scheme is theoretically analyzed to show that a regularly spaced
      OAM mode set remain orthogonal and therefore can be de-multiplexed. Experiments
      have been carried out to verify the feasibility. This partial receiving scheme
      can serve as an effective method with both space and cost savings for the OAM
      communications. It is applicable to both free space OAM optical communications
      and radio frequency (RF) OAM communications. 

PMID- 25969312
TI  - First-order analysis of zoom system based on variable focal power lens.
AB  - We present our analysis of a zoom system based on the variable focal power lens,
      and we demonstrate how our analysis can be used in zoom system design. The
      transverse magnification is considered as an independent first-order optics
      control parameter in the zoom system. The zoom system equations are established
      through the use of matrix optics. Formulas related to the zoom principles and
      performance of such optical systems are derived, and numerical and theoretical
      values are compared using examples. 

PMID- 25969313
TI  - Ultrabroadband radio-frequency arbitrary waveform generation with high-speed
      phase and amplitude modulation capability.
AB  - We introduce a novel photonic-assisted ultrabroadband radio-frequency arbitrary
      waveform generation setup capable of high-speed phase and amplitude modulation of
      the individual arbitrary waveforms. The waveform generator is based on an optical
      interferometer, within which a high-resolution optical pulse shaper and
      integrated optic phase and intensity modulators are placed, followed by frequency
      to-time mapping. The phase and amplitude of each ultrabroadband waveform within
      the generated sequence can be continuously tuned by adjusting the driving
      voltages applied to the phase and intensity modulator pair, hence overcoming the
      slow update speed of conventional spatial light modulator-based pulse shapers.
      Moreover, this data modulation is completely independent from and does not
      interfere with RF waveform design. Programmable ultrabroadband RF sequences,
      spanning more than 4.7 octaves from 2 to 52 GHz, are modulated with real-time
      data in up to 16 level, M-ary phase-shift keying and quadrature amplitude
      modulation formats. 

PMID- 25969314
TI  - Large-angle and high-efficiency tunable phase grating using fringe field
      switching liquid crystal.
AB  - We propose a switchable phase grating using fringe field switching (FFS) cells.
      The FFS phase grating possesses several attractive features: large diffraction
      angle, high diffraction efficiency, fast response time, and high contrast ratio.
      It can diffract >32% light to +/- 2nd orders with a large diffraction angle of
      12.1 degrees . Meanwhile, its response time remains relatively fast even at -40
      degrees C. A simulation model is developed to explain the experimental results
      and good agreement is obtained. We also demonstrate a blazed phase grating to
      achieve tunable beam steering between 0th, 1st and 2nd orders. 

PMID- 25969315
TI  - Analysis of mid-infrared lasing in active random media.
AB  - Lasing behaviour of 2-dimensional active random structures, designed to work in
      the Mid-IR region, has been investigated at different input powers by varying the
      amount of scattering intensity. A Monte Carlo based simulation tool has been
      developed including a model to manage the optical amplification. The analysis of
      photon travel distance has been considered to show the random lasing behaviour
      with particular attention on lasing threshold at different scattering intensity.
      The simulated results are in agreement with experiments. 

PMID- 25969316
TI  - Statistics and control of waves in disordered media.
AB  - Fundamental concepts in the quasi-one-dimensional geometry of disordered wires
      and random waveguides in which ideas of scaling and the transmission matrix were
      first introduced are reviewed. We discuss the use of the transmission matrix to
      describe the scaling, fluctuations, delay time, density of states, and control of
      waves propagating through and within disordered systems. Microwave measurements,
      random matrix theory calculations, and computer simulations are employed to study
      the statistics of transmission and focusing in single samples and the scaling of
      the probability distribution of transmission and transmittance in random
      ensembles. Finally, we explore the disposition of the energy density of
      transmission eigenchannels inside random media. 

PMID- 25969317
TI  - Long-term operation of surface high-harmonic generation from relativistic
      oscillating mirrors using a spooling tape.
AB  - Surface high-harmonic generation in the relativistic regime is demonstrated as a
      source of extreme ultra-violet (XUV) pulses with extended operation time.
      Relativistic high-harmonic generation is driven by a frequency-doubled high-power
      Ti:Sapphire laser focused to a peak intensity of 3.10(19) W/cm2 onto spooling
      tapes. We demonstrate continuous operation over up to one hour runtime at a
      repetition rate of 1 Hz. Harmonic spectra ranging from 20 eV to 70 eV (62 nm to
      18 nm) were consecutively recorded by an XUV spectrometer. An average XUV pulse
      energy in the uJ range is measured. With the presented setup, relativistic
      surface high-harmonic generation becomes a powerful source of coherent XUV pulses
      that might enable applications in, e.g. attosecond laser physics and the seeding
      of free-electron lasers, when the laser issues causing 80-% pulse energy
      fluctuations are overcome.

PMID- 25969318
TI  - Investigation of a versatile pulsed laser source based on a diode seed and ultra
      high gain bounce geometry amplifiers.
AB  - We present an investigation of a versatile pulsed laser source using a low power,
      gain-switched diode laser with independently variable repetition rate and pulse
      duration to seed an ultra-high gain Nd:YVO4 bounce geometry amplifier system at
      1064nm. Small-signal gain as high as 50dB was demonstrated in a bounce geometry
      pre-amplifier from just 24W pumping, with good preservation of TEM00 beam
      quality. The single amplifier is shown to be limited by amplified spontaneous
      emission. Study is made of further scaling with a second power amplifier,
      achieving average output power of ~14W for a pulsed diode seed input of 188MUW.
      This investigation provides some guidelines for using the bounce amplifier to
      obtain flexible pulse amplification of low-power seed sources to reach
      scientifically and commercially useful power levels.

PMID- 25969319
TI  - Focusing and imaging in microsphere-based microscopy.
AB  - Microsphere-based microscopy systems have garnered lots of recent interest,
      mainly due to their capacity in focusing light and imaging beyond the diffraction
      limit. In this paper, we present theoretical foundations for studying the optical
      performance of such systems by developing a complete theoretical model
      encompassing the aspects of illumination, sample interaction and
      imaging/collection. Using this model, we show that surface waves play a
      significant role in focusing and imaging with the microsphere. We also show that
      by designing a radially polarized convergent beam, we can focus to a spot smaller
      than the diffraction limit. By exploiting surface waves, we are able to resolve
      two dipoles spaced 98 nm apart in simulation using light at a wavelength of
      402.292 nm. Using our model, we also explore the effect of beam geometry and
      polarization on optical resolution and focal spot size, showing that both
      geometry and polarization greatly affect the shape of the spot. 

PMID- 25969320
TI  - Demonstration of record-low injection-current variable optical attenuator based
      on strained SiGe with optimized lateral pin junction.
AB  - We demonstrate a strained SiGe variable optical attenuator (VOA) with a lateral
      pin junction which exhibits record-low injection-current for 20-dB attenuation.
      We optimize the distance between the highly doped p + and n + regions in the
      lateral pin junction to effectively inject electrons and holes, taking into
      account the propagation loss. In conjunction with the enhanced free-carrier
      absorption in strained SiGe, the SiGe VOA with the optimized lateral pin junction
      exhibits 20-dB attenuation by 20-mA/mm injection current, which is 1.5 times
      lower current density than that of the Si VOA. The SiGe VOA also shows better RF
      response than the Si VOA due to the short carrier lifetime in SiGe, allowing us
      to achieve efficient and fast attenuation modulation simultaneously. Furthermore,
      2-GHz switching and error-free transmission of 4 * 12.5 Gbps WDM signal have been
      also achieved. 

PMID- 25969321
TI  - High direct drive illumination uniformity achieved by multi-parameter
      optimization approach: a case study of Shenguang III laser facility.
AB  - The uniformity of the compression driver is of fundamental importance for
      inertial confinement fusion (ICF). In this paper, the illumination uniformity on
      a spherical capsule during the initial imprinting phase directly driven by laser
      beams has been considered. We aim to explore methods to achieve high direct drive
      illumination uniformity on laser facilities designed for indirect drive ICF.
      There are many parameters that would affect the irradiation uniformity, such as
      Polar Direct Drive displacement quantity, capsule radius, laser spot size and
      intensity distribution within a laser beam. A novel approach to reduce the root
      mean square illumination non-uniformity based on multi-parameter optimizing
      approach (particle swarm optimization) is proposed, which enables us to obtain a
      set of optimal parameters over a large parameter space. Finally, this method is
      applied to improve the direct drive illumination uniformity provided by Shenguang
      III laser facility and the illumination non-uniformity is reduced from 5.62% to
      0.23% for perfectly balanced beams. Moreover, beam errors (power imbalance and
      pointing error) are taken into account to provide a more practical solution and
      results show that this multi-parameter optimization approach is effective. 

PMID- 25969322
TI  - Generation of intense subcycle optical pulses in a gas.
AB  - The generation of intense subcycle laser pulses during the propagation of two
      color femtosecond pulses in a gas medium is investigated theoretically and
      experimentally. Four-wave mixing induced by the laser pulses in a gas medium
      generates multi-octave laser radiation from the ultraviolet to the infrared,
      which forms stable subcycle laser pulses after a certain propagation distance in
      a gas medium with group-velocity dispersion. The intense subcycle laser pulses
      would allow the coherent control of the waveforms of soft-x-rays generated via
      high-harmonic generation. 

PMID- 25969323
TI  - Layered ACO-OFDM for intensity-modulated direct-detection optical wireless
      transmission.
AB  - Layered asymmetrically clipped optical orthogonal frequency division multiplexing
      (ACO-OFDM) with high spectral efficiency is proposed in this paper for optical
      wireless transmission employing intensity modulation with direct detection. In
      contrast to the conventional ACO-OFDM, which only utilizes odd subcarriers for
      modulation, leading to an obvious spectral efficiency loss, in layered ACO-OFDM,
      the subcarriers are divided into different layers and modulated by different
      kinds of ACO-OFDM, which are combined for simultaneous transmission. In this way,
      more subcarriers are used for data transmission and the spectral efficiency is
      improved. An iterative receiver is also proposed for layered ACO-OFDM, where the
      negative clipping distortion of each layer is subtracted once it is detected so
      that the signals from different layers can be recovered. Theoretical analysis
      shows that the proposed scheme can improve the spectral efficiency by up to 2
      times compared with conventional ACO-OFDM approaches with the same modulation
      order. Meanwhile, simulation results confirm a considerable signal-to-noise ratio
      gain over ACO-OFDM at the same spectral efficiency. 

PMID- 25969324
TI  - Mode stabilization of a laterally structured broad area diode laser using an
      external volume Bragg grating.
AB  - An external volume Bragg grating (VBG) is used for transverse and longitudinal
      mode stabilization of a broad area diode laser (BAL) with an on-chip transverse
      Bragg resonance (TBR) grating. The internal TBR grating defines a transverse low
      loss mode at a specific propagation angle inside the BAL. Selection of the TBR
      mode was realized via the angular geometry of an external resonator assembly
      consisting of the TBR BAL and a feedback element. A feedback mirror provides near
      diffraction limited and spectral narrow output in the TBR mode albeit requiring
      an intricate alignment procedure. If feedback is provided via a VBG, adjustment
      proves to be far less critical and higher output powers were achieved. Moreover,
      additional modulation in the far field distribution became discernible allowing
      for a better study of the TBR concept. 

PMID- 25969325
TI  - Enhanced performances of diode-pumped sapphire/Er3+:Yb3+:LuAl3(BO3)4/sapphire
      micro-laser at 1.5-1.6 MUm.
AB  - A sandwich-type sapphire/Er3+:Yb3+:LuAl3(BO3)4/sapphire micro-laser was
      fabricated by tightly pressing two sapphire crystals and a Er3+:Yb3+:LuAl3(BO3)4
      microchip together, and directly depositing cavity mirrors onto the outside
      surfaces of the sapphire crystals. Pumped by a continuous-wave 976 nm diode
      laser, a 1543 nm laser with maximum output power of 1.17 W and slope efficiency
      of 33% with respect to incident pump power was realized in the sandwich-type
      micro-laser, whereas a laser with maximum output power of 0.46 W and slope
      efficiency of 17% was obtained in a monolithic Er3+:Yb3+:LuAl3(BO3)4 micro-laser.
      Furthermore, efficient 1521 nm continuous-wave and passively Q-switched pulse
      lasers were also demonstrated in the sandwich-type micro-laser.

PMID- 25969326
TI  - Cascaded multi-dithering theory for coherent beam combining of multiplexed beam
      elements.
AB  - The Cascaded Multi-Dithering theory, which allows coherent beam combining of M-by
      N beam elements, is presented in this paper. The theory of Cascaded Multi
      Dithering is briefly introduced, and demonstrated experimentally by combining
      sixteen-beams to verify its feasibility as an active phase control for scaling up
      the power of fiber lasers. 

PMID- 25969327
TI  - Experimental investigation on a diode-pumped cesium-vapor laser stably operated
      at continuous-wave and pulse regime.
AB  - Employing a fiber-coupled diode-laser with a center wavelength of 852.25 nm and a
      line width of 0.17 nm, experimental investigation on diode-end-pumped cesium (Cs)
      vapor laser stably operated at continuous-wave (CW) and pulse regime is carried
      out. A 5 mm long cesium vapor cell filled with 60 kPa helium and 20 kPa ethane is
      used as laser medium. Using an output coupler with reflectivity of 48.79%, 1.26 W
      894.57 nm CW laser is obtained at an incident pump power of 4.76 W, corresponding
      an optical-optical efficiency of 26.8% and a slope-efficiency of 28.8%,
      respectively. The threshold temperature is 67.5  degrees C. Stable pulsed cesium
      laser with a maximum average output power of 2.6 W is obtained at a repetition
      rate of 76 Hz, and the pulse repetition rate can be extend to 1 kHz with a pulse
      width of 18 MUs. 

PMID- 25969328
TI  - Homogeneity of bismuth-distribution in bismuth-doped alkali germanate laser
      glasses towards superbroad fiber amplifiers.
AB  - Compared to rare-earth doped glasses, bismuth-doped glasses hold promise for
      super-broadband near-infrared (NIR) photoemission and potential applications in
      optical amplification. However, optically active bismuth centers are extremely
      sensitive to the properties of the surrounding matrix, and also to processing
      conditions. This is strongly complicating the exploitation of this class of
      materials, because functional devices require a very delicate adjustment of the
      redox state of the bismuth species, and its distribution throughout the bulk of
      the material. It also largely limits some of the conventional processing routes
      for glass fiber, which start from gas phase deposition and may require very high
      processing temperature. Here, we investigate the influence of melting time and
      alkali addition on bismuth-related NIR photoluminescence from melt-derived
      germanate glasses. We show that the effect of melting time on bismuth-related
      absorption and NIR photoemission is primarily through bismuth volatilization.
      Adding alkali oxides as fluxing agents, the melt viscosity can be lowered to
      reduce either the glass melting temperature, or the melting time, or both. At the
      same time, however, alkali addition also leads to increasing mean-field basicity,
      what may reduce the intensity of bismuth-related NIR emission. Preferentially
      using Li2O over Na2O or K2O presents the best trade-off between those above
      factors, because its local effect may be adverse to the generally assumed trend
      of the negative influence of more basic matrix composition. This observation
      provides an important guideline for the design of melt-derived Bi-doped glasses
      with efficient NIR photoemission and high optical homogeneity.

PMID- 25969329
TI  - Diffraction management and soliton dynamics in frequency-chirped PT symmetric
      lattices.
AB  - We address two closely related problems: diffraction management and soliton
      dynamics in parity-time ( PT) symmetric lattices with a quadratic frequency
      modulation. The normal, anomalous, or zero diffraction is possible for narrow
      beams with a broad band of spatial frequencies. The frequency band of
      nondiffraction beams can be enlarged by increasing the chirp rate of lattices.
      Counter-intuitively, the gain-loss component plays the same role as the real part
      of lattice on the suppression of diffraction, which leads to an effective
      reduction of critical lattice depth for nondiffraction beams. Additionally, we
      reveal the existence of a novel type of "bright" solitons in defocusing Kerr
      media modulated by chirped PT lattices. We also demonstrate that lattice chirp
      can be utilized to suppress the instability of solitons. Our results expand the
      concept of PT symmetry in both linear and nonlinear regimes, and may find
      interesting optical applications. 

PMID- 25969330
TI  - Visualizing polarization singularities in Bessel-Poincare beams.
AB  - We demonstrate that an annulus of light whose polarization is linear at each
      point, but the plane of polarization gradually rotates by pi radians can be used
      to generate Bessel-Poincare beams. In any transverse plane this beam exhibits
      concentric rings of polarization singularities in the form of L-lines, where the
      polarization is purely linear. Although the L-lines are invisible in terms of
      light intensity variations, we present a simple way to visualize them as dark
      rings around a sharp peak of intensity in the beam center. To do this we use a
      segmented polarizer whose transmission axes are oriented differently in each
      segment. The radius of the first L-line is always smaller than the radius of the
      central disk of the zero-order Bessel beam that would be produced if the annulus
      were homogeneously polarized and had no phase circulation along it. 

PMID- 25969331
TI  - Twist phase-induced changes of the statistical properties of a stochastic
      electromagnetic beam propagating in a uniaxial crystal.
AB  - With the help of a tensor method, an analytical formula is derived for the cross
      spectral density matrix of a twisted electromagnetic Gaussian Schell-model (EGSM)
      beam (i.e., EGSM beam with twist phase) propagating in a uniaxial crystal
      orthogonal to the optical axis. The twist phase-induced changes of the
      statistical properties, such as the spectral density, the degree of polarization
      and the degree of coherence, of an EGSM beam propagating in a uniaxial crystal
      are illustrated numerically. It is found that the distributions of the spectral
      density, the degree of polarization and the degree of coherence of a twisted EGSM
      beam in a uniaxial crystal all exhibit non-circular symmetries, which are quite
      different from those of a twisted EGSM beam in isotropic medium or in free space.
      One may use uniaxial crystal to determine whether an EGSM beam carries twist
      phase or not. 

PMID- 25969332
TI  - Picosecond optically reconfigurable filters exploiting full free spectral range
      tuning of single ring and Vernier effect resonators.
AB  - We demonstrate that phase shifts larger than 2pi can be induced by all-optical
      tuning in silicon waveguides of a few micrometers in length. By generating high
      concentrations of free carriers in the silicon employing absorption of
      ultrashort, ultraviolet laser pulses, the refractive index of silicon can be
      drastically reduced. As a result, the resonance wavelength of optical resonators
      can be freely tuned over the full free spectral range. This allows for active
      integrated optic devices that can be switched with GHz frequencies into any
      desired state by all-optical means. 

PMID- 25969333
TI  - Abundance- and functional-based mechanisms of plant diversity loss with
      fertilization in the presence and absence of herbivores.
AB  - Nutrient supply and herbivores can regulate plant species composition,
      biodiversity and functioning of terrestrial ecosystems. Nutrient enrichment
      frequently increases plant productivity and decreases diversity while herbivores
      tend to maintain plant diversity in productive systems. However, the mechanisms
      by which nutrient enrichment and herbivores regulate plant diversity remain
      unclear. Abundance-based mechanisms propose that fertilization leads to the
      extinction of rare species due to random loss of individuals of all species. In
      contrast, functional-based mechanisms propose that species exclusion is based on
      functional traits which are disadvantageous under fertilized conditions. We
      tested mechanistic links between fertilization and diversity loss in the presence
      or absence of consumers using data from a 4-year fertilization and fencing
      experiment in an alpine meadow. We found that both abundance- and functional
      based mechanisms simultaneously affected species loss in the absence of
      herbivores while only abundance-based mechanisms affected species loss in the
      presence of herbivores. Our results indicate that an abundance-based mechanism
      may consistently play a role in the loss of plant diversity with fertilization,
      and that diversity decline is driven primarily by the loss of rare species
      regardless of a plant's functional traits and whether or not herbivores are
      present. Increasing efforts to conserve rare species in the context of ecosystem
      eutrophication is a central challenge for grazed grassland ecosystems. 

PMID- 25969334
TI  - Traits influencing range contraction in New Zealand's endemic forest birds.
AB  - Understanding vulnerability of endemic taxa to predation is clearly important for
      conservation management. In New Zealand, predation by introduced mammals such as
      rats and mustelids is widely recognized as the primary factor responsible for
      declines of indigenous fauna. The aim of our study was to evaluate the
      vulnerability of New Zealand's surviving endemic forest bird species to impacts
      of introduced mammalian predators, and identify key life history attributes
      underlying this vulnerability. We measured range contraction following the
      introduction of exotic mammalian predators for 23 endemic forest bird species
      using information on both pre-human and current distributions. We used Bayesian
      modeling techniques to analyze whether variation in range contraction was
      associated with life history traits potentially influencing species' predation
      vulnerability, while accounting for phylogenetic relatedness. Our results showed
      that the extent of range contraction varied greatly among species, with some
      species remaining in available forest habitat throughout most of their pre-human
      range, and others having disappeared completely from the main islands. Cavity
      nesting was the key trait associated with more extensive range decline,
      suggesting that cavity-nesting species are more vulnerable to predation than
      species that nest in more open sites. 

PMID- 25969335
TI  - Enhanced equivalence class formation by the delay and relational functions of
      meaningful stimuli.
AB  - Undergraduates in six groups of 10 attempted to form three 3-node 5-member
      equivalence classes (A -> B -> C -> D -> E) under the simultaneous protocol. In
      five of six groups, all stimuli were abstract shapes; in the PIC group, C stimuli
      were pictures with the remainder being abstract shapes. Before class formation,
      participants in the Identity-S and Identity-D groups were given preliminary
      training to form identity conditional discriminations with the C stimuli using
      simultaneous and 6 s delayed matching-to-sample procedures, respectively. In the
      Arbitrary-S and Arbitrary-D groups, before class formation, arbitrary conditional
      discriminations were formed between C and X stimuli using simultaneous and 6 s
      delayed matching-to-sample procedures, respectively. With no preliminary
      training, classes in the PIC and ABS groups were formed by 80% and 0% of
      participants, respectively. After preliminary training, class formation (yield)
      increased with delay, regardless of relational type. For each of the two delays,
      yield was slightly greater after forming arbitrary- instead of identity
      relations. Yield was greatest, however, when a class contained a meaningful
      stimulus (PIC). During failed class formation, probes produced experimenter
      defined relations, participant-defined relations, and unsystematic responding;
      delay, but not the relation type in preliminary training influenced relational
      and indeterminate responding. These results suggest how meaningful stimuli
      enhance equivalence class formation.

PMID- 25969336
TI  - Contextual control using a go/no-go procedure with compound abstract stimuli.
AB  - Contextual control has been described as (1) a five-term contingency, in which
      the contextual stimulus exerts conditional control over conditional
      discriminations, and (2) allowing one stimulus to be a member of different
      equivalence classes without merging them into one. Matching-to-sample is the most
      commonly employed procedure to produce and study contextual control. The present
      study evaluated whether the go/no-go procedure with compound stimuli produces
      equivalence classes that share stimuli. This procedure does not allow the
      identification of specific stimulus functions (e.g., contextual, conditional, or
      discriminative functions). If equivalence classes were established with this
      procedure, then only the latter part of the contextual control definition (2)
      would be met. Six undergraduate students participated in the present study. In
      the training phases, responses to AC, BD, and XY compounds with stimuli from the
      same classes were reinforced, and responses to AC, BD, and XY compounds with
      stimuli from different classes were not. In addition, responses to X1A1B1,
      X1A2B2, X2A1B2, and X2A2B1 compounds were reinforced and responses to the other
      combinations were not. During the tests, the participants had to respond to new
      combinations of stimuli compounds YCD to indicate the formation of four
      equivalence classes that share stimuli: X1A1B1Y1C1D1, X1A2B2Y1C2D2, X2A1B2Y2C1D2,
      and X2A2B1Y2C2D1. Four of the six participants showed the establishment of these
      classes. These results indicate that establishing contextual stimulus functions
      is unnecessary to produce equivalence classes that share stimuli. Therefore,
      these results are inconsistent with the first part of the definition of
      contextual control. 

PMID- 25969337
TI  - Multivariate Exploratory Analysis of Metals and Phosphorus Concentrations of
      Leachates Collected Monthly from a Municipal Sanitary Landfill.
AB  - Concentrations of 11 elements (P, Cu, Ni, Co, Pb, Ca, Mn, Fe, Zn, Cr and Al) were
      measured in leachate samples collected monthly from the municipal landfill in
      Jequie, Bahia, Brazil. P (0.943-23.8 mg L(-1)), Ca (19.90-129 mg L(-1)) and Fe
      (0.115-2.87 mg L(-1)) were found in the highest levels, while Cu (<LOQ-0.230 mg
      L(-1)), Ni (<LOQ-0.540 mg L(-1)), Co (<LOQ-0.268 mg L(-1)), Pb (<LOQ-0.563 mg L(
      1)), Mn (<LOQ-3.40 mg L(-1)), Zn (<LOQ-0.594 mg L(-1)), Cr (<LOQ-0.163 mg L(-1))
      and Al (<LOQ-2.27 mg L(-1)) were found in lower concentrations. Principal
      components analysis and hierarchical clustering analysis revealed two distinct
      groups associated with dry and rainy periods. Overall, this study revealed that
      concentrations of elements in landfill leachate vary temporally, and rainfall
      strongly influences their levels.

PMID- 25969338
TI  - Inhibition of soluble epoxide hydrolase counteracts the development of renal
      dysfunction and progression of congestive heart failure in Ren-2 transgenic
      hypertensive rats with aorto-caval fistula.
AB  - The detailed mechanisms determining the course of congestive heart failure (CHF)
      in hypertensive subjects with associated renal dysfunction remain unclear. In Ren
      2 transgenic rats (TGR), a model of angiotensin II (ANG II)-dependent
      hypertension, CHF was induced by volume overload achieved by creation of the
      aorto-caval fistula (ACF). In these rats we investigated the putative
      pathophysiological contribution of epoxyeicosatrienoic acids (EETs) and compared
      it with the role of the renin-angiotensin system (RAS). We found that untreated
      ACF TGR exhibited marked intrarenal and myocardial deficiency of EETs and
      impairment of renal function. Chronic treatment of these rats with cis-4-[4-(3
      adamantan-1-yl-ureido)cyclohexyloxy]benzoic acid (c-AUCB, 3 mg/L in drinking
      water), an inhibitor of soluble epoxide hydrolase (sEH) which normally degrades
      EETs, increased intrarenal and myocardial EETs, markedly improved survival rate,
      and increased renal blood flow, glomerular filtration rate and fractional sodium
      excretion, without altering RAS activity. Chronic angiotensin-converting enzyme
      inhibition (ACEi) with trandolapril, (6 mg/L in drinking water) improved survival
      rate even more, and also inhibited the development of renal dysfunction; these
      beneficial actions were associated with significant suppression of the
      vasoconstrictor/sodium retaining axis and further activation of the
      vasodilatory/natriuretic axis of the systemic and intrarenal RAS, without
      modifying tissue availability of biologically active fatty acid epoxides. In
      conclusion, these findings strongly suggest that chronic sEH inhibition and
      chronic treatment with ACEi, each of them altering a different vasoactive system,
      delay or even prevent the onset of decompensation of CHF in ACF TGR, probably by
      preventing the development of renal dysfunction.

PMID- 25969339
TI  - Illness perception and fibromyalgia impact on female patients from Spain and the
      Netherlands: do cultural differences exist?
AB  - The purpose of this study was to examine the differences in illness perception
      and overall impact on fibromyalgia females from Spain and the Netherlands. A
      total of 325 fibromyalgia females from Spain (54.3 +/- 7.1 years) and the
      Netherlands (51.8 +/- 7.2 years) participated in the study. Illness perception
      and impact of fibromyalgia were assessed by the Revised Illness Perception
      Questionnaire and the Fibromyalgia Impact Questionnaire, respectively. Spanish
      fibromyalgia females perceived more symptoms related to their fibromyalgia
      (identity) such as nausea, breathlessness, wheezing or fatigue (P < 0.001) and
      had greater emotional representation (P < 0.01). Dutch fibromyalgia females
      experienced less timeline (acute/chronic) and consequences (all, P < 0.05), had a
      better cyclical timeline, personal control, treatment control and illness
      coherence (all, P < 0.001). Spanish fibromyalgia females reported higher impact
      of fibromyalgia than Dutch females (61.2 + 14.8 vs. 54.9 + 16.4, respectively; P
      < 0.001), but the effect size was small (Cohen's d = 0.41) . Impact of
      fibromyalgia and negative views of fibromyalgia were higher in Spanish
      fibromyalgia females, whereas Dutch fibromyalgia females presented higher score
      of positive beliefs about the controllability of the illness. Psychological
      interventions which help patients to cope with their illness perception might
      lead to an improvement of the impact of the disease on fibromyalgia females. 

PMID- 25969340
TI  - Dissociative subtype of DSM-5 posttraumatic stress disorder in U.S. veterans.
AB  - The Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5)
      formally introduced a dissociative subtype of posttraumatic stress disorder
      (PTSD). This study examined the proportion of U.S. veterans with DSM-5 PTSD that
      report dissociative symptoms; and compared veterans with PTSD with and without
      the dissociative subtype and trauma-exposed controls on sociodemographics,
      clinical characteristics, and quality of life. Multivariable analyses were
      conducted on a nationally representative sample of 1484 veterans from the
      National Health and Resilience in Veterans Study (second baseline survey
      conducted September-October, 2013). Of the 12.0% and 5.2% of veterans who
      screened positive for lifetime and past-month DSM-5 PTSD, 19.2% and 16.1%
      screened positive for the dissociative subtype, respectively. Among veterans with
      PTSD, those with the dissociative subtype reported more severe PTSD symptoms,
      comorbid depressive and anxiety symptoms, alcohol use problems, and hostility
      than those without the dissociative subtype. Adjusting for PTSD symptom severity,
      those with the dissociative subtype continued to report more depression and
      alcohol use problems. These results underscore the importance of assessing,
      monitoring, and treating the considerable proportion of veterans with PTSD and
      dissociative symptoms. 

PMID- 25969341
TI  - The level of evidence for emergency department performance indicators: systematic
      review.
AB  - The aim of this study was to perform a comprehensive systematic review of
      emergency department performance indicators in relation to evidence. A systematic
      search was performed through PUBMED, EMBASE, CINAHL and COCHRANE databases with
      (and including synonyms of) the search words: [emergency medicine OR emergency
      department] AND [quality indicator(s) OR performance indicator(s) OR performance
      measure(s)]. Articles were included according to the inclusion/exclusion criteria
      using the PRISMA protocol. The level of evidence was rated according to the
      evidence levels by the Oxford Centre for Evidence-Based Medicine. Performance
      indicators were extracted and organized into five categories; outcome, process,
      satisfaction, equity and structural/organizational measures. Six thousand four
      hundred and forty articles were initially identified; 127 provided evidence
      for/against a minimum of one performance indicator: these were included for
      further study. Of the 127 articles included, 113 (92%) were primary research
      studies and only nine (8%) were systematic reviews. Within the 127 articles, we
      found evidence for 202 individual indicators. Approximately half (n=104) of all
      this evidence (n=202) studied process-type indicators. Only seven articles (6%)
      qualified for high quality (level 1b). Sixty-six articles (51%) were good
      retrospective quality (level 2b or better), whereas the remaining articles were
      either intermediate quality (25% level 3a or 3b) or poor quality (17% level 4 or
      5). We found limited evidence for most emergency department performance
      indicators, with the majority presenting a low level of evidence. Thus, a core
      group of evidence-based performance indicators cannot currently be recommended on
      the basis of this broad review of the literature. 

PMID- 25969342
TI  - A case management intervention targeted to reduce healthcare consumption for
      frequent Emergency Department visitors: results from an adaptive randomized
      trial.
AB  - BACKGROUND: A small group of frequent visitors to Emergency Departments accounts
      for a disproportionally large fraction of healthcare consumption including
      unplanned hospitalizations and overall healthcare costs. In response, several
      case and disease management programs aimed at reducing healthcare consumption in
      this group have been tested; however, results vary widely. OBJECTIVES: To
      investigate whether a telephone-based, nurse-led case management intervention can
      reduce healthcare consumption for frequent Emergency Department visitors in a
      large-scale setup. METHODS: A total of 12 181 frequent Emergency Department users
      in three counties in Sweden were randomized using Zelen's design or a traditional
      randomized design to receive either a nurse-led case management intervention or
      no intervention, and were followed for healthcare consumption for up to 2 years.
      RESULTS: The traditional design showed an overall 12% (95% confidence interval 4
      19%) decreased rate of hospitalization, which was mostly driven by effects in the
      last year. Similar results were achieved in the Zelen studies, with a significant
      reduction in hospitalization in the last year, but mixed results in the early
      development of the project. CONCLUSION: Our study provides evidence that a
      carefully designed telephone-based intervention with accurate and systematic
      patient selection and appropriate staff training in a centralized setup can lead
      to significant decreases in healthcare consumption and costs. Further, our
      results also show that the effects are sensitive to the delivery model chosen.

PMID- 25969343
TI  - Management of body stuffers presenting to the emergency department.
AB  - OBJECTIVE: The aim of this study was to establish a management protocol for body
      stuffers presenting to the emergency department. METHODS: This is a retrospective
      observational case series of patients presenting to the emergency department of a
      large inner-city hospital as 'body stuffers' during the period between 1 January
      2006 and 31 October 2011, irrespective of the type of drug ingested. We reviewed
      demographic data, ingestion characteristics, clinical progress and outcome.
      RESULTS: A total of 126 patients were included in the study, with a mean age of
      31+/-8.10 years (range 15-58 years), among whom 106 were male (84%). Drugs
      ingested were as follows: heroin (n=61, 48%), cocaine (n=58, 46%), other drugs
      (n=20, 16%) and unknown (n=10, 8%). Of the patients, 23 (18%) ingested more than
      one drug. At presentation, 96 had features of drug toxicity. The presence of
      depressant drug toxidrome was more commonly observed among heroin users, but
      stimulant drug toxidromes were seen across all groups. Of the patients, 12
      developed changes in clinical state, with a mean time to development of symptoms
      of 2 h 50 min+/-1 h 39 min (range from 1 h 0 min to 5 h 36 min). Abdominal
      radiography showed the presence of foreign bodies in 8% of the tests performed,
      and packets were recovered from one patient who underwent gut decontamination.
      CONCLUSION: Patients developed new or worsening features of drug toxicity within
      6 h of presentation. Toxidromes observed are often not drug/class specific, and
      treatment including gut decontamination and radiography do not aid in expediting
      discharge. We propose an observation period of 6 h from the time of admission as
      the time required if the patient is asymptomatic or there is resolution of
      presenting signs and symptoms.

PMID- 25969344
TI  - Diagnosis of ruptured abdominal aortic aneurysm: a multicentre cohort study.
AB  - OBJECTIVE: The aim of this study was to describe the presentation of patients
      with ruptured abdominal aortic aneurysm (rAAA) and identify factors contributing
      toward misdiagnosis. METHODS: This was an observational study of cases with a
      final diagnosis of rAAA assessed at nine Emergency Departments and managed at one
      of two regional vascular centres in the UK. RESULTS: Eighty-five consecutive
      cases were included. Seventeen [20.0%, 95% confidence interval (CI) 11.5-28.5%]
      patients reported important symptoms up to 3 weeks before index presentation. In
      the Emergency Department, most patients complained of abdominal and/or back pain,
      seven (8.2%, 95% CI 2.4-14.0%) additionally reported atypical pain and ten
      (11.8%, 95% CI 4.9-18.7%) denied pain altogether. Hypotension (36.5%, 95% CI 26.3
      46.7%), tachycardia (18.8%, 95% CI 10.5-27.1%) and syncope (36.5%, 95% CI 26.3
      46.7%) were documented in a minority of cases. Distracting symptoms were present
      in 33 (38.8%, 95% CI 28.4-49.2%) patients. The median time to diagnosis was 17.5
      min (range immediate-12 days), and 21 (25.6%, 95% CI 16.3-34.9%) patients were
      misdiagnosed during clinical assessment. CONCLUSION: The classical signs and
      symptoms or rAAA are not always present and patients frequently show additional
      features that may confound the diagnosis. A high level of suspicion should be
      adopted for rAAA alongside a low threshold for immediate computed tomography.
      Further research is required to develop an objective clinical risk score or
      predictive tool for characterizing patients at risk.

PMID- 25969345
TI  - Outcomes of electrical injuries in the emergency department: a 10-year
      retrospective study.
AB  - OBJECTIVE: Electrical injuries are challenging to assess and current guidelines
      are based on few studies and case reports. Recommendations on cardiac monitoring
      were published for certain risk factors, but indications for hospital observation
      are less clear. Furthermore, the risk of late arrhythmias is not known.
      Therefore, we aimed to assess possible cardiac complications, including death and
      immediate or delayed dysrhythmia, after an electrical accident in a sample of
      patients presenting to the Emergency Department (ED). METHODS: Medical records of
      patients presenting to the ED of the University Hospital Basel, Switzerland,
      during 2004-2013 were retrospectively reviewed. Follow-up in terms of the
      survival of these patients was performed through hospital databases, and direct
      contact with patients and caregivers. The primary endpoint was in hospital
      mortality and mortality within 10, 30, and 90 days, respectively. For our
      secondary endpoint, we investigated patient charts for the occurrence of
      dysrhythmias and laboratory findings. RESULTS: During the study period, a total
      of 240 patients were identified. Twelve patients were lost to follow-up. Initial
      ECG was performed in 234 (97.5%) patients and 149 (62.1%) patients received
      cardiac monitoring. During the time of monitoring, four dysrhythmias (sinus
      bradycardia, two ventricular premature beats, and atrial fibrillation) were
      observed. All patients survived, and no potential late serious dysrhythmia
      requiring a medical intervention was recorded. CONCLUSION: No cardiac
      complications occurred during ED stay or during the 90-day follow-up period.
      Therefore, the need for continued cardiac monitoring after electrical injury is
      not supported by our data.

PMID- 25969346
TI  - Weaker compressions after night shift? The WeCAN manikin study.
AB  - To assess whether the quality of chest compressions (CC) differs before and after
      a night shift. We carried out a cluster randomized study in three Emergency
      Departments and three ICUs in Paris, France. Physicians were assessed on a
      control day and immediately following after a night shift. The primary endpoint
      was the proportion of CC with a depth greater than 50 mm. We analyzed 67
      participants. The proportion of CC with a depth greater than 50 mm was similar on
      a control day and after a night shift [52% in both groups, mean difference of 0
      (95% confidence interval: -17 to 17)]. Other indicators of CC quality were
      unchanged after a night shift, except for the mean depth of CC (51 vs. 48 mm,
      P=0.01). We report in our sample that the quality of CC after a night shift is
      not inferior to a control day.

PMID- 25969348
TI  - Measuring disability of women with systemic sclerosis: validation of the italian
      version of the systemic sclerosis questionnaire.
AB  - BACKGROUND: The aim of this study was to validate the Italian version of Systemic
      Sclerosis Questionnaire (SySQ) and to evaluate its psychometric characteristics
      on a sample of inpatient and outpatient women with systemic sclerosis (SSc).
      METHODS: Internal and external validity of the Italian version of SySQ were
      analyzed. Internal validity included: 1) construct validity by means of factor
      analysis; 2) internal consistency for each category of SySQ through Cronbach's
      alpha; and 3) reproducibility over time with test-retest using both Pearson's
      correlation and Intraclass Correlation Coefficient. External validity included:
      1) concurrent validity, i.e. correlation with Skindex-17; and 2) discriminant
      validity, through comparison of scores for different groups of patients. RESULTS:
      We obtained data on 115 patients with SSc: 68 had the limited clinical form
      (lSSc) and 47 had the diffuse clinical form (dSSc). The structure of SySQ was
      confirmed by factor analysis. The questionnaire showed optimal internal
      consistency for all SySQ categories (Cronbach's alpha >0.84) and very good
      reproducibility over time (0.79-0.93, P<0.001). Regarding external validity, SySQ
      showed good correlation with Skindex-17 (P<0.01) and a satisfactory power of
      discrimination between groups affected by different clinical conditions.
      CONCLUSIONS: The study confirmed that the SySQ maintains good psychometric
      properties also in a language different from the original. It is a disease
      specific tool that can be routinely used in clinical practice for the evaluation
      of the level of disability in patients with SSc.

PMID- 25969349
TI  - Long-term safety of fertility sparing surgery in early stage ovarian cancer:
      comparison to standard radical surgical procedures.
AB  - OBJECTIVE: Fertility-sparing surgery (FSS) is a strategy often considered in
      young patients with low-grade (G1-2) early-stage epithelial ovarian cancer
      (eEOC), while is still controversial in high-risk patients. We investigated the
      role of FSS in low and high-risk eEOC patients undergoing comprehensive surgical
      staging. METHODS: We analyzed data from patients operated for an eEOC from 1975
      to 2011, focusing on patients submitted to FSS. Seventy patients out of 307 with
      eEOC were identified. Patients underwent FSS were compared with 237 patients
      underwent radical-comprehensive-staging (RCS) in the same period. Disease free
      (DFS) and overall (OS) survivals were evaluated using Kaplan-Meier and Cox
      models. RESULTS: Overall, 307 patients had surgery for eEOC: 70 (22.8%) and 237
      (77.2%) women had FSS and RCS, respectively. At univariate analysis, the
      execution of FSS not influenced DFS (HR:1.06 (95%CI: 0.56,2.02); p=0.84) and OS
      (HR:1.94 (95%CI: 0.75,4.98); p=0.16). Stage of disease was the only factor
      correlating with DFS (HR:4.73; 95%CI: 2.01,11.11; p<0.001). Independently,
      increased age (HR per 1-unit of age:1.06 (95%CI: 1.03,1.11); p<0.001) and high
      risk disease (HR:3.26; 95%CI: 1.23,8.62; p=0.01) remained associated with worse
      OS. Focusing on the high risk group (stage IAG3 or more) we observed that type of
      surgery (FSS v. RCS) did not influence DFS (p=0.77, log-rank test) and OS
      (p=0.08, log-rank test). CONCLUSIONS: FSS upholds oncologic effectiveness of RCS,
      preserving reproductive and endocrine functions. FSS does not increase risk of
      recurrence among high risk eEOC patients. Further prospective studies on this
      issue are warranted to improve patients' care.

PMID- 25969347
TI  - p38alpha MAPK is required for arsenic-induced cell transformation.
AB  - Arsenic exposure has been reported to cause neoplastic transformation through the
      activation of PcG proteins. In the present study, we show that activation of
      p38alpha mitogen-activated protein kinase (MAPK) is required for arsenic-induced
      neoplastic transformation. Exposure of cells to 0.5 MUM arsenic increased CRE and
      c-Fos promoter activities that were accompanied by increases in p38alpha MAPK and
      CREB phosphorylation and expression levels concurrently with AP-1 activation.
      Introduction of short hairpin (sh) RNA-p38alpha into BALB/c 3T3 cells markedly
      suppressed arsenic-induced colony formation compared with wildtype cells. CREB
      phosphorylation and AP-1 activation were decreased in p38alpha knockdown cells
      after arsenic treatment. Arsenic-induced AP-1 activation, measured as c-Fos and
      CRE promoter activities, and CREB phosphorylation were attenuated by p38
      inhibition in BALB/c 3T3 cells. Thus, p38alpha MAPK activation is required for
      arsenic-induced neoplastic transformation mediated through CREB phosphorylation
      and AP-1 activation.

PMID- 25969350
TI  - The impact of pleural disease on the management of advanced ovarian cancer.
AB  - Malignant pleural effusion is the most common site of stage IV ovarian cancer. A
      positive cytology is required for a stage IVA diagnosis. Unfortunately, the
      accuracy rate of pleural cytology remains low. A number of factors have been
      identified as prognostic for clinical outcomes in patients with epithelial
      ovarian cancer (EOC), the International Federation of Gynaecology and Obstetrics
      (FIGO) stage and residual tumor after debulking surgery being the most widely
      reported. Thereby careful selection of patients is crucially important, yet no
      preoperative predictor has proven sufficiently reliable to predict surgical
      outcome. The authors present a review of the literature on stage IV ovarian
      cancer specifically focusing on prognostic value of FIGO stage, preoperative
      workup, role of video-assisted thoracic surgery and maximal cytoreductive
      surgery. 

PMID- 25969351
TI  - Changing presentation of complete hydatidiform mole at the New England
      Trophoblastic Disease Center over the past three decades: does early diagnosis
      alter risk for gestational trophoblastic neoplasia?
AB  - OBJECTIVE: To compare the clinical presentation and incidence of postmolar
      gestational trophoblastic neoplasia (GTN) among recent (1994-2013) and historical
      (1988-1993) cases of complete hydatidiform mole (CHM). METHODS: This study
      included two non-concurrent cohorts (1988-1993 versus 1994-2013) of patients from
      the New England Trophoblastic Disease Center (NETDC). Clinical and pathologic
      reports of patients diagnosed with CHM between 1994 and 2013 were reviewed.
      Gestational age at evacuation, features of clinical presentation, human chorionic
      gonadotropin (hCG) levels, and the rate of progression to GTN were compared.
      RESULTS: In the current cohort (1994 to 2013) the median gestational age at
      diagnosis continued to decline compared to our prior cohort (1988-1993) (9weeks
      versus 12weeks). Patients from the current cohort were significantly more likely
      to be diagnosed prior to the 11th week of gestation (56 versus 41%, p=0.04).
      Patients in the current cohort were also significantly less likely to present
      with vaginal bleeding (46 versus 84%, p<0.001). Earlier diagnosis of complete
      mole did not result in a decrease in the rate of postmolar GTN. The frequencies
      of postmolar GTN in the current (1994-2013) and prior (1988-1993) cohorts were 19
      and 23%, respectively. In the current cohort, even diagnosis prior to ten weeks
      gestation did not decrease the risk of developing GTN. CONCLUSIONS: This study
      indicates that complete mole continues to be diagnosed progressively earlier
      resulting in a further decrease in some classical presenting symptoms. However,
      despite earlier detection, the risk of development of postmolar GTN has not been
      affected.

PMID- 25969352
TI  - Iridium-catalyzed enantioselective allylic alkylation with functionalized
      organozinc bromides.
AB  - Iridium-catalyzed enantioselective allylic alkylation of branched racemic
      carbonates with functionalized alkylzinc bromide reagents is described. Enabled
      by a chiral Ir/(P,olefin) complex, the method described allows allylic
      substitution with various primary and secondary alkyl nucleophiles with excellent
      regio- and enantioselectivities. The developed reaction was showcased in a
      concise, asymmetric synthesis of (-)-preclamol. 

PMID- 25969353
TI  - A novel method for expression and purification of authentic amyloid-beta with and
      without (15)N labels.
AB  - Amyloid-beta (Abeta) is a major constituent in the senile plaques of patients
      with Alzheimer's disease (AD). Abeta has been intensively studied in amyloid
      research; however, challenges posed by data reproducibility arise from purity of
      synthetic Abeta and high expense for its isotope-labeling. The difficulties
      motivate development and optimization of recombinant Abeta (rAbeta) production.
      Here, we report a new procedure to express and purify high quality rAbeta40 from
      Escherichia coli. The new Abeta construct expressed insoluble Abeta fused with an
      N-terminal histidine-tag connected by a linker harboring TEV protease cut site.
      After purification and partial refolding, the fusion tag was removed by TEV
      protease cleavage, immobilized metal affinity chromatography (IMAC), and reversed
      phase-HPLC purification with a yield of 3.5 mg/L culture with and without (15)N
      label. The rAbeta adopts classic amyloid fibrillization and is capable of binding
      to its clinical relevant metal ions.

PMID- 25969355
TI  - Anomalous lattice vibrations of monolayer MoS2 probed by ultraviolet Raman
      scattering.
AB  - We present a comprehensive Raman scattering study of monolayer MoS2 with
      increasing laser excitation energies ranging from the near-infrared to the deep
      ultraviolet. The Raman scattering intensities from the second-order phonon modes
      are revealed to be enhanced anomalously by only the ultraviolet excitation
      wavelength 354 nm. We demonstrate theoretically that such resonant behavior
      arises from a strong optical absorption that forms near the Gamma point and
      1/2GammaK of the band structure and an inter-valley resonant electronic
      scattering by the M-point phonons. These results advance our understanding of the
      double resonance Raman scattering process in low-dimensional semiconducting
      nanomaterials and provide a foundation for the technological development of
      monolayer MoS2 in the ultraviolet frequency range.

PMID- 25969354
TI  - Histochemical evidence of zoledronate inhibiting c-src expression and interfering
      with CD44/OPN-mediated osteoclast adhesion in the tibiae of mice.
AB  - The purpose of this study was to investigate the effect of zoledronate (ZA) on
      osteoclast functions and viability in the tibiae of 8-week-old male mice. After
      weekly intravenous administration of ZA (125 MUg/kg body weight) for 8 weeks, the
      mice were fixed by transcardial perfusion of 4% paraformaldehyde under
      anesthesia, and their tibiae were extracted for histochemical analysis. Compared
      with the control group, many tartrate-resistant acidic phosphatase-positive
      osteoclasts were found on the surface of the trabecular bone, but cartilage cores
      were obviously increased in the metaphysis of the ZA group. Osteoclasts of both
      groups showed similar expression of cathepsin K and matrix metalloproteinase-9.
      However, hardly any expression of c-src, a gene necessary for ruffled border
      formation and bone resorption, was found in osteoclasts of the ZA group.
      Moreover, no expression of CD44 or osteopontin (OPN) was observed in osteoclasts
      of the ZA group. Taken together, our findings suggest that ZA administration
      decreases the bone resorption ability of osteoclasts by inhibiting c-src
      expression and suppressing osteoclast adhesion by interfering with CD44/OPN
      binding.

PMID- 25969356
TI  - Asthma on the job.

PMID- 25969357
TI  - alpha1-antitrypsin: a polyfunctional protein?

PMID- 25969359
TI  - Progress and challenges for respiratory health in Brazil.

PMID- 25969360
TI  - Epinephrine: a short history.

PMID- 25969361
TI  - Protecting and monitoring the health of emergency responders.

PMID- 25969362
TI  - Tiotropium in asthma.

PMID- 25969363
TI  - Tiotropium in asthma - Authors' reply.

PMID- 25969364
TI  - Techniques to Reduce the Placebo Effect in Glaucoma Clinical Trials.
AB  - AIM: To evaluate techniques used to reduce the placebo effect in prior well
      controlled, single or double-masked placebo-controlled glaucoma trials. METHODS:
      This study was a retrospective, non-patient-based, observational review of phase
      I-III trials with a placebo arm for glaucoma medicines available after 1977.
      RESULTS: This study included 20 articles with 20 placebo control arms consisting
      of 458 patients evaluating 10 different glaucoma medications with 58 treatment
      arms. There was no statistical difference across the evaluated types of study
      designs to limit the placebo effect either for the morning trough or diurnal
      curve. The average reduction of the intraocular pressure in the placebo groups
      was 1.6 +/- 1.5 mm Hg for the morning trough and 1.3 +/- 1.3 mm Hg for the
      diurnal curve across all studies. CONCLUSION: The results of this study suggest
      that current design techniques described in the literature to limit the placebo
      effect appear ineffective compared to no additional techniques.

PMID- 25969365
TI  - Effect of helix length on the stability of the Lac repressor antiparallel coiled
      coil.
AB  - The helix length dependence of the stability of antiparallel four-chain coiled
      coils is investigated using eight synthetic peptides (Lac21-Lac28) whose
      sequences are derived from the tetramerization domain of the Lac repressor
      protein. Previous studies using analytical ultracentrifugation sedimentation
      equilibrium experiments to characterize Lac21 and Lac28 justifies the use of a
      two state model to describe the unfolding behavior of these two peptides. Using
      circular dichroism spectropolarimetry as a measure of tetramer assembly, both
      chemical and thermal denaturation experiments were carried out to determine
      thermodynamic parameters. We found that the hydrophobic core residues provide the
      greatest impact on stability and, as a consequence, must reorganize the register
      of the antiparallel helices to accommodate the burial of the nonpolar amino
      acids. Addition of noncore residues appears to have only a minor effect on
      stability, and in some cases, show a slight destabilization.

PMID- 25969367
TI  - IgE and risk of cancer in 37 747 individuals from the general population.
AB  - BACKGROUND: Immunoglobulin E (IgE) is produced by plasma cells, often as part of
      an allergic immune response. It is currently unknown whether plasma IgE levels
      are associated with risk of cancer in individuals from the general population. We
      tested the hypothesis that high levels of plasma total IgE are associated with
      overall risk of cancer and with risk of specific cancers. MATERIALS AND METHODS:
      Plasma total IgE was measured in 37 747 individuals from the general population,
      and the participants were followed prospectively for up to 30 years. All
      statistical tests were two-sided. RESULTS: During a mean follow-up of 7 years, a
      first cancer was diagnosed in 3454 participants. The multivariable adjusted
      hazard ratio for a 10-fold higher level of IgE was 1.05 [95% confidence interval
      (CI) 1.00-1.11; P = 0.04] for any cancer, 0.44 (0.30-0.64; P = 0.00002) for
      chronic lymphocytic leukemia (CLL), 0.53 (0.33-0.84; P = 0.007) for multiple
      myeloma, 1.54 (1.04-2.29; P = 0.03) for other non-Hodgkin lymphoma, 1.38 (1.04
      1.84; P = 0.03) for cancer of the oral cavity and pharynx, and 1.12 (1.00-1.25; P
      = 0.05) for lung cancer. The findings for CLL and multiple myeloma were generally
      robust; however, after correcting for 27 multiple comparisons only the finding
      for CLL remained significant. CONCLUSION: High levels of plasma total IgE were
      associated with low risk of CLL and possibly of multiple myeloma, without
      convincing evidence for high risk of any cancer type.

PMID- 25969366
TI  - Gluteal Tendinopathy: A Review of Mechanisms, Assessment and Management.
AB  - Tendinopathy of the gluteus medius and gluteus minimus tendons is now recognized
      as a primary local source of lateral hip pain. The condition mostly occurs in mid
      life both in athletes and in subjects who do not regularly exercise. Females are
      afflicted more than males. This condition interferes with sleep (side lying) and
      common weight-bearing tasks, which makes it a debilitating musculoskeletal
      condition with a significant impact. Mechanical loading drives the biological
      processes within a tendon and determines its structural form and load-bearing
      capacity. The combination of excessive compression and high tensile loads within
      tendons are thought to be most damaging. The available evidence suggests that
      joint position (particularly excessive hip adduction), together with muscle and
      bone elements, are key factors in gluteal tendinopathy. These factors provide a
      basis for a clinical reasoning process in the assessment and management of a
      patient presenting with localized lateral hip pain from gluteal tendinopathy.
      Currently, there is a lack of consensus as to which clinical examination tests
      provide best diagnostic utility. On the basis of the few diagnostic utility
      studies and the current understanding of the pathomechanics of gluteal
      tendinopathy, we propose that a battery of clinical tests utilizing a combination
      of provocative compressive and tensile loads is currently best practice in its
      assessment. Management of this condition commonly involves corticosteroid
      injection, exercise or shock wave therapy, with surgery reserved for recalcitrant
      cases. There is a dearth of evidence for any treatments, so the approach we
      recommend involves managing the load on the tendons through exercise and
      education on the underlying pathomechanics. 

PMID- 25969369
TI  - Liquid biopsies to evaluate early therapeutic response in colorectal cancer.

PMID- 25969368
TI  - High-throughput somatic mutation profiling in pulmonary sarcomatoid carcinomas
      using the LungCartaTM Panel: exploring therapeutic targets.
AB  - BACKGROUND: Pulmonary sarcomatoid carcinomas (SC) are tumors characterized by
      poor prognosis and resistance to conventional platinum-based chemotherapy. This
      study sought to describe the mutational profile of SC using high-throughput
      genotyping technology. PATIENTS AND METHODS: We used mass spectrometry to test
      114 surgical biopsies from 81 patients with SC for 214 mutations affecting 26
      oncogenes and tumor suppressor genes. RESULTS: In total, 75 (92.6%) patients were
      smokers. Within the total 81 tumors, 67 distinct somatic alterations were
      identified, with 56 tumors (69.1%) harboring at least one mutation. The most
      frequent mutations were KRAS (27.2%), EGFR (22.2%), TP53 (22.2%), STK11 (7.4%),
      NOTCH1 (4.9%), NRAS (4.9%), and PI3KCA (4.9%). The EGFR mutations were almost
      always rare mutations (89%). In 32 tumors (39.5%), two or more mutations co
      existed, with up to four mutations in a single case. In six different cases,
      comparative genetic analysis of different histological areas from the same tumor
      (giant, spindle, or epithelial component) revealed a 61% concordance rate for all
      the mutations with a 10% detection threshold, compared with 91.7% with a 20%
      detection threshold. CONCLUSION: Our results demonstrated a high mutation rate
      and frequent co-mutations. Despite SC tumors exhibiting a high histological
      heterogeneity, some intratumoral molecular homogeneity was found. Now with newly
      developed targeted therapies, SC patients may be eligible for new target
      mutations, and can now therefore be screened for clinical trials.

PMID- 25969371
TI  - Heterogeneity of driver genes and therapeutic implications in colorectal cancer.

PMID- 25969372
TI  - Vitamin D Receptor Genotype Modulates the Correlation between Vitamin D and
      Circulating Levels of let-7a/b and Vitamin D Intake in an Elderly Cohort.
AB  - BACKGROUND AND AIMS: Circulating microRNAs (miRNAs) are linked to disease and are
      potential biomarkers. Vitamin D may modulate miRNA profiles, and vitamin D status
      has been linked to risk of disease, including cardiovascular disease and cancers.
      We hypothesise that genotypic variance influences these relationships. We
      examined the correlations between vitamin D intake and circulating levels of the
      miRNAs let-7a/b, and the involvement of two common vitamin D receptor (VDR)
      polymorphisms, BsmI and ApaI. METHODS: Two hundred participants completed food
      frequency and supplement questionnaires, and were assayed for circulating let-7b
      expression by qPCR. Polymorphisms were detected using restriction fragment length
      polymorphism-PCR. RESULTS: let-7b expression negatively correlated with vitamin D
      intake (rs=-0.20, p=0.005). The magnitude and direction of correlation were
      maintained in the presence of the BsmI restriction site (rs=-0.27, p=0.0005).
      However, in the absence of BsmI restriction site, the direction of the
      correlation was reversed (rs=+0.319, p=0.0497). These correlations were
      significantly different (z-score=2.64, p=0.0085). The correlation between vitamin
      D intake and let-7a was only significant in those without the ApaI restriction
      site. CONCLUSIONS: The correlation between vitamin D intake and let-7a/b
      expression in this cohort varies with VDR genotype. This study highlights the
      importance of considering underlying genotypic variance in miRNA expression
      studies and in nutritional epigenetics generally.

PMID- 25969370
TI  - Impact of perioperative chemotherapy on survival in patients with advanced
      primary urethral cancer: results of the international collaboration on primary
      urethral carcinoma.
AB  - BACKGROUND: To investigate the impact of perioperative chemo(radio)therapy in
      advanced primary urethral carcinoma (PUC). PATIENTS AND METHODS: A series of 124
      patients (86 men, 38 women) were diagnosed with and underwent surgery for PUC in
      10 referral centers between 1993 and 2012. Kaplan-Meier analysis with log-rank
      testing was used to investigate the impact of perioperative chemo(radio)therapy
      on overall survival (OS). The median follow-up was 21 months (mean: 32 months;
      interquartile range: 5-48). RESULTS: Neoadjuvant chemotherapy (NAC), neoadjuvant
      chemoradiotherapy (N-CRT) plus adjuvant chemotherapy (ACH), and ACH was delivered
      in 12 (31%), 6 (15%) and 21 (54%) of these patients, respectively. Receipt of
      NAC/N-CRT was associated with clinically node-positive disease (cN+; P = 0.033)
      and lower utilization of cystectomy at surgery (P = 0.015). The objective
      response rate to NAC and N-CRT was 25% and 33%, respectively. The 3-year OS for
      patients with objective response to neoadjuvant treatment (complete/partial
      response) was 100% and 58.3% for those with stable or progressive disease (P =
      0.30). Of the 26 patients staged >=cT3 and/or cN+ disease, 16 (62%) received
      perioperative chemo(radio)therapy and 10 upfront surgery without perioperative
      chemotherapy (38%). The 3-year OS for this locally advanced subset of patients
      (>=cT3 and/or cN+) who received NAC (N = 5), N-CRT (N = 3), surgery-only (N = 10)
      and surgery plus ACH (N = 8) was 100%, 100%, 50% and 20%, respectively (P =
      0.016). Among these 26 patients, receipt of neoadjuvant treatment was
      significantly associated with improved 3-year relapse-free survival (RFS) (P =
      0.022) and OS (P = 0.022). Proximal tumor location correlated with inferior 3
      year RFS and OS (P = 0.056/0.005). CONCLUSION: In this series, patients who
      received NAC/N-CRT for cT3 and/or cN+ PUC appeared to demonstrate improved
      survival compared with those who underwent upfront surgery with or without ACH.

PMID- 25969374
TI  - Measurements in Pediatric Patients with Cardiomyopathies: Comparison of Cardiac
      Magnetic Resonance Imaging and Echocardiography.
AB  - AIMS: Cardiomyopathies are common cardiovascular diseases in children. Cardiac
      magnetic resonance imaging (cMRI) and echocardiography (Echo) are routinely
      applied in the detection and diagnosis of pediatric cardiomyopathies. In this
      study, we compared and explored the correlation between these two measurements in
      pediatric patients with various cardiomyopathies. METHODS AND RESULTS: A total of
      53 pediatric patients with cardiomyopathy hospitalized during the recent 3 years
      in our hospital were analyzed. All of them and 22 normal controls were assessed
      by both cMRI and Echo. Cardiac function of the patients was graded according to
      the New York Heart Association functional classification. The cardiac function
      indexes measured with both cMRI and Echo included left-ventricular (LV) end
      diastolic volume (EDV), end-systolic volume, ejection fraction and fractional
      shortening. These parameters were somehow lower in cMRI measurements than in Echo
      measurements. The index of diastolic function, such as peak filling rate (PFR)
      measured with cMRI, had a good correlation with the clinical cardiac functional
      score, while the index of the diastolic function (early/atrial filling ratio and
      isovolumic relaxation time) measured with Echo was not well correlated with the
      clinical cardiac function score. Significant systolic dysfunction was detected by
      cMRI in 34 patients with dilated cardiomyopathy, LV noncompaction or endocardial
      fibroelastosis. Significant diastolic dysfunction was detected by cMRI in 19
      patients with hypertrophic cardiomyopathy or restrictive cardiomyopathy showing
      an alteration in PFR and EDV. CONCLUSION: Both cMRI and Echo are of great value
      in the diagnosis and assessment of cardiac function in pediatric patients with
      cardiomyopathy. cMRI could accurately display the characteristic morphological
      changes in the hearts affected with cardiomyopathies, and late gadolinium
      enhancement on cMRI may reveal myocardial fibrosis, which has obvious advantages
      over Echo measurements in diagnosis. Furthermore, cMRI can quantitatively
      determine ventricular function because it does not make invalid geometrical
      assumptions.

PMID- 25969373
TI  - Expectations of barriers to psychosocial care: views of parents and adolescents
      in the community.
AB  - Parents with a child suffering from psychosocial problems frequently experience
      barriers to psychosocial care, which may hinder access. Expectations of barriers
      may have the same effect, but evidence is lacking. The aim of this study is to
      examine parents' and adolescents' expectations of barriers regarding psychosocial
      care for the child, along with associated child and family characteristics. We
      obtained data on an age-stratified random sample of school children/pupils aged 4
      18 via questionnaires (N = 666; response rate 70.3 %). Expectations of barriers
      to psychosocial care were measured with the "Barriers to Treatment Participation
      Scale-Expectancies" questionnaire (BTPS-exp). Results showed that 64 % of the
      parents of children below age 12, 59 % of the parents of adolescents (age 12-18),
      and 84 % of the adolescents expected one or more barriers. Parents and
      adolescents expected barriers most frequently with respect to irrelevance of
      treatment. Mainly parents with low educational level and their adolescents
      expected barriers regarding treatment, and quite a few characteristics of parents
      of adolescents were associated with expecting multiple barriers regarding
      treatment demands and issues, for example, single parents, parents of lower
      educational level and of adolescent boys, and parents of adolescents with
      psychosocial problems. We conclude that adolescents especially, but also their
      parents and parents of younger children, expect major barriers to psychosocial
      care, which may greatly hinder appropriate care seeking. This evidence may
      support professionals and policymakers in their attempts to improve access to
      psychosocial care.

PMID- 25969375
TI  - Detection of Copper (II) and Cadmium (II) binding to dissolved organic matter
      from macrophyte decomposition by fluorescence excitation-emission matrix spectra
      combined with parallel factor analysis.
AB  - Fluorescence excitation-emission matrix (EEM) spectra coupled with parallel
      factor analysis (PARAFAC) was used to characterize dissolved organic matter (DOM)
      derived from macrophyte decomposition, and to study its complexation with Cu (II)
      and Cd (II). Both the protein-like and the humic-like components showed a marked
      quenching effect by Cu (II). Negligible quenching effects were found for Cd (II)
      by components 1, 5 and 6. The stability constants and the fraction of the binding
      fluorophores for humic-like components and Cu (II) can be influenced by
      macrophyte decomposition of various weight gradients in aquatic plants.
      Macrophyte decomposition within the scope of the appropriate aquatic phytomass
      can maximize the stability constant of DOM-metal complexes. A large amount of
      organic matter was introduced into the aquatic environment by macrophyte
      decomposition, suggesting that the potential risk of DOM as a carrier of heavy
      metal contamination in macrophytic lakes should not be ignored. 

PMID- 25969376
TI  - Atmospheric pollution history at Linfen (China) uncovered by magnetic and
      chemical parameters of sediments from a water reservoir.
AB  - We studied magnetic and chemical parameters of sediments from sediments of a
      water reservoir at Linfen (China) in order to quantitatively reconstruct the
      atmospheric pollution history in this region. The results show that the main
      magnetic phases are magnetite and maghemite originating from the surrounding
      catchment and from anthropogenic activities, and there is a significant positive
      relationship between magnetic concentration parameters and heavy metals
      concentrations, indicating that magnetic proxies can be used to monitor the
      anthropogenic pollution. In order to uncover the atmospheric pollution history,
      we combined the known events of environmental improvement with variations of
      magnetic susceptibility (chi) and heavy metals along the cores to obtain a
      detailed chronological framework. In addition, air comprehensive pollution index
      (ACPI) was reconstructed from regression equation among magnetic and chemical
      parameters as well as atmospheric monitoring data. Based on these results, the
      atmospheric pollution history was successfully reconstructed. 

PMID- 25969377
TI  - The spatiotemporal distributions and determinants of ambient fungal spores in the
      Greater Taipei area.
AB  - Airborne fungal spores, a type of bioaerosols, are significant air pollutants. We
      conducted a study to determine the spatiotemporal distributions of ambient fungi
      in the Greater Taipei area and develop land use regression (LUR) models for total
      and major fungal taxa. Four seasonal sampling campaigns were conducted over a
      year at 44 representative sites. Multiple regressions were performed to construct
      the LUR models. Ascospores were the most prevalent category, followed by
      Aspergillus/Penicillium, basidiospores, and Cladosporium. The highest fungal
      concentrations were found in spring. According to the LUR models, higher
      concentrations of Aspergillus/Penicillium and basidiospores were respectively
      present in residential/commercial areas and in areas with shorter road lengths.
      Various meteorological factors, particulates with aerodynamic diameters of <=10
      MUm, and elevation also had significant relationships with fungal concentrations.
      The LUR models developed in this study can be used to assess spatiotemporal
      fungal distribution in the Greater Taipei area. 

PMID- 25969378
TI  - Microevolution due to pollution in amphibians: A review on the genetic erosion
      hypothesis.
AB  - The loss of genetic diversity, due to exposure to chemical contamination (genetic
      erosion), is a major threat to population viability. Genetic erosion is the loss
      of genetic variation: the loss of alleles determining the value of a specific
      trait or set of traits. Almost a third of the known amphibian species is
      considered to be endangered and a decrease of genetic variability can push them
      to the verge of extinction. This review indicates that loss of genetic variation
      due to chemical contamination has effects on: 1) fitness, 2) environmental
      plasticity, 3) co-tolerance mechanisms, 4) trade-off mechanisms, and 5) tolerance
      to pathogens in amphibian populations.